PMID- 29197139
TI  - The impact of silver nanoparticles integration on biofilm formation and
      mechanical properties of glass ionomer cement.
AB  - OBJECTIVES: To study the effect of silver nanoparticles incorporation to glass
      ionomer cement (GIC) on the Staphylococcus aureus biofilm in terms of bacterial
      growth and evaluate the incorporating effect on hardness and compressive
      strength. METHODS: Silver nanopowder was added in concentration 0, 1, 3, and 5
      wt% to the conventional powder of GIC Fuji IX GP and then the powder is added to
      the liquid and mixed together with the recommended Powder/liquid ratio of 3.6:1
      g. One hundred and twenty disc and cylindrical-shaped specimens were prepared
      using teflon molds. The specimens were put in tissue culture plate wells
      contained S. aureus in brain-heart infusion broth. The plate was incubated at 37
      degrees C for 24 h. Specimens were then washed, fixed, dehydrated, and air dried.
      The spatial distribution of biofilm was examined via scanning electron
      microscope. The minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) were also evaluated. After setting, the specimens were stored
      in distilled water for 24 h before testing for microhardness and compressive
      strength. RESULTS: Scanning electron photomicrographs of biofilm formed on the
      control GIC, showed a consistent biofilm with a thick sheet of cells, whereas
      those formed were less dense at 3 wt% and below the detection limit at 5 wt%
      silver nanoparticles. MIC and MBC of S. aureus were 25 and 50 ug/mL,
      respectively. The microhardness and compressive strength values of tested groups
      showed a nonsignificant decrease from the control group, P = .58 and .82,
      respectively. CONCLUSION: Incorporation of silver nanoparticles with GIC can
      limit S. aureus biofilm formation with an insignificant effect on mechanical
      properties and noticeable influence on its coloration, which restrict its usage
      in areas where esthetic is not of major concern. CLINICAL SIGNIFICANCE: As the
      modification of GIC with silver nanoparticles improved the antibiofilm properties
      without altering its mechanical properties, it could be used as a restoration of
      root carious lesion mainly in nonesthetic areas, a base under composite
      restorations in deep posterior cavities and as a core material in caries
      susceptible patients.

PMID- 29197140
TI  - The effect of interferon-free regimens on health-related quality of life in East
      Asian patients with chronic hepatitis C.
AB  - BACKGROUND: Interferon (IFN)-based regimens cause significant impairment of
      health-related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN-free
      regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV
      patients is unclear due to lack of published evidence. AIM: To assess HRQL in
      East Asian HCV patients treated with an IFN-free regimen with
      sofosbuvir+ribavirin. METHODS: Patients completed Short Form-36 (SF-36) before,
      during and after treatment. RESULTS: 686 subjects were included (China: 56.7%; S.
      Korea: 18.8%; Taiwan: 12.7%; genotype 2: 40.8%; genotype 1: 29.6%; genotype 3:
      18.4%; genotype 6: 11.2%; cirrhosis: 13.4%; treatment-naive: 66.5%). Patients
      received either pegylated-IFN, sofosbuvir, and ribavirin (IFN+SOF+RBV) for 12
      weeks (n = 155, genotypes 1 and 6) or SOF+RBV for 12-24 weeks (n = 531, all
      genotypes). The SVR-12 rates were 95.5% and 96.0%; respectively (P = .76).
      Baseline HRQL scores were similar between treatment groups (all P > .05). By the
      end of treatment, the IFN-treated group experienced significant declines in most
      HRQL scores (on average, by up to -13.3 points on a 0-100 scale from the baseline
      level, P < .02) while subjects on SOF/RBV had milder impairments (up to -5.4
      points). Achieving SVR-12 was associated with HRQL improvement regardless of
      regimen (up to +2.9 points, P < .05). The use of IFN-free treatment was a
      consistent independent predictor of higher HRQL scores during treatment (beta:
      +2.1 to +10.7 points, P < .02). CONCLUSIONS: East Asian HCV patients treated with
      an IFN-free regimen had better on-treatment HRQL scores. These data should inform
      policymakers about the comprehensive benefits of IFN-free regimens in East Asian
      patients with HCV.

PMID- 29197142
TI  - New insights on plant phenological response to temperature revealed from long
      term widespread observations in China.
AB  - Constraints of temperature on spring plant phenology are closely related to plant
      growth, vegetation dynamics, and ecosystem carbon cycle. However, the effects of
      temperature on leaf onset, especially for winter chilling, are still not well
      understood. Using long-term, widespread in situ phenology observations collected
      over China for multiple plant species, this study analyzes the quantitative
      response of leaf onset to temperature, and compares empirical findings with
      existing theories and modeling approaches, as implemented in 18 phenology
      algorithms. Results show that the growing degree days (GDD) required for leaf
      onset vary distinctly among plant species and geographical locations as well as
      at organizational levels (species and community), pointing to diverse adaptation
      strategies. Chilling durations (CHD) needed for releasing bud dormancy decline
      monotonously from cold to warm areas with very limited interspecies variations.
      Results also reveal that winter chilling is a crucial component of phenology
      models, and its effect is better captured with an index that accounts for the
      inhomogeneous effectiveness of low temperature to chilling rate than with the
      conventional CHD index. The impact of spring warming on leaf onset is nonlinear,
      better represented by a logistical function of temperature than by the linear
      function currently implemented in biosphere models. The optimized base
      temperatures for thermal accumulation and the optimal chilling temperatures are
      species-dependent and average at 6.9 and 0.2 degrees C, respectively. Overall,
      plants' chilling requirement is not a constant, and more chilling generally
      results in less requirement of thermal accumulation for leaf onset. Our results
      clearly demonstrate multiple deficiencies of the parameters (e.g., base
      temperature) and algorithms (e.g., method for calculating GDD) in conventional
      phenology models to represent leaf onset. Therefore, this study not only advances
      our mechanistic and quantitative understanding of temperature controls on leaf
      onset but also provides critical information for improving existing phenology
      models.

PMID- 29197141
TI  - The blood-brain barrier internalises Cryptococcus neoformans via the EphA2
      tyrosine kinase receptor.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen that causes life
      threatening meningitis most commonly in populations with impaired immunity. Here,
      we resolved the transcriptome of the human brain endothelium challenged with C.
      neoformans to establish whether C. neoformans invades the CNS by co-opting
      particular signalling pathways as a means to promote its own entry. Among the 5
      major pathways targeted by C. neoformans, the EPH-EphrinA1 (EphA2) tyrosine
      kinase receptor-signalling pathway was examined further. Silencing the EphA2
      receptor transcript in a human brain endothelial cell line or blocking EphA2
      activity with an antibody or chemical inhibitor prevented transmigration of C.
      neoformans in an in vitro model of the blood-brain barrier (BBB). In contrast,
      treating brain endothelial cells with an EphA2 chemical agonist or an EphA2
      ligand promoted greater migration of fungal cells across the BBB. C. neoformans
      activated the EPH-tyrosine kinase pathway through a CD44-dependent
      phosphorylation of EphA2, promoting clustering and internalisation of EphA2
      receptors. Moreover, HEK293T cells expressing EphA2 revealed an association
      between EphA2 and C. neoformans that boosted internalisation of C. neoformans.
      Collectively, the results suggest that C. neoformans promotes EphA2 activity via
      CD44, and this in turn creates a permeable barrier that facilitates the migration
      of C. neoformans across the BBB.

PMID- 29197143
TI  - Do mental health consumers want to improve their long-term disease risk
      behaviours? A survey of over 2000 psychiatric inpatients.
AB  - Policies and clinical guidelines acknowledge the role mental health services have
      in addressing the physical health of individuals with a mental illness; however,
      little research has explored interest in reducing health risk behaviours or the
      acceptability of receiving support to reduce such risks among psychiatric
      inpatients. This study estimated the prevalence of four long-term disease risk
      behaviours (tobacco smoking, hazardous alcohol consumption, inadequate fruit
      and/or vegetable consumption, and inadequate physical activity); patient interest
      in reducing these risks; and acceptability of being provided care to do so during
      a psychiatric inpatient stay. A cross-sectional survey was undertaken with 2075
      inpatients from four inpatient psychiatric facilities in one health district in
      Australia (October 2012-April 2014). Prevalence of risk behaviours ranged from
      50.2% (inadequate physical activity) to 94.8% (inadequate fruit and/or vegetable
      consumption). The majority of respondents (88.4%) had more than one risk
      behaviour, and most were seriously considering improving their risk behaviours
      (47.6% to 65.3%). The majority (80.4%) agreed that it would be acceptable to be
      provided support and advice to change such behaviours during their psychiatric
      inpatient stay. Some diagnoses were associated with smoking and hazardous alcohol
      consumption, interest in reducing alcohol consumption and increasing fruit and/or
      vegetable consumption, and acceptability of receiving advice and support. The
      findings reinforce the need and opportunity for psychiatric inpatient facilities
      to address the long-term disease risk behaviours of their patients.

PMID- 29197144
TI  - Protein Folding in the Presence of Water-Soluble Cyclic Diselenides with Novel
      Oxidoreductase and Isomerase Activities.
AB  - The protein disulfide isomerase (PDI) family, found in the endoplasmic reticulum
      (ER) of the eukaryotic cell, catalyzes the formation and cleavage of disulfide
      bonds and thereby helps in protein folding. A decrease in PDI activity under ER
      stress conditions leads to protein misfolding, which is responsible for the
      progression of various human diseases, such as Alzheimer's, Parkinson's, diabetes
      mellitus, and atherosclerosis. Here we report that water-soluble cyclic
      diselenides mimic the multifunctional activity of the PDI family by facilitating
      oxidative folding, disulfide formation/reduction, and repair of the scrambled
      disulfide bonds in misfolded proteins.

PMID- 29197145
TI  - Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after
      orthotopic liver transplantation.
AB  - BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA
      combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV
      recurrence after orthotopic liver transplantation (OLT). The need of ribavirin
      addition is under debate as anaemia and decreased renal function are prevalent in
      transplant cohorts. The aim of this study was thus to assess safety and long-term
      efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT.
      PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 +/-
      8.5 years [mean +/- SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55%
      [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free
      treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir
      (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and
      PrOD: 4%/7%. RESULTS: Data of at least 96 weeks of FUP after treatment cessation
      (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment
      response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a:
      11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%];
      GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late
      relapses occurred. In total, 16 severe adverse events occurred, including two
      newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients
      died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment
      free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1
      respectively). Reasons for death were: multi-organ failure (N = 4), impaired
      graft function (N = 1) and unknown (N = 1). CONCLUSION: RBV-free DAA combinations
      for the treatment of HCV recurrence after OLT are highly efficacious and well
      tolerated. Our long-term data show that viral eradication is durable but not
      necessarily translated into beneficial long-term clinical outcome.

PMID- 29197146
TI  - Is myocardial repolarization duration associated with repolarization
      heterogeneity?
AB  - BACKGROUND: Dispersion of repolarization is theorized as one mechanism by which
      myocardial repolarization prolongation causes lethal torsades de pointes, (TdP).
      Our primary purpose was to determine whether prolongation of myocardial
      repolarization as measured by the heart rate-corrected J-to-T peak interval
      (JTpkc), is associated with repolarization heterogeneity as measured by
      transmural dispersion, defined as the median duration from the peak to the end of
      the T wave (TpTe). METHODS: A retrospective cohort study was performed at a
      single urban tertiary ED from July 2011-September 2012. Inclusion criteria
      included all consecutive ED patients with ECG based on QTc and QRS intervals.
      Automated measurements of all intervals were performed. The association of JTpkc
      with the dependent variable TpTe was assessed after adjustment for QRS and RR
      interval durations with a multiple linear regression model. A secondary analysis
      included a similar adjusted assessment of the association of JTpkc with QT
      dispersion, QTd. Finally, we constructed two multiple regression models to assess
      the association of clinical causative factors of TdP with TpTe and JTpkc.
      RESULTS: Eight hundred seventy-four cases were included: 186 with QTc <500 ms,
      118 with QTc >=500 and QRS >=120 ms, and 570 with QTc >=500 and QRS <120 ms. The
      coefficient for association of JTpkc with TpTe was -0.10 (95%CI -0.15 to -0.05),
      and for JTpkc with QTd was 0.03 (95% CI -0.01 to 0.06). Clinical causative TdP
      factors were associated more with JTpkc than TpTe. CONCLUSION: Repolarization
      duration as measured by JTpkc is not positively associated with dispersion of
      repolarization as measured by TpTe or QTd. Dispersion of repolarization may not
      be a critical mechanistic link between QTc prolongation and TdP.

PMID- 29197147
TI  - Immune response to hepatitis B vaccine in patients with chronic hepatitis C
      infection: A systematic review and meta-analysis.
AB  - Hepatitis B virus and hepatitis C virus (HCV) co-infection can add to the
      severity of hepatitis and the risks of liver cirrhosis and hepatocellular
      carcinoma. Whether chronic HCV infection decreases antibody response to hepatitis
      B vaccination is still controversial. We evaluate the influence of HCV infection
      on antibody response to hepatitis B vaccination by a systematic review of
      published works with a meta-analysis of clinical trials. The random-effects model
      of DerSimonian and Laird with heterogeneity and sensitivity analyses were used in
      this study. The end-point of interest was the rate of patients showing
      seroconversion of antibody responses at completion of hepatitis B vaccination
      schedule among patients with chronic HCV infection versus healthy controls. We
      identified 11 studies involving 704 patients with HCV and 812 controls. Our
      results show a significant decrease in antibody seroconversion rates among
      patients with HCV versus healthy controls (pooled odds ratio = 0.17 [95%
      confidence interval, 0.11-0.28]). The P-value was 0.21 for our test of study
      heterogeneity. Stratified analysis in subgroups of interest and sensitivity
      analysis did not meaningfully change our results. Our meta-analysis showed
      patients with hepatitis C infection have a statistically significant lower rate
      of seroconversion in comparison to healthy controls, both in cirrhotic and non
      cirrhotic patients. Chronic HCV infection can decrease the immune response to a
      standard schedule of hepatitis B vaccination. Further studies are needed to
      investigate the optimum vaccination schedule for patients with chronic HCV
      infection.

PMID- 29197148
TI  - Decidual CD68+ HLA-DR+ CD163- M1 macrophages increase in miscarriages with normal
      fetal chromosome.
AB  - PROBLEM: Is an abnormal increase or decrease of M1/M2 macrophages observed in the
      deciduae of miscarriages with normal fetal chromosome (MN)? METHODS OF STUDY:
      Deciduae of 18 MN and 26 miscarriages with abnormal fetal chromosome (MA) were
      obtained. Additionally, deciduae from 15 women whose pregnancies ended in induced
      abortions (IA) and endometriums at the mid-luteal phase from 19 non-pregnant
      women endomeriums of mid-luteal phases (EM) were obtained. Macrophages were
      analyzed by flow cytometry using monoclonal antibodies for CD68, HLA-DR, and
      CD163. RESULTS: M1 macrophages, defined as CD68+ HLA-DR+ CD163- cells, increased
      in MN compared with MA or IA. M2 macrophages, defined as CD68+ HLA-DR- CD163+
      cells, increased in the deciduae of MA and IA compared with EM. However, this
      increase was not observed in the deciduae of MN. CONCLUSION: Our findings of
      phenotypic characters of decidual macrophages in MN provide additional evidence
      that M2 polarization is favorable for the maintenance of early stages of
      pregnancy.

PMID- 29197150
TI  - Insight into Metal-Organic Framework Reactivity: Chemical Water Oxidation
      Catalyzed by a [Ru(tpy)(dcbpy)(OH2 )]2+ -Modified UiO-67.
AB  - Investigation of chemical water oxidation was conducted on [Ru(tpy)(dcbpy)(OH2
      )]2+ (tpy=2,2':6',2''-terpyridine, dcbpy=5,5'-dicarboxy-2,2'-bipyridine)-doped
      UiO-67 metal-organic framework (MOF). The MOF catalyst exhibited a single-site
      reaction pathway with kinetic behavior similar to that of a homogeneous Ru
      complex. The reaction was first order with respect to both the concentration of
      the Ru catalyst and ceric ammonium nitrate (CAN), with kcat =3(+/-2)*10-3  m-1  s
      1 in HNO3 (pH 0.5). The common degradation pathways of ligand dissociation and
      dimerization were precluded by MOF incorporation, which led to sustained
      catalysis and greater reusability as opposed to the molecular catalyst in
      homogeneous solution. Lastly, at the same loading (ca. 97 nmol mg-1 ), samples of
      different particle sizes generated the same amount of oxygen (ca. 100 nmol),
      indicative of in-MOF reactivity. The results suggest that the rate of redox
      hopping charge transport is sufficient to promote chemistry throughout the MOF
      particulates.

PMID- 29197149
TI  - CD29 is highly expressed on epithelial, myoepithelial, and mesenchymal stromal
      cells of human salivary glands.
AB  - OBJECTIVE: The phenotype of the cells present in the ductal region of salivary
      glands has been well characterized. However, it is imperative to identify novel
      biomarkers that can identify different cell types present in other glandular
      components for the development of therapeutic strategies and diagnostics of
      salivary gland disorders and malignancies. Our study aimed at the
      characterization of the expression and distribution of various cell surface
      markers, especially with a focus on CD29 in human fetal as well as adult glands.
      MATERIALS AND METHODS: Paired human midgestation fetal and adult parotid,
      sublingual, and submandibular glands were collected. Phenotypic expression of
      various lineage-specific cell surface markers including CD29 was investigated in
      freshly collected glands. The findings were further corroborated by
      immunohistochemistry. RESULTS: Enriched expression of CD29 was found on acinar
      and ductal epithelial, mesenchymal stromal, and myoepithelial cells; CD29+ cells
      co-expressed epithelial (CD324, CD326, NKCC1, and CD44), mesenchymal (CD73, CD90,
      vimentin, and CD34), and myoepithelial (alpha-SMA) cell-specific progenitor
      markers in both fetal as well as adult salivary glands. CONCLUSION: CD29 is
      widely expressed in human salivary glands, and it could serve as a potential
      biomarker for devising novel cellular therapeutic and diagnostic strategies for
      salivary gland disorders and malignancies.

PMID- 29197151
TI  - Transcriptional regulation of CacyBP/SIP gene and the influence of increased
      CacyBP/SIP level on gene expression pattern in colorectal cancer HCT116 cells.
AB  - The CacyBP/SIP protein is expressed at a particularly high level in brain,
      spleen, and various tumors. In this work, we have studied transcriptional
      regulation of the CacyBP/SIP gene and the influence of increased CacyBP/SIP level
      on gene expression in colorectal cancer HCT116 cells. We have shown that E2F1,
      EGR1, and CREB transcription factors bind to the CacyBP/SIP gene promoter and
      stimulate transcription of CacyBP/SIP gene. The role of CREB was further
      confirmed by the observation that forskolin, a strong activator of CREB
      phosphorylation/activity, increased CacyBP/SIP gene promoter activity. Moreover,
      we have shown that CREB dominant negative mutants, CREB133 and KCREB, inhibits
      CacyBP/SIP promoter activity. To check the biological significance of increased
      CacyBP/SIP expression/level we have applied RNA microarray analysis and have
      found that upregulation of CacyBP/SIP entails changes in mRNA level of many genes
      involved, among others, in immune processes. (c) 2017 IUBMB Life, 70(1):50-59,
      2018.

PMID- 29197153
TI  - Recommendations for future research in relation to pediatric pulmonary embolism:
      communication from the SSC of the ISTH.

PMID- 29197152
TI  - The national burden of influenza-associated severe acute respiratory illness
      hospitalization in Rwanda, 2012-2014.
AB  - BACKGROUND: Estimates of influenza-associated hospitalization are severely
      limited in low- and middle-income countries, especially in Africa. OBJECTIVES: To
      estimate the national number of influenza-associated severe acute respiratory
      illness (SARI) hospitalization in Rwanda. METHODS: We multiplied the influenza
      virus detection rate from influenza surveillance conducted at 6 sentinel
      hospitals by the national number of respiratory hospitalization obtained from
      passive surveillance after adjusting for underreporting and reclassification of
      any respiratory hospitalizations as SARI during 2012-2014. The population at risk
      was obtained from projections of the 2012 census. Bootstrapping was used for the
      calculation of confidence intervals (CI) to account for the uncertainty
      associated with all levels of adjustment. Rates were expressed per 100 000
      population. A sensitivity analysis using a different estimation approach was also
      conducted. RESULTS: SARI cases accounted for 70.6% (9759/13 813) of respiratory
      admissions at selected hospitals: 77.2% (6783/8786) and 59.2% (2976/5028) among
      individuals aged <5 and >=5 years, respectively. Overall, among SARI cases
      tested, the influenza virus detection rate was 6.3% (190/3022): 5.7% (127/2220)
      and 7.8% (63/802) among individuals aged <5 and >=5 years, respectively. The
      estimated mean annual national number of influenza-associated SARI
      hospitalizations was 3663 (95% CI: 2930-4395-rate: 34.7; 95% CI: 25.4-47.7): 2637
      (95% CI: 2110-3164-rate: 168.7; 95% CI: 135.0-202.4) among children aged <5 years
      and 1026 (95% CI: 821-1231-rate: 11.3; 95% CI: 9.0-13.6) among individuals aged
      >=5 years. The estimates obtained from both approaches were not statistically
      different (overlapping CIs). CONCLUSIONS: The burden of influenza-associated SARI
      hospitalizations was substantial and was highest among children aged <5 years.

PMID- 29197154
TI  - Risk factors for serious outcomes associated with influenza illness in high-
      versus low- and middle-income countries: Systematic literature review and meta
      analysis.
AB  - AIM: To determine factors associated with a serious outcome (hospital admission
      or severe outcome: critical care or death) and associated with illness caused by
      laboratory-confirmed influenza, with a specific interest in low- and middle
      income countries (LMIC). METHOD: Databases were searched on 11 March 2016 for
      reports of influenza and factors associated with mortality or morbidity in
      humans, with no language restrictions. Pooled risks were estimated using random
      effects models. RESULTS: Despite the heterogeneity of results across studies,
      known risk factors for serious disease were associated with both hospital
      admission and severe outcomes (critical care and/or death). In LMIC, but not in
      high income countries (HIC), pregnant women, people with HIV/AIDS and children <
      5 years old (compared with older children) were at increased risk of a severe
      outcome. Also, although all patients with neurological conditions were at higher
      risk of severe outcomes than those without, children were at higher risk than
      adults and children who lived in a LMIC were at significantly higher risk than
      those living in HIC. Adults were more likely than children to suffer a severe
      outcome if they had diabetes or a hematologic condition, were obese or had liver
      disease. Asthma is a risk factor for hospital admission but not for severe
      outcomes. CONCLUSION: Known risk factors for serious disease remain important
      predictors of hospital admission and severe outcomes with few differences between
      HIC and LMIC countries. These differences likely reflect differences in health
      seeking behaviours and health services, but high heterogeneity between studies
      limits conclusions about the effect size.

PMID- 29197155
TI  - High-intensity interval training improves insulin sensitivity in older
      individuals.
AB  - AIM: Metabolic health may deteriorate with age as a result of altered body
      composition and decreased physical activity. Endurance exercise is known to
      counter these changes delaying or even preventing onset of metabolic diseases.
      High-intensity interval training (HIIT) is a time efficient alternative to
      regular endurance exercise, and the aim of this study was to investigate the
      metabolic benefit of HIIT in older subjects. METHODS: Twenty-two sedentary male
      (n = 11) and female (n = 11) subjects aged 63 +/- 1 years performed HIIT training
      three times/week for 6 weeks on a bicycle ergometer. Each HIIT session consisted
      of five 1-minute intervals interspersed with 11/2-minute rest. Prior to the first
      and after the last HIIT session whole-body insulin sensitivity, measured by a
      hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic
      parameters, body composition and maximal oxygen uptake were assessed. Muscle
      biopsies were obtained wherefrom content of glycogen and proteins involved in
      muscle glucose handling were determined. RESULTS: Insulin sensitivity (P = .011)
      and maximal oxygen uptake increased (P < .05) in both genders, while plasma
      cholesterol (P < .05), low-density lipoprotein (P < .05), visceral fat mass (P <
      .05) and per cent body fat (P < .05) decreased after 6 weeks of HIIT. HbA1c
      decreased only in males (P = .001). Muscle glycogen content increased in both
      genders (P = .001) and in line GLUT4 (P < .05), glycogen synthase (P = .001) and
      hexokinase II (P < .05) content all increased. CONCLUSION: Six weeks of HIIT
      significantly improves metabolic health in older males and females by reducing
      age-related risk factors for cardiometabolic disease.

PMID- 29197156
TI  - Identification of aggregates in therapeutic formulations of recombinant full
      length factor VIII products by sedimentation velocity analytical
      ultracentrifugation.
AB  - : Essentials Factor VIII inhibitors are the most serious complication in patients
      with hemophilia A. Aggregates in biopharmaceutical products are an immunogenic
      risk factor. Aggregates were identified in recombinant full-length factor VIII
      products. Aggregates in recombinant factor VIII products are identified by
      analytical ultracentrifugation. SUMMARY: Background The development of inhibitory
      anti-factor VIII antibodies is the most serious complication in the management of
      patients with hemophilia A. Studies have suggested that recombinant full-length
      FVIII is more immunogenic than plasma-derived FVIII, and that, among recombinant
      FVIII products, Kogenate is more immunogenic than Advate. Aggregates in
      biopharmaceutical products are considered a risk factor for the development of
      anti-drug antibodies. Objective To evaluate recombinant full-length FVIII
      products for the presence of aggregates. Methods Advate, Helixate and Kogenate
      were reconstituted to their therapeutic formulations, and subjected to
      sedimentation velocity (SV) analytical ultracentrifugation (AUC). Additionally,
      Advate and Kogenate were concentrated and subjected to buffer exchange by
      ultrafiltration to remove viscous cosolvents for the purpose of measuring s20,w
      values and molecular weights. Results The major component of all three products
      was a population of ~7.5 S heterodimers with a weight-average molecular weight of
      ~230 kDa. Helixate and Kogenate contained aggregates ranging from 12 S to at
      least 100 S, representing ~ 20% of the protein mass. Aggregates greater than 12 S
      represented < 3% of the protein mass in Advate. An approximately 10.5 S
      aggregate, possibly representing a dimer of heterodimers, was identified in
      buffer-exchanged Advate and Kogenate. SV AUC analysis of a plasma-derived FVIII
      product was confounded by the presence of von Willebrand factor in molar excess
      over FVIII. Conclusions Aggregate formation has been identified in recombinant
      full-length FVIII products, and is more extensive in Helixate and Kogenate than
      in Advate. SV AUC is an important method for characterizing FVIII products.

PMID- 29197157
TI  - Application of the ISNT rules on retinal nerve fibre layer thickness and
      neuroretinal rim area in healthy myopic eyes.
AB  - PURPOSE: We determined the applicability of inferior > superior > nasal >
      temporal (ISNT) rules on retinal nerve fibre layer (RNFL) thickness and rim area
      and evaluated the impact of various ocular factors on the performance of the ISNT
      rules in healthy myopic eyes. METHODS: A total of 138 eyes from 138 healthy
      myopic subjects were included in this cross-sectional observational study. The
      peripapillary RNFL and optic disc in each eye were imaged with Cirrus HD optical
      coherence tomography (OCT) and Heidelberg Retina Tomograph II (HRT2),
      respectively. The performance of the inferior > superior (IS), inferior >
      superior > nasal > temporal (IST) and ISNT rules on RNFL thickness and rim area
      was determined and compared between low-to-moderate myopia and high myopia. The
      effects of ocular factors [including axial length, disc area, disc tilt, disc
      torsion, disc-fovea angle (DFA) and retina artery angle] on the performance of
      ISNT rules were evaluated with logistic regression analysis. RESULTS: The mean
      axial length and refractive error were 25.57 +/- 1.09 mm (range, 22.52-28.77 mm)
      and -5.12 +/- 2.30 D [range, -9.63 to -0.50 dioptres (D)], respectively. Sixty
      three per cent of the healthy eyes were compliant with the ISNT rule on rim area,
      while ISNT rule on RNFL thickness was followed in only 11.6% of the included
      eyes. For rim area, smaller disc area was significantly associated with increased
      compliance of the IS rule (odds ratio: 0.46, p = 0.039), IST rule (odds ratio:
      0.46, p = 0.037) and ISNT rule (odds ratio: 0.44, p = 0.030). For RNFL thickness,
      greater DFA was significantly associated with increased compliance of the IS and
      IST rules (odds ratio: 1.30, p < 0.001; odds ratio: 1.19, p = 0.006,
      respectively). CONCLUSION: In healthy myopic subjects, 88.4% and 37% of eyes did
      not comply with the ISNT rule on RNFL thickness and rim area, respectively. Due
      to significant low compliance in healthy eyes, the ISNT rule and its variants
      have limited potential utility in diagnosing glaucoma in myopic subjects.

PMID- 29197158
TI  - Design, synthesis, and molecular docking studies of N-(9,10-anthraquinone-2
      carbonyl)amino acid derivatives as xanthine oxidase inhibitors.
AB  - A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a-j) was
      designed and synthesized as novel xanthine oxidase inhibitors. Among them, the
      L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e
      and 1j) were effective with micromolar level potency. In particular, the L
      phenylalanine derivative 1d (IC50  = 3.0 MUm) and the D-phenylalanine derivative
      1i (IC50  = 2.9 MUm) presented the highest potency and were both more potent than
      the positive control allopurinol (IC50  = 8.1 MUm). Preliminary SAR analysis
      pointed that an aromatic amino acid fragment, for example, phenylalanine or
      tryptophan, was essential for the inhibition; the D-amino acid derivative
      presented equal or greater potency compared to its L-enantiomer; and the 9,10
      anthraquinone moiety was welcome for the inhibition. Molecular simulations
      provided rational binding models for compounds 1d and 1i in the xanthine oxidase
      active pocket. As a result, compounds 1d and 1i could be promising lead compounds
      for further investigation.

PMID- 29197159
TI  - Intra-ocular diathermy forceps.
AB  - PURPOSE: The purpose of this study was to develop intra-ocular diathermy forceps
      and test them on perfused porcine cadaver eyes. METHODS: We designed two types of
      23-gauge intra-ocular bipolar diathermy forceps by modifying commercially
      available membrane peeling forceps. In the first type, the emitting electrode is
      connected to one-half of the core and the return electrode to the other half,
      with one jaw of the forceps attached to each half. In the second type, the
      emitting electrode is attached to the core and both jaws of the forceps, and the
      return electrode to the surrounding tube. We compared the new diathermy forceps
      to conventional intra-ocular diathermy, on perfused porcine cadaver eyes. First
      order retinal artery and vein closure was confirmed both by a perfusion study and
      by histology of the treated vessels. RESULTS: Type 1 diathermy forceps closed
      retinal arteries and veins more successfully (five of five and five of five
      successful treatments, respectively) than Type 2 diathermy forceps (five of five
      and four of five, respectively) and conventional diathermy (three of five and
      four of five, respectively). Less energy was used with Type 1 compared to Type 2
      and conventional for artery closure (1.5 +/- 0.0 versus 4.6 +/- 3.3 versus 2.1 +/
      0.8 joules, respectively) and vein closure (1.5 +/- 0.0 versus 5.4 +/- 4.6
      versus 2.4 +/- 0.8 joules, respectively). Histology of the treated vessels
      confirmed the perfusion study results. CONCLUSION: We designed two types of a new
      multifunctional intra-ocular instrument with the ability to peel membranes and to
      grasp, compress and coagulate retinal blood vessels. Both types pose operational
      advantages compared to current conventional intra-ocular diathermy.

PMID- 29197161
TI  - Influenza-associated mortality in South Africa, 2009-2013: The importance of
      choices related to influenza infection proxies.
AB  - BACKGROUND: Regression modeling methods are commonly used to estimate influenza
      associated mortality using covariates such as laboratory-confirmed influenza
      activity in the population as a proxy of influenza incidence. OBJECTIVE: We
      examined the choices of influenza proxies that can be used from influenza
      laboratory surveillance data and their impact on influenza-associated mortality
      estimates. METHOD: Semiparametric generalized additive models with a smoothing
      spline were applied on national mortality data from South Africa and influenza
      surveillance data as covariates to obtain influenza-associated mortality
      estimates from respiratory causes from 2009 to 2013. Proxies examined included
      alternative ways of expressing influenza laboratory surveillance data such as
      weekly or yearly proportion or rate of positive samples, using influenza
      subtypes, or total influenza data and expressing the data as influenza season
      specific or across all seasons. RESULT: Based on model fit, weekly proportion and
      influenza subtype-specific proxy formulation provided the best fit. The choice of
      proxies used gave large differences to mortality estimates, but the 95%
      confidence interval of these estimates overlaps. CONCLUSION: Regardless of proxy
      chosen, mortality estimates produced may be broadly consistent and not
      statistically significant for public health practice.

PMID- 29197160
TI  - Compartment-specific dynamics and functions of autophagy in neurons.
AB  - Autophagy is a lysosomal degradation pathway that is critical to maintaining
      neuronal homeostasis and viability. Autophagy sequesters damaged and aged
      cellular components from the intracellular environment, and shuttles these
      diverse macromolecules to lysosomes for destruction. This active surveillance of
      the quality of the cytoplasm and organelles is essential in neurons to sustain
      their long-term functionality and viability. Indeed, defective autophagy is
      linked to neurodevelopmental abnormalities and neurodegeneration in mammals.
      Here, we review the mechanisms of autophagy in neurons and functional roles for
      autophagy in neuronal homeostasis. We focus on the compartment-specific dynamics
      of autophagy in neurons, and how autophagy might perform non-canonical functions
      critical for neurons. We suggest the existence of multiple populations of
      autophagosomes with compartment-specific functions important for neural activity
      and function. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 298-310,
      2018.

PMID- 29197162
TI  - Design, synthesis, and cytotoxic evaluation of novel furo[2,3-b]quinoline
      derivatives.
AB  - A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized
      by introducing benzyl ether, benzoate, and benzenesulfonate to 6-position of
      furo[2,3-b]quinoline and their chemical structures were confirmed by ESI-MS, 1 H
      NMR, and 13 C NMR spectra. All target compounds were evaluated in vitro against
      four human cancer cell lines (HCT-116, MCF-7, U2OS, and A549) by MTT method.
      Cytotoxic assay showed that compounds 8a, 8e, 10a, 10b, and 10c exhibited more
      potent cytotoxicities compared to 2-bromine-6-hydroxy-furo-[2,3-b]quinoline (7).
      Compound 10c exhibited higher antiproliferative activity (IC50 values ranging
      from 4.32 to 24.96 MUm) against four human cancer cell lines (HCT-116, MCF-7,
      U2OS, and A549) and weak cytotoxicity on normal cell HL-7702, which suggested
      that 10c might be an ideal anticancer candidate. Compounds 8a, 10a, 10b showed
      good selectivities to MCF-7 and HCT-116, which could be considered as ideal
      selective candidates for further study. The SARs showed that the introduction of
      the benzyl ether and benzenesulfonate could significantly improve cytotoxicities,
      while the benzoate failed to enhance potency obviously.

PMID- 29197163
TI  - Model for pressure drop and flow deflection in the numerical simulation of stents
      in aneurysms.
AB  - The numerical simulation of flow diverters like stents contributes to the
      development and improvement of endovascular stenting procedures, leading
      ultimately to an improved treatment of intracranial aneurysms. Due to the scale
      difference between the struts of flow diverters and the full artery, it is common
      to avoid fully resolved simulations at the level of the stent porosity. Instead,
      the effect of stents on the flow is represented by a heuristic continuum model.
      However, the commonly used porous media models describe the properties of flow
      diverters only partially, because they do not explicitly account for the
      deflection of the flow direction by the stent. We show that this deficiency can
      be circumvented by adopting the theoretical framework of screen models. The
      article first reviews existing screen models. It then proposes an explicit
      formula for the drag and the deflection coefficient, as predicted by each model,
      for both perpendicular and inclined angles. The results of 2D numerical
      simulations are used to formulate a generalization of these formulas, to achieve
      best results in the case of stent modeling. The obtained model is then validated,
      again through 2D numerical simulation.

PMID- 29197164
TI  - Epidemiology and morphology of full-thickness macular holes.
AB  - PURPOSE: To investigate the incidence of full-thickness macular holes (FTMHs) and
      their morphological features according to the International Vitreomacular
      Traction Study (IVTS) classification. METHODS: The clinical records of all new
      patients with FTMH, referred between 2008 and 2014, were reviewed for
      demographics, cause of the FTMH, age at diagnosis, symptom duration, laterality,
      visual acuity (VA), axial length and lens status. A detailed analysis of the
      patients' spectral domain optical coherence tomography (SD-OCT) images was
      performed, and the primary FTMHs were classified in clinical stages according to
      the IVTS classification. From the SD-OCT, accurate macula drawings were made by
      means of a computer-drawing software. By merging these drawings and displaying
      them as colour-coded maps, the morphology and shape of the FTMH were visualized.
      RESULTS: The study included 177 eyes (152 primary and 25 secondary FTMH) in 166
      patients. In primary FTMH, the male-to-female ratio was 1:2.2. The age- and
      gender-adjusted annual incidences of primary FTMH were 7.9 eyes and 7.4
      individuals per 100 000 inhabitants. Mean primary FTMH minimum linear diameter
      (MLD) and basal diameter (BD) were 435 MUm and 872 MUm, respectively, and 13%
      were classified as small, 31% as medium and 55% as large. Vitreomacular traction
      (VMT) and epiretinal membrane (ERM) were present in 34% and 36% of the eyes,
      respectively. CONCLUSION: This study provides data on the incidence rates of FTMH
      adjusted to different standard populations. The morphological analysis and novel
      computational visualization technique offer new insight into the structural
      complexity of FTMH and how VMT and ERM significantly influence FTMH
      configuration.

PMID- 29197165
TI  - The treatment of postoperative endophthalmitis: should we still follow the
      endophthalmitis vitrectomy study more than two decades after its publication?
AB  - Conducted in the early 1990s Endophthalmitis Vitrectomy Study (EVS) have helped
      in establishing reasonable guidelines for the management of infectious
      postoperative endophthalmitis. However at present, more than 20 years after its
      publication, tremendous progress has been introduced in vitrectomy technology,
      which now permits the vitreoretinal surgeon to perform surgery more safely, and
      with better outcomes. Moerover, performing a complete vitreous removal, along
      with the moving up of the surgical intervention to as early as possible allows
      the prevention of complications that would limit the functional improvement
      postoperatively. Thus, it is now highly needed to re-evaluate the conclusions of
      the EVS study.

PMID- 29197166
TI  - Early postnatal development of electrophysiological and histological properties
      of sensory sural nerves in male rats that were maternally deprived and
      artificially reared: Role of tactile stimulation.
AB  - Early adverse experiences disrupt brain development and behavior, but little is
      known about how such experiences impact on the development of the peripheral
      nervous system. Recently, we found alterations in the electrophysiological and
      histological characteristics of the sensory sural (SU) nerve in maternally
      deprived, artificially reared (AR) adult male rats, as compared with maternally
      reared (MR) control rats. In the present study, our aim was to characterize the
      ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were
      (1) AR group, (2) AR and received daily tactile stimulation to the body and
      anogenital region (AR-Tactile group); or (3) reared by their mother (MR group).
      At PND 7, 14, or 21, electrophysiological properties and histological
      characteristics of the SU nerves were assessed. At PND 7, the
      electrophysiological properties and most histological parameters of the SU nerve
      did not differ among MR, AR, and AR-Tactile groups. By contrast, at PND 14 and/or
      21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a
      significant reduction in myelin area and myelin thickness, which were accompanied
      by a reduction in axon area (day 21 only) compared to the nerves of MR rats.
      Tactile stimulation (AR-Tactile group) partially prevented most of these
      alterations. These results suggest that sensory cues from the mother and/or
      littermates during the first 7-14 PND are relevant for the proper development and
      function of the adult SU nerve. (c) 2017 Wiley Periodicals, Inc. Develop
      Neurobiol 78: 351-362, 2018.

PMID- 29197167
TI  - To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects
      Labeling for Oral Antineoplastic Drugs.
AB  - There has been controversy regarding whether bioavailability of certain oral
      oncology drugs should be maximized by taking these medications with food,
      irrespective of label instructions in the dosing and administration section. To
      provide insight into this controversy, we conducted an in-depth analysis for oral
      antineoplastic drugs approved by the Food and Drug Administration in 2000-2016
      and identified important issues influencing food labeling decisions. Furthermore,
      a case study involving sonidegib, a drug approved for locally advanced basal cell
      carcinoma with a significant food effect on exposure, was used to demonstrate the
      consequences of failure to adhere to food label recommendations using drug
      specific population pharmacokinetic and exposure-toxicity models. In 2000-2009,
      80% (4 out of 5) of all approved oral antineoplastics with increased
      bioavailability in the fed state were labeled as "take on empty stomach." In
      contrast, we found that in 2010-2016 there is a greater diversity in food
      recommendations for drugs with increased bioavailability in the fed state.
      Currently, many oral oncology drugs are given with food to maximize their
      bioavailability; however, as seen from our case study of sonidegib, failure to
      fully adhere to label recommendations to either take with food or not could lead
      to adverse consequences in terms of safety and efficacy.

PMID- 29197168
TI  - Dissociation between executed and imagined bimanual movements in autism spectrum
      conditions.
AB  - : Autism spectrum conditions (ASC) are characterized by social-communicative
      deficits and repetitive stereotyped behaviors. Altered motor coordination is also
      observed and a dysfunction of motor imagery has been recently reported on
      implicit tasks. However, no information on explicit motor imagery abilities is
      available in ASC. Here, we employed a spatial bimanual task to concurrently
      assess motor coordination and explicit motor imagery in autism. A secondary
      objective of the study was to evaluate these abilities across two populations of
      ASC, namely adolescents and adults with ASC. To this aim, we took advantage of
      the circles-lines task in which where participants were asked to continuously
      draw: right hand lines (unimanual condition); right hand lines and left hand
      circles (bimanual condition); right hand lines while imagining to draw left hand
      circles (imagery condition). For each participant, an Ovalization Index (OI) was
      calculated as a deviation of the right hand drawing trajectory from an absolute
      vertical axis. Results showed a significant and similar coupling effect in the
      bimanual condition (i.e., a significant increase of the OI values with respect to
      the unimanual condition) in both controls and ASC participants. On the contrary,
      in the imagery condition, a significant coupling effect was found only in
      controls. Furthermore, adult controls showed a significantly higher imagery
      coupling effect in comparison to all the other groups. These results demonstrate
      that atypical motor imagery processes in ASC are not limited to implicit tasks
      and suggest that development of neural structures involved in motor imagery are
      immature in ASC. Autism Res 2018, 11: 376-384. (c) 2017 International Society for
      Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism spectrum conditions
      (ASC) are characterized by social-communicative and motor coordination
      difficulties but in many cases also by an impaired capability to imagine
      movements. In this study we found that while two handed coordination in ASC can
      be developed as well as in typically developed persons, the development of motor
      imagery could still be immature in ASC, leading to difficulties in imagining,
      understanding as well as programming and coordinating complex movements.

PMID- 29197169
TI  - Human like me: Evidence that I-sharing humanizes the otherwise dehumanized.
AB  - People persistently undermine the humanness of outgroup members, leaving
      researchers perplexed as to how to address this problem of 'dehumanization'
      (Haslam & Loughnan, , Ann Rev of Psychol, 65, 399; Leyens, , Group Process
      Intergroup Relat, 12, 807). Here, we test whether I-sharing (i.e., sharing a
      subjective experience) counters this tendency by promoting the humanization of
      outgroup members. In Study 1, White participants had a face-to-face meeting with
      a White or Black confederate and either did or did not I-share with this
      confederate. The extent to which participants humanized the outgroup member
      depended on whether or not they I-shared with her. Study 2 tested the effect of I
      sharing on the two distinct dimensions of dehumanization (Haslam, , Pers Soc
      Psychol Rev, 10, 252). Conceptually replicating the results of Study 1,
      participants who I-shared with a social class ingroup or outgroup member rated
      their partner as higher in human nature than those who did not I-share with their
      partner. These results add to the growing literature on I-sharing's implications
      for intergroup processes and suggest effective ways of tackling a persistent
      problem.

PMID- 29197170
TI  - December 2017 Issue of JCD.

PMID- 29197171
TI  - Evaluation of the effects of acne vulgaris on quality of life in Turkey by using
      TAQLI.
AB  - BACKGROUND: Acne vulgaris (AV) is a chronic, inflammatory skin disease that may
      cause various psychiatric and/or psychological problems. OBJECTIVE: In this
      study, we aimed to determine the effect of AV on the quality of life in the
      Turkish population using the Turkish Acne Quality of Life Index (TAQLI). METHODS:
      A total of 960 patients with AV who attended the dermatology department were
      included in the study. Acne severity was determined using the global acne
      classification system. TAQLI was used to evaluate the effect of acne on quality
      of life. RESULTS: The 960 patients consisted of 673 (70.1%) females and 287
      (29.9%) males. There were 536 (55.8%) patients under the age of 20, 386 (40.2%)
      aged 20-30, and 38 (4.0%) over 30. Acne duration varied between 1 and 20 years,
      and the mean duration was 2.95 +/- 2.53 years. The mean TAQLI value of all
      patients was 20.8 +/- 9.5. The mean TAQLI value was statistically significantly
      higher in female patients, in patients with an acne duration of more than 2
      years, and in those with very severe acne. However, no statistically significant
      difference was found between the age groups. CONCLUSION: We observed that the
      quality of life in patients with AV was affected, and this effect was more
      significant in female patients, patients with severe acne and longer acne
      duration. We believe that the psychiatric/psychological effects should be
      followed up closely in this group of patients.

PMID- 29197172
TI  - Sleep patterns predictive of daytime challenging behavior in individuals with low
      functioning autism.
AB  - : Increased severity of problematic daytime behavior has been associated with
      poorer sleep quality in individuals with autism spectrum disorder. In this work,
      we investigate whether this relationship holds in a real-time setting, such that
      an individual's prior sleep can be used to predict their subsequent daytime
      behavior. We analyzed an extensive real-world dataset containing over 20,000
      nightly sleep observations matched to subsequent challenging daytime behaviors
      (aggression, self-injury, tantrums, property destruction and a challenging
      behavior index) across 67 individuals with low-functioning autism living in two
      U.S. residential facilities. Using support vector machine classifiers, a
      statistically significant predictive relationship was found in 81% of individuals
      studied (P < 0.05). For all five behaviors examined, prediction accuracy
      increased up to approximately eight nights of prior sleep used to make the
      prediction, indicating that the behavioral effects of sleep may manifest on
      extended timescales. Accurate prediction was most strongly driven by sleep
      variability measures, highlighting the importance of regular sleep patterns. Our
      findings constitute an initial step towards the development of a real-time
      monitoring tool to pre-empt behavioral episodes and guide prophylactic treatment
      for individuals with autism. Autism Res 2018, 11: 391-403. (c) 2017 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We analyzed
      over 20,000 nights of sleep from 67 individuals with autism to investigate
      whether daytime behaviors can be predicted from prior sleep patterns. Better-than
      chance accuracy was obtained for 81% of individuals, with measures of night-to
      night variation in sleep timing and duration most relevant for accurate
      prediction. Our results highlight the importance of regular sleep patterns for
      better daytime functioning and represent a step toward the development of 'smart
      sleep technologies' to pre-empt behavior in individuals with autism.

PMID- 29197173
TI  - Evaluation of data sources and approaches for estimation of influenza-associated
      mortality in India.
AB  - BACKGROUND: No estimates of influenza-associated mortality exist for India.
      OBJECTIVE: To evaluate national mortality and viral surveillance data from India
      for assessing their appropriateness in estimating influenza-associated mortality
      using varied analytic approaches. METHODS: We reviewed influenza virus
      surveillance data from a national influenza surveillance network. We also
      reviewed national mortality data from Civil Registration System (CRS), Medical
      Certification of Cause of Death (MCCD) and the Sample Registration System (SRS).
      We compared and scored the different sources of mortality data using specific
      criteria, including the process of cause of death assignment, sample size,
      proportion of ill-defined deaths, representativeness and availability of time
      series data. Each of these 5 parameters was scored on a scale from 1 to 5. To
      evaluate how to generate an influenza-associated mortality estimate for India, we
      also reviewed 4 methodologic approaches to assess the appropriateness of their
      assumptions and requirements for these data sets. RESULTS: The influenza virus
      surveillance data included year-round sample testing for influenza virus and was
      found to be suitable for influenza mortality estimation modelling. Based on
      scoring for the 5 mortality data criteria, the SRS data had the highest score
      with 20 of 25 possible score, whereas MCCD and CRS scored 16 and 12,
      respectively. The SRS which used verbal autopsy survey methods was determined to
      be nationally representative and thus adequate for estimating influenza
      associated mortality. Evaluation of the modelling methods demonstrated that
      Poisson regression, risk difference and mortality multiplier methods could be
      applied to the Indian setting. CONCLUSION: Despite significant challenges, it is
      possible to estimate influenza-associated mortality in India.

PMID- 29197174
TI  - Estimates of seasonal influenza-associated mortality in Bangladesh, 2010-2012.
AB  - BACKGROUND: Seasonal influenza-associated mortality estimates help identify the
      burden of disease and assess the value of public health interventions such as
      annual influenza immunization. Vital registration is limited in Bangladesh making
      it difficult to estimate seasonal influenza mortality. OBJECTIVES: Our study
      aimed to estimate seasonal influenza-associated mortality rates for 2010-2012 in
      Bangladesh. METHODS: We conducted surveillance among hospitalized patients with
      severe acute respiratory illness (SARI) for persons aged >=5 years and severe
      pneumonia for children <5 years in 11 sites across Bangladesh. We defined the
      catchment areas of these sites and conducted a community survey in 22 randomly
      selected unions (administrative units) within the catchment areas to identify
      respiratory deaths. We multiplied the proportion of influenza-positive patients
      at our surveillance sites by the age-specific number of respiratory deaths
      identified to estimate seasonal influenza-associated mortality. RESULTS: Among
      4221 surveillance case-patients, 553 (13%) were positive for influenza viruses.
      Concurrently, we identified 1191 persons who died within 2 weeks of developing an
      acute respiratory illness within the catchment areas of the surveillance
      hospitals. In 2010-2011, the estimated influenza-associated mortality rate was 6
      (95% CI 4-9) per 100 000 for children <5 years and 41 (95% CI 35-47) per 100 000
      for persons >60 years. During 2011-2012, the estimated influenza-associated
      mortality rate was 13 (95% CI 10-16) per 100 000 among children <5 years and 88
      (95% CI 79-98) per 100 000 among persons aged >60 years. CONCLUSIONS: We
      identified a substantial burden of influenza-associated deaths in Bangladesh
      suggesting that the introduction of prevention and control measures including
      seasonal vaccination should be considered by local public health decision-makers.

PMID- 29197175
TI  - Pharmacokinetics of Diclofenac and Hydroxypropyl-beta-Cyclodextrin (HPbetaCD)
      Following Administration of Injectable HPbetaCD-Diclofenac in Subjects With Mild
      to Moderate Renal Insufficiency or Mild Hepatic Impairment.
AB  - Given their established analgesic properties, nonsteroidal anti-inflammatory
      drugs (NSAIDs) represent an important postoperative pain management option. This
      study investigated: (1) the effects of mild or moderate renal insufficiency and
      mild hepatic impairment on the pharmacokinetics (PK) of diclofenac and
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) following administration of the
      injectable NSAID HPbetaCD-diclofenac; and (2) the PK of HPbetaCD following
      administration of HPbetaCD-diclofenac and intravenous itraconazole formulated
      with HPbetaCD in healthy adults. Diclofenac clearance (CL) and volume of
      distribution (Vz ) tended to increase with decreasing renal function (moderate
      insufficiency versus mild insufficiency or healthy controls). Regression analysis
      demonstrated a significant relationship between Vz (but not CL or elimination
      half-life, t1/2 ) and renal function. HPbetaCD CL was significantly decreased in
      subjects with renal insufficiency, with a corresponding increase in t1/2 . There
      were no significant differences in diclofenac or HPbetaCD PK in subjects with
      mild hepatic impairment versus healthy subjects. Exposure to HPbetaCD in healthy
      subjects following HPbetaCD-diclofenac administration was ~12% of that with
      intravenous itraconazole, after adjusting for dosing schedule and predicted
      accumulation (<5% without adjustment). With respect to PK properties, these
      results suggest that HPbetaCD-diclofenac might be administered to patients with
      mild or moderate renal insufficiency or mild hepatic impairment without dose
      adjustment (NCT00805090).

PMID- 29197176
TI  - Toward real-time diffuse optical tomography: accelerating light propagation
      modeling employing parallel computing on GPU and CPU.
AB  - Parameter recovery in diffuse optical tomography is a computationally expensive
      algorithm, especially when used for large and complex volumes, as in the case of
      human brain functional imaging. The modeling of light propagation, also known as
      the forward problem, is the computational bottleneck of the recovery algorithm,
      whereby the lack of a real-time solution is impeding practical and clinical
      applications. The objective of this work is the acceleration of the forward
      model, within a diffusion approximation-based finite-element modeling framework,
      employing parallelization to expedite the calculation of light propagation in
      realistic adult head models. The proposed methodology is applicable for modeling
      both continuous wave and frequency-domain systems with the results demonstrating
      a 10-fold speed increase when GPU architectures are available, while maintaining
      high accuracy. It is shown that, for a very high-resolution finite-element model
      of the adult human head with ~600,000 nodes, consisting of heterogeneous layers,
      light propagation can be calculated at ~0.25  s/excitation source.

PMID- 29197177
TI  - Parametric imaging of collagen structural changes in human osteoarthritic
      cartilage using optical polarization tractography.
AB  - Collagen degeneration is an important pathological feature of osteoarthritis. The
      purpose of this study is to investigate whether the polarization-sensitive
      optical coherence tomography (PSOCT)-based optical polarization tractography
      (OPT) can be useful in imaging collagen structural changes in human
      osteoarthritic cartilage samples. OPT eliminated the banding artifacts in
      conventional PSOCT by calculating the depth-resolved local birefringence and
      fiber orientation. A close comparison between OPT and PSOCT showed that OPT
      provided improved visualization and characterization of the zonal structure in
      human cartilage. Experimental results obtained in this study also underlined the
      importance of knowing the collagen fiber orientation in conventional polarized
      light microscopy assessment. In addition, parametric OPT imaging was achieved by
      quantifying the surface roughness, birefringence, and fiber dispersion in the
      superficial zone of the cartilage. These quantitative parametric images provided
      complementary information on the structural changes in cartilage, which can be
      useful for a comprehensive evaluation of collagen damage in osteoarthritic
      cartilage.

PMID- 29197178
TI  - Optical coherence tomography and computer-aided diagnosis of a murine model of
      chronic kidney disease.
AB  - Chronic kidney disease (CKD) is characterized by a progressive loss of renal
      function over time. Histopathological analysis of the condition of glomeruli and
      the proximal convolutional tubules over time can provide valuable insights into
      the progression of CKD. Optical coherence tomography (OCT) is a technology that
      can analyze the microscopic structures of a kidney in a nondestructive manner.
      Recently, we have shown that OCT can provide real-time imaging of kidney
      microstructures in vivo without administering exogenous contrast agents. A murine
      model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by
      OCT. OCT images of the rat kidneys have been captured every week up to eight
      weeks. Tubular diameter and hypertrophic tubule population of the kidneys at
      multiple time points after ADR injection have been evaluated through a fully
      automated computer-vision system. Results revealed that mean tubular diameter and
      hypertrophic tubule population increase with time in post-ADR injection period.
      The results suggest that OCT images of the kidney contain abundant information
      about kidney histopathology. Fully automated computer-aided diagnosis based on
      OCT has the potential for clinical evaluation of CKD conditions.

PMID- 29197179
TI  - Metagenomic Investigation of Idiopathic Meningoencephalomyelitis in Dogs.
AB  - BACKGROUND: Meningoencephalomyelitis of unknown origin (MUO) is a common and life
      threatening neuroinflammatory disease in dogs. Features of the disease are
      suggestive of an underlying immune-mediated process, but the association of this
      disease with a pathogen is still unknown. HYPOTHESIS/OBJECTIVES: To search for
      candidate etiologic agent associated with cases if MUO using next generation
      metagenomic sequencing. ANIMALS: Twenty-two dogs diagnosed with either MUO
      (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with
      MUO (11/22; 11 CSF and 2 brain) that served as negative controls. METHODS: A case
      control study was performed by identifying MUO and non-MUO cases. Samples were
      blindly processed and then unblinded for comparative analyses. Inclusion criteria
      for MUO cases included consistent MRI lesions and inflammatory CSF with a
      negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with
      glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh
      frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA
      and DNA were extracted separately for shotgun metagenomic sequencing. Known
      positive samples were used as controls to validate our sequencing and analysis
      pipelines and to establish limits of detection. Sequencing results were analyzed
      at a nucleotide and protein level for broad comparison to known infectious
      organisms. RESULTS: No candidate etiologic agents were identified in dogs with
      MUO. CONCLUSIONS AND CLINICAL IMPORTANCE: These results support but do not prove
      the hypothesis that MUO is not associated with infectious agents and might be an
      autoimmune disease.

PMID- 29197180
TI  - Acupuncture for neuropathic pain in adults.
AB  - BACKGROUND: Neuropathic pain may be caused by nerve damage, and is often followed
      by changes to the central nervous system. Uncertainty remains regarding the
      effectiveness and safety of acupuncture treatments for neuropathic pain, despite
      a number of clinical trials being undertaken. OBJECTIVES: To assess the analgesic
      efficacy and adverse events of acupuncture treatments for chronic neuropathic
      pain in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four
      Chinese databases, ClinicalTrials.gov and World Health Organization (WHO)
      International Clinical Trials Registry Platform (ICTRP) on 14 February 2017. We
      also cross checked the reference lists of included studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) with treatment duration of eight weeks or
      longer comparing acupuncture (either given alone or in combination with other
      therapies) with sham acupuncture, other active therapies, or treatment as usual,
      for neuropathic pain in adults. We searched for studies of acupuncture based on
      needle insertion and stimulation of somatic tissues for therapeutic purposes, and
      we excluded other methods of stimulating acupuncture points without needle
      insertion. We searched for studies of manual acupuncture, electroacupuncture or
      other acupuncture techniques used in clinical practice (such as warm needling,
      fire needling, etc). DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedures expected by Cochrane. The primary outcomes were pain
      intensity and pain relief. The secondary outcomes were any pain-related outcome
      indicating some improvement, withdrawals, participants experiencing any adverse
      event, serious adverse events and quality of life. For dichotomous outcomes, we
      calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous
      outcomes we calculated the mean difference (MD) with 95% CI. We also calculated
      number needed to treat for an additional beneficial outcome (NNTB) where
      possible. We combined all data using a random-effects model and assessed the
      quality of evidence using GRADE to generate 'Summary of findings' tables. MAIN
      RESULTS: We included six studies involving 462 participants with chronic
      peripheral neuropathic pain (442 completers (251 male), mean ages 52 to 63
      years). The included studies recruited 403 participants from China and 59 from
      the UK. Most studies included a small sample size (fewer than 50 participants per
      treatment arm) and all studies were at high risk of bias for blinding of
      participants and personnel. Most studies had unclear risk of bias for sequence
      generation (four out of six studies), allocation concealment (five out of six)
      and selective reporting (all included studies). All studies investigated manual
      acupuncture, and we did not identify any study comparing acupuncture with
      treatment as usual, nor any study investigating other acupuncture techniques
      (such as electroacupuncture, warm needling, fire needling).One study compared
      acupuncture with sham acupuncture. We are uncertain if there is any difference
      between the two interventions on reducing pain intensity (n = 45; MD -0.4, 95% CI
      -1.83 to 1.03, very low-quality evidence), and neither group achieved 'no worse
      than mild pain' (visual analogue scale (VAS, 0-10) average score was 5.8 and 6.2
      respectively in the acupuncture and sham acupuncture groups, where 0 = no pain).
      There was limited data on quality of life, which showed no clear difference
      between groups. Evidence was not available on pain relief, adverse events or
      other pre-defined secondary outcomes for this comparison.Three studies compared
      acupuncture alone versus other therapies (mecobalamin combined with nimodipine,
      and inositol). Acupuncture may reduce the risk of 'no clinical response' to pain
      than other therapies (n = 209; RR 0.25, 95% CI 0.12 to 0.51), however, evidence
      was not available for pain intensity, pain relief, adverse events or any of the
      other secondary outcomes.Two studies compared acupuncture combined with other
      active therapies (mecobalamin, and Xiaoke bitong capsule) versus other active
      therapies used alone. We found that the acupuncture combination group had a lower
      VAS score for pain intensity (n = 104; MD -1.02, 95% CI -1.09 to -0.95) and
      improved quality of life (n = 104; MD -2.19, 95% CI -2.39 to -1.99), than those
      receiving other therapy alone. However, the average VAS score of the acupuncture
      and control groups was 3.23 and 4.25 respectively, indicating neither group
      achieved 'no worse than mild pain'. Furthermore, this evidence was from a single
      study with high risk of bias and a very small sample size. There was no evidence
      on pain relief and we identified no clear differences between groups on other
      parameters, including 'no clinical response' to pain and withdrawals. There was
      no evidence on adverse events.The overall quality of evidence is very low due to
      study limitations (high risk of performance, detection, and attrition bias, and
      high risk of bias confounded by small study size) or imprecision. We have limited
      confidence in the effect estimate and the true effect is likely to be
      substantially different from the estimated effect. AUTHORS' CONCLUSIONS: Due to
      the limited data available, there is insufficient evidence to support or refute
      the use of acupuncture for neuropathic pain in general, or for any specific
      neuropathic pain condition when compared with sham acupuncture or other active
      therapies. Five studies are still ongoing and seven studies are awaiting
      classification due to the unclear treatment duration, and the results of these
      studies may influence the current findings.

PMID- 29197181
TI  - Investigating the strategies for microbial production of trehalose from
      lignocellulosic sugars.
AB  - Trehalose, a multi-functional and value-added disaccharide, can be efficiently
      biosynthesized from glucose by using a synergetic carbon utilization mechanism
      (SynCar) which coupled phosphoenolpyruvate (PEP) generation from the second
      carbon source with PEP-dependent phosphotransferase system (PTS) to promote non
      catabolic use of glucose. Considering glucose and xylose present in large amounts
      in lignocellulosic sugars, we explored new strategies for conversion of both
      sugars into trehalose. Herein, we first attempted trehalose production from
      xylose directly, based on which, synergetic utilization of glucose, and xylose
      prompted by SynCar was implemented in engineered Escherichia coli. As the
      results, the final titer of trehalose reached 5.55 g/L in shake flask
      experiments. The conversion ratio or utilization efficiency of glucose or xylose
      to trehalose was around fourfold higher than that of the original strain (YW-3).
      This work not only demonstrated the possibility of directly converting xylose (C5
      sugar) into trehalose (C12 disaccharide), but also suggested a promising strategy
      for trehalose production from lignocellulosic sugars for the first time.

PMID- 29197183
TI  - Production of itaconic acid from acetate by engineering acid-tolerant Escherichia
      coli W.
AB  - Utilization of abundant and cheap carbon sources can effectively reduce the
      production cost and enhance the economic feasibility. Acetate is a promising
      carbon source to achieve cost-effective microbial processes. In this study, we
      engineered an Escherichia coli strain to produce itaconic acid from acetate. As
      acetate is known to inhibit cell growth, we initially screened for a strain with
      a high tolerance to 10 g/L of acetate in the medium, and the W strain was
      selected as the host. Subsequently, the WC strain was obtained by overexpression
      of cad (encoding cis-aconitate decarboxylase) using a synthetic promoter and 5'
      UTR. However, the WC strain produced only 0.13 g/L itaconic acid because of low
      acetate uptake. To improve the production, the acetate assimilating pathway and
      glyoxylate shunt pathway were amplified by overexpression of pathway genes as
      well as its deregulation. The resulting strain, WCIAG4 produced 3.57 g/L itaconic
      acid (16.1% of theoretical maximum yield) after 88 hr of fermentation with rapid
      acetate assimilation. These efforts support that acetate can be a potential
      feedstock for biochemical production with engineered E. coli.

PMID- 29197182
TI  - Protection of macrophages from intracellular pathogens by miR-182-5p mimic-a gene
      expression meta-analysis approach.
AB  - The goals of this study were to (a) define which host genes are of particular
      importance during the interactions between macrophages and intracellular
      pathogens, and (b) use this knowledge to gain fresh, experimental understanding
      of how macrophage activities may be manipulated during host defense. We designed
      an in silico method for meta-analysis of microarray gene expression data, and
      used this to combine data from 16 different studies of cells in the monocyte
      macrophage lineage infected with seven different pathogens. Three thousand four
      hundred ninety-eight genes were identified, which we call the macrophage
      intracellular pathogen response (macIPR) gene set. As expected, the macIPR gene
      set showed a strong bias toward genes previously associated with the immune
      response. Predicted target sites for miR-182-5p (miR-182) were strongly over
      represented among macIPR genes, indicating an unexpected role for miR-182
      regulatable genes during intracellular pathogenesis. We therefore transfected
      primary human alveolar macrophage-like monocyte-derived macrophages from multiple
      different donors with synthetic miR-182, and found that miR-182 overexpression
      (a) increases proinflammatory gene induction during infection with Francisella
      tularensis live vaccine strain (LVS), (b) primes macrophages for increased
      autophagy, and (c) enhances macrophage control of both gram negative F.
      tularensisLVS and gram positive Bacillus anthracisANR-1 spores. These data
      therefore suggest a new application for miR-182 in promoting resistance to
      intracellular pathogens.

PMID- 29197184
TI  - Constructing a cellulosic yeast host with an efficient cellulase cocktail.
AB  - Cellulose is a renewable feedstock for green industry. It is therefore important
      to develop a technique to construct a host with a high cellulolytic efficiency to
      digest cellulose. In this study, we developed a convenient host-engineering
      technique to adjust the expression levels of heterologous genes in the host by
      promoter rearrangement and gene copy number adjustment. Using genes from
      different glycoside hydrolase (GH) families including GH2, GH3, GH5, GH6, GH7,
      and GH12 from Aspergillus niger, Trichoderma reesei, and Neocallimastix
      patriciarum, we constructed a cellulolytic Kluyveromyces marxianus with eight
      cellulase gene-cassettes that produced a cellulase cocktail with a high
      cellulolytic efficiency, leading to a significant reduction in enzyme cost in a
      rice straw saccharification process. Our technique can be used to design a host
      that can efficiently convert biomass feedstock to biofuel.

PMID- 29197185
TI  - Structure and interaction of Corynebacterium pseudotuberculosis cold shock
      protein A with Y-box single-stranded DNA fragment.
AB  - : Cold shock proteins (Csps) function to preserve cell viability at low
      temperatures by binding to nucleic acids and consequently control gene
      expression. The mesophilic bacterium Corynebacterium pseudotuberculosis is the
      causative agent of caseous lymphadenitis in animals, and infection in livestock
      is a considerable economic burden worldwide. In this report, the structure of
      cold shock protein A from Cp (Cp-CspA) and biochemical analysis of its
      temperature-dependent interaction with a Y-box ssDNA motif is presented. The Cp
      CspA structure contains five beta-strands making up a beta-barrel fold with 11
      hydrophobic core residues and two salt bridges that confers it with a melting
      temperature of ~ 54  degrees C that is similar to mesophilic Bs-CspB. Chemical
      shift perturbations analysis revealed that residues in the nucleic acid-binding
      motifs (RNP 1 and 2) and loop 3 are involved in binding to the Y-box fragment
      either by direct interaction or by conformational rearrangements remote from the
      binding region. Fluorescence quenching experiments of Cp-CspA showed that the
      dissociation constants for Y-box ssDNA binding is nanomolar and the binding
      affinity decreased as the temperature increased, indicating that the interaction
      is enthalpically driven and the hydrogen bonds and van der Waals forces are
      important contributions for complex stabilization. The Y31 of Cp-CspA is a
      particular occurrence among Csps from mesophilic bacteria that provide a possible
      explanation for the higher binding affinity to ssDNA than that observed for Bs
      CspB. Anisotropy measurements indicated that the reduction in molecular mobility
      of Cp-CspA upon Y-box binding is characterized by a cooperative process.
      DATABASE: Resonance assignment and structural data are available in the
      Biological Magnetic Resonance Data Bank and Protein Data Bank under accession
      number 26802 and 5O6F, respectively.

PMID- 29197186
TI  - Bartonella Seroepidemiology in Dogs from North America, 2008-2014.
AB  - BACKGROUND: Improved understanding of Bartonella species seroepidemiology in dogs
      may aid clinical decision making and enhance current understanding of naturally
      occurring arthropod vector transmission of this pathogen. OBJECTIVES: To identify
      demographic groups in which Bartonella exposure may be more likely, describe
      spatiotemporal variations in Bartonella seroreactivity, and examine co-exposures
      to other canine vector-borne diseases (CVBD). ANIMALS: A total of 15,451 serology
      specimens from dogs in North America were submitted to the North Carolina State
      University, College of Veterinary Medicine Vector Borne Disease Diagnostic
      Laboratory between January 1, 2008, and December 31, 2014. METHODS: Bartonella
      henselae, Bartonella koehlerae, and Bartonella vinsonii subspecies berkhoffii
      indirect fluorescent antibody (IFA) serology results, as well as results from a
      commercial assay kit screening for Dirofilaria immitis antigen and Ehrlichia
      species, Anaplasma phagocytophilum, and Borrelia burgdorferi antibodies, and
      Ehrlichia canis, Babesia canis, Babesia gibsoni, and Rickettsia species IFA
      results were reviewed retrospectively. RESULTS: Overall, 3.26% of dogs were
      Bartonella spp. seroreactive; B. henselae (2.13%) and B. koehlerae (2.39%) were
      detected more frequently than B. vinsonii subsp. berkhoffii (1.42%, P < 0.0001).
      Intact males had higher seroreactivity (5.04%) than neutered males (2.87%, P <
      0.0001) or intact or spayed females (3.22%, P = 0.0003). Mixed breed dogs had
      higher seroreactivity (4.45%) than purebred dogs (3.02%, P = 0.0002). There was
      no trend in seasonal seroreactivity; geographic patterns supported broad
      distribution of exposure, and co-exposure with other CVBD was common. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Bartonella spp. exposure was documented throughout North
      America and at any time of year. Male intact dogs, mixed breed dogs, and dogs
      exposed to other CVBD have higher seroreactivity to multiple Bartonella species.

PMID- 29197187
TI  - Development of a microfluidic platform for high-throughput screening of non-viral
      gene delivery vectors.
AB  - The grail of gene delivery is the development of delivery vectors as effective
      and non-cytotoxic as possible. In this regard, there is an urgent need of new
      tools for the straightforward and quantitative assessment of transfection
      efficiency and cytotoxicity simultaneously. We herein reported the development
      and validation of an easy-to-use lab-on-chip platform to perform cell
      transfection assays for unbiased, high-throughput selection of more and more
      effective gene delivery vectors by using two commercially sourced lipids,
      Lipofectamine 2000(r) and FuGene(r) 6. A single PDMS-layer platform was endowed
      with: i) a chaotic serial dilution generator, designed for the automatic
      generation of a linear lipoplex dilution (from 100% to 0% with 25% steps)
      independently delivered to; and ii) the downstream culture and transfection
      module consisting in five units, each composed of 33 serially connected and
      fluidically connected culture chambers for trapping small populations of ~10
      cells/chamber. In the absence of any transfectant, cells spread and duplicated up
      to 2 days. Besides, cells were transfected with EGFP-encoding reporter gene. The
      very facile visual inspection of the microdevice by means of a microscope and a
      semi-automated analytical method allowed pinpointing the best transfection
      conditions in terms of efficiency, cytotoxicity, cell doubling rates, and
      morphological changes at once.

PMID- 29197188
TI  - Genipin alleviates high-fat diet-induced hyperlipidemia and hepatic lipid
      accumulation in mice via miR-142a-5p/SREBP-1c axis.
AB  - Hyperlipidemia is a chronic disorder which plays an important role in the
      development of cardiovascular diseases, type 2 diabetes, atherosclerosis,
      hypertension, and nonalcoholic fatty liver disease. Genipin (GNP) is a metabolite
      from genipioside, which is an active component of the traditional Chinese
      medicine Gardenia jasminoides Ellis, and has been recognized as a beneficial
      compound against metabolic disorders. However, whether it can correct
      overnutrition-induced dyslipidemia is still unknown. In this study, the effects
      of GNP on attenuating hyperlipidemia and hepatic lipid accumulation were
      investigated using normal and obese mice induced with a high-fat diet (HFD) and
      primary hepatocytes treated with free fatty acids. We also sought to identify
      potential targets of GNP to mediate its effects in the liver. We found that obese
      mice treated with GNP showed a decrease in the body weight, serum lipid levels,
      as well as hepatic lipid accumulation. Besides, GNP regulated hepatic expression
      levels of lipid metabolic genes, which are important in maintaining systemic
      lipid homeostasis. At the molecular level, GNP increased the expression levels of
      miR-142a-5p, which bound to 3' untranslated region of Srebp-1c, an important
      regulator of lipogenesis, which thus led to the inhibition of lipogenesis.
      Collectively, our data demonstrated that GNP effectively antagonized HFD-induced
      hyperlipidemia and hepatic lipid accumulation in mice. Such effects were achieved
      by regulating miR-142a-5p/SREBP-1c axis.

PMID- 29197189
TI  - Incidental gallbladder cancer at cholecystectomy.
AB  - BACKGROUND: Gallbladder tumours rank fifth in the world among gastrointestinal
      system tumours. Coincidental gallbladder tumours are diagnosed during
      cholecystectomies, or by examining the cholecystectomy material. AIMS: In this
      study, we aimed to evaluate the incidence of gallbladder cancer among patients
      undergoing cholecystectomies due to gallbladder disease. STUDY DESIGN:
      Retrospective study METHODS: The files of 341 patients who had undergone routine
      cholecystectomy operations between January 2013 and March 2016 were reviewed, and
      their pathology results were recorded. Those patients with gallbladder carcinomas
      were evaluated in terms of age, gender, preoperative findings, existing symptoms,
      radiological findings, surgical findings and follow-up. The cancer invasion depth
      was classified according to the American Joint Commission on Cancer (AJCC) atlas,
      and this study was approved by the ethical committee of our university. RESULTS:
      Among the 341 patients who participated in this study, 253 (74.41%) were female,
      88 (25.80%) were male, and their average age was 49.61 years old (17-86). Seven
      of the patients (2.05%) had gallbladder tumours; six of which were female, one
      was male and their average age was 67.71 years old (62-76). One tumour was
      diagnosed as a frozen specimen during the operation, while the others were
      diagnosed during the postoperation phase. Three of the patients had T1b and four
      had T2 tumours. CONCLUSION: Gallbladder tumours detected incidentally could
      extend survival rates with proper surgical intervention and chemotherapy. The
      possibility of a tumour should not be dismissed in those patients with advanced
      age, females or patients with gallbladder stones. Frozen specimens should be
      created during a cholecystectomy, and if there is any doubt about the diagnosis,
      a postoperative histopathological examination of the gallbladder should be
      conducted. KEY WORDS: Cholecystectomy, Gall bladder stone, Incidental gallbladder
      carcinoma.

PMID- 29197190
TI  - Percutaneous treatment with radiofrequency ablation of varicose veins recurring
      after vein stripping surgery A preliminary study.
AB  - AIM: The aim of our study was to evaluate the efficacy of a new treatment of
      recurrent varicose vein after stripping of the great saphenous vein with rigid
      radiofrequency needles. MATERIAL OF STUDY: 37 patients enrolled (11 males and 26
      females). 10 patients had recurrent varicose veins for the presence of residual
      reflux in the Saphenous-Femoral Junction (SFJ) stump, whilst 21 patients for the
      presence of a single or multiple re-chanalized and refluxing perforator veins,
      and 6 had mixed rechanalization due to perforator veins and refluxing saphenous
      stump. All patients have been treated by percutaneous ultrasound-guided
      obliteration with radiofrequency needles. Treatment efficacy have been assessed
      by US evaluation, and/or the appearance of recurrent varicose veins and
      classified as REVAS questionnaire. Follow up has been carried out at 30, 60, 180
      days and 1 year after treatment. RESULTS: A complete obliteration of the
      perforator(s) stump(s) was observed in 12 procedures immediately after the
      treatment, and confirmed at 30 and 60 days. In 1 case (7.69 %) obliteration was
      not complete at 60 days. After 1 year of follow-up 3 perforators (23.07%) showed
      an incomplete or failed obliteration. A complete obliteration of the treated SFJ
      was observed in 27 cases at the end of the procedure and confirmed after 60 days
      of follow-up patients (Fig. 4). In 2 cases (6.89%), obliteration was non complete
      at 60 days. After 1 year of follow up 5 treated SFJ (17.24%) stumps showed an
      incomplete or a failed obliteration. DISCUSSION: Results show a reduction of the
      number of limbs affected by ulcer, skin pigmentation and stasis eczema,
      demonstrating correction of haemodynamic overload to be effective. CONCLUSIONS:
      This treatment is a new and effective solution to the problem of post-stripping
      recurrent varicose veins. KEY WORDS: Perforator veins, Radiofrequency, Recurrent
      post-stripping varicose veins, Saphenofemoral stump.

PMID- 29197191
TI  - Post-thyroidectomy hypoparathyroidism, what should we keep in mind?
AB  - AIM: Hypoparathyroidism and the resulting hypocalcemia is a common iatrogenic
      complication following surgical procedures to the neck, and commonly, to the
      thyroid gland. The aim of this study was to review the available literature to
      summarize current data related to the development of hypoparathyroidism after
      thyroid surgery. MATERIALS AND METHODS: An analysis of the surgical literature
      was performed using the search engine EMBASE and PubMed with particular reference
      to the principal risk factors related to the post-thyroid surgery
      hypoparathyroidism. Moreover the medical records of 345 patients, who underwent
      thyroid surgery at the Section of Endocrine Surgery - Department of Medical and
      Surgical Sciences, Advanced Technologies "G. Ingrassia" University of Catania,
      Italy, were also examined. RESULTS: The definition of hypoparathyroidism varies
      widely in literature. There is a wide range of reported incidences of transient
      and permanent postoperative hypoparathyroidism in literature. Extensive surgery,
      malignant disease and concomitant central and/or lateral neck dissection,
      autoimmune or Grave's' disease and re-operation represent the most recognized
      risk factors. A wide consensus exists about transplanting a parathyroid gland
      when it seems to be nonviable. DISCUSSION: Although many improvements have been
      done in surgical technique, hypoparathyroidism seems to be one of the most common
      complication after total thyroidectomy. In this study we discuss the diagnosis
      methods and the importance of its early prediction regardless it is transient or
      permanent. Recovery time is under discussion: some author consider a gland
      permanent injury if restoring functionality does not occur within 6 months other
      12 months. To assess the parathyroid gland function some authors have been using
      postoperative PTH level as a useful tool for predicting hypocalcemia.
      CONCLUSIONS: Many efforts are required to address the problem of a consensus on
      best define these complications. An early low PTH level after total thyroidectomy
      is associated with a high risk of permanent hypoparathyroidism and normal levels
      usually exclude long-term parathyroid glands dysfunction. However, the cost of
      the PTH assay may limit its widespread application. Despite the reassuring
      presence of new therapeutic strategies, intra-operative preservation of the
      parathyroid glands is the best prophylaxis to avoid postoperative hypocalcemia
      after total thyroidectomy. KEY WORDS: Hypoparathyroidism, Thyroid surgery.

PMID- 29197192
TI  - Laparoscopic gastric plication for the treatment of morbid obesity by using real
      time imaging of the stomach pouch.
AB  - BACKGROUND: Bariatric surgery is a continuously evolving field. Laparoscopic
      greater curvature plication is a new investigational procedure used to treat
      patients with morbid obesity. The demand for this operation from the obese
      patients is also rising. The problem is that during gastric plication the exact
      dimensions and volume of the pouch are not known so frequently it is too large or
      too tight thus compromising the results. The aim of the study was to identify the
      parameters that can improve the outcomes after this procedure. METHODS: We
      performed laparoscopic greater curvature plication in 75 obese patients during
      2013-2015. The last 25 patients underwent surgery with a modified surgical
      technique using real-time imaging of the stomach pouch. The inclusion criteria
      for the 25 patients enrolled in this case series were the usual, body mass index
      higher than 40 or higher than 35 but with comorbidities along with the option of
      the patients for laparoscopic gastric plication. The operative technique was
      enhanced by using a computerized device and special intragastric catheters during
      the procedure that permitted real-time imaging of the gastric geometry. With this
      new operative approach we obtained the desired volume of the gastric remnant and
      we avoided strictures, obstruction or irregular shape of the pouch, problems that
      otherwise could have compromised the outcomes. RESULTS: We found an increased
      excess weight loss of 55% at six month and 65% over a 12-month follow-up period
      with alleviation of comorbidities. There were no major complications (gastric
      outlet obstructions or leaks) and less minor complications (nausea and vomiting)
      than in the patients operated with classic gastric plication procedure.
      CONCLUSIONS: This study shows that in case of laparoscopic gastric plication the
      use of our modified operative technique has better outcomes than in the classical
      setting. This is a new operative approach in the bariatric literature which can
      lead to greater acceptance of gastric plication among bariatric surgeons. The
      target population is represented by the obese patients who want to obtain similar
      results to those after gastric bypass and sleeve gastrectomy but are concerned
      about removing a part of their stomach and the postoperative complications that
      may occur, especially leaks and nutritional complications. KEY WORDS: Gastric
      geometry, Laparoscopic gastric plication, Morbid obesity, Real-time imaging.

PMID- 29197193
TI  - Negative pressure therapy alone or with irrigation in the management of severe
      peritonitis.
AB  - BACKGROUND: Ogilvie was the first to publish on open abdomen (OA) for the
      treatment of the damages caused by penetrating abdominal wounds in war events.
      Research improved those devices that allow a controlled, homogeneous and
      continuous extraction of contaminated fluids from all abdominal recesses, which
      are nowadays the base of the "Open Abdomen" technique. MATERIALS AND METHODS:
      From August 2012 to February 2016 at the Department of Emergency Surgery of
      Cardarelli Hospital in Naples, 40 patients affected by Severe Peritonitis have
      been treated with OA technique. 13 (32,5%) were treated with only the suction
      drainage system, 27 patients (67,5%) were treated with suction drainage and
      irrigation system. Abthera(r) device was used in all patients. RESULTS: The
      duration of treatment was 15 days in the first group, with 7 device's
      substitutions, while in the second group it was about 10 days with 4
      substitutions At the end of the procedure we were able to perform primary fascia
      closure in 7 cases (53,8%) in the first group and in 23 cases (85.2%) in the
      second group. 4 patients (30,8%) died in the first group, and 7 (26%) in the
      second. CONCLUSION: The suction/irrigation method seems to be appropriate to use
      in case of a surgical emergency that causes severe peritonitis. It is associated
      not only with lower death rates but also with better parameters, that are more
      frequently worse during prolonged treatments. Irrigation of abdominal cavity
      causes also less retraction of fascia recti which leads to a higher rate of
      direct fascia closure. Key Words: Emergency surgery, Irrigation, Open abdomen,
      Peritonitis.

PMID- 29197194
TI  - The role of self-expandable metallic stents as "bridge to surgery" for the
      treatment of acute malignant colorectal obstruction. Our experience.
AB  - INTRODUCTION: Despite the widespread use of screening programs, the colorectal
      cancer occurs in 7-29% of cases with a bowel obstruction, needing an immediate
      decompression treatment by emergency surgery; unfortunately, the emergency
      surgery is characterized by high morbidity and mortality rates. The endoscopic
      placement of self-expandable metallic stents can be a useful alternative,
      allowing to decompress the acute obstruction in a short time, in order to correct
      dehydration, electrolytic imbalance and to improve the overall clinical
      conditions prior to adequately plan the intervention of elective surgery. AIM:
      The objective of our study was to evaluate the clinical success and potential
      complications related to the stent placement as "bridge to surgery". MATERIALS
      AND METHODS: Twenty-four patients with acute intestinal obstruction due to
      colorectal cancer were retrospectively observed in our Surgery Unit. They were
      selected only patients in whom technical success, defined as the correct
      placement of the stent, was recorded. All patients underwent a preoperative
      abdominal X-rays and whole body contrast- enhanced Computed Tomography (ceCT).
      Furthermore, an intraoperative fluoroscopy was also performed to obtain a better
      anatomical depiction of the lesions. The sites of obstruction were in the left
      colon (n=13) and in the proximal rectal tract (n=11). Covered and uncovered
      stents were placed respectively in 12 and 12 patients. The Over The Wire (OTW)
      technique has been used in 11 patients while the Through The Scope (TTS)
      technique in 13 subjects. All patients were brought to elective surgery in 5-10
      days. The clinical success was defined as the resumption of normal bowel function
      within 48-72 hours and the absence of complications. RESULTS: Technical success
      was documented in 24 patients (100%). Clinical success was recorded in 17
      patients (70.8%) while, in 7 patients, as treatment complications were recorded:
      2 stent migrations (8.3%), 2 cases with tenesmus (8.3%), 2 bleeding (8.3%), 2
      cases of abdominal pain (8.3%) and 1 case of perforation (4.2%), were recorded.
      CONCLUSION: In our series we found that placing self-expandable metallic stents,
      considered as "bridge to surgery", was a useful technique in the resolution of
      acute malignant colorectal obstructions, with high success rate and low rate of
      complications. KEY WORDS: Colorectal cancer, Clinical success, Large bowel
      obstruction, Radiology, Self-expanding metallic stent, Stenting, Surgery.

PMID- 29197195
TI  - Oxidative and Nitrosative Stress as Well as the Tryptophan Catabolites Pathway in
      Depressive Disorders.
AB  - The aim of this paper is to elucidate the role of oxidative and nitrosative
      stress as well as the tryptophan catabolites pathway in the development of
      depression and the mechanism of action of antidepressant drugs, based on the
      available literature. According to the World Health Organization (WHO), an
      estimated 350 million people worldwide suffer from depression. The pathogenesis
      of depressive disorders has not been fully explained yet and several causes of
      this disease have been suggested. There is evidence for the involvement of
      several interconnected biochemical pathways, including oxidative and nitrosative
      stress as well as the tryptophan catabolites pathway. Studies to date indicate
      that patients with depression have lower levels of enzymatic and non-enzymatic
      elements of an antioxidant response and, at the same time, they display an
      increased amount of oxidative stress markers, when compared to healthy
      individuals. The development of depression is also associated with excessive
      activity of nitric oxide synthase. Furthermore, decreased levels of tryptophan
      and increased levels of its harmful catabolites, i.e. kynurenine and quinolinic
      acid, may lead to progression of the disease. Changes in these biochemical
      pathways can be used as risk factors for the development of depression and, in
      the future, they could be utilized as diagnostic biomarkers. Moreover, regulation
      of biochemical processes may contribute to the development of a new, effective
      and personalized antidepressant therapy.

PMID- 29197196
TI  - Analysis of the Prevalence of Mental Disorders in Psoriasis: The Relevance of
      Psychiatric Assessment in Dermatology.
AB  - BACKGROUND: The boundary between Dermatology and Psychiatry has increasing
      recognition. Psoriasis is a common psychophysiological skin disease with a major
      impact on patient's quality of life and a paradigmatic example of a pathology in
      that boundary. Studies are needed to exactly point out the prevalence of specific
      psychopathology and mental disorders associated with psoriasis. This work intends
      to analyse the prevalence of psychopathology and psychiatric comorbidities in
      patients with psoriasis. METHODS: A systematic review of the literature was
      performed following the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) and the "5S" model proposed by Haynes. From all the papers
      retrieved by this search, a total of 34 papers met the inclusion criteria and
      were then deeply analysed. RESULTS: The most prevalent mental disorders in these
      patients are sleep disorders (average prevalence: 62.0%), sexual dysfunction
      (45.6%), personality (35.0%), anxiety (30.4%), adjustment (29.0%), depressive
      (27.6%) and substance-related and addictive disorders (24.8%). Other mental
      disorders have been less described, namely somatic symptoms and related
      disorders, schizophrenia and other psychoses, bipolar disorder and eating
      disorders. CONCLUSIONS: This updated research shows that the prevalence of
      psychiatric conditions in psoriasis may range from 24% to 90%. The study of the
      mind-skin connection in psoriasis may improve the knowledge about psoriasis and
      its psychiatric comorbidities. The link between psoriasis and associated mental
      disorders is frequently forgotten or not considered in the clinical practice.
      Psychiatric disorders in patients with psoriasis may be underdiagnosed. These
      patients would really benefit from psychiatric assessment, with therapeutic
      relevance.

PMID- 29197197
TI  - A Systematic Review of Tumor Necrosis Factor-alpha in Post-Traumatic Stress
      Disorder: Evidence from Human and Animal Studies.
AB  - BACKGROUND: Growing evidence suggests a pathophysiological role of cytokines in
      post-traumatic stress disorder (PTSD). Tumor necrosis factor (TNF)-alpha is a key
      cytokine. Therefore, we performed a systematic review to examine the findings
      regarding TNF-alpha derived from both animal and human studies of PTSD. METHODS:
      Using PRISMA guidelines, we reviewed relevant articles in PubMed from inception
      until 11th April 2017. Human studies that reported group comparisons and/or
      longitudinal investigations of TNF-alpha production/concentration were included.
      Research reporting on TNF-alpha levels in animal models of PTSD were also
      included. RESULTS: Twenty-seven articles were identified. Data from human cross
      sectional studies suggests that plasma/serum levels of TNF-alpha are elevated in
      those with PTSD, as compared to healthy controls. Longitudinal assessments of TNF
      alpha are limited and data are mixed. Limited data from animal studies suggest an
      increased TNF-alpha production in the hippocampus of rats following stress, which
      can be reversed by immunomodulatory drugs. CONCLUSIONS: Our findings suggest TNF
      alpha may be a potential biomarker and treatment target for PTSD. Findings need
      to be considered in light of heterogeneous methods for measurement and analysis
      of TNF-alpha concentration. Longitudinal research is needed to understand the
      role of TNF-alpha in the development and/or maintenance of PTSD.

PMID- 29197198
TI  - Cardiovascular Disease Risk Factors in Patients with Posttraumatic Stress
      Disorder (PTSD): A Narrative Review.
AB  - Posttraumatic stress disorder (PTSD) is a chronic condition related to severe
      stress and trauma. There is a mounting evidence about increased prevalence and
      mortality from cardiovascular diseases (CVD) in patients with PTSD. This review
      summarizes the current data on possible relations between PTSD and increased
      risks of CVD, including biological, psychological and behavioral factors.
      Biological factors refer to increased prevalence of metabolic syndrome (MetS),
      hypertension, elevation of pro-inflammatory cytokines and homocysteine levels.
      Peripheral Brain-derived neurotropic factor (BDNF), serum N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and quantitative electroencephalogram (qEEG) are
      promising surrogate markers of increased cardiovascular risk. Among psychological
      factors, some personality traits, such as neuroticism and trait
      impulsivity/hostility, contribute to the development of PTSD, and are associated
      with general cardiovascular distress. Recently, type-D (distressed) personality
      is usually investigated in relation to cardiovascular morbidity, but in
      populations other than PTSD patients. Behavioral factors refer to unhealthy life
      styles, encompassing high smoking rate, drug substances abuse and addiction,
      physical inactivity and unhealthy diet. The relationships among all these factors
      are complex and yet incompletely taken into consideration. Because of a high
      prevalence of CVD in patients with PTSD, there is a strong need for a more
      intensive focus on this vulnerable population in both primary and secondary
      cardiovascular prevention as well as in effective treatment possibilities.

PMID- 29197199
TI  - Elevated Serum C-Reactive Protein Level Is not Associated with Serum Nitric Oxide
      in Patients with Posttraumatic Stress Disorder.
AB  - BACKGROUND: The aim of the present study was to evaluate serum nitric oxide (NO)
      and C reactive protein (CRP) concentration in veterans with and without PTSD.
      Furthermore, we aimed to assess whether there is a correlation between serum NO
      and CRP concentrations in tested groups. SUBJECTS AND METHODS: Cross-sectional
      study included 90 male individuals, with and without experience of direct war
      combat, divided into three equal groups (n=30): group 1- included war veterans
      with PTSD, group 2 - included war veterans without PTSD, and control group - 30
      apparently healthy volunteers, without experience of direct war combat. The
      diagnosis of PTSD was assessed according to the guidelines in the 10th revision
      of the International Classification of Diseases (ICD-10). High-sensitivity CRP
      was determined by immunonephelometry. The serum NO level was determined by
      classic colorimetrical Griess reaction. RESULTS: Serum CRP concentration in
      veterans with (3.54+/-1.19 mg/L) and without PTSD (3.24+/-2.04 mg/L), was
      significantly higher (p<0.05) compared to control group (1.26+/-1.06 mg/L). Serum
      NO concentration in veterans with (7.64+/-4.43 MUmol/L) and without PTSD (7.12+/
      2.60 MUmol/L) was significantly lower (p<0.05) compared to control group (11.26+/
      7.01 MUmol/L). Statistically significant correlation between serum NO and CRP
      concentration was determined in veterans without PTSD (r=-0.473; p<0.01). No
      correlation was observed between serum NO and CRP concentration in veterans with
      PTSD (r=0.118; p=0.534) and in control group (r=-0.067; p=0.727). CONCLUSION: The
      present study has showed significant increase of serum CRP and significant
      decrease of serum NO concentrations in veterans with and without PTSD.
      Furthermore, statistically significant negative correlation between serum NO and
      CRP concentration was determined only in veterans without PTSD. Obtained results
      indicate that the complex mechanism of the pathogenesis of PTSD requires further
      research.

PMID- 29197200
TI  - Conscious attention defect and inhibitory control deficit in Parkinson's Disease
      Mild Cognitive Impairment: A comparison study with Amnestic Mild Cognitive
      Impairment multiple domain.
AB  - BACKGROUND: Frontal/executive dysfunction commonly occurs in Parkinso's disease -
      Mild Cognitive Impairment (PD-MCI patients). However, to date, the number of
      studies comparing PD-MCI and MCI patients of other etiologies are too small. The
      present study aims at clarifying the attention/working memory and executive
      dysfunction of PD-MCI patients in comparison to amnestic MCI multiple domain
      patients with first extended then abbreviated structural brain changes suggesting
      preclinical Alzheimer's Disease. SUBJECTS AND METHODS: 40 PD-MCI patients and 40
      amnestic MCI multiple domain (aMCI+) patients were diagnosed according to the
      International guidelines. 22 healthy subjects were also recruited as control
      group. The groups were assessed by a wide neuropsychological battery, including
      measures of attention/working memory (Digit Span and Stroop Test), executive
      functions (Tower of London-Drexel Version -TOLDX- and Brixton Test), language
      (Boston Naming Test and Category Fluency), memory (Prose Recall and Pairs
      Associates Learning), and visuospatial function (Street's Completion Test and
      Constructive Apraxia Test). Performances were compared by non parametric tests.
      Spearman correlations were performed to explore association between
      neuropsychological measures of attention/working memory and executive functions
      in PD-MCI group. RESULTS: The PD-MCI patients performed worse on Digit Span and
      Stroop Interference/Error than aMCI+ and controls. AMCI+ patients, in turn,
      showed a greater deficit on TOLDX Initiation Time and on Violation Time than PD
      MCI and controls. Both PD-MCI and aMCI+ patients reported lower scores on Stroop
      Interference/Time than controls. Moreover, aMCI+ patients performed worse then
      controls on Brixton Test. Positive correlations between Digit Span and Stroop
      Interference/Error, Stroop Interference/Error and TOLDX Execution Time, Total
      Time and Violation Time, Stroop Interference Time and TOLDX Move Score and Total
      Time were found in PD-MCI group. CONCLUSION: PD-MCI patients mainly present a
      conscious attention defect and an inhibitory control deficit than aMCI+. PD-MCI
      patients with deficits in attention/working memory domain should undergo specific
      cognitive trainings in order to improve cognitive abilities and prevent
      Parkinson's Disease Dementia onset.

PMID- 29197201
TI  - Negative and helpful statements in a patient only or therapist guided internet
      forum in the aftercare for psychosomatic inpatients.
AB  - BACKGROUND: The aftercare of patients in the wake of inpatient treatment is a
      therapeutic challenge. Aim of the present study was to investigate the
      utilization, and positive or negative interactions in a patient only (PF) and a
      therapist guided internet forum (TF) in the follow up of psychosomatic inpatient
      treatment. SUBJECTS AND METHODS: After discharge from hospital, patients were
      offered to participate in a PF or TF. The rate and duration of participation was
      monitored and the content of communication classified by content analysis.
      RESULTS: In the PF 144 (8.0%) and in TF 76 (8.5%) of invited patients registered.
      Participants were somewhat younger, more often male, and professionally better
      qualified. Time of participation was 51 (sd 90) days in the PF and 59 (sd 69) in
      the TF. 32% of the registered patients wrote messages in the PF and 43% in the
      TF, with 7 (sd 10) comments on average in the PF and 15 (sd 26) in the TF. Most
      comments were health related and positive, with a higher rate in the TF. There
      were still 8 destructive comments in both forums. CONCLUSIONS: The rate of
      participation in the aftercare internet forum is low. Therapeutic guidance
      increases the rate of patient contributions. Most comments are supportive, but
      negative interactions occur even in the presence of a moderator.

PMID- 29197202
TI  - Factor structure and cut-off scores of the Hospital Anxiety and Depression scale
      (HADS) in a Croatian sample of adult patients suffering from advanced cancer.
AB  - BACKGROUND: Patients with cancer should be systematically screened for
      psychological problems at key points in their pathway. Usage of self-report
      scales for measuring anxiety and depression (such as Hospital Anxiety and
      Depression scale (HADS)) is a very practical methodfor detecting anxiety and
      depression. The aim of this research was to determine latent structure,
      reliability and cut-off scores of HADSin a Croatian sample of adult patients
      suffering from advanced metastatic cancer. SUBJECTS AND METHODS: According to
      inclusion and exclusion criteria, participant were recruited at University
      Hospital Centre Zagreb (N=46; January 2015) and Clinical Hospital Centre 'Sisters
      of Mercy' (N=29; April 2015). All participants underwent short structured
      psychodiagnostic interview, cognitive evaluation (usingMontreal Cognitive
      Assessment (MoCA) test) and were given HADS. RESULTS: When using PCA separately
      for the items of each original scale of HADS, only four items for the component
      Depression satisfactorily saturate principal component and when using PCA for all
      the items, only seven items from the original scale satisfactorily saturate
      unique principal component. Maximum Likelihood extraction method showed that only
      four items from the original scale satisfactorily saturated the theoretical
      scales. CONCLUSIONS: The results show that the best solution to use HADS, in
      defined Croatian population, is as one-dimensional screening instrument
      (Cronbach's alpha coefficient of internal consistency=0.774) with cut-off score
      11/12.

PMID- 29197203
TI  - Positive impact of prescribed physical activity on symptoms of schizophrenia:
      randomized clinical trial.
AB  - BACKGROUND: The purpose of this study was to examine functional capacity of
      cardio-respiratory system in patients with schizophrenia, and to evaluate the
      effects of 12 weeks prescribed physical activity on aerobic capacity and symptoms
      of schizophrenia. SUBJECTS AND METHODS: Study involved 80 hospitalized patients
      with any of the subtypes of schizophrenia (42 men, 38 women). They were divided
      into two groups: exercise and control group, both with 40 patients. Maximal
      aerobic capacity (VO2 max) as an indicator of cardiovascular fitness has been
      obtained by cardiopulmonary stress test on a treadmill. Twelve weeks program of
      prescribed physical activity (45 minutes, four times per week) was made for every
      patient individually. Patients in exercise group practiced in training zone
      between 65 and 75% of their maximum heart rate (HR). Target HR was controlled by
      Polar F4 monitors. Symptoms of schizophrenia were measured by using Positive and
      Negative Symptoms Scale (PANSS). RESULTS: Before the exercise program was
      introduced, measured VO2 max was significantly lower in patients with
      schizophrenia, than the expected average value in matched healthy subjects
      (p<0.001). After twelve weeks, patients in exercise group showed a significant
      increase of VO2max (p=0.002), and significantly higher level of VO2max compared
      to the control group (p=0.000). Significant differences were also observed on
      PANSS general psychopathology subscale (p=0.007) and on PANSS total score
      (p=0.001). The pharmacotherapy and exercise had influence on PANSS general
      psychopathology (p=0.002) and PANSS total score (p=0.001). CONCLUSIONS:
      Individuals with schizophrenia have lower levels of aerobic capacity compared to
      general population. Prescribed physical activity significantly improves aerobic
      capacity in people with schizophrenia and it is effective in amelioration of some
      psychiatric symptoms. Prescribed physical activity could be an effective
      adjunctive treatment for patients with schizophrenia, not only for prevention and
      treatment of comorbidities, but also having an impact on symptoms of
      schizophrenia.

PMID- 29197204
TI  - Effect of HBM Rehabilitation Exercises on Depression, Anxiety and Health Belief
      in Elderly Patients with Osteoporotic Fracture.
AB  - BACKGROUND: Guided by the health belief model (HBM), this study provided elderly
      patients with osteoporotic fracture with health education concerning osteoporosis
      (OP) prevention, carried out rehabilitation exercises based on HBM, and evaluated
      the intervention effect of HBM rehabilitation exercises, to offer a scientific
      basis for improving the prognosis of elderly patients with OP fracture. SUBJECTS
      AND METHODS: A total of 162 elderly patients with OP fracture treated in three
      third-grade general hospitals of Jiangsu Province from January 2016 to September
      2016 participated in this study. According to the minimization random allocation
      method, the patients were divided into two groups: the conventional
      rehabilitation group and the HBM rehabilitation group, with 81 patients in each
      group. After three months of intervention, the two groups were compared in terms
      of anxiety, depression, OP knowledge, and OP health belief. RESULTS: After 3
      months of intervention, the anxiety and depression scores decreased in both
      groups. Both anxiety and depression scores of the HBM rehabilitation group were
      higher than those of the conventional rehabilitation group, with statistically
      significant differences (P<0.001). The increases in the OP knowledge score and OP
      health belief score of the HBM rehabilitation group were higher than those of the
      conventional rehabilitation group, with statistically significant differences
      (P<0.001). CONCLUSIONS: HBM-based rehabilitation exercises alleviate negative
      emotions in elderly patients with osteoporotic fracture and improve their OP
      knowledge and health belief scores.

PMID- 29197205
TI  - The impact of anxiety sensitivity on suicidality in adolescents with major
      depressive disorder.
AB  - BACKGROUND: Few studies have examined the link between anxiety sensitivity (AS)
      and suicidality among adolescents with major depressive disorder; thus, there is
      a need to explore this relationship in order to fill the research gap. The aim of
      this cross-sectional study was to examine the association among AS and suicidal
      behaviour while taking into account the effects of potential third variables such
      as the presence of anxiety disorders and hopelessness in adolescents with major
      depressive disorder. SUBJECTS AND METHODS: Participants (n=101) completed self
      report measures of depressive symptoms, AS, hopelessness and suicidal ideation
      severity. The presence of anxiety disorders and suicide attempt history were
      determined with psychiatric interviews. The association between psychiatric
      variables was evaluated using structural equation modelling. RESULTS: Results
      showed that AS cognitive concerns had a positive effect on suicidal ideation
      mediated by the severity of depression. AS physical concerns had a negative
      direct effect on suicidal ideation, but there was also a positive relationship
      among these variables through hopelessness, thus, the total effect of AS physical
      concerns was not significant. There were also positive relationships between
      hopelessness and suicidal ideation, and the presence of anxiety disorders to
      suicide attempt history. CONCLUSIONS: The results of this study suggest that
      higher AS cognitive concerns may be a risk factor for suicidality through the
      severity of depression in adolescents who are diagnosed with major depressive
      disorder.

PMID- 29197206
TI  - Characteristics and Development of Nonsuicidal Super Self-Injury among Borderline
      Inpatients.
AB  - BACKGROUND: Nonsuicidal self-injury (NSSI) is a key feature of borderline
      personality disorder (BPD), which is strongly associated with childhood
      traumatization. To the best of our knowledge, there has been a lack of studies
      investigating extensively the characteristics of borderline patients who engage
      in extremely high numbers of NSSI, and their features of NSSI, trauma history and
      psychopathology. The aim of this study is to identify groups of borderline
      inpatients on the basis of the lifetime number of NSSI, and to explore the
      characteristics of these groups regarding the onset, reasons and methods of NSSI,
      history of childhood traumatization, and severity of psychopathology. SUBJECTS
      AND METHODS: 80 psychiatric inpatients with BPD were included in the study, of
      whom 63 had a history of NSSI and 17 had not. The frequency and characteristics
      of NSSI were assessed by the Ottawa Self-Injury Inventory and the childhood
      traumatization were assessed by the Traumatic Antecedents Questionnaire and the
      Early Trauma Inventory. RESULTS: In this study among self-injuring borderline
      inpatients a super self-injuring group was identified, who engaged in extremely
      high numbers of NSSI (75.0+/-28.4 acts/lifetime). Compared to moderate self
      injurers, super self-injurers began harming themselves at a younger age
      (p=0.008), used more severe forms of NSSI, and all of them reported an anti
      dissociation function of NSSI. Adverse childhood experiences were more prevalent
      in the super self-injuring group. The strongest predictors of the lifetime number
      of NSSI were early sexual abuse (p<0.001), intrafamilial physical abuse
      (p<0.001), a higher cumulative trauma score (p=0.030) and a greater number of BPD
      criteria (p<0.001). CONCLUSIONS: Our results suggest that the frequency of NSSI
      in borderline inpatients can be seen as an indicator of clinically-relevant
      anamnestic data, namely, of the severity, complexity and onset of childhood
      traumatization, and of the severity of current borderline psychopathology.

PMID- 29197207
TI  - Correlates of Involuntary Admission: Findings from an Italian Inpatient
      Psychiatric Unit.
AB  - BACKGROUND: Involuntary admission is challenging in terms of providing the most
      effective but least restrictive care in accordance with the country's
      regulations. A better understanding of correlates of voluntary versus involuntary
      admission legal status is crucial to improve clinical decision-making and
      effectiveness of the overall mental health care system. SUBJECTS AND METHODS: We
      collected chart-review data pertaining to 848 patients, discharged between June
      2011 and June 2014, from an Italian inpatient psychiatric unit. Diverse
      sociodemographic and clinical variables were collected. Bivariate analyses and
      binary logistic regression were performed to examine correlates of involuntary
      admission. RESULTS: Bivariate analyses showed that involuntary status was related
      to: the reason for hospitalization, not being on psychiatric medications at
      admission, and being admitted from another inpatient ward (in particular, from
      the emergency department). The final regression model identified four main
      variables independently associated with legal status: being admitted for
      psychotic features, suicidal behavior, or impulsive behavior, and not being on
      medication at admission (Nagelkerke pseudo R2=0.15, p<0.001). A strong
      association with length of stay was also documented. CONCLUSIONS: Understanding
      the causes and consequences of involuntary admission will enhance the field's
      understanding of how to provide the most effective, but least restrictive,
      psychiatric care.

PMID- 29197208
TI  - Occurrence of post-injection delirium/sedation syndrome after application of
      olanzapine long-acting injection during one year period.
AB  - INTRODUCTION: The aim was to report the occurrence of after application of
      olanzapine long-acting injection (OLAI) in patients with schizophrenia during one
      year period. SUBJECTS AND METHODS: During one year period, OLAI was applied to 30
      patients with schizophrenia (18 men, 12 women) who were non-adherent to previous
      treatment with oral olanzapine. Patients were 20-58 years of age (39 years old on
      average), diagnosed with SCID based on DSM-IV-TR criteria. Patients received OLAI
      in dosage between 210-405 mg (287+/-62 (mean +/- SD)) every 2-4 weeks. RESULTS:
      Out of 30 patients that received OLAI, 29 patients improved significantly without
      side-effects, and one patient developed post-injection delirium/sedation syndrome
      (PDSS). The patient's somatic condition stabilized and treatment with OLAI was
      discontinued due to the PDSS. CONCLUSION: The occurrence of PDSS is not common
      and when it occurs, in our experience, it was reversible.

PMID- 29197209
TI  - Cotard Syndrome in Hypoactive Delirium - A Case Report.

PMID- 29197210
TI  - Trichobezoar Ventriculi in 7-Year Old Girl - Case Report.

PMID- 29197211
TI  - Change of the Writing-Hand: Unusual Manifestation of Hallervorden-Spatz Disease.

PMID- 29197212
TI  - Recurrent Transitory Ischemic Attacks with Subsequent Development of the Ischemic
      Stroke as Initial Manifestation of Eosinophilic Granulomatosis with Polyangiitis
      in Depressed Patient.

PMID- 29197213
TI  - [Sudden Crisis in Dementia].
AB  - If we're thinking about Dementia, we normally don't think about a sudden crisis.
      Dementia is a slowly creeping illness, which causes a loss of memory. In addition
      to this loss of cognitive functions, there is also the death of neural cells,
      which in turn leads to completely different symptoms. This leads to the
      appearance of BPSD (Behavioural and psychotic symptoms of dementia). There are
      guides to the therapy of cognitive deficits of dementia in existence, to use them
      within the EbM criteria. There exists only a little bit of information on the
      therapy of BPSD. Therefore I will talk in his article mainly about possibilities
      of therapy, that were found through medical experience. For those possibilities
      is only little evidence and are mostly off label, because the field of dementia
      patients has almost no studies, except pharmaceutical ones. The cause for this
      lack of studies is probably found in the huge Workload by the ethic commission of
      every study, which are today the norm for every single study. So please take my
      work as a foundation for discussion, though which you search for the most optimal
      solution for the individual problem of your patient.

PMID- 29197214
TI  - Nonsuicidal self-injury in a naturalistic sample of adolescents undergoing
      inpatient psychiatric treatment: prevalence, gender distribution and
      comorbidities.
AB  - BACKGROUND: A growing body of research points toward nonsuicidal self-injury
      (NSSI) in adolescents as an important and frequent health-related risk factor. In
      2013, NSSI was proposed in section 3 of the DSM-5 as a new diagnostic entity
      warranting further study. In line with that goal, the present study was conducted
      in order to evaluate prevalence, gender distribution and comorbidities of NSSI in
      a sample of adolescent psychiatric inpatients. SUBJECTS AND METHODS: The study
      included 130 adolescents (mean age 15.09 years, SD +/- 1.47; 71.5% female)
      undergoing inpatient psychiatric treatment at a specialized facility. The factors
      assessed were sociodemographic data, the presence of NSSI according to the
      proposed DSM-5 criteria, clinical psychiatric diagnosis, the presence of
      suicidality and the presence of personality disorder. RESULTS: A large
      percentage, 38.5%, of the sample fulfilled DSM-5 criteria for NSSI, and more than
      half (50.8%) of the adolescents indicated having injured themselves at least once
      in the past. Patients with NSSI were predominantly young women and clustered in a
      spectrum of diagnostic entities including not only borderline personality
      disorders but also substance use disorders and affective disorders. A strong
      association was found between suicidality (suicidal ideation, history of suicide
      attempt) and NSSI. CONCLUSIONS: In line with previous findings, NSSI among
      adolescent psychiatric inpatients was found to be a frequent phenomenon
      associated with a broad spectrum of comorbidities. Moreover, while NSSI is
      conceptualized as an act without suicidal intent, it commonly occurs in patient
      groups with suicidal ideation or with a history of suicide attempts.

PMID- 29197215
TI  - [Crisis Interventions in Acute Emergency Situations].
AB  - In the article about crisis intervention after incriminating events, I start by
      explaining the specific terms, since in recent years different terms have been
      used, which have repeatedly caused uncertainty. How might people react to extreme
      stress and what are factors of protection and risk? Further I will explain the
      effect of psychosocial support as well as the structure and forms of
      interventions. The basic principles of interventions and the 10 essential
      intervention steps are described. In order to be able to provide targeted
      assistance, it is necessary for the psychosocial emergency aid staff to know
      about the experience of those affected in acute emergency situations. In order to
      ensure that psychosocial emergency helpers are able to recover from their
      missions or taking care of those affected, it is necessary to know the risks and
      take them into account while planning the auxiliary structure.

PMID- 29197217
TI  - RPTEC/TERT1 cells form highly differentiated tubules when cultured in a 3D
      matrix.
AB  - The proximal tubule is the primary site for renal solute reabsorption and
      secretion and thus a main target for drug-induced toxicity. Current nonclinical
      methods using 2D cell cultures are unable to fully recapitulate clinical drug
      responses mainly due to limited in vitro functional lifespan. Since extracellular
      matrices are known to be key regulators of cell development, culturing cells on
      classic 2D plastic surfaces inevitably results in loss of differentiation. Hence,
      3D models of the human proximal tubule that recapitulate the in vivo morphology
      would allow for improved drug screening and disease modeling. Here, the
      development and characterization of a 3D proximal tubule model using RPTEC/TERT1
      cells is presented. RPTEC/TERT1 cells self-assembled in matrigel to form highly
      differentiated and stable 3D tubular structures characterized by a branched
      network of monolayered cells encircling a cell-free lumen thus mimicking the
      proximal tubule. In vitro tubuli resembled the polarity of a proximal tubule
      epithelium as indicated by polar expression of Na+/K+- ATPase and ZO-3.
      Furthermore, 3D cultured RPTEC/TERT1 cells showed overall increased mRNA
      expression of xenobiotic transporters e.g. OCTs and MATEs and de novo expression
      of OAT3 when compared to cultures on plastics or membrane inserts. Finally, this
      model was used to assess delayed cisplatin-induced nephrotoxicity and
      demonstrated increased sensitivity when compared to 2D culture. Thus, the easy-to
      use model described here may prove to be useful for mechanistic investigations,
      e.g. in discovery of compounds interfering with tubule formation, differentiation
      and polarization, as well for the detection and understanding of pharmaceutical
      induced nephrotoxicity.

PMID- 29197216
TI  - Early Cognitive, Structural, and Microstructural Changes in Presymptomatic
      C9orf72 Carriers Younger Than 40 Years.
AB  - Importance: Presymptomatic carriers of chromosome 9 open reading frame 72
      (C9orf72) mutation, the most frequent genetic cause of frontotemporal lobar
      degeneration and amyotrophic lateral sclerosis, represent the optimal target
      population for the development of disease-modifying drugs. Preclinical biomarkers
      are needed to monitor the effect of therapeutic interventions in this population.
      Objectives: To assess the occurrence of cognitive, structural, and
      microstructural changes in presymptomatic C9orf72 carriers. Design, Setting, and
      Participants: The PREV-DEMALS study is a prospective, multicenter, observational
      study of first-degree relatives of individuals carrying the C9orf72 mutation.
      Eighty-four participants entered the study between October 2015 and April 2017;
      80 (95%) were included in cross-sectional analyses of baseline data. All
      participants underwent neuropsychological testing and magnetic resonance imaging;
      63 (79%) underwent diffusion tensor magnetic resonance imaging. Gray matter
      volumes and diffusion tensor imaging metrics were calculated within regions of
      interest. Anatomical and microstructural differences between individuals who
      carried the C9orf72 mutation (C9+) and those who did not carry the C9orf72
      mutation (C9-) were assessed using linear mixed-effects models. Data were
      analyzed from October 2015 to April 2017. Main Outcomes and Measures: Differences
      in neuropsychological scores, gray matter volume, and white matter integrity
      between C9+ and C9- individuals. Results: Of the 80 included participants, there
      were 41 C9+ individuals (24 [59%] female; mean [SD] age, 39.8 [11.1] years) and
      39 C9- individuals (24 [62%] female; mean [SD] age, 45.2 [13.9] years). Compared
      with C9- individuals, C9+ individuals had lower mean (SD) praxis scores (163.4
      [6.1] vs 165.3 [5.9]; P = .01) and intransitive gesture scores (34.9 [1.6] vs
      35.7 [1.5]; P = .004), atrophy in 8 cortical regions of interest and in the right
      thalamus, and white matter alterations in 8 tracts. When restricting the analyses
      to participants younger than 40 years, compared with C9- individuals, C9+
      individuals had lower praxis scores and intransitive gesture scores, atrophy in 4
      cortical regions of interest and in the right thalamus, and white matter
      alterations in 2 tracts. Conclusions and Relevance: Cognitive, structural, and
      microstructural alterations are detectable in young C9+ individuals. Early and
      subtle praxis alterations, underpinned by focal atrophy of the left supramarginal
      gyrus, may represent an early and nonevolving phenotype related to
      neurodevelopmental effects of C9orf72 mutation. White matter alterations reflect
      the future phenotype of frontotemporal lobar degeneration/amyotrophic lateral
      sclerosis, while atrophy appears more diffuse. Our results contribute to a better
      understanding of the preclinical phase of C9orf72 disease and of the respective
      contribution of magnetic resonance biomarkers. Trial Registration:
      clinicaltrials.gov Identifier: NCT02590276.

PMID- 29197218
TI  - The effect of electro-acupuncture on pro-oxidant antioxidant balance values in
      overweight and obese subjects: a randomized controlled trial study.
AB  - Objective To undertake a randomized controlled trial in 196 obese subjects to
      examine the effect of electro-acupuncture on serum pro-oxidant antioxidant
      balance (PAB) values. Methods Subjects received authentic acupuncture (cases) or
      sham acupuncture (controls) for 6 weeks in combination with a low-calorie diet.
      In the following 6 weeks, they received the low-calorie diet alone. Serum PAB was
      measured at baseline, and 6 and 12 weeks later. Results We found that serum PAB
      values decreased significantly in the group receiving the authentic acupuncture
      compared to the sham treatment (p<0.001) at week 6, and whilst serum PAB
      increased significantly (p<0.05) in the second phase of the study, a significant
      difference between two groups remained at 12 weeks (p<0.05). Conclusions Electro
      acupuncture in combination with a low-calorie diet was more effective at reducing
      serum PAB values in obese subjects compared to diet alone. Further work is
      required to determine the mechanism by which electro-acupuncture has this effect.

PMID- 29197219
TI  - Growth response to growth hormone treatment in patients with SHOX deficiency can
      be predicted by the Cologne prediction model.
AB  - : Background Growth hormone (GH) treatment in children with short stature
      homeobox-containing gene (SHOX) deficiency is recognized to increase height
      velocity (HV) and adult height. Prediction of growth response continues to be a
      challenge. A comparatively accurate method is the Cologne prediction model
      developed in children with GH deficiency. The aim was to investigate whether this
      model also applies to patients with SHOX deficiency. Methods Included were 48
      patients with SHOX deficiency confirmed by DNA analysis and treated with 0.05
      mg/kg/day of somatropin. Prediction by the Cologne model uses the following
      variables: relative bone age (BA) retardation, baseline insulin-like growth
      factor-I (IGF-I), urinary deoxypyridinoline (DPD) cross-links at 4 weeks and HV
      at 3 months. Results HV and height standard deviation scores (SDS) increased
      significantly during the first year of treatment. Predicted and observed HV
      (cm/year) showed a Pearson correlation coefficient of 0.50 (p<0.001; root-mean
      square error=1.63) and for first-year change in height SDS a Pearson correlation
      coefficient of 0.751 (p<0.001; root-mean-square error=0.32). Poor response could
      be adequately predicted using SDS change, with sensitivity and specificity both
      above 70% for certain thresholds. CONCLUSIONS: The results demonstrate that the
      Cologne model can be used to predict growth response in patients with SHOX
      deficiency with reasonable precision in the first treatment year, comparable to
      prediction in patients with GH deficiency.

PMID- 29197220
TI  - Allergic and non-allergic skin reactions associated with growth hormone therapy:
      elucidation of causative agents.
AB  - BACKGROUND: Allergic and non-allergic skin reactions to recombinant human growth
      hormone (rhGH) are uncommon and infrequently reported. However, physicians should
      be aware of these potential side effects to determine whether the reactions
      constitute true allergies and how to proceed with growth hormone therapy. To
      review allergic and non-allergic skin reactions caused by rhGH and subsequent
      diagnostic workup and management options. CASE PRESENTATION: We report the case
      of a 12-year-old healthy male presenting with idiopathic short stature. He
      developed an itchy skin rash over the chest and abdomen, 15 min after
      administration of the first dose of rhGH, leading us to review allergic and non
      allergic skin reactions to rhGH. In our patient, an immediate skin reaction after
      administration of rhGH prompted a concern about a type I hypersensitivity
      reaction (HS) and the discontinuation of rhGH. However, after a dermatologic
      evaluation and observed administration of rhGH without subsequent rash, the
      initial eruption was likely an exacerbation of his underlying atopic dermatitis
      and a type I HS was felt to be unlikely. The rhGH was resumed and he has been on
      rhGH for the past 1 year with no recurrence of rash and with improvement in
      growth velocity. CONCLUSIONS: Though rare, allergic and non-allergic skin
      reactions are known to occur with rhGH. It is important to know if the allergic
      reaction was due to the growth hormone molecule or one of the preservatives. It
      is also important to consider a non-allergic reaction due to flare up of
      underlying skin disorders as in our patient.

PMID- 29197221
TI  - miRNA-21 Expression in the Serum of Elderly Patients with Acute Myocardial
      Infarction.
AB  - BACKGROUND The aims of this study were to examine the expression of miRNA-21 in
      the serum of elderly patients (>65 years) with acute myocardial infarction (AMI)
      and to investigate the potential role of serum miRNA-21 as a marker of early
      cardiac myocyte damage. MATERIAL AND METHODS Thirty-eight elderly patients with
      recent AMI, 27 elderly patients with unstable angina pectoris, and 25 healthy
      elderly individuals were included in the study. Serum miRNA-21 expression was
      determined following total RNA extraction and reverse-transcribed into cDNA,
      followed by reverse transcription-polymerase chain reaction (RT-PCR). Serum
      creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (cTnI) levels were
      analyzed by electrochemiluminescence. Apoptosis of human cardiac myocytes (HCM)
      was analyzed using fluorescence-activated cell sorting (FACS), and protein
      expression of caspase-3 was detected using Western blot. RESULTS Expression
      levels of miRNA-21 in the serum of elderly patients with AMI were positively
      correlated with serum levels of CK-MB (r=0.3683, P=0.0229) and cTnI (r=0.5128,
      P=0.009). Following tumor necrosis factor (TNF)-alpha induction, the apoptosis
      rates of HCM transfected with the miRNA-21 mimic short hairpin RNA (shRNA) were
      downregulated by 39.1% compared with control HCM cells, and protein expression of
      c-Jun N-terminal kinases (JNK) and p38 were unchanged (P>0.05); protein
      expression of p-JNK, p-p38 and caspase-3 were downregulated by 37.1%, 35.8%, and
      36.0%, respectively. CONCLUSIONS Expression of miRNA-21 was upregulated in the
      serum of elderly patients with AMI, which inhibited TNF-a induced apoptosis in
      HCM by activating the JNK/p38/caspase-3 signaling pathway.

PMID- 29197222
TI  - Development and implementation of a community health survey for public health
      accreditation: Case study from a rural county in California.
AB  - OBJECTIVE: To describe the planning, development, pilot testing, fielding, and
      outcomes of a community health survey in a rural California county pursuing
      public health accreditation. DESIGN: Community partners helped the local health
      department develop the community health survey. Extensive English- and Spanish
      language pilot testing was conducted over a period of four months. Final survey
      fielding was conducted online and at 20 community sites. RESULTS: 2189 completed
      surveys were collected. Total costs for developing and fielding the survey were
      approximately $25,000. Survey results indicated that alcoholism/drug abuse,
      breathing problems, and obesity were the primary health concerns of county
      residents. Benefits of conducting the community survey included strengthening
      inter-organizational partnerships between community partners, engaging a large
      and diverse respondent sample, and gathering information on a nuanced set of
      health indicators. Challenges included an unexpectedly high number of respondents
      and managing the needs of respondents with disabilities or poor literacy.
      CONCLUSION: The information gathered from the community health survey was used in
      the implementation of a county-wide multi-agency strategic plan to address health
      priorities identified in the CHA. Engaging a broad set of community partners
      throughout the survey process was critical for ensuring the project's relevance
      and long-term regional impact.

PMID- 29197223
TI  - Does soft really matter? Differentiation of induced pluripotent stem cells into
      mesenchymal stromal cells is not influenced by soft hydrogels.
AB  - Induced pluripotent stem cells (iPSCs) can be differentiated toward mesenchymal
      stromal cells (MSCs), but this transition remains incomplete. It has been
      suggested that matrix elasticity directs cell-fate decisions. Therefore, we
      followed the hypothesis that differentiation of primary MSCs and generation of
      iPSC-derived MSCs (iMSCs) is supported by a soft matrix of human platelet lysate
      (hPL-gel). We demonstrate that this fibrin-based hydrogel supports growth of
      primary MSCs with pronounced deposition of extracellular matrix, albeit it hardly
      impacts on gene expression profiles or in vitro differentiation of MSCs.
      Furthermore, iPSCs can be effectively differentiated toward MSC-like cells on the
      hydrogel. Unexpectedly, this complex differentiation process is not affected by
      the substrate: iMSCs generated on tissue culture plastic (TCP) or hPL-gel have
      the same morphology, immunophenotype, differentiation potential, and gene
      expression profiles. Moreover, global DNA methylation patterns are essentially
      identical in iMSCs generated on TCP or hPL-gel, indicating that they are
      epigenetically alike. Taken together, hPL-gel provides a powerful matrix that
      supports growth and differentiation of primary MSCs and iMSCs - but this soft
      hydrogel does not impact on lineage-specific differentiation.

PMID- 29197224
TI  - Variations in the number of births by day of the week, and morbidity and
      mortality in very-low-birth-weight infants.
AB  - OBJECTIVE: To know the distribution of births of very low birth weight infants by
      day of the week, and whether this distribution affects the morbidity and
      mortality in this group of patients. METHODS: This was a retrospective analysis
      of data collected prospectively in the Spanish SEN1500 network (2002-2011).
      Outborn infants, patients with major congenital anomalies, and those who died in
      the delivery room were excluded. Births were grouped into "weekdays" and
      "weekends." A multivariate logistic regression analysis was conducted to evaluate
      the independent effect of the birth moment on outcomes, and Cox regression for
      survival. RESULTS: Out of a total of 27,205 very low birth weight infants born at
      and/or admitted to the participating centers, 22,961 (84.4%) met inclusion
      criteria. A reduction of 24% in the number of births was observed during the
      "weekends" compared with "weekdays". In the raw analysis, patients born on
      weekends exhibited higher morbidity and mortality (mortality rate: 14.2% vs.
      16.5%, p<0.001), but differences were no longer significant after adjusting for
      confounding factors. CONCLUSIONS: The present results suggest that current care
      practices reduce the proportion of births during the weekends and tend to cluster
      some high-risk births during this period, increasing crude morbidity and
      mortality. However, after adjusting for confounding factors, the differences
      disappear, suggesting that overall care coverage in these centers is appropriate.

PMID- 29197225
TI  - 4-Aminopyridine based amide derivatives as dual inhibitors of tissue non-specific
      alkaline phosphatase and ecto-5'-nucleotidase with potential anticancer activity.
AB  - Ecto-nucleotidase members i.e., ecto-5'-nucleotidase and alkaline phosphatase,
      hydrolyze extracellular nucleotides and play an important role in purinergic
      signaling. Their overexpression are implicated in a variety of pathological
      states, including immunological diseases, bone mineralization, vascular
      calcification and cancer, and thus they represent an emerging drug targets. In
      order to design potent and selective inhibitors, new derivatives of 4
      aminopyridine have been synthesized (10a-10m) and their structures were
      established on the basis of spectral data. The effect of nature and position of
      substituent was interestingly observed and justified on the basis of their
      detailed structure activity relationships (SARs) against both families of ecto
      nucleotidase. Compound 10a displayed significant inhibition (IC50 +/- SEM = 0.25
      +/- 0.05 uM) that was found ~168 fold more potent as compared to previously
      reported inhibitor suramin (IC50 +/- SEM = 42.1 +/- 7.8 uM). This compound
      exhibited 6 times more selectivity towards h-TNAP over h-e5'NT. The anticancer
      potential and mechanism were also established using cell viability assay, flow
      cytometric analysis and nuclear staining. Molecular docking studies were also
      carried out to gain insight into the binding interaction of potent compounds
      within the respective enzyme pockets and herring-sperm DNA.

PMID- 29197226
TI  - Tolerance of negative emotion moderates the amplification of mental contamination
      following an evoking task: A randomized experimental study.
AB  - BACKGROUND AND OBJECTIVES: Contamination is a near universal feeling, with mental
      contamination representing a contamination feeling in the absence of direct
      physical contact with a source. Extant research indicates that tolerance of
      negative emotion is important for understanding emotional reactions to images,
      thoughts, and memories, all of which are common sources of mental contamination.
      Extending research linking distress tolerance to mental contamination, this study
      examined if individual differences in the tolerance of negative emotion moderates
      the amplification of mental contamination following an evoking task. METHOD:
      Unselected participants completed a self-report measure of tolerance of negative
      emotion during an online session. They later attended an in-person session and
      were randomized to an experimental scenario group: betrayal (n = 49) or control
      (n = 49). Participants imagined themselves in a scenario, with the betrayal
      scenario designed to evoke mental contamination. Mental contamination was
      assessed by self-report before and after the scenario. RESULTS: The betrayal, but
      not control, scenario caused an increase in mental contamination. Tolerance for
      negative emotion moderated the effect of group on mental contamination. Group
      differences in mental contamination evidenced at low, but not high, distress
      tolerance. LIMITATIONS: A novel experimental manipulation and an unselected
      sample were used. Future research could assess tolerance of negative emotion
      using a behavioral task. CONCLUSIONS: These results indicate that tolerance of
      negative emotion may be important for understanding when individuals experience
      mental contamination.

PMID- 29197227
TI  - Involvement of the middle frontal gyrus in language switching as revealed by
      electrical stimulation mapping and functional magnetic resonance imaging in
      bilingual brain tumor patients.
AB  - Neural basis of language switching and the cognitive models of bilingualism
      remain controversial. We explored the functional neuroanatomy of language
      switching implementing a new multimodal protocol assessing neuropsychological,
      functional magnetic resonance and intraoperative electrical stimulation mapping
      results. A prospective series of 9 Spanish-Catalan bilingual candidates for awake
      brain surgery underwent a specific language switching paradigm implemented both
      before and after surgery, throughout the electrical stimulation procedure and
      during functional magnetic resonance both pre- and postoperatively. All patients
      were harboring left-hemispheric intrinsic brain lesions and were presenting
      functional language-related activations within the affected hemisphere. Language
      functional maps were reconstructed on the basis of the intraoperative electrical
      stimulation results and compared to the functional magnetic resonance findings.
      Single language-naming sites (Spanish and Catalan), as well as language switching
      naming sites were detected by electrical stimulation mapping in 8 patients (in
      one patient only Spanish related sites were detected). Single naming points
      outnumbered the switching points and did not overlap with each other. Within the
      frontal lobe, the single language naming sites were found significantly more
      frequently within the inferior frontal gyrus as compared to the middle frontal
      gyrus [X2 (1) = 20.3, p < .001]. Contrarily, switching naming sites were
      distributed across the middle frontal gyrus significantly more often than within
      the inferior frontal gyrus [X2 (1) = 4.1, p = .043]. Notably, there was not
      always an overlap between functional magnetic resonance and electrical
      stimulation mapping findings. After surgery, patients did not report involuntary
      language switching and their neuropsychological scores did not differ
      significantly from the pre-surgical examinations. Our results suggest a
      functional division of the frontal cortex between naming and language switching
      functions, supporting that non-language specific cognitive control prefrontal
      regions (middle frontal gyrus) are essential to maintain an effective
      communication together with the classical language-related sites (inferior
      frontal gyrus).

PMID- 29197228
TI  - Are carer attitudes toward medications related to self-reported medication
      adherence amongst people with mental illness?
AB  - Medication nonadherence among consumers with psychiatric disorders can
      significantly affect the health and wellbeing of the consumer and their family.
      Previous research has suggested that carers have an impact on consumer attitudes
      toward medication and adherence. Yet, how carer attitudes toward medication may
      be related to consumer attitudes and adherence has received little investigation.
      This exploratory study aimed to investigate the relationships between carer and
      consumer attitudes toward medication and consumer adherence behaviour. A cross
      sectional survey assessing consumer and carer attitudes toward medication and
      consumer adherence was conducted amongst 42 consumer-carer dyads. Correlation
      analyses showed a positive association between consumer and carer attitudes
      toward medication and between consumer and carer attitudes with adherence. There
      was a general indication that the greater the difference between consumer and
      carer attitudes, the lower the level of adherence. Regression analyses revealed
      that while neither consumer nor carer attitudes were significant predictors of
      adherence, carer attitudes appeared to have a stronger role in adherence than
      consumer attitudes. These preliminary results highlight the importance of carer
      attitudes in relation to patient perceptions and behaviours toward medication,
      and thus the potential benefits of addressing both consumer and carer attitudes
      in any intervention for improving adherence.

PMID- 29197229
TI  - Photocatalytic degradation and mineralization of perfluorooctanoic acid (PFOA)
      using a composite TiO2 -rGO catalyst.
AB  - The inherent resistance of perfluoroalkyl substances (PFASs) to biological
      degradation makes necessary to develop advanced technologies for the abatement of
      this group of hazardous substances. The present work investigated the
      photocatalytic decomposition of perfluorooctanoic acid (PFOA) using a composite
      catalyst based on TiO2 and reduced graphene oxide (95% TiO2/5% rGO) that was
      synthesized using a facile hydrothermal method. The efficient photoactivity of
      the TiO2-rGO (0.1gL-1) composite was confirmed for PFOA (0.24mmolL-1) degradation
      that reached 93+/-7% after 12h of UV-vis irradiation using a medium pressure
      mercury lamp, a great improvement compared to the TiO2 photocatalysis (24+/-11%
      PFOA removal) and direct photolysis (58+/-9%). These findings indicate that rGO
      provided the suited properties of TiO2-rGO, possibly as a result of acting as
      electron acceptor and avoiding the high recombination electron/hole pairs. The
      release of fluoride and the formation of shorter-chain perfluorocarboxilyc acids,
      that were progressively eliminated in a good match with the analysed reduction of
      total organic carbon, is consistent with a step-by-step PFOA decomposition via
      photogenerated hydroxyl radicals. Finally, the apparent first order rate
      constants of the TiO2-rGO UV-vis PFOA decompositions, and the intermediate
      perfluorcarboxylic acids were found to increase as the length of the carbon chain
      was shorter.

PMID- 29197230
TI  - The influence of prior reputation and reciprocity on dynamic trust-building in
      adults with and without autism spectrum disorder.
AB  - The present study was designed to investigate the effects of reputational priors
      and direct reciprocity on the dynamics of trust building in adults with (N = 17)
      and without (N = 25) autism spectrum disorder (ASD) using a multi-round Trust
      Game (MTG). On each round, participants, who played as investors, were required
      to maximize their benefits by updating their prior expectations (the partner's
      positive or negative reputation), based on the partner's directed reciprocity,
      and adjusting their own investment decisions accordingly. Results showed that
      reputational priors strongly oriented the initial decision to trust,
      operationalized as the amount of investment the investor shares with the
      counterpart. However, while typically developed participants were mainly affected
      by the direct reciprocity, and rapidly adopted the optimal Tit-for-Tat strategy,
      participants with ASD continued to rely on reputational priors throughout the
      game, even when experience of the counterpart's actual behavior contradicted
      their prior-based expectations. In participants with ASD, the effect of the
      reputational prior never disappeared, and affected judgments of trustworthiness
      and reciprocity of the partner even after completion of the game. Moreover, the
      weight of prior reputation positively correlated with the severity of the ASD
      participant's social impairments while the reciprocity score negatively
      correlated with the severity of repetitive and stereotyped behaviors, as measured
      by the Autism Diagnostic Interview-Revised (ADI-R). In line with Bayesian
      theoretical accounts, the present findings indicate that individuals with ASD
      have difficulties encoding incoming social information and using it to revise and
      flexibly update prior social expectations, and that this deficit might severely
      hinder social learning and everyday life interactions.

PMID- 29197231
TI  - Uptake and effects of 2, 4, 6 - trinitrotoluene (TNT) in juvenile Atlantic salmon
      (Salmo salar).
AB  - Organ specific uptake and depuration, and biological effects in Atlantic salmon
      (Salmo salar) exposed to 2, 4, 6-trinitrotoluene (TNT) were studied. Two
      experiments were conducted, the first using radiolabeled TNT (14C-TNT, 0.16mg/L)
      to study uptake (48h) and depuration (48h), while the second experiment focused
      on physiological effects in fish exposed to increasing concentrations of
      unlabeled TNT (1MUg-1mg/L) for 48h. The uptake of 14C-TNT in the gills and most
      of the organs increased rapidly during the first 6h of exposure (12h in the
      brain) followed by a rapid decrease even though the fish were still exposed to
      TNT in the water. The radioactivity in the gall bladder reached a maximum after
      55h, 7h after the transfer to the clean water. A high concentration of 14C-TNT in
      the gall bladder indicates that TNT is excreted through the gall bladder.
      Mortality (2 out of 14) was observed at a concentration of 1mg/L, and the
      surviving fish had hemorrhages in the dorsal muscle tissue near the spine.
      Analysis of the physiological parameters in blood from the high exposure group
      revealed severe effects, with an increase in the levels of glucose, urea and
      HCO3, and a decrease in hematocrit and the levels of Cl and hemoglobin. No
      effects on blood physiology were observed in fish exposed to the lower
      concentrations of TNT (1-100MUg/L). TNT and the metabolites 2-amino-4,6
      dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT) were found in the
      muscle tissue, whereas only 2-ADNT and 4-ADNT were found in the bile. The rapid
      excretion and estimated bioconcentration factors (range of 2-18 after 48h in
      gills, blood, liver, kidney, muscle and brain) indicated a low potential for
      bioaccumulation of TNT.

PMID- 29197232
TI  - Uptake, tissue distribution, and toxicity of polystyrene nanoparticles in
      developing zebrafish (Danio rerio).
AB  - Plastic pollution is a critical environmental concern and comprises the majority
      of anthropogenic debris in the ocean, including macro, micro, and likely
      nanoscale (less than 100nm in at least one dimension) plastic particles. While
      the toxicity of macroplastics and microplastics is relatively well studied, the
      toxicity of nanoplastics is largely uncharacterized. Here, fluorescent
      polystyrene nanoparticles (PS NPs) were used to investigate the potential
      toxicity of nanoplastics in developing zebrafish (Danio rerio), as well as to
      characterize the uptake and distribution of the particles within embryos and
      larvae. Zebrafish embryos at 6h post-fertilization (hpf) were exposed to PS NPs
      (0.1, 1, or 10ppm) until 120 hpf. Our results demonstrate that PS NPs accumulated
      in the yolk sac as early as 24 hpf and migrated to the gastrointestinal tract,
      gallbladder, liver, pancreas, heart, and brain throughout development (48-120
      hpf). Accumulation of PS NPs decreased during the depuration phase (120-168 hpf)
      in all organs, but at a slower rate in the pancreas and gastrointestinal tract.
      Notably, exposure to PS NPs did not induce significant mortality, deformities, or
      changes to mitochondrial bioenergetics, but did decrease the heart rate. Lastly,
      exposure to PS NPs altered larval behavior as evidenced by swimming hypoactivity
      in exposed larvae. Taken together, these data suggest that at least some
      nanoplastics can penetrate the chorion of developing zebrafish, accumulate in the
      tissues, and affect physiology and behavior, potentially affecting organismal
      fitness in contaminated aquatic ecosystems.

PMID- 29197234
TI  - Identifying risk factors for first-episode neck pain: A systematic review.
AB  - Neck pain affects 15.1% of the United States' general population every 3 months,
      and ranks fourth in global disability. Because of the tendency for neck pain to
      become a chronic issue, it is important to identify risk factors that could
      encourage prevention and early diagnosis. The purpose of this systematic review
      was to identify risk factors for a first episode of neck pain. Three databases
      were searched with key words such as "neck pain" and "first incidence." Risk
      factors from the resulting articles were reported as either a physical or
      psychosocial risk factor and ranked by the strength of their odds/risk/hazard
      ratio: <1.0 (protective factor), 1.0-1.5 (minor risk), 1.5-2.0 (moderate risk),
      or 2.0+ (major risk). Out of 878 total articles, 10 articles met our inclusion
      criteria. Of these studies, a global incidence rate for neck pain was calculated
      to be 16.2%. The strongest psychosocial risk factors were depressed mood, high
      role conflict, and perceived muscular tension. There were no major physical risk
      factors (2.0+), but the most commonly reported risk factor was work in
      awkward/sustained postures. Protective measures found included high perceived
      empowering leadership, high perceived social climate, leisure physical activity,
      and cervical extensor endurance. Most risk factors found for neck pain were
      related to psychosocial characteristics, rather than physical characteristics. A
      number of these risk factors were mediating factors, suggesting that a prevention
      based program may be useful in modifying the existence of the risk factors before
      the occurrence of neck pain.

PMID- 29197233
TI  - Cholinergic anti-inflammatory pathway inhibits neointimal hyperplasia by
      suppressing inflammation and oxidative stress.
AB  - Neointimal hyperplasia as a consequence of vascular injury is aggravated by
      inflammatory reaction and oxidative stress. The alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR) is a orchestrator of cholinergic anti-inflammatory pathway
      (CAP), which refers to a physiological neuro-immune mechanism that restricts
      inflammation. Here, we investigated the potential role of CAP in neointimal
      hyperplasia using alpha7nAChR knockout (KO) mice. Male alpha7nAChR-KO mice and
      their wild-type control mice (WT) were subjected to wire injury in left common
      carotid artery. At 4 weeks post injury, the injured aortae were isolated for
      examination. The neointimal hyperplasia after wire injury was significantly
      aggravated in alpha7nAChR-KO mice compared with WT mice. The alpha7nAChR-KO mice
      had increased collagen contents and vascular smooth muscle cells (VSMCs) amount.
      Moreover, the inflammation was significantly enhanced in the neointima of
      alpha7nAChR-KO mice relative to WT mice, evidenced by the increased expression of
      tumor necrosis factor-alpha/interleukin-1beta, and macrophage infiltration.
      Meanwhile, the chemokines chemokine (C-C motif) ligand 2 and chemokine (CXC
      motif) ligand 2 expression was also augmented in the neointima of alpha7nAChR-KO
      mice compared with WT mice. Additionally, the depletion of superoxide dismutase
      (SOD) and reduced glutathione (GSH), and the upregulation of 3-nitrotyrosine,
      malondialdehyde and myeloperoxidase were more pronounced in neointima of
      alpha7nAChR-KO mice compared with WT mice. Accordingly, the protein expression of
      NADPH oxidase 1 (Nox1), Nox2 and Nox4, was also higher in neointima of
      alpha7nAChR-KO mice compared with WT mice. Finally, pharmacologically activation
      of CAP with a selective alpha7nAChR agonist PNU-282987, significantly reduced
      neointima formation, arterial inflammation and oxidative stress after vascular
      injury in C57BL/6 mice. In conclusion, our results demonstrate that alpha7nAChR
      mediated CAP is a neuro-physiological mechanism that inhibits neointima formation
      after vascular injury via suppressing arterial inflammation and oxidative stress.
      Further, these results imply that targeting alpha7nAChR may be a promising
      interventional strategy for in-stent stenosis.

PMID- 29197235
TI  - The relationship of school climate, teacher defending and friends on students'
      perceptions of bullying in high school.
AB  - The purpose of this study was to examine the relationship of school climate,
      teacher defending, and friends on bullying and victimization. Participants were
      2273 high school students from 3 public schools (an all girls, all boys boarding,
      and a co-ed day) in Kenya. A structural equation model was used to examine
      relationships between school climate, teacher behavior toward bullying, and
      student demographic characteristics, and bullying. Results revealed that a
      positive school climate was associated with less bullying behavior and
      victimization. In addition, when students reported that teachers stop bullying by
      students, bullying behavior and victimization scores were lower. Contrary to
      previous research these results showed that residents of a boys only boarding
      school were less likely to report bullying behavior than residents of an all
      girls school, or students at a co-educational institution. Furthermore, there
      were no differences in bullying behavior or victimization by gender or grade
      level. Implications of these results are discussed.

PMID- 29197236
TI  - The roles of parenting practices, sociocognitive/emotive traits, and prosocial
      behaviors in low-income adolescents.
AB  - The goal of the current study was to examine the links among parenting practices
      (i.e., use of social and material rewards), sociocognitive and socioemotive
      traits (i.e., perspective taking, prosocial moral reasoning, and empathic
      concern), and prosocial behaviors among adolescents in a low-income, Midwestern
      community. Participants were 311 adolescents (M age = 16.10 years; range = 14-19
      years; 58.7% girls; 82.7% White; 13.6% Latino). The results demonstrated that
      social rewards were positively associated with perspective taking, empathic
      concern, and prosocial moral reasoning, which were each associated with multiple
      forms of prosocial behaviors. Material rewards were negatively associated with
      prosocial moral reasoning and empathic concern. There were also direct links
      between material and social rewards and prosocial behaviors. Discussion will
      focus on the intervening role of social cognitions and emotions in explaining
      links between parenting practices and low-income adolescents' prosocial
      behaviors.

PMID- 29197237
TI  - The rise in obesity in Cuba from 2001 to 2010: An analysis of National Survey on
      Risk Factors and Chronic Diseases data.
AB  - Using two waves of the National Survey on Risk Factors and Chronic Diseases in
      Cuba, we identify demographic and socioeconomic characteristics associated with
      obesity among urban adults aged 18+ and decompose the change in obesity within
      this 9-year period using both the mean-based Blinder-Oaxaca decomposition and a
      nonlinear approach. Our results reveal significant increases in overweight and
      obesity (2.3, 3.1, and 7.6 percentage points for BMI-based overweight, BMI-based
      obesity, and abdominal obesity, respectively). Depending on the decompositional
      approach and obesity measure, our analysis explains between 13% and 51% of the
      rise in overweight and obesity, with most part attributable to changes in risky
      behavior, age, and education. Of particular importance are the large decline in
      smoking and the population's changing age structure.

PMID- 29197238
TI  - Food insecurity and child behavior problems in fragile families.
AB  - Food insecurity remains a persistent problem in the United States. Several
      studies have shown that food insecurity is associated with child externalizing
      and internalizing behavior problems. However, some potential methodological
      limitations remain. For example, most studies use a household measure of food
      insecurity while there is evidence that children, especially younger ones, tend
      to be shielded by their parents from experiencing food insecurity. In addition,
      the mechanisms through which food insecurity affects children are not well
      understood. This study uses longitudinal data from the Fragile Families and Child
      Wellbeing Study to address these limitations. Fixed-effects models show that the
      association is even larger using a measure of child food insecurity instead of a
      household one. Correlated-random effects models show a large difference in child
      behavior problems between food secure and food insecure children due to
      unobserved heterogeneity. In addition, the association between child food
      insecurity and child externalizing behaviors remains largely unexplained while
      food insecurity among adults explains almost all the variation in the association
      with child internalizing behaviors. Food insecure children and parents are at
      risk of micronutrient deficiencies, which may lead to behavior problems in young
      children. These findings underscore the need for greater focus on reducing the
      risk of food insecurity, especially for children in fragile families, in order to
      reduce behavior problems and improve their educational attainment.

PMID- 29197239
TI  - Age at menarche in Polish University students born before, during and after World
      War II: Economic effects.
AB  - Although the relationships between economic conditions and biological variables
      over the past two centuries in Poland are reasonably well-documented, the
      influence of economic and political disruptions, including nutritional privation,
      during the years immediately before, during and shortly after World War II (WWII)
      has received less attention. This paper considers the association between age at
      menarche and body size of university students born before, during and after WWII
      and father's level of education, a commonly used indicator of family economic
      status in Poland. Subjects were 518 university students surveyed between 1955 and
      1972, birth years 1931 through 1951. The sample was divided into three birth
      cohorts: before (n=237), during (n=247) and after (n=34) WWII. Age at menarche
      was compared among birth cohorts, and by weight status and father's level of
      education. Age at menarche increased slightly but significantly among women born
      during WWII (14.4 yrs) compared to those born before (14.2 yrs) and after (13.9
      yrs) the war. Controlling for year of birth and age of the student, age at
      menarche was significantly earlier in overweight (13.42+/-0.35 yrs) than in
      normal weight (14.33+/-0.06 yrs) and thin (14.54+/-0.21 yrs) women. Adjusted mean
      ages at menarche in small samples of overweight women did not differ by father's
      level of education, and were earlier than corresponding ages of thin and normal
      weight women. Adjusted mean ages at menarche did not differ between thin and
      normal weight women with fathers having primary or no education, but were
      slightly later in thin than in normal weight women with fathers having a
      vocational, secondary or higher education. Although age at menarche was
      associated with father's level of education, young adult weight status was a
      somewhat more important correlate.

PMID- 29197240
TI  - Macroeconomic conditions and health: Inspecting the transmission mechanism.
AB  - We study the relationship between macroeconomic conditions and self-reported
      health in a large sample of Italian individuals, focusing on the mediating role
      played by health behaviors (smoking, alcohol consumption, physical activity,
      eating habits) and economic stress. Our findings indicate that, overall, higher
      local unemployment is negatively related to individuals' health conditions. A one
      percentage point increase in the province-level unemployment rate is associated
      with a significant increase in the probability of experiencing diabetes (0.03
      percentage points), infarction (0.01), ulcer (0.06), cirrhosis (0.01) and nervous
      disorders (0.07), with a time lag that differs across individual health
      conditions. Employment status and educational level play a significant role as
      moderators of these relationships. Eating habits, in addition to economic stress,
      play a key role as mediators, by enhancing the negative relationship between
      macroeconomic conditions and health outcomes, while physical exercise is found to
      play a dampening role.

PMID- 29197241
TI  - Iconicity affects children's comprehension of complex sentences: The role of
      semantics, clause order, input and individual differences.
AB  - Complex sentences involving adverbial clauses appear in children's speech at
      about three years of age yet children have difficulty comprehending these
      sentences well into the school years. To date, the reasons for these difficulties
      are unclear, largely because previous studies have tended to focus on only sub
      types of adverbial clauses, or have tested only limited theoretical models. In
      this paper, we provide the most comprehensive experimental study to date. We
      tested four-year-olds, five-year-olds and adults on four different adverbial
      clauses (before, after, because, if) to evaluate four different theoretical
      models (semantic, syntactic, frequency-based and capacity-constrained). 71
      children and 10 adults (as controls) completed a forced-choice, picture-selection
      comprehension test, providing accuracy and response time data. Children also
      completed a battery of tests to assess their linguistic and general cognitive
      abilities. We found that children's comprehension was strongly influenced by
      semantic factors - the iconicity of the event-to-language mappings - and that
      their response times were influenced by the type of relation expressed by the
      connective (temporal vs. causal). Neither input frequency (frequency-based
      account), nor clause order (syntax account) or working memory (capacity
      constrained account) provided a good fit to the data. Our findings thus
      contribute to the development of more sophisticated models of sentence
      processing. We conclude that such models must also take into account how
      children's emerging linguistic understanding interacts with developments in other
      cognitive domains such as their ability to construct mental models and reason
      flexibly about them.

PMID- 29197242
TI  - Alcohol and illicit drugs in drivers involved in road traffic crashes in the
      Milan area. A comparison with normal traffic reveals the possible inadequacy of
      current cut-off limits.
AB  - BACKGROUND: Driving under the influence of alcohol and/or illicit drugs in Italy
      is regulated by the articles 186 and 187 of the National Street Code.
      Epidemiological studies on drivers involved in road traffic crashes (RTC) provide
      useful information about the use/abuse of these substances in the general
      population. Comparison with case control studies may reveal important information
      like the cut-off limits adequacy. METHODS: Data from 1587 blood tests for alcohol
      and 1258 blood tests for illicit drugs on drivers involved in RTC around Milan
      between 2012 and 2016, were analyzed and compared with a published random survey
      (DRUID) from the European Community. RESULTS: Our data from RTC-involved drivers
      show that alcohol abuse is not age-related whereas illicit drugs are more common
      in young people. Cannabinoids are frequent among younger drivers (median age 27)
      whereas cocaine is more often detected in adults (median age 34). The calculated
      odds ratio after comparison with the DRUID survey shows that a blood alcohol
      concentration below the legal limit does not represent a risk factor in having a
      car accident whereas concentrations of cocaine and cannabinoids within the legal
      limits are associated with being involved in a car accident. CONCLUSIONS: Despite
      authority efforts, the abuse of alcohol and illicit drugs is still common in
      young drivers. We suspect that the cut-off limits for cannabinoids and cocaine
      and/or the pre-analytical procedures for these substances are inadequate. We
      suggest a better standardization of the procedure by shortening the time interval
      between the request for investigation and blood collection and propose the
      adoption of more stringent cut-off limits.

PMID- 29197243
TI  - Automated facial recognition of manually generated clay facial approximations:
      Potential application in unidentified persons data repositories.
AB  - This research examined how accurately 2D images (i.e., photographs) of 3D clay
      facial approximations were matched to corresponding photographs of the
      approximated individuals using an objective automated facial recognition system.
      Irrespective of search filter (i.e., blind, sex, or ancestry) or rank class (R1,
      R10, R25, and R50) employed, few operationally informative results were observed.
      In only a single instance of 48 potential match opportunities was a clay
      approximation matched to a corresponding life photograph within the top 50 images
      (R50) of a candidate list, even with relatively small gallery sizes created from
      the application of search filters (e.g., sex or ancestry search restrictions).
      Increasing the candidate lists to include the top 100 images (R100) resulted in
      only two additional instances of correct match. Although other untested variables
      (e.g., approximation method, 2D photographic process, and practitioner skill
      level) may have impacted the observed results, this study suggests that 2D images
      of manually generated clay approximations are not readily matched to life photos
      by automated facial recognition systems. Further investigation is necessary in
      order to identify the underlying cause(s), if any, of the poor recognition
      results observed in this study (e.g., potential inferior facial feature detection
      and extraction). Additional inquiry exploring prospective remedial measures
      (e.g., stronger feature differentiation) is also warranted, particularly given
      the prominent use of clay approximations in unidentified persons casework.

PMID- 29197244
TI  - Systematic assessment of different solvents for the extraction of drugs of abuse
      and pharmaceuticals from an authentic hair pool.
AB  - Hair analysis has been established as a prevalent tool for retrospective drug
      monitoring. In this study, different extraction solvents for the determination of
      drugs of abuse and pharmaceuticals in hair were evaluated for their efficiency. A
      pool of authentic hair from drug users was used for extraction experiments. Hair
      was pulverized and extracted in triplicate with seven different solvents in a one
      or two-step extraction. Three one- (methanol, acetonitrile, and
      acetonitrile/water) and four two-step extractions (methanol two-fold, methanol
      and methanol/acetonitrile/formate buffer, methanol and methanol/formate buffer,
      and methanol and methanol/hydrochloric acid) were tested under accurately equal
      experimental conditions. The extracts were directly analyzed by liquid
      chromatography-tandem mass spectrometry for opiates/opioids, stimulants,
      ketamine, selected benzodiazepines, antidepressants, antipsychotics, and
      antihistamines using deuterated internal standards. For most analytes, a two-step
      extraction with methanol did not significantly improve the yield compared to a
      one-step extraction with methanol. Extraction with acetonitrile alone was least
      efficient for most analytes. Extraction yields of acetonitrile/water, methanol
      and methanol/acetonitrile/formate buffer, and methanol and methanol/formate
      buffer were significantly higher compared to methanol. Highest efficiencies were
      obtained by a two-step extraction with methanol and methanol/hydrochloric acid,
      particularly for morphine, 6-monoacetylmorphine, codeine, 6-acetylcodeine, MDMA,
      zopiclone, zolpidem, amitriptyline, nortriptyline, citalopram, and doxylamine.
      For some analytes (e.g., tramadol, fluoxetine, sertraline), all extraction
      solvents, except for acetonitrile, were comparably efficient. There was no
      significant correlation between extraction efficiency with an acidic solvent and
      the pka or log P of the analyte. However, there was a significant trend for the
      extraction efficiency with acetonitrile to the log P of the analyte. The study
      demonstrates that the choice of extraction solvent has a strong impact on hair
      analysis outcomes. Therefore, validation protocols should include the evaluation
      of extraction efficiency of drugs by using authentic rather than spiked hair.
      Different extraction procedures may contribute to the scatter of quantitative
      results in inter-laboratory comparisons. Harmonization of extraction protocols is
      recommended, when interpretation is based on same cut-off levels.

PMID- 29197245
TI  - The geographic mosaic of Ecuadorian Y-chromosome ancestry.
AB  - Ecuadorians originated from a complex mixture of Native American indigenous
      people with Europeans and Africans. We analyzed Y-chromosome STRs (Y-STRs) in a
      sample of 415 Ecuadorians (145 using the AmpFlSTR(r) YfilerTM system [Life
      Technologies, USA] and 270 using the PowerPlex(r)Y23 system [Promega Corp., USA];
      hereafter Yfiler and PPY23, respectively) representing three main ecological
      continental regions of the country, namely Amazon rainforest, Andes, and Pacific
      coast. Diversity values are high in the three regions, and the PPY23 exhibits
      higher discrimination power than the Yfiler set. While summary statistics, AMOVA,
      and RST distances show low to moderate levels of population stratification,
      inferred ancestry derived from Y-STRs reveal clear patterns of geographic
      variation. The major ancestry in Ecuadorian males is European (61%), followed by
      an important Native American component (34%); whereas the African ancestry (5%)
      is mainly concentrated in the Northwest corner of the country. We conclude that
      classical procedures for measuring population stratification do not have the
      desirable sensitivity. Statistical inference of ancestry from Y-STRS is a
      satisfactory alternative for revealing patterns of spatial variation that would
      pass unnoticed when using popular statistical summary indices.

PMID- 29197246
TI  - Combined toxicity of endosulfan and phenanthrene mixtures and induced molecular
      changes in adult Zebrafish (Danio rerio).
AB  - Individual and combined toxicities of endosulfan (ENDO) with phenanthrene (PHE)
      were evaluated using zebrafish (Danio rerio) adults. The 96-h LC50 values for
      ENDO and PHE were 4.6 MUg L-1 and 920 MUg L-1, respectively. To evaluate the
      mixture toxicity, LC10 and LC50 concentrations were grouped into four
      combinations as ENDO-LC10 + PHE-LC10, ENDO-LC10 + PHE-LC50, ENDO-LC50 + PHE-LC10,
      and ENDO-LC50 + PHE-LC50, and their acute toxicities were determined. The
      combination of LC50-ENDO and LC10-PHE exhibited a synergistic effect. In
      addition, acetylcholinesterase activity decreased in zebrafish bodies exposed to
      ENDO with or without PHE. Combined treatments induced higher glutathione S
      transferase activity compared to individual treatments. Carboxylesterase activity
      increased in both heads and bodies of ENDO-treated fishes compared with PHE
      treated fishes. Using RT-qPCR technique, CYP1A gene expression significantly up
      regulated in all combinations, whereas CYP3A was unchanged, suggesting that
      enzymes involved in defense may play different roles in the detoxification.
      CYP7A1 gene responsible for bile acid biosynthesis is dramatically down-regulated
      after exposure to the synergistic combination exposure, referring that the
      synergistic effect may be resulted from the reduction of bile production in
      zebrafishes. Among gender-related genes, CYP11A1 and CYP17A1 genes in female
      zebrafish decreased after treatment with ENDO alone and combination of LC50-ENDO
      and LC10-PHE. This might be related to a reduction in cortisol production. The
      overall results indicated that ENDO and PHE were toxic to zebrafish adults both
      individually and in combination, and that their co-presence induced changes in
      the expression of genes responsible for metabolic processes and defense
      mechanisms.

PMID- 29197247
TI  - Comment on "Changes in activation energy and kinetics of heat-activated
      persulfate oxidation of phenol in response to changes in pH and temperature".

PMID- 29197248
TI  - The role of IL-8/CXCR2 signaling in microcystin-LR triggered endothelial cell
      activation and increased vascular permeability.
AB  - Microcystins are a family of cyclic heptapeptide toxins naturally produced by
      freshwater cyanobacteria. Microcystin-LR (MCLR) is believed to be the most toxic
      and common one with various pathological effects on human and mammals. However,
      the effects of MCLR on endothelial cells and vascular homeostasis have been
      largely unknown. We explored the mRNA and protein expression changes of several
      pro-inflammatory mediators in human umbilical vein endothelial cells (HUVECs) and
      C57BC/6 mice exposed to MCLR. Tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), especially interleukin-8 (IL
      8) were remarkably upregulated both in endothelial cells and in serum. Increased
      endothelial permeability in vitro and chronic microvascular permeability in
      animals were also observed. Silencing the IL-8 gene with siRNA or blocking its
      cognate receptor, CXC-chemokine receptor type 2 (CXCR2), by a specific inhibitor
      efficiently prevented the MCLR induced leakage. These observations indicate a
      novel insight of inflammation triggered property of MCLR via IL-8/CXCR2
      signaling, suggesting CXCR2 as a target molecule in protective strategy against
      the wide range pollution of microcystin.

PMID- 29197249
TI  - Characterising microbial reduction of arsenate sorbed to ferrihydrite and its
      concurrence with iron reduction.
AB  - A series of model anoxic incubations were performed to understand the concurrence
      between arsenate and ferrihydrite reduction by Shewanella putrefaciens strain CN
      32 at different concentrations of arsenate, ferrihydrite and lactate, and with
      given DeltaGrxn for arsenate and ferrihydrite reduction in non-growth conditions.
      The reduction kinetics of arsenate sorbed to ferrihydrite is predominately
      controlled by the availability of dissolved arsenate, which is measured by the
      integral of dissolved arsenate concentrations against incubation time and shown
      to correlate with the first order rate constants. High lactate concentrations
      slightly slowed down the rate of arsenate reduction due to the competition with
      arsenate for microbial contact. Under all experimental conditions, simultaneous
      arsenate and ferrihydrite reduction occurred following addition of S.
      putrefaciens inoculums and suggested no apparent competition between these two
      enzymatic reductions. Ferrous ions released from iron reduction might retard
      microbial arsenate reduction at high arsenate and ferrihydrite concentrations due
      to formation of ferrous arsenate. At high arsenate to ferrihydrite ratios,
      reductive dissolution of ferrihydrite shifted arsenate from sorption to
      dissolution and hence accelerated arsenate reduction. The interaction between
      microbial arsenate and ferrihydrite reduction did not correlate with DeltaGrxn,
      but instead was governed by other factors such as geochemical and microbial
      parameters.

PMID- 29197250
TI  - In utero single low-dose exposure of cadmium induces rat fetal Leydig cell
      dysfunction.
AB  - Cadmium chloride (Cd) is a potent endocrine disruptor and may cause the
      malformation in the male reproductive tract. However, the effects of a single in
      utero exposure to low doses of Cd on fetal Leydig cell development are still
      unknown. The objective of this study is to investigate the effects of a single in
      utero exposure to low doses of Cd on rat fetal Leydig cell development. Adult 64
      day-old Sprague-Dawley dams received a single intraperitoneal injection of 0,
      0.25, 0.5, and 1.0 mg/kg Cd on gestational day 12. Cd dose-dependently reduced
      testosterone production of fetal testis, lowered fetal Leydig cell numbers,
      downregulated protein expression levels of Leydig (LHCGR, SCARB1, STAR, CYP11A1,
      HSD3B1, and CYP17A1), and Sertoli cells (HSD17B3, DHH, and FSHR). In conclusion,
      our results demonstrated that a single in utero exposure to low doses of Cd
      blocked fetal Leydig cell development.

PMID- 29197251
TI  - "The next-generation": Long-term reproductive outcome of adults born at a very
      low birth weight.
AB  - BACKGROUND: Preterm birth at very low birth weight (VLBW, <1500g) has a multitude
      of consequences that extend to various aspects of adult life. Little is known
      about the long-term reproductive outcome of VLBW that survive to adulthood. AIMS:
      To evaluate the reproductive outcome of VLBW infants who survive to adulthood
      (next-generation). STUDY DESIGN: Retrospective cohort. SUBJECTS: Infants born at
      a single tertiary center between the years 1982-1997 who survived to 18years of
      age (first-generation). OUTCOME MEASURES: The number and the birth weight of
      offspring from adults born with VLBW were compared to those of other birth weight
      groups born in the same epoch: 1500-2499g, 2500-3799g (reference group) and
      >=3800g. We calculated the ratio of actual compared to expected number of
      children in the next-generation for extreme birth weight parents, using the
      reference group as a control group and adjusting for birth year. Thereafter, we
      measured whether first-generation VLBW had an increased risk for a VLBW in the
      next-generation. RESULTS: After exclusions, we identified first-generation 67,183
      births, including 618 (9.2%) VLBW. There were 193 males and 184 female VLBW
      infants who survived to adulthood. Both female and male first-generation patients
      from the VLBW group had half the reproductive rate relative for the normal birth
      weight group. After adjusting for parental age, male and female VLBW survivors
      had no significant risk for a VLBW neonate in the next-generation, however, the
      overall number of are small and may limit any conclusion. CONCLUSION: VLBW
      children who reach adulthood may be at a significantly lower reproductive
      capacity.

PMID- 29197252
TI  - Oregano dietary supplementation modifies the liver transcriptome profile in
      broilers: RNASeq analysis.
AB  - Intensive farming of broilers involves stressful conditions that reduce animal
      welfare and performance. New dietary strategies to improve performance and meat
      quality include the administration of plant extracts. Oregano (Origanum vulgare
      L.) is known for its antimicrobial, anti-fungal, insecticidal and antioxidant
      properties. However, studies on diet supplementation with oregano are mainly
      focused on the evaluation of animal performance, while partial information is
      available on transcriptomics and nutrigenomics and, in particular, Next
      Generation Sequencing (NGS) is not widely applied. In this study we tested the
      effect of an oregano aqueous extract supplemented diet on gene expression in
      broiler chickens. Whole liver transcriptome of 10 birds fed with a supplemented
      diet versus 10 controls was analyzed using the RNA-Seq technique. One hundred and
      twenty-nine genes were differentially expressed with an absolute log fold change
      >1. The analysis reveals a massive down-regulation of genes involved in fatty
      acid metabolism and insulin signaling pathways in broilers fed with the oregano
      aqueous extract supplementation. Down-regulated genes could be associated to
      chicken lean line, suggesting the potential beneficial effect of oregano
      supplementation in reducing both abdominal and visceral fat deposition. Down
      regulation of insulin signaling pathway related genes suggest that dietary
      oregano supplementation might be an option in obesity and diabetes conditions.

PMID- 29197253
TI  - Deep learning analysis of the myocardium in coronary CT angiography for
      identification of patients with functionally significant coronary artery
      stenosis.
AB  - In patients with coronary artery stenoses of intermediate severity, the
      functional significance needs to be determined. Fractional flow reserve (FFR)
      measurement, performed during invasive coronary angiography (ICA), is most often
      used in clinical practice. To reduce the number of ICA procedures, we present a
      method for automatic identification of patients with functionally significant
      coronary artery stenoses, employing deep learning analysis of the left ventricle
      (LV) myocardium in rest coronary CT angiography (CCTA). The study includes
      consecutively acquired CCTA scans of 166 patients who underwent invasive FFR
      measurements. To identify patients with a functionally significant coronary
      artery stenosis, analysis is performed in several stages. First, the LV
      myocardium is segmented using a multiscale convolutional neural network (CNN). To
      characterize the segmented LV myocardium, it is subsequently encoded using
      unsupervised convolutional autoencoder (CAE). As ischemic changes are expected to
      appear locally, the LV myocardium is divided into a number of spatially connected
      clusters, and statistics of the encodings are computed as features. Thereafter,
      patients are classified according to the presence of functionally significant
      stenosis using an SVM classifier based on the extracted features. Quantitative
      evaluation of LV myocardium segmentation in 20 images resulted in an average Dice
      coefficient of 0.91 and an average mean absolute distance between the segmented
      and reference LV boundaries of 0.7 mm. Twenty CCTA images were used to train the
      LV myocardium encoder. Classification of patients was evaluated in the remaining
      126 CCTA scans in 50 10-fold cross-validation experiments and resulted in an area
      under the receiver operating characteristic curve of 0.74 +/- 0.02. At
      sensitivity levels 0.60, 0.70 and 0.80, the corresponding specificity was 0.77,
      0.71 and 0.59, respectively. The results demonstrate that automatic analysis of
      the LV myocardium in a single CCTA scan acquired at rest, without assessment of
      the anatomy of the coronary arteries, can be used to identify patients with
      functionally significant coronary artery stenosis. This might reduce the number
      of patients undergoing unnecessary invasive FFR measurements.

PMID- 29197254
TI  - Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol
      goal attainment in patients at high and very-high cardiovascular risk: Real-world
      evidence from Germany.
AB  - BACKGROUND AND AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a
      causal risk factor for cardiovascular (CV) events. European guidelines recommend
      reducing LDL-C as the primary lipid target to reduce CV risk, using lifestyle
      modifications and lipid-lowering therapy (LLT). Many European patients do not
      achieve guideline-recommended LDL-C levels. The present database analysis aimed
      to assess LLT treatment patterns and LDL-C threshold attainment in Germany in a
      large, real-world cohort of patients. METHODS: Patients from the Cegedim
      Longitudinal Practice Database in Germany who met selection criteria were
      included: (a) LDL-C measurement in 2013; (b) >=20 years of age; (c) high or very
      high CV risk conditions: recent acute coronary syndrome (ACS), other coronary
      heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD)
      (atherosclerotic cardiovascular disease [ASCVD]) or diabetes mellitus (DM) (non
      ASCVD). LDL-C threshold attainment was assessed based on LDL-C targets from 2011
      European guidelines. RESULTS: 42,767 patients met the inclusion criteria; 35%
      received current statin treatment, and 30% achieved guideline-recommended LDL-C
      targets. Attainment of LDL-C goals among ASCVD hierarchical categories was 46.7%
      for recent ACS, 35.8% for ischemic stroke, 34.9% for other CHD, and 26.9% for
      PAD. Among patients in the non-ASCVD group with DM, 23.6% achieved LDL-C goals.
      Similar results were observed when patients were grouped by prevalence (patients
      assigned to every risk group for which they qualified). CONCLUSIONS: In this
      high/very-high CV risk population in Germany, statin utilization was low;
      suggesting that LLTs are not prescribed as per European guidelines. These results
      highlight the need to increase LLT use among high-risk patients.

PMID- 29197255
TI  - Methane to bioproducts: the future of the bioeconomy?
AB  - Methanotrophs have been studied since the 1970s, but interest has increased
      tremendously in recent years due to their potential to transform methane into
      valuable bioproducts. The vast quantity of available methane and the low price of
      methane as natural gas have helped to spur this interest. The most well-studied,
      biologically-derived products from methane include methanol,
      polyhydroxyalkanoates, and single cell protein. However, many other high-interest
      chemicals such as biofuels or high-value products such as ectoine could be made
      industrially relevant through metabolic engineering. Although challenges must be
      overcome to achieve commercialization of biologically manufactured methane-to
      products, taking a holistic view of the production process or radically re
      imagining pathways could lead to a future bioeconomy with methane as the primary
      feedstock.

PMID- 29197256
TI  - Determination of the formal redox potentials of the
      cyanhaemoglobin/cyanmethaemoglobin and the myoglobin/metmyoglobin couples at
      neutral pH.
AB  - Determination of a representative formal redox potential of the Fe(II)/Fe(III)
      redox couple in cyanhaemoglobin, at pH=7 and related to the state in solution,
      was the objective of this work. It was achieved at low concentrations of the
      protein (5MUM) to circumvent undesired adsorption. Square-wave voltammetry
      instead of classical cyclic voltammetry was applied because this method is more
      sensitive and provides information on the formal redox potential and
      reversibility, even for rapid processes. We obtained E degrees '=-0.12+/-0.01V
      for cyanhaemoglobin and E degrees '=-0.10+/-0.01V, vs. SHE, for myoglobin in
      comparison. These values differ by only 20mV because the two Fe(II)/Fe(III) redox
      centres are embedded in closely resembling chemical environments. The small
      difference is probably owed to the additional axially coordinating cyanide ligand
      in cyanmethaemoglobin which slightly favours the Fe(III) state in the haem
      macrocycle.

PMID- 29197257
TI  - Adsorption/desorption of biomacromolecules involved in catalytic hydrogen
      evolution.
AB  - Previously, it has been shown that proteins and some polysaccharides (PSs)
      catalyse hydrogen evolution, producing electrochemical signals on mercury
      electrodes. The catalytic hydrogen evolution reaction (CHER) of the above
      mentioned biomacromolecules was studied by voltammetric and chronopotentiometric
      stripping (CPS) methods. To obtain more information about electrode processes
      involving CHER, here we used protein such as BSA, and chitosan as a PS; in
      addition, we investigated dextran as a control PS not involved in CHER. We
      studied biomacromolecules by phase-sensitive alternating current (AC)
      voltammetry. Using phase-in AC voltammetry, for CHER-involved biomacromolecules
      we observed a CHER peak at highly negative potentials, similar to that observed
      with other voltammetric and CPS methods. On the other hand, by means of the
      adsorption/desorption processes studied in phase-out AC voltammetry, we uncovered
      a sharp and narrow decrease of capacitive current in the potential range of the
      CHER peak, denominated as the tensammetric minimum. This minimum was closely
      related to the CHER peak, as demonstrated by similar dependences on specific
      conditions affecting the CHER peak such as buffer capacity and pH. A tensammetric
      minimum was not observed for dextran. Our results suggest specific organization
      of biopolymer layers at negative potentials observed only in biomacromolecules
      involved in CHER.

PMID- 29197258
TI  - Prevalence of mild cognitive impairment and its subtypes in community-dwelling
      residents aged 65 years or older in Guangzhou, China.
AB  - BACKGROUND: Prevalence of mild cognitive impairment (MCI) has been reported
      substantial variations, and mostly in Western countries. Less is known about MCI
      in the south of China. The study is to estimate the prevalence of MCI and its
      subtypes in residents aged 65year or older in community-dwelling residents of
      Guangzhou, China. METHODS: The study was a community-based, cross-sectional study
      conducted in rural and urban areas of Guangzhou between April and October 2009.
      Eight communities were randomly selected using a cluster sampling method. Each
      elderly was interviewed with Montreal Cognitive Assessment, the Mini-Mental state
      examination, Auditory Verbal Learning Test, the Clinical Dementia Rating scale et
      al. MCI was classified as amnestic MCI (a-MCI) or nonamnestic MCI (na-MCI).
      RESULTS: 2427 individuals were contacted, but in-person interviews were conducted
      with 2111 participants. 299 participants with MCI were identified. The prevalence
      of MCI, a-MCI and na-MCI was 14.2%, 12.2%, 2.0% respectively. The prevalence of
      MCI and a-MCI increased with age, decreased with education level, and was higher
      in rural areas than in urban areas. The difference of prevalence of MCI and a-MCI
      between women with men wasn't statistically significant(MCIchi2=1.0, OR 0.9,
      95%CI=0.6-1.2; a-MCIchi2=1.0, OR 0.9, 95%CI=0.6-1.2), when controlling for
      education by logistic regression analysis. CONCLUSIONS: The results suggest that
      14.2% of elderly individuals are affected by MCI in Guangzhou, China. And MCI was
      dominated by a-MCI. The prevalence of MCI and a-MCI increased with age, decreased
      with education level, and was higher in the rural population compared to the
      urban population.

PMID- 29197259
TI  - A high sense of coherence protects from the burden of caregiving in older spousal
      caregivers.
AB  - OBJECTIVES: Caregiving is often associated with burden and chronic stress. Sense
      of coherence (SOC) may help the caregivers in coping with their stress and was
      identified as a positive factor for health outcomes and quality of life. We aimed
      to study the links between SOC, burden, depression and positive affects among
      caregivers of frail older patients. METHODS: Seventy-nine spousal caregivers were
      recruited via the geriatric outpatient clinic. DATA COLLECTED: Zarit Burden
      Inventory, SOC-13, Geriatric Depression Scale, Caregiver Reaction Assessment
      (CRA), sleep, time of supervision, Katz Index, Global Deterioration Scale and
      Neuropsychiatric Inventory. ANALYSES: Caregiver's characteristics were analyzed
      by burden severity and SOC level. Multivariable logistic regressions were used in
      order to identify the variable that best predict caregiver burden and high SOC.
      RESULTS: The mean age was 79.4+/-5.3; 53% were women. Among care-recipient, 82%
      had cognitive impairment and the median Katz Index was 3. Caregivers with a high
      SOC and an older age reported a lower burden (Odds Ratio (OR) 0.18, 95%
      confidence interval (CI) 0.04-0.65 and OR 0.87, 95% CI 0.76-0.98, respectively).
      A higher burden was associated with patient functional limitations (OR 8.69, 95%
      CI 2.28-40.46). DISCUSSION: Having a high sense of coherence seems to be a
      protective factor against the burden. To support caregivers, health providers
      should recognize the expertise of the caregivers and the meaningfulness of this
      care situation.

PMID- 29197261
TI  - Is the Clock Drawing Test useful in the screening assessment of aged patients
      with chronic heart failure?
AB  - PURPOSE: Cognitive impairment is one of the most common geriatric deficits in old
      patients with heart failure (HF), but there has been a lack of study on the
      utility of the Clock Drawing Test (CDT) when used with this group of patients.
      The aim of the study was to assess the usefulness of the CDT in the geriatric
      assessment of aged outpatients with chronic HF. PATIENTS AND METHODS: A cross
      sectional analysis of the results of the comprehensive geriatric assessment
      (CGA), including the CDT, of 92 aged outpatients with heart failure was
      conducted. RESULTS: We found a high prevalence of five examined geriatric
      problems. The majority of the patients presented signs of cognitive deterioration
      of different patterns and severity on the Clock Drawing Test. All the CDT scoring
      systems correlated significantly with the Mini-Mental Test Examination results.
      CONCLUSIONS: It seems reasonable to perform the routine CGA with the CDT
      examination in all aged heart failure patients.

PMID- 29197262
TI  - Psychometric evaluation of the Environmental Reality Shock-Related Issues and
      Concerns instrument for newly graduated nurses.
AB  - BACKGROUND: Reality shock is a critical representation of the gap between nursing
      education and clinical practice and it is important to explore the level of
      reality shock among nurses. However, there is no relevant instrument to assess
      the level of reality shock in South Korea. OBJECTIVES: The purpose of this is to
      determine the validity and reliability of the Korean version of the Environmental
      Reality Shock-Related Issues and Concerns instrument. DESIGN: A cross-sectional
      study design was used in this study. SETTINGS: The data collection was conducted
      in selected 15 hospitals in South Korea. PARTICIPANTS: A convenience sample of
      216 newly graduated nurses participated in the study. METHODS: The Korean version
      of the Environmental Reality Shock-Related Issues and Concerns instrument was
      developed through the forward-backward translation technique, and revision based
      on feedback from expert groups. The internal consistency reliability was assessed
      using Cronbach's alpha, and the construct validity was determined via exploratory
      and confirmatory factor analysis. RESULTS: The Korean version of the
      Environmental Reality Shock-Related Issues and Concerns has reliable internal
      consistency (Cronbach's alpha=0.91). Exploratory factor analysis revealed five
      factors including job, relationships, expectations, private life, and
      performance, which explained 61.92% of variance. The factor loadings ranged from
      0.451 to 0.832. The five-factor structure was validated by confirmatory factor
      analysis (RMR<0.05, CFI>0.9). CONCLUSION: It was concluded that the Korean
      version of the Environmental Reality Shock-Related Issues and Concerns instrument
      has satisfactory construct validity and reliability to measure the reality shock
      of newly graduated nurses in South Korea.

PMID- 29197260
TI  - Susceptibility of dendritic cells from individuals with schistosomiasis to
      infection by Leishmania braziliensis.
AB  - Coinfection with leishmaniasis and schistosomiasis has been associated with
      increased time to healing of cutaneous lesions of leishmaniasis. The objective of
      this study was to evaluate the effect of Leishmania braziliensis infection on co
      cultures of monocyte-derived dendritic cells (MoDCs) with autologous lymphocytes
      from patients with schistosomiasis and patients with cutaneous leishmaniasis.
      MoDCs were differentiated from peripheral blood monocytes, isolated by magnetic
      beads, infected with L. braziliensis, and co-cultured with autologous
      lymphocytes. Expression of HLA-DR, CD1a, CD83, CD80, CD86, CD40, and the IL-10
      receptor (IL-10R) on MoDCs as well as CD28, CD40L, CD25, and CTLA-4 on
      lymphocytes were evaluated by flow cytometry. The production of the cytokines IL
      10, TNF, IL-12p40, and IFN-gamma were evaluated by sandwich ELISA of the culture
      supernatant. The infectivity evaluation was performed by light microscopy after
      concentration of cells by cytospin and Giemsa staining. It was observed that the
      frequency of MoDCs expressing CD83, CD80, and CD86 as well as the MFI of HLA-DR
      were smaller in the group of patients with schistosomiasis compared to the group
      of patients with leishmaniasis. On the other hand, the frequency of IL-10R on
      MoDCs was higher in patients with schistosomiasis than in patients with
      leishmaniasis. CD4+ and CD8+ T lymphocytes from patients with schistosomiasis
      presented a lower frequency of CD28 and a higher frequency of CTLA-4 compared to
      lymphocytes from patients with leishmaniasis. Levels of IL-10 were higher in the
      supernatants of co-cultures from individuals with schistosomiasis compared to
      those with leishmaniasis. However, levels of TNF, IL-12p40, and IFN-gamma were
      lower in the group of individuals with schistosomiasis. Regarding the frequency
      of MoDCs infected by L. braziliensis after 72h in culture, it was observed that
      higher frequencies of cells from patients with schistosomiasis were infected
      compared to cells from patients with leishmaniasis. It was concluded that MoDCs
      from patients with schistosomiasis are more likely to be infected by L.
      braziliensis, possibly due to a lower degree of activation and a regulatory
      profile.

PMID- 29197263
TI  - Effects of using mobile device-based academic electronic medical records for
      clinical practicum by undergraduate nursing students: A quasi-experimental study.
AB  - INTRODUCTION: The academic electronic medical record (AEMR) system is applied
      with the expectation that nursing students will be able to attain competence in
      healthcare decision-making and nursing informatics competencies. However, there
      is insufficient evidence regarding the advantage of applying mobile devices to
      clinical practicum. OBJECTIVES: This study aimed to examine the effect of an
      experiment that introduced a mobile AEMR application for undergraduate nursing
      students in their practicum. METHODS: A quasi-experimental design was used. The
      subjects were 75 third-year nursing students enrolled in clinical practicum and
      were divided into an experimental (practicum with AEMR) and a control
      (conventional practicum) group. Nursing informatics competencies, critical
      thinking disposition, and satisfaction with clinical practicum were measured
      before and after the clinical practicum for each group. The usability of the AEMR
      application was also examined for the experimental group after the experiment.
      RESULTS: After the experiment, the experimental group showed a significant
      increase in the informatics knowledge domain of nursing informatics competencies
      in the post-test. The difference in critical thinking between the experimental
      and control groups was not statistically significant. Regarding satisfaction with
      the clinical practicum, the experimental group exhibited a significantly higher
      level of satisfaction in "preparation of a diagnostic test or laboratory test and
      understanding of the results" and "nursing intervention and documentation" than
      the control group. Students who participated in the practicum using the AEMR
      application considered it useful. CONCLUSIONS: The AEMR application was an
      effective educational method for practicing the immediate documentation of
      students' observations and interventions and was available at the patients'
      bedsides. To improve critical thinking, it is necessary to apply a variety of
      approaches when solving clinical problems.

PMID- 29197264
TI  - Blended learning pedagogy designed for communication module among undergraduate
      nursing students: A quasi-experimental study.
AB  - BACKGROUND: Effective communication is important for nurse and patient outcomes.
      Nursing students often feel unprepared to communicate effectively with patients
      and other healthcare workers within the clinical environment. Blended learning
      pedagogy-based communication skills training can provide an alternative to
      traditional methods of teaching to enhance students' satisfaction and self
      efficacy levels in communicating with others. OBJECTIVES: To examine the
      effectiveness of blended learning pedagogy in a redesigned communication module
      among nursing undergraduates in enhancing their satisfaction levels and attitudes
      towards learning communication module as well as self-efficacy in communication.
      DESIGN: A single group pre-test and post-test quasi-experimental design was
      adopted. SETTINGS AND PARTICIPANTS: Data were collected from August 2016 to
      November 2016 from 124 nursing undergraduates from a leading nursing school.
      METHODS: Blended learning pedagogy was adopted to redesign a communication module
      that offered a wide array of learning opportunities via face-to-face classroom
      and online sessions. Validated and reliable instruments were used to measure
      satisfaction levels with blended learning pedagogy, attitudes towards learning
      communication, and communication self-efficacy. Descriptive and inferential
      statistics were used to analyze the data. RESULTS: Participants had enhanced
      satisfaction levels with blended learning pedagogy, better attitudes in learning
      communication skills, and improved communication self-efficacies at posttest
      (week 13 of the semester) when compared with their pre-test scores (week one of
      the semester). Participants scored higher in the Blended Learning Satisfaction
      Scale, the Communication Skills Attitude Scale, and the communication skills
      subscale of the Nursing Students Self-Efficacy Scale. CONCLUSIONS: Blended
      learning pedagogy can be effectively used in facilitating communication modules
      and enhancing student outcomes among nursing undergraduates. The long-term
      effectiveness of using blended learning pedagogy in facilitating communication
      modules should be evaluated from students' and patients' perspectives.
      Additionally, the technology should be constantly improved by incorporating more
      interactive functions and should be tested to accommodate the learners' needs.

PMID- 29197265
TI  - Nasotracheal intubation through pharyngeal flap after pharyngeal flap
      construction.

PMID- 29197266
TI  - Importance of mineral dust and anthropogenic pollutants mixing during a long
      lasting high PM event over East Asia.
AB  - A long-lasting high particulate matter (PM) concentration episode persisted over
      East Asia from May 24 to June 3, 2014. The Nested Air Quality Prediction Model
      System (NAQPMS) was used to investigate the mixing of dust and anthropogenic
      pollutants during this episode. Comparison of observations revealed that the
      NAQPMS successfully reproduced the time series PM2.5 and PM10 concentrations, as
      well as the nitrate and sulfate concentrations in fine (aerodynamic diameter <=
      2.5 MUm) and coarse mode (2.5 MUm < aerodynamic diameter <= 10 MUm). This episode
      originated from two dust events that occurred in the inland desert areas of
      Mongolia and China, and then the long-range transported dust and anthropogenic
      pollutants were trapped over the downwind region of East Asia for more than one
      week due to the blocked north Pacific subtropical high-pressure system over the
      east of Japan. The model results showed that mineral dust accounted for 53-83% of
      PM10, and 39-67% of PM2.5 over five cities in East Asia during this episode.
      Sensitivity analysis indicated that the Qingdao and Seoul regions experienced
      dust and pollution twice, by direct transport from the dust source region and
      from dust detoured over the Shanghai area. The results of the NAQPMS model
      confirmed the importance of dust heterogeneous reactions (HRs) over East Asia.
      Simulated dust NO3- concentrations accounted for 75% and 84% of total NO3- in
      fine and coarse mode, respectively, in Fukuoka, Japan. The horizontal
      distribution of model results revealed that the ratio of dust NO3-/dust
      concentration increased from about 1% over the Chinese land mass to a maximum of
      8% and 6% respectively in fine and coarse mode over the ocean to the southeast of
      Japan, indicating that dust NO3- was mainly formed over the Yellow Sea and the
      East China Sea before reaching Japan.

PMID- 29197267
TI  - Responses of soil nutrients and microbial communities to three restoration
      strategies in a karst area, southwest China.
AB  - Ecological restoration is widespread in the karst region, southwest China, but
      the impacts of different restoration strategies on soil fertility indices have
      rarely been compared. Here soil nutrients and microbial communities were measured
      16 years after agricultural abandonment in a karst area, southwest China. Three
      restoration strategies were included, i.e., i) restoration with an economic tree
      species Toona sinensis (TS), ii) restoration with Guimu-1 hybrid elephant grass
      (GG), iii) restoration with a combination of Zenia insignis and Guimu-1 hybrid
      elephant grass (ZG). Cropland under maize-soybean rotation (CR) was used as
      reference. Soil organic carbon level was more than doubled in TS, and that in GG
      and ZG was elevated by about 50% relative to CR. Soil total nitrogen
      concentration in GG was not significantly different from CR, but that in TS and
      ZG was increased by 93% and 55% relative to CR. Similar to nitrogen, soil total
      phosphorus concentration in GG was not changed relative to CR, but that in TS and
      ZG were significantly increased. Microbial biomass carbon and nitrogen
      concentrations were significantly increased in TS and GG by 124% and 82%,
      respectively, compared to CR, but those in ZG and CR were similar. The abundance
      of total PLFAs (phospholipid fatty acids) was significantly increased by 55-69%
      following agricultural abandonment, and there was no significant difference among
      the three restoration strategies. The patterns of the other microbial groups and
      the ratio of fungal to bacterial (F:B) PLFAs were largely similar to that of
      total PLFAs. Soil organic carbon was identified as the primary factor affecting
      the abundance of soil microbial communities. Our findings suggest that the three
      restoration strategies, particularly TS are efficient in improving soil
      fertility.

PMID- 29197268
TI  - De novo generation of helper virus-satellite chimera RNAs results in disease
      attenuation and satellite sequence acquisition in a host-dependent manner.
AB  - Panicum mosaic virus (PMV) is a helper RNA virus for satellite RNAs (satRNAs) and
      a satellite virus (SPMV). Here, we describe modifications that occur at the 3'
      end of a satRNA of PMV, satS. Co-infections of PMV+satS result in attenuation of
      the disease symptoms induced by PMV alone in Brachypodium distachyon and proso
      millet. The 375 nt satS acquires ~100-200 nts from the 3'-end of PMV during
      infection and is associated with decreased abundance of the PMV RNA and capsid
      protein in millet. PMV-satS chimera RNAs were isolated from native infections of
      St. Augustinegrass and switchgrass. Phylogenetic analyses revealed that the
      chimeric RNAs clustered according to the host species from which they were
      isolated. Additionally, the chimera satRNAs acquired non-viral "linker" sequences
      in a host-specific manner. These results highlight the dynamic regulation of
      viral pathogenicity by satellites, and the selective host-dependent, sequence
      based pressures for driving satRNA generation and genome compositions.

PMID- 29197269
TI  - Anti-tumour necrosis factor-alpha antibodies and B cell homeostasis in human
      inflammatory bowel diseases.
AB  - BACKGROUND: The expression of CD70 on T cells is greatly enhanced by antigen
      presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)
      alpha, which is constitutionally high in patients with inflammatory bowel disease
      (IBD). Experimentally, the chronic activation of CD27 as a result of the
      constitutive expression of CD70 leads to the demise of B cells in bone marrow
      (BM) and the secondary lymphoid organs. The aim of this study was to assess the
      number and phenotype of circulating B cell in untreated IBD patients and their
      counterparts treated with biological anti-TNF drugs. METHODS: The study involved
      13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10
      healthy controls. The B cell phenotypes were assessed by means of flow cytometry
      using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order
      to evaluate B cell development in bone marrow and peripheral B cell activation,
      we identified four B cell subsets: hematogones (HBs: CD20+19+3-27-43+), memory B
      cells (MBs: CD20+19+3-27+43-), pre-plasmablasts (PPBs: CD20+19+3-27+43+), and
      plasmablasts (PBs: CD20-19+3-27+43+). RESULTS: The total number of B cells in the
      untreated patients was three times lower than that in the patients treated with
      biological drug (p<0.001), and half that in the healthy controls (p=0.03). The
      between-group differences (including the healthy donors) were statistically
      significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only
      one treated patient showed a transiently large increase in PPBs. There were
      statistically significant differences in all of the parameters between the
      untreated patients and those receiving biological therapy, and in some cases
      between the untreated patients and healthy controls, but never between the
      controls and the treated patients. Four non-responders to anti-TNF therapy had a
      smaller number of total circulating B cells than the untreated patients.
      CONCLUSIONS: Anti-TNF drugs disinhibit B cell production in IBD patients, but
      maintain the constant homeostasis of circulating B cells. The presence of
      individual variations may allow the activity of anti-TNF drugs to be monitored by
      studying B cell subgroups.

PMID- 29197270
TI  - Photodynamic inactivation of bacteriophage MS2: The A-protein is the target of
      virus inactivation.
AB  - Singlet oxygen mediated oxidation has been shown to be responsible for
      photodynamic inactivation (PDI) of viruses in solution with photosensitisers such
      as 5, 10, 15, 20-tetrakis (1-methyl-4-pyridinio) porphyrin tetra p
      toluenesulfonate (TMPyP). The capsids of non-enveloped viruses, such as
      bacteriophage MS2, are possible targets for viral inactivation by singlet oxygen
      oxidation. Within the capsid (predominantly composed of coat protein), the A
      protein acts as the host recognition and attachment protein. The A-protein has
      two domains; an alpha-helix domain and a beta-sheet domain. The alpha-helix
      domain is attached to the viral RNA genome inside the capsid while the beta-sheet
      domain, which is on the surface of the capsid, is believed to be the site for
      attachment to the host bacteria pilus during infection. In this study, 4 sequence
      specific antibodies were raised against 4 sites on the A-protein. Changes induced
      by the oxidation of singlet oxygen were compared to the rate of PDI of the virus.
      Using these antibodies, our results suggest that the rate of PDI is relative to
      loss of antigenicity of two sites on the A-protein. Our data further showed that
      PDI caused aggregation of MS2 particles and crosslinking of MS2 coat protein.
      However, these inter- and intra-capsid changes did not correlate to the rate of
      PDI we observed in MS2. Possible modes of action are discussed as a means to
      gaining insight to the targets and mechanisms of PDI of viruses.

PMID- 29197271
TI  - Salinity-induced cellular cross-talk in carbon partitioning reveals starch-to
      lipid biosynthesis switching in low-starch freshwater algae.
AB  - Salinity stress has been verified to be a successful approach to enhance lipid
      production in high-starch marine algae, and salinity-induced carbon flow
      switching has been proposed as an algal response specific to brackish water. With
      the aim of testing this assumption, Chlorella sorokiniana SDEC-18, a low-starch
      freshwater alga, was grown in BG11 medium with NaCl addition at various
      concentrations (0, 2, 5, 10, 20, and 30 g/L). The results showed that salinity
      stress promoted carbon redistribution and starch conversion to lipid. The most
      desirable lipid productivity of 19.66 mg/L.d occurred in the medium with 20 g/L
      NaCl, about 2.16 times as high as that in the BG11 medium control. Moreover,
      microalgae with salinity stress were able to produce biodiesel with a more
      suitable cloud point, due to a decrease in the saturated fatty acid content. This
      therefore confirms that low-starch freshwater microalgae can also carry out
      salinity-induced carbon flow switching.

PMID- 29197272
TI  - Efficient synthesis of a (S)-fluoxetine intermediate using carbonyl reductase
      coupled with glucose dehydrogenase.
AB  - (S)-3-chloro-1-phenyl-1-propanol ((S)-CPPO) is an important chiral intermediate
      predominantly used in the synthesis of the chiral side chain of (S)-fluoxetine.
      In this study, carbonyl reductase (CBR) from Novosphingobium aromaticivorans was
      successfully expressed in recombinant E. coli. The enzymatic activity of the
      recombinant CBR was significantly increased to 1875 U/mL in the fed-batch
      fermentation in a 10 L fermenter and recombinant CBR was then purified and
      characterized. By regenerating NADH with glucose dehydrogenase, 100 g/L 3-chloro
      1-phenyl-1-propanone (3-CPP) was successfully converted to (S)-CPPO with a
      conversion of 100% and ee value of 99.6% after 12 h at 30  degrees C in PBS
      buffer (pH 7.0), which are the highest reported to date for the bio-production of
      (S)-CPPO and presented great potential for green production of (S)-CPPO at
      industrial scale.

PMID- 29197273
TI  - Comprehensive evaluation of nitrogen removal rate and biomass, ethanol, and
      methane production yields by combination of four major duckweeds and three types
      of wastewater effluent.
AB  - To assess the potential of duckweeds as agents for nitrogen removal and biofuel
      feedstocks, Spirodela polyrhiza, Lemna minor, Lemna gibba, and Landoltia punctata
      were cultured in effluents of municipal wastewater, swine wastewater, or
      anaerobic digestion for 4 days. Total dissolved inorganic nitrogen (T-DIN) of 20
      50 mg/L in effluents was effectively removed by inoculating with 0.3-1.0 g/L
      duckweeds. S. polyrhiza showed the highest nitrogen removal (2.0-10.8 mg T
      DIN/L/day) and biomass production (52.6-70.3 mg d.w./L/day) rates in all the
      three effluents. Ethanol and methane were produced from duckweed biomass grown in
      each effluent. S. polyrhiza and L. punctata biomass showed higher ethanol (0.168
      0.191, 0.166-0.172 and 0.174-0.191 g-ethanol/g-biomass, respectively) and methane
      (340-413 and 343-408 NL CH4/kg VS, respectively) production potentials than the
      others, which is related to their higher carbon and starch contents and calorific
      values.

PMID- 29197274
TI  - Electronic structure of the BaO molecule with dipole moments and ro-vibrational
      calculations.
AB  - The twenty-three low-lying electronic states (singlet and triplet) of the BaO
      molecule have been studied by using an ab initio method. These electronic states
      have been investigated by using the Complete Active Apace Self-Consistent Field
      (CASSCF) followed by multi-reference configuration interaction (MRCI+Q) with
      Davidson correction. The potential energy curves, the internuclear distance Re,
      the harmonic frequency omegae, the rotational constant Be, the electronic energy
      with respect to the ground state Te and the static and transition dipole moment
      have been investigated. The Einstein spontaneous and induced emission
      coefficients A21 and B21omega as well as the spontaneous radiative lifetime
      tauspon, emission wavelength lambda21 and oscillator strength f21 have been
      calculated by using the transition dipole moment between some doublet electronic
      states. The calculation of the eigenvalues Ev, the rotational constant Bv, the
      centrifugal distortion constant Dv, and the abscissas of the turning points Rmin
      and Rmax have been done by using the canonical functions approach. A very good
      agreement is shown by comparing the values of our work to those found in the
      literature for many electronic states. Eighteen new electronic states have been
      studied here for the first time.

PMID- 29197275
TI  - A sensitive turn on fluorescent probe for detection of biothiols using
      MnO2@carbon dots nanocomposites.
AB  - Presently, the combination of carbon quantum dots (CQDs) and metal oxide
      nanostructures in one frame are being considered for the sensing of purine
      compounds. In this work, a combined system of CQDs and MnO2 nanostructures was
      used for the detection of anticancer drugs, 6-Thioguanine (6-TG) and 6
      Mercaptopurine (6-MP). The CQDs were synthesized through microwave synthesizer
      and the MnO2 nanostructures (nanoflowers and nanosheets) were synthesized using
      facile hydrothermal technique. The CQDs exhibited excellent fluorescence emission
      at 420nm when excited at 320nm wavelength. By combining CQDs and MnO2
      nanostructures, quenching of fluorescence was observed which was attributed to
      fluorescence resonance energy transfer (FRET) mechanism, where CQDs act as
      electron donor and MnO2 act as acceptor. This fluorescence quenching behaviour
      disappeared on the addition of 6-TG and 6-MP due to the formation of Mn-S bond.
      The detection limit for 6-TG (0.015MUM) and 6-MP (0.014MUM) was achieved with the
      linear range of concentration (0-50MUM) using both MnO2 nanoflowers and
      nanosheets. Moreover, the as-prepared fluorescence-sensing technique was
      successfully employed for the detection of bio-thiol group in enapril drug. Thus
      a facile, cost-effective and benign chemistry approach for biomolecule detection
      was designed.

PMID- 29197276
TI  - One-pot radiosynthesis of O-[18F]fluoromethyl-D-tyrosine via intra-molecular
      nucleophilic 18F-fluorination with 1,2,3-triazolium triflate salt precursor.
AB  - A radiolabeled amino acid O-[18F]fluoromethyl-D-tyrosine (D-[18F]FMT) has been
      reported to show high tumor uptake. However, introduction of [18F]fluoromethyl
      group was difficult and was an issue to be solved. We solved it by using a
      precursor containing 1,2,3-triazolium salt. D-[18F]FMT was synthesized from (R)-1
      ((4-(2-((tert-butoxycarbonyl)amino)-3-((3,4-dimethylbenzyl)oxy)-3
      oxopropyl)phenoxy)methyl)-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium
      trifluoromethanesulfonate via intra-molecular 18F-fluorination and subsequent
      removal of the protecting groups. The total synthesis time was 65min (including
      purification) and the overall radiochemical yield was 9% based on the isolated
      product (not decay-corrected). The resulting D-[18F]FMT was obtained with high
      radiochemical purity (> 99%) and specific activity (100-150 GBq/MUmol). D
      [18F]FMT also achieved excellent results in pharmacological evaluation such as
      stability test and protein binding assay. We expect that this simple one-pot
      labeling method would help using D-[18F]FMT more widely.

PMID- 29197277
TI  - Multi-metal nanomaterials obtained from oil/water interface as effective
      catalysts in reduction of 4-nitrophenol.
AB  - In this study Pt and Pd-based nanostructured thin films have been successfully
      fabricated by room temperature self-assembly of metal nanoparticles (NPs) at the
      interface between toluene and water without/with using stabilizers such as
      graphene oxide (GO) or aminoclay (AC). Successful formation of these thin films
      is investigated by transmission electron microscopy (TEM), energy dispersive
      analysis of X-ray (EDAX) and X-ray diffraction (XRD). Catalytic hydrogenation of
      4-nitrophenol (4-NP) to 4-aminophenol (4-AP) was investigated using thin film
      nanocatalysts. The as synthesized nanostructured thin films exhibit high
      catalytic activity toward hydrogenation reaction of 4-NP. This study highlights
      the value of nano alloy thin films and their ability as catalyst in catalytic
      hydrogenation reaction.

PMID- 29197278
TI  - Land use and air quality in urban environments: Human health risk assessment due
      to inhalation of airborne particles.
AB  - Particle matter (PM) and its associated compounds are a serious problem for urban
      air quality and a threat to human health. In the present study, we assessed the
      intraurban variation of PM, and characterized the human health risk associated to
      the inhalation of particles measured on PM filters, considering different land
      use areas in the urban area of Cordoba city (Argentina) and different age groups.
      To assess the intraurban variation of PM, a biomonitoring network of T.
      capillaris was established in 15 sampling sites with different land use and the
      bioaccumulation of Co, Cu, Fe, Mn, Ni, Pb and Zn was quantified. After that,
      particles were collected by instrumental monitors placed at the most
      representative sampling sites of each land use category and an inhalation risk
      was calculated. A remarkable intraurban difference in the heavy metals content
      measured in the biomonitors was observed, in relation with the sampling site land
      use. The higher content was detected at industrial areas as well as in sites with
      intense vehicular traffic. Mean PM10 levels exceeded the standard suggested by
      the U.S. EPA in all land use areas, except for the downtown. Hazard Index values
      were below EPA's safe limit in all land use areas and in the different age
      groups. In contrast, the carcinogenic risk analysis showed that all urban areas
      exceeded the acceptable limit (1 * 10-6), while the industrial sampling sites and
      the elder group presented a carcinogenic risk higher that the unacceptable limit.
      These findings validate the use of T. capillaris to assess intraurban air quality
      and also show there is an important intraurban variation in human health risk
      associated to different land use.

PMID- 29197279
TI  - Trends in the consecutive days of temperature and precipitation extremes in China
      during 1961-2015.
AB  - BACKGROUND AND AIMS: Consecutive climatic extremes have more intense impacts on
      natural ecosystems and human activities than occasional events. There were many
      studies about the frequency or intensity of extreme weather events, but few
      focused on the consecutiveness or continuousness of climatic extremes. We
      analyzed the temporal and spatial distributions and tendencies in the consecutive
      temperature and precipitation extremes in China during 1961-2015. METHODS: Daily
      temperature and precipitation data at 1867 meteorological stations over China was
      used and four consecutive indices of climate extremes, i.e. cold spell duration
      indicator (CSDI), warm spell duration indicator (WSDI), consecutive dry days
      (CDD) and consecutive wet days (CWD), were calculated by RClimDex 1.0. Linear
      trends in the time series of consecutive days of temperature and precipitation
      extremes were examined and their statistical significance was evaluated using
      Mann-Kendall test. RESULTS AND DISCUSSION: There were obvious differences in the
      spatial distributions of consecutive days of climate extremes in China. During
      1961-2015, CSDI and CWD decreased significantly at rates of 0.9 and 0.1 days per
      decade respectively, while WSDI increased significantly at rate of 0.8 days per
      decade in China. Spatially, CSDI decreased at rates of 0-3.0 days per decade in
      almost all parts of China, and WSDI increased at rates of 0-2.0 days per decade
      in most parts of China. The spatial trends of CDD and CWD were significant only
      in several regions of China. CSDI and WSDI had higher percent changes than those
      of CDD and CWD. Changes in the CSDI and WSDI were associated with large-scale
      oceanic and atmospheric circulation oscillations, such as Atlantic Multidecadal
      Oscillation (AMO), El Nino/Southern Oscillation (ENSO) and Pacific Decadal
      Oscillation (PDO). With global warming, there will be fewer cold extremes, more
      frequent hot extremes and precipitation extremes. CONCLUSIONS: Given the
      increases in the frequency and intensity of some consecutive climatic extremes
      and an increasing physical exposure and socio-economic vulnerability to such
      extremes in China, more strategies and capacities of mitigation and adaptation to
      consecutive climatic extremes are essential for the local government and climate
      sensitive sectors.

PMID- 29197280
TI  - Occurrence of cyclic imines in European commercial seafood and consumers risk
      assessment.
AB  - Cyclic imines constitute a quite recently discovered group of marine biotoxins
      that act on neural receptors and that bioaccumulate in seafood. They are grouped
      together due to the imino group functioning as their common pharmacore,
      responsible for acute neurotoxicity in mice. Cyclic imines (CIs) have not been
      linked yet to human poisoning and are not regulated in the European Union (EU),
      although the European Food Safety Authority (EFSA) requires more data to perform
      conclusive risk assessment for consumers. Several commercial samples of bivalves
      including raw and processed samples from eight countries (Italy, Portugal,
      Slovenia, Spain, Ireland, Norway, The Netherlands and Denmark) were obtained over
      2 years. Emerging cyclic imine concentrations in all the samples were analysed on
      a LC-3200QTRAP and LC-HRMS QExactive mass spectrometer. In shellfish, two CIs,
      pinnatoxin G (PnTX-G) and 13-desmethylspirolide C (SPX-1) were found at low
      concentrations (0.1-12ug/kg PnTX-G and 26-66ug/kg SPX-1), while gymnodimines and
      pteriatoxins were not detected in commercial (raw and processed) samples. In
      summary, SPX-1 (n: 47) and PnTX-G (n: 96) were detected in 9.4% and 4.2% of the
      samples, respectively, at concentrations higher than the limit of quantification
      (LOQ), and in 7.3% and 31.2% of the samples at concentrations lower than the LOQ
      (25ug/kg for SPX-1 and 3ug/kg for PnTX-G), respectively. For the detected cyclic
      imines, the average exposure and the 95th percentile were calculated. The results
      obtained indicate that it is unlikely that a potential health risk exists through
      the seafood diet for CIs in the EU. However, further information about CIs is
      necessary in order to perform a conclusive risk assessment.

PMID- 29197281
TI  - Trends in peri-operative performance status following resection of high grade
      glioma and brain metastases: The impact on survival.
AB  - OBJECTIVES: Maximal surgical resection of high grade brain tumours is associated
      with improved overall survival (OS). It carries the risk of neurological
      deterioration leading to worsening performance status (PS), which may affect
      overall survival and preclude patients from adjuvant therapy. We aim to review
      the changes in performance status of patients undergoing resection of high grade
      tumours and metastases and the impact of changes on overall survival. PATIENTS
      AND METHODS: A prospective study of the perioperative performance status of 75
      patients who underwent primary resection of malignant primary brain tumour or
      solitary metastasis in a single centre. Data on patients' demographics, tumour
      histology and overall survival were also collected. WHO performance status was
      recorded pre-operatively and at intervals following surgery. RESULTS: Of the 75
      patients (35 males, 40 females, median age 61 years at diagnosis), 50 had primary
      malignant brain tumours, 25 had metastasis. Although PS dropped at postoperative
      day 1 in 14 patients (18.7%), 28% improved by day 5 and there was significant
      improvement by day 14 (41%, p=0.02). The number of patients with PS 3 or worse
      changed from 4% pre-operatively (n=3) to 8% (n=6). Overall survival is better in
      those whose PS remained improved or unchanged at 2 weeks after surgery compared
      to those whose PS deteriorated; high grade glioma median survival 15.67 vs. 2.4
      months (p=0.005) and metastasis median survival 8.53 vs.2.33 months (p=0.001).
      CONCLUSION: Our data demonstrates that although PS may deteriorate immediately
      after surgery, the majority of patients regain their baseline PS or improve by 2
      weeks postoperatively; decisions on fitness for adjuvant treatment should
      therefore be delayed until then. In those patients whose PS declines following
      surgery overall survival is poor.

PMID- 29197282
TI  - Biofunctionalized silicon nitride platform for sensing applications.
AB  - Silicon nitride (SiNx) based biosensors have the potential to converge on the
      technological achievements of semiconductor microfabrication and biotechnology.
      Development of biofunctionalized SiNx surface and its integration with other
      devices will allow us to integrate the biosensing capability with probe control,
      data acquisition and data processing. Here we use the hydrogen plasma generated
      by inductively coupled plasma-reactive ion etching (ICP-RIE) technique to produce
      amino-functionality on the surface of SiNx which can then be readily used for
      biomolecule immobilization. ICP-RIE produces high-density hydrogen ions/radicals
      at low energy, which produces high-density amino group on the SiNx surface within
      a short duration of time and with minimal surface damage. In this work, we have
      demonstrated selective amination of SiNx surface as compared to Si surface. The
      as-activated SiNx surface can be readily biofunctionalized with both protein and
      oligonucleotide through covalent immobilization. N-5-azido-2
      nitrobenzoyloxysuccinimide, a photoactivable amino reactive bifunctional
      crosslinker, was used and greater than 90% surface coverage was achieved for
      protein immobilization. In addition, ssDNA immobilization and hybridization with
      its complemented strand was shown. Thus, we demonstrate a uniform, reliable, fast
      and economical technique for creating biofunctionalized SiNx surface that can be
      used for developing compact high-sensitivity biosensors.

PMID- 29197283
TI  - The dose makes the poison.
AB  - Some microcystins (MCs) might cause hepatotoxicity in animals and humans. MC-LR
      is also a tumor promoter and a suspect carcinogen. In 2010, the International
      Agency for Research on Cancer (IARC) classified MC-LR as a possible human
      carcinogen (Group 2B). Recently, an article entitled "Long-term, low-dose
      exposure to microcystin toxin does not increase the risk of liver tumor
      development or growth in mice" was published in Hepatology Research by Meaghan
      Labine and Gerald Y. Minuk. However, the experimental design was flawed and the
      conclusion is misleading. 1MUg/L MC-LR in drinking water is the provisional
      guideline value established by the World Health Organization (WHO) for humans in
      1998, based on a tolerable daily intake (TDI) of 0.04MUg/kg body mass (BM).
      Assuming the mice drink 1.5mL/10g BM of water per day, the exposure dose would be
      0.15MUg/kg/d BM, about 270-fold less than 40MUg/kg/d, the no-observed-adverse
      effect level (NOAEL). Thus, the dose of MC-LR was too small and "unlikely to
      result in liver tumor development or enhance existing tumor growth", even with a
      long-term (28weeks) exposure. Presumably, they didn't consider inter-species
      variations between mice and humans, including toxicokinetics and toxicodynamics.
      Ranges of "low-dose" MCs for animals and humans should be defined. Also, the
      authors misunderstood or misrepresented several previous studies. Before drawing
      final conclusions on the carcinogenicity of MCs, further well-designed
      experiments are warranted.

PMID- 29197284
TI  - Detection of PPCPs in marine organisms from contaminated coastal waters of the
      Saudi Red Sea.
AB  - The occurrence of PPCPs in macroalgae, barnacle and fish samples from
      contaminated coastal waters of the Saudi Red Sea is reported. Solvent extraction
      followed by solid phase extraction was applied to isolate the compounds, and
      their quantification was carried out by high performance liquid chromatography
      tandem mass spectrometry. Atenolol, ranitidine, chlorpheniramine, DEET, and
      atrazine were detected in one or more macroalgae at <LOQ concentration, whereas
      caffeine, methylparaben, and carbamazepine were present atmaximum concentrations
      of 41.3, 44.3, and 1.7ng/g (on a dry weight basis=dw), respectively. Eleven PPCPs
      were detected in the barnacle samples at concentrations between <LOQ and maximum
      concentration of 17.9ng/g dw for amitriptyline. Furthermore, 17 compounds were
      detected in several or all of the five fish species studied with a maximum
      concentration of 82.1ng/g dw for metronidazole in Silver Biddy. The
      bioaccumulation factors (BAF) for selected PPCPs were determined and compared.
      The occurrence and enrichment of PPCPs in macroalgae and barnacles might indicate
      that a new route for uptake of such chemicals by marine biota is available,
      specifically in contaminated waters where a continuous supply of non-persistent
      contaminants such as PPCPs is available for long-term exposure of local benthic
      organisms.

PMID- 29197285
TI  - Fresh carbon inputs to seagrass sediments induce variable microbial priming
      responses.
AB  - Microbes are the 'gatekeepers' of the marine carbon cycle, yet the mechanisms for
      how microbial metabolism drives carbon sequestration in coastal ecosystems are
      still being defined. The proximity of coastal habitats to runoff and disturbance
      creates ideal conditions for microbial priming, i.e., the enhanced
      remineralisation of stored carbon in response to fresh substrate availability and
      oxygen introduction. Microbial priming, therefore, poses a risk for enhanced CO2
      release in these carbon sequestration hotspots. Here we quantified the existence
      of priming in seagrass sediments and showed that the addition of fresh carbon
      stimulated a 1.7- to 2.7-fold increase in CO2 release from recent and accumulated
      carbon deposits. We propose that priming taking place at the sediment surface is
      a natural occurrence and can be minimised by the recalcitrant components of the
      fresh inputs (i.e., lignocellulose) and by reduced metabolism in low oxygen and
      high burial rate conditions. Conversely, priming of deep sediments after the
      reintroduction to the water column through physical disturbances (e.g., dredging,
      boat scars) would cause rapid remineralisation of previously preserved carbon.
      Microbial priming is identified as a process that weakens sediment carbon storage
      capacity and is a pathway to CO2 release in disturbed or degraded seagrass
      ecosystems; however, increased management and restoration practices can reduce
      these anthropogenic disturbances and enhance carbon sequestration capacity.

PMID- 29197286
TI  - The two faces of Janus, or the dual mode of public attitudes towards snakes.
AB  - Snakes are controversial animals, therefore a better understanding of public
      attitudes is critical for their effective protection and future survival. The
      attitudes towards snakes of 951 adults in Greece were investigated in personal
      interviews. Factor analysis revealed a dual mode of attitudes: respondents were
      highly intolerant of snakes, while they supported their conservation at the same
      time. Respondents had high knowledge about the behavior of snakes, medium
      knowledge of their biology and were strongly affected by folklore. Structural
      models revealed that tolerance was a positive mediator of conservation. Knowledge
      about snake behavior and biology was positively correlated with attitudes towards
      snakes. Moralistic and naturalistic attitudes were positively, and dominionistic
      attitudes negatively, correlated with snake tolerance and conservation attitudes.
      Younger, more educated people were more snake-tolerant than older, less educated
      people. Females were less snake-tolerant and more conservation-oriented than
      males. These findings increased the understanding of human attitudes towards
      snakes and helped identify factors critical for their conservation. As such they
      could be used to design environmental education programs incorporating both
      information-based and experiential activities that will improve attitudes,
      behaviors and, eventually, the chances for the survival of these uncharismatic
      animals.

PMID- 29197287
TI  - Assessing the relationship between the abundance and properties of microplastics
      in water and in mussels.
AB  - Microplastic pollution is increasingly becoming a great environmental concern
      worldwide. Microplastics have been found in many marine organisms as a result of
      increasing plastic pollution within marine environments. However, the
      relationship between micoplastics in organisms and their living environment is
      still relatively poorly understood. In the present study, we investigated
      microplastic pollution in the water and the mussels (Mytilus edulis, Perna
      viridis) at 25 sites along the coastal waters of China. We also, for the first
      time, conducted an exposure experiment in parallel on the same site using M.
      edulis in the laboratory. A strong positive linear relationship was found between
      microplastic levels in the water and in the mussels. Fibers were the dominant
      microplastics. The sizes of microplastics in the mussels were smaller than those
      in the water. During exposure experiments, the abundance of microbeads was
      significantly higher than that of fibers, even though the nominal abundance of
      fibers was eight times that of microbeads. In general, our results supported
      positive and quantitative correlations of microplastics in mussels and in their
      surrounding waters and that mussels were more likely to ingest smaller
      microplastics. Laboratory exposure experiment is a good way to understand the
      relative impacts of microplastics ingested by marine organisms. However,
      significant differences in the results between exposure experiments and field
      investigations indicated that further efforts are needed to simulate the diverse
      environmentally relevant properties of microplastics.

PMID- 29197288
TI  - Superparamagnetic iron oxides nanoparticles from municipal solid waste
      incinerators.
AB  - During their production, management, and landfilling, bottom (BA) and fly (FA)
      ashes from municipal solid waste incineration may liberate Fe-bearing, ultrafine
      particles and easily enter different environmental sinks of the biosphere. We aim
      to explore a collection of BA and FA samples from Italian incinerators to probe
      magnetic mineralogy and the fraction of harmful superparamagnetic (SP)
      nanoparticles (d<30nm). X-ray diffraction, electron microscopy observation,
      temperature- and frequency-dependent magnetometry, and Mossbauer analysis are
      performed. The integration of information from our rock magnetic and non-magnetic
      techniques leads us to conclude that the dominant magnetic carrier in our samples
      is magnetite and its intermediate/impure forms, while sulphides (i.e., monoclinic
      pyrrhotite) are important ancillary magnetic phases. The SP fraction fluxing from
      the BA and FA outputs of a single incinerator is detected and estimated in
      103tons/year. This work stresses the need to calibrate the current technologies
      towards a safer management of combustion ashes and certainly to inform the
      environmental impact assessment by using a combination of different methods.

PMID- 29197289
TI  - Mapping groundwater contamination risk of multiple aquifers using multi-model
      ensemble of machine learning algorithms.
AB  - Constructing accurate and reliable groundwater risk maps provide scientifically
      prudent and strategic measures for the protection and management of groundwater.
      The objectives of this paper are to design and validate machine learning based
      risk maps using ensemble-based modelling with an integrative approach. We employ
      the extreme learning machines (ELM), multivariate regression splines (MARS), M5
      Tree and support vector regression (SVR) applied in multiple aquifer systems
      (e.g. unconfined, semi-confined and confined) in the Marand plain, North West
      Iran, to encapsulate the merits of individual learning algorithms in a final
      committee-based ANN model. The DRASTIC Vulnerability Index (VI) ranged from 56.7
      to 128.1, categorized with no risk, low and moderate vulnerability thresholds.
      The correlation coefficient (r) and Willmott's Index (d) between NO3
      concentrations and VI were 0.64 and 0.314, respectively. To introduce
      improvements in the original DRASTIC method, the vulnerability indices were
      adjusted by NO3 concentrations, termed as the groundwater contamination risk
      (GCR). Seven DRASTIC parameters utilized as the model inputs and GCR values
      utilized as the outputs of individual machine learning models were served in the
      fully optimized committee-based ANN-predictive model. The correlation indicators
      demonstrated that the ELM and SVR models outperformed the MARS and M5 Tree
      models, by virtue of a larger d and r value. Subsequently, the r and d metrics
      for the ANN-committee based multi-model in the testing phase were 0.8889 and
      0.7913, respectively; revealing the superiority of the integrated (or ensemble)
      machine learning models when compared with the original DRASTIC approach. The
      newly designed multi-model ensemble-based approach can be considered as a
      pragmatic step for mapping groundwater contamination risks of multiple aquifer
      systems with multi-model techniques, yielding the high accuracy of the ANN
      committee-based model.

PMID- 29197290
TI  - Simulating water quality and ecological status of Lake Vansjo, Norway, under land
      use and climate change by linking process-oriented models with a Bayesian
      network.
AB  - Excess nutrient inputs and climate change are two of multiple stressors affecting
      many lakes worldwide. Lake Vansjo in southern Norway is one such eutrophic lake
      impacted by blooms of toxic blue-green algae (cyanobacteria), and classified as
      moderate ecological status under the EU Water Framework Directive. Future climate
      change may exacerbate the situation. Here we use a set of chained models (global
      climate model, hydrological model, catchment phosphorus (P) model, lake model,
      Bayesian Network) to assess the possible future ecological status of the lake,
      given the set of climate scenarios and storylines common to the EU project MARS
      (Managing Aquatic Ecosystems and Water Resources under Multiple Stress). The
      model simulations indicate that climate change alone will increase precipitation
      and runoff, and give higher P fluxes to the lake, but cause little increase in
      phytoplankton biomass or changes in ecological status. For the storylines of
      future management and land-use, however, the model results indicate that both the
      phytoplankton biomass and the lake ecological status can be positively or
      negatively affected. Our results also show the value in predicting a biological
      indicator of lake ecological status, in this case, cyanobacteria biomass with a
      BN model. For all scenarios, cyanobacteria contribute to worsening the status
      assessed by phytoplankton, compared to using chlorophyll-a alone.

PMID- 29197291
TI  - Induced sperm oxidative stress in dogs: Susceptibility against different reactive
      oxygen species and protective role of seminal plasma.
AB  - Oxidative stress (OS) is characterized by an unbalance between increased levels
      of reactive oxygen species (ROS) and/or impaired antioxidant protection. In this
      context, the composition of seminal plasma (SP) plays a key role in protecting
      sperm against OS. However, reproductive biotechnologies applied to dogs recommend
      the removal of SP. Thus, antioxidant therapy may be an important alternative when
      applying biotechniques such as semen cryopreservation in this specie. However, in
      order to be efficient, the choice of the ideal antioxidant in each condition is
      essential since each ROS is preferably neutralized by different antioxidant
      systems. Therefore, this study aims to evaluate the susceptibility of canine
      spermatozoa to different oxidative challenges (superoxide anion [O2-], hydrogen
      peroxide [H2O2], hydroxyl radical [OH-] and malondialdehyde [MDA]) in the present
      or absence of SP. We used ejaculates of eight dogs and submitted to induce
      oxidative challenges (with or without SP). After incubations, samples were
      evaluated for the susceptibility to lipid peroxidation, motility, mitochondrial
      activity and function, DNA integrity, plasma membrane and acrosome integrity.
      Sperm with SP had mitochondrial function preserved against ROS. However, in the
      absence of SP, H2O2 reduced mitochondrial membrane potential. In addition,
      regardless on SP, H2O2 was deleterious to sperm kinetics and plasma/acrosomal
      membranes. Incubation with OH- reduced mitochondrial activity and increased DNA
      fragmentation also independent on the absence of presence of SP. Furthermore,
      samples with SP were more resistant to lipid peroxidation (i.e., decreased
      concentration of TBARS). In conclusion, H2O2 and OH- appears to be the most
      deleterious ROS to dog sperm and SP protects the spermatozoa against
      mitochondrial injuries and lipid peroxidation.

PMID- 29197292
TI  - Expression and regulation of inhibitor of DNA binding proteins ID1, ID2, ID3, and
      ID4 at the maternal-conceptus interface in pigs.
AB  - Inhibitor of DNA binding (ID) proteins, ID1, ID2, ID3, and ID4 are
      transcriptional regulators that have a helix-loop-helix (HLH) domain but not a
      basic DNA binding domain. ID proteins inhibit the functions of basic HLH
      transcription factors and regulate cell proliferation and differentiation.
      However, the expression and function of ID1, ID2, ID3, and ID4 at the maternal
      conceptus interface are not fully understood in pigs. Therefore, we determined
      the expressions of ID1, ID2, ID3, and ID4 in porcine endometrium, conceptus, and
      chorioallantoic tissues. ID1, ID2, ID3, and ID4 mRNAs were expressed in the
      endometrium, with lower levels of ID1, ID2, and ID4 on Day 12 of pregnancy than
      during the estrous cycle. ID1, ID2, ID3, and ID4 mRNAs were also detected in
      conceptus and chorioallantoic tissues during pregnancy. ID2 protein was mainly
      localized to luminal epithelia and weakly to vascular smooth muscle cells in the
      endometrium and conceptus trophectoderm. Increasing doses of interleukin-1beta
      decreased levels of ID2 mRNA, while estradiol-17beta increased levels of ID3 mRNA
      in endometrial explants. The expressions of ID2 and ID4 mRNAs were higher in
      endometria from gilts with somatic cell nuclear transfer-derived conceptuses
      compared with endometria from gilts carrying conceptuses derived from natural
      mating on Day 12. These results indicate that the expressions of ID family genes
      are dynamically regulated at the maternal-conceptus interface, suggesting that ID
      proteins may play critical roles in the regulation of endometrial epithelial cell
      function and conceptus development to support the establishment and maintenance
      of pregnancy in pigs.

PMID- 29197293
TI  - Synergistic effect of cysteamine, leukemia inhibitory factor, and Y27632 on goat
      oocyte maturation and embryo development in vitro.
AB  - Goat oocyte in vitro maturation is associated with a variable efficiency of
      embryo development after in vitro fertilization (IVF). Here, we developed a novel
      maturation procedure to evaluate the cellular effect of cysteamine (Cys),
      leukemia inhibitory factor (LIF) and Y27632 on oocyte in vitro maturation in
      native Chinese Yangtze river white goats. Oocytes were collected by slicing ovary
      tissues and matured for 24 h in vitro prior to IVF. Presumptive fertilized
      oocytes were cultured in embryo media for 8 days. Maturation rates were similar
      in gonadotropin basal maturation medium and the same medium supplemented with
      Cys, LIF, or Y27362 (41.0-48.0%; P > 0.05). However, when two substances were co
      supplemented into the medium, the maturation rate was higher in the Cys+LIF group
      than in the LIF+Y27362 and Cys+Y27362 groups (60.0% vs. 43.1% and 25.8%,
      respectively; P < 0.05). Co-supplementation of all three substances into the
      medium achieved the highest maturation rate (67.5%; P < 0.05). Compared with
      oocytes in gonadotropin basal maturation medium, those in medium supplemented
      with Cys showed increased fertilization (56.1% vs. 72.1%), cleavage (36.7% vs.
      44.8%), and blastocyst development (1.7% vs. 4.2%), respectively (P < 0.05).
      Cys+LIF supplementation further improved fertilization (81.6%), cleavage (54.9%),
      and blastocyst development (6%; P < 0.05). Furthermore, combined supplementation
      of all three substances resulted in the best fertilization (84.9%), cleavage
      (70.7%), and blastocyst development (10.3%; P < 0.05). Resultant IVF blastocysts
      possessed an average cell number as high as 276 +/- 45 per embryo. This is the
      first study to report increased efficiency of caprine oocyte maturation by
      combined Cys, LIF, and Y27632 supplementation into basal maturation medium,
      leading to improved fertilization and embryo development in vitro post-IVF.

PMID- 29197294
TI  - Gestational ultrasonography and Dopplerfluxometry in capuchin monkeys (Sapajus
      apella) zoometric.
AB  - The objectives of the current study were as follows: 1) to evaluate blood flow in
      the uterine (UA) and umbilical (Uma) arteries in pregnant capuchin monkeys by
      measuring the resistive index (RI) and pulsatility index (PI); 2) to determine
      the presence or absence of the early diastolic notch and diastolic flow in the UA
      and Uma flow waveforms, respectively; 3) to perform conceptus echobiometry for
      fetal growth assessment during pregnancy; 4) to describe the moment that the
      fetal organs were initially observed; and 5) to determine when the diagnosis of
      fetal gender is possible. Seven healthy, sexually mature female Sapajus apella
      were examined in Weeks -20 to -1 before whelping (whelping Week 0). Triplex
      Doppler was used to assess the blood flow and fetal heart rate, and B-mode
      ultrasonography was used to assess the fetal organs and conceptus measurements,
      including the gestational sac latero-lateral longitudinal (LLL) and latero
      lateral transversal (LLT), the crown rump length (CRL), biparietal diameter
      (BPD), occipito-frontal diameter (OFD), head circumference (HC), abdominal
      circumference (AC), femur length (FL) and fetal organ. All the pregnancies ended
      with a normal whelping and the birth of a live newborn. Prior to whelping, all
      conceptus dimensions increased significantly, whereas the RI and PI of both the
      UA and Uma decreased significantly. For the UA, the RI and PI were (mean +/- SEM)
      0.835 +/- 0.017 and 2.157 +/- 0.129, 0.808 +/- 0.008 and 1.920 +/- 0.041, and
      0.761 +/- 0.006 and 1.759 +/- 0.036 on periods -3, -2 and -1, respectively. For
      the Uma, the RI and PI were 0.97 +/- 0.01 and 2.50 +/- 0.02 at Week -17 and were
      0.64 +/- 0.02 and 0.98 +/- 0.04 at Week -1, respectively. The complete
      disappearance of the early diastolic notch in the UA, and the complete appearance
      of diastolic flow in the Uma occurred on Week -1 and Week -11, respectively.
      Linear regression analyses regarding the relationship of the weeks before
      whelping (WBW) with the conceptus parameters were as follows: CRL = 16.93 + 0.93
      WBW and FL = 3.62 + 0.22 WBW (R2 = 0.98, P < 0.0001); AC = 13.46 + 0.67 WBW (R2 =
      0.96, P < 0.0001); BPD = 4.46 + 0.20 WBW (R2 = 0.95, P < 0.0001); LLL = 11.46 +
      0.45 WBW, LLT = 9.52 + 0.38 WBW and HC = 16.68 + 0.80 WBW (R2 = 0.92, P <
      0.0001); Uma RI = 0.64-0.02 WBW and PI = 0.79-0.11 WBW (R2 = 0.90, P < 0.0001);
      and OFD = 5.84 + 0.27 WBW (R2 = 0.86, P < 0.0001). The authors concluded that for
      fetal echobiometry UA and Uma perfusion were important endpoints to assess fetal
      vitality in the capuchin monkey. Moreover, it was possible to describe the moment
      when the organs were visualized and perform sexing.

PMID- 29197295
TI  - Reproductive aging in male dogs: The epididymal sperm defects and expression of
      androgen receptor in reproductive tissues.
AB  - The present study aimed at investigating age-related changes in epididymal sperm
      motility, morphology, DNA integrity and androgen receptor (AR) expression in
      canine reproductive tissues. Fifty-five healthy medium-sized male dogs were
      divided into four groups: young (1 - 3 years old, n = 14), adult (>3 - 6 years
      old, n = 12), old (>6 - 9 years old, n = 14) and senile (>9 years old, n = 15).
      After routine castration, testes, epididymides (head, body and tail) and vas
      deferens were collected. Spermatozoa were flushed from epididymal tails and their
      motility, morphology and DNA integrity were examined. Localization of AR was
      investigated by immunohistochemistry and the positive immunostaining cells were
      evaluated using image analysis software (NuclearQuant, 3DHISTECH). We found
      significantly lower percentages of epididymal sperm motility, sperm vigour and
      viability in adult, old and senile dogs in comparison with young dogs (p < 0.05).
      Animal's age negatively correlated with epididymal sperm motility, sperm vigour
      and viability. The primary, secondary, major and minor epididymal sperm defects
      were significantly higher in senile dogs compared to young dogs. There were
      positive correlations between age and epididymal sperm defects (p < 0.01). The
      percentage of sperm with fragmented DNA did not differ between age groups.
      Testicular AR was expressed in the nucleus of Sertoli cells, Leydig cells and
      peritubular myoid cells, except for germ cells. Expression of AR was found in all
      epithelium, lamina propria and smooth muscle cells of the epididymis and vas
      deferens. Expression levels of AR in testis, epididymis and vas deferens did not
      differ between age groups (p > 0.05). In conclusion, the present study clearly
      demonstrated that senescence in dogs was associated with decreased epididymal
      sperm quality. An age-related increase in the incidence of poor epididymal sperm
      quality may promote subfertility, especially in senile dogs.

PMID- 29197296
TI  - Genetic analysis of age at first calving, accumulated productivity, stayability
      and mature weight of Nellore females.
AB  - The female reproductive performance, productivity and size are strongly
      associated with production efficiency of herds raised in a tropical environment.
      The age at first calving (AFC), accumulated productivity (AP), stayability (STAY)
      and mature weight (MW) could be used as indicators of these traits. In this
      study, the genetic parameters and correlations between AFC, AP, STAY and MW
      measured in Nellore females were estimated, in order to provide support for the
      beef cattle evaluation programs. In addition, the genetic changes for these
      traits were obtained. The (co)variance components were estimated by Gibbs
      sampling by four-trait multivariate analysis, using a threshold animal model for
      STAY and linear animal model for the other traits (AFC, AP and MW). Heritability
      of AFC, AP and STAY showed low values, with posterior means of 0.13 +/- 0.02,
      0.14 +/- 0.01 and 0.19 +/- 0.03, respectively. On the other hand, for MW were
      estimated mean heritability of 0.44 +/- 0.03 and repeatability of 0.77 +/- 0.03,
      demonstrating the importance of genetic and permanent environmental effects for
      the expression of beef cows' size. The AFC showed null genetic correlation with
      AP (-0.06 +/- 0.12) and MW (0.01 +/- 0.09) and low and negative with STAY (-0.15
      +/- 0.11). The AP showed high genetic correlation with STAY (0.86 +/- 0.03) and
      weak with MW (0.23 +/- 0.09). Positive and moderate genetic association was
      estimated between STAY and MW (0.66 +/- 0.05). Annual direct genetic trends of
      0.19 kg, 0.30 units and 0.10 kg were estimated for AP, STAY and MW, respectively,
      and were significant (P < 0.05) for STAY and MW. For AFC, negative and favorable
      annual genetic change was estimated (-0.08 months, P < 0.05). In this population,
      the selection of heifers for an early reproductive age should have little
      influence, however favorable, in the time that the cows remain in the herd. The
      use of AP as a selection criterion should result in smaller changes in the
      females' mature weight when compared to selection based on STAY.

PMID- 29197297
TI  - Use of chemometrics to compare NIR and HPLC for the simultaneous determination of
      drug levels in fixed-dose combination tablets employed in tuberculosis treatment.
AB  - The World Health Organization recommends that TB treatment be administered using
      combination therapy. The methodologies for quantifying simultaneously associated
      drugs are highly complex, being costly, extremely time consuming and producing
      chemical residues harmful to the environment. The need to seek alternative
      techniques that minimize these drawbacks is widely discussed in the
      pharmaceutical industry. Therefore, the objective of this study was to develop
      and validate a multivariate calibration model in association with the near
      infrared spectroscopy technique (NIR) for the simultaneous determination of
      rifampicin, isoniazid, pyrazinamide and ethambutol. These models allow the
      quality control of these medicines to be optimized using simple, fast, low-cost
      techniques that produce no chemical waste. In the NIR - PLS method, spectra
      readings were acquired in the 10,000-4000cm-1 range using an infrared
      spectrophotometer (IRPrestige - 21 - Shimadzu) with a resolution of 4cm-1, 20
      sweeps, under controlled temperature and humidity. For construction of the model,
      the central composite experimental design was employed on the program Statistica
      13 (StatSoft Inc.). All spectra were treated by computational tools for
      multivariate analysis using partial least squares regression (PLS) on the
      software program Pirouette 3.11 (Infometrix, Inc.). Variable selections were
      performed by the QSAR modeling program. The models developed by NIR in
      association with multivariate analysis provided good prediction of the APIs for
      the external samples and were therefore validated. For the tablets, however, the
      slightly different quantitative compositions of excipients compared to the
      mixtures prepared for building the models led to results that were not
      statistically similar, despite having prediction errors considered acceptable in
      the literature.

PMID- 29197298
TI  - Pharmacokinetics and tissue distribution study of 10-methoxycamptothecin in rats
      following intragastric administration.
AB  - Natural bioactive derivatives of camptothecin (CPT), 10-methoxycamptothecin
      (MCPT) and 10-hydroxycamptothecin (HCPT) have been confirmed to possess high
      antitumor activities. MCPT could be metabolized to HCPT in vivo. The HPLC method
      for the quantification of MCPT and HCPT was established and validated, and the
      pharmacokinetics and the tissue distribution of MCPT in rats after i.v.
      administration have been well carried out in our previous studies. To improve the
      further understanding of the in vivo behavior of MCPT, a rapid and sensitive UPLC
      MS/MS method was developed and validated for the quantification of MCPT and HCPT
      in plasma and tissue samples, and the pharmacokinetics and tissue distribution as
      well as the bioavailability of MCPT after i.g. were also illustrated. The results
      showed that MCPT could be highly converted to its active metabolite HCPT in
      plasma with the AUC0-infinity value of (185.28+/-61.73) ngh/mL and (717.25+/
      165.67) ngh/mL for MCPT and HCPT, respectively. Meanwhile, MCPT and HCPT were
      rapidly absorbed and diffused into all the tested tissues (heart, liver, spleen,
      lung, kidney and brain) after i.g. administration. Similar with the results after
      i.v. administration of MCPT, MCPT concentration in lung tissue was also extremely
      higher than in other tested tissues, which implied that MCPT might have a great
      potential for the treatment of lung cancer.

PMID- 29197299
TI  - Isotope-dilution gas chromatography-mass spectrometry coupled with injection-port
      butylation for the determination of 4-t-octylphenol, 4-nonylphenols and bisphenol
      A in human urine.
AB  - An analytical method that utilizes isotope-dilution gas chromatography-mass
      spectrometry (ID-GC-MS) coupled with injection-port butylation was developed. The
      method was validated, and confirmed to be able to determine the presence of three
      commonly detected endocrine-disrupting chemicals (EDCs: 4-tert-octylphenol (4-t
      OP), 4-nonylphenols (4-NPs) and bisphenol A (BPA)) in human urine with high
      precision and accuracy. After sample preparation by solid-phase extraction, the
      extract was introduced into GC-MS via injection-port butylation. The butylated
      target analytes were identified and quantified by using ion-trap mass
      spectrometry operating in the selected-ion-storage mode, and employing the
      measurement of peak area ratios of the butylated target analytes and labeled
      analogues in the samples and calibration standards. The labeled-analogues were
      also used to correct the variations associated with the analysis and matrix
      effect. The limits of quantitation (LOQs) ranged from 0.1 to 0.3ng/mL. High
      precisions for both intra- and inter-day analysis ranged from 1 to 6%, and
      excellent accuracy (mean recovery) ranged from 92 to 105% on two concentration
      levels. In human urine, the total concentrations of three selected EDCs varied
      from 1.28 to 7.14ng/mL. 4-NPs were detected within all collected samples. The
      developed method allows accurate analysis of trace-level of EDCs in urine, and
      these target EDCs could act as useful biomarkers to assess exposure in
      biomonitoring studies and programs.

PMID- 29197300
TI  - GC-MS method for determination and pharmacokinetic study of seven volatile
      constituents in rat plasma after oral administration of the essential oil of
      Rhizoma Curcumae.
AB  - Rhizoma Curcumae (RC) is perennial herbaceous plant mainly present in China,
      India and Malaysiabelong, which is belong to the family Zingiberaceae. The
      rhizomes of RC have been used as a famous traditional Chinese medicine for the
      treatment of syndrome of blood stasis. A selective, sensitive and accurate gas
      chromatography-mass spectroscopy (GC-MS) method was developed and validated in
      this paper for the simultaneous determination and pharmacokinetic study of alpha
      Pinene, 1,8-Cineole, Borneol, beta-Elemene, Curcumol, Germacrone, and Curdione in
      rat plasma. The GC-MS system was operated under selected ion monitoring (SIM)
      mode using a DB-5 (30m*0.25mm (ID)*0.25MUm (film thickness)) column. Linearity,
      intra-day and inter-day precisions, accuracy, extraction recovery and stability
      were used to validate the current GC/MS assay. The lowest limit of
      quantifications (LLOQ) of alpha-Pinene, 1,8-Cineole, Borneol, beta-Elemene,
      Curcumol, Germacrone, Curdione were 2.71ng/mL, 7.76ng/mL, 3.37ng/mL, 21.68ng/mL,
      40.21ng/mL, 24.84ng/mL and 47.78ng/mL respectively. After oral administration
      1.0g/kg of RC rhizomes to the rats, the maximum plasma concentration (Cmax) was
      34.72+/-9.97ng/mL for alpha-Pinene, 99.86+/-5.54ng/mL for 1,8-Cineole, 16.10+/
      3.37ng/mL for Borneol, 248.98+/-86.19ng/mL for beta-Elemene, 673.75+/-104.15ng/mL
      for Curcumol, 2353.64+/-637.83ng/mL for Germacrone and 2420.04+/-708.51ng/mL for
      Curdione. The time to reach the maximum plasma concentration (Tmax) was 2.33+/
      0.29h for alpha-Pinene, 0.67+/-0.29h for 1,8-Cineole, 1.33+/-0.58h for Borneol,
      1.83+/-0.76h for beta-Elemene, 0.83+/-0.29h for Curcumol, 0.89+/-0.98h for
      Germacrone and 1.17+/-0.76h for Curdione. In this study, a validated GC-MS method
      for simultaneous determination of seven volatile oil compounds in rat plasma
      after oral administration of the extract of RC rhizomes and research on their
      pharmacokinetics was validated. The recovery and stability results were
      satisfactory in this study.

PMID- 29197301
TI  - Dispensing-based bioprinting of mechanically-functional hybrid scaffolds with
      vessel-like channels for tissue engineering applications - A brief review.
AB  - Over the past decades, significant progress has been achieved in the field of
      tissue engineering (TE) to restore/repair damaged tissues or organs and, in this
      regard, scaffolds made from biomaterials have played a critical role. Notably,
      recent advances in biomaterials and three-dimensional (3D) printing have enabled
      the manipulation of two or more biomaterials of distinct, yet complementary,
      mechanical and/or biological properties to form so-called hybrid scaffolds
      mimicking native tissues. Among various biomaterials, hydrogels synthesized to
      incorporate living cells and/or biological molecules have dominated due to their
      hydrated tissue-like environment. Moreover, dispensing-based bioprinting has
      evolved to the point that it can now be used to create hybrid scaffolds with
      complex structures. However, the complexities associated with multi-material
      bioprinting and synthesis of hydrogels used for hybrid scaffolds pose many
      challenges for their fabrication. This paper presents a brief review of
      dispensing-based bioprinting of hybrid scaffolds for TE applications. The focus
      is on the design and fabrication of hybrid scaffolds, including imaging
      techniques, potential biomaterials, physical architecture, mechanical properties,
      cell viability, and the importance of vessel-like channels. The key issues and
      challenges for dispensing-based bioprinting of hybrid scaffolds are also
      identified and discussed along with recommendations for future research
      directions. Addressing these issues will significantly enhance the design and
      fabrication of hybrid scaffolds to and pave the way for translating them into
      clinical applications.

PMID- 29197302
TI  - The effect of impact duration on the axial fracture tolerance of the isolated
      tibia during automotive and military impacts.
AB  - Axial impacts to the lower leg during debilitating events such as frontal
      automotive collisions and military underbody blasts can cause significant
      injuries to the tibia. Several studies have conducted axial impact tests to
      determine the injury limits of the lower leg, mostly focused on automotive
      intrusions, resulting in an established force criterion for injury assessments.
      Due to the viscoelastic properties of bone, it remains unclear whether results
      from automotive experiments can be applied to higher-rate military blasts. Twelve
      male isolated cadaveric tibias (from six pairs, mean age: 62 +/- 8 years) were
      subjected to axial impact loads using a custom-built pneumatic impactor, with one
      specimen from each pair tested at velocity and impact durations representative of
      a military blast condition, and the contralateral under conditions representing
      an automotive collision. Impacts were applied in increasing levels of intensity
      (defined using energy levels) until fracture occurred. Fracture risk was
      influenced by projectile velocity, kinetic energy, impulse, and load rate, and
      there was a significant difference in peak force (p = 0.023), impulse (p = 0.09),
      and load rate (p = 0.025) between the automotive and military test conditions
      causing fracture. A 10% risk of fracture corresponded to an impact force of 9.0kN
      for the automotive condition and 12.2kN for the military condition. These results
      suggest that fracture tolerances developed in studies that simulate automotive
      impacts cannot be directly applied to military impacts of shorter duration. The
      number of factors identified to predict injury also suggests that fracture is not
      controlled by a single variable.

PMID- 29197303
TI  - Identification and structural elucidation of a new sildenafil analogue,
      dithiopropylcarbodenafil, from a premixed powder intended as a dietary
      supplement.
AB  - A new sildenafil analogue was detected during the monitoring of a premixed powder
      intended as a dietary supplement. The ultraviolet (UV) spectrum of the unknown
      compound was similar to that of dithiodesmethylcarbodenafil and
      dithiodesethylcarbodenafil, although their corresponding HPLC peaks were observed
      at different retention times. The chemical structure of the unknown compound was
      characterized by liquid chromatography-quadrupole-time-of-flight mass
      spectrometry (LC-Q-TOF/MS), followed by nuclear magnetic resonance (NMR) and
      infrared (IR) spectroscopy. The comparison of its structure with that of
      dithiodesmethylcarbodenafil, revealed that the N-methyl group on the piperazine
      ring is replaced by a propyl group. This new sildenafil analogue was identified
      as 5-(2-ethoxy-5-(4-propylpiperazine-1-carbonothioyl)phenyl)-1-methyl-3-propyl
      1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-thione and designated as a
      dithiopropylcarbodenafil. To the best of our knowledge, this is the first study
      reporting the identification and characterization of dithiopropylcarbodenafil.

PMID- 29197304
TI  - Determining the end of a musical turn: Effects of tonal cues.
AB  - Successful duetting requires that musicians coordinate their performance with
      their partners. In the case of turn-taking in improvised performance they need to
      be able to predict their partner's turn-end in order to accurately time their own
      entries. Here we investigate the cues used for accurate turn-end prediction in
      musical improvisations, focusing on the role of tonal structure. In a response
      time task, participants more accurately determined the endings of (tonal) jazz
      than (non-tonal) free improvisation turns. Moreover, for the jazz improvisations,
      removing low frequency information (<2100Hz) - and hence obscuring the pitch
      relationships conveying tonality - reduced response accuracy, but removing high
      frequency information (>2100Hz) had no effect. Neither form of filtering affected
      response accuracy in the free improvisation condition. We therefore argue that
      tonal cues aided prediction accuracy for the jazz improvisations compared to the
      free improvisations. We compare our results with those from related speech
      research (De Ruiter et al., 2006), to draw comparisons between the structural
      function of tonality and linguistic syntax.

PMID- 29197305
TI  - Internal Medicine Hospitalists' Perceived Barriers and Recommendations for
      Optimizing Secondary Prevention of Osteoporotic Hip Fractures.
AB  - OBJECTIVES: Osteoporosis is a major public health concern affecting an estimated
      10 million people in the United States. To the best of our knowledge, no
      qualitative study has explored barriers perceived by medicine hospitalists to
      secondary prevention of osteoporotic hip fractures. We aimed to describe these
      perceived barriers and recommendations regarding how to optimize secondary
      prevention of osteoporotic hip fracture. METHODS: In-depth, semistructured
      interviews were performed with 15 internal medicine hospitalists in a tertiary
      care referral medical center. The interviews were analyzed with directed content
      analysis. RESULTS: Internal medicine hospitalists consider secondary osteoporotic
      hip fracture prevention as the responsibility of outpatient physicians.
      Identified barriers were stratified based on themes including physicians'
      perception, patients' characteristics, risks and benefits of osteoporosis
      treatment, healthcare delivery system, and patient care transition from the
      inpatient to the outpatient setting. Some of the recommendations include building
      an integrated system that involves a multidisciplinary team such as the fracture
      liaison service, initiating a change to the hospital policy to facilitate
      inpatient care and management of osteoporosis, and creating a smooth patient care
      transition to the outpatient setting. CONCLUSIONS: Our study highlighted how
      internal medicine hospitalists perceive their role in the secondary prevention of
      osteoporotic hip fractures and what they perceive as barriers to initiating
      preventive measures in the hospital. Inconsistency in patient care transition and
      the fragmented nature of the existing healthcare system were identified as major
      barriers. A fracture liaison service could remove some of these barriers.

PMID- 29197306
TI  - Commentary on "Internal Medicine Hospitalists' Perceived Barriers and
      Recommendations for Optimizing Secondary Prevention of Osteoporotic Hip
      Fractures".

PMID- 29197307
TI  - Reducing the Time Spent Writing Notes Could Help Solve the Physician Shortage.

PMID- 29197308
TI  - Dramatic Reduction in 30-Day Readmissions Through High-Risk Screening and Two
      Phase Interdisciplinary Care.
AB  - OBJECTIVES: Thirty-day readmissions are common, serious, and costly. Most
      important, often they are preventable. The purpose of this quality improvement
      study was to evaluate an interdisciplinary, two-phase intervention to reduce 30
      day readmissions among high-risk medical patients. One or two high-risk patients
      were selected each weekday by a hospitalist using literature-based, locally
      tested criteria that included common medical illnesses, active psychiatric
      illness, and recent or recurrent hospital admissions. METHODS: Patients admitted
      to 1 of 5 medical hospitalist teams were selected to receive the intervention;
      patients admitted to the 4 remaining teams were used for comparison. The two
      phase care coordination intervention consisted of a daily interdisciplinary team
      meeting for the selected high-risk patients and postdischarge interventions that
      included outpatient care coordination until the patients' first follow-up
      appointment. The care plan addressed medical/geriatric assessment, social
      stability, medication reconciliation, nutritional needs, care coordination
      including future appointments/testing, and community services. Eighty-five
      patients in the intervention group were compared with 84 patients from the
      comparison group using propensity score matching. Patient characteristics were
      similar at baseline. RESULTS: The intervention group demonstrated a reduction in
      30-day readmissions by 52% (11 vs 23, P = 0.019). Length of stay was reduced: 5.5
      days compared with 7.2 days (P = 0.258). CONCLUSIONS: This intervention produced
      a significant reduction in 30-day readmissions for high-risk patients and a trend
      for shorter lengths of stay compared with similarly matched patients. Future
      research trials are needed to verify these results.

PMID- 29197309
TI  - Objective Structured Clinical Examination-Based Teaching of the Musculoskeletal
      Examination.
AB  - OBJECTIVES: Musculoskeletal complaints are the most common presenting illnesses
      in primary care settings, yet physicians often are underprepared to manage such
      complaints. We sought to create and evaluate an objective structured clinical
      examination (OSCE)-based musculoskeletal workshop designed to simultaneously
      educate medical students and internal medicine residents, enlisting volunteer
      medical students as standardized patients (SPs). METHODS: The setting for the
      study was the Yale Primary Care Residency Program. A comprehensive OSCE-based
      musculoskeletal workshop series was created, consisting of standalone workshops
      with evidence-based interactive lectures followed by OSCE stations. At each
      station, residents are evaluated on physical examination skills, differential
      diagnosis, and therapeutic plan. We assessed the impact of exposure to the
      neck/back pain workshop using written knowledge and clinical skills tests
      (maximum score 32) among both residents and medical students 6 months after
      exposure. RESULTS: A convenience sample of 13 residents exposed to the neck/back
      pain workshop was compared with 17 unexposed residents. Six months after exposure
      to the workshop, exposed residents, compared with unexposed residents, performed
      significantly better on a written knowledge test (score 8.6 vs 6.8, P = 0.005)
      and the clinical skills test (score 20.9 vs 17.1, P = 0.007). Similarly, medical
      student SPs performed significantly better on the clinical skills test (17.0 vs
      12.0, P = 0.02), compared with the control students. CONCLUSIONS: Our novel OSCE
      based musculoskeletal workshop, which enlists medical students to serve as SPs,
      engendered sustainable improvements in knowledge and clinical skills among both
      residents and participating students, thereby offering an innovative approach to
      simultaneously meeting both undergraduate and graduate medical education needs.

PMID- 29197310
TI  - Defining Medical Student Patient Care Responsibilities Before Intern Year:
      Results of a National Survey.
AB  - OBJECTIVES: Program directors have noted that first-year residents struggle with
      many of the patient care responsibilities they assume as they enter the US
      graduate medical education system. A national description of medical students'
      patient care experience in advance of graduation has not been published. We
      sought to describe the experience of US medical students during their clinical
      training by surveying the student representatives of each school. METHODS: We
      developed a mixed-methods survey that was delivered to representatives of 82
      schools via an e-mail link to an online survey. RESULTS: Our response rate was
      54% (44/82). Of those responding, 28% reported that students do not write any
      patient care orders at their institution and 34% reported not receiving pages
      related to patient care. Only 26% of institutions provide an increased patient
      load to students during their final year of training. Students identified many
      areas to improve the role of fourth-year medical students, including writing
      patient care orders, answering pages, increasing autonomy, defining their role
      better, and providing them with a longer subinternship experience. CONCLUSIONS:
      Our survey suggests that students are graduating from the undergraduate medical
      education system and moving to the graduate medical education system in the
      United States without a guarantee of having answered a page related to patient
      care or having placed a patient care order. Further studies of students'
      experiences should be conducted to explore whether exposure to these skills
      improves first-year resident performance.

PMID- 29197311
TI  - Radiologists' Recommendations for Additional Imaging on Inpatient CT Studies: Do
      Referring Physicians Follow Them?
AB  - OBJECTIVES: Studies have found that recommendations for additional imaging (RAI)
      accompany up to 31% of index computed tomography (CT) scans. In this study we
      assessed the frequency with which recommendations are accepted by the referring
      physician and the impact of AI on case management. METHODS: We performed a cross
      sectional study of all index CT scans of the chest, abdomen, and pelvis performed
      on adult inpatients during a 1-month period at a tertiary medical center. Each
      radiology report was examined for mention of RAI. We used a standardized
      abstraction tool to review medical records for the indication for the RAI
      (related to original diagnosis vs incidental finding), the clinician's rationale
      for pursuing or discarding the RAI, and the impact of the AI on the inpatient
      treatment plan. RESULTS: Among the 430 scans reviewed, most (57.7%) were of the
      abdomen/pelvis. RAI was recommended in 67 cases (odds ratio [OR] 15.6%; 95%
      confidence interval [CI] 12.4-19.3) and AI was completed in 24 of 67 cases
      (35.8%). Factors associated with a recommendation for AI were the presence of an
      incidental finding (OR 3.5, 95% CI 1.7-6.8) and verbal communication of the
      result to the ordering provider (OR 2.09, 95% CI 1.23-3.5). When performed, AI
      altered the treatment plan 75% (18/24) of the time. Among the 43 cases in which
      AI was not performed, 34.1% were deferred to outpatient, 13.6% underwent
      alternative clinical intervention, and 13.6% were judged unnecessary by the
      primary team. No rationale was documented in the chart for the remaining 38.6%.
      CONCLUSIONS: Despite concerns about autoreferral by radiologists for AI studies,
      we found a lower rate than in many prior studies, which may reflect a change in
      clinical practice. One-third of these recommendations were implemented and verbal
      communication was strongly associated with the likelihood of second image
      ordering. In the majority of the cases, the AI affected patient management. Based
      on these findings, radiologists should consider calling the ordering provider to
      increase the likelihood that the primary team will follow their recommendations.

PMID- 29197312
TI  - Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian
      Versus Non-Appalachian Populations of Kentucky.
AB  - OBJECTIVES: The aim of this study was to investigate whether patients with lung
      cancer in Appalachian Kentucky are more likely to develop multiple primary
      cancers than patients in non-Appalachian Kentucky. Additional analyses were
      conducted to identify other factors that may be associated with an increased
      hazard of developing multiple primary cancers in patients with lung cancer.
      METHODS: The data for this retrospective, population-based cohort study of 26,456
      primary lung cancer patients were drawn from the Kentucky Cancer Registry. For
      inclusion in the study, patients must have been diagnosed between January 1, 2000
      and December 31, 2013 and they must either have continually resided in
      Appalachian Kentucky or continually resided in non-Appalachian Kentucky. Cases
      were excluded if the patient was diagnosed as having additional primary cancers
      within 3 months of the initial diagnosis of primary lung cancer. The medical
      records for each case were examined to determine whether the patient was
      subsequently diagnosed as having additional primary cancers. The Cox proportional
      hazards model was then used to assess whether there was an association between
      the region in which the patients live and the likelihood of developing multiple
      primary cancers. Time to event was considered as the time from diagnosis to
      either death or development of a second primary cancer. RESULTS: The results
      presented here indicate that the risk of developing multiple primary cancers is
      the same for patients with lung cancer throughout Kentucky (hazard ratio [HR]
      1.002, P = 0.9713). We found no evidence for a greater hazard in patients from
      Appalachia; however, additional analyses revealed several high-risk groups. Male
      patients and older patients had a significantly greater hazard of developing
      multiple primary cancers (HR 1.169, P = 0.012 and 1.015, P = 0.0001,
      respectively). In addition, patients who underwent surgery and those who were
      diagnosed initially as having an earlier stage of cancer also were more likely to
      develop multiple primary cancers (HR 1.446, P = 0.0003 and 0.684, P = 0.0015,
      respectively). CONCLUSIONS: This is a negative study. Patients with primary lung
      cancer living in Appalachian Kentucky are not at a greater risk of developing
      multiple primary cancers than those residing in non-Appalachian Kentucky. High
      risk groups identified in this study are male patients and older patients. The
      increased hazard seen in patients who underwent surgery or those who were
      diagnosed as having earlier stages of lung cancer are likely an artifact of these
      patients living longer and, therefore, having more time to develop additional
      primary cancers.

PMID- 29197313
TI  - Variation in Use of Prophylactic Antibiotics in Gynecologic Procedures Before and
      After an Educational Intervention.
AB  - OBJECTIVES: Guidelines for use of prophylactic antibiotics in gynecologic
      procedures are outlined by the American Congress of Obstetricians and
      Gynecologists. There remains, however, a high rate of unindicated administration
      of antibiotics for surgeries. A retrospective study performed at our institution
      in 2012-2013 demonstrated that unindicated prophylactic antibiotics were
      administered over half the time. This study aimed to examine variations in the
      use of prophylactic antibiotics in patients undergoing gynecologic surgery at
      Scott and White Memorial Hospital and determine whether an educational
      intervention to gynecology physicians was associated with a significant decrease
      in unindicated prophylactic antibiotics. METHODS: A retrospective chart review
      was performed for all women undergoing gynecologic surgery at Scott and White
      Memorial Hospital in Temple, Texas for 1 year. An educational intervention
      regarding prophylactic antibiotic usage was held for obstetricians and
      gynecologists in the middle of that year. Subjects were included if they had
      procedures with a Current Procedural Terminology code corresponding to a
      procedure that does not require prophylactic antibiotics. Subjects were excluded
      if they had concurrent procedures for which antibiotics are recommended. RESULTS:
      A total of 500 subjects met inclusion and exclusion criteria, with 243 before the
      educational intervention and 257 after the intervention. In our study, a
      significant decrease (P < 0.0001) in unindicated prophylactic antibiotic use was
      demonstrated: from 45.7% (111/243) preintervention to 24.9% (64/257)
      postintervention. Before the educational intervention, both the gynecology
      oncology and reproductive endocrinology and infertility divisions had the highest
      rates of unindicated antibiotic use-91.7% (44/48) and 91.7% (33/36),
      respectively. The generalist and urogynecology divisions had the lowest rates for
      specialists before the intervention: 20.6% (30/146) and 30.8% (4/13),
      respectively. After the intervention, all of the divisions demonstrated an
      improvement in their rates of unindicated prophylactic antibiotic use. The
      urogynecology division demonstrated an improvement that can be considered
      clinically significant while not meeting statistical significance. The adverse
      event rates were not different between subjects who received preoperative
      prophylactic antibiotics (2.9%) and subjects who did not (2.8%). CONCLUSIONS: A
      simple educational intervention was associated with a significant decrease in
      unindicated prophylactic antibiotics in gynecologic procedures.

PMID- 29197315
TI  - Commentary on "Improving Postoperative Efficiency: An Algorithm for Expedited
      Void Trials After Urogynecologic Surgery".

PMID- 29197314
TI  - Improving Postoperative Efficiency: An Algorithm for Expedited Void Trials After
      Urogynecologic Surgery.
AB  - OBJECTIVES: To evaluate the relation between voided volume and void trial
      "success" to create an algorithm that minimizes the need for postvoid residual
      volume (PVR) assessment in backfill-assisted void trials. METHODS: This article
      is an ancillary analysis of deidentified data from a randomized trial evaluating
      prophylactic antibiotics after urogynecologic surgery. Void trials were routinely
      performed after surgery; voided volumes, PVR, and void trial outcomes were
      collected. The void trial regimen was as follows: the bladder was backfilled with
      300 mL of normal saline or until the patient reported the urgency to void, the
      catheter was removed, and the participant was prompted to void immediately. PVR
      volume was measured either by sonographic bladder scan or catheterization. Voided
      volumes were categorized in 25-mL increments from 50 to 225 mL. For each voided
      volume range, the PVR and void trial outcome data were incorporated to calculate
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) in terms of ability of voided volume alone to predict a
      passing void trial result. An algorithm was created using the voided volumes that
      optimize PPV and NPV. RESULTS: The study population included 255 participants.
      Voided volumes <100 mL and >=200 mL were identified as optimal thresholds to
      predict failure and passage of backfill-assisted void trials, respectively. When
      patients voided <100 mL, 3% passed their void trial (NPV odds ratio 96.7, 95%
      confidence interval 88.6-99.5). When patients voided >=200 mL, 97% passed (PPV
      odds ratio 97.4, 95% confidence interval 93.5-99.3). CONCLUSIONS: We propose an
      algorithm for void trials after urogynecologic surgery. After backfilling the
      bladder if voided volume is >=200 mL, the void trial is successful and no PVR is
      needed; if voided volume is between 100 and 199 mL, the void trial is
      indeterminate and PVR is recommended; and if voided volume is <100 mL, the void
      trial is unsuccessful and catheterization is needed. Applying this algorithm to
      our study population would have eliminated the need for PVR in 85% of patients.
      Calculated PPVs and NPVs depend on the prevalence of voiding dysfunction in the
      population being studied, and therefore may be unique to our institution.

PMID- 29197316
TI  - Developing a Mass Casualty Surge Capacity Protocol for Emergency Medical Services
      to Use for Patient Distribution.
AB  - OBJECTIVES: Metropolitan areas must be prepared to manage large numbers of
      casualties related to a major incident. Most US cities do not have adequate
      trauma center capacity to manage large-scale mass casualty incidents (MCIs).
      Creating surge capacity requires the distribution of casualties to hospitals that
      are not designated as trauma centers. Our objectives were to extrapolate MCI
      response research into operational objectives for MCI distribution plan
      development; formulate a patient distribution model based on research, hospital
      capacities, and resource availability; and design and disseminate a casualty
      distribution tool for use by emergency medical services (EMS) personnel to
      distribute patients to the appropriate level of care. METHODS: Working with
      hospitals within the region, we refined emergency department surge capacity for
      MCIs and developed a prepopulated tool for EMS providers to use to distribute
      higher-acuity casualties to trauma centers and lower-acuity casualties to
      nontrauma hospitals. A mechanism to remove a hospital from the list of available
      resources, if it is overwhelmed with patients who self-transport to the location,
      also was put into place. RESULTS: The number of critically injured survivors from
      an MCI has proven to be consistent, averaging 7% to 10%. Moving critically
      injured patients to level 1 trauma centers can result in a 25% reduction in
      mortality, when compared with care at nontrauma hospitals. US cities face major
      gaps in the surge capacity needed to manage an MCI. Sixty percent of "walking
      wounded" casualties self-transport to the closest hospital(s) to the incident.
      CONCLUSIONS: Directing critically ill patients to designated trauma centers has
      the potential to reduce mortality associated with the event. When applied to MCI
      responses, damage-control principles reduce resource utilization and optimize
      surge capacity. A universal system for mass casualty triage was identified and
      incorporated into the region's EMS. Flagship regional coordinating hospitals were
      designated to coordinate the logistics of the disaster response of both trauma
      designated and undesignated hospitals. Finally, a distribution tool was created
      to direct the flow of critically injured patients to trauma centers and redirect
      patients with lesser injuries to centers without trauma designation. The tool was
      distributed to local EMS personnel and validated in a series of tabletop and
      functional drills. These efforts demonstrate that a regional response to MCIs can
      be implemented in metropolitan areas under-resourced for trauma care.

PMID- 29197317
TI  - Cross-Sectional Study of the Relation of Health Literacy to Primary Language and
      Emergency Department Length of Stay.
AB  - OBJECTIVES: The primary aim of this study was to determine whether emergency
      department (ED) length of stay (LOS) or primary language was related to the
      degree of health literacy of patients. METHODS: Adult English-speaking and
      Spanish-speaking patients were recruited for the study. Participants completed
      the Newest Vital Sign (NVS) tool (English and Spanish versions), a 6-question
      validated scale. Patients with NVS scores of 0 to 3 were considered to be at risk
      for limited health literacy, whereas those with adequate health literacy were
      defined as scoring a 4 to 6. After completion of their ED visit, a retrospective
      chart review was performed to identify the patient's ED LOS (time from
      registration to time of disposition) and ED disposition. In addition, 2 single
      item questions were compared with the NVS for validity. RESULTS: Participants
      included 250 English-speaking and 257 Spanish-speaking subjects. Per the NVS, 71%
      (359 of 507) of all patients had limited health literacy. By language group,
      significantly more Spanish-speaking than English-speaking patients had limited
      health literacy (93% vs 48%, diff 45%, 95% confidence interval 37-51). There was
      no significant difference in LOS between the limited health literacy group and
      adequate health literacy group (medians 440 vs 461 min). The 2 single-item
      questions had fair validity in comparison to the NVS scale (kappa 0.2-0.3).
      CONCLUSIONS: There was a significant difference in health literacy based on
      language, with 93% of all Spanish-speaking patients in our sample having limited
      health literacy. We found no significant difference in ED LOS between patients
      with limited health and adequate health literacy in an academic urban ED setting.

PMID- 29197318
TI  - Erratum: EMS Patients and Walk-In Patients Presenting With Severe Sepsis:
      Differences in Management and Outcome: Erratum.

PMID- 29197319
TI  - Editorial: Multi-target Drug Discovery - Part II.

PMID- 29197320
TI  - ERRATUM: SAMHD1 Polymorphisms were Significantly Correlated with HIV/SIV Virus
      Load in PBMC from Chinese Rhesus Macaques and Cynomolgus Macaques

PMID- 29197321
TI  - Preface.

PMID- 29197322
TI  - Editorial: Futuristic Protein Engineering: Developments and Avenues.

PMID- 29197323
TI  - Alignment-free comparative genomic screen for structured RNAs using coarse
      grained secondary structure dot plots.
AB  - BACKGROUND: Structured non-coding RNAs play many different roles in the cells,
      but the annotation of these RNAs is lacking even within the human genome. The
      currently available computational tools are either too computationally heavy for
      use in full genomic screens or rely on pre-aligned sequences. METHODS: Here we
      present a fast and efficient method, DotcodeR, for detecting structurally similar
      RNAs in genomic sequences by comparing their corresponding coarse-grained
      secondary structure dot plots at string level. This allows us to perform an all
      against-all scan of all window pairs from two genomes without alignment. RESULTS:
      Our computational experiments with simulated data and real chromosomes
      demonstrate that the presented method has good sensitivity. CONCLUSIONS: DotcodeR
      can be useful as a pre-filter in a genomic comparative scan for structured RNAs.

PMID- 29197325
TI  - Genomic prediction accuracies in space and time for height and wood density of
      Douglas-fir using exome capture as the genotyping platform.
AB  - BACKGROUND: Genomic selection (GS) can offer unprecedented gains, in terms of
      cost efficiency and generation turnover, to forest tree selective breeding;
      especially for late expressing and low heritability traits. Here, we used: 1)
      exome capture as a genotyping platform for 1372 Douglas-fir trees representing 37
      full-sib families growing on three sites in British Columbia, Canada and 2)
      height growth and wood density (EBVs), and deregressed estimated breeding values
      (DEBVs) as phenotypes. Representing models with (EBVs) and without (DEBVs)
      pedigree structure. Ridge regression best linear unbiased predictor (RR-BLUP) and
      generalized ridge regression (GRR) were used to assess their predictive
      accuracies over space (within site, cross-sites, multi-site, and multi-site to
      single site) and time (age-age/ trait-trait). RESULTS: The RR-BLUP and GRR models
      produced similar predictive accuracies across the studied traits. Within-site GS
      prediction accuracies with models trained on EBVs were high (RR-BLUP: 0.79-0.91
      and GRR: 0.80-0.91), and were generally similar to the multi-site (RR-BLUP: 0.83
      0.91, GRR: 0.83-0.91) and multi-site to single-site predictive accuracies (RR
      BLUP: 0.79-0.92, GRR: 0.79-0.92). Cross-site predictions were surprisingly high,
      with predictive accuracies within a similar range (RR-BLUP: 0.79-0.92, GRR: 0.78
      0.91). Height at 12 years was deemed the earliest acceptable age at which
      accurate predictions can be made concerning future height (age-age) and wood
      density (trait-trait). Using DEBVs reduced the accuracies of all cross-validation
      procedures dramatically, indicating that the models were tracking pedigree
      (family means), rather than marker-QTL LD. CONCLUSIONS: While GS models'
      prediction accuracies were high, the main driving force was the pedigree tracking
      rather than LD. It is likely that many more markers are needed to increase the
      chance of capturing the LD between causal genes and markers.

PMID- 29197324
TI  - Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B
      action in hippocampus.
AB  - BACKGROUND: PDE4 cyclic nucleotide phosphodiesterases regulate 3', 5' cAMP
      abundance in the CNS and thereby regulate PKA activity and phosphorylation of
      CREB, which has been implicated in learning and memory, depression and other
      functions. The PDE4 isoform PDE4B1 also interacts with the DISC1 protein,
      implicated in neural development and behavioral disorders. The cellular functions
      of PDE4B1 have been investigated extensively, but its function(s) in the intact
      organism remained unexplored. RESULTS: To specifically disrupt PDE4B1, we
      developed mice that express a PDE4B1-D564A transgene in the hippocampus and
      forebrain. The transgenic mice showed enhanced phosphorylation of CREB and ERK1/2
      in hippocampus. Hippocampal neurogenesis was increased in the transgenic mice.
      Hippocampal electrophysiological studies showed increased baseline synaptic
      transmission and enhanced LTP in male transgenic mice. Behaviorally, male
      transgenic mice showed increased activity in prolonged open field testing, but
      neither male nor female transgenic mice showed detectable anxiety-like behavior
      or antidepressant effects in the elevated plus-maze, tail-suspension or forced
      swim tests. Neither sex showed any significant differences in associative fear
      conditioning or showed any demonstrable abnormalities in pre-pulse inhibition.
      CONCLUSIONS: These data support the use of an isoform-selective approach to the
      study of PDE4B1 function in the CNS and suggest a probable role of PDE4B1 in
      synaptic plasticity and behavior. They also provide additional rationale and a
      refined approach to the development of small-molecule PDE4B1-selective
      inhibitors, which have potential functions in disorders of cognition, memory,
      mood and affect.

PMID- 29197326
TI  - Potentially inappropriate prescriptions for elderly people taking antidepressant:
      comparative tools.
AB  - BACKGROUND: The use of psychotropic drugs by elderly people is widely spread
      around the world, given that prevalence of inappropriate medication is frequent.
      Strictly speaking, in Brazil, the vulnerable population of elderly people is more
      likely to use Potentially Inappropriate Psychotropic (PIP) due to the impact of
      social-economic characteristics, to the Brazilian Public Health System, and to
      the lack of patient monitoring. However, neither the use pattern nor the
      prevalence rate of PIP have been studied in Brazil so far. The objectives of this
      study were to determine the prevalence of PIP in elderly outpatients taking
      antidepressants, and to compare the performance of two different tools (Beers,
      STOPP). METHODS: This cross-sectional study involved all the aged outpatients (>=
      60 years of age) taking antidepressants attended by the public health system in a
      city of the State of Sao Paulo, Brazil. Data were obtained from a pharmacy
      database and medical records. All psychotropic drugs evaluated included:
      antidepressants, antipsychotics, anti-epileptics and benzodiazepines. STOPP and
      Beers criteria were applied to detect PIP. RESULTS: One thousand one hundred
      forty prescriptions from 174 outpatients were subjected to two different
      screening tools. The average patient age was 67 (interquartile range 63-74) and
      the median number of drugs used was 3.0 (interquartile 2-4) per patient. The
      overall prevalence of PIP was 121 (69.5%). The levels of PIP observed according
      to tools were 39.6% (STOPP) and 29.9% (Beers).The long-term use of
      benzodiazepines was the most common PIP recognized, and the one which contributed
      more significantly to higher levels of PIP than other medications. CONCLUSIONS:
      The prevalence of PIP was high among the elderly. STOPP criteria identified more
      PIP than Beers criteria. Knowledge of PIP prevalence should gear efforts to
      reduce the level of inappropriate prescriptions and may provide the need for
      developing national criteria.

PMID- 29197327
TI  - Re-evaluation of the Haarlem Archaeopteryx and the radiation of maniraptoran
      theropod dinosaurs.
AB  - BACKGROUND: Archaeopteryx is an iconic fossil that has long been pivotal for our
      understanding of the origin of birds. Remains of this important taxon have only
      been found in the Late Jurassic lithographic limestones of Bavaria, Germany.
      Twelve skeletal specimens are reported so far. Archaeopteryx was long the only
      pre-Cretaceous paravian theropod known, but recent discoveries from the
      Tiaojishan Formation, China, yielded a remarkable diversity of this clade,
      including the possibly oldest and most basal known clade of avialan, here named
      Anchiornithidae. However, Archaeopteryx remains the only Jurassic paravian
      theropod based on diagnostic material reported outside China. RESULTS: Re
      examination of the incomplete Haarlem Archaeopteryx specimen did not find any
      diagnostic features of this genus. In contrast, the specimen markedly differs in
      proportions from other Archaeopteryx specimens and shares two distinct characters
      with anchiornithids. Phylogenetic analysis confirms it as the first anchiornithid
      recorded outside the Tiaojushan Formation of China, for which the new generic
      name Ostromia is proposed here. CONCLUSIONS: In combination with a biogeographic
      analysis of coelurosaurian theropods and palaeogeographic and stratigraphic data,
      our results indicate an explosive radiation of maniraptoran coelurosaurs probably
      in isolation in eastern Asia in the late Middle Jurassic and a rapid, at least
      Laurasian dispersal of the different subclades in the Late Jurassic. Small body
      size and, possibly, a multiple origin of flight capabilities enhanced dispersal
      capabilities of paravian theropods and might thus have been crucial for their
      evolutionary success.

PMID- 29197328
TI  - Vaccine-derived poliovirus surveillance in China during 2001-2013: the potential
      challenge for maintaining polio free status.
AB  - BACKGROUND: The goal of polio eradication is to complete elimination and
      containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived
      poliovirus (VDPV) surveillance in China from 2001-2013 is summarized in this
      report, which has important implications for the global polio eradication
      initiative. METHODS: Acute flaccid paralysis (AFP) cases and their contacts with
      VDPVs isolated from fecal specimens were identified in our AFP surveillance
      system or by field investigation. Epidemiological and laboratory information for
      these children were analyzed and the reasons for the VDPV outbreak was explored.
      RESULTS: VDPVs were isolated from a total of 49 children in more than two-thirds
      of Chinese provinces from 2001-2013, including 15 VDPV cases, 15 non-polio AFP
      cases and 19 contacts of AFP cases or healthy subjects. A total of 3 circulating
      VDPVs (cVDPVs) outbreaks were reported in China, resulting in 6 cVDPVs cases who
      had not been vaccinated with oral attenuated poliomyelitis vaccine. Among the 4
      immunodeficiency-associated VDPVs (iVDPVs) cases, the longest duration of virus
      excretion was about 20 months. In addition, one imported VDPV case from Myanmar
      was detected in Yunnan Province. CONCLUSIONS: Until all wild, vaccine-related and
      Sabin polioviruses are eradicated in the world, high quality routine immunization
      and sensitive AFP surveillance should be maintained, focusing efforts on
      underserved populations in high risk areas.

PMID- 29197329
TI  - What does it mean when people say that they have received expressions of concern
      about their drinking or advice to cut down on the AUDIT scale?
AB  - BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) is a commonly
      used scale to measure severity of alcohol consumption that contains an item
      asking if anyone has expressed concern about your drinking or suggested you cut
      down. What does it mean when a participant says yes to this question? METHODS:
      Participants who were 18 or older and who drank at least weekly were recruited to
      complete a survey about their drinking from the Mechanical Turk platform.
      Comparisons were made between at risk (n = 2565) and high risk drinkers (n = 581)
      who said that someone had expressed concern about their drinking regarding who
      had expressed concern. If the person expressing concern was a health
      professional, the participant was also asked what type of support was provided.
      RESULTS: Expressions of concern about drinking were received more often by high
      risk than at risk drinkers. The most common type of person to have expressed
      concern was a relative, followed by a friend, or a marital partner. About one
      quarter of participants had received expressions of concern from a medical doctor
      or other health professional. All health professionals' expressions of concern
      were accompanied by a suggestion to cut down and about half provided some
      additional support (the most common type of support was brief advice).
      CONCLUSIONS: Expressions of concern come from a variety of sources and the
      likelihood of their occurrence is partially related to amount of alcohol intake.

PMID- 29197330
TI  - Chronic wounds alter the proteome profile in skin mucus of farmed gilthead
      seabream.
AB  - BACKGROUND: Skin and its mucus are known to be the first barrier of defence
      against any external stressors. In fish, skin wounds frequently appear as a
      result of intensive culture and also some diseases have skin ulcers as external
      clinical signs. However, there is no information about the changes produced by
      the wounds in the mucosae. In the present paper, we have studied the alterations
      in the proteome map of skin mucus of gilthead seabream during healing of
      experimentally produced chronic wounds by 2-DE followed by LC-MS/MS. The
      corresponding gene expression changes of some identified skin proteins were also
      investigated through qPCR. RESULTS: Our study has successfully identified 21
      differentially expressed proteins involved in immunity and stress processes as
      well as other metabolic and structural proteins and revealed, for the first time,
      that all are downregulated in the skin mucus of wounded seabream specimens. At
      transcript level, we found that four of nine markers (ighm, gst3, actb and krt1)
      were downregulated after causing the wounds while the rest of them remained
      unaltered in the wounded fish. Finally, ELISA analysis revealed that IgM levels
      were significantly lower in wounded fish compared to the control fish.
      CONCLUSIONS: Our study revealed a decreased-expression at protein and for some
      transcripts at mRNA levels in wounded fish, which could affect the functionality
      of these molecules, and therefore, delay the wound healing process and increase
      the susceptibility to any infection after wounds in the skin of gilthead
      seabream.

PMID- 29197331
TI  - Genotyping and drug susceptibility testing of mycobacterial isolates from
      population-based tuberculosis prevalence survey in Ghana.
AB  - BACKGROUND: Mycobacterium tuberculosis complex (MTBC) and Non-tuberculosis
      Mycobacterium (NTM) infections differ clinically, making rapid identification and
      drug susceptibility testing (DST) very critical for infection control and drug
      therapy. This study aims to use World Health Organization (WHO) approved line
      probe assay (LPA) to differentiate mycobacterial isolates obtained from
      tuberculosis (TB) prevalence survey in Ghana and to determine their drug
      resistance patterns. METHODS: A retrospective study was conducted whereby a total
      of 361 mycobacterial isolates were differentiated and their drug resistance
      patterns determined using GenoType Mycobacterium Assays: MTBC and CM/AS for
      differentiating MTBC and NTM as well MTBDRplus and NTM-DR for DST of MTBC and NTM
      respectively. RESULTS: Out of 361 isolates, 165 (45.7%) MTBC and 120 (33.2%) NTM
      (made up of 14 different species) were identified to the species levels whiles 76
      (21.1%) could not be completely identified. The MTBC comprised 161 (97.6%)
      Mycobacterium tuberculosis and 4 (2.4%) Mycobacterium africanum. Isoniazid and
      rifampicin monoresistant MTBC isolates were 18/165 (10.9%) and 2/165(1.2%)
      respectively whiles 11/165 (6.7%) were resistant to both drugs. Majority 42/120
      (35%) of NTM were M. fortuitum. DST of 28 M. avium complex and 8 M. abscessus
      complex species revealed that all were susceptible to macrolides (clarithromycin,
      azithromycin) and aminoglycosides (kanamycin, amikacin, and gentamicin).
      CONCLUSION: Our research signifies an important contribution to TB control in
      terms of knowledge of the types of mycobacterium species circulating and their
      drug resistance patterns in Ghana.

PMID- 29197332
TI  - RNA-seq-based genome annotation and identification of long-noncoding RNAs in the
      grapevine cultivar 'Riesling'.
AB  - BACKGROUND: The technological advances of RNA-seq and de novo transcriptome
      assembly have enabled genome annotation and transcriptome profiling in highly
      heterozygous species such as grapevine (Vitis vinifera L.). This work is an
      attempt to utilize a de novo-assembled transcriptome of the V. vinifera cultivar
      'Riesling' to improve annotation of the grapevine reference genome sequence.
      RESULTS: Here we show that the transcriptome assembly of a single V. vinifera
      cultivar is insufficient for a complete genome annotation of the grapevine
      reference genome constructed from V. vinifera PN40024. Further, we provide
      evidence that the gene models we identified cannot be completely anchored to the
      previously published V. vinifera PN40024 gene models. In addition to these
      findings, we present a computational pipeline for the de novo identification of
      lncRNAs. Our results demonstrate that, in grapevine, lncRNAs are significantly
      different from protein coding transcripts in such metrics as length, GC-content,
      minimum free energy, and length-corrected minimum free energy. CONCLUSIONS: In
      grapevine, high-level heterozygosity necessitates that transcriptome
      characterization be based on cultivar-specific reference genome sequences. Our
      results strengthen the hypothesis that lncRNAs have thermodynamically different
      properties than protein-coding RNAs. The analyses of both coding and non-coding
      RNAs will be instrumental in uncovering inter-cultivar variation in wild and
      cultivated grapevine species.

PMID- 29197333
TI  - Double product reflects the association of heart rate with MACEs in acute
      coronary syndrome patients treated with percutaneous coronary intervention.
AB  - BACKGROUND: There is little information about the prognostic value of double
      product (DP) for acute coronary syndrome (ACS) patients treated with percutaneous
      coronary intervention (PCI). The aim of this study was to investigate whether DP
      reflects the predictive power of heart rate (HR) or systolic blood pressure (SBP)
      in ACS patients treated with PCI. METHODS: A total of 7590 ACS patients who had
      undergone PCI, free from cardiac shock, were included. The follow-up duration was
      two years. The main adverse cardiovascular events (MACEs) included all-cause
      death, recurrent myocardial infarction and stroke. RESULTS: In the unadjusted
      model, significantly higher rates of MACEs were recorded in the high DP group
      (relative risk 1.41, 95%CI 1.08 to 1.83, p = 0.012). However, in the full
      adjusted models, after including HR and SBP, the predictive value of DP was not
      significant (relative risk 0.86, 95%CI 0.55 to1.33, p = 0.499). The predictive
      value of HR for MACEs was statistically significant (relative risk 1.74, 95% CI
      1.33-2.28, p < 0.001). It was worth noting that the history of hypertension was
      strongly associated with MACEs (relative risk 1.53, 95% CI 1.11-2.11, p = 0.009).
      CONCLUSION: High DP is associated with MACEs for ACS patients treated with PCI.
      However, the predictive value of DP weakened when adjusted for HR. Therefore, we
      have shown that DP may reflect the predictive power of HR for ACS patients
      treated with PCI.

PMID- 29197334
TI  - Identification and characterization of Prunus persica miRNAs in response to UVB
      radiation in greenhouse through high-throughput sequencing.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene
      expression of target mRNAs involved in plant growth, development, and abiotic
      stress. As one of the most important model plants, peach (Prunus persica) has
      high agricultural significance and nutritional values. It is well adapted to be
      cultivated in greenhouse in which some auxiliary conditions like temperature,
      humidity, and UVB etc. are needed to ensure the fruit quality. However, little is
      known about the genomic information of P. persica under UVB supplement.
      Transcriptome and expression profiling data for this species are therefore
      important resources to better understand the biological mechanism of seed
      development, formation and plant adaptation to environmental change. Using a high
      throughput miRNA sequencing, followed by qRT-PCR tests and physiological
      properties determination, we identified the responsive-miRNAs under low-dose UVB
      treatment and described the expression pattern and putative function of related
      miRNAs and target genes in chlorophyll and carbohydrate metabolism. RESULTS: A
      total of 164 known peach miRNAs belonging to 59 miRNA families and 109 putative
      novel miRNAs were identified. Some of these miRNAs were highly conserved in at
      least four other plant species. In total, 1794 and 1983 target genes for known
      and novel miRNAs were predicted, respectively. The differential expression
      profiles of miRNAs between the control and UVB-supplement group showed that UVB
      responsive miRNAs were mainly involved in carbohydrate metabolism and signal
      transduction. UVB supplement stimulated peach to synthesize more chlorophyll and
      sugars, which was verified by qRT-PCR tests of related target genes and
      metabolites' content measurement. CONCLUSION: The high-throughput sequencing data
      provided the most comprehensive miRNAs resource available for peach study. Our
      results identified a series of differentially expressed miRNAs/target genes that
      were predicted to be low-dose UVB-responsive. The correlation between
      transcriptional profiles and metabolites contents in UVB supplement groups gave
      novel clues for the regulatory mechanism of miRNAs in Prunus. Low-dose UVB
      supplement could increase the chlorophyll and sugar (sorbitol) contents via miRNA
      target genes and therefore improve the fruit quality in protected cultivation of
      peaches.

PMID- 29197335
TI  - Trends in prevalence, mortality, health care utilization and health care costs of
      Swiss IBD patients: a claims data based study of the years 2010, 2012 and 2014.
AB  - BACKGROUND: Real-life data on inflammatory bowel disease (IBD) prevalence and
      costs are scarce. The aims of this study were to provide an overview of the
      prevalence, mortality, health care utilization and costs of IBD patients in
      Switzerland in the years 2010, 2012, and 2014. METHODS: Based on claims data of
      the Helsana-Group, prevalence of IBD was assessed for 2010, 2012 and 2014.
      Mortality rates, costs (inpatient, outpatient, medication costs) and utilization
      (visits, hospitalizations) were compared between patients with and without IBD,
      and between IBD patients treated with and without biologics. Results were
      extrapolated to the Swiss general population using national census data.
      Multivariate linear regression was used to identify socio-demographic and
      regional factors influencing total costs. RESULTS: The overall extrapolated
      prevalence rates of IBD were 0.32% in 2010, 0.38% in 2012, and 0.41% in 2014.
      Mortality rate didn't differ between the IBD and non-IBD population. Costs
      increased annually by 6% in IBD versus 2.4% in non-IBD subjects, which was solely
      due to increased outpatient costs. Almost one-fourth of IBD patients were
      hospitalized at least once a year. Costs were higher in IBD patients treated with
      biologics (OR = 3.98, CI: 3.72-4.27, p < 0.001) when compared to IBD patients
      without biologic therapies. Over 70% of the total costs in IBD patients treated
      with biologics were due to drug costs, compared with 28% in patients without use
      of biologic therapies, whereas inpatient costs didn't differ. CONCLUSIONS: The
      prevalence of IBD seems to be increasing in Switzerland. Outpatient costs
      increased substantially, while no decrease in inpatient costs was found.
      Treatment of IBD is more and more based on biologic therapies.

PMID- 29197336
TI  - Contrasting patterns of evolutionary constraint and novelty revealed by
      comparative sperm proteomic analysis in Lepidoptera.
AB  - BACKGROUND: Rapid evolution is a hallmark of reproductive genetic systems and
      arises through the combined processes of sequence divergence, gene gain and loss,
      and changes in gene and protein expression. While studies aiming to disentangle
      the molecular ramifications of these processes are progressing, we still know
      little about the genetic basis of evolutionary transitions in reproductive
      systems. Here we conduct the first comparative analysis of sperm proteomes in
      Lepidoptera, a group that exhibits dichotomous spermatogenesis, in which males
      produce a functional fertilization-competent sperm (eupyrene) and an incompetent
      sperm morph lacking nuclear DNA (apyrene). Through the integrated application of
      evolutionary proteomics and genomics, we characterize the genomic patterns
      potentially associated with the origination and evolution of this unique
      spermatogenic process and assess the importance of genetic novelty in
      Lepidopteran sperm biology. RESULTS: Comparison of the newly characterized
      Monarch butterfly (Danaus plexippus) sperm proteome to those of the Carolina
      sphinx moth (Manduca sexta) and the fruit fly (Drosophila melanogaster)
      demonstrated conservation at the level of protein abundance and post
      translational modification within Lepidoptera. In contrast, comparative genomic
      analyses across insects reveals significant divergence at two levels that
      differentiate the genetic architecture of sperm in Lepidoptera from other
      insects. First, a significant reduction in orthology among Monarch sperm genes
      relative to the remainder of the genome in non-Lepidopteran insect species was
      observed. Second, a substantial number of sperm proteins were found to be
      specific to Lepidoptera, in that they lack detectable homology to the genomes of
      more distantly related insects. Lastly, the functional importance of Lepidoptera
      specific sperm proteins is broadly supported by their increased abundance
      relative to proteins conserved across insects. CONCLUSIONS: Our results identify
      a burst of genetic novelty amongst sperm proteins that may be associated with the
      origin of heteromorphic spermatogenesis in ancestral Lepidoptera and/or the
      subsequent evolution of this system. This pattern of genomic diversification is
      distinct from the remainder of the genome and thus suggests that this transition
      has had a marked impact on lepidopteran genome evolution. The identification of
      abundant sperm proteins unique to Lepidoptera, including proteins distinct
      between specific lineages, will accelerate future functional studies aiming to
      understand the developmental origin of dichotomous spermatogenesis and the
      functional diversification of the fertilization incompetent apyrene sperm morph.

PMID- 29197337
TI  - Genome-wide motif predictions of BCARR-box in the amino-acid repressed genes of
      Lactobacillus helveticus CM4.
AB  - BACKGROUND: A BCARR (branched-chain amino acid responsive repressor) identified
      in proteolytic gene expressions in Lactobacillus helveticus is considered to
      negatively control transcriptions by binding to operator sites at the promoter
      regions in the presence of BCAAs. However, the distributions and regulatory
      potential of the BCARR in all genes repressed by BCAAs in CM4 remains unclear.
      RESULTS: A genome-wide search for the BCARR-box was conducted to clarify the
      contribution of BCARR in the regulation of amino acid metabolism in L. helveticus
      CM4. Among all 2174 genes of CM4, 390 genes repressed by amino acids were
      selected for the search of the BCARR-box. The annotated 33 genes among the 67
      predicted BCARR-boxes were mainly linked to amino acid metabolism. The BCARR
      boxes were mainly located adjacent to the -35 sequence of the promoter; however,
      the repressive effects in different locations were similar. Notably, the
      consensus BCARR-box motif, 5'-A1A2A3A4A5W6N7N8N9W10T11T12W13T14T15-3', observed
      in highly repressed genes, revealed more frequent A-T base pairing and a lower
      free energy than that in lowly repressed genes. A MEME analysis also supported
      the lower frequency of T at positions 12, 14, 13 and 15 in the BCARR-box sequence
      of the lowly repressed gene group. These results reveal that genes with a more
      stable palindromic structure might be preferable targets for BCARR binding and
      result in higher repressions in the target gene expressions. CONCLUSIONS: Our
      genome-wide search revealed the involvement of the proteolytic system,
      transporter system and some transcriptional regulator systems in BCARR-box
      regulation in L. helveticus CM4.

PMID- 29197338
TI  - Dose-response studies of Ropivacaine in blood flow of upper extremity after
      supraclavicular block: a double-blind randomized controlled study.
AB  - BACKGROUND: The sympathetic block of upper limb leading to increased blood flow
      has important clinical implication in microvascular surgery. However, little is
      known regarding the relationship between concentration of local anesthetic and
      blood flow of upper limb. The aim of this dose-response study was to determine
      the ED50 and ED95 of ropivacaine in blood flow after supraclavicular block (SB).
      METHODS: Patients undergoing upper limb surgery and supraclavicular block were
      randomly assigned to receive 30ml ropivacaine in concentrations of 0.125%(A
      Group), 0.2%(B Group), 0.25%(C Group), 0.375%(D Group), 0.5%(E Group), or 0.75%(F
      Group) (n=13 per group). All patients received supraclavicular block (SB). Time
      average maximum velocity (TAMAX), cross-sectional area (CSA) of brachial artery
      and skin temperatures (Ts) were measured repeatedly at the same marked points,
      they were taken at baseline (before block, t0) and at 30min after SB (t1). Blood
      flow(BF) = TAMAX* CSA*60 sec.. Relative blood flow (DeltaBF) = BFt1/ BFt0.
      Success of SB was assessed simultaneously. Supplementary anesthesia and other
      adverse events (AE) were recorded. RESULTS: Significant increase in TAMAX, CSA,
      BF and Ts were seen in all concentration groups at t1 comparing with t0
      (P<0.001). There was an upward trend of TAMAX, CSA, BF with the increasing
      concentration of ropivacaine except Ts. There was no significant different of Ts
      at t1 among different concentration group. The dose-response formula of
      ropivacaine on DeltaBF was Y=1+3.188/(1+10^((-2.451-X) * 1.730)) and ED50/ED95
      (95%CI) were 0.35/1.94%(0.25-0.45/0.83-4.52), and R2 (coefficient of
      determination) =0.85. ED50/ED95 (95%CI) values of sensory block were 0.18/0.33%
      (0.15-0.21/0.27-0.51), R2=0.904. CONCLUSIONS: The dose-response curve between SB
      ropivacaine and the changes of BF was determined. The ED50/ED95 of ropivacaine of
      DeltaBF are 0.35/1.94% (0.25-0.45/0.83-4.52). TAMAX, CSA and BF consistently
      increased with ropivacaine concentration. The maximal sympathetic block needs
      higher concentration than that complete sensation block needs which may benefit
      for microvascular surgery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02139982 .
      Retrospectively registered (Date of registration: May, 2014).

PMID- 29197339
TI  - Irritable bowel syndrome: prevalence, risk factors in an adult Lebanese
      population.
AB  - BACKGROUND: Very few studies report on the prevalence of irritable bowel syndrome
      (IBS) and its correlates in the Middle East. This study investigated Irritable
      Bowel Syndrome (IBS) prevalence in a sample of Lebanese adult individuals and
      associated demographic and behavioral lifestyle factors. METHODS: This is an
      observational population-based study. The target population is working Lebanese
      adults, eighteen-to-sixty five years old. The sample was selected from a
      convenience population of bank employees in different geographical areas in
      Lebanon. The study participants completed an anonymous self-administered
      questionnaire, to collect data on their socio-demographic, behavioral and life
      style characteristics, and diagnostic questions following Rome III criteria to
      assess IBS occurrence. The difference in IBS prevalence by socio-demographic
      characteristics, smoking, alcohol consumption, and physical activity was assessed
      by using the Chi-square test. Logistic regression adjusted odds ratios were used
      to investigate the association between risk factors and IBS. RESULTS: Data was
      collected from 553 individuals and consisted of 52.8% females (mean age 35.9
      years, SD = 11.9) and 47.2% males (mean age = 36.1 years, SD = 10.3). The
      prevalence of IBS in the study population according to Rome III criteria was
      20.1%. The bivariate analysis indicated that being younger than 30 years old, a
      female, an ever water pipe smoker, an ever alcohol consumer are significantly
      associated with a higher prevalence of IBS. Educational level, cigarettes smoking
      and physical exercise were not significantly associated with IBS occurrence. The
      logistic regression adjusted odds ratio showed that females were 1.67 times more
      likely to have IBS than males (P? 0.05). The participants aged less than 30 years
      old were at a higher risk of having IBS (P? 0.01). Those who ever smoked
      waterpipe were 1.63 times more likely to have IBS than those who never smoked
      waterpipe (P? 0.05). Those who were ever alcohol drinkers were twice as likely to
      have IBS than never-drinkers (P? 0.01). CONCLUSION: New data on the high
      prevalence of IBS in an adult population in Lebanon has been reported. This is
      also the first study to investigate and show an association of waterpipe smoking
      and IBS. Further longitudinal studies are warranted to determine whether this
      association is causal.

PMID- 29197340
TI  - Clinical significance and risk factors for new onset and recurring atrial
      fibrillation following cardiac surgery - a retrospective data analysis.
AB  - BACKGROUND: Although mortality after cardiac surgery has significantly decreased
      in the last decade, patients still experience clinically relevant postoperative
      complications. Among others, atrial fibrillation (AF) is a common consequence of
      cardiac surgery, which is associated with prolonged hospitalization and increased
      mortality. METHODS: We retrospectively analyzed data from patients who underwent
      coronary artery bypass grafting, valve surgery or a combination of both at the
      University Hospital Muenster between April 2014 and July 2015. We evaluated the
      incidence of new onset and intermittent/permanent AF (patients with pre- and
      postoperative AF). Furthermore, we investigated the impact of postoperative AF on
      clinical outcomes and evaluated potential risk factors. RESULTS: In total, 999
      patients were included in the analysis. New onset AF occurred in 24.9% of the
      patients and the incidence of intermittent/permanent AF was 59.5%. Both types of
      postoperative AF were associated with prolonged ICU length of stay (median
      increase approx. 2 days) and duration of mechanical ventilation (median increase
      1 h). Additionally, new onset AF patients had a higher rate of dialysis and
      hospital mortality and more positive fluid balance on the day of surgery and
      postoperative days 1 and 2. In a multiple logistic regression model, advanced age
      (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG
      and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06
      per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287
      per unit increase, p = 0.032) significantly predicted new onset AF. Higher
      Horowitz index values were associated with a reduced risk (OR = 0.996 per unit
      increase, p = 0.012). In a separate model, higher plasma creatinine concentration
      (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for
      intermittent/permanent AF whereas higher plasma phosphate concentration (OR =
      0.522 per unit increase, p = 0.003) indicated reduced occurrence of this
      arrhythmia. CONCLUSIONS: New onset and intermittent/permanent AF are associated
      with adverse clinical outcomes of elective cardiac surgery patients. Different
      risk factors implicated in postoperative AF suggest different mechanisms might be
      involved in its pathogenesis. Customized clinical management protocols seem to be
      warranted for a higher success rate of prevention and treatment of postoperative
      AF.

PMID- 29197341
TI  - Frail phenotype is associated with distinct quantitative electroencephalographic
      findings among end-stage renal disease patients: an observational study.
AB  - BACKGROUND: Frailty is prevalent among patients with end-stage renal disease
      (ESRD) and is associated with an increased risk of cognitive impairment. However,
      apart from its influence on cognition, it is currently unknown whether frailty
      affects subtler cerebral function in patients with ESRD. METHODS: Patients with
      ESRD were prospectively enrolled, with clinical features and laboratory data
      recorded. The severity of frailty among these patients with ESRD was ascertained
      using the previously validated simple FRAIL scale, and was categorized as none-to
      mild and moderate-to-severe frailty. All participants underwent quantitative
      electroencephalography (EEG), with band powers documented following the
      generation of the delta to alpha ratio (DAR) and delta/theta to alpha/beta ratio
      (DTABR). EEG results were then compared between groups of different levels of
      frailty. RESULTS: In this cohort, (mean age: 68.9 +/- 10.4 years, 37% male, 3.4
      +/- 3 years of dialysis), 20, 60, 40, 17, and 6% patients exhibited positivity in
      the fatigue, resistance, ambulation, illness, and loss-of-body-weight domains,
      respectively, with 45.7% being none to mildly frail and 54.3% being moderately to
      severely frail. Those with mild frailty had a significantly higher delta power
      compared to those with more severe frailty, involving all topographic sites.
      Patients with ESRD and severe frailty had significantly lower global, left
      frontal, left temporo-occipital, and right temporo-occipital DAR and DTABR,
      except in the right frontal area, and tended to have central accentuation of
      alpha, beta, and theta power, and more homogeneous DTABR and DAR distribution
      compared to the findings in those with mild frailty. CONCLUSIONS: Frailty in
      patients with ESRD can have subtler neurophysiological influences, presenting as
      altered EEG findings, which warrant our attention.

PMID- 29197342
TI  - Identification and integrated analysis of differentially expressed lncRNAs and
      circRNAs reveal the potential ceRNA networks during PDLSC osteogenic
      differentiation.
AB  - BACKGROUND: Researchers have been exploring the molecular mechanisms underlying
      the control of periodontal ligament stem cell (PDLSC) osteogenic differentiation.
      Recently, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were shown
      to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of
      microRNAs (miRNAs) on their target genes during cell differentiation. However,
      comprehensive identification and integrated analysis of lncRNAs and circRNAs
      acting as ceRNAs during PDLSC osteogenic differentiation have not been performed.
      RESULTS: PDLSCs were derived from healthy human periodontal ligament and cultured
      separately with osteogenic induction and normal media for 7 days. Cultured PDLSCs
      were positive for STRO-1 and CD146 and negative for CD31 and CD45. Osteo-induced
      PDLSCs showed increased ALP (alkaline phosphatase) activity and up-regulated
      expression levels of the osteogenesis-related markers ALP, Runt-related
      transcription factor 2 and osteocalcin. Then, a total of 960 lncRNAs and 1456
      circRNAs were found to be differentially expressed by RNA sequencing. The
      expression profiles of eight lncRNAs and eight circRNAs were measured with
      quantitative real-time polymerase chain reaction and were shown to agree with the
      RNA-seq results. Furthermore, the potential functions of lncRNAs and circRNAs as
      ceRNAs were predicted based on miRanda and were investigated using Gene Ontology
      and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 147 lncRNAs and
      1382 circRNAs were predicted to combine with 148 common miRNAs and compete for
      miRNA binding sites with 744 messenger RNAs. These mRNAs were predicted to
      significantly participate in osteoblast differentiation, the MAPK pathway, the
      Wnt pathway and the signaling pathways regulating pluripotency of stem cells.
      Among them, lncRNAs coded as TCONS_00212979 and TCONS_00212984, as well as
      circRNA BANP and circRNA ITCH, might interact with miRNA34a and miRNA146a to
      regulate PDLSC osteogenic differentiation via the MAPK pathway. CONCLUSIONS: This
      study comprehensively identified lncRNAs/circRNAs and first integrated their
      potential ceRNA function during PDLSC osteogenic differentiation. These findings
      suggest that specific lncRNAs and circRNAs might function as ceRNAs to promote
      PDLSC osteogenic differentiation and periodontal regeneration.

PMID- 29197343
TI  - Expression and evolutionary patterns of mycobacteriophage D29 and its temperate
      close relatives.
AB  - BACKGROUND: Mycobacteriophages are viruses that infect Mycobacterium hosts. A
      large collection of phages known to infect the same bacterial host strain -
      Mycobacterium smegmatis mc2155 - exhibit substantial diversity and
      characteristically mosaic architectures. The well-studied lytic mycobacteriophage
      D29 appears to be a deletion derivative of a putative temperate parent, although
      its parent has yet to be identified. RESULTS: Here we describe three newly
      isolated temperate phages - Kerberos, Pomar16 and StarStuff - that are related to
      D29, and are predicted to be very close relatives of its putative temperate
      parent, revealing the repressor and additional genes that are lost in D29.
      Transcriptional profiles show the patterns of both lysogenic and lytic gene
      expression and identify highly-expressed, abundant, stable, small non-coding
      transcripts made from the Pleft early lytic promoter, and which are toxic to M.
      smegmatis. CONCLUSIONS: Comparative genomics of phages D29, Kerberos, Pomar16 and
      StarStuff provide insights into bacteriophage evolution, and comparative
      transcriptomics identifies the pattern of lysogenic and lytic expression with
      unusual features including highly expressed, small, non-coding RNAs.

PMID- 29197344
TI  - Lactation-related metabolic mechanism investigated based on mammary gland
      metabolomics and 4 biofluids' metabolomics relationships in dairy cows.
AB  - BACKGROUND: Lactation is extremely important for dairy cows; however, the
      understanding of the underlying metabolic mechanisms is very limited. This study
      was conducted to investigate the inherent metabolic patterns during lactation
      using the overall biofluid metabolomics and the metabolic differences from non
      lactation periods, as determined using partial tissue-metabolomics. We analyzed
      the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine)
      and their relationships in six mid-lactation Holstein cows and compared their
      mammary gland (MG) metabolomic profiles with those of six non-lactating cows by
      using gas chromatography-time of flight/mass spectrometry. RESULTS: In total, 33
      metabolites were shared among the four biofluids, and 274 metabolites were
      identified in the MG tissues. The sub-clusters of the hierarchical clustering
      analysis revealed that the rumen fluid and serum metabolomics profiles were
      grouped together and highly correlated but were separate from those for milk.
      Urine had the most different profile compared to the other three biofluids.
      Creatine was identified as the most different metabolite among the four biofluids
      (VIP = 1.537). Five metabolic pathways, including gluconeogenesis, pyruvate
      metabolism, the tricarboxylic acid cycle (TCA cycle), glycerolipid metabolism,
      and aspartate metabolism, showed the most functional enrichment among the four
      biofluids (false discovery rate < 0.05, fold enrichment >2). Clear
      discriminations were observed in the MG metabolomics profiles between the
      lactating and non-lactating cows, with 54 metabolites having a significantly
      higher abundance (P < 0.05, VIP > 1) in the lactation group. Lactobionic acid,
      citric acid, orotic acid and oxamide were extracted by the S-plot as potential
      biomarkers of the metabolic difference between lactation and non-lactation. The
      TCA cycle, glyoxylate and dicarboxylate metabolism, glutamate metabolism and
      glycine metabolism were determined to be pathways that were significantly
      impacted (P < 0.01, impact value >0.1) in the lactation group. Among them, the
      TCA cycle was the most up-regulated pathway (P < 0.0001), with 7 of the 10
      related metabolites increased in the MG tissues of the lactating cows.
      CONCLUSIONS: The overall biofluid and MG tissue metabolic mechanisms in the
      lactating cows were interpreted in this study. Our findings are the first to
      provide an integrated insight and a better understanding of the metabolic
      mechanism of lactation, which is beneficial for developing regulated strategies
      to improve the metabolic status of lactating dairy cows.

PMID- 29197345
TI  - Perioperative Duloxetine and Etoricoxibto improve postoperative pain after lumbar
      Laminectomy: a randomized, double-blind, controlled study.
AB  - BACKGROUND: Duloxetine, Etoricoxib and opioid are of the commonly administered
      drugs in Lumbar laminectomy. The aim of this study is to assess the effect of
      perioperative use of Duloxetine in combination with Etoricoxib on postoperative
      pain and opioid requirements. METHODS: One hundred twenty patients with ASA
      physical status were enrolled with age between 18 and 70 years. Patients were
      divided randomly into four groups of 30 patients: group P received placebo, group
      E received etoricoxib 120 mg, group D received duloxetine 60 mg and group D/E
      received duloxetine 60 mg capsules and etoricoxib 120 mg; 1 h before surgery and
      24 h after. RESULTS: Neither Duloxetine nor etoricoxib individually had effect on
      pain with movement, while their combination revealed a significant reduction in
      pain scores over the entire postoperative period at rest and on movement.
      Etoricoxib showed a significant decrease in pain at all times at rest when
      compared with group P, while it showed significant pain decrease only at 0, 2 and
      4 h when compared with group D. On the other hand duloxetine alone showed
      significant decrease in pain at rest at 24 h and 48 h when compared with group P.
      ConcerningMorphine requirement after 24 h.; it wassignificantly lower in the D/E
      group in comparison with groups P, E and D. It should be noted also that there
      was a significant decrease morphine requirement in both groups E and D.
      CONCLUSION: The perioperative administration of the combination of etoricoxib and
      duloxetine improved analgesia and reduced opioid consumption without significant
      side effects. TRIAL REGISTRATION: ISRCTN48329522 . 17 June 2017.

PMID- 29197346
TI  - Radiographic features of Ollier's disease - two case reports.
AB  - BACKGROUND: Ollier's disease is a non-hereditary, benign bone tumor which is
      usually characterized by presence of multiple radiolucent lesions (enchondromas)
      in the metaphysis of long bones with unilateral predominance. The disease is a
      rare clinical entity with 1/100000 occurrence in early childhood. Patients mostly
      present with multiple hard swellings and deformity of the tubular bones specially
      hands and feet with leg discrepancy and pathologic fractures. CASE PRESENTATION:
      We present two cases of Ollier's disease in a 13 years old female and 8 years old
      boy which had no specific symptoms. The girl had multiple hard swellings and
      deformity in the fingers of both hands and left toes with left leg deformity and
      discrepancy. Her plain radiographs demonstrated multiple expansile enchondromas
      in the phalanges of hands, left toes and metaphyses of upper humeri as well as
      left leg bones. The enchondromas were also noted in the left iliac bone and
      anterior end of ribs. The boy had bowing deformity and shortage of left leg with
      multiple enchondromas in the metaphyses of left femur, left tibia and fibula as
      well as left iliac bone in his radiographic images. CONCLUSION: Ollier's disease
      is usually diagnosed by clinical signs and typical location of enchondromas
      across skeleton in conventional radiography. It usually does not need specific
      treatment. Well understanding of the clinical manifestation and radiographic
      features can prevent unnecessary application of other imaging modalities; while
      other diagnostic imaging modalities like MRI, ultrasound and scintigraphy can be
      used in complicated and painful conditions.

PMID- 29197347
TI  - Sample size calculations based on a difference in medians for positively skewed
      outcomes in health care studies.
AB  - BACKGROUND: In healthcare research, outcomes with skewed probability
      distributions are common. Sample size calculations for such outcomes are
      typically based on estimates on a transformed scale (e.g. log) which may
      sometimes be difficult to obtain. In contrast, estimates of median and variance
      on the untransformed scale are generally easier to pre-specify. The aim of this
      paper is to describe how to calculate a sample size for a two group comparison of
      interest based on median and untransformed variance estimates for log-normal
      outcome data. METHODS: A log-normal distribution for outcome data is assumed and
      a sample size calculation approach for a two-sample t-test that compares log
      transformed outcome data is demonstrated where the change of interest is
      specified as difference in median values on the untransformed scale. A simulation
      study is used to compare the method with a non-parametric alternative (Mann
      Whitney U test) in a variety of scenarios and the method is applied to a real
      example in neurosurgery. RESULTS: The method attained a nominal power value in
      simulation studies and was favourable in comparison to a Mann-Whitney U test and
      a two-sample t-test of untransformed outcomes. In addition, the method can be
      adjusted and used in some situations where the outcome distribution is not
      strictly log-normal. CONCLUSIONS: We recommend the use of this sample size
      calculation approach for outcome data that are expected to be positively skewed
      and where a two group comparison on a log-transformed scale is planned. An
      advantage of this method over usual calculations based on estimates on the log
      transformed scale is that it allows clinical efficacy to be specified as a
      difference in medians and requires a variance estimate on the untransformed
      scale. Such estimates are often easier to obtain and more interpretable than
      those for log-transformed outcomes.

PMID- 29197348
TI  - Hyperbaric oxygen treatment and nephrotoxicity induced by gentamicin in rats.
AB  - BACKGROUND: Nephrotoxicity is a significant adverse side effect of gentamicin.
      Previous preclinical studies showed that hyperbaric oxygen treatment (HBOT) may
      have beneficial effects by attenuating renal damage in rats subjected to renal
      injury. We evaluated the effect of HBOT on acute renal failure caused by
      gentamicin. METHODS: Thirty-six rats were divided into four groups. Gentamicin
      (150 mg/kg for 5 consecutive days) was administered in 30 rats, 10 rats received
      only gentamicin, 10 rats received 100% oxygen therapy on days 1-5 of the
      experiment, 10 received daily HBOT on days 1-5 of the experiment, and the
      remaining six served as a control group. On day 6, renal function tests and renal
      pathological examinations were performed. RESULTS: Body weight and biochemical
      parameters were similar in all groups except for higher plasma levels of calcium
      in the 100% oxygen group (P = 0.03). All the rats in the experimental group
      showed biochemical parameters compatible with renal failure (high serum levels of
      urea and creatinine). All the rats in the control group had normal renal function
      tests. Two rats from the HBOT group died on the fifth day of the experiment. All
      rats in the control group demonstrated normal renal morphology. All 28
      intoxicated rats showed moderate to severe histopathological changes without
      significant differences between the groups. CONCLUSIONS: Treatment of gentamicin
      induced nephrotoxicity with either HBOT or 100% oxygen for 5 days had no
      beneficial renal effect. Mortality was observed only in the HBOT group.

PMID- 29197349
TI  - Granulomatous interstitial nephritis due to chronic lymphocytic leukemia: a case
      report.
AB  - BACKGROUND: Renal failure due to the infiltration of chronic lymphocytic leukemia
      (CLL) cells into the tubulointerstitial area of the kidney is uncommon.
      Furthermore, granulomatous interstitial nephritis (GIN) is a rare histological
      diagnosis in patients undergoing a renal biopsy. We herein report a case of GIN
      due to the diffuse infiltration of CLL cells in a patient who developed
      progressive renal failure. CASE PRESENTATION: The patient was a 55-year-old man
      who had been diagnosed with CLL 4 years earlier and who had been followed up
      without treatment. Although his serum creatinine level had remained normal for
      three and a half years, it started to increase in the six months prior to his
      presentation. A urinalysis showed mild proteinuria without any hematuria at the
      time of presentation. A renal biopsy revealed the diffuse infiltration of CLL
      cells into the tubulointerstitial area with non-caseating epithelioid cell
      granulomas. Despite cyclophosphamide treatment, his renal function did not
      improve, and he ultimately required maintenance hemodialysis. CONCLUSION: When
      progressive renal failure is combined with CLL, GIN due to the direct
      infiltration of CLL cells should be considered as a differential diagnosis.

PMID- 29197350
TI  - Effect of hyperchloremia on acute kidney injury in critically ill septic
      patients: a retrospective cohort study.
AB  - BACKGROUND: Hyperchloremia is common in critically ill septic patients. The
      impact of hyperchloremia on the incidence of acute kidney injury (AKI) is not
      well studied. We investigated the association between hyperchloremia and AKI
      within the first 72 h of intensive care unit (ICU) admission. METHODS: 6490 ICU
      adult patients admitted with severe sepsis or septic shock were screened for
      eligibility. Exclusion criteria included: AKI on admission, baseline estimated
      glomerular filtration rate (eGFR) <15 ml/min/1.73 m2, chronic renal replacement
      therapy, absent baseline serum creatinine data, and absent serum chloride data on
      ICU admission. RESULTS: A total of 1045 patients were available for analysis
      following the implementation of eligibility criteria: 303 (29%) had
      hyperchloremia (Cl0 >= 110 mEq/L) on ICU admission, 561 (54%) were normochloremic
      (Cl0 101-109 mEq/L) and 181 (17%) were hypochloremic (Cl0 <= 100 mEq/L). AKI
      within the first 72 h of ICU stay was the dependent variable. Chloride on ICU
      admission (Cl0) and change in Cl by 72 h (DeltaCl = Cl72 - Cl0) were the
      independent variables. The odds for AKI were not different in the hyperchloremic
      group when compared to the normochloremic group [adjusted odds ratio (OR) =0.80,
      95% confidence interval [CI] (0.51-1.25); p = 0.33] after adjusting for
      demographics, comorbidities, baseline kidney function, drug exposure and critical
      illness indicators including cumulative fluid balance and base deficit.
      Furthermore, within the subgroup of patients with hyperchloremia on ICU
      admission, neither Cl0 nor DeltaCl was associated with AKI or with
      moderate/severe AKI (KDIGO Stage >=2). CONCLUSIONS: Hyperchloremia occurs
      commonly among critically ill septic patients admitted to the ICU, but does not
      appear to be associated with an increased risk for AKI within the first 72 h of
      admission.

PMID- 29197351
TI  - Maternal characteristics and birth outcomes resulting from births before arrival
      at health facilities in Nkangala District, South Africa: a case control study.
AB  - BACKGROUND: Risks of severe, avoidable maternal and neonatal complications at
      birth are increased if the birth occurs before arrival at the health facility and
      in the absence of skilled birth attendants. Birth Before Arrival (BBA) is a
      preventable phenomenon still common in modern-day practice despite extensive
      improvements made in obstetric care and in accessibility to healthcare in South
      Africa. This study aimed to determine the risk factors and outcomes in mothers
      and babies associated with being born before arrival at hospitals. METHODS: A
      prospective case control study design was conducted. All BBAs presenting to the
      hospitals in Nkangala District between November 2015 and February 2016 were
      included and compared to a consecutive hospital delivery occurring immediately
      after the arrival of each BBA. T-tests and chi square tests were used to analyse
      the differences between the groups and a binary logistic regression analysis used
      to determine predictors of BBAs. All statistical analysis were done using STATA
      version 14 using a 5% decision level and a 95% confidence interval. RESULTS:
      During the study period, 4397 in-facility births and 201 BBAs were recorded, 78
      BBAs and 75 controls were investigated in this study. The district BBA prevalence
      was 4.6%. Risk factors identified in mothers of BBAs were: single mothers (83.3%
      vs 69.3%; p = 0.04); residing in an informal settlement (23.1% vs 5.3%; p =
      0.002); and higher gravidity with plurigravida significantly more (60.3% vs
      32.5%; p < 0.0001). A prevalent maternal complication in cases was haemorrhage
      due to retained placenta. Most neonates were born alive with a higher proportion
      of cases experiencing perinatal complications such as respiratory distress,
      hypothermia and asphyxia. No significant differences in maternal age, employment
      status and immediate birth outcomes were found. Residing in informal settlements,
      higher gravidity, unplanned pregnancy, low birth weight and unbooked were found
      to predict the occurrence of BBAs. CONCLUSION: Although no significant numbers of
      mortalities were recorded in this study, service delivery interventions targeting
      the reduction of BBAs are needed so as to minimise the morbidity experienced by
      the group.

PMID- 29197352
TI  - Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post
      lingual bilateral moderate-to-severe sensorineural hearing loss.
AB  - BACKGROUND: Implementation of whole exome sequencing has provided unique
      opportunity for a wide screening of causative variants in genetically
      heterogeneous diseases, including nonsyndromic hearing impairment. TRIOBP in the
      inner ear is responsible for proper structure and function of stereocilia and is
      necessary for sound transduction. METHODS: Whole exome sequencing followed by
      Sanger sequencing was conducted on patients derived from Polish hearing loss
      family. RESULTS: Based on whole exome analysis, we identified two TRIOBP
      pathogenic variants (c.802_805delCAGG, p.Gln268Leufs*610 and c.5014G>T,
      p.Gly1672*, the first of which was novel) causative of nonsyndromic, peri- to
      postlingual, moderate-to-severe hearing loss in three siblings from a Polish
      family. Typically, TRIOBP pathogenic variants lead to prelingual, severe-to
      profound hearing loss, thus the onset and degree of hearing impairment in our
      patients represent a distinct phenotypic manifestation caused by TRIOBP variants.
      The pathogenic variant p.Gln268Leufs*610 disrupts the TRIOBP-4 and TRIOBP-5
      isoforms (both expressed exclusively in the inner ear and retina) whereas the
      second pathogenic variant c.514G>T, p.Gly1672* affects only TRIOBP-5.
      CONCLUSIONS: The onset and degree of hearing impairment, characteristic for our
      patients, represent a unique phenotypic manifestation caused by TRIOBP pathogenic
      variants. Although TRIOBP alterations are not a frequent cause of hearing
      impairment, this gene should be thoroughly analyzed especially in patients with a
      postlingual hearing loss. A delayed onset of hearing impairment due to TRIOBP
      pathogenic variants creates a potential therapeutic window for future targeted
      therapies.

PMID- 29197353
TI  - Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Epigenetic alterations have been recognized as important contributors
      to the pathogenesis of PDAC. However, the role of histone variants in pancreatic
      tumor progression is still not completely understood. The aim of this study was
      to explore the expression and prognostic significance of histone protein variants
      in PDAC patients. METHODS: Liquid chromatography-tandem mass spectrometry (LC
      MS/MS) was employed for qualitative analysis of histone variants and histone
      related post-translational modifications (PTMs) in PDAC and normal pancreatic
      tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox
      proportional hazards regression. RESULTS: Histone variant H1.3 was found to be
      differentially expressed (p = 0.005) and was selected as a PDAC specific histone
      variant candidate. The prognostic role of H1.3 was evaluated in an external
      cohort of patients with resected PDAC using immunohistochemistry. Intratumor
      expression of H1.3 was found to be an important risk factor for overall survival
      in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1-6.1), p = 0.029.
      CONCLUSION: We suggest that the intratumor histone H1.3 expression as reported
      herein, may serve as a new epigenetic biomarker for PDAC.

PMID- 29197354
TI  - Prevalence of incidental breast cancer and precursor lesions in autopsy studies:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Autopsy studies demonstrate the prevalence pool of incidental breast
      cancer in the population, but estimates are uncertain due to small numbers in any
      primary study. We aimed to conduct a systematic review of autopsy studies to
      estimate the prevalence of incidental breast cancer and precursors. METHODS:
      Relevant articles were identified through searching PubMed and Embase from
      inception up to April 2016, and backward and forward citations. We included
      autopsy studies of women with no history of breast pathology, which included
      systematic histological examination of at least one breast, and which allowed
      calculation of the prevalence of incidental breast cancer or precursor lesions.
      Data were pooled using logistic regression models with random intercepts (non
      linear mixed models). RESULTS: We included 13 studies from 1948 to 2010,
      contributing 2363 autopsies with 99 cases of incidental cancer or precursor
      lesions. More thorough histological examination (>=20 histological sections) was
      a strong predictor of incidental in-situ cancer and atypical hyperplasia (OR =
      126.8 and 21.3 respectively, p < 0.001), but not invasive cancer (OR = 1.1, p =
      0.75). The estimated mean prevalence of incidental cancer or precursor lesion was
      19.5% (0.85% invasive cancer + 8.9% in-situ cancer + 9.8% atypical hyperplasia).
      CONCLUSION: Our systematic review in ten countries over six decades found that
      incidental detection of cancer in situ and breast cancer precursors is common in
      women not known to have breast disease during life. The large prevalence pool of
      undetected cancer in-situ and atypical hyperplasia in these autopsy studies
      suggests screening programs should be cautious about introducing more sensitive
      tests that may increase detection of these lesions.

PMID- 29197355
TI  - Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer
      Xenograft model.
AB  - BACKGROUND: Metastasis refers to the spread of a primary tumor cell from the
      primary site to other locations in the body and it is generally associated with
      the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various
      bioactive compounds and it exerts beneficial effects including improvements in
      brain function and reduced risk of cardiovascular diseases. On the other hand,
      increased risk of thyroid and liver cancers by EGb have been reported in animals.
      METHODS: A colon cancer metastasis model was established using intrasplenic
      injection of a human colon cancer cell line, SW620-luc in athymic mice to
      investigate the potential impact of EGb on colon cancer progression. After tumor
      establishment, EGb was intraperitonically injected daily for 5 wks. RESULTS: EGb
      significantly increased the rate of metastasis in mouse liver and decreased the
      number of necrotic and apoptotic cells in the metastatic liver when compared to
      the control. Meanwhile, EGb significantly induced proliferation of tumor cells in
      the metastatic liver, indicated by increased staining of Ki67 and H3S10p. mRNA
      expression of genes involved in cell cycle, metastasis, apoptosis, and oxidative
      stress were altered by EGb treatment in livers with tumors. Moreover, EGb
      activated the stress-responsive MAPK pathways in the liver with metastatic
      tumors. CONCLUSIONS: EGb exacerbated liver metastasis in a mouse colon cancer
      metastasis model. This is potentially due to the increased tumor cell
      proliferation involving stimulated MAPK pathways.

PMID- 29197356
TI  - Social and health outcomes following upgrades to a national housing standard: a
      multilevel analysis of a five-wave repeated cross-sectional survey.
AB  - BACKGROUND: While existing research indicates that housing improvements are
      associated with health improvements, less is known about the wider social and
      health benefits of meeting national housing standards, as well as those of their
      specific constituent measures. This study evaluates the impacts of a managed
      housing upgrade programme through a repeated cross-sectional survey design.
      METHODS: A five-wave repeated cross-sectional survey was conducted over a seven
      year period from 2009 to 2016 (n = 2075; n = 2219; n = 2015; n = 1991; and n =
      1709, respectively). The study followed a managed upgrade programme designed to
      meet a national social housing standard over an extended period. The data were
      analysed from a multilevel perspective to take account of the time-dependent
      nature of the observations and differences in socio-demographic composition.
      RESULTS: The installation of the majority of individual housing measures (new
      windows and doors; boilers; kitchens; bathrooms; electrics; loft insulation; and
      cavity/external wall insulation) were associated with improvements in several
      social (housing suitability, satisfaction, and quality; thermal comfort and
      household finances) and health (mental, respiratory and general health) outcomes;
      and analyses showed relationships between the number of measures installed and
      the total amount invested on the one hand and the social and health outcomes on
      the other. There were however a few exceptions. Most notably, the installation of
      cavity wall insulation was associated with poorer health outcomes, and did not
      lead to better social outcomes. Also, no association was found between the number
      of measures installed and respiratory health. CONCLUSIONS: The study suggests
      that substantial housing investments through a managed upgrade programme may
      result in better social and health outcomes, and that the size of the
      improvements are proportionate to the number of measures installed and amount
      invested. However, there may be risks associated with specific measures; and more
      attention is needed for mechanical ventilation when upgrading energy efficiency
      of houses through fabric work. In addition to providing new evidence regarding
      the wider social and health outcomes, the study provides an analytical approach
      to evaluate upgrade programmes that are delivered over multiple years.

PMID- 29197357
TI  - Assessing the outcomes of HIV-infected persons receiving treatment for Kaposi
      sarcoma in Conakry-Guinea.
AB  - BACKGROUND: Medecins Sans Frontieres is supporting comprehensive HIV care and
      treatment for Kaposi Sarcoma (KS) in Guinea, where antiretroviral coverage is low
      and access to KS treatment is very limited. We aimed to evaluate treatment
      response and survival outcomes of epidemic KS in this setting. METHODS:
      Retrospective survival analysis of routinely collected clinical data of HIV
      infected patients with clinically diagnosed KS, receiving ART and chemotherapy
      consisting of a combination of bleomycin and vincristine at the Donka National
      Hospital in Conakry between 2012 and 2015. RESULTS: A total of 225 patients were
      enrolled for KS treatment within the three-year period. Late presentation with
      stage T1 disease was common (82.7%). At the end of a median of 8 cycles of
      chemotherapy (IQR: 2-12), complete remission was observed in 65 (28.9%), partial
      remission in 53 (23.6%), stable disease in 15 (6.7%) and unknown response for all
      92 (40.9%) patients who dropped out of care. The chances of achieving complete
      remission doubled after each additional cycle of chemotherapy (aOR = 2.09 95% CI:
      1.44-3.01) but were reduced by about two-thirds for each additional month delay
      between treatment and onset of KS (aOR = 0.31, 95% CI: 0.11-0.86). Treatment
      response was seriously compromised in patients with woody skin oedema (aOR =
      0.05, 95% CI: 0.01-0.38) and those with prior chemotherapy (aOR = 0.21, 95% CI:
      0.05-0.80). The median survival time was 7.6 months (95% CI: 5.9-9.8). Attrition
      from care was reduced by 22% for every additional cycle of chemotherapy
      administered (aH0R = 0.78, 95% CI: 0.71-0.84) and was lower in those with
      complete remission compared with those with partial or no response (aHR = 0.05,
      95% CI: 0.007-0.43). CONCLUSION: There has been an increased access to KS
      treatment. The overall response rate is 52.4%, which is considered a satisfactory
      result. Poor outcomes were common and were largely due to late presentation and
      defaulting on treatment. Efforts towards early HIV/KS diagnosis and adherence to
      a full round of chemotherapy are needed for optimising outcomes. Newer drugs may
      be required for patients previously exposed to chemotherapy.

PMID- 29197358
TI  - The inhibitory effects of compound Muniziqi granule against B16 cells and harmine
      induced autophagy and apoptosis by inhibiting Akt/mTOR pathway.
AB  - BACKGROUND: Compound Muniziqi granule (MNZQ) is a multi-component herbal
      preparation and a popular traditional Uighur medicine used in China for treating
      endocrine disorder-induced acne, chloasma, dysmenorrhea, menopausal syndrome, and
      melanoma. Harmine presented in MNZQ has been confirmed potential anticancer
      effect on the B16 cells among others. The purpose of this study is to explore the
      inhibitory effects of MNZQ against B16 cells and mechanism of autophagy and
      apoptosis induced by harmine in B16 cells. METHODS: The cell viability was
      calculated by CCK8 assay. The in vitro tyrosinase activity was determined by
      spectrophotometry. The harmine-induced autophagy was demonstrated by electron
      microscopy and MDC staining. Flow cytometry was used to measure cell death and
      cell cycle distribution. All proteins expression was assessed by western blot.
      RESULTS: MNZQ and some herb extracts contained in preparation displayed
      inhibitory effects on B16 cells but without inhibition on mushroom tyrosinase
      compared with kojic acid. The formation of autophagosome was markedly induced by
      harmine with the accretion of LC3-II and the degeneration of p62 in B16 cells,
      which indicated that harmine was an autophagy inducer. Cell death and sub-G2
      population suggested that harmine could induce cell death. Particularly, 3-MA, an
      autophagy inhibitor, was discovered to prevent harmine-induced decrease of the
      cell viability and cell cycle arrest on G2 phase, indicating that autophagy was
      vital to the cell death. In addition, the results indicated that harmine could
      inhibit the phosphorylation of Akt and mTOR, which might mediate autophagy.
      CONCLUSION: Harmine could induce autophagy and apoptosis by inhibiting Akt/mTOR
      pathway in B16 cells. Harmine might be a promising therapeutic agent for
      treatment of melanoma in MNZQ.

PMID- 29197359
TI  - Cultural adaptation and validity of the Malay version of the brief psychiatric
      rating scale (BPRS-M) among patients with schizophrenia in a psychiatric clinic.
AB  - BACKGROUND: This study evaluates the psychometric properties of the Malay version
      of the Brief Psychiatric Rating Scale (BPRS-M) among patients with schizophrenia
      in a psychiatric outpatient clinic. METHODS: Ninety-nine schizophrenia
      outpatients were administered the Malay version of the Brief Psychiatric Rating
      Scale (BPRS-M), Malay version of Positive and Negative Syndrome Scale (PANSS),
      Malay version of Calgary Depression Scale for Schizophrenia (CDSS) and Malay
      version of World Health Organization Quality of Life - Brief Version (WHOQOL
      BREF). RESULTS: An exploratory factor analysis (EFA) of BPRS-M produced a seven
      factor solution which accounted for 71.4% of the total variance. It exhibited
      fair internal consistency (Cronbach's alpha coefficient of 0.75). "Positive
      symptoms" and "Resistance" factors had association with unemployment and number
      of antipsychotics, positively correlated with PANSS but negatively correlated
      with WHOQOL-BREF. "Mood disturbance" factor correlated with lifetime history of
      suicide attempts, Malay version of CDSS and WHOQOL-BREF (psychological). Both
      "Negative symptoms" and "Activation" factors were associated with male, lower
      education, unemployment and positively correlated with Malay version of PANSS but
      negatively correlated with WHOQOL-BREF. CONCLUSIONS: The BPRS-M demonstrated
      promising psychometric properties in terms of dimensionality, reliability, and
      validity that generally justifies its use in routine clinical practice in
      Malaysia.

PMID- 29197360
TI  - Psychometric properties of the expanded prostate cancer index composite - 26
      instrument in a cohort of radical prostatectomy patients: theoretical and
      practical examinations.
AB  - BACKGROUND: Recently, the Expanded Prostate Cancer Index Composite 26-item
      version (EPIC-26) was recommended for the assessment of adverse effects after the
      treatment of prostate cancer without clear reasons. This decision encouraged us
      to review the questionnaire development from the UCLA Prostate Cancer Index (UCLA
      PCI) to the EPIC-16 CP with a focus on psychometric properties. We also reviewed
      PubMed for papers concerning such properties of the EPIC-26 since 2012 (latest
      review in 2011). Finally, we examined the psychometric properties of the EPIC-26
      in a sample of Norwegian males treated with robot-assisted laparoscopic
      prostatectomy (RALP). METHODS: This study used three methods: (1) Comparison of
      the content of the UCLA-PCI, EPIC-50, EPIC-26, and EPIC-16 CP; (2) Review of EPIC
      26 and EPIC-16 CP papers in PubMed from 2012 to 2016, identifying papers
      reporting on the psychometric properties of these questionnaires; and (3)
      Psychometric examination of the EPIC-26 rating in 651 Norwegian men treated with
      RALP at a mean of 3.2 years post-surgery. RESULTS: The questionnaire development
      showed a significant increase in bother versus function items, and the EPIC-26
      contains eight function and 18 bother items. Twelve papers concerning the EPIC-26
      available on PubMed since 2012 support the psychometric properties of the EPIC
      26. The Norwegian EPIC-26 findings supported the psychometric properties of the
      EPIC-26, but suggested six subdomains both by exploratory and confirmatory factor
      analyses. CONCLUSIONS: In general our examinations supported the adequate
      psychometric properties of the EPIC-26, although the factor structure, construct
      and predictive validity of the instrument should be examined further.

PMID- 29197361
TI  - Primary malignant melanoma of the esophagus treated with subtotal esophagectomy:
      a case report.
AB  - BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is a rare disease
      with a poor prognosis. There are few reports of early-stage cases in which tumor
      invasion reached the lamina propria or muscularis mucosae, as in the present
      case. A standard treatment for early-stage PMME has not yet been established. The
      present study aimed to summarize previous reports and to discuss the indications
      for surgical treatment of early-stage primary malignant melanoma of the
      esophagus. CASE PRESENTATION: A 70-year-old woman with PMME was referred to our
      hospital. She underwent thoracoscopic and laparoscopic subtotal esophagectomy
      with lymphadenectomy. The resected specimen showed melanocytosis and junctional
      activity. Melanoma-specific antigens melan-A, S-100, and HMB45 were detected by
      immunohistochemical staining. The pathological diagnosis was pT1a-MM, pN0, pM0,
      and pStage IA. She remains alive without evidence of recurrence 39 months later.
      CONCLUSION: Subtotal esophagectomy with regional radical lymphadenectomy could be
      recommended to patients with early-stage primary malignant melanoma of the
      esophagus, and curative surgical resection could improve their prognosis.

PMID- 29197362
TI  - Evidence for the need for vision screening of school children in Turkey.
AB  - BACKGROUND: In many countries, access to general health and eye care is related
      to an individual's socioeconomic status (SES). We aimed to examine the prevalence
      of oculo-visual disorders in children in Istanbul Turkey, drawn from schools at
      SES extremes but geographically nearby. METHODS: Three school-based vision
      screenings (presenting distance visual acuity, cover test, eye assessment
      history, colour vision, gross stereopsis and non-cycloplegic autorefraction) were
      conducted on 81% of a potential 1014 primary-school children aged 4-10 years from
      two private (high SES) schools and a nearby government (low SES) school in
      central Istanbul. Prevalence of refractive errors and school-based differences
      were analysed using parametric statistics (ANOVA). The remaining oculo-visual
      aspects were compared using non-parametric tests. RESULTS: Of the 823 children
      with mean age 6.7 +/- 2.2 years, approximately 10% were referred for a full eye
      examination (8.2% and 16.3% of private/government schools respectively). Vision
      had not been previously examined in nearly 22% of private school children and 65%
      of government school children. Of all children, 94.5% were able to accurately
      identify the 6/9.5 [LogMAR 0.2] line of letters/shapes with each eye and 86.6%
      the 6/6 line [LogMAR 0], while 7.9% presented wearing spectacles, 3.8% had
      impaired colour vision, 1.5% had grossly impaired stereo-vision, 1.5% exhibited
      strabismus, 1.8% were suspected to have amblyopia and 0.5% had reduced acuity of
      likely organic origin. Of the 804 without strabismus, amblyopia or organic
      conditions, 6.0% were myopic <= - 0.50DS, 0.6% hyperopic >= + 2.00DS, 7.7%
      astigmatic >=1.00 DC and 6.2% anisometropic >=1.00DS. CONCLUSIONS: The results
      highlight the need for general vision screenings for all children prior to school
      entry given the varied and different pattern of visual problems associated with
      lifestyle differences in two populations raised in the same urban locale but
      drawn from different socioeconomic backgrounds.

PMID- 29197363
TI  - Metastatic retinoblastoma of the parotid and submandibular glands: a rare case
      report.
AB  - BACKGROUND: Retinoblastoma is the most common intraocular malignancy occurring in
      children. It can metastasize to the regional lymph nodes, central nervous system
      and distant organs usually the bones and bone marrow and very rarely to the soft
      tissue. Here, we report a case of unilateral retinoblastoma in a 4-year-old girl
      accompanied by a large metastasis of the parotid and submandibular glands that
      developed about 6 months previously and gradually increased in size 5 months
      after enucleation of the left eye. CASE PRESENTATION: A 4-year-old girl with a
      history of unilateral retinoblastoma presented with a large, painful and
      worsening mass (about 20 * 23 cm) of the left side of the neck. Following
      surgery, the orbital tumour was completely resected, and the large tumour
      invasion range in the left side of the neck was not resected completely.
      Histopathological examination revealed retinoblastoma of the orbit and the
      parotid and submandibular glands. After chemotherapy and additional local
      radiotherapy on the parotid and submandibular glands, the tumour was inactive and
      stable. CONCLUSIONS: Delayed detection and inappropriate management contribute to
      poor outcomes. Fundus examinations, education regarding the early signs of RB,
      and optimization of the therapeutic strategy for RB may play important roles in
      ocular health.

PMID- 29197364
TI  - Outcomes of Zika virus infection during pregnancy: contributions to the debate on
      the efficiency of cohort studies.
AB  - BACKGROUND: Zika infection during pregnancy (ZIKVP) is known to be associated
      with adverse outcomes. Studies on this matter involve both rare outcomes and rare
      exposures and methodological choices are not straightforward. Cohort studies will
      surely offer more robust evidences, but their efficiency must be enhanced. We aim
      to contribute to the debate on sample selection strategies in cohort studies to
      assess outcomes associated with ZKVP. A study can be statistically more efficient
      than another if its estimates are more accurate (precise and valid), even if the
      studies involve the same number of subjects. Sample size and specific design
      strategies can enhance or impair the statistical efficiency of a study, depending
      on how the subjects are distributed in subgroups pertinent to the analysis. In
      most ZIKVP cohort studies to date there is an a priori identification of the
      source population (pregnant women, regardless of their exposure status) which is
      then sampled or included in its entirety (census). Subsequently, the group of
      pregnant women is classified according to exposure (presence or absence of
      ZIKVP), respecting the exposed:unexposed ratio in the source population. We
      propose that the sample selection be done from the a priori identification of
      groups of pregnant women exposed and unexposed to ZIKVP. This method will allow
      for an oversampling (even 100%) of the pregnant women with ZKVP and a optimized
      sampling from the general population of pregnant women unexposed to ZIKVP, saving
      resources in the unexposed group and improving the expected number of incident
      cases (outcomes) overall. CONCLUSION: We hope that this proposal will broaden the
      methodological debate on the improvement of statistical power and protocol
      harmonization of cohort studies that aim to evaluate the association between Zika
      infection during pregnancy and outcomes for the offspring, as well as those with
      similar objectives.

PMID- 29197365
TI  - Prevalence of severe early childhood caries and associated socioeconomic and
      behavioral factors in Xinjiang, China: a cross-sectional study.
AB  - BACKGROUND: This study assessed the prevalence and severity of early childhood
      caries (ECC) and identified socioeconomic and behavioral correlates of the
      disease in preschool children living in Xinjiang. METHODS: For this cross
      sectional survey, 1727 children aged 3-5 years in Xinjiang were randomly
      recruited using a three-stage cluster sampling procedure. The "dmft" index
      according to the WHO 1997 criteria was used to assess ECC and severe ECC (S-ECC).
      A questionnaire was completed by caregivers. Variables included sociodemographic
      characteristics, dietary and oral hygiene behaviors, and access to dental
      services. The statistical associations of variables with ECC, S-ECC, and dmft
      were evaluated by univariate and multiple logistic regression analyses. RESULTS:
      The prevalence of ECC was 78.2% and that of S-ECC was 41.2%; mean dmft scores
      were 5.61 +/- 3.56 and 8.17 +/- 2.94, respectively. The prevalence of ECC was
      significantly higher in children from Ining (OR 2.747; 95% CI 2.033-3.713), those
      whose caregivers had caries (OR 1.78; 95% CI 1.245-2.547), those with a dental
      visit in the past (OR 2.023; 95% CI 1.429-2.865), and those whose parents had
      received instructions on oral health care (OR 2.171; 95% CI 1.44-3.272), and
      increased significantly at age 4 years (OR 2.09; 95% CI 1.506-2.901) and 5 years
      (OR 2.666; 95% CI 1.855-3.833) and in children who starting tooth brushing at a
      young age (OR 1.363; 95% CI 1.171-1.587), and decreased significantly in children
      with a more educated mother (OR 0.817; 95% CI 0.688-1), those from high-income
      families (OR 0.667; 95% CI 0.582-0.765), those with low consumption of sweets (OR
      0.66; 95% CI 0.57-0.763), and those who seldom ate before sleep (OR 0.557; 95% CI
      0.437-0.712). CONCLUSIONS: ECC and S-ECC remain a serious problem among preschool
      children in Xinjiang. Caries rates were associated with sociodemographic and
      behavioral factors, which could be modified by public health strategies,
      including protection of primary dentition, extension of insurance to cover oral
      preventive services, improvement of the oral health care system, and public
      health education.

PMID- 29197366
TI  - Characteristics and outcome in patients with non-specific symptoms and signs of
      cancer referred to a fast track cancer patient pathway; a retrospective cohort
      study.
AB  - BACKGROUND: In 2012 a new cancer patient pathway for patients with non-specific
      symptoms and signs of cancer (NSSC-CPP) was introduced in Denmark. Limited
      information is available about the patients referred to the NSSC-CPP and the
      investigational course. The aim was to describe the population and the
      investigational course, estimate the prevalence of cancer and one-year mortality,
      and identify factors associated with a subsequent cancer diagnosis in patients
      referred to the NSSC-CPP. METHOD: This cohort study included patients with at
      least one visit at the NSSC-CPP at North Zealand Hospital in Denmark (NOH) from
      October 1st 2013 to September 30th 2014. Data was based on retrospective reviews
      of the patient files. Logistic regression identified factors associated with a
      subsequent cancer diagnosis. Multivariate analyses were adjusted by age, gender,
      smoking status and alcohol consumption. Kaplan-Meier survival plots were made at
      one-year follow-up. RESULTS: Eight hundred twenty-five patients were included
      with a median age of 67 years, 47.4% were male. Prevalence of cancer within one
      year was 16.7% (138/825). 70.3% (97/138) were solid cancers and 29.7% (41/138)
      were haematological cancers. During the investigational course 76.7% went through
      advanced diagnostic imaging (ultrasound, CT, FDG-PET/CT or MRI). Anaemia (OR1.63
      CI1.02-2.60), leucocytosis (OR 2.06 CI 1.34-3.15), thrombocytopenia (OR 4.13 CI
      2.02-8.47) and elevated LDH (OR 1.64 CI 1.07-2.52) and CRP (OR 2.56 CI 1.66-3.95)
      were associated with a cancer diagnosis when adjusting for possible confounders.
      No single non-specific symptom was significantly associated with a cancer
      diagnosis. One-year mortality for those diagnosed with cancer was 44.2%.
      CONCLUSION: The prevalence of cancer matches that of another NSSC-CPP in Denmark.
      Deviations in basic biochemistry were associated with a higher probability of
      underlying cancer and could possibly raise the level of suspicion of malignancy
      among physicians. High one-year mortality was seen amongst patients diagnosed
      with cancer.

PMID- 29197367
TI  - Success and failure in narrowing the disability employment gap: comparing levels
      and trends across Europe 2002-2014.
AB  - BACKGROUND: International comparisons of the disability employment gap are an
      important driver of policy change. However, previous comparisons have used the
      European Union Statistics on Income and Living Conditions (EU-SILC), despite
      known comparability issues. We present new results from the higher-quality
      European Social Survey (ESS), compare these to EU-SILC and the EU Labour Force
      Survey (EU-LFS), and also examine trends in the disability employment gap in
      Europe over the financial crisis for the first time. METHODS: For cross-sectional
      comparisons of 25 countries, we use micro-data for ESS and EU-SILC for 2012 and
      compare these to published EU-LFS 2011 estimates. For trend analyses, we use
      seven biannual waves of ESS (2002-2014) with a total sample size of 182,195, and
      annual waves of EU-SILC (2004-2014) with a total sample size of 2,412,791.
      RESULTS: (i) Cross-sectional: countries that have smaller disability employment
      gaps in one survey tend to have smaller gaps in the other surveys. Nevertheless,
      there are some countries that perform badly on the lower-quality surveys but
      better in the higher-quality ESS. (ii) Trends: the disability employment gap
      appears to have declined in ESS by 4.9%, while no trend is observed in EU-SILC -
      but this has come alongside a rise in disability in ESS. CONCLUSIONS: There is a
      need for investment in disability measures that are more comparable over
      time/space. Nevertheless, it is clear to policymakers there are some countries
      that do consistently well across surveys and measures (Switzerland), and others
      that do badly (Hungary).

PMID- 29197369
TI  - Age related prevalence of hand osteoarthritis diagnosed by photography
      (HOASCORE).
AB  - BACKGROUND: Hand photography has been used in a number of studies to determine
      the presence and severity of hand osteoarthritis (HOA). The aim of this study was
      to present age and gender specific prevalences of HOA diagnosed by this method.
      METHODS: Six thousand three hundred forty three photographs (from 3676 females
      and 2667 males aged 40-96) were scored for hand osteoarthritis by a 0-3 grade (0
      = no evidence of OA, 1 = possible OA, 2 = definite OA and 3 = severe OA) for each
      of the three main sites, distal interphalangeal joints (DIP), proximal
      interphalangeal joints (PIP) and thumb base (CMC1). An aggregate score of 0-9 was
      thus obtained (HOASCORE) to reflect the severity of HOA in each case. RESULTS:
      DIP joints were most commonly affected, followed by the thumb base and the PIP
      joints. Having definite DIP joint OA starts at a younger age compared with the
      other two sites, and there is a marked female preponderance in the age groups
      from 55 to 69, but after 70 the gender differences are less marked and the
      prevalence is fairly stable. PIP joint prevalence also indicates a female
      preponderance from 60 to 79. Thumb base OA has a more marked female preponderance
      and a rising prevalence thoughout life. The prevalence of individuals with no
      evidence of photographic OA (HOASCORE = 0) drops from 88% to 57% between the age
      categories 40-49 and 50-54 and decreased to 33% in the 70-74 age group with a
      slower decline after that age. DIP and PIP prevalence were strongly associated
      with each other with an OR of 16.6(12.8-21.5),p < 0.001 of having definite OA at
      the other site. This was less marked for the thumb base with an OR of 2.2(1.8
      2.7, p < 0.001), and 2.7(2.0-3.5, p < 0.001) of having definite DIP or PIP HOA
      respectively. CONCLUSIONS: The prevalence of hand OA in DIP, PIP and thumb base
      joints obtained by the photographic HOASCORE method is higher in women and
      increases after the age of fifty. These results are in line with those obtained
      by clinical examination and radiography. The advantage of the method lies in easy
      applicability and low cost.

PMID- 29197368
TI  - An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla
      frutescens Var. acuta and green tea stimulates hair growth in mice.
AB  - BACKGROUND: Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely
      used in Asia for the treatment of patients with alopecia, usually in combination
      with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green
      tea (GT)). However, the effect of this herbal complex has not been clearly
      demonstrated. We sought to determine the hair growth-promoting effect of this
      herbal complex (HC, PFVA, and GT) in the animal model. METHODS: Six-week-old male
      C57BL/6 mice were randomly divided into four groups (negative control,
      finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg)
      concentrations of the herbal complex as experimental groups) and were fed its
      corresponding medications orally for 25 days. Hair growth was evaluated visually
      and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1
      and transforming growth factor (TGF)-beta1 was performed. RESULTS: The herbal
      complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the
      area of hair regrowth was 55.1 (+/-3.8) %, 70.2 (+/-6.3) % and 83.5 (+/-5.7) % in
      negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In
      histologic examination, the hair follicle count in deep subcutis was 2.6 (+/
      0.7), 5.8 (+/-0.7) and 8.6 (+/-1.2) and the diameter of hair follicles was 11.9
      (+/-5.0) MUm, 17.4 (+/-3.9) MUm and 22.8 (+/-5.2) MUm in negative control, herbal
      complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14
      (+/-0.01), 0.23 (+/-0.02) and 0.24 (+/-0.01) and the expression of TGF-beta1 was
      0.26 (+/-0.01), 0.19 (+/-0.02) and 0.15 (+/-0.01) in negative control, the 200
      and 400 mg/kg group, respectively. CONCLUSIONS: This data provides adequate
      preliminary experimental evidence to support the hair regeneration effect of this
      herbal complex.

PMID- 29197370
TI  - Tocolytic action and underlying mechanism of galetin 3,6-dimethyl ether on rat
      uterus.
AB  - BACKGROUND: Galetin 3,6-dimethyl ether (FGAL) is a flavonoid isolated from aerial
      parts of Piptadenia stipulacea. Previously, FGAL was shown to inhibit both
      carbachol- and oxytocin-induced phasic contractions in the rat uterus, which was
      more potent with oxytocin. Thus, in this study, we aimed to investigate the
      tocolytic action mechanism of FGAL on the rat uterus. METHODS: Segments of rat
      uterus ileum were suspended in organ bath containing modified Locke-Ringer
      solution at 32  degrees C, bubbled with carbogen mixture under a resting tension
      of 1 g. Isotonic contractions were registered using kymographs and isometric
      contractions using force transducer. RESULTS: FGAL was more potent in relaxing
      uterus pre-contracted with oxytocin than with KCl. Additionally, FGAL shifted
      oxytocin-induced cumulative contractions curves to the right in a non-parallel
      manner, with Emax reduction, indicating a pseudo-irreversible noncompetitive
      antagonism of oxytocin receptors (OTR) or a downstream pathway target. Moreover,
      FGAL shifted CaCl2-induced cumulative contraction curves to the right in a non
      parallel manner in depolarizing medium, nominally without Ca2+, with Emax
      reduction, suggesting the inhibition of Ca2+ influx through CaV. The relaxant
      potency of FGAL was reduced by CsCl, a non-selective K+ channel blocker,
      suggesting positive modulation of these channels. Furthermore, in presence of
      apamin, 4-aminopyridine, glibenclamide or 1 mM TEA+, the relaxant potency of FGAL
      was attenuated, indicating the participation of SKCa, KV, KATP and highlighting
      BKCa. Aminophylline, a non-selective phosphodiesterase (PDE) blocker, did not
      affect the FGAL relaxant potency, excluding the modulation of cyclic nucleotide
      PDEs pathway by FGAL. CONCLUSION: Tocolytic effect of FGAL on rat uterus occurs
      by pseudo-irreversible noncompetitive antagonism of OTR and activation of K+
      channels, primarily BKCa, leading to calcium influx reduction through CaV.

PMID- 29197372
TI  - The choice that matters: the relative influence of socioeconomic status
      indicators on chronic back pain- a longitudinal study.
AB  - BACKGROUND: In health research, indicators of socioeconomic status (SES) are
      often used interchangeably and often lack theoretical foundation. This makes it
      difficult to compare results from different studies and to explore the
      relationship between SES and health outcomes. To aid researchers in choosing
      appropriate indicators of SES, this article proposes and tests a theory-based
      selection of SES indicators using chronic back pain as a health outcome. METHODS:
      Strength of relationship predictions were made using Brunner & Marmot's model of
      'social determinants of health'. Subsequently, a longitudinal study was conducted
      with 66 patients receiving in-patient treatment for chronic back pain.
      Sociodemographic variables, four SES indicators (education, job position, income,
      multidimensional index) and back pain intensity and disability were obtained at
      baseline. Both pain dimensions were assessed again 6 months later. Using linear
      regression, the predictive strength of each SES indicator on pain intensity and
      disability was estimated and compared to the theory based prediction. RESULTS:
      Chronic back pain intensity was best predicted by the multidimensional index
      (beta = 0.31, p < 0.05), followed by job position (beta = 0.29, p < 0.05) and
      education (beta = -0.29, p < 0.05); whereas, income exerted no significant
      influence. Back pain disability was predicted strongest by education (beta = 
      0.30, p < 0.05) and job position (beta = 0.29, p < 0.05). Here, multidimensional
      index and income had no significant influence. CONCLUSIONS: The choice of SES
      indicators influences predictive power on both back pain dimensions, suggesting
      SES predictors cannot be used interchangeably. Therefore, researchers should
      carefully consider prior to each study which SES indicator to use. The introduced
      framework can be valuable in supporting this decision because it allows for a
      stable prediction of SES indicator influence and their hierarchy on a specific
      health outcomes.

PMID- 29197371
TI  - Partnering around cancer clinical trials (PACCT): study protocol for a randomized
      trial of a patient and physician communication intervention to increase minority
      accrual to prostate cancer clinical trials.
AB  - BACKGROUND: Cancer clinical trials are essential for testing new treatments and
      represent state-of-the-art cancer treatment, but only a small percentage of
      patients ever enroll in a trial. Under-enrollment is an even greater problem
      among minorities, particularly African Americans, representing a racial/ethnic
      disparity in cancer care. One understudied cause is patient-physician
      communication, which is often of poor quality during clinical interactions
      between African-American patients and non-African-American physicians. Partnering
      Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical
      model proposing that patient and physician individual attitudes and beliefs and
      their interpersonal communication during racially discordant clinical
      interactions influence outcomes related to patients' decisions to participate in
      a trial. The overall goal of the study is to test a multilevel intervention
      designed to increase rates at which African-American and White men with prostate
      cancer make an informed decision to participate in a clinical trial.
      METHODS/DESIGN: Data collection will occur at two NCI-designated comprehensive
      cancer centers. Participants include physicians who treat men with prostate
      cancer and their African-American and White patients who are potentially eligible
      for a clinical trial. The study uses two distinct research designs to evaluate
      the effects of two behavioral interventions, one focused on patients and the
      other on physicians. The primary goal is to increase the number of patients who
      decide to enroll in a trial; secondary goals include increasing rates of
      physician trial offers, improving the quality of patient-physician communication
      during video recorded clinical interactions in which trials may be discussed,
      improving patients' understanding of trials offered, and increasing the number of
      patients who actually enroll. Aims are to 1) determine the independent and
      combined effects of the two interventions on outcomes; 2) compare the effects of
      the interventions on African-American versus White men; and 3) examine the extent
      to which patient-physician communication mediates the effect of the interventions
      on the outcomes. DISCUSSION: PACCT has the potential to identify ways to increase
      clinical trial rates in a diverse patient population. The research can also
      improve access to high quality clinical care for African American men bearing the
      disproportionate burden of disparities in prostate and other cancers. TRIAL
      REGISTRATION: Clinical Trials.gov registration number: NCT02906241 (September 8,
      2016).

PMID- 29197373
TI  - Health-related quality of life in long-term survivors of unresectable locally
      advanced non-small cell lung cancer.
AB  - BACKGROUND: Heath-related quality of life (HRQoL) among survivors with
      unresectable locally-advanced non-small cell lung cancer (LA-NSCLC) treated with
      radiotherapy and chemotherapy still is not clear. The current study were
      performed to determine HRQoL for long-term survivors with unresectable LA-NSCLC
      and to identify risk factors for poor HRQoL. METHODS: Among patients with LA
      NSCLC receiving radiotherapy and chemotherapy between January 2006 and December
      2010, 82 long-term survivors beyond 5 years were identified in this cross
      sectional study. The European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ)-C30 and the lung cancer-specific
      questionnaire QLQ-LC13 were employed to gather information on HRQoL. HRQoL scores
      were compared between different subgroups to analyze factors related to HRQoL.
      RESULTS: Fifty-five out of 82 (67%) long-term survivors completed the HRQoL
      survey. They reported a mild reduction in global health status and physical and
      emotional functioning. Fatigue, dyspnea, coughing, and financial difficulties
      ranked the highest scores in the symptom scales. Analysis of risk factors for
      HRQoL showed age, exercise, smoking status, and treatment regimen were associated
      with global health status and functional scores, while age, gender, radiation
      pneumonitis, weight loss, and exercise were associated with symptom scores.
      CONCLUSIONS: This study provides the first description of the HRQoL of long-term
      LA-NSCLC survivors receiving radiotherapy and chemotherapy who may experience a
      relatively high HRQoL. Factors related to poorer HRQoL are potential targets for
      intervention.

PMID- 29197374
TI  - Prevalence and associated factors of strabismus in former preterm and full-term
      infants between 4 and 10 Years of age.
AB  - BACKGROUND: Limited data exist collating most of the associated factors for
      strabismus in one analysis. The aim of this study was to assess the prevalence of
      strabismus and to analyse associated factors in former preterm and full-term
      infants. METHODS: In this cross-sectional study, 239 former preterm infants with
      gestational age (GA) <= 32 weeks and 264 former full-term born infants with GA >=
      37 weeks underwent detailed ophthalmologic examination in the age of 4-10 years
      and perinatal data assessment for risk factor analysis. Ophthalmologic
      examinations included cover testing, best corrected visual acuity, cycloplegic
      objective refraction, slit lamp as well as fundus examinations. For association
      analysis with strabismus, the following data was collected and included in
      multivariable analysis: sex, age at examination, anisometropia, myopic and
      hyperopic refractive error (>= 3 dioptres), astigmatism, birth weight percentile,
      gestational age, retinopathy of prematurity occurrence, maternal age at
      childbirth, mother smoking, breastfeeding < 3 months, artificial ventilation,
      intraventricular bleeding, and other perinatal adverse events. RESULTS: Overall,
      4/264 (2%) full-term infants, 15/125 (12%) preterm-infants with GA 29-32 weeks
      without ROP, 13/59 (22%) preterm infants with GA <= 28 weeks without ROP and
      14/55 (26%) with GA <= 32 weeks with retinopathy of prematurity were affected by
      strabismus. In the multivariable regression model strabismus was associated with
      GA (OR = 0.84 per week; p = 0.001), hyperopic refractive error (OR = 4.22; p =
      0.002) and astigmatism (OR = 1.68; p = 0.02). CONCLUSION: This investigation
      highlights that low gestational age and refraction of the eye are independent
      risk factors for strabismus, while the other factors show less independent
      influence.

PMID- 29197375
TI  - Life satisfaction and longitudinal changes in physical activity, diabetes and
      obesity among patients with cardiovascular diseases.
AB  - BACKGROUND: Patients with cardiovascular disease who underwent coronary
      angiography at the National Institute of Cardiac Surgery and Cardiological
      Intervention (INCCI) in Luxembourg were surveyed for cardiovascular risk factors
      (CVRF) (hypertension, hypercholesterolemia, diabetes, obesity, physical
      inactivity, tobacco consumption). In 2013/14, their life satisfaction (LS) was
      also assessed. Our aim was to analyse the relationships between LS on one hand
      and longitudinal changes in CVRF between 2008/09 and 2013/14 and socioeconomic
      factors on the other. METHODS: 1289 patients completed a self-administered
      questionnaire. Life Satisfaction, originally recorded on a 1 to 10 scale of
      complete satisfaction was dichotomized into two groups: <= 7 and. >7. We then
      performed logistic multiple regressions. The event on which the probability was
      modelled, was LS > 7. Data were adjusted on age, sex and income. Longitudinal
      changes in CVRF were assessed by their presence or absence in 2008/09 and 2013/14
      (categories: 'no-no'; 'no-yes'; 'yes-no'; 'yes-yes'). RESULTS: Physical activity
      in 2008/09 and 2013/14 was associated with a lower LS (OR = 0.469). The same
      pattern was observed for obesity and physical inactivity: lower LS was related to
      the presence of these risks (yes-yes; no-yes) in 2013/14 (mean OR for obesity and
      physical inactivity in 2013/14: 0.587 and 0.485 respectively), whereas their
      presence or absence in 2008/09 was not related to LS. Finally, patients who
      suffered from diabetes in 2008 were more likely to experience a decline in LS,
      particularly if their diabetes was less severe in 2013/14 (OR = 0.462).
      CONCLUSIONS: The lowest LS was observed when obesity or physical inactivity was
      present in 2013/14, newly or otherwise. The same trend was seen in diabetes among
      patients who had it in 2008/9, but were less severely affected in 2013/14. In
      secondary prevention, CVD-related upheavals could be minimised if professionals
      and patients became 'Partners in Healthcare' to better adhere to healthy
      lifestyles, as well as to reduce CVRF, and thereby enhance LS.

PMID- 29197376
TI  - Development and testing of the KERNset: an instrument to assess the quality of
      telephone triage in out-of-hours primary care services.
AB  - BACKGROUND: Telephone triage is a core but vulnerable part of the care process at
      out-of-hours general practitioner (GP) cooperatives. In the Netherlands,
      different instruments have been used for assessing the quality of telephone
      triage. These instruments focussed mainly on communicational aspects, and less on
      the medical quality of triage decisions. Our aim was to develop and test a
      minimum set of items to assess the quality of telephone triage. METHODS: A
      national survey among all GP cooperatives in the Netherlands was performed to
      examine the most important aspects of telephone triage. Next, corresponding items
      from existing instruments were searched on these topics. Subsequently, an expert
      panel judged these items on importance, completeness and formulation. The concept
      KERNset consisted of 24 items about the telephone conversation: 13 medical, ten
      communicational and one regarding both types. It was pilot tested on measurement
      characteristics, reliability, validity and variation between triagists. In this
      pilot study, 114 anonymous calls from four GP cooperatives spread across the
      Netherlands were judged by three out of eight raters, both internal and external
      raters. RESULTS: Cronbach's alpha was .94 for the medical items and .75 for the
      communicational items. Inter-rater reliability: complete agreement between the
      external raters was 45% and reasonable agreement 73% (difference of maximally one
      point on the five-point scale). Intra-rater reliability: complete agreement
      within raters was 55% and reasonable agreement 84%. There were hardly any
      differences between internal and external raters, but there were differences in
      strictness between individual raters. The construct validity was confirmed by the
      high correlation between the general impression of the call and the items of the
      KERNset. Of the differences within items 19% could be explained by differences
      between triage nurses, which means the KERNset is able to demonstrate differences
      between triage nurses. CONCLUSIONS: The KERNset can be used to assess the quality
      of telephone triage. The validity is good and differences between calls and
      between triage nurses can be measured. A more intensive training for raters could
      improve the reliability.

PMID- 29197377
TI  - Regulation of TERRA on telomeric and mitochondrial functions in IPF pathogenesis.
AB  - BACKGROUND: Aging is a known risk factor of idiopathic pulmonary fibrosis (IPF).
      However, the pathogenic mechanisms underlying the effects of advanced aging
      remain largely unknown. Telomeric repeat-containing RNA (TERRA) represents a type
      of long noncoding RNA. In this study, the regulatory roles of TERRA on human
      telomeres and mitochondria and IPF epithelial injury model were identified.
      METHODS: Blood samples were collected from patients with IPF (n = 24) and matched
      control individuals (n = 24). The significance of clinical research on the TERRA
      expression correlated with pulmonary fibrosis was assessed. The expression levels
      of TERRA in vivo and in vitro were determined through quantitative real-time
      polymerase chain reaction analysis. Telomerase activity was observed using a
      fluorescent quantitative TRAP assay kit. The functions of telomeres,
      mitochondria, and associated genes were analyzed through RNA interference on
      TERRA. RESULTS: TERRA expression levels significantly increased in the peripheral
      blood mononuclear cells of IPF patients. The expression levels also exhibited a
      direct and significantly inverse correlation with the percentage of predicted
      force vital capacity, which is a physiological indicator of fibrogenesis during
      IPF progression. This finding was confirmed in the epithelial injury model of IPF
      in vitro. RNA interference on TERRA expression can ameliorate the functions of
      telomeres; mitochondria; associated genes; components associated with telomeres,
      such as telomerase reverse transcriptase, telomerase, and cell nuclear antigen,
      cyclin D1; and mitochondria-associated cyclin E genes, including the MMP and Bcl
      2 family. The RNA interference on TERRA expression can also improve the functions
      of oxidative-stress-associated genes, such as reactive oxygen species, superoxide
      dismutase, and catalase, and apoptosis-related genes, such as cytochrome c,
      caspase-9, and caspase-3. CONCLUSIONS: In this study, the regulation of TERRA
      expression on telomeres and mitochondria during IPF pathogenesis was identified
      for the first time. The results may provide valuable insights for the discovery
      of a novel biomarker or therapeutic approach for IPF treatment.

PMID- 29197378
TI  - Informed consent for clinical treatment in low-income setting: evaluating the
      relationship between satisfying consent and extent of recall of consent
      information.
AB  - BACKGROUND: Treatment informed consent aims to preserve the autonomy of patients
      in the clinician - patient relationship so as to ensure valid consent. An
      acceptable method of evaluating understanding of consent information is by
      assessing the extent of recall by patients of the pieces information believed to
      have been passed across. When concerns are not satisfactorily addressed from the
      patients' perspective, recall of consent information may be low. METHODS: This
      study is a questionnaire - based cross - sectional interview of consecutive adult
      surgical patients who could give their respective medical histories and who were
      booked for elective major surgical procedures over a period of 7 months in a
      tertiary health institution in southeastern Nigeria. Four to five days after a
      formal consent session, during ward admission, extent of recall of information on
      the nature of the disease condition or diagnosis, the nature of the planned
      procedure and the risks involved in the planned procedure were assessed and
      analyzed on the background of how satisfying the consent sessions were from
      individual patient's perspective. RESULTS: Generally, the recall of nature of
      disease condition and nature of planned procedure is better than recall of risks
      involved in the planned procedure. More specifically however, recall in these 3
      domains is significantly better among the patients that affirmed that their
      concerns were satisfactorily addressed. CONCLUSION: The findings from this study
      support that no effort should be spared in ensuring that the consent information
      are satisfying to the patients from the patients' viewpoint.

PMID- 29197380
TI  - A time-course microarray data analysis reveals consistent dysregulated genes and
      upstream microRNAs in autoantibody-mediated arthritis.
AB  - BACKGROUND: The purpose of this study is to identify key genes and microRNAs
      (miRNAs) involved in autoantibody-mediated arthritis (AMA). METHODS: A time
      course microarray data (ID: GSE27492) of peripheral blood leukocytes, ankle
      tissue, and synovial fluid from K/BxN mouse serum-transferred mice were
      downloaded from Gene Expression Omnibus. Those samples were collected at days 0,
      1, 3, 7, 12, and 18 after serum injection. Limma of R was employed to identify
      differentially expressed genes (DEGs) in samples collected at days 1-18 compared
      with those collected at day 0. Consistent DEGs were obtained by taking the
      interaction of DEGs from different time points, followed by functional enrichment
      analysis. MiRNAs were screened out and constructed into regulatory network with
      DEGs using Cytoscape. RESULTS: In total, 17 consistent DEGs were obtained,
      including downregulated Ephx1 and upregulated AF251705, Adam8, Arg1, Basp1, Ccl2,
      Ccl7, Ccl9, Ccr2, Clec4a2, Clec4d, Cxcl1, Fabp5, Fcgr1, Gp49a, Il1rn, and Saa3.
      Those DEGs were associated with biological processes of immune response,
      inflammatory response, and defense response; chemokine signaling pathway;
      cytokine-cytokine receptor interaction; and NOD-like receptor signaling pathway.
      Additionally, 202 miRNAs were identified to have a regulatory effect on 9 of the
      17 DEGs. Notably, miR-944, miR-374a, and miR374b were found to regulate the
      expression of Cxcl1, Ccl7, and Ccl2. Clec4d was targeted by 78 miRNAs.
      CONCLUSIONS: Our study reveals that 17 DEGs and 202 miRNAs may be associated with
      autoimmune disorder in the progression of AMA, which could guide future
      researches.

PMID- 29197381
TI  - Cross-cultural validation and psychometric testing of the Norwegian version of
      the TeamSTEPPS(r) teamwork perceptions questionnaire.
AB  - BACKGROUND: Teamwork is an integrated part of today's specialized and complex
      healthcare and essential to patient safety, and is considered as a core
      competency to improve twenty-first century healthcare. Teamwork measurements and
      evaluations show promising results to promote good team performance, and are
      recommended for identifying areas for improvement. The validated TeamSTEPPS(r)
      Teamwork Perception Questionnaire (T-TPQ) was found suitable for cross-cultural
      validation and testing in a Norwegian context. T-TPQ is a self-report survey that
      examines five dimensions of perception of teamwork within healthcare settings.
      The aim of the study was to translate and cross-validate the T-TPQ into
      Norwegian, and test the questionnaire for psychometric properties among
      healthcare personnel. METHODS: The T-TPQ was translated and adapted to a
      Norwegian context according to a model of a back-translation process. A total of
      247 healthcare personnel representing different professionals and hospital
      settings responded to the questionnaire. A confirmatory factor analysis was
      carried out to test the factor structure. Cronbach's alpha was used to establish
      internal consistency, and an Intraclass Correlation Coefficient was used to
      assess the test - retest reliability. RESULT: A confirmatory factor analysis
      showed an acceptable fitting model (chi2 (df) 969.46 (546), p < 0.001, Root Mean
      Square Error of Approximation (RMSEA) = 0.056, Tucker-Lewis Index (TLI) = 0.88,
      Comparative fit index (CFI) = 0.89, which indicates that each set of the items
      that was supposed to accompany each teamwork dimension clearly represents that
      specific construct. The Cronbach's alpha demonstrated acceptable values on the
      five subscales (0.786-0.844), and test-retest showed a reliability parameter,
      with Intraclass Correlation Coefficient scores from 0.672 to 0.852. CONCLUSION:
      The Norwegian version of T-TPQ was considered to be acceptable regarding the
      validity and reliability for measuring Norwegian individual healthcare
      personnel's perception of group level teamwork within their unit. However, it
      needs to be further tested, preferably in a larger sample and in different
      clinical settings.

PMID- 29197379
TI  - Factors involved in cancer metastasis: a better understanding to "seed and soil"
      hypothesis.
AB  - Metastasis has intrigued researchers for more than 100 years. Despite the
      development of technologies and therapeutic strategies, metastasis is still the
      major cause of cancer-related death until today. The famous "seed and soil"
      hypothesis is widely cited and accepted, and it still provides significant
      instructions in cancer research until today. To our knowledge, there are few
      reviews that comprehensively and correlatively focus on both the seed and soil
      factors involved in cancer metastasis; moreover, despite the fact that
      increasingly underlying mechanisms and concepts have been defined recently,
      previous perspectives are appealing but may be limited. Hence, we reviewed
      factors involved in cancer metastasis, including both seed and soil factors. By
      integrating new concepts with the classic hypothesis, we aim to provide a
      comprehensive understanding of the "seed and soil" hypothesis and to
      conceptualize the framework for understanding factors involved in cancer
      metastasis. Based on a dynamic overview of this field, we also discuss potential
      implications for future research and clinical therapeutic strategies.

PMID- 29197382
TI  - Beyond quality improvement: exploring why primary care teams engage in a
      voluntary audit and feedback program.
AB  - BACKGROUND: Despite its popularity, the effectiveness of audit and feedback in
      support quality improvement efforts is mixed. While audit and feedback-related
      research efforts have investigated issues relating to feedback design and
      delivery, little attention has been directed towards factors which motivate
      interest and engagement with feedback interventions. This study explored the
      motivating factors that drove primary care teams to participate in a voluntary
      audit and feedback initiative. METHODS: Interviews were conducted with leaders of
      primary care teams who had participated in at least one iteration of the audit
      and feedback program. This intervention was developed by an organization which
      advocates for high-quality, team-based primary care in Ontario, Canada. Interview
      transcripts were coded using the Consolidated Framework for Implementation
      Research and the resulting framework was analyzed inductively to generate key
      themes. RESULTS: Interviews were completed with 25 individuals from 18 primary
      care teams across Ontario. The majority were Executive Directors (14), Physician
      leaders (3) and support staff for Quality Improvement (4). A range of motivations
      for participating in the audit and feedback program beyond quality improvement
      were emphasized. Primarily, informants believed that the program would eventually
      become a best-in-class audit and feedback initiative. This reflected concerns
      regarding existing initiatives in terms of the intervention components and
      intentions as well as the perception that an initiative by primary care, for
      primary care would better reflect their own goals and better support desired
      patient outcomes. Key enablers included perceived obligations to engage and
      provision of support for the work involved. No teams cited an evidence base for
      A&F as a motivating factor for participation. CONCLUSIONS: A range of motivating
      factors, beyond quality improvement, contributed to participation in the audit
      and feedback program. Findings from this study highlight that efforts to
      understand how and when the intervention works best cannot be limited to factors
      within developers' control. Clinical teams may more readily engage with
      initiatives with the potential to address their own long-term system goals.
      Aligning motivations for participation with the goals of the audit and feedback
      initiative may facilitate both engagement and impact.

PMID- 29197383
TI  - Analysis of population-level determinants of legionellosis: spatial and geovisual
      methods for enhancing classification of high-risk areas.
AB  - BACKGROUND: Although the incidence of legionellosis throughout North America and
      Europe continues to increase, public health investigations have not been able to
      identify a common exposure in most cases. Over 80% of cases are sporadic with no
      known source. To better understand the role of the macro-environment in
      legionellosis risk, a retrospective ecological study assessed associations
      between population-level measures of demographic, socioeconomic, and
      environmental factors and high-risk areas. METHODS: Geographic variability and
      clustering of legionellosis was explored in our study setting using the following
      methods: unadjusted and standardized incidence rate and SaTScanTM cluster
      detection methods using default scanning window of 1 and 50% as well as a
      reliability score methodology. Methods for classification of "high-risk" census
      tracts (areas roughly equivalent to a neighborhood with average population of
      4000) for each of the spatial methods are presented. Univariate and multivariate
      logistic regression analyses were used to estimate associations with
      sociodemographic factors: population >= 65 years of age, non-white race, Hispanic
      ethnicity, poverty, less than or some high school education; housing factors:
      housing vacant, renter-occupied, and built pre-1950 and pre-1970; and whether
      drinking water is groundwater or surface water source. RESULTS: Census tracts
      with high percentages of poverty, Hispanic population, and non-white population
      were more likely to be classified as high-risk for legionellosis versus a low
      risk census tract. Vacant housing, renter-occupied housing, and homes built pre
      1970 were also important positively associated risk factors. Drinking water
      source was not found to be associated with legionellosis incidence. DISCUSSION:
      Census tract level demographic, socioeconomic, and environmental characteristics
      are important risk factors of legionellosis and add to our understanding of the
      macro-environment for legionellosis occurrence. Our findings can be used by
      public health professionals to target disease prevention communication to
      vulnerable populations. Future studies are needed to explore the exact mechanisms
      by which these risk factors may influence legionellosis clustering.

PMID- 29197384
TI  - Involvement of the bone morphogenic protein/SMAD signaling pathway in the
      etiology of congenital anomalies of the kidney and urinary tract accompanied by
      cryptorchidism.
AB  - BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as
      renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common
      causes of end-stage renal disease. However, the genetic etiology of CAKUT remains
      unclear. In this study, we performed whole exome sequencing (WES) to elucidate
      the genetic etiology of symptomatic CAKUT and CAKUT accompanied by
      cryptorchidism. METHODS: Three patients with unilateral renal dysplasia
      accompanied by ipsilateral cryptorchidism were included in this analysis. Genomic
      DNA was extracted from peripheral blood, and WES was performed. Disease-specific
      single nucleotide polymorphisms (SNPs) were determined by comparison with the
      human genome reference sequence (hg19). Additionally, we searched for SNPs that
      were common to all three patients, with a particular focus on the coding regions
      of the target genes. RESULTS: In total, 8710 SNPs were detected. Of the genes
      harboring these SNPs, 32 associated with renal or testicular development were
      selected for further analyses. Of these, eight genes (i.e., SMAD4, ITGA8, GRIP1,
      FREM1, FREM2, TNXB, BMP8B, and SALL1) carried a single amino acid substitution
      that was common to all three patients. In particular, SNPs in SMAD4 (His290Pro
      and His291Pro) have not been reported previously in patients with symptomatic
      CAKUT. Of the candidate genes, four genes (i.e., ITGA8, GRIP1, FREM1, and FREM2)
      were Fraser syndrome-related genes, encoding proteins that functionally converged
      on the glial cell-derived neurotrophic factor/RET/bone morphogenic protein (BMP)
      signaling pathways. As another candidate gene, the protein encoded by BMP8B
      activates the nuclear translocation of SMAD4, which regulates the expression of
      genes associated with the differentiation of primordial germ cells or testicular
      development. Additionally, BMP4, a member of the BMP family, regulates the
      interaction between metanephric mesenchyme and ureteric buds by suppressing GDNF.
      CONCLUSIONS: Taken together, our findings suggested that the development of the
      kidney and urinary tract is intimately linked with that of male reproductive
      organs via BMP/SMAD signaling pathways.

PMID- 29197385
TI  - Qualitative evaluation of trauma delays in road traffic injury patients in
      Maringa, Brazil.
AB  - BACKGROUND: Road traffic injuries (RTIs) are the eighth leading cause of death
      worldwide, with an estimated 90% of RTIs occurring in low- and middle-income
      countries (LMICs) like Brazil. There has been minimal research in evaluation of
      delays in transport of RTI patients to trauma centers in LMICs. The objective of
      this study is to determine specific causes of delays in prehospital transport of
      road traffic injury patients to designated trauma centers in Maringa, Brazil.
      METHODS: A qualitative method was used based on the Consolidated Criteria for
      Reporting Qualitative Research (COREQ) approach. Eleven health care providers
      employed at prehospital or hospital settings were interviewed with questions
      specific to delays in care for RTI patients. A thematic analysis was conducted.
      RESULTS: Responses to primary causes of delay in treatment to RTI patients fell
      into the following categories: 1) lack of public education, 2) traffic, 3)
      insufficient personnel/ambulances, 4) bureaucracy, and 5) poor location of
      stations. Suggestions for improvement in delays fell into the categories of 1)
      need for centralized station/avoid traffic, 2) improving public education, 3)
      Increase personnel, 4) increase ambulances, 5) proper extrication/rapid
      treatment. CONCLUSION: Our study found varied responses between hospital and SAMU
      providers regarding specific causes of delay for RTI patients; SAMU providers
      cited primarily traffic, bureaucracy, and poor location as primary factors while
      hospital employees focused more on public health aspects. These results mirror
      prehospital system challenges in other developing countries, but also provide
      solutions for improvement with better infrastructure and public health campaigns.

PMID- 29197386
TI  - Cost analysis of two community-based HIV testing service modalities led by a Non
      Governmental Organization in Cape Town, South Africa.
AB  - BACKGROUND: In South Africa, the financing and sustainability of HIV services is
      a priority. Community-based HIV testing services (CB-HTS) play a vital role in
      diagnosis and linkage to HIV care for those least likely to utilise government
      health services. With insufficient estimates of the costs associated with CB-HTS
      provided by NGOs in South Africa, this cost analysis explored the cost to
      implement and provide services at two NGO-led CB-HTS modalities and calculated
      the costs associated with realizing key HIV outputs for each CB-HTS modality.
      METHODS: The study took place in a peri-urban area where CB-HTS were provided
      from a stand-alone centre and mobile service. Using a service provider (NGO)
      perspective, all inputs were allocated by HTS modality with shared costs
      apportioned according to client volume or personnel time. We calculated the total
      cost of each HTS modality and the cost categories (personnel, capital and
      recurring goods/services) across each HTS modality. Costs were divided into seven
      pre-determined project components, used to examine cost drivers. HIV outputs were
      analysed for each HTS modality and the mean cost for each HIV output was
      calculated per HTS modality. RESULTS: The annual cost of the stand-alone and
      mobile modalities was $96,616 and $77,764 respectively, with personnel costs
      accounting for 54% of the total costs at the stand-alone. For project components,
      overheads and service provision made up the majority of the costs. The mean cost
      per person tested at stand-alone ($51) was higher than at the mobile ($25).
      Linkage to care cost at the stand-alone ($1039) was lower than the mobile
      ($2102). CONCLUSIONS: This study provides insight into the cost of an NGO led CB
      HTS project providing HIV testing and linkage to care through two CB-HIV testing
      modalities. The study highlights; (1) the importance of including all applicable
      costs (including overheads) to ensure an accurate cost estimate that is
      representative of the full service implementation cost, (2) the direct link
      between test uptake and mean cost per person tested, and (3) the need for
      effective linkage to care strategies to increase linkage and thereby reduce the
      mean cost per person linked to HIV care.

PMID- 29197387
TI  - Liraglutide and Metformin alone or combined therapy for type 2 diabetes patients
      complicated with coronary artery disease.
AB  - BACKGROUND: This study is to compare the effects of Liraglutide and Metformin
      alone or combined treatment on the cardiac function in T2DM patients complicated
      with CAD. METHODS: 120 T2DM patients were included at Endocrinology Department of
      Tianjin First Center Hospital (Tianjin, China) from April 2012 to September 2013.
      The study contained two sections. Section 1: 30 patients in group 1 was treated
      with Liraglutide (Novo Nordisk) (1.2 mg/d), and 30 patients in group 2 with
      Metformin (Shiguibao) (1500 mg/d) for 24 weeks. Section 2: 30 patients in group1
      was treated with Liraglutide (1.8 mg/d) and 30 in group 2 with Liraglutide (1.2
      mg/d) plus Metformin (1500 mg/d) for 24 weeks. Fasting blood glucose (FBG),
      postprandial glucose (PPG), glycated hemoglobin (HbA1c), body mass index (BMI),
      blood pressure (BP), triglyceride (TG), total cholesterol (TC), low-density
      lipoprotein cholesterol (LDL-C), C reactive protein (CRP), left ventricular end
      diastolic diameter (LVEDD), ejection fraction (EF) and the ratio of early (E) to
      late (A) ventricular filling velocities (E/A ratio) were measured before and
      after the 24-week treatment. RESULTS: After 24-week treatment, when blood glucose
      level was controlled in 4 groups, Liraglutide alone treatment showed better
      improvements than on all measuring except TG in Section 1, however, combined
      treatment of Liraglutide and Metformin showed better improvements on all
      measuring except BMI, TG and BP in Section 2. CONCLUSIONS: With similar glycemic
      control, the Liraglutide (1.2 mg/d) monotherapy showed the better effects than
      either Metformin alone, or combination of Liraglutide and Metformin on lipid
      metabolism and cardiovascular function. TRIAL REGISTRATION: This trial was
      registered at Chinese Clinical Trial Registry ( chictr.org.cn ) # ChiCTR-IPR
      16008578 .

PMID- 29197388
TI  - Spontaneous hemothorax caused by ruptured multiple mycotic aortic aneurysms: a
      case report and literature review.
AB  - BACKGROUND: Mycotic aortic aneurysm (MAA) is a rare clinical entity with an
      incidence of 1-3%, but it is a life-threatening infection of aorta characterized
      by dilatation of aorta with false lumen. Multiple MAAs have been reported rarely
      with an incidence of 0.03% and associated with a high mortality rate of 80% if
      ruptured. CASE PRESENTATION: A hypertensive and diabetic 78-year-old man visited
      our emergency department complaining intermittent dull and tingled pain over the
      left flank region for 1 week. Chest X-ray showed left pleural effusion and
      hemothorax was confirmed by thoracocentesis. Computed tomography (CT) of chest
      demonstrated multiple thoracic aortic aneurysms and the pathological findings
      disclosed the diagnosis of multiple MAAs. He was discharged under an uneventful
      condition post-surgical aortic repair with adequate intravenous antibiotics for 4
      weeks. CONCLUSIONS: CT scan may make a definite diagnosis of multiple MAAs and
      management with surgical debridement, aortic repair and full-course antibiotics
      for Gram-positive coccus and/or Gram-negative bacillus is recommended.

PMID- 29197389
TI  - Foamy virus zoonotic infections.
AB  - BACKGROUND: Foamy viruses (FV) are ancient complex retroviruses that differ from
      orthoretroviruses such as human immunodeficiency virus (HIV) and murine leukemia
      virus (MLV) and comprise a distinct subfamily of retroviruses, the
      Spumaretrovirinae. FV are ubiquitous in their natural hosts, which include cows,
      cats, and nonhuman primates (NHP). FV are transmitted mainly through saliva and
      appear nonpathogenic by themselves, but they may increase morbidity of other
      pathogens in coinfections. CONCLUSIONS: This review summarizes and discusses what
      is known about FV infection of natural hosts. It also emphasizes what is known
      about FV zoonotic infections A large number of studies have revealed that the FV
      of NHP, simian foamy viruses (SFV), are transmitted to humans who interact with
      infected NHP. SFV from a variety of NHP establish persistent infection in humans,
      while bovine foamy virus and feline foamy virus rarely or never do. The
      possibility of FV recombination and mutation leading to pathogenesis is
      considered. Since humans can be infected by SFV, a seemingly nonpathogenic virus,
      there is interest in using SFV vectors for human gene therapy. In this regard,
      detailed understanding of zoonotic SFV infection is highly relevant.

PMID- 29197390
TI  - Evaluation of B1 inhomogeneity effect on DCE-MRI data analysis of brain tumor
      patients at 3T.
AB  - BACKGROUND: Dynamic-contrast-enhanced (DCE) MRI data acquired using gradient echo
      based sequences is affected by errors in flip angle (FA) due to transmit B1
      inhomogeneity (B1inh). The purpose of the study was to evaluate the effect of
      B1inh on quantitative analysis of DCE-MRI data of human brain tumor patients and
      to evaluate the clinical significance of B1inh correction of perfusion parameters
      (PPs) on tumor grading. METHODS: An MRI study was conducted on 35 glioma patients
      at 3T. The patients had histologically confirmed glioma with 23 high-grade (HG)
      and 12 low-grade (LG). Data for B1-mapping, T1-mapping and DCE-MRI were acquired.
      Relative B1 maps (B1rel) were generated using the saturated-double-angle method.
      T1-maps were computed using the variable flip-angle method. Post-processing was
      performed for conversion of signal-intensity time (S(t)) curve to concentration
      time (C(t)) curve followed by tracer kinetic analysis (Ktrans, Ve, Vp, Kep) and
      first pass analysis (CBV, CBF) using the general tracer-kinetic model. DCE-MRI
      data was analyzed without and with B1inh correction and errors in PPs were
      computed. Receiver-operating-characteristic (ROC) analysis was performed on HG
      and LG patients. Simulations were carried out to understand the effect of B1
      inhomogeneity on DCE-MRI data analysis in a systematic way. S(t) curves mimicking
      those in tumor tissue, were generated and FA errors were introduced followed by
      error analysis of PPs. Dependence of FA-based errors on the concentration of
      contrast agent and on the duration of DCE-MRI data was also studied. Simulations
      were also done to obtain Ktrans of glioma patients at different B1rel values and
      see whether grading is affected or not. RESULTS: Current study shows that B1rel
      value higher than nominal results in an overestimation of C(t) curves as well as
      derived PPs and vice versa. Moreover, at same B1rel values, errors were large for
      larger values of C(t). Simulation results showed that grade of patients can
      change because of B1inh. CONCLUSIONS: B1inh in the human brain at 3T-MRI can
      introduce substantial errors in PPs derived from DCE-MRI data that might affect
      the accuracy of tumor grading, particularly for border zone cases. These errors
      can be mitigated using B1inh correction during DCE-MRI data analysis.

PMID- 29197391
TI  - Exploring the feasibility of eHealth solutions to decrease delays in maternal
      healthcare in remote communities of Ghana.
AB  - BACKGROUND: Despite the introduction of the Millennium Development Goal to reduce
      maternal deaths from 400 to 100 per 100,000 live births, the proportion of
      maternal deaths is still much higher in most developing countries like Ghana.
      Various interventions have been implemented in Ghana that focus on increasing
      skilled maternal care. These are especially needed in rural areas. EHealth has
      the potential to contribute to reducing the challenges in maternal healthcare
      (MHC) that poor areas suffer. This paper analyzes the potential of eHealth
      solutions to improve maternal health in rural Ghana as well as the challenges to
      their implementation. The work was carried out in cooperation with the local
      health directorate of Kpando Municipality, one of the administrative areas in the
      Volta Region. METHODS: The study is focused on remote peninsulas and islands in
      Kpando Municipality. Data was gathered through triangulated research methods.
      Maternal health challenges were identified using the Three Delays Model for MHC.
      The three delays are delay in seeking care, delay accessing health facilities,
      and delay receiving adequate care. Challenges to the implementation of eHealth
      solutions in remote communities were analyzed using the Drury's 5C eHealth model
      for developing countries. The 5Cs correspond to context, community, capacity,
      connectivity, and content. RESULTS: The results show that financial dependence of
      women, a decision-making process based on previous experiences and traditional
      beliefs, competitiveness between facilities, organizational loopholes, lack of
      equipment, and geographical situations directly influence MHC outcomes. EHealth
      solutions, thanks to the high number of health workers with basic IT skills, have
      high potential to reduce MHC delays. However, poverty, cultural beliefs,
      organizational issues, connectivity, and lack of human resources were identified
      as main challenges to the implementation of eHealth solutions. CONCLUSION: In
      Ghana's rural areas the three delays proposed in the model affect the outcomes of
      MHC. These delays are influenced by socio-economic status, access to facilities,
      and quality of care. EHealth solutions show great potential to reduce the delays.
      Based on the 5C model, a mHealth solution aiming to improve guidance during
      pregnancy was outlined.

PMID- 29197392
TI  - Genetic toggle switch controlled by bacterial growth rate.
AB  - BACKGROUND: In favorable conditions bacterial doubling time is less than 20 min,
      shorter than DNA replication time. In E. coli a single round of genome
      replication lasts about 40 min and it must be accomplished about 20 min before
      cell division. To achieve such fast growth rates bacteria perform multiple
      replication rounds simultaneously. As a result, when the division time is as
      short as 20 min E. coli has about 8 copies of origin of replication (ori) and the
      average copy number of the genes situated close to ori can be 4 times larger than
      those near the terminus of replication (ter). It implies that shortening of cell
      cycle may influence dynamics of regulatory pathways involving genes placed at
      distant loci. RESULTS: We analyze this effect in a model of a genetic toggle
      switch, i.e. a system of two mutually repressing genes, one localized in the
      vicinity of ori and the other localized in the vicinity of ter. Using a
      stochastic model that accounts for cell growth and divisions we demonstrate that
      shortening of the cell cycle can induce switching of the toggle to the state in
      which expression of the gene placed near ter is suppressed. The toggle
      bistability causes that the ratio of expression of the competing genes changes
      more than two orders of magnitude for a two-fold change of the doubling time. The
      increasing stability of the two toggle states enhances system sensitivity but
      also its reaction time. CONCLUSIONS: By fusing the competing genes with
      fluorescent tags this mechanism could be tested and employed to create an
      indicator of the doubling time. By manipulating copy numbers of the competing
      genes and locus of the gene situated near ter, one can obtain equal average
      expression of both genes for any doubling time T between 20 and 120 min. Such a
      toggle would accurately report departures of the doubling time from T.

PMID- 29197393
TI  - Association of serum ferritin with non-alcoholic fatty liver disease: a meta
      analysis.
AB  - BACKGROUND: A growing number of studies reported the connection between the level
      of serum ferritin (SFL) and non-alcoholic fatty liver disease (NAFLD). However,
      such connection was still disputable. The aim of our meta-analysis was to
      estimate SFL between the groups as below: patients with NAFLD against control
      group; non-alcoholic steatohepatitis (NASH) patients against control group; non
      alcoholic fatty liver (NAFL) patients against a control group and NASH patients
      vs NAFL patients. METHODS: We screened the studies in PubMed, EMBASE, the
      Cochrane Database and the Cochrane Central register controlled trials from the
      beginning to July 10, 2016 to find the studies indicated the connection between
      SFL and NAFLD (NAFL and/or NASH). Fourteen published studies which evaluate the
      SFL in NAFLD patients were selected. RESULTS: Higher SFL was noticed in NAFLD
      patients against control group (standardized mean difference [SMD] 1.01; 95% CI
      0.89, 1.13), NASH patients against control group (SMD 1.21; 95% CI 1.00, 1.42),
      NAFL patients against control group (SMD 0.51; 95% CI 0.24, 0.79) and NASH
      patients against NAFL patients (SMD 0.63; 95% CI 0.52, 0.75). These results
      remained unaltered actually after the elimination of studies which were focused
      on paediatric or adolescent populations. Higher SFL was presented in NAFLD
      patients against the control group (SMD 1.08; 95% CI 0.95, 1.20) in adults and
      NASH patients against NAFL patients in adults (SMD 0.74; 95% CI 0.62, 0.87). The
      connection between SFL and NASH against NAFL group in paediatric or adolescent
      populations was observed inconsistently (SMD 0.10; 95% CI -0.18, 0.38).
      CONCLUSIONS: The level of SFL was elevated in patients with NAFLD (NAFL and/or
      NASH) compared with the controls. Compared with NAFL, The level of SFL was
      increased in NASH. The result remained unaltered actually after the elimination
      of studies focused on paediatric or adolescent populations.

PMID- 29197394
TI  - Designing synthetic networks in silico: a generalised evolutionary algorithm
      approach.
AB  - BACKGROUND: Evolution has led to the development of biological networks that are
      shaped by environmental signals. Elucidating, understanding and then
      reconstructing important network motifs is one of the principal aims of Systems &
      Synthetic Biology. Consequently, previous research has focused on finding optimal
      network structures and reaction rates that respond to pulses or produce stable
      oscillations. In this work we present a generalised in silico evolutionary
      algorithm that simultaneously finds network structures and reaction rates
      (genotypes) that can satisfy multiple defined objectives (phenotypes). RESULTS:
      The key step to our approach is to translate a schema/binary-based description of
      biological networks into systems of ordinary differential equations (ODEs). The
      ODEs can then be solved numerically to provide dynamic information about an
      evolved networks functionality. Initially we benchmark algorithm performance by
      finding optimal networks that can recapitulate concentration time-series data and
      perform parameter optimisation on oscillatory dynamics of the Repressilator. We
      go on to show the utility of our algorithm by finding new designs for robust
      synthetic oscillators, and by performing multi-objective optimisation to find a
      set of oscillators and feed-forward loops that are optimal at balancing different
      system properties. In sum, our results not only confirm and build on previous
      observations but we also provide new designs of synthetic oscillators for
      experimental construction. CONCLUSIONS: In this work we have presented and tested
      an evolutionary algorithm that can design a biological network to produce desired
      output. Given that previous designs of synthetic networks have been limited to
      subregions of network- and parameter-space, the use of our evolutionary
      optimisation algorithm will enable Synthetic Biologists to construct new systems
      with the potential to display a wider range of complex responses.

PMID- 29197395
TI  - Translation and psychometric testing of the Farsi version of the Seattle angina
      questionnaire.
AB  - BACKGROUND: Angina pectoris causes substantial psychological and functional
      disabilities and adversely effects quality of life in patients. The aim of this
      study was to investigate the psychometric properties including validity and
      reliability of the Farsi version of the Seattle angina questionnaire. METHODS:
      The 'forward-backward' procedure was applied to translate this questionnaire from
      English to Farsi. The translated version of the Seattle angina questionnaire was
      assessed in terms of validity and reliability with a convenience sample of 200
      patients suffering from angina pectoris who were recruited from the inpatient
      ward (post CCU) and outpatient department at two teaching hospitals in an urban
      area of Iran. Validity was assessed using content, face and construct validity.
      The calculation of the Cronbach's alpha coefficient and the test-retest method
      helped with the assessment of reliability of the questionnaire's five subscales.
      Construct validity of the questionnaire was evaluated using exploratory factor
      analysis. RESULTS: The results of exploratory factor analysis indicated a five
      factor solution for the questionnaire including 'physical limitation in middle to
      strenuous activities', 'physical limitation in slight activities', 'angina
      pattern and discomfort of treatment', 'treatment satisfaction' and 'disease
      perception' that jointly accounted for 64.42% of variance observed. Convergent
      validity was mostly supported by the pattern of association between the Seattle
      angina questionnaire-Farsi version and the SF-36. Cronbach's alpha of the
      subscales ranged from 0.60 to 0.86 and test-retest scores ranged from 0.79 to
      0.97 indicating a good range of reliability. CONCLUSIONS: The Seattle angina
      questionnaire-Farsi version had acceptable psychometric properties. Therefore, it
      can be used to assess health-related quality of life and assess the effects of
      different medical and nursing interventions on patients' quality of life.

PMID- 29197396
TI  - New laparoscopic procedure for left-sided pancreatic cancer-artery-first approach
      laparoscopic RAMPS using 3D technique.
AB  - BACKGROUND: For left-sided pancreatic ductal adenocarcinoma (PDAC), radical
      antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach
      for tumor-free margin resection and systemic lymph node clearance. In
      pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first
      approach (or the "artery-first approach") has become the standard procedure. With
      improvements in laparoscopic instruments and techniques, some surgeons attempted
      to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left
      sided PDAC. However, owing to several technical difficulties in this procedure,
      its application remains uncommon. Moreover, the artery-first approach in L-RAMPS
      has not been reported. Here, we developed the artery-first approach L-RAMPS for
      left-sided PDAC and have presented the same in this report. CASE PRESENTATION:
      Between June 2014 and July 2015, 16 patients with left-sided PDAC were referred
      to our division for pancreatic resection. The following technique was used for
      performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After
      opening the omental bursa, only the middle segment of the pancreas was initially
      separated from both the left renal vein and the SMA. We termed this procedure as
      the "artery-first approach using a dome-shaped dorsomedial dissection (3D)
      technique." This 3D technique enabled the interruption of the entire arterial
      supply to the specimen while preserving the venous drainage through the splenic
      vein for preventing venous congestion. The technique also contributed to the
      early detection of no tumor infiltration into the SMA and the early determination
      of posterior dissection plane. After pancreatic neck transection, the splenic
      artery and vein were divided. Finally, the pancreatic tail and spleen were
      dissected in a right-to-left direction. All operations were completed without any
      intraoperative complications. The median blood loss and retrieved lymph node
      count were 75 mL and 37, respectively, which were superior to those reported by
      other previous studies on L-RAMPS. All resection margins were free of carcinoma.
      No severe postoperative complications were observed. CONCLUSIONS: The artery
      first approach L-RAMPS using 3D technique is safe and feasible to perform. The
      significance of our proposed procedure is minimal blood loss and precise
      lymphadenectomy. Therefore, this novel technique may become the preferred
      treatment for left-sided PDAC in selected cases.

PMID- 29197397
TI  - The 'heat' goes away: sexual disorders of married women with female genital
      mutilation/cutting in Kenya.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) has been implicated in
      sexual complications among women, although there is paucity of research evidence
      on sexual experiences among married women who have undergone this cultural
      practice. The aim of this study was to investigate the sexual experiences among
      married women in Mauche Ward, Nakuru County. METHODS: Quantitative and
      qualitative data collection methods were used. Quantitative data were obtained
      from 318 married women selected through multistage sampling. The women were
      categorized into: cut before marriage, cut after marriage and the uncut. A
      questionnaire was used to collect demographic information while psychometric data
      were obtained using a female sexual functioning index (FSFI) tool. The resulting
      quantitative data were analyzed using SPSS(r) Version 22. Qualitative data were
      obtained from five FGDs and two case narratives. The data were organized into
      themes, analyzed and interpreted. Ethical approval for the study was granted by
      Kenyatta National Hospital-University of Nairobi Ethics and Research Committee.
      RESULTS: The mean age of the respondents was 30.59 +/- 7.36 years. The majority
      (74.2%) had primary education and 76.1% were farmers. Age (p = 0.008), number of
      children (p = 0.035) and education (p = 0.038) were found to be associated with
      sexual functioning. The cut women reported lower sexual functioning compared to
      the uncut. ANOVA results show the reported overall sexual functioning to be
      significantly (p = 0.019) different across the three groups. Women cut after
      marriage (mean = 22.81 +/- 4.87) scored significantly lower (p = 0.056) than the
      uncut (mean = 25.35 +/- 3.56). However, in comparison to the cut before marriage
      there was no significant difference (mean = 23.99 +/- 6.63). Among the sexual
      functioning domains, lubrication (p = 0.008), orgasm (p = 0.019) and satisfaction
      (p = 0.042) were significantly different across the three groups. However,
      desire, arousal and pain were not statistically different. CONCLUSION: Generally,
      cut women had negative sexual experiences and specifically adverse changes in
      desire, arousal and satisfaction were experienced among cut after marriage. FGM/C
      mitigating strategies need to routinely provide sexual complications management
      to safeguard women's sexual right to pleasure subsequently improving their
      general well-being.

PMID- 29197399
TI  - Abortion debates in Finland and the Republic of Ireland: textual analysis of
      experiential thinking and argumentation in parliamentary and layperson
      discussions.
AB  - BACKGROUND: The ethical discussion about abortion has been polarized in Finland
      and the Republic of Ireland, two European countries with very different abortion
      legislation (liberal vs. highly restrictive). The aim of the present study was to
      analyze experiential thinking patterns and argumentative strategies in political
      and layperson debates regarding induced abortion. METHODS: The content of Finnish
      and Irish texts (n = 493), consisting of transcripts of parliamentary debates and
      online texts, such as blogs, was analyzed systematically. The texts were
      investigated for the aspects of experiential thinking, for selected argumentative
      moves and for any differences in the prevalence of these features between
      countries or between political vs. layperson debates. RESULTS: The Finnish and
      Irish discussions about induced abortion relied heavily on experiential thinking
      patterns and emotionally laden arguments instead of objective research data. This
      was evident in the very high prevalence of testimonials, narratives, loaded
      language and appeals to emotion in both political and layperson debates
      regardless of the country or the debater's position on abortion issue. Research
      data that did not support the position of the debater were relatively often
      omitted by confirmation bias. The Irish debaters appealed to popularity more
      often than the Finnish ones, while magical/religious thinking was mainly observed
      in the Finnish layperson discussion. The national history and the prevailing
      cultural and religious atmosphere of the two countries could explain these
      differences. CONCLUSIONS: The abortion debate mostly reinforces the opinions of
      one's peer group rather than convinces the opposite party to change their
      position. The stalemate and continuation of the same arguments being repeated
      could be associated with experiential thinking and emotional argumentative
      strategies in both political and layperson debates.

PMID- 29197398
TI  - Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates
      depressive-like behavior in a mouse model of chronic stress.
AB  - BACKGROUND: It has been shown that chronic stress-induced depression is
      associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic
      acetylcholine receptors (alpha7nAChRs) regulate the cholinergic anti-inflammatory
      pathway, but the role of cholinergic signaling and alpha7nAChR in chronic stress
      has not yet been examined. METHODS: In this study, we used a well-documented
      model of depression in which mice were exposed to 6 h of restraint stress for 21
      consecutive days. Components of cholinergic signaling and TLR4 signaling were
      analyzed in the hippocampus. The main targets of neuroinflammation and neuronal
      damage were also evaluated after a series of tests for depression-like behavior.
      RESULTS: Chronic restraint stress (CRS) induced alterations in components of
      central cholinergic signaling in hippocampus, including increases in choline
      acetyltransferase protein expression and decreases in nuclear STAT3 signaling.
      CRS also increased TLR4 signaling activity, interleukin-1beta, and tumor necrosis
      factor-alpha expression, microglial activation, and neuronal morphologic changes.
      Cholinergic stimulation with the alpha7nAChR agonist DMXBA significantly
      alleviated CRS-induced depressive-like behavior, neuroinflammation, and neuronal
      damage, but these effects were abolished by the selective alpha7nAChR antagonist
      alpha-bungarotoxin. Furthermore, activation of alpha7nAChRs restored the central
      cholinergic signaling function, inhibited TLR4-mediated inflammatory signaling
      and microglial activity, and increased the number of regulatory T cells in the
      hippocampus. CONCLUSIONS: These findings provide evidence that alpha7nAChR
      activation mitigates CRS-induced neuroinflammation and cell death, suggesting
      that alpha7nAChRs could be a new therapeutic target for the prevention and
      treatment of depression.

PMID- 29197400
TI  - Evaluation of the new TNM-staging system for thymic malignancies: impact on
      indication and survival.
AB  - BACKGROUND: The objective of this study is the evaluation of the Masaoka-Koga and
      the International Association for the Study of Lung Cancer (IASLC)/International
      Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system
      on clinical implementation and prognosis of thymic malignancies. METHODS: A
      retrospective study of 76 patients who underwent surgery between January 2005 and
      December 2015 for thymoma. Kaplan-Meier survival analysis was used to determine
      overall and recurrence-free survival rates. RESULTS: Indication for surgery was
      primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or
      mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga
      stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced
      stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n =
      33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher
      levels of WHO stages. Within each staging system, the survival curves differed
      significantly with the best 5-year survival in early stages I and II (91%).
      Survival for stage IV (70 to 77%) was significantly better compared to stage III
      (49 to 54%). Early stages had a significant longer recurrence-free survival (86
      to 90%) than advanced stages III and IV (55 to 56%). CONCLUSIONS: The proportion
      of patients with IASLC/ITMIG stage I increased remarkably, whereas the
      distribution in advanced stages III and IV was nearly similar. The new TNM
      staging system presents a clinically useful and applicable system, which can be
      used for indication, stage-adapted therapy, and prediction of prognosis for
      overall and recurrence-free survival.

PMID- 29197403
TI  - Setting priorities for knowledge translation of Cochrane reviews for health
      equity: Evidence for Equity.
AB  - BACKGROUND: A focus on equity in health can be seen in many global development
      goals and reports, research and international declarations. With the development
      of a relevant framework and methods, the Campbell and Cochrane Equity Methods
      Group has encouraged the application of an 'equity lens' to systematic reviews,
      and many organizations publish reviews intended to address health equity. The
      purpose of the Evidence for Equity (E4E) project was to conduct a priority
      setting exercise and apply an equity lens by developing a knowledge translation
      product comprising summaries of systematic reviews from the Cochrane Library. E4E
      translates evidence from systematic reviews into 'friendly front end' summaries
      for policy makers. METHODS: The following topic areas with high burdens of
      disease globally, were selected for the pilot: diabetes/obesity, HIV/AIDS,
      malaria, nutrition, and mental health/depression. For each topic area, a
      "stakeholder panel" was assembled that included policymakers and researchers. A
      systematic search of Cochrane reviews was conducted for each area to identify
      equity-relevant interventions with a meaningful impact. Panel chairs developed a
      rating sheet which was used by all panels to rank the importance of these
      interventions by: 1) Ease of Implementation; 2) Health System Requirements;
      3)Universality/Generalizability/Share of Burden; and 4) Impact on
      Inequities/Effect on equity. The ratings of panel members were averaged for each
      intervention and criterion, and interventions were ordered according to the
      average overall ratings. RESULTS: Stakeholder panels identified the top 10
      interventions from their respective topic areas. The evidence on these
      interventions is being summarized with an equity focus and the results posted
      online, at http://methods.cochrane.org/equity/e4e-series . CONCLUSIONS: This
      method provides an explicit approach to setting priorities by systematic review
      groups and funders for providing decision makers with evidence for the most
      important equity-relevant interventions.

PMID- 29197402
TI  - Manual physical balance assistance of therapists during gait training of stroke
      survivors: characteristics and predicting the timing.
AB  - BACKGROUND: During gait training, physical therapists continuously supervise
      stroke survivors and provide physical support to their pelvis when they judge
      that the patient is unable to keep his balance. This paper is the first in
      providing quantitative data about the corrective forces that therapists use
      during gait training. It is assumed that changes in the acceleration of a
      patient's COM are a good predictor for therapeutic balance assistance during the
      training sessions Therefore, this paper provides a method that predicts the
      timing of therapeutic balance assistance, based on acceleration data of the
      sacrum. METHODS: Eight sub-acute stroke survivors and seven therapists were
      included in this study. Patients were asked to perform straight line walking as
      well as slalom walking in a conventional training setting. Acceleration of the
      sacrum was captured by an Inertial Magnetic Measurement Unit. Balance-assisting
      corrective forces applied by the therapist were collected from two force sensors
      positioned on both sides of the patient's hips. Measures to characterize the
      therapeutic balance assistance were the amount of force, duration, impulse and
      the anatomical plane in which the assistance took place. Based on the
      acceleration data of the sacrum, an algorithm was developed to predict
      therapeutic balance assistance. To validate the developed algorithm, the
      predicted events of balance assistance by the algorithm were compared with the
      actual provided therapeutic assistance. RESULTS: The algorithm was able to
      predict the actual therapeutic assistance with a Positive Predictive Value of 87%
      and a True Positive Rate of 81%. Assistance mainly took place over the medio
      lateral axis and corrective forces of about 2% of the patient's body weight (15.9
      N (11), median (IQR)) were provided by therapists in this plane. Median duration
      of balance assistance was 1.1 s (0.6) (median (IQR)) and median impulse was 9.4Ns
      (8.2) (median (IQR)). Although therapists were specifically instructed to aim for
      the force sensors on the iliac crest, a different contact location was reported
      in 22% of the corrections. CONCLUSIONS: This paper presents insights into the
      behavior of therapists regarding their manual physical assistance during gait
      training. A quantitative dataset was presented, representing therapeutic balance
      assisting force characteristics. Furthermore, an algorithm was developed that
      predicts events at which therapeutic balance assistance was provided. Prediction
      scores remain high when different therapists and patients were analyzed with the
      same algorithm settings. Both the quantitative dataset and the developed
      algorithm can serve as technical input in the development of (robot-controlled)
      balance supportive devices.

PMID- 29197401
TI  - Neglected zoonotic agents in cattle abortion: tackling the difficult to grow
      bacteria.
AB  - BACKGROUND: Coxiella burnetii, Chlamydia abortus and Leptospira spp. are
      difficult to grow bacteria that play a role in bovine abortion, but their
      diagnosis is hampered by their obligate intracellular lifestyle (C. burnetii, C.
      abortus) or their lability (Leptospira spp.). Their importance is based on the
      contagious spread in food-producing animals, but also as zoonotic agents. In
      Switzerland, first-line routine bacteriological diagnostics in cattle abortions
      is regulated by national law and includes only basic screening by staining for C.
      burnetii due to the high costs associated with extended spectrum analysis. The
      aim of this study was to assess the true occurrence of these zoonotic pathogens
      in 249 cases of bovine abortion in Switzerland by serology (ELISA for anti-C.
      burnetii and C. abortus antibodies and microscopic agglutination test for anti
      Leptospira spp. antibodies), molecular methods (real-time PCR and sequencing of
      PCR products of Chlamydiales-positive cases), Stamp's modification of the Ziehl
      Neelsen (mod-ZN) stain and, upon availability of material, by histology and
      immunohistochemistry (IHC). RESULTS: After seroanalysis the prevalence was 15.9%
      for C. burnetii, 38.5% for C. abortus and 21.4% for Leptospira spp. By real-time
      PCR 12.1% and 16.9% of the cases were positive for C. burnetii and Chlamydiales,
      respectively, but only 2.4% were positive for C. burnetii or Chlamydiales by mod
      ZN stain. Sequencing of PCR products of Chlamydiales-positive cases revealed C.
      abortus in 10% of cases and the presence of a mix of Chlamydiales-related
      bacteria in 5.2% of cases. Pathogenic Leptospira spp. were detected in 5.6% of
      cases. Inflammatory lesions were present histologically in all available samples
      which were real-time PCR-positive for Chlamydiales and Leptospira spp. One of 12
      real-time PCR-positive cases for C. burnetii was devoid of histological lesions.
      None of the pathogens could be detected by IHC. CONCLUSION: Molecular detection
      by real-time PCR complemented by histopathological analysis is recommended to
      improve definitive diagnosis of bovine abortion cases and determine a more
      accurate prevalence of these zoonotic pathogens.

PMID- 29197404
TI  - Integrated mental health care and vocational rehabilitation to improve return to
      work rates for people on sick leave because of exhaustion disorder, adjustment
      disorder, and distress (the Danish IBBIS trial): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Common mental disorders are important contributors to the global
      burden of disease and cause negative effects on both the individual and society.
      Stress-related disorders influence the individual's workability and cause early
      retirement pensions in Denmark. There is no clear evidence that mental health
      care alone will provide sufficient support for vocational recovery for this
      group. Integrated vocational and health care services have shown good effects on
      return to work in other similar welfare contexts. The purpose of the Danish IBBIS
      (Integreret Behandlings- og BeskaeftigelsesIndsats til Sygemeldte) study is to
      examine the efficacy of (1) a stepped mental health care intervention with
      individual stress coaching and/or group-based MBSR and (2) an integrated stepped
      mental health care with individual stress coaching and/or group-based MBSR and
      vocational rehabilitation intervention for people on sick leave because of
      exhaustion disorder, adjustment disorder or distress in Denmark. METHOD/DESIGN:
      This three-armed, parallel-group, randomized superiority trial is set up to
      investigate the effectiveness of a stepped mental health care intervention and an
      integrated mental health care and vocational rehabilitation intervention for
      people on sick leave because of exhaustion disorder, adjustment disorder or
      distress in Denmark. The trial has an investigator-initiated multicenter design.
      Six hundred and three patients will be recruited from Danish vocational
      rehabilitation centers in four municipalities and randomly assigned into three
      groups: (1) IBBIS mental health care integrated with IBBIS vocational
      rehabilitation, (2) IBBIS mental health care and standard vocational
      rehabilitation, and (3) standard mental health care and standard vocational
      rehabilitation. The primary outcome is register-based return to work at 12
      months. The secondary outcome measures are self-assessed level of depression
      (BDI), anxiety (BAI), distress symptoms (4DSQ), work- and social functioning
      (WSAS), and register-based recurrent sickness absence. DISCUSSION: This study
      will contribute with knowledge on the consequence of the current organizational
      separation of health care interventions and vocational rehabilitation regarding
      the individual's process of returning to work after sick leave because of
      exhaustion disorder, adjustment disorder or distress. If the effect on return to
      work, symptom level, and recurrent sick leave is different in the intervention
      groups, this study can contribute with new knowledge on shared care models and
      the potential for preventing deterioration in stress symptoms, prolonged sick
      leave, and recurrent sick leave. TRIAL REGISTRATION: ClinicalTrials.gov,
      registration number: NCT02885519 . Retrospectively registered on 15 August 2016).
      Participants have been included in the IBBIS trial for distress, adjustment
      disorder and exhaustion disorder since April 2016.

PMID- 29197405
TI  - Exploring the diversity of Diplostomum (Digenea: Diplostomidae) in fishes from
      the River Danube using mitochondrial DNA barcodes.
AB  - BACKGROUND: Metacercariae of Diplostomum are important fish pathogens, but
      reliable data on their diversity in natural fish populations are virtually
      lacking. This study was conducted to explore the species diversity and host
      parasite association patterns of Diplostomum spp. in a large riverine system in
      Europe, using molecular and morphological data. METHODS: Twenty-eight species of
      fish of nine families were sampled in the River Danube at Nyergesujfalu in
      Hungary in 2012 and Sturovo in Slovakia in 2015. Isolates of Diplostomum spp.
      were characterised morphologically and molecularly. Partial sequences of the
      'barcode' region of the cytochrome c oxidase subunit 1 (cox1) and complete
      sequences of the nicotinamide adenine dinucleotide dehydrogenase subunit 3 (nad3)
      mitochondrial genes were amplified for 76 and 30 isolates, respectively. The
      partial cox1 sequences were used for molecular identification of the isolates and
      an assessment of haplotype diversity and possible host-associated structuring of
      the most prevalent parasite species. New primers were designed for amplification
      of the mitochondrial nad3 gene. RESULTS: Only lens-infecting Diplostomum spp.
      were recovered in 16 fish species of five families. Barcoding of representative
      isolates provided molecular identification for three species/species-level
      genetic lineages, D. spathaceum, D. pseudospathaceum and 'D. mergi Lineage 2',
      and three single isolates potentially representing distinct species. Molecular
      data helped to elucidate partially the life-cycle of 'D. mergi Lineage 2'. Many
      of the haplotypes of D. spathaceum (16 in total), D. pseudospathaceum (15 in
      total) and 'D. mergi Lineage 2' (7 in total) were shared by a number of fish
      hosts and there was no indication of genetic structuring associated with the
      second intermediate host. The most frequent Diplostomum spp. exhibited a low host
      specificity, predominantly infecting a wide range of cyprinid fishes, but also
      species of distant fish families such as the Acipenseridae, Lotidae, Percidae and
      Siluridae. The nad3 gene exhibited distinctly higher levels of interspecific
      divergence in comparison with the cox1 gene. CONCLUSIONS: This first exploration
      of the species diversity and host ranges of Diplostomum spp., in natural fish
      populations in the River Danube, provided novel molecular, morphological and host
      use data which will advance further ecological studies on the distribution and
      host ranges of these important fish parasites in Europe. Our results also
      indicate that the nad3 gene is a good candidate marker for multi-gene approaches
      to systematic estimates within the genus.

PMID- 29197406
TI  - Non-HDL cholesterol and LDL cholesterol in the dyslipidemic classification in
      patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) always underestimates the
      true cholesterol burden in patients with nonalcoholic fatty liver disease
      (NAFLD). We aimed to compare LDL-C and non-high-density lipoprotein cholesterol
      (non-HDL-C) in the identification of high-risk dyslipidemic phenotypes in those
      with NAFLD. METHODS: We conducted a cross-sectional analysis using a cohort of
      9560 apparently healthy Chinese adults who underwent comprehensive health
      checkups including abdominal ultrasonography. RESULTS: Among 3709 patients with
      NAFLD, the prevalence of abnormal LDL using LDL-C was 68.5%, whereas the
      prevalence was relatively lower when using non-HDL-C (55.9%). The concordance
      between non-HDL-C- and LDL-C-based diagnoses of abnormal LDL was similar in the
      hypertriglyceridemic (? = 0.56; 95% CI 0.52-0.60) and normotriglyceridemic
      subgroups (? = 0.47; 95% CI 0.44-0.51). Non-HDL-C detected fewer patients with
      abnormal LDL than LDL-C in normotriglyceridemic patients. However, non-HDL-C
      detected more patients with abnormal LDL than LDL-C in hypertriglyceridemic
      patients: 114 of the 1662 patients considered as abnormal LDL according to LDL-C
      fell into the normonon-HDL-C phenotype, whereas 204 of the 1662 patients
      considered as abnormal LDL according to non-HDL-C fell into the normoLDL-C
      phenotype. CONCLUSION: Among patients with NAFLD, LDL-C is superior to non-HDL-C
      in the detection of high-risk phenotypes in normotriglyceridemic patients,
      whereas non-HDL-C seems to be superior in hypertriglyceridemic patients.

PMID- 29197407
TI  - Low tidal volume mechanical ventilation against no ventilation during
      cardiopulmonary bypass heart surgery (MECANO): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Postoperative pulmonary complications are a leading cause of
      morbidity and mortality after cardiac surgery. There are no recommendations on
      mechanical ventilation associated with cardiopulmonary bypass (CPB) during
      surgery and anesthesiologists perform either no ventilation (noV) at all during
      CPB or maintain low tidal volume (LTV) ventilation. Indirect evidence points
      towards better pulmonary outcomes when LTV is performed but no large-scale
      prospective trial has yet been published in cardiac surgery. DESIGN: The MECANO
      trial is a single-center, double-blind, randomized, controlled trial comparing
      two mechanical ventilation strategies, noV and LTV, during cardiac surgery with
      CPB. In total, 1500 patients are expected to be included, without any
      restrictions. They will be randomized between noV and LTV on a 1:1 ratio. The noV
      group will receive no ventilation during CPB. The LTV group will receive 5
      breaths/minute with a tidal volume of 3 mL/kg and positive end-expiratory
      pressure of 5 cmH2O. The primary endpoint will be a composite of all-cause
      mortality, early respiratory failure defined as a ratio of partial pressure of
      oxygen/fraction of inspired oxygen <200 mmHg at 1 hour after arrival in the ICU,
      heavy oxygenation support (defined as a patient requiring either non-invasive
      ventilation, mechanical ventilation or high-flow oxygen) at 2 days after arrival
      in the ICU or ventilator-acquired pneumonia defined by the Center of Disease
      Control. Lung recruitment maneuvers will be performed in the noV and LTV groups
      at the end of surgery and at arrival in ICU with an insufflation at +30 cmH20 for
      5 seconds. Secondary endpoints are those composing the primary endpoint with the
      addition of pneumothorax, CPB duration, quantity of postoperative bleeding, red
      blood cell transfusions, revision surgery requirements, length of stay in the ICU
      and in the hospital and total hospitalization costs. Patients will be followed
      until hospital discharge. DISCUSSION: The MECANO trial is the first of its kind
      to compare in a double-blind design, a no-ventilation to a low-tidal volume
      strategy for mechanical ventilation during cardiac surgery with CPB, with a
      primary composite outcome including death, respiratory failure and postoperative
      pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03098524 . Registered on 27
      February 2017.

PMID- 29197408
TI  - The sleep and circadian modulation of neural reward pathways: a protocol for a
      pair of systematic reviews.
AB  - BACKGROUND: Animal research suggests that neural reward activation may be
      systematically modulated by sleep and circadian function. Whether humans also
      exhibit sleep and circadian modulation of neural reward pathways is unclear. This
      area is in need of further research, as it has implications for the involvement
      of sleep and circadian function in reward-related disorders. The aim of this
      paper is to describe the protocol for a pair of systematic literature reviews to
      synthesise existing literature related to (1) sleep and (2) circadian modulation
      of neural reward pathways in healthy human populations. METHODS: A systematic
      review of relevant online databases (Scopus, PubMed, Web of Science, ProQuest,
      PsycINFO and EBSCOhost) will be conducted. Reference lists, relevant reviews and
      supplementary data will be searched for additional articles. Articles will be
      included if (a) they contain a sleep- or circadian-related predictor variable
      with a neural reward outcome variable, (b) use a functional magnetic resonance
      imaging protocol and (c) use human samples. Articles will be excluded if study
      participants had disorders known to affect the reward system. The articles will
      be screened by two independent authors. Two authors will complete the data
      extraction form, with two authors independently completing the quality assessment
      tool for the selected articles, with a consensus reached with a third author if
      needed. Narrative synthesis methods will be used to analyse the data. DISCUSSION:
      The findings from this pair of systematic literature reviews will assist in the
      identification of the pathways involved in the sleep and circadian function
      modulation of neural reward in healthy individuals, with implications for
      disorders characterised by dysregulation in sleep, circadian rhythms and reward
      function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017064994.

PMID- 29197409
TI  - Matching disease and phenotype ontologies in the ontology alignment evaluation
      initiative.
AB  - BACKGROUND: The disease and phenotype track was designed to evaluate the relative
      performance of ontology matching systems that generate mappings between source
      ontologies. Disease and phenotype ontologies are important for applications such
      as data mining, data integration and knowledge management to support
      translational science in drug discovery and understanding the genetics of
      disease. RESULTS: Eleven systems (out of 21 OAEI participating systems) were able
      to cope with at least one of the tasks in the Disease and Phenotype track. AML,
      FCA-Map, LogMap(Bio) and PhenoMF systems produced the top results for ontology
      matching in comparison to consensus alignments. The results against manually
      curated mappings proved to be more difficult most likely because these mapping
      sets comprised mostly subsumption relationships rather than equivalence. Manual
      assessment of unique equivalence mappings showed that AML, LogMap(Bio) and
      PhenoMF systems have the highest precision results. CONCLUSIONS: Four systems
      gave the highest performance for matching disease and phenotype ontologies. These
      systems coped well with the detection of equivalence matches, but struggled to
      detect semantic similarity. This deserves more attention in the future
      development of ontology matching systems. The findings of this evaluation show
      that such systems could help to automate equivalence matching in the workflow of
      curators, who maintain ontology mapping services in numerous domains such as
      disease and phenotype.

PMID- 29197411
TI  - Systematic reviews of health economic evaluations: a protocol for a systematic
      review of characteristics and methods applied.
AB  - BACKGROUND: The number of systematic reviews of economic evaluations is steadily
      increasing. This is probably related to the continuing pressure on health budgets
      worldwide which makes an efficient resource allocation increasingly crucial. In
      particular in recent years, the introduction of several high-cost interventions
      presents enormous challenges regarding universal accessibility and sustainability
      of health care systems. An increasing number of health authorities, inter alia,
      feel the need for analyzing economic evidence. Economic evidence might
      effectively be generated by means of systematic reviews. Nevertheless, no
      standard methods seem to exist for their preparation so far. The objective of
      this study was to analyze the methods applied for systematic reviews of health
      economic evaluations (SR-HE) with a focus on the identification of common
      challenges. METHODS/DESIGN: The planned study is a systematic review of the
      characteristics and methods actually applied in SR-HE. We will combine validated
      search filters developed for the retrieval of economic evaluations and systematic
      reviews to identify relevant studies in MEDLINE (via Ovid, 2015-present). To be
      eligible for inclusion, studies have to conduct a systematic review of full
      economic evaluations. Articles focusing exclusively on methodological aspects and
      secondary publications of health technology assessment (HTA) reports will be
      excluded. Two reviewers will independently assess titles and abstracts and then
      full-texts of studies for eligibility. Methodological features will be extracted
      in a standardized, beforehand piloted data extraction form. Data will be
      summarized with descriptive statistical measures and systematically analyzed
      focusing on differences/similarities and methodological weaknesses. DISCUSSION:
      The systematic review will provide a detailed overview of characteristics of SR
      HE and the applied methods. Differences and methodological shortcomings will be
      detected and their implications will be discussed. The findings of our study can
      improve the recommendations on the preparation of SR-HE. This can increase the
      acceptance and usefulness of systematic reviews in health economics for
      researchers and medical decision makers. SYSTEMATIC REVIEW REGISTRATION: The
      review will not be registered with PROSPERO as it does not meet the eligibility
      criterion of dealing with clinical outcomes.

PMID- 29197410
TI  - Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via
      regulation of beta-catenin stabilization in cancer stem cells.
AB  - BACKGROUND: Pharmacology-based target identification has become a novel strategy
      leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a
      dietary polyphenol compound, exhibits potent anticancer activities; however, the
      underlying mechanisms remain unclear. The current study sought to determine the
      role and regulation of ACTN4 expression in human breast cancer metastasis and EA
      based therapy. METHODS: The anti-metastasis ability of EA was validated by MMTV
      PyMT mice and in vitro cell models. Drug affinity responsive target stability
      (DARTS) was utilized to identify ACTN4 as the direct target of EA. The metastatic
      regulated function of ACTN4 were assessed by cancer stem cells (CSCs)-related
      assays, including mammosphere formation, tumorigenic ability, reattachment
      differentiation, and signaling pathway analysis. The mechanisms of ACTN4 on beta
      catenin stabilization were investigated by western blotting, co
      immunoprecipitation and ubiquitination assays. The clinical significance of ACTN4
      was based on human tissue microarray (TMA) analysis and The Cancer Genome Atlas
      (TCGA) database exploration. RESULTS: EA inhibited breast cancer growth and
      metastasis via directly targeting ACTN4 in vitro and in vivo, and was accompanied
      by a limited CSC population. ACTN4 knockdown resulted in the blockage of
      malignant cell proliferation, colony formation, and ameliorated metastasis
      potency. ACTN4-positive CSCs exhibited a higher ESA+ proportion, increased
      mammosphere-formation ability, and enhanced in vivo tumorigenesis ability.
      Mechanism exploration revealed that interruption of ACTN4/beta-catenin
      interaction will result in the activation of beta-catenin proteasome degradation.
      Increased ACTN4 expression was directly associated with the advanced cancer
      stage, an increased incidence of metastasis, and poor overall survival period.
      CONCLUSIONS: Taken together, our results suggest that ACTN4 plays an important
      role in breast CSCs-related metastasis and is a novel therapeutic target of EA
      treatment.

PMID- 29197412
TI  - Does motivation matter in upper-limb rehabilitation after stroke? ArmeoSenso
      Reward: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Fifty percent of all stroke survivors remain with functional
      impairments of their upper limb. While there is a need to improve the
      effectiveness of rehabilitative training, so far no new training approach has
      proven to be clearly superior to conventional therapy. As training with rewarding
      feedback has been shown to improve motor learning in humans, it is hypothesized
      that rehabilitative arm training could be enhanced by rewarding feedback. In this
      paper, we propose a trial protocol investigating rewards in the form of
      performance feedback and monetary gains as ways to improve effectiveness of
      rehabilitative training. METHODS: This multicentric, assessor-blinded, randomized
      controlled trial uses the ArmeoSenso virtual reality rehabilitation system to
      train 74 first-ever stroke patients (< 100 days post stroke) to lift their
      impaired upper limb against gravity and to improve the workspace of the paretic
      arm. Three sensors are attached to forearm, upper arm, and trunk to track arm
      movements in three-dimensional space while controlling for trunk compensation.
      Whole-arm movements serve as input for a therapy game. The reward group (n = 37)
      will train with performance feedback and contingent monetary reward. The control
      group (n = 37) uses the same system but without monetary reward and with reduced
      performance feedback. Primary outcome is the change in the hand workspace in the
      transversal plane. Standard clinical assessments are used as secondary outcome
      measures. DISCUSSION: This randomized controlled trial will be the first to
      directly evaluate the effect of rewarding feedback, including monetary rewards,
      on the recovery process of the upper limb following stroke. This could pave the
      way for novel types of interventions with significantly improved treatment
      benefits, e.g., for conditions that impair reward processing (stroke, Parkinson's
      disease). TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02257125 . Registered on
      30 September 2014.

PMID- 29197413
TI  - Timing of oral anticoagulant therapy in acute ischemic stroke with atrial
      fibrillation: study protocol for a registry-based randomised controlled trial.
AB  - BACKGROUND: Oral anticoagulation therapy is recommended for the prevention of
      recurrent ischemic stroke in patients with atrial fibrillation (AF). Current
      guidelines do not provide evidence-based recommendations on optimal time-point to
      start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K
      antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin
      because of faster and more predictable onset of action and potentially a lower
      risk of intracerebral haemorrhage also in the acute phase after an ischemic
      stroke. The TIMING study aims to establish the efficacy and safety of early vs
      delayed initiation of NOACs in patients with acute ischemic stroke and AF.
      METHODS/DESIGN: The TIMING study is a national, investigator-led, registry-based,
      multicentre, open-label, randomised controlled study. The Swedish Stroke Register
      is used for enrolment, randomisation and follow-up of 3000 patients, who are
      randomised (1:1) within 72 h from ischemic stroke onset to either early (<= 4
      days) or delayed (>= 5-10 days) start of NOAC therapy. The primary outcome is the
      composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or
      all-cause mortality within 90 days after randomisation. Secondary outcomes
      include: individual components of the primary outcome at 90 and 365 days; major
      haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days;
      and health economics. In an optional biomarker sub-study, blood samples will be
      collected after randomisation from approximately half of the patients for central
      analysis of cardiovascular biomarkers after study completion. The study is funded
      by the Swedish Medical Research Council. Enrolment of patients started in April
      2017. CONCLUSION: The TIMING study addresses the ongoing clinical dilemma of when
      to start NOAC after an acute ischemic stroke in patients with AF. By the
      inclusion of a randomisation module within the Swedish Stroke Register, the
      advantages of a prospective randomised study design are combined with the
      strengths of a national clinical quality register in allowing simplified
      enrolment and follow-up of study patients. In addition, the register adds the
      possibility of directly assessing the external validity of the study findings.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT02961348 . Registered on 8 November
      2016.

PMID- 29197414
TI  - Integrated mental health care and vocational rehabilitation to improve return to
      work rates for people on sick leave because of depression and anxiety (the Danish
      IBBIS trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Depression and anxiety are among the largest contributors to the
      global burden of disease and have negative effects on both the individual and
      society. Depression and anxiety are very likely to influence the individual's
      work ability, and up to 40% of the people on sick leave in Denmark have
      depression and/or anxiety. There is no clear evidence that treatment alone will
      provide sufficient support for vocational recovery in this group. Integrated
      vocational and health care services have shown good effects on return to work in
      other, similar welfare contexts. The purpose of the IBBIS (Integrated Mental
      Health Care and Vocational Rehabilitation to Individuals on Sick Leave Due to
      Anxiety and Depression) interventions is to improve and hasten the process of
      return to employment for people in Denmark on sick leave because of depression
      and anxiety. METHODS/DESIGN: This three-arm, parallel-group, randomized
      superiority trial has been set up to investigate the effectiveness of the IBBIS
      mental health care intervention and the integrated IBBIS mental health care and
      IBBIS vocational rehabilitation intervention for people on sick leave because of
      depression and/or anxiety in Denmark. The trial has an investigator-initiated
      multicenter design. A total of 603 patients will be recruited from Danish job
      centers in 4 municipalities and randomly assigned to one of 3 groups: (1) IBBIS
      mental health care integrated with IBBIS vocational rehabilitation, (2) IBBIS
      mental health care and standard vocational rehabilitation, and (3) standard
      mental health care and standard vocational rehabilitation. The primary outcome is
      register-based return to work at 12 months. The secondary outcome measures are
      self-assessed level of depression (Beck Depression Inventory II), anxiety (Beck
      Anxiety Inventory), stress symptoms (Four-Dimensional Symptom Questionnaire),
      work and social functioning (Work and Social Adjustment Scale), and register
      based recurrent sickness absence. DISCUSSION: This study will provide new
      knowledge on vocational recovery, integrated vocational and health care
      interventions, and prevention of recurrent sickness absence among people with
      depression and anxiety. If the effect on return to work is different in the
      intervention groups, this study can contribute to current knowledge on shared
      care models for health care and vocational rehabilitation services. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02872051 . Retrospectively registered on 15
      August 2016.

PMID- 29197416
TI  - Joint awareness in posttraumatic osteoarthritis of the knee: validation of the
      forgotten joint score in long term condition after tibial plateau fracture.
AB  - BACKGROUND: Evaluating patient-reported outcomes (PRO) in early osteoarthritis
      (OA) of the knee is difficult. Established measurement tools are focused on one
      of the two major patient groups in knee surgery: young, highly active patients,
      or older patients with advanced degenerative OA of the knee. Joint awareness in
      everyday life is a crucial criterion in measuring PRO. The purpose of this study
      was to validate a German version of the "Forgotten Joint Score" (FJS) in patients
      after surgical treatment of tibial plateau fractures. METHODS: In this
      prospective cohort study, clinical and radiological outcomes data were collected
      from patients after surgical treatment of tibial plateau fractures following a
      skiing accident. Functional outcome questionnaires were administered including
      the FJS, the Lysholm-Score, the Tegner-Activity Scale (TAS), the EuroQol-5D (EQ 5
      D), and a subjective rating of change. The validation study was carried out
      according to the COSMIN checklist protocol. The KLS was used to measure the
      presence and severity of OA on knee radiographs, and correlation with the FJS was
      measured. RESULTS: Cronbach's alpha was .96 (95%-CI .92, .99) confirming good
      internal consistency. Test-retest reliability of the FJS was high with an ICC(67)
      = .91 (95%-CI .85,.95). Furthermore, no relevant floor or ceiling effects were
      observed. FJS significantly differed in patients with different OA degrees (p =
      .041). Symptomatic patients had significant lower FJS than asymptomatic patients
      (p < .001). CONCLUSIONS: This is the first study validating a disease-specific
      PRO, the FJS, in long-term outcomes after joint fracture. We demonstrated good
      psychometric properties and a significant correlation between the FJS and the
      radiologic degree of OA in patients with a history of tibial plateau fracture.
      TRIAL REGISTRATION: Clinical Trial Registry University of Regensburg Z-2015-0872
      2 . Registered 01. October 2015.

PMID- 29197415
TI  - Variability in adherence to clinical practice guidelines and recommendations in
      COPD outpatients: a multi-level, cross-sectional analysis of the EPOCONSUL study.
AB  - BACKGROUND: Clinical audits have reported considerable variability in COPD
      medical care and frequent inconsistencies with recommendations. The objectives of
      this study were to identify factors associated with a better adherence to
      clinical practice guidelines and to explore determinants of this variability at
      the the hospital level. METHODS: EPOCONSUL is a Spanish nationwide clinical audit
      that evaluates the outpatient management of COPD. Multilevel logistic regression
      with two levels was performed to assess the relationships between individual and
      disease-related factors, as well as hospital characteristics. RESULTS: A total of
      4508 clinical records of COPD patients from 59 Spanish hospitals were evaluated.
      High variability was observed among hospitals in terms of medical care. Some of
      the patient's characteristics (airflow obstruction, degree of dyspnea,
      exacerbation risk, presence of comorbidities), the hospital factors (size and
      respiratory nurses available) and treatment at a specialized COPD outpatient
      clinic were identified as factors associated with a better adherence to
      recommendations, although this only explains a small proportion of the total
      variance. CONCLUSION: To be treated at a specialized COPD outpatient clinic and
      some intrinsic patient characteristics were factors associated with a better
      adherence to guideline recommendations, although these variables were only
      explaining part of the high variability observed among hospitals in terms of COPD
      medical care.

PMID- 29197417
TI  - Simulation modeling for stratified breast cancer screening - a systematic review
      of cost and quality of life assumptions.
AB  - BACKGROUND: The economic evaluation of stratified breast cancer screening gains
      momentum, but produces also very diverse results. Systematic reviews so far
      focused on modeling techniques and epidemiologic assumptions. However, cost and
      utility parameters received only little attention. This systematic review
      assesses simulation models for stratified breast cancer screening based on their
      cost and utility parameters in each phase of breast cancer screening and care.
      METHODS: A literature review was conducted to compare economic evaluations with
      simulation models of personalized breast cancer screening. Study quality was
      assessed using reporting guidelines. Cost and utility inputs were extracted,
      standardized and structured using a care delivery framework. Studies were then
      clustered according to their study aim and parameters were compared within the
      clusters. RESULTS: Eighteen studies were identified within three study clusters.
      Reporting quality was very diverse in all three clusters. Only two studies in
      cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in
      the quality appraisal. In addition to the quality appraisal, this review assessed
      if the simulation models were consistent in integrating all relevant phases of
      care, if utility parameters were consistent and methodological sound and if cost
      were compatible and consistent in the actual parameters used for screening,
      diagnostic work up and treatment. Of 18 studies, only three studies did not show
      signs of potential bias. CONCLUSION: This systematic review shows that a closer
      look into the cost and utility parameter can help to identify potential bias.
      Future simulation models should focus on integrating all relevant phases of care,
      using methodologically sound utility parameters and avoiding inconsistent cost
      parameters.

PMID- 29197418
TI  - Tagging to endogenous genes of Plasmodium falciparum using CRISPR/Cas9.
AB  - BACKGROUND: Plasmodium falciparum is the deadliest malaria parasite. Currently,
      there are seldom commercial antibodies against P. falciparum proteins, which
      greatly limits the study on Plasmodium. CRISPR/Cas9 is an efficient genome
      editing method, which has been employed in various organisms. However, the use of
      this technique in P. falciparum is still limited to gene knockout, site-specific
      mutation and generation of green fluorescent protein (GFP) reporter line with
      disruption of inserted sites. RESULTS: We have adapted the CRISPR/Cas9 system to
      add commercial tag sequences to endogenous genes of P. falciparum. To add HA or
      HA-TY1 tags to ck2beta1, ck2alpha and stk, pL6cs-hDHFR-ck2beta1/ck2alpha/stk was
      constructed, which contained sequences of tags, specific homologous arms, and
      sgRNA. The P. falciparum 3D7 strain was subsequently transfected with pUF1-BSD
      Cas9 and pL6cs-hDHFR-ck2beta1/ck2alpha/stk plasmids via electroporation. After
      that, BSD and WR99210 drugs were added to the culture to screen parasites
      containing both plasmids. Twenty days after electroporation, live parasites
      appeared and were collected to check the tagging by PCR, DNA sequencing, Western
      blotting and immuno-fluorescence assays. The results showed that the tags were
      successfully integrated into the C-terminus of these three proteins. CONCLUSIONS:
      We have improved the method to integrate tags to Plasmodium falciparum genes
      using the CRISPR/Cas9 method, which lays the foundation for further study of
      Plasmodium falciparum at the molecular level.

PMID- 29197419
TI  - Underexplored diversity of gill monogeneans in cichlids from Lake Tanganyika:
      eight new species of Cichlidogyrus Paperna, 1960 (Monogenea: Dactylogyridae) from
      the northern basin of the lake, with remarks on the vagina and the heel of the
      male copulatory organ.
AB  - BACKGROUND: Lake Tanganyika harbours the most diverse cichlid assemblage of the
      Great African Lakes. Considering its cichlid flocks consist of approximately 250
      endemic species, we can hypothesize a high species-richness in their often quite
      host-specific monogenean ectoparasites belonging to Cichlidogyrus Paperna, 1960.
      Yet, only 24 species were described from Tanganyikan hosts and some host tribes
      have never been investigated for monogeneans. This study presents the first
      parasitological examination of species of the tribes Cyprichromini (Cyprichromis
      microlepidotus (Poll, 1956)), Eretmodini (Eretmodus marksmithi Burgess, 2012 and
      Tanganicodus irsacae Poll, 1950) and Ectodini (Aulonocranus dewindti (Boulenger,
      1899)). Specimens of the ectodine Ophthalmotilapia nasuta (Poll & Matthes, 1962)
      from which four Cichlidogyrus spp. have been previously described from more
      southern localities were also studied. Further, we discuss the haptor
      configuration in Tanganyikan Cichlidogyrus spp. and highlight the morphological
      diversity of the vagina, and that of the heel, a sclerotized part of the male
      copulatory organ, absent in some species of Cichlidogyrus. METHODS: Cichlidogyrus
      spp. were isolated from gills and fixed using GAP. Haptoral and genital hard
      parts were measured and drawn by means of a phase contrast microscopic
      examination. RESULTS: We describe eight new species: Cichlidogyrus milangelnari
      n. sp. on C. microlepidotus; C. jeanloujustinei n. sp. on E. marksmithi; C.
      evikae n. sp. on T. irsacae; C. aspiralis n. sp., C. glacicremoratus n. sp. and
      C. rectangulus n. sp. on O. nasuta; and C. pseudoaspiralis n. sp. and C.
      discophonum n. sp. on A. dewindti. Three haptoral morphotypes were recognized
      among the new species. Species of Cichlidogyrus from closely related hosts
      exhibited the same morphotypes. Geographical variation in Cichlidogyrus spp.
      fauna as observed in O. nasuta and three morphotypes were distinguished. Finally,
      we listed 111 Cichlidogyrus species, of which 27 and three Tanganyikan species
      lack sclerotized vagina and heel, respectively, just like 19 and seven species
      outside of the lake. CONCLUSIONS: Haptoral and genital features in the
      Tanganyikan Cichlidogyrus fauna reflect the phylogenetic relationships of their
      cichlid hosts. It seems that several lineages of Cichlidogyrus spp. exist in Lake
      Tanganyika but further studies are necessary to confirm this hypothesis and
      answer questions related to Lake Tanganyika and its cichlids.

PMID- 29197420
TI  - Ovarian mucinous borderline tumor accompanied by LGESS with myxoid change: a case
      report and literature review.
AB  - OBJECTIVES: To report an extremely rare case of ovarian borderline mucinous
      cystic tumor accompanied by low-grade endometrial stromal sarcoma (LGESS) with
      myxoid change. CASE PRESENTATION: A 42-year-old woman complained of lower left
      abdominal fullness. Her serum carcinoembryonic antigen, cancer antigen (CA) 125,
      and CA19-9 levels were normal. Magnetic resonance imaging showed a 10-cm cystic
      mass with a 5-cm nodule in its wall, and a laparoscopy indicated a cystic mass at
      the left adnexa. Histology indicated a cystic lesion consisting of proliferative
      gastrointestinal-type epithelium; the mural nodule had a characteristic of
      striking myxoid change, preservation of arteriolar pattern, and a "tongue-like"
      infiltration. CONCLUSIONS: The diagnosis of ovarian mucinous borderline tumor
      accompanied by LGESS with myxoid change was appropriate.

PMID- 29197421
TI  - Epidemiology of viral hepatitis in the Republic of Congo: review.
AB  - OBJECTIVE: Considered an endemic zone, Republic of Congo has a high
      seroprevalence rate of hepatitis B and C virus. To know the extent of hepatitis
      infection as a public health problem, we reviewed published literature and other
      sources for reports of these viral infections in the country. RESULTS: High
      seroprevalence of HBV and HCV carriage in blood donors were observed in studies
      confirming Congo's place in the hyperendemic area of HBV and HCV infection. These
      prevalence were compared by Chi square test. We compared the prevalence of three
      studies conducted in 1996, 2015 and 2016. The statistical results were very
      significant. HBV genotype E was most prevalent. Very few studies were done on
      pregnant women. Difficulties in the care and management of patients were also
      noted because of the high cost of often unavailable treatments. Difficulties
      arise, however, when an attempt was made to implement the National Hepatitis
      Control Program. Despite studies conducted on hepatitis prevalence, health
      interventions are still needed to care and manage these patients and the need to
      implement the national hepatitis control is more pressing in the Congo.

PMID- 29197422
TI  - The acaricidal speed of kill of orally administered fluralaner against poultry
      red mites (Dermanyssus gallinae) on laying hens and its impact on mite
      reproduction.
AB  - BACKGROUND: Dermanyssus gallinae, the poultry red mite, is a growing threat to
      chickens in poultry farms. This nocturnal hematophagous ectoparasite has a rapid
      rate of proliferation with a negative impact on the birds' health, welfare and
      productivity resulting in severe economic consequences for poultry farmers. A
      study was performed with fluralaner, a novel systemic ectoparasiticide, to
      evaluate its effect on mite vitality and reproduction after oral administration
      to laying hens. METHODS: Sixteen healthy hens were randomly allocated to two
      study groups (n = 8). One group was orally treated with fluralaner by gavage at a
      dose of 0.5 mg/kg bodyweight twice 7 days apart. The negative control group
      received no treatment. Hens in each group were repeatedly infested with
      approximately 200 unfed adult D. gallinae at 1, 5, 8, 12, 15, 19, 22 and 26 days
      after the initial administration. After infestation and feeding for 2.5 h, 25
      engorged mites per hen were collected and incubated in tubes. Mites were assessed
      for vitality (dead/live) at 4, 8, 12, and 24 h after each infestation. Tubes
      containing eggs and/or living mites were incubated another 8 days for assessment
      of mite reproductive capacity. RESULTS: Fluralaner demonstrated a fast speed of
      kill in mites within 4 h post-infestation for 12 days after treatment initiation.
      An efficacy (mite mortality) of 98.7-100% was achieved. At 15 days after
      treatment initiation, 100% efficacy was achieved within 24 h post-infestation,
      and no mite oviposition occurred during this period. Nineteen days after
      treatment initiation, the mites' ability to generate nymphs was reduced by 90.8%,
      which decreased to < 24.1% at later infestations. CONCLUSIONS: Fluralaner
      administered orally to hens twice, 7 days apart, provides efficacy against
      experimental poultry red mite infestation for at least 2 weeks. The demonstrated
      rapid speed of kill results in substantial depletion of the mites' oviposition
      and suggests that fluralaner can be an effective tool in the control of D.
      gallinae, one of the most urgent problems in poultry farms.

PMID- 29197423
TI  - Amnestic MCI patients' experiences after disclosure of their amyloid PET result
      in a research context.
AB  - BACKGROUND: Biomarkers such as amyloid imaging are increasingly used for
      diagnosis in the early stages of Alzheimer's disease. Very few studies have
      examined this from the perspective of the patient. To date, there is only limited
      evidence about how patients experience and value disclosure in an early disease
      stage. METHODS: Semistructured interviews were carried out with 38 patients with
      amnestic mild cognitive impairment as part of an investigator-driven diagnostic
      trial (EudraCT, 2013-004671-12; registered on 20 June 2014) in which participants
      could opt to know the binary outcome (positive/negative) result of their amyloid
      positron emission tomography (PET) scan. Verbatim transcripts of the interviews
      were evaluated using qualitative content analysis and NVivo 11 software. RESULTS:
      Eight of 38 patients received a positive amyloid PET scan result, and the
      remaining 30 patients received a negative amyloid PET scan result. After
      disclosure of the result to the patients, we interviewed each patient twice: 2
      weeks after disclosure and 6 months after disclosure. Patients had difficulties
      in repeating the exact words used during disclosure of their amyloid PET scan
      result by the neurologist; yet, they could recall the core message of the result
      in their own words. Some patients were confused by the terminology of an amyloid
      positive/negative test result. At 6 months, two of eight patients with a positive
      amyloid PET scan result experienced emotional difficulties (sadness, feeling
      worried). Three of 30 patients with a negative amyloid PET scan result started to
      doubt whether they had received the correct result. Patients reported that they
      experienced advantages after the disclosure, such as information about their
      health status, the possibility of making practical arrangements, medication,
      enjoying life more, and a positive impact on relationships. They also reported
      disadvantages following disclosure, such as having emotional difficulties,
      feeling worried about when their symptoms might worsen, the risk of a more
      patronizing attitude by relatives, and the possibility of a wrong diagnosis.
      CONCLUSIONS: This exploratory study shows that the majority of patients can
      accurately recall the information received during disclosure. The experienced
      advantages and disadvantages reported by our patients depended on the outcome of
      the result (positive or negative) and the interval of the conducted interview (2
      weeks or 6 months after amyloid PET disclosure). Discrepancies were found between
      patients' expectations according to the interview prior to amyloid PET disclosure
      (Vanderschaeghe et al. [Neuroethics. 2017;10:281-97]) and their actual
      experiences after their amyloid PET disclosure.

PMID- 29197424
TI  - MetaLab: an automated pipeline for metaproteomic data analysis.
AB  - BACKGROUND: Research involving microbial ecosystems has drawn increasing
      attention in recent years. Studying microbe-microbe, host-microbe, and
      environment-microbe interactions are essential for the understanding of microbial
      ecosystems. Currently, metaproteomics provide qualitative and quantitative
      information of proteins, providing insights into the functional changes of
      microbial communities. However, computational analysis of large-scale data
      generated in metaproteomic studies remains a challenge. Conventional proteomic
      software have difficulties dealing with the extreme complexity and species
      diversity present in microbiome samples leading to lower rates of peptide and
      protein identification. To address this issue, we previously developed the
      MetaPro-IQ approach for highly efficient microbial protein/peptide identification
      and quantification. RESULT: Here, we developed an integrated software platform,
      named MetaLab, providing a complete and automated, user-friendly pipeline for
      fast microbial protein identification, quantification, as well as taxonomic
      profiling, directly from mass spectrometry raw data. Spectral clustering adopted
      in the pre-processing step dramatically improved the speed of peptide
      identification from database searches. Quantitative information of identified
      peptides was used for estimating the relative abundance of taxa at all
      phylogenetic ranks. Taxonomy result files exported by MetaLab are fully
      compatible with widely used metagenomics tools. Herein, the potential of MetaLab
      is evaluated by reanalyzing a metaproteomic dataset from mouse gut microbiome
      samples. CONCLUSION: MetaLab is a fully automatic software platform enabling an
      integrated data-processing pipeline for metaproteomics. The function of sample
      specific database generation can be very advantageous for searching peptides
      against huge protein databases. It provides a seamless connection between peptide
      determination and taxonomic profiling; therefore, the peptide abundance is
      readily used for measuring the microbial variations. MetaLab is designed as a
      versatile, efficient, and easy-to-use tool which can greatly simplify the
      procedure of metaproteomic data analysis for researchers in microbiome studies.

PMID- 29197425
TI  - Physical abrasion method using submerged spike balls to remove algal biofilm from
      photobioreactors.
AB  - OBJECTIVE: A major factor in practical application of photobioreactors (PBR) is
      the adhesion of algal cells onto their inner walls. Optimized algal growth
      requires an adequate sunlight for the photosynthesis and cell growth. Limitation
      in light exposure adversely affects the algal biomass yield. The removal of the
      biofilm from PBR is a challenging and expansive task. This study was designed to
      develop an inexpensive technique to prevent adhesion of algal biofilm on tubular
      PBR to ensure high efficiency of light utilization. Rubber balls with surface
      projections were introduced into the reactor, to remove the adherent biofilm by
      physical abrasion technique. RESULTS: The floatation of spike balls created a
      turbulent flow, thereby inhibiting further biofilm formation. The parameters such
      as, specific growth rate and doubling time of the algae before introducing the
      balls were 0.451 day-1 and 1.5 days respectively. Visible biofilm impeding light
      transmission was formed by 15-20 days. The removal of the biofilm commenced
      immediately after the introduction of the spike balls with visibly reduced
      deposits in 3 days. This was also validated by enhance cell count (6.95 * 106
      cells mL-1) in the medium. The employment of spike balls in PBR is an
      environmental friendly and economical method for the removal of biofilm.

PMID- 29197426
TI  - Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian
      schoolchildren five years into a preventative chemotherapy national control
      programme.
AB  - BACKGROUND: Schistosoma mansoni is a parasite of profound medical importance.
      Current control focusses on mass praziquantel (PZQ) treatment of populations in
      endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes
      exert prolonged selection pressures on parasites with the potential for, direct
      and/or indirect, emergence of drug resistance. Molecular methods can help monitor
      genetic changes of schistosome populations over time and in response to drug
      treatment, as well as estimate adult worm burdens through parentage analysis.
      Furthermore, methods such as in vitro drug sensitivity assays help phenotype in
      vivo parasite genotypic drug efficacy. METHODS: We conducted combined in vitro
      PZQ efficacy testing with population genetic analyses of S. mansoni collected
      from children from two schools in 2010, five years after the introduction of a
      National Control Programme. Children at one school had received four annual PZQ
      treatments and the other school had received two mass treatments in total. We
      compared genetic differentiation, indices of genetic diversity, and estimated
      adult worm burden from parasites collected in 2010 with samples collected in 2005
      (before the control programme began) and in 2006 (six months after the first PZQ
      treatment). Using 2010 larval samples, we also compared the genetic similarity of
      those with high and low in vitro sensitivity to PZQ. RESULTS: We demonstrated
      that there were individual parasites with reduced PZQ susceptibility in the 2010
      collections, as evidenced by our in vitro larval behavioural phenotypic assay.
      There was no evidence, however, that miracidia showing phenotypically reduced
      susceptibility clustered together genetically. Molecular analysis also
      demonstrated a significant reduction of adult worm load over time, despite little
      evidence of reduction in parasite infection intensity, as measured by egg output.
      Genetic diversity of infections did not reduce over time, despite changes in the
      genetic composition of the parasite populations. CONCLUSIONS: Genotypic and
      phenotypic monitoring did not indicate a selective sweep, as may be expected if
      PZQ treatment was selecting a small number of related "resistant" parasites, but
      there was evidence of genetic changes at the population level over time. Genetic
      data were used to estimate adult worm burdens, which unlike parasite infection
      intensity, showed reductions over time, suggesting the relaxation of negative
      density-dependent constraints on parasite fecundity with PZQ treatment. We
      thereby demonstrated that density-dependence in schistosome populations may
      complicate evaluation and monitoring of control programmes.

PMID- 29197427
TI  - Mycobacterium tuberculosis Complex Drug Resistance in a High Tuberculosis
      Incidence Area from the WHO Eastern Mediterranean Region.
AB  - PURPOSE: The incidence of tuberculosis (TB) in Golestan province of Iran has been
      ranked 10th among countries of World Health Organization (WHO) Eastern
      Mediterranean Region. The province is residence of ethnically heterogeneous
      groups. However, there are limited data on Mycobacterium tuberculosis drug
      resistance in this province. The main aim of this study was to determine the
      resistance profile of M. tuberculosis complex (MTBC) isolates to first-line anti
      TB drugs. METHODS: The clinical specimens were collected from 11807 cases
      diagnosed during this study. MTBC isolates were tested for susceptibility to
      first-line anti-TB drugs. RESULTS: A total of 176 new cases were diagnosed as
      culture positive for MTBC. There was one case that had multidrug-resistant (MDR)
      isolate and 18 (10.2%) had isolates that were resistant to at least one drug (any
      drug resistant). Resistance to streptomycin and isoniazid was noted in 15 (8.5%)
      and 5 isolates (2.8%), respectively. Also, a statistically significant
      association was observed between age groups and any drug resistance pattern (p =
      0.022): 1-24 years vs. 25-45 years (p = 0.033), 25-45 years vs. >65 years (p =
      0.010), 46-65 years vs. >65 years (p = 0.050). One third of any drug resistant
      isolates were obtained from TB patients of Persian ethnic group. CONCLUSION:
      Despite the high incidence of TB, the rate of MDR-TB in Golestan province was
      similar to those reported by WHO for Iranian new cases from other regions. One
      tenth of the studied isolates showed any drug resistance pattern. This rate of
      any drug resistance implies the possibility of initial resistance of MTBC
      isolates circulating in this region.

PMID- 29197428
TI  - Thiazolidinedione or Rhodanine: A Study on Synthesis and Anticancer Activity
      Comparison of Novel Thiazole Derivatives.
AB  - PURPOSE: A new series of thiazolyl-2,4-thiazolidinedione / rhodanine compounds T1
      T23 was synthesized and tested for their anticancer activities. Hepatocellular
      carcinoma cell lines were chosen due to their strong drug resistance to test the
      new compounds. METHODS: All compounds were synthesized via Knoevenagel
      Condensation reaction and thiazolidinedione ester compounds (T3,T9,T15,T20) were
      hydrolyzed for obtaining the acidic compounds (T6,T12,T17,T23). All compounds
      were firstly screened for their anticancer activity against two hepatocellular
      carcinoma (HCC) cell lines, Huh7 and Plc/Prf/5 (Plc) cell lines by sulforhodamine
      B assay. Further IC50 values were calculated for three candidates (T4, T15, T21)
      in five different HCC (Huh7, Plc, Snu449, HepG2, Hep3B) and one breast cancer
      (Mcf7) cell line. RESULTS: Compounds T4, T15, T21 had very strong anticancer
      effects even though their 10 uM concentration in Huh7 cell line. According to
      IC50 values, T21 was the most effective compound with IC50 values in a range from
      2 to 16 uM in 6 cancer cell lines. In terms of cytotoxicity T21 mostly affected
      Huh7 and interestingly it was less effective against Plc. CONCLUSIONS:
      Considering these results it can be suggested that compounds T4, T15 and T21 may
      lead to the development of more potent anticancer drugs in the future. This
      article is open to POST-PUBLICATION REVIEW. Registered readers (see "For
      Readers") may comment by clicking on ABSTRACT on the issue's contents page.

PMID- 29197429
TI  - The Economic Contribution of Industry-Sponsored Pharmaceutical Clinical Trials.
AB  - PURPOSE: In pharmaceutical clinical trials, industrial sponsors pay for study
      drugs and related healthcare services. We conducted a study to determine
      industry's economic contribution of these trials to the Alberta healthcare
      system.  Methods: We used data from two trial centers for cancer and non-cancer
      trials at the University of Alberta. For each trial (cancer, non-cancer), we
      calculated the cost of drugs provided by the sponsors using the market price, the
      cost of clinical services, and the cost of administrative services that they
      paid. We extrapolated these results to all trials in Alberta based on information
      obtained from the registration website ClinicalTrials.gov.  Results: Our sample
      consisted of 40 non-cancer and 39 cancer drug trials which were initiated in
      2012. The monetary value of the industry sponsors' contribution was $799,055 per
      non-cancer and $630,243 per cancer drug trial. Drugs (in-trial and post-trial)
      accounted for 84% of the total contribution of the non-cancer drug trials whereas
      it represented 93% of all trial-related contributions in the cancer category. The
      total province-wide contribution of industry-sponsored drug trials which were
      initiated in 2012 was estimated to be $101 million, including open-label drugs in
      the non-cancer category.  Conclusions: Industry-sponsored pharmaceutical trials
      represent a major economic contributor to clinical research within the province.

PMID- 29197430
TI  - Corrigendum to "Methodology for reliable and reproducible cryopreservation of
      human cervical tissue" [Cryobiology 77 (August) (2017) 14-18].

PMID- 29197431
TI  - Measuring Adherence to Evidence-Based Clinical Practice Guidelines.
AB  - OBJECTIVES: Dental Health Services Victoria publishes evidence-based clinical
      practice guidelines (CPGs) to assist public oral health practitioners to provide
      high-quality dental care. How well these CPGs are implemented into practice is
      unknown. The aim of this study was to assess adherence to selected CPGs. METHODS:
      An electronic auditing tool was developed using clinical indicators derived for
      "stainless steel crown (SSC)," "restorative care for children under general
      anesthetic (GA)," and "direct restorative materials" CPG. Six trained dentists
      audited a random sample of 204 dental records of children aged 3-12 years from 2
      major public dental agencies. RESULTS: In total, 319 material-based treatments
      were audited, comprising 170 resin composite, 81 glass ionomer cement, 64 SSC,
      and 4 amalgam restorations. Adherence to the current guidelines varied from 94%
      of the SSC to none of the amalgam treatments audited. Almost half (47%) of the
      resin composite restorations and 5% of glass ionomer cement restorations were
      nonadherent to the relevant guideline. CONCLUSIONS: Average adherence was up to
      72% of cases. Clinicians need to consider recording the rationale upon which
      their professional judgment is based when they decide not to follow an
      appropriate CPG.

PMID- 29197432
TI  - Predoctoral and Postdoctoral Education on Cone-Beam Computed Tomography.
AB  - OBJECTIVES: As the use of cone beam computed tomography (CBCT) in dentistry
      continues to grow, questions related to appropriate radiation safety, training,
      and interpretation arise. Recognizing this need, the American Dental Association
      published an advisory statement for the safe use of CBCT in dentistry and
      recommended that guidelines for appropriate training be established. The purpose
      of this study was to assess radiation safety concerns related to CBCT and
      identify voids in current education on CBCT for the predoctoral dental curriculum
      and continuing dental education. METHODS: A survey was mailed to general
      practitioners, oral surgeons, and periodontists in the Georgia Dental Association
      (n = 415). RESULTS: One hundred twenty-one surveys were received for a response
      rate of 29%. Sixty-eight percent of practitioners reported using CBCT, with 89%
      having used it for over 2 years. Few (12.4%) had experience with CBCT in dental
      school. Interest in continuing dental education on CBCT was reported at 59.8% and
      43.6% for current users and nonusers of CBCT, respectively. Approximately 50%
      reported using precautionary radiation safety measures, and the methods used were
      varied. CONCLUSIONS: Although a higher survey return rate would allow for
      stronger evidence, this project identified some areas of education voids
      including radiation safety and the factors that contribute to patient dose; CBCT
      basics including instruction on the limitations of CBCT; CBCT anatomy and
      pathology with additional time dedicated to the paranasal sinuses; and
      interpretation.

PMID- 29197433
TI  - Outcomes of Dental Implant Therapy in Patients With Down Syndrome: A Systematic
      Review.
AB  - OBJECTIVES: Patients with Down syndrome (DS) require an earlier and more frequent
      tooth replacement than rest of the population. The objective of this systematic
      review is to critically analyze and summarize studies to ascertain the outcomes
      and survival of dental implants placed in jaws of DS patients. METHODS: Using the
      key words "dental implants," "Down syndrome," and "prosthodontics," an electronic
      search was conducted via PubMed/MEDLINE, ISI Web of Science, Google Scholar,
      Embase, and Central Register of Controlled Trials (CENTRAL) databases by 2
      authors, S.N. and Z.K., independently. Retrieved studies were screened against
      the predefined exclusion and inclusion criteria. To estimate the risk of bias,
      quality assessment of included studies was carried using the 'Case Reports (CARE)
      guidelines'. RESULTS: Primary search resulted in 156 studies. Eight studies met
      the inclusion criteria and reporting a total of 81 dental implants placed in 36
      DS patients. The type of implant loading ranged from immediate to a delay of 1
      year after placement of the implant. Implant diameter ranged from 3.3 to 4.5 mm,
      and height ranged from 8.5 to 18 mm. The follow-up ranged from 1 to 6 years. Of
      81 implants placed, 21 implants (26%) were reported as failed. CONCLUSIONS:
      Patients with DS have a higher risk of implant failure. However, the reason for
      the failure is not very well understood. Although case reports and case series
      suggest that implant survival is diminished in DS patients, large-scale
      randomized controlled trials are required to determine the exact mechanism
      associated with risks of implant failure.

PMID- 29197434
TI  - Erbium Laser Technology vs Traditional Drilling for Caries Removal: A Systematic
      Review with Meta-Analysis.
AB  - OBJECTIVE: The study aimed to assess the efficacy of erbium laser technology
      compared with traditional drilling for caries removal. METHODS: A systematic
      search was conducted through Medline via PubMed, Embase, Cochrane databases, CNKI
      till December 2016. Randomised controlled trials, quasi-randomized controlled
      trials, or controlled clinical trials with data comparing the efficacy of erbium
      laser technology versus traditional drilling for caries removal were included.
      RESULTS: Fourteen studies were selected in our meta-analysis. Erbium laser
      technology showed an increased time when removing caries compared with drilling
      (mean difference: 3.48, 95% confidence interval: 1.90-5.06, P < .0001). However,
      erbium laser technology reduced the requirement for local anesthesia (risk ratio:
      0.28, 95% confidence interval: 0.13-0.62, P = .002). Erbium laser technology was
      also not significantly different to traditional drilling with regard to
      restoration loss, pulpal vitality, and postoperative sensitivity. CONCLUSIONS:
      Erbium laser technology showed an increased time for cavity preparation compared
      with traditional drilling. However, erbium laser technology reduced the
      requirement for local anesthesia. There was no significant difference between
      erbium laser technology and traditional drilling regarding restoration loss,
      pulpal vitality, and postoperative sensitivity.

PMID- 29197435
TI  - Gap Analysis of Older Adults With Type 2 Diabetes Receiving Nonsurgical
      Periodontal Therapy.
AB  - OBJECTIVE: Twenty percent of the elderly US population is diagnosed with
      diabetes. The elderly are at a higher risk of developing serious complications
      from diabetes. Regular professional dental care may help control blood glucose
      levels and thereby diabetes complications. Since such potential benefits could
      play a clinically significant role in diabetes management, our aim was to
      identify and review relevant evidence among the older population. MATERIALS AND
      METHODS: Electronic databases were searched for periodontal intervention studies
      using modified search terms from previous systematic reviews. The final search
      date was October 31, 2016. RESULTS: Twenty-five publications (22 studies) were
      included in our final review. They varied in study design, duration, therapeutic
      interventions, and systemic outcomes measured. No study restricted its
      participants to seniors, and therefore, a mean age of 55 years or more was used.
      Fourteen studies showed significant reductions in serum glycated hemoglobin
      levels, but 8 studies showed nonsignificant changes. CONCLUSION: The evidence
      suggests a beneficial effect of receiving periodontal care on serum glycated
      hemoglobin and systemic biomarker levels in older persons with T2DM. Such care
      would be considered a novel, safe, and acceptable adjunct to current medical
      management of T2DM in older individuals. The dearth of studies restricted to the
      elderly represents a gap in knowledge that needs to be addressed in the United
      States.

PMID- 29197436
TI  - A Novel Evidence-Based Periodontal Prognosis Model.
AB  - OBJECTIVE: Patients with periodontal disease and the dental professionals
      responsible for their care want to know which teeth are expected to respond
      favorably to periodontal treatment and which teeth are likely to be lost in the
      short and long term. A number of different periodontal prognosis systems have
      been previously proposed but do not consider important patient-level factors,
      such as smoking and diabetic control, in the calculation of the expected outcome
      and often use subjective measures that introduce potential inaccuracies. The aim
      of this report is to translate the best available evidence on periodontal
      prognosis into a clinical model to facilitate decision-making and improve patient
      outcomes. METHODS: Criteria for an ideal prognostic system were proposed and used
      to assess the previously reported models. With an emphasis on the inclusion of
      patient-level modifiers (PLMs) and the exclusive use of objective parameters, a
      new evidence-based model was developed. RESULTS: This report proposes a new tooth
      level prognosis model that uses 9 evidence-based quantifiable parameters to
      provide a prognosis of secure, doubtful, poor, or irrational to treat. Six tooth
      level risk predictors (bone loss:age, pocket depth, furcation involvement,
      infrabony defects, anatomical factors, and mobility) and 3 PLMs (smoking,
      diabetes, and bleeding on probing) are used to determine the expected course of
      disease with specific reference to the suitability of the tooth for future dental
      treatment. CONCLUSIONS: PLMs must be considered when determining the prognosis of
      a tooth with periodontal disease. The model proposed in this report is based on
      the best available evidence for factors affecting tooth survival and has been
      designed to be as simple and objective as possible to facilitate its adoption in
      clinical practice. It will be retrospectively and prospectively validated to
      determine its ability to accurately predict the course of disease.

PMID- 29197437
TI  - Periodontal Diseases and Systemic Disorders: What Do Our Doctors Know? A General
      Practitioner's Survey Conducted in Southern France.
AB  - OBJECTIVES: With 39,359 entries on PubMed, periodontal medicine has a prominent
      position in periodontal research. Good patient care requires well-advised
      physicians, and whereas the dental community is informed about the relationships
      between periodontal diseases (PDs) and an increasing number of systemic
      pathologies, we wondered whether general practitioners were too. Thus, we aimed
      to evaluate their knowledge of the links between periodontal and systemic
      diseases. METHODS: To this end, we sent an electronic questionnaire to the 2350
      general practitioners registered to the URPS (Union regionale des Professionnels
      de Sante) of Midi-Pyrenees, France. They were asked about their practice, their
      attitude during a medical examination, and their knowledge about PDs. RESULTS:
      The analysis of 222 properly answered questionnaires showed that while most
      general practitioners are aware of the relationships between PDs and diabetes or
      cardiovascular diseases, the majority of them are unaware that obesity and
      respiratory and joint diseases are also concerned. Indeed, 94% of the questioned
      subjects consider their insight of PDs to be insufficient. Nevertheless, more
      than half of the interrogated physicians cared about their patients' oral health
      and dental care. CONCLUSIONS: Education regarding relationships between
      periodontal and systemic diseases must be improved among general practitioners
      who are in the front line to refer high-risk patients to a periodontist.

PMID- 29197438
TI  - Clinical Outcomes of Comparing Soft Tissue Alternatives to Free Gingival Graft: A
      Systematic Review and Meta-Analysis?.
AB  - OBJECTIVES: This systematic review and meta-analysis aimed to compare clinical
      outcomes and width of keratinized tissue (KT) around teeth, following the soft
      tissue alter- natives and free gingival graft (FGG) procedures. The specific
      graft materials that were explored were extracellular matrix membrane, bilayer
      collagen membrane, living cellular construct, and acellular dermal matrix.
      METHODS: Four different databases were queried to identify human controlled
      clinical trials and randomized controlled clinical trials that fulfilled the
      eligibility criteria. Relevant studies were identified by 3 independent
      reviewers, compiling the results of the electronic and handsearches. Studies
      identified through electronic and handsearches were reviewed by title, abstract,
      and full text using Covidence Software. Primary outcome in the present study was
      change in the width of KT. Results of the included studies were pooled to
      estimate the effect size, expressed as weighted mean differences and 95%
      confidence interval. A random-effects model was used to perform the meta
      analyses. RESULTS: Six hundred thirty-eight articles were screened by title, 55
      articles were screened by abstracts, and 34 full-text articles were reviewed.
      Data on quantitative changes in width of KT were provided in 7 studies.
      Quantitative analyses revealed a significant difference in changes in width of KT
      between patients treated with soft tissue alternatives and patients treated with
      FGGs (P < .001). The weighted mean difference of changes in the width of KT was
      21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%),
      indicating patients who were treated with soft tissue alternatives gained 1.39 mm
      less KT width compared with the patients who received free gingival graft.
      CONCLUSIONS: Based on the clinical outcomes, the results of this systematic
      review and meta-analysis showed that soft tissue alternatives result in an
      increased width of KT. Patients in the soft tissue alternatives group obtained
      1.39 mm less KT compared with those in the FGGs group.

PMID- 29197439
TI  - Halitosis Assessment and Changes in Volatile Sulfur Compounds After Chewing Gum:
      A Study Performed on Dentistry Students.
AB  - OBJECTIVE: The objective of this study is to estimate the prevalence of halitosis
      (with subjective and objective methods), evaluate the immediate effect of chewing
      gum on volatile sulfur compounds (VSCs), assess the perception of halitosis by
      dentistry students, and estimate the distribution of positive and negative
      frequencies, when comparing objective and subjective methods for the diagnosis of
      halitosis. METHODS: The study was performed on a sample of dentistry students
      attending the Faculty of Medicine and Health Sciences at the University of
      Barcelona. A questionnaire about halitosis perception was provided and a clinical
      examination, organoleptic test (OT), and gas chromatography were performed to
      determine the presence of halitosis. The subjects were also given chewing gum to
      modify their breath, and gas chromatography was carried out to evaluate possible
      changes in VSCs. RESULTS: The sample comprised 80 individuals. Twenty-seven
      (33.75%) self-perceived halitosis during the period of evaluation; the OT was
      positive in 38 subjects (47.5%); and individuals positive for halitosis on gas
      chromatography were distributed as follows: H2S in 25 (31.25%), CH3SH in 28
      (35%), and (CH3)2S in 70 individuals (87.5%). A statistical difference before and
      after chewing gum (P < .05) was found for each VSC; a difference in frequencies
      was observed between the variable OT and H2S (P < .05) and between the OT and
      (CH3)2S (P < .001). There was no significant difference (P > .05) between the
      positive and negative frequencies retrieved between the variable OT and CH3SH and
      between the OT and the student's halitosis perception. CONCLUSION: Prevalence of
      halitosis in the studied sample is high, considering that it comprised healthy
      individuals. The relationship between the OT and gas chromatography is not
      completely established. Chewing gum could be considered a therapeutic alternative
      to decrease or neutralize the amount of VSCs present in oral breath.

PMID- 29197440
TI  - A Quality Analysis of Systematic Reviews in Dentistry, Part 1: Meta-Analyses of
      Randomized Controlled Trials.
AB  - OBJECTIVES: As the volume of publications in dentistry continues to increase,
      clinicians are becoming increasingly reliant on systematic reviews and meta
      analyses as their primary source of evidence. With an increase in the dependence
      on dental metaanalyses, it is important to ensure that they are being conducted
      with as little bias as possible. The objective of this systematic review is to
      assess the quality of therapeutic meta-analyses of randomized controlled trials
      (RCTs) on dental-related topics and to analyze how quality has changed over time.
      METHODS: All relevant studies were searched for through MEDLINE, Embase,
      PsycINFO, and the Cochrane Library. Title, abstract, and full-text review, as
      well as data extraction and quality assessment, were all conducted in duplicate.
      All reviewers used a pilot-tested extraction form that included the AMSTAR
      checklist to assess quality of systematic reviews. A logit link function ordinal
      regression was conducted to evaluate quality improvement trends over time.
      RESULTS: Of the 3832 studies identified, 208 studies were selected for review. Of
      these, 13% provided an a priori design, 53% screened and extracted data in
      duplicate, 29% included gray literature, 63% assessed the quality of included
      studies, and 39% assessed publication bias. As was indicated by the ordinal
      regression, the quality of meta-analyses, as per the AMSTAR criteria, has
      increased significantly with time (P < .001). CONCLUSIONS: This investigation
      illustrates that although the quality of meta-analyses of RCTs has been
      increasing since the start of the millennium, there remains substantial room for
      improvement within all aspects of systematic review reporting and methodology.
      Therefore, it is critical for clinicians to take caution when reading systematic
      reviews and meta-analyses, ensuring that the principals of critical appraisal are
      applied when interpreting meta-analyses of RCTs.

PMID- 29197441
TI  - No Evidence Suggests that the Clinical Effectiveness of Conventional Occlusal
      Splints is Superior to That of Psychosocial Interventions for Myofascial
      Tempromandibular Disorders Pain.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: A systematic review and meta
      analysis of usual treatment versus psychosocial interventions in the treatment of
      myofascial temporomandibular disorder pain. Fan Roldan-Barraza C, Janko S,
      Villanueva J, Araya I, Lauer HC. J Oral Facial Pain Headache 2014;28(3):205-22.
      SOURCE OF FUNDING: Self-funding TYPE OF STUDY/DESIGN: Systematic review and meta
      analysis.

PMID- 29197442
TI  - Zygomatic Implants Are a Reliable Treatment Option for Patients With Atrophic
      Maxilla.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Survival and Complications of
      Zygomatic Implants: An Updated Systematic Review. Chrcanovic BR, Albrektsson T,
      Wennerberg A. J Oral Maxillofac Surg 2016;74(10):1949-64. SOURCE OF FUNDING: Self
      funding TYPE OF STUDY/DESIGN: Systematic review and meta-analysis.

PMID- 29197443
TI  - High Level of Disagreement Exists Concerning the Prosthetic Maintenance of
      Different Mandibular Implant Overdentures.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Prosthetic maintenance of different
      mandibular implant overdentures: A systematic review. Assaf A, Daas M, Boittin A,
      Eid N, Postaire M. J Prosthet Dent 2017; 118(2):144-52. SOURCE OF FUNDING:
      Information not available TYPE OF STUDY/DESIGN: Systematic review.

PMID- 29197444
TI  - A Leukocyte- and Platelet-Rich Fibrin Showed a Regenerative Potential in
      Intrabony Defects and Furcation Defects but Not in Periodontal Plastic Surgery.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Regenerative potential of leucocyte-
      and platelet-rich fibrin. Part A: intra-bony defects, furcation defects and
      periodontal plastic surgery. A systematic review and meta-analysis. Castro AB,
      Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, Quirynen M. J Clin
      Periodontol 2017; 44(1):67-82. SOURCE OF FUNDING: Self-funded by the authors and
      their institution TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of
      data.

PMID- 29197445
TI  - Patients Are More Satisfied With Implant-Supported Mandibular Overdentures Than
      With Conventional Dentures.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Comparison of implant supported
      mandibular overdentures and conventional dentures on quality of life: a
      systematic review and meta-analysis of randomized controlled studies.
      Sivaramakrishnan G, Sridharan K. Aust Dent J. 2016; 61(4):482-8. SOURCE OF
      FUNDING: The authors received no financial support for this study. TYPE OF
      STUDY/DESIGN: Systematic review.

PMID- 29197446
TI  - Children With Autism Spectrum Disorders can be Successfully Examined Using Dental
      Desensitization.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Predicting successful dental
      examinations for children with autism spectrum disorder in the context of a
      dental desensitization program. Nelson T, Chim A, Sheller BL, McKinney CM, Scott
      JM. J Am Dent Assoc 2017; 148(7): 485-92. SOURCE OF FUNDING: Not available TYPE
      OF STUDY: Cohort study.

PMID- 29197447
TI  - The New Marginal Plaque Index May Allow a More Valid Assessment of Gingival
      Plaque Level Than the Turesky Modification of the Quigley and Hein Index.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Establishment of a new marginal
      plaque index with high sensitivity for changes in oral hygiene. Deinzer R, Jahns
      S, Harnacke D. J Periodontol 2014; 85(12):1730-8. SOURCE OF FUNDING: The study
      was supported by a sponsorship from GABA International, Therwil, Switzerland.
      TYPE OF STUDY/DESIGN: Observational case-control study.

PMID- 29197448
TI  - Motivational Interviewing-Based Approaches in Dental Practice Settings May
      Improve Oral Health Behaviors and Outcomes.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Motivational interviewing in general
      dental practice: A review of the evidence. Kay EJ, Vascott D, Hocking A, Nield H.
      Br Dent J 2016; 221(12):785-91. SOURCE OF FUNDING: National Institute for Health
      Care Excellence (UK) TYPE OF STUDY/DESIGN: Systematic review.

PMID- 29197449
TI  - Poor Oral Health Literacy May Lead to Missed Dental Appointments.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The association between oral health
      literacy and missed dental appointments. Baskaradoss JK. JADA 2016;147(11):867
      74. SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Unmatched
      case-control study that used a convenience nonprobability sampling method.

PMID- 29197450
TI  - Obesity May Be a Risk Factor for Progression of Periodontal Attachment Loss in
      Women.
AB  - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effect of obesity on periodontal
      attachment loss progression: a 5-year population-based prospective study. Gaio
      EJ, Haas AN, Rosing CK, Opermann RV, Albandar JM, Susin C. J Clin Periodontol
      2016;43(7): 557-65. SOURCE OF FUNDING: Foundation for Post-Graduate Education
      (CAPES), Brasilia, Brazil (grant #1614/99-1) Foundation for Research of Rio
      Grande do Sul, Porto Alegre, Brazil (grant #PPSUS-0700481) TYPE OF STUDY/DESIGN:
      Cohort Study.

PMID- 29197451
TI  - Does gender difference mitigate the cardioprotection by pre- and post
      conditioning in the clinical practice?

PMID- 29197452
TI  - Cost-effectiveness of prasugrel versus clopidogrel in acute coronary syndrome
      patients undergoing percutaneous coronary intervention.

PMID- 29197453
TI  - Prasugrel vs clopidogrel in contemporary Western European patients with acute
      coronary syndromes receiving drug-eluting stents: Comparative cost-effectiveness
      analysis from the BASKET-PROVE cohorts - Response to the letter to the Editor.

PMID- 29197454
TI  - Left atrial appendage closure: Six reasons why I wouldn't choose a percutaneous
      closure for my appendage.
AB  - Left atrial appendage has been shown as a primary source of thrombi in patients
      with non-valvular atrial fibrillation (AF). Non vitamin k oral anticoagulants
      (NOAC) have been shown to be safe and effective in the prevention of embolic
      complications. Current guidelines on AF state that percutaneous left atrial
      appendage closure (LAAC) might be considered in patients with contraindication to
      long term oral anticoagulant therapy (OAC). An overview of the main trials on
      NOAC and LAAC is provided.

PMID- 29197455
TI  - Percutaneous left atrial appendage closure versus oral anticoagulant: A bird in
      the hand is worth two in the bush?

PMID- 29197456
TI  - Could excessive atrial ectopic activity be an independent risk factor for
      ischemic stroke?

PMID- 29197457
TI  - "Excessive" atrial ectopy is worse than "frequent" atrial ectopy.

PMID- 29197458
TI  - Should small-to-moderate alcohol consumption be recommended for healthy middle
      aged women?

PMID- 29197459
TI  - Alcohol and atrial fibrillation.

PMID- 29197460
TI  - Atrial fibrillation impacts the outcome in Takotsubo syndrome.

PMID- 29197461
TI  - Ineffective and prolonged apical contraction is associated with chest pain and
      ischaemia in apical hypertrophic cardiomyopathy.
AB  - OBJECTIVES: To investigate the hypothesis that persistence of apical contraction
      into diastole is linked to reduced myocardial perfusion and chest pain.
      BACKGROUND: Apical hypertrophic cardiomyopathy (HCM) is defined by left
      ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic
      contractility resulting in obliteration of the apical cavity is often present.
      Apical HCM can lead to drug-refractory chest pain. METHODS: We retrospectively
      studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical
      septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free
      angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance
      imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi),
      late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional
      contractile persistence (apex, mid and basal LV). RESULTS: In apical HCM, apical
      MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration
      of contractile persistence was associated with lower MPRi (p<0.01) and chest pain
      (p<0.05). In multivariate regression, contractile persistence was independently
      associated with chest pain (p<0.01) and reduced MPRi (p<0.001). CONCLUSION: In
      apical HCM, regional contractile persistence is associated with impaired
      myocardial perfusion and chest pain. As apical myocardium makes limited
      contributions to stroke volume, apical contractility is also largely ineffective.
      Interventions to reduce apical contraction and/or muscle mass are potential
      therapies for improving symptoms without reducing cardiac output.

PMID- 29197462
TI  - Contractile persistence in apical hypertrophic cardiomyopathy: Definitely too
      much of a good thing.

PMID- 29197464
TI  - The thin tracks of periodontal bacteria and the pathogenesis of cardiovascular
      diseases.

PMID- 29197465
TI  - ADDR Editor's Collection 2017.

PMID- 29197463
TI  - Periodontal bacteria DNA findings in human cardiac tissue - Is there a link of
      periodontitis to heart valve disease?
AB  - BACKGROUND: The aim of the study was to detect periodontal pathogens DNA in
      atrial and myocardial tissue, and to investigate periodontal status and their
      connection to cardiac tissue inflammation. METHODS: In 30 patients, biopsy
      samples were taken from the atrium (A) and the ventricle myocardium (M) during
      aortic valve surgery. The dental examination included the dental and periodontal
      status (PS) and a collection of a microbiological sample. The detection of 11
      periodontal pathogens DNA in oral and heart samples was carried out using PCR.
      The heart samples were prepared for detecting the LPS-binding protein (LBP), and
      for inflammation scoring on immunohistochemistry (IHC), comprising macrophages
      (CD68), LPS-binding protein receptor (CD14), and LBP (big42). RESULTS: 28 (93%)
      patients showed moderate to severe periodontitis. The periodontal pathogens in
      the oral samples of all patients revealed a similar distribution (3-93%). To a
      lesser extent and with a different distribution, these bacteria DNA were also
      detected in atrium and myocardium (3-27%). The LBP was detected in higher amount
      in atrium (0.22+/-0.16) versus myocardium (0.13+/-0.13, p=0.001). IHC showed a
      higher inflammation score in atrial than myocardial tissue as well as for CD14,
      CD68 and for LBP. Additional, periodontal findings showed a significant
      correlation to CD14 and CD68. CONCLUSION: The results provide evidence of the
      occurrence of oral bacteria DNA at the cardiac tissue, with a different impact on
      atrial and myocardial tissue inflammation. Influence of periodontal findings was
      identified, but their relevance is not yet distinct. Therefore further clinical
      investigations with long term implication are warranted.

PMID- 29197466
TI  - Kikuchi-Fujimoto Disease with Scalp Involvement.

PMID- 29197467
TI  - Diagnostic Tools to Use When We Suspect an Allergic Reaction to a Tattoo: A
      Proposal Based on Cases at Our Hospital.
AB  - INTRODUCTION: Tattooing has become a popular practice in western countries,
      particularly among younger populations. Tattoos, however, can cause
      complications, such as infections, allergic or foreign-body reactions, and even
      systemic inflammatory responses. PATIENTS AND METHODS: We conducted a
      retrospective study of all patients seen for tattoo-related complications at our
      skin allergy unit between January 2002 and December 2016. RESULTS: We studied 23
      patients. Nine of these experienced early complications, all related to
      infection. The other 14 patients developed late reactions. Ten were diagnosed
      with probable allergic contact dermatitis to ink, but the suspect allergen was
      identified in just 3 cases and confirmed in just 1 of these. There were 2 cases
      of cutaneous sarcoidosis, 1 case of foreign body granuloma, and 1 case of
      neuropathy. CONCLUSIONS: Complications resulting from tattoos are relatively
      common dermatology complaints. Drawing from our experience, we propose a
      diagnostic algorithm designed to guide dermatologists in evaluating different
      reactions to tattoos and prescribing appropriate treatment.

PMID- 29197468
TI  - Characteristics of patients with myelomatous pleural effusion. A systematic
      review.
AB  - BACKGROUND: Myelomatous pleural effusion (MPE) is rare in multiple myeloma, and
      therefore its characteristics are not well defined. METHODS: A systematic review
      (4 online databases) was conducted of articles describing the clinical
      characteristics of patients with MPE, pleural effusion's biochemical
      characteristics and treatment efficacy. We analysed isolated cases and small
      retrospective series. RESULTS: We included 98 articles with a total of 153
      patients with MPE. The median age was 62years, and the ratio of males to females
      was 1.7:1. The most common symptoms were dyspnoea (98.8%), bone pain (100%) and
      chest pain (95.3%), and the most relevant abnormal laboratory test results were
      anaemia (90.1%) and renal failure (53.8%). MPE was predominantly unilateral
      (63.9%) and covered more than two-thirds of the hemithorax (54.5%). The pleural
      fluid (PF) had a haematologic/serohaematologic appearance (87%) and met the
      criteria for lymphocytic (78.6%) exudate (94.7%). The most cost-effective
      diagnostic procedures were pleural cytology (95.9%) and the observation of a
      monoclonal peak in the PF (94.7%). In a significant proportion of patients
      (54.7%), the MPE did not respond to treatment, and the best response was achieved
      when chemotherapy (with/without corticosteroids) was combined with therapeutic
      thoracentesis, chest drainage or pleurodesis. CONCLUSIONS: MPE predominates in
      middle to older age men, is symptomatic and is usually unilateral. PF is an
      exudate with a haemorrhagic appearance, and the most cost-effective diagnostic
      procedure is pleural cytology. Treatment response is unfavourable in more than
      half of patients.

PMID- 29197469
TI  - Editorial.

PMID- 29197470
TI  - Morphologic Findings in Donor (Transplanted) Hearts at Necropsy Early and Late
      After Orthotopic Heart Transplantation.
AB  - Little necropsy information is available on donor hearts in place in recipients
      for varying periods. Necropsy studies were performed in 79 patients who had
      survived from 1 day to 17 years after orthotopic heart transplantation (OHT). At
      OHT, the 79 patients ranged in age from 3 to 70 years (mean 51), and at death,
      from 20 to 76 years (mean 54). The native hearts tended to be larger than the
      donor hearts in the 22 patients surviving <=60 days and the donor hearts tended
      to be larger in the 57 patients surviving >60 days, suggesting that the donor
      hearts increased in weight with time. Cardiac adiposity increased with time.
      Grossly visible myocardial lesions were seen in 24 (30%) of the 79 cases:
      necrosis only in 20; fibrosis only in 2, and both in 2. One or more epicardial
      coronary arteries were narrowed >75% in cross-sectional area in 25 (32%), 1 of
      whom was in the group surviving <=60 days. The right ventricular cavity was
      dilated in 73 cases (92%) and the left ventricular cavity in 39 cases. Evidence
      of graft rejection (lymphocytic infiltrates) was found in 50 patients (63%); in 8
      (36%) of the 22 patients surviving <=60 days, and in 42 (74%) of the 57 surviving
      >60 days. The lymphocytic infiltrates were largest in the subepicardial adipose
      tissue, next in myocardium, and least in endocardium. The quantity of the
      cellular infiltrates varied considerably among the patients. In conclusion, with
      time, the donor hearts tended to increase in weight, in the quantity of adipose
      tissue, in the amounts of coronary narrowing, in the frequency of ventricular
      cavity dilatation (particularly the right ventricle), and in the frequency of
      lymphocytic infiltrates (evidence of rejection).

PMID- 29197471
TI  - Comparison of Utilization Trends, Indications, and Complications of
      Endomyocardial Biopsy in Native Versus Donor Hearts (from the Nationwide
      Inpatient Sample 2002 to 2014).
AB  - Native heart endomyocardial biopsy (NH-EMB) is an infrequently performed
      procedure. The objective of this study is to describe utilization trends,
      indications, and complications associated with NH-EMB in the United States and
      compare them with transplanted heart endomyocardial biopsy (TH-EMB). Using the
      Healthcare Cost and Utilization Project National Inpatient Sample database, we
      identified 71,105 adult patients undergoing EMB in the inpatient setting in
      participating hospitals from 2002 to 2014. A total of 20,770 (29%) were performed
      on NHs (mean age 52.2 +/- 15.3, 61% men). Approximately half of patients were
      white and mean Charlson co-morbidity index was 1.97 +/- 1.6. Common indications
      for NH-EMB included a suspected primary cardiomyopathy (disorder confined to the
      myocardium), heart failure without cardiogenic shock, and acute myocarditis. Less
      common indications included heart failure with cardiogenic shock, unexplained
      heart failure with ventricular tachycardia or high-degree atrioventricular block,
      and cardiac neoplasms. Complications included pericardial effusion (3.8%), third
      degree atrioventricular block (2.7%), vascular complications (1.9%), and deep
      venous thrombosis (3.5%), in others. Predictors of complications included
      presence of a cardiac malignant neoplasm, use of hemodynamic support, heart
      failure with ventricular tachyarrhythmias, and female gender. Compared with NH
      EMB, TH-EMB was associated with lower rates of pericardial effusion, third-degree
      atrioventricular block, ventricular tachyarrhythmias requiring cardioversion, and
      higher rates of deep venous thrombosis, infections, and pneumothorax. NH-EMB
      utilization is low in the United States and constitutes less than 1/3 of all EMBs
      performed.

PMID- 29197472
TI  - Frequency of Inverted Electrocardiographic T Waves (Cerebral T Waves) in Patients
      With Acute Strokes and Their Relation to Left Ventricular Wall Motion
      Abnormalities.
AB  - Transient, symmetric, and deep inverted electrocardiogram (ECG) T waves in the
      setting of stroke, commonly referred to as cerebral T waves, are rare, and the
      underlying mechanism is unclear. Our study aimed to test the hypothesis that
      cerebral T waves are associated with transient cardiac dysfunction. This
      retrospective study included 800 patients admitted with the primary diagnosis of
      hemorrhagic or ischemic stroke. ECGs were examined for cerebral T waves, defined
      as T-wave inversion of >=5 mm depth in >=4 contiguous precordial leads.
      Echocardiograms of those meeting these criteria were examined for the presence of
      left ventricular (LV) wall motion abnormalities. Follow-up evaluation included
      both ECG and echocardiogram. Of the 800 patients, 17 had cerebral T waves on ECG
      (2.1%). All 17 patients had ischemic strokes, of which 11 were in the middle
      cerebral artery distribution (65%), and 2 were cerebellar (12%), whereas the
      remaining 4 involved other locations. Follow-up ECG showed resolution of the T
      wave changes in all 17 patients. Of these patients, 14 (82%) had normal wall
      motion, and 3 had transient wall motion abnormalities (18%). Two of these
      patients had Takotsubo-like cardiomyopathy with apical ballooning, and the third
      had globally reduced LV function. Coronary angiography showed no significant
      disease to explain the LV dysfunction. In summary, in our cohort of patients with
      acute stroke, cerebral T waves were rare and occurred only in ischemic stroke.
      Eighteen percent of patients with cerebral T waves had significant transient wall
      motion abnormalities. Patients with stroke with cerebral T waves, especially in
      those with ischemic strokes, should be assessed for cardiac dysfunction.

PMID- 29197473
TI  - Electrocardiographic Findings in Patients With Acute Coronary Syndrome Presenting
      With Out-of-Hospital Cardiac Arrest.
AB  - We sought to characterize presenting electrocardiographic findings in patients
      with acute coronary syndromes (ACSs) and out-of-hospital cardiac arrest (OHCA).
      In the Global Registry of Acute Coronary Events and Canadian ACS Registry I, we
      examined presenting and 24- to 48-hour follow-up ECGs (electrocardiogram) of ACS
      patients who survived to hospital admission, stratified by presentation with
      OHCA. We assessed the prevalence of ST-segment deviation and bundle branch blocks
      (assessed by an independent ECG core laboratory) and their association with in
      hospital and 6-month mortality among those with OHCA. Of the 12,040 ACS patients,
      215 (1.8%) survived to hospital admission after OHCA. Those with OHCA had higher
      presenting rates of ST-segment elevation, ST-segment depression, T-wave
      inversion, precordial Q-waves, left bundle branch block (LBBB), and right bundle
      branch block (RBBB) than those without. Among patients with OHCA, those with ST
      segment elevation had significantly lower in-hospital mortality (20.9% vs 33.0%,
      p = 0.044) and a trend toward lower 6-month mortality (27% vs 39%, p = 0.060)
      compared with those without ST-segment elevation. Conversely, among OCHA
      patients, LBBB was associated with significantly higher in-hospital and 6-month
      mortality rates (58% vs 22%, p <0.001, and 65% vs 28%, p <0.001, respectively).
      ST-segment depression and RBBB were not associated with either outcome. Sixty
      three percent of bundle branch blocks (RBBB or LBBB) on the presenting ECG
      resolved by 24 to 48 hours. In conclusion, compared with ACS patients without
      cardiac arrest, those with OHCA had higher rates of ST-segment elevation, LBBB,
      and RBBB on admission. Among OHCA patients, ST-segment elevation was associated
      with lower in-hospital mortality, whereas LBBB was associated with higher in
      hospital and 6-month mortality.

PMID- 29197474
TI  - Venomics reveals novel ion transport peptide-likes (ITPLs) from the parasitoid
      wasp Tetrastichus brontispae.
AB  - Despite substantial advances in uncovering constituents of parasitoid venoms due
      to their potential applications as insecticides and pharmaceuticals, most of
      these studies are primarily restricted to braconid and ichneumonid wasps. Little
      information is available regarding virulent factors from venom of Eulophidae. In
      order to provide insight into the venom components of this family and parasitoid
      venom evolution, a venom protein repertoire (venomics) of the endoparasitoid
      wasp, Tetrastichus brontispae was deciphered using a proteomic approach. A large
      number of diverse venom proteins/peptides were identified, including novel
      proteins and those proteins commonly found in the venoms of other parasitoids
      such as serine protease, esterase, dipeptidyl peptidase IV, acid phosphatase,
      major royal jelly protein, superoxide dismutase, and venom allergen 3/5. Three
      ion transport peptide-likes (ITPLs) were abundantly detected in T. brontispae
      venom. Of these, two of them are reported as a novel form for the first time,
      with the characteristics of lengthened amino acid sequences and additional
      cysteine residues. These venom ITPLs are obviously apart from other general
      members within the crustacean hyperglycemic hormone/ion transport peptide
      (CHH/ITP) family. It implies that they would evolve unique functions essential
      for parasitism success.

PMID- 29197475
TI  - Effect of aging on post-saccadic oscillations.
AB  - Recent research have shown that the eye movement data measured by an eye tracker
      does not necessarily reflect the exact rotations of the eyeball. For example,
      post-saccadic eye movements may be more reflecting the relative movements between
      the pupil and the iris rather than the eyeball oscillations. Since, accurate
      measurement of eye movements is important in many studies, it is crucial to
      identify different factors that influence the dynamics of the eye movements
      measured by an eye tracker. Previous studies have shown that deformation of the
      internal structure of the iris and size of the pupil directly affect the
      amplitude of the post-saccadic oscillations that are measured by video-based eye
      trackers that are pupil-based. In this paper, we look at the effect of aging on
      post-saccadic oscillations. We recorded eye movements from a group of 43 young
      and 22 older participants during an abstract and a more natural viewing task. The
      recording was conducted with a video-based eye tracker using the pupil center and
      corneal reflection. We anticipated that changes in the muscle strength as an
      effect of aging might affect, directly or indirectly, the post-saccadic
      oscillations. Results showed that the size of the post-saccadic oscillations were
      significantly larger for our older group. The results suggests that aging has to
      be considered as an important factor when studying the post-saccadic eye
      movements.

PMID- 29197476
TI  - Decreasing length of stay in bariatric surgery: The power of suggestion.
AB  - OBJECTIVE: Enhanced recovery has been utilized to decrease length of stay and
      cost in bariatric surgery. We have recently focused efforts on pre-operative
      education with regards to discharge on the first post-operative day. The aim of
      this study was to determine the effectiveness of pre-operative education on
      discharge timing and readmission rates. METHODS: A retrospective review was
      conducted after revising discharge expectation education. Patients undergoing
      first time bariatric operations were included. Early group education focused on
      average patient stay of 2 postoperative days. Revised education informed patients
      they could go home on the first post-operative day. RESULTS: A total of 125
      patients met inclusion criteria. Implementation of preoperative education was
      associated with a decrease in mean LOS and greater percentage of patients
      discharged on post-operative day one. There was no difference in readmission and
      complication rates. CONCLUSION: Effective pre-operative education can decrease
      length of stay in first time laparoscopic bariatric surgery.

PMID- 29197477
TI  - Neoadjuvant systemic therapy in invasive lobular breast cancer: Is it indicated?
AB  - BACKGROUND: This study investigated patients with invasive lobular breast
      carcinoma (ILC) to determine the benefit of neoadjuvant systemic therapy (NAST).
      METHODS: Patients with ILC treated from 2006 to 2015 were identified. Tumor
      characteristics and treatment data were analyzed. RESULTS: Of the 560 patients
      with ILC, 77 patients received NAST. Patients who received NAST presented with
      larger clinical T stages compared to patients who received surgery first (p <
      0.001). Pathological complete response (pCR) to NAST was seen in 17% of patients.
      Only 14% of patients with clinically positive lymph nodes downstaged to N0. These
      patients were more likely to have HER2 positive tumors (p < 0.029) and larger
      tumor size at diagnosis (p < 0.015). Mastectomy was performed in 84% of patients
      and lumpectomy in 16%. CONCLUSIONS: Only a minority of patients with ILC achieve
      pCR. The majority of patients still undergo mastectomy; therefore the benefit of
      NAST in ILC appears limited.

PMID- 29197479
TI  - Magnetic Resonance Diffusion-Weighted Image of Sister Mary Joseph's Nodule.

PMID- 29197480
TI  - Imagerie par resonance magnetique de diffusion d'un nodule de soeur Marie-Joseph.

PMID- 29197481
TI  - Relevance of Umbilical Growth to Gynaecologists.

PMID- 29197478
TI  - Cardiomyocyte ionic currents in intact young and aged murine Pgc-1beta-/- atrial
      preparations.
AB  - INTRODUCTION: Recent studies reported that energetically deficient murine Pgc
      1beta-/- hearts replicate age-dependent atrial arrhythmic phenotypes associated
      with their corresponding clinical conditions, implicating action potential (AP)
      conduction slowing consequent upon reduced AP upstroke rates. MATERIALS AND
      METHODS: We tested a hypothesis implicating Na+ current alterations as a
      mechanism underlying these electrophysiological phenotypes. We applied loose
      patch-clamp techniques to intact young and aged, WT and Pgc-1beta-/-, atrial
      cardiomyocyte preparations preserving their in vivo extracellular and
      intracellular conditions. RESULTS AND DISCUSSION: Depolarising steps activated
      typical voltage-dependent activating and inactivating inward (Na+) currents whose
      amplitude increased or decreased with the amplitudes of the activating, or
      preceding inactivating, steps. Maximum values of peak Na+ current were
      independently influenced by genotype but not age or interacting effects of
      genotype and age on two-way ANOVA. Neither genotype, nor age, whether
      independently or interactively, influenced voltages at half-maximal current, or
      steepness factors, for current activation and inactivation, or time constants for
      recovery from inactivation following repolarisation. In contrast, delayed outward
      (K+) currents showed similar activation and rectification properties through all
      experimental groups. These findings directly demonstrate and implicate reduced
      Na+ in contrast to unchanged K+ current, as a mechanism for slowed conduction
      causing atrial arrhythmogenicity in Pgc-1beta-/- hearts.

PMID- 29197482
TI  - Pertinence d'une excroissance a l'ombilic en gynecologie.

PMID- 29197483
TI  - Excerpts from the World Medical Literature.

PMID- 29197484
TI  - Extraits de la litterature medicale mondiale.

PMID- 29197485
TI  - Cervical Cancer Screening in Low-Resource Settings.

PMID- 29197486
TI  - The More, the Better? Combining Interventions to Prevent Preterm Birth in Women
      at Risk: a Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To systematically examine the evidence around the combination of
      interventions to prevent preterm birth. METHODS: Without language restrictions,
      we searched clinicaltrials.gov and five electronic databases (Medline, EMBASE,
      CINAHL, Cochrane CENTRAL, and Web of Science) up to July 7, 2016. We included
      randomized and non-randomized studies where asymptomatic women at risk of preterm
      birth received any combination of progesterone, cerclage, or pessary compared
      with either one or no intervention. Primary outcomes were preterm birth <34 and
      <37 weeks and neonatal death. Two independent reviewers extracted data using a
      piloted form and assessed risk and direction of bias. We pooled data with
      unlikely or unclear bias using random-effects meta-analyses. Comparisons with
      likely bias (e.g., confounding by indication) were not pooled. RESULTS: We
      screened 1335 results and assessed 154 full texts, including seven studies. In
      singletons, we found no differences in preterm birth <34 weeks when comparing
      pessary & progesterone with pessary alone (RR 1.30, 95% CI 0.70-2.42) or
      progesterone alone (RR 1.16, 95% CI 0.79-1.72). Similarly, we found no
      differences in preterm birth <37 weeks when comparing cerclage & progesterone
      with cerclage alone (RR 1.04, 95% CI 0.56-1.93) or with progesterone alone (RR
      0.82, 95% CI 0.57-1.19) nor between pessary & progesterone and pessary alone (RR
      1.04, 95% CI 0.62-1.74). No data were available for neonatal death in singletons.
      CONCLUSIONS: Despite being a common clinical practice, evidence to support the
      combined use of multiple versus single interventions for preventing preterm birth
      is scarce.

PMID- 29197487
TI  - No. 352-Technical Update: The Role of Early Comprehensive Fetal Anatomy
      Ultrasound Examination.
AB  - OBJECTIVE: This guideline presents an evidence-based technical update and
      recommendations for the performance of early comprehensive fetal anatomic
      scanning (ECFAS) at 11 to 16 weeks' gestation. OPTIONS: Patients at high risk for
      fetal anomalies and in whom traditional mid-second trimester transabdominal
      imaging may be challenging or who may benefit from earlier identification of
      fetal anomalies may be suitable for early fetal anatomy scanning. OUTCOMES: This
      practice may result in earlier identification of fetal anomalies and provide
      earlier intervention options in high-risk populations and/or in populations where
      mid-second trimester transabdominal scanning is challenging. TARGET POPULATION:
      This population consists of obstetrical patients in whom mid-second trimester
      ultrasound scanning will be technically challenging and patients who are at
      higher risk for major fetal anomalies. EVIDENCE: Published literature was
      retrieved through searches of PubMed and Medline in 2016 using key words. Results
      were restricted to controlled clinical trials, reviews, and observational studies
      published in English. There were no date restrictions, and searches were updated
      in the guideline to 2016. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and clinical practice
      guidelines and national and international medical specialty societies. No
      relevant studies were found. VALIDATION METHODS: The content and recommendations
      were drafted and agreed on by the principal authors. The Board of the SOGC
      approved the final draft for publication. The quality of evidence was rated using
      the criteria described in the Grading of Recommendations Assessment, Development,
      and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, AND/OR COSTS: It
      is anticipated that there will be an increase in earlier detection of major fetal
      anomalies in the target population with the benefits of earlier interventions for
      those individuals. In areas where the service is not available the patient may
      need to travel to a nearby centre. Early fetal anatomy scanning is considered to
      be safe and is not expected to cause a risk to the pregnancy. GUIDELINE UPDATE:
      Evidence will be reviewed 5 years after publication to decide whether all or part
      of the guideline should be updated. However, if important new evidence is
      published before the 5-year cycle, the review process may be accelerated for a
      more rapid update of some recommendations. SPONSORS: This technical update was
      developed with resources funded by the SOGC. SUMMARY STATEMENTS: RECOMMENDATIONS.

PMID- 29197488
TI  - No 352 - Mise a jour technique : Le role de l'examen echographique precoce et
      exhaustif de l'anatomie foetale.

PMID- 29197489
TI  - No. 279-Female Sexual Health Consensus Clinical Guidelines.
AB  - OBJECTIVE: To establish national guidelines for the assessment of women's sexual
      health concerns and the provision of sexual health care for women. EVIDENCE:
      Published literature was retrieved through searches of PubMed, CINAHL, and the
      Cochrane Library from May to October 2010, using appropriate controlled
      vocabulary (e .g., sexuality, "sexual dysfunction," "physiological," dyspareunia)
      and key words (e .g ., sexual dysfunction, sex therapy, anorgasmia). Results were
      restricted, where possible, to systematic reviews, randomized control
      trials/controlled clinical trials, and observational studies. There were no
      language restrictions. Searches were updated on a regular basis and incorporated
      in the guideline to December 2010. Grey (unpublished) literature was identified
      through searching the websites of health technology assessment and health
      technology assessment-related agencies, clinical practice guideline collections,
      clinical trial registries, and national and international medical specialty
      societies. Each article was screened for relevance and the full text acquired if
      determined to be relevant. The evidence obtained was reviewed and evaluated by
      the members of the Expert Workgroup established by The Society of Obstetricians
      and Gynaecologists of Canada. VALUES: The quality of evidence was evaluated and
      recommendations made using the use of criteria described by the Canadian Task
      Force on Preventive Health Care (Table).

PMID- 29197490
TI  - No 279-Directive clinique de consensus sur la sante sexuelle de la femme.

PMID- 29197492
TI  - N degrees  281-Classification des cesariennes au Canada : Les criteres modifies
      de Robson.

PMID- 29197491
TI  - No. 281-Classification of Caesarean Sections in Canada: The Modified Robson
      Criteria.
AB  - OBJECTIVE: To advocate for the use of a common classification system for
      Caesarean section across Canada. OPTIONS: A variety of clinical parameters for
      classification were considered. OUTCOMES: Consideration of a common system for
      classifying Caesarean section. EVIDENCE: Studies published in English from 1976
      to December 2011 were retrieved through searches of Medline and PubMed, using
      appropriate controlled vocabulary and key words (Caesarean section, vaginal birth
      after Caesarean, classification) . Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies.
      Grey (unpublished) literature was identified through searching the web sites of
      health technology assessment and health technology assessment-related agencies,
      clinical practice guideline collections, clinical trial registries, and the web
      sites of national and international medical specialty societies . VALUES: The
      studies reviewed were classified according to criteria described by the Canadian
      Task Force on Preventive Health Care, and the recommendation for practice ranked
      according to this classification (Table 1). SPONSORS: The Society of
      Obstetricians and Gynaecologists of Canada. RECOMMENDATION: Modified Robson
      criteria should be used to enable comparison of Caesarean section rates and
      indications (III-B).

PMID- 29197493
TI  - No. 282-Rural Maternity Care.
AB  - OBJECTIVE: To provide an overview of current information on issues in maternity
      care relevant to rural populations . EVIDENCE: Medline was searched for articles
      published in English from 1995 to 2012 about rural maternity care . Relevant
      publications and position papers from appropriate organizations were also
      reviewed . OUTCOMES: This information will help obstetrical care providers in
      rural areas to continue providing quality care for women in their communities .
      RECOMMENDATIONS: 

PMID- 29197494
TI  - No 282-Soins de maternite en region rurale.

PMID- 29197495
TI  - Use of alternative alkali chlorides in RT and PCR of polynucleotides containing G
      quadruplex structures.
AB  - Several alkali chlorides were compared for their use in reverse transcription
      (RT) and PCR of different types of nucleic acid templates. On a test region of
      biological DNA incapable of forming G quadruplex (G4) structures, Taq DNA
      polymerase showed similar PCR performance with 50 mM KCl, CsCl, LiCl, and NaCl.
      In contrast, on a synthetic model polydeoxyribonucleotide prone to G4 formation,
      good PCR amplification was obtained with 50 mM CsCl, but little or none with LiCl
      or KCl. Similarly, in RT of a G4-prone model polyribonucleotide, MMLV reverse
      transcriptase produced a good yield with 50 mM CsCl, mediocre yields with LiCl or
      without added alkali chloride, and a poor yield with 50 mM KCl. The full RT-PCR
      assay starting from the G4-prone polyribonucleotide, showed good results with
      CsCl in both stages, poor results with LiCl, and no product formation with KCl.
      The model polynucleotides showed fast G quadruplex formation under PCR or RT
      conditions with 50 mM KCl, but not with CsCl or LiCl. The results argue for the
      use of CsCl instead of KCl for RT and PCR of G4-prone sequences. No advantage was
      observed when using the 7-deaza type nucleotide analog c7dGTP in PCR
      amplification of the G4-prone polydeoxyribonucleotide.

PMID- 29197496
TI  - Exploring the links between early life and young adulthood social experiences and
      men's later life psychobiology as fathers.
AB  - Early life cues of environmental harshness and unpredictability have been
      hypothesized to influence within-species variation in the timing of life history
      transitions and the dynamics of reproductive strategies, such as investments in
      mating and parenting. It is also believed that adolesence is an influential
      developmental period for male reproductive strategies, with those who achieve
      greater social and sexual success during that period maintaining faster life
      history strategies into adulthood. If correct, such early life and post-pubertal
      experiences could also help shape the psychobiological pathways that mediate
      reproductive strategies, including the well documented physiological shifts that
      occur when some men become parents. Drawing on a large sample of Filipino men
      (n=417), we evaluate whether men who experienced cues of harshness or
      unpredictability in childhood or have earlier ages at sexual debut have elevated
      testosterone (T) as fathers. We also test whether males who experienced a
      combination of early life experiences of harshness or unpredictability and had
      earlier ages of sexual debut during adolescence had the most elevated T as
      fathers. We found that fathers who experienced early life harshness and who
      engaged in sex at an earlier age had elevated waking T. Among men transitioning
      to fatherhood across the 4.5-year follow-up period of this study, those who
      experienced unpredictability and who engaged in sex at an earlier age showed
      attenuated declines in waking T between baseline and follow-up. Complementing
      these findings, we found that fathers who first engaged in sex at later ages had
      greater acute declines in T when they played with their toddlers. We suggest that
      these patterns could reflect programming effects of sociosexual experiences
      during the years following the marked biological transitions that accompany
      puberty, which occur along with the better-studied effects of earlier life
      exposures to stressors. Overall, our results support the hypothesis that early
      life circumstances and social and sexual experiences, from early life to young
      adulthood, help calibrate physiological axes as key mechanisms coordinating
      dynamic life history strategies.

PMID- 29197497
TI  - Delta-like homolog1/GATA binding protein 2 axis mediates leptin inhibition of
      PPARgamma2 expression in hepatic stellate cells in vitro.
AB  - AIMS: Peroxisome-proliferator activated receptor gamma (PPARgamma) plays a
      pivotal role in inhibition of hepatic stellate cell (HSC) activation, a key step
      for liver fibrogenesis. Adipocyte-derived hormone leptin has been shown to
      promote liver fibrosis in murine and human. PPARgamma includes two subtypes,
      PPARgamma1 and PPARgamma2. Our previous study indicated that leptin down
      regulated PPARgamma1 expression in HSCs. The aim of this study was to investigate
      the effect of leptin on PPARgamma2 expression and the underlying mechanisms in
      HSCs. MAIN METHODS: Real-time PCR and western blot analyses were used to examine
      gene expression. The promoter activities were detected by luciferase assay. KEY
      FINDINGS: Leptin reduced PPARgamma2 expressions at promoter level, mRNA level,
      and protein level in HSCs, which required beta-catenin, p38 mitogen-activated
      protein kinase, and delta-like homolog1 (DLK1) signaling pathways. Leptin induced
      GATA binding protein 2 (GATA2) expression through DLK1 pathway and GATA2 reduced
      PPARgamma2 expression. Ectopic expression of PPARgamma2 reduced the protein
      levels of alpha-smooth muscle actin and alpha1(I)collagen in HSCs. SIGNIFICANCE:
      Since obese patients, often accompanied by hyperleptinemia, are more prone to
      liver fibrosis, the data from this study might have potential implications for
      clarifying the mechanisms for liver fibrogenesis in obese patients with
      hyperleptinemia.

PMID- 29197498
TI  - Combination effect naringin and pravastatin in lipid profile and glucose in obese
      rats.
AB  - AIMS: The purpose of this study was to compare the effect of naringin 100mg/kg in
      combination with pravastatin 10mg/kg by gavage for 6weeks compared with
      monotherapy over lipid profiles, glucose levels and weight in murine model of
      obesity. MAIN METHODS: The study design was planned with 5 groups of 6 male
      Wistar Albina rats: Group 1: control with balanced food and vehicle (C-); Group
      2: control with Obesity and vehicle (C+); Group 3: Obesity+naringin (N); Group 4:
      Obesity+pravastatin (P); Group 5: Obesity+pravastatin+naringin (NP). Obesity was
      developed with a food model. KEY FINDINGS: The naringin groups showed a decrease
      in weight gain and low glucose values compared to the control group (weight
      NP:311.4 vs C+:348.6; glucose NP: 173.12 vs C+:235.56) (p<0.05); the group with
      naringin+pravastatin combination showed the total cholesterol (TC), LDL and
      triglycerides (TGs) to normal levels (TC NP:51.6 vs C+:83.4; LDL NP:9.32 vs
      C+:32.32; TGs NP:39.4 vs C+:89.4) (p<0.05); but was not statistically significant
      compared with monotherapy. SIGNIFICANCE: The combination of naringin and
      pravastatin did not appear to be better than monotherapy on lipids, but its use
      could generate euglycemic and antiobesogenic effects, in addition to diminishing
      the adverse hepatic effects of pravastatin in rats.

PMID- 29197499
TI  - Leptospira reservoirs among wildlife in Brazil: Beyond rodents.
AB  - Leptospirosis is a disease of great importance in tropical regions. Infection
      occurs mainly through contact with water contaminated with the urine of infected
      animals, especially that of rodents. Despite the diversity and abundance of wild
      fauna in Brazil, little is known about the role of other wild species in the
      epidemiology of leptospirosis. This study aimed to investigate new reservoirs of
      Leptospira among wildlife in Brazil, using serological and molecular diagnoses in
      a large-sized sample. Biological samples were collected from 309 free-ranging
      mammals, belonging to 16 species. The majority of the animals included were
      opossums (Didelphis albiventris) and coatis (Nasua nasua). Blood and urine
      samples were subjected to the microscopic agglutination test (MAT) and real-time
      PCR, respectively. Genetic characterization of genomospecies was performed using
      PCR amplicons. Statistical analysis was applied to test associations between
      positive diagnoses and age, sex, season and type of environment. The prevalence
      of infection found via MAT and PCR was 11% and 5.5%, respectively. If these tests
      are taken to be complementary, the overall prevalence was 16%. The most common
      serogroups were Djasiman and Australis, while L. santarosai was the prevalent
      genomospecies. Significant differences in prevalence between animal species were
      observed. Greater risk of infection was detected among adult opossums than among
      young ones. The influence of each serogroup and genomospecies was tested for the
      same variables, and this revealed higher risk of infection by L. santarosai among
      male opossums than among females. The present study highlights the exposure and
      carrier status of several wild species in Brazil and it indicates that coatis and
      other carnivores are priorities for further investigations.

PMID- 29197500
TI  - Dengue endemic and its impact on the gross national product of BRAZILIAN'S
      economy.
AB  - In history disease has caused social and economic damage. Dengue is an illness
      typically found in the tropics that has affected more and more people. In Brazil,
      according to the Brazilian Institute of Geography and Statistics (IBGE), in 2013
      at least 12.9% of the population (25.8 million) reported already having had
      dengue in their life. So, how wide are the economic impacts that dengue's
      contagion has on the gross national product? Using Leontief's method, it became
      possible to estimate the direct and indirect impact on the workforce and output
      by one country. Workforce absenteeism reduced the national productiveness and
      welfare state where we found maximum inoperability of 0.027% and a minimum of
      0.002%. This paper develops a methodology for estimation of the impact dengue has
      incurred in each sector of an economy; designing a ranking with sectors that have
      been more affected and forecasting the propagation of the endemic throughout a
      region. This research measures the impact of dengue on economy, the result was
      that the total loss of the Brazilian economy in 2013 was around BRL
      1,023,174,876.83; the importance of 0.02% of the Gross Domestic Product.

PMID- 29197501
TI  - Intuitive physics ability in systemizers relies on differential use of the
      internalizing system and long-term spatial representations.
AB  - According to the Empathizing-Systemizing theory (E-S Theory), individual
      differences in how people understand the physical world (systemizing) and the
      social world (empathizing), are two continuums in the general population with
      several implications, from vocational interests to skills in the social and
      physical domains. The underlying mechanisms of intuitive physics performance
      among individuals with strong systemizing and weak empathizing (systemizers) are,
      however, unknown. Our results affirm higher intuitive physics skills in healthy
      adult systemizers (N=36), and further reveal the brain mechanisms that are
      characteristic for those individuals in carrying out such tasks. When the
      participants performed intuitive physics tasks during functional magnetic
      resonance imaging, combined higher systemizing and lower empathizing was
      associated with stronger activations in parts of the default mode network (DMN,
      cuneus and posterior cingulate gyrus), middle occipital gyrus, and
      parahippocampal region. The posterior cingulate gyrus and parahippocampal gyrus
      were specifically associated with systemizing "brain type" even after controlling
      for task performance, while especially in the parietal cortex, the activation
      changes were simply explained by higher task performance. We therefore suggest
      that utilization of DMN-parahippocampal complex, suggested to play a role in
      internalizing and activating long-term spatial memory representations, is the
      factor that distinguishes systemizers from empathizers with the opposite "brain
      type" in intuitive physics tasks.

PMID- 29197502
TI  - Functional brain networks underlying idiosyncratic switching patterns in multi
      stable auditory perception.
AB  - In perceptual multi-stability, perception stochastically switches between
      alternative interpretations of the stimulus allowing examination of perceptual
      experience independent of stimulus parameters. Previous studies found that
      listeners show temporally stable idiosyncratic switching patterns when listening
      to a multi-stable auditory stimulus, such as in the auditory streaming paradigm.
      This inter-individual variability can be described along two dimensions,
      Exploration and Segregation. In the current study, we explored the functional
      brain networks associated with these dimensions and their constituents using
      electroencephalography. Results showed that Segregation and its constituents are
      related to brain networks operating in the theta EEG band, whereas Exploration
      and its constituents are related to networks in the lower and upper alpha and
      beta bands. Thus, the dimensions on which individuals' perception differ from
      each other in the auditory streaming paradigm probably reflect separate
      perceptual processes in the human brain. Further, the results suggest that
      networks mainly located in left auditory areas underlie the perception of
      integration, whereas perceiving the alternative patterns is accompanied by
      stronger interhemispheric connections.

PMID- 29197503
TI  - Serum metabolic profiling of type 2 diabetes mellitus in Chinese adults using an
      untargeted GC/TOFMS.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a huge burden in China. The
      Chinese patients with T2DM have several special clinical characteristics.
      Metabolomics studies predominantly have identified several distinguishing
      metabolites associated with T2DM in Western ancestry population. However, few
      previous metabolomics studies were conducted in Chinese populations. METHODS: We
      performed untargeted serum metabolic profiling between 30 T2DM patients and 30
      healthy controls based on GC/TOFMS. Multivariate data analyses were applied to
      identify the distinguishing metabolites. RESULTS: Excellent separation was
      obtained between the two cases. And overall 54 distinguishing metabolites were
      identified with VIP>1 and P<0.05, which were involved in metabolic pathways of
      amino acid, carbohydrate, lipids, membrane transport and nucleotides. To further
      analyze the correlation between the identified metabolites and T2DM, 17
      metabolites were selected with FC>2.0, including gentisic acid, citraconic acid,
      succinic acid, 2-hydroxybutanoic acid and 3-hydroxy-l-proline, the corresponding
      FC were respectively 5.44, 2.21, 2.10, 2.21 and -2.04. CONCLUSION: Our results
      demonstrated that untargeted GC/TOFMS-based metabolic approach processed well
      performance to identify serum distinguishing metabolites of T2DM in Chinese
      adults, which may be as potential biomarkers in diagnose and treatment of
      diabetes. And the results also provided new insight into understand the
      underlying molecular mechanism.

PMID- 29197505
TI  - A safer, urea-based in situ hybridization method improves detection of gene
      expression in diverse animal species.
AB  - In situ hybridization is a widely employed technique allowing spatial
      visualization of gene expression in fixed specimens. It has greatly advanced our
      understanding of biological processes, including developmental regulation. In
      situ protocols are today routinely followed in numerous laboratories, and
      although details might change, they all include a hybridization step, where
      specific antisense RNA or DNA probes anneal to the target nucleic acid sequence.
      This step is generally carried out at high temperatures and in a denaturing
      solution, called hybridization buffer, commonly containing 50% (v/v) formamide -
      a hazardous chemical. When applied to the soft-bodied hydrozoan medusa Clytia
      hemisphaerica, we found that this traditional hybridization approach was not
      fully satisfactory, causing extensive deterioration of morphology and tissue
      texture which compromised our observation and interpretation of results. We thus
      tested alternative solutions for in situ detection of gene expression and,
      inspired by optimized protocols for Northern and Southern blot analysis, we
      substituted the 50% formamide with an equal volume of 8M urea solution in the
      hybridization buffer. Our new protocol not only yielded better morphologies and
      tissue consistency, but also notably improved the resolution of the signal,
      allowing more precise localization of gene expression and reducing aspecific
      staining associated with problematic areas. Given the improved results and
      reduced manipulation risks, we tested the urea protocol on other metazoans, two
      brachiopod species (Novocrania anomala and Terebratalia transversa) and the
      priapulid worm Priapulus caudatus, obtaining a similar reduction of aspecific
      probe binding. Overall, substitution of formamide by urea during in situ
      hybridization offers a safer alternative, potentially of widespread use in
      research, medical and teaching contexts. We encourage other workers to test this
      approach on their study organisms, and hope that they will also obtain better
      sample preservation, more precise expression patterns and fewer problems due to
      aspecific staining, as we report here for Clytia medusae and Novocrania and
      Terebratalia developing larvae.

PMID- 29197504
TI  - Gata6 restricts Isl1 to the posterior of nascent hindlimb buds through Isl1 cis
      regulatory modules.
AB  - Isl1 is required for two processes during hindlimb development: initiation of the
      processes directing hindlimb development in the lateral plate mesoderm and
      configuring posterior hindlimb field in the nascent hindlimb buds. During these
      processes, Isl1 expression is restricted to the posterior mesenchyme of hindlimb
      buds. How this dynamic change in Isl1 expression is regulated remains unknown. We
      found that two evolutionarily conserved sequences, located 3' to the Isl1 gene,
      regulate LacZ transgene expression in the hindlimb-forming region in mouse
      embryos. Both sequences contain GATA binding motifs, and expression pattern
      analysis identified that Gata6 is expressed in the flank and the anterior portion
      of nascent hindlimb buds. Recent studies have shown that conditional inactivation
      of Gata6 in mice causes hindlimb-specific pre-axial polydactyly, indicating a
      role of Gata6 in anterior-posterior patterning of hindlimbs. We studied whether
      Gata6 restricts Isl1 in the nascent hindlimb bud through the cis-regulatory
      modules. In vitro experiments demonstrate that GATA6 binds to the conserved GATA
      motifs in the cis-regulatory modules. GATA6 repressed expression of a luciferase
      reporter that contains the cis-regulatory modules by synergizing with Zfpm2.
      Analyses of Gata6 mutant embryos showed that ISL1 levels are higher in the
      anterior of nascent hindlimb buds than in wild type. Moreover, we detected a
      greater number of Isl1-transcribing cells in the anterior of nascent hindlimb
      buds in Gata6 mutants. Our results support a model in which Gata6 contributes to
      repression of Isl1 expression in the anterior of nascent hindlimb buds.

PMID- 29197506
TI  - Cadmium exposure exacerbates severe hyperlipidemia and fatty liver changes in
      zebrafish via impairment of high-density lipoproteins functionality.
AB  - Cadmium (Cd) is a heavy metal with several toxicities that have destructive
      effect on most organ systems. However, its toxic effects on human lipoproteins
      are largely remained unknown especially in hyperlipidemic zebrafish model.
      Treatment of human high-density lipoprotein (HDL) with cadmium chloride (CdCl2,
      final 12 and 24MUM) caused spontaneous formation of multimeric apoA-I as well as
      increased production of glycated extent products. Cd-HDL3 accelerated uptake of
      oxidized LDL (oxLDL) into macrophages and induced severe senescence in human
      dermal fibroblast (HDF) cells. Microinjection of Cd-HDL3 into zebrafish embryos
      resulted in acute embryonic toxicity with high mortality. Exposure of zebrafish
      embryos to water containing CdCl2 (final 12 and 24MUM) caused early embryonic
      death along with increased production of oxidized products and impairment of
      skeletal development. Consumption of CdCl2 (12 and 24MUM) by zebrafish for 4weeks
      resulted in severe elevation of plasma total cholesterol (TC) and triglyceride
      (TG) levels as well as cholesteryl ester (CE) transfer activity. Furthermore,
      consumption of CdCl2 resulted in acceleration of fatty liver changes and
      increased production of reactive oxygen species (ROS). In conclusion, CdCl2
      caused structural modification of HDL3 and impaired the beneficial functions of
      HDL3, including anti-oxidation, anti-atherosclerosis, and anti-senescence
      effects. Consumption of CdCl2 also resulted in exacerbated hyperlipidemia and
      fatty liver changes in zebrafish via enhancement of cholesteryl ester transfer
      protein (CETP) activity.

PMID- 29197508
TI  - Global asymptotic stability for the SEIRS models with varying total population
      size.
AB  - In this paper, SEIRS epidemiological model with disease caused death and varying
      total population size is discussed. Based on the geometric approach developed by
      Li and Muldowney, a new criterion to determine the global asymptotic stability
      for nonlinear system is proposed. By applying this new criterion, global
      asymptotic stability of the endemic equilibrium when it is unique is proved. The
      above global result shows that the basic reproduction number is a sharp threshold
      for SEIRS model which removes restrictions of rate of loss of immunity and rate
      of disease caused death in Li and Muldowney's result.

PMID- 29197509
TI  - Michaelis-Menten equation for degradation of insoluble substrate.
AB  - Kinetic studies of homogeneous enzyme reactions where both the substrate and
      enzyme are soluble have been well described by the Michaelis-Menten (MM) equation
      for more than a century. However, many reactions are taking place at the
      interface of a solid substrate and enzyme in solution. Such heterogeneous
      reactions are abundant both in vivo and in industrial application of enzymes but
      it is not clear whether traditional enzyme kinetic theory developed for
      homogeneous catalysis can be applied. Since the molar concentration of surface
      accessible sites (attack-sites) often is unknown for a solid substrate it is
      difficult to assess whether the requirement of the MM equation is met. In this
      paper we study a simple kinetic model, where removal of attack sites expose new
      ones which preserve the total accessible substrate, and denote this approach the
      substrate conserving model. The kinetic equations are solved in closed form, both
      steady states and progress curves, for any admissible values of initial
      conditions and rate constants. The model is shown to merge with the MM equation
      and the reverse MM equation when these are valid. The relation between available
      molar concentration of attack sites and mass load of substrate is analyzed and
      this introduces an extra parameter to the equations. Various experimental setups
      to practically and reliably estimate all parameters are discussed.

PMID- 29197507
TI  - Association between a functional interleukin 6 receptor genetic variant and risk
      of depression and psychosis in a population-based birth cohort.
AB  - OBJECTIVE: Interleukin 6 (IL-6) levels are commonly elevated in patients with
      depression and psychosis and in people who are at risk of developing these
      disorders. A common, functional variant in the IL6R gene (IL6R Asp358Ala;
      rs2228145 A > C) is known to dampen down inflammation by impairing IL6R
      signaling. We have examined the association of Asp358Ala with diagnosis of
      depression and psychosis, serum IL-6, CRP levels, and a number of risk factors
      commonly linked with inflammation, depression or psychosis. We predicted that if
      IL-6 were related to depression/psychosis risk causally, rather than due to
      confounding, Asp358Ala would be associated with risk of these disorders, serum IL
      6, CRP levels, but not with any of the confounders. METHOD: We used data from the
      population-based ALSPAC birth cohort. Serum IL-6 and CRP levels were measured at
      age 9 years. Psychotic disorder, ICD-10 diagnosis of severe depressive episode,
      and total depression score were assessed at age 18 years. IL6R Asp358Ala was
      genotyped using the Illumina HumanHap550 quad genome-wide SNP genotyping
      platform. Risk factors assessed include sex, body mass index, social class,
      ethnicity, maternal education, birth weight, gestational age, maternal post-natal
      depression, childhood psychological and behavioral problems, and total IQ score.
      RESULTS: Asp358Ala was associated with decreased risk of severe depression and/or
      psychosis; adjusted odds ratio for those with CC, compared with AA, genotype was
      0.38 (95% CI, 0.15-0.94). The variant was associated with increased serum IL-6
      levels (P = 5.5 * 10-22) but decreased serum CRP levels (P = 3.5 * 10-5),
      consistent with an anti-inflammatory effect downstream of IL-6. Asp358Ala was not
      associated with total depression score. Asp358Ala was not associated with any of
      the other risk factors commonly linked with inflammation, depression or psychosis
      (all P > 0.20). CONCLUSIONS: The findings provide further evidence that the IL
      6/IL6R pathways are involved in pathogenesis of severe depression and psychosis,
      and may be novel therapeutic targets. Previously reported associations between IL
      6, depression and psychosis are unlikely to be fully explained by confounding.
      Based on a small number of cases, findings from the current study need
      replication in other samples.

PMID- 29197510
TI  - An alternative approach to Michaelis-Menten kinetics that is based on the
      renormalization group.
AB  - We apply to Michaelis-Menten kinetics an alternative approach to the study of
      Singularly Perturbed Differential Equations, that is based on the Renormalization
      Group (SPDERG). To this aim, we first rebuild the perturbation expansion for
      Michaelis-Menten kinetics, beyond the standard Quasi-Steady-State Approximation
      (sQSSA), determining the 2nd order contributions to the inner solutions, that are
      presented here for the first time to our knowledge. Our main result is that the
      SPDERG 2nd order uniform approximations reproduce the numerical solutions of the
      original problem in a better way than the known results of the perturbation
      expansion, even in the critical matching region. Indeed, we obtain analytical
      results nearly indistinguishable from the numerical solutions of the original
      problem in a large part of the whole relevant time window, even in the case in
      which the kinetic constants produce an expansion parameter value as large as
      E=0.5.

PMID- 29197511
TI  - Partner-Mediated Polymorphism of an Intrinsically Disordered Protein.
AB  - Intrinsically disordered proteins (IDPs) recognize their partners through
      molecular recognition elements (MoREs). The MoRE of the C-terminal intrinsically
      disordered domain of the measles virus nucleoprotein (NTAIL) is partly pre
      configured as an alpha-helix in the free form and undergoes alpha-helical folding
      upon binding to the X domain (XD) of the viral phosphoprotein. Beyond XD, NTAIL
      also binds the major inducible heat shock protein 70 (hsp70). So far, no
      structural information is available for the NTAIL/hsp70 complex. Using mutational
      studies combined with a protein complementation assay based on green fluorescent
      protein reconstitution, we have investigated both NTAIL/XD and NTAIL/hsp70
      interactions. Although the same NTAIL region binds the two partners, the binding
      mechanisms are different. Hsp70 binding is much more tolerant of MoRE
      substitutions than XD, and the majority of substitutions lead to an increased
      NTAIL/hsp70 interaction strength. Furthermore, while an increased and a decreased
      alpha-helicity of the MoRE lead to enhanced and reduced interaction strength with
      XD, respectively, the impact on hsp70 binding is negligible, suggesting that the
      MoRE does not adopt an alpha-helical conformation once bound to hsp70. Here, by
      showing that the alpha-helical conformation sampled by the free form of the MoRE
      does not systematically commit it to adopt an alpha-helical conformation in the
      bound form, we provide an example of partner-mediated polymorphism of an IDP and
      of the relative insensitiveness of the bound structure to the pre-recognition
      state. The present results therefore contribute to shed light on the molecular
      mechanisms by which IDPs recognize different partners.

PMID- 29197512
TI  - Understanding interactions between populations: Individual based modelling and
      quantification using pair correlation functions.
AB  - Understanding the underlying mechanisms that produce the huge variety of swarming
      and aggregation patterns in animals and cells is fundamental in ecology,
      developmental biology, and regenerative medicine, to name but a few examples.
      Depending upon the nature of the interactions between individuals (cells or
      animals), a variety of different large-scale spatial patterns can be observed in
      their distribution; examples include cell aggregates, stripes of different
      coloured skin cells, etc. For the case where all individuals are of the same type
      (i.e., all interactions are alike), a considerable literature already exists on
      how the collective organisation depends on the inter-individual interactions.
      Here, we focus on the less studied case where there are two different types of
      individuals present. Whilst a number of continuum models of this scenario exist,
      it can be difficult to compare these models to experimental data, since real
      cells and animals are discrete. In order to overcome this problem, we develop an
      agent-based model to simulate some archetypal mechanisms involving attraction and
      repulsion. However, with this approach (as with experiments), each realisation of
      the model is different, due to stochastic effects. In order to make useful
      comparisons between simulations and experimental data, we need to identify the
      robust features of the spatial distributions of the two species which persist
      over many realisations of the model (for example, the size of aggregates, degree
      of segregation or intermixing of the two species). In some cases, it is possible
      to do this by simple visual inspection. In others, the features of the pattern
      are not so clear to the unaided eye. In this paper, we introduce a pair
      correlation function (PCF), which allows us to analyse multi-species spatial
      distributions quantitatively. We show how the differing strengths of inter
      individual attraction and repulsion between species give rise to different
      spatial patterns, and how the PCF can be used to quantify these differences, even
      when it might be impossible to recognise them visually.

PMID- 29197513
TI  - Exploration of Mycobacterium tuberculosis structural proteome: An in-silico
      approach.
AB  - Pharmacophore approaches are of central contour in drug discovery. However, the
      dependence of ligand-based pharmacophore model on appropriate training set
      molecules and typical use of apo-protein or single protein-ligand complex for the
      construction of structure-based pharmacophore models might skip some vital
      information. Therefore, multiple-complex based approach was employed for the
      construction of pharmacophore models of the Mycobacterium structural proteome.
      Moreover, the strategy of clustering of common pharmacophore hypotheses was made
      to gain an insight about the pharmacophore-similarity across the protein classes
      and share of features among the inhibitors. Rationale behind the present work was
      to present the scenario of virtual screening and guiding principle for designing
      efficient inhibitor by taking into account the available pharmacophoric space.

PMID- 29197514
TI  - Mathematical analysis of the transmission dynamics of the liver fluke,
      Opisthorchis viverrini.
AB  - We develop and analyse two population-based models of the transmission dynamics
      of the worm parasite Opisthorchis viverrini. The life cycle of O. viverrini
      includes humans, cats and dogs as definitive hosts; and snails and fish as
      intermediate hosts. The first model has only one definitive host (humans) while
      the second model has two additional hosts: the reservoir hosts, cats and dogs. We
      define reproduction numbers and endemic equilibrium points for the two models. We
      use prevalence data for the five hosts from two islands in Lao People's
      Democratic Republic to estimate distributions of parameter values. We use these
      distributions to compute the sensitivity index and the partial rank correlation
      coefficient of the basic reproduction number and the endemic equilibrium point to
      the parameters. We calculate distributions of the host-specific type-reproduction
      number to show that humans are necessary to maintain transmission and can sustain
      transmission without additional reservoir hosts. Therefore interventions
      targeting humans could be sufficient to interrupt transmission of O. viverrini.

PMID- 29197515
TI  - Fingolimod anti-inflammatory and neuroprotective effects modulation of RAGE axis
      in multiple sclerosis patients.
AB  - BACKGROUND: We investigated Fingolimod treatment effects on the RAGE (receptor
      for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The
      primary outcome of the study was whether Fingolimod treatment increases serum
      levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered
      putative endogenous inhibitors of RAGE signaling. Additional variables were serum
      levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine.
      METHODS: Serum levels of the study variables were measured by ELISA, and compared
      between baseline (before Fingolimod treatment) and 6 and 12 months post-drug
      treatment in 17 relapsing MS patients. Fingolimod treatment effects on MS disease
      progression were assessed by comparing pre- and post-Fingolimod values of the
      EDSS and rate of clinical relapse, and changes in the T1-and T2-enahncing lesions
      on the MRI scan.methods RESULTS: Twelve months treatment with Fingolimod
      increased serum levels of sRAGE and esRAGE by 32.4% (P = 0.004) and 48.5% (P =
      0.007) respectively. In addition, Fingolimod treatment reduced serum levels of
      HMGB1 by 71.6% (P = 0.02) and pentosidine serum levels by 41.3% (P = 0.12). EDSS
      remained stable (baseline: 3.57 +/- 1.56; post-Fingolimod: 3.54 +/- 1.2, P =
      0.96) and the rate of clinical relapse decreased near significantly (P = 0.094).
      T1-and T2-enhancing lesions remained stable, showing no significant changes pre
      vs. post-Fingolimod treatment. CONCLUSION: Fingolimod mediates modulation of the
      RAGE axis which apparently contributes to the Fingolimod's anti-inflammatory and
      neuroprotective effects. These findings may provide a rationale for the clinical
      efficacy of Fingolimod in pathological states other than MS, where dysregulation
      of the RAGE axis plays a role.

PMID- 29197516
TI  - Protopanaxadiol derivative DDPU improves behavior and cognitive deficit in AD
      mice involving regulation of both ER stress and autophagy.
AB  - Alzheimer's disease (AD) is a progressively neurodegenerative disease with
      typical hallmarks of amyloid beta (Abeta) plaque accumulation, neurofibrillary
      tangle (NFT) formation and neuronal death extension. Aggressive Abeta
      accumulation promotes senile plaque formation and perturbs endoplasmic reticulum
      (ER) function to trigger the unfolded protein response (UPR) leading to neuronal
      apoptosis. The stress-dependent activation of protein kinase RNA-like endoplasmic
      reticulum kinase (PERK) increases the phosphorylation of eukaryotic translation
      initiation factor-2alpha (eIF2alpha) to promote the preferential synthesis of
      beta-site APP cleavage enzyme 1 (BACE1) and Abeta generation in turn.
      Additionally, dysfunction in autophagy has been reported to contribute to several
      neurodegenerative diseases including AD, and impairment in autophagy-mediated
      pathway may constitutively stimulate the generation of Abeta in AD. Here we
      discovered that protopanaxadiol derivative 1-(3,4-dimethoxyphenethyl)-3-(3
      dehydroxyl-20(s)-protopanaxadiol-3beta-yl)-urea (DDPU) effectively improved the
      activity of daily living (ADL) and cognitive deficits in APP/PS1 transgenic mice.
      The crosstalk between Abeta and ER stress has been intensively investigated by
      using DDPU as a probe. DDPU reduced Abeta production mainly by inhibiting the
      PERK/eIF2alpha signaling-mediated BACE1 translation and stimulated Abeta
      clearance by promoting autophagy as a PI3K inhibitor through PI3K/AKT/mTOR
      signaling pathway, while exhibited neuroprotective effect involving attenuation
      of ER stress. DDPU might be the first reported ginsenoside derivative with dual
      effects on both autophagy promotion and ER stress amelioration. Our results have
      highlighted the potential of DDPU in the treatment of AD.

PMID- 29197517
TI  - DPI-289, a novel mixed delta opioid agonist / mu opioid antagonist (DAMA), has L
      DOPA-sparing potential in Parkinson's disease.
AB  - L-DOPA-induced dyskinesia (LID) remains a significant problem in the management
      of Parkinson's disease (PD). In rodent and macaque models of PD, delta opioid
      receptor agonists have anti-parkinsonian actions while mu opioid antagonists can
      reduce the expression of LID. DPI-289 is a novel molecule with a unique
      combination of opioid receptor DAMA actions: delta agonist (Ki: 0.73 nM); mu
      antagonist (Ki: 12 nM). We demonstrated that DPI-289 has oral bioavailability and
      established its pharmacokinetic profile in both rat and primate. We hypothesised
      that these combined DAMA actions would provide an enhancement of L-DOPA effect
      without an associated increase in dyskinesia. In parkinsonian 6-OHDA lesioned
      rats and MPTP-lesioned macaques, DPI-289 provided anti-parkinsonian actions as
      monotherapy and an enhancement of L-DOPA benefit. Thus, acute administration of
      DPI-289 (3 mg/kg, p.o.) to 6-OHDA-lesioned rats produced a significant reduction
      in forelimb asymmetry (by 48%) that was maintained throughout the fifteen-day
      repeat-treatment period. Importantly, and in contrast to L-DOPA administration (6
      mg/kg, i.p.), these benefits were not compromised by the development of abnormal
      involuntary movements. In the macaque, as monotherapy, DPI-289 (10 and 20 mg/kg)
      had significant, though incomplete, anti-parkinsonian actions lasting
      approximately 4 h. These benefits were not associated with dyskinesia. In fact,
      over the 6 h period of observation, DPI-289 (20 mg/kg) decreased parkinsonism by
      19% and increased activity by 67% compared to vehicle treatment. By contrast,
      while high-dose L-DOPA (LDh) alone alleviated parkinsonism (for 3 h) this benefit
      was accompanied by significant dyskinesia that was disabling in nature. LDh
      provided a 50% reduction in parkinsonism over 6 h and 151% increase in activity.
      The combination of DPI-289 (20 mg/kg) and a low-dose of L-DOPA (LDl) provided
      anti-parkinsonian benefits greater than LDl alone without eliciting any
      significant dyskinesia. Treatment with LDl alone provided only transient
      statistically significant anti-parkinsonian benefit. However, the combination of
      LDl and DPI-289 reduced parkinsonism for 6 h (duration of monitoring), with
      parkinsonism being reduced by 35% and activity increased by 90% but with no
      increase in dyskinesia over that observed with LDl alone. Thus, DPI-289 has
      potential to improve the benefits of dopaminergic therapy in Parkinson's disease.

PMID- 29197518
TI  - The effect of association between inefficient arsenic methylation capacity and
      demographic characteristics on the risk of skin lesions.
AB  - This study was conducted in rural Pakistan to assess the dose-response
      relationship between skin lesions and arsenic exposure and their variation by
      demographic characteristics. The study included 398 participants (66 participants
      with skin lesions and 332 without) residing in six previously unstudied villages
      exposed to ground water arsenic in the range of <1 to 3090MUgL-1. The skin
      lesions identification process involved interview and physical examinations of
      participants followed by confirmation by a physician according to UNICEF
      criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic
      acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation
      capacity, methylation efficiency and the dose-response relationship with skin
      lesions. Study participants with skin lesions were found to be exposed to arsenic
      >10MUgL-1 with a daily arsenic intake of 3.23+/-3.75mgday-1 from household ground
      water sources for an exposure duration of 10-20years. The participants with skin
      lesions compared to those without skin lesions showed higher levels of urinary
      iAs (133.40+/-242.48 vs. 44.24+/-86.48MUgg-1Cr), MMA (106.38+/-135.04 vs. 35.43+/
      39.97MUgg-1Cr), MMA% (15.26+/-6.31 vs.12.11+/-4.68) and lower levels of DMA%
      (66.99+/-13.59 vs. 73.39+/-10.44) and secondary methylation index (SMI) (0.81+/
      0.11 vs. 0.86+/-0.07). Study participants carrying a lower methylation capacity
      characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64,
      95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12)
      and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin
      lesions compared to their corresponding references after adjusting for occupation
      categories. The findings confirmed that inefficient arsenic methylation capacity
      was significantly associated with increased skin lesion risks and the effect
      might be modified by labour intensive occupations.

PMID- 29197520
TI  - Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation
      promotion cancer model in the mouse.
AB  - Liver fibrosis results from chronic tissue damage and excessive regeneration with
      accumulation of extracellular matrix proteins; it is a precursor of liver
      cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily
      directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is
      a drug approved for idiopathic pulmonary fibrosis and this study was focused on
      anti-fibrotic and anti-cancer potential of pirfenidone in the liver of male
      B6C3F1/J mice. In a dose-finding study, mice were treated with CCl4 (0.2ml/kg ip,
      2*wk for 4weeks) while on a pirfenidone-containing (0-600mg/kg) diet. Pirfenidone
      at doses of 300 and 600mg/kg had significant anti-fibrotic (collagen) and anti
      inflammatory (serum transaminases and "ballooning" hepatocyte) effects. In a sub
      chronic study (14weeks), mice received CCl4 while on pirfenidone (300mg/kg) diet.
      Pirfenidone significantly reduced collagen deposition, but had little effect of
      inflammation and injury. In an initiation-promotion cancer study with N
      nitrosodiethylamine and CCl4, pirfenidone (300mg/kg) did not affect incidence,
      size, or multiplicity of liver tumors. Overall, we conclude that while
      pirfenidone exhibits strong anti-fibrotic effects in early stage liver fibrosis,
      it is less effective in advanced liver fibrosis and was not protective in an
      initiation-promotion liver cancer.

PMID- 29197519
TI  - Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent organic pollutants
      that adversely affect human health. PCBs bio-accumulate in organisms important
      for human consumption. PCBs accumulation in the body leads to activation of the
      transcription factor NF-kappaB, a major driver of inflammation. Despite dietary
      exposure being one of the main routes of exposure to PCBs, the gut has been
      widely ignored when studying the effects of PCBs. OBJECTIVES: We investigated the
      effects of PCB 153 on the intestine and addressed whether PCB 153 affected
      intestinal permeability or inflammation and the mechanism by which this occurred.
      METHODS: Mice were orally exposed to PCB 153 and gut permeability was assessed.
      Intestinal epithelial cells (IECs) were collected and evaluated for evidence of
      genotoxicity and inflammation. A human IEC line (SW480) was used to examine the
      direct effects of PCB 153 on epithelial function. NF-kB activation was measured
      using a reporter assay, DNA damage was assessed, and cytokine expression was
      ascertained with real-time PCR. RESULTS: Mice orally exposed to PCB 153 had an
      increase in intestinal permeability and inflammatory cytokine expression in their
      IECs; inhibition of NF-kB ameliorated both these effects. This inflammation was
      associated with genotoxic damage and NF-kB activation. Exposure of SW480 cells to
      PCB 153 led to similar effects as seen in vivo. We found that activation of the
      ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation.
      CONCLUSIONS: These results demonstrate that oral exposure to PCB 153 is genotoxic
      to IECs and induces downstream inflammation and barrier dysfunction in the
      intestinal epithelium.

PMID- 29197521
TI  - High phosphate-induced downregulation of PPARgamma contributes to CKD-associated
      vascular calcification.
AB  - Medial arterial calcification associated with hyperphosphatemia is a main cause
      of cardiovascular mortality in patients with chronic kidney disease (CKD), but
      the mechanisms underlying high phosphate-induced vascular calcification remain
      largely unknown. Here, we observed a significant decrease in the expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) in calcified
      arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia.
      In vitro, high phosphate treatment led to a decreased expression of PPARgamma in
      mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic
      differentiation and calcification. Pretreatment with PPARgamma agonist
      rosiglitazone significantly reversed high phosphate-induced VSMCs calcification.
      Further investigation showed that methyl-CpG binding protein 2 (Mecp2)-mediated
      epigenetic repression was involved in high phosphate-induced PPARgamma
      downregulation. Moreover, the expression of Klotho that has the ability to
      inhibit vascular calcification by regulating phosphate uptake decreased with the
      PPARgamma reduction in VSMCs after high phosphate treatment, and rosiglitazone
      failed to inhibit high phosphate-induced calcification in VSMCs with knockdown of
      Klotho or in aortic rings from Klotho-deficient (kl/kl) mice. Finally, an in vivo
      study demonstrated that oral administration of rosiglitazone could increase
      Klotho expression and protect against high phosphate-induced vascular
      calcification in CKD mice. These findings suggest that the inhibition of
      PPARgamma expression may contribute to the pathogenesis of high phosphate-induced
      vascular calcification, which may provide a new therapeutic target for vascular
      calcification in CKD patients.

PMID- 29197522
TI  - Urinary Bladder vs Gastrointestinal Tissue: A Comparative Study of Their
      Biomechanical Properties for Urinary Tract Reconstruction.
AB  - OBJECTIVE: To evaluate the mechanical properties of gastrointestinal (GI) tissue
      segments and to compare them with the urinary bladder for urinary tract
      reconstruction. METHODS: Urinary bladders and GI tissue segments were sourced
      from porcine models (n = 6, 7 months old [5 male; 1 female]). Uniaxial planar
      tension tests were performed on bladder tissue, and Cauchy stress-stretch ratio
      responses were compared with stomach, jejunum, ileum, and colonic GI tissue.
      RESULTS: The biomechanical properties of the bladder differed significantly from
      jejunum, ileum, and colonic GI tissue. Young modulus (kPa-measure of stiffness)
      of the GI tissue segments was on average 3.07-fold (+/-0.21 standard error)
      higher than bladder tissue (P < .01), and the strain at Cauchy stress of 50 kPa
      for bladder tissues was on average 2.27-fold (+/-0.20) higher than GI tissues.
      There were no significant differences between the averaged stretch ratio and
      Young modulus of the horizontal and vertical directions of bladder tissue (315.05
      +/- 49.64 kPa and 283.62 +/- 57.04, respectively, P = .42). However, stomach
      tissues were 1.09- (+/-0.17) and 0.85- (+/-0.03) fold greater than bladder
      tissues for Young modulus and strain at 50 kPa, respectively. CONCLUSION: An
      ideal urinary bladder replacement biomaterial should demonstrate mechanical
      equivalence to native tissue. Our findings demonstrate that GI tissue does not
      meet these mechanical requirements. Knowledge on the biomechanical properties of
      bladder and GI tissue may improve development opportunities for more suitable
      urologic reconstructive biomaterials.

PMID- 29197523
TI  - Occurrence of uterine carriers for Leptospira interrogans on slaughtered cows.
AB  - Reproductive tract is an important site of infection for chronic leptospirosis
      and cooperate in pathogenesis of reproductive failure, leading to economic
      losses. Since serology techniques cannot detect chronic carriers, the molecular
      analysis of clinical samples is an alternative to detect these animals on
      livestock. The aim of the present study was to perform a retrospective study in
      order to detect leptospiral uterine carriers in slaughtered cows. Tissue samples
      were collected from 50 post-pubertal, nonpregnant cows. These samples were fixed
      in 10% buffered formalin, paraffin-embedded and stored. PCR targeting lipL32 gene
      and molecular characterization by secY sequence was performed. Leptospiral DNA
      was identified in 18% (9/50) examined blocks. Two sequences were characterized as
      L. interrogans. These findings suggest that the presence of infectious
      leptospires in uterus is associated with the physiopathogenesis of the
      reproductive failure.

PMID- 29197525
TI  - A novel horA genetic mediated RCA detection of beer spoilage lactobacillus.
AB  - As one of the most popular beverage, beer has strong resistance to bacteria
      except for lactic acid bacteria (LAB), as its strong viability in beer.
      Contaminating LAB results in beer spoilage. HorA gene carried by beer spoilage
      lactobacillus confers hop resistance and is associated with the growth of
      Lactobacillus in beer, thus can be used as a perfectly valid genetic marker for
      the detection of beer spoilage Lactobacillus strains. This study applied genome
      and bioinformatics analyses, together with genetic alignment and comparison
      techniques to build a rolling circle amplification (RCA) detection method
      targeted on horA for beer spoilage Lactobacillus. The horA genetic mediated RCA
      method showed rapid, sensitive and specific on beer spoilage lactobacillus
      detection.

PMID- 29197524
TI  - Mercuric resistant bacteria Aeromonas exhibits neurologic toxic effects on the
      developmental motor reflexes, and brain oxidative stress in mice offspring.
AB  - Mercury and its derivatives even in small concentration may cause a major human
      health problem. Though not reported in detail, there are various aquatic
      bacterial species that produce small quantities of methyl mercury (MM) growing
      under aerobic conditions. Consumption of food derived from sources contaminated
      with such bacteria within therapeutic doses and exposure to different forms of MM
      compounds through such sources may induce substantial toxic effects. In the
      present study, the perinatal oral exposure of pregnant mice to two strains of
      mercury resistant bacteria (MRB), Aeromonas KSU5 MRB and KSU6 MRB resulted in a
      significant reduction in postnatal body weight gain, delays in the opening of the
      eyes and appearance in the body hair fuzz, and deficits in the developing sensory
      motor reflexes in the mice pups during their weaning period on post-natal day
      (PD)7, PD14 and PD21. A significant and MM producing concentration-dependent
      disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin
      (5-HT); non-enzymatic oxidative stress (OS) indices like thiobarbituric acid
      reactive substances (TBARS) and total reduced glutathione (GSH); and enzymatic OS
      indices like glutathione S-transferase (GST), catalase (CAT), and superoxide
      dismutase (SOD) were observed in the forebrain region of the offspring at weaning
      period (PD7, PD14, and PD21), at adolescent age (PD30), and at adult age (PD36).
      Thus, perinatal exposure to MRB can affect developing fetus, raising the concerns
      for it's potential neurotoxic hazards. A reduced exposure to mercury during
      pregnancy is of crucial importance in preventing mercury-induced neurotoxicity in
      the offspring.

PMID- 29197526
TI  - Pathway analysis of differentially expressed genes in Mycobacterium bovis
      challenged bovine macrophages.
AB  - The immune signalling genes during the challenge of bovine macrophages with
      bacterial products derived from tuberculosis causing bacteria in cattle were
      investigated in the present study. An in-vitro cell culture model of bovine
      monocyte-derived macrophages were challenged to Mycobacterium bovis. Macrophages
      from healthy and already infected animals can both be fully activated during M.
      bovis infection. Analysis of mRNA abundance in peripheral blood mononuclear cells
      from M. bovis infected and non-infected cattle were performed as a controls.
      Cells of treatment were challenged after six days for six hours incubation at 37 
      degrees C, with 5% CO2, to total RNA was extracted then cDNA labelling,
      hybridization and scanning for microarray methods have been developed for
      microarray based immune related gene expression analysis. The differential
      expressions twenty genes (IL1, CCL3, CXCR4, TNF, TLR2, IL12, CSF3, CCR5, CCR3,
      MAPT, NFKB1, CCL4, IL6, IL2, IL23A, CCL20, IL8, CXCL8, TRIP10, CXCL2 and IL1B)
      implicated in M. bovis response were examined Agilent Bovine_GXP_8 * 60 K
      microarray platform. Cells of treatment were challenged after six days for six
      hours incubation then pathways analysis of Toll like receptor and Chemokine
      signalling pathway study of responsible genes in bovine tuberculosis. The PBMC
      from M. bovis infected cattle exhibit different transcriptional profiles compared
      with PBMC from healthy control animals in response to M. bovis antigen
      stimulation, providing evidence of a novel genes expression program due to M.
      bovis exposure. It will guide future studies, regarding the complex macrophage
      specific signalling pathways stimulated upon phagocytosis of M. bovis and role of
      signalling pathways in creating the host immune response to cattle tuberculosis.

PMID- 29197527
TI  - Subjective neighborhood assessment and physical inactivity: An examination of
      neighborhood-level variance.
AB  - Research suggests a linkage between perceptions of neighborhood quality and the
      likelihood of engaging in leisure-time physical activity. Often in these studies,
      intra-neighborhood variance is viewed as something to be controlled for
      statistically. However, we hypothesized that intra-neighborhood variance in
      perceptions of neighborhood quality may be contextually relevant. We examined the
      relationship between intra-neighborhood variance of subjective neighborhood
      quality and neighborhood-level reported physical inactivity across 48
      neighborhoods within a medium-sized city, Texas City, Texas using survey data
      from 2706 residents collected between 2004 and 2006. Neighborhoods where the
      aggregated perception of neighborhood quality was poor also had a larger
      proportion of residents reporting being physically inactive. However, higher
      degrees of disagreement among residents within neighborhoods about their
      neighborhood quality was significantly associated with a lower proportion of
      residents reporting being physically inactive (p=0.001). Our results suggest that
      intra-neighborhood variability may be contextually relevant in studies seeking to
      better understand the relationship between neighborhood quality and behaviors
      sensitive to neighborhood environments, like physical activity.

PMID- 29197528
TI  - Social capital and obesity among adults: Longitudinal findings from the Montreal
      neighborhood networks and healthy aging panel.
AB  - Curbing the worldwide increase in obesity requires upstream social interventions
      that modify the environment in which obesity emerges. Recent studies have
      suggested that social capital and networks may influence a person's risk of
      obesity. Yet, few longitudinal studies have assessed whether social capital and
      networks reduce obesity risk in adult populations. In this study, the data come
      from three waves (2008, 2010, and 2013) of the Montreal Neighborhood Networks and
      Health Aging Panel (N=2606). Self-reported height and weight were used to
      calculate body mass index (BMI) with obesity defined as a BMI>30. Name and
      position generator instruments captured network measures of social capital,
      including: (1) upper reachability, (2) range, (3) diversity and (4) the number of
      kin ties. Questions on generalized trust and participation were used to assess
      cognitive and structural dimensions of social capital. Separate random effects
      logistic regression was used to examine the association among social network
      characteristics, social capital, and obesity. We found the greater the number of
      kin ties in a person's network, the greater the risk of obesity (OR: 1.33, 95%
      CI: 1.08-1.62). Adults with higher network diversity (OR: 0.83, 95% CI: 0.72
      0.96) and high generalized trust (OR: 0.52, 95% CI: 0.35-0.77) were at a lower
      the risk of obesity. The current study confirmed that higher network capital and
      trust were protective against obesity, while having kin ties was not.
      Disentangling the multidimensional role that social capital plays can lead to
      more effective interventions to reduce obesity.

PMID- 29197529
TI  - The longitudinal association between temperament and physical activity in young
      children.
AB  - OBJECTIVE: To examine the longitudinal association of negative affect and
      physical activity in a population of preschool children. STUDY DESIGN:
      Participants included 763 children (53% male) attending scheduled health
      supervision visits in their primary care physicians' offices. Data were collected
      at two time points at mean ages 27 (SD=5.4) and 47 (SD=6.2) months. Negative
      affect (NA) was measured using the Negative Affectivity (frustration/anger,
      decreased soothability) domain of the Children's Behavior Questionnaire. Physical
      Activity (PA) was assessed using a parent-report questionnaire. Multiple
      regression analyses tested the association between NA and PA, adjusting for child
      age, sex, z-BMI, PA at Time 1, maternal education, household income, and season,
      and examined for sex differences in the relationship between NA and PA. RESULTS:
      The longitudinal association between NA at Time 1 and PA at Time 2 was moderated
      by sex (p<0.001). After adjusting for covariates, females with greater NA at Time
      1 had decreased PA at Time 2 (p=0.01), whereas males with greater NA at Time 1
      had increased PA at Time 2 (p=0.01). Specifically, among females, every 1 unit
      increase in NA at Time 1 was associated with a 9.9min/day decrease in PA at Time
      2 (95% CI: -17.1, -2.8). CONCLUSIONS: NA and PA were associated early in
      childhood and the effects of NA on PA were gender specific. These findings
      underscore the importance of longitudinal and gender-specific analyses in mood
      obesity research.

PMID- 29197530
TI  - The neighborhood environment and obesity: Understanding variation by
      race/ethnicity.
AB  - Neighborhood characteristics have been associated with obesity, but less is known
      whether relationships vary by race/ethnicity. This study examined the
      relationship between soda consumption - a behavior strongly associated with
      obesity - and weight status with neighborhood sociodemographic, social, and built
      environments by race/ethnicity. We merged data on adults from the 2011-2013
      California Health Interview Survey, U.S. Census data, and InfoUSA (n=62,396).
      Dependent variables were soda consumption and weight status outcomes (body mass
      index and obesity status). Main independent variables were measures of three
      neighborhood environments: social (social cohesion and safety), sociodemographic
      (neighborhood socioeconomic status, educational attainment, percent Asian,
      percent Hispanic, and percent black), and built environments (number of grocery
      stores, convenience stores, fast food restaurants, and gyms in neighborhood). We
      fit multi-level linear and logistic regression models, stratified by individual
      race/ethnicity (NH (non-Hispanic) Whites, NH African Americans, Hispanics, and NH
      Asians) controlling for individual-level characteristics, to estimate
      neighborhood contextual effects on study outcomes. Lower neighborhood educational
      attainment was associated with higher odds of obesity and soda consumption in all
      racial/ethnic groups. We found fewer associations between study outcomes and the
      neighborhood, especially the built environment, among NH African Americans and NH
      Asians. While improvements to neighborhood environment may be promising to reduce
      obesity, null associations among minority subgroups suggest that changes,
      particularly to the built environment, may alone be insufficient to address
      obesity in these groups.

PMID- 29197531
TI  - Attitudes toward smokeless tobacco use at all public sports venues among U.S.
      adults, 2016.
AB  - Policies prohibiting smokeless tobacco (SLT) use at sports venues have been
      enacted in California and nine U.S. cities. We measured opposition toward SLT use
      at all public sports venues and its correlates among U.S. adults. Data were from
      the 2016 SummerStyles, a web-based survey of U.S. adults aged >=18years (n=4203).
      Weighted estimates of opposition ("strongly" or "somewhat") SLT use were computed
      overall and by selected characteristics. Multivariable Poisson regression
      analyses were performed to identify determinants of opposition toward SLT use
      overall and among current tobacco product users. Overall, 81.8% of U.S. adults
      opposed SLT use at all public sports venues. Opposition varied by tobacco product
      use status: 85.9%, 86.9% and 60.4% among never, former, and current tobacco
      product users, respectively. Among all adults, the likelihood of opposition was
      higher among females than males (Adjusted Prevalence Ratio [APR]=1.05; 95%CI=1.01
      1.08) and increased with every 10-year increase in age (APR=1.01; 95%CI=1.00
      1.02). Likelihood was lower among persons with a high school diploma (APR=0.92;
      95%CI=0.88-0.96) than those with college degree or higher; persons
      widowed/divorced/separated (APR=0.92; 95%CI=0.87-0.97) than those married; and
      current tobacco product users (APR=0.70; 95%CI=0.65-0.76) than never users. Among
      current tobacco product users, likelihood was lower among persons living in the
      Midwest (APR=0.81; 95%CI=0.66-0.98) and South (APR=0.78; 95%CI=0.65-0.94) than
      the Northeast. Most U.S. adults, including three-fifths of current tobacco
      product users, oppose SLT use at all public sports venues. Complete tobacco-free
      policies for sports venues that prohibit all forms of tobacco product use can
      help reduce the social acceptability of SLT use.

PMID- 29197532
TI  - Vascular risk factor burden and new-onset depression in the community.
AB  - Depression is associated with an increased likelihood of cardiac events and
      stroke. We hypothesized that the vascular risk factor burden might itself
      predispose to both cardiovascular events and depression. Therefore, we examined
      whether aggregate scores of vascular risk factor burden were associated with the
      new-onset of depression in the community. We studied 2023 depression- and
      dementia-free Framingham Heart Study (Framingham, USA) Offspring participants who
      attended both examination cycles 7 (1998-2001) and 8 (2005-2008). The American
      Heart Association Ideal Cardiovascular Health metric and the Framingham stroke
      risk profile were calculated at exam seven. New-onset depression was adjudicated
      at examination cycle eight as antidepressant medication use or Centre for
      Epidemiologic Studies Depression Scale scores >=16, after a mean follow-up of
      6.6years (standard deviation=0.7). Of the 2023 participants, 269 (13%) developed
      new-onset depression. Following adjustments for age, sex, education, and the time
      interval between baseline and follow-up, the odds of new-onset depression
      decreased by 10% for each one-point increase in ideal cardiovascular health
      scores (Odds Ratio [OR], 0.90; 95% confidence interval [CI] 0.81-0.99) and
      increased by 4% for each percentage point increase in the Framingham stroke risk
      profile (OR, 1.04; CI, 1.00-1.07). Results were not explained by interim clinical
      stroke or cerebral white matter injury. In conclusion, vascular risk factor
      burden was associated with the new onset of depression. Shared vascular risk
      factors may contribute to the increased risk of cardiovascular events observed in
      persons with depression.

PMID- 29197533
TI  - Cervical cancer screening uptake among HIV-positive women in Ontario, Canada: A
      population-based retrospective cohort study.
AB  - Cervical cancer caused by oncogenic types of the human papillomavirus (HPV) is of
      concern among HIV-positive women due to impairment of immune responses required
      to control HPV infection. Our objectives were to describe patterns of cervical
      cancer screening using Pap cytology testing among HIV-positive women in Ontario,
      Canada from 2008 to 2013 and to identify factors associated with adequate
      screening. We conducted a retrospective, population-based cohort study among
      screen-eligible HIV-positive women using provincial administrative health data.
      We estimated annual proportions tested and reported these with 95% confidence
      intervals (CI). Next, using person-years as the unit of analysis, we identified
      factors associated with annual Pap testing using log-binomial regression. A total
      of 2271 women were followed over 10,697 person-years. In 2008, 34.0% (95%CI 31.1
      37.0%) had a Pap test. By 2013, the proportion of HIV-positive women tested was
      25.9% (95%CI 23.6-28.2%). Women who were most likely to undergo testing were
      younger, were immigrants from countries with generalized HIV epidemics, lived in
      the highest income neighbourhoods, had a female primary care physician, had two
      or more encounters per year with an infectious disease or internal medicine
      specialist, and had greater comorbidity. Nearly three in four HIV-positive women
      were under-screened despite all having universal insurance for medically
      necessary services. Annual Pap testing decreased following the 2011-2013 release
      of new guidelines for a lengthened screen interval for average risk women and a
      billing disincentive. Clinic-based intervention such as physician alerts or
      reminders may be needed to improve screening coverage among HIV-positive women.

PMID- 29197534
TI  - Energy drinks and escalation in drug use severity: An emergent hazard to
      adolescent health.
AB  - The aim of the current study is to determine whether energy drink consumption
      contributes to drug use and, more specifically, an escalation in the severity of
      drug use. We first examine the association between energy drink use and hard drug
      use, and subsequently investigate whether soft drug use mediates this
      relationship. Potential moderating influences are also investigated by testing
      whether the degree of mediation varies by age, gender, and race. The current
      study uses a nationally representative sample of 8th (ages 13-14), 10th (ages 15
      16), and 12th (ages 17-18) grade adolescents from the 2015 Monitoring the Future
      survey. Negative binomial regression is employed to examine associations between
      energy drink consumption and soft and hard drug use. Mediation results indicate
      that energy drink consumption is significantly associated with increased soft
      drug use, which is, in turn, associated with significant increases in hard drug
      use. This cascading effect of energy drink consumption on drug use appears to be
      stronger among younger females and older males. Results for the moderating effect
      of race are mixed. Energy drinks appear to pose an important threat to adolescent
      health in the form of soft and hard drug use. The United States may want to
      consider adopting energy drink policies similar to European countries and Canada,
      which require warning labels on beverages with high caffeine content.

PMID- 29197535
TI  - Driving under the influence behaviours among high school students who mix alcohol
      with energy drinks.
AB  - Alcohol and energy drinks are commonly used substances by youth in Canada, and
      are often mixed (AmED). While several studies have shown that AmED can have
      dangerous effects, less well understood is how AmED is associated with driving
      under the influence of either alcohol or drugs. This study sought to determine
      whether youth who use AmED were more likely to engage in driving, or being a
      passenger of a driver, under the influence of alcohol or cannabis compared to
      youth who use either alcohol or energy drinks alone. This study used data from
      grade 10-12 students who took part in the 2014/2015 Canadian Student Tobacco,
      Alcohol and Drugs Survey (N=17,450). The association of past-year AmED use with
      past-30day: driving under the influence of alcohol or cannabis, and riding with
      an alcohol- or cannabis-influenced driver, was assessed using logistic
      regression. One in four youth had consumed AmED in the previous 12months. AmED
      users were more likely to engage in all risk behaviours except riding with a
      drinking driver, relative to youth who only consumed alcohol. No association was
      observed for youth who consumed alcohol and energy drinks on separate occasions.
      Youth who use AmED demonstrate a higher risk profile for driving under the
      influence of alcohol or cannabis, than youth who use alcohol alone. Future
      research should explore the biopsychosocial pathways that may explain why using
      energy drinks enhances the already heightened risk posed by alcohol on other
      health-related behaviours such as driving under the influence.

PMID- 29197536
TI  - Do school physical activity policies and programs have a role in decreasing
      multiple screen time behaviours among youth?
AB  - Screen time in youth has been associated with a wide range of poor health
      outcomes. Evidence indicates the need to develop physical activity (PA) school
      policies and programs that are aimed at decreasing youth screen time behaviours.
      This study aims to understand the association between PA policies and programs
      embedded into the functioning of 89 schools across two provinces in Canada and
      multiple screen time behaviours. As part of the COMPASS Study, a total of 44,861
      youth aged between 13 and 18years and belonging to 89 schools in two Canadian
      provinces completed a validated questionnaire for health behaviours and outcomes
      data. PA policies and programs were measured using the School Policies and
      Practices Questionnaire, completed by the relevant school administrator.
      Participation in before-school, noon hour, or after-school intramural programs,
      participation in varsity sports, and access to indoor areas of PA during non
      instructional time, was associated with significantly lower multiple screen time
      behaviours across both provinces. With exposure to multiple electronic and
      digital devices only predicted to increase among youth in the future, there is a
      need to conceptualize and integrate school-based screen time reducing PA policies
      and programs into the regular functioning of the schools.

PMID- 29197537
TI  - Letter to the editor.

PMID- 29197538
TI  - Orbital Frontal Nerve Schwannoma-Distinctive Radiological Features.
AB  - PURPOSE: To review the radiological findings of frontal nerve schwannoma of the
      orbit and determine distinguishing imaging features. DESIGN: Retrospective
      interventional case series. METHODS: Setting: Single tertiary institution.
      PERIOD: September 1996 to December 2016. PATIENT POPULATION: Thirteen patients
      with orbital frontal nerve schwannoma. INTERVENTION: Patients underwent surgical
      excision following preoperative imaging. MAIN OUTCOME MEASURES: Imaging
      characteristics on computed tomography (CT) and magnetic resonance imaging (MRI).
      RESULTS: There were 13 patients with histopathologically proven schwannoma of the
      frontal nerve. Mean age was 44.4 years and 61.5% were male. The majority (84.6%)
      of frontal nerve schwannomas extended between the supraorbital notch and superior
      orbital fissure. The most common shape seen in our patients with frontal nerve
      schwannoma was a multilobulated "beaded" appearance (46.2%), followed by a
      dumbbell (30.8%), oval (15.4%), and fusiform (7.7%) shape. On CT imaging, all
      patients had bony remodeling. Target sign, fascicular sign, and cystic
      degeneration were seen in 76.9%, 35.8%, and 46.2% of patients, respectively. On
      radiological-pathologic correlation, the zone of tightly packed cellular solid
      portion (Antoni A pattern) corresponded to the hypointense area on T2-weighted
      MRI and the hyperintense area on gadolinium-enhanced T1-weighted MRI. CONCLUSION:
      Frontal nerve schwannoma should be considered as a differential diagnosis for any
      superior orbital mass. Our study describes several radiological findings that
      would point toward its diagnosis, including its multilobulated beaded or dumbbell
      shape, as well as additional signs such as the target sign, fascicular sign, and
      cystic degeneration.

PMID- 29197539
TI  - Stress response pathways, appetite regulation, and drug addiction.

PMID- 29197540
TI  - Miscellaneous lanostane triterpenoids with cytotoxicities from fruiting bodies of
      the basidiomycete Stereum sp.
AB  - Ten new highly oxygenated lanostane triterpenoids, stereinones A-J (1-10), were
      isolated from the fruiting bodies of the basidiomycete Stereum sp. Compounds 3
      and 4 are structurally characterized as intact lanostane-type triterpenoids
      containing unusual 1,2-diketone functionality at C-11 and C-12, while compound 10
      is a 24-methylene-lanostane. The structures of these new compounds were
      established based on detailed 1D and 2D NMR spectroscopic analyses, along with
      quantum chemical NMR calculations. All isolates were evaluated for their in vitro
      cytotoxicities against five human tumor cell lines (including HL-60, A-549, SMMC
      7721, MCF-7, and SW480 cell lines). Compound 4 showed moderate cytotoxic
      activities against tumor cell lines SMMC-7721 and SW480 with IC50 values of 9.1
      and 9.8MUM, respectively.

PMID- 29197541
TI  - Structural identification and biological activity of six new Shellolic esters
      from Lac.
AB  - Six new sesquiterpenoid esters, named Shellolic ester A-F (1-6), along with four
      known Lac dyes (7-10) were isolated from methanol extract of the secretions of
      Laccifer lacca. Their structures were established on the basis of spectroscopic
      analyses (IR, HR-ESI-MS, 1D and 2D NMR) and by comparison with published data.
      Biological activities evaluation of the isolates showed that they were inactive
      against human cancer cell lines (HepG2, MCF-7, Hela and C6) and LPS-treated
      RAW264.7, which is well consistent with that Lac resin used as nontoxic material
      in agriculture applications, pharmaceutical formulations, and food additives.
      However, compound 2, 4, 7, 9, 10 were found to be considerable active against B.
      subtilis, E. coli, and S. aureus microorganisms. The results complements the
      current knowledge about Lac produced from China. Meanwhile, Our present study
      further reveals that Lac resin are edible with no toxicity and physiologically
      harmless at the level employed as an excipient.

PMID- 29197542
TI  - Tomenphantadenine, an unprecedented germacranolide-adenine hybrid heterodimer
      from the medicinal plant Elephantopus tomentosus L.
AB  - An unusual adenine-substituted germacrane sesquiterpene lactone,
      tomenphantadenine (1), has been isolated from the whole plant of Elephantopus
      tomentosus L. The structure of this compound was established by comprehensive
      spectroscopic analysis including high resolution (HR) ESI-MS, 1D and 2D nuclear
      magnetic resonance (NMR) spectroscopic data. This compound features novel hybrid
      pattern of germacrane sesquiterpene with adenine through C-N linkage, and a
      possible biosynthetic pathway for it was proposed. Compound 1 showed potent
      antibacterial activity against the gram-positive Staphylococcus aureus and weak
      acetylcholinesterase (AChE) inhibitory activity.

PMID- 29197543
TI  - Role of dopamine D1 receptor in 3-fluoromethamphetamine-induced neurotoxicity in
      mice.
AB  - 3-Fluoromethamphetamine (3-FMA) is an illegal designer drug of methamphetamine
      (MA) derivative. Up to date, little is known about the neurotoxic potential of 3
      FMA. In the present study, we investigated the role of dopamine receptors in
      neurotoxicity induced by 3-FMA in comparison with MA (35 mg/kg, i.p.) as a
      control drug. Here we found that 3-FMA (40, 60 or 80 mg/kg, i.p.) produced
      mortality in a dose-dependent manner in mice. Treatment with 3-FMA (40 mg/kg,
      i.p.) resulted in significant hyperthermia, oxidative stress and microgliosis
      (microglial differentiation into M1 phenotype) followed by pro-apoptotic changes
      and the induction of terminal deoxynucleotidyl transferase dUDP nick end labeling
      (TUNEL)-positive cells. Moreover, 3-FMA significantly produced dopaminergic
      impairments [i.e., increase in dopamine (DA) turnover rate and decreases in DA
      level, and in the expression of tyrosine hydroxylase (TH), dopamine transporter
      (DAT), and vesicular monoamine transporter 2 (VMAT-2)] with behavioral
      impairments. These dopaminergic neurotoxic effects of 3-FMA were comparable to
      those of MA. SCH23390, a dopamine D1 receptor antagonist, but not sulpiride, a
      dopamine D2 receptor antagonist significantly attenuated 3-FMA-induced
      neurotoxicity. Although both SCH23390 and sulpiride attenuated MA-induced
      dopaminergic neurotoxicity, sulpiride is more effective than SCH23390 on the
      dopaminergic neurotoxicity. Interestingly, SCH23390 treatment positively
      modulated 3-FMA-induced microglial activation (i.e., SCH23390 inhibited M1
      phenotype from 3-FMA insult, but activated M2 phenotype). Therefore, our results
      suggest that the activation of dopamine D1 receptor is critical to 3-FMA-induced
      neurotoxicity, while both dopamine D1 and D2 receptors (dopamine D2 receptor >
      dopamine D1 receptor) mediate MA-induced dopaminergic neurotoxicity.

PMID- 29197544
TI  - Control of microbial sulfide production by limiting sulfate dispersal in a water
      injected oil field.
AB  - Oil production by water injection often involves the use of makeup water to
      replace produced oil. Sulfate in makeup water is reduced by sulfate-reducing
      bacteria to sulfide, a process referred to as souring. In the MHGC field souring
      was caused by using makeup water with 4mM (384ppm) sulfate. Mixing with sulfate
      free produced water gave injection water with 0.8mM sulfate. This was amended
      with nitrate to limit souring and was then distributed fieldwide. The start-up of
      an enhanced-oil-recovery pilot caused all sulfate-containing makeup water to be
      used for dissolution of polymer, which was then injected into a limited region of
      the field. Produced water from this pilot contained 10% of the injected sulfate
      concentration as sulfide, but was free of sulfate. Its use as makeup water in the
      main water plant of the field caused injection water sulfate to drop to zero.
      This in turn strongly decreased produced sulfide concentrations throughout the
      field and allowed a decreased injection of nitrate. The decreased injection of
      sulfate and nitrate caused major changes in the microbial community of produced
      waters. Limiting sulfate dispersal into a reservoir, which acts as a sulfate
      removing biofilter, is thus a powerful method to decrease souring.

PMID- 29197546
TI  - Prevalence of Arnold Nerve Reflex in Adults and Children With Chronic Cough.
AB  - BACKGROUND: Cough originates from stimulation of structures innervated by the
      vagus nerve, including the airways and distal esophagus. Arnold nerve reflex
      describes the induction of cough by stimulation of the external auditory canal,
      which is innervated by the auricular branch of the vagus. Historically, the
      prevalence of this reflex has been reported in the range of 2% to 3% on the basis
      of studies of outpatients in otolaryngology practices, but has not been
      investigated in healthy volunteers or in patients with chronic cough. METHODS:
      Two hundred adults and 100 children with chronic cough, as well as 100 adult and
      100 pediatric volunteers, underwent evaluation consisting of stimulation of the
      external auditory canal of each ear with a cotton-tipped applicator. Cough
      occurring within 10 seconds of stimulation was considered induced by the
      intervention. RESULTS: Arnold nerve reflex was present in 25.5% of adults and 3%
      of children with chronic cough. The prevalence of the reflex was 2% among healthy
      adults and children. In adults with chronic cough, Arnold nerve reflex was
      observed more commonly in women (31.6%) than men (12.5%) and was unilateral in
      the majority of patients (90.2%). CONCLUSIONS: The greater than 12 fold
      prevalence of Arnold nerve reflex in adults with chronic cough compared with
      healthy volunteers supports the concept of cough hypersensitivity syndrome (CHS),
      in which vagal hypersensitivity is proposed to underlie chronic refractory cough.
      The absence of increased prevalence among children with chronic cough suggests
      that cough hypersensitivity syndrome is an acquired condition, perhaps triggered
      by viral respiratory infection or other environmental factor.

PMID- 29197545
TI  - Potential cancer chemopreventive and anticancer constituents from the fruits of
      Ficus hispida L.f. (Moraceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hispida L.f. (Moraceae) has been used as
      alternative for traditional medicine in the treatment of various ailments
      including cancer-cure. The aim of this study was to evaluate the cancer
      chemopreventive and anticancer activities of crude extracts of F. hispida, with
      the objective to screen the inhibition of Epstein-Barr virus early antigen, and
      cytotoxic active components, and provide foundation for potential applications of
      this promising medical plant. MATERIALS AND METHODS: Compounds were isolated from
      the MeOH extract of F. hispida fruits, and their structure elucidation was
      performed on the basis of extensive spectroscopic analysis. The isolated
      compounds were evaluated for their inhibitory activities against the Epstein-Barr
      virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13
      acetate (TPA) in Raji cells, and cytotoxic activities against human cancer cell
      lines (HL60, A549, SKBR3, KB, Hela, HT29, and HepG2) and a normal cell (LO2)
      using MTT method. For the compound with potent cytotoxic activity, its apoptosis
      inducing activity was evaluated by the observation of ROS generation level
      expression, and membrane phospholipid exposure and DNA fragmentation in flow
      cytometry. The mechanisms of the apoptosis induction were analyzed by Western
      blotting. RESULTS: Nineteen compounds, 1-19, including two new isoflavones, 3'
      formyl-5,7-dihydroxy-4'-methoxyisoflavone (2) and 5,7-dihydroxy-4'-methoxy-3'- (3
      methyl-2-hydroxybuten-3-yl)isoflavone (3), were isolated from the MeOH extract of
      F. hispida fruits. Five compounds, isowigtheone hydrate (1), 2, 3, 9, and 19,
      showed potent inhibitory effects on EBV-EA induction with IC50 values in the
      range of 271-340 molar ratio 32 pmol-1 TPA. In addition, five phenolic compounds,
      1-3, 10, and 13, exhibited cytotoxic activity against two or more cell lines
      (IC50 2.5-95.8MUM), as well as compounds 1 and 3 were also displayed high
      selectivity for LO2/HepG2 (SI 23.5 and 11.8, respectively), while the compound 1
      induced ROS generation leads to activated caspases-3, -8, and -9 apoptotic
      process in HL60 cells. CONCLUSION: This study has established that the MeOH
      extract of F. hispida fruits contains isoflavones, coumarins, caffeoylquinic
      acids, along with other compounds including phenolics and steroid glucoside as
      active principles, and has demonstrated that the chemical constituents of F.
      hispida may be valuable as potential chemopreventive and anticancer agents.

PMID- 29197547
TI  - Further Studies of Unsuspected Emphysema in Nonsmoking Patients With Asthma With
      Persistent Expiratory Airflow Obstruction.
AB  - BACKGROUND: Previously, we and other investigators have described reversible loss
      of lung elastic recoil in patients with acute and persistent, moderate-to-severe,
      chronic, treated asthma who never smoked, and its adverse effect on maximal
      expiratory airflow. In four consecutive autopsies, we reported the
      pathophysiologic mechanism(s) has been unsuspected mild, diffuse, middle and
      upper lobe centrilobular emphysema. METHODS: We performed prospective studies (5
      to 22 years) in 25 patients (12 female) with chronic asthma, age 55 +/- 15 years,
      who never smoked, with persistent moderate-to-severe expiratory obstruction.
      Studies included measuring blood eosinophils, IgE, total exhaled nitric oxide
      (NO), central airway NO flux, peripheral airway/alveolar NO concentration,
      impulse oscillometry, heliox curves, lung elastic recoil, and high-resolution
      thin-section (1 mm) lung CT imaging at full inspiration with voxel
      quantification. RESULTS: In 25 patients with stable asthma with varying type 2
      phenotype, after 270 MUg of aerosolized albuterol sulfate had been administered
      with a metered dose inhaler with space chamber, FVC was 3.1 +/- 1.0 L (83% +/-
      13% predicted) (mean +/- SD), FEV1 was 1.8 +/- 0.6 L (59% +/- 11%), the FEV1/FVC
      ratio was 59% +/- 10%, and the ratio of single-breath diffusing capacity of the
      lung for carbon monoxide to alveolar volume was 4.8 +/- 1.1 mL/min/mm Hg/L (120%
      +/- 26%). All 25 patients with asthma had loss of static lung elastic recoil
      pressure, which contributed equally to decreased intrinsic airway conductance in
      limiting expiratory airflow. Lung CT scanning detected none or mild emphysema. In
      all four autopsied asthmatic lungs previously reported and one unreported
      explanted lung, microscopy revealed unsuspected mild, diffuse centrilobular
      emphysema in the upper and middle lung fields, and asthma-related remodeling in
      airways. In eight cases, during asthma remission, there were increases in
      measured static lung elastic recoil pressure-calculated intrinsic airway
      conductance, and measured maximal expiratory airflow at effort-independent lung
      volumes. CONCLUSIONS: As documented now in five cases, unsuspected microscopic
      mild centrilobular emphysema is the sentinel cause of loss of lung elastic
      recoil. This contributes significantly to expiratory airflow obstruction in never
      smoking patients with asthma, with normal diffusing capacity and near-normal lung
      CT scan results. TRIAL REGISTRY: Protocol No. 20070934 and Study No. 1090472,
      Western Institutional Review Board, Olympia, WA; ClinicalTrials.gov; No.
      NCT00576069; URL: www.clinicaltrials.gov.

PMID- 29197548
TI  - Right Heart Dysfunction in Heart Failure With Preserved Ejection Fraction: The
      Impact of Atrial Fibrillation.
AB  - BACKGROUND: Right ventricular (RV) dysfunction and atrial fibrillation (AF)
      frequently coexist in heart failure with preserved ejection fraction (HFpEF). The
      mechanisms underlying the association between AF and RV dysfunction are
      incompletely understood. METHODS AND RESULTS: We identified 102 patients. RV
      function was assessed with the use of multiple echocardiographic parameters, and
      dysfunction was present if >=2 parameters were below the recommended cutoffs. RV
      function, right atrial (RA) reservoir strain, and RA emptying fraction were
      compared between AF and sinus rhythm. We included 91 patients with sufficient
      echocardiographic quality: 45 (50%) had no history of AF, 14 (15%) had earlier AF
      while in sinus rhythm, and 32 (35%) had current AF. The prevalence of RV
      dysfunction varied across subgroups (never AF, earlier AF, and current AF: 20%,
      43% and 63%, respectively; P = .001). AF was associated with RV dysfunction (odds
      ratio [OR] 4.70 [95% confidence interval [CI] 1.82-12.1]; P = .001) independently
      from pulmonary pressures. In patients in sinus rhythm with earlier AF, RA
      emptying fraction was lower compared with patients without AF history (41 vs 60%;
      P = .002). Earlier AF was also associated with reduced RA reservoir strain (OR
      4.57 [95% CI 1.05-19.9]; P = .04) independently from RV end-diastolic pressure.
      CONCLUSIONS: Atrial fibrillation is strongly related to reduced RV and RA
      function in HFpEF independently from pulmonary pressures.

PMID- 29197549
TI  - Isolation and characterization of Kabuto Mountain virus, a new tick-borne
      phlebovirus from Haemaphysalis flava ticks in Japan.
AB  - In Japan, indigenous tick-borne phleboviruses (TBPVs) and their associated
      diseases first became evident in 2013 by reported human cases of severe fever
      with thrombocytopenia syndrome (SFTS). In this study, we report a novel member of
      the genus Phlebovirus designated as Kabuto Mountain virus (KAMV), which was
      isolated from the ixodid tick Haemaphysalis flava in Hyogo, Japan. A complete
      viral genome sequencing and phylogenetic analyses showed that KAMV is a novel
      member of TBPVs, which is closely related to the Uukuniemi and Kaisodi group
      viruses. However, unlike the Uukuniemi group viruses, the 165-nt intergenic
      region (IGR) in the KAMV S segment was highly C-rich in the genomic sense and not
      predicted to form a secondary structure, which are rather similar to those of the
      Kaisodi group viruses and most mosquito/sandfly-borne phleboviruses. Furthermore,
      the NSs protein of KAMV was highly divergent from those of other TBPVs. These
      results provided further insights into the genetic diversity and evolutionary
      relationships of TBPVs. KAMV could infect and replicate in some rodent and
      primate cell lines. We evaluated the infectivity and pathogenicity of KAMV in
      suckling mice, where we obtained a virulent strain after two passages via
      intracerebral inoculation. This is the first report showing the existence of a
      previously unrecognized TBPV in Japan, other than the SFTS virus.

PMID- 29197550
TI  - Reduced intensity is preferred over myeloablative conditioning allogeneic HCT in
      chronic lymphocytic leukemia whenever indicated: A systematic review/meta
      analysis.
AB  - Despite availability of new and more effective therapies for chronic lymphocytic
      leukemia, presently this disease remains incurable unless eligible patients are
      offered an allogeneic hematopoietic cell transplant. Recent published clinical
      practice recommendations on behalf of the American Society for Blood and Marrow
      Transplantation relegated the role of for allogeneic hematopoietic cell
      transplantation to later stages of the disease. To our knowledge, no randomized
      controlled trial has been performed to date comparing myeloablative versus
      reduced intensity conditioning regimens in chronic lymphocytic leukemia patients
      eligible for the procedure. We performed a systematic review/meta-analysis to
      assess the efficacy of allogeneic hematopoietic cell transplantation when using
      myeloablative or reduced intensity conditioning regimens. We report the results
      in accordance to the Preferred Reporting Items for Systematic Reviews and Meta
      analyses guidelines. Based on lower non-relapse mortality and slightly better
      overall survival rates, reduced intensity conditioning regimens appear to be the
      most desirable choice whenever the procedure is indicated for this disease. It
      appears highly unlikely that a RCT will be ever performed comparing reduced
      intensity vs. myeloablative allogeneic hematopoietic cell transplantation in
      chronic lymphocytic leukemia. In the absence of such a study, results of this
      systematic review/meta-analysis represent the best available evidence supporting
      this recommendation whenever indicated in patients with chronic lymphocytic
      leukemia.

PMID- 29197552
TI  - MeHg affects the activation of FAK, Src, Rac1 and Cdc42, critical proteins for
      cell movement in PDGF-stimulated SH-SY5Y neuroblastoma cells.
AB  - Methylmercury (MeHg) is an environmental neurotoxicant that inhibits neuronal
      migration. This process requires several cyclic steps involving the formation of
      membrane protrusions (lamellipodia and filopodia) and focal adhesion turnover.
      FAK and Src are critical proteins that regulate both processes. The FAK-Src
      complex promotes the activation of Rac1 and Cdc42, two GTPases involved in the
      remodeling of the actin cytoskeletal network. Here, we studied the effect of MeHg
      (1, 10, 100, 500 and 1000nM) on cell migration, the formation of cell
      protrusions, focal adhesion location and the activation of FAK, Src, Rac1 and
      Cdc42 using the SH-SY5Y neuroblastoma cell line stimulated with PDGF-BB (PDGF).
      The data show that MeHg (1-500nM) inhibited PDGF-stimulated cell migration. In
      PDGF-stimulated cells, MeHg (100-1000nM) decreased protrusions and increased the
      size of the p-FAKY397 clusters. MeHg also inhibited PDGF-induced FAK and Src
      activation and, at 100nM, MeHg inhibited the activation of Rac1 and Cdc42.
      Altogether, the findings show that low concentrations of MeHg inhibit SH-SY5Y
      cell migration by disrupting the activation and disassembly of FAK. This
      negatively affects the activation of Src, Rac1 and Cdc42, all of which are
      critical proteins for the regulation of cell movement. These effects could be
      related to the MeHg-mediated inhibition of PDGF-induced formation of lamellipodia
      and filopodia, focal adhesion disassembly and PDGF-induced movement.

PMID- 29197551
TI  - Allelic variants of the aryl hydrocarbon receptor differentially influence UVB
      mediated skin inflammatory responses in SKH1 mice.
AB  - The mouse strain SKH1 is widely used in skin research due to its hairless
      phenotype and intact immune system. Due to the complex nature of aryl hydrocarbon
      receptor (AHR) function in the skin, the development of additional in vivo models
      is necessary to study its role in cutaneous homeostasis and pathology. Variants
      of the Ah allele, exist among different mouse strains. The Ahb-1 and Ahd alleles
      express high and low affinity ligand binding forms of the AHR, respectively. The
      outbred SKH1 mice express the Ahb-2 and/or Ahd alleles. SKH1 mice were crossed
      with C57BL/6J mice, which harbor the Ahb-1 allele, to create useful models for
      studying endogenous AHR function. SKH1 mice were bred to be homozygous for either
      the Ahb-1 or Ahd allele to establish strains for use in comparative studies of
      the effects of differential ligand-mediated activation through gene expression
      changes upon UVB exposure. Ahb-1 or Ahd allelic status was confirmed by DNA
      sequence analysis. We tested the hypothesis that SKH1-Ahb-1 mice would display
      enhanced inflammatory signaling upon UVB exposure compared to SKH1-Ahd mice.
      Differential basal AHR activation between the strains was determined by assessing
      Cyp1a1 expression levels in the small intestine, liver, and skin of the SKH1-Ahb
      1 mice compared to SKH1-Ahd mice. To determine whether SKH1-Ahb-1 mice are more
      prone to a pro-inflammatory phenotype in response to UVB, gene expression of
      inflammatory mediators was analyzed. SKH1-Ahb-1 mice expressed enhanced gene
      expression of the chemotactic factors Cxcl5, Cxcl1, and Ccl20, as well as the
      inflammatory signaling factors S100a9 and Ptgs2, compared to SKH1-Ahd mice in
      skin. These data supports a role for AHR activation and enhanced inflammatory
      signaling in skin.

PMID- 29197553
TI  - Evidence for condition mediated trade-offs between the HPA- and HPG-axes in the
      wild zebra finch.
AB  - Opportunistic breeding is a strategy used to maximize reproductive success in
      unpredictable environments. Birds that breed opportunistically are thought to
      maintain partial activation of the reproductive axis in order to rapidly initiate
      breeding when environmental conditions become suitable. The physiological
      mechanisms that modulate reproduction in seasonally breeding birds have been well
      explored. In contrast, the physiological mechanisms that allow opportunistic
      breeding birds to maintain a continued state of reproductive readiness has not
      been well established. Here, we tested the hypothesis that reproductive readiness
      is modulated through condition-mediated effects on the hypothalamic
      pituitaryadrenal (HPA) axis and its downstream effects on corticosterone (CORT)
      secretion in wild zebra finches (Taeniopygia guttata). We examined the variation
      in body condition, HPA-axis activity (endogenous and adrenocorticotropic hormone
      (ACTH)-induced responses), and hypothalamic-pituitary-gonadal (HPG) axis activity
      activity (baseline and gonadotropin-releasing hormone (GnRH) induced testosterone
      and estradiol levels) in zebra finches across five sites in the Northern
      Territory in Australia. We found that birds at the sites in the lowest condition
      had the highest level of baseline and peak CORT. Additionally, males at the sites
      in the lowest condition had the highest fold increase in testosterone following a
      GnRH challenge. Across sites, birds with low body condition had high baseline,
      peak, and ACTH-induced levels of CORT. Our data suggest that reproductive
      readiness in opportunistically breeding birds is modulated by condition-mediated
      trade-offs between the HPA- and the HPG-axes. Further work is needed to
      understand the environmental conditions that influence reproductive activation in
      opportunistically breeding birds.

PMID- 29197554
TI  - Baseline and stress-induced blood properties of male and female Darwin's small
      ground finch (Geospiza fuliginosa) of the Galapagos Islands.
AB  - Birds are renowned for exhibiting marked sex-specific differences in activity
      levels and reproductive investment during the breeding season, potentially
      impacting circulating blood parameters associated with stress and energetics.
      Males of many passerines often do not incubate, but they experience direct
      exposure to intruder threat and exhibit aggressive behaviour during the nesting
      phase in order to defend territories against competing males and predators.
      Nesting females often have long bouts of inactivity during incubation, but they
      must remain vigilant of the risks posed by predators and conspecific intruders
      approaching the nest. Here, we use 33 free-living male (n = 16) and female (n =
      17) Darwin's small ground finches (Geospiza fuliginosa) on Floreana Island
      (Galapagos Archipelago) to better understand how sex-specific roles during the
      reproductive period impact baseline and stress-induced levels of plasma
      corticosterone (CORT), blood glucose and haematocrit. Specifically, we
      hypothesise that males are characterised by higher baseline values given their
      direct and relatively frequent exposure to intruder threat, but that a
      standardised stress event (capture and holding) overrides any sex-specific
      differences. In contrast with expectations, baseline levels of all blood
      parameters were similar between sexes (13.4 +/- 1.9 ng ml-1 for CORT, 13.7 +/-
      0.4 mmol l-1 for glucose, 58.3 +/- 0.8% for haematocrit). Interestingly, females
      with higher body condition had lower baseline haematocrit. All blood parameters
      changed with time since capture (range 1.2-41.3 min) in both sexes, whereby CORT
      increased linearly, haematocrit decreased linearly, and glucose increased to a
      peak at ~20 min post-capture and declined to baseline levels thereafter. Our
      results do not support the hypothesis that sex-specific roles during the
      reproductive period translate to differences in blood parameters associated with
      stress and energetics, but we found some evidence that blood oxygen transport
      capacity may decline as finches increase in body condition.

PMID- 29197555
TI  - Temperature- vs. estrogen-induced sex determination in Caiman latirostris
      embryos: Both females, but with different expression patterns of key molecules
      involved in ovarian development.
AB  - Caiman latirostris is a species with temperature dependent sex determination
      (TSD), which implies that the incubation temperature of the eggs is the main
      factor that determines the sex during a thermo-sensitive period (TSP). However,
      estrogens play a critical role in this process. The administration of 17beta
      estradiol (E2) previous to TSP overrides the effects of male incubation
      temperature, producing phenotypic females. This effect has been defined as sex
      reversal or estrogen-induced sex determination (E2SD). The aim of the present
      study is to describe similarities and differences in the effects of TSD and E2SD
      treatment conditions on ovary development. Our results show that the two
      treatment conditions studied are able to produce different ovaries. Treatment
      with E2 modified the expression pattern of estrogen receptor alpha and
      progesterone receptor, and expression of the enzyme aromatase. Moreover, in E2SD
      females, the proliferation/apoptosis dynamic was also altered and high expression
      of TAp63 was observed suggesting the presence of greater DNA damage in germ
      cells. To the best of our knowledge, this is the first report that describes the
      morphology of the female gonad of C. latirostris in three stages of embryonic
      development and shows the expression of TAp63 during the gonad development of a
      reptile. It is important to emphasize that the changes demonstrated in E2SD
      female gonads of embryos show that environmental compounds with proven estrogenic
      activity alter the follicular dynamics of C. latirostris in neonatal as much as
      in juvenile animals, endangering their reproductive health and possibly bringing
      consequences to ecology and evolution.

PMID- 29197556
TI  - miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1
      cells via targeting RAF-1.
AB  - BACKGROUND: Recent reports have demonstrated that RAF-1L613V (a mutant of RAF-1)
      mutant mice show bone deformities similar to Noonan syndrome. It has been
      suggested that RAF-1L613V might abnormally activate osteoblast differentiation of
      MC3T3-E1 cells. METHODS: To demonstrate that RAF-1 is associated with bone
      deformity and that RAF-1L613V dependent bone deformity could be inhibited by
      microRNA-195 (miR-195), we first investigated the amplifying influence of wild
      type RAF-1 (WT) or RAF-1L613V (L613V) on the viability and differentiation of
      MC3T3-E1 cells induced by bone morphogenetic protein-2 (BMP-2) via 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline
      phosphatase (ALP) and Alizarin Red S (ARS) staining, quantitative real-time
      polymerase chain reaction (qRT-PCR) and western blot analysis. Subsequently, we
      investigated the blocking effect and its mechanism of miR-195 for abnormal
      activation of osteoblast differentiation of MC3T3-E1 cells via targeting RAF-1.
      RESULTS: RAF-1, especially RAF-1L613V, abnormally activates osteoblast
      differentiation of MC3T3-E1 cells induced by BMP-2. Meanwhile, miR-195 could
      inhibit the cell viability and differentiation of MC3T3-E1 cells. Transfection of
      miR-195 largely suppressed the L613V-induced viability and osteoblast
      differentiation of MC3T3-E1 cells and attenuated the accelerative effect of L613V
      on runt-related transcription factor-2 (Runx2), Osterix (OSX), alkaline
      phosphatase (ALP), osteocalcin (OCN), and distal-less homeobox 5 (DLX5)
      osteogenic gene expressions. In addition, miR-195 decreased the expression of RAF
      1 mRNA and protein by directly targeting the 3'-untranslated regions (3'-UTR) of
      RAF-1 mRNA in MC3T3-E1 cells. CONCLUSIONS: Our findings indicated that miR-195
      inhibited WT and L613V RAF-1 induced hyperactive osteoblast differentiation in
      MC3T3-E1 cells by targeting RAF-1. miR-195 might be a novel therapeutic agent for
      the treatment of L613V-induced bone deformity in Noonan syndrome.

PMID- 29197557
TI  - Soy flour as an alternative to purified lipoxygenase for the enzymatic synthesis
      of resolvin analogues.
AB  - Specialized pro-resolving mediators are lipid signaling molecules synthesized
      from omega-3 and -6 polyunsaturated fatty acids, which promote the resolution of
      the inflammatory response. They are potential drug targets for the treatment of
      numerous conditions linked with uncontrolled inflammation. Many of these
      mediators can be effectively synthesized using enzymes, such as lipoxygenases.
      However, these enzymes are expensive to purchase and can be difficult to isolate.
      In this work, we show that commercial soy flour can be used directly as a source
      of lipoxygenase for the biosynthesis of specialized pro-resolving mediators from
      DHA and other biologically important fatty acids. The reaction was optimized and
      the products characterized. We found that the reaction yield and products were
      comparable to those synthesized using a commercial 15-lipoxygenase preparation.

PMID- 29197558
TI  - Clinical utility of an ultrasensitive late night salivary cortisol assay by
      tandem mass spectrometry.
AB  - BACKGROUND: Late night salivary cortisol measurement is a clinically important
      and convenient screening test for Cushing's syndrome. Tandem mass spectrometry
      (LC-MS/MS) assays have superior sensitivity and specificity compared to
      immunoassays. Our goal was to improve a LC-MS/MS method to measure salivary
      cortisol in both adult and pediatric patients and to characterize its analytical
      performance by method validation and clinical performance by chart review.
      METHODS: We improved a LC-MS/MS method originally developed for urine cortisol to
      measure low level salivary cortisol. The sample preparation was by liquid-liquid
      extraction using dichloromethane followed by stepwise washing with acidic, basic
      and neutral solutions. The assay's analytical performance was characterized and
      retrospective patient chart review was conducted to evaluate the assay's clinical
      diagnostic performance. RESULTS: The LC-MS/MS assay showed enhanced functional
      sensitivity of 10 ng/dL for salivary cortisol and was linear within an analytical
      measurement range of 10-10,000 ng/dL. Assay accuracy was within 84-120% as
      determined by recovery studies and correlation with a reference method. Data from
      healthy adult volunteers was compiled to establish the reference interval for
      late night salivary cortisol. Patient chart review determined subjects with
      diagnosis of Cushing's syndrome or disease, and assay's clinical diagnostic
      sensitivity of 100% and specificity of 92% when the cutoff value was 70 ng/dL.
      CONCLUSIONS: The improved LC-MS/MS method is sensitive and specific with enhanced
      analytical performance and clinical diagnostic utility for screening Cushing's
      syndrome. The assay may have broad clinical application due to its high
      sensitivity and wide dynamic range.

PMID- 29197560
TI  - Pentraxin-3 and coronary artery disease.

PMID- 29197559
TI  - Disruption of Semantic Network in Mild Alzheimer's Disease Revealed by Resting
      State fMRI.
AB  - Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients
      even in the early stages of the illness. In this work, we tested the hypothesis
      that the semantic control network is deregulated in mild AD patients. We assessed
      the integrity of the semantic control system using resting-state functional
      magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean
      mini-mental state examination = 20.5) and in a group of age-matched healthy
      controls (n = 19). Voxel-wise analysis spatially constrained in the left fronto
      temporal semantic control network identified two regions with altered functional
      connectivity (FC) in AD patients, specifically in the pars opercularis (POp,
      BA44) and in the posterior middle temporal gyrus (pMTG, BA21). Using whole-brain
      seed-based analysis, we demonstrated that these two regions have altered FC even
      beyond the semantic control network. In particular, the pMTG displayed a wide
      distributed pattern of lower connectivity to several brain regions involved in
      language-semantic processing, along with a possibly compensatory higher
      connectivity to the Wernicke's area. We conclude that in mild AD brain regions
      belonging to the semantic control network are abnormally connected not only
      within the network, but also to other areas known to be critical for language
      processing.

PMID- 29197561
TI  - Phase angle is related with inflammatory and oxidative stress biomarkers in older
      women.
AB  - BACKGROUND: The aim of this study was to examine the relation between phase angle
      (PhA) and inflammatory and oxidative stress biomarkers in older women. METHODS:
      One hundred and fifty-five physically independent older women participated in
      this study (67.7+/-5.7years, 27.0+/-4.4kg/m2). Inflammatory markers included
      interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and acute phase
      reactive protein (CRP). Oxidative stress biomarkers comprised superoxide
      dismutase (SOD), catalase (CAT), advanced oxidation protein products (AOPP), and
      total radical-trapping antioxidant potential (TRAP). A spectral bioelectrical
      impedance device was used to estimate resistance (R) and reactance (Xc) at
      frequency 50kHz, and subsequently PhA was calculated as arc-tangent (Xc/R)*180
      degrees /pi. The covariates appendicular lean soft-tissue (ALST), trunk fat mass,
      and total body fat were determined by whole-body dual-energy X-ray
      absorptiometry. Linear regression analysis was conducted to further test if PhA
      is related with the dependent variables, after adjusting for potential
      covariates. RESULTS: After controlling for the potential covariates (age, trunk
      fat mass, ALST, and number of diseases) PhA exhibited a significant inverse
      relation with IL-6 (beta=-0.97; P<0.01), TNF-alpha (beta=-0.84; P<0.01), and CRP
      (beta=-0.58; P<0.01). Conversely, PhA was significantly related to CAT
      (beta=7.27; P<0.01), SOD (beta=10.55; P<0.01) and TRAP (beta=73.08; P<0.01). The
      AOPP did not demonstrate a significant correlation with PhA (P>0.05). CONCLUSION:
      Our findings show that PhA is a simple and relevant explanatory variable which is
      related inflammatory and stress oxidative markers in physically independent older
      women, regardless of age, number of diseases, and body composition.

PMID- 29197562
TI  - Various cellular stress components change as the rat ages: An insight into the
      putative overall age-related cellular stress network.
AB  - Cellular stress is mainly comprised of oxidative, nitrosative, and endoplasmic
      reticulum stresses and has long been correlated to the ageing process.
      Surprisingly, the age-related difference among the various components in each
      independent stress pathway and the possible significance of these components in
      relation to the overall cellular stress network remain to be clearly elucidated.
      In this study, we obtained blood from ageing rats upon reaching 20-, 40-, and 72
      wk.-old. Subsequently, we measured representative cellular stress-linked
      biomolecules (H2O2, glutathione reductase, heme, NADPH, NADP, nitric oxide,
      GADD153) and cell signals [substance P (SP), free fatty acid, calcium, NF-kappaB]
      in either or both blood serum and cytosol. Subsequently, network analysis of the
      overall cellular stress network was performed. Our results show that there are
      changes affecting stress-linked biomolecules and cell signals as the rat ages.
      Additionally, based on our network analysis data, we postulate that NADPH, H2O2,
      GADD153, and SP are the key components and the interactions between these
      components are central to the overall age-related cellular stress network in the
      rat blood. Thus, we propose that the main pathway affecting the overall age
      related cellular stress network in the rat blood would entail NADPH-related
      oxidative stress (involving H2O2) triggering GADD153 activation leading to SP
      induction which in-turn affects other cell signals.

PMID- 29197564
TI  - Impact breakage of pharmaceutical tablets.
AB  - Tablets are the most common solid dosage form of pharmaceutical active
      ingredients due to their ease of use. Their dissolution behaviour depends on the
      particle size distribution and physicochemical properties of the formulation, and
      the compression process, which need to be optimised for producing consistently
      robust tablets, as weaker tablets are often prone to breakage during production,
      transport and end use. Tablet strength is typically determined by diametric
      compression and friability tests. The former gives rise to propagation of a crack
      on a plane along the compression axis, whilst the latter, carried out in a
      rotating drum, incurs surface damage and produces chips and debris. These tests
      produce different measures of strength, neither of which have been correlated
      with mechanical properties that are accountable for breakage, i.e. hardness,
      elastic modulus and fracture toughness. We propose a new method based on single
      tablet impact testing, following the work of Ghadiri and Zhang, 2002, who
      analysed particle damage by propagation of sub-surface lateral cracks and
      identified the fundamental form accountable for impact surface damage to be a
      lumped parameter related to hardness and fracture toughness. Microindentation,
      carried out separately, to determine fracture toughness led to complete failure
      of the tablets, hence an unreliable measurement of fracture toughness and no
      correlation with the experimental trend. In addition, by assuming the fracture
      toughness to be proportional to the square root of Young's modulus, the
      indentation measurements do not correlate well with the impact breakage. The
      discrepancy between the impact and indentation methods is expected to be due to
      mechanical property variation across the tablet surface, and with strain rate.
      The impact method is a more suitable test to describe tablet propensity for
      attrition as it directly represents the failure mode tablets may experience
      during processing under well-defined conditions. In contrast, the friability test
      subjects tablets to a similar breakage mechanism but under less well-defined
      conditions, whilst the compression test represents a different failure mode that
      is not representative of stresses incurred during processing.

PMID- 29197563
TI  - GABAergic interneurons: The orchestra or the conductor in fear learning and
      memory?
AB  - Fear conditioning is a form of associative learning that is fundamental to
      survival and involves potentiation of activity in excitatory projection neurons
      (PNs). Current models stipulate that the mechanisms underlying this process
      involve plasticity of PN synapses, which exhibit strengthening in response to
      fear conditioning. However, excitatory PNs are extensively modulated by a diverse
      array of GABAergic interneurons whose contributions to acquisition, storage, and
      expression of fear memory remain poorly understood. Here we review emerging
      evidence that genetically-defined interneurons play important subtype-specific
      roles in processing of fear-related stimuli and that these dynamics shape PN
      firing through both inhibition and disinhibition. Furthermore, interneurons
      exhibit structural, molecular, and electrophysiological evidence of fear learning
      induced synaptic plasticity. These studies warrant discarding the notion of
      interneurons as passive bystanders in long-term memory.

PMID- 29197565
TI  - Molecular and biochemical biomarkers for diagnosis and therapy monitorization of
      Niemann-Pick type C patients.
AB  - BACKGROUND: Niemann-Pick type C (NP-C), one of 50 inherited lysosomal storage
      disorders, is caused by NPC protein impairment that leads to unesterified
      cholesterol accumulation in late endosomal/lysosomal compartments. The clinical
      manifestations of NP-C include hepatosplenomegaly, neurological and psychiatric
      symptoms. Current diagnosis for NP-C is based on observation of the accumulated
      cholesterol in fibroblasts of affected individuals, using an invasive and time
      expensive test, called Filipin staining. Lately, two metabolites that are
      markedly increased in NP-C patients are arising as biomarkers for this disease
      screening: 7-ketocholesterol and cholestane-3beta,5alpha,6beta-triol, both
      oxidized cholesterol products. OBJECTIVE: In this work, we aimed to evaluate the
      performance of cholestane-3beta,5alpha,6beta-triol analysis for the screening and
      monitoring of NPC patients, correlating it with chitotriosidase levels, Filipin
      staining and molecular analysis. It was investigated 76 non-treated individuals
      with NP-C suspicion and also 7 patients with previous NP-C diagnosis under
      treatment with miglustat, in order to verify the cholestane-3beta,5alpha,6beta
      triol value as a tool for therapy monitoring. RESULTS: Considering molecular
      assay as golden standard, it was verified that cholestane-3beta,5alpha,6beta
      triol analysis presented 88% of sensitivity, 96.08% of specificity, a positive
      and negative predictive value calculated in 91.67% and 94.23%, respectively, for
      the diagnosis of NP-C. Chitotriosidase levels were increased in patients with
      positive molecular analysis for NP-C. For Filipin staining, it was found 1 false
      positive, 7 false negative and 24 inconclusive cases, showing that this assay has
      important limitations for NP-C diagnosis. Besides, we found a significant
      decrease in cholestane-3beta,5alpha,6beta-triol concentrations in NP-C patients
      under therapy with miglustat when compared to non-treated patients. CONCLUSION:
      Taken together, the present data show that cholestane-3beta,5alpha,6beta-triol
      analysis has a high potential to be an important NP-C screening assay, and also
      can be used for therapy monitorization with miglustat in NP-C patients.

PMID- 29197566
TI  - Local subcutaneous injection of chlorogenic acid inhibits the nociceptive
      trigeminal spinal nucleus caudalis neurons in rats.
AB  - Acute administration of chlorogenic acid (CGA) in vitro was recently shown to
      modulate potassium channel conductance and acid-sensing ion channels (ASICs) in
      the primary sensory neurons; however, in vivo peripheral effects of CGA on the
      nociceptive mechanical stimulation of trigeminal neuronal activity remains to be
      determined. The present study investigated whether local administration of CGA in
      vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal
      nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit
      recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited
      by non-noxious and noxious orofacial mechanical stimulation in pentobarbital
      anesthetized rats. The mean number of SpVc WDR neuronal firings responding to
      both non-noxious and noxious mechanical stimuli were significantly and dose
      dependently inhibited by local subcutaneous administration of CGA (0.1-10mM),
      with the maximal inhibition of discharge frequency revealed within 10min and
      reversed after approximately 30min. The mean frequency of SpVc neuronal discharge
      inhibition by CGA was comparable to that by a local anesthetic, the sodium
      channel blocker, 1% lidocaine. These results suggest that local CGA injection
      into the peripheral receptive field suppresses the excitability of SpVc neurons,
      possibly via the activation of voltage-gated potassium channels and modulation of
      ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons.
      Therefore, local injection of CGA could contribute to local anesthetic agents for
      the treatment of trigeminal nociceptive pain.

PMID- 29197567
TI  - Biologically anchored chitosan/gelatin-SrHAP scaffold fabricated on Titanium
      against chronic osteomyelitis infection.
AB  - The obstacles faced to treat chronic osteomyelitis infection clinically led to
      the search for an ideal biomaterial, resulted in combining two major aspects of
      bone tissue engineering namely surface modified metallic implant and polymer
      nanocomposite scaffold. In the present study Gelatin - Strontium incorporated
      Hydroxyapatite (SrHAP) forming HG scaffold, vancomycin loaded chitosan -gelatin
      polyelectrolyte complex incorporated gelatin-SrHAP, forming HV scaffolds (HV1
      0.5wt% and HV2-1wt% vancomycin) were investigated. The HG, HV1 and HV2 scaffolds
      were successfully fabricated on Cp-Ti through anchoring by treatment with
      dopamine, which forms a bidentate co-ordination through NH bonding.
      Interconnected porous morphology of the scaffolds was confirmed, besides the
      globular Sr-HAP found in HV2 scaffold. The total amount of vancomycin
      encapsulation for HV1 and HV2 scaffolds were determined to be 47.55+/-1.6MUg and
      82.45+/-3.5MUg respectively. Among the scaffolds studied HV2 scaffold were found
      to have a significant antibacterial activity for both MRSA and MSSA strains
      compared to Cp-Ti, HG and HV1 scaffolds. The HV2 scaffold also had significantly
      higher% of cell viability compared to Cp-Ti, HG and HV1 scaffolds. Furthermore,
      the presence of the drug vancomycin had no toxic effect on the cells, rather it
      aided in enhanced cell proliferation and spreading.

PMID- 29197568
TI  - Inhibition of insulin amyloid fibrillation by Morin hydrate.
AB  - We report here the inhibition of amyloid fibrillation of human insulin in vitro
      by Morin hydrate, a naturally occurring small molecule. Using spectroscopic
      assays and transmission electron microscopy, we found that Morin hydrate
      effectively inhibits insulin amyloid fibrillation in a dose dependent manner with
      more than 80% inhibition occurring even at only a 1:1 concentration. As suggested
      by fluorescence spectroscopic titration studies, Morin hydrate binds to insulin
      with a fairly strong affinity of -26.436kJmol-1. Circular dichroism (CD)
      spectroscopy was used to analyse structural changes of insulin in the presence of
      Morin hydrate demonstrating the ability of Morin hydrate to bind with the native
      monomeric protein and/or its near native state, intermediate oligomeric species
      and amyloid fibrils. Based on computational docking and molecular dynamics study,
      we propose that Morin hydrate binds to residues having greater aggregation
      propensity and prevent structural and/or conformational changes leading to
      amyloid fibrillation. Morin hydrate should also bind to fibrils by hydrogen
      bonding and/or hydrophobic forces throughout the surface, stabilize them and
      inhibit the release of oligomeric species which could be nuclei or template for
      further fibrillation. Overall results provide an insight into the mechanism of
      inhibition of insulin amyloid fibrillation by Morin hydrate.

PMID- 29197569
TI  - Non-covalent interaction between CA-TAT and calf thymus DNA: Deciphering the
      binding mode by in vitro studies.
AB  - CA-TAT, a novel peptide analog, was modified at the N-terminus of TAT (47-57),
      the cell-penetrating peptide transacting activator of transcription, by attaching
      cecropin A (1-7). CA-TAT, TAT (47-57), and cecropin A (1-7) were synthesized
      using standard Fmoc solid-phase peptide synthesis procedures, purified using
      reversed-phase high performance liquid chromatography (RP-HPLC), and
      characterized using ESI-MS. CA-TAT demonstrated antibacterial activities against
      bacteria with low hemolysis (MHC > 128 MUM). The minimum inhibitory concentration
      (MIC) values of CA-TAT were in the range of 1-16 MUM, which completely inhibited
      both gram-positive and gram-negative bacteria. The interactions between CA-TAT or
      TAT (47-57) and calf thymus DNA (ct-DNA) were investigated using multi
      spectroscopic techniques and viscometry. The results showed that both CA-TAT and
      TAT (47-57) can interact with DNA via the minor groove-binding mode, and binding
      constant was calculated to be 2.83 * 105 L mol-1 at 310 K, which is lower than
      that with the classical intercalation binder ethidium bromide (EB). Compared with
      TAT (47-57) or cecropin A (1-7), CA-TAT combined with DNA much closer. The study
      results suggest that CA-TAT can be used as a novel antibacterial peptide in the
      development of new antibiotics because of its antibacterial activity that targets
      intracellular DNA.

PMID- 29197570
TI  - Polymer coated mesoporous ceramic for drug delivery in bone tissue engineering.
AB  - Treatment strategy for various bone fracture and defects the researchers are
      focusing to develop a new carrier for delivering the drug into injured area with
      controlled and sustained manner using biomaterials with dynamic architecture
      orientation. Ceramic materials are resembled with bone compositional architecture
      and better bioactivity, degradability as well as antimicrobial activity made its
      enormous application in bone tissue engineering (BTE). Current focus in
      regenerative medicine were orchestration of biomaterials with the capacity of
      loading the drugs, growth factors, ionic components to promote better healing of
      bone tissue. Mesoporous type materials owed a great look towards the delivery of
      drugs, growth factors, etc in BTE because of its unique geometry. So the guest
      molecules loaded with geometrically organized ceramics would deliver onto the
      site of injury in controlled manner also the guiding and regulation of delivery
      of molecules have been controlled with the polymers response to different
      stimulation or biochemical factors as either scaffold or encapsulated particles
      for bone regeneration. Hence the review aims to describing the recent progress in
      bone tissue engineering using the ceramic based mesoporous materials encapsulated
      with polymers respond to different physiochemical stimulation for the efficient
      and controlled delivery of drug/growth factors for better bone healing.

PMID- 29197571
TI  - Chitin from Agaricus bisporus: Extraction and characterization.
AB  - Chitin was isolated from three main fruit body parts of the Agaricus bisporus
      mushroom, i.e. pileus, stipes and gills. Chitin was extracted by alkaline
      treatment of A. bisporus fruit body parts in 1 M NaOH at 80  degrees C for 2
      h.The lyophilized fruit bodies were examined by SEM and exhibited a porous
      structure that is favorable to polysaccharide extraction. A mild extraction
      method was adopted to limit the degradation of chitin. The highest extraction
      yield of chitin was obtained for stipes (7.4% of dry weight). For pileus and
      gills, yields of chitin were 6.4% and 5.9%, respectively. Chitin extracted from
      stipes was characterized by thermal analysis, X-ray diffraction, infrared
      spectroscopy and solid-state 13C NMR. Results showed that the extracted chitin
      was in the alpha form, with a 63% crystalline index (CrI) and a degree of N
      acetylation (DA) of 70%. The presence of proteins and glucans were not observed
      in the extracted chitin.

PMID- 29197572
TI  - Diversity in cadmium accumulation and resistance associated with various
      metallothionein genes (type III) in Phytolacca americana L.
AB  - Metallothioneins (MTs) are known for their heavy metal deoxidation during
      phytoremediation. To estimate their roles in the cadmium (Cd) hyperaccumulator
      Phytolacca americana L., three MT genes, PaMT3-1, PaMT3-2 and PaMT3-3, belonging
      to the MT3 subfamily were cloned. They separately encoded 63, 65 and 65 amino
      acids, containing12, 10 and 11 cysteines (Cys), respectively. Each gene was
      individually transformed and expressed in Escherichia coli cells. A Cd-resistance
      assay showed that the recombinant strains had enhanced survival rates, especially
      those containing PaMT3-1 and PaMT3-3. Additionally, the recombinant strains were
      high Cd accumulators, with the recombinant PaMT3-1's maximum accumulation being
      2.16 times that of the empty vector strains. The numbers of cysteines and the
      structures of MT proteins were associated with the Cd enrichment and resistance
      capabilities. PaMT3-1 could be an effective gene resource in future plant Cd
      remediation-related breeding programs.

PMID- 29197573
TI  - Development of the emotional brain.
AB  - In this article, we highlight the importance of dynamic reorganization of neural
      circuitry during adolescence, as it relates to the development of emotion
      reactivity and regulation. We offer a neurobiological account of hierarchical,
      circuit-based changes that coincide with emotional development during this time.
      Recent imaging studies suggest that the development of the emotional brain
      involves a cascade of changes in limbic and cognitive control circuitry. These
      changes are particularly pronounced during adolescence, when the demand for self
      regulation across a variety of emotional and social situations may be greatest.
      We propose that hierarchical changes in circuitry, from subcortico-subcortical to
      subcortico-cortical to cortico-subcortical and finally to cortico-cortical, may
      underlie the gradual changes in emotion reactivity and regulation throughout
      adolescence into young adulthood, with changes at each level being necessary for
      the instantiation of changes at the next level.

PMID- 29197574
TI  - Endothelial microparticles-mediated transfer of microRNA-19b promotes
      atherosclerosis via activating perivascular adipose tissue inflammation in apoE-/
      mice.
AB  - Microparticles(MPs) are the major carriers of circulating microRNAs. Our previous
      study has shown that microRNA (miR)-19b in endothelial cell-derived
      microparticles (EMPs) is significantly increased in patients with unstable
      angina. However, little is known about the relationship between miR-19b in EMPs
      and the progression of atherosclerosis. The aim of the present study was to
      define the role and potential mechanism of miR-19b incorporated in EMPs in the
      development of atherosclerosis. Western-diet-fed apoE-/- mice were injected with
      phosphate buffered solution(PBS), EMP carrying microRNA control(EMPcontrol) or
      miR-19b mimic (EMPmiR19b) intravenously. Systemic treatment with EMPmiR19b
      significantly accelerated carotid artery atherosclerosis progression by
      increasing lipid, macrophages and smooth muscle cells and decreasing collagen
      content in atherosclerotic plaque. Fluorescence-labelled EMPmiR19b injection
      proved that miR-19b could be transported into perivascular adipose tissue(PVAT)
      by EMPs. EMPmiR19b treatment also promoted inflammatory cytokines secretion and
      macrophages infiltration in PVAT. In further experiment, apoE-/- mice were
      divided into 3 groups: EMPcontrolPVAT(+), EMPmiR19bPVAT(+) and EMPmiR19bPVAT(-),
      based on removing or keeping pericarotid adipose tissue and injected with
      EMPcontrol or EMPmiR19b. Loss of PVAT attenuated EMPmiR19b-mediated effects on
      increasing carotid atherosclerosis formation and inflammatory cytokines level in
      plaque. EMPmiR19b inhibited suppressor of cytokine signaling 3 (SOCS3) expression
      in PVAT. Our findings demonstrate that miR-19b in EMPs exaggerates
      atherosclerosis progression by augmenting PVAT-specific inflammation proceeded by
      downregulating SOCS3 expression.

PMID- 29197575
TI  - Trametinib suppresses HIV-1 replication by interfering with the disassembly of
      human immunodeficiency virus type 1 capsid core.
AB  - Our previous study showed that the phosphorylation of a highly conserved serine
      residue, Ser16 in the human immunodeficiency virus type 1 (HIV-1) capsid (CA)
      protein is promoted by virion-incorporated extracellular signal-regulated kinase
      2 (ERK2) and required for proper peptidyl-prolyl isomerase (Pin1)-mediated
      uncoating. Interestingly, western blot analysis demonstrated that
      phosphorylated/activated mitogen-activated protein kinase kinase 1/2 (MEK1/2),
      the upstream activator of ERK2, as well as ERK2 are incorporated into virions.
      Here, we show that the MEK1/2 selective allosteric inhibitor Trametinib reduces
      HIV-1 infectivity via the decrease in virion-incorporated ERK2 phosphorylation.
      The treatment of chronic HIV-1-infected T-cell line, CEM/LAV-1 cells with
      Trametinib results in a decrease in ERK2 phosphorylation in the virions. The
      viruses have relatively low infectivity and impaired reverse transcription. Cell
      based fate-of-capsid uncoating assay showed that the reduction in infectivity was
      caused by a functional impairment of the uncoating process. Furthermore, the
      viruses from Trametinib-treated CEM/LAV-1 cells also showed decreased reverse
      transcription efficiency and attenuated multiple rounds of replication in human
      peripheral blood mononuclear cells (PBMCs). Taken together, these findings
      suggest that Trametinib suppresses HIV-1 replication by abrogating the proper
      disassembly of CA core.

PMID- 29197576
TI  - Neferine, is not inducer but blocker for macroautophagic flux targeting on
      lysosome malfunction.
AB  - Neferine, an alkaloid isolated from Lotus seeds, displays multiple
      pharmacological effects that counter cancer, oxidants, and arrhythmia. It was
      initially identified as a strong inducer for macroautophagy in cancer cells by
      suppressing AMPK/mTOR signaling. In this study, we found that autophagy signaling
      was inhibited in the condition of neferine treatment. Exposure to neferine
      resulted in the accumulation of LC3-II and an associated adaptor protein,
      p62/SQSTM1. Knockdown of ATG5 failed to reduce the accumulation of LC3-II induced
      by neferine. The electron microscopy (EM) images showed that neferine induce
      accumulation of multi-vesicle bodies (MVB) and failure of lysosome maturation.
      Moreover, exposure to neferine reduced maturation of cathepsin D and impaired the
      degradation of autophagic and phagocytic cargos. Rather than stimulate autophagic
      flux, the data indicate that neferine impaired lysosomes to block degradation
      within phagolysosomes.

PMID- 29197577
TI  - Solution structure analysis of the periplasmic region of bacterial flagellar
      motor stators by small angle X-ray scattering.
AB  - The bacterial flagellar motor drives the rotation of helical flagellar filaments
      to propel bacteria through viscous media. It consists of a dynamic population of
      mechanosensitive stators that are embedded in the inner membrane and activate in
      response to external load. This entails assembly around the rotor, anchoring to
      the peptidoglycan layer to counteract torque from the rotor and opening of a
      cation channel to facilitate an influx of cations, which is converted into
      mechanical rotation. Stator complexes are comprised of four copies of an integral
      membrane A subunit and two copies of a B subunit. Each B subunit includes a C
      terminal OmpA-like peptidoglycan-binding (PGB) domain. This is thought to be
      linked to a single N-terminal transmembrane helix by a long unstructured peptide,
      which allows the PGB domain to bind to the peptidoglycan layer during stator
      anchoring. The high-resolution crystal structures of flagellar motor PGB domains
      from Salmonella enterica (MotBC2) and Vibrio alginolyticus (PomBC5) have
      previously been elucidated. Here, we use small-angle X-ray scattering (SAXS). We
      show that unlike MotBC2, the dimeric conformation of the PomBC5 in solution
      differs to its crystal structure, and explore the functional relevance by
      characterising gain-of-function mutants as well as wild-type constructs of
      various lengths. These provide new insight into the conformational diversity of
      flagellar motor PGB domains and experimental verification of their overall
      topology.

PMID- 29197578
TI  - Magnesium-based bioceramics in orthopedic applications.
AB  - : Magnesium ions are directly involved in numerous biological mechanisms; for
      example, they play an important part in the regulation of ion channels, DNA
      stabilization, enzyme activation and stimulation of cell growth and
      proliferation. This alkaline earth metal has gained great popularity in
      orthopedic applications in recent years. Magnesium-based bioceramics include a
      large group of magnesium containing compounds such as oxides, phosphates and
      silicates, that are involved in orthopedic applications like bone cements, bone
      scaffolds or implant coatings. This article aims to give a comprehensive review
      on different magnesium-based bioceramics, e.g. magnesium phosphates (MgO-P2O5),
      calcium magnesium phosphates (CaO-MgO-P2O5), and magnesium glasses (SiO2-MgO)
      with a strong focus on the chemistry and properties of magnesium phosphate
      containing cements as the main application form. In addition, the processing of
      magnesium phosphate minerals into macroporous scaffolds for tissue engineering
      applications by either using traditional porogens or by additive manufacturing
      approaches are reflected. Finally, the biological in vitro and in vivo properties
      of magnesium phosphates for bone regeneration are summarized, which show
      promising results regarding the application as bone replacement material, but
      still lack in terms of testing in large animal models, load-bearing application
      sites and clinical data. STATEMENT OF SIGNIFICANCE: Though bone substitutes from
      calcium phosphates have been investigated for a long time, a new trend is visible
      in the biomaterials sector: magnesium based bioceramics from magnesium phosphates
      and silicates due to the special biological significance of magnesium ions in
      enzymatic activation, cell growth and proliferation, etc. In contrast to pure
      magnesium implants, such formulations do not release hydrogen during degradation.
      As with calcium based bioceramics, magnesium based bioceramics are used for the
      development of diverse applications such as cements, macroporous scaffolds and
      coatings. From this perspective, we present a systematic overview on diverse
      kinds of magnesium based bioceramics, their processing regimes for different
      clinical purposes and their behavior both in vitro and in vivo.

PMID- 29197579
TI  - Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked
      collagen used as an injectable bulking agent for urinary incontinence treatment.
AB  - : Endoscopic injection of bulking agents has been widely used to treat urinary
      incontinence, often due to urethral sphincter complex insufficiency. The aim of
      the study was to develop a novel injectable bioactive collagen-fibrin bulking
      agent restoring long-term continence by functional muscle tissue regeneration.
      Fibrin micro-beads were engineered using a droplet microfluidic system. They had
      an average diameter of 140 MUm and recombinant fibrin-binding insulin-like growth
      factor-1 (alpha2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A
      plasmin fibrin degradation assay showed that 72.5% of the initial amount of
      alpha2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin
      micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced
      cell attachment and the migration of human urinary tract smooth muscle cells,
      however, no change of the cellular metabolic activity was seen. These bioactive
      micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a
      carrier. The collagen concentration, the degree of crosslinking, and the
      mechanical behavior of this bioactive collagen-fibrin injectable were comparable
      to reference samples. This novel injectable showed no burst release of the growth
      factor, had a positive effect on cell behavior and may therefore induce smooth
      muscle regeneration in vivo, necessary for the functional treatment of stress and
      other urinary incontinences. STATEMENT OF SIGNIFICANCE: Urinary incontinence is
      involuntary urine leakage, resulting from a deficient function of the sphincter
      muscle complex. Yet there is no functional cure for this devastating condition
      using current treatment options. Applied physical and surgical therapies have
      limited success. In this study, a novel bioactive injectable bulking agent,
      triggering new muscle regeneration at the injection site, has been evaluated.
      This injectable consists of cross-linked collagen and fibrin micro-beads,
      functionalized with bound insulin-like growth factor-1 (alpha2PI1-8-MMP-IGF-1).
      These bioactive fibrin micro-beads induced human smooth muscle cell migration in
      vitro. Thus, this injectable bulking agent is apt to be a good candidate for
      regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for
      urinary incontinence.

PMID- 29197580
TI  - Evaluation of reproductive toxicity in rats treated with triclosan.
AB  - Triclosan (TCS) is an antibacterial agent used in a variety of consumer products
      such as: soaps, deodorant, and toothpaste, among others. Some studies have
      reported the (anti)androgenic effects of TCS in the male reproductive system,
      raising concerns about its effects on the reproductive axis. In this study, the
      (anti)androgenicity of TCS was evaluated in the Hershberger assay in 52-day old
      male Wistar rats. Additionally, the sexual behavior, sperm motility, sperm
      viability, and testicular histomorphometry were evaluated in a second protocol to
      investigate the reproductive effects of TCS in 49-day old male Wistar rats. The
      dosages were administered based on the acceptable daily intake for TCS, in
      addition to 3 and 10-fold higher doses. Our results demonstrated that TCS, in the
      doses administered, did not act as an endocrine disrupter (ED), with no
      (anti)androgenic effect in the Hershberger assay and without interfering with the
      parameters evaluated in the reproductive toxicity study.

PMID- 29197581
TI  - Proteomic analysis of Bombyx mori molting fluid: Insights into the molting
      process.
AB  - : Molting is an essential biological process occurring multiple times throughout
      the life cycle of most Ecdysozoa. Molting fluids accumulate and function in the
      exuvial space during the molting process. In this study, we used liquid
      chromatography-tandem mass spectrometry to investigate the molting fluids to
      analyze the molecular mechanisms of molting in the silkworm, Bombyx mori. In
      total, 375 proteins were identified in molting fluids from the silkworm at 14-16h
      before pupation and eclosion, including 12 chitin metabolism-related enzymes, 35
      serine proteases, 15 peptidases, and 38 protease inhibitors. Gene ontology
      analysis indicated that "catalytic" constitutes the most enriched function in the
      molting fluid. Gene expression patterns and bioinformatic analyses suggested that
      numerous enzymes are involved in the degradation of cuticle proteins and chitin.
      Protein-protein interaction network and activity analyses showed that protease
      inhibitors are involved in the regulation of multiple pathways in molting fluid.
      Additionally, many immune-related proteins may be involved in the immune defense
      during molting. These results provide a comprehensive proteomic insight into
      proteolytic enzymes and protease inhibitors in molting fluid, and will likely
      improve the current understanding of physiological processes in insect molting.
      BIOLOGICAL SIGNIFICANCE: Insect molting constitutes a dynamic physiological
      process. To better understand this process, we used LC-MS/MS to investigate the
      proteome of silkworm molting fluids and identified key proteins involved in
      silkworm molting. The biological processes of the old cuticle degradation pathway
      and immune defense response were analyzed in the proteome of silkworm molting
      fluid. We report that protease inhibitors serve as key factors in the regulation
      of the molting process. The proteomic results provide new insight into biological
      molting processes in insects.

PMID- 29197582
TI  - Label-free quantitative proteomic profiling of colon cancer cells identifies
      acetyl-CoA carboxylase alpha as antitumor target of Citrus limon-derived
      nanovesicles.
AB  - : We have previously isolated exosome-like nanoparticles from Citrus-limon juice,
      able to inhibit in vitro and in vivo tumor cell growth. In order to deeply
      understand the mechanism underlying nanovesicle effects, we performed a proteomic
      profile of treated colorectal cancer cells. Among the proteins differentially
      expressed after nanovesicle treatment, we found a significant downregulation of
      the Acetyl-CoA Carboxylase 1 (ACACA) and we demonstrated that silencing ACACA in
      cancer cells leads to a reduction of cell growth. Our study proved that the anti
      tumor effects of Citrus-limon nanovesicles is partly mediated by lipid metabolism
      inhibition, in particular via ACACA downregulation. SIGNIFICANCE: This study
      represents the attempt to achieve, by a proteomic approach, a better
      understanding of the role of lemon nanovesicles in affecting colorectal cancer
      cell growth.

PMID- 29197583
TI  - Evaluation of ion mobility for the separation of glycoconjugate isomers due to
      different types of sialic acid linkage, at the intact glycoprotein, glycopeptide
      and glycan level.
AB  - : The study of protein glycosylation can be regarded as an intricate but very
      important task, making glycomics one of the most challenging and interesting,
      albeit under-researched, type of "omics" science. Complexity escalates remarkably
      when considering that carbohydrates can form severely branched structures with
      many different constituents, which often leads to the formation of multiple
      isomers. In this regard, ion mobility (IM) spectrometry has recently demonstrated
      its power for the separation of isomeric compounds. In the present work, the
      potential of traveling wave IM (TWIMS) for the separation of isomeric
      glycoconjugates was evaluated, using mouse transferrin (mTf) as model
      glycoprotein. Particularly, we aim to assess the performance of this platform for
      the separation of isomeric glycoconjugates due to the type of sialic acid
      linkage, at the intact glycoprotein, glycopeptide and glycan level.
      Straightforward separation of isomers was achieved with the analysis of released
      glycans, as opposed to the glycopeptides which showed a more complex pattern.
      Finally, the developed methodology was applied to serum samples of mice, to
      investigate its robustness when analyzing real complex samples. BIOLOGICAL
      SIGNIFICANCE: Ion mobility mass spectrometry is a promising analytical technique
      for the separation of glycoconjugate isomers due to type of sialic acid linkage.
      The impact of such a small modification in the glycan structure is more evident
      in smaller analytes, reason why the analysis of free glycans was easier compared
      to the intact protein or the glycopeptides. The established methodology could be
      regarded as starting point in the separation of highly decorated glycoconjugates.
      This is an important topic nowadays, as differences in the abundance of some
      glycan isomers could be the key for the early diagnosis, control or
      differentiation of certain diseases, such as inflammation or cancer.

PMID- 29197585
TI  - Studying assembly of the BAM complex in native membranes by cellular solid-state
      NMR spectroscopy.
AB  - Significant progress has been made in obtaining structural insight into the
      assembly of the beta-barrel assembly machinery complex (BAM). These
      crystallography and electron microscopy studies used detergent as a membrane
      mimetic and revealed structural variations in the central domain, BamA, as well
      as in the lipoprotein BamC. We have used cellular solid-state NMR spectroscopy to
      examine the entire BamABCDE complex in native outer membranes and obtained data
      on the BamCDE subcomplex in outer membranes, in addition to synthetic bilayers.
      To reduce spectral crowding, we utilized proton-detected experiments and employed
      amino-acid specific isotope-labelling in (13C, 13C) correlation experiments.
      Taken together, the results provide insight into the overall fold and assembly of
      the BAM complex in native membranes, in particular regarding the structural
      flexibility of BamC in the absence of the core unit BamA.

PMID- 29197584
TI  - Depletion of transglutaminase 2 in neurons alters expression of extracellular
      matrix and signal transduction genes and compromises cell viability.
AB  - The protein transglutaminase 2 (TG2) has been implicated as a modulator of
      neuronal viability. TG2's role in mediating cell survival processes has been
      suggested to involve its ability to alter transcriptional events. The goal of
      this study was to examine the role of TG2 in neuronal survival and to begin to
      delineate the pathways it regulates. We show that depletion of TG2 significantly
      compromises the viability of neurons in the absence of any stressors. RNA
      sequencing revealed that depletion of TG2 dysregulated the expression of 86 genes
      with 59 of these being upregulated. The genes that were upregulated by TG2
      knockdown were primarily involved in extracellular matrix function, cell
      signaling and cytoskeleton integrity pathways. Finally, depletion of TG2
      significantly reduced neurite length. These findings suggest for the first time
      that TG2 plays a crucial role in mediating neuronal survival through its
      regulation of genes involved in neurite length and maintenance.

PMID- 29197586
TI  - pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory
      properties against cisplatin-induced hearing loss.
AB  - Polymeric nanoparticles (NPs) based on smart synthetic amphiphilic copolymers are
      used to transport and controlled release dexamethasone in the inner ear to
      protect against the ototoxic effect of cisplatin. The NPs were based on a mixture
      of two pseudo-block polymer drugs obtained by free radical polymerization:
      poly(VI-co-HEI) and poly(VP-co-MVE) or poly(VP-co-MTOS), being VI 1
      vinylimidazole, VP N-vinylpyrrolidone, and HEI, MVE and MTOS the methacrylic
      derivatives of ibuprofen, alpha-tocopherol and alpha-tocopheryl succinate,
      respectively. The NPs were obtained by nanoprecipitation with appropriate
      hydrodynamic properties, and isoelectric points that matched the pH of inflamed
      tissue. The NPs were tested both in vitro (using HEI-OC1 cells) and in vivo
      (using a murine model) with good results. Although the concentration of
      dexamethasone administered in the NPs is around two orders of magnitude lower
      that the conventional treatment for intratympanic administration, the NPs
      protected from the cytotoxic effect of cisplatin when the combination of the
      appropriate properties in terms of size, zeta potential, encapsulation efficiency
      and isoelectric point were achieved. To the best of our knowledge this is the
      first time that pH sensitive NPs are used to protect from cisplatin-induced
      hearing loss by intratympanic administration.

PMID- 29197588
TI  - Genome-wide profiling of gene expression and DNA methylation provides insight
      into low-altitude acclimation in Tibetan pigs.
AB  - Efforts have been made to characterize the high-altitude adaption in Tibetan pigs
      and identified vast of genes or genomic regions undergone natural selection.
      Nonetheless, information concerning gene expression and DNA methylation changes
      response to low-altitude acclimation in Tibetan pigs is long overdue. To explore
      the exceptional mechanisms of gene expression and DNA methylation that are
      induced by low altitude environments in Tibetan pigs, we performed a comparative
      transcriptomic and DNA methylation analysis of skeletal muscle between indigenous
      Tibetan pigs that reside in high altitude regions (~4000m) and their counterparts
      that migrated to the geographically neighboring low-altitude regions (~500m) for
      nearly ten generations. Many genes that related to hypoxia response (EGLN3 and
      FLT1) and energy metabolism (TFB2M) were differentially expressed, but without
      significant DNA methylation changes. We also found genes embedded in
      differentially methylated regions were mainly involved in 'Starch and sucrose
      metabolism', 'glucuronosyltransferase activity' processes. Specifically, our
      results showed increased SIN3A mRNA expression, with hypomethylation status of
      its promoter, in longissimus dorsi muscle of low-altitude Tibetan pig. Another
      gene, CACNG6, showed decreasing expression level with an elevated methylation in
      its intron 3. These results indicated DNA-methylation-mediated expression
      alterations in low-altitude acclimation. We envision that this study will serve
      as a valuable resource for mammal acclimation research and agricultural food
      industry.

PMID- 29197587
TI  - Analysis of miRNA expression profiles in melatonin-exposed GC-1 spg cell line.
AB  - Melatonin is an endocrine neurohormone secreted by pinealocytes in the pineal
      gland. It exerts diverse physiological effects, such as circadian rhythm
      regulator and antioxidant. However, the functional importance of melatonin in
      spermatogenesis regulation remains unclear. The objectives of this study are to:
      (1) detect melatonin affection on miRNA expression profiles in GC-1 spg cells by
      miRNA deep sequencing (DeepSeq) and (2) define melatonin affected miRNA-mRNA
      interactions and associated biological processes using bioinformatics analysis.
      GC-1 spg cells were cultured with melatonin (10-7M) for 24h. DeepSeq data were
      validated using quantitative real-time reverse transcription polymerase chain
      reaction analysis (qRT-PCR). A total of 176 miRNA expressions were found to be
      significantly different between two groups (fold change of >2 or <0.5 and
      FDR<0.05). Among these expressions, 171 were up-regulated, and 5 were down
      regulated. Ontology analysis of biological processes of these targets indicated a
      variety of biological functions. Pathway analysis indicated that the predicted
      targets were involved in cancers, apoptosis and signaling pathways, such as VEGF,
      TNF, Ras and Notch. Results implicated that melatonin could regulate the
      expression of miRNA to perform its physiological effects in GC-1 spg cells. These
      results should be useful to investigate the biological function of miRNAs
      regulated by melatonin in spermatogenesis and testicular germ cell tumor.

PMID- 29197589
TI  - SIRT6 expression and oxidative DNA damage in individuals with prediabetes and
      type 2 diabetes mellitus.
AB  - Sirtuins (SIRTs) is a family of NAD+ dependent histone deacetylases. SIRT6 takes
      play in glucose homeostasis, genomic stability and DNA repair. Although increased
      oxidative DNA damage and decreased DNA repair activity were determined in
      diabetes mellitus, the possible relation between level of oxidative DNA damage
      and SIRT6 expression has not been investigated so far. We determined SIRT6
      expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of
      oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes
      mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood
      leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and
      40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time-
      polymerase chain reaction. SIRT6 protein was detected by immunocytochemical
      staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by
      ELISA. There was no significant difference between groups for SIRT6 mRNA level.
      SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM
      group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in
      comparison to control group (P<0.01 for both), however, when study groups were
      subdivided into two groups according to their age, the difference between preDM
      and control groups disappeared in both mid-aged and old-aged groups. The urinary
      8-OHdG level was found to be higher in the T2DM group in comparison to preDM
      group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the
      T2DM group was found to be higher than those in both preDM and control groups in
      the old-aged cases but no significant difference was determined between groups in
      the mid-aged cases. There was no relation between SIRT6 expression and urinary 8
      OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM
      but this effect seems to be independent from repair of oxidative DNA damage.

PMID- 29197590
TI  - Identification and expression patterns of adipokine genes during adipocyte
      differentiation in the Tibetan goat (Capra hircus).
AB  - Adipokines are secreted by adipose tissue and play an important role in the
      regulation of lipid metabolism. However, the information regarding adipokines in
      goats is limited. PPARgamma is a key gene in adipocyte differentiation and
      activates adipokine genes. Rosiglitazone is a PPARgamma agonist and can promote
      the expression of PPARgamma to increase the expression of lipogenesis-related
      genes. Therefore, investigation of the relationship between rosiglitazone and
      adipokines will help us to better understand the function of PPARgamma in lipid
      metabolism in Tibetan goats. In this study, we cloned the resistin (RETN), apelin
      (APLN), fibroblast growth factor 21 (FGF21), and visfatin (NAMPT) genes from non
      pregnant female Tibetan goat adipose tissue. APLN and NAMPT were predominantly
      expressed in the kidney, and FGF21 was expressed at the highest levels in the
      liver in vivo. In fat tissues, the highest expression levels of FGF21 and RETN
      were detected in omental fat, whereas their expression in perirenal and
      subcutaneous fat was extremely weak. APLN and NAMPT were abundantly expressed in
      omental and subcutaneous fat in vivo. In addition, the four adipokines had
      different expression profiles during goat adipocyte differentiation in vitro. Oil
      red O staining showed that rosiglitazone could promote adipocyte differentiation
      and lipid droplet formation. In addition, rosiglitazone significantly increased
      the expression of FGF21 and RETN (p<0.05) but decreased the expression of APLN
      and NAMPT (p<0.05). These results suggest that the four adipocytokine genes may
      have different roles during goat adipocyte differentiation. And PPARgamma could
      regulate the expression of the four adipokines, but the detailed regulatory
      mechanism still needs to be elucidated.

PMID- 29197591
TI  - Enhanced chondrogenesis of human bone marrow mesenchymal Stem Cell (BMSC) on
      nanofiber-based polyethersulfone (PES) scaffold.
AB  - Mesenchymal stem cells (MSC) from bone marrow hold great potential as a cell
      source for cartilage repair. The objective of our study was differentiation of
      MSC toward chondrocyte by using Nanofiber-based polyethersulfone (PES) scaffold
      and also enhanced chondrogenic differentiation of BMSC in vitro. MSCs were
      harvested from bone marrow of human and PES scaffold was fabricated via
      Electrospinning. The isolated cells were cultured on the PES scaffold and
      scaffold free method. After 21days, Real-time PCR was performed to evaluate the
      cartilage-specific genes in the mRNA levels. Also, in order to confirm our
      results, we have done immunocytochemistry and SEM imaging. Flowcytometry
      confirmed the nature of the isolated adherent cells. Immunocytochemistry and SEM
      imaging confirmed the differentiation of MSC toward chondrocyte. Also, real time
      PCR showed a significant increased gene expression of collagen type II and
      aggrecan on the PES scaffold method when compared to the mRNA levels measured in
      scaffold free method. Down regulation of Collagen type I was observed in PES
      scaffold compared to scaffold free at day 21. Also, both methods showed a similar
      pattern of expression of SOX9. Our results showed that PES scaffold maintains
      BMSC proliferation and differentiation, and can significantly enhance
      chondrogenic differentiation of BMSC. PES scaffold seeded BMSC showed the highest
      capacity for differentiation into chondrocyte-like cells.

PMID- 29197592
TI  - Porcine enterocyte protein Btnl5 negatively regulates NF-kappa B pathway by
      interfering p65 nuclear translocation.
AB  - Porcine butyrophilin-like 5 (Btnl5) is a novel member of the butyrophilin family,
      which consists of immune regulators. The expression pattern and the function of
      this gene remain unclear. In this study, Btnl5 is identified as a negative
      regulator of the NF-kappaB pathway. Our study indicates that Btnl5 is mainly
      expressed in intestinal epithelial cells (IECs) and expressed in membrane
      systems. Btnl5 inhibits MyD88-mediated activation of the NF-kappaB pathway. Btnl5
      interacts with TNF receptor-associated factor 2 (TRAF2) and transcription factor
      p65. Besides, Btnl5 inhibits p65-mediated activation of the NF-kappaB pathway and
      inhibits nuclear translocation of p65. These results suggest that Btnl5 may
      inhibit NF-kappaB pathway through binding and interfere nuclear translocation of
      p65.

PMID- 29197593
TI  - Nanoparticle-mediated cryosurgery for tumor therapy.
AB  - Cryosurgery is an energy-based surgical technique. It is minimally invasive and
      has fewer side effects than surgical resection. However, its insufficient
      freezing to target tumor and unavoidable injury to healthy tissue have restricted
      its success. Nano-cryosurgery is the combination of cryogenic biomedicine and
      nanotechnology. Its principle is to introduce a nanoparticle solution into target
      tissues to maximize heat transfer, lower the end temperature, increase ice ball
      formation, and prevent healthy tissues from being frozen. This review covers
      common nanoplatforms for nano-cryosurgery. The characteristics, advantages,
      potential challenges, future prospects of applying nano-cryosurgery are discussed
      in detail.

PMID- 29197594
TI  - Fast and non-invasive serum detection technology based on surface-enhanced Raman
      spectroscopy and multivariate statistical analysis for liver disease.
AB  - This study explored a rapid and nondestructive liver disease detection technique
      based on surface-enhanced Raman spectroscopy (SERS) to realize the early
      diagnosis, prevention, and treatment of liver disease. SERS signals of serum were
      obtained from 304 normal individuals, 333 patients with hepatopathy, and 99
      patients with esophageal cancer. The Raman spectra of different diseases were
      compared and diagnostic models of liver disease were established using orthogonal
      partial least squares discriminant analysis (OPLS-DA). The classification
      efficiencies of the different models were comprehensively evaluated through the
      receiver operating characteristic (ROC) curve and ten-fold cross validation. Area
      under the ROC curve is of greater than 0.97, indicating excellent classification
      of the groups. The accuracy rate of the test set reached 95.33%, and the lowest
      was 81.76% using the ten-fold cross validation. Thus, OPLS-DA combined with serum
      SERS is a rapid and non-invasive technique for the diagnosis of liver disease.

PMID- 29197595
TI  - Redescription of the genus Afrodiplozoon Khotenovski, 1981 and its only known
      species Afrodiplozoon polycotyleus (Paperna, 1973) (Monogenea: Diplozoidae) using
      a combined multidisciplinary approach.
AB  - The present study redescribes the monotypic genus Afrodiplozoon Khotenovski,
      1981, a diplozooid parasite endemic to Africa, based on material collected during
      surveys carried out in the Limpopo Province, South Africa, from two cyprinid
      hosts Labeobarbus marequensis and Enteromius paludinosus. Morphometrical analysis
      of the composition of internal organs and attachment clamps, using light
      microscopy and scanning electron microscopy, provided details for the genus and
      species redescriptions. Posterior attachment apparatus can bear up the 15 pairs
      of the clamps with the first pair of clamps distinctly smaller and not fully
      developed. Molecular characterization of the second internal transcribed spacer
      (ITS2) rDNA and phylogenetic analysis revealed the position of Afrodiplozoon
      polycotyleus as a sister taxon to Paradiplozoon krugerense and Paradiplozoon
      bingolenisis, distant from other African representatives of the genus
      Paradiplozoon, Paradiplozoon vaaleense and Paradiplozoon ichtyoxanthon.

PMID- 29197596
TI  - Historical review and insights on the livestock tick-borne disease research of a
      developing country: The Philippine scenario.
AB  - Tick-borne diseases (TBDs) remain to be a global animal health threat. Developing
      countries like the Philippines is not exempt to this. Despite the potential
      impact TBDs can give to these countries, local government initiatives and
      researches remain to be limited. In the Philippines, most epidemiological studies
      were confined only to specific areas, and predominantly in the Northern Area. Due
      to its unique geography and limited studies, the current nationwide status of
      most TBDs could not be clearly established. This review mainly covered published
      studies and presented challenges in the conduct of TBD research in the
      Philippines, which may be similar to other Southeast Asian or developing
      countries. To date, reported livestock TBD pathogens in the Philippines include
      Anaplasma, Babesia, Theileria, and Mycoplasma spp. With the ubiquitous presence
      of the Rhipicephalus microplus ticks in the country, it is highly probable that
      other pathogens transmitted by these vectors could be present. Despite studies on
      different TBDs in the livestock sector, the Philippine government has not yet
      heightened its efforts to implement tick control measures as part of the routine
      animal health program for local farmers. Further studies might be needed to
      determine the nationwide prevalence of TBDs and the presence of other possible
      tick species and TBD pathogens. The Philippine scenario may present situations
      that are similar to other developing countries.

PMID- 29197597
TI  - Why should the two-thumb technique be used for infant cardiopulmonary
      resuscitation?

PMID- 29197598
TI  - Effect of sedation on quantitative electroencephalography after cardiac arrest.
AB  - BACKGROUND: Electroencephalography (EEG) has clinical and prognostic importance
      after cardiac arrest (CA). Recently, interest in quantitative EEG (qEEG) analysis
      has grown. The qualitative effects of sedation on EEG are well known, but
      potentially confounding effects of sedatives on qEEG after anoxic injury are
      poorly characterized. We hypothesize that sedation increases suppression ratio
      (SR) and decreases alpha/delta ratio (ADR) and amplitude-integrated EEG (aEEG),
      and that the magnitude of sedation effects will be associated with outcome.
      METHODS: We routinely monitor comatose post-arrest patients with EEG for 48-72h.
      We included comatose EEG-monitored patients after CA who had protocolized daily
      sedation interruptions. We used Persyst v12 to quantify qEEG parameters and
      calculated medians for 10min immediately prior to sedation interruption and for
      the last 5min of interruption. We used paired t-tests to determine whether qEEG
      parameters changed with sedation cessation, and logistic regression to determine
      whether these changes predicted functional recovery or survival at discharge.
      RESULTS: 78 subjects were included (median age 56, 65% male). Interruptions
      occurred a median duration of 34h post-arrest and lasted a median duration of
      60min. Prior to interruption, higher aEEG predicted survival, while lower SR
      predicted both survival and favorable outcome. During interruption, SR decreased
      (p<0.001), aEEG increased (p=0.002), and ADR did not change. Larger decreases in
      SR predicted decreased survival (OR=1.04 per percent change; 95% CI 1.00-1.09).
      CONCLUSION: Higher aEEG and lower SR predict survival after CA. Sedation alters
      aEEG and SR, but importantly does not appear to affect the relationship between
      these parameter values and outcome.

PMID- 29197599
TI  - Meningococcal carriage within households in the African meningitis belt: A
      longitudinal pilot study.
AB  - OBJECTIVES: Carriers of Neisseria meningitidis are a key source of transmission.
      In the African meningitis belt, where risk of meningococcal disease is highest, a
      greater understanding of meningococcal carriage dynamics is needed. METHODS: We
      randomly selected an age-stratified sample of 400 residents from 116 households
      in Bamako, Mali, and collected pharyngeal swabs in May 2010. A month later, we
      enrolled all 202 residents of 20 of these households (6 with known carriers) and
      collected swabs monthly for 6 months prior to MenAfriVac vaccine introduction and
      returned 10 months later to collect swabs monthly for 3 months. We used standard
      bacteriological methods to identify N. meningitidis carriers and fit hidden
      Markov models to assess acquisition and clearance overall and by sex and age.
      RESULTS: During the cross-sectional study 5.0% of individuals (20/400) were
      carriers. During the longitudinal study, 73 carriage events were identified from
      1422 swabs analyzed, and 16.3% of individuals (33/202) were identified as
      carriers at least once. The majority of isolates were non-groupable; no serogroup
      A carriers were identified. CONCLUSIONS: Our results suggest that the duration of
      carriage with any N. meningitidis averages 2.9 months and that males and children
      acquire and lose carriage more frequently in an urban setting in Mali. Our study
      informed the design of a larger study implemented in seven countries of the
      African meningitis belt.

PMID- 29197600
TI  - Alveolar T-helper 17 responses to streptococcus pneumoniae are preserved in ART
      untreated and treated HIV-infected Malawian adults.
AB  - OBJECTIVE: We explored if HIV infection is associated with impaired T-Helper 17
      responses against Streptococcus pneumoniae in the lung. METHODS: We recruited 30
      HIV-uninfected healthy controls, 23 asymptomatic HIV-infected adults not on ART,
      and 40 asymptomatic HIV-infected adults on ART (Median time 3.5yrs), in whom we
      collected bronchoalveolar lavage fluid. We measured alveolar CD4+ T cell immune
      responses following stimulation with pneumococcal cell culture supernatant using
      flow cytometry-based intracellular cytokine staining. RESULTS: We found that the
      proportion of alveolar CD4+ T cells producing IL-17A following stimulation with
      pneumococcal cell culture supernatant (CCS) was similar between HIV-uninfected
      controls and ART-naive HIV-infected adults (0.10% vs. 0.14%; p = 0.9273). In
      contrast, the proportion and relative absolute counts of CD4+ T cells producing
      IL-17A in response to pneumococcal CCS were higher in ART-treated HIV-infected
      adults compared HIV-uninfected controls (0.22% vs. 0.10%, p = 0.0166; 5420 vs.
      1902 cells/100 ml BAL fluid; p = 0.0519). The increase in relative absolute
      numbers of IL-17A-producing alveolar CD4+ T cells in ART-treated individuals was
      not correlated with the peripheral blood CD4+ T cell count (r=-0.1876, p =
      0.1785). CONCLUSION: Alveolar Th17 responses against S. pneumoniae are preserved
      in HIV-infected adults. This suggests that there are other alternative mechanisms
      that are altered in HIV-infected individuals that render them more susceptible to
      pneumococcal pneumonia.

PMID- 29197601
TI  - Ectopic Expression of PCSK9 by Smooth Muscle Cells Contributes to Aortic
      Dissection.
AB  - BACKGROUND: Acute aortic dissection (AAD) is a common disease among the elderly.
      Although several risk factors of AAD have been reported, the molecular mechanism
      underlying AAD development remains to be elucidated. Proprotein convertase
      subtilisin/kexin type 9 (PCSK9) increases low-density lipoprotein cholesterol
      levels in blood by preventing its clearance. Therefore, PCSK9 inhibition is a
      promising therapeutic approach to treat cardiovascular diseases (CVDs). The
      objective of this study was to elucidate the role of PCSK9 in the pathogenesis of
      AAD. METHODS: We used fluorescence immunohistochemistry to assess PCSK9
      expression in aortic tissues resected from 10 AAD patients and in the normal
      aorta from 5 autopsy samples as well as in spontaneously hyperlipidemic
      apolipoprotein E-deficient mice used as an experimental AD model. RESULTS: We
      revealed a characteristic distribution pattern of PCSK9 in atherosclerotic
      plaques and the degenerated tunica media in AAD tissues, which was rarely
      observed in normal aortic tissues. Furthermore, PCSK9 was notably expressed
      around calcification areas formed by vascular smooth muscle cells, especially
      those of the synthetic phenotype. The results obtained in the animal model were
      consistent with PCSK9 expression in AAD tissues. CONCLUSIONS: Our findings
      suggest that PCSK9 overexpression in the aorta may promote AAD. This study adds
      to the growing body of evidence supporting the use of PCSK9 inhibitors for the
      management of CVDs.

PMID- 29197602
TI  - Continuous Flow Perfused Cadaver Model for Endovascular Training, Research, and
      Development.
AB  - BACKGROUND: Endovascular simulation employing computer, animal, and static models
      are common and useful adjuncts for teaching endovascular procedures and
      developing novel, complex endovascular techniques. Unfortunately, these models
      lack realistic haptic feedback and thus do not faithfully replicate many of the
      technical challenges associated with clinical endovascular procedures (e.g.,
      arterial calcification, rigidity, and stenosis). We sought to develop a realistic
      and reproducible perfused cadaver model for endovascular training, device
      development, and research. METHODS: Fresh frozen, elderly (age 50-80 years) male
      cadavers were thawed and prepared for open dissection. The entire arterial tree
      (ascending aorta to femoral arteries) was dissected free and major branch vessels
      exposed. Sheaths were placed to allow outflow from selected vessels. A Dacron
      conduit was sewn to the ascending aorta to generate arterial inflow, which was
      provided by a centrifugal pump. Aortic aneurysms were created in the descending
      thoracic and abdominal aorta. Digital subtraction arteriography and various
      endovascular interventions were performed, including stent grafts and EndoAnchors
      deployment. RESULTS: Continuous antegrade flow was achieved in the thoracic,
      abdominal, iliac, and femoral segments. Open and percutaneous access at the
      femoral region was obtained with realistic back-bleeding and tactile feedback.
      Adequate, fluoroscopically documented flow was observed in both cannulated major
      and noncannulated smaller branches. We performed angiography with standard
      techniques via a pigtail catheter and contrast injector throughout the arterial
      system. Abdominal and thoracic endografts were deployed with appropriate
      angiographic guidance and realistic haptic feedback for both guidewire and stent
      grafts. Additional applications, including selective cannulation, aorto-iliac
      occlusive disease interventions, and anchor placement, were also successfully
      simulated. Finally, the model was used as a platform to test investigational
      devices. CONCLUSIONS: Our pressurized cadaver flow model successfully replicated
      multiple aspects of advanced endovascular procedures with haptic feedback. This
      novel human cadaver model allows for training and device development under
      clinically realistic conditions.

PMID- 29197603
TI  - A Reliable Mouse Model of Hind limb Gangrene.
AB  - BACKGROUND: Lack of a reliable hind limb gangrene animal model limits preclinical
      studies of gangrene, a severe form of critical limb ischemia. We develop a novel
      mouse hind limb gangrene model to facilitate translational studies. METHODS:
      BALB/c, FVB, and C57BL/6 mice underwent femoral artery ligation (FAL) with or
      without administration of NG-nitro-L-arginine methyl ester (L-NAME), an
      endothelial nitric oxide synthase inhibitor. Gangrene was assessed using
      standardized ischemia scores ranging from 0 (no gangrene) to 12 (forefoot
      gangrene). Laser Doppler imaging (LDI) and DiI perfusion quantified hind limb
      reperfusion postoperatively. RESULTS: BALB/c develops gangrene with FAL-only (n =
      11/11, 100% gangrene incidence), showing mean limb ischemia score of 12 on
      postoperative days (PODs) 7 and 14 with LDI ranging from 0.08 to 0.12 on
      respective PODs. Most FVB did not develop gangrene with FAL-only (n = 3/9, 33%
      gangrene incidence) but with FAL and L-NAME (n = 9/9, 100% gangrene incidence).
      Mean limb ischemia scores for FVB undergoing FAL with L-NAME were significantly
      higher than for FVB receiving FAL-only. LDI score and capillary density by POD 28
      were significantly lower in FVB undergoing FAL with L-NAME. C57BL/6 did not
      develop gangrene with FAL-only or FAL and L-NAME. CONCLUSIONS: Reproducible
      murine gangrene models may elucidate molecular mechanisms for gangrene
      development, facilitating therapeutic intervention.

PMID- 29197604
TI  - Atherectomy-Associated Complications in the Southern California Vascular Outcomes
      Improvement Collaborative.
AB  - BACKGROUND: Atherectomy has become an increasingly utilized modality for the
      endovascular treatment of peripheral arterial occlusive disease. The objective of
      this study was to determine the incidence and risk factors for atherectomy
      associated complications. METHODS: A retrospective review was performed for all
      atherectomy procedures performed between January 2011 and December 2015 in the
      Southern California Vascular Outcomes Improvement Collaborative. Atherectomy was
      defined as laser, orbital, or excisional atherectomy. Complications were
      dissection, perforation, and distal embolization. RESULTS: Seven hundred twenty
      nine atherectomy procedures were performed at 7 institutions by 27 practitioners.
      The mean age was 73 years with 415 (57%) males. Four hundred nineteen (57%) were
      diabetic, 673 (92%) hypertensive, 457 (63%) smokers, and 244 (34%) had coronary
      artery disease. Dissection occurred in 51 (7%) procedures, embolization in 23
      (3.1%), and perforation in 12 (1.6%). The mean number of lesions treated per
      artery was the same at 1.6 in patients with any complication and no complication
      (P = 0.77). The total occluded length was 7.4 cm for complications versus 7.2 cm
      for no complication (P = 0.73). The total treated length was 12.9 cm for
      complications versus 11.3 cm for no complication (P = 0.03). The incidence of
      complications for Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions were
      13% compared to 10% for TASC A/B lesions (P = 0.05). The incidence of
      complications in superficial femoral/popliteal lesions was 12.9% vs. 10.4% in
      tibial lesions (P = 0.13). In multivariable analysis, treatment length was
      associated with a small increased risk of complication (odds ratio = 1.02, 95%
      confidence interval = 1.0-1.04). CONCLUSIONS: Increased treatment length is
      associated with an increased risk of atherectomy-associated complications.
      Demographic factors and comorbidities were not predictors of complications.

PMID- 29197605
TI  - Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of
      Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral
      Artery Bypass Model.
AB  - BACKGROUND: Bypass graft thrombosis remains a significant mode of failure in
      prosthetic graft revascularization. The purpose of this investigation was to
      evaluate the long-term thromboresistant effect of heparin-bonded expanded
      polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology
      in a canine model. METHODS: Bilateral femorofemoral artery bypass grafts with
      ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin
      bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control
      nonheparin graft was placed on the contralateral side. The graft patency was
      assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass.
      Heparin bioactivity of the graft material was analyzed. The effect of intimal
      hyperplasia was also assessed. RESULTS: All bypass grafts were patent at 1 month.
      Significantly greater patency rates were noted in the Propaten group compared to
      the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%,
      35%, and 20%, respectively (P < 0.02). There was a significant reduction in the
      anastomotic neointimal area and neointimal cell proliferation in Propaten grafts
      compared with control grafts at all groups between 6 and 24 months (P < 0.05).
      Heparin bioactivity as measured by antithrombin binding assay was demonstrated in
      the Propaten graft between 1 and 24 months. Mean heparin activities on Propaten
      grafts ranged from 26.3 +/- 6.4 pmol/cm2 to 18.4 +/- 8.7 pmol/cm2 between 1 and
      24 months, which were significantly greater than the control group (P < 0.001).
      Differences between mean heparin activities of explanted Propaten graft samples
      at the various time points were nonsignificant (P > 0.05). CONCLUSIONS: Heparin
      bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic
      intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten
      graft confers an advantage in long-term graft patency.

PMID- 29197606
TI  - Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic
      Aneurysms in Angiotensin II-Induced Mice.
AB  - BACKGROUND: Plasma low-density lipoprotein (LDL) cholesterol is implicated in
      abdominal aorta (AA) and aortic dissection (AD); however, its role in the
      pathogenesis of AA and AD, a disease with a high mortality rate, is unknown. The
      existing animal models such as apolipoprotein E-deficient (Apoe-/-) mice cannot
      reproduce all the conditions of AA/AD, including elevated LDL-cholesterol levels
      and spontaneous atheroma formation; therefore, a more reliable in vivo model is
      required. Here, we analyzed angiotensin II (Ang II)-induced mice with combined
      deficiency of the LDL receptor and the catalytic component of the apolipoprotein
      B-edisome complex (Ldlr-/-/Apobec1-/- [WKO]) to understand AA formation and AD
      occurrence in relation to plasma lipid composition. METHODS: AAs and ADs were
      created in 18- to 22- week-old male Apoe-/- and Ldlr-/-/Apobec1-/- mice by Ang II
      infusion. Immunostaining allowed assessment of smooth muscle cells and mural
      monocytes/macrophages. RESULTS: Ldlr-/-/Apobec1-/- mice had elevated LDL
      cholesterol levels characteristic for human type IIa hyperlipidemia, resulting in
      atherogenesis, which promoted mortality, AA formation, and AD development.
      Interestingly, variations in the distribution of atheromas and inflammatory sites
      between Apoe-/- and Ldlr-/-/Apobec1-/- mice depending on lipid profiles resulted
      in differences in AA formation and AD occurrence in the thoracic aorta.
      CONCLUSIONS: Our results indicate the presence of a pathogenic pathway involving
      serum lipid composition that plays a key role in AA formation and AD occurrence
      in Ang II-induced mice.

PMID- 29197607
TI  - Inflammatory Response Modulation through a PPARgamma Agonist during Surgically
      Induced Visceral Ischemia in an Animal Model.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury represents one of the most severe
      complications in vascular surgery where cross-clamping of the aorta and
      subsequent visceral ischemia are a recurrent issue. The literature describes a
      family of nuclear receptors, that is, peroxisome proliferator-activated receptors
      (PPARs), in particular PPARgamma isoform, which are important modulators of
      vascular inflammation resulting from I/R injury. The aim of our study is to
      evaluate how PPARgamma agonist administration could reduce local and systemic
      inflammatory response after I/R injury during aortic supraceliac clamping in
      animal model. METHODS: Our model includes 16 rats divided as follows: 8 rats in
      the placebo control group (PlacG) were operated on without having been
      administered of any drugs during the preoperative period, whereas the 8 rats in
      the pioglitazone group (PioG) were pretreated with pioglitazone. Renal and
      visceral ischemias were induced in the rats by supraceliac aortic clamping. Rats
      were sacrificed after surgery, and then, we collected blood samples to measure
      serum levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha)
      and one of the kidneys and a segment of the liver to perform histological
      analysis. RESULTS: Considering both cytokines in the PioG, there has been a
      negative trend in serum concentrations, whereas in the PlacG, we observed an
      increasing trend. The high standard deviation observed in our study is mainly due
      to the small population of the cohort. Histologic examination of the kidney
      showed more severe damage in the placebo group as compared to the PioG with more
      evident differences in tubular and tubulointerstitial scores. CONCLUSIONS: Our
      observations show that administering pioglitazone can partially reduce secondary
      inflammatory response in the ischemic insult especially in endothelial and
      perivascular tissues.

PMID- 29197608
TI  - Use of Double-Barrel Gore Excluder Bifurcated Endografts for Renal Artery
      Incorporation in an Urgent Endovascular Repair of a Thoracoabdominal Aortic
      Aneurysm.
AB  - Total endovascular repair of a thoracoabdominal aortic aneurysm (TAAA) in an
      urgent setting requires an advanced endovascular skill set and an innovative
      approach. We describe a novel technique of treating a symptomatic Crawford extent
      4 TAAA with a combination of multilayered parallel endografting and double-barrel
      Gore Excluder bifurcated endografts to achieve complete aneurysm exclusion with
      visceral and bilateral renal artery incorporation. A 75-year-old male presented
      with a symptomatic 10 cm Crawford extent 4 TAAA. Severe medical comorbidities,
      including chronic obstructive lung disease and cardiac arrhythmia, as well as
      prior open infrarenal aortic aneurysm repair made him high risk for an urgent re
      do open repair. His previous open infrarenal aortic replacement created a short
      distance between the lowest renal artery and the flow divider of the aortic
      graft, which posed a challenge in using a bifurcated aortic endograft as a distal
      component of the previously described multilayered parallel endografting.
      Therefore, celiac and superior mesenteric arteries were treated with a
      multilayered parallel grafting configuration, whereas bilateral renal arteries
      were incorporated using side-by-side bifurcated modular stent grafts in double
      barrel fashion. Contralateral gates served as cuffs for renal artery branch stent
      grafts, and ipsilateral limbs were deployed within the common iliac arteries. The
      patient recovered well and was discharged 3 days after repair. Follow-up imaging
      at 1 month demonstrated patent celiac, superior mesenteric, and bilateral renal
      artery flow, with no endoleak and stable aneurysm sac. The patient is doing well
      clinically 1 year after the operation.

PMID- 29197609
TI  - Comparison of 2 Sample Processing Methods and 9 Commercial Immunoassays for the
      Detection of Interleukin-1alpha in the Serum of Patients with Abdominal Aortic
      Aneurysm.
AB  - BACKGROUND: For a cytokine to have a role as a clinically useful biomarker, it
      must be measureable in a practical, reliable, and reproducible manner.
      Furthermore, assays from different manufacturers should produce comparable
      results. The aim of this paper was to examine the effect of 2 sample processing
      methodologies and compare 9 commercially available immunoassays for their
      measurement of serum interleukin (IL)-1alpha in patients with abdominal aortic
      aneurysm. METHODS: Two sample processing methodologies and 9 manufacturers'
      immunoassays were compared. Each immunoassay was also tested for detection of
      both IL-1alpha isoforms. RESULTS: A positive signal for IL-1alpha was found in
      all serum samples, in all immunoassays, using both processing methods. In the
      majority, titer concentrations were unquantifiable with values below
      manufacturers' detectable range. Variability in titer concentrations was seen
      across all immunoassays. With the exception of 1 immunoassay, all were able to
      detect both IL-1alpha isoforms. CONCLUSIONS: Researchers wishing to measure serum
      cytokines levels should be aware that differences in sample processing methods
      and manufacturers' immunoassays can affect the results. This may result in
      misleading conclusions being drawn about biological processes underpinning a wide
      range of inflammatory diseases.

PMID- 29197610
TI  - Thromboembolic Risk of Endovascular Intervention for Lower Extremity Deep Venous
      Thrombosis.
AB  - BACKGROUND: This study evaluated the risk of thromboembolism during endovascular
      interventions in patients with symptomatic lower extremity deep vein thrombosis
      (DVT) METHODS: Clinical records of all patients who underwent endovascular
      interventions for symptomatic lower extremity DVT from 2001 to 2017 were
      retrospectively analyzed using a prospectively maintained database. Only patients
      who received an inferior vena cava (IVC) filter were included in the analysis.
      Trapped intrafilter thrombus was assessed for procedure-related thromboembolism.
      Clinical outcomes of thrombus management and thromboembolism risk were analyzed.
      RESULTS: A total 172 patients (mean age 57.4 years, 98 females) who underwent 174
      endovascular DVT interventions were included in the analysis. Treatment
      strategies included thrombolytic therapy (64%), mechanical thrombectomy (n =
      86%), pharmacomechanical thrombolysis (51%), balloon angioplasty (98%), and stent
      placement (28%). Thrombectomy device used included AngioJet (56%), Trellis (19%),
      and Aspire (11%). Trapped IVC filter thrombus was identified in 58 patients (38%)
      based on the IVC venogram. No patient developed clinically evident pulmonary
      embolism (PE). IVC filter retrieval was performed in 98 patients (56%, mean 11.8
      months after implantation). Multivariate analysis showed that iliac vein
      occlusion (P = 0.04) was predictive for procedure-related thromboembolism.
      CONCLUSIONS: Iliac vein thrombotic occlusion is associated with an increased
      thromboembolic risk in DVT intervention. Retrievable IVC filter should be
      considered when performing percutaneous thrombectomy in patients with iliac
      venous occlusion to prevent PE.

PMID- 29197613
TI  - Neonatal Arch Reconstruction: Guiding Principles, Some Misguided Ones, and a Few
      More That Don't Matter.

PMID- 29197611
TI  - Overexpression of Angiopoietin-1 Potentiates Endothelial Progenitor Cells for the
      Treatment of Aneurysm.
AB  - BACKGROUND: To investigate whether angiopoietin-1 (Ang-1) could regulate the
      endothelial progenitor cells (EPCs) survival and the effect of accelerating intra
      aneurysmal organization and occlusion of the aneurysm neck. METHODS: EPCs were
      isolated from Wistar rats. EPCs were cultured and transfected with lentivirus-Ang
      1-endothelial progenitor cells (Ang-1-EPCs) and lentivirus-NC-endothelial
      progenitor cells (NC-EPCs). The effects of Ang-1 on viability and functioning of
      EPCs were explored via tube formation, migration, and MTT (3-[4,5
      dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide) assays. Eighteen Wistar
      rats were randomly allocated into 3 groups. Eighteen bare coils were inserted
      into the ligated external carotid artery (ECA) sacs of rats. The ECA sacs were
      removed 2 weeks after the coils were implanted and examined by histology assay.
      RESULTS: Ang-1 significantly promoted EPCs tube formation, migration, and
      proliferation ability in vitro. Histology analyses revealed that the organized
      areas in the ECA sacs in the Ang-1-EPCs group are higher than NC-EPCs group and
      control group at 2 weeks. Immunofluorescence revealed that organized tissues were
      characterized by an accumulation of cells positive for alpha-smooth muscle actin
      positive cells in aneurysm sacs. CONCLUSIONS: Overexpression of Ang-1 enhanced
      the tube formation, migration, and proliferation ability of EPCs. Ang-1 gene
      modified EPCs accelerated organization within the aneurysms and occlusion of
      aneurysm neck. Transplantation of Ang-1-transfected EPCs may be a new method for
      the treatment of aneurysm.

PMID- 29197612
TI  - Preoperative Cardiac Stress Testing in the Southern California Vascular Outcomes
      Improvement Collaborative.
AB  - BACKGROUND: The objective of this study was to examine the use of preoperative
      cardiac stress testing (PCST) in the Southern California Vascular Outcomes
      Improvement Collaborative (So Cal VOICe). METHODS: A retrospective review was
      performed on data in all modules of the So Cal VOICe from September 2012 through
      May 2016. PCST was defined as stress echocardiogram or nuclear stress test. A new
      postoperative myocardial infarction (MI) was defined as troponin elevation and/or
      electrocardiogram/imaging changes with or without ischemic symptoms. Only
      elective cases in patients with asymptomatic cardiac status were included in the
      study. RESULTS: During the study period, 3,063 procedures meeting the inclusion
      criteria were performed in 7 registries: carotid endarterectomy (CEA), carotid
      artery stent, thoracic endovascular aneurysm repair, infrainguinal bypass
      (Infra), endovascular aneurysm repair (EVAR), suprainguinal bypass (Supra), and
      open abdominal aortic aneurysm repair (OAAA). PCST varied across registries from
      17% in PVI to 62% in OAAA. PCST in CEA varied across 9 institutions from 10% to
      79%. PCST in EVAR varied across 7 institutions from 14% to 83%. PCST in Infra
      varied across 4 institutions from 10% to 57%. Of the 12 patients across all
      registries who had a new MI, 6 had PCST, one of which was abnormal. CONCLUSIONS:
      The incidence of PCST varies widely across registries and institutions in the So
      Cal VOICe. Despite the wide variation, the incidence of new postoperative MI is
      exceptionally low. Further studies should evaluate the cost-effectiveness of the
      PCST practices and future quality improvement efforts should focus on
      standardization of indications for PCST.

PMID- 29197614
TI  - An anatomical and physiological basis for the cardiovascular autonomic nervous
      system consequences of sport-related brain injury.
AB  - Concussion is defined as a complex pathophysiological process affecting the brain
      that is induced by the application or transmission of traumatic biomechanical
      forces to the head. The result of the impact is the onset of transient symptoms
      that may be experienced for approximately 2weeks in most individuals. However, in
      some individuals, symptoms may not resolve and persist for a protracted period
      and a chronic injury ensues. Concussion symptoms are generally characterized by
      their emergence through changes in affect, cognition, or multi-sensory processes
      including the visual and vestibular systems. An emerging consequence of
      concussion is the presence of cardiovascular autonomic nervous system dysfunction
      that is most apparent through hemodynamic perturbations and provocations. Further
      interrogation of data that are derived from continuous digital electrocardiograms
      and/or beat-to-beat blood pressure monitoring often reveal an imbalance of
      parasympathetic or sympathetic nervous system activity during a provocation after
      an injury. The disturbance is often greatest early after injury and a resolution
      of the dysfunction occurs in parallel with other symptoms. The possibility exists
      that the disturbance may remain if the concussion does not resolve.
      Unfortunately, there is little evidence in humans to support the etiology for the
      emergence of this post-injury dysfunction. As such, evidence from experimental
      models of traumatic brain injury and casual observations from human studies of
      concussion implicate a transient abnormality of the anatomical structures and
      functions of the cardiovascular autonomic nervous system. The purpose of this
      review article is to provide a mechanistic narrative of multi-disciplinary
      evidence to support the anatomical and physiological basis of cardiovascular
      autonomic nervous system dysfunction after concussion. The review article will
      identify the anatomical structures of the autonomic nervous system and propose a
      theoretical framework to demonstrate the potential effects of concussive head
      trauma on corresponding outcome measurements. Evidence from experimental models
      will be used to describe abnormal cellular functions and provide a hypothetical
      mechanistic basis for the respective responses of the anatomical structures to
      concussive head trauma. When available, example observations from the human
      concussion literature will be presented to demonstrate the effects of concussive
      head trauma that may be related to anomalous activity in the respective
      anatomical structures of the autonomic nervous system.

PMID- 29197615
TI  - Interplay between the lung microbiome and lung cancer.
AB  - The human microbiome confers benefits or disease susceptibility to the human body
      through multiple pathways. Disruption of the symbiotic balance of the human
      microbiome is commonly found in systematic diseases such as diabetes, obesity,
      and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of
      the microbiota may also play vital roles in carcinogenesis at multiple levels,
      e.g., by affecting metabolic, inflammatory, or immune pathways. Although the
      impact of the gut microbiome on the digestive cancer has been widely explored,
      few studies have investigated the interplay between the microbiome and lung
      cancer. Some recent studies have shown that certain microbes and microbiota
      dysbiosis are correlated with development of lung cancer. In this mini-review, we
      briefly summarize current research findings describing the relationship between
      the lung microbiome and lung cancer. We further discuss the potential mechanisms
      through which the lung microbiome may play a role in lung carcinogenesis and
      impact lung cancer treatment. A better knowledge of the interplay between the
      lung microbiome and lung cancer may promote the development of innovative
      strategies for early prevention and personalized treatment in lung cancer.

PMID- 29197616
TI  - The effect of monitor raster latency on VEPs, ERPs and Brain-Computer Interface
      performance.
AB  - BACKGROUND: Visual neuroscience experiments and Brain-Computer Interface (BCI)
      control often require strict timings in a millisecond scale. As most experiments
      are performed using a personal computer (PC), the latencies that are introduced
      by the setup should be taken into account and be corrected. As a standard
      computer monitor uses a rastering to update each line of the image sequentially,
      this causes a monitor raster latency which depends on the position, on the
      monitor and the refresh rate. NEW METHOD: We technically measured the raster
      latencies of different monitors and present the effects on visual evoked
      potentials (VEPs) and event-related potentials (ERPs). Additionally we present a
      method for correcting the monitor raster latency and analyzed the performance
      difference of a code-modulated VEP BCI speller by correcting the latency.
      COMPARISON WITH EXISTING METHODS: There are currently no other methods validating
      the effects of monitor raster latency on VEPs and ERPs. RESULTS: The timings of
      VEPs and ERPs are directly affected by the raster latency. Furthermore,
      correcting the raster latency resulted in a significant reduction of the target
      prediction error from 7.98% to 4.61% and also in a more reliable classification
      of targets by significantly increasing the distance between the most probable and
      the second most probable target by 18.23%. CONCLUSIONS: The monitor raster
      latency affects the timings of VEPs and ERPs, and correcting resulted in a
      significant error reduction of 42.23%. It is recommend to correct the raster
      latency for an increased BCI performance and methodical correctness.

PMID- 29197617
TI  - 3-D motion capture for long-term tracking of spontaneous locomotor behaviors and
      circadian sleep/wake rhythms in mouse.
AB  - BACKGROUND: Locomotor activity provides an index of an animal's behavioral state.
      Here, we report a reliable and cost-effective method that allows long-term (days
      to months) simultaneous tracking of locomotion in mouse cohorts (here consisting
      of 24 animals). NEW METHOD: The technique is based on a motion capture system
      used mainly for human movement study. A reflective marker was placed on the head
      of each mouse using a surgical procedure and labeled animals were returned to
      their individual home cages. Camera-recorded data of marker displacement
      resulting from locomotor movements were then analyzed with custom built software.
      To avoid any data loss, data files were saved every hour and automatically
      concatenated. Long-term recordings (up to 3 months) with high spatial (<1mm) and
      temporal (up to 100Hz) resolution of animal movements were obtained. RESULTS: The
      system was validated by analyzing the spontaneous activity of mice from post
      natal day 30-90. Daily motor activity increased up to 70days in correspondence
      with maturational changes in locomotor performance. The recorded actigrams also
      permitted analysis of circadian and ultradian rhythms in cohort sleep/wake
      behavior. COMPARISON WITH EXISTING METHOD(S): In contrast to traditional session
      based experimental approaches, our technique allows locomotor activity to be
      recorded with minimal experimenter manipulation, thereby minimizing animal
      stress. CONCLUSIONS: Our method enables the continuous long-term (up to several
      months) monitoring of tens of animals, generating manageable amounts of data at
      minimal costs without requiring individual dedicated devices. The actigraphic
      data collected allows circadian and ultradian analysis of sleep/wake behaviors to
      be performed.

PMID- 29197618
TI  - Chlorella sp. transgenic with Scy-hepc enhancing the survival of Sparus
      macrocephalus and hybrid grouper challenged with Aeromonas hydrophila.
AB  - Two marine antimicrobial peptides (AMPs), PC-hepc from large yellow croaker
      (Pseudosciaena crocea) and scygonadin from mud crab (Scylla serrata), are
      potently active against specific bacteria and thus they could be used as
      substitutes for antibiotics in aquaculture. However, how to utilize the AMPs
      feasibly for marine cultured animals has been so far confused. In our study, a
      510 bp of the Scy-hepc sequence was cloned into pMDC85 expression vector, which
      was then electroporated into Chlorella sp., and thus a transgenic Chlorella, in
      which the Scy-hepc gene was effectively expressed, was developed. The Scy-hepc
      fusion protein was successfully expressed in Chlorella sp. and it showed obvious
      bactericidal activity. In addition, the in vivo efficacy of the transgenic
      Chlorella was evaluated using Sparus macrocephalus and the hybrid Epinephelus
      fuscoguttatus (?) * Epinephelus lanceolatus (?). Results showed that the survival
      rate of S. macrocephalus fed with transgenic Chlorella (80 +/- 10% after 72 h)
      was significantly higher than that of fish fed with the same dosage of wild-type
      Chlorella (33.33 +/- 11.55% after 72 h). Similarly, results showed that the
      survival rate of the hybrid grouper fed with transgenic Chlorella (55 +/- 5%
      after 36 h) was much higher than that of fish fed with the same dosage of wild
      type Chlorella (25 +/- 5% after 36 h). Therefore, in vitro and in vivo results
      indicated that the constructed transgenic Chlorella with the marine AMPs Scy-hepc
      could exert effective protection for fish against the Aeromonas hydrophila
      infection, providing an encouraging prospect for the expected use of transgenic
      Chlorella in aquaculture in future.

PMID- 29197619
TI  - Harnessing CRISPR/Cas systems for programmable transcriptional and post
      transcriptional regulation.
AB  - Genome editing has enabled broad advances and novel approaches in studies of gene
      function and structure; now, emerging methods aim to precisely engineer post
      transcriptional processes. Developing precise, efficient molecular tools to alter
      the transcriptome holds great promise for biotechnology and synthetic biology
      applications. Different approaches have been employed for targeted degradation of
      RNA species in eukaryotes, but they lack programmability and versatility, thereby
      limiting their utility for diverse applications. The CRISPR/Cas9 system has been
      harnessed for genome editing in many eukaryotic species and, using a
      catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed
      for transcriptional regulation. Recent studies have used other CRISPR/Cas systems
      for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a
      Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and
      used for manipulation of RNA. Here, we discuss different modalities for targeted
      RNA interference with an emphasis on the potential applications of CRISPR/Cas
      systems as programmable transcriptional regulators for broad uses, including
      functional biology, biotechnology, and synthetic biology applications.

PMID- 29197621
TI  - Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced
      peripheral neuropathies and inhibits tumor growth.
AB  - As cancer is becoming more and more a chronic disease, a large proportion of
      patients is confronted with devastating side effects of certain anti-cancer
      drugs. The most common neurological complications are painful peripheral
      neuropathies. Chemotherapeutics that interfere with microtubules, including plant
      derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced
      peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation
      and pain reduction rather than prevention of the neuropathy. The aim of this
      study was to investigate the potential of specific histone deacetylase 6 (HDAC6)
      inhibitors as a preventive therapy for CIPN using multiple rodent models for
      vincristine-induced peripheral neuropathies (VIPN). HDAC6 inhibition increased
      the levels of acetylated alpha-tubulin in tissues of rodents undergoing
      vincristine-based chemotherapy, which correlates to a reduced severity of the
      neurological symptoms, both at the electrophysiological and the behavioral level.
      Mechanistically, disturbances in axonal transport of mitochondria is considered
      as an important contributing factor in the pathophysiology of VIPN. As
      vincristine interferes with the polymerization of microtubules, we investigated
      whether disturbances in axonal transport could contribute to VIPN. We observed
      that increasing alpha-tubulin acetylation through HDAC6 inhibition restores
      vincristine-induced defects of axonal transport in cultured dorsal root ganglion
      neurons. Finally, we assured that HDAC6-inhibition offers neuroprotection without
      interfering with the anti-cancer efficacy of vincristine using a mouse model for
      acute lymphoblastic leukemia. Taken together, our results emphasize the
      therapeutic potential of HDAC6 inhibitors with beneficial effects both on
      vincristine-induced neurotoxicity, as well as on tumor proliferation.

PMID- 29197622
TI  - Protective effects of dioscin against fructose-induced renal damage via adjusting
      Sirt3-mediated oxidative stress, fibrosis, lipid metabolism and inflammation.
AB  - In the present work, the effects and possible mechanisms of dioscin, one natural
      product from the famous vegetable Dioscoreae rhizoma (Shanyao in Chinese),
      against high fructose-induced renal injury in rats were tested. The results
      showed that dioscin significantly restored fructose-induced renal injury by
      decreasing the levels of Cr, BUN, and rehabilitating histopathological changes.
      In addition, dioscin markedly adjusted the levels of MDA, SOD and GSH-Px, reduced
      ROS level in renal tissue, and decreased the levels of TG, FFA, alpha-SMA and
      COL1A. Mechanistic study showed that dioscin significantly up-regulated the
      expression levels of Sirt3, SOD2, and then suppressed inflammation by decreasing
      the expression levels of NF-kB, HMGB1, c-Jun, c-Fos, COX2, TNF-alpha, IL-1beta
      and IL-6. Furthermore, dioscin-caused high levels of Sirt3 and SOD2 attenuated
      oxidative stress by regulating the expression levels of Nrf2, GST, Keap1,
      regulated lipid metabolism by controlling the expression levels of SREBP-1c, SCD
      1, FASn, ACC, CPT1, and adjusted TGF-beta1/Smad signal to inhibit renal fibrosis.
      In summary, dioscin showed protective effects against fructose-induced renal
      damage via adjusting Sirt3-mediated oxidative stress, renal fibrosis, lipid
      metabolism and inflammation, which should be considered as one candidate to treat
      renal injury in the future. We also suggest that the patients with renal injury
      can take more Shanyao for the therapy and treatment.

PMID- 29197620
TI  - Role of the Fyn-PKCdelta signaling in SE-induced neuroinflammation and
      epileptogenesis in experimental models of temporal lobe epilepsy.
AB  - Status epilepticus (SE) induces neuroinflammation and epileptogenesis, but the
      mechanisms are not yet fully delineated. The Fyn, a non-receptor Src family
      tyrosine kinase (SFK), and its immediate downstream target, PKCdelta are emerging
      as potential mediators of neuroinflammation. In order to first determine the role
      of Fyn kinase signaling in SE, we tested the efficacy of a SFK inhibitor,
      saracatinib (25mg/kg, oral) in C57BL/6J mouse kainate model of acute seizures.
      Saracatinib pretreatment dampened SE severity and completely prevented mortality.
      We further utilized fyn-/- and fyn+/+ mice (wildtype control for the fyn-/- mice
      on same genetic background), and the rat kainate model, treated with saracatinib
      post-SE, to validate the role of Fyn/SFK in SE and epileptogenesis. We observed
      significant reduction in SE severity, epileptiform spikes, and electrographic non
      convulsive seizures in fyn-/- mice when compared to fyn+/+ mice. Interestingly,
      significant reductions in phosphorylated pSrc-416 and PKCdelta (pPKCdelta-507)
      and naive PKCdelta were observed in fyn-/- mice as compared to fyn+/+ mice
      suggesting that PKCdelta signaling is a downstream mediator of Fyn in SE and
      epileptogenesis. Notably, fyn-/- mice also showed a reduction in key
      proinflammatory mediators TNF-alpha, IL-1beta, and iNOS mRNA expression; serum IL
      6 and IL-12 levels; and nitro-oxidative stress markers such as 4-HNE, gp91phox,
      and 3-NT in the hippocampus. Immunohistochemistry revealed a significant increase
      in reactive microgliosis and neurodegeneration in the hippocampus and hilus of
      dentate gyrus in fyn+/+ mice in contrast to fyn-/- mice. Interestingly, we did
      not observe upregulation of Fyn in pyramidal neurons of the hippocampus during
      post-SE in fyn+/+ mice, but it was upregulated in hilar neurons of the dentate
      gyrus when compared to naive control. In reactive microglia, both Fyn and
      PKCdelta were persistently upregulated during post-SE suggesting that Fyn
      PKCdelta may drive neuroinflammation during epileptogenesis. Since disabling the
      Fyn kinase prior to SE, either by treating with saracatinib or fyn gene knockout,
      suppressed seizures and the subsequent epileptogenic events, we further tested
      whether Fyn/SFK inhibition during post-SE modifies epileptogenesis. Telemetry
      implanted, SE-induced, rats were treated with saracatinib and continuously
      monitored for a month. At 2h post-diazepam, the saracatinib (25mg/kg) or the
      vehicle was administered orally and repeated twice daily for first three days
      followed by a single dose/day for the next four days. The saracatinib post
      treatment prevented epileptogenesis in >50% of the rats and significantly reduced
      spontaneous seizures and epileptiform spikes in the rest (one animal did not
      respond) when compared to the vehicle treated group, which had >24 seizures in a
      month. Collectively, the findings suggest that Fyn/SFK is a potential mediator of
      epileptogenesis and a therapeutic target to prevent/treat seizures and
      epileptogenesis.

PMID- 29197623
TI  - Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and
      steroidogenesis in two experimental models.
AB  - There are reports of sulfasalazine (Salazosulfapyridine; SASP)-induced
      reproductive toxicity, but there it is not known whether the SASP molecule or its
      intestinal metabolites are responsible for this effect. Rats received SASP (150,
      300, and 600mg/kg) for 60 consecutive days (in vivo). Additionally, epididymal
      sperm was isolated and incubated with SASP (10MUM-1600MUM) (in vitro). Markers of
      oxidative stress, mitochondrial function, and sperm functionality, along with
      testis histopathology as well as several steroidogenic genes and proteins,
      including steroidogenic acute regulatory (StAR) protein, cytochrome P450 side
      chain cleavage enzyme (P450scc; Cyp11a), 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were measured. SASP
      toxicity was evident as shown by severe testicular histopathological alterations,
      along with poor sperm parameters and increased markers of oxidative stress.
      Plasma testosterone level and steroidogenesis-related gene and protein (StAR, 3
      beta-HSD, 17-beta-HSD) expressions, as well as mitochondrial membrane potential,
      were significantly decreased at high doses of SASP (in vivo). Interestingly, in
      vitro treatment of sperm with SASP not only caused no significant detrimental
      effect on rat sperm but also increased parameters of sperm functionality and
      decreased markers of oxidative stress. SASP had paradoxical actions on the rat
      sperm in these experimental models. The findings might be useful in understanding
      the mechanism(s) of SASP-induced reproductive toxicity. The present findings have
      opened a new molecular window into the relationship between disrupted
      steroidogenesis and mammalian reproduction indices and also are vital regarding
      clinical administration of SASP and human reproductive health.

PMID- 29197624
TI  - Intravascular hemolysis induced by phospholipases A2 from the venom of the
      Eastern coral snake, Micrurus fulvius: Functional profiles of hemolytic and non
      hemolytic isoforms.
AB  - A unique feature of the venom of Micrurus fulvius (Eastern coral snake) is its
      ability to induce severe intravascular hemolysis in particular species, such as
      dogs or mice. This effect was previously shown to be induced by distinct
      phospholipase A2 (PLA2) isoforms which cause direct hemolysis in vitro, an
      uncommon finding for such enzymes. The functional profiles of PLA2-17, a direct
      hemolytic enzyme, and PLA2-12, a co-existing venom isoform lacking such effect,
      were compared. The enzymes differed not only in their ability to cause
      intravascular hemolysis: PLA2-17 additionally displayed lethal, myotoxic, and
      anticoagulant actions, whereas PLA2-12 lacked these effects. PLA2-12 was much
      more active in hydrolyzing a monodisperse synthetic substrate than PLA2-17, but
      the catalytic activity of latter was notably higher on a micellar substrate, or
      towards pure phospholipid artificial monolayers under controlled lateral
      pressures. Interestingly, PLA2-17 could hydrolyze substrate at a pressure of 20
      mN m-1, in contrast to PLA2-12 or the non-toxic pancreatic PLA2. This suggests
      important differences in the monolayer penetrating power, which could be related
      to differences in toxicity. Comparative examination of primary structures and
      predicted three-dimensional folding of PLA2-12 and PLA2-17, revealed that
      differences concentrate in their N-terminal and central regions, leading to
      variations of the surface properties at the membrane interacting interface. PLA2
      17 presents a less basic interfacial surface than PLA2-12, but more bulky
      aromatic residues, which could be associated to its higher membrane-penetrating
      strength. Altogether, these structural and functional comparative observations
      suggest that the ability of PLA2s to penetrate substrate interfaces could be a
      major determinant of toxicity, perhaps more important than protein surface
      charge.

PMID- 29197625
TI  - Chemical warfare agents. Classes and targets.
AB  - Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been
      developed as chemical warfare agents in the last century. At the time of their
      initial consideration as chemical weapon, only restricted knowledge existed about
      their mechanisms of action. There exist two different types of acute toxic
      action: nonspecific cytotoxic mechanisms with multiple chemo-biological
      interactions versus specific mechanisms that tend to have just a single or a few
      target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors
      that induce neurogenic inflammation. The present work briefly surveys classes and
      toxicologically relevant features of chemical warfare agents and describes
      mechanisms of toxic action.

PMID- 29197626
TI  - Microglia: Key players in neurodevelopment and neuronal plasticity.
AB  - Microglia are the primary innate immune cells in the CNS. Since their initial
      discovery and characterization, decades of research have revealed their unique
      roles not only in maintaining immune homeostasis, but also being indispensable to
      brain development and cognitive function. As such, microglia drive
      synaptogenesis, synaptic pruning, neurogenesis and neuronal activity. Microglia
      specific mutations are implicated in several neurodevelopmental disorders, and
      dysregulation of microglial function is strongly linked to several pathologies,
      including cognitive decline and Alzheimer's disease. Importantly, developmental
      insults can lead to long-term changes in microglial function that may compromise
      the ability of the adult brain to fight infections and process cognitive
      information. Adult lifestyle or injury can also lastingly influence microglial
      morphology and function. Here we highlight key research on microglia's role in
      neuronal plasticity across the lifespan.

PMID- 29197627
TI  - MiR-34a regulates mitochondrial content and fat ectopic deposition induced by
      resistin through the AMPK/PPARalpha pathway in HepG2 cells.
AB  - Resistin is an adipocyte-derived cytokine and was named for its role in the
      development of insulin resistance. Increased serum resistin levels are also
      associated with steatohepatitis and non-alcoholic fatty liver disease. In a
      previous study, resistin was observed to reduce mitochondrial content and
      upregulate miR-34a significantly in the liver. In this study, male C57BL/6 mice
      were injected with agomir-34a or control agomir, and HepG2 cells were transfected
      with miR-34a mimics or inhibitors to assess their role in resistin-induced fat
      deposition. The overexpression of miR-34a increased liver and HepG2 cell TAG
      content, decreased mitochondrial content, changed mitochondrial morphology and
      impaired mitochondrial function. In contrast, a miR-34a inhibitor significantly
      restored the TAG content and mitochondrial transmembrane potential. A study of
      transcriptional regulation revealed that C/EBPbeta is essential for upregulating
      miR-34a by resistin. Furthermore, miR-34a inhibited the PPARalpha signaling
      pathway by binding to sites in the 3'UTR of AdipoR2 genes and the AMPK pathway.
      Consequently, this increased the fat content and decreased the mitochondrial
      content in HepG2 cells. This paper reveals a novel mechanism for mitochondrial
      regulation, which suggests that normal mitochondrial content and function is
      crucial for lipid metabolism in the liver.

PMID- 29197628
TI  - Towards the application of precision medicine in Age-Related Macular
      Degeneration.
AB  - The review essentially describes genetic and non-genetic variables contributing
      to the onset and progression of exudative Age-related Macular Degeneration (AMD)
      in Italian population. In particular, AMD susceptibility within Italian
      population is contributed to by genetic variants, accounting for 23% of disease
      and non-genetic variants, accounting for 10% of AMD. Our data highlighted
      prominent differences concerning genetic and non-genetic contributors to AMD in
      our cohort with respect to worldwide populations. Among genetic variables, SNPs
      of CFH, ARMS2, IL-8, TIMP3, SLC16A8, RAD51B, VEGFA and COL8A1 were significantly
      associated with the risk of AMD in the Italian cohort. Surprisingly, other
      susceptibility variants described in European, American and Asiatic populations,
      did not reach the significance threshold in our cohort. As expected, advanced
      age, smoking and dietary habits were associated with the disease. In addition, we
      also describe a number of gene-gene and gene-phenotype interactions. In fact, AMD
      associated genes may be involved in the alteration of Bruch's membrane and
      induction of angiogenesis, contributing to exacerbate the damage caused by aging
      and environmental factors. Our review provides an overview of genetic and non
      genetic factors characterizing AMD susceptibility in Italian population,
      outlining the differences with respect to the worldwide populations. Altogether,
      these data reflect historical, geographic, demographic and lifestyle
      peculiarities of Italian population. The role of epigenetics, pharmacogenetics,
      comorbities and genetic counseling in the management of AMD patients have been
      described, in the perspective of the application of a "population-specific
      precision medicine" approach addressed to prevent AMD onset and improve patients'
      quality of life.

PMID- 29197630
TI  - Population pharmacokinetics of articaine with 1:200,000 epinephrine during third
      molar surgery and simulation of high-dose regimens.
AB  - BACKGROUND AND OBJECTIVES: Articaine is more and more used in third molar surgery
      under local anesthesia (LA). The objectives of this analysis were to characterize
      the pharmacokinetics of articaine for this type of surgery and to simulate dosing
      regimens. METHODS: Non-linear mixed-effects modeling conducted in Monolix 4.4.0
      was used to describe articaine plasma concentration-time data from 20 patients.
      Monte Carlo simulations were then performed to evaluate the probability of
      cardiotoxic target attainment (PCTA) of various dosage regimens. RESULTS:
      Articaine concentration data were best described by a linear one-compartment
      model, with an additional depot compartment for submucosal route with a zero
      order transfer to central compartment. Age and gender were found to influence
      duration transfer (Tk0) and elimination rate constant (Ke), respectively.
      Simulated maximum recommended dose regimen (7mg/kg) had a PCTA of 0%. Simulated
      higher doses of 10mg/kg and 15mg/kg had a PCTA of 0% and about 1-4%,
      respectively. CONCLUSIONS: The model adequately described the articaine
      pharmacokinetics. This is the first PK model qualified for articaine administered
      by submucosal route. The simulations suggest that maximum recommended dose
      regimen is safe concerning the cardiotoxicity in healthy patients.

PMID- 29197631
TI  - Pulmonary drug delivery to older people.
AB  - Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease
      (COPD), are common in older people. Treatment principles are well established in
      this group of patients; however, inadequate training and improper inhaler
      techniques often results in poor treatment outcomes. Healthcare professionals
      often do not have the required knowledge about the most common inhaler devices.
      Age-related conditions like cognitive ability and physical strength would also
      impact on the inhaler usage. Pharmacokinetics and pharmacodynamics may be
      affected by physiological changes, like impaired renal and hepatic functions and
      reduced lung functions. Adjusting and optimizing the inhaler device to the
      patient preferences, improvement of the drug formulation and inhalers, and using
      different adherence strategies might improve the treatment outcomes in elderly
      patients.

PMID- 29197629
TI  - Pharmacological modulation of hypoxia-induced respiratory neuroplasticity.
AB  - Hypoxia elicits complex cell signaling mechanisms in the respiratory control
      system that can produce long-lasting changes in respiratory motor output. In this
      article, we review experimental approaches used to elucidate signaling pathways
      associated with hypoxia, and summarize current hypotheses regarding the
      intracellular signaling pathways evoked by intermittent exposure to hypoxia. We
      review data showing that pharmacological treatments can enhance neuroplastic
      responses to hypoxia. Original data are included to show that pharmacological
      modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
      (AMPAR) function can reveal a respiratory neuroplastic response to a single,
      brief hypoxic exposure in anesthetized mice. Coupling pharmacologic treatments
      with therapeutic hypoxia paradigms may have rehabilitative value following
      neurologic injury or during neuromuscular disease. Depending on prevailing
      conditions, pharmacologic treatments can enable hypoxia-induced expression of
      neuroplasticity and increased respiratory motor output, or potentially could
      synergistically interact with hypoxia to more robustly increase motor output.

PMID- 29197633
TI  - Spondyloarthritis features in zymosan-induced SKG mice.
AB  - OBJECTIVES: Spondyloarthritis (SpA) encompasses a group of disorders including
      ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic
      arthritis. SpA pathogenesis is still not well understood. Animal models are
      important for studying disease mechanisms and identifying new therapeutic agents.
      Recently, a beta-glucan-induced SKG mouse was used as an animal model for SpA.
      The aim of this study was to evaluate the clinical and molecular characteristics
      of a zymosan-induced SKG mouse. METHODS: Zymosan was injected intraperitoneally
      into SKG mice. Clinical arthritis scores were measured, and fluorine-18
      fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed
      tomography (PET/CT) was performed to quantify joint inflammation. Histologic
      features of the joints, intestines, skin, and eyes were evaluated. Inflammatory
      cytokine and Wnt inhibitor expression was measured in mouse serum. RESULTS:
      Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral
      arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. 18F
      FDG uptake was significantly higher in the zymosan-treated mice compared with
      controls. The expression of tumor necrosis factor alpha, interleukin (IL)-6, and
      Dickkopf-1 increased significantly, while IL-4 and sclerostin expression
      decreased significantly in zymosan-induced mice compared with control mice.
      CONCLUSIONS: Zymosan-induced SKG mice developed articular and extra-articular
      features as well as molecular changes that resembled those of human SpA. These
      findings suggest that the zymosan-induced SKG mouse is a good animal model to
      reflect the complex features of human SpA.

PMID- 29197632
TI  - Crosstalk between autophagy and oxidative stress regulates proteolysis in the
      diaphragm during mechanical ventilation.
AB  - Mechanical ventilation (MV) results in the rapid development of ventilator
      induced diaphragm dysfunction (VIDD). While the mechanisms responsible for VIDD
      are not fully understood, recent data reveal that prolonged MV activates
      autophagy in the diaphragm, which may occur as a result of increased cellular
      reactive oxygen species (ROS) production. Therefore, we tested the hypothesis
      that (1) accelerated autophagy is a key contributor to VIDD; and that (2)
      oxidative stress is required to increase the expression of autophagy genes in the
      diaphragm. Our findings reveal that targeted inhibition of autophagy in the rat
      diaphragm prevented MV-induced muscle atrophy and contractile dysfunction.
      Attenuation of VIDD in these animals occurred as a result of increased diaphragm
      concentration of the antioxidant catalase and reduced mitochondrial ROS emission,
      which corresponded to reductions in the activity of calpain and caspase-3. To
      determine if increased ROS production is required for the upregulation of
      autophagy biomarkers in the diaphragm, rats that were administered the
      mitochondrial-targeted peptide SS-31 during MV. Results from this study
      demonstrated that mitochondrial ROS production in the diaphragm during MV is
      required for the increased expression of key autophagy genes (i.e. LC3, Atg7,
      Atg12, Beclin1 and p62), as well as for increased activity of cathepsin L.
      Together, these data reveal that autophagy is required for VIDD, and that
      autophagy inhibition reduces MV-induced diaphragm ROS production and prevents a
      positive feedback loop whereby increased autophagy is stimulated by oxidative
      stress, resulting in further increases in ROS and autophagy.

PMID- 29197634
TI  - Promoting the consumption of dairy products for fracture prevention: A good value
      for money?

PMID- 29197635
TI  - Temporary fixation of limbs and pelvis.
AB  - "Urgent, complete, definitive" treatment still today seems to be an appropriate
      attitude in many trauma cases. There are, however, several situations in which
      emergency definitive fixation is not the optimal strategy for all cases of
      fracture. Temporary fixation has a role to play in the orthopedic "trauma damage
      control" design comprising successive steps, as applied in multiple trauma,
      multiple fracture, severe multi-tissue limb lesions and soft-tissue lesions of
      unpredictable progression. The aim of this study is to define the strategies,
      indications, principles and limitations of temporary fixation in limb and pelvis
      fracture.

PMID- 29197636
TI  - Osteochondritis dissecans of the knee.
AB  - Osteochondritis dissecans (OCD) of the knee is an idiopathic, focal, subchondral
      bone abnormality that can cause instability or detachment of a bone fragment and
      overlying articular cartilage, with subsequent progression to osteoarthritis. The
      diagnosis is usually made during adolescence. Mechanical factors play a major
      role in the pathophysiology of OCD. When the radiographic diagnosis is made early
      in a patient with open physes, healing can often be obtained simply by
      restricting sports activities. The degree of lesion instability can be assessed
      by magnetic resonance imaging. When the lesion remains unstable and the pain
      persists despite a period of rest, surgery is indicated. Arthroscopic exploration
      is always the first step. Drilling of the lesion produces excellent outcomes if
      the lesion is stable. Unstable lesions require fixation and, in some cases, bone
      grafting. Defects must be filled, depending on their surface area. Although many
      surgical techniques are available, the therapeutic indications are now
      standardized.

PMID- 29197637
TI  - Intrathecal anti-suprabasin antibodies in SLE, a cause of local concern?

PMID- 29197638
TI  - Robust Transcriptional Activation in Plants Using Multiplexed CRISPR-Act2.0 and
      mTALE-Act Systems.
AB  - User-friendly tools for robust transcriptional activation of endogenous genes are
      highly demanded in plants. We previously showed that a dCas9-VP64 system
      consisting of the deactivated CRISPR-associated protein 9 (dCas9) fused with four
      tandem repeats of the transcriptional activator VP16 (VP64) could be used for
      transcriptional activation of endogenous genes in plants. In this study, we
      developed a second generation of vector systems for enhanced transcriptional
      activation in plants. We tested multiple strategies for dCas9-based
      transcriptional activation, and found that simultaneous recruitment of VP64 by
      dCas9 and a modified guide RNA scaffold gRNA2.0 (designated CRISPR-Act2.0)
      yielded stronger transcriptional activation than the dCas9-VP64 system. Moreover,
      we developed a multiplex transcription activator-like effector activation (mTALE
      Act) system for simultaneous activation of up to four genes in plants. Our
      results suggest that mTALE-Act is even more effective than CRISPR-Act2.0 in most
      cases tested. In addition, we explored tissue-specific gene activation using
      positive feedback loops. Interestingly, our study revealed that certain
      endogenous genes are more amenable than others to transcriptional activation, and
      tightly regulated genes may cause target gene silencing when perturbed by
      activation probes. Hence, these new tools could be used to investigate gene
      regulatory networks and their control mechanisms. Assembly of multiplex CRISPR
      Act2.0 and mTALE-Act systems are both based on streamlined and PCR-independent
      Golden Gate and Gateway cloning strategies, which will facilitate transcriptional
      activation applications in both dicots and monocots.

PMID- 29197639
TI  - A promising natural product, pristimerin, results in cytotoxicity against breast
      cancer stem cells in vitro and xenografts in vivo through apoptosis and an
      incomplete autopaghy in breast cancer.
AB  - Several natural products have been suggested as effective agents for the
      treatment of cancer. Given the important role of CSCs (Cancer Stem Cells) in
      cancer, which is a trendy hypothesis, it is worth investigating the effects of
      pristimerin on CSCs as well as on the other malignant cells (MCF-7 and MDA-MB
      231) of breast cancer. The anti-growth activity of pristimerin against MCF-7 and
      MCF-7s (cancer stem cell enriched population) cells was investigated by real time
      viability monitorization (xCELLigence System(r)) and ATP assay, respectively.
      Mode of cell death was evaluated using electron and fluorescence microscopies,
      western blotting (autophagy, apoptosis and ER-stress related markers) and flow
      cytometry (annexin-V staining, caspase 3/7 activity, BCL-2 and PI3K expressions).
      Pristimerin showed an anti-growth effect on cancer cells and cancer stem cells
      with IC50 values ranging at 0.38-1.75MUM. It inhibited sphere formation at
      relatively lower doses (<1.56MUM). Apoptosis was induced in MCF-7 and MCF-7s
      cells. In addition, extensive cytoplasmic vacuolation was observed, implying an
      incompleted autophagy as evidenced by the increase of autophagy-related proteins
      (p62 and LC3-II) with an unfolded protein response (UPR). Pristimerin inhibited
      the growth of MCF-7 and MDA-MB-231-originated xenografts in NOD.CB17-Prkdcscid/J
      mice. In mice, apoptosis was further confirmed by cleavage of PARP, activation of
      caspase 3 and/or 7 and TUNEL staining. Taken together, pristimerin shows
      cytotoxic activity on breast cancer both in vitro and in vivo. It seems to
      represent a robust promising agent for the treatment of breast cancer.
      Pristimerin's itself or synthetic novel derivatives should be taken into
      consideration for novel potent anticancer agent(s).

PMID- 29197640
TI  - Occurrence and profiles of halogenated phenols, polybrominated diphenyl ethers
      and hydroxylated polybrominated diphenyl ethers in the effluents of waste water
      treatment plants around Huang-Bo Sea, North China.
AB  - Halogenated organic pollutants (HOPs), as ubiquitous environment contaminants,
      have attracted increasing concerns due to the potential adverse health impacts on
      organisms and even humans. Waste water treatment plants (WWTPs) are one source of
      HOPs to the environment through their discharge of treated effluent. In this
      study, the presence and profiles of 6 halogenated phenols (HP), 17 polybrominated
      diphenyl ethers (PBDE) and 11 hydroxylated polybrominated diphenyl ethers (OH
      PBDE) were investigated in 12 WWTP effluent samples collected near Huang-Bo Sea
      in Dalian, China. These targeted organohalogen pollutants were found in all the
      effluent samples with the total concentrations of SigmaHPs, SigmaPBDEs and
      SigmaOH-PBDEs ranging from 77.2 to 168.5ng/L, from not-detected to 5.3ng/L and
      from 0.08 to 0.88ng/L, respectively. The most abundant congeners of HPs and PBDEs
      in the effluents were pentachlorophenol (PCP), BDE-47 and BDE-99, while for OH
      PBDEs, 6-OH-BDE-47 and 5-OH-BDE-47 were the most abundant. In addition, the
      statistical analysis showed that a significant (p<0.05) positive correlation was
      observed between BDE-47 and its metabolite 6-OH-BDE-47, indicating that PBDEs may
      be a source of OH-PBDEs detected in the effluents.

PMID- 29197641
TI  - Primary Care Providers' Use of a Child Psychiatry Telephone Support Program.
AB  - BACKGROUND: The Massachusetts Child Psychiatry Access Project (MCPAP) provides
      telephone support from mental health specialists to primary care providers
      (PCPs). Understanding PCPs' use may inform implementation of similar programs. We
      sought to examine PCPs' decision-making process to use or not use MCPAP when
      encountering mental health problems. METHODS: We analyzed data regarding calls
      from PCPs to MCPAP from October 1, 2010, to July 31, 2011, and interviewed 14
      PCPs with frequent use (>=7 calls) and infrequent use (<=4 calls). PCPs were
      asked about recent patients with mental health problems, and they were asked to
      describe reasons for calling or not calling MCPAP. Frequent callers were asked
      what sustained use; infrequent callers were asked about alternative management
      strategies. Comparisons were made between these groups in qualitative analysis.
      RESULTS: PCPs (n = 993) made 6526 calls (mean = 6.6; median = 3). Factors
      influencing calling included: MCPAP's guidance is timely and tailored to
      individual scope of practice; MCPAP's ability to arrange therapy referrals
      exceeds PCPs' ability; providing a plan at point of care relieves anxious
      families; and MCPAP's assistance helps accommodate families' preference to keep
      mental health in primary care. Some infrequent callers had gained skills through
      MCPAP before 2010 and now called only for complex cases. Other reasons for
      infrequent calling: PCPs have other consultation sources, have fear of being
      asked to manage more than they are comfortable, or have misperceptions of MCPAP's
      offerings. CONCLUSIONS: MCPAP enhanced PCPs' ability to deliver mental health
      care consistent with families' preferences. PCPs applied knowledge gained from
      calls to subsequent patients. Promoting MCPAP components through outreach and
      tailoring guidance to PCPs' scope of practice may entice greater use.

PMID- 29197642
TI  - Neuroimage special issue on brain segmentation and parcellation - Editorial.

PMID- 29197643
TI  - Anti-inflammatory meroterpenoids from the mangrove endophytic fungus Talaromyces
      amestolkiae YX1.
AB  - Four previously undescribed meroterpenoids, amestolkolides A-D, along with three
      known compounds were isolated from the mangrove endophytic fungus Talaromyces
      amestolkiae YX1 cultured on wheat solid-substrate medium culture. Their
      structures were elucidated by a combination of spectroscopic analyses. The
      absolute configurations of amestolkolides B and C, and purpurogenolide E were
      determined by single-crystal X-ray diffraction using Cu Kalpha radiation, and
      those of amestolkolides A and D were elucidated on the basis of experimental and
      calculated electronic circular dichroism spectra. The absolute configuration of
      amestolkolides A-D, and purpurogenolide E (9R) at C-9 was different from that of
      analogues (9S) in references, so that their plausible and distinct biosynthetic
      pathways were proposed. Amestolkolide B showed strong anti-inflammatory activity
      in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide
      activated in RAW264.7 cells with IC50 value of 1.6 +/- 0.1 MUM.

PMID- 29197644
TI  - Successful treatment of Rosai-Dorfman disease using ALA-PDT.
AB  - Rosai-Dorfman disease is a rare inflammatory cutaneous histiocytosis with the
      involvement of lymph nodes. Therapeutic interventions include thalidomide,
      corticosteroids, surgical excision and radiotherapy . In this article, we report
      a case that was successfully treated with ALA photodynamic therapy.

PMID- 29197645
TI  - The impact of iatrogenic glottic atresia due to photodynamic therapy for
      laryngeal cancer: A report of two cases.
AB  - Photodynamic therapy (PDT) is a minimally invasive therapy used in the treatment
      of premalignant and malignant diseases, including head and neck carcinomas. It
      can be applied before or after chemotherapy, irradiation, or surgery. Unlike
      irradiation and surgery, it can be repeated many times at the same site, and it
      is also associated with better cosmetic and functional outcomes [1]. We have
      treated 10 patients with laryngeal carcinomas with PDT since 1998, and herein we
      describe two such patients who developed vocal cord adhesion due to PDT. To our
      knowledge, there are no previous reports of patients with glottis atresia due to
      PDT, thus the cases reported herein are rare, and educationally valuable.

PMID- 29197646
TI  - One-stage and two-stage meta-analysis of individual participant data led to
      consistent summarized evidence: lessons learned from combining multiple
      databases.
AB  - OBJECTIVE: Combining multiple health-care databases (DBs) allows comparing the
      effects of a wide variety of health-care services. There is a growing interest in
      methods for combining the results from multiple DBs. We attempted to learn
      lessons about the performance of one- and two-stage approaches from the
      reanalysis of data drawn from two studies of pharmacoepidemiology based on
      multiple DBs. STUDY DESIGN AND SETTING: Two nested case-control studies were
      carried out for estimating the tricyclic antidepressants (TCAs)-arrhythmia and
      etoricoxib-heart failure associations, respectively, from the Italian Group for
      Appropriate Drug Prescription in the Elderly and the European Safety of Non
      Steroidal Anti-Inflammatory programs. The associations of interest were modeled
      by conditional logistic regression for matched case-control sets, fitting fixed
      effect and random-effect models with both one- and two-stage approaches. RESULTS:
      One- and two-stage approaches gave very similar results, showing uncertainty of
      TCA-arrhythmia association (random-effect odds ratios [ORs], 95% confidence
      interval [CI], 1.26, 0.71-2.24, and 1.30, 0.66-2.55, respectively) and
      statistical evidence for etoricoxib-heart failure association (fixed-effect OR,
      95% CI, 1.53, 1.41-1.66, and 1.54, 1.42-1.66, respectively). CONCLUSION: Our
      study offers further evidence that two-stage approach generates estimates very
      similar as those from one-stage approach, even in the case of between-DB exposure
      heterogeneity and when several covariates must be concurrently considered. As
      current rules limit the free movement of electronic health data, our findings
      open the door of treating data within the country where they are generated and
      then to apply conventional techniques for summarizing estimates, which is the two
      stage approach for meta-analysis using individual participant data.

PMID- 29197647
TI  - Genetic basis of chromosomally-encoded mcr-1 gene.
AB  - Compared with plasmid-borne mcr-1, the occurrence of chromosomally-encoded mcr-1
      is rare although it has been reported in several cases. This study aimed to
      investigate the genetic features of chromosomally-encoded mcr-1 among Escherichia
      coli strains as well as the potential genetic basis governing mobilisation of mcr
      1 in bacterial chromosomes. The genome sequences of 16 E. coli strains containing
      a chromosomal mcr-1 gene were obtained and analysed. Phylogenetic and whole
      genome sequencing (WGS) analysis demonstrated that mcr-1 was associated with four
      major types of genetic arrangements, namely ISApl1-mcr1-orf, Tn6330, complex
      Tn6330 and DeltaTn6330 in chromosomes of genetically unrelated E. coli strains.
      The mcr-1-carrying mobile elements were shown to insert into the AT-rich region,
      which was also the case for ISApl1. Analysis of complete E. coli genome sequences
      showed that there were multiple copies of ISApl1 present in E. coli chromosomes
      that also carried mcr-1, whilst all mcr-1-negative chromosomes were absent of any
      copy of ISApl1, suggesting the strong association of ISApl1 and mcr-1. Insertion
      of ISApl1 into E. coli chromosomes may be a prerequisite for the insertion of mcr
      1-carrying mobile elements. Insertion of mcr-1 into E. coli chromosomes would
      enable it to become intrinsically resistant, which is expected to become more
      prevalent. Policy on the prudent use of colistin both in veterinary and clinical
      settings should be imposed globally to further prevent dissemination of mcr-1 in
      E. coli and other bacterial pathogens.

PMID- 29197648
TI  - Elevated antimicrobial residues in animal food products call for institutional
      changes on veterinary drug management and animal food product surveillance in
      China.

PMID- 29197650
TI  - KCC2, epileptiform synchronization, and epileptic disorders.
AB  - The K+-Cl- co-transporter KCC2 is a neuron-specific, Cl- extruder that uses K+
      gradient for maintaining low intracellular [Cl-]. It is indeed well established
      that sustaining an outwardly-directed electrochemical Cl- gradient across the
      neuronal membrane is fundamental for a proper function of postsynaptic GABAA
      receptor signaling. In particular, studies in the last two decades have shown
      that KCC2 activity is important to maintain a hyperpolarizing GABAergic
      neurotransmission. Conversely, low KCC2 activity should lead to depolarizing, and
      under specific conditions, excitatory GABAergic transmission. Not surprisingly
      given the critical role of KCC2 in regulating the inhibitory drive, alterations
      in its expression levels and activity are linked with epilepsy. Here, we will
      first summarize data regarding the role of KCC2 in epileptiform synchronization.
      Next, we will review evidence indicating that KCC2 expression and function are
      altered in chronic epileptic disorders, both in the developing and adult brain.
      We will also go through recent findings regarding the molecular mechanisms
      underlying the changes in KCC2 activity that occur following seizures. Finally,
      we will consider the modulation of KCC2 function as a potential, novel
      therapeutic target for the treatment of epileptic disorders.

PMID- 29197649
TI  - Heritable genotype contrast mining reveals novel gene associations specific to
      autism subgroups.
AB  - Though the genetic etiology of autism is complex, our understanding can be
      improved by identifying genes and gene-gene interactions that contribute to the
      development of specific autism subtypes. Identifying such gene groupings will
      allow individuals to be diagnosed and treated according to their precise
      characteristics. To this end, we developed a method to associate gene
      combinations with groups with shared autism traits, targeting genetic elements
      that distinguish patient populations with opposing phenotypes. Our computational
      method prioritizes genetic variants for genome-wide association, then utilizes
      Frequent Pattern Mining to highlight potential interactions between variants. We
      introduce a novel genotype assessment metric, the Unique Inherited Combination
      support, which accounts for inheritance patterns observed in the nuclear family
      while estimating the impact of genetic variation on phenotype manifestation at
      the individual level. High-contrast variant combinations are tested for
      significant subgroup associations. We apply this method by contrasting autism
      subgroups defined by severe or mild manifestations of a phenotype. Significant
      associations connected 286 genes to the subgroups, including 193 novel autism
      candidates. 71 pairs of genes have joint associations with subgroups, presenting
      opportunities to investigate interacting functions. This study analyzed 12 autism
      subgroups, but our informatics method can explore other meaningful divisions of
      autism patients, and can further be applied to reveal precise genetic
      associations within other phenotypically heterogeneous disorders, such as
      Alzheimer's disease.

PMID- 29197651
TI  - Yawning-Its anatomy, chemistry, role, and pathological considerations.
AB  - Yawning is a clinical sign of the activity of various supra- and infratentorial
      brain regions including the putative brainstem motor pattern, hypothalamic
      paraventricular nucleus, probably the insula and limbic structures that are
      interconnected via a fiber network. This interaction can be seen in analogy to
      other cerebral functions arising from a network or zone such as language. Within
      this network, yawning fulfills its function in a stereotype, reflex-like manner;
      a phylogenetically old function, preserved across species barriers, with the
      purpose of arousal, communication, and maybe other functions including
      respiration. Abnormal yawning with >=3 yawns/15min without obvious cause arises
      from lesions of brain areas involved in the yawning zone, its trajectories
      causing a disconnection syndrome, or from alteration of network activity by
      physical or metabolic etiologies including medication.

PMID- 29197652
TI  - Crustacean olfactory systems: A comparative review and a crustacean perspective
      on olfaction in insects.
AB  - Malacostracan crustaceans display a large diversity of sizes, morphs and life
      styles. However, only a few representatives of decapod taxa have served as models
      for analyzing crustacean olfaction, such as crayfish and spiny lobsters.
      Crustaceans bear multiple parallel chemosensory pathways represented by different
      populations of unimodal chemosensory and bimodal chemo- and mechanosensory
      sensilla on the mouthparts, the walking limbs and primarily on their two pairs of
      antennae. Here, we focus on the olfactory pathway associated with the unimodal
      chemosensory sensilla on the first antennal pair, the aesthetascs. We explore the
      diverse arrangement of these sensilla across malacostracan taxa and point out
      evolutionary transformations which occurred in the central olfactory pathway. We
      discuss the evolution of chemoreceptor proteins, comparative aspects of active
      chemoreception and the temporal resolution of crustacean olfactory system.
      Viewing the evolution of crustacean brains in light of energetic constraints can
      help us understand their functional morphology and suggests that in various
      crustacean lineages, the brains were simplified convergently because of metabolic
      limitations. Comparing the wiring of afferents, interneurons and output neurons
      within the olfactory glomeruli suggests a deep homology of insect and crustacean
      olfactory systems. However, both taxa followed distinct lineages during the
      evolutionary elaboration of their olfactory systems. A comparison with insects
      suggests their olfactory systems o especially that of the vinegar fly o to be
      superb examples for "economy of design". Such a comparison also inspires new
      thoughts about olfactory coding and the functioning of malacostracan olfactory
      systems in general.

PMID- 29197653
TI  - Ectopic pregnancy 6 years after subtotal hysterectomy: A case report.
AB  - BACKGROUND: Only 57 cases of ectopic pregnancy after hysterectomy have been
      published. CASE REPORT: A 34-year-old patient with a history of subtotal
      hysterectomy for postpartum hemorrhage consulted for acute abdominal pain. The
      diagnosis of ectopic pregnancy was made using blood pregnancy test and
      transvaginal ultrasound. Emergency laparoscopy was performed. CONCLUSION: Urine
      pregnancy test should be performed in case of unexplained haemoperitoneum in
      patient of childbearing age with a history of hysterectomy. Fistulous tracts
      between the patent cervix or the vaginal cuff and the peritoneal cavity may allow
      fecundation. TEACHING POINTS: (1) Ectopic pregnancy remains a differential
      diagnosis of abdominal pain and haemoperitoneum in patient of childbearing age
      even after hysterectomy. (2) Fistulous tract between the residual cervix and the
      peritoneal cavity or tubes may allow fecundation.

PMID- 29197654
TI  - Exploring viral reservoir: The combining approach of cell sorting and droplet
      digital PCR.
AB  - Combined antiretroviral therapy (cART) blocks different steps of HIV replication
      and maintains plasma viral RNA at undetectable levels. The virus can remain in
      long-living cells and create a reservoir where HIV can restart replicating after
      cART discontinuation. A persistent viral production triggers and maintains a
      persistent immune activation, which is a well-known feature of chronic HIV
      infection, and contributes either to precocious aging, or to the increased
      incidence of morbidity and mortality of HIV positive patients. The new frontier
      of the treatment of HIV infection is nowadays eradication of the virus from all
      host cells and tissues. For this reason, it is crucial to have a clear and
      precise idea of where the virus hides, and which are the cells that keep it
      silent. Important efforts have been made to improve the detection of viral
      reservoirs, and new techniques are now giving the opportunity to characterize
      viral reservoirs. Among these techniques, a strategic approach based upon cell
      sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities
      of research. This review provides an overview of the methods that combine cell
      sorting and ddPCR for the quantification of HIV DNA in different cell types, and
      for the detection of its maintenance.

PMID- 29197655
TI  - Multiplexed approaches correlating mitochondrial health to cell health using
      microcapillary cytometry.
AB  - Mitochondria are critical cellular organelles that play a fundamental role in
      cellular metabolism and oxidative stress and are well known to trigger multiple
      cell death pathways. The study of sequence of mitochondrial events as it relates
      to apoptotic/cell death events can provide critical insights into mechanism of
      cellular homeostasis, stress and death. Availability of rapid and simplified
      cytometric testing methods for evaluating mitochondrial changes, apoptosis and
      cell death in parallel can greatly enhance our understanding of mechanism of
      compound action. In this study, we investigated a series of compounds to evaluate
      apoptotic/cell death effects in context of mitochondrial changes using plate
      based assays on Guava(r) easyCyte systems. Studies utilized multiplexed assays
      for mitochondrial membrane potential changes and apoptosis/cell death markers and
      allowed for easy identification of hit compounds. Dose and time response studies
      with Niclosamide, an anti-helmintic drug and comparison of effects with Gambogic
      acid and celastrol demonstrated early and significant mitochondrial impacts for
      niclosamide and gambogic acid. No apoptotic or cell death impacts were observed
      in parallel at low doses/short times of incubation for niclosamide, while
      increased time with niclosamide caused increase in mitochondrial, apoptotic and
      cell death response. The method demonstrates great power in being able to
      distinguish between potency of compounds and conditions in modulating
      mitochondrial/apoptotic changes. The simplicity of the assays described coupled
      with the ease of use of plate based microcapillary cytometry can provide
      researchers valuable tools to obtain a more comprehensive insight into how
      compounds modulate mitochondria and its relationship with subsequent
      apoptosis/cell death pathways.

PMID- 29197656
TI  - Endocardial infarct scar recognition by myocardial electrical impedance is not
      influenced by changes in cardiac activation sequence.
AB  - BACKGROUND: Measurement of myocardial electrical impedance can allow recognition
      of infarct scar and is theoretically not influenced by changes in cardiac
      activation sequence, but this is not known. OBJECTIVES: The objectives of this
      study were to evaluate the ability of endocardial electrical impedance
      measurements to recognize areas of infarct scar and to assess the stability of
      the impedance data under changes in cardiac activation sequence. METHODS: One
      month-old myocardial infarction confirmed by cardiac magnetic resonance imaging
      was induced in 5 pigs submitted to coronary artery catheter balloon occlusion.
      Electroanatomic data and local electrical impedance (magnitude, phase angle, and
      amplitude of the systolic-diastolic impedance curve) were recorded at multiple
      endocardial sites in sinus rhythm and during right ventricular pacing. By merging
      the cardiac magnetic resonance and electroanatomic data, we classified each
      impedance measurement site either as healthy (bipolar amplitude >=1.5 mV and
      maximum pixel intensity <40%) or scar (bipolar amplitude <1.5 mV and maximum
      pixel intensity >=40%). RESULTS: A total of 137 endocardial sites were studied.
      Compared to healthy tissue, areas of infarct scar showed 37.4% reduction in
      impedance magnitude (P < .001) and 21.5% decrease in phase angle (P < .001). The
      best predictive ability to detect infarct scar was achieved by the combination of
      the 4 impedance parameters (area under the receiver operating characteristic
      curve 0.96; 95% confidence interval 0.92-1.00). In contrast to voltage mapping,
      right ventricular pacing did not significantly modify the impedance data.
      CONCLUSION: Endocardial catheter measurement of electrical impedance can identify
      infarct scar regions, and in contrast to voltage mapping, the impedance data are
      not affected by changes in cardiac activation sequence.

PMID- 29197657
TI  - Feasibility of extravascular pacing with a novel substernal electrode
      configuration: The Substernal Pacing Acute Clinical Evaluation study.
AB  - BACKGROUND: Subcutaneous implantable cardioverter-defibrillators provide an
      alternative to transvenous defibrillation but require higher shock outputs and
      offer no antitachycardia pacing. The Substernal Pacing Acute Clinical Evaluation
      (SPACE) study evaluated the feasibility of pacing from an extravascular
      substernal location. OBJECTIVES: The primary purpose of the SPACE study was to
      characterize pacing from the substernal space. Secondary objectives included
      evaluating extracardiac stimulation and recording electrograms. METHODS: The
      SPACE study prospectively evaluated the feasibility of pacing with a commercially
      available electrophysiology catheter acutely implanted in the substernal space
      via minimally invasive subxiphoid access. Pacing data were collected in >=7
      vectors using constant current stimulation up to 20 mA and pulse width up to 10
      ms. RESULTS: Catheter placement was successful in all 26 patients who underwent
      the procedure, with a mean placement time of 11.7 +/- 10.1 minutes. Eighteen
      patients (69%) had successful ventricular capture in >=1 tested vector. The mean
      pacing threshold at a pulse width of 10 ms was 7.3 +/- 4.2 mA across all vectors
      (5.8 +/- 4.4 V). Failed capture was generally associated with suboptimal catheter
      placement or presumed air ingression. A low level of extracardiac stimulation was
      observed in 1 patient. The mean R-wave amplitude ranged from 2.98 to 4.11 mV in
      the unipolar configuration and from 0.83 to 3.95 mV in the bipolar configuration.
      CONCLUSION: The data from the SPACE study demonstrate that pacing is feasible
      from the extravascular substernal location. A substernal electrode configuration
      has the potential to provide pacing in a future extravascular device without need
      for intracardiac hardware placement.

PMID- 29197658
TI  - Using the genome aggregation database, computational pathogenicity prediction
      tools, and patch clamp heterologous expression studies to demote previously
      published long QT syndrome type 1 mutations from pathogenic to benign.
AB  - BACKGROUND: Mutations in the KCNQ1-encoded Kv7.1 potassium channel cause long QT
      syndrome (LQTS) type 1 (LQT1). It has been suggested that ~10%-20% of rare LQTS
      case-derived variants in the literature may have been published erroneously as
      LQT1-causative mutations and may be "false positives." OBJECTIVE: The purpose of
      this study was to determine which previously published KCNQ1 case variants are
      likely false positives. METHODS: A list of all published, case-derived KCNQ1
      missense variants (MVs) was compiled. The occurrence of each MV within the Genome
      Aggregation Database (gnomAD) was assessed. Eight in silico tools were used to
      predict each variant's pathogenicity. Case-derived variants that were either (1)
      too frequently found in gnomAD or (2) absent in gnomAD but predicted to be
      pathogenic by <=2 tools were considered potential false positives. Three of these
      variants were characterized functionally using whole-cell patch clamp technique.
      RESULTS: Overall, there were 244 KCNQ1 case-derived MVs. Of these, 29 (12%) were
      seen in >=10 individuals in gnomAD and are demotable. However, 157 of 244 MVs
      (64%) were absent in gnomAD. Of these, 7 (4%) were predicted to be pathogenic by
      <=2 tools, 3 of which we characterized functionally. There was no significant
      difference in current density between heterozygous KCNQ1-F127L, -P477L, or -L619M
      variant-containing channels compared to KCNQ1-WT. CONCLUSION: This study offers
      preliminary evidence for the demotion of 32 (13%) previously published LQT1 MVs.
      Of these, 29 were demoted because of their frequent sighting in gnomAD.
      Additionally, in silico analysis and in vitro functional studies have facilitated
      the demotion of 3 ultra-rare MVs (F127L, P477L, L619M).

PMID- 29197659
TI  - Network-based method for mining novel HPV infection related genes using random
      walk with restart algorithm.
AB  - The human papillomavirus (HPV), a common virus that infects the reproductive
      tract, may lead to malignant changes within the infection area in certain cases
      and is directly associated with such cancers as cervical cancer, anal cancer, and
      vaginal cancer. Identification of novel HPV infection related genes can lead to a
      better understanding of the specific signal pathways and cellular processes
      related to HPV infection, providing information for the development of more
      efficient therapies. In this study, several novel HPV infection related genes
      were predicted by a computation method based on the known genes involved in HPV
      infection from HPVbase. This method applied the algorithm of random walk with
      restart (RWR) to a protein-protein interaction (PPI) network. The candidate genes
      were further filtered by the permutation and association tests. These steps
      eliminated genes occupying special positions in the PPI network and selected key
      genes with strong associations to known HPV infection related genes based on the
      interaction confidence and functional similarity obtained from published
      databases, such as STRING, gene ontology (GO) terms and KEGG pathways. Our study
      identified 104 novel HPV infection related genes, a number of which were
      confirmed to relate to the infection processes and complications of HPV
      infection, as reported in the literature. These results demonstrate the
      reliability of our method in identifying HPV infection related genes. This
      article is part of a Special Issue entitled: Accelerating Precision Medicine
      through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.

PMID- 29197661
TI  - Functional assessment of hepatobiliary secretion by 11C-cholylsarcosine positron
      emission tomography.
AB  - Positron emission tomography (PET) with 11C-cholylsarcosine (11C-CSar), a
      radiolabelled synthetic N-methylglycine (sarcosine) conjugate of cholic acid, is
      a novel molecular imaging technique that enables quantitative assessment of the
      individual transport steps involved in hepatic secretion of conjugated bile
      acids. Here, we present the method and discuss its potential clinical and
      scientific applications based on findings in the first human study of healthy
      subjects and patients with cholestasis. We also present a clinical example of a
      patient studied during and six months after an episode of drug-induced
      cholestatic liver injury.

PMID- 29197660
TI  - Metabolomic markers of fatigue: Association between circulating metabolome and
      fatigue in women with chronic widespread pain.
AB  - BACKGROUND: Fatigue is a sensation of unbearable tiredness that frequently
      accompanies chronic widespread musculoskeletal pain (CWP) and inflammatory joint
      disease. Its mechanisms are poorly understood and there is a lack of effective
      biomarkers for diagnosis and onset prediction. We studied the circulating
      metabolome in a population sample characterised for CWP to identify biomarkers
      showing specificity for fatigue. MATERIAL AND METHODS: Untargeted metabolomic
      profiling was conducted on fasting plasma and serum samples of 1106 females with
      and without CWP from the TwinsUK cohort. Linear mixed-effects models accounting
      for covariates were used to determine relationships between fatigue and
      metabolites. Receiver operating curve (ROC)-analysis was used to determine
      predictive value of metabolites for fatigue. RESULTS: While no association
      between fatigue and metabolites was identified in twins without CWP (n=711), in
      participants with CWP (n=395), levels of eicosapentaenoate (EPA) omega-3 fatty
      acid were significantly reduced in those with fatigue (beta=-0.452+/-0.116;
      p=1.2*10-4). A significant association between fatigue and two other metabolites
      also emerged when BMI was excluded from the model: 3-carboxy-4-methyl-5-propyl-2
      furanpropanoate (CMPF), and C-glycosyltryptophan (p=1.5*10-4 and p=3.1*10-4,
      respectively). ROC analysis has identified a combination of 15 circulating
      metabolites with good predictive potential for fatigue in CWP (AUC=75%; 95% CI 69
      80%). CONCLUSION: The results of this agnostic metabolomics screening show that
      fatigue is metabolically distinct from CWP, and is associated with a decrease in
      circulating levels of EPA. Our panel of circulating metabolites provides the
      starting point for a diagnostic test for fatigue in CWP.

PMID- 29197662
TI  - New perspectives for pharmacological chaperoning treatment in methylmalonic
      aciduria cblB type.

PMID- 29197663
TI  - Prediction of potential drivers connecting different dysfunctional levels in lung
      adenocarcinoma via a protein-protein interaction network.
AB  - Lung cancer is a serious disease that threatens an affected individual's life.
      Its pathogenesis has not yet to be fully described, thereby impeding the
      development of effective treatments and preventive measures. "Cancer driver"
      theory considers that tumor initiation can be associated with a number of
      specific mutations in genes called cancer driver genes. Four omics levels,
      namely, (1) methylation, (2) microRNA, (3) mutation, and (4) mRNA levels, are
      utilized to cluster cancer driver genes. In this study, the known dysfunctional
      genes of these four levels were used to identify novel driver genes of lung
      adenocarcinoma, a subtype of lung cancer. These genes could contribute to the
      initiation and progression of lung adenocarcinoma in at least two levels. First,
      random walk with restart algorithm was performed on a protein-protein interaction
      (PPI) network constructed with PPI information in STRING by using known
      dysfunctional genes as seed nodes for each level, thereby yielding four groups of
      possible genes. Second, these genes were further evaluated in a test strategy to
      exclude false positives and select the most important ones. Finally, after
      conducting an intersection operation in any two groups of genes, we obtained
      several inferred driver genes that contributed to the initiation of lung
      adenocarcinoma in at least two omics levels. Several genes from these groups
      could be confirmed according to recently published studies. The inferred genes
      reported in this study were also different from those described in a previous
      study, suggesting that they can be used as essential supplementary data for
      investigations on the initiation of lung adenocarcinoma. This article is part of
      a Special Issue entitled: Accelerating Precision Medicine through Genetic and
      Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.

PMID- 29197664
TI  - Emerging metabolic risk factors in hepatocellular carcinoma and their influence
      on the liver microenvironment.
AB  - Despite the reducing incidence of chronic hepatitis infections, an unexpected
      increasing incidence of hepatocellular carcinoma (HCC) has being occurred. This
      may be explained by the increasing number of HCCs developing on steatosis (NAFLD)
      and steatohepatitis (NASH), related to metabolic risk factors (i.e. diabetes
      mellitus type II, obesity, metabolic syndrome), which are becoming emerging risk
      factors for HCC. This led to a growing scientific interest on the oncogenic
      mechanisms underlying the transition from NAFLD to HCC. However, patients with
      NASH receive significantly less HCC surveillance than patients with chronic
      hepatitis, and no specific preventive pharmacological treatments have recommended
      for NASH-related HCC. This review focuses on the pathogenic role of the emerging
      factors involved in the transition from NAFLD/NASH to HCC, including microbiota,
      insulin resistance, inflammation, lipid and bile acids metabolism. It will be
      emphasize their impact on the liver microenvironment, the implications in
      clinical practice and the future directions of research.

PMID- 29197665
TI  - To create or to recall original ideas: Brain processes associated with the
      imagination of novel object uses.
AB  - This fMRI study investigated what brain processes contribute to the generation of
      new ideas. Brain activation was measured while participants generated new
      original object uses, recalled original object uses, or recalled common object
      uses. Post-scan evaluations were used to confirm what ideas were newly generated
      on the spot or actually retrieved from memory. When compared to the recall of
      common ideas, the generation of new and old original ideas showed a similar
      activation pattern including activation of bilateral parahippocampal and mPFC
      regions, suggesting that the construction of new ideas builds on similar
      processes like the reconstruction of original ideas from episodic memory. As a
      difference, the generation of new object uses involved higher activation of a
      focused cluster in the left supramarginal gyrus compared to the recall of
      original ideas. This finding adds to the converging evidence that the left
      supramarginal gyrus is crucially involved in the construction of novel
      representations, potentially by integrating memory content in new ways and
      supporting executively demanding mental simulations. This study deepens our
      understanding of how creative thought builds on and goes beyond memory.

PMID- 29197666
TI  - Surgical outcome and predictive factors of epilepsy surgery in pediatric isolated
      focal cortical dysplasia.
AB  - OBJECTIVE: Focal cortical dysplasia (FCD) is a common cause of medically
      intractable epilepsy in children. Epilepsy surgery has been a valuable treatment
      option to achieve seizure freedom in these intractable epilepsy patients. We
      aimed to present long-term surgical outcome, in relation to pathological
      severity, and to assess predictive factors of epilepsy surgery in pediatric
      isolated FCD. METHODS: We retrospectively analyzed the data of 58 children and
      adolescents, with FCD International League Against Epilepsy (ILAE) task force
      classification types I and II, who underwent resective epilepsy surgery and were
      followed for at least 2 years after surgery. RESULTS: The mean age at epilepsy
      onset was 4.3 years (0-14.2 years), and mean age at epilepsy surgery was 9.4
      years (0.4-17.5 years). The mean duration of postoperative follow-up was 5.1+/
      2.6 years (2-12.4 years). Of 58 patients, 62% of patients achieved Engel class I
      at 2 years postoperatively, 58% at 5 years postoperatively, and 53% at the last
      follow up. Forty eight percent of our cohort successfully discontinued
      antiepileptic medication. Of 30 patients with seizure recurrence, 83% of seizures
      recurred within 2 years after surgery. We observed that FCD type IIb was
      significantly associated with a better surgical outcome. At fifth postoperative
      year, 88% of FCD IIb patients were seizure free compared with 21% of type I and
      57% of type IIa patients (P=0.043). By multivariate analysis, lesion on MRI
      (P=0.02) and complete resection (P<0.01) were the most important predictive
      factors for a seizure-free outcome. SIGNIFICANCE: Epilepsy surgery is highly
      effective; more than half of medically intractable epilepsy patients achieved
      seizure freedom after surgery. In addition, we found significant difference in
      surgical outcomes according to the ILAE task force classification. Lesion on MRI
      and complete resection were the most important predictive factors for favorable
      seizure outcome in isolated FCD patients.

PMID- 29197667
TI  - Indirect comparison of third-generation antiepileptic drugs as adjunctive
      treatment for uncontrolled focal epilepsy.
AB  - PURPOSE: Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and
      Brivaracetam (BRV), have recently been marketed as third-generation antiepileptic
      drugs (AEDs). We conducted a meta-analysis to indirectly compare overall efficacy
      and tolerability between third-generation AEDs in uncontrolled focal epilepsy.
      METHODS: We performed an online database search using Pubmed, Embase, Cochrane
      Online Library, and Clinicaltrial.gov for all available randomized controlled
      trials (RCTs) that investigated the therapeutic effects over a range of AED doses
      versus placebo. We then compared clinical efficacy and tolerability between these
      newer AEDs using Indirect Treatment Comparison software. RESULTS: Nineteen RCTs
      with a total of 7245 patients were included in our study. There were no
      significant differences in the risk difference of 50% responder rates and seizure
      free rates between third generation AEDs, regardless of dose. The risk of
      treatment emergent adverse events was significantly higher with ESL and PER
      treatment compared to BRV at all doses combined. Withdrawal rates due to adverse
      events were also significantly higher in patients treated with the highest doses
      of LAC and PER versus BRV, while treatment with ESL or LAC was related to higher
      withdrawal rates versus BRV when all doses were combined. CONCLUSIONS: Our
      analysis suggested there were no significant differences in efficacy between
      third generation AEDs in uncontrolled focal epilepsy. BRV may have the best
      tolerability profile. The other AEDs were associated with a higher risk for
      intolerable adverse, especially when taken at a high doses. The results from
      these indirect comparisons warrant further examination and verification through
      future well-designed trials.

PMID- 29197668
TI  - The new definition and classification of seizures and epilepsy.
AB  - This review discusses the updated classifications of seizures and the epilepsies,
      which were recently published by the International League Against Epilepsy
      (ILAE). While it is always a challenge to learn a new classification system,
      particularly one that has remained essentially unchanged for over three decades,
      these new classifications allow for the inclusion of some previously
      unclassifiable seizure types and utilize more intuitive terminology. In this
      review, we specifically discuss the use of these new classifications for
      patients, clinicians, and researchers.

PMID- 29197669
TI  - Vitamin D deficiency in children with epilepsy taking valproate and levetiracetam
      as monotherapy.
AB  - OBJECTIVE: The aim of this study is to evaluate if valproate (VPA) and
      levetiracetam (LEV) as monotherapy are associated with vitamin D deficiency among
      children with epilepsy. MATERIAL & METHODS: A cross-sectional clinical (seizure
      types, aetiology of epilepsy, dosage, drug levels, and duration of AED treatment)
      and blood testing (calcium, phosphorus, 25-OHD and PTH) study was accomplished in
      90 epileptic children (AED group: 59 receiving VPA, and 31 receiving LEV) and a
      control group (244 healthy subjects). 25-OHD levels were categorized as low
      (<20ng/ml), borderline (20-29ng/ml), or normal (>30ng/ml) RESULTS: The average
      dosage of VPA and LEV was 20.7+/-4.7mg/kg/d and 24.1+/-7.9mg/kg/d, respectively.
      The mean duration of VPA therapy was 2.5+/-1.4years, and with LEV was 2.3+/
      1.6years. Mean calcium and 25-OHD levels were significantly higher (p <0.05) in
      the control group. There was a negative correlation (p <0.01) between 25-OHD and
      VPA levels (r=-0.442). Vitamin D deficiency (%) was significantly higher (p
      <0.05) in VPA (24.1%) and LEV (35.5%) groups than in control group (14%). The
      multiple logistic regression analysis showed that VPA monotherapy (OR: 1.9, CI
      95%: 1.1-3.8) and LEV monotherapy (OR: 3.3, CI 95%: 1.5-7.5) were associated with
      an increased risk of vitamin D deficiency. CONCLUSIONS: The prevalence of vitamin
      D deficiency is common in children with epilepsy taking VPA or LEV. Hence vitamin
      D status of children treated with VPA and LEV should be regularly monitored and
      vitamin D supplements should be considered on an individual basis.

PMID- 29197670
TI  - Can POPs be substantially popped out through sweat?

PMID- 29197671
TI  - The in vitro renal cell toxicity of some unconventional anticancer phenanthroline
      based platinum(II) complexes.
AB  - The cytotoxicity of platinum(II) complexes coordinated to a chiral diamine, 1S,2S
      diaminocyclohexane or 1R,2R-diaminocyclohexane and 1,10-phenanthroline or 3,4,7,8
      tetramethyl-1,10-phenanthroline has been investigated in the renal proximal
      tubule HK-2 cell line. All platinum(II) complexes exhibited lower cytotoxicity in
      HK-2 cells (IC50 1.7-25MUM) than in A2780 ovarian cancer cells or cisplatin
      resistant A2780cisR cells (IC50 0.2-2.1MUM) (at 48h). PHENSS ([Pt(1,10
      phenanthroline)(1S,2S-dach)]2+) induced apoptosis and necrosis in ovarian cancer
      cells at concentrations that are relatively cytostatic to renal cells. Cisplatin
      was similarly or more cytotoxic to renal cells than ovarian cancer cells. Similar
      trends were reflected with shorter term exposure (1.5h). PHENSS demonstrated a
      comparatively cytostatic mode of action in renal cell cultures than cisplatin, as
      demonstrated by lower toxicity at higher concentrations (90MUM). PHENSS induced
      an elongated renal cell morphology, cytoskeletal stress fibre thickening, and
      increased beta-galactosidase activity, but no detectable change in reactive
      oxygen species generation or cell cycle distribution. In contrast, cisplatin
      treatment was associated with increased oxidative stress, cellular enlargement,
      G2/M arrest and apoptosis. The cytotoxicity of all platinum(II) complexes in both
      renal and ovarian cell lines were reduced in the presence of organic cation
      transporter (OCT) inhibitors cimetidine, disopyramide and amantadine. PHENSS and
      analogues demonstrated low level genotoxicity in an in vitro micronuclei assay
      compared to cisplatin or etoposide. These findings highlight PHENSS and other
      phen-based unconventional platinum(II) complexes as promising anticancer agents
      with alternative modes of action that induce lower kidney cell toxicity and
      genotoxicity, while demonstrating greater cisplatin-resistant ovarian cancer cell
      toxicity.

PMID- 29197672
TI  - Visualizing bacterial DNA replication and repair with molecular resolution.
AB  - Although DNA replication and repair in bacteria have been extensively studied for
      many decades, in recent years the development of single-molecule microscopy has
      provided a new perspective on these fundamental processes. Because single
      molecule imaging super-resolves the nanometer-scale dynamics of molecules, and
      because single-molecule imaging is sensitive to heterogeneities within a sample,
      this nanoscopic microscopy technique measures the motions, localizations, and
      interactions of proteins in real time without averaging ensemble observations,
      both in vitro and in vivo. In this Review, we provide an overview of several
      recent single-molecule fluorescence microscopy studies on DNA replication and
      repair. These experiments have shown that, in both Escherichia coli and Bacillus
      subtilis the DNA replication proteins are highly dynamic. In particular, even
      highly processive replicative DNA polymerases exchange to and from the
      replication fork on the scale of a few seconds. Furthermore, single-molecule
      investigations of the DNA mismatch repair (MMR) pathway have measured the complex
      interactions between MMR proteins, replication proteins, and DNA. Single-molecule
      imaging will continue to improve our understanding of fundamental processes in
      bacteria including DNA replication and repair.

PMID- 29197673
TI  - After the deluge: mining Staphylococcus aureus genomic data for clinical
      associations and host-pathogen interactions.
AB  - The genome of Staphylococcus aureus has rapidly become one the most frequently
      sequenced among bacteria, with more than 40000 genome sequences uploaded to
      public databases. Computational resources required for analysis and quality
      assessment have lagged behind accumulation of sequence data. Improved analytic
      pipelines, in combination with the development of customized S. aureus reference
      databases, can be used to inform S. aureus biology and potentially predict
      clinical outcome. Here, we review the currently available data about S. aureus
      genome in public databases, and discuss their potential utility for understanding
      S. aureus evolution. Also discussed are ways to overcome challenges to the
      application of whole-genome sequencing data for prevention and management of S.
      aureus disease.

PMID- 29197674
TI  - Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft
      Composition.
AB  - Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of
      post-hematopoietic stem cell transplantation (HSCT). Identifying patients at risk
      of severe aGVHD may lead to earlier intervention and treatment, resulting in
      increased survival and a better quality of life. We aimed to identify biomarkers
      in donor grafts and patient plasma around the time of transplantation that might
      be predictive of aGVHD development. We build on our previously published methods
      by using multiplex assays and multicolor flow cytometry. We identified 5 easily
      assessable cellular markers in donor grafts that combined could potentially be
      used to calculate risk for severe aGVHD development. Most noteworthy are the T
      cell subsets expressing IL-7 receptor-alpha (CD127) and PD-1. Additionally, we
      identified a potential role for elevated tumor necrosis factor-alpha levels in
      both graft and patient before HSCT in development of aGVHD.

PMID- 29197675
TI  - Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched
      Transplantation in Patients with Myeloid Leukemia.
AB  - Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after
      hematopoietic stem cell transplantation (HSCT) through their inhibitory killer
      cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C
      alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over
      HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese
      people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1)
      patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for
      hematologic malignancies by assessing the data of 10,638 patients from the
      Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than
      HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML)
      (hazard ratio [HR], .79; P = .006) and chronic myelogenous leukemia (CML) (HR,
      .48; P = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma
      (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML
      and CML patients together and divided them into several subgroups. Advantages of
      HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed
      irrespective of donor relation (related: HR, .79, P = .069; unrelated: HR, .77, P
      = .022), preparative regimen (myeloablative: HR, .79, P = .014; reduced
      intensity: HR, .73, P = .084), and occurrence of acute graft-versus-host disease
      (yes: HR, .70, P = .122; no, HR .71, P = .026) or cytomegalovirus reactivation
      (reactivated: HR .67,P = .054; nonreactivated: HR .71, P = .033); however, these
      advantages were not observed in recipients with a delay in achieving complete
      chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse
      free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell
      depleted HSCT (HR, .27; P < .001 and HR, .30; P = .002, respectively) and in
      children age <15 years (HR, .29; P < .001 and HR .31; P < .001, respectively).
      Our findings represent an important mechanism responsible for the immunity
      against HLA-C2-negative myeloid leukemia cells after HLA-matched transplantation.

PMID- 29197677
TI  - Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation
      Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling
      Allogeneic Peripheral Blood Stem Cell Transplantation.
AB  - Various approaches have been developed for ex vivo T cell depletion in allogeneic
      stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct
      comparisons of T cell depletion strategies have not been well studied, however.
      We evaluated cellular and plasma biomarkers in 2 different graft manipulation
      strategies, CD3+CD19+ cell depletion (CD3/19D) versus CD34+ selection (CD34S),
      and their associations with clinical outcomes. Identical conditions, including
      the myeloablative preparative regimen, HLA-identical sibling donor, GVHD
      prophylaxis, and graft source, were used in the 2 cohorts. Major clinical
      outcomes were similar in the 2 groups in terms of overall survival, nonrelapse
      mortality, and cumulative incidence of relapse; however, the cumulative incidence
      of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S
      cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher
      levels of ST2, impaired Helios- FoxP3+Treg reconstitution, and rapid
      reconstitution of naive, Th2, and Th17 CD4 cells in the early post
      transplantation period. In vitro graft replication studies confirmed that CD3/19D
      disproportionately depleted Tregs and other CD4 subset repertoires in the graft.
      This study confirms the utility of biomarker monitoring, which can be directly
      correlated with biological consequences and possible future therapeutic
      indications.

PMID- 29197678
TI  - Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation
      Survivors.
AB  - Adult survivors of acute leukemia in childhood have a higher-than-expected
      frequency of obesity and are at increased risk for metabolic syndrome and early
      mortality from cardiovascular disease (CVD). Adipose tissue has been recognized
      as an endocrine and paracrine organ that secretes various adipokines involved in
      metabolic regulation and inflammatory processes. In this study, we examined
      inflammatory factors (IL-6 and TNF-alpha) and adipokines (adiponectin, leptin),
      in addition to body composition and adiposity, in cancer survivors who underwent
      hematopoietic cell transplantation (HCT) during childhood compared with sibling
      controls. Over 2-year survivors of HCT for hematologic malignancies during
      childhood were recruited from 2 institutions along with a control population of
      siblings. Participants underwent evaluation for body composition, anthropometric
      measurements, and assessment of CVD risk factors and adipokines. Cases were
      stratified by radiation exposure in the preparative regimen (total body
      irradiation [TBI] + central nervous system [CNS] irradiation, TBI only,
      chemotherapy only) and adjusted least squares means were estimated for each
      adipokine and adjusted by age, sex, race, Tanner stage, and percent fat mass
      (PFM) percentiles (0-24, 25-74, 75+). A total of 151 HCT survivors and 92
      siblings underwent evaluation. Significant differences in mean adipokine levels
      were detected between survivors and siblings; leptin was significantly higher and
      adiponectin significantly lower in HCT survivors who received TBI with or without
      CNS irradiation compared with siblings. IL-6 was significantly higher in all
      groups of HCT survivors compared with siblings. Body mass index (BMI) was similar
      in survivors and controls, although PFM was significantly higher in all groups of
      HCT survivors and lean body mass (LBM) was lower in survivors who received TBI
      with or without CNS radiation compared with siblings. HCT survivors showed an
      unfavorable profile of inflammation, adipokines, and adiposity, despite similar
      BMI as controls. Higher PFM and lower LBM may contribute to these findings. TBI
      exposure is correlated with greater severity of these observations. Increasing
      LBM may represent a tangible target for mitigating the high cardiometabolic risks
      of HCT survivors.

PMID- 29197679
TI  - Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical
      Natural Killer Cells.
AB  - Natural killer (NK) cells mediate surveillance for malignancy. In some
      chemotherapy refractory myeloid leukemia patients, adoptive transfer of NK cells
      from haploidentical donors can induce remission. We have previously shown that
      remission induction is linked to NK cell persistence at day +14, but the factors
      influencing NK cell persistence are unknown. To address this question, patient
      samples from a phase I trial of National Cancer Institute (NCI) IL-15 in whom
      either did or did not show NK cell expansion were compared with healthy donor
      control subjects. Before lymphodepleting chemotherapy, high absolute CD3+ count
      was predictive of patients who failed to expand their haploidentical NK cell
      graft. Interestingly, both groups had elevated expression of inhibitory receptors
      and decreased cytokine production compared with control subjects, suggestive of T
      cell exhaustion among all patients before haploidentical NK cell infusion. At day
      +14, however, haploidentical NK cell expanders had persistence of recipient CD8+
      T cells with the most exhausted inhibitory phenotype (either PD-1high or dual PD
      1+Tim-3+) and elevated expression of T-bet and Eomes compared with NK cell
      nonexpanders and control subjects. This suggested that maintenance of an
      exhausted T cell state at day +14 permits haploidentical NK cell expansion and
      supports further efforts to selectively deplete recipient T cells or modulate
      their dysfunction.

PMID- 29197676
TI  - Intravenous Busulfan Compared with Total Body Irradiation Pretransplant
      Conditioning for Adults with Acute Lymphoblastic Leukemia.
AB  - Total body irradiation (TBI) has been included in standard conditioning for acute
      lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non
      TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This
      retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years
      old, in first or second complete remission (CR), undergoing HLA-compatible
      sibling, related, or unrelated donor HCT, who reported to the Center for
      International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus
      etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and
      intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%),
      or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed
      together, since no significant differences for patient outcomes were noted
      between them. Bu patients were older, with better performance status; took longer
      to achieve first CR and receive HCT; were treated more recently; and were more
      likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine
      kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for
      TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus
      TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free
      survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57%
      versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk
      of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002)
      compared with TBI patients. Despite the higher relapse, Bu-containing
      conditioning led to similar OS and DFS following HCT for ALL.

PMID- 29197680
TI  - Increased Coexpression of PD-1, TIGIT, and KLRG-1 on Tumor-Reactive CD8+ T Cells
      During Relapse after Allogeneic Stem Cell Transplantation.
AB  - Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for
      patients with a hematologic malignancy due to alloreactive T cell responses
      recognizing minor histocompatibility antigens (MiHA). Yet tumor immune escape
      mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells
      display low expression of costimulatory molecules and can up-regulate
      coinhibitory molecules that inhibit T cell functionality on ligation with their
      counter-receptors on the tumor-reactive T cells. The aim of this explorative
      study was to evaluate immune checkpoint expression profiles on T cell subsets and
      on cytomegalovirus (CMV)- and/or MiHA-reactive CD8+ T cells of allo-SCT
      recipients using a 13-color flow cytometry panel, and to correlate these
      expression patterns to clinical outcomes. MiHA-reactive CD8+ T cells exhibited an
      early differentiated CD27++/CD28++ phenotype with low KLRG-1 and CD57 expression.
      These T cells also displayed increased expression of PD-1, TIM-3, and TIGIT
      compared with total effector memory T cells and CMV-specific CD8+ T cells in
      healthy donors and allo-SCT recipients. Remarkably, high coexpression of PD-1,
      TIGIT, and KLRG-1 on MiHA-reactive CD8+ T cells was associated with relapse after
      allo-SCT. Taken together, these findings indicate that MiHA-specific CD8+ T cells
      of relapsed patients have a distinctive coinhibitory expression signature
      compared with patients who stay in remission. This phenotype may serve as a
      potential monitoring tool in patients. Moreover, these findings suggest that PD-1
      and TIGIT play important roles in regulating T cell-mediated tumor control,
      providing a rationale for immunotherapy with blocking antibodies to treat relapse
      after allo-SCT.

PMID- 29197681
TI  - T Cell-Replete Haploidentical Transplantation with Post-Transplantation
      Cyclophosphamide for Hodgkin Lymphoma Relapsed after Autologous Transplantation:
      Reduced Incidence of Relapse and of Chronic Graft-versus-Host Disease Compared
      with HLA-Identical Related Donors.
AB  - Allogeneic hematopoietic stem cell transplantation (SCT) represents a potential
      curative strategy for patients with Hodgkin lymphoma (HL) relapsing after
      autologous SCT (ASCT), but the incidence of disease relapse is still high. We
      performed a retrospective study on 64 patients with HL relapsing after ASCT to
      compare outcomes after HLA-identical SCT (HLAid-SCT; n = 34) and haploidentical
      SCT with post-transplantation cyclophosphamide (PT-Cy) (Haplo-SCT; n = 30). All
      patients engrafted, with a significantly shorter median time for neutrophil and
      platelet engraftment after HLAid compared with Haplo-SCT (14 days versus 19 days
      and 11 days versus 23 days, respectively; P < .005). With a median follow-up of
      47 months, 3-year overall survival (OS), 3 -year progression-free survival (PFS),
      and 1-year nonrelapse mortality (NRM) were 53%, 44% and 17%, respectively.
      Recipients of Haplo-SCT were less likely to experience disease relapse (3-year
      cumulative incidence of relapse, 13% versus 62%; P = .0001) and chronic graft-
      versus-host disease (GVHD; 3% versus 32%; P = .003), resulting in improved PFS
      (60% versus 29%; P = .04) and GVHD-free/relapse-free survival (47% versus 17%; P
      = .06). The 3-year OS did not differ between the 2 groups (56% versus 54%; P not
      significant), and NRM was higher after Haplo-SCT, but the difference did not
      reach statistical significance (26% versus 9%; P = .09). On multivariate Cox
      regression analysis, receipt of Haplo-SCT (hazard ratio [HR], .17; P = .02) and
      achieving optimal disease control (complete remission before SCT: HR, .6; P <
      .0001) were the only independent variables associated with a reduced risk of
      disease relapse. Haplo-SCT is a valid option for patients with HL relapsing after
      ASCT, with a reduced incidence of relapse compared with HLAid SCT.

PMID- 29197682
TI  - Prevalence of temporal bone pneumatization in relation to temporomandibular joint
      - A computed tomographic study.
AB  - BACKGROUND: Pneumatic spaces represent sites of minimal resistance, facilitating
      the spread of various pathological processes into the joint such as tumors,
      infection or fractures or vice versa. Considering the clinical importance of
      temporomandibular joint, prevalence of pneumatic spaces of the temporal bone in
      relation to TMJ in the roof of the TMJ fossa; articular eminence; zygomatic
      process and peritubal area was determined using Computed tomography. Laterality
      and gender wise prevalence of pneumatic spaces around the TMJ was also assessed.
      MATERIALS AND METHODS: A total of 100 high-resolution CT images of adult patients
      subjected to CT scan for the base of skull/temporal bone were utilized. Axial,
      reformatted coronal and sagittal images were analyzed on a DICOM viewer for the
      presence and distribution of pneumatic spaces of the temporal bone around TMJ in
      the roof of TMJ fossa, articular eminence, zygomatic process and peritubal area.
      RESULTS: The extent of pneumatization of the temporal bone varied considerably.
      The prevalence of pneumatization of the roof of the TMJ fossa was 52%, articular
      eminence (12%), the root of the zygomatic process (5%) and peritubal area was
      56%. Higher frequency of bilateral pneumatization was seen. No statistically
      significant correlation was seen in gender wise distribution of pneumatization.
      CONCLUSION: The present study revealed higher prevalence of pneumatization of
      temporal bone around TMJ. The knowledge of these air spaces is helpful for the
      interpretation of imaging studies and to understand the spread of pathological
      processes into the joint.

PMID- 29197684
TI  - Aridification driven diversification of fan-throated lizards from the Indian
      subcontinent.
AB  - The establishment of monsoon climate and the consequent aridification has been
      one of the most important climate change episodes in the Indian subcontinent.
      However, little is known about how these events might have shaped the
      diversification patterns among the widely distributed taxa. Fan-throated lizards
      (FTL) (Genus: Sitana, Sarada) are widespread, diurnal and restricted to the semi
      arid zones of the Indian subcontinent. We sampled FTL in 107 localities across
      its range. We used molecular species delimitation method and delineated 15
      species including six putative species. Thirteen of them were distinguishable
      based on morphology but two sister species were indistinguishable and have minor
      overlaps in distribution. Five fossils were used to calibrate and date the
      phylogeny. Diversification of fan-throated lizards lineage started ~18 mya and
      higher lineage diversification was observed after 11 my. The initial
      diversification corresponds to the time when monsoon climate was established and
      the latter was a period of intensification of monsoon and initiation of
      aridification. Thirteen out of the fifteen FTL species delimited are from
      Peninsular India; this is probably due to the landscape heterogeneity in this
      region. The species poor sister genus Otocryptis is paraphyletic and probably
      represents relict lineages which are now confined to forested areas. Thus, the
      seasonality led changes in habitat, from forests to open habitats appear to have
      driven diversification of fan-throated lizards.

PMID- 29197683
TI  - Long-range telomere regulation of gene expression: Telomere looping and telomere
      position effect over long distances (TPE-OLD).
AB  - The human cellular reverse transcriptase, telomerase, is very tightly regulated
      in large long-lived species. Telomerase is expressed during early human fetal
      development, is turned off in most adult tissues, and then becomes reactivated in
      almost all human cancers. However, the exact mechanism regulating these switches
      in expression are not known. We recently described a phenomenon where genes are
      regulated by telomere length dependent loops (telomere position effects over long
      distances; TPE-OLD). The hTERT gene is ~ 1.2Mb from the human chromosome 5p end.
      We observed that when telomeres are long hTERT gene expression is repressed and a
      probe next to the 5p telomere and the hTERT locus are spatially co-localized.
      When telomeres are short at least one of the hTERT alleles is spatially separated
      from the telomere, developing more active histone marks and changes in DNA
      methylation in the hTERT promoter region. These findings have implications for
      how cells turn off telomerase when telomeres are long during fetal development
      and how cancer cells reactivate telomerase in cells that have short telomeres. In
      addition to TPE-OLD, in proliferating stem cells such as activated T-lymphocytes,
      telomerase can be reversibly activated and silenced by telomere looping. In
      telomerase positive cancer cells that are induced to differentiate and
      downregulate telomerase, telomere looping correlates with silencing of the hTERT
      gene. These studies and others support a role of telomeres in regulating gene
      expression via telomere looping that may involve interactions with internal
      telomeric sequences (ITS). In addition to telomere looping, TPE-OLD may be one
      mechanism of how cells time changes in physiology without initiating a DNA damage
      response.

PMID- 29197685
TI  - Recession, employment and self-rated health: a study on the gender gap.
AB  - OBJECTIVES: Employment status and economic recession have been associated with
      negative effects on self-rated health, and this effect differs by gender. We
      analysed the effects of the Spanish economic recession in terms of self-rated
      health, its differential effect among genders and its influence on gender gap.
      STUDY DESIGN: Repeated cross-sectional study using Spanish health surveys (2001
      2014). METHODS: Logistic regression models were conducted to explore the
      association between self-rated health and employment status and its evolution
      over time and gender. To test the impact of the economic recession, pooled data
      regression models were conducted. RESULTS: In this study, we considered 104,577
      subjects. During the last 15 years, women have entered the labour market, leading
      to wide changes in the Spanish traditional family roles. Instead of an increasing
      proportion of women workers, gender employment differences persist. Therefore, in
      2014, the prevalence of workers was 55.77% in men, whereas in women, it was
      44.01%. Self-rated health trends during the economic recession differ by gender,
      with women improving slightly their self-rated health from a low self-rated
      health prevalence of 38.76% in 2001 to 33.78% in 2014. On the contrary, men seem
      more vulnerable to employment circumstances, which have led to substantial
      reduction in the gender gap. CONCLUSIONS: Although a gender gap persists, the
      change in socio-economic roles seems to increase women's self-rated health,
      reducing this gap. It is important to promote women's labour market inclusion,
      even in economic recession periods.

PMID- 29197686
TI  - The impact of screening on cancer incidence and mortality in Missouri, USA, 2004
      2013.
AB  - OBJECTIVES: Population-based evidence regarding impact of cancer screenings and
      cancer rates in Missouri is lacking. This study examined whether screenings of
      breast cancer, cervical cancer, and colorectal cancer impact early-stage cancer
      incidence and mortality in Missouri. STUDY DESIGN: This is an ecological study
      based on county-specific estimates of selected cancer screening prevalence and
      early-stage cancer incidence and cancer mortality. METHODS: County-specific
      prevalence of clinical breast examination, mammography, Pap test, sigmoidoscopy
      or colonoscopy, and fecal occult blood test (FOBT) were generated from Missouri
      County-Level Study (2003, 2007, and 2011). County-specific crude incidence and
      mortality were calculated (2004-2013). Pearson's correlation and Poisson
      regression were used to test association between cancer rate and screening
      prevalence. Covariates included county-level mean age, percentage of whites,
      percentage with low income, percentage with less than high school education high
      school, percentage with no insurance, and percentage having difficulties
      accessing care. RESULTS: In the adjusted model, 'ever had Pap test' was
      significantly associated with an increase of 8% in early-stage cervical cancer
      incidence. Having clinical breast examination or Pap test in the past was also
      associated with decreases in mortality by 3% and 4%, respectively, although the
      association was not significant for Pap test. In addition, having mammography was
      statistically significantly associated with early-stage breast cancer incidence,
      and having FOBT or sigmoidoscopy or colonoscopy was associated with decreased
      colorectal cancer mortality; however, magnitude for these associations was only
      around 1%. CONCLUSIONS: This study provides ecological evidence of the
      effectiveness of screening services in predicting early stage cancer incidence
      and in reducing mortality across Missouri counties. Further incentive to promote
      these screenings in Missouri is needed.

PMID- 29197687
TI  - A mixed methods evaluation of team-based learning for applied pathophysiology in
      undergraduate nursing education.
AB  - BACKGROUND: It is important for nurses to have a thorough understanding of the
      biosciences such as pathophysiology that underpin nursing care. These courses
      include content that can be difficult to learn. Team-based learning is emerging
      as a strategy for enhancing learning in nurse education due to the promotion of
      individual learning as well as learning in teams. OBJECTIVES: In this study we
      sought to evaluate the use of team-based learning in the teaching of applied
      pathophysiology to undergraduate student nurses. DESIGN: A mixed methods
      observational study. METHODS: In a year two, undergraduate nursing applied
      pathophysiology module circulatory shock was taught using Team-based Learning
      while all remaining topics were taught using traditional lectures. After the Team
      based Learning intervention the students were invited to complete the Team-based
      Learning Student Assessment Instrument, which measures accountability, preference
      and satisfaction with Team-based Learning. Students were also invited to focus
      group discussions to gain a more thorough understanding of their experience with
      Team-based Learning. Exam scores for answers to questions based on Team-based
      Learning-taught material were compared with those from lecture-taught material.
      RESULTS: Of the 197 students enrolled on the module, 167 (85% response rate)
      returned the instrument, the results from which indicated a favourable experience
      with Team-based Learning. Most students reported higher accountability (93%) and
      satisfaction (92%) with Team-based Learning. Lectures that promoted active
      learning were viewed as an important feature of the university experience which
      may explain the 76% exhibiting a preference for Team-based Learning. Most
      students wanted to make a meaningful contribution so as not to let down their
      team and they saw a clear relevance between the Team-based Learning activities
      and their own experiences of teamwork in clinical practice. Exam scores on the
      question related to Team-based Learning-taught material were comparable to those
      related to lecture-taught material. CONCLUSIONS: Most students had a preference
      for, and reported higher accountability and satisfaction with Team-based
      Learning. Through contextualisation and teamwork, Team-based Learning appears to
      be a strategy that confers strong pedagogical benefits for teaching applied
      pathophysiology (bioscience) to student nurses.

PMID- 29197688
TI  - Organizational learning in a college of nursing: A learning history.
AB  - BACKGROUND: College of nursing leaders can foster organizational learning as a
      means of achieving their desired organizational outcomes. Organizational learning
      has not previously been studied in colleges of nursing, leaving college
      administrators and faculty little guidance as they strive to improve outcomes in
      their own colleges. OBJECTIVES: The purpose of this study was to discover new
      insights related to organizational learning in a college of nursing. DESIGN: The
      learning history method was used to document and describe organizational learning
      in a college of nursing. SETTING: This study was conducted with a college of
      nursing situated in a private, religious-based university in the western United
      States. PARTICIPANTS: Six stakeholders and 16 individuals familiar with the
      college's history were purposively recruited for this study. Participants
      included college administrators, faculty, students, alumni, and individuals with
      university-level responsibilities related to the college. METHODS: Semi
      structured interviews and college artifacts were used to gather data. Data was
      reviewed and themes identified through a process called "distillation." FINDINGS:
      The college's vision, "Learning the Healer's Art" provides purpose and motivation
      within the college. Four themes provide additional insight into how the college
      established a learning culture and fosters behavior conducive to organizational
      learning: (1) Character and Quality, (2) Long-Term Perspective, (3) Collaborative
      Leadership and Adaptation, and (4) Mentoring. CONCLUSION: College of nursing
      leaders can foster organizational learning and pursue improvement within their
      colleges. Recommended actions include developing a shared vision for the college,
      building a cadre of qualified faculty and students who have strong personal
      character, maintaining a long-term perspective, using a collaborative approach to
      leadership and adaptation, and facilitating mentoring.

PMID- 29197689
TI  - Action research and millennials: Improving pedagogical approaches to encourage
      critical thinking.
AB  - BACKGROUND: This article examines the effects of intergenerational diversity on
      pedagogical practice in nursing education. While generational cohorts are not
      entirely homogenous, certain generational features do emerge. These features may
      require alternative approaches in educational design in order to maximize
      learning for millennial students. METHOD: Action research is employed with
      undergraduate millennial nursing students (n=161) who are co-researchers in that
      they are asked for changes in current simulation environments which will improve
      their learning in the areas of knowledge acquisition, skill development, critical
      thinking, and communication. These changes are put into place and a re-evaluation
      of the effectiveness of simulation progresses through three action cycles.
      RESULTS: Millennials, due to a tendency for risk aversion, may gravitate towards
      more supportive learning environments which allow for free access to educators.
      This tendency is mitigated by the educator modeling expected behaviors, followed
      by student opportunity to repeat the behavior. Millennials tend to prefer to work
      in teams, see tangible improvement, and employ strategies to improve inter
      professional communication. CONCLUSION: This research highlights the need for
      nurse educators working in simulation to engage in critical discourse regarding
      the adequacy and effectiveness of current pedagogy informing simulation design.
      Pedagogical approaches which maximize repetition, modeling, immersive feedback,
      and effective communication tend to be favored by millennial students.

PMID- 29197690
TI  - The first clinical practice experiences of psychiatric nursing students: A
      phenomenological study.
AB  - OBJECTIVE: The purpose of this study was to evaluate student nurses clinical
      experiences during their first clinical contacts with psychiatric patients by
      using a qualitative phenomenological approach. DESIGN: A phenomenological
      approach was used. Face-to-face interviews were conducted to collect data
      focusing on the reality of student nurses' experience. SETTINGS: This study was
      conducted at a university in the capital city of Turkey. PARTICIPANTS: The
      participants were undergraduate nursing students. A purposive sampling of 15
      students who had completed their first psychiatric clinical practicum was used in
      this study. METHODS: The data were collected by using unstructured interviews.
      The data were analysed by using Colaizzi's seven-step phenomenological method.
      RESULTS: Four themes were identified: theoretical information insufficient to
      break the stigma; breaking down the mental illness stigma; communication: the
      medication of mental illness; and personal development. CONCLUSION: At the end of
      clinical practice, stigma towards mental illness was reduced with empathy through
      the development of therapeutic relationships. The students stated that
      communication had a very important place in the treatment of mental illnesses and
      that psychiatric clinical practice helped them develop interpersonal relations.
      The results of this study can provide guidance for educators on the planning and
      development of clinical education.

PMID- 29197691
TI  - Cross or wait? Pedestrian decision making during clearance phase at signalized
      intersections.
AB  - Pedestrians arriving at clearance phase (Flashing Don't Walk) face different
      levels of risk depending on behavioral choice afterwards. However, few studies
      have focused on the choices pedestrians make during this phase. This field study
      analyzed pedestrian choices after arrival, evaluated safety of the choices, and
      built a model to identify the predictors of pedestrian choices. It was found that
      pedestrians arriving during clearance phase made dynamic decisions based on the
      changing contexts. Specifically, the majority made the decision to "cross" as
      opposed to "wait" (85.2% vs. 14.8% respectively), although only the latter choice
      is legal. Seventy-nine percent of the pedestrians did not finish crossing the
      intersection before the traffic light turned red, and they walked 41% of the road
      width during a red light. For those waited, roughly half of them waited until
      green or crossed at an intersecting crosswalk, while others finally started on
      red light. Nevertheless, the waited pedestrians still faced lower risk than those
      crossed prematurely in terms of running behaviors, and conflicts with vehicles.
      Pedestrians are more likely to cross immediately after arrival when they are
      younger, are not engaged in secondary tasks, arrived at a position farther from
      approaching vehicles at the near side of the road, or arrived at a time when
      there are more pedestrians crossing the road. Although fewer pedestrians choose
      to cross when the required speed is higher (due to a wider road or less remaining
      time), the required speed they choose to cross at is far higher than their actual
      speed. These findings are essential for realistic pedestrian simulations and
      targeted safety countermeasures. They also imply the need for changes to certain
      traffic regulations and signal design to facilitate safe decision making at
      clearance phase.

PMID- 29197692
TI  - Linking mind wandering tendency to risky driving in young male drivers.
AB  - Risky driving is a significant contributor to road traffic crashes, especially in
      young drivers. Transient mind wandering states, an internal form of distraction,
      are associated with faster driving, reduced headway distance, slower response
      times, reduced driver vigilance, and increased crash risk. It is unclear whether
      a trait tendency to mind wander predicts risky driving, however. Mind wandering
      is also associated with poor executive control, but whether this capacity
      moderates the putative link between mind wandering tendency and risky driving is
      uncertain. The present study tested whether mind wandering tendency predicts
      risky driving behaviour in young male drivers aged 18-21 (N=30) and whether this
      relationship is mediated by driver vigilance and moderated by executive control
      capacity. Mind wandering was measured with the Sustained Attention to Response
      Task (SART) and the Daydreaming Frequency Scale (DDFS). Risky driving was
      assessed by mean speed in a driving simulator and driver vigilance was quantified
      by horizontal eye movements measured with eye tracking. Results showed that
      greater mind wandering tendency based on SART performance significantly predicts
      faster mean speed, confirming the main hypothesis. Neither driver vigilance
      mediated nor executive control capacity moderated this relationship as
      hypothesized. These findings speak to the complexity of individual differences in
      mind wandering. Overall, mind wandering tendency is a significant marker of risky
      driving in young drivers, which could guide the development of targeted
      interventions.

PMID- 29197693
TI  - Longitudinal safety evaluation of electric vehicles with the partial wireless
      charging lane on freeways.
AB  - As an environment friendly transportation mode, the electric vehicle (EV) has
      drawn an increasing amount of attention from governments, vehicle manufactories
      and researchers recently. One of the biggest issue impeding EV's popularization
      associates with the charging process. The wireless charging lane (WCL) has been
      proposed as a convenient charging facility for EVs. Due to the high costs, the
      application of WCL on the entire freeways is impractical in the near future,
      while the partial WCL (PWCL) may be a feasible solution. This study aims to
      evaluate longitudinal safety of EVs with PWCL on freeways based on simulations.
      The simulation experiments are firstly designed, including deployment of PWCL on
      freeways and distribution of state of charge (SOC) of EVs. Then, a vehicle
      behavior model for EVs is proposed based on the intelligent driver model (IDM).
      Two surrogate safety measures, derived from time-to-collision (TTC), are utilized
      as indicators for safety evaluations. Sensitivity analysis is also conducted for
      related factors. Results show that the distribution of EVs' SOC significantly
      affect longitudinal safety when the PWCL is utilized. The low SOC in traffic
      consisting of EVs has the negative effect on longitudinal safety. The randomness
      and incompliance of EV drivers worsens the safety performance. The sensitivity
      analysis indicates that the larger maximum deceleration rate results in the
      higher longitudinal crash risks of EVs, while the length of PWCL has no
      monotonous effect. Different TTC thresholds also show no impact on results. A
      case study shows the consistent results. Based on the findings, several
      suggestions are discussed for EVs' safety improvement. Results of this study
      provide useful information for freeway safety when EVs are applied in the future.

PMID- 29197694
TI  - Experimental investigation of a metasurface resonator for in vivo imaging at 1.5
      T.
AB  - In this work, we experimentally demonstrate an increase in the local transmit
      efficiency of a 1.5 T MRI scanner by using a metasurface formed by an array of
      brass wires embedded in a high permittivity low loss medium. Placement of such a
      structure inside the scanner results in strong coupling of the radiofrequency
      field produced by the body coil with the lowest frequency electromagnetic
      eigenmode of the metasurface. This leads to spatial redistribution of the near
      fields with enhancement of the local magnetic field and an increase in the
      transmit efficiency per square root maximum specific absorption rate in the
      region-of-interest. We have investigated this structure in vivo and achieved a
      factor of 3.3 enhancement in the local radiofrequency transmit efficiency.

PMID- 29197695
TI  - Probing numerical Laplace inversion methods for two and three-site molecular
      exchange between interconnected pore structures.
AB  - Two-dimension (2D) Nuclear Magnetic Resonance relaxometry experiments are a
      powerful tool extensively used to probe the interaction among different pore
      structures, mostly in inorganic systems. The analysis of the collected
      experimental data generally consists of a 2D numerical inversion of time-domain
      data where T2-T2 maps are generated. Through the years, different algorithms for
      the numerical inversion have been proposed. In this paper, two different
      algorithms for numerical inversion are tested and compared under different
      conditions of exchange dynamics; the method based on Butler-Reeds-Dawson (BRD)
      algorithm and the fast-iterative shrinkage-thresholding algorithm (FISTA) method.
      By constructing a theoretical model, the algorithms were tested for a two- and
      three-site porous media, varying the exchange rates parameters, the pore sizes
      and the signal to noise ratio. In order to test the methods under realistic
      experimental conditions, a challenging organic system was chosen. The molecular
      exchange rates of water confined in hierarchical porous polymeric networks were
      obtained, for a two- and three-site porous media. Data processed with the BRD
      method was found to be accurate only under certain conditions of the exchange
      parameters, while data processed with the FISTA method is precise for all the
      studied parameters, except when SNR conditions are extreme.

PMID- 29197696
TI  - Small RNA differential expression and regulation in Tuxpeno maize embryogenic
      callus induction and establishment.
AB  - Somatic embryogenesis represents an alternative developmental process used to
      achieve genetic transformation and to approach key questions in maize
      development. It is known that embryogenic callus induction and plant regeneration
      are accompanied by microRNA expression changes. However, small RNA (sRNA)
      populations have not been explored during the proliferative callus subculture
      establishment and their impact on maintaining the dedifferentiated status and
      embryogenic potential is far from being completely understood. Here we globally
      tested the sRNA populations in explants (immature embryos), induced and
      established maize embryogenic callus from the Mexican cultivar VS-535, Tuxpeno
      landrace. We detected readjustments in 24 nt and 21-22 nt sRNAs during the
      embryogenic callus (EC) establishment and maintenance. A follow up on specific
      microRNAs (miRNAs) indicated that miRNAs related to stress response substantially
      increase upon the callus proliferation establishment, correlating with a
      reduction in some of their target levels. On the other hand, while 24 nt-long
      heterochromatic small interfering RNAs (hc-siRNAs) derived from transposable
      retroelements transiently decreased in abundance during the EC establishment, a
      population of 22 nt-hc-siRNAs increased. This was accompanied by reduction in
      transposon expression in the established callus subcultures. We conclude that
      stress- and development-related miRNAs are highly expressed upon maize EC callus
      induction and during maintenance of the subcultures, while miRNAs involved in
      hormone response only transiently increase during induction. In addition, the
      establishment of a proliferative status in embryogenic callus is accompanied by
      important readjustments in hc-siRNAs mapping to long tandem repeat (LTR)
      retrotransposons, and their expression regulation.

PMID- 29197697
TI  - The development of a spatial palliative care index instrument for assessing
      population-level need for palliative care services.
AB  - We developed an index to measure potential need for palliative care services
      (PCIX). This is an instrument that enables spatial identification of potential
      population-level need for palliative care services and can be developed using
      census data. Four indicators of potential need for palliative care services -age,
      sex, living arrangement, socio-economic status (SES)-were used to produce
      composite potential need scores for DAs. Scores were graphically mapped,
      producing a spatial delineation of relative need for end-of-life services. To
      assess the benefit of combining multiple variables to define potential need, PCIX
      resolution was compared to general SES-based delineations of need. PCIX scores
      and maps were generated for all DAs, revealing spatial variability in potential
      need for palliative care services (PCS). Comparison of PCIX maps to those based
      on purely on SES indicated that use of variables specifically linked to
      palliative need resulted in more precise delineations of potential populations in
      need of PCS. Using composite scores - based on freely available census data - to
      spatially assess potential need for palliative care services can provide critical
      data for decision makers charged with rationalizing service locations and service
      capacity.

PMID- 29197698
TI  - Emergence of shared reference and shared minds in infancy.
AB  - The emergence of a social-interactional 'infrastructure' of communication in
      infancy has remained underspecified until recently. I argue and show that
      firstly, the ability for shared reference is firmly established around 12 months
      of age when infants begin to point, enabling a meeting of shared minds; secondly,
      interactions entailing different perspectives and minds emerge only thereafter,
      based on prior interactional experiences; thirdly, the emergence of shared
      reference is itself mediated by interaction and caregivers' assistance in goal
      directed activities. Instead of focusing on the infrastructure of shared
      reference in infancy as a snapshot, I suggest focusing on the process of social
      and cognitive co-construction in which shared reference is as much a foundation
      as an ontogenetic outcome of social cognition and interaction.

PMID- 29197699
TI  - What is unique about shared reality? Insights from a new comparison species.
AB  - We introduce a new comparison species-domesticated dogs (Canis familaris)-that
      can shed light on the evolutionary origins of shared reality. Given that dogs
      share many basic building blocks of shared reality (e.g. representing others'
      perceptions, emotions, and behaviors) they provide an ideal species for
      pinpointing unique aspects of shared reality in humans. In particular, current
      research with dogs underscores two aspects of shared reality that may be special
      to humans. First, humans may be unique in our tendency to share reality
      involuntarily. Second, humans may be unique in the extent to which we share
      reality. Although both humans and dogs share reality in one-on-one interactions,
      only humans share reality at the more extensive group and cultural level.

PMID- 29197700
TI  - Romantic relationships as shared reality defense.
AB  - A model of meaning maintenance in relationships is proposed to explain how
      relationships function to regulate threats to shared systems of meaning posed by
      life's capricious and unexpected events. This model assumes that people
      flexibility compensate for unexpected events in the world by affirming the
      expected in their relationship and compensate for unexpected events in the
      relationship by affirming the expected in the world. Supportive evidence is
      reviewed that reveals how people in more or less satisfying relationships
      flexibly maintain a sense of life's meaning in the face of unexpected events.

PMID- 29197701
TI  - The contribution of parental and societal conditional regard to adjustment of
      high school dropouts.
AB  - This study examined the contribution of parental conditional regard (PCR) and
      societal conditional regard (SCR) - divided into positive and negative regard -
      to high school dropouts' adjustment (i.e., well-being, loneliness, and future
      orientation) along the different stages of the dropout process. Specifically, the
      current study focused on dropouts from a traditional community, where dropping
      out was accompanied by various social repercussions. The study, conducted in
      Israel among Ultraorthodox Jewish males, included 261 participants, ages 14-21 (M
      = 17, SD = 1.17), who were at different stages in the dropout process. Structural
      equation modeling indicated a negative contribution of parental conditional
      negative regard to adjustment, while societal conditional positive regard made a
      positive contribution to adjustment. Moreover, dropouts indicated higher parental
      and societal conditional regard than students at other stages of the dropout
      process. Findings highlight the importance of SCR and PCR in understanding the
      adjustment of dropouts in traditional communities.

PMID- 29197702
TI  - Longitudinal relations between adolescents' materialism and prosocial behavior
      toward family, friends, and strangers.
AB  - The present study examines the short-term changes and longitudinal relations
      between adolescents' materialism and prosocial behavior toward family, friends,
      and strangers over a year. A total of 434 Chinese adolescents (mean age at Time 1
      = 11.27; 54% girls) participated in the two time points. From 6th grade to 7th
      grade, boys' and girls' materialism increased, whereas their prosocial behavior
      toward family, friends, and strangers declined, despite the stable trend in boys'
      prosocial behavior toward strangers. Furthermore, a cross-lagged model was
      conducted and the results showed that, adolescent materialism was associated
      longitudinally with decreased prosocial behavior toward friends and strangers,
      but not toward family. However, earlier prosocial behavior toward family,
      friends, and strangers were not associated with subsequent adolescent
      materialism. The findings point toward an understanding of materialism as a
      precursor rather than an outcome or byproduct to prosocial behavior.

PMID- 29197703
TI  - Emotional lability and affective synchrony in posttraumatic stress disorder
      pathology.
AB  - This study examined the relations of PTSD pathology to both the lability of three
      specific emotions (anxiety, anger, self-conscious emotions [SCE]) and the extent
      to which changes in one emotional state co-occur with changes in another
      emotional state (i.e. affective synchrony). Moreover, given evidence that
      emotional responding in PTSD may be heightened in response to trauma-related
      cues, these relations were explored in the context of a trauma cue versus neutral
      cue. Trauma-exposed patients in residential substance use disorder treatment
      (N=157) completed a diagnostic interview and two laboratory sessions involving
      presentation of neutral and individualized trauma scripts. State anxiety, anger,
      and SCE were assessed at five points throughout each laboratory session.
      Hierarchical linear modeling indicated that participants (regardless of PTSD
      status) exhibited greater lability of all emotions following the trauma script
      versus neutral script. Only anger lability was elevated among those with (versus
      without) a current PTSD diagnosis following the neutral script. Results also
      revealed synchrony (i.e., positive covariation) between each possible pair of
      emotions, regardless of PTSD status. Findings suggest that concurrent changes in
      anxiety and anger may be especially relevant to PTSD symptom severity.

PMID- 29197705
TI  - A real-time and registration-free framework for dynamic shape instantiation.
AB  - Real-time 3D navigation during minimally invasive procedures is an essential yet
      challenging task, especially when considerable tissue motion is involved. To
      balance image acquisition speed and resolution, only 2D images or low-resolution
      3D volumes can be used clinically. In this paper, a real-time and registration
      free framework for dynamic shape instantiation, generalizable to multiple
      anatomical applications, is proposed to instantiate high-resolution 3D shapes of
      an organ from a single 2D image intra-operatively. Firstly, an approximate
      optimal scan plane was determined by analyzing the pre-operative 3D statistical
      shape model (SSM) of the anatomy with sparse principal component analysis (SPCA)
      and considering practical constraints. Secondly, kernel partial least squares
      regression (KPLSR) was used to learn the relationship between the pre-operative
      3D SSM and a synchronized 2D SSM constructed from 2D images obtained at the
      approximate optimal scan plane. Finally, the derived relationship was applied to
      the new intra-operative 2D image obtained at the same scan plane to predict the
      high-resolution 3D shape intra-operatively. A major feature of the proposed
      framework is that no extra registration between the pre-operative 3D SSM and the
      synchronized 2D SSM is required. Detailed validation was performed on studies
      including the liver and right ventricle (RV) of the heart. The derived results
      (mean accuracy of 2.19 mm on patients and computation speed of 1 ms) demonstrate
      its potential clinical value for real-time, high-resolution, dynamic and 3D
      interventional guidance.

PMID- 29197704
TI  - Participation in the Supplemental Nutrition Assistance Program and maternal
      depressive symptoms: Moderation by program perception.
AB  - RATIONALE: Previous studies have observed an association between participation in
      the Supplemental Nutrition Assistance Program (SNAP) and depression, which is
      contrary to SNAP's potential to alleviate food insecurity and financial strain.
      OBJECTIVE: This study investigated the impact of change in SNAP participation
      status on maternal depression, and whether perceptions of government assistance
      moderate this association. METHODS: Data were from the Fragile Families and Child
      Wellbeing Study (FFCWS). Logistic regression models with individual-specific
      fixed-effects, were fit to SNAP-eligible mothers who changed SNAP participation
      and depression status (N = 256) during waves 2 to 4. Perceptions of government
      assistance were defined as feelings of humiliation or loss of freedom and tested
      for interactions with SNAP participation. RESULTS: Perceptions of government
      assistance moderated the association between SNAP participation and depression (p
      interaction = 0.0208). Those with positive perceptions of welfare had 0.27 (95%
      CI = 0.08 to 0.89) times lower odds of depression when enrolled vs. not enrolled
      in SNAP. Among those with negative perceptions of welfare, SNAP enrollment was
      not associated with depression (OR = 1.13; 95% CI = 0.85 to 1.51). CONCLUSION:
      Evidence suggests that SNAP mental health benefits may be context specific.
      SNAP's capacity to improve mental health may depend on individual perceptions of
      government assistance. More research is needed to determine whether interventions
      aimed at mitigating negative perceptions of programs like SNAP could ameliorate
      poor mental health among program participants.

PMID- 29197706
TI  - Exploring the experiences of neophyte nurse mentors: A qualitative study.
AB  - Mentoring has become an increasingly popular supportive method for empowering
      nurses and assisting them to progress in their careers. Evidence from the
      literature demonstrates that not all experienced and highly qualified nurses are
      effective mentors. The aim of this study was to explore and describe the
      experiences of neophyte nurse mentors following their first formal mentoring
      relationship using a qualitative exploratory design. Data were collected using
      dual moderated focus group methods. The focus group was digitally recorded and
      transcribed verbatim. Interviews were analysed using thematic analysis. Six
      neophyte nurse mentors participated in the focus group. The themes identified
      included (1) Readiness for mentoring, (2) Venturing into the unknown, (3) Having
      the right fit (4) Frustrations of mentoring (5) Reciprocal professional
      relationship. The findings highlight how neophyte nurse mentors perceive
      mentoring and the importance of providing them with adequate preparation and
      support in order to efficiently transfer valuable knowledge and skills to their
      mentees.

PMID- 29197707
TI  - Cancelling pesticide registrations and revoking tolerances: The case of
      chlorpyrifos.
AB  - Petitions submitted to the United States Environmental Protection Agency (EPA)
      have sought to cancel registrations of chlorpyrifos and to revoke chlorpyrifos
      tolerances in or on food due to adverse health effects on people. Under federal
      law, tolerances for pesticide chemical residues in or on food must provide with
      reasonable certainty that no harm will result from a person's aggregate exposure.
      Petitioners' claims are analyzed under the legal requirements to discern whether
      the EPA had a rational basis for issuing its 2017 Chlorpyrifos Order denying the
      requests for cancellation of registrations and revocation of tolerances. The
      scientific evidence considered by the EPA indicated that existing tolerances do
      not protect people from unsafe levels of chlorpyrifos. Under the Federal Food,
      Drug, and Cosmetic Act, tolerances need to be revoked if they do not protect
      human health. In refusing to recognize that chlorpyrifos tolerances do not comply
      with federal law, the EPA's 2017 Chlorpyrifos Order appears to be arbitrary and
      capricious.

PMID- 29197708
TI  - Mother-infant separation among mothers with mental illness: An exploratory
      observational study in Japan.
AB  - Mother-infant separation may influence child development and behavior problems.
      We reviewed charts for 3639 female patients to investigate rates, reasons, and
      predictors for mothers with mental illness being separated from their infants
      during the first year after childbirth in Japan. Of 77 patients with childbirth,
      26 cases (34%) presented with maternal separation. The most common reason was
      psychiatric hospitalization. Diagnoses of schizophrenia spectrum disorders or
      mood disorders were independent contributors for maternal separation. Clinicians
      should pay particular attention to relapse or onset of psychotic or mood
      disorders during the perinatal period.

PMID- 29197709
TI  - Family history of psychosis and outcome of people with schizophrenia in rural
      China: 14-year follow-up study.
AB  - OBJECTIVE: This study examined the differences in 14-year outcomes of persons
      with schizophrenia with and without family history of psychosis in a rural
      community in China. METHODS: All participants with schizophrenia (n=510) aged 15
      years and older were identified in a 1994 epidemiological investigation of
      123,572 people and followed up in 2004 and 2008 in Xinjin County, Chengdu, China.
      RESULTS: Individuals with positive family history of schizophrenia had
      significantly younger age of first onset than those with negative family history
      of schizophrenia in 1994 and 2004. Compared with individuals with negative family
      history of schizophrenia, those with positive family history of schizophrenia had
      significantly higher rate of homelessness and lower rate of death due to other
      reasons in 10-year (2004) and 14-year follow-up (2008). There were no
      significantly differences of mean scores on PANSS, SDSS and GAF in 2008 between
      positive and negative family history groups. CONCLUSIONS: The positive family
      history of schizophrenia is strongly related to younger age of onset, and may
      predict a poorer long-term outcome (e.g., higher rate of homelessness) in persons
      with schizophrenia in the rural community. The findings have implications for
      further studies on specific family-related mechanisms on clinical treatment and
      rehabilitation, as well as for planning and delivering of community-based mental
      health services.

PMID- 29197710
TI  - ECT in Schizophrenia: Does indication affect the outcome?

PMID- 29197711
TI  - Prevalence of sleep disorders and severity of insomnia in psychiatric outpatients
      attending a tertiary level mental health care facility in Punjab, India.
AB  - BACKGROUND: Sleep disorders are frequently associated with psychiatric disorders
      and can be both cause and effect of the same. AIM: To study the prevalence of
      sleep disorders and the severity of insomnia in psychiatric outpatients. METHODS:
      500 patients were randomly selected using purposive sampling from patients
      attending a tertiary level mental health care facility were evaluated for the
      presence of any sleep disorder along with their sleep quality. In patients having
      insomnia, severity of the same was determined. RESULTS: 83.4% of the population
      had some type of sleep disorder. Symptoms of insomnia were reported by 78.2% of
      the population and 29.2% had moderate to severe insomnia. 78.4% of the population
      had poor sleep quality. Significant difference was noted among the different
      psychiatric groups when insomnia severity index (ISI) was compared. In
      multinomial logistic regression, chance of severe insomnia is more if the
      diagnosis is depression, but less if mania or ocd, compared to psychosis.
      CONCLUSION: This study was the first in India to assess the prevalence of sleep
      disorders in psychiatric outpatients. Our study underscores the importance of
      careful evaluation of sleep problems for proper management of the patients.

PMID- 29197712
TI  - Radiotherapy-induced reactivation of neurotrophic human herpes viruses: Overview
      and management.
AB  - PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent
      throughout the world. It is known that radiotherapy can reactivate HHVs, but it
      is unclear how and to what extent reactivations can interact with or affect
      radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to
      summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster
      Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo
      radiotherapy, diagnosis and management so as to optimize cancer treatment in the
      setting of active HHV infection. Our secondary aim is to emphasize the need for
      further research to elucidate the potential adverse effects of active HHV
      infection in irradiated tumor tissue and to design optimal management strategies
      to incorporate into cancer management guidelines. MATERIALS AND METHODS: The
      literature regarding herpetic infection, herpetic reactivation, and recurrence
      occurring during radiotherapy and that regarding treatment guidelines for
      herpetic infections are reviewed. We aim to provide the oncologist with a
      reference for the infectious dangers of herpetic reactivation in patients under
      their care and well established methods for prevention, diagnosis, and treatment
      of such infections. Pain management is also considered. CONCLUSIONS: In the
      radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and
      can alert the clinician to patients at risk for viral reactivation. RT-PCR is
      specific in identifying the exact viral culprit and is the preferred diagnostic
      method to measure interventional efficacy. It can also differentiate between
      herpetic infection and radionecrosis. The MicroTrak(r) HSV1/HSV2/VZV staining kit
      has high sensitivity and specificity in acute lesions, is also the most rapid
      means to confirm diagnosis. Herpetic reactivation and recurrences during
      radiotherapy can cause interruptions, cessations, or prolongations of the
      radiotherapeutic course, thus decreasing the biologically effective dose, to sub
      therapeutic levels. Active HHV infection within the treatment volume results in
      increased tumor radio-resistance and potentially sub-therapeutic care if left
      untreated. Visceral reactivations may result in fatality and therefore, a high
      index of suspicion is important to identify these active infections. The fact
      that such infections may be mistaken for acute and/or late radiation effects,
      leading to less than optimal treatment decisions, makes knowledge of this problem
      even more relevant. To minimize the risk of these sequelae, prompt anti-viral
      therapy is recommended, lasting the course of radiotherapy.

PMID- 29197713
TI  - Development of a simultaneous identification method for 13 animal species using
      two multiplex real-time PCR assays and melting curve analysis.
AB  - We developed a simple and rapid method for animal species identification in the
      forensic science field based on mitochondrial DNA using two multiplex real-time
      PCRs and analysis of the resultant SYBR Green I melting curves. This method was
      designed to identify nine domestic animals simultaneously (dog, cat, rabbit,
      cattle, pig, chicken, goat, sheep and horse) and four wild animals (deer, raccoon
      dog, monkey and bear) by comparing the different melting temperatures of the
      amplicons produced from samples originating from each species. For this analysis,
      we targeted various mitochondrial genes, including those encoding cytochrome b
      (cytb), NADH dehydrogenase 5 (ND5), cytochrome c oxidase 3 (COX3), tRNA-ND5, and
      tRNA-ATP synthase 8 (ATP8). For practical applications, this study presents a
      validation of this assay including its specificity, sensitivity and robustness.
      The limits of detection in the multiplex reactions were 10 pg for eight of the
      nine animals, excluding horse (1 pg for horse). The method was able to correctly
      identify the animal species from artificial forensic samples including blood
      stains, saliva, hair and bone, and samples digested in artificial gastric fluid,
      and for 17 forensic casework samples. The data from the multiplex real-time PCR
      assays are obtainable only 30 min after DNA extraction of the samples, making the
      assays useful for screening samples containing DNA from unknown animal origin in
      the forensic field.

PMID- 29197714
TI  - Effect of cadmium exposure on hepatopancreas and gills of the estuary mud crab
      (Scylla paramamosain): Histopathological changes and expression characterization
      of stress response genes.
AB  - Cadmium (Cd) is a heavy metal that accumulates easily in organisms and causes
      several detrimental effects, including tissue damage. Cd contamination from
      anthropogenic terrestrial sources flows into rivers, and through estuaries to the
      ocean. To evaluate the toxic effects of Cd on estuary crustaceans, we exposed the
      mud crab Scylla paramamosain to various Cd concentrations (0, 10.0, 20.0, and
      40.0mg/L) for 24h. We also exposed mud crabs to a fixed Cd concentration
      (20.0mg/L) for various periods of time (0, 6, 12, 24, 48, and 72h). We observed
      that after exposure to Cd, the surfaces of the gill lamellae were wrinkled, and
      the morphologies of the nuclei and mitochondria in the hepatopancreas were
      altered. We analyzed the expression profiles of 36 stress-related genes after Cd
      exposure, including those encoding metallothioneins, heat shock proteins,
      apoptosis-related proteins, and antioxidant proteins, with quantitative reverse
      transcription PCR. We found that exposure to Cd altered gene expression, and that
      some genes might be suitable bioindicators of Cd stress. Gene expression profiles
      were organ-, duration-, and concentration-dependent, suggesting that stress
      response genes might be involved in an innate defense system for handling heavy
      metal exposure. To the best of our knowledge, this study is the first one of
      histopathology and stress-response gene expression pattern of Scylla paramamosain
      after Cd exposure. Our work could increase our understanding of the effect of
      environmental toxins on estuary crustaceans.

PMID- 29197715
TI  - End-of-life care of elderly patients with dementia: A cross-sectional study of
      family carer decision-making.
AB  - BACKGROUND: Dementia syndromes pose a major worldwide challenge to public health.
      In terminal stage of dementia, carers are responsible for decision making in end
      of-life treatment and there may be multiple factors that contribute to the choice
      of a palliative or invasive treatment. AIM: To identify possible factors that
      influence the decision-making of family caregivers on implementing invasive or
      palliative interventions for people with end stage dementia. DESIGN: A structured
      interview with family caregivers of elderly patients addressing aspects of the
      following categories: elderly with dementia, caregiver, medical treatment
      history. Statistical analysis was performed to test whether there was a
      significant association between the carer's decision (invasive or palliative
      treatment) and the collected variables. SETTINGAND PARTICIPANTS: The study was
      conducted in three hospitals in Brazil. Participants were family caregivers of
      inpatients with end stage dementia RESULTS: Most of caregivers chose not to
      perform invasive procedures. The factors with the greatest association with the
      decision for invasive care were: elderly with tracheostomy, dementia diagnosis
      for less than 2 years, caregiver's age less than 50 years, history of hospital
      admission in the last year, affirmation that interviewee would be surprised with
      the death of the elderly within 1year and the denial that health care team has
      already explained about treatment options. CONCLUSION: There were identified
      several factors related to the carer, the elderly person and their medical
      treatment that may influence the choice between palliative and invasive care for
      the elderly person with dementia.

PMID- 29197716
TI  - Understanding organization transformation in evaluation and program planning.
AB  - Organization transformation is an increasingly important concept and process in
      human service organizations as they adapt to rapidly changing challenges and
      opportunities to enhance their effectiveness, efficiency, and sustainability.
      This article describes a four-component organization transformation model that
      incorporates transformation pillars, transformation strategies, organization
      capacity, and organization outputs and outcomes. The article includes examples of
      the model's use, and concludes with a discussion of valuable lessons learned to
      date.

PMID- 29197717
TI  - Inferring Chinese surnames with Y-STR profiles.
AB  - Co-ancestry of human surnames and Y-chromosomes in most human populations and
      social groups suggests the possibility of inferring one from the other. However,
      such an intuitive perspective remains to be formally explored. In the present
      study, we develop two computational methods, based on cosine distance (dcos) and
      coalescence distance (dcoal) respectively, to infer surnames from Y-STR profiles.
      We also survey Y-STR variations at 15 loci for 19,009 individuals of Shandong
      Province in China. For a total of 266 surnames included in the data set, our
      methods can pinpoint to a single surname with an average accuracy of 65%, and
      with an average accuracy higher than 80% when providing >4 candidate surnames. We
      also demonstrate that increasing the sample size of surnames and the number of
      STR loci improves the accuracy of surname inference. Our results indicate that
      the 15 non-duplicated Y-STR loci contain information from which surname can be
      reliably inferred for Chinese populations, showing a promising application in
      forensics.

PMID- 29197718
TI  - The mechanisms of K. lactis Cdc13 in telomere DNA-binding and telomerase
      regulation.
AB  - Eukaryotic chromosome ends, or telomeres, are essential for genome stability and
      are protected by an intricate nucleoprotein assembly. Cdc13, the major single
      strand telomere-binding protein in budding yeasts, mediates critical functions in
      both telomere protection and telomere elongation by telomerase. In particular,
      the interaction between S. cerevisiae Cdc13 and telomerase subunit Est1 has long
      served as a paradigm for telomerase regulation. However, despite extensive
      investigations, the role of this interaction in regulating telomerase recruitment
      or activation remains controversial. In addition, budding yeast telomere repeat
      sequences are extraordinarily variable and how Cdc13 orthologs recognize diverse
      repeats is not well understood. In this report, we examined these issues using an
      alternative model, K. lactis. We reconstituted a direct physical interaction
      between purified K. lactis Cdc13 and Est1, and by analyzing point mutations, we
      demonstrated a close correspondence between telomere maintenance defects in vivo
      and Cdc13-Est1 binding defects in vitro, thus supporting a purely recruitment
      function for this interaction in K. lactis. Because mutations in well aligned
      residues of Cdc13 and Est1 in S. cerevisiae and K. lactis do not cause identical
      defects, our results also point to significant evolutionary divergence in the
      Cdc13-Est1 interface. In addition, we found that K. lactic Cdc13, unlike
      previously characterized orthologs, recognizes an unusually long and non-G-rich
      target sequence, underscoring the flexibility of the Cdc13 DNA-binding domain.
      Analysis of K. lactis Cdc13 and Est1 thus broadens understanding of telomere and
      telomerase regulation in budding yeast.

PMID- 29197719
TI  - Functional diversification upon leader protease domain duplication in the Citrus
      tristeza virus genome: Role of RNA sequences and the encoded proteins.
AB  - Viruses from the family Closteroviridae show an example of intra-genome
      duplications of more than one gene. In addition to the hallmark coat protein gene
      duplication, several members possess a tandem duplication of papain-like leader
      proteases. In this study, we demonstrate that domains encoding the L1 and L2
      proteases in the Citrus tristeza virus genome underwent a significant functional
      divergence at the RNA and protein levels. We show that the L1 protease is crucial
      for viral accumulation and establishment of initial infection, whereas its coding
      region is vital for virus transport. On the other hand, the second protease is
      indispensable for virus infection of its natural citrus host, suggesting that L2
      has evolved an important adaptive function that mediates virus interaction with
      the woody host.

PMID- 29197720
TI  - ZikaBase: An integrated ZIKV- Human Interactome Map database.
AB  - Re-emergence of ZIKV has caused infections in more than 1.5 million people. The
      molecular mechanism and pathogenesis of ZIKV is not well explored due to
      unavailability of adequate model and lack of publically accessible resources to
      provide information of ZIKV-Human protein interactome map till today. This study
      made an attempt to curate the ZIKV-Human interaction proteins from published
      literatures and RNA-Seq data. 11 direct interaction, 12 associated genes are
      retrieved from literatures and 3742 Differentially Expressed Genes (DEGs) are
      obtained from RNA-Seq analysis. The genes have been analyzed to construct the
      ZIKV-Human Interactome Map. The importance of the study has been illustrated by
      the enrichment analysis and observed that direct interaction and associated genes
      are enriched in viral entry into host cell. Also, ZIKV infection modulates 32%
      signal and 27% immune system pathways. The integrated database, ZikaBase has been
      developed to help the virology research community and accessible at
      https://test5.bicpu.edu.in.

PMID- 29197721
TI  - Comparative evaluation of three capripoxvirus-vectored peste des petits ruminants
      vaccines.
AB  - Sheep and goat pox (SGP) with peste des petits ruminants (PPR) are transboundary
      viral diseases of small ruminants that cause huge economic losses. Recombinant
      vaccines that can protect from both infections have been reported as a promising
      solution for the future. SGP was used as a vector to express two structural
      proteins hemagglutinin or the fusion protein of PPRV. We compared immunity
      conferred by recombinant capripoxvirus vaccines expressing H or F or both HF.
      Safety and efficacy were evaluated in goats and sheep. Two vaccine doses were
      tested in sheep, 104.5TCDI50 in 1ml dose was retained for the further experiment.
      Results showed that the recombinant HF confers an earlier and stronger immunity
      against both SGP and PPR. This recombinant vaccine protect also against the
      disease in exposed and unexposed sheep. The potential Differentiating Infected
      from Vaccinated Animals of recombinant vaccines is of great advantage in any
      eradication program.

PMID- 29197722
TI  - Tracking internet interest in anabolic-androgenic steroids using Google Trends.

PMID- 29197723
TI  - The flavonoid quercetin inhibits titanium dioxide (TiO2)-induced chronic
      arthritis in mice.
AB  - Titanium dioxide (TiO2) is a common component of orthopedic prosthesis. However,
      prosthesis wear releases TiO2, which induces inflammation and osteolysis in peri
      prosthetic tissues. Quercetin is a flavonoid widely present in human diet, which
      presents biological activities such as antinociceptive, anti-inflammatory and
      antioxidant effects. Therefore, the effect of intraperitoneal treatment with
      quercetin in TiO2-induced arthritis model was evaluated. In the first set of
      experiments, mice received injection of TiO2 (0.1-3 mg/knee joint) and articular
      mechanical hyperalgesia, edema and histopathology analysis were performed in a 30
      days protocol. The dose of 3 mg of TiO2 showed the most harmful effect, and was
      chosen to the following experiments. Subsequently, mice received 3 mg of TiO2
      followed by post-treatment with quercetin during 30 days. Quercetin (10-100
      mg/kg) inhibited in a dose-dependent manner TiO2-induced knee joint mechanical
      hyperalgesia, edema and leukocyte recruitment and did not induce damage in major
      organs such as liver, kidney and stomach. The dose of 30 mg/kg was chosen for the
      subsequent analysis, and reduced histopathological changes such as leukocyte
      infiltration, vascular proliferation and synovial hyperplasia (pannus formation)
      on day 30 after TiO2 challenge. The protective analgesic and anti-inflammatory
      mechanisms of quercetin included the inhibition of TiO2-induced neutrophil and
      macrophage recruitment, proteoglycan degradation, oxidative stress, cytokine
      production (TNF-alpha, IL-1beta, IL-6, and IL-10), COX-2 mRNA expression, and
      bone resorption as well as activation of Nrf2/HO-1 signaling pathway. These
      results demonstrate the potential therapeutic applicability of the dietary
      flavonoid quercetin to reduce pain and inflammatory damages associated with
      prosthesis wear process-induced arthritis.

PMID- 29197724
TI  - Follicular response and oocyte production following variations in ovarian
      stimulation in goats.
AB  - In this study, goats were subjected to ovarian stimulation protocols to evaluate
      possible differences in ovarian follicular responses and oocyte production. Two
      experiments were conducted to assess the effects of hormonal protocol duration
      (seven or twelve days) and number of follicle stimulating hormone (FSH)
      applications (one or five doses). All animals received intravaginal sponges
      saturated with 60 mg medroxyprogesterone acetate and an application of 125 MUg
      cloprostenol 72 h before the sponges were removed. For ovarian stimulation, 120
      mg FSH was applied in a single dose 36 h before laparoscopic follicular
      aspiration (LOPU) or in five doses (30, 30, 20, 20, and 20 mg) at 12 h intervals,
      with the last dose applied 36 h before LOPU. In the first experimental phase,
      ultrasonography was performed to monitor follicular number and diameter, and in
      the second phase, the animals received LOPU to count the follicles and cumulus
      oocyte complexes (COCs) and for morphological classification. There was no
      significant effect (P > 0.05) of any variable or combination of variables on
      follicle number on Day (D) 0 or D3/D8 (day of LOPU). However, evaluation at
      D6/D11 revealed an effect (P < 0.05) from the protocol duration with the highest
      number of small follicles resulting from the short protocol. There was also an
      effect (P < 0.05) of FSH dose number on the resulting number of medium and large
      follicles, with more medium follicles recovered after a single dose and more
      large follicles after multiple doses. There was no effect of any variable (P >
      0.05) on the diameters of the large, medium, and small follicles, except for the
      D4/D9 evaluation, which showed a combination effect for large follicles (P <
      0.05). In the second phase, no variable had an effect on the number of follicles
      visualized or aspirated, number of COCs recovered, recovery rate, morphological
      quality of COCs in grades 1, 2, 3, and 4, or rate of viable COCs. Thus, all four
      protocols efficiently stimulated the ovarian response and oocyte production of
      goats, although the short protocol (7 days) with a single dose of FSH was most
      efficacious based upon the greater number of medium-sized follicles available for
      aspiration, the shorter time, and greater practicality of execution.

PMID- 29197725
TI  - Exploring the selectivity of inhibitor complexes with Bcl-2 and Bcl-XL: A
      molecular dynamics simulation approach.
AB  - B-cell lymphoma 2 (Bcl-2) family proteins are potential drug targets in cancer
      and have a relatively flat and flexible binding site. ABT-199 is one of the most
      promising selective Bcl-2 inhibitors, and A-1155463 selectively inhibits Bcl-XL.
      Although the amino acid sequences of the binding sites of these two inhibitors
      are similar, the inhibitors selectively bind the target protein. In order to
      determine the origin of the selectivity of these inhibitors, we conducted
      molecular dynamics simulations using protein-inhibitor modeling. We confirmed
      that ASP103 of Bcl-2 is a key residue and that hydrogen bonding between ASP103
      and ABT-199 confers the Bcl-2 selectivity of this inhibitor. For Bcl-XL
      selectivity, the secondary structure of alpha-helix 3 is a key factor. PHE105,
      SER106, and LEU108 in the loose alpha-helix 3 interact with A-1155463 to confer
      Bcl-XL selectivity. These findings provide important insights into the molecular
      mechanisms of selective inhibitors of Bcl-2 family proteins.

PMID- 29197726
TI  - The neural signature of self-concept development in adolescence: The role of
      domain and valence distinctions.
AB  - Neuroimaging studies in adults showed that cortical midline regions including
      medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important
      in self-evaluations. The goals of this study were to investigate the contribution
      of these regions to self-evaluations in late childhood, adolescence, and early
      adulthood, and to examine whether these differed per domain (academic, physical
      and prosocial) and valence (positive versus negative). Also, we tested whether
      this activation changes across adolescence. For this purpose, participants
      between ages 11-21-years (N = 150) evaluated themselves on trait sentences in an
      fMRI session. Behaviorally, adolescents rated their academic traits less
      positively than children and young adults. The neural analyses showed that
      evaluating self-traits versus a control condition was associated with increased
      activity in mPFC (domain-general effect), and positive traits were associated
      with increased activity in ventral mPFC (valence effect). Self-related mPFC
      activation increased linearly with age, but only for evaluating physical traits.
      Furthermore, an adolescent-specific decrease in striatum activation for positive
      self traits was found. Finally, we found domain-specific neural activity for
      evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC)
      domains. Together, these results highlight the importance of domain distinctions
      when studying self-concept development in late childhood, adolescence, and early
      adulthood.

PMID- 29197727
TI  - Development of face recognition: Dynamic causal modelling of MEG data.
AB  - Electrophysiological studies of adults indicate that brain activity is enhanced
      during viewing of repeated faces, at a latency of about 250 ms after the onset of
      the face (M250/N250). The present study aimed to determine if this effect was
      also present in preschool-aged children, whose brain activity was measured in a
      custom-sized pediatric MEG system. The results showed that, unlike adults, face
      repetition did not show any significant modulation of M250 amplitude in children;
      however children's M250 latencies were significantly faster for repeated than non
      repeated faces. Dynamic causal modelling (DCM) of the M250 in both age groups
      tested the effects of face repetition within the core face network including the
      occipital face area (OFA), the fusiform face area (FFA), and the superior
      temporal sulcus (STS). DCM revealed that repetition of identical faces altered
      both forward and backward connections in children and adults; however the
      modulations involved inputs to both FFA and OFA in adults but only to OFA in
      children. These findings suggest that the amplitude-insensitivity of the immature
      M250 may be due to a weaker connection between the FFA and lower visual areas.

PMID- 29197728
TI  - Disulfiram as a novel inactivator of Giardia lamblia triosephosphate isomerase
      with antigiardial potential.
AB  - Giardiasis, the infestation of the intestinal tract by Giardia lamblia, is one of
      the most prevalent parasitosis worldwide. Even though effective therapies exist
      for it, the problems associated with its use indicate that new therapeutic
      options are needed. It has been shown that disulfiram eradicates trophozoites in
      vitro and is effective in vivo in a murine model of giardiasis; disulfiram
      inactivation of carbamate kinase by chemical modification of an active site
      cysteine has been proposed as the drug mechanism of action. The triosephosphate
      isomerase from G. lamblia (GlTIM) has been proposed as a plausible target for the
      development of novel antigiardial pharmacotherapies, and chemical modification of
      its cysteine 222 (C222) by thiol-reactive compounds is evidenced to inactivate
      the enzyme. Since disulfiram is a cysteine modifying agent and GlTIM can be
      inactivated by modification of C222, in this work we tested the effect of
      disulfiram over the recombinant and trophozoite-endogenous GlTIM. The results
      show that disulfiram inactivates GlTIM by modification of its C222. The
      inactivation is species-specific since disulfiram does not affect the human
      homologue enzyme. Disulfiram inactivation induces only minor conformational
      changes in the enzyme, but substantially decreases its stability. Recombinant and
      endogenous GlTIM inactivates similarly, indicating that the recombinant protein
      resembles the natural enzyme. Disulfiram induces loss of trophozoites viability
      and inactivation of intracellular GlTIM at similar rates, suggesting that both
      processes may be related. It is plausible that the giardicidal effect of
      disulfiram involves the inactivation of more than a single enzyme, thus
      increasing its potential for repurposing it as an antigiardial drug.

PMID- 29197729
TI  - Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis,
      biological activity and SARs.
AB  - Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ)
      nucleus was an important scaffold for new chemotherapeutic drugs targeting
      microtubules. For wide-ranging SARs, a series of derivatives were synthesized
      through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31,
      the angular geometry and substituents at the 3 and 7 positions were varied to
      explore interactions inside the colchicine site of tubulin. Of the new compounds
      synthesized, potent cytotoxicity (low and sub-nanomolar GI50 values) was observed
      with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell
      lines. Neither compound 21 nor 24 induced significant cell death in normal human
      lymphocytes, suggesting that the compounds may be selectively active against
      cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and
      HeLa cell lines. With both compounds, induction of apoptosis was associated with
      dissipation of the mitochondrial transmembrane potential and production of
      reactive oxygen species, indicating that cells treated with the compounds
      followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis
      revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic
      proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly
      synthesized compounds demonstrate that active pyrroloquinolinone derivatives
      strongly bind in the colchicine site of beta-tubulin.

PMID- 29197730
TI  - Platanic acid: A new scaffold for the synthesis of cytotoxic agents.
AB  - Thirty-seven different derivatives (2-38) have been prepared from platanic acid,
      a natural occurring triterpenoid. Main emphasis was the introduction of several N
      containing functional groups such as amines, amides and oximes and their
      screening for cytotoxic activity employing several human tumor cell lines using
      SRB assays. In these SRB assays, nearly all compounds showed good cytotoxicity
      for these human tumor cell lines. Two compounds (17 and 38), however, were
      submitted to extended biological testing and investigated with respect to their
      mode of action using fluorescence microscopy and FACS analysis. Compound 17, a
      methyl (3beta, 20R) 3-acetyloxy-20-amino-30-norlupan-28-oate, induced apoptosis
      in A2780 ovarian carcinoma cells.

PMID- 29197731
TI  - Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives
      bearing the 1,8-naphthyridin-2-one moiety.
AB  - A series of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one
      moiety were synthesized, and evaluated for their antiproliferative activity
      against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine
      kinases (c-Met, Flt-3, PDGFR-beta, VEGFR-2, EGFR, and c-Kit) inhibitory
      activities in vitro. Most compounds showed moderate to excellent potency, with
      the most promising analogue 32 showing Flt-3/c-Met IC50 value of 1.16/1.92 nM.
      Structure-activity relationship studies indicated that the hydrogen atom served
      as R1 group was benefited to the potency, and mono-electron-withdrawing groups
      (mono-EWGs) on the phenyl ring (such as R3 = 4-F) showed a higher preference for
      antiproliferative activity.

PMID- 29197732
TI  - Inhibitory effects and structural insights for a novel series of coumarin-based
      compounds that selectively target human CA IX and CA XII carbonic anhydrases.
AB  - Coumarin derivatives are a peculiar class of inhibitors of the family of
      metalloenzymes carbonic anhydrases (CA, EC 4.2.1.1). Several coumarins display
      higher affinity and selectivity toward most relevant and druggable CA isoforms.
      By decorating the natural compound umbelliferone (1) we have identified a new
      series of coumarin-based compounds demonstrating high CA inhibitory effects with
      nanomolar affinity for hCA IX and hCA XII isoforms that were considered a target
      amenable to develop antitumor agents. The most active tested compounds proved to
      be potent inhibitors with Ki values equal to that of the well-known inhibitor
      acetazolamide (AAZ), that lacks selectivity over ubiquitous hCA I and hCA II. As
      suggested by docking studies the coumarins, that are lacking of the canonical
      metal binding groups, do not interact with Zinc ion within the catalytic site as
      found for classical sulfonamide type inhibitors of CAs. Thus, the studied
      inhibitors might possess a non-classical inhibitory mode of action preventing the
      carbon dioxide to entry into catalytic cavity and its conversion into bicarbonate
      ion. Specifically, the most active inhibitor of hCA XII compound 18i (Ki value of
      5.5 nM) and its supposed hydrolytic products could establish a web of H-bond
      interactions within the enzymatic cavity.

PMID- 29197734
TI  - Regio- and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids
      via 1,3-dipolar cycloaddition reactions: Cytotoxic activity and SAR studies.
AB  - A library of novel dispiro compounds containing oxindole-pyrrolo-carbazole hybrid
      frame works has been synthesized in a fully regio- and stereoselective fashion by
      the three-component 1,3-dipolar cycloaddition of azomethineylides generated in
      situ from the condensation of isatins and benzylamine with 2
      arylidene/heteroarylidene-2,3,4,9-tetrahydro-1H-carbazole-1-one. The structures
      of the compounds were established by FT-IR, 1H NMR, 13C NMR, X-ray diffraction
      and elemental analysis. The synthesized dispiro heterocycles have been screened
      for in vitro cytotoxic activity by MTT assay and displayed enviable growth
      inhibition on both the cancer cell lines i.e. breast cancer cell line MCF-7 and
      lung cancer cell line A-549. Morphological changes and apoptosis induction have
      been studied by inverted light microscopic, fluorescent microscopic techniques
      and by flow cytometry analyses. The preliminary structure activity relationships
      were also carried out. Data indicated that among dispiro-carbazole compounds,6
      chloro-4'-(thiophen-2-yl)-5'-phenyl-3,4-dihydrodispiro[carbazole-2,3'-pyrrolo
      2',3"-indole]-9(H)-1,2"-dione 7e could be exploited as a significant therapeutic
      drug against breast cancer as well as lung cancer cell proliferation.

PMID- 29197733
TI  - Synthesis and biological evaluation of some novel diastereoselective
      benzothiazole beta-lactam conjugates.
AB  - Highly diastereoselective synthesis of some novel benzothiazole-substituted beta
      lactam hybrids was achieved starting from (benzo[d]thiazol-2-yl)phenol as an
      available precursor. This is the first time (benzo[d]thiazol-2-yl)phenoxyacetic
      acid has been used as ketene source in synthesizing monocyclic 2-azetidinones.
      These compounds were evaluated for their antimicrobial activities against a large
      panel of Gram-positive and Gram-negative bacterial strains and moderate
      activities were encountered. Antimalarial data revealed that adding methoxyphenyl
      or ethoxyphenyl group on the beta-lactam ring makes compounds that are more
      potent. Moreover, hemolytic activity and mammalian cell toxicity survey of the
      compounds showed their potential as a medicine.

PMID- 29197735
TI  - Novel triazine dimers with potent antitrypanosomal activity.
AB  - Human African trypanosomiasis (HAT), also known as sleeping sickness is a
      parasitic disease transmitted by the bite of the 'Glossina' insect, commonly
      known as the tsetse fly. This disease affects mostly poor populations living in
      remote rural areas of Africa. Untreated, it is usually fatal. Currently, safe and
      effective treatments against this disease are lacking. Phenotypic screening of
      triazine non-nucleoside HIV-1 reverse transcriptase inhibitors (monomers)
      resulted in potent and selective antitrypanosomal compounds. This serendipitous
      discovery and the presence of dimers in many compounds active against these
      neglected tropical diseases prompted us to investigate antitrypanosomal activity
      of triazine dimers. Optimization of the triazine dimers resulted in 3,3'
      (((ethane-1,2-diylbis(azanediyl))bis(4-(mesityloxy)-1,3,5-triazine-6,2
      diyl))bis(azanediyl))dibenzonitrile (compound 38), a compound with very potent in
      vitro and moderate in vivo antitrypanosomal activity.

PMID- 29197737
TI  - Mid-infrared pulsed laser ultrasonic testing for carbon fiber reinforced
      plastics.
AB  - Laser ultrasonic testing (LUT) can realize contactless and instantaneous non
      destructive testing, but its signal-to-noise ratio must be improved in order to
      measure carbon fiber reinforced plastics (CFRPs). We have developed a mid
      infrared (mid-IR) laser source optimal for generating ultrasonic waves in CFRPs
      by using a wavelength conversion device based on an optical parametric
      oscillator. This paper reports a comparison of the ultrasonic generation behavior
      between the mid-IR laser and the Nd:YAG laser. The mid-IR laser generated a
      significantly larger ultrasonic amplitude in CFRP laminates than a conventional
      Nd:YAG laser. In addition, our study revealed that the surface epoxy matrix of
      CFRPs plays an important role in laser ultrasonic generation.

PMID- 29197736
TI  - Abnormal cortical neural synchrony during working memory in schizophrenia.
AB  - OBJECTIVE: To better understand the origins of working memory (WM) impairment in
      schizophrenia we investigated cortical oscillatory activity in people with
      schizophrenia (PSZ) while they performed a WM task requiring encoding,
      maintenance, and retrieval/manipulation processes of spatial information.
      METHODS: We examined time-frequency synchronous energy of cortical source signals
      that were derived from magnetoencephalography (MEG) localized to cortical regions
      using WM-related hemodynamic responses and individualized structural head-models.
      RESULTS: Compared to thirteen healthy controls (HC), twelve PSZ showed
      performance deficits regardless of WM-load or duration. During encoding, PSZ had
      early theta and delta event-related synchrony (ERS) deficits in prefrontal and
      visual cortices which worsened with greater memory load and predicted WM
      performance. During prolonged maintenance of material, PSZ showed deficient beta
      event-related desynchrony (ERD) in dorsolateral prefrontal, posterior parietal,
      and visual cortices. In retrieval, PSZ showed reduced delta/theta ERS in the
      anterior prefrontal and ventral visual cortices and diminished gamma ERS in the
      premotor and posterior parietal cortices. CONCLUSIONS: Although beta/gamma
      cortical neural oscillatory deficits for maintenance/retrieval are evident during
      WM, the abnormal prefrontal theta-frequency ERS for encoding is most predictive
      of poor WM in schizophrenia. SIGNIFICANCE: Time-frequency-spatial analysis
      identified process- and frequency-specific neural synchrony abnormalities
      underlying WM deficits in schizophrenia.

PMID- 29197738
TI  - Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with
      other second-generation antidepressants for major depressive disorder in adults:
      A systematic review and network meta-analysis.
AB  - BACKGROUND: Second-generation antidepressants dominate the medical management of
      major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are
      the latest therapeutic options approved for the treatment of MDD. This systematic
      review aims to compare the benefits and harms of vilazodone, levomilnacipran, and
      vortioxetine with one another and other second-generation antidepressants.
      METHODS: We searched electronic databases up to September 2017 and reviewed
      reference lists and pharmaceutical dossiers to detect published and unpublished
      studies. Two reviewers independently screened abstracts and full text articles,
      and rated the risk of bias of included studies. Randomized controlled trials
      (RCTs) and controlled observational studies including adult outpatients with MDD
      were eligible for inclusion. We conducted network meta-analyses on response to
      treatment using frequentist multivariate meta-analyses models. Placebo- and
      active-controlled trials were eligible for network meta-analyses. RESULTS: Twenty
      four studies met our inclusion criteria. Direct comparisons were limited to
      vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or
      venlafaxine XR (extended release). Results of head-to-head trials and network
      meta-analyses, overall, indicated similar efficacy among levomilnacipran,
      vilazodone, or vortioxetine and other second-generation antidepressants. Although
      rates of overall adverse events and discontinuation due to adverse events were
      similar, RCTs reported several differences in specific adverse events. For most
      outcomes the strength of evidence was low. LIMITATIONS: Limitations are the focus
      of literature searches on studies published in English, possible reporting
      biases, and general methodological limitations of network meta-analyses.
      CONCLUSIONS: Overall, the available evidence does not indicate greater benefits
      or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with
      other second-generation antidepressants.

PMID- 29197739
TI  - A meta-analysis of the use of probiotics to alleviate depressive symptoms.
AB  - INTRODUCTION: Some preclinical and clinical studies have demonstrated the
      positive impact of probiotic supplementation on depressive symptoms. This paper
      aims to provide an updated meta-analysis on the topic. METHODS: Using the
      keywords [probiotics OR gut OR microflora OR microbiome OR bacteria OR yeast OR
      yoghurt OR lactobacillus OR bifidobacterium] AND [mood OR depression OR MDD OR
      suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of
      the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR) and
      Cochrane Field for Complementary Medicine database yielded 917 papers published
      in English between 1-Jan-1960 and 1-June-2017. RESULTS: 10 clinical trials with a
      total of 1349 patients were reviewed, comparing the use of probiotics to placebo
      controls. There was no significant difference in mood between the treatment and
      placebo group post-intervention as the standardized mean difference (SMD) was 
      0.128 (95% CI -0.261 to 0.00463, P=0.059). A separate subgroup analysis of
      studies conducted in healthy versus depressed individuals found significant
      improvements in the moods of individuals with mild to moderate depressive
      symptoms (SMD -0.684, 95% CI -1.296 to -0.0712, P=0.029) and non-significant
      effects in healthy individuals (SMD -0.0999, 95% CI -0.235 to 0.0348, P=0.146).
      LIMITATIONS: Inter-study discrepancies with respect to probiotic dosing,
      bacterial strains and strain combinations limit the comparability of current
      clinical trials. Furthermore, majority of existing RCTs were conducted in healthy
      individuals, making it difficult to extrapolate the results to depressed
      individuals. CONCLUSION: Probiotic supplementation has an overall insignificant
      effect on mood. Future studies should be conducted on more patients with
      clinically diagnosed depression.

PMID- 29197741
TI  - Exploration about changes of IL-10, NF-kappaB and MMP-3 in a rat model of
      cervical spondylosis.
AB  - OBJECTIVES: To investigate the relationship and mechanism between IL-10, NF
      kappaB and MMP-3 in cervical degenerative disease induced by unbalanced dynamic
      and static forces in rats. METHODS: Sixty Sprague Dawley rats were randomized
      into test (n=45) and control (n=15) groups, which were randomly subdivided into
      three groups corresponding to one-month, three-month and six-month post
      operation. Test group included 10, 15, 20 rats at corresponding postoperative
      stage and control group had five rats at each time point. By excising
      cervicodorsal muscles and ligaments of rats to establish unbalanced dynamic and
      static rat model in test group. The expression of IL-10, NF-kappaB and MMP-3 in
      the intervertebral disc tissue samples of both test and control group rats were
      detected by immunohistochemistry at one-month, three-month and six-month post
      operation. The results were analyzed and compared among groups. RESULTS: Compared
      with the control group, the positive expression of IL-10 in test group was
      significantly higher at three-month (P<0.05). In the same model group, IL-10 was
      highest at one-month. Compared with the control group, NF-kB in test group was
      higher at one-month, three-month and six-month. In the same model group, NF-kB
      was the highest at one-month, followed by the time at three-month and six-month.
      And, compared with the control group, MMP-3 was significantly higher in test
      group at one-month (P<0.05). CONCLUSION: Cervical degeneration may accompanied
      with the changes of IL-10, NF-kappaB and MMP-3.

PMID- 29197742
TI  - Asparaginase inhibits the lectin pathway of complement activation.
AB  - Oncological treatment has been associated with an increased risk of infection,
      most often related to therapy-induced pancytopenia. However, limited research has
      been conducted on the effect of oncological therapy on the complement system,
      being part of the non-cellular innate immune system. This became the rationale
      for an observational clinical study (C2012) in which we have investigated the
      prevalence of transient complement defects. Once we had observed such defects, a
      correlation of the complement defects to specific clinical parameters or to
      specific therapeutic regimens was investigated. A prominent defect observed in
      C2012 was the inhibition of the lectin pathway (LP) of complement activation
      during the treatment of acute lymphoblastic leukemia (ALL), which we could
      directly associate to the use of asparaginase (ASNase). Ex-vivo experiments
      confirmed a direct dose-dependent inhibitory effect of ASNase on the LP
      functionality.

PMID- 29197740
TI  - Gene set enrichment analysis and expression pattern exploration implicate an
      involvement of neurodevelopmental processes in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BD) is a common and highly heritable disorder of
      mood. Genome-wide association studies (GWAS) have identified several independent
      susceptibility loci. In order to extract more biological information from GWAS
      data, multi-locus approaches represent powerful tools since they utilize
      knowledge about biological processes to integrate functional sets of genes at
      strongly to moderately associated loci. METHODS: We conducted gene set enrichment
      analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome
      pathways and 24,025 patients with BD and controls. RNA expression of implicated
      individual genes and gene sets were examined in post-mortem brains across
      lifespan. RESULTS: Two pathways showed a significant enrichment after correction
      for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6
      of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite
      out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most
      pathway genes showed peaks of RNA co-expression during fetal development and
      infancy and mapped to neocortical areas and parts of the limbic system.
      LIMITATIONS: Pathway associations were technically reproduced by two methods,
      although they were not formally replicated in independent samples. Gene
      expression was explored in controls but not in patients. CONCLUSIONS: Pathway
      analysis in large GWAS data of BD and follow-up of gene expression patterns in
      healthy brains provide support for an involvement of neurodevelopmental processes
      in the etiology of this neuropsychiatric disease. Future studies are required to
      further evaluate the relevance of the implicated genes on pathway functioning and
      clinical aspects of BD.

PMID- 29197743
TI  - Synthesis, biological evaluation and molecular docking studies of a new series of
      chalcones containing naphthalene moiety as anticancer agents.
AB  - A series of chalcones containing naphthalene moiety 4a-4p have been synthesized,
      characterized by 1H NMR and 13C NMR and evaluated for their in vitro anticancer
      activity. The majority of the screened compounds displayed potent anticancer
      activity against both HCT116 and HepG2 human cancer cell lines. Among the series,
      compound 4h with a diethylamino group at the para position of the phenyl ring
      exhibited the most potent anticancer activity against HCT116 and HepG2 cell lines
      with IC50 values of 1.20 +/- 0.07 and 1.02 +/- 0.04 MUM, respectively. The
      preliminary structure-activity relationship has been summarized. Tubulin
      polymerization experiments indicated that 4h effectively inhibited tubulin
      polymerization and flow cytometric assay revealed that 4h arrests HepG2 cells at
      the G2/M phase in a dose-dependent manner. Furthermore, molecular docking studies
      suggested that 4h binds to the colchicine binding site of tubulin.

PMID- 29197744
TI  - Transcriptional landscape of a RETC634Y-mutated iPSC and its CRISPR-corrected
      isogenic control reveals the putative role of EGR1 transcriptional program in the
      development of multiple endocrine neoplasia type 2A-associated cancers.
AB  - MEN2A is a hereditary cancer-predisposing syndrome that affects patients with
      germline RET mutations. The effects of this oncogenic tyrosine kinase in the
      context of primitive stem cells are not known. In order to study these events, we
      generated a MEN2A induced Pluripotent Stem Cell (iPSC) line from a patient with
      RET mutation and an isogenic counterpart by CRISPR-Cas9 correction of the
      mutation. Whole exome sequencing of iPSC before and after CRISPR-Cas9 genome
      edition revealed no major exonic off target effect of the CRISPR correction.
      However, an integrative differential gene expression analysis of iPSC with
      oncogenic RETC634Y and its gene-corrected iPSC with RETY634C as well as RETwt
      iPSCs revealed activation of the Early Growth Response 1 (EGR1) transcriptional
      program in RET-mutated iPSC, a pathway shown to be involved in RET-induced
      oncogenesis. These data constitute the first proof of concept of the feasibility
      of the use of an iPSC and its genome-corrected counterpart to unravel the
      molecular mechanisms underlying the development of the hereditary MEN2A cancer
      predisposing syndrome.

PMID- 29197745
TI  - Cancer chemoprevention revisited: Cytochrome P450 family 1B1 as a target in the
      tumor and the microenvironment.
AB  - Cancer chemoprevention is the use of synthetic, natural or biological agents to
      prevent or delay the development or progression of malignancies. Intriguingly,
      many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently
      proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family
      1B1 (CYP1B1), an enzyme overexpressed in a wide variety of tumors and associated
      with angiogenesis. In turn, pro-inflammatory cytokines were reported to boost
      CYP1B1 expression, suggesting a key role of CYP1B1 in a positive loop of
      inflammatory angiogenesis. Other well-known pro-tumorigenic activities of CYP1B1
      rely on metabolic bioactivation of xenobiotics and steroid hormones into their
      carcinogenic derivatives. In contrast to initial in vitro observations, in vivo
      studies demonstrated a protecting role against cancer for the other CYP1 family
      members (CYP1A1 and CYP1A2), suggesting that the specificity of CYP1 family
      inhibitors should be carefully taken into account for developing potential
      chemoprevention strategies. Recent studies also proposed a role of CYP1B1 in
      multiple cell types found within the tumor microenvironment, including
      fibroblasts, endothelial and immune cells. Overall, our review of the current
      literature suggests a positive loop between inflammatory cytokines and CYP1B1,
      which in turn may play a key role in cancer angiogenesis, acting on both cancer
      cells and the tumor microenvironment. Strategies aiming at specific CYP1B1
      inhibition in multiple cell types may translate into clinical chemoprevention and
      angioprevention approaches.

PMID- 29197746
TI  - Proton therapy for locally advanced breast cancer: A systematic review of the
      literature.
AB  - BACKGROUND: Radiation therapy plays a major role in the management of adjuvant
      breast cancer with nodal involvement, with an iatrogenic increase of cardio
      vascular risk. Photon therapy, even with intensity modulation, has the downsides
      of high mean heart dose and heterogeneous target coverage, particularly in the
      case of internal mammary irradiation. This systematic review of the literature
      aims to evaluate proton therapy in locally advanced breast cancer. MATERIAL AND
      METHODS: PubMed was searched for original full-text articles with the following
      search terms: "Proton Therapy" and "Breast Cancer". On-going trials were
      collected using the words "Breast Cancer" and "Protons". RESULTS: 13 articles met
      the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil
      Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a
      better target coverage than photons, even compared with intensity modulation
      radiation therapy (including static or rotational IMRT or tomotherapy). With
      proton therapy, volumes receiving 95% of the dose were around 98%, with low
      volumes receiving 105% of the dose. Proton therapy often decreased mean heart
      dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with
      conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy
      than with photon therapy. Cutaneous toxicity observed with double scattering is
      improved with PBS. CONCLUSION: Proton therapy reduces mean heart dose in breast
      cancer irradiation, probably reducing late cardio-vascular toxicity. Large
      clinical studies will likely confirm a clinical benefit of proton therapy.

PMID- 29197747
TI  - Soft chitosan microbeads scaffold for 3D functional neuronal networks.
AB  - The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons
      represents a pivotal step for the development of brain-on-a-chip experimental
      models to study neuronal (dys)functions and particularly neuronal connectivity.
      The use of hydrogel-based scaffolds for 3D cell cultures has been extensively
      studied in the last years. However, limited work on biomimetic 3D neuronal
      cultures has been carried out to date. In this respect, here we investigated the
      use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a
      microbead based 3D scaffold to be coupled to primary neuronal cells. CHI
      microbeads were characterized by optical and atomic force microscopies. The
      cell/scaffold interaction was deeply characterized by transmission electron
      microscopy and by immunocytochemistry using confocal microscopy. Finally, a
      preliminary electrophysiological characterization by micro-electrode arrays was
      carried out.

PMID- 29197748
TI  - Emergence of synthetic mRNA: In vitro synthesis of mRNA and its applications in
      regenerative medicine.
AB  - The field of gene therapy has evolved over the past two decades after the first
      introduction of nucleic acid drugs, such as plasmid DNA (pDNA). With the
      development of in vitro transcription (IVT) methods, synthetic mRNA has become an
      emerging class of gene therapy. IVT mRNA has several advantages over conventional
      pDNA for the expression of target proteins. mRNA does not require nuclear
      localization to mediate protein translation. The intracellular process for
      protein expression is much simpler and there is no potential risk of insertion
      mutagenesis. Having these advantages, the level of protein expression is far
      enhanced as comparable to that of viral expression systems. This makes IVT mRNA a
      powerful alternative gene expression system for various applications in
      regenerative medicine. In this review, we highlight the synthesis and preparation
      of IVT mRNA and its therapeutic applications. The article includes the design and
      preparation of IVT mRNA, chemical modification of IVT mRNA, and therapeutic
      applications of IVT mRNA in cellular reprogramming, stem cell engineering, and
      protein replacement therapy. Finally, future perspectives and challenges of IVT
      mRNA are discussed.

PMID- 29197749
TI  - Radiocesium uptake through leaf surfaces of tea plants (Camellia sinensis L.).
AB  - To clarify the source of radiocesium detected in newly emerged tea leaves
      contaminated just before the time of bud opening by fallout of radionuclides from
      Fukushima Dai-ichi Nuclear Power Plant, 137CsCl solution (0.185 M Bq mL-1) was
      applied to the front or the backside surfaces of mature leaves of tea plant
      (Camellia sinensis L. cv. Yabukita) at the time of bud opening. A 21 days after
      foliar application, the buds had grown and developed to the three- or four-leaf
      stage. In the front treatment, almost all (95%) of the applied 137Cs was present
      in the mature leaves (hot mother leaves). In the backside treatment, 68% of
      applied 137Cs also remained in hot mother leaves, but 22% and 10% was found in
      the new shoots attached to hot mother leaves and the other parts (non-applied
      mature leaves, stems and roots), respectively. The images of a hot leaf and its
      attached new shoots by imaging plate analysis revealed that the results coincided
      with those of the 137Cs distribution above. These suggested that radiocesium was
      primarily absorbed from the backside surface of tea leaves through the stoma, and
      then the greater part was transported to newly emerged tea organs during the new
      shoot growth period.

PMID- 29197750
TI  - Mechanical properties of bovine cortical bone based on the automated ball
      indentation technique and graphics processing method.
AB  - Cortical bone provides the main form of support in humans and other vertebrates
      against various forces. Thus, capturing its mechanical properties is important.
      In this study, the mechanical properties of cortical bone were investigated by
      using automated ball indentation and graphics processing at both the macroscopic
      and microstructural levels under dry conditions. First, all polished samples were
      photographed under a metallographic microscope, and the area ratio of the
      circumferential lamellae and osteons was calculated through the graphics
      processing method. Second, fully-computer-controlled automated ball indentation
      (ABI) tests were performed to explore the micro-mechanical properties of the
      cortical bone at room temperature and a constant indenter speed. The indentation
      defects were examined with a scanning electron microscope. Finally, the
      macroscopic mechanical properties of the cortical bone were estimated with the
      graphics processing method and mixture rule. Combining ABI and graphics
      processing proved to be an effective tool to obtaining the mechanical properties
      of the cortical bone, and the indenter size had a significant effect on the
      measurement. The methods presented in this paper provide an innovative approach
      to acquiring the macroscopic mechanical properties of cortical bone in a
      nondestructive manner.

PMID- 29197751
TI  - Dacron graft as replacement to dissected aorta: A three-dimensional fluid
      structure-interaction analysis.
AB  - Aortic dissection (AD) is a serious medical condition characterized by a tear in
      the intima, the inner layer of the aortic walls. In such occurrence, blood is
      being diverted to the media (middle) layer and may result in patient death if not
      quickly attended. In the case where the diseased portion of the aorta needs to be
      replaced, one common surgical technique is to use a graft made of Dacron, a
      synthetic fabric. We investigate the response of a composite human aortic segment
      Dacron graft structure subjected to blood flow using the three-dimensional fluid
      structure-interaction (FSI) capability in Abaqus. We obtain stress and strain
      profiles in each of the three layers of the aortic walls as well as in the Dacron
      graft. Results are compared when elastic and hyperelastic models are used and
      when isotropy vs. anisotropy is assumed. The more complex case (hyperelastic
      anisotropy) is represented by the Holzapfel-Gasser-Ogden (HGO) model which also
      accounts for the orientation of the fibers present in the tissues. The fluid flow
      is taken as Newtonian, incompressible, pulsatile and turbulent. The simulation
      show that for all the cases, the von Mises stress distribution at aorta-Dacron
      interface is well below the ultimate strength of the aorta. No significant change
      in radial displacement at the interface of the two materials due to blood flow is
      observed. Computation cost is also addressed and results show that the
      hyperelastic-anisotropic model takes about three times longer to run than the
      elastic isotropic case. Trade-off between accuracy and computational cost has to
      be weighted.

PMID- 29197752
TI  - Cognitive distortions in anorexia nervosa and borderline personality disorder.
AB  - Thought-shape fusion (TSF) is a cognitive distortion associated with eating
      disorders (ED). A similar distortion, thought-abandonment fusion (TAbF), is
      assumed to occur in borderline personality disorder (BPD). In this study the
      specificity of TSF in participants with anorexia nervosa (AN) and TAbF in
      participants with BPD was examined. 63 patients completed questionnaires
      assessing the manifestation of trait-TAbF and trait-TSF, as well as relevant
      psychopathology. Nonparametric conditional inference trees were used to test for
      cognitive disorder-specificity. Participants with AN exhibited higher trait-TSF
      scores than those with BPD, when participants with BPD and a co-occurring AN were
      removed. Trait-TSF in participants with AN seemed to be disorder-specific.
      Participants with BPD and a co-occurring AN had the highest TAbF-scores. The
      specificity hypothesis could only be partially confirmed for trait-TAbF: while
      participants with BPD and a co-occurring AN tended to have the highest trait-TAbF
      scores, high mean values could also be found in participants with AN. The results
      indicate that TAbF is not specific to BPD, but may also play a role in AN. Both
      distortions seem to play a role in the maintenance of the respective disorders.

PMID- 29197753
TI  - Longitudinal analysis of the impact of economic empowerment on risk for intimate
      partner violence among married women in rural Maharashtra, India.
AB  - The purpose of this study was to assess via longitudinal analysis whether women's
      economic empowerment and financial inclusion predicts incident IPV. This
      prospective study involved analysis of three waves of survey data collected from
      rural young married women (n = 853 women) in Maharashtra at baseline and 9&18
      month follow-ups. This study, which was in the field from 2012 to 2014, was
      conducted as part of a larger family planning evaluation study unrelated to
      economic empowerment. Participants were surveyed on economic empowerment, as
      measured by items on women's income generation and joint decision-making of
      husband's income, and financial inclusion, as measured by bank account ownership.
      Women's land ownership and participation in microloan programs were also assessed
      but were too rare (2-3% reporting) to be included in analyses. Longitudinal
      regression models assessed whether women's economic empowerment predicted
      incident IPV at follow-up. At Wave 1 (baseline), one in ten women reported IPV in
      the past six months; 23% reported income generation; 58% reported having their
      own money; 61% reported joint control over husband's money, and 10% reported bank
      ownership. Women's income generation and having their own money did not predict
      IPV over time. However, women maintaining joint control over their husband's
      income were at a 60% reduced risk for subsequent incident IPV (AOR = 0.40; 95% CI
      = 0.18, 0.90), and women gaining joint control over time were at a 70% reduced
      risk for subsequent incident IPV (AOR = 0.30; 95% CI = 0.13, 0.72), relative to
      women whose husbands maintained sole control over his income. Women who initiated
      a new bank account by Wave 3 also had a 56% reduced likelihood of reporting
      incident IPV in this same wave (AOR = 0.44; 95% CI = 0.22, 0.93), relative to
      those who maintained no bank account at Waves 1 and 3. These findings suggest
      that women's joint control over husband's income and her financial inclusion as
      indicated by bank ownership appear to reduce risk for IPV, whereas her income
      generation or control over her own income do not. Awareness of and participation
      in financial inclusion services may help reduce women's risk for IPV in rural
      India and elsewhere.

PMID- 29197754
TI  - Alcohol use by suicide victims in the city of Sao Paulo, Brazil, 2011-2015.
AB  - Excessive alcohol consumption is a serious public health issue, because
      drunkenness affects critical judgment and self-control which could trigger
      violent and self-harm behavior, with thus a potential association between alcohol
      consumption and suicide deaths. The objective of the present study was to assess
      the association between alcohol consumption and suicide deaths in the city of Sao
      Paulo, Brazil, from 2011 to 2015, and its relationship with socio-demographic
      characteristics of the victims and the circumstances of the suicide. A cross
      sectional retrospective study was conducted by collection of data from 1,700
      suicide victims subjected to examination of blood alcohol concentration (BAC)
      from toxicology reports from the Institute of Legal Medicine of the State of Sao
      Paulo, Brazil. Alcohol was detected in blood samples of 30.2% of the victims and
      mean BAC levels were 1.73 +/- 0.08 g/L. The mean age of the victims was 39.90 +/-
      0.75 years. The majority of the victims were male (74.6%) and the prevalence of
      positive BAC was higher amongst men (34.7%) than women (17.1%), p<0.05. The
      majority of the victims were white skinned (64.7%), but there was a higher
      proportion of victims with positive BAC among mulatto and black individuals,
      p<0.05. Hanging was the most prevalent suicide method in the sample (48.7%) and
      amongst men (55.4%), but amongst women it was jumping from a height (35%), p <
      0.05.

PMID- 29197755
TI  - Occurrence, removal and risk of organic micropollutants in wastewater treatment
      plants across China: Comparison of wastewater treatment processes.
AB  - This study investigated the occurrence, removal and risk of 42 organic
      micropollutants (MPs), including 30 pharmaceuticals and personal care products
      and 12 endocrine disrupting chemicals, in 14 municipal wastewater treatment
      plants (WWTPs) distributed across China. The composition profiles of different MP
      categories in the influent, effluent, and excess sludge were explored and the
      aqueous removal efficiencies of MPs were determined. Quantitative meta-analysis
      was performed to compare the efficacies of different wastewater treatment
      processes in eliminating MPs. Results indicate that different MP categories
      showed quite similar distributions among the studied WWTPs, with phenolic
      estrogenic compounds (PEs), macrolides, and fluoroquinolones being always
      dominant in the influent, effluent and excess sludge. Tetracyclines, bezafibrate,
      caffeine, steroid estrogens, and PEs showed high and stable aqueous removal
      efficiencies, whereas other MPs showed considerably varied aqueous removal
      efficiencies. Anaerobic/anoxic/oxic process combined with a moving-bed biofilm
      reactor achieved the highest aqueous removal of MPs among various secondary
      treatment processes. A combined process consisting of ultrafiltration, ozonation
      and ClO2 disinfection resulted in the highest removal of MPs among the tertiary
      treatment processes. Sulfamethoxazole, ofloxacin, ciprofloxacin, clarithromycin,
      erythromycin, estrone, and bisphenol A in the effluent, as well as beta-estradiol
      3-sulfate in the excess sludge could pose high risks. This study draws an overall
      picture about the current status of MPs in WWTPs across China and provides useful
      information for better control of the risks associated with MPs.

PMID- 29197756
TI  - Droplet distribution and airborne bacteria in an experimental shower unit.
AB  - Although human exposure to water aerosols is common in residential showers, the
      droplet distribution patterns generated in showers are not well understood nor is
      the bacteria released during shower operation. In this study, a two-phase flow
      Particle Tracking Velocimetry (PTV) algorithm was successfully used to
      characterize the spatial spray pattern and velocity field in two experimental
      showers (one low-flow and one high-flow). In addition, the airborne bacteria
      present in the shower over nearly 5 months of controlled operation was determined
      for both showers. The results indicate that the droplet velocity out of the low
      flow showerhead (which had fewer orifices) was significantly higher than that out
      of the high-flow showerhead resulting in a higher aerosol number concentration in
      the low-flow shower and more consistent wetting of the shower wall. Both
      showerheads generated droplets in the respirable range and genera of potential
      health concern were observed in the shower aerosols measured both prior to and
      following shower operation. The study provides one of the first visualizations of
      droplet spray patterns in residential showers and provides insight into the
      airborne bacteria present in showers.

PMID- 29197757
TI  - Primary sewage sludge filtration using biomass filter aids and subsequent
      hydrothermal co-liquefaction.
AB  - Hydrothermal liquefaction (HTL) is a promising technology for biofuel production
      and treatment of wastewater sludge. The current study investigates a novel
      utilization of biomass-assisted filtration of primary sludge to obtain high dry
      matter (DM) content sludge. Drastic improvements in filtration speed are achieved
      using different types of lignocellulosic biomass filter aids prepared via
      mechanical pre-treatment. The combined sludge-biomass filter cake is subsequently
      used as a feedstock for HTL and shows superior bio-crude yields and properties
      compared to their individual counterparts. The chemical energy recovery to bio
      crude is increased to 75% compared to 46% for biomass and 67% for sludge on its
      own. The increased DM content of filter cakes (~25%) compared to primary sludge
      (5%) increases the energy efficiency of HTL of primary sludge by a factor of 4.5.
      Introducing a biomass filteraid-HTL combination to a wastewater treatment plant
      would reduce the organic carbon load to treat by 62%. By combining sludge with
      lignocellulosic biomass the use of alkali catalyst can be avoided entirely which
      represents a major cost factor in HTL of lignocellulosics.

PMID- 29197758
TI  - UV-filters and musk fragrances in seafood commercialized in Europe Union:
      Occurrence, risk and exposure assessment.
AB  - In the framework of the FP7 ECsafeSeafood project, 62 seafood samples
      commercialized in Europe Union from several representative species - mackerel,
      tuna, salmon, seabream, cod, monkfish, crab, shrimp, octopus, perch and plaice -
      were analysed for residues of 21 personal care products (PCPs), including 11 UV
      filters (UV-Fs) and 10 musk fragrances (musks). PCPs analysis were performed by
      Quick, Easy, Cheap, Effective Rugged, Safe (QuEChERS), combined with liquid
      liquid extraction (LLE) or dispersive solid-phase extraction (dSPE), followed by
      gas chromatography-tandem mass spectrometry (GC-MS/MS). The results showed the
      presence in a wide range of samples of nine out of eleven UV-Fs compounds
      analysed, namely 2-ethylhexyl salicylate (EHS), 2-ethylhexyl,4-methoxycinnamate
      (EHMC), 4-methylbenzylidenecamphor (4-MBC), benzophenone-1 (BP1), benzophenone-3
      (BP3), isoamyl-4-methoxycinnamate (IMC), 2,2'-dihydroxy-4,4'
      dimethoxybenzophenone (DHMB), homosalate (HS), and octocrylene (OC), whereas
      galaxolide (HHCB), galaxolide lactone (HHCB-lactone), and tonalide (AHTN) were
      the most found musks. The potential risks to human health associated with the
      exposure to eight of the more prevalent PCPs - EHS, EHMC, 4-MBC, BP1, BP3, IMC,
      HHCB, and AHTN - through seafood consumption were assessed for consumers from
      five European countries (Belgium, Ireland, Italy, Portugal and Spain). Results
      showed that the human exposure to UV-Fs and musks estimated from the
      concentration values found in seafood and the daily consumption of concerned
      seafood species, were far below toxicological reference values.

PMID- 29197759
TI  - Source identification of human exposure to lead in nine Cree Nations from Quebec,
      Canada (Eeyou Istchee territory).
AB  - While policies to decrease lead in the environment have been implemented to
      reduce human exposure to various lead sources, the use of lead ammunition to
      harvest wild game may continue to contribute significantly to human blood lead
      levels (BLLs). As part of a multi-community environment-and-health study, BLLs
      representing all age groups were evaluated in the nine Cree Nations located in
      the James and Hudson Bay regions of Quebec, Canada. Personal, market food,
      traditional food and 24-h recall questionnaires were administered. Predictor
      variables were assessed for various exposure sources, including diet and hunting
      practices. Elevated BLLs were observed in association with increased hunting
      status, use of firearms and leaded ammunition, and consumption of traditional
      foods. Significant differences were observed between all communities, age groups
      and sexes. Recommendations include educational campaigns that promote switching
      to non-lead ammunition and, if lead ammunition continues to be used, careful
      removal from tissues of pellets, bullet fragments and ammunition paths.

PMID- 29197761
TI  - The interaction between drought and elevated CO2 in water relations in two
      grassland species is species-specific.
AB  - Climate change can have major consequences for grassland communities since the
      different species of the community utilize different mechanisms for adaptation to
      drought and elevated CO2 levels. In addition, contradictory data exist when the
      combined effects of elevated CO2 and drought are analyzed because the soil water
      content is not usually similar between CO2 concentrations. Thus, the objectives
      of this work have been to examine the effect of water stress on plant water
      relations in two grassland species (Trifolium pratense and Agrostis capillaris),
      analyzing the possible differences between the two species when soil water
      content is equal in all treatments, and to elucidate if development under
      elevated CO2 increases drought tolerance and if so, which are the underlying
      mechanisms. At ambient CO2, when soil volumetric water content was 15%, both
      species decreased their water potential in order to continue taking up water.
      Trifolium pratense performed osmotic adjustment, while Agrostis capillaris
      decreased the rigidity of its cell wall; moreover, both species increased the
      root to shoot ratio and decreased leaf area. However, these mechanisms were not
      sufficient to maintain cell turgor. Elevated CO2 partially mitigated the negative
      impact of drought on turgor potential in Trifolium pratense through a higher
      osmotic adjustment and root to shoot ratio and in Agrostis capillaris through a
      higher leaf relative water content caused by higher hydraulic conductance, but
      the impact of drought was not mitigated in either species by higher soil water
      conservation.

PMID- 29197760
TI  - Lifetime exposure to ambient air pollution and methylation of tumor suppressor
      genes in breast tumors.
AB  - BACKGROUND: We previously reported increased risk of breast cancer associated
      with early life exposure to two measures of air pollution exposure, total
      suspended particulates (TSP) and traffic emissions (TE), possible proxies for
      exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been
      shown to be associated with aberrant patterns of DNA methylation in peripheral
      blood of healthy individuals. Exposure to PAHs and methylation in breast tumor
      tissue has received little attention. We examined the association of early life
      exposure to TSP and TE with patterns of DNA methylation in breast tumors.
      METHODS: We conducted a study of women enrolled in the Western New York Exposures
      and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB,
      GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based
      pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and
      when she had her first child was estimated. TE exposure was modeled for each
      woman's residence at menarche, her first birth, and twenty and ten years prior to
      diagnosis. Unconditional logistic regression was employed to estimate odds ratios
      (OR) of having methylation greater than the median value, adjusting for age,
      secondhand smoke exposure before age 20, current smoking status, and estrogen
      receptor status. RESULTS: Exposure to higher TSP at a woman's first birth was
      associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23-0.99) and
      higher methylation of SYK (OR = 1.86, 95% CI: 1.03-3.35). TE at menarche was
      associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05-5.33). TE
      at first birth and ten years prior to diagnosis was associated with decreased
      methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26-0.89).
      Although these associations were nominally significant, none were significant
      after adjustment for multiple comparisons (p < 0.01). CONCLUSIONS: We observed
      suggestive evidence that exposure to ambient air pollution throughout life,
      measured as TSP and TE, may be associated with DNA methylation of some tumor
      suppressor genes in breast tumor tissue. Future studies with a larger sample size
      that assess methylation of more sites are warranted.

PMID- 29197762
TI  - Lamb loin tenderness is not associated with plasma indicators of pre-slaughter
      stress.
AB  - The purpose of this study was to test if associations exist between plasma
      indicators of acute and chronic stress and lamb loin Warner Bratzler Shear Force
      (WBSF). Blood was collected at exsanguination from 2877 lambs from the Meat and
      Livestock Genetic Research flock with a suite of indicators analysed. Loin (M.
      longissimus lumborum) WBSF was measured after 5days aging. Plasma indicators of
      stress did not relate to WBSF, however a positive association was found between
      WBSF and kill order, indicating that immediate pre-slaughter factors may be
      causing reduced tenderness in lamb. In addition, selection for decreased fat
      depth (PFAT) was associated with increased loin WSBF, indicating that genetic
      selection for increased carcass leanness is negatively affecting lamb loin
      tenderness.

PMID- 29197763
TI  - Carbon monoxide packaging shows the same color improvement for dark cutting beef
      as high oxygen packaging.
AB  - In this study, carbon monoxide (CO) modified atmosphere packaging (MAP) was used
      to increase redness (a*) and lightness (L*) values of dark cutting beef (ultimate
      pH (pHu)>=6.10), compared to normal pHu beef and intermediate pHu beef (pH: 5.40
      5.79; pH: 5.80-6.09, respectively) during 20 d chilled storage. Compared with
      HiOx-MAP, CO-MAP exhibited similar color improvement effects (increased L*, a*,
      b* values) for all pHu beef groupings. The metmyoglobin (MetMb) content was lower
      under CO-MAP than that of HiOx-MAP in normal pHu beef, but opposite effects were
      observed in dark, high pH beef. This result could not be explained by MetMb
      reducing ability (MRA) and lipid oxidation, as both parameters were higher in CO
      MAP beef than either normal or high pHu beef, compared with HiOx-MAP. In
      conclusion, CO-MAP was effective to maintain the cherry red color for dark
      cutting beef, but the color improvement mechanisms might be different with HiOx
      packaging methods.

PMID- 29197764
TI  - Impact of reducing nitrate/nitrite levels on the behavior of Salmonella
      Typhimurium and Listeria monocytogenes in French dry fermented sausages.
AB  - Salmonella and Listeria monocytogenes are two pathogenic bacteria that most
      frequently contaminate pork meat. In dry fermented sausages, several hurdles are
      used for controlling bacterial growth such as nitrite and salt addition. In
      Europe, practices consist of adding potassium nitrate (250ppm expressed as NaNO3)
      or a combination of nitrate/nitrite (150/150ppm expressed as NaNO3/NaNO2
      respectively). However, involvement of these additives in nitrosamine formation
      is a matter of concern. Consequently, a decrease in nitrite/nitrate amounts is
      proposed. The aim of this study was to evaluate the impact of reducing levels of
      these additives on Listeria and Salmonella behavior. Using challenge-tests, five
      trials were carried out by varying the concentration of nitrate and
      nitrate/nitrite. Results shown that nitrite is a relevant hurdle for control
      Salmonella and Listeria. At the end of drying, the most significant reductions of
      pathogens are obtained in sausages with nitrite added at the both tested
      concentrations (120 or 80ppm NaNO2).

PMID- 29197765
TI  - Physical quality attributes of male and female wild fallow deer (Dama dama)
      muscles.
AB  - Physical meat quality measurements were conducted on the longissimus thoracis et
      lumborum, biceps femoris, semimembranosus, semitendinosus, infraspinatus and
      supraspinatus muscles from male (n=6) and female (n=6) fallow deer (Dama dama)
      harvested in South Africa. Ultimate pH (pHu), drip loss, cooking loss and shear
      force values were influenced (p<=0.05) by muscle, but not gender. Mean pHu
      readings were 5.4-5.6 in the muscles with the two forequarter muscles having the
      highest readings, while drip loss, cooking loss and shear force values ranged
      from 1.3-1.6%, 29.4-36.1% and 31.3-61.9N, respectively. Muscle, however, had an
      effect (p<=0.05) on all the measured colour parameters (L*, a*, b*, chroma, hue
      angle), whereas gender only influenced (p<=0.05) the a* and chroma values in
      certain muscles. It can be concluded that the physical meat quality attributes of
      the fallow deer muscles compare favourably with that from other game species
      commonly consumed in South Africa.

PMID- 29197767
TI  - The effects of sodium chloride and PSE meat on restructured cured-smoked pork
      loin quality: A response surface methodology study.
AB  - The effects of the PSE meat proportion (0 to 100%) and sodium chloride contents
      (0 to 2%) on technological and saltiness of restructured cured-smoked pork loins
      were investigated by using response surface methodology (RSM). Lipid oxidation,
      pH values and reheating loss of the products were most affected by the proportion
      of PSE meat, while the salt concentration mainly affected the water activity,
      expressible moisture values, hardness, chewiness and sliceability of the
      products. Perception of the salt flavor increased with the addition of salt and
      proportion of PSE meat in the elaborated products, where the addition of 0.5%
      salt was considered as ideal by consumers. It was concluded that an amount close
      to 0.8% salt is required for satisfactory maintenance of the technological
      characteristics of the restructured cured-smoked pork loins, especially when PSE
      meat is used in the formulation.

PMID- 29197766
TI  - A sensometric approach to the development of mortadella with healthier fats.
AB  - The aim of this study was to evaluate the sensory characteristics of mortadellas
      with different fat contents using Descriptive Analysis (DA) and Check-all-that
      apply (CATA) questions and their relationship with overall liking (OL). Five
      mortadella samples were studied. Sample 1, containing 16% fat. Sample 2 was
      formulated with 8% fat. Samples 3 and 4 were prepared by replacing 50% fat by a
      pre-emulsion composed of fish, canola and olive oil. A commercial fat-reduced
      sample was also studied. The sensory characteristics of the samples were
      evaluated by DA. Besides, eighty-four consumers evaluated their OL using a 9
      point scale and answered the CATA questions. Replacement or reduction of fat
      caused changes in the sensory characteristics of the samples. Commercial
      mortadella was the most liked. CATA questions along with penalty analysis and
      partial least squares regression (PLSR) of dummy variables on the OL helped to
      identify the attributes to be changed in the mortadella formulations.

PMID- 29197768
TI  - Consumer sensory and hedonic perception of sheep meat coppa under blind and
      informed conditions.
AB  - The development of air-dried cured sheep meat products represents an interesting
      option to add value to the meat of adult animals. In this context, the aim of the
      present study was to evaluate consumer sensory and hedonic perception of sheep
      meat coppa, an innovative product. Four sheep meat coppa samples were formulated
      by varying smoking (smoked vs. non-smoked) and salt content (4.5% vs. 3.4%), and
      compared with two commercial samples of regular pork meat coppa. Samples were
      evaluated under blind or informed conditions by 202 consumers, who had to rate
      their liking and to answer a check-all-that-apply question. Sheep and pork meat
      coppa samples did not largely differ in their overall liking in both experimental
      conditions. Smoking and high salt content significantly increased consumers'
      hedonic perception of sheep meat coppa. The information included in the labels
      did not modify consumer hedonic perception but influenced their sensory
      description, particularly for the terms related to the type of meat used in their
      manufacture. Results indicate positive market opportunities for sheep meat coppa
      in the Brazilian market.

PMID- 29197769
TI  - Hydrothermal liquefaction of microalgae over transition metal supported TiO2
      catalyst.
AB  - Hydrothermal liquefaction (HTL) of microalgae Nannochloropsis (NAS) over various
      transition metal M/TiO2 (M = Fe, Co, Ni, Mo, and Mn) was investigated. Ni/TiO2
      was the most effective catalyst to improve the yield and quality of biocrude and
      the liquefaction conversion. Ni/TiO2 was characterized by XRD, XRF, and XPS. The
      research of Effect of reaction temperature on HTL of NAS over Ni/TiO2 suggested
      that 300  degrees C led to a maximum biocrude yield of 48.23% and the highest
      liquefaction conversion of 89.28%. Adding Ni/TiO2 catalyst reduced the viscosity
      and provided more light-fraction in biocrude while brought a slight increase in
      total acid number (TAN). Gas chromatography-mass spectrometry (GC-MS) analysis
      demonstrated that adding Ni/TiO2 considerably changed the composition of biocrude
      and the possible pathways were discussed. Reproduction test showed the Ni/TiO2
      has an excellent reproduction ability in HTL of NAS.

PMID- 29197770
TI  - Low pressure supercritical CO2 extraction of astaxanthin from Haematococcus
      pluvialis demonstrated on a microfluidic chip.
AB  - This study demonstrates the efficacy of low pressure supercritical CO2 extraction
      of astaxanthin from disrupted Haematococcus pluvialis. A microfluidic reactor was
      employed that enabled excellent control and allowed direct monitoring of the
      whole process at the single cell level, in real time. Astaxanthin extraction
      using ScCO2 achieved 92% recovery at 55  degrees C and 8 MPa applied over 15 h.
      With the addition of co-solvents, ethanol and olive oil, the extraction rates in
      both experiments were significantly improved reaching full recovery within a few
      minutes. Notably, for the ethanol case, the timescales of extraction process are
      reduced 1800-fold from 15 h to 30 s at 55  degrees C and 8 MPa, representing the
      fastest complete astaxanthin extraction at such low pressures.

PMID- 29197771
TI  - Formation, characteristics and microbial community of aerobic granular sludge in
      the presence of sulfadiazine at environmentally relevant concentrations.
AB  - The growing occurrence of antibiotics in water environment is causing increasing
      concern. To investigate the impact of frequently detected sulfadiazine on the
      formation of aerobic granular sludge, four sequencing batch reactors (SBRs) were
      set up with different environmentally relevant concentrations of sulfadiazine.
      Results showed that sulfadiazine pressure could lead to larger and more compact
      sludge particles and cause slight effect on reactor performance. Presence of
      sulfadiazine apparently increased the extracellular polymeric substances (EPS)
      secretion of microorganisms. Quantitative polymerase chain reaction (qPCR) showed
      that the abundances of sulfanilamide resistance genes in sludge increased with
      addition of sulfadiazine significantly. Phylogenetic Investigation of Communities
      by Reconstruction of Unobserved States (PICRUSt) was used to predict functional
      genes, results showed that sulfadiazine led to an increase of specific functional
      genes. Thereby, it concluded that microorganisms could change the community
      structure by acclimating of functional bacteria and antibiotic resistance species
      to adapt to the antibiotic stress.

PMID- 29197772
TI  - Exploring stress tolerance mechanism of evolved freshwater strain Chlorella sp.
      S30 under 30 g/L salt.
AB  - Enhancement of stress tolerance to high concentration of salt and CO2 is
      beneficial for CO2 capture by microalgae. Adaptive evolution was performed for
      improving the tolerance of a freshwater strain, Chlorella sp. AE10, to 30 g/L
      salt. A resulting strain denoted as Chlorella sp. S30 was obtained after 46
      cycles (138 days). The stress tolerance mechanism was analyzed by comparative
      transcriptomic analysis. Although the evolved strain could tolerate 30 g/L salt,
      high salinity caused loss to photosynthesis, oxidative phosphorylation, fatty
      acid biosynthesis and tyrosine metabolism. The related genes of antioxidant
      enzymes, CO2 fixation, amino acid biosynthesis, central carbon metabolism and ABC
      transporter proteins were up-regulated. Besides the up-regulation of several
      genes in Calvin-Benson cycle, they were also identified in C4 photosynthetic
      pathway and crassulacean acid metabolism pathway. They were essential for the
      survival and CO2 fixation of Chlorella sp. S30 under 30 g/L salt and 10% CO2.

PMID- 29197773
TI  - Enrichment and adaptation yield high anammox conversion rates under low
      temperatures.
AB  - This study compared two anammox sequencing batch reactors (SBR) for one year.
      SBRconstantT was kept at 30  degrees C while temperature in SBRloweringT was
      decreased step-wise from 30  degrees C to 20  degrees C and 15  degrees C
      followed by over 140 days at 12.5  degrees C and 10  degrees C. High retention of
      anammox bacteria (AnAOB) and minimization of competition with AnAOB were key. 5-L
      anoxic reactors with the same inoculum were fed synthetic influent containing
      25.9 mg NH4+-N/L and 34.1 mg NO2--N/L (no COD). Specific ammonium removal rates
      continuously increased in SBRconstantT, reaching 785 mg NH4+-N/gVSS/d, and were
      maintained in SBRloweringT, reaching 82.2 and 91.8 mg NH4+-N/gVSS/d at 12.5 and
      10  degrees C respectively. AnAOB enrichment (increasing hzsA and 16S rDNA gene
      concentrations) and adaptation (shift from Ca. Brocadia to Ca. Kuenenia in
      SBRloweringT) contributed to these high rates. Rapidly settling granules
      developed, with average diameters of 1.2 (SBRconstantT) and 1.6 mm
      (SBRloweringT). Results reinforce the potential of anammox for mainstream
      applications.

PMID- 29197774
TI  - Effect of ammonia on the active microbiome and metagenome from stable full-scale
      digesters.
AB  - Four full-scale anaerobic digesters with a long history of stable operation were
      characterized in terms of active microbiome and metagenome. Isotopic
      fractionation of biogas demonstrated that acetotrophy was rather prevalent in
      reactors operated at <3 gTAN L-1 while hydrogenotrophy was predominant at >6 gTAN
      L-1, suggesting that syntrophic acetate oxidizing bacteria (SAOB) played a
      significant role in the latter. These results were generally coherent with the
      observed active bacterial and archaeal communities but no known SAOB were
      observed. Metagenome descriptions yielded 73 assembled population genomes, of
      which only 7 could be assigned at the species level. Gene annotation and
      association to relevant metabolic pathways indicated that the phyla Chloroflexi
      and Bacteroidales might encompass new, currently undescribed, SAOB/formate
      producing species that would metabolize acetate via the glycine cleavage system.
      The predominant hydrogenotrophic counterpart at a high ammonia content belonged
      to the genus Methanoculleus, which could also grow on acetate to a certain
      extent.

PMID- 29197775
TI  - Waste-to-biofuel integrated system and its comprehensive techno-economic
      assessment in wastewater treatment plants.
AB  - Combining wastewater treatment and biofuel production is considered the cost
      effective way for better waste remediation and lowering the environmental impact
      for biofuel production. In this study, an innovative integrated system
      incorporating sludge, scum and centrate treatment and biofuel production was
      developed. A comprehensive techno-economic analysis was conducted to evaluate the
      technology and economic feasibility of the integrated system with the
      consideration of biofuel production, wastewater treatment improvement, tax
      credits, carbon credit, and coproducts utilization. Benefited from the integrated
      system that the intermediate byproducts can be used in between the sub-systems,
      such as the glycerol generated from the scum-to-biodiesel production can be used
      as an organic carbon for the centrate-to-algae production, the estimated
      breakeven selling price of the bio-oil ($1.85/gallon) is very close to the 5-year
      averaged crude oil price. The assessment result showed the payback period and the
      IRRs of the integrated system are superior in comparison with others.

PMID- 29197776
TI  - Ultrafast fractionation of lignocellulosic biomass by microwave-assisted deep
      eutectic solvent pretreatment.
AB  - Deep eutectic solvents (DESs) have received increasing attention in recent years
      as designer solvents for bioprocessing. In this study, ultrafast microwave
      assisted DES pretreatment was developed for lignocellulose fractionation. The
      pretreatment was conducted for 45 s with microwave irradiation at 800 W using a
      DES composed of choline chloride and lactic acid (ChCl: LA). The results
      indicated that such pretreatment was highly effective in removing lignin and
      xylan while retaining most of cellulose in the pretreated solids. The ultrafast
      fractionation increased the cellulose digestibility by 2-5 folds. Switchgrass
      gave a similar glucose yield to corn stover but experienced less cellulose loss
      during the pretreatment. Miscanthus was also substantially fractionated but
      showed lower digestibility than switchgrass and corn stover. Lignin was readily
      recoverable with relatively high purity from all the pretreatment liquor. Our
      study demonstrated an innovative ultrafast pretreatment process with superior
      effectiveness for biomass fractionation and cellulose digestibility improvement
      as well as lignin extraction.

PMID- 29197777
TI  - Screening and comparative metabolic profiling of high lipid content microalgae
      strains for application in wastewater treatment.
AB  - New strains of green microalgae were isolated and screened for growth and the
      production of lipids from municipal wastewater. It was shown that the strain
      Micractinium sp. IC-76 has a biomass productivity of 37.18 +/- 4.12 mg L-1 d-1
      and a lipid content of 36.29 +/- 0.11%, with a total content of saturated and
      monounsaturated fatty acids of 71.9%. The efficiency of nitrogen (N-NH4) and
      phosphorus (P-PO4) removal was 96.4 +/- 0.7 and 77.8 +/- 5.6%, respectively. The
      metabolic differences at the exponential and stationary phases of growth between
      the closely related strains with different patterns of lipid accumulation were
      revealed via gas chromatography mass spectrometry metabolic profiling. The strain
      Micractinium sp. IC-76 in the stationary phase of growth shows a significant
      difference in carbohydrate metabolism, especially sucrose concentration. High
      lipid induction during cultivation in wastewater was also driven by changes in
      the biosynthesis of amino acids, fatty acids and the tricarboxylic acid cycle.

PMID- 29197778
TI  - Recovery of mixed volatile fatty acids from anaerobically fermented organic
      wastes by vapor permeation membrane contactors.
AB  - Volatile fatty acids (VFAs) are attractive compounds in renewable based bio
      refinery industries and can be produced through anaerobic digestion of organic
      wastes. Nevertheless, the recovery of VFAs from anaerobically digested organic
      wastes is the bottleneck of the resource recovery. In this study, VFA recovery
      from synthetic VFA solutions and fermented organic wastes via air-filled and
      tertiary amine extractant-filled PTFE membranes through vapor pressure membrane
      contactors (VPMC) was investigated. Acetic acid was recovered with greater than
      45% efficiency in all the fermented wastes. Recovery of propionic, butyric,
      valeric, and caproic acids through trioctylamine-filled PTFE membrane was greater
      than 86% and 95% from landfill leachate and fermentation broth of anaerobically
      digested organic waste, respectively. This study reveals that VFA separation can
      be effectively achieved via economic and environmental friendly VPMC system and
      the process is implementable as it can be coupled to a fermentation process to
      prevent inhibition and to recover VFAs.

PMID- 29197779
TI  - Model predictive control coupled with economic and environmental constraints for
      optimum algal production.
AB  - Algae production process is a key cost center in production of
      biofuels/bioproducts from microalgae. Decline in the growth of algae in outdoor
      ponds during non-optimal conditions is one of the hurdles for achieving
      consistently high algal production rates. An optimal controller can be used to
      overcome this limitation and provide reliable growth in outdoor conditions. A
      model predictive controller (MPC) was developed to optimize the algal growth,
      predicted by flux balance analysis, under natural disturbances, embedding within
      the cost function, the economic and environmental constraints associated with the
      process. The model, developed in MATLAB, was validated on a 30-L continuous algal
      culture under light, temperature and a combination of light and temperature
      disturbances. The MPC proved effective in minimization of a decrease in growth
      under these natural disturbances. The growth rates with MPC were observed to be
      79-116% higher as compared to the non-MPC growth.

PMID- 29197780
TI  - Characterization of an aerobic denitrifier Pseudomonas stutzeri strain XL-2 to
      achieve efficient nitrate removal.
AB  - An aerobic denitrifier was newly isolated and identified as Pseudomonas stutzeri
      strain XL-2. Strain XL-2 removed 97.9% of nitrate with an initial concentration
      about 100 mg/L. Nitrogen balance indicates that 12.4% of the initial nitrogen was
      converted to N2O, and 62.4% was converted to N2. Single factor experiments
      indicate that the optimal conditions for nitrate removal were C/N ratio of 10,
      temperature of 30  degrees C and shaking speed of 120 rpm. Sequence amplification
      indicates that the denitrification genes of napA, nirS, norB and nosZ were
      present in strain XL-2. Combined with nitrogen balance, strain XL-2 presents the
      metabolic pathway of NO3- -> NO2- -> NO  ->  N2O -> N2 under aerobic conditions.
      The expression of napA and nirS might be responsible for the tolerance of
      dissolved oxygen by strain XL-2 during denitrification process.

PMID- 29197781
TI  - Which tasks measure what? Reflections on executive function development and a
      commentary on Podjarny, Kamawar, and Andrews (2017).
AB  - This article provides a selective review of the literature on executive function
      development and related topics, focusing on the conceptual and terminological
      confusions that might hinder communication among researchers in the field. The
      distinctions between working memory and updating, and between shifting and
      flexibility, are discussed. Methodological problems, which have implications
      regarding whether a certain task can be considered a measure of a psychological
      construct, are also discussed. Research on preschoolers is examined with
      particular attention because it is a rapidly growing but controversial field that
      seems in particular need of greater conceptual clarity. As a specific touchstone
      case, we discuss whether the Multidimensional Card Selection Task (MCST) created
      by Podjarny, Kamawar, and Andrews (2017) should better be considered a measure of
      concurrent cognitive flexibility or working memory capacity. It is argued that
      connecting tasks to theoretical constructs is not warranted unless based on
      rigorous empirical testing of well-formulated models.

PMID- 29197782
TI  - Language-minority children's sensitivity to the semantic relations between words.
AB  - The purpose of this study was to examine automatic language processing among
      Spanish-speaking language-minority children. A sample of 73 children (mean age =
      90.4 months) completed two measures of semantic priming: an auditory lexical
      decision task and a looking-while-listening task. It was hypothesized that within
      and cross-language semantic priming effects would occur but that translation
      priming effects would not occur. Results from vocabulary assessments indicated
      that language-minority children in this study were more proficient in English
      than they were in Spanish. Limited evidence for semantic priming effects within
      English and from English to Spanish emerged. In addition, substantial evidence
      for translation priming from Spanish to English and from English to Spanish
      emerged. Given the lack of within-Spanish semantic priming effects and the
      presence of translation priming effects from Spanish to English, the results of
      this study indicated that Spanish-speaking language-minority children rely on
      translation from their less proficient language to their more proficient language
      to access meaning. There was partial evidence that language-minority children's
      two languages are active simultaneously, indicating that early in life children
      develop semantic knowledge that is associated with words known in both languages.

PMID- 29197783
TI  - Lotus tetragonolobus and Maackia amurensis lectins influence phospho
      IkappaBalpha, IL-8, Lewis b and H type 1 glycoforms levels in H. pylori infected
      CRL-1739 gastric cancer cells.
AB  - PURPOSE: Attachment of Helicobacter pylori to the mucous epithelial cells and the
      mucous layer is said to be a crucial step for infection development. Sugar
      antigens of gastric mucins (MUC5AC, MUC1) can act as receptors for bacterial
      adhesins. The aim of the study was to investigate if Lotus tetragonolobus and
      Maackia amurensis lectins influence the level of MUC1, MUC5AC, Lewis b, H type 1,
      sialyl Lewis x, phospho-IkappaBalpha and interleukin 8 in Helicobacter pylori
      infected gastric cancer cells. MATERIALS AND METHODS: The study was performed
      with one clinical H. pylori strain and CRL-1739 gastric cancer cells. To assess
      the levels of mentioned factors immunosorbent ELISA assays were used. RESULTS:
      Coculture of cells with bacteria had no clear effect on almost all examined
      structures. After coculture with H. pylori and lectins, a decrease of the level
      of both mucins, Lewis b and H type 1 antigens was observed. Lectins addition had
      no effect on sialyl Lewis x. Maackia amurensis caused slight increase of phospho
      IkappaBalpha while interleukin 8 level was decreased. CONCLUSIONS: Lotus
      tetragonolobus and Maackia amurensis lectins can mediate in binding of
      Helicobacter pylori to gastric epithelium.

PMID- 29197784
TI  - Simulated photoperiod influences testicular activity in quail via modulating
      local GnRHR-GnIHR, GH-R, Cnx-43 and 14-3-3.
AB  - The hypothalamo-hypophyseal-gonadal axis mediated differential photosexual
      responses in quail kept under different simulated photoperiodic conditions have
      been studied in details. Local testicular GnRH-GnIH and their receptor system has
      been hypothesized to be modulated in quail showing different photo-sexual
      responses and thus influence the testicular activity and steroidogenesis through
      local (paracrine and autocrine) action. To validate this hypothesis, we studied
      the expression of gonadotropin releasing hormone receptor (GnRH-R), gonadotropin
      inhibiting hormone receptor (GnIH-R) mRNA, growth hormone receptor (GH-R),
      proliferating cell nuclear antigen (PCNA), 14-3-3, Connexin-43 (Cnx-43),
      steroidogenic factor-1 (SF-1), Steroidogenic Acute Regulatory protein (StAR),
      steroidogenic enzyme (3beta HSD) in testis as well as androgen receptor (AR) in
      testis and epididymis of photosensitive (PS), scotorefractory (SR),
      photorefractory (PR) and scotosensitive (SS) quail. Experimental findings clearly
      indicate the increased expression of GnIH-R mRNA and suppression of GnRH-R, GH-R,
      PCNA, 14-3-3, Connexin-43, SF-1, StAR, 3beta HSD in testis as well as AR in
      testis and epididymis of PR and SS quail, while PS and SR quail exhibited the
      opposite results i.e., significantly decreased expression of GnIH-R mRNA and
      increased expression of GnRH-R, GH-R, PCNA, 14-3-3, Cnx-43, SF-1, StAR, 3beta HSD
      in testis as well as AR in testis and epididymis. The significantly increased
      intra-testicular testosterone has been observed in the PS and SR quail while, PR
      and SS quail showed opposite results. Hence, we conclude that PS and SR quail
      showed significantly increased testicular activity and steroidogenesis while
      opposite pattern was observed in PR and SS quail.

PMID- 29197785
TI  - Impact of gingivitis treatment for diabetic patients on quality of life related
      to periodontal objective parameters: A randomized controlled clinical trial.
AB  - OBJECTIVES: Patients with diabetes have a poor oral health-related quality of
      life (OHRQoL). It is not clear if this situation could be changed with effective
      periodontal treatment. This study examined both patients with diabetes and
      systemically healthy individuals to discover the impact of a gingivitis treatment
      protocol on OHRQoL and its relation to objective periodontal parameters. DESIGN:
      After ultrasonic debridement, patients were randomly assigned to an essential
      oils (EO) or placebo mouthwash group. At baseline and 3 months, OHRQoL was
      assessed with the Oral Health and Quality of Life-United Kingdom questionnaire
      (OHQoL-UK) along with clinical, halitometric, microbiological and inflammatory
      objective parameters. The primary outcome was a change in OHQoL-UK scores. A
      factor analysis was performed and the impact of the extracted quality of life
      factor (QLF) and its interactions with diabetes, treatment, and time on the
      objective parameters, were tested by multiple linear regression models (p <
      0.05). Chi-Square test compared questionnaire-answering profiles (p<0.05).
      RESULTS: Combined treatment with EO provided OHQoL improvements in both systemic
      conditions. Positive effect of oral health status on quality of life increased in
      EO groups but not in placebo groups. Question I (self-confidence) showed the
      greatest factorial weight, while Question A (food intake) showed the lowest
      factorial weight. All patients who showed OHRQoL improvements and used the EO
      rinse showed the lowest plaque and gingival indices and lower levels of bacteria
      and volatile sulfur compounds. CONCLUSIONS: OHRQoL positively changed overtime.
      Most effective treatment protocols would provide better improvements in OHRQoL
      which is related to periodontal objective measures.

PMID- 29197786
TI  - Reliability and validity of the Bristol Breastfeeding Assessment Tool in the
      Turkish population.
AB  - BACKGROUND: breast milk is a natural source of nourishment, with a high level of
      bioefficacy that is easily digestible, easy to deliver, providing all the fluids,
      energy and nutrients that are needed for the optimum growth and development of a
      newborn. OBJECTIVE: this research aims to conduct a reliability and validity
      study of the Bristol Breastfeeding Assessment Tool (BBAT) in the Turkish
      population. DESIGN: the research was conducted in methodological design. SETTING:
      the Child Health Follow-up Polyclinic of a university hospital in Istanbul.
      PARTICIPANTS: the participants were 217 breastfed infants and their mothers.
      FINDINGS: the internal consistency of the Turkish version of Breastfeeding
      Assessment Tool (Cronbach's alpha = 0.77) and the intraclass correlation level
      are high (ICC = 0.89). Breastfeeding Assessment Tool displayed a high correlation
      with LATCH (Latch Audible, Swallowing, Type of Nipple, Comfort of Breast/Nipple,
      H-Hold/Position) (Pearson r = 0.76; p = 0.000). CONCLUSIONS: Breastfeeding
      Assessment Tool was successfully adapted into Turkish as a reliable and valid
      breastfeeding assessment tool that can be quickly and easily administered, and it
      was shown that the instrument could be readily adapted into other languages as
      well. IMPLICATIONS FOR PRACTICE: the Turkish version of Breastfeeding Assessment
      Tool is now available to Turkish midwives and nurses, who will be able to employ
      an instrument for breastfeeding assessment that has been proven effective. More
      studies are needed to demonstrate the efficacy of the instrument.

PMID- 29197787
TI  - The Midwifery services framework: What is it, and why is it needed?
AB  - Most low- and middle-income countries failed to meet the Millennium Development
      Goal targets for maternal, newborn and child health, and even more ambitious
      targets have been set under the Sustainable Development Goals and the Ending
      Preventable Maternal Mortality initiative. This means that many countries will
      need to accelerate progress on sexual, reproductive, maternal and newborn health
      over the next few years. Recent years have seen the publication of a large and
      convincing body of evidence about the potential of midwifery to make a
      significant contribution to this acceleration, but little practical guidance has
      emerged to help countries invest in midwifery services so that their health
      systems can meet the increasing need for sexual, reproductive, maternal and
      newborn health care. To help fill this gap, the International Confederation of
      Midwives designed and launched the Midwifery Services Framework, a new tool to
      guide countries through the process of strengthening and developing their
      midwifery services. This first of a series of three papers introduces the MSF,
      explains why it is needed, how it was developed, its guiding principles and its
      anticipated outcomes and impact. The other two papers explain the process of
      implementing the Midwifery Services Framework, and lessons learned in the first
      countries to start implementation.

PMID- 29197788
TI  - Effects of antagonistic and synergistic muscles' co-activation on mechanics of
      activated spastic semitendinosus in children with cerebral palsy.
AB  - OBJECTIVES: Most activities involve co-activation of several muscles and
      epimuscular myofascial force transmission (EMFT) can affect their mechanics. This
      can be relevant for spastic muscles of cerebral palsy (CP) patients. Isometric
      spastic semitendinosus (ST) forces vs. knee angle (KA-FST) data were collected
      intra-operatively to test the following hypotheses: (i) Inter-antagonistic EMFT
      elevates FST, (ii) changes the shape of KA-FST characteristics, (iii) reduces the
      muscle's joint range of force exertion (Range-FST) and (iv) combined inter
      antagonistic and synergistic EMFT further changes those effects. METHODS: 11
      limbs of 6 patients with CP (mean (SD) = 7.7 (4.7) years; GMFCS levels = II-IV)
      were tested in 3 conditions from 120 degrees  to full extension: ST activated (I)
      exclusively, (II) simultaneously with an antagonist, and (III) with added
      activation of synergists. RESULTS: Condition II increased FST (e.g., peak force =
      87.6 N (30.5 N)) significantly (by 33.6%), but condition III caused no further
      change. No condition changed the muscle's wide Range-FST (100.7 degrees  (15.9
      degrees )) significantly. Therefore, only the first hypothesis was confirmed.
      CONCLUSIONS: Co-activating its antagonist elevates forces of activated spastic ST
      substantially, but does not change its joint range of force exertion. Added
      activation of its synergists causes no further effects. Therefore, EMFT effects
      in CP can be relevant and need to be tested in other knee flexors.

PMID- 29197789
TI  - Nanostructured lipid carriers for improved oral delivery and prolonged
      antihyperlipidemic effect of simvastatin.
AB  - The purpose of the current study is to develop nanostructured lipid carriers
      (NLCs) for the delivery of the antihyperlipidemic drug simvastatin (SIM) to
      increase its extremely low oral bioavailability (<5%) and prolong its
      antihyperlipidemic effect. NLCs were prepared via emulsification-solvent
      evaporation technique followed by ultrasonication, and the effect of composition
      of the nanocarriers on the particle size, size distribution, surface charge,
      entrapment efficiency, drug release kinetics and physical stability was
      extensively studied. NLCs exhibited nanosized (<200nm) spherical morphologies
      with narrow size distribution and high drug entrapment efficiency (>75%),
      sustained drug release pattern, and negative surface charge (zeta potential of 
      35-40mV) that imparts sufficient electrostatic physical stability. When tested in
      vivo, SIM-NLCs of the optimal composition demonstrated improved and prolonged
      reduction in the total cholesterol and non-high density lipoprotein cholesterol
      levels, as compared to the drug suspension. After oral administration of a single
      dose of SIM-NLC, 4-fold increase in bioavailability was observed, as compared to
      the SIM suspension. Hence, NLCs might provide efficient nanodevices for the
      management of hyperlipidemia and promising drug delivery systems to enhance SIM
      oral bioavailability.

PMID- 29197790
TI  - Increase in volatilization of organic compounds using air sparging through
      addition in alcohol in a soil-water system.
AB  - This study developed a novel method to promote the remediation efficiency of air
      sparging. According to the enhanced-volatilization theory presented in this
      study, selected alcohols added to groundwater can highly enhance the
      volatilization amounts of organic compounds with high Henry's law constants. In
      this study, the target organic compounds consisted of n-hexane, n-heptane,
      benzene, toluene, 1,1,2-trichloroethane, and tetrachloroethene. n-pentanol, n
      hexanol, and n-heptanol were used to examine the changes in the volatilization
      amounts of organic compounds in the given period. Two types of soils with high
      and low organic matter were applied to evaluate the transport of organic
      compounds in the soil-water system. The volatilization amounts of the organic
      compounds increased with increasing alcohol concentrations. The volatilization
      amounts of the test organic compounds exhibited a decreasing order: n-heptanol>n
      hexanol>n-pentanol. When 10mg/L n-heptanol was added to the system, the maximum
      volatilization enhancement rate was 18-fold higher than that in distilled water.
      Samples of soil with high organic matter might reduce the volatilization amounts
      by a factor of 5-10. In the present study, the optimal removal efficiency for
      aromatic compounds was approximately 98%.

PMID- 29197791
TI  - Roles of different active metal-reducing bacteria in arsenic release from arsenic
      contaminated paddy soil amended with biochar.
AB  - Although biochar has great potential for heavy metal removal from sediments or
      soils, its impact on arsenic biogeochemistry in contaminated paddy fields remains
      poorly characterized. In this study, anaerobic microcosms were established with
      arsenic-contaminated paddy soil to investigate arsenic transformation as well as
      the potentially active microbial community and their transcriptional activities
      in the presence of biochar. The results demonstrated that biochar can
      simultaneously stimulate microbial reduction of As(V) and Fe(III), releasing high
      levels of As(III) into the soil solution relative to the control. Total RNAs were
      extracted to profile the potentially active microbial communities, which
      suggested that biochar increased the abundance of arsenic- and iron-related
      bacteria, such as Geobacter, Anaeromyxobacter and Clostridium compared to the
      control. Reverse transcription, quantitative PCR (RT-qPCR) showed that the
      abundance of Geobacter transcripts were significantly stimulated by biochar
      throughout the incubation. Furthermore, significant positive correlations were
      observed between the abundance of Geobacter transcripts and As(V) concentrations,
      and between that of Clostridium transcripts and Fe(III) concentrations in biochar
      amended microcosms. Our findings suggest that biochar can stimulate the activity
      of metal-reducing bacteria to promote arsenic mobility. The Geobacter may
      contribute to As(V) reduction in the presence of biochar, while Clostridium has a
      role in Fe(III) reduction.

PMID- 29197792
TI  - New insight into PM2.5 pollution patterns in Beijing based on one-year
      measurement of chemical compositions.
AB  - In recent years, air pollution has become a major concern in China, especially in
      the capital city of Beijing. Haze events occur in Beijing over all four seasons,
      exhibiting distinct characteristics. In this study, the typical evolution
      patterns of atmospheric particulate matter with a diameter of less than 2.5MUm
      (PM2.5) in each season were illustrated by episode-based analysis. In addition, a
      novel method was developed to elucidate the driving species of pollution, which
      is the largest contributor to the incremental PM2.5 (DeltaPM2.5), not PM2.5. This
      method revealed a temporal variation of the driving species throughout the year:
      nitrate-driven spring, sulfate-driven summer, nitrate-driven early fall, and
      organic matters (OM)-driven late fall and winter. These results suggested that
      primary organic particles or volatile organic compounds emissions were dominant
      in the heating season due to residential heating, while NOx and SO2 emissions
      dominated in the other seasons. Besides, nitrate formation seemed more
      significant than sulfate formation during severe pollution episodes. It was also
      found that the pollution formation mechanism in the winter showed some unique
      features in comparison with the other seasons: aqueous reactions were more
      important in the winter, while multiple pathways coexisted in the other seasons.
      Furthermore, this study confirmed that the PM2.5 in Beijing was moderately acidic
      despite a fully neutralized system. In addition, the acidity variation during
      pollution episodes displayed different patterns between seasons and was driven by
      both the variation of aerosol water and chemical compositions. These results
      provide a new perspective to understand the characteristics and mechanisms of
      aerosol pollution in Beijing. However, more accurate measurements are necessary
      for effective air pollution control that depends on the seasonal variation of
      fine particle formation in Beijing and the surrounding areas.

PMID- 29197793
TI  - Native-plant amendments and topsoil addition enhance soil function in post-mining
      arid grasslands.
AB  - One of the most critical challenges faced in restoration of disturbed arid lands
      is the limited availability of topsoil. In post-mining restoration, alternative
      soil substrates such as mine waste could be an adequate growth media to alleviate
      the topsoil deficit, but these materials often lack appropriate soil
      characteristics to support the development and survival of seedlings. Thus,
      addition of exogenous organic matter may be essential to enhance plant survival
      and soil function. Here, we present a case study in the arid Pilbara region
      (north-west Western Australia), a resource-rich area subject to intensive mining
      activities. The main objective of our study was to assess the effects of
      different restoration techniques such as soil reconstruction by blending
      available soil materials, sowing different compositions of plant species, and
      addition of a locally abundant native soil organic amendment (Triodia pungens
      biomass) on: (i) seedling recruitment and growth of Triodia wiseana, a dominant
      grass in Australian arid ecosystems, and (ii) soil chemical, physical, and
      biological characteristics of reconstructed soils, including microbial activity,
      total organic C, total N, and C and N mineralisation. The study was conducted in
      a 12-month multifactorial microcosms setting in a controlled environment. Our
      results showed that the amendment increased C and N contents of re-made soils,
      but these values were still lower than those obtained in the topsoil. High
      microbial activity and C mineralisation rates were found in the amended waste
      that contrasted the low N mineralisation but this did not translate into improved
      emergence or survival of T. wiseana. These results suggest a short- or medium
      term soil N immobilisation caused by negative priming effect of fresh un
      composted amendment on microbial communities. We found similar growth and
      survival rates of T. wiseana in topsoil and a blend of topsoil and waste (50:50)
      which highlights the importance of topsoil, even in a reduced amount, for plant
      establishment in arid land restoration.

PMID- 29197794
TI  - There is an association between serum high-sensitivity C-reactive protein (hs
      CRP) concentrations and depression score in adolescent girls.
AB  - BACKGROUND: Whilst there is evidence of an association between depression and
      inflammation in adults, there is limited data on this in adolescents particularly
      in non-westernized populations.  The primary aim of this study was to evaluate
      the association between serum hs-CRP level and depression score in adolescent
      girls living in northwestern Iran. METHOD: Serum hs-CRP was measured in 563
      adolescent girls aged 12-18 years. Depression score was assessed using the Beck's
      depression inventory II (BDI-II). RESULTS: Serum hs-CRP was 0.61 (0.30-0.88) mg/L
      [median (interquartile range)] in the non-depressed group, 0.97 (0.50-1.82) mg/L
      in the group with a mild depression score, 1.04 (0.57-1.60) mg/L in those with a
      moderate depression score, and 0.84 (0.45-2.64) mg/L in girls with severe
      depression (Kruskal-Wallis test, P<0.001). It has shown that hs-CRP is
      significantly higher in depressed groups. Multinomial logistic regression
      analysis, controlling for age, BMI, waist circumference, social class, alcohol
      consumption, smoking or being passive smoker and recent infections, showed that
      depression scores were positively associated with serum hs-CRP level (OR=1.93,
      P<0.001). Using a linear model after adjustment, B (the unstandardized beta) of
      hs-CRP according to the depression score was 1.43, P<0.001. CONCLUSION: There is
      a significant association between serum hs-CRP and depression score in adolescent
      girls. The cross sectional study design does not allow us to conclude that there
      is a direct relationship between inflammation and depression, and this would need
      to be tested in an intervention study.

PMID- 29197795
TI  - Reproductive steroids and ADHD symptoms across the menstrual cycle.
AB  - Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance,
      females are significantly impaired and exhibit additional comorbid disorders
      during adolescence. However, no empirical work has examined the influence of
      cyclical fluctuating steroids on ADHD symptoms in women. The present study
      examined estradiol (E2), progesterone (P4), and testosterone (T) associations
      with ADHD symptoms across the menstrual cycle in regularly-cycling young women
      (N=32), examining trait impulsivity as a moderator. Women completed a baseline
      measure of trait impulsivity, provided saliva samples each morning, and completed
      an ADHD symptom checklist every evening for 35days. Results indicated decreased
      levels of E2 in the context of increased levels of either P4 or T was associated
      with higher ADHD symptoms on the following day, particularly for those with high
      trait impulsivity. Phase analyses suggested both an early follicular and early
      luteal, or post-ovulatory, increase in ADHD symptoms. Therefore, ADHD symptoms
      may change across the menstrual cycle in response to endogenous steroid changes.

PMID- 29197796
TI  - Copper-based nanomaterials for environmental decontamination - An overview on
      technical and toxicological aspects.
AB  - Synthesis of the various types of engineered nanomaterials has gained a huge
      attention in recent years for various applications. Copper based nanomaterials
      are a branch of this category seem to be able to provide an efficient and cost
      effective way for the treatment of the persistent effluents. The present work
      aimed to study the various parameters may involve in the overall performance of
      the copper based nanomaterials for environmental clean-up purposes. To this end,
      the related characteristics of copper based nanomaterials and their effects on
      the nanomaterials reactivity and the environmental and operating parameters have
      been critically reviewed. Toxicological study of the copper based nanomaterials
      has been also considered as a factor with high importance for the selection of a
      typical nanomaterial with optimum performance and minimum environmental and
      health subsequent effects.

PMID- 29197797
TI  - Biochar application increased the growth and yield and reduced cadmium in drought
      stressed wheat grown in an aged contaminated soil.
AB  - Cadmium (Cd) and drought stress in plants is a worldwide problem, whereas little
      is known about the effect of biochar (BC) under combined Cd and drought stress.
      The current study was conducted to determine the impact of BC on Cd uptake in
      wheat sown in Cd-contaminated soil under drought stress. Wheat was grown in a
      soil after incubating the soil for 15 days with three levels of BC (0%, 3.0% and
      5.0% w/w). Three levels of drought stress (well-watered, mild drought and severe
      drought containing 70%, 50%, and 35% of soil water holding capacity respectively)
      were applied to 45-d-old wheat plants. Drought stress decreased plant height,
      spike length, chlorophyll contents, gas exchange parameters, root and shoot dry
      biomasses and grain yields. Drought stress also caused oxidative stress and
      decreased the antioxidant enzymes activities whereas increased the Cd
      concentration in plants. Biochar increased morphological and physiological
      parameters of wheat under combined drought and Cd stress and reduced the
      oxidative stress and Cd contents and increased antioxidant enzymes activities.
      The decrease in Cd concentration with BC application in drought-stressed plant
      might be attributed to BC-induced increase in crop biomass production and
      reduction in oxidative stress. These results indicate that BC could be used as an
      amendment in metal contaminated soil for improving wheat growth and reducing Cd
      concentrations under semiarid conditions.

PMID- 29197798
TI  - Individual and combined effects of fluoranthene, phenanthrene, mannitol and
      sulfuric acid on marigold (Calendula officinalis).
AB  - A study was conducted to characterize marigold stress response to polycyclic
      aromatic hydrocarbons (PAHs) (oxidative stress inducers) with and without
      sulfuric acid (S.Acid; pH 3) (acid-stress inducer), and to evaluate reactive
      oxygen species (ROS) scavenging activity of mannitol (Mann). Marigold (Calendula
      officinalis) seedlings were grown in a greenhouse and fumigated with fluoranthene
      (FLU), phenanthrene (PHE), Mann, and S.Acid individually and in various
      combinations for 40 days. Various physiological and biochemical parameters among
      others were analyzed using standard methods. The results revealed that fumigation
      of FLU induced oxidative stress to the plants via ROS generation leading to
      negative effects on photosynthesis at near saturating irradiance (Amax), stomatal
      conductance (Gs), internal carbon dioxide concentration (Ci), leaf water
      relations and chlorophyll pigments. Significant per cent inhibition of Amax
      (54%), Gs (86%) and Ci (32%), as well as per cent reductions in chlorophyll a
      (Chl.a) (33%), Chl.b (34%), and total chlorophyll (Tot. Chl) (48%) contents were
      recorded in FLU fumigated treatment in comparison to control. Combination of Mann
      with FLU scavenged the generated ROS and substantially lowered the oxidative
      stress on the plants hence all the measured parameters were not significantly
      different from control. PHE fumigation had varied effects on marigold plants and
      was not as deleterious as FLU. Combined fumigation of S.Acid with both the PAHs
      had significant negative effect on leaf water relations, and positive effect on
      fresh and turgid weight of the plants but had no effect on the other measured
      parameters. The lowest proline contents and highest catalase and ascorbate
      peroxidase activities in FLU fumigated plants further confirmed that oxidative
      stress was imposed via the generation of ROS. From the results, it is evident
      that Mann could be an efficient scavenger of ROS-generated by FLU in the marigold
      plants. We recommend Mann to be widely used for the protection of higher plants
      from FLU-generated stress in the urban areas.

PMID- 29197799
TI  - Evolution of microbial communities during electrokinetic treatment of antibiotic
      polluted soil.
AB  - The evolution of microbial communities during the electrokinetic treatment of
      antibiotic-polluted soil (EKA) was investigated with chlortetracycline (CTC),
      oxytetracycline (OTC) and tetracycline (TC) as template antibiotics. The total
      population of soil microorganisms was less affected during the electrokinetic
      process, while living anti-CTC, anti-OTC, anti-TC and anti-MIX bacteria were
      inactivated by 10.48%, 31.37%, 34.76%, and 22.08%, respectively, during the 7-day
      treatment compared with antibiotic-polluted soil without an electric field (NOE).
      Accordingly, samples with NOE treatment showed a higher Shannon index than those
      with EKA treatment, indicating a reduction of the microbial community diversity
      after electrokinetic processes. The major taxonomic phyla found in the samples of
      EKA and NOE treatment were Proteobacteria, Bacteroidetes, Firmicutes and
      Actinobacteria. And the distribution of Actinobacteria, Cyanobacteria, and
      Chloroflexi was greatly decreased compared with blank soil. In the phylum
      Proteobacteria, the abundance of Alphaproteobacteria was greatly reduced in the
      soils supplemented with antibiotics (from 13.40% in blank soil to 6.43-10.16%
      after treatment); while Betaproteobacteria and Deltaproteobacteria showed a
      different trend with their abundance increased compared to blank soil, and
      Gammaproteobacteria remained unchanged for all treatments (2.36-2.78%). The
      varied trends for different classes indicated that the major bacterial groups
      changed with the treatments due to their different adaptability to the
      antibiotics as well as to the electric field. SulI being an exception, the
      reduction ratio of the observed antibiotic resistance genes (ARGs) including
      tetC, tetG, tetW, tetM, intI1, and sulII in the 0-2cm soil sampled with EKA
      versus NOE treatment reached 55.17%, 3.59%, 99.26%, 89.51%, 30.40%, and 27.92%,
      respectively. Finally, correlation analysis was conducted between antibiotic
      resistant bacteria, ARGs and taxonomic bacterial classes. It was found that sulII
      was the most representative of many different bacteria among the seven ARGs
      studied. This is the first report on the changes in microbial communities before
      and after EKA, and the present results demonstrated that the application of EKA
      is a useful and effective approach to suppressing both antibiotic resistant
      microorganisms and ARGs.

PMID- 29197800
TI  - Progesterone suppresses Abeta42-induced neuroinflammation by enhancing autophagy
      in astrocytes.
AB  - Autophagy is an intracellular catabolic mechanism essential for recycling
      intracellular unfolding protein and eliminating toxic protein aggregates. Several
      studies have shown that deficient autophagy is implicated in the development of
      Alzheimer's disease (AD) progression. To date, rapidly emerging evidence suggests
      that neurosteroid progesterone (PG) may play an important role in ameliorating
      AD. However, the role of PG and its neuroprotective mechanism in regulating
      autophagy still require further investigation. Here, we investigated the
      protective effects of PG against Abeta-induced inflammatory responses in
      astrocytes and its underlying mechanism in mediating autophagy. Remarkably, Abeta
      induced astrocyte dysfunction in autophagic activation and up-regulated
      inflammatory secretion. However, the autophagy inducer rapamycin (RAPA)
      significantly suppressed Abeta-induced inflammation in astrocytes. In astrocytes,
      treatment with Abeta caused autophagy deficiency, whereas PG significantly
      increased autophagy activation. Finally, PG suppressed Abeta-induced
      neuroinflammatory production via enhancing autophagy together with regulating
      mTOR signaling. Taken together, these results show that autophagy is a vital
      mechanism against Abeta-induced neuroinflammatory responses in astrocytes and
      demonstrate the potential neuroprotective mechanism of PG in suppressing
      neuroinflammatory responses by enhancing autophagy. Therefore, uncovering the
      neuroprotective mechanism of PG may provide new insight into novel therapies for
      the amelioration of AD.

PMID- 29197801
TI  - In contrast to morphine, buprenorphine enhances macrophage-induced humoral
      immunity and, as oxycodone, slightly suppresses the effector phase of cell
      mediated immune response in mice.
AB  - BACKGROUND: Opioid receptors are commonly expressed on various immune cells,
      macrophages especially. Thus, these cells are prone to stimulation with opioids,
      which seems to be responsible for opioid-induced immunomodulatory effects. While
      morphine, fentanyl and methadone influence on mouse immune response was recently
      studied, little is known about the potential immunomodulatory impact of
      buprenorphine and oxycodone. AIM: The current research aimed to investigate the
      influence of buprenorphine and oxycodone on immune responses in mice under
      homeostatic conditions. METHODS AND RESULTS: Repeated administration of morphine
      led to intensification of CHS response in actively sensitized mice, while
      buprenorphine or oxycodone administration exerted the opposite effect. Further,
      hapten-conjugated macrophages from mice treated with morphine, when transferred
      into naive recipients, induced more potent CHS response. The enhanced generation
      of reactive oxygen intermediates and nitric oxide by macrophages from mice
      treated with buprenorphine, oxycodone or morphine was also shown, along with
      increased release of IL-6, TNFalpha and TGFbeta. Treatment with opioids altered
      expression of antigen phagocytosis and presentation markers. Finally, the
      inhibitory effect of morphine treatment on induction of humoral immunity by
      macrophages was demonstrated, while oxycodone failed to influence humoral immune
      response and buprenorphine actually enhanced B-cell activation. CONCLUSIONS:
      Current observations confirm that macrophages greatly contribute to
      immunomodulatory effects of opioids. Studies on immunomodulation by opioids have
      great importance related to the evaluation of its beneficial and adverse effects
      on patient condition. Our research showed that oxycodone exerts the weakest
      immunomodulatory properties, allowing us to assume this drug as safer than
      morphine during prolonged therapy.

PMID- 29197802
TI  - Developing the next generation of graphene-based platforms for cancer
      therapeutics: The potential role of reactive oxygen species.
AB  - Graphene has a promising future in applications such as disease diagnosis, cancer
      therapy, drug/gene delivery, bio-imaging and antibacterial approaches owing to
      graphene's unique physical, chemical and mechanical properties alongside minimal
      toxicity to normal cells, and photo-stability. However, these unique features and
      bioavailability of graphene are fraught with uncertainties and concerns for
      environmental and occupational exposure. Changes in the physicochemical
      properties of graphene affect biological responses including reactive oxygen
      species (ROS) production. Lower production of ROS by currently available
      theranostic agents, e.g. magnetic nanoparticles, carbon nanotubes, gold
      nanostructures or polymeric nanoparticles, restricts their clinical application
      in cancer therapy. Oxidative stress induced by graphene accumulated in living
      organs is due to acellular factors which may affect physiological interactions
      between graphene and target tissues and cells. Acellular factors include particle
      size, shape, surface charge, surface containing functional groups, and light
      activation. Cellular responses such as mitochondrial respiration, graphene-cell
      interactions and pH of the medium are also determinants of ROS production. The
      mechanisms of ROS production by graphene and the role of ROS for cancer
      treatment, are poorly understood. The aim of this review is to set the
      theoretical basis for further research in developing graphene-based theranostic
      platforms.

PMID- 29197804
TI  - Cytotoxicity mechanisms in melanoma cells and UPLC-QTOF/MS2 chemical
      characterization of two Brazilian stingless bee propolis: Uncommon presence of
      piperidinic alkaloids.
AB  - The present study characterized propolis extracts produced by Scaptotrigona
      bipunctata (Tubuna) and Melipona quadrifasciata (Mandacaia) by LC-MS/MS; their
      cytotoxicity as well as the mechanism of action in a melanoma cellular model were
      also assessed. The chemical characterization performed by UPLC-ESI-QTOF/MS2
      analysis revealed uncommon presence of piperidinic alkaloids in Tubuna's propolis
      extract together with C-glycopyranoside flavonoids. Mandacaia's propolis
      collected in the same area rather presented terpenoids and flavonoids. Regarding
      the mechanism of cytotoxicity, propolis extracts increased the accumulation of
      reactive oxygen species (ROS), reduced the potential of mitochondrial membrane,
      induced a decrease in the proteins Bcl-2 and AKT-3 levels, and decreased melanoma
      cells' migration and invasion. Both propolis extracts induced apoptosis while
      only Mandacaia's propolis extract induced cell cycle arrest in G2/M.

PMID- 29197803
TI  - Redox system and phospholipid metabolism in the kidney of hypertensive rats after
      FAAH inhibitor URB597 administration.
AB  - Primary and secondary hypertension is associated with kidney redox imbalance
      resulting in enhanced reactive oxygen species (ROS) and enzymes dependent
      phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597,
      modulates the levels of endocannabinoids, particularly of anandamide, which is
      responsible for controlling blood pressure and regulating redox balance.
      Therefore, this study aimed to compare the effects of chronic URB597
      administration to spontaneously hypertensive rats (SHR) and rats with secondary
      hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox
      and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH)
      inhibitor decreased the activity of ROS-generated enzymes what resulted in a
      reduction of ROS level. Moreover varied changes in antioxidant parameters were
      observed with tendency to improve antioxidant defense in SHR kidney. Moreover,
      URB597 administration to hypertensive rats decreased pro-inflammatory response,
      particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency
      to enhance ROS-dependent phospholipid oxidation, estimated by changes in
      neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and
      malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH
      inhibitor resulted in increased level of endocannabinoids in kidney of both
      groups of hypertensive rats led to enhanced expression of the cannabinoid
      receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA
      salt rats. URB597 given to normotensive rats also affected kidney oxidative
      metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats
      and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids
      and cannabinoid receptors were significantly higher in both control groups of
      rats after URB597 administration. In conclusion, because URB597 disturbed the
      kidney redox system and phospholipid ROS-dependent and enzymatic-dependent
      metabolism, the administration of this inhibitor may enhance kidney disorders
      depending on model of hypertension, but may also cause kidney disturbances in
      control rats. Therefore, further studies are warranted.

PMID- 29197805
TI  - New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.
AB  - Recently, illegal sildenafil analogues have emerged, causing serious social
      issues. In spite of the importance of sildenafil analogues, their metabolic
      profiles or clinical effects have not been reported yet. In this study, new
      metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil,
      and hydroxyhomosildenafil were determined using liquid chromatography quadrupole
      time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q
      TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were
      performed. For in vivo metabolites analysis, urine and feces samples of rats
      treated with sildenafil analogues were analyzed. For in vitro metabolites
      analysis, human liver microsomes incubated with sildenafil analogues were
      extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC
      Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in
      hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples,
      respectively. These results could be applied to forensic science and other
      analytical fields. Moreover, these newly identified metabolites could be used as
      fundamental data to determine the side effect and toxicity of illegal sildenafil
      analogues.

PMID- 29197806
TI  - Immunofluorescence-based biosensor for the determination of dengue virus NS1 in
      clinical samples.
AB  - The sharp increase in incidence of dengue infection has necessitated the
      development of methods for the rapid diagnosis of this deadly disease. Here we
      report the design and development of a reliable, sensitive, and specific optical
      immunosensor for the detection of the dengue nonstructural protein 1 (NS1)
      biomarker in clinical samples obtained during early stages of infection. The
      present optical NS1 immunosensor comprises a biosensing surface consisting of
      specific monoclonal NS1 antibody for immunofluorescence-based NS1 antigen
      determination using fluorescein isothiocyanate (FITC) conjugated to IgG antibody.
      The linear range of the optical immunosensor was from 15-500ngmL-1, with
      coefficient of determination (R2) of 0.92, high reproducibility (the relative
      standard deviation obtained was 2%), good stability for 21days at 4 degrees C,
      and low detection limit (LOD) at 15ngmL-1. Furthermore, the optical immunosensor
      was capable of detecting NS1 analytes in plasma specimens from patients infected
      with the dengue virus, with low cross-reaction with plasma specimens containing
      the Japanese encephalitis virus (JEV) and Zika virus. No studies have been
      performed on the reproducibility and cross-reactivity regarding NS1 specificity,
      which is thus a limitation for optical NS1 immunosensors. In contrast, the
      present study addressed these limitations carefully where these two important
      experiments were conducted to showcase the robustness of our newly developed
      optical-based fluorescence immunosensor, which can be practically used for direct
      NS1 determination in any untreated clinical sample.

PMID- 29197807
TI  - Effect of carboxylic acids on the properties of zerovalent iron toward adsorption
      and degradation of trichloroethylene.
AB  - Zerovalent iron (ZVI) based technology has been applied to remediate contaminated
      groundwater and has been paid great attention as an economic alternative. But it
      is still remains highly challenging to remove chlorinated pollutants such as
      trichloroethylene (TCE) with ZVI. Low molecular weight carboxylic ligands (formic
      acid (FA), oxalic acid (OA), and citric acid (CA)) were chosen to study the
      influence on the performance of ZVI in groundwater, including the morphology of
      Fe surface and the Fe dissolution. The removal rate of TCE with ZVI in the
      presence of 30 mM carboxylic groups followed an order of FA > OA > pure water ?
      CA. FA provides protons to promote the surface corrosion and generated more
      magnetite on the ZVI surface, which was further responsible for a high adsorption
      of TCE. With the strong complexing ability of OA and CA, passive layers could
      form dissoluble complexes via a ligand-promoted dissolution process. However,
      high concentration of OA resulted in Fe oxalate reprecipitated back onto the ZVI
      surface then inhibited the reactivity of ZVI. The Fe-ligand complexes also have
      ability to transform TCE depending on their redox properties. It is expected that
      effectiveness of carboxylic ligands on the ZVI: those low molecular weight
      carboxylic ligands in groundwater and soil may enhance the reaction efficiency of
      ZVI by altering the surface characteristics of ZVI. Therefore, the carboxylic
      ligands could increase the reactivity and the longevity of ZVI.

PMID- 29197808
TI  - Thermal remediation alters soil properties - a review.
AB  - Contaminated soils pose a risk to human and ecological health, and thermal
      remediation is an efficient and reliable way to reduce soil contaminant
      concentration in a range of situations. A primary benefit of thermal treatment is
      the speed at which remediation can occur, allowing the return of treated soils to
      a desired land use as quickly as possible. However, this treatment also alters
      many soil properties that affect the capacity of the soil to function. While
      extensive research addresses contaminant reduction, the range and magnitude of
      effects to soil properties have not been explored. Understanding the effects of
      thermal remediation on soil properties is vital to successful reclamation, as
      drastic effects may preclude certain post-treatment land uses. This review
      highlights thermal remediation studies that have quantified alterations to soil
      properties, and it supplements that information with laboratory heating studies
      to further elucidate the effects of thermal treatment of soil. Notably, both
      heating temperature and heating time affect i) soil organic matter; ii) soil
      texture and mineralogy; iii) soil pH; iv) plant available nutrients and heavy
      metals; v) soil biological communities; and iv) the ability of the soil to
      sustain vegetation. Broadly, increasing either temperature or time results in
      greater contaminant reduction efficiency, but it also causes more severe impacts
      to soil characteristics. Thus, project managers must balance the need for
      contaminant reduction with the deterioration of soil function for each specific
      remediation project.

PMID- 29197809
TI  - A model for measuring the environmental sustainability of events.
AB  - Like all human activities, events can generate significant pressures on
      environmental resources, unless they are well-managed and monitored. Therefore,
      it is becoming more and more important to develop models that can measure their
      environmental sustainability. Although increasing attention is being paid to this
      sector, there is currently no standard protocol or method to assess the eco
      sustainability of events. This article presents an innovative assessment
      procedure to measure the environmental sustainability of events. It is based on
      several indicators, combined by means of a multi-criteria approach and aggregated
      into a final index, which we called METER (Measuring Events Through Environmental
      Research). The METER index uses nine major operational categories, divided in sub
      categories and detailed items, which cover all the main aspects concerning
      environmental sustainability of an event and are evaluated for all its phases,
      i.e. planning, organisation, implementation, post event. The index is fairly
      analytical, and is thus able to represent the numerous aspects to be taken into
      consideration in the environmental assessment of an event. At the same time, it
      is simple to apply and user-friendly, thanks to its graphics and effective
      communication of the web platform within it is implemented. Moreover, METER is
      based on a participatory approach using the bottom-up model and on the principle
      of subsidiarity. All official international documents regarding sustainable
      development now require subsidiarity. However, it is not being currently applied
      as part of any certification or with any evaluation tool. Therefore, although the
      index is still a prototype, it represents an innovation in the field of
      environmental management. A simple exemplary case is presented, about a European
      Spring School held at University of Perugia (Italy) in 2014, in which the
      application of METER showed a sustainability assessment score of 638 points out
      of 1000, with an excellent management of waste, catering, internal travel and
      participation aspects.

PMID- 29197810
TI  - An assessment on the environmental contamination caused by the Fukushima
      accident.
AB  - The radiological releases from the damaged fuel to the atmosphere and into the
      cooling water in the Fukushima Daiich Nuclear Power Plant (FDNPP) accident are
      investigated. Atmospheric releases to the land and ocean mostly occurred during
      the first week after the accident whereas continuous release from the damaged
      fuel into the cooling water resulted in an accumulation of contaminated water in
      the plant during last six years. An evaluation of measurement data and analytical
      model for the release of radionuclides indicated that atmospheric releases were
      mainly governed by the volatility of the radionuclides. Using the measurement
      data on the contaminated water, the mechanism for the release of long-lived
      radionuclides into the cooling water was analyzed. It was found that the
      radioactivity concentrations of 90Sr in the contaminated water in the Primary
      Containment Vessel (PCV) of unit 2 and unit 3 were consistently higher than that
      of 137Cs and the radioactivity concentration of 90Sr in the turbine building of
      unit 1 in year 2015 was higher than that in year 2011. It was also observed that
      the radioactivity concentration of long-lived radionuclides in the contaminated
      water in the FDNPP is still high even in year 2015. The activity ratio of
      238Pu/239+240Pu for the contaminated water was in the range of 1.7-5.4, which was
      significantly different from the ratios from the soil samples representing the
      atmospheric releases of FDNPP. It is concluded that the release mechanisms into
      the atmosphere and cooling water are clearly different and there has been
      significant amount of long-lived radionuclides released into the contaminated
      water.

PMID- 29197811
TI  - Physical examination of dizziness in athletes after a concussion: A descriptive
      study.
AB  - BACKGROUND: Dizziness is commonly reported after concussion. With the forces
      experienced at the time of the injury, several anatomical locations may have been
      altered, causing dizziness. OBJECTIVE: Describe an objective examination and the
      types of impairment/dysfunction implicated by the results of clinical examination
      tests in subjects with dizziness after a concussion. DESIGN: Cross-Sectional.
      METHODS: Athletes between ages 10-23 were enrolled with a diagnosis of
      concussion. An examination was completed to identify areas potentially
      contributing to dizziness, including tests of oculomotor control, the vestibular
      system, neuromotor control, and musculoskeletal components of the cervical spine.
      Descriptive analyses were completed to define the anatomical areas/types of
      dysfunction identified by positive findings of the examination tests. RESULTS:
      All (n = 41; 100%) subjects had examination findings consistent with central
      dysfunction. Of these, 36 (97.8%) had oculomotor control deficits; 29 (70.7%)
      demonstrated motion sensitivity; and 6 (15%) had central vestibular deficits.
      Nineteen (46.3%) had peripheral dysfunction, including 18 (43.9%) with unilateral
      hypofunction, and 2 (4.9%) with Benign Paroxysmal Positional Vertigo. Thirty-four
      (82.9%) had cervical dysfunction, with 11 (26.8%) presenting with cervicogenic
      dizziness, and 31 (75.6%) with altered neuromotor control. CONCLUSIONS:
      Functional injury to centrally-mediated pathways, specifically oculomotor
      control, and afferent and efferent pathways in the cervical spine are commonly
      identified through clinical examination tests in individuals with a complaint of
      dizziness post-concussion. According to results presented here, a high majority
      (90%) of the participants demonstrated dizziness that appeared to be
      multifactorial in nature and was not attributable to one main type of
      dysfunction. The common pathways between the systems make it difficult to isolate
      only one anatomical area as a contributor to dizziness.

PMID- 29197812
TI  - An optical fiber-based LSPR aptasensor for simple and rapid in-situ detection of
      ochratoxin A.
AB  - Label-free biosensing methods that rely on the use of localized surface plasmon
      resonance (LSPR) have attracted great attention as a result of their simplicity,
      high sensitivity, and relatively low cost. However, in-situ analysis of real
      samples using these techniques has remained challenging because colloidal
      nanoparticles (NPs) can be unstable at certain levels of pH and salt
      concentration. Even in the case of a chip-type LSPR sensor that can resolve the
      instability problem by employing NPs immobilized on the substrate, loading of a
      sample to sensor chip with exact volume control can be difficult for unskilled
      users. Herein, we report an optical-fiber-based LSPR aptasensor that can avoid
      these problems and serve as a portable and simple system for sensitive detection
      of a small mycotoxin, ochratoxin A (OTA), in real samples. The optical fiber
      coated with aptamer-modified gold nanorods (GNRs) is simply dipped into a
      solution containing OTA and subjected to LSPR analysis. Quantitative analysis of
      OTA is performed by measuring the spectral red shift of the LSPR peak of GNRs.
      Under optimized conditions, the LSPR peak shift displays a linear response (R2 =
      0.9887) to OTA in the concentration range from 10pM to 100nM, with a limit of
      detection of 12.0pM (3S). The developed sensor shows a high selectivity for OTA
      over other mycotoxins such as zearalenone (ZEN) and ochratoxin B (OTB), and shows
      an accurate detection capability for OTA in real grape juice samples.

PMID- 29197813
TI  - Distribution and ecological risk assessment of cadmium in water and sediment in
      Longjiang River, China: Implication on water quality management after pollution
      accident.
AB  - In early January 2012, the Longjiang River was subjected to a serious cadmium
      (Cd) pollution accident, which led to negatively environmental and social
      impacts. A series of measures of emergency treatment were subsequently taken to
      reduce water Cd level. However, little information was available about the change
      of Cd level in environmental matrices and long-term effect of this pollution
      accident to aquatic ecosystem. Thus, this study investigated the distribution of
      Cd in water and sediment of this river for two years since pollution accident, as
      well as assessed its ecological risk to aquatic ecosystem of Longjiang River. The
      results showed that it was efficient for taking emergency treatment measures to
      decrease water Cd concentration to below the threshold value of national drinking
      water quality standard of China. There was high risk (HQ > 1) to aquatic
      ecosystem in some of reaches between February and July 2012, but low or no risk
      (HQ < 1) between December 2012 to December 2013. Cd concentration in sediment in
      polluted reaches increased after pollution accident and emergency treatments in
      2012, but decreased in 2013. During flood period, the sediment containing high
      concentration of Cd in Longjiang River was migrated to downstream Liujiang River.
      Cd content in sediment was reduced to background level after two years of the
      pollution accident occurrence. The study provides basic information about Cd
      levels in different media after pollution accident, which is helpful in
      evaluating the effectiveness of emergency treatments and the variation of
      ecological risk, as well as in conducting water management and conservation.

PMID- 29197814
TI  - Microscopic insight into precipitation and adsorption of As(V) species by Fe
      based materials in aqueous phase.
AB  - The mechanism of As(V) removal from the drinking water and industrial effluents
      by iron materials remains unclear at the molecular level. In this work, the
      association of Fe-based materials with As(V) species was explored using density
      functional theory and ab initio calculations. Solvent separated ion pair
      structures of [FeH2AsO4]2+aq species may be dominant in an acidic solution of
      FeAs complex. The association trend of H2AsO4- species by Fe3+aq is found to be
      quite weak in the aqueous solution, which may be attributed to the strong
      hydration of Fe3+aq and [FeH2AsO4]2+ species. However, the association of H2AsO4-
      species by colloidal clusters is quite strong, due to the weakened hydration of
      Fe(III) in colloidal structures. The hydrophobicity of Fe-based materials may be
      one of the key factors for their As(V) removal efficiency in an aqueous phase.
      When the number of OH- coordinated with Fe(III) increases, the association trend
      of As(V) by colloidal ferric hydroxides weakens accordingly. This study provides
      insights into understanding the coprecipitation and adsorption mechanisms of
      arsenate removal and revealing the high efficiency of arsenate removal by
      colloidal ferric hydroxides or iron salts under moderate pH conditions.

PMID- 29197815
TI  - Nano-litter from cigarette butts: Environmental implications and urgent
      consideration.
AB  - Cigarette butts (CGB) are equivalent to plastic litter in terms of number of
      pieces released directly into the environment. Due to their small size and social
      use, CGB are commonly found in natural systems, and several questions have been
      raised concerning the contaminants that are released with CGB, including metals,
      organic species, and nanoparticles. The aim of the present study is to
      investigate the release of nanoscale particles from CGB by leaching with
      rainwater. After seven days of passive stirring of both smoked and unsmoked CGB
      in synthetic rainwater, the solutions were treated and analyzed by specific nano
      analytical methods. Our results demonstrate the release of 4.12 +/- 0.24% (w/CGB)
      organic carbon in the range of 10 nm up to 400 nm and with a z-average diameter
      of 202.4 +/- 74.1 nm. The fractal dimension (Df) of the nanoscale particles
      ranges from 1.14 to 1.52 and suggests a soot (carbon)-based composition. The
      analysis of some metallic species (As, Pb, Cd, Cu, Ni, Cr, Co, Al, Mn, Zn, and
      Fe) shows that these species are essentially attached to the nanoscale particles
      per gram of carbon released. By considering the diffusion of the nanomaterials
      into different environmental compartments, our results suggest a new emerging and
      global contamination of the environment by cigarette butts, comparable to plastic
      litter, which urgently needs to be considered.

PMID- 29197816
TI  - Influence of biomass acclimation on the performance of a partial nitritation
      anammox reactor treating industrial saline effluents.
AB  - The performance of the partial nitritation/anammox processes was evaluated for
      the treatment of fish canning effluents. A sequencing batch reactor (SBR) was fed
      with industrial wastewater, with variable salt and total ammonium nitrogen (TAN)
      concentrations in the range of 1.75-18.00 g-NaCl L-1 and 112 - 267 mg-TAN L-1.
      The SBR operation was divided into two experiments: (A) progressive increase of
      salt concentrations from 1.75 to 18.33 g-NaCl L-1; (B) direct application of high
      salt concentration (18 g-NaCl L-1). The progressive increase of NaCl
      concentration provoked the inhibition of the anammox biomass by up to 94% when 18
      g-NaCl L-1 were added. The stable operation of the processes was achieved after
      154 days when the nitrogen removal rate was 0.021 +/- 0.007 g N/L.d
      (corresponding to 30% of removal efficiency). To avoid the development of NOB
      activity at low salt concentrations and to stabilize the performance of the
      processes dissolved oxygen was supplied by intermittent aeration. A greater
      removal rate of 0.029 +/- 0.017 g-N L-1 d-1 was obtained with direct exposure of
      the inoculum to 18 g-NaCl L-1 in less than 40 days. Also, higher specific
      activities than those from the inoculum were achieved for salt concentrations of
      15 and 20 g-NaCl L-1 after 39 days of operation. This first study of the
      performance of the partial nitritation/anammox processes, to treat saline
      wastewaters, indicates that the acclimation period can be avoided to shorten the
      start-up period for industrial application purposes. Nevertheless, further
      experiments are needed in order to improve the efficiency of the processes.

PMID- 29197817
TI  - Binary culture of microalgae as an integrated approach for enhanced biomass and
      metabolites productivity, wastewater treatment, and bioflocculation.
AB  - Ecological studies of microalgae have revealed their potential to co-exist in the
      natural environment. It provides an evidence of the symbiotic relationship of
      microalgae with other microorganisms. The symbiosis potential of microalgae is
      inherited with distinct advantages, providing a venue for their scale-up
      applications. The deployment of large-scale microalgae applications is limited
      due to the technical challenges such as slow growth rate, low metabolites yield,
      and high risk of biomass contamination by unwanted bacteria. However, these
      challenges can be overcome by exploring symbiotic potential of microalgae. In a
      symbiotic system, photosynthetic microalgae co-exist with bacteria, fungi, as
      well as heterotrophic microalgae. In this consortium, they can exchange nutrients
      and metabolites, transfer gene, and interact with each other through complex
      metabolic mechanism. Microalgae in this system, termed as a binary culture, are
      reported to exhibit high growth rate, enhanced bio-flocculation, and biochemical
      productivity without experiencing contamination. Binary culture also offers
      interesting applications in other biotechnological processes including
      bioremediation, wastewater treatment, and production of high-value metabolites.
      The focus of the study is to provide a perspective to enhance the understanding
      about microalgae binary culture. In this review, the mechanism of binary culture,
      its potential, and limitations are briefly discussed. A number of queries are
      evolved through this study, which needs to be answered by executing future
      research to assess the real potential of binary culture.

PMID- 29197818
TI  - Application of volume-retarded osmosis and low-pressure membrane hybrid process
      for water reclamation.
AB  - A new concept of volume-retarded osmosis and low-pressure membrane (VRO-LPM)
      hybrid process was developed and evaluated for the first time in this study.
      Commercially available forward osmosis (FO) and ultrafiltration (UF) membranes
      were employed in a VRO-LPM hybrid process to overcome energy limitations of draw
      solution (DS) regeneration and production of permeate in the FO process. To
      evaluate its feasibility as a water reclamation process, and to optimize the
      operational conditions, cross-flow FO and dead-end mode UF processes were
      individually evaluated. For the FO process, a DS concentration of 0.15 g mL-1 of
      polysulfonate styrene (PSS) was determined to be optimal, having a high flux with
      a low reverse salt flux. The UF membrane with a molecular weight cut-off of 1 kDa
      was chosen for its high PSS rejection in the LPM process. As a single process, UF
      (LPM) exhibited a higher flux than FO, but this could be controlled by adjusting
      the effective membrane area of the FO and UF membranes in the VRO-LPM system. The
      VRO-LPM hybrid process only required a circulation pump for the FO process. This
      led to a decrease in the specific energy consumption of the VRO-LPM process for
      potable water production, that was similar to the single FO process. Therefore,
      the newly developed VRO-LPM hybrid process, with an appropriate DS selection, can
      be used as an energy efficient water production method, and can outperform
      conventional water reclamation processes.

PMID- 29197819
TI  - Effects of the neonicotinoids acetamiprid and thiacloprid in their commercial
      formulations on soil fauna.
AB  - Neonicotinoids are the most prominent group of insecticides in the world and are
      commercialized in over 120 countries for the control of agricultural pests mainly
      due to their broad-spectrum activity and versatility in application. Though non
      target soil organisms are likely to be exposed during application, there is
      paucity of information in scientific literature regarding their sensitivity to
      neonicotinoids. This study attempts to fill this gap by evaluating, under
      laboratory conditions, the chronic toxicity of the neonicotinoids thiacloprid and
      acetamiprid, through their commercial formulations (CF), to the soil
      invertebrates Folsomia candida, Eisenia andrei and Enchytraeus crypticus. Results
      obtained indicate that the relative reproductive sensitivity of the test
      organisms can be expressed as: F. candida = E. andrei > E. crypticus (for
      acetamiprid CF) and E. andrei > F. candida > E. crypticus (for thiacloprid CF).
      To extrapolate from laboratory test results to field conditions, predicted
      environmental concentrations (PECs) and predicted no-effect concentrations were
      derived. Calculated toxicity-exposure ratios (TER = EC10/PEC) were below trigger
      values for acetamiprid and thiacloprid, when estimated with initial PEC. While
      estimated hazard quotients (HQ = PEC/PNEC), were greater than the European
      Commission trigger value. Therefore, with the current data under standard
      environmental risk assessment schemes it can be considered that the risk of
      thiacloprid and acetamiprid to the soil compartment is unacceptable. However,
      further research into the effects of these substances on different organisms is
      required to increase the confidence in the risk assessment estimates for
      instance, by calculating hazardous concentrations using species sensitivity
      distribution curves.

PMID- 29197821
TI  - Penicillium purpurogenum produces a novel endo-1,5-arabinanase, active on
      debranched arabinan, short arabinooligosaccharides and on the artificial
      substrate p-nitrophenyl arabinofuranoside.
AB  - Penicillium purpurogenum secretes numerous lignocellulose-degrading enzymes,
      including four arabinofuranosidases and an exo-arabinanase. In this work, the
      biochemical properties of an endo-arabinanase (ABN1) are presented. A gene,
      coding for a potential ABN was mined from the genome. It includes three introns.
      The cDNA is 975 bp long and codes for a mature protein of 324 residues. The cDNA
      was expressed in Pichia pastoris. The enzyme is active on debranched arabinan and
      arabinooligosaccharides. In contrast to other characterized ABNs, inactive on p
      nitrophenyl-alpha-L-arabinofuranoside (pNPAra), ABN1 is active on this substrate.
      The enzyme has an optimal pH of 4.5 and an optimal temperature of 30-35  degrees
      C. Calcium does not activate ABN1. ABN1 belongs to GH family 43 sub-family 6, and
      a Clustal alignment with sequences of characterized fungal ABNs shows highest
      identity (54.6%) with an ABN from Aspergillus aculeatus. A three-dimensional
      model of ABN1 was constructed and the docking with pNPAra was compared with
      similar models of an enzyme very active on this substrate and another lacking
      activity, both from GH family 43. Differences in the number of hydrogen bonds
      between enzyme and substrate, and distance between the substrate and the
      catalytic residues may explain the differences in activity shown by these
      enzymes.

PMID- 29197820
TI  - Demonstration of a consensus approach for the calculation of physicochemical
      properties required for environmental fate assessments.
AB  - Eight software applications are compared for their performance in estimating the
      octanol-water partition coefficient (Kow), melting point, vapor pressure and
      water solubility for a dataset of polychlorinated biphenyls, polybrominated
      diphenyl ethers, polychlorinated dibenzodioxins, and polycyclic aromatic
      hydrocarbons. The predicted property values are compared against a curated
      dataset of measured property values compiled from the scientific literature with
      careful consideration given to the analytical methods used for property
      measurements of these hydrophobic chemicals. The variability in the predicted
      values from different calculators generally increases for higher values of Kow
      and melting point and for lower values of water solubility and vapor pressure.
      For each property, no individual calculator outperforms the others for all four
      of the chemical classes included in the analysis. Because calculator performance
      varies based on chemical class and property value, the geometric mean and the
      median of the calculated values from multiple calculators that use different
      estimation algorithms are recommended as more reliable estimates of the property
      value than the value from any single calculator.

PMID- 29197822
TI  - Radiation resistant PIDECalpha cell using photon intermediate direct energy
      conversion and a 210Po source.
AB  - Radiation damage is a significant concern with both alphavoltaic and betavoltaic
      cells because their performance degrades, especially with high-energy - (>200keV)
      beta and alpha particles. Indirect excitation methods, such as the Photon
      Intermediate Direct Energy Conversion (PIDEC) framework, can protect the
      transducer from radiation. A nuclear battery using a 90Sr beta source was
      constructed by the author's research group, which demonstrated the radiation
      resistance of a PIDEC cell driven by beta particles (PIDECbeta cell). Use of
      alpha sources to drive nuclear batteries would appear to be much more attractive
      than beta sources due to higher potential power density. However, they are also
      subject to higher rates of radiation damage. This paper describes the successful
      incorporation of alpha particles into the PIDEC framework using the alpha emitter
      210Po to form a PIDECalpha cell. The PIDECalpha cell transducer was exposed to
      alpha particles for over one year without experiencing adverse effects from
      radiation damage.

PMID- 29197823
TI  - Bacterial social interactions and the emergence of community-intrinsic
      properties.
AB  - Bacterial communities are dominated and shaped by social interactions, which
      facilitate the emergence of properties observed only in the community setting.
      Such community-intrinsic properties impact not only the phenotypes of cells in a
      community, but also community composition and function, and are thus likely to
      affect a potential host. Studying community-intrinsic properties is, therefore,
      important for furthering our understanding of clinical, applied and environmental
      microbiology. Here, we provide recent examples of research investigating
      community-intrinsic properties, focusing mainly on community composition and
      interactions in multispecies biofilms. We hereby wish to emphasize the importance
      of studying social interactions in settings where community-intrinsic properties
      are likely to emerge.

PMID- 29197824
TI  - Measurement of harms in community care: a qualitative study of use of the NHS
      Safety Thermometer.
AB  - OBJECTIVES: Measurement is a vital part of improvement work. While it is known
      that the context of improvement work influences its success, less is known about
      how context affects measurement of underlying harms. We sought to explore the use
      of a harm measurement tool, the NHS Safety Thermometer (NHS-ST), designed for use
      across diverse healthcare settings in the particular context of community care.
      METHODS: This is a qualitative study of 19 National Health Service (NHS)
      organisations, 7 of which had community service provision. We conducted
      ethnographic observations of practice and interviews with front-line nursing and
      senior staff. Analysis was based on the constant comparison method. RESULTS:
      Measurement in community settings presents distinct challenges, calling into
      question the extent to which measures can be easily transferred. The NHS-ST was
      seen as more appropriate for acute care, not least because community nurses did
      not have the same access to information. Data collection requirements were in
      tension with maintaining a relationship of trust with patients. The aim to
      collect data across care settings acted to undermine perceptions of the
      representativeness of community data. Although the tool was designed to measure
      preventable harms, care providers questioned their preventability within a
      community setting. Different harms were seen as priorities for measurement and
      improvement within community settings. CONCLUSIONS: Measurement tools are
      experienced by healthcare staff as socially situated. In the community setting,
      there are distinct challenges to improving care quality not experienced in the
      acute sector. Strategies to measure harms, and use of any resulting data for
      improvement work, need to be cognisant of the complexity of an environment where
      healthcare staff often have little opportunity to monitor and influence patients.

PMID- 29197825
TI  - Choriocapillaris flow deficit in Bietti crystalline dystrophy detected using
      optical coherence tomography angiography.
AB  - BACKGROUND/AIMS: This study aimed to evaluate blood flow in the choriocapillaris
      in patients with Bietti crystalline dystrophy (BCD) with CYP4V2 mutations using
      optical coherence tomography angiography (OCTA), and to explore the parameters
      associated with visual function. METHODS: This prospective case-series study
      included 13 eyes of 13 consecutive patients with BCD with CYP4V2 mutations and 20
      healthy eyes. Using OCTA, we obtained en face images of blood flow in the
      choriocapillaris. The residual choriocapillaris area on en face images in a 10
      degrees *10 degrees  macular cube was manually measured and graded according to
      whether the choriocapillaris remained at the subfovea. We also investigated
      factors associated with visual acuity (VA) and the mean deviation (MD) value
      using a Humphrey field analyser with a 10-2 Swedish Interactive Threshold
      Algorithm standard program among OCTA-derived parameters. RESULTS:
      Choriocapillaris blood flow deficit was observed in 12 eyes (92%), whereas this
      was observed in none of healthy eyes. The adjusted residual choriocapillaris area
      was 2.47+/-1.79 mm2. The presence of the choriocapillaris at the subfovea was
      significantly correlated with VA and the MD value (P=0.006, r=0.71; P=0.04, r=
      0.59, respectively). CONCLUSIONS: Using OCTA, choriocapillaris blood flow deficit
      could be observed in most patients with BCD with CYP4V2 mutations. The presence
      of the choriocapillaris at the subfovea was significantly correlated with visual
      function in these patients. Analysis of choriocapillaris blood flow using OCTA
      allows non-invasive assessment of the patient's state.

PMID- 29197826
TI  - Effects of host cell sterol composition upon internalization of Yersinia
      pseudotuberculosis and clustered beta1 integrin.
AB  - Yersinia pseudotuberculosis is a foodborne pathogenic bacterium that causes acute
      gastrointestinal illness, but its mechanisms of infection are incompletely
      described. We examined how host cell sterol composition affected Y.
      pseudotuberculosis uptake. To do this, we depleted or substituted cholesterol in
      human MDA-MB-231 epithelial cells with various alternative sterols. Decreasing
      host cell cholesterol significantly reduced pathogen internalization. When host
      cell cholesterol was substituted with various sterols, only desmosterol and 7
      dehydrocholesterol supported internalization. This specificity was not due to
      sterol dependence of bacterial attachment to host cells, which was similar with
      all sterols studied. Because a key step in Y. pseudotuberculosis internalization
      is interaction of the bacterial adhesins invasin and YadA with host cell beta1
      integrin, we compared the sterol dependence of wildtype Y. pseudotuberculosis
      internalization with that of Deltainv, DeltayadA, and DeltainvDeltayadA mutant
      strains. YadA deletion decreased bacterial adherence to host cells, whereas
      invasin deletion had no effect. Nevertheless, host cell sterol substitution had a
      similar effect on internalization of these bacterial deletion strains as on the
      wildtype bacteria. The DeltainvDeltayadA double mutant adhered least to cells and
      so was not significantly internalized. The sterol structure dependence of Y.
      pseudotuberculosis internalization differed from that of endocytosis, as
      monitored using antibody-clustered beta1 integrin and previous studies on other
      proteins, which had a more permissive sterol dependence. This study suggests that
      agents could be designed to interfere with internalization of Yersinia without
      disturbing endocytosis.

PMID- 29197827
TI  - Intermediate-Term Risk of Stroke Following Cardiac Procedures in a Nationally
      Representative Data Set.
AB  - BACKGROUND: Studies on stroke risk following cardiac procedures addressed only
      perioperative and long-term risk following limited higher-risk procedures, were
      poorly generalizable, and often failed to stratify by stroke type. We calculated
      stroke risk in the intermediate risk period following cardiac procedures compared
      with common noncardiac surgeries and medical admissions. METHODS AND RESULTS: The
      Nationwide Readmissions Database contains readmission data for 49% of US
      admissions in 2013. We compared age-adjusted stroke readmission rates up to 90
      days postdischarge. We used Cox regression to calculate hazard ratios, up to 1
      year, of stroke risk comparing transcatheter aortic valve replacement versus
      surgical aortic valve replacement and coronary artery bypass graft versus
      percutaneous coronary intervention. Procedures and diagnoses were identified by
      International Classification of Disease, Ninth Revision, Clinical Modification
      codes. After cardiac procedures, 90-day ischemic stroke readmission rate was
      highest after transcatheter aortic valve replacement (2.05%); 90-day hemorrhagic
      stroke rate was highest after left ventricular assist device placement (0.09%).
      The hazard ratio for ischemic stroke after transcatheter aortic valve
      replacement, compared with surgical aortic valve replacement, in fully adjusted
      Cox models was 1.86 (95% confidence interval, 1.12-3.08; P=0.016) and 6.17 (95%
      confidence interval, 1.97-19.33; P=0.0018) for hemorrhagic stroke. There was no
      difference between coronary artery bypass graft and percutaneous coronary
      intervention. CONCLUSIONS: We demonstrated elevated readmission rates for
      ischemic and hemorrhagic stroke in the intermediate 30-, 60-, and 90-day risk
      periods following common cardiac procedures. Furthermore, we found an elevated
      risk of stroke after transcatheter aortic valve replacement compared with
      surgical aortic valve replacement up to 1 year.

PMID- 29197828
TI  - Matrine-Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive
      Oxygen Species-Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In
      Vitro by Targeting MKK3 and p38MAPK Signaling.
AB  - BACKGROUND: The matrine-type alkaloids are bioactive components extracted from
      Sophora flavescens, which is used in treatment of diabetes mellitus in
      traditional Chinese medicine. Advanced glycation end products mediate diabetic
      vascular complications. This study was aimed to investigate the protective
      effects and molecular mechanisms of matrine-type alkaloids on advanced glycation
      end products-induced reactive oxygen species-mediated endothelial apoptosis.
      METHODS AND RESULTS: Rats aorta and cultured rat aortic endothelial cells were
      exposed to advanced glycation end products. Matrine-type alkaloids, p38 mitogen
      activated protein kinase (MAPK) inhibitor, and small interference RNAs against
      p38 MAPK kinases MAPK kinase kinase (MKK)3 and MKK6 were administrated.
      Intracellular reactive oxygen species production, cell apoptosis, phosphorylation
      of MKKs/p38 MAPK, and expression levels of heme oxygenase/NADPH quinone
      oxidoreductase were assessed. The nuclear factor erythroid 2-related factor 2
      nuclear translocation and the binding activity of nuclear factor erythroid 2
      related factor 2 with antioxidant response element were also evaluated. Matrine
      type alkaloids suppressed intracellular reactive oxygen species production and
      inhibited endothelial cell apoptosis in vivo and in vitro by recovering
      phosphorylation of MKK3/6 and p38 MAPK, nuclear factor erythroid 2-related factor
      2 nuclear translocation, and antioxidant response element binding activity, as
      well as the expression levels of heme oxygenase/NADPH quinone oxidoreductase. p38
      MAPK inhibitor treatment impaired the effects of matrine-type alkaloids in vivo
      and in vitro. MKK3/6 silencing impaired the effects of matrine-type alkaloids in
      vitro. CONCLUSIONS: Matrine-type alkaloids exert endothelial protective effects
      against advanced glycation end products induced reactive oxygen species-mediated
      apoptosis by targeting MKK3/6 and enhancing their phosphorylation.

PMID- 29197829
TI  - Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke.
AB  - BACKGROUND: Exposure to cadmium has been associated with carotid plaques,
      inflammation in carotid plaques, and increased risk of ischemic stroke. This
      study examined the separate and interacting effects of blood cadmium levels and
      carotid plaques on the risk of incident ischemic stroke. METHODS AND RESULTS:
      Cadmium levels were measured in 4156 subjects (39.2% men; mean+/-SD age 57.3+/
      5.9 years) without history of stroke, from the Malmo Diet and Cancer cohort. The
      right carotid artery was examined using B-mode ultrasound examination at
      baseline. Incidence of ischemic stroke was monitored over a mean follow-up of
      16.7 years. Carotid plaque was present in 34.5% of participants. Cadmium was
      significantly higher in subjects with plaque (mean+/-SD: 0.53+/-0.58 MUg/L versus
      0.42+/-0.49 MUg/L; P<0.001). A total of 221 subjects had ischemic stroke during
      the follow-up. Incidence of ischemic stroke was associated both with carotid
      plaque (hazard ratio 1.44, 95% confidence interval, 1.09-1.90, P=0.009) and
      cadmium (hazard ratio for quartile [Q] 4 versus Q1-3: 1.95, confidence interval,
      1.33-2.85, P=0.001), after adjustment for risk factors. There was a significant
      interaction between cadmium and plaque with respect to risk of ischemic stroke
      (P=0.011). Adjusted for risk factors, subjects with plaque and cadmium in Q4 had
      a hazard ratio of 2.88 (confidence interval, 1.79-4.63) for ischemic stroke,
      compared with those without plaque and cadmium in Q1 to Q3. CONCLUSIONS: Cadmium
      was associated with incidence of ischemic stroke, both independently and in
      synergistic interaction with carotid plaques. This supports the hypothesis that
      cadmium promotes vulnerability of carotid plaques, thereby increasing the risk of
      rupture and ischemic stroke.

PMID- 29197831
TI  - Association Between Smoking and Serum GlycA and High-Sensitivity C-Reactive
      Protein Levels: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian
      Longitudinal Study of Adult Health (ELSA-Brasil).

PMID- 29197830
TI  - Association of Accelerometry-Measured Physical Activity and Cardiovascular Events
      in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and
      Independence for Elders) Study.
AB  - BACKGROUND: Data are sparse regarding the value of physical activity (PA)
      surveillance among older adults-particularly among those with mobility
      limitations. The objective of this study was to examine longitudinal associations
      between objectively measured daily PA and the incidence of cardiovascular events
      among older adults in the LIFE (Lifestyle Interventions and Independence for
      Elders) study. METHODS AND RESULTS: Cardiovascular events were adjudicated based
      on medical records review, and cardiovascular risk factors were controlled for in
      the analysis. Home-based activity data were collected by hip-worn accelerometers
      at baseline and at 6, 12, and 24 months postrandomization to either a physical
      activity or health education intervention. LIFE study participants (n=1590; age
      78.9+/-5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of
      experiencing a subsequent cardiovascular event per 500 steps taken per day based
      on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96;
      P=0.001). At baseline, every 30 minutes spent performing activities >=500 counts
      per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were
      also associated with a lower incidence of cardiovascular events. Throughout
      follow-up (6, 12, and 24 months), both the number of steps per day (per 500
      steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration
      of activity >=500 counts per minute (per 30 minutes; hazard ratio, 0.76;
      confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with
      lower cardiovascular event rates. CONCLUSIONS: Objective measurements of physical
      activity via accelerometry were associated with cardiovascular events among older
      adults with limited mobility (summary score >10 on the Short Physical Performance
      Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

PMID- 29197832
TI  - Comparison of Deep Sedation With General Anesthesia in Patients Undergoing
      Percutaneous Mitral Valve Repair.
AB  - BACKGROUND: Percutaneous edge-to-edge mitral valve repair (PMVR) has become an
      established treatment option for mitral regurgitation in patients not eligible
      for surgical repair. Currently, most procedures are performed under general
      anesthesia (GA). An increasing number of centers, however, are performing the
      procedure under deep sedation (DS). Here, we compared patients undergoing PMVR
      with GA or DS. METHODS AND RESULTS: A total of 271 consecutive patients underwent
      PMVR at our institution between May 2014 and December 2016. Seventy-two
      procedures were performed under GA and 199 procedures under DS. We observed that
      in the DS group, doses of propofol (743+/-228 mg for GA versus 369+/-230 mg for
      DS, P<0.001) and norepinephrine (1.1+/-1.6 mg for GA versus 0.2+/-0.3 mg for DS,
      P<0.001) were significantly lower. Procedure time, fluoroscopy time, and dose
      area product were significantly higher in the GA group. There was no significant
      difference between GA and DS with respect to overall bleeding complications,
      postinterventional pneumonia (4% for GA versus 5% for DS), or C-reactive protein
      levels (361+/-351 nmol/L for GA versus 278+/-239 nmol/L for DS). Significantly
      fewer patients with DS needed a postinterventional stay in the intensive care
      unit (96% for GA versus 19% for DS, P<0.001). Importantly, there was no
      significant difference between DS and GA regarding intrahospital or 6-month
      mortality. CONCLUSIONS: DS for PMVR is safe and feasible. No disadvantages with
      respect to procedural outcome or complications in comparison to GA were observed.
      Applying DS may simplify the PMVR procedure.

PMID- 29197833
TI  - Prehospital intravenous access for survival from out-of-hospital cardiac arrest:
      propensity score matched analyses from a population-based cohort study in Osaka,
      Japan.
AB  - OBJECTIVES: Prehospital intravenous access is a common intervention for patients
      with out-of-hospital cardiac arrest (OHCA). We aimed to assess the effectiveness
      of prehospital intravenous access and subsequent epinephrine administration on
      outcomes among OHCA patients. METHODS: We conducted a prospective cohort study of
      patients with OHCA from non-traumatic causes aged >=18 years in Osaka, Japan from
      January 2005 through December 2012. The primary outcome was 1-month survival with
      favourable neurological outcome defined as a cerebral performance category of 1
      or 2. The association between intravenous line placement and survival with
      favourable neurological outcome was evaluated by logistic regression, after
      propensity score matching for the intravenous access attempt stratified by
      initial documented rhythm of ventricular fibrillation (VF) or non-VF. The
      contribution of epinephrine administration to the outcome was also explored.
      RESULTS: Among OHCA patients during the study period, 3208 VF patients and 38 175
      non-VF patients were included in our analysis. Intravenous access attempt was
      negatively associated with 1-month survival with a favourable neurological
      outcome in VF group (OR 0.76, 95% CI 0.59 to 0.98), while no association was
      observed in the non-VF group (OR 1.06, 95% CI 0.84 to 1.34). Epinephrine
      administration had no positive association in the VF patients (OR 0.75, 95% CI
      0.51 to 1.07) and positively associated in the non-VF patients (OR 1.52, 95% CI
      1.08 to 2.08) with the favourable neurological outcome. CONCLUSIONS: Intravenous
      access attempt could be negatively associated with survival with a favourable
      neurological outcome after OHCA. Subsequent epinephrine administration might be
      effective for non-VF OHCAs.

PMID- 29197834
TI  - Study protocol for statin web-based investigation of side effects (StatinWISE): a
      series of randomised controlled N-of-1 trials comparing atorvastatin and placebo
      in UK primary care.
AB  - INTRODUCTION: Statins are effective at preventing cardiovascular disease, widely
      prescribed and their use is growing. Uncertainty persists about whether they
      cause symptomatic muscle adverse effects, such as pain and weakness, in the
      absence of statin myopathy. Discrepancies between data from observational
      studies, which suggest statins are associated with excess muscle symptoms, and
      from randomised trials, which suggest no such excess, have caused confusion. N-of
      1 trials offer the opportunity to establish whether muscle symptoms during statin
      use are caused by statins in particular individuals. METHODS AND ANALYSIS: This
      series of 200 randomised, double-blinded N-of-1 trials in primary care will
      determine (1) the effect of statins on all muscle symptoms and (2) the effect of
      statins on muscle pain that is perceived to be statin related. Patients who are
      considering discontinuing statin use due to muscle symptoms and those who have
      discontinued in the last 3 years due to such symptoms will be recruited.
      Participants will be randomised to a sequence of six 2-month treatment periods
      during which they will receive atorvastatin 20 mg per day or matched placebo. On
      each of the last 7 days of each treatment period, participants will rate their
      muscle symptoms on a Visual Analogue Scale (VAS).At the end of their trial,
      participants will be shown numerical and graphical summaries of their own symptom
      data during statin and placebo periods. The primary analysis on the aggregate
      data from all participants will be a linear mixed model for VAS muscle symptom
      score, comparing scores during treatment with statin and placebo. ETHICS AND
      DISSEMINATION: This trial received a favourable opinion from South Central
      Hampshire A Research Ethics Committee. Results will be published in a peer
      reviewed medical journal. Dissemination of results to patients will take place
      via the media, website (statinwise.lshtm.ac.uk) and patient organisations. TRIAL
      REGISTRATION NUMBER: ISRCTN30952488.

PMID- 29197835
TI  - Kombucha: is a cup of tea good for you?
AB  - A 54-year-old asthmatic woman presented to hospital with a 10-day history of
      breathlessness. On examination, she was tachypnoeic with mild wheeze. She had
      preserved peak flows and was saturating at 100% on room air. Investigations
      revealed severe metabolic lactic acidosis. On further questioning, it transpired
      that she drank kombucha tea, which has been linked to lactic acidosis. She made a
      full recovery with supportive management and cessation of the tea.

PMID- 29197836
TI  - Systemic lupus erythematosus (SLE): an unusual cause of ileocolic
      intussusception.
AB  - Intussusception is a rare diagnosis in adults. Gastrointestinal involvement is
      not unusual in systemic lupus erythematosus (SLE).1 A case of intussusception as
      first presenting symptom of SLE is described. A 50-year-old woman of Chinese
      origin came to the emergency room with symptoms of high fever, nausea, vomiting
      and weight loss of 10 kg. Three months before, an episode with abdominal pain due
      to ileal invagination in the colon occurred. Laboratory analysis showed:
      thrombocytopaenia, lymphopaenia, positive antinuclear antibody, antidouble
      stranded DNA, Coombs tests and low C3 in combination with an active urine
      sediment and proteinuria. CT and positron emission tomography scan showed
      lymphadenopathy, but no other abnormalities. Axillar lymph node biopsy showed no
      abnormalities. The diagnosis new-onset SLE was made. Prednisone treatment was
      started and soon thereafter tapered, azathioprine and hydroxychloroquine were
      added. During follow-up, the SLE remained in remission. SLE is a rare cause of
      ileocolic intussusception and ileocolic intussusception may be the first
      presenting symptom.

PMID- 29197837
TI  - Bilateral ocular surface squamous neoplasia with bilateral periocular basal cell
      carcinoma in a case of xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive disorder associated with
      multiple oculocutaneous manifestations.We discuss a unique case of XP having
      bilateral ocular surface squamous neoplasia (OSSN) and periocular basal cell
      carcinoma. In the right eye, a large OSSN mass involving the ocular surface
      extensively along with intraocular invasion was noted, whereas in the left eye,
      the tumour mass was involving the limbus, and extending up to three clock hours.
      Because of extensive disease in the right eye, orbital exenteration was
      performed, and for the left eye, a wide excision of the mass with triple freeze
      thaw cryo application to the margins followed by amniotic membrane grafting was
      done. Basal cell carcinoma was noted around the medial canthus on both sides. The
      right-sided basal cell carcinoma was treated by wide excision followed by a
      forehead rotation flap and the left-sided lesion was managed with topical 5%
      imiquimod cream.

PMID- 29197838
TI  - Leg length discrepancy: the importance of a complete history and examination.
AB  - A 26-year-old woman with a 1-year history of right knee pain had failed to
      respond to analgesia and activity modification in the community. Her general
      practitioner referred her to the orthopaedic department for specialist review. A
      thorough history revealed that she had multiple orthopaedic interventions as a
      child. The patient had significant postoperative infection of the left knee
      following knee surgery at 7 years of age. Examination demonstrated the presence
      of a limp, scoliosis and suspected leg length discrepancy. Plain film radiography
      confirmed the presence of leg length discrepancy, with the right limb measuring
      30 mm longer than the left. The leg length discrepancy was likely secondary to a
      growth arrest of the left knee following the postoperative infection in
      childhood. The patient was managed with physiotherapy and heel raises and
      received regular orthopaedic follow-up.

PMID- 29197839
TI  - Rupture of the posterior cul-de-sac during trial of labour after caesarean
      section.
AB  - Rupture of the vaginal wall in unobstructed labour is a rare entity in the
      developed world. This case report describes rupture of the posterior cul-de-sac
      in a healthy 34-year-old multiparous woman attempting trial of labour after
      caesarean section. The woman presented to the labour ward at term with
      spontaneous onset of contractions. In the second stage of labour, the woman
      experienced sudden severe abdominal pain, different in character from the
      contraction pain. Therefore, the baby was delivered by ventouse extraction. As
      the woman continued to experience severe immobilising abdominal pain during the
      hospital stay, a CT scan was performed which revealed a haematoma and free fluid
      at the right side of the uterus. A laparotomy was performed 3 days postdelivery,
      during which a rupture of the posterior cul-de-sac was found and closed with a
      continuous suture. The woman was discharged 3 days after laparotomy in good
      clinical condition.

PMID- 29197840
TI  - The telescoping aorta: a case of circumferential aortic dissection with intimo
      intimal intussusception into the left ventricle.

PMID- 29197841
TI  - Haemorrhagic conversion of infectious myelitis in an immunocompromised patient.
AB  - A 28-year-old man recently diagnosed with HIV (CD4 19 cells/mm3, viral load 3.6
      million copies/mL, not on highly active antiretroviral therapy on initial
      diagnosis at outside hospital), disseminated histoplasmosis, shingles and
      syphilis presented with paraplegia developing over 3 days. Spine MRI demonstrated
      a longitudinally extensive cord lesion extending from C3 to the tip of the conus.
      Brain MRI was consistent with meningoencephalitis. Cerebrospinal fluid findings
      were notable for positive varicella zoster virus (VZV) and cytomegalovirus (CMV)
      PCRs as well as a Venereal Disease Research Laboratory titre of 1:2. Patient was
      started on treatment for VZV and CMV meningoencephalitis, neurosyphilis and high
      dose steroids for infectious myelitis. Repeat spine MRI demonstrated subacute
      intramedullary haemorrhage of the cervical cord. He was ultimately discharged to
      a skilled nursing facility for long-term intravenous antiviral therapy and
      rehabilitation. After 59 days in the hospital, his neurological exam remained
      grossly unchanged, with flaccid paraplegia and lack of sensation to fine touch in
      his lower extremities.

PMID- 29197842
TI  - Angiomatosis of the uterus, cervix and fallopian tubes: a rare and benign cause
      of intractable, heavy menstrual bleeding.
AB  - Angiomatosis of the uterus, cervix and fallopian tubes is a rare and benign
      entity that has not been reported in the literature previously. We present a case
      of a 27-year-old patient with severe and intractable heavy menstrual bleeding
      unresponsive to all conservative and conventional forms of treatment. Following a
      laparoscopic hysterectomy, the histopathological finding of angiomatosis, a
      vascular abnormality in the uterus, cervix and fallopian tubes, provided a
      plausible explanation in this situation.

PMID- 29197843
TI  - Carcinoma en cuirasse.
AB  - We present a case of carcinoma en cuirasse as a presentation of advanced lobular
      breast carcinoma. On further investigation, she was found to have metastasis to
      her liver and bone. We report this case to highlight the phenomenon of cutaneous
      metastasis. It is important to consider this diagnosis as an initial
      manifestation of breast cancer, but rarely, it can also be associated with other
      adenocarcinomas, for example, carcinoma of lung, kidney or gastrointestinal
      tract.

PMID- 29197844
TI  - Volvulus of a wandering pelvic spleen: CT diagnosis with 3D reformatted
      illustration.

PMID- 29197845
TI  - Neck mass: an obstructive cause of respiratory distress with medical management.
AB  - Congenital goitre is a known cause of hypothyroidism in newborn. Congenital
      goitre can be due to defective synthesis of thyroxine or administration of
      antithyroid drugs to the mother during pregnancy. In this case report, we report
      an instance of a preterm male infant with antenatally detected goitre presenting
      as a neck mass with congenital hypothyroidism. Hormonal replacement therapy was
      started immediately after birth which lead to resolution of the mass and
      normalisation of thyroid function.

PMID- 29197846
TI  - Severe recurrent hypothermia in an elderly patient with refractory mania
      associated with atypical antipsychotic, valproic acid and oxcarbazepine therapy.
AB  - Hypothermia is a rare but serious condition that has been associated with various
      psychiatric medications. We present a 76-year-old woman with refractory mania who
      developed multiple episodes of severe hypothermia associated with several
      psychiatric medications including olanzapine, quetiapine, valproic acid and
      oxcarbazepine. These episodes resolved following discontinuation of the agents.
      The patient had never experienced hypothermia before, despite having been on
      these or similar agents for many years. With traditional treatments for mania not
      feasible, other medications were used to treat her including lithium, clonazepam,
      gabapentin and the novel protein kinase c inhibitor tamoxifen. The regimen
      resulted in some success and importantly, without triggering hypothermia. This
      case alerts clinicians to the rare side effect of hypothermia in response to
      various psychiatric medications, the fact that patients can suddenly develop this
      intolerance and suggests possible medications that may be used safely without
      triggering hypothermia.

PMID- 29197847
TI  - Perforated neuroenteric cyst masquerading as congenital pulmonary airway
      malformation.
AB  - A 3-month-old child was presented with haemoptysis with respiratory distress.
      Imaging was suggestive of a cavitary lesion in the lung with surrounding
      consolidation. Diagnosis of a primary lung pathology like congenital pulmonary
      airway malformation was considered. Based on clinical suspicion and prior
      experience, a Tc-99m pertechnetate radionuclide study was performed, which
      clinched the diagnosis of foregut duplication cyst. Intraoperative findings
      confirmed the presence of a neuroenteric cyst. The child remains asymptomatic on
      follow-up awaiting neurosurgical intervention for the intraspinal component of
      the cyst.

PMID- 29197848
TI  - Challenging and uncommon diagnosis of long-evolution ascites.
AB  - This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No
      history of liver disease or asbestos exposure. He complained of ascites during
      the last 3 years with worsening in the last year with severe ascites development.
      Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil
      count >250 cells/uL. Ascitic fluid cytology revealed reactive mesothelial
      hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose
      positron emission tomography/CT showed 'omental cake' pattern suggesting
      peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop
      adhesions and necrosis with whitish exudate in the right pelvic excavation.
      Biochemical/cytological/histological/microbiological study only revealed reactive
      mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A
      second exploratory laparoscopy with liver and peritoneal biopsies and
      appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary
      mesothelioma. The patient was referred for intraperitoneal chemotherapy and is
      undergoing monthly therapeutic paracentesis.

PMID- 29197849
TI  - Retrovesical malignant fibrous histiocytoma: a rare tumor.
AB  - Malignant fibrous histiocytoma (MFH) originating from the retrovesical space is a
      very rare tumour. A 61-year-old man presented to our hospital with complaints of
      retention of urine and burning sensation during micturition since 6 months. CT
      scan abdomen showed a large retrovesical mass between the urinary bladder and
      rectum, measuring 11*9*12 cm, displacing the urinary bladder. Serum PSA (Prostate
      Specific Antigen) value was within normal range. Biopsy from retrovesical mass
      and immunohistochemistry was suggestive of MFH. Wide excision of the retrovesical
      mass was done. Histopathology confirmed the diagnosis of MFH. He received
      adjuvant radiotherapy. He is on regular follow-up since the last 2 years after
      radiotherapy with no signs and symptoms of disease recurrence.

PMID- 29197850
TI  - Preoperative simulation unveiled undetected surgical difficulties in a case of
      cochlear implantation.
AB  - We herein report a case in which extensive preparation changed a difficult-to
      treat patient into an easy one. We performed a revision cochlear implantation on
      a patient whose first procedure had been aborted due to unidentified
      difficulties. During a series of thorough three-dimensional simulations, we found
      that the patient in question had a normal cochlea but the cochlea was placed in
      an unusual position and orientation. This condition is difficult to detect on
      standard preoperative radiographic images. Through this simulation, we were able
      to propose a surgical plan to avoid making the same mistakes as the first
      surgeon. We present this case not as a rare difficult case of an unfortunate
      patient but instead emphasise the importance of performing surgical simulation
      and looking for non-obvious difficulties. This case is an example of the success
      that can be achieved with such extensive preparation.

PMID- 29197851
TI  - Deadly combination: Clostridium septicum and colorectal malignancy.
AB  - Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal
      malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This
      case outlines an initial presentation of colonic malignancy as gas gangrene from
      C.septicum infection.A 69-year-old man presented with abdominal pain, vomiting
      and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was
      elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed
      caecal thickening and subcutaneous emphysema overlying the left flank.
      Clinically, he became haemodynamically unstable. Examination revealed crepitus
      overlying the left flank in keeping with gas gangrene. The patient required
      immediate surgical debridement. Tissue specimens cultured C.septicum Following a
      complicated postoperative period, he was transferred to the plastic surgery team
      for further tissue debridement and reconstruction. A colonoscopy was later
      performed which was suspicious for malignancy. Colorectal multidisciplinary team
      discussion is awaited.

PMID- 29197852
TI  - Artery of Percheron ischaemic stroke revealed by brain MRI DWI/ADC sequences.

PMID- 29197853
TI  - Atrial myxoma: an unusual aetiology for exertional dyspnoea and palpitation.

PMID- 29197854
TI  - Nivolumab-induced polyarthritis.

PMID- 29197855
TI  - Detection of genome-wide copy number variants in myeloid malignancies using next
      generation sequencing.
AB  - AIMS: Genetic abnormalities, including copy number variants (CNV), copy number
      neutral loss of heterozygosity (CN-LOH) and gene mutations, underlie the
      pathogenesis of myeloid malignancies and serve as important diagnostic,
      prognostic and/or therapeutic markers. Currently, multiple testing strategies are
      required for comprehensive genetic testing in myeloid malignancies. The aim of
      this proof-of-principle study was to investigate the feasibility of combining
      detection of genome-wide large CNVs, CN-LOH and targeted gene mutations into a
      single assay using next-generation sequencing (NGS). METHODS: For genome-wide CNV
      detection, we designed a single nucleotide polymorphism (SNP) sequencing backbone
      with 22 762 SNP regions evenly distributed across the entire genome. For targeted
      mutation detection, 62 frequently mutated genes in myeloid malignancies were
      targeted. We combined this SNP sequencing backbone with a targeted mutation
      panel, and sequenced 9 healthy individuals and 16 patients with myeloid
      malignancies using NGS. RESULTS: We detected 52 somatic CNVs, 11 instances of CN
      LOH and 39 oncogenic mutations in the 16 patients with myeloid malignancies, and
      none in the 9 healthy individuals. All CNVs and CN-LOH were confirmed by SNP
      microarray analysis. CONCLUSIONS: We describe a genome-wide SNP sequencing
      backbone which allows for sensitive detection of genome-wide CNVs and CN-LOH
      using NGS. This proof-of-principle study has demonstrated that this strategy can
      provide more comprehensive genetic profiling for patients with myeloid
      malignancies using a single assay.

PMID- 29197857
TI  - Corrigendum to: Interleukin-33 plasma levels in patients with relapsing-remitting
      multiple sclerosis.

PMID- 29197856
TI  - Comparison of haemoglobin assessments by HemoCue and two automated haematology
      analysers in young Laotian children.
AB  - BACKGROUND: Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia
      screening in both adults and children. However, few studies have compared the
      diagnostic accuracy of Hemocue with an automated haematology analyser in young
      children. AIM: To compare Hb concentrations by Hemocue Hb301 and two automated
      haematology analysers in young children in rural communities of Lao PDR. METHODS:
      Capillary blood was collected from 6-month-old to 23-month-old children (n=1487)
      for determination of Hb concentration by Hemocue Hb301. On the same day, venous
      blood was collected for complete blood count using one of two haematology
      analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In
      a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301.
      Agreement between the two methods was estimated using Bland-Altman plots.
      RESULTS: Mean capillary Hb by Hemocue was significantly higher than mean venous
      Hb by haematology analysers combined (108.4+/-10.3 g/L vs 102.3+/-13.1 g/L;
      P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by
      Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement
      showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean
      venous Hb concentration by Hemocue Hb301 (113.6+/-14.0 g/L) was significantly
      higher than mean capillary Hb concentration by Hemocue Hb301 (110.0+/-10.7;
      P=0.03 g/L), which in turn was significantly higher than mean venous Hb
      concentration by the Mindray BC-3000Plus (102.3+/-17.4 g/L). CONCLUSION:
      Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor
      agreement compared with venous Hb by automated haematology analysers, resulting
      in significantly different anaemia prevalences.

PMID- 29197858
TI  - Image-based 3D surface approximation of the bladder using structure-from-motion
      for enhanced cystoscopy based on phantom data.
AB  - Bladder cancer is likely to recur after resection. For this reason, bladder
      cancer survivors often undergo follow-up cystoscopy for years after treatment to
      look for bladder cancer recurrence. 3D modeling of the bladder could provide more
      reliable cystoscopic documentation by giving an overall picture of the organ and
      tumor positions. However, 3D reconstruction of the urinary bladder based on
      endoscopic images is challenging. This is due to the small field of view of the
      endoscope, considerable image distortion, and occlusion by urea, blood or
      particles. In this paper, we will demonstrate a method for the conversion of
      uncalibrated, monocular, endoscopic videos of the bladder into a 3D model using
      structure-from-motion (SfM). First of all, frames are extracted from video
      sequences. Distortions are then corrected in a calibration procedure. Finally,
      the 3D reconstruction algorithm generates a sparse surface approximation of the
      bladder lining based on the corrected frames. This method was tested using an
      endoscopic video of a phantom that mimics the rich structure of the bladder. The
      reconstructed 3D model covered a large part of the object, with an average
      reprojection error of 1.15 pixels and a relative accuracy of 99.4%.

PMID- 29197859
TI  - Evaluation of the Aptima HBV Quant assay vs. the COBAS TaqMan HBV test using the
      high pure system for the quantitation of HBV DNA in plasma and serum samples.
AB  - BACKGROUND: Proper management of patients with chronic hepatitis B virus (HBV)
      infection requires monitoring of plasma or serum HBV DNA levels using a highly
      sensitive nucleic acid amplification test. Because commercially available assays
      differ in performance, we compared herein the performance of the Hologic Aptima
      HBV Quant assay (Aptima) to that of the Roche Cobas TaqMan HBV test for use with
      the high pure system (HPS/CTM). METHODS: Assay performance was assessed using HBV
      reference panels as well as plasma and serum samples from chronically HBV
      infected patients. Method correlation, analytical sensitivity,
      precision/reproducibility, linearity, bias and influence of genotype were
      evaluated. Data analysis was performed using linear regression, Deming
      correlation analysis and Bland-Altman analysis. RESULTS: Agreement between the
      assays for the two reference panels was good, with a difference in assay values
      vs. target <0.5 log. Qualitative assay results for 159 clinical samples showed
      good concordance (88.1%; kappa=0.75; 95% confidence interval: 0.651-0.845). For
      the 106 samples quantitated by both assays, viral load results were highly
      correlated (R=0.92) and differed on average by 0.09 log, with 95.3% of the
      samples being within the 95% limit of agreement of the assays. Linearity for
      viral loads 1-7 log was excellent for both assays (R2>0.98). The two assays had
      similar bias and precision across the different genotypes tested at low viral
      loads (25-1000 IU/mL). CONCLUSIONS: Aptima has a performance comparable with that
      of HPS/CTM, making it suitable for use for HBV infection monitoring. Aptima runs
      on a fully automated platform (the Panther system) and therefore offers a
      significantly improved workflow compared with HPS/CTM.

PMID- 29197860
TI  - Obesity is associated with vitamin D deficiency in Danish children and
      adolescents.
AB  - BACKGROUND: Sufficient serum concentrations of vitamin D are required to maintain
      bone health during growth. The aims of this study were to determine whether
      vitamin D deficiency is more prevalent among children and adolescents with
      obesity compared to their normal weight peers and to identify clinical and
      biochemical variables associated with vitamin D deficiency. METHODS: One thousand
      four hundred and eighty-four children and adolescents with overweight/obesity and
      2143 population-based controls were recruited from the Danish Childhood Obesity
      Biobank. Anthropometric variables and fasting concentrations of serum 25-hydroxy
      vitamin D (25-OH-D), plasma parathyroid hormone (PTH), calcium and phosphate were
      assessed at baseline. Vitamin D deficiency was defined as serum 25-OH-D
      concentrations <30 nmol/L. Linear and logistic regressions were used to identify
      variables associated with vitamin D deficiency. RESULTS: A total of 16.5% of the
      children and adolescents with obesity (body mass index [BMI] standard deviation
      score [SDS]>2.33) exhibited vitamin D deficiency, with an odds ratio (OR) 3.41
      (confidence interval [CI]: 2.27-5.71; p<0.0001) for being vitamin D deficient
      compared to their normal weight peers. BMI-SDS was independently and inversely
      associated with serum 25-OH-D concentrations. Other independent risk factors for
      vitamin D deficiency were being older than 14 years (OR: 2.39; CI: 1.28-4.48;
      p=0.006), more than 4 daily hours of screen time (OR: 4.56; CI: 2.59-8.05;
      p<0.0001) and blood sample assessment during winter-spring (OR: 6.44; CI: 4.47
      9.26; p<0.0001). CONCLUSIONS: Vitamin D deficiency was common among Danish
      children and adolescents with obesity. The degree of obesity was independently
      associated with lower serum 25-OH-D concentrations.

PMID- 29197861
TI  - Short-term adverse effects of testosterone used for priming in prepubertal boys
      before growth hormone stimulation test.
AB  - BACKGROUND: Despite the fact that priming with sex steroids in prepubertal
      children before growth hormone (GH) provocative tests is recommended, there is an
      ongoing controversial discussion about the appropriate age of the children, the
      drug used for priming, the dose and the period between priming and the GH test.
      Interestingly, there is no discussion on the safety of this procedure. To date,
      only little data have been available on the possible side effects of priming with
      testosterone. METHODS: We analyzed the outcome in 188 short-statured prepubertal
      boys who had been primed with testosterone enanthate (n=136: 50 mg; n=51: 125 mg,
      and accidentally one boy with 250 mg) 7 days prior to the GH test. Serum
      testosterone levels were measured on the day of the GH test in 99 boys. RESULTS:
      Overall, only five boys developed adverse side effects. Two boys (dose 125 mg)
      showed severe low-flow priapism and had to undergo decompression of the corpora
      cavernosa. One boy suffered from self-limiting priapism and testicular pain (dose
      50 mg). Two patients reported testicular pain (each dose 50 mg). The single
      patient with 250 mg testosterone did not show any adverse effects. The total side
      effect rate was 2.7%. The serum testosterone levels of the boys with side effects
      were not different from the testosterone levels of the boys without any side
      effects. CONCLUSIONS: Parents and patients should be informed about the possible
      side effects of priming with testosterone such as priapism and testicular pain.
      However, the overall side effect rate is low. We found no correlation between the
      outcome and the testosterone dose used and/or the level of serum testosterone.

PMID- 29197862
TI  - Monoterpenes induce the heat shock response in Arabidopsis.
AB  - Monoterpenes are common constituents of essential oils produced by plants.
      Although it has been reported that monoterpenes enhanced the heat tolerance of
      plants, the mechanism has not been elucidated. Here, we tested whether 13
      monoterpenes promoted the heat shock response (HSR) in Arabidopsis. To assess the
      HSR-inducing activity of monoterpenes, we produced transgenic Arabidopsis, which
      has the beta-glucuronidase gene driven by the promoter of a small heat shock
      protein (HSP17.6C-CI) gene. Results indicated that two monocyclic and four
      bicyclic monoterpenes showed HSR-inducing activities using the reporter gene
      system. In particular, (-)-perillaldehyde, which is a monocyclic monoterpene,
      demonstrated the most potent HSR-inducing activity. (-)-Perillaldehyde
      significantly inhibited the reduction of chlorophyll content by heat shock in
      Arabidopsis seedlings. Our previous study indicated that chemical HSR inducers
      such as geldanamycin and sanguinarine inhibited the activity of plant chaperones
      in vitro. (-)-Perillaldehyde also inhibited chaperone activity, indicating that
      it might promote the expression of heat shock protein genes by inhibiting
      chaperones in the plant cell.

PMID- 29197863
TI  - Proteomic Analysis Reveals Grb2 as a Key Regulator of Periodic Mechanical Stress
      Transduction in Chondrocytes.
AB  - BACKGROUND/AIMS: Periodic mechanical stress could significantly promote
      chondrocyte proliferation and matrix synthesis. However, the mechanisms
      underlying the ability of chondrocyte detecting and responding to periodic
      mechanical stimuli have not been well delineated. METHODS: Quantitative proteomic
      analysis was performed to construct the differently expressed proteome profiles
      of chondrocyte under pressure. Then a combination of Western blot, quantitative
      real-time PCR, lentiviral vector and histological methods were used to confirm
      the proteomic results and investigate the mechanoseing mechanism. RESULTS: Growth
      factor receptor-bound protein 2 (Grb2), a component of integrin adhesome, was
      found a 1.49-fold increase in dynamic stress group. This process was mediated
      through integrin beta1, leading to increased phosphorylation of focal adhesion
      kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2) respectively
      and then produce the corresponding biological effects. CONCLUSION: This was the
      first time to demonstrate Grb2 has such an important role in periodic
      mechanotransduction, and the proteomic data could facilitate the further
      investigation of chondrocytes mechanosensing.

PMID- 29197864
TI  - Biopsy-Free Prediction of Pathologic Type of Primary Nephrotic Syndrome Using a
      Machine Learning Algorithm.
AB  - BACKGROUND/AIMS: Renal biopsy is the gold standard to determine the pathologic
      type of primary nephrotic syndrome, which is critical for diagnosis, choice of
      treatment and evaluation of prognosis. However, in some cases, renal biopsy
      cannot be performed. METHODS: To explore the possibility of predicting the
      histology type of primary nephrotic syndrome without the need for biopsy, we
      trained and validated a machine learning algorithm using data from 222 patients
      with biopsy-confirmed primary nephrotic syndrome treated at our hospital between
      May 2008 and January 2016. The model was then tested prospectively on another
      sample of 63 patients with biopsy-confirmed primary nephrotic syndrome. RESULTS:
      Overall accuracy of prediction from the retrospective set of 222 patients was
      62.2% across all types of nephrotic syndrome. The accuracy of model prediction
      for the prospectively collected dataset of 63 patients was 61.9%. The algorithm
      identified 17 of 33 variables as contributing strongly to type of renal
      pathology. CONCLUSION: To our knowledge, this is the first such application of
      machine learning to predict the pathologic type of primary nephrotic syndrome,
      which may be clinically useful by itself as well as helpful for guiding future
      efforts at machine learning-based prediction in other disease contexts.

PMID- 29197865
TI  - Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and
      Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner.
AB  - BACKGROUND/AIMS: Osteosarcoma (OS) is the most common primary malignant tumor of
      bone tissue. Although treatment effectiveness has improved, the OS survival rate
      has fluctuated in recent years. Andrographolide (AG) has been reported to have
      antitumor activity against a variety of tumors. Our aim was to investigate the
      effects and potential mechanisms of AG in human osteosarcoma. METHODS: Cell
      viability and morphological changes were assessed by MTT and live/dead assays.
      Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase
      3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and
      western blot. Cell migration and invasion were detected by wound healing assay
      and Transwell(r) experiments. RESULTS: AG dose-dependently reduced the viability
      of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human
      OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate
      AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR
      and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the
      cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of
      OS, and this effect could be reversed with Beclin-1 siRNA. CONCLUSION: AG
      inhibits viability and induces autophagic death in OS cells. AG-induced autophagy
      inhibits the invasion and metastasis of OS.

PMID- 29197866
TI  - Proteomic Analysis Reveals a New Benefit of Periodic Mechanical Stress on
      Chondrocytes.
AB  - BACKGROUND/AIMS: In recent years, a variety of studies have been performed to
      investigate the cellular responses of periodic mechanical stress. In our previous
      studies, we found that periodic mechanical stress can promote proliferation and
      matrix synthesis through the integrin beta 1-mediated ERK1/2 pathway, and we used
      proteomic analysis to detect quantitative changes in chondrocytes under periodic
      mechanical stress. Despite these results, the effects and mechanisms of periodic
      mechanical stress are still not fully understood, so in this study we extended
      our study using phosphoproteomic techniques. METHODS: We used phosphoproteomic
      techniques to detect phosphorylation changes in chondrocytes under periodic
      mechanical stress and combined the results with the quantitative proteomic data
      to further explore the underlying mechanisms. Data were obtained by
      phosphorylation inhibition, quantitative real-time PCR (qPCR) analysis, western
      blot analysis and immunofluorescence assay. RESULTS: From phosphoproteomic
      analysis, a total of 1073 phosphorylated proteins and 2054 phosphopeptides were
      identified. The number of significant differentially expressed proteins and
      phosphopeptides was 97 and 108, respectively (ratio >1.20 or <0.83 at p<0.05).
      Periodic mechanical stress increased glycogen synthase kinase 3-beta (GSK3-beta)
      phosphorylation at Y216, promoted the phosphorylation of beta-catenin, decreased
      beta-catenin levels and suppressed the expression of type I collagen. In
      contrast, inhibition of GSK3-beta by TWS119, which specifically inhibits the
      phosphorylation of Y216, suppressed the phosphorylation of beta-catenin, which
      resulted in the accumulation of beta-catenin and an increase in the expression of
      type I collagen. CONCLUSIONS: We successfully constructed differentially
      expressed phosphoproteomic profiles of rat chondrocytes under periodic mechanical
      stress, and discovered a potential new therapeutic benefit in which periodic
      mechanical stress suppressed the formation of type I collagen in the matrix of
      chondrocytes via phosphorylation of GSK3-beta and beta-catenin.

PMID- 29197867
TI  - Topical Coconut Oil in Very Preterm Infants: An Open-Label Randomised Controlled
      Trial.
AB  - BACKGROUND: The immature fragile skin of preterm infants represents an inadequate
      protective barrier. The emollient and anti-infective properties of coconut oil
      make it a potentially beneficial topical agent for this population. OBJECTIVES:
      Our aim was to evaluate feasibility, safety, and the effects of topical coconut
      oil on skin condition in very preterm infants. METHODS: An open-label randomised
      controlled trial in preterm infants <30 weeks' gestation was conducted. Enrolled
      infants were randomised to receive either routine care or topical coconut oil (5
      mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin
      condition was the primary outcome, and was assessed using the Neonatal Skin
      Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil
      applications was recorded to assess clinical feasibility and all enrolled infants
      were monitored for adverse effects of topical coconut application, such as skin
      irritation. RESULTS: A total of 72 infants born <30 weeks' gestation were
      enrolled (36 infants per arm), with comparable demographic characteristics.
      Topical application of coconut oil was feasible and without adverse effects. The
      NSCS was maintained in the coconut oil group throughout the intervention period,
      but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in
      the control group (p = 0.01). There were no differences in common neonatal
      outcomes, including sepsis, necrotising enterocolitis, retinopathy of
      prematurity, chronic lung disease, and mortality. CONCLUSIONS: Topical coconut
      oil maintained a better skin condition in very preterm infants without adverse
      effects. This simple, safe, and affordable intervention warrants further
      investigation.

PMID- 29197868
TI  - The Dual Carboxymethyl Cellulase and Gelatinase Activities of a Newly Isolated
      Protein from Brevibacillus agri ST15c10 Confer Reciprocal Regulations in
      Substrate Utilization.
AB  - A protein showing endoglucanase-peptidase activity was prepared from a newly
      isolated bacterium (ST15c10). We identified ST15c10 as Brevibacillus agri based
      on electron-microscopic images and its 16S-rDNA sequence (GenBank accession No.
      HM446043), which exhibits 98.9% sequence identity to B. agri (KZ17)/B. formosus
      (DSM-9885T)/B. brevis. The enzyme was purified to homogeneity and gave a single
      peak during high-performance liquid chromatography on a Seralose 6B-150 gel
      matrix/C-18 column. MALDI-TOF mass-spectrometry and bioinformatics studies
      revealed significant similarity to M42-aminopeptidases/endoglucanases of the CelM
      family. These enzymes are found in all Brevibacillus strains for which the genome
      sequence is known. ST15c10 grows optimally on carboxymethyl cellulose (CMC)
      gelatin (40 degrees C/pH 8-9), and also shows strong growth/carboxymethyl
      cellulase (CMCase) activity in submerged bagasse fermentation. The purified
      enzyme also functions as endoglucanase with solid bagasse/rice straw. Its CMCase
      activity (optimal at pH 5.6 and 60 degrees C/Km = 35.5 uM/Vmax = 1,024U) was
      visualized by zymography on a CMC-polyacrylamide gel, which provided a strong
      band of approximately 70 kDa. The purified enzyme also showed strong peptidase
      (gelatinase) activity (pH 7.2/40 degrees C during zymography on 6-12% gelatin/1%
      gelatin-PAGE (at approx. 70 kDa). The CMCase activity is inhibited by the metal
      ions Mn/Cu/Fe/Co (50%), Hg/KMnO4 (100%), and by glucose or lactose (50-75%; all
      at 1 mM). The observed dose/time-dependent inhibition by Hg ions could be
      prevented with 2-mercaptoethanol. A comparison of the B. agri endoglucanase
      aminopeptidase (ELK43520; 350 aa) with other members of the M42-family revealed
      the conservation of active-site residues Cys256/Cys260, which were previously
      identified as metal-binding sites. Regulation of the endoglucanase activity
      probably occurs via metal binding-triggered changes in the redox state of the
      enzyme. Studies on this type of enzyme are of high importance for basic
      scientific and industrial research.

PMID- 29197869
TI  - Fibrocytes Ameliorate Acute Lung Injury by Decreasing Inflammatory Cytokine and
      Chemokine Levels and Reducing Neutrophil Accumulation in the Lung.
AB  - BACKGROUND/AIMS: Acute lung injury (ALI) remains a severe disease that threatens
      human life around the world. To decrease the mortality of ALI and improve ALI
      treatment efficacy, the development of more ALI treatments is urgently needed.
      Whether fibrocytes directly participate in ALI has not been studied. Therefore, a
      mouse model of ALI was induced with lipopolysaccharide (LPS). METHODS: Fibrocytes
      were harvested from peripheral blood mononuclear cells of bleomycin mice and
      identified by using flow cytometry to detect the expression of molecular makers.
      The fibrocytes were injected for the treatment of acute lung injury mice. The
      curative effects were evaluated by using ELISA to determine the cytokines
      (including TNF-alpha, IL-6 and IFN-gamma) concentrations in bronchoalveolar
      lavage fluid (BALF) supernatant. RESULTS: The concentrations of cytokines such as
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon
      gamma (IFN-gamma) were increased in mice with ALI induced with LPS. The
      concentrations of TNF-alpha, IL-6, and IFN-gamma as well as their mRNA and
      protein expression levels were decreased by administration of fibrocytes. The
      effect of fibrocytes in ameliorating ALI was time dependent. LPS treatment
      induced an increase in myeloperoxidase (MPO) activity, whereas the fibrocyte
      treatment caused inhibition of MPO activity as well as expression of the
      neutrophil-chemoattractant chemokine macrophage inflammatory protein 2 (MIP-2).
      CONCLUSION: Taken together, these data suggest that fibrocytes ameliorated ALI by
      suppressing inflammatory cytokines and chemokines as well as by decreasing the
      accumulation of neutrophils in the lung.

PMID- 29197870
TI  - Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent
      (BOLD) MRI.
AB  - BACKGROUND/AIMS: To date, there is no imaging technique to assess tubular
      function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD
      MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*).
      The present study investigates whether BOLD MRI can assess tubular function using
      a tubule-specific pharmacological maneuver. METHODS: Cross sectional study with
      28 participants including 9 subjects with ATN-induced acute kidney injury (AKI),
      9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS)
      with clamping of the renal artery serving as a model of ischemia/reperfusion
      (I/R)-induced subclinical ATN (median clamping time 15 min, no significant
      decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min
      after intravenous administration of 40 mg furosemide. RESULTS: Urinary neutrophil
      gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and
      NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before
      administration of furosemide, absolute medullary R2*, cortical R2*, and
      medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI
      vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys
      (p>0.05 each). Furosemide led to a significant decrease in the medullary and
      cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each),
      whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R
      kidneys (p>0.05 each). CONCLUSION: BOLD-MRI is able to detect even mild tubular
      injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking
      the Na+-K+-2Cl- transporter by furosemide.

PMID- 29197872
TI  - The Association of Circulating MiR-29b and Interleukin-6 with Subclinical
      Atherosclerosis.
AB  - BACKGROUND/AIMS: Although it is widely acknowledged that atherosclerosis is
      mainly a chronic inflammatory process, in which both miR-29b and interleukin-6
      (IL-6) play multifaceted roles, the association between miR-29b and IL-6 remains
      unknown. The aim of the present study was to explore the relationship between miR
      29b and IL-6 and to test whether circulating levels of miR-29b and IL-6 could
      predict atherosclerosis. METHODS: A total of 170 participants were divided into
      two groups according to carotid intima-media thickness (CIMT): study group (CIMT
      >= 0.9mm) and control group (CIMT < 0.9mm). Levels of circulating miR-29b and IL
      6 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and
      enzyme-linked immunosorbent assay (ELISA), respectively. The association of miR
      29b and IL-6 levels with CIMT was assessed using Spearman correlation analysis
      and multiple linear regression analysis. RESULTS: The study group showed higher
      miR-29b levels (31.61 +/- 3.05 vs. 27.91 +/- 1.71 Ct, p < 0.001) and IL-6 levels
      (3.40 +/- 0.67 vs. 2.99 +/- 0.37 pg/ml, p < 0.001), compared with the control
      group. CIMT was positively correlated with miR-29b (r = 0.587, p < 0.001) and IL
      6 (r = 0.410, p < 0.001), and miR-29b levels were also correlated with IL-6 (r =
      0.242, p = 0.001). Multiple linear regression analysis also showed that CIMT was
      positively correlated with miR-29b and IL-6. After adjustment for age, body mass
      index, systolic blood pressure, total cholesterol and C-reactive protein, CIMT
      was still closely correlated with miR-29b and IL-6. The combination of miR-29b
      and IL-6 (AUC = 0.901, p < 0.001) offered a better predictive index for
      atherosclerosis than either miR-29b (AUC = 0.867, p < 0.001) or IL-6 (AUC =
      0.747, p < 0.001) alone. CONCLUSION: Circulating levels of miR-29b and IL-6 may
      be independently correlated with subclinical atherosclerosis, and may serve as
      novel biomarkers for the identification of atherosclerosis.

PMID- 29197871
TI  - Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a
      Randomized Controlled Trial.
AB  - BACKGROUND/AIMS: Cardiac biomarkers are associated with cardiac abnormalities and
      adverse outcomes in dialysis patients. Our aim was to report the effect of the
      beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients.
      METHODS: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility
      Study was a randomized controlled trial comparing carvedilol to placebo. Serum
      and plasma were collected before the run-in, then 6 and 12 months post
      randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT
      ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and
      galectin-3. Left ventricular global longitudinal strain (GLS) was measured by
      echocardiography at baseline. RESULTS: Seventy-two participants were recruited of
      whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo
      (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS
      of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS
      (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median
      change scores from baseline to 12 months did not differ significantly between
      participants with complete biomarker data randomized to carvedilol (n=15) or
      placebo (n=16) for any biomarkers. CONCLUSIONS: NT-proBNP and hs-TnT were
      associated with GLS. However, changes in levels of the biomarkers from baseline
      to 12 months were not different between groups randomized to carvedilol and
      placebo.

PMID- 29197873
TI  - Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of
      CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro.
AB  - BACKGROUND/AIMS: Platelets affect endothelial progenitor cell (EPC)
      functionality, inducing their differentiation into mature endothelial cells.
      However, it remains to be established whether EPCs can influence platelet
      functionality. METHODS: Mononuclear proangiogenic cells (MPCs) and early
      outgrowth cells (EOCs) were prepared from peripheral blood mononuclear cells,
      whereas late-outgrowth endothelial cells (OECs) were prepared from cord blood
      CD34+ cells. The effect of the above cells and their supernatants on washed
      platelet aggregation was studied. The effect of OECs and their supernatant on the
      adenosine diphosphate (ADP)-induced magnitude of platelet integrin receptor
      alphaIIbbeta3 activation and on P-selectin membrane expression was investigated.
      The levels of nitric oxide (NO) and prostacyclin (PGI2) that were secreted from
      EOCs, OECs, and human umbilical vein endothelial cells (HUVECs) were also
      assessed. RESULTS: Among all progenitors, OECs and their supernatant exhibited
      the most potent inhibitory activity towards platelet aggregation. Furthermore,
      OECs and their supernatant, but not CD34+ cells, reduced alphaIIbbeta3 activation
      and P-selectin membrane expression. Finally, OECs secreted higher NO and PGI2
      levels than EOCs did. CONCLUSION: The anti-platelet effect of EPCs depends highly
      on the degree of their endothelial phenotype, with OECs expressing the highest
      potency. Therefore, the induction of OEC generation and the enhancement of their
      functionality in vivo could be a new approach for the treatment of patients at a
      high thrombotic risk.

PMID- 29197874
TI  - Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through
      ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension.
AB  - BACKGROUND/AIMS: Central blood pressure (BP) has been suggested to be a better
      estimator of hypertension-associated risks. We aimed to evaluate the association
      of 24-hour central BP, in comparison with 24-hour peripheral BP, with the
      presence of renal organ damage in hypertensive patients. METHODS: Brachial and
      central (calculated by an oscillometric system through brachial pulse wave
      analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse
      wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ
      damage was evaluated by means of the albumin to creatinine ratio and the
      estimated glomerular filtration rate. RESULTS: Fifty-four patients (25.9%) were
      affected by renal organ damage, displaying either microalbuminuria (urinary
      albumin excretion >=30 mg/g creatinine) or an estimated glomerular filtration
      rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities,
      hypertensive patients with kidney damage had higher values of office brachial
      systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime
      central and brachial SBP and PP. They also had a blunted nocturnal decrease in
      both central and brachial BP, and higher values of aortic PWV. After adjustment
      for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates
      (both central and brachial) showed significant associations with the presence of
      renal damage. Odds ratios for central BP estimates were not significantly higher
      than those obtained for brachial BP. CONCLUSION: Compared with peripheral ABPM,
      cuff-based oscillometric central ABPM does not show a closer association with
      presence of renal organ damage in hypertensive patients. More studies, however,
      need to be done to better identify the role of central BP in clinical practice.

PMID- 29197875
TI  - Efficacy and Tolerability of Leuprorelin Acetate (Eligard(r)) in Daily Practice
      in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or
      6-Month Depot Formulations in Patients with Advanced Prostate Cancer.
AB  - INTRODUCTION: We evaluated the efficacy and tolerability of 3- and 6-month
      leuprorelin acetate (LA) depot formulations (Eligard(r), Astellas Pharma GmbH) in
      patients with advanced prostate cancer treated in routine clinical practice in
      Germany. MATERIALS AND METHODS: Data was pooled from 2 prospective, open-label,
      non-interventional studies in which 1,906 patients were treated for 12 months
      with either the 3-month (n = 633) or 6-month (n = 1,273) LA formulation. RESULTS:
      Median prostate-specific antigen levels in the pooled patient population declined
      from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific
      antigen reduction was achieved in treatment-naive and pre-treated patients.
      Adverse events were documented in 8.8% of patients. CONCLUSIONS: These pooled
      data from routine clinical practice in Germany indicate that LA 3- and 6-month
      depot injections can effectively reduce prostate-specific antigen levels in a
      broad patient population with advanced prostate cancer.

PMID- 29197876
TI  - MiR-106b-5p Promotes Proliferation and Inhibits Apoptosis by Regulating BTG3 in
      Non-Small Cell Lung Cancer.
AB  - BACKGROUND/AIMS: MicroRNAs have been validated to play a crucial role in
      tumorigenesis of non-small cell lung cancer (NSCLC). Although miR-106b-5p has
      been reported to play a vital role in various malignancies the physiological
      function of miR-106b-5p in NSCLC still remain unknown. In this study, we
      investigated the role of miR-106b-5p in NSCLC. METHODS: Quantitative real-time
      polymerase chain reaction was conducted to estimate the expression of miR-106b-5p
      and BTG3 in both NSCLC tissues and cell lines. The effects of miR-106b-5p on
      proliferation were determined in vitro using CCK-8 proliferation assays, 5
      ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assays and cell
      cycle assays and the in vivo effects were evaluated by a mouse tumorigenicity
      model. Cell apoptosis and cell cycle was investigated by flow cytometric analysis
      in vitro. The molecular mechanism underlying the relevance between miR-106b-5p
      and BTG3 was confirmed by luciferase assay and western blot. RESULTS: In current
      study, we found a relatively higher miR-106b-5p and lower BTG3 expression in
      NSCLC specimens and cell lines. BTG3 was verified as a direct target of miR-106b
      5p by luciferase assay. In vitro, over-expression of miR-106b-5p promoted
      proliferation and inhibited apoptosis by down-regulating BTG3 expression. In
      vivo, miR-106b-5p promoted xenograft tumor formation. CONCLUSION: Our findings
      revealed for the first time that miR-106b-5p plays a tumorigenesis role in NSCLC
      progression by down-regulating BTG3 expression, which may lead to a novel insight
      to the potential biomarker and novel therapeutic strategies for NSCLC patients.

PMID- 29197877
TI  - Functional Characterization of a Novel Truncating Mutation in Lamin A/C Gene in a
      Family with a Severe Cardiomyopathy with Conduction Defects.
AB  - BACKGROUND/AIMS: Truncating LMNA gene mutations occur in many inherited
      cardiomyopathy cases, but the molecular mechanisms involved in the disease they
      cause have not yet been systematically investigated. Here, we studied a novel
      frameshift LMNA variant (p.D243Gfs*4) identified in three members of an Italian
      family co-segregating with a severe form of cardiomyopathy with conduction
      defects. METHODS: HEK293 cells and HL-1 cardiomyocytes were transiently
      transfected with either Lamin A or D243Gfs*4 tagged with GFP (or mCherry).
      D243Gfs*4 expression, cellular localization and its effects on diverse cellular
      mechanisms were evaluated with western blotting, laser-scanning confocal
      microscopy and video-imaging analysis in single cells. RESULTS: When expressed in
      HEK293 cells, GFP- (or mCherry)-tagged LMNA D243Gfs*4 colocalized with calnexin
      within the ER. ER mislocalization of LMNA D243Gfs*4 did not significantly induce
      ER stress response, abnormal Ca2+ handling and apoptosis when compared with
      HEK293 cells expressing another truncated mutant of LMNA (R321X) which similarly
      accumulates within the ER. Of note, HEK293-LMNA D243Gfs*4 cells showed a
      significant reduction of connexin 43 (CX43) expression level, which was
      completely rescued by activation of the WNT/beta-catenin signaling pathway. When
      expressed in HL-1 cardiomyocytes, D243Gfs*4 significantly impaired the
      spontaneous Ca2+ oscillations recorded in these cells as result of propagation of
      the depolarizing waves through the gap junctions between non-transfected cells
      surrounding a cell harboring the mutation. Furthermore, mCh-D243Gfs*4 HL-1
      cardiomyocytes showed reduced CX43-dependent Lucifer Yellow (LY) loading and
      propagation. Of note, activation of beta-catenin rescued both LY loading and LMNA
      D243Gfs*4 -HL-1 cells spontaneous activity propagation. CONCLUSION: Overall, the
      present results clearly indicate the involvement of the aberrant CX43
      expression/activity as a pathogenic mechanism for the conduction defects
      associated to this LMNA truncating alteration.

PMID- 29197878
TI  - A Rare Case of Embryonal Carcinoma in a Patient with Turner Syndrome without Y
      Chromosomal Material but Mutations in KIT, AKT1, and ZNF358 Demonstrated Using
      Exome Sequencing.
AB  - Gonadoblastoma and malignant transformations thereof can occur in females with
      Turner syndrome (TS) and Y chromosomal material. However, in females with TS and
      no Y chromosomal material, this is rarely seen. We report a female with an
      apparent 45,X karyotype (in blood and tumor) who was diagnosed with a metastatic
      embryonal carcinoma. Exome sequencing of blood and the tumor was done, and no Y
      chromosomal material was detected, while predicted deleterious mutations in KIT
      (likely driver), AKT1, and ZNF358 were identified in the tumor. The patient was
      treated with chemotherapy (first-line: cisplatin, etoposide, and bleomycin;
      second-line: paclitaxel and gemcitabine), and after that surgical debulking was
      performed. She is currently well and without signs of relapse. We conclude that
      embryonal carcinoma can apparently occur in 45,X TS without signs of Y
      chromosomal material.

PMID- 29197879
TI  - Corticosteroid-induced leukocytosis in pregnancy: A prospective observational
      study.
AB  - BACKGROUND: In the course of managing preterm labour, increasing trends of total
      white cell count raises concern for the obstetrician, suggesting a possible
      underlying infectious aetiology. Although mild leukocytosis is expected in
      pregnancy, the patterns of increment after corticosteroid administration are not
      well described beyond animal models and in a small number of human studies.
      METHODS: Seventy-three consecutive patients who required antenatal
      corticosteroids for either preterm labour or prelabour caesarean section were
      recruited and given a standard course of 12mg dexamethasone phosphate, twelve
      hours apart. Venous blood samples were taken before administration, at six hours
      and 36 hours after the first dose of dexamethasone. RESULTS: The total white
      count trend was 10.31+/-2.62 at baseline, 11.44+/-3.05 at six hours and 12.20+/
      3.49 at 36 hours. Neutrophil-lymphocyte ratio was 3.60+/-1.31, 8.73+/-3.63 and
      3.24+/-1.49 respectively, reflecting relative neutrophilia and lymphopenia which
      normalised by 36 hours. CONCLUSION: In contrast to previous studies, we found
      only a slight increment in total white cell count of about 10%. The marginal
      changes described in our study would not normally raise any clinical concern,
      although vigilance should be exercised if higher levels were observed.

PMID- 29197880
TI  - Construct validity and internal consistency reliability of the Malay version of
      the 21-item depression anxiety stress scale (Malay-DASS-21) among male outpatient
      clinic attendees in Johor.
AB  - BACKGROUND: The 21-item English version of the Depression Anxiety Stress Scale
      (DASS-21) has been proposed as a method for assessing self-perceived depression,
      anxiety and stress over the past week in various clinical and nonclinical
      populations. Several Malay versions of the DASS-21 have been validated in various
      populations with varying success. One particular Malay version has been validated
      in various occupational groups (such as nurses and automotive workers) but not
      among male clinic outpatient attendees in Malaysia. OBJECTIVE: To validate the
      Malay version of the DASS-21 (Malay-DASS-21) among male outpatient clinic
      attendees in Johor. METHODS: A validation study with a random sample of 402 male
      respondents attending the outpatient clinic of a major public outpatient clinic
      in Johor Bahru and Segamat was carried out from January to March 2016. Construct
      validity of the Malay-DASS-21 was examined using Exploratory Factor Analysis (KMO
      = 0.947; Bartlett's test of sphericity is significant, p<0.001) through Principal
      Component Analysis and orthogonal (varimax) rotation with Kaiser Normalization to
      confirm the psychometric properties of the Malay-DASS- 21 and the internal
      consistency reliability using Cronbach's alpha. RESULTS: Construct validity of
      the Malay-DASS-21 based on eigenvalues and factor loadings to confirm the three
      factor structure (depression, anxiety, and stress) was acceptable. The internal
      consistency reliability of the factor construct was very impressive with
      Cronbach's alpha values in the range of 0.837 to 0.863. CONCLUSIONS: The present
      study showed that the Malay- DASS-21 has acceptable psychometric construct and
      high internal consistency reliability to measure self-perceived depression,
      anxiety and stress over the past week in male outpatient clinic attendees in
      Johor. Further studies are necessary to revalidate the Malay-DASS-21 across
      different populations and cultures, and using confirmatory factor analyses.

PMID- 29197881
TI  - What are the direct medical costs of managing Type 2 Diabetes Mellitus in
      Malaysia?
AB  - INTRODUCTION: An economic analysis was performed to estimate the annual cost of
      diabetes mellitus to Malaysia. METHODS: We combined published data and clinical
      pathways to estimate cost of follow-up and complications, then calculated the
      overall national cost. Costs consisted of diabetes follow-up and complications
      costs. RESULTS: Patient follow-up was estimated at RM459 per year. Complications
      cost were RM42,362 per patient per year for nephropathy, RM4,817 for myocardial
      infarction, RM5,345 for stroke, RM3,880 for heart failure, RM5,519 for foot
      amputation, RM479 for retinopathy and RM4,812 for cataract extraction.
      CONCLUSION: Overall, we estimated the total cost of diabetes as RM2.04 billion
      per year for year 2011 (both public and private sector). Of this, RM1.40 billion
      per year was incurred by the government. Despite some limitations, we believe our
      study provides insight to the actual cost of diabetes to the country. The high
      cost to the nation highlights the importance of primary and secondary prevention.

PMID- 29197882
TI  - Islamic medical jurisprudence syllabus: A Review in Saudi Arabia.
AB  - INTRODUCTION: The ever-increasing technological advances of Western medicine have
      created new ethical issues awaiting answers and response. The use of genetic
      therapy, organ transplant, milk-banking, end-of-life care and euthanasia are of
      paramount importance to the medical students and need to be addressed. METHODS: A
      series of searches were conducted of Medline databases published in English
      between January 2000 and January 2017 with the following keywords: medical
      ethics, syllabus, Islam, jurisprudence. RESULTS: Islamic medical jurisprudence is
      gaining more attention in some medical schools. However, there is still lack of
      an organised syllabus in many medical colleges. CONCLUSION: The outlines of a
      syllabus in Islamic medical jurisprudence including Islamic values and moral
      principles related to both the practice and research of medicine are explored.

PMID- 29197883
TI  - Clinical characteristics, treatment and 2-year outcomes in Malaysian and Bruneian
      patients with stable coronary artery within the worldwide CLARIFY registry.
AB  - INTRODUCTION: The on-going, international, prospective, observational,
      longitudinal CLARIFY registry is investigating the demographics, clinical
      profiles, management and outcomes of patients with stable coronary artery disease
      (CAD). This paper assesses baseline characteristics, treatment, and clinical
      outcomes at two years' follow-up of Malaysian/Bruneian patients compared with the
      overall registry population. METHOD: Between November 2009 and July 2010,
      outpatients from 45 countries who met the criteria for stable CAD were recruited
      into the registry. Baseline characteristics were documented at enrolment, and
      patients were reassessed during their annual visits over a five-year follow-up
      period. Key outcomes measured were sudden death and cardiovascular (CV) death,
      non-CV death and CV morbidity. RESULTS: At baseline, 33,283 patients were
      available for analysis within the registry; 380 and 27 were Malaysians and
      Bruneians, respectively. The mean ages of Malaysian/Bruneian patients and the
      rest of the world (RoW) were 57.83 +/-9.98 years and 64.23 +/- 10.46 years,
      respectively (p<0.001). The median body mass index values were 26.6 (24.4-29.6)
      kg/m2 and 27.3 (24.8-30.3) kg/m2, respectively (p=0.014). Malaysian/Bruneian
      patients had lower rates of myocardial infarction (54.55% versus 59.76%, p=0.033)
      and higher rates of diabetes (43.24% versus 28.99%, p<0.001) and dyslipidaemia
      (90.42% versus 74.66%, p<0.001) compared with the RoW. Measured clinical outcomes
      in Malaysian and Bruneian patients at 2-years follow-up were low and generally
      comparable to the RoW. CONCLUSION: Malaysian/Bruneian patients with stable CAD
      tend to be younger with poorer diabetic control compared with the RoW. However,
      they had similar outcomes as the main registry following two years of treatment.

PMID- 29197884
TI  - Comparison between FEV1/FEV6 and FEV1/FVC as screening of chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To compare FEV1/FEV6 to the standard spirometry (FEV1/FVC) as a
      screening tool for COPD. METHODS: This cross-sectional study was conducted at
      Hospital Tuanku Fauziah, Perlis, Malaysia from August 2015 to April 2016.
      FEV1/FEV6 and FEV1/FVC results of 117 subjects were analysed. Demographic data
      and spirometric variables were tabulated. A scatter plot graph with Spearman's
      correlation was constructed for the correlation between FEV1/FEV6 and FEV1/FVC.
      The sensitivity, specificity, positive and negative predictive values of
      FEV1/FEV6 were determined with reference to the gold standard of FEV1/FVC ratio
      <0.70. Receiver-operator characteristic (ROC) curve analysis and Kappa statistics
      were used to determine the FEV1/FEV6 ratio in predicting an FEV1/FVC ratio <0.70.
      RESULTS: Spearman's correlation with r = 0.636 (P<0.001) was demonstrated. The
      area under the ROC curve was 0.862 (95% confidence interval [CI]: 0.779 - 0.944,
      P<0.001). The FEV1/FEV6 cut-off with the greatest sum of sensitivity and
      specificity was 0.75. FEV1/FEV6 sensitivity, specificity, positive and negative
      predictive values were 93.02%, 67.74%, 88.89% and 77.78% respectively. There was
      substantial agreement between the two diagnostic cut-offs (kappa = 0.634; 95% CI:
      0.471 - 0.797, P<0.001) CONCLUSIONS: The FEV1/FEV6 ratio can be considered to be
      a good alternative to the FEV1/FVC ratio for screening of COPD. Larger
      multicentre study and better education on spirometric techniques can validate
      similar study outcome and establish reference values appropriate to the
      population being studied.

PMID- 29197885
TI  - The predicting roles of reasons for living and social support on depression,
      anxiety and stress among young people in Malaysia.
AB  - INTRODUCTION: This research examined the predicting roles of reasons for living
      and social support on depression, anxiety and stress in Malaysia. METHOD: This
      research was carried out on a sample of 263 participants (age range 12-24 years
      old), from Klang Valley, Selangor. The survey package comprises demographic
      information, a measure of reasons for living, social support, depression, anxiety
      and stress. To analyse the data, correlation analysis and a series of linear
      multiple regression analysis were carried out. RESULTS: Findings showed that
      there were low negative relationships between all subdomains and the total score
      of reasons for living and depression. There were also low negative relationships
      between domain-specific of social support (family and friends) and total social
      support and depression. In terms of the family alliance, self-acceptance and
      total score of reasons for living, they were negatively associated with anxiety,
      whereas family social support was negatively associated with stress. The linear
      regression analysis showed that only future optimism and family social support
      found to be the significant predictors for depression. Family alliance and total
      reasons for living were significant in predicting anxiety, whereas family social
      support was significant in predicting stress. CONCLUSION: These findings have the
      potential to promote awareness related to depression, anxiety, and stress among
      youth in Malaysia.

PMID- 29197886
TI  - Bullying and truancy: Predictors to sexual practices among school-going
      adolescents in Malaysia - a cross-sectional study.
AB  - INTRODUCTION: Adolescents' involvement in sexual practices are becoming a major
      public health concern in Malaysia. This study aims to determine the prevalence of
      sexual practices among Malaysian school-going adolescents and its predictive
      factors. METHODS: A cross-sectional study was carried out from April 2012 till
      September 2012 among 16-year-old school adolescents from two different schools.
      They were selected through simple random sampling and these adolescents answered
      a self-administered questionnaire consisting of three sections i.e. socio
      demography, risk-taking behaviours and family-adolescents relationship. Data were
      analysed using Pearson Chi-Square test while Simple Logistic Regression and
      Multiple Logistic Regression were applied to determine the predictive factors.
      RESULTS: The prevalence of sexual practices among the adolescents was 30.1% in
      which they were either involved in pornography (26.8%), pre-sexual activities
      (8.5%) or premarital sex (2.9%). Six predictive factors associated with sexual
      practices among this age group were identified which were male (adjusted Odds
      Ratio (aOR) 2.7, 95% Confidence Interval (95%CI) 1.4 to 2.5), truancy (aOR 2.3,
      95%CI 1.3 to 4.2), bully (aOR 3.5, 95%CI 1.7 to 7.3), hanging out (aOR 2.8, 95%
      1.4 to 5.6), staying out late (aOR 3.2, 95%CI 1.5 to 6.8) and conflict with
      family (aOR 4.1, 95%CI 1.9 to 8.9). DISCUSSION: Asian background differs from the
      western countries and findings of this study may suggest suitable intervention
      programmes that can prevent high-risk sexual practices among Asian school-going
      adolescents.

PMID- 29197887
TI  - Important differential in a patient presenting with neuropsychiatric symptoms:
      Anti-N-Methyl-D-Aspartate receptor encephalitis.
AB  - Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an immune mediated
      condition, which remains relatively unknown in Malaysia outside tertiary
      hospitals with neurology unit. It is often misdiagnosed as a psychiatric illness
      before definitive treatment is instituted. We report here an 18-year-old man who
      initially presented to the psychiatry unit before he was subsequently diagnosed
      as having anti-NMDAR encephalitis. To our knowledge, this is the first reported
      case of anti-NMDAR encephalitis in the east coast of Peninsular Malaysia.

PMID- 29197888
TI  - Congenital arhinia - First published case in Malaysia.
AB  - Congenital arhinia is one of the rare craniofacial malformation that may cause
      severe respiratory distress at birth due to upper airway obstruction. Our
      patient, whose abnormalities were only detected after delivery in our centre, is
      the first reported case of congenital arhinia in Malaysia. Contrary to popular
      belief that neonates are obligate nasal breather, our patient adapted well to
      breathing through mouth before an elective tracheostomy was performed on day four
      of life.

PMID- 29197889
TI  - Acute necrotising encephalopathy of childhood: A review of two cases.
AB  - Acute necrotising encephalopathy of childhood (ANEC) is an uncommon disease with
      characteristic clinical and imaging findings. We present two cases of ANEC
      secondary to Respiratory Syncytial Virus (RSV) and mycoplasma infections. An
      eight-month-old boy presented with features of gastroenteritis but soon developed
      multiple episodes of seizures. Blood and CSF cultures were negative but
      nasopharyngeal aspirate immunofluorescence was positive for RSV. A nine-year-old
      girl presented with abnormal behaviour following two days of prodromal symptoms.
      Her serological markers implicated mycoplasma (IgM titre 1: 640). CT brain of
      both patients showed bilateral symmetrical thalamic hypodensities, while MRI
      revealed more extensive white matter involvements.

PMID- 29197890
TI  - Siphoning diesel: a fatal mistake.
AB  - Diesel is commonly used as fuel for engines and is distilled from petroleum.
      Diesel has toxic potential and can affect multiple organs. Exposure can occur
      after ingestion, inhalation or through the dermal route. The practice of
      siphoning diesel using a rubber tubing and the mouth is common in rural
      communities. This can lead to accidental ingestion and aspiration. Here we report
      a case of a patient who accidentally ingested diesel during siphoning, which
      caused extensive erosion of the oral cavity and oesophagus leading to
      pneumomediastinum and severe chemical lung injury. The patient responded well
      initially to steroids and supportive care but required prolonged hospitalisation.
      He developed complications of nosocomial infection and succumbed 23 days after
      admission.

PMID- 29197891
TI  - Management of malodour fungating wound with nanocrystalline silver coated
      dressing.
AB  - Chronic exudative malodorous fungating wound of four years at the right arm due
      to diffuse large B cell lymphoma managed with silver dressings. In two months of
      application with nanocrystalline silver coated dressings, there was significant
      improvement in wound.

PMID- 29197892
TI  - Relapse of B-cell acute lymphoblastic leukaemia presenting as right aural polyp
      with facial and mandibular nerves palsy.
AB  - A patient presenting with an ear polyp is a common finding in otorhinolaryngology
      practice. The common causes include chronic otitis media and cholesteatoma. We
      report an adult female patient with a history of acute leukaemia presenting with
      chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed
      as relapse of B-cell acute lymphoblastic leukaemia based on histopathological
      examination. The presentation may be similar to an inflammatory pathology of the
      middle ear, making it misleading.

PMID- 29197893
TI  - Management of concurrent thoracic and abdominal aortic aneurysms.
AB  - Concurrent thoracic and abdominal aortic aneurysm is uncommon. It remains a
      formidable surgical challenge to vascular surgeons, as decision to treat in
      staged or simultaneous setting still debatable. We present, here, a case of a 62
      year-old-man with asymptomatic concurrent thoracic and abdominal aortic
      aneurysms, which was successfully treated with two-stage hybrid endovascular
      repair. The aim of this case report is to discuss the treatment options
      available, possible associated complications and measures to prevent them.

PMID- 29197894
TI  - Diagnostic challenge of Burkitt's lymphoma at early age.
AB  - A four-year-old Ibanese boy presented with subacute abdominal distension for two
      months duration. Ultrasound and computed tomography (CT) scan showed solid liver
      masses as well as bowel and intraperitoneal lesions. Initial diagnosis of
      intraperitoneal inflammatory process as in tuberculosis with non-liquefied liver
      abscess with differential diagnosis of neoplastic process was made. Liver biopsy
      and peritoneal fluid analysis revealed Burkitt's lymphoma (BL). We aim to
      highlight the diagnostic challenge of BL in this young age group emphasizing on
      the ultrasound and CT features of intraabdominal BL. We would also want to stress
      the importance of early diagnosis of BL as it is known to be the most aggressive
      tumour within 24 hours yet to have good survival if early diagnosis was made.

PMID- 29197895
TI  - Identification of Key Genes in Colorectal Cancer Regulated by miR-34a.
AB  - BACKGROUND The aim of this study was to screen the molecular targets of miR-34a
      in colorectal cancer (CRC) and construct the regulatory network, to gain more
      insights to the pathogenesis of CRC. MATERIAL AND METHODS The microarray data of
      CRC samples and normal samples (GSE4988), as well as CRC samples transformed with
      miR-34a and non-transfected CRC samples (GSE7754), were downloaded from the Gene
      Expression Omnibus (GEO) database. The differently expressed genes (DEGs) were
      identified via the LIMMA package in R language. The Database for Annotation,
      Visualization and Integrated Discovery (DAVID) was used to identify significant
      Gene Ontology (GO) terms and pathways in DEGs. The targets of miR-34a were
      obtained via the miRWalk database, and then the overlaps between them were
      selected out to construct the regulatory network of miR-34a in CRC using the
      Cytoscape software. RESULTS A total of 392 DEGs were identified in CRC samples
      compared with normal samples, including 239 upregulated genes and 153
      downregulated ones. These DEGs were enriched in 75 GO terms and one Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway. At the same time, 332 DEGs (188
      upregulated and 144 downregulated) were screened out between miR-34a transformed
      CRC and miR-34a non-transfected CRC samples and they were enriched in 20 GO terms
      and eight KEGG pathways. Six overlapped genes were identified in two DEGs groups.
      There were 1,668 targets of miR-34a obtained via the miRWalk database, among
      which 21 were identified differently expressed in miR-34a transformed CRC samples
      compared with miR-34a non-transfected CRC samples. Two regulatory networks of miR
      34a in CRC within these two groups of overlapped genes were constructed
      respectively. CONCLUSIONS Pathways related to cell cycle, DNA replication, oocyte
      meiosis, and pyrimidine metabolism might play critical roles in the progression
      of CRC. Several genes such as SERPINE1, KLF4, SEMA4B, PPARG, CDC45, and KIAA0101
      might be the targets of miR-34a and the potential therapeutic targets of CRC.

PMID- 29197896
TI  - miRNA-1273g-3p Involvement in Development of Diabetic Retinopathy by Modulating
      the Autophagy-Lysosome Pathway.
AB  - BACKGROUND Diabetic retinopathy (DR) is one of the most common and serious
      complications of diabetes mellitus (DM). The autophagy-lysosome pathway (ALP) is
      one of the main intracellular self-digestive degradation systems. Lysosomal
      impairment and autophagic dysfunction are early events in the pathogenesis of DR,
      suggesting autophagy might be a novel therapeutic strategy for DR treatment.
      MATERIAL AND METHODS In our study, we screened a differentially expressed miRNA,
      miR-1273g-3p, in streptozotocin (STZ)-injected DR rat retinal pigment epithelial
      (RPE) cells. miR-1273g-3p inhibitor and mimic were employed to treat RPE cells to
      assess the role of miR-1273g-3p. QRT-PCR and Western blot analysis were performed
      to examine the function of miR-1273g-3p on ALP-related and DR-related proteins.
      RESULTS miR-1273g-3p was highly expressed in STZ-induced DM RPE cells. miR-1273g
      3p mimic promoted the expression of DR-related MMP-2, MMP-9, and TNF-alpha
      proteins, and ALP-related LC3, cathepsin B, and cathepsin L factors, but miR
      1273g-3p inhibitor suppressed the levels of these factors. CONCLUSIONS miR-1273g
      3p is involved in the progression of DR by modulating the autophagy-lysosome
      pathway. These findings provided new evidence of the close relationship between
      DR and ALP, and reveal a new target for DR therapy.

PMID- 29197897
TI  - New Zealand asthma guidelines updated.

PMID- 29197898
TI  - Asthma and Respiratory Foundation NZ child and adolescent asthma guidelines: a
      quick reference guide.
AB  - The purpose of the New Zealand Child and adolescent asthma guidelines: a quick
      reference guide is to provide simple, practical, evidence-based recommendations
      for the diagnosis, assessment and management of asthma in children and
      adolescents in New Zealand, with the aim of improving outcomes and reducing
      inequities. The intended users are health professionals responsible for
      delivering asthma care in the community and hospital emergency department
      settings, and those responsible for the training of such health professionals.

PMID- 29197899
TI  - Breastfeeding indicators among a nationally representative multi-ethnic sample of
      New Zealand children.
AB  - AIMS: To describe breastfeeding initiation and duration, and demographic
      associations with breastfeeding duration within a representative sample of New
      Zealand infants. METHODS: In 6,685 singletons enrolled in the Growing Up in New
      Zealand cohort we described breastfeeding initiation (96%), any (94%) and
      exclusive (93%) breastfeeding (EBF) duration. We used adjusted relative risk (RR)
      and 95% confidence intervals (CI) to describe associations with breastfeeding
      duration. RESULTS: Breastfeeding initiation occurred for 97%. Sixteen percent
      were EBF to age six months and 13% were breastfed to age 24 months. Exclusive
      breastfeeding for >=4 months was less likely for children of mothers of Maori
      (RR=0.80, 95% CI 0.73-0.87), Pacific (0.90, 95% CI 0.83-0.98) or Asian (0.80, 95%
      CI 0.74-0.86) ethnicity. Children of mothers aged 20-29 years (1.24, 95% CI 1.04
      1.49); >=30 years (1.36, 95% CI 1.14-1); with a tertiary education (1.14, 95% CI
      1.08-1.21); or planned pregnancy (1.14, 95% CI 1.08-1.21); and children with
      older siblings (RR=1.31, 95% CI 1.17-1.47) were more likely to be exclusively
      breastfed for >=4 months. Children were more likely to be breastfed >=6 months if
      their mother was aged 20-29 (1.26, 95% CI 1.10-1.45) or >=30 years (1.40, 95% CI
      1.22-1.61), had a tertiary education (1.11, 95% CI 1.06-1.59) or planned
      pregnancy (1.11, 95% CI 1.06-1.15), or if they had older siblings (1.04, 95% CI
      1.00-1.08). CONCLUSION: In New Zealand, most children are initially breastfed,
      however a large proportion did not receive the recommended duration of any or
      exclusive breastfeeding. Maternal age, education, parity and pregnancy planning
      identify children at risk of shorter duration of breastfeeding and EBF, and
      maternal ethnicity identifies children at risk of shorter EBF duration.

PMID- 29197900
TI  - Teaching quality improvement to medical students: over a decade of experience.
AB  - AIM: To describe how we incorporate experiential quality improvement (QI)
      learning at the University of Auckland by integrating a clinical audit project
      into the Year 6 obstetrics and gynaecology clinical attachment. METHODS: Students
      gain insight into the relevance of QI while engaged in day-to-day clinical work.
      Students work with a clinical supervisor to identify an area for potential
      improvement, set a standard of care, measure current practice, investigate
      reasons for deviation from the standard and make real-world suggestions to close
      the gap between best evidence and observed practice. RESULTS: Since 2004, over
      1,250 projects have been completed, and two journal articles published. Many of
      the student projects result in actual improvements to clinical processes of care,
      and lead to strengthening of academic and service provider learning networks and
      partnerships. CONCLUSIONS: Performing a hands-on project within the constraints
      and context of a busy women's health service is a feasible and effective method
      of teaching QI. Medical schools have an integral role to play in ensuring future
      healthcare professionals are equipped with QI knowledge, skills and attitudes.
      Experiential QI learning enhances clinical teaching and training, and is
      important in preparing future clinicians to incorporate QI into their daily
      practice.

PMID- 29197901
TI  - Deaf New Zealand Sign Language users' access to healthcare.
AB  - AIMS: The research described was undertaken as part of a Sub-Regional Disability
      Strategy 2017-2022 across the Wairarapa, Hutt Valley and Capital and Coast
      District Health Boards (DHBs). The aim was to investigate deaf New Zealand Sign
      Language (NZSL) users' quality of access to health services. Findings have formed
      the basis for developing a 'NZSL plan' for DHBs in the Wellington sub-region.
      METHODS: Qualitative data was collected from 56 deaf participants and family
      members about their experiences of healthcare services via focus group,
      individual interviews and online survey, which were thematically analysed.
      Contextual perspective was gained from 57 healthcare professionals at five
      meetings. Two professionals were interviewed, and 65 staff responded to an online
      survey. A deaf steering group co-designed the framework and methods, and
      validated findings. RESULTS: Key issues reported across the health system
      include: inconsistent interpreter provision; lack of informed consent for
      treatment via communication in NZSL; limited access to general health information
      in NZSL and the reduced ability of deaf patients to understand and comply with
      treatment options. This problematic communication with NZSL users echoes
      international evidence and other documented local evidence for patients with
      limited English proficiency. CONCLUSION: Deaf NZSL users face multiple barriers
      to equitable healthcare, stemming from linguistic and educational factors and
      inaccessible service delivery. These need to be addressed through policy and
      training for healthcare personnel that enable effective systemic responses to
      NZSL users. Deaf participants emphasise that recognition of their identity as
      members of a language community is central to improving their healthcare
      experiences.

PMID- 29197902
TI  - A New Zealand platform to enable genetic investigation of adverse drug reactions.
AB  - A multitude of factors can affect drug response in individuals. It is now well
      established that variations in genes, especially those coding for drug
      metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic
      profile of a drug, impacting on efficacy and often resulting in drug-induced
      toxicity. The UDRUGS study is an initiative from the Carney Centre for
      Pharmacogenomics to biobank DNA and store associated clinical data from patients
      who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is
      to provide a genetic explanation of drug-induced ADRs using methods ranging from
      Sanger sequencing to whole exome and whole genome sequencing. Participants for
      the UDRUGS study are recruited from various sources, mainly via referral through
      clinicians working in Canterbury District Health Board, but also from district
      health boards across New Zealand. Participants have also self-referred to us from
      word-of-mouth communication between participants. We have recruited various ADRs
      across most drug classes. Where possible, we have conducted genetic analyses in
      single or a cohort of cases to identify known and novel genetic association(s) to
      offer an explanation to why the ADR occurred. Any genetic results relevant to the
      ADR are communicated back to the referring clinician and/or participant. In
      conclusion, we have developed a programme for studying the genetic basis of
      severe, rare or unusual ADR cases resulting from pharmacological treatment.
      Genomic analyses could eventually identify most genetic variants that predispose
      to ADRs, enabling a priori detection of such variants with high throughput DNA
      tests.

PMID- 29197903
TI  - Acupuncture, ACC and the Medicines Act.
AB  - Acupuncture is covered under the Accident Compensation (Liability to Pay or
      Contribute to Cost of Treatment) Regulations 2003, and is therefore eligible for
      Accident Compensation Corporation payments for the treatment of personal
      injuries. This study searched New Zealand acupuncturists' websites for
      therapeutic claims that may breach Section 58(1)(a) of the Medicines Act. A
      search of acupuncturists' websites shows that many claim to be able to treat a
      wide range of conditions, despite a lack of evidence showing the efficacy of
      acupuncture in the treatment of those conditions. Practitioners and owners of
      websites likely to be in breach of the Medicines Act include many committee
      members from acupuncture's professional bodies.

PMID- 29197904
TI  - Exposure to respirable crystalline silica in the construction industry-do we have
      a problem?
AB  - AIMS: To assess personal exposure to respirable dust and respirable crystalline
      silica (RCS) in New Zealand construction workers. METHODS: In a pilot study, 39
      personal samples were collected from a cross-section of workers engaged in a
      range of tasks performed on construction sites that were expected to entail
      exposure to respirable crystalline silica. Nine static samples were taken at
      locations adjacent to these tasks. Particle size-selective sampling heads were
      used to collect the respirable fraction of airborne particulates. Dust
      concentrations were determined gravimetrically, while crystalline silica was
      analysed using x-ray diffraction. RESULTS: Almost half of the personal
      crystalline silica samples exceeded the New Zealand Workplace Exposure Standard
      (NZ WES), while 56% exceeded the more stringent international recommendation
      (ACGIH TLV). The tasks associated with the highest RCS levels were concrete
      grinding and cutting. Two of four static samples collected close to (silica
      containing) Linea board cutting exceeded the ACGIH TLV for RCS, indicating the
      potential for bystander exposure. CONCLUSIONS: A large proportion of workers
      performing common tasks in the construction industry may be exposed to levels of
      respirable dust and crystalline silica exceeding national standards and
      international recommendations. These results suggest that workers in this
      industry may be at risk of developing silica-related diseases, including
      silicosis, lung cancer, COPD and chronic renal disease. Action is required to
      improve dust control to reduce silica exposure and the associated health risks.

PMID- 29197905
TI  - Physician advocacy in Western medicine: a 21st century challenge.
AB  - Physician advocacy occurs when doctors speak up for the health and healthcare of
      patients and communities. Historically, this was strong in some Western countries
      with doctors finding that it enhanced their authority, prestige and power. But it
      weakened in the 20th century when the biomedical model of heath triumphed and
      medicine became a dominant profession. In the second part of the 20th century,
      this dominance was threatened by political, technological and socioeconomic
      forces. These weakened medicine's state support, brought it under managerial
      control and undermined the social contract on which trust between doctors and the
      community was based. Defence of the profession was assumed by medical colleges,
      societies and associations. They had some success in retaining professional
      autonomy but did not undertake open advocacy, particularly on social justice
      issues, and did not therefore enhance their standing in the community. Opinion is
      divided on the level of advocacy that it is ethically proper for the medical
      profession to employ. Some contend doctors should only advise authorities when
      expert opinion is requested. Others contend doctors should speak out proactively
      on all health issues, and that collective action of this type is a hallmark of
      professionalism. This lack of consensus needs to be debated. Recent developments
      such as clinical leadership have not revitalised physician advocacy. However,
      continued deterioration of the UK National Health Service has led some English
      medical colleges to take up open advocacy in its defence. It is to be seen
      whether medical colleges elsewhere follow suit, as and when their healthcare
      systems are similarly threatened.

PMID- 29197906
TI  - Asbestos-worker exposure, family disease.
AB  - Family members, mostly female, can be at risk of asbestos-related disease as a
      result of the transfer of asbestos from the workplace to the home on the hair,
      boots and clothes of the worker. It is argued that in these cases the home should
      be recognised as an extension of the workplace and that the employer has a duty
      of care to contain and control the asbestos. Given these circumstances, the
      family member with the disease should be entitled to cover under the Accidence
      Compensation Legislation.

PMID- 29197907
TI  - Fanconi anaemia and oral squamous cell carcinoma: management considerations.
AB  - Fanconi anaemia (FA) is a rare multi-system genetic disorder where patients are
      susceptible to the development of oral malignancies. Clinicians involved in their
      management should be vigilant in detecting lesions early, and an individualised
      treatment plan should then be formulated. Although surgery forms the mainstay of
      oncological treatment, adjuvant therapy can be instituted with care.
      Unfortunately, prognosis is poor, and close long-term follow-up is required. This
      short report describes pertinent management considerations in relation to a case
      of oral squamous cell carcinoma.

PMID- 29197908
TI  - Aggressive prostate cancer incidence in New Zealand-"united we fall, divided we
      stand".
AB  - Prostate cancer is an important health burden to the healthcare system of any
      country. However, with the current prostate-specific antigen biomarker having low
      predictive value even for diagnostic purposes, the challenge is still open to
      tackle this chronic disease. There have been a number of studies which have
      indicated and encouraged a multi-directional approach to combat this disease. We
      have been carrying out a multi-directional approach in order to identify certain
      New Zealand-specific factors which may be drivers for this cancer and its
      aggressive forms. These will be explained in further detail in this research
      letter.

PMID- 29197909
TI  - Could nail and joint alterations make the difference between psoriatic arthritis
      and osteoarthritis during the ultrasonographic evaluation of the distal
      interphalangeal joints?
AB  - .

PMID- 29197910
TI  - Detection and characterization of small superficially located focal liver lesions
      by contrast-enhanced ultrasound with high frequency transducers.
AB  - AIM: To evaluate the benefits of contrast-enhanced ultrasound (CEUS) with high
      frequency transducers in the detection and characterization of small
      superficially located focal liver lesions (FLLs). MATERIAL AND METHODS: From
      January 2015 to October 2016, 27 superficial FLLs detected by MRI were examined,
      first with the low frequency convex transducer (1-5 MHz) and afterwards with a
      high frequency transducer (7.5-12 MHz). High frequency dynamic CEUS was performed
      after a bolus injection of 2.4 ml SonoVue(r). FLLs were confirmed by
      histopathology after surgery (n=18) or ultrasound guided 18-gauge core-needle
      biopsy (n=8), or by MRI follow-up (n =1). RESULTS: The mean diameter of FLLs was
      10.5+/-3.1 mm, and meandepth was 6.2+/-5.3 mm. While using a high frequency
      transducerthe detection rate of FLLs (100%, 27/27) was significantly higher than
      low frequency transducer (25.9%, 7/27) (p<0.05). The overall sensitivity,
      specificity and diagnostic accuracy were significantly improved by CEUS with a
      high frequency transducer (sensitivity 88.9%; specificity 92.6%; accuracy 96.2%).
      CONCLUSION: Combining CEUS with the performance of high-frequency transducers is
      a promising technique to improve the detection and accurate diagnosis of small
      and superficial FLLs appearing indistinctive on BMUS.

PMID- 29197911
TI  - Intra- and inter-observer variation and accuracy using different shear wave
      elastography methods to assess circumscribed objects - a phantom study.
AB  - AIMS: The elastic properties of circumscribed tissues (e.g., tendons, lymph
      nodes, prostates, brain tumors) are of considerable clinical interest. The
      purpose of this study was thus to compare the Intra-/Inter-observer variation and
      accuracy in vitro of point shear wave elastography (pSWE) with that of 2D-SWE and
      to assess 2D-SWE's precision with variable ROI (vROI) incircumscribed objects.
      MATERIAL AND METHODS: Round targets (Elasticity QA Phantom Model 049) were
      examined for varying degrees of stiffness (8, 14, 45, and 80 kPa) and diameters
      (20/10 mm). Three ultrasound systems and four probes were applied (pSWE:
      Acuson/S3000 9L4/4C1 and Epiq7 C51, 2D-SWE: Aplio/500 PVT375BT). Three different
      ROIs were used, namely fixed ROI (fROI) and variable ROI: rectangular-best-fitted
      ROI, and round-best-fitted ROI. Each measurement was performed twice by four
      observers. RESULTS: A total of 3,604 measurements were conducted. The intra
      observer variation of 2D-SWE measurements indicated better agreement (Intraclass
      Correlation Coefficient (ICC) = 0.971; 95% CI=[0.945; 0.985]), than for the pSWE
      measurements (ICC = 0.872; 95% CI=[0.794; 0.92]). With both methods, the shear
      wave elastography applied showed low inter-observer variation: ICC = 0.980; 95%
      CI=[0.970; 0.987]. However, a significant difference was observed between fROI
      (pSWE) and vROI (2D-SWE) on circumscribed objects in terms of accuracy. The
      lowest degree of observationerror was detected in situations where the ROI was
      not "best fitted", but placed within the target of 3mm from the border (target
      diameter: 20mm; mean relative error = 0.15). CONCLUSIONS: When estimating the
      elastic properties of circumscribed tissues, the different measurement techniques
      performed by commercial shear wave elastography systems reveal a strong
      susceptibility for observational errors, depending upon the fixed vs. variable
      ROI of the pSWE vs. 2D-SWE technique.

PMID- 29197912
TI  - Point shear wave elastography (pSWE) using Acoustic Radiation Force Impulse
      (ARFI) imaging: a feasibility study and norm values for renal parenchymal
      stiffness in healthy children and adolescents.
AB  - AIMS: To evaluate the applicability of point shear wave elastography (pSWE) for
      measuring renal parenchymal stiffness in healthy children and adolescents and to
      establish norm values for shear wave speed (SWS) using two ARFI methods and
      ultrasound probes. MATERIAL AND METHODS: We prospectively investigated 264
      children (43.9% males). pSWE (Virtual TouchTM Quantification and Virtual TouchTM
      Imaging Quantification (VTQ and VTIQ; Siemens, Germany)) was performed in the
      renal cortex of 528 healthy kidneys using a 1-6 MHz convex and a 4-9 MHz linear
      ultrasound probe in ventrolateral and dorsal examinations. Feasibility and
      reproducibility of pSWE measurements were evaluated. SWS values were analysed
      with regard to age, body dimensions, kidney volume and measuring depth. RESULTS:
      pSWE measurements were successful in >95% of subjects using the low and in <60%
      using the high-frequency probe. Mean SWS values (m/s) differed by method and
      probe: 2.10+/-0.43 (VTQ1-6MHz, convex, ventrolateral), 2.30+/-0.37 (VTQ1-6MHz,
      convex, dorsal), 1.58+/-0.44 (VTQ4-9MHz, linear, dorsal) and 1.96+/-0.27 (VTIQ4
      9MHz, linear, dorsal). SWS was positively correlated with age, weight and body
      height, but independent of sex, BMI, or kidney volume and depth. CONCLUSIONS:
      pSWE (VTQ) is a feasible method to evaluate renal parenchymal stiffness in
      children of all ages. SWS values are age and weight dependent and differ
      significantly between high- and low-frequency probes. High-frequency probes and
      VTIQ should only be used in children <10 years.

PMID- 29197913
TI  - An "alternative finger" in robotic-assisted thoracic surgery: intraoperative
      ultrasound localization of pulmonary nodules.
AB  - AIM: Robotic-assisted thoracic surgery (RATS) has become a promising treatment
      for pulmonary neoplasms. During RATS, intraoperative ultrasonography can act as
      an "alternative finger" to "touch" and locate lesions, especially pulmonary
      nodules. This study was aimed to investigate the efficacy of intraoperative
      ultrasonographic localization during da Vinci RATS procedures. MATERIAL AND
      METHODS: Patients with pulmonary nodules were randomly divided into an
      Experimental Group and Control Group in which nodules were respectively located
      using intraoperative ultrasonography or by the surgeon's anatomic knowledge. The
      success rates and relevant localization factors were compared between the groups
      and analyzed to conclude the efficacy of intraoperative ultrasonography.
      Additionally, the intraoperative ultrasonography learning curve was analyzed to
      evaluate each surgeon's ability to independently perform intraoperative
      ultrasonography. RESULTS: Thirty-four patients were included in the study (n =
      17/group). Respectively, the Experimental Group and Control Group comprised 41.2%
      and 58.9% women (p= 0.937), and had average ages of 55.5 and 55.8 years. In the
      Experimental group, ultrasonographic localization for mixed ground-glass nodules
      with CT values of -500 to -100 Hounsfield units had an efficacy of 87.5%. By
      contrast, the localization efficacy in Control Group was 20.0% (p=0.032).A single
      surgeon without prior experience performed intraoperative ultrasonography in 20
      cases, and the latter 10 procedures required significantly less time relative to
      the former 10 procedures (p=0.000). CONCLUSIONS: During RATS, the use of
      intraoperative ultrasonography as an "alternative finger" to "touch" and findthe
      accurate location of pulmonary nodules, especially mixed ground-glass nodules, is
      warranted.

PMID- 29197914
TI  - Testicular volume and elasticity changes in young children with undescended
      testes.
AB  - AIMS: To evaluate the differences and changes of testicular volume and elasticity
      in normal (NL) testes and undescended testes (UDTs) of children using shear wave
      elastography (SWE). MATERIALS AND METHODS: Testicular ultrasound images from
      children younger than 60 months old were retrospectively reviewed. Testicular
      volumes and elasticities were compared between the UDT group and NL group. In
      patients with unilateral UDT (uUDT), we also compared the values between uUDT and
      contralateral grossly normal (CGN) testis groups. RESULTS: There were 25 UDTs
      including 4 bilateral in the UDT groupand 54 normal testes in the NL group. While
      testicular volume was significantly smaller in UDT (vs. NL) and uUDT (vs. CGN)
      groups, the elasticity was not different. Testicular volume was positively
      correlated with age in both NL (r=0.474) and CGN (r=0.729) groups (p<0.001),
      while there was no correlation in the UDT group. Testicular stiffness showed
      negative correlation with age in the NL group (r=-0.390, p=0.004) and positive
      correlation in the UDT group (r=0.426, p=0.034). CONCLUSIONS:  Instead of
      increasing volume and decreasing stiffness of normal testes during development of
      the early 60 months, UDTsexhibited smaller volume and increasing stiffness. The
      CGN testes of uUDT patients showed increasing volume without stiffness change.

PMID- 29197915
TI  - The diagnostic value of shear wave elastography for parathyroid lesions and
      comparison with cervical lymph nodes.
AB  - AIMS: The aim of this study was to prospectively assess the feasibility of the
      Virtual Touch tissue imaging quantification (VTIQ) method of shear wave
      elastography (SWE) for the discrimination of parathyroid lesions and to compare
      the lesions' stiffness with that of cervical lymph nodes. MATERIALS AND METHODS:
      SWE using VTIQ was performed on 66 patients with 87 histopathologically proven
      parathyroid lesions (54 parathyroid adenomas and 33 parathyroid hyperplasia) and
      29 patients with 31 inflammatory cervical lymph nodes. The mean SWVs of the
      lesions were compared and receiver operating characteristic (ROC) curve analysis
      was used to evaluate diagnostic performance. RESULTS: The mean SWV of parathyroid
      adenomas (2.16+/-0.33 m/s) differed significantly from those of parathyroid
      hyperplasia and lymph nodes (1.75+/-0.28 m/s and 1.86+/-0.37 m/s respectively,
      p<0.001). Selecting a cutoff value of 1.92 m/s for diagnosing adenoma led to 80%
      sensitivity and 82% specificity (area under the curve [AUC]: 0.832 [95%
      confidence interval (CI): 0.742-0.921], p< 0.001). CONCLUSIONS: The VTIQ method
      of SWE can contribute to the differentiation of parathyroid adenoma from
      parathyroid hyperplasia and cervical lymphnodes.

PMID- 29197916
TI  - An investigation into the variability between different shear wave elastography
      systems in muscle.
AB  - AIMS: The reliability and agreement between shear wave elastography (SWE) systems
      using different acquisition methods in muscles is not yet established. The
      objectives were to determine the reliability of a new SWE system on normal
      resting muscles using different acquisition methods and to compare its
      performance to an established state-of-the-art system. MATERIALS AND METHODS:
      Small, medium and large ROI sizes in addition to longitudinal, oblique and
      transverse orientations over five different locations within the rectus femoris
      muscle were tested using the new system. Results were compared to the established
      system to test for inter-system reproducibility. RESULTS: Lowest within-subject
      coefficient of variance (4.3%) andshear wave velocity (1.83 m/s) were associated
      with the medium ROI and longitudinal orientation from the lateral location. This
      combination resulted in a strong internal agreement of intra-class correlation of
      0.76 (0.57-0.89) for the new system and an almost perfect agreement of 0.92 (0.82
      0.97) for the established. Inter-system reproducibility for the best combination
      was 0.71 (0.48-1) with a mean velocity difference +/-95% limits of agreement of
      0.07+/-0.49 m/s. CONCLUSIONS: Altering SWE acquisition methods can produce
      variable results. The new system produced reliable results that are comparable
      with but not as reliable as the established.

PMID- 29197917
TI  - Romanian National Guidelines on Contrast Enhanced Ultrasound in clinical
      practice.
AB  - Contrast-enhanced ultrasound (CEUS) allows a real-time assessment of the vascular
      pattern of different types of lesions, as it has no renal or liver toxicity, it
      lacks radiation exposure and it is also cheaper than other imaging methods,
      having a diagnostic capability that matches contrast-enhanced CT or MRI. In
      Romania CEUS is used more and more, especially by clinicians, and since some
      centres have extensive experience in this domain, we felt the need to disseminate
      our expertise in order to implement this method in as many centres as possible.
      These Guidelines present the clinical applications of CEUS in the liver, spleen,
      pancreas, kidney, testis, bowel, intra-cavitary and endoscopic ultrasound, as
      well as other applications.

PMID- 29197918
TI  - The potential of ultrasonography in the evaluation of foot orthotics therapy.
AB  - Foot orthotics prescription is based on the foot functioning paradigms with
      tissue stress theory being in avant-garde. The main goal of orthotic therapy is
      to reduce the internal tissue's pathological stresses in the foot structures.
      Traditionally, ultrasound scanning technique depicts anatomic related data of
      both common and uncommon pathology encountered in the clinical practice, helping
      in diagnosing, treating and evaluating, which are equally important for the
      practitioners. Its accessibility, compared to biomechanical modelling, makes this
      technique a valuable tool in the field of foot and ankle disorders. Despite its
      user-dependent limitation, the ongoing technical progress improves the ability of
      ultrasonography as a highly advanced procedure in musculoskeletal imaging, being
      also a valuable searching tool for musculotendinous mechanics or morphological
      changes as a result of a conservative intervention. The aim of the present work
      was to perform a review of the state of the art concerning the usefulness of
      ultrasonography in the study of foot orthotic therapy and to analyze its
      effectiveness.

PMID- 29197919
TI  - Prostate ultrasound: back in business!
AB  - The use of grey scale prostate ultrasound decreased after the implementation of
      magnetic resonance imaging (MRI) for the diagnosis and evaluation of prostate
      cancer. The new developments, such as multiparametric ultrasound and MRI
      ultrasound fusion technology, renewed the interest for this imaging method in the
      assessment of prostate cancer. The purpose of this paper was to review the
      current role of prostate ultrasound in the setting of these new applications. A
      thorough reevaluation of the selection criteria of the patients is required to
      assess which patients would benefit from multiparametric ultrasound, who
      wouldbenefit from multiparametric MRI or the combination of both to assist
      prostate biopsy in order to ensure the balance between overdiagnosis and
      underdiagnosis of prostate cancer.

PMID- 29197920
TI  - Abdominal wall endometriosis: an update in clinical, imagistic features, and
      management options.
AB  - Abdominal wall endometriosis (AWE) is a rare condition defined by the presence of
      endometrial tissue in the subcutaneous fatty layer and the muscles of the
      abdominal wall. It is usually caused by the dissemination of endometrial tissue
      in the wound at the time of obstetrical and gynecological surgeries. AWE is rare
      and difficult to diagnose. The most frequent clinical presentation is that of a
      palpable subcutaneous mass near surgical scars associated with cyclic pain and
      swelling during menses. AWE may be an underreported pathology partly because it
      has scarcely received attention in the radiologic literature. Its frequency is
      expected to rise along with the increasing rate of cesarean deliveries; thus, it
      is important that physicians or sonographers are familiar with this pathology.
      The purpose of our review is to present the latest data regarding risk factors,
      clinical and imagisticfindings, and management of AWE.

PMID- 29197921
TI  - Enthesitis of the hands in psoriatic arthritis: an ultrasonographic perspective.
AB  - Psoriatic arthritis is a systemic inflammatory disease in which enthesitis and
      dactylitis are two of the main hallmarks of the disease. In the last years,
      ultrasonography is increasingly playing a key role in the diagnosis of psoriatic
      arthritis and ultrasonography of the entheses, particularly of the lower limbs,
      is commonly used to assess patients with that disease. New advancements in
      ultrasound equipment using high frequencies probes allowed us also to identify
      and characterize the involvementof the entheses of the hand in psoriatic
      arthritis, confirming the results of the experimental models of the disease and
      the theory of the sinovial-entheseal complex, even in small joints.

PMID- 29197922
TI  - Three-dimensional ultrasound and HDlive in tubal serous cystadenofibroma: a case
      report and literature review.
AB  - Cystadenofibromas of the fallopian tubes are very rare benign tumors and very few
      cases have been reported in the literature worldwide. Usually, the tumor is
      asymptomatic, and for almost all cases reported, the tumors were incidentally
      discovered during surgery for other genital pathology. We report the case of a 30
      year-old woman with a serous cystadenofibroma of the fallopian tube, presenting
      with chronic abdominal pain and secondary infertility. The diagnosis of tubal
      tumor was formulated before surgery and confirmed during laparoscopic surgery.
      Both 3D ultrasound and HDlive were useful tools for the diagnosis. The ultrasound
      diagnosis was helpful in planning appropriate surgical management.

PMID- 29197923
TI  - A rare case of an acute soleus arcade syndrome complicated by a ganglion cyst:
      diagnosis by dynamic ultrasound.
AB  - The soleus arcade syndrome is a rare compression neuropathy of the tibial nerve
      that often remains undiagnosed due to low clinical awareness and difficult
      diagnosis. We present the case of a female patient admitted with acute worsening
      of a pre-existing sensory tibial neuropathy and acute tibial nerve palsy after
      knee joint injection. After a knee magnetic resonance imaging remained non
      diagnostic, dynamic ultrasonography was performed. Constriction by the soleus
      arcade and proximal swelling of the tibial nerve could be demonstrated during
      plantarflexion of the ankle by means of a dynamic examination in the standing
      patient. The patient underwent surgery and recovered fully. This proposed
      diagnostic approach can be used to identify soleus arcade syndrome by ultrasound.

PMID- 29197924
TI  - Echocardiography as the first diagnostic clue to rapidly progressive systemic AL
      amyloidosis associated with multiple site thrombosis. A case report.
AB  - AL-amyloidosis is a rare, but complex disease, with a severe prognosis, cardiac
      involvement being found in half of the patients. The rapid increase of the LV
      wall thickness predicts an unfavorable evolution. We report the case of a 63-year
      old man diagnosed with AL-amyloidosis, with cardiac involvement, associated with
      multiple site thrombosis.  Specific echocardiographic methods like tissue Doppler
      imaging and speckle tracking provided crucial diagnostic and prognostic
      information.

PMID- 29197925
TI  - Imaging and histology in the diagnosis of multiple papillary fibroelastomas in a
      patient with hypertrophic obstructive cardiomyopathy. Case report.
AB  - Papillary fibroelastomas (PFEs) are one of the most frequent primary cardiac
      tumors and occur more often in patients with hypertrophic obstructive
      cardiomyopathy (HOCM). PFEs have been linked to an increased risk of neurological
      events. We report a case of a 59-year-old woman with HOCM in whom
      echocardiography (transthoracic and transesophageal, using 2D and 3D techniques)
      revealed multiple masses in various locations in the left cardiac chambers.
      Surgical excision of the cardiac tumors and aortic valve replacement was
      performed and the pathologic report confirmed the diagnosis of PFEs. Patient
      followup using ultrasonography is crucial since recurrence is a possibility.
      Current cardiac ultrasound techniques are essential for diagnosing and for
      guiding the management of these conditions.

PMID- 29197926
TI  - Masson's tumor and calcifying aponeurotic fibroma: two rare softtissue lesions in
      the same finger. High-resolution ultrasound features with histopathological
      correlations.
AB  - .

PMID- 29197927
TI  - A Novel Approach for Ultrasound Guided Axillary Nerve Block: The Inferior Axilla
      Technique.
AB  - .

PMID- 29197928
TI  - Non-fresh formaldehyde-embalmed cadaver: not an eligible model for Ultrasound
      Guided Sacroiliac Joint Injection studies.
AB  - N/A.

PMID- 29197929
TI  - Transdiagnostic Symptom Clusters and Associations With Brain, Behavior, and Daily
      Function in Mood, Anxiety, and Trauma Disorders.
AB  - Importance: The symptoms that define mood, anxiety, and trauma disorders are
      highly overlapping across disorders and heterogeneous within disorders. It is
      unknown whether coherent subtypes exist that span multiple diagnoses and are
      expressed functionally (in underlying cognition and brain function) and
      clinically (in daily function). The identification of cohesive subtypes would
      help disentangle the symptom overlap in our current diagnoses and serve as a tool
      for tailoring treatment choices. Objective: To propose and demonstrate 1 approach
      for identifying subtypes within a transdiagnostic sample. Design, Setting, and
      Participants: This cross-sectional study analyzed data from the Brain Research
      and Integrative Neuroscience Network Foundation Database that had been collected
      at the University of Sydney and University of Adelaide between 2006 and 2010 and
      replicated at Stanford University between 2013 and 2017. The study included 420
      individuals with a primary diagnosis of major depressive disorder (n = 100),
      panic disorder (n = 53), posttraumatic stress disorder (n = 47), or no disorder
      (healthy control participants) (n = 220). Data were analyzed between October 2016
      and October 2017. Main Outcomes and Measures: We followed a data-driven approach
      to achieve the primary study outcome of identifying transdiagnostic subtypes.
      First, machine learning with a hierarchical clustering algorithm was implemented
      to classify participants based on self-reported negative mood, anxiety, and
      stress symptoms. Second, the robustness and generalizability of the subtypes were
      tested in an independent sample. Third, we assessed whether symptom subtypes were
      expressed at behavioral and physiological levels of functioning. Fourth, we
      evaluated the clinically meaningful differences in functional capacity of the
      subtypes. Findings were interpreted relative to a complementary diagnostic frame
      of reference. Results: Four hundred twenty participants with a mean (SD) age of
      39.8 (14.1) years were included in the final analysis; 256 (61.0%) were female.
      We identified 6 distinct subtypes characterized by tension (n=81; 19%), anxious
      arousal (n=55; 13%), general anxiety (n=38; 9%), anhedonia (n=29; 7%),
      melancholia (n=37; 9%), and normative mood (n=180; 43%), and these subtypes were
      replicated in an independent sample. Subtypes were expressed through differences
      in cognitive control (F5,383 = 5.13, P < .001, etap2 = 0.063), working memory
      (F5,401 = 3.29, P = .006, etap2 = 0.039), electroencephalography-recorded beta
      power in a resting paradigm (F5,357 = 3.84, P = .002, etap2 = 0.051),
      electroencephalography-recorded beta power in an emotional paradigm (F5,365 =
      3.56, P = .004, etap2 = 0.047), social functional capacity (F5,414 = 21.33, P <
      .001, etap2 = 0.205), and emotional resilience (F5,376 = 15.10, P < .001, etap2 =
      0.171). Conclusions and Relevance: These findings offer a data-driven framework
      for identifying robust subtypes that signify specific, coherent, meaningful
      associations between symptoms, behavior, brain function, and observable real
      world function, and that cut across DSM-IV-defined diagnoses of major depressive
      disorder, panic disorder, and posttraumatic stress disorder.

PMID- 29197931
TI  - Effects of supervised exercise training on lower-limb cutaneous microvascular
      reactivity in adults with venous ulcers.
AB  - PURPOSE: To investigate the effects of a 12-week supervised exercise programme on
      lower-limb cutaneous microvascular reactivity in adults with venous leg
      ulceration. METHODS: Thirty-eight adults with unilateral venous ulceration who
      were being treated with lower-limb compression therapy (58% male; mean age 65
      years; median ulcer size 5 cm2) were randomly allocated to exercise or control
      groups. Exercise participants (n = 18) were invited to attend thrice weekly
      sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous
      microvascular reactivity was assessed in the gaiter region of ulcerated and non
      ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled
      with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP).
      Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux
      (AU)/mean arterial pressure (mmHg). RESULTS: Thirty-seven participants completed
      follow-up assessments. Median session attendance was 36 (range 2-36). Analyses of
      covariance revealed greater peak CVC responses to ACh in the exercise group at 3
      months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504
      1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028
      1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at
      3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274
      1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95%
      CI - 0.377 to 1.161). CONCLUSION: Supervised exercise training improves lower
      limb cutaneous microvascular reactivity in adults with venous leg ulceration.

PMID- 29197932
TI  - Evaluation of the anti-inflammatory effect of an anti-platelet agent crinumin on
      carrageenan-induced paw oedema and granuloma tissue formation in rats.
AB  - The present study was designed to explore the anti-inflammatory activity of an
      anti-platelet agent crinumin, by various in vitro and in vivo inflammation
      models. Firstly, crinumin protein was purified through cation exchange
      chromatography; then, in vitro activity was estimated by albumin denaturation
      assay and HRBC membrane stabilization assay. Carrageenan-induced paw oedema and
      cotton pellet-induced granuloma models were used for in vivo anti-inflammatory
      activity assessment in rats. In both models, rats were pre-treated for 7 days
      with crinumin (25-50 ug/ml) and diclofenac sodium (50 ug/ml). Expression of P
      selectin (in serum and plasma) through ELISA and NF-kappaB (in paw and
      granulomatous tissues) through western blotting was checked. Our results showed
      that crinumin at both doses (25 or 50 ug/kg of b.w.) significantly (p < 0.05)
      reduced the paw oedema formation in a dose-dependent manner in the second phase
      of inflammation and significant (p < 0.05) reduction of wet and dry weight of
      granuloma was observed indicating the anti-inflammatory potential of crinumin.
      Crinumin decreased the expression of P-selectin and NF-kappaB indicating its
      potential role in decreasing platelet activation and healing inflammation.
      Histopathological studies additionally proved the efficacy of drug in treating
      inflammation. The results of the study suggest that the crinumin might have an
      inhibitory role in atherosclerosis as platelet aggregation and inflammation are
      the key processes involved in atherosclerotic disorders.

PMID- 29197933
TI  - Impact of low-dose steroids on HbA1c levels and development of pre-diabetes and
      NODAT in non-diabetic renal transplant recipients on long-term follow-up.
AB  - BACKGROUND: This study aimed to evaluate the impact of 5 mg of prednisolone/day
      on HbA1c levels and its association with the development of pre-diabetes and new
      onset diabetes mellitus (NODAT) in non-diabetic first renal transplant recipients
      on long-term follow-up. METHODS: Four hundred patients were analysed on an
      average of 4.1 +/- 3.0 years after successful transplantation: 96 (24%) were
      steroid-free and 304 (76%) treated with 5 mg of prednisolone/day combined with
      cyclosporine A (CsA) or tacrolimus (Tac) as part of their immunosuppressive
      protocol. Pre-diabetes and NODAT were defined based on the HbA1c levels according
      to the current ADA guidelines. The Mann-Whitney U test and the Chi-square test
      were used to determine intergroup differences. Multivariate logistic regression
      analyses (adjusted for steroid-free versus 5 mg of prednisolone per day, body
      mass index (BMI), number of HLA mismatches, eGFR according to the CKD-EPI
      formula, sex, negative vs. positive PRA titre, CMV and HCV positivity of the
      recipient, CsA vs. Tac immunosuppressive medication, dialysis vintage (years),
      age at the last follow-up and time from transplantation to the last follow-up)
      were performed to identify an independent effect of low-dose steroids on the
      evolution of pre-diabetes and NODAT. RESULTS: A small but statistically
      significant difference in HbA1c levels was observed between the control and the
      steroid groups (5.56 +/- 0.54 vs. 5.67 +/- 0.0.45%, p = 0.045). The incidence
      rates of pre-diabetes and NODAT per 100 patients per year were 9.3 and 3.0,
      respectively. Regression analysis showed that low-dose steroids (p = 0.026, risk
      ratio (RR) 1.789, 95%; confidence interval (CI) 1.007-3.040) and age (p = 0.000,
      RR 1.037/year, 95% CI 1.018-1.057) were associated with pre-diabetes, whereas BMI
      (p = 0.000, RR 1.190, 95% CI 1.084-1.307), age (p = 0.000, RR 1.087/year, 95% CI
      1.047-1.129) and Tac use (p = 0.010, RR 3.300, 95% CI 1.328-8.196) were
      associated with NODAT. CONCLUSION: Using 5 mg of prednisolone/day was associated
      with increased HbA1c levels and an increased risk in developing pre-diabetes, but
      not NODAT, whereas BMI, age and the use of tacrolimus were associated with an
      increased risk in developing NODAT.

PMID- 29197934
TI  - Effects of statin treatment with atorvastatin on urolithiasis-associated urinary
      metabolic risk factors: an experimental study.
AB  - PURPOSE: To investigate whether atorvastatin has favorable effects on urinary
      metabolic risk factors associated with urolithiasis. METHODS: Sixteen male
      Sprague-Dawley rats were randomly divided into two groups, and baseline spot and
      24-h urine samples were collected. Distilled water and atorvastatin were
      administered to rats during 4 weeks in the control and atorvastatin groups,
      respectively. At the end of the experimental procedure, spot and 24-h urine
      samples were collected again. Citrate, oxalate, cystine, uric acid, calcium and
      magnesium levels were determined in 24-h urine samples. Citrate/creatinine,
      oxalate/creatinine, uric acid/creatinine, calcium/creatinine and
      magnesium/creatinine ratios were also calculated in spot urine samples.
      Comparison of the baseline and post-experimental levels of these parameters was
      made in each group. RESULTS: The majority of the parameters were similar before
      and after the experimental procedure in each group. In the atorvastatin group,
      uric acid and calcium levels were affected. Administration of atorvastatin was
      significantly decreased the levels of uric acid, whereas increased the levels of
      calcium (P = 0.025 and P = 0.017, respectively). CONCLUSIONS: Our study revealed
      that atorvastatin has decreasing effect on UUa levels, whereas increasing effect
      on UCa levels. We think it cannot certainly be deduced that atorvastatin could be
      beneficial on overall urinary metabolic risk factors. Contrarily, atorvastatin
      may lead to an increased risk of calcium stones, but when considering its UUa
      decreasing effect, it may help in reducing the uric acid stone recurrence.

PMID- 29197930
TI  - The PPARalpha-dependent rodent liver tumor response is not relevant to humans:
      addressing misconceptions.
AB  - A number of industrial chemicals and therapeutic agents cause liver tumors in
      rats and mice by activating the nuclear receptor peroxisome proliferator
      activated receptor alpha (PPARalpha). The molecular and cellular events by which
      PPARalpha activators induce rodent hepatocarcinogenesis have been extensively
      studied elucidating a number of consistent mechanistic changes linked to the
      increased incidence of liver neoplasms. The weight of evidence relevant to the
      hypothesized mode of action (MOA) for PPARalpha activator-induced rodent
      hepatocarcinogenesis is summarized here. Chemical-specific and mechanistic data
      support concordance of temporal and dose-response relationships for the key
      events associated with many PPARalpha activators. The key events (KE) identified
      in the MOA are PPARalpha activation (KE1), alteration in cell growth pathways
      (KE2), perturbation of hepatocyte growth and survival (KE3), and selective clonal
      expansion of preneoplastic foci cells (KE4), which leads to the apical event
      increases in hepatocellular adenomas and carcinomas (KE5). In addition, a number
      of concurrent molecular and cellular events have been classified as modulating
      factors, because they potentially alter the ability of PPARalpha activators to
      increase rodent liver cancer while not being key events themselves. These
      modulating factors include increases in oxidative stress and activation of NF-kB.
      PPARalpha activators are unlikely to induce liver tumors in humans due to
      biological differences in the response of KEs downstream of PPARalpha activation.
      This conclusion is based on minimal or no effects observed on cell growth
      pathways and hepatocellular proliferation in human primary hepatocytes and
      absence of alteration in growth pathways, hepatocyte proliferation, and tumors in
      the livers of species (hamsters, guinea pigs and cynomolgus monkeys) that are
      more appropriate human surrogates than mice and rats at overlapping dose levels.
      Despite this overwhelming body of evidence and almost universal acceptance of the
      PPARalpha MOA and lack of human relevance, several reviews have selectively
      focused on specific studies that, as discussed, contradict the consensus opinion
      and suggest uncertainty. In the present review, we systematically address these
      most germane suggested weaknesses of the PPARalpha MOA.

PMID- 29197936
TI  - Spontaneous irreducible urethral prolapse in a post-menopausal woman: a rare
      differential diagnosis of an intralabial mass.

PMID- 29197935
TI  - How to Improve Effectiveness and Adherence to Antihypertensive Drug Therapy:
      Central Role of Dihydropyridinic Calcium Channel Blockers in Hypertension.
AB  - Essential hypertension is a complex clinical condition, characterized by multiple
      and concomitant abnormal activation of different regulatory and contra-regulatory
      pathophysiological mechanisms, leading to sustained increase of blood pressure
      (BP) levels. Asymptomatic rise of BP may, indeed, promote development and
      progression of hypertension-related organ damage, which in turn, increases the
      risk of major cardiovascular and cerebrovascular events. A progressive and
      independent relationship has been demonstrated between high BP levels and
      increased cardiovascular risk, even in the high-to-normal range. Conversely,
      evidence from randomized controlled clinical trials have independently shown that
      lowering BP to the recommended targets reduces individual cardiovascular risk,
      thus improving event-free survival and reducing the incidence of hypertension
      related cardiovascular events. Despite these benefits, overall rates of BP
      control remain poor, worldwide. Currently available guidelines support a
      substantial equivalence amongst various antihypertensive drug classes. However,
      several studies have also reported clinically relevant differences among
      antihypertensive drugs, in terms of both BP lowering efficacy and
      tolerability/safety profile. These differences should be taken into account not
      only when adopting first-line antihypertensive therapy, but also when titrating
      or modulating combination therapies, with the aim of achieving effective and
      sustained BP control. This review will briefly describe evidence supporting the
      use of dihydropyridinic calcium channel blockers for the clinical management of
      hypertension, with a particular focus on barnidipine. Indeed, this drug has been
      demonstrated to be effective, safe and well tolerated in lowering BP levels and
      in reducing hypertension-related organ damage, thus showing a potential key role
      for improving the clinical management of hypertension.

PMID- 29197937
TI  - Parapharyngeal neuroglial heterotopia appearing as high uptake on 18F-FDG PET:
      case report and literature review of radiographical findings.
AB  - Parapharyngeal neuroglial heterotopia is a rare entity, and the specific
      radiographical findings are unclear. We present a case of parapharyngeal
      neuroglial heterotopia examined with proton magnetic resonance spectroscopy (1H
      MRS) and 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET). Our
      neonate patient presented with neck mass and polyhydramnios during gestation.
      Computed tomography and magnetic resonance imaging demonstrated the morphological
      characteristics, but failed to establish the diagnosis. 1H-MRS showed a non
      malignant pattern, but 18F-FDG PET demonstrated high glucose metabolism. Complete
      resection was achieved and the histopathological diagnosis was neuroglial
      heterotopia. Assessment of biological activity may be useful for both
      preoperative diagnosis and postoperative evaluation of residual lesions.

PMID- 29197938
TI  - Suppression of wheat TaCDK8/TaWIN1 interaction negatively affects germination of
      Blumeria graminis f.sp. tritici by interfering with very-long-chain aldehyde
      biosynthesis.
AB  - KEY MESSAGE: Wheat TaCDK8 interacts with TaWIN1 to regulate very-long-chain
      aldehyde biosynthesis required for efficient germination of Blumeria graminis
      f.sp. tritici. Powdery mildew caused by Blumeria graminis f.sp. tritici (Bgt) is
      a devastating disease of common wheat (Triticum aestivum L.). Bgt infection
      initiates with its conidia germination on the aerial surface of wheat. In this
      study, we isolated the cyclin-dependent kinase 8 (TaCDK8) from wheat cultivar
      Jing411 and found that silencing of TaCDK8 impeded Bgt germination. The
      biochemical and molecular-biological assays revealed that TaCDK8 interacts with
      and phosphorylates the wheat transcription factor wax inducer 1 (TaWIN1) to
      stimulate the TaWIN1-dependent transcription. Bgt conidia on the leaves of TaWIN1
      silenced plants also showed reduced germination. Gas chromatographic analysis
      revealed that knockdown of TaCDK8 or TaWIN1 resulted in decreases of wax
      components and cutin monomers in wheat leaves. Moreover, Bgt germination on
      leaves of TaCDK8 or TaWIN1 silenced plants could be fully restored by application
      of wild-type cuticular wax. In vitro studies demonstrated that very-long-chain
      aldehydes absent from the cuticular wax of the TaCDK8 or TaWIN1 silenced plants
      were capable of chemically stimulating Bgt germination. These results implicated
      that the suppression of TaCDK8/TaWIN1 interaction negatively affects Bgt
      germination by interfering with very-long-chain aldehyde biosynthesis required
      for efficient fungal germination.

PMID- 29197939
TI  - Postmortem angiography revealing traumatic rupture of the intracranial internal
      carotid artery.
AB  - Diagnosis of traumatic subarachnoid hemorrhage (SAH), although relatively rare,
      is important in forensic medicine. It is mostly associated with rupture of the
      vertebrobasilar artery. Traumatic aneurysm of the intracranial part of the
      internal carotid artery (ICA) is also rare but has been reported in several
      studies. It is thought that the intracranial ICA is injured by blunt force to the
      head, neck, and chest. However, traumatic SAH with fatal acute course resulting
      from rupture of the ICA is especially uncommon: only two fatal cases without an
      associated aneurysm have been reported in the English-language literature.
      Although detecting the arterial lesion is required to make a precise diagnosis,
      this is sometimes impossible by macroscopic examination at autopsy or by
      investigation after formalin-fixation according to the position of the lesion. We
      report a rare case of fatal traumatic SAH associated with intracranial ICA
      rupture. Postmortem computed tomography angiography was useful to confirm the
      lesion.

PMID- 29197940
TI  - Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through
      Mitigating the Activation of JAK2/STAT3 Pathway.
AB  - BACKGROUND: Thymoquinone (TQ) is the major constituent of Nigella sativa seed and
      has shown biological activity in various human carcinomas. However, few studies
      have reported its effect on esophageal carcinoma (EC). AIMS: To explore the
      chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)
      induced apoptosis of EC, both in vitro and in vivo. METHODS: The viability and
      apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8
      assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2,
      p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were
      evaluated by western blot analysis. The histological changes were examined by
      TUNEL technique and immunohistochemical analysis. RESULTS: TQ enhanced the
      proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while
      blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of
      esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3
      by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro
      results, TQ increased cellular apoptosis and enriched the chemosensitivity of
      DDP. CONCLUSIONS: TQ along with DDP may regulate the progression of EC and has
      potential to be a chemotherapeutic agent in EC.

PMID- 29197941
TI  - Heterogeneous functional expression of the sustained inward Na+ current in guinea
      pig sinoatrial node cells.
AB  - The sustained inward Na+ current (I st) identified in the sinoatrial node (SAN)
      cell has been suggested to play a pivotal role in cardiac pacemaking. However,
      the composition of cells in the SAN is heterogeneous and cell-to-cell variability
      in the magnitude of I st remains to be fully characterized. The present study
      investigated the current density of I st in morphologically different types of
      pacemaker cells dissociated from guinea pig SAN. I st was preferentially detected
      in spontaneously active spindle or spider-shaped cells, but was less well
      expressed in larger-sized elongated spindle-type cells and practically absent in
      clearly striated atrial-like cells, despite clear expression of the funny current
      (I f). The current density of I st in spindle and spider cells varied from 0.7 to
      1.6 pA pF-1 and was significantly reduced in non-beating cells with similar
      morphologies. By linear regression analysis, we identified a positive correlation
      between the current densities of I st and the L-type Ca2+ current (I Ca,L), which
      was specifically observed in spindle and spider cells. These cells exhibited a
      more negative voltage for half maximal I Ca,L activation than atrial-like cells,
      suggesting a variable ratio between CaV1.2- and CaV1.3-mediated I Ca,L in SAN
      cells. Consistent single-cell transcript measurements confirmed a higher relative
      expression of CaV1.3, which activates at more negative potentials, in spindle
      cells than in atrial-like cells. Taken together, these results can be interpreted
      as indicating that I st plays a specific role in primary pacemaker cells and that
      its presence is closely correlated with functional levels of CaV1.3-mediated I
      Ca,L.

PMID- 29197942
TI  - Five-year prevalence of recurrent shoulder dislocation in the entire Polish
      population.
AB  - PURPOSE: The aim of this study was to evaluate five-year prevalence of recurrent
      shoulder dislocation in the entire Polish population. METHODS: The study involved
      the entire Polish population between 01 January 2010 and 31 December 2014.
      Demographic data were retrieved from the Central Statistical Office of Poland.
      Data on the number of shoulder joint dislocations were retrieved from the
      database of the National Health Fund. RESULTS: We identified 32,253 Polish
      residents with shoulder instability. About 0.1% of Polish residents suffered from
      recurrent shoulder dislocation. Males suffered almost two times more often than
      females (66% and 34%, respectively), and male gender was recognized as a risk
      factor of instability (OR = 2.07, p <10-10). Females in their eighth decade of
      life had the highest risk of recurrent shoulder dislocation (OR = 3.33, p <10
      10). In males the highest risk of recurrences was noted for the third decade of
      life (OR = 1.78, p <10-10). CONCLUSION: The period prevalence rate of recurrent
      shoulder dislocation in Poland is 83.7 per 100,000 persons per five years. The
      rate of recurrent shoulder dislocation for the general Polish population is 0.1%.
      Males suffered from recurrent shoulder dislocation almost twice as frequently as
      females (OR = 2.07).

PMID- 29197943
TI  - Two-stage revision of infected shoulder arthroplasty using prosthesis of
      antibiotic-loaded acrylic cement: minimum three-year follow-up.
AB  - PURPOSE: This study aimed to evaluate the clinical outcomes and persistent
      infection rate of two-stage revision of infected shoulder arthroplasty. METHODS:
      We enrolled 12 patients who developed an infection after undergoing shoulder
      arthroplasty between January 2009 and January 2014. They underwent a two-stage
      revision with PROSTALAC implantation and shoulder re-implantation in the first-
      and second-stage surgery, respectively. The mean follow-up period was 40.88
      months (range, 36-52 months). After the second-stage re-implantation, clinical
      scores, erythrocyte sedimentation rate, as well as C-reactive protein level were
      evaluated, and the presence of re-infection and complications were analyzed.
      RESULTS: Infection was improved in all the cases after PROSTALAC insertion. The
      mean range of motion of forward elevation, external rotation, and internal
      rotation at the final follow-up after the second-stage re-implantation were 81.67
      degrees , 40.42 degrees , and 16.67 degrees  (vertebral level), respectively. The
      mean visual analog scale score improved from 7.08 points before surgery to 2.33
      points after surgery. The Modified American Shoulder and Elbow Surgeons score
      improved from 32.25 before surgery to 64.17 after surgery (P < 0.05). The
      Constant shoulder score also improved from 30.92 before surgery to 66.08 after
      surgery (P < 0.05). Infection had not recurred until the final follow-up.
      However, dislocation and separation of components were found in two patients who
      needed a structural allograft because of segmental bone defects. CONCLUSION:
      Using PROSTALAC in two-stage revision arthroplasty is effective for infection
      control and produced good clinical outcomes after second-stage shoulder re
      implantation. However, cases involving segmental bone defects require additional
      precautions in maintaining the appropriate tension and height to prevent
      complications.

PMID- 29197944
TI  - Experience of Symptoms and Disease Impact in Patients with Adenomyosis.
AB  - BACKGROUND: Adenomyosis is a poorly understood, benign disease of the uterus.
      OBJECTIVE: In this study, patient interviews were conducted to characterize the
      symptoms and impact of adenomyosis. METHODS: This was a cross-sectional study in
      which women with adenomyosis were recruited from five US clinics and a health
      related social network forum. Participants (aged 18-55 years) were pre-menopausal
      with a history of regular menstrual cycles. Participants were interviewed about
      their experiences with adenomyosis, symptoms and impacts on day-to-day activities
      (concept elicitation), and subsequently about the occurrence, relative severity,
      and impact of symptoms (card-sorting exercise). RESULTS: In total, 31 women were
      interviewed. Mean duration since onset of first adenomyosis symptom was 5.7
      years; 41.9% reported severe/very severe adenomyosis. Over 50 symptoms and 30
      impacts of adenomyosis were reported in the concept elicitation; 87% of symptoms
      were reported after 7 interviews and 78% of impacts after 5 interviews,
      indicating a condition with a significant symptom burden and a consistent
      presentation. The most common symptoms were heavy menstrual bleeding (87%),
      cramps (84%), and blood clots during menstrual bleeding (84%). The most common
      impacts were burdensome self-care hygiene (71%), and fatigue/low energy (71%). In
      the card-sorting exercise, the most commonly endorsed symptoms were pain during
      menstruation/menstrual cramps and heavy menstrual bleeding (both frequently rated
      as severe). The symptom with the highest impact was heavy menstrual bleeding.
      CONCLUSION: Initiatives to understand women's experiences with adenomyosis may
      improve management of the condition. This study provides a first step in
      understanding their experience and new information on the symptom profile of
      adenomyosis.

PMID- 29197945
TI  - Spontaneous expulsive suprachoroidal haemorrhage in an asymptomatic elderly
      patient: a case report.
AB  - PURPOSE: To describe a rare case of spontaneous expulsive suprachoroidal
      haemorrhage (SESCH) in an asymptomatic elderly patient. METHOD: This is a case
      report of a 76-year-old Chinese female, presented as an emergency with
      spontaneous left eye bleeding. She had underlying uncontrolled hypertension, no
      other systemic illness and not on anticoagulant. She has a history of right eye
      cataract operation, right eye angle-closure glaucoma and left eye absolute
      glaucoma complicated with painless left blind eye. Ocular examination over left
      eye showed no light perception and demonstrated presence of fresh bleed,
      expulsion of lens and prolapsed uveal contents, while right eye examination was
      unremarkable. Patient subsequently underwent evisceration and was uneventful.
      RESULTS: Routine blood investigations including coagulation profile came back as
      normal. Surgical findings include perforated cornea more than three-fourths with
      prolapsed uveal contents and fragile conjunctiva. No other significant
      macroscopic conditions were noted. Histology and culture came back with growth of
      Pseudomonas aeuroginosa with no evidence of malignancy. DISCUSSION: SESCH is a
      rare but serious sight-threatening ocular condition associated with multiple risk
      factors including arteriosclerosis, vascular disease, glaucoma, diabetes,
      intraocular malignancy and diseased eye wall. The predisposing factors involved
      in this case include advanced age, glaucoma with persistent high intraocular
      pressure, uncontrolled hypertension and presence of infection.

PMID- 29197946
TI  - First large genomic inversion in familial cerebral cavernous malformation
      identified by whole genome sequencing.
AB  - Familial cerebral cavernous malformations (CCMs) predispose to seizures and
      hemorrhagic stroke. Molecular genetic analyses of CCM1, CCM2, and CCM3 result in
      a mutation detection rate of up to 98%. However, only whole genome sequencing
      (WGS) in combination with the Manta algorithm for analyses of structural variants
      revealed a heterozygous 24 kB inversion including exon 1 of CCM2 in a 12-year-old
      boy with familial CCMs. Its breakpoints were fine-mapped, and quantitative
      analysis on RNA confirmed reduced CCM2 expression. Our data expand the spectrum
      of CCM mutations and indicate that the existence of a fourth CCM disease gene is
      rather unlikely.

PMID- 29197947
TI  - Effects of a dialectical behavior therapy-based skills group intervention for
      obese individuals: a Brazilian pilot study.
AB  - PURPOSE: This pilot study aimed to analyze the effects of an adapted dialectical
      behavior therapy (DBT) skills training group on problematic and adaptive eating
      behaviors in Brazilian obese individuals. METHODS: Thirty-one obese individuals
      were randomly assigned to 10 sessions of adapted DBT skills training (n = 14) or
      two months of a waiting list comparison condition (n = 17). RESULTS: Attrition
      rates were similar to what's been found in comparable studies, with most dropouts
      happening at the beginning of the treatment. Results showed improvements in binge
      eating severity (d = 0.80) and depression (d = 0.82) compared to no treatment
      condition. After the intervention, adaptive eating and distress outcomes showed
      an improvement trend, reaching nonclinical levels for most participants in the
      intervention group. Large to moderate between-group effect sizes were observed,
      but none of those were statistically significant. Large within-group effect sizes
      were observed in the intervention group in binge eating severity (d = 1.34),
      intuitive eating (d = 1.33) and depression (d = 1.12). Medium effect sizes were
      observed in emotional eating (d = 0.73) and in emotion regulation (d = 0.72).
      Despite positive outcomes in other variables, mindful eating worsened after the
      intervention (d = 0.66). CONCLUSIONS: These results are preliminary and require
      further replications with larger samples, yet they suggest that the intervention
      may be useful to improve distress outcomes and adaptive eating among obese
      people. Implications for clinical practice and recommendations for future
      research are discussed. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

PMID- 29197948
TI  - Injury potential of thrown sharp kitchen and household utensils.
AB  - We examined the possibility of inflicting serious injuries with sharp objects in
      an experimental setting by throwing four sharp objects from different distances
      and with different throwing techniques. Using an overarm-handle (OA/H), overarm
      blade (OA/B), underarm-handle (UA/H), underarm-blade (UA/B) and thrust (T/H)
      throwing technique, 10 adults (sex ratio 1:1) threw a chef's knife, a skinning
      knife, a paring knife and office scissors from 4 m and 2 m distance at synthetic
      abdomen models made of 10% gelatin covered with synthetic skin. The amount of
      hits and penetrations of the target and their penetration depth were noted, as
      was the rotation of the blade tip towards the target along its flight trajectory.
      The chef's knife injury/hit ratio was 0.167/4 m and 0.160/2 m; the skinning knife
      recorded an injury/hit ratio of 0.087/4 m and 0.153/2 m; the paring knife of
      0.087/4 m and 0.113/2 m; and the scissors 0.087/4 m and 0.067/2 m. Mean
      penetration depths were as follows: the chef's knife: 4 m, 4.42 cm, 2 m, 3.41 cm;
      the skinning knife: 4 m, 4.19 cm, 2 m, 4.11 cm; the paring knife: 4 m, 1.62 cm, 2
      m, 1.55 cm; and the scissors: 4 m, 2.08 cm, 2 m, 0.95 cm. Handle-throw
      penetration-depths were: 4 m: 3.77 cm and 2 m: 2.86 cm; blade-throw depths were:
      4 m: 3.14 cm and 2 m: 2.69 cm. Overarm-throw penetration-depths were: 4 m: 3.62
      cm and 2 m: 3.25 cm; and underarm-throw penetration-depths were 4 m: 3.30 cm and
      2 m: 2.30 cm. No thrust-throws with the paring knife and scissors could pierce
      the target. The tips pointed toward the target at angles of 60 degrees -120
      degrees , earlier in handle-throws than blade-throws, especially with the paring
      knife and the scissors. When thrown, especially with a handle-held technique,
      heavier objects pierced more often and more deeply. Thrust-throws at short
      distances are unlikely to pierce a human.

PMID- 29197949
TI  - A heart of stone: an autopsy case of massive myocardial calcification.
AB  - A case of massive calcification of the myocardium is presented that was diagnosed
      by postmortem computed tomography (PMCT) and confirmed by conventional autopsy.
      There are two types of pathologic calcification, dystrophic and metastatic.
      Massive calcification of the myocardium is associated with variable clinical
      outcomes, including sudden unexpected death. A 53-year-old man was found after he
      collapsed beside a walkway. He was transferred to hospital and died approximately
      two months later. To investigate the cause of death, PMCT and conventional
      autopsy were performed, which revealed massive calcification of the myocardium, a
      very rare finding at autopsy. Massive myocardial calcification was one of the
      possible causes of his collapse. PMCT may be a useful diagnostic tool for
      detecting massive calcification of the myocardium following sudden cardiac death.

PMID- 29197950
TI  - The P-type ATPase CtpG preferentially transports Cd2+ across the Mycobacterium
      tuberculosis plasma membrane.
AB  - P1B-type ATPases are involved in heavy metal transport across the plasma
      membrane. Some Mycobacterium tuberculosis P-type ATPases are induced during
      infection, suggesting that this type of transporter could play a critical role in
      mycobacterial survival. To date, the ion specificity of M. tuberculosis heavy
      metal-transporting P1B-ATPases is not well understood. In this work, we observed
      that, although divalent heavy metal cations such as Cu2+, Co2+, Ni2+, Zn2+ Cd2+
      and Pb2+ stimulate the ATPase activity of the putative P1B-type ATPase CtpG in
      the plasma membrane, whole cells of M. smegmatis expressing CtpG only tolerate
      high levels of Cd2+ and Cu2+. As indicator of the catalytic constant, Michaelis
      Menten kinetics showed that CtpG embedded in the mycobacterial cell membrane has
      a V max/K m ratio 7.4-fold higher for Cd2+ than for Cu2+ ions. Thus, although
      CtpG can accept different substrates in vitro, this P-type ATPase transports Cd2+
      more efficiently than other heavy metal cations across the mycobacterial plasma
      membrane.

PMID- 29197951
TI  - Epibiont growth on filamentous bacteria found in activated sludge: a
      morphological approach.
AB  - Occurrence of epibiont attachment on filamentous bacteria is a common phenomenon
      in activated sludge. In this study, an attempt has been made to elucidate the
      intrinsic nature of the attachment between the epibionts and filamentous bacteria
      based on microscopic observations. Characterization of the epiflora based on
      fluorescence in situ hybridization using group level probes revealed that the
      epibionts colonizing these filamentous bacteria largely belongs to the class
      Alphaproteobacteria, followed by Beta and Gammaproteobacteria. The
      ultrastructural examination using transmission electron microscopy pointed to the
      existence of a possible cell-to-cell interaction between epibionts and the
      selected filaments. Common bacterial appendages such as pili and fimbria were
      absent at the interface and further noted was the presence of cell membrane
      extensions on epibiont bacteria protruding towards the targeted filamentous cell.
      Fibrillar structures resembling amyloid-like proteins were observed within the
      filament cells targeted by the epibionts. An interaction was apparent between
      amyloid such as proteins and epibionts with regards to the direction of fibrillar
      structures and the distance of approaching epibiont bacteria. Due to the lack of
      visual evidence in support of penetration, the role of these amyloid-like fibrils
      as potential attachment sites for the epibionts was taken into consideration, and
      required further validation using conformational antibodies.

PMID- 29197952
TI  - First identification of L. major in a dog in an endemic area of human cutaneous
      leishmaniasis in Iraq: molecular and phylogenetic studies.
AB  - Canine leishmaniasis (CanL) caused by Leishmania infantum (L. infantum) is
      considered as a zoonotic disease and within the last few decades, studies have
      identified the parasite as a major causative agent of human visceral
      leishmaniasis. However, in dogs, few recent studies have determined L. major as a
      cause of cutaneous manifestations and L. tropica as an etiological agent for
      cutaneous lesions involving mucosa. Interestingly, current study has found canine
      cutaneous lesions with mucosal involvement in a dog diagnosed with L. major, for
      the first time, in a focused area of human cutaneous leishmaniasis (CL) in the
      borderline between northern and central Iraq. Both molecular and phylogenetic
      studies showed that the dog L. major strain is closely related to that previously
      isolated from human CL in the same area. Moreover, serological study using rK39
      identified IgG response against Leishmania, and the histological finding revealed
      the infiltration of inflammatory cells around the infection sites. These data
      will broaden our knowledge about CanL concerning the appearance of cutaneous
      clinical manifestations with mucocutaneous lesions caused by L. major. Further
      study on other animal reservoirs and vectors will shed the light on the
      epidemiology of this disease.

PMID- 29197953
TI  - Prolonged use of alendronate alters the biology of cranial repair in estrogen
      deficient rats' associated simultaneous immunohistochemical expression of TGF
      beta1+, alpha-ER+, and BMPR1B.
AB  - OBJECTIVES: TGF-beta1 is a cytokine that may induce both osteoneogenesis through
      Runx-2 or fibrosis via the transcription of alpha-smooth muscle actin (alpha
      SMA). Because it has been previously known that alendronate increases the level
      of TGF-beta1 and that under the usual condition of bone metabolism the estrogen
      may prevent the fibrotic effect of TGF-beta1, the aim of this study was to
      evaluate if alendronate alters the cellular differentiation process post
      calvarial surgery in estrogen-deficient specimens. MATERIALS AND METHODS: A
      transosseous defect that was 5 mm in diameter was created on the calvarium of
      each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects
      were treated with autografts, and 16 rats received the administration of 1 mg/kg
      of alendronate three times a week until euthanasia on the 15th and 60th day post
      surgery. Histomorphometric and immunohistochemical analyses of the expression of
      TGF-beta1, estrogen receptor alpha nuclear (alpha-ER), alpha-SMA, BMPR1B, and
      Runx-2 were performed, and ELISA was used to measure the level of estrogen.
      RESULTS: All animals demonstrated low levels of estrogen post ovarian-salpingo
      oophorectomy. The histological results demonstrated larger bone matrix deposition
      in specimens treated with alendronate on the 15th day post surgery. The result
      was associated with a higher co-expression of TGF-beta1, BMPR1B, and Runx-2 when
      compared with the control group. In addition, on the 60th day post surgery, the
      increase of bone matrix deposition from 15th to 60th day was discrete in
      specimens treated with alendronate compared with the control group. This result
      coincided with the intense simultaneous expression of TGF-beta1, alpha-ER, and
      alpha-SMA, whereas the expression of BMPR1B and Runx-2 decreased. CONCLUSION: The
      prolonged administration of alendronate altered the cranial repair in ovarian
      salpingo-oophorectomized specimens due to the simultaneous occurrence of low
      estrogen and the presence of TGF-beta1+/alpha-ER+ inducing the presence of alpha
      SMA+, whereas BMPR1B and Runx-2 were suppressed. CLINICAL RELEVANCE: The
      prolonged administration of alendronate alters osteoneogenesis and induces an
      unusual microenvironment in the bone that seems to imitate the physiological
      tissue damage that culminates in the loss of the functional layer of endometrium.

PMID- 29197954
TI  - A Latent Class Analysis of Gambling Activity Patterns in a Canadian University
      Sample of Emerging Adults: Socio-demographic, Motivational, and Mental Health
      Correlates.
AB  - This analysis of gambling habits of Canadian university students (ages 18-25)
      dovetails two recent developments in the field of gambling studies. First, the
      popularity of latent class analysis to identify heterogeneous classes of gambling
      patterns in different populations; second, the validation of the Gambling Motives
      Questionnaire (with financial motives) among university students-specifically to
      understand both how and why emerging adults gamble. Our results support a four
      class model of gambling activity patterns, consisting of female-preponderant
      casual and chance-based gambling groups, and male-preponderant skill-based and
      extensive gambling groups. Each class shows a specific combination of motives,
      underscoring the necessity for nuanced responses to problem gambling among
      emerging adults. More specifically, gambling for the skill-based group appears
      primarily to be a source of thrill and a way to cope; for the chance-based group,
      gambling appears but one symptom of a set of wider issues involving depression,
      anxiety, substance use, and low self-esteem; while extensive gamblers seem to
      seek excitement, sociality, and coping, in that order. Only the chance-based
      group was significantly more likely than casual gamblers to be motivated by
      financial reasons. Situating our analysis in the literature, we suggest that
      interventions for the predominantly male subtypes should address gambling
      directly (e.g. re-focusing excitement seeking into other activities, instilling
      more productive coping mechanisms) while interventions for predominantly female
      subtypes should address low self-esteem in conjunction with depression, substance
      abuse, and problematic levels of gambling. We conclude future research should
      focus on links between self-esteem, depression, substance abuse, and financial
      motives for gambling among female emerging adults.

PMID- 29197955
TI  - Effect of supplementation of indigenous browse tree pods on weight gain and
      carcass parameters of Abergelle rams.
AB  - The objective of the study was to evaluate the effect of supplementation of
      indigenous browse tree pods on nutrient intake, digestibility, weight gain, and
      carcass parameters of local Abergelle rams fed grass hay as a basal diet. This
      experiment was conducted at the Abergelle Agricultural Research Center farm in
      Tigray region, northern Ethiopia. Experimental rams were grouped according to
      their initial body weight (17.4 +/- 0.95 kg) in a randomized complete block
      design into three treatments and six replications. Treatments consisted of
      feeding grass hay free of choice supplemented with pods of either Acacia tortilis
      (T1), Faidherbia albida (T2), or Dichrostachys cinerea (T3) fed at the rate of 10
      g kg-1 body weight daily. The crude protein (CP) contents of the supplemental
      feeds in T1, T2, and T3 were 167, 156, and 135 g kg-1 dry matter (DM),
      respectively. The CP intake was significantly higher (P < 0.05) in T1 and T2 than
      that in T3. No statistical difference (P > 0.05) was observed in the
      digestibilities of DM and CP. Final body weight, average daily gain, slaughter
      weight (SW), hot carcass weight, and ribeye area were not significantly different
      (P > 0.05) among the treatments. However, dressing percentage based on SW in T1
      and T2 was significantly higher (P < 0.05) than that in T3. Therefore, from this
      research, it can be concluded that though the weight gains and carcass weights of
      experimental rams were not as such remarkable among the treatments, efficient
      utilization of locally available and cheap browse tree pods as alternative
      protein supplements to Abergelle sheep during the dry season could be important
      to small holder farmers.

PMID- 29197956
TI  - Comparative Effects of Biochar, Slag and Ferrous-Mn Ore on Lead and Cadmium
      Immobilization in Soil.
AB  - A variety of remediation approaches have been applied to the heavy metals
      contaminated soils, however, the immobilization of metals in co-contaminated
      soils still not cleared. Therefore, an incubation study was conducted to evaluate
      the instantaneous effects of different concentrations of biochar (BC), slag (SL)
      and Fe-Mn ore (FMO) on immobilization of Pb and Cd through the Toxicity
      Characteristic Leaching Procedure (TCLP) by following the the European Community
      Bureau of Reference (BCR), CaCl2 and NH4NO3. The sequential extraction of BCR
      showed decrease in acid soluble fractions, while the residual proportions of Pb
      and Cd were enhanced with increasing concentrations of SL and BC. Addition of BC
      significantly lowered the extractable fractions of both metals by TCLP, NH4NO3
      and CaCl2 as compared to SL and FMO. Among all amendments, BC incorporation into
      co-contaminated soil offered promising results for Pb and Cd immobilization.
      Overall, all amendments showed positive and long-term impact on the reclamation
      of co-contaminated soil with heavy metals and could deserve advance monitoring
      studies on a field scale.

PMID- 29197957
TI  - Magnetic resonance imaging follow-up of chondroid tumors: regression vs.
      progression.
AB  - OBJECTIVE: To present magnetic resonance imaging (MRI) evidence of the regression
      or progression of chondroid tumors and to investigate whether MRI can be used to
      predict the evolution of chondroid tumors. MATERIALS AND METHODS: Twenty-one
      patients with enchondromas or atypical cartilaginous tumors who had undergone
      extremity MRI at least twice with a minimum 12-month interval between the MRIs
      were enrolled in this study. The diagnosis was based on the radiography and MRI
      findings. We classified the tumors into the following three groups according to
      changes between the MRIs: no change (NC), progression (P), and regression (R). We
      assessed the initial MRI features, including anatomical location, size, endosteal
      scalloping, peritumoral edema, fat entrapment, and direction of progression or
      regression. Nineteen of the 21 patients had contrast-enhanced images, and we
      analyzed the presence of atypical lobular enhancement against typical peripheral
      or septal enhancement. RESULTS: The R group comprised 11 cases (52%), the P group
      comprised five cases (24%), and the NC group comprised five cases (24%). None of
      the MRI features showed statistically significant differences among the groups.
      Atypical lobular enhancement was observed in the R (6 of 10, 60%) and NC (2 of 5,
      40%) groups but not in the P group (0 of 4, 0%), although these differences were
      not statistically significant. CONCLUSIONS: Chondroid tumors can either regress
      or progress in the MRI follow-up. Atypical lobular enhancement was seen only in
      stable or regressing tumors.

PMID- 29197959
TI  - Fractures frequently occur in older cancer patients: the MD Anderson Cancer
      Center experience.
AB  - PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults
      aged 65 years and older. Patients with cancer are at increased risk for
      developing osteoporosis, falls, and fractures. We sought to identify the
      incidence of fractures in older adults who underwent cancer care between January
      2013 and December 2015. METHODS: A comprehensive geriatric assessment was
      performed, and bone densitometry was measured at baseline, with a 2-year follow
      up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic,
      breast, lung, and gynecologic cancers we evaluated, and who completed the bone
      density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia).
      There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p =
      0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was
      identified in 49% of tested cases (n = 245). Risk factors for low bone mass or
      osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty
      (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an
      incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than
      reported in individuals without cancer. Risk factors for fractures included
      advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03).
      CONCLUSION: Most older cancer patients studied have osteoporosis or low bone
      mass, resulting in an almost 3-fold increase in fracture risk as compared to
      epidemiologic studies. Bone health issues are commonly seen in older cancer
      patients, we recommend universal bone density testing. The initiation of
      antiresorptive treatment when findings are of osteopenia or osteoporosis will
      reduce the risk of fractures.

PMID- 29197958
TI  - Immunohaemostasis: a new view on haemostasis during sepsis.
AB  - Host infection by a micro-organism triggers systemic inflammation, innate
      immunity and complement pathways, but also haemostasis activation. The role of
      thrombin and fibrin generation in host defence is now recognised, and thrombin
      has become a partner for survival, while it was seen only as one of the
      "principal suspects" of multiple organ failure and death during septic shock.
      This review is first focused on pathophysiology. The role of contact activation
      system, polyphosphates and neutrophil extracellular traps has emerged, offering
      new potential therapeutic targets. Interestingly, newly recognised host defence
      peptides (HDPs), derived from thrombin and other "coagulation" factors, are
      potent inhibitors of bacterial growth. Inhibition of thrombin generation could
      promote bacterial growth, while HDPs could become novel therapeutic agents
      against pathogens when resistance to conventional therapies grows. In a second
      part, we focused on sepsis-induced coagulopathy diagnostic challenge and
      stratification from "adaptive" haemostasis to "noxious" disseminated
      intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual
      coagulation tests, we discussed cellular haemostasis assessment including
      neutrophil, platelet and endothelial cell activation. Then, we examined
      therapeutic opportunities to prevent or to reduce "excess" thrombin generation,
      while preserving "adaptive" haemostasis. The fail of international randomised
      trials involving anticoagulants during septic shock may modify the hypothesis
      considering the end of haemostasis as a target to improve survival. On the one
      hand, patients at low risk of mortality may not be treated to preserve
      "immunothrombosis" as a defence when, on the other hand, patients at high risk
      with patent excess thrombin and fibrin generation could benefit from available
      (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors)
      therapies. We propose to better assess coagulation response during infection by
      an improved knowledge of pathophysiology and systematic testing including
      determination of DIC scores. This is one of the clues to allocate the right
      treatment for the right patient at the right moment.

PMID- 29197960
TI  - Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the
      impact on muscle strength and physical performance.
AB  - PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an
      attritional impact on body composition and functional status, impacting
      postoperative outcome. Physical decline with skeletal muscle loss has not been
      previously characterised in OC and may be amenable to physical rehabilitation.
      This study characterises skeletal muscle mass and physical performance from
      diagnosis to post-neoadjuvant therapy in patients undergoing preoperative
      chemo(radio)therapy for OC. METHODS: Measures of body composition (axial
      computerised tomography), muscle strength (handgrip), functional capacity
      (walking distance), anthropometry (weight, height and waist circumference),
      physical activity, quality-of-life and nutritional status were captured
      prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass
      only), sarcopenic (low muscle mass and low muscle strength or function) or
      severely sarcopenic (low muscle mass and low muscle strength and low muscle
      function). RESULTS: Twenty-eight participants were studied at both time points
      (mean age 62.86 +/- 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95%
      confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to
      6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing
      gastrointestinal symptoms improved. Measures of anthropometry, walking distance,
      physical activity and nutritional status did not change. There was an increase in
      sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre
      sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of
      body weight, functional capacity and activity habits, participants experience
      declines in muscle mass and strength. Interventions involving exercise and/or
      nutritional support to build muscle mass and strength during preoperative
      therapy, even in patients who are functioning normally, are warranted.

PMID- 29197961
TI  - Burden of oral mucositis in stem cell transplant patients-the patients'
      perspective.
AB  - PURPOSE: Purpose of this study was to determine the impact of Oral Mucositis (OM)
      on health-related quality of life (HRQoL) and quality of life associated symptoms
      and functions in patients undergoing hematopoietic stem cell transplantation
      (HSCT). METHODS: Prospective, non-interventional single-center observational
      study at a German tertiary teaching hospital. Inpatient allogenic and autologous
      stem cell transplant patients >=18-year-old with high-dose chemotherapy. OM was
      assessed with the WHO Oral Toxicity Scale, pain according to the Numeric Rating
      Scale (NRS) and the performance status using the ECOG Score. QOL was captured
      with the EORTC QLQ-C30 and the QLQ-OH15 questionnaires. RESULTS: Forty-five stem
      cell transplant patients (20 autologous, 25 allogenic) were enrolled between
      August 2016 and February 2017. Twenty-six (58%, 95% CI: 42% - 72%) patients
      developed OM (10 grade I, 4 grade II, 8 grade III, 4 grade IV). OM affected
      patients suffered more from pain, sore mouth and sensitive mouth. A lower
      physical functioning (34.5 vs 7.5, p = 0.003) and a lower oral health-related
      quality of life (24.3 vs 7.7, p = 0.006) was found in patients with OM
      development. There was found a positive correlation between the grade of OM and
      the NRS-value (r = 0.93, 95% CI: 0.89-0.96, p < 0.001). CONCLUSION: OM is
      associated with health-related quality of life and quality of life associated
      functions and symptoms. More research should be performed to find ways to prevent
      OM and to stabilize patients' quality of life during HSCT.

PMID- 29197962
TI  - Structure-based pharmacophore design and virtual screening for novel potential
      inhibitors of epidermal growth factor receptor as an approach to breast cancer
      chemotherapy.
AB  - Cancer cells are described with features of uncontrolled growth, invasion and
      metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases
      (EGFR-TK) plays a crucial regulatory role in the control of cellular
      proliferation and progression of various cancers. Therefore, its inhibition might
      lead to the discovery of a new generation of anticancer drugs. In the present
      study, structure-based pharmacophore modeling, molecular docking and molecular
      dynamics simulations were applied to identify potential hits, which exhibited
      good inhibition on the proliferation of MCF-7 breast cancer cell line and
      favorable binding interactions on EGFR-TK. Selected compounds were examined for
      their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast
      cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and
      2, with an isoindoline-1-one core, induced significant inhibition of breast
      cancer cells proliferation with IC[Formula: see text] values 327 and 370 nM,
      respectively.

PMID- 29197963
TI  - Synthesis and biological evaluation of imidazo[1,2-[Formula: see
      text]]pyridazines as inhibitors of TNF-[Formula: see text] production.
AB  - Tumor necrosis factor-alpha (TNF-[Formula: see text] is an important pro
      inflammatory cytokine responsible for a diverse range of inflammatory diseases
      including rheumatoid arthritis. In the present manuscript, our medicinal
      chemistry efforts on the design, synthesis and TNF-[Formula: see text] evaluation
      of a series of 3, 6-disubstituted imidazo[1,2-b]pyridazine is described. The best
      compounds were 3-pyridyl and (4-(methylsulfonyl)phenyl) analogs 8q and 8w,
      showing inhibition of TNF-[Formula: see text] production with IC[Formula: see
      text]values of 0.9 and 0.4 [Formula: see text]M, respectively. The identified
      leads have potential for further development for treatment of inflammatory
      diseases.

PMID- 29197964
TI  - Cognitive assessment of older adults in general practice: the collateral history.
AB  - BACKGROUND: The collateral (or informant) history is a key component in the
      assessment of older adults presenting with a memory problem or concern over
      cognition. Despite this, it rarely features in medical literature and academic
      curricula. Its role in general practice has never been assessed. AIMS: The aim of
      this study is to assess the role of the collateral history in the investigation
      of cognitive impairment in general practice. METHODS: An online survey
      distributed to three nationally representative cohorts of GPs in Ireland (n =
      692). RESULTS: Ninety-five (14%; 52.2% male) responded. Nearly all (87%; 83/95)
      indicate that it is most often a family member who brings possible cognitive
      impairment to the attention of their GP. The vast majority obtain a collateral
      history in > 90% of cases (72.6%; 69/95) and rate it very useful in their
      clinical assessment of cognition. GPs report the collateral history as readily
      available and rarely refused, with the general practice environment well-suited
      to obtaining collateral histories. A small minority routinely use the GPCOG
      informant section (3.2%; 3/95). Nearly all (92.6%; 88/95) report having received
      no training in obtaining collateral histories with most (79%; 75/95) welcoming of
      further training in this area. CONCLUSIONS: Despite recognition of the utility
      and importance of the collateral history, the vast majority of GPs report having
      never received training in obtaining one and do not use structured tools to guide
      their interview. Further emphasis on the informant history as a distinct clinical
      entity on medical curricula and increasing emphasis on the availability of
      structured informant tools are warranted.

PMID- 29197965
TI  - Progress of statistical analysis in biomedical research through the historical
      review of the development of the Framingham score.
AB  - BACKGROUND: The interest in developing risk models in medicine not only is
      appealing, but also associated with many obstacles in different aspects of
      predictive model development. Initially, the association of biomarkers or the
      association of more markers with the specific outcome was proven by statistical
      significance, but novel and demanding questions required the development of new
      and more complex statistical techniques. METHODS: Progress of statistical
      analysis in biomedical research can be observed the best through the history of
      the Framingham study and development of the Framingham score. RESULTS: Evaluation
      of predictive models comes from a combination of the facts which are results of
      several metrics. Using logistic regression and Cox proportional hazards
      regression analysis, the calibration test, and the ROC curve analysis should be
      mandatory and eliminatory, and the central place should be taken by some new
      statistical techniques. In order to obtain complete information related to the
      new marker in the model, recently, there is a recommendation to use the
      reclassification tables by calculating the net reclassification index and the
      integrated discrimination improvement. Decision curve analysis is a novel method
      for evaluating the clinical usefulness of a predictive model. It may be noted
      that customizing and fine-tuning of the Framingham risk score initiated the
      development of statistical analysis. CONCLUSION: Clinically applicable predictive
      model should be a trade-off between all abovementioned statistical metrics, a
      trade-off between calibration and discrimination, accuracy and decision-making,
      costs and benefits, and quality and quantity of patient's life.

PMID- 29197966
TI  - Aetiological profile and treatment outcomes of epistaxis at a major teaching
      hospital: a review of 721 cases.
AB  - BACKGROUND: Epistaxis is the most prevalent ENT emergency and a significant
      burden on ENT services. Our objective was to study the incidence and outcomes of
      patients presenting with epistaxis at a major teaching hospital. METHODS: A
      retrospective descriptive study of 721 patients, who presented with epistaxis
      over a 1-year period, was carried out. Data collected was analysed using SPSS
      software version 20. RESULTS: Of the 721 patients, initial treatment consisted of
      nasal cautery (298), nasal packing (200), or no treatment (223). Fifty-nine
      patients were admitted. The mean age of admitted patients was 66.8 years and the
      male to female ratio was 2:1. 69.5% had hypertension and 78% used an
      antiplatelet/anticoagulation medication. The majority of admitted and return
      patients were out of hours referrals from ED and the mean admission duration was
      five nights. Surgical treatment for intractable epistaxis included arterial
      ligation or endovascular embolisation. Successful treatment was defined as no
      recurrent epistaxis following pack removal or no readmission with epistaxis
      within 24 h of hospital discharge. Six hundred forty-four patients had successful
      treatment. CONCLUSION: More return and admitted patients presented at out-of
      hours times with less clinical staff on site. Most non-admitted patients received
      no treatment. These factors possibly lead to increased stress on the ENT casualty
      service. Cautery and nasal packing are the most common treatment modalities in
      first-time and admitted patients yet result in considerable rates of
      representation.

PMID- 29197967
TI  - Effects of nutraceuticals on anaplastic thyroid cancer cells.
AB  - PURPOSE: The anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid
      cancer with a high mortality rate. Since nutraceuticals may exert beneficial
      effects on tumor biology, here, effects of four of these compounds [resveratrol,
      genistein, curcumin and epigallocatechin-3-gallate (EGCG)] on ATC cell lines were
      investigated. METHODS: Two ATC-derived cell lines were used: SW1736 and 8505C.
      Cell viability and in vitro aggressiveness was tested by MTT and soft agar
      assays. Apoptosis was investigated by Western Blot, using an anti-cleaved-PARP
      antibody. mRNA and miRNA levels were quantified by real-time PCR. RESULTS: All
      tested nutraceuticals caused in both cell lines decrease of cell viability and
      increase of apoptosis. In contrast, only curcumin reduced in vitro aggressiveness
      in both SW1736 and 8505C cell lines, while genistein and EGCG determined a
      reduction of colony formation only in 8505C cells. Effects on genes related to
      the thyroid-differentiated phenotype were also tested: resveratrol and genistein
      administration determined the increment of almost all tested mRNAs in both cell
      lines. Instead curcumin and EGCG treatments had opposite effects in the two cell
      lines, causing the increment of almost all the mRNAs in 8505C cells and their
      reduction in SW1736. Finally, effects of nutraceuticals on levels of several
      miRNAs, known as important in thyroid cancer progression (hsa-miR-221, hsa-miR
      222, hsa-miR-21, hsa-miR-146b, hsa-miR-204), were tested. Curcumin induced a
      strong and significant reduction of all miR analyzed, except for has-miR-204, in
      both cell lines. CONCLUSIONS: Altogether, our results clearly indicate the anti
      cancer proprieties of curcumin, suggesting the promising use of this
      nutraceutical in ATC treatment. Resveratrol, genistein and EGCG have
      heterogeneous effects on molecular features of ATC cells.

PMID- 29197968
TI  - Thulium-yttrium-aluminium-garnet (Tm:YAG) laser treatment of penile cancer:
      oncological results, functional outcomes, and quality of life.
AB  - PURPOSE: To evaluate the oncological and functional outcomes of patients
      diagnosed with penile cancer undergoing conservative treatment through thulium
      yttrium-aluminium-garnet (Tm:YAG) laser ablation. METHODS: Twenty-six patients
      with a penile lesion underwent ablation with a RevoLix 200 W continuous-wave
      laser. The procedure was carried out with a pen-like laser hand piece, using a
      360 MUm laser fiber and 15-20 W of power. Median (IQR) follow-up time was 24 (15
      30) months. Recurrence rate and post-operative sexual function were assessed.
      RESULTS: Median age at surgery was 61 years. Median (inter quartile range) size
      of the lesions was 15 [10-20] mm. Overall, 11 (47.8%) and 12 (52.2%) at the final
      pathology presented in situ and invasive squamous cell carcinoma (SCC),
      respectively. The final pathological stage was pTis, pT1a, pT2, and pT3 in 11
      (47.8%), 7 (30.4%), 3 (13.0%), and 2 (8.7%) patients, respectively. Moreover,
      four (17.4%) patients had a recurrence of which three (13.0%) and one (4.3%)
      patients developed an invasive or in situ recurrence, respectively. After
      treatment 6 (26.1%) patients reported a conserved penile sensitivity, while 13
      (56.5%) and 4 (17.4%) patients experienced a better or worse sensitivity after
      ablation, respectively. Post-treatment sexual activity was achieved within the
      first month after laser ablation in 82.6% of the patients. CONCLUSION: Early
      stage penile carcinomas can be effectively treated with an organ preservation
      strategy. Tm:YAG conservative laser treatment is easy, safe and offers good
      functional outcome, with a minor impact on patient's quality of life.

PMID- 29197969
TI  - The association of early life socioeconomic position on breast cancer incidence
      and mortality: a systematic review.
AB  - OBJECTIVES: We conducted a systematic review of the literature relating early
      life socioeconomic position (SEP) to breast cancer incidence and mortality from a
      critical period and life-course trajectory perspective. METHODS: PubMed, EMBASE
      and Web of Science were searched to identify cohort studies that evaluated the
      impact of early life SEP indicators on the incidence and/or mortality from breast
      cancer in adulthood. RESULTS: Nine distinct studies evaluated the relationship
      between early life SEP and breast cancer between 1990 and 2016. Five reports
      assessed breast cancer incidence and five assessed breast cancer mortality as
      outcomes; one study assessed both incidence and mortality. While lower early life
      SEP was associated with reduced breast cancer incidence and increased breast
      cancer mortality in the US, studies conducted in Europe were unable to establish
      a consistent association. CONCLUSIONS: We found moderate support for the
      association between early life SEP and incidence and mortality from breast
      cancer. The impact of early life SEP on breast cancer incidence and mortality
      appeared to vary between countries. We urge further investigation of the role of
      lifelong SEP trajectories in breast cancer outcomes.

PMID- 29197970
TI  - Distinct renal outcomes for transcatheter aortic valve replacement and surgical
      repair.

PMID- 29197971
TI  - Comparison of long-term follow-up outcomes between multiple-drugs combination
      therapy and tonsillectomy pulse therapy for pediatric IgA nephropathy.
AB  - BACKGROUND: To clarify the long-term efficacy of multiple-drugs combination
      therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA
      nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory
      findings as well as the prognosis for IgAN patients treated with each treatment
      at long-term follow-up. METHODS: We collected data on 61 children who had been
      diagnosed with severe IgAN. The children were retrospectively divided into two
      groups. Group 1 consisted of 44 severe IgAN children treated with PWDM, and Group
      2 consisted of 17 severe IgAN children treated with TPT. The clinical features,
      pathological findings, and prognosis were analyzed for both groups. RESULTS: The
      mean urinary protein excretion, serum creatinine, IgA levels, MESTCG scores, and
      percentage of glomeruli showing crescents in both groups at the second renal
      biopsy were lower than those at the first renal biopsy. At the time of the second
      biopsy, the IgA level in Group 2 was lower than that in Group 1; however, there
      were no significant differences in the mean urinary protein excretion, frequency
      of hematuria, serum albumin, creatinine, or e-GFR between the two groups. At the
      most recent follow-up, there were no significant differences in prognosis between
      the groups. CONCLUSIONS: Our study suggested that PWDM and TPT are effective in
      ameliorating urinary abnormalities and improving the long-term outcome of
      pediatric IgAN.

PMID- 29197972
TI  - Prognostic value of intraoperative measurements of renal tissue oxygenation and
      microcirculation on renal function in partial nephrectomy.
AB  - BACKGROUND: Partial nephrectomy (PNx) can be associated with macrocirculatory and
      microcirculatory alterations, ultimately leading to acute kidney injury (AKI).
      Measuring kidney tissue oxygenation (MUHbO2) and microcirculation during open PNx
      might be feasible to early detect these alterations and prevent postoperative
      AKI. METHODS: MUHbO2 and microcirculation were measured in 45 patients undergoing
      PNx by reflectance spectrophotometry and laser Doppler flowmetry (O2CTM, Lea,
      Germany), related to ischemia time and tumour size. Pre- and postoperative
      creatinine levels were determined. RESULTS: MUHbO2 was lower after reperfusion
      than before clamping (72 vs. 75%), while microcirculation and regional
      haemoglobin did not differ. Ischemia time was 15.7 min on average. MUHbO2 was
      higher without ischemia (80 vs. 70%, p = 0.109) and in T1a- than T1b-tumours,
      independent of ischemia time and reperfusion. The renal collecting system (RCS)
      was opened in 19/45 patients with MUHbO2 of 68% after reperfusion compared to 74%
      with intact RCS. Postoperative complications occurred in 6/45 patients (13%).
      MUHbO2 was 68% before clamping vs. 75% without complications. Serum creatinine of
      patients with T1b was higher compared to T1a (103 vs. 87 umol/L). Patients with
      larger tumours had higher postoperative creatinine levels (173 vs. 124 umol/L; p
      = 0.052). CONCLUSION: We showed for the first time that the method is feasible to
      monitor renal tissue oxygenation at the level of microcirculation non-invasively
      and reproducibly during PNx. Tumour size seems to have a decisive influence on
      oxygenation and postoperative renal function. Our results imply that
      postoperative complications may be predicted by low intraoperative renal
      oxygenation and microcirculatory flow measurements.

PMID- 29197973
TI  - Fire and grazing modulate the structure and resistance of plant-floral visitor
      networks in a tallgrass prairie.
AB  - Significant loss of pollinator taxa and their interactions with flowering plants
      has resulted in growing reductions to pollination services globally. Ecological
      network analysis is a useful tool for evaluating factors that alter the
      interaction structure and resistance of systems to species loss, but is rarely
      applied across multiple empirical networks sampled within the same study. The non
      random arrangement of species interactions within a community, or "network
      structure" such as nested or modular organization, is predicted to prevent
      extinction cascades in ecological networks. How ecological gradients such as
      disturbance regimes shape network structural properties remains poorly understood
      despite significant efforts to quantify interaction structure in natural systems.
      Here, we examine changes in the structure of plant-floral visitor networks in a
      tallgrass prairie using a decadal and landscape-scale experiment that manipulates
      prescribed burn frequency and ungulate grazing, resulting in different grassland
      states. Plant and floral visitor communities and accompanying network structure
      were impacted by grassland fire and grazing regimes. The presence of grazers
      increased flowering plant species richness, network floral visitor species
      richness, and decreased network nestedness. Fire frequency affected flowering
      plant and floral visitor community composition; community composition impacted
      network specialization and modularity. Grassland state resulting from fire
      grazing interactions has important implications for the resistance of flowering
      plant and floral visitor communities to species loss.

PMID- 29197974
TI  - Fitness correlates of age at primiparity in a hunted moose population.
AB  - Trade-offs between fitness-related traits are predicted from the principle of
      resource allocation, where increased fecundity or parental investment leads to
      reduced future reproduction or survival. However, fitness traits can also be
      positively correlated due to individual differences (e.g. body mass). Age at
      primiparity could potentially explain variation in individual fitness either
      because early primiparity is costly, or it may lead to higher lifetime
      reproductive success. Based on long-term monitoring and genetic parentage
      assignment of an island population of moose, we quantified reproductive
      performance and survival, and examined whether early maturing females have higher
      total calf production than late maturing females. We explored if harvesting of
      calves affected the subsequent reproductive success of their mothers, i.e. also
      due to a post-weaning cost of reproduction, and whether there are any
      intergenerational effects of female reproductive success. There was a positive
      relationship between current and future reproduction. The probability to
      reproduce was lower for females that were unsuccessful the year before,
      indicating a strong quality effect on productivity. Females that started to
      reproduce as 2-year olds had a slightly higher total calf production compared to
      those starting at age three or four. High-performing mothers were also correlated
      with daughters that performed well in terms of reproductive success. Our results
      suggest that the observed individual heterogeneity in fitness could be associated
      with differences in age at primiparity. This heterogeneity was not affected by
      reproductive costs associated with tending for a calf post-weaning.

PMID- 29197975
TI  - Selective labeling and unlabeling strategies in protein solid-state NMR
      spectroscopy.
AB  - Selective isotope labeling is central in NMR experiments and often allows to push
      the limits on the systems investigated. It has the advantage to supply additional
      resolution by diminishing the number of signals in the spectra. This is
      particularly interesting when dealing with the large protein systems which are
      currently becoming accessible to solid-state NMR studies. Isotope labeled
      proteins for NMR experiments are most often expressed in E. coli systems, where
      bacteria are grown in minimal media supplemented with 15NH4Cl and 13C-glucose as
      sole source of nitrogen and carbon. For amino acids selective labeling or
      unlabeling, specific amino acids are supplemented in the minimal medium. The aim
      is that they will be incorporated in the protein by the bacteria. However, E.
      coli amino-acid anabolism and catabolism tend to interconnect different pathways,
      remnant of a subway system. These connections lead to inter conversion between
      amino acids, called scrambling. A thorough understanding of the involved pathways
      is thus important to obtain the desired labeling schemes, as not all combinations
      of amino acids are adapted. We present here a detailed overview of amino-acid
      metabolism in this context. Each amino-acid pathway is described in order to
      define accessible combinations for 13C or 15N specific labeling or unlabeling.
      Using as example the ABC transporter BmrA, a membrane protein of 600 residues, we
      demonstrate how these strategies can be applied. Indeed, even though there is no
      size limit in solid-state NMR, large (membrane) proteins are still a challenge
      due to heavy signal overlap. To initiate resonance assignment in these large
      systems, we describe how selectively labeled samples can be obtained with the
      addition of labeled or unlabeled amino acids in the medium. The reduced spectral
      overlap enabled us to identify typical spectral fingerprints and to initiate
      sequential assignment using the more sensitive 2D DARR experiments with long
      mixing time showing inter-residue correlations.

PMID- 29197976
TI  - Genetically encoded amino acids with tert-butyl and trimethylsilyl groups for
      site-selective studies of proteins by NMR spectroscopy.
AB  - The amino acids 4-(tert-butyl)phenylalanine (Tbf) and 4
      (trimethylsilyl)phenylalanine (TMSf), as well as a partially deuterated version
      of Tbf (dTbf), were chemically synthesized and site-specifically incorporated
      into different proteins, using an amber stop codon, suppressor tRNA and the
      broadband aminoacyl-tRNA synthetase originally evolved for the incorporation of p
      cyano-phenylalanine. The 1H-NMR signals of the tert-butyl and TMS groups were
      compared to the 1H-NMR signal of tert-butyltyrosine (Tby) in protein systems with
      molecular weights ranging from 8 to 54 kDa. The 1H-NMR resonance of the TMS group
      appeared near 0 ppm in a spectral region with few protein resonances,
      facilitating the observation of signal changes in response to ligand binding. In
      all proteins, the R 2 relaxation rate of the tert-butyl group of Tbf was only
      little greater than that of Tby (less than two-fold). Deuteration of the phenyl
      ring of Tbf made only a relatively small difference. The effective T 2 relaxation
      time of the TMS signal was longer than 140 ms even in the 54 kDa system.

PMID- 29197977
TI  - Direct assignment of 13C solid-state NMR signals of TFoF1 ATP synthase subunit c
      ring in lipid membranes and its implication for the ring structure.
AB  - FoF1-ATP synthase catalyzes ATP hydrolysis/synthesis coupled with a transmembrane
      H+ translocation in membranes. The Fo c-subunit ring plays a major role in this
      reaction. We have developed an assignment strategy for solid-state 13C NMR
      (ssNMR) signals of the Fo c-subunit ring of thermophilic Bacillus PS3 (TFo c
      ring, 72 residues), carrying one of the basic folds of membrane proteins. In a
      ssNMR spectrum of uniformly 13C-labeled sample, the signal overlap has been a
      major bottleneck because most amino acid residues are hydrophobic. To overcome
      signal overlapping, we developed a method designated as COmplementary Sequential
      assignment with MInimum Labeling Ensemble (COSMILE). According to this method, we
      generated three kinds of reverse-labeled samples to suppress signal overlapping.
      To assign the carbon signals sequentially, two-dimensional Calpha(i+1)
      C'Calpha(i) correlation and dipolar assisted rotational resonance (DARR)
      experiments were performed under magic-angle sample spinning. On the basis of
      inter- and intra-residue 13C-13C chemical shift correlations, 97% of Calpha, 97%
      of Cbeta and 92% of C' signals were assigned directly from the spectra. Secondary
      structure analysis predicted a hairpin fold of two helices with a central loop.
      The effects of saturated and unsaturated phosphatidylcholines on TFo c-ring
      structure were examined. The DARR spectra at 15 ms mixing time are essentially
      similar to each other in saturated and unsaturated lipid membranes, suggesting
      that TFo c-rings have similar structures under the different environments. The
      spectrum of the sample in saturated lipid membranes showed better resolution and
      structural stability in the gel state. The C-terminal helix was suggested to
      locate in the outer layer of the c-ring.

PMID- 29197978
TI  - The Development of Anaphora Resolution at the Syntax-Discourse Interface:
      Pronominal Subjects in Greek Learners of Spanish.
AB  - This study explores the development of anaphora resolution (AR) in late
      sequential bilinguals, namely, adult Greek learners of Spanish at three
      proficiency levels (intermediate, lower advanced, upper advanced). The use of an
      overt/null pronominal subject anaphor is investigated in three discourse
      contexts: topic-continuity (a single antecedent requiring a null pronoun),
      contrastive-focus (two same-gender potential antecedents requiring an overt
      pronoun to avoid ambiguity) and emphatic (three same-gender potential antecedents
      showing unclear preference for either overt or null pronoun). Crucially, AR
      behaves similarly in Greek and Spanish. Results from an offline contextualised
      acceptability judgement task show that similarity between the learner's first
      (L1) and second (L2) languages does not necessarily facilitate the learning task.
      Even very advanced learners show deficits, which are selective since not all
      discursive contexts are equally affected. The results are better accounted for by
      general pragmatic economy principles: Learners prefer being redundant (overuse of
      overt pronouns in topic-continuity contexts) to ambiguous (acceptance of null
      pronouns in contrastive-focus contexts). Such tolerance for redundancy may
      reflect a more general pragmatic tendency, as also reported in child L1
      development, adult L2 development and also in native grammars.

PMID- 29197980
TI  - Correction to: Iron and infection.
AB  - The author would like to correct the error in the "Abstract" section of original
      publication as given below.

PMID- 29197979
TI  - Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect
      sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance
      to studies of human neurological disorders.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a
      human health concern with newly discovered sources of contamination and ongoing
      bioaccumulation and biomagnification. Children exposed during early brain
      development are at highest risk of neurological deficits, but highly exposed
      adults reportedly have an increased risk of Parkinson's disease. Our previous
      studies found allelic differences in the aryl hydrocarbon receptor and cytochrome
      P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in
      cognitive deficits and motor dysfunction. High-affinity Ahr b Cyp1a2(-/-) mice
      were most sensitive compared with poor-affinity Ahr d Cyp1a2(-/-) and wild-type
      Ahr b Cyp1a2(+/+) mice. Our follow-up studies assessed biochemical, histological,
      and gene expression changes to identify the brain regions and pathways affected.
      We also measured PCB and metabolite levels in tissues to determine if genotype
      altered toxicokinetics. We found evidence of AHR-mediated toxicity with reduced
      thymus and spleen weights and significantly reduced thyroxine at P14 in PCB
      exposed pups. In the brain, the greatest changes were seen in the cerebellum
      where a foliation defect was over-represented in Cyp1a2(-/-) mice. In contrast,
      we found no difference in tyrosine hydroxylase immunostaining in the striatum.
      Gene expression patterns varied across the three genotypes, but there was clear
      evidence of AHR activation. Distribution of parent PCB congeners also varied by
      genotype with strikingly high levels of PCB 77 in poor-affinity Ahr d Cyp1a2(-/-)
      while Ahr b Cyp1a2(+/+) mice effectively sequestered coplanar PCBs in the liver.
      Together, our data suggest that the AHR pathway plays a role in developmental PCB
      neurotoxicity, but we found little evidence that developmental exposure is a risk
      factor for Parkinson's disease.

PMID- 29197981
TI  - The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male
      and female rats: estrous cycle effects on behavior and protein expression in the
      nucleus accumbens.
AB  - RATIONALE: Effective pharmacological treatments to prevent cocaine relapse remain
      elusive. In male rats, ceftriaxone attenuates the reinstatement of cocaine
      seeking while increasing glutamate transporter-1 (GLT-1) and xCT expression in
      the nucleus accumbens core (NAc). Despite reported sex differences in cocaine
      relapse, these effects have not yet been confirmed in female rats. OBJECTIVE: We
      investigated the effects of ceftriaxone on cue-primed reinstatement and cocaine
      induced alterations in glutamatergic proteins in the NAc of female rats.
      Potential interactions between estrous phase and treatment were also assessed.
      METHOD: Male and female rats self-administered cocaine in the presence of
      discrete cues for 12 days, followed by 2-3 weeks of extinction. Ceftriaxone or
      vehicle was administered daily for a minimum of 6 days immediately preceding a
      cue-primed reinstatement test. RESULTS: Total cocaine intake was greater in
      females than in males, but reinstatement behavior was similar. Ceftriaxone
      attenuated reinstatement in both sexes and was accompanied by increased
      expression of GLT-1a and xCT in the NAc. However, ceftriaxone attenuated
      reinstatement only when females were tested during met-, di-, and proestrus
      phases and not during estrus. A significant increase in AMPA receptor subunit
      GluA1 surface expression was also observed during estrus, potentially influencing
      reinstatement. CONCLUSION: These findings extend the beneficial effects of
      ceftriaxone on persistent cocaine-seeking from males to females, increasing its
      potential as a pharmacological treatment for preventing relapse. The effects of
      estrus on GluA1 expression and reinstatement observed here indicate that females
      may need additional interventions during some phases of the menstrual cycle.

PMID- 29197982
TI  - Dissociation of place preference and tolerance responses to sucrose using a
      dopamine antagonist in the planarian.
AB  - In rodents, sucrose has been found to elicit addictive-like behaviours like the
      development of tolerance and the association with cues present at the time of
      consumption. Furthermore, the neurochemical response to sucrose binges is
      equivalent to the one observed in response to the abuse of addictive substances
      like cocaine. The experiments reported here address the effects of sucrose on an
      invertebrate model, the Platyhelminth brown planarian. The animals exposed to a
      10% sucrose solution in one context developed a conditioned place preference
      (CPP) which was subsequently extinguished in the absence of the rewarding agent.
      However, one exposure to sucrose per se sufficed to reinstate the CPP response,
      suggesting sucrose-induced CPP can be characterised as a standard Pavlovian
      response. The same training procedure led to the development of context-specific
      tolerance to the effects of sucrose. However, comparing animals treated with
      dopamine D1 antagonist (SCH-23390) with control animals showed that the
      establishment of CPP, but not the development of tolerance, is mediated by the
      dopamine reward system.

PMID- 29197983
TI  - Reduced sensitivity to reinforcement in adolescent compared to adult Sprague
      Dawley rats of both sexes.
AB  - RATIONALE: Adolescence is a period of considerable development of brain and
      behavior and is the time during which most drug use is initiated. OBJECTIVE: Age
      dependent differences in motivated behaviors may be one of the factors that
      contribute to heightened vulnerability to developing substance use disorders, so
      we sought to compare age differences in methamphetamine (METH) and saccharin
      seeking. METHODS: Beginning during adolescence or adulthood, male and female
      Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid
      dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08
      mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently,
      responding for METH (0.02, 0.05, 0.08, or 0.1 mg/kg/inf) under progressive ratio
      response requirements was assessed in rats that acquired METH self-administration
      at the highest dose (0.08 mg/kg/inf). RESULTS: We found that adult-onset rats
      acquired METH self-administration more readily and exhibited higher motivation
      compared to adolescent-onset rats, although there were no differences in METH
      intake during acquisition. Adult rats also acquired saccharin self-administration
      more readily, but in contrast to METH, there were age and sex differences in
      saccharin intake driven by high levels of responding in adult females.
      CONCLUSIONS: These findings challenge the prevailing notion that adolescents are
      hypersensitive to reward and instead raise questions about the potential role of
      methodological factors on which rodent studies often differ.

PMID- 29197984
TI  - Altered orbitofrontal activity and dorsal striatal connectivity during emotion
      processing in dependent marijuana users after 28 days of abstinence.
AB  - RATIONALE: Intact cognitive and emotional functioning is vital for the long-term
      success of addiction treatment strategies. Accumulating evidence suggests an
      association between chronic marijuana use and lasting alterations in cognitive
      brain function. Despite initial evidence for altered emotion processing in
      dependent marijuana users after short abstinence periods, adaptations in the
      domain of emotion processing after longer abstinence remain to be determined.
      OBJECTIVE AND METHODS: Using task-based and resting state fMRI, the present study
      investigated emotion processing in 19 dependent marijuana users and 18 matched
      non-using controls after an abstinence period of > 28 days. RESULTS: Relative to
      the control subjects, negative emotional stimuli elicited increased medial
      orbitofrontal cortex (mOFC) activity and stronger mOFC-dorsal striatal and mOFC
      amygdala functional coupling in dependent marijuana users (p < 0.022, FWE
      corrected). Furthermore, mOFC-dorsal striatal functional connectivity was
      increased at rest in marijuana users (p < 0.03, FWE-corrected). Yet, processing
      of positive stimuli and subjective ratings of valence and arousal were comparable
      in both groups. CONCLUSIONS: Together, the present findings provide the first
      evidence for persisting emotion processing alterations in dependent marijuana
      users. Alterations might reflect long-term neural adaptations as a consequence of
      chronic marijuana use or predisposing risk factors for the development of
      marijuana dependence.

PMID- 29197985
TI  - Pervasive interactions of Sa and Sb loci cause high pollen sterility and abrupt
      changes in gene expression during meiosis that could be overcome by double
      neutral genes in autotetraploid rice.
AB  - BACKGROUND: Intersubspecific autotetraploid rice hybrids possess high hybrid
      vigor; however, low pollen fertility is a critical hindrance in its commercial
      utilization. Our previous study demonstrated that polyploidy could increase the
      multi-loci interaction and cause high pollen abortion in autotetraploid rice
      hybrids. However, there is little known about the critical role of pollen
      sterility locus or loci in the intersubspecific hybrids. We developed
      autotetraploid rice hybrids harboring heterozygous genotypes (S i S i S j S j )
      at different pollen sterility loci by using the near isogenic lines of Taichung65
      4*. Moreover, autotetraploid lines carrying double neutral genes, Sa n and Sb n ,
      were used to assess their effect on fertility restoration. RESULTS: Cytological
      studies showed that the deleterious genetic interactions at Sa and Sb pollen
      sterility loci resulted in higher pollen sterility (76.83%) and abnormal
      chromosome behavior (24.59%) at metaphase I of meiosis in autotetraploid rice
      hybrids. Transcriptome analysis revealed 1092 differentially expressed genes
      (DEG) in a hybrid with the pervasive interactions at Sa and Sb pollen sterility
      loci, and most of the genes (about 83%) exhibited down regulation. Of the DEG, 60
      were associated with transcription regulation and 18 genes were annotated as
      meiosis-related genes. Analysis on the hybrids developed by using autotetraploid
      rice harboring double neutral genes, Sa n and Sb n , revealed normal pollen
      fertility, and transcriptome analysis showed non-significant difference in number
      of DEG among different hybrids. CONCLUSIONS: Our finding revealed that pervasive
      interactions at Sa and Sb pollen sterility loci cause high sterility in the
      autotetraploid hybrids that lead to the down-regulation of important meiosis
      related genes and transcription regulation factors. Moreover, we also found that
      the hybrids sterility could be overcome by double neutral genes, Sa n and Sb n ,
      in autotetraploid rice hybrids. The present study provided a strong evidence for
      the utilization of heterosis in autotetraploid rice hybrids.

PMID- 29197987
TI  - Surgery in adenomyosis.
AB  - INTRODUCTION: Adenomyosis is defined as the presence of endometrial glands and
      stroma within the myometrium. The true prevalence is unknown and has been
      reported to range from 1 to 70%. It has a significantly negative impact on
      women's quality of life, causing abnormal uterine bleeding, dysmenorrhea, and
      chronic pelvic pain. The definitive treatment for adenomyosis is hysterectomy,
      although it does not contemplate patients who wish to preserve their fertility.
      The aim of this paper is to discuss the latest evidence on the surgical
      techniques for the treatment of adenomyosis published in medical-scientific
      databases. METHOD: A comprehensive literature search for articles published from
      1996 to 2017 related to surgery for adenomyosis was made in Pubmed, Medline, the
      Cochrane Library, and Google Scholar, in English, by the following MeSH terms:
      adenomyosis, surgery, pathogenesis, dysmenorrhea and infertility. RESULTS: There
      is extensive evidence on several surgical approaches for the improvement of
      adenomyosis-related symptoms; however, there is no robust evidence that they are
      effective for infertility. CONCLUSION: The management of adenomyosis is quite
      complex and controversial. Complications after extensive uterine reconstruction,
      such as uterine rupture, should be considered and discussed with the patient.
      There are still limited data to support surgery effectiveness, especially for
      infertility, and further well-designed studies are required.

PMID- 29197986
TI  - Relationships between MRI fat distributions and sleep apnea and obesity
      hypoventilation syndrome in very obese patients.
AB  - PURPOSE: Obesity is associated with both obstructive sleep apnea (OSA) and
      obesity hypoventilation. Differences in adipose tissue distribution are thought
      to underlie the development of both OSA and hypoventilation. We explored the
      relationships between the distribution of upper airway, neck, chest, abdominal
      and muscle fat in very obese individuals. METHODS: We conducted a cross-sectional
      cohort study of individuals presenting to a tertiary sleep clinic or for
      assessment for bariatric surgery. Individuals underwent magnetic resonance (MR)
      imaging of their upper airway, neck, chest, abdomen and thighs; respiratory
      polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to
      determine carbon dioxide partial pressure and base excess. RESULTS: Fifty-three
      individuals were included, with mean age of 51.6 +/- 8.4 years and mean BMI of
      44.3 +/- 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral
      wall volumes were significantly associated with the AHI in univariable analyses
      (p < 0.001). Gender was a significant confounder in these associations. No
      significant associations were found between MRI measures of adiposity and
      hypoventilation. CONCLUSIONS: In very obese individuals, our results indicate
      that increased volumes of upper airway structures are associated with increased
      severity of OSA, as previously reported in less obese individuals. Increasingly
      large upper airway structures that reduce pharyngeal lumen size are likely to
      lead to OSA by increasing the collapsibility of the upper airway. However, we did
      not show any significant association between regional fat distribution and
      propensity for hypoventilation, in this population.

PMID- 29197988
TI  - Impact of circulating bacterial DNA in long-term glucose homeostasis in non
      diabetic patients with HIV infection: cohort study.
AB  - In HIV-infected patients, the damage in the gut mucosal immune system is not
      completely restored after antiretroviral therapy (ART). It results in microbial
      translocation, which could influence the immune and inflammatory response. We
      aimed at investigating the long-term impact of bacterial-DNA translocation
      (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in
      HIV-infected patients whereby inclusion criteria were: patients with age >18
      years, ART-naive or on effective ART (<50 HIV-1 RNA copies/mL) and without
      diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%).
      Explanatory variables at baseline were: bactDNA (qualitatively detected in blood
      samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure,
      HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model
      assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral
      fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 +/-
      8.3 years, BMI 24.9 +/- 3 kg/m2, mean duration of HIV infection of 8.1 +/- 5.3
      years) were included. Baseline HbA1c was 4.4 +/- 0.4% and baseline presence of
      BactDNA in six patients. After 8.5 +/- 0.5 years of follow-up, change in HbA1c
      was 1.5 +/- 0.47% in patients with BactDNA vs 0.87 +/- 0.3% in the rest of the
      sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors
      exposure, but not by baseline indices of insulin resistance, body composition,
      hepatic steatosis, inflammatory markers or anthropometric changes. In non
      diabetic patients with HIV infection, baseline bacterial translocation and PI
      exposure time were the only factors associated with long-term impaired glucose
      homeostasis.

PMID- 29197989
TI  - Direct genetic characterization of Toxoplasma gondii from clinical samples from
      Denmark: not only genotypes II and III.
AB  - Genetic variation within Toxoplasma gondii can have both clinical and
      epidemiological significance, while the genotypes circulating in many parts of
      the world, including the Nordic country Denmark, are still unknown. We
      genetically characterized T. gondii strains that had been detected in human
      clinical samples in Denmark in 2011-2016. Samples that had tested positive for T.
      gondii DNA and had a quantification cycle value <33 were included in this study
      and subjected to direct genetic characterization of T. gondii based on length
      polymorphism of 15 microsatellite markers. A total of 23 DNA samples from 22
      individual patients were analyzed. The results were consistent with genotype II
      with 15/15 markers amplified from seven samples from the central nervous system
      (CNS) including two samples from one patient, four ocular samples, and one
      unspecified sample; with genotype III with 15/15 markers amplified from two
      ocular samples; with genotype Africa 1 with 15/15 markers amplified from one
      amniotic fluid sample and from one CNS-sample; with atypical genotype with 15/15
      markers amplified from one CNS-sample and with 11/15 markers amplified from one
      CNS-sample; and with HG12-like genotype with 9/15 markers amplified from one CNS
      sample. Genotype II, which is endemic in Europe, was predominant, but more than a
      third of the successfully genotyped strains were non-type-II. The possibility
      that clinical toxoplasmosis is caused by a strain that is not considered endemic
      to the region is definitely not negligible.

PMID- 29197990
TI  - Modeling mechanical inhomogeneities in small populations of proliferating
      monolayers and spheroids.
AB  - Understanding the mechanical behavior of multicellular monolayers and spheroids
      is fundamental to tissue culture, organism development, and the early stages of
      tumor growth. Proliferating cells in monolayers and spheroids experience
      mechanical forces as they grow and divide and local inhomogeneities in the
      mechanical microenvironment can cause individual cells within the multicellular
      system to grow and divide at different rates. This differential growth, combined
      with cell division and reorganization, leads to residual stress. Multiple
      different modeling approaches have been taken to understand and predict the
      residual stresses that arise in growing multicellular systems, particularly tumor
      spheroids. Here, we show that by using a mechanically robust agent-based model
      constructed with the peridynamic framework, we gain a better understanding of
      residual stresses in multicellular systems as they grow from a single cell. In
      particular, we focus on small populations of cells (1-100 s) where population
      behavior is highly stochastic and prior investigation has been limited. We
      compare the average strain energy density of cells in monolayers and spheroids
      using different growth and division rules and find that, on average, cells in
      spheroids have a higher strain energy density than cells in monolayers. We also
      find that cells in the interior of a growing spheroid are, on average, in
      compression. Finally, we demonstrate the importance of accounting for stochastic
      fluctuations in the mechanical environment, particularly when the cellular
      response to mechanical cues is nonlinear. The results presented here serve as a
      starting point for both further investigation with agent-based models, and for
      the incorporation of major findings from agent-based models into continuum scale
      models when explicit representation of individual cells is not computationally
      feasible.

PMID- 29197991
TI  - Experimental determination of folding factor of benign breast cancer cell
      (MCF10A) and its effect on contact models and 3D manipulation of biological
      particles.
AB  - Plasma membrane of most cells is not smooth. The surfaces of both small and large
      micropermeable cells are folded and corrugated which makes mammalian cells to
      have a larger membrane surface than the supposed ideal mode, that is, the smooth
      sphere of the same volume. Since cancer is an anthropic disease, cancer cells
      tend to have a larger membrane area than normal cells. Therefore, cancer cells
      have higher folding factor and larger radius than normal and healthy cells. On
      the other hand, the prevalence of breast cancer has prompted researchers to
      improve the treatment options raised for the disease in the past. In this paper,
      the impact of folding factor of the cell surface has been investigated.
      Considering that AFM is one of the most effective tools in performing the tests
      at micro- and nanoscales, it was used to determine the topography of MCF10 cells
      and then the resulting images and results were used to experimentally extract the
      folding factor of cells. By applying this factor in the Hertz, DMT and JKR
      contact models in the elastic and viscoelastic states, these models have been
      modified and the simulation of the three models shows that the simulation results
      are closer to the experimental results by considering the folding in the
      calculations. Additionally, the simulation of 3D manipulation has been done in
      both elastic and viscoelastic states with and without consideration of folding.
      Finally, the results were compared to investigate the effects of folding of the
      cell surface to the critical force and critical time of sliding and rolling in
      contact with the substrate and AFM tip in the 3D manipulation model.

PMID- 29197992
TI  - Identification of Reference Genes for Analysis of microRNA Expression Patterns in
      Equine Chorioallantoic Membrane and Serum.
AB  - MicroRNAs (miRNAs) have important posttranscriptional regulatory abilities, and
      there is considerable interest in evaluating their expression patterns in
      different pathophysiological states. The most common method of quantifying miRNA
      expression is quantitative reverse transcription PCR; however, the identification
      of tissue-specific and species-specific reference miRNA is a prerequisite for
      miRNA expression analysis. Currently, no reference genes have been described for
      evaluating miRNA expression in equine serum and chorioallantoic membrane (CAM)
      during pregnancy. The aim of the present study was to characterize reference
      genes for normalization of miRNA expression in CAM and serum in the pregnant
      equine. To identify the most stable miRNAs in serum, expression of potential
      candidates was evaluated in serum samples from diestrous mares, pregnant mares
      and geldings. To identify the most stable miRNAs in CAM, expression of potential
      candidates was evaluated in CAM, collected from mares at 4, 6 and 10 months of
      pregnancy and immediately postpartum. From a previously generated miRNA
      sequencing dataset, two separate lists of potential reference miRNAs were
      identified (serum and CAM) using the NormFinder program, in addition to the
      commonly used small RNA normalizers, 5S rRNA and U6 snRNA. The putative reference
      miRNAs were selected using geNorm and NormFinder. In case of a nonsignificant
      correlation between the results of ranking and stability value between these two
      programs, ranking from BestKeeper was also included. NormFinder and geNorm
      consistently identified eca-miR-21-5p, eca-let-7a-5p and eca-miR-10a-5p as the
      three most stable reference genes for the normalization of serum miRNAs. Within
      CAM samples, the average ranking obtained from the ranking of NormFinder, geNorm
      and BestKeeper identified eca-miR-8908a-1-5p, eca-miR-369-5p and eca-miR-106a-5p
      as the three most stable miRNAs. These observations provide information about
      equine-specific reference genes that can be used for normalizing miRNAs
      expression patterns in CAM and serum during the equine pregnancy.

PMID- 29197993
TI  - Chloramine T induced oxidative stress and the response of antioxidant system in
      Phanerochaete chrysosporium.
AB  - In this study, the effect of chloramine T (Chl-T) on the activities of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione
      reductase (GR) and glutathione S-transferase (GST); the levels of reduced (GSH)
      and oxidised glutathione (GSSG) and their ratios; and also membrane lipid
      peroxidation (LPO) levels in Phanerochaete chrysosporium were investigated in a
      dose- (0.25-1 mmol/L) and time-dependent (1.5-9 h) manner. The highest SOD
      activity was observed in 0.5 mmol/L Chl-T at 6th hour as 1.48-fold of its
      control. The observed highest level in CAT activities was 4.6-fold of control in
      0.5 and 0.75 mmol/L at the 6th hour. The GSH levels that were over the control
      showed decreasing tendency from the beginning of incubation, except 0.25 mmol/L.
      In contrast with GSH level variations, GSSG levels reached 10.0-fold of its
      control by showing increasing tendency with the increases in concentration and
      time. While the GSH/GSSG ratios were over the control at 0.25 mmol/L during all
      incubation, they fell under the control values at the earlier hours of incubation
      with the increasing concentrations of Chl-T. Glutathione-related enzymes GSH-Px,
      GR and GST were also induced with Chl-T treatment, and the highest activities
      were 3.29-, 7.5- and 6.56-fold of their controls, respectively. On the other
      hand, the increases in LPO levels with increasing concentration and time up to
      5.27-fold of its control showed that the inductions observed in antioxidant
      system could not prevent the Chl-T-based oxidative stress.

PMID- 29197994
TI  - Serum lipids and risk of obesity-related cancers in postmenopausal women.
AB  - PURPOSE: Obesity, which is commonly accompanied by dyslipidemia, is associated
      with an increased risk of certain cancers. However, the association of serum
      lipids with specific obesity-related cancers is unclear. METHODS: We examined the
      association of baseline lipids (total cholesterol, low-density lipoprotein
      cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and
      triglycerides) with risk of developing seven obesity-related cancers in a
      subcohort of 24,208 participants in the Women's Health Initiative. We used Cox
      proportional hazards models to estimate hazard ratios (HRs) and 95% confidence
      intervals (CIs) for quartiles of lipids with cancers of the breast, colorectum,
      pancreas, endometrium, ovary, and kidney, and multiple myeloma. RESULTS: Total
      cholesterol and LDL-C showed no association with these outcomes. HDL-C was
      inversely associated, and triglycerides were positively associated, with several
      cancers. However, after adjustment for other lipids or insulin, consideration of
      preclinical disease, and exclusion of women taking statins, most associations
      were attenuated and no longer significant. Only the inverse association of HDL-C
      with pancreatic cancer (HR for highest vs. lowest quartile 0.52, 95% CI 0.32
      0.85, p for trend 0.007) and the positive association of triglycerides with
      kidney cancer (HR for highest vs. lowest quartile 3.21, 95% CI 1.63-6.33, p for
      trend = 0.0001) remained significant. However, the inverse association of HDL-C
      with pancreatic cancer was no longer significant when women who lost substantial
      weight before diagnosis were excluded. CONCLUSIONS: Our results suggest that when
      possible sources of confounding and bias are taken into account there are few
      robust associations of lipids with obesity-related cancers.

PMID- 29197995
TI  - Long-term patterns of fasting blood glucose levels and pancreatic cancer
      incidence.
AB  - BACKGROUND: Whether type 2 diabetes is cause or consequence, or both, of
      pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of
      fasting blood glucose (FBG), we examined the temporal relationship between
      hyperglycemia and PaC incidence. METHODS: We conducted a nested case-control
      study of 278 cases and 826 matched-controls from the Korean National Health
      Insurance Service-Health Screening Cohort. Over 11 years before index date (date
      of PaC diagnosis for cases), all participants had at least one FBG measurement in
      each of the three time windows: - 11 to - 8, - 7 to - 4, and - 3 to 0 years.
      Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and
      95% confidence intervals (CIs) for hyperglycemia in the overall period and at
      each interval; for major long-term patterns of FBG across the three intervals
      (recent-onset, medium-term, and long-standing hyperglycemia). RESULTS: Higher FBG
      over the past 11 years was associated with an increased odds of PaC (p trend <
      .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed
      in the - 3 to 0 interval, OR was 1.97 (95% CI 1.32-2.93) for 110-125 mg/dL and
      3.17 (95% CI 2.09-4.80) for >= 126 mg/dL. By long-term patterns of FBG, compared
      to consistent normoglycemia, OR was 2.02 (95% CI 1.24-3.31) for long-standing
      hyperglycemia and 3.38 (95% CI 1.87-6.13) for recent-onset hyperglycemia. These
      associations were more pronounced among never-smokers than ever-smokers (p
      interaction = .06). CONCLUSION: Recent-onset hyperglycemia may be an early
      manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a
      moderate etiologic factor for PaC.

PMID- 29197996
TI  - Identification of autofluorescent cells in human angioimmunoblastic T-cell
      lymphoma.
AB  - Endogenous cell autofluorescence is a common nuisance that complicates the use of
      fluorescence microscopy. When using fluorescence-labeled antibodies for specific
      cell labeling in tissue sections of human angioimmunoblastic T-cell lymphoma
      (AITL), we encountered with a problematic autofluorescence of multiple cells.
      These cells emitted fluorescence signals in the green, red and deep-red spectral
      range. Characterization of these autofluorescent cells solely on the basis of
      their autofluorescence failed. To identify these enigmatic cells residing the
      lymphoma tissue, we combined two imaging techniques-fluorescence and brightfield
      microscopy. Combined fluorescence/brightfield imaging of cells immunolabeled with
      a panel of CD antibodies raised against diverse cellular components allowed us to
      identify the autofluorescent cells in the AITL as eosinophils. These cells tended
      to accumulate in the vicinity of capillaries and arterioles apparently mediating
      the process of angiogenesis resembling other angiogenesis-associated diseases.

PMID- 29197997
TI  - Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition
      of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation.
AB  - AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i)
      constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We
      recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic
      Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of
      Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin
      (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a
      structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i
      affect the haemodynamic and metabolic performance of isolated hearts of healthy
      mice. METHODS: Cardiac NHE activity and [Na+]c in mouse cardiomyocytes were
      measured in the presence of clinically relevant concentrations of EMPA (1
      MUmol/l), DAPA (1 MUmol/l), CANA (3 MUmol/l) or vehicle. NHE docking simulation
      studies were applied to explore potential binding sites for SGTL2i. Constant-flow
      Langendorff-perfused mouse hearts were subjected to SGLT2i for 30 min, and
      cardiovascular function, O2 consumption and energetics (phosphocreatine
      (PCr)/ATP) were determined. RESULTS: EMPA, DAPA and CANA inhibited NHE activity
      (measured through low pH recovery after NH4+ pulse: EMPA 6.69 +/- 0.09, DAPA 6.77
      +/- 0.12 and CANA 6.80 +/- 0.18 vs vehicle 7.09 +/- 0.09; p < 0.001 for all three
      comparisons) and reduced [Na+]c (in mmol/l: EMPA 10.0 +/- 0.5, DAPA 10.7 +/- 0.7
      and CANA 11.0 +/- 0.9 vs vehicle 12.7 +/- 0.7; p < 0.001). Docking studies
      provided high binding affinity of all three SGLT2i with the extracellular Na+
      binding site of NHE. EMPA and CANA, but not DAPA, induced coronary vasodilation
      of the intact heart. PCr/ATP remained unaffected. CONCLUSIONS/INTERPRETATION:
      EMPA, DAPA and CANA directly inhibit cardiac NHE flux and reduce [Na+]c, possibly
      by binding with the Na+-binding site of NHE-1. Furthermore, EMPA and CANA affect
      the healthy heart by inducing vasodilation. The [Na+]c-lowering class effect of
      SGLT2i is a potential approach to combat elevated [Na+]c that is known to occur
      in heart failure and diabetes.

PMID- 29197998
TI  - Multisensory enhancement elicited by unconscious visual stimuli.
AB  - The merging of information from different senses (i.e., multisensory integration)
      can facilitate information processing. Processing enhancements have been observed
      with signals that are irrelevant to the task at hand, and with cues that are non
      predictive. Such findings are consistent with the notion that multiple sensory
      signals are sometimes integrated automatically. Multisensory enhancement has even
      been reported with stimuli that have been presented subliminally, though only
      with meaningful multisensory relations that have already been learned. The
      question of whether there exist cases where multisensory effects occur without
      either learning or awareness has, though, not been clearly established in the
      literature to date. Here, we present a case study of a patient with Posterior
      Cortical Atrophy, who was unable to consciously perceive visual stimuli with our
      task parameters, yet who nevertheless still exhibited signs of multisensory
      enhancement even with unlearned relations between audiovisual stimuli. In a
      simple speeded detection task, both response speed, and the variability of
      reaction times, decreased in a similar manner to controls for multisensory
      stimuli. These results are consistent with the view that the conscious perception
      of stimuli and prior learning are not always a prerequisite for multisensory
      integration to enhance human performance.

PMID- 29198000
TI  - Structure-dependent optoelectronic properties of perylene, di-indenoperylene
      (DIP) isolated molecule and DIP molecular crystal.
AB  - Theoretical simulations were designed by first principles approach of density
      functional theory to investigate the structural and optoelectronic properties of
      different structural classes of perylene; isolated perylene, diindeno[1,2,3
      cd:1',2',3'-lm]perylene (DIP) molecule and DIP molecular crystal. The presence of
      molecular interactions in DIP crystal proved its structure-dependent behaviours.
      The herringbone molecular arrangement of DIP crystal has influenced the
      electronic properties by triggering the intermolecular interactions that reduced
      the energy gaps between HOMO and LUMO of the crystal. Strong hybridization
      resulting from dense charges population near zero Fermi energy has pushed valence
      band maxima in the density of states of all perylene structures to higher
      energies. Under small energy input, charges are transferred continuously as
      observed in the spectra of conductivity and dielectric. The existence of strong
      absorption intensities are consistent with the former works and supported by the
      obtained polarized reflectivity and loss spectra.

PMID- 29197999
TI  - Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in
      children with congenital heart disease undergoing cardiopulmonary bypass.
AB  - BACKGROUND: Acute kidney injury (AKI) is one of the most common emergencies and
      severe diseases in the clinic. We sought to verify whether remote ischemic
      preconditioning (RIPC) has a protective effect on the kidney of child with
      congenital heart disease undergoing cardiopulmonary bypass (CPB) surgery. We
      hypothesized it may be related to the up-regulation of microRNA-21 (miR-21).
      METHODS: We performed a prospective randomized clinical study among children with
      congenital heart disease undergoing CPB surgery between January and December
      2016. Children were randomized to an RIPC or control group. Patients in each
      group were divided into an AKI and a non-AKI group according to the occurrence of
      AKI at 48 h after surgery. Remote ischemic preconditioning (RIPC) conducted by
      blood-pressure cuff was performed 12 h before surgery. Serum creatinine (SCr),
      tumor necrosis factor-alpha (TNF-alpha), and miR-21 expression in blood and urine
      were measured at different time points. RESULTS: A total of 449 cases (200 RIPC;
      249 controls) were enrolled. The male/female ratio was 1.18, with a mean age of
      37.50 +/- 25.31 months. The incidence of AKI in the RIPC group was significantly
      lower than that in the control group (19.0% vs. 46.2%, P<0.01). In further
      analysis, at 6 h, 24 h, and 48 h after CPB operation, blood TNF-alpha levels were
      significantly lower in the RIPC group than in the control group (P<0.01); at 24
      h, 48 h, and 72 h, urine TNF-alpha levels were significantly lower in the RIPC
      group than in the control group (P<0.05). Urine and blood miR-21 expression in
      the RIPC group increased significantly, while there was no obvious change in the
      control group. CONCLUSIONS: Remote ischemic preconditioning has a protective
      effect on the kidney in children with congenital heart disease, which may be
      related with the up-regulation of miR-21 and down-regulating the inflammatory
      mediator, such as TNF-alpha.

PMID- 29198001
TI  - Imaging findings of recurrent pancreatic cancer following resection.
AB  - Pancreatic cancer is a challenging malignancy to treat, largely due to aggressive
      regional involvement, early systemic dissemination, high recurrence rate, and
      subsequent low patient survival. Generally, 15-20% of newly diagnosed pancreatic
      cancers are candidates for possible curative resection. Eighty percent of these
      patients, however, will experience locoregional or distant recurrence in first 2
      years. Although there is no strong evidence-based guideline for optimal
      surveillance after pancreatic cancer resection, careful comparison of
      surveillance follow-up multi-detector CT (MDCT) studies with a postoperative
      baseline MDCT examination aids detection of early recurrent pancreatic cancer. In
      this review article, we describe imaging findings suggestive of recurrent
      pancreatic cancer and review routine and alternative imaging options.

PMID- 29198002
TI  - Staging of pancreatic cancer: resectable, borderline resectable, and unresectable
      disease.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a relatively common malignancy that
      carries an overall poor prognosis, with five-year survival below 10%. Despite
      ongoing research, surgical resection remains the only potentially curative
      treatment. Therefore, accurate identification of those patients who would benefit
      from surgical resection is of paramount importance. High-quality imaging and
      image interpretation is central to this process. Radiology helps in the
      determination of whether patients are resectable, borderline resectable, or
      unresectable and guides treatment planning.

PMID- 29198004
TI  - 'Stone street' ureter.
AB  - We would like to submit an interesting image of ureteric steinstrasse post
      lithotripsy procedure resembling a cobble stone street.

PMID- 29198003
TI  - Liver fibrosis detection and staging: a comparative study of T1rho MR imaging and
      2D real-time shear-wave elastography.
AB  - PURPOSE: To compare the results of T1rho MR imaging and 2D real-time shear-wave
      elastography (SWE) for liver fibrosis detection and staging. METHODS: Twenty-nine
      rabbit models of CCl4-induced liver fibrosis were established and six untreated
      rabbits served as controls. T1rho MR imaging and 2D real-time SWE examination
      were performed at 2, 4, 6, 8, 10, and 12 weeks. T1rho values and liver stiffness
      (LS) values were measured. Fibrosis was staged according to the METAVIR scoring
      system. Correlation test was performed among T1rho values, LS values, and
      fibrosis stage. Receiver operating characteristic (ROC) analysis was performed
      for assessing diagnostic performance of T1rho and SWE in detection of no fibrosis
      (F0), substantial fibrosis (>= F2), severe fibrosis (>= F3), and cirrhosis (F4).
      RESULTS: There was moderate positive correlation between fibrosis stage and T1rho
      values (r = 0.566; 95% CI 0.291-0.754; P < 0.0001), and LS value (r = 0.726; 95%
      CI 0.521-0.851; P = 0.003). T1rho values showed moderate positive correlations
      with LS values [r = 0.693; 95% confidence interval (CI) 0.472-0.832; P < 0.0001].
      Areas Under ROC (AUROCs) were 0.861 (95% CI 0.705-0.953) for SWE and 0.856 (95%
      CI 0.698-0.950) for T1rho (P = 0.940), 0.906 (95% CI 0.762-0.978) for SWE and
      0.849 (95% CI 0.691-0.946) for T1rho (P = 0.414), 0.870 (95% CI 0.716-0.958) for
      SWE and 0.799 (95% CI 0.632-0.913) for T1rho (P = 0.422), and 0.846 (95% CI 0.687
      0.944) for SWE and 0.692 (95% CI 0.517-0.835) for T1rho (P = 0.137), when
      diagnosing liver fibrosis with >= F1, >= F2, >= F3, and F4, respectively. There
      was moderate positive correlation between inflammatory activity and T1rho values
      (r = 0.520; 95% CI 0.158-0.807; P = 0.013). CONCLUSION: T1rho imaging has
      potential for liver fibrosis detection and staging with good diagnostic
      capability similar to that of ultrasonography elastography.

PMID- 29198005
TI  - Daughter cyst sign in ovarian cysts.

PMID- 29198006
TI  - Characteristics of PI-RADS 4 lesions within the prostatic peripheral zone: a
      retrospective diagnostic accuracy study evaluating 170 lesions.
AB  - PURPOSE: To determine whether peripheral zone PI-RADS 4 observations can be
      further risk-stratified. METHODS: This was an IRB-approved HIPAA-compliant
      retrospective diagnostic accuracy study. Peripheral zone PI-RADS 4 observations
      prospectively identified at the study institution from 8/1/2015 to 12/31/2016 (n
      = 170 in 149 mpMRIs) were reviewed independently by two blinded genitourinary
      radiologists on the basis of (a) PI-RADS v2 shape, (b) pattern of peripheral zone
      sparing, and (c) rationale for PI-RADS 4 designation. Reference standard was
      targeted MR-ultrasound fusion biopsy and detection of Gleason 7+ prostate cancer.
      Positive predictive values (PPVs) were calculated. Predictors were assessed with
      binary logistic regression. RESULTS: PI-RADS 4 lesions with a DWI score of 4 were
      more likely to represent Gleason 7+ prostate cancer (p = 0.008-0.01; Reader 1
      PPV: 53%; Reader 2 PPV: 48%). Pattern of peripheral zone sparing and most lesion
      shapes were not predictive (p > 0.05); however, oval lesions were predictive for
      Reader 1 (PPV = 59%, p = 0.03) and lentiform lesions were predictive for Reader 2
      (PPV = 74%, p = 0.01). Lesions scored as "not meeting PI-RADS 4 criteria" had
      significantly lower PPV (p = 0.016-0.003; Reader 1 PPV: 14%, Reader 2 PPV: 16%).
      DISCUSSION: Peripheral zone PI-RADS 4 lesions with a DWI score of 4 are more
      likely Gleason 7+ cancer than those with a DWI score of 3. Lesions overcalled as
      PI-RADS 4 have PPV similar to published PI-RADS 3 data. Lesion shape and
      peripheral zone sparing in general do not predict Gleason 7+ cancer within PI
      RADS 4 observations.

PMID- 29198007
TI  - Usefulness of metabolic activity of adipose tissue in FDG PET/CT of colorectal
      cancer.
AB  - PURPOSE: To determine the relationship between metabolic activity of adipose
      tissue on FDG PET/CT and prognosis in colorectal cancer. METHODS: A total of 176
      colorectal cancer patients with curative surgical resection were retrospectively
      enrolled. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and
      visceral adipose tissue (VAT) on FDG PET/CT images were measured. The maximum
      standardized uptake value (SUV) of primary tumor (SUVtumor) was also obtained.
      Univariate analysis with log-rank test and multivariate Cox regression analyses
      were used to evaluate prognostic values of volume and metabolic activity of SAT
      and VAT as well as SUVtumor and clinicopathologic factors. RESULTS: Of 176
      patients, 26 experienced recurrence during follow-up. SUVtumor showed significant
      correlation with serum C-reactive protein level (r = 0.242, p = 0.001), SUV of
      VAT (r = 0.167, p = 0.026), and size of primary tumor (r = 0.341, p < 0.001). In
      univariate analysis with log-rank test, SUV of VAT (p = 0.009) and SAT (p =
      0.006), volume of VAT (p = 0.015), N stage (p < 0.001), M stage (p < 0.001),
      tumor involvement of resection margin (p = 0.001), and lymphatic invasion (p =
      0.024) were significantly associated with recurrence-free survival (RFS).
      However, SUVtumor showed no significant association with RFS. In multivariate Cox
      regression analysis, SUV of VAT (p = 0.016), presence of lymph node metastasis (p
      < 0.001), and tumor involvement of resection margin (p = 0.011) were independent
      prognostic factors for RFS. CONCLUSIONS: The SUV of VAT in patients with
      colorectal cancer is significantly associated with FDG uptake of primary tumor.
      It is an independent predictor for RFS.

PMID- 29198008
TI  - Artifacts in contrast-enhanced ultrasound: a pictorial essay.
AB  - Although contrast-enhanced ultrasound (CEUS) has become a widely utilized and
      accepted modality in much of the world, the associated contrast agents have only
      recently received approval in the United States. As with all radiological
      techniques, image artifacts are encountered in CEUS, some of which relate to
      commonly encountered ultrasound artifacts, while others are unique to this
      technique. Image artifacts must be recognized when performing and interpreting
      examinations to improve technique and diagnostic accuracy. In this article, we
      review artifacts that may be encountered in CEUS, and where possible discuss how
      to minimize them or mitigate their effect on image quality and interpretation.

PMID- 29198009
TI  - The "bouquet of flowers" appearance in medullary sponge kidney.

PMID- 29198010
TI  - Pope's hat sign: another valuable CT finding of early acute cholecystitis.
AB  - PURPOSE: To determine the diagnostic performance of minor computed tomography
      (CT) findings for acute cholecystitis and demonstrate the incremental benefit of
      pope's hat sign as an additional minor CT finding in patients suspected to have
      early acute cholecystitis. MATERIALS AND METHODS: Two radiologists reviewed CT
      scans of 116 patients with early acute cholecystitis and 116 control patients.
      All cases in the patient group were surgically proven to have acute cholecystitis
      and preoperative dynamic CT scans. Evaluated CT parameters included major
      criteria (gallstone, distension of gallbladder (GB) lumen, GB wall edema,
      pericholecystic fat infiltration, and pericholecystic fluid collection) and minor
      criteria (GB bed hyperemia, tensile GB fundus sign, hyperdense GB wall sign,
      increased bile attenuation within GB, and pope's hat sign). RESULTS: In a
      univariate analysis, among the minor criteria, GB bed hyperemia, tensile GB
      fundus sign, increased bile attenuation within GB, and pope's hat sign were more
      frequently observed (P < 0.05) in the early acute cholecystitis group. The
      optimal cut-off value of GB distension for discriminating between the two groups
      was 3.05 cm. In a multivariable analysis, GB bed hyperemia, pope's hat sign, and
      GB lumen > 3.05 cm were significant findings for differentiating the two groups
      (P < 0.001). Among all combinations of these findings, the combination of GB bed
      hyperemia and pope's hat sign exhibited the highest specificity (96.5%) and the
      combination of all three findings showed the highest sensitivity (94.0%).
      CONCLUSION: Pope's hat sign is a new finding that could improve CT diagnostic
      performance for early acute cholecystitis in patients with RUQ pain in the
      emergency department. The combination of pope's hat sign with GB bed hyperemia or
      GB lumen distension > 3.05 cm may be even more helpful in the early stage or in
      mild forms of acute cholecystitis.

PMID- 29198011
TI  - Ovarian collision tumors: imaging findings, pathological characteristics,
      diagnosis, and differential diagnosis.
AB  - Collision tumors are uncommon neoplasms in which elements of differing histologic
      origins coexist in a single mass. Ovarian collision tumors are a rare subtype of
      such lesions. The identification of collision tumors by radiologic examinations
      is essential to ensure that comprehensive biopsies are performed to guide
      appropriate treatments. According to the clinical and imaging findings of 12
      patients and reviews of previous studies, ovarian collision tumors are mixtures
      of different combinations of epithelial tumors, germ cell tumors, and sex-cord
      stromal tumors. The smaller tumors are usually located inside ("nested tumor") or
      on the wall ("back to back") of the larger tumors. Each type of ovarian collision
      tumors presents specific CT/MRI features in accordance with their histologic
      origins and collision patterns. Knowledge of the imaging features of ovarian
      collision tumors is crucial to aid preoperative diagnostic accuracy.

PMID- 29198012
TI  - Successful local treatment for repeated hepatic recurrences of
      cholangiolocellular carcinoma: a report on a long-term survivor.
AB  - BACKGROUND: Cholangiolocellular carcinoma (CoCC) is a rare liver tumor arising
      from the canals of Hering found between the cholangioles and interlobular bile
      ducts. Although morphologically CoCC mimics intrahepatic cholangiocarcinoma
      (ICC), CoCC exhibits a unique intermediate biologic behavior between
      hepatocellular carcinoma (HCC) and ICC. Curative resection is required for
      prolonged survival in patients with CoCC. However, effective therapy for
      postoperative hepatic recurrence has not yet been standardized. CASE
      PRESENTATION: A 40-year-old man had an asymptomatic liver mass found during a
      regular medical examination. Contrast-enhanced computed tomography revealed a
      well-enhanced mass, 15 cm in diameter, in the right liver. He underwent right
      hemihepatectomy at a local hospital under the preoperative diagnosis of
      hepatocellular carcinoma. Pathologic examination confirmed a moderately
      differentiated tubular adenocarcinoma, leading to a diagnosis of ordinary ICC.
      Twelve months after surgery, he was referred to our hospital due to three hepatic
      recurrences in the left medial segment. He underwent partial hepatectomy for the
      recurrence, followed by adjuvant chemotherapy using gemcitabine alone. After the
      second hepatectomy, hepatic recurrences developed an additional seven times. The
      numbers and sizes of the recurrent tumors were very limited at each recurrence,
      satisfying the standard criteria for percutaneous radiofrequency ablation (RFA)
      for the treatment of HCC. All lesions were treated by percutaneous RFA, although
      this was an exceptional approach for ICC. He is now alive without evidence of
      disease 9.2 years after the first hepatectomy. Because his clinical outcome was
      satisfactory and not compatible with the typical negative outcomes of ordinary
      ICC, we re-reviewed the histological findings of his tumor. The tumor was
      composed of small gland-forming cells proliferating in an anastomosing pattern;
      the cell membrane was strongly immunoreactive for epithelial membrane antigen.
      These findings were in accordance with the typical features of CoCC, revising his
      final diagnosis from ICC to CoCC. CONCLUSIONS: This case report demonstrates a
      satisfactory outcome using repeated local treatments, such as hepatectomy and
      RFA, for hepatic recurrences of CoCC, suggesting that a localized treatment
      approach can be considered to be a therapeutic option. We should be careful in
      making a definitive diagnosis of ICC and ruling out CoCC because the diagnosis
      potentially dictates the treatment strategy for recurrences.

PMID- 29198013
TI  - Short- and Long-Term Protective Effects of Melatonin in a Mouse Model of Sepsis
      Associated Encephalopathy.
AB  - Brain dysfunction is a common complication after sepsis and is an independent
      risk factor for a poor prognosis, which is partly attributed to the dysregulated
      inflammatory response and oxidative damage. Melatonin regulates the sleep-wake
      cycle and also has potent anti-inflammatory and antioxidant properties, yet the
      protective effects of melatonin on sepsis-induced neurobehavioral dysfunction
      remain to be elucidated. In the present study, melatonin was administered
      intraperitoneally daily at a dose of 10 mg/kg for three consecutive days
      immediately (early treatment) or 7 days (delayed treatment) after sham operation
      or cecal ligation and puncture (CLP), followed by an additional treatment in
      drinking water until the end of behavioral tests. The concentrations of pro
      inflammatory cytokines (tumor necrosis factor (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6, IL-10), malondialdehyde (MDA), superoxide dismutase (SOD), reactive
      oxygen species (ROS), brain-derived neurotrophic factor (BDNF), and glial cell
      line-derived neurotrophic factor (GDNF) were determined at the indicated time
      points. Compared with the CLP + vehicle group, we found that early melatonin
      treatment resulted in increased survival rate but not improvement in measures of
      neurobehavioral outcomes, which was accompanied by significantly lower plasma
      level of IL-1beta. Intriguingly, delayed melatonin treatment improved
      neurobehavioral dysfunction by normalization of hippocampal BDNF and GDNF
      expressions. In conclusion, our study suggests the beneficial effects of both
      early and delayed melatonin treatment after sepsis development, which implicates
      melatonin has a potential therapeutic value in sepsis-associated organ damage
      including brain dysfunction.

PMID- 29198014
TI  - Inhibition of Complement Drives Increase in Early Growth Response Proteins and
      Neuroprotection Mediated by Salidroside After Cerebral Ischemia.
AB  - Salidroside is neuroprotective across a wide therapeutic time-window after
      cerebral ischemia-reperfusion injury (IRI). Here, we investigated the role of
      complement in mediating effects of salidroside after cerebral IRI in rats. Rats
      were administrated with vehicle or salidroside 50 mg/kg, given daily for either
      24 or 48 h, after middle cerebral artery occlusion (MCAO) for 2 h and reperfusion
      for 1 h. Levels of proteins in ischemic brain were measured by immunofluorescence
      and western blotting. We observed early increases in the deposition of
      immunoglobulin M, mannose-binding lectin 2, and annexin IV on cerebral
      endothelial cells, induction of the complement components C3 and C3a, by 24 h
      after IRI, and a later significant increase in the complement component C1q by 48
      h. Salidroside prevented these changes. The neuroplasticity-related early growth
      response proteins Egr1, Egr2, and Egr4 and activity-regulated cytoskeleton
      associated protein increased transiently in the first 6 h after IRI but then
      decreased below baseline by 48 h after IRI. Neither salidroside nor a C3a
      receptor antagonist (C3aRA) affected these proteins 24 h after IRI, but both
      reversed their later decreases to similar and non-additive extents. Salidroside
      and C3aRA increased NeuN in a non-additive manner after IRI. Our results suggest
      that salidroside exerts neuroprotection by reducing early activation of the
      lectin pathway on the cerebral endothelium and inhibiting the gradual activation
      of the classical pathway after cerebral IRI. This prolonged neuroprotection may
      depend, at least in part, on increased expression of neuroplasticity-related
      genes driven by reduced complement activation.

PMID- 29198015
TI  - The Anti-inflammatory Effects of 4-((5-Bromo-3-chloro-2-hydroxybenzyl) amino)-2
      hydroxybenzoic Acid in Lipopolysaccharide-Activated Primary Microglial Cells.
AB  - Over-activated microglial cells are known to be implicated in various
      neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease
      (PD), and multiple sclerosis. Our previous reports have shown that ZL006, a
      compound with a hydrophobic ring A and a hydrophilic ring B with a carboxyl
      group, exhibited stronger neuroprotective activity in vitro and in vivo. However,
      the directly anti-inflammatory effects of these compounds in the central nervous
      system (CNS) have not been elucidated. In the present study, as a part of our
      ongoing screening experiment to evaluate the anti-inflammatory effects of new
      compounds, a newly synthesized 4-((5-bromo-3-chloro-2-hydroxybenzyl) amino)-2
      hydroxybenzoic acid (LX007) was used to examine whether it could reduce the
      inflammatory responses of activated microglia. Our results indicated that LX007
      inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and prostaglandin
      E2 (PGE2) expression, as well as their regulatory gene-inducible NO syntheses
      (iNOS) and cyclooxygenase-2 (COX-2) in LPS-treated primary microglia. LPS-induced
      production from microglia of interleukin (IL)-1beta, IL-6, and tumor necrosis
      factor (TNF-alpha) was also significantly attenuated by LX007. Mechanistically,
      LX007 potently suppressed phosphorylation of mitogen-activated protein kinases
      (MAPKs) and nuclear factor-kappa B (NF-kappaB) p65 nuclear translocation in LPS
      induced microglia. We therefore conclude that LX007 exhibits anti-inflammatory
      effects in LPS-stimulated microglial cells by inhibiting pro-inflammatory
      mediators corresponding to the downregulating of MAPKs and NF-kappaB activation.
      Taken together, the present study indicated that LX007 may have potential to be
      developed into an anti-inflammatory agent in the future.

PMID- 29198017
TI  - Low pH irrigation fluids have positive effect on intra-articular chondral
      healing.
AB  - PURPOSE: The aim of this study was to evaluate the effect of Ringer's lactate
      (RL) solutions with different pH values on early histologic healing in a
      microfracture model in vivo. The null hypothesis of the presented study is that
      irrigation fluids with lower pH (6.4) have negative effects on fibrous cartilage
      healing. METHODS: Eighteen Wistar albino rats were randomly divided into three
      groups. Anterior midline incision was performed. Microfracture procedure was
      performed with a 1.2 mm k-wire at the lateral femoral condyle of each knee. the
      skin was sutured and joints were irrigated for 30 min with low pH (6.4) RL in
      Group 1, high pH (7.6) RL in Group 2 and no irrigation in Group 3. Three rats
      from each group were randomly selected and killed on the 3rd and 7th day. On the
      3rd day, the healed chondral area was examined. On the 3rd and 7th day, the
      chondral depth and morphology were evaluated. On the 7th day, bone cellularity
      was assessed with osteoblast; osteoclast number and bone quality were evaluated
      with trabecular area and the number of trabeculae. RESULTS: Chondral healing area
      on the 3rd day was significantly higher in Group 1 compared to other groups.
      Chondral morphology was also qualitatively superior in Group 1 compared to other
      groups on the 3rd and 7th day. There were no differences in chondral depths
      between the groups on the 3rd day; however, increased chondral depths were
      observed in Group 1 on the 7th day. There were statistically significant
      increases in trabecular area and the number of trabeculae, as well as the number
      of osteoblasts and osteoclasts in Group 1 on the 7th day. CONCLUSIONS: The
      presented study revealed that low pH irrigation fluids have positive effects on
      the healing characteristics of intra-articular fibrous cartilage after
      microfracture procedure in vivo. In light of this study, we can assume that lower
      pH solutions could be safely used during microfracture procedures and it can also
      facilitate intra-articular fibrous cartilage formation and cartilage healing.
      Selection of irrigation solution is also important for intra-articular fibrous
      cartilage healing after microfracture procedure in vivo.

PMID- 29198016
TI  - Advantages and limitations of multiple-trait genomic prediction for Fusarium head
      blight severity in hybrid wheat (Triticum aestivum L.).
AB  - KEY MESSAGE: Predictabilities for wheat hybrids less related to the estimation
      set were improved by shifting from single- to multiple-trait genomic prediction
      of Fusarium head blight severity. Breeding for improved Fusarium head blight
      resistance (FHBr) of wheat is a very laborious and expensive task. FHBr
      complexity is mainly due to its highly polygenic nature and because FHB severity
      (FHBs) is greatly influenced by the environment. Associated traits plant height
      and heading date may provide additional information related to FHBr, but this is
      ignored in single-trait genomic prediction (STGP). The aim of our study was to
      explore the benefits in predictabilities of multiple-trait genomic prediction
      (MTGP) over STGP of target trait FHBs in a population of 1604 wheat hybrids using
      information on 17,372 single nucleotide polymorphism markers along with indicator
      traits plant height and heading date. The additive inheritance of FHBs allowed
      accurate hybrid performance predictions using information on general combining
      abilities or average performance of both parents without the need of markers.
      Information on molecular markers and indicator trait(s) improved FHBs
      predictabilities for hybrids less related to the estimation set. Indicator traits
      must be observed on the predicted individuals to benefit from MTGP. Magnitudes of
      genetic and phenotypic correlations along with improvements in predictabilities
      made plant height a better indicator trait for FHBs than heading date. Thus, MTGP
      having only plant height as indicator trait already maximized FHBs
      predictabilities. Provided a good indicator trait was available, MTGP could
      reduce the impacts of genotype environment [Formula: see text] interaction on
      STGP for hybrids less related to the estimation set.

PMID- 29198018
TI  - Fate of coracoid grafts after the Latarjet procedure: will be analogous to the
      original glenoid by remodelling.
AB  - PURPOSE: To evaluate the location, magnitude, and change over time of osteolysis
      of coracoid grafts after Latarjet procedure. METHODS: This is a retrospective
      study of 54 patients (55 shoulders) who underwent the Latarjet procedure. Three
      dimensional computed tomography (CT) scans were performed preoperatively,
      immediately postoperatively, and at follow-up (mean 7.7 and 31.7 months
      postoperative). "En face" views of the glenoid, size of glenoid defect and
      changes in the glenoid surface area postoperatively were measured relative to the
      area of an assumed outer-fitting circle. On the oblique sagittal planes, location
      and subsequent severity of osteolysis of the graft at follow-up were documented.
      RESULTS: The mean glenoid surface area increased significantly from 79.7 +/- 4.8%
      of the original circle preoperatively to 111.3 +/- 8.0% immediately
      postoperatively. At 7.7 and 31.7 months of follow-up, glenoid surface area
      decreased to 102.2 +/- 6.0% and 100.3 +/- 5.3%, respectively. Osteolysis occurred
      on the outer side of the graft in all cases, but did not occur on the inner side.
      Maximum osteolysis was observed in the superior third of the graft (78.5 +/-
      17.1%), followed by the middle third (15.8 +/- 10.4%), and the inferior third
      (8.0 +/- 5.1%). No significant difference in magnitude of osteolysis was observed
      between 7.7 and 31.7 months of follow-up. CONCLUSION: Osteolysis of the grafted
      coracoid mainly occurred on the outer side of the superior portion, resulting in
      reshaping of the rectangular shape of graft coracoids after Latarjet procedure.
      Coracoid graft remodelling was almost completed approximately 8 months
      postoperatively to reach the original glenoid dish with no further changes
      thereafter. These results may help surgeons to understand changes of grafts after
      the surgery. LEVEL OF EVIDENCE: IV.

PMID- 29198019
TI  - Muscle proteolytic system modulation through the effect of taurine on mice
      bearing muscular atrophy.
AB  - Skeletal muscle atrophy occurs in different catabolic conditions and mostly
      accompanied with upregulation of Muscle ring finger 1 (MuRF1) gene which is one
      of the master regulatory genes in muscle atrophy. Taurine amino acid is widely
      distributed in different tissues and has anti-inflammatory and antioxidant
      effects. This study aimed to investigate the potential influence of taurine on
      muscle atrophy induced by reduced mechanical loading. Twenty-eight Albino mice
      were used, and divided equally into four groups: group I (control); group II
      (immobilization); group III (immobilization + taurine); and group IV (taurine).
      Quadriceps muscle sections were taken for histopathology, immunohistochemical
      analysis of caspase 3 expression, and qRT-PCR of MuRF1 gene. Our data revealed
      Zenker necrosis associated with axonal injury of the nerve trunk of the
      immobilized muscle together with increase of caspase 3 expression and
      upregulation of MuRF1 gene. While, taurine supplementation alleviated the
      muscular and neural tissues damage associated with disuse skeletal muscle atrophy
      through downregulation of MuRF1 gene and decrease of tissue caspase 3 expression.
      In conclusion, taurine may be helpful to counteract apoptosis and up-regulated
      MuRF1 gene expression related to muscle atrophy, which might be hopeful for a
      large number of patients.

PMID- 29198020
TI  - Identification of a novel intergenic miRNA located between the human DDC and COBL
      genes with a potential function in cell cycle arrest.
AB  - Frequent abnormalities in 7p12 locus in different tumors like lung cancer
      candidate this region for novel regulatory elements. MiRNAs as novel regulatory
      elements encoded within the human genome are potentially oncomiRs or miR
      suppressors. Here, we have used bioinformatics tools to search for the novel
      miRNAs embedded within human chromosome 7p12. A bona fide stem loop (named mirZa
      precursor) had the features of producing a real miRNA (named miRZa) which was
      detected through RT-qPCR following the overexpression of its precursor. Then,
      endogenous miRZa was detected in human cell lines and tissues and sequenced.
      Consistent to the bioinformatics prediction, RT-qPCR as well as dual luciferase
      assay indicated that SMAD3 and IGF1R genes were targeted by miRZa. MiRZa-3p and
      miRZa-5p were downregulated in lung tumor tissue samples detected by RT-qPCR, and
      mirZa precursor overexpression in SW480 cells resulted in increased sub-G1 cell
      population. Overall, here we introduced a novel miRNA which is capable of
      targeting SMAD3 and IGF1R regulatory genes and increases the cell population in
      sub-G1 stage.

PMID- 29198021
TI  - Alpha-synuclein aggregation, Ubiquitin proteasome system impairment, and L-Dopa
      response in zinc-induced Parkinsonism: resemblance to sporadic Parkinson's
      disease.
AB  - Alpha-synuclein (alpha-synuclein) aggregation and impairment of the Ubiquitin
      proteasome system (UPS) are implicated in Parkinson's disease (PD) pathogenesis.
      While zinc (Zn) induces dopaminergic neurodegeneration resulting in PD phenotype,
      its effect on protein aggregation and UPS has not yet been deciphered. The
      current study investigated the role of alpha-synuclein aggregation and UPS in Zn
      induced Parkinsonism. Additionally, levodopa (L-Dopa) response was assessed in Zn
      induced Parkinsonian model to establish its closeness with idiopathic PD. Male
      Wistar rats were treated with zinc sulfate (Zn; 20 mg/kg; i.p.) twice weekly for
      12 weeks along with respective controls. In few subsets, animals were
      subsequently treated with L-Dopa for 21 consecutive days following Zn exposure. A
      significant increase in total and free Zn content was observed in the substantia
      nigra of the brain of exposed groups. Zn treatment caused neurobehavioral
      anomalies, striatal dopamine decline, and dopaminergic neuronal cell loss
      accompanied with a marked increase in alpha-synuclein expression/aggregation and
      Ubiquitin-conjugated protein levels in the exposed groups. Zn exposure
      substantially reduced UPS-associated trypsin-like, chymotrypsin-like, and caspase
      like activities along with the expression of SUG1 and beta-5 subunits of UPS in
      the nigrostriatal tissues of exposed groups. L-Dopa treatment rescued from Zn
      induced neurobehavioral deficits and restored dopamine levels towards normalcy;
      however, Zn-induced dopaminergic neuronal loss, reduction in tyrosine hydroxylase
      expression, and increase in oxidative stress were unaffected. The results suggest
      that Zn caused UPS impairment, resulting in alpha-synuclein aggregation
      subsequently leading to dopaminergic neurodegeneration, and that Zn-induced
      Parkinsonism exhibited positive L-Dopa response similar to sporadic PD.

PMID- 29198022
TI  - Hyperthyroid patients without Graves' orbitopathy are not at increased risk of
      developing glaucoma: a nationwide Danish register-based case-control study.
AB  - PURPOSE: Graves' disease (GD) and toxic nodular goiter (TNG) are associated with
      various comorbidities. However, it is unclarified whether TNG and GD without
      orbitopathy are associated with glaucoma. METHODS: This was a case-control study
      using record-linkage data from nationwide Danish health registers. 28,461
      patients with GD and 17,283 with TNG were included. Each case was age and sex
      matched with four non-hyperthyroid controls and followed over a mean period of 8
      years. Data on glaucoma was obtained by record linkage within the National Danish
      Patient Register and/or the Danish National Prescription Registry. Logistic and
      Cox regression models were used to assess the risk of glaucoma before and after
      the diagnosis of GD and TNG. RESULTS: Compared to controls, there was a
      significantly increased frequency of glaucoma in patients with GD (4.6 vs. 4.2%,
      P = 0.006) and in patients with TNG (6.2 vs. 5.7%, P = 0.003). Prior to the
      diagnosis of hyperthyroidism, the odds ratio (OR) for glaucoma was non
      significant in GD (1.09, 95% CI: 1.00-1.18) but slightly increased in TNG (1.13,
      95% CI: 1.02-1.24). However, in TNG the OR attenuated completely when only
      including patients without co-morbidity in the analysis (1.03, 95% CI: 0.93
      1.14). After adjustment for pre-existing co-morbidity, the hazard ratio (HR) for
      glaucoma following GD and TNG was not significantly increased (HR 1.08, 95% CI:
      0.98-1.18 and HR 1.10, 95% CI: 0.99-1.21, respectively). CONCLUSIONS: Neither
      prior to nor following the diagnosis of GD and TNG had any significant
      association with glaucoma.

PMID- 29198023
TI  - The Use of Stimulant Medication to Treat Attention-Deficit/Hyperactivity Disorder
      in Elite Athletes: A Performance and Health Perspective.
AB  - The use of stimulants as a treatment for attention-deficit/hyperactivity disorder
      (ADHD) among elite athletes is a controversial area with some arguing that
      stimulant use should not be permitted because it offers an advantage to athletes
      (fair play perspective). Guided by an integrated model of athletic performance,
      we address common concerns raised about stimulant use in sports from our
      perspective, which we coined the "performance and health perspective,"
      highlighting relevant research and pointing to gaps in empirical research that
      should be addressed before bans on use of stimulants for athletes with ADHD are
      considered. The current article posits that a stimulant ban for athletes with
      ADHD does not necessarily facilitate fair play, ensure safety, or align with
      existing policies of large governing bodies. Instead, we recommend that stimulant
      medication be allowed in high-level sport, following proper diagnosis by a
      trained professional and a cardiac assessment to confirm no underlying heart
      conditions. Athletes with ADHD approved to use stimulant medication should be
      monitored by a health care professional, physically reevaluated and reassessed
      for ADHD as clinically appropriate and as indicated by relevant sports governing
      bodies. This performance and health perspective is consistent with that of
      multiple sport governing bodies who offer therapeutic use.

PMID- 29198024
TI  - Application of phototrophic biofilms: from fundamentals to processes.
AB  - Biotechnological production of valuables by microorganisms is commonly achieved
      by cultivating the cells as suspended solids in an appropriate liquid medium.
      However, the main portion of these organisms features a surface-attached growth
      in their native habitats. The utilization of such biofilms shows significant
      challenges, e.g. concerning control of pH, nutrient supply, and heat/mass
      transfer. But the use of biofilms might also enable novel and innovative
      production processes addressing robustness and strength of the applied
      biocatalyst, for example if variable conditions might occur in the process or a
      feedstock (substrate) is changed in its composition. Besides the robustness of a
      biofilm, the high density of the immobilized biocatalyst facilitates a simple
      separation of the catalyst and the extracellular product, whereas intracellular
      target compounds occur in a concentrated form; thus, expenses for downstream
      processing can be drastically reduced. While phototrophic organisms feature a
      fabulous spectrum of metabolites ranging from biofuels to biologically active
      compounds, the low cell density of phototrophic suspension cultures is still
      limiting their application for production processes. The review is focusing on
      pro- and eukaryotic microalgae featuring the production of valuable compounds and
      highlights requirements for their cultivation as phototrophic biofilms, i.e.
      setup as well as operation of biofilm reactors, and modeling of phototrophic
      growth.

PMID- 29198025
TI  - Characteristics of polycyclic aromatic hydrocarbons in PM2.5 emitted from
      different cooking activities in China.
AB  - Nineteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 emitted from five
      different cooking activities were characterized, and their influencing factors
      were determined. The total quantified particle-bounded PAH concentrations
      (SigmaPAHs) in the airs from the cooking activities were 4.2-36.5-fold higher
      than those in corresponding backgrounds. The highest SigmaPAHs were seen in
      cafeteria frying (783 +/- 499 ng/m3), followed by meat roasting (420 +/- 191
      ng/m3), fish roasting (210 +/- 105 ng/m3), snack-street boiling (202 +/- 230
      ng/m3), and cafeteria boiling (150 +/- 65 ng/m3). The main influencing factors on
      the PAH emissions were cooking methods, fat contents in raw materials, and oil
      consumptions. Four- to six-ringed PAHs had the highest contributions to the
      SigmaPAHs (avg. 87.5%). Diagnostic ratios of individual PAH were similar between
      the two charbroiling and other three conventional Chinese cooking methods,
      respectively, demonstrating the dominance of cooking methods in the PAH
      emissions. Remarkably high benzo(b)fluoranthene/benzo(k)fluoranthene (BbF/BkF)
      ratio (8.31) was seen in the snack-street boiling, attributed to the coal
      combustion as cooking fuel. Both fluoranthene/(fluoranthene + pyrene) [FLT/(FLT +
      PYR)] and benzo(a)anthracene/(benzo(a)anthracene + chrysene) [BaA/(BaA + CHR)]
      ratios were higher for the oil-based cooking than those from the water-based
      ones. In addition, two ratios of indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene +
      benzo(g,h,i)perylene) [IPY/(IPY + BPE)] and benzo(a)pyrene/(benzo(a)pyrene +
      benzo(g,h,i)perylene) [BaP/(BaP + BPE)] were higher for two charbroiling than the
      three conventional Chinese cooking methods. The characterization work in this
      study is particularly important since cooking is a potential contributor of
      atmospheric PAHs in urban China. Carcinogenic potencies of PAHs were assessed by
      comparison with the air quality guideline and health risk estimation. The BaP and
      BaP equivalent were higher for the oil-based than the water-based cooking
      activities.

PMID- 29198026
TI  - The synthetic evaluation of CuO-MnOx-modified pinecone biochar for simultaneous
      removal formaldehyde and elemental mercury from simulated flue gas.
AB  - A series of low-cost Cu-Mn-mixed oxides supported on biochar (CuMn/HBC)
      synthesized by an impregnation method were applied to study the simultaneous
      removal of formaldehyde (HCHO) and elemental mercury (Hg0) at 100-300 degrees  C
      from simulated flue gas. The metal loading value, Cu/Mn molar ratio, flue gas
      components, reaction mechanism, and interrelationship between HCHO removal and
      Hg0 removal were also investigated. Results suggested that 12%CuMn/HBC showed the
      highest removal efficiency of HCHO and Hg0 at 175 degrees  C corresponding to
      89%and 83%, respectively. The addition of NO and SO2 exhibited inhibitive
      influence on HCHO removal. For the removal of Hg0, NO showed slightly positive
      influence and SO2 had an inhibitive effect. Meanwhile, O2 had positive impact on
      the removal of HCHO and Hg0. The samples were characterized by SEM, XRD, BET,
      XPS, ICP-AES, FTIR, and H2-TPR. The sample characterization illustrated that
      CuMn/HBC possessed the high pore volume and specific surface area. The
      chemisorbed oxygen (Obeta) and the lattice oxygen (Oalpha) which took part in the
      removal reaction largely existed in CuMn/HBC. What is more, MnO2 and CuO (or
      Cu2O) were highly dispersed on the CuMn/HBC surface. The strong synergistic
      effect between Cu-Mn mixed oxides was critical to the removal reaction of HCHO
      and Hg0 via the redox equilibrium of Mn4+ + Cu+ <-> Mn3+ + Cu2+.

PMID- 29198027
TI  - Estimation of sodium adsorption ratio indicator using data mining methods: a case
      study in Urmia Lake basin, Iran.
AB  - Water quality is a major concern around the world, particularly in dry climates.
      Usually, assessment of surface water quality is costly and time-consuming. In
      this situation, a method which could estimate the water quality accurately with
      the minimum of hydro-chemical parameters would be appealing. In this study, three
      data mining methods, namely, M5 model tree, support vector machine (SVM), and
      Gaussian process (GP), were employed to estimate the sodium adsorption ratio
      (SAR) indicator in the Shahrchay River located in the west of the Urmia Lake
      basin, Iran. Results from these methods were compared with an artificial neural
      network (ANN). Different hydro-chemical parameters were assessed and the most
      effective parameters were selected. Five combinations of the selected parameters
      were developed as input parameters to the models. The results indicated that the
      M5 model tree has a superior performance among the data mining methods, where the
      combination of sodium and electrical conductivity (Na and EC) is used as input
      parameters, with a coefficient of determination (R2) = 0.987, root mean squared
      error (RMSE) = 0.017, mean absolute error (MAE) = 0.012, and mean relative error
      (MRE) = 5.584. Also, a sensitivity analysis was carried out which reported that
      the SAR is more sensitive to Na, Ca, and EC, respectively. This research
      highlights that the M5 model tree can be successfully employed for the estimation
      of SAR. It also indicates that the practical and simple linear equations and
      optimization performed with the M5 model tree reduce time and cost.

PMID- 29198028
TI  - Adverse bioeffect of perfluorooctanoic acid on liver metabolic function in mice.
AB  - Perfluorooctanoic acid (PFOA), a kind of manufactured material, is widely
      accumulated around environmental system and into wildlife, including human
      beings. Toxicologically, PFOA induces hepatomegaly (liver enlargement) in the
      dose- and time-dependent manners. However, biological mechanism of hepatotoxicity
      warrants to be further investigated. In the present study, mature male mice were
      exposed to dosed PFOA for 21 days before conducting biochemical tests and
      immunoassays. As results, decreased fast blood glucose and elevated insulin
      contents were observed in PFOA-dosed mice. In addition, PFOA-dosed mice resulted
      in increased liver functional enzymes (GPT, GOT) in serum. And lipid contents
      (TG, lipoproteins) in serum and liver were changed abnormally. As shown in
      immunohistochemistry, increased insulin- and poly (ADP-ribose) polymerase (PARP)
      positive cells were showed in PFOA-exposed pancreatic tissues. Moreover, CD36
      positive cells were increased in PFOA-exposed livers, while ApoB-labeled cells
      were reduced. Further, immunoblot data showed that hepatocellular fibroblast
      growth factor 21 (FGF21) in PFOA-exposed liver was down-regulated dose
      dependently. Taken together, our preliminary findings demonstrated that PFOA
      induced hepatocellular lipotoxicity may be linked to impairing lipid-regulated
      proteins, as well as inducing insulin expression from pancreatic tissue.

PMID- 29198029
TI  - High temperature and pH favor Microcystis aeruginosa to outcompete Scenedesmus
      obliquus.
AB  - Competition between cyanobacteria and green algae affects phytoplankton
      succession and the well-known cyanobacteria blooms. Climate warming and water
      acidification are two concerned environmental issues changing the freshwater
      ecosystems. To investigate the competitive responses of phytoplankton to warming
      and acidification, we co-cultured Microcystis aeruginosa and Scenedesmus obliquus
      at a temperature range of 15-35  degrees C and a pH range of 5-9. Results showed
      that S. obliquus was superior competitor at 15  degrees C. At 20-30  degrees C,
      the populations of both Scenedesmus and Microcystis were inhibited by the
      presence of each other. S. obliquus was in competitive domination at the initial
      phase of cultivation, but was finally replaced by M. aeruginosa. Microcystis kept
      competition advantage at 35  degrees C, whereas Scenedesmus outcompeted
      Microcystis at acidic conditions (pH <= 6). Neutral and weakly alkaline
      conditions (pH 7-9) supported the replacement of competition domination from
      Scenedesmus to Microcystis. The present study revealed that climate warming may
      accelerate the phytoplankton succession from green algae to cyanobacteria, with
      the predicted promoted cyanobacteria blooms. Nonetheless, water acidification
      causes Microcystis to be a weak competitor with green algae, suggesting that the
      advantageous effect of Microcystis toward green algae at high temperatures was
      controlled by other variables like the water pH.

PMID- 29198030
TI  - Adsorptive performance of coal-based magnetic activated carbon for cyclic
      volatile methylsiloxanes from landfill leachate.
AB  - Bituminous coal-based magnetic activated carbon (MAC) was prepared,
      characterized, and used successfully for removal of cyclic volatile
      methylsiloxanes (cVMSs) from treated landfill leachate. Batch adsorption studies
      were performed at different adsorption dosages and contact times. With adsorptive
      dosage of 0.75 g/L and contact time of 60 min, the removal efficiencies achieved
      by MAC for octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5),
      and dodecamethylcyclohexasiloxane (D6) are 100, 82.8, and 71.4%, respectively.
      The specific magnetization coefficients of MAC before and after adsorption are
      4.6 * 10-7 and 5.2 * 10-7 m3/kg, between 1.26 * 10-7 and 3.8 * 10-5 m3/kg, which
      suggests that MAC can be recycled by the high-intensity magnetic separators.

PMID- 29198031
TI  - Metatranscriptomics analysis of cyanobacterial aggregates during cyanobacterial
      bloom period in Lake Taihu, China.
AB  - Molecular mechanism of interaction between the bloom-forming cyanobacterial
      species and attached microbios within cyanobacterial aggregates has not been
      elucidated yet and understanding of which would help to unravel the cyanobacteria
      bloom-forming mechanism. In this study, we profiled the metabolically active
      community by high-throughput metatranscriptome sequencing from cyanobacterial
      aggregates during cyanobacterial bloom period in Lake Taihu, China. A total of
      308 million sequences were obtained using the HiSeq 2500 sequencing platform,
      which provided a great sequence coverage to carry out the in-depth taxonomic
      classification, functional classification, and metabolic pathway analysis of the
      cyanobacterial aggregates. The results show that bacteria dominated in
      cyanobacterial aggregates, accounting for more than 96.66% of total sequences.
      Microcystis was the most abundant genus, accounted for 26.80% of total assigned
      sequences at the genus level in cyanobacterial aggregates community; however,
      Proteobacteria (46.20%) was found to be as the most abundant active bacterial
      populations at the phylum level. More importantly, nitrogen, phosphonate, and
      phosphinate metabolism which associated with eutrophication were found in this
      study. Especially, the enzymes and organisms relating to denitrification and
      anammox of nitrogen metabolism, which reduced nitrogen concentration by reducing
      nitrate to nitrogen to inhibit the eutrophication, were first discovered in Lake
      Taihu during cyanobacterial bloom period. The present study provides a snapshot
      of metatranscriptome for cyanobacterial aggregates in Lake Taihu and demonstrates
      that cyanobacterial aggregates could play a key role in the nitrogen cycle in
      eutrophic water.

PMID- 29198032
TI  - Evolution of natural sea surface films: a new quantification formalism based on
      multidimensional space vector.
AB  - Spatial and temporal variability of natural surfactant sea surface film
      structural parameters were evaluated from force-area isotherms, film pressure
      temperature isochors, dynamic surface tension-time relations performed on samples
      collected in Baltic Sea shallow coastal waters. The film structure state was
      postulated as a 10-D dimensionless vector created from the normalized
      thermodynamic, adsorptive, and viscoelastic film parameters. The normalization
      procedure is based on the concept of self-corresponding states known in
      thermodynamics. The values taken by all the reduced parameters indicated a
      significant deviation from the reference ideal-2D gas behavior. The exhibited
      deviations of the surface parameters from the background values of the same
      thermodynamic state of each film were independent on the film-collecting
      procedure, sample solvent treatment, and temperature. The structural similarity
      was expressed quantitatively as a (Cartesian, street, and Czebyszew) distance
      between two vectors of the analyzed film and the standard one from the database,
      and appeared to be related to environmental conditions, surface-active organic
      matter production, and migration in the studied coastal sea region. The most
      distinctive parameters differing the films were y, M w and E isoth, as
      established from Czebyszew function application. The proposed formalism is of
      universal concern and could be applied to any natural water surfactant system
      (seawater, inland water, rain water, and snowmelt water).

PMID- 29198033
TI  - All that glitters is not gold - new reconstruction methods using Deauville
      criteria for patient reporting.

PMID- 29198034
TI  - Population-level effect of molecular testing and targeted therapy in patients
      with advanced pulmonary adenocarcinoma: a prospective cohort study.
AB  - Large cancer centres in the USA demonstrated that molecular diagnosis and
      targeted therapy improved overall survival of patients with advanced pulmonary
      adenocarcinoma. We validated this finding in a rural area of Switzerland, served
      by private practices, community hospitals and a tertiary referral centre. We
      conducted a prospective cohort study with the Cancer Registry of Central
      Switzerland, covering 4 cantons and 517,000 inhabitants. All residents newly
      diagnosed with stage IV pulmonary adenocarcinoma from 2010 to 2014 were enrolled.
      We obtained information on patients, tumour, molecular testing, therapy and
      survival. Three hundred forty-eight patients were included in the study.
      Molecular testing was performed in 279 (80%); 132 (38%) had oncogenic driver
      mutations: Kirsten rat sarcoma (KRAS, 16%), epidermal growth factor receptor
      (EGFR, 11%), anaplastic lymphoma kinase (ALK, 5%), human epidermal growth factor
      receptor 2 (HER2, 2%), B rapidly accelerated fibrosarcoma (BRAF, 1%), rearranged
      during transfection (RET, 0.5%), MET proto-oncogene (0.5%) and multiple mutations
      (2%). Fifty-six patients with an oncogenic driver mutation, mostly epidermal
      growth factor receptor (34) and anaplastic lymphoma kinase (12), received
      genotype-matched targeted therapy, at least 25 (45%) of whom in a clinical trial
      or named patient programme. Median overall survival was 18 months for patients
      with driver mutations and targeted therapy, 8 months for patients with driver
      mutations and conventional therapy and 10 months for patients with no driver
      mutation and conventional therapy. For patients with driver mutations and
      targeted therapy, overall survival was significantly better than that for
      patients with driver mutations and conventional therapy (HR 0.64, p = 0.04).
      Rigorous testing combined with optimal access to targeted therapy in clinical
      trials improved the prognosis of patients with advanced pulmonary adenocarcinoma
      in Central Switzerland. This effect was mainly driven by therapies targeting
      epidermal growth factor receptor and anaplastic lymphoma kinase.

PMID- 29198035
TI  - Favorable response of relapsed/refractory gray-zone lymphoma to brentuximab
      vedotin.

PMID- 29198036
TI  - Detection of hepatitis B virus DNA and HBsAg from postmortem blood and
      bloodstains.
AB  - A large number of accidental virus infections occur in medical and non-medical
      workers exposed to infectious individuals and materials. We evaluated whether
      postmortem blood and bloodstains containing hepatitis B virus (HBV) are
      infectious. HBV-infected blood and bloodstains were stored for up to 60 days at
      room temperature and subsequently screened for hepatitis B surface antigen
      (HBsAg) and HBV DNA. In addition, HBV-positive postmortem blood was added to a
      cell line and the production of HBV virions was examined over a period of 7 days.
      HBsAg and HBV DNA were detected in all samples stored for 60 days at room
      temperature. HBV-positive postmortem blood successfully infected the cell line
      and progeny viruses were produced for up to 6 days. Thus, it is crucial that due
      care is taken when handling not only living material infected with HBV, as well
      as other harmful viruses, but also blood or body fluids from cadavers or medical
      waste.

PMID- 29198037
TI  - Gene expression profile and long non-coding RNA analysis, using RNA-Seq, in
      chicken embryonic fibroblast cells infected by avian leukosis virus J.
AB  - Avian leukosis virus J (ALVJ) infection induces hematopoietic malignancy in
      myeloid leukemia and hemangioma in chickens. However, little is known about the
      mechanisms underpinning the unique pathogenesis of ALVJ. In this study, we
      investigated the gene expression profiles of ALVJ-infected chicken cells and
      performed a comprehensive analysis of the long non-coding RNAs (lncRNAs) in CEF
      cells using RNA-Seq. As a result, 36 differentially expressed lncRNAs and 91
      genes (FC > 2 and q-values < 0.05) were identified. Bioinformatics analysis
      revealed that these differentially expressed genes are involved in the innate
      immune response. Target prediction analysis revealed that these lncRNAs may act
      in cis or trans and affect the expression of genes which are involved in the anti
      viral innate immune responses. Toll-like receptor, RIG-I receptor, NOD-like
      receptor and JAK-STAT signaling pathways were enriched. Notably, the induced
      expression of innate immunity genes, including B2M, DHX58, IFI27L2, IFIH1, IRF10,
      ISG12(2), MX, OAS*A, RSAD2, STAT1, TLR3, IL4I1, and IRF1 (FC > 2 and correlation
      > 0.95), were highly correlated with the upregulation of several lncRNAs,
      including MG066618, MG066617, MG066601, MG066629, MG066609 and MG066616. These
      findings identify the expression profile of lncRNAs in chicken CEF cells infected
      by ALVJ virus and provide new insights into the molecular mechanisms of ALVJ
      infection.

PMID- 29198038
TI  - Photosynthetic gas exchange responses of Swietenia macrophylla King and Melia
      azedarach L. plantations under drought conditions.
AB  - BACKGROUND: The environmental stresses caused by climate change have become more
      severe in recent decades, affecting tree growth and physiology. Tropical forests
      have great potential for global carbon sequestration. However, they suffer from
      heavy rainfall and prolonged dry periods due to climate change. Swietenia
      macrophylla King and Melia azedarach L. are economically valuable trees that are
      widely planted in southern Taiwan. Plantations are exposed to either prolonged
      dry periods or heavy rainfall within the seasons of tropical monsoon areas. Photo
      physiological comparisons may provide information that can improve management of
      S. macrophylla and M. azedarach plantations in tropical regions. RESULTS: Both
      species exhibited a midday depression in leaf photosynthesis regardless of the
      season. The net photosynthetic rate (P N), stomatal conductance (g s), and
      transpiration rate (E) in the dry season all significantly decreased in both tree
      species. In addition, M. azedarach used water more efficiently than did S.
      macrophylla during the dry season, but S. macrophylla had higher P N compared
      with that in M. azedarach during the wet season. Temperature and vapor pressure
      deficit influenced P N variation in S. macrophylla and M. azedarach,
      respectively. Our data suggested that the P N and g s of M. azedarach, but not of
      S. macrophylla, were linearly correlated during the dry season. The reduction of
      the leaf area was more sever in M. azedarach than in S. macrophylla, thus
      preventing water loss more efficiently. CONCLUSIONS: M. azedarach adapted to
      drought by reducing total leaf area and maintaining higher P N, g s, E, and WUE
      compared with those measured in S. macrophylla during the dry season. M.
      azedarach is more drought adaptation and more suitable for both humid and semi
      humid areas than S. macrophylla, whereas the latter should be limited to more
      humid areas.

PMID- 29198039
TI  - Brief Report: Screening Adults with Autism Spectrum Disorder for Anxiety and
      Depression.
AB  - Although depression and anxiety are the most common comorbidities in individuals
      with Autism Spectrum Disorder (ASD), descriptive data for their prevalence among
      autistic adults are limited. This study provides descriptive data for a cohort of
      155 autistic adults (mean age = 27.1 years, SD = 11.9) of average IQ on the short
      form version of the Depression Anxiety Stress Scales and the Mini Social Phobia
      Inventory. Also included were 79 non-ASD participants (mean age = 26.2, SD =
      10.2) who completed the mini-SPIN. A substantial percentage (39-46%) of autistic
      adults scored within the 'Moderate' to 'Extremely Severe' range on the DASS-21.
      The DASS-21 would be a valuable rapid screening device for these comorbid
      conditions in autistic adults.

PMID- 29198040
TI  - Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum
      Disorders: Behavioral Correlates and Clinical Implications.
AB  - In a sample of 37 adolescents and young adults with autism spectrum disorder
      (ASD) and 35 typically-developing controls (TDC), we investigated sensory
      symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz
      with the frequency and duration oddball paradigms of event-related potentials.
      Results showed that compared to TDC, ASD participants reported more sensory
      symptoms, and presented a shorter P3a peak latency in the duration paradigm,
      which was correlated with more social awareness deficits. In the frequency
      paradigm, P3a parameters were correlated with sensation avoiding and attention
      characteristics of ASD. Our findings suggest that sensory abnormality in ASD may
      extend into adolescence and young adulthood. P3a latency might be a potential
      neurophysiological marker for ASD.

PMID- 29198041
TI  - Ethical considerations on novel neuronal interfaces.
AB  - Wireless powered implants, each smaller than a grain of rice, have the potential
      to scan and stimulate brain cells. Further research may lead to next-generation
      brain-machine interfaces for controlling prosthetics, exoskeletons, and robots,
      as well as "electroceuticals" to treat disorders of the brain and body. In
      conditions that can be particularly alleviated with brain stimulation, the use of
      such mini devices may pose certain challenges. Health professionals are becoming
      increasingly more accountable in decision-making processes that have impacts on
      the life quality of individuals. It is possible to transmit such stimulation
      using remote control principles. Perhaps, the most important concern regarding
      the use of these devices termed as "neural dust" is represented by the
      possibility of controlling affection and other mental functions via waves
      reaching the brain using more advanced versions of such devices. This will not
      only violate the respect for authority principle of ethics, but also medical
      ethics, and may potentially lead to certain incidents of varying vehemence that
      may be considered illegal. Therefore, a sound knowledge and implementation of
      ethical principles is becoming a more important issue on the part of healthcare
      professionals. In both the ethical decision-making process and in ethical
      conflicts, it may be useful to re-appraise the principles of medical ethics. In
      this article, the ethical considerations of these devices are discussed.

PMID- 29198042
TI  - Seizure as the unique clinical manifestation of cerebral metastases in a 27-year
      old man with non-small cell lung cancer.

PMID- 29198043
TI  - The diagnosis of dementias: a practical tool not to miss rare causes.
AB  - Dementia represents one of the most diffuse disorders of our Era. Alzheimer's
      disease is the principle cause of dementia worldwide. Metabolic, infectious,
      autoimmune, inflammatory, and genetic dementias represent a not negligible number
      of disorders, with increasing numbers in younger subjects. Due to the
      heterogeneity of patients and disorders, the diagnosis of dementia is
      challenging. In the present article, we propose a practical diagnostic approach
      following the two-step investigation procedure. The first step includes basic
      blood tests and brain neuroimaging, performed on all patients. After this first
      line investigation, it is then possible to rule out metabolic causes of dementia
      and to identify three main subgroups in dementia: predominant gray matter
      atrophy, white matter disease, basal ganglia pathologies. The predominant gray
      matter atrophy subgroup includes neurodegenerative causes of dementia and some
      lysosomal storage disorders. The white matter subgroup indicates a comprehensive
      list of vascular dementia causes, mitochondrial diseases, and leukodystrophies.
      Whereas, the basal ganglia alterations are due to metal accumulation pathologies,
      such as iron, copper, or calcium. Each category has specific clinical hallmarks,
      accurately reported in the article, and requires specific second-line
      investigation. Thus, we indicate the distinct second diagnostic step of each
      disease. The proposed diagnostic flow-chart follows the clinical reasoning and
      helps clinicians through the differential diagnosis of dementia.

PMID- 29198044
TI  - Lifestyle factors and social ties associated with the frequency of laughter after
      the Great East Japan Earthquake: Fukushima Health Management Survey.
AB  - PURPOSE: Although mental health problems such as depression after disasters have
      been reported, positive psychological factors after disasters have not been
      examined. Recently, the importance of positive affect to our health has been
      recognised. We therefore investigated the frequency of laughter and its related
      factors among residents of evacuation zones after the Great East Japan Earthquake
      of 2011. METHODS: In a cross-sectional study on 52,320 participants aged 20 years
      and older who were included in the Fukushima Health Management Survey in Japan's
      fiscal year 2012, associations of the frequency of laughter with changes in
      lifestyle after the disaster, such as a changed work situation, the number of
      family members, and the number of address changes, and other sociodemographic,
      psychological, and lifestyle factors were examined using logistic regression
      analysis. The frequency of laughter was assessed using a single-item question:
      "How often do you laugh out loud?" RESULTS: The proportion of those who laugh
      almost every day was 27.1%. Multivariable models adjusted for sociodemographic,
      psychological, and lifestyle factors demonstrated that an increase in the number
      of family members and fewer changes of address were significantly associated with
      a high frequency of laughter. Mental health, regular exercise, and participation
      in recreational activities were also associated with a high frequency of
      laughter. CONCLUSION: Changes in lifestyle factors after the disaster were
      associated with the frequency of laughter in the evacuation zone. Future
      longitudinal studies are needed to examine what factors can increase the
      frequency of laughter.

PMID- 29198045
TI  - Physical and mental health status and their correlations among older wheelchair
      users with dementia in long-term care facilities.
AB  - PURPOSE: To investigate the physical health (daily functioning and functional
      fitness) and mental health (depression and behavioral dysfunction) of older
      wheelchair users with dementia in long-term care facilities, examine the
      correlations between physical and mental health, and identify the independent
      variables of their daily functioning. METHODS: A descriptive correlational method
      was adopted, which was conducted in six long-term care facilities in three
      cities, south Taiwan. Participants comprised 98 older wheelchair users with
      dementia. Data were collected using structured questionnaires (Mini-Mental State
      Examination, Barthel Index, Cornell Scale for Depression in Dementia, and Clifton
      Assessment Procedures for the Elderly Behavior Rating Scale) and from functional
      fitness testing (cardiopulmonary functioning, body flexibility, joint mobility,
      and muscle strength and endurance). RESULTS: Older adults with dementia who had
      high depression scores were likely to have more behavioral dysfunctions, poorer
      performance in shoulder flexion and abduction, and lower upper limb muscle
      strength and endurance. More behavioral dysfunctions were associated with poorer
      daily functioning, lung capacity, body flexibility, shoulder flexion, and upper
      limb muscle strength and endurance. Those with better lung capacity, body
      flexibility, upper limb muscle strength, and endurance were likely to have high
      daily functioning scores (all p < .05). The key independent variables associated
      with daily functioning were behavioral dysfunction, lower body flexibility, and
      lung capacity, which together explained 59.3% of the total variance. CONCLUSIONS:
      Further research should develop appropriate activity-based intervention programs
      for older wheelchair users with dementia to delay their deterioration and promote
      their physical and mental health.

PMID- 29198046
TI  - Is treatment of geriatric hip fracture patients cost-covering? Results of a
      prospective study conducted at a German University Hospital.
AB  - INTRODUCTION: Hip fractures have increased medical and socio-economic importance
      due to demographic transition. Information concerning direct treatment costs and
      their reimbursement in Germany is lacking. MATERIALS AND METHODS: Four hundred
      two hip fracture patients older than 60 years of age were observed prospectively
      at a German University Hospital. Treatment costs were determined with up to 196
      cost factors and compared to the reimbursement. Finally, statistical analysis was
      performed to identify clinical parameters influencing the cost-reimbursement
      relation. RESULTS: Treatment costs were 8853 ? (95% CI 8297-9410 ?), while
      reimbursement was 8196 ? (95% CI 7707-8772 ?), resulting in a deficit of 657 ?
      (95% CI 143-1117 ?). Bivariate analysis showed that the cost-reimbursement
      relation was negatively influenced mainly by higher age, higher ASA score,
      readmission to the intensive care unit (ICU) and red blood cell transfusion.
      Adjusted for other parameters, readmission to the ICU was a significant negative
      predictor (- 2669 ?; 95% CI - 4070 to - 1268 ?; p < 0.001), while age of 60-75
      years was a positive predictor for the cost-reimbursement relation (1373 ?; 95%
      CI 265-2480 ?; p = 0.015). CONCLUSIONS: Treatment of geriatric hip fracture
      patients in a university hospital in Germany does not seem to be cost-covering.
      Adjustment of the reimbursement for treatment of complex hip fracture patients
      should be considered.

PMID- 29198047
TI  - Medial meniscus grafting restores normal tibiofemoral contact pressures.
AB  - BACKGROUND: Tissue excision in the setting of a meniscal tear has been shown to
      dramatically increase peak contact stresses in the affected tibiofemoral joint
      compartment, leading to the development of degenerative changes and
      osteoarthritis. PURPOSE/HYPOTHESIS: The current in vitro study utilized a porcine
      model to evaluate the effectiveness of segmental medial meniscal grafting
      following partial meniscectomy. The study hypothesis was that the procedure would
      normalize medial tibofemoral joint compartment pressure magnitudes, areas, and
      locations relative to an intact meniscus. STUDY DESIGN: Controlled laboratory
      study. METHODS: Using pressure film, medial tibiofemoral joint compartment peak,
      and mean pressure magnitudes, peak pressure location and peak pressure area were
      determined using 12 potted, fresh frozen, porcine knee specimens. Data were
      collected at three different knee flexion angles (90 degrees , 45 degrees , and 0
      degrees ) for three conditions: intact medial meniscus, following resection of
      the central third of the medial meniscus, and following segmental medial meniscal
      grafting. For each condition, the potted femur was positioned horizontally in a
      bench vise clamp, while a 20 pound (88.96 N) axial compression force was manually
      applied for a 60 s duration by the primary investigator through the base of the
      potted tibia using a digital force gauge. RESULTS: Loss of the central 1/3 of the
      medial meniscus resulted in significant increases in the mean and peak pressures
      of the medial tibiofemoral joint compartment and decreased peak pressure area.
      Segmental meniscal grafting of the central third defect closely recreated the
      contact pressures and loading areas of the native, intact medial meniscus.
      CONCLUSION: From a static, time zero biomechanical perspective, segmental medial
      meniscus grafting of a partially meniscectomized knee restored mean pressure,
      peak pressure, and mean peak contact pressure areas of the medial tibiofemoral
      joint compartment back to levels observed in the intact medial meniscus at
      different knee flexion angles. In-vivo analysis under dynamic conditions is
      necessary to verify the healing efficacy and ability of the healed segmental
      medial meniscal allograft to provide long-term knee joint homeostasis when
      confronted with dynamic shear, rotatory, and combined, higher magnitude
      physiologic loading forces.

PMID- 29198048
TI  - Magnesium in Breast Cancer: What Is Its Influence on the Progression of This
      Disease?
AB  - Breast cancer is a disease of high mortality, characterized by the progressive
      accumulation of mutations that contribute to the uncontrolled development of
      breast tissue cells. Literature shows that disturbances in mineral homeostasis,
      such as magnesium, may interfere with tumor progression. The objective of this
      study is to provide updated information about magnesium's role in the
      pathogenesis of breast cancer. A review of literature was carried out from a
      search for articles in the PubMed and CAPES Periodicals databases published
      between 1995 and 2016 with the cross-references of the descriptors "magnesium,"
      "breast neoplasms," and "oxidative stress" and the corresponding words in
      Portuguese. We included studies on the metabolism and bioavailability of
      magnesium and studies related to breast cancer and excluded articles in which
      only the abstract was available, dissertations, theses, articles involving
      adjuvant and/or neoadjuvant therapies, and supplementation of minerals in breast
      cancer patients. Magnesium is a mineral that participates in the metabolism of
      various nutrients and nucleic acids. In the presence of breast cancer, neoplastic
      cells increase the expression of magnesium transport channels, which raises the
      intracellular concentration of the mineral, contributing to tumor growth through
      its function of increasing energy demand. The data obtained in this review
      illustrates the influence of magnesium on the progression of breast cancer.
      However, the existing data are scarce and inconsistent, which demonstrates a need
      for further studies on the subject with a goal to have better control of the
      disease.

PMID- 29198049
TI  - Voces de la frontera/Voices from the Border: Using Case Studies of Pregnancy,
      Birth and Parenting along the U.S.-Mexico Border to Identify Shared Measures of
      Success.
AB  - Purpose This research analyzes the cases of five women living along the U.S.
      Mexico border who overcame challenges during pregnancy or parenting with the
      support of a federally funded Healthy Start program, designed to eliminate
      disparities in perinatal health in disadvantaged communities with the poorest
      birth outcomes. Study objectives were to: (1) identify common factors that affect
      healthy maternal and child outcomes for Healthy Start participants; and (2)
      identify a shared definition of what success looks like for Healthy Start
      participants and opportunities for further study. Description Five border Healthy
      Start sites (CA, AZ, NM, and TX) contributed case stories from participants who
      had overcome access barriers to achieve positive pregnancy, birth or parenting
      outcomes. Case studies were collected using review of successful participant
      cases and non-structured interviews by Healthy Start staff, and analyzed using
      participatory methods and thematic analysis. Assessment Common barriers were:
      lack of insurance; isolation or unsupportive family relationships; timidness and
      lack of self-advocacy. Healthy Start programs have been successful in securing
      supportive relationships through the community health worker model; reducing
      isolation; obtaining insurance access and a medical home; building self-advocacy
      skills; and supporting participants to pursue their goals. Conclusion Identified
      barriers are in line with available literature on health care access and provide
      a U.S.-Mexico border-specific view. The Healthy Start model is effective at
      helping women to overcome barriers. Learning from this research may contribute to
      development of shared measures for more impactful evaluation of Healthy Start and
      similar programs.

PMID- 29198050
TI  - Oral Health Coverage Options for Pregnant Adults and Adolescents.
AB  - Oral health care is a necessary and critical component of health care for
      pregnant women, but its importance is often overlooked by clinicians. Pregnant
      women who are low-income also find it particularly difficult to access care. This
      analytic essay summarizes oral health coverage for pregnant women under various
      types of health insurance coverage, including Medicaid, the Children's Health
      Insurance Program, and coverage options available under the Affordable Care Act.
      We hope this information will help clinicians better understand the importance of
      oral health care during pregnancy and the range of coverage options that may be
      available to their patients.

PMID- 29198051
TI  - Doula Services Within a Healthy Start Program: Increasing Access for an
      Underserved Population.
AB  - PURPOSE: Women of color in the United States, particularly in high-poverty
      neighborhoods, experience high rates of poor birth outcomes, including cesarean
      section, preterm birth, low birthweight, and infant mortality. Doula care has
      been linked to improvements in many perinatal outcomes, but women of color and
      low-income women often face barriers in accessing doula support. DESCRIPTION: To
      address this issue, the New York City Department of Health and Mental Hygiene's
      Healthy Start Brooklyn introduced the By My Side Birth Support Program in 2010.
      The goal was to complement other maternal home-visiting programs by providing
      doula support during labor and birth, along with prenatal and postpartum visits.
      Between 2010 and 2015, 489 infants were born to women enrolled in the program.
      ASSESSMENT: Data indicate that By My Side is a promising model of support for
      Healthy Start projects nationwide. Compared to the project area, program
      participants had lower rates of preterm birth (6.3 vs. 12.4%, p < 0.001) and low
      birthweight (6.5 vs. 11.1%, p = 0.001); however, rates of cesarean birth did not
      differ significantly (33.5 vs. 36.9%, p = 0.122). Further research is needed to
      explore possible reasons for this finding, and to examine the influence of doula
      support on birth outcomes among populations with high rates of chronic disease
      and stressors such as poverty, racism, and exposure to violence. However,
      feedback from participants indicates that doula support is highly valued and
      helps give women a voice in consequential childbirth decisions. CONCLUSION:
      Available evidence suggests that doula services may be an important component of
      an effort to address birth inequities.

PMID- 29198052
TI  - Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated
      with an increased local failure rate following conventional therapy.
AB  - Studies on melanoma brain metastases (MBM) with regard to mutational status are
      lacking. We investigated the outcomes of MBM in molecularly characterized
      patients for BRAF and NRAS mutations receiving conventional treatment. We
      investigated associations between outcomes [competing risk of local and distant
      brain failure (LF, DF) and overall survival (OS)] and clinical/pathological
      features of patients with known mutation status following initial treatment of
      MBM. Competing risk analysis was performed using the methods of Fine and Gray. We
      identified 235 patients with MBM diagnosed from 2005 to 2011. Mutation prevalence
      was BRAF non-V600K 98 (42%), BRAF V600K 34 (14%), NRAS 43 (18%), and wild-type
      for both genes (WT) 60 (26%) patients. Six month cumulative incidence LF rates
      were 3% for combined SRS or surgery with adjuvant radiation, 18% for surgery, 18%
      for SRS, 60% for WBRT, and 67% for systemic therapy. On multivariate analysis,
      only mutation status and initial treatment type were found to be independent
      predictors of local control. As compared to WT, NRAS (HR 2.58, 95% CI 1.18-5.67,
      p = 0.02) and BRAF V600K (HR 2.83, 95% CI 1.23-6.47, p = 0.01) mutational status
      were statistically significant while BRAF non-V600K status was not statistically
      significant (p = 0.23). Mutation status was not associated with DF or OS. BRAF
      V600K and NRAS mutation status predict increased LF following conventional
      treatments for MBM. These data can inform the design and interpretation of future
      MBM trials.

PMID- 29198053
TI  - Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test
      new therapies in some patients?
AB  - Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient
      treatments. They can be developed at relapse or at diagnosis, but therefore they
      must be combined with radiotherapy. Survival of children after recurrence and its
      predictors were studied to inform the possibility to design early phase clinical
      trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and
      2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We
      defined as long survivors' patients who survived more than 3 months after relapse
      which corresponds to the minimal life expectancy requested for phase I/II trials.
      Factors influencing post-relapse survival were accordingly compared between short
      and long-term survivors after relapse. Fifty-seven percent of patients were
      considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50%
      at relapse. Patients who became steroids-independent after initial treatment for
      at least 2 months had better survival after relapse (3.7 versus 2.6 months, p =
      0.001). LPS above 50% at relapse was correlated with better survival after
      relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived
      longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a
      second radiotherapy at the time of relapse had an improved survival (7.5 versus 4
      months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS
      predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not
      improve prediction. Survival of many DIPG patients after relapse over 3 months
      would make possible to propose specific trials for this condition. Steroid
      independence, H3 mutation status and LPS should be considered to predict
      eligibility.

PMID- 29198054
TI  - A case of unusually long survival after leptomeningeal carcinomatosis diagnosis.

PMID- 29198055
TI  - Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+
      locally advanced or metastatic breast cancer resistant to trastuzumab-based
      therapy.
AB  - PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal
      growth factor receptor-2- (HER2)-positive advanced breast cancer defined the
      recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg
      weekly trastuzumab, and reported preliminary signs of clinical activity. Here we
      present results from the Phase II portion. METHODS: Patients with trastuzumab
      resistant, HER2-positive advanced breast cancer received buparlisib plus
      trastuzumab. Study endpoints included safety/tolerability and antitumour
      activity. The study was extended to include a Phase Ib dose-escalation phase, in
      which patients with progressive brain metastases also received capecitabine.
      RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and
      trastuzumab, the most common (>= 30%) all-grade adverse events (AEs) were
      diarrhoea (54%), nausea (48%), decreased appetite, increased alanine
      aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue,
      rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved
      complete response and four (8%) patients had confirmed partial responses [PR;
      including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway
      activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint
      (ORR >= 25%) was therefore not met. In the Phase Ib portion, all patients with
      measurable brain lesions at baseline showed tumour shrinkage to some degree; due
      to low enrollment, maximum tolerated dose of buparlisib in combination with
      trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus
      trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety
      profile but limited efficacy in patients with heavily pretreated, trastuzumab
      resistant HER2-positive breast cancer, and in patients with progressive brain
      metastases also receiving capecitabine.

PMID- 29198056
TI  - Clinical impact of recovery room on post-operative walking performance in elderly
      patients submitted to hip surgery: a real-world analysis.
AB  - BACKGROUND: Strategies aimed at favouring functional recovery after surgery for
      hip fracture may be of clinical importance. AIMS: To test the clinical utility of
      a recovery room (RR) in terms of postoperative walking performance in an elderly
      population submitted to hip fracture surgery. METHODS: Postoperative walking
      performance at rollator was assessed in 242 consecutive orthogeriatric patients
      able to follow the institutional physiotherapy protocol starting on day 1 after
      hip surgery. Group 1 (n = 186, age 86.0 +/- 9.3 years, 24.7% male) was admitted
      to the RR for postoperative monitoring, whereas Group 2 (n = 56, age 85.2 +/- 5.7
      years, 23.2% male) was directly admitted to the ward. The best performance
      observed during the first three postoperative days was considered. RESULTS: Group
      1 showed a better walking performance than Group 2, with a 50% lower probability
      of walking < 5 m (relative risk 0.51, p = 0.0005) and a two-fold higher
      probability of walking > 10 m (relative risk 2.10, p = 0.0005). Multivariable
      analysis confirmed a favourable independent effect of the RR stay on walking
      performance (beta = 0.205, p = 0.005). DISCUSSION: Admission to the RR in elderly
      patients submitted to hip fracture surgery could have an independent beneficial
      effect on postoperative walking functional recovery. This beneficial effect could
      probably depend on the possibility of ensuring a more rapid management of
      postoperative issues CONCLUSIONS: These findings support the clinical utility of
      a RR implementation in facilities where hip surgery in elderly subjects is
      routinely performed.

PMID- 29198057
TI  - Acceptability of physical activity monitoring in older adults undergoing
      inpatient rehabilitation.
AB  - BACKGROUND: There is little research into interventions to increase activity
      levels of hospitalised older adults. AIMS: To assess the feasibility of using a
      physical activity monitor (PAL2) in hospitalized older adults and the effect of
      group exercise on activity levels. METHODS: Participants were hospitalized,
      ambulant adults >= 65 years randomized to individual physical therapy alone or
      combined with a high intensity exercise group and wore the PAL2 for five
      consecutive days. RESULTS: Only 33% of eligible participants agreed to
      participate with 19/30 (63%) complete data sets obtained; physical activity
      levels were low regardless of intervention. CONCLUSION: Acceptability of physical
      activity monitoring in hospitalized older adults was low and physical activity
      levels of those monitored was low across groups. To improve monitor compliance,
      future studies may consider excluding patients with specific comorbidities that
      impact on wear time, or selection of an alternative monitor.

PMID- 29198058
TI  - Analyzing gait variability and dual-task interference in patients with
      Parkinson's disease and freezing by means of the word-color Stroop test.
AB  - The ability to carry out two tasks at once is critical to effective functioning
      in the real world and deficits are termed Dual-task interference or effect-DTE.
      DTE substantially compromised the gait of subjects with Parkinson's disease and
      freezing of gait (PD + FOG), leading to exaggerated slowing, increasing gait
      dysrhythmicity, and inducing FOG episodes. This study aimed to investigate the
      DTE in gait variability of subjects with PD and freezing of gait (PD + FOG).
      Thirty-three patients with PD + FOG and 14 healthy individuals (REFERENCE) took
      part at this study. Two gait conditions were analyzed: usual walking (single
      task) and walking while taking the word-color Stroop test (dual task). The
      computed variables were as follows: gait velocity, step length, step timing, gait
      asymmetry, variability measures and DTE of each variable. The PD + FOG group has
      presented negative DTE values for all analyzed variables, indicating dual task
      cost. The REFERENCE group has presented dual-task benefits for step length
      standard deviation and step time. Differences between both groups and conditions
      were found for all variables, except for step time. Taking the word-color Stroop
      test while walking led to a larger dual-task cost in subjects with PD + FOG.

PMID- 29198059
TI  - Metabolic effects of physiological levels of caffeine in myotubes.
AB  - Caffeine has been shown to stimulate multiple major regulators of cell energetics
      including AMP-activated protein kinase (AMPK) and Ca2+/calmodulin-dependent
      protein kinase II (CaMKII). Additionally, caffeine induces peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and
      mitochondrial biogenesis. While caffeine enhances oxidative metabolism,
      experimental concentrations often exceed physiologically attainable
      concentrations through diet. This work measured the effects of low-level caffeine
      on cellular metabolism and gene expression in myotubes, as well as the dependence
      of caffeine's effects on the nuclear receptor peroxisome proliferator-activated
      receptor beta/delta (PPARbeta/delta). C2C12 myotubes were treated with various
      doses of caffeine for up to 24 h. Gene and protein expression were measured via
      qRT-PCR and Western blot, respectively. Cellular metabolism was determined via
      oxygen consumption and extracellular acidification rate. Caffeine significantly
      induced regulators of mitochondrial biogenesis and oxidative metabolism.
      Mitochondrial staining was suppressed in PPARbeta/delta-inhibited cells which was
      rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed
      elevated peak oxidative metabolism which was partially abolished following
      PPARbeta/delta inhibition. Similar to past observations, glucose uptake and GLUT4
      content were elevated in caffeine-treated cells, however, glycolytic metabolism
      was unaltered following caffeine treatment. Physiological levels of caffeine
      appear to enhance cell metabolism through mechanisms partially dependent on
      PPARbeta/delta.

PMID- 29198060
TI  - No major role of norepinephrine transporter gene variations in the
      cardiostimulant effects of MDMA.
AB  - PURPOSE: Methylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and
      frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and
      subjective stimulant effects that were shown to partially depend on the
      norepinephrine transporter (NET)-mediated release of norepinephrine and
      stimulation of alpha1-adrenergic receptors. Genetic variants, such as single
      nucleotide polymorphisms (SNPs), of the NET gene (SLC6A2) may explain
      interindividual differences in the acute stimulant-type responses to MDMA in
      humans. METHODS: We characterized the effects of common genetic variants of the
      SLC6A2 gene (rs168924, rs47958, rs1861647, rs2242446, and rs36029) on
      cardiovascular and subjective stimulation after MDMA administration in 124
      healthy subjects in a pooled analysis of eight double-blind, placebo-controlled
      studies. RESULTS: Carriers of the GG genotype of the SLC6A2 rs1861647 SNP
      presented higher elevations of heart rate and rate-pressure product after MDMA
      than subjects with one or no G alleles. Subjects with a C allele in the SLC6A2
      rs2242446 SNP presented higher elevations of the heart rate after MDMA
      administration compared with the TT genotype. Subjects with the AA genotype of
      the SLC6A2 rs36029 SNP presented higher elevations of mean arterial pressure and
      rate pressure product after MDMA administration than carriers of the G allele.
      The SLC6A2 rs168924 and rs47958 SNPs did not alter the response to MDMA.
      CONCLUSIONS: Genetic polymorphisms of the SLC6A2 gene weakly moderated the acute
      cardiovascular response to MDMA in controlled studies and may play a minor role
      in adverse cardiovascular events when MDMA is used recreationally.

PMID- 29198061
TI  - Development and pilot testing of PHARAO-a decision support system for
      pharmacological risk assessment in the elderly.
AB  - PURPOSE: The aims of this study are to describe the development of PHARAO
      (Pharmacological Risk Assessment Online), a decision support system providing a
      risk profile for adverse events, associated with combined effects of multiple
      medicines, and to present data from a pilot study, testing the use,
      functionality, and acceptance of the PHARAO system in a clinical setting.
      METHODS: About 1400 substances were scored in relation to their risk to cause any
      of nine common and/or serious adverse effects. Algorithms for each adverse effect
      score were developed to create individual risk profiles from the patient's list
      of medication. The system was tested and integrated to the electronic medical
      record, during a 4-month period in two geriatric wards and three primary
      healthcare centers, and a questionnaire was answered by the users before and
      after the test period. RESULTS: A total of 732 substances were tagged with one or
      more of the nine risks, most commonly with the risk of sedation or seizures.
      During the pilot, the system was used 933 times in 871 patients. The most common
      signals generated by PHARAO in these patients were related to the risks of
      constipation, sedation, and bleeding. A majority of responders considered PHARAO
      easy to use and that it gives useful support in performing medication reviews.
      CONCLUSIONS: The PHARAO decision support system, designed as a complement to a
      database on drug-drug interactions used nationally, worked as intended and was
      appreciated by the users during a 4-month test period. Integration aspects need
      to be improved to minimize unnecessary signaling.

PMID- 29198062
TI  - An evaluation of four modes of low-dose anticoagulation during intermittent
      haemodialysis.
AB  - INTRODUCTION: Intensive care participants that need dialysis frequently suffer
      from increased risk of bleeding. Standard intermittent haemodialysis (SHD)
      includes anticoagulation to avoid clotting of the dialysis system. The aim of
      this study was to clarify which of four different low-dose anticoagulant modes
      was preferable in reducing the exposure to i.v. unfractionated heparin (heparin)
      and maintaining patency of the dialysis circuit. METHODS: Twenty-three patients
      on SHD were included to perform haemodialysis with four modes of low-dose
      anticoagulation. For comparative analyses, patients served as their own control.
      Haemodialysis with a single bolus of tinzaparin at the start was compared to
      haemodialysis initiated without i.v. heparin but priming with (1) heparin in
      saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in
      combination with a citrate-containing dialysate (HAC), (4) saline and usinga
      heparin-coated filters (Evodial(r)). The priming fluid was discarded before
      dialysis started. Blood samples were collected at 0, 30 and 180 min during
      haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed
      during the modes to avoid interruption by clotting. FINDINGS: The mean activated
      partial thromboplastin (APTT) time as well as the doses of anticoagulation
      administered was highest with SHD and least with HAC and Evodial(r). Mode H
      versus SHD had the highest rate of prematurely interrupted dialyses (33%, p =
      0.008). The urea reduction rate was less with Evodial(r) vs. SHD (p < 0.01). One
      hypersensitivity reaction occurred with Evodial(r). Changes in blood cell
      concentrations and triglycerides differed between the modes. DISCUSSION: If
      intermittent haemodialysis is necessary in patients at risk of bleeding,
      anticoagulation using HAC and Evodial(r) appeared most preferable with least
      administration of heparin, lowest APTT increase and lowest risk for prematurely
      clotted dialyzers in contrast to the least plausible H mode.

PMID- 29198063
TI  - Baclofen in gamma-hydroxybutyrate withdrawal: patterns of use and online
      availability.
AB  - PURPOSE: Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition
      that does not always respond to standard treatment with benzodiazepines. Baclofen
      has potential utility as a pharmacological adjunct and anecdotal reports suggest
      that it is being used by drug users to self-manage GHB withdrawal symptoms. Here,
      we investigate current patterns of use and the online availably of baclofen.
      METHODS: Data triangulation techniques were applied to published scientific
      literature and publicly accessible Internet resources (grey literature) to assess
      the use of baclofen in GHB withdrawal. An Internet snapshot survey was performed
      to identify the availability of baclofen for online purchase and the compliance
      of retailers with the UK regulations. Data were collected according to pre
      defined criteria. RESULTS: A total of 37 cases of baclofen use in GHB withdrawal
      were identified in the scientific literature, as well as 51 relevant discussion
      threads across eight Internet forums in the grey literature. Baclofen was
      available to purchase from 38 online pharmacies, of which only one conformed to
      the UK regulations. CONCLUSIONS: There is limited published evidence on the use
      of baclofen in GHB withdrawal, but both scientific and grey literature suggests
      clinical utility. Online pharmacies are readily offering prescription-only
      medication without prescription and due to inadequate regulation, pose a danger
      to the public.

PMID- 29198064
TI  - Claiming desmopressin therapeutic equivalence in children requires pediatric
      data: a population PKPD analysis.
AB  - PURPOSE: For a new formulation of a drug, only pharmacokinetic bioequivalence
      with the original formulation has to be demonstrated in healthy, young adults.
      However, "children are not small adults," and to guarantee a safe and effective
      treatment, age-adapted drug development is required. Desmopressin, a vasopressin
      analogue prescribed for nocturnal enuresis in children, was studied as an example
      formulation first developed in adults and then extrapolated to a pediatric
      indication. METHODS: Population pharmacokinetic and pharmacodynamic modeling was
      used to analyze previously published desmopressin data of 18 children suffering
      from nocturnal enuresis. The main objective was the comparison of the therapeutic
      equivalence of two desmopressin formulations: tablet and lyophilisate. The
      measurements for pharmacokinetics and pharmacodynamics were respectively plasma
      desmopressin concentration and urine osmolality and diuresis. RESULTS: The half
      maximal inhibitory concentration for inhibition of urine production was 0.7 pg/mL
      lower for the lyophilisate than for the tablet. The effect of formulation on the
      half maximal inhibitory concentration seems to suggest that the 120-MUg
      lyophilisate has a more pronounced effect on the urine volume and osmolality than
      the 200-MUg tablet, even when the same exposure is achieved. CONCLUSIONS: A new
      indirect response model for desmopressin was constructed and validated, using a
      previously built pharmacokinetic model and additional pharmacodynamic data. In
      order to draw solid conclusions regarding the efficacy and safety of desmopressin
      in children, pharmacokinetics and pharmacodynamics data should be analyzed
      together. This study adds proof to potential differences in pediatric and adult
      pharmacokinetic and pharmacodynamic properties of desmopressin and exemplifies
      the need for pediatric clinical trials, not only for every new drug but also for
      every new formulation.

PMID- 29198066
TI  - Agelamasines A and B, diterpene alkaloids from an Okinawan marine sponge Agelas
      sp.
AB  - Two new diterpene alkaloids having an N-methyladenine moiety, agelamasines A (1)
      and B (2), were isolated from an Okinawan marine sponge Agelas sp. The structures
      of 1 and 2 were elucidated on the basis of spectroscopic analyses. Agelamasine A
      (1) is the first diterpene alkaloid with a rearranged (4 -> 2)-abeo-clerodane
      skeleton from a marine source, while agelamasine B (2) is a clerodane diterpene
      alkaloid.

PMID- 29198065
TI  - Pretargeting of internalizing trastuzumab and cetuximab with a 18F-tetrazine
      tracer in xenograft models.
AB  - BACKGROUND: Pretargeting-based approaches are being investigated for
      radioimmunoimaging and therapy applications to reduce the effective radiation
      burden to the patient. To date, only a few studies have used short-lived
      radioisotopes for pretargeting of antibodies, and such examples with
      internalizing antibodies are even rarer. Herein, we have investigated
      pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for
      tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab
      and trastuzumab. RESULTS: Bioorthogonal reaction between tetrazine and trans
      cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a
      fluorine-18 (t 1/2 = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab
      was administered 24, 48, or 72 h prior to the injection of tracer to A431 or BT
      474 tumour-bearing mice, respectively. With cetuximab, the highest tumour-to
      blood ratios were achieved when the lag time between antibody and tracer
      injections was 72 h. With trastuzumab, no difference was observed between
      different lag times. For both antibodies, the tumour could be clearly visualized
      in the PET images with the highest tumour uptake of 3.7 +/- 0.1%ID/g for
      cetuximab and 1.5 +/- 0.1%ID/g for trastuzumab as quantified by ex vivo
      biodistribution. In vivo IEDDA reaction was observed in the blood for both
      antibodies, but with trastuzumab, this was to a much lower degree than with
      cetuximab. CONCLUSIONS: We could successfully visualize the tumours by using
      cetuximab and trastuzumab in pretargeted PET imaging despite the challenging
      circumstances where the antibody is internalized and there is still some unbound
      antibody circulating in the blood flow. This clearly demonstrates the potential
      of a pretargeted approach for targeting internalizing antigens and warrants
      development of pharmacokinetic optimization of the biorthogonal reactants to this
      end.

PMID- 29198067
TI  - Bacterial perspectives on the dissemination of antibiotic resistance genes in
      domestic wastewater bio-treatment systems: beneficiary to victim.
AB  - Domestic wastes, ranging from sewage and sludge to municipal solid waste, are
      usually treated in bioprocessing systems. These systems are regarded as main
      conduits for the elevated levels of antibiotic resistance genes (ARGs) observed
      in the environment. This paper mainly reviews recent studies on the occurrence
      and dynamics of ARGs in wastewater bio-treatment systems and discusses the ins
      and outs of ARG dissemination from the perspective of the microbial community.
      Our analysis shows that concentration of antibiotics through adsorption to
      microbial aggregates triggers the bacteria to acquire ARGs, which can be
      facilitated by the presence of mobile genetic elements. Notably, the acquisition
      and flow of ARGs during the rapid dissemination process is directed towards and
      for the best interests of the microbial community as a whole, and is influenced
      by surrounding nutrient levels, toxicant types, and sensitivities of the species
      in the prevailing antibiotic-stressed conditions. Furthermore, our review argues
      that predation of ARG-carrying bacteria by bacteriophages does periodically
      enhance the accessibility of ARGs to bacteria, which indirectly facilitates the
      recruitment of ARGs into environmental microbial communities.

PMID- 29198068
TI  - Fibroblast growth factor 9 subfamily and the heart.
AB  - The fibroblast growth factor (FGF) 9 subfamily is a member of the FGF family,
      including FGF9, 16, and 20, potentially sharing similar biochemical functions due
      to their high degree of sequence homology. Unlike other secreted proteins which
      have a cleavable N-terminal secreted signal peptide, FGF9/16/20 have non-cleaved
      N-terminal signal peptides. As an intercellular signaling molecule, they are
      involved in a variety of complex responses in animal development. Cardiogenesis
      is controlled by many members of the transcription factor family. Evidence
      suggests that FGF signaling, including the FGF9 subfamily, has a pretty close
      association with these cardiac-specific genes. In addition, recent studies have
      shown that the FGF9 subfamily maintains functional adaptation and survival after
      myocardial infarction in adult myocardium. Since FGF9/16/20 are secreted
      proteins, their function characterization in cardiac regeneration can promote
      their potential to be developed for the treatment of cardioprotection and
      revascularization. Here, we conclude that the FGF9 subfamily roles in cardiac
      development and maintenance of postnatal cardiac homeostasis, especially cardiac
      function maturation and functional maintenance of the heart after injury.

PMID- 29198069
TI  - Does metformin exposure before ICU stay have any impact on patients' outcome? A
      retrospective cohort study of diabetic patients.
AB  - BACKGROUND: Impact of metformin exposure before ICU stay remains controversial.
      Metformin is thought to induce lactic acidosis and haemodynamic instability but
      may reduce ICU mortality. We evaluated its influence on outcome in diabetic
      patients admitted in the ICU and then compared two different populations based on
      the presence of septic shock. METHODS: We conducted a retrospective cohort study
      in a 24-bed French ICU between October 2010 and December 2013, including all ICU
      admitted diabetic patients. RESULTS: Among 635 diabetic patients admitted during
      the study period, 131 (21%) were admitted with septic shock. Multivariate
      analysis showed no difference in hospital mortality in all metformin users (OR
      0.75 [95% CI 0.44-1.28]; p = 0.29), except in the septic shock subgroup (OR 0.61;
      95% CI [0.37-0.99]; p = 0.04) despite higher vasopressor dosages in the first
      hours after shock onset. Blood lactate level was higher in metformin users than
      in non-metformin users in all patients (p < 0.001), in septic shock patients (p <
      0.001) and in patients without kidney injury (p < 0.001). Metformin users did not
      have more septic shock from unknown aetiology (p = 0.65) or unknown pathogen (p =
      0.99). CONCLUSIONS: Metformin use before admission to ICU did not affect in
      hospital mortality. However, for patients with septic shock, mortality was lower,
      despite worse clinical presentation on admission. Blood lactate levels were
      always higher with or without septic shock and indifferent of kidney function.

PMID- 29198071
TI  - A rare case of a molecular "adult-type" diffuse astrocytoma arising in a child.

PMID- 29198070
TI  - Sugar Detection Threshold After Laparoscopic Sleeve Gastrectomy in Adolescents.
AB  - INTRODUCTION: Obesity in young people is one of the most serious public health
      problems worldwide. Moreover, the mechanisms preventing obese adolescents from
      losing and maintaining weight loss have been elusive. Laparoscopic sleeve
      gastrectomy (LSG) is successful at achieving long-term weight loss in patients
      across all age groups, including children and adolescents. Anecdotal clinical
      observation as well as evidence in rodents suggests that LSG induces a shift in
      preference of sugary foods. However, it is not known whether this shift is due to
      a change in the threshold for gustatory detection of sucrose, or whether LSG
      induces behavioral change without affecting the gustatory threshold for sugar.
      AIMS: The objective of this study was to determine whether adolescents who
      undergo LSG experience a change in their threshold for detecting sweet taste.
      METHODS: We studied the sucrose detection threshold of 14 obese adolescents (age
      15.3 +/- 0.5 years, range 12-18) who underwent LSG 2 weeks before surgery and at
      12 and 52 weeks after surgery. Matched non-surgical subjects were tested on two
      occasions 12 weeks apart to control for potential learning of the test that may
      have confounded the results. Seven sucrose concentrations were used and were
      tested in eight blocks with each block consisting of a random seven sucrose and
      seven water stimuli. The subjects were asked to report whether the sample
      contained water or not after they tasted 15 ml of the fluid for 10 s. RESULTS:
      The bodyweight of the LSG group decreased from 136.7 +/- 5.4 to 109.6 +/- 5.1 and
      86.5 +/- 4.0 kg after 12 and 52 weeks, respectively (p < 0.001). There was no
      significant difference after surgery in taste detection threshold of patients
      after LSG (p = 0.60), and no difference was observed comparing the taste
      detection threshold of the LSG group with the non-surgical controls (p = 0.38).
      CONCLUSION: LSG did not affect the taste detection threshold for sucrose,
      suggesting that the shift in preference for sugary foods may be due to factors
      other than fundamental changes in taste sensitivity.

PMID- 29198072
TI  - PRES in the course of hemato-oncological treatment in children.
AB  - INTRODUCTION: Posterior reversible leukoencephalopathy syndrome (PRES) is a
      clinical syndrome of varying aetiologies, characterised by acute neurological
      symptoms of brain dysfunction with MRI abnormalities in posterior cerebral white
      and grey matter. In most cases, symptoms resolve without neurological
      consequences. AIM: The aim of this paper is the analysis of predisposing factors,
      clinical outcomes and radiological features of PRES in eight children with hemato
      oncological disease. MATERIAL AND METHODS: We analysed the medical records of
      eight hemato-oncological patients aged from 3.0 to 16.1 years. The mean of age at
      primary diagnosis was 8.5 years. RESULTS: All patients had both clinical and
      radiological PRES features. Seven out of eight underwent intensive chemotherapy
      regimens. Time elapsed from start of treatment to the occurrence of PRES ranged
      from 6 to 556 days. In one case, PRES occurred before chemotherapy and was the
      first symptom of cancer. Most (six of eight) patients had history of hypertension
      (> 95pc) and some (two of eight) occurred electrolyte imbalance-mainly
      hypomagnesaemia. Patients presented headache (seven of eight), disturbances of
      consciousness (six of eight), seizures (six of eight), visual changes (four of
      eight) and vomiting (three of eight). MRI demonstrated abnormalities in seven
      children: typical cerebral oedema in the white matter of the occipital to the
      parietal lobes. Most patient lesions in the MRI shrunk after 4 weeks, and
      clinical symptoms of PRES disappeared completely within a few hours to few days.
      CONCLUSION: PRES may complicate oncological treatment in children. Hypertension
      is the most important risk factor of PRES. PRES should be included in
      differential diagnosis in all patients with acute neurological symptoms.

PMID- 29198073
TI  - Apert syndrome: magnetic resonance imaging (MRI) of associated intracranial
      anomalies.
AB  - INTRODUCTION: Apert syndrome is one of the most common craniosynostosis syndrome
      caused by mutations in genes encoding fibroblast growth factor receptor 2
      (FGFR2). It is characterized by multisuture craniosynostosis, midfacial
      hypoplasia, abnormal skull base development and syndactyly of all extremities.
      Apert syndrome is associated with a wide array of central nervous system (CNS)
      anomalies, possibly the cause of the common occurrence of mental deficiency in
      patients with Apert syndrome. These CNS anomalies can be broadly classified into
      two groups; (1) those that are primary malformations and (2) those that occur
      secondary to osseous deformity/malformation. CONCLUSION: Familiarity with CNS
      anomalies associated with Apert syndrome is important to both clinicians and
      radiologist as it impacts on management and prognostication. Cognitive
      development of patients has been linked to associated CNS anomalies, timing of
      surgery and social aspects. These associated anomalies can be broadly classified
      into (1) those that are primary malformations and (2) those that occur secondary
      to osseous deformity/malformation, as illustrated in our review paper.

PMID- 29198075
TI  - Characteristics, management, and outcome of primary hyperparathyroidism at a
      single clinical center from 2005 to 2016.
AB  - : This study presents the clinical and biochemical profiles of patients with PHPT
      between 2005 and 2016 at our center. Most PHPT patients in China show symptomatic
      features. The number of symptomatic and asymptomatic patients increased during
      that time, and the number of individuals with parathyroid carcinoma is now
      increasing. INTRODUCTION: Over the last decade, the prevalence of primary
      hyperparathyroidism (PHPT) has increased sharply, and the number of individuals
      with parathyroid cancer is still trending upward. Little is known about the
      clinical outlook of the disease over the last decade in China. The aim of this
      study was to describe the clinical characteristics of PHPT patients at our center
      from January 2005 to December 2016. METHODS: Two hundred sixty patients with PHPT
      visiting Shanghai Jiao Tong University Affiliated Sixth People's Hospital were
      enrolled retrospectively. The clinical manifestations and biochemical
      abnormalities of these patients were analyzed. RESULTS: Among all patients, 73.1%
      had symptomatic PHPT, while the number of symptomatic and asymptomatic patients
      increased 1 to 2.5 times and 1.5 to 3 times, respectively, from 2005 to 2016.
      Bone pain and single adenoma were the most frequent signs and pathological
      results. The patients with parathyroid carcinoma over the last 5 years accounted
      for 90% (9/10) of all parathyroid carcinoma patients from 2005 to 2016, and
      parathyroid carcinoma patients had higher levels of serum calcium, parathyroid
      hormone (PTH), and serum creatinine (P < 0.05) than parathyroid hyperplasia and
      parathyroid adenoma patients. CONCLUSIONS: Most patients with PHPT in China still
      exhibit classic clinical and biochemical features. Both symptomatic and
      asymptomatic patients have increased over the last 12 years. Although the
      proportion of parathyroid carcinoma was small, a noticeable upward tendency was
      observed at our center.

PMID- 29198074
TI  - Comparison of muscle/lean mass measurement methods: correlation with functional
      and biochemical testing.
AB  - : DXA-measured lean mass is often used to assess muscle mass but has limitations.
      Thus, we compared DXA lean mass with two novel methods-bioelectric impedance
      spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did
      not measure lean mass similarly and the correlation with muscle
      biomarkers/function varied. INTRODUCTION: Muscle function tests predict adverse
      health outcomes better than lean mass measurement. This may reflect limitations
      of current mass measurement methods. Newer approaches, e.g., bioelectric
      impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more
      accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle
      mass would better correlate with function and bone/muscle biomarkers than DXA
      measured lean mass. METHODS: Evaluations of muscle/lean mass, function, and serum
      biomarkers were obtained in older community-dwelling adults. Mass was assessed by
      DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump
      power were examined. Potential muscle/bone serum biomarkers were measured. Mass
      measurements were compared with functional and serum data using regression
      analyses; differences between techniques were determined by paired t tests.
      RESULTS: Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years.
      The lean/muscle mass assessments were correlated (.57-.88) but differed (p <
      0.0001) from one another with DXA total body less head being highest at 37.8
      (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular
      water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength
      and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat
      chair rise. Lean mass measures were unrelated to the serum biomarkers measured.
      CONCLUSIONS: These three methodologies do not similarly measure muscle/lean mass
      and should not be viewed as being equivalent. Functional tests assessing maximal
      muscle strength/power (grip strength and jump power) correlated with all mass
      measures whereas gait speed was not. None of the selected serum measures
      correlated with mass. Efforts to optimize muscle mass assessment and identify
      their relationships with health outcomes are needed.

PMID- 29198076
TI  - Early diagnosis of osteoporosis using radiogrammetry and texture analysis from
      hand and wrist radiographs in Indian population.
AB  - : We propose an automated low cost tool for early diagnosis of onset of
      osteoporosis using cortical radiogrammetry and cancellous texture analysis from
      hand and wrist radiographs. The trained classifier model gives a good performance
      accuracy in classifying between healthy and low bone mass subjects. INTRODUCTION:
      We propose a low cost automated diagnostic tool for early diagnosis of reduction
      in bone mass using cortical radiogrammetry and cancellous texture analysis of
      hand and wrist radiographs. Reduction in bone mass could lead to osteoporosis, a
      disease observed to be increasingly occurring at a younger age in recent times.
      Dual X-ray absorptiometry (DXA), currently used in clinical practice, is
      expensive and available only in urban areas in India. Therefore, there is a need
      to develop a low cost diagnostic tool in order to facilitate large-scale
      screening of people for early diagnosis of osteoporosis at primary health
      centers. METHODS: Cortical radiogrammetry from third metacarpal bone shaft and
      cancellous texture analysis from distal radius are used to detect low bone mass.
      Cortical bone indices and cancellous features using Gray Level Run Length
      Matrices and Laws' masks are extracted. A neural network classifier is trained
      using these features to classify healthy subjects and subjects having low bone
      mass. RESULTS: In our pilot study, the proposed segmentation method shows 89.9
      and 93.5% accuracy in detecting third metacarpal bone shaft and distal radius
      ROI, respectively. The trained classifier shows training accuracy of 94.3% and
      test accuracy of 88.5%. CONCLUSION: An automated diagnostic technique for early
      diagnosis of onset of osteoporosis is developed using cortical radiogrammetric
      measurements and cancellous texture analysis of hand and wrist radiographs. The
      work shows that a combination of cortical and cancellous features improves the
      diagnostic ability and is a promising low cost tool for early diagnosis of
      increased risk of osteoporosis.

PMID- 29198077
TI  - Fibroblast-like synoviocyte migration is enhanced by IL-17-mediated
      overexpression of L-type amino acid transporter 1 (LAT1) via the mTOR/4E-BP1
      pathway.
AB  - In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to
      invade joint cartilage, actively contributing to joint destruction in RA. The
      mechanisms underlying this cell migration and invasion remain unclear. Our
      previous results and data from the GEO profile indicate that the L-type amino
      acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify
      its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with
      RA were used to determine the effects of suppressing the LAT1 genes using RNA
      interference and the LAT inhibitor, BCH. We found that BCH exposure reduced the
      phosphorylation of mTOR and its downstream target 4EBP1, radiolabeled leucine
      uptake, and migration of RA FLS. LAT1 silencing by siRNA presented effects
      similar to BCH inhibition. Treatment of cells with IL-17 stimulated the
      expression of LAT1. In contrast, applying an inhibitor of mTOR pathway,
      temsirolimus, or silencing eIF4E neutralized the stimulation of IL-17 on LAT1.
      BCH and siLAT1 also resulted in lower IL-17-stimulated leucine uptake and cell
      migration. These results suggest that the migration of RA FLS is aggravated by IL
      17-mediated overexpression of LAT1 via mTOR/4E-BP1 pathway. In conclusion,
      further investigation is warranted into LAT1 as a potential target for drug
      therapies aimed at attenuating migration of transformed-appearing fibroblasts and
      subsequently preventing further erosion of bone and cartilage.

PMID- 29198078
TI  - Targeting VEGF receptors with non-neutralizing cyclopeptides for imaging
      applications.
AB  - Pharmacological strategies aimed at preventing cancer growth are in most cases
      paralleled by diagnostic investigations for monitoring and prognosticating
      therapeutic efficacy. A relevant approach in cancer is the suppression of
      pathological angiogenesis, which is principally driven by vascular endothelial
      growth factor (VEGF) or closely related factors and by activation of specific
      receptors, prevailingly VEGFR1 and VEGFR2, set on the surface of endothelial
      cells. Monitoring the presence of these receptors in vivo is henceforth a way to
      predict therapy outcome. We have designed small peptides able to bind and
      possibly antagonize VEGF ligands by targeting VEGF receptors. Peptide systems
      have been designed to be small, cyclic and to host triplets of residues known to
      be essential for VEGF receptors recognition and we named them 'mini-factors'.
      They have been structurally characterized by CD, NMR and molecular dynamics (MD)
      simulations. Mini-factors do bind with different specificity and affinity VEGF
      receptors but none blocks receptor activity. Following derivatization with
      suitable tracers they have been employed as molecular probes for sensing
      receptors on cell surface without affecting their activity as is usually observed
      with other binders having neutralizing activity.

PMID- 29198079
TI  - Thromboxane inhibition during concurrent therapy with low-dose aspirin and over
      the-counter naproxen sodium.
AB  - : Aspirin is the dominant antiplatelet therapy for cardiovascular disease.
      Naproxen is frequently used in aspirin-treated patients and may influence the
      antiplatelet effect of aspirin. We evaluated the pharmacodynamic interaction
      (lower bound of the one-sided 95% CI for serum TxB2 inhibition < 95%) between 220
      mg immediate-release naproxen sodium (once or twice daily) and 81 mg daily
      immediate release aspirin at various dosing intervals. There was no interaction
      during the first day of concurrent treatment. After 10 days, irrespective of the
      timing and dose of naproxen in relation to aspirin dosing, a pharmacodynamic
      interaction occurred which persisted after discontinuing naproxen. In the control
      group (aspirin alone), the lower bound for serum TxB2 inhibition was > 98% at all
      time points. The clinical relevance of these observations remains unknown and
      merits further investigation since over-the-counter naproxen is widely used to
      relieve pain by individuals taking low dose aspirin for cardioprotection.
      CLINICAL TRIAL REGISTRATION: NCT02229461.

PMID- 29198080
TI  - Laboratory measurement of apixaban using anti-factor Xa assays in acute ischemic
      stroke patients with non-valvular atrial fibrillation.
AB  - Apixaban is effective and safe for preventing stroke, and its usage has increased
      exponentially in recent years. However, data concerning the therapeutic range of
      apixaban is limited. This study determined the trough and peak levels of apixaban
      specific anti-factor Xa activity (AFXaA) in acute ischemic stroke patients with
      non-valvular atrial fibrillation (NVAF) in Korea. The study included 85 patients
      who received apixaban. Blood samples were taken to measure the trough and peak
      levels of AFXaA using a chromogenic anti-factor assay, as well as prothrombin
      time (PT) and activated partial thromboplastin time (aPTT). We also reviewed
      complications such as major bleeding of patients treated with apixaban. In
      patients given a 5.0-mg apixaban dose, the median trough and peak levels of AFXaA
      were 104.5 and 202.0 ng/mL. In patients given a 2.5-mg apixaban dose, the median
      trough and peak AFXaA levels were 76.0 and 151.0 ng/mL. The PT showed a positive
      correlation with increased AFXaA activity at both levels (Trough R = 0.486, Peak
      R = 0.592), but the aPTT had no relationship with AFXaA activity at both levels
      (Trough R = 0.181, Peak R = 0.129). Two cases with intracranial bleeding belonged
      to the highest AFXaA quartile (Trough, p = 0.176; Peak, p = 0.053). In
      conclusion, we determined the trough and peak levels of AFXaA in patients with
      NVAF while being treated with the apixaban in Korea. Our results could be used as
      a starting point when setting the reference ranges for laboratories using anti-Xa
      assay. Large-scale studies are needed to establish the reference range for AFXaA
      in patients with NVAF.

PMID- 29198081
TI  - Anaerobic crystallization of proteins.
AB  - Crystallization has been a bottleneck in the X-ray crystallography of proteins.
      Although many techniques have been developed to overcome this obstacle, the
      impurities caused by chemical reactions during crystallization have not been
      sufficiently considered. Oxidation of proteins, which can lead to poor
      reproducibility of the crystallization, is a prominent example. Protein
      oxidization in the crystallization droplet causes inter-molecular disulfide
      bridge formation, formation of oxidation film, and precipitation of proteins.
      These changes by oxidation are typically irreversible. The best approach for
      preventing protein oxidization during crystallization is anaerobic
      crystallization. Here we review the anaerobic crystallization of proteins, which
      was originally developed to trap a reaction intermediate of the enzyme in the
      crystal. We also summarize representative anaerobic crystallizations from our
      laboratory and the general setup of anaerobic crystallization.

PMID- 29198082
TI  - Protein-solvent interaction.
AB  - Protein folding and assembly can be manipulated in in vitro systems by co
      solvents at high concentrations. A number of co-solvents that enhance protein
      stability and assembly have been shown to be excluded from the protein surface.
      Such co-solvent exclusion has been demonstrated by dialysis experiments and shown
      to be correlated with their effects on protein stability and assembly.

PMID- 29198083
TI  - ROBOTIC-ASSISTED TRANSAXILLARY THYROID SURGERY - THE RABIN MEDICAL CENTER
      EXPERIENCE
AB  - AIMS: To review the experience of a single-center with RATS and to assess its
      outcome, feasibility and safety. BACKGROUND: With the advent of minimally
      invasive techniquesin thyroid surgery, robot-assisted transaxillary thyroid
      surgery (RATS) has become one of the most popular approaches. Its main advantages
      are improved cosmetic outcome, thereby increasing patient satisfaction, improved
      visualization and range of motion. Several large-scale studies, have demonstrated
      its safety and feasibility. METHODS: A retrospective review of all RATS
      consecutive cases at Rabin Medical Center. RESULTS: A total of 38 RATS procedures
      were performed between July 2012 and May 2015. The mean age of patients was 39
      years (22-74); all patients were females; the average BMI was 25 (18-32). Thirty
      seven patients underwent partial thyroidectomy and one - total thyroidectomy. The
      average maximal diameter of nodules pre-operatively was 2.5 cm (0.5- 5).
      Seventeen patients (44%) had papillary carcinoma; 13 (33%) - hyperplastic nodules
      and 8 (20%) - benign thyroid adenomas or goiters. The average total operative
      time was 166 minutes. One case was converted to open due to a large tumor; there
      were 6 (15.7%) cases of vocal cord paresis, of which 1 (2.6%) was permanent;
      there were 8 (21%) cases of hypoesthesia - all resolved within 4-12 weeks. There
      were no cases of permanent brachial plexus injury. CONCLUSIONS: In skilled hands,
      RATS is a safe alternative to conservative thyroidectomy, and should be presented
      to patients with aesthetic concerns. As with any new emerging technique, careful
      patient selection is crucial and further evidence must be sought to confirm its
      indications over time.

PMID- 29198084
TI  - [THE IMPACT OF MOLECULAR PROFILING USING NEXT-GENERATION SEQUENCING IN ADVANCED
      LUNG CANCER].
AB  - BACKGROUND: In the last decade, important advances in understanding the lung
      cancer cellular signal pathways have led to the designing of targeted drugs that
      significantly prolong survival. Recent data shows that 64% of lung
      adenocarcinomas harbor at least one activating driver mutation, including
      treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides
      the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS)
      reveals more clinically meaningful genomic alterations as compared to currently
      used diagnostic tests. However, the clinical impact of NGS testing merits further
      investigation. OBJECTIVES: To evaluate the impact of NGS-based tumor profiling on
      therapeutic decision making in the real life setting in advanced lung cancer
      patients. METHODS: The study population included 50 lung cancer patients who were
      treated at Davidoff Cancer Center, Rabin Medical Center in 2011-2015, and for
      whom a broad, hybrid capture-based NGS genomic profiling test was performed. The
      data was retrospectively collected from patient charts. RESULTS: 39 of 46
      included patients (84.8%) had one or more driver alternations, and a targeted
      agent was administered according to alteration discovered in 21 of 46 cases
      (45.7%). 15 (37.5%) treated patients were exclusively detected by NGS. The most
      frequent drivers were EGFR (26.1%), KRAS (19.6%), ALK (13%), STK11 (10.9%) and
      RET (8.7%). Interestingly, 10 patients became EGFR and ALK positive by NGS after
      the previous standard local molecular testing was negative. CONCLUSIONS:
      Molecular testing using NGS can reveal a targetable genomic alteration in the
      vast majority of lung tumors. Its broad use for therapeutic decision making is
      essential since approximately half of the patients can benefit from customized
      treatment upon testing results. DISCUSSION: Although this topic needs to be
      further assessed in large randomized controlled trials, our positive results
      emphasize the importance of multiplex testing as a diagnostic test in advanced
      lung cancer patients. The implementation of NGS at Rabin Medical Center in the
      near future is highly anticipated.

PMID- 29198085
TI  - [THE DIAGNOSTIC AND THERAPEUTIC CHALLENGE OF TYPE 2 MYOCARDIAL INFRACTION].
AB  - INTRODUCTION: Type 2 Myocardial Infarction (Type 2 MI) is considered to result
      from an imbalance between demand and supply of oxygen in the myocardium, other
      than coronary plaque instability. It is highly prevalent in internal departments
      and is strongly associated with mortality. To date, there is no consensus
      regarding the diagnostic criteria for type 2 MI and no available guidelines
      regarding the optimal management of this condition. We present a case study of a
      64 years old male who was hospitalized with lower gastrointestinal bleeding. This
      patient was diagnosed with Type 2 myocardial infarct, due to a decrease in oxygen
      supply to the myocardium, but eventually turned out to be a Type 1 MI .We
      reviewed current literature regarding the clinical features, diagnosis, prognosis
      and treatment of Type 2 MI.

PMID- 29198086
TI  - [INR LEVELS DURING HOSPITALIZATION AT THE DEPARTMENT OF MEDICINE].
AB  - BACKGROUND: Warfarin has a narrow therapeutic index with INR values between 2.0 -
      3.0. According to our clinical experience, control of INR levels during
      hospitalization is poor. OBJECTIVES: The study aimed to evaluate control of INR
      levels during hospitalization in the departments of internal medicine, to
      determine the factors that influence INR levels during hospitalization, and the
      association between the control of INR levels before and during hospitalization.
      METHODS: This is a retrospective study, including the data of patients who were
      admitted to the internal medicine wards at Meir and Rabin Medical Centers,
      Israel, between May 2011 and May 2013. Inclusion criteria: patients who were
      treated with warfarin prior and during the index hospitalization and at least 3
      INR tests were taken during the hospitalization and the 3 months before it. The
      collected data included: demographic parameters (age, gender), medical
      background, cause of admission, relevant medications for INR control, duration of
      hospitalization and INR values. The INR control during hospitalization and the
      previous 3 months, the parameters that affect INR levels and the association
      between control before and during hospitalization were evaluated. RESULTS: Of
      1861 screened patients, only 299 filled the inclusion criteria. Among those
      patients, 93 (31%) were considered to have well controlled INR rates during the
      hospitalization. No significant differences were found between the controlled and
      uncontrolled groups. The risk of a well-controlled patient before admission to be
      uncontrolled during admission was 63%, whereas the risk of an uncontrolled
      patient before admission to remain uncontrolled during hospitalization was 73%.
      CONCLUSIONS: By using a larger study group it might be possible to achieve
      significant results and to set guidelines for INR control during admission.
      DISCUSSION: Most patients are not monitored well enough to estimate their degree
      of INR control. Most of the patients, who could be evaluated, were uncontrolled.

PMID- 29198087
TI  - [TRAINING WORKSHOPS FOR BEDOUIN MOTHERS: PREVENTION OF IRON DEFICIENCY ANEMIA IN
      CHILDREN - RESULTS FROM A COMMUNITY TRIAL STUDY].
AB  - INTRODUCTION: Anemia is the most common nutritional deficiency in the world,
      contributing to childhood morbidity and mortality. Knowledge, attitudes and
      behavior of caretakers and parents of toddlers can significantly prevent anemia.
      OBJECTIVES: Assessment of workshop intervention to alter knowledge, attitudes and
      behavior in mothers of toddlers in the Bedouin population. METHODS: Community
      trial study. The intervention group included: 150 mothers of healthy one-year-old
      toddlers receiving workshops culturally tailored for a month in addition to
      standard training in "Tipat-Halav" (Baby clinic). The control group included: 101
      mothers of healthy one-year-old toddlers who received standard training. At the
      endpoint, mothers were tested in both groups to determine levels of knowledge
      based on the knowledge and attitudes questionnaire, and the food intake of their
      children was reviewed according to the Food Frequency Questionnaire (FFQ).
      RESULTS: Intervention group mothers correctly answered significantly more
      questions on knowledge and attitudes than the control group; 87.3% of the
      intervention group recognized the importance of giving iron supplements to
      prevent anemia compared to 73.3% in the control group (p=0.004). Over three
      quarters of the intervention group and half of the control group knew that food
      affects mental development (p=0.001). In logistic regression, neutralization of
      SES variables, the intervention increased the rate mothers correctly answered
      questions 2 to 2.6 fold compared with the control group (p?0.05). According to
      the FFQ, children in the intervention group ate more iron-rich foods of animal
      and vegetarian origin compared to the control group (p<0.05). CONCLUSIONS: The
      intervention improved the knowledge and behavior of mothers in preventing anemia
      in toddlers. It should be required to provide information and training activities
      for mothers of toddlers beyond standard training, increasing the awareness of
      foods rich in iron. This activity can be performed using cultural workshops on
      iron deficiency, as was performed in this study.

PMID- 29198088
TI  - [EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS
      DEFICIENCY].
AB  - INTRODUCTION: Bronchiectasis is characterized by an abnormal dilatation of the
      bronchi leading to a chronic inflammatory process, airway blockage and impaired
      clearance of secretions. The damage to the airways is usually progressive and is
      the result of several pathogenic processes. In the past, healing of infections
      (especially pulmonary tuberculosis) was the main cause of airway dilatation and
      progression of chronic inflammation. Today, congenital illnesses, anatomical
      defects and immune deficiency play an important role in the pathogenesis of
      bronchiectasis formation. The immunoglobulin repertoire is vital for effective
      host protection against a wide variety of pathogens. Primary antibody deficiency
      diseases are defects of the humoral arm of the immune system and involve an
      absence/reduced levels of one or more immunoglobulin classes/subclasses or
      defects of specific antibody formation. Immunoglobulin G (IGG) subclass
      deficiency can occur in a healthy person and could be without clinical
      significance. However, in recent years there is emerging evidence that in
      patients with recurrent infections, early diagnosis of antibody deficiency
      affects the prognosis and prevention of ongoing lung damage. The use of IVIG has
      contributed significantly to the survival rate in primary antibody deficiencies.
      There is limited literature on the treatment of IVIG for patients with IGG
      subclass deficiency. However, all studies presented so far demonstrated that
      immunoglobulin therapy reduced the rate of bacterial infections, days of
      antibiotic usage, hospital admissions and significantly increased patients'
      quality of life. Therefore, in the appropriate clinical setting, ie: a patient
      with bronchiectasis and recurrent infections, it is justified to test whether
      there are humoral immune defects such as IGG subclass deficiency. In a patient
      with proven deficiency, we should recommend to start IVIG treatment until
      clinical benefit is achieved.

PMID- 29198089
TI  - [EXOSOMES AS MEDIATORS OF INTERCELLULAR COMMUNICATION: THE CANCER AND TELOMERASE
      CONNECTION].
AB  - INTRODUCTION: Exosomes, nano-vesicles secreted from all types of cells in the
      human body, function as inter-cell communicators. This role of exosomes is
      fulfilled by their specific content, dependent on the origin of donor cells from
      which they are secreted. Exosomes contain a plethora of nucleic acids (DNA, RNA
      and micro RNA), proteins and lipids. These molecules are packed in the donor
      cells into the exosomes which are subsequently secreted and transferred through
      various body fluids into the target cells which may be located far from the donor
      cells. Recently, the issue of exosome research has been widely expanded and data
      has been accumulated regarding the relevance and involvement of exosomes in
      cancer. Exosomes play a role in the process of malignant transformation, in
      avoiding the surveillance of the immune system, the expansion of the tumor and
      its establishment in the cancer microenvironment. In addition, exosomes promote
      the process of metastasis formation. Among other subjects, exosomal research
      focuses around the characterization of the content of cancer-derived exosomes in
      order to identify markers that can be used for diagnosis and prognosis of cancer
      patients. Telomerase, a unique reverse transcriptase, has been widely shown to be
      crucial for the process of malignant transformation and the perpetuation of the
      malignant clone. In the current review, we describe the importance of exosomes to
      the various themes of cancer and their potential use as diagnostic and prognostic
      markers as well as their therapeutic potential. In addition, the results and
      implications of our study with regards to the secretion of telomerase transcript
      into exosomes derived from cancer cells will be discussed.

PMID- 29198090
TI  - [CO-OCCURRING SCHIZOPHRENIA AND SUBSTANCE USE DISORDER: ETIOLOGICAL THEORIES AND
      CHALLENGES IN ISRAEL].
AB  - INTRODUCTION: A sizeable number of patients suffering from psychotic disorders,
      particularly schizophrenia, are also diagnosed with substance use disorder (SUD).
      These dual diagnosis (DD) patients are considered very difficult to treat and
      differ in some of their characteristics from patients with schizophrenia or SUD
      exclusively. They have a worse prognosis and require more complex treatment which
      needs to be integrated for both of the disorders. In Israel there is a lack of
      training, professionals and institutions specializing in treatment for this
      population. Consequently, many DD patients are left without care in the community
      and as a result, their relapses and hospitalizations are more frequent. In
      addition, many of the patients are not accepted to the existing institutions due
      to the requirement that the patient has to express clear motivation to stop his
      substance abuse. In this article we will review etiological theories of the
      comorbidity between chronic psychotic disorders and SUD. These theories explain
      the unique difficulty of DD patients to develop motivation to quit or diminish
      substance abuse. The data presented here sheds light on the gap between the needs
      of these patients and the current situation in Israel, urging the need to change
      the approach and adapt treatments for this unique population.

PMID- 29198091
TI  - [TREATMENTS FOR SLOWING THE PROGRESSION OF MYOPIA].
AB  - INTRODUCTION: Myopia is the most common refractive error and is now endemic over
      the entire industrial world, particularly in Asia. High myopia is one of the
      major causes of blindness in the world. Slowing the progress of myopia is
      possible, the most effective treatment being atropine ophthalmic drops, given in
      a dose-dependent fashion. Although high-dose atropine (1% and 0.5%) was found to
      be highly effective in slowing myopia progression, low-dose atropine (0.01%) was
      found to have the lowest rebound effect (accelerated myopia progression after
      treatment cessation) and was therefore, the most effective treatment in the long
      term. Moderately effective treatments include pirenzepine drops, cyclopentolate
      drops, orthokeratology, contact lenses which are designed to reduce the
      peripheral hyperopic blur and distance-center soft multifocal contact lenses.
      Less effective treatments include multifocal spectacle lenses, bifocal spectacle
      lenses, bifocal soft contact lenses and outdoor activity in daylight. Visual
      therapy, biofeedback, full-spectacle correction, under-correction, spectacles
      designed to reduce the peripheral hyperopic blur, single-vision rigid gas
      permeable contact lenses, single-vision soft contact lenses, tropicamide drops
      and timolol drops were all found to be ineffective.

PMID- 29198092
TI  - [THE ISRAELI NEUROGASTROENTEROLOGY ASSOCIATION RECOMMENDATIONS FOR THE EVALUATION
      AND TREATMENT OF CHRONIC CONSTIPATION].
AB  - INTRODUCTION: This article summarizes the recommendations of the Israeli
      Neurogastroenterology and Motility Branch of the Israeli Gastroenterology
      Association for diagnosis and treatment of chronic constipation. It encompasses
      an overview of the definitions, the diagnostic approach and the possible
      treatment options in chronic constipation. This document is suitable for primary
      care physicians who are interested in understanding the major physiologic
      mechanisms for chronic constipation and the possible treatment options, as well
      as for the gastroenterology consultant who faces patients with tenacious chronic
      constipation.

PMID- 29198093
TI  - [STRENUOUS AND PROLONGED EXERCISE AND UPPER RESPIRATORY TRACT INFECTION -
      TREATMENT OR THREAT?]
AB  - INTRODUCTION: Prolonged and strenuous exercise may lead to changes in the immune
      system function and to temporary suppression in defense against pathogens. These
      changes likely increase the risk of those engaging in prolonged and strenuous
      physical activity to develop upper respiratory tract infection and to reduce the
      level of performance. On the other hand, it appears that moderate physical
      activity reduces the risk of upper respiratory tract infection. Various
      populations, such as professional athletes and soldiers in combat units, who
      engage in daily strenuous exercise, may therefore be a high risk group.
      Integration of additional stress factors, such as sleep deprivation, emotional
      stress, nutritional deprivation, and dehydration also affect the immune system
      and may worsen the effect. On the other hand, there are those who claim that
      upper respiratory symptoms are due to non-infection inflammation causes such as
      allergy, asthma etc. Hence the effects of strenuous exercise on the immune system
      during training and competitions are not sufficiently clear. This review article
      will focus on the known effects of strenuous and prolonged exercise on the immune
      system, the possible mechanisms leading to these changes and their clinical
      impacts with applied emphasis to active populations such as athletes and
      soldiers.

PMID- 29198094
TI  - [FROM PASTORAL CARE TO SPIRITUAL CARE - TRANSFORMING THE CONCEPTION OF THE ROLE
      OF THE SPIRITUAL CARE PROVIDER].
AB  - INTRODUCTION: Spirituality is a difficult concept to define, one that is often
      understood differently by different cultures and religious communities. Illness
      constitutes a dramatic change in the ongoing flow and norms of a person's life,
      raising questions of the value or meaning of life, questions of self-worth, and
      questions of forgiveness, to ourselves and others. The profession of spiritual
      care comes to provide support in these areas. Originally focused on religious
      care, the profession has shifted to providing care for general spiritual well
      being, where professionals care for all patients regardless of religion. This
      survey presents the impact of spiritual well-being on patients in times of
      serious illness, as distinct from religious well-being, and the role of the
      spiritual care provider in supporting patients who are in spiritual distress.
      Studies demonstrate the connection between spiritual or religious well-being and
      various clinical measures for advanced illness. Studies of spiritual well-being,
      as distinct from religious well-being, found a direct connection between higher
      spiritual well-being and reduced depression and despair among cancer and AIDS
      patients and improved survival rates among patients with congestive heart
      failure. Religious struggle has been found to correlate with lowered survival
      rates for hospitalized elderly patients, and with more prolonged hospital stays
      among patients with congestive heart failure. Negative religious coping has been
      found to correlate with depression, anxiety, and decreased quality of life among
      patients undergoing bone-marrow transplants, cancer patients, and patients with
      end-stage renal disease. In order to integrate the spiritual care provider into
      the multidisciplinary hospital team, a model has been proposed for staff to
      perform a short spiritual history at intake relating to patients' beliefs and the
      importance they hold for the patient. The staff person learns to be attentive to
      key points indicating a referral to spiritual care. Spiritual needs addressed by
      the spiritual care provider may include aligning care plans with patients'
      values, promoting a sense of peace, lessening isolation, and enabling mourning.
      In Israel, spiritual care is a new profession, not carrying with it the baggage
      of earlier models which limited this profession to religious leaders, a fact
      which enables better integration of the spiritual care provider into the
      multidisciplinary staff.

PMID- 29198095
TI  - Is it possible to predict the development of an entecavir resistance mutation in
      patients with chronic hepatitis B in clinical practice?

PMID- 29198096
TI  - Prognostic Factors and Decision Tree for Long-Term Survival in Metastatic Uveal
      Melanoma.
AB  - PURPOSE: The purpose of this study was to demonstrate the existence of a bimodal
      survival pattern in metastatic uveal melanoma. Secondary aims were to identify
      the characteristics and prognostic factors associated with long-term survival and
      to develop a clinical decision tree. Materials and Methods: The medical records
      of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients
      were classified as either short (<= 12 months) or long-term survivors (> 12
      months) based on a graphical interpretation of the survival curve after diagnosis
      of the first metastatic lesion. Ophthalmic and oncological characteristicswere
      assessed in both groups. RESULTS: Of the 99 patients, 62 (62.6%) were classified
      as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate
      analysis identified the following predictors of long-term survival: age <= 65
      years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018);
      additionally, the size (smaller vs. larger) of the largest liver metastasis
      showed a trend towards significance (p=0.063). Based on the variables
      significantly associated with long-term survival, we developed a decision tree to
      facilitate clinical decision-making. CONCLUSION: The findings of this study
      demonstrate the existence of a bimodal survival pattern in patients with
      metastatic uveal melanoma. The presence of certain clinical characteristics at
      diagnosis of distant disease is associated with long-term survival. A decision
      tree was developed to facilitate clinical decision-making and to counsel patients
      about the expected course of disease.

PMID- 29198097
TI  - HBsAg-Negative, Anti-HBc-Negative Patients Still Have a Risk of Hepatitis B Virus
      Related Hepatitis after Autologous Stem Cell Transplantation for Multiple Myeloma
      or Malignant Lymphoma.
AB  - PURPOSE: Although hepatitis B surface antigen (HBsAg)-negative, hepatitis B core
      antibody (anti-HBc)-negative patients are not considered to be at risk for
      hepatitis B virus (HBV)-related hepatitis, the actual risk remains to be
      elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in
      HBsAg-negative, anti-HBc-negative patients receiving autologous stem cell
      transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. Materials
      and Methods: We retrospectively reviewed data from 271 HBsAg-negative patients
      (161 anti-HBc-negative and 110 anti-HBc-positive at the time of ASCT) who
      received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed
      according to the presence of anti-HBc. HBV serology results at the time of ASCT
      were compared with those at the time of diagnosis of MM or lymphoma. RESULTS:
      Three patients (two anti-HBc-negative MMs and one anti-HBc-positive MM) developed
      HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not
      differ among patients with or without anti-HBc status (p=0.843). HBV-related
      hepatitis more frequently occurred in MM patients than in lymphoma patients
      (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who
      were HBsAg-negative and anti-HBc-positive at the time of diagnosis had lost anti
      HBc positivity during chemotherapy prior to ASCT. CONCLUSION: Our data suggest
      that HBsAg-negative, anti-HBc-negative patients at the time of ASCT for MM or
      lymphoma still might be at a risk for HBV-related hepatitis.

PMID- 29198098
TI  - Role of local government in responding to environmental health challenges: a case
      study of Chungnam.
AB  - The purpose of this study is to introduce the establishment process, policy
      target, and projects for "Chungnam's master plan on environmental health policy
      (2017-2020)" as the local government's role in addressing local environmental
      health challenges. We first analyzed existing studies and social issues on the
      media related to "Chungnam's master plan" to understand Chungnam's environmental
      health status and discussed domestic and international policy trends and related
      plans. An environmental health perception questionnaire survey and a Delphi
      expert questionnaire survey were conducted among provincial residents to collect
      various actors' opinions on Chungnam's environmental health issues and policy. An
      expert advisory panel was launched, and a residents' voice workshop and cities
      and-guns-policy-suggestion workshop were held. The vision of Chungnam's
      environmental health policy is minimizing environmental hazards. We finally
      selected "Pleasant environment, healthy people, happy Chungnam" to represent the
      will to shape a pleasant environment and prevent and manage health damages for a
      happy Chungnam. We selected five strategies based on status analysis and a review
      of domestic and international policy trends and related plans and identified 2
      targets (policy objectives) to accomplish the strategies. The strategies to
      achieve the first target, "Leader in environmental health policy: Chungnam,"
      include 'Empowering active provincial capabilities,' 'Setting up province
      specific systems for environmental health surveys and research,' and 'Preventing
      and managing newly emerging pollutants.' The strategies for the second target,
      "Everyone is healthy: Chungnam," include 'Relieving health inequalities among
      vulnerable regions and residents' and 'Enlarging the resident-friendly
      environmental health policy.' We developed 29 projects in total, according to
      these strategies. The establishment of "Chungnam's master plan" is highly
      valuable; we developed it through discussion involving diverse actors to address
      environmental health challenges together. It is necessary to continue to
      strengthen participation, communication, and cooperation among actors to develop
      an environmental health policy model for the future.

PMID- 29198099
TI  - Determination of Fosetyl and Phosphonic Acid at 0.010 mg/kg Level by Ion
      Chromatography Tandem Mass Spectrometry.
AB  - A new sensitive, fast, and robust method using ion chromatography tandem mass
      spectrometry (IC-MS/MS) for the determination of fosetyl and phosphonic acid in
      plant-derived matrices was developed. For compensation of matrix effects and
      differences in recovery rates the isotopically labeled internal standard (ILIS)
      18O3-labeled phosphonic acid was added to the samples prior to the extraction of
      the target compounds. The validation of the method for the matrices tomato,
      apple, lemon, sultana, avocado, and wheat was performed according to the actual
      EU guidance document SANTE/11945/2015. The precision and accuracy were determined
      in five replicates at spiking levels of 0.010 and 0.100 mg/kg with recovery rates
      between 76 and 105% and RSDs between 1.2 and 17.8%. In this paper, it was
      achieved for the first time to detect both fosetyl and phosphonic acid at the
      reporting level of 0.010 mg/kg most relevant for organic plant food commodities.

PMID- 29198100
TI  - Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich
      Reactions between alpha,beta- and beta,gamma-Butenolides and Aldimines.
AB  - We report a Zn-ProPhenol catalyzed reaction between butenolides and imines to
      obtain tetrasubstituted vinylogous Mannich products in good yield and
      diastereoselectivity with excellent enantioselectivity (97 to >99.5% ee).
      Notably, both alpha,beta- and beta,gamma-butenolides can be utilized as
      nucleophiles in this transformation. The imine partner bears the synthetically
      versatile N-Cbz group, avoiding the use of the specialized aryl directing groups
      previously required in related work. Additionally, the reaction can be performed
      on gram scale with reduced catalyst loading as low as 2 mol %. The functional
      group-rich products can be further elaborated using a variety of methods.

PMID- 29198101
TI  - Multiplexed Detection of Foodborne Pathogens from Contaminated Lettuces Using a
      Handheld Multistep Lateral Flow Assay Device.
AB  - This paper presents a handheld device that is capable of simplifying multistep
      assays to perform sensitive detection of foodborne pathogens. The device is
      capable of multiplexed detection of Escherichia coli (E. coli) O157:H7,
      Salmonella Typhimurium (S. Typhimurium), Staphylococcus aureus, and Bacillus
      cereus. The limit of detection for each bacterium was characterized, and then,
      the detection of bacteria from contaminated fresh lettuces was demonstrated for
      two representative foodborne pathogens. We employed a sample pretreatment
      protocol to recover and concentrate target bacteria from contaminated lettuces,
      which can detect 1.87 * 104 CFU of E. coli O157:H7 and 1.47 * 104 CFU of S.
      Typhimurium/1 g of lettuce without an enrichment process. Lastly, we demonstrated
      that the limit of detection can be reduced to 1 CFU of E. coli O157:H7 and 1 CFU
      of S. Typhimurium/1 g of lettuce by including a 6 h enrichment of contaminated
      lettuces in growth media before pretreatment.

PMID- 29198103
TI  - Time Trends in Per- and Polyfluoroalkyl Substances (PFASs) in California Women:
      Declining Serum Levels, 2011-2015.
AB  - After several decades of widespread use, some per- and polyfluoroalkyl substances
      (PFASs) were phased-out of use due to concerns raised by their persistent,
      bioaccumulative, and toxic properties. Our objective was to evaluate temporal
      trends in serum PFAS levels among 1257 middle-aged and older California women
      (ages 40-94) during a four year period, beginning approximately 5-10 years after
      these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long
      chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from
      a subset of participants in the California Teachers Study. Results from
      multivariable linear regression analyses indicated that serum concentrations of
      nearly all PFASs declined on average 10% to 20% per year. Serum levels of
      perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the
      exception of PFHxS, the downward trend in serum concentrations was evident for
      all PFASs across all ages, although declines were comparatively steeper among the
      oldest women. These findings suggest that the phase-out of some common PFASs has
      resulted in reduced human exposures to them. The lack of a decline for PFHxS
      suggests that these exposures may be ongoing and underscores the importance of
      continued biomonitoring and research efforts to elucidate current pathways of
      exposure.

PMID- 29198102
TI  - Antimicrobial and Antibiofilm Activity of Human Milk Oligosaccharides against
      Streptococcus agalactiae, Staphylococcus aureus, and Acinetobacter baumannii.
AB  - In a previous study, we reported that human milk oligosaccharides (HMOs) isolated
      from five donor milk samples possessed antimicrobial and antibiofilm activity
      against Streptococcus agalactiae, also known as Group B Streptococcus or GBS.
      Herein, we present a broader evaluation of the antimicrobial and antibiofilm
      activity by screening HMOs from 14 new donors against three strains of GBS and
      two of the ESKAPE pathogens of particular interest to child health,
      Staphylococcus aureus and Acinetobacter baumannii. Growth and biofilm assays
      showed that HMOs from these new donors possessed antimicrobial and antibiofilm
      activity against all three strains of GBS, antibiofilm activity against
      methicillin-resistant S. aureus strain USA300, and antimicrobial activity against
      A. baumannii strain ATCC 19606.

PMID- 29198104
TI  - Highly Selective Fluorescent Probe Based on Hydroxylation of Phenylboronic Acid
      Pinacol Ester for Detection of Tyrosinase in Cells.
AB  - The detection of tyrosinase, a biomarker for melanoma, is of great significance.
      Herein, a fluorescent tyrosinase probe, with resorufin as the fluorophore and m
      tolylboronic acid pinacol ester as the receptor, is proposed. The response relies
      on the tyrosinase-catalyzed hydroxylation of phenylboronic acid pinacol ester at
      an adjacent position followed by 1,6-rearrangement elimination to release
      resorufin. This probe well quantifies tyrosinase in the range from 1 to 100 U mL
      1 with a detection limit of 0.5 U mL-1. Importantly, the probe exhibits high
      selectivity for tyrosinase over other biological substances including reactive
      oxygen species. In addition, it is successfully applied to the imaging of
      tyrosinase in cells. This probe provides a novel platform for selective detection
      of tyrosinase in biosystems.

PMID- 29198105
TI  - Sources of Methylmercury to Snowpacks of the Alberta Oil Sands Region: A Study of
      In Situ Methylation and Particulates.
AB  - Snowpacks in the Alberta Oil Sands Region (AOSR) of Canada contain elevated
      loadings of methylmercury (MeHg; a neurotoxin that biomagnifies through foodwebs)
      due to oil sands related activities. At sites ranging from 0 to 134 km from the
      major AOSR upgrading facilities, we examined sources of MeHg by quantifying
      potential rates of MeHg production in snowpacks and melted snow using mercury
      stable isotope tracer experiments, as well as quantifying concentrations of MeHg
      on particles in snowpacks (pMeHg). At four sites, methylation rate constants were
      low in snowpacks (km = 0.001-0.004 d-1) and nondetectable in melted snow, except
      at one site (km = 0.0007 d-1). The ratio of methylation to demethylation varied
      between 0.3 and 1.5, suggesting that the two processes are in balance and that in
      situ production is unlikely an important net source of MeHg to AOSR snowpacks.
      pMeHg concentrations increased linearly with distance from the upgraders (R2 =
      0.71, p < 0.0001); however, snowpack total particle and pMeHg loadings decreased
      exponentially over this same distance (R2 = 0.49, p = 0.0002; R2 = 0.56, p <
      0.0001). Thus, at near-field sites, total MeHg loadings in snowpacks were high
      due to high particle loadings, even though particles originating from industrial
      activities were not MeHg rich compared to those at remote sites. More research is
      required to identify the industrial sources of snowpack particles in the AOSR.

PMID- 29198106
TI  - Metal-Organic Frameworks Invert Molecular Reactivity: Lewis Acidic Phosphonium
      Zwitterions Catalyze the Aldol-Tishchenko Reaction.
AB  - The influence of metal-organic frameworks (MOFs) as additives is herein described
      for the reaction of n-alkyl aldehydes in the presence of methylvinylketone and
      triphenylphosphine. In the absence of a MOF, the expected Morita-Baylis-Hillman
      product, a beta-hydroxy enone, is observed. In the presence of MOFs with UMCM-1
      and MOF-5 topologies, the reaction is selective to Aldol-Tishchenko products, the
      1 and 3 n-alkylesters of 2-alkyl-1,3-diols, which is unprecedented in
      organocatalysis. The (3-oxo-2-butenyl)triphenylphosphonium zwitterion, a commonly
      known nucleophile, is identified as the catalytic active species. This zwitterion
      favors nucleophilic character in solution, whereas once confined within the
      framework, it becomes an electrophile yielding Aldol-Tishchenko selectivity.
      Computational investigations reveal a structural change in the phosphonium moiety
      induced by the steric confinement of the framework that makes it accessible and
      an electrophile.

PMID- 29198107
TI  - Fingerprint Analysis: Moving Toward Multiattribute Determination via Individual
      Markers.
AB  - Forensic science will be forever revolutionized if law enforcement can identify
      personal attributes of a person of interest solely from a fingerprint. For the
      past 2 years, the goal of our group has been to establish a way to identify
      originator attributes, specifically biological sex, from a single analyte. To
      date, an enzymatic assay and two chemical assays have been developed for the
      analysis of multiple analytes. In this manuscript, two additional assays have
      been developed. This time, however, the assays utilize only one amino acid each.
      The enzymatic assay targets alanine and employs alanine transaminase (ALT),
      pyruvate oxidase (POx), and horseradish peroxidase (HRP). The other, a chemical
      assay, is known as the Sakaguchi test and targets arginine. It is important to
      note that alanine has a significantly higher concentration than arginine in the
      fingerprint content of both males and females. Both assays proved to be capable
      of accurately differentiating between male and female fingerprints, regardless of
      their respective average concentration. The ability to target a single analyte
      will transform forensic science as each originator attribute can be correlated to
      a different analyte. This would then lead to the possibility of identifying
      multiple attributes from a single fingerprint sample. Ultimately, this would
      allow for a profile of a person of interest to be established without the need
      for time-consuming lab processes.

PMID- 29198108
TI  - Functional and Proteomic Alterations of F1 Capacitated Spermatozoa of Adult Mice
      Following Gestational Exposure to Bisphenol A.
AB  - Studies regarding bisphenol A (BPA) exposure and male (in)fertility have
      conventionally focused on modifications in ejaculated spermatozoa function from
      exposed individuals. However, mammalian spermatozoa are incapable of
      fertilization prior to achieving capacitation, the penultimate step in
      maturation. Therefore, it is necessary to investigate BPA-induced changes in
      capacitated spermatozoa and assess the consequences on subsequent fertilization.
      Here, we demonstrate the effect of gestational BPA exposure (50 MUg/kg bw/day, 5
      mg/kg bw/day, and 50 mg/kg bw/day) on the functions, biochemical properties, and
      proteomic profiles of F1 capacitated spermatozoa from adult mice. The data showed
      that high concentrations of BPA inhibited motility, motion kinematics, and
      capacitation of spermatozoa, perhaps because of increased lipid peroxidation and
      protein tyrosine nitration, and decreased intracellular ATP levels and protein
      kinase-A activity in spermatozoa. We also found that BPA compromised the rates of
      fertilization and early embryonic development. Differentially expressed proteins
      identified between BPA-exposed and control groups play a critical role in energy
      metabolism, stress responses, and fertility. Protein function abnormalities were
      responsible for the development of several diseases according to bioinformatics
      analysis. On the basis of these results, gestational exposure to BPA may alter
      capacitated spermatozoa function and the proteomic profile, ultimately affecting
      their fertility potential.

PMID- 29198109
TI  - Surface Defect Passivation and Reaction of c-Si in H2S.
AB  - A unique passivation process of Si surface dangling bonds through reaction with
      hydrogen sulfide (H2S) is demonstrated in this paper. A high-level passivation
      quality with an effective minority carrier lifetime (taueff) of >2000 MUs
      corresponding to a surface recombination velocity of <3 cm/s is achieved at a
      temperature range of 550-650  degrees C. X-ray photoelectron spectroscopy (XPS)
      confirmed the bonding states of Si and S and provides insights into the reaction
      pathway of Si with H2S and other impurity elements both during and after the
      reaction. Quantitative analysis of XPS spectra showed that the taueff increases
      with an increase in the surface S content up to ~3.5% and stabilizes thereafter,
      indicative of surface passivation by monolayer coverage of S on the Si surface.
      However, S passivation of the Si surface is highly unstable because of
      thermodynamically favorable reaction with atmospheric H2O and O2. This
      instability can be eliminated by capping the S-passivated Si surface with a
      protective thin film such as low-temperature-deposited amorphous silicon nitride.

PMID- 29198110
TI  - Label-Free Platform for MicroRNA Detection Based on the Fluorescence Quenching of
      Positively Charged Gold Nanoparticles to Silver Nanoclusters.
AB  - A novel strategy was developed for microRNA-155 (miRNA-155) detection based on
      the fluorescence quenching of positively charged gold nanoparticles [(+)AuNPs] to
      Ag nanoclusters (AgNCs). In the designed system, DNA-stabilized Ag nanoclusters
      (DNA/AgNCs) were introduced as fluorescent probes, and DNA-RNA heteroduplexes
      were formed upon the addition of target miRNA-155. Meanwhile, the (+)AuNPs could
      be electrostatically adsorbed on the negatively charged single-stranded DNA
      (ssDNA) or DNA-RNA heteroduplexes to quench the fluorescence signal. In the
      presence of duplex-specific nuclease (DSN), DNA-RNA heteroduplexes became a
      substrate for the enzymatic hydrolysis of the DNA strand to yield a fluorescence
      signal due to the diffusion of AgNCs away from (+)AuNPs. Under the optimal
      conditions, (+)AuNPs displayed very high quenching efficiency to AgNCs, which
      paved the way for ultrasensitive detection with a low detection limit of 33.4 fM.
      In particular, the present strategy demonstrated excellent specificity and
      selectivity toward the detection of target miRNA against control miRNAs,
      including mutated miRNA-155, miRNA-21, miRNA-141, let-7a, and miRNA-182.
      Moreover, the practical application value of the system was confirmed by the
      evaluation of the expression levels of miRNA-155 in clinical serum samples with
      satisfactory results, suggesting that the proposed sensing platform is promising
      for applications in disease diagnosis as well as the fundamental research of
      biochemistry.

PMID- 29198111
TI  - Expansion of the Genetic Alphabet: A Chemist's Approach to Synthetic Biology.
AB  - The information available to any organism is encoded in a four nucleotide, two
      base pair genetic code. Since its earliest days, the field of synthetic biology
      has endeavored to impart organisms with novel attributes and functions, and
      perhaps the most fundamental approach to this goal is the creation of a fifth and
      sixth nucleotide that pair to form a third, unnatural base pair (UBP) and thus
      allow for the storage and retrieval of increased information. Achieving this
      goal, by definition, requires synthetic chemistry to create unnatural nucleotides
      and a medicinal chemistry-like approach to guide their optimization. With this
      perspective, almost 20 years ago we began designing unnatural nucleotides with
      the ultimate goal of developing UBPs that function in vivo, and thus serve as the
      foundation of semi-synthetic organisms (SSOs) capable of storing and retrieving
      increased information. From the beginning, our efforts focused on the development
      of nucleotides that bear predominantly hydrophobic nucleobases and thus that pair
      not based on the complementary hydrogen bonds that are so prominent among the
      natural base pairs but rather via hydrophobic and packing interactions. It was
      envisioned that such a pairing mechanism would provide a basal level of
      selectivity against pairing with natural nucleotides, which we expected would be
      the greatest challenge; however, this choice mandated starting with analogs that
      have little or no homology to their natural counterparts and that, perhaps not
      surprisingly, performed poorly. Progress toward their optimization was driven by
      the construction of structure-activity relationships, initially from in vitro
      steady-state kinetic analysis, then later from pre-steady-state and PCR-based
      assays, and ultimately from performance in vivo, with the results augmented three
      times with screens that explored combinations of the unnatural nucleotides that
      were too numerous to fully characterize individually. The structure-activity
      relationship data identified multiple features required by the UBP, and perhaps
      most prominent among them was a substituent ortho to the glycosidic linkage that
      is capable of both hydrophobic packing and hydrogen bonding, and nucleobases that
      stably stack with flanking natural nucleobases in lieu of the potentially more
      stabilizing stacking interactions afforded by cross strand intercalation. Most
      importantly, after the examination of hundreds of unnatural nucleotides and
      thousands of candidate UBPs, the efforts ultimately resulted in the
      identification of a family of UBPs that are well recognized by DNA polymerases
      when incorporated into DNA and that have been used to create SSOs that store and
      retrieve increased information. In addition to achieving a longstanding goal of
      synthetic biology, the results have important implications for our understanding
      of both the molecules and forces that can underlie biological processes, so long
      considered the purview of molecules benefiting from eons of evolution, and
      highlight the promise of applying the approaches and methodologies of synthetic
      and medical chemistry in the pursuit of synthetic biology.

PMID- 29198112
TI  - Probing Intermolecular Vibrational Symmetry Breaking in Self-Assembled Monolayers
      with Ultrahigh Vacuum Tip-Enhanced Raman Spectroscopy.
AB  - Ultrahigh vacuum tip-enhanced Raman spectroscopy (UHV-TERS) combines the atomic
      scale imaging capability of scanning probe microscopy with the single-molecule
      chemical sensitivity and structural specificity of surface-enhanced Raman
      spectroscopy. Here, we use these techniques in combination with theory to reveal
      insights into the influence of intermolecular interactions on the vibrational
      spectra of a N-N'-bis(2,6-diisopropylphenyl)-perylene-3,4:9,10-bis(dicarboximide)
      (PDI) self-assembled monolayer adsorbed on single-crystal Ag substrates at room
      temperature. In particular, we have revealed the lifting of a vibrational
      degeneracy of a mode of PDI on Ag(111) and Ag(100) surfaces, with the most
      strongly perturbed mode being that associated with the largest vibrational
      amplitude on the periphery of the molecule. This work demonstrates that UHV-TERS
      enables direct measurement of molecule-molecule interaction at nanoscale. We
      anticipate that this information will advance the fundamental understanding of
      the most important effect of intermolecular interactions on the vibrational modes
      of surface-bound molecules.

PMID- 29198113
TI  - Characterization of Chlamydomonas reinhardtii Core Histones by Top-Down Mass
      Spectrometry Reveals Unique Algae-Specific Variants and Post-Translational
      Modifications.
AB  - The unicellular microalga Chlamydomonas reinhardtii has played an instrumental
      role in the development of many new fields (bioproducts, biofuels, etc.) as well
      as the advancement of basic science (photosynthetic apparati, flagellar function,
      etc.). Chlamydomonas' versatility ultimately derives from the genes encoded in
      its genome and the way that the expression of these genes is regulated, which is
      largely influenced by a family of DNA binding proteins called histones. We
      characterize C. reinhardtii core histones, both variants and their post
      translational modifications, by chromatographic separation, followed by top-down
      mass spectrometry (TDMS). Because TDMS has not been previously used to study
      Chlamydomonas proteins, we show rampant artifactual protein oxidation using
      established nuclei purification and histone extraction methods. After addressing
      oxidation, both histones H3 and H4 are found to each have a single polypeptide
      sequence that is minimally acetylated and methylated. Surprisingly, we uncover a
      novel monomethylation at lysine 79 on histone H4 present on all observed
      molecules. Histone H2B and H2A are found to have two and three variants,
      respectively, and both are minimally modified. This study provides an updated
      assessment of the core histone proteins in the green alga C. reinhardtii by top
      down mass spectrometry and lays the foundation for further investigation of these
      essential proteins.

PMID- 29198114
TI  - Cooperative Electrocatalytic O2 Reduction Involving Co(salophen) with p
      Hydroquinone as an Electron-Proton Transfer Mediator.
AB  - The molecular cobalt complex, Co(salophen), and para-hydroquinone (H2Q) serve as
      effective cocatalysts for the electrochemical reduction of O2 to water.
      Mechanistic studies reveal redox cooperativity between Co(salophen) and H2Q. H2Q
      serves as an electron-proton transfer mediator (EPTM) that enables
      electrochemical O2 reduction at higher potentials and with faster rates than is
      observed with Co(salophen) alone. Replacement of H2Q with the higher-potential
      EPTM, 2-chloro-H2Q, allows for faster O2 reduction rates at higher applied
      potential. These results demonstrate a unique strategy to achieve improved
      performance with molecular electrocatalyst systems.

PMID- 29198115
TI  - Effects of Salt-Controlled Self-Assembly of Triblock Copolymers F68 on
      Interaction Forces between Oil Drops in Aqueous Solution.
AB  - Nonionic triblock copolymers, surfactant Pluronic F68 (PEO76-PPO29-PEO76), are
      widely used in industrial processes, such as foaming, emulsification, and
      stabilization. The behaviors of triblock copolymers such as the salt-dependent
      self-assembly in bulk solution and the irreversible adsorption at the oil/water
      interface are mainly focused to explore their effects on the interaction forces
      between nano-spacing interfaces of oil droplets. In this study, the atomic force
      microscopy (AFM) technique was employed to measure the drop interaction forces
      with different F68 bulk concentrations. All selected bulk concentrations (>=100
      MUM) of copolymers can ensure the formation of a stable layer structure of
      stretched polymer chains ("brush") at the oil/water interface, which behaved as a
      mechanical barrier at the interface. This study quantified the forces caused by
      the space hindrance of F68 copolymers both in the bulk phase and at the interface
      of oil/F68 aqueous solution during drop interaction. The effects of monovalent
      electrolyte (NaCl)-induced self-assembly behavior of triblock copolymers F68 in
      bulk solution on drop interaction forces were measured through the AFM technique.

PMID- 29198116
TI  - Characterization and Detection of Erythropoietin Fc Fusion Proteins Using Liquid
      Chromatography-Mass Spectrometry.
AB  - Erythropoietin Fc (EPO-Fc) fusion proteins are potential drug candidates that
      have been designed for the treatment of anemia in humans by stimulating
      erythrocyte production. Such compounds can be considered performance-enhancing
      agents that may be used by athletes in endurance sports. This study describes the
      primary structure of commercially available EPO-Fc based on comprehensive liquid
      chromatography coupled with mass spectrometry (LC-MS) analysis. A bottom-up
      approach and the intact molecular weight (MW) measurement of deglycosylated
      protein and its IdeS proteolytic fractions was used to determine the amino acid
      sequence of EPO-Fc. Using multiple proteases, peptides covering unknown fusion
      breakpoints (spacer peptides) were identified. We demonstrated that "spacer
      peptides" can be used in the determination of EPO-Fc fusion proteins in
      biological samples using common LC-tandem MS methods.

PMID- 29198117
TI  - Controlled Formation of Radial Core-Shell Si/Metal Silicide Crystalline
      Heterostructures.
AB  - The highly controlled formation of "radial" silicon/NiSi  core-shell nanowire
      heterostructures has been demonstrated for the first time. Here, we investigated
      the "radial" diffusion of nickel atoms into crystalline nanoscale silicon pillar
      11 cores, followed by nickel silicide phase formation and the creation of a well
      defined shell structure. The described approach is based on a two-step thermal
      process, which involves metal diffusion at low temperatures in the range of 200
      400  degrees C, followed by a thermal curing step at a higher temperature of 400 
      degrees C. In-depth crystallographic analysis was performed by nanosectioning the
      resulting silicide-shelled silicon nanopillar heterostructures, giving us the
      ability to study in detail the newly formed silicide shells. Remarkably, it was
      observed that the resulting silicide shell thickness has a self-limiting
      behavior, and can be tightly controlled by the modulation of the initial
      diffusion-step temperature. In addition, electrical measurements of the core
      shell structures revealed that the resulting shells can serve as an embedded
      conductive layer in future optoelectronic applications. This research provides a
      broad insight into the Ni silicide "radial" diffusion process at the nanoscale
      regime, and offers a simple approach to form thickness-controlled metal silicide
      shells in the range of 5-100 nm around semiconductor nanowire core structures,
      regardless the diameter of the nanowire cores. These high quality Si/NiSi core
      shell nanowire structures will be applied in the near future as building blocks
      for the creation of utrathin highly conductive optically transparent top
      electrodes, over vertical nanopillars-based solar cell devices, which may
      subsequently lead to significant performance improvements of these devices in
      terms of charge collection and reduced recombination.

PMID- 29198118
TI  - Rapid and Quantitative Detection of Vibrio parahemolyticus by the Mixed-Dye-Based
      Loop-Mediated Isothermal Amplification Assay on a Self-Priming
      Compartmentalization Microfluidic Chip.
AB  - Vibrio parahemolyticus (VP) mostly isolated from aquatic products is one of the
      major causes of bacterial food-poisoning events worldwide, which could be reduced
      using a promising on-site detection method. Herein, a rapid and quantitative
      method for VP detection was developed by applying a mixed-dye-loaded loop
      mediated isothermal amplification (LAMP) assay on a self-priming
      compartmentalization (SPC) microfluidic chip, termed on-chip mixed-dye-based LAMP
      (CMD-LAMP). In comparison to conventional approaches, CMD-LAMP was advantageous
      on the limit of detection, which reached down to 1 * 103 CFU/mL in food
      contaminated samples without the pre-enrichment of bacteria. Additionally, as a
      result of the use of a mixed dye and SPC chip, the quantitative result could be
      easily acquired, avoiding the requirement of sophisticated instruments and
      tedious operation. Also, CMD-LAMP was rapid and cost-effective. Conclusively, CMD
      LAMP has great potential in realizing the on-site quantitative analysis of VP for
      food safety.

PMID- 29198119
TI  - Synthesis of Fluorescent Au Nanocrystals-Silica Hybrid Nanocomposite (FLASH) with
      Enhanced Optical Features for Bioimaging and Photodynamic Activity.
AB  - Fluorescent Au nanocrystals (AuNCs)-silica hybrid nanocomposite (FLASH) was
      synthesized by co-condensation of surface-modified AuNCs. Present FLASH
      nanocomposite exhibited four times the enhanced photoluminescence and
      photocatalytic activity compared to single nanocrystals. On the basis of these
      enhanced optical features, we successfully demonstrated in vitro fluorescence
      bioimaging of introduced FLASH to human cervical cancer cell line (HeLa). Beyond
      the confirmation of photocatalytic activity from the photodegradation of
      methylene blue as a model compound, the regional selective photodynamic therapy
      of HeLa cells under UV irradiation was also presented. Taken together the
      enhanced optical features and further potential in theranostic applications, we
      expect that the present FLASH can be a promising tool for nanobiotechnology
      field.

PMID- 29198120
TI  - In Situ Interfacial Conjugation of Chitosan with Cinnamaldehyde during
      Homogenization Improves the Formation and Stability of Chitosan-Stabilized
      Emulsions.
AB  - The emulsifying properties of a natural cationic polysaccharide (chitosan) were
      improved by in situ conjugation with a natural essential oil (cinnamaldehyde, CA)
      during homogenization. In the absence of CA, chitosan-coated medium-chain
      triglyceride droplets were highly susceptible to creaming and coalescence at pH
      values ranging from 1 to 6.5. However, incorporation of relatively low levels of
      CA in the oil phase greatly improved the formation and stability of oil-in-water
      emulsions. These effects were attributed to two main factors: (i) covalent
      binding of lipophilic CA moieties to hydrophilic chitosan chains leading to
      conjugates with a good surface activity and (ii) interfacial cross-linking of
      adsorbed chitosan layers by CA leading to the formation of a rigid polymeric
      coating around the lipid droplets, which improved their stability against
      coalescence. The encapsulation technique developed in this study may be useful
      for applications in a range of commercial products; regulatory and flavor issues
      associated with chitosan and CA would have to be addressed.

PMID- 29198121
TI  - Industry-Academic Collaboration in Oral Biopharmaceutics: The European IMI OrBiTo
      Project.

PMID- 29198122
TI  - Iron deposition in rabbit cerebellum after exposure to generated and mobile GSM
      electromagnetic fields.
AB  - BACKGROUND: Mobile phone application may cause structural, functional changes and
      accumulation of toxic elements in brain. OBJECTIVES: The aim of this study was to
      investigate iron accumulation in rabbit cerebellum after exposure to RF EMF with
      light and scanning electron microscopy. MATERIALS AND METHODS: Histochemical
      analysis of iron distribution by light and electron microscopy with energy
      dispersive microanalysis was used. RESULTS: Light microscopy revealed dystrophic
      changes of Purkinje cells in irradiated groups and iron deposits located in
      various parts of cerebellum. Deposits consists of C, O, Na, Mg, Al, Si, P, S, Cl,
      Ca and Fe. CONCLUSION: Our experiment revealed structural changes of Purkinje
      cells and iron and aluminium accumulations in stratum granulosum of rabbit's
      cerebellum after exposure to RF EMF (Fig. 6, Ref. 33).

PMID- 29198123
TI  - Comparative analysis of human omental milky spots between the patients with colon
      cancer and the control group.
AB  - AIM: Morphological description of milky spots (MSs) in the human greater omentum.
      METHOD: Samples of the greater omentum collected during surgical procedures were
      subjected to further histological analysis. Two groups of patients were studied.
      Group A consisted of patients with colon cancer and peritonitis (stimulated MSs),
      group B consisted of patients without colon cancer and without peritonitis
      (unstimulated MSs). In the research, we focused on the cellular composition and
      differences between stimulated and unstimulated MSs. RESULTS: MSs detected in the
      study were predominantly oval (67 %), round (12 %) or irregular in shape (21 %).
      The average number of immune cells found in one milky spot (MS) in the group A
      was 454 (209-694), consisted of T cells in 44.7 % (27-55 %), B cells in 26.8 %
      (16-34 %), macrophages in 18.3 % (12-27 %) and other immune cells in 10.2 % (6-18
      %). The average number of immune cells found in one MS in the group B was 58 (42
      100 %), consisted of T cells in 21.1 % (16-22 %), B cells in 18.7 % (13-22 %),
      macrophages in 46.9 % (33-60 %) and other immune cells in 13.3 % (1-22 %). The
      average size of MSs in the group A was significantly higher than in the group B:
      768 MUm (313-1075) to 293 MUm (197-421). The results showed that there were
      significant differences in terms of strong predominance of macrophages in
      unstimulated milky spots and strong predominance of T cells in stimulated milky
      spots. CONCLUSION: MSs are specific immune active lymphatic structures on the
      greater omentum. They play a key role in defense mechanism, especially in
      peritonitis. Their function is not completely clear in cancer, some authors
      suggest they might play a significant role in omental metastasis. Further
      analysing of the morphology and cells interactions of MSs is needed (Tab. 2, Fig.
      6, Ref. 20).

PMID- 29198124
TI  - Investigation of the effectiveness of ghrelin treatment in lung tissue of rats
      with sepsis.
AB  - OBJECTIVE: We aimed to investigate the effects of exogenous ghrelin on cytokine
      and ghrelin levels, oxidant parameters, and apoptotic genes in lung tissue during
      sepsis. BACKGROUND: There was evidence that changes of apoptosis are linked with
      morbidity and mortality in sepsis. There were scarce studies on the effect of
      ghrelin on apoptotic genes and endogenous ghrelin levels during sepsis. METHODS:
      Male Wistar albino rats 200-250 g were separated into four groups; Control, LPS
      (5 mg/kg), Ghrelin (10 nmol/kg i.v.), and LPS+Ghrelin. Tumor necrosis factor
      alpha (TNF-alpha), interleukin-10 (IL-10), and ghrelin levels were determined
      from lung tissue using enzyme-linked immunosorbent assay (ELISA). TNF-alpha, IL
      10, Bcl-2, and Bax gene expressions were calculated using quantitative real-time
      polymerase chain reaction (RT-PCR), tissue superoxide dismutase enzyme (SOD)
      activities and malondialdehyde (MDA) were determined spectrophotometerically.
      RESULTS: TNF-alpha levels decreased in the LPS+Ghrelin group compared with the
      LPS (p < 0.001). IL-10 and MDA levels were found highly significantly increased
      in the LPS and LPS+Ghrelin groups (p < 0.05). Tissue SOD activities were higher
      in the Ghrelin and LPS+Ghrelin group compared with the LPS (p < 0.05). TNF-alpha,
      and Bax expression levels were increased in the LPS compared with the other
      groups. IL-10 expression levels were increased in the experimental groups
      compared with the controls. Bcl-2 expression levels were increased in the Ghrelin
      and LPS+Ghrelin compared with other groups. CONCLUSION: Ghrelin treatment
      attenuated LPS-induced lung injury. Treatment with ghrelin had no impact on serum
      and tissue ghrelin levels, but it decreased the level of proinflammatory
      cytokines. We found that ghrelin treatment had an antioxidant effect on SOD
      levels. Also, ghrelin decreased the activity of proapoptotic Bax and increased
      antiapoptotic Bcl-2. Our findings suggest that administration of ghrelin may
      attenuate damage in lung tissue during sepsis (Fig. 4, Ref. 33).

PMID- 29198125
TI  - Comparison between the effect of kartogenin and TGFbeta3 on chondrogenesis of
      human adipose- derived stem cells in fibrin scaffold.
AB  - BACKGROUND: Due to very sluggish turnover at the molecular and cellular level,
      the healing of chondral damages has been considered difficult. In the current
      study, the effects of the Kartogenin, a small heterocyclic molecule on
      chondrogenic differentiation of stem cells was compared to TGF-beta3. METHODS:
      Human Adipose-Derived Stem Cells were extracted during an elective surgery. Cell
      viability was estimated by MTT assay, differentiated cells evaluated by
      histological and immunohistochemical techniques. Expression of cartilage specific
      genes (SOX9, Aggrecan, type II and X collagens) assessed by real-time PCR.
      RESULTS: The real-time PCR assay has revealed the expression of gene marker of
      chondrogenesis, SOX9, Aggrecan and type II collagen, both in Kartogenin and
      TGFbeta3 groups compared to the control group, significantly (p < 0.05). A low
      expression level of collagen type X as a hypertrophic marker was seen in
      cartilage produced by using Kartogenin. Meanwhile, the level of type X collagen
      protein in Kartogenin group was significantly decreased (p > 0.05) compared to
      TGF-beta3 group. CONCLUSION: Kartogenin was suitable for successful chondrogenic
      differentiation of human adipose- derived stem cells and a suppressor of the
      consequent hypertrophy (Tab. 1, Fig. 5, Ref. 31).

PMID- 29198126
TI  - Effect of lipopolysaccharide on toll-like receptor-4 signals in mouse cancer
      cells.
AB  - BACKGROUND: Recent findings showed that activated TLR signals on cancer cells
      might promote cancer progression. This study was designed to explore the
      influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on
      mouse melanoma and breast cancer cell proliferation and their TLR4 signalling.
      METHODS: Mouse melanoma cell line (B16F10) and breast cancer cell line (4T1) were
      taken as models. They were treated with LPS (0, 1.25, 2.5, 5, 7.5, 10 ug/ml) for
      4, 16, 24, 48 h and MTT assay was done. The expression of TLR4, MyD88, NF-kappaB
      mRNA was detected by quantitative real time-polymerase chain reaction method
      quantitatively. RESULTS: Ultra-pure LPS at 5 ug/ml concentration increased
      significantly B16F10 cell viability 24 hour after stimulation, but not in 4T1
      cell. The mRNA levels of TLR4, MyD88 and NF-kappaB were significantly up
      regulated in both cell lines by stimulating the cells at 5 ug/ml LPS.
      CONCLUSIONS: Our data demonstrated that B16F10 and 4T1 cells are responsive to
      LPS, but their responses are time and dose dependent. These results provide new
      ways to understand the TLR4 signalling in tumour cells (Fig. 2, Ref. 24).

PMID- 29198127
TI  - Immunohistochemical investigation of P16, P53 and Ki-67's prognostic values in
      diffuse large B-Cell lymphomas.
AB  - AIM: The aim of this study is to determine the immunohistochemical properties of
      Ki-67, P53 expression and loss of P16, and to assess their relationship with both
      clinical parameters and patient survival in DLBCL. METHOD: Forty patients,
      diagnosed at the Pathology Department of our institute with nodal DLBCL were
      selected as the study group. The relationship between P16, P53, Ki-67 expressions
      and clinical and laboratory parameters like age, gender, performance status,
      Eastern Cooperative Oncology Group (ECOG), clinical stage, presence of B
      symptoms, bone marrow involvement, International Prognostic Index (IPI) score,
      lactate dehydrogenase (LDH) level, extranodal extension, relapse, C-reactive
      protein (CRP), sedimentation, number of leukocytes in patients and patient
      survival were then statistically evaluated. RESULTS: Our results display no
      statistically significant correlation between P53 expression and loss of P16, Ki
      67 proliferation index and clinical parameters and overall survival (p > 0.05).
      The only statistically significant relationship was between loss of P16 and stage
      (p 0.05). CONCLUSION: According to the results of our study, the loss of P16, P53
      gene expression and Ki-67 proliferation index have no effect on life expectancy
      of patients with DLBCL (Tab. 2, Fig. 2, Ref. 29).

PMID- 29198128
TI  - Proprotein convertase 1 mediated proneuropeptide proteolytic processing in
      ischemic neuron injury.
AB  - BACKGROUND: Pro-protein processing mechanism plays an important role in neuron
      injury. OBJECTIVE: To study the protein convertase 1 (PC1) mediated processing
      mechanism, the ischemic cellular or tissue proPC1/PC1 or proCgA/CgA (pro
      chromogranin A) was analyzed. METHODS: NS20Y differentiated cells were stressed
      by 0-6 h of oxygen and glucose deprivation (OGD) in glucose-free DMEM and an
      anaerobic jar environment. Ischemic C57BL/J mouse model was established by
      performing 60-min of middle cerebral artery occlusion (MCAO) operation and
      subsequent 4 or 24-h reperfusion. The TUNEL, immunochemistry, and Western blot
      methods were used to detect protein expression in ischemic cells or tissues.
      RESULTS: The OGD or MCAO stress caused substantial cell death in a dose-dependent
      manner (p < 0.05 or 0.01). With the increasing OGD dose, proPC1 and PC1 proteins
      gradually increased (p < 0.05 or 0.01) whereas proCgA and CgA proteins decreased
      (p < 0.05). In vivo the proPC1 and PC1 expressions presented with a peak at 4-h
      and then decreased at 24-h reperfusion (p < 0.05 or 0.01). The tissue proCgA and
      CgA proteins decreased with the increasing reperfusion time (p < 0.05).
      CONCLUSIONS: The results suggest that the increasing PC1 expression promoted the
      transformation of proCgA into CgA or smaller peptides, i.e. Pancreastatin or
      Secretoneurin, and the PC1 mediated processing plays a critical role (Fig. 4,
      Ref. 15).

PMID- 29198129
TI  - Hemodynamic effects of epinephrine in rats: evaluation by impedance cardiography.
AB  - BACKGROUND AND OBJECTIVES: This study was aimed to examine how inotropic effects
      of intravenously injected epinephrine change thoracic impedance measurements and
      to reveal the possible effects of this change on other hemodynamic parameters by
      using the technique of impedance cardiography. METHODS: 10 male Wistar Albino
      rats were divided into two equal groups: control and epinephrine. 0.2 mg/kg of
      epinephrine was administered to the rats in the epinephrine group via the tail
      vein. All hemodynamic parameters obtained by impedance cardiography [the base
      impedance (Z0), the maximum rate of change in impedance (dZmax/dt), the left
      ventricular ejection time (LVET), stroke volume (SV), cardiac output (CO),
      contractility index (IC), thoracic fluid content (TFC), heart rate (HR)] were
      recorded using the EBI 100C, DA 100 and ECG modules in the BIOPAC MP100 system.
      RESULTS: CO (p <= 0.05), HR (p <= 0.001), dZmax/dt (p <= 0.05) and IC (p <= 0.05)
      increased statistically significantly in the epinephrine group compared to the
      control group. However, LVET (p <= 0.001) decreased statistically significantly
      in the epinephrine group compared to the control group. CONCLUSION: Tachycardia
      was detected in the epinephrine group. There was an inverse correlation between
      LVET and dZmax/dt and IC. This is based on the fact that epinephrine increases
      inotropic effect (Tab. 2, Fig. 4, Ref. 30).

PMID- 29198130
TI  - The protective effect of thymoquinone over olanzapine-induced side effects in
      liver, and metabolic side effects.
AB  - OBJECTIVES: The aim of the study was to investigate the possible protective
      qualities of thymoquinone (TQ) against the side-effects of olanzapine (OLZ) in an
      experimental model in rat liver with histologic and biochemical assessments.
      METHODS: Experimental procedures were performed on 35 female Sprague Dawley rats.
      Rats were randomly divided into five groups as: group 1: control; group 2: OLZ;
      group 3: OLZ+TQ-1; group 4: OLZ+TQ-2; and group 5: OLZ+TQ-3. RESULTS: The results
      showed that a 2-week administration of OLZ (4 mg/kg, once a day for the first
      week, 8 mg/kg once a day for the second week, p.o.) and treatment with TQ (25,
      50, 100 mg/kg, once daily, p.o.) significantly reduced weight gain induced by
      OLZ. In addition, TQ increased the total antioxidant status (TAS), high-density
      lipoprotein cholesterol (HDL), insulin levels and decreased serum oxidative
      stress index (OSI), total oxidant status (TOS), alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), low
      density lipoprotein cholesterol (LDL), glucose, triglycerides (TG) and total
      cholesterol (CH) levels significantly (p < 0.05). CONCLUSION: This study revealed
      that treatment with TQ might protect liver tissue against the side-effects of
      OLZ. TQ could be an effective course of therapy to enhance therapeutic efficacy
      (Tab. 4, Fig. 4, Ref. 47).

PMID- 29198131
TI  - Early detection of cardiac surgery-associated acute kidney injury by microRNA-21.
AB  - We tested the hypothesis whether microRNA-21 (miR-21) can detect CSA-AKI earlier
      than serum creatinine (sCr). A total of 103 patients scheduled to undergo cardiac
      surgery. CSA-AKI was defined as sCr > 0.3 mg/dl 24 h after surgery. The patients
      were divided into two groups according to whether or not developing AKI after
      surgery. Serum and urinary miR-21 were measured prior to, and 6, 12 and 24 h
      after surgery. Baseline serum and urinary levels of miR-21 in AKI group were
      lower than in non-AKI group. Moreover, the levels of miR-21 were significantly
      lower 6 h after surgery for serum, and 6 and 12 h after surgery for urine samples
      than those before surgery in AKI group. Area under the curve (AUC) of the
      receiver operating characteristic (ROC) values were 0.81 (95% CI: 0.65-0.97) for
      serum miR-21 (6 h after surgery), 0.90 (95% CI: 0.79-0.99) for urine (6 h after
      surgery), and 0.86 (95% CI: 0.71-0.98) for urine (12 h after surgery). While both
      postoperative serum and urinary miR-21 levels can predict AKI development,
      urinary miR-21 especially 6 h after surgery is a more reliable marker than serum
      miR-21 for detection of established CSA-AKI (Tab. 1, Fig. 3, Ref. 43).

PMID- 29198132
TI  - MEG3 long non-coding RNA prevents cell growth and metastasis of osteosarcoma.
AB  - OBJECTIVE: This study aimed to investigate the role of long non-coding RNA MEG3
      (lncRNA MEG3) in osteosarcoma (OS) and further explore the underlying molecular
      mechanism. MATERIALS AND METHODS: The expression profiles of MEG3 in OS cell
      lines and normal osteoblast cell line were detected by qRT-PCR. MEG3 was over
      expressed in OS cell line by using LV-MEG3. MTT and colony-formation assays were
      applied for cell proliferation analysis. Cell migration assay was applied to
      investigate the cell migration ability. In addition, the expression levels of
      cell growth and metastasis related factors (Notch1, Hes1, TGF-beta, N-cadheren
      and E-cadheren) were determined to illustrate the mechanisms. RESULTS: We found
      that compared with normal osteoblast hFOB1.19 cell line, MEG3 was significantly
      down-regulated in MG63 and U2OS cell lines, particularly in MG-63 cells. MEG3 was
      significantly up-regulated in MG63 cells by LV-MEG3. Cell proliferation and
      migration ability were obviously repressed by MEG3 over-expression. In addition,
      MEG3 over-expression markedly inhibited Notch1, Hes1,TGF-beta and N-cadheren
      expression, and the expression level of E-cadheren was improved. CONCLUSIONS:
      These results indicated that MEG3 could prevent cell growth and metastasis of OS
      by repressing Notch and TGF-beta signaling pathway, thus providing a potential
      therapeutic target for OS treatment (Tab. 1, Fig. 4, Ref. 30).

PMID- 29198133
TI  - FOXP3, RORgammat and IL-10 cytokine profile in chronic heart failure.
AB  - BACKGROUND: Distinct subsets of T cells play crucial regulatory roles in
      inflammatory processes of chronic heart failure (CHF). Retinoic acid receptor
      related orphan receptor-gammat (Ror-gammat) and Forkhead box P3 (Foxp3) have been
      defined as the "master regulators" of Th17 cells and Treg cells, respectively. At
      the same time, anti-inflammatory cytokines such as IL-10 may neutralize
      inflammation in CHF. The current study was designed to compare FOXP3, RORgammat
      and IL-10 protein expression in the blood and IL-10 in supernatant PBMCs in CHF
      patients versus normal subjects. PATIENTS AND METHODS: Our study population
      consisted of 42 patients with CHF in four different function classes and 42
      healthy subjects who served as controls. RNA extraction and cDNA synthesis was
      performed and mRNA expression for genes FOXP3, RORgammat, IL-10 was determined by
      RT-PCR. The amount of IL-10 protein in supernatant of PBMCs was measured by ELISA
      technique. RESULTS: There was no significant difference in FOXP3, RORgammat, IL
      10 protein expression and supernatant PBMCs IL-10 in CHF patients as compared to
      control. The level of Foxp3 was significantly lower in CHF patients with ischemic
      vs non-ischemic cause (p = 0.04). DISCUSSION: Although inflammation plays a
      central role in the pathophysiology of CHF, the roles of FOXp3, RORgammat, and IL
      10 remain to be determined (Tab. 3, Ref. 33).

PMID- 29198134
TI  - If We Build It, Will They Come? Perceptions of HIV Cure-Related Research by
      People Living with HIV in Four U.S. Cities: A Qualitative Focus Group Study.
AB  - Global interest and investment in the search for an HIV cure has increased.
      Research has focused on what experts refer to as a sterilizing or eradicating
      cure, where HIV is eliminated from the body, and on what is often called a
      functional cure, where HIV remains, kept durably suppressed in the absence of
      antiretroviral treatment and therapy (ART). Many believe that a functional cure
      is likely to be found first. HIV cure studies will require active participation
      by people living with HIV (PLWHIV). Their desires and perceptions will be
      important to effectively recruit study participants and for the uptake of any
      future strategy that demonstrates safety and efficacy. The perspectives of PLWHIV
      are essential to advancing HIV cure research, and they should be taken into
      consideration as biomedical research advances. We conducted 10 focus groups in
      four U.S. cities, eliciting perspectives of PLWHIV on HIV cure and cure research.
      Most participants conceived of a cure as eradicating, and felt favorably toward
      it. In addition to the physical benefits of a potential cure, participants valued
      the possible de-stigmatization related to no longer living with HIV, liberation
      from concerns about transmitting HIV, and freedom from the burden of daily
      medication. Many participants did not regard a functional cure as an improvement
      over controlling HIV through ART, were distrustful about viral rebound potential,
      and noted concerns about medical complications and accompanying psychological
      distress. Some felt that the risks of HIV cure research were not worth taking.
      Many were skeptical about science's ability to eliminate HIV from the body.

PMID- 29198135
TI  - Tissue Inhibitor of Metalloproteinase-3 Promotes Schwann Cell Myelination.
AB  - Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activities of
      various metalloproteinases including matrix metalloproteinases and ADAM family
      proteins. In the peripheral nervous system, ADAM17, also known as TNF-alpha
      converting enzyme (TACE), cleaves the extracellular domain of Nrg1 type III, an
      axonal growth factor that is essential for Schwann cell myelination. The
      processing by ADAM17 attenuates Nrg1 signaling and inhibits Schwann cell
      myelination. TIMP-3 targets ADAM17, suggesting a possibility that TIMP-3 may
      elicit a promyelinating function in Schwann cells by relieving ADAM17-induced
      myelination block. To investigate this, we used a myelinating coculture system to
      determine the effect of TIMP-3 on Schwann cell myelination. Treatment with TIMP-3
      enhanced myelin formation in cocultures, evident by an increase in the number of
      myelin segments and upregulated expression of Krox20 and myelin protein. The
      effect of TIMP-3 was accompanied by the inhibition of ADAM17 activity and an
      increase in Nrg1 type III signaling in cocultures. Accordingly, the N-terminus
      fragment of TIMP-3, which exhibits a selective inhibitory function toward ADAM17,
      elicited a similar myelination-promoting effect and increased Nrg1 type III
      activity. TIMP-3 also enhanced laminin production in cocultures, which is likely
      to aid Schwann cell myelination.

PMID- 29198136
TI  - Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the
      Brain.
AB  - High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk
      factor for vascular cognitive impairment and dementia, which is the second
      leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages
      and cognitive decline in mice, the specific effect of hyperhomocysteinemia on
      each cell type remains unknown. We took separate cultures of astrocytes,
      microglia, endothelial cells, and neuronal cells and treated each with moderate
      levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene
      expression changes for cell-specific markers and neuroinflammatory markers
      including the matrix metalloproteinase 9 system. Astrocytes had decreased levels
      of several astrocytic end feet genes, such as aquaporin 4 and an adenosine
      triphosphate (ATP)-sensitive inward rectifier potassium channel at 72 hr, as well
      as an increase in matrix metalloproteinase 9 at 48 hr. Gene changes in microglia
      indicated a peak in proinflammatory markers at 48 hr followed by a peak in the
      anti-inflammatory marker, interleukin 1 receptor antagonist, at 72 hr.
      Endothelial cells had reduced occludin expression at 72 hr, while kinases and
      phosphatases known to alter tau phosphorylation states were increased in neuronal
      cells. This suggests that hyperhomocysteinemia induces early proinflammatory
      changes in microglia and astrocytic changes relevant to their interaction with
      the vasculature. Overall, the data show how hyperhomocysteinemia could impact
      Alzheimer's disease and vascular cognitive impairment and dementia.

PMID- 29198137
TI  - A cross-sectional survey of cardiovascular health and lifestyle habits of
      hospital staff in the UK: Do we look after ourselves?
AB  - Background A high prevalence of stress-related disorders is well known among
      healthcare professionals. We set out to assess the prevalence of cardiovascular
      risk factors and compliance with national dietary and physical activity
      recommendations in NHS staff in the UK with comparison between clinical and non
      clinical staff, and national surveys. Design A multi-centre cross-sectional
      study. Methods A web-based questionnaire was developed to include anonymised data
      on demographics, job role, cardiovascular risk factors and diseases, dietary
      habits, physical activity and barriers towards healthy lifestyle. This was
      distributed to staff in four NHS hospitals via emails. Results A total of 1158
      staff completed the survey (response rate 13%) with equal distribution between
      the clinical and non-clinical groups. Most staff were aged 26-60 years and 79%
      were women. Half of the staff were either overweight or obese (51%) with no
      difference between the groups ( P = 0.176), but there was a lower prevalence of
      cardiovascular risk factors compared to the general population. The survey
      revealed a low compliance (17%) with the recommended intake of five-a-day
      portions of fruit and vegetables, and that of moderate or vigorous physical
      activity (56%), with no difference between the clinical and non-clinical staff (
      P = 0.6). However, more clinical staff were exceeding the alcohol recommendations
      ( P = 0.02). Lack of fitness facilities and managerial support, coupled with long
      working hours, were the main reported barriers to a healthy lifestyle.
      Conclusions In this survey of UK NHS staff, half were found to be overweight or
      obese with a lower prevalence of cardiovascular risk factors compared to the
      general population. There was a low compliance with the five-a-day fruit and
      vegetables recommendation and physical activity guidelines, with no difference
      between the clinical and non-clinical staff.

PMID- 29198138
TI  - Post-traumatic stress disorder symptoms and aversive cognitions regarding
      physical activity in patients evaluated for acute coronary syndrome.

PMID- 29198139
TI  - Evaluation of the coronary flow by the coronary clearance time in patients with
      cardiac syndrome X.
AB  - Objective The vessels involved in the microcirculation are too small to be
      visualized by conventional angiography and no tools are currently available that
      can directly evaluate the coronary microcirculation. This study evaluated the
      coronary clearance frame count (CCFC) in patients with cardiac syndrome X (CSX).
      Methods The retrospective study enrolled patients with angina, who had a positive
      nuclear imaging test and normal coronary angiography; and a control group
      consisting of patients who underwent an angiogram to exclude coronary artery
      disease. Thrombosis in myocardial infarction frame count (TFC) and CCFC for each
      coronary artery (left anterior descending coronary artery [LAD], circumflex
      coronary artery [CFX] and right coronary artery [RCA]) were calculated offline.
      Results A total of 71 patients with CSX and 61 control patients were enrolled in
      the study. No significant differences were found between the two groups regarding
      the baseline demographic and clinical variables. The TFC of LAD, CFX and RCA were
      similar between the two groups. The mean CCFC-LAD, CCFC-CFX and CCFC-RCA were
      significantly longer in the CSX group compared with the control group. Conclusion
      CCFC is a simple, quantitative and highly reproducible method that might be used
      as a marker of coronary microvascular dysfunction.

PMID- 29198140
TI  - Development of stabilized tenofovir disoproxil tablet: degradation profile,
      stabilization, and bioequivalence in beagle dogs.
AB  - The purpose of this study was to develop a hydrolysis-resistant optimized oral
      formulation of tenofovir disoproxil (TD) using a stabilizer. To develop a
      stabilized TD tablet bioequivalent to the commercial TD fumarate (TDF, Viread(r))
      tablet, TD free base was prepared and its degradation profile and stability were
      investigated. The TD tablet showed antiviral activity, but its absorption was
      limited in the intestinal tract because of premature degradation. The drug
      subjected to severe conditions for the stress test was catalyzed under neutral,
      basic, oxidative, and thermolytic conditions, whereas it was comparatively stable
      under acidic, photolytic, and humid states. The compatibility study showed that
      sodium bisulfite (SB) stabilized TD by preventing its degradation in aqueous and
      3% peroxide solutions compared with the unstabilized TD. According to the
      stability analysis and degradation profile, four TD tablet formulations were
      prepared. The selected TD tablets were composed of non-hygroscopic excipients
      (lipophilic-fumed silica, anhydrous lactose, and microcrystalline cellulose
      [MCC]), SB, croscarmellose sodium (CCS), and hydrogenated castor oil (HCO), and
      were manufactured using a dry granulation method because of their hydrolytic
      properties. The stabilized TD tablet showed similar dissolution properties as the
      TDF (Viread(r)) reference tablet in pH 1.2, 4.0, and 6.8 and water. Moreover, the
      lower degradation rate of the tablet in simulated gastrointestinal fluid
      demonstrated that its intestinal absorption might have improved owing to
      prevention of its enzymatic hydrolysis and the pH effect. Finally, the formulated
      TD tablet was bioequivalent to the TDF (Viread(r)) reference tablet in beagle
      dogs.

PMID- 29198141
TI  - Association Between Plantar Fasciitis and Isolated Gastrocnemius Tightness.
AB  - BACKGROUND: An association between plantar fasciitis and isolated gastrocnemius
      tightness (IGT) has been postulated in the literature; however, there have been
      few studies to prove this relationship. This prospective cross-sectional cohort
      study was aimed at determining the association between plantar fasciitis and IGT.
      METHODS: Three groups comprising 45 patients with plantar fasciitis (group 1),
      117 patients with foot and ankle pathology other than plantar fasciitis (group
      2), and 61 patients without foot and ankle pathology (group 3) were examined for
      the presence of IGT using the Silfverskiold test. Statistical tests included chi
      square test, Student t test, and analysis of variance. RESULTS: Of the patients,
      101 (45.3%) had IGT: 36 (80%) in group 1, 53 (45.3%) in group 2, and 12 (19.7%)
      in group 3. The difference in IGT prevalence between the groups was statistically
      significant at P < .001. The prevalence of IGT was similar between acute and
      chronic plantar fasciitis at 78.9% and 80.6%, respectively. CONCLUSION: There was
      a very strong association between plantar fasciitis and IGT using group 3 as a
      reference. This study suggests that IGT should be actively sought out and managed
      in patients with plantar fasciitis. LEVEL OF EVIDENCE: Level II, cross-sectional
      cohort prospective study.

PMID- 29198142
TI  - Comparison of Intercuneiform 1-2 Joint Mobility Between Hallux Valgus and Normal
      Feet Using Weightbearing Computed Tomography and 3-Dimensional Analysis.
AB  - BACKGROUND: An association has been reported between hallux valgus and
      hypermobility of the first ray, but subluxation of the intercuneiform 1-2 joint
      was also suspected in some cases. However, dynamics of the intercuneiform 1-2
      joint has seldom been investigated. This study used weightbearing computed
      tomography (CT) and a 3-dimensional (3D) analysis system to evaluate displacement
      of the intercuneiform 1-2 joint, intercuneiform 2-3 joint, and second
      cuneonavicular joint due to weightbearing in hallux valgus and normal feet.
      METHODS: Patients were 11 women with hallux valgus (mean age, 56 years; mean
      hallux valgus angle, 43 degrees; mean first-second intermetatarsal angle, 22
      degrees) and 11 women with normal feet (mean age, 57 years; mean hallux valgus
      angle, 14 degrees; mean first-second intermetatarsal angle, 9 degrees). Each
      patient was placed supine with the lower limbs extended, and CT was performed
      under nonweightbearing and weightbearing conditions (load equivalent to body
      weight). 3D models reconstructed from CT images were used to compare displacement
      of the intermediate cuneiform relative to the medial cuneiform under
      nonweightbearing and weightbearing conditions. RESULTS: Relative to the medial
      cuneiform, the middle cuneiform was displaced by 0.1 and 0.8 degrees due to
      dorsiflexion, 0.2 and 1.0 degrees due to inversion, and 0.7 and 0.7 degrees due
      to abduction in normal feet and feet with hallux valgus, respectively, with the
      latter having significantly greater dorsiflexion ( P = .0067) and inversion ( P =
      .0019). There was no significant intergroup difference at the intercuneiform 2-3
      joint and second cuneonavicular joint. CONCLUSION: This study clarified the
      detailed load-induced displacement of the cuneiform 3-dimensionally. Compared
      with normal feet, hallux valgus feet had significantly greater mobility of the
      intercuneiform 1-2 joint, suggesting hypermobility of this joint. LEVEL OF
      EVIDENCE: Level III, case-control study.

PMID- 29198143
TI  - EBV+ HHV-8+ Multicentric Castleman Disease With Plasmablastic Aggregates in an
      HIV+ Man: An Evolving Clinicopathologic Entity.
AB  - We report a case of EBV+ and HHV-8+ multicentric Castleman disease with
      plasmablastic aggregates in an HIV-positive individual. A 41-year-old man
      presented in early 2015 with fevers, sweats, weight loss, intractable itching,
      and on subsequent testing was found to be HIV positive. Investigations showed
      cervical lymphadenopathy and splenomegaly. He was treated for HIV and his
      symptoms resolved. His symptoms recurred in January 2016, and a provisional
      diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human
      herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left
      supraclavicular lymph node core biopsy was performed, which showed features of
      multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER)
      and HHV-8 positive. He responded well to rituximab treatment and remains well
      with no symptoms at recent follow-up.

PMID- 29198144
TI  - The Great Imitator: Syphilis Presenting as an Inflammatory Pseudotumor of Liver.

PMID- 29198145
TI  - Pleomorphic Lobular Carcinoma: A Controversially Aggressive Variant of Invasive
      Lobular Carcinoma of the Breast.

PMID- 29198146
TI  - Salvage stereotactic radiosurgery for recurrent gliomas with prior radiation
      therapy.
AB  - This study aims to assess the viability of salvage stereotactic radiosurgery
      (SRS) for recurrent malignant gliomas through assessing overall survival, local
      control and toxicity. We performed a retrospective review of 65 patients with 76
      lesions (55 high-grade, 21 low-grade) treated with salvage SRS between 2002 and  
      2012. Median follow-up from salvage SRS was 14.9 months (IQR: 0.9-28.1), 8.3
      months (IQR: 4.0-13.3) and 8.5 months (IQR: 3.9-15.8) for low-grade, high-grade,
      and combined, respectively. A 12-month overall survival from salvage SRS was
      68.4, 38.7 and 47.3% for low-grade, high-grade and combined respectively. A total
      of 6-month local control was 86.2, 53.8 and 65.3% for low-grade, high-grade and
      combined, respectively. Our results indicate salvage SRS can provide acceptable
      survival and local control with minimal toxicity.

PMID- 29198147
TI  - Optimisation of beta-cyclodextrin inclusion complexes with natural antimicrobial
      agents: thymol, carvacrol and linalool.
AB  - Beta-cyclodextrin (beta-CD) inclusion complexes with naturally derived
      antimicrobial (AM) agents: thymol, carvacrol and linalool were prepared using a
      co-precipitation technique. Conditions including solvent composition,
      temperature, reaction time and total solvent volume were investigated to optimise
      the inclusion efficiency (IE) and yield. Electrospray ionisation mass
      spectrometry was used to confirm the formation of the thymol/beta-CD complex and
      gas chromatography was used to quantify the amount AM agent that was
      encapsulated, absorbed onto the surface, or remaining in the filtered solvent.
      The systematic optimisation of the conditions improved both the yield of the
      complex and the IE of the AM agents compared to previously reported methods that
      have been applied to other agents. Using a 1:1 mole ratio of the AM agent to beta
      CD, the optimised parameters resulted in maximum yields of 87, 84 and 86% (w/w)
      for thymol, carvacrol and linalool, respectively, with IE's close to 100% (w/w)
      for each agent.

PMID- 29198148
TI  - US human factors engineering evaluation of an updated follitropin alfa pen
      injector (GONAL-f(r) RFF Redi-ject(r)) and instructions for use.
AB  - OBJECTIVES: The multi-dose, pre-filled GONAL-f(r) RFF Redi-ject(r) (follitropin
      alfa injection) pen injector was updated following feedback on user experience
      and pen functionality, as part of a continuous assessment program. Human-factors
      engineering (HFE) evaluations were conducted to confirm that the updated pen
      injector could be used by intended users to safely and effectively perform
      critical tasks identified by the risk-management plan. METHODS: Five rounds of
      formative evaluation and a simulated-use summative evaluation of the pen
      injector, instructions for use (IFU), and training video were conducted by HFE
      specialists or the intended users of the pen injector. RESULTS: The IFU and
      training video were revised following formative evaluations. Summative evaluation
      of simulated-use involved 60 participants, each of whom performed six use
      scenarios related to potential hazards, selected on the basis of the risk
      management plan. Overall, participants found the pen injector easy to use and the
      IFU clear and effective. CONCLUSIONS: Through an iterative process involving a
      series of HFE evaluations, modifications were made to the injection mechanism,
      the dose display, the IFU and the training video. Summative evaluation confirmed
      that the updated pen injector and associated user materials can be used safely
      and effectively to perform critical tasks identified through the risk-management
      plan.

PMID- 29198149
TI  - Correction to: Tan et al., Recent developments in D-alpha-tocopheryl polyethylene
      glycol-succinate-based nanomedicine for cancer therapy.

PMID- 29198151
TI  - Validation of the 8th AJCC staging system for gastric cancer in a population
      based setting.
AB  - BACKGROUND: The aim of this analysis is to validate the prognostic value of the
      8th edition of the American Joint Committee on Cancer (AJCC) staging system for
      gastric cancer. METHODS: Through SEER*Stat program, Surveillance, epidemiology
      and end results database (2010-2013) was accessed and 8th AJCC stages were
      reconstructed. Cancer-specific survival analyses according to both 7th and 8th
      editions were conducted through Kaplan-Meier analysis/log-rank testing and
      multivariate analysis was conducted through a Cox model. RESULTS: Among
      pathologically-staged patients, P values for pairwise comparisons among different
      8th AJCC stages were significant (<0.05) for all comparisons except for stage
      IIIC vs. IV; while P values for pairwise comparisons among different 7th AJCC
      stages were significant (<0.05) for all comparisons except for stage IIIA vs.
      IIIB and stage IIIC vs. IV. Among clinically-staged patients and according to
      either the clinical 8th AJCC or the 7th AJCC, significant overlap in outcomes
      existed between different stages. Among pathologically-staged patients, c
      statistic for the pathological 8th system was: 0.762; while for the 7th system,
      it was: 0.763. Among clinically-staged patients, c-statistic for the clinical 8th
      system was: 0.634; while for the 7th system, it was: 0.637. CONCLUSION: Compared
      to the 7th system, the 8th system does not bring about significant prognostic
      improvement (for either clinically- or pathologically-staged patients).

PMID- 29198150
TI  - The effect of tumor-derived exosomes on immune regulation and cancer
      immunotherapy.
AB  - Tumor-derived exosomes (TEX) carry both immunosuppressive and immunostimulatory
      receptor/ligands that in part mimic the profiles of the parent tumor cells.
      Operating as an intercellular communication system, TEX deliver protumor or
      antitumor signals to immune and nonimmune cells reprogramming their functions.
      Mechanisms responsible for cellular reprogramming include cell surface signaling
      and/or uptake of TEX by recipient cells. Once internalized, TEX transfer mRNA,
      miRNA and proteins that promote transcriptional/translational activities. TEX
      mediated signaling is contextual and, in the tumor microenvironment, TEX largely
      mediate suppression. TEX may interfere with immune therapies either by
      sequestration of therapeutic antibodies or elimination of vaccine-induced or
      adoptively-transferred immune effector cells. TEX are emerging as an ubiquitous
      subcellular system regulating immune responses in patients with cancer.

PMID- 29198152
TI  - Development of sustained release gastro-retentive tablet formulation of
      nicardipine hydrochloride using quality by design (QbD) approach.
AB  - The objective of the present study was to develop a sustained release gastro
      retentive (SRGR) tablet formulation of nicardipine hydrochloride (HCl) for once-a
      day dosing using the quality by design (QbD) approach. The quality target product
      profile of nicardipine HCl SRGR tablet formulation was defined, and critical
      quality attributes (CQAs) were identified. Potential risk factors were identified
      using a fish bone diagram and failure mode effect analysis (FMEA) tool and
      screened by the Plackett-Burman design, and finally nicardipine HCl SRGR tablet
      formulation was optimized using the Box-Behnken design. The tablets were prepared
      by a direct compression technique using polymers such as
      hydroxypropylmethylcellulose (HPMC K15M), glyceryl behenate, alone or in
      combinations and other standard excipients. Sodium bicarbonate was incorporated
      as a gas-generating agent. The effects of polymers and sodium bicarbonate on the
      drug release profile and floating properties were investigated as these
      parameters are likely to affect the desired once-a-day dosing regimen and finally
      the therapeutic efficacy of SRGR drug delivery systems. It was observed that
      formulation variables X1: Glyceryl behenate (mg/tab) and X2: HPMC K15M (mg/tab)
      strikingly influenced the drug release (%) (Y1), whereas floating lag time (min)
      (Y2) was significantly impacted by the formulation variable X3: Sodium
      bicarbonate (mg/tab). A design space plot within which the CQAs remained
      unchanged was established at a lab scale. In conclusion, this study demonstrated
      the suitability of a glyceryl behenate-HPMC K15M polymer combination along with
      sodium bicarbonate to achieve SRGR tablet formulation for once-a-day dosing of
      nicardipine HCl using the systematic QbD approach.

PMID- 29198153
TI  - How do men's magazines talk about penises?
AB  - Constructions of masculinity have shifted and changed but the central role of the
      penis has remained firm. Yet, despite the implications for sexual health, there
      has been very little research on discourses around penises. The messages men
      receive about their manhood is apparent in articles in men's magazines. We
      conducted a discursive analysis of the ways in which penises were discussed in
      four market leading UK titles: Loaded, Men's Health, GQ and Attitude. Two broad
      discourses were identified, termed Laddish and Medicalised, both of which create
      fear-ridden spaces where men are bombarded with unachievable masculine ideals and
      traumatic examples of mutilated members. We discuss how health psychologists
      could use the findings to communicate with men about their sexual health needs
      using this channel.

PMID- 29198155
TI  - Delayed second twin delivery: benefits and risks.
AB  - BACKGROUND: An increasing number of reports describe the delayed second twin
      delivery for days, or weeks with good results in the majority of the cases, and
      different survival rate between centers, without reported randomized controlled
      trials (RCTs). OBJECTIVES: This study was designed to evaluate the suggested
      management of the delayed second twin delivery in the Sabah Maternity Hospital
      regarding its outcome, possible risks, and benefits. PATIENTS AND METHODS: Forty
      seven twin pregnancies with preterm labor (PTL) of the first fetus between 20-30
      weeks, and delayed delivery of the second twin were included in this study.
      Studied women signed informed consent about the possible risks of keeping the
      live fetus in the hostile intrauterine environment, and benefits of the prolonged
      gestation for the second twin. Throughout the conservative treatment of the
      second twin, the studied women were hospitalized with regular follow up for
      infections, consumptive coagulopathy parameters, and wellbeing of the second
      twin. RESULTS: There was significant difference in the gestational age at
      delivery between the first and second twin (22.6 +/- 3.4 versus 34.3 +/- 2.5
      weeks; respectively, p = .01). There was significant difference in the birth
      weight between the first and second twin (435 +/- 91.2 versus 1472 +/- 61.5 g;
      respectively, p = .004). The rate of the cesarean delivery was significantly high
      during delivery of the second twin compared with the first twin (23.4% (11/47)
      versus 0% (0/47); respectively, p = .0001) with high survival rate for the second
      twin (85.1% (40/47)) after the delayed second twin delivery. CONCLUSIONS: The
      birth weight, the gestational age, and the survival rate of the studied second
      twin significantly increased after the suggested management of the delayed second
      twin delivery.

PMID- 29198154
TI  - Population trends in mitral valve surgery in Finland between 1997 and 2014: the
      finnish CVD register.
AB  - OBJECTIVES: Contemporary, nationwide data on trends in mitral valve surgery are
      scarce. Our aim was to investigate changes in procedure rates, patient selection,
      and post-procedural prognosis of open-heart mitral valve surgery in Finland.
      DESIGN: We combined data from three nationwide administrative registers with
      compulsory reporting. We identified patients who had undergone first-ever open
      heart mitral valve surgery between 1997 and 2014 and followed them for adverse
      events. We examined trends in mitral valve surgery over three six-year time
      periods (1997-2002, 2003-2008, and 2009-2014). RESULTS: 3684 mitral valve
      procedures (mean age: 67.0 +/- 10.9 years, 42.6% women) were performed in 1997
      2014 in Finland. During this period, mitral valve repair operations became more
      common than replacements and we observed an increasing trend in the use of
      bioprosthetic valves. Between 1997-2002 and 2009-2014, the mean age of patients
      undergoing mitral valve surgery and the proportion of urgent surgeries increased
      (p < .001 for both). The proportion of women undergoing surgery decreased while
      the share of patients with hypertension (p = .023) or diabetes (p = .026)
      increased. The multivariable-adjusted risk of 28-day (hazard ratio, 0.55; 95%
      confidence interval, 0.37-0.83) and 6-year (hazard ratio, 0.80; 95% confidence
      interval, 0.67-0.97) post-operative mortality was lower in the last six-year
      period than in 1994-1998. CONCLUSIONS: Short- and long-term mortality of mitral
      valve surgery patients in Finland has decreased from 1997 to 2014 despite the
      patients being older and having more comorbidities. Understanding the changing
      characteristics and prognosis of these patients is important for the
      interpretation of previous and future cohort studies and trials.

PMID- 29198156
TI  - Mixed Ovarian Tumor Composed of Brenner Tumor and Adult-Type Granulosa Cell
      Tumor: A Case Report of a Very Rare Mixed Ovarian Tumor and a Review of the
      Literature.
AB  - A combination of ovarian tumors with the same histogenetic origin but different
      histologic subtype is relatively common, whereas a co-occurrence of tumors with
      different histogenetic origin is rare. We report a case of mixed ovarian tumor
      composed of Brenner tumor and adult-type granulosa cell tumor, a combination that
      to the best of our knowledge has not been reported in the literature until now.

PMID- 29198157
TI  - Efficacy and safety evaluation of Cimicifuga foetida extract in menopausal women.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of long
      term treatment with Cimicifuga foetida extract in menopausal women. METHODS: A
      prospective, randomized, controlled clinical trial was conducted. A total of 96
      early postmenopausal women were randomly assigned to three groups: group A
      received 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate on
      days 19-30; group B received 1 mg estradiol valerate daily plus 100 mg micronized
      progesterone on days 19-30; group C received 100 mg C. foetida extract daily. The
      efficacy was evaluated. Safety parameters were recorded. RESULTS: A total of 81
      patients completed the treatment and follow-up visit. The modified Kupperman
      Menopausal Index scores decreased after 3 months in all groups. No significant
      changes were observed in the liver, renal function and components of metabolic
      syndrome in group C (p > 0.05). There were no significant differences in the
      incidences of metabolic syndrome among the three groups (p > 0.05). After 24
      months, the endometrial thickness increased significantly in group B (p = 0.014),
      but not in the C. foetida extract group (p > 0.05). CONCLUSIONS: C. foetida
      extract is safe and effective for the treatment of menopausal symptoms in
      postmenopausal women.

PMID- 29198158
TI  - Ureteritis Cystica Presenting as a Single Polypoid Mass.

PMID- 29198159
TI  - Cystic Hypersecretory Hyperplasia of Breast.

PMID- 29198160
TI  - Targeting oncoproteins for degradation by small molecules in myeloid leukemia.
AB  - Oncoproteins play a vital role in the pathogenesis of myeloid leukemia. Most
      targeted therapies for myeloid leukemia are small molecules or monoclonal
      antibodies that inhibit the activity of the oncoproteins. However, leukemia cells
      often develop resistance to these drugs through overexpression of the target
      protein and/or by obtaining new mutations in the target protein to render them
      resistant to the drug. Oncoproteins degradation induced by small molecules
      through ubiquitin or autophagy pathway is considered a better way to avoid drug
      resistance. Here, we describe the latest advances in the use of small molecules
      to degrade oncoproteins. We first discuss examples of existing cancer drugs and
      candidate drugs that act by degrading oncoproteins, and then review the latest
      development of rational design of small molecules that induce selective
      degradation of target proteins. Furthermore, small-molecule-based proteolysis
      targeting chimeras (PROTACs) have demonstrated that this technology can
      effectively degrade target proteins.

PMID- 29198161
TI  - Teaching to varied disciplines and educational levels simultaneously: An
      innovative approach in a neonatal follow-up clinic.
AB  - PURPOSE: Across various health conditions and geographic regions, there remains a
      dearth of clinicians with the expertise and confidence to identify and manage
      children with disabilities. At the front line of this crisis are clinician
      educators, who are tasked with caring for these unique patients and with training
      the future workforce. Balancing patient care and clinical instruction
      responsibilities is particularly challenging when trainees of varied educational
      levels and specialties report simultaneously. The lack of a standard curriculum
      further compounds the clinician-educator's teaching demands and threatens the
      consistency of trainees' learning. Recognizing these challenges in their work in
      a neonatal follow-up clinic, the authors sought a solution through an established
      curriculum development process. MATERIALS AND METHODS: A needs assessment survey
      was conducted to gauge medical trainees' knowledge, skills, and experiences.
      Applying needs assessment findings, the authors developed a curriculum, which was
      administered online to several trainee cohorts just prior to rotations in the
      neonatal follow-up clinic. RESULTS: After completing the curriculum, trainees
      scored significantly higher on neonatal follow-up knowledge tests. CONCLUSIONS:
      Providing advance exposure helped to ensure that trainees arrived with comparable
      basal knowledge, which served as a foundation for more advanced instruction. This
      curricular approach may be useful across teaching venues, especially those with
      multi-level or multi-discipline learners.

PMID- 29198162
TI  - Neurobrucellosis presenting as clinically definite amyotrophic lateral sclerosis.
AB  - : Purpose/Aim: We describe the first case of a patient with neurobrucellosis
      presenting with clinically-definite ALS. MATERIAL AND METHODS: A 48-year old male
      patient, in whom the diagnoses of systemic brucellosis and clinically definite
      ALS were undoubtedly confirmed and were eventually causally interrelated. The
      disease-specific antibiotic therapy was unsuccessful to slow the evolution of the
      motor neuron disease and the patient became non ambulatory over time. RESULTS:
      Considering the close temporal association of ALS onset with the systemic
      Brucella infection and consequent antigenic stimuli, we might suggest that human
      brucellosis might have triggered a process of motor neuron degeneration in
      keeping with neurobrucellosis, primarily due to parainfectious mechanism.
      CONCLUSION: Our case helps to shed light on the factors that may trigger or only
      fasten motor neuron disease manifestations.

PMID- 29198163
TI  - Association between ABCB1 polymorphisms and response to first-generation
      antiepileptic drugs in a Tunisian epileptic population.
AB  - PURPOSE: We aimed in this study to investigate the association between the ATP
      Binding Cassette sub-family B, member1 (ABCB1) polymorphisms: C1236T (rs1128503),
      G2677T (rs2032582) and C3435T (rs1045642), and the resistance to antiepileptic
      drugs (AEDs). MATERIALS AND METHODS: The Polymerase Chain Reaction-Restriction
      Fragment Length Polymorphism genotyping of ABCB1 polymorphisms was conducted on
      153 Tunisian epileptic patients treated with AEDs. RESULTS: Two genetic
      polymorphisms of the ABCB1 gene seemed to influence the response to AEDs. In
      fact, the G2677T T and the C3435T T alleles appeared to increase the risk of
      developing AEDs resistance (ORs* = 3.13; 95%CI = [1.16-8.98]; p = 0.024 and ORs*
      = 3.10; 95%CI = [1.15-8.37]; p = 0.025), respectively. However, the C1236T T
      allele did not seemed to influence the response to AEDs (ORs* = 1.14; 95%CI =
      [0.53-3.88]; p = 0.471). Haplotypic analysis indicated high-degree linkage
      disequilibrium of ABCB1 polymorphisms. Our results showed a synergic effect, in
      fact patients with the CTT and TTT haplotypes were more likely to be drug
      resistant than patients with the CGC haplotype, these associations remained
      significant even after adjustment for confounding parameters (ORs* = 2.68; 95%CI
      = [1.11-8.25]; p = 0.033 and ORs* = 3.76; 95%CI = [1.69-21.05]; p = 0.006,
      respectively). CONCLUSION: The G2677T T and C3435T T alleles as well as the TT,
      CTT and TTT haplotypes seemed to be significantly associated with drug-resistance
      epilepsy in our population. Genetic predisposition, involved in this resistance,
      may contribute to the establishment of a personal optimized therapy for newly
      diagnosed epileptic patients.

PMID- 29198164
TI  - Stability and Hopf bifurcation for a five-dimensional virus infection model with
      Beddington-DeAngelis incidence and three delays.
AB  - In this paper, the dynamical behaviours for a five-dimensional virus infection
      model with three delays which describes the interactions of antibody, cytotoxic T
      lymphocyte (CTL) immune responses and Beddington-DeAngelis incidence are
      investigated. The reproduction numbers for virus infection, antibody immune
      response, CTL immune response, CTL immune competition and antibody immune
      competition, respectively, are calculated. By using the Lyapunov functionals and
      linearization method, the threshold conditions on the local and global stability
      of the equilibria for infection-free, immune-free, antibody response, CTL
      response and interior, respectively, are established. The existence of Hopf
      bifurcation with immune delay as a bifurcation parameter is investigated by using
      the bifurcation theory. Numerical simulations are presented to justify the
      analytical results.

PMID- 29198165
TI  - Undecaprenyl phosphate metabolism in Gram-negative and Gram-positive bacteria.
AB  - Undecaprenyl phosphate (UP) is essential for the biosynthesis of bacterial
      extracellular polysaccharides. UP is produced by the dephosphorylation of
      undecaprenyl diphosphate (UPP) via de novo synthetic and recycling pathways. Gram
      positive bacteria contain remarkable amounts of undecaprenol (UOH), which is
      phosphorylated to UP, although UOH has not been found in Gram-negative bacteria.
      Here, current knowledge about UPP phosphatase and UOH kinase is reviewed.
      Dephosphorylation of UPP is catalyzed by a BacA homologue and a type-2
      phosphatidic acid phosphatase (PAP2) homologue. The presence of one of these UPP
      phosphatases is essential for bacterial growth. The catalytic center of both
      types of enzyme is located outside the cytoplasmic membrane. In Gram-positive
      bacteria, an enzyme homologous to DgkA, which is the diacylglycerol kinase of
      Escherichia coli, catalyzes UOH phosphorylation. The possible role of UOH and the
      significance of systematic construction of Staphylococcus aureus mutants to
      determine UP metabolism are discussed.

PMID- 29198166
TI  - Improvement of the activity and thermostability of microbial transglutaminase by
      multiple-site mutagenesis.
AB  - Microbial transglutaminase (MTG) is an enzyme widely used in the food industry.
      Mutiple-site mutagenesis of Streptomyces mobaraensis transglutaminase was
      performed in Escherichia coli. According to enzymatic assay and thermostability
      study, among three penta-site MTG mutants (DM01-03), DM01 exhibited the highest
      enzymatic activity of 55.7 +/- 1.4 U/mg and longest half-life at 50  degrees C
      (418.2 min) and 60  degrees C (24.8 min).

PMID- 29198167
TI  - Global dynamics of an epidemiological model with age of infection and disease
      relapse.
AB  - In this paper, an epidemiological model with age of infection and disease relapse
      is investigated. The basic reproduction number for the model is identified, and
      it is shown to be a sharp threshold to completely determine the global dynamics
      of the model. By analysing the corresponding characteristic equations, the local
      stability of a disease-free steady state and an endemic steady state of the model
      is established. By means of suitable Lyapunov functionals and LaSalle's
      invariance principle, it is verified that if the basic reproduction number is
      less than unity, the disease-free steady state is globally asymptotically stable,
      and hence the disease dies out; if the basic reproduction number is greater than
      unity, the endemic steady state is globally asymptotically stable and the disease
      becomes endemic.

PMID- 29198168
TI  - Simultaneous laparoscopic proctocolectomy (TaTME) and robot-assisted radical
      prostatectomy for synchronous rectal and prostate cancer.
AB  - OBJECTIVE: We would like to present a patient with a history of ulcerative
      colitis suffering from a synchronous rectal and prostate cancer treated with a
      laparoscopic total proctocolectomy (with TaTME) and Retzius sparing RARP
      simultaneously. METHODS: Retzius sparing RARP with bilateral lymph node
      harvesting was performed first. Afterwards, TaTME was commenced with the
      placement of a Lonestar(r) retractor and GelPort(r). Anterior dissection was
      troubled unexpectedly by outspoken fibrosis. For that reason, it was completed
      laparoscopically. We then continued with the laparoscopic total proctocolectomy.
      Last, a transanal circular stapled ileoanal anastomosis was created and a
      derivating ileostomy was installed. RESULTS: Postoperative proctoscopy showed a
      patent ileoanal anastomosis. After removal of the Foley catheter on day 21, the
      patient was immediately continent. Prostate specimen revealed a pT2cN1M0
      transmural invasive adenocarcinoma with a Gleason score of 7 (3 + 4). Pathology
      analysis of the rectum revealed a stage IIIc transmural invasive moderately
      differentiated rectal adenocarcinoma (pT3N2bM0) with free margins. He was
      referred for adjuvant chemotherapy. CONCLUSIONS: In this case, the combination of
      TaTME and Retzius sparing RARP for synchronous rectal and prostate cancer was
      feasible and safe. We suggest performing the anterior TaTME dissection last, due
      to disturbing blood flow into the operating field after prostatectomy.

PMID- 29198170
TI  - The effects of aging on hepatic microsomal scaling factor and hepatocellularity
      number in the horse.
AB  - 1. Scaling factor values for the in vitro-in vivo extrapolation of hepatic
      metabolic clearance for xenobiotics have not yet been determined in horses.
      Scaling factors were determined by comparing the total protein and or cytochrome
      (CYP) P450 content in microsomes and cryopreserved hepatocytes against the
      content in the liver. 2. Microsomal protein per gram of liver (MPPGL) and
      hepatocellularity number per gram of liver (HPGL) using CYP P450 content method
      ranged 41-73 mg/gram of liver (mean= 57 mg/gram of liver, n = 39) and 146-320 *
      106 cells/g of liver (mean = 227* 106 cells/g of liver, n = 18), respectively and
      156-352 * 106 cells/g of liver (mean = 232* 106 cells/g of liver) using total
      protein method. 3. A non-monotonic and inverse relationship between age and MPPGL
      and HPGL, respectively, was observed. Between one and 20 y of age, the liver cell
      size decreases as age increases. Subsequently, the cell size increases until the
      hepatocytes of the oldest horses approached the size found in the youngest
      horses. Hepatocyte density was inversely related to the size of the hepatocytes.
      4. This study provides the first extensive and comprehensive data demonstrating
      the relationship between the size of hepatocytes and HPGL in any species.

PMID- 29198169
TI  - Stress-response transcription factors Msn2 and Msn4 couple TORC2-Ypk1 signaling
      and mitochondrial respiration to ATG8 gene expression and autophagy.
AB  - Macroautophagy/autophagy is a starvation and stress-induced catabolic process
      critical for cellular homeostasis and adaptation. Several Atg proteins are
      involved in the formation of the autophagosome and subsequent degradation of
      cytoplasmic components, a process termed autophagy flux. Additionally, the
      expression of several Atg proteins, in particular Atg8, is modulated
      transcriptionally, yet the regulatory mechanisms involved remain poorly
      understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin
      insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the
      heterodimeric Zinc-finger transcription factors Msn2 and Msn4. We find that Msn2
      and Msn4 promote ATG8 expression downstream of the histone deacetylase complex
      (HDAC) subunit Ume6, a previously identified negative regulator of ATG8
      expression. Moreover, we demonstrate that TORC2-Ypk1 signaling is functionally
      linked to distinct mitochondrial respiratory complexes. Surprisingly, we find
      that autophagy flux during amino acid starvation is also dependent upon Msn2-Msn4
      activity, revealing a broad role for these transcription factors in the autophagy
      response.

PMID- 29198171
TI  - Caring for Care Workers.
AB  - Carework-the paid and unpaid work in healthcare, education, childcare, mental
      health, elder care, families, and social services-is linked by the social and
      ethical obligation to care for vulnerable populations and is a major economic
      sector and important source of employment internationally. This special issue of
      New Solutions focuses on understanding working conditions and workplace health
      and safety in carework professions and for seeking solutions to these dilemmas.
      As members of the Carework Network Steering Committee, we reflect on the
      importance of the topics raised in this special issue and describe next steps for
      carework research and scholarship.

PMID- 29198172
TI  - Ethanol effect on acid resistance of selected enteric polymers.
AB  - The aim of this study was to investigate under in vitro conditions the influence
      of ethanol on acid resistance of four commercially-available enteric polymers
      (Acryl-EZE(r), AQOAT(r), Hypromellose phthalate, and Sureteric(r)). For this
      purpose, custom-prepared paracetamol tablets were coated with the enteric
      polymers and tested for release using the buffer-addition method. Ten different
      hydro-ethanolic media were used in the acid stage corresponding to five levels of
      ethanol (0, 5, 10, 20, and 40% v/v) in two acidic solutions representing low and
      high gastric pH (0.1 N HCl pH 1.2, LGpH, and phosphate buffer pH 4.0, HGpH,
      respectively). The coats were found to resist both types of acidic solution with
      ethanol percentages up to 10% leading to release profiles that conformed with the
      pharmacopeial requirements (<10% release after 2 h in acid stage) except for
      Acryl-EZE(r), which showed a premature release in HGpH media. At the higher
      ethanol levels (20 and 40%), premature release associated with increased acid
      uptake by coated tablets was noticed for all polymers and more remarkably in HGpH
      media. ANOVA tests revealed significant effects of polymer type, acidic solution
      type, and ethanol level on the onset and extent of premature release.

PMID- 29198174
TI  - Intracranial complications of midline nasal dermoid cysts.
AB  - BACKGROUND: Nasal dermoid cysts are common tumors in children. Due to anomalies
      in embryologic development of the nasal complex, sometimes an intracranial
      extension exists. When these cysts become infected they can lead to meningitis,
      brain abscess and death. METHODS: We report the case of a 1.5-year-old girl
      admitted to the paediatric intensive care unit after infection of a nasal dermoid
      cyst. RESULTS: The infant had a spiking fever and epileptic seizures. She was
      stabilized, intubated and a CT scan showed a subcutaneous mass with an adjacent
      zone of encephalitis and brain abscess formation. Neurosurgical interventions
      were necessary to lower intracranial pressure and control infectious spread.
      After a hospital stay of 69 days the child could be discharged. Due to her young
      age, irreversible brain damage is expected. CONCLUSION: Nasal midline dermoid
      cysts are considered benign swellings. When an intracranial extension exists,
      infection can lead to deleterious complications. It is important for health care
      practitioners to be aware of this imminent risk. Suspicion of a nasal midline
      dermoid cyst should prompt a careful clinical work-up with an ultrasound followed
      by CT or MRI imaging. The treatment is complete excision to avoid disastrous
      complications and recurrences.

PMID- 29198175
TI  - New semicarbazones as gorge-spanning ligands of acetylcholinesterase and
      potential new drugs against Alzheimer's disease: Synthesis, molecular modeling,
      NMR, and biological evaluation.
AB  - Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)
      ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4
      dhihydroacridin-1(2H)-ylidene)hydrazinecarboxamide (4) were synthesized and
      evaluated for their anticholinesterase activities. In vitro tests performed by
      NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition
      of acetylcholinesterase (AChE). This result was corroborated through further
      docking and molecular dynamics studies, suggesting that the new compounds can
      work as gorge-spanning ligands by interacting with two different binding sites
      inside AChE. Also, in silico toxicity evaluation suggested that these new
      compounds can be less toxic than tacrine.

PMID- 29198176
TI  - Abstracts presented at the 22nd Annual Congress of the Belgian Society of
      Internal Medicine, 15-16 December 2017, Dolce La Hulpe, La Hulpe, Belgium.

PMID- 29198173
TI  - Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via
      extracellular vesicles with a hybrid autophagosome-exosome-like phenotype.
AB  - The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the
      cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies,
      including Parkinson disease and dementia with Lewy bodies (DLB). Emerging
      evidence suggests that ALP influences SNCA release, but the underlying cellular
      mechanisms are not well understood. Several studies identified SNCA in
      exosome/extracellular vesicle (EV) fractions. EVs are generated in the
      multivesicular body compartment and either released upon its fusion with the
      plasma membrane, or cleared via the ALP. We therefore hypothesized that
      inhibiting ALP clearance 1) enhances SNCA release via EVs by increasing
      extracellular shuttling of multivesicular body contents, 2) alters EV biochemical
      profile, and 3) promotes SNCA cell-to-cell transfer. Indeed, ALP inhibition
      increased the ratio of extra- to intracellular SNCA and upregulated SNCA
      association with EVs in neuronal cells. Ultrastructural analysis revealed a
      widespread, fused multivesicular body-autophagosome compartment. Biochemical
      characterization revealed the presence of autophagosome-related proteins, such as
      LC3-II and SQSTM1. This distinct "autophagosome-exosome-like" profile was also
      identified in human cerebrospinal fluid (CSF) EVs. After a single intracortical
      injection of SNCA-containing EVs derived from CSF into mice, human SNCA
      colocalized with endosome and neuronal markers. Prominent SNCA immunoreactivity
      and a higher number of neuronal SNCA inclusions were observed after DLB patient
      CSF EV injections. In summary, this study provides compelling evidence that a)
      ALP inhibition increases SNCA in neuronal EVs, b) distinct ALP components are
      present in EVs, and c) CSF EVs transfer SNCA from cell to cell in vivo. Thus,
      macroautophagy/autophagy may regulate EV protein composition and consequently
      progression in synucleinopathies.

PMID- 29198177
TI  - Clinicopathologic features of solid pseudopapillary pancreatic neoplasms in an
      Eastern Caribbean population.
AB  - Pancreatic solid pseudopapillary neoplasms (SPNs) are uncommon lesions across the
      globe. Their incidence is unknown in the Caribbean. This retrospective study
      sought to document the clinicopathologic features of pancreatic SPNs in an
      Eastern Caribbean population. We examined data from the hospital records of all
      patients with SPN in Trinidad and Tobago, finding 11 cases over five years,
      equating to an incidence of 0.17 cases per 100,000 population per year. The
      lesions occurred in girls and young women at a mean age of 25 years, with a
      propensity for those of Afro-Caribbean descent. Poor prognostic factors
      (histologic invasion of the capsule, lymphovascular invasion, spindle cells,
      anaplastic cells and/or excessive mitotic figures) were present in 82% at the
      time of diagnosis. These tumours are uncommon in our population, and since most
      have poor prognostic features at diagnosis, we advocate an aggressive surgical
      approach.

PMID- 29198178
TI  - Zero tolerance for acronyms.

PMID- 29198179
TI  - Screening for Chlamydia trachomatis and Neisseria gonorrhoeae infection among
      asymptomatic men who have sex with men in Bangkok, Thailand.
AB  - We report positivity rates of Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) infection at each anatomic site among asymptomatic men who have
      sex with men (MSM). We calculated the number needed to screen (NNS) to detect CT
      and NG infection at each anatomic site. From 2006 to 2010, we enrolled Thai MSM,
      age >= 18 years into the Bangkok MSM Cohort Study. Participants underwent
      physical examination and had rectal, urethral, and pharyngeal screening for CT
      and NG infection using nucleic acid amplification tests (NAATs). Of 1744
      enrollees, 1696 (97.2%) had no symptoms of CT and NG infection. The positivity
      rates of CT and NG infection at any site were 14.3% (rectum, urethra, pharynx)
      and 6.4% (rectum, urethra), respectively. The NNS to detect rectal CT and rectal
      NG infections was 10 and 16, respectively (p < 0.05). For urethral infection, the
      NNS of CT was lower than the NNS of NG (22, 121: p < 0.05). The lowest NNS found
      for rectal CT infection was in HIV-infected MSM (6, 5-8). Asymptomatic CT and NG
      infection were common among MSM in Bangkok, Thailand and frequently detected in
      the rectum. In setting where screening in all specimens using NAAT is not
      feasible, rectal screening should be a priority.

PMID- 29198180
TI  - Converging epidemics of sexually transmitted infections and bacterial vaginosis
      in southern African female adolescents at risk of HIV.
AB  - Adolescents in Africa are at high risk for HIV infection, other sexually
      transmitted infections (STIs) and bacterial vaginosis (BV). Since behavior and
      burden of STIs/BV may influence HIV risk, behavioral risk factors and prevalence
      of STIs/BV were compared in HIV-seronegative adolescent females (n = 298; 16-22
      years) from two South African communities (Soweto and Cape Town). STIs (
      Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma
      genitalium, herpes simplex virus (HSV)-1, HSV-2, Treponema pallidum, and
      Haemophilus ducreyi) were detected by multiplex polymerase chain reaction, human
      papillomavirus (HPV) by Roche Linear Array, and BV by Nugent scoring. Rates of BV
      (Nugent >=7; 46.6%) and HPV (66.8%) were high in both communities. Prevalence of
      C. trachomatis and N. gonorrhoeae were >2-fold higher in Cape Town than Soweto
      (Chlamydia: 42% [62/149] versus 18% [26/148], p < 0.0001; gonorrhoea 11% [17/149]
      versus 5% [7/148], p = 0.05). Only 24% of adolescents with vaginal discharge
      causing STIs or BV were symptomatic. In South African adolescents, clinical
      symptoms compatible with vaginal discharge syndrome had a sensitivity of 23% and
      specificity of 85% for the diagnosis of discharge-causing STI or BV. In a region
      with high HIV prevalence and incidence, >70% of young women with treatable
      conditions that could enhance HIV risk would have been missed because they lacked
      symptoms associated with syndromic management.

PMID- 29198181
TI  - 2017 European guideline for the management of pelvic inflammatory disease.
AB  - The European guideline for the management of pelvic inflammatory disease includes
      evidence-based advice on the investigation and treatment of pelvic inflammatory
      disease (PID). It has been updated to acknowledge the role of Mycoplasma
      genitalium as an important cause of PID with testing now recommended for women
      presenting with possible PID and for the male partners of women with confirmed M.
      genitalium infection. Recent evidence suggests that serious adverse events are
      uncommon when using moxifloxacin and its use is now recommended as a first-line
      therapy, especially in those women with M. genitalium PID. The potential utility
      of MRI scanning of the pelvis in excluding differential diagnoses has been
      highlighted. The use of doxycycline is now suggested as empirical treatment for
      male partners of women with PID to reduce exposure to macrolide antibiotics,
      which has been associated with increased resistance in M. genitalium.

PMID- 29198182
TI  - Improving the coverage of prevention of mother-to-child transmission of HIV
      services in Nigeria: should traditional birth attendants be engaged?
AB  - Traditional birth attendants (TBAs) play an important role in the provision of
      care to pregnant women in rural parts of Nigeria, but they are barely engaged by
      the formal healthcare system in expanding the low coverage of prevention of
      mother-to-child transmission of HIV (PMTCT) services. Using a systematic
      approach, we engaged TBAs in Abia and Taraba States to scale-up PMTCT services
      under the National Agency for Control of AIDS Comprehensive AIDS Program with
      States. We conducted mapping of the TBAs, built their capacities, obtained their
      buy-in on mobilization of their clients and other pregnant women for HIV testing
      service outreaches, and established referral and linkage systems. A total of 720
      TBAs were mapped (Abia 407; Taraba 313). Three hundred and ninety-nine TBAs who
      participated in the capacity-building meeting were linked to 115 primary
      healthcare centers (PHCs) in Abia State, while 245 TBAs were linked to 27 PHCs in
      Taraba State. From July 2016 to March 2017, the outreaches contributed 20% to the
      overall total number of pregnant women counseled, tested and received results,
      and 12% to the total number of HIV-infected women identified. There was a
      considerable yield of HIV-infected pregnant women among those tested in the TBA
      outreaches in comparison with the supported antenatal facilities (2% versus 3%,
      respectively). Engaging TBAs has the potential to improve the coverage of PMTCT
      services in Nigeria.

PMID- 29198183
TI  - 18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging
      in HIV-infected patients with lymphadenopathy, with or without fever and/or
      splenomegaly.
AB  - We audited whether 18F-Fluorodeoxyglucose positron emission tomography-computed
      tomography (18FDG PET-CT) imaging could discriminate between different diagnoses
      in HIV-infected patients presenting with lymphadenopathy, with or without fever
      and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in
      lymphoma and mycobacterial and fungal infections and were lower but similar in
      those with human herpesvirus (HHV) 8-associated disease and HIV-associated
      reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax >=10, excluded
      diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV
      associated reactive lymphadenopathy was additionally excluded in those who had
      undetectable plasma HIV viral loads. This audit suggests 18FDG PET-CT imaging did
      not permit discrimination between specific diagnoses but has utility in
      identifying lymph nodes with increased avidity that could be targeted for biopsy
      and in ruling out significant pathology.

PMID- 29198184
TI  - Impact of maternal iron deficiency on the auditory functions in the young and
      adult guinea pig.
AB  - OBJECTIVES: The aim of this study was to evaluate the hearing function in the
      guinea pig offspring at post-natal day (PNd) 24 and PNd84 born from dams
      suffering from iron deficiency during pregnancy and lactation by using the
      auditory brainstem response (ABR). METHOD: Female guinea pigs (n = 24 per dietary
      group) were fed an iron sufficient (IS) diet (114 mg/kg) or an iron deficient
      (ID) diet (11.7 mg/kg) during the gestation and lactation periods. Pups in both
      groups were weaned at PNd9 and given the IS diet. The hematocrit level was
      measured at every trimester of pregnancy and at the day of sacrifice in dams and
      at PNd24 and PNd84 in pups. The animal body weight was measured on every second
      day until the day of sacrifice. The ABR was used in pups to measure the hearing
      threshold using a broad range of stimulus intensities and latency at 100 and 80
      dB in response to 2, 4, 8, 16, and 32 kHz tone pips at PNd24 and 84. RESULTS AND
      DISCUSSION: No significant difference between dietary groups was measured in
      hearing threshold and absolute latencies in pups at PNd24 and PNd84. Although the
      ID offspring (n = 16) did not differ in brainstem transmission times (BTTs) at 80
      dB compare to the IS siblings (n = 25) at PNd24, they showed significant delayed
      inter-peak latency (IPL) I-IV at 100 dB suggesting a delayed BTT. At PNd84, the
      latency of all peaks including IPL I-IV at 80 and 100 dB significantly decreased
      and was also similar in pups from both dietary groups suggesting a better brain
      maturation. This is the first study investigating the long-term impact of
      maternal iron deficiency on the auditory functions in the guinea pig offspring
      during early development to adulthood.

PMID- 29198185
TI  - Role of substance use in HIV care cascade outcomes among people who inject drugs
      in Russia.
AB  - BACKGROUND: Engaging people who drink alcohol or inject drugs in HIV care can be
      challenging, particularly in Eastern Europe. Healthcare facilities in Russia are
      organized by specialty; therefore linking patients from addiction care to HIV
      hospitals has been difficult. The HIV care cascade outlines stages of HIV care
      (e.g., linkage to care, prescribed antiretroviral therapy [ART], and achieving
      HIV viral suppression). We hypothesized that unhealthy alcohol use, injection
      drug use, and opioid craving are associated with unfavorable HIV care cascade
      outcomes. METHODS: We analyzed data from a cohort (n = 249) of HIV-positive
      Russians who have been in addiction hospital treatment in the past year and had a
      lifetime history of injection drug use (IDU). We evaluated the association
      between unhealthy alcohol use (AUDIT score > 7 [both hazardous drinking and
      dependence]), past-month injection drug use (IDU), and opioid craving (visual
      analogue scale from 1 to 100) with HIV care cascade outcomes. The primary outcome
      was linkage to HIV care within 12 months. Other outcomes were prescription of ART
      (secondary) and achievement of undetectable HIV viral load (HVL < 500 copies/mL)
      within 12 months (exploratory); the latter was analyzed on a subset in which HVL
      was measured (n = 48). We assessed outcomes via medical record review (linkage,
      ART) and serum tests (HVL). To examine the primary outcome, we used multiple
      logistic regression models controlling for potential confounders. RESULTS: Among
      249 study participants, unhealthy alcohol use (n = 148 [59%]) and past-month IDU
      (n = 130 [52%]) were common. The mean opioid craving score was 49 (SD: 38). We
      were unable to detect significant associations between the independent variables
      (i.e., unhealthy alcohol use, IDU and opioid craving) and any HIV care cascade
      outcomes in unadjusted and adjusted analyses. CONCLUSION: In this cohort of HIV
      positive Russians with a history of IDU, individual substance use factors were
      not significantly associated with achieving HIV care cascade milestones (i.e.,
      linkage to HIV care; prescription for ART; or suppressed viral load). Given no
      detection of an association of cascade outcomes with recent unhealthy use of
      alcohol or injection drugs in this cohort, examining systemic factors to
      understand determinants of HIV care engagement for people with drug use would be
      important.

PMID- 29198186
TI  - Screening in Trauma for Opioid Misuse Prevention (STOMP): study protocol for the
      development of an opioid risk screening tool for victims of injury.
AB  - BACKGROUND: Opioid addiction and overdose are epidemic in the U.S. Victims of
      traumatic injury are at greater than average risk for opioid misuse and related
      complications. Potential risk screens and preventive interventions in this
      clinical population remain under-investigated. The current project seeks to
      develop and pilot the implementation of a screening tool for opioid risk at
      American College of Surgeons (ACS) Level I and Level II trauma centers. METHODS:
      The project began with an online survey, which was sent to Wisconsin trauma
      center medical directors and trauma coordinators for the purpose of gathering
      information on current substance use screening practices. Next, a focus group of
      trauma center staff was convened to discuss barriers and facilitators to
      screening, resources available and needed to support trauma patients with opioid
      use disorders, and measurable clinical observations that could indicate a
      patient's potential risk for opioid misuse. Data from the surveys and focus group
      were combined to inform the data collection instruments that are currently being
      administered to patients recruited from the University of Wisconsin Hospital
      Trauma Inpatient and Orthopedic Surgery Services. Eligible and consenting
      patients complete standardized measures of socio-demographics, substance use
      history, opioid misuse risk, mental health, medical history, and injury and pain
      severity. Follow up visits at weeks 4, 12, and 24 after hospital discharge assess
      hypothesized risk factors for opioid addiction and opioid use disorder diagnosis.
      At the completion of patient data collection, a forward stepwise regression will
      identify factors of most significant risk of the development of opioid use
      disorder after traumatic injury. This modeling will inform the development of a
      novel opioid risk screening tool, which will undergo pilot implementation at 4
      Wisconsin ACS Level I and Level II trauma centers, using an evidence-based
      implementation strategy with roots in systems engineering. DISCUSSION: Positive
      findings from the proposed work would lead to improved, standardized opioid risk
      screening practices among victims of traumatic injury. The ultimate goal of this
      and future work is to reduce the likelihood of opioid misuse, addiction, and
      related complications, such as overdose and death. Trial registration
      Clinicaltrials.gov registration number: NCT02861976. Date of registration: Feb 9,
      2016.

PMID- 29198187
TI  - Unusual presentation of prune belly syndrome: a case report.
AB  - BACKGROUND: Prune belly syndrome is a rare congenital malformation of unknown
      etiology, with the following triad of findings: abdominal muscle wall weakness,
      undescended testes, and urinary tract abnormalities. In most cases, detection of
      prune belly syndrome occurs during neonatal or infancy period. In this case
      report, we describe a 12-year-old boy from Ethiopia with the triad of findings of
      prune belly syndrome along with skeletal malformations. We are unaware of any
      previous report of prune belly syndrome in Ethiopia. CASE PRESENTATION: A 12-year
      old Amhara boy from the Northwest Gondar Amhara regional state presented to our
      referral hospital with a complaint of swelling over his left flank for the past 3
      months. Maternal pregnancy course and medical history were noncontributory, and
      he had an attended birth at a health center. He has seven siblings, none of whom
      had similar symptoms. On examination he had a distended abdomen, asymmetric with
      bulging left flank, visible horizontal line, upward umbilical slit, and absent
      rectus abdominis muscles. His abdomen was soft with a tender cystic, bimanually
      palpable mass on the left flank measuring 13 * 11 cm. Both testes were
      undescended and he also has developmental dysplasia of the hips. An abdominal
      ultrasound revealed a large cystic mass in his left kidney area with echo debris
      and a hip X-ray showed bilateral developmental dysplasia of the hip.
      Intraoperative findings were cystic left kidney, both testes were
      intraperitoneal, tortuous left renal vein, enlarged bladder reaching above
      umbilicus, and left megaureter. INTERVENTIONS: bilateral orchidectomy and left
      nephrectomy were done. He was given intravenously administered antibiotics for
      treatment of pyelonephritis and discharged home with an appointment for follow up
      and possible abdominoplasty. CONCLUSIONS: In the current report delayed
      presentation contributed to testicular atrophy and decision for orchidectomy.
      Furthermore, he will be at potential risk for sex hormone abnormality. Therefore,
      diagnosis of prune belly syndrome in resource-limited settings requires a high
      index of suspicion. We recommend further research to determine the optimal
      management and early diagnosis of prune belly syndrome in resource-limited
      settings.

PMID- 29198188
TI  - Blood lactose after dairy product intake in healthy men.
AB  - The absence of a dedicated transport for disaccharides in the intestine
      implicates that the metabolic use of dietary lactose relies on its prior
      hydrolysis at the intestinal brush border. Consequently, lactose in blood or
      urine has mostly been associated with specific cases in which the
      gastrointestinal barrier is damaged. On the other hand, lactose appears in the
      blood of lactating women and has been detected in the blood and urine of healthy
      men, indicating that the presence of lactose in the circulation of healthy
      subjects is not incompatible with normal physiology. In this cross-over study we
      have characterised the postprandial kinetics of lactose, and its major
      constituent, galactose, in the serum of fourteen healthy men who consumed a
      unique dose of 800 g milk or yogurt. Genetic testing for lactase persistence and
      microbiota profiling of the subjects were also performed. Data revealed that
      lactose does appear in serum after dairy intake, although with delayed kinetics
      compared with galactose. Median serum concentrations of approximately 0.02 mmol/l
      lactose and approximately 0.2 mmol/l galactose were observed after the ingestion
      of milk and yogurt respectively. The serum concentrations of lactose were
      inversely correlated with the concentrations of galactose, and the variability
      observed between the subjects' responses could not be explained by the presence
      of the lactase persistence allele. Finally, lactose levels have been associated
      with the abundance of the Veillonella genus in faecal microbiota. The measurement
      of systemic lactose following dietary intake could provide information about
      lactose metabolism and nutrient transport processes under normal or pathological
      conditions.

PMID- 29198189
TI  - A prospective association between dietary folate intake and type 2 diabetes risk
      among Korean adults aged 40 years or older: the Korean Multi-Rural Communities
      Cohort (MRCohort) Study.
AB  - It has not been well established whether dietary folate intake reduces the risk
      of diabetes development. We aimed to clarify the prospective association between
      dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults
      aged 40 years or older who were included in the Multi-Rural Communities Cohort.
      Dietary folate intake was estimated from all 106 food items listed on a FFQ, not
      including folate intake from supplements. Two different measurements of dietary
      folate intake were used: the baseline consumption and the average consumption
      from baseline until just before the end of follow-up. The association between
      folate intake and T2D risk was determined through a modified Poisson regression
      model with a robust error estimator controlling for potential confounders. For 29
      745 person years, 319 cases of diabetes were ascertained. In multivariable
      analyses, dietary folate intake was inversely associated with risk of T2D for
      women, not for men. For women, the incidence rate ratio of diabetes in the third
      tertile compared with the first tertile was 0.57 (95 % CI 0.38-0.87, P for
      trend=0.0085) in the baseline consumption model and 0.64 (95 % CI 0.43-0.95, P
      for trend=0.0244) in the average consumption model. These inverse associations
      was found in both normal fasting blood glucose group and impaired fasting glucose
      group among women. Among non-users of multinutrients and vitamin supplements, the
      significant inverse association remained. Thus, higher dietary intake of folate
      is prospectively associated with lower risk of diabetes for women.

PMID- 29198190
TI  - Sociodemographic factors associated with dietary supplement use in early
      pregnancy in a Swedish cohort.
AB  - Sociodemographic factors have been associated with dietary supplement use among
      pregnant women but few data exist in a Swedish population. This study aimed to
      identify factors associated with overall supplement use as well as use of folic
      acid, vitamin D and n-3 in early pregnancy. Women in the first trimester of
      pregnancy were included at registration to the antenatal care in 2013-2014 (n
      2109). Information regarding supplement use as well as sociodemographic and
      anthropometric data were obtained from questionnaires and medical records.
      Multivariable logistic regression analysis was performed to determine the
      relationship between sociodemographic variables and supplement use. A total of 78
      % of the participants reported using at least one dietary supplement in the first
      trimester. Folic acid supplement use was reported by 74 %, vitamin D supplement
      use by 43 % and n-3 supplement use by <5 %. Use of any type of supplement in
      early pregnancy was related to gestational age, parity, birthplace, education and
      employment. Folic acid supplement use was related to gestational age, parity,
      birthplace, income, education and employment. Vitamin D supplement use was
      related to gestational age, birthplace and education. In conclusion, in the first
      trimester of pregnancy, folic acid supplements were used by three in four women,
      while vitamin D supplements were used by less than half of the women. The results
      of this study show a socioeconomic disparity between supplement users and non
      users which may have a negative impact on the health of future generations.

PMID- 29198191
TI  - Diet and anthropometry at 2 years of age following an oral health promotion
      programme for Australian Aboriginal children and their carers: a randomised
      controlled trial.
AB  - There are marked disparities between indigenous and non-indigenous children's
      diets and oral health. Both diet and oral health are linked to longer-term health
      problems. We aimed to investigate whether a culturally appropriate multi-faceted
      oral health promotion intervention reduced Aboriginal children's intake of sugars
      from discretionary foods at 2 years of age. We conducted a single-blind, parallel
      arm randomised controlled trial involving women who were pregnant or had given
      birth to an Aboriginal child in the previous 6 weeks. The treatment group
      received anticipatory guidance, Motivational Interviewing, health and dental care
      for mothers during pregnancy and children at 6, 12 and 18 months. The control
      group received usual care. The key dietary outcome was the percent energy intake
      from sugars in discretionary foods (%EI), collected from up to three 24-h dietary
      recalls by trained research officers who were blind to intervention group.
      Secondary outcomes included intake of macronutrients, food groups, anthropometric
      z scores (weight, height, BMI and mid-upper arm circumference) and blood
      pressure. We enrolled 224 children to the treatment group and 230 to the control
      group. Intention-to-treat analyses showed that the %EI of sugars in discretionary
      foods was 1.6 % lower in the treatment group compared with control (95 % CI -3.4,
      0.2). This culturally appropriate intervention at four time-points from pregnancy
      to 18 months resulted in small changes to 2-year-old Aboriginal children's diets,
      which was insufficient to warrant broader implementation of the intervention.
      Further consultation with Aboriginal communities is necessary for understanding
      how to improve the diet and diet-related health outcomes of young Aboriginal
      children.

PMID- 29198192
TI  - Clustering of energy balance-related behaviours and parental education in
      European preschool children: the ToyBox study.
AB  - Energy balance-related behaviours (EBRB) are established in childhood and seem to
      persist through to adulthood. A lower parental educational level was associated
      with unhealthy behavioural patterns. The aim of the study is to identify clusters
      of EBRB and examine their association with preschool children's BMI and maternal,
      paternal and parental education. A subsample of the ToyBox study (n 5387)
      conducted in six European countries was used. Six behavioural clusters ('healthy
      diet and low activity', 'active', 'healthy lifestyle', 'high water and screen
      time; low fruits and vegetables (F&V) and physical activity (PA)', 'unhealthy
      lifestyle' and 'high F&V consumers') emerged. The healthiest group characterised
      by high water and F&V consumption and high PA z scores ('healthy lifestyle') was
      more prevalent among preschool children with at least one medium- or higher
      educated parent and showed markedly healthier trends for all the included EBRB.
      In the opposite, the 'unhealthy lifestyle' cluster (characterised by high soft
      drinks and screen time z scores, and low water, F&V and PA z scores) was more
      prevalent among children with lower parental, paternal and maternal education
      levels. OR identified that children with lower maternal, paternal and parental
      education levels were less likely to be allocated in the 'healthy lifestyle'
      cluster and more likely to be allocated in the 'unhealthy lifestyle' cluster. The
      'unhealthy lifestyle' cluster was more prevalent among children with parents in
      lower parental educational levels and children who were obese. Therefore,
      parental educational level is one of the key factors that should be considered
      when developing childhood obesity prevention interventions.

PMID- 29198193
TI  - Regulation of hepatic lipid deposition by phospholipid in large yellow croaker.
AB  - Dietary phospholipid (PL) supplementation has been shown to reduce lipid
      accumulation in the tissues of farmed fish; however, the mechanisms underlying
      this effect are largely unknown. Thus, the present study was conducted to
      evaluate the potential impacts of PL on hepatic lipid metabolism both in vivo and
      in vitro. For in vivo study, four experimental diets - low lipid and low PL diet,
      as control diet (LL-LP diet, containing 12 % lipid and 1.5 % PL), low-lipid and
      high-PL diet (containing 12 % lipid and 8 % PL), high-lipid and low-PL diet (HL
      LP diet, containing 20 % lipid and 1.5 % PL) and high-lipid and high-PL diet (HL
      HP diet, containing 20 % lipid and 8 % PL) - were randomly allocated to four
      groups of large yellow croaker (Larimichthys crocea) (three cages per group) with
      similar initial body weight (approximately 8 g). For in vitro study, primary
      hepatocytes isolated from large yellow croaker were incubated either with graded
      levels of phosphatidylcholine (PC) (0-250 MUm) or small interfering RNA (siRNA)
      for CTP: choline phosphate cytidylyltranferase alpha (CCTalpha) (siRNA-CCTalpha).
      Results showed that survival was independent of dietary treatments (P>0.05).
      Weight gain and feed efficiency in the HL-HP group were significantly higher than
      in the LL-LP and HL-LP groups (P<0.05). High level of dietary PL could markedly
      reduce abnormal hepatic lipid accumulation induced by the HL-LP diet (P<0.05).
      Similarly, compared with the corresponding controls, a significant
      decrease/increase in lipid content was observed in primary hepatocytes incubated
      with PC/siRNA-CCTalpha (P<0.05). High level of dietary PL reversed the HL-LP diet
      induced increased levels of mRNA of fatty acid uptake and lipid synthesis related
      genes (P<0.05). In addition, High level of dietary PL markedly down-regulated the
      transcript levels of fatty acid oxidation-related genes and enhanced the
      transcript levels of VLDL assembly-related genes regardless of dietary lipid
      levels (P<0.05). Compared with corresponding controls, primary hepatocytes
      treated with PC showed significantly higher mRNA expression of lipid synthesis
      and VLDL assembly-related genes and lower mRNA expression of fatty acid oxidation
      related genes, with hepatocytes treated with siRNA-CCTalpha exhibiting the
      opposite trend (P<0.05). In summary, these results demonstrated that high level
      of dietary PL might reverse the HL-LP diet-induced abnormal lipid accumulation in
      the liver through inhibiting fatty acid uptake and lipid synthesis, together with
      promoting the lipid export at the transcriptional level. Lipid export-promoting
      effect of PC was confirmed by in vitro studies. The present study showed for the
      first time that PL or PC could influence various metabolic pathways to regulate
      hepatic lipid deposition in fish at least at the transcriptional level.

PMID- 29198194
TI  - The effects of diurnal Ramadan fasting on energy expenditure and substrate
      oxidation in healthy men.
AB  - The study aimed to examine the effects of diurnal Ramadan fasting (RF) on
      substrate oxidation, energy production, blood lipids and glucose as well as body
      composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non
      practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were
      additionally assessed at days 10, 20 and 30 of RF in the morning and evening.
      Body composition was determined by hydrodensitometry, substrate oxidation and
      energy production by indirect calorimetry, blood metabolic profile by biochemical
      analyses and energy balance by activity tracker recordings and food log analyses.
      A significant group*time interaction revealed that chronic RF reduced body mass
      and adiposity in FAST, without changing lean mass, whereas CNT subjects remained
      unchanged. In parallel to these findings, a significant main diurnal effect
      (morning v. evening) of RF on substrate oxidation (a shift towards lipid
      oxidation) and blood metabolic profile (a decrease in glucose and an increase in
      total cholesterol and TAG levels, respectively) was observed, which did not vary
      over the course of the Ramadan. In conclusion, although RF induces diurnal
      metabolic adjustments (morning v. evening), no carryover effect was observed
      throughout RF despite the extended daily fasting period (18.0 (sd 0.3) h) and
      changes in body composition.

PMID- 29198195
TI  - A severe gastroenteritis outbreak of Salmonella enterica serovar Enteritidis PT8,
      with PFGE profile XbaI.0024 and MLVA profile 2-9-7-3-2 following a christening
      reception, Greece, 2016.
AB  - In June 2016, a Salmonella enterica serovar Enteritidis outbreak (n = 56)
      occurred after a christening reception in Central Greece, mainly affecting
      previously healthy adults; one related death caused media attention. Patients
      suffered from profuse diarrhoea, fever and frequent vomiting episodes requiring
      prolonged hospitalisation and sick leave from work, with a 54% hospital admission
      rate. The majority of cases experienced serious illness within <12 h of attending
      the party. We investigated the outbreak to identify the source(s) of infection
      and contributing factors to the disease severity. From the retrospective cohort
      study, the cheesy penne pasta was the most likely vehicle of infection (relative
      risk 7.8; 95% confidence interval 3.6-16.8), explaining 79% of the cases. S.
      enterica ser. Enteritidis isolates were typed as phage-type PT8, pulsed-field gel
      electrophoresis type XbaI.0024, multiple locus variable-number tandem repeat
      analysis-type 2-9-7-3-2. The strain did not share the single-nucleotide
      polymorphism address of the concurrent European S. enterica ser. Enteritidis PT8
      outbreak clusters. Following five consecutive years with no documented S.
      enterica ser. Enteritidis outbreaks in Greece, this outbreak, likely associated
      with a virulent strain, prompted actions towards the enhancement of the national
      Salmonella molecular surveillance and control programmes including the
      intensification of training of food handlers for preventing similar outbreaks in
      the future. Advanced molecular techniques were useful in distinguishing unrelated
      outbreak strains.

PMID- 29198197
TI  - The incidence of very late-onset psychotic disorders: a systematic review and
      meta-analysis, 1960-2016.
AB  - A substantial subset of people with psychotic disorders are first diagnosed in
      old age, yet little is known about the epidemiology of very late-onset
      schizophrenia-like psychosis. We investigated the incidence of affective and non
      affective psychotic disorders in those aged 65 and above, and examined variation
      related to potential risk factors via systematic literature review. We searched
      PubMed, PsychInfo, Web of Science and bibliographies and directly contacted
      authors to obtain citations published between 1960 and 2016 containing
      (derivable) incidence data. Cases were those diagnosed with non-organic psychotic
      disorders after age 65. Findings were presented narratively, and random-effects
      meta-analyses were used to obtain pooled incidence rates. From 5687 citations, 41
      met inclusion criteria. The pooled incidence of: affective psychoses was 30.9 per
      100 000 person-years at risk (100 kpy) [95% confidence interval (CI) 11.5-83.4;
      I2 = 0.99], and schizophrenia was 7.5 per 100 kpy (95% CI 6.2-9.1; I2 = 0.99),
      with some evidence of higher schizophrenia rates in women [odds ratio (OR) = 1.6;
      95% CI 1.0-2.5, p = 0.05]. We found narrative evidence of increasing incidence
      rates of non-affective psychoses with age, and higher rates amongst migrants than
      baseline populations, but no evidence that incidence varied by study quality or
      case ascertainment period (quality OR = 1.04; 95% CI 0.74-1.48; time period OR =
      1.00; 95% CI 0.95-1.05). Substantial heterogeneity in the incidence of very late
      onset schizophrenia-like psychoses was observed. No identified studies examined
      possible risk factors which may account for such variation, including socio
      economic status, sensory impairment, traumatic life events, or social isolation.

PMID- 29198196
TI  - The identification and expression analysis of candidate chemosensory genes in the
      bird cherry-oat aphid Rhopalosiphum padi (L.).
AB  - The bird cherry-oat aphid Rhopalosiphum padi (L.) is one of the most important
      wheat pests with polyphagia and autumn migrants. And, chemosensory genes were
      thought to play a key role in insect searching their hosts, food and mate.
      However, a systematic identification of the chemosensory genes in this pest has
      not been reported. Thus, in this study, we identified 14 odorant-binding
      proteins, nine chemosensory proteins, one sensory neuron membrane protein, 15
      odorant receptors, 19 gustatory receptors and 16 ionotropic receptors from R.
      padi transcriptomes with a significantly similarity (E-value < 10-5) to known
      chemosensory genes in Acyrthosiphon pisum and Aphis gossypii. In addition, real
      time quantitative polymerase chain reaction (RT-qPCR) was employed to determine
      the expression profiles of obtained genes. Among these obtained genes, we
      selected 23 chemosensory genes to analyze their expression patterns in different
      tissues, wing morphs and host plants. We found that except RpOBP1, RpOBP3, RpOBP4
      and RpOBP5, the rest of the selected genes were highly expressed in the head with
      antennae compared with body without head and antennae. Besides that, the
      stimulation and depression of chemosensory genes by plant switch indicated that
      chemosensory genes might be involved in the plant suitability assessment. These
      results not only provide insights for the potential roles of chemosensory genes
      in plant search and perception of R. padi but also provide initial background
      information for the further research on the molecular mechanism of the polyphagia
      and autumn migrants of it. Furthermore, these chemosensory genes are also the
      candidate targets for pest management control in future.

PMID- 29198198
TI  - Assessing resistance of sugarcane varieties to sugarcane borer Diatraea
      saccharalis Fab. (Lepidoptera: Crambidae).
AB  - In this study, we investigated resistance traits to the sugarcane borer Diatraea
      saccharalis Fab. (Lepidoptera: Crambidae) in the leaves and stalks of six
      sugarcane cultivars in a series of greenhouse and laboratory assays.
      Investigation of plant factors and infestation rates to better discriminate stalk
      damage by the sugarcane borer indicated that infestation of 7-month-old, single
      plants with 20 larvae at the third or fourth instar per plant was suitable to
      assess tunneling length. Three cultivars (i.e. SP803280, RB928064, and RB835486)
      had lower stalk damage (i.e. tunnel length) than cultivar SP891115, which
      exhibited relatively greater susceptibility to tunneling by the borer. The time
      required for the larvae to enter the sugarcane stalk was longer for cultivar
      SP803280, indicating resistance traits on the stalk surface, which correlated
      with lower stalk damage. Larvae feeding on SP813250 stalks had the lowest weight
      gain, indicating that this cultivar has resistance traits to larval development
      within its stalks. Cultivars RB867515 and SP891115 resulted in the highest
      mortality of early-stage larvae feeding on leaves, indicating the presence of
      resistance factors in their leaves. Multi-trait cluster and principal component
      analyses placed the cultivars into three and four clusters, respectively. The
      cultivars placed in different groups that exhibited resistance to leaf feeding,
      stalk entrance, and tunneling by the sugarcane borer could be used for crossings
      in sugarcane breeding programs with the goal of obtaining higher levels of
      resistance to D. saccharalis.

PMID- 29198199
TI  - Secular trends in the prevalence of major and subthreshold depression among 55-64
      year olds over 20 years.
AB  - BACKGROUND: Studying secular trends in the exposure to risk and protective
      factors of depression and whether these trends are associated with secular trends
      in the prevalence of depression is important to estimate future healthcare
      demands and to identify targets for prevention. METHODS: Three birth cohorts of
      55-64-year olds from the population-based Longitudinal Aging Study Amsterdam were
      examined using identical methods in 1992 (n = 944), 2002 (n = 964) and 2012 (n =
      957). A two-stage screening design was used to identify subthreshold depression
      (SUBD) and major depressive disorder (MDD). Multinomial logistic regression
      analyses were used to identify secular trends in depression prevalence and to
      identify factors from the biopsychosocial domains of functioning that were
      associated with these trends. RESULTS: Compared with 1992, MDD became more
      prevalent in 2002 (OR 1.90, 95% CI 1.10-3.28, p = 0.022) and 2012 (OR 1.80, 95%
      CI 1.03-3.14, p = 0.039). This was largely attributable to an increase in the
      prevalence of chronic diseases and functional limitations. Socioeconomic and
      psychosocial improvements, including an increase in labor market participation,
      social support and mastery, hampered MDD rates to rise more and were also
      associated with a 32% decline of SUBD-rates in 2012 as compared with 2002 (OR
      0.68, 95% CI 0.48-0.96, p = 0.03). CONCLUSIONS: Among late middle-aged adults,
      there is a substantial net increase of MDD, which is associated with
      deteriorating physical health. If morbidity and disability continue to increase,
      a further expansion of MDD rates may be expected. Improving socioeconomic and
      psychosocial conditions may benefit public health, as these factors were
      protective against a higher prevalence of both MDD and SUBD.

PMID- 29198200
TI  - Selecting native perennial plants for ecological intensification in Mediterranean
      greenhouse horticulture.
AB  - Natural control by predators and parasitoids provides an important and often
      unnoticed ecosystem service to agricultural landscapes by reducing pest
      populations in crops. The current model of horticultural intensification in south
      eastern Spain produces high yields but has also resulted in a landscape almost
      completely covered by plastic. Promoting natural areas among greenhouses could
      enhance biodiversity, by being beneficial insects, and reduce pest pressure
      outdoors. The first step is to ascertain how pests and their natural enemies
      (NEs) use Mediterranean vegetation for selecting the best plants for pest
      suppression outdoors. The abundance of the two major horticultural pests, the
      tobacco whitefly, Bemisia tabaci, and the western flower thrips, Frankliniella
      occidentalis, together with their NEs, were assayed in 22 flowering perennial
      plants, which were newly planted in an experimental field surrounded by
      greenhouses. Eight plant species were identified as the most critical species for
      sustaining pest populations outdoors. A set of five plant species supported a
      medium level of pests, and another set of ten plant species supported the lowest
      level of both pests. Tobacco whitefly occurred in a few plants species, whereas
      western flower thrips occurred on almost all the plant species studied, and was
      favoured by the presence of flowers in perennial plants. The results suggest that
      plant diversity may provide relatively few acceptable host plants for tobacco
      whitefly than for western flower thrips. NEs were generally collected in plants
      that also supported abundance of pests, indicating that host/prey availability,
      more than food resources from flowers, was a stronger predictor of NE abundance
      in perennial plants. Field trials using the plants with the lowest host
      acceptance by pests are needed in order to ascertain whether pest abundance
      outdoors is reduced.

PMID- 29198201
TI  - Vitamin D in adolescence: evidence-based dietary requirements and implications
      for public health policy.
AB  - Vitamin D is a unique nutrient. First, it acts as a pro-hormone and secondly, the
      requirement for vitamin D can be met by both endogenous synthesis from sunlight
      and by dietary sources. This complicates the determination of dietary
      requirements for vitamin D, which along with the definition of optimal vitamin D
      status, have been highly controversial and much debated over recent years.
      Adolescents are a population group at high risk of low vitamin D status, which is
      concerning given the important role of vitamin D, and calcium, in promoting
      normal bone mineralisation and attainment of peak bone mass during this rapid
      growth phase. Dietary vitamin D recommendations are important from a public
      health perspective in helping to avoid deficiency and optimise vitamin D status
      for health. However limited experimental data from winter-based dose-response
      randomised trials in adolescents has hindered the development of evidence-based
      dietary requirements for vitamin D in this population group. This review will
      highlight how specifically designed randomised trials and the approach adopted
      for estimating such requirements can lead to improved recommendations. Such data
      indicate that vitamin D intakes of between 10 and about 30 ug/d may be required
      to avoid deficiency and ensure adequacy in adolescents, considerably greater than
      the current recommendations of 10-15 ug/d. Finally this review will consider the
      implications of this on public health policy, in terms of future refinements of
      vitamin D requirement recommendations and prioritisation of public health
      strategies to help prevent vitamin D deficiency.

PMID- 29198202
TI  - Effects of insecticides chlorpyrifos, emamectin benzoate and fipronil on
      Spodoptera litura might be mediated by OBPs and CSPs.
AB  - Spodoptera litura is a widespread polyphagous insect pest that can develop
      resistance and cross-resistance to insecticides, making it difficult to control.
      Insecticide exposure has previously been linked with induction of specific
      olfactory-related proteins, including some chemosensory proteins (CSPs) and
      odorant-binding proteins (OPBs), which may disrupt detection of environmental
      factors and reduce fitness. However, functional evidence supporting insecticide
      and OBPs/CSPs mediation remains unknown. Here we fed male S. litura moths with
      sucrose water containing one of three insecticides, chlorpyrifos, emamectin
      benzoate or fipronil, and used real-time quantitative polymerase chain reaction
      and RNAi to investigate OBPs and CSPs expression and their correlations with
      survival. Chlorpyrifos and emamectin benzoate increased expression of 78% of
      OBPs, plus 63 and 56% of CSP genes, respectively, indicating a major impact on
      these gene families. RNAi knockdown of SlituCSP18, followed by feeding with
      chlorpyrifos or fipronil, decreased survival rates of male moths significantly
      compared with controls. Survival rate also decreased significantly with the
      downregulation of SlituOBP9 followed by feeding with chlorpyrifos. Thus, although
      these three insecticides had different effects on OBP and CSP gene expression, we
      hypothesize that SlituOBPs and SlituCSPs might mediate their effects by
      increasing their expression levels to improve survival. Moreover, the
      differential response of S. litura male moths to the three insecticides indicated
      the potential specificity of chlorpyrifos affect SlituCSP18 and SlituOBP9
      expression.

PMID- 29198203
TI  - Blastoschizomyces capitatus pulmonary infections in immunocompetent patients:
      case report, case series and literature review.
AB  - Blastoschizomyces capitatus is an uncommon opportunistic yeast associated with
      infections in neutropaenic patients secondary to haematological malignancies,
      with a special predilection for the lungs. Globalisation and population migration
      impact on the epidemiology of infection with this organism but its effect on the
      immunocompetent population has rarely been described. We present here a case
      report, an overview of 11 other cases published between 2000 and 2016, and a
      comprehensive literature review of Blastoschizomyces pneumonia in the non
      immunocompromised. The median age at diagnosis was 68 years (range 40-86 years)
      and more than half the cases reported a positive history of either current or
      past tobacco smoking. Six cases had either clinical or radiological evidence of
      chronic obstructive pulmonary disease and three had a history of prior treated
      tuberculosis. Fluconazole and itraconazole, alone or in combination, was the most
      utilised treatment. We conclude that unlike most other invasive yeast species, B.
      capitatus poses an infectious risk for immunocompetent patients, usually of
      middle to older age with risk factors for distorted lung architecture. Further
      research is warranted into the pathophysiology of Blastoschizomyces infections in
      the immunocompetent, including standardised treatment options.

PMID- 29198205
TI  - Do mothers really know best? Complexities in testing the preference-performance
      hypothesis in polyphagous frugivorous fruit flies.
AB  - The preference-performance hypothesis (PPH) has widely been used to explain host
      exploitation patterns by phytophagous insects. However, this hypothesis often
      fails in the case of polyphagous species when compared with specialists. One
      explanation, validated by the information-processing hypothesis (IPH), considers
      that polyphagous insects are unable to process a large array of cues, which
      hinders females from distinguishing between high- and low- quality hosts. Here we
      analyzed Anastrepha ludens female host preference and offspring performance, and
      tested if neuronal limitations could possibly play a role in the incapacity of
      the polyphagous A. ludens to make 'accurate decisions' and therefore partially
      explain mismatches related to PPH. Results testing the PPH by correlating female
      preference to six naturally occurring hosts and its offspring outcomes show that
      A. ludens females oviposited greater proportions of eggs on fruit according to
      hierarchical preferences. Infestation level was low in white sapote, the
      preferential and seemingly putative ancestral host, likely due to sapote defence
      mechanisms. Pupal weight and adult size were lower when A. ludens larvae
      developed in guava (conditional host that was artificially infested) and peach, a
      lower ranked host compared with 'Marsh' grapefruit, white sapote, and 'Manila'
      mango (three preferred hosts). Larvae reared in 'Manzano' pepper, a low-ranked
      host, performed better than in peach and guava. Results testing the IPH, show
      that polyphagous A. ludens females were less accurate when discerning between a
      non natural host (guava) when compared with a preferred, natural host
      (grapefruit): error rate was significantly higher, number of oviposited fruit in
      a 6-h period was extremely low, time searching and ovipositing took longer, and
      pupae recovery was extremely low. Our findings indicate that both hypotheses
      tested are complementary and help better understand host use by A. ludens.
      However, we also discuss the complexity of polyphagy considering other factors
      such as plant resistance/defence mechanisms which are not fully addressed in both
      theories tested.

PMID- 29198206
TI  - THE DYNAMIC INTER-RELATIONSHIP BETWEEN OBESITY AND SCHOOL PERFORMANCE: NEW
      EMPIRICAL EVIDENCE FROM AUSTRALIA.
AB  - SummaryThis paper proposes a new empirical model for examining the relationship
      between obesity and school performance using the simultaneous equation modelling
      approach. The lagged effects of both learning and health outcomes were included
      to capture both the dynamic and inter-relational aspects of the relationship
      between obesity and school performance. The empirical application of this study
      used comprehensive data from the first five waves of the Longitudinal Study of
      Australian Children (LSAC), which commenced in 2004 (wave 1) and was repeated
      every two years until 2018. The study sample included 10,000 children, equally
      divided between two cohorts (infants and children) across Australia. The
      empirical results show that past learning and obesity status are strongly
      associated with most indicators of school outcomes, including reading, writing,
      spelling, grammar and numeracy national tests, and scores from the
      internationally standardized Peabody Picture Vocabulary Test and the Matrix
      Reasoning Test. The main findings of this study are robust due to the choice of
      obesity indicator and estimation methods.

PMID- 29198204
TI  - Assessing the evidence for shared genetic risks across psychiatric disorders and
      traits.
AB  - Genetic influences play a significant role in risk for psychiatric disorders,
      prompting numerous endeavors to further understand their underlying genetic
      architecture. In this paper, we summarize and review evidence from traditional
      twin studies and more recent genome-wide molecular genetic analyses regarding two
      important issues that have proven particularly informative for psychiatric
      genetic research. First, emerging results are beginning to suggest that genetic
      risk factors for some (but not all) clinically diagnosed psychiatric disorders or
      extreme manifestations of psychiatric traits in the population share genetic
      risks with quantitative variation in milder traits of the same disorder
      throughout the general population. Second, there is now evidence for substantial
      sharing of genetic risks across different psychiatric disorders. This extends to
      the level of characteristic traits throughout the population, with which some
      clinical disorders also share genetic risks. In this review, we summarize and
      evaluate the evidence for these two issues, for a range of psychiatric disorders.
      We then critically appraise putative interpretations regarding the potential
      meaning of genetic correlation across psychiatric phenotypes. We highlight
      several new methods and studies which are already using these insights into the
      genetic architecture of psychiatric disorders to gain additional understanding
      regarding the underlying biology of these disorders. We conclude by outlining
      opportunities for future research in this area.

PMID- 29198207
TI  - Neuroanatomical changes in people with high schizotypy: relationship to glutamate
      levels.
AB  - BACKGROUND: Cortical glutamatergic dysfunction is thought to be fundamental for
      psychosis development, and may lead to structural degeneration through
      excitotoxicity. Glutamate levels have been related to gray matter volume (GMV)
      alterations in people at ultra-high risk of psychosis, and we previously reported
      GMV changes in individuals with high schizotypy (HS), which refers to the
      expression of schizophrenia-like characteristics in healthy people. This study
      sought to examine whether GMV changes in HS subjects are related to glutamate
      levels. METHODS: We selected 22 healthy subjects with HS and 23 healthy subjects
      with low schizotypy (LS) based on their rating on a self-report questionnaire for
      psychotic-like experiences. Glutamate levels were measured in the bilateral
      anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and
      GMV was assessed using voxel-based morphometry. RESULTS: Subjects with HS showed
      GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045).
      Significant increases in GMV were also detected in HS, in the precuneus (pFWE =
      0.043), thereby replicating our previous finding in a separate cohort, as well as
      in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC
      glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC
      GMV (pFWE = 0.026). Such association was absent in LS. CONCLUSIONS: Our study
      shows that GMV findings in schizotypy are related to glutamate levels, supporting
      the hypothesis that glutamatergic function may lead to structural changes
      associated with the expression of psychotic-like experiences.

PMID- 29198209
TI  - Speech sound characteristics of early words: influence of phonological factors
      across vocabulary development.
AB  - This study investigates whether the earliest words children choose to say are
      mainly words containing sounds they can produce (cf. 'phonological dominance'
      hypotheses), or whether children choose words without regard to their
      phonological characteristics (cf. 'lexical dominance' hypotheses). Phonological
      properties of words in spontaneous speech from six children age 0;8 to 2;11 were
      analyzed by comparing sound distributions of consonant place and manner. Word
      initial and word-final consonant patterns in children's Word Targets versus
      Actual Word Forms were analyzed as a function of vocabulary size. Word-initial
      results showed more overall evidence for phonological dominance. In word-final
      position, at lower vocabulary sizes, results showed several differences between
      Word Targets and Actual Word Forms, consistent with lexical dominance. These
      findings challenge an 'either-or' phonological versus lexical dominance approach,
      and support consideration of a multifactorial set of influences, including
      different phonological dimensions and word positions, on the words that young
      children choose to say.

PMID- 29198208
TI  - Association between childhood infection, serum inflammatory markers and
      intelligence: findings from a population-based prospective birth cohort study.
AB  - A link between infection, inflammation, neurodevelopment and adult illnesses has
      been proposed. The objective of this study was to examine the association between
      infection burden during childhood - a critical period of development for the
      immune and nervous systems - and subsequent systemic inflammatory markers and
      general intelligence. In the Avon Longitudinal Study of Parents and Children, a
      prospective birth cohort in England, we examined the association of exposure to
      infections during childhood, assessed at seven follow-ups between age 1.5 and 7.5
      years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP)
      levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the
      relationship between inflammatory markers and IQ. Very high infection burden (90+
      percentile) was associated with higher CRP levels, but this relationship was
      explained by body mass index (adjusted odds ratio (OR) 1.19; 95% confidence
      interval (CI) 0.95-1.50), maternal occupation (adjusted OR 1.23; 95% CI 0.98
      1.55) and atopic disorders (adjusted OR 1.24; 95% CI 0.98-1.55). Higher CRP
      levels were associated with lower IQ; adjusted beta = -0.79 (95% CI -1.31 to 
      0.27); P = 0.003. There was no strong evidence for an association between
      infection and IQ. The findings indicate that childhood infections do not have an
      independent, lasting effect on circulating inflammatory marker levels
      subsequently in childhood; however, elevated inflammatory markers may be harmful
      for intellectual development/function.

PMID- 29198210
TI  - Sustainable diet policy development: implications of multi-criteria and other
      approaches, 2008-2017.
AB  - The objective of the present paper is to draw lessons from policy development on
      sustainable diets. It considers the emergence of sustainable diets as a policy
      issue and reviews the environmental challenge to nutrition science as to what a
      'good' diet is for contemporary policy. It explores the variations in how
      sustainable diets have been approached by policy-makers. The paper considers how
      international United Nations and European Union (EU) policy engagement now
      centres on the 2015 Sustainable Development Goals and Paris Climate Change
      Accord, which require changes across food systems. The paper outlines national
      sustainable diet policy in various countries: Australia, Brazil, France, the
      Netherlands, Qatar, Sweden, UK and USA. While no overarching common framework for
      sustainable diets has appeared, a policy typology of lessons for sustainable
      diets is proposed, differentiating (a) orientation and focus, (b) engagement
      styles and (c) modes of leadership. The paper considers the particularly tortuous
      rise and fall of UK governmental interest in sustainable diet advice. Initial
      engagement in the 2000s turned to disengagement in the 2010s, yet some advice has
      emerged. The 2016 referendum to leave the EU has created a new period of policy
      uncertainty for the UK food system. This might marginalise attempts to generate
      sustainable diet advice, but could also be an opportunity for sustainable diets
      to be a goal for a sustainable UK food system. The role of nutritionists and
      other food science professions will be significant in this period of policy flux.

PMID- 29198211
TI  - Association of Cx43 rs2071166 polymorphism with an increased risk for atrial
      septal defect.
AB  - Atrial septal defect is one of the most common CHD. The pathogenesis of atrial
      septal defect still remains unknown. Cx43 is the most prevalent connexin in the
      mammalian heart during development. Its genetic variants can cause several CHD.
      The aim of our study was to investigate the association of genetic variations of
      the Cx43 with sporadic atrial septal defect. A total of 450 paediatric patients
      were recruited, including 150 cases with atrial septal defect and 300 healthy
      controls. The promoter region of Cx43 was analysed by sequencing after polymerase
      chain reaction. All data were analysed by using the Statistic Package for Social
      Science 19.0 software. The frequency of the single nucleotide polymorphism
      rs2071166 was significantly higher in atrial septal defect cases than in healthy
      controls. The CC genotype at rs2071166 site in Cx43 was correlated with an
      increased risk for atrial septal defect (p<0.0001, odds ratio=3.891, 95%
      confidence interval 1.948-7.772) and the C allele was positively correlated with
      atrial septal defect (p=0.007, odds ratio=1.567, 95% confidence interval 1.129
      2.175). In conclusion, our results confirmed that rs2071166 in Cx43 may be
      relevant with an increased atrial septal defect risk.

PMID- 29198212
TI  - Rubella vaccination in India: identifying broad consequences of vaccine
      introduction and key knowledge gaps.
AB  - Rubella virus infection typically presents as a mild illness in children;
      however, infection during pregnancy may cause the birth of an infant with
      congenital rubella syndrome (CRS). As of February 2017, India began introducing
      rubella-containing vaccine (RCV) into the public-sector childhood vaccination
      programme. Low-level RCV coverage among children over several years can result in
      an increase in CRS incidence by increasing the average age of infection without
      sufficiently reducing rubella incidence. We evaluated the impact of RCV
      introduction on CRS incidence across India's heterogeneous demographic and
      epidemiological contexts. We used a deterministic age-structured model that
      reflects Indian states' rural and urban area-specific demography and vaccination
      coverage levels to simulate rubella dynamics and estimate CRS incidence with and
      without RCV introduction to the public sector. Our analysis suggests that current
      low-level private-sector vaccination has already slightly increased the burden of
      CRS in India. We additionally found that the effect of public-sector RCV
      introduction depends on the basic reproductive number, R 0, of rubella. If R 0 is
      five, a value empirically estimated from an array of settings, CRS incidence post
      RCV introduction will likely decrease. However, if R 0 is seven or nine, some
      states may experience short-term or annual increases in CRS, even if a long-term
      total reduction in cases (30 years) is expected. Investment in population-based
      serological surveys and India's fever/rash surveillance system will be key to
      monitoring the success of the vaccination programme.

PMID- 29198213
TI  - Presence of neuroticism and antidepressant remission rates in late-life
      depression: results from the Neurobiology of Late-Life Depression (NBOLD) study.
AB  - ABSTRACTNeuroticism in older adults is common yet understudied, particularly its
      effects on depression treatment outcomes. We hypothesized that presence of high
      neuroticism would be associated with lower 12-week remission rates in older
      depressed sertraline-treated patients. In this longitudinal cohort study, 43
      depressed older adults completed the Revised NEO Personality Inventory (NEO PI
      R). A study psychiatrist administered the Montgomery Asberg Depression Rating
      Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of
      medical burden) at baseline, and the MADRS at each clinical visit. All subjects
      began open-label sertraline treatment and were followed over 12 weeks with
      clinically indicated flexible dosing and an option to switch antidepressants. We
      used regression analyses to examine factors related to 12-week remission of
      depression (MADRS score < 8) and final MADRS score. We found that higher total
      neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000)
      and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728
      0.983), were associated with lower likelihood of remission among both the
      intention-to-treat group and sertraline completers. Findings remained significant
      after controlling for baseline MADRS and CIRS score. In conclusion, assessment of
      personality, particularly features of neuroticism, may be important in management
      of late-life depression. Future studies should determine if depressed patients
      high in neuroticism may benefit from psychotherapy focusing on emotional
      regulation and stress management.

PMID- 29198214
TI  - Teachers' Perceived Disruption at School and Related Variables from Teachers and
      School Functioning.
AB  - This study explores variables related to teachers' perception of disruption at
      school as a function of teachers (sense of personal accomplishment, professional
      disengagement and depersonalization and emotional exhaustion) and school (overall
      school management and quality of school rules) factors. Using a questionnaire
      regarding school climate, data from 4,055 teachers across 187 high schools were
      analyzed. Hierarchical linear modeling was applied and the results indicate that,
      taken separately, significant individual teacher predictors (Model 1) explain 26%
      (95% CI [.23, .29]) of the variability of the perceived disruption, especially
      depersonalization and emotional exhaustion. Contextual school variables (Model 2)
      explained 15% (95% CI [.12, .18]) of variance in teachers' perceived disruption,
      with a significant negative relationship with the quality of rules. Model 3
      included the above factors plus interactions between the emotional exhaustion and
      depersonalization variables and school indicators (30% of variance explained; 95%
      CI [.26, .33]). The results indicated the existence of a moderating effect for
      the quality of school rules, so that fair and properly-applied rules in the
      school context may be associated with a decrease in the relationship between
      depersonalization and emotional exhaustion and perceived disruption.

PMID- 29198215
TI  - Dietary l-arginine supplementation improves semen quality and libido of boars
      under high ambient temperature.
AB  - l-Arginine is a nutritionally essential amino acid for spermatogenesis and plays
      versatile roles in animal health and can be utilized as a potential agent to
      improve reproductive performance of boars under high ambient temperature. The
      present study aimed to determine whether dietary l-arginine could alleviate heat
      stress-induced infertility in boars. In all, 20 boars (PIC 1040; 248.59+/-3.84 kg
      BW and 407.65+/-6.40 days of age) were selected and randomly assigned to four
      groups (group 0.0%, basal diet; group 0.6%, 0.8% or 1.0%, basal diet added with
      0.6%, 0.8% or 1.0% l-arginine (wt:wt), respectively.) The four diets were made
      isonitrogenous by addition of appropriate amounts of l-alanine. Boars were pre
      fed the corresponding experimental diet for 42 days. Then, the semen
      characteristics and libido were accessed for 6 weeks during the hot summer period
      (25.5 degrees  to 33.0 degrees C). Results show that dietary l-arginine
      remarkably improved sperm motility, normality, total sperm number and effective
      total sperm number. Also, dietary l-arginine improved semen antioxidant capacity,
      such as decrease of malondialdehyde and 8-Hydroxy-2'-deoxyguanosine content in
      sperm (P<0.05), increase of the ratio of glutathione and oxidized glutathione,
      total antioxidant capacity, glutathione peroxidase and catalase activities in
      seminal plasma (P<0.05). Most of mitochondria contained intact ultrastructure in
      l-arginine-supplemented group which also accompany with higher ATP content than
      the 0.0% group. The boars fed 0.8% l-arginine show increased levels of estradiol
      17beta and testosterone and exhibit improved libido performance than boars in the
      0.0% group. Adding dietary l-arginine linearly increased (P=0.002) nitric oxide
      content (as l-arginine increased). The scrotal surface temperature in the 0.6%,
      0.8% and 1.0% group were decreased by 0.9 degrees C, 0.9 degrees C and 0.4
      degrees C, respectively, compared with the 0.0% group. l-Arginine levels caused
      linear effect on semen quality and antioxidant capacity, also caused quadratic
      effect on libido performance. During the hot summer months, the predicted optimal
      l-arginine levels for best semen quality and antioxidant capacity was 0.8% to
      1.0% and for best libido performance was 0.8%. It can be concluded that l
      arginine can be used as an effective agent to alleviate heat stress-induced
      infertility of boar, and that 0.8% to 1.0% can be considered as the optimum
      dosage.

PMID- 29198216
TI  - Word and Nonword Repetition Abilities in Spanish Language: Longitudinal Evidence
      from Typically Developing and Late Talking Children.
AB  - This longitudinal study examined the early word and nonword repetition abilities
      of monolingual Spanish speaking children. We explored the role that word status,
      word length, and time play in repetition performance of children with different
      vocabulary levels. We also examined the predictive value of vocabulary level in
      repetition abilities. Thirty-seven children participated in this study: 15 late
      talkers and 22 typically developing children. Families completed the Spanish
      version of the MacArthur Communicative Developmental Inventory (MCDI) at age 2;
      children performed a word and nonword repetition task at three different moments,
      with a temporal interval of 6 months between Time 1 and Time 2, and eight months
      between Time 2 and Time 3, periods during which linguistic development takes
      place. We found significant effects for word status, word length, vocabulary
      level and time: words are repeated better than nonwords; one syllable items are
      easier to repeat than two and three syllable ones; the performance of late
      talking children is lower compared to typically developing children throughout
      the study; and repetition abilities improve longitudinally. In addition, early
      vocabulary level predicts subsequent repetition abilities and early nonword
      repetition abilities predict future nonword repetition performance.

PMID- 29198217
TI  - What Does It Take to Search Organized? The Cognitive Correlates of Search
      Organization During Cancellation After Stroke.
AB  - OBJECTIVES: Stroke could lead to deficits in organization of visual search.
      Cancellation tests are frequently used in standard neuropsychological assessment
      and appear suitable to measure search organization. The current aim was to
      evaluate which cognitive functions are associated with cancellation organization
      measures after stroke. METHODS: Stroke patients admitted to inpatient
      rehabilitation were included in this retrospective study. We performed
      exploratory factor analyses to explore cognitive domains. A digital shape
      cancellation test (SC) was administered, and measures of search organization
      (intersections rate and best r) were computed. The following cognitive functions
      were measured by neuropsychological testing: neglect (SC, line bisection; LB,
      Catherine Bergego Scale; CBS, and Balloons Test), visuospatial perception and
      construction (Rey Complex Figure Test, RCFT), psychomotor speed (Trail Making
      Test; TMT-A), executive functioning/working memory (TMT-B), spatial planning
      (Tower Test), rule learning (Brixton Test), short-term auditory memory (Digit
      Span Forward; DSF), and verbal working memory (Digit Span Backward; DSB).
      RESULTS: In total, 439 stroke patients were included in our analyses. Four
      clusters were separated: "Executive functioning" (TMT-A, TMT-B, Brixton Test, and
      Tower Test), "Verbal memory" (DSF and DSB), "Search organization" (intersections
      rate and best r), and "Neglect" (CBS, RCFT copy, Balloons Test, SC, and LB).
      CONCLUSIONS: Search organization during cancellation, as measured with
      intersections rate and best r, seems a distinct cognitive construct compared to
      existing cognitive domains that are tested during neuropsychological assessment.
      Administering cancellation tests and analyzing measures of search organization
      could provide useful additional insights into the visuospatial processes of
      stroke patients. (JINS, 2018, 24, 424-436).

PMID- 29198218
TI  - PASTRAB: a model for simulating intake regulation and growth of rabbits raised on
      pastures.
AB  - Given the very recent investment in research on organic rabbit production, many
      knowledge gaps remain. Simulation models based on data from experiments and farms
      may help generate general principles for organic rabbit production. Our goals
      were to (i) develop a model to simulate intake regulation and growth of rabbits
      raised on pastures, (ii) validate this model under a diversity of conditions and
      (iii) conduct a simulation experiment to predict the potential to decrease the
      supply of complete feed by increasing the grazing area per rabbit. The model
      developed (PASTRAB) simulates organic rabbit fattening on pastures in four main
      submodels that represent dynamics of (i) herbage standing biomass, fill and feed
      values; (ii) intake of herbage, complementary feed (i.e. complete pellets, cereal
      legume grain mixtures) and hay as regulated by herbage allowance, fill and feed
      values of feedstuffs and rabbit physiological parameters; (iii) conversion of
      rabbit intake into live weight gain; and (iv) rabbit mortality. The model also
      calculates gross margin per rabbit sold. Model accuracy was assessed by
      considering the fit between observed and predicted herbage intake, which was low,
      with a relative root mean square error (rRMSE) of 51% and 66% on grass-based and
      legume-based pastures, respectively. However, the standard deviations of observed
      herbage intake were similar to the root mean square error of predicted herbage
      intake, indicating that it would have been difficult to improve model
      calibration. The fit between observed and predicted rabbit live weight was
      acceptable, with an rRMSE of 11% and 10% for grass-based and legume-based
      pastures, respectively. Simulated scenarios showed that a decrease in
      complementary feed combined with an increase in the grazing area per rabbit had
      little impact on average daily growth and gross margin per rabbit but increased
      herbage use efficiency. With 90 g of complementary feed per day and grazing of
      0.4 m2/rabbit per day, herbage use efficiency was 22%, with average daily growth
      of 21.6 g/day and gross margin of 18.80 ?/rabbit. With no complementary feed and
      grazing of 1.2 m2/rabbit per day, average daily growth decreased (19.2 g/day),
      but herbage use efficiency reached 100% and gross margin reached 19.20 ?/rabbit.
      We used PASTRAB in participatory workshops with farmers so that the latter could
      explore adaptations to their current practices. Overall, farmers considered the
      model predictions realistic, and some of them decided to adapt some of their
      management practices immediately after the workshops.

PMID- 29198219
TI  - Unravelling the physical, technological and economic factors driving the
      intensification trajectories of livestock systems.
AB  - Over the past 100 years, the French livestock sector has experienced significant
      intensification that has occurred in different ways across the country.
      Specifically, France has changed from a homogeneous state with most of the
      agricultural area covered by grasslands and a uniform distribution of animals, to
      a heterogeneous state characterised by an uneven distribution of grasslands,
      livestock numbers and livestock species. Studying the dynamics of this change is
      fundamental to the identification of drivers that shaped the various
      intensification trajectories and led to these different states, as well as to the
      prediction of future changes. Hence, the objective of this study was to
      characterise the trajectories undertaken by the French livestock sector to
      understand the intensification process and the role of socioeconomic, land use
      and production-related factors. A set of 10 indicators was employed to analyse
      the main changes between 1938 and 2010, using principal component analysis
      followed by a clustering of the 88 French departments. Between 1938 and 2010,
      significant increases in farm size, mechanisation, labour productivity and the
      stocking rates of monogastrics enabled the French livestock sector to double its
      production. The most important changes involved mechanisation (with the number of
      tractors per hectare (ha) rising from 0.0012 to 0.0053), labour productivity
      (improving from 8.6 to 35.9 ha/worker), livestock production (e.g. milk
      production increasing from 758 to 1856 l/ha of fodder area) and stocking rates
      (rising from 0.57 to 0.98 livestock units (LU) per ha). The increased
      heterogeneity apparent in the patterns of change throughout France's departments
      was captured by clustering four trajectories. Two trajectories were formed by
      departments that experienced strong specialisation towards livestock production,
      with one type mainly orientated towards high-intensive dairy, poultry and pig
      landless production systems, and a second type orientated towards extensive beef
      grazing production systems. Another trajectory corresponded to departments that
      specialised in crop production with high labour productivity; mixed crop
      livestock systems were still maintained at the margins of this group of
      departments. The fourth trajectory corresponded to the lowest livestock
      population and productivity levels. The increase in mechanisation during the
      period was important but uniform, with no significant differences between the
      trajectories. This typology of intensification trajectories will enable the
      targeting of specific areas in which the detrimental impacts of livestock
      intensification require mitigation and provide guidance for future livestock
      sector developments.

PMID- 29198220
TI  - Meeting UK dietary recommendations is associated with higher estimated consumer
      food costs: an analysis using the National Diet and Nutrition Survey and consumer
      expenditure data, 2008-2012.
AB  - OBJECTIVE: To test whether diets achieving recommendations from the UK's
      Scientific Advisory Committee on Nutrition (SACN) were associated with higher
      monetary costs in a nationally representative sample of UK adults. DESIGN: A
      cross-sectional study linking 4 d diet diaries in the National Diet and Nutrition
      Survey (NDNS) to contemporaneous food price data from a market research firm. The
      monetary cost of diets was assessed in relation to whether or not they met eight
      food- and nutrient-based recommendations from SACN. Regression models adjusted
      for potential confounding factors. The primary outcome measure was individual
      dietary cost per day and per 2000 kcal (8368 kJ). SETTING: UK. SUBJECTS: Adults
      (n 2045) sampled between 2008 and 2012 in the NDNS. RESULTS: On an isoenergetic
      basis, diets that met the recommendations for fruit and vegetables, oily fish,
      non-milk extrinsic sugars, fat, saturated fat and salt were estimated to be
      between 3 and 17 % more expensive. Diets meeting the recommendation for red and
      processed meats were 4 % less expensive, while meeting the recommendation for
      fibre was cost-neutral. Meeting multiple targets was also associated with higher
      costs; on average, diets meeting six or more SACN recommendations were estimated
      to be 29 % more costly than isoenergetic diets that met no recommendations.
      CONCLUSIONS: Food costs may be a population-level barrier limiting the adoption
      of dietary recommendations in the UK. Future research should focus on identifying
      systems- and individual-level strategies to enable consumers achieve dietary
      recommendations without increasing food costs. Such strategies may improve the
      uptake of healthy eating in the population.

PMID- 29198221
TI  - Person-centered care in Norwegian nursing homes and its relation to
      organizational factors and staff characteristics: a cross-sectional survey.
AB  - : ABSTRACTBackground:Person-centered care (PCC) is regarded as good quality care
      for persons with dementia. This study aimed to explore and understand the
      association between PCC and organizational, staff and unit characteristics in
      nursing homes (NHs). METHODS: Staff from 175 NH units in Norway (n = 1,161)
      completed a survey, including measures of PCC and questions about staff
      characteristics and work-related psychosocial factors. In addition, data about
      organizational and structural factors and assessment of the physical environment
      in the units were obtained. The distribution of these factors in regular units
      (RUs) and special care units (SCUs) is described, and the differences between the
      two types of units are analyzed. Furthermore, multilevel linear regression
      analyses explored the extent to which variables were associated with PCC.
      RESULTS: Higher levels of PCC were associated with a greater job satisfaction,
      three years or more of health-related education, a lower level of quantitative
      demands and role conflict, a higher level of perception of mastery, empowering
      leadership, innovative climate and perception of group work, in addition to the
      type of unit and the physical environment in the NH unit designed for people with
      dementia. SCU and staff job satisfaction explained most of the variation in PCC.
      CONCLUSION: This study shows an association between PCC and organizational, staff
      and unit characteristics in NH. These findings indicate that providing PCC in NH
      care is closely linked to how the staff experiences their job situation in
      addition to both organizational and structural factors and the physical
      environment. Attention needs to be given to such factors when planning NH care.

PMID- 29198222
TI  - Epinephrine syringe exchange events in a paediatric cardiovascular ICU: analysing
      the storm.
AB  - : Introduction Haemodynamically unstable patients can experience potentially
      hazardous changes in vital signs related to the exchange of depleted syringes of
      epinephrine to full syringes. The purpose was to determine the measured effects
      of epinephrine syringe exchanges on the magnitude, duration, and frequency of
      haemodynamic disturbances in the hour after an exchange event (study) relative to
      the hours before (control). Materials and methods Beat-to-beat vital signs
      recorded every 2 seconds from bedside monitors for patients admitted to the
      paediatric cardiovascular ICU of Texas Children's Hospital were collected between
      1 January, 2013 and 30 June, 2015. Epinephrine syringe exchanges without
      dose/flow change were obtained from electronic records. Time, magnitude, and
      duration of changes in systolic blood pressure and heart rate were characterised
      using Matlab. Significant haemodynamic events were identified and compared with
      control data. RESULTS: In all, 1042 syringe exchange events were found and 850
      (81.6%) had uncorrupted data for analysis. A total of 744 (87.5%) exchanges had
      at least 1 associated haemodynamic perturbation including 2958 systolic blood
      pressure and 1747 heart-rate changes. Heart-rate perturbations occurred 37%
      before exchange and 63% after exchange, and 37% of systolic blood pressure
      perturbations happened before syringe exchange, whereas 63% occurred after
      syringe exchange with significant differences found in systolic blood pressure
      frequency (p<0.001), duration (p<0.001), and amplitude (p<0.001) compared with
      control data. CONCLUSIONS: This novel data collection and signal processing
      analysis showed a significant increase in frequency, duration, and magnitude of
      systolic blood pressure perturbations surrounding epinephrine syringe exchange
      events.

PMID- 29198223
TI  - Ibuprofen and indomethacin differentially regulate vascular endothelial growth
      factor and its receptors in ductus arteriosus endothelial cells.
AB  - BACKGROUND: Cyclooxygenase inhibitors are widely applied to facilitate ductal
      closure in preterm infants. The mechanisms that lead to patent ductus arteriosus
      closure are incompletely understood. Vascular endothelial growth factor plays
      pivotal roles during ductal closure and remodelling. Aim The aim of this study
      was to investigate the effects of ibuprofen and indomethacin on the expression of
      vascular endothelial growth factor and its receptors in a primary rat ductus
      arteriosus endothelial cell culture. METHODS: Protein expression of vascular
      endothelial growth factor and vascular endothelial growth factor receptor 1 and 2
      was confirmed in rat ductus arteriosus and aorta by immunofluorescence staining.
      Fetal rat endothelial cells were isolated from ductus arteriosus and aorta using
      immunomagnetic cell sorting and treated with ibuprofen or indomethacin. mRNA
      expression levels were assessed by quantitative polymerase chain reaction
      analysis. RESULTS: In ductal endothelial cells, ibuprofen significantly induced
      vascular endothelial growth factor and its receptor 2, but not receptor 1,
      whereas indomethacin did not alter the expression levels of the vascular
      endothelial growth factor system. In contrast, ibuprofen significantly induced
      vascular endothelial growth factor and its receptors 1 and 2 in aortic
      endothelial cells, whereas indomethacin only induced vascular endothelial growth
      factor receptor 2. CONCLUSION: Our results indicate differential effects of
      ibuprofen and indomethacin on the expression levels of the vascular endothelial
      growth factor system in ductus arteriosus endothelial cells. In addition, vessel
      specific differences between ductal and aortic endothelial cells were found.
      Further in vivo studies are needed to elucidate the biological significance of
      these findings.

PMID- 29198224
TI  - Case report and review of the literature: the utilisation of a ventricular assist
      device as bridge to recovery for anthracycline-induced ventricular dysfunction.
AB  - Ventricular assist devices are used in children with heart failure as a bridge to
      myocardial recovery or cardiac transplantation. Anthracyclines cause cardiac
      toxicity and may result in acute or long-term cardiac failure. We describe the
      use of a ventricular assist device as a bridge to recovery in a child with severe
      acute anthracycline-induced cardiomyopathy, and we review the associated
      literature. A 6-year-old girl was treated for acute myeloblastic leukaemia with
      daunorubicin and mitoxantrone. After 2 weeks her final dose of chemotherapy, her
      Left Ventricular Ejection Fraction decreased to 21%. Despite initiation of
      medical therapy, she had continued deterioration of left ventricular function and
      developed evidence of poor end-organ perfusion. She was not a candidate for
      cardiac transplantation, as the post-transplant immune suppression therapy would
      put her at risk for recurrence of her malignancy. We placed her on a short-term
      ventricular assist device as a bridge to ultimately placing her on a long-term
      ventricular assist device versus continuing medical therapy. Her left ventricular
      ejection fraction improved to 55% 24 days after ventricular assist device
      insertion. She was separated from the ventricular assist device 26 days after its
      insertion. She was discharged home 29 days later and is now 28 months after
      ventricular assist device implantation with stable ventricular function, as
      documented by a left ventricular ejection fraction of 55%, and normal end organ
      function. This case is one of the only reports known describing successful use of
      a short-term ventricular assist device as a bridge to recovery in a child with
      severe acute anthracycline-induced cardiotoxicity.

PMID- 29198225
TI  - A pilot study exploring staff acceptability of a socially assistive robot in a
      residential care facility that accommodates people under 65 years old.
AB  - ABSTRACTSocially assistive robots have successfully been trialed in residential
      care facilities (RCFs) for older adults. These robots may have potential for
      younger adults (i.e. under 65 years old) who also live in RCFs. However, it is
      important to investigate staff acceptability and ease-of-use of these robots.
      This pilot study used the Technology Acceptance Model to investigate how staff
      working in a specialized RCF for younger adults accept Betty, a socially
      assistive robot who was introduced in the facility for 12 weeks. Twenty-four
      staff completed pre-questionnaires, reporting that they thought Betty would have
      the ability to engage and entertain the residents they cared for. While there
      were only eight staff who completed the post-questionnaires, there were
      significant improvements compared to the pre-questionnaire results in areas such
      as residents enjoying the contact and activities. Impacting on ease-of use were
      technical difficulties. Although this study had limitations and could be improved
      by a better response rate and investigating the residents' acceptability of
      Betty, this study is one of the first to report that this novel technology may
      have much potential for engaging adults in RCFs.

PMID- 29198226
TI  - Environmental impacts of precision feeding programs applied in pig production.
AB  - This study was undertaken to evaluate the effect that switching from conventional
      to precision feeding systems during the growing-finishing phase would have on the
      potential environmental impact of Brazilian pig production. Standard life-cycle
      assessment procedures were used, with a cradle-to-farm gate boundary. The inputs
      and outputs of each interface of the life cycle (production of feed ingredients,
      processing in the feed industry, transportation and animal rearing) were
      organized in a model. Grain production was independently characterized in the
      Central-West and South regions of Brazil, whereas the pigs were raised in the
      South region. Three feeding programs were applied for growing-finishing pigs:
      conventional phase feeding by group (CON); precision daily feeding by group (PFG)
      (whole herd fed the same daily adjusted diet); and precision daily feeding by
      individual (PFI) (diets adjusted daily to match individual nutrient
      requirements). Raising pigs (1 t pig BW at farm gate) in South Brazil under the
      CON feeding program using grain cultivated in the same region led to emissions of
      1840 kg of CO2-eq, 13.1 kg of PO4-eq and 32.2 kg of SO2-eq. Simulations using
      grain from the Central-West region showed a greater climate change impact.
      Compared with the previous scenario, a 17% increase in climate change impact was
      found when simulating with soybeans produced in Central-West Brazil, whereas a
      28% increase was observed when simulating with corn and soybeans from Central
      West Brazil. Compared with the CON feeding program, the PFG and PFI programs
      reduced the potential environmental impact. Applying the PFG program mitigated
      the potential climate change impact and eutrophication by up to 4%, and
      acidification impact by up to 3% compared with the CON program. Making a further
      adjustment by feeding pigs according to their individual nutrient requirements
      mitigated the potential climate change impact by up to 6% and the potential
      eutrophication and acidification impact by up to 5% compared with the CON
      program. The greatest environmental gains associated with the adoption of
      precision feeding were observed when the diet combined soybeans from Central-West
      Brazil with corn produced in Southern Brazil. The results clearly show that
      precision feeding is an effective approach for improving the environmental
      sustainability of Brazilian pig production.

PMID- 29198227
TI  - Medical students' attitudes towards participating in a palliative medicine
      course: A new specialty in Israel.
AB  - BACKGROUND: Palliative medicine is a growing field in Israel, and its training
      program is still in process. The current study aimed to evaluate students'
      attitudes regarding a course in palliative care established in a division of
      oncology. METHOD: Some 45 medical students in their 5th to 6th years participated
      in a one-week course on palliative care. At the end of each training week,
      students were asked to complete a questionnaire, evaluating their attitudes
      regarding different aspects of the program content, such as its importance and
      relevance to their training as physicians, as well as the contribution of
      specific parts of the program to their knowledge regarding palliative care.
      RESULTS: The overall satisfaction of the 45 students was high. The most
      contributory parts of the course were the multidisciplinary team and the
      complementary and alternative medicine. Participating in the staff meetings and
      accompanying physicians in their daily work were scored as the least contributory
      parts.Significance of resultsThis preliminary study demonstrated students'
      overall high satisfaction with the newly established palliative care course and
      their need for more practical skills. Future studies should investigate and
      evaluate educational programs in palliative care in order to establish suitable
      training for medical students.

PMID- 29198228
TI  - Psychometric Properties of the Condom Use Barriers Scale for Adolescents.
AB  - Inconsistent condom use in young people is related to the perceived barriers to
      their use. The psychometric properties and factor structure of the new Condom Use
      Barriers Scale for Adolescents (CUBS-A) are analyzed. Concurrent validity was
      assessed by the Attitude towards condom use subscale of the validated HIV-AS test
      and the percentage of condom use variable. A total of 629 Spanish adolescents
      whose mean age was 15.17 (SD = 1.09; 51.5% boys) participated. Exploratory factor
      analysis supported a 15-item instrument with four factors: negotiation skills,
      perceived feelings, negative aspects of condoms, and disruption of the sexual
      experience, which explained 41.89% of the total variance (KMO = .84; chi2 =
      1071.93; p < .001). The results show high internal consistency (alpha = .86) and
      a good fit of the data to the model (NNFI = .93; CFI = .95; IFI = .95; RMSEA =
      .04). Its total score and most of its factors show acceptable correlation with
      the percentage of condom use, values that support the criterial validity (p <=
      .05). Gender differences were found in most subscales (p <= .001). The CUBS-A is
      a valid and reliable new instrument for assessing perceived barriers in
      adolescents for using condoms to protect themselves during sexual intercourse.

PMID- 29198229
TI  - Improvement of Self-regulated Learning in Mathematics through a Hypermedia
      Application: Differences based on Academic Performance and Previous Knowledge.
AB  - Self-regulation on behalf of the student is crucial in learning Mathematics
      through hypermedia applications and is an even greater challenge in these IT
      environments. Two aims are formulated. First, to analyze the effectiveness of a
      hypermedia tool in improving perceived knowledge of self-regulatory strategies
      and the perceived usage of the planning, executing and assessment strategy on
      behalf of students with low, medium and high levels of academic performance.
      Second, to analyze the effectiveness of the hypermedia tool in improving
      perceived usage of the strategy for planning, monitoring and evaluating on behalf
      of students with a perceived knowledge (low, medium and high). Participants were
      624 students (aged 10-13), classified into a treatment group (TG; 391) and a
      comparative group (CG; 233). They completed a questionnaire on perceived
      knowledge (Perceived Knowledge of Self-Regulatory Strategies) and another one on
      perceived usage of the strategy for planning, performing and evaluating
      (Inventory of Self-regulatory Learning Processes). Univariate covariance analyses
      (ANCOVAs) and Student-t tests were used. ANCOVA results were not statistically
      significant. However, the linear contrast indicated a significant improvement in
      perceived knowledge of strategies among the TG with low, medium and high academic
      performance (p <= .001). Results are discussed in the light of past and future
      research.

PMID- 29198230
TI  - A Reliability Generalization Meta-Analysis of the Padua Inventory of Obsessions
      and Compulsions.
AB  - The Padua Inventory (PI) of obsessions and compulsions is one of the most usually
      applied tests to assess obsessive-compulsive symptomatology in research contexts
      as well as for clinical and screening purposes. A reliability generalization meta
      analysis was accomplished to estimate the average reliability of the PI scores
      and to search for characteristics of the samples and studies that can explain the
      variability among reliability estimates. An exhaustive literature search enabled
      us to select 39 studies (53 independent samples) that reported alpha and/or test
      retest coefficients with the data at hand for the PI total score and subscales.
      An excellent average coefficient alpha was found for the PI total score (M =
      .935; 95%CI = .922-.949) and for Impaired Mental Control subscale (M = .911;
      95%CI = .897-.924), being good for Contamination (M = .861; 95%CI = .841-.882)
      and Checking (M = .880; 95%CI = .856-.903), and fair for Urges and Worries (M =
      .783; 95%CI = .745-.822). The average test-retest reliability for PI total score
      was also satisfactory (M = .835; 95%CI = .782-.877). Moderator analyses showed
      larger coefficients alpha for larger standard deviation of the PI total scores (p
      = .0005; R 2 = .46), for adapted versions of the test (p = .002; R 2 = .32), and
      for samples composed of clinical participants (p = .066; R 2 = .10). The
      practical implications of these results are discussed as well as the need for
      researchers to report reliability estimates with the data at hand.

PMID- 29198231
TI  - Effects of dietary calcium and phosphorus deficiency and subsequent recovery on
      broiler chicken growth performance and bone characteristics.
AB  - The ability of birds to modify dietary phosphorus utilisation when fed with low
      phosphorus and calcium (Ca) diets was studied using different sequences of
      dietary phosphorus and Ca restriction (depletion) and recovery (repletion) during
      the grower and the finisher phases. A total of 3600 Ross 708 broilers were
      randomly divided into 10 replicate pens per treatment (60 per pen, six pens per
      block). Chicks were fed a common starter diet from days 0 to 10, then a grower
      control diet (C: 0.90% Ca, 0.39% non-phytate phosphorus, nPP), mid-level diet (M:
      0.71% Ca, 0.35% nPP) or low Ca and nPP diet (L: 0.60% Ca, 0.30% nPP) from days 11
      to 21, followed by a finisher diet C, M or L containing, respectively, 0.85%,
      0.57% or 0.48% Ca and 0.35%, 0.29% or 0.24% nPP from days 22 to 37. Six treatment
      sequences were tested: CC, MM, LL, ML, LC and LM. Bone mineral content by dual
      energy X-ray, tibia ash, toe ash weight and tibia breaking strength were measured
      on days 21 and 37. No significant effect was observed on growth performance
      throughout the experiment. Diet L reduced bone mineral content, breaking
      strength, tibia and toe ash by 9%, 13%, 11% and 10%, respectively, on day 21
      (compared with diet C, for linear effect, P<0.05). On day 37, bone mineral
      content, breaking strength, tibia and toe ash remained lower compared with
      control values (CC v. MM v. LL, P<0.05 for linear and quadratic effects). Mineral
      depletion duration (ML v. LL) did not affect bone mineral status. Replenishing
      with the C diet during the finisher phase (LC) restored bone mineral content,
      tibia ash and toe ash weight better than the M diet did, but not to control
      levels (CC v. LC v. LM, for linear effect, P<0.05). These results confirm that
      dietary Ca and nPP may be reduced in the grower phase without affecting final
      growth performance or breaking strength as long as the finisher diet contains
      sufficient Ca and nPP. The practical applications of this strategy require
      further study in order to optimise the depletion and repletion steps.

PMID- 29198232
TI  - Adolescents' Daily Perception of Internalizing Emotional States by Means of
      Smartphone-based Ecological Momentary Assessment.
AB  - This study uses ecological momentary assessment (EMA) with smartphone devices to
      examine community adolescents' perceptions regarding both the intensity of and
      variability in their daily sadness/depression, anxiety, and somatic problems over
      the period of one week. Participants were 90 high-school students (M age = 14.61,
      SD = 1.64; range 12-18). The sample was divided according to gender (61.1%
      girls), migratory status (68.5% Spanish nationals and 31.5% Latin American
      immigrants), and level of psychological symptoms (17% risk group).
      Sadness/depression, anxiety, and somatic problems were examined using a
      smartphone app, five times per day, semi-randomly, for seven days (35 possible
      moments). A high proportion of adolescents did not report feelings of sadness
      (80.0%) or worry (79.3%) or physical symptoms on a daily basis (84.9%). Girls and
      the risk group reported greater intensity levels for the three analyzed problems
      than did boys and the normal group, respectively (p .05 in all cases). Day-to-day
      fluctuations in mood during the week were statistically significant but not
      meaningful (b = 0.0004, 95% CI [0.0001, 0.0008], p = .001).

PMID- 29198233
TI  - Subarachnoid haemorrhage from undiagnosed mycotic aortic aneurysm in a child.
AB  - We report a case of subarachnoid haemorrhage resulting from a mycotic aortic
      aneurysm in a child with CHD. The patient previously underwent operations for CHD
      and had a subarachnoid haemorrhage of unknown cause before the scheduled re
      operation. During the re-operation, a sealed rupture of an undiagnosed mycotic
      ascending aortic aneurysm was identified, and the causative organism was later
      identified as Streptococcus. A postoperative MRI indicated a partially thrombosed
      cerebral aneurysm. This case demonstrates that a mycotic aortic aneurysm can be a
      cause of intracranial haemorrhage in children.

PMID- 29198234
TI  - Cajal, Psychologist of Science.
AB  - This paper presents abundant empirical evidence to support the view that Santiago
      Ramon y Cajal was a pioneer of the emerging Psychology of Science discipline.
      Narrative analysis of his autobiography (Recollections of my Life) and some of
      his unspecialized works (Advice for a Young Investigator, The World from an
      Eighty-Year-Old's Point of View, and Cafe Chats) revealed that the Spanish
      histologist's interest in the psychology of scientists was part and parcel of a
      high-level, intellectual self-regulation strategy he applied on his path to
      success. This research led him to document various psychological conclusions
      about scientists in writing, so as to encourage, guide, and facilitate the work
      of junior researchers. Current knowledge of the Psychology of Science has
      confirmed many of the Nobel laureate's observations about psychosocial aspects of
      scientists, scientific reasoning, and creativity.

PMID- 29198235
TI  - Ultrasonographic measurements of localized fat accumulation in Shetland pony
      mares fed a normal v. a high energy diet for 2 years.
AB  - Health risks associated with obesity are more likely a factor of the localization
      of fat excess, rather than of elevated BW per se. The aim of this randomized
      controlled clinical trial was to determine the effect of a long-term high energy
      diet on BW, fat accumulation and localization. Eight Shetland pony mares, 3 to 7
      years old, were randomly divided into a control and a high energy (HE) diet group
      fed either maintenance or double maintenance energy requirements (200% net energy
      (NE)) for two consecutive summers, with a low energy diet in the winter in
      between. Body condition score (BCS) did not differ between the groups at the
      onset of the study (control 5.6+/-0.75 v. HE 6.3+/-0.5). From 12 weeks after
      starting the diet, ultrasonography of five different locations (retroperitoneal,
      axillary, withers, intercostal and rump) for adipose deposition, BCS and BW were
      measured monthly during the period that ponies received different diets.
      Statistical analysis was performed using a linear mixed-effects model with post
      hoc Bonferroni testing. P values <0.05 were considered significant. At week 12
      after the onset of the diet, fat thickness in the HE group was significantly
      greater than in the control group. During the monitoring period, the HE group
      showed a significant increase in mean (+/-SE) BW (+52%, 265+/-13.94kg) and BCS
      (+70%; to 9.0+/-0.4), while the control group was unchanged (BW 160+/-13.98 kg;
      BCS 3.8+/-0.4). At all locations, the fat depth in the HE group increased
      significantly, with the highest increase noted for retroperitoneal deposits. The
      conclusions were that a 200% NE diet induced subcutaneous and retroperitoneal fat
      accumulation, with the greatest increase in intra-abdominal deposits. The
      moderate increase of the subcutaneous fat depth followed by a plateau phase
      suggests the existence of a limit of adipose tissue expandability, as in man.

PMID- 29198236
TI  - Acetate alters the process of lipid metabolism in rabbits.
AB  - An experiment was conducted to investigate the effect of acetate treatment on
      lipid metabolism in rabbits. New Zealand Rabbits (30 days, n=80) randomly
      received a subcutaneous injection (2 ml/injection) of 0, 0.5, 1.0 or 2.0 g/kg per
      day body mass acetate (dissolved in saline) for 4 days. Our results showed that
      acetate induced a dose-dependent decrease in shoulder adipose (P0.05), acetate
      treatment significantly decreased the plasma adiponectin, insulin and
      triglyceride concentrations (P<0.05). In adipose, acetate injection significantly
      up-regulated the gene expression of peroxisome proliferator-activated receptor
      gamma (PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha),
      differentiation-dependent factor 1 (ADD1), adipocyte protein 2 (aP2), carnitine
      palmitoyltransferase 1 (CPT1), CPT2, hormone-sensitive lipase (HSL), G protein
      coupled receptor (GPR41), GPR43, adenosine monophosphate-activated protein kinase
      alpha1 (AMPKalpha1), adiponectin receptor (AdipoR1), AdipoR2 and leptin receptor.
      In addition, acetate treatment significantly increased the protein levels of
      phosphorylated AMPKalpha, extracellular signaling-regulated kinases 1 and 2
      (ERK1/2), p38 mitogen-activated protein kinase (P38 MAPK) and c-jun amino
      terminal kinase (JNK). In conclusion, acetate up-regulated the adipocyte-specific
      transcription factors (PPARgamma, C/EBPalpha, aP2 and ADD1), which were
      associated with the activated GPR41/43 and MAPKs signaling. Meanwhile, acetate
      decreased fat content via the upregulation of the steatolysis-related factors
      (HSL, CPT1 and CPT2), and AMPK signaling may be involved in the process.

PMID- 29198237
TI  - Risk correlates for physical-mental multimorbidities in South Africa: a cross
      sectional study.
AB  - AIMS: The aim of this study was to identify the risk correlates for coexisting
      common mental disorders (CMDs) in the chronic care population in South Africa,
      with the view to identifying particularly vulnerable patient populations.
      METHODS: The sample comprised 2549 chronic care patients enrolled in the baseline
      and endline rounds of a facility detection survey conducted by the Programme for
      Improving Mental Health Care in three large facilities in the Dr Kenneth Kaunda
      district in the North West province of South Africa. Participants were screened
      for depression using the Patient Health Questionnaire (PHQ9) and for alcohol
      misuse using the Alcohol Use Disorders Identification Test (AUDIT). Data were
      analysed according to the number of morbidities, disorder type (physical or
      mental) and demographic variables. Multimorbidity was defined as the presence of
      two or more disorders (physical and/or mental). RESULTS: Just over one-third of
      the sample reported two or more physical conditions. Women were more at risk of
      being depressed than were men, with men more at risk of alcohol misuse. Those who
      were employed were at lower risk of having coexisting CMDs, while being younger,
      HIV positive, and food deprived were all found to be associated with higher risk
      for having coexisting CMDs. CONCLUSION: In the face of the large treatment gap
      for CMDs in South Africa, and the role that coexisting CMDs can play in
      exacerbating the burden of chronic physical diseases, mental health screening and
      treatment interventions should target HIV-positive, younger patients living in
      circumstances where there is household food insecurity.

PMID- 29198238
TI  - The effect of adverse intrauterine conditions, early childhood growth and famine
      exposure on age at menopause: a systematic review.
AB  - When the follicle reserve, which is developed solely during the fetal period, is
      depleted, women enter menopause. Intrauterine and childhood adverse conditions
      might affect the ovarian capacity by influencing follicle production in the first
      trimester, limiting the initial follicle pool or mediate an accelerated
      follicular loss thereafter. To investigate if adverse early life influences
      result in younger age at menopause, the following online databases were
      systematically searched: PubMed, EMBASE, CINHAL (EBSCO) and Cochrane library
      (Wiley) up to 1 January 2017. Eligibility, data extraction and quality assessment
      was independently performed by two researchers. A total of 5278 studies were
      identified, 11 studies were deemed eligible and included. Nine were cohort
      studies, 1 case-control study and 1 twin study. Due to the diversity of reported
      data and risk estimates we were unable to pool data or perform meta-analysis on
      pooled data. Prenatal and childhood exposure to famine was significantly
      associated to an earlier age at menopause in three studies. Mean differences in
      age at menopause varied from 4 months up to 1.7 years between famine exposed and
      unexposed women. Three studies described a significant association between a low
      weight at ages 1 or 2 and a younger age at menopause. A younger age at menopause
      was associated with a higher weight at birth in only one study and with a high
      ponderal index, a measure for fatness at birth in another study. None of the nine
      studies reporting on low birth weight and age at natural menopause find a
      significant association.

PMID- 29198239
TI  - Medical Response to the Tianjin Explosions: Lessons Learned.
AB  - BACKGROUND: On August 12, 2015, a hazardous chemical explosion occurred in the
      Tianjin Port of China. The explosions resulted in 165 deaths, 8 missing people,
      injuries to thousands of people. We present the responses of emergency medical
      services and hospitals to the explosions and summarize the lessons that can be
      learned. METHODS: This study was a retrospective analysis of the responses of
      emergency medical services and hospitals to the Tianjin explosions. Data on
      injuries, outcomes, and patient flow were obtained from the government and the
      hospitals. RESULTS: A total of 46 ambulances and 143 prehospital care
      professionals were dispatched to the scene, and 198 wounded were transferred to
      hospitals by ambulance. More than 4000 wounded casualties surged into hospitals,
      and 798 wounded were admitted. Both emergency medical services and hospitals were
      quick and successful in the early stage of the explosions. The strategy of 4
      centralizations (4Cs) for medical services management in a mass casualty event
      was successfully applied. CONCLUSIONS: The risk of accidental events has
      increased in recent years. We should take advantage of the lessons learned from
      the explosions and apply these in future disasters. (Disaster Med Public Health
      Preparedness. 2018; 12: 411-414).

PMID- 29198240
TI  - Aligning the ICD-11 classification of disorders due to substance use with global
      service needs.
AB  - The use of psychoactive, potentially dependence-producing substances is highly
      prevalent around the world, and contributes substantially to global disease
      burden. There is a major gap between the need for treatment for substance use
      disorders. Changes proposed for the classification of substance use disorders in
      the Eleventh Revision of the International Classification of Diseases and Related
      Health Problems, based on a public health approach, have important implications
      for the conceptualisation, structure and availability of services. These include:
      (1) an updated and expanded range of substance classes; (2) greater specification
      of different harmful patterns of substance use, which may be continuous or
      episodic and recurrent; (3) a new category to denote single episodes of harmful
      use; (4) a category describing hazardous use of substances; and (5)
      simplification of diagnostic guidelines for substance dependence. This paper
      describes these changes and the opportunities they present for improved
      prevention, treatment, monitoring and health policy.

PMID- 29198241
TI  - A parallel universe where psychiatry is like the rest of medicine.

PMID- 29198242
TI  - Effect of oral progesterone and caffeine at the end of gestation on farrowing
      duration and piglet growth and survival.
AB  - The profitability of pig production is constrained by high incidences of peri
      parturient and pre-weaning piglet mortality. Supplementing sows with either
      progesterone or caffeine during the last week of gestation can reduce stillbirths
      and improve piglet performance. However, the consequences of combining these two
      substances has not been investigated. The aim of the current study was to
      determine the effect of oral supplementation of sows with progesterone (regumate)
      and caffeine at the end of gestation on the timing and progression of farrowing,
      as well as piglet survival and growth to weaning. From days 111 to 113 of
      gestation, 20 Large White pregnant sows (parity 3.0+/-0.45) received 5 ml of
      Regumate Porcine (0.4 w/v oral solution; MSD Animal Health) daily on top of their
      morning ration. Sows were stratified according to parity and predicted farrowing
      date, and allocated at random to receive a diet supplemented with either 0 g
      caffeine/kg diet (CONT) or 2.4 g of caffeine/kg diet (CAFF) from day 113 of
      gestation until parturition (n=10 sows/treatment). Treatment did not affect total
      litter size; however, CONT sows gave birth to more live and fewer dead piglets
      compared with CAFF sows; 14.5+/-0.73 v. 11.7+/-1.03 and 0.7+/-0.20 v. 3.2+/-0.77;
      P<0.05). Mean, minimum and maximum piglet birthweight were unaffected by
      treatment. Compared with the control, caffeine increased the proportion of
      piglets with a birthweight <1 kg (0.16+/-0.05 v. 0.05+/-0.02; P=0.072) and
      decreased the proportion of live born piglets surviving to day 5 postpartum
      (0.77+/-0.06 v. 0.90+/-0.02; P<0.05) and to weaning (0.74+/-0.06 v. 0.90+/-0.02;
      P<0.05). Overall, the current data provided the first evidence that caffeine
      supplementation of sows receiving progesterone to prevent premature farrowing
      impaired piglet survival during, and shortly after parturition. This negative
      outcome may be linked to extended farrowing durations and an increase in the
      proportion of very light piglets at birth. These data provide compelling, albeit
      preliminary, evidence that caffeine and progesterone should not be used together
      at the end of gestation.

PMID- 29198243
TI  - Maternal grazing on stubble and Mediterranean shrubland improves meat lipid
      profile in light lambs fed on concentrates.
AB  - Concentrates-fed lamb meat is often associated with an unfavourable lipid profile
      (high levels of saturated and/or n-6 polyunsaturated fatty acids; SFA and PUFA).
      For this reason, Spanish sheep producers from Mediterranean areas are turning to
      traditional grazing by ewes to obtain healthier lamb meat. The objective of this
      research was to determine the effects of maternal grazing on the fatty acid (FA)
      composition of weaned lamb meat. The ewes (Segurena breed) were allocated to two
      different rearing systems during pregnancy (5 months) and lactation (45 days):
      (i) feeding indoors on barley grain and lucerne pellets; (ii) grazing on cereal
      stubble, fallow land and seasonal pastures consisting of Mediterranean shrubs,
      herbs and trees. Two groups of 20 autumn and spring lambs were sampled. The lambs
      were weaned at 13.1+/-0.9 kg and 45.0+/-4.1 days age and fed on grain-based
      concentrates until they reached 24.8+/-2.1 kg live weight (light lambs
      slaughtered at 98.3+/-3.6 days of age). The FA content was determined in the
      intramuscular loin fat by gas chromatography using a flame ionization detector.
      The ewe diet did not affect the levels of the main lamb FAs (C18:1c+t, C16:0 and
      C18:2c), and so did not provide any additional reduction in fat saturation.
      Saturated fatty acids represented around 40% of total FAs determined in the meat.
      Ewe grazing acted as an n-3 PUFA-promoting diet, providing a lamb meat with a
      lower n-6/n-3 ratio. Spring lamb meat had higher proportions of n-3 PUFA (C18:3n
      3, C20:5, C22:5 and C22:6) and conjugated linoleic acid (C18:2c9t11+c11t9) to the
      detriment of the n-6 PUFAs (C20:4, C20:2 and C22:4), while autumn lamb meat also
      had higher levels of C18:3n-3 and C18:3n-6, and lower level of C20:4, which
      points to little seasonal differences. The n-6/n-3 ratio achieved by ewe grazing
      fell from 8.2 to 4.1 (Spring) and from 7.6 to 5.5 (Autumn), values which are
      close to those recommended in human diet for good cardiovascular health. These n
      6/n-3 reductions were associated with lower levels of total PUFA and C20:4n-6.
      Our research concluded that grazing on stubble and Mediterranean shrubland by
      ewes, a sustainable rearing practice involving local agro resources, contributed
      to obtaining weaned lamb meat with a more favourable lipid profile and so can be
      recommended to sheep farmers.

PMID- 29198245
TI  - Monophyly of the species of Hepatozoon (Adeleorina: Hepatozoidae) parasitizing
      (African) anurans, with the description of three new species from hyperoliid
      frogs in South Africa.
AB  - Haemogregarines (Apicomplexa: Adeleiorina) are a diverse group of haemoparasites
      reported from almost all vertebrate classes. The most commonly recorded
      haemogregarines to parasitize anurans are species of Hepatozoon Miller, 1908. To
      date 16 Hepatozoon species have been described from anurans in Africa, with only
      a single species, Hepatozoon hyperolli (Hoare, 1932), infecting a member of the
      Hyperoliidae. Furthermore, only two Hepatozoon species are known from South
      African anurans, namely Hepatozoon theileri (Laveran, 1905) and Hepatozoon ixoxo
      Netherlands, Cook and Smit, 2014, from Amietia delalandii (syn. Amietia
      quecketti) and three Sclerophrys species, respectively. Blood samples were
      collected from a total of 225 individuals representing nine hyperoliid species
      from several localities throughout northern KwaZulu-Natal, South Africa. Twenty
      frogs from three species were found positive for haemogregarines, namely
      Afrixalus fornasinii (6/14), Hyperolius argus (2/39), and Hyperolius marmoratus
      (12/74). Based on morphological characteristics, morphometrics and molecular
      findings three new haemogregarine species, Hepatozoon involucrum Netherlands,
      Cook and Smit n. sp., Hepatozoon tenuis Netherlands, Cook and Smit n. sp. and
      Hepatozoon thori Netherlands, Cook and Smit n. sp., are described from hyperoliid
      hosts. Furthermore, molecular analyses show anuran Hepatozoon species to be a
      separate monophyletic group, with species isolated from African hosts forming a
      monophyletic clade within this cluster.

PMID- 29198246
TI  - Neurocognitive dysfunctioning and the impact of comorbid depression and anxiety
      in patients with somatic symptom and related disorders: a cross-sectional
      clinical study.
AB  - BACKGROUND: The prevalence and severity of neurocognitive dysfunctioning of
      patients with somatic symptom and related disorders (SSRD) is unknown.
      Furthermore, the influence of comorbid depression and anxiety has not been
      evaluated. This study examines neurocognitive dysfunctioning of patients with
      SSRD and explores if comorbid depression and anxiety is associated with specific
      neurocognitive dysfunctioning. METHODS: Cross-sectional study with consecutive
      patients suffering from SSRD visiting an outpatient specialty mental health care
      Centre of Excellence for SSRD. Extensive neuropsychological assessment and
      assessment of depression and anxiety symptom levels using the Patient-Health
      Questionnaire-9 and General Anxiety Disorder questionnaire-7 were performed at
      intake. Multivariate analysis was performed. RESULTS: The study sample consisted
      of 201 SSRD patients, with a mean age of 43 years (Standard deviation = 13)
      years; 37.8% were male. Neurocognitive dysfunction in the domains information
      processing speed, sustained and divided attention, working memory, verbal and
      visual memory were reported, compared with normative data. Comorbid depression
      and anxiety occurred frequently within the sample (75.1% and 65.7%,
      respectively). Neurocognitive dysfunctioning was worse in patients suffering from
      comorbid depression [multivariate F (7,161) = 2.839, p = 0.008] but not in
      patients with comorbid anxiety. CONCLUSIONS: Poor neurocognitive performance of
      patients with SSRD is common and worsens in case of comorbid depression. This may
      explain treatment dropout of patients with SSRD from neurocognitive behavioral
      therapy. Research on novel interventions is needed targeting neurocognitive
      functioning of patients with SSRD, particularly those with comorbid depression.

PMID- 29198244
TI  - Depressive and anxiety symptoms and cortical amyloid deposition among cognitively
      normal elderly persons: the Mayo Clinic Study of Aging.
AB  - BACKGROUND: Little is known about the association of cortical Abeta with
      depression and anxiety among cognitively normal (CN) elderly persons. METHODS: We
      conducted a cross-sectional study derived from the population-based Mayo Clinic
      Study of Aging in Olmsted County, Minnesota; involving CN persons aged >= 60
      years that underwent PiB-PET scans and completed Beck Depression Inventory-II
      (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an
      expert consensus panel. Participants were classified as having abnormal (>=1.4;
      PiB+) or normal PiB-PET (<1.4; PiB-) using a global cortical to cerebellar ratio.
      Multi-variable logistic regression analyses were performed to calculate odds
      ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and
      sex. RESULTS: Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one
      point symptom increase in the BDI (OR = 1.03; 1.00-1.06) and BAI (OR = 1.04; 1.01
      1.08) was associated with increased odds of PiB-PET+. The number of participants
      with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET-
      group but the difference was not significant (OR = 1.42; 0.83-2.43). Similarly,
      the number of participants with BAI > 10 (clinical anxiety) was greater in the
      PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.77;
      0.97-3.22). CONCLUSIONS: As expected, depression and anxiety levels were low in
      this community-dwelling sample, which likely reduced our statistical power.
      However, we observed an informative albeit weak association between increased BDI
      and BAI scores and elevated cortical amyloid deposition. This observation needs
      to be tested in a longitudinal cohort study.

PMID- 29198247
TI  - Analysis of Pseudohomophone Orthographic Errors through Functional Magnetic
      Resonance Imaging (fMRI).
AB  - The study of orthographic errors in a transparent language such as Spanish is an
      important topic in relation to writing acquisition because in Spanish it is
      common to write pseudohomophones as valid words. The main objective of the
      present study was to explore the possible differences in activation patterns in
      brain areas while processing pseudohomophone orthographic errors between
      participants with high (High Spelling Skills (HSS)) and low (Low Spelling Skills
      (LSS)) spelling orthographic abilities. We hypothesize that (a) the detection of
      orthographic errors will activate bilateral inferior frontal gyri, and that (b)
      this effect will be greater in the HSS group. Two groups of 12 Mexican
      participants, each matched by age, were formed based on their results in a group
      of spelling-related ad hoc tests: HSS and LSS groups. During the fMRI session,
      two experimental tasks were applied involving correct and pseudohomophone
      substitution of Spanish words. First, a spelling recognition task and second a
      letter searching task. The LSS group showed, as expected, a lower number of
      correct responses (F(1, 21) = 52.72, p <.001, eta2 = .715) and higher reaction
      times compared to the HSS group for the spelling task (F(1, 21) = 60.03, p <.001,
      eta2 = .741). However, this pattern was reversed when the participants were asked
      to decide on the presence of a vowel in the words, regardless of spelling. The
      fMRI data showed an engagement of the right inferior frontal gyrus in HSS group
      during the spelling task. However, temporal, frontal, and subcortical brain
      regions of the LSS group were activated during the same task.

PMID- 29198248
TI  - Effects of dark brooders and overhangs on free-range use and behaviour of slow
      growing broilers.
AB  - Broiler chickens often make limited use of the free-range area. Range use is
      influenced by type of shelter available. Range use may possibly be improved by a
      more gradual transition from the house to the range and by using dark brooders
      (secluded warm, dark areas in the home pen) that mimic aspects of a broody hen
      and possibly reduce fearfulness. The aim of this study was to assess effects of
      dark brooders on fearfulness, free-range use and behaviour later in life. Another
      aim was to test the chickens' preference for shelter type and the effects of
      overhangs outside of the pop holes to provide a gradual transition to the range.
      Three production rounds, each with 440 Sasso broiler chickens (110/group), were
      completed. Chicks were housed indoors from days 0 to 25; per round, two groups
      had access to a dark brooder, whereas the other two groups had conventional IR
      lamps. Fearfulness was assessed by the open field (OF) and tonic immobility (TI)
      tests on days 22 to 24 on 25 chicks/group per round. Birds were then moved to
      four mobile houses from which they could access both grassland with artificial
      shelter (AS) and short rotation coppice (SRC). Two of the houses had overhangs
      extending from the pop holes; these were switched between the four houses weekly.
      Free-range use and behaviour were observed three times daily from Monday to
      Friday. Dark brooders did not affect results from the OF or TI test, except for
      jumps in the OF test which tended to occur less often in brooded chicks. Neither
      dark brooders (34.9% without v. 31.7% with brooder) nor overhangs (32.5% without
      v. 34.1% with overhangs) influenced the percentage of chickens outside. Chickens
      showed a clear preference for SRC, range use increased over time in SRC, and more
      birds ranged farther from the house in SRC. Behaviours of chickens observed
      outside were mainly influenced by shelter type, age of the birds and distance
      from the house. Locomotion tended to occur more in the presence of overhangs.
      Overall, these results could not confirm the hypothesis that dark brooders would
      decrease fearfulness and thereby increase free-range use. Overhangs also did not
      improve free-range use, and neither brooders nor overhangs had considerable
      impact on behaviour of chickens outside. Chickens clearly preferred dense natural
      vegetation over AS and ranged farther in it, indicating that this type of shelter
      is more suitable for slow-growing free-range broilers.

PMID- 29198249
TI  - The Closing-In Phenomenon in an Ecological Walking Task.
AB  - OBJECTIVES: Alzheimer's disease (AD) patients may show the Closing-in (CI), a
      tendency to reproduce figures close to or superimposed on the model. AD patients
      with CI might manifest reduced functional independence compared to AD patients
      without CI, but no study directly assessed if CI can hamper common daily living
      activities. To address this issue here we investigated whether AD patients with
      CI veer their walking trajectory toward irrelevant objects more often than AD
      patients without CI. METHODS: Fifty AD individuals, and 20 age- and education
      matched healthy adults, underwent a graphic copying task to detect CI and a newly
      developed walking task to assess the tendency to veer toward irrelevant objects
      and to bump into them. All participants also completed a comprehensive
      neuropsychological battery to assess dementia severity; impairments in
      frontal/executive, visuo-spatial, visuo-constructional, and memory domains; and
      functional independence in daily living activities. RESULTS: Graphic CI occurred
      in 34/50 (68%) AD patients (AD-CI group) who achieved significantly lower scores
      on frontal/executive abilities, and daily living functioning than AD individuals
      not showing CI. Most AD-CI patients (20/34; 58.8%) also showed at least one
      veering error in the walking task. Participants with CI and veering errors showed
      significantly poorer performance on Stroop test, and lower level of functional
      independence than AD individuals with CI in isolation. CONCLUSIONS: CI on graphic
      tasks can identify difficulties in walking and in complying with everyday
      activities in AD patients. These observations demonstrate the value of assessing
      CI in copying tasks. (JINS, 2018, 24, 437-444).

PMID- 29198250
TI  - Cornicle secretions by Aphis fabae (Hemiptera: Aphididae) result in age-dependent
      costs and improved host suitability for Lysiphlebus fabarum (Marshall)
      (Hymenoptera: Braconidae).
AB  - We examined the life history consequences of cornicle secretion by Aphis fabae
      Scopoli in second and fourth instars, and its effects on host suitability for its
      parasitoid, Lysiphlebus fabarum (Marshall). Cornicle secretion did not affect
      aphid fecundity, but secretion in the second instar enhanced life table
      parameters, whereas secretion in the fourth instar affected them negatively,
      suggesting a higher cost of secretion in later instars. Secretion in either
      instar improved host suitability for L. fabarum. Although control and treated
      aphids were parasitized at similar rates, and with similar success, wasps
      developed faster and emerged as larger adults in aphids that had secreted,
      regardless of instar. Transgenerational effects were also evident. Progeny
      emergence was higher when parental wasps developed in fourth instars than in
      seconds, whether aphids secreted or not, and progeny were larger when parental
      hosts secreted in the second instar, but not in the fourth. Secreting fourth
      instars were preferred to controls by L. fabarum females in choice tests, but not
      secreting second instars, and fourth-instar secretion improved wasp emergence.
      When control aphids were attacked, second instars were more likely to secrete
      than fourth instars, whereas the latter were more likely to kick the parasitoid.
      Cornicle secretion reduced the probability of subsequent secretion events and the
      frequency of other aphid defensive behaviors, indicating energetic tradeoffs
      among defensive tactics. Overall, our results revealed that cornicle secretion by
      immature A. fabae exacts both physiological and behavioral costs and results in
      improved host suitability for its parasitoid.

PMID- 29198251
TI  - The Empathic Process and Misconceptions that Lead to Burnout in Healthcare
      Professionals.
AB  - Empathy has been identified as a relevant variable in order to predict burnout in
      healthcare professionals. In addition, assertiveness and self-esteem have been
      considered relevant variables to develop empathic capacity. In the other hand,
      misconceptions surrounding empathy constitute a risk factor for burnout. Two
      adult samples (N = 252 and N = 275) were used to explore and confirm the
      underlying structure of two questionnaires. The Exercise of Process of Empathy
      (EPE) scale (18 items) confirmatory factor analysis including 5 dimensions
      (cognitive and emotional comprehension, attention, clarity and assertiveness),
      showed reasonable goodness- of-fit indices chi2(130) = 269.63, p < .001; RMSEA =
      .069 90% CI [0.058 - 0.079]; CFI = .965; TLI = .959. Alpha coefficient resulted
      .848. Common Misconceptions (EH) of empathy scale (16 items) confirmatory factor
      analysis, including 3 dimensions (feeling, confluence and character
      misconceptions) also obtained reasonable goodness-of-fit indices chi 2 (101) =
      250.59, p < .001; RMSEA = .075 90% CI [0.063 - 0.087]; CFI = .952; TLI = .943.
      Alpha coefficient for Character resulted .727 (5 items), for Confluence .764 (5
      items) and for Feeling .822 (6 items). The SEM model's R 2 resulted .303, being
      EH (misconceptions) a risk factor (b* = .171), EPE (empathy process) a protection
      factor (b* = -.183). The model partially explains how misconceptions empathy
      process and self-esteem (b* = -.334) relate to burnout syndrome in healthcare
      professionals; what is more, it heralds a potential means to prevent it.

PMID- 29198253
TI  - Resolution of severe psychogenic dysphagia with ECT in an elderly patient.
AB  - ABSTRACTIn this report we describe an 82-year female with a longstanding anxiety
      disorder who developed severe psychogenic dysphagia, leading to hospitalization
      due to failure to thrive. We describe for the first time the use of
      electroconvulsive therapy (ECT) to successfully manage a patient with
      pharmacological treatment resistant psychogenic dysphagia.

PMID- 29198252
TI  - Prevalence and correlates of subjective memory complaints in Vietnamese adults.
AB  - : ABSTRACTBackground:Low- and middle-income countries such as Vietnam are home to
      a majority of the world's population with dementia, yet little is known regarding
      how individuals in these countries perceive memory problems that might be
      indicative of cognitive impairment. This study examined the prevalence and
      correlates of subjective memory complaints (SMCs) in Vietnamese adults in Da
      Nang, Vietnam. METHODS: A stratified sample of 600 adults (aged >= 55 years)
      living in Da Nang, Vietnam, and surrounding areas were recruited to participate
      in a cross-sectional study. Students and faculty from the National Technical
      Medical College Number 2 administered questionnaires in participants' homes
      regarding socio-demographic characteristics, functional health, social support,
      cognitive and mental health, and SMCs. Descriptive and stepwise regression
      analyses examined the prevalence and correlates of SMCs. RESULTS: Approximately
      64% of the sample reported at least poor memory and 39% said that memory
      interfered with their daily life at least somewhat. Multivariate regression
      analyses (adjusted for all covariates) showed that depressive symptoms, cognitive
      impairment, self-rated health and pain, and material hardship were associated
      with SMCs. CONCLUSIONS: Prevalence of SMCs as well as depressive symptoms was
      high in this Vietnamese population. Although future research using more detailed
      measures of subjective memory and which include longitudinal data are required,
      the need for physicians to routinely assess Vietnamese patients for depression,
      SMCs, and cognitive impairment may be warranted.

PMID- 29198254
TI  - Predisposing, enabling, and need factors of service utilization in the elderly
      with mental health problems.
AB  - : ABSTRACTBackground:Empirical data on the use of services due to mental health
      problems in older adults in Europe is lacking. The objective of this study is to
      identify factors associated with service utilization in the elderly. METHODS: As
      part of the MentDis_ICF65+ study, N = 3,142 people aged 65-84 living in the
      community in six European and associated countries were interviewed. Based on
      Andersen's behavioral model predisposing, enabling, and need factors were
      analyzed with logistic regression analyses. RESULTS: Overall, 7% of elderly and
      11% of those with a mental disorder had used a service due to mental health
      problems in the last 12 months. Factors significantly associated with underuse
      were male sex, lower education, living in the London catchment area, higher
      functional impairment and more comorbid mental disorders. The most frequently
      reported barrier to service use was personal beliefs, e.g. "I can deal with my
      problem on my own" (90%). CONCLUSION: Underutilization of mental health services
      among older people in the European community is common and interventions are
      needed to achieve an adequate use of services.

PMID- 29198255
TI  - Pediatric Cardiac Intensive Care Society Statement: caring for children with
      critical cardiac disease across the globe.

PMID- 29198256
TI  - The global burden of paediatric heart disease.
AB  - An estimated 15 million children die or are crippled annually by treatable or
      preventable heart disease in low- and middle-income countries. Global efforts to
      reduce under-5 mortality have focused on reducing death from communicable
      diseases in low- and middle-income countries with little to no attention focusing
      on paediatric CHD and acquired heart disease. Lack of awareness of CHD and
      acquired heart disease, access to care, poor healthcare infrastructure, competing
      health priorities, and a critical shortage of specialists are important reasons
      why paediatric heart disease has not been addressed in low resourced settings.
      Non-governmental organisations have taken the lead to address these challenges.
      This review describes the global burden of paediatric heart disease and
      strategies to improve the quality of care for paediatric heart disease. These
      strategies would improve outcomes for children with heart disease.

PMID- 29198257
TI  - Global perspective on training and staffing for paediatric cardiac critical care.
AB  - This manuscript provides a global perspective on physician and nursing education
      and training in paediatric cardiac critical care, including available resources
      and delivery of care models with representatives from several regions of the
      world including Africa, Israel, Asia, Australasia, Europe, South America, and the
      United States of America.

PMID- 29198258
TI  - Perioperative infections in congenital heart disease.
AB  - BACKGROUND: Perioperative infections have significant consequences for children
      with congenital heart disease (CHD), which can manifest as acute or chronic
      infection followed by poor growth and progressive cardiac failure. The
      consequences include delayed or higher-risk surgery, and increased postoperative
      morbidity and mortality. METHODS: A systematic search for studies evaluating the
      burden and interventions to reduce perioperative infections in children with CHD
      was undertaken using PubMed. RESULTS: Limited studies conducted in low- to middle
      income countries demonstrated the large burden of perioperative infections among
      children with CHD. Most studies focussed on infections after surgery. Few studies
      evaluated strategies to prevent preoperative infection or the impact of infection
      on decision-making around the timing of surgery. Children with CHD have multiple
      risk factors for infections including delayed presentation, inadequate treatment
      of cardiac failure, and poor nutrition. CONCLUSIONS: The burden of perioperative
      infections is high among children with CHD, and studies evaluating the
      effectiveness of interventions to reduce these infections are lacking. As good
      nutrition, early corrective surgery, and measures to reduce nosocomial infection
      are likely to play a role, practical steps can be taken to make surgery safer.

PMID- 29198259
TI  - Management of undernutrition and failure to thrive in children with congenital
      heart disease in low- and middle-income countries.
AB  - Poor growth with underweight for age, decreased length/height for age, and
      underweight-for-height are all relatively common in children with CHD. The
      underlying causes of this failure to thrive may be multifactorial, including
      innate growth potential, severity of cardiac disease, increased energy
      requirements, decreased nutritional intake, malabsorption, and poor utilisation
      of absorbed nutrition. These factors are particularly common and severe in low-
      and middle-income countries. Although nutrition should be carefully assessed in
      all patients, failure of growth is not a contraindication to surgical repair, and
      patients should receive surgical repair where indicated as soon as possible.
      Close attention should be paid to nutritional support - primarily enteral
      feeding, with particular use of breast milk in infancy - in the perioperative
      period and in the paediatric ICU. This nutritional support requires specific
      attention and allocation of resources, including appropriately skilled personnel.
      Thereafter, it is essential to monitor growth and development and to identify
      causes for failure to catch-up or grow appropriately.

PMID- 29198260
TI  - Management of late presentation congenital heart disease.
AB  - In many parts of the world, mostly low- and middle-income countries, timely
      diagnosis and repair of congenital heart diseases (CHDs) is not feasible for a
      variety of reasons. In these regions, economic growth has enabled the development
      of cardiac units that manage patients with CHD presenting later than would be
      ideal, often after the window for early stabilisation - transposition of the
      great arteries, coarctation of the aorta - or for lower-risk surgery in infancy -
      left-to-right shunts or cyanotic conditions. As a result, patients may have
      suffered organ dysfunction, manifest signs of pulmonary vascular disease, or the
      sequelae of profound cyanosis and polycythaemia. Late presentation poses unique
      clinical and ethical challenges in decision making regarding operability or
      surgical candidacy, surgical strategy, and perioperative intensive care
      management.

PMID- 29198261
TI  - Inter-hospital transport of the child with critical cardiac disease.
AB  - Centralisation of services such as cardiology, cardiac surgery, and intensive
      care in many parts of the world has resulted in the need to safely transport
      children with critical cardiac disease from local hospitals to specialist centres
      for diagnostic, surgical, and/or critical care intervention. The transport of
      this cohort of children, whether locally or internationally, can present specific
      clinical and logistical challenges. An international group of clinicians with
      expertise in cardiac care and critical care transport worked together to
      summarise current clinical practice relating to key areas of transport. This
      expert review covers the transport of the child with critical cardiac disease in
      terms of referral triage and advice, enabling optimal management of locally
      available resources, clinical stabilisation before transport, international air
      transport, transport considerations in low- and middle-income countries, and the
      transport of children with specific cardiac conditions. As specialist services
      are centralised to fewer large centres, the need for safe and timely inter
      hospital transport of children with critical cardiac disease is only expected to
      rise in the future. The key principles outlined in this review will be helpful
      for practitioners in global settings who are, or might be, involved in
      transporting children between hospitals.

PMID- 29198262
TI  - Medical missions for the provision of paediatric cardiac surgery in low- and
      middle-income countries.
AB  - This review will outline the role of visiting cardiac surgical teams in low- and
      middle-income countries drawing on the collective experience of the authors in a
      wide range of locations. Requests for assistance can emerge from local programmes
      at a beginner or advanced stage. However, in all circumstances, careful pre-trip
      planning is necessary in conjunction with clinical and non-clinical local
      partners. The clinical evaluation, surgical procedures, and postoperative care
      all serve as a template for collaboration and education between the visiting and
      local teams in every aspect of care. Education focusses on both common and
      patient-specific issues. Case selection must appropriately balance the clinical
      priorities, safety, and educational objectives within the time constraints of
      trip duration. Considerable communication and practical challenges will present,
      and clinicians may need to make significant adjustments to their usual practice
      in order to function effectively in a resource-limited, unfamiliar, and
      multilingual environment. The effectiveness of visiting trips should be measured
      and constantly evaluated. Local and visiting teams should use data-driven
      evaluations of measurable outcomes and critical qualitative evaluation to
      repeatedly re-assess their interim goals. Progress invariably takes several years
      to achieve the final goal: an autonomous self-governing, self-financed, cardiac
      programme capable of providing care for children with complex CHD. This outcome
      is consistent with redundancy for the visiting trips model at the site, although
      fraternal, professional, and academic links will invariably remain for many
      years.

PMID- 29198263
TI  - Partnership models for the establishment of sustainable paediatric cardiac
      surgical and cardiac intensive care programmes in low- and middle-income
      countries.
AB  - The care of patients with CHD remains a challenge in low- and middle-income
      countries. Their health systems have not been able to achieve consistently high
      performance in this field. The large volume of patients, manpower constraints,
      inconsistencies in the level and type of background training of the teams caring
      for this patient population, and the inadequate quality control systems are some
      of the barriers to achieving excellence of care. We describe three different
      international projects supporting the paediatric cardiac surgical and paediatric
      cardiac intensive care programmes in Latin America, Asia, and the Caribbean.

PMID- 29198265
TI  - Review: Feed demand landscape and implications of food-not feed strategy for food
      security and climate change.
AB  - The food-feed competition is one of the complex challenges, and so are the
      ongoing climate change, land degradation and water shortage for realizing
      sustainable food production systems. By 2050 the global demand for animal
      products is projected to increase by 60% to 70%, and developing countries will
      have a lion's share in this increase. Currently, ~800 million tonnes of cereals
      (one-third of total cereal production) are used in animal feed and by 2050 it is
      projected to be over 1.1 billion tonnes. Most of the increase in feed demand will
      be in developing countries, which already face many food security challenges.
      Additional feed required for the projected increased demand of animal products,
      if met through food grains, will further exacerbate the food insecurity in these
      countries. Furthermore, globally, the production, processing and transport of
      feed account for 45% of the greenhouse gas emissions from the livestock sector.
      This paper presents approaches for addressing these challenges in quest for
      making livestock sector more sustainable. The use of novel human-inedible feed
      resources such as insect meals, leaf meals, protein isolates, single cell protein
      produced using waste streams, protein hydrolysates, spineless cactus, algae, co
      products of the biofuel industry, food wastes among others, has enormous
      prospects. Efficient use of grasslands also offers possibilities for increasing
      carbon sequestration, land reclamation and livestock productivity. Opportunities
      also exist for decreasing feed wastages by simple and well proven practices such
      as use of appropriate troughs, increase in efficiency of harvesting crop residues
      and their conversion to complete feeds especially in the form of densified feed
      blocks or pellets, feeding as per the nutrient requirements, among others.
      Available evidence have been presented to substantiate arguments that: (a) for
      successful and sustained adoption of a feed technology, participation of the
      private sector and a sound business plan are required, (b) for sustainability of
      the livestock production systems, it is also important to consider the
      consumption of animal products and a case has been presented to assess future
      needs of animal source foods based on their requirements for healthy living,

PMID- 29198264
TI  - International quality improvement initiatives.
AB  - Across the globe, the implementation of quality improvement science and
      collaborative learning has positively affected the care and outcomes for children
      born with CHD. These efforts have advanced the collective expertise and
      performance of inter-professional healthcare teams. In this review, we highlight
      selected quality improvement initiatives and strategies impacting the field of
      cardiovascular care and describe implications for future practice and research.
      The continued leveraging of technology, commitment to data transparency, focus on
      team-based practice, and recognition of cultural norms and preferences ensure the
      success of sustainable models of global collaboration.

PMID- 29198266
TI  - Influence of batch-specific biochemical egg characteristics on embryogenesis and
      hatching success in farmed pikeperch.
AB  - Low and variable egg quality remains a major issue in aquaculture impeding a
      reliable and continuous supply of larvae, particularly in emerging species, such
      as pikeperch, Sander lucioperca. We assessed the influence of batch-specific egg
      parameters (fatty acid (FA) profiles, cortisol content) on embryo life-stages
      until hatching (survival at 2, 24, 48, 72 h post fertilization (hpf), hatching
      rate) in an integrated study under commercial hatchery conditions (44 egg
      batches). Embryo mortality was elevated until 48 hpf (average 9.8% mortality
      between 2 and 48 hpf). Embryos surviving until 48 hpf were very likely (98.5%) to
      hatch successfully. The inherent egg FA composition was variable in-between
      batches. Total FA content ranged form 66.1 to 171.7 ug/mg (dry matter) total FA.
      Whereas specific FA ,18 : 0 and 20 : 5(n-3) (eicosapentaenoic acid) of the polar
      fraction and the ratio of 22 : 6(n-3) (docosahexaenoic acid) to 20 : 5(n-3)
      within the neutral fraction, were significantly correlated with early embryo
      development, contents of the respective FA did not differ between high (>90%
      hatching rate), mid (70% to 90% hatching rate) and low (<70% hatching rate)
      quality egg batches. Late embryo development and hatching were relatively
      independent of the FA profiles highlighting stage-dependent influences especially
      during early embryogenesis. Cortisol levels ranged from 22.7 to 293.2 ng/ml and
      did not directly explain for mortalities. However, high cortisol was associated
      with a lower content of specific FA, in particular highly unsaturated FA. These
      results demonstrate the magnitude of inter-individual differences in the batch
      specific biochemical egg composition under stable hatchery conditions and suggest
      a stress-mediated lack of essential FA, which in turn affects early embryo
      survival. Surprisingly, embryos are able to cope well with a broad range of
      inherent egg parameters, which limits their predictive potential for egg quality
      in general. Still, specific FA profiles of high quality egg batches have
      potential for formulating species-specific broodstock diets and improving
      reproductive management in pikeperch.

PMID- 29198267
TI  - RAS-related protein 1: an estrogen-responsive gene involved in development and
      molting-mediated regeneration of the female reproductive tract in chickens.
AB  - It is important to identify molecular candidates involved in morphological and
      functional changes in the female reproductive system. We have discovered several
      candidate genes that were significantly altered in chick oviducts by exogenous
      estrogen and those candidates included dexamethasone (DEX)-induced RAS-related
      protein 1 (RASD1). RAS-related protein 1, a member of the Ras family of monomeric
      G proteins, is involved in various cellular processes including cell growth,
      proliferation and differentiation, as well as a cell-signaling protein regulating
      hormonal actions. Although the RASD1 gene was first identified as a DEX (a
      corticosteroid) inducible gene, there is evidence that it is also an estrogen
      responsive gene. However, hormone-mediated expression and biological functions of
      RASD1 in the avian female reproductive system are poorly understood. Therefore,
      we tested the hypothesis that RASD1 may be involved in the development and
      remodeling of the chicken reproductive system as an estrogen-responsive gene.
      Here we demonstrate differential expression of RASD1 gene and candidate microRNAs
      (miRNAs) targeting chicken RASD1 transcripts in chicken oviducts in response to
      diesthylstilbestrol (DES, a synthetic non-steroidal estrogen) and the estrogen
      mediated molting process. Result of the present study indicated that expression
      of RASD1 messenger RNA (mRNA) increased in the developing oviducts of chicks
      treated with DES, particularly in the glandular (GE) and luminal (LE) epithelia
      of the magnum and the shell gland. Also, during induced molting by zinc feeding,
      RASD1 expression changed in concert with changes in concentrations of estrogen in
      blood of laying hens. Our results revealed that expression of RASD1 mRNA
      decreased as the oviduct regressed and then increased as the oviduct underwent re
      growth and recrudescence in hens. Furthermore, RASD1 mRNA was expressed
      predominantly in GE and LE of the oviduct of laying hens during regeneration of
      the oviduct after induced molting, but not during the period of regression of the
      oviduct during molting. In addition, the relative expression of candidate miRNAs
      (miR-30a-5p, miR-30b-5p, miR-30c-5p and miR-30d) regulating RASD1 transcripts
      changed in response to estrogen stimulation of chick oviducts. These results
      indicate that transcription of the RASD1 gene and miRNAs regulating post
      transcriptional aspects of expression of RASD1 are modulated by estrogen which is
      critical for growth, development, remodeling and maintenance of function of the
      chicken oviduct.

PMID- 29198268
TI  - The Many Sides of Hemispheric Asymmetry: A Selective Review and Outlook.
AB  - Hemispheric asymmetry is commonly viewed as a dual system, unique to humans, with
      the two sides of the human brain in complementary roles. To the contrary, modern
      research shows that cerebral and behavioral asymmetries are widespread in the
      animal kingdom, and that the concept of duality is an oversimplification. The
      brain has many networks serving different functions; these are differentially
      lateralized, and involve many genes. Unlike the asymmetries of the internal
      organs, brain asymmetry is variable, with a significant minority of the
      population showing reversed asymmetries or the absence of asymmetry. This
      variability may underlie the divisions of labor and the specializations that
      sustain social life. (JINS, 2017, 23, 710-718).

PMID- 29198269
TI  - Neuropsychological Investigations of Human Amnesia: Insights Into the Role of the
      Medial Temporal Lobes in Cognition.
AB  - The past 30 years of research on human amnesia has yielded important changes in
      our understanding of the role of the medial temporal lobes (MTL) in memory. On
      the one hand, this body of evidence has highlighted that not all types of memory
      are impaired in patients with MTL lesions. On the other hand, this research has
      made apparent that the role of the MTL extends beyond the domain of long-term
      memory, to include working memory, perception, and future thinking. In this
      article, we review the discoveries and controversies that have characterized this
      literature and that set the stage for a new conceptualization of the role of the
      MTL in cognition. This shift toward a more nuanced understanding of MTL function
      has direct relevance for a range of clinical disorders in which the MTL is
      implicated, potentially shaping not only theoretical understanding but also
      clinical practice. (JINS, 2017, 23, 732-740).

PMID- 29198270
TI  - Contributions to Understanding the Neuropsychology of Alcoholism: An INS Legacy.
AB  - Alcohol use disorder (AUD) has been a major cause of family, social, and personal
      strife for centuries, with current prevalence estimates of 14% for 12-month and
      29% lifetime AUD. Neuropsychological testing of selective cognitive, sensory, and
      motor functions complemented with in vivo brain imaging has enabled tracking the
      consequences of AUD, which follows a dynamic course of development, maintenance,
      and recovery or relapse. Controlled studies of alcoholism reviewed herein provide
      evidence for disruption of selective functions involving executive, visuospatial,
      mnemonic, emotional, and attentional processes, response inhibition, prosody, and
      postural stability and brain systems supporting these functions. On a hopeful
      front, longitudinal study provides convincing evidence for improvement in brain
      structure and function following sustained sobriety. These discoveries have a
      strong legacy in the International Neuropsychological Society (INS), starting
      from its early days when assumptions regarding which brain regions were disrupted
      relied solely on patterns of functional sparing and impairment deduced from
      testing. This review is based on the symposium presentation delivered at the 2017
      annual North American meeting of the INS in celebration of the 50th anniversary
      since its institution in 1967. In the spirit of the meeting's theme, "Binding the
      Past and Present," the lecture and this review recognized the past by focusing on
      early, rigorous neuropsychological studies of alcoholism and their influence on
      research currently conducted using imaging methods enabling hypothesis testing of
      brain substrates of observed functional deficits. (JINS, 2017, 23, 843-859).

PMID- 29198271
TI  - The Neuropsychology of Traumatic Brain Injury: Looking Back, Peering Ahead.
AB  - The past 50 years have been a period of exciting progress in neuropsychological
      research on traumatic brain injury (TBI). Neuropsychologists and
      neuropsychological testing have played a critical role in these advances. This
      study looks back at three major scientific advances in research on TBI that have
      been critical in pushing the field forward over the past several decades: The
      advent of modern neuroimaging; the recognition of the importance of non-injury
      factors in determining recovery from TBI; and the growth of cognitive
      rehabilitation. Thanks to these advances, we now have a better understanding of
      the pathophysiology of TBI and how recovery from the injury is also shaped by pre
      injury, comorbid, and contextual factors, and we also have increasing evidence
      that active interventions, including cognitive rehabilitation, can help to
      promote better outcomes. The study also peers ahead to discern two important
      directions that seem destined to influence research on TBI over the next 50
      years: the development of large, multi-site observational studies and randomized
      controlled trials, bolstered by international research consortia and the adoption
      of common data elements; and attempts to translate research into health care and
      health policy by the application of rigorous methods drawn from implementation
      science. Future research shaped by these trends should provide critical evidence
      regarding the outcomes of TBI and its treatment, and should help to disseminate
      and implement the knowledge gained from research to the betterment of the quality
      of life of persons with TBI. (JINS, 2017, 23, 806-817).

PMID- 29198273
TI  - The Neuropsychology of Movement and Movement Disorders: Neuroanatomical and
      Cognitive Considerations.
AB  - This paper highlights major developments over the past two to three decades in
      the neuropsychology of movement and its disorders. We focus on studies in healthy
      individuals and patients, which have identified cognitive contributions to
      movement control and animal work that has delineated the neural circuitry that
      makes these interactions possible. We cover advances in three major areas: (1)
      the neuroanatomical aspects of the "motor" system with an emphasis on multiple
      parallel circuits that include cortical, corticostriate, and corticocerebellar
      connections; (2) behavioral paradigms that have enabled an appreciation of the
      cognitive influences on the preparation and execution of movement; and (3)
      hemispheric differences (exemplified by limb praxis, motor sequencing, and motor
      learning). Finally, we discuss the clinical implications of this work, and make
      suggestions for future research in this area. (JINS, 2017, 23, 768-777).

PMID- 29198274
TI  - Fifty Years of Prefrontal Cortex Research: Impact on Assessment.
AB  - Our knowledge of the functions of the prefrontal cortex, often called executive,
      supervisory, or control, has been transformed over the past 50 years. After
      operationally defining terms for clarification, we review the impact of advances
      in functional, structural, and theoretical levels of understanding upon
      neuropsychological assessment practice as a means of identifying 11
      principles/challenges relating to assessment of executive function. Three of
      these were already known 50 years ago, and 8 have been confirmed or emerged
      since. Key themes over this period have been the emergence of the use of
      naturalistic tests to address issues of "ecological validity"; discovery of the
      complexity of the frontal lobe control system; invention of new tests for
      clinical use; development of key theoretical frameworks that address the issue of
      the role of prefrontal cortex systems in the organization of human cognition; the
      move toward considering brain systems rather than brain regions; the advent of
      functional neuroimaging, and its emerging integration into clinical practice.
      Despite these huge advances, however, practicing neuropsychologists are still
      desperately in need of new ways of measuring executive function. We discuss
      pathways by which this might happen, including decoupling the two levels of
      explanation (information processing; brain structure) and integrating very recent
      technological advances into the neuropsychologist's toolbox. (JINS, 2017, 23, 755
      767).

PMID- 29198272
TI  - Paradigm Shifts in the Neuropsychology of Epilepsy.
AB  - This article reviews the major paradigm shifts that have occurred in the area of
      the application of clinical and experimental neuropsychology to epilepsy and
      epilepsy surgery since the founding of the International Neuropsychological
      Society. The five paradigm shifts discussed include: 1) The neurobiology of
      cognitive disorders in epilepsy - expanding the landscape of syndrome-specific
      neuropsychological impairment; 2) pathways to comorbidities: bidirectional
      relationships and their clinical implications; 3) discovering quality of life:
      The concept, its quantification and applicability; 4) outcomes of epilepsy
      surgery: challenging conventional wisdom; and 5) Iatrogenic effects of treatment:
      cognitive and behavioral effects of antiepilepsy drugs. For each area we
      characterize the status of knowledge, the key developments that have occurred,
      and how they have altered our understanding of the epilepsies and their
      management. We conclude with a brief overview of where we believe the field will
      be headed in the next decade which includes changes in assessment paradigms,
      moving from characterization of comorbidities to interventions; increasing
      development of new measures, terminology and classification; increasing interest
      in neurodegenerative proteins; transitioning from clinical seizure features to
      modifiable risk factors; and neurobehavioral phenotypes. Overall, enormous
      progress has been made over the lifespan of the INS with promise of ongoing
      improvements in understanding of the cognitive and behavioral complications of
      the epilepsies and their treatment. (JINS, 2017, 23, 791-805).

PMID- 29198275
TI  - Emotions Are Rising: The Growing Field of Affect Neuropsychology.
AB  - Thirty years ago, the neuropsychology of emotion started to emerge as a
      mainstream topic. Careful examination of individual patients showed that emotion,
      like memory, language, and so on, could be differentially affected by brain
      disorders, especially in the right hemisphere. Since then, there has been
      accelerating interest in uncovering the neural architecture of emotion, and the
      major steps in this process of discovery over the past 3 decades are detailed in
      this review. In the 1990s, magnetic resonance imaging (MRI) scans provided
      precise delineation of lesions in the amygdala, medial prefrontal cortex, insula
      and somatosensory cortex as underpinning emotion disorders. At the same time,
      functional MRI revealed activation that was bilateral and also lateralized
      according to task demands. In the 2000s, converging evidence suggested at least
      two routes to emotional responses: subcortical, automatic and autonomic responses
      and slower, cortical responses mediating cognitive processing. The discovery of
      mirror neurons in the 1990s reinvigorated older views that simulation was the
      means to recognize emotions and empathize with others. More recently,
      psychophysiological research, revisiting older Russian paradigms, has contributed
      new insights into how autonomic and other physiological indices contribute to
      decision making (the somatic marker theory), emotional simulation, and social
      cognition. Finally, this review considers the extent to which these seismic
      changes in understanding emotional processes in clinical disorders have been
      reflected in neuropsychological practice. (JINS, 2017, 23, 719-731).

PMID- 29198276
TI  - Does Cannabis Use Cause Declines in Neuropsychological Functioning? A Review of
      Longitudinal Studies.
AB  - Cannabis use has been linked to impairments in neuropsychological functioning
      across a large and continually expanding body of research. Yet insight into
      underlying causal relations remains limited due to the historically cross
      sectional nature of studies in this area. Recently, however, studies have begun
      to use more informative design strategies to delineate these associations. The
      aim of this article is to provide a critical evaluation and review of research
      that uses longitudinal designs to examine the link between cannabis use and
      neuropsychological functioning. In summarizing the primary findings across these
      studies, this review suggests that cannabis use leads to neuropsychological
      decline. However, across most studies, these associations were modest, were
      present only for the group with the heaviest cannabis use, and were often
      attenuated (or no longer significant) after controlling for potential confounding
      variables. Future studies with neuropsychological data before and after
      initiation of cannabis use, along with careful measurement and control of "shared
      risk factors" between cannabis use and poorer neuropsychological outcomes, are
      needed to better understand who, and under what conditions, is most vulnerable to
      cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893-902).

PMID- 29198278
TI  - Brain-Based Biomarkers for the Treatment of Depression: Evolution of an Idea.
AB  - An ambition of depression biomarker research is to augment psychometric and
      cognitive assessment of clinically relevant phenomena with neural measures.
      Although such applications have been slow to arrive, we observe a steady
      evolution of the idea and anticipate emerging technologies with some optimism. To
      highlight critical themes and innovations in depression biomarker research, we
      take as our point of reference a specific research narrative. We begin with an
      early model of frontal-limbic dysfunction, which represents a conceptual shift
      from localized pathology to understanding symptoms as an emergent property of
      distributed networks. Over the decades, this model accommodates perspectives from
      neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past
      insight as more complex methods become available. We also track the expanding
      mission of brain biomarker research: from the development of diagnostic tools to
      treatment selection algorithms, measures of neurocognitive functioning and novel
      targets for neuromodulation. To conclude, we draw from this particular research
      narrative future directions for biomarker research. We emphasize integration of
      measurement modalities to describe dynamic change in domain-general networks, and
      we speculate that a brain-based framework for psychiatric problems may dissolve
      classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870-880).

PMID- 29198277
TI  - Attention-Deficit/Hyperactivity Disorder: A Historical Neuropsychological
      Perspective.
AB  - The behavior patterns of hyperactivity, impulsivity and inattention that would
      ultimately become recognized as Attention-Deficit Hyperactivity Disorder (ADHD)
      have been described for centuries. Nevertheless, in the past 35 years, advances
      in diagnostic methods, identification of biomarkers, and treatments have advanced
      at an exponential rate. ADHD is now recognized as the most common behavioral
      disorder of childhood, with risks extending well into adulthood for both males
      and females, leading to its identification as a significant public health issue.
      This historical neuropsychological review of ADHD emphasizes scientific
      highlights in the past 35 years related to ADHD, including the evolution of the
      diagnosis (from Hyperkinetic Reaction of Childhood to ADHD), influential theories
      (executive functions, cognitive-energetic, delay aversion), landmark treatment
      studies (Multimodal Treatment of ADHD [MTA] and Preschool ADHD Treatment Study
      [PATS]), and advances in brain mapping techniques (anatomic, functional, and
      resting state magnetic resonance imaging, diffusion tensor imaging). The review
      concludes by highlighting the challenges of studying and treating a heterogeneous
      neurodevelopmental disorder like ADHD, with emphasis on associated disorders and
      conditions (learning disabilities, sluggish cognitive tempo), special populations
      (girls, preschoolers, adults), and recommendations for scientific inquiry in the
      next 35 years. Neuropsychologists are well positioned to address the clinical and
      research challenges of the next generation of studies, especially involving
      advances in understanding the sexual dimor.phism, full developmental course, and
      dynamic risks associated with ADHD. (JINS, 2017, 23, 916-929).

PMID- 29198279
TI  - Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward.
AB  - The neuropsychological aspects of multiple sclerosis (MS) have evolved over the
      past three decades. What was once thought to be a rare occurrence, cognitive
      dysfunction is now viewed as one of the most disabling symptoms of the disease,
      with devastating effects on patients' quality of life. This selective review will
      highlight major innovations and scientific discoveries in the areas of
      neuropathology, neuroimaging, diagnosis, and treatment that pertain to our
      understanding of the neuropsychological aspects of MS. Specifically, we focus on
      the recent discovery that MS produces pathogical lesions of gray matter (GM) that
      have consequences for cognitive functions. Methods for imaging these GM lesions
      in MS are discussed along with multimodal imaging studies that integrate
      structural and functional imaging methods to provide a better understanding of
      the relationship between cognitive test performance and functional reserve.
      Innovations in the screening and comprehensive assessment of cognitive disorders
      are presented along with recent research that examines cognitive dysfunction in
      pediatric MS. Results of innovative outcome studies in cognitive rehabilitation
      are discussed. Finally, we highlight trends for potential future innovations over
      the next decade. (JINS, 2017, 23, 832-842).

PMID- 29198281
TI  - Neuropsychological Assessment: Past and Future.
AB  - Neuropsychological assessment tools are the staple of our field. The development
      of standardized metrics sensitive to brain-behavior relationships has shaped the
      neuropsychological questions we can ask, our understanding of discrete brain
      functions, and has informed the detection and treatment of neurological
      disorders. We identify key turning points and innovations in neuropsychological
      assessment over the past 40-50 years that highlight how the tools used in common
      practice today came to be. Also selected for emphasis are several exciting lines
      of research and novel approaches that are underway to further probe and
      characterize brain functions to enhance diagnostic and treatment outcomes. We
      provide a brief historical review of different clinical neuropsychological
      assessment approaches (Lurian, Flexible and Fixed Batteries, Boston Process
      Approach) and critical developments that have influenced their interpretation
      (normative standards, cultural considerations, longitudinal change, common metric
      batteries, and translational assessment constructs). Lastly, we discuss growing
      trends in assessment including technological advances, efforts to integrate
      neuropsychology across disciplines (e.g., primary care), and changes in
      neuropsychological assessment infrastructure. Neuropsychological assessment has
      undergone massive growth in the past several decades. Nonetheless, there remain
      many unanswered questions and future challenges to better support measurement
      tools and translate assessment findings into meaningful recommendations and
      treatments. As technology and our understanding of brain function advance,
      efforts to support infrastructure for both traditional and novel assessment
      approaches and integration of complementary brain assessment tools from other
      disciplines will be integral to inform brain health treatments and promote the
      growth of our field. (JINS, 2017, 23, 778-790).

PMID- 29198280
TI  - Alzheimer's Disease: Past, Present, and Future.
AB  - Although dementia has been described in ancient texts over many centuries (e.g.,
      "Be kind to your father, even if his mind fail him." - Old Testament: Sirach
      3:12), our knowledge of its underlying causes is little more than a century old.
      Alzheimer published his now famous case study only 110 years ago, and our modern
      understanding of the disease that bears his name, and its neuropsychological
      consequences, really only began to accelerate in the 1980s. Since then we have
      witnessed an explosion of basic and translational research into the causes,
      characterizations, and possible treatments for Alzheimer's disease (AD) and other
      dementias. We review this lineage of work beginning with Alzheimer's own writings
      and drawings, then jump to the modern era beginning in the 1970s and early 1980s
      and provide a sampling of neuropsychological and other contextual work from each
      ensuing decade. During the 1980s our field began its foundational studies of
      profiling the neuropsychological deficits associated with AD and its
      differentiation from other dementias (e.g., cortical vs. subcortical dementias).
      The 1990s continued these efforts and began to identify the specific cognitive
      mechanisms affected by various neuropathologic substrates. The 2000s ushered in a
      focus on the study of prodromal stages of neurodegenerative disease before the
      full-blown dementia syndrome (i.e., mild cognitive impairment). The current
      decade has seen the rise of imaging and other biomarkers to characterize
      preclinical disease before the development of significant cognitive decline.
      Finally, we suggest future directions and predictions for dementia-related
      research and potential therapeutic interventions. (JINS, 2017, 23, 818-831).

PMID- 29198282
TI  - Neuropsychology of Learning Disabilities: The Past and the Future.
AB  - Over the past 50 years, research on children and adults with learning
      disabilities has seen significant advances. Neuropsychological research
      historically focused on the administration of tests sensitive to brain
      dysfunction to identify putative neural mechanisms underlying learning
      disabilities that would serve as the basis for treatment. Led by research on
      classifying and identifying learning disabilities, four pivotal changes in
      research paradigms have produced a contemporary scientific, interdisciplinary,
      and international understanding of these disabilities. These changes are (1) the
      emergence of cognitive science, (2) the development of quantitative and molecular
      genetics, (3) the advent of noninvasive structural and functional neuroimaging,
      and (4) experimental trials of interventions focused on improving academic skills
      and addressing comorbid conditions. Implications for practice indicate a need to
      move neuropsychological assessment away from a primary focus on systematic,
      comprehensive assessment of cognitive skills toward more targeted performance
      based assessments of academic achievement, comorbid conditions, and intervention
      response that lead directly to evidence-based treatment plans. Future research
      will continue to cross disciplinary boundaries to address questions regarding the
      interaction of neurobiological and contextual variables, the importance of
      individual differences in treatment response, and an expanded research base on
      (a) the most severe cases, (b) older people with LDs, and (c) domains of math
      problem solving, reading comprehension, and written expression. (JINS, 2017, 23,
      930-940).

PMID- 29198284
TI  - Facilitating Autism Research.
AB  - Early autism research focused on behavior and cognition. In recent decades, the
      pace of research has accelerated, and advances in imaging and genetics have
      allowed the accumulation of biological data. Nevertheless, a coherent picture of
      the syndrome at either phenotypic or biological level has not emerged. We see two
      fundamental obstacles to progress in basic understanding of autism. First, the
      two defining features (impairment in social interactions and communication, and
      restricted, repetitive behaviors and interests) are historically seen as
      integrally related. Others hold that these two major traits are fractionable and
      must be studied independently, casting doubt on autism as a coherent syndrome.
      Second, despite much recent research on brain structure and function,
      environmental factors, and genetics/genomics, findings on the biological level
      have not generally aligned well with those on the phenotypic level. In the first
      two sections, we explore these challenges, and in the third section, we review
      approaches that may facilitate progress, such as (1) including in studies all
      individuals defined by social impairment without regard to repetitive behaviors,
      (2) forming narrowly defined subtypes by thorough characterization on specific
      features, both diagnostic and non-diagnostic, (3) focusing on characteristics
      that may be relatively robust to environmental influence, (4) studying children
      as early as possible, minimizing environmental influence, and including
      longitudinal course as an important part of the phenotype, (5) subtyping by
      environmental risk factors, (6) distinguishing between what participants can do
      and what they typically do, and (7) aggregating large data sets across sites.
      (JINS, 2017, 23, 903-915).

PMID- 29198285
TI  - Evolving Notions of Schizophrenia as a Developmental Neurocognitive Disorder.
AB  - We review the changing conceptions of schizophrenia over the past 50 years as it
      became understood as a disorder of brain function and structure in which
      neurocognitive dysfunction was identified at different illness phases. The
      centrality of neurocognition has been recognized, especially because
      neurocognitive deficits are strongly related to social and role functioning in
      the illness, and as a result neurocognitive measures are used routinely in
      clinical assessment of individuals with schizophrenia. From the original
      definitions of the syndrome of schizophrenia in the early 20th century, impaired
      cognition, especially attention, was considered to be important. Neurocognitive
      impairments are found in the vast majority of individuals with schizophrenia, and
      they vary from mild, relatively restricted deficits, to dementia-like syndromes,
      as early as the first psychotic episode. Neurocognitive deficits are found in the
      premorbid phase in a substantial minority of pre-teenage youth who later develop
      schizophrenia, and they apparently worsen by the prodromal, high-risk phase in a
      majority of those who develop the illness. While there is limited evidence for
      reversibility of impairments from pharmacological interventions in schizophrenia,
      promising results have emerged from cognitive remediation studies. Thus, we
      expect cognitive interventions to play a larger role in schizophrenia in the
      coming years. Moreover, because youth at risk for schizophrenia can be identified
      by an emergent high-risk syndrome, earlier interventions might be applied in a
      pre-emptive way to reduce disability and improve adaptation. The notion of
      schizophrenia as a developmental neurocognitive disorder with stages opens up a
      window of possibilities for earlier interventions. (JINS, 2017, 23, 881-892).

PMID- 29198283
TI  - HIV-Associated Neurocognitive Disorders: A Global Perspective.
AB  - The present review on HIV-associated neurocognitive disorders (HAND) provides a
      worldwide overview of studies that have investigated the rate and
      neuropsychological (NP) profile of HAND research since the inception of the 2007
      HAND diagnostic nomenclature. In the first part, the review highlights some of
      the current controversies around HAND prevalence rates. In the second part, the
      review critically assesses some solutions to move the field forward. In the third
      part, we present the cross-sectional NP profile in non-Western HIV+ cohorts and
      in relation to Western cohorts' findings. The adopted global perspective
      highlights the successful expansion of NP studies in HIV infection to culturally
      diverse low- to medium-income countries with high HIV burden. These studies have
      produced interestingly similar rates of HAND whether patients were naive or
      treated and/or virally suppressed compared to the rich income countries where the
      NP research in NeuroHIV has originated. The perspective also demonstrates that
      globally, the group which is the most representative of the HIV epidemic, and
      thus at risk for HAND are persons with chronic HIV infection and survivors of
      past immunosuppression, while in relative terms, those who have been treated
      early with long-term viral suppression represent a minority. In the last part, we
      present a review of the naturalistic longitudinal NP global studies in
      HIV+cohorts, discuss the role of longitudinal design in solving issues around the
      question of asymptomatic neurocognitive impairment, and the question of biomarker
      discovery. Finally, we conclude by calling for greater methods and data
      harmonization at a global level. (JINS, 2017, 23, 860-869).

PMID- 29198286
TI  - What Do Language Disorders Reveal about Brain-Language Relationships? From
      Classic Models to Network Approaches.
AB  - Studies of language disorders have shaped our understanding of brain-language
      relationships over the last two centuries. This article provides a review of this
      research and how our thinking has changed over the years regarding how the brain
      processes language. In the 19th century, a series of famous case studies linked
      distinct speech and language functions to specific portions of the left
      hemisphere of the brain, regions that later came to be known as Broca's and
      Wernicke's areas. One hundred years later, the emergence of new brain imaging
      tools allowed for the visualization of brain injuries in vivo that ushered in a
      new era of brain-behavior research and greatly expanded our understanding of the
      neural processes of language. Toward the end of the 20th century, sophisticated
      neuroimaging approaches allowed for the visualization of both structural and
      functional brain activity associated with language processing in both healthy
      individuals and in those with language disturbance. More recently, language is
      thought to be mediated by a much broader expanse of neural networks that covers a
      large number of cortical and subcortical regions and their interconnecting fiber
      pathways. Injury to both grey and white matter has been seen to affect the
      complexities of language in unique ways that have altered how we think about
      brain-language relationships. The findings that support this paradigm shift are
      described here along with the methodologies that helped to discover them, with
      some final thoughts on future directions, techniques, and treatment interventions
      for those with communication impairments. (JINS, 2017, 23, 741-754).

PMID- 29198287
TI  - A cross-sectional examination of the prevalence of psychotropic medications for
      people living with dementia in Australian long-term care facilities: issues of
      concern.
AB  - : ABSTRACTBackground:Behavioral and psychological symptoms of dementia (BPSD) are
      a common problem in long-term care facilities (LTC). Clinical guidelines dictate
      that first-line treatments for BPSD are psychosocial and behavioral
      interventions; if these are unsuccessful, psychotropic medications may be trialed
      at low doses and their effects can be monitored. METHODS: There have previously
      been no studies with nationally representative samples to investigate
      psychotropic administration in LTCs in Australia. This study determines the
      prevalence of psychotropic administration in a representative stratified random
      sample of 446 residents living with dementia from 53 Australian LTCs.
      Questionnaire and medical chart data in this study is drawn from a larger cross
      sectional, mixed methods study on quality of life in Australian LTCs. RESULTS: It
      was found that 257 (58%) residents were prescribed psychotropic medications
      including: antipsychotics (n = 160, 36%), benzodiazepines (n = 136, 31%),
      antidepressants (n = 117, 26%), and anti-dementia medications (n = 9, 2%). BPSD
      were found to be very common in the sample, with 82% (n = 364) of participants
      experiencing at least one BPSD. The most prevalent BPSD were depression (n = 286,
      70%) and agitation (n = 299, 67%). CONCLUSIONS: Although detailed background
      information was not collected on individual cases, the prevalence found is
      indicative of systematic industry-wide, over-prescription of psychotropic
      medications as a first-line treatment for BPSD. This study highlights a clear
      need for further research and interventions in this area.

PMID- 29198288
TI  - Integrating diverse forage sources reduces feed gaps on mixed crop-livestock
      farms.
AB  - Highly variable climates induce large variability in the supply of forage for
      livestock and so farmers must manage their livestock systems to reduce the risk
      of feed gaps (i.e. periods when livestock feed demand exceeds forage supply).
      However, mixed crop-livestock farmers can utilise a range of feed sources on
      their farms to help mitigate these risks. This paper reports on the development
      and application of a simple whole-farm feed-energy balance calculator which is
      used to evaluate the frequency and magnitude of feed gaps. The calculator matches
      long-term simulations of variation in forage and metabolisable energy supply from
      diverse sources against energy demand for different livestock enterprises.
      Scenarios of increasing the diversity of forage sources in livestock systems is
      investigated for six locations selected to span Australia's crop-livestock zone.
      We found that systems relying on only one feed source were prone to higher risk
      of feed gaps, and hence, would often have to reduce stocking rates to mitigate
      these risks or use supplementary feed. At all sites, by adding more feed sources
      to the farm feedbase the continuity of supply of both fresh and carry-over forage
      was improved, reducing the frequency and magnitude of feed deficits. However,
      there were diminishing returns from making the feedbase more complex, with
      combinations of two to three feed sources typically achieving the maximum
      benefits in terms of reducing the risk of feed gaps. Higher stocking rates could
      be maintained while limiting risk when combinations of other feed sources were
      introduced into the feedbase. For the same level of risk, a feedbase relying on a
      diversity of forage sources could support stocking rates 1.4 to 3 times higher
      than if they were using a single pasture source. This suggests that there is
      significant capacity to mitigate both risk of feed gaps at the same time as
      increasing 'safe' stocking rates through better integration of feed sources on
      mixed crop-livestock farms across diverse regions and climates.

PMID- 29198289
TI  - The Incidence and Characterization of Globus Sensation, Dysphagia, and
      Odynophagia Following Surgery for Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: To determine the incidence, duration, and predictors of
      swallowing-related symptoms following upper airway surgery for obstructive sleep
      apnea. METHODS: Adults (age 18 years or older) who underwent surgery for
      obstructive sleep apnea at a tertiary care institution from January 2012 to
      December 2015 were retrospectively reviewed. The incidence, duration, and
      associated factors of postoperative swallowing complaints were evaluated.
      RESULTS: A total of 130 patients (135 surgical encounters) met criteria for
      inclusion. There were 91 men (70.0%) and 39 women (30.0%) with a median age of 60
      years (range: 19-79). Presurgical diagnosis of gastroesophageal reflux disease
      was present in 57 patients (43.8%). An average of 2.1 procedures (+/- 0.8) were
      conducted at each encounter. Uvulopalatopharyngoplasty (54.8%) was the most
      common followed by radiofrequency ablation of the soft palate (34.8%) and tongue
      base (29.6%). Postoperatively, 25 patients (19.8%) complained of dysphagia, 14
      (10.9%) of globus, and 9 (6.7%) of odynophagia. Preoperative gastroesophageal
      reflux (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.41-11.91) and hyoid
      myotomy with suspension (OR 4.88, 95% CI 1.34-17.77) were significant predictors
      for dysphagia. Radiofrequency ablation of the tongue base (OR 5.00, 95% CI 1.28
      19.50) was a predictor for globus sensation. Median symptom durations, in months,
      were 4.0 for dysphagia, 7.3 for globus, and 3.0 for odynophagia. CONCLUSIONS:
      Preoperative gastroesophageal reflux and hyoid myotomy with suspension procedure
      were associated with postoperative dysphagia whereas radiofrequency ablation of
      the tongue base was associated with globus. These findings can assist surgeons in
      providing preoperative counseling and postoperative supportive measures regarding
      dysphagic symptoms following sleep surgery.

PMID- 29198290
TI  - Hypnosis Intervention Effects on Sleep Outcomes: A Systematic Review.
AB  - STUDY OBJECTIVES: Sleep improvement is a promising target for preventing and
      modifying many health problems. Hypnosis is considered a cost-effective and safe
      intervention with reported benefits for multiple health conditions. There is a
      growing body of research assessing the efficacy of hypnosis for various health
      conditions in which sleep was targeted as a primary or secondary outcome. This
      review aimed to investigate the effects of hypnosis interventions on sleep, to
      describe the hypnotic procedures, and to evaluate potential adverse effects of
      hypnosis. METHODS: We reviewed studies (prior to January 2017) using hypnosis in
      adults for sleep problems and other conditions comorbid with sleep problems, with
      at least one sleep outcome measure. Randomized controlled trials and other
      prospective studies were included. RESULTS: One hundred thirty-nine nonduplicate
      abstracts were screened, and 24 of the reviewed papers were included for
      qualitative analysis. Overall, 58.3% of the included studies reported hypnosis
      benefit on sleep outcomes, with 12.5% reporting mixed results, and 29.2%
      reporting no hypnosis benefit; when only studies with lower risk of bias were
      reviewed the patterns were similar. Hypnosis intervention procedures were
      summarized and incidence of adverse experiences assessed. CONCLUSIONS: Hypnosis
      for sleep problems is a promising treatment that merits further investigation.
      Available evidence suggests low incidence of adverse events. The current evidence
      is limited because of few studies assessing populations with sleep complaints,
      small samples, and low methodological quality of the included studies. Our review
      points out some beneficial hypnosis effects on sleep but more high-quality
      studies on this topic are warranted.

PMID- 29198291
TI  - Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data
      Analysis.
AB  - STUDY OBJECTIVES: There is a lack of data regarding adherence trajectories when
      switching from continuous positive airway pressure (CPAP) to adaptive
      servoventilation (ASV) in the context of persistent or treatment-emergent central
      sleep apnea (CSA). This study investigated 90-day adherence rates in patients
      with sleep apnea based on the type of positive airway pressure (PAP) device used
      and any switching of PAP modality over time. METHODS: Telemonitoring data were
      obtained from a United States PAP database. Eligible patients were a 30% random
      sample who started PAP, plus all who started ASV, from January 1, 2015 to October
      2, 2015. All received PAP and had at least one session with usage of 1 hour or
      more. Adherence and device usage were determined in three groups: started on CPAP
      and stayed on CPAP (CPAP only); started on ASV and stayed on ASV (ASV only);
      started on CPAP, switched to ASV (Switch). The United States Medicare definition
      of adherence was used. RESULTS: The study included 198,890 patients; 189,724
      (CPAP only), 8,957 (ASV only) and 209 (Switch). In the Switch group, average
      apnea-hypopnea index decreased significantly on ASV versus CPAP. At 90 days,
      adherence rates were 73.8% and 73.2% in the CPAP only and ASV only groups. In the
      Switch group, CPAP adherence was 62.7%, improving to 76.6% after the switch to
      ASV. Mean device usage at 90 days was 5.27, 5.31, and 5.73 h/d in the CPAP only,
      ASV only, and Switch groups, respectively. CONCLUSIONS: Treatment-emergent or
      persistent CSA during CPAP reduced therapy adherence, but adherence improved
      early after switching from CPAP to ASV.

PMID- 29198292
TI  - Polysomnography-Detected Bruxism in Children is Associated With Somatic
      Complaints But Not Anxiety.
AB  - STUDY OBJECTIVES: Sleep bruxism (SB) is common in children and is associated with
      somatic symptoms and sleep disturbance. Etiological theories posit the role of
      anxiety, suggesting youth with anxiety disorders may be at high risk for SB, but
      empirical data are lacking. Furthermore, parent report rather than
      polysomnography (PSG) has been used to examine SB-anxiety relationships in
      children. We examined rates of PSG-detected compared to parent-reported SB in
      children with generalized anxiety disorder (GAD) and healthy controls.
      Associations among SB, somatic complaints, and sleep disturbance were also
      examined. METHODS: Thirty-one children, aged 7-11 years, completed 1 night of PSG
      monitoring and 7 daily reports of somatic symptoms. Bruxism events were scored
      during stage R sleep, stage N1 sleep, and stage N2 sleep. RESULTS: Almost one
      third of children showed evidence of SB based on PSG. No associations were
      identified between parent-reported and PSG-detected SB. Rates of SB did not
      differ between anxious and control groups, though children with GAD showed more
      tonic bruxisms during stage R sleep. Presence of SB predicted more muscle aches
      and stomach aches, and children with SB had more awake time after sleep onset
      than those without bruxism. CONCLUSIONS: Results indicate poor concordance
      between PSG-detected and parent-reported SB in children, suggesting that parent
      report alone is not a reliable method for detection. The lack of association
      between SB and anxiety status suggests that stress sensitivity rather than
      anxiety per se may be predictive of SB. Associations between SB, somatic
      symptoms, and sleep disturbance are congruent with the broader literature.

PMID- 29198293
TI  - Comparison of Subjective Sleep Quality of Long-Term Residents at Low and High
      Altitudes: SARAHA Study.
AB  - STUDY OBJECTIVES: To study the effect of altitude on subjective sleep quality in
      populations living at high and low altitudes after excluding cases of restless
      legs syndrome (RLS). METHODS: This population-based study was conducted at three
      different altitudes (400 m, 1,900-2,000 m, and 3,200 m above sea level). All
      consenting subjects available from random stratified sampling in the Himalayan
      and sub-Himalayan regions of India were included in the study (ages 18 to 84
      years). Sleep quality and RLS status were assessed using validated translations
      of Pittsburgh Sleep Quality Index (PSQI) and Cambridge Hopkins RLS diagnostic
      questionnaire. Recent medical records were screened to gather data for medical
      morbidities. RESULTS: In the total sample of 1,689 participants included, 55.2%
      were women and average age of included subjects was 35.2 (+/- 10.9) years. In
      this sample, overall 18.4% reported poor quality of sleep (PSQI >= 5). Poor
      quality of sleep was reported more commonly at high altitude compared to low
      altitude (odds ratio [OR] = 2.65; 95% CI = 1.9-3.7; P < .001). It was more
      frequently reported among patients with RLS (29.7% versus 17.1% without RLS; P <
      .001). Other factors that were associated with poor quality of sleep were male
      sex, smoking, chronic obstructive pulmonary disease (COPD), and varicose veins.
      Binary logistic regression indicated that COPD (OR = 1.97; 95% CI = 1.36-2.86; P
      < .001), high altitude (OR = 2.22; 95% CI = 1.55-3.18; P < .001), and RLS (OR =
      1.66; 95% CI = 1.12-2.46; P = .01) increased the odds for poor quality of sleep.
      CONCLUSIONS: This study showed that poor quality of sleep was approximately twice
      as prevalent at high altitudes compared to low altitudes even after removing the
      potential confounders such as RLS and COPD.

PMID- 29198295
TI  - The Effect of Systematic Light Exposure on Sleep in a Mixed Group of Fatigued
      Cancer Survivors.
AB  - STUDY OBJECTIVES: Sleep disturbances are commonly reported by cancer survivors.
      Systematic light exposure using bright light has been used to improve sleep in
      other populations. In this secondary data analysis, the effect of morning
      administration of bright light on sleep and sleep quality was examined in a mixed
      group of fatigued cancer survivors. METHODS: Forty-four cancer survivors screened
      for cancer-related fatigue were randomized to either a bright white light or a
      comparison dim red light condition. Participants were instructed to use a light
      box every morning for 30 minutes for 4 weeks. Wrist actigraphy and the Pittsburgh
      Sleep Quality Index were administered at 4 time points: prior to light treatment
      (baseline), 2 weeks into the intervention, during the last week of the
      intervention, and 3 weeks postintervention. Thirty-seven participants completed
      the end-of-intervention assessment. RESULTS: Repeated-measures linear mixed
      models indicated a statistically significant time * treatment group interaction
      effect with sleep efficiency improving more in the bright light condition over
      time compared with the dim light condition (F3,42 = 5.55; P = .003) with a large
      effect size (partial eta2 = 0.28). By the end of the intervention and 3 weeks
      postintervention, mean sleep efficiency in the bright light group was in the
      normal range. Medium to large effect sizes were also seen in sleep quality, total
      sleep time, and wake after sleep onset for participants favoring the bright light
      condition. CONCLUSIONS: The results suggest that systematic bright light exposure
      in the morning may have beneficial effects on sleep in fatigued cancer survivors.
      Larger scale efficacy trials are warranted. CLINICAL TRIAL REGISTRATION:
      Registry: ClinicalTrials.gov, Title: Treating Cancer-Related Fatigue Through
      Systematic Light Exposure, Identifier: NCT01873794, URL:
      https://clinicaltrials.gov/ct2/show/NCT01873794.

PMID- 29198294
TI  - Sleep Quality, Sleep Duration, and the Risk of Coronary Heart Disease: A
      Prospective Cohort Study With 60,586 Adults.
AB  - STUDY OBJECTIVES: There is limited information on the relationship between risk
      of cardiovascular disease and the joint effects of sleep quality and sleep
      duration, especially from large, prospective, cohort studies. This study is to
      prospectively investigate the joint effects of sleep quality and sleep duration
      on the development of coronary heart disease. METHODS: This study examined 60,586
      adults aged 40 years or older. A self-administered questionnaire was used to
      collect information on sleep quality and sleep duration as well as a wide range
      of potential confounders. Events of coronary heart disease were self-reported in
      subsequent medical examinations. Two types of Sleep Score (multiplicative and
      additive) were constructed to reflect the participants' sleep profiles,
      considering both sleep quality and sleep duration. The Cox regression model was
      used to estimate the hazard ratio (HR) and the 95% confidence interval (CI).
      RESULTS: A total of 2,740 participants (4.5%) reported new events of coronary
      heart disease at follow-up. For sleep duration, participants in the group of < 6
      h/d was significantly associated with an increased risk of coronary heart disease
      (HR: 1.13, 95% CI: 1.04-1.23). However, the association in the participants with
      long sleep duration (> 8 h/d) did not reach statistical significance (HR: 1.11,
      95% CI: 0.98-1.26). For sleep quality, both dreamy sleep (HR: 1.21, 95% CI: 1.10
      1.32) and difficult to fall asleep/use of sleeping pills or drugs (HR: 1.40, 95%
      CI: 1.25-1.56) were associated with an increased risk of the disease.
      Participants in the lowest quartile of multiplicative Sleep Score (HR: 1.31, 95%
      CI: 1.16-1.47) and of additive sleep score (HR: 1.31, 95% CI: 1.16-1.47) were
      associated with increased risk of coronary heart disease compared with those in
      the highest quartile. CONCLUSIONS: Both short sleep duration and poor sleep
      quality are associated with the risk of coronary heart disease. The association
      for long sleep duration does not reach statistical significance. Lower Sleep
      Score (poorer sleep profile) increases the risk of coronary heart disease,
      suggesting the importance of considering sleep duration and sleep quality
      together when developing strategies to improve sleep for cardiovascular disease
      prevention.

PMID- 29198296
TI  - Variable Response to CPAP in a Case of Severe Obstructive Sleep Apnea: An Unusual
      Cause.
AB  - ABSTRACT: The objective of this report is to present clinical and scientific
      evidence to support the role of head position in the management of obstructive
      sleep apnea (OSA) with positive airway pressure. OSA, characterized by repetitive
      obstruction of the upper is a common medical condition associated with daytime
      somnolence, morning headaches, mood disturbances, and a variety of
      cardiopulmonary complications. The role of head position during obstructive
      respiratory events has been largely overlooked. We present a case where OSA
      severity decreased significantly with the head rotated in the right lateral
      position compared to head position in the neutral and left position. This case
      demonstrates an important influence of head position during continuous positive
      airway pressure titration, independent of trunk position and sleep stage, in
      patients with OSA, and highlights the utility of the video polysomnography for
      identifying the variant.

PMID- 29198297
TI  - Sleep Apnea in Patients Hospitalized With Acute Ischemic Stroke: Underrecognition
      and Associated Clinical Outcomes.
AB  - STUDY OBJECTIVES: To evaluate clinical recognition of sleep apnea and related
      outcomes in patients hospitalized with acute ischemic stroke. METHODS: A
      retrospective study of all patients hospitalized with acute ischemic stroke from
      April 2008 to December 2014. The primary predictor and outcome variables were
      sleep apnea and hospital mortality, respectively. Secondary outcomes were
      mechanical ventilation, hospital length of stay, and the survivor's functional
      level by the modified Rankin scale. A sensitivity multivariate regression
      analysis included the propensity score for cardiovascular comorbidities and sleep
      apnea. RESULTS: Of 989 patients, 190 (19%) were considered to have sleep apnea.
      Only 42 patients (22%) received any treatment for sleep apnea during the hospital
      stay. Despite higher prevalence of cardiovascular comorbidities, the patients
      with sleep apnea had lower hospital mortality, 1% versus 5.6% in patients without
      sleep apnea (odds ratio [OR] 0.18; 95% confidence interval [CI], 0.03-0.58, P =
      .002). Only the National Institutes of Health Stroke Scale (NIHSS) and the
      Glasgow coma scale (GCS) were significant predictors of adjusted hospital
      mortality (OR 1.06, 95% CI 1.01-1.11, P = .01 and OR 0.61, 95% CI 0.51-0.69, P <=
      .001, respectively). A composite clinical propensity score for sleep apnea and
      cardiovascular comorbidities was significantly associated with decreased
      mortality, independent to either NIHSS (OR 0.11, 95% CI 0.017-0.71; P = .02) or
      GCS (OR 0.07, 95% CI 0.01-0.52; P = .01). CONCLUSIONS: Prevalence of sleep apnea
      in our study was low, likely because of clinical underrecognition. Despite having
      more cardiovascular disease, the patients with acute stroke and sleep apnea had
      less severe neurological injury and lower unadjusted mortality than those without
      a history of sleep apnea.

PMID- 29198298
TI  - Treatment for Insomnia in 2017: "Don't Ask, Don't Treat".

PMID- 29198299
TI  - Patients With Obstructive Sleep Apnea Are Over Four Times More Likely to Suffer
      From Psoriasis Than the General Population.

PMID- 29198300
TI  - Sleep and Breast Cancer in the Western New York Exposures and Breast Cancer (WEB)
      Study.
AB  - STUDY OBJECTIVES: Night shift work is associated with increased breast cancer
      risk, possibly from altered sleep. Epidemiologic evidence is sparse regarding
      sleep disturbances and breast cancer tumor markers. We examined sleep disturbance
      in association with breast tumor aggressiveness and mortality following
      diagnosis. METHODS: We analyzed associations of measures of sleep disturbance in
      a sample of 1,122 incident breast cancer cases from the Western New York
      Exposures and Breast Cancer (WEB) Study. Sleep disturbance was assessed using
      self-administered questionnaires; responses about difficulty falling asleep,
      waking up frequently, having trouble staying asleep, and waking up feeling tired
      and worn out were used to create a summary sleep disturbance score. We used
      general linear models to examine associations of sleep disturbance with markers
      of tumor aggressiveness among cases: estrogen receptor (ER) status, progesterone
      receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status;
      tumor size, stage, grade, lymph node involvement, and presence of metastasis. In
      addition, we examined the association between sleep disturbance and survival
      using Cox regression. RESULTS: Among breast cancer cases, sleep disturbance was
      higher for women with ER- / PR- tumors compared to women with ER+ / PR+ tumors,
      even after adjusting for potential covariates (P for trend = .02). Results
      suggest that the association of sleep quality differs by menopausal status, where
      mild sleep disturbance is associated with higher breast cancer mortality in
      premenopausal women; however, we had a relatively small sample size. CONCLUSIONS:
      Sleep disturbance may be associated with aggressive subtypes of breast cancer;
      however, further studies are needed.

PMID- 29198301
TI  - The MSLT is Repeatable in Narcolepsy Type 1 But Not Narcolepsy Type 2: A
      Retrospective Patient Study.
AB  - STUDY OBJECTIVES: To examine repeatability of Multiple Sleep Latency Test (MSLT)
      results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the
      criteria of the International Classification of Sleep Disorders, Third Edition
      (ICSD-3). METHODS: Repeatability of the MSLT was retrospectively evaluated in NT1
      (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had
      documented HLA-DQB1*06:02 status and/or hypocretin-1 levels from cerebrospinal
      fluid. All subjects had undergone 2 MSLTs (>= 1 meeting ICSD-3 criteria for
      narcolepsy). Repeatability was explored in children versus adults and in those on
      versus not on medication(s). Subsample and multivariate analysis were performed.
      RESULTS: Both MSLTs in unmedicated patients were positive for narcolepsy in 78%,
      18%, and 7% of NT1, NT2, and controls, respectively. NT2 cases changed to
      idiopathic hypersomnia or to a negative MSLT 26% and 57% of the time,
      respectively. Although NT1 cases were 10 to 14 times more likely to demonstrate a
      second positive MSLT compared to NT2 cases (P < 10-5) and controls (P < 10-4),
      respectively, NT2 cases were not significantly different from controls (P = .64).
      Medication use (P = .009) but not adult versus children status (P = .85)
      significantly decreased the likelihood of a repeat positive MSLT. CONCLUSIONS: In
      a clinical setting, a positive MSLT for narcolepsy is a more reproducible and
      stable feature in NT1 than NT2. The retrospective design of this study hinders
      interpretation of these data, as there are many different, and possibly opposing,
      reasons to repeat a MSLT in NT1 versus NT2 (ie, ascertainment bias). Additional
      systematic MSLT repeatability studies independent of confounds are ideally needed
      to confirm these findings.

PMID- 29198302
TI  - Obstructive Sleep Apnea in Gestational Diabetes: A Pilot Study of the Role of the
      Hypothalamic-Pituitary-Adrenal Axis.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in pregnancy is associated with
      gestational diabetes mellitus (GDM). This propensity toward heightened insulin
      resistance in OSA patients has not been well characterized and may be related to
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this
      study was to (1) assess the prevalence of OSA in pregnant women with GDM, (2)
      evaluate whether HPA axis dysregulation relates to OSA, and (3) investigate the
      relation between insulin resistance and OSA. We hypothesized that OSA is
      prevalent among pregnant women with GDM and that women with OSA will have higher
      levels of insulin resistance and dysregulation of the HPA axis. METHODS: Twenty
      five pregnant women in whom GDM was diagnosed were enrolled. Subjects answered
      sleep questionnaires and underwent in-home sleep studies using a level III
      device. The presence of OSA was defined by apnea-hypopnea index >= 5 events/h.
      Homeostasis Model Assessment of insulin resistance was derived from measurements
      of fasting glucose and C-peptide levels. Three salivary cortisol levels were
      obtained across 1 day to assess circadian variation. Multivariable linear
      regression analyses were used to assess associations between variables. RESULTS:
      The sample consisted of 54% Caucasian pregnant women with a median body mass
      index of 36.1 and interquartile ratio of 10.6 kg/m2. OSA was diagnosed in 17% of
      participants. Circadian variation of cortisol was preserved in women with OSA.
      Women with OSA displayed blunted cortisol awakening responses. CONCLUSIONS: OSA
      is prevalent in women with GDM. OSA is associated with preserved circadian
      variation and blunted cortisol awakening responses.

PMID- 29198303
TI  - Predictors of Side Effects With Long-Term Oral Appliance Therapy for Obstructive
      Sleep Apnea.
AB  - STUDY OBJECTIVES: The aim of this study was to investigate the predictors of
      dental changes associated with long-term treatment with oral appliances (OAs) in
      patients with obstructive sleep apnea (OSA). METHODS: This was a retrospective
      study to investigate Japanese patients with OSA receiving long-term treatment
      with OAs. Comparisons of cephalometric analysis were carried out between the
      initial and follow-up assessments of dental and skeletal changes. Based on dental
      changes, predictors that may cause side effects were investigated. RESULTS: A
      total of 64 patients (average age at start of treatment: 57.7 +/- 14.2 years, 44
      males) were included in this study. The average duration of treatment was 4.3 +/-
      2.1 years. Over the total treatment period, there was a significant reduction in
      overjet (OJ) (1.5 +/- 1.3 mm) and overbite (0.90 +/- 1.5 mm), and an increase in
      the lower incisor line to the mandibular plane (3.1 +/- 5.4 degrees ). A larger
      reduction in OJ of >= 1 mm was associated with treatment duration, use frequency,
      and mandibular advancement of the OAs. In addition to these predictive factors,
      the number of teeth was correlated with the amount of OJ reduction. CONCLUSIONS:
      For long-term treatment with OAs, the risk of dental side effects should be
      considered, such as a reduction in OJ. A small number of maxillary teeth, as well
      as the factors associated with OAs, including treatment duration, use frequency,
      and mandibular advancement of the OAs, was correlated with an increased rate of
      OJ reduction. COMMENTARY: A commentary on this article appears in this issue on
      page 7.

PMID- 29198304
TI  - Neurobehavioral Impairment and CPAP Treatment Response in Mild-Moderate
      Obstructive Sleep Apneas.
AB  - STUDY OBJECTIVES: The degree of neurobehavioral impairment and treatment response
      in mild-moderate obstructive sleep apnea (OSA) compared to that of an appropriate
      control group are unclear. This study compared neurobehavioral function and
      response to continuous positive airway pressure (CPAP) treatment in patients with
      mild to moderate OSA with those of a non-sleep apneic community sample of similar
      demography. METHODS: One hundred ten patients with OSA and 31 asymptomatic
      community dwellers underwent overnight polysomnography and neurobehavioral
      testing. Participants with OSA (n = 88) were treated with CPAP for 3 months, and
      repeat evaluations were performed at the end of the treatment period. RESULTS:
      Compared to the community sample, participants with OSA were significantly
      sleepier, had impaired mood and quality of life, and showed decrements in
      neuropsychological function, specifically psychomotor function, working memory
      and vigilance. Some neuropsychological and mood outcomes were normalized with
      CPAP, but significant decrements persisted in most outcomes even in those
      participants with adequate device usage. CONCLUSIONS: Patients with mild to
      moderate OSA have significant neurobehavioral morbidity. During "gold standard"
      treatment, normal function was not achieved, even with adequate device usage.
      CPAP efficacy for improving sleepiness and neuropsychological function in this
      milder end of the OSA spectrum may be poor, which may affect CPAP adherence.
      These findings suggest that there may be neurological changes related to OSA that
      do not respond to CPAP treatment, the etiology of which requires further
      investigation.

PMID- 29198305
TI  - Comparing the Efficacy, Mask Leak, Patient Adherence, and Patient Preference of
      Three Different CPAP Interfaces to Treat Moderate-Severe Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: To determine if the type of continuous positive airway pressure
      (CPAP) mask interface influences CPAP treatment efficacy, adherence, side
      effects, comfort and sleep quality in patients with moderate-severe obstructive
      sleep apnea (OSA). METHODS: This took place in a hospital-based tertiary sleep
      disorders unit. It is a prospective, randomized, crossover trial comparing three
      CPAP interfaces: nasal mask (NM), nasal mask plus chinstrap (NM-CS) and oronasal
      mask (ONM) each tried in random order, for 4 weeks. After each 4-week period,
      patient outcomes were assessed. Participants had a new diagnosis of obstructive
      sleep apneas. Forty-eight patients with moderate-severe OSA (32 males, mean +/-
      standard deviation apnea-hypopnea index (AHI) 55.6 +/- 21.1 events/h, age 54.9 +/
      13.1 years, body mass index 35.8 +/- 7.2 kg/m2) were randomized. Thirty-five
      participants completed the full study, with complete data available for 34
      patients. RESULTS: There was no statistically significant difference in CPAP
      adherence; however, residual AHI was higher with ONM than NM and NM-CS (residual
      AHI 7.1 +/- 7.7, 4.0 +/- 3.1, 4.2 +/- 3.7 events/h respectively, main effect P =
      .001). Patient satisfaction and quality of sleep were higher with the NM and NM
      CS than the ONM. Fewer leak and mask fit problems were reported with NM (all chi
      square P < .05), which patients preferred over the NM-CS and ONM options (n = 22,
      9 and 4 respectively, P = .001). CONCLUSIONS: The CPAP adherence did not differ
      between the three different mask interfaces but the residual AHI was lower with
      NM than ONM and patients reported greater mask comfort, better sleep, and overall
      preference for a NM. A nasal mask with or without chinstrap should be the first
      choice for patients with OSA referred for CPAP treatment. CLINICAL TRIAL
      REGISTRATION: Registry: Australian and New Zealand Clinical Trials Registry, URL:
      https://www.anzctr.org.au, title: A comparison of continuous positive airway
      pressure (CPAP) interface in the control of leak, patient compliance and patient
      preference: nasal CPAP mask and chinstrap versus full face mask in patients with
      obstructive sleep apnoea (OSA), identifier: ACTRN12609000029291.

PMID- 29198306
TI  - Sleep Architecture in Children With Common Phenotype of Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: In children, the effect of the common phenotype of obstructive
      sleep apnea (OSA) on sleep architecture is not adequately documented. The aim of
      this study was to evaluate sleep architecture in a pediatric population with the
      common phenotype of OSA. METHODS: The prospective cross-sectional study included
      116 children in the age range of 3 to 8 years with suspected OSA and 51 healthy
      children. All children underwent standard overnight in-laboratory video
      polysomnography. Patients with obstructive apnea-hypopnea index >= 1,
      adenotonsillar hypertrophy, a long face, narrow palate or minor malocclusions,
      and no obesity were defined as a common phenotype. Polysomnographic parameters of
      sleep architecture and sleep clinical record were statistically analyzed
      according to OSA and its severity. RESULTS: In total, 94 pediatric patients
      (59.60% male) received the diagnosis of the common phenotype of OSA (mean age of
      5.25 +/- 1.39 years). A lower percentage of stage N3 sleep (27.70 +/- 3.76%
      versus 31.02 +/- 4.23%; P < .05), a greater percentage of stage N1 sleep (8.40 +/
      3.98% versus 2.68 +/- 3.02%, P < .01), reduced deep sleep efficiency (46.01 +/-
      4.98% versus 50.25 +/- 3.72%; P < .05) and longer sleep latency (18.40 +/- 8.48
      minutes versus 9.90 +/- 11.55 minutes, P < .01) were found in children with the
      common phenotype of OSA compared with healthy controls. No significant
      differences were found in total sleep time, sleep efficiency, and percentage of
      stage R sleep and stage N2 sleep between groups and in sleep stage distribution
      and cyclization. CONCLUSIONS: These findings suggest that the most common
      phenotype of pediatric OSA has a negative effect on the structure of sleep, but
      other clinical studies are needed to confirm this result.

PMID- 29198307
TI  - A bioequivalence study of quetiapine 25 mg film-coated tablets in healthy
      Indonesian subjects?.
AB  - AIM: This study was conducted in order to compare the bioavailability of two film
      coated tablets containing 25 mg of quetiapine. METHODS: 24 subjects were enrolled
      in and completed a single-center, randomized, single-dose, open-label, two-way
      crossover study with a 1-week washout period. Plasma samples were collected up to
      24 hours following drug administration; thus, quetiapine was determined by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method with turbo-ion-spray
      mode. The pharmacokinetic parameters used for bioequivalence assessment were
      AUC<sub>0-t</sub>, AUC<sub>0-infinity</sub>, and C<sub>max</sub>. The 90%
      confidence intervals were obtained by analysis of variance for AUC<sub>0-t,</sub>
      AUC<sub>0-infinity</sub>, and C<sub>max</sub>. RESULTS: The results were all
      within the range of 80.00 - 125.00%. CONCLUSION: Bioequivalence between
      formulations was concluded both in terms of rate and extent of absorption.?.

PMID- 29198308
TI  - Payload hardware and experimental protocol development to enable future testing
      of the effect of space microgravity on the resistance to gentamicin of
      uropathogenic Escherichia coli and its sigmas-deficient mutant.
AB  - Human immune response is compromised and bacteria can become more antibiotic
      resistant in space microgravity (MG). We report that under low-shear modeled
      microgravity (LSMMG), stationary-phase uropathogenic Escherichia coli (UPEC)
      become more resistant to gentamicin (Gm), and that this increase is dependent on
      the presence of sigmas (a transcription regulator encoded by the rpoS gene). UPEC
      causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a
      standard treatment, so these findings could impact astronaut health. Because
      LSMMG findings can differ from MG, we report preparations to examine UPEC's Gm
      sensitivity during spaceflight using the E. coli Anti-Microbial Satellite
      (EcAMSat) as a free-flying "nanosatellite" in low Earth orbit. Within EcAMSat's
      payload, a 48-microwell fluidic card contains and supports study of bacterial
      cultures at constant temperature; optical absorbance changes in cell suspensions
      are made at three wavelengths for each microwell and a fluid-delivery system
      provides growth medium and predefined Gm concentrations. Performance
      characterization is reported here for spaceflight prototypes of this payload
      system. Using conventional microtiter plates, we show that Alamar Blue (AB)
      absorbance changes can assess the Gm effect on E. coli viability, permitting
      telemetric transfer of the spaceflight data to Earth. Laboratory results using
      payload prototypes are consistent with wellplate and flask findings of
      differential sensitivity of UPEC and its ?rpoS strain to Gm. if sigmas plays the
      same role in space MG as in LSMMG and Earth gravity, countermeasures discovered
      in recent Earth studies (aimed at weakening the UPEC antioxidant defense) to
      control UPEC infections would prove useful also in space flights. Further,
      EcAMSat results should clarify inconsistencies from previous space experiments on
      bacterial antibiotic sensitivity and other issues.

PMID- 29198309
TI  - Effects of simulated microgravity on gene expression and biological phenotypes of
      a single generation Caenorhabditis elegans cultured on 2 different media.
AB  - Studies of multigenerational Caenorhabditis elegans exposed to long-term
      spaceflight have revealed expression changes of genes involved in longevity, DNA
      repair, and locomotion. However, results from spaceflight experiments are
      difficult to reproduce as space missions are costly and opportunities are rather
      limited for researchers. In addition, multigenerational cultures of C. elegans
      used in previous studies contribute to mixture of gene expression profiles from
      both larvae and adult worms, which were recently reported to be different. Usage
      of different culture media during microgravity simulation experiments might also
      give rise to differences in the gene expression and biological phenotypes of the
      worms. In this study, we investigated the effects of simulated microgravity on
      the gene expression and biological phenotype profiles of a single generation of
      C. elegans worms cultured on 2 different culture media. A desktop Random
      Positioning Machine (RPM) was used to simulate microgravity on the worms for
      approximately 52 to 54 h. Gene expression profile was analysed using the
      Affymetrix GeneChip(r) C. elegans 1.0 ST Array. Only one gene (R01H2.2) was found
      to be downregulated in nematode growth medium (NGM)-cultured worms exposed to
      simulated microgravity. On the other hand, eight genes were differentially
      expressed for C. elegans Maintenance Medium (CeMM)-cultured worms in
      microgravity; six were upregulated, while two were downregulated. Five of the
      upregulated genes (C07E3.15, C34H3.21, C32D5.16, F35H8.9 and C34F11.17) encode
      non-coding RNAs. In terms of biological phenotype, we observed that microgravity
      simulated worms experienced minimal changes in terms of lifespan, locomotion and
      reproductive capabilities in comparison with the ground controls. Taking it all
      together, simulated microgravity on a single generation of C. elegans did not
      confer major changes to their gene expression and biological phenotype.
      Nevertheless, exposure of the worms to microgravity lead to higher expression of
      non-coding RNA genes, which may play an epigenetic role in the worms during
      longer terms of microgravity exposure.

PMID- 29198310
TI  - Whole high-quality light environment for humans and plants.
AB  - Plants sharing a single light environment on a spaceship with a human being and
      bearing a decorative function should look as natural and attractive as possible.
      And consequently they can be illuminated only with white light with a high color
      rendering index. Can lighting optimized for a human eye be effective and
      appropriate for plants? Spectrum-based effects have been compared under
      artificial lighting of plants by high-pressure sodium lamps and general-purpose
      white LEDs. It has been shown that for the survey sample phytochrome photo
      equilibria does not depend significantly on the parameters of white LED light,
      while the share of phytoactive blue light grows significantly as the color
      temperature increases. It has been revealed that yield photon flux is
      proportional to luminous efficacy and increases as the color temperature
      decreases, general color rendering index Ra and the special color rendering index
      R14 (green leaf) increase. General-purpose white LED lamps with a color
      temperature of 2700 K, Ra > 90 and luminous efficacy of 100 lm/W are as efficient
      as the best high-pressure sodium lamps, and at a higher luminous efficacy their
      yield photon flux per joule is even bigger in proportion. Here we show that
      demand for high color rendering white LED light is not contradictory to the agro
      technical objectives.

PMID- 29198311
TI  - Comparison of methods for individualized astronaut organ dosimetry: Morphometry
      based phantom library versus body contour autoscaling of a reference phantom.
AB  - One of the hazards faced by space crew members in low-Earth orbit or in deep
      space is exposure to ionizing radiation. It has been shown previously that while
      differences in organ-specific and whole-body risk estimates due to body size
      variations are small for highly-penetrating galactic cosmic rays, large
      differences in these quantities can result from exposure to shorter-range trapped
      proton or solar particle event radiations. For this reason, it is desirable to
      use morphometrically accurate computational phantoms representing each astronaut
      for a risk analysis, especially in the case of a solar particle event. An
      algorithm was developed to automatically sculpt and scale the UF adult male and
      adult female hybrid reference phantom to the individual outer body contour of a
      given astronaut. This process begins with the creation of a laser-measured
      polygon mesh model of the astronaut's body contour. Using the auto-scaling
      program and selecting several anatomical landmarks, the UF adult male or female
      phantom is adjusted to match the laser-measured outer body contour of the
      astronaut. A dosimetry comparison study was conducted to compare the organ dose
      accuracy of both the autoscaled phantom and that based upon a height-weight
      matched phantom from the UF/NCI Computational Phantom Library. Monte Carlo
      methods were used to simulate the environment of the August 1972 and February
      1956 solar particle events. Using a series of individual-specific voxel phantoms
      as a local benchmark standard, autoscaled phantom organ dose estimates were shown
      to provide a 1% and 10% improvement in organ dose accuracy for a population of
      females and males, respectively, as compared to organ doses derived from height
      weight matched phantoms from the UF/NCI Computational Phantom Library. In
      addition, this slight improvement in organ dose accuracy from the autoscaled
      phantoms is accompanied by reduced computer storage requirements and a more rapid
      method for individualized phantom generation when compared to the UF/NCI
      Computational Phantom Library.

PMID- 29198312
TI  - Coupling of anaerobic waste treatment to produce protein- and lipid-rich
      bacterial biomass.
AB  - Future long-term manned space missions will require effective recycling of water
      and nutrients as part of a life support system. Biological waste treatment is
      less energy intensive than physicochemical treatment methods, yet anaerobic
      methanogenic waste treatment has been largely avoided due to slow treatment rates
      and safety issues concerning methane production. However, methane is generated
      during atmosphere regeneration on the ISS. Here we propose waste treatment via
      anaerobic digestion followed by methanotrophic growth of Methylococcus capsulatus
      to produce a protein- and lipid-rich biomass that can be directly consumed, or
      used to produce other high-protein food sources such as fish. To achieve more
      rapid methanogenic waste treatment, we built and tested a fixed-film, flow
      through, anaerobic reactor to treat an ersatz wastewater. During steady-state
      operation, the reactor achieved a 97% chemical oxygen demand (COD) removal rate
      with an organic loading rate of 1740 g d-1 m-3 and a hydraulic retention time of
      12.25 d. The reactor was also tested on three occasions by feeding ca. 500 g COD
      in less than 12 h, representing 50x the daily feeding rate, with COD removal
      rates ranging from 56-70%, demonstrating the ability of the reactor to respond to
      overfeeding events. While investigating the storage of treated reactor effluent
      at a pH of 12, we isolated a strain of Halomonas desiderata capable of acetate
      degradation under high pH conditions. We then tested the nutritional content of
      the alkaliphilic Halomonas desiderata strain, as well as the thermophile Thermus
      aquaticus, as supplemental protein and lipid sources that grow in conditions that
      should preclude pathogens. The M. capsulatus biomass consisted of 52% protein and
      36% lipids, the H. desiderata biomass consisted of 15% protein and 7% lipids, and
      the Thermus aquaticus biomass consisted of 61% protein and 16% lipids. This work
      demonstrates the feasibility of rapid waste treatment in a compact reactor
      design, and proposes recycling of nutrients back into foodstuffs via
      heterotrophic (including methanotrophic, acetotrophic, and thermophilic)
      microbial growth.

PMID- 29198313
TI  - Modifiers of radiation effects in the eye.
AB  - World events, including the threat of radiological terrorism and the fear of
      nuclear accidents, have highlighted an urgent need to develop medical
      countermeasures to prevent or reduce radiation injury. Similarly, plans for
      manned spaceflight to a near-Earth asteroid or journey to Mars raise serious
      concerns about long-term effects of space radiation on human health and the
      availability of suitable therapeutic interventions. At the same time, the need to
      protect normal tissue from the deleterious effects of radiotherapy has driven
      considerable research into the design of effective radioprotectors. For more than
      70 years, animal models of radiation cataract have been utilized to test the
      short and long-term efficacy of various radiation countermeasures. While some
      compounds, most notably the Walter Reed (WR) class of radioprotectors, have
      reported limited effectiveness when given before exposure to low-LET radiation,
      the human toxicity of these molecules at effective doses limits their usefulness.
      Furthermore, while there has been considerable testing of eye responses to X- and
      gamma irradiation, there is limited information about using such models to limit
      the injurious effects of heavy ions and neutrons on eye tissue. A new class of
      radioprotector molecules, including the sulfhydryl compound PrC-210, are reported
      to be effective at much lower doses and with far less side effects. Their ability
      to modify ocular radiation damage has not yet been examined. The ability to non
      invasively measure sensitive, radiation-induced ocular changes over long periods
      of time makes eye models an attractive option to test the radioprotective and
      radiation mitigating abilities of new novel compounds.

PMID- 29198314
TI  - T cell resistance to activation by dendritic cells requires long-term culture in
      simulated microgravity.
AB  - Immune impairment mediated by microgravity threatens the success of space
      exploration requiring long-duration spaceflight. The cells of most concern, T
      lymphocytes, coordinate the host response against microbial and cancerous
      challenges leading to elimination and long-term protection. T cells are activated
      upon recognition of specific microbial peptides bound on the surface of antigen
      presenting cells, such as dendritic cells (DC). Subsequently, this engagement
      results in T cell proliferation and differentiation into effector T cells driven
      by autocrine interleukin-2 (IL-2) and other cytokines. Finally, the effector T
      cells acquire the weaponry needed to destroy microbial invaders and tumors.
      Studies conducted on T cells during spaceflight, or using Earth-based culture
      systems, have shown reduced production of cytokines, proliferation and effector
      functions as compared to controls. This may account for the cases of viral
      reactivation events and opportunistic infections associated with astronauts of
      numerous missions. This work has largely been based upon the outcome of T cell
      activation by stimulatory factors that target select T cell signaling pathways
      rather than the complex, signaling events related to the natural process of
      antigen presentation by DC. This study tested the response of an ovalbumin
      peptide-specific T cell line, OT-II TCH, to activation by DC when the T cells
      were cultured 24-120 h in a simulated microgravity (SMG) environment generated by
      a rotary cell culture system. Following 72 h culture of T cells in SMG (SMG-T) or
      control static (Static-T) conditions, IL-2 production by the T cells was reduced
      in SMG-T cells compared to Static-T cells upon stimulation by phorbol 12
      myristate 13-acetate (PMA) and ionomycin. However, when the SMG-T cells were
      stimulated with DC and peptide, IL-2 was significantly increased compared to
      Static-T cells. Such enhanced IL-2 production by SMG-T cells peaked at 72 h SMG
      culture time and decreased thereafter. When activation of SMG-T cells occurred in
      SMG, the T cells produced less IL-2 than control T cell cultures upon incubation
      with PMA and ionomycin. Short-term (24 h) SMG culture and activation of T cells
      by DC resulted in enhanced IL-2 production compared to Static-T cells, however,
      when culture was extended to 120 h, SMG-T cells secreted significantly less IL-2
      than Static-T cells. SMG-T cell IL-2 doubled upon stimulation of the DC prior to
      addition to the T cell culture but remained less than control. SMG-T cell
      resistance to activation appeared comparable to the phenomenon of T cell
      exhaustion observed in patients with chronic diseases or persistent tumors. That
      is, long-term culture of T cells in SMG resulted in increased expression of the
      inhibitory receptor, CTLA-4. Blockade of CTLA-4 interaction with DC ligands
      resulted in improved T cell IL-2 production. Overall, this is the first study to
      determine the efficacy of DC in activating peptide-specific T cells. Furthermore,
      the findings suggests that countermeasures to restore T cell responsiveness in
      astronauts during long-term spaceflight or those living in microgravity
      environments should target possible inhibitory pathways that arise on activated T
      cells following stimulation.

PMID- 29198315
TI  - Mimicking the effects of spaceflight on bone: Combined effects of disuse and
      chronic low-dose rate radiation exposure on bone mass in mice.
AB  - During spaceflight, crewmembers are subjected to biomechanical and biological
      challenges including microgravity and radiation. In the skeleton, spaceflight
      leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb
      suspension (HLS) as a ground-based model of spaceflight often neglect the
      concomitant effects of radiation exposure, and even when radiation is accounted
      for, it is often delivered at a high-dose rate over a very short period of time,
      which does not faithfully mimic spaceflight conditions. This study was designed
      to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy
      gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when
      administered simultaneously to disuse from HLS. The goal was to determine whether
      continuous, low-dose rate radiation administered during disuse would exacerbate
      bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice
      were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation
      exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and
      trabecular bone loss, concurrent radiation exposure did not exacerbate these
      effects. Our results raise the possibility that mechanical unloading has larger
      effects on the bone loss that occurs during spaceflight than low-dose rate
      radiation.

PMID- 29198316
TI  - Exploring innovative radiation shielding approaches in space: A material and
      design study for a wearable radiation protection spacesuit.
AB  - We present a design study for a wearable radiation-shielding spacesuit, designed
      to protect astronauts' most radiosensitive organs. The suit could be used in an
      emergency, to perform necessary interventions outside a radiation shelter in the
      space habitat in case of a Solar Proton Event (SPE). A wearable shielding system
      of the kind we propose has the potential to prevent the onset of acute radiation
      effects in this scenario. In this work, selection of materials for the spacesuit
      elements is performed based on the results of dedicated GRAS/Geant4 1-dimensional
      Monte Carlo simulations, and after a trade-off analysis between shielding
      performance and availability of resources in the space habitat. Water is the
      first choice material, but also organic compounds compatible with a human space
      habitat are considered (such as fatty acids, gels and liquid organic wastes).
      Different designs and material combinations are proposed for the spacesuits. To
      quantify shielding performance we use GRAS/Geant4 simulations of an
      anthropomorphic phantom in an average SPE environment, with and without the
      spacesuit, and we compare results for the dose to Blood Forming Organs (BFO) in
      Gy-Eq, i.e. physical absorbed dose multiplied by the proton Relative Biological
      Effectiveness (RBE) for non-cancer effects. In case of SPE occurrence for Intra
      Vehicular Activities (IVA) outside a radiation shelter, dose reductions to BFO in
      the range of 44-57% are demonstrated to be achievable with the spacesuit designs
      made only of water elements, or of multi-layer protection elements (with a thin
      layer of a high density material covering the water filled volume). Suit elements
      have a thickness in the range 2-6 cm and the total mass for the garment sums up
      to 35-43 kg depending on model and material combination. Dose reduction is
      converted into time gain, i.e. the increase of time interval between the
      occurrence of a SPE and the moment the dose limit to the BFO for acute effects is
      reached. Wearing a radiation shielding spacesuit of the kind we propose, the
      astronaut could have up to more than the double the time (e.g. almost 6 instead
      of 2.5 h) to perform necessary interventions outside a radiation shelter during a
      SPE, his/her exposure remaining within dose limits. An indicative mass saving
      thanks to the shielding provided by the suits is also derived, calculating the
      amount of mass needed in addition to the 1.5 cm thick Al module considered for
      the IVA scenario to provide the same additional shielding given by the spacesuit.
      For an average 50% dose reduction to BFO this is equal to about 2.5 tons of Al.
      Overall, our results offer a proof-of-principle validation of a complementary
      personal shielding strategy in emergency situations in case of a SPE event. Such
      results pave the way for the design and realization of a prototype of a water
      filled garment to be tested on board the International Space Station for
      wearability. A successful outcome will possibly lead to the further refining of
      the design of radiation protection spacesuits and their possible adoption in
      future long-duration manned missions in deep space.

PMID- 29198317
TI  - Effects of high-intensity static magnetic fields on a root-based bioreactor
      system for space applications.
AB  - Static magnetic fields created by superconducting magnets have been proposed as
      an effective solution to protect spacecrafts and planetary stations from cosmic
      radiations. This shield can deflect high-energy particles exerting injurious
      effects on living organisms, including plants. In fact, plant systems are
      becoming increasingly interesting for space adaptation studies, being useful not
      only as food source but also as sink of bioactive molecules in future
      bioregenerative life-support systems (BLSS). However, the application of
      protective magnetic shields would generate inside space habitats residual
      magnetic fields, of the order of few hundreds milli Tesla, whose effect on plant
      systems is poorly known. To simulate the exposure conditions of these residual
      magnetic fields in shielded environment, devices generating high-intensity static
      magnetic field (SMF) were comparatively evaluated in blind exposure experiments
      (250 mT, 500 mT and sham -no SMF-). The effects of these SMFs were assayed on
      tomato cultures (hairy roots) previously engineered to produce anthocyanins,
      known for their anti-oxidant properties and possibly useful in the setting of
      BLSS. Hairy roots exposed for periods ranging from 24 h to 11 days were
      morphometrically analyzed to measure their growth and corresponding molecular
      changes were assessed by a differential proteomic approach. After disclosing
      blind exposure protocol, a stringent statistical elaboration revealed the absence
      of significant differences in the soluble proteome, perfectly matching phenotypic
      results. These experimental evidences demonstrate that the identified plant
      system well tolerates the exposure to these magnetic fields. Results hereby
      described reinforce the notion of using this plant organ culture as a tool in
      ground-based experiments simulating space and planetary environments, in a
      perspective of using tomato 'hairy root' cultures as bioreactor of ready-to-use
      bioactive molecules during future long-term space missions.

PMID- 29198318
TI  - Growth in spaceflight hardware results in alterations to the transcriptome and
      proteome.
AB  - The Biological Research in Canisters (BRIC) hardware has been used to house many
      biology experiments on both the Space Transport System (STS, commonly known as
      the space shuttle) and the International Space Station (ISS). However,
      microscopic examination of Arabidopsis seedlings by Johnson et al. (2015)
      indicated the hardware itself may affect cell morphology. The experiment herein
      was designed to assess the effects of the BRIC-Petri Dish Fixation Units (BRIC
      PDFU) hardware on the transcriptome and proteome of Arabidopsis seedlings. To our
      knowledge, this is the first transcriptomic and proteomic comparison of
      Arabidopsis seedlings grown with and without hardware. Arabidopsis thaliana wild
      type Columbia (Col-0) seeds were sterilized and bulk plated on forty-four 60 mm
      Petri plates, of which 22 were integrated into the BRIC-PDFU hardware and 22 were
      maintained in closed containers at Ohio University. Seedlings were grown for
      approximately 3 days, fixed with RNAlater(r) and stored at -80  degrees C prior
      to RNA and protein extraction, with proteins separated into membrane and soluble
      fractions prior to analysis. The RNAseq analysis identified 1651 differentially
      expressed genes; MS/MS analysis identified 598 soluble and 589 membrane proteins
      differentially abundant both at p < .05. Fold enrichment analysis of gene
      ontology terms related to differentially expressed transcripts and proteins
      highlighted a variety of stress responses. Some of these genes and proteins have
      been previously identified in spaceflight experiments, indicating that these
      genes and proteins may be perturbed by both conditions.

PMID- 29198319
TI  - A Technique for Tripartite Reconstruction of Fingertip Injuries Using the Thenar
      Flap With Bone and Nail Bed Grafts.
AB  - Fingertip amputation is the most common amputation encountered by hand surgeons.
      Treatment decisions are multifactorial, based on mechanism, level of injury,
      tissue loss, associated injuries, and patient preference, among others. In this
      article, we present use of the thenar flap in combination with bone graft and
      split-thickness nail bed graft to address the tripartite loss of distal phalanx,
      soft tissue, and nail bed. This method allows for a full-length and functional
      reconstructed fingertip that is aesthetically satisfactory and does not require
      microsurgical techniques.

PMID- 29198320
TI  - ASSH Presidential Address: Engagement and Our Professional Responsibility.

PMID- 29198321
TI  - Perivitelline threads: an overlooked feature of cleavage-stage human embryos or
      an epiphenomenon in search of a function?

PMID- 29198322
TI  - TERT promoter mutation and its interaction with IDH mutations in glioma: Combined
      TERT promoter and IDH mutations stratifies lower-grade glioma into distinct
      survival subgroups-A meta-analysis of aggregate data.
AB  - The clinical significance of telomerase reverse transcriptase (TERT) promoter
      mutation in glioma remains unclear. The aim of our meta-analysis is to
      investigate the prognostic impact TERT promoter mutation in glioma patients and
      its interaction with other molecular markers, particularly Isocitrate
      Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were
      searched in four electronic databases including PubMed, Scopus, Web of Science
      and Virtual Health Library. Pooled HRs were calculated using random effect model
      weighted by inverse variance method. From 1010 studies, we finally included 28
      studies with 11519 patients for meta-analyses. TERT mutation is significantly
      associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and
      progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients.
      In studying its reaction with IDH, TERT promoter mutation was associated with
      reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas
      but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our
      analysis categorized WHO grade II/III glioma patients into four distinct survival
      subgroups with descending survival as follow: TERT-mut/IDH-mut?TERT-wt/IDH
      mut?TERT-wt/IDH-wt?TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations
      in gliomas is dependent on tumor grade and the IDH mutational status. With the
      same tumor grade in WHO grade II and III tumors and the same IDH mutation status,
      TERT-mut is a prognostic factor.

PMID- 29198323
TI  - Erratum to "Cancer-related Fatigue in Adolescents and Young Adults: A Systematic
      Review of the Literature" [Crit. Rev. Oncol. Hematol. 118 (2017) 63-69].

PMID- 29198324
TI  - Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG).
AB  - Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median
      survival of 10 months after radiation. At present, chemotherapy has failed to
      show benefits over radiation. Advances in biotechnology have enabled the use of
      autopsy specimens for genomic analyses and molecular profiling of DIPG, which are
      quite different from those of supratentorial high grade glioma. Recently,
      combined treatments of cytotoxic agents with target inhibitors, based on biopsied
      tissue, are being examined in on-going trials. Spontaneous DIPG mice models have
      been recently developed that is useful for preclinical studies. Finally, the
      convection-enhanced delivery could be used to infuse drugs directly into the
      brainstem parenchyma, to which conventional systemic administration fails to
      achieve effective concentration. The WHO glioma classification defines a diffuse
      midline glioma with a H3-K27M-mutation, and we expect increase of tissue
      confirmation of DIPG, which will give us the biological information helping the
      development of a targeted therapy.

PMID- 29198325
TI  - ERCC1 as a prognostic factor for survival in patients with advanced urothelial
      cancer treated with platinum based chemotherapy: A systematic review and meta
      analysis.
AB  - BACKGROUND: The predictive role of excision repair cross-complementing group 1
      (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC)
      treated with platinum-based treatment is not well defined. Here, we evaluate the
      role of ERCC1 in patients with AUC treated with platinum-based treatment.
      METHODS: We performed comprehensive, systematic computerized search to identify
      relevant studies through Medline, Embase, Cochrane Controlled Trials Register
      (CCTR) databases and abstracts from American Society of Clinical Oncology (ASCO)
      and ASCO Genitourinary Cancers Symposium, European Society For Medical Oncology
      (ESMO) and European Association of Urology (EAU) meeting up to July 2015. A
      systematic review and meta-analysis were performed. RESULTS: We included a total
      of 1475 patients from 13 studies. We found that ERCC1 positivity was
      significantly associated with worse progression-free survival (pooled HR: 1.54,
      95% CI: 1.13-2.11, p=0.006). There was no significant association with overall
      survival (pooled HR1.63, 95% CI: 0.93-2.88, p=0.09) and disease-free survival
      (pooled HR: 1.092, 95% CI: 0.63-1.90, p=0.75). CONCLUSION: ERCC1 positivity might
      be a prognostic indicator for poorer survival outcomes among patients with AUC.
      ERCC1 positivity was trending to poorer OS but was statistically worse for PFS.
      Further large prospective studies are warranted as ERCC1 could be used as a
      predictive marker to direct treatment of patients with AUC.

PMID- 29198326
TI  - The molecular genetics of chemotherapy-induced peripheral neuropathy: A
      systematic review and meta-analysis.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) can adversely affect completion
      of systemic anti-cancer treatment and cause long-term morbidity. Increasingly
      pharmacogenetic studies have been performed to explore susceptibility to this
      important adverse effect. A systematic review was conducted to identify
      pharmacogenetic studies, assess their quality and findings and undertake meta
      analysis where possible. 93 studies were included. Notable methodological issues
      included lack of standardisation and detail in phenotype definition and
      acknowledgement of potential confounding factors. Insufficient data was presented
      in many studies meaning only a minority could be included in meta-analysis
      showing mainly non-significant effects. Nonetheless, SNPs in CYP2C8, CYP3A4,
      ARHGEF10, EPHA and TUBB2A genes (taxanes), FARS2, ACYP2 and TAC1 (oxaliplatin),
      and CEP75 and CYP3A5 (vincristine) are of potential interest. These require
      exploration in large cohort studies with robust methodology and well-defined
      phenotypes. Seeking standardisation of phenotype, collaboration and subsequently,
      individual-patient-data meta-analysis may facilitate identifying contributory
      SNPs which could be combined in a polygenic risk score to predict those most at
      risk of CIPN.

PMID- 29198327
TI  - Critical features and challenges associated with imaging in patients undergoing
      cancer immunotherapy.
AB  - Manipulating an individual's immune system through immune checkpoint blockade is
      revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics
      of response have been observed with these new drugs, rendering the assessment of
      tumor burden particularly challenging in cancer immunotherapy. The mechanisms of
      action for immune checkpoint blockade, based upon engagement of the adaptive
      immune system, can generate unusual response patterns, including
      pseudoprogression, hyperprogression, atypical and delayed responses. In patients
      treated with immune checkpoint blockade and radiotherapy, a reduction in tumor
      burden at metastatic sites distant from the irradiation field (abscopal effect)
      has been observed, with synergistic systemic immune effects provoked by this
      combination. New toxicities have also been observed, due to excessive immune
      activity in several organs, including lung, colon, liver and endocrine glands.
      Efforts to standardize assessment of cancer immunotherapy responses include novel
      consensus guidelines derived by modifying World Health Organization (WHO) and
      Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The aim of this
      review is to evaluate imaging techniques currently used routinely in the clinic
      and those being used as investigational tools in immunotherapy clinical trials.

PMID- 29198328
TI  - The role of Nuclear Factor-kappa B signaling in human cervical cancer.
AB  - Background The Nuclear Factor kappaB (NF-kB) family consists of transcription
      factors that play a complex and essential role in the regulation of immune
      responses and inflammation. NF-kB has recently generated considerable interest as
      it has been implicated in human cancer initiation, progression and resistance to
      treatment. In the present comprehensive review the different aspects of NF-kB
      signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF
      kB functions as part of a network, which determines the pattern of its effects on
      the expression of several other genes (such as crosstalks with reactive oxygen
      species, p53, STAT3 and miRNAS) and thus its function. Activation of NF-kB
      triggered by a HPV infection is playing an important role in the innate and
      adaptive immune response of the host. The virus induces down regulation of NF-kB
      to liquidate the inhibitory activity for its replication triggered by the immune
      system leading a status of persistant HPV infection. During the progression to
      high grade intraepithelial neoplasia and cervical cancer NF-KB becomes
      constitutionally activated again. Mutations in NF-kB genes are rare in solid
      tumors but mutations of upstream signaling molecules such as RAS, EGFR, PGF, HER2
      have been implicated in elevated NF-kB signaling. NF-kB can stimulate
      transcription of proliferation regulating genes (eg. cyclin D1 and c-myc), genes
      involved in metastasis, VEGF dependent angiogenesis and cell immortality by
      telomerase. NF-kB activation can also induce the expression of activation-induced
      cytodine deaminase (AID) and the APOBEC proteins, providing a mechanistic link
      between the NF-kB pathway and mutagenic characteristic of cervical cancer.
      Inhibition of NF-kB has the potential to be used to reverse resistance to
      radiotherapy and systemic anti-cancer medication, but currently no clinicaly
      active NF-kB targeting strategies are available.

PMID- 29198329
TI  - Examining the bleeding incidences associated with targeted therapies used in
      metastatic renal cell carcinoma.
AB  - A systematic review was conducted to illustrate the bleeding risks associated
      with targeted therapies used in the treatment of metastatic renal cell carcinoma
      (mRCC). Eligible studies included phase II, III, or IV clinical trials using
      pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus,
      bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding
      event(s), bleeding event frequency, and incidence of thrombocytopenia were
      collected from the relevant articles. ClinicalTrials.gov was also searched for
      incidence of "Serious bleeding adverse effects" reported in these trials. The
      incidences of bleeding events ranged from 1 to 36%, and incidences of
      thrombocytopenia ranged from 2 to 78%. Available serious bleeding adverse events
      ranged from 1 to 7%. The highest percentage of bleeding incidences were seen with
      bevacizumab, while the lowest percentage of bleeding incidences were seen with
      axitinib. All of the included trials were of high quality per Jadad scoring.

PMID- 29198330
TI  - Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on
      cancer treatment outcomes: An overview about well-established and recently
      emerging clinical data.
AB  - Despite the overwhelming evidence for the role of granulocyte colony stimulating
      factors (G-CSF) in managing febrile neutropenia (FN) risk, chemotherapy-induced
      neutropenia (CIN) and/or FN still remain the most common reasons for reducing
      relative dose intensity (RDI) and/or delaying chemotherapy schedule. The need to
      maintain RDI to ensure optimal clinical outcomes is one of the key rationales for
      utilizing G-CSF. There is a high incidence of reduced RDI in both curative and
      palliative settings, and this observation is especially evidenced in
      retrospective analyses. Reduced RDI leads to significantly decreased survival
      outcomes and quality of life in various malignancies at various clinical settings
      and stages. Beyond its role as a surrogate prognostic marker, high-grade CIN may
      have an unexpected predictive role in clinical practice, as illustrated by
      several data relating CIN occurrence with favorable survival outcomes; this may
      be due to the fact that body surface area (BSA) - based calculation of dose may
      not fully account for the pharmacokinetics (PK) of cytotoxic drugs and the fact
      that there may be variability in drug metabolism between patients treated with
      same chemotherapy regimens.

PMID- 29198331
TI  - Biomarkers in prostate cancer - Current clinical utility and future perspectives.
AB  - Current tendencies in the treatment course of prostate cancer patients increase
      the need for reliable biomarkers that help in decision-making in a challenging
      clinical setting. Within the last decade, several novel biomarkers have been
      introduced. In the following comprehensive review article, we focus on diagnostic
      (PHI(r), 4K score, SelectMDx(r), ConfirmMDx(r), PCA3, MiPS, ExoDX(r), mpMRI) and
      prognostic (OncotypeDX GPS(r), Prolaris(r), ProMark(r), DNA-ploidy, Decipher(r))
      biomarkers that are in widespread clinical use and are supported by evidence.
      Hereby, we focus on multiple clinical situations in which innovative biomarkers
      may guide decision-making in prostate cancer therapy. In addition, we describe
      novel liquid biopsy approaches (circulating tumor cells, cell-free DNA) that have
      been described as predictive biomarkers in metastatic castration-resistant
      prostate cancer and might support an individual patient-centred oncological
      approach in the nearer future.

PMID- 29198332
TI  - Optimization and purification of l-asparaginase from fungi: A systematic review.
AB  - The purpose of this systematic review was to identify the available literature of
      the l-asparaginase producing fungi. This study followed the Preferred Reporting
      Items for Systematic Reviews. The search was conducted on five databases: LILACS,
      PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with
      no time or language restrictions. The reference list of the included studies was
      crosschecked and a partial gray literature search was undertaken. The methodology
      of the selected studies was evaluated using GRADE. Asparaginase production,
      optimization using statistical design, purification and characterization were the
      main evaluated outcomes. Of the 1686 initially gathered studies, 19 met the
      inclusion criteria after a two-step selection process. Nine species of fungi were
      reported in the selected studies, out of which 13 studies optimized the medium
      composition using statistical design for enhanced asparaginase production and six
      reported purification and characterization of the enzyme. The genera Aspergillus
      were identified as producers of asparaginase in both solid and submerged
      fermentation and l-asparagine was the amino acid most used as nitrogen source.
      This systematic review demonstrated that different fungi produce l-asparaginase,
      which possesses a potential in leukemia treatment. However, further
      investigations are required to confirm the promising effect of these fungal
      enzymes.

PMID- 29198333
TI  - The Therapeutic use of human albumin in cancer patients' management.
AB  - Human albumin (HA) has been widely used in clinical practice due to its unique
      physiological characteristics and pharmacokinetics. However, with the absence of
      clear institutional recommendations, its uncontrolled prescription remains
      largely controversial. An extensive review on the albumin chemistry,
      pharmacology, physiology and pathology was performed, and data on commercially
      available HA, its cost, medical usage and the related available guidelines,
      particularly in oncology patients were gathered. Studies assessing the
      appropriate use and safety of HA in cancer patients are lacking. A retrospective
      survey of the appropriateness of HA infusions according to the SIMTI guidelines
      (2009) was performed in our department. Among 53 patients who received HA
      infusions, only 5.7% of the indications were appropriate for HA administration.
      Occasionally appropriate and inappropriate indications were considered in 10% and
      84.3% of the prescriptions respectively with a relatively high cost. The adoption
      of strict guidelines may substantially reduce the inappropriate use and the
      subsequent healthcare costs.

PMID- 29198334
TI  - Mind and body practices for fatigue reduction in patients with cancer and
      hematopoietic stem cell transplant recipients: A systematic review and meta
      analysis.
AB  - PURPOSE: To determine whether non-physical activity mind and body practices
      reduce the severity of fatigue in patients with cancer or hematopoietic stem cell
      transplant (HSCT) recipients compared to control interventions. METHODS: We
      included randomized trials which compared non-physical activity mind and body
      practices compared with control interventions for the management of fatigue in
      cancer and HSCT patients. RESULTS: Among 55 trials (4975 patients), interventions
      were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques
      (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and
      others (n=8). When combined, all interventions significantly reduced fatigue
      severity compared to all controls (standardized mean difference -0.51, 95%
      confidence interval -0.73 to -0.29). More specifically, mindfulness and
      relaxation significantly reduced fatigue severity. CONCLUSIONS: Mindfulness and
      relaxation were effective at reducing fatigue severity in patients with cancer
      and HSCT recipients. Future studies should evaluate how to translate these
      findings into clinical practice across different patient groups.

PMID- 29198335
TI  - MicroRNAs in glioblastoma pathogenesis and therapy: A comprehensive review.
AB  - Glioblastoma (GBM), also known as grade IV astrocytoma, is the most aggressive
      primary intracranial tumor of the adult brain. MicroRNAs (miRNAs), a class of
      small non-coding RNA species, have critical functions across various biological
      processes. A great deal of progress has been made recently in dissecting miRNA
      pathways associated with the pathogenesis of GBM. miRNA expression signatures
      called gene signatures also characterize and contribute to the phenotypic
      diversity of GBM subclasses through their ability to regulate developmental
      growth and differentiation. miRNA molecules have been identified as diagnostic
      and prognostic biomarkers for patient stratification and may also serve as
      therapeutic targets and agents. This review summarizes: (i) the current
      understanding of the roles of miRNAs in the pathogenesis of GBM, (ii) the
      potential use of miRNAs in GBM diagnosis and glioma grading, (iii) further
      prospects of developing miRNAs as novel biomarkers and therapeutic targets for
      GBM, and (iv) important practical considerations when considering miRNA therapy
      for GBM patients.

PMID- 29198336
TI  - Fertility management for malignant ovarian germ cell tumors patients.
AB  - Malignant Germ Cell Tumors have primarily affecting adolescents and young adults.
      In advanced disease, greater than 70% of patients can be cured with standard
      chemotherapy regimens and fertility-sparing surgery appears to be safe with
      excellent survival after long-term follow-up. Due to their rarity, follow up and
      fertility management is largely based on trials of epithelial ovarian cancer or
      on few small studies. We report a review of the literature studies about the
      assessment, the monitoring and the treatment of fertility for Malignant Germ Cell
      Tumors as pratical guidelines for management of fertility in these patients.

PMID- 29198337
TI  - Ovarian sex-cord stromal tumours and small cell tumours: Pathological, genetic
      and management aspects.
AB  - Non-epithelial ovarian cancers (NEOC) constitute a group of uncommon malignancies
      and their treatment is still a challenging task. Collectively, these tumours
      account for about 10% of all ovarian cancers and occur in all age groups from
      childhood to old-age. They include malignancies of germ cell origin, sex cord
      stromal cell origin, and a variety of extremely rare ovarian cancers, such as
      small-cell carcinomas and sarcomas. Each of these classifications encompasses
      multiple histologic subtypes. It is imperative that these rare tumours are
      managed with accurate diagnosis, staging, and treatment, to optimise the outcome.
      The aetiology and molecular origins of each sub-group of NEOC remain largely
      unresolved, and international cooperation to promote high quality translational
      research is crucial. Much effort has been made into researching the molecular
      mechanisms underlying epithelial ovarian cancers, but far less is known about the
      genetic changes in NEOC. In this article, it is provided an overview of the
      current knowledge on the incidence, clinical presentation, pathology, genetics,
      therapeutic interventions, survival and prognostic factors of adult and juvenile
      granulosa cell tumours (GrCT), Sertoli-Leydig Cell tumours (SLCT) and small cell
      carcinoma of the ovary. We also consider future potential therapeutic targets in
      these rare cancers.

PMID- 29198338
TI  - Ponatinib in chronic myeloid leukemia (CML): Consensus on patient treatment and
      management from a European expert panel.
AB  - Five tyrosine kinase inhibitors (TKIs) are currently approved in the European
      Union for treatment of chronic myeloid leukemia (CML) and all have considerable
      overlap in their indications. While disease-specific factors such as CML phase,
      mutational status, and line of treatment are key to TKI selection, other
      important features must be considered, such as patient-specific comorbidities and
      TKI safety profiles. Ponatinib, the TKI most recently approved, has demonstrated
      efficacy in patients with refractory CML, but is associated with an increased
      risk of arterial hypertension, sometimes severe, and serious arterial occlusive
      and venous thromboembolic events. A panel of European experts convened to discuss
      their clinical experience in managing patients with CML. Based on the panel
      discussions, scenarios in which a CML patient may be an appropriate candidate for
      ponatinib therapy are described, including presence of the T315I mutation,
      resistance to other TKIs without the T315I mutation, and intolerance to other
      TKIs.

PMID- 29198339
TI  - Patterns and drivers of health care use in long-term childhood cancer survivors:
      A systematic review.
AB  - BACKGROUND: Childhood cancer survival is increasing. But cancer and treatment
      late-effects can lead to ongoing health care use. We summarised the literature on
      the patterns and drivers of health care use among childhood cancer survivors.
      METHOD: Pubmed, Embase and Medline were searched for studies reporting health
      care use in childhood cancer survivors. RESULTS: We included 22 studies, covering
      88787 experiences of health care use. The proportion of survivors using follow-up
      care, physician visits, specialist visits, hospitalisations, dental care and
      screening services varied (36.4%-88.8%). Participation in screening was below
      recommendations (11.5%-81%). Drivers of increased health care use included higher
      income, private health insurance, attending follow-up care, chronic health
      conditions, prior radiotherapy, being female and older age. CONCLUSION:
      Sociodemographic and clinical factors result in differences in health care use.
      Future research could investigate whether such use is appropriate and how
      survivors might be engaged to receive care appropriate to manage their needs.

PMID- 29198340
TI  - Emerging roles for long noncoding RNAs in B-cell development and malignancy.
AB  - Long noncoding (lnc)RNAs have emerged as essential mediators of cellular biology,
      differentiation and malignant transformation. LncRNAs have a broad range of
      possible functions at the transcriptional, posttranscriptional and protein level
      and their aberrant expression significantly contributes to the hallmarks of
      cancer cell biology. In addition, their high tissue- and cell-type specificity
      makes lncRNAs especially interesting as biomarkers, prognostic factors or
      specific therapeutic targets. Here, we review current knowledge on lncRNA
      expression changes during normal B-cell development, indicating essential
      functions in the differentiation process. In addition we address lncRNA
      deregulation in B-cell malignancies, the putative prognostic value of this as
      well as the molecular functions of multiple deregulated lncRNAs. Altogether, the
      discussed work indicates major roles for lncRNAs in normal and malignant B cells
      affecting oncogenic pathways as well as the response to common therapeutics.

PMID- 29198341
TI  - Concomitant use of corticosteroids and immune checkpoint inhibitors in patients
      with hematologic or solid neoplasms: A systematic review.
AB  - PURPOSE: Clinical trials studying immune checkpoint inhibitors exclude patients
      on corticosteroids, due to the hypothesis that corticosteroids may antagonize
      immunotherapy. We performed a systematic review of the literature looking at the
      clinical outcomes of cancer patients treated with immune checkpoint inhibitors
      and concomitant corticosteroids. METHODS: The following databases were searched
      for relevant studies: MEDLINE, Embase Classic+Embase, BIOSIS Previews, the
      Cochrane Database of Systematic Reviews, the CENTRAL Registry of Controlled
      Trials, Web of Science and Scopus. Abstracts from the meetings of the European
      Cancer Congress/European Society for Medical Oncology, the American Society of
      Clinical Oncology, the American Society of Hematology, the European Society for
      Radiotherapy & Oncology, the American Society for Radiation Oncology and the
      European Society for Radiotherapy & Oncology were manually searched. Two
      independent reviewers screened the references: case reports and articles with a
      low risk of bias were retained. RESULTS: Following a retrieval of 14603 unique
      references, 140 abstracts were retained for review; 27 articles are in the final
      analysis. Although limited, the reviewed data suggests that the concomitant
      administration of corticosteroids and immune checkpoint inhibitors may not
      necessarily lead to poorer clinical outcomes. CONCLUSION: In our systematic
      review, there was no objective data on the exact types of corticosteroids and the
      dose threshold above which an interaction could be measured clinically.
      Consideration of stratified randomization and treatment sequence evaluations in
      prospective trials may clarify this challenging topic and perhaps improve patient
      access to immune checkpoint therapies.

PMID- 29198342
TI  - Management of salivary gland malignant tumor: the Policlinico Umberto I,
      "Sapienza" University of Rome Head and Neck Unit clinical recommendations.
AB  - Salivary gland malignant tumor (SGMT) is a malignant disease requiring
      multidisciplinary approach. The rare incidence and the consequent lack of robust
      evidence-based medicine has called for a comprehensive update to draw
      recommendations for clinical practice. This paper is a summary of the XXX Head
      and Neck Unit guidelines regarding the management of SGMT. Recommendations
      include the indications for exclusive and adjuvant therapy, as well as metastatic
      management, for both major and minor SGMT.

PMID- 29198344
TI  - 2017: Alterum Annum Nobilis Arthroscopy (AANA).
AB  - In 2017, the Arthroscopy Association of North America (AANA) continues to be
      defined. Arthroscopy is an international journal and represents a worldwide
      Academic Association of Naturally-gifted Arthroscopists (AANA). When we look to
      the past to better understand the present and to foretell the future, we observe
      that our cooperative effort, merging surgeons and scientists, researchers and
      scholars, and authors and readers, has evolved beyond national borders. Our
      endeavor is an intercontinental, All-embracing Avant-garde of Notable Academics
      (AANA). In summary, Arthroscopy, like AANA, is global.

PMID- 29198345
TI  - Principles That Will Improve Your Physical Examination.

PMID- 29198343
TI  - Incidence of skin toxicity in squamous cell carcinoma of the head and neck
      treated with radiotherapy and cetuximab: A systematic review.
AB  - PURPOSE: Radiotherapy plus cetuximab is an effective combination therapy for
      locally advanced head and neck squamous cell carcinoma. The aim of our study was
      to determine the frequency of skin toxicity in patients receiving the combined
      treatment. RESULTS: Forty-eight studies were included in our analysis, for a
      total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and
      acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95%
      CI: 11.2-15.6), respectively. The majority of studies referred to CTCAE scales
      for reporting both side effects (85.7% and 92.1%, respectively). Data on the
      management of skin toxicity were available in only 35.4% of the reviewed
      literature. CONCLUSIONS: severe radiation dermatitis is a frequent side effect
      induced by the combination of radiotherapy and cetuximab in head and neck cancer.
      The lack of predictive biomarkers of toxicity hampers the possibilty to design
      preventive measures on a personalized basis.

PMID- 29198347
TI  - Author's Reply.

PMID- 29198346
TI  - Regarding "Hip and Anterior Cruciate Ligament Crossroads".

PMID- 29198348
TI  - Educating Surgeons-AANA's Role: Past, Present, and Future.

PMID- 29198349
TI  - Editorial Commentary: Technical Skill in Arthroscopic Simulation Training: Are
      Wearable Motion Sensors a Step Forward?
AB  - Wearable inertial sensors can be used for assessment of surgeon body motion
      during arthroscopy, with demonstrated macroergonomic differences observed between
      novices and experts during diagnostic arthroscopy of a right cadaver knee. Before
      the adoption of arthroscopy training benchmarks based on inertial sensor
      technology, validation research should cross-correlate ergonomic variables with
      surgical quality.

PMID- 29198350
TI  - Editorial Commentary: Healthy Skepticism: An Invaluable Trait.
AB  - Using a switching stick from the posterior portal is a frequently employed method
      of identifying the location for the subscapularis split for a shoulder
      arthroscopic Latarjet. However, in a recent cadaveric study, in none of the 20
      specimens studied did this technique result in the split being placed in the
      preferred position-the junction of the superior two-thirds and the inferior one
      third of the subscapularis. As a result, if the position of the coracoid graft is
      too superior, the anteroinferior extension of the glenoid arc and the vector of
      the conjoined sling may be suboptimal and fail to restrain humeral head
      translation. There is thus a need for a more reliable method for establishing the
      subscapularis split in patients with shoulder instability and significant glenoid
      bone loss. Moreover, in comparison to the open Latarjet surgical technique, an
      arthroscopic Latarjet procedure is notably more complex, technically challenging,
      and involves a demanding learning curve. For any procedure, the morbidity curve
      is inversely related to the learning curve-the lower one is on the learning
      curve, the greater the expected complications. The area beneath the morbidity
      curve is related to increased costs to manage complications and suboptimal
      outcomes. Study, practice, acquisition, and refinement of the necessary skills
      needed to perform a complex procedure should be done primarily in the cadaver
      lab. It is imperative that each of us critically evaluate our own experience and
      clinical practice to determine if we have or expect to generate the critical
      volume necessary to successfully master the arthroscopic Latarjet techniques and
      to retain the expertise needed for optimal patient outcomes.

PMID- 29198351
TI  - Editorial Commentary: Arthroscopic Latarjet Shoulder Stabilization: Where Are We?
      Where Are We Going?
AB  - Arthroscopic Latarjet procedure has shown satisfactory clinical outcomes in the
      treatment of anteroinferior shoulder instability. Although as of today there is
      no proven advantage of the arthroscopic procedure over an open one, it is too
      early to give up. At the same time, crucial to understand the causes of failure,
      to find the solutions to every single difficulty to simplify this surgery and to
      make it as accessible as possible.

PMID- 29198352
TI  - Editorial Commentary: The Wake of the Dragon: Will the Orthopaedic Community
      Adopt the Shoulder Arthroscopic Latarjet Procedure as We Adopted the Arthroscopic
      Rotator Cuff Repair?
AB  - The Latarjet procedure is a complex and difficult operation when performed both
      with an open approach and arthroscopically. The difficulties come from the fact
      that it is a combined intra- and extra-articular procedure, and that working
      close to the brachial plexus may be frightening for surgeons. Because of the high
      complication and reoperation rates reported in the literature, this procedure is,
      at the moment, rejected by a large part of the orthopaedic community,
      specifically in North America. The Chinese experience shows, after the European
      one, that arthroscopic Latarjet is an efficient and irreplaceable option for the
      treatment of recurrent anterior shoulder instability in the context of capsular
      and/or glenoid deficiency. A recent study shows that the arthroscopic procedure
      provides accurate bone block positioning and high rates of healing, excellent
      clinical results (no recurrence of instability at 2-year follow-up), and low
      rates of complications (no neurovascular injury). Although the arthroscopic
      Latarjet should be approached with caution, the learning curve should not be
      thought of as prohibitive. To learn how to perform an arthroscopic Latarjet,
      surgeons should visit an experienced surgeon and take a course to practice on
      cadavers first. Although it will take time and effort to learn and perform this
      operation correctly, we should command our Chinese colleagues to encourage us to
      follow their path. There is no reason that in the near future the orthopaedic
      community does not adopt the arthroscopic Latarjet procedure, as we adopted the
      arthroscopic rotator cuff repair and other complex surgical procedures. Among the
      strongest reasons to perform the Latarjet procedure arthroscopically are the
      accuracy of graft placement, the safety for neurovascular structures provided by
      direct visualization and magnification, and the excellent clinical results
      allowing young people to go back to sport, including high-risk (contact,
      overhead) sports.

PMID- 29198353
TI  - Editorial Commentary: When the Shoulder Joint Has Lost Stoichiometry-Does
      Arthroscopic-Assisted Latissimus Dorsi Transfer Stack Up?
AB  - Non-arthroplasty treatment options for pseudoparalysis of the shoulder are
      preferable in the younger patient population. Although there are differing
      philosophies among shoulder surgeons, many prefer to avoid reversed total
      shoulder arthroplasty for patients under age 60 years. Arthroscopically assisted
      latissimus dorsi transfer may be a good alternative for these patients, but how
      the results compare with arthroscopic superior capsular reconstruction is the
      question.

PMID- 29198354
TI  - Editorial Commentary: Pioneering the Gluteal Interval: Understanding and Treating
      Undersurface and Full-Thickness Gluteus Medius Tears of the Hip.
AB  - Lateral-based hip disease is severely impairing for many patients. Treatment
      decision making requires a thorough understanding of the biomechanical and
      clinical interpretation of the physical examination. The outcomes of these under
      recognized pathologies are explained with success. A recent study has described
      the diagnostic and surgical treatment outcomes of this impairing condition of
      partial and full-thickness gluteus medius tears.

PMID- 29198355
TI  - Editorial Commentary: Knee Lateral Collateral Ligament Injury Is More Common Than
      We Thought.
AB  - Detection of a knee lateral collateral ligament (LCL) tear, in combination with
      an anterior cruciate ligament tear, may be facilitated by the heel height test,
      which seems a modification of Hughston's external rotation recurvatum test for
      posterolateral rotatory instability. The radiographic and arthroscopic stress
      tests are also valuable. We have found that varus stress will increase varus
      opening by 1 degrees  to 4 degrees  for isolated LCL tears and 5 degrees  to 9
      degrees  for combined (LCL) popliteus injury; an arthroscopic stress evaluation
      will note a normal opening of 5 to 6 mm increasing to 9 to 10 mm in combined LCL
      popliteus injury. Generally, in our opinion and experience, partial injuries to
      the lateral side of the knee heal, and only with 9 to 10 mm of arthroscopic
      opening is posterolateral reconstruction required.

PMID- 29198356
TI  - Editorial Commentary: The Acrid Bioscrew in Anterior Cruciate Ligament
      Reconstruction of the Knee.
AB  - Bioresorbable screws have been widely adopted for graft fixation in knee anterior
      cruciate ligament (ACL) reconstruction on the promise of screw resorbtion and
      replacement by bone. When considering the value of bioresorbable screws, it is
      imperative to understand that the "A" in PGA and PLA, the base ingredient of all
      bioscrews, is for Acid. All resorb by a process of hydrolysis; the speed and
      extent of resorbtion is determined by both the acidity of the screw and the
      environment in which it is placed. Regrettably, the promise of reliable,
      predictable screw resorbtion and replacement by bone remains elusive, despite the
      addition of "osteoconductive" materials. For the most part, bioresorbables are
      associated with good clinical outcomes for ACL reconstruction; they are not
      "dangerous," just disappointing with respect to bony replacement. We propose that
      nonresorbing inert plastics such as PEEK (polyether ether ketone) may be better
      suited for the purpose of graft fixation devices for ACL reconstruction.

PMID- 29198357
TI  - Editorial Commentary: Hamstring Autograft With Preserved Insertions Versus Free
      Hamstring Autograft in Knee Anterior Cruciate Ligament Reconstruction: Clinically
      the Same but Statistically Different.
AB  - There is considerable debate over the ideal graft for anterior cruciate ligament
      (ACL) reconstruction in athletes. The use of a hamstring autograft with preserved
      insertions is an approach to ACL reconstruction that may lead to earlier healing
      and less morbidity in comparison to a free hamstring autograft. When compared in
      a randomized trial, statistically significant but clinically irrelevant
      differences in clinical outcome and instrumented laxity were observed. These
      contradictory findings highlight the importance of examining the results from
      many vantage points and further demonstrate the misleading conclusions that may
      result from reliance on P values.

PMID- 29198358
TI  - Editorial Commentary: The Acellular Osteochondral Allograft, the Emperor Has New
      Clothes.
AB  - For larger lesions (>2.5-cm2), clinical evidence and practice have shown that
      fresh osteochondral allograft have good durability, with 88% return to sport and
      greater than 75% 10-year survival rates for treatment of large femoral condyle
      lesions. That said, the use of fresh osteochondral allografts in clinical
      practice is limited by the availability of acceptable donor tissues for eligible
      patients in a timely fashion. Significant diminution of chondrocyte viability and
      density occurs during the preservation and storage period. All osteochondral
      allografts are not equal in performance and outcome. Chondrocyte density and
      viability are critical for successful transplantation and outcome in the short
      and long term. This commentary highlights the high failure rates of tissue when
      it is acellular.

PMID- 29198359
TI  - Editorial Commentary: Osteochondral Lesions of the Talus-Are We Going the Wrong
      Way?
AB  - Recalcitrant osteochondral lesions of the talus present a difficult problem to
      the treating surgeon. Anterior and posterior approaches have been studied to
      facilitate treatment access. Current research highlights the accessibility of an
      osteochondral lesion to treatment from an anterior or posterior approach and
      shows the importance of foot position and noninvasive distraction to facilitate
      treatment. Moreover, it is important to consider that using both anterior and
      posterior portals, most osteochondral lesions can be well treated with a patient
      in the supine position. Most of all, ankle arthroscopy surgeons must be sure to
      visualize the central and posterior ankle so as not to miss essential pathology.

PMID- 29198360
TI  - Editorial Commentary: Gluteal Pain Syndrome of the Hip: It's Been There All
      Along!
AB  - The diagnosis and management of deep gluteal syndrome of the hip is currently
      evolving and the lack of prospective studies makes it even more difficult to
      discern what is the appropriate treatment. The communication between physicians
      managing this problem needs to improve to coordinate care better and limit the
      amount of unnecessary studies that these patients typically undergo.

PMID- 29198361
TI  - Report of the 2017 Arthroscopy Association of North America Traveling Fellowship
      A Fellowship Odyssey.
AB  - It was an honor to be selected to participate in the 2017 Arthroscopy Association
      of North America Advanced Arthroscopy Traveling Fellowship. This year's group
      included Michael J. Alaia, M.D., Assistant Professor and Associate Sports
      Medicine Fellowship Director at NYU Hospital for Joint Diseases; Nathan K.
      Endres, M.D., Associate Professor at the University of Vermont; LCDR Patrick W.
      Joyner, M.D., Assistant Professor at Naval Medical Center Portsmouth, and Head
      Physician East Coast Navy Seals; and LTC Christopher J. Tucker, M.D., Assistant
      Professor at the Uniformed Services University and Chief of Sports Service at
      Fort Belvoir Community Hospital. This year, we were honored to have a true
      pioneer in sports medicine and arthroscopic surgery, Dr. Jack M. Bert, Past
      President of Arthroscopy Association of North America and Adjunct Clinical
      Professor at the University of Minnesota, serve as our Godfather.

PMID- 29198362
TI  - Corrigendum to "Enhancement of waste activated sludge dewaterability using
      calcium peroxide pre-oxidation and chemical re-flocculation" [(Water Res.) 103
      (2016) 170-181].

PMID- 29198363
TI  - Foreword.

PMID- 29198365
TI  - Update on current problems in colorectal liver metastasis.

PMID- 29198366
TI  - The effectiveness of self-compassion and self-esteem writing tasks in reducing
      body image concerns.
AB  - This study investigated whether single-session self-compassion and self-esteem
      writing tasks ameliorate the body image concerns evoked by a negative body image
      induction. Ninety-six female university students aged 17-25 years (Mage=19.45,
      SD=1.84) were randomly assigned to one of three writing treatment groups: self
      compassion, self-esteem, or control. After reading a negative body image
      scenario, participants completed scales measuring state body appreciation, body
      satisfaction, and appearance anxiety. They then undertook the assigned writing
      task, and completed the three measures again, both immediately post-treatment and
      at 2-week follow-up. The self-compassion writing group showed higher post
      treatment body appreciation than the self-esteem and control groups, and higher
      body appreciation than the control group at follow-up. At post-treatment and
      follow-up, self-compassion and self-esteem writing showed higher body
      satisfaction than the control. The groups did not differ on appearance anxiety.
      Writing-based interventions, especially those that enhance self-compassion, may
      help alleviate certain body image concerns.

PMID- 29198368
TI  - Trunk musculoskeletal response in maximum voluntary exertions: A combined
      measurement-modeling investigation.
AB  - Maximum voluntary exertion (MVE) tasks quantify trunk strength and maximal muscle
      electromyography (EMG) activities with both clinical and biomechanical
      implications. The aims here are to evaluate the performance of an existing trunk
      musculoskeletal model, estimate maximum muscle stresses and spinal forces, and
      explore likely differences between males and females in maximum voluntary
      exertions. We, therefore, measured trunk strength and EMG activities of 19
      healthy right-handed subjects (9 females and 10 males) in flexion, extension,
      lateral and axial directions. MVEs for all subjects were then simulated in a
      subject-specific trunk musculoskeletal model, and estimated muscle activities
      were compared with EMGs. Analysis of variance was used to compare measured
      moments and estimated spinal loads at the L5-S1 level between females and males.
      MVE moments in both sexes were greatest in extension (means of 236 Nm in males
      and 190 Nm in females) and least in left axial torque (97 Nm in males and 64 Nm
      in females). Being much greater in lateral and axial MVEs, coupled moments
      reached ~50% of primary moments in average. Females exerted less moments in all
      directions reaching significance except in flexion. Muscle activity estimations
      were strongly correlated with measurements in flexion and extension (Pearson's r
      = 0.69 and 0.76), but the correlations were very weak in lateral and axial MVEs
      (Pearson's r = 0.27 and 0.13). Maximum muscle stress was in average 0.80 +/- 0.42
      MPa but varied among muscles from 0.40 +/- 0.22  MPa in rectus abdominis to 0.99
      +/- 0.29 MPa in external oblique. To estimate maximum muscle stresses and
      evaluate validity of a musculoskeletal model, MVEs in all directions with all
      coupled moments should be considered.

PMID- 29198367
TI  - Can the introduction of a full-service supermarket in a food desert improve
      residents' economic status and health?
AB  - PURPOSE: To estimate the impacts of a new supermarket in a low-income desert, on
      residents' economic status and health. METHODS: We surveyed a randomly selected
      cohort in two low-income Pittsburgh neighborhoods before and about 1 year
      following the opening of a supermarket. We used difference-in-difference approach
      to test changes across the two neighborhoods in residents' food security, United
      States Department of Agriculture Supplemental Nutrition Assistance Program and
      Special Supplemental Nutrition Program for Women Infant and Children
      participation, employment, income, and self-reported health/chronic disease
      diagnoses. RESULTS: We observed declines in food insecurity (-11.8%, P < .01),
      Supplemental Nutrition Assistance Program participation (-12.2%, P < .01), and
      fewer new diagnoses of high cholesterol (-9.6%, P = .01) and arthritis (-7.4%, P
      = .02) in the neighborhood with the new supermarket relative to residents of the
      comparison neighborhood. We also found suggestive evidence that residents'
      incomes increased more ($1550, P = .09) and prevalence of diabetes increased less
      in the neighborhood with the supermarket than in the comparison neighborhood (
      3.6%, P = .10). CONCLUSIONS: Locating a new supermarket in a low-income
      neighborhood may improve residents' economic well-being and health. Policymakers
      should consider broad impacts of neighborhood investment that could translate
      into improved health for residents of underserved neighborhoods.

PMID- 29198369
TI  - A practical step length algorithm using lower limb angular velocities.
AB  - The use of Inertial Measurement Units (IMUs) for spatial gait analysis has opened
      the door to unconstrained measurements within the home and community. Bandwidth,
      cost limitations, and ease of use has historically restricted the number and
      location of sensors worn on the body. In this paper, we describe a four-sensor
      configuration of IMUs placed on the shanks and thighs that is sufficient to
      provide an accurate measure of temporal gait parameters, spatial gait parameters,
      and joint angle dynamics during ambulation. Estimating spatial gait parameters
      solely from gyroscope data is preferred because gyroscopes are less susceptible
      to sensor noise and a system comprised of only gyroscopes uses decreased
      bandwidth compared to a typical 9 degree-of-freedom IMU. The purpose of this
      study was to determine the validity of a novel method of step length estimation
      using gyroscopes attached to the shanks and thighs. An Inverted Pendulum Model
      algorithm (IPM) was proposed to calculate step length, stride length, and gait
      speed. The algorithm incorporates heel-strike events and average forward velocity
      per step to make these assessments. IMU algorithm accuracy was determined via
      concurrent validity with an instrumented walkway and results explained via the
      collision model of gait. The IPM produced accurate estimates of step length,
      stride length, and gait speed with a mean difference of 3 cm and an RMSE of 6.6
      cm for step length, thus establishing a new approach for spatial gait parameter
      calculation. The lack of numerical integration in IPM makes it well suited for
      use in continuous monitoring applications where sensor sampling rates are
      restricted.

PMID- 29198370
TI  - Whole genome sequencing analysis of Salmonella enterica serovar Weltevreden
      isolated from human stool and contaminated food samples collected from the
      Southern coastal area of China.
AB  - Salmonella enterica serovar Weltevreden is the most common non-typhoid Salmonella
      found in South and Southeast Asia. It causes zoonoses worldwide through the
      consumption of contaminated foods and seafood, and is considered as an important
      food-borne pathogen in China, especially in the Southern coastal area. We
      compared the whole genomes of 44 S. Weltevreden strains isolated from human stool
      and contaminated food samples from Southern Coastal China, in order to
      investigate their phylogenetic relationships and establish their genetic
      relatedness to known international strains. ResFinder analysis of the draft
      genomes of isolated strains detected antimicrobial resistance (AMR) genes in only
      eight isolates, equivalent to minimum inhibitory concentration assay, and only a
      few isolates showed resistance to tetracycline, ciprofloxacin or ampicillin. In
      silico MLST analysis revealed that 43 out of 44 S. Weltevreden strains belonged
      to sequence type 365 (CC205), the most common sequence type of the serovars.
      Phylogenetic analysis of the 44 domestic and 26 international isolates suggested
      that the population of S. Weltevreden could be segregated into six phylogenetic
      clusters. Cluster I included two strains from food and strains of the "Island
      Cluster", indicating potential inter-transmission between different countries and
      regions through foods. The predominant S. Weltevreden isolates obtained from the
      samples from Southern coastal China were found to be phylogenetically related to
      strains from Southern East Asia, and formed clusters II-VI. The study has
      demonstrated that WGS-based analysis may be used to improve our understanding of
      the epidemiology of this bacterium as part of a food-borne disease surveillance
      program. The methods used are also more widely applicable to other geographical
      regions and areas and could therefore be useful for improving our understanding
      of the international spread of S. Weltevreden on a global scale.

PMID- 29198371
TI  - Comparison of Abbott Architect(r), Siemens Immulite(r), and Diasorin Liaison(r)
      for determination of Epstein-Barr virus serological diagnosis.
AB  - This study compared the performance of 3 automated immunoassays, Architect(r)
      (Abbott), Immulite(r) (Siemens) and Liaison(r) (Diasorin), for Epstein-Barr virus
      (EBV) serology. Ninety-one serum samples collected in Amiens University Hospital
      were analyzed for the presence of Viral Capsid Antigen (VCA) IgG and IgM and
      Epstein-Barr Nuclear Antigen (EBNA) IgG. The agreement between the 3 assays was
      calculated for each marker individually and for determination of the EBV profile,
      based on interpretation of the combination of these 3 EBV markers. Although
      similar results were obtained with Architect(r) and Liaison(r), several
      discordant results were observed with Immulite(r), particularly for EBNA IgG. A
      large number of EBNA IgG-positive results were observed, which interfered with
      interpretation of the EBV profile. In contrast, Immulite(r) performed similarly
      to the 2 other assays for detection of VCA IgM.

PMID- 29198372
TI  - Klebsiella pneumoniae co-producing KPC and RmtG, finally targeting Switzerland.
AB  - A carbapenem- and pan-aminoglycoside-resistant Klebsiella pneumoniae strain was
      isolated from a Brazilian patient hospitalized in a Swiss hospital. The clinical
      isolate carried genes encoding the KPC-2 carbapenemase and the RmtG 16S rRNA
      methyltransferase. This is the first report of a carbapenem-resistant K.
      pneumoniae producing RmtG in Europe.

PMID- 29198373
TI  - The development and implementation of a layperson trauma first responder course
      in La Paz, Bolivia: A pilot study.
AB  - BACKGROUND: Ninety percent of nearly five million annual global injury deaths
      occur in low- and middle-income countries (LMICs), where prehospital care systems
      are frequently rudimentary or nonexistent. The World Health Organization
      considers layperson first-responders as essential for emergency medical services
      in low-resource settings lacking more formalized systems. This study sought to
      develop and implement a layperson trauma first responder course (TFRC) in
      Bolivia. MATERIALS AND METHODS: In March and April 2013 nine sessions of the
      eight-hour TFRC were held in La Paz, Bolivia. The course charged a nominal fee,
      and was led by an American surgeon and medical student. The TFRC built upon
      existing models with local stakeholder input, and included both didactic and
      practical components. Participants completed a baseline survey, and pre and
      posttests. The primary outcome was test performance, with secondary outcomes
      including demographic sub-group test score analyses and exam question validation.
      Data were assessed using nonparametric and psychometric methods RESULTS: One
      hundred fifty-nine individuals met study inclusion criteria. Participant median
      age was 28 (IQR 24, 36), 49.1% were male, 59.1% worked in a medical field, most
      had secondary (35.2%) or university (56.0%) level educations, and 67.3% had prior
      first aid training. Median test scores improved after course completion (48% vs.
      76%, p <0.001), along with skill confidence (4 vs. 4.5, p <0.001). Most questions
      had appropriate item difficulty indices, point bi-serial correlation
      coefficients, and positive Pretest Posttest Difference Indices. Cronbach alpha
      coefficients for pre and posttest scores were 0.72 and 0.78, respectively.
      CONCLUSIONS: This study presents data from the first offering of an original TFRC
      for laypeople in Bolivia. Increased participant knowledge and skill confidence
      after course completion, and acceptable overall psychometric test properties,
      indicate this model is valid and effective. Future aims include TFRC revision,
      and enrollment of more layperson first responders to increase population-level
      impacts.

PMID- 29198374
TI  - Surgically treated Hoffa Fractures with poor long-term functional results.
AB  - INTRODUCTION: Hoffa fractures are rare injuries and usually involve the lateral
      condyle. There are few published studies of large series of isolated coronal
      plane fractures of the femoral condyle. The aim of the study to determine the
      long-term functional outcomes and complications in surgically treated Hoffa
      fractures. PATIENTS AND METHODS: A retrospective review was made of 13
      consecutive patients who were treated surgically for an isolated coronal plane
      fracture of the distal femur posterior condyle. The patients were evaluated with
      physical examination, PA and lateral radiographs and CT at the final follow-up
      examination. Functional outcome was evaluated with the OXFORD knee scoring system
      and Knee Society Score (KSS). Pain at rest and in activity was assessed using a
      Visual Analog Scale (VAS). RESULTS: The patients comprised 11 males and 2 females
      with an average age at surgery of 27.5 years. The mean follow-up period was 93
      months (range, 62-134 months). Mean time to fracture healing was 10 weeks (range,
      8-12 weeks). The mean ROM was determined as 110 degrees , mean KSS 78,4 and mean
      Oxford knee score 38,2. The mean KSS was 66,5 for medial Hoffa fracture patients
      and it was 83,8 for lateral Hoffa fracture patients. The mean Oxford knee score
      was 33,2 for medial Hoffa fracture patients and it was 40,4 for lateral Hoffa
      fracture patients. The mean VAS at rest and in activity was 1,1 and 2,9,
      respectively. Osteoarthritis was seen in 7 (54%) patients and avascular necrosis
      in 2 (15.4%). Varus instability was determined in 1 patient and valgus
      instability in 1 patient. CONCLUSION: Hoffa fractures may easily be overlooked if
      the radiological examination is not made carefully. Screw fixation was seen to
      provide enough biomechanical stability until the fracture healed. Arthrosis is a
      frequent long-term complication which worsens the functional results. Medial
      Hoffa fractures tend to have worse functional results than lateral Hoffa
      fractures. LEVEL OF EVIDENCE: Therapeutic Level IV retrospective case series.

PMID- 29198375
TI  - The value of 'binder-off' imaging to identify occult and unexpected pelvic ring
      injuries.
AB  - AIMS: To determine the effectiveness of 'binder-off' plain pelvic radiographs in
      the assessment of pelvic ring injuries. PATIENTS AND METHODS: All patients
      requiring operative intervention at our tertiary referral pelvic unit/major
      trauma centre for high-energy pelvic injuries between April 2012 and December
      2014 were retrospectively identified. Pre-operative pelvic imaging with and
      without pelvic binder was reviewed with respect to fracture pattern and pelvic
      stability. The frequency with which the imaging without pelvic binder changed the
      opinion of the pelvic stability and need for operative intervention, when
      compared with the computed tomography (CT) scans and anteroposterior (AP)
      radiographs with the binder on, was assessed. RESULTS: Seventy-three percent (71
      of 97) of patients had initial imaging with a pelvic binder in situ. Of these,
      76% (54 of 71) went on to have 'binder-off' imaging. Seven percent (4 of 54) of
      patients had unexpected unstable pelvic ring injuries identified on 'binder-off'
      imaging that were not identified on CT imaging in binder. CONCLUSIONS: Trauma CT
      imaging of the pelvis with a pelvic binder in place is inadequate at excluding
      unstable pelvic ring injuries, and, based on the original findings in this paper,
      we recommend additional plain film 'binder-off' radiographs, when there is any
      clinical concern.

PMID- 29198376
TI  - Short- and long-term changes of the pharyngeal airway after surgical mandibular
      advancement in Class II patients-a three-dimensional retrospective study.
AB  - PURPOSE: To evaluate the short- and long-term impact of mandibular-only
      advancement on pharyngeal airway space (PAS) changes by using cone-beam computed
      tomography (CBCT) and a new segmentation software. Furthermore, to determine
      whether a correlation exists between forward movement and PAS gain. MATERIALS AND
      METHODS: A retrospective evaluation of a homogeneous cohort of Class II patients
      who had undergone mandibular-only advancement was performed. Pre- (T0), post-
      (T1), and 1-year post-operative (T2) CBCT scans were obtained in each case, and
      the changes in PAS parameters (volume and smallest cross-sectional area) were
      compared with new segmentation software. Mandibular advancement was measured and
      correlated with PAS parameters. RESULTS: A significant postoperative gain in all
      airway parameters compared with baseline was shown for T1 (p = 0.02), with an
      additional increase for T2 (p < 0.001). No significant linear association between
      the movement of the measurement points and any other PAS parameters could be
      discerned (p > 0.05). CONCLUSION: Our findings indicate that bilateral mandibular
      only advancement surgery results in a significant widening of the PAS in Class II
      patients. Long-term adaption of the PAS also occurs after surgery implying an
      additional gain of PAS over time. Sicat Air(r) software seems to be a sufficient
      and promising tool for PAS evaluation.

PMID- 29198377
TI  - Central mucoepidermoid carcinoma: An up-to-date analysis of 147 cases and review
      of prognostic factors.
AB  - OBJECTIVE: To integrate the available data published on central mucoepidermoid
      carcinoma (CMC) into a comprehensive analysis of its clinical aspects, histology,
      treatment, and prognostic factors. METHODS: An electronic search was undertaken
      in July 2017. Eligibility criteria for publications included having clinical,
      histological, treatment, and time of follow-up data to confirm the diagnosis.
      RESULTS: In addition, gender, histological grade, conservative treatment, and
      lymph node metastasis were significant independent prognostic factors.
      CONCLUSION: Male patients with histological grade III CMC of the jaw bone, who
      used conservative treatment as the main treatment, and presented with lymph node
      metastasis, were more likely to have a worse prognosis.

PMID- 29198378
TI  - Fantastic Beasts and How To Sequence Them: Ecological Genomics for Obscure Model
      Organisms.
AB  - The application of genomic approaches to 'obscure model organisms' (OMOs),
      meaning species with no prior genomic resources, enables increasingly
      sophisticated studies of the genomic basis of evolution, acclimatization, and
      adaptation in real ecological contexts. I consider here ecological questions that
      can be addressed using OMOs, and indicate optimal sequencing and data-handling
      solutions for each case. With this I hope to promote the diversity of OMO-based
      projects that would capitalize on the peculiarities of the natural history of
      OMOs and could feasibly be completed within the scope of a single PhD thesis.

PMID- 29198379
TI  - Operative shoulder instability injury management in Australian Football League
      players: A case series.
AB  - OBJECTIVES: The purpose of this study was to review the surgical management
      procedures of shoulder instability injuries in Australian Football League (AFL)
      players, and determine outcomes regarding return to sport and injury recurrence.
      DESIGN: Retrospective cohort study. METHODS: Elite AFL players with shoulder
      instability resulting in surgery were assessed in a retrospective cohort design
      (72 players/77 shoulders). Type of initial injury, surgical management, return to
      sport and injury recurrence were obtained. The mean follow-up period post-surgery
      was 2.9 years. Return to sport outcomes were compared between arthroscopic and
      open surgery using a Kaplan-Meier survival analysis. Logistic regression
      modelling was used to determine associations between injury recurrence, type of
      injury, participant age and method of surgery. RESULTS: Shoulder instability
      injuries occurred most frequently during tackling (40%). Arthroscopic surgery was
      preferred for primary shoulder instability. Nine (16%) recurrences occurred in
      those who underwent arthroscopic surgery compared to two (9%) following open
      surgery. Return to the elite level was slightly but significantly (2 weeks,
      p=0.049) longer for open compared to arthroscopic surgery. Recurrence was 5 times
      more likely if the primary injury was a dislocation and more likely in players
      who were younger at the time of surgery. CONCLUSION: Tackling was the predominant
      mechanism for shoulder instability injuries in AFL players and arthroscopic
      surgery was more commonly performed for primary injuries. Sustaining a
      dislocation as the primary injury and younger age increased the likelihood of
      recurrent instability. Careful consideration should be given to the operative
      management of these individuals.

PMID- 29198380
TI  - The Priority of Administering HIV Postexposure Prophylaxis in Cases of Sexual
      Assault in an Emergency Department.
AB  - INTRODUCTION: Contracting the human immunodeficiency virus (HIV) is a genuine
      concern for sexually assaulted patients. Emergency departments are a place where
      sexually assaulted patients seek care, including treatment to prevent HIV. Prompt
      administration of nonoccupational postexposure prophylaxis is essential because
      of the time-sensitive nature of the medications. Quality improvement measures at
      an urban hospital revealed delays in administration of postexposure prophylaxis
      to these patients. METHODS: A forensic simulation course and checklist was
      developed for emergency departments to improve care for sexually assaulted
      patients. Data used for analysis included time of administration of
      nonoccupational postexposure medication and length of stay before and after
      intervention with the simulation course and checklist. Points of measurement
      included student t-test to assess any significant differences and regression
      analysis to determine associations. RESULTS: When comparing differences between
      time of nonoccupational postexposure before and after intervention, there was a
      trend toward improving the time of administration, but it was not found to be
      significant. Before intervention, an association was found with sexually
      assaulted patients' lengths of stay and the time that nonoccupational
      postexposure medication was administered, with a regression equation of R2, 0.76.
      After intervention, this association was absent, with an R2 of 0.017. DISCUSSION:
      Implementing a simulation course and checklist for emergency nurses in caring for
      sexually assaulted patients helps to improve the timeliness of administration of
      nonoccupational postexposure medications and resolve the association between the
      length of stay and time of administration of medication.

PMID- 29198381
TI  - During the Emergency Department Evaluation of a Well-Appearing Neonate with
      Fever, Should Empiric Acyclovir Be Initiated?
AB  - BACKGROUND: Herpes simplex virus (HSV) infection represents significant morbidity
      and mortality in the neonatal period. Although clear guidelines exist on the
      evaluation and management of the otherwise well-appearing febrile neonate
      pertaining to occult serious bacterial infections, there is no standardized
      approach regarding when to initiate testing and treatment for HSV infection. It
      is vital we establish a unified guideline based on available clinical research to
      aid in our decision to evaluate and initiate therapy for this disease. METHODS: A
      PubMed search was performed using the keywords "neonate AND fever AND HSV" and
      "neonate AND fever AND acyclovir." The time period for the search was May 1982 to
      May 2016. Identified articles underwent further selection based on relevance to
      the clinical question. Selected articles then underwent detailed review and
      structured analysis. RESULTS: Our search identified 93 articles, of which 18 were
      found to be relevant to our clinical question. Recommendations were then made
      based on thorough review and analysis of the selected articles. CONCLUSIONS:
      Neonatal HSV infection carries significant morbidity and mortality if left
      untreated. High-quality clinical evidence on when to evaluate and treat for
      possible HSV infection is lacking. Based on available research, HSV infection in
      the febrile neonate should be strongly considered if age is < 21 days, or if
      presenting with concerning clinical features. If testing is performed, empiric
      treatment with high-dose acyclovir should be initiated. Additional research is
      needed to further clarify which cases mandate evaluation and treatment for HSV,
      and to better define treatment protocols.

PMID- 29198382
TI  - Periodic Bleeding Papule in the Umbilical Cicatrix.

PMID- 29198383
TI  - Comprehensively Assessing the Acute Femoral Cartilage Response and Recovery after
      Walking and Drop-Landing: An Ultrasonographic Study.
AB  - We compared the acute response and recovery of ultrasonography (US) cartilage
      outcomes (i.e., thickness, cross-sectional area, and echo intensity) between
      walking, drop-landing and control conditions in 43 young adults with no history
      of lower extremity injury. A femoral cartilage US assessment was performed before
      and after each condition to determine the acute cartilage response and recovery
      at 15, 30 and 45 min. Percentage change scores from pre- to all post-time points
      were used for analysis. Acute cartilage response and recovery were analyzed with
      a 3 * 4 (condition * time) repeated-measures analysis of variance. Greater
      deformation of the medial and lateral femoral cartilage was observed immediately
      after both the walking and drop-landing conditions compared with the control
      condition. Cartilage deformation after the drop-landing condition required longer
      time to recover compared with the walking condition. The femoral cartilage
      deformation was not accompanied by concurrent alterations in cartilage echo
      intensity.

PMID- 29198384
TI  - Corrections.

PMID- 29198385
TI  - Platelet-derived chemokines in inflammation and atherosclerosis.
AB  - Platelets are inflammatory anuclear cells with a well-established role in the
      development and manifestation of atherosclerosis. Activated platelets secrete a
      plethora of chemokines including CXCL4 or platelet factor 4 (PF4), CCL5, CXCL12
      or stromal cell derived factor-1alpha (SDF-1alpha), CXCL16 and others, which
      initiate or promote local inflammatory processes at sites of vascular injury.
      These processes are mainly mediated by the recruitment of circulating
      haematopoietic stem cells, neutrophils, monocytes or lymphocytes on vascular
      wall. Under acute ischemic conditions platelet-derived chemokines may promote the
      mobilization of bone marrow-derived progenitor cells and their homing at lesion
      sites. This review focuses on the role of platelet-derived chemokines in
      inflammation and atherosclerosis. Further, we discuss the clinical value of
      plasma levels of chemokines in the prognosis of atherosclerotic heart disease.

PMID- 29198386
TI  - X-Linked Glomerulopathy Due to COL4A5 Founder Variant.
AB  - Alport syndrome is a rare hereditary disorder caused by rare variants in 1 of 3
      genes encoding for type IV collagen. Rare variants in COL4A5 on chromosome Xq22
      cause X-linked Alport syndrome, which accounts for ~80% of the cases. Alport
      syndrome has a variable clinical presentation, including progressive kidney
      failure, hearing loss, and ocular defects. Exome sequencing performed in 2
      affected related males with an undefined X-linked glomerulopathy characterized by
      global and segmental glomerulosclerosis, mesangial hypercellularity, and vague
      basement membrane immune complex deposition revealed a COL4A5 sequence variant, a
      substitution of a thymine by a guanine at nucleotide 665 (c.T665G; rs281874761)
      of the coding DNA predicted to lead to a cysteine to phenylalanine substitution
      at amino acid 222, which was not seen in databases cataloguing natural human
      genetic variation, including dbSNP138, 1000 Genomes Project release version 01-11
      2004, Exome Sequencing Project 21-06-2014, or ExAC 01-11-2014. Review of the
      literature identified 2 additional families with the same COL4A5 variant leading
      to similar atypical histopathologic features, suggesting a unique pathologic
      mechanism initiated by this specific rare variant. Homology modeling suggests
      that the substitution alters the structural and dynamic properties of the type IV
      collagen trimer. Genetic analysis comparing members of the 3 families indicated a
      distant relationship with a shared haplotype, implying a founder effect.

PMID- 29198387
TI  - International Differences in the Location and Use of Arteriovenous Accesses
      Created for Hemodialysis: Results From the Dialysis Outcomes and Practice
      Patterns Study (DOPPS).
AB  - BACKGROUND: Vascular access practice is strongly associated with clinical
      outcomes. There is substantial international variation in the use of
      arteriovenous fistulas (AVFs) and grafts (AVGs), as well as AVF maturation time
      and location. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS:
      Hemodialysis patients participating in the prospective Dialysis Outcomes and
      Practice Patterns Study (DOPPS) from the United States, Japan, and Europe/ANZ
      (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and
      New Zealand), including 3,850 patients receiving 4,247 new AVFs and 842 patients
      receiving 1,129 new AVGs in 2009 to 2015. AVF location trends were based on
      38,868 AVFs recorded in DOPPS 1 to 5 cross-sections (1996-2015). PREDICTORS:
      Demographics, comorbid conditions, dialysis vintage, body mass index, facility
      percentage AVF use, median blood flow rate, and AVF location. OUTCOMES: AVF
      location; successful AVF/AVG use (>=30 days of continuous use); time-to-first
      successful AVF/AVG use (maturation). RESULTS: During DOPPS 1 to 5, the percentage
      of AVFs created in the lower arm was consistently >=93% in Japan and 65% to 77%
      in Europe/ANZ, but in the United States, this value declined from 70% (DOPPS 1)
      to 32% (DOPPS 5). Patient characteristics associated with AVF location differed
      by region. Successful AVF use was 87% in Japan, 67% in Europe/ANZ, and 64% in the
      United States, whereas successful AVG use was 86%, 75%, and 78%, respectively.
      Successful AVF use was greater for upper- versus lower-arm AVFs in the United
      States, with little difference in Europe/ANZ and the opposite pattern in Japan.
      Median time until first successful AVF use was 10 days in Japan, 46 days in
      Europe/ANZ, and 82 days in United States; until first successful AVG use: 6, 24,
      and 29 days, respectively. LIMITATIONS: Potential measurement error related to
      chart data abstraction in multiple hemodialysis facilities. CONCLUSIONS: Large
      international differences exist in AVF location, predictors of AVF location,
      successful use of AVFs, and time to first AVF/AVG use, challenging what
      constitutes best practice. The large US shift from lower- to upper-arm AVFs
      raises serious concerns about long-term health implications for some patients and
      how policies and practices aimed at increasing AVF use have affected AVF
      placement location.

PMID- 29198388
TI  - Patient-Reported Outcome Measures for Fatigue in Patients on Hemodialysis: A
      Systematic Review.
AB  - BACKGROUND: Fatigue is a prevalent and debilitating symptom in patients receiving
      hemodialysis. We aimed to identify and evaluate the characteristics and
      psychometric properties of patient-reported outcome measures for fatigue in
      patients receiving hemodialysis, to inform the selection of a robust and feasible
      measure for use in randomized trials in hemodialysis. STUDY DESIGN: Systematic
      review of outcome measures for fatigue. SETTING & POPULATION: Patients receiving
      hemodialysis. SEARCH STRATEGY & SOURCES: MEDLINE, Embase, PsycINFO, and CINAHL
      from inception to April 2017 were searched for all studies that reported fatigue
      in patients receiving hemodialysis. ANALYTICAL APPROACH: With a focus on
      addressing methods, items (individual questions) from all measures were
      categorized into content and measurement dimensions of fatigue. We assessed the
      general characteristics (eg, number of items and cost) and psychometric
      properties of all measures. RESULTS: From 123 studies, we identified 43 different
      measures: 24 (55%) were developed specifically for the hemodialysis population
      (of which 18 were nonvalidated author-developed measures for use in their study
      only), 17 (40%) for other populations, and 2 (5%) for chronic kidney disease (all
      stages). The measures assessed 11 content dimensions of fatigue, the 3 most
      frequent being level of energy (19 [44%]), tiredness (15 [35%]), and life
      participation (14 [33%]); and 4 measurement dimensions: severity (34 [79%]),
      frequency (10 [23%]), duration (4 [9%]), and change (1 [2%]). The vitality
      subscale of the 36-Item Short Form Health Survey (SF-36) was the most frequently
      used (19 [15%] studies), but has only been tested for reliability in
      hemodialysis. Of the fatigue-specific measures, the Chalder Fatigue Scale was the
      only one evaluated in hemodialysis, but the full psychometric robustness remains
      uncertain. LIMITATIONS: For feasibility, we searched for validation studies in
      the hemodialysis population using the names of measures identified in the primary
      search strategy. CONCLUSIONS: A very wide range of measures have been used to
      assess fatigue in patients receiving hemodialysis, each varying in content and
      length. Many have limited validation data available in this population. A
      standardized and psychometrically robust measure that captures dimensions of
      fatigue that are important to patients is needed to estimate and improve this
      disabling complication of hemodialysis.

PMID- 29198389
TI  - Cumulative dose of radiation therapy of hepatocellular carcinoma patients and its
      deterministic relation to radiation-induced liver disease.
AB  - This study aimed to investigate the relationship between dose and radiation
      induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC)
      receiving 3-dimensional conformal radiotherapy (3DCRT). Twenty-three patients
      with HCC who received conventional fractionated 3DCRT, including 7 who were
      diagnosed with classic RILD, were enrolled in this retrospective investigation.
      Cone-beam computed tomography (CBCT) scans were acquired at the time of treatment
      for each patient. The beams from each patient's treatment plan were applied to
      each pretreatment CBCT (the modified CBCT or mCBCT) to construct the delivered
      dose distribution of the day considering inter-treatment anatomy changes. The
      daily doses were summed together with the help of deformable image registration
      (DIR) to obtain the adjusted cumulative dose (Dadjusted). The dose changes to the
      normal liver between the original planned dose (Dplan) and Dadjusted were
      evaluated by V20, V30, V40, and the mean dose to normal liver (MDTNL). Univariate
      analysis was performed to identify the significant dose changes. Among the 23
      patients, the liver V20, V30, V40, and MDTNL showed significant differences
      between Dplan and Dadjusted, with average values of these parameters increased by
      4.1%, 4.7%, 4.5%, and 3.9 Gy, respectively (p < 0.05). The adjusted liver dose in
      21 patients (91%) was higher than the planned value. For patients without and
      with RILD,the MDTNL was increased on average by 3.5 Gy and 4.7 Gy, and normal
      tissue complication probability (NTCP) increased on average by 2.8% and 7.5%,
      respectively. Our study found that the adjusted cumulative dose based on
      calculations using pretreatment mCBCT differs significantly from planned dose;
      the use of the dosimetric results of the initial plan was found to be less
      predictive of RILD as compared with Dadjusted. Determination of a reconstructed
      Dadjusted using the mCBCT scans are more accurate in predicting RILD and has the
      potential to reduce the risk of RILD.

PMID- 29198390
TI  - Comparison between DVH-based doses and ICRU point-based doses to the rectum and
      the bladder using CT-based high-dose rate brachytherapy to the cervix.
AB  - Traditionally, doses to the bladder and the rectum were quantified using the
      bladder and rectal reference points defined by the International Commission on
      Radiation Units and Measurements (ICRU) in Report No. 38. In this study, we
      compared the 0.1-, 1.0-, 2.0-cc doses to the bladder and the rectum with the
      corresponding ICRU point doses using computed tomography (CT)-based planning in
      the intracavitary brachytherapy of carcinoma of the cervix. CT datasets of 136
      consecutive intracavitary brachytherapy insertions between January and May 2015
      were analyzed. The bladder and the rectum were contoured on consecutive CT slices
      as per Groupe Europeen de Curietherapie and the European Socie Ty for
      Radiotherapy and Oncology recommendations. Dose volume histograms were generated
      and doses of 0.1, 1.0, and 2.0 cc to the bladder and the rectum were recorded.
      ICRU bladder and rectal points were identified in the treatment plan. Mean doses
      of 0.1, 1.0, and 2.0 cc to the bladder was found to be 2.02, 1.57, and 1.35 times
      the ICRU point dose, respectively. The maximum dose received by the bladder was
      found to be 5.83 times the average ICRU point dose. Mean doses of 0.1, 1.0, and
      2.0 cc to the rectum were found to be 1.12, 0.90, and 0.78 times the ICRU rectal
      point dose, respectively. The maximum dose received by the rectum was 4.79 times
      the average ICRU point dose. The Pearson correlation coefficient value (r) was
      found to be 0.639 for D2cc and ICRU bladder point values. The Pearson correlation
      coefficient value was found to be 0.752 for D2cc and ICRU rectal point values.
      Our results show that the ICRU bladder points underestimated the dose to the
      bladder, which is in agreement with other studies. ICRU rectal point doses were
      higher than the corresponding D2cc doses. However, there was a good correlation
      between D2cc and ICRU point doses for both the bladder and the rectum.

PMID- 29198391
TI  - Spondylolysis in the past: A case study of hunter-gatherers from Southern
      Patagonia.
AB  - Spondylolysis is a fracture of the pars interarticularis, the portion of the
      neural arch that lies between the superior articular facets and the inferior
      articular facets. Clinical evidence has suggested repetitive trauma to be the
      most probable cause, even though morphological weakness of the vertebra is
      probably also involved. Prevalence is between 3% and 8% in modern populations,
      while in archaeological samples it varies from 0% to 71.4%. Considering that very
      little data about this condition is available in past populations from the
      southern extreme of South America, the aim of this paper is to analyze the
      spondylolysis in a human skeletal sample from Southern Patagonia and, at the same
      time, to explore the prevalence of spondylolysis in archaeological contexts
      around the world to gain a better understanding of the results presented here.
      The Southern Patagonian skeletal series analyzed here showed a prevalence of 20%,
      with lower prevalence in the pre contact sample (11.1%) than in the contact
      period (23.1%). Skeletons from the Salesian Mission "Nuestra Senora de La
      Candelaria" showed a higher prevalence (25%) than the sample of skeletal remains
      recovered from outside the mission (20%), suggesting that changes in lifestyle of
      hunter-gatherers during contact could be implicated in the development of
      spondylolysis in this sample. A worldwide survey displays a wide range of
      prevalence figures in American and Asian samples and low diversity between
      African and European populations. Hunter-gatherers from Southern Patagonia showed
      similar values to those observed in other American samples.

PMID- 29198392
TI  - Reprint of-Differential diagnosis: Trepanation.
AB  - Trepanation is the scraping, cutting, or drilling of an opening (or openings)
      into the neurocranium. World surveys reveal that a number of ancient cultures
      experimented with cranial surgery, and that in some areas these practices
      continued into modern times. Archaeological discoveries of possible trepanations
      continue to be made, often from geographic areas or time periods from which the
      practice was not previously known. Unfortunately, most of these reports describe
      single crania with healed defects interpreted as trepanations. When evaluating a
      possible trepanation in a skull that lacks medical history or comes from an
      archaeological context where there is no other evidence that such operations were
      performed, a thorough differential diagnosis is essential. Identification of
      unhealed trepanations is a relatively straightforward exercise, since tool marks
      provide direct evidence of surgical intervention. A confident diagnosis is more
      difficult in healed defects of the skull, where the mechanism that produced an
      opening may be obscured by bone remodeling. There are many possible causes of
      defects of the skull vault, including congenital and developmental anomalies,
      trauma, infection, neoplasm, and taphonomic damage. For this reason, a careful
      differential diagnosis is essential for identifying surgical intervention and
      distinguishing it from cranial defects caused by other mechanisms.

PMID- 29198393
TI  - Differential diagnosis in archaeology.
AB  - Diagnosing archaeological bone specimens can be likened to practices used in
      medical and veterinary medical health care. Increasing the rigor of
      archaeological diagnosis can be supported by a systematic approach derived from
      health care settings. The process of information synthesis and diagnosis can be
      viewed as being very similar among these disciplines. A first diagnostic step is
      developing an Initial Information Set (sometimes called an Initial Database in
      health care environments) from descriptive data about the archaeological specimen
      or the patient, accompanied by recording environmental and ecological
      observations. The second diagnostic step is to develop an Expanded Information
      Set that includes structured physical examination, constructing a problem list,
      and considering potential differential diagnoses for each recorded problem.
      Subsequently, a Diagnostics Information Set consists of outcomes of carefully
      selected diagnostic testing, and a Diagnostic Assessment is developed from an
      orderly mental synthesis of information across Information Sets. Critical aspects
      of a structured and orderly process are preparing inclusive differential
      diagnoses, thorough mental synthesis across Information Sets, and recognizing
      that a short list of the most plausible diagnostic alternatives may represent the
      furthest possible extent of the evaluation for many archaeological bone
      specimens.

PMID- 29198394
TI  - Reestablishing rigor in archaeological parasitology.
AB  - Archaeological parasitology originated in the mid-twentieth century with
      interdisciplinary teams of specialists directed by archaeologists. The goals of
      such studies were detailed analyses of dietary, medicinal, and environmental
      factors that shaped the patterns of infection. By the 1970s, a cadre of unique
      coprolite analysts was trained to analyze macroscopic and microscopic remains for
      integrated reconstructions of the cultural determinants of parasitism. During
      these first phases of research, diagnostic rigor was maintained by direct
      training of specialists in parasitology and archaeology sub-disciplines including
      archaeobotany and archaeopalynology. Near the end of the twentieth century,
      however, "paleoparasitology" was defined as a separate field focusing on defining
      parasite distribution through time and space. Ironically, this focus resulted in
      an increase in misdiagnosis, especially prominent after 2000. Paleoparasitology
      does not explicitly include other specialized studies in it research design.
      Thus, dietary, environmental and medicinal inferences have been neglected or lost
      as samples were destroyed solely for the purpose of parasitological analysis.
      Without ancillary archaeological studies, paleoparasitology runs the risk of
      separation from archaeological context, thereby reducing its value to the
      archaeologists who recover samples for analysis.

PMID- 29198395
TI  - Digital data recording and interpretational standards in mummy science.
AB  - Beginning during the late19th century, paleoimaging has played an ever-expanding
      role in mummy science. Increasingly during the 21st century, digital radiographic
      data collected through imaging efforts have become significant. The rapid influx
      of imaging data raises questions regarding standardized approaches to both
      acquisition and interpretation. Reports using digital data presented without
      contextual considerations commonly lead to interpretational errors. Digital data
      recording and interpretation require rigorous methodology and standards in order
      to achieve reproducibility, accuracy and minimization of inter- and intra
      observer error. Researchers applying paleoimaging methods in bioarchaeological
      research must understand the significant limitations inherent in data collection
      and interpretation from various digital data recording methods. Currently, vast
      amounts of digital data are being archived, allowing greater potential for
      hypothesis-based research and informed diagnosis by consensus. Digital databases
      hold great potential in preparing both radiologists and bioarchaeologists in the
      appropriate application and interpretation of digital data.

PMID- 29198396
TI  - No stone unturned: The presence of kidney stones in a skeleton from 19th century
      Peoria, Illinois.
AB  - During the excavation of the 19th century Peoria City Cemetery (Peoria,
      Illinois), a skeleton of a female, aged 20-30 years old, was found with large,
      bilateral calcified masses in the abdominal region. The masses were analyzed by
      Fourier transform infrared (FTIR) spectroscopy, and the results compared to
      published clinical data in an effort to determine the etiology of the stones. The
      calcified masses were determined to be staghorn struvite uroliths, which commonly
      result from chronic urinary tract infection and likely impacted the overall
      health of this individual.

PMID- 29198397
TI  - Trends in mortality and biological stress in a medieval polish urban population.
AB  - Urbanization in pre-modern populations may have had a variety of consequences
      related to population crowding. However, research on the effects of urbanization
      have provided inconsistent results regarding the biological impact of this
      transition on human populations. The purpose of this study is to test the
      hypothesis that urbanization caused an increase in overall biological stress in a
      medieval (10th-13th centuries AD) Polish population. A human skeletal sample
      (n=164) was examined for the presence of porotic hyperostosis, cribra orbitalia,
      linear enamel hypoplasia, periosteal reaction, and specific infectious diseases.
      Prevalence rates were compared among three temporal samples: initial
      urbanization, early urbanization, and later urbanization. Results indicate no
      significant trends for any of the pathological conditions. Cox proportional
      hazards analyses, however, revealed a significant increase in the risk of death
      over time, which supports the hypothesis. These results reflect the necessity of
      using multiple analyses to address bioarchaeological questions. The lack of
      significant results from skeletal indicators may be due to an earlier
      urbanization trend in the population. This study illustrates that the association
      of urbanization with elevated biological stress is complicated and dependent on
      various factors, including culture and time period.

PMID- 29198398
TI  - Intestinal parasites from the 2nd-5th century AD latrine in the Roman Baths at
      Sagalassos (Turkey).
AB  - The aim of this research was to determine the species of intestinal parasite
      present in a Roman Imperial period population in Asia Minor, and to use this
      information to improve our understanding of health in the eastern Mediterranean
      region in Roman times. We analyzed five samples from the latrines of the Roman
      bath complex at Sagalassos, Turkey. Fecal biomarker analysis using 5beta-stanols
      has indicated the feces were of human origin. The eggs of roundworm (Ascaris)
      were identified in all five samples using microscopy, and the cysts of the
      protozoan Giardia duodenalis (which causes dysentery) were identified multiple
      times in one sample using ELISA. The positive G. duodenalis result at Sagalassos
      is particularly important as it represents the earliest reliable evidence for
      this parasite in the Old World (i.e. outside the Americas). As both these species
      of parasite are spread through the contamination of food and water by fecal
      material, their presence implies that Roman sanitation technologies such as
      latrines and public baths did not break the cycle of reinfection in this
      population. We then discuss the evidence for roundworm in the writings of the
      Roman physician Galen, who came from Pergamon, another town in western Asia
      Minor.

PMID- 29198399
TI  - Influence of physiological stress on the presence of hypoplasia and fluctuating
      asymmetry in a medieval population from the village of Sypniewo.
AB  - This study aims to estimate the levels of physiological stress in the medieval
      rural population of Sypniewo by evaluating patterns of fluctuating asymmetry (FA)
      and enamel hypoplasia (EH), and provide information on the influence of
      physiological stress during the prenatal and perinatal period on early childhood
      development. Stress is defined as any external or internal condition that
      challenges homeostasis of an organism. FA is associated with physiological stress
      occurring mainly during prenatal development and early childhood. The level of FA
      is thought to reflect the intensity of the stressor(s). EH is caused by
      physiological stress such as nutritional instability during the first years of
      life. The studied material consisted of 126 skulls from the village of Sypniewo
      (Poland). Cranial radiographs were taken in postero-anterior (P-A) and basal
      views. The images were scanned and calibrated. Measurements of the cranium were
      used to estimate FA. The presence of EH was assessed using standard
      anthropological methods The highest levels of FA were observed in the region of
      the cranial base. EH was observed in 29% of individuals from the rural skeletal
      series. There was no statistically significant correlation between FA and EH
      occurrence or between sex and the studied stress indicators.

PMID- 29198400
TI  - Osteochondritis Dissecans of skeletal elements of the foot in a 19th century
      rural farming community from The Netherlands.
AB  - Osteochondritis Dissecans (OD) is a pathological condition of the subchondral
      bone and surrounding cartilage of synovial joints, associated with strenuous
      activity and/or trauma. Reports of OD in archaeological skeletal remains are few
      and the majority demonstrate low OD prevalence (<1%). A predominantly 19th
      century skeletal sample from Middenbeemster, the Netherlands, was assessed for
      OD. The sample included adult individuals of both sexes. There were no definitive
      OD lesions in non-pedal elements, yet 12.9% of individuals suffered from pedal
      OD. Few archaeological and clinical reports specify the prevalence of pedal OD.
      According to the few that do, the Middenbeemster pedal OD prevalence is
      distinctly high. Several factors could have contributed to this. First, the rural
      Beemster community was centered around cattle farming, requiring extensive
      outside work and animal maintenance; thus, increasing the chances of
      acute/repetitive trauma in the foot. Second, the footwear worn during that period
      in the Netherlands was the wooden clog. It is suggested that the hard and
      inflexible clog, which is poor at absorbing shock and limits the movement of the
      foot, could have resulted in repetitive microtrauma. These two factors combined
      may have caused a high frequency of OD.

PMID- 29198401
TI  - Wounded to the bone: Digital microscopic analysis of traumas in a medieval mass
      grave assemblage (Sandbjerget, Denmark, AD 1300-1350).
AB  - Battle-related mass burials are considered the most unequivocal evidence of past
      violence. However, most published studies involve only macroscopic analysis of
      skeletal remains, commonly arriving only at broad conclusions regarding trauma
      interpretation. The current study considers a possible avenue for achieving both
      greater detail and accuracy through digital microscopy. Patterns of injury were
      investigated among 45 individuals from a Medieval Danish mass grave (Sandbjerget,
      AD 1300-1350). Injuries were recorded on every anatomical element, except hand
      and foot bones. Each was photographed and cast, facilitating remote evaluations.
      Macroscopic analysis was compared with digital microscopy in order to test the
      relative utility of the latter in characterizing skeletal injuries (mechanism,
      weapon class, direction, timing of injury). The location of 201 observed
      injuries, mainly sharp force defects, suggested that many lesions were probably
      not inflicted by face-to-face opponents. Some microscopic features were
      indicative of a specific lesion type and weapon class. Digital microscopy was
      therefore demonstrated to be a complementary tool to macroscopic assessment,
      enhancing feature observation and quantification and serving to compensate for
      many of the limitations of macroscopic assessment.

PMID- 29198402
TI  - Introduction: Scientific rigor in paleopathology.
AB  - This introductory chapter to the Special Issue on "Scientific Rigor in
      Paleopathology" serves to orient and introduce the chapters that follow through a
      detailed consideration of paleopathology as a 21st century intellectual field. In
      this vein, we first make the significant point that paleopathology is a
      profoundly interdisciplinary endeavor, encompassing aspects of the biomedical
      science, the humanities, and the social sciences. Thus, we suggest that no one
      practitioner can personally command the range of skills necessary for a 21st
      century paleopathologist. To maintain rigor in differential diagnosis, we
      emphasize collaborations and consider key concepts that illustrate the basic
      knowledge from each of these fields that any paleopathologist should command. We
      then address the manner in which disease diagnosis should proceed as a scientific
      endeavor. To illustrate scientific rigor in differential diagnosis, we present
      two case studies drawn from 1970s contributions by Cook and by Buikstra. Finally,
      we introduce Chapters 2-6, which address differential diagnosis in contexts
      ranging from specific conditions (scurvy, trepanation) to broader field-wide
      considerations (paleoparasitology, historical paleopathology, imaging, animal
      paleopathology).

PMID- 29198403
TI  - Improving the use of historical written sources in paleopathology.
AB  - The texts written by the people of past societies can provide key information
      that enhances our understanding of disease in the past. Written sources and art
      can describe cultural contexts that not only help us interpret lesions in
      excavated human remains, but also provide evidence for past disease events
      themselves. However, in recent decades many biohistorical articles have been
      published that claim to diagnose diseases present in past celebrities or well
      known individuals, often using less than scholarly methodology. This article aims
      to help researchers use historical written sources and artwork responsibly, thus
      improving our understanding of health and disease in the past. It explores a
      broad range of historical sources, from medical texts and histories to legal
      documents and tax records, and it highlights how the key to interpreting any past
      text is to understand who wrote it, when it was written, and why it was written.
      Case studies of plague epidemics, crucifixion, and the spinal deformity of King
      Richard III are then used to highlight how we might better integrate
      archaeological and historical evidence. When done well, integrating evidence from
      both archaeological and historical sources increases the probability of a
      complete and well-balanced understanding of disease in past societies.

PMID- 29198404
TI  - Paleopathological rigor and differential diagnosis: Case studies involving
      terminology, description, and diagnostic frameworks for scurvy in skeletal
      remains.
AB  - Diverse pathological processes can produce overlapping or even indistinguishable
      patterns of abnormal bone formation or destruction, representing a fundamental
      challenge in the understanding of ancient diseases. This paper discusses
      increasing rigor in differential diagnosis through the paleopathological study of
      scurvy. First, paleopathology's use of descriptive terminology can strive to more
      thoroughly incorporate international standards of anatomical terminology. Second,
      improved observation and description of abnormal skeletal features can help
      distinguish between anemia or vitamin C deficiency. Third, use of a structured
      rubric can assist in establishing a more systematic, replicable, and precise
      decision-making process in differential diagnosis. These issues are illustrated
      in the study of two new cases of suspected scurvy from northern Peru. From this,
      it appears possible that ectocranial vascular impressions may further examined as
      a morphological marker of scurvy in the skeleton. Also, increased
      paleopathological attention to pellagra is long overdue, especially as it may
      produce generally comparable lesions to scurvy. This paper reflexively speaks to
      the process of paleopathological problem solving and the epistemology of our
      discipline-particularly regarding the ways in which we can continuously improve
      description and the construction of diagnostic arguments.

PMID- 29198405
TI  - Intraoperative New-onset Left Ventricle Outflow Tract Obstruction.

PMID- 29198406
TI  - Comparison of the Effect of Aliskiren Versus Negative Controls on Aortic
      Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the effect of
      aliskiren on aortic stiffness in patients with Marfan syndrome (MS). METHODS:
      Twenty-eight MS patients (mean age +/- standard deviation: 32.6 +/- 10.6 years)
      were recruited from November 2009 to October 2014. All patients were receiving
      atenolol as standard beta-blocker therapy. A prospective randomization process
      was performed to assign participants to either aliskiren treatment (150-300mg
      orally per day) or no aliskiren treatment (negative control) in an open-label
      design. Central aortic distensibility and central pulsed wave velocity (PWV) by
      magnetic resonance imaging (MRI), peripheral PWV, central aortic blood pressure
      and augmentation index by peripheral tonometry, and aortic dilatation by
      echocardiography were examined initially and after 24 weeks. The primary endpoint
      was central aortic distensibility by MRI. RESULTS: In analyses of differences
      between baseline and 24 weeks for the aliskiren treatment group vs the negative
      control group, central distensibility (overall; P = .26) and central PWV (0.2 +/-
      0.9 vs 0.03 +/- 0.7 [m/s]; P = .79) by MRI were not significantly different.
      Central systolic aortic blood pressure tended to be lower by 14mmHg in patients
      in the aliskiren treatment group than in the control group (P = .09). A
      significant decrease in peripheral PWV (brachial-ankle PWV) in the aliskiren
      treatment group (-1.6 m/s) compared with the control group (+0.28 m/s) was noted
      (P = .005). CONCLUSIONS: Among patients with MS, the addition of aliskiren to
      beta-blocker treatment did not significantly improve central aortic stiffness
      during a 24-week period.

PMID- 29198407
TI  - Needle use and dosimetric evaluation in cervical cancer brachytherapy using the
      Utrecht applicator.
AB  - BACKGROUND AND PURPOSE: To analyse the clinical use of needles and examine the
      feasibility to meet the planning criteria in three fractions of cervical cancer
      brachytherapy. Furthermore, to investigate whether the needles with the largest
      discrepancy between application and loading are essential to treatment planning.
      MATERIALS AND METHODS: For 22 patients we analysed the applied and loaded needle
      patterns, and examined the dosimetric results for small (<30 cm3) and large (>=30
      cm3) CTVHR. We removed from the clinical plans (CP) the needles applied most, but
      with the lowest loading frequency and intensity and re-optimized these plans
      (RP). RESULTS: On average 5.8 needles were applied and 4.8 loaded per fraction,
      with average intensity 22% (17% for small, 29% for large CTVHR). Mid-lateral
      needles were applied and loaded most frequently and intensely. The average CTVHR
      D90% prescribed dose was 88.8 Gy (SD 4.2) EQD210, the average OAR [Formula: see
      text] limit was respected. Omitting the mid-ventral needles, minimal
      statistically significant differences were found in dose distributions between RP
      and CP. CONCLUSIONS: Applying on average 5.8 needles per fraction it was possible
      to meet the planning criteria for targets and OARs in three BT fractions for both
      small and large CTVHR. The mid-ventral needles were not essential in treatment
      planning, unless situated in the vicinity of the GTVres.

PMID- 29198408
TI  - Estimating the number of fractions by tumour site for European countries in 2012
      and 2025: An ESTRO-HERO analysis.
AB  - BACKGROUND AND PURPOSE: The optimal number of radiotherapy fractions is a
      relevant input for planning resource needs. An estimation of the total number of
      fractions by country and tumour site is assessed for 2012 and 2025. METHODS:
      European cancer incidence data by tumour site and country for 2012 and 2025 were
      extracted from the GLOBOCAN database. Incidence and stage data were introduced in
      the Australian Collaboration for Cancer Outcomes Research and Evaluation (CCORE)
      model, producing an evidence-based proportion of incident cases with an
      indication for radiotherapy and fractions by indication. An indication was
      defined as a clinical situation in which radiotherapy was the treatment of
      choice. RESULTS: The total number of fractions if radiotherapy was given
      according to guidelines to all patients with an indication in Europe was
      estimated to be 30 million for 2012; with a forecasted increase of 16.1% by 2025,
      yet with differences by country and tumour. The average number of fractions per
      course was 17.6 with a small range of differences following stage at diagnosis.
      Among the treatments with radical intent the average was 24 fractions, while it
      decreased to 2.5 among palliative treatments. DISCUSSION: An increase in the
      total number of fractions is expected in many European countries in the coming
      years following the trends in cancer incidence. In planning radiotherapy
      resources, these increases should be balanced to the evolution towards
      hypofractionation, along with increased complexity and quality assurance.

PMID- 29198409
TI  - Ischemic complications in Takayasu's arteritis: A meta-analysis.
AB  - OBJECTIVES: Takayasu's arteritis (TAK) is a rare vasculitis affecting the large
      blood vessels with significant morbidity and mortality from ischemic
      complications. The objective of this meta-analysis is to determine the proportion
      of TAK patients with severe ischemic complications. METHODS: We performed a
      literature search using MEDLINE, EMBASE, and the Cochrane library from database
      inception to March 2016. We included articles that reported at least one severe
      ischemic complication. A random effects model with inverse-variance weighting was
      performed to estimate the pooled proportion of TAK subjects with ischemic
      complications. RESULTS: In all, 35 studies met inclusion criteria, representing
      3262 TAK patients. All studies were observational and of low to moderate quality.
      Mean age at symptom onset or at diagnosis ranged from 10 to 49 years and mean
      delay from symptom onset to diagnosis ranged from 2 months to 7.6 years. Study
      follow-up times were from 22 months to 17 years. The majority of studies had >70%
      female subjects. The pooled prevalence of stroke in TAK was 8.9% (95% CI: 7.0
      10.9%) and of MI was 3.4% (95% CI: 2.1-4.8%) at any time during the disease
      course. There was moderate-to-severe heterogeneity across the studies (stroke: I2
      = 64.9%; MI: I2 = 74.0%). Other ischemic complications were inconsistently
      reported. CONCLUSION: Stroke and MI are common in TAK patients. Further studies
      are needed to identify predictors and preventative measures for severe ischemic
      events in TAK patients.

PMID- 29198410
TI  - Combined, short-term exposure to reduced seawater pH and elevated temperature
      induces community shifts in an intertidal meiobenthic assemblage.
AB  - In future global change scenarios the surface ocean will experience continuous
      acidification and rising temperatures. While effects of both stressors on marine,
      benthic communities are fairly well studied, consequences of the interaction of
      both factors remain largely unknown. We performed a short-term microcosm
      experiment exposing a soft-bottom community from an intertidal flat in the
      Westerscheldt estuary to two levels of seawater pH (ambient pHT = 7.9, reduced
      pHT = 7.5) and temperature (10  degrees C ambient and 13  degrees C elevated
      temperature) in a crossed design. After 8 weeks, meiobenthic community structure
      and nematode staining ratios, as a proxy for mortality, were compared between
      treatments and structural changes were related to the prevailing abiotic
      conditions in the respective treatments (pore water pHT, sediment grain size,
      total organic matter content, total organic carbon and nitrogen content,
      phytopigment concentrations and carbonate concentration). Pore water pHT profiles
      were significantly altered by pH and temperature manipulations and the
      combination of elevated temperature and reduced pH intensified the already more
      acidic porewater below the oxic zone. Meiofauna community composition was
      significantly affected by the combination of reduced pH and elevated temperature
      resulting in increased densities of predatory Platyhelminthes, reduced densities
      of Copepoda and Nauplii and complete absence of Gastrotricha compared to the
      experimental control. Furthermore, nematode staining ratio was elevated when
      seawater pH was reduced pointing towards reduced degradation rates of dead
      nematode bodies. The observed synergistic interactions of pH and temperature on
      meiobenthic communities and abiotic sediment characteristics underline the
      importance of multistressor experiments when addressing impacts of global change
      on the marine environment.

PMID- 29198411
TI  - Epileptic spasms secondary to acute cerebral and cerebellar encephalitis.
AB  - BACKGROUND: Patients with infection-related acute encephalitis sometimes develop
      epilepsy in the chronic phase of the disease. Patients with postencephalitic
      epilepsy usually develop partial seizures due to the lesions generated by the
      encephalitis. We report a case who developed late-onset epileptic spasms after
      acute cerebral and cerebellar encephalitis. CASE REPORT: A 5-year-old girl showed
      severe tremor, gait ataxia, partial or generalized tonic-clonic seizures,
      hyperactivity, and panic attacks after a mild enterocolitis. Her cerebellar
      symptoms disappeared until 3 months after onset, and her seizures were controlled
      with carbamazepine. However, the seizures reappeared as epileptic spasms 5 months
      after onset. The anti-NMDA-type glutamate receptor antibody concentration was
      significantly elevated in her cerebrospinal fluid at 8 days, 10 months, and 15
      months after onset. The spasms were resistant to multiple antiepileptic drugs.
      High-dose methylprednisolone and high-dose immunoglobulin therapies did not show
      any benefits. Oral pranlukast hydrate was started 17 months after onset. After 3
      weeks of the medication, her seizures disappeared, and her behavior also
      dramatically improved. CONCLUSION: We presented a rare case of post-encephalitic
      epilepsy that manifested as epileptic spasms. Pranlukast significantly improved
      her seizures.

PMID- 29198412
TI  - Intimate partner violence during pregnancy and perinatal mental disorders in low
      and lower middle income countries: A systematic review of literature, 1990-2017.
AB  - Mental health consequences of intimate partner violence (IPV) against pregnant
      and postpartum women are poorly understood in low and lower-middle-income
      countries (LLMIC). We systematically reviewed the evidence from 24 studies (1990
      2017) selected via a comprehensive search strategy with 14 inclusion, exclusion,
      and quality-control criteria to assess the extent to which intimate partner
      violence during pregnancy adversely affects perinatal mental disorders among
      participants in 10 LLMIC across 4 economic regions. Mostly cross-sectional,
      studies included 61-1369 participants selected randomly (88%) or non-randomly
      (12%) from purposively selected 1-6 clinics or 1-50 communities. Multivariate
      logistic regression was most frequently used (68%) for association estimates,
      adjusting for 3-16 socio-demographic variables pertinent to: women; husbands;
      and/or households. The prevalence of physical IPV ranged 2-35% among
      participants; sexual IPV ranged 9-40%; and psychological IPV ranged 22-65%. The
      prevalence of antenatal and postnatal depression ranged 15-65% and 5-35% among
      participants, respectively. Suicidal ideation ranged 5-11% during pregnancy and 2
      22% during the postpartum period. Study participants who had experienced IPV had
      1.69-3.76 and 1.46-7.04 higher odds of antenatal and postnatal depression
      compared to those who had not, depending on country, and IPV type and severity.
      Considering the strong association between IPV and mental disorders, efforts
      should focus on developing IPV interventions aimed at preventing pregnancy during
      IPV and promoting mental health resilience among pregnancy and postpartum women
      in low and lower-middle-income countries.

PMID- 29198413
TI  - Is carotid revascularization worthwhile in patients waiting for kidney
      transplantation?
AB  - Renal failure and haemodialysis are associated with an increased risk of
      cardiovascular disease. Patients undergoing renal transplantation undergo
      rigorous pre-operative vascular assessment, including optimisation of risk
      factors for stroke. The indication for carotid intervention and the threshold for
      carotid endarterectomy in asymptomatic patients with incidental carotid disease
      has not been clarified in the context chronic kidney disease (CKD). This review
      aims to analyse outcomes following carotid endarterectomy in patients with CKD,
      in order to ascertain whether general guidelines for carotid artery
      revascularisation apply to this specific cohort. The current literature suggests
      that outcomes following internal carotid artery (ICA) revascularisation are worse
      in symptomatic and asymptomatic CKD patients compared to the non-CKD population.
      Consequently, asymptomatic patients with renal failure should be managed
      conservatively prior to renal transplantation, whilst those with symptomatic
      disease should be treated according to general guidelines but be informed of
      higher associated risk of stroke and death. Multidisciplinary optimisation
      remains essential in all patients waiting for potential renal transplantation.

PMID- 29198414
TI  - Profiling and determination of phenolic compounds in Indian marketed
      hepatoprotective polyherbal formulations and their comparative evaluation.
AB  - BACKGROUND: Nowadays, plants have been considered as powerful agents for
      treatment of disorders due to their traditional use. Plants have a special role
      in the treatment of various diseases in Ayurveda. Liver disorders with their
      devastating outcomes have been discussed in Ayurveda as well. OBJECTIVES: In the
      present study, polyherbal products (L52 and L38) were retrieved from Ayurveda and
      its pharmacognostic standardization was performed. MATERIALS AND METHODS: Quality
      control test for the Ayurveda tablets were performed as per Indian Pharmacopoeia.
      Dissolution studies of polyherbal Ayurveda marketed formulations were assessed
      based on the phenolic content. Fingerprinting of phytochemical constituents of
      L52 and L38 was performed using spectroscopical (like IR and UV) and
      chromatographic techniques like HPLC, HPTLC and TLC. RESULTS: The results showed
      that L52 and L38 successfully passed quality control tests. Moreover, L52 and L38
      exhibited different pharmacognostic behavior of all herbs present in the product.
      In addition, TLC, IR, HPTLC and HPLC fingerprinting of L52 and L38 demonstrated
      the presence of several phenolic constituents corresponding to the polyherbs.
      CONCLUSION: Regarding the role of phenolic compounds in the treatment of
      hepatitis, L52 and L38 could be appropriate candidates for hepatitis with respect
      to their traditional use in Ayurveda formulation. Moreover, HPTLC and HPLC
      fingerprinting could be utilized as an applicable method for quality control of
      the prepared formulation.

PMID- 29198415
TI  - Effects of dairy manure-derived biochar on psychrophilic, mesophilic and
      thermophilic anaerobic digestions of dairy manure.
AB  - Effects of dairy manure-derived biochar (M-BC) on methane production in anaerobic
      digestion (AD) of dry dairy manure were investigated with three different
      concentrations of biochar (0, 1 and 10 g/L) and temperatures (psychrophilic, 20 
      degrees C; mesophilic, 35  degrees C; thermophilic, 55  degrees C). Compared with
      the AD without any biochar, the cumulative methane and yield in the AD with 10
      g/L biochar were increased to 27.65% and 26.47% in psychrophilic, 32.21% and
      24.90% in mesophilic and 35.71% and 24.69% in thermophilic digestions. The
      addition of M-BC shortened the lag phases of AD at all temperatures in the study
      while it lowered the concentration of total VFAs and propionic acid. It was
      suggested that the high nutrients and alkalinity potential of M-BC (i.e. 9.1% Ca,
      3.6% Mg, 1.3% N, 0.14% P) would play significant roles in enhancing methane
      production and shortening lag phases from the AD of dairy manure.

PMID- 29198416
TI  - Sleep-disordered breathing and epicardial adipose tissue in patients with heart
      failure.
AB  - BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) is common in patients with
      heart failure (HF), contributes to the progression of cardiac disease, and is
      associated with adverse prognosis. Previous evidence indicates that epicardial
      adipose tissue (EAT) is independently associated with sleep apnea in obese
      individuals. We explored the relationship between SDB and EAT in HF patients.
      METHODS AND RESULTS: EAT thickness was assessed by echocardiography in 66
      patients with systolic HF undergoing nocturnal cardiorespiratory monitoring. A
      significantly higher EAT thickness was found in patients with SDB than in those
      without SDB (10.7 +/- 2.8 mm vs. 8.3 +/- 1.8 mm; p = 0.001). Among SDB patients,
      higher EAT thickness was found in both those with prevalent obstructive sleep
      apnea (OSA) and those with prevalent central sleep apnea (CSA). Of interest, EAT
      thickness was significantly higher in CSA than in OSA patients (11.9 +/- 2.9 vs.
      10.1 +/- 2.5 p = 0.022). Circulating plasma norepinephrine levels were higher in
      CSA than in OSA patients (2.19 +/- 1.25 vs. 1.22 +/- 0.92 ng/ml, p = 0.019).
      According to the apnea-hypopnea index (AHI), patients were then stratified in
      three groups of SDB severity: Group 1, mild SDB; Group 2, moderate SDB; Group 3,
      severe SDB. EAT thickness progressively and significantly increased from Group 1
      to Group 3 (ANOVA p < 0.001). At univariate analysis, only left ventricular
      ejection fraction and AHI significantly correlated with EAT (p = 0.019 and p <
      0.0001, respectively). At multivariate analysis, AHI was the only independent
      predictor of EAT (beta = 0.552, p < 0.001). CONCLUSIONS: Our results suggest an
      association between the presence and severity of sleep apneas and cardiac
      visceral adiposity in HF patients.

PMID- 29198417
TI  - The significance of spinal fixation in palliative surgery for spinal metastases.
AB  - The purpose of this study is to assess appropriate fixation methods for surgical
      spinal stabilization for spinal metastases. 191 patients who underwent spine
      surgery for spinal metastases are included in this study. The surgeries included
      1) posterior decompression only (29), 2) posterior decompression and fixation
      (153), and 3) decompression and circumferential fixation (9). We evaluated and
      compared all cases based upon 1) use of fixation, 2) number of levels included in
      the fixation, 3) type of fixation, 4) use of bone graft, 5) presence of
      preoperative collapse of involved vertebrae, and 6) involved area of vertebrae
      according to Kostuik classification. Progression of vertebral collapse on
      radiographs or Magnetic Resonance Imaging (MRI) or occurrence of implant failure
      after surgery was considered a failed case. The number of failed cases was 51
      (27%). The factors that were compared between the failed and successful groups
      were: use of fixation (p < .01), extent of fixation (one level above and one
      level below affected vertebrae vs. ? two above and two below, p < .01), presence
      of preoperative collapse of affected vertebrae (p < .05), and ? four of six
      columns of vertebral involvement according to Kostuik classification (p < .01).
      All results were statistically significant. In conclusion, when treating
      metastatic spinal disease with instability, it is recommended that posterior
      fixation with instrumentation be used and extend at least two levels above and
      two below the affected vertebrae. Preoperative collapse of affected vertebrae and
      greater involvement of the vertebrae with metastatic disease results in greater
      local instability.

PMID- 29198418
TI  - MRI measurements of the normal pediatric optic nerve pathway.
AB  - The purpose of this work is to establish a reference scale of optic nerve pathway
      measurements in pediatric patients according to age using MRI. Optic nerve
      pathway measurements were retrospectively analyzed using an orbits equivalent
      sequence on brain MRI scans of 137 pediatric patients (72 male, 65 female,
      average age = 7.7 years, standard deviation  = 5.3). The examinations were
      performed on a 1.5-T or 3-T Siemens MR system using routine imaging protocols.
      Measurements include diameters of the orbital optic nerves (OON), prechiasmatic
      optic nerves (PON), optic tracts (OT), and optic chiasm (OC). Measurements were
      performed manually by 2 neuroradiologists, using post-processing software.
      Patients were stratified into five age groups for measurement analyses: (I) 0
      1.49 years, (II) 1.5-2.99 years, (III) 3-5.99 years, (IV) 6-11.99 years, and (V)
      12-18 years. The observed value range of OON mean diameter was 2.7 mm
      (Interquartile range (IQR) = 2.4-2.9), PON was 3.2 mm (IQR  =  3.05-3.5), OT 2.6
      mm (IQR = 2-2.9). A strong positive correlation was established between age and
      mean diameter of OON (r = 0.73, p < .001), PON (r = 0.59, p < .001), and OT (r =
      0.72, p < .001). A significant difference in mean OON diameters was found between
      age groups I-II (d = 0.3, p = .01), II-III (d = 0.5, p < .001), III-IV (d = 0.5,
      p < .001) followed by a plateau between IV-V (d = 0.l0, p = .19). OON/OT ratio
      maintained a steady mean value 1 (IQR = 0.93-1.1) regardless of age (p = .7). The
      diameter of optic pathways was found to increase as a function of age with
      consistent positive correlation between nerve and tract for all ages.

PMID- 29198419
TI  - Disruption of the GH receptor gene in adult mice and in insulin sensitive
      tissues.
AB  - To elucidate whether a specific tissue is responsible for the beneficial health
      and longevity phenotype seen in growth hormone (GH) receptor (R) knockout (GHRKO)
      mice, the GHR gene was disrupted specifically in insulin sensitive tissues;
      namely, liver, adipose, and muscle. Furthermore, to investigate if the health-
      and life-span effects seen in the germline GHRKO mice were replicated when GH
      action was ablated after puberty; young, adult onset GHRKO mice were produced and
      characterized. In this review, we summarized the main findings derived from these
      mouse lines.

PMID- 29198420
TI  - Circumportal pancreas - a hazardous anomaly in pancreatic surgery.
AB  - BACKGROUND: Circumportal pancreas (CP) is an anatomical anomaly in the form of
      abnormal parenchymal fusion between the uncinate process and the pancreatic body,
      and it requires an additional parenchymal dissection during
      pancreaticoduodenectomy (PD). This study aimed to investigate the prevalence of
      CP in PD and to evaluate the incidence of postoperative pancreatic fistula (POPF)
      among CP patients. METHODS: Patients who underwent PD from 2002 to 2012 (n = 552)
      were included. Operative records and preoperative images were independently
      reviewed to identify the presence of CP. The incidence of POPF was compared
      between CP and non-CP patients and was evaluated via multivariate analysis.
      RESULTS: CP was confirmed from operative records in 7 (1.3%) patients, and
      abnormal parenchymal fusion was identified from preoperative images in 8 (1.4%)
      patients. The incidence of POPF was significantly higher in CP patients than in
      non-CP patients (71% vs 32%, P = 0.039). On multivariate analysis, CP was an
      independent predictive factor for POPF (odds ratio, 9.97; 95% confidence
      interval, 1.76-56.6; P = 0.009). DISCUSSION: Surgeons should heed the presence of
      CP in PD because this rare anomaly requires an additional parenchymal dissection
      and may increase the incidence of POPF.

PMID- 29198421
TI  - Reply.

PMID- 29198422
TI  - Editorial Comment.

PMID- 29198423
TI  - Fertility protection: complications of surgery and results of removal and
      transplantation of ovarian tissue.
AB  - Fertility-preserving measures are becoming important for patients receiving
      oncological treatment. One method involves cryopreservation of ovarian tissue and
      transplanting it when treatment is completed. We report complications resulting
      from surgical and fertility medicine, and the results of procedures for the
      removal and transplantation of ovarian tissue carried out within the FertiProtekt
      network. A survey using a structured questionnaire was conducted among the
      FertiProtekt network centres between November 2015 and June 2016. The analysis
      included surgical techniques used to remove and transplant ovarian tissue,
      surgical complications and results. Laparoscopic removal and transplantation of
      ovarian tissue have a low risk of complications. Surgical complications occurred
      in three of the network's 1373 ovarian tissue removals (n = 1302) and
      transplantations (n = 71); two complications (0.2%) occurred during removal and
      one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who
      underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of
      transplantations with a follow-up of 6 months or over. Sixteen pregnancies
      occurred in 14 patients, with nine births. The risks and complications of removal
      and transplantation of ovarian tissue are similar to those of standard
      laparoscopy. These procedures are becoming standard for fertility protection in
      cancer patients.

PMID- 29198425
TI  - Providing Care for Lesbian, Gay, Bisexual, and Transgender Immigrants at Health
      Centers and Clinics.

PMID- 29198424
TI  - The uterine fibroid/myoma tumour: analysis of the global research architecture
      using density-equalizing mapping.
AB  - Uterine fibroids can severely impact a woman's quality of life, result in
      significant morbidity and are a leading indication for hysterectomy. Many aspects
      of the disease remain largely obscure. Despite these knowledge gaps, no detailed
      maps of the global fibroid research architecture have yet been generated. This
      study used the NewQIS approach to assess worldwide research productivity,
      encompassing numerous aspects of the scientific output, quality and socioeconomic
      features. Regression analysis indicated an increase in fibroid research activity
      in the investigated time periods. Global research output was dominated by leading
      Western countries, with the USA at the forefront, but also by East Asian
      countries. Socioeconomic benchmarking revealed that Taiwan had the highest
      fibroid research activity per GDP, with a calculated average of 279.46 fibroid
      related publications per 1000 billion USD GDP. Finland was the most active
      country with respect to research activity per population size. Subject area
      analyses revealed major differences in research focuses, for example 'Radiology,
      Nuclear Medicine and Medical Imaging' was assigned to 29.92% of South Korean and
      to only 10.38% of US-American publications. In conclusion, this analysis of
      global fibroid research activity illustrates a multitude of important features
      ranging from quantitative and semi-qualitative fibroid research aspects to
      socioeconomic benchmarking.

PMID- 29198426
TI  - Luliconazole, a new antifungal against Candida species isolated from different
      sources.
AB  - OBJECTIVE: Luliconazole is an inhibitor for sterol 14-alpha-demethylase in fungal
      cells with a broad-spectrum antifungal activity against dermatophytes, Candida
      albicans, Malassezia species, dematiaceous and hyaline hyphomycetes. Furthermore,
      luliconazole has been clinically used for the treatment of pityriasis versicolor,
      dermatophytosis, onychomycosis, cutaneous and mucocutaneous candidiasis. In the
      present study, we aimed to evaluate in vitro antifungal activity of luliconazole
      against several strains of Candida species recovered from different clinical
      materials. MATERIALS AND METHODS: In the present study, 104 strains of Candida
      species including, 34 isolates from vaginitis, 23 isolates from AIDS patients
      with vaginal candidiasis, 24 isolates from neutropenic patients and 24 isolates
      from tracheal tubes, were examined for susceptibility tests. A serial dilution of
      luliconazole (4-0.008MUg/mL) was tested against different strains of Candida
      species recovered from different sources. RESULTS: The minimum inhibitory
      concentration (MIC) range and MIC90 of vaginal isolates (HIV-) were 1-0.063 and
      1MUg/mL. Furthermore, the most of strains (50%) had a MIC of 0.5MUg/mL. The MIC
      ranges were similar (2-0.016MUg/mL) for both vaginal (HIV+) and neutropenic
      patients isolates, whereas, MIC90 for them were 0.5 and 1MUg/mL, respectively.
      All tracheal tubes strains were inhibited at the range of 2-0.008MUg/mL with
      MIC90=1MUg/mL. Totally, the lowest MIC50 (MIC=0.015MUg/mL), MIC90 (MIC=1MUg/mL)
      and MICGM (MIC=0.05MUg/mL) are correlated to C. glabrata, a non-albicans species.
      CONCLUSION: It is concluded that, luliconazole could be an alternative anti
      Candida agent, however, in vivo studies must be confirmed usefulness of drug for
      clinical usage.

PMID- 29198427
TI  - Towards the identification of ancestrally shared regenerative mechanisms across
      the Metazoa: A Transcriptomic case study in the Demosponge Halisarca caerulea.
AB  - Regeneration is an essential process for all multicellular organisms, allowing
      them to recover effectively from internal and external injury. This process has
      been studied extensively in a medical context in vertebrates, with pathways often
      investigated mechanistically, both to derive increased understanding and as
      potential drug targets for therapy. Several species from other parts of the
      metazoan tree of life, including Hydra, planarians and echinoderms, noted for
      their regenerative capabilities, have previously been targeted for study. Less
      well-documented for their regenerative abilities are sponges. This is surprising,
      as they are both one of the earliest-branching extant metazoan phyla on Earth,
      and are rapidly able to respond to injury. Their sessile lifestyle, lack of an
      external protective layer, inability to respond to predation and filter-feeding
      strategy all mean that regeneration is often required. In particular the
      demosponge genus Halisarca has been noted for its fast cell turnover and ability
      to quickly adjust its cell kinetic properties to repair damage through
      regeneration. However, while the rate and structure of regeneration in sponges
      has begun to be investigated, the molecular mechanisms behind this ability are
      yet to be catalogued. Here we describe the assembly of a reference transcriptome
      for Halisarca caerulea, along with additional transcriptomes noting response to
      injury before, shortly following (2h post-), and 12h after trauma. RNAseq reads
      were assembled using Trinity, annotated, and samples compared, to allow initial
      insight into the transcriptomic basis of sponge regenerative processes. These
      resources are deep, with our reference assembly containing >92.6% of the BUSCO
      Metazoa set of genes, and well-assembled (N50s of 836, 957, 1688 and 2032 for
      untreated, 2h, 12h and reference transcriptomes respectively), and therefore
      represent excellent qualitative resources as a bedrock for future study. The
      generation of transcriptomic resources from sponges before and following
      deliberate damage has allowed us to study particular pathways within this species
      responsible for repairing damage. We note particularly the involvement of the Wnt
      cascades in this process in this species, and detail the contents of this
      cascade, along with cell cycle, extracellular matrix and apoptosis-linked genes
      in this work. This resource represents an initial starting point for the
      continued development of this knowledge, given H. caerulea's ability to
      regenerate and position as an outgroup for comparing the process of regeneration
      across metazoan lineages. With this resource in place, we can begin to infer the
      regenerative capacity of the common ancestor of all extant animal life, and
      unravel the elements of regeneration in an often-overlooked clade.

PMID- 29198429
TI  - My Odyssey Through the Changing World of Mental Health.

PMID- 29198428
TI  - Corrigendum to 'Antimicrobial susceptibility of pathogens isolated from surgical
      site infections in Japan: Comparison of data from nationwide surveillance studies
      conducted in 2010 and 2014-2015' [J Infect Chemother 23 (2017) 339-348].

PMID- 29198430
TI  - Correlation between mandibular bone density and skeletal bone density in a
      Catalonian postmenopausal population.
AB  - OBJECTIVES: The aim of this study was to determine if the mandible (MD)
      experiences reductions in bone mineral density (BMD) similar to the lumbar spine
      (LS) and femoral neck (FN) in a postmenopausal population. STUDY DESIGN: A total
      of 137 postmenopausal women underwent 3 types of densitometric examinations: LS,
      FN, and MD as measured in 3 regions (MD-R1, MD-R2, and MD-R3), as well as the
      entire mandible (MD-Net) using a dual photon bone X-ray densitometer.
      Densitometry of the LS and FN were performed according to the protocol of the
      International Society for Clinical Densitometry. Mandibular densitometry was
      performed using a modification of a previous technique, placing the patient in
      the left lateral decubitus position, with the head supported by a 13-cm-thick
      cushion above the temporomandibular joint. RESULTS: Significant correlations were
      found between densitometry results for the LS and the MD, with P values of .021
      at MD-R1 (ramus); .001 at MD-R2 (body); .050 at MD-R3 (symphysis), and .001 at MD
      Net (total mandibular density). No correlation was found between mandibular and
      FN densitometry (P > .05). CONCLUSIONS: According to the results, for this
      population, it can be affirmed that the MD responds to osteoporosis in ways
      similar to the LS.

PMID- 29198432
TI  - 2017 ESC Guidelines for the management of acute myocardial infarction in patients
      presenting with ST-segment elevation.

PMID- 29198431
TI  - Comments on the 2017 ESC Guidelines for the Management of Acute Myocardial
      Infarction in Patients Presenting With ST-segment Elevation.

PMID- 29198435
TI  - Modifications of serum levels of omentin-1 and other cardiovascular risk factors
      following weight loss secondary to a Mediterranean hypocaloric diet.
AB  - BACKGROUND & AIMS: Omentin-1 might play a role on insulin resistance,
      dyslipidemia and obesity. The aim of this investigation was to evaluate the
      influence of weight loss on omentin-1 concentrations after a hypocaloric diet
      with Mediterranean pattern. METHODS: A Caucasian sample of 67 obese patients was
      analyzed before and after 3 months on a hypocaloric diet. Anthropometric
      parameters, blood pressure, fasting blood glucose, C-reactive protein (CRP),
      fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1
      were measured. RESULTS: Sixty-seven obese subjects were enrolled in the study.
      The mean age was 48.3 +/- 8.0 years (range: 25-66) and the mean BMI 34.5 +/- 4.8
      kg/m2 (range: 30.2-40.8). Gender distribution was 50 females (74.6%) and 17 males
      (25.4%). After dietary intervention and in males and females; body mass index,
      weight, fat mass, waist circumference, blood pressure, glucose, LDL cholesterol,
      insulin and HOMA-IR decreased. Omentin-1 levels increase after dietary
      intervention (males vs females) (delta basal vs 3 months: 10.0 +/- 3.8 ng/dl: p =
      0.01 vs 9.9 +/- 4.1 ng/dl; p = 0.03). In the multiple regression analysis
      adjusted for age and sex; BMI and insulin remained independently associated with
      baseline and post-treatment levels of omentin-1. CONCLUSIONS: Our investigation
      showed a significant increase in omentin-1 levels after weight loss secondary to
      a hypocaloric diet with a Mediterranean pattern.

PMID- 29198436
TI  - Reprogramming Tumor Blood Vessels for Enhancing Immunotherapy.
AB  - Angiogenic blood vessels contribute to generating an immunosuppressive tumor
      microenvironment, in part by limiting the extravasation of T cells. Functional
      reprogramming of angiogenic blood vessels, for example through angiopoietin-2
      blockade, may improve T cell trafficking in tumors and the efficacy of immune
      checkpoint blockade (ICB) and other cancer immunotherapies.

PMID- 29198437
TI  - Spinal Cord Injuries and Nerve Dependence in Prostate Cancer.
AB  - Nerves are emerging as drivers of tumorigenesis, as demonstrated in the mouse
      where denervation suppresses prostate cancer; however, clinical evidence is
      needed. Patients with spinal cord injuries (SCIs) resulting in functional
      denervation of the prostate have a lower incidence of prostate cancer. This may
      constitute a clinical evidence for nerve dependence in human prostate
      tumorigenesis.

PMID- 29198438
TI  - Targeting Oncogenic Transcription Factors: Therapeutic Implications of Endogenous
      STAT Inhibitors.
AB  - Misregulation of transcription factors, including signal transducer and activator
      of transcription (STAT) proteins, leads to inappropriate gene expression patterns
      that can promote tumor initiation and progression. Under physiologic conditions,
      STAT signaling is stimulus dependent and tightly regulated by endogenous
      inhibitors, namely, suppressor of cytokine signaling (SOCS) proteins,
      phosphatases, and protein inhibitor of activated STAT (PIAS) proteins. However,
      in tumorigenesis, STAT proteins become constitutively active and promote the
      expression of progrowth and prosurvival genes. Although STAT activation has been
      widely implicated in cancer, therapeutic STAT inhibitors are still largely absent
      from the clinic. This review dissects the mechanisms of action of two families of
      endogenous STAT inhibitors, the SOCS and PIAS families, to potentially inform the
      development of novel therapeutic inhibitors.

PMID- 29198439
TI  - Mitochondrial Transfer in the Leukemia Microenvironment.
AB  - The bone marrow microenvironment (BMME) is a complex ecosystem that instructs and
      protects hematopoietic stem cells (HSCs) and their malignant counterparts, the
      leukemia-initiating cells (LICs). Within the physical and functional crosstalk
      that takes place between HSCs, LICs, and the BMME, the transfer of organelles and
      of mitochondria in particular is an important new intercellular communication
      mode in addition to adhesion molecules, tunneling nanotubes (TNTs), and the
      paracrine secretion of cytokines, (onco)metabolites, and extracellular vesicles
      (EVs). In this review we discuss the functional roles of mitochondrial transfer
      between BMME and leukemic cells, and give insights into this new mechanism of
      drug resistance whose understanding will open the way to innovative anticancer
      adjuvant treatments.

PMID- 29198440
TI  - Fanconi Anemia Signaling and Cancer.
AB  - The extremely high cancer incidence associated with patients suffering from a
      rare human genetic disease, Fanconi anemia (FA), demonstrates the importance of
      FA genes. Over the course of human tumor development, FA genes perform critical
      tumor-suppression roles. In doing so, FA provides researchers with a unique
      genetic model system to study cancer etiology. Here, we review how aberrant
      function of the 22 FA genes and their signaling network contributes to
      malignancy. From this perspective, we will also discuss how the knowledge
      discovered from FA research serves basic and translational cancer research.

PMID- 29198441
TI  - Mitochondria, Bioenergetics and Apoptosis in Cancer.
AB  - Until recently, the dual roles of mitochondria in ATP production (bioenergetics)
      and apoptosis (cell life/death decision) were thought to be separate. New
      evidence points to a more intimate link between these two functions, mediated by
      the remodeling of the mitochondrial ultrastructure during apoptosis. While most
      of the key molecular players that regulate this process have been identified
      (primarily membrane proteins), the exact mechanisms by which they function are
      not yet understood. Because resistance to apoptosis is a hallmark of cancer, and
      because ultimately all chemotherapies are believed to result directly or
      indirectly in induction of apoptosis, a better understanding of the biophysical
      processes involved may lead to new avenues for therapy.

PMID- 29198443
TI  - How the human brain introspects about one's own episodes of cognitive control.
AB  - Metacognition refers to our capacity to reflect upon our experiences, thoughts
      and actions. Metacognition processes are linked to cognitive control functions
      that allow keeping our actions on-task. But it is unclear how the human brain
      builds an internal model of one's cognition and behaviour. We conducted two
      functional magnetic resonance imaging (fMRI) experiments in which brain activity
      was recorded 'online' as participants engaged in a memory-guided search task and
      then later 'offline' when participants introspected about their prior experience
      and cognitive states during performance. In Experiment 1 the memory cues were
      task-relevant while in Experiment 2 they were irrelevant. Across Experiments, the
      patterns of brain activity, including frontoparietal regions, were similar during
      on-task and introspection states. However the connectivity profile amongst
      frontoparietal areas was distinct during introspection and modulated by the
      relevance of the memory cues. Introspection was also characterized by increased
      temporal correlation between the default-mode network (DMN), frontoparietal and
      dorsal attention networks and visual cortex. We suggest that memories of one's
      own experience during task performance are encoded in large-scale patterns of
      brain activity and that coupling between DMN and frontoparietal control networks
      may be crucial to build an internal model of one's behavioural performance.

PMID- 29198442
TI  - Biology Informs Treatment Choices in Diffuse Large B Cell Lymphoma.
AB  - The effective deployment of rationally developed therapies for diffuse large B
      cell lymphoma (DLBCL) requires rapid assimilation of new biological data. Within
      this framework, here we address topical issues at the intersection of DLBCL
      biology and the clinic. We discuss targeting of B cell receptor (BCR) signaling,
      with emphasis on identifying patients who may benefit from this maneuver and how
      to best achieve it. We address strategies to modulate the DLBCL microenvironment,
      including the use of immune checkpoint inhibitors in selected DLBCL subsets, and
      the potential activity of alternative antiangiogenic therapies. Lastly, we
      highlight the emerging recognition of MYC and BCL2 coexpression as the most
      robust predictor of DLBCL outcome, and discuss rationally conceived experimental
      approaches to treat these high-risk patients.

PMID- 29198445
TI  - A deep dive into the left ventricle.

PMID- 29198444
TI  - Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis.
AB  - CONTEXT: Diabetes insipidus (DI) is one of most common complications of
      Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary
      deficiencies and metabolic alterations have not been clearly defined yet.
      OBJECTIVES: Evaluate prevalence of endocrine and metabolic manifestations in a
      cohort of patients affected by Pulmonary LCH. METHODS: Observational cross
      sectional study on 18 adults (7 M/11 F, 42+/-12years) studied for complete basal
      and dynamic endocrine lab tests and glucose metabolism. RESULTS: Hypothalamic
      pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth
      Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1
      central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found
      in 2 patients each. All these central endocrine alterations were always
      associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence
      of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39%
      and 33%, higher than expected basing on epidemiological data on general Italian
      population. Multi-system-LCH without risk-organ involvement (LCH MS-RO-) seems to
      have slightly higher prevalence of insulin resistance, glucose alterations and
      metabolic syndrome than LCH with isolated lung involvement (LCH SS lung+). A
      papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient.
      CONCLUSIONS: The presence of anterior pituitary deficiencies should be
      systematically sought in all LCH patients with DI both at diagnosis and during
      the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary
      LCH, particularly those with MS disease, have a worse metabolic profile than
      general population. Occurrence of papillary thyroid carcinoma has been reported.

PMID- 29198446
TI  - Targeted profiling of hydrophilic constituents of royal jelly by hydrophilic
      interaction liquid chromatography-tandem mass spectrometry.
AB  - In the present work a Hydrophilic Interaction Liquid Chromatography-tandem Mass
      Spectrometry (HILIC-MS/MS) method was developed for the efficient separation and
      quantification of a large number of small polar bioactive molecules in Royal
      Jelly. The method was validated and provided satisfactory detection sensitivity
      for 88 components. Quantification was proven to be precise for 64 components
      exhibiting good linearity, recoveries R% >90% for the majority of analytes and
      intra- and inter-day precision from 0.14 to 20% RSD. Analysis of 125 fresh royal
      jelly samples of Greek origin provided useful information on royal jelly's
      hydrophilic bioactive components revealing lysine, ribose, proline, melezitose
      and glutamic acid to be in high abundance. In addition the occurrence of 18
      hydrophilic nutrients which have not been reported previously as royal jelly
      constituents is shown.

PMID- 29198447
TI  - Fabrication and evaluation of magnetic phosphodiesterase-5 linked nanoparticles
      as adsorbent for magnetic dispersive solid-phase extraction of inhibitors from
      Chinese herbal medicine prior to ultra-high performance liquid chromatography
      quadrupole time-of-flight mass spectrometry analysis.
AB  - In the present study, the preparation of the magnetic phosphodiesterase-5 linked
      Fe3O4@ SiO2 nanoparticles was successfully achieved by amide reaction and the
      magnetic phosphodiesterase-5 linked Fe3O4@SiO2 nanoparticles were evaluated as a
      new adsorbent for magnetic dispersive solid-phase extraction of ligands from
      medicinal plant samples before the analysis by UHPLC-Q-TOF/MS. The prepared
      phosphodiesterase-5 linked Fe3O4@SiO2 nanoparticles were characterized by X-ray
      diffraction, Fourier transform infrared spectroscopy, transmission electron
      microscopy, vibration sample magnetometer and potential laser particle size
      analyzer. The effects of EDC concentration, incubation time and bead-protein
      ratio on the amount of immobilized protein were studied. The main experimental
      parameters affect extraction efficiency of ligands, such as wash times, wash
      solvents, incubation pH, ion strength and incubation temperature, were
      investigated and optimized by using echinacoside as a model compound. The
      absolute recovery of echinacoside was ranged from 98.36%-102.16% in Cistanche
      tubulosa sample under the optimal extraction conditions. Good linearity was
      observed in the investigated concentration range of 0.006 mgmL-1-0.97 mgmL-1(R2 =
      0.9999). The limit of detection was 0.002 mgmL-1. The RSDs of within-day and
      between-day precision were less than 2.3%. Due to the excellent magnetic behavior
      of Fe3O4@SiO2 nanoparticles, the proposed method was shown to be simple and
      rapid. Remarkably, the magnetic phosphodiesterase-5 linked Fe3O4@SiO2
      nanoparticles could be recycled for ten times with loss of 10% activity.

PMID- 29198448
TI  - Lithium, magnesium and sulfur purification from seawater using an ion
      chromatograph with a fraction collector system for stable isotope measurements.
AB  - We describe the mass descrimination and validation of an offline method for
      purification of Li, Mg and S with an ion chromatograph coupled to an automated
      fraction collector for use prior to stable isotope measurements. Significant sub
      fraction mass fractionation was observed for both the Li and the Mg stable
      isotope ratios. The lighter Li and heavier Mg isotopes were preferentially
      retained by the column, resulting in 7Li/6Li and 26Mg/24Mg biases up to 85.80/00
      and 0.950/00, respectively. The isotopic compositions of Li, Mg, and S separated
      from seawater were delta7LiL-SVEC = +30.90/00, delta26MgDSM3 = -0.83 +/-
      0.100/00, and delta34SVCDT = +19.4 +/- 0.60/00; each chromatographic peak was
      completely recovered, and the results were in good agreement with the published
      values regardless of whether or not chemical suppressor was used. The
      purification method enables multi-isotope analysis of a sample using various mass
      spectrometry techniques, such as multiple-collector inductively coupled plasma
      and thermal ionization mass spectrometry.

PMID- 29198449
TI  - Effects of Flibanserin on the Pharmacokinetics of a Combined
      Ethinylestradiol/Levonorgestrel Oral Contraceptive in Healthy Premenopausal
      Women: A Randomized Crossover Study.
AB  - PURPOSE: This study aimed to investigate the effect of steady-state exposure to
      flibanserin, a 5-HT1A agonist/5-HT2A antagonist approved for the treatment of
      hypoactive sexual desire disorder in premenopausal women, on the single-dose
      pharmacokinetics of the contraceptive steroids ethinylestradiol and
      levonorgestrel in healthy premenopausal women. METHODS: Healthy female volunteers
      (N = 24) received 2 single doses of a combined oral contraceptive containing
      ethinylestradiol 30 MUg and levonorgestrel 150 MUg, either alone (reference) or
      preceded by treatment with flibanserin 100 mg once daily for 14 days (test). The
      2 treatments were given in randomized order, with a 4-week washout period
      following the last administration of the first treatment. Plasma concentrations
      of ethinylestradiol and levonorgestrel were measured over 48 hours after dosing
      for the determination of pharmacokinetic parameters; the primary end points were
      Cmax and AUC0-infinity of ethinylestradiol and levonorgestrel. FINDINGS: Of the
      24 women enrolled (mean age, 38.0 years), 23 completed the study. Mean (SD) Cmax
      and AUC0-infinity values of ethinylestradiol were 66.7 (16.3) pg/mL and 693 (268)
      pg . h/mL, respectively, following the oral contraceptive alone, and 72.7 (25.5)
      pg/mL and 740 (235) pg . h/mL, respectively, when the oral contraceptive was
      preceded by flibanserin. In both cases, the 90% CIs of the reference/test ratios
      of Cmax and AUC0-infinity were within the range of 80% to 125%, indicating that
      flibanserin had no significant effect on the pharmacokinetic properties of
      ethinylestradiol. Similarly, the mean (SD) Cmax and AUC0-infinity values of
      levonorgestrel were 5.0 (1.6) ng/mL and 52.2 (18.7) ng . h/mL, respectively, with
      the oral contraceptive alone, and 5.0 (1.6) ng/mL and 53.3 (20.4) ng . h/mL,
      respectively, following flibanserin; again, in both cases, the 90% CIs of the
      reference/test ratios were within the range of 80% to 125%, indicating that
      flibanserin had no significant effect on the pharmacokinetic properties of
      levonorgestrel. All adverse events were mild to moderate in intensity (incidence:
      12.5% and 70.8% with ethinylestradiol/levonorgestrel treatment alone and
      following administration of flibanserin, respectively). IMPLICATIONS:
      Pretreatment with flibanserin 100 mg once daily for 2 weeks did not produce a
      clinically relevant change in oral contraceptive drug exposure following single
      dose administration of ethinylestradiol/levonorgestrel. This finding is relevant
      to women with hypoactive sexual desire disorder who might prefer oral
      contraceptives to other forms of birth control. EudraCT No: 2006-006960-46.

PMID- 29198451
TI  - Development of Microbiota in Infants and its Role in Maturation of Gut Mucosa and
      Immune System.
AB  - Dysbiosis of the gut microbiota has been associated with increasing numbers of
      diseases, including obesity, diabetes, inflammatory bowel disease, asthma,
      allergy, cancer and even neurologic or behavioral disorders. The other side of
      the coin is that a healthy microbiota leads to a healthy human development, to a
      mature and well trained immune system and to an efficient metabolic machinery.
      What we have learned in adults is in the end the result of a good start, a
      programmed, healthy development of the microbiota that must occur in the early
      years of life, probably even starting during the fetal stage. This review aims to
      present and discuss reports that helps us understand what we have learned of the
      development of microbiota during the early times of life, from pregnancy to
      delivery to the early years after birth. The impact of the establishment of
      "healthy" bacterial communities on human surfaces in the maturation of epithelia,
      immune system and metabolism will also be discussed. The right process of
      maturation of the bacterial communities that establish a symbiosis with human
      surfaces depends on a number of environmental, genetic and temporal factors that
      need to be understand in order to have tools to monitor a healthy development and
      eventually intervene to correct undesired courses.

PMID- 29198450
TI  - Effects of Exercise on Non-motor Symptoms in Parkinson's Disease.
AB  - Patients with Parkinson's disease experience disabling non-motor symptoms,
      including autonomic dysfunction, cognitive decline, and sleep disorders.
      Pharmacologic treatments for these symptoms are often ineffective or have
      intolerable side effects. Therefore, non-pharmacologic interventions are an
      attractive alternative. Exercise in particular has the potential to alleviate the
      progressive impairment related to these non-motor symptoms. In this commentary,
      we explore available research that addresses the impact of exercise and physical
      activity on autonomic dysfunction, cognitive impairment, and sleep disorders in
      Parkinson's disease and suggest areas in need of further study. Many gaps remain
      in our understanding of the most effective exercise intervention for these
      symptoms, the mechanisms underlying exercise-induced changes, and the best way to
      monitor response to therapy. However, available research suggests that exercise
      is a promising approach to improve non-motor symptoms in patients with
      Parkinson's disease.

PMID- 29198452
TI  - Betaglycan (TGFBR3) up-regulation correlates with increased TGF-beta signaling in
      Marfan patient fibroblasts in vitro.
AB  - BACKGROUND: Marfan syndrome (MFS), a congenital connective tissue disorder
      leading to aortic aneurysm development, is caused by fibrillin-1 (FBN1) gene
      mutations. Transforming growth factor beta (TGF-beta) might play a role in the
      pathogenesis. It is still a matter of discussion if and how TGF-beta up-regulates
      the intracellular downstream pathway, although TGF-beta receptor 3 (TGFBR3 or
      Betaglycan) is thought to be involved. We aimed to elucidate the role of TGFBR3
      protein in TGF-beta signaling in Marfan patients. METHODS: Dermal fibroblasts of
      MFS patients with haploinsufficient (HI; n=9) or dominant negative (DN; n=4) FBN1
      gene mutations, leading to insufficient or malfunctioning fibrillin-1,
      respectively, were used. Control cells (n=10) were from healthy volunteers. We
      quantified TGFBR3 protein expression by immunofluorescence microscopy and gene
      expression of FBN1, TGFB1, its receptors, and downstream transcriptional target
      genes by quantitative polymerase chain reaction. RESULTS: Betaglycan protein
      expression in FBN1 mutants pooled was higher than in controls (P=.004) and in DN
      higher than in HI (P=.015). In DN, significantly higher mRNA expression of FBN1
      (P=.014), SMAD7 (P=.019), HSP47 (P=.023), and SERPINE1 (P=.008), but a lower
      HSPA5 expression (P=.029), was observed than in HI. A pattern of higher
      expression was noted for TGFB1 (P=.059), FN1 (P=.089), and COL1A1 (P=.089) in DN
      as compared to HI. TGFBR3 protein expression in cells, both presence in the
      endoplasmic reticulum and amount of vesicles per cell, correlated positively with
      TGFB1 mRNA expression (Rs=0.60, P=.017; Rs=0.55, P=.029; respectively). TGFBR3
      gene expression did not differ between groups. CONCLUSION: We demonstrated that
      activation of TGF-beta signaling is higher in patients with a DN than an HI FBN1
      gene mutation. Also, TGFBR3 protein expression is increased in the DN group and
      correlates positively with TGFB1 expression in groups pooled. We suggest that
      TGFBR3 protein expression is involved in up-regulated TGF-beta signaling in MFS
      patients with a DN FBN1 gene mutation.

PMID- 29198453
TI  - Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene
      adequacy in haemodialysis-associated restless legs syndrome.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterised
      by bothersome symptoms associated with impaired quality of life and sleep
      hygiene. Rotigotine is a novel therapeutic alternative, although few studies have
      been published in patients on haemodialysis (HD) with RLS treated with
      rotigotine. OBJECTIVES: 1.- To establish the prevalence of RLS in our HD unit. 2.
      To evaluate the efficacy and safety profile of rotigotine and its effect on
      symptoms, quality of life and sleep hygiene in our HD population with RLS.
      MATERIAL AND METHODS: A single-centre, 12-week prospective study. Two stages (6
      weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analysed: 1.-
      Demographic data, biochemistry data, HD suitability parameters and RLS medical
      treatment data. 2.- Lower extremity symptoms questionnaire (QS). 3.- RLS severity
      symptoms scale (SRLSS). 4.- RLS Quality of life: John Hopkins RLS-QoL (JH-QoL).
      5.- Sleep hygiene: SCOPA Scale. RESULTS: We included 66 HD patients, 14 with RLS;
      44.4% male, 70.2+/-9.9 years and 111.1+/-160.8 months on HD. And 22.9% RLS.
      Exclusively in stage 2, a significant improvement for QS (10+/-2.4 vs. 5.7+/
      1.0), SRLSS (21+/-4 vs. 5.7+/-4.6), JH-QoL (22.1+/-4.4 vs. 4.3+/-4.0) and SCOPA
      (16+/-5.3 vs. 6.7+/-1.9) were observed. A 77.7 and 11.1%, showed partial (> 20%)
      and complete (> 80%) remission, respectively, while 55.5% achieved "zero"
      symptoms. Only one patient had gastrointestinal intolerance and none experienced
      augmentation effect. No changes in biochemical data, suitability for dialysis or
      medical treatment were found. The inter-group analysis showed a significant
      improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. CONCLUSIONS:
      RLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical
      symptoms, quality of life and sleep hygiene in RLS patients on HD and was found
      to be a safe drug with minimal side effects and total therapeutic compliance.
      Nevertheless, future studies should be performed to confirm the benefits of
      rotigotine in RLS patients on haemodialysis.

PMID- 29198454
TI  - Polarity Sorting of Microtubules in the Axon.
AB  - A longstanding question in cellular neuroscience is how microtubules in the axon
      become organized with their plus ends out, a pattern starkly different from the
      mixed orientation of microtubules in vertebrate dendrites. Recent attention has
      focused on a mechanism called polarity sorting, in which microtubules of opposite
      orientation are spatially separated by molecular motor proteins. Here we discuss
      this mechanism, and conclude that microtubules are polarity sorted in the axon by
      cytoplasmic dynein but that additional factors are also needed. In particular,
      computational modeling and experimental evidence suggest that static crosslinking
      proteins are required to appropriately restrict microtubule movements so that
      polarity sorting by cytoplasmic dynein can occur in a manner unimpeded by other
      motor proteins.

PMID- 29198455
TI  - Bovine respiratory syncytial virus seroprevalence and risk factors in feedlot
      cattle from Cordoba and Santa Fe, Argentina.
AB  - Bovine respiratory syncytial virus (BRSV) is one of the causative agents of
      respiratory disease in cattle all over the world, leading to important economic
      losses. The aim of this work was to determine the seroprevalence of BRSV in
      feedlot cattle of Argentina and the risk factors associated with the disease.
      Results showed a high individual seroprevalence of 78.64% (95% confidence
      interval adjusted [CI]=66.55-90.75%) against the virus. Positive association was
      found between the presence of high BRSV neutralizing antibody titers, and the
      following risk factors: cattle age, source of animals, presence of clinical
      respiratory signs and herd size. This work contributes to updating the
      understanding of its epidemiology in Argentinean feedlots and poses the need for
      reevaluating vaccination strategies against this virus in order to control
      infection and its impact on productivity.

PMID- 29198457
TI  - Instantaneous Wave-Free Ratio Outcomes and the Epistemology of Ischemia.

PMID- 29198456
TI  - First-in-Man Fully Percutaneous Complete Bypass of Heart and Lung.

PMID- 29198458
TI  - Clinical Outcomes According to Fractional Flow Reserve or Instantaneous Wave-Free
      Ratio in Deferred Lesions.
AB  - OBJECTIVES: The authors investigated 2-year clinical outcomes according to
      fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) values in
      deferred lesions. BACKGROUND: Invasive physiological indices such as FFR or iFR
      are used in clinical practice to select ischemia-causing stenosis and to guide
      the treatment strategy for patients with coronary artery disease. METHODS: From
      the 3V FFR-FRIENDS (3-Vessel Fractional Flow Reserve for the Assessment of Total
      Stenosis Burden and Its Clinical Impact in Patients With Coronary Artery Disease)
      study, 821 deferred lesions (n = 374) with both FFR and iFR available were
      included in this study. The primary outcome was major adverse cardiac events
      (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven
      revascularization) at 2 years. The lesions were classified according to FFR and
      iFR cutpoints into concordant normal (Group 1: FFR >0.80 and iFR >0.89), high FFR
      and low iFR (Group 2: FFR >0.80 and iFR <=0.89), low FFR and high iFR (Group 3:
      FFR <=0.80 and iFR >0.89), and concordant abnormal (Group 4: FFR <=0.80 and iFR
      <=0.89). RESULTS: Deferred lesions with low FFR (<=0.80) or low iFR (<=0.89)
      showed significantly higher rates of 2-year MACE, compared with high FFR (>0.80)
      or high iFR (>0.89), respectively (7.2% in low FFR vs. 2.4% in high FFR; p <
      0.001; 8.1% in low iFR vs. 2.4% in high iFR; p < 0.001). Both FFR and iFR showed
      significant association with occurrence of MACE as continuous values (hazard
      ratio [HR] of FFR: 0.570, 95% confidence interval [CI]: 0.337 to 0.963; p <
      0.001; HR of iFR: 0.350, 95% CI: 0.217 to 0.567; p < 0.001). When comparing the
      discriminant ability between FFR and iFR, the c-index was comparable between FFR
      and iFR (c-index 0.677 vs. 0.685; p = 0.857). Among 4 groups classified according
      to FFR and iFR levels, only Group 4 with concordant abnormal results showed
      significantly higher risk of MACE, compared with group 1 (HR: 7.708, 95% CI:
      2.621 to 22.667; p < 0.001). CONCLUSIONS: Both FFR and iFR showed significant
      association with future risk of MACE in deferred lesions. The discordant results
      between FFR and iFR were not associated with the increased risk of MACE. The risk
      of MACE was significantly increased only in lesions with abnormal results of both
      FFR and iFR.

PMID- 29198459
TI  - How and When to Evaluate Nonculprit Lesions in ST-Segment Elevation Myocardial
      Infarction.

PMID- 29198460
TI  - Combined Transcatheter Treatment of Ventricular Septal Rupture and Mitral
      Regurgitation After an Acute Myocardial Infarction.

PMID- 29198461
TI  - Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients
      With ST-Segment Elevation Myocardial Infarction.
AB  - OBJECTIVES: The aim of this study was to examine the level of agreement between
      acute instantaneous wave-free ratio (iFR) measured across nonculprit stenoses in
      patients with ST-segment elevation myocardial infarction (STEMI) and iFR measured
      at a staged follow-up procedure. BACKGROUND: Acute full revascularization of
      nonculprit stenoses in STEMI is debated and currently guided by angiography.
      Acute functional assessment of nonculprit stenoses may be considered. METHODS:
      Immediately after successful primary culprit intervention for STEMI, nonculprit
      coronary stenoses were evaluated with iFR and left untreated. Follow-up
      evaluation with iFR was performed at a later stage. iFR <0.90 was considered
      hemodynamically significant. RESULTS: One hundred twenty patients with 157
      nonculprit lesions were included. Median acute iFR was 0.89 (interquartile range
      [IQR]: 0.82 to 0.94; n = 156), and median follow-up iFR was 0.91 (interquartile
      range: 0.86 to 0.96; n = 147). Classification agreement was 78% between acute and
      follow-up iFR. The negative predictive value of acute iFR was 89%. Median time
      from acute to follow-up evaluation was 16 days (IQR: 5 to 32 days). With follow
      up within 5 days after STEMI, no difference was observed between acute and follow
      up iFR, and classification agreement was 89%. With follow-up >=16 days after
      STEMI, acute iFR was lower than follow-up iFR, and classification agreement was
      70%. CONCLUSIONS: Acute iFR evaluation appeared valid for ruling out significant
      nonculprit stenoses in patients with STEMI undergoing primary percutaneous
      coronary intervention. The time interval from acute to follow-up iFR influenced
      classification agreement, suggesting that inherent physiological disarrangements
      during STEMI may contribute to classification disagreement.

PMID- 29198462
TI  - The Relationship Between Automated Office and Awake Ambulatory Blood Pressure May
      Be Different at Thresholds for Diagnosis and Target for Therapy.

PMID- 29198463
TI  - Comparability of Automated Office Blood Pressure to Daytime 24-Hour Ambulatory
      Blood Pressure.
AB  - BACKGROUND: Clinical practice guidelines endorse automated office blood pressure
      (AOBP) measurement as the preferred in-office measurement modality. However,
      recent data indicate that this method may underestimate daytime ambulatory BP.
      The objective of this study was to further assess the comparability of mean AOBP
      and daytime ambulatory BP in clinical practice. METHODS: A retrospective cross
      sectional chart review was conducted of 96 consecutive patients referred from
      primary or specialty care practices to a tertiary care ambulatory BP monitoring
      service. Six AOBP readings were taken using an appropriately cuffed BpTRU (BpTRU
      Medical Devices, Coquitlam, Canada) device on the nondominant arm and no rest
      period (first reading discarded). Twenty-four-hour ambulatory BP monitoring was
      then performed. Between-group means were compared with paired t tests. The
      proportion of patients with differences of >= 5, 10, and 15 mm Hg was tabulated.
      RESULTS: Mean age was 52.6 +/- 16.7 years, 60% were women, and 79% had previously
      diagnosed hypertension. Mean AOBPs were 130.8 +/- 15.5/82.3 +/- 10.7 mm Hg, and
      mean daytime ambulatory BPs were 142.8 +/- 14.9/83.9 +/- 11.2 mm Hg (difference
      of -11.9 +/- 13.5/-1.6 +/- 7.6; P < 0.001 for systolic BP and P < 0.04 for
      diastolic BP). Between-group differences were greater in patients with previous
      hypertension and in those with daytime ambulatory BP levels >= 135 mm Hg. The
      proportions of patients with systolic or diastolic BP differences of >= 5, 10 and
      15 mm Hg were 89%, 52%, and 33%, respectively. CONCLUSIONS: Mean AOBP
      underestimates daytime ambulatory BP. Variability between the 2 methods is high.
      These findings do not support the premise that AOBP closely approximates daytime
      ambulatory BP.

PMID- 29198464
TI  - Corrigendum to "Trends in insurance coverage and treatment among persons with
      opioid use disorders following the affordable care act" [Drug Alcohol. Depend.
      179 (2017) 271-274].

PMID- 29198465
TI  - Linear sound attenuation model for assessing external stimuli in prenatal period.
AB  - The popularization of acoustic stimulation during the prenatal period encourages
      the analysis of sounds reaching the inside of the uterus. To assess the
      distortion of any sound stimuli, a mathematical model of attenuation has to be
      used. In this paper a mathematical model is proposed on the basis of data from a
      physical model. The physical model consisted of muscle slices of two different
      thicknesses placed in a tank filled with water. The amplitudes of sinusoidal
      waves between 160 and 2000 Hz were measured under the water surface. Using the
      collected data, a linear mathematical model of sound attenuation on the way to
      the fetal ear was created. The results indicated a rise in the amount of sound
      attenuation for increasing frequencies. Analysis of slope coefficients for two
      muscle thicknesses revealed that there is no significant difference between
      attenuation by the thinner and the thicker tissue. Finally, the model was
      verified with data obtained during experiments on animals. The proposed model of
      the sound transmission allowed assessment of the attenuation by a soft tissue. It
      reveals changes in the sound reaching fetal ears, which can make acoustic
      stimulation different than what is heard in postnatal life. The model can be used
      to simulate the distortion of any sound which is proposed to prenatal stimulation
      and to assess its quality.

PMID- 29198466
TI  - Exertional myalgia, contractures and annular erythema in a patient with muscle
      lactate dehydrogenase (LDH) deficiency.

PMID- 29198467
TI  - Using CRISPR to inactivate endogenous retroviruses in pigs: an important step
      toward safe xenotransplantation?
AB  - Xenotransplantation could theoretically provide an unlimited supply of organs for
      patients living with end-stage kidney disease and other end-stage organ failure,
      but severe rejection and concerns about possible transmission of zoonotic
      infections remain important obstacles. In a recent study, investigators used
      CRISPR-cas9 to generate genetically modified pigs in which all endogenous
      retroviruses were inactivated. This approach may address one important barrier to
      the feasibility of clinical trials of xenotransplantation.

PMID- 29198468
TI  - High and low sodium intakes are associated with incident chronic kidney disease
      in patients with normal renal function and hypertension.
AB  - The association between salt intake and renal outcome in subjects with preserved
      kidney function remains unclear. Here we evaluated the effect of sodium intake on
      the development of chronic kidney disease (CKD) in a prospective cohort of people
      with normal renal function. Data were obtained from the Korean Genome and
      Epidemiology Study, a prospective community-based cohort study while sodium
      intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A
      total of 3,106 individuals with and 4,871 patients without hypertension were
      analyzed with a primary end point of CKD development [a composite of estimated
      glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of
      proteinuria during follow-up]. The median ages were 55 and 47 years, the
      proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73
      m2 in individuals with and without hypertension, respectively. During a median
      follow-up of 123 months in individuals with hypertension and 140 months in those
      without hypertension, CKD developed in 27.8% and 16.5%, respectively. After
      adjusting for confounders, multiple Cox models indicated that the risk of CKD
      development was significantly higher in people with hypertension who consumed
      less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between
      2.93-4.03 g/day sodium. However, there was no significant difference in the
      incident CKD risk among each quartile of people without hypertension. Thus, both
      high and low sodium intakes were associated with increased risk for CKD, but this
      relationship was only observed in people with hypertension.

PMID- 29198469
TI  - Novel Small-Molecule Inhibitors of Protein Kinase C Epsilon Reduce Ethanol
      Consumption in Mice.
AB  - BACKGROUND: Despite the high cost and widespread prevalence of alcohol use
      disorders, treatment options are limited, underscoring the need for new,
      effective medications. Previous results using protein kinase C epsilon
      (PKCepsilon) knockout mice, RNA interference against PKCepsilon, and peptide
      inhibitors of PKCepsilon predict that small-molecule inhibitors of PKCepsilon
      should reduce alcohol consumption in humans. METHODS: We designed a new class of
      PKCepsilon inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor
      Y-27632. In vitro kinase and binding assays were used to identify the most potent
      compounds. Their effects on ethanol-stimulated synaptic transmission; ethanol,
      sucrose, and quinine consumption; ethanol-induced loss of righting; and ethanol
      clearance were studied in mice. RESULTS: We identified two compounds that
      inhibited PKCepsilon with Ki <20 nM, showed selectivity for PKCepsilon over other
      kinases, crossed the blood-brain barrier, achieved effective concentrations in
      mouse brain, prevented ethanol-stimulated gamma-aminobutyric acid release in the
      central amygdala, and reduced ethanol consumption when administered
      intraperitoneally at 40 mg/kg in wild-type but not in Prkce-/- mice. One compound
      also reduced sucrose and saccharin consumption, while the other was selective for
      ethanol. Both transiently impaired locomotion through an off-target effect that
      did not interfere with their ability to reduce ethanol intake. One compound
      prolonged recovery from ethanol-induced loss of righting but this was also due to
      an off-target effect since it was present in Prkce-/- mice. Neither altered
      ethanol clearance. CONCLUSIONS: These results identify lead compounds for
      development of PKCepsilon inhibitors that reduce alcohol consumption.

PMID- 29198471
TI  - Sympatric Speciation in the Genomic Era.
AB  - Sympatric speciation has been of key interest to biologists investigating how
      natural and sexual selection drive speciation without the confounding variable of
      geographic isolation. The advent of the genomic era has provided a more nuanced
      and quantitative understanding of the different and often complex modes of
      speciation by which sympatric sister taxa arose, and a reassessment of some of
      the most compelling empirical case studies of sympatric speciation. However, I
      argue that genomic studies based on contemporary populations may never be able to
      provide unequivocal evidence of true primary sympatric speciation, and there is a
      need to incorporate palaeogenomic studies into this field. This inability to
      robustly distinguish cases of primary and secondary 'divergence with gene flow'
      may be inconsequential, as both are useful for understanding the role of large
      effect barrier loci in the progression from localised genic isolation to genome
      wide reproductive isolation. I argue that they can be of equivalent interest due
      to shared underlying mechanisms driving divergence and potentially leaving
      similar patterns of coalescence.

PMID- 29198472
TI  - Soft-tissue sarcoma risk in childhood cancer survivors.

PMID- 29198470
TI  - Parental Advisory: Maternal and Paternal Stress Can Impact Offspring
      Neurodevelopment.
AB  - Parental stress exposures are implicated in the risk for offspring
      neurodevelopmental and neuropsychiatric disorders, prompting critical examination
      of preconception and prenatal periods as vulnerable to environmental insults such
      as stress. Evidence from human studies and animal models demonstrates the
      influence that both maternal and paternal stress exposures have in changing the
      course of offspring brain development. Mechanistic examination of modes of
      intergenerational transmission of exposure during pregnancy has pointed to
      alterations in placental signaling, including changes in inflammatory, nutrient
      sensing, and epigenetic pathways. Transmission of preconception paternal stress
      exposure is associated with changes in epigenetic marks in sperm, with a primary
      focus on the reprogramming of DNA methylation, histone posttranslational
      modifications, and small noncoding RNAs. In this review, we discuss evidence
      supporting the important contribution of intergenerational parental stress in
      offspring neurodevelopment and disease risk, and the currently known epigenetic
      mechanisms underlying this transmission.

PMID- 29198473
TI  - Upfront resection of pancreatic intraductal neoplasms.

PMID- 29198474
TI  - Identifying precursor lesions of pancreatic cancer.

PMID- 29198476
TI  - Unilateral hand training on functional performance in patients with upper
      extremity trauma.
AB  - STUDY DESIGN: Case series. INTRODUCTION: Upper extremity (UE) trauma and
      subsequent immobilization affects functional performance. PURPOSE OF THE STUDY:
      Determine the usefulness and feasibility of unilateral hand training (UHT) on
      improving functional performance in patients with UE trauma. METHODS: Nine
      participants received UHT within 10 days of immobilization. Functional
      performance, dexterity, grip, and pinch strength were measured at initial and 4
      week visits. Qualitative interviews were coded to develop themes. RESULTS: All
      Jebsen-Taylor hand function test subtests improved from pretest to post-test.
      Disabilities of the Arm, Shoulder and Hand scores of all 9 participants improved.
      Functional performance was more impaired for participants with dominant UE
      injury. Four themes emerged: participants were forced to alter or avoid most
      daily activities, had an increased dependency on others, took longer to perform
      activities, and felt UHT decreased the impact of UE trauma on function.
      DISCUSSION: Functional performance was impaired for all participants.
      Participants believed that UHT was useful and contributed to improved function.
      CONCLUSION: This case series tracked a comprehensive intervention based on a
      holistic activities of daily living framework that considered the nuances of
      individual complexities of immobilization following hand trauma. Knowledge from
      this study supports an early intervention like UHT to educate clients on
      effective strategies to improve immediate activities of daily living functioning
      and potentially prevent longer term impairments.

PMID- 29198475
TI  - Learning to live with a hand nerve disorder: A constructed grounded theory.
AB  - STUDY DESIGN: Grounded theory. INTRODUCTION: The broader perspective of health
      offered by the World Health Organization's International Classification of
      Functioning, Disability and Health has had a significant bearing on how we view
      the measurement of health outcomes after surgical or therapy interventions for
      peripheral nerve disorders affecting the hand. The value of the patient's
      perspective is now recognized and outcomes which reflect this are being advocated
      in the clinical management and support of this population. PURPOSE OF THE STUDY:
      This qualitative study sought to explore the lived experience of a hand nerve
      disorder and in particular the impact on body structure/function, activities, and
      participation. METHODS: In depth, one-to-one interviews with 14 people with a
      range of hand nerve disorders were conducted. Constructivist grounded theory
      methods were used to collect and analyze the data. Patients were also given the
      option of taking photographs to visually represent what it is like to live with a
      nerve disorder, to bring with them for discussion during the interview. RESULTS:
      The impact of hand nerve disorders forms part of a wider narrative on adaptation.
      A process of "struggling" and then "overcoming" was experienced. This was
      followed by an interior aspect of adaptation described as "accepting." This gave
      rise to participants "transforming," being changed as a result of the journey
      that they had been on. CONCLUSIONS: This study provides an explanatory theory on
      the adaptive process following a hand nerve disorder which may inform future
      patient-therapist interactions.

PMID- 29198477
TI  - The assessment of psychological factors on upper extremity disability: A scoping
      review.
AB  - INTRODUCTION: The primary purpose of this scoping review was to describe the
      nature and extent of the published research that assesses the relationship
      between psychological features and patient-reported outcome following surgery or
      rehabilitation of upper extremity disease or injury. METHODS: Twenty-two included
      studies were examined for quantitative study design, outcome measure,
      inclusion/exclusion criteria, follow-up and recruitment strategy. Patient
      population and psychological assessment tools were examined for validity.
      RESULTS: Twenty-two studies met the inclusion criteria for this study. Only 7 of
      the 22 studies were longitudinal and the rest were cross sectional studies.
      Depression was the most common psychological status of interest and was included
      in 17 studies. Pain catastrophizing was the psychological status of interest in 5
      of the studies. Four studies considered anxiety, 3 considered pain anxiety, 3
      considered distress, 2 considered coping, 2 considered catastrophic thinking, and
      2 considered fear avoidance beliefs. DISCUSSION: The majority of studies in this
      review were cross-sectional studies. Cross-sectional studies may not provide
      conclusive information about cause-and-effect relationships. This review
      encourages clinicians to be mindful of the psychological implications found in
      rehabilitation of individuals with upper extremity disease or injury along with
      being cognizant of choosing appropriate measurement tools that best represent
      each patient's characteristics and diagnoses. CONCLUSIONS: The nature of the
      research addressing psychological factors affecting outcomes after hand injury
      focus on negative traits and have limited strength to suggest causation as most
      have used cross-sectional designs. Stronger longitudinal designs and
      consideration of positive traits are needed in future studies.

PMID- 29198478
TI  - The evaluation of a home-based program for hands in patients with systemic
      sclerosis.
AB  - STUDY DESIGN: This study used a quasi-experimental design where patients were
      evaluated before and after participation in the self-management program.
      INTRODUCTION: Hands are commonly affected in systemic sclerosis (SSc). Strategies
      to maintain or improve hand function are indicated upon diagnosis and throughout
      the course of the disease. PURPOSE OF THE STUDY: The purpose of this study was to
      develop and evaluate a home-based program for hands in patients with SSc.
      METHODS: A home-based self-management program that consisted of concise
      instructions about SSc and hand exercises was developed and evaluated in a group
      of patients with SSc during 8 weeks. Primary outcome measures were hand pain
      (Visual Analogue Scale) and hand function (Cochin Hand Function Scale). Secondary
      outcome measures were disability (Scleroderma Health Assessment Questionnaire),
      finger motion (delta finger-to-palm), grip strength, tip and key pinch strength,
      Raynaud phenomenon and digital ulcers impact, quality of life (Short Form Health
      Survey). For comparisons between different times analysis of variance for
      repeated measures was used. To calculate the effect size (ES), the Cohen's test
      was performed. To evaluate skin moisturizing and warming habits before and after
      intervention, the McNemar test was used. Statistical significance was set at P <=
      .05. RESULTS: Twenty-two SSc patients (19 women: 3 men; 16 limited scleroderma: 6
      diffuse scleroderma) completed the program. Significant improvements were noted
      for hand pain (3.97 vs 2.21, ES: 0.69), Cochin Hand Function Scale (19.24 vs
      12.48, ES: 0.48), Scleroderma Health Assessment Questionnaire (0.95 vs 0.48, ES:
      1.01), delta finger-to-palm (92.86 vs 106.33, ES: 0.40), grip strength (14.43 vs
      19, ES: 0.58), tip pinch strength (2.49 vs 4.18, ES: 1.15), key pinch strength
      (4.01 vs 5.22, ES: 0.76), Raynaud phenomenon impact (0.94 vs 0.47, ES: 0.75),
      Short Form Health Survey-role physical (47.38 vs 60.14, ES: 0.61), physical
      functioning (34.62 vs 61.9, ES: 0.18), social functioning (60.71 vs 75.6, ES:
      0.64), bodily pain (50.55 vs 63.38, ES: 0.58), vitality (45.95 vs 62, ES: 2.22),
      mental health (56.62 vs 72.38, ES: 0.84) moisturizing, and cold avoidance habits.
      Patients considered the program easy to follow with no adverse effects related to
      exercises. DISCUSSION: We developed a home based hand care program to be offered
      to SSc patients. Improvements in hand function, strength, disability, motion, and
      overall quality of life were independent of age, income, education level, disease
      duration, and skin score. Our findings support those of other studies that
      reported the benefits of hand exercises in SSc. Some study limitations include
      the lack of a control group, the small number of subjects and the short-time
      follow up. CONCLUSIONS: This home-based program for patients with SSc improved
      hand pain, function, mobility, and strength at the end of 8 weeks. Patient
      adherence and sustained efficacy is still to be determined.

PMID- 29198479
TI  - Multimodal custom orthosis to promote hook fist.

PMID- 29198480
TI  - Peptides isolated from animal venom as a platform for new therapeutics for the
      treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that deeply
      affects patients, their family and society. Although scientists have made intense
      efforts in seeking the cure for AD, no drug available today is able to stop AD
      progression. In this context, compounds isolated from animal venom are
      potentially successful drugs for neuroprotection, since they selectively bind to
      nervous system targets. In this review, we presented different studies using
      peptides isolated from animal venom for the treatment of AD. This is a growing
      field that will be very helpful in understanding and even curing
      neurodegenerative diseases, especially AD.

PMID- 29198481
TI  - Is it better to bend wires occlusally or apically during placement of arch bars
      for intermaxillary fixation?
AB  - We evaluated 78 patients who had intermaxillary fixation (IMF) of fractured
      mandibular condyles with arch bars and wires. Depending on whether the wires were
      bent apically or occlusally during placement of the arch bars, we randomly
      divided the patients into two groups (n=39 in each), then compared pain,
      satisfaction with oral hygiene, and complications between the groups at five to
      six weeks postoperatively when the arch bars were removed. Outcomes were
      significantly better in the occlusal group than in the apical group.

PMID- 29198482
TI  - Prognosis of oral cancer: a comparison of the staging systems given in the 7th
      and 8th editions of the American Joint Committee on Cancer Staging Manual.
AB  - The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual
      introduces "depth of invasion" and "extranodal extension" into the head and neck
      section, and our aim was to find out if these changes have an impact on
      prognosis. We evaluated 174 patients who had had oral squamous cell carcinomas
      (SCC) resected between 2003 and 2012. The clinical records were reviewed, the
      patients' tumours restaged according to the 8th edition of the AJCC, and we
      analysed five-year survival to verify whether different correlations were made
      between the T and N stages and disease-specific survival using the 7th and 8th
      editions. We excluded seven cases because information was incomplete, and the
      final sample was 167 patients. The five-year overall survival was 68% and the
      five-year disease-specific survival was 78%. The variable pT was upstaged in 51
      patients (31%), and no tumour was downstaged. When we used the 7th edition, the
      pT category did not correlate with survival (p=0.055), but when we used the 8th
      edition, there was a significant association between increased pT categories and
      disease-specific survival (p=0.01). In the pN category 23 cases were upstaged
      (14%) and this affected disease-specific survival using both the 7th and the 8th
      editions (p=0.001). When patients were restaged, there was an improvement in
      discrimination between T categories in relation to disease-specific survival, and
      confirmation of the prognostic impact of the variable pN. T stage and depth of
      invasion are complementary predictors of disease-specific survival, and their
      combination results in the new AJCC staging system giving a better prognosis.

PMID- 29198483
TI  - Making and working of a new electronic resource for patients, carers and
      professionals: maxfacts.uk.
AB  - Many maxillofacial patients have serious short, medium, or long-term problems, as
      well as having to make informed decisions about often life-changing
      interventions. Validated comprehensive information, at the right time and the
      right level for a diverse group of users (patients, carers, and professionals),
      is vital if patients are to make a serious contribution to their treatment. We
      describe the development of an online resource for this purpose. Maxfacts.uk aims
      to cover every aspect of oral and maxillofacial surgery and care, from neck
      dissection and ballistic wounds to physiotherapy and texture-modified foods. The
      principles of design, and the multilayered structure, interface, and functions of
      such a multiuser website are outlined, including accessibility and engagement.
      The maxfacts model and design could easily be adapted for other users with
      similar, complex, long-term needs.

PMID- 29198484
TI  - Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary
      complex: a retrospective study.
AB  - We designed a retrospective study to evaluate the efficacy of retroseptal
      transconjunctival approaches in the management of fractures of the
      zygomaticomaxillary complex (ZMC). The patients were from a single institution,
      and had had three-point fixation of fractures of the ZMC between 2008 and 2016. A
      total of 77 patients (56 men and 21 women with a mean (range) age of 28 (18-54)
      years), were divided into two groups. Group I (n=51) had had reduction and
      fixation of the infraorbital rim using a retroseptal transconjunctival approach.
      In group II (n=26) the same approach had been used with lateral canthotomy and
      inferior canthlolysis for both the infraorbital rim and the zygomaticofrontal
      region. We analysed the association of both approaches with the outcomes of
      reduction, fixation, and complications. Suboptimal results were found in 13
      patients in group I and one in group II (p=0.017). There were also three patients
      with trichiasis and two with entropion in group I, and one each of both
      complications in group II. There was only one patient with a malopposed lateral
      canthus in group II. All 26 patients in group II had no perceptible scar along
      the extended line of incision. The risk of a suboptimal outcome was reduced by
      20% (relative risk=0.8) in group II. The retroseptal transconjunctival approach
      with lateral canthotomy and inferior cantholysis is safe, aesthetic, and
      effective in the management of fractures of the ZMC.

PMID- 29198485
TI  - Nodular fasciitis of the temporomandibular joint: a case report.
AB  - Nodular fasciitis is a relatively rare benign lesion of the soft tissue, which
      often presents in the fascia or deep subcutaneous tissues. It most commonly
      presents in the upper extremities and trunk and the head and neck region,
      particularly in younger patients. Its pathogenesis is poorly understood and it is
      predominantly thought to be a reactive lesion, although some have suggested that
      it may be a benign neoplasm. Advances in molecular testing and imaging have
      greatly assisted diagnosis. We discuss the benefits of ubiquitin-specific
      protease 6 (USP6) gene rearrangement testing and magnetic resonance imaging (MRI)
      to aid this uncommon diagnosis.

PMID- 29198486
TI  - The Future of Exercise Tolerance Testing.

PMID- 29198487
TI  - Successful Endoscopic Resection of an Endobronchial Lipoma Using a Percutaneous
      Gastrostomy Snare Device.

PMID- 29198489
TI  - Opiate use disorders and overdose: Medical students' experiences, satisfaction
      with learning, and attitudes toward community naloxone provision.
AB  - INTRODUCTION: Opiate use disorder is a common condition in healthcare services in
      Ireland, where over 200 opiate overdose deaths occur annually. There is limited
      addiction medicine education at undergraduate level and medical graduates may not
      be adequately prepared to diagnose and manage opioid use disorders and emergency
      drug overdose presentations. Therefore, we examined final-year medical students'
      learning experiences and attitudes toward opioid use disorder, overdose and
      community naloxone provision as an emerging overdose treatment. METHODS: We
      administered an anonymous paper-based survey to 243 undergraduate medical
      students undertaking their final professional completion module prior to
      graduation from University College Dublin, Ireland. Results were compared with
      parallel surveys of General Practitioners (GPs) and GP trainees. RESULTS: A total
      of 197 (82.1%) completed the survey. Just under half were male, and most were
      aged under 25 (63.3%) and of Irish nationality (76.7%). The students felt
      moderately prepared to recognise opioid use disorder, but felt less prepared to
      manage other aspects of its care. Most had taken a history from a patient with an
      opioid use disorder (82.8%), and a third had witnessed at least one opioid
      overdose. Although 10.3% had seen naloxone administered, most had never
      administered naloxone themselves (98.5%). Half supported wider naloxone
      availability; this was lower than support rates among GPs (63.6%) and GP trainees
      (66.1%). CONCLUSIONS: Our findings suggest an unmet learning need in
      undergraduate training on opioid use disorder, with potential consequences for
      patient care.

PMID- 29198488
TI  - Measuring the heterophoria: Agreement between two methods in non-presbyopic and
      presbyopic patients.
AB  - PURPOSE: To establish whether the cover test and von Graefe methods are
      interchangeable in a non-presbyopic and presbyopic population. METHODS: We
      performed a prospective study on a sample of 127 non-presbyopic subjects between
      20 and 45 years old and 56 presbyopic between 40 and 78 years old. Distance and
      near vision phoria were measured using the von Graefe method (VG) and cover test
      (CT). We analyzed the significant differences between methods, their correlation
      and the agreement between them using the Bland and Altman method. RESULTS: For
      distance vision, heterophoria values for non-presbyopic subjects were -0.61+/
      1.86Delta with CT and -0.88+/-2.37Delta with VG, and for presbyopic subjects were
      -0.56+/-1.64Delta with CT and -0.85+/-1.94Delta with VG. For near vision, CT
      yielded -3.02+/-3.97Delta, while VG achieved -3.49+/-4.70Delta in non-presbyopic
      subjects. For presbyopic subjects these values were -6.05+/-4.38Delta with CT and
      -6.29+/-4.19Delta with VG, respectively. Statistically significant differences
      between the two methods were observed for all groups analyzed (p<0.05), except
      for near vision in presbyopic subjects (p>0.05). Coefficient of agreement for non
      presbyopic was +/-2.97Delta for distance vision and +/-6.74Delta at near. For
      presbyopic patients, this coefficient was +/-1.59Delta for distance and +/
      1.86Delta for near vision. CONCLUSION: Cover test and von Graefe methods have a
      high level of agreement for both distance and near vision when considering
      presbyopic subjects. For non-presbyopic patients, the level of agreement is very
      low. Both methods for measuring heterophoria can only be considered
      interchangeable for presbyopic patients. For clinical purposes, this implies that
      any method can be used for measuring heterophoria in presbyopic patients.

PMID- 29198490
TI  - Overdose and adverse drug event experiences among adult patients in the emergency
      department.
AB  - INTRODUCTION: Overdose is a leading cause of injury and death in the United
      States. Emergency Department (ED) patients have an elevated prevalence of
      substance use. This study describes overdose/adverse drug event experiences among
      adult ED patients to inform strategies to address overdose risk. METHODS:
      Patients seeking care at a large ED in the city of Flint, Michigan participated
      in a computerized self-assessment during 2011-2013 (n=4571). Overdose was
      assessed with a broad definition and included occurrences that could be
      considered adverse drug events. Among those with this type of experience,
      additional items assessed symptoms, outcomes, and intent. RESULTS: 12% reported
      an overdose history. Of participants' most serious overdoses, 74% were without
      clear intent for self-harm, although this was true of only 61% of overdoses
      involving opiates or sedatives, and 52% had symptoms present that indicated that
      it was life-threatening. Binge drinking on a monthly basis (ORs=1.4) was
      associated with a medically serious overdose compared to never having an
      overdose. Compared to no drug use in the last year, use of one drug was
      associated with an OR of 1.8, two drugs was associated with an OR of 5.8, three
      drugs was associated with an OR of 8.4, and four or more drugs was associated
      with an OR of 25.1 of having had a medically serious overdose (all p<0.05).
      CONCLUSIONS: Most overdose experiences among ED patients were without clear
      intent of self-harm. The ED may be an appropriate setting for efforts to reduce
      overdose risk, especially among polysubstance users.

PMID- 29198491
TI  - Preliminary algorithm for differential diagnosis between spinal meningioma and
      schwannoma using plain magnetic resonance imaging.
AB  - BACKGROUND: Preoperative differential diagnosis between spinal meningioma and
      schwannoma is critical due to the characteristic differences of the surgical
      treatments. Thus, we aimed to develop an algorithm for the differential diagnosis
      of these two lesions based on plain MRI findings. METHODS: We retrospectively
      reviewed plain MR images from patients who had undergone surgical treatment for
      meningiomas and schwannomas in our hospital between 2002 and 2016. Seven findings
      characteristic of meningioma or schwannoma were considered: (a) low or equal
      signal intensity on T2-weighted images, (b) obtuse angle from the dura mater, (c)
      anterior location in the spinal canal, (d) cystic degeneration, (e) lumbar
      occurrence, (f) oval or round shape, and (g) dumbbell type. We calculated the
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy of each MRI finding, following which the algorithm was
      developed using decision tree analysis. Finally, we examined the usefulness of
      the algorithm for differential diagnosis between the two lesions. RESULTS: Twenty
      four patients with meningiomas and 56 with schwannomas were enrolled. The
      sensitivity, specificity, PPV, NPV, and accuracy of each finding were as follows:
      (a) [58%, 100%, 100%, 85%, 88%], (b) [67%, 89%, 73%, 86%, 83%], (c) [29%, 88%,
      50%, 74%, 70%], (d) [30%, 96%, 94%, 37%, 50%], (e) [43%, 96%, 96%, 42%, 59%], (f)
      [33%, 88%, 73%, 57%, 60%], and (g) [25%, 96%, 93%, 35%, 46%]. Significant
      differences were observed with regard to (a), (b), (d), (e), and (g). The
      algorithm was developed using these five findings, all of which exhibited high
      specificity and reliability. Accuracy of the algorithm was 91.3%. CONCLUSIONS:
      Our results indicated that plain MRI findings can be used to differentiate
      between spinal meningiomas and schwannomas. Furthermore, our novel algorithm
      exhibited high accuracy, suggesting that this algorithm may aid in the
      differential diagnosis of these two lesions.

PMID- 29198492
TI  - Adequate lymph node evaluation in the elderly is associated with improved
      survival in patients with stage I-III colon cancer: A validation study using the
      National Cancer Data Base.
AB  - BACKGROUND: Lymph node involvement (LNI) is an important prognostic factor in
      colon cancer. But, variations in LNI among different age groups are less known.
      Adequate lymph node evaluation (LNE) requires assessment of >=12 nodes. In our
      previous study, using Surveillance, Epidemiology and End Results (SEER) data, we
      demonstrated that older patients are less likely to have LNI (Khan et al. 2014).
      Our current study validates those findings using National Cancer Data Base
      (NCDB). METHODS: NCDB was queried for patients diagnosed with stages I-III colon
      adenocarcinoma from 2004 to 2008 who underwent surgical resections. Pearson Chi
      square test and Cox proportional hazards regression model were utilized for
      statistical analysis. RESULTS: A cohort of 97,831 patients was identified for
      analysis. Among patients belonging to 18-64, 65-74 and >75 years age groups,
      frequency of adequate LNE was 73.6%, 69% and 67.4% respectively, with
      pathologically confirmed LNI rates being 44.7%, 37.8% and 29.3% respectively (p <
      0.0001). Adequate LNE was associated with improved 5-year overall survival (OS)
      regardless of age, gender, race, comorbidity index, insurance, income, year of
      diagnosis, pathologic tumor status, stage, grade, type of colectomy, adjuvant
      chemotherapy or academic level of facility. Rates of adequate LNE increased from
      2004 to 2008, with a corresponding increase in survival outcomes (p < 0.0001).
      CONCLUSION: Adequate LNE is very crucial for appropriate staging of colon cancer,
      and carries a high prognostic value. This study validates our previous findings
      of lower rates of LNI in elderly and reiterates the importance of adequate LNE,
      which is associated with improved survival. Also identified were increasing rates
      of adequate LNE over the years, with corresponding improvement in OS.

PMID- 29198493
TI  - Impact of associating liver partition and portal vein occlusion for staged
      hepatectomy on tumor growth in a mouse model of liver metastasis.
AB  - BACKGROUND: The impact of associating liver partition and portal vein occlusion
      for staged hepatectomy (ALPPS) on tumor growth activity was investigated.
      METHODS: A BALB/c mouse model (male, 8-10 weeks old) of liver metastasis labeled
      by red fluorescent protein was established. Changes in future liver remnant (FLR)
      volumes, tumor growth activity, and levels of cytokines and growth factors in
      liver tissues during the treatment period were compared among the models
      involving ALPPS, portal vein ligation (PVL), or sham operation. RESULTS: The
      ratio of the FLR volume to body weight at 24 h after the procedure was greater
      for ALPPS (4.45 +/- 0.12 * 10-2) than for PVL (3.79 +/- 0.12 * 10-2; P = 0.003)
      and sham operation (3.18 +/- 0.16 * 10-2; P < 0.001). No differences in tumor
      progression in the FLR were observed at any time point after the procedures.
      Within the deportalized liver (DL), although tumor progression was observed
      during a later period after ALPPS (9 days postoperative) and PVL (12 days
      postoperative), no acceleration of tumor growth after ALPPS was observed in an
      early period similar to PVL. CONCLUSION: ALPPS induces a rapid increase in FLR
      volume and avoids remnant tumor progression during the early postoperative
      period.

PMID- 29198494
TI  - Distribution of metastases in mesorectum is unpredictable: Metastases do not
      respect tumor localization even in small non-circumferential rectal cancers.
AB  - INTRODUCTION: Low anterior resection with total mesorectal excision (TME) is the
      gold standard for surgical treatment of rectal carcinoma. The radicality of this
      procedure is negatively counterbalanced by morbidity, lethality, and numerous
      other complications. Local excision would appear to be an attractive alternative,
      but its radicality is disputable due to risk of undetected metastasis to the
      mesorectum. The study aimed to determine the location of mesorectal metastases
      with respect to circumferentially - located tumors in patients with tumors
      involving less than one-third of the rectal circumference. MATERIALS AND METHODS:
      Resected specimens from patients with tumors smaller than one-third of the
      circumference were divided into: Sector A - tumorous, and Sector B - nontumorous.
      Group A was created by the pathologist cutting part of the rectal wall with the
      adjacent mesorectum, as though imitating a full-thickness excision. RESULTS: The
      study comprised 35 patients with a mean age of 66 years, of which 23 were men
      (65.7%) and 12 were women (34.2%). Tumors were predominantly (y)pT1-T2; a total
      of 799 lymph nodes and 5 tumor satellites were examined. Six patients (17.1%)
      were identified as stage (y)pN+. A total of 3 positive findings (lymph node
      metastasis or satellites) were detected in 3 patients (8.5%) in tumorous Sector
      A; and 8 positive findings were detected in 4 patients (11.4%) in non-tumorous
      Sector B. CONCLUSION: Rectal carcinoma involving one-third of the rectal
      circumference metastasizes discontinuously, and spreads into parts of the
      mesorectum beyond the tumor area.

PMID- 29198496
TI  - Corrigendum to "Spinocerebellar ataxia: miRNAs expose biological pathways
      underlying pervasive Purkinje cell degeneration" [Neurobiol. Dis. 2017 Dec 108
      148-158].

PMID- 29198497
TI  - Genes and pathways in optic fissure closure.
AB  - Embryonic development of the vertebrate eye begins with the formation of an optic
      vesicle which folds inwards to form a double-layered optic cup with a fissure on
      the ventral surface, known as the optic fissure. Closure of the optic fissure is
      essential for subsequent growth and development of the eye. A defect in this
      process can leave a gap in the iris, retina or optic nerve, known as a coloboma,
      which can lead to severe visual impairment. This review brings together current
      information about genes and pathways regulating fissure closure from human
      coloboma patients and animal models. It focuses especially on current
      understanding of the morphological changes and processes of epithelial
      remodelling occurring at the fissure margins.

PMID- 29198495
TI  - Prognostic value of peritoneal cancer index in primary advanced ovarian cancer.
AB  - BACKGROUND: Effective tumor debulking is a major factor associated with a
      favorable prognosis in patients with advanced ovarian cancer (AOC). However, FIGO
      staging fails to take full account of the extent of the disease in the
      peritoneum, making it difficult to plan appropriate surgical treatment. In
      contrast, the peritoneal cancer index (PCI) can provide more detailed information
      about peritoneal spread. METHOD: We evaluated the prognostic value of PCI and its
      association with clinicopathological features in patients with AOC. Data for 80
      patients with AOC who underwent primary debulking surgery were analyzed
      retrospectively. PCI scores of 0-39 were calculated based on the sizes of lesions
      in 13 abdominopelvic regions, and patients were classified into three categories
      with scores of 1-10, 11-20, and >20, respectively. Clinicopathological features,
      including the presence of residual tumor after surgery and the incidence of
      postoperative complications, were assessed in relation to PCI score. RESULTS: PCI
      was significantly associated with suboptimal surgery and postoperative
      complications, as well as with preoperative CA125, ascites, prolonged surgery,
      FIGO stage, positive aortic lymph nodes, prolonged hospitalization, and number of
      visceral resections. Overall and disease-free survival was also associated with
      PCI, with an optimal cut-off value of 15. Multivariate analysis identified age,
      residual tumor, and PCI as independent prognostic factors for survival. A PCI >10
      is positively associated with a poor prognosis in patients with AOC. CONCLUSION:
      Given the importance of effective tumor debulking, PCI may provide important
      information for surgical planning in patients with AOC.

PMID- 29198498
TI  - Pneumocystis jirovecii pneumonia in patients treated with rituximab for systemic
      diseases: Report of 11 cases and review of the literature.

PMID- 29198500
TI  - Subclinical synovitis and tenosynovitis by ultrasonography (US) 7 score in
      patients with rheumatoid arthritis treated with synthetic drugs, in clinical
      remission by DAS28.
AB  - OBJECTIVE: To identify synovitis and tenosynovitis active by using the Ultrasound
      7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical
      remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs).
      METHODS: This is a multicentric, cross-sectional, observational study including
      94 RA patients >18 years old who were in remission as defined by the 28-joints
      disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6
      months. Patients with a previous or current history of biologic DMARD treatment
      were not included in the study. Demographic and clinical data were collected by
      the local rheumatologist; the US evaluation was performed by a calibrated
      rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD)
      using the 7-joint scale. Intra and inter-reader exercises of images between 2
      ultrasonographers were realized. RESULTS: Patients' mean age was 49.1+/-13.7
      years; 83% were women. The mean disease duration was 8+/-7 years and remission
      lasted for 27.5+/-31.8 months. The mean DAS28 score was 1.9+/-0.66. Grayscale
      synovitis was present in 94% of cases; it was mild in 87.5% and moderate in
      12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal,
      metacarpophalangeal, and carpal joints of the dominant hand were the joints more
      frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9
      patients (9.6%). The intra and inter-reading kappa value were 0.77, p<0.003 (CI
      95%, 0.34-0.81) and 0.81, p<0.0001 (CI 95%, 0.27-0.83) respectively. CONCLUSIONS:
      Low percentage of synovitis and tenosynovitis active were founded according to PD
      US by 7 score in RA patients under synthetic DMARDs during long remission. This
      score has benefit because evaluate tenosynovitis, another element of subclinical
      disease activity.

PMID- 29198499
TI  - Markers of impaired motor and cognitive volition in Parkinson's disease:
      Correlates of dopamine dysregulation syndrome, impulse control disorder, and
      dyskinesias.
AB  - INTRODUCTION: Dopaminergic therapy in Parkinson's disease (PD) can be associated
      with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects.
      Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse
      control disorder (ICD), which are separate but related behavioral/psychiatric
      complications of treatment in PD. Dysregulation of volition characterizes both
      dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates
      in a large PD cohort. METHODS: We analyzed cross-sectional data from 654
      participants collected through the NINDS Parkinson's Disease Biomarkers Program.
      DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders
      Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated
      variables were selected from PD-validated or PD-specific scales of
      neuropsychiatric or motoric status. Multivariable models with DDS/ICD or
      dyskinesia presence outcomes were produced with backward stepwise regression to
      identify factors independently associated with DDS/ICD and/or dyskinesias.
      RESULTS: Fifty-three (8.1%) participants endorsed DDS and/or ICD symptoms and 150
      (22.9%) were dyskinetic. In multivariable analysis, psychosis was independently
      associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001).
      Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also
      associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and
      high akinesia-rigidity score (p < 0.001) were associated with dyskinesias.
      CONCLUSIONS: Our findings suggest that psychosis may be an important marker of
      impaired volition across motor and cognitive domains. Unpredictable motor
      fluctuations, psychosis, and depression may together comprise a phenotypic
      profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD
      patients should be closely monitored for psychotic symptoms and treated
      appropriately.

PMID- 29198501
TI  - Social resources and Arab women's perinatal mental health: A systematic review.
AB  - BACKGROUND: Women's mental health in the perinatal period is understudied
      worldwide and in Arab countries especially. AIM: This systematic review explores
      evidence of the association between women's social resources for empowerment in
      the Arab World and their mental health in the prenatal and postnatal (<=1year
      postpartum) periods. METHODS: Guided by Kabeer's framework of empowerment, the
      authors applied a search string in PubMed and Web of Science databases to
      identify studies in countries of the Arab League (hereafter the Arab World) that
      address mental health and social resources for women's empowerment in the
      perinatal period. FINDINGS: Of 1865 electronically retrieved articles, 23 met the
      inclusion criteria. Overall, the majority of studies found a positive association
      between social resources for empowerment and perinatal mental health. Seven
      studies explored the relationship between familial or general social support and
      prenatal mental health in Arab women, and found a significant positive
      association. Sixteen of the 18 studies of women in the postnatal period found
      that enabling familial, extra-familial, and/or general social support was
      positively associated with mental health. CONCLUSION: This review demonstrates an
      association between social resources and perinatal mental health, but there is a
      dearth of research in this area. We call for additional research on Arab women in
      the perinatal period using context-specific but standardized tools to assess
      social resources and mental health. Evidence on positive mental health,
      resilience, and the influence of social resources can guide the improvement of
      prenatal and postpartum care services.

PMID- 29198502
TI  - Pregnant women's choice of birthing hospital: A qualitative study on individuals'
      preferences.
AB  - OBJECTIVE: To investigate pregnant women's decision making in relation to their
      choice of birthing hospital and, in particular, their priorities regarding
      hospital characteristics. METHODS: The focus of this study was the choice of
      birthing hospital among pregnant women. A qualitative interview design was used
      and women were recruited during their first pregnancy-related visit to a general
      practitioner. The interviews were conducted using a semi-structured interview
      guide, and a thematic analysis of the data was carried out. RESULTS: Women made
      their hospital choice decision independently and they relied extensively on their
      own or peers' experiences. Travel distance played a role, but some women were
      willing to incur longer travel times to give birth at a specialized hospital in
      order to try to reduce the risks (in case of unexpected events). The women
      associated the presence of specialized services and staff that were more
      qualified and experienced with increased safety. Other priorities included
      continuity of care (i.e., being seen by the same midwife) as well as service
      availability, which in this case referred to the possibility of a water birth and
      postnatal hoteling services. CONCLUSIONS: The choice of hospital provider appears
      to be strongly influenced by experience, whether personal experience or the
      experience of peers. However, there appears to be room for more information to be
      provided on safety and service attributes as an instrument for making an informed
      decision.

PMID- 29198503
TI  - EEG background activity and extreme delta brush in children with anti-NMDAR
      encephalitis.

PMID- 29198505
TI  - Revisiting Ray Moynihan.

PMID- 29198504
TI  - Female Sexual Dysfunction-Medical and Psychological Treatments, Committee 14.
AB  - INTRODUCTION: Since the millennium we have witnessed significant strides in the
      science and treatment of female sexual dysfunction (FSD). This forward progress
      has included (i) the development of new theoretical models to describe healthy
      and dysfunctional sexual responses in women; (ii) alternative classification
      strategies of female sexual disorders; (iii) major advances in brain, hormonal,
      psychological, and interpersonal research focusing on etiologic factors and
      treatment approaches; (iv) strong and effective public advocacy for FSD; and (v)
      greater educational awareness of the impact of FSD on the woman and her partner.
      AIMS: To review the literature and describe the best practices for assessing and
      treating women with hypoactive sexual desire disorder, female sexual arousal
      disorder, and female orgasmic disorders. METHODS: The committee undertook a
      comprehensive review of the literature and discussion among themselves to
      determine the best assessment and treatment methods. RESULTS: Using a
      biopsychosocial lens, the committee presents recommendations (with levels of
      evidence) for assessment and treatment of hypoactive sexual desire disorder,
      female sexual arousal disorder, and female orgasmic disorders. CONCLUSION: The
      numerous significant strides in FSD that have occurred since the previous
      International Consultation of Sexual Medicine publications are reviewed in this
      article. Although evidence supports an integrated biopsychosocial approach to
      assessment and treatment of these disorders, the biological and psychological
      factors are artificially separated for review purposes. We recognize that best
      outcomes are achieved when all relevant factors are identified and addressed by
      the clinician and patient working together in concert (the sum is greater than
      the whole of its parts). Kingsberg SA, Althof S, Simon JA, et al. Female Sexual
      Dysfunction-Medical and Psychological Treatments, Committee 14. J Sex Med
      2017;14:1463-1491.

PMID- 29198506
TI  - The Need of Patient Involvement in Transgender Health Care Research.

PMID- 29198507
TI  - British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency,
      With Statements for UK Practice.
AB  - BACKGROUND: Testosterone deficiency (TD) is an increasingly common problem with
      significant health implications, but its diagnosis and management can be
      challenging. AIM: To review the available literature on TD and provide evidence
      based statements for UK clinical practice. METHODS: Evidence was derived from
      Medline, EMBASE, and Cochrane searches on hypogonadism, testosterone (T) therapy,
      and cardiovascular safety from May 2005 to May 2015. Further searches continued
      until May 2017. OUTCOMES: To provide a guideline on diagnosing and managing TD,
      with levels of evidence and grades of recommendation, based on a critical review
      of the literature and consensus of the British Society of Sexual Medicine panel.
      RESULTS: 25 statements are provided, relating to 5 key areas: screening,
      diagnosis, initiating T therapy, benefits and risks of T therapy, and follow-up.
      7 statements are supported by level 1, 8 by level 2, 5 by level 3, and 5 by level
      4 evidence. CLINICAL IMPLICATIONS: To help guide UK practitioners on effectively
      diagnosing and managing primary and age-related TD. STRENGTHS AND LIMITATIONS: A
      large amount of literature was carefully sourced and reviewed, presenting the
      best evidence available at the time. However, some statements provided are based
      on poor-quality evidence. This is a rapidly evolving area of research and
      recommendations are subject to change. Guidelines can never replace clinical
      expertise when making treatment decisions for individual patients, but rather
      help to focus decisions and take personal values and preferences and individual
      circumstances into account. Many issues remain controversial, but in the
      meantime, clinicians need to manage patient needs and clinical expectations armed
      with the best clinical evidence and the multidisciplinary expert opinion
      available. CONCLUSION: Improving the diagnosis and management of TD in adult men
      should provide somatic, sexual, and psychological benefits and subsequent
      improvements in quality of life. Hackett G, Kirby M, Edwards D, et al. British
      Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With
      Statements for UK Practice. J Sex Med 2017;14:1504-1523.

PMID- 29198508
TI  - The "G-Spot" Is Not a Structure Evident on Macroscopic Anatomic Dissection of the
      Vaginal Wall.
AB  - BACKGROUND: Controversy exists in the literature regarding the presence or
      absence of an anatomic "G-spot." However, few studies have examined the detailed
      topographic or histologic anatomy of the putative G-spot location. AIM: To
      determine the anatomy of the anterior vaginal wall and present detailed,
      systematic, accessible findings from female cadaveric dissections to provide
      anatomic clarity with respect to this location. METHODS: Systematic anatomic
      dissections were performed on 13 female cadavers (32-97 years old, 8 fixed and 5
      fresh) to characterize the gross anatomy of the anterior vaginal wall. Digital
      photography was used to document dissections. Dissection preserved the anterior
      vaginal wall, urethra, and clitoris. In 9 cadavers, the vaginal epithelial layer
      was reflected to expose the underlying urethral wall and associated tissues. In 4
      cadavers, the vaginal wall was left intact before preservation. Once
      photographed, 8 specimens were transversely sectioned for macroscopic inspection
      and histologic examination. OUTCOMES: The presence or absence of a macroscopic
      anatomic structure at detailed cadaveric pelvis dissection that corresponds to
      the previously described G-spot and gross anatomic description of the anterior
      vaginal wall. RESULTS: Deep to the lining epithelium of the anterior vaginal wall
      is the urethra. There is no macroscopic structure other than the urethra and
      vaginal wall lining in the location of the putative G-spot. Specifically, there
      is no apparent erectile or "spongy" tissue in the anterior vaginal wall, except
      where the urethra abuts the clitoris distally. CLINICAL IMPLICATIONS: The absence
      of an anatomic structure corresponding to the putative G-spot helps clarify the
      controversy on this subject. STRENGTHS AND LIMITATIONS: Limitations to this study
      include limited access to specimens immediately after death and potential for
      observational bias. In addition, age, medical history, and cause of death are not
      publishable for privacy reasons. However, it is one of the most thorough and
      complete anatomic evaluations documenting the anatomic detail of the anterior
      vaginal wall. CONCLUSION: The G-spot, in its current description, is not
      identified as a discrete anatomic entity at macroscopic dissection of the urethra
      or vaginal wall. Further insights could be provided by histologic study. Hoag N,
      Keast JR, O'Connell HE. The "G-Spot" Is Not a Structure Evident on Macroscopic
      Anatomic Dissection of the Vaginal Wall. J Sex Med 2017;14:1524-1532.

PMID- 29198509
TI  - Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of
      Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.
AB  - BACKGROUND: Testosterone is believed to mediate the penile erectile response by
      producing adequate nitric oxide; therefore, testosterone deficiency results in
      erectile dysfunction through decreased nitric oxide bioavailability. However, the
      mechanisms underlying endothelial dysfunction in testosterone deficiency remain
      unclear. AIM: To investigate the mechanism of endothelial dysfunction in a rat
      model of testosterone deficiency. METHODS: Rats were distributed into 3 groups:
      castrated (Cast), castrated and supplemented with testosterone (Cast + T), and
      sham (Sham). In the Cast + T group, castrated rats were treated daily with
      subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats
      received only the vehicle. OUTCOMES: Erectile function using intracavernosal
      pressure and mean arterial pressure measurements after electrical stimulation of
      the cavernous nerve, endothelial function using isometric tension, asymmetric
      dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and
      tandem mass spectrometry, and inflammatory biomarker expression were performed 4
      weeks after the operation. RESULTS: In the Cast group, the ratio of
      intracavernosal pressure to mean arterial pressure significantly decreased,
      acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and
      inflammation biomarker levels were significantly increased (P < .01).
      Testosterone injection significantly improved each of these parameters (P < .01).
      CLINICAL TRANSLATION: The present results provide scientific evidence of the
      effect of testosterone deficiency on erectile function and the effect of
      testosterone replacement therapy. STRENGTHS AND LIMITATIONS: This study provides
      evidence of the influence of testosterone deficiency on endothelial function by
      investigating ADMA and oxidative stress. A major limitation of this study is the
      lack of a direct link of increased ADMA by oxidative stress to inflammation.
      CONCLUSION: Testosterone deficiency increased not only ADMA levels but also
      oxidative stress and inflammation in castrated rats, which can cause damage to
      the corpus cavernosum, resulting in erectile dysfunction. Kataoka T, Hotta Y,
      Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via
      Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.
      J Sex Med 2017;14:1540-1548.

PMID- 29198510
TI  - Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From
      Sexual Symptom Impairment? Findings of a Cross-Sectional Study.
AB  - BACKGROUND: Although erectile dysfunction (ED) has been associated with low
      circulating total testosterone (TT) levels, the utility of free testosterone (FT)
      over TT is debatable. AIM: To assess the relative impact of low TT and low
      calculated FT (cFT) on androgen-related sexual symptoms in men with ED. METHODS:
      Data from 485 men were analyzed. Comorbidities were scored with the Charlson
      Comorbidity Index (CCI). Patients completed the International Index of Erectile
      Function (IIEF) and the Beck Inventory for Depression (BDI). Descriptive
      statistics tested differences between patients with normal TT levels (>3 ng/mL)
      and normal cFT levels (>65 pg/mL; group 1) and men with normal TT and low cFT
      (group 2), low TT and normal cFT (group 3), and low TT and low cFT (group 4).
      Linear regression models tested the association between clinical predictors and
      sexual function impairment. OUTCOMES: We assessed the impact of different
      hormonal categories on androgen-related symptoms and the clinical utility of
      measuring cFT in men with ED. RESULTS: Groups 1, 2, 3, and 4 were composed of 338
      (69.6%), 44 (9.1%), 34 (7.0%), and 69 (14.3%) patients, respectively. Compared
      with group 1, patients in group 2 were older (P < .001), had a higher body mass
      index (P < .01), and had a larger proportion with CCI scores of at least 1 (P =
      .006). Likewise, group 2 presented lower scores for the IIEF erectile function (P
      = .07), sexual desire (P = .04), and orgasmic function (P = .007) domains and
      lower BDI scores (P = .02) than group 1. Similar findings were found for group 4
      vs 1. Conversely, patients in group 3 had similar scores on the questionnaires to
      those in group 1. Low cFT and normal or low TT achieved independent predictor
      status for pathologic IIEF domains and BDI scores after accounting for age, CCI,
      and body mass index. Conversely, low TT and normal cFT status was not associated
      with pathologic scores on the questionnaires. CLINICAL IMPLICATIONS: The
      inclusion of cFT in the first-line assessment of hypogonadal symptoms in men with
      ED has major clinical utility. STRENGTHS AND LIMITATIONS: This is the first study
      evaluating the concomitant impact of TT and cFT on men with ED using well
      validated instruments to assess patients' sexuality and depressive symptoms.
      Limitations are the retrospective nature of the study and lack of physical
      function data and bone ultrasound measurements. CONCLUSIONS: Although normal cFT
      was not associated with signs and symptoms suggestive of testosterone deficiency,
      even when concomitant with low TT or low cFT irrespective of TT values, it was
      indicative of poorer clinical profiles and impaired sexual and depressive
      parameters compared with normal TT and normal cFT in a cohort of patients with
      ED. Boeri L, Capogrosso P, Ventimiglia E, et al. Does Calculated Free
      Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom
      Impairment? Findings of a Cross-Sectional Study. J Sex Med 2017;14:1549-1557.

PMID- 29198511
TI  - Preliminary Evidence for an Association Between Variants of the Catechol-O
      Methyltransferase (COMT) Gene and Premature Ejaculation.
AB  - BACKGROUND: Studies have suggested that dopamine plays a role in the
      neurobiological mechanism that triggers ejaculation, leading scientists to
      hypothesize that dopamine-related genetic polymorphisms could contribute to
      symptoms of premature ejaculation (PE). AIM: To investigate associations between
      dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in
      the catabolism of dopamine) gene-linked polymorphisms and PE. METHODS: PE status
      in patient groups was determined by clinical diagnosis performed by a physician
      specializing in sexual medicine. Self-reported PE symptoms from a validated
      questionnaire also were reported. Saliva samples were collected from 149 patients
      with PE and 1,022 controls from a population-based sample. In total, we tested
      associations between PE and 11 single-nucleotide polymorphisms in the dopamine
      receptor D1, D2, and D3 genes and in the COMT gene. OUTCOMES: We found no
      associations between dopamine receptor gene polymorphisms and PE, but 2 COMT
      linked loci (rs4680 and rs4818) had significant associations after correction for
      multiple testing. RESULTS: 1 COMT gene-linked locus that was associated with PE
      symptoms in the present study, rs4680, is a well-documented functional
      polymorphism that causes a valine-to-methionine substitution. The other
      polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus,
      indicating that they capture the same effect. Surprisingly, the rs4680 variant
      that was statistically significantly more prevalent in the PE group (ie, the
      valine-encoding allele) has been associated with higher enzymatic activity and
      therefore lower synaptic dopamine levels. CLINICAL TRANSLATION: Drugs targeting
      the dopaminergic system could affect PE symptoms. STRENGTHS AND LIMITATIONS: No
      replication sample was available for the present study; thus, our findings should
      be interpreted with caution. Moreover, a limitation of our study is the small
      sample in the context of genetic association studies (although it should be
      mentioned that genetically informative samples with phenotypic information about
      PE symptoms are scarce, and most previous genetic association studies of PE have
      used samples of similar or smaller size). However, our results are plausible: we
      report an association between one of the most extensively studied and understood
      genetic polymorphisms in psychiatric research and PE, and our results are in line
      with the long-standing hypothesis that dopamine influences human ejaculatory
      function. CONCLUSIONS: We report an association between 2 COMT gene-linked loci
      and PE symptoms, but our results should be treated with caution until
      independently replicated. Jern P, Johansson A, Strohmaier J, et al. Preliminary
      Evidence for an Association Between Variants of the Catechol-O-Methyltransferase
      (COMT) Gene and Premature Ejaculation. J Sex Med 2017;14:1558-1565.

PMID- 29198512
TI  - Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder
      and Treatment Options.
AB  - BACKGROUND: The neurobiology of sexual response is driven in part by dopamine and
      serotonin-the former modulating excitatory pathways and the latter regulating
      inhibitory pathways. Neurobiological underpinnings of hypoactive sexual desire
      disorder (HSDD) are seemingly related to overactive serotonin activity that
      results in underactive dopamine activity. As such, pharmacologic agents that
      decrease serotonin, increase dopamine, or some combination thereof, have
      therapeutic potential for HSDD. AIM: To review the role of serotonin in female
      sexual function and the effects of pharmacologic interventions that target the
      serotonin system in the treatment of HSDD. METHODS: Searches of the Medline
      database for articles on serotonin and female sexual function. OUTCOMES: Relevant
      articles from the peer-reviewed literature were included. RESULTS: Female sexual
      response is regulated not only by the sex hormones but also by several
      neurotransmitters. It is postulated that dopamine, norepinephrine, oxytocin, and
      melanocortins serve as key neuromodulators for the excitatory pathways, whereas
      serotonin, opioids, and endocannabinoids serve as key neuromodulators for the
      inhibitory pathways. Serotonin appears to be a key inhibitory modulator of sexual
      desire, because it decreases the ability of excitatory systems to be activated by
      sexual cues. Centrally acting drugs that modulate the excitatory and inhibitory
      pathways involved in sexual desire (eg, bremelanotide, bupropion, buspirone,
      flibanserin) have been investigated as treatment options for HSDD. However, only
      flibanserin, a multifunctional serotonin agonist and antagonist (5
      hydroxytryptamine [5-HT]1A receptor agonist and 5-HT2A receptor antagonist), is
      currently approved for the treatment of HSDD. CLINICAL IMPLICATIONS: The central
      serotonin system is 1 biochemical target for medications intended to treat HSDD.
      STRENGTHS AND LIMITATIONS: This narrative review integrates findings from
      preclinical studies and clinical trials to elucidate neurobiological
      underpinnings of HSDD but is limited to 1 neurotransmitter system (serotonin).
      CONCLUSION: Serotonin overactivity is a putative cause of sexual dysfunction in
      patients with HSDD. The unique pharmacologic profile of flibanserin tones down
      inhibitory serotonergic function and restores dopaminergic and noradrenergic
      function. Croft HA. Understanding the Role of Serotonin in Female Hypoactive
      Sexual Desire Disorder and Treatment Options. J Sex Med 2017;14:1575-1584.

PMID- 29198513
TI  - The Vulvar Pain Assessment Questionnaire: Factor Structure, Preliminary Norms,
      Internal Consistency, and Test-Retest Reliability.
AB  - BACKGROUND: The Vulvar Pain Assessment Questionnaire (VPAQ) was developed to
      assist in the assessment and diagnosis of chronic vulvar pain (vulvodynia). AIM:
      To further establish the psychometric properties of the VPAQ by examining factor
      structure, test-retest reliability, internal consistency, and scale normative
      data, and to gather feedback from those with vulvar pain about the usefulness and
      accessibility of the questionnaire. METHODS: 182 participants completed a
      confidential online study and 70 participated again at time 2 (4 weeks later).
      OUTCOMES: Participants were asked to complete the full VPAQ, which assesses pain
      characteristics, effects on various parts of their lives, coping strategies used,
      and romantic partner factors. Additional questions captured sociodemographics and
      feedback about the instrument. RESULTS: Exploratory structural equation modeling
      indicated that the previously established subscales, except the coping scale, had
      adequate model fit, and all items loaded significantly onto relevant factors.
      Pearson product moment correlations (r = 0.57-0.96) established strong 4-week
      test-retest reliability for most subscale scores, and Cronbach alpha indicated
      overall acceptable to high internal consistency (alpha = 0.56-0.95). Preliminary
      norms for the scales are supplied. Approximately half the participants reported
      an increase in their comfort level in discussing a range of topics after
      completing the VPAQ. Most participants reported that the length, readability, and
      range of VPAQ questions were "good" or "excellent." CLINICAL IMPLICATIONS: The
      results of this study provide further justification for using the VPAQ scales in
      clinical and research settings, preliminary norms for a vulvar pain population,
      and suggestions for interpretation. STRENGTHS AND LIMITATIONS: This study
      established the psychometric properties of the VPAQ scales using multiple methods
      at 2 time points and gathered feedback from participants. However, data were
      collected online so diagnoses could not be confirmed and more than half the
      initial sample did not complete the survey at time 2. CONCLUSION: The results of
      this study suggest that most VPAQ subscales (except the coping subscale) have
      moderate to strong psychometric properties and that the VPAQ is user friendly.
      Dargie E, Holden RR, Pukall CF. The Vulvar Pain Assessment Questionnaire: Factor
      Structure, Preliminary Norms, Internal Consistency, and Test-Retest Reliability.
      J Sex Med 2017;14:1585-1596.

PMID- 29198515
TI  - Metacognitive Therapy Trial for Hypoactive Sexual Desire Disorder Breaks the
      Mold.

PMID- 29198514
TI  - Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors:
      A Pharmacoepidemiologic Study.
AB  - BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future
      cardiovascular disease and has been described as providing a "window of
      curability" for men to receive targeted cardiovascular risk assessment. AIM: To
      determine whether the prescription of phosphodiesterase type 5 inhibitors
      (PDE5is) for ED leads to the detection and treatment of previously undiagnosed
      cardiometabolic risk factors. METHODS: We performed a retrospective population
      based cohort study of residents of British Columbia, Canada using linked health
      care databases from 2004 to 2011. An individual-level time series analysis with
      switching replications was used to determine changes in drug use for
      hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The
      observation window for each patient was 720 days before and 360 days after the
      index date. OUTCOMES: The primary outcome was changes in prescriptions for
      antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes
      being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40
      to 59 years old newly prescribed a PDE5i were included in the analysis. We found
      a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P <
      .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P
      = .002) in the 90 days after a new prescription for a PDE5i. For
      hypercholesterolemia and diabetes, most of this change was observed in men with
      relevant screening tests performed in the 30 days after their PDE5i prescription.
      Only 15% and 17% of men who did not have a screening test for cholesterol and
      glucose, respectively, in the year before their PDE5i prescription went on to
      have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of
      screening tests observed in our study after PDE5i prescriptions suggests that
      physicians should be educated on the recommended screening guidelines for men
      newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were
      ordered a laboratory test or written a prescription but chose not to complete or
      fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can
      be a trigger or "gateway drug" for the early detection and treatment of
      cardiometabolic risk factors provided physicians perform the requisite screening
      investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction
      Medications and Treatment for Cardiometabolic Risk Factors: A
      Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.

PMID- 29198516
TI  - Erratum.

PMID- 29198517
TI  - Choice of resuscitative fluids and mortality in emergency department patients
      with sepsis.
AB  - OBJECTIVE: Balanced resuscitative fluids (BF) have been associated with decreased
      incidence of hyperchloremic metabolic acidosis in sepsis. We hypothesized that
      higher proportions of BF during resuscitation would thus be associated with
      improved mortality in Emergency Department (ED) patients with sepsis. METHODS:
      This was a retrospective chart review of adult ED patients who presented with
      sepsis to a large, urban teaching hospital over one year. The choice of
      resuscitation fluid in the first 2days of hospitalization was defined as either
      normal saline (NS) or balanced fluids (BF; Lactated Ringer's or Isolyte). The
      primary study outcome was in-hospital mortality, which was analyzed with
      multivariable logistic regression based on the proportion of BF received during
      the initial ED resuscitation. RESULTS: Of 149 patients screened, 33 were
      excluded, leaving 115 for analysis, of whom 18 died (16% overall mortality).
      Sixty-one (53%) patients received BF and NS, 6 (5%) patients received BF
      exclusively, while 48 (42%) patients received NS only. The mean number of liters
      administered was 5.4, and the mean percentage of BF administered was 29%. In
      univariate analysis, a higher proportion of BF was associated with lower odds of
      mortality (OR 0.973 [95% CI 0.961-0.986], p=0.00003). This association held true
      in multivariable models controlling for comorbidities and admission lactate
      level. CONCLUSIONS: We found that the proportion of BF during the initial ED
      resuscitation in septic patients was associated with a significant reduction in
      mortality. This association provides the necessary rationale for future
      randomized clinical trials of BF resuscitation in sepsis.

PMID- 29198518
TI  - The interplay between autonomic imbalance, cardiac dysfunction, and blood
      pressure variability in sepsis.

PMID- 29198519
TI  - Selective directed forgetting in children.
AB  - When, after study of an item list, adults are cued to forget some of the list
      items and encode new information instead, such cuing often induces selective
      forgetting of the to-be-forgotten material without impairing recall of the other
      items. This study examined developmental trends in such selective directed
      forgetting by having second graders, sixth graders, and young adults study three
      successive lists of items and, after study of List 2, cuing them either to
      remember both List 1 and List 2 or to forget List 2 but remember List 1.
      Consistent with prior work, second graders exhibited no forgetting at all in
      response to the forget cue, whereas young adults selectively forgot List 2. Sixth
      graders showed still another pattern with forgetting of both List 1 and List 2,
      suggesting that the ability to selectively forget is still absent at this age
      level. Directed forgetting has often been attributed to the action of inhibitory
      control processes. On the basis of this view, the current finding that children
      during middle childhood do not yet show selective forgetting indicates that the
      control processes underlying selective directed forgetting mature into
      adolescence and early adulthood.

PMID- 29198520
TI  - [Socioeconomic inequalities and kidney transplantation].
AB  - Studies at the population level must take into account the effect of social
      insecurity and socioeconomic inequalities on the patient outcomes. Socioeconomic
      inequalities depend on many determinants that are socially determined. In renal
      transplantation, these social determinants are not registered in the databases.
      The European Deprivation Index (EDI) is a composite index of social vulnerability
      with a French version. The EDI is an ecological measure of deprivation including
      the individual perception of basic needs for daily life that is called
      "subjective poverty". The Townsend index, Carstairs index and the Index of
      Multiple Deprivation are other ecological index available. It has been
      demonstrated in the United States that socioeconomic indicators of deprivation
      were associated with both the access to the waiting list for renal
      transplantation and transplantation failure. In France, socioeconomic deprivation
      may also affect the access to the waiting list and outcome of transplantation.
      This article is a review about deprivation and renal transplantation.

PMID- 29198521
TI  - Improving the surface properties of municipal solid waste-derived pyrolysis
      biochar by chemical and thermal activation: Optimization of process parameters
      and environmental application.
AB  - Biochar produced from the slow pyrolysis of municipal solid waste was activated
      with KOH and thermal treatments to enhance its surface and adsorptive properties.
      The effects of KOH concentration, activation temperature and time on the specific
      surface area (SSA) of the activated biochar were evaluated and optimized using
      central composite design (CCD) of the response surface methodology (RSM). Results
      showed that the activation of biochar enhanced its SSA from 402.8 +/- 12.5 to
      662.4 +/- 28.6 m2 g-1. The adsorptive capacities of the pristine biochar (PBC)
      and activated biochar (ABC) were compared using methylene blue (MB) dye as model
      compound. For MB concentrations up to 25 mg L-1, more than 99% dye removal was
      achieved with ABC, while only a maximum of 51% was obtained with PBC. Results of
      the isotherm study showed that the Langmuir model best described MB adsorption on
      ABC with adsorption capacity of 37.0-41.2 mg g-1.

PMID- 29198522
TI  - Role of compostable tableware in food service and waste management. A life cycle
      assessment study.
AB  - It is estimated that in Europe 88-100 million tonnes of food waste are generated
      every year, with a Global Warming Potential (GWP) of around 227 MT of CO2
      equivalents generated for their collection and disposal. A 12% of this waste is
      estimated to arise from food service within the hospitality sector, which
      includes quick service restaurants, casual and fine dining, contract catering
      (canteens, prisons, hospitals, schools etc.) as well as indoor and outdoor events
      and exhibitions. Given this considerable amount and that the mixed unsorted
      collection is often the only practicable way to handle such waste flows, the
      choice of tableware and cutlery can make a big difference in facilitating waste
      collection as well as in reducing the overall environmental impact of food waste
      management. This study compares the environmental performance of using
      biodegradable & compostable single use tableware with organic recycling of food
      waste through composting against a traditional scenario using fossil-based
      plastic tableware and disposal of the waste flows through incineration and
      landfill. The study has taken into account the main requirements of the recently
      published Product Environmental Footprint (PEF) methodology of the European
      Commission. The results confirm that the use of biodegradable and compostable
      tableware combined with organic recycling is the preferred option for catering in
      quick service restaurants, contract catering and events, since it reduces
      significantly the carbon, water and resource footprint and is fully in line with
      the principles of a circular economy.

PMID- 29198523
TI  - Resetting the Yeast Epigenome with Human Nucleosomes.
AB  - Humans and yeast are separated by a billion years of evolution, yet their
      conserved histones retain central roles in gene regulation. Here, we "reset"
      yeast to use core human nucleosomes in lieu of their own (a rare event taking 20
      days), which initially only worked with variant H3.1. The cells adapt by
      acquiring suppressor mutations in cell-division genes or by acquiring certain
      aneuploid states. Converting five histone residues to their yeast counterparts
      restored robust growth. We reveal that humanized nucleosomes are positioned
      according to endogenous yeast DNA sequence and chromatin-remodeling network, as
      judged by a yeast-like nucleosome repeat length. However, human nucleosomes have
      higher DNA occupancy, globally reduce RNA content, and slow adaptation to new
      conditions by delaying chromatin remodeling. These humanized yeasts (including
      H3.3) pose fundamental new questions about how chromatin is linked to many cell
      processes and provide a platform to study histone variants via yeast epigenome
      reprogramming.

PMID- 29198524
TI  - Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in
      Head and Neck Cancer.
AB  - The diverse malignant, stromal, and immune cells in tumors affect growth,
      metastasis, and response to therapy. We profiled transcriptomes of ~6,000 single
      cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including
      five matched pairs of primary tumors and lymph node metastases. Stromal and
      immune cells had consistent expression programs across patients. Conversely,
      malignant cells varied within and between tumors in their expression of
      signatures related to cell cycle, stress, hypoxia, epithelial differentiation,
      and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p
      EMT program spatially localized to the leading edge of primary tumors. By
      integrating single-cell transcriptomes with bulk expression profiles for hundreds
      of tumors, we refined HNSCC subtypes by their malignant and stromal composition
      and established p-EMT as an independent predictor of nodal metastasis, grade, and
      adverse pathologic features. Our results provide insight into the HNSCC ecosystem
      and define stromal interactions and a p-EMT program associated with metastasis.

PMID- 29198525
TI  - A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded
      Protein Response.
AB  - When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded
      protein response (UPR) increases ER-protein-folding capacity to restore protein
      folding homeostasis. Unfolded proteins activate UPR signaling across the ER
      membrane to the nucleus by promoting oligomerization of IRE1, a conserved
      transmembrane ER stress receptor. However, the coupling of ER stress to IRE1
      oligomerization and activation has remained obscure. Here, we report that the ER
      luminal co-chaperone ERdj4/DNAJB9 is a selective IRE1 repressor that promotes a
      complex between the luminal Hsp70 BiP and the luminal stress-sensing domain of
      IRE1alpha (IRE1LD). In vitro, ERdj4 is required for complex formation between BiP
      and IRE1LD. ERdj4 associates with IRE1LD and recruits BiP through the stimulation
      of ATP hydrolysis, forcibly disrupting IRE1 dimers. Unfolded proteins compete for
      BiP and restore IRE1LD to its default, dimeric, and active state. These
      observations establish BiP and its J domain co-chaperones as key regulators of
      the UPR.

PMID- 29198526
TI  - Neuromodulatory Control of Long-Term Behavioral Patterns and Individuality across
      Development.
AB  - Animals generate complex patterns of behavior across development that may be
      shared or unique to individuals. Here, we examine the contributions of
      developmental programs and individual variation to behavior by monitoring single
      Caenorhabditis elegans nematodes over their complete developmental trajectories
      and quantifying their behavior at high spatiotemporal resolution. These
      measurements reveal reproducible trajectories of spontaneous foraging behaviors
      that are stereotyped within and between developmental stages. Dopamine,
      serotonin, the neuropeptide receptor NPR-1, and the TGF-beta peptide DAF-7 each
      have stage-specific effects on behavioral trajectories, implying the existence of
      a modular temporal program controlled by neuromodulators. In addition, a fraction
      of individuals within isogenic populations raised in controlled environments have
      consistent, non-genetic behavioral biases that persist across development.
      Several neuromodulatory systems increase or decrease the degree of non-genetic
      individuality to shape sustained patterns of behavior across the population.

PMID- 29198527
TI  - Effects of multiple breath-hold reproducibility on treatment localization and
      dosimetric accuracy in radiotherapy of left-sided breast cancer: Methodology and
      statistical issues in reproducibility and accuracy.

PMID- 29198528
TI  - An integrative review of the enjoyment of sadness associated with music.
AB  - The recent surge of interest towards the paradoxical pleasure produced by sad
      music has generated a handful of theories and an array of empirical explorations
      on the topic. However, none of these have attempted to weigh the existing
      evidence in a systematic fashion. The present work puts forward an integrative
      framework laid out over three levels of explanation - biological, psycho-social,
      and cultural - to compare and integrate the existing findings in a meaningful
      way. First, we review the evidence pertinent to experiences of pleasure
      associated with sad music from the fields of neuroscience, psychophysiology, and
      endocrinology. Then, the psychological and interpersonal mechanisms underlying
      the recognition and induction of sadness in the context of music are combined
      with putative explanations ranging from social surrogacy and nostalgia to
      feelings of being moved. Finally, we address the cultural aspects of the paradox 
      the extent to which it is embedded in the Western notion of music as an
      aesthetic, contemplative object - by synthesising findings from history,
      ethnography, and empirical studies. Furthermore, we complement these explanations
      by considering the particularly significant meanings that sadness portrayed in
      art can evoke in some perceivers. Our central claim is that one cannot attribute
      the enjoyment of sadness fully to any one of these levels, but to a chain of
      functionalities afforded by each level. Each explanatory level has several
      putative explanations and its own shift towards positive valence, but none of
      them deliver the full transformation from a highly negative experience to a fully
      enjoyable experience alone. The current evidence within this framework ranges
      from weak to non-existent at the biological level, moderate at the psychological
      level, and suggestive at the cultural level. We propose a series of focussed
      topics for future investigation that would allow to deconstruct the drivers and
      constraints of the processes leading to pleasurable music-related sadness.

PMID- 29198529
TI  - Can we identify others' intentions from seeing their movements? Comment on
      "Seeing mental states: An experimental strategy for measuring the observability
      of other minds" by Cristina Becchio et al.

PMID- 29198530
TI  - Hospitalizations for Ambulatory Care-Sensitive Conditions among Children with
      Chronic and Complex Diseases.
AB  - OBJECTIVE: To evaluate ambulatory-care sensitive (ACS) hospitalizations for
      children with noncomplex chronic diseases (NC-CD) and children with medical
      complexity (CMC), and identify associations with ambulatory care characteristics.
      Although ACS hospitalizations are potentially preventable in general populations,
      the specific ambulatory care predictors and influence of medical complexity on
      them is poorly understood. STUDY DESIGN: Retrospective cohort study of NC-CD and
      CMC hospitalizations at a children's hospital during 2007-2014, excluding
      labor/delivery and children over 21 years. Pediatric medical complexity algorithm
      identified NC-CD or CMC. ACS hospitalizations were identified using Agency for
      Healthcare Research and Quality indicator definitions. Demographic and ambulatory
      care characteristics were compared between ACS and non-ACS hospitalizations with
      logistic regression clustered by patient. Measures of ambulatory care during 2
      years before admission were explored with 20% random sample of general pediatrics
      discharges. RESULTS: Among 4035 children with NC-CD, 14.6% of 4926
      hospitalizations were ACS hospitalizations. Among 5084 CMC, 5.3% of 14 390
      discharges were ACS hospitalizations. Among NC-CD discharges, ACS
      hospitalizations were more likely with no prior-year outpatient visits (OR 1.4,
      95% CI 1.1-1.7) and less likely with timely well checks (OR 0.8, 95% CI 0.6-0.9)
      and phone encounters in the month before admission (OR 0.5, 95% CI 0.2-1.0).
      Among CMC discharges, the only association observed was with provider continuity
      (OR 0.3, 95% CI 0.1- 1.0). CONCLUSIONS: Provider continuity may be associated
      with fewer CMC ACS hospitalizations, however, measures of ambulatory care were
      more consistently associated with ACS hospitalizations for NC-CD. CMC may need
      more precise ACS hospitalization definitions.

PMID- 29198531
TI  - Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related
      Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic
      Adipocytokine Production.
AB  - OBJECTIVES: To investigate whether the modulation of local cellular cross-talks
      and the modification of hepatic adipocytokine expression could mechanistically
      explain the improvement of liver histopathology after laparoscopic sleeve
      gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD).
      STUDY DESIGN: Twenty obese (body mass index of >=35 kg/m2) adolescents who
      underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1
      year after treatment, patients underwent clinical evaluation, blood tests, and
      liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs),
      macrophages, and adipocytokines were evaluated by immunohistochemistry and
      immunofluorescence. RESULTS: Liver biopsy samples after LSG demonstrated a
      significant improvement of NAFLD Activity Score and fibrosis.
      Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle
      arrest, ductular reaction, activated HSC, and macrophage number after LSG
      compared with T0. The activation state of HSC was accompanied by modification in
      the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin
      was significant higher after LSG than into T0. Moreover, LSG caused decreased
      resistin expression in Sox9+ hepatic progenitor cells compared with T0. The
      number of S100A9+ macrophages was also reduced by LSG correlating with resistin
      expression. Finally, serum levels of proinflammatory cytokines significantly
      correlated with macrophages and activated HSC numbers. CONCLUSIONS: The
      histologic improvement induced by LSG is associated with the reduced activation
      of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages),
      thus, strengthening the role of cellular interactions and hepatic adipocytokine
      production in the pathogenesis of NAFLD.

PMID- 29198532
TI  - Impact of Prolonged Mechanical Ventilation in Very Low Birth Weight Infants:
      Results From a National Cohort Study.
AB  - OBJECTIVE: To evaluate the in-hospital consequences of prolonged respiratory
      support with invasive mechanical ventilation in very low birth weight infants.
      STUDY DESIGN: A cohort study was performed using prospectively collected data
      from 69 neonatal intensive care units participating in the Korean national
      registry. In total, 3508 very low birth weight infants born between January 1,
      2013 and December 31, 2014 were reviewed. RESULTS: The adjusted hazard ratio for
      death increased significantly for infants who received mechanical ventilation for
      more than 2 weeks compared with those were mechanically ventilated for 7 days or
      less. The individual mortality rate increased after 8 weeks, reaching 50% and 60%
      at 14 and 16 weeks of cumulative mechanical ventilation, respectively. After
      adjusting for potential confounders, the cumulative duration of mechanical
      ventilation was associated with a clinically significant increase in the odds of
      bronchopulmonary dysplasia and pulmonary hypertension. Mechanical ventilation
      exposure for longer than 2 weeks, compared with 7 days or less, was associated
      with retinopathy of prematurity requiring laser coagulation and periventricular
      leukomalacia. The odds of abnormal auditory screening test results were
      significantly increased in infants who needed mechanical ventilation for more
      than 4 weeks. A longer cumulative duration of mechanical ventilation was
      associated with increased lengths of hospitalization and parenteral nutrition and
      a higher probability of discharge with poor achievement of physical growth.
      CONCLUSIONS: Although mechanical ventilation is a life-saving intervention for
      premature infants, these results indicate that it is associated with negative
      consequences when applied for prolonged periods.

PMID- 29198533
TI  - Usefulness of Routine Transtelephonic Monitoring for Supraventricular Tachycardia
      in Infants.
AB  - OBJECTIVE: We hypothesize that routine daily transtelephonic monitoring (TTM)
      transmissions can accurately detect supraventricular tachycardia (SVT) in
      asymptomatic infants and/or assuage parental concerns rather than being used
      solely to diagnose arrhythmias. STUDY DESIGN: Single center, retrospective chart
      review of 60 patients with fetal or infant SVT prescribed TTM for at least 30
      days, January 2010-September 2016. Patients were excluded if initial SVT was not
      documented, was perioperative, was atrial flutter/fibrillation, or chaotic atrial
      tachycardia. Categorical variables expressed as mean +/- SD. Mann-Whitney,
      Spearman correlation, and Fisher exact tests were used for continuous and
      categorical variables respectively. RESULTS: Sixty patients were included. There
      were 2688 TTM transmissions received from 55 of 60 patients over 61.1 +/- 66.7
      days (0.73 +/- 0.65 TTM/patient/days). Routine asymptomatic TTM transmissions
      revealed actionable findings in 5 of 2801 TTM transmissions sent by 5 patients
      (8.3%). No patient presented in shock or died. Forty-five of 2688 TTM
      transmissions were sent for parental concerns/symptoms in 16 patients (25.8%)
      with findings of normal sinus rhythm in 37 of 45 TTM transmissions and SVT in 8
      of 45 TTM transmissions. Symptomatic actionable findings were more likely sent by
      patients discharged on class I or III antiarrhythmics (95% CI = 11.5%-68.3%, P =
      .004) and patients with prolonged initial hospitalizations (95% CI = 6.98%-59.7%,
      P = .01). Flecainide was discontinued in 1 patient after widened QRS was noted on
      routine TTM. CONCLUSIONS: TTM accurately diagnose asymptomatic recurrent SVT in
      neonates and infants before they develop signs of congestive heart failure or
      shock and is helpful for recurrent SVT management.

PMID- 29198534
TI  - An Intragastric Fecal Microbiota Transplantation Program for Treatment of
      Recurrent Clostridium difficile in Children is Efficacious, Safe, and
      Inexpensive.
AB  - OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led
      fecal microbiota transplantation (FMT) program for the treatment of recurrent
      Clostridium difficile infection (CDI). STUDY DESIGN: Retrospective cohort study
      design in children aged 1-18 years with recurrent CDI. The intervention was an
      intragastric FMT with stool derived from a donor stool bank. Primary outcome was
      resolution of diarrhea at 3 months post-transplantation. A secondary analysis
      compared charge data associated with FMT by intragastric delivery vs
      administration by colonoscopy or nasoduodenal tube. RESULTS: A total of 47
      intragastric FMT procedures were performed in 42 children (median age 9 years)
      with recurrent CDI. Response to treatment varied by disease status, with 94%
      success in previously healthy children, 75% in medically complex children, and
      54% in children with inflammatory bowel disease (P = .04). FMT via intragastric
      delivery showed lower facility and professional charges by 85% and 78% compared
      with delivery via colonoscopy and radiology-placed nasoduodenal tube,
      respectively. The use of stool derived from a donor stool bank decreased charges
      by 49% compared with charges associated with the use of a donor who was a
      relative. CONCLUSION: A nurse-led intragastric FMT procedure using stool derived
      from a donor stool bank is a relatively inexpensive and efficacious treatment for
      recurrent CDI in children. Intragastric FMT success in children was attenuated by
      the presence of underlying disease, particularly inflammatory bowel disease.

PMID- 29198535
TI  - Resistance of the interface device used to deliver nasal continuous positive
      airway pressure or nasal intermittent ventilation.

PMID- 29198537
TI  - Healthcare Utilization and Comorbidities Associated with Anorectal Malformations
      in the United States.
AB  - OBJECTIVE: To determine nationwide prevalence and healthcare utilization in
      children with anorectal malformations and associated anomalies over a 6-year
      period. STUDY DESIGN: We used the Kids' Inpatient Database for the years 2006,
      2009, and 2012 for data collection. International Classification of Diseases,
      Ninth Revision codes were used to identify patients with anorectal malformations
      and associated anomalies. RESULTS: A total of 2396 children <2 years of age with
      anorectal malformations were identified using weighted analysis; 54.3% of
      subjects were male. The ethnic subgroups were 40.1% white, 23.6% Hispanic, 9.3%
      African American, and 27% other ethnicity. Other congenital anomalies were
      reported in 80% of anorectal malformations and were closely associated with
      increased length of stay and costs. A genetic disorder was identified in 14.1% of
      the sample. Urogenital anomalies were present in 38.5%, heart anomalies in 21.2%,
      and 8.6% had vertebral anomalies, anal atresia, cardiac defects,
      tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and limb
      defects association. Anorectal malformations with other anomalies including
      vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula
      and/or esophageal atresia, renal anomalies, and limb defects association incurred
      significant hospital charges when compared with anorectal malformations alone.
      The average annual healthcare expenditure for surgical correction of anorectal
      malformations and associated anomalies for the 3 years was US $45.5 million.
      CONCLUSIONS: This large, major nationally representative study shows that
      majority of children with anorectal malformations have additional congenital
      anomalies that deserve prompt recognition. The high complexity and need for
      lifelong multidisciplinary management is associated with substantial healthcare
      expenditure. This information complements future healthcare resource allocation
      and planning for management of children with anorectal malformations.

PMID- 29198536
TI  - Infants with Atypical Presentations of Alveolar Capillary Dysplasia with
      Misalignment of the Pulmonary Veins Who Underwent Bilateral Lung Transplantation.
AB  - OBJECTIVE: To describe disease course, histopathology, and outcomes for infants
      with atypical presentations of alveolar capillary dysplasia with misalignment of
      the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. STUDY
      DESIGN: We reviewed clinical history, diagnostic studies, explant histology,
      genetic sequence results, and post-transplant course for 6 infants with atypical
      ACDMPV who underwent bilateral lung transplantation at St. Louis Children's
      Hospital. We compared their histology with infants with classic ACDMPV and
      compared their outcomes with infants transplanted for other indications. RESULTS:
      In contrast with neonates with classic ACDPMV who present with severe hypoxemia
      and refractory pulmonary hypertension within hours of birth, none of the infants
      with atypical ACDMPV presented with progressive neonatal respiratory failure.
      Three infants had mild neonatal respiratory distress and received nasal cannula
      oxygen. Three other infants had no respiratory symptoms at birth and presented
      with hypoxemia and pulmonary hypertension at 2-3 months of age. Bilateral lung
      transplantation was performed at 4-20 months of age. Unlike in classic ACDMPV,
      histopathologic findings were not distributed uniformly and were not diffuse.
      Three subjects had apparent nonmosaic genetic defects involving FOXF1. Two
      infants had extrapulmonary anomalies (posterior urethral valves, inguinal
      hernia). Three transplanted children are alive at 5-16 years of age, similar to
      outcomes for infants transplanted for other indications. Lung explants from
      infants with atypical ACDMPV demonstrated diagnostic but nonuniform
      histopathologic findings. CONCLUSIONS: The 1- and 5-year survival rates for
      infants with atypical ACDMPV are similar to infants transplanted for other
      indications. Given the clinical and histopathologic spectra, ACDMPV should be
      considered in infants with hypoxemia and pulmonary hypertension, even beyond the
      newborn period.

PMID- 29198538
TI  - A Nonlethal Case of Junctional Epidermolysis Bullosa and Congenital Pyloric
      Atresia: Compound Heterozygosity in a Patient with a Novel Integrin Beta 4 Gene
      Mutation.
AB  - We report a case of nonfatal junctional epidermolysis bullosa and pyloric atresia
      in a newborn. We identified a substitution (c.914C>T) for the integrin beta4 gene
      that has been associated with favorable outcome. A novel mutation (c.2011T>G) of
      unknown significance was also found in this patient who is now thriving.

PMID- 29198539
TI  - Long-Term Outcomes of Hyperglycemic Preterm Infants Randomized to Tight Glycemic
      Control.
AB  - OBJECTIVE: To determine whether tight glycemic control of neonatal hyperglycemia
      changes neurodevelopment, growth, and metabolism at school age. STUDY DESIGN:
      Children born very low birth weight and randomized as hyperglycemic neonates to a
      trial of tight vs standard glycemic control were assessed at 7 years corrected
      age, including Wechsler Intelligence Scale for Children Fourth Edition, Movement
      Assessment Battery for Children 2, visual and neurologic examinations, growth
      measures, dual X-ray absorptiometry, and frequently sampled intravenous glucose
      tolerance test. The primary outcome was survival without neurodevelopmental
      impairment at age 7 years. Outcomes were compared using linear regression,
      adjusted for sex, small for gestational age, birth plurality, and the clustering
      of twins. Data are reported as number (%) or mean (SD). RESULTS: Of the 88
      infants randomized, 11 (13%) had died and 57 (74% of eligible children) were
      assessed at corrected age 7 years. Survival without neurodevelopmental impairment
      occurred in 25 of 68 children (37%), with no significant difference between tight
      (14 of 35; 40%) and standard (11 of 33; 33%) glycemic control groups (P = .60).
      Children in the tight group were shorter than those in the standard group (121.3
      [6.3] cm vs 125.1 [5.4] cm; P < .05), but had similar weight and head
      circumference. Children in the tight group had greater height-adjusted lean mass
      (18.7 [0.3] vs 17.6 [0.2] kg; P < .01) and lower fasting glucose concentrations
      (84.6 [6.30] vs 90.0 [5.6] mg?dL-1; P < .05), but no other differences in
      measures of body composition or insulin-glucose metabolism. CONCLUSION: Tight
      glycemic control for neonatal hyperglycemia does not change survival without
      neurodevelopmental impairment, but reduces height, increases height-adjusted lean
      mass, and reduces fasting blood glucose concentrations at school age. TRIAL
      REGISTRATION: ACTRN: 12606000270516.

PMID- 29198540
TI  - Severity and Features of Epistaxis in Children with a Mucocutaneous Bleeding
      Disorder.
AB  - OBJECTIVE: To use standardized bleeding questionnaires to compare the severity
      and patterns of epistaxis in children with a mucocutaneous bleeding disorder and
      control children. STUDY DESIGN: The epistaxis sections of the Pediatric Bleeding
      Questionnaire (PBQ) administered to pediatric patients with von Willebrand
      disease or a platelet function disorder and healthy control children were
      reviewed. Scores and features of epistaxis (frequency, duration, onset, site,
      seasonal correlation, and need for medical/surgical intervention) were recorded.
      A PBQ epistaxis score >=2 was defined as clinically significant. The Katsanis
      epistaxis scoring system was administered to eligible patients, ie, with >=5
      episodes of epistaxis per year. RESULTS: PBQ epistaxis scores were obtained for
      66 patients, median age 12 years (range 0.6-18.3 years), and 56 control children.
      The median PBQ epistaxis score in patients was 2 vs 0 in control children (P
      <.0001). All of the features of epistaxis, except spontaneous onset, occurred in
      a significantly greater proportion of patients than control children with
      epistaxis. A total of 50% of the patients were graded as having severe epistaxis
      by the Katsanis epistaxis scoring system, and 30 of these (91%) had a clinically
      significant PBQ epistaxis score. CONCLUSION: Standardized bleeding questionnaires
      are useful in the assessment of epistaxis severity and pattern and may help to
      distinguish children with and without a mucocutaneous bleeding disorder.

PMID- 29198541
TI  - Returning Adolescents to Driving after Sports-Related Concussions: What
      Influences Physician Decision-Making.
AB  - OBJECTIVE: To determine which data collected on an initial patient clinic visit
      for a sports-related concussion (SRC) might influence physicians to clear an
      adolescent to return to drive (RTD) after injury. STUDY DESIGN: Retrospective
      cohort study of 189 adolescents with a SRC referred to a hospital-based
      concussion clinic between June 1, 2015, and May 31, 2016. Subjects were >=16
      years with a valid driver's license (median age = 16, IQR [16, 17]). Concussion
      evaluations included Post-Concussion Symptom Scale, modified Balance Error
      Scoring System, and postinjury computerized neurocognitive testing (CNT).
      Clearance for RTD was the main outcome. Statistical comparisons were conducted
      with Mann-Whitney U and chi2 tests and logistic regression. RESULTS: In
      multivariable analysis, odds of being fully cleared to drive were 5.9-fold
      greater among patients who were administered CNT. Stated symptoms of "headache"
      and "sensitivity to light" were statistically significantly associated with RTD
      clearance. For a subset of 113 individuals undergoing CNT, each additional 10
      millisecond decrease in simple reaction time was associated with 9% greater odds
      of being cleared to drive. Each additional 10-millisecond decrease in choice
      reaction time was associated with 4% greater odds of being cleared to drive.
      CONCLUSIONS: CNT and associated reaction time measures may facilitate a
      physician's objective decision-making. Making a RTD determination for adolescents
      recovering from an SRC should be a core component of a physician's assessment.

PMID- 29198542
TI  - Kawasaki Disease Substantially Impacts Health-Related Quality of Life.
AB  - OBJECTIVE: To prospectively evaluate the acute impact of Kawasaki disease (KD) on
      health-related quality of life (HRQoL) and to assess deterioration in the HRQoL
      experienced by children with KD compared with other childhood diseases. STUDY
      DESIGN: We merged the Outcomes Assessment Program database obtained prospectively
      with the existing KD database and queried for KD admissions between 1 month and
      13 years of age. HRQoL was evaluated with the parent-proxy Pediatric Quality of
      Life Inventory (PedsQL) 4.0 Generic Core and Infant Scales. We compared the KD
      HRQoL results with those obtained from newly diagnosed patients with cancer and
      pneumonia, matched for age, sex and race. PedsQL total scores over time were
      assessed with ANCOVA models, adjusted for matching variables and PedsQL score
      prior to admission. RESULTS: We identified 89 patients with KD and compared 65
      subjects with an equal number with pneumonia and with 67 subjects with newly
      diagnosed cancer. Patients with demonstrated lower PedsQL total score on
      admission and suffered a significantly greater HRQoL decline from baseline to
      admission than the other groups. KD diagnostic subtype (complete or incomplete)
      and coronary artery dilatation were not associated with HRQoL outcomes. However,
      non-intravenous immunoglobulin responders showed greater HRQoL decline than
      responders (P = .03). CONCLUSIONS: Children with KD suffer acute and significant
      HRQoL impairment exceeding that of children newly diagnosed with cancer. Lack of
      immediate treatment response may exert an additional HRQoL burden, whereas KD
      subtype and coronary artery dilatation do not.

PMID- 29198544
TI  - Hepatic Vascular Tumors in the Neonate: Angiosarcoma.

PMID- 29198543
TI  - Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm
      Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin
      Counteracts This Effect.
AB  - OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such
      as H2 blockers or proton pump inhibitors, can independently increase the risk of
      infections in very low birth weight (VLBW) preterm infants in the neonatal
      intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively
      collected data from a multicenter, randomized controlled trial of bovine
      lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus
      rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing
      enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used
      at the recommended dosages/schedules based on the clinical judgment of attending
      physicians. The distribution of days of inhibitors of gastric acidity exposure
      between infants with and without LOS/NEC was assessed. The mutually adjusted
      effects of birth weight, gestational age, duration of inhibitors of gastric
      acidity treatment, and exposure to BLF were controlled through multivariable
      logistic regression. Interaction between inhibitors of gastric acidity and BLF
      was tested; the effects of any day of inhibitors of gastric acidity exposure were
      then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty
      five of 743 infants underwent treatment with inhibitors of gastric acidity, and
      86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of
      gastric acidity remained significantly and independently associated with LOS (OR,
      1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity
      exposure conferred an additional 3.7% odds of developing LOS. Risk was
      significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not
      for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional
      day of exposure to inhibitors of gastric acidity conferred an additional 7.7%
      risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in
      BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is
      significantly associated with the occurrence of LOS in preterm VLBW infants.
      Concomitant administration of BLF counteracts this selective disadvantage. TRIAL
      REGISTRATION: isrctn.org: ISRCTN53107700.

PMID- 29198545
TI  - Burden of Poor Health Conditions and Quality of Life in 656 Children with Primary
      Immunodeficiency.
AB  - OBJECTIVE: To gain insight into how primary immunodeficiencies (PIDs) affect
      children's health status and quality of life. STUDY DESIGN: The French Reference
      Center for PIDs conducted a prospective multicenter cohort that enrolled
      participants who met all criteria: patients included in the French Reference
      Center for PIDs registry, children younger than18 years, and living in France.
      Participants were asked to complete both a health questionnaire and a health
      related quality of life (HR-QoL) questionnaire. A severity score was assigned to
      each health condition: grade 1 (mild) to grade 4 (life-threatening). HR-QoL in
      children was compared with age- and sex-matched French norms. RESULTS: Among 1047
      eligible children, 656 were included in the study, and 117 had undergone
      hematopoietic stem cell transplantation; 40% experienced at least one grade 4
      condition, and 83% experienced at least one grade 3 or 4 condition. Compared with
      the French norms, children with PID scored significantly lower for most HR-QoL
      domains. Low HR-QoL scores were associated strongly with burden of poor
      conditions. CONCLUSIONS: Our results quantify the magnitude of conditions in
      children with PID and demonstrate that the deleterious health effects borne by
      patients already are evident in childhood. These results emphasize the need to
      closely monitor this vulnerable population and establish multidisciplinary
      healthcare teams from childhood. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT02868333 and EudraCT 2012-A0033-35.

PMID- 29198546
TI  - Lack of experience is a significant factor in the missed diagnosis of perilunate
      fracture dislocation or isolated dislocation.
AB  - OBJECTIVE: The aim of this study was to analyze the risk factors contributing to
      the misdiagnosis of perilunate injuries. METHODS: The study included patients who
      had perilunate dislocation or fracture dislocation correctly or incorrectly
      diagnosed on initial examination between 2008 and 2014. Data related to the
      length of time until correct diagnosis of the perilunate injury; cause of injury;
      presence of associated fractures, polytrauma or concomitant trauma in the
      ipsilateral upper extremity; time between injury and first presentation; first
      treatment applied; presence of ligamentous perilunar injuries only or fracture
      and dislocation; inadequate radiographic assessment; and experience of the
      physicians were recorded and analyzed. RESULTS: A total of 44 wrists were
      included in the study. Of those, 10 (22.7%) wrists (mean patient age: 44.4 years
      [28 +/- 58 years]) with perilunate injuries were misdiagnosed in the initial
      evaluation. All of the risk factors were found to be similar between the group of
      patients with correct initial diagnosis and missed diagnosis group, except for
      the experience of the orthopedic surgeon assessing the injury (p = 0.0001). Of
      the surgeons who missed the diagnosis, 70% reported that it was their first
      encounter with a perilunate injury. CONCLUSION: The results of this study
      indicated that lack of experience was the most important factor in the
      misdiagnosis of perilunate fracture dislocation or isolated dislocation. LEVEL OF
      EVIDENCE: Level IV, diagnostic study.

PMID- 29198547
TI  - Pelvic organ prolapse.

PMID- 29198548
TI  - Embolization of arterial gastrointestinal hemorrhage with Fuaile medical
      adhesive.
AB  - BACKGROUND: To investigate the safety and effectiveness of Fuaile medical
      adhesive (FAL) with superselective catheterization in endovascular embolotherapy
      for the treatment of gastrointestinal hemorrhage (GIH) that was unresponsive to
      internal medicine treatment and gastroscopy management. METHODS: A total of 25
      patients with GIH, confirmed using angiography but with failed results after
      internal medicine treatment or gastroscopy were retrospectively analyzed. A
      mixture of lipiodol and FAL (1:1) was used to embolize the bleeding vessels. In
      the follow-up, the operation time, FAL amount, technical success rate, clinical
      success rate, postoperative complications, and survival conditions were compared
      and analyzed. RESULTS: Among the 25 patients with GIH, FAL was applied alone in
      23 patients and microcoil combined with FAL was applied in two patients.
      Hemostasis was successfully achieved in all patients. Two patients treated with
      embolotherapy experienced relapse of bleeding within 30 days but achieved
      successful hemostasis with FAL. Four patients died during follow-up: three
      patients died of advanced cancer and one patient died of severe infection induced
      by necrotizing pancreatitis. Three patients developed postoperative intestinal
      ischemic symptoms, which resolved spontaneously in two patients. In one patient,
      abdominal pain progressively aggravated. This patient underwent surgical
      resection, which confirmed the presence of colonic neoplasms. The intraoperative
      view revealed obvious ischemia of the local normal bowel near the tumor; however,
      the patient finally recovered and was discharged after surgery. The remaining
      patients exhibited good survival during the postoperative follow-up. CONCLUSION:
      FAL embolotherapy has a high success rate for arterial GIH that was unresponsive
      to internal medicine treatment and gastroscopy management, with low postoperative
      rates of bleeding and complications; thus, this method has a high cost-efficacy.

PMID- 29198549
TI  - Development and validation of a Taiwan version of the ID Pain questionnaire (ID
      Pain-T).
AB  - BACKGROUND: Neuropathic pain (NeP) is distinct from nociceptive pain and has
      different underlying mechanisms requiring specific treatment strategies. To aid
      diagnosis, self-administered screening questionnaires (such as ID Pain) have been
      developed to help physicians identify patients with NeP. The aim of this study
      was to develop and validate a translated ID Pain questionnaire for Taiwanese
      subjects (ID Pain-T). METHODS: ID Pain, a 6-item self-administered questionnaire,
      score ranged from -1 to 5, was translated from English into Mandarin Chinese
      using local terms and back-translated by an expert panel. A prospective, non
      randomized, multi-center study was performed in four medical centers in Taiwan.
      Patients aged over 18 years with pain other than headache for more than 30 days
      in either neurology or pain clinic were prospectively recruited. They completed
      the ID Pain-T questionnaire themselves. The study investigators, blinded to the
      subjects' ID Pain-T scores, examined subjects using a standardized clinical and
      neurological diagnostic procedure. The ID Pain-T questionnaire scores were
      verified and validated. RESULTS: A total of 317 patients completed the study.
      Clinical diagnosis of NeP was given for 189 (60%) patients, mixed pain diagnosed
      in 7 (2%) patients, and nociceptive pain in 121 (38%) patients. The reliability
      and consistency of the ID Pain-T were acceptable, with a Cronbach's alpha value
      of 0.6. Statistical analysis of the ID Pain-T questionnaire calculated an optimal
      cut-off score of >=2 for determining NeP with 77% sensitivity and 74% specificity
      for predicting NeP. Ordinary least squares regression analysis showed significant
      predictive accuracy of the ID Pain-T questionnaire for NeP (P < 0.0001). These
      results are comparable to other studies that have translated the ID Pain
      questionnaire into other languages. CONCLUSION: This study provides evidence that
      the ID Pain-T questionnaire is a valid and reliable self-administered screening
      tool to identify NeP in Taiwanese patients.

PMID- 29198550
TI  - The susceptibility of anti-tuberculosis drug-induced liver injury and chronic
      hepatitis C infection: A systematic review and meta-analysis.
AB  - BACKGROUND: Anti-tuberculosis drug-induced liver injury (ATDILI) is a major
      safety concern in the treatment of tuberculosis (TB). The impact of chronic
      hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We
      aimed to assess the influence of CHC infection on ATDILI through a systematic
      review and meta-analysis. METHODS: We systemically reviewed all English-language
      literature in the major medical databases with the subject search terms "anti
      tuberculosis drug-induced liver injury" and "anti-tuberculosis drug-induced
      hepatotoxicity". We then performed a systematic review and meta-analysis of the
      papers relevant to hepatitis C in qualified publications. RESULTS: A total of 14
      studies were eligible for analysis, which included 516 cases with ATDILI and 4301
      controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC
      infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30-4.49). Subgroup
      analysis revealed that the CHC carriers had a higher risk of ATDILI than those
      without CHC both in Asians (OR = 2.96, 95% CI: 1.79-4.90) and Caucasians (OR =
      4.07, 95% CI: 2.70-6.14), in those receiving standard four combination anti-TB
      therapy (OR = 2.94, 95% CI: 1.95-4.41) and isoniazid monotherapy (OR = 4.18, 95%
      CI: 2.36-7.40), in those with a strict definition of DILI (serum alanine
      aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI:
      1.58-4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI:
      2.96-6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93-5.90) and case
      control studies (OR = 2.43, 95% CI: 1.29-4.58). CONCLUSION: This meta-analysis
      suggests that CHC infection may increase the risk of ATDILI. Regular liver tests
      are mandatory for CHC carriers under anti-TB therapy.

PMID- 29198551
TI  - Experience of double balloon enteroscopy.
AB  - BACKGROUND: To evaluated the experiences of double balloon enteroscopy (DBE) for
      obscure gastrointestinal bleeding. METHODS: From October 2003 to November 2009, a
      total of 124 patients with obscure gastrointestinal bleeding were investigated
      using DBE. A total of 142 procedures (84 per oral and 58 per rectal route) were
      performed by the same endoscopist. RESULTS: The average insertion time was 71.4
      (20-199) minutes per-orally; the average insertion time was 139.2 min for the
      first 5 procedures, 109.4 min for 6-10 procedures, 76.6 min for 11-15, 66.4 min
      for 16-20, 67.4 min for 21-25, 59 min for 26-30, 66 min for 31-35, 52 min for 36
      40, 42.9 min for 41-45, 44.6 min for 46-50, 42.2 min for 51-55, 38.6 min for 56
      60, 44.6 min for 61-65, 37.8 min for 66-70, 38.8 min for 71-75, 44.3 min for 76
      80, and 36.6 min for 61-84 procedures; there was no statistical difference after
      the first ten procedures. The average insertion time was 92.1 (22-260) minutes
      per-rectally; the average insertion time was 159.6 min for the first 5
      procedures, 98.4 min for 6-10 procedures, 86.6 min for 11-15, 76.4 min for 16-20,
      82.4 min for 21-25, 75.0 min for 26-30, 78.2 min for 31-35, 72.4 min for 36-40,
      68.2 min for 41-45, 66.9 min for 45-50, and 71.4 min for 51-58 procedures; there
      was no statistical difference after the first five procedures. For the different
      genders these was no statistically significant difference. There were no
      differences regarding the diagnostic yield between the previous factors. The
      overall diagnostic yield was 82.4%. CONCLUSION: DBE is a safe and effective means
      of diagnosing and managing patients with obscure gastrointestinal bleeding.
      However, because of its time-consuming, DBE has a learning curve to overcome
      before a physician can become an expert to achieve adequate insertion times with
      good diagnostic and therapeutic rates.

PMID- 29198552
TI  - Increased prevalence of proliferative retinopathy in patients with acromegaly.
AB  - BACKGROUND: This pilot study was carried to determine the prevalence of
      retinopathy, especially proliferative retinopathy, in patients with acromegaly.
      METHODS: We analyzed 43 acromegalic patients and 129 age- and gender-matched
      patients with type 2 diabetes. The retinopathy status was determined from the
      medical records based on the ophthalmologist consultations of patients with
      acromegaly. Color photographs of the macula- and disc-centered views were
      obtained at an angle of 45 degrees  with a fundus camera after pharmacologic
      induced mydriasis in patients with type 2 diabetes. RESULTS: Compared with age-
      and gender-matched patients with type 2 diabetes, the acromegalic patients had
      lower fasting plasma glucose levels and lower systolic and diastolic blood
      pressures, but were taller and had higher IGF-1 levels. Any degree of retinopathy
      was present in 9.3% (4 of 43) of patients with acromegaly and 34.9% (45 of 129)
      of patients with type 2 diabetes (odds ratio [OR] = 0.191; 95% confidence
      interval [CI] = 0.064-0.570). Proliferative retinopathy was present in 9.3% (4 of
      43) of patients with acromegaly and 9.3% (12 of 129) of patients with type 2
      diabetes (OR = 1.000; 95% CI = 0.305-3.281). Non-proliferative retinopathy was
      absent in patients with acromegaly, but present in 25.9% (33 of 129) of patients
      with type 2 diabetes. CONCLUSION: The high proliferative, but absence of non
      proliferative retinopathy in our patients with acromegaly may reflect the
      pathogenic effect of IGF-1 on neovascularization. IGF-1 may play an important
      role in proliferative retinopathy, but may play no role in non-proliferative
      retinopathy.

PMID- 29198553
TI  - 6-Month follow-up of a case with psychosis triggered by valacyclovir.

PMID- 29198555
TI  - Publish and perish.

PMID- 29198554
TI  - Research on rat's pulmonary acute injury induced by lunar soil simulant.
AB  - BACKGROUND: The steps to the moon never stopped after the Apollo Project. Lessons
      from manned landings on the moon have shown that lunar dust has great influence
      on the health of astronauts. In this paper, comparative studies between the lunar
      soil simulant (LSS) and PM2.5 were performed to discover their harm to human
      biological systems and explore the methods of prevention and treatment of dust
      poisoning for future lunar manned landings. METHODS: Rats were randomly divided
      into the control group, two CAS-1 lunar soil simulant groups (tracheal perfusion
      with 7 mg and 0.7 mg, respectively, in a 1-mL volume) and the PM2.5 group
      (tracheal perfusion with 0.7 mg in a 1-mL volume). The biochemical indicators in
      the bronchoalveolar lavage fluid (BALF), MPO activity in the lung tissue,
      pathologic changes, and inflammatory cells in the BALF were measured after 4 h
      and 24 h. RESULTS: The LSS group showed cytotoxicity that was closely related to
      the concentration. The figures of the two LSS groups (4 and 24 h) show that the
      alveolar septa were thickened. Additionally, it was observed that neutrophils had
      infiltrated, and various levels of inflammation occurred around the vascular and
      bronchial structures. CONCLUSION: The overall results of the acute effects of the
      lungs caused by dust showed that the lung toxicity of LSS was greater than that
      of PM2.5. LSS could induce lung damage and inflammatory lesions. The biomarkers
      in BALF caused by acute injury were consistent with histopathologic observations.

PMID- 29198556
TI  - Title ultrasound features of ovarian melanoma metastases: The "Golf ball" aspect.
AB  - Melanoma is an malignant tumor with an unpredictable profile of spread and
      variable periods of remissions. Both ovarian involvement of malignant melanoma
      and primary ovarian melanoma are extremely rare conditions with few cases
      reported in the literature. They always represent a diagnostic challenge as they
      mimic various ovarian entities from primary ovarian malignancy to benign tumors.
      Ovarian metastasis often present with images similar to the primary tumors, and
      there is no typical finding that differentiate them, apart from the multilocular
      tendency which would favor a primary process. We here report an extremely rare
      case of ovarian melanoma metastasis with detailed ultrasound examination, never
      specifically described in literature and whit the "Golf Ball" aspect. This
      metastatic tumor seems to be bilateral, with mean diameter (<10cm), main solid
      appearance, and rich vascularization, so more comparable to stomach-breast
      metastases. Moreover atypical multiple small cysts responsible of ultrasound
      "golf ball" aspect correspond to the histological diagnosis of follicular cysts
      surrounded by metastatic cancer while partial hyperechoic solid component could
      be related to the different histological pattern. These sonographic features may
      be useful in the difficult differential diagnosis between ovarian cancer
      primitive and ovarian melanoma metastases especially in cases with unclear
      patient history.

PMID- 29198557
TI  - Saffron: From Greek mythology to contemporary anti-atherosclerotic medicine.

PMID- 29198559
TI  - Department of Error.

PMID- 29198558
TI  - A new vision for global health leadership.

PMID- 29198560
TI  - Lipoamide Inhibits NF1 Deficiency-induced Epithelial-Mesenchymal Transition in
      Murine Schwann Cells.
AB  - BACKGROUND AND AIMS: Neurofibromatosis type I (NF1) is one of the most common
      neurocutaneous syndromes characterized by development of adult neurofibromas
      which is mainly made up of Schwann cells. The disease is generally accepted to be
      caused by inactivation mutation of Nf1 gene. And Nf1 deficiency had been reported
      to lead to ROS overproduction and epithelial-mesenchymal transition (EMT)
      phenotype. This study was designed to investigate whether excessive ROS conferred
      to Nf1 deficiency-induced EMT in Schwann cells. METHODS: Colony formation, wound
      healing assay and transwell assay was used to evaluate the effects of stable Nf1
      knockdown in SW10 Schwann cells. Western blot and ROS assay was conducted to
      explore the molecular mechanisms of Nf1 inactivation in tumorigenesis. Animal
      experiments were performed to assess the inhibitory effects of lipoamide, which
      is the neutral amide of alpha-lipoic acid and functions as a potent antioxidant
      to scavenge ROS, on Nf1-deficiency tumor growth in vivo. RESULTS: Nf1 knockdown
      enhanced the cellular capacities of proliferation, migration and invasion,
      promoted ROS generation, decreased the expression of epithelial surface marker E
      cadherin, and up-regulated several EMT-associated molecules in Schwann cells.
      Moreover, lipoamide dose-dependently inhibited not only Nf1 deficiency-induced
      EMT but also spontaneous EMT. Furthermore, lipoamide markedly suppresses tumor
      growth in a mouse model of NF1-associated neurofibroma. CONCLUSIONS: Our results
      clearly reveal that ROS overproduction is responsible for Nf1 deficiency-induced
      EMT and plays a crucial role in NF1 tumor growth. The findings presented herein
      shed light on the potential of antioxidant therapy to prevent the progression of
      NF1-associated neurofibroma.

PMID- 29198562
TI  - Disease burden and costs from excess alcohol consumption, obesity, and viral
      hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in
      the UK.
AB  - This report contains new and follow-up metric data relating to the eight main
      recommendations of the Lancet Standing Commission on Liver Disease in the UK,
      which aim to reduce the unacceptable harmful consequences of excess alcohol
      consumption, obesity, and viral hepatitis. For alcohol, we provide data on
      alcohol dependence, damage to families, and the documented increase in alcohol
      consumption since removal of the above-inflation alcohol duty escalator.
      Alcoholic liver disease will shortly overtake ischaemic heart disease with regard
      to years of working life lost. The rising prevalence of overweight and obesity,
      affecting more than 60% of adults in the UK, is leading to an increasing liver
      disease burden. Favourable responses by industry to the UK Government's soft
      drinks industry levy have been seen, but the government cannot continue to ignore
      the number of adults being affected by diabetes, hypertension, and liver disease.
      New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus
      infection have reduced mortality and the number of patients requiring liver
      transplantation, but more screening campaigns are needed for identification of
      infected people in high-risk migrant communities, prisons, and addiction centres.
      Provision of care continues to be worst in regions with the greatest
      socioeconomic deprivation, and deficiencies exist in training programmes in
      hepatology for specialist registrars. Firm guidance is needed for primary care on
      the use of liver blood tests in detection of early disease and the need for
      specialist referral. This report also brings together all the evidence on costs
      to the National Health Service and wider society, in addition to the loss of tax
      revenue, with alcohol misuse in England and Wales costing L21 billion a year
      (possibly up to L52 billion) and obesity costing L27 billion a year (treasury
      estimates are as high as L46 billion). Voluntary restraints by the food and
      drinks industry have had little effect on disease burden, and concerted
      regulatory and fiscal action by the UK Government is essential if the scale of
      the medical problem, with an estimated 63 000 preventable deaths over the next 5
      years, is to be addressed.

PMID- 29198561
TI  - Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational
      Regulation.
AB  - Covalent nucleotide modifications in noncoding RNAs affect a plethora of
      biological processes, and new functions continue to be discovered even for well
      known modifying enzymes. To systematically compare the functions of a large set
      of noncoding RNA modifications in gene regulation, we carried out ribosome
      profiling in budding yeast to characterize 57 nonessential genes involved in tRNA
      modification. Deletion mutants exhibited a range of translational phenotypes,
      with enzymes known to modify anticodons, or non-tRNA substrates such as rRNA,
      exhibiting the most dramatic translational perturbations. Our data build on prior
      reports documenting translational upregulation of the nutrient-responsive
      transcription factor Gcn4 in response to numerous tRNA perturbations, and
      identify many additional translationally regulated mRNAs throughout the yeast
      genome. Our data also uncover unexpected roles for tRNA-modifying enzymes in
      regulation of TY retroelements, and in rRNA 2'-O-methylation. This dataset should
      provide a rich resource for discovery of additional links between tRNA
      modifications and gene regulation.

PMID- 29198564
TI  - Linking stem cell function and growth pattern of intestinal organoids.
AB  - Intestinal stem cells (ISCs) require well-defined signals from their environment
      in order to carry out their specific functions. Most of these signals are
      provided by neighboring cells that form a stem cell niche, whose shape and
      cellular composition self-organize. Major features of this self-organization can
      be studied in ISC-derived organoid culture. In this system, manipulation of
      essential pathways of stem cell maintenance and differentiation results in well
      described growth phenotypes. We here provide an individual cell-based model of
      intestinal organoids that enables a mechanistic explanation of the observed
      growth phenotypes. In simulation studies of the 3D structure of expanding
      organoids, we investigate interdependences between Wnt- and Notch-signaling which
      control the shape of the stem cell niche and, thus, the growth pattern of the
      organoids. Similar to in vitro experiments, changes of pathway activities alter
      the cellular composition of the organoids and, thereby, affect their shape.
      Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern;
      known to occur spontaneously during long term organoid expansion. Based on our
      simulation results, we predict that the cyst-like pattern is associated with
      biomechanical changes of the cells which assign them a growth advantage. The
      results suggest ongoing stem cell adaptation to in vitro conditions during long
      term expansion by stabilizing Wnt-activity. Our study exemplifies the potential
      of individual cell-based modeling in unraveling links between molecular stem cell
      regulation and 3D growth of tissues. This kind of modeling combines experimental
      results in the fields of stem cell biology and cell biomechanics constituting a
      prerequisite for a better understanding of tissue regeneration as well as
      developmental processes.

PMID- 29198563
TI  - Transient transcriptional silencing alters the cell cycle to promote germline
      stem cell differentiation in Drosophila.
AB  - Transcriptional silencing is a conserved process used by embryonic germ cells to
      repress somatic fate and maintain totipotency and immortality. In Drosophila,
      this transcriptional silencing is mediated by polar granule component (pgc).
      Here, we show that in the adult ovary, pgc is required for timely germline stem
      cell (GSC) differentiation. Pgc is expressed transiently in the immediate GSC
      daughter (pre-cystoblast), where it mediates a pulse of transcriptional
      silencing. This transcriptional silencing mediated by pgc indirectly promotes the
      accumulation of Cyclin B (CycB) and cell cycle progression into late-G2 phase,
      when the differentiation factor bag of marbles (bam) is expressed. Pgc mediated
      accumulation of CycB is also required for heterochromatin deposition, which
      protects the germ line genome against selfish DNA elements. Our results suggest
      that transient transcriptional silencing in the pre-cystoblast "re-programs" it
      away from self-renewal and toward the gamete differentiation program.

PMID- 29198565
TI  - EvoRegen in animals: Time to uncover deep conservation or convergence of adult
      stem cell evolution and regenerative processes.
AB  - How do animals regenerate specialised tissues or their entire body after a
      traumatic injury, how has this ability evolved and what are the genetic and
      cellular components underpinning this remarkable feat? While some progress has
      been made in understanding mechanisms, relatively little is known about the
      evolution of regenerative ability. Which elements of regeneration are due to
      lineage specific evolutionary novelties or have deeply conserved roots within the
      Metazoa remains an open question. The renaissance in regeneration research,
      fuelled by the development of modern functional and comparative genomics, now
      enable us to gain a detailed understanding of both the mechanisms and
      evolutionary forces underpinning regeneration in diverse animal phyla. Here we
      review existing and emerging model systems, with the focus on invertebrates, for
      studying regeneration. We summarize findings across these taxa that tell us
      something about the evolution of adult stem cell types that fuel regeneration and
      the growing evidence that many highly regenerative animals harbor adult stem
      cells with a gene expression profile that overlaps with germline stem cells. We
      propose a framework in which regenerative ability broadly evolves through changes
      in the extent to which stem cells generated through embryogenesis are maintained
      into the adult life history.

PMID- 29198566
TI  - Pseudotyped baculovirus is an effective gene expression tool for studying
      molecular function during axolotl limb regeneration.
AB  - Axolotls can regenerate complex structures through recruitment and remodeling of
      cells within mature tissues. Accessing the underlying mechanisms at a molecular
      resolution is crucial to understand how injury triggers regeneration and how it
      proceeds. However, gene transformation in adult tissues can be challenging. Here
      we characterize the use of pseudotyped baculovirus (BV) as an effective gene
      transfer method both for cells within mature limb tissue and within the blastema.
      These cells remain competent to participate in regeneration after transduction.
      We further characterize the effectiveness of BV for gene overexpression studies
      by overexpressing Shh in the blastema, which yields a high penetrance of classic
      polydactyly phenotypes. Overall, our work establishes BV as a powerful tool to
      access gene function in axolotl limb regeneration.

PMID- 29198568
TI  - NosP-Regulated Nosiheptide Production Responds to Both Peptidyl and Small
      Molecule Ligands Derived from the Precursor Peptide.
AB  - Nosiheptide, an archetypal member of thiopeptide antibiotics, arises from post
      translational modifications of a ribosomally synthesized precursor peptide that
      contains an N-terminal leader peptide (LP) sequence and a C-terminal core peptide
      (CP) sequence. Despite extensive efforts concerning the biosynthesis of
      thiopeptide antibiotics, the regulatory mechanisms in this process remain poorly
      understood. Using the nosiheptide-producing Streptomyces actuosus strain as a
      model system, we report here that NosP, a Streptomyces antibiotic regulatory
      protein, serves as the only cluster-situated regulator and activates the
      transcription of all structural genes, which are organized into two divergently
      transcribed operons in the nos cluster, by binding to their intergenic region.
      NocP, the counterpart of NosP in Nocardia sp., regulates the production of
      structurally related nocathiacin I in a similar manner. NosP activity senses the
      nosiheptide biosynthetic process by interactions with both peptidyl and small
      molecule ligands that result from the LP and CP parts of the precursor peptide,
      respectively.

PMID- 29198567
TI  - Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the
      Ancient Kinase-like UbiB Family.
AB  - Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are
      UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis.
      However, the biochemical activity of COQ8 and its direct role in CoQ production
      remain unclear, in part due to lack of known endogenous regulators of COQ8
      function and of effective small molecules for probing its activity in vivo. Here,
      we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that
      is activated by binding to membranes containing cardiolipin and by phenolic
      compounds that resemble CoQ pathway intermediates. We further create an analog
      sensitive version of Coq8p and reveal that acute chemical inhibition of its
      endogenous activity in yeast is sufficient to cause respiratory deficiency
      concomitant with CoQ depletion. Collectively, this work defines lipid and small
      molecule modulators of an ancient family of atypical kinase-like proteins and
      establishes a chemical genetic system for further exploring the mechanistic role
      of COQ8 in CoQ biosynthesis.

PMID- 29198569
TI  - A combination of clinical risk stratification and fecal immunochemical test is
      useful for identifying persons with high priority of early colonoscopy.
AB  - BACKGROUND: We aimed to develop a combination screening strategy for advanced
      colorectal neoplasia based on the Asia-Pacific Colorectal Screening score and
      fecal immunochemical test results. METHODS: We reviewed the records of
      participants who had undergone a colonoscopy and fecal immunochemical test as
      part of a comprehensive health screening program. The prevalence of advanced
      colorectal neoplasia in participants 40-49 years old was analyzed according to
      Asia-Pacific Colorectal Screening scores and fecal immunochemical test results.
      RESULTS: We analyzed the data of 9205 participants 40-49 years old and 3215
      participants >=50 years old. The prevalence of advanced colorectal neoplasia in
      participants 40-49 years old was 1.0%, 2.1%, 7.1%, and 13.4% in the "fecal
      immunochemical test (-) & Asia-Pacific Colorectal Screening<2," "fecal
      immunochemical test (-) & Asia-Pacific Colorectal Screening>=2," "fecal
      immunochemical test (+) & Asia-Pacific Colorectal Screening<2," and "fecal
      immunochemical test (+) & Asia-Pacific Colorectal Screening>=2" subgroups,
      respectively. The prevalence of advanced colorectal neoplasia in "fecal
      immunochemical test (+) & Asia-Pacific Colorectal Screening>=2" subgroup was
      higher than in participants >=50 years old with Asia-Pacific Colorectal
      Screening>=4 (13.4% vs. 5.8%, P<0.001). CONCLUSIONS: Fecal immunochemical test
      positive individuals 40-49 years old with an Asia-Pacific Colorectal Screening>=2
      have a higher risk of advanced colorectal neoplasia than individuals >=50 years
      old with an Asia-Pacific Colorectal Screening>=4.

PMID- 29198570
TI  - Every polyp is not an adenoma: Ganglioneuroma of the colon.

PMID- 29198571
TI  - Wearing long sleeves while prepping a patient in the operating room decreases
      airborne contaminants.
AB  - BACKGROUND: The use of long sleeves by nonscrubbed personnel in the operating
      room has been called into question. We hypothesized that wearing long sleeves and
      gloves, compared with having bare arms without gloves, while applying the skin
      preparation solution would decrease particulate and microbial contamination.
      METHODS: A mock patient skin prep was performed in 3 different operating rooms. A
      long-sleeved gown and gloves, or bare arms, were used to perform the procedure.
      Particle counters were used to assess airborne particulate contamination, and
      active and passive microbial assessment was achieved through air samplers and
      settle plate analysis. Data were compared with Student's t-test or Mann-Whitney
      U, and P < .05 was considered to be significant. RESULTS: Operating room B
      demonstrated decreased 5.0- um particle sizes with the use of sleeves, while
      operating rooms A and C showed decreased total microbes only with the use of
      sleeves. Despite there being no difference in the average number of total
      microbes for all operating rooms assessed, the use of sleeves specifically
      appeared to decrease the shed of Micrococcus. CONCLUSION: The use of long sleeves
      and gloves while applying the skin preparation solution decreased particulate and
      microbial shedding in several of the operating rooms tested. Although long
      sleeves may not be necessary for all operating room personnel, they may decrease
      airborne contamination while the skin prep is applied, which may lead to
      decreased surgical site infections.

PMID- 29198573
TI  - The promoter polymorphisms in HTR2A gene associated with schizophrenia in Chinese
      of Han ethnicity.

PMID- 29198572
TI  - Acute Myocardial Infarction as the Initial Manifestation of Delayed Bioprosthesis
      Thrombosis After Transcatheter Aortic Valve Replacement.
AB  - Bioprosthesis thrombosis after transcatheter aortic valve replacement (TAVR)
      raised concerns about further clinical events. We report the case of a patient
      who suffered acute myocardial infarction (AMI) after TAVR for 3 years. Thrombosis
      was confirmed in the right coronary sinus of Valsalva by transthoracic
      echocardiography. Coronary angiography demonstrated the ostium of the right
      coronary artery was occluded. As an attempt to perform percutaneous coronary
      intervention (PCI) was unsuccessful, long-term therapeutic anticoagulation with
      warfarin was undertaken. Within 2 weeks, symptoms were relieved, and the right
      coronary ostium thrombus disappeared on computed tomography (CT) angiography.
      This case highlights the AMI as initial manifestation of delayed bioprosthesis
      thrombosis and the importance of anticoagulation against the bioprosthesis
      thrombosis. Meanwhile, the difficulty of PCI after TAVR is not only the stent
      frame of bioprosthesis, but also the location of the thrombosis.

PMID- 29198574
TI  - Design and application of a fluorogenic assay for monitoring inflammatory caspase
      activity.
AB  - Various fluorogenic assays exist for monitoring the activity of inflammatory
      caspases. However, there are no continuous assays that provide C-terminal
      substrate sequence specificity for inflammatory caspases. As a first step towards
      this, we have developed a continuous in vitro assay that relies on monitoring
      emission from tryptophan after cleavage of a quenching coumarin chromophore. The
      coumarin can be attached as an amino acid side chain or capping the C-terminus of
      the peptide. When the coumarin is a side chain, it allows for C-terminal and N
      terminal sequence specificities to be explored. Using this assay, we obtained
      Michaelis-Menten kinetic data for four proof-of-principle peptides: WEHD-AMC (KM
      = 15 +/- 2 MUM), WEHD-MCA (KM = 93 +/- 19 MUM), WEHDG-MCA (KM = 21 +/- 6 MUM) and
      WEHDA-MCA (KM = 151 +/- 37 MUM), where AMC is 7-amino-4-methylcoumarin and MCA is
      beta-(7-methoxy-coumarin-4-yl)-Ala. The results indicate the viability of this
      new assay approach in the design of effective fluorogenic substrates for
      inflammatory caspases.

PMID- 29198575
TI  - Voltammetric determination of thujone in herbal matrices in the presence of
      Triton X-100.
AB  - A simple, sensitive and rapid method of low concentration of thujone
      determination using Controlled Growth Mercury Drop Electrode and Differential
      Pulse Voltammetry was described. The reduction of thujone in phosphoric acid or
      potassium nitrate, involves a quasi-reversible and adsorption-controlled two
      electron process. In voltammetric experiments the addition of ethanol and Triton
      X-100 is recommended. Experimental conditions, such as composition of supporting
      electrolyte, concentration of Triton X-100 and operation parameters were
      established. The optimal electrolyte should contain: 0.04 mol L-1 phosphoric acid
      (pH = 1.9) or 0.05 mol L-1 potassium nitrate (pH = 6.4), 0.0002% Triton X-100 and
      9.6% ethanol. The calibration graph was linear from 0.7 to 140 mgL-1 of thujone
      in H3PO4 as supporting electrolyte and from 0.7 to 115 mgL-1 of the analyte in
      KNO3. The detection limit was 0.4 mgL-1 in H3PO4 and 0.6 mgL-1 in KNO3, with the
      correlation coefficient of 0.998. The influence of interfering substances, such
      as Al(III), Bi(III), Cd(II), Cr(III), Cu(II), Pb(II), Tl(I), V(III) and Zn(II)
      was studied. The proposed method was validated by the thujone recovery study from
      the specially prepared spiked herbal matrices and alcohol extract. The considered
      real sample was thuja oil, in which thujone was successfully determined. All
      measurements were performed without sample preparation.

PMID- 29198576
TI  - Influencing factors of domestic waste characteristics in rural areas of
      developing countries.
AB  - Waste management in rural areas has become a major challenge for governments of
      developing countries. The success of waste management decisions directly lies in
      the accuracy and reliability of the data on which choices are based; many factors
      influence these data. Here, we examined the factors influencing domestic waste in
      rural areas of developing countries (RADIC), using both field surveys and by
      reviewing previous literature. The social factors included population, education
      and culture. There was a positive linear relationship between waste generation
      amount and population size (R2 = 0.9405). Environmental education, training and
      demonstration projects played a positive role in improving people's awareness of
      the benefits of recycling and reducing waste. Traditional and national cultures,
      consumption and living habits contributed to variations in the generation and
      composition of domestic waste. Generally, practices related to conservation of
      and reverence for nature and green consumption encourage people to reduce, reuse
      and recycle waste in their daily life. Economic factors included household income
      and expenditure, energy and fuel structure, and types of industry that occurred
      in villages. A Kuznets inverted "U" curve relationship existed between domestic
      waste generation and people's income in rural areas of China. However, the waste
      generation rate had a linear relationship with the gross national income per
      capita in RADIC. The composition, bulk density and calorific value of domestic
      waste were variously affected by the energy and fuel structure and the types of
      industry that occurred. The natural factors included geography and climate
      (including rainfall, humidity, temperature and harvest seasons). The moisture
      content of waste was directly influenced by rainfall and humidity. Temperature
      affected waste characteristics by influencing residential heating modes. The
      waste characteristics were also influenced by the mixing of agricultural and
      aquacultural waste into domestic waste in the harvesting season. In different
      geographies, significant differences of domestic waste characteristics were
      observed as a result of comprehensive effects caused by multiple factors. Other
      factors included the administrative levels of communities and survey methods. The
      characteristics of domestic waste in towns or central villages were similar with
      those in cities, but were different from those in common villages (the smallest
      type of community). The domestic waste sampled in households indicated a lower
      rate of generation and lower ash content than when the waste was sampled at
      transfer stations or dumping sites. Based on the above analysis, the factors
      influencing domestic waste must be considered in order to optimize the design of
      waste management strategies in the RADIC. Furthermore, it is valuable and
      important to obtain more accurate data about waste characteristics.

PMID- 29198577
TI  - Bone autografts & allografts placed simultaneously with dental implants in
      rabbits.
AB  - OBJECTIVE: This study compared stability, removal torque, bone implant contact
      (BIC) and area (BA) of implants installed simultaneously with onlay autografts or
      allografts in rabbits' tibias. MATERIAL AND METHODS: Total of 18 rabbits were
      used in this study. Fresh frozen allografts were obtained from six animals at T(
      6). Two implants with autogenous grafts (Group 1) or allografts (Group 2) were
      simultaneously inserted into both sides of the tibiae in a vertical periimplant
      defect model at T0. The resonance frequency (ISQ) was measured in implant
      proximal epiphysis on the day of installation of T0 and T18 (18 weeks post
      surgery). At T18 the removal torque was assessed at the distal implants, the
      implants' proximal epiphysis and surrounding bone were harvested to perform
      histomorphometric analysis. The BIC and BA within the limits of the implants
      threads were evaluated. RESULTS: The ISQ revealed a statistically significant
      difference between T0 and T18 in each group (p = 0.024, p = 0.003). The removal
      torque indicates that there was no significant difference between the two groups
      (p = 0.47). No significant differences were observed between the groups regarding
      both BIC (p = 0.3713) and the BA (p = 0.3883). CONCLUSION: Both grafts and
      implants demonstrated the same stability, torque removal and the BIC and BA.

PMID- 29198578
TI  - Influence of gender on epithelial host defence peptide gene expression under non
      infected and infected conditions: A basic medical research study.
AB  - Bacterial resistance against conventional antibiotics is increasing. This
      introduces challenges, for example, in the treatment of infected surgical wounds.
      Host defence peptides (HDP), which are endogenous peptide antibiotics, show broad
      spectrum antimicrobial effectiveness. They protect the organism against
      pathological microorganisms. Synthetic HDP might supplement or even become
      alternatives to conventional antibiotics. Knowledge of their quantities under
      physiological and pathophysiological conditions is therefore required. The
      influence of gender on HDP expression is unknown. This study evaluates whether
      gender influences HDP expression in infected or healthy epithelium. Expression
      levels of HDP human beta-defensin (hBD)-1, -2 and -3 and psoriasin (S100A7) were
      analysed, by using real-time polymerase chain reaction, in samples of epithelium
      from infected surgical wounds (n = 20) and healthy epithelium (n = 14) from the
      neck in a basic medical research study (analytic observational design). The
      results demonstrated a significantly elevated expression of hBD-2, hBD-3 and
      psoriasin (P = 0.001 each) in infected epithelium compared with healthy
      epithelium. No difference in HDP expression levels was evident between samples
      from female and male patients, either within infected samples or within healthy
      epithelium samples. Thus, gender does not affect the cutaneous expression of the
      investigated HDP. This is fundamental knowledge for the study and potential use
      of HDP derivates as alternative antibiotic substances.

PMID- 29198579
TI  - Determination of VEGF, collagen type 1 and versican in the discus articularis of
      the temporomandibular joint in relation to dental status.
AB  - The aim of this study was the investigation and comparison of the presence of
      vascular endothelial growth factor (VEGF), collagen type 1 and the proteoglycan
      versican in the discus articularis in relation to dental status (full dentition
      [1], partial dentition [2] and edentulous [3]). The right disci articulares were
      removed from 17 donated bodies (6 with full dentition, 5 with partial dentition
      and 6 edentulous). The specimens were immunohistochemically stained for VEGF,
      collagen type 1 and versican. Semiquantitative analysis of the disci was
      conducted within the groups based on the intensity of immunoreactivity of VEGF,
      collagen type 1 and versican. In addition, a pairwise comparison was carried out
      between the three experimental groups. The results revealed significantly higher
      immunoreactivity for VEGF and versican in groups 2 and 3 than in group 1.
      Conversely, determination of immunoreactivity was significantly higher in group 1
      for collagen type 1 than in the other two groups. These results indicate an
      elevated presence of the proteoglycan versican and the neoangiogenesis factor
      VEGF when the occlusal supporting zone has been lost. By contrast, detection of
      collagen type 1 is reduced. The loss of collagen type 1 and rise in versican and
      VEGF suggest increasing degeneration when the supporting zone is lost due to the
      loss of teeth.

PMID- 29198580
TI  - Autoimmune hypoglycemia due to anti-insulin antibodies.

PMID- 29198581
TI  - A case of incoercible pruritus.

PMID- 29198582
TI  - Invasive disease due to Neisseria meningitidis serogroup W.

PMID- 29198583
TI  - Substitution Urethroplasty with Closure Versus Nonclosure of the Buccal Mucosa
      Graft Harvest Site: A Randomized Controlled Trial with a Detailed Analysis of
      Oral Pain and Morbidity.
AB  - BACKGROUND: Optimal surgical management of the buccal mucosa harvest site in
      patients with urethral stricture disease during buccal mucosa graft urethroplasty
      (BMGU) remains controversial. OBJECTIVE: To analyze in detail intensity and
      quality of pain as well as oral morbidity following closure (C) versus nonclosure
      (NC) of the donor site. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled
      trial on 135 patients treated with BMGU between October 15, 2014 and December 18,
      2015. INTERVENTION: Following computer-based randomization, 63 and 72 patients,
      respectively, received C and NC of the donor site at the inner cheek.
      Preoperatively, on days 1, 5, and 21 as well as at 3 and 6 mo postoperatively,
      patients completed standardized questionnaires, including validated questions on
      intensity and quality of pain as well as oral morbidity. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The coprimary end points were intensity and quality of oral
      pain. Secondary end points included oral morbidity and intensity of pain of the
      perineogenital region. Generalized linear mixed models evaluated the effect of
      various covariates on intensity and quality of oral pain, oral morbidity, as well
      as intensity of pain of the perineogenital region. RESULTS AND LIMITATIONS: There
      was noninferiority for NC versus C in intensity and affective quality of oral
      pain at every time point following BMGU. Oral morbidity and complications
      included pain, bleeding, swelling, numbness, alteration of salivation and taste,
      as well as impairment of mouth opening, smiling, whistling, diet, and speech.
      Time from BMGU had significant effects on intensity (p<0.001) and quality of oral
      pain (sensory pain: p<0.001, affective pain: p<0.001, total pain: p<0.001).
      Length of buccal mucosa graft had significant effects on intensity (p=0.001) and
      quality of oral pain (sensory pain: p=0.020, total pain: p=0.042). CONCLUSIONS:
      NC is noninferior to C of the donor site in intensity and quality of oral pain,
      and offers a treatment alternative. Time from BMGU and length of the buccal
      mucosa graft have effects on oral morbidity and complications. PATIENT SUMMARY:
      We investigated pain, morbidity, and complications following closure (C) versus
      nonclosure (NC) of the buccal mucosa harvest site in patients undergoing buccal
      mucosa graft urethroplasty (BMGU). We found that NC is not worse than C regarding
      oral pain. In addition, time from BMGU and length of the buccal mucosa graft have
      effects on oral morbidity and complications.

PMID- 29198584
TI  - Aptamers targeting cell surface proteins.
AB  - High affinity binders targeting specific cell surface proteins are vital for
      development of basic and applied biosciences. However, despite sustained efforts
      to generate such binders by chemicals and antibodies, there are still many cell
      surface proteins that lack high affinity binders. Nucleic acid aptamers have
      potential as binding molecules for cell surface proteins, because they form
      distinct structures that have high affinity and specificity for a wide range of
      targets. Aptamers are isolated from large combinatorial libraries using a unique
      iterative selection-amplification process known as systematic evolution of
      ligands by exponential enrichment (SELEX). Among advantages of this method,
      purified and complex heterogeneous targets, such as bacteria, viruses, and whole
      living cells, can be used for selection of aptamers. Moreover, SELEX allows
      generation of cell-surface-specific aptamers without prior knowledge of
      expression profiles in target cells. Therefore, the technology has been widely
      used as a valid and feasible method to generate aptamers binding to cell surface
      proteins with intact structure. Herein, this review summarizes and updates iconic
      SELEX technologies that target membrane proteins.

PMID- 29198585
TI  - A multidisciplinary approach for the management of earlier stage renal cell
      carcinoma.
AB  - Transitioning agents that are effective in advanced disease to earlier disease
      settings is a common pathway for drug development and a concept that has been
      applied to multiple agents across several tumor types. This approach is relevant
      in high risk renal cell carcinoma (RCC) where the relapse rate is high.
      Unfortunately, between 20% and 40% relapse after nephrectomy and approximately
      one third of patients have evidence of metastasis at initial diagnosis. These
      patients will proceed with focal or systemic therapy during the course of
      disease.

PMID- 29198586
TI  - Metastases of malignant neoplasms: Historical, biological, & clinical
      considerations.
AB  - The metastasis of neoplastic cells from their site of origin to distant anatomic
      locations continues to be the principal cause of death from malignant tumors, and
      that fact has been recognized by physicians for over a century. After the work
      done by Halsted in the treatment of breast cancer in the 1880s, accepted surgical
      canon held that metastasis occurred in a linear fashion, with centrifugal "growth
      in continuity" from the primary neoplasm that first involved regional lymph
      nodes. Those structures were considered to then be the sources of more distant,
      visceral metastases. With that premise in mind, radical and "ultra-radical"
      surgical procedures were devised to remove as many lymph nodes as possible in the
      treatment of carcinomas and melanomas. However, such interventions were
      ineffective in altering tumor-related mortality. This review considers the
      details of the historical material just mentioned. It also reviews currently-held
      concepts on biological mechanisms of metastasis, the "sentinel" lymph node biopsy
      technique, and the important topic of metastatic tumor "dormancy" as the cause of
      surgical treatment failure. Finally, predictive models of tumor behavior are
      discussed, which are based on gene signatures. These will likely be the key to
      identifying malignant lesions of low surgical stage that ultimately prove fatal
      through later manifestation of metastasis.

PMID- 29198587
TI  - Bedroom allergen exposures in US households.
AB  - BACKGROUND: Bedroom allergen exposures contribute to allergic disease morbidity
      because people spend considerable time in bedrooms, where they come into close
      contact with allergen reservoirs. OBJECTIVE: We investigated participant and
      housing characteristics, including sociodemographic, regional, and climatic
      factors, associated with bedroom allergen exposures in a nationally
      representative sample of the US population. METHODS: Data were obtained from
      National Health and Nutrition Examination Survey 2005-2006. Information on
      participant and housing characteristics was collected by using questionnaires and
      environmental assessments. Concentrations of 8 indoor allergens (Alt a 1, Bla g
      1, Can f 1, Fel d 1, Der f 1, Der p 1, Mus m 1, and Rat n 1) in dust vacuumed
      from nearly 7000 bedrooms were measured by using immunoassays. Exposure levels
      were classified as increased based on percentile (75th/90th) cutoffs. We
      estimated the burden of exposure to multiple allergens and used multivariable
      logistic regression to identify independent predictors for each allergen and
      household allergen burden. RESULTS: Almost all participants (>99%) had at least 1
      and 74.2% had 3 to 6 allergens detected. More than two thirds of participants
      (72.9%) had at least 1 allergen and 18.2% had 3 or more allergens exceeding
      increased levels. Although exposure variability showed significant racial/ethnic
      and regional differences, high exposure burden to multiple allergens was most
      consistently associated with the presence of pets and pests, living in mobile
      homes/trailers and older and rental homes, and living in nonmetropolitan areas.
      CONCLUSIONS: Exposure to multiple allergens is common. Despite highly variable
      exposures, bedroom allergen burden is strongly associated with the presence of
      pets and pests.

PMID- 29198588
TI  - How much is enough-Can resting state fMRI provide a demarcation for neurosurgical
      resection in glioma?
AB  - This study represents a systematic review of the insights provided by resting
      state functional MRI (rs-fMRI) use in the glioma population. Following PRISMA
      guidelines, 45 studies were included in the review and were classified in glioma
      related neuronal changes (n=28) and eloquent area localization (n=17). Despite
      the heterogeneous nature of the studies, there is considerable evidence of
      diffuse functional reorganization occurring in the setting of gliomas with local
      and interhemispheric functional connectivity alterations involving different
      functional networks. The studies showed evidence of decreased long distance
      functional connectivity and increased global local efficiency occurring in the
      setting of gliomas. The tumour grade seems to correlate with distinct functional
      connectivity changes. Overall, there is a potential clinical utility of rs-fMRI
      for identifying the functional brain network disruptions occurring in the setting
      of gliomas. Further studies utilizing standardized analytical methods are
      required to elucidate the mechanism through which gliomas induce global changes
      in brain connectivity.

PMID- 29198590
TI  - Clinical Outcomes of Single Anteromedial Bundle Biologic Augmentation Technique
      for Anterior Cruciate Ligament Reconstruction With Consideration of Tibial
      Remnant Size.
AB  - PURPOSE: The primary aim of this study was to evaluate the functional outcomes,
      knee stability, complications, and reoperations associated with anatomic anterior
      cruciate ligament (ACL) reconstruction using the single anteromedial bundle
      biological augmentation (SAMBBA) technique in a consecutive series of 128
      patients with a minimum follow-up of 24 months. A secondary aim was to compare
      larger preserved ACL remnants with smaller preserved remnants. METHODS: Patients
      who underwent primary anatomic ACL reconstruction using the SAMBBA technique from
      July 2013 to October 2014 were analyzed. Exclusion criteria were (1) age <16
      years, (2) revision cases, (3) multiple ligament injuries, (4) chondral lesions
      greater than grade 2 according to the Outerbridge classification, (5) additional
      injuries to the collateral ligaments greater than grade 2, or (6) a history of a
      contralateral ACL injury. Clinical assessment including evaluation of side-to
      side difference and functional outcome measures with the International Knee
      Documentation Committee (IKDC) subjective score and the Tegner Activity Scale
      were used to evaluate outcomes before surgery and at the last follow-up. Any
      subsequent surgical procedures were systematically recorded during the study
      period. The patients were also divided in 2 groups according to their ACL remnant
      size, >=50% or <50%, and compared. RESULTS: Of the 135 patients who underwent
      primary SAMBBA technique, 128 patients returned to final follow-up, with a mean
      follow-up of 31.7 months (range, 24-44.3). At last follow-up, the IKDC score
      significantly improved from 54.1 +/- 15.1 to 92.5 +/- 11.4 (P < .001); the Tegner
      activity score (6.4 +/- 1.2) was similar (P = .3) to the preinjury score (6.5 +/-
      1.2). Side-to-side laxity significantly improved from 6.7 +/- 1.2 mm to 0.7 +/- 1
      mm (P < .001). Twenty-four subsequent surgeries (18.7%) were performed including
      10 meniscal procedures, 7 ACL revisions, 5 arthroscopies for cyclops lesions, one
      microfracture, and one manipulation under anaesthesia. The side-to-side laxity (P
      = .30) and rates of reoperation (P = .65), graft failure (P = .45), and cyclops
      lesions (P = .67) were not significantly different between >=50% or <50% ACL
      remnant groups. CONCLUSIONS: The results of this study demonstrate that primary
      anatomic ACL reconstruction using the SAMBBA technique significantly improved
      clinical and functional outcomes between baseline and follow-up at a minimum of
      24 months. A low rate of complications was observed with this technique. No
      significant differences between large and moderate size ACL remnants were
      detected for all outcome measures. LEVEL OF EVIDENCE: Level IV case series with
      subgroup analysis.

PMID- 29198589
TI  - [Environment and lifestyle: Impacts on male fertility?]
AB  - In this last century, an increase of men infertility has been registered. It has
      been suggested that environmental factors could a negative impact over sperm
      quality. Among these factors, impact of environmental toxicant has been spread by
      media. In this review of scientific literature, we identify several environmental
      factors that could impact men fertility in a negative way. These factors are
      tobacco, marijuana, weight, body mass index, heat, nutritional state,
      electromagnetic waves and altitude. For each of these factors, the impact over
      men fertility, their mechanism, as well their influence over the use of Assisted
      Reproductive Technics are reported.

PMID- 29198591
TI  - In vivo facial soft tissue thicknesses of adult Australians.
AB  - Facial soft tissue thicknesses (FSTT) set important quantitative guides in
      craniofacial identification, but so far Australian FSTTs have only been published
      for supine cadavers. This study aimed to use B-mode ultrasound to measure FSTTs
      in living Australians (N=63 participants; n1=52 [x-=21 years, s=2 years]; and
      n2=11 [x-=54years, s=13years]) using 14 craniometric landmarks with participants
      in both upright and supine positions. The multiple pre-existing Australian
      cadaver investigations (n=7 reporting FSTT means and 6 of these reporting raw
      datasets) enabled living and cadaveric samples drawn from the same parent
      population to be compared. By using a non-invasive and safe imaging method (no
      ionising radiation) repeated measurements could be taken in the in vivo
      participants to gauge measurement reliability (and compare to pre-existing
      reliability for cadaver measurements): mean r-TEM=12%; max r-TEM=25%. In terms of
      changes between upright and supine positions (as measured by B-mode ultrasound)
      only 2 of 14 measured landmarks had FSTT changes in excess of 1mm. Comparisons of
      the in vivo ultrasound data to pre-existing needle puncture studies demonstrated
      that mean B-mode ultrasound measurements were very similar to cadaver values.
      Contrary to popular thought, but in keeping with the findings of prior meta
      analyses, cadaver FSTT data are good proxies to living subjects, at least as
      measured by ultrasound. To increase sample sizes and triangulate upon ground
      truth FSTT values, weighted grand means combining all Australian samples were
      calculated (n range=280-385) and compared to the multi-group 2018 adult T-Tables
      (max. n=10,333).

PMID- 29198592
TI  - Can Tangier disease cause male infertility? A case report and an overview on
      genetic causes of male infertility and hormonal axis involved.
AB  - Tangier disease is an autosomal recessive disorder caused by mutations in the
      ABCA1 gene and characterized by the accumulation of cholesteryl ester in various
      tissues and a near absence of high-density lipoprotein. The subject in this
      investigation was a 36-year-old Italian man with Tangier disease. He and his wife
      had come to the In Vitro Fertilization Unit, Pesaro Hospital (Azienda Ospedaliera
      Ospedali Riuniti Marche Nord) seeking help regarding fertility issues. The man
      was diagnosed with severe oligoasthenoteratozoospermia. Testosterone is the sex
      hormone necessary for spermatogenesis and cholesterol is its precursor; hence, we
      hypothesized that the characteristic cholesterol deficiency in Tangier disease
      patients could compromise their fertility. The aim of the study was to therefore
      to determine if there is an association between Tangier disease and male
      infertility. After excluding viral, infectious, genetic and anatomical causes of
      the subject's oligoasthenoteratozoospermia, we performed a hormonal analysis to
      verify our hypothesis. The patient was found to be negative for frequent bacteria
      and viruses. The subject showed a normal male karyotype and tested negative for
      Yq microdeletions and Cystic Fibrosis Transmembrane Conductance Regulator gene
      mutations. A complete urological examination was performed, and primary
      hypogonadism was also excluded. Conversely, hormonal analyses showed that the
      subject had a high level of follicle stimulating hormone and luteinizing hormone,
      low total testosterone and a significant decline in inhibin B. We believe that
      the abnormally low cholesterol levels typically found in subjects with Tangier
      disease may result in a reduced testosterone production which in turn could
      affect the hormonal axis responsible for spermatogenesis leading to a defective
      maturation of spermatozoa.

PMID- 29198593
TI  - A new generation of cellulose triacetate suitable for online haemodiafiltration.
AB  - BACKGROUND: Online haemodiafiltration (OL-HDF) is currently the most effective
      dialysis technique that also improves survival. To date, high permeability
      membranes with low albumin loss, such as polysulfone, polyamide and
      polyacrylonitrile membranes have been the most widely used. However, the
      initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has
      expanded. The aim of the study was to ascertain whether the latest generation
      asymmetric CTA membranes are more effective in obtaining high convective
      transport. PATIENTS AND METHODS: A total of 16 patients (10 males and 6 females)
      undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with
      haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m2 membranes. Each
      session was assigned in a randomised order. Serum levels of urea, creatinine,
      beta2-microglobulin, myoglobin, prolactin, alpha1-microglobulin, alpha1-acid
      glycoprotein and albumin where measured at the beginning and end of each session
      to obtain the reduction rate. The loss of solutes and albumin was quantified from
      the dialysate. RESULTS: A significantly greater replacement volume in OL-HDF
      (32.1+/-3.1 vs. 19.7+/-4.5 l, P<.001) was obtained by using asymmetrical CTA
      membranes compared to conventional CTA membranes. Regarding uraemic toxin
      removal, both membranes obtained similar results for small molecules, whereas
      asymmetric CTA membranes achieved better results for large molecules, increasing
      the reduction ratio by 29% for beta2-microglobulin, 27.7% for myoglobin, 19.5%
      for prolactin, 49% for alpha1-microglobulin and double for alpha1-acid
      glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g
      for all treatment sessions. CONCLUSION: Latest-generation asymmetric CTA have
      proven to be effective in attaining OL-HDF objectives without increased albumin
      loss.

PMID- 29198594
TI  - Giardia duodenalis mouse model for the development of novel antigiardial agents.
AB  - This study describes a neonatal mouse model of Giardia infection for development
      of novel antigiardials. Mice were infected with the axenically cultured
      Assemblage A BAH2c2 strain, with 105 trophozoites per animal recovered. This
      model proved to be robust and consistent for use in preliminary drug efficacy
      trials and drug development.

PMID- 29198595
TI  - [Influence of the professional experience of the clinical cardiologist on the
      adequacy of the clinical indications of myocardial perfusion gated-SPECT].
AB  - OBJECTIVE: During cardiology training, the cardiology fellow has to be trained in
      all things related to the indication, interpretation, and performing of nuclear
      cardiology studies using single photon emission computed tomography (SPECT). The
      aim of the present study was to analyse the relationship between the adequacy of
      indications of myocardial perfusion gated-SPECT and the years of experience since
      the completion of cardiology training. METHOD: A descriptive, retrospective
      analysis was performed on a single-centre register, in which the indications
      (adequate or inadequate use) were recorded according to myocardial perfusion
      gated-SPECT guidelines, prescribed by cardiologists of a university hospital.
      RESULTS: A total of 950 gated-SPECT tests were analysed according to the
      appropriate or inadequate indication. The sample of study was distributed in
      quartiles (years) since the cardiologist finished the residency. Cardiologists
      with less than 10 years of clinical experience reported a higher proportion of
      gated-SPECT tests compared to the more experienced cardiologists (87.6 vs. 9.3%,
      P<.001). After adjusting for age, gender, and cardiovascular risk factors, the
      multivariate analysis showed that, for each year of experience after completion
      of cardiology training, the probability of adequately indicating the test (OR:
      1.33, 95% CI: 1.29-1.38, P<.001) was statistically significant. CONCLUSIONS: The
      professional experience of the clinical cardiologist is the most important factor
      to perform an appropriate indication of gated-SPECT myocardial perfusion.

PMID- 29198596
TI  - Phenotypic and genetic diversity of Moroccan rhizobia isolated from Vicia faba
      and study of genes that are likely to be involved in their osmotolerance.
AB  - Rhizobia are symbiotic nitrogen-fixing bacteria in root nodules of legumes. In
      Morocco, faba bean (Vicia faba L.), which is the main legume crop cultivated in
      the country, is often grown in marginal soils of arid and semi-arid regions. This
      study examines the phenotypic diversity of rhizobia nodulating V. faba isolated
      from different regions in Morocco for tolerance to some abiotic stresses. A total
      of 106 rhizobia strains isolated from nodules were identified at the species
      level by analysing 16S rDNA. Additionally, for selected strains recA, otsA, kup
      and nodA fragments were sequenced. 102 isolates are likely to belong to Rhizobium
      leguminosarum or R. laguerreae and 4 isolates to Ensifer meliloti. All strains
      tolerating salt concentrations of 428 or 342mM NaCl as well as 127 or 99mM Na2SO4
      were highly resistant to alkaline conditions (pH 10) and high temperature (44
      degrees C). Three strains: RhOF4 and RhOF53 (both are salt-tolerant) and RhOF6
      (salt-sensitive) were selected to compare the influence of different levels of
      salt stress induced by NaCl on growth and on trehalose and potassium
      accumulation. We find a direct correlation between the trehalose contents of the
      rhizobial strains and their osmotolerance.

PMID- 29198598
TI  - Mid-term results of computer-assisted skip pedicle screw fixation for patients
      with Lenke type 1 and 2 adolescent idiopathic scoliosis: A minimum five-year
      follow-up study.
AB  - PURPOSE: In skip pedicle screw fixation for adolescent idiopathic scoliosis
      (AIS), the mid-term effects of reducing screw number on correction and clinical
      results are uncertain. We clarified the mid-term outcomes of this technique in
      patients with Lenke type 1 and 2 AIS. METHODS: Thirty-four patients who underwent
      skip pedicle screw fixation (mean screw density: 1.35 screws) for Lenke type 1
      and 2 AIS were retrospectively reviewed. The follow-up period was at least 5
      years (mean follow-up period: 6.1 years), and the follow-up rate was 89.5%.
      Radiological parameters and clinical symptoms were evaluated before, immediately
      after, and at 2 years and 5 years after surgery. RESULTS: The mean Cobb angle of
      the main thoracic (MT) curve before, immediately after, at 2 years after surgery,
      and at the final 5-year minimum follow-up was 52.5 degrees , 16.4 degrees , 20.5
      degrees , and 19.4 degrees , respectively. The Cobb angle of the MT curve was
      significantly improved immediately after, at 2 years after surgery, and at the
      final follow-up compared with that before surgery (p < 0.01). The mean correction
      rate immediately after surgery was 69.0% and the rate of correction loss at the
      final follow-up was 8.3%. All Scoliosis Research Society-22 patient questionnaire
      (SRS-22r) sub scores 5 years after surgery were significantly improved compared
      with those beforehand (p < 0.01). CONCLUSIONS: Correction using skip pedicle
      screw fixation in AIS was well maintained from the initial follow-up measurements
      to the final follow-up. The SRS-22r sub scores at the final follow-up were
      significantly improved over preoperative levels.

PMID- 29198597
TI  - The position of the aorta relative to the spine in patients with Pott's
      thoracolumbar angular kyphosis.
AB  - STUDY DESIGN: Analyze the position of the aorta in patients with Pott's
      thoracolumbar angular kyphosis by computed tomography. OBJECTIVE: To investigate
      the anatomic position of the aorta relative to spine in patients with Pott's
      thoracolumbar angular kyphosis. SUMMARY OF BACKGROUND DATA: The complication of
      aorta injury is rare in the procedure of spinal osteotomy for the correction of
      Pott's thoracolumbar angular kyphotic deformity. However, there would be a
      disastrous consequence once it happened. Therefore, knowing about the position of
      aorta relative to the spine is of great importance. From the authors' knowledge,
      there are no reports about the research on the position of the aorta relative to
      the spine in patients with Pott's thoracolumbar angular kyphosis. METHODS: Thirty
      patients with Pott's thoracolumbar angular kyphosis and thirty patients without
      spine deformity were recruited and divided into two groups. The CT images of both
      groups from T10 to L1 were obtained to evaluate the left pedicle-aorta angle and
      distance. In the patients with Pott's thoracolumbar angular kyphosis, the
      affected vertebral bodies were fused, so we measured the left pedicle-aorta angle
      and distance of the fused vertebral bodies. For the normal group, we measured the
      left pedicle-aorta angle and distance from T10 to L1 and got the average data,
      then compared with the Pott's group with independent sample t test. The Pearson
      correlation analysis was used to evaluate the association between the change of
      the aortic position and Konstam's angle and LL. RESULTS: The left pedicle-aorta
      angles (-8.95 + 2.89 degrees ) in Pott's group are smaller and the distances
      (6.36 + 0.77 cm) are larger than those in normal group (P < 0.05). In patients
      with Pott's thoracolumbar angular kyphosis, with increased Konstam's angle, the
      left pedicle-aorta angles becomes smaller (r = -0.495, P < 0.05) and the left
      pedicle-aorta distances becomes larger (r = 0.486, P < 0.05). However, there is
      no remarkable correlation between lumbar lordosis and the left pedicle-aorta
      angles or distances. CONCLUSION: In patients with Pott's thoracolumbar angular
      kyphosis, the aorta of the fused vertebrate shifts anteromedially to the
      vertebral body, and the aorta is relatively farther away from the vertebral body
      compared with the normal subjects. Therefore, the surgeon should be aware of the
      change of the position of the aorta to avoid the disastrous complication vessel
      injury.

PMID- 29198599
TI  - Who is the boss? Individual recognition memory and social hierarchy formation in
      crayfish.
AB  - Under laboratory conditions, crayfish establish hierarchical orders through
      agonistic encounters whose outcome defines the dominant one and one, or more,
      submissive animals. These agonistic encounters are ritualistic, based on threats,
      pushes, attacks, grabs, and avoidance behaviors that include retreats and escape
      responses. Agonistic behavior in a triad of unfamiliar, size-matched animals is
      intense on the first day of social interaction and the intensity fades on daily
      repetitions. The dominant animal keeps its status for long periods, and the
      submissive ones seem to remember 'who the boss is'. It has been assumed that
      animals remember and recognize their hierarchical status by urine signals, but
      the putative substance mediating this recognition has not been reported. The aim
      of this work was to characterize this hierarchical recognition memory. Triads of
      unfamiliar crayfish (male animals, size and weight-matched) were faced during
      standardized agonistic protocols for five consecutive days to analyze memory
      acquisition dynamics (Experiment 1). In Experiment 2, dominant crayfish were
      shifted among triads to disclose whether hierarchy depended upon individual
      recognition memory or recognition of status. The maintenance of the hierarchical
      structure without behavioral reinforcement was assessed by immobilizing the
      dominant animal during eleven daily agonistic encounters, and considering any
      shift in the dominance order (Experiment 3). Standard amnesic treatments
      (anisomycin, scopolamine or cold-anesthesia) were given to all members of the
      triads immediately after the first interaction session to prevent individual
      recognition memory consolidation and evaluate its effect on the hierarchical
      order (Experiment 4). Acquisition of hierarchical recognition occurs at the first
      agonistic encounter and agonistic behavior gradually diminishes in the following
      days; animals keep their hierarchical order despite the inability of the dominant
      crayfish to attack the submissive ones. Finally, blocking of protein synthesis or
      muscarinic receptors and cold anesthesia impair memory consolidation. These
      findings suggest that agonistic encounters induces the acquisition of a robust
      and lasting social recognition memory in crayfish.

PMID- 29198600
TI  - Heterogeneous distribution of Culex pipiens, Culex quinquefasciatus and their
      hybrids along the urbanisation gradient.
AB  - The mosquitoes of the Culex pipiens complex, hereafter referred to as the Pipiens
      Assemblage, are vectors of arbovirus of worldwide concern including West Nile and
      St. Louis encephalitis. Given their distinct eco-physiology and vectorial
      capacity, accurate specimen identification and insight in the environmental
      drivers of their distribution are essential for the understanding of disease
      transmission patterns. Using a PCR-based identification protocol, we
      characterized the spatial distribution of Cx. pipiens, Cx. quinquefasciatus and
      their hybrids developing in used tyres located within the overlapping region in
      South America as a function of different estimators of the urbanisation gradient.
      Out of 84 samples collected from tyre piles of 20 sites, we identified 369 larvae
      which corresponded predominantly to Cx. quinquefasciatus (76.4% of immatures) all
      along the gradient but more frequent at the urban end. Cx. pipiens (21.4%) was
      more conspicuous at the low urbanised end but was also present in highly
      urbanised sites, whereas hybrids were collected in very low numbers (2.2%). The
      urbanisation estimator best associated with the heterogeneous occurrence of the
      Pipiens Assemblage members was the proportion of impervious surface 1km around
      each tyre pile, which explained 41.7% of the variability in the data, followed
      closely by the distance to the Capital City (38.3%). Cumulative annual
      precipitation, population number in a 1km radius around each pile and distance to
      the de la Plata River were significantly associated with the distribution of the
      Pipiens Assemblage at lower explanation percentages (20-23%). A thorough
      understanding of the ecological basis and environmental associations of the
      distribution of Pipiens Assemblage members will enable forecasting population
      trends in changing environments to develop effective control measures for
      mosquitoes and the diseases they transmit.

PMID- 29198601
TI  - A short field guide to fibroblast function in immunity.
AB  - Fibroblasts in secondary lymphoid organs, or fibroblastic reticular cells (FRC),
      are gate-keepers of immune responses. Here, we frame how these cells regulate
      immune responses via a three-part scheme in which FRC can setup, support or
      suppress immune responses. We also review how fibroblasts from non-lymphoid
      tissues influence immunity and highlight how they resemble and differ from FRC.
      Overall, we aim to focus attention on the emerging roles of lymphoid tissue and
      non-lymphoid tissue fibroblasts in control of innate and adaptive immunity.

PMID- 29198602
TI  - Gastric Perforation During Bronchoscopy For The Delivery Of Oxygen Therapy By
      Nasopharyngeal Cannula.

PMID- 29198603
TI  - Pulmonary Lesions: Cause Or Consequence Of Respiratory Infection?

PMID- 29198604
TI  - The use of coarsened exact matching to evaluate treatment mode in the rib
      fracture patient.

PMID- 29198605
TI  - Incidence, demographics, and outcomes of nonoperative management of appendicitis
      in the United States.
AB  - BACKGROUND: Appendicitis is the most common intraabdominal surgical emergency in
      the United States, with over 250,000 cases each year. Several recent studies have
      evaluated the efficacy of nonoperative management of appendicitis. We measured
      changes in the treatment of appendicitis in the United States from 1998 to 2014
      and evaluated outcomes in the contemporary cohort of appendicitis cases from 2010
      to 2014. METHODS: The National Inpatient Sample was queried for cases with a
      principal diagnosis of appendicitis. Cases with peritoneal abscesses were
      excluded. We determined trends in management and then compared cases managed
      nonoperatively versus those managed with early operation for demographics and
      outcomes including mortality, total charges, and length of stay using univariate
      analysis, binary logistic regression analysis, and case-control matching.
      RESULTS: Although early operation remains the dominant treatment for acute
      appendicitis in the United States, there is an accelerating trend in nonoperative
      management. Nonoperative management is associated with increased age, number of
      comorbidities, and inpatient diagnoses. In univariate, multiple regression, and
      case-control analysis, nonoperative management is associated with decreased total
      charges but significantly increased risk of mortality. CONCLUSIONS: Elderly
      patients and patients with medical comorbidities are more likely to be treated
      nonoperatively for appendicitis than younger patients. Although previously
      published data support nonoperative management of appendicitis in low-risk
      surgical patients, we suggest that elderly or medically complex patients may
      benefit from early operative treatment of appendicitis and are potentially at
      risk of poor outcomes from nonoperative management.

PMID- 29198607
TI  - The H7N9 viruses have lost most of their previous lineages in the fifth wave.

PMID- 29198606
TI  - Anti-apolipoprotein A-1 autoantibodies are associated with immunodeficiency and
      systemic inflammation in HIV patients.
AB  - OBJECTIVES: To determine the existence of autoantibodies against apolipoprotein A
      1 (anti-apoA-1 IgG) in HIV patients and explore their association with biological
      features of HIV infection and different inflammatory biomarkers. We also
      evaluated their impact on CD4+ lymphocytes survival. METHODS: Anti-apoA-1 IgG
      plasma levels were assessed by ELISA in 237 HIV positive patients from a national
      prospective cohort with no current lipid-lowering therapy. RESULTS: 58% of
      patients were found positive for anti-apoA-1 IgG and were associated with lower
      CD4+ counts, but higher viremia and systemic inflammation. Logistic regression
      analyses indicated that high anti-apoA-1 IgG levels were associated with a 16
      fold increased risk of displaying low CD4+ levels, independent of HIV RNA levels
      and treatment (adjusted Odds ratio [OR]:16.1, 95% Confidence Interval
      [95%CI]:1.80-143.6; p = 0.01), and a 6-fold increased risk of having a detectable
      viremia, independent of antiretroviral treatment (OR:5.47; 95% CI:1.63-18.36; p =
      0.006). In vitro, anti-apoA-1 IgG induced dose and time-dependent CD4+ apoptosis
      that was increased by exposure to HIV RNA. CONCLUSIONS: In HIV patients, anti
      apoA-1 IgG levels are associated with low CD4+ counts, high viremia and a pro
      inflammatory systemic profile. Anti-apoA-1 IgG can promote CD4+ lymphocyte
      apoptosis via undefined pathways.

PMID- 29198608
TI  - Synthesis and evaluation of 18F-hexafluorophosphate as a novel PET probe for
      imaging of sodium/iodide symporter in a murine C6-glioma tumor model.
AB  - Noninvasive imaging of iodide uptake via the sodium/iodide symporter (NIS) has
      received great interest for evaluation of thyroid cancer and reporter imaging of
      NIS-expressing viral therapies. In this study, we investigate 18F-labeled
      hexafluorophosphate (HFP or PF6-) as a high-affinity iodide analog for NIS
      imaging. 18F-HFP was synthesized by radiofluorination of phosphorus
      pentafluoride.N-methylpyrrolidine complex and evaluated in human NIS (hNIS)
      expressing C6 glioma cells and a C6 glioma xenograft mouse model. 18F-HFP was
      obtained in radiochemical yield of 10 +/- 5%, radiochemical purity of >96% and
      specific radioactivity of 604 +/- 18 MBq/umol. Specific uptake of 18F-HFP and
      high affinity of 19F-HFP were observed in hNIS+ C6-glioma cells. PET imaging
      showed robust uptake of 18F-HFP in NIS-expressing tissues (thyroid, stomach, and
      hNIS+ C6 glioma xenografts), and the uptake of 18F-HFP was blocked by NaClO4
      pretreatment. Specific accumulation in hNIS-expressing xenograft (hNIS+) was
      observed relative to isogenic control tumor (hNIS-). Clearance of 18F-HFP was
      predominantly through renal excretion. The biodistribution showed consistent
      results with PET imaging. Minimal bone uptake was observed over 2 h period post
      injection, indicating excellent in vivo stability of 18F-HFP. Although
      improvement in specific radioactivity is desirable, the results indicate that 18F
      HFP is a promising candidate radiotracer for further evaluation for NIS imaging.

PMID- 29198609
TI  - Synthesis and evaluation of biaryl derivatives for structural characterization of
      selective monoamine oxidase B inhibitors toward Parkinson's disease therapy.
AB  - Benzyloxyphenyl moiety is a common structure of highly potent, selective and
      reversible inhibitors of monoamine oxidase B (MAO-B), safinamide and
      sembragiline. We synthesized 4-(benzyloxy)phenyl and biphenyl-4-yl derivatives
      including halogen substituents on the terminal aryl unit. In addition, we
      modified the carbon linker between amine group and the biaryl linked unit. Among
      synthesized compounds, 12c exhibited the most potent and selective MAO-B
      inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a
      competitive inhibitor. In addition, 12c showed greater MAO-B inhibitory activity
      and selectivity compared to well-known MAO-B inhibitors such as selegiline,
      safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson's
      disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)
      immunopositive DAergic neurons and attenuated the PD-associated behavioral
      deficits. This study suggests characteristic structures as a MAO-B inhibitor that
      may provide a good insight for the development of therapeutic agents for PD.

PMID- 29198610
TI  - Evolutionary rate heterogeneity between multi- and single-interface hubs across
      human housekeeping and tissue-specific protein interaction network: Insights from
      proteins' and its partners' properties.
AB  - Integrating gene expression into protein-protein interaction network (PPIN) leads
      to the construction of tissue-specific (TS) and housekeeping (HK) sub-networks,
      with distinctive TS- and HK-hubs. All such hub proteins are divided into multi
      interface (MI) hubs and single-interface (SI) hubs, where MI hubs evolve slower
      than SI hubs. Here we explored the evolutionary rate difference between MI and SI
      proteins within TS- and HK-PPIN and observed that this difference is present only
      in TS, but not in HK-class. Next, we explored whether proteins' own properties or
      its partners' properties are more influential in such evolutionary discrepancy.
      Statistical analyses revealed that this evolutionary rate correlates negatively
      with protein's own properties like expression level, miRNA count, conformational
      diversity and functional properties and with its partners' properties like
      protein disorder and tissue expression similarity. Moreover, partial correlation
      and regression analysis revealed that both proteins' and its partners' properties
      have independent effects on protein evolutionary rate.

PMID- 29198611
TI  - Accurate haplotype imputation with individualized ancestry-adjusted reference
      panels.
AB  - Accurate data imputation requires ethnicity-matched reference panels. However,
      recent admixtures have created mosaic human genomes, different chromosomal
      segments have different ethnic backgrounds, so it is impossible for a single
      ethnicity reference panel to be the matched for data imputation. In this study,
      we explored a novel strategy for imputation. We created individualized mosaic
      reference panel for each person according to his/her ethnic backgrounds at each
      genomic locus. We examined on datasets with 70% missing values on haplotypes and
      50% missing values on genotypes. Results showed that the imputation with mosaic
      references steadily yielded high imputation accuracy and outperforms the other
      strategies. With the mosaic reference panels, the imputation accuracy was 98.8+/
      0.1% (CEU), 98.7+/-0.1% (YRI), 98.5+/-0.1% (CHB), 98.6+/-0.1% (ASW), 97.3+/-0.1%
      (MKK) and 98.2+/-0.1% (MXL). Mosaic reference panel will be one option for future
      missing value imputation in big data era.

PMID- 29198612
TI  - IL-1 family cytokines in cardiovascular disease.
AB  - The interleukin (IL)-1 family is a group of cytokines crucially involved in
      regulating immune responses to infectious challenges and sterile insults. The
      family consists of the eponymous pair IL-1alpha and IL-1beta, IL-18, IL-33, IL
      37, IL-38, and several isoforms of IL-36. In addition, two endogenous inhibitors
      of functional receptor binding, IL-1R antagonist (IL-1Ra) and IL-36Ra complete
      the family. To gain biological activity IL-1beta and IL-18 require processing by
      the protease caspase-1 which is associated with the multi-protein complex
      inflammasome. Numerous clinical association studies and experimental approaches
      have implicated members of the IL-1 family, their receptors, or component of the
      processing machinery in underlying processes of cardiovascular diseases (CVDs).
      Here we summarize the current state of knowledge regarding the pro-inflammatory
      and disease-modulating role of the IL-1 family in atherosclerosis, myocardial
      infarction, aneurysm, stroke, and other CVDs. We discuss clinical evidence,
      experimental approaches and lastly lend a perspective on currently developing
      therapeutic strategies involving the IL-1 family in CVD.

PMID- 29198613
TI  - Mechanochemically induced solid state transformations: The case of raloxifene
      hydrochloride.
AB  - Raloxifene hydrochloride is a benzothiophene derivative mainly used in the
      prevention and treatment of osteoporosis, but exhibits a low bioavailability
      hindered by its poor water solubility. In this study, a mechanochemical approach
      based on neat and liquid-assisted grinding was applied to produce new solid forms
      of raloxifene hydrochloride. The solids obtained were characterized by several
      solid-state techniques, such as powder X-ray diffraction, thermal analysis,
      infrared and Raman spectroscopy. These results showed that depending on the
      processing conditions solvated or amorphous forms can be produced. The thermal
      stability of the new forms was also investigated showing that the new forms
      convert back into the raw material form, as observed by Raman spectroscopy, which
      was successfully used to discriminate amorphous and crystalline forms, as well
      as, to monitor in situ the recrystallization process. Furthermore, the solubility
      of the new forms was evaluated, showing the clear advantage of the amorphous
      form, when compared with the currently marketed salt.

PMID- 29198614
TI  - Informed Consent for Radiation in Interventional Radiology Procedures.
AB  - PURPOSE: To explore the patient perception on radiation-related cancer risk from
      interventional radiology (IR) procedures and whether informed radiation consent
      is warranted. METHODS: A multiple-choice survey was prospectively administered to
      68 adults undergoing a body or neuro-IR procedure with ionizing radiation
      exposure. Subgroup analysis with chi-square or Fisher exact test was performed
      based on patient past IR history (P < .05). RESULTS: A total of 81% of patients
      wanted to be informed if there was a radiation-related 3% increased cancer risk
      over 5 years. Although 55% considered 3% a small risk, 28% wanted to further
      discuss the risks and alternate options, and 15% would have only proceeded if it
      were a life-saving procedure: 89%, 80%, and 67% of patients wanted to be informed
      with exposure risks of 1 in 100, 1 in 1000, and 1 in 10,000, respectively. Only
      53% were aware they were going to be exposed to radiation, irrespective of past
      IR history (P = .15). Most patients believed radiation consent should include
      radiation-related cancer risks (85%). No past IR history was significantly
      associated with wanting consent to include cancer-related risk (100% vs 76%; P =
      .01) and deterministic risks (70% vs 41%; P = .04). A majority (69%) believed
      both the referring physician and the interventional radiologist were responsible
      for obtaining radiation consent, and 65% of patients wanted verbal consent
      followed by signed written consent, regardless of past IR history. CONCLUSIONS:
      Many patients want to discuss cancer-related radiation risks with both
      radiologists and physicians. Informed radiation consent should be considered for
      procedures with high anticipated radiation doses.

PMID- 29198615
TI  - Reappraising newborn screening for cobalamin C disorder.

PMID- 29198616
TI  - Incidence of hypoglycemia in newborns at risk and an audit of the 2011 American
      academy of pediatrics guideline for hypoglycemia.
AB  - BACKGROUND: Hypoglycemia is low blood glucose level that may negatively affect
      neurological and developmental prognosis. The American Academy of Pediatrics
      (AAP), Committee on Fetus and Newborn defined the safe glucose concentrations in
      the 2011 guideline for newborns at risk for hypoglycemia. This study aimed to
      investigate the incidence and associated risk factors for hypoglycemia in newborn
      infants having risk and to assess compliance with the AAP guideline. METHODS:
      According to 2011 AAP guideline for hypoglycemia, the newborns at risk for
      hypoglycemia included in this study were divided to four groups [infant of
      diabetic mother (IDM), large-for-gestational-age (LGA) infants, small-for
      gestational-age (SGA) infants, and late preterm infants (LPI)]. RESULTS: Of the
      207 newborn infants, there were 12 cases in IDM group (5.7%), 79 cases in LGA
      group (38.1%), 66 cases in SGA group (31.8%) and 50 cases in LPI group (24.1%).
      The incidences of hypoglycemia in these four groups were 2 (16.6%), 10 (12.7%), 8
      (12.2%) and 17 (34%), respectively. Although the gender, delivery method, birth
      weight and 5-min Apgar score at 5-min were not found to be associated with
      hypoglycemia (P > 0.05), lower gestational age was determined to be associated
      with higher incidence of hypoglycemia (P = 0.02). Median first feeding time was
      55 min and time between first nutrition and blood glucose measurement was 30 min
      in all cases. CONCLUSION: Highest risk for hypoglycemia in early postnatal period
      was present especially in LPI group. Our compliance levels with the AAP guideline
      was found to be satisfactory.

PMID- 29198617
TI  - McCune-Albright Syndrome: Diagnosis and clinical course in eleven patients.

PMID- 29198618
TI  - Analysis instruments for the performance of Advanced Practice Nursing.
AB  - Advanced Practice Nursing has been a reality in the international context for
      several decades and recently new nursing profiles have been developed in Spain as
      well that follow this model. The consolidation of these advanced practice roles
      has also led to of the creation of tools that attempt to define and evaluate
      their functions. This study aims to identify and explore the existing instruments
      that enable the domains of Advanced Practice Nursing to be defined. A review of
      existing international questionnaires and instruments was undertaken, including
      an analysis of the design process, the domains/dimensions defined, the main
      results and an exploration of clinimetric properties. Seven studies were analysed
      but not all proved to be valid, stable or reliable tools. One included tool was
      able to differentiate between the functions of the general nurse and the advanced
      practice nurse by the level of activities undertaken within the five domains
      described. These tools are necessary to evaluate the scope of advanced practice
      in new nursing roles that correspond to other international models of
      competencies and practice domains.

PMID- 29198619
TI  - New mosaic tiles in childhood hereditary autoinflammatory disorders.
AB  - The protean clinical phenotypes of hereditary autoinflammatory disorders (HAID)
      are caused by abnormal activation of innate immunity and consist of seemingly
      unprovoked inflammatory flares localized to multiple organs, such as the skin,
      joints, serosal membranes, gut, and central nervous system. Different mutations
      in genes implied in activation of the interleukin-1 (IL-1)-structured
      inflammasome, cytoskeletal signaling and apoptosis contribute to the pathogenesis
      of different HAID, which mostly start in childhood with self-limited flares
      unrelated to infectious agents, autoantibody production or autoreactive cells.
      Though IL-1 remains pivotal in many inflammasome-mediated diseases, other
      cytokinopathies involving IL-18, nuclear factorkappa-B, interferons, and tumor
      necrosis factor have provided new horizons in the definition of HAID of children:
      the list of HAID has expanded as a consequence of a better understanding of their
      pathogenetic molecular mechanisms and also application of new genetic
      technologies. However, diagnosis of most HAID is clinical and focused on several
      evidence-based criteria sets: their discrimination remains challenging for
      unexperienced pediatricians as there are no universally accepted algorithms, and
      a still relevant number of patients may linger without any clarifying genetic
      analysis, whose interpretation combined with processing of treatment options
      should be discussed on a multidisciplinary basis.

PMID- 29198620
TI  - The role of HMGB1 in heart transplantation.
AB  - There has been significant progress in the field of heart transplantation over
      the last 45 years. Although the role of adaptive immunity in heart allograft
      rejection has been extensively studied for decades, there is increasing evidence
      that suggests that the innate immune system also contributes to the development
      of heart allograft rejection. The high-mobility group box (HMGB) proteins,
      particularly HMGB1, are self-derived innate immune activators that have multiple
      functions in the regulation of immunity and inflammation. Recent discoveries have
      illustrated the close link between HMGB1 and heart allograft rejection. In this
      review, we summarize current knowledge of the function of HMGB1 as a ligand that
      can evoke inflammatory responses and ultimately cause rejection after heart
      transplantation.

PMID- 29198621
TI  - Innate immune receptors for cross-presentation: The expanding role of NLRs.
AB  - A critical role of pattern recognition receptors (PRRs) is to influence adaptive
      immune responses by regulating antigen presentation. Engagement of PRRs in
      dendritic cells (DCs) increases MHC class I antigen presentation and CD8+ T-cell
      activation by cross-presented peptides but the molecular mechanisms underlying
      these effects are not completely understood. Studies looking at the role of PRRs
      in cross-presentation have been largely limited to TLRs but the role of other
      PRRs such as cytosolic nucleotide-binding oligomerization domain-like (NOD-like)
      receptors remains particularly enigmatic. Here we discuss recent evidence of the
      role of PRRs on cross-presentation and consider how cytosolic NLR-associated
      pathways, such as NOD2, may integrate these signals resulting in effective
      adaptive CD8+ T cells responses.

PMID- 29198622
TI  - On-line health seeking activity of older adults: an integrative review of the
      literature.
AB  - The internet is increasingly used to provide health information. Supporting older
      people to access on-line health information requires understanding their current
      usage and possible barriers and facilitators. Methods involved searching three
      databases. Inclusion criteria were: (i) articles published within 10 years; (ii)
      people aged >65; (iii) explored reasons for older people accessing on-line health
      information and (iv) in English. Eight articles met these criteria. Older people
      use on-line health information to learn about a disease, medication, treatment,
      or healthy living. Factors influencing usefulness of on-line health information
      included demographics, health status, trust in the information, lack of skills
      using the internet and attitudes of health professionals. Findings indicate that
      while older people access on-line health information there are barriers: Low
      trust, financial barriers, lack of familiarity with the internet and low health
      literacy levels. Implications for nursing include working in partnership with
      older people to assist them to identify appropriate on-line information.

PMID- 29198623
TI  - Thoracoscopic Surgery Versus Thoracotomy for Lung Cancer: Short-Term Outcomes of
      a Randomized Trial.
AB  - BACKGROUND: Safety and short-term efficacy of video-assisted thoracoscopic
      surgery (VATS) for early-stage non-small lung cancer (NSCLC) has been
      demonstrated by observational studies previously. However, these outcomes have
      never been verified by a large randomized controlled trial (RCT). The aim of our
      RCT was to confirm that VATS is not inferior or even superior to open operation
      for early-stage NSCLC in terms of short-term and oncologic efficacy. METHODS: The
      trial was undertaken at five tertiary hospitals. Patients aged between 18 and 75
      years with clinically early-stage NSCLC were randomly assigned to the VATS and
      axillary thoracotomy groups. Lobectomy plus mediastinal lymph node dissection was
      standard surgical intervention. Because patients continue to be followed up for
      oncologic outcome, the short-term perioperative outcomes would be reported here.
      RESULTS: Between 2008 and 2014, 508 patients were recruited and 425 were eligible
      for analyses (215 VATS and 210 axillary thoracotomy). Eight VATS procedures were
      converted to open operation intraoperatively (3.72%). Median operation time with
      VATS was significantly less than axillary thoracotomy (150 versus 166 minutes, p
      = 0.009). In addition, VATS was associated with less intraoperative blood loss (p
      = 0.001). There was no difference for postoperative pleural drainage, length of
      hospitalization, and rates of morbidity and mortality. Cancer residual margins
      were found in 1 patient with VATS and 5 with axillary thoracotomy (p = 0.128).
      The yield of lymph nodes from either surgical approach was similar (p = 0.389).
      CONCLUSIONS: Our study demonstrates that VATS lobectomy is safe and reliable to
      treat NSCLCs, and it may be superior to axillary thoracotomy for operation time
      and intraoperative blood loss. ClinicalTrials.gov identifier: NCT01102517.

PMID- 29198624
TI  - Stereotactic Body Radiation Therapy Versus Surgery for Early Lung Cancer Among US
      Veterans.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) has been proposed as a
      potential alternative to surgery for early lung cancer, although we lack well
      powered prospective randomized data comparing these treatments, and existing
      studies suffer from incomplete information on confounders that can bias results.
      Here, we evaluated the comparative effectiveness of surgery and SBRT in lung
      cancer treatment using a large extensively detailed database from the Veteran's
      Affairs system. METHODS: We identified veterans with biopsy-proven clinical stage
      I non-small cell lung cancer diagnosed between 2006 and 2015 from within the
      Veteran's Affairs Informatics and Computing Infrastructure. We compared cancer
      specific survival among patients receiving lobectomy, sublobar resection, or SBRT
      using univariable and multivariable competing risk analyses. Multivariable
      analyses adjusted for confounders including preoperative pulmonary function,
      smoking status, comorbidity, and staging workup procedures. RESULTS: In all,
      4,069 patients were included (449 SBRT, 2,986 lobectomy, 634 sublobar resection).
      Unadjusted analysis found higher immediate postprocedural mortality in the
      surgery groups compared with the SBRT group. The multivariable analysis
      considering long-term survival found higher cancer-specific mortality for SBRT
      compared with lobectomy (subdistribution hazard ratio 1.45, 95% confidence
      interval: 1.09 to 1.94, p = 0.01), although no survival difference between SBRT
      and sublobar resection (subdistribution hazard ratio 1.25, 95% confidence
      interval: 0.93 to 1.68, p = 0.15). CONCLUSIONS: Among a large cohort of early
      stage lung cancer patients, we found that lobectomy had improved survival
      compared with SBRT, although we found no survival difference between sublobar
      resection and SBRT. Despite these findings, the potential for unmeasured
      confounding remains and prospective randomized trials are needed to better
      compare these treatment modalities.

PMID- 29198625
TI  - Transversus Abdominis Plane Block Improves Perioperative Outcome After
      Esophagectomy Versus Epidural.
AB  - BACKGROUND: Pain control is challenging during esophagectomy. An epidural is
      commonly used, but the sympathetic blockade can have unintended consequences such
      as hypotension or delayed return of bowel function. A transversus abdominis plane
      (TAP) block has the potential to control upper abdominal pain without these
      adverse consequences. We aimed to compare bilateral TAP blocks with patient
      controlled analgesia (PCA) for immediate management after esophagectomy with a
      cohort using a thoracic (T5 to T8) epidural. METHODS: This was a retrospective
      review of patients undergoing esophagectomy between 2012 and 2016. Primary
      outcomes were pain scores (0 to 10) assessed at 24, 48, and 72 hours for adequacy
      of pain control. Secondary outcomes were volume resuscitation at 72 hours,
      hypotension (systolic blood pressure <90 mm Hg), length of stay (LOS), return of
      bowel function, and complications. RESULTS: Sixty-one patients underwent
      esophagectomy using bilateral TAP block and PCA (n = 32) or thoracic (T5 to T8)
      epidural (n = 29). Overall pain scores were not statistically different between
      the TAP group and the epidural group averaged over 72 hours (4.98 versus 4.39, p
      = 0.09). During the initial 72 hours after operation, hypotension was less
      prevalent in the TAP group (25% versus 76%, p < 0.05) with lower crystalloid
      resuscitation needs. The LOS in the intensive care unit (3.2 days versus 4.6
      days, p < 0.05) and return of bowel function (5 days versus 6.7 days, p < 0.05)
      were considerably shorter in the TAP group. Pulmonary complications were similar.
      CONCLUSIONS: TAP blocks with a PCA is an alternative option for pain control in
      patients undergoing esophagectomy and may reduce hypotension and need for volume
      resuscitation with similar pulmonary complications.

PMID- 29198626
TI  - The Impact of Distal Stent Graft-Induced New Entry on Aortic Remodeling of
      Chronic Type B Dissection.
AB  - BACKGROUND: In chronic type B aortic dissection, late distal stent graft-induced
      new entry (SINE) has a possible negative role in long-term aortic remodeling.
      This study aimed to investigate the impact of SINE occurrence on survival by
      evaluating true and false lumen remodeling in thoracic and abdominal segments at
      midterm surveillance. METHODS: This study enrolled 65 patients with chronic type
      B aortic dissection (DeBakey type IIIb), who had received hybrid thoracic
      endovascular aortic repair (TEVAR) and had completed surveillance for at least 3
      years. The 3-year survival rate was 84.7%. The patients were classified into non
      SINE (n = 47) and SINE (n = 18) groups. Serial computed tomography scans were
      used to analyze volumetric change, true and false lumens, and thrombus volume
      from arch to aortic bifurcation level. RESULTS: The SINE event occurred at a
      median of 22.5 months. In the SINE group, there was a significant interruption of
      the abdominal true lumen expansion in the second year (median 0.01 [interquartile
      range (IQR), -0.03 to 0.12] in the non-SINE group versus median -0.04 [IQR, -0.12
      to 0.04] in the SINE group; p = 0.014). There was a significantly worse thoracic
      false lumen remodeling in the SINE group compared with the non-SINE group in the
      third year after the SINE event occurred (median 0 [IQR, -0.09 to 0.05] in the
      non-SINE group versus median 0.06 [IQR, 0 to 0.13] in the SINE group; p = 0.038).
      CONCLUSIONS: For chronic aortic dissection, late occurrence of distal SINE could
      influence abdominal true lumen expansion and thoracic false lumen shrinkage.
      Early reintervention for distal SINE could improve aortic remodeling in chronic
      aortic dissection.

PMID- 29198627
TI  - Analytic Morphomics Predict Outcomes After Lung Transplantation.
AB  - BACKGROUND: The purpose of this study was to identify morphomic factors on
      standard, pretransplantation computed tomography (CT) scans associated with
      outcomes after lung transplantation. METHODS: A retrospective review of 200
      patients undergoing lung transplantation at a single institution from 2003 to
      2014 was performed. CT scans obtained within 1 year before transplantation
      underwent morphomic analysis. Morphomic characteristics included lung, dorsal
      muscle group, bone, and subcutaneous and visceral fat area and density. Patient
      data were gathered from institutional and United Network for Organ Sharing
      databases. Outcomes, including initial ventilator support greater than 48 hours,
      length of stay, and survival, were evaluated using univariate and multivariable
      analyses. RESULTS: On multivariable Cox regression, subcutaneous fat/total body
      area (hazard ratio [HR] 0.60, p = 0.001), lung density 3 volume (HR 0.67, p =
      0.013), and creatinine (HR 4.37, p = 0.010) were independent predictors of
      survival. Initial ventilator support more than 48 hours was associated with
      decreased vertebral body to linea alba distance (odds ratio [OR] 0.49, p = 0.002)
      and Zubrod score 4 (OR 14.0, p < 0.001). Increased bone mineral density (p <
      0.001) and increased cross-sectional body area (p < 0.001) were associated with
      decreased length of stay, whereas supplemental oxygen (p < 0.001), bilateral
      transplantation (p = 0.002), cardiopulmonary bypass (p < 0.001), and Zubrod score
      3 (p < 0.001) or 4 (p = 0.040) were associated with increased length of stay.
      CONCLUSIONS: Morphomic factors associated with lower metabolic reserve and
      frailty, including decreased subcutaneous fat, bone density, and body dimensions
      were independent predictors of survival, prolonged ventilation, and increased
      length of stay. Analytic morphomics using pretransplantation CT scans may improve
      recipient selection and risk stratification.

PMID- 29198628
TI  - Revision of Failed Prior Nuss in Adult Patients With Pectus Excavatum.
AB  - BACKGROUND: Minimally invasive repair of pectus excavatum (MIRPE) has been
      extended to repair of defects in adults, with reported higher complication rates
      and outcome failures. The optimal revision for a prior failed MIRPE in an adult
      has not been identified. We review our experience for this adult population.
      METHODS: A retrospective review was performed of 129 patients (age >=18 years)
      who underwent revision after a failed pectus excavatum (PE) repair from December
      2010 through December 2016. RESULTS: In total, 47 of the 129 (36%) revision
      patients had a prior failed MIRPE, with 98% presenting for revision because of
      inadequate correction after their initial repair. The median age was 28 years
      (range, 18 to 54 years), and 77% were men. Thirty-one (66%) patients had
      indwelling pectus support bars at the revision procedure. Mean time from initial
      MIRPE to the revision procedure was 3.34 +/- 2.9 years. A modified MIRPE was
      successful in 39 (83%) patients. Hybrid repair with the addition of osteotomy
      cuts and/or titanium plating was required in 8 patients for an adequate revision.
      Multiple (2 bars, 62%; 3 bars, 38%), shorter (median, 13.5 inches versus 15.0
      inches) bars were used for the revision versus earlier repair. Substantial lysis
      of intrathoracic adhesions was required in 40 (85%) patients, with a median
      operative time for revision MIRPE of 169 +/- 66 minutes; median operative time
      for hybrid procedures, 314 +/- 74 minutes. CONCLUSIONS: A modified MIRPE can be
      successfully used in most adults to revise a failed prior MIRPE.

PMID- 29198629
TI  - Aortic Replacement After TEVAR-Diameter Correction With Modified Use of the Siena
      Prosthesis.
AB  - BACKGROUND: To report a new technique for diameter correction in patients after
      thoracic endovascular aortic repair (TEVAR) with large stent-grafts using the
      Vascutek Siena 4-branch collared prosthesis (Vascutek Terumo, Inchinnan,
      Scotland, UK) in patients undergoing thoracoabdominal (TA) aortic replacement.
      METHODS: Within a 24-month period, 39 patients underwent TA replacement at our
      center. Of these, 6 patients had undergone previous TEVAR with large stent-grafts
      (42 to 48 mm diameter). Indications for TEVAR were aneurysm formation in 3
      patients and residual type B aortic dissection (status post repair of type A
      dissection) in 3 patients. In these patients, the Vascutek Siena 4-branch
      prosthesis was used in a reversed fashion, removing the elephant trunk portion
      and using the sewing collar for diameter correction at the anastomotic site.
      RESULTS: No 30-day mortality and no stroke or symptomatic spinal cord ischemia
      was observed. Median diameter of the TEVAR graft at the anastomotic site was 44
      mm. Median size of the Siena graft used was 26 mm. Diameter correction was
      successfully achieved in all patients by tailoring the sewing collar of the Siena
      4-branch prosthesis to the individual need according to the diameter of the
      distal end of the stent-graft. CONCLUSIONS: Using the sewing collar of the
      Vascutek Siena 4-branch prosthesis for diameter correction in patients undergoing
      TA replacement after previous TEVAR with large stent-grafts adds a useful adjunct
      to the armamentarium of options in a growing patient population.

PMID- 29198630
TI  - Long-Term Survival in Patients Receiving a Continuous-Flow Left Ventricular
      Assist Device.
AB  - BACKGROUND: Long-term survivors after implantation of left ventricular assist
      devices (LVADs) are increasing in prevalence. We describe the characteristics and
      outcomes in patients surviving longer than 4 years on LVAD support. METHODS: We
      performed a multicenter, retrospective analysis of patients surviving at least 4
      years on continuous-flow LVAD (CF-LVAD) support with a HeartMate II at centers
      participating in the Evolving Mechanical support Research Group. RESULTS: Between
      2005 and 2010, 156 long-term survivors were identified with a mean survival of
      7.1 years (95% confidence interval: 6.7 to 7.5 years). The mean age was 58.2 +/-
      15.2 years and 30.1% were women. Readmission rate was low at 1.1 events per
      patient per year with the most common reasons leading to readmission being
      infection (0.10 readmissions per patient per year) and gastrointestinal bleeding
      (0.07 readmissions per patient per year). Two years after implantation, 97% of
      patients were either New York Heart Association functional class I or II, with
      92% at 4 years. CONCLUSIONS: Patients surviving 4 years on CF-LVAD support can
      anticipate ongoing long-term survival with sustained improvements in
      functionality and low rates of rehospitalization.

PMID- 29198631
TI  - Elective David I Procedure Has Excellent Long-Term Results: 20-Year Single-Center
      Experience.
AB  - BACKGROUND: We present our results after elective, isolated David I procedures
      over the past 20 years. METHODS: Between 1993 and 2015, 197 patients (mean age 46
      +/- 17 years, 73% men) underwent isolated aortic valve reimplantation using
      straight tube grafts (David I procedure). Sixty patients (31%) had Marfan
      syndrome, and 24 (12%) had a bicuspid aortic valve. Twenty-four patients (12%)
      were operated through upper mini-sternotomy. RESULTS: There were no perioperative
      deaths. Stroke rate was 1% (2 of 197). Discharge echocardiography showed none to
      trivial aortic regurgitation (AR) in 71% (139 of 197 patients) and mild AR in 26%
      (51 of 197 patients). Thirty-two patients (16%) died during follow-up (9.0 +/-
      5.5 years after operation). One death was aortic valve related. Twenty-six
      patients (13%) underwent aortic valve reoperations during follow-up (5.5 +/- 5.0
      years after operation). Late endocarditis occurred in 2 patients (1.0%). More
      than trivial AR at discharge predicted a higher reoperation rate. In 144 non
      reoperated survivors, echocardiography showed none to trivial AR in 56 (39%),
      mild AR in 53 (37%), moderate AR in 19 (6.3%), and severe AR in 4 (2.7%) of the
      patients after 12 +/- 5.3 years. CONCLUSIONS: The valve-sparing David I procedure
      has excellent short- and long-term results. Erosion due to supposed leaflet
      contact with the straight tube graft was not observed in any patient, proving
      that using a straight graft has no negative impact on the leaflets. The "spared
      valve" (being native living tissue) seems to be more resistant to infection than
      prosthetic valves.

PMID- 29198632
TI  - Prognostic factors predicting survival in incurable stage IV colorectal cancer
      patients who underwent palliative primary tumor resection. Retrospective cohort
      study.
AB  - BACKGROUND: The aim of this study is to estimate prognostic factors predicting
      survival in patients with incurable stage IV colorectal cancer (CRC), who
      underwent palliative primary tumor resection (PTR) with chemotherapy. MATERIALS
      AND METHODS: We retrospectively performed an analysis using clinicopathological
      parameters of 103 patients with incurable stage IV CRC, who underwent palliative
      PTR with chemotherapy between 2006 and 2010. Prognostic factors associated with
      overall survival (OS) were evaluated by univariate and multivariate analyses.
      RESULTS: The median follow-up time was 17.5 months (range 2.4-60.5) for the total
      cohort (n = 103). There were five independent factors related to OS in univariate
      analysis (body mass index, tumor differentiation, pT, pN stage and local
      clearance of the primary tumor). A multivariate analysis revealed that pT, pN and
      local clearance of the primary tumor were prognostic factors related to OS.
      Median survival months (95% CI) were pT1, 2, 3: 21.5 (16.23-26.77) months vs.
      pT4: 13.73 (9.94-17.53) months, pN-: 29.7 (22.55-35.99) months vs. pN+: 17.1
      (15.0-19.41) months and R0: 18.57 (16.65-20.48) months vs. R1, 2: 12.43 (9.95
      14.91) months. CONCLUSION: Locally advanced primary tumor (high pT stage,
      positive regional lymph node, and local residual primary tumor) was associated
      with poorer OS in incurable stage IV CRC patients, who underwent palliative PTR
      with chemotherapy. The PTR appears to result in better OS in patients with a
      primary tumor that is not locally advanced.

PMID- 29198633
TI  - Intraoperative Echocardiographic Assessment of Prosthetic Valves: A Practical
      Approach.

PMID- 29198634
TI  - Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces
      Blood Requirements in Cardiac Transplantation.
AB  - OBJECTIVE: Assessing the efficacy of intraoperative 4-factor prothrombin complex
      concentrate (4F-PCC) use in blood product utilization, time to chest closure,
      intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic
      complications, renal injury and mortality in left ventricular assist device
      (LVAD) patients on home anticoagulation therapy with warfarin, undergoing
      orthotopic heart transplantation (OHT). DESIGN: Retrospective analysis of OHT
      patients at Tufts Medical Center from May 2013 to October 2016. SETTING: Single
      institution, university hospital setting. PARTICIPANTS: Patients with preexisting
      LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42
      patients no 4F-PCC). INTERVENTIONS: Warfarin reversal using 4F-PCC in patients
      with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing
      partitioned such that one-third was given pre-CPB and two-thirds were given post
      CPB. MEASUREMENTS AND MAIN RESULTS: The 4F-PCC group required less plasma (6 [IQR
      4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p
      < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and
      had a shorter time to chest closure (618.8 +/- 111.4 v 547.9 +/- 110.1 minutes, p
      = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1]
      U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No
      thrombotic complications occurred. CONCLUSIONS: Replacing plasma with 4F-PCC to
      reverse preoperative warfarin anticoagulation during OHT was associated with a
      shorter time to chest closure and less blood product utilization, without an
      increase in acute kidney injury, thromboembolic complications, or death.

PMID- 29198635
TI  - Systems analysis of voluntary reported anaesthetic safety incidents occurring in
      a university teaching hospital.
AB  - OBJECTIVE: To identify factors contributing to the development of anaesthetic
      safety incidents. STUDY DESIGN: Prospective, descriptive, voluntary reporting
      audit of safety incidents with subsequent systems analysis. ANIMALS: All animals
      anaesthetized in a multispecies veterinary teaching hospital from November 2014
      to October 2016. METHODS: Peri-anaesthetic incidents that risked or caused
      unnecessary harm to an animal were reported by anaesthetists alongside animal
      morbidity and mortality data. A modified systems analysis framework was used to
      identify contributing factors from the following categories: Animal and Owner,
      Task and Technology, Individual, Team, Work Environmental, and Organizational and
      Management. The outcome was graded using a simple descriptive scale. Data were
      analysed using Pearson's Chi-Square test for association and univariable and
      multivariable logistic regression analysis. RESULTS: Totally, 3379 anaesthetics
      were performed during the audit period. Of these, 174 incident reports were
      analysed, 163 of which impacted safe veterinary care and 26 incidents were
      considered to have had major or catastrophic outcomes. Incident outcome was
      believed to have been limited by anaesthetist intervention in 104 (63.8%) cases.
      Various factors were identified as: Individual in 123 (70.7%), Team in 108
      (62.1%), Organizational and Management in 94 (54.0%), Task and Technology in 80
      (46.0%), Work Environmental in 53 (30.5%) and Animal and Owner in 36 (20.7%)
      incidents. Individual factors were rarely seen in isolation. Significant
      associations were identified between Experience and Supervision, X2 (1,
      n=174)=54177, p=0.001, Failure to follow a standard operating procedure and Task
      Management, X2 (2, n=174)=11318, p=0.001, and Staffing and Poor Scheduling, X2
      (1, n=174)=36742, p=0.001. Animal Condition [odds ratio (OR)=16210, 95%
      confidence interval (CI)=5573-47147)] and anaesthetist Decision Making (OR=3437,
      95% CI=1184-9974) were risk factors for catastrophic and major outcomes.
      CONCLUSIONS AND CLINICAL RELEVANCE: Individual factors contribute to many safety
      incidents but tend to occur concurrently with other factors. Anaesthetist
      intervention limits the consequences of incidents for most animals.

PMID- 29198636
TI  - Prolonged diuretic and saluretic effect of nothofagin isolated from Leandra
      dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats: Role of
      antioxidant system and renal protection.
AB  - Although the acute diuretic effect of nothofagin has been recently demonstrated,
      its effects after dose-repeated treatment have not yet been explored. For that,
      male Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) were
      orally treated, once a day, with vehicle (VEH: distilled water; 1 ml/kg),
      hydrochlorothiazide (HCTZ; 10 mg/kg) or nothofagin (NOT; 1 mg/kg). The cumulative
      diuretic index and urinary electrolytes excretion were measured each 24 h. On the
      last day of the experiment (7th day), urine, blood and kidney samples were
      collected for biochemical and molecular analyzes. The urinary volume of both NTR
      and SHR were significantly increased with the treatment with NOT (from the second
      to the seventh day of treatment), with final values reaching an increase of 56%
      and 82%, respectively, when compared with VEH-treated group. This effect was
      associated with increased levels of urinary excretion of Na+ and Cl-, without any
      changes on K+ excretion. None of the treatments modified urinary pH or density
      values. Importantly, neither the NOT nor the HCTZ caused any change in body
      weight following the dose-repeated treatment, and also did not provoke an
      electrolytic disturbance. Regarding the renal analyzes, when compared with the
      vehicle-treated NTR group, the activity of superoxide dismutase (SOD) and the
      reduced glutathione (GSH) levels in kidney homogenates of the SHR group were
      decreased, while the generation of lipid hydroperoxides were significantly
      increased. The daily treatment with NOT was able to restore the GSH levels and
      SOD activity, as well as reduced the lipoperoxidation in the kidney homogenates
      obtained from SHR animals. Finally, NOT significantly augmented the levels of
      nitrite, a marker of nitric oxide production, in the plasma obtained from SHR
      group when compared with the vehicle-treated only NTR. This study revealed the
      prolonged diuretic and saluretic effect of nothofagin in normotensive and
      hypertensive rats. Our data also showed the renal protective effects of
      nothofagin by the improvement of antioxidative capacity, as well as by the
      augmented bioavailability of plasma nitric oxide in the hypertensive group.

PMID- 29198637
TI  - [Current status of noninvasive hemodynamics in hypertension].
AB  - Hypertension is a haemodynamic disorder resulting from a persistent mismatch
      between cardiac output and peripheral resistance. Hypertension undergoes
      haemodynamic progression during its natural history. Impedance cardiography is a
      method of evaluating the cardiovascular system that obtains haemodynamic
      information from beat to beat through the analysis of variations in the impedance
      of the thorax on the passage of an electric current. Impedance cardiography
      unmasks the haemodynamic deterioration underlying the increase in blood pressure
      as age and systolic blood pressure increases. This method may help to improve
      blood pressure control through individualized treatment with reduction of
      peripheral resistance, maintenance of cardiac output or its increase, improvement
      of arterial compliance and preservation of organ-tissue perfusion. It is useful
      in the management of patients with resistant hypertension, since a greater
      percentage of patients controlled with changes in the treatment in relation to
      the haemodynamic measurements are obtained. Impedance cardiography is important
      and has prognostic utility in relation to a haemodynamic deterioration pattern
      and increased cardiovascular events.

PMID- 29198638
TI  - Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical
      Procedures.
AB  - BACKGROUND: There is a paucity of data to inform appropriate opioid prescribing
      for patients who are discharged after a hospital admission for a surgical
      procedure. STUDY DESIGN: We studied 333 inpatients discharged to home after
      bariatric, benign foregut, liver, pancreas, ventral hernia, and colon surgery.
      Chronic opioid users or patients who had complications were excluded. Home opioid
      usage was quantified in 90% of the remaining patients by questionnaires and phone
      surveys. RESULTS: Eighty-five percent of patients were prescribed an opioid and
      38% of prescribed opioid pills were taken. Fifteen opioid pills satisfied the
      opioid needs of 88% of patients discharged on postoperative day (POD) 1. For
      patients discharged after POD 1, in multivariate analysis, the number of opioid
      pills used at home was associated with the number taken the day before discharge
      (p < 0.0001) and patient age (p = 0.006), but not the type of surgery. Forty-one
      percent of patients took no opioids the day before discharge, 33% took 1 to 3,
      and 26% took more than 4 pills. Eighty-five percent of patients' home opioid
      requirements would be satisfied using the following guideline: if no opioid pills
      are taken the day before discharge, no prescription is needed; if 1 to 3 opioid
      pills are taken the day before discharge, then a prescription for 15 opioid pills
      is given at discharge; and if 4 or more pills are taken the day before discharge,
      then a prescription for 30 opioid pills is given at discharge. If these
      guidelines were used, the number of opioid pills prescribed would decrease by
      40%. CONCLUSIONS: For patients admitted after surgical procedures, post-discharge
      opioid use is best predicted by usage the day before discharge. Use of this
      guideline could decrease opioid prescriptions substantially and effectively treat
      patients' pain.

PMID- 29198639
TI  - Baseline Multiparametric MRI for Selection of Prostate Cancer Patients Suitable
      for Active Surveillance: Which Features Matter?
AB  - INTRODUCTION: Increasing evidence has supported the use of multiparametric
      magnetic resonance imaging (mpMRI) for the detection of prostate cancer. However,
      its role in selecting patients clinically suitable for active surveillance (AS)
      is still in development. We aimed to find relevant mpMRI features that might be
      helpful for refinement of the selection of low-risk prostate cancer patients for
      AS. We also evaluated the interobserver variability in reporting prostate mpMRI
      features. PATIENTS AND METHODS: From 2008 to 2012, 135 patients were selected for
      AS using Epstein criteria. Baseline mpMRI studies were performed within 3 months
      of recruitment and reviewed by 2 radiologists who were unaware of the patients'
      outcomes. The radiologists recorded the mpMRI features using the Prostate Imaging
      Reporting and Data System (PI-RADS) guidelines. The overall likelihood of the
      presence of significant prostate cancer was also determined using the Likert and
      PI-RADS, version 2 (v2), scores. Univariate and multivariate analyses, receiver
      operating characteristic curves, and Kaplan-Meier survival curves were calculated
      for the mpMRI features with respect to patient withdrawal from the AS program and
      failure-free survival (FFS). The interobserver agreement was also evaluated.
      RESULTS: At a median follow-up time of 31 months (range, 6-80 months), 84
      patients (62.2%) were participating in the AS program. In 2 multivariate models,
      the variables significantly associated with outcomes for both readers were the
      index lesion size (hazard ratio [HR], 2.34 and 3.13, respectively) and overall PI
      RADS, v2, score (HR, 2.51 and 3.21, respectively). The interobserver agreement
      was higher for the overall Likert and PI-RADS, v2, scores. CONCLUSION: Overall,
      the PI-RADS, v2, score and index lesion size were strongly associated with FFS.
      Overall, the Likert and PI-RADS, v2, scoring systems have been confirmed to be
      useful, although further improvements are needed.

PMID- 29198640
TI  - Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing
      Hormone-Releasing Hormone Agonist Therapy.
AB  - BACKGROUND: Serum testosterone measurement is recommended to assess the efficacy
      of androgen deprivation therapy (ADT) and to diagnose castration resistance in
      patients with prostate cancer (PCa). Currently, the accepted castrate level of
      serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass
      spectrometry (LC MSMS) is the appropriate method to measure testosterone,
      especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are
      used in clinical laboratories, despite their lack of accuracy and
      reproducibility, because they are automatable, fast, sensitive, and inexpensive.
      MATERIALS AND METHODS: We compared serum testosterone levels measured using LC
      MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing
      hormone (LHRH) agonist therapy. RESULTS: The median serum testosterone level was
      14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6
      ng/dL) with CLIA (P < .001). The serum testosterone levels, measured using LC
      MSMS, were < 20 ng/dL in 83 patients (65.9%), 20 to 50 ng/dL in 40 (31.7%), and >
      50 ng/dL in 3 patients (2.4%). These ranges were found in 34 (27%), 72 (57.1%),
      and 20 (15.9%) patients when testosterone was measured using CLIA (P < .001). The
      castrate level of serum testosterone using LC MSMS and CLIA was 39.8 ng/dL (95%
      confidence interval [CI], 37.1-43.4 ng/dL) and 66.5 ng/dL (95% CI, 62.3-71.2
      ng/dL), respectively. CONCLUSION: We found that CLIA overestimated the
      testosterone levels in PCa patients undergoing LHRH agonist therapy. Thus, the
      castration level was incorrectly considered inadequate with CLIA in almost 15% of
      patients. The true castration level of serum testosterone using an appropriate
      method is < 50 ng/dL.

PMID- 29198641
TI  - Hemodialysis Self-management Intervention Randomized Trial (HED-SMART): A
      Practical Low-Intensity Intervention to Improve Adherence and Clinical Markers in
      Patients Receiving Hemodialysis.
AB  - BACKGROUND: Poor adherence to treatment is common in hemodialysis patients.
      However, effective interventions for adherence in this population are lacking.
      Small studies of behavioral interventions have yielded improvements, but clinical
      effectiveness and long-term effects are unclear. STUDY DESIGN: Multicenter
      parallel (1:1) design, blinded cluster-randomized controlled trial. SETTING &
      PARTICIPANTS: Patients undergoing maintenance hemodialysis enrolled in 14
      dialysis centers. INTERVENTION: Dialysis shifts of eligible patients were
      randomly assigned to either an interactive and targeted self-management training
      program (HED-SMART; intervention; n=134) or usual care (control; n=101). HED
      SMART, developed using the principles of problem solving and social learning
      theory, was delivered in a group format by health care professionals over 4
      sessions. OUTCOMES & MEASUREMENTS: Serum potassium and phosphate concentrations,
      interdialytic weight gains (IDWGs), self-reported adherence, and self-management
      skills at 1 week, 3 months, and 9 months postintervention. RESULTS: 235
      participants were enrolled in the study (response rate, 44.2%), and 82.1%
      completed the protocol. IDWG was significantly lowered across all 3 assessments
      relative to baseline (P<0.001) among patients randomly assigned to HED-SMART. In
      contrast, IDWG in controls showed no change except at 3 months, when it worsened
      significantly. Improvements in mineral markers were noted in the HED-SMART arm at
      3 months (P<0.001) and in potassium concentrations (P<0.001) at 9 months.
      Phosphate concentrations improved in HED-SMART at 3 months (P=0.03), but these
      effects were not maintained at 9 months postintervention. Significant differences
      between the arms were found for the secondary outcomes of self-reported
      adherence, self-management skills, and self-efficacy at all time points.
      LIMITATIONS: Low proportion of patients with diabetes. CONCLUSIONS: HED-SMART
      provides an effective and practical model for improving health in hemodialysis
      patients. The observed improvements in clinical markers and self-report
      adherence, if maintained at the longer follow-up, could significantly reduce end
      stage renal disease-related complications. Given the feasibility of this kind of
      program, it has strong potential for supplementing usual care. TRIAL
      REGISTRATION: Registered at ISRCTN with study number ISRCTN31434033.

PMID- 29198642
TI  - Caring for Undocumented Immigrants With Kidney Disease.
AB  - The care of dialysis-dependent undocumented immigrants exemplifies a problem at
      the crux of 2 US national agendas: immigration and health care reform.
      Undocumented immigrants represent 3% of the US population and 27% of the
      uninsured, and an estimated 6,500 individuals are dialysis dependent. With no
      uniform national policy, an estimated 30% to 50% of these individuals receive
      treatment only in life-threatening situations (emergent dialysis). Since 2005,
      about 400 undocumented immigrants have received a kidney transplant (>70%
      living). Although the Affordable Care Act specifically excluded noncitizens, its
      policies have indirectly allowed more than 200 individuals to purchase insurance
      from a health insurance exchange and transition from emergent to thrice-weekly
      hemodialysis. Under the Trump administration, uncertainties with health care
      plans, threats of deportation, and rescinding of policies such as sanctuary city
      status are bound to result in unforeseen challenges for this vulnerable
      population. Global variation in the care accessible to migrants, refugees,
      undocumented immigrants, and asylum seekers argues for the need for a framework
      to transform advocacy into public policy to improve the lives of patients with
      kidney disease worldwide. Access to nonemergent dialysis is humane and cost
      effective; it deserves to be espoused and advocated by leading medical
      organizations.

PMID- 29198643
TI  - Validity of a Risk Prediction Equation for CKD After 10 Years of Follow-up in a
      Japanese Population: The Ibaraki Prefectural Health Study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an important health problem for which
      risk equations have been developed for Western populations. This study aimed to
      develop and validate a risk prediction equation for CKD in a Japanese population.
      STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The study
      included 135,007 participants who completed an annual health checkup in 1993 to
      1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD
      (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow
      up information was available from health checkups 10 years after the initial
      evaluation. We used data from 40,963 women and 17,892 men in the northern region
      of the prefecture for the development of risk prediction equations and 53,042
      women and 23,110 men in the southern region for external validation. PREDICTORS:
      Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria,
      hematuria, hypertension, diabetes mellitus, smoking, and drinking. OUTCOME:
      Occurrence of CKD (defined as eGFR<60mL/min/1.73m2 and/or proteinuria [2+ or 3+]
      by dipstick). ANALYTICAL APPROACH: Logistic regression analysis to estimate risk
      for CKD stratified by sex. RESULTS: During follow-up, 7,500 cases of CKD
      developed in the northern region and 8,964, in the southern region. Older age,
      proteinuria (1+), higher systolic blood pressure, medication for hypertension,
      and current smoking were associated with increased risk for CKD in both sexes,
      whereas higher eGFR and daily alcohol intake were associated with lower risk. C
      statistics of risk estimation equations for CKD at 10 years were >0.8 for both
      the development and external validation populations, and discrimination of the
      risk estimation was fairly good in women and men. LIMITATIONS: Fluctuations in
      variables were not evaluated because the study used annual health checkups. This
      study excluded a large number of people for whom a 10-year health checkup was not
      available. CONCLUSIONS: Estimations of risk for CKD after 10 years of follow-up
      in a general Japanese population can be achieved with a high level of validity.

PMID- 29198644
TI  - The diagnostic usefulness of the negative electroretinogram.
AB  - The definition of the negative response of the full field electroretinogram is
      the presence of a b-wave with less amplitude than the a-wave (b/a ratio<1) in the
      combined response of cones and rods. The presence of this pattern reflects an
      alteration in the bipolar cells, the Muller cells, or in the transmission of the
      stimulus from the photoreceptors to the bipolar cells, with preserved
      photoreceptor function. This finding can be seen bilaterally and symmetrically in
      different hereditary conditions, such as congenital stationary night blindness,
      juvenile X-linked retinoschisis, and Duchenne and Becker muscular dystrophies. On
      the other hand, it can also be found unilaterally (or asymmetrically) in acquired
      pathologies, such as some types of immuno-mediated retinitis (Birdshot
      retinochoroiditis), autoimmune retinopathies, cancer/melanoma associated
      retinopathy, or retinal toxicity. The objective of this review is to summarise
      the characteristics of the pathologies in which this finding can be observed, in
      order to highlight its usefulness in the differential diagnosis of retinal
      conditions.

PMID- 29198645
TI  - Let's not twist and spin-doctor our articles.

PMID- 29198646
TI  - Salvage surgery for recurrence of laryngeal and hypopharyngeal squamous cell
      carcinoma: A retrospective study from 2005 to 2013.
AB  - OBJECTIVES: Salvage surgery is the gold-standard treatment for locoregional
      recurrence of laryngeal and hypopharyngeal cancer following radiation therapy.
      Imperfect oncologic and functional results, however, require patient selection.
      The main objective of the present study was to determine preoperative factors for
      survival. Secondary objectives were to study 5-year overall and disease-free
      survival, general and locoregional complications, and functional results in terms
      of feeding and tracheotomy closure. PATIENTS AND METHOD: A retrospective
      multicenter study included 52 patients treated by salvage surgery for recurrence
      of laryngeal or hypopharyngeal squamous cell carcinoma after radiation therapy
      between 2005 and 2013. RESULTS: Factors associated with improved 3-year overall
      survival on univariate analysis comprised laryngeal primary (P=0.001), laryngeal
      recurrence (P=0.026), rT1, rT2 or rT3 rather than rT4 tumor (P=0.007), previous
      chemotherapy (P=0.036), and neck dissection during salvage surgery (P=0.005), the
      last of these being confirmed on multivariate analysis. Five-year overall
      survival was 36.0% (range, 27.6-44.4%), for a median 23.04 months (95% CI, 19.44
      26.64). Five-year disease-free survival was 23.5% (range, 16.0-31.0%), for a
      median 8.04 months (95% CI, 2.04-14.04). CONCLUSION: Salvage surgery for
      laryngeal or hypopharyngeal cancer is difficult, and survival is not good.
      Laryngeal primary and recurrence location, moderate tumor volume and extension
      (<T4), prior chemotherapy and neck dissection during salvage surgery were
      associated with better overall and disease-free survival, which should enable
      better patient selection.

PMID- 29198647
TI  - Isolation functional characterization of allatotropin receptor from the cotton
      bollworm, Helicoverpa armigera.
AB  - Insect allatotropin (AT) plays multi-functions including regulation of juvenile
      hormone synthesis, growth, development and reproduction. In the present study,
      the full-length cDNA encoding the AT receptor was cloned from the brain of
      Helicoverpa armigera (Helar-ATR). The ORF of Helar-ATR exhibited the
      characteristic seven transmembrane domains of the G protein-coupled receptor
      (GPCR) and was close to the ATR of Manduca sexta in the phylogenetic tree. The
      Helar-ATR expressed in vertebrate cell lines can be activated by Helar-AT and
      each Helar-ATL in a dose-responsive manner, in the following order: Helar-ATLI >
      Helar-ATLII > Helar-AT > Helar-ATLIII. Helar-ATLI and Helar-ATLII represented the
      functional ligands to Helar-ATR in vitro, while Helar-AT and Helar-ATLIII behaved
      as partial agonists. The in vitro functional analysis suggested that the Helar
      ATR signal was mainly coupled with elevated levels of Ca2+ and independent of
      cAMP levels. Helar-ATR mRNA in larvae showed the highest level in the brain,
      followed by the thorax ganglion, abdomen ganglion, fat body and midgut. Helar-ATR
      mRNA levels in the complex of the brain-thoracic-abdomen ganglion on the 2nd day
      of the larval stage and during later pupal stages were observed to be relatively
      higher than in the wandering and early pupal stages.

PMID- 29198648
TI  - Advancing the role of the pharmacy technician: A systematic review.
AB  - OBJECTIVES: To summarize the findings of a literature search on advancing the
      role of pharmacy technicians, including the types of training identified and the
      potential costs and benefits to both the technician and the pharmacy. DATA
      SOURCES: A literature search of Scopus, Embase, and Medline was conducted on
      January 11, 2017. STUDY SELECTION: Original research, research reports, case
      studies, or association reports were included for review. Articles were
      considered to be relevant based on identification of an advanced pharmacy
      technician role or addressing additional training/education for technician
      functions. DATA EXTRACTION: A standard data extraction form was used to collect
      study authors, article title, year published, journal title, study design, brief
      description of methods, primary outcome measures, advanced technician roles
      identified, additional education or training addressed, and additional costs and
      benefits identified in each article. RESULTS: A total of 33 articles were
      included for full review and data extraction. Study design varied, with 17 (52%)
      quantitative, 1 (3%) qualitative, 5 (15%) mixed-method, and 10 (30%) case study
      designs. Seventeen (52%) of the studies included were published after 2006. The
      mechanism of training was primarily through supervised on-the-job training,
      allowing technicians to assume administrative-based positions that facilitated a
      pharmacist-led clinical service, with either the pharmacist or the pharmacy
      receiving the greatest benefits. CONCLUSION: Although the literature supports
      technicians performing advanced roles in the pharmacy, resulting in either
      improved patient outcomes or opportunities for pharmacists to engage in
      additional clinical services, the benefits to the technician were primarily
      indirect, such as an increase in job satisfaction or a more desirable work
      schedule. If a technician is to take on additional roles that require completion
      of a formalized training or educational program, benefits that are more tangible
      may help to inspire technicians to pursue these roles.

PMID- 29198649
TI  - ?

PMID- 29198650
TI  - End-in-Sight: Cell Polarization by the Polygamic Organizer PopZ.
AB  - Understanding how asymmetries in cellular constituents are achieved and how such
      positional information directs the construction of structures in a nonrandom
      fashion is a fundamental problem in cell biology. The recent identification of
      determinants that self-assemble into macromolecular complexes at the bacterial
      cell pole provides new insight into the underlying organizational principles in
      bacterial cells. Specifically, polarity studies in host-associated or free-living
      alpha-proteobacteria, a lineage of Gram-negative (diderm) bacteria, reveals that
      functional and cytological mono- and bipolarity is often conferred by the
      multivalent polar organizer PopZ, originally identified as a component of a polar
      chromosome anchor in the cell cycle model system Caulobacter crescentus. PopZ
      dependent polarization appears to be widespread and also functional in obligate
      intracellular pathogens. Here, we discuss how PopZ polarization and the
      establishment of polar complexes occurs, and we detail the physiological roles of
      these complexes.

PMID- 29198651
TI  - Foreword.

PMID- 29198652
TI  - Lorraine Racusen and Kim Solez Awarded the Gold Medal of the Catalan Transplant
      Society.
AB  - In March 2017, a joint meeting between The Catalan Society of Transplantation and
      the Banff Foundation was held at the University of Barcelona. This was an
      opportunity for the Catalan Society of Transplantation to recognize the crucial
      contributions to transplant pathology made by Lorraine Racusen and Kim Solez, who
      created and actively contributed to the development of the International Banff
      Classification System. The ceremony of the Gold Medal took place on March 31 at
      the University of Barcelona; it consisted of a presentation of the contributions
      of Lorraine Racusen and Kim Solez to the development of transplant pathology. In
      this article, the presentation of these awardees with the Gold Medal of the
      Catalan Society of Transplantation is summarized.

PMID- 29198653
TI  - Acceptance of Gold Medal From the Catalan Society of Transplantation by Drs.
      Lorraine Racusen and Kim Solez - With Remarks on the Banff Meeting Spirit.
AB  - The awarding of the gold medal from the Catalan Society of Transplantation to the
      organizers of the Banff Transplant Pathology meetings is an opportunity to
      acknowledge gratitude to all the people who have helped make these meetings a
      success over the past 26 years. Other large organizations have given up consensus
      conferences, but the Banff consensus process is thriving. It is unusual for any
      organization to have the same leadership for 26 years. It has only worked for the
      Banff meetings because the leadership was flexible and able to change with the
      times. People have often talked about the "special Banff spirit." This year's
      meeting gave us the opportunity to examine this spirit in detail by analyzing how
      the meeting consensus sessions and social events functioned. The meeting has
      never used expert facilitators, but instead has employed experts within the
      transplant pathology community to moderate discussions. The size of the working
      sessions is important; they have usually been less than 150 people, which is
      within "Dunbar's number," meaning that in gatherings of that size one can have
      empathetic feeling for all the people there. In larger gatherings one loses that
      "we are all in this together" feeling and people begin thinking "us" versus
      "them" thoughts. For "unknown" young people the ability to easily talk to well
      known leaders in the field is rewarding and keeps them coming back for more time
      after time. Images of the social events do not suggest any sort of hierarchy;
      everyone interacts with everyone else.

PMID- 29198654
TI  - Evaluation of Frozen and Paraffin Sections Using the Maryland Aggregate Pathology
      Index Score in Donor Kidney Biopsy Specimens of a Brazilian Cohort.
AB  - The Maryland aggregate pathology index (MAPI) score is an important tool
      developed to help pathologists in evaluating potential organs for
      transplantation. It is based on analysis of five variables (present or absent):
      arteriolar hyalinosis (4 points), periglomerular fibrosis (2 points), arterial
      wall-lumen ratio superior to 0.5 (2 points), global glomerulosclerosis in more
      than 15% of glomeruli (2 points), and interstitial scar (3 points). Kidneys with
      a MAPI score >7 points are considered inadequate for donation. This study aimed
      to evaluate pathology agreement between frozen sections (FS) and paraffin
      sections (PS) using the MAPI score in a cohort of 262 biopsy specimens obtained
      at the General Hospital of Fortaleza, Brazil. We performed a retrospective review
      of pathological reports of FS (signed out by an on-call pathologist) and their
      corresponding PS (authorized by a specialist in renal pathology). Agreement was
      calculated using the Kappa test. Kappa values ranging from 0.29 to 0.51 were
      obtained when MAPI parameters were separately evaluated. When the score was used,
      the coefficient was 0.59. Fourteen of 262 kidneys were classified as inadequate
      for donation using PS and 8 cases were diagnosed using FS. There were no
      differences between wedge-shaped and filiform samples, apart from the mean number
      of glomeruli. Discordant cases had no statistical difference from concordant ones
      when clinical and macroscopic pathological parameters were analyzed. The MAPI
      score can be useful to minimize disagreements between FS and PS, but more effort
      should be made to standardize criteria and enable pathologists to recognize
      chronic lesions in FS samples.

PMID- 29198655
TI  - Clinical and Pathological Analyses of Cases of Acute Vascular Rejection After
      Kidney Transplantation.
AB  - BACKGROUND: We performed a clinical and pathological analysis of cases of acute
      vascular rejection (AVR), characterized by intimal arteritis and transmural
      arteritis (Banff v score) after kidney transplantation, in an attempt to clarify
      the mechanisms underlying the development and prognostic significance of AVR.
      METHODS: AVR (Banff score: v >0) was diagnosed in 31 renal allograft biopsy
      specimens (BS) obtained from 31 renal transplant patients receiving follow-up
      care at the Department of Urology, Tokyo Women's Medical University, between
      January 2010 and April 2016. RESULTS: AVR was diagnosed at a median of 124.6 days
      after transplantation. Among the 31 BS showing evidence of AVR, AVR was mild (v1
      in Banff's classification) in 25 cases, moderate (v2) in 6, and severe (v3) in
      none. We classified the 31 BS with evidence of AVR by their overall
      histopathological features as follows: isolated v lesions were observed in 6 BS,
      acute antibody-mediated rejection (AAMR) in 7, acute T-cell-mediated rejection
      (ATCMR) in 12, and both ATCR and AAMR in 6. Loss of the renal allograft occurred
      during the observation period in 3 patients, and, of the remaining cases with
      functioning grafts, deterioration of renal allograft function after biopsy
      occurred in only 2 patients. CONCLUSIONS: The results of our study suggest that
      ATCMR contributes to AVR in 40% to 60% of cases, AAMR in 20% to 40% of cases, and
      isolated v lesions in 20% of cases. The prognosis of the patient with the graft
      that had AVR was relatively good under the present immunosuppression protocol and
      current anti-rejection therapies.

PMID- 29198656
TI  - Long-Term Outcomes of Kidney Transplant Recipients With Primary Idiopathic Focal
      Segmental Glomerulosclerosis.
AB  - BACKGROUND: Few data exist on recurrence rates, treatment response, and long-term
      outcomes in kidney transplant recipients (KTR) with primary focal segmental
      glomerulosclerosis (FSGS). METHODS: This retrospective, observational study
      included 1218 consecutive KTR during 2002 to 2016. All patients with primary
      idiopathic FSGS were identified through application of strict diagnostic
      criteria. Outcomes were followed over an average of 70.4 months. RESULTS: We
      identified 48 KTR (3.9%) with primary FSGS. Seven-year death-censored graft
      survival rate was 81% (primary FSGS) versus 85% (control) (P = .297). Eighteen
      KTR had FSGS recurrence (predicted incidence, 50% after 7 years). Seven-year
      death-censored graft survival rate in KTR with FSGS recurrence was significantly
      worse than in FSGS KTR without recurrence (63% versus 96%, P = .010). In the case
      of FSGS recurrence, a multi-modal treatment approach was applied, including
      plasma exchange (PE) (100% of patients), intravenous cyclosporine (50%),
      rituximab (61%), and the "Multiple Target Treatment" (39%). The median number of
      PE sessions was 27. Proteinuria decreased significantly and persistently during
      the course of treatment. Complete remission of FSGS was observed in 7 patients
      (39%); another 7 patients (39%) had partial remission (PE dependence was observed
      in 4 patients [22%]). Four patients (22%) with FSGS recurrence had early graft
      loss (<6 months after transplant) despite all treatment efforts. CONCLUSIONS: In
      KTR with primary FSGS, a high proportion of recurrence occurred, and recurrence
      was associated with significantly worse death-censored graft survival rates.
      However, a multi-modal treatment approach led to improvement of proteinuria and
      full or partial remission in most patients. Importantly, overall death-censored
      graft survival rate in KTR with primary FSGS was comparable with that in the
      control group.

PMID- 29198657
TI  - Association of Brain-Dead Donors' Terminal Inflammation With Delayed Graft
      Function in Kidney Transplant Recipients.
AB  - BACKGROUND: Systemic inflammation affects kidney function in a wide range of
      diseases. Even in kidney transplant recipients, higher levels of C-reactive
      protein (CRP) are invariably associated with both worse short- and long-term
      graft outcomes. However, little is known about systemic inflammation in kidney
      donors and, notably, brain death causes a strong systemic inflammatory response.
      OBJECTIVE: To analyze the role of systemic inflammation of brain-dead donors on
      short-term kidney graft outcomes (ie, delayed graft function [DGF], defined as
      the need of dialysis during the first week after transplantation). MATERIALS AND
      METHODS: Retrospective analysis of clinical and biochemical characteristics of
      all brain-dead kidney donors generated in the Hospital Clinic of Barcelona in the
      2006 to 2015 period (n = 194). Donors who were tested for CRP in the 24 hours
      before BD declaration were included (n = 97, 50% of initial population). Clinical
      and biochemical features of their respective recipients (n = 165) were analyzed,
      comparing recipients who developed DGF (n = 30) with recipients who did not (n =
      135). RESULTS: Donors whose recipients later developed DGF had much higher CRP
      values (10.58 [5.1-18.21] vs 4.81 [1.42-12.2] mg/dL, P = .025). Other
      characteristics associated with the development of DGF were renal biopsy score
      and recipient dialysis vintage (P = .025 and P = .002, respectively). In logistic
      regression analysis, PCR maintained significance in the non-expanded criteria
      donor (ECD) group (odds ratio [OR], 1.102; P = .027), but it lost significance in
      the ECD group (P = .67). CONCLUSIONS: Terminal donor CRP was associated with DGF
      in kidney transplant recipients and proved to be mostly significant in younger
      donors.

PMID- 29198658
TI  - Immunologic Long-term Outcomes of Living-Related Kidney Transplantations
      Depending on the Donor-Recipient Relationship.
AB  - BACKGROUND: The aim of this study is to analyze the long-term immunologic
      outcomes of living-related kidney transplantations depending on the donor
      recipient relationship. METHODS: This retrospective single-center study included
      adult kidney transplant recipients (KTR) transplanted between 2000 and 2014.
      Among 1117 KTRs, 178 patients (15.9%) received living-related donations. Those
      patients were further categorized according to the donor-recipient relationship:
      65 transplantations between siblings, 39 father-to-child (F-t-C) and 74 mother-to
      child (M-t-C) donations. Allograft biopsies were performed for clinically
      suspected rejections. Data analysis included patient and graft survival, biopsy
      proven rejections (T-cell mediated [TCMR] or antibody mediated) and development
      of de novo donor-specific antibody. Outcome data were assessed over a period of a
      maximum 14 years. RESULTS: There was no significant difference between the groups
      (F-t-C, M-t-C, and siblings) with regard to HLA-mismatches, prior kidney
      transplantations, time on dialysis, and cold ischemia time. Among KTRs with
      related donors, the type of relationship had no significant influence on graft
      survival. F-t-C and M-t-C pairs showed comparable incidences of TCMR at 7 years
      post-transplantation, both significantly exceeding the rate in sibling-to-sibling
      pairs (26.2% and 26.8% vs 10%, respectively; P = .043). A multivariate Cox
      regression analysis adjusted for recipient age, donor age, and HLA (A, B, DR)
      mismatches identified both M-t-C- and F-t-C-donations as important independent
      risk factors for TCMR (hazard ratio: 8.13; P < .001 and hazard ratio: 8.09; P =
      .001, respectively). There was no significant difference between the groups
      concerning the incidence of antibody-mediated rejection and de novo donor
      specific antibody. CONCLUSION: Our results indicate that parent-to-child kidney
      donation is an independent risk factor for TCMR.

PMID- 29198659
TI  - Incidence of Infectious Disease and Malignancies After Rituximab Therapy in
      Kidney Transplant Recipients: Results From a Cohort in Germany.
AB  - BACKGROUND: Rituximab is frequently used in solid organ transplantation off
      label, especially in patients with renal allografts. Few data are available on
      the safety aspects of solid organ transplant recipients receiving rituximab.
      There is a knowledge gap on long-term follow-up data, in particular on infectious
      complications. PATIENTS AND METHODS: A retrospective observational registry study
      (German Registry on Autoimmune Diseases) comprising a total of 681 patients was
      conducted. The data of 63 adult kidney transplant recipients who received
      rituximab between 2006 and 2013 were used in this analysis. RESULTS: Median
      follow-up was 42 (1-109) months. At least 1 severe infection occurred in 57% of
      patients. The median time between the first rituximab infusion and the first
      infection was 4 (1-48) months. Of the overall 88 infections, 74 were severe
      bacterial infections, 5 were severe viral infections, 3 were severe fungal
      infections, 2 were combined severe bacterial and fungal infections, and 4 were
      combined severe viral, fungal and bacterial infections. Seven patients died
      during the observational period, 2 of them due to infectious complications. In
      the observational period, 1 case of squamous cell carcinoma but no other
      malignancies were observed. CONCLUSION: Consistent with previous data, a high
      incidence of infections was observed after rituximab treatment in kidney
      transplant recipients. Most infections occurred within 6 months after rituximab
      initiation. With more than 3 years of follow-up, we were able to document a low
      incidence of secondary malignancies after rituximab with only 1 case in our
      cohort.

PMID- 29198660
TI  - Utility of Oxford Classification in Post-Transplant Immunoglobulin A Nephropathy.
AB  - BACKGROUND: With increasing graft survival, post-transplant immunoglobulin A
      nephropathy (IgAN) has emerged as an important cause of chronic graft dysfunction
      in renal allograft recipients. We studied the clinico-pathological features of
      post-transplant IgAN regardless of the primary disease. The aim was to study the
      usefulness of the Oxford classification in predicting survival. METHODS:
      Indication graft biopsy specimens (n = 915) were received during a 10-year
      period; 27 biopsy specimens from 22 patients were diagnosed as IgAN. RESULTS:
      Post-transplant IgAN was seen in 2.6% of biopsy specimens. Mean time to
      occurrence was 71.6 +/- 47.6 months (range, 6.8 months to 16 years), occurring
      most commonly 4 to 8 years after transplant. Associated rejection was present in
      4 biopsies; 72.7% (16/22), 91% (20/22), and 31.8% (7/22) presented with rise in
      serum creatinine, proteinuria, and hematuria, respectively. Four (21%) patients
      had nephrotic range proteinuria. Mesangial hypercelullarity (M1), endocapillary
      hypercelullarity (E1), segmental glomerulosclerosis (S1), and tubulo-interstitial
      fibrosis (T1-2) was present in 36.6%, 22.7%, 54.5%, and 31.8% biopsies,
      respectively. The most frequent Haas class was III (n = 7; 29.1%), followed by
      classes IV and I (n = 5; 20.8% each). The 2- and 5-year graft survival rates were
      75% and 56%, respectively. High serum creatinine, low estimated glomerular
      filtration rate, E1 and T lesions, and degree of interstitial inflammation
      predicted graft survival. Interestingly, percentage (>25%) of segmentally
      sclerosed glomeruli and not S1 correlated with graft outcome. CONCLUSIONS: The
      Oxford MEST scheme is useful in predicting graft survival in post-transplant
      IgAN. The degree of interstitial inflammation is also an important feature for
      determining graft outcomes in post-transplant IgAN.

PMID- 29198661
TI  - Prolonged Low-Dose Prophylaxis With Valganciclovir in Cytomegalovirus-Negative
      Recipients of Kidney Transplants From Cytomegalovirus-Positive Donors Allows
      Seroconversion and Prevents Cytomegalovirus Disease.
AB  - BACKGROUND: Cytomegalovirus-negative recipients of kidneys from cytomegalovirus
      (CMV)-positive donors (D+/R-) are at high risk to develop severe clinical
      manifestations of CMV disease. Long-term data about incidence and timing of CMV
      seroconversion, CMV disease, and the influence of prolonged valganciclovir
      prophylaxis on the clinical course of CMV infection are missing. METHODS: We
      conducted a retrospective long-term study of 89 consecutive CMV D+/R- kidney
      transplant recipients transplanted between 2003 and 2012. All recipients received
      valganciclovir prophylaxis after transplantation (median 187 [126-261] days) with
      a median dose of 213 (181-338) mg/d. Long-term outcome was assessed over a
      maximum of 10 years post-transplant. RESULTS: During follow-up (median 62 months)
      60 of 89 (67%) patients had CMV seroconversion, and 29 of 89 (33%) developed
      symptomatic CMV disease. In addition, in 38 of the 60 (63%), seroconversion
      occurred during prophylaxis (median 154 days post-transplant), and in 22
      patients, after the end of prophylaxis (median 320 days after transplantation).
      Baseline characteristics of the 2 groups did not differ significantly.
      Seroconversion during prophylaxis vs seroconversion after the end of prophylaxis
      was associated with significantly lower incidence of CMV disease (34% vs 73%, P =
      .007), less severe CMV disease (16% vs 64%, P < .001), and fewer organ
      manifestations (26% vs 64%, P = .006). The risk of CMV disease was limited to the
      first 475 days after transplantation. Valganciclovir resistance occurred in just
      1 case (1%). CONCLUSIONS: Prolonged prophylaxis with low-dose valganciclovir
      allowed CMV seroconversion during prophylaxis in a high proportion of D+/R-
      patients. Seroconversion occurred after a median of 154 days and was associated
      with significantly lower incidence of CMV disease, less severe CMV disease, and
      fewer CMV complications.

PMID- 29198662
TI  - Epidemiology and Risk Factors for Cancer After Lung Transplantation.
AB  - Cancer is the third most common cause of death among lung transplant (LT)
      recipients who survive for more than 1 year. The purpose of this study was to
      analyze the incidence and risk factors for cancer after LT in a Spanish cohort.
      The epidemiology and risk factors for cancer were retrospectively analyzed in LT
      recipients from 2 cities in Spain, Madrid and Barcelona. Of the 1353 LT patients
      initially included in the study, 125 (9.2%) developed cancer after a mean of 3.7
      years. This frequency was 5-fold higher than in the general population. The most
      prevalent tumors were skin cancer (32%), lymphoproliferative disease (18%), and
      lung cancer (16.5%). In 4 patients, lung cancer was diagnosed on the day of the
      operation. The risk of cancer increased with age >55 year (hazard ratio [HR] 2.89
      [1.64-5.09]; P < .001), in men (HR 2.8 [1.4-5.6]; P = .004), and in heavy smokers
      (>20 pack-years) (HR 2.94 [1.64-5.27]; P < .001). Other factors such as sun
      exposure were not found to be risk factors. In conclusion, prevalence of cancer
      is high in LT recipients in a Mediterranean country. Skin tumors,
      lymphoproliferative disease, and lung cancer are the most prevalent cancers. Age,
      male sex, and smoking were the main risk factors for cancer in this population.

PMID- 29198663
TI  - Determination of the Culture Time Point to Induce Corneal Epithelial
      Differentiation in Induced Pluripotent Stem Cells.
AB  - BACKGROUND: Limbal stem cells (LSC) are progenitor cells in the ocular surface
      that renew the corneal epithelium. Limbal stem cell deficiency usually induces
      blindness through the loss of corneal transparency, and bilateral cases do not an
      accurate treatment because of the lack of an autologous source of stem cells.
      METHODS: Induced pluripotent stem cells (iPSC) are promising for use in cell
      therapy because of their autologous origin and the capability to differentiate
      into corneal epithelial cells. However, there are not standardized protocols to
      achieve a complete corneal epithelial differentiation. We examined the expression
      of several markers in a human episomal iPSC line after an induction period from
      embryoid bodies. RESULTS: Progenitor LSC and corneal epithelial differentiation
      markers, some extracellular matrix protein adhesion molecules, and wingless
      signaling pathway were studied. Overall, LSC progenitor and corneal epithelium
      differentiation markers increased after maintaining cell culture in specific
      conditions for 14 days, whereas pluripotency markers decreased. CONCLUSIONS: Our
      approach indicated that the optimal time point to initiate iPSC differentiation
      into LSC and corneal phenotypes, with the use of specific medium, is from 14 days
      after initial embryoid bodies treatment induction.

PMID- 29198664
TI  - Relatives' Perception After Tissue Donation Experience: Results of a Postdonation
      Phone Survey.
AB  - INTRODUCTION: Postmortem tissue donation (TD) requires the establishment of
      strategies for family approach to clearly explain the characteristics of multi
      tissue donation. In a tertiary university hospital with a long tradition of
      tissue generation, we designed a survey to be applied to tissue donor families to
      evaluate global hospital care, care from Transplant Coordinators (TC), quality
      and content of information given about TD, experience, and motivations after TD
      process. METHODOLOGY: A prospective phone survey of 10 multiple-choice items was
      conducted to all TD relatives that agreed to donate one or more tissues. RESULTS:
      From the 166 calls made to TD relatives, 75 (45%) were answered: 50 were cornea
      donors and 25 were multiple-tissues donors. None of the relatives denied
      participating, the rest were not found. No statistical differences in
      demographical variables were found between both types of TD. The hospital and TC
      care perception, the quality of the given information about the processes of TD,
      the postdonation experiences in terms of procedures, and the impression about
      body appearance for relatives regardless of the type of donation, corneas or
      multiple tissues, were evaluated as good or very good for most of the TD
      relatives. Our study showed that 83% of the family members would agree to donate
      again; 40% of the relatives were surprised to be offered the option to donate;
      10% did not know if they would donate again. Solidarity was the leading reason
      for TD. CONCLUSION: The relatives' perception of care is a critical component of
      the quality evaluation of the TD process. The global evaluation results support
      our strategies for family approach.

PMID- 29198665
TI  - Isolated Crystalloid Podocytopathy With Focal Segmental Glomerulosclerosis in
      Renal Allograft: An Unusual Presentation of Post-Transplant Monoclonal Gammopathy
      of Renal Significance-A Case Report.
AB  - BACKGROUND: Monoclonal gammopathy of renal significance denotes a spectrum of
      hematologic disorders that cause direct or indirect renal damage. CASE
      PRESENTATION: A 51-year-old man had received a living-donor kidney transplant
      from his wife in 2008. He had gradual increased proteinuria 4 years later. His
      renal biopsy results revealed cytoplasmic crystalloid inclusions in the
      podocytes. No crystalloid inclusion was found in other renal cells. Despite that
      immunofluorescent examination failed to show light-chain deposition, the serum
      immuno-electrophoresis revealed monoclonal immunoglobulin-Gkappa. Bone marrow
      biopsy showed interstitial infiltration of plasma cells of approximately 10%. A
      follow-up renal biopsy was performed in 2016. Light microscopy showed focal
      segmental glomerulosclerosis. The immunofluorescent examination remained negative
      for light chain, but kappa-light chain could be demonstrated after antigen
      retrieval. Similar to previous biopsy results, cytoplasmic inclusions were found
      only in podocytes without involving other renal cells. CONCLUSIONS: To the best
      of our knowledge, this is the first report of monoclonal gammopathy of renal
      significance presenting as isolated crystalloid podocytopathy in the allograft
      kidney. The mechanism of preferential podocyte deposition of crystalloid
      immunoglobulin remains unclear. The inherent features of crystalloid
      podocytopathy may mislead the pathologic diagnosis.

PMID- 29198666
TI  - The Pancreas Can Take the Cold: Lower Waitlist Times Through Importation.
AB  - BACKGROUND: Our center has used a strategy of pancreas importation owing to long
      regional waitlist times. Here we assess the clinical outcomes and financial
      considerations of this strategy. METHODS: This was a retrospective observational
      cohort study of patients who received a pancreas transplant at Montefiore Medical
      Center (MMC) from 2014 to 2017 (n = 28). Clinical parameters, including
      hemoglobin A1c and complications, were analyzed. The cohort was compared with
      United Network for Organ Sharing (UNOS) Region 9 with the use of the UNOS/Organ
      Procurement and Transplantation Network database. Cost analysis of length of stay
      (LOS), standard acquisition (SAC) fees, and transportation was performed with the
      use of internal financial data. RESULTS: Pancreas importation resulted in
      significantly shorter simultaneous pancreas kidney transplant waitlist times
      compared with Region 9: 518 days vs 1001 days (P = .038). In addition,
      postoperative complications and 1-year HbA1c did not differ between groups: local
      6.30% vs import 6.17% (P = .87). Patients receiving local pancreata stayed an
      average of 9.2 days compared with 11 days for the import group (P = .36). As
      such, pancreas importation was associated with higher mean charges ($445,968)
      compared with local pancreas recipients ($325,470). CONCLUSIONS: Long waitlist
      times in Region 9 have encouraged our center's adoption of pancreas importation
      to address the needs of our patient population. This practice has resulted in a
      reduction of waitlist times by an average of 483 days. Understandably, centers
      have long been wary of importation owing to perceived risk in clinical outcomes.
      In our single-center experience, we have demonstrated equivalent postoperative
      glucose control and graft survival. Importantly, there does appear to be
      increased costs associated with importation, which are mainly driven by LOS.
      Curiously, importation from regions with lower SAC fees has the potential to
      offset costs related to transportation expenses. Notwithstanding these findings,
      pancreas importation does have the potential to lessen the financial societal
      burden through reduction in waitlist times.

PMID- 29198667
TI  - Donation After Circulatory Arrest in Pancreas Transplantation: A Report of 10
      Cases.
AB  - INTRODUCTION: Transplantation of pancreas allografts procured from donation after
      circulatory death (DCD) remains uncommon. This study reviews a series of pancreas
      transplants at a single center to assess the donor and recipient characteristics
      for DCD pancreas transplant and to compare clinical outcomes. METHODS: DCD
      procurement was performed with a 5-minute wait time from pronouncement of death
      to first incision. In 2 patients, tissue plasminogen activator was infused as a
      thrombolytic during the donor flush. All kidney grafts were placed on pulsatile
      perfusion. RESULTS: There were 606 deceased donor pancreas transplants, 596
      standard donors and 10 DCD donors. Of the 10 DCD transplants, 6 were simultaneous
      pancreas-kidney and 4 were pancreas transplant alone. The average time from
      incision to aortic cannulation was less than 3 minutes. The median total ischemia
      time for the DCD grafts was 5.4 hours, compared with 8.0 hours for standard
      donors (P = .15). Median length of hospital stay was 7 days for both groups, and
      there were no episode of acute cellular rejection in the first year post
      transplant for the DCD group (4.2 % for standard group, P = .65). There was no
      difference in early or late graft survival, with 100% graft survival in the DCD
      group up to 1 year post-transplant. Ten-year Kaplan-Meier analysis shows similar
      graft survival for the 2 groups (P = .92). CONCLUSIONS: These results support the
      routine use of carefully selected DCD pancreas donors. There were no differences
      in graft function, postoperative complications, and early and late graft
      survival.

PMID- 29198668
TI  - A Case of Successful Simultaneous Pancreas-Kidney Transplantation Using the
      Injured Pancreas Graft.
AB  - OBJECTIVE: Graft injuries sometimes occur and may cause complications such as the
      leakage of pancreatic secretions, which is often lethal. We report our experience
      of a case of successful simultaneous pancreas-kidney transplantation using
      injured pancreas graft. PATIENTS AND METHODS: The recipient was a 57-year-old
      woman with type 1 diabetes mellitus, and the donor was a 30-year-old man with a
      brain injury. In the donation, the pancreas parenchyma, splenic artery, and
      gastroduodenal artery were injured iatrogenically. We therefore reconstructed
      these arteries using vessel grafts and then performed simultaneous pancreas
      kidney transplantation. RESULTS: Five days after transplantation, we noted a high
      titer of amylase in the ascites; therefore, we performed an urgent laparotomy.
      The origin of the amylase was the injured pancreatic parenchyma, and continued
      washing and drainage were carried out. We reconstructed the duodenojejunostomy
      using the Roux-en-Y technique to separate the passage of food from the pancreas
      graft to prevent injury to other organs due to exposure to pancreatic secretions.
      Thereafter, we inserted a decompression tube into the anastomosis thorough the
      blind end of the jejunum. Finally, we inserted 3 drainage tubes for lavage.
      Following this procedure, the patient recovered gradually and no longer required
      hemodialysis and insulin therapy. She was discharged from our hospital 56 days
      after transplantation. CONCLUSION: The restoration of the injured graft was
      possible by management of pancreatic secretions and use of the donor's vessel
      grafts. Shortage of donors is a problem throughout the world; thus, it is
      important to use injured grafts for transplantation if possible.

PMID- 29198669
TI  - Broadened Allocation of Pancreas Transplants Across Compatible ABO Blood Types.
AB  - BACKGROUND: Current Organ Procurement and Transplantation Network (OPTN) policy
      restricts certain blood type-compatible simultaneous pancreas and kidney (SPK)
      transplants. Using the Kidney Pancreas Simulated Allocation Model, we examined
      the effects of 5 alternative allocation sequences that allowed all clinically
      compatible ABO transplants. METHODS: The study cohort included kidney (KI), SPK,
      and pancreas alone (PA) candidates waiting for transplant for at least 1 day
      between January 1, 2010, and December 31, 2010 (full cohort), and kidneys and
      pancreata recovered for transplant during the same period. Additionally, because
      the waiting list has shrunk since 2010, the study population was reduced by
      random sampling to match the volume of the 2015 waiting list (reduced cohort).
      RESULTS: Compared with the current allocation sequence, R4 and R5 both showed an
      increase in SPK transplants, a nearly corresponding decrease in KI transplants,
      and virtually no change in PA transplants. Life-years from transplant and median
      years of benefit also increased. The distribution of transplants by blood type
      changed, with more ABO:A, B, and AB transplants performed, and fewer ABO:O across
      all transplant types (KI, SPK, PA), with the relative percent changes largest for
      SPK. DISCUSSION: Broadened ABO compatibility allowances primarily benefitted SPK
      ABO:A and AB candidates. ABO:O candidates saw potentially reduced access to
      transplant. The simulation results suggest that modifying the current allocation
      sequence to incorporate broadened ABO compatibility can result in an increase in
      annual SPK transplants.

PMID- 29198670
TI  - Difficult Situation of Pancreas Transplantation in the Setting of Scarce Organ
      Donation.
AB  - BACKGROUND: Currently, pancreas transplantation has been a promising strategy to
      restore long-term normoglycemia as well as to improve life quality for patients
      with insulin-dependent diabetes mellitus (DM). However, the discrepancy between
      the number of organs needed and the number donated for transplantation is always
      enormous. Under a setting of scarce organ donations, we examined our limited
      experience of pancreas transplantation. METHODS: A retrospective review of
      pancreas transplantations was performed with the use of data from the Taiwan
      Organ Registry and Sharing Center and the Ministry of Health and Welfare.
      Pancreas transplantations in the Organ Transplantation Institute of Chang Gung
      Memorial Hospital also were reviewed. RESULTS: At present, there are 5 medical
      centers approved for pancreas transplantation in Taiwan. Overall, a total of 156
      pancreas transplantations were performed from 2005 to the end of 2016; only 9 of
      them were performed in the Organ Transplantation Institute of Chang Gung Memorial
      Hospital. Although the number of organ donations is rising, pancreas
      transplantation numbers remain low. More than 20 pancreas transplantations were
      performed in 2016, yet there remained a total of 111 patients registered on the
      wait list for pancreas transplantation at the end of this study. Thus the gap
      between organ donation and transplantation is still vast. CONCLUSIONS: With
      continuing improvements in Taiwanese health policies and public education
      regarding organ transplantation, organ donation rates have risen steadily in
      recent years. Moreover, quality control and continuing evolution in organ
      transplantation is crucial to ameliorate the difficult situation of pancreas
      transplantation and other solid organ transplantation in the context of low
      levels of donation.

PMID- 29198671
TI  - Effect of Etanercept Concentration on Human Islet Integrity.
AB  - BACKGROUND: Etanercept is widely used as an antiinflammatory drug to improve
      engraftment after intraportal islet transplantation. In contrast to other
      immunosuppressive agents, very little is known about detrimental effects of
      etanercept on islets. The aim of this pilot study was to define the toxic range
      of etanercept. METHODS: Human islets isolated from 8 donors were cultured for 4-5
      days at 37 degrees C in culture medium supplemented with etanercept at
      concentrations from 2.5 to 40 MUg/mL, corresponding to potential in vivo levels
      within the portal vein. After culture, islet equivalent (IEQ) yield,
      fragmentation index (islet number/IEQ), purity, viability, and stimulated insulin
      release (2 vs 20 mmol/L) were assessed and normalized to islets before culture.
      RESULTS: Yield (73 +/- 8%) and viability (91 +/- 4%) were highest with 5 MUg/mL
      etanercept. Islet loss was evident when etanercept was >=10 MUg/mL (55 +/- 7%; P
      < .05 vs control). Fragmentation (154 +/- 34%; P < .05) was markedly increased
      and viability (81 +/- 4%, P < .05) markedly decreased with etanercept >10 MUg/mL.
      The accumulation of cell debris at concentrations >=20 MUg/mL resulted in a
      significant reduction of islet purity (84 +/- 3%; P < .05). Etanercept did not
      interfere with stimulated insulin secretion at concentrations <=10 MUg/mL. The
      maximum stimulation index was noted at 2.5 MUg/mL (1.8 +/- 0.1). CONCLUSIONS:
      Etanercept is tolerated by isolated human islets at concentrations <10 MUg/mL.
      Our data suggest that the tight range between benefit and toxicity should be
      considered for dosage and administration of etanercept.

PMID- 29198672
TI  - Hypoxia-Induced Damage in Human Islets Is Reduced With the Use of Mesenchymal
      Stem Cell-Preconditioned Medium.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are protective for islets when
      cotransplanted in a hypoxic environment. However, the risk of neoplasia is
      increased when MSCs are transplanted into immunosuppressed patients. This initial
      study aimed to investigate whether the production of protective factors from MSC
      can be stimulated by different culture conditions to benefit human islets
      cultured in hypoxia. METHODS: MSC were isolated from human adipose tissue and
      cultured for 2 days in supplemented Minimum Essential Media alpha (MEMalpha) and
      21% (21%-MEMalpha) or 1% oxygen (1%-MEMalpha). Native MEMalpha served as control.
      After MSC harvesting, cell-depleted media were frozen at -20 degrees C until use
      for human islet culture in 2% oxygen for 72-96 hours before islet
      characterization. Data were normalized to control islets cultured in native
      MEMalpha and 2% oxygen (mean +/- SEM). RESULTS: After culture in 21%- or 1%
      MEMalpha, islet recovery increased to 117 +/- 12% (NS) and 138 +/- 12% (P < .05),
      respectively. Viability did not change after culture in native MEMalpha (59 +/-
      2%), 21%-MEMalpha (59 +/- 3%), or 1%-MEMalpha (61 +/- 3%). Compared with control
      samples, the glucose stimulation index was increased after culture in 21%
      MEMalpha (P < .05) or 1%-MEMalpha (P < .05). Overall survival was higher in 1%
      MEMalpha (143 +/- 14%) than in 21%-MEMalpha (119 +/- 14%; NS) or native MEMalpha
      (P < .05). CONCLUSIONS: This study demonstrates that MSC-preconditioned MEMalpha
      increases survival and in vitro function of hypoxic human islets. These findings
      indicate that hypoxic MSCs seem to produce factors that improve survival of
      islets suffering from hypoxia.

PMID- 29198673
TI  - Pain Control, Glucose Control, and Quality of Life in Patients With Chronic
      Pancreatitis After Total Pancreatectomy With Islet Autotransplantation: A
      Preliminary Report.
AB  - BACKGROUND: Total pancreatectomy (TP) is offered as a last treatment option for
      pain relief in patients with chronic pancreatitis. Concurrent islets
      autotransplantation (TP-IAT) may improve glucose control. METHODS: We analyzed
      results in 20 recent patients who underwent TP-IAT at The University of Chicago.
      The median observation period was 28 months (2-38). Data were collected
      prospectively then analyzed retrospectively. RESULTS: The number of patients
      requiring opioids daily for pain control decreased from 16 (80%) prior to surgery
      to 2 (13%) 1 year after, with only 1 (6.5%) patient experiencing persistent
      phantom pancreatic pain. Opioid requirements decreased from a median 56.3 (0-240)
      morphine equivalent dose to 5 (0-130) on day 75 and to 0 (0-30) at 1-year follow
      up. Five patients (25%) completely stopped insulin support prior to day 75 while
      maintaining hemoglobin A1c of 5.9% (5-6.3). Eight (53%) patients were insulin
      free at 1 year with A1c of 6% (5.5-6.8) and a similar rate persisted in next 2
      years. For the remaining patients, the more islet function that was preserved,
      the less insulin they required and A1c was closer to optimal. Quality of Life
      (QoL) measured by SF36 Physical (PCS) and Mental (MCS) Component Score improved
      on day 75 (P < .001) and maintained improvement later on. Both PCS and MCS
      improved regardless of whether patient requires insulin support or not.
      CONCLUSIONS: Improvements of QoL with pain resolution and good glucose control
      can be achieved after TP-IAT in properly selected patients with CP and
      intractable pain, regardless of patient insulin support status.

PMID- 29198674
TI  - External Validation of the Newly Developed BETA-2 Scoring System for Pancreatic
      Islet Graft Function Assessment.
AB  - BACKGROUND: BETA-2 score using a single fasting blood sample was developed to
      estimate beta-cell function after islet transplantation (ITx) and was validated
      internally by a high ITx volume center (Edmonton). The goal was to validate BETA
      2 externally, in our center. METHODS: Areas under receiver operating
      characteristic curves (AUROCs) were obtained to see if beta score or BETA-2 would
      better detect insulin independence and glucose intolerance. RESULTS: We analyzed
      values from 48 mixed meal tolerance tests (MMTTs) in 4 ITx recipients with a long
      term follow-up to 140 months (LT group) and from 54 MMTTs in 13 short-term group
      patients (ST group). AUROC for no need for insulin support was 0.776 (95%
      confidence interval [CI] 0.539-1, P = .02) and 0.922 (95% CI 0.848-0.996, P <
      .001) for beta score and 0.79 (95% CI 0.596-0.983, P = .003) and 0.941 (95% CI
      0.86-1, P < .001) for BETA-2, in LT and ST groups, respectively, and did not
      differ significantly. In LT group BETA-2 score >= 13.03 predicted no need for
      insulin supplementation with sensitivity of 98%, specificity of 50%, positive
      predictive value (PPV) of 93%, and negative predictive value (NPV) of 75%. In ST
      group the optimal cutoff was >=13.63 with sensitivity of 92% and specificity,
      PPV, and NPV 82% to 95%. For the detection of glucose intolerance BETA-2 cutoffs
      were <19.43 in LT group and <17.23 in ST group with sensitivity > 76% and
      specificity, PPV, and NPV > 80% in both groups. CONCLUSION: BETA-2 score was
      successfully validated externally and is a practical tool allowing for frequent
      and reliable assessments of islet graft function based on a single fasting blood
      sample.

PMID- 29198675
TI  - Retroperitoneal Pancreas Transplantation With the Use of Duodenal Drainage via
      "Button Technique": First Clinical Practice (Case Report).
AB  - The persistent relative high incidence of duodenum-associated surgical
      complications significantly reduces pancreas grafts' (PG) and recipients'
      survival rates. A 31-year-old female patient underwent retroperitoneal pancreas
      transplantation with the use of PG exocrine drainage into the recipient's
      duodenum via the "button technique" approach. An uncomplicated postoperative
      period with satisfactory function of both transplants (pancreas and kidney) was
      noted. This was the 1st time ever that the transplantation was performed with the
      use of retroperitoneal placement of the pancreas transplant and duodenal drainage
      via the "button technique" approach. It is possible that the absence of the
      duodenal stump in the donor's transplant has a number of benefits in the
      postoperative period, which can be confirmed during the follow-up observations.

PMID- 29198676
TI  - Case Report: Primary De Novo Sarcoma In Transplant Pancreas Allograft.
AB  - BACKGROUND: The majority of malignancies after transplantation appear to be
      virally mediated and of recipient origin. Donor-derived neoplasms occur early,
      whereas recipient-origin tumors typically occur many years after transplantation.
      Sarcomas are a relatively rare form of cancer. The etiology of sarcomas remains
      largely unknown, although some are linked to viruses, familial cancer syndromes,
      or therapeutic radiation exposure. Primary sarcomas are extremely rare,
      accounting for <0.1% of all native pancreatic malignancies. The involvement of
      the allograft itself in the tumor is rare. CASE REPORT: A 53-year-old white woman
      (body mass index, 20.1 kg/m2) with a history of type 1 diabetes, chronic kidney
      disease, coronary artery disease, dyslipidemia, and pancreas-alone
      transplantation in 2007 was admitted with small bowel obstruction secondary to a
      mass in the head of the pancreas allograft, for which a laparotomy with allograft
      pancreatectomy was required. Histopathologic exam revealed a stage III high-grade
      unclassified spindle cell sarcoma positive for polyomavirus. After surgery, the
      patient was managed with close monitoring for disease recurrence. Her most recent
      scan was negative for recurrence at postoperative day 489. CONCLUSIONS: We report
      a previously unreported phenomenon of a soft tissue sarcoma arising in a pancreas
      allograft, likely of recipient origin and polyomavirus related. Standard
      treatment for sarcoma is wide excision of the tumor and close monitoring for
      recurrence. Systemic chemotherapy or radiotherapy is usually limited to advanced
      cases. Sarcomas may occur in a pancreas allograft. Allograft pancreatectomy and
      monitoring for recurrence is vital for a good outcome.

PMID- 29198677
TI  - Single Donor-Derived Pseudomonas aeruginosa Pseudoaneurysms in Two Kidney
      Transplant Recipients: A Case Report of Dichotomous Allograft Outcomes.
AB  - Infectious pseudoaneurysm (IPA) is a rare but devastating complication following
      renal transplantation that typically leads to graft loss and occasionally patient
      death. IPAs following kidney transplantation are most often mycotic in etiology,
      but have been sporadically reported to result from Pseudomonas aeruginosa
      infection. These IPAs occur at various anatomic sites, most commonly at the
      vascular anastomosis or iliac artery, and very rarely in the transplanted renal
      artery or hilum. Here we report the occurrence of single donor-derived P
      aeruginosa IPAs in two kidney transplant recipients with divergent allograft
      outcomes. Both recipients manifested Pseudomonas infections and early,
      hemodynamically relevant postoperative hemorrhage as a result of pseudoaneurysm
      rupture. One recipient required allograft nephrectomy during emergent operative
      exploration due to rupture of a pseudoaneurysm at the vascular anastomosis.
      Conversely, the other recipient's allograft was salvaged by endovascular stenting
      of a pseudoaneurysm unusually located in the main donor renal artery. To the best
      of our knowledge, this is the first case of a ruptured IPA occurring in the
      transplanted renal artery with successful allograft salvage via endovascular
      technique. In this report, we discuss details of the two cases, relevant
      literature, and possible clinical implications.

PMID- 29198678
TI  - Successful Diagnosis of Intestinal Mycobacterium avium Complex Infection in a
      Kidney Transplant Recipient Using Nasogastric Aspirate Culture: A Case Report.
AB  - Intestinal Mycobacterium avium complex (MAC) infections are rare and can be
      challenging to diagnose. We describe a case of intestinal MAC infection in a
      kidney transplant recipient with 5 months of unexplained weight loss and
      abdominal pain who developed intestinal obstruction. Esophagoduodenoscopy with
      biopsies was performed but was nondiagnostic. Intestinal MAC was diagnosed via
      nasogastric aspirate culture results. The patient's symptoms rapidly improved
      after initiation of appropriate treatment, but he later died of aspiration
      pneumonia and candidemia.

PMID- 29198679
TI  - Treatment of a Pediatric Case of Severe Hemorrhagic Cystitis: Case Report and
      Review of Literature.
AB  - Hemorrhagic cystitis is one of the complications of allogeneic hematopoietic stem
      cell transplantation. Treatment of hemorrhagic cystitis is difficult, especially
      in pediatric patients. A pediatric case of severe hemorrhagic cystitis after
      hematopoietic stem cell transplantation was treated in our hospital with arterial
      embolization combined with corticosteroid therapy because the conventional
      therapy was invalid for him. After the treatment, hemorrhagic cystitis was cured.
      During follow-up, the patient was in stable condition, with normal urine, blood
      cells returned to normal, bone marrow was in complete remission state, and
      disease-free survival for more than 8 months. Selective bladder arterial embolism
      followed by corticosteroid therapy successfully treated the patient.

PMID- 29198680
TI  - Syndrome of Inappropriate Antidiuretic Hormone Secretion Complicating Systemic
      Nocardiosis in a Renal Transplant Recipient: A Case Report.
AB  - BACKGROUND: Infection by Nocardia species is an uncommon cause of severe clinical
      syndromes, particularly in immunocompromised patients, and solid-organ
      transplantation is the most common underlying condition. The syndrome of
      inappropriate antidiuretic hormone secretion (SIADH) has been described thus far
      in lung and stem cell transplants with systemic nocardiosis. CASE REPORT: We
      report the first case of SIADH in a female elderly renal transplant recipient
      diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was
      managed appropriately, and her immunosuppressive regimen remained unchanged but
      was adjusted at a lower level. The systemic Nocardia infection was successfully
      treated with intravenous administration of trimethoprim-sulfamethoxazole and
      imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total
      of 12 months. CONCLUSIONS: The SIADH syndrome is a recognizable complication of
      Nocardia infection in renal transplant recipients. Prompt identification along
      with proper management and prolonged antimicrobial treatment are essential to
      improve patients' outcome.

PMID- 29198681
TI  - Severe Hyperkalemia Complicating Voriconazole Treatment in a Kidney Transplant
      Recipient With Histoplasmosis: A Case Report.
AB  - Voriconazole is an antifungal agent that is commonly used in immunocompromised
      patients who develop fungal infections. We report a case of severe recurrent
      hyperkalemia that developed after starting voriconazole for the treatment of
      histoplasmosis in a kidney transplant patient who was maintained on tacrolimus
      based immunosuppression. Hyperkalemia developed despite reducing the tacrolimus
      dose to maintain levels in a low therapeutic range. Although interactions between
      azoles and calcineurin inhibitors are widely recognized, this is the 1st report
      describing new-onset hyperkalemia following initiation of voriconazole in a
      kidney transplant patient receiving tacrolimus.

PMID- 29198682
TI  - Case Report: Treatment of Renal Artery Aneurysms by Ex Vivo Renal Artery Aneurysm
      Repair and Transplantation.
AB  - BACKGROUND: Renal artery aneurysms are increasingly being detected incidentally
      during diagnostic imaging using magnetic resonance imaging, computed tomography,
      or angiography performed for evaluation of other diseases. Our understanding of
      their natural history and surgical management has evolved significantly during
      the past two decades. PATIENTS AND METHODS: Three patients with incidentally
      identified renal artery aneurysms have been referred to our renal transplantation
      program in the last 3 years. All three had aneurysms located at renal artery
      branches making endovascular repair challenging and thus underwent hand-assisted
      laparoscopic nephrectomy with ex vivo aneurysmectomy, with heterotopic
      autotransplantation in two cases and allotransplantation in the third case.
      RESULTS: All three cases resulted in successful renal artery aneurysm repair and
      reimplantation and good renal function of the implanted kidney. CONCLUSIONS:
      Laparoscopic nephrectomy with ex vivo aneurysm repair and reimplantation can be a
      successful approach to surgical management, especially in cases where the
      aneurysm involves multiple artery branches and endovascular repair is
      challenging. Given the excellent results with this surgical approach, living and
      deceased donor kidneys with aneurysms should be strongly encouraged if deemed
      reparable.

PMID- 29198683
TI  - Laparoscopic Fixation for Torsion of Transplanted Kidney: A Case Report.
AB  - BACKGROUND: Kidney graft torsion and subsequent acute kidney injury is a rare yet
      potentially devastating complication of intraperitoneal kidney transplant. We
      report a case of this elusive diagnosis and describe kidney salvage by using
      laparoscopic fixation. CASE REPORT: A 49-year-old male patient presented with
      multiple episodes of anuric acute kidney injury 16 months after an uneventful
      combined orthotopic liver and kidney transplantation. After a thorough
      investigation, a diagnosis of kidney torsion was made, and the patient was
      urgently operated. Upon surgery, a complete torsion of a viable kidney was found.
      Laparoscopic fixation was achieved by using an absorbable mesh "pocket." The
      patient has experienced no similar episodes in the subsequent year. CONCLUSIONS:
      Nephrologists and surgeons should be aware of this rare complication. Prompt
      diagnosis and operative repair are crucial to save the graft. Prophylactic
      nephropexy should be considered in all intraperitoneal transplantations.

PMID- 29198684
TI  - Nephrogenic Adenoma Complicating Renal Transplantation: A Case Report and
      Discussion.
AB  - Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract.
      Long considered to be a rare phenomenon, case series from the renal transplant
      population suggest that it may be much more common within this group. Although NA
      is considered to be a lesion with low premalignant potential, hematuria, lower
      urinary tract symptoms, and recurrent urinary tract infections (UTIs) are
      frequently observed in the context of NA. Furthermore, after resection of NA,
      lesion recurrence and persistent symptoms are frequently observed. Here we
      present the case of a 69-year-old male renal transplant recipient with NA and
      associated recurrent UTIs despite cystoscopic resection of the primary lesion.
      This case is illustrative of the clinical impact of NA and the need for ongoing
      work into the development of strategies to manage this problematic phenomenon.

PMID- 29198685
TI  - Thin Glomerular Basement Membrane in a Kidney Transplant of an Alport's Syndrome
      Patient: A Case Report.
AB  - Alport syndrome (AS) and thin basement membrane lesions are caused by various
      mutations in type IV collagen genes. Although AS is considered a rare disease,
      thin basement membrane is a frequent pattern, especially in families with a
      history of persistent hematuria. We report a patient with a diagnosis of AS who
      developed end-stage kidney disease (ESKD) and received a kidney transplant from a
      living unrelated donor. The graft biopsy specimen surprisingly showed a pattern
      of thin basement membranes.

PMID- 29198686
TI  - Orthotopic Kidney Transplantation in an Elderly Patient With Various Severe
      Comorbid Conditions: A Case Report.
AB  - In recent years, the frequency of high-risk kidney transplantations has
      increased. We report a case in which a 72-year-old man with various severe
      comorbidities (prostate cancer, diabetes mellitus, complete atrioventricular
      block, coronary artery stenosis, severe stenosis of the popliteal arteries, and
      severe calcification of the iliac arteries) who received an orthotopic kidney
      transplantation. To prevent the occurrence of acute limb ischemia due to the
      steal phenomenon (caused by the kidney graft), we decided that a heterotopic
      kidney transplantation involving the iliac arteries was not an appropriate
      option. Therefore, as an alternative, left native nephrectomy was performed
      followed by an orthotopic kidney transplantation to the native renal artery and
      renal vein through a left subcostal incision. Postoperative ureteral stenosis
      occurred, and so stent exchange was required every 6 months. Despite the ureteral
      complication, the patient's serum creatinine level was 1.5 mg/dL at 2 years after
      the procedure.

PMID- 29198687
TI  - Takotsubo Cardiomyopathy Resulting in Cardiac Arrest in a Patient Undergoing
      Liver Transplantation.
AB  - Cardiac complications during and after liver transplantation are a common cause
      of death. Although considered to be uncommon, takotsubo cardiomyopathy, which is
      characterized by reversible left ventricular akinesis without coronary artery
      obstruction, is becoming increasingly reported. Herein we have presented a case
      of reversible stress-induced takotsubo cardiomyopathy resulting in cardiac arrest
      in a patient undergoing liver transplantation.

PMID- 29198688
TI  - Hanging Hepato-Atrial Anastomosis in Deceased-Donor Liver Transplantation for
      Budd-Chiari Syndrome With Extensive Vena Cava Obliteration: A Case Report.
AB  - INTRODUCTION: Although outcomes of liver transplantation (LT) have improved as
      the result of progress in surgical procedures, a failure to restore sufficient
      graft outflow may yield fatal consequences including graft dysfunction and even
      graft loss to date. In particular, patients with pre-existing obliterated venous
      drainage, such as those with Budd-Chiari syndrome (BCS), are at high risk of
      having venous complications followed by conventional LT. In selected cases, the
      transplant surgeons are compelled to modify the surgical procedures of LT from
      the conventional procedure. METHODS: We describe an LT performed in a BCS patient
      with complete inferior vena cava (IVC) obstruction. A procedure that we named
      "hanging hepato-atrial anastomosis" was performed, in which 2 major modifications
      were made. One modification was the dissection of the lower inlet of the right
      atrium by use of a trans-abdominal approach and hepato-atrial anastomosis. This
      was performed by exposing the thoracic IVC through a trans-abdominal approach.
      The other modification was the manufacture of a blind pouch from the graft's
      infra-hepatic IVC without anastomosis. RESULTS: Modifications were made possible
      as the result of meticulous examination of the patient's vascular anatomy before
      the operation. Fortunately, the patient had a heavy network of pre-vertebral
      veins that drained blood from the lower extremity and both kidneys to the azygos
      hemi-azygos veins. CONCLUSIONS: We learned that a meticulous assessment of
      vascular anatomy and complete understanding of hemodynamics are the keys to the
      successful LT for BCS in patients with extensive IVC abnormality. Thoracotomy may
      not be necessary to explore thoracic IVC when performing hepato-atrial
      anastomosis in LT for BCS.

PMID- 29198689
TI  - Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia
      During Liver Transplantation: A Case Report.
AB  - Severe hyponatremia can complicate the pretransplantation management of patients
      with decompensated cirrhosis while they await liver transplantation. Before the
      liver transplant, it is critical to correct severe hyponatremia to an appropriate
      level to reduce the risks of perioperative complications such as central pontine
      myelinolysis, cerebral edema, and seizures. Vasopressin receptor antagonists, and
      in particular tolvaptan, offer a therapeutic modality that can correct severe
      refractory hyponatremia in a timely and predictable manner before liver
      transplantation. In this case report, we describe a patient with decompensated
      cirrhosis and severe hyponatremia in whom administration of tolvaptan led to an
      optimal correction of preoperative severe hyponatremia and allowed for successful
      liver transplantation with no associated postoperative complications. In light of
      the increasing pretransplantation disease severity and higher risk of severe
      hyponatremia, the use of tolvaptan in the pretransplant period may gain
      increasing importance as a therapeutic intervention for maintaining
      peritransplant sodium homeostasis.

PMID- 29198690
TI  - Preexisting Cerebral Aspergillosis Successfully Treated After Liver
      Transplantation: A Case Report.
AB  - BACKGROUND: Invasive aspergillosis (IA) is a rare condition that generally
      affects immunosuppressed patients. The mortality of IA is known to be >90% in
      liver transplantation (LT) recipients; the lung is the most commonly affected
      organ, followed by the brain. There have been reports in the literature of
      cerebral aspergillosis (CA) in LT recipients. In all previous reports, CA
      developed after LT. We present the first case (to the best of our knowledge) of
      preexisting CA diagnosed and successfully treated after LT. CASE REPORT: A 59
      year-old male patient underwent emergency deceased-donor LT for alcoholic liver
      cirrhosis. Preoperative imaging showed multiple lesions in both cerebral
      hemispheres, indicative of brain abscess or metastases. Before definitive
      diagnosis of the brain lesion, the deceased-donor LT was performed. On
      postoperative day 15, the patient developed a fever of 38.0 degrees C and drowsy
      mental status. Magnetic resonance imaging showed increased number and size of
      brain abscesses. Stereotactic brain abscess aspiration was performed, and
      pathologic findings revealed aspergillosis. Voriconazole was started immediately.
      The patient improved steadily and was discharged 1 month after initiation of
      voriconazole treatment. CONCLUSIONS: This case is the first report of preexisting
      CA treated successfully after LT. Voriconazole is a potent therapeutic agent of
      CA. When LT is performed with an undiagnosed brain lesion, aggressive diagnostic
      measures are necessary postoperatively. If CA is diagnosed, successful treatment
      may be possible with voriconazole.

PMID- 29198691
TI  - Successful Liver Transplantation From a Donor With a Continuous-Flow Left
      Ventricular Assist Device for 9 Months.
AB  - Organ donor criteria continue to be extended in an attempt to meet growing
      demands. Patients with continuous-flow left ventricular assist devices are one
      group of potential donors being considered. One concern with this group is the
      effect of continuous flow for a prolonged duration, as opposed to normal
      pulsatile flow, on end-organ function. We report the 1st case of a liver
      transplantation from a donor who had a continuous-flow left ventricular assist
      device for 9 months. The recipient was a 69-year-old woman with a history of
      cryptogenic cirrhosis and hepatocellular carcinoma. The transplantation was
      complicated by moderate acute cellular rejection as well as biliary obstruction
      requiring sphincterotomy and stent placement. After management of those
      complications, the patient's liver function tests returned to normal values and
      remained stable at her 6-month post-transplantation follow-up. This case shows
      that organ transplantation from a donor with a continuous-flow left ventricular
      assist device for a prolonged period can be performed successfully.

PMID- 29198692
TI  - Successful Recombinant Thrombomodulin Treatment for Thrombotic Microangiopathy
      After Liver Transplantation: A Case Report.
AB  - Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe
      complication after liver transplantation. In contrast to other thrombotic
      microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old
      male patient with liver cirrhosis due to hepatitis C underwent split liver
      transplantation from a deceased donor. His clinical course was without
      complication until 4 days after transplantation, when he experienced impaired
      consciousness, hemolytic anemia with fragmented erythrocytes, and marked
      thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was
      administered for 4 days. The patient's clinical symptoms and laboratory data
      rapidly improved. He has been followed up for 6 months and has not shown any
      complications. The pathogenesis of TA-TMA is endothelial damage in the
      vasculature. Recombinant thrombomodulin, an endothelial cell-protecting agent, is
      a promising new therapeutic choice for TA-TMA after liver transplantation.

PMID- 29198693
TI  - Impact of Ethylene Glycol Toxicity on Donor Organ Viability: A Case Report.
AB  - Using kidneys from deceased donors whose demise was secondary to ethylene glycol
      (EG) toxicity requires considerable thought and planning. The exact impact that
      kidneys from these donors could have is unclear. The shortage of viable organs
      and growing wait list mortality should lead us to consider these allografts as
      potential life-saving transplants. Because it is crucial for the transplant
      community to use every available allograft, we need to develop processes that
      optimize each possible scenario. This article is a discussion of the viability of
      kidneys from a donor with EG-induced brain death and a proposed algorithm for
      encouraging the use of renal allografts after EG toxicity.

PMID- 29198694
TI  - Reversible Cerebral Vasoconstriction Syndrome After Heart Transplantation: A Case
      Report.
AB  - BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a transient
      cerebrovascular disorder putatively caused by some immunosuppressive agents. CASE
      REPORT: We recently encountered a 47-year-old female patient diagnosed with
      dilated cardiomyopathy who developed RCVS after heart transplantation. A triple
      drug regimen consisting of tacrolimus, mycophenolate mofetil, and a
      corticosteroid was started after surgery. On postoperative day (POD) 11, the
      patient developed a severe headache, although computed tomography of the head
      demonstrated no signs of hemorrhage or infarction. At first, both a painkiller
      and migraine drugs were regularly administered to the patient. On POD 21,
      however, she developed an unbearable headache with a visual field defect and mild
      hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain
      revealed a cerebral infarction in the left occipital lobe with diffuse
      vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis
      of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was
      discontinued. In its place, two doses of basiliximab followed by everolimus, both
      of which are alternatives for tacrolimus, were given. The corticosteroid dose was
      also increased. Furthermore, to release vasoconstriction, both verapamil and
      diltiazem were administered. On POD 27, cerebrovascular constrictions were shown
      to be relieved on brain MRI and the patient's neurological symptoms subsequently
      almost completely diminished. CONCLUSION: RCVS should always be considered as a
      cause of headache in heart transplant recipients because tacrolimus, an
      immunosuppressive agent, may trigger RCVS. This will allow rapid intervention
      that is essential for avoiding irreversible neurological deficits.

PMID- 29198695
TI  - "Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration
      After Acute Rejection of Small-Bowel Transplantation: A Case Report.
AB  - Intestinal failure characterized by inadequate maintenance of nutrition via
      normal intestinal function comprises a group of disorders with many different
      causes. If parenteral nutrition dependency develops, which is associated with
      higher mortality and complications, it is considered for intestine
      transplantation. However, the graft failure rate is not low, and acute cellular
      rejection is one of the most important reasons for graft failure. As a result,
      early identification of rejection and timely modification of anti-rejection
      medications have been considered to be associated with better graft and patient
      survival rates. The diagnostic gold standard for rejection is mainly based on
      histology, but hours of delay by pathology may occur. Some researchers
      investigated the association of endoscopic images with graft rejection to provide
      timely diagnosis. In this study, we present the first case report with
      characteristic features under magnifying endoscopy with a narrow-band imaging
      system to predict epithelial regeneration and improvement of graft rejection in a
      patient with small-bowel transplantation.

PMID- 29198696
TI  - Erratum.

PMID- 29198697
TI  - Indurated Nodule on the Upper Lip.

PMID- 29198698
TI  - Successful Intravenous Immunoglobulin Treatment in Pediatric Severe DRESS
      Syndrome.
AB  - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a
      rare, potentially life-threatening delayed drug-induced hypersensitivity
      reaction. The most frequently reported drugs causing DRESS are aromatic
      antiepileptic agents. Prompt withdrawal of the offending drug and administering
      systemic corticosteroids is the most widely accepted and used treatment. The
      treatment of severe DRESS not responsive to systemic corticosteroids is
      uncertain. OBJECTIVE: The objective of this study was to describe a case series
      of pediatric patients with DRESS who were treated successfully with intravenous
      immunoglobulins (IVIGs). METHODS: A retrospective review of all children
      hospitalized in a tertiary care children's hospital with severe DRESS syndrome
      who received IVIG in addition to offending drug withdrawal and systemic
      corticosteroids during 1999-2017 is performed. RESULTS: Seven severe DRESS
      patients (4 males, age: 9.5 +/- 5.7 years) are described. The offending drugs
      were antiepileptics in all but one case. Clinical findings included fever, rash,
      lymphadenopathy, dyspnea, anasarca, and hepatic involvement. After IVIG treatment
      (total dosage: 1-2 g/kg), fever resolved within a median time of 1 (range, 0-5)
      day, rash disappeared after 6.3 +/- 1.6 days, and liver enzymes substantially
      improved after 3.8 +/- 1.6 days. Patients were discharged 6.1 +/- 2.7 days after
      IVIG commencement. There was no mortality. CONCLUSION: The addition of IVIG in
      DRESS syndrome resistant to regular drug withdrawal and systemic corticosteroid
      therapy may hasten disease recovery.

PMID- 29198699
TI  - Activation of PKB/Akt and p44/42 by mechanical stretch utilizes desmosomal
      structures and the keratin filament.
AB  - BACKGROUND: Mechanical stress is an ubiquitous challenge of human cells with
      fundamental impact on cell physiology. Previous studies have shown that
      stretching promotes signalling cascades involved in proliferation and tissue
      enlargement. OBJECTIVE: The present study is dedicated to learn more about
      cellular structures contributing to perception and signal transmission of cell
      stretch. In particular, we hypothesized that desmosmal contacts and the adjacent
      keratin filament build an intercellular matrix providing information about the
      mechanical load. METHODS: Epidermal cells with different keratin equipment were
      seeded on flexible silicon dishes and stretched. As read out parameter the
      activation of PKB/Akt and p44/42 was monitored by Western blotting. Likewise
      desomosomal contacts were manipulated by depletion or addition of calcium.
      Moreover, desmoglein 3 and desmocollin 3 were blocked by either specific
      antibodies or siRNA. RESULTS: It was found that the omission of calcium from the
      medium, a necessary cofactor for desmosomal cadherins, inhibited stretch mediated
      activation of PKB/Akt and p44/42. The relevance of desmosomes in this context was
      further substantiated by experiments using a desmoglein 3 blocking antibody
      (AK23) and siRNA against desmocollin 3. Moreover, disruption of the keratin
      filament by sodium orthovanadate also abrogates PKB/Akt and p44/42 activation in
      response to stretch. Likewise, KEB-7 keratinocytes harbouring a mutation in the
      keratin 14 gene and genetically modified keratinocytes devoid of any keratin show
      an altered signalling after stretch indicating the relevance of the keratin
      filament in this context. CONCLUSION: Besides their important role in cell
      architecture our results identify desmosomes and keratins as mechanosensing
      structures.

PMID- 29198700
TI  - Probing transport of fosfomycin through substrate specific OprO and OprP from
      Pseudomonas aeruginosa.
AB  - Increasing antimicrobial drug resistance is a global threat especially with
      respect to Gram-negative bacteria. The low permeability of the bacterial outer
      cell wall has been identified as an important bottleneck that prevents a
      sufficient antibacterial effect to be achieved at low doses of the antibiotics.
      In particular, the outer membrane permeability for negatively charged molecules
      of the clinical important ESKAPE bacterium Pseudomonas aeruginosa is determined
      by the low conductance porins OprO and OprP Here we show that the alternative
      phosphonic-acid antibiotic fosfomycin is highly permeable through the OprO and
      OprP channels. For this, we applied an electrophysiological zero-current assay
      using concentration gradients of fosfomycin under tri-ionic conditions to
      quantify flux of fosfomycin through OprO and OprP. Our analyzes show that OprO,
      and to a lesser degree OprP, have unexpected very high permeability to
      fosfomycin, so the antibiotic should be a potentially excellent alternative
      choice for the control of Pseudomonas aeruginosa infections.

PMID- 29198701
TI  - Down-regulation of lncRNA MEG3 promotes hypoxia-induced human pulmonary artery
      smooth muscle cell proliferation and migration via repressing PTEN by sponging
      miR-21.
AB  - Hypoxia-induced pulmonary hypertension is a life-threatening disease arising from
      a progressive increase in pulmonary vascular resistance, irreversible pulmonary
      vascular remodeling and resulting in right ventricular failure. Recent studies
      suggested that pulmonary artery smooth muscle cell proliferation and migration
      played an important role in the pathogenesis of hypoxia-induced pulmonary
      hypertension. However, the mechanisms of hypoxia-induced pulmonary hypertension
      are complicated and largely unclear. In this study, we discovered that lncRNA
      MEG3 was down-regulated in human pulmonary artery smooth muscle cell in hypoxia,
      and inhibition of MEG3 promoted the cell proliferation and cell migration in both
      normal and hypoxia condition. Further study demonstrated that MEG3 exerted its
      function via regulation of miR-21 expression in both normal and hypoxia
      condition. In addition, we displayed the modulation of PTEN by miR-21 and their
      role in hypoxia. Ultimately, our study illustrated that MEG3 exerts its role via
      miR-21/PTEN axis in human pulmonary artery smooth muscle cell under both normal
      and hypoxia conditions.

PMID- 29198702
TI  - Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar
      epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.
AB  - Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged
      hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells
      and eventually leads to development of bronchopulmonary dysplasia (BPD). Many
      studies have shown that hydrogen has a protective effect in a variety of cells.
      However, the mechanisms by which hydrogen rescues cells from damage due to
      oxidative stress in BPD remains to be fully elucidated. This study sought to
      evaluate the effects of hydrogen on hyperoxia-induced lung injury and to
      investigate the underlying mechanism. Primary type II alveolar epithelial cells
      (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95%
      oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt
      inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay
      and flow cytometry (FCM), respectively. Gene and protein expression were detected
      by quantitative polymerase chain reaction (q-PCR) and western blot analysis.
      Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1
      and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which
      induced proliferation restriction and apoptosis of AECIIs. These effects of
      hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective
      effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results
      indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by
      inhibiting apoptosis factors and promoting the expression of anti-apoptosis
      factors. These effects were associated with activation of the PI3K/Akt/FoxO3a
      pathway.

PMID- 29198703
TI  - Impaired autophagy promotes bile acid-induced hepatic injury and accumulation of
      ubiquitinated proteins.
AB  - Chronic exposure to hydrophobic bile acids such as chenodeoxycholic acid (CDCA)
      and cholic acid (CA) in the liver during cholestasis causes hepatotoxicity and
      inflammatory response. However, the detailed mechanisms regarding the role of
      autophagy in cholestatic hepatotoxicity remain largely unknown. Here we
      determined autophagic clearance in livers of bile duct-ligated mice, in which
      bile acids accumulate, and in human hepatoma HepG2 cells treated with CDCA and
      CA. The accumulation of bile acids caused defective autophagic clearance, shown
      by the accumulation of insoluble p62 and ubiquitinated proteins and cell death
      accompanied by caspase-3 processing. Hepatocytes exposed to bile acids also
      showed the accumulation of autophagosomes via suppressed autophagy flux.
      Treatment of CDCA markedly suppressed Beclin-1 expression, which exhibits a
      higher cytotoxicity than CA. Moreover, pharmacological or genetic inhibition of
      autophagy enhanced bile acid-induced cell death. Finally, in vivo, bile duct
      ligation led to aberrant accumulation of p62 and ubiquitinated proteins in the
      liver. Our data demonstrate that inhibited autophagy is an essential component of
      liver injury during cholestasis.

PMID- 29198704
TI  - Ischemic flap survival improvement by composition-selective fat grafting with
      novel adipose tissue derived product - stromal vascular fraction gel.
AB  - BACKGROUND: Flap necrosis due to insufficient blood supply is a common
      postoperative complication in random pattern flaps. Stem cell therapies have
      emerged as promising biologics for tissue ischemia. A novel fat derived product,
      stromal vascular fraction gel (SVF-gel), can be prepared with lipoaspirate
      through simple mechanical processing, removing only the lipid content. SVF-gel
      enriches adipose-derived stem cells and potentially beneficial for flap necrosis.
      METHODS: Nude mice ischemic flaps were treated with human SVF-gel, stromal
      vascular fraction (SVF) cell suspension or saline (n = 10). They were injected to
      the flap recipient beds, and necrosis and vascularization was assessed on
      postoperative day 14. We harvested the necrosis-free distal to evaluated skin
      healthiness and neovasculogenesis by Masson's trichrome stain and
      immunofluorescence, etc. Pro-angiogenic factors were assessed with tissue qRT
      PCR. Finally, we traced the grafted human tissue with immunofluorescence.
      RESULTS: SVF-gel-treated flaps have the smallest necrotic zones (22.05% +/-
      0.0438) compared with the saline controls (53.78% +/- 0.1412) or SVF-treated ones
      (35.54% +/- 0.0850, p = 0.039). Numerous functional musculocutaneous perforators
      were developed around SVF-gel grafts. The SVF-gel-treated skin had the best fat
      restoration (231.3 +/- 48.1 MUm) among three groups (F = 10.83, p = 0.0102) while
      saline-treated flap distal appeared fibrotic. SVF-gel-treated flaps also had ~43%
      more CD31 + capillaries (p = 0.0152) with ~3 folds more gene expression of
      angiogenic cytokines of VEGF and bFGF (p = 0.0310 and 0.0303, respectively) than
      saline-treated controls. Furthermore, we found hSVF-gel cells (hGolgi+) had
      directly engrafted as vessel component (alpha-smooth muscle actin, alpha-SMA+) to
      the flap. CONCLUSION: Adipose cellular matrix enhanced flap neovascularization
      partly by direct incorporation, improved flap survival and fat restoration. The
      composition-selective fat grafting with SVF-gel demonstrated efficacy comparable
      with stem cell therapy and is especially valuable for clinical translation.

PMID- 29198705
TI  - Tilapia and human CLIC2 structures are highly conserved.
AB  - Chloride intracellular channels (CLICs) exist in soluble and membrane bound
      forms. We have determined the crystal structure of soluble Clic2 from the
      euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia
      and human CLIC2 with other CLICs shows that these proteins are highly conserved.
      We have also compared the expression levels of clic2 in selected osmoregulatory
      organs of tilapia, acclimated to freshwater, seawater and hypersaline water.
      Structural conservation of vertebrate CLICs implies that they might play
      conserved roles. Also, tissue-specific responsiveness of clic2 suggests that it
      might be involved in iono-osmoregulation under extreme conditions in tilapia.

PMID- 29198706
TI  - Structural insight into the substrate specificity of acyl-CoA oxidase1 from
      Yarrowia lipolytica for short-chain dicarboxylyl-CoAs.
AB  - Acyl-CoA oxidase (ACOX) plays an important role in fatty acid degradation. The
      enzyme catalyzes the first reaction in peroxisomal fatty acid beta-oxidation by
      reducing acyl-CoA to 2-trans-enoyl-CoA. The yeast Yarrowia lipolytica is able to
      utilize fatty acids, fats, and oil as carbon sources to produce valuable
      bioproducts. We determined the crystal structure of ACOX1 from Y. lipolytica
      (YlACOX1) at a resolution of 2.5 A. YlACOX1 forms a homodimer, and the monomeric
      structure is composed of four domains, the Nalpha, Nbeta, Calpha1, and Calpha2.
      The FAD cofactor is bound at the dimerization interface between the Nbeta- and
      Calpha1-domains. The substrate-binding tunnel formed by the interface between the
      Nalpha-, Nbeta-, and Calpha1-domains is located proximal to FAD. Amino acid and
      structural comparisons of YlACOX1 with other ACOXs show that the substrate
      binding pocket of YlACOX1 is much smaller than that of the medium- or long-chain
      ACOXs but is rather similar to that of the short-chain ACOXs. Moreover, the
      hydrophilicity of residues constituting the end region of the substrate-binding
      pocket in YlACOX1 is quite similar to those in the short-chain ACOXs but
      different from those of the medium- or long-chain ACOXs. These observations
      provide structural insights how YlACOX1 prefers short-chain dicarboxylyl-CoAs as
      a substrate.

PMID- 29198707
TI  - Impaired vagus function in rats suppresses bile acid synthesis in the liver by
      disrupting tight junctions and activating Fxr-Fgf15 signaling in the intestine.
AB  - Bile acids (BAs) circulate between the liver and intestine, and regulate the
      homeostasis of glucose, lipid, and energy. Recent studies demonstrated an
      essential role of BAs in neurological diseases, suggesting an interaction between
      BAs and the nervous system. In the present study, we showed that impaired vagus
      function in rats induced by vagotomy resulted in an increase in bile flow without
      causing liver injury. The concentrations of unconjugated and glycine-conjugated
      BAs were increased in both serum and bile of rats after vagotomy, which was due
      to impaired tight junctions and thus increased passive absorption of BAs in the
      intestine. Vagotomy markedly suppressed the expression of the rate-limiting BA
      synthetic enzyme Cyp7a1, which was not due to activation of Fxr-Shp signaling in
      the liver, but due to activation of Fxr-Fgf15 signaling in the intestine.
      Furthermore, vagotomy produced a BA profile in the bile favorable for Fxr
      activation by decreasing tauro-beta-muricholic acid, a natural Fxr antagonist,
      and increasing glyco-chenodeoxycholic acid, a natural Fxr agonist. In summary,
      the present study provides the first comprehensive analysis of the critical role
      of the vagus nerve in regulating BA metabolism and signaling pathway.

PMID- 29198708
TI  - Knockdown of laminin alpha5 stimulates intestinal cell differentiation.
AB  - Interactions between cells and the extracellular matrix regulate a wide range of
      cell processes such as proliferation and differentiation. Laminins are major
      components of the basement membrane that actively participate in most biological
      functions via their interactions with a variety of specific cell receptors. The
      alpha5-containing laminins (LAMA5) are one of the three main types of laminins
      identified at the epithelial basal lamina in the adult intestine. The aim of the
      present study was to investigate the role of alpha5-containing laminins on
      intestinal cell proliferation and differentiation. Using an shRNA targeting
      approach, the effects of knocking down the expression of LAMA5 were investigated
      in the enterocytic-like Caco-2/15 cell line, a well-characterized model for
      intestinal cell differentiation. Surprisingly, the abolition of the laminin
      alpha5 chain resulted in a drastic increase in the differentiation marker sucrase
      isomaltase which was correctly expressed at the apical pole of the cells as
      observed by indirect immunofluorescence. Transient increases of
      dipeptidylpeptidase IV, villin, CDX2, HNF-1alpha, HNF-4alpha and transepithelial
      resistance as well as an apparent redistribution of the junctional components ZO
      1 and E-cadherin were also observed at early stages of differentiation but no
      specific effect was observed on cell proliferation as evaluated by BrdU
      incorporation. Taken together, these data suggest that alpha5-containing laminins
      repress intestinal differentiation in its early stages.

PMID- 29198709
TI  - Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction.
AB  - Cell-in-cell structure is prevalent in human cancer, and associated with several
      specific pathophysiological phenomena. Although cell membrane adhesion molecules
      were found critical for cell-in-cell formation, the roles of other membrane
      components, such as lipids, remain to be explored. In this study, we attempted to
      investigate the effects of cholesterol and phospholipids on the formation of cell
      in-cell structures by utilizing liposome as a vector. We found that Lipofectamine
      2000, the reagent commonly used for routine transfection, could significantly
      reduce entotic cell-in-cell formation in a cell-specific manner, which is
      correlated with suppressed actomyosin contraction as indicated by reduced beta
      actin expression and myosin light chain phosphorylation. The influence on cell-in
      cell formation was likely dictated by specific liposome components as some
      liposomes affected cell-in-cell formation while some others didn't. Screening on
      a limited number of lipids, the major components of liposome, identified
      phosphatidylethanolamine (PE), stearamide (SA), lysophosphatidic acid (LPA) and
      cholesterol (CHOL) as the inhibitors of cell-in-cell formation. Importantly,
      cholesterol treatment significantly inhibited myosin light chain phosphorylation,
      which resembles the effect of Lipofectamine-2000, suggesting cholesterol might be
      partially responsible for liposomes' effects on cell-in-cell formation. Together,
      our findings supporting a role of membrane lipids and cholesterol in cell-in-cell
      formation probably via regulating actomyosin contraction.

PMID- 29198710
TI  - The protective effect of orally administered redox nanoparticle on intestinal
      ischemia-reperfusion injury in mice.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (I-R) injury is a serious abdominal
      condition leading to multiple organ failure with high mortality. However, no
      reliable treatment is available. A redox nanoparticle (RNPO) was recently
      developed, and its efficacy for several intestinal inflammatory conditions has
      been reported. To this end, the aim of this study was to investigate the
      therapeutic effects of RNPO on intestinal I-R injury in mice. METHODS: Ischemia
      was induced in the small intestine of C57BL/6 mice by occluding the superior
      mesenteric artery for 45 min under anesthesia followed by reperfusion for 4 h.
      Mice were orally administered the vehicle or RNPO 1 h before ischemia.
      Inflammatory markers such as histological findings, thiobarbituric acid (TBA)
      reactive substances as an index of lipid peroxidation, myeloperoxidase (MPO)
      activity as an index of neutrophil infiltration, and expression of pro
      inflammatory cytokine mRNA in the intestinal mucosa were assessed. RESULTS:
      Induction of I-R caused a significant increase in inflammatory markers
      (histological scores, TBA-reactive substances, MPO activity, and expression of
      keratinocyte chemoattractant mRNA). These changes were significantly attenuated
      in RNPO-treated mice as compared to vehicle-treated mice. CONCLUSION: Orally
      administered RNPO attenuated intestinal I-R injury in mice in association with
      reductions in neutrophil infiltration and lipid peroxidation, suggesting the
      possibly potential of RNPO as a therapeutic agent for intestinal I-R injury.

PMID- 29198711
TI  - Effects of connective tissue growth factor (CTGF/CCN2) on condylar chondrocyte
      proliferation, migration, maturation, differentiation and signalling pathway.
AB  - CCN2, also known as connective tissue growth factor (CTGF), is a 38 kDa cysteine
      rich extracellular matrix protein that regulates a sequence of cellular functions
      and participates in multiple complex biological processes, such as chondrogenesis
      and osteogenesis. In the present study, we provided the first evidence describing
      the physiological role of CCN2 in condylar chondrocyte proliferation, migration,
      maturation and differentiation. CCN2 was widely expressed throughout the whole
      layers of condylar cartilage and predominantly distributed in the proliferative
      zone. Recombinant CCN2 promoted the proliferation, migration, proteoglycan
      synthesis and differentiation capacity of isolated condylar chondrocytes. The
      stimulatory effect of CCN2 on chondrocyte proliferation was associated with the
      activation of phosphatidylinositol 3-kinase/Akt signalling pathway. The blocking
      of this pathway by its inhibitor LY294002 impaired the proliferative effect of
      CCN2 on chondrocytes. These results suggested a novel physiological role of CCN2
      in the development of condylar cartilage.

PMID- 29198712
TI  - FBW7 targets KLF10 for ubiquitin-dependent degradation.
AB  - FBW7, a key component of SCFFBW7 E3 ubiquitin ligase, targets various proteins
      for degradation via the conserved Cdc4 phosphodegron (CPD) in substrates. In this
      study, we report that KLF10 is degraded by FBW7 via a conserved CPD. Through
      systematic analysis of the degradation of KLF transcription factors by FBW7, we
      identified KLF10 as a novel degradation target of FBW7. Ectopic expression of
      FBW7 markedly promoted the degradation of KLF10 while knockdown of endogenous
      FBW7 increased the protein levels of KLF10. In addition, simultaneous mutations
      of both threonine 82 (T82) and serine 86 (S86) significantly reduced the FBW7
      mediated KLF10 degradation. Moreover, KLF10 containing a conserved putative CPD
      (TPPXSP) from amino acids 82 to 87, directly interacted with WD40 domain of FBW7
      in a phosphorylation-dependent manner. Importantly, FBW7 could reverse the KLF10
      mediated inhibition of Smad7 activity. Thus, our study uncovers a novel
      regulatory mechanism underlying which KLF10 stability and its biological function
      are mediated by FBW7.

PMID- 29198713
TI  - Long-term immunological effects of Japanese cedar pollen-based subcutaneous
      immunotherapy.

PMID- 29198714
TI  - Chertsey Outcome Score for Trauma: Development and validation of a new unifying
      patient reported outcome measure for orthopaedic trauma.
AB  - PURPOSE: Lately there is an increasing tendency of using Patient Reported Outcome
      Measures (PROMs) as a final indicator of the outcome of many surgical treatments
      in orthopaedics and in other medical specialties. Currently there are many
      outcome scores in orthopaedics and most of them are site specific. In the
      contrary there is a lack of trauma specific outcome scores. METHODS: We have
      designed a new PROM especially for orthopaedic trauma patients, in order to
      measure in what extent the patients manage to return to their pre-injury state.
      This score uses as baseline the pre-injury status of the patient and has the aim
      to determine the percentage of rehabilitation after treatment for any injury.
      RESULTS: A total of 60 Chertsey Outcome Score for Trauma (COST) questionnaires
      were gathered in our outpatients department. The participants were 57% male (aged
      46.81 years +/- 18.5 years) and the questionnaires collected at mean 10 months
      post-injury. A Cronbach's Alpha value of 0.89 was identified for the whole
      construct. The three dimensions of the scale had good internal consistency as
      well (Cronbach's Alpha test values 0.74, 0.84 and 0.81 for symptoms, function and
      mental status respectively). Strong/moderate correlation (Spearman's Rho test
      0.43-0.65) was observed between the respective physical/mental dimensions of the
      COST and SF-12v2 questionnaires. CONCLUSION: There is a need among the
      orthopaedic trauma society for a specific PROM of trauma. COST is a useful and
      easy to use tool for every trauma surgeon.

PMID- 29198715
TI  - Predicting mortality, hospital length of stay and need for surgery in pediatric
      trauma patients.
AB  - PURPOSE: Pediatric trauma is one of the major health problems around the world
      which threats the life of children. The survival of injured children depends upon
      appropriate care, accurate triage and effective emergent surgery. The objective
      of this study was to determine the predictive values of injury severity score
      (ISS), new injury severity score (NISS) and revised trauma score (RTS) on
      children's mortality, hospitalization and need for surgery. METHODS: In this
      study, records of trauma patients under 15 years old transported from a trauma
      scene to emergency department of Poursina hospital from 2010 to 2011 were
      included. Statistical analysis was applied to determine the ISS, NISS and RTS
      ability in predicting the outcomes of interest. RESULTS: There were 588 records
      in hospital registry system. The mean age of the patients was (7.3 +/- 3.8)
      years, and 62.1% (n = 365) of patients were male. RTS was the more ability score
      to predict mortality with an area under curve (AUC) of 0.99 (95% CI, 0.99-1). In
      the hospital length of stay (LOS), ISS was best predictor for both the hospital
      LOS with AUC of 0.72 (95% CI, 0.67-0.76) and need for surgical surgery with AUC
      of 0.94 (95% CI, 0.90-0.98). CONCLUSION: RTS as a physiological scoring system
      has a higher predicting AUC value in predicting mortality. The anatomic scoring
      systems of ISS and NISS have good performance in predicting of hospital LOS and
      need for surgery outcomes.

PMID- 29198716
TI  - Non-anatomic fixation for longstanding traumatic pubic diastasis using a bone
      graft: A report of two cases.
AB  - The incidence of internal fixation failure of symphysis diastasis varies from 6%
      to 75%. Hardware breakage or migration and symphysis disruption recurrence are
      often asymptomatic and only in a few cases reoperation is required. This report
      describes the managements of two cases after failed internal fixation and
      neglected traumatic symphysis diastasis when it was technically impossible to
      achieve anatomical reduction of the anterior pelvic ring. Internal fixation and a
      bone graft for the symphysis without anatomical reposition were performed. Both
      of the patients achieved good results and had no complaints of pain during daily
      activities. Restoration of the anatomy should not be the aim in treating
      recurrence of the symphysis diastasis after failed fixation. The aim of the
      surgery was static fixation of the anterior pelvic ring with bone grafting.

PMID- 29198717
TI  - Seatbelt paths of the pregnant women sitting in the rear seat of a motor vehicle.
AB  - PURPOSE: Seatbelt use during pregnancy is important to improve maternal and fetal
      survival after motor vehicle collisions. However, because the rear seatbelt of a
      motor vehicle tends to make contact with the neck, even if it is adequately used,
      some pregnant women sitting in the rear seat opt not to fasten the belt. The
      purpose of this study is to explore seatbelt-neck contact for pregnant women
      sitting in the rear seat of a motor vehicle. METHODS: We carried out an
      anthropometric study. Japanese women who were >=30 weeks pregnant (n = 12) sat in
      the left side of the rear seat of a typical mid-size passenger sedan and fastened
      the seatbelt. Seating posture was investigated by measuring the coordinates of
      the anthropometric data points of the pregnant women (head, shoulder, hip joint,
      and knee joint). The belt path was analyzed by measuring the clearance between
      the belt and the sternum or navel. RESULTS: Among the 12 pregnant women at 33.9
      week +/- 3.3 week gestation, the shoulder belt deviated to the right side and
      subsequently contacted to the neck in four pregnant women (Contact group). The
      height of the Contact group was significantly shorter than that of Non-contact
      group (152.3 cm +/- 3.0 cm vs. 159.0 cm +/- 3.3 cm, p = 0.008). Regarding the
      relative position of the seatbelt to the subject's body, the distances from the
      top of the sternum to the center of the shoulder belt were significantly shorter
      in Contact group (3.9 cm +/- 3.5 cm) than that in the Non-contact group (8.0 cm
      +/- 1.6 cm, p = 0.03). However, no significant difference was found for the
      distance from the umbilicus to the center of the lap belt. CONCLUSION: Our
      findings show that because of short height and late term of pregnancy with
      protrusion of the abdomen, the shoulder belt deviates to the right or left,
      avoiding the protruded uterus, and subsequently makes contact with the neck.
      Seatbelt systems for rear seats need to be developed to improve passenger safety,
      especially for pregnant women.

PMID- 29198718
TI  - Quadratus femoris muscle pedicle bone flap transplantation in the treatment of
      femoral neck fracture for Chinese young and middle-aged patients: A systematic
      review and meta-analysis.
AB  - PURPOSE: To compare the efficacy of quadratus femoris muscle pedicle bone flap
      transplantation combined with hollow compression screw fixation versus AO hollow
      compression screw fixation in the treatment of femoral neck fracture for Chinese
      young and middle-aged patients. METHODS: Case-controlled studies (CCTs) were used
      to compare the two operative methods in the treatment of femoral neck fractures.
      Data were retrieved from the Cochrane Library, Pubmed Database, CNKI, Chinese
      Biomedical Database. Wanfang Data published during the period of January 2005 to
      December 2014. Methodological quality of the trials was critically assessed, and
      relevant data were extracted. Statistical Software Revman 5.0 was used for data
      analysis. RESULTS: Eight articles were included in the meta-analysis. The results
      showed that there was statistical significance in the rate of fracture healing
      [OR = 5.43, 95% CI (2.89, 10.20), p < 0.05], the rate of good function of hip
      joint [OR = 5.12, 95% CI (3.21, 8.17), p < 0.05], the rate of femoral head
      necrosis [OR = 4.21, 95% CI (2.02, 8.76), p < 0.05], the time of fracture healing
      [WMD = -46.85, 95% CI (-65.13, -28.56), p < 0.05] between the two groups.
      CONCLUSIONS: For the treatment of femoral neck fractures, the transplantation of
      quadratus femoris muscle pedicle bone flap combined with hollow compression
      screw; fixation is superior to the AO hollow compression screw fixation in terms
      of the rate; of fracture healing, the rate of good function of hip joint, the
      rate of femoral head; necrosis and the time of fracture healing.

PMID- 29198720
TI  - Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.
AB  - Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor
      cells that causes blindness within the first year of life. It occasionally occurs
      in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome
      sequencing in a multiplex family and three simplex case subjects with an atypical
      association of LCA with early-onset hearing loss, we identified two heterozygous
      mutations affecting Arg391 in beta-tubulin 4B isotype-encoding (TUBB4B).
      Inspection of the atomic structure of the microtubule (MT) protofilament reveals
      that the beta-tubulin Arg391 residue contributes to a binding pocket that
      interacts with alpha-tubulin contained in the longitudinally adjacent alphabeta
      heterodimer, consistent with a role in maintaining MT stability. Functional
      analysis in cultured cells overexpressing FLAG-tagged wild-type or mutant TUBB4B
      as well as in primary skin-derived fibroblasts showed that the mutant TUBB4B is
      able to fold, form alphabeta-heterodimers, and co-assemble into the endogenous MT
      lattice. However, the dynamics of growing MTs were consistently altered, showing
      that the mutations have a significant dampening impact on normal MT growth. Our
      findings provide a link between sensorineural disease and anomalies in MT
      behavior and describe a syndromic LCA unrelated to ciliary dysfunction.

PMID- 29198721
TI  - A Selection Operator for Summary Association Statistics Reveals Allelic
      Heterogeneity of Complex Traits.
AB  - In recent years, as a secondary analysis in genome-wide association studies
      (GWASs), conditional and joint multiple-SNP analysis (GCTA-COJO) has been
      successful in allowing the discovery of additional association signals within
      detected loci. This suggests that many loci mapped in GWASs harbor more than a
      single causal variant. In order to interpret the underlying mechanism regulating
      a complex trait of interest in each discovered locus, researchers must assess the
      magnitude of allelic heterogeneity within the locus. We developed a penalized
      selection operator for jointly analyzing multiple variants (SOJO) within each
      mapped locus on the basis of LASSO (least absolute shrinkage and selection
      operator) regression derived from summary association statistics. We found that,
      compared to stepwise conditional multiple-SNP analysis, SOJO provided better
      sensitivity and specificity in predicting the number of alleles associated with
      complex traits in each locus. SOJO suggested causal variants potentially missed
      by GCTA-COJO. Compared to using top variants from genome-wide significant loci in
      GWAS, using SOJO increased the proportion of variance prediction for height by
      65% without additional discovery samples or additional loci in the genome. Our
      empirical results indicate that human height is not only a highly polygenic
      trait, but also has high allelic heterogeneity within its established hundreds of
      loci.

PMID- 29198719
TI  - Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.
AB  - The genetic basis of earlobe attachment has been a matter of debate since the
      early 20th century, such that geneticists argue both for and against polygenic
      inheritance. Recent genetic studies have identified a few loci associated with
      the trait, but large-scale analyses are still lacking. Here, we performed a
      genome-wide association study of lobe attachment in a multiethnic sample of
      74,660 individuals from four cohorts (three with the trait scored by an expert
      rater and one with the trait self-reported). Meta-analysis of the three expert
      rater-scored cohorts revealed six associated loci harboring numerous candidate
      genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The
      large self-reported 23andMe cohort recapitulated each of these six loci.
      Moreover, meta-analysis across all four cohorts revealed a total of 49
      significant (p < 5 * 10-8) loci. Annotation and enrichment analyses of these 49
      loci showed strong evidence of genes involved in ear development and syndromes
      with auricular phenotypes. RNA sequencing data from both human fetal ear and
      mouse second branchial arch tissue confirmed that genes located among associated
      loci showed evidence of expression. These results provide strong evidence for the
      polygenic nature of earlobe attachment and offer insights into the biological
      basis of normal and abnormal ear development.

PMID- 29198722
TI  - A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual
      Disability without Frontonasal or Limb Malformations.
AB  - A recurrent de novo missense variant within the C-terminal Sin3-like domain of
      ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND),
      an autosomal-dominant severe frontonasal and limb malformation syndrome,
      associated with neurocognitive and motor delay, via a proposed gain-of-function
      effect. We present detailed phenotypic information on seven unrelated individuals
      with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the
      penultimate exon of ZSWIM6 who have severe-profound intellectual disability and
      additional central and peripheral nervous system symptoms but an absence of
      frontonasal or limb malformations. We show that the c.2737C>T variant does not
      trigger nonsense-mediated decay of the ZSWIM6 mRNA in affected individual-derived
      cells. This finding supports the existence of a truncated ZSWIM6 protein lacking
      the Sin3-like domain, which could have a dominant-negative effect. This study
      builds support for a key role for ZSWIM6 in neuronal development and function, in
      addition to its putative roles in limb and craniofacial development, and provides
      a striking example of different variants in the same gene leading to distinct
      phenotypes.

PMID- 29198724
TI  - Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause
      Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12
      Deletions.
AB  - Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene
      superfamily encoding TGF-beta-signaling proteins involved in bone and cartilage
      biology. Monoallelic deletions of 20p12 are variably associated with cleft
      palate, short stature, and developmental delay. Here, we report a cranioskeletal
      phenotype due to monoallelic truncating and frameshift BMP2 variants and
      deletions in 12 individuals from eight unrelated families that share features of
      short stature, a recognizable craniofacial gestalt, skeletal anomalies, and
      congenital heart disease. De novo occurrence and autosomal-dominant inheritance
      of variants, including paternal mosaicism in two affected sisters who inherited a
      BMP2 splice-altering variant, were observed across all reported families.
      Additionally, we observed similarity to the human phenotype of short stature and
      skeletal anomalies in a heterozygous Bmp2-knockout mouse model, suggesting that
      haploinsufficiency of BMP2 could be the primary phenotypic determinant in
      individuals with predicted truncating variants and deletions encompassing BMP2.
      These findings demonstrate the important role of BMP2 in human craniofacial,
      skeletal, and cardiac development and confirm that individuals heterozygous for
      BMP2 truncating sequence variants or deletions display a consistent distinct
      phenotype characterized by short stature and skeletal and cardiac anomalies
      without neurological deficits.

PMID- 29198726
TI  - Neopterin preconditioning prevents inflammasome activation in mammalian
      astrocytes.
AB  - Neopterin, a well-established biomarker for immune system activation, is found at
      increased levels in the cerebrospinal fluid of individuals affected by
      neurological/neurodegenerative diseases. Here, neopterin synthesis was
      investigated in different nerve cells (rodent and human) and in the mouse
      hippocampus under inflammatory stimuli. We also aimed to investigate whether
      neopterin preconditioning could modulate the inflammasome activation, a component
      of the innate immune system. Increased neopterin was detected in human nerve
      cells supernatants (highest secretion in astrocytes) exposed to
      lipopolysaccharide (LPS) and interferon-gamma (INF-gamma) and in the hippocampus
      of mice receiving LPS (0.33mg/kg; intraperitoneal). In parallel to the
      hippocampal-increased neopterin, it was observed a significant increase in the
      expression of the rate-limiting enzyme of its biosynthetic pathway, and both
      phenomena occurred before the inflammasome activation. Moreover, a significant
      inhibition of the inflammasome activation was observed in neopterin pre
      conditioned human astrocytes, when challenged with LPS, by reducing IL-1beta,
      caspase-1 and ASC expression or content, components of the NLRP3 inflammasome.
      Mechanistically, neopterin might induce eletrophilic stress and consequently the
      nuclear translocation of the transcription factor Nrf-2, and the anti
      inflammatory cytokines IL-10 and IL-1ra release, which would induce the
      inhibition of the inflammasome activation. Altogether, this strongly suggests an
      essential role of neopterin during inflammatory processes.

PMID- 29198723
TI  - DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation.
AB  - Genome-wide association studies have identified hundreds of genetic variants
      associated with blood pressure (BP), but sequence variation accounts for a small
      fraction of the phenotypic variance. Epigenetic changes may alter the expression
      of genes involved in BP regulation and explain part of the missing heritability.
      We therefore conducted a two-stage meta-analysis of the cross-sectional
      associations of systolic and diastolic BP with blood-derived genome-wide DNA
      methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010
      individuals of European, African American, and Hispanic ancestry. Of 31 discovery
      stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after
      Bonferroni correction (discovery: N = 9,828, p < 1.0 * 10-7; replication: N =
      7,182, p < 1.6 * 10-3). The replicated methylation sites are heritable (h2 > 30%)
      and independent of known BP genetic variants, explaining an additional 1.4% and
      2.0% of the interindividual variation in systolic and diastolic BP, respectively.
      Bidirectional Mendelian randomization among up to 4,513 individuals of European
      ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ)
      influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958
      (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six
      genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of
      triangular associations between methylation, gene expression, and BP. Additional
      integrative Mendelian randomization analyses of gene expression and DNA
      methylation suggested that the expression of TSPAN2 is a putative mediator of
      association between DNA methylation at cg23999170 and BP. These findings suggest
      that heritable DNA methylation plays a role in regulating BP independently of
      previously known genetic variants.

PMID- 29198725
TI  - Circadian clock-mediated regulation of blood pressure.
AB  - Most bodily functions vary over the course of a 24h day. Circadian rhythms in
      body temperature, sleep-wake cycles, metabolism, and blood pressure (BP) are just
      a few examples. These circadian rhythms are controlled by the central clock in
      the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks
      located throughout the body. Light and food cues entrain these clocks to the time
      of day and this synchronicity contributes to the regulation of a variety of
      physiological processes with effects on overall health. The kidney, brain,
      nervous system, vasculature, and heart have been identified through the use of
      mouse models and clinical trials as peripheral clock regulators of BP. The
      dysregulation of this circadian pattern of BP, with or without hypertension, is
      associated with increased risk for cardiovascular disease. The mechanism of this
      dysregulation is unknown and is a growing area of research. In this review, we
      highlight research of human and mouse circadian models that has provided insight
      into the roles of these molecular clocks and their effects on physiological
      functions. Additional tissue-specific studies of the molecular clock mechanism
      are needed, as well as clinical studies including more diverse populations
      (different races, female patients, etc.), which will be critical to fully
      understand the mechanism of circadian regulation of BP. Understanding how these
      molecular clocks regulate the circadian rhythm of BP is critical in the treatment
      of circadian BP dysregulation and hypertension.

PMID- 29198727
TI  - Neuroprotection afforded by circadian regulation of intracellular glutathione
      levels: A key role for miRNAs.
AB  - Circadian rhythms are approximately 24-h oscillations of physiological and
      behavioral processes that allow us to adapt to daily environmental cycles. Like
      many other biological functions, cellular redox status and antioxidative defense
      systems display circadian rhythmicity. In the central nervous system (CNS),
      glutathione (GSH) is a critical antioxidant because the CNS is extremely
      vulnerable to oxidative stress; oxidative stress, in turn, causes several fatal
      diseases, including neurodegenerative diseases. It has long been known that GSH
      level shows circadian rhythm, although the mechanism underlying GSH rhythm
      production has not been well-studied. Several lines of recent evidence indicate
      that the expression of antioxidant genes involved in GSH homeostasis as well as
      circadian clock genes are regulated by post-transcriptional regulator microRNA
      (miRNA), indicating that miRNA plays a key role in generating GSH rhythm.
      Interestingly, several reports have shown that alterations of miRNA expression as
      well as circadian rhythm have been known to link with various diseases related to
      oxidative stress. A growing body of evidence implicates a strong correlation
      between antioxidative defense, circadian rhythm and miRNA function, therefore,
      their dysfunctions could cause numerous diseases. It is hoped that continued
      elucidation of the antioxidative defense systems controlled by novel miRNA
      regulation under circadian control will advance the development of therapeutics
      for the diseases caused by oxidative stress.

PMID- 29198728
TI  - Flumioxazin metabolism in pregnant animals and cell-based protoporphyrinogen IX
      oxidase (PPO) inhibition assay of fetal metabolites in various animal species to
      elucidate the mechanism of the rat-specific developmental toxicity.
AB  - Flumioxazin, an N-phenylimide herbicide, inhibits protoporphyrinogen oxidase
      (PPO), a key enzyme in heme biosynthesis in mammals, and causes rat-specific
      developmental toxicity. The mechanism has mainly been clarified, but no research
      has yet focused on the contribution of its metabolites. We therefore conducted in
      vivo metabolism studies in pregnant rats and rabbits, and found 6 major known
      metabolites in excreta. There was no major rat-specific metabolite. The most
      abundant component in rat fetuses was APF, followed by flumioxazin and 5
      identified metabolites. The concentrations of flumioxazin and these metabolites
      in fetuses were lower in rabbits than in rats. In vitro PPO inhibition assays
      with rat and human liver mitochondria showed that flumioxazin is a more potent
      PPO inhibitor than the metabolites. There were no species differences in relative
      intensity of PPO inhibition among flumioxazin and these metabolites. Based on the
      results of these in vivo and in vitro experiments, we concluded that flumioxazin
      is the causal substance of the rat-specific developmental toxicity. As a more
      reliable test system for research on in vitro PPO inhibition, cell-based assays
      with rat, rabbit, monkey, and human hepatocytes were performed. The results were
      consistent with those of the mitochondrial assays, and rats were more sensitive
      to PPO inhibition by flumioxazin than humans, while rabbits and monkeys were
      almost insensitive. From these results, the species difference in the
      developmental toxicity was concluded to be due to the difference in sensitivity
      of PPO to flumioxazin, and rats were confirmed to be the most sensitive of these
      species.

PMID- 29198729
TI  - Study design and protocol for My Guide: An e-health intervention to improve
      patient-centered outcomes among Hispanic breast cancer survivors.
AB  - Breast cancer is the most commonly diagnosed non-skin cancer in women and the
      leading cause of death among Hispanic women living in the United States. Relative
      to non-Hispanic white women, Hispanic women report poorer health related quality
      of life (HRQoL) after treatment. Although eHealth interventions delivered via
      Smartphones are a viable approach to addressing supportive care accessibility
      issues while also integrating multidisciplinary approaches for improving HRQoL,
      few eHealth interventions have been developed that specifically target Hispanic
      breast cancer survivors (BCS). This manuscript describes the methodology of a
      multi-site, randomized controlled behavioral trial investigating the feasibility
      and preliminary efficacy of a Smartphone application aimed at improving HRQoL and
      cancer-specific distress among Hispanic BCS. Participants will be randomized to
      receive the intervention application, My Guide (psychoeducation & self-management
      program), or the health education control condition application, My Health
      (health education), for six weeks. All participants will also receive weekly
      telecoaching to enhance adherence to both control and intervention conditions. We
      will measure the study's primary outcomes, general and disease-specific HRQoL and
      cancer-specific distress, at three time points: prior to, immediately after the
      intervention, and eight weeks after initial application use. My Guide may have
      the potential to improve HRQoL, and to address issues of limited access to
      supportive care among Hispanic women recovering from breast cancer treatment.

PMID- 29198731
TI  - Discontinuing a non-steroidal anti-inflammatory drug (NSAID) in patients with
      knee osteoarthritis: Design and protocol of a placebo-controlled, noninferiority,
      randomized withdrawal trial.
AB  - BACKGROUND: Knee osteoarthritis (OA) is the most common cause of knee pain in
      older adults. Despite the limited data supporting their use, non-steroidal anti
      inflammatory drugs (NSAID) are among the most commonly prescribed medications for
      knee OA. The use of NSAIDs for knee pain warrants careful examination because of
      toxicity associated with this class of medications. METHODS: We describe the
      design of a placebo-controlled, noninferiority, randomized withdrawal trial to
      examine discontinuation of an NSAID in patients with painful knee OA.
      Participants will be veterans enrolled in the VA Healthcare System with knee OA
      pain despite NSAID use and/or relatively higher risk of NSAID toxicity. After a
      two-week run-in period where eligible subjects will replace their current NSAID
      with the study NSAID (meloxicam), those remaining eligible (target N=544) will be
      randomized to receive four weeks of either placebo or continued meloxicam. The
      primary outcome is knee pain (Western Ontario and McMaster Universities
      Osteoarthritis Index pain subscale, range 0-20) at four weeks post-randomization.
      The primary hypothesis is that placebo will be noninferior to (that is, not much
      worse than) meloxicam within a noninferiority margin of 1. Secondary outcomes
      include lower extremity disability, global impression of change, adherence to
      study medication and use of co-therapies. DISCUSSION: This study is the first
      clinical trial to date examining the effects of withdrawing an NSAID for OA knee
      pain. If successful, this trial will provide evidence against the continued use
      of NSAIDs in patients with OA knee pain. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01799213. Registered February 22, 2013.

PMID- 29198730
TI  - Designing a randomized controlled trial to evaluate a community-based narrative
      intervention for improving colorectal cancer screening for African Americans.
AB  - OBJECTIVE: To describe the methodology of a 2-arm randomized controlled trial
      that compared the effects of a narrative and didactic version of the Witness
      CARES (Community Awareness, Reach, & Empowerment for Screening) intervention on
      colorectal cancer screening behavior among African Americans, as well as the
      cognitive and affective determinants of screening. METHODS: Witness CARES
      targeted cognitive and affective predictors of screening using a culturally
      competent, community-based, narrative or didactic communication approach. New and
      existing community partners were recruited in two New York sites. Group
      randomization allocated programs to the narrative or didactic arm. Five phases of
      data collection were conducted: baseline, post-intervention, three-month, six
      month, and qualitative interviews. The primary outcome was screening behavior;
      secondary outcomes included cognitive and affective determinants of screening.
      RESULTS: A total of 183 programs were conducted for 2655 attendees. Of these
      attendees, 19.4% (N=516) across 158 programs (50% narrative; 50% didactic) were
      study-eligible and consented to participate. Half (45.6%) of the programs were
      delivered to new community partners and 34.8% were delivered at faith-based
      organizations. Mean age of the total sample was 64.7years and 75.4% were female.
      CONCLUSION: The planned number of programs was delivered, but the proportion of
      study-eligible attendees was lower than predicted. This community-based
      participatory research approach was largely successful in involving the community
      served in the development and implementation of the intervention and study.

PMID- 29198732
TI  - Application of process mapping to understand integration of high risk medicine
      care bundles within community pharmacy practice.
AB  - OBJECTIVE: The Scottish Patient Safety Programme - Pharmacy in Primary Care
      collaborative is a quality improvement initiative adopting the Institute of
      Healthcare Improvement Breakthrough Series collaborative approach. The programme
      developed and piloted High Risk Medicine (HRM) Care Bundles (CB), focused on
      warfarin and non-steroidal anti-inflammatories (NSAIDs), within 27 community
      pharmacies over 4 NHS Regions. Each CB involves clinical assessment and patient
      education, although the CB content varies between regions. To support national
      implementation, this study aims to understand how the pilot pharmacies integrated
      the HRM CBs into routine practice to inform the development of a generic HRM CB
      process map. METHODS: Regional process maps were developed in 4 pharmacies
      through simulation of the CB process, staff interviews and documentation of
      resources. Commonalities were collated to develop a process map for each HRM,
      which were used to explore variation at a national event. A single, generic
      process map was developed which underwent validation by case study testing.
      RESULTS: The findings allowed development of a generic process map applicable to
      warfarin and NSAID CB implementation. Five steps were identified as required for
      successful CB delivery: patient identification; clinical assessment; pharmacy CB
      prompt; CB delivery; and documentation. The generic HRM CB process map
      encompasses the staff and patients' journey and the CB's integration into routine
      community pharmacy practice. Pharmacist involvement was required only for
      clinical assessment, indicating suitability for whole-team involvement.
      CONCLUSIONS: Understanding CB integration into routine practice has positive
      implications for successful implementation. The generic process map can be used
      to develop targeted resources, and/or be disseminated to facilitate CB delivery
      and foster whole team involvement. Similar methods could be utilised within other
      settings, to allow those developing novel services to distil the key processes
      and consider their integration within routine workflows to effect maximal,
      efficient implementation and benefit to patient care.

PMID- 29198733
TI  - Virtual medicine: Utilization of the advanced cardiac imaging patient avatar for
      procedural planning and facilitation.
AB  - Advances in imaging technology have led to a paradigm shift from planning of
      cardiovascular procedures and surgeries requiring the actual patient in a "brick
      and mortar" hospital to utilization of the digitalized patient in the virtual
      hospital. Cardiovascular computed tomographic angiography (CCTA) and
      cardiovascular magnetic resonance (CMR) digitalized 3-D patient representation of
      individual patient anatomy and physiology serves as an avatar allowing for
      virtual delineation of the most optimal approaches to cardiovascular procedures
      and surgeries prior to actual hospitalization. Pre-hospitalization reconstruction
      and analysis of anatomy and pathophysiology previously only accessible during the
      actual procedure could potentially limit the intrinsic risks related to time in
      the operating room, cardiac procedural laboratory and overall hospital
      environment. Although applications are specific to areas of cardiovascular
      specialty focus, there are unifying themes related to the utilization of
      technologies. The virtual patient avatar computer can also be used for procedural
      planning, computational modeling of anatomy, simulation of predicted therapeutic
      result, printing of 3-D models, and augmentation of real time procedural
      performance. Examples of the above techniques are at various stages of
      development for application to the spectrum of cardiovascular disease processes,
      including percutaneous, surgical and hybrid minimally invasive interventions. A
      multidisciplinary approach within medicine and engineering is necessary for
      creation of robust algorithms for maximal utilization of the virtual patient
      avatar in the digital medical center. Utilization of the virtual advanced cardiac
      imaging patient avatar will play an important role in the virtual health care
      system. Although there has been a rapid proliferation of early data, advanced
      imaging applications require further assessment and validation of accuracy,
      reproducibility, standardization, safety, efficacy, quality, cost effectiveness,
      and overall value to medical care.

PMID- 29198734
TI  - [Clinical research and data collection during the investigation: Influence of a
      dedicated staff].
AB  - OBJECTIVE: In clinical research, the recourse to a staff dedicated as CRA with
      the investigator is common practice to facilitate the work of collection and
      limiting the missing data (MD). We, therefore, looked for the interest of the
      recourse of such personnel to data collection. METHODS: MD were classified
      according to five categories: clinical, para-clinical, treatment, adverse events
      (serious) and others. Studies were separated in two designs, one-off studies
      during a single visit (so-called "no follow") and studies on the duration and
      including several visits (say "with follow"). Similarly, studies were
      differentiated according to their type of collection "Without ARC" if the data
      were collected by an investigator, and studies "With ARC". RESULTS: The presence
      of a CRA can reduce the number of MD whatever their type (Student test:
      P<0.0001): With CRA mean of MD is 4.8%+/-8.4% and Without CRA mean of MD is
      22.1%+/-17.0%. CONCLUSION: The delegation of data collection to a staff dedicated
      reduces significantly the percentage of missing data.

PMID- 29198735
TI  - Outpatient therapy for acute symptomatic pulmonary embolism diagnosed in the
      emergency department: Time to improve the evidence base.

PMID- 29198736
TI  - Venous Thromboembolic Complications to Hysterectomy for Benign Disease: A
      Nationwide Cohort Study.
AB  - STUDY OBJECTIVE: To estimate the risk of venous thromboembolic complications
      after abdominal, laparoscopic, and vaginal hysterectomy when performed for benign
      disorders. DESIGN: A nationwide cohort study (Canadian Task Force classification
      II-2). SETTING: Data from Danish national registers on all women undergoing
      hysterectomy for benign conditions from 1996 to 2015. PATIENTS: Women aged 18
      years and older who underwent hysterectomy for benign disease were stratified
      into 3 groups according to the hysterectomy approach: abdominal, laparoscopic, or
      vaginal. INTERVENTIONS: Hysterectomy. MEASUREMENTS AND MAIN RESULTS: Eighty-nine
      thousand nine hundred thirty-one women met the inclusion criteria. Venous
      thromboembolism (VTE) as a diagnosis or cause of death was identified. The risk
      of postoperative VTE was examined with Cox proportional hazard models adjusting
      for age, surgical approach, and relevant comorbidities. The mean age was 49.9,
      47.9, and 54.3 years for women with abdominal, laparoscopic, and vaginal
      hysterectomy, respectively. The crude incidences of VTE within 30 days after
      hysterectomy were 0.24% (n = 142), 0.13% (n = 12), and 0.10% (n = 21). The most
      important predictors of VTE were the approach to hysterectomy and a history of
      thromboembolic disease. In the multivariable analysis, the risk of VTE was
      significantly reduced with laparoscopic hysterectomy (hazard ratio [HR] = 0.51;
      95% confidence interval [CI], 0.28-0.92; p = .03) and vaginal hysterectomy (HR =
      0.39; 95% CI, 0.24-0.63; p < .001) when compared with the abdominal procedure.
      Data on postoperative heparin thromboprophylaxis were available in 53 566
      patients, and the adjusted HR was 0.63 (95% CI, 0.42-0.96; p = .03) in patients
      receiving heparin thromboprophylaxis. CONCLUSION: The 30-day cumulative incidence
      of VTE after hysterectomy for benign conditions was low overall (0.19%).
      Laparoscopic hysterectomy and vaginal hysterectomy carry a lower risk than the
      abdominal procedure. Postoperative heparin thromboprophylaxis significantly
      reduces the risk of VTE and should be considered, especially if risk factors are
      present.

PMID- 29198737
TI  - Stabilization of the Fourth Metatarsal-Cuboid Lateral Lisfranc Injury: Early
      Results of an Innovative Technique Using Suture Anchors.
AB  - This report presents an innovative surgical technique for the correction of
      cuboid-metatarsal subluxation at the level of the lateral Lisfranc joint. This
      stabilization technique reinforces the dorsal fourth tarsometatarsal ligament by
      incorporating sutures and anchors, establishing a more stable joint. The data
      from 5 female patients undergoing stabilization using a suture anchor construct
      were reviewed. All 5 patients were able to resume their activities, including the
      adolescent athletes. Anatomic reconstruction of the dorsal fourth tarsometatarsal
      ligament complex can lead to full mechanical and functional stability, which
      ultimately allows for a return to activity, even in highly demanding sports and
      athletes.

PMID- 29198738
TI  - Corrections.

PMID- 29198739
TI  - Why the antibiotic resistance crisis requires a One Health approach.

PMID- 29198740
TI  - Early transmissible ampicillin resistance in zoonotic Salmonella enterica
      serotype Typhimurium in the late 1950s: a retrospective, whole-genome sequencing
      study.
AB  - BACKGROUND: Ampicillin, the first semi-synthetic penicillin active against
      Enterobacteriaceae, was released onto the market in 1961. The first outbreaks of
      disease caused by ampicillin-resistant strains of Salmonella enterica serotype
      Typhimurium were identified in the UK in 1962 and 1964. We aimed to date the
      emergence of this resistance in historical isolates of S enterica serotype
      Typhimurium. METHODS: In this retrospective, whole-genome sequencing study, we
      analysed 288 S enterica serotype Typhimurium isolates collected between 1911 and
      1969 from 31 countries on four continents and from various sources including
      human beings, animals, feed, and food. All isolates were tested for antimicrobial
      drug susceptibility with the disc diffusion method, and isolates shown to be
      resistant to ampicillin underwent resistance-transfer experiments. To provide
      insights into population structure and mechanisms of ampicillin resistance, we
      did whole-genome sequencing on a subset of 225 isolates, selected to maximise
      source, spatiotemporal, and genetic diversity. FINDINGS: 11 (4%) of 288 isolates
      were resistant to ampicillin because of acquisition of various beta lactamase
      genes, including blaTEM-1, carried by various plasmids, including the virulence
      plasmid of S enterica serotype Typhimurium. These 11 isolates were from three
      phylogenomic groups. One isolate producing TEM-1 beta lactamase was isolated in
      France in 1959 and two isolates producing TEM-1 beta lactamase were isolated in
      Tunisia in 1960, before ampicillin went on sale. The vectors for ampicillin
      resistance were different from those reported in the strains responsible for the
      outbreaks in the UK in the 1960s. INTERPRETATION: The association between
      antibiotic use and selection of resistance determinants is not as direct as often
      presumed. Our results suggest that the non-clinical use of narrow-spectrum
      penicillins (eg, benzylpenicillin) might have favoured the diffusion of plasmids
      carrying the blaTEM-1 gene in S enterica serotype Typhimurium in the late 1950s.
      FUNDING: Institut Pasteur, Sante publique France, the French Government's
      Investissement d'Avenir programme, the Fondation Le Roch-Les Mousquetaires.

PMID- 29198741
TI  - Pregnancy as an early stress test for cardiovascular and kidney disease
      diagnosis.
AB  - OBJECTIVES: Pregnancy is a cardiometabolic and renal stress test for women,
      primarily when associated with hypertension syndrome, which can have deleterious
      effects in the long term. We undertook this study to make a long-term evaluation
      on these women. STUDY DESIGN: A retrospective cohort study was conducted to
      investigate voluntary women who had pregnancy-induced hypertension syndrome
      versus normal pregnancy. MAIN OUTCOME MEASURES: We evaluated a total of 85 women,
      divided in case (n = 25) and control (n = 60) groups, by clinical, anthropometric
      and epidemiological profiles, general, metabolic and renal tests, and risk
      stratification for cardiovascular disease (CVD) and chronic kidney disease (CKD).
      RESULTS: The case group showed a higher incidence of hypertension (P = .003),
      shorter period between its diagnosis and end of pregnancy (P < .001) and lower
      age at diagnosis (P = .033); higher weight (P < .001), body mass index (BMI) (P <
      .001), waist-to-height ratio (p = .001) and abdominal circumference (P < .001);
      higher fat percentage (P = .004) and weight to lose (P < .001) as measured by
      bioimpedance; lower estimate glomerular filtration rate (eGFR) by the Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (P = .021), greater
      difference between estimated vascular age and real age (P = .008) according to
      Framingham Risk Score (2008) and higher frequency of metabolic syndrome (P <
      .001). CONCLUSIONS: Women who had pregnancy-induced hypertension syndrome were
      found with a higher incidence of obesity, metabolic syndrome and hypertension,
      earlier onset of hypertension, higher estimated vascular age and lower eGFR.
      These findings reinforce the importance of investigating the history of
      hypertension syndrome in pregnancy, which should be considered an indicator to be
      followed long term after childbirth.

PMID- 29198742
TI  - Prediction of adverse maternal outcomes from pre-eclampsia and other hypertensive
      disorders of pregnancy: A systematic review.
AB  - BACKGROUND: The hypertensive disorders of pregnancy are a leading cause of
      maternal and perinatal mortality and morbidity. The ability to predict these
      complications using simple tests could aid in management and improve outcomes. We
      aimed to systematically review studies that reported on potential predictors of
      adverse maternal outcomes among women with a hypertensive disorder of pregnancy.
      METHODS: We searched MEDLINE, Embase and CINAHL (inception - December 2016) for
      studies of predictors of severe maternal complications among women with a
      hypertensive disorder of pregnancy. Studies were selected in a two-stage process
      by two independent reviewers, excluding those reporting only on adverse fetal
      outcomes. We extracted data on study and test(s) characteristics and outcomes.
      Accuracy of prediction was assessed using sensitivity, specificity, likelihood
      ratios and area under the receiver operating curve (AUROC). Strong evidence of
      prediction was taken to be a positive likelihood ratio >10 or a negative
      likelihood ratio <0.1, and for multivariable models, an AUROC >=0.70. Bivariate
      random effects models were used to summarise performance when possible. RESULTS:
      Of 32 studies included, 28 presented only model development and four examined
      external validation. Tests included symptoms and signs, laboratory tests and
      biomarkers. No single test was a strong independent predictor of outcome. The
      most promising prediction was with multivariable models, especially when oxygen
      saturation, or chest pain/dyspnea were included. CONCLUSION: Future studies
      should investigate combinations of tests in multivariable models (rather than
      single predictors) to improve identification of women at high risk of adverse
      outcomes in the setting of the hypertensive disorders of pregnancy.

PMID- 29198743
TI  - Apigenin and luteolin display differential hypocholesterolemic mechanisms in mice
      fed a high-fat diet.
AB  - Hypercholesterolemia is a major risk factor in the development of
      atherosclerosis. High blood cholesterol can be the result of increased
      biosynthesis or reduced elimination of cholesterol in the system. Increased
      consumption of fruits and vegetables is recommended for patients suffering from
      hypercholesterolemia. The plant food flavones apigenin and luteolin have
      previously been shown to suppress the synthesis of cholesterol in human
      hepatocytes. The effectiveness of these two flavones in controlling blood
      cholesterol was examined in a mouse model in the present study. Mice were fed a
      high-fat diet and apigenin or luteolin at 50 and 250 ppm was mixed in the diet.
      After 8 weeks of treatment, the administration of 250 ppm apigenin or 250 ppm
      luteolin could modulate the total and serum non-HDL cholesterol. The expressions
      of srebf-2 mRNA, Srebp-2 protein and Hmgcr protein were decreased in the livers
      of apigenin-treated mice; meanwhile, AMPK was activated in this group of mice. In
      contrast, suppressed ncp1l1 and induced abcg-5/8 mRNA expressions were seen in
      the intestinal mucosa of luteolin-fed animals. Increased fecal cholesterol
      content was also observed in the luteolin-treated mice. These results revealed
      that apigenin suppressed the biosynthesis of cholesterol, whereas luteolin
      promoted the elimination of cholesterol. In summary, this study illustrated that
      the two flavones could attenuate high-fat feeding-induced hypercholesterolemia in
      two different mechanisms.

PMID- 29198744
TI  - Are plant-based functional foods better choice against cancer than single
      phytochemicals? A critical review of current breast cancer research.
AB  - Breast cancer is the most common malignancy in women worldwide. Over 90% of all
      breast cancer cases are of different 'sporadic' cell types, thus placing emphasis
      on the need for breast cancer prevention and new effective treatment strategies.
      In recent years, pre-clinical research provides growing evidence regarding the
      beneficial action of bioactive plant-derived substances - phytochemicals, on
      multiple cancer-related biological pathways. The important natural source of
      various phytochemicals with anti-oncogenic properties are plant-based functional
      foods. It is hypothesized that a significant anti-tumour activity of plant-based
      functional foods are the result of a combination of various phytochemicals rather
      than an isolated agent. The mixture of phytochemicals with various biological
      activities present in whole foods could have additive or synergistic effects
      against carcinogenesis. Clinically, it is very important to compare the effect of
      the isolated phytochemicals against the mixture of phytochemicals present in
      specific plant-based functional foods. Therefore, the purpose of this review
      article is to compare anticancer activities of isolated phytochemicals and plant
      based functional foods for the prevention and therapy of breast carcinoma. Our
      conclusion supports the hypothesis that a mixture of wide range of phytochemicals
      with a plethora of biological activities present in whole plant-derived foods
      could have additive or synergistic effects against breast cancer. Although, the
      lack of parallel comparative studies between whole natural foods versus isolated
      plant compounds limits our conclusion, future pre-clinical and clinical studies
      evaluating this issue is required.

PMID- 29198745
TI  - Orientin, a C-glycosyl dietary flavone, suppresses colonic cell proliferation and
      mitigates NF-kappaB mediated inflammatory response in 1,2-dimethylhydrazine
      induced colorectal carcinogenesis.
AB  - Orientin, a C-glycosyl dietary flavone profusely found in rooibos tea and passion
      fruit have gained much attention owing to their multiple pharmacological
      potentials. The present study intends to investigate the anti-proliferative and
      anti-inflammatory efficacy of Orientin in 1,2-dimethyl hydrazine (DMH) induced
      colorectal cancer (CRC) in rats. Animals were arbitrarily segmented into six
      groups and fed with high-fat diet. Group 1 served as control. Group 2 received
      weekly subcutaneous injections of DMH (20 mg/kg b.w.), for first 15 weeks. Group
      3 administered with Orientin (10 mg/kg b.w., i.p.) whereas Groups 4-6 treated
      with Orientin in three phases, namely initiation (along with DMH), post
      initiation (post-DMH injection) and entire period. Orientin ameliorates tumor
      marker levels significantly (p < 0.05) and reinstates the histological changes
      induced by DMH. The proliferative markers (PCNA and Ki67) were observed to be
      suppressed significantly (p < 0.05) in Orientin treated rats. Orientin abrogates
      (p < 0.05) the inflammatory mast cells and diminishes the expression of pro
      inflammatory NF-kappaB and cytokines (TNF-alpha and IL-6). It also down-regulates
      over expression of inflammatory inducible enzymes (iNOS and COX-2) significantly
      (p < 0.05) and further substantiated by GLIDE XP and QPLD studies. Overall
      results promptly elucidate the anti-proliferative and anti-inflammatory efficacy
      of Orientin against CRC. Orientin can be developed as a promising
      chemotherapeutic agent, on further validation of other molecular mechanisms.

PMID- 29198747
TI  - Recent advances in cancer immunology and immunology-based anticancer therapies.
AB  - Cancer immunotherapies offer promise for cure of cancer with specificity and
      minimal toxicity. Recent developments in cancer immunology have led to the better
      understanding of role of immune regulatory mechanisms in cancer. There is rapid
      progress in this field in the last few years. Several clinical studies report the
      efficacy of immunotherapies for treating cancer. The immunology-based anticancer
      therapies have shown better safety profiles in clinic as compared to other
      chemotherapeutic agents, thus increasing interest in this area. This review
      summarizes recent advances in cancer immunology and discusses tumor
      microenvironment and immunology-based anticancer therapies, including vaccines
      and therapies targeting immune checkpoints.

PMID- 29198746
TI  - Valproic acid attenuates inflammation of optic nerve and apoptosis of retinal
      ganglion cells in a rat model of optic neuritis.
AB  - AIMS: Optic neuritis (ON) is an inflammatory disease of the optic nerve, which
      often occurs in patients with multiple sclerosis (MS) and leads to retinal
      ganglion cell (RGC) death and even severe visual loss. Valproic acid (VPA) is a
      short-chain branched fatty acid with anti-epileptic, neuro-protective and anti
      inflammatory effects. Here, we examined the effects of VPA in experimental
      autoimmune encephalomyelitis (EAE) rats and explored the underlying mechanisms.
      MAIN METHODS: EAE was induced by subcutaneous injection with myelin basic
      protein, emulsified with complete Freund's adjuvant and Mycobacterium
      tuberculosis H37Ra into the Lewis rats. Subsequently, animals in the VPA groups
      were treated orally with VPA (250 or 500 mg/kg) once a day for 13 days. KEY
      FINDINGS: VPA treatment significantly attenuated inflammation and microgliosis in
      optic nerve in EAE-ON rats, as evidenced by the decrease in the mRNA levels of
      interferon (INF)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-17, and inducible nitric oxide synthase (iNOS), the suppression in
      nuclear factor (NF)-kappaB signal pathway as well as the down-regulation of CD11b
      expression in optic nerve. Additionally, the apoptotic RGCs were remarkably
      increased in the EAE retina, which was inhibited by VPA treatment. Consistent
      with the TUNEL staining, VPA administration also obviously suppressed the ratio
      of Bax: Bcl-2 and the expression of cleaved caspase-3 and PARP in optic nerve in
      EAE rats. SIGNIFICANCE: Our findings demonstrated that VPA treatment could
      prevent inflammation responses and RGC apoptosis in optic nerve in EAE-ON rats,
      suggesting that VPA may be available for optic nerve protection during ON.

PMID- 29198748
TI  - Microparticles from stored red blood cells promote a hypercoagulable state in a
      murine model of transfusion.
AB  - BACKGROUND: Red blood cell-derived microparticles are biologically active,
      submicron vesicles shed by erythrocytes during storage. Recent clinical studies
      have linked the duration of red blood cell storage with thromboembolic events in
      critically ill transfusion recipients. In the present study, we hypothesized that
      microparticles from aged packed red blood cell units promote a hypercoagulable
      state in a murine model of transfusion. METHODS: Microparticles were isolated
      from aged, murine packed red blood cell units via serial centrifugation. Healthy
      male C57BL/6 mice were transfused with microparticles or an equivalent volume of
      vehicle, and whole blood was harvested for analysis via rotational
      thromboelastometry. Serum was harvested from a separate set of mice after
      microparticles or saline injection, and analyzed for fibrinogen levels. Red blood
      cell-derived microparticles were analyzed for their ability to convert
      prothrombin to thrombin. Finally, mice were transfused with either red blood cell
      microparticles or saline vehicle, and a tail bleeding time assay was performed
      after an equilibration period of 2, 6, 12, or 24 hours. RESULTS: Mice injected
      with red blood cell-derived microparticles demonstrated an accelerated clot
      formation time (109.3 +/- 26.9 vs 141.6 +/- 28.2 sec) and increased alpha angle
      (68.8 +/- 5.0 degrees vs 62.8 +/- 4.7 degrees) compared with control (each P <
      .05). Clotting time and maximum clot firmness were not significantly different
      between the 2 groups. Red blood cell-derived microparticles exhibited a
      hundredfold greater conversion of prothrombin substrate to its active thrombin
      form (66.60 +/- 0.03 vs 0.70 +/- 0.01 peak OD; P<.0001). Additionally, serum
      fibrinogen levels were lower in microparticles-injected mice compared with saline
      vehicle, suggesting thrombin-mediated conversion to insoluble fibrin (14.0 vs
      16.5 ug/mL, P<.05). In the tail bleeding time model, there was a more rapid
      cessation of bleeding at 2 hours posttransfusion (90.6 vs 123.7 sec) and 6 hours
      posttransfusion (87.1 vs 141.4 sec) in microparticles-injected mice as compared
      with saline vehicle (each P<.05). There was no difference in tail bleeding time
      at 12 or 24 hours. CONCLUSION: Red blood cell-derived microparticles induce a
      transient hypercoagulable state through accelerated activation of clotting
      factors.

PMID- 29198750
TI  - Comment on: weight loss after bariatric surgery in obese adolescents: a
      systematic review and meta-analysis.

PMID- 29198749
TI  - Mitochondrial fission is associated with UCP1 activity in human brite/beige
      adipocytes.
AB  - OBJECTIVE: Thermogenic adipocytes (i.e. brown or brite/beige adipocytes) are able
      to burn large amounts of lipids and carbohydrates as a result of highly active
      mitochondria and enhanced uncoupled respiration, due to UCP1 activity. Although
      mitochondria are the key organelles for this thermogenic function, limited human
      data are available. METHODS/RESULTS: We characterized changes in the
      mitochondrial function of human brite adipocytes, using hMADS cells as a model of
      white- to brite-adipocyte conversion. We found that profound molecular
      modifications were associated with morphological changes in mitochondria. The
      fission process was partly driven by the DRP1 protein, which also promoted
      mitochondrial uncoupling. CONCLUSION: Our data demonstrate that white-to-brite
      conversion of human adipocytes relies on molecular, morphological and functional
      changes in mitochondria, which enable brite/beige cells to carry out
      thermogenesis.

PMID- 29198751
TI  - Diabetes resolution after one anastomosis gastric bypass.
AB  - BACKGROUND: Diabetes and other obesity-related diseases are a worldwide pandemic
      that transcends geographic borders as well as socioeconomic levels. Currently, it
      is well known that medical treatment alone is insufficient to ensure adequate and
      sustainable weight loss and co-morbidity resolution. It has been well proven that
      bariatric surgery can produce almost immediate resolution of diabetes and other
      co-morbidities as well as long-term weight loss. OBJECTIVES: Here, we present our
      experience with the one anastomosis gastric bypass (OAGB) in terms of weight loss
      and diabetes resolution with 1 year of follow-up. SETTING: Large, metropolitan,
      tertiary, university hospital. METHODS: A retrospective analysis of all patients
      who underwent OAGB between March 2015 and March 2016 was performed. Patient
      demographic characteristics, co-morbidities, operative and postoperative data, as
      well as first year outcomes were collected and analyzed. RESULTS: There were 407
      patients who underwent OAGB (254 females, average age 41.8 +/- 12.05 yr, body
      mass index = 41.7 +/- 5.77 kg/m2). Of patients, 102 (25.1%) had diabetes with
      average glycosylated hemoglobin of 8.64 +/- 1.94 g%, 93 (22.8%) had hypertension,
      123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) had obstructive sleep
      apnea. The average length of hospital stay was 2.2 +/- .84 days (range, 2-10 d).
      The average excess weight loss 1 year after surgery was 88.9 +/- 27.3. After 1
      year, follow-up data were available for more than 85% of the study's general
      population. Of 102 diabetic patients, only 8 (7.8%) were still considered
      diabetic and taking antidiabetic medication, with an average glycosylated
      hemoglobin of 5.4 +/- 0.6. CONCLUSIONS: OAGB may be performed safely and with
      promising efficacy as both a primary and a revisional bariatric surgery, and it
      offers excellent resolution of diabetes.

PMID- 29198752
TI  - Comment on: preoperative progressive pneumoperitoneum in obese patients with loss
      of domain hernias.

PMID- 29198754
TI  - Divergent Connectivity of Homologous Command-like Neurons Mediates Segment
      Specific Touch Responses in Drosophila.
AB  - Animals adaptively respond to a tactile stimulus by choosing an ethologically
      relevant behavior depending on the location of the stimuli. Here, we investigate
      how somatosensory inputs on different body segments are linked to distinct motor
      outputs in Drosophila larvae. Larvae escape by backward locomotion when touched
      on the head, while they crawl forward when touched on the tail. We identify a
      class of segmentally repeated second-order somatosensory interneurons, that we
      named Wave, whose activation in anterior and posterior segments elicit backward
      and forward locomotion, respectively. Anterior and posterior Wave neurons extend
      their dendrites in opposite directions to receive somatosensory inputs from the
      head and tail, respectively. Downstream of anterior Wave neurons, we identify
      premotor circuits including the neuron A03a5, which together with Wave, is
      necessary for the backward locomotion touch response. Thus, Wave neurons match
      their receptive field to appropriate motor programs by participating in different
      circuits in different segments.

PMID- 29198753
TI  - Cell therapies for hematological malignancies: don't forget non-gene-modified t
      cells!
AB  - Cell therapy currently performs an important role in the treatment of patients
      with various hematological malignancies. The response to the cell therapy is
      regulated by multiple factors including the patient's immune system status,
      genetic profile, stage at diagnosis, age, and underlying disease. Cell therapy
      that does not require genetic manipulation can be mediated by donor lymphocyte
      infusion strategies, selective depletion in the post-transplant setting and the
      ex vivo expansion of antigen-specific T cells. For hematologic malignancies, cell
      therapy is contributing to enhanced clinical responses and overall survival and
      the immune response to cell therapy is predictive of response in multiple cancer
      types. In this review we summarize the available T cell therapeutics that do not
      rely on gene engineering for the treatment of patients with blood cancers.

PMID- 29198755
TI  - Differentiation between Oppositely Oriented Microtubules Controls Polarized
      Neuronal Transport.
AB  - Microtubules are essential for polarized transport in neurons, but how their
      organization guides motor proteins to axons or dendrites is unclear. Because
      different motors recognize distinct microtubule properties, we used optical
      nanoscopy to examine the relationship between microtubule orientations,
      stability, and modifications. Nanometric tracking of motors to super-resolve
      microtubules and determine their polarity revealed that in dendrites, stable and
      acetylated microtubules are mostly oriented minus-end out, while dynamic and
      tyrosinated microtubules are oriented oppositely. In addition, microtubules with
      similar orientations and modifications form bundles that bias transport.
      Importantly, because the plus-end-directed Kinesin-1 selectively interacts with
      acetylated microtubules, this organization guides this motor out of dendrites and
      into axons. In contrast, Kinesin-3 prefers tyrosinated microtubules and can enter
      both axons and dendrites. This separation of distinct microtubule subsets into
      oppositely oriented bundles constitutes a key architectural principle of the
      neuronal microtubule cytoskeleton that enables polarized sorting by different
      motor proteins.

PMID- 29198756
TI  - CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian
      Sensory Neurons.
AB  - Action potential induces membrane depolarization and triggers intracellular free
      Ca2+ concentration (Ca2+)-dependent secretion (CDS) via Ca2+ influx through
      voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered
      by the action potential per se-Ca2+-independent but voltage-dependent secretion
      (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular
      mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their
      linker. Specifically, the voltage-gated N-type Ca2+ channel (CaV2.2) is the
      voltage sensor triggering CiVDS, the SNARE complex functions as the vesicle
      fusion machinery, the "synprint" of CaV2.2 serves as a linker between the voltage
      sensor and the fusion machinery, and ATP is a cargo of CiVDS vesicles. Thus,
      CiVDS releases ATP from the soma while CDS releases glutamate from presynaptic
      terminals, establishing the CaV2.2-SNARE "voltage-gating fusion pore" as a novel
      pathway co-existing with the canonical "Ca2+-gating fusion pore" pathway for
      neurotransmitter release following action potentials in primary sensory neurons.

PMID- 29198758
TI  - Kinetics of 3H, 90Sr and 137Cs content changes in hydrosphere in the Vltava River
      system (Czech Republic).
AB  - The paper presents results and interpretation of long-term monitoring of
      occurrence and behaviour of radioisotopes 3H, 90Sr, and 137Cs in the vicinity of
      the Temelin Nuclear Power Plant. 3H, 90Sr, and 137Cs originate predominantly from
      residual contamination due to atmospheric nuclear weapons tests and the Chernobyl
      disaster in the last century. Monitoring of radionuclides comprised surface
      waters, river sediments, aquatic plants, and fish. This enables an up-to-date
      appraisal of the Temelin Nuclear Power Plant impact on the hydrosphere in all
      indicators at standard power plant operation, as well as at critical situations.
      The time and spatial variability of these radionuclide concentrations were
      monitored in the hydrosphere at in- and out-flow of the Orlik Water Reservoir.
      The basic evaluated radioecological characteristics can be used in assessing the
      long-term kinetics of decline and behaviour of radionuclides and their potential
      release into the environment. A very slow decline in 3H concentration at
      unaffected sites was observed. At sites downstream from the power plant the 3H
      concentrations were significantly higher, an evident impact of the power plant
      operation. A decline in 90Sr and 137Cs concentrations was observed in all the
      monitored indicators. Also, the characteristic effective and ecological half
      lives were evaluated.

PMID- 29198757
TI  - Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal
      GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area.
AB  - Rhythmic medial septal (MS) GABAergic input coordinates cortical theta
      oscillations. However, the rules of innervation of cortical cells and regions by
      diverse septal neurons are unknown. We report a specialized population of septal
      GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3
      area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra
      cells show the highest rhythmicity among MS neurons and fire with short burst
      duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow
      irregular oscillations, coincident with highest hippocampal excitability. Teevra
      cells synaptically target GABAergic axo-axonic and some CCK interneurons in
      restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases
      from septal to temporal termination of individual axons. We hypothesize that
      Teevra neurons coordinate oscillatory activity across the septo-temporal axis,
      phasing the firing of specific CA3 interneurons, thereby contributing to the
      selection of pyramidal cell assemblies at the theta trough via disinhibition.
      VIDEO ABSTRACT.

PMID- 29198759
TI  - Lowered reference limits for hCG improve follow-up of patients with hCG-producing
      tumors.
AB  - BACKGROUND: Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors,
      but can also be elevated in benign conditions such as primary hypogonadism, where
      hCG is produced by the pituitary gland. In our experience, the reference limits
      for hCG (Elecsys hCG+beta-assay, Roche Diagnostics), were unnecessarily high and
      did not reflect levels encountered in clinical practice. We wanted to establish
      new reference limits to increase the clinical utility of the hCG-assay. METHODS:
      We analysed hCG in serum samples from a healthy adult population and in a cohort
      of testicular cancer survivors. The gonadotropins LH and FSH were measured in the
      cohort and in a selection of the reference population to assess gonadal function.
      RESULTS: We found low hCG levels for all men and women <45years (97.5 percentiles
      0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal
      FSH and LH. Due to assay limitations, we suggest a common reference limit of
      <0.3IU/L. For the age group >=45, the 97.5 percentiles in the healthy population
      were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the
      reference population and the cohort (n=732), hCG levels exceeding the reference
      limit could be fully explained by reduced gonadal function indicated by elevated
      LH and FSH levels. CONCLUSION: The Elecsys hCG+beta-assay should have lower
      reference limits than recommended by the manufacturer, with important
      implications for tumor follow-up. Elevated hCG is rare with intact gonadal
      function, both in a normal population and among survivors of testicular cancer,
      and should lead to further investigations when encountered in clinical practice.

PMID- 29198761
TI  - Diagnostics, treatment and secondary prevention of ischemic stroke in the
      Silesian Province, Poland between 2009 and 2015.
AB  - BACKGROUND: The available data on diagnostics and treatment of ischemic stroke
      (IS) in Poland come mainly from non-representative cohorts or are outdated.
      OBJECTIVE: Therefore, the current study was done to access the most recent data
      on IS in the industrial region that covers 12% of the country's population.
      MATERIALS & METHODS: Analysis of the data from stroke questionnaires, obligatory
      for all patients hospitalized due to acute stroke and administered by the
      National Health Fund (the only public health insurer in Poland) between 2009 and
      2015 (n=81,193). RESULTS: The number of hospitalizations due to IS in the
      Silesian Province was 69,403 and constituted 85.5% of all stroke cases reported
      to the NHF between 2009 and 2015. Neuroimaging of the brain (CT/MRI) was
      performed in 68,696 (99%) subjects, while ultrasonography of extra- and/or
      intracranial arteries in 57,886 (83.4%). The rtPA therapy was applied in 3282
      patients (4.7% of all IS subjects). The rate of patients treated with rtPA
      gradually increased (1.2% in 2009, 9.3% in 2015). Among all patients with IS,
      57,636 (83.1%) subjects were administered antiplatelet drugs, 16,199 (23.3%) -
      oral anticoagulants, and 55,971 (80.7%) - antihypertensive drugs. Also, 2260
      (3.3%) patients were referred for vascular intervention. In subjects with
      cardioembolic stroke etiology, 37.8% were treated with anticoagulants.
      CONCLUSIONS: There has been observed a significant improvement in the quality of
      diagnosis and treatment of acute ischemic stroke during recent years. However,
      further actions are required both in terms of reperfusion treatment (thrombolysis
      and/or thrombectomy) and secondary prevention of stroke.

PMID- 29198762
TI  - Synthesis of calcium phosphate nanostructures by combustion in solution as a
      potential encapsulant system of drugs with photodynamic properties for the
      treatment of cutaneous leishmaniasis.
AB  - The traditional drugs used in the treatment of cutaneous leishmanisis (CL) have
      multiple disadvantages, such as high toxicity, high costs, and more recently the
      appearance of parasites resistant to those drugs. For this reason, some research
      has focused on the development of new drugs or treatment therapies. Photodynamic
      therapy (PDT) that involves the use of a photosensitive or photosensitizing
      compound capable of producing reactive oxygen species to which Leishmania
      parasites are sensitive, has emerged as an alternative for the treatment of CL.
      However, some of these sensitizing compounds exhibit some toxicity (cytotoxicity,
      allergic reaction, etc), low selectivity, and some of them are insoluble in
      aqueous media limiting their use. Therefore, the PDT can be improved using
      encapsulation systems which protect drugs, prevent their degradation, help them
      overcome physical barriers and increase their selectivity. In this study, we
      propose the use of calcium phosphate as a potential encapsulant or photodynamic
      support for photoactive drugs, using hypericin (HY) as a photosensitizer agent.
      The self-combustion route was used to synthesize the CP nanostructures. The
      structure and morphology of CP nanoparticles were evaluated via X-ray diffraction
      (XRD), Raman and field-emission scanning electron microscopy (FE-SEM). Phases
      rich in hydroxyapatite and CP beta phase, with granular morphology and an average
      grain size of 42.9 nm were obtained. The encapsulation uptake and the
      interactions between HY and the encapsulated system were evaluated by
      fluorescence spectroscopy and Fourier-transform infrared spectroscopy (FTIR),
      respectively. Approximately 13% of HY was enapsulated per 1 MUg of nanoparticles
      of calcium phosphate. Composites were submitted to in vitro assays of
      cytotoxicity and anti-leishmanial activity. The CP nanoparticles did not affect
      the photodynamic activity of HY. On the contrary they showed antileishmanial
      response.

PMID- 29198760
TI  - Impact of long distance rowing on biological health: A pilot study.
AB  - OBJECTIVES: To determine the impact of long distance rowing (160km, nonstop) on
      standard biological parameters and to study the relation between inflammation,
      myocardial necrosis, lipid profile, heart rate and energy expenditure. METHODS:
      Electrolytes, lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT), high-sensitive
      troponin T (hs-cTnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP),
      were measured on non-fasting venous blood samples collected 8h before and after
      the rowing race on five healthy competitors. Heart rate and energy expenditure
      were measured using sporting self-measurement devices. RESULTS: After 16.5h of
      race, significant increases in median CRP (+25.2mg/l; p=0.04), IL-6 (+1.85pg/ml;
      p=0.04), TNF-alpha (+1.2pg/ml; p=0.04) and NT-proBNP levels (+88.8pg/ml; p=0.04)
      were observed, and a close to significant elevation for hs-cTnT(+6ng/l; p=0.06)
      and PCT (+0.14MUg/l; p=0.07). On the other hand, significant decrease in median
      total cholesterol (-0.5mmol/l; p=0.04), triglycerides (-0.7mmol/l; p=0.04) were
      observed. Furthermore, significant correlations between the maximal heart rate
      reached during the race and CRP (r=0.90; p=0.03), IL-6 (r=0.90; p=0.03), and NT
      proBNP (r=0.90; p=0.03) were observed, whereas no such associations were
      retrieved with median heart rate, the percentage of time passed over 70% of
      maximal heart rate or energy expenditure during the race. There was no
      association between PCT, NT-proBNP, hs-cTnT, inflammatory biomarkers, lipid
      profile or heart rate parameters. CONCLUSIONS: Long distance rowing induces
      inflammation and myocardial strain related to the maximal effort generated during
      the race, but has a favourable effect on lipid profile.

PMID- 29198763
TI  - Antimicrobial Photodynamic Therapy mediated by Photodithazine(r) in the treatment
      of denture stomatitis: A case report.
AB  - Antimicrobial Photodynamic Therapy (aPDT) mediated by Photodithazine(r) (PDZ) has
      shown efficacy in the inactivation of Candida spp. in in vitro and in vivo
      studies. This preliminary study reports five clinical cases of patients with
      denture stomatitis (DS) treated with PDZ-mediated aPDT. Five individuals
      diagnosed with DS were selected and submitted to aPDT 3 times a week for 15 days
      (6 sessions). In each session, 200 mg/L of PDZ gel was applied on the upper
      prostheses and on the palate of the patients for 20 min, then, illuminated by a
      light emitting diode at 660 nm (50 J/cm2). Microbiological samples from
      prostheses and palates were also performed and cultured on Sabouraud Dextrose
      Agar and Blood Agar. The values of colony forming units per milliliter (CFU/mL)
      were determined. Standardized photographs of the palates were taken prior the
      treatment (initial), at the end (final) and until 45 days after the completion of
      treatments. The results demonstrated that the aPDT treatment reduced Candida spp.
      and the total microbiota viability at the end of the treatment. For most
      patients, the CFU/mL values obtained in the last microbiological collection (day
      45) were lower than those found before the treatment (initial). Three patients
      presented clinical resolution of DS (no DS signal) after aPDT treatment. One
      individual demonstrated reduction in palatal inflammation and another one did not
      show improvement in the oral lesion. Recurrence of DS was observed in all
      individuals in the follow-up period. PDZ-mediated aPDT may be a promising
      treatment for DS.

PMID- 29198764
TI  - The effect of photodynamic therapy with talaporfin sodium, a second-generation
      photosensitizer, on oral squamous cell carcinoma: A series of eight cases.
AB  - OBJECTIVE: To assess the effect of photodynamic therapy (PDT) with talaporfin
      sodium, a second-generation photosensitizer, on oral squamous cell carcinoma
      (SCC). METHODS: Eight patients who were diagnosed with oral SCC without any
      metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in
      this study. Biopsies were performed 4-6 weeks after t-PDT. The clinical response
      was evaluated using Response Evaluation Criteria in Solid Tumors. RESULTS:
      Complete response (CR) was achieved in six of eight cases, and two cases showed
      partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one
      of the CR cases 9 months after irradiation. The patient underwent tumor resection
      and no recurrence was found after surgery. The two cases with PR died from the
      cancer despite additional PDT. CONCLUSION: t-PDT is an effective treatment
      strategy for oral SCC. Talaporfin sodium has an advantage with regard to early
      elimination from the body compared with porfimer sodium.

PMID- 29198765
TI  - Increased Pituitary Volumes in Children after Fontan Operation: Congestion in the
      Other Portal Circulation.
AB  - We performed brain magnetic resonance imaging in 40 patients after the Fontan
      procedure and 40 control subjects. Pituitary volumes in patients after Fontan
      were significantly larger than those in the control subjects (472 [425-527] vs
      257 [182-311]; P < .0001), and were significantly related to central venous
      pressure.

PMID- 29198766
TI  - The Adolescent Champion Model: Primary Care Becomes Adolescent-Centered via
      Targeted Quality Improvement.
AB  - OBJECTIVE: To evaluate the effects of implementing the Adolescent Champion model,
      a novel quality improvement program targeted at helping primary care sites become
      more adolescent-centered. STUDY DESIGN: Nine primary care sites from pediatrics,
      family medicine, and medicine-pediatrics implemented the Adolescent Champion
      model. Each site identified a multidisciplinary champion team to undergo training
      on adolescent-centered care, deliver prepackaged trainings to other staff and
      providers, make youth-friendly site changes, implement a standardized flow to
      confidentially screen for risky behaviors, and complete a quality improvement
      project regarding confidentiality practices. Adolescent patients, staff, and
      providers were surveyed at baseline, year-end, and 1-year follow-up to assess
      changes. RESULTS: Adolescent patients' experiences with both their provider and
      the site overall significantly improved (P values from <.0001 to .004, N = 474
      baseline, 386 year-end). Staff perceived an improvement in clinic practices
      relating to adolescents and in their ability to make institutional and personal
      change (P < .0001, N = 121 baseline, 109 year-end). The majority of changes were
      sustained 1-year postintervention. Frequently noted site improvements included:
      (1) initiating a method to gather feedback from adolescent patients; (2) adding
      trainings on confidentiality, cultural humility, and using a nonjudgmental
      approach; (3) updating immunizations at every visit; and (4) training providers
      in long acting reversible contraception via implant training. CONCLUSIONS:
      Implementing the Adolescent Champion model successfully helped primary care sites
      become more adolescent-centered. Further studies are needed to evaluate the
      effects of this model on patient outcomes.

PMID- 29198767
TI  - Ultrasonographic Quantitative Analysis of Fatty Pancreas in Obese Children: Its
      Correlation with Metabolic Syndrome and Homeostasis Model Assessment of Insulin
      Resistance.
AB  - OBJECTIVES: To evaluate pancreatic echogenicity on transabdominal ultrasonography
      and the correlation of fatty pancreas with metabolic syndrome (MetS), as well as
      insulin resistance (homeostasis model assessment of insulin resistance [HOMA
      IR]). STUDY DESIGN: This retrospective study included 135 obese children and
      adolescents who underwent transabdominal ultrasonography from January 2015 to
      December 2015. Fatty pancreas was quantitatively analyzed using the pancreato
      perihepatic fat index (PPHFI). The correlation between the PPHFI and HOMA-IR was
      analyzed, and multivariate logistic regression analysis was used to determine
      factors that were independently correlated with MetS. Receiver operating
      characteristic curve analysis was performed to determine the best cut-off value
      of the PPHFI for diagnosing MetS. RESULTS: The PPHFI and the HOMA-IR value were
      significantly higher in subjects with MetS than in those without MetS (P <
      .0001). The PPHFI also showed an association with the HOMA-IR value (r = 0.70; P
      <.0001). The PPHFI was an independent factor for diagnosing MetS (OR 4.36; P =
      .032). The best cut-off value for the PPHFI for a diagnosis of MetS was 2.34 with
      a sensitivity of 0.96 and specificity 0.70. CONCLUSIONS: These results suggest
      that an increased PPHFI is significantly correlated with MetS and insulin
      resistance, and that the PPHFI may be a useful indicator for diagnosing MetS in
      obese children and adolescents. The impact of the presence of fatty pancreas in
      obese children and adolescents must be evaluated.

PMID- 29198768
TI  - Combination oral and mechanical bowel preparations decreases complications in
      both right and left colectomy.
AB  - BACKGROUND: Before elective colectomy, many advocate mechanical bowel preparation
      with oral antibiotics, whereas enhanced recovery pathways avoid mechanical bowel
      preparations. The optimal preparation for right versus left colectomy is also
      unclear. We sought to determine which strategy for bowel preparation decreases
      surgical site infection (SSI) and anastomotic leak (AL). METHODS: Elective
      colectomies from the National Surgical Quality Improvement Program colectomy
      database (2012-2015) were divided by (1) type of bowel preparation: no
      preparation (NP), mechanical preparation (MP), oral antibiotics (PO), or
      mechanical and oral antibiotics (PO/MP); and (2) type of colonic resection:
      right, left, or segmental colectomy. Univariate and multivariate analyses
      identified predictors of SSI and AL, and their risk-adjusted incidence was
      determined by logistic regression. RESULTS: When analyzed as the odds ratio
      compared with NP, the PO and PO/MP groups were associated with a decrease in SSI
      (PO = 0.70 [0.55-0.88] and PO/MP = 0.47 [0.42-0.53]; P < .01). Use of PO/MP was
      associated with a decrease in SSI across all types of resections (right colectomy
      = 0.40 [0.33-0.50], left colectomy = 0.57 [0.47-0.68], and segmental colectomy =
      0.43 (0.34-0.54); P < .01). Similarly, use of PO/MP was associated with a
      decrease in AL in left colectomy = 0.50 ([0.37-0.69]; P < .01) and segmental
      colectomy = 0.53 ([0.36-0.80]; P < .01). CONCLUSION: Mechanical bowel preparation
      with oral antibiotics is the preferred preoperative preparation strategy in
      elective colectomy because of decreased incidence of SSI and AL.

PMID- 29198769
TI  - Subtyping of primary aldosteronism with adrenal vein sampling: Hormone- and side
      specific effects of cosyntropin and metoclopramide.
AB  - BACKGROUND: Cosyntropin and metoclopramide can affect the subtyping of primary
      aldosteronism when used with adrenal vein sampling by exerting hormone- and side
      specific effects on cortisol and aldosterone secretion. We investigated how these
      stimuli affect the selectivity index, the relative aldosterone secretion index,
      and the lateralization index in consecutive primary aldosteronism patients
      submitted to adrenal vein sampling. METHODS: We recruited 171 patients; of these,
      149 underwent adrenal vein sampling before and after stimulation with cosyntropin
      (250 ug intravenous bolus, n= 53, 73% with an aldosterone-producing adenoma) or
      with metoclopramide (10 mg intravenous bolus, n= 96, 65% aldosterone-producing
      adenoma), and 32 with an aldosterone-producing adenoma were investigated for the
      relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine
      (serotonin) 4 receptor with microarrays. Cosyntropin increased the selectivity
      index similarly on both sides; metoclopramide did not. Cosyntropin decreased
      relative aldosterone secretion index on the aldosterone-producing adenoma side
      but not contralaterally. Metoclopramide did not affect the selectivity index, but
      increased the relative aldosterone secretion index similarly on both sides.
      Because of these changes, cosyntropin decreased the lateralization index, while
      metoclopramide did not affect it. The relative gene expression of melanocortin 2,
      albeit heterogeneous across tumors, was 35% less (P<.0001) in aldosterone
      producing adenoma than in the normal adrenal cortex, while dopamine receptor D2
      and 5-hydroxytryptamine (serotonin) 4 receptors did not differ between tissues.
      CONCLUSION: Cosyntropin, while facilitating ascertainment of selectivity, lessens
      the lateralization, likely because of a blunted melanocortin 2 expression in
      aldosterone-producing adenoma. The similar expression of dopamine and 5
      hydroxytryptamine (serotonin) 4 receptors in aldosterone-producing adenoma and
      the normal adrenal cortex can explain why metoclopramide increased the relative
      aldosterone secretion index on both sides and, therefore, failed to increase the
      lateralization index.

PMID- 29198771
TI  - Discussion.

PMID- 29198770
TI  - Preoperative enteral access is not necessary prior to multimodality treatment of
      esophageal cancer.
AB  - BACKGROUND: Surgical enteral access prior to multimodality treatment for
      esophageal cancer is controversial as dysphagia is often used for feeding tube
      referral. We hypothesized that enteral access before neoadjuvant chemoradiation
      for esophageal cancer provides no benefit compared to that placed during
      definitive esophagectomy. METHODS: Patients undergoing esophagectomy for
      esophageal malignancy from 2007 - 2014 were retrospectively identified.
      Clinicopathologic factors were recorded including preoperative enteral access,
      weight change, nutritional laboratory works, and perioperative complications.
      RESULTS: Of 156 identified patients, 99 (63.5%) received neoadjuvant
      chemoradiation and comprised the study cohort. Fifty (50.5%) underwent enteral
      access (gastrostomy [14], jejunostomy [32], other [4]; "Access Group") prior to
      chemoradiation followed by esophagectomy and were compared to 49 "No-Access"
      patients who underwent enteral access during esophagectomy. Clinicopathologic
      variables were similar between cohorts. The Access and No-Access cohorts had
      similar reported dysphagia (86% vs 75.5%, respectively; P = .2) and mean
      preesophagectomy serum albumin (3.9 vs 4 gm/dL, respectively; P = .2). Weight
      loss +/- 6-month periesophagectomy was similar between access versus No-Access
      cohorts (-11.2% vs -15.4%, respectively; P = .1). Weight loss during this period
      was likewise similar for patients with dysphagia in the Access (-11%) versus No
      Access group (-15.2%, P = .1). No difference in complication rates was noted
      between Access (64%) and No-Access groups (51%, P = .2). CONCLUSION: Despite
      healthcare provider bias, there seems to be no nutritional or perioperative
      benefit for enteral access before neoadjuvant chemoradiation for esophageal
      malignancy. Patients with esophageal malignancy should therefore proceed to
      appropriate neoadjuvant and surgical therapy with enteral access performed during
      definitive resection or reserved for those with frank obstruction on endoscopy.

PMID- 29198772
TI  - Human Papillomavirus Vaccine-Related Risk Perceptions Do Not Predict Sexual
      Initiation Among Young Women Over 30 Months Following Vaccination.
AB  - PURPOSE: We examined longitudinally the relationship between human papillomavirus
      (HPV) vaccine-related risk perceptions and initiation of sexual activity among
      adolescent women over 30 months after HPV vaccination. METHODS: Participants
      included 91 sexually inexperienced women aged 13-21 years receiving the HPV
      vaccine who completed at least three of five study visits. At every visit,
      participants completed surveys assessing HPV vaccine-related risk perceptions
      (perceived risk of sexually transmitted infections [STIs] other than HPV,
      perceived need for safer sexual behaviors), and sexual initiation. Outcomes were
      sexual initiation and age of sexual initiation. Associations between risk
      perceptions and outcomes were examined using ordered logistic regression models
      for sexual initiation and interval censored survival analyses for age of sexual
      initiation. RESULTS: Mean age at baseline was 14.9 years (standard deviation [SD]
      1.4). Most participants perceived themselves to be at risk of STIs other than HPV
      (mean scale score = 4.0/10; SD 2.1) and perceived a need for safer sexual
      behaviors (mean scale score = 1.5/10; SD 1.5). By 30 months, 65 participants
      (78%) initiated sex. Perceived risk of STIs and perceived need for safer sexual
      behaviors were not associated with sexual initiation or age of sexual initiation.
      Older age at baseline was associated with sooner sexual initiation (p = .02) and
      older age at sexual initiation (p < .001). Results of ordered logistic regression
      and survival analyses were unchanged when controlling for baseline age.
      CONCLUSIONS: HPV vaccine-related risk perceptions were not associated with sexual
      initiation or age of sexual initiation, providing further support that HPV
      vaccine-related risk perceptions are unlikely to lead to riskier sexual
      behaviors.

PMID- 29198773
TI  - Sex- and Age-Dependent Differences in Autonomic Nervous System Functioning in
      Adolescents.
AB  - PURPOSE: We assessed sex- and age-dependent differences in a cross-sectional
      analysis of cardiac autonomic nervous system (ANS) regulation during sleep in
      adolescents. METHODS: Nocturnal heart rate (HR) and heart rate variability (HRV)
      metrics, reflecting ANS functioning, were analyzed across the night and within
      undisturbed rapid eye movement (REM) and non-REM sleep in 149 healthy adolescents
      (12-22 years; 67 female) from the National Consortium on Alcohol and
      Neurodevelopment in Adolescence. RESULTS: Nocturnal HR was slower in older, more
      pubertally advanced boys than in younger boys. In girls, HR did not vary
      according to age or maturity, although overall HRV and vagal modulation declined
      with age. Although younger boys and girls had similar HR, the male-female HR
      difference increased by ~2.4 bpm every year (p < .01, higher in older girls).
      Boys and girls showed expected increases in total HRV across the night but this
      within-night "recovery" was blunted in girls compared with boys (p < .05). Also,
      the non-REM and REM difference in HR was greater in girls (p < .01). Models
      exploring a role of covariates (sleep, mood, reproductive hormones, activity) in
      influencing HR and HRV showed few significant effects, apart from sedentary
      activity (higher in older girls), which partially mediated the sex * age
      interaction in HR. CONCLUSIONS: Sex-related differences in cardiac ANS function
      emerge during adolescence. The extent to which sex-age divergences in ANS
      function are adaptive or reflect underlying sex-specific vulnerability for the
      development of psychopathology and other health conditions in adolescence needs
      to be determined.

PMID- 29198774
TI  - Serum melatonin levels during the first seven days of severe sepsis diagnosis are
      associated with sepsis severity and mortality.
AB  - OBJECTIVE: Higher serum melatonin levels have previously been found in patients
      with severe sepsis who died within 30 days of diagnosis than in survivors. The
      objective of our study were to determine whether serum melatonin levels during
      the first seven days of severe sepsis diagnosis could be associated with sepsis
      severity and mortality. METHODS: Multicentre study in eight Spanish Intensive
      Care Units which enrolled 308 patients with severe sepsis. We determined serum
      levels of melatonin, malondialdehyde (as biomarker of lipid peroxidation) and
      tumor necrosis factor-alpha at days 1, 4 and 8 of severe sepsis diagnosis. The
      study's primary endpoint was 30-day mortality. RESULTS: A total of 103 patients
      had died and 205 survived at 30 days of severe sepsis diagnosis, with the non
      survivors presenting higher serum melatonin levels at days 1 (p<0.001), 4
      (p<0.001) and 8 (p<0.001) of severe sepsis diagnosis than the survivor patient
      group. The multiple logistic regression analysis found that serum melatonin
      levels at days 1, 4 and 8 of severe sepsis diagnosis (p<0.001, p=0.01 and
      p=0.001, respectively) were associated with mortality adjusted for age, serum
      lactic acid, SOFA score and diabetes mellitus. CONCLUSIONS: The novel and more
      interesting findings of our study were that serum melatonin levels during the
      first seven days of severe sepsis diagnosis are associated with sepsis severity
      and mortality.

PMID- 29198775
TI  - Dynamic miRNA-mRNA regulations are essential for maintaining Drosophila immune
      homeostasis during Micrococcus luteus infection.
AB  - Pathogen bacteria infections can lead to dynamic changes of microRNA (miRNA) and
      mRNA expression profiles, which may control synergistically the outcome of immune
      responses. To reveal the role of dynamic miRNA-mRNA regulation in Drosophila
      innate immune responses, we have detailedly analyzed the paired miRNA and mRNA
      expression profiles at three time points during Drosophila adult males with
      Micrococcus luteus (M. luteus) infection using RNA- and small RNA-seq data. Our
      results demonstrate that differentially expressed miRNAs and mRNAs represent
      extensively dynamic changes over three time points during Drosophila with M.
      luteus infection. The pathway enrichment analysis indicates that differentially
      expressed genes are involved in diverse signaling pathways, including Toll and
      Imd as well as orther signaling pathways at three time points during Drosophila
      with M. luteus infection. Remarkably, the dynamic change of miRNA expression is
      delayed by compared to mRNA expression change over three time points, implying
      that the "time" parameter should be considered when the function of miRNA/mRNA is
      further studied. In particular, the dynamic miRNA-mRNA regulatory networks have
      shown that miRNAs may synergistically regulate gene expressions of different
      signaling pathways to promote or inhibit innate immune responses and maintain
      homeostasis in Drosophila, and some new regulators involved in Drosophila innate
      immune response have been identified. Our findings strongly suggest that miRNA
      regulation is a key mechanism involved in fine-tuning cooperatively gene
      expressions of diverse signaling pathways to maintain innate immune response and
      homeostasis in Drosophila. Taken together, the present study reveals a novel role
      of dynamic miRNA-mRNA regulation in immune response to bacteria infection, and
      provides a new insight into the underlying molecular regulatory mechanism of
      Drosophila innate immune responses.

PMID- 29198776
TI  - Insect C-type lectins in innate immunity.
AB  - C-type lectins (CTLs) are a family of proteins that contain characteristic
      modules of carbohydrate-recognition domains (CRDs) and they possess the binding
      activity to ligands in a calcium-dependent manner. CTLs play important roles in
      animal immune responses, and in insects, they are involved in opsonization,
      nodule formation, agglutination, encapsulation, melanization, and
      prophenoloxidase activation, as well as in maintaining gut microbiome
      homeostasis. In this review, we will summarize insect CTLs, compare the
      properties of insect CTLs with vertebrate CTLs, and focus mainly on the domain
      organization and functions of insect CTLs in innate immunity.

PMID- 29198777
TI  - The cyclin-dependent kinase 2 (CDK2) mediates hematopoiesis through G1-to-S
      transition in Chinese mitten crab Eriocheir sinensis.
AB  - Cyclin-dependent kinases (CDKs), a family of cell cycle-related serine/threonine
      kinases, participate in various biological processes, and play crucial roles in
      the innate immunity. In the present study, a CDK2 (designed as EsCDK2) with a
      serine/threonine protein kinase catalytic domain was identified from Chinese
      mitten crab (Eriocheir sinensis). The full-length cDNA sequence of EsCDK2 was of
      2405 bp with an open reading frame (ORF) of 909 bp. EsCDK2 shared 66%-81%
      sequence similarities with previously identified CDK2s. It was clustered with the
      CDK2 from Penaeus monodon in the invertebrate branch of the phylogenetic tree.
      The mRNA transcripts of EsCDK2 were highly expressed in hematopoietic tissue
      (HPT) and gonad, while lower in hemocytes, heart, gills, and muscle. EsCDK2
      protein distributed in both cytoplasm and nucleus of HPT cells. The expression of
      EsCDK2 mRNA in HPT was significantly up-regulated and peaked at 3 h post
      stimulations with Aeromonas hydrophila (2.31-fold, p < 0.05) and
      Lipopolysaccharide (LPS) (2.02-fold, p < 0.05). After exsanguination, the total
      hemocyte counts (THC) decreased significantly to 0.42 * 107/ml (0.39-fold, p <
      0.05) at 0.5 h, then returned to a normal level at 6 h, while the mRNA expression
      of EsCDK2 in HPT cells was up-regulated at the early phase from 0.5 h to 6 h.
      After injection of EsCDK2-dsRNA, the mRNA expression level of EsCDK2 in HPT and
      THC both decreased to 0.53-fold (p < 0.01) and 0.78-fold (p < 0.05) at 24 h,
      respectively, and the percentage of new-born hemocytes in HPT also decreased
      significantly from 37.7% to 16.3% (0.43-fold, p < 0.01). After knocking down of
      EsCDK2, THC decreased dramatically at 6 h (0.65-fold, p < 0.01) post
      exsanguination, while returned normal at 6 h in PBS group. After interference of
      EsCDK2 mRNA expression, the percentage of G0-G1 phase cells significantly
      increased to 85.01% (1.26-fold, p < 0.01), while S phase and G2-M phase cells
      significantly decreased to 7.92% (0.46-fold, p < 0.01) and 7.07% (0.43-fold, p <
      0.01) respectively, indicating that the cell cycle of HPT cells arrested at G1
      phase. These results collectively demonstrated that EsCDK2 participated in the
      regeneration of hemocytes or hematopoiesis by regulating the transition from G1
      to S phase in the cell cycle, and involves in the innate immune responses of E.
      sinensis.

PMID- 29198778
TI  - Dilated Cardiomyopathy With Short QT Interval Suggests Primary Carnitine
      Deficiency.

PMID- 29198779
TI  - Mitotic rate is associated with positive lymph nodes in patients with thin
      melanomas.
AB  - BACKGROUND: The American Joint Commission on Cancer will remove mitotic rate from
      its staging guidelines in 2018. OBJECTIVE: Using a large nationally
      representative cohort, we examined the association between mitotic rate and lymph
      node positivity among thin melanomas. METHODS: A total of 149,273 thin melanomas
      in the National Cancer Database were examined for their association of high-risk
      features of mitotic rate, ulceration, and Breslow depth with lymph node status.
      RESULTS: Among 17,204 patients with thin melanomas with data on Breslow depth,
      ulceration, and mitotic rate who underwent a lymph node biopsy, there was a
      strong linear relationship between odds of having a positive lymph node and
      mitotic rate (R2 = 0.96, P < .0001, beta = 3.31). The odds of having a positive
      node increased by 19% with each 1-point increase in mitotic rate (odds ratio,
      1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean
      mitotic rate of 1.54 plus or minus 2.07 mitoses/mm2 compared with 3.30 plus or
      minus 3.54 mitoses/mm2 for those with positive nodes (P < .0001). LIMITATIONS:
      The data collected do not allow for survival analyses. CONCLUSIONS: Mitotic rate
      was strongly associated with the odds of having a positive lymph node and should
      continue to be reported on pathology reports.

PMID- 29198780
TI  - Pemphigus and hematologic malignancies: A population-based study of 11,859
      patients.
AB  - BACKGROUND: The association of nonparaneoplastic pemphigus with comorbid
      hematologic malignancies has yet to be established. OBJECTIVE: To estimate the
      association between pemphigus and the common types of hematologic malignancies.
      METHODS: A cross-sectional study was conducted comparing pemphigus patients with
      age-, sex- and ethnicity-matched control subjects regarding the prevalence of 6
      comorbid hematologic malignancies. The study was performed using the computerized
      database of Clalit Health Services ensuring the availability of 4.5 million
      patients. RESULTS: The study included 1985 pemphigus patients and 9874 control
      subjects. The prevalence of chronic leukemia (0.9% vs 0.4%, odds ratio [OR] 2.1,
      95% confidence interval [CI] 1.2-3.6), multiple myeloma (0.8% vs 0.4%, OR 2.2,
      95% CI 1.2-3.9), and non-Hodgkin lymphoma (1.8% vs 1.2%, OR 1.5, 95% CI 1.0-2.2)
      was greater in patients with pemphigus than in controls. The association with
      chronic leukemia remained significant following the adjustment for
      immunosuppressive therapy (adjusted OR 2.0, 95% CI 1.1-3.7). No significant
      associations were observed between pemphigus and acute leukemia, Hodgkin
      lymphoma, myelodysplastic syndrome, and polycythemia vera. LIMITATIONS: Lack of
      immunopathologic validation of the diagnosis of pemphigus. CONCLUSION: A
      significant association was observed between pemphigus and chronic leukemia,
      multiple myeloma, and non-Hodgkin lymphoma. Further research is warranted to
      establish this observation in other cohorts.

PMID- 29198782
TI  - Split-thickness skin graft strips obtained with DermaBlade to cover large
      surgical defects on scalp.

PMID- 29198781
TI  - Effectiveness of low-level laser therapy in lichen planopilaris.

PMID- 29198783
TI  - Common Child and Adolescent Cutaneous Infestations and Fungal Infections.
AB  - Cutaneous infections and infestations are common among children and adolescents.
      Ectoparasitic infestations affect individuals across the globe. Head lice, body
      lice, scabies, and infestations with bed bugs are seen in individuals who reside
      in both resource poor areas and in developed countries. Superficial cutaneous and
      mucosal candida infections occur throughout the life cycle. Dermatophyte
      infections of keratin-containing skin and skin structures result in tinea capitis
      (scalp), tinea corporis (body), tinea pedis (foot), and tinea unguium (nails).
      Less frequent endemic fungal infections such as blastomycosis, coccidiodomycosis,
      and histoplasmosis may present with skin findings. This article will describe the
      epidemiology and transmission of these conditions as well as their clinical
      manifestations. The approach to diagnosis will be addressed as well as primary
      prevention and current therapies.

PMID- 29198784
TI  - Pathogenesis of tuberculosis and other mycobacteriosis.
AB  - The evolution between Mycobacterium tuberculosis infection and active
      tuberculosis is multifactorial and involves different biological scales. The
      synthesis of ESAT-6 or the induction of alveolar macrophage necrosis are key, but
      to understand it, it is necessary to consider the dynamics of endogenous and
      exogenous reinfection, drainage of lung parenchyma and respiratory mechanics,
      local fibrosis processes and blood supply. Paradoxically, the immune response
      generated by the infection is highly protective (90%) against active
      tuberculosis, although as it is essentially based on the proliferation of Th1
      lymphocytes, it cannot prevent reinfection. Severe immunosuppression can only
      explain 10% of active tuberculosis cases, while the remainder are attributable to
      comorbidities, a proinflammatory environment and an unknown genetic propensity.
      The pathogenic capacity of environmental mycobacteria is discrete, linked to
      deficits in the innate and acquired immune response. The ability to generate
      biofilms and the ability of M. ulcerans to generate the exotoxin mycolactone is
      remarkable.

PMID- 29198785
TI  - The distribution of tritium in aquatic environments, Lithuania.
AB  - The aim of this study is to investigate mobile radionuclide tritium (3H or T)
      activity dynamics in aquatic environments related to Ignalina NPP (INPP) site and
      water bodies located in remote areas unaffected by the INPP. The 3H excess in the
      INPP environment was analyzed and compared to the variable 3H background level
      over the period of operation of the INPP (end of 1983 - end of 2009) and during
      the initial stage of decommissioning (2010-2017). 3H in the INPP vicinity has
      been studied in the water of artificial channels related to operation of the INPP
      and site drainage, in natural surface water bodies and, at a smaller scale, in
      unconfined groundwater. This study presents an extensive 3H data set extending
      back to 1980, i.e. before INPP operation started. To assess the contribution of
      global sources to 3H dynamics, monthly precipitation was also studied, along with
      water from the Baltic Sea, Curonian Lagoon and Nemunas River were studied as
      well, all three of these located in the Lithuanian maritime zone. The 3H activity
      concentration in water was measured using liquid scintillation counting (LSC)
      techniques (direct counting and counting after enrichment). During the period of
      INPP operation, 3H from liquid effluent could be clearly observed in discharge
      channels, occurring in rather low diluted conditions, as well as in Lake
      Druksiai, the cooling basin, at an even more diluted level. The highest 3H
      activity concentration in Lake Druksiai was observed in 2003 and reached 201.3 +/
      1.3 TU at a time when 3H activity concentrations in background water bodies was
      9.2 +/- 3.5 TU. After the closure of the INPP, the 3H liquid effluent rate
      reduced by approximately two orders of magnitude (from 1012 Bq in 1991 to 1010 Bq
      in 2016) and when decommissioning activity commenced then the 3H activity
      concentration fell to that approaching the background level (19-27 TU) that can
      still be observed in industrial discharge and rainwater drainage channels. 3H as
      a result of leakage from the INPP can be observed in groundwater only in direct
      proximity to the INPP site near the radioactive waste storage zone.

PMID- 29198786
TI  - The integrated contaminant elution and tracer test toolkit, ICET3, for improved
      characterization of mass transfer, attenuation, and mass removal.
AB  - It is evident based on historical data that groundwater contaminant plumes
      persist at many sites, requiring costly long-term management. High-resolution
      site-characterization methods are needed to support accurate risk assessments and
      to select, design, and operate effective remediation operations. Most subsurface
      characterization methods are generally limited in their ability to provide
      unambiguous, real-time delineation of specific processes affecting mass-transfer,
      transformation, and mass removal, and accurate estimation of associated rates. An
      integrated contaminant elution and tracer test toolkit, comprising a set of local
      scale groundwater extraction-and injection tests, was developed to ameliorate the
      primary limitations associated with standard characterization methods. The test
      employs extended groundwater extraction to stress the system and induce hydraulic
      and concentration gradients. Clean water can be injected, which removes the
      resident aqueous contaminant mass present in the higher-permeability zones and
      isolates the test zone from the surrounding plume. This ensures that the
      concentrations and fluxes measured within the isolated area are directly and
      predominantly influenced by the local mass-transfer and transformation processes
      controlling mass removal. A suite of standard and novel tracers can be used to
      delineate specific mass-transfer and attenuation processes that are active at a
      given site, and to quantify the associated mass-transfer and transformation
      rates. The conceptual basis for the test is first presented, followed by an
      illustrative application based on simulations produced with a 3-D mathematical
      model and a brief case study application.

PMID- 29198787
TI  - Bovine arch anatomy influences recoarctation rates in the era of the extended end
      to-end anastomosis.
AB  - OBJECTIVES: Arch branching has never been shown to influence recoarctation after
      extended end-to-end anastomosis via thoracotomy, yet in each study bovine arch
      identification is grossly underreported. This study aims to (1) assess chart
      review reliability in bovine arch identification; (2) determine recoarctation
      risk with a bovine arch; and (3) explore an anatomic explanation for recurrent
      arch obstruction based on arch anatomy. PATIENTS: A total of 49 consecutive
      patients underwent thoracotomy with extended end-to-end aortic coarctation repair
      at a single institution (2007-2012). METHODS: Echocardiograms from these patients
      were reviewed for arch anatomy and compared with the echocardiographic reports.
      Recurrent arch obstruction was defined as an echocardiographic gradient across
      the repair of 20 mm Hg or greater. For cases with angiographic images (n = 17), a
      scaled clamping distance between the left subclavian artery and the maximal
      proximal clamp location on orthogonal projections was then calculated across arch
      anatomies. RESULTS: Chart review identified 6.1% (3/49) of patients with a bovine
      arch compared with 28.6% (14/49) on targeted image review. A total of 28.6%
      (4/14) of patients with a bovine arch had a follow-up gradient of 20 mm Hg or
      greater. Only 5.7% (2/35) of patients with normal arch branching had a follow-up
      gradient of 20 mm Hg or greater. The mean clamping index was significantly
      diminished in patients with bovine arch anatomy. CONCLUSIONS: Arch anatomy often
      goes undocumented on preoperative imaging, yet children undergoing extended end
      to-end repair with bovine arch anatomy are at a significantly increased risk of
      recoarctation. This may be due to a reduced clampable distance to facilitate
      repair. These results should be considered in the preoperative assessment,
      parental counseling, and surgical approach for children with discrete aortic
      coarctation.

PMID- 29198788
TI  - Designing valves: An art or science?

PMID- 29198789
TI  - Yesterday's heroic measure is now standard procedure: Extracorporeal membrane
      oxygenation as a bridge to lung transplant.

PMID- 29198790
TI  - In the mood.

PMID- 29198791
TI  - Aortic sinus pouch technique for transposition of the great arteries with
      intramural coronary artery.

PMID- 29198792
TI  - Thinking outside the duct.

PMID- 29198793
TI  - Appropriate use: Neither restrictive nor a guideline.

PMID- 29198794
TI  - Heart Team 2.0: Keep your friends close...and your enemy closer!

PMID- 29198795
TI  - Is there still a role for balloon dilatation before transcatheter aortic valve
      replacement-or, indeed, for transaortic access?

PMID- 29198796
TI  - Commentary on the impacts of postoperative complications on survival after lung
      cancer surgery.

PMID- 29198797
TI  - Resection of primary lung cancer with incidental pleural seeding: Seeds of change
      or reap what you sow?

PMID- 29198798
TI  - Dual antiplatelet therapy at discharge: Antiplatelet practice patterns after
      coronary artery bypass grafting, surgical anecdote is driving standard of care.

PMID- 29198799
TI  - To robot or not to robot: Is that really the question?

PMID- 29198800
TI  - Timing of surgery for pulmonary embolism: An evolving paradigm.

PMID- 29198801
TI  - Bicuspid aortic valve-associated aortopathy: A slowly evolving picture.

PMID- 29198802
TI  - Del Nido cardioplegia: A one stop shot for adult cardiac surgery?

PMID- 29198803
TI  - Against the tide.

PMID- 29198804
TI  - Is an aortic tissue valve the best choice for young adults?

PMID- 29198805
TI  - The quality of quality assessment after atrial fibrillation surgery.

PMID- 29198806
TI  - Toronto bridges to successful lung transplantation.

PMID- 29198807
TI  - Use of cutting-edge technology to learn myocardial cutting edge in septal
      myectomy.

PMID- 29198808
TI  - Development of rectal self-emulsifying suspension of a moisture-labile water
      soluble drug.
AB  - Self-emulsifying drug delivery systems, commonly used for oral delivery of poorly
      soluble compounds, were used to formulate water soluble but moisture labile
      compounds for rectal application. The objective was to use the oily phase of the
      system to formulate a liquid, non-aqueous product while obtaining the advantages
      of self-emulsification, rapid contact with the rectal mucosa and rapid absorption
      post-administration. Ceftriaxone was used as a model drug and the human bile salt
      sodium chenodeoxycholate was used as an absorption enhancer. After preliminary
      screening of 23 excipients, based on their emulsification ability and emulsion
      fineness in binary and ternary mixtures, a full factorial design was used to
      screen different formulations of three preselected excipients. The optimal
      formulation contained 60% of excipients, namely Capryol 90, Kolliphor EL and
      Kolliphor PS20 in 4 : 6 : 6 ratio and 40% of a powder blend that included 500 mg
      of ceftriaxone. Characterization of the system showed that it complied with the
      requirements for rectal administration, in particular rapid emulsification in a
      small quantity of liquid. Rabbit bioavailability showed rapid absorption of
      ceftriaxone, achieving 128% bioavailability compared to powder control
      formulation. These results demonstrated the potential of self-emulsifying
      formulations for rectal administration of Class 3 BCS drugs.

PMID- 29198809
TI  - The effect of mechanical dry coating with magnesium stearate on flowability and
      compactibility of plastically deforming microcrystalline cellulose powders.
AB  - Mechanofusion is a dry coating method that can be used to improve the flowability
      of cohesive powder by coating host particles with a lubricant, for example
      magnesium stearate (MgSt). It has been shown previously that fragmenting material
      can under some circumstances be mechanofused with MgSt without impairing
      compactibility of the powder and without reducing the dissolution rate of the
      resulting tablets. However, the effects on material with viscoelastic behaviour,
      known to be sensitive for the negative effects of MgSt, is not known. Therefore,
      mechanofusion of microcrystalline cellulose (MCC) with MgSt was investigated in
      this study. Four MCC grades were mechanofused with different MgSt concentrations
      and process parameters, and the resulting flowability and compactibility were
      studied. Starting materials and low-shear blended binary mixtures were studied as
      a reference. Mechanofusion improved the flow properties of small particle size
      MCC powders (d50 < 78 MUm) substantially, but increasing the MgSt content
      consequently resulted in weaker tablets. Larger particle size MCC grades,
      however, fractured under the shear forces during the mechanofusion process and
      hence their flow properties were decreased. Improvement of the flow properties
      but also the negative effects on compactibility of small particle size grades
      were observed even at relatively mild mechanofusion parameters and low lubricant
      concentrations.

PMID- 29198810
TI  - Short-duration ocular iontophoresis of ionizable aciclovir prodrugs: A new
      approach to treat herpes simplex infections in the anterior and posterior
      segments of the eye.
AB  - The objective was to investigate (trans)corneal and transscleral iontophoresis of
      biolabile amino acid ester prodrugs of aciclovir (ACV-X, X = Arg, Gly and Trp) as
      a means to increase ocular bioavailability of ACV. Prodrugs displayed tissue
      dependent susceptibility to hydrolysis. Iontophoresis of ACV-Arg, ACV-Gly and ACV
      Trp (5 mM, 0.5 mA/cm2) for 5 min followed by 55 min passive diffusion resulted in
      appreciable corneal deposition (21.5 +/- 5.1, 14.1 +/- 2.0 and 5.3 +/- 0.6
      nmol/cm2, respectively) and transcorneal permeation (13.9 +/- 1.6, 10.9 +/- 1.8
      and 5.7 +/- 0.5 nmol/cm2, respectively) of ACV species. In contrast, passive
      delivery of ACV across porcine cornea after 1 h was < LOQ (i.e. <0.125 nmol/cm2).
      Transscleral permeation of ACV-Arg, ACV-Gly and ACV-Trp (9 mM, 1.25 mA/cm2) after
      iontophoresis for 5 min was 20.4 +/- 3.8, 12.3 +/- 0.3 and 8.4 +/- 0.4 nmol/cm2,
      respectively - far superior to passive delivery which was again < LOQ. Using
      intact porcine eye globes, 5 min transscleral iontophoresis of ACV-Gly at 3.75
      mA/cm2 resulted in considerable delivery of ACV species to the choroid/retina and
      vitreous humour (5.7 +/- 2.3 and 11.7 +/- 3.7 nmol/cm2, respectively).
      Furthermore, the average concentration of ACV species in the whole eyeball (4.5
      +/- 1.6 nmol/cm3) was significantly higher than the IC50 of ACV against HSV-1
      (<0.22 nmol/cm3), demonstrating the potential application for the treatment of
      ocular HSV infections.

PMID- 29198812
TI  - The effect of a radial neck notch on press-fit stem stability: a biomechanical
      study on 7 cadavers.
AB  - BACKGROUND: Minimal micromotion is necessary for osteointegration of cementless
      radial head prostheses. When radial head fractures extend longitudinally, where
      the neck cut for prosthetic replacement should be made is uncertain. We
      hypothesized that complete resection of the notched portion of a radial neck
      confers no advantage in initial stability compared with not resecting the defect
      and inserting the implant into a notched radial neck. MATERIALS AND METHODS: The
      radii of 7 cadavers underwent radial head resection and implantation with a 25-mm
      long press-fit radial head stem. Before implantation, a 5-mm-long notch that was
      less than 1-mm wide was made in the radial neck. After the stem-bone micromotion
      was recorded, the proximal 5 mm of radial neck, incorporating the entire notch,
      was cut away, the stem was inserted 5 mm further, and the resulting micromotion
      was recorded. RESULTS: The mean micromotion measured in the presence of a
      cortical notch was 51 +/- 6 um. After the neck was circumferentially cut and the
      stem was advanced, the micromotion (46 +/- 9 um) was not statistically
      significantly different. DISCUSSION: Initial stability of an adequately sized
      cementless stem in the presence of a 5-mm-long cortical notch was well within the
      threshold needed for bone ingrowth (<100 um). In addition, there was no reduction
      of micromotion after the notch-containing portion of the radial neck was resected
      and the stem was advanced. Making a neck cut distal to a 5-mm-long, 1-mm-wide
      cortical notch does not confer added stability. Thus, surgeons can preserve bone
      stock and avoid an aggressive neck cut.

PMID- 29198811
TI  - Preparation of PEGylated liposomes incorporating lipophilic lomeguatrib
      derivatives for the sensitization of chemo-resistant gliomas.
AB  - Liposomal delivery is a well-established approach to increase the therapeutic
      index of drugs, mainly in the field of cancer chemotherapy. Here, we report the
      preparation and characterization of a new liposomal formulation of a derivative
      of lomeguatrib, a potent O6-methylguanine-DNA methyltransferase (MGMT)
      inactivator. The drug had been tested in clinical trials to revert
      chemoresistance, but was associated with a low therapeutic index. A series of
      lomeguatrib conjugates with distinct alkyl chain lengths - i.e. C12, C14, C16,
      and C18 - was synthesized, and the MGMT depleting activity as well as
      cytotoxicity were determined on relevant mouse and human glioma cell lines. Drug
      containing liposomes were prepared and characterized in terms of loading and in
      vitro release kinetics. The lipophilic lomeguatrib conjugates did not exert
      cytotoxic effects at 5 MUM in the mouse glioma cell line and exhibited a similar
      MGMT depleting activity pattern as lomeguatrib. Overall, drug loading could be
      improved by up to 50-fold with the lipophilic conjugates, and the slowest leakage
      was achieved with the C18 derivative. The present data show the applicability of
      lipophilic lomeguatrib derivatization for incorporation into liposomes, and
      identify the C18 derivative as the lead compound for in vivo studies.

PMID- 29198813
TI  - Preface.

PMID- 29198814
TI  - A high content imaging flow cytometry approach to study mitochondria in T cells:
      MitoTracker Green FM dye concentration optimization.
AB  - Mitochondria, the powerhouse of the cell, are known to remodel their membrane
      structures through the process of fusion or fission. Studies have indicated that
      T cells adopt different energy metabolic phenotypes, namely oxidative
      phosphorylation and glycolysis depending on whether they are naive, effector and
      memory T cells. It has recently been shown that changes in mitochondrial
      morphology dictate T cell fate via regulation of their metabolism. Our keen
      interest in T cell function and metabolism led us to explore and establish a
      method to study mitochondria in live T cells through a novel high content
      approach called Imaging Flow Cytometry (IFC). The focus of our current study was
      on developing a protocol to standardize the concentration of MitoTracker Green FM
      dye to observe mitochondria in live T cells using IFC. We began the study by
      using widefield microscopy to confirm the localisation of MitoTracker Green FM
      labelled mitochondria in live T cells. This was followed by testing various
      concentrations of the dye to achieve a similar labelling pattern using IFC while
      eliminating false positive or negative staining. The optimization of the method
      used to label the mitochondria by IFC for analysis included standardisation of a
      number of important parameters such as dye concentration, voltage, fluorescence
      intensity values for acquisition and processing. IFC could potentially be a
      powerful method to study T cells in a relatively high throughput manner.

PMID- 29198815
TI  - Voice Profile Recovery and Quality of Life Changes After Microdirect Laryngoscopy
      in Three Categories of Glottis Lesions: Benign, Precancerous, and Malignant.
AB  - The aim of the study was comparison of voice and life quality after microdirect
      laryngoscopy in three patient histopathological categories: benign, precancerous,
      and malignant glottic lesions. A totalnof 137 patients treated with microdirect
      laryngoscopy were included in the study. Each patient was evaluated with a
      multidimensional protocol before and 3, 6, and 12 months after treatment. Final 1
      year evaluations were achieved in 74.5% (102). The assessment included
      laryngovideostroboscopy (LVS), perceptual (GRBAS) grading, aerodynamic measures
      including maximum phonation time and phonation quotient and acoustic measurements
      (Kay Elemetrics Multi-Speech program), Voice Handicap Index (VHI), Voice-Related
      Quality of Life questionnaire; and World Health Organization Quality of Life
      Scale-Brief Version (WHOQoL-BREF). An improvement in mean value of LVS ratings
      was obtained in all three groups; however, only in benign lesion group was it
      consistently statistically significant for each time period (P < 0.001).
      Perceptual evaluation revealed significant improvement of G, R, and B parameters
      in benign lesions for each time period. In malignant neoplasms R and B parameters
      improved 3 and 6 months post microsurgery. In patients with benign lesions the
      maximum phonation time increased, but the improvement was significant only after
      3 months. The acoustic parameters improved in all three groups. VHI significantly
      improved in patients with benign lesions after 3 and 12 months. VHI in the
      malignant neoplasm group significantly worsened on the first follow-up visit.
      Considering quality of life (QoL) results, only in patients with benign lesions
      was there a significant improvement in overall assessment of their QoL and
      general health.

PMID- 29198816
TI  - Association between race/ethnicity and disability status and receipt of vaccines
      among older adults in Florida.
AB  - BACKGROUND: Individuals living with a disability or are a member of a certain
      racial/ethnic group may be at heightened risk for not receiving important
      vaccinations. OBJECTIVE: This study examined whether race/ethnicity and
      disability status are associated with the receipt of two vaccines (influenza and
      pneumococcal) among older adults living in Florida. METHODS: Using the 2011-2015
      Florida Behavioral Risk Factor Surveillance System, a cross-sectional survey, we
      ran bivariate and multivariate analyses to determine the associations for
      race/ethnicity and disability status with receipt of vaccinations among
      individuals 65 years and older. Interactions between race/ethnicity and
      disability status were tested in each model. RESULTS: Among our study sample, 68%
      received the pneumococcal vaccine in their lifetime and 54% of them received
      influenza vaccine in the past 12 months. Multivariate logistic regression
      indicated that Non-Hispanic Blacks and Hispanics were less likely to receive both
      vaccines compared to Non-Hispanic Whites. Older adults with a disability were
      more likely to receive influenza and pneumococcal vaccines compared to those
      without. A significant interaction was observed between race/ethnicity and
      disability status for predicting pneumococcal vaccination receipt. CONCLUSIONS:
      Large proportions of older adults in Florida continue to go without needed
      vaccinations. Although race/ethnicity and disability status were shown to have
      some association with receipt of vaccines, having a regular source of care,
      employment and income also were shown to be important predictors.

PMID- 29198818
TI  - Comparison of General Anesthesia and Conscious Sedation During Computed
      Tomography-Guided Radiofrequency Ablation of T1a Renal Cell Carcinoma.
AB  - PURPOSE: Percutaneous radiofrequency ablation is so painful that this treatment
      requires pain control such as conscious sedation or general anesthesia. It is
      still unclear which type of anesthesia is better for treatment outcomes of renal
      cell carcinoma. This study aimed to compare general anesthesia and conscious
      sedation in treating patients with renal cell carcinoma with radiofrequency
      ablation. METHODS: Between 2010 and 2015, 51 patients with biopsy-proven renal
      cell carcinomas (<4 cm) were treated with computed tomography-guided
      radiofrequency ablation. General anesthesia was performed in 41 and conscious
      sedation was performed in 10 patients. Tumour size, local tumour progression,
      metastasis, major complication, effective dose, glomerular filtration rate
      difference, and recurrence-free survival rate were compared between these groups.
      RESULTS: The mean tumour size was 2.1 cm in both groups (P = .673). Local tumour
      progression occurred in 0% (0 of 41) of the general anesthesia group, but in 40%
      (4 of 10) of the conscious sedation group (P = .001). Metastases in these groups
      occurred in 2.4% (1 of 41) of the general anesthesia group and 20% (2 of 10) of
      the conscious sedation group (P = .094). No major complications developed in
      either group after the first radiofrequency ablation session. The mean effective
      doses in these groups were 21.7 mSv and 21.2 mSv, respectively (P = .868). The
      mean glomerular filtration rate differences in the general anesthesia and
      conscious sedation groups were -13.5 mL/min/1.73 m2 and -19.1 mL/min/1.73 m2,
      respectively (P = .575). Three-year recurrence-free survival rates in these
      groups were 97.6% and 60.0%, respectively (P = .001). CONCLUSIONS: General
      anesthesia may provide better intermediate outcomes than conscious sedation in
      treating small renal cell carcinomas with radiofrequency ablation.

PMID- 29198817
TI  - Whole specimen intraoperative frozen section analysis. Experience with 1082 basal
      cell carcinomas.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) excised leaving positive tumour margins,
      are at a higher risk of recurrence. Accordingly, complete tumour removal with
      preservation of healthy tissue, aiming for low recurrence rates, is the main goal
      in treating BCCs. OBJECTIVE: The present study aimed to identify the reliability
      of the Whole Specimen Intraoperative Frozen Section Analysis (WIFSA) technique by
      comparing intraoperative WIFSA and postoperative Formalin-Fixed Paraffin-Embedded
      section analysis (FFPE) results in 1082 basal cell carcinomas and by assessing
      the recurrence rates during a follow-up period up to 10 years. METHODS: A single
      centre retrospective cohort of all patients with BCC of the face receiving
      surgical excision with the WIFSA method between January 2007 and December 2013
      was evaluated. We compared the intraoperative frozen section results with
      postoperative FFPE in order to assess accuracy of the WIFSA. Recurrence rates
      were assessed among all BCCs with a tumour-free margin at final excision that had
      a minimum follow-up of 6 months. RESULTS: A total of 996 patients with 1082 BCCs
      were treated with the WIFSA. Overall agreement of WIFSA with conventional
      postoperative FFPE was 98.8%, sensitivity and specificity being 99.0% and 98.7%
      respectively. We excluded 23 BCCs that still had positive tumour margins at the
      end of the procedure and another 67 for the analysis of recurrence rate because
      follow-up was shorter than 6 months. A total of 992 BCCs with a tumour-free
      margin at final excision had a mean follow-up of 5.6 years (mean 67 +/- 27.7
      months (range 6-117 months)). The total recurrence rate was 2.1% (21 out of 992
      BCCs). The recurrence rate among the primary tumours was 1.6% (13 out of 828
      cases) and 4.9% among the recurring tumours (8 out of 164 cases). CONCLUSION:
      This study indicates that, in patients with primary or recurring BCCs, WIFSA
      provides a high accuracy for intraoperative specimen analysis and has a low
      recurrence rate after a mean follow-up of 5.6 years. FUNDING: This research did
      not receive any specific grant from funding agencies in the public, commercial,
      or not-for-profit sectors.

PMID- 29198819
TI  - A Day in the Life of MRI: The Variety and Appropriateness of Exams Being
      Performed in Canada.
AB  - PURPOSE: This study aimed to determine the volumes and types of magnetic
      resonance imaging exams being performed across Canada, common indications for the
      exams, and exam appropriateness using multiple evaluation tools. METHODS:
      Thirteen academic medical institutions across Canada participated. Data were
      obtained relating to a single common day, October 1, 2014. Patient demographics,
      type by anatomic region and indication for imaging were analysed. Each exam was
      assessed for appropriateness via the Canadian Association of Radiologists
      Referral Guidelines and the American College of Radiology Appropriateness
      Criteria. The Alberta and Saskatchewan spine screening forms and the Alberta knee
      screening form were also used where applicable. The proportion of exams that were
      unscorable, appropriate, and inappropriate was determined. Exam-level results
      were compared between the 2 main evaluation tools. RESULTS: Data were obtained
      for 1087 relevant exams. There were 591 women and 460 men. 36 requisitions did
      not indicate the patient's sex. Brain exams were the most common, comprising
      32.5% of the sample. Cancer was the most common indication. Overall, 87.0%-87.4%
      of the MR exams performed were appropriate; 6.6%-12.6% were inappropriate, based
      on the 2 main evaluation tools. Results differed by anatomic region; spine exams
      had the highest proportion, with nearly one-third of exams deemed inappropriate.
      CONCLUSION: Variations by anatomic region indicate that focused exam request
      evaluation or screening methods could substantially reduce inappropriate imaging.

PMID- 29198820
TI  - Resveratrol improves efficacy of oral amoxicillin against childhood fast
      breathing pneumonia in a randomized placebo-controlled double blind clinical
      trial.
AB  - Childhood pneumonia has been considered as a major cause of child morbidity and
      mortality worldwide. We aimed to investigate the effect of resveratral in
      synergizing with oral amoxicillin to improve the treatment outcome of oral
      amoxicillin administration against childhood fast breathing pneumonia. 647
      children diagnosed fast breathing pneumonia were recruited and randomized to
      receive oral amoxicillin plus either resveratrol (AX + RV) or placebo (AX +
      placebo). The primary outcome was defined as treatment failure up to day 3, while
      the secondary outcome was defined as treatment failure at day 6 and 12 upon
      follow up. Incidences of treatment failure up to day 3 was significantly lower in
      the AX + RV group than the AX + placebo group. From day 6-12, the incidences of
      treatment failure were increased in both treatment groups. However, treatment
      failure cases were still much lower in the AX + RV group on both revisits. No
      serious adverse reaction to treatment drugs were found in either of the two
      groups. Resveratrol improves efficacy of oral amoxicillin against childhood fast
      breathing pneumonia, supporting the clincial potential of reseveratrol as a
      potent adjuvent of oral amoxicillin in the treatment of childhood pneumonia with
      no adverse effects.

PMID- 29198821
TI  - In vitro antagonistic activity and the protective effect of probiotic Bacillus
      licheniformis Dahb1 in zebrafish challenged with GFP tagged Vibrio
      parahaemolyticus Dahv2.
AB  - In vitro antagonistic activity and the protective effect of probiotic Bacillus
      licheniformis Dahb1 in zebrafish (Danio rerio) challenged with GFP tagged Vibrio
      parahaemolyticus Dahv2 was studied. The cell free extract of probiotic B.
      licheniformis Dahb1 at 100 MUg mL-1 showed growth inhibition of V.
      parahaemolyticus Dahv2 in vitro. B. licheniformis Dahb1 also inhibited the
      biofilm growth of GFP tagged V. parahaemolyticus Dahv2 at 100 MUg mL-1 in vitro.
      The growth and survival of zebrafish was tested using probiotic B. licheniformis
      Dahb1. Weight (1.28 g) of zebrafish that received the cell free extract was much
      higher than in control (1.04 g). The mortality of zebrafish infected with GFP
      tagged V. parahaemolyticus Dahv2 at 107 Cfu mL-1 (Group IV) was 100%, whereas a
      complete survival of zebrafish that received the cell free extract of B.
      licheniformis Dahb1 at 107 Cfu mL-1 (Group VII) was observed after 30 days. The
      number of GFP tagged V. parahaemolyticus Dahv2 colonies in the intestine and
      gills significantly reduced after treatment with the cell free extract of B.
      licheniformis Dahb1. Furthermore, a significant decrease in the fluorescent
      colonies of GFP tagged V. parahaemolyticus Dahv2 was observed after treatment
      with the cell free extract of B. licheniformis Dahb1 under confocal laser
      scanning microscopy (CLSM). In conclusion, the cell free extract of B.
      licheniformis Dahb1 could prevent Vibrio infection by enhancing the growth and
      survival of zebrafish.

PMID- 29198822
TI  - Up-regulation of chemokine CXCL13 in systemic candidiasis.
AB  - Candida albicans is the leading cause of healthcare associated bloodstream
      infections. Chemokine CXCL13 is well-known involved in inflammation, but its role
      in candidemia has not been assessed. Our study firstly demonstrated that serum
      CXCL13 levels were significantly elevated in candidemic patients compared with
      bacteremic patients and control subjects by ELISA, and CXCL13 concentrations were
      positively and significantly correlated with clinical Sequential Organ Failure
      Assessment (SOFA) scores and several laboratory parameters in patients. Moreover,
      ROC curve analysis showed the diagnostic efficiency of CXCL13 was superior to CRP
      and PCT. To further study the role of CXCL13, a mouse model was established.
      Importantly, the data showed the dramatically elevated levels of CXCL13 in mice
      serum and infected kidney, were significantly correlated with renal fungal burden
      and pathology scores. In conclusion, our results indicated that CXCL13 had strong
      potential as a novel biomarker of diagnosis and prognosis for candidemia.

PMID- 29198823
TI  - microRNA-184 Induces a Commitment Switch to Epidermal Differentiation.
AB  - miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human.
      The importance of miR-184 was underscored by the discovery that point mutations
      in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related
      function in vivo remained unclear. Here, we report that the miR-184 knockout
      mouse model displayed increased p63 expression in line with epidermal
      hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced
      the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced
      clonogenicity and accelerated differentiation of human epidermal cells. We showed
      that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch
      activation and epidermal differentiation. The disease-causing miR-184C57U mutant
      failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss
      of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1,
      miR-184 regulates the transition from proliferation to early differentiation,
      while mis-expression or mutation in miR-184 results in impaired homeostasis.

PMID- 29198824
TI  - Inhibition of Farnesyltransferase Potentiates NOTCH-Targeted Therapy against
      Glioblastoma Stem Cells.
AB  - Accumulating evidence suggests that cancer cells with stem cell-like phenotypes
      drive disease progression and therapeutic resistance in glioblastoma (GBM). NOTCH
      regulates self-renewal and resistance to chemoradiotherapy in GBM stem cells.
      However, NOTCH-targeted gamma-secretase inhibitors (GSIs) exhibited limited
      efficacy in GBM patients. We found that farnesyltransferase inhibitors (FTIs)
      significantly improved sensitivity to GSIs. This combination showed significant
      antineoplastic and radiosensitizing activities in GBM stem cells, whereas non
      stem GBM cells were resistant. These combinatorial effects were mediated, at
      least partially, through inhibition of AKT and cell-cycle progression. Using
      subcutaneous and orthotopic GBM models, we showed that the combination of FTIs
      and GSIs, but not either agent alone, significantly reduced tumor growth. With
      concurrent radiation, this combination induced a durable response in a subset of
      orthotopic tumors. These findings collectively suggest that the combination of
      FTIs and GSIs is a promising therapeutic strategy for GBM through selectively
      targeting the cancer stem cell subpopulation.

PMID- 29198825
TI  - Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration
      Is Stimulated by Restorative Macrophages.
AB  - In skeletal muscle, new functions for vessels have recently emerged beyond oxygen
      and nutrient supply, through the interactions that vascular cells establish with
      muscle stem cells. Here, we demonstrate in human and mouse that endothelial cells
      (ECs) and myogenic progenitor cells (MPCs) interacted together to couple
      myogenesis and angiogenesis in vitro and in vivo during skeletal muscle
      regeneration. Kinetics of gene expression of ECs and MPCs sorted at different
      time points of regeneration identified three effectors secreted by both ECs and
      MPCs. Apelin, Oncostatin M, and Periostin were shown to control
      myogenesis/angiogenesis coupling in vitro and to be required for myogenesis and
      vessel formation during muscle regeneration in vivo. Furthermore, restorative
      macrophages, which have been previously shown to support myogenesis in vivo, were
      shown in a 3D triculture model to stimulate myogenesis/angiogenesis coupling,
      notably through Oncostatin M production. Our data demonstrate that restorative
      macrophages orchestrate muscle regeneration by controlling
      myogenesis/angiogenesis coupling.

PMID- 29198826
TI  - TRIM28 and Interacting KRAB-ZNFs Control Self-Renewal of Human Pluripotent Stem
      Cells through Epigenetic Repression of Pro-differentiation Genes.
AB  - Reprogramming to induced pluripotent stem cells (iPSCs) and differentiation of
      pluripotent stem cells (PSCs) are regulated by epigenetic machinery. Tripartite
      motif protein 28 (TRIM28), a universal mediator of Kruppel-associated box domain
      zinc fingers (KRAB-ZNFs), is known to regulate both processes; however, the exact
      mechanism and identity of participating KRAB-ZNF genes remain unknown. Here,
      using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation
      patterns in addition to H3K9me3 to cause stable gene repression during
      reprogramming. Using several expression datasets, we identified KRAB-ZNFs
      (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency.
      Moreover, we identified target genes repressed by these KRAB-ZNFs.
      Mechanistically, we demonstrated that these KRAB-ZNFs directly alter gene
      expression of important developmental genes by modulating H3K9me3 and DNA
      methylation of their promoters. In summary, TRIM28 employs KRAB-ZNFs to evoke
      epigenetic silencing of its target differentiation genes via H3K9me3 and DNA
      methylation.

PMID- 29198827
TI  - Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between
      Human Neurons and Astrocytes.
AB  - Human astrocytes network with neurons in dynamic ways that are still poorly
      defined. Our ability to model this relationship is hampered by the lack of
      relevant and convenient tools to recapitulate this complex interaction. To
      address this barrier, we have devised efficient coculture systems utilizing 3D
      organoid-like spheres, termed asteroids, containing pre-differentiated human
      pluripotent stem cell (hPSC)-derived astrocytes (hAstros) combined with neurons
      generated from hPSC-derived neural stem cells (hNeurons) or directly induced via
      Neurogenin 2 overexpression (iNeurons). Our systematic methods rapidly produce
      structurally complex hAstros and synapses in high-density coculture with iNeurons
      in precise numbers, allowing for improved studies of neural circuit function,
      disease modeling, and drug screening. We conclude that these bioengineered neural
      circuit model systems are reliable and scalable tools to accurately study aspects
      of human astrocyte-neuron functional properties while being easily accessible for
      cell-type-specific manipulations and observations.

PMID- 29198830
TI  - [Balance and gait problems related to frailty in physically active older women].

PMID- 29198828
TI  - Altered Differentiation Potential of Gaucher's Disease iPSC Neuronal Progenitors
      due to Wnt/beta-Catenin Downregulation.
AB  - Gaucher's disease (GD) is an autosomal recessive disorder caused by mutations in
      the GBA1 gene, which encodes acid beta-glucocerebrosidase (GCase). Severe GBA1
      mutations cause neuropathology that manifests soon after birth, suggesting that
      GCase deficiency interferes with neuronal development. We found that
      neuronopathic GD induced pluripotent stem cell (iPSC)-derived neuronal progenitor
      cells (NPCs) exhibit developmental defects due to downregulation of canonical
      Wnt/beta-catenin signaling and that GD iPSCs' ability to differentiate to
      dopaminergic (DA) neurons was strikingly reduced due to early loss of DA
      progenitors. Incubation of the mutant cells with the Wnt activator CHIR99021
      (CHIR) or with recombinant GCase restored Wnt/beta-catenin signaling and rescued
      DA differentiation. We also found that GD NPCs exhibit lysosomal dysfunction,
      which may be involved in Wnt downregulation by mutant GCase. We conclude that
      neuronopathic mutations in GCase lead to neurodevelopmental abnormalities due to
      a critical requirement of this enzyme for canonical Wnt/beta-catenin signaling at
      early stages of neurogenesis.

PMID- 29198829
TI  - Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using
      Interrupted Reprogramming.
AB  - A suitable source of progenitor cells is required to attenuate disease or affect
      cure. We present an "interrupted reprogramming" strategy to generate "induced
      progenitor-like (iPL) cells" using carefully timed expression of induced
      pluripotent stem cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc; OSKM)
      from non-proliferative Club cells. Interrupted reprogramming allowed controlled
      expansion yet preservation of lineage commitment. Under clonogenic conditions,
      iPL cells expanded and functioned as a bronchiolar progenitor-like population to
      generate mature Club cells, mucin-producing goblet cells, and cystic fibrosis
      transmembrane conductance regulator (CFTR)-expressing ciliated epithelium. In
      vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted
      reprogramming process could be metronomically applied to achieve controlled
      progenitor-like proliferation. By carefully controlling the duration of
      expression of OSKM, iPL cells do not become pluripotent, and they maintain their
      memory of origin and retain their ability to efficiently return to their original
      phenotype. A generic technique to produce highly specified populations may have
      significant implications for regenerative medicine.

PMID- 29198831
TI  - The Development of Left Ventricular Hypertrophy in Patients With Left-Sided
      Obstructive Lesions: Are Genetics at Play?

PMID- 29198832
TI  - Extracorporeal Membrane Oxygenation: An Expanding Role in Cardiovascular Care.

PMID- 29198834
TI  - Evaluation of Colorectal Cancer Screening in Federally Qualified Health Centers.
AB  - INTRODUCTION: Screening for colorectal cancer in average-risk adults is
      recommended beginning at age 50 years and continuing until age 75 years. This
      study was conducted to provide evidence for the effectiveness of an American
      Cancer Society grant program promoting colorectal cancer screening by
      implementing evidence-based interventions proven to increase screening rates.
      METHODS: Analysis compared colorectal cancer screening rates in 77 grant-funded
      federally qualified health centers between 2013 and 2015 to those of a sample of
      77 nonfunded federally qualified health centers selected using a genetic matching
      technique. The Uniform Data System from 2013 to 2015 provided data used in the
      analysis performed in 2016. RESULTS: Funded grantees differed significantly from
      nongrantees on several indicators at baseline. Genetic matching resulted in good
      quality matched samples. Both matched samples increased colorectal cancer
      screening rates over time. Grantees increased their colorectal cancer screening
      rates significantly more than nongrantees, especially between 2013 and 2014,
      where funded federally qualified health centers increased by 9% and nonfunded
      federally qualified health centers increased by 3%. Across the 3 years, increases
      were 12% and 9%, respectively. CONCLUSIONS: The findings suggest grant funding
      was effective in promoting improvements in colorectal cancer screening rates in
      funded federally qualified health centers, and these improvements exceed those of
      nonfunded federally qualified health centers. Funding that results in targeted,
      intensive efforts supported by technical assistance and accountability for data
      and reporting, can result in improved system policies and practices that, in
      turn, can increase screening rates among uninsured and underserved populations.

PMID- 29198833
TI  - Cardiovascular Risk After Kawasaki Disease - Findings From an Australian Case
      Control Study.

PMID- 29198835
TI  - Cinnamomum burmanini Blume increases bone turnover marker and induces tibia's
      granule formation in ovariectomized rats.
AB  - BACKGROUND: Bone fragility and an increase in susceptibility to fracture
      osteoporosis is characterized by a reduction in bone mass and the micro
      architectural deterioration of bone tissue. There is no previous study regarding
      the effect of Cinnamomum burmanini Blume on osteoporosis. OBJECTIVE: This study
      was aimed to investigate the effect of C. burmanini Blume on bone turnover
      marker, mineral elements, and mesostructure of ovariectomized rats. MATERIALS AND
      METHODS: Thirty female Wistar rats were randomly divided into five groups, which
      included a control group (sham surgery), ovariectomy group (OVX), and ovariectomy
      groups in the presence of ethanolic extract of C. burmanini Blume (EECB) at doses
      of 12.5; 25; 50 mg/kg body weight (BW). Analysis of serum C-telopeptide collagen
      type I (CTX) and osteocalcin (OC) were done by enzyme-linked immunosorbent assay
      (ELISA). Tibia mineral elements and mesostructure were analyzed by X-ray
      Fluorescence and Scanning Electron Microscopy, respectively. In silico study was
      performed by modeling protein structure using SWISS-MODEL server and Ramachandran
      plot analysis. RESULTS: The increase in OC and CTX were significantly attenuated
      by treatments of EECB. Ovariectomy significantly decreased Cu/Zn ratio compared
      to sham-operated rats (p < 0.05). Mesostructure of ovariectomized rats was
      significantly different compared with the control group. CONCLUSION: Cinnamon was
      able to normalize bone turnover markers, but, the mesostructure of hydroxyapatite
      crystal growth was achieved at the highest dose extract. In silico study showed
      that the active compound of EECB could not only support osteoclastogenesis
      process by decreasing the binding energy between RANKL and RANK, but also by
      inhibiting the interaction between OPG and RANK.

PMID- 29198837
TI  - Pareto-optimal reversed-phase chromatography separation of three insulin variants
      with a solubility constraint.
AB  - With the shift of focus of the regulatory bodies, from fixed process conditions
      towards flexible ones based on process understanding, model-based optimization is
      becoming an important tool for process development within the biopharmaceutical
      industry. In this paper, a multi-objective optimization study of separation of
      three insulin variants by reversed-phase chromatography (RPC) is presented. The
      decision variables were the load factor, the concentrations of ethanol and KCl in
      the eluent, and the cut points for the product pooling. In addition to the purity
      constraints, a solubility constraint on the total insulin concentration was
      applied. The insulin solubility is a function of the ethanol concentration in the
      mobile phase, and the main aim was to investigate the effect of this constraint
      on the maximal productivity. Multi-objective optimization was performed with and
      without the solubility constraint, and visualized as Pareto fronts, showing the
      optimal combinations of the two objectives productivity and yield for each case.
      Comparison of the constrained and unconstrained Pareto fronts showed that the
      former diverges when the constraint becomes active, because the increase in
      productivity with decreasing yield is almost halted. Consequently, we suggest the
      operating point at which the total outlet concentration of insulin reaches the
      solubility limit as the most suitable one. According to the results from the
      constrained optimizations, the maximal productivity on the C4 adsorbent (0.41
      kg/(m3 column h)) is less than half of that on the C18 adsorbent (0.87 kg/(m3
      column h)). This is partly caused by the higher selectivity between the insulin
      variants on the C18 adsorbent, but the main reason is the difference in how the
      solubility constraint affects the processes. Since the optimal ethanol
      concentration for elution on the C18 adsorbent is higher than for the C4 one, the
      insulin solubility is also higher, allowing a higher pool concentration. An
      alternative method of finding the suggested operating point was also evaluated,
      and it was shown to give very satisfactory results for well-mapped Pareto fronts.

PMID- 29198838
TI  - Another step in the journey: From CFTR mutation to sweat chloride concentration
      to survival.

PMID- 29198836
TI  - Facile synthesis of amine-functional reduced graphene oxides as modified quick,
      easy, cheap, effective, rugged and safe adsorbent for multi-pesticide residues
      analysis of tea.
AB  - Amine-functional reduced graphene oxide (amine-rGO) with different carbon chain
      length amino groups were successfully synthesized. The graphene oxides (GO)
      reduction as well as amino grafting were achieved simultaneously in one step via
      a facile solvothermal synthetic strategy. The obtained materials were
      characterized by X-ray diffraction, Raman spectroscopy, Fourier-transform
      infrared spectrometry and X-ray photoelectron spectroscopy to confirm the
      modification of GO with different amino groups. The adsorption performance of
      catechins and caffeine from tea acetonitrile extracts on different amine
      functional rGO samples were evaluated. It was found that tributylamine-functional
      rGO (tri-BuA-rGO) exhibited the highest adsorption ability for catechins and
      caffeine compared to GO and other amino group functional rGO samples. It was
      worth to note that the adsorption capacity of catechins on tri-BuA-rGO was 11
      times higher than that of GO (203.7mgg-1 vs 18.7mgg-1). Electrostatic
      interaction, pi-pi interaction and surface hydrophilic-hydrophobic properties of
      tri-BuA-rGO played important roles in the adsorption of catechins as well as
      caffeine. The gravimetric analysis confirmed that the tri-BuA-rGO achieved the
      highest efficient cleanup preformance compared with traditional dispersive solid
      phase extraction (dSPE) adsorbents like primary-secondary amine (PSA),
      graphitized carbon black (GCB) or C18. A multi-pesticides analysis method based
      on tri-BuA-rGO is validated on 33 representative pesticides in tea using gas
      chromatography coupled to tandem mass spectrometry or high-performance liquid
      chromatography coupled with tandem mass spectrometry. The analysis method gave a
      high coefficient of determination (r2>0.99) for each pesticide and satisfactory
      recoveries in a range of 72.1-120.5%. Our study demonstrated that amine
      functional rGO as a new type of QuEChERS adsorbent is expected to be widely
      applied for analysis of pesticides at trace levels.

PMID- 29198839
TI  - Notch-mediated Sox9+ cell activation contributes to kidney repair after partial
      nephrectomy.
AB  - AIMS: Partial nephrectomy is a surgical technique as an alternative for
      traditional radical nephrectomy. The advantage of partial nephrectomy technique
      is nephron-sparing, however, whether the remaining kidney tissue could regenerate
      the lost nephron is still unknown. The current work is to investigate the kidney
      tissue repair process and the related cellular and molecular mechanism. MAIN
      METHODS: We used a novel unilateral partial nephrectomy mouse model to study
      kidney repair, and focused on a population of Sox9+ progenitor cells to study
      their pivotal role in the regenerative process. Kidney function after nephrectomy
      was measured using creatinine and urea nitrogen assay kit. Wound healing was
      assessed by Masson Trichrome Staining. Tissue regeneration was tested by Sox9+
      cells immunofluorescence staining. The differentiation potential of Sox9+ cells
      were assessed by immunoanalysis with various tubular cell markers. Notch
      activation was determined by qPCR and Western blotting. KEY FINDINGS: After
      partial nephrectomy, we found that massive Sox9+ cells emerged one day after the
      surgery and lasted for up to 20days. The Sox9+ cells had proliferative capacity
      and could give rise to epithelial cells of proximal tubule, Henle's loop, distal
      tubule, collecting duct, and the parietal layer of glomerulus. We also found that
      the activation of Sox9+ cells was mediated by Notch signaling pathway.
      SIGNIFICANCE: The current study reveals that Notch-mediated Sox9+ cell activation
      can contribute to kidney tubule regeneration after unilateral partial nephrectomy
      in mice.

PMID- 29198840
TI  - Isolation of saprophytic Leptospira spp. from a selected environmental water
      source of Argentina.
AB  - Ten Leptospira spp. strains were isolated from water samples from Nievas stream,
      Olavarria, Buenos Aires province (Argentina). The isolates showed the typical
      motility and morphology of the genus Leptospira under dark field microscopy,
      developing in liquid EMJH medium after eight days of incubation at 13 degrees C
      and 30 degrees C. All isolates were negative by the Multiple Locus Variable
      Number Tandem Repeat Analysis (MLVA). Molecular identification by 16S rRNA gene
      sequencing identified all isolates as nonpathogenic leptospires. Four isolates
      showed a genetic profile identical to that of the reference strain Leptospira
      biflexa serovar Patoc, and six isolates revealed sequence similarities within the
      97-98% range, closely related to Leptospira yanagawae and Leptospira meyeri,
      respectively. Strains ScialfaASA42, ScialfaASA45, ScialfaASA44, ScialfaASA47,
      ScialfaASA49, ScialfaASA50 and ScialfaASA51 possibly represent a novel species of
      the genus Leptospira.

PMID- 29198841
TI  - [Antimicrobial susceptibility in isolates of Streptococcus equi subsp. equi from
      Buenos Aires province, Argentina].
AB  - Streptococcus equi subsp. equi is the etiologic agent of strangles, an infectious
      disease affecting the upper respiratory tract and head and neck lymph nodes of
      equines. Routine antimicrobial therapy includes penicillin (PEN) as antibiotic of
      first choice. Streptococci are usually susceptible to PEN and only a few
      antimicrobial studies had been performed. The aim of this work was to study the
      antimicrobial susceptibility profile of S. equi from Buenos Aires, Argentina.
      Ninety-two isolates were studied by the single disk method to PEN, cefotaxime,
      erythromycin (ERY), tetracycline, enrofloxacin (ENR), trimethoprim
      sulfamethoxazole (TMS), ciprofloxacin, clindamycin (CLI), streptomycin (STR) and
      florfenicol. Minimum inhibitory concentration (MIC) to PEN and antibiotics with
      resistance and intermediate susceptibility were tested. High percentages of
      susceptibility were obtained by the disk diffusion method and MIC values of PEN,
      TMS and CLI were found to be under the breakpoint values. Resistant strains of
      ENR and STR with MIC50, MIC90 and MIC ranges above breakpoints were identified.
      These findings confirm that PEN may be used empirically because resistant strains
      were not found in Buenos Aires. Emphasis is placed on the rational use of
      antibiotics to achieve therapeutic success, to prevent chronicity, recurrence of
      infections and the emergence of resistance.

PMID- 29198842
TI  - Prevalence of and Differences in Salad Bar Implementation in Rural Versus Urban
      Arizona Schools.
AB  - BACKGROUND: Rural children consume more calories per day on average than urban
      children, and they are less likely to consume fruit. Self-service salad bars have
      been proposed as an effective approach to better meet the National School Lunch
      Program's fruit and vegetable recommendations. No studies have examined how rural
      and urban schools differ in the implementation of school salad bars. OBJECTIVE:
      To compare the prevalence of school-lunch salad bars and differences in
      implementation between urban and rural Arizona schools. DESIGN: Secondary
      analysis of a cross-sectional web-based survey. PARTICIPANTS/SETTING: School
      nutrition managers (N=596) in the state of Arizona. MAIN OUTCOMES MEASURED:
      National Center for Education Statistics locale codes defined rural and urban
      classifications. Barriers to salad bar implementation were examined among schools
      that have never had, once had, and currently have a school salad bar. Promotional
      practices were examined among schools that once had and currently have a school
      salad bar. STATISTICAL ANALYSES PERFORMED: Generalized estimating equation models
      were used to compare urban and rural differences in presence and implementation
      of salad bars, adjusting for school-level demographics and the clustering of
      schools within districts. RESULTS: After adjustment, the prevalence of salad bars
      did not differ between urban and rural schools (46.9%+/-4.3% vs 46.8%+/-8.5%,
      respectively). Rural schools without salad bars more often reported perceived
      food waste and cost of produce as barriers to implementing salad bars, and
      funding was a necessary resource for offering a salad bar in the future, as
      compared with urban schools (P<0.05). No other geographic differences were
      observed in reported salad bar promotion, challenges, or resources among schools
      that currently have or once had a salad bar. CONCLUSIONS: After adjustment, salad
      bar prevalence, implementation practices, and concerns are similar across
      geographic settings. Future research is needed to investigate methods to address
      cost and food waste concerns in rural areas.

PMID- 29198843
TI  - How Do I Know Whether It Is an Ethical Issue? Helping Registered Dietitian
      Nutritionists Identify Ethical Issues in Practice.

PMID- 29198844
TI  - Attitude and Behavior Factors Associated with Front-of-Package Label Use with
      Label Users Making Accurate Product Nutrition Assessments.
AB  - BACKGROUND: Front-of-package (FOP) labels are increasing in popularity on retail
      products. Reductive FOP labels provide nutrient-specific information, whereas
      evaluative FOP labels summarize nutrient information through icons. Better
      understanding of consumer behavior regarding FOP labels is beneficial to
      increasing consumer use of nutrition labeling when making grocery purchasing
      decisions. OBJECTIVE: We aimed to determine FOP label format effectiveness in
      aiding consumers at assessing nutrient density of food products. In addition, we
      sought to determine relationships between FOP label use and attitude toward
      healthy eating, diet self-assessment, self-reported health and nutrition
      knowledge, and label and shopping behaviors. DESIGN: A between-subjects
      experimental design was employed. Participants were randomly assigned to one of
      four label conditions: Facts Up Front, Facts Up Front Extended, a binary symbol,
      and no-label control. PARTICIPANTS/SETTING: One hundred sixty-one US primary
      grocery shoppers, aged 18 to 69 years. Participants were randomly invited to the
      online study. INTERVENTION: Participants in one of four label condition groups
      viewed three product categories (cereal, dairy, and snacks) with corresponding
      questions. MAIN OUTCOME MEASURES: Adults' nutrition assessment of food products
      based on different FOP label formats, along with label use and attitude toward
      healthy eating, diet self-assessment, self-reported health and nutrition
      knowledge, and label and shopping behaviors. STATISTICAL ANALYSES PERFORMED: Data
      analyses included descriptive statistics, chi2 tests, and logistical regression.
      Significant outcomes were set to alpha=.05. RESULTS: Participants selected the
      more nutrient-dense product in the snack food category when it contained an FOP
      label. Subjective health and nutrition knowledge and frequency of selecting food
      for healthful reasons were associated with FOP label use (P<0.01 and P<0.05,
      respectively). CONCLUSIONS: Both Facts Up Front (reductive) and binary
      (evaluative) FOP labels appear effective for nutrition assessment of snack
      products compared with no label. Specific attitude and behavior factors were
      associated with label use.

PMID- 29198845
TI  - Gardening Experience Is Associated with Increased Fruit and Vegetable Intake
      among First-Year College Students: A Cross-Sectional Examination.
AB  - BACKGROUND: Gardening interventions have been shown to increase fruit and
      vegetable (F/V) intake among school-aged children. It is unknown whether these
      effects persist into later adolescence or adulthood, and little is known about
      whether gardening in later adolescence is related to F/V intake. OBJECTIVE: To
      identify the relationship between both childhood and recent (within the past 12
      months) gardening experiences and current F/V intake among college students.
      DESIGN/PARTICIPANTS: A cross-sectional evaluation of 1,121 college freshmen with
      suboptimal F/V consumption from eight US universities. MAIN OUTCOME MEASURES:
      Participants completed the National Cancer Institute Fruit and Vegetable Screener
      and questions about gardening experiences. Respondents were grouped as having
      gardened or not gardened during childhood and recently. STATISTICAL ANALYSES
      PERFORMED: A linear mixed model was used to evaluate the relationship between
      childhood and recent gardening and current F/V intake. RESULTS: Of the student
      participants, 11% reported gardening only during childhood, 19% reported
      gardening only recently, 20% reported gardening both as a child and recently, and
      49% of students reported never having gardened. Students who gardened both during
      childhood and recently had a significantly higher mean current intake of F/V
      compared with students who never gardened (2.5+/-0.6 vs 1.9+/-0.5 cup equivalents
      [CE], respectively; P<0.001). In addition, F/V intake increased with frequency of
      recent gardening engagement when comparing students who did not garden with those
      who gardened monthly or weekly (2.1+/-0.5 CE, 2.4+/-0.6 CE, and 2.8+/-0.7 CE,
      respectively; P<0.001). CONCLUSIONS: This analysis suggests that the combination
      of childhood and recent gardening experience is associated with greater current
      F/V intake among first-year college students not currently meeting national F/V
      recommendations. In addition, a greater frequency of gardening experience may
      further enhance this effect.

PMID- 29198846
TI  - Utilization of the Bologna criteria: a promise unfulfilled? A review of published
      and unpublished/ongoing trials.
AB  - OBJECTIVE: To study the use of the Bologna criteria (BC) for the definition of
      poor ovarian responders (POR) in clinical practice and research. DESIGN:
      Systematic review of published and unpublished/ongoing trials between January
      2012 and August 2017 on POR. SETTING: Not applicable. PATIENT(S): Not applicable.
      INTERVENTION(S): The databases were searched using the relevant medical subject
      headings including all subheadings. The search was limited to humans and English
      language. The references of the included studies were cross-searched for possibly
      missed articles. Only clinical trials providing an evidence level >= III were
      included. Case reports, review, letters, and hypothetical articles were excluded.
      MAIN OUTCOME MEASURE(S): Extracted studies were divided into two groups: studies
      in which the BC were used or not. RESULT(S): One hundred nine published clinical
      studies analyzing a total of 30,540 women and 112 unpublished/ongoing trials were
      identified. The BC were used to define POR in 56 (51%) of the published and 44
      (39%) of the unpublished trials. The use of the BC gradually increased from 29%
      to 53% from 2012 to 2017. Asian researchers were more likely to use the BC
      compared with European and North American researchers (65%, 49%, and 23%,
      respectively). Neither the design of the study nor the impact factor of the
      publishing journal was correlated with the use of the BC. CONCLUSION(S): There is
      still reluctance to use the BC for the definition of POR, which makes it
      difficult to combine data from small studies and reach a meaningful conclusion.

PMID- 29198847
TI  - First delivery in a leukemia survivor after transplantation of cryopreserved
      ovarian tissue, evaluated for leukemia cells contamination.
AB  - OBJECTIVE: To describe a successful autologous ovarian tissue re-transplantation
      in a sterile leukemia survivor after evaluation for minimal residual disease and
      provide a review of the current literature. DESIGN: Presentation of a carefully
      designed workup taken to evaluate tissue for minimal residual disease, its
      limitations, and applicability to other patients. To date, there have not been
      any publications of auto-transplantations in leukemia survivors, owing to an
      estimated high risk for malignancy induction. SETTING: Large tertiary hospital.
      PATIENT(S): A 19-year-old acute myeloid leukemia patient underwent ovarian tissue
      cryopreservation during complete remission before bone marrow transplantation.
      After prolonged amenorrhea, the patient desired pregnancy. Laboratory tests
      showed antimullerian hormone <0.1 ng/mL and FSH 116 mIU/mL. Ultrasound revealed
      no ovarian follicles. INTERVENTION(S): Ovarian tissue cryopreservation and auto
      transplantation. Histology, immunohistochemistry, FISH, next-generation
      sequencing, and xenotransplantation were done to evaluate thawed tissue samples
      for the presence of leukemia cells. MAIN OUTCOME MEASURE(S): Evidence for
      leukemia cells in thawed ovarian tissue, reproductive outcomes and live birth
      after transplantation, and leukemia-free survival. RESULT(S): Histology was
      negative for leukemia cells. Three severe combined immunodeficiency mice, grafted
      with tissue fragments, were followed for 6 months and showed no
      macroscopic/microscopic signs for leukemia. Fluorescence in situ hybridization
      for disease-specific gene rearrangement resulted in a read below the probe's cut
      off. A next-generation sequencing panel of genes implicated in myeloproliferative
      disorders did not reveal any significant molecular event. Transplantation was
      performed, followed by ovarian stimulation and IVF, resulting in the delivery of
      healthy newborn. More than 2 years have elapsed since transplantation, and the
      patient is leukemia free. CONCLUSION(S): Harvesting during complete remission,
      combined with intense tissue evaluation before transplantation, allowed a safe,
      successful transplantation in an acute myeloid leukemia survivor.

PMID- 29198848
TI  - Association between surgically diagnosed endometriosis and adverse pregnancy
      outcomes.
AB  - OBJECTIVE: To examine the association between surgically diagnosed endometriosis
      and pregnancy outcomes in subsequent pregnancies. DESIGN: Retrospective cohort
      study of women who delivered a singleton live birth from 2003 to 2013 in Ottawa,
      Ontario, Canada. SETTING: Tertiary level academic center. PATIENT(S): Pregnant
      women with surgically diagnosed endometriosis were identified using International
      Classification of Diseases-10 codes from previous hospital admissions and were
      compared with pregnant women with no prior admission for endometriosis for the
      occurrences of adverse pregnancy outcomes. INTERVENTION(S): Observational study.
      MAIN OUTCOME MEASURE(S): Gestational hypertension, preeclampsia, placenta previa,
      placental abruption, postpartum hemorrhage, preterm birth, low birth weight,
      small for gestational age, and neonatal intensive care unit admission. RESULTS:
      Among the 52,202 eligible mother-infant pairs, we identified 469 mothers with
      surgically diagnosed endometriosis from a previous hospital encounter. Compared
      with women without endometriosis, women with endometriosis were on average older
      and were more likely to be primiparous, have lower gravidity, have a history
      spontaneous abortion, conceive with assisted reproductive technology, and reside
      in areas with higher neighborhood income and lower proportion of immigrants.
      Women with endometriosis were found to have an elevated risk of placenta previa
      (relative risk [RR], 3.30; 95% confidence interval [CI], 1.65-5.40) and cesarean
      delivery (RR, 1.24; 95% CI, 1.10-1.40). After adjustment for potential
      confounding factors, women with endometriosis were found to have a significantly
      elevated risk of placenta previa compared with women without endometriosis
      (adjusted RR, 2.54; 95% CI, 1.39-4.64). CONCLUSION(S): This study identifies
      baseline demographic differences between women with and without endometriosis and
      suggests that women affected by endometriosis have an independently elevated risk
      of placenta previa in pregnancy.

PMID- 29198849
TI  - Oxalate-Degrading Enzyme Recombined Lactic Acid Bacteria Strains Reduce
      Hyperoxaluria.
AB  - OBJECTIVE: To develop recombinant lactic acid bacteria (LAB) strains that express
      oxalate-degrading enzymes through biotechnology-based approach for the treatment
      of hyperoxaluria by oral administration. MATERIAL AND METHODS: The coding gene of
      oxalate decarboxylase (ODC) and oxalate oxidase (OxO) was transformed into
      Lactococcus lactis MG1363. The oxalate degradation ability in vitro was evaluated
      in media with high concentration of oxalate. Hyperoxaluria rat models through
      high oxalate diet were given recombinant LAB through oral administration. Twenty
      four-hour urinary oxalate was measured, and kidney stone formation was
      investigated. RESULTS: LAB recombined with the coding gene of ODC could
      effectively decrease the amount of oxalate in the media and in the urine of rats.
      Moreover, the formation of calcium oxalate crystals in kidneys was also
      inhibited. The acid-induced promoter p170 significantly enhanced the reduction of
      hyperoxaluria. However, recombinant LAB expressing heterologous OxO showed less
      efficiency in oxalate degradation even in the presence of p170. CONCLUSION: LAB
      expressing ODC is more efficient in degradation of oxalate in vitro and in vivo
      than that expressing OxO. This present study provided novel recombinant probiotic
      strains as a potential treatment tool against oxalosis.

PMID- 29198851
TI  - Real-time observations of tooth demineralization in 3 dimensions using X-ray
      microtomography.
AB  - OBJECTIVES: The immediate aim of this study was to develop and test a method to
      record, visualize and quantify real-time demineralization (or remineralization)
      of teeth in vitro using X-ray microtomography (XMT or micro-CT). The longer term
      objective is to improve understanding of demineralization processes, allowing the
      creation of better artificial models of dental caries and better quantification
      of the efficacy of caries treatment and prevention regimes. METHODS: For
      demineralization studies, the tooth is mounted in a plastic container through
      which the demineralizing solution is circulated during simultaneous repeated
      scanning. Key features of the method are safe circulation of the demineralizing
      solution, periodic interruption to adjust X-ray filament current and re-focus,
      accurate beam-hardening correction and calibration, alignment of reconstructed
      scans, and normalization of grey-levels to compensate for changes in the X-ray
      spectrum. The method was tested by scanning an extracted third molar during 8days
      of demineralization. RESULTS: From the reconstructed 3D images, the progression
      of an artificial carious lesion could be visualized and quantified. The lesion
      progressed at approximately 0.1mm per day and appeared to be more erosive in
      nature. CONCLUSIONS: A successful method has been developed to monitor real-time
      demineralization in 3 dimensions. Further work is now needed to create better
      models of true carious lesions. CLINICAL SIGNIFICANCE: Observation of the
      dynamics of demineralization and remineralization will aid in the development of
      therapies to treat and prevent dental caries.

PMID- 29198850
TI  - Safety and Efficacy of En Bloc Transurethral Resection With 1.9 um Vela Laser for
      Treatment of Non-Muscle-invasive Bladder Cancer.
AB  - OBJECTIVES: To evaluate the safety and efficacy of 1.9 um Vela laser in treatment
      of primary non-muscle-invasive bladder cancer. METHODS: The data of the patients
      with non-muscle-invasive bladder cancer treated by either en bloc transurethral
      resection with 1.9 um Vela laser (n = 26) or conventional transurethral resection
      of bladder tumor (n = 44) were analyzed retrospectively. The preoperative
      characteristics and intraoperative complications were compared in the 2 groups.
      RESULTS: Patients who were treated by 1.9 um Vela laser obtained a higher rate of
      specimens meeting the requirements of pathologic assessment for tumor staging
      compared with the patients treated by conventional transurethral resection of
      bladder tumor. No obturator nerve reflex and bladder perforation occurred during
      surgery in the 1.9 um Vela laser group. However, 7 patients in the conventional
      transurethral resection of bladder tumor group encountered obturator nerve
      reflex, and 3 of them encountered bladder perforation (P <.05). There were no
      significant differences between the 2 groups in operative duration and
      transfusion rate. Patients in the 1.9 um Vela laser group had shorter
      postoperative continuous bladder irrigation time than that in the conventional
      transurethral resection of bladder tumor group. There was no significant
      difference in the overall recurrence rate between the 2 groups during the follow
      up periods. CONCLUSION: En bloc transurethral resection with 1.9 um Vela laser in
      the treatment of non-muscle-invasive bladder cancer demonstrates an advantage
      over conventional transurethral resection of bladder tumor in reducing
      intraoperative complications, improving the quality of the specimens admitted for
      pathologic assessment, and shortening the duration of postoperative continuous
      bladder irrigation.

PMID- 29198852
TI  - Demographic factors and attitudes that influence the support of the general
      public for the introduction of universal healthcare in Ireland: A national
      survey.
AB  - Ireland is still struggling to end the inequitable two-tiered health system and
      introduce universal healthcare (UHC). Public opinion can influence health policy
      choice and implementation. However, the public are rarely asked for their views.
      This study describes the demographic and attitudinal factors that influence the
      support of the public for the introduction of UHC. It provides data on a
      nationally representative survey sample of n=972. There are high levels of
      support for the introduction of UHC (n=846 87.0%). Logistic regression analyses
      indicated that demographic factors, such as, the location of respondent, whether
      the respondent was in receipt of Government supported healthcare, a purchaser of
      private health insurance or neither; plus attitudinal factors, such as, opinions
      on the Government prioritising healthcare, healthcare being free at the point of
      access, taxes being increased to provide care free at the point of access and how
      well informed participants felt about UHC were associated with agreeing with the
      introduction of UHC in Ireland. This paper is timely for policy leaders both in
      Ireland and internationally as countries with UHC, such as the United Kingdom,
      are facing difficulties maintaining health services in the public realm.

PMID- 29198853
TI  - Effects of exercise on cancer patients suffering chemotherapy-induced peripheral
      neuropathy undergoing treatment: A systematic review.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common
      neurological and clinically relevant side effect of many commonly used
      chemotherapeutic agents. Moreover, little effort has been done to investigate the
      potentially beneficial effects of specific exercises to counteract the CIPN
      symptoms. OBJECTIVE: This document aims to summarize and analyze systematically
      the current body of evidence about the effects of specific exercise protocols on
      CIPN symptoms, balance control, physical function and quality of life in patients
      with CIPN. LITERATURE SURVEY: Specific terms were identified for the literature
      research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science. METHODOLOGY:
      Five manuscripts were considered eligible for this review. Quality appraisal
      distinguished two studies as high quality investigations while three with low
      quality. Results were summarized in the following domains: "CIPN symptoms",
      "Static balance control", "Dynamic balance control", "Quality of life and
      Physical function". SYNTHESIS: Significant improvements were detected on postural
      control. Additionally, patients' quality of life and independence were found
      ameliorated after exercise sessions. Combined exercise protocols including
      endurance, strength and sensorimotor training showed larger improvements.
      CONCLUSIONS: This systematic review comes from a highly selected but small source
      of data. Nevertheless, specific exercise for cancer patients undergoing
      chemotherapy with CIPN symptoms should be recommended since these interventions
      appeared as feasible and have been demonstrated as useful tools to counteract
      some of the limitations due to chemotherapy.

PMID- 29198854
TI  - Efficacy and safety of transversus abdominis plane blocks versus thoracic
      epidural anesthesia in patients undergoing major abdominal oncologic resections:
      A prospective, randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to compare patient outcomes for
      thoracic epidural anesthesia (TEA) with transversus abdominis plane (TAP) blocks.
      METHODS: A prospective, randomized trial was performed for patients undergoing
      abdominal oncologic surgeries. RESULTS: There were 32 TAP and 35 TEA subjects.
      The TEA group demonstrated increased episodes of hypotension in the first 24 h (3
      v 0.6, p = 0.02). There was no difference in 24-48 h fluid balance between the
      groups. Overall parenteral morphine equivalents of opioids administered for the
      TEA group were higher for each postoperative day (p < 0.05). The post-operative
      survey did not demonstrate any difference in subjective pain between the TAP and
      TEA groups (6 v 6 p = 0.35). There was no attributable morbidity associated with
      either technique. CONCLUSIONS: TAP block use was associated with lower parenteral
      morphine equivalent usage and decreased incidence of hypotension in the early
      post-operative period compared to TEA.

PMID- 29198855
TI  - Is verification of peer review service necessary to support scientific growth?

PMID- 29198856
TI  - Naringenin glucuronidation in liver and intestine microsomes of humans, monkeys,
      rats, and mice.
AB  - Naringenin, a flavanone found in citrus fruits, is mainly metabolized into
      glucuronide(s) by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the
      present study, the glucuronidation of naringenin in the liver and intestine
      microsomes of humans, monkeys, rats, and mice was examined. The kinetics of 7
      glucuronidation in human liver and intestine microsomes followed the Michaelis
      Menten model. Kinetics in mouse liver and intestine microsomes also followed the
      Michaelis-Menten model, whereas those in monkey and rat liver microsomes fit the
      biphasic model. Kinetics in monkey and rat intestine microsomes fit the Michaelis
      Menten and substrate inhibition models, respectively. CLint values were mice >
      monkeys > rats > humans for liver microsomes, and mice > rats > monkeys > humans
      for intestine microsomes. In 4'-glucuronidation, activities in human liver
      microsomes and monkey liver and intestine microsomes were negligible or very low.
      Kinetics in rat and mouse liver microsomes followed the biphasic and Michaelis
      Menten models, respectively. CLint values were rats > mice for liver microsomes,
      and rats > mice > humans for intestine microsomes. These results suggest that the
      metabolic abilities and regioselectivity of UGT enzymes toward naringenin in the
      liver and intestines generally differ between primates and rodents.

PMID- 29198857
TI  - Probabilistic exposure assessment to face and oral care cosmetic products by the
      French population.
AB  - Cosmetic exposure data for face and mouth are limited in Europe. The aim of the
      study was to assess the exposure to face cosmetics using recent French
      consumption data (Ficheux et al., 2016b, 2015). Exposure was assessed using a
      probabilistic method for thirty one face products from four lines of products:
      cleanser, care, make-up and make-up remover products and two oral care products.
      Probabilistic exposure was assessed for different subpopulation according to sex
      and age in adults and children. Pregnant women were also studied. The levels of
      exposure to moisturizing cream, lip balm, mascara, eyeliner, cream foundation,
      toothpaste and mouthwash were higher than the values currently used by the
      Scientific Committee on Consumer Safety (SCCS). Exposure values found for eye
      shadow, lipstick, lotion and milk (make-up remover) were lower than SCCS values.
      These new French exposure values will be useful for safety assessors and for
      safety agencies in order to protect the general population and the at risk
      populations.

PMID- 29198858
TI  - Phenolic components and assessment of biological properties of Tchihatchewia
      isatidea Boiss. extracts: Docking and functional approaches for designing novel
      products.
AB  - The potentiality of bioactive phenolic compounds may result in plant extracts
      having multiple biological activities. The aim of this study was to investigate
      into the biological activities of the methanolic, ethyl acetate, and water
      extracts of Tchihatchewia isatidea Boiss, an endemic medicinal plant of Turkey.
      The phenolic compositions of the extracts were confirmed using RP-HPLC. Extracts
      were screened for their potential antioxidant through a panoply of assays; their
      anti-diabetic potential, and plausible inhibitory activity against tyrosinase and
      acetylcholinesterase. Molecular modelling methods were also used to assess the
      docking properties of phenolic compounds on tyrosinase. The major and most
      abundant compounds were rosmarinic acid (570 +/- 14 MUg/g extract in the
      methanolic extract), ferrulic acid (336 +/- 6 MUg/g extract in the methanolic
      extract), (+)-catechin (340 +/- 4 MUg/g extract in the water extract), apigenin
      (182 +/- 4 MUg/g extract in the methanolic extract), and epicatechin (188 +/- 12
      MUg/g extract in the water extract). Radical scavenging, reducing capacity, and
      metal chelating activities were detected in the extracts, with preponderance
      activity observed in the methanolic extract. In conclusion, the potential
      clinical applications observed during this study may provide new insights into
      the molecular aspect particularly for neuroprotective and anti-diabetic
      mechanisms involving oxidative stress.

PMID- 29198859
TI  - Selecting among three basic fitness landscape models: Additive, multiplicative
      and stickbreaking.
AB  - Fitness landscapes map genotypes to organismal fitness. Their topographies depend
      on how mutational effects interact - epistasis - andare important for
      understanding evolutionary processes such as speciation, the rate of adaptation,
      the advantage of recombination, and the predictability versus stochasticity of
      evolution. The growing amount of data has made it possible to better test
      landscape models empirically. We argue that this endeavor will benefit from the
      development and use of meaningful basic models against which to compare more
      complex models. Here we develop statistical and computational methods for fitting
      fitness data from mutation combinatorial networks to three simple models:
      additive, multiplicative and stickbreaking. We employ a Bayesian framework for
      doing model selection. Using simulations, we demonstrate that our methods work
      and we explore their statistical performance: bias, error, and the power to
      discriminate among models. We then illustrate our approach and its flexibility by
      analyzing several previously published datasets. An R-package that implements our
      methods is available in the CRAN repository under the name Stickbreaker.

PMID- 29198861
TI  - Compliance to care guidelines for Duchenne muscular dystrophy in Italy.

PMID- 29198860
TI  - Comparative of transcranial magnetic stimulation and other treatments in
      experimental autoimmune encephalomyelitis.
AB  - The effects of transcranial magnetic stimulation (TMS), natalizumab (nata),
      dimethyl fumarate (DMF) and dexamethasone (DEX) on clinical score and oxidative
      stress produced by a single dose of myelin oligodendrocyte glycoprotein (MOG) in
      tail of Dark Agouti rats was studied. TMS (60Hz and 0.7 mT), nata (5mg/kg), DMF
      (15mg/kg) and DEX (300MUg/kg) was applied for 21 after the administration of MOG
      (150MUg). We estimated clinical score, as well as lipid peroxides, carbonylated
      proteins and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio content
      in brain, spinal cord and blood. MOG triggered significant increase in clinical
      score and in the levels of lipid peroxides and carbonylated proteins levels, but
      reduced GSH/GSSG ratio in brain, spinal cord and blood. Both TMS and clinical
      treatments, although TMS more significantly, decreased the changes caused by MOG
      administration. These results support the antioxidant and neuroprotective action
      of TMS, as well as an activity higher than other clinical treatments.

PMID- 29198862
TI  - Towards smart biocide-free anti-biofilm strategies: Click-based synthesis of
      cinnamide analogues as anti-biofilm compounds against marine bacteria.
AB  - A set of triazole-based analogues of N-coumaroyltyramine was designed to discover
      potential leads that may help in the control of bacterial biofilms. the most
      potent compounds act as inhibitors of biofilm development with EC50 closed to
      ampicillin (EC50 = 11 MUM) without toxic effect on bacterial growth even at high
      concentrations(100 MUM).

PMID- 29198863
TI  - Synthesis, antitumor activity, and cytotoxicity of 4-substituted 1-benzyl-5
      diphenylstibano-1H-1,2,3-triazoles.
AB  - Trisubstituted 5-organostibano-1H-1,2,3-triazoles (3a-f) were synthesized by the
      Cu-catalyzed azide-alkyne cycloaddition of various ethynylstibanes (1) with
      benzylazide (2) in the presence of CuBr (5 mol%) under aerobic conditions. The
      reaction of 5-stibanotriazoles with HCl afforded C5-unsubstituted 1,2,3-triazoles
      (4a-f). The antitumor activity of trisubstituted 5-organostibano-1H-1,2,3
      triazoles (3a-f) and their 5-unsubstituted 1,2,3-triazoles (4a-f) were evaluated
      in several tumor cell lines. All 5-stibanotriazoles (3a-f) exerted an excellent
      antitumor activity. On the contrary, 5-unsubstituted 1,2,3-triazoles (4a-f)
      without a diphenylantimony group in the molecule exhibited very low antitumor
      activity compared with 5-stibanotriazoles (3a-f). In compounds of both the
      series, the substituted 4-butyl group appeared to decrease antitumor activity.
      However, results suggested that organometal (antimony) in the molecule was
      required for greater antitumor activity. In addition, all 5-stibanotriazoles (3a
      f), but not all 5-unsubstituted 1,2,3-triazoles (4a-f), exhibited cytotoxicity in
      normal vascular endothelial cells derived from bovine aorta. Among the compounds
      (3b-e) that exhibited excellent antitumor activity, those with 4-methylphenyl
      (3b) and 1-cyclohexenyl (3e) showed relatively low cytotoxicity to vascular
      endothelial cells. Together, these results suggest that trisubstituted 5
      organostibano-1H-1,2,3-triazoles, including compounds 3b and 3e, may serve as
      potential anticancer therapeutic drugs in the future.

PMID- 29198864
TI  - Small molecule inhibitors of anthrax edema factor.
AB  - Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus
      anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease
      in humans exposed to B. anthracis. ET is a bipartite toxin composed of two
      proteins secreted by the vegetative bacteria, edema factor (EF) and protective
      antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax
      edema factor is the subject of this letter. First we demonstrate that the small
      molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly
      with EF and blocks enzymatic activity. We then show that the adenosine portion of
      FSBA can be replaced to provide more drug-like molecules which are up to 1000
      fold more potent against EF relative to FSBA, display low cross reactivity when
      tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell
      based assay of cAMP production.

PMID- 29198865
TI  - Histone H3 peptides incorporating modified lysine residues as lysine-specific
      demethylase 1 inhibitors.
AB  - Lysine-specific demethylase 1 (LSD1) is a flavin-dependent enzyme that removes
      methyl groups from mono- or dimethylated lysine residues at the fourth position
      of histone H3. We have previously reported several histone H3 peptides containing
      an LSD1 inactivator motif at Lys-4. In this study, histone H3 peptides having a
      trans-2-phenylcyclopropylamine (PCPA), a 2,5-dihydro-1H-pyrrole, and a 1,2,3,6
      tetrahydropyridine moiety at Lys-4 were prepared along with related compounds
      possessing a shorter side chain at the fourth position. Enzymatic assays showed
      that PCPA peptides containing a longer side chain, which can react with FAD in
      the active site, are potent LSD1-selective inhibitors.

PMID- 29198866
TI  - Effect of side chain hydrophobicity and cationic charge on antimicrobial activity
      and cytotoxicity of helical peptoids.
AB  - Peptoids are peptidomimetic polymers that are resistant to proteolysis and less
      prone to immune responses; thus, they can provide a practical alternative to
      peptides. Among the various therapeutic applications that have been explored,
      cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial
      activity, including activity towards drug-resistant bacterial strains. While
      their potency and activity spectrum can be manipulated by sequence variations,
      bacterial selectivity and systemic toxicity need to be improved for further
      clinical development. To this aim, we incorporated various hydrophobic or
      cationic residues to improve the selectivity of the previously developed
      antibacterial peptoid 1. The analogs with hydrophobic residues demonstrated non
      specific cytotoxicity, while those with an additional cationic residue showed
      improved selectivity and comparable antibacterial activity. Specifically,
      compared to 1, peptoid 7 showed much lower hemolysis and cytotoxicity, while
      maintaining the antibacterial activity. Therefore, we believe that peptoid 7 has
      the potential to serve as a promising alternative to current antimicrobial
      therapies.

PMID- 29198867
TI  - Design and synthesis of novel pyrimidine analogs as highly selective, non
      covalent BTK inhibitors.
AB  - BTK is a promising target for the treatment of multiple diseases such as B cell
      malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a
      series of novel pyrimidine analogs as potent, highly selective, non-covalent
      inhibitors of BTK. Compound 25d demonstrated higher affinity to an unactivated
      conformation of BTK that resulted in an excellent kinase selectivity. Compound
      25d showed a good oral bioavailability in mice, and significantly inhibits the
      PCA reaction in mice.

PMID- 29198868
TI  - An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)
      analysis of hospitalization, functional status, and mortality after mechanical
      circulatory support in adults with congenital heart disease.
AB  - BACKGROUND: Adult congenital heart disease (ACHD) prevalence is increasing
      worldwide, with advanced heart failure (HF) as a leading cause of death. Limited
      data are available on durable mechanical circulatory support (MCS) in ACHD
      patients. METHODS: ACHD patients from the Interagency Registry for Mechanically
      Assisted Circulatory Support (INTERMACS) database were identified and propensity
      matched with non-ACHD patients using risk factors from the INTERMACS Seventh
      Annual Report. We compared these groups for the primary outcome of post-MCS
      mortality. We also investigated adverse event rates, functional status, and
      health-related quality of life. RESULTS: ACHD (n = 128) and non-ACHD (n = 512)
      patients were appropriately matched by baseline characteristics. ACHD patients
      had a longer length of stay at MCS implant (24 vs 19 days, p = 0.006) but similar
      rates of post-MCS adverse events and hospitalization. There were similar
      improvements in functional status and health related quality of life post-MCS in
      both groups. ACHD patients had significantly higher mortality post-MCS
      exclusively during the first 5 months after implant (p = 0.003) and a lower
      probability of receiving a transplant (p = 0.003). Risk factors for early
      mortality were biventricular or total artificial heart device implant and age >
      50 years. CONCLUSIONS: ACHD patients experience a higher early mortality after
      MCS but have similar adverse event rates and similar improvements in functional
      capacity and quality of life compared with non-ACHD patients. These data support
      expansion of MCS use in selected ACHD patients.

PMID- 29198869
TI  - The ratio of circulating regulatory cluster of differentiation 4 T cells to
      endothelial progenitor cells predicts clinically significant acute rejection
      after heart transplantation.
AB  - BACKGROUND: The aim of this study was to determine the value of the ratio of the
      percentage of circulating regulatory cluster of differentiation 4 T cells
      (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC
      ratio) for predicting clinically significant acute rejection. METHODS: Peripheral
      blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using
      flow cytometry at a mean of 42 +/- 13 days after transplant. The primary end
      point was clinically significant acute rejection, defined as an event that led to
      an acute augmentation of immunosuppression in conjunction with an International
      Society for Heart and Lung Transplantation grade >= 2R in a right ventricular
      endomyocardial biopsy specimen or non-cellular rejection (specimen-negative
      rejection) with hemodynamic compromise (decrease in left ventricular ejection
      fraction by > 25%). RESULTS: Significant rejection occurred in 27 recipients
      (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months).
      The mean %Tregs and %EPCs were not significantly different between those with and
      without an episode of significant rejection, but the mean Treg/EPC ratio was
      significantly lower in recipients with significant rejection (44.9 vs 106.7, p =
      0.001). Receiver operating characteristic curve analysis showed an area under the
      curve value for significant rejection for a Treg/EPC ratio of 0.712. The best
      cutoff value of the Treg/EPC ratio that distinguished between those with or
      without significant rejection was <= 18 by receiver operating characteristic
      curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC
      ratio of <= 18 had a significantly higher rate of rejection than those with a
      Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio
      was an independent predictor of significant rejection. CONCLUSIONS: A low
      Treg/EPC ratio measured soon after heart transplantation is an independent
      predictor of acute rejection. The Treg/EPC ratio has potential as an early
      biomarker after heart transplantation for predicting acute rejection.

PMID- 29198870
TI  - Targeting resolution of pulmonary edema in primary graft dysfunction after lung
      transplantation: Is inhaled AP301 the answer?

PMID- 29198871
TI  - Trends in Opioid Utilization Before and After Total Knee Arthroplasty.
AB  - BACKGROUND: Opioids are a mainstay in perioperative pain management among
      patients undergoing total knee arthroplasty (TKA). However, patterns in opioid
      use before and after TKA have not been well-studied. The objectives of this study
      are to characterize prescribing trends preoperatively and postoperatively and
      identify risk factors for chronic postoperative opioid use. METHODS: A review of
      the prescription-tracking database of a large private payer from 2007 to 2013 was
      performed using International Classification of Diseases, Ninth Revision and
      Current Procedural Terminology codes. Chronic opioid use was defined as opioid
      prescriptions over 6 contiguous months postoperatively. RESULTS: We identified
      66,950 patients who underwent TKA with minimum 2-year follow-up and medication
      codes. Of those taking opioids preoperatively (n = 36,668), 34.8% became chronic
      users postoperatively compared to only 5.0% of the opioid-naive cohort (n =
      30,282). Major risk factors for chronic postoperative opioid use included
      preoperative opioid use (relative risk [RR] 3.75, 95% confidence interval [CI]
      3.59-3.93), female gender (RR 1.23, 95% CI 1.20-1.25), and younger age (<=44 vs
      >=60: RR 1.41, 95% CI 1.32-1.49; 45-59 vs >=60: RR 1.42, 95% CI 1.40-1.46). From
      2007 to 2013, there was a significant linear increase in opioid use
      preoperatively (odds ratio [OR] 1.04, 95% CI 1.03-1.05, P < .001) and
      postoperatively (OR 1.20, 95% CI 1.18-1.21, P < .001), but chronic postoperative
      opioid use increased only marginally (OR 1.01, 95% CI 1.00-1.02, P = .021).
      CONCLUSION: The greatest risk factors for chronic postoperative opioid use were
      preoperative use, younger age, female gender, greater length of stay, and worse
      health status. Although the use of opioids continues to grow significantly
      preoperatively and postoperatively, chronic opioid use post-TKA has remained
      clinically unchanged.

PMID- 29198872
TI  - A Randomized Non-Inferiority Trial of Adductor Canal Block for Analgesia After
      Total Knee Arthroplasty: Single Injection Versus Catheter Technique.
AB  - BACKGROUND: Adductor canal blocks (ACBs) provide effective analgesia following
      total knee arthroplasty. We hypothesized that ACB single injection plus
      intravenous (IV) dexamethasone (Dex) shows non-inferiority to catheter, while ACB
      single injection does not. METHODS: One hundred eighty patients were randomized
      and 177 analyzed from among 1 of 3 ACB interventions: (1) 0.5% ropivacaine 20 mL;
      (2) 0.5% ropivacaine 20 mL plus IV Dex 8 mg; (3) 0.5% ropivacaine 20 mL followed
      by continuous infusion of 0.2% ropivacaine at 5 mL/h for 48 hours. The primary
      endpoint was cumulative opioid consumption at 24 hours in oral morphine
      equivalents, with a non-inferiority limit of 30 mg. Secondary endpoints included
      opioid consumption at 12 and 48 hours, rest pain scores, quality of recovery
      survey, length of stay, and anti-emetic usage. RESULTS: For 24-hour opioid
      consumption, single injection ACB with and without IV Dex had a mean difference
      of -24.2 mg (confidence interval [CI] 0.5 to -48.9, P < .001) and -21 mg (CI 3.2
      to -45.1, P < .001) relative to catheter, demonstrating non-inferiority. Non
      inferiority was also shown at 12 hours by Dex and single injection over catheter
      with mean difference of -20.4 mg (CI -6.8 to -33.9, P < .001) and -15.1 mg (CI 
      2.1 to -28.2, P < .001), respectively. No intergroup difference was found for 48
      hour opioid consumption. No differences in other secondary outcomes were observed
      across the 3 groups. CONCLUSION: Single injection ACB, with and without IV Dex,
      is non-inferior to ACB catheters in 24-hour opioid consumption, and may be
      attractive options for early-discharge, fast-track total knee arthroplasty.

PMID- 29198873
TI  - Short and Long-Term Postoperative Complications Following Total Joint
      Arthroplasty in Patients With Human Immunodeficiency Virus, Hepatitis B, or
      Hepatitis C.
AB  - INTRODUCTION: Due to advancement in treatment against human immunodeficiency
      virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), the prevalence
      of this patient population electing to undergo total joint arthroplasty (TJA) is
      increasing. Current literature is scarce and conflicting especially when
      evaluating long-term surgical complications. The purpose of this study is to
      assess the postoperative medical and surgical complications following TJA in
      these patient populations. METHODS: Using a nationwide database between 2005 and
      2012, 4 cohorts were created: patients with HIV, HCV, HBV, and HIV and HBV or HCV
      who underwent TJA. Cohorts were matched to a control group by age, gender, and
      Charlson Comorbidity Index. Thirty-day and 90-day medical complications and 90
      day and 2-year surgical complications were evaluated using odds ratios with 95%
      confidence intervals. RESULTS: Following TJA, patients with HCV or HBV had
      increased risk of pneumonia, sepsis, joint infection, and revision surgery at 90
      days and 2 years. Patients with HIV did not have increased risk of infection at
      90 days and 2 years but did have increased risk of revision at 90 days (odds
      ratio 3.21, 95% confidence interval 1.31-7.84) following total hip arthroplasty.
      CONCLUSIONS: Patients with HIV, HBV, or HCV have an overall increased risk of
      postoperative medical and surgical complications following TJA. Patients with HBV
      or HCV are at risk of more complications than patients with HIV especially for
      infection within 90 days after TJA. Patients with HIV are at risk of mechanical
      complications but do not appear to be at significant risk for infection following
      total hip arthroplasty.

PMID- 29198874
TI  - Influence of Prior Hip Salvage Surgery on Outcomes After Total Hip Arthroplasty
      in Young Patients.
AB  - BACKGROUND: As the indications for total hip arthroplasty (THA) have expanded,
      this procedure is being increasingly performed in young patients. Oftentimes,
      this population has undergone one or more salvage procedures in an attempt to
      delay or forestall a THA. However, it is unclear whether patients with prior
      salvage procedure have higher risk of adverse events. METHODS: From 2004 to 2014,
      215 THAs performed in patients less than 30 years at a single institution were
      identified. These patients were screened to identify 37 THAs in which one or more
      salvage procedures were performed prior to the THA (salvage group). The prior
      salvage procedures were open in 30 (pelvic osteotomy = 5, femoral osteotomy = 15,
      combined osteotomy = 2, core decompression = 7, bone graft = 1) and arthroscopic
      in 7. Medical and surgical complications within 90 days and overall survivorship
      at a minimum follow-up of 2 years were recorded. Nonparametric tests and Kaplan
      Meier survival curves were used to compare the groups. RESULTS: Salvage group had
      a higher rate of wound complications (P = .037), superficial infections (P =
      .005), and reoperations (P = .015). The 5-year survivorships in the salvage and
      nonsalvage groups were 97.1% and 96.7%, respectively (P = .787). CONCLUSION:
      Patients less than 30 years who undergo THA after a previous salvage procedure
      have a higher risk of wound complications, superficial infections, and
      reoperations, but similar survivorship, compared to those who did not have any
      prior salvage procedures. This information is helpful in counseling young
      patients while offering various surgical options for the management of various
      hip pathologies.

PMID- 29198876
TI  - Corrigendum to "Lipopolysaccharides detection on a grating-coupled surface
      plasmon resonance smartphone biosensor" [Biosens. Bioelectron. 99 (2018) 312
      317].

PMID- 29198875
TI  - Gancao-Gansui combination impacts gut microbiota diversity and related metabolic
      functions.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The theory of "eighteen incompatible medicaments"
      (EIM) in traditional Chinese medicine (TCM) is the most representative case of
      herbal-herbal interactions. Gancao and Gansui are one of the incompatible herbal
      pairs in EIM. Gancao, also known as "licorice", is the most frequently used
      Chinese herb or food additive. Gansui, the root of Euphorbia kansui T.P. Wang, is
      another famous Chinese herb usually used to treat edema, ascites and asthma but
      could induce gastrointestinal (GI) tract irritation. Although Gancao and Gansui
      are incompatible herbal pairs, they are still used in combination in the famous
      "Gansui-Banxia" decoction. AIM OF THE STUDY: This study was conducted to
      investigate if Gancao-Gansui combination could exacerbate Gansui induced GI tract
      injury. Moreover, the impact of Gancao-Gansui combination to gut microbiota and
      related metabolism pathways were evaluated. MATERIALS AND METHODS: Normal mice
      were divided into different groups and treated with Gancao extracts, Gansui
      extracts, and Gancao-Gansui combination extracts for 7 days. Serum biomarkers
      (diamine oxidase activity, lipopolysaccharide, motilin, IL-1beta, IL-6, TNF
      alpha) were determined to reflect GI tract damage. Gut microbiota diversity was
      studied by 16S rDNA sequencing and metagenomes analysis were also conducted to
      reflect functional genes expression alteration. Fecal hydrogen sulfide
      concentrations were measured by spectrophotometry to confirm the alteration of
      Desulfovibrio genus. Fecal lipid metabolomics study was conducted by GC-MS
      analysis to confirm the change of metagenomes and Mycoplasma abundance. RESULTS:
      Gancao-Gansui combination did not exacerbate GI tract tissue or functional damage
      but caused gut microbiota dysbiosis and increased some rare genus's abundance
      including Desulfovibrio and Mycoplasma. Desulfovibrio genus proliferation was
      confirmed by the disturbance of fecal hydrogen sulfide homeostasis. Gancao-Gansui
      combination also dys-regulated the metabolic genes in metagenomes. Mycoplasma
      genus proliferation and the metagenomes changes were both confirmed by metabolic
      profile analysis of fecal lipids, especially cholesterol. CONCLUSIONS: Gancao
      Gansui combination can impact the gut microbiota diversity and related metabolic
      functions. Further studies should be carried out when the combination of Gancao
      Gansui is used in herbal formulations as this may alter the diversity of the
      microbiota.

PMID- 29198877
TI  - The Future Role of the United States in Global Health: Emphasis on Cardiovascular
      Disease.
AB  - U.S. global health investment has focused on detection, treatment, and
      eradication of infectious diseases such as tuberculosis, malaria, and human
      immunodeficiency virus/acquired immunodeficiency syndrome, with significant
      results. Although efforts should be maintained and expanded to provide ongoing
      therapy for chronic infectious disease, there is a pressing need to meet the
      challenge of noncommunicable diseases, which constitute the highest burden of
      diseases globally. A Committee of the National Academies of Sciences,
      Engineering, and Medicine has made 14 recommendations that require ongoing
      commitments to eradication of infectious disease and increase the emphasis on
      chronic diseases such as cardiovascular disease. These include improving early
      detection and treatment, mitigating disease risk factors, shifting global health
      infrastructure to include management of cardiovascular disease, developing global
      partners and private-public ventures to meet infrastructure and funding
      challenges, streamlining medical product development and supply, increasing
      research and development capacity, and addressing gaps in global political and
      institutional leadership to meet the shifting challenge.

PMID- 29198878
TI  - Medication adherence among patients with gout: A systematic review and meta
      analysis.
AB  - OBJECTIVE: In the management of chronic gout, a large proportion of patients need
      long-term management with urate lowering therapy (ULT). This study reviews
      medication adherence to ULT and summarizes factors associated with adherence.
      METHODS: We performed a systematic literature search for studies on adherence to
      ULT among gout patients in PubMed, Embase, CINAHL, and PsycINFO. We conducted
      meta-analysis, with a random effect model, for the studies reporting the
      proportion of patients considered adherent to at least 80% of prescribed
      medication or time taken. We explored potential sources of heterogeneity,
      including geographic area and measure of adherence. Narrative summaries were made
      for data on adherence assessed/defined by Medication Event Monitoring System
      (MEMS)/pill-count or patient-reported, occurrence of a gap in therapy >=30 days
      (non-persistence), and factors associated with adherence. RESULTS: Of the 24
      studies, 16 assessed adherence using prescription/claims data, two by the MEMS or
      pill count, and six by patient-reported data. The pooled proportion of adherent
      patients (n = 13) was 46% (95% CI: 41-51); 45% across studies conducted in the
      USA (n = 8) and 48% in other countries (n = 5). Adherence assessed by MEMS/pill
      count and patient-reported was much higher than by studies using
      prescription/claims data. Non-persistence (n = 6) ranged from 54% to 87%. Factors
      associated with adherence were investigated in 18 studies. Strong evidence for a
      positive association with older age, more comorbidities, and the presence of
      diabetes or hypertension was found. CONCLUSION: Medication adherence to ULT among
      gout patients was poor. Better insight into reasons and consequences or poor
      adherence is needed.

PMID- 29198879
TI  - Radiation therapy improves disease-specific survival in women with Stage II
      endometrioid endometrial cancer-Brachytherapy may be sufficient.
AB  - PURPOSE: To evaluate disease-specific survival (DSS) outcomes in Stage II
      endometrioid endometrial cancer (EC) patients based on pathology and treatment
      information including adjuvant radiotherapy and lymph node assessment. METHODS
      AND MATERIALS: Using the Surveillance, Epidemiology, and End Results database,
      2877 patients with Stage II EC diagnosed between 2004 and 2012 treated with
      radiation were identified. DSS was determined for different modalities of
      radiation. Kaplan-Meier estimates of survival and Cox regression modeling were
      used to explore the risk associated with various factors on DSS. RESULTS: The 4
      year DSS for the study population was 90%. Radiation was associated with improved
      4-year DSS when compared to no radiotherapy (p = 0.03). Patients with Grade 2 and
      3 tumors had improved 4-year DSS with radiation (94% vs. 90%, p = 0.02 and 81%
      vs. 73%, p = 0.15), respectively, but no differences in DSS when vaginal
      brachytherapy alone was compared with external beam alone or both. Patients with
      Grade 2 (p = 0.002) and Grade 3 (p < 0.001) tumors without a lymph node
      dissection (LND) had worse DSS compared to patients with any LND. Patients with
      Grade 3 tumors without an LND who received radiation showed improved DSS (p =
      0.008). Multivariable analysis revealed that age >60 years (p < 0.001), Grade 3
      (p < 0.001), no radiotherapy (p = 0.05), and no LNDs (p < 0.001) were significant
      prognostic factors for worse DSS. CONCLUSIONS: Adjuvant radiation, whether
      delivered by brachytherapy or external beam radiation, is associated with
      improved DSS in Stage II EC patients with high-grade tumors, therefore
      brachytherapy may be sufficient.

PMID- 29198880
TI  - AureoWiki  The repository of the Staphylococcus aureus research and annotation
      community.
AB  - In light of continuously accumulating data and knowledge on major human
      pathogens, comprehensive and up-to-date sources of easily accessible information
      are urgently required. The AureoWiki database (http://aureowiki.med.uni
      greifswald.de) provides detailed information on the genes and proteins of
      clinically and experimentally relevant S. aureus strains, currently covering NCTC
      8325, COL, Newman, USA300_FPR3757, and N315. By implementing a pan-genome
      approach, AureoWiki facilitates the transfer of knowledge gained in studies with
      different S. aureus strains, thus supporting functional annotation and better
      understanding of this organism. All data related to a given gene or gene product
      is compiled on a strain-specific gene page. The gene pages contain sequence-based
      information complemented by data on, for example, protein function and
      localization, transcriptional regulation, and gene expression. The information
      provided is connected via links to other databases and published literature.
      Importantly, orthologous genes of the individual strains, which are linked by a
      pan-genome gene identifier and a unified gene name, are presented side by side
      using strain-specific tabs. The respective pan-genome gene page contains an
      orthologue table for 32 S. aureus strains, a multiple-strain genome viewer, a
      protein sequence alignment as well as other comparative information. The data
      collected in AureoWiki is also accessible through various download options in
      order to support bioinformatics applications. In addition, based on two large
      scale gene expression data sets, AureoWiki provides graphical representations of
      condition-dependent mRNA levels and protein profiles under various laboratory and
      infection-related conditions.

PMID- 29198881
TI  - Role of arsenic exposure in adipose tissue dysfunction and its possible
      implication in diabetes pathophysiology.
AB  - Exposure to arsenic in drinking water can stimulate a diverse number of diseases
      that originate from impaired lipid metabolism in adipose and glucose metabolism,
      leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and
      mediates insulin resistance with diminutive information on arsenicosis on lipid
      storage and lipolysis. This review focused on different mechanisms and pathways
      involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced
      diabetes. Though arsenic is known to cause type2 diabetes through different
      mechanisms, the role of adipose tissue in causing type2 diabetes is still
      unclear. With the existing literature, this review exhibits the effect of arsenic
      on adipose tissue and its signalling events such as SIRT3- FOXO3a signalling
      pathway, Ras -MAP -AP-1 cascade, PI(3)-K-Akt pathway, endoplasmic reticulum
      stress protein, C/EBP homologous protein (CHOP10) and GPCR pathway with role of
      adipokines. There is a need to elucidate the different types of adipokines which
      are involved in arsenic-induced diabetes. The exhibited information brings to
      light that arsenic has negative effects on a white adipose tissue (WAT) by
      decreasing adipogenesis and enhancing lipolysis. Some of the epidemiological
      studies show that arsenic would causes obesity. Few studies indicate that arsenic
      might induces lipodystrophy condition. Further research is needed to evaluate the
      mechanistic link between arsenic and adipose tissue dysfunction which leads to
      insulin resistance.

PMID- 29198882
TI  - Adjuvant effect of short chain triacylglycerol tributyrin on a mouse contact
      hypersensitivity model.
AB  - Little attention has been paid to chemicals that can enhance hypersensitivity
      caused by other chemicals. We have demonstrated that phthalate esters with short
      chain alcohols enhance fluorescein isothiocyanate (FITC)-induced contact
      hypersensitivity (CHS) in a mouse model. Furthermore, phthalate esters with such
      an enhancing effect were found to activate transient receptor potential ankyrin 1
      (TRPA1) cation channels, which are expressed on a part of sensory neurons, using
      a TRPA1-expressing cell line. In this study, we examined these activities of
      esters comprising glycerol and a short chain fatty acid, i.e. dibutyrin and
      tributyrin. We carried out chemical synthesis of dibutyrin isomers. Each
      dibutyrin isomer weakly activated TRPA1 and slightly enhanced skin sensitization
      to FITC. Unexpectedly, TRPA1 activation and enhancement of FITC-CHS were much
      more evident in the presence of tributyrin. Mechanistically, tributyrin induced
      increased dendritic cell trafficking from the skin to draining lymph nodes.
      Tributyrin enhanced interferon-gamma (IFN-gamma) production by draining lymph
      nodes, while its effect on interleukin-4 (IL-4) production was relatively less
      prominent. These results suggested that tributyrin concomitantly caused TRPA1
      activation and an adjuvant effect on FITC-CHS.

PMID- 29198883
TI  - Disease burden of knee osteoarthritis patients with a joint replacement compared
      to matched controls: a population-based analysis of a Dutch medical claims
      database.
AB  - OBJECTIVE: On a population level, the incidence of knee prostheses (KPs) has
      increased, but excess health care costs per patient, compared to matched controls
      without a KP, in the years surrounding these procedures and their determinants
      are largely unknown. We therefore aimed to provide estimates of age- and sex
      specific incidence of KPs, revision KPs, and prosthesis complications in patients
      with knee osteoarthritis (OA) and to determine excess health care costs in the
      years surrounding surgery compared with matched controls. METHODS: All KPs in OA
      patients in the Achmea Health Database were identified as well as up to four
      controls. Incidence rates of KPs, revisions, and complications from 2006 to 2013
      were determined. Annual health care cost and excess costs (over matched controls)
      preceding, during, and after surgery were calculated and their determinants were
      evaluated. RESULTS: The increased incidence of KPs, revisions, and complications
      was strongest in younger age categories and men. The average costs per patient
      were relatively stable between 2006 and 2012. KP patient's annual health care
      costs increased towards the year of surgery. After surgery, costs decreased, but
      remained higher as compared to costs prior to surgery. High post-surgery costs
      were mainly associated with subsequent revisions or additional KPs, but costs
      were also higher in females, lower age categories, and lower social economic
      status. CONCLUSION: These results underscore the increasing burden and medical
      need associated with end-stage OA, especially in younger age categories.
      Improvement of guidelines tailored to individual patient groups aimed at avoiding
      complications and revisions is required to counteract this increasing burden.

PMID- 29198884
TI  - Perihepatitis at the onset of Behcet's disease: A case report.

PMID- 29198885
TI  - Atypical juxta-articular form of Dercum's disease in a patient treated with
      tocilizumab for rheumatoid arthritis.

PMID- 29198886
TI  - Remaining local subclinical joint inflammation is associated with deteriorated
      metacarpeal head bone microarchitecture in rheumatoid arthritis patients low
      disease activity.
AB  - OBJECTIVES: Bone alterations at the subchondral level during rheumatoid arthritis
      (RA) remain under investigation. It remains unknown whether subchondral bone
      damage might still occur in RA patients in clinical remission, which could then
      infer suggesting that even minor subclinical inflammatory changes in the joint
      can induce local bone loss. METHODS: Thirty-two RA patients treated with
      biological disease-modifying anti-rheumatic drugs (bDMARDs) with low disease
      activity since at least 6 months and having erosion on the second or third
      metacarpeal head were enrolled in this pilot cross-sectional study. They were
      divided in two groups according to local inflammation assessed by Doppler
      ultrasound exam surrounding the site of erosion. Cortical and trabecular
      parameters of the metacarpeal head were then assessed by high-resolution
      peripheral quantitative computed tomography (HR-pQCT) and compared in both
      groups. RESULTS: Twenty and twelve RA patients were enrolled in the "Doppler
      positive erosion" (DE+) group and Doppler negative erosion (DE-) group,
      respectively. No difference was observed in their clinical or biological RA
      characteristics. Both cortical density and thickness were similar among groups.
      Within the trabecular network, while no difference in bone volume was observed,
      trabecular density as well as trabecular number were decreased (P<0.001 and
      P<0.05 respectively), whereas trabecular separation and distribution of
      trabecular separation were increased in DE+ compared to DE- (P<0.05). CONCLUSION:
      In RA patients in low disease activity under bDMARDs, persistence of local
      inflammation was associated with alteration of the trabecular compartment.
      Trabecular density was the most strongly altered parameter and could be a
      candidate to assess drug effect on periarticular bone damage.

PMID- 29198887
TI  - A novel catalytic ceramic membrane fabricated with CuMn2O4 particles for emerging
      UV absorbers degradation from aqueous and membrane fouling elimination.
AB  - A novel catalytic ceramic membrane (CM) for improving ozonation and filtration
      performance was fabricated by surface coating CuMn2O4 particles on a tubular CM.
      The degradation of ultraviolet (UV) absorbers, reduction of toxicity, elimination
      of membrane fouling and catalytic mechanism were investigated. The
      characterization results suggested the particles were well-fixed on membrane
      surface. The modified membrane showed improved benzophenone-3 removal performance
      (from 28% to 34%), detoxification (EC50 as 12.77%) and the stability of catalytic
      activity. In the degradation performance of model UV absorbers, the developed
      membrane significantly decreased the UV254 and DOC values in effluent. Compared
      with a virgin CM, this CM ozonation increased water flux as 29.9% by in-situ
      degrade effluent organic matters. The CuMn2O4 modified membrane enhanced the
      ozone self-decompose to generate O2- and initiated the chain reaction of ozone
      decomposition, and subsequently reacted with molecule ozone to produce OH.
      Additionally, CM was able to promote the interaction between ozone and
      catalyst/organic chemicals to form H2O2 that promoted the formation of OH. This
      catalytic ceramic membrane combining with ozonation showed potential applications
      in emerging pollutant degradation and membrane fouling elimination, and acted as
      a novel ternary technology for wastewater treatment and water reuse.

PMID- 29198888
TI  - Salvage Therapy for Brain Arteriovenous Malformations After Failure of Gamma
      Knife Stereotactic Radiosurgery.
AB  - OBJECTIVE: The aim of this study was to investigate delayed complications in
      patients with brain arteriovenous malformation (BAVM) after Gamma Knife
      stereotactic radiosurgery and to present the salvage therapy experiences of
      patients with BAVM with radiation-induced changes (RICs) or intracranial
      hemorrhage (ICH). METHODS: This cohort consisted of 44 patients with BAVM who
      underwent failed GKRS between 2000 and 2015. These patients were further divided
      into an RIC group (23 patients) and an ICH group (21 patients) based on their
      post-GKRS complications. The patients' characteristics, treatment strategies, and
      long-term outcomes were analyzed. The modified Rankin Scale was used to assess
      the neurologic status of each patient. RESULTS: In our study, the marginal dose
      and radiosurgery-based arteriovenous malformation score were not significantly
      different between the 2 groups. Craniotomy was performed in 26 patients (9
      patients with ICH and 17 patients with RICs), and histologic examination showed
      cavernous angioma changes in 6 patients. In addition, 6 patients underwent repeat
      radiosurgery in the ICH group, and 7 patients used bevacizumab in the RIC group.
      Thirty patients showed good outcomes at the last follow-up (modified Rankin Scale
      score <3). CONCLUSIONS: Salvage therapy for patients with BAVM should be
      performed based on the latency period and lesion characteristics of each
      individual. Prompt treatment and a longer follow-up are recommended to achieve
      good clinical outcomes.

PMID- 29198889
TI  - Virtual Reality-Based Simulators for Cranial Tumor Surgery: A Systematic Review.
AB  - BACKGROUND: Virtual reality (VR) simulators have become useful tools in various
      fields of medicine. Prominent uses of VR technologies include assessment of
      physician skills and presurgical planning. VR has shown effectiveness in multiple
      surgical specialties, yet its use in neurosurgery remains limited. OBJECTIVE: To
      examine all current literature on VR-based simulation for presurgical planning
      and training in cranial tumor surgeries and to assess the quality of these
      studies. METHODS: PubMed and Embase were systematically searched to identify
      studies that used VR for presurgical planning and/or studies that investigated
      the use of VR as a training tool from inception to May 25, 2017. RESULTS: The
      initial search identified 1662 articles. Thirty-seven full-text articles were
      assessed for inclusion. Nine studies were included. These studies were subdivided
      into presurgical planning and training using VR. CONCLUSIONS: Prospects for VR
      are bright when surgical planning and skills training are considered. In terms of
      surgical planning, VR has noted and documented usefulness in the planning of
      cranial surgeries. Further, VR has been central to establishing reproducible
      benchmarks of performance in relation to cranial tumor resection, which are
      helpful not only in showing face and construct validity but also in enhancing
      neurosurgical training in a way not previously examined. Although additional
      studies are needed to better delineate the precise role of VR in each of these
      capacities, these studies stand to show the usefulness of VR in the neurosurgery
      and highlight the need for further investigation.

PMID- 29198890
TI  - Evaluation of Patency After Vascular Anastomosis Using Quantitative Evaluation of
      Visualization Time in Indocyanine Green Video Angiography.
AB  - BACKGROUND: In vascular reconstructive surgery, intraoperative confirmation of
      patency is performed by angiography, Doppler, or indocyanine videoangiography,
      but it is sometimes insufficient. OBJECTIVE: Using the FLOW 800 system (Carl
      Zeiss, Oberkochen, Germany), we confirmed patency in a quantitative relative
      evaluation of the timing of the luminance change of the regions of interest
      (ROIs) on the donor and recipient. METHODS: Thirty-seven patients (58
      anastomoses) were divided into 2 groups: those with arteriosclerotic ischemic
      disease (CI group; n = 23) and those with cerebral aneurysm (AN group; n = 14).
      Four ROIs were set: the donor, proximal, and distal sides of the recipient middle
      cerebral artery (MCA) and cortical MCA (control MCA). The half-life for
      fluorescence intensity was calculated by using the FLOW 800 system. A delay map
      analysis was also performed. RESULTS: In the CI group, there were statistically
      significant differences (P < 0.05) between the donor vessel and control MCA,
      proximal MCA and MCA control, and distal MCA and control MCA. The investigation
      with the delay map showed red tones in 20/22 patients in the CI group and in 2/17
      patients in the AN group. CONCLUSIONS: In the CI group, the transit time of the
      donor vessel was shown relatively early as red T. When good patency has been
      achieved, the FLOW 800 system can be used to confirm patency more reliably,
      especially in ischemic regions. The unique point of this research is that the
      patency of anastomotic vessels was evaluated as a quantitative value of its
      rendering time rather than as a change in fluorescence intensity.

PMID- 29198891
TI  - Observing the advanced disease course in mucopolysaccharidosis, type IIIA; a case
      series.
AB  - This follow-up study of a subgroup of the patients seen in a natural history
      study of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A) addressed
      the adaptive and medical characteristics of their advanced disease
      manifestations. Of the original 24 patients, specific data was collected on only
      58% primarily due to difficulty in locating families and coordinating time for
      interviews two to four years after the original study. At the last contact with
      the patient, age range was 8 to 24years of age. Data were collected from
      telephone interviews from the Vineland Adaptive Behavior Scales II and medical
      and treatment history. We report the case data from rapid progressing and slow
      progressing patients separately. By the end of our data collection, 5 patients
      had died; 4 rapid progressing patients between 8 and 12years of age and 1 slow
      progressing patient at age 21. Two patients were in out-of-home placements in the
      year before they died. We found that the incidence of surgeries and epilepsy was
      relatively low and that behavior problems largely subsided. Adaptive levels were
      very low with children functioning at below a two-year age equivalent level in
      all adaptive functions, but motor skills were slightly more intact. Only one slow
      progressing patient was functioning above a three-year level. Parent burden had
      shifted from behavioral control to physical management. Although their quality of
      life was clearly negatively impacted by physical management and palliative care,
      parents were more able to cope and adapt to such demands than in the initial
      stages of the disease.

PMID- 29198892
TI  - RTB lectin-mediated delivery of lysosomal alpha-l-iduronidase mitigates disease
      manifestations systemically including the central nervous system.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal disease resulting from
      deficiency in the alpha-L-iduronidase (IDUA) hydrolase and subsequent
      accumulation of glycosaminoglycan (GAG). Clinically, enzyme replacement therapy
      (ERT) with IDUA achieves negligible neurological benefits presumably due to blood
      brain-barrier (BBB) limitations. To investigate the plant lectin ricin B chain
      (RTB) as a novel carrier for enzyme delivery to the brain, an IDUA:RTB fusion
      protein (IDUAL), produced in N. benthamiana leaves, was tested in a murine model
      of Hurler syndrome (MPS I). Affect mice (n=3 for each group) were intravenously
      injected with a single dose of IDUAL (0.58, 2 or 5.8mgIDUAequivalents/kg) and
      analyzed after 24h. IDUA activities in liver, kidney and spleen increased
      significantly, and liver GAG levels were significantly reduced in all three
      groups. Plasma IDUA levels for all treated groups were high at 1h after injection
      and decreased by 95% at 4h, indicating efficient distribution into tissues. For
      long-term evaluations, IDUAL (0.58 or 2mg/kg, 8 weekly injections) was
      intravenously injected into MPS I mice (n=12 for each group). Thirteen days after
      the 8th injection, significant IDUA activity was detected in the liver and
      spleen. GAG levels in tissues including the brain cortex and cerebellum were
      significantly reduced in treated animals. Treated MPS I mice also showed
      significant improvement in neurocognitive testing. ELISA results showed that
      while there was a significant antibody response against IDUAL and plant-derived
      IDUA, there was no significant antibody response to RTB. No major toxicity or
      adverse events were observed. Together, these results showed that infusion of
      IDUAL allowed for significant IDUA levels and GAG reduction in the brain and
      subsequent neurological benefits. This RTB-mediated delivery may have significant
      implications for therapeutic protein delivery impacting a broad spectrum of
      lysosomal, and potentially neurological diseases.

PMID- 29198893
TI  - Synthesis and anti-influenza virus evaluation of triterpene-sialic acid
      conjugates.
AB  - We are interested in new non-natural glycosides with sialic acid conjugates and
      their biological activities. We report the synthesis of eleven non-natural
      occurring glycosides, which are triterpene (glycyrrhetinic acid and its
      derivatives)-sialic acid conjugates, and their inhibitory activities against
      influenza virus sialidases and influenza virus multiplication in MDCK host cells.
      Deoxoglycyrrhetol-sialic acid conjugates (6d and 6e) and oleanolic acid-sialic
      acid conjugates (7d and 7e) showed strong inhibitory activities against three
      subtypes of influenza virus sialidases. These four compounds (6d, 6e, 7d and 7e)
      showed clear inhibition to influenza virus multiplication but not to MDCK host
      cell survival.

PMID- 29198894
TI  - Design, synthesis and biological evaluation of novel indole-xanthendione hybrids
      as selective estrogen receptor modulators.
AB  - Ground breaking clinical therapeutic advances in the treatment of breast cancer
      (BC) is the introduction of selective estrogen receptor modulators (SERMs). We
      have expeditiously designed and synthesized indole-xanthendione hybrids by
      coalescing the indole nucleus with xanthendione. All the compounds were first
      screened for anti-proliferative activity, cytotoxicity and ER-alpha binding
      affinity by utilizing ER-alpha dominant T47D BC cell lines, PBMCs and ER-alpha
      competitor assay kit. From this study, two representative compounds 6e and 6f
      showing most promising activity were advanced for gene expression studies for
      targeting ER-alpha. Cell imaging experiment undoubtedly indicate that both the
      compounds were able to cross cellular bio membrane and accumulate thus
      instigating cytotoxicity. RT-PCR and Western blotting experiments further
      strengthened that both compounds altered the expression of mRNA and receptor
      protein of ER-alpha, thereby forestalling downstream transactivation and
      signalling pathway in T47D cells line. Structural investigation from induced fit
      simulation study suggest that indole moiety of the compounds 6e and 6f helps in
      the anchoring of the xanthendione moiety in the hydrophobic region of the cavity
      thus enabling the compound to bind in antagonistic conformation similar to
      bazedoxifene by extensive hydrogen bonding and Van der Waals forces. All these
      finding collectively imply that compound 6e and 6f represents a novel potent ER
      alpha antagonist and in the development of SERMs for the management of BC.

PMID- 29198895
TI  - Portal-to-right portal vein bypass for extrahepatic portal vein obstruction.
AB  - OBJECTIVE: Rex shunt (mesenteric-to-left portal vein bypass) is considered a more
      physiologically rational treatment for EHPVO than other portosystemic systemic
      shunts in children. However, about 13.6% of children with EHPVO do not have
      usable left portal veins and up to 28.1%. Rex operations in children are not
      successful. Hence, a Rex shunt in these children was impossible. This study
      reports a novel approach by portal-to-right portal vein bypass for treatment of
      children with failed Rex shunts. MATERIAL AND METHODS: Eight children (age
      6.1years, range 3.5-8.9years) who underwent Rex shunts developed recurrent
      gastrointestinal bleeding and hypersplenism 13months (11-30months)
      postoperatively. After ultrasound confirmation of blocked shunt, they underwent
      exploration. Three patients were found to have right portal vein agenesis. Five
      patients (62.5%) were found to have the patent right portal vein, with the
      diameter of 3-6mm. Four patients underwent bypass between the main portal vein in
      the hepatoduodenal ligament and the right portal vein by interposing an inferior
      mesenteric vein autograft, whereas the remaining patient underwent a bypass using
      ileal mesenteric vein autograft. RESULTS: The operations took 2.3h (1.9-3.5h).
      The estimated blood loss was 50ml (30-80ml), with no complication. The portal
      venous pressure dropped from 34.6cmH2O (28-45 cmH2O) before the bypass to
      19.6cmH2O (14-24cmH2O) after the bypass. The 5 patients were followed up for
      10.2months (4-17months) and the post-operative ultrasound and CT angiography
      confirmed the patency of all the grafts and disappearance of the portal venous
      cavernova in all five patients. CONCLUSION: The portal-to-right portal vein
      bypass technique is feasible and safe for treatment of children with EHPVO who
      have had failed Rex shunts. Our preliminary result indicates that this technique
      extends the success of Rex shunt from left portal vein to right portal vein and
      open a new indication of physiological shunt for some of the children who not
      only have had failed Rex shunts or but also are not suitable for the Rex shunts.
      TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

PMID- 29198896
TI  - Computed tomographic imaging in the pediatric patient with a seatbelt sign: still
      not good enough.
AB  - PURPOSE: Considering the improvements in CT over the past decade, this study
      aimed to determine whether CT can diagnose HVI in pediatric trauma patients with
      seatbelt signs (SBS). METHODS: We retrospectively identified pediatric patients
      with SBS who had abdominopelvic CT performed on initial evaluation over 5
      1/2years. Abnormal CT was defined by identification of any intra-abdominal
      abnormality possibly related to trauma. RESULTS: One hundred twenty patients met
      inclusion criteria. CT was abnormal in 38/120 (32%) patients: 34 scans had
      evidence of HVI and 6 showed solid organ injury (SOI). Of the 34 with suspicion
      for HVI, 15 (44%) had small amounts of isolated pelvic free fluid as the only
      abnormal CT finding; none required intervention. Ultimately, 16/120 (13%)
      patients suffered HVI and underwent celiotomy. Three patients initially had a
      normal CT but required celiotomy for clinical deterioration within 20h of
      presentation. False negative CT rate was 3.6%. The sensitivity, specificity and
      accuracy of CT to diagnose significant HVI in the presence of SBS were 81%, 80%,
      and 80%, respectively. CONCLUSIONS: Despite improvements in CT, pediatric
      patients with SBS may have HVI not evident on initial CT confirming the need to
      observation for delayed manifestation of HVI. LEVEL OF EVIDENCE: Level II Study
      of a Diagnostic Test.

PMID- 29198897
TI  - The idle central venous catheter in the NICU: When should it be removed?
AB  - PURPOSE: There is debate regarding the optimal timing of central line removal in
      the neonatal intensive care unit (NICU). The purpose was to evaluate outcomes of
      idle peripherally inserted central catheters (PICCs) and tunneled central venous
      catheters (TCVCs) and determine the incidence of line-related infections and
      replacements. METHODS: Patients in the NICU with T-CVCs placed between 11/2008
      and 8/2015 (n=134) or PICCs placed between 7/2013 and 10/2015 (n=467) were
      included. Demographics and outcomes were compared. RESULTS: The most common
      indications for line placement were parenteral nutrition for PICCs (74%) and lack
      of access for T-CVCs (53%). T-CVCs had a greater proportion of idle days (T-CVC-
      25.2% vs PICC- 5.1%, p<0.001) and removal within 24h of discharge (T-CVC-53% vs
      PICC-5.8%, p<0.001). Conversely, 81% of PICCs were removed within 24h of nonuse.
      Line replacement after removal for nonuse was required in 6% of PICCs and zero T
      CVCs. In both groups, the central line-associated bloodstream infection (CLABSI)
      rate was lower in idle lines compared to ones in use. CONCLUSION: Patients
      treated with PICCs and T-CVCs are different populations and should have different
      guidelines for removal. In neonates with difficult access, the low risk of
      CLABSIs in idle surgically placed catheters may justify maintaining access until
      discharge. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: III.

PMID- 29198898
TI  - Levels of prebeta-1 high-density lipoprotein are elevated in 3 phenotypes of
      dyslipidemia.
AB  - BACKGROUND: Prebeta-1 high-density lipoprotein (HDL) is a small subspecies of HDL
      that functions as the HDL quantum particle and is the principal acceptor of
      cholesterol effluxed from macrophages through the ATP-binding cassette
      transporter, ABCA1. High levels of prebeta-1 HDL are associated with increased
      risk of structural coronary artery disease and myocardial infarction. OBJECTIVE:
      We aimed to compare prebeta-1 HDL levels in normal subjects and in 3 phenotypes
      of dyslipidemia. METHODS: We studied 2435 individuals (1388 women; 1047 men). Of
      these, 2018 were not taking lipid-lowering medication when enrolled: 392 were
      normolipidemic controls; 713 had elevated levels of low-density lipoprotein
      cholesterol; 623 had combined hyperlipidemia; and 290 had hypertriglyceridemia.
      RESULTS: Relative to controls, prebeta-1 HDL levels were increased in all 3
      dyslipidemic phenotypes, particularly the combined and hypertriglyceridemia
      groups. This increase possibly reflects increased acceptor capacity of
      apolipoprotein B-100 containing lipoproteins for entropically driven transfer of
      cholesteryl esters from HDL via cholesteryl ester transfer protein. Multiple
      regression analysis revealed that the main predictor variables significantly
      associated with prebeta-1 HDL levels were apolipoprotein A-I (apoA-1) (beta =
      0.500), triglyceride (beta = 0.285), HDL-C (beta = -0.237), and age (beta = 
      0.169). There was an interaction between apoA-1 and sex (female vs male; beta = 
      0.110). Among postmenopausal women, estrogenized subjects had a similar level of
      prebeta-1 HDL compared to those not receiving estrogens. CONCLUSIONS: Prebeta-1
      HDL levels are elevated in the 3 most common types of hyperlipidemia and are most
      strongly influenced by the levels of apoA-1, triglyceride, and HDL-C.

PMID- 29198900
TI  - Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor
      following Acute Stroke.
AB  - OBJECTIVES: People after stroke demonstrate alterations in vascular endothelial
      function measured by flow-mediated dilation. Limited information is available in
      the literature on possible protective factors following stroke. The aims of the
      secondary analysis were (1) to characterize the time course of vascular
      endothelial function using flow-mediated dilation at 72 hours after stroke and 1
      week later during inpatient stroke rehabilitation and (2) to determine whether
      flow-mediated dilation was related to vascular endothelial growth factor, brain
      derived neurotrophic factor, or estimated prestroke peak oxygen uptake. METHODS:
      Flow-mediated dilation using Doppler ultrasound was assessed in bilateral
      brachial arteries at the defined time points. Flow-mediated dilation and blood
      draws occurred on the same day between 7:30 am and 9:00 am following an overnight
      fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular
      endothelial growth factor and brain-derived neurotrophic factor values. A
      nonexercise estimate was used to calculate prestroke peak oxygen uptake. RESULTS:
      We have shown that between-limb differences are evident within 72 hours after
      stroke and remain 1 week later during inpatient rehabilitation. Higher values for
      vascular endothelial growth factor were associated with increased flow-mediated
      dilation at both time points. Higher estimated prestroke peak oxygen uptake was
      related to flow-mediated dilation. Brain-derived neurotrophic factor was not
      related to any outcome measures. CONCLUSIONS: Unique vascular adaptations start
      early after stroke in the stroke-affected limb and remain through inpatient
      stroke rehabilitation. Vascular endothelial growth factor and prestroke physical
      activity may have a protective role in vascular function following stroke. Future
      work should focus on mechanistic pathways for preservation of vascular health.

PMID- 29198899
TI  - Sentinel surveillance data from Eritrean migrants in Italy: The theory of
      "Healthy Migrants".
AB  - BACKGROUND: Eritrean migrants accounted for the majority of people who drowned in
      the Mediterranean this year. Recently, data deficit about international migration
      has been reported. METHODS: One hundred and thirty-three Eritrean migrants, upon
      their arrival in Italy, were accommodated at the asylum seekers center of
      Castelnuovo di Porto, together with 25 sanitary workers, and received
      microbiological surveillance at the Clinical Pathology and Microbiology Unit of
      the University Campus Bio-Medico of Rome. RESULTS: Gram-negative bacteria, mostly
      Klebsiella pneumoniae and Klebsiella oxytoca, were frequently recovered in
      surveillance swabs. Gram-positive bacteria, represented by Streptococcus
      pneumoniae, Streptococcus pyogenes, Streptococcus dysgalactiae and Staphylococcus
      aureus, were also isolated in surveillance swabs. In migrants, polymicrobial
      swabs were recovered at high frequency, and unusual microorganisms, rarely found
      in our country, were isolated. CONCLUSION: The polymicrobial colonization and the
      high prevalence of gram-negative bacteria represent the baseline characteristics
      of this migrant population from Eritrea. The presence of unusual microorganisms
      can be potentially pathogenic to asymptomatic carriers at risk of developing
      clinical disease if immunosuppressed or subjected to invasive procedures. In
      conclusion, active microbiological surveillance can represent an advantage for
      the host country in terms of data collection and by tracing unusual or resistant
      microorganisms by monitoring migrants' health status.

PMID- 29198901
TI  - Does the Primary Imaging Modality-Computed Tomography or Magnetic Resonance
      Imaging-Influence Stroke Physicians' Certainty on Whether or Not to Give
      Thrombolysis to Randomized Acute Stroke Patients?
AB  - BACKGROUND: Door-to-needle time of 20 minutes to stroke patients with intravenous
      tissue plasminogen activator (iv-tPA) is feasible when computed tomography (CT)
      is used as first-line of brain imaging. Magnetic resonance imaging (MRI)-based
      assessment is more time-consuming but superior in detecting acute ischemia. The
      certainty with which stroke physicians prescribe or refrain from giving iv-tPA
      treatment to CT- versus MRI-examined patients has not previously been studied.
      The aim of the present study was to determine the effect of a primary imaging
      strategy of CT or MRI on clinicians' certainty to prescribe or refrain from
      giving iv-tPA to patients with suspected acute stroke. METHOD: Consecutive
      patients with suspected stroke were quasi-randomized to either CT- or MRI-based
      assessment before potential iv-tPA treatment. The influence of (1) the clinical
      findings and (2) the image findings, and (3) the certainty with which the stroke
      physician prescribed or refrained from giving iv-tPA treatment were assessed with
      visual analog scales (VAS). Predictors of treatment certainty were identified
      with a random-effect model. RESULTS: Four-hundred forty-four consecutive patients
      were quasi-randomized. MRI influenced the final treatment decision more than CT
      (P = .002). Compared with CT-examined patients (mean VAS score 8.6, SD +/-1.6)
      stroke physicians were significantly more certain when prescribing or refraining
      from giving iv-tPA to MRI-examined patients (mean VAS score 9.0, SD +/-1.2) (P =
      .014). No differences in modified Rankin scale or mortality were detected at 3
      months in CT- versus MRI-examined iv-tPA-treated patients. CONCLUSIONS: Stroke
      physicians were significantly more certain when prescribing iv-tPA to MRI
      examined stroke patients, and MRI influences the final treatment decision
      significantly more compared with CT, although no difference in mortality and
      functional outcome at 3 months was detected between CT- and MRI-examined patients
      treated with iv-tPA.

PMID- 29198902
TI  - Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus
      aureus on the efficacy of cefazolin and other beta-lactams.
AB  - The existence of a cefazolin inoculum effect (InE) of methicillin-susceptible
      Staphylococcus aureus (MSSA), which is speculated to be a reason for cefazolin
      treatment failure in MSSA infections, is controversial. In Japan, although
      cefazolin is one of the therapeutic choices for patients with MSSA infection,
      there are few reports of this effect. Additionally, the association between InE
      and blaZ type in beta-lactams other than cefazolin has not been well documented.
      In this study, we confirmed an MSSA InE in several beta-lactams, including
      cefazolin, and its relationship with blaZ, using 52 MSSA isolates from blood
      cultures. Three isolates (5.8%) that possessed type A blaZ showed a pronounced
      cefazolin InE. Five isolates (9.6%) showed pronounced InE with
      sulbactam/ampicillin; four isolates had type C blaZ and one had type A blaZ.
      However, we confirmed InE in MSSA isolates with blaZ not only type A and C but
      also B and D. For cefotaxime, ceftriaxone, imipenem, and meropenem, regardless of
      the presence of blaZ, we did not observe a significant increase in MICs at a high
      inoculum of MSSA. Hence, our results suggest that the above four beta-lactams are
      good alternatives to cefazolin if InE leads to treatment failure in a patient.

PMID- 29198903
TI  - Canadian Registry of Implantable Electronic Device Outcomes: Longer-term follow
      up of the Riata lead under advisory.
AB  - BACKGROUND: The Riata lead advisory was announced in 2011 and has posed unique
      management challenges because of cable externalization and insulation abrasion,
      in some cases leading to sudden loss of defibrillation. OBJECTIVE: The purpose of
      this study was to provide further data on the rate of electrical failure in a
      population of patients with a Riata lead under advisory. METHODS: Using the
      Canadian Registry of Electronic Device Outcomes, prospective follow-up data were
      collected on 1352 Riata leads under advisory in 17 implantable cardioverter
      defibrillator (ICD) implantation centers in Canada. Data on electrical and
      structural failure were collected, as well as periprocedural complications
      related to lead revision (abandonment or extraction). RESULTS: Of the 1352 leads
      included in this 12-month follow-up cohort, 110 leads were revised. Mean follow
      up time was 10.4 +/- 1.5 years. The 12-year rate of electrical failure for the
      8Fr lead was 9.45%, whereas the 10-year failure rate for the 7Fr lead was 7.25%
      and was not found to be accelerating. Of the leads revised because of advisory
      only (patient preference, advisory related, electrical or structural failure),
      the majority were abandoned (n = 54 [76.0%]), whereas 17 (24.0%) were extracted
      using power tools. The rate of major complications in each group was 5.6% and
      5.9%, respectively. CONCLUSION: This report provides further data on the risk of
      electrical lead failure over a long lead dwell time. The risk of failure exceeds
      the risk of periprocedural major complications, indicating that the risk-to
      benefit ratio is favorable to revise the lead in appropriate clinical scenarios.

PMID- 29198904
TI  - Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl
      benzaldehyde and amines in acid medium.
AB  - We have developed a facile and efficient synthetic route to substituted
      isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a
      variety of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive
      free and takes place at reflux conditions with short reaction time to furnish
      products in good to excellent yields. All the compounds have been characterized
      by spectral techniques such as IR, 1H NMR and Mass etc. Synthesized compounds
      were evaluated for antimicrobial activity against specific bacterial like 1)
      Staphylococcus strains aureus 2) Bacillus subtilis 3) Escherichia coli 4)
      Pseudomonas aeruginosa. Compounds 3e, 3n, 3 m, 3 l, 3 k, 3j and 3b showed most
      potent in vitro activity against bacterial strains.

PMID- 29198905
TI  - The Microbiota Regulates Immunity and Immunologic Diseases in Dogs and Cats.
AB  - The complex commensal microbiota found on body surfaces controls immune responses
      and the development of allergic and inflammatory diseases. New genetic
      technologies permit investigators to determine the composition of the complex
      microbial populations found on these surfaces. Changes in the microbiota
      (dysbiosis) as a result of antibiotic use, diet, or other factors thus influence
      the development of many diseases in the dog and cat. The most important of these
      include chronic gastrointestinal disease; respiratory allergies, such as asthma;
      skin diseases, especially atopic dermatitis; and some autoimmune diseases.

PMID- 29198906
TI  - Vaccines in Shelters and Group Settings.
AB  - Dogs and cats entering animal shelters are at high risk of acquiring 1 or more
      contagious infectious diseases. Such animals may be severely stressed, exhausted,
      and unwell, as well as malnourished and parasitized. The typically high
      throughput of shelter animals, many of them young and of unknown vaccination
      status, plays a role. Vaccines are a crucially important part of the management
      approach to limiting morbidity, mortality, and spread of infection. Guidelines
      for the use of vaccines in shelters have been published and are reviewed and
      discussed in this article.

PMID- 29198907
TI  - Aquatic life in Neotropical rainforest canopies: Techniques using artificial
      phytotelmata to study the invertebrate communities inhabiting therein.
AB  - In Neotropical rainforest canopies, phytotelmata ("plant-held waters") shelter
      diverse aquatic macroinvertebrate communities, including vectors of animal
      diseases. Studying these communities is difficult because phytotelmata are widely
      dispersed, hard to find from the ground and often inaccessible. We propose here a
      method for placing in tree crowns "artificial phytotelmata" whose size and shape
      can be tailored to different research targets. The efficacy of this method was
      shown while comparing the patterns of community diversity of three forest
      formations. We noted a difference between a riparian forest and a rainforest,
      whereas trees alongside a dirt road cutting through that rainforest corresponded
      to a subset of the latter. Because rarefied species richness was significantly
      lower when the phytotelmata were left for three weeks rather than for six or nine
      weeks, we recommend leaving the phytotelmata for twelve weeks to permit predators
      and phoretic species to fully establish themselves.

PMID- 29198908
TI  - Overexpression of nuclear AR-V7 protein in primary prostate cancer is an
      independent negative prognostic marker in men with high-risk disease receiving
      adjuvant therapy.
AB  - BACKGROUND: Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7)
      has recently been reported to be associated with resistance to antihormonal
      therapy. Herein, we address the question whether tumor cells with AR-V7
      expression can be detected at the time of radical prostatectomy, that is, before
      long-term hormonal manipulation and castration resistance, and what the potential
      prognostic impact on the biochemical recurrence (BCR)-free survival may be.
      METHODS: An anti-AR-V7 antibody was first validated in a training set of prostate
      cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We
      then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph
      node metastases from 163 predominantly high-risk patients (cohort I) as well as
      the primary tumors from patients of a second, consecutive patient cohort (n =
      238, cohort II) not selected for any clinicopathological features. Staining
      results were correlated to patient characteristics and BCR-free patient survival.
      RESULTS: High nuclear AR-V7 protein expression was detected in approximately 30%
      40% of patients in cohort I and II at the time of radical prostatectomy. High
      baseline expression of nuclear AR-V7 protein was associated with an unfavorable
      BCR-free survival in the high-risk patient cohort I but not in the unselected
      consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic
      factor in high-risk prostate cancer patients of cohort I who were selected to
      receive adjuvant treatment. CONCLUSIONS: Prostate cancer cells with high nuclear
      AR-V7 protein expression can be detected in a substantial proportion of tumors at
      the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is
      associated with an unfavorable prognosis for BCR-free survival in a high-risk
      patient cohort including a subgroup of patients selected to receive adjuvant
      therapy, in which AR-V7 was an independent negative prognosticator.
      Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors with
      remarkably aggressive growth characteristics among clinically and histologically
      high-risk patients at the time of radical prostatectomy.

PMID- 29198910
TI  - Performance of Xpert MTB/RIF Ultra: a matter of dead or alive.

PMID- 29198909
TI  - HIV-1 drug resistance before initiation or re-initiation of first-line
      antiretroviral therapy in low-income and middle-income countries: a systematic
      review and meta-regression analysis.
AB  - BACKGROUND: Pretreatment drug resistance in people initiating or re-initiating
      antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income
      countries (LMICs). We aimed to assess the scale of this problem and whether it is
      associated with the intiation or re-initiation of ART in people who have had
      previous exposure to antiretroviral drugs. METHODS: This study was a systematic
      review and meta-regression analysis. We assessed regional prevalence of
      pretreatment drug resistance and risk of pretreatment drug resistance in people
      initiating ART who reported previous ART exposure. We systematically screened
      publications and unpublished datasets for pretreatment drug-resistance data in
      individuals in LMICs initiating or re-initiating first-line ART from LMICs. We
      searched for studies in PubMed and Embase and conference abstracts and
      presentations from the Conference on Retroviruses and Opportunistic Infections,
      the International AIDS Society Conference, and the International Drug Resistance
      Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of
      drug resistance within a specified region at any specific timepoint, we extracted
      study level data and pooled prevalence estimates within the region using an empty
      logistic regression model with a random effect at the study level. We used random
      effects meta-regression to relate sampling year to prevalence of pretreatment
      drug resistance within geographical regions. FINDINGS: We identified 358 datasets
      that contributed data to our analyses, representing 56 044 adults in 63
      countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were
      11.0% (7.5-15.9) in southern Africa, 10.1% (5.1-19.4) in eastern Africa, 7.2%
      (2.9-16.5) in western and central Africa, and 9.4% (6.6-13.2) in Latin America
      and the Caribbean. There were substantial increases in pretreatment NNRTI
      resistance per year in all regions. The yearly increases in the odds of
      pretreatment drug resistance were 23% (95% CI 16-29) in southern Africa, 17% (5
      30) in eastern Africa, 17% (6-29) in western and central Africa, 11% (5-18) in
      Latin America and the Caribbean, and 11% (2-20) in Asia. Estimated increases in
      the absolute prevalence of pretreatment drug resistance between 2015 and 2016
      ranged from 0.3% in Asia to 1.8% in southern Africa. INTERPRETATION: Pretreatment
      drug resistance is increasing at substantial rate in LMICs, especially in sub
      Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near
      WHO's 10% threshold for changing first-line ART in southern and eastern Africa
      and Latin America, underscoring the need for routine national HIV drug-resistance
      surveillance and review of national policies for first-line ART regimen
      composition. FUNDING: Bill & Melinda Gates Foundation and World Health
      Organization.

PMID- 29198912
TI  - Time to overcome pretreatment HIV drug resistance.

PMID- 29198911
TI  - Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin
      resistance: a prospective multicentre diagnostic accuracy study.
AB  - BACKGROUND: The Xpert MTB/RIF assay is an automated molecular test that has
      improved the detection of tuberculosis and rifampicin resistance, but its
      sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert
      MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We
      compared the diagnostic performance of Xpert Ultra with that of Xpert for
      detection of tuberculosis and rifampicin resistance. METHODS: In this
      prospective, multicentre, diagnostic accuracy study, we recruited adults with
      pulmonary tuberculosis symptoms presenting at primary health-care centres and
      hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia,
      Belarus, and Brazil). Participants were allocated to the case detection group if
      no drugs had been taken for tuberculosis in the past 6 months or to the multidrug
      resistance risk group if drugs for tuberculosis had been taken in the past 6
      months, but drug resistance was suspected. Demographic information, medical
      history, chest imaging results, and HIV test results were recorded at enrolment,
      and each participant gave at least three sputum specimen on 2 separate days.
      Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was
      compared with culture tests and drug susceptibility testing as reference
      standards. The primary objectives were to estimate and compare the sensitivity of
      Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis
      and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert
      specificities for detection of rifampicin resistance. Study participants in the
      case detection group were included in all analyses, whereas participants in the
      multidrug-resistance risk group were only included in analyses of rifampicin
      resistance detection. FINDINGS: Between Feb 18, and Dec 24, 2016, we enrolled
      2368 participants for sputum sampling. 248 participants were excluded from the
      analysis, and 1753 participants were distributed to the case detection group
      (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert
      Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with
      smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24);
      90% and 77%, respectively, for the 115 HIV-positive participants with culture
      positive sputum (13%, 6.4 to 21); and 88% and 83%, respectively, across all 462
      participants with culture-positive sputum (5.4%, 3.3 to 8.0). Specificities of
      Xpert Ultra and Xpert for case detection were 96% and 98% (-2.7%, -3.9 to -1.7)
      overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra
      and Xpert performed similarly in detecting rifampicin resistance. INTERPRETATION:
      For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that
      of Xpert in patients with paucibacillary disease and in patients with HIV.
      However, this increase in sensitivity came at the expense of a decrease in
      specificity. FUNDING: Government of Netherlands, Government of Australia, Bill &
      Melinda Gates Foundation, Government of the UK, and the National Institute of
      Allergy and Infectious Diseases.

PMID- 29198915
TI  - HPV vaccination strategies targeting hard-to-reach populations: Out-of-school
      girls in LMICs.

PMID- 29198914
TI  - Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined
      Subpopulation of Glioblastoma.
AB  - While molecular subtypes of glioblastoma (GBM) are defined using gene expression
      and mutation profiles, we identify a unique subpopulation based on addiction to
      the high-affinity glucose transporter, Glut3. Although Glut3 is a known driver of
      a cancer stem cell phenotype, direct targeting is complicated by its expression
      in neurons. Using established GBM lines and patient-derived stem cells, we
      identify a subset of tumors within the "proneural" and "classical" subtypes that
      are addicted to aberrant signaling from integrin alphavbeta3, which activates a
      PAK4-YAP/TAZ signaling axis to enhance Glut3 expression. This defined
      subpopulation of GBM is highly sensitive to agents that disrupt this pathway,
      including the integrin antagonist cilengitide, providing a targeted therapeutic
      strategy for this unique subset of GBM tumors.

PMID- 29198913
TI  - Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid
      Recruitment.
AB  - Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as
      myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T
      cell responses. Here, we examined the therapeutic potential of combining a direct
      tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs.
      Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple
      lymphoma models, including huCD27 transgenic mice using the anti-huCD27,
      varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing
      demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release
      myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration
      and macrophage activation. This study demonstrates the therapeutic advantage of
      using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and
      activate myeloid cells for enhanced killing of mAb-opsonized tumors.

PMID- 29198916
TI  - Anxiety-related adverse events following immunization (AEFI): A systematic review
      of published clusters of illness.
AB  - BACKGROUND: Clusters of anxiety-related adverse events following immunization
      (AEFI) have been observed in several countries and have disrupted country
      immunization programs. We conducted a systematic literature review to
      characterize these clusters, to generate prevention and management guidance for
      countries. METHODS: We searched seven peer-reviewed databases for English
      language reports of anxiety-related AEFI clusters (>=2 persons) with pre
      specified keywords across 4 categories: symptom term, cluster term, vaccine term,
      and cluster AEFI phenomenon term/phrase. All relevant reports were included
      regardless of publication date, case-patient age, or vaccine. Two investigators
      independently reviewed abstracts and identified articles for full review. Data on
      epidemiologic/clinical information were extracted from full text review including
      setting, vaccine implicated, predominant case-patient symptoms, clinical
      management, community and media response, and outcome/impact on the vaccination
      program. RESULTS: Of 1472 abstracts reviewed, we identified eight published
      clusters, from all six World Health Organization (WHO) regions except the African
      Region. Seven clusters occurred among children in school settings, and one was
      among adult military reservists. The size and nature of these clusters ranged
      from 7 patients in one school to 806 patients in multiple schools. Patients'
      symptoms included dizziness, headache, and fainting with rapid onset after
      vaccination. Implicated vaccines included tetanus (2), tetanus-diphtheria (1),
      hepatitis B (1), oral cholera (1), human papillomavirus (1), and influenza A
      (H1N1)pdm09 (2). In each report, all affected individuals recovered rapidly;
      however, vaccination program disruption was noted in some instances, sometimes
      for up to one year. CONCLUSIONS: Anxiety-related AEFI clusters can be disruptive
      to vaccination programs, reducing public trust in immunizations and impacting
      vaccination coverage; response efforts to restore public confidence can be
      resource intensive. Health care providers should have training on recognition and
      clinical management of anxiety-related AEFI; public health authorities should
      have plans to prevent and effectively manage anxiety-related AEFI clusters.
      Prompt management of these occurrences can be even more important in an era of
      social media, in which information is rapidly spread.

PMID- 29198917
TI  - Early impact of universal varicella vaccination on childhood varicella and herpes
      zoster hospitalizations in Brazil.
AB  - INTRODUCTION: The Brazilian childhood National Immunization Program (NIP)
      introduced live and attenuated varicella vaccination in a single dose, combined
      as tetraviral vaccine, at 15 months of age in the whole country, during September
      to December of 2013. The aim of this study was to report trends in incidence of
      childhood hospital admissions related to varicella and zoster in Brazil from 2003
      to 2016, including the first three years after vaccine introduction. METHODS: The
      number and incidence of hospital admission in patients aged less than 20 years in
      Brazilian public health system with an admission diagnosis of varicella and
      zoster from 2003 to 2016 were analyzed and pre (2003-2013) and post-vaccination
      periods (2014-2016) were compared. The data were obtained from DATASUS, a
      Brazilian government's open-access public health database system, and analyzed
      adjusting for secular trend and seasonality if a statistically significant change
      was found. RESULTS: During the study period, 69,791 admissions due to varicella
      and herpes zoster occurred in the children younger than 20 years. After adjusting
      for seasonality, the incidence of hospitalizations decreased from 27.33 to 14.33
      per 100000 per year, which corresponds to a reduction of 47.6% (95% confidence
      interval 18.19-77.04%, p < 0.001) in the vaccinated age group (1-4 years) in 2014
      2016 compared to pre-vaccination period. The changes were not significant in the
      unvaccinated age groups. CONCLUSION: The hospitalizations due to varicella and
      herpes zoster were decreased by half early after the introduction of a single
      dose of tetraviral vaccine in NIP in the vaccinated children. Further studies may
      assess duration and intensity of this effect, as well as the indirect effect in
      the unvaccinated age groups.

PMID- 29198918
TI  - Observations on the epidemiology of rotavirus infection among hospitalized
      children younger than 5 years in 2 Ukrainian hospitals, 2007-2015.
AB  - BACKGROUND: Acute gastroenteritis remains a burden among children under 5 years
      of age. Ukraine joined the World Health Organization's Global Rotavirus
      Surveillance Network in 2006, with a goal of providing accurate rotavirus burden
      data to aid policy makers in planning for rotavirus vaccine introduction. This
      analysis describes rotavirus epidemiology among Ukrainian children enrolled in
      Kyiv and Odesa, two large Ukrainian cities. METHODS: Children 0-59 months of age
      hospitalized for acute gastroenteritis at 2 sentinel sites in Kyiv and Odesa were
      enrolled into the active, prospective surveillance program. In Odesa, the
      surveillance period was during 2007-2015 and in Kyiv, it was during 2011-2015.
      Acute gastroenteritis was defined as 3 or more episodes of diarrhea per day
      during a 24 h period, with symptom duration before hospitalization not exceeding
      7 days. Guardians of enrolled children completed a questionnaire including
      demographic, clinical and treatment information. Each child provided a stool
      specimen within 2 days of hospitalization. Stools were tested for rotavirus using
      ProSpecTTM Rotavirus Kit (Oxoid Ltd., Great Britain), and positive specimens were
      genotyped. Descriptive data are reported, as well as comparison of demographic,
      clinical and treatment data among rotavirus positive and negative children.
      RESULTS: During July 2007-June 2015, 12,350 children were enrolled in the
      surveillance programs and had stool specimens collected and tested for rotavirus.
      Overall, rotavirus infection was diagnosed in 5412/12350 (44%) of children,
      929/1734 (54%) of those in Kyiv and 4483/10616 (42%) in Odesa. Rotavirus
      infections peaked during the winter months. Children with rotavirus acute
      gastroenteritis displayed more severe clinical symptoms than those without
      rotavirus. Predominant genotypes identified included G1P[8], G2P[4], G3 P[8], G4
      P[8] and G9 P[8]. CONCLUSION: Active surveillance of acute gastroenteritis in
      hospitalized children younger 5 years in two large Ukrainian cities reveals a
      significant burden of rotavirus infection. These data provide scientific
      justification for incorporating rotavirus vaccines into the Ukrainian national
      immunization schedule.

PMID- 29198919
TI  - Does colchicine decrease the rate of recurrence of acute idiopathic pericarditis
      treated with glucocorticoids?
AB  - BACKGROUND: The traditional treatment of acute pericarditis includes non
      steroidal anti-inflammatory agents (NSAIDs) or glucocorticoids. The addition of
      colchicine has been found to reduce the rate of recurrences. Glucocorticoids,
      however, may attenuate this effect, although the available data are limited. We
      examined the impact of colchicine on the rate of recurrence of acute idiopathic
      pericarditis pretreated with prednisone. METHODS: The frequency of recurrence in
      patients hospitalized for acute idiopathic pericarditis in a tertiary medical
      center in 2004-2014 who were treated with glucocorticoids or with non-steroidal
      therapy was assessed from the computerized hospital database. A retrospective
      design was used. RESULTS: The cohort included 199 patients aged 18-86 years.
      Sixty-two (31%) were treated with prednisone, 42 with colchicine and 20 without,
      and 133 with non-steroidal therapy; in 4 patients, therapy was not detailed.
      Follow-up ranged from 13 to 147 months (median, 48 months). Fifty-three patients
      (26.6%) experienced at least one recurrence of pericarditis. The recurrence rate
      was significantly higher in patients who received prednisone and colchicine
      (17/42, 40.5%) than in patients who received NSAIDs or aspirin and colchicine
      (8/44, 18.2%, p=0.03) or any non-steroidal therapy (30/133, 22.6%, p=0.03). There
      was no difference between the rate of recurrence in patients who were treated
      with prednisone alone (5/20, 25%) and those treated with NSAIDs or aspirin and
      colchicine or with any non-steroidal therapy (p=NS). Baseline characteristics and
      duration of follow-up were similar in patients with and without recurrence.
      Hospital stay was longer in patients treated with prednisone alone as compared to
      patients treated with prednisone and colchicine. There were no other differences
      in baseline characteristics between these groups. CONCLUSIONS: The addition of
      colchicine to prednisone in patients admitted for acute idiopathic pericarditis
      does not reduce the risk of recurrence. This finding suggests that prednisone
      blunts the salutary effects of colchicine.

PMID- 29198920
TI  - Impact of post-dilatation on longitudinal stent elongation: An in vitro study.
AB  - OBJECTIVES: To evaluate whether balloon inflation for post-dilatation causes
      longitudinal stent deformation (LSD). METHODS AND RESULTS: Two stents, sized
      2.5mm*28mm and 3.5mm*28mm (Nobori(r), biodegradable polymer biolimus-eluting
      stent; Ultimaster(r), biodegradable polymer sirolimus-eluting stent; Terumo Co.,
      Tokyo, Japan), were deployed at nominal pressure in straight and tapered silicon
      vessel models. Then, post-dilatation was performed in two ways: dilatation from
      the distal (D-P group) or proximal (P-D group) side of the stent. Microscopic
      findings showed that the stents were elongated during every step of the procedure
      regardless of the post-dilatation method and type of vessel model. The D-P group
      showed linear elongation during each step of post-dilatation (straight model:
      28.7+/-0.3mm vs. 29.9+/-0.3mm, p=0.002; tapered model: 28.0+/-0.1mm vs. 29.9+/
      0.1mm, p<0.001). In contrast, in the P-D group, the most significant change was
      observed in the first step of post-dilatation and only slight changes were
      observed thereafter (straight model: 28.6+/-0.1mm vs. 29.5+/-0.1mm, p<0.001;
      tapered model: 28.2+/-0.1mm vs. 29.5+/-0.1mm, p<0.001). Optical frequency domain
      imaging analysis showed that the frequency of stent strut malapposition was
      positively correlated with the percentage change in stent length (r=0.74,
      p<0.0001). CONCLUSION: LSD was observed during every step of post-dilatation in
      both the straight and tapered vessel models. However, some differences were
      observed between the D-P and P-D groups. Minimizing stent strut malapposition may
      reduce the risk of LSD.

PMID- 29198921
TI  - Research progress of capsaicin responses to various pharmacological challenges.
AB  - Capsaicin, a well known vanilloid, has shown evidence of an ample variety of
      biological effects which make it the target of extensive research ever since its
      identification. In spite of the fact that capsaicin causes health hazards in
      quite a few ways, yet, the verity cannot be ignored that capsaicin has several
      therapeutic implications. In patients with hypersensitive bladders, vesical
      instillation of 1 mM capsaicin markedly improved urinary frequency and urge
      incontinence. Again, administration of capsaicin favors an augmentation in lipid
      mobilization and a decrease in adipose tissue mass. Topical capsaicin cream as
      well decreases postsurgical neuropathic pain and is preferred by patients over a
      placebo among other therapies. Several in vitro studies have revealed that
      capsaicin results in growth arrest in some transformed cell lines. Furthermore,
      capsaicin has been proven to be an undeniably exciting molecule and remains a
      valuable drug for alleviating pain and itch. It has been recognized that
      capsaicinoids are the most potential agonists of capsaicin receptor (TRPV1).
      However, vanilloids could exert the beneficial effects not only through the
      receptor-dependent pathway but also through the receptor-independent one. The
      involvement of serotonin, neuropeptide Substance P and somatostatin in the
      pharmacological actions of capsaicin has been expansively investigated. Better
      understanding of the established TRPV1 receptor mechanism as well as exploring
      other possible receptor mechanism may publicize other new clinical efficacies of
      capsaicin. Further, clinical studies are required in several of these conditions
      to establish the efficacy of capsaicin.

PMID- 29198922
TI  - Suppression of miR-127 protects PC-12 cells from LPS-induced inflammatory injury
      by downregulation of PDCD4.
AB  - Spinal cord injury (SCI) is one of the most debilitating injuries. Inflammatory
      response plays a central role in regulating the pathogenesis of acute and chronic
      SCI. Our study explores the role of miR-127 in inflammatory injury induced by
      LPS. PC-12 cells were treated with LPS to induce inflammatory injury. The
      expression of miR-127 and PDCD4 was altered by transient transfection. Cell
      viability was measured using CCK-8 assay and apoptosis using flow cytometry. The
      expression of miR-127 was measured by qRT-PCR. The concentrations of TNF-alpha
      and IL-6 were detected by ELISA. The levels of TLR4, PDCD4, BCL6, core factors of
      JNK and NF-kappaB pathway were assessed by RT-PCR/western blot. Dual luciferase
      reporter assay was conducted to verify the relationship between miR-127 and BCL6.
      LPS induced inflammatory injury in PC-12 cells. LPS also increased the expression
      of miR-127 and PDCD4. miR-127 overexpression promoted the LPS-induced
      inflammatory injury while miR-127 suppression inhibited the injury. BCL6 was a
      target of miR-127 in PC-12 cells. In addition, miR-127 positively regulated PDCD4
      expression, and PDCD4 showed a similar effect on LPS-induced injury in PC-12
      cells. We also found that miR-127 and PDCD4 enhanced the activation of JNK and NF
      kappaB pathway. Further, the expressions of miR-127 and PDCD4 were both
      upregulated in ASCI rats. Our present study demonstrated that miR-127 inhibition
      might exert a protective role in LPS-injured PC-12 cells through regulation of
      PDCD4 expression and the further downstream signaling pathway.

PMID- 29198923
TI  - Enteromorpha and polysaccharides from enteromorpha ameliorate loperamide-induced
      constipation in mice.
AB  - Slow-transit constipation(STC)is a disease characterized by functional
      gastrointestinal disorder. Common laxatives used in clinical practice against
      constipation such as Senna have side effects. Enteromorpha(EP)is a common marine
      alga, and the polysaccharide extracted from EP has been reported possessing anti
      cancer and anti-inflammation effects. The aim of this study is to investigate the
      effects of EP and Polysaccharides from Enteromorpha (PEP) on loperamide induced
      constipated mice model and illustrating mechanism of action. We investigated the
      effect of EP and PEP on fecal water content, defecation frequency and
      gastrointestinal transit (GI) time of loperamide-induced STC mice. In addition,
      serum Nitric Oxide (NO) content and vasoactive intestinal peptide receptor1
      (VIPR1) as well as serotonin receptor (5-HT4) expression in the distal colon were
      analyzed. Furthermore, we determined the role of EP and PEP on microbiota
      distribution using stool genomic 16S rRNA sequencing. EP and PEP significantly
      enhanced intestinal motility function, and alleviated constipation associated
      intestinal inflammation. Moreover, EP and PEP significantly decreased serum NO
      concentration, down-regulated VIPR1 expression and up-regulated 5-HT4 expression
      in distal colon. Genomic stool DNA MiSeq Sequencing Analysis of microbiota
      community structures and distribution revealed that intestinal microecological
      changes caused by constipation recovered after both EP and PEP treatment. Our
      results indicate that EP and PEP are potent natural products which could be
      suggested in constipation therapy strategies.

PMID- 29198924
TI  - Sinomenine hydrochloride attenuates the proliferation, migration, invasiveness,
      angiogenesis and epithelial-mesenchymal transition of clear-cell renal cell
      carcinoma cells via targeting Smad in vitro.
AB  - New strategies for the treatment of clear-cell renal cell carcinoma (ccRCC) are
      urgently needed. Recently, accumulating evidence has demonstrated that sinomenine
      hydrochloride (SH), extracted from the plant sinomenium acutum, has potent anti
      cancer activity in multiple human malignant solid tumors. However, the underlying
      molecular mechanism by which SH treatment exerts its antagonizing tumorigenic
      effects has not been clearly elucidated. In this study, we showed that SH
      treatment exerted profound effects on cell growth in ccRCC in a dose- and time
      dependent manner in vitro. Furthermore, treatment with SH significantly
      suppressed the migration, invasiveness and angiogenesis of ccRCC cells in vitro.
      Mechanistically, we revealed that SH treatment blocked epithelial-mesenchymal
      transition (EMT) through the downregulation of the expression of the
      transcription factors Snail1 and Twist in ccRCC cells. Additionally, the
      depletion of p-Smad2 and p-Smad3 was required for SH treatment to inhibit EMT
      effectively. Taken together, these findings indicate an anti-cancer role for SH
      in ccRCC cells and reveal a potential molecular mechanism by which Smad / EMT
      axis functions in ccRCC, as its hyperactivation has been associated with cell
      proliferation, migration, invasiveness and angiogenesis in this cancer type.
      These observations suggest that SH can act as an efficacious adjuvant
      chemotherapeutic candidate that targets the Smad/EMT axis in patients with ccRCC.

PMID- 29198925
TI  - Teriparatide promotes healing of critical size femur defect through accelerating
      angiogenesis and degradation of beta-TCP in OVX osteoporotic rat model.
AB  - Accumulating evidence suggests that early angiogenesis has an important effect on
      the healing of injury. Teriparatide (PTH) is extensively applied for its potent
      anabolic activity on bone, while little is known about its angiogenic ability
      which may facilitate new bone formation. In this study, we tested the angiogenic
      ability of PTH and its effect on degradation of beta-tricalcium phosphate (beta
      TCP) in an ovariectomized (OVX) rat distal femoral metaphysis model. After
      successful establishment of the OVX model was confirmed, a critical size defect
      was drilled into each distal femur of the OVX rats. Afterwards all animals were
      randomly divided into three groups: control group, group beta-TCP and group beta
      TCP+PTH, then rats of group beta-TCP+PTH were injected Teriparatide (30 MUg/kg)
      subcutaneous every other day. Four weeks after femur surgery, five specimens from
      each group were used for Microfil perfusion to reveal blood vessels in the bone
      defect. The residual rats were harvested for micro-computed tomography,
      histological analysis and immunochemistry. The results showed Teriparatide
      facilitated neovascularization, degradation of beta-TCP and new bone formation in
      combination with beta-TCP, which may be relevant to neovascularization in an
      early phase.

PMID- 29198927
TI  - Morphologic and immunohistochemical features of pulmonary vasculopathy in end
      stage left ventricular systolic failure.

PMID- 29198926
TI  - Does the application of Ankaferd Blood Stopper rectally have positive effects on
      the healing of colorectal anastomosis and prevention of anastomotic leakage? An
      experimental study.
AB  - The purpose of this experimental study was to evaluate the potential effects on
      the healing of colorectal anastomoses of the rectal administration of Ankaferd
      Blood Stopper (ABS). Thirty Wistar-Albino male rats were randomly separated into
      3 groups. In the sham group, only laparotomy and colonic mobilization was
      performed. In the other 2 groups, colon transection and anastomosis were carried
      out. Saline (2 mL, 0.9% NaCl) was given rectally via a feeding tube for 10 days
      after the surgical procedure in the sham and control groups. In Group 3 (ABS
      group), the rats were treated with rectally administered ABS (2 mL/day) for 10
      days. In all groups, after the measurement of bursting pressures, tissue samples
      were collected for the measurement of tissue hydroxyproline and prolidase levels,
      and for histopathological evaluation on postoperative day 11. The rectal
      administration of ABS showed positive effects on bursting pressures, tissue
      prolidase and hydroxyproline levels, and the histopathological findings of
      colonic anastomosis. The rectal application of ABS had positive effects on the
      healing of colorectal anastomosis. As a natural product, it may be used
      effectively and safely to achieve better healing results after colorectal
      anastomosis.

PMID- 29198928
TI  - Lung autoantibodies: Ready for prime time?
AB  - Despite advances in our understanding of the immunology of lung allograft
      tolerance and a reduction in the rate of acute allograft rejection using
      contemporary immunosuppressive protocols, the rate of chronic lung allograft
      dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high.
      CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened
      survival. The development of a consensus approach to the diagnosis of antibody
      mediated rejection by the International Society for Heart and Lung
      Transplantation has highlighted the need for a uniform approach toward the
      investigation, diagnosis, implications and management of both human leukocyte
      antigen (HLA) and non-HLA-related antibody formation. This Perspective summarizes
      the current information that underpins the way forward in recognizing the
      potential importance of non-HLA-related antibody formation with respect to
      allograft injury and outcomes.

PMID- 29198929
TI  - Racial differences in the development of de-novo donor-specific antibodies and
      treated antibody-mediated rejection after heart transplantation.
AB  - BACKGROUND: Despite improvements in outcomes after heart transplantation, black
      recipients have worse survival compared with non-black recipients. The source of
      such disparate outcomes remains largely unknown. We hypothesize that a propensity
      to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody
      mediated rejection (AMR) may account for racial differences in sub-optimal
      outcomes after heart transplant. In this study we aimed to determine the role of
      dnDSA and AMR in racial disparities in post-transplant outcomes. METHODS: This
      study was a single-center, retrospective analysis of 137 heart transplant
      recipients (81% male, 48% black) discharged from Emory University Hospital.
      Patients were classified as black vs non-black for the purpose of our analysis.
      Kaplan-Meier and Cox regression analyses were used to evaluate the association
      between race and selected outcomes. The primary outcome was the development of
      dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft
      dysfunction or death. RESULTS: After 3.7 years of follow-up, 39 (28.5%) patients
      developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models,
      black race was associated with a higher risk of developing dnDSA (hazard ratio
      [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher
      risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non
      black race. Black race was also associated with a higher risk of all-cause graft
      dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p =
      0.044). However, in a multivariable model incorporating dnDSA, black race was no
      longer a significant risk factor. Only dnDSA development was significantly
      associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to
      12.44, p = 0.001). CONCLUSION: Black transplant recipients are at higher risk for
      the development of dnDSA and treated AMR, which may account for racial
      disparities in outcomes after heart transplantation.

PMID- 29198930
TI  - Induction regimen and survival in simultaneous heart-kidney transplant
      recipients.
AB  - BACKGROUND: Induction therapy in simultaneous heart-kidney transplantation (SHKT)
      is not well studied in the setting of contemporary maintenance immunosuppression
      consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED).
      METHODS: We analyzed the Organ Procurement and Transplant Network registry from
      January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on
      TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into
      3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r
      ATG; n = 204), and interleukin-2 receptor-alpha (n = 187) antagonists. Survival
      rates were estimated using the Kaplan-Meier estimator. Multivariable inverse
      probability weighted Cox proportional hazard regression models were used to
      assess hazard ratios associated with post-transplant mortality as the primary
      outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year
      of follow-up. RESULTS: During the study period, the number of SHKTs increased
      nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r
      ATG compared with no induction or interleukin-2 receptor-alpha induction.
      Compared with the no-induction group, an inverse probability weighted Cox
      proportional hazard model showed no independent association of induction therapy
      with the primary outcome. In sub-group analysis, r-ATG appeared to lower
      mortality in sensitized patients with panel reactive antibody of 10% or higher
      (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). CONCLUSION: r-ATG may
      provide a survival benefit in SHKT, especially in sensitized patients maintained
      on TAC/MPA/PRED at hospital discharge.

PMID- 29198931
TI  - Ultrasound-guided maxillary and inferior alveolar nerve blocks for postoperative
      analgesia in gnathoplasty.

PMID- 29198933
TI  - Dimensionality and Reliability of the Central Sensitization Inventory in a Pooled
      Multicountry Sample.
AB  - : Central sensitization (CS) involves the amplification of neural signaling
      within the central nervous system, which evokes pain hypersensitivity. The
      Central Sensitization Inventory (CSI) assesses 25 overlapping health-related
      symptom dimensions that have been reported to be associated with CS-related
      disorders. Previous studies have reported satisfactory test-retest reliability
      and internal consistency, but factor analyses have exhibited conflicting results
      in different language versions. The purpose of this cross-sectional study was to
      thoroughly examine the dimensionality and reliability of the CSI, with pooled
      data from 1,987 individuals, collected in several countries. The principal
      component analysis suggested that 1 general factor of CS best described the
      structure. A subsequent confirmatory factor analysis revealed that a bifactor
      model, which accounted for the covariance among CSI items, with regard to 1
      general factor and 4 orthogonal factors, fit the CSI structure better than the
      unidimensional and the 4-factor models. Additional analyses indicated substantial
      reliability for the general factor (ie, Cronbach alpha = .92; omega = .95; and
      omega hierarchical = .89). Reliability results for the 4 specific factors were
      considered too low to be used for subscales. The results of this study clearly
      suggest that only total CSI scores should be used and reported. PERSPECTIVE: As
      far as we know, this is the first study that has examined the factor structure
      and reliability of the CSI in a large multicountry sample. The CSI is currently
      considered the leading self-report measure of CS-related symptoms worldwide.

PMID- 29198932
TI  - Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis.
AB  - : Despite wide use in clinical practice, acupuncture remains a controversial
      treatment for chronic pain. Our objective was to update an individual patient
      data meta-analysis to determine the effect size of acupuncture for 4 chronic pain
      conditions. We searched MEDLINE and the Cochrane Central Registry of Controlled
      Trials randomized trials published up until December 31, 2015. We included
      randomized trials of acupuncture needling versus either sham acupuncture or no
      acupuncture control for nonspecific musculoskeletal pain, osteoarthritis, chronic
      headache, or shoulder pain. Trials were only included if allocation concealment
      was unambiguously determined to be adequate. Raw data were obtained from study
      authors and entered into an individual patient data meta-analysis. The main
      outcome measures were pain and function. An additional 13 trials were identified,
      with data received for a total of 20,827 patients from 39 trials. Acupuncture was
      superior to sham as well as no acupuncture control for each pain condition (all P
      < .001) with differences between groups close to .5 SDs compared with no
      acupuncture control and close to .2 SDs compared with sham. We also found clear
      evidence that the effects of acupuncture persist over time with only a small
      decrease, approximately 15%, in treatment effect at 1 year. In secondary
      analyses, we found no obvious association between trial outcome and
      characteristics of acupuncture treatment, but effect sizes of acupuncture were
      associated with the type of control group, with smaller effects sizes for sham
      controlled trials that used a penetrating needle for sham, and for trials that
      had high intensity of intervention in the control arm. We conclude that
      acupuncture is effective for the treatment of chronic pain, with treatment
      effects persisting over time. Although factors in addition to the specific
      effects of needling at correct acupuncture point locations are important
      contributors to the treatment effect, decreases in pain after acupuncture cannot
      be explained solely in terms of placebo effects. Variations in the effect size of
      acupuncture in different trials are driven predominantly by differences in
      treatments received by the control group rather than by differences in the
      characteristics of acupuncture treatment. PERSPECTIVE: Acupuncture is effective
      for the treatment of chronic musculoskeletal, headache, and osteoarthritis pain.
      Treatment effects of acupuncture persist over time and cannot be explained solely
      in terms of placebo effects. Referral for a course of acupuncture treatment is a
      reasonable option for a patient with chronic pain.

PMID- 29198935
TI  - Metacarpophalangeal portal safety. An anatomical study.
AB  - AIM: To quantify the risk of dorsal innervation injury when performing direct
      metacarpophalangeal joint portals of the second to fifth fingers. MATERIAL AND
      METHOD: An anatomical study of 11 upper limbs of fresh corpses was carried out.
      After placing them in a traction tower, the metacarpophalangeal portals were
      developed on both sides of the extensor tendon. The dorsal sensory branches were
      dissected and the distances between the portal and the nearest nerve were
      measured by a digital caliper. The portals of all the fingers were compared
      globally to assess the safest finger and two to two radial and ulnar portals were
      compared in each of the fingers to assess the safest portal within each finger.
      RESULTS: The overall comparison of all portals and fingers showed that the third
      finger is the safest in any of its portals, while the ulnar side of the second
      and radial of the fourth are the portals with the highest risk of nerve injury
      (P=8.96.10-5). Comparing two to two of the radial and ulnar portals in each of
      the fingers showed that the ulnar portal is safer than the radial on the fourth
      finger (P=.042), while the radial is safer than the ulnar on the fifth finger
      (P=.003). CONCLUSIONS: The third finger was the safest to perform
      metacarpophalangeal portals, while the ulnar side of the second finger and radial
      side of the fourth had the highest risk of nerve injury.

PMID- 29198934
TI  - Novel polymorphisms associated with hyperalphalipoproteinemia and apparent
      cardioprotection.
AB  - BACKGROUND: Hyperalphalipoproteinemia (HALP) is inversely correlated with
      coronary heart disease (CHD) although genetic variants associated with high serum
      levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be
      cardioprotective. OBJECTIVE: The objective of the study was to uncover novel
      genetic variants associated with HALP and possibly with reduced risk of CHD.
      METHODS: Exome sequencing data, HDL-C, and triglyceride levels were analyzed in
      1645 subjects. They included the University of Maryland outpatients with high HDL
      C (n = 12), Cardiovascular Health Study (n = 210), Jackson Heart Study (n = 402),
      Multi-Ethnic Study of Atherosclerosis (n = 404), Framingham Heart Study (n =
      463), and Old Order Amish (n = 154). RESULTS: Novel nonsynonymous single
      nucleotide polymorphisms (nsSNPs) were identified in men and women with primary
      HALP (mean HDL-C, 145 +/- 30 mg/dL). Using PolyPhen-2 and Combined Annotation
      Dependent Depletion to estimate the predictive effect of each nsSNP on the gene
      product, rare, deleterious polymorphisms in UGT1A3, PLLP, PLEKHH1, ANK2, DIS3L,
      ACACB, and LRP4 were identified in 16 subjects with HALP but not in any tested
      subject with low HDL-C (<40 mg/dL). In addition, a single novel polymorphism,
      rs376849274, was found in OSBPL1A. The majority of these candidate genes have
      been implicated in fat and lipid metabolism, and none of these subjects has a
      history of CHD despite 75% of subjects having risk factors for CHD. Overall, the
      probability of finding these nsSNPs in a non-high HDL-C population ranges from 1
      * 10-17 to 1 * 10-25. CONCLUSION: Novel functional polymorphisms in 8 candidate
      genes are associated with HALP in the absence of CHD. Future study is required to
      examine the extent to which these genes may affect HDL function and serve as
      potential therapeutic targets for CHD risk reduction.

PMID- 29198936
TI  - Reaching low-density lipoprotein cholesterol treatment targets in stable coronary
      artery disease: Determinants and prognostic impact.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) reduction is an integral
      part of the management of patients with coronary artery disease (CAD). AIMS: To
      assess attainment of LDL-C goals during long-term treatment of patients with
      stable CAD, and to determine predictors of goal attainment and the prognostic
      impact of reaching LDL-C<70mg/dL (1.8mmol/L) in a real-life setting. METHODS:
      Data were obtained for 4080 outpatients with stable CAD included in the
      multicentre CORONOR study. Five-year follow-up was achieved for 3991 (97.8%)
      patients. RESULTS: At inclusion, a recent (<1 year) measurement of LDL-C was
      available in 3757 (92.1%) patients. LDL-C<70mg/dL was reached by 885 (23.6%)
      patients. Independent predictors of LDL-C<70mg/dL were diabetes mellitus, statin
      treatment, treatment with renin-angiotensin system inhibitors, previous
      myocardial infarction and short time since last coronary event. The adjusted
      hazard ratio (HR) for the composite endpoint (cardiovascular death, myocardial
      infarction, ischemic stroke or coronary revascularization) during the 5-year
      follow-up was 1.31 (95% confidence interval [CI]: 1.09-1.58; P=0.004) for LDL
      C>=70mg/dL versus<70mg/dL. When compared with patients with LDL-C<70mg/dL, the
      adjusted HRs for LDL-C 70-99mg/dL and >=100mg/dL (2.6mmol/L) were 1.27 (95% CI:
      1.05-1.55; P=0.016) and 1.38 (95% CI: 1.12-1.70; P=0.003), respectively. When LDL
      C was used as a continuous variable, the adjusted HRs for increases of 10mg/dL
      (0.3mmol/L) and 1mmol/L were 1.05 (95% CI: 1.03-1.08) and 1.21 (95% CI: 1.10
      1.33), respectively. CONCLUSIONS: In this observational study, only a minority of
      stable CAD patients had LDL-C<70mg/dL. The patients who reached their LDL-C goal
      had the lowest risk of cardiovascular events.

PMID- 29198937
TI  - Cardiopulmonary exercise testing in the evaluation of liver disease in adults who
      have had the Fontan operation.
AB  - BACKGROUND: Liver disease (LD) is a long-term complication in patients with a
      single ventricle who have had the Fontan operation. A decline in cardiopulmonary
      exercise testing (CPET) variables is associated with increased risk of
      hospitalization, but its association with LD is unknown. AIM: To determine the
      association between CPET variables and LD in adults who have had the Fontan
      operation. METHODS: We retrospectively reviewed the medical records from two
      tertiary institutions. RESULTS: We identified 114 adults (>=18 years; mean 30.9+/
      7.4 years) who had undergone the Fontan operation: 56% were women; 63% had total
      cavopulmonary connection; 66% had New York Heart Association (NYHA) class I
      status; 42% had arrhythmias; 22% had systemic right ventricle; and 35% had
      ventricular dysfunction. Of 81 patients with liver-imaging data, 41% had LD (i.e.
      imaging evidence of cirrhosis, with or without portal hypertension, splenomegaly
      or varices). There were no differences in clinical or echocardiographic variables
      between those with and without LD. Among the 58 patients with CPET data, mean
      peak oxygen consumption (VO2) was 18.6+/-5.7mL/kg/min, per-cent-predicted peak
      VO2 was 53.9+/-15.5%, peak oxygen pulse was 9.3+/-2.9mL/beat and per-cent
      predicted peak oxygen pulse was 82.6+/-21.5%. Of the 44 patients with liver and
      CPET data, each standard deviation decrease in per-cent-predicted peak VO2 (16%)
      and per-cent-predicted peak oxygen pulse (22%) was associated with a 2.3-fold
      increase in the odds of LD, after adjusting for NYHA, institution and Fontan type
      (P=0.04). Similarly, each standard deviation decrease in per-cent-predicted peak
      VO2 and oxygen pulse was associated with an estimated 5.9-year and 4.9-year
      earlier onset of LD, respectively (P>0.05). CONCLUSIONS: Decline in per-cent
      predicted peak VO2 and oxygen pulse was associated with increased odds of LD in
      adults who had undergone the Fontan operation. Our study supports more rapid
      hepatic evaluation among patients with abnormal or worsening CPET variables.

PMID- 29198938
TI  - Outcomes of arthroscopic revision rotator cuff repair with acellular human dermal
      matrix allograft augmentation.
AB  - BACKGROUND: The purpose was to assess the minimum 2-year patient-reported
      outcomes and failure rate of patients who underwent revision arthroscopic rotator
      cuff repair augmented with acellular human dermal matrix (AHDM) allograft for
      repairable retears. METHODS: From 2008-2014, patients who underwent revision
      rotator cuff repair augmented with AHDM with greater than 2 years' follow-up by a
      single surgeon were retrospectively reviewed. Data regarding surgical history,
      demographic characteristics, and medical comorbidities were collected. Outcome
      data included American Shoulder and Elbow Surgeons (ASES) and Single Assessment
      Numeric Evaluation (SANE) scores, as well as rotator cuff healing on magnetic
      resonance imaging or ultrasound. Retears and subsequent surgical procedures were
      characterized. RESULTS: A total of 28 patients met our inclusion criteria, and 23
      (82%) were available for follow-up at 2 years. The mean age was 60.1 +/- 9.3
      years (range, 43-79 years), with a mean follow-up period of 48 +/- 23 months. All
      patients had at least 1 prior rotator cuff repair. Of the 23 patients, 13 (56%)
      underwent postoperative imaging, and 4 of these 13 (31%) had a retear. A
      reoperation was performed in 3 of 23 patients (13%). Among the 6 patients with
      both preoperative and postoperative outcome scores, we saw improvement in the
      ASES score from 56 to 85 (P = .03) and in the SANE score from 42 to 76 (P = .03).
      The full cohort's mean postoperative ASES and SANE scores were 77 and 69,
      respectively. CONCLUSION: AHDM allograft augmentation is a safe and effective
      treatment method for patients with full-thickness rotator cuff retears. Further
      research is needed with larger studies to confirm these findings from our small
      cohort of patients.

PMID- 29198939
TI  - Three-dimensional computed tomography measurement accuracy of varying Hill-Sachs
      lesion size.
AB  - BACKGROUND: The glenoid track concept has been proposed to correlate shoulder
      stability with bone loss. Accurate assessment of Hill-Sachs lesion size
      preoperatively may affect surgical planning and postoperative outcomes; however,
      no measurement method has been universally accepted. This study aimed to assess
      the accuracy and reliability of measuring Hill-Sachs lesion sizes using 3
      dimensional (3D) computed tomography (CT). METHODS: Nine polyurethane humerus
      bone substitutes were used to create Hill-Sachs lesions of varying sizes with a
      combination of lesion depth (shallow, intermediate, and deep) and width (small,
      medium, and large). Specimens were scanned with a clinical CT scanner for size
      measurements and a micro-CT scanner for measurement of true lesion size. Six
      evaluators repeated measurements twice in a 2-week interval. Scans were measured
      by use of 3D CT reconstructions for length, width, and Hill-Sachs interval and
      with use of 2D CT for depth. The interclass correlation coefficient evaluated
      interobserver and intraobserver variability and percentage error, and Student t
      tests assessed measurement accuracy. RESULTS: Interclass correlation coefficient
      reliability demonstrated strong agreement for all variables measured (0.856
      0.975). Percentage error between measured length and measured depth and the true
      measurement significantly varied with respect to both lesion depth (P = .003 and
      P = .005, respectively) and lesion size (P = .049 and P = .004, respectively).
      DISCUSSION AND CONCLUSIONS: The 3D CT imaging is effective and reproducible in
      determining lesion size. Determination of Hill-Sachs interval width is also
      reliable when it is applied to the glenoid track concept. Measured values on 3D
      and 2-dimensional imaging using a conventional CT scanner may slightly
      underestimate true measurements.

PMID- 29198940
TI  - Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a
      Histamine-Dependent Feedback Loop.
AB  - Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery
      from injury, but little is known about how they are regulated within the bone
      marrow niche. Here we describe an auto-/paracrine physiologic circuit that
      controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine
      decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical
      proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB
      HSCs to promote their quiescence and self-renewal. Depleting histamine-producing
      cells enforces cell cycle entry, induces loss of serial transplant capacity, and
      sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid
      cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and
      progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence
      in the absence of histamine feedback, leading to their depletion, while an H2
      agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples
      lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce
      homeostasis.

PMID- 29198941
TI  - Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem
      like Cells.
AB  - Tumor hypoxia is associated with poor patient survival and is a characteristic of
      glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells
      (GSCs) within the hypoxic niche, although the molecular mechanisms linking
      hypoxia to Notch activation have not been clearly delineated. Here we show that
      Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin
      is preferentially induced in GSCs by a HIF1alpha/STAT3 co-activator complex and
      stabilizes Notch1 protein at the cell membrane. This interaction prevents Numb
      from binding Notch1, rescuing it from Numb-mediated lysosomal degradation. Thus,
      Vasorin acts as a switch to augment Notch signaling under hypoxic conditions.
      Vasorin promotes tumor growth and reduces survival in mouse models of
      glioblastoma, and its expression correlates with increased aggression of human
      gliomas. These findings provide mechanistic insights into how hypoxia promotes
      Notch signaling in glioma and identify Vasorin as a potential therapeutic target.

PMID- 29198942
TI  - Dye-Independent Methods Reveal Elevated Mitochondrial Mass in Hematopoietic Stem
      Cells.
AB  - Hematopoietic stem cells (HSCs) produce most cellular energy through glycolysis
      rather than through mitochondrial respiration. Consistent with this notion,
      mitochondrial mass has been reported to be low in HSCs. However, we found that
      staining with MitoTracker Green, a commonly used dye to measure mitochondrial
      content, leads to artefactually low fluorescence specifically in HSCs because of
      dye efflux. Using mtDNA quantification, enumeration of mitochondrial nucleoids,
      and fluorescence intensity of a genetically encoded mitochondrial reporter, we
      unequivocally show here that HSCs and multipotential progenitors (MPPs) have
      higher mitochondrial mass than lineage-committed progenitors and mature cells.
      Despite similar mitochondrial mass, respiratory capacity of MPPs exceeds that of
      HSCs. Furthermore, although elevated mitophagy has been invoked to explain low
      mitochondrial mass in HSCs, we observed that mitochondrial turnover capacity is
      comparatively low in HSCs. We propose that the role of mitochondria in HSC
      biology may have to be revisited in light of these findings.

PMID- 29198944
TI  - The Study of Clear Cell Renal Cell Carcinoma with MR Diffusion Kurtosis Tensor
      Imaging and Its Histopathologic Correlation.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to compare the
      performance of diffusion kurtosis tensor imaging and diffusion-weighted imaging
      in the characterization of clear cell renal cell carcinoma (ccRCC) and their
      correlations with tumor histopathology. MATERIALS AND METHODS: Ninety-one
      patients diagnosed with ccRCC who underwent diffusion kurtosis tensor imaging
      were included in this study. Fractional anisotropy, mean diffusivity, radial
      diffusivity, axial diffusivity, mean kurtosis (MK), radial kurtosis (Krad), and
      axial kurtosis (Kax) data were produced. A nuclear grade of 1-4 (G1-4) was
      assigned for each case based on the Fuhrman grading system, whereas tumor
      histopathology was characterized by the nuclear-to-cytoplasm ratio, the cell
      nuclei count, and the cell volume fraction. RESULTS: All of the metric values
      except for Kax and fractional anisotropy could be used to discriminate G1 vs G3,
      G1 vs G4, G2 vs G3, and G2 vs G4, whereas MK and Kax could be used to
      discriminate G3 vs G4 (P <0.05). Moreover, the MK and Krad values exhibited
      better performance in differentiating G2 from G3 (P < 0.04 compared to the other
      metrics). The nuclear-to-cytoplasm ratio was positively correlated with the MK,
      Krad, and Kax values (P <0.001) and negatively correlated with the mean
      diffusivity, radial diffusivity, and axial diffusivity values (P <0.001), whereas
      the cell volume fraction and the cell nuclei count did not correlate with any
      metric examined. CONCLUSION: The kurtosis metrics were superior to the diffusion
      metrics in grading ccRCC.

PMID- 29198945
TI  - Quantitative Measurements Versus Receiver Operating Characteristics and Visual
      Grading Regression in CT Images Reconstructed with Iterative Reconstruction: A
      Phantom Study.
AB  - RATIONALE AND OBJECTIVES: This study aimed to evaluate the correlation of
      quantitative measurements with visual grading regression (VGR) and receiver
      operating characteristics (ROC) analysis in computed tomography (CT) images
      reconstructed with iterative reconstruction. MATERIALS AND METHODS: CT scans on a
      liver phantom were performed on CT scanners from GE, Philips, and Toshiba at
      three dose levels. Images were reconstructed with filtered back projection (FBP)
      and hybrid iterative techniques (ASiR, iDose, and AIDR 3D of different
      strengths). Images were visually assessed by five readers using a four- and five
      grade ordinal scale for liver low contrast lesions and for 10 image quality
      criteria. The results were analyzed with ROC and VGR. Standard deviation, signal
      to-noise ratios, and contrast-to-noise ratios were measured in the images.
      RESULTS: All data were compared to FBP. The results of the quantitative
      measurements were improved for all algorithms. ROC analysis showed improved
      lesion detection with ASiR and AIDR and decreased lesion detection with iDose.
      VGR found improved noise properties for all algorithms, increased sharpness with
      iDose and AIDR, and decreased artifacts from the spine with AIDR, whereas iDose
      increased the artifacts from the spine. The contrast in the spine decreased with
      ASiR and iDose. CONCLUSIONS: Improved quantitative measurements in images
      reconstructed with iterative reconstruction compared to FBP are not equivalent to
      improved diagnostic image accuracy.

PMID- 29198943
TI  - Human bile acid transporter ASBT (SLC10A2) forms functional non-covalent
      homodimers and higher order oligomers.
AB  - The human apical sodium-dependent bile acid transporter, hASBT/SLC10A2, plays a
      central role in cholesterol homeostasis via the efficient reabsorption of bile
      acids from the distal ileum. hASBT has been shown to self-associate in higher
      order complexes, but while the functional role of endogenous cysteines has been
      reported, their implication in the oligomerization of hASBT remains unresolved.
      Here, we determined the self-association architecture of hASBT by site-directed
      mutagenesis combined with biochemical, immunological and functional approaches.
      We generated a cysteine-less form of hASBT by creating point mutations at all 13
      endogenous cysteines in a stepwise manner. Although Cysless hASBT had
      significantly reduced function correlated with lowered surface expression, it
      featured an extra glycosylation site that facilitated its differentiation from wt
      hASBT on immunoblots. Decreased protein expression was associated with
      instability and subsequent proteasome-dependent degradation of Cysless hASBT
      protein. Chemical cross-linking of wild-type and Cysless species revealed that
      hASBT exists as an active dimer and/or higher order oligomer with apparently no
      requirement for endogenous cysteine residues. This was further corroborated by co
      immunoprecipitation of differentially tagged (HA-, Flag-) wild-type and Cysless
      hASBT. Finally, Cysless hASBT exhibited a dominant-negative effect when co
      expressed with wild-type hASBT which validated heterodimerization/oligomerization
      at the functional level. Combined, our data conclusively demonstrate the
      functional existence of hASBT dimers and higher order oligomers irrespective of
      cysteine-mediated covalent bonds, thereby providing greater understanding of its
      topological assembly at the membrane surface.

PMID- 29198946
TI  - Prognostic Factors for Survival After Transarterial Chemoembolization Combined
      with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas.
AB  - RATIONALE AND OBJECTIVE: The objective of this study was to analyze prognostic
      factors for survival after transarterial chemoembolization (TACE) combined with
      sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer
      (BCLC) stages B and C. MATERIALS AND METHODS: Clinical data of 198 patients with
      BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June
      2012 and January 2017 were retrospectively collected and analyzed. Survival
      curves were detected using log-rank test. Univariate analysis was performed using
      log-rank test with respect to 11 prognostic factors potentially affecting
      survival. All statistically significant prognostic factors identified by
      univariate analysis were entered into a Cox proportion hazards regression model
      to identify independent predictors of survival. P values were two-sided and P <
      0.05 was considered statistically significant. RESULTS: By the end of this study,
      the median follow-up duration was 43.6 months. The median overall survival (OS)
      of the patients was 21.0 months (95% confidence interval [CI]: 16.94-25.05), and
      the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively.
      Tumor size (chi2 = 33.607, P < 0.0001), tumor number (chi2 = 4.084, P = 0.043),
      Child-Pugh class (chi2 = 33.187, P < 0.0001), BCLC stage (chi2 = 50.224, P <
      0.0001), portal vein tumor thrombus (chi2 = 88.905, P < 0.0001), Eastern
      Cooperative Oncology Group (ECOG) performance status (chi2 = 98.007, P < 0.0001),
      extrahepatic spread (chi2 = 34.980, P < 0.0001), TACE times (chi2 = 8.350, P =
      0.015), and sorafenib treatment strategy (chi2 = 81.593, P < 0.0001) were found
      to be significantly associated with OS by univariate analysis. Multivariate
      analysis showed that BCLC stage (95% CI: 1.133-3.982, P = 0.019), extrahepatic
      spread (95% CI: 1.136-2.774, P = 0.012), and sorafenib treatment duration (95%
      CI: 0.352-0.574, P = 0.000) were independent prognostic factors associated with
      OS. There were no serious treatment-related adverse events. CONCLUSIONS: This
      study showed that extrahepatic spread was a risk factor, and sorafenib treatment
      and superior BCLC stage were protective factors. Therefore, the study indicated
      that TACE combined with sorafenib was an effective and safe treatment for
      patients with BCLC stage B HCC without extrahepatic spread.

PMID- 29198947
TI  - Determinants of Difficulty and Discriminating Power of Image-based Test Items in
      Postgraduate Radiological Examinations.
AB  - RATIONALE AND OBJECTIVES: The psychometric characteristics of image-based test
      items in radiological written examinations are not well known. In this study, we
      explored difficulty and discriminating power of these test items in postgraduate
      radiological digital examinations. MATERIALS AND METHODS: We reviewed test items
      of seven Dutch Radiology Progress Tests (DRPTs) that were taken from October 2013
      to April 2017. The DRPT is a semiannual formative examination, required for all
      Dutch radiology residents. We assessed several stimulus and response
      characteristics of test items. The response format of test items included true or
      false, single right multiple choice with 2, 3, 4, or >=5 answer options, pick-N
      multiple-choice, drag-and-drop, and long-list-menu formats. We calculated item P
      values and item-rest-correlation (Rir) values to assess difficulty and
      discriminating power. We performed linear regression analysis in image-based test
      items to investigate whether P and Rir values were significantly related to
      stimulus and response characteristics. Also, we compared psychometric indices
      between image-based test items and text-alone items. RESULTS: P and Rir values of
      image-based items (n = 369) were significantly related to the type of response
      format (P < .001), and not to which of the seven DRPTs the item was obtained
      from, radiological subspecialty domain, nonvolumetric or volumetric character of
      images, or context-rich or context-free character of the stimulus. When accounted
      for type of response format, difficulty and discriminating power of image-based
      items did not differ significantly from text-alone items (n = 881). Test items
      with a relatively large number of answer options were generally more difficult,
      and discriminated better among high- and low-performing candidates. CONCLUSION:
      In postgraduate radiological written examinations, difficulty and discriminating
      power of image-based test items are related to the type of response format and
      are comparable to those of text-alone items. We recommend a response format with
      a relatively large number of answer options to optimize psychometric indices of
      radiological image-based test items.

PMID- 29198949
TI  - Prediabetes Is Associated with Unfavorable Outcome in Young Adult Patients with
      Ischemic Stroke: Methodological Issues.

PMID- 29198948
TI  - Multivariate Prognostic Model of Acute Stroke Combining Admission Infarct
      Location and Symptom Severity: A Proof-of-Concept Study.
AB  - BACKGROUND: The information on topographic distribution of acute ischemic infarct
      can contribute to prediction of functional outcome. We aimed to develop a
      multivariate model for stroke prognostication, combining admission clinical and
      imaging variables, including the infarct topology. METHODS: Acute ischemic stroke
      patients without baseline functional disability who had magnetic resonance
      imaging within 24 hours of onset or last-seen-well were included. The admission
      stroke severity was determined using the National Institutes of Health Stroke
      Scale (NIHSS) score. The relation between infarct location and outcome was
      assessed using both voxel-based and visual atlas-based analyses. The
      disability/death was defined by a modified Rankin Scale score greater than 2 at 3
      month follow-up. RESULTS: Among 198 patients included in this study, higher
      admission NIHSS score (P < .001), larger infarct volume (P < .001), and major
      arterial occlusions (P < .001) were associated with disability/death in
      univariate analyses. On voxel-based analysis, infarcts in the middle centrum
      semiovale, insula, and midbrain/pons were associated with higher rates of
      disability/death. In multivariate analysis, admission NIHSS score (P < .001),
      infarction of insula (P = .005), and midbrain/pons (P = .006) were independent
      predictors of disability/death. In receiver operating characteristics analysis, a
      simple 0-to-3 scoring system using these 3 variables had an area under the curve
      of .812 for prediction of disability/death (P < .001). CONCLUSIONS: Admission
      symptom severity, infarction of insula, and midbrain/pons were independent
      predictors of clinical outcome in acute ischemic stroke patients. The methodology
      of this hypothesis-generating study can help conceive quantitative population
      based probabilistic models for prognostication or treatment triage in stroke
      patients, combining admission clinical and imaging findings-including infarct
      topography.

PMID- 29198950
TI  - Comparison among ultrasonic, electrical apparatus, and toxic chemicals for
      vestibular lesion in mice.
AB  - BACKGROUND: The vestibular lesion (VL) is required to examine the physiological
      function of the vestibular system in animals. Toxic chemicals or electrical
      apparatus have been used for the VL, however, they are not ideal as they have low
      specificity, and can result in unintended damage, and systemic toxic effect. NEW
      METHOD: Localized vibration-induced VL, using an ultrasonicator, is expected to
      overcome the problems associated with chemical and electrical lesions. Thus, we
      examined the effect of the ultrasonication on the VL from the aspects of both the
      physiological function and histology in the present study. RESULTS: and
      Comparison with Existing Method(s) Complete VL, which was evaluated by
      deterioration of swimming skills, righting reflex, and body stability, was
      induced using an ultrasonicator or electrical apparatus. Histological evaluation
      shows that hair cell layers in the saccule and utricle were completely destroyed
      in both methods Furthermore, significant drop in body mass was observed in VL.
      However, abscess at the cranial base was observed in VL induced by the electrical
      apparatus in ICR mice. Complete chemically-induced VL was observed in C57BL/6J
      but not ICR mice, and systemic leakage of the toxic chemicals (arsenic) was not
      detectable even 1day after surgery. CONCLUSIONS: Compared to the electrical
      apparatus, the ultrasonicator is useful for inducing VL in ICR and C57BL/6J mice,
      as it results in less non-specific damage. Toxic chemicals can be used for
      inducing VL in C57BL/6J mice; however, this method does not ensure complete
      disruption of the hair cells in the saccule and utricle.

PMID- 29198951
TI  - Prospective evaluation of chronic pain disorders and treatments.
AB  - BACKGROUND: The incidence of chronic pain is variable among individuals who have
      sustained traumatic or surgical injury. Also, treatments for pain rarely are
      effective consistently for a procedure or agent, and no therapies are considered
      effective for pain that is chronic. NEW METHOD: Difficulties with standard
      methods for conducting clinical trials call attention to a need for protocols
      that provide a new understanding of the development of and control over chronic
      pain. Prospective single-subject research designs can document varieties of pain
      progression over time for individuals. Subsequent grouping of individuals with
      common characteristics directs a mechanism-based approach to therapy. RESULTS:
      Tracking of individuals' pain and associated influences over time is consistent
      with clinical practice, noting and adapting to changes that occur. COMPARISON
      WITH EXISTING METHODS: Grouping patients with diverse characteristics and
      variable effects of therapy is problematic. Conventional evaluation of pain
      assesses patients with similar injuries or surgery without characterizations of
      individuals who develop chronic pain or recover over time. Also, classical
      evaluation of therapies involves comparison of groups receiving treatment or a
      placebo without characterization of patients with successful and unsuccessful
      results. CONCLUSIONS: Single-subject prospective studies can inform clinical
      trials according to individual differences that would be obscured by comparison
      of groups with unknown variation in characteristics that influence pain and
      therapeutic effectiveness.

PMID- 29198952
TI  - Update on fosfomycin-modified genes in Enterobacteriaceae.
AB  - The long-used antibiotic fosfomycin has recently been re-evaluated as a potential
      regimen for treating extended-spectrum beta-lactamases (ESBLs) and carbapenem
      resistant Enterobacteriaceae (CRE). Fosfomycin is known for its robust
      bactericidal effect against ESBL-producing Enterobacteriaceae and CRE. However,
      fosfomycin-modified genes have been reported in transposon elements and
      conjugative plasmids, resulting in fosfomycin resistance in parts of East Asia.
      Here we review reports of fosfomycin-modified (fos) genes in Enterobacteriaceae
      and assess the efficacy of fosfomycin against multidrug-resistant
      Enterobacteriaceae infections. At least 10 kinds of fos genes have been
      identified in the past decade; of these, fosA (and fosA subtypes) and fosC2 are
      primarily found in Enterobacteriaceae. All fosA subtypes except fosA2 are found
      in plasmids and transposons, nearby insertion sequence elements, or integrons,
      indicating that mobilizing elements also play an important role in plasmid
      mediated fos genes in Enterobacteriaceae. fosA3, which is prevalent in East Asia,
      has been transmitted (mostly by animals) within and across continents via IS26
      mobile elements. The acquisition of multiple antibiotic resistance genes via
      plasmids and mobile elements has resulted in a need for combined treatments for
      Enterobacteriaceae cases. The combination of fosfomycin and carbapenem has been
      the focus of many in vitro studies, but there is a clear need for additional in
      vivo investigations involving pharmacokinetics.

PMID- 29198953
TI  - National bundle care program implementation to reduce ventilator-associated
      pneumonia in intensive care units in Taiwan.
AB  - BACKGROUND/PURPOSE: This study investigated the impact of implementing ventilator
      associated pneumonia (VAP) bundle care on the rates of VAP in intensive care
      units (ICUs) in Taiwan. METHODS: A total of 10 ICUs (bed number, 170), including
      surgical (SICUs) (n = 7), cardiovascular/surgical (CV/S-ICUs) (n = 1), and
      medical ICUs (MICUs) (n = 2) from 10 hospitals (7 medical center hospitals and 3
      regional hospitals) were enrolled in this quality-improvement project. This study
      was divided into the pre-intervention phase (1st January, 2012-31st July, 2013)
      and the intervention phase (1st August, 2013-31st October, 2014). RESULTS: Among
      the 10 hospitals, the overall rates (cases per 1000 ventilator-days) of VAP
      declined significantly (p = 0.005; rate ratio, 0.71) from 1.9 in the pre
      intervention period to 1.5 in the intervention period. Significant difference in
      VAP rates between these periods was found in the regional hospitals (from 1.6 to
      0.7; p < 0.001) and the SICUs (from 2.1 to 1.4; p < 0.001), but not in the
      medical centers (2.0 vs. 1.9; p = 0.0667) or CV/S-ICUs (4.5 vs. 4.5; p = 0.5391).
      However, VAP rate increased significantly (cases per 1000 ventilator-days) in the
      MICUs between the two periods (from 0.5 to 1.0; p = 0.0489). For the VAP bundle
      care elements, the overall compliance rate was 87.7% with 83.6% and 97.9% in the
      medical centers and regional hospitals, respectively. CONCLUSIONS: Implementing
      VAP bundle care has effectively reduced VAP in Taiwanese ICUs, but differences in
      performance and compliance rates of VAP bundle care among the different ICUs and
      hospital categories did exist.

PMID- 29198954
TI  - Metabolic reprogramming of hydrogenosomal amino acids in Trichomonas vaginalis
      under glucose restriction.
AB  - BACKGROUND: Glucose is the major energy source that is converted to pyruvate for
      ATP generation in the trichomonad hydrogenosome. Under glucose restriction (GR),
      the regulation of amino acids metabolism is crucial for trichomonad growth and
      survival. RNA-sequencing (RNA-seq) analysis has been used to identify
      differentially expressed genes in Trichomonas vaginalis under GR, leading to
      significant advances in understanding adaptive responses of amino acid metabolism
      to GR. However, the levels of amino acid metabolites modulated by GR are unknown
      in T. vaginalis. METHODS: Herein, we describe a comprehensive metabolomic
      analysis of amino acid metabolites in the hydrogenosome using liquid
      chromatography Fourier transform ion cyclotron resonance mass spectrometry (LC-FT
      MS). The relative abundance of 17 hydrogenosomal amino acids was analyzed under
      GR and high-glucose (HG) conditions. RESULTS: Levels of most amino acids were
      higher in GR culture. Arginine was not detectable in either HG or GR cultures;
      however, its metabolic end-product proline was slightly increased under GR,
      suggesting that the arginine dihydrolase pathway was more activated by GR.
      Additionally, methionine catabolism was less stimulated under GR because of
      greater methionine accumulation. Furthermore, branched chain amino acids (BCAA),
      including leucine, isoleucine and valine, as well as phenylalanine and alanine,
      markedly accumulated under GR, indicating that glutamate-related metabolic
      pathways were remarkably enhanced in this setting. Our metabolomic analysis
      combined with previous RNA-seq data confirm the existence of several amino acid
      metabolic pathways in the hydrogenosome and highlight their potentially important
      roles in T. vaginalis under glucose deprivation.

PMID- 29198955
TI  - Sounding the Alarm.

PMID- 29198956
TI  - Effects of staining method and clinician experience on the evaluation of stallion
      sperm morphology.
AB  - Evaluation of sperm morphology is part of the assessment of fertility in human
      and animal reproduction. Analyses can be performed using different techniques,
      including the use of staining methods In our prospective study, the morphology of
      equine sperm was evaluated using 3 staining methods Diff-Quik, eosin-nigrosin,
      and SpermBlue, the latter being a relatively new stain commonly used for human
      sperm. Our hypotheses were that (1) SpermBlue allows easier assessment of horse
      sperm morphology and facilitates better identification of sperm abnormalities,
      and (2) sperm morphology classification differs depending on the evaluator's
      experience. Semen was obtained from various horse breeds; 40 samples from
      stallions between 2 and 15 years of age were collected during the 2016 breeding
      season and stored in a 2% buffered formaldehyde solution until processing. For
      each sample, 3 semen smears were made and stained with Diff-Quik, eosin-nigrosin,
      and SpermBlue. All morphological parameters were then evaluated blindly using a
      light microscope by a novice evaluator and a more experienced evaluator. For each
      slide, 200 spermatozoa were examined randomly and classified according to their
      characteristics. For the identification of morphologically normal spermatozoa, no
      significant difference between evaluators was found with any of the staining
      methods used. In contrast, significant differences between evaluators were
      observed in the classification of some anomalies affecting mainly the midpiece
      and the tail. Poor dye fixation was observed with SpermBlue.

PMID- 29198957
TI  - Novel Families of Archaeo-Eukaryotic Primases Associated with Mobile Genetic
      Elements of Bacteria and Archaea.
AB  - Cellular organisms in different domains of life employ structurally unrelated,
      non-homologous DNA primases for synthesis of a primer for DNA replication.
      Archaea and eukaryotes encode enzymes of the archaeo-eukaryotic primase (AEP)
      superfamily, whereas bacteria uniformly use primases of the DnaG family. However,
      AEP genes are widespread in bacterial genomes raising questions regarding their
      provenance and function. Here, using an archaeal primase-polymerase PolpTN2
      encoded by pTN2 plasmid as a seed for sequence similarity searches, we recovered
      over 800 AEP homologs from bacteria belonging to 12 highly diverse phyla. These
      sequences formed a supergroup, PrimPol-PV1, and could be classified into five
      novel AEP families which are characterized by a conserved motif containing an
      arginine residue likely to be involved in nucleotide binding. Functional assays
      confirm the essentiality of this motif for catalytic activity of the PolpTN2
      primase-polymerase. Further analyses showed that bacterial AEPs display a range
      of domain organizations and uncovered several candidates for novel families of
      helicases. Furthermore, sequence and structure comparisons suggest that PriCT-1
      and PriCT-2 domains frequently fused to the AEP domains are related to each other
      as well as to the non-catalytic, large subunit of archaeal and eukaryotic
      primases, and to the recently discovered PriX subunit of archaeal primases.
      Finally, genomic neighborhood analysis indicates that the identified AEPs encoded
      in bacterial genomes are nearly exclusively associated with highly diverse
      integrated mobile genetic elements, including integrative conjugative plasmids
      and prophages.

PMID- 29198959
TI  - Evaluation of Immune Reaction and PD-L1 Expression Using Multiplex
      Immunohistochemistry in HER2-Positive Breast Cancer: The Association With
      Response to Anti-HER2 Neoadjuvant Therapy.
AB  - BACKGROUND: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been
      extensively investigated in breast cancer. Programmed cell death 1 and its ligand
      (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However,
      the combination of TILs with PD-L1 expression has not been well studied in breast
      cancer. PATIENTS AND METHODS: A multi-color immunohistochemical multiplex assay
      simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole
      sections from 123 HER2-positive (HER2+) breast cancers, including 64 treated with
      anti-HER2 neoadjuvant therapy and subsequent resection. RESULTS: PD-L1 expression
      was identified in 88 cases (72%) including 21 (17%) in tumor cells and 67 (55%)
      in immune cells. PD-L1 expression was positively associated with high Nottingham
      grade, high nuclear grade, and a high level of CD8+ and CD163+ cells. Among the
      64 patients who received neoadjuvant therapy, 39 had pathologic complete
      remission (pCR) and 25 had incomplete response. Multivariate analysis showed
      progesterone receptor negativity, HER2/chromosome 17 centromere (CEN17) ratio and
      intratumoral CD8+ cells were significantly associated with pCR. Furthermore, all
      patients with intratumoral CD8+ cells but no PD-L1 expression achieved pCR.
      CONCLUSION: Our data have shown that examination of intratumoral CD8+ cells
      together with PD-L1 expression proves useful in predicting response to anti-HER2
      targeted therapy in patients with HER2+ breast cancer.

PMID- 29198958
TI  - Inhalation anaesthetic isoflurane inhibits the muscarinic cation current and
      carbachol-induced gastrointestinal smooth muscle contractions.
AB  - Gastrointestinal tract motility may be demoted significantly after surgery
      operations at least in part due to anaesthetic agents, but there is no
      comprehensive explanation of the molecular mechanism(s) of such adverse effects.
      Anesthetics are known to interact with various receptors and ion channels
      including several subtypes of transient receptor potential (TRP) channels. Two
      members of the canonical subfamily of TRP channels (TRPC), TRPC4 and TRPC6 are
      Ca2+-permeable cation channels involved in visceral smooth muscle contractility
      induced by acetylcholine, the primary excitatory neurotransmitter in the gut. In
      the present study, we aimed to study the effect of anesthetics on muscarinic
      receptor-mediated excitation and contraction of intestinal smooth muscle. Here we
      show that muscarinic cation current (mICAT) mediated by TRPC4 and TRPC6 channels
      in mouse ileal myocytes was strongly inhibited by isoflurane (0.5mM), one of the
      most commonly used inhalation anesthetics. Carbachol-activated mICAT was reduced
      by 63 +/- 11% (n = 5), while GTPgammaS-induced (to bypass muscarinic receptors)
      current was inhibited by 44 +/- 9% (n = 6). Furthermore, carbachol-induced ileum
      and colon contractions were inhibited by isoflurane by about 30%. We discuss the
      main sites of isoflurane action, which appear to be G-proteins and muscarinic
      receptors, rather than TRPC4/6 channels. These results contribute to our better
      understanding of the signalling pathways affected by inhalation anesthetics,
      which may cause ileus, and thus may be important for the development of novel
      treatment strategies during postoperative recovery.

PMID- 29198960
TI  - [Distinct symptoms and important implications in a 42-year-old man].

PMID- 29198961
TI  - A case of successfully treated relapsing peritoneal dialysis-associated
      peritonitis caused by Gordonia bronchialis in a farmer.
AB  - Gordonia species are aerobic, weakly acid-fast, Gram-positive pathogens that
      rarely cause human infections, usually in immunocompromised patients. It is
      uncommon bacilli in cases of peritoneal dialysis-related peritonitis. The small
      number of infections with Gordonia species reported for humans may be stipulated
      by the difficulty in identifying the organism using conventional techniques.
      Careful review of Gram stains and modified-acid-fast stains should be done, so
      that confusion with other actinomycetes is minimized, pending the genotypic
      identification. Here we report a case that was caused by Gordonia bronchialis and
      thus required different considerations of treatment.

PMID- 29198962
TI  - [Type 1 primary hyperoxaluria: From childhood to adult, how to manage adequately
      medical therapy compliance?]
AB  - We report the cases of three young patients suffering from type 1 primary
      hyperoxaluria, a metabolic genetic disorder characterized by intracellular
      accumulation of oxalate and which may result in end-stage renal disease with
      systemic impairment. A number of effective conservative therapeutic means are
      available for early management of affected children particularly when he is
      growing older. Despite the demonstrated efficacy of conservative therapy,
      compliance represents a major and daily challenge. Monitoring therapeutic
      compliance is thus an important task for physicians in charge of this disease. A
      better understanding of non-compliance causes is required to improve the follow
      up of patients for whom treatment education must be a priority.

PMID- 29198963
TI  - Prenatal phthalate exposure and language development in toddlers from the Odense
      Child Cohort.
AB  - BACKGROUND: Phthalates are a group of chemicals found in a variety of consumer
      products. They have anti-androgenic properties and human studies have reported
      associations between prenatal phthalate exposure and neuropsychological
      development in the offspring despite different cognitive tests, different ages
      and varying timing of exposure. OBJECTIVES: To investigate the association
      between prenatal phthalate exposure and language development in children aged 20
      36months. METHODS: In the Odense Child Cohort, we analyzed 3rd trimester urine
      samples of 518 pregnant women for content of metabolites of diethyl, di-n-butyl,
      diisobutyl, butylbenzyl, di(2-ethylhexyl), and diisononyl phthalate, adjusted for
      osmolality. Language development was addressed using the Danish version of the
      MacArthur-Bates Communicative Development Inventories "Words and Sentences".
      Associations were assessed using logistic regression models comparing children
      below and above the 15th percentile while stratifying by sex and adjusting for
      maternal age and educational level. RESULTS: Phthalate metabolites were
      detectable in all samples although in lower levels than previous studies. Among
      boys, increased prenatal phthalate exposure was associated with lower scores in
      language development; odds ratios for vocabulary score below the 15th percentile
      with doubling in monoethyl phthalate, and summed di-(2-ethylhexyl) phthalate
      metabolites were respectively 1.24 (95% confidence interval: 1.05,1.46), and 1.33
      (1.01,1.75). Similar associations were found for language complexity. No
      associations were found for girls. CONCLUSIONS: Our findings are notable, as
      adverse associations were suggested even in this low-level exposed population,
      with only one spot urine sample for exposure assessment and control for
      confounders. Lower scores in early language development are of relevance to
      health as this test predicts later educational success.

PMID- 29198965
TI  - Telestroke: India's solution to a public health-care crisis.

PMID- 29198966
TI  - The evolving landscape of epilepsy neuropathology.

PMID- 29198964
TI  - Madecassoside protects BV2 microglial cells from oxygen-glucose
      deprivation/reperfusion-induced injury via inhibition of the toll-like receptor 4
      signaling pathway.
AB  - In a previous study, the authors reported that madecassoside (MA) exerted a
      potent neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury
      in rats, mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic
      mechanisms. However, the cellular and molecular bases for its neuroprotective
      effects have not been fully elucidated. In this study, an in vitro ischemic model
      of oxygen-glucose deprivation followed by reperfusion (OGD/R) was used to
      investigate the role of the toll-like receptor 4 (TLR4)/myeloid differentiation
      factor 88 (MyD88)/nuclear factor-kappa B (NF-kappaB) pathway in the
      neuroprotective and anti-inflammatory effects of MA. BV2 microglia viability
      after OGD/R, treated with or without MA, was measured using the MTT assay.
      Messenger RNA and protein expression of pro-inflammatory cytokines (tumor
      necrosis factor alpha [TNF-alpha], interleukin-1beta [IL-1beta], interleukin-6
      [IL-6]) were measured using real-time polymerase chain reaction (RT-PCR) and
      ELISA after OGD/R or lipopolysaccharide treatment. Expression of TLR4/MyD88 and
      NF-kappaB p65 were measured using RT-PCR, Western blotting, and
      immunofluorescence analysis. MA significantly rescued OGD/R-induced cytotoxicity
      in BV2 microglia. Meanwhile, MA suppressed the secretion of pro-inflammatory
      mediators, including TNF-alpha, IL-1beta, and IL-6, induced by OGD/R or
      lipopolysaccharide in BV2 microglia. The mechanism of its neuroprotection and
      anti-inflammation from OGD/R may involve the inhibition of activation of TLR4 and
      MyD88 in BV2 microglia, and the blockage of NF-kappaB p65 nuclear translocation.
      MA exhibited a significant neuroprotective effect against I/R injury in both in
      vivo and in vitro experiments by attenuating microglia-mediated neuroinflammation
      via inhibition of the TLR4/MyD88/NF-kappaB signaling pathway.

PMID- 29198967
TI  - CPR-related organ injuries in pregnant and non-pregnant subjects: Liver. An
      overview of evidence.

PMID- 29198968
TI  - Clustering of Rac1: Selective Lipid Sorting Drives Signaling.
AB  - The ability of lipid-anchored small GTPases to form nanometer-scale lipid domains
      on the cell plasma membrane (PM) is precipitating exciting new insights into
      membrane-anchored protein regulation. A recent article by Remorino et al.
      demonstrates that Rac1, similar to Ras, forms nanoclusters on the PM. The
      implications of these findings are discussed herein.

PMID- 29198969
TI  - Validation of a touchscreen psychomotor vigilance task.
AB  - OBJECTIVE: The purpose of this study was to compare a psychomotor vigilance task
      developed for use on touchscreen devices with the original PVT-192 in conditions
      of acute sleep loss and circadian desynchronization. BACKGROUND: The Psychomotor
      Vigilance Task (PVT) is considered the gold standard fatigue detection test and
      is used frequently in fatigue research. With the rapid development of new
      technologies it is essential to develop a PVT available on different platforms
      such as touchscreen devices. The advantage of such PVT is that it can be
      implemented on small devices and can be easily used in field studies. METHODS:
      Ten participants completed a 5-min PVT (NASA-PVT) on a touchscreen device and a 5
      min PVT on the original PVT-192. On the day of the experiment, participants
      arrived in the lab approximately two hours after their habitual wake time.
      Participants completed a constant routine protocol under dim lighting, while
      maintaining a constant posture. The 5-min PVT-192 and NASA-PVT were taken every
      two hours for at least 24h. RESULTS: The NASA-PVT and PVT-192 were sensitive to
      extended wakefulness in the same manner. The reaction times were slower and the
      lapses were higher as time progressed on both NASA-PVT and PVT-192 (p<0.001).
      Overall, there was a sharp decline in performance after 16h of being awake which
      coincided with the time the participants were usually going to bed and the worst
      performance occurred after 24h of wakefulness for both PVTs (p<0.001).
      CONCLUSIONS: Overall, our data suggest that the NASA-PVT is a valid tool for
      assessing fatigue in field studies.

PMID- 29198970
TI  - The choriocarcinoma cell line JEG-3 upregulates regulatory T cell phenotypes and
      modulates pro-inflammatory cytokines through HLA-G.
AB  - An understanding of the interactions between immune cells and trophoblast cells,
      as well as choriocarcinoma cells, are of extreme importance in reproductive
      immunology and cancer immunology. In this study, we found that the human HLA-G
      positive choriocarcinoma cell line JEG-3 upregulates CD4+CD25hiCD127lo T cells,
      increases the expression of HLA-G+CD4+ and CD8+ T cells, and decreases the
      expression of ILT2+ on CD4+ T cells in resting PBMCs after six days of co
      culture. Expression of HLA-G on JEG-3 cells did not affect regulatory T cell
      phenotypes, but promoted modulation of pro-inflammatory cytokines IFN-gamma, TNF
      alpha and IL-17A. When JEG-3 cells were stimulated with rhIFN-gamma prior to co
      culture, CD4+HLA-G+ T cells were significantly increased, and IFN-gamma and TNF
      alpha elevated. Taken together, the results indicate that JEG-3 cells upregulate
      regulatory T cell phenotypes and modulate the level of pro-inflammatory
      cytokines, which might be important mechanisms in the tumor microenvironment and
      at the feto-maternal interface during pregnancy.

PMID- 29198971
TI  - Characteristics of feeding tube dependency with respect to food aversive
      behaviour and growth.
AB  - The use of feeding tubes in pediatric medical procedures and management has
      dramatically increased over the last three decades. With this increase, the
      prevalence of Feeding Tube Dependency (FTD) - a reliance on enteral feeding
      following medical recovery due to lack of oral intake of nutrition, despite being
      able to eat- has increased too. It has been suggested, that cases with FTD show
      avoidant feeding behaviours such as food refusal, gagging or swallowing
      resistance, but evidence for this hypothesis is scarce. In a German population of
      146 cases requesting feeding tube dependency treatment between 2005 and 2008 the
      frequency of occurrence of avoidant behaviour in FTD cases has been evaluated and
      was correlated to growth. The study includes children under 50 months of age
      being tube fed for at least three months. Parents received the Anamnestic
      Questionnaire for Feeding Disorder and Tube Weaning (AFT), which evaluates
      nutritional supply, tube feeding, feeding disorder symptoms, medical diagnosis,
      growth and psychosocial variables. The study group was comprised of 101 children
      (50 male, 51 female), with a median age of 15 months (IQR: 10-26.5) and a median
      tube feeding duration of 13 months (IQR: 8-27). The most prevalent medical
      diagnoses were congenital malformations (n = 51) and prematurity (n = 27).
      Parents reported daily symptoms of food aversion through all age groups, like
      food refusal 2 (IQR: 1-3), gagging 1 (IQR: 0-3), vomiting 1 (0.1-2) and total
      symptoms 6 (5-11). Vomiting was negatively correlated with weight and length
      percentile and head circumference. Cases with FTD show frequent and persistent
      food avoidant behaviors, which may be explain the need for specific psychological
      treatment during transitioning from tube dependency to oral eating.

PMID- 29198972
TI  - Analysis of codon usage bias of Crimean-Congo hemorrhagic fever virus and its
      adaptation to hosts.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a negative-sense, single
      stranded RNA virus with a three-segmented genome that belongs to the genus
      Nairovirus within the family Bunyaviridae. CCHFV uses Hyalomma ticks as a vector
      to infect humans with a wide range of clinical signs, from asymptomatic to Zika
      like syndrome. Despite significant progress in genomic analyses, the influences
      of viral relationships with different hosts on overall viral fitness, survival,
      and evading the host's immune systems remain unknown. To better understand the
      evolutionary characteristics of CCHFV, we performed a comprehensive analysis of
      the codon usage pattern in 179 CCHFV strains by calculating the relative
      synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation
      index (CAI), and other indicators. The results indicate that the codon usage bias
      of CCHFV is relatively low. Several lines of evidence support the hypothesis that
      a translation selection factor is shaping codon usage pattern in this virus. A
      correspondence analysis (CA) showed that other factors, such as base composition,
      aromaticity, and hydrophobicity may also be involved in shaping the codon usage
      pattern of CCHFV. Additionally, the results from a comparative analysis of RSCU
      between CCHFV and its hosts suggest that CCHFV tends to evolve codon usage
      patterns that are comparable to those of its hosts. Furthermore, the selection
      pressures from Homo sapiens, Bos taurus, and Ovis aries on the CCHFV RSCU
      patterns were dominant when compared with selection pressure from Hyalomma spp.
      vectors. Taken together, both natural selection and mutation pressure are
      important for shaping the codon usage pattern of CCHFV. We believe that such
      findings will assist researchers in understanding the evolution of CCHFV and its
      adaptation to its hosts.

PMID- 29198973
TI  - Association of Burnout With Emotional Intelligence and Personality in Surgical
      Residents: Can We Predict Who Is Most at Risk?
AB  - OBJECTIVES: Burnout is common among surgical residents and may be related to
      personality characteristics, emotional intelligence (EI), or work experiences.
      DESIGN: Longitudinal cohort study over 1 year. SETTING: Tertiary academic medical
      centers in the Northeast. PARTICIPANTS: All general surgery residents in 2
      programs (n = 143) were invited to complete an electronic survey at 3 time
      points; 88, 64, and 69 residents completed the survey (overall response rate
      52%). RESULTS: Severe burnout was observed in 51% of residents (n = 41). Higher
      scores were associated with female sex (p = 0.02). Burnout scores were highest at
      the beginning and end of the academic year; EI and personality scores remained
      stable. On bivariate analysis, high EI score (p < 0.001), agreeableness and
      emotional stability personality features (p = 0.003), and positive job
      experiences (p < 0.01) were protective against burnout. Higher EI and positive
      work experiences were independent predictors of lower burnout (p < 0.01) after
      multivariable adjustment. CONCLUSIONS: Surgical residents have high levels of
      burnout. Higher EI and positive work experiences are associated with lower
      burnout. Focused interventions to improve EI and optimize the work environment
      may prevent or lessen burnout.

PMID- 29198974
TI  - Low Acceptability of Certain Contraceptive Methods among Young Women.
AB  - STUDY OBJECTIVE: To examine what predicts low personal acceptability of 4
      different contraceptive methods among young women. DESIGN: Cross-sectional
      survey. SETTING: Urban adolescent contraception clinic in Colorado. PARTICIPANTS:
      Female clinic patients ages 13-24 initiating contraception from August 2011 to
      April 2012. INTERVENTIONS AND MAIN OUTCOME MEASURES: Survey participants reported
      their personal acceptability for oral contraceptive pills, depot
      medroxyprogesterone, contraceptive implants, and intrauterine devices on a scale
      from 0 (low) to 10 (high). Responses of 0-4 were categorized as low personal
      acceptability. Demographic characteristics, reproductive history, and perceived
      contraceptive satisfaction of friends and family members were incorporated into
      multivariable and hierarchical logistic regression models to determine distinct
      predictors of low personal acceptability for each method. RESULTS: Surveys were
      completed by 1067 women. Participants' mean age was 20 (+/-2.6) years. Half
      (552/1067) were white, 26% (277/1067) Hispanic, and 8.5% (91/1067) black. Of
      participants who were aware of oral contraceptive pills 52% (535/1037) reported
      low acceptability of this method compared with 74% (645/876) of those aware of
      depot medroxyprogesterone. Fewer reported low acceptability of intrauterine
      devices (37% or 303/825) or implant (43% or 356/839), although fewer overall
      participants had heard of these methods. Each method had unique predictors of low
      personal acceptability, however, for all method models, significant predictors
      included knowing someone who had become pregnant while using that method or
      having a friend who dislikes that method. CONCLUSION: Young women in this study
      with low personal acceptability of the 4 most common contraceptive methods had
      distinct demographic and reproductive health characteristics. Perceived negative
      experiences of friends and family members using contraception appeared most
      influential.

PMID- 29198975
TI  - Improvement of bovine in vitro embryo production by ovarian follicular wave
      synchronization prior to ovum pick-up.
AB  - This study evaluated the effects of the synchronization of ovarian follicular
      wave emergence on the efficiency of in vitro embryo production. Bos indicus cows
      (n = 20) were divided into two groups (control vs. synchronization) and subjected
      to repeated ovum pick-up (OPU) sessions (8 replicates each, with an interval of
      21 days in a 2 * 2 crossover design) and subsequent in vitro embryo production.
      Cows in the control group (n = 10) were submitted to OPU procedures without any
      stimulation every 21 days. Animals in the synchronization group received a
      protocol-based progesterone implant, estradiol benzoate and prostaglandin on a
      random day of the estrus cycle (Day 0) and the OPU was performed on Day 5. After
      in vitro production, embryos were transferred to recipients synchronized at a
      fixed time and the diagnosis was performed 60 days later. An evaluation of the
      parameters for each OPU session revealed that donors that received the
      synchronization protocol pre-OPU showed a greater number of embryos (5.9 +/- 0.5
      vs. 4.5 +/- 0.4; P = 0.037), higher rate of embryo production (45.8% vs. 38.5%; P
      = 0.001) and higher mean number of conceptions per group (2.2 +/- 0.2 vs. 1.6 +/-
      0.2; P = 0.07) in relation to the group that did not receive hormonal treatment.
      We concluded that synchronization of the follicular wave prior to OPU showed
      positive effects on in vitro embryo production as well as on pregnancy rates.

PMID- 29198976
TI  - Ligand-free method to produce the anti-angiogenic recombinant Galectin-3
      carbohydrate recognition domain.
AB  - Galectin-3 (Gal3) is involved in many physiological processes related to tumor
      growth, such as promoting angiogenesis, cell migration/invasion, resistance to
      apoptosis and immune response modulation. Usually the overexpression of Gal3 is a
      poor prognostic marker for cancer patients. Recombinant Gal3 carbohydrate domain
      (Gal3C) has been proposed as a useful tool to inhibit angiogenesis. So far, all
      production protocols reported for Gal3C production have used proteolytic cleavage
      of full length Gal3 and/or affinity-based purification. This involves dialysis, a
      time consuming step used to eliminate the elution ligand, usually lactose. In
      this report, we describe an alternative method to produce human recombinant Gal3C
      in E. coli, purified with cationic exchange and size exclusion chromatography.
      The recombinant protein was characterized using circular dichroism and nuclear
      magnetic resonance, showing a beta sheet enriched well-folded globular structure.
      The average yield obtained was 26 mg/L of broth and the purity was above 99%. The
      anti-angiogenic activity was assessed in vitro and showed a reduction of 70% and
      77% in endothelial cells tubule formation upon treatment with 10 and 20 MUg/mL,
      respectively and also had no impact on cell viability. The method described here
      is more suitable for both laboratory and industrial production of the potential
      anti-tumor Gal3C.

PMID- 29198977
TI  - Robust output feedback stabilization for a flexible marine riser system.
AB  - The aim of this paper is to develop a boundary control for the vibration
      reduction of a flexible marine riser system in the presence of parametric
      uncertainties and system states obtained inaccurately. To this end, an adaptive
      output feedback boundary control is proposed to suppress the riser's vibration
      fusing with observer-based backstepping, high-gain observers and robust adaptive
      control theory. In addition, the parameter adaptive laws are designed to
      compensate for the system parametric uncertainties, and the disturbance observer
      is introduced to mitigate the effects of external environmental disturbance. The
      uniformly bounded stability of the closed-loop system is achieved through
      rigorous Lyapunov analysis without any discretisation or simplification of the
      dynamics in the time and space, and the state observer error is ensured to
      exponentially converge to zero as time grows to infinity. In the end, the
      simulation and comparison studies are carried out to illustrate the performance
      of the proposed control under the proper choice of the design parameters.

PMID- 29198978
TI  - Controllability of fractional higher order stochastic integrodifferential systems
      with fractional Brownian motion.
AB  - This paper presents a new set of sufficient conditions for controllability of
      fractional higher order stochastic integrodifferential systems with fractional
      Brownian motion (fBm) in finite dimensional space using fractional calculus,
      fixed point technique and stochastic analysis approach. In particular, we discuss
      the complete controllability for nonlinear fractional stochastic
      integrodifferential systems under the proved result of the corresponding linear
      fractional system is controllable. Finally, an example is presented to illustrate
      the efficiency of the obtained theoretical results.

PMID- 29198980
TI  - Applications of pHLIP Technology for Cancer Imaging and Therapy: (Trends in
      Biotechnology 35, 653-664, 2017).

PMID- 29198979
TI  - Bone volume fraction and structural parameters for estimation of mechanical
      stiffness and failure load of human cancellous bone samples; in-vitro comparison
      of ultrasound transit time spectroscopy and X-ray MUCT.
AB  - Conventional mechanical testing is the 'gold standard' for assessing the
      stiffness (N mm-1) and strength (MPa) of bone, although it is not applicable in
      vivo since it is inherently invasive and destructive. The mechanical integrity of
      a bone is determined by its quantity and quality; being related primarily to bone
      density and structure respectively. Several non-destructive, non-invasive, in
      vivo techniques have been developed and clinically implemented to estimate bone
      density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric
      (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS)
      parameters of velocity and attenuation are dependent upon both bone quantity and
      bone quality, although it has not been possible to date to transpose one
      particular QUS parameter into separate estimates of quantity and quality. It has
      recently been shown that ultrasound transit time spectroscopy (UTTS) may provide
      an accurate estimate of bone density and hence quantity. We hypothesised that
      UTTS also has the potential to provide an estimate of bone structure and hence
      quality. In this in-vitro study, 16 human femoral bone samples were tested
      utilising three techniques; UTTS, micro computed tomography (MUCT), and
      mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV)
      and two novel structural parameters, inter-quartile range of the derived transit
      time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP).
      MUCT was utilised to derive BV/TV along with several bone structure parameters. A
      destructive mechanical test was utilised to measure the stiffness and strength
      (failure load) of the bone samples. BV/TV was calculated from the derived transit
      time spectrum (TTS); the correlation coefficient (R2) with MUCT-BV/TV was 0.885.
      For predicting mechanical stiffness and strength, BV/TV derived by both MUCT and
      UTTS provided the strongest correlation with mechanical stiffness (R2=0.567 and
      0.618 respectively) and mechanical strength (R2=0.747 and 0.736 respectively).
      When respective structural parameters were incorporated to BV/TV, multiple
      regression analysis indicated that none of the MUCT histomorphometric parameters
      could improve the prediction of mechanical stiffness and strength, while for
      UTTS, adding TTMP to BV/TV increased the prediction of mechanical stiffness to
      R2=0.711 and strength to R2=0.827. It is therefore envisaged that UTTS may have
      the ability to estimate BV/TV along with providing an improved prediction of
      osteoporotic fracture risk, within routine clinical practice in the future.

PMID- 29198981
TI  - Does the proposed removal of mitotic count as a prognostic indicator in melanoma,
      accurately reflect the risk profile for metastasis in UK patients?

PMID- 29198982
TI  - Robotic-assisted DIEP flap harvest: A feasibility study on cadaveric model.

PMID- 29198983
TI  - Concentration-dependent supramolecular patterns of C3 and C2 symmetric molecules
      at the solid/liquid interface.
AB  - Here we report on a scanning tunnelling microscopy (STM) investigation on the
      self-assembly of C3- and C2-symmetric molecules at the solution/graphite
      interface. 1,3,5-tris((E)-2-(pyridin-4-yl)vinyl)benzene and 1,1,2,2-tetrakis(4
      (pyridin-4-yl)phenyl)ethane are used as model systems. These molecules displayed
      a concentration dependent self-assembly behaviour on graphite, resulting in
      highly ordered supramolecular structures, which are stabilized jointly by van der
      Waals substrate-adsorbate interactions and in-plane intermolecular H-bonding.
      Denser packing is obtained when applying a relatively high concentration solution
      to the basal plane of the surface whereas a less dense porous network is observed
      upon lowering the concentration. We show that the molecular conformation does not
      influence the stability of the self-assembly and a twisted molecule can pack into
      dense and porous architectures under the concentration effect.

PMID- 29198984
TI  - Relation of an Echocardiographic-Based Cardiac Calcium Score to Mitral Stenosis
      Severity and Coronary Artery Disease in Patients with Severe Aortic Stenosis.
AB  - Patients with calcific aortic stenosis (AS) often have diffuse cardiac
      calcification involving the mitral valve apparatus and coronary arteries. We
      examined the association between global cardiac calcification quantified by a
      previously validated echocardiographic calcium score (eCS) with the severity of
      mitral stenosis (MS) and coronary artery disease (CAD) in patients with a
      clinical diagnosis of severe calcific AS. In this sample of 147 patients (mean
      age 81 +/- 9 years, 50% male), 81 patients (55%) were determined by
      echocardiography to have some degree of MS. Higher mean eCS was observed in
      patients with more severe MS (r = 0.54, p < 0.0001). Higher eCS was also
      inversely associated with mitral valve area (r = -0.31, p = 0.001) and positively
      associated with mitral valve mean pressure gradient (r = 0.46, p < 0.0001) and
      mitral valve peak flow velocity (r = 0.55, p < 0.0001). The area under the
      receiver operating characteristic curve for using eCS to predict the presence of
      MS was 0.76. An eCS >= 8 predicted MS with a sensitivity of 68%, specificity of
      76%, positive predictive value of 77%, and negative predictive value of 66%. High
      eCS, relative to low eCS, was associated with 2.70 times the adjusted odds of CAD
      (odds ratio = 2.70, 95% confidence interval 1.02 to 7.17). In conclusion, global
      cardiac calcification is associated with MS and CAD in patients with severe
      calcific AS, and eCS shows ability to predict the presence of MS. This study
      suggests that a simple eCS may be used as part of a risk-stratification tool in
      patients with severe calcific aortic valve stenosis.

PMID- 29198985
TI  - Clinical and Psychological Drivers of Perceived Health Status in Adults With
      Congenital Heart Disease.
AB  - The factors having the greatest impact on self-reported health status in adults
      with congenital heart disease (ACHD) remain incompletely studied. We conducted a
      single-site, cross-sectional study of ACHD patients followed at the Center for
      ACHD at Washington University School of Medicine, including retrospectively
      gathered clinical data and psychometric and health status assessments completed
      at the time of enrollment. To identify primary drivers of perceived health
      status, we investigated the impact of the demographic, clinical, and
      psychological variables on self-reported health status as assessed using the Rand
      36-Item Short Form Health Survey. Variables with significant associations within
      each domain were considered jointly in multivariable models constructed via
      stepwise selection. There was domain-specific heterogeneity in the variables
      having the greatest effect on self-reported health status. Depression was
      responsible for the greatest amount of variability in health status in all
      domains except physical functioning. In the physical functioning domain,
      depression remained responsible for 5% of total variability, the third most
      significant variable in the model. In every domain, depression more strongly
      influenced health status than did any cardiac-specific variable. In conclusion,
      depression was responsible for a significant amount of heterogeneity in all
      domains of self-perceived health status. Psychological variables were better
      predictors of health status than clinical variables.

PMID- 29198986
TI  - Australian Trends in Procedural Characteristics and Outcomes in Patients
      Undergoing Percutaneous Coronary Intervention for ST-Elevation Myocardial
      Infarction.
AB  - Over the last decade, systems of care for ST-elevation myocardial infarction
      (STEMI) have evolved to try to improve outcomes and timely access to percutaneous
      coronary intervention (PCI). There have also been advances in PCI techniques and
      adjunctive pharmacotherapies. In this study, we sought to determine temporal
      changes in practices and clinical outcomes of PCI in patients with STEMI. We
      prospectively collected data on 8,412 consecutive patients undergoing PCI for
      STEMI between 2005 and 2016 in the multicenter Melbourne Interventional Group
      registry. Data were divided by procedure year for trends analysis. The primary
      end point was 30-day mortality. Patient demographics and comorbidities including
      smoking and diabetes have remained stable. The volume of primary PCI performed
      within 12 hours of symptom onset has significantly risen (65.7% to 80.1%, p <
      0.01). The proportion of patients achieving the recommended door-to-balloon time
      <=90 minutes has also risen (37.6% to 59.0%, p < 0.01). Patient complexity has
      also increased with more patients after out-of-hospital cardiac arrest with STEMI
      now being treated with PCI (2.6% to 9.1%, p < 0.01). A shift from mainly femoral
      to radial access and from bare-metal to drug-eluting stent use was seen.
      Glycoprotein IIb/IIIa inhibitors are being used less frequently with increasing
      use of newer antiplatelet agents. Thirty-day mortality has remained low
      throughout the study period at 6.5% overall. In conclusion, although timely
      access to primary PCI has improved, mortality rates have remained unchanged, but
      remain low and compare favorably with international data. Australian PCI practice
      has overall evolved in response to evidence and emergence of new adjunctive
      device and pharmacotherapies.

PMID- 29198987
TI  - Energy landscape of the intact and destabilized FMO antennas from C. tepidum and
      the L122Q mutant: Low temperature spectroscopy and modeling study.
AB  - We discuss the excitonic energy landscape of the typically studied wild-type (WT)
      Fenna-Matthews-Olson (FMO) antenna protein from the green sulfur bacterium
      Chlorobaculum tepidum (referred to as WTM), which is described as a mixture of
      intact (WTI) and destabilized (WTD) complexes. Optical spectra of WTM and the
      L122Q mutant (where leucine 122 near BChl 8 is replaced with glutamine) are
      compared to WTI FMO. We show that WTM and L122Q samples are mixtures of two
      subpopulations of proteins, most likely induced by protein conformational changes
      during the isolation/purification procedures. Absorption, emission, and HB
      spectra of WTM and L122Q mutant are very similar, in which the low-energy trap
      (revealed by the nonresonant HB spectra) shifts to higher energies as a function
      of fluence, supporting a mixture model. No fluence-dependent shift is observed in
      the WTI FMO trimers. New Hamiltonians are provided for WTI and WTD proteins.
      Resonant HB spectra show that the internal energy relaxation times in the WTM and
      L122Q mutant are similar, and depend on excitation frequency. Fast average
      relaxation times (excited state lifetimes) are observed for burning into the main
      broad absorption band near 805nm. Burning at longer wavelengths reveals slower
      total dephasing times. No resonant bleach is observed at lambdaB<=803nm, implying
      much faster (femtosecond) energy relaxation in this spectral range in agreement
      with 2D electronic spectroscopy frequency maps.

PMID- 29198988
TI  - Sensing and Transmitting Intracellular Amino Acid Signals through Reversible
      Lysine Aminoacylations.
AB  - Amino acids are known regulators of cellular signaling and physiology, but how
      they are sensed intracellularly is not fully understood. Herein, we report that
      each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency
      through catalyzing the formation of lysine aminoacylation (K-AA) on its specific
      substrate proteins. At physiologic levels, amino acids promote ARSs bound to
      their substrates and form K-AAs on the E-amine of lysines in their substrates by
      producing reactive aminoacyl adenylates. The K-AA marks can be removed by
      deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that
      involved in deacetylation. These dynamically regulated K-AAs transduce signals of
      their respective amino acids. Reversible leucylation on ras-related GTP-binding
      protein A/B regulates activity of the mammalian target of rapamycin complex 1.
      Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We
      discovered non-canonical functions of ARSs and revealed systematic and functional
      amino acid sensing and signal transduction networks.

PMID- 29198989
TI  - Effect of creatinine and cystatin C measurement variations on calculated
      estimated glomerular filtration rate variations and the theoretical impact on
      kidney disease stage classification: A retrospective study.
AB  - BACKGROUND: The estimated glomerular filtration rate (eGFR) is an important
      parameter in the management of patients with kidney diseases, yet eGFR quality
      goals are lacking. We examined the uncertainties in eGFR determinations and
      assessed their impact on patient classifications, aiming to set eGFR quality
      goals. METHODS: Adult patients undergoing creatinine concentration assessments at
      our hospital, between June 2014 and October 2016, were included (N=285,982).
      Using 7 eGFR equations, we calculated the imprecisions in the eGFR, based on the
      imprecisions in determining creatinine and/or cystatin C concentrations. The
      uncertainties in the eGFR were expressed as functions of creatinine and/or
      cystatin C concentration uncertainties. Subsequently, the number of ambiguous
      cases was assessed, based on the calculated uncertainty in the eGFR. RESULTS:
      Uncertainties in the eGFRs varied according to the eGFR calculation equation
      used. Although a 0.8% expanded uncertainty in the eGFR caused a 3.5% ambiguous
      case rate, a 10% expanded uncertainty resulted in a 42.3% rate of ambiguous
      cases. To meet minimal quality requirements, creatinine imprecision should be
      <=3.0%. CONCLUSIONS: Even a low level of uncertainty in the eGFR may cause
      noticeable impacts on patient classifications. Laboratory physicians should be
      aware, and cautious, of the uncertainties in eGFR calculations.

PMID- 29198990
TI  - Prognostic and clinicopathological value of Nanog in hepatocellular carcinoma: A
      meta-analysis.
AB  - BACKGROUND AND AIMS: Recently, studies indicate that Nanog is over-expressed in
      hepatocellular carcinoma (HCC); however, the relationship between Nanog
      expression and clinicopathological and prognostic value remains controversial.
      Therefore, we conducted a meta-analysis to explore the role of Nanog in HCC.
      METHODS: Articles were included from PubMed, Cochrane Library, Web of Science,
      EMBASE database, Chinese CNKI, and the Chinese WanFang database. The
      relationships between Nanog expression, clinicopathological features, and
      survival rate were calculated. Pooled odds ratios (ORs) and hazard ratios (HRs)
      with 95% confidence intervals (CIs) were calculated with STATA14.2. RESULTS: A
      total of 845 patients from 9 articles were enrolled. Positive Nanog expression
      was correlated with HBsAg, differentiation, and TNM stage, although it was not
      related to gender, age, alpha-fetoprotein (AFP), tumor size, tumor number, liver
      cirrhosis, and vascular invasion. Positive Nanog expression indicates a poor 3
      year and 5-year overall survival and disease-free survival rate. CONCLUSION: The
      results show that Nanog expression was related to HBsAg, differentiation, and TNM
      stage in HCC. Nanog may be an unfavorable prognostic biomarker for HCC.

PMID- 29198991
TI  - Interleukin-23 receptor polymorphism (rs10889677 A/C) in ankylosing spondylitis:
      Meta-analysis in Caucasian and Asian populations.
AB  - BACKGROUND: The association between interleukin-23 receptor (IL23R) gene
      rs10889677 polymorphism and ankylosing spondylitis (AS) susceptibility was
      inconsistent in the recent literatures. A systematic review and meta-analysis was
      therefore performed. METHODS: Online electronic databases were searched for
      relevant studies published up to November 2017. Meta-analyses were performed for
      the comparisons of allele (A versus C) and multiple genetic models, including
      dominant, recessive, heterozygous, and homozygous models using fixed or random
      effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were
      utilized to assess the potential relationship. RESULTS: Sixteen studies
      containing 19 separate comparisons, totaling 6450 cases and 8009 controls were
      included. A significant association between rs10889677 A allele and AS
      susceptibility was detected (OR=1.136, 95%CI=1.043-1.236, P=0.003). Stratified
      analysis by ethnicity indicated that rs10889677 A allele was significantly
      associated with AS in Europeans (OR=1.192, 95%CI=1.080-1.315, P<0.001), but not
      Asians (OR=1.045, 95%CI=0.913-1.197, P=0.523). In addition, there were no
      significant associations between rs10889677 polymorphism and AS susceptibility in
      any of dominant, recessive, homozygous and heterozygous models. CONCLUSION: This
      meta-analysis demonstrates that IL23R gene rs10889677 A allele confers increased
      risk of AS in Europeans, but its role in Asian populations needs further
      exploration.

PMID- 29198992
TI  - Cardiac troponin and adverse outcomes in atrial fibrillation: A meta-analysis.
AB  - BACKGROUND: The prognostic value of cardiac troponin elevation in atrial
      fibrillation (AF) is unclear. OBJECTIVE: To investigate the association of
      cardiac troponin elevation with adverse outcomes in AF by conducting a meta
      analysis. METHODS: We systematically searched the PubMed and Embase databases
      until April 2017 for studies assessing the association of cardiac troponin-T
      (cTnT) or troponin-I (cTnI) elevation with adverse outcomes in AF. The outcome
      measures were all-cause mortality and major adverse cardiac events (MACEs: death,
      stroke, myocardial infarction, pulmonary embolism, major bleeding, or
      revascularization). RESULTS: Six studies involving 22,697 AF patients were
      identified. Meta-analysis showed that AF with elevated cardiac troponin was
      independently associated with increased risk of all-cause mortality (HR 2.04; 95%
      CI 1.56-2.67) and MACEs (HR 1.93; 95% CI 1.61-2.30). Furthermore, the prognostic
      value of cardiac troponin elevation was consistently found irrespective of method
      determination, type of troponin measured, sample size, and study quality
      subgroup. CONCLUSIONS: AF with cardiac troponin elevation was independently
      associated with increased risk of all-cause mortality and MACEs. Therefore,
      determination of troponin should be considered for risk stratification in AF.

PMID- 29198993
TI  - Cardiovascular benefits of combined interval training and post-exercise nutrition
      in type 2 diabetes.
AB  - AIM: The purpose of this study was to examine whether the combination of high
      intensity interval training (HIIT) and post-exercise protein supplementation
      would improve cardiovascular outcomes in individuals with T2D. METHODS: In a
      double-blind controlled trial, fifty-three adults with T2D (free of CVD and not
      on exogenous insulin) were randomized to 12weeks of cardio and resistance-based
      HIIT (4-10*1min at 90% maximal heart rate) with post-exercise milk, milk-protein,
      or placebo supplementation, thrice weekly. Before and after, carotid and femoral
      artery intima media thickness (IMT) and femoral flow profiles were assessed using
      high-resolution ultrasound. Central and peripheral arterial stiffness were
      assessed by pulse wave velocity (PWV), and resting and maximal heart rate rates
      were measured. RESULTS: After 12weeks of HIIT femoral IMT (Pre: 0.84+/-0.21mm vs.
      Post: 0.81+/-0.16mm, p=0.03), carotid-femoral PWV (Pre: 10.1+/-3.2m/s vs. Post:
      8.6+/-1.8m/s, p<0.01) and resting heart rate (Pre: 70.4+/-10.8bpm vs. Post:
      67.8+/-8.6 bpm, p=0.01) were all significantly lower. There were no differences
      between nutrition groups (all significant main effects of time) for all outcomes.
      CONCLUSION: HIIT reduces femoral IMT, arterial stiffness and resting heart rate
      in individuals with T2D. The addition of post-exercise milk or protein to HIIT
      did not have additive effects for improving cardiovascular outcomes in the
      present study. Taken together, HIIT alone may be an effective means to reduce the
      burden of cardiovascular complications in T2D.

PMID- 29198995
TI  - Challenges in defining, diagnosing, and treating diabetic gastroparesis.

PMID- 29198994
TI  - Dietary quality and markers of inflammation: No association in youth with type 1
      diabetes.
AB  - BACKGROUND: Systemic inflammation is a key process underlying cardiovascular
      disease (CVD) development, and CVD risk is significantly elevated in persons with
      type 1 diabetes (T1D). Youth with T1D exhibit increased levels of inflammation.
      Studies in persons without diabetes suggest that dietary quality influences
      inflammation, yet little is known about dietary influences on inflammation in
      youth with T1D. METHODS: This study evaluated the association of four distinct
      dietary quality indices (Dietary Approaches to Stop Hypertension (DASH), Healthy
      Eating Index 2010 (HEI2010), modified KIDMED and Total Antioxidant Capacity
      (TAC)) with biomarkers of inflammation (C-reactive protein (CRP), fibrinogen and
      interleukin-6 (IL-6)) in a sample of 2520 youth with T1D participating in the
      SEARCH for Diabetes in Youth Study. RESULTS: Average diet quality was moderate to
      poor, with mean scores of 43 (DASH, range 0-80), 55 (HEI2010, range 0-100), 3.7
      (mKIDMED, range 3-12) and 7237 (TAC). None of the four diet quality scores was
      associated with the selected biomarkers of inflammation in any analyses.
      Evaluation of a non-linear relationship or interactions with BMI or levels of
      glycemic control did not alter the findings. Replication of analyses using
      longitudinal data yielded consistent findings with our cross-sectional results.
      CONCLUSIONS: Biomarkers of inflammation in youth with T1D may not be directly
      influenced by dietary intake, at least at the levels of dietary quality observed
      here. More work is needed to understand what physiologic mechanisms specific to
      persons with T1D might inhibit the generally beneficial influence of high dietary
      quality on systemic inflammation observed in populations without diabetes.

PMID- 29198996
TI  - The relationship of health literacy to diabetes status differs by sex in older
      adults.
AB  - OBJECTIVE: Lower health literacy is associated with higher rates of mortality and
      chronic disease. It remains unclear whether health literacy is associated with
      diabetes and/or hyperglycemia in older adults, and if this relationship differs
      by sex. RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of
      2510 older adults in the Health, Aging and Body Composition (Health ABC) Study
      who had both a Rapid Estimate of Adult Literacy in Medicine (REALM) measurement
      and diabetes status available. Sex-stratified logistic regression models were
      used to analyze the relationship of health literacy categories (low, medium, and
      high) to diabetes status, adjusting for key covariates. Secondary analyses
      examined the relationship of health literacy to glycemic markers (A1C, fasting
      blood glucose). RESULTS: Among participants in the Health ABC cohort, 429 had
      diabetes. Mean age was 76years old and 45% were female. Men with diabetes more
      commonly had low health literacy levels than men without diabetes (10.1% versus
      9.3%, p=0.02). Similar results were seen among women (14.7% versus 6.1%, p<0.01).
      In a model adjusting for age, race, income, education, BMI, smoking, and alcohol
      use, women with low versus high health literacy had a two-fold higher likelihood
      of diabetes (OR=2.2; 95% CI 1.1-4.3). No significant relationship was observed in
      men. Progressively lower categories of health literacy were associated with
      higher age-adjusted mean A1C and fasting blood glucose levels in women (both p
      for trend <0.01) but not men. CONCLUSIONS: In this large, ethnically diverse
      sample of community-dwelling older adults, lower health literacy level is related
      to a greater likelihood of diabetes and higher A1C and fasting blood glucose
      levels in women-but not in men-after adjusting for age, race, and other
      demographic and lifestyle factors. Future studies are needed to assess mechanisms
      underlying this relationship and if interventions to improve health literacy are
      effective in reducing the burden of diabetes, particularly in women.

PMID- 29198997
TI  - A Reanalysis of the RIVUR Trial Using a Risk Classification System.
AB  - PURPOSE: The RIVUR (Randomized Intervention for Children with Vesicoureteral
      Reflux) trial showed a 50% decrease in the risk of urinary tract infection
      recurrence in children with reflux receiving continuous antibiotic prophylaxis.
      We reanalyzed the RIVUR data with the purpose of using a risk classification
      system to identify children who are more likely to benefit from continuous
      antibiotic prophylaxis. MATERIALS AND METHODS: Data from 607 children enrolled in
      the RIVUR trial were obtained from the National Institute of Diabetes and
      Digestive and Kidney Diseases Central Repository and analyzed. We stratified
      these children into low and high risk categories. The proportion of children and
      risk of urinary tract infection recurrence in the stratified treatment groups
      were compared. RESULTS: Of the children 385 (63.9%) were stratified into the low
      risk and 217 (36.1%) into the high risk category. The proportions of children
      with urinary tract infection recurrence were not significantly different in the
      low risk category between the placebo and continuous antibiotic prophylaxis
      groups (p = 0.151), while urinary tract infection recurrence was significantly
      higher in the placebo group (31.5% vs 11.4%, p = 0.001) for high risk children.
      Furthermore, high risk children on placebo had a 3.7-fold increased risk of
      urinary tract infection recurrence during 2 years of followup compared to those
      on continuous antibiotic prophylaxis. CONCLUSIONS: Although the RIVUR trial
      concluded that children with vesicoureteral reflux benefit from continuous
      antibiotic prophylaxis, our reanalysis of the data demonstrates that high risk
      children benefit more, with a number needed to treat of 5 compared to 18 in low
      risk children. The clinical implications of these findings suggest a need to
      refine current indications for continuous antibiotic prophylaxis in children with
      reflux, supporting a shift toward a "selective" risk based approach for
      management.

PMID- 29198998
TI  - Surgical Approaches and Long-Term Outcomes in Adults with Complex Reoperative
      Hypospadias Repair.
AB  - PURPOSE: Patients with failed hypospadias repair are a challenging population for
      pediatric and reconstructive urologists. We describe our long-term outcomes and
      factors associated with complications of repeat hypospadias repair. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 32 adult patients with a
      history of hypospadias repair who required subsequent urethroplasty between 2002
      and 2012. Data on the presenting complaint, past medical and surgical history,
      demographic data, surgical approach, intraoperative findings and complications
      were collected and analyzed. RESULTS: Median patient age at urethroplasty was 32
      years. Stricture of the penile urethra was the most common presentation.
      Urethroplasty was done in 30 patients as stricture treatment, 1 underwent
      perineal urethrostomy and 1 underwent diverticulectomy. Two-stage repair was
      performed in 90% of the men who underwent urethroplasty. The initial success rate
      was 83% in patients who underwent 1 or 2-stage urethroplasty. At a median
      followup of 9.5 years complications included 4 recurrent strictures and 1
      fistula. Patient age, previous interventions, stricture length, hair present at
      the time of repair, the need to excise the urethral plate and the number of
      stages were not associated with complications or recurrence. If a graft was
      required, skin grafts were significantly associated with recurrence compared to
      buccal mucosa grafts. CONCLUSIONS: Excellent outcomes can be achieved using a 2
      stage approach with replacement or augmentation of the urethral plate in adults
      with failed hypospadias repair. In our experience buccal mucosa appears to be
      associated with fewer complications and less stricture recurrence than skin
      grafts.

PMID- 29198999
TI  - Society for Fetal Urology Classification vs Urinary Tract Dilation Grading System
      for Prognostication in Prenatal Hydronephrosis: A Time to Resolution Analysis.
AB  - PURPOSE: The Urinary Tract Dilation grading system for prenatal hydronephrosis
      was introduced to address potential shortcomings of the Society for Fetal Urology
      classification. Hydronephrosis resolution is an important patient outcome and is
      frequently discussed during family counseling. We compared these 2 grading
      systems and their ability to predict time to hydronephrosis resolution. MATERIALS
      AND METHODS: We prospectively screened 855 patients with prenatal hydronephrosis
      due to ureteropelvic junction obstruction-like hydronephrosis, nonrefluxing
      primary megaureter or vesicoureteral reflux between 2009 and 2015. Of the
      patients 454 were excluded due to surgery, late referral, absence of postnatal
      dilatation or presence of other anomalies, resulting in 401 eligible patients (of
      whom 81% were male) to be included for analyses. Hydronephrosis grades collected
      at baseline and last followup were compared to identify resolution trends through
      time. Hydronephrosis resolution was defined as renal pelvis anteroposterior
      diameter 10 mm or less at last followup. Time to resolution was analyzed using
      Cox proportion regression. RESULTS: Of 401 patients 328 (82%) had resolution
      during a mean +/- SD followup of 24 +/- 18 months (maximum 107). Cumulative
      resolution rate at 3 years was 98% for Society for Fetal Urology grade I
      hydronephrosis, 87% for grade II, 76% for grade III and 57% for grade IV. The 3
      year hydronephrosis resolution rate was 90% for Urinary Tract Dilation postnatal
      grade 1 (low risk), 81% for grade 2 (intermediate risk) and 71% for grade 3 (high
      risk). CONCLUSIONS: Patients with distinctive baseline hydronephrosis grades
      (classified by Society for Fetal Urology or Urinary Tract Dilation system) had
      significantly different resolution times for hydronephrosis (p <0.001).
      Counseling families regarding time to resolution of prenatal hydronephrosis
      should remain the same whether using Society for Fetal Urology or Urinary Tract
      Dilation grading system.

PMID- 29199000
TI  - Research Needs to Understand Self-Management of Lower Urinary Tract Symptoms:
      Summary of NIDDK Workshop.

PMID- 29199001
TI  - Microvascular complications in Nuuk, Greenland, among Greenlanders and non
      Greenlanders diagnosed with type 2 diabetes.
AB  - AIM: The objective of this study was to estimate and compare between Greenlanders
      and non-Greenlanders living in Nuuk the proportion of patients with type 2
      diabetes with microvascular complications. METHODS: This study was performed as a
      cross-sectional register study based on information in the Electronic Medical
      Record (EMR). All patients diagnosed with type 2 diabetes and with permanent
      addresses in Nuuk were included. Patients born in Greenland were considered to be
      Greenlanders, while patients born outside Greenland were considered as non
      Greenlanders. Proportions of patients with retinopathy, microalbuminuria,
      nephropathy and neuropathy were estimated based on information from the EMR.
      RESULTS: A total of 393 patients (295 Greenlanders and 98 non-Greenlanders) were
      included. In total 83.0% of all patients have been screened for retinopathy,
      while 66.4% were screened for microalbuminuria and 64.6% for neuropathy within a
      two year period. The most frequent microvascular complication was neuropathy,
      which was observed among half (49.6%) of all patients followed by
      microalbuminuria (28.4%), retinopathy (10.7%) and nephropathy (7.3%). Retinopathy
      was observed among 21.4% of the non-Greenlanders compared to only 7.0% of the
      Greenlanders (p = .001). Microalbuminuria was also observed more frequently (p =
      .047) among non-Greenlanders (37.5%) than among Greenlanders (24.9%). CONCLUSION:
      Greenlanders seem to be less prone to especially retinopathy than are non
      Greenlanders.

PMID- 29199002
TI  - Divided consumption of late-night-dinner improves glucose excursions in young
      healthy women: A randomized cross-over clinical trial.
AB  - AIMS: Our aim was to explore the acute effect of the late-night-dinner and the
      divided-dinner on postprandial glucose levels in young healthy women. METHODS:
      Fourteen women (22.6 +/- 2.6 years, BMI 20.2 +/- 1.5 kg/m2: mean +/- SD) were
      randomly assigned to this crossover study. Each participant wore a continuous
      glucose monitor for 5 days and consumed identical test meals from the second to
      the fourth day at home. Each participant consumed the test meals of breakfast at
      0800 h, lunch at 1300 h, and the half of the participants consumed dinner at 2100
      h (D21) on the second day, 1800 h (D18) on the third day, and divided dinner (DD:
      vegetable and rice at 1800 h, and vegetable and the main dish at 2100 h) on the
      fourth day. The rest of the participants consumed DD on the second day, and D21
      on the fourth day. RESULTS: D21 demonstrated higher incremental glucose peak (IGP
      2.74 +/- 0.38 vs. 1.57 +/- 0.23 mmol/L, p < .05, mean +/- SEM) and incremental
      area under the curve for glucose (IAUC) 2300-0800 h (271 +/- 63 vs. 111 +/- 37
      mmol/L * min, p < .05) than D18. On the other hand, DD ameliorated IGP (1.96 +/-
      0.29 mmol/L, p < .05), IAUC 2300-0800 h (80 +/- 29 mmol/L * min, p < .001), and
      the mean amplitude of glycemic excursion (DD 2.34 +/- 0.25 vs. D21 2.91 +/- 0.28
      mmol/L, p < .05) than D21. CONCLUSIONS: Consuming late-night-dinner increased
      postprandial glucose levels, compared to DD, suggesting DD could be a practical
      strategy for reduction of postprandial glucose levels in young healthy women.

PMID- 29199003
TI  - Implications of circulating Meteorin-like (Metrnl) level in human subjects with
      type 2 diabetes.
AB  - AIMS: Meteorin-like (Metrnl) was recently identified as a novel adipomyokine
      induced by exercise and cold exposure. Metrnl improves glucose tolerance,
      increases systemic energy expenditure, induces white adipose browning, and
      promotes anti-inflammatory gene programs in obese/diabetic mice. However, the
      relationship of Metrnl with diabetes and cardiometabolic risk variables in humans
      has not been explored. METHODS: In 800 subjects (400 patients with type 2
      diabetes and 400 non-diabetes), Metrnl concentration was measured with an enzyme
      linked immunosorbent assay, and the correlations of Metrnl level with
      anthropometric parameters, lifestyle factors, body composition values, and
      laboratory measurements were assessed. RESULTS: Metrnl concentration was
      significantly higher in patients with diabetes than in those without diabetes
      [median (inter-quartile range); diabetes: 1219.9 (1020.6, 1535.6), non-diabetes:
      1131.2 (993.1, 1313.6) pg/ml, P < .001]. After adjustment for age and sex, Metrnl
      level was significantly associated with fasting plasma glucose, blood pressure,
      lipid profile, and eGFR, but not with BMI or percent body fat. Multiple stepwise
      regression analysis exhibited that Metrnl level was independently associated with
      diabetes status (P < .001), eGFR (P < .001), and total cholesterol (P = .026) (R2
      = 0.127). In multiple logistic regression analysis, the odds ratio for the risk
      of diabetes was 3.53 (95% confidence interval: 2.04-6.10) in the highest tertile
      of Metrnl compared to the lowest after adjustment for confounding factors.
      CONCLUSIONS: This study is the first to demonstrate that Metrnl level is elevated
      in human subjects with type 2 diabetes and is inversely related to various
      cardiometabolic risk factors, including renal function.

PMID- 29199004
TI  - Dicer reprograms stromal fibroblasts to a pro-inflammatory and tumor-promoting
      phenotype in ovarian cancer.
AB  - Inflammation and host stromal activation contribute significantly to ovarian
      cancer (OC) initiation and malignant progression. However, the complex reciprocal
      interactions between them are largely unknown. Here, we discovered that the tumor
      suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma,
      and induced fibroblast activation and stromal inflammation. Dicer transformed
      normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which
      was morphologically spread out and functionally activated to fuel tumor invasion
      and metastasis. Attenuation of Dicer hampered CAF characteristics, diminished
      stromal inflammation and the role of fibroblasts in supporting tumor growth.
      Moreover, Dicer drove the expression of an "inflammatory signature" in
      fibroblasts that could be used to discriminate normal and cancerous stroma and
      predict the survival of patients with OC. Finally, the nuclear factor kappa B
      (NFkappaB) signaling was demonstrated to be responsible for Dicer effect on
      fibroblast activation and stromal inflammation, through microRNA (miR)-6780b. Our
      study represents the first report that characterizes Dicer expression and
      function in the tumor stroma, and highlights its pro-metastatic role in this
      context. Additionally, we suggest that the Dicer-miR6780b-NFkappaB cascade is an
      attractive target of choice in stroma-oriented OC therapy.

PMID- 29199005
TI  - Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of
      NF-kappaB mediated epithelial-mesenchymal transition and stemness.
AB  - Cisplatin is a first line chemotherapy in lung cancer, but decreased
      susceptibility may limit its application. In solid tumors, hypoxia alters the
      microenvironment and is associated with proliferation, metastasis, and drug
      sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly
      elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is
      extracted from ginseng and has antitumor activities. In this study, we evaluated
      if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia. We
      found that the inhibition of proliferation potential by cisplatin was reduced in
      cobalt chloride (CoCl2)-induced hypoxia in lung cancer cells. Hypoxia caused
      alterations in epithelial-mesenchymal transition (EMT), which were detected by
      cellular morphology and EMT protein markers, and in stemness analyzed by spheroid
      formation and marker molecules. Hypoxia also activated EMT, which was mediated by
      the nuclear factor kappaB (NF-kappaB) pathway, and stemness, and Rg3 inhibited
      the activation of the NF-kappaB pathway. Furthermore, Rg3 could increase the
      sensitivity to cisplatin by inhibiting EMT and stemness in hypoxic lung cancer
      cells, and this effect was confirmed in vivo. In conclusion, Rg3 may improve the
      sensitivity of cisplatin in lung cancer therapy.

PMID- 29199007
TI  - Can pulpal floor debonding be detected from occlusal surface displacement in
      composite restorations?
AB  - OBJECTIVES: Polymerization shrinkage of resin composite restorations can cause
      debonding at the tooth-restoration interface. Theory based on the mechanics of
      materials predicts that debonding at the pulpal floor would half the shrinkage
      displacement at the occlusal surface. The aim of this study is to test this
      theory and to examine the possibility of detecting subsurface resin composite
      restoration debonding by measuring the superficial shrinkage displacements.
      METHODS: A commercial dental resin composite with linear shrinkage strain of 0.8%
      was used to restore 2 groups of 5 model Class-II cavities (8-mm long, 4-mm wide
      and 4-mm deep) in aluminum blocks (8-mm thick, 10-mm wide and 14-mm tall). Group
      I had the restorations bonded to all cavity surfaces, while Group II had the
      restorations not bonded to the cavity floor to simulate debonding. One of the
      proximal surfaces of each specimen was sprayed with fine carbon powder to allow
      surface displacement measurement by Digital Image Correlation. Images of the
      speckled surface were taken before and after cure for displacement calculation.
      The experiment was simulated using finite element analysis (FEA) for comparison.
      RESULTS: Group I showed a maximum occlusal displacement of 34.7+/-6.7MUm and a
      center of contraction (COC) near the pulpal floor. Group II had a COC coinciding
      with the geometric center and showed a maximum occlusal displacement of 17.4+/
      3.8MUm. The difference between the two groups was statistically significant (p
      value=0.0007). Similar results were obtained by FEA. The theoretical shrinkage
      displacement was 44.6 and 22.3MUm for Group I and II, respectively. The lower
      experimental displacements were probably caused by slumping of the resin
      composite before cure and deformation of the adhesive layer. SIGNIFICANCE: The
      results confirmed that the occlusal shrinkage displacement of a resin composite
      restoration was reduced significantly by pulpal floor debonding. Recent in vitro
      studies seem to indicate that this reduction in shrinkage displacement could be
      detected by using the most accurate intraoral scanners currently available. Thus,
      subject to clinical validation, the occlusal displacement of a resin composite
      restoration may be used to assess its interfacial integrity.

PMID- 29199006
TI  - LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant
      meningioma cells to the therapeutic effects of radiation.
AB  - Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They
      are associated with poor outcomes due to their tendency to recur. While surgery
      and radiation (RT) are first line therapy, no effective systemic medical
      treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously
      expressed serine/threonine phosphatase involved in cell cycle regulation and DNA
      repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor
      of PP2A against AAM as a novel treatment strategy. Three human-derived
      immortalized meningioma cell lines, IOMM-LEE, GAR, and CH-157, were used to
      investigate the radio-sensitizing potential of LB-100 in AAM. Survival fraction
      by clonogenic assay, immunofluorescence, cell cycle analysis and protein
      expression were evaluated in vitro. The antitumor effects of combining LB-100
      with RT were verified in vivo by using intracranial orthotopic xenograft mouse
      model. Pharmacologic PP2A inhibition with LB-100 prior to RT enhanced the
      radiosensitivity of meningioma cells and reduced survival fraction in clonogenic
      assays. LB-100 increased DNA double-strand breakage (measured by gamma-H2AX),
      mitotic catastrophe cell death, and G2/M cell cycle arrest in irradiated
      meningioma cells. Also, LB-100 decreased activation of STAT3 and expression of
      its downstream proteins. In vivo, LB-100 and RT combined treatment prolonged the
      survival of mice with xenografts compared to RT alone. Taken together, these
      results provide convincing preclinical data to support the use of LB-100 as a
      radiosensitizing agent for treatment of malignant meningioma. Its potential for
      clinical application deserves further investigation.

PMID- 29199008
TI  - Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental
      curing light for regenerative dentistry.
AB  - : Photopolymerized hydrogels, such as gelatin methacryloyl (GelMA), have
      desirable biological and mechanical characteristics for a range of tissue
      engineering applications. OBJECTIVE: This study aimed to optimize a new method to
      photopolymerize GelMA using a dental curing light (DL). METHODS: Lithium
      acylphosphinate photo-initiator (LAP, 0.05, 0.067, 0.1% w/v) was evaluated for
      its ability to polymerize GelMA hydrogel precursors (10% w/v) encapsulated with
      odontoblast-like cells (OD21). Different irradiances (1650, 2300 and 3700mW/cm2)
      and photo-curing times (5-20s) were tested, and compared against the parameters
      typically used in UV light photopolymerization (45mW/cm2, 0.1% w/v Irgacure 2959
      as photoinitiator). Physical and mechanical properties of the photopolymerized
      GelMA hydrogels were determined. Cell viability was assessed using a live and
      dead assay kit. RESULTS: Comparing DL and UV polymerization methods, the DL
      method photopolymerized GelMA precursor faster and presented larger pore size
      than the UV polymerization method. The live and dead assay showed more than 80%
      of cells were viable when hydrogels were photopolymerized with the different DL
      irradiances. However, the cell viability decreased when the exposure time was
      increased to 20s using the 1650mW/cm2 intensity, and when the LAP concentration
      was increased from 0.05 to 0.1%. Both DL and UV photocrosslinked hydrogels
      supported a high percentage of cell viability and enabled fabrication of
      micropatterns using a photolithography microfabrication technique. SIGNIFICANCE:
      The proposed method to photopolymerize GelMA cell-laden hydrogels using a dental
      curing light is effective and represents an important step towards the
      establishment of chair-side procedures in regenerative dentistry.

PMID- 29199009
TI  - Characterization, mechanistic analysis and improving the properties of denture
      adhesives.
AB  - OBJECTIVE: Denture adhesives are widely used to avoid the detachment and sliding
      of dentures. However, the adhesion properties can be affected by variation in
      mouth conditions such as the level of salivation. The objective of this study was
      to understand the effect of environmental conditions on the adhesion properties
      of a commercially available denture adhesive named as Poligrip(r) Free
      manufactured by GlaxoSmithKline Ltd., UK and to identify the reasons for the
      observed variation in its adhesion strength. METHODS: The failure mechanisms of
      denture adhesive have been assessed through using different physical, mechanical
      and thermal characterization experiments. All methods were used in different pH,
      temperatures, and salivation conditions and at the end, a strategy was proposed
      to overcome the failure of the paste in hyposalivation as well. RESULTS: In vitro
      models mimicking the denture gingival interface were designed to evaluate the
      adhesion properties of the investigated adhesive. Changes in the adhesion
      strength in response to three major factors related to the oral conditions
      including level of salivation, pH, and temperature were measured. The results of
      lap shear, tensile test, and internal interactions suggested a cohesion failure,
      where the lowest adhesion strength was due to hyposalivation. Fourier transform
      infrared spectroscopy (FTIR) and rheological analysis confirmed the importance of
      hydrogen bonds and hydration in the adhesion strength of the paste. SIGNIFICANCE:
      The investigated scenarios are widely observed in patient using denture adhesives
      and the clinical reports have indicated the inconsistency in adhesion strength of
      the commercial products. After identifying the potential reasons for such
      behavior, methods such as the addition of tripropylene glycol methyl ether (TPME)
      to enhance internal hydrogen bonds between the polymers are proposed to improve
      adhesion in the hyposalivation scenario.

PMID- 29199010
TI  - Efficacy and Safety of Low-Dose Iodine Plaque Brachytherapy for Juxtapapillary
      Choroidal Melanoma.
AB  - PURPOSE: To evaluate low- vs high-dose plaque brachytherapy for juxtapapillary
      choroidal melanoma. DESIGN: Retrospective interventional case series. METHODS:
      Setting: Single institution. STUDY POPULATION: Forty-seven patients with
      juxtapapillary choroidal melanoma. INTERVENTION: Iodine-125 plaque brachytherapy.
      Eyes were divided into apex low-dose (LD) and high-dose (HD) groups (<= or >
      median apex dose 84.35 Gy). Main outcome measures were time to distant failure,
      local failure, death, enucleation, radiation retinopathy, optic neuropathy, and
      best-corrected visual acuity (BCVA). RESULTS: Freedom from distant failure rates
      were 96% and 95% in apex LD and HD groups at 5 years and 77% and 95% at 10 years,
      respectively (P = .84). Freedom from local failure rates were 90% in the apex LD
      group vs 89% in the HD group at 5 and 10 years (P = .96). Apex LD and HD groups
      did not differ for time to death or enucleation. Five- and 10-year freedom from
      radiation retinopathy and optic neuropathy rates were higher in the apex LD than
      HD group. Loss of >=3 BCVA lines, final BCVA 20/40 or better, and final BCVA
      20/200 or worse were more favorable in the 5 mm LD compared to HD group. Visual
      acuity outcomes did not differ between apex LD and HD groups. CONCLUSIONS: Low
      dose iodine-125 plaque brachytherapy (67.5-81 Gy at tumor apex) provides safe and
      effective tumor control for juxtapapillary choroidal melanoma and may be
      associated with reduced radiation toxicity. Larger trials are needed to determine
      the optimal therapeutic dose for juxtapapillary choroidal melanoma.

PMID- 29199011
TI  - Long-term Outcome of Second Ahmed Valves in Adult Glaucoma.
AB  - PURPOSE: To evaluate the long-term outcomes of second Ahmed glaucoma valve (AGV)
      implants in eyes with glaucoma. DESIGN: Retrospective interventional case series.
      METHODS: Patients with sequential second Ahmed valves implanted in the same eye
      from 1994 to 2016 were included. Success was defined with 3 criteria: (1)
      intraocular pressure (IOP) <= 21 mm Hg and IOP reduction of 20%; (2) IOP <= 18 mm
      Hg and IOP reduction of 25%; and (3) IOP <=15 mm Hg and IOP reduction of 30%. The
      primary analysis was the 5-year Kaplan-Meier survival rate for each criterion.
      Failure was established when the success criterion was not met at 2 consecutive
      visits at least 3 months after the surgery. Loss of light perception, requirement
      for additional glaucoma surgery, hypotony maculopathy, and serious complications
      were also considered failures. RESULTS: One hundred ten eyes from 104 patients
      were included with a mean follow-up of 5.0 years (interquartile range [IQR] 1.6
      7.33 years). The median (IQR) age at the second AGV was 68.0 (53.5-77.9) years.
      The median (IQR) time between surgeries was 2.1 (0.7-4.0) years. The 5-year
      Kaplan-Meier survival rates were 57%, 51%, and 30% for criteria 1, 2, and 3,
      respectively. CONCLUSION: A second AGV is effective in reducing IOP in patients
      who require additional IOP lowering after a first AGV. The success rates are
      comparable to primary AGV implantation, and to trabeculectomy in eyes with a
      previously implanted glaucoma drainage device. A second AGV is a viable option in
      eyes with inadequate IOP levels after a primary AGV.

PMID- 29199012
TI  - Choroidal Changes After Suprachoroidal Injection of Triamcinolone Acetonide in
      Eyes With Macular Edema Secondary to Retinal Vein Occlusion.
AB  - PURPOSE: To evaluate choroidal and suprachoroidal changes following
      suprachoroidal injection of triamcinolone acetonide injectable suspension (CLS
      TA), in eyes with macular edema due to retinal vein occlusion (RVO). DESIGN:
      Prospective cohort study within a randomized, controlled phase 2 clinical trial.
      METHODS: Enhanced depth imaging optical coherence tomography (EDI-OCT) images
      were analyzed from 38 eyes of 38 treatment-naive patients with macular edema due
      to RVO, enrolled in the prospective Suprachoroidal Injection of Triamcinolone
      Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema Due to
      Retinal Vein Occlusion (TANZANITE) study who received either a suprachoroidal
      injection of CLS-TA with an intravitreal injection of aflibercept (combination
      arm) or only an intravitreal injection of aflibercept (monotherapy arm), followed
      by monthly intravitreal aflibercept injections in both arms based on pro re nata
      criteria. RESULTS: Macular choroidal thickness measured to the outer choroidal
      vessel lumen (vascular choroidal thickness, VCT), outer choroid stroma (stromal
      choroidal thickness, SCT), or inner scleral border (total choroidal thickness,
      TCT) showed no significant changes over 3 months in both study arms (P = .231
      .342). Eyes that received combination therapy showed a trend toward thickening of
      the suprachoroidal space (SCS) compared with monotherapy alone (13.4 MUm vs 5.3
      MUm at 3 months; P = .077). In the 15 eyes that demonstrated a visible SCS at
      baseline, the SCS expanded significantly after suprachoroidal CLS-TA injection
      (16.2 MUm to 27.8 MUm at 3 months; P = .033). CONCLUSIONS: Suprachoroidal
      injection of CLS-TA does not alter choroidal thickness in eyes with macular edema
      due to RVO, but may result in expansion of the SCS.

PMID- 29199013
TI  - Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to
      Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP
      Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).
AB  - PURPOSE: To evaluate the efficacy and ocular and systemic safety of netarsudil
      0.02% ophthalmic solution, a rho-kinase inhibitor and norepinephrine transporter
      inhibitor, in patients with open-angle glaucoma and ocular hypertension. DESIGN:
      Double-masked, randomized noninferiority clinical trials: Rho Kinase Elevated IOP
      Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). METHODS: After a washout of all
      pre-study ocular hypotensive medications, eligible patients were randomized to
      receive netarsudil 0.02% once daily (q.d.), timolol 0.5% twice a day (b.i.d.),
      and (ROCKET-2 only) netarsudil 0.02% b.i.d. Data through 3 months from both
      studies are provided in this report. RESULTS: Enrolled into the 2 studies were
      1167 patients. Treatment with netarsudil q.d. produced clinically and
      statistically significant reductions from baseline intraocular pressure (P <
      .001), and was noninferior to timolol in the per-protocol population with maximum
      baseline IOP < 25 mm Hg in both studies (ROCKET-2, primary outcome measure and
      population, ROCKET-1, post hoc outcome measure). Netarsudil b.i.d. was also
      noninferior to timolol (ROCKET-2). The most frequent adverse event was
      conjunctival hyperemia, the incidence of which ranged from 50% (126/251, ROCKET
      2) to 53% (108/203, ROCKET-1) for netarsudil q.d., 59% (149/253, ROCKET-2) for
      netarsudil b.i.d., and 8% (17/208, ROCKET-1) to 11% (27/251, ROCKET-2) for
      timolol (P < .0001 for netarsudil vs timolol). CONCLUSIONS: In 2 large,
      randomized, double-masked trials reported here, once-daily dosing of netarsudil
      0.02% was found to be effective and well tolerated for the treatment of patients
      with ocular hypertension and open-angle glaucoma. The novel pharmacology and
      aqueous humor dynamic effects of this molecule suggest it may be a useful
      addition to the armamentarium of ocular hypotensive medications.

PMID- 29199015
TI  - Contemporary prognostic indicators for prostate cancer incorporating
      International Society of Urological Pathology recommendations.
AB  - Prognostic assessment is a key element in the management of patients with
      prostate cancer as it informs both treatment, follow-up and outcome prediction.
      Tumour grade should be based upon the novel and evidence-based recommendations of
      the International Society of Urological Pathology (ISUP) Consensus Conference of
      2014, with ISUP grades 1-5 being derived from 2005 ISUP modified Gleason grading,
      i.e., ISUP grade 1 (3 + 3 = 6), grade 2 (3 + 4 = 7), grade 3 (4 + 3 = 7), grade 4
      (3 + 5 = 8, 5 + 3 = 8, 4 + 4 = 8), and grade 5 (4 + 5 = 9 5 + 4 = 9, 5 + 5 = 10).
      Reporting the percentage of pattern 4 present is somewhat controversial. It does
      appear to have value for cases of ISUP grade 2 tumours where only small volumes
      of pattern 4 tumour are present, as this may assist in determining if a patient
      is appropriate for active surveillance. It is currently recommended that pure
      intraductal carcinoma (IDCP) not be graded. Here we here propose that atypical
      intraductal proliferation, indeterminate for high-grade prostatic intraepithelial
      neoplasia (PIN) and IDCP, should be reported as atypical proliferation suspicious
      for IDCP (ASID) with a note that the lesion is non-diagnostic. Pathological
      staging is dependent on tumour spread with the key factors being tumour volume,
      tumour extent including extraprostatic extension (focal and established), as well
      as seminal vesicle and pelvic lymph node involvement. Perineural infiltration in
      needle biopsies and lymphovascular invasion are evolving parameters that should
      be included in the pathology report. The identification of prognostic biomarkers
      is in evolution although a variety of transcription signatures have been shown to
      have utility in outcome assessment. Other molecular markers showing promise as
      prognostic indicators are PTEN, androgen receptors, PARP and tumour promoter (GST
      pi, RASSF1, PITX2) methylation.

PMID- 29199014
TI  - MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for
      therapeutic intervention.
AB  - The Ras family of GTPases is involved in cell proliferation, cell survival, and
      angiogenesis. It is upregulated in several cancers, including pancreatic cancer
      (PC) and leads to uncontrolled growth and aggressiveness. PC is well known to be
      a lethal disease with poor prognosis, plagued by limited therapeutic modalities.
      MicroRNAs (miRNAs), which are short non-coding RNA molecules, have recently
      emerged as regulators of signaling networks and have shown potential to target
      pathway components for therapeutic use in several malignancies. K-Ras mutations
      are widespread in PC cases (90%), with mutations detectable as early as
      pancreatic intraepithelial neoplasias and in later metastatic stages alike;
      therefore, these mutations in K-Ras are obvious drivers and potential targets for
      PC therapy. Several K-Ras targeting miRNAs have lately been discovered, and many
      of them have shown promise in combating pancreatic tumor growth in vitro and in
      mouse models. However, the field of miRNA therapy is still in its infancy, and
      miRNA mimics or anti-miRNA oligonucleotides that target Ras pathway have thus far
      not been evaluated in PC patients. In this review, we summarize the role of
      several miRNAs that regulate oncogenic K-Ras signaling in PC, with their
      prospective roles as therapeutic agents for targeting K-Ras pathway.

PMID- 29199016
TI  - Microvascular disease during pregnancy in type 1 diabetes is associated with
      ambulatory arterial stiffness.
AB  - OBJECTIVES: The objective of this study was to evaluate the association between
      the ambulatory arterial stiffness index (AASI) and markers of microvascular
      disease during pregnancy in women with type 1 diabetes. STUDY DESIGN: A total of
      151 women with type 1 diabetes mellitus were recruited for repeat 24-h BP
      recordings thrice during pregnancy and once three months post partum. Fifty women
      without diabetes served as controls. The AASI and pulse pressure (PP) were
      computed from blood pressure recordings. Repeated measures analysis of variance
      was used for comparison between groups during and after pregnancy. Linear
      regression analysis was performed with AASI and PP as dependent variables and
      albuminuria and retinopathy as independent variables. MAIN OUTCOME MEASURES: AASI
      during diabetic pregnancy and association with microvascular disease. RESULTS:
      Micro- or macroalbuminuria was present in 23% of the women and 58% had either
      simplex or proliferative retinopathy. The AASI was inversely associated with the
      coefficient of determination, which means that the stiffer vascular wall the more
      random variability in BP. CONCLUSION: AASI showed a strong association with
      microvascular disease during pregnancy in women with type 1 diabetes. Together
      with the flattened circadian rhythm this indicates a pregnancy-related functional
      change in the vascular bed.

PMID- 29199017
TI  - Linear Integration of ERK Activity Predominates over Persistence Detection in Fra
      1 Regulation.
AB  - ERK signaling regulates the expression of target genes, but it is unclear how ERK
      activity dynamics are interpreted. Here, we investigate this question using
      simultaneous, live, single-cell imaging of two ERK activity reporters and
      expression of Fra-1, a target gene controlling epithelial cell identity. We find
      that Fra-1 is expressed in proportion to the amplitude and duration of ERK
      activity. In contrast to previous "persistence detector" and "selective filter"
      models in which Fra-1 expression only occurs when ERK activity persists beyond a
      threshold duration, our observations demonstrate that the network regulating Fra
      1 expression integrates total ERK activity and responds to it linearly. However,
      exploration of a generalized mathematical model of the Fra-1 coherent feedforward
      loop demonstrates that it can perform either linear integration or persistence
      detection, depending on the basal mRNA production rate and protein production
      delays. Our data indicate that significant basal expression and short delays
      cause Fra-1 to respond linearly to integrated ERK activity.

PMID- 29199018
TI  - Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and
      Supercomplexes in Heart Tissue.
AB  - While modern structural biology technologies have greatly expanded the size and
      type of protein complexes that can now be studied, the ability to derive large
      scale structural information on proteins and complexes as they exist within
      tissues is practically nonexistent. Here, we demonstrate the application of
      crosslinking mass spectrometry to identify protein structural features and
      interactions in tissue samples, providing systems structural biology insight into
      protein complexes as they exist in the mouse heart. This includes insights into
      multiple conformational states of sarcomere proteins, as well as interactions
      among OXPHOS complexes indicative of supercomplex assembly. The extension of
      crosslinking mass spectrometry analysis into the realm of tissues opens the door
      to increasing our understanding of protein structures and interactions within the
      context of the greater biological system.

PMID- 29199019
TI  - Widespread Rewiring of Genetic Networks upon Cancer Signaling Pathway Activation.
AB  - Cellular signaling networks coordinate physiological processes in all
      multicellular organisms. Within networks, modules switch their function to
      control signaling activity in response to the cellular context. However,
      systematic approaches to map the interplay of such modules have been lacking.
      Here, we generated a context-dependent genetic interaction network of a
      metazoan's signaling pathway. Using Wnt signaling in Drosophila as a model, we
      measured >290,000 double perturbations of the pathway in a baseline state, after
      activation by Wnt ligand or after loss of the tumor suppressor APC. We found that
      genetic interactions within the Wnt network globally rewired after pathway
      activation. We derived between-state networks that showed how genes changed their
      function between state-specific networks. This related pathway inhibitors across
      states and identified genes required for pathway activation. For instance, we
      predicted and confirmed the ER-resident protein Catsup to be required for ligand
      mediated Wnt signaling activation. Together, state-dependent and between-state
      genetic interaction networks identify responsive functional modules that control
      cellular pathways.

PMID- 29199021
TI  - An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function.
AB  - Identifying genetic and environmental factors that impact complex traits and
      common diseases is a high biomedical priority. Here, we developed, validated, and
      implemented a series of multi-layered systems approaches, including (expression
      based) phenome-wide association, transcriptome-/proteome-wide association, and
      (reverse-) mediation analysis, in an open-access web server (systems
      genetics.org) to expedite the systems dissection of gene function. We applied
      these approaches to multi-omics datasets from the BXD mouse genetic reference
      population, and identified and validated associations between genes and clinical
      and molecular phenotypes, including previously unreported links between Rpl26 and
      body weight, and Cpt1a and lipid metabolism. Furthermore, through mediation and
      reverse-mediation analysis we established regulatory relations between genes,
      such as the co-regulation of BCKDHA and BCKDHB protein levels, and identified
      targets of transcription factors E2F6, ZFP277, and ZKSCAN1. Our multifaceted
      toolkit enabled the identification of gene-gene and gene-phenotype links that are
      robust and that translate well across populations and species, and can be
      universally applied to any populations with multi-omics datasets.

PMID- 29199022
TI  - CTCF-Mediated Chromatin Loops between Promoter and Gene Body Regulate Alternative
      Splicing across Individuals.
AB  - The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts
      that alter the three-dimensional architecture of chromatin, but how the presence
      of CTCF influences nearby gene expression is still poorly understood. Here, we
      analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C
      data, together with genotypes from a healthy human cohort, and measure
      statistical associations between inter-individual variability in CTCF binding and
      alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between
      promoters and intragenic regions are prevalent and that when exons are in
      physical proximity with their promoters, CTCF binding correlates with exon
      inclusion in spliced mRNA. Genome-wide, CTCF-bound exons are enriched for genes
      involved in signaling and cellular stress-response pathways. Structural analysis
      of three specific examples, checkpoint kinase 2 (CHK2), CDC-like kinase 3 (CLK3),
      and euchromatic histone-lysine N-methyltransferase (EHMT1), suggests that CTCF
      mediated exon inclusion is likely to downregulate enzyme activity by disrupting
      annotated protein domains. In total, our study suggests that alternative exon
      usage is regulated by CTCF-dependent chromatin structure.

PMID- 29199023
TI  - The Current Status and Future Role of the Phosphoinositide 3 Kinase/AKT Signaling
      Pathway in Urothelial Cancer: An Old Pathway in the New Immunotherapy Era.
AB  - The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of
      rapamycin (mTOR) pathway is a well studied signaling pathway that regulates
      diverse cellular functions including proliferation, metabolism, and
      transcription. Aberrant activation of this pathway has been implicated in
      multiple cancers. Genomic studies have shown that activating mutations in
      oncogenes as well as inactivating mutations in tumor suppressor genes are present
      across a variety of malignancies, including urothelial carcinoma. In bladder
      cancer, up to 40% of tumors exhibit constitutive activation of the PI3K/AKT/mTOR
      pathway. Current treatments for non-muscle-invasive disease confer a 5-year
      cancer-specific survival rate as high as 90%. However, patients with muscle
      invasive, recurrent, or metastatic disease have a poor prognosis. Although the
      introduction of immune checkpoint inhibitors is certainly changing the
      therapeutic landscape and is a great addition to the platinum-based therapy that
      was the standard of care for the past 3 decades, it is anticipated that a great
      number of patients would fail to respond or their disease would progress with
      either chemotherapy or immunotherapy. Therefore, the use of agents that target
      members of the PI3K/AKT/mTOR pathway represent an attractive, alternative
      therapeutic strategy for patients with advanced urothelial carcinoma. In this
      review we describe the pathway, with a focus on the rationale for targeting the
      PI3K/AKT/mTOR pathway in patients with advanced urothelial carcinoma and
      considers the challenges that we face from the current clinical trials. Novel
      agents such as PI3K inhibitors and microRNA inhibitors that target this pathway
      might lead to durable responses especially when used in combination with
      chemotherapy or immune checkpoint inhibitors, however, toxicity remains an
      obstacle. Finally, in this review we discuss the importance of developing
      biomarkers to help select appropriate patients and identify optimal treatment
      options.

PMID- 29199024
TI  - The Current State of Predicting Response on Bacillus Calmette-Guerin Treatment
      for Nonmuscle Invasive Bladder Cancer is Not Yet Useful for Patients but
      Attributes to Understanding Its Mechanisms of Action.

PMID- 29199025
TI  - Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a
      Publication Bias?

PMID- 29199026
TI  - Citation for the 2016 BAOMS Surgery Prize - Kathleen Fan.

PMID- 29199027
TI  - 10 patients, 10 years - Long term follow-up of cardiovascular risk factors in
      Glut1 deficiency treated with ketogenic diet therapies: A prospective,
      multicenter case series.
AB  - BACKGROUND AND AIMS: Glut1 Deficiency (Glut1D) is caused by impaired glucose
      transport into brain. The resulting epileptic encephalopathy and movement
      disorders can be treated effectively by high-fat carbohydrate-restricted
      ketogenic diet therapies (KDT) mimicking fasting and providing ketones as an
      alternative cerebral fuel. Recently 6-24 months follow-ups of epileptic patients
      reported elevated blood lipids and intima thickening of the carotid artery
      raising concerns about potential cardiovascular risks by KDT. To clarify
      potential cardiovascular risks we performed a prospective 10 year follow up of 10
      Glut1D patients. METHODS: Between August 2001 and January 2016 we enrolled Glut1D
      patients on KDT at two hospitals in Germany in this prospective, multicenter case
      series. The minimal follow up was 10 years. Standard deviation scores (SDS) of
      body mass index (BMI), total cholesterol (TC), HDL-/LDL cholesterol, and
      triglycerides (TG) before initiation of KDT were compared with respective values
      at 6 months, 2, 5 years, and 10 years after initiation. After 10 years on KDT
      cardiovascular risk, assessed by BMI, carotid intima-media thickness (CIMT)
      measurement, and blood pressure, was compared to a healthy reference population
      (n = 550). RESULTS: Baseline and 10 year follow-up investigations were available
      for 10 individuals with Glut1D on KDT. After two years on KDT BMI increased
      significantly, while total cholesterol, HDL-cholesterol, and LDL-cholesterol
      decreased. Within 3-5 years on KDT these differences disappeared, and after 10
      years blood lipid parameters reflected the situation at initiation of KDT. Prior
      to KDT one child had dyslipidaemia, but no child after 10 years on KDT. No
      significant differences were observed with respect to BMI SDS (p = 0.26), CIMT (p
      = 0.63) or systolic and diastolic blood pressure (SDS p = 0.11 and p = 0.37,
      respectively) in Glut1D children treated with KDT for at least 10 years compared
      to healthy controls. CONCLUSIONS: In contrast to previous short-term reports on
      adverse effects of KDT, 10-year follow-up did not identify cardiovascular risks
      of dietary treatment for Glut1D.

PMID- 29199020
TI  - The Library of Integrated Network-Based Cellular Signatures NIH Program: System
      Level Cataloging of Human Cells Response to Perturbations.
AB  - The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH
      Common Fund program that catalogs how human cells globally respond to chemical,
      genetic, and disease perturbations. Resources generated by LINCS include
      experimental and computational methods, visualization tools, molecular and
      imaging data, and signatures. By assembling an integrated picture of the range of
      responses of human cells exposed to many perturbations, the LINCS program aims to
      better understand human disease and to advance the development of new therapies.
      Perturbations under study include drugs, genetic perturbations, tissue micro
      environments, antibodies, and disease-causing mutations. Responses to
      perturbations are measured by transcript profiling, mass spectrometry, cell
      imaging, and biochemical methods, among other assays. The LINCS program focuses
      on cellular physiology shared among tissues and cell types relevant to an array
      of diseases, including cancer, heart disease, and neurodegenerative disorders.
      This Perspective describes LINCS technologies, datasets, tools, and approaches to
      data accessibility and reusability.

PMID- 29199029
TI  - The effect of customization and use of a fetal growth standard on the association
      between birthweight percentile and adverse perinatal outcome.
AB  - BACKGROUND: It has been proposed that correction of offspring weight percentiles
      (customization) might improve the prediction of adverse pregnancy outcome;
      however, the approach is not accepted universally. A complication in the
      interpretation of the data is that the main method for calculation of customized
      percentiles uses a fetal growth standard, and multiple analyses have compared the
      results with birthweight-based standards. OBJECTIVES: First, we aimed to
      determine whether women who deliver small-for-gestational-age infants using a
      customized standard differed from other women. Second, we aimed to compare the
      association between birthweight percentile and adverse outcome using 3 different
      methods for percentile calculation: (1) a noncustomized actual birthweight
      standard, (2) a noncustomized fetal growth standard, and (3) a fully customized
      fetal growth standard. STUDY DESIGN: We analyzed data from the Pregnancy Outcome
      Prediction study, a prospective cohort study of nulliparous women who delivered
      in Cambridge, UK, between 2008 and 2013. We used a composite adverse outcome,
      namely, perinatal morbidity or preeclampsia. Receiver operating characteristic
      curve analysis was used to compare the 3 methods of calculating birthweight
      percentiles in relation to the composite adverse outcome. RESULTS: We confirmed
      previous observations that delivering an infant who was small for gestational age
      (<10th percentile) with the use of a fully customized fetal growth standard but
      who was appropriate for gestational age with the use of a noncustomized actual
      birthweight standard was associated with higher rates of adverse outcomes.
      However, we also observed that the mothers of these infants were 3-4 times more
      likely to be obese and to deliver preterm. When we compared the risk of adverse
      outcome from logistic regression models that were fitted to the birthweight
      percentiles that were derived by each of the 3 predefined methods, the areas
      under the receiver operating characteristic curves were similar for all 3
      methods: 0.56 (95% confidence interval, 0.54-0.59) fully customized, 0.56 (95%
      confidence interval, 0.53-0.59) noncustomized fetal weight standard, and 0.55
      (95% confidence interval, 0.53-0.58) noncustomized actual birthweight standard.
      When we classified the top 5% of predicted risk as high risk, the methods that
      used a fetal growth standard showed attenuation after adjustment for gestational
      age, whereas the birthweight standard did not. Further adjustment for the
      maternal characteristics, which included weight, attenuated the association with
      the customized standard, but not the other 2 methods. The associations after full
      adjustment were similar when we compared the 3 approaches. CONCLUSION: The
      independent association between birthweight percentile and adverse outcome was
      similar when we compared actual birthweight standards and fetal growth standards
      and compared customized and noncustomized standards. Use of fetal weight
      standards and customized percentiles for maternal characteristics could lead to
      stronger associations with adverse outcome through confounding by preterm birth
      and maternal obesity.

PMID- 29199028
TI  - Sex-dependent influences of morphine and its metabolites on pain sensitivity in
      the rat.
AB  - Preclinical studies report that the effective dose for morphine is approximately
      2-fold higher in females than males. Following systemic administration, morphine
      is metabolized via Phase II glucuronidation in the liver and brain into two
      active metabolites: morphine-3-glucuronide (M3G) and morphine-6-glucuronide
      (M6G), each possessing distinct pharmacological profiles. M6G binds to MU opioid
      receptors and acts as a potent analgesic. In contrast, M3G binds to toll-like
      receptor 4 (TLR4), initiating a neuroinflammatory response that directly opposes
      the analgesic effects of morphine and M6G. M3G serum concentrations are 2-fold
      higher in females than males, however, sex-specific effects of morphine
      metabolites on analgesia and glial activation in vivo remain unknown. The present
      studies test the hypothesis that increased M3G, and subsequent TLR4-mediated
      activation of glia, is a primary mechanism driving the attenuated response to
      morphine in females. We demonstrate that intra-PAG M6G results in a greater
      analgesic response in females than morphine alone. M6G analgesia was reversed
      with co-administration of (-)-naloxone, but not (+)-naloxone, suggesting that
      this effect is MU opioid receptor mediated. In contrast, intra-PAG administration
      of M3G significantly attenuated the analgesic effects of systemic morphine in
      males only, increasing the 50% effective dose of morphine two-fold (5.0 vs
      10.3mg/kg) and eliminating the previously observed sex difference. An increase in
      IL-1beta, IL-6 and TNF was observed in females following intra-PAG morphine or
      M6G. In males, only IL-1beta levels increased following morphine. Changes in
      cytokine levels following M3G were limited to TNF in females. Together, these
      data implicate sex differences in morphine metabolism, specifically M3G, as a
      contributing factor in the attenuated response to morphine observed in females.

PMID- 29199030
TI  - Effect of a single early EEG neurofeedback training on remediation of spatial
      neglect in the acute phase.

PMID- 29199031
TI  - Surgical success and lateral incomitance following three-muscle surgery for large
      angle horizontal strabismus.
AB  - PURPOSE: To evaluate motor alignment, motility, and sensorial outcomes of
      simultaneous three-muscle surgery for large-angle horizontal strabismus, with
      special attention to lateral incomitance and long-term success. METHODS: The
      medical records of consecutive patients with large-angle deviations (>=30Delta)
      who underwent simultaneous surgery on three horizontal muscles to correct
      esotropia or exotropia were reviewed retrospectively. Successful motor alignment
      was defined as residual deviation of <=10Delta and consecutive deviation in
      primary position of <=4Delta, with no induced lateral incomitance >5Delta between
      lateral gazes. Sensory success was defined as an improvement in stereopsis of >=2
      octaves. Surgical procedures included a combination of recessions and
      resections/plications depending on surgeon preference. The majority of cases were
      two-muscle recessions combined with one-muscle resection or plication. RESULTS: A
      total of 19 patients with exotropia and 9 patients with esotropia were included.
      In the esotropic group, the mean age at surgery was 48 +/- 15 years and the mean
      preoperative deviation improved from 45.6Delta +/- 11.9Delta to 1.5Delta +/-
      1.6Delta (P < 0.001); there was no undercorrection, recurrence or overcorrection.
      In the exotropic group, the mean age at surgery was 44 +/- 25 years, and the mean
      preoperative deviation improved from 44.1Delta +/- 8.7Delta to 5.8Delta +/-
      9.6Delta (P < 0.001), recurrence occurred in 2 (22%). Overall motor success at
      distance was 85%, with 1 (3.8%) unsuccessful patient due to induced incomitance.
      Sensory success was 44% for esotropia and 31% for exotropia. No patient lost
      stereopsis. CONCLUSIONS: Patients undergoing three-muscle surgery for horizontal
      strabismus had good motor outcomes with low incidence of induced lateral
      incomitance. Motor and sensorial outcomes for esotropia were very stable.

PMID- 29199032
TI  - Surgical outcome of superior rectus transposition in esotropic Duane syndrome and
      abducens nerve palsy.
AB  - PURPOSE: To evaluate surgical outcome of superior rectus transposition (SRT) in
      esotropic Duane syndrome (DS) and abducens nerve palsy. METHODS: Retrospective
      medical record analysis of all patients with esotropic DS and abducens nerve
      palsy treated with SRT at our center with minimum follow-up of 6 months. Primary
      outcome measures were esotropia in primary position and abduction limitation.
      Secondary outcome measures included head turn, stereopsis, and cyclovertical
      deviations. RESULTS: A total of 20 eyes of 19 patients were included: 9 with DS
      and 10 with traumatic abducens nerve palsy. One patient had bilateral esotropic
      DS. Mean age of DS patients was 12.5 +/- 10.1 years; of abducens nerve palsy
      patients, 25.4 +/- 11.3 years. Medial rectus recession (MRc) of 3.5 mm was
      additionally performed in 5 DS eyes. An adjustable MRc 5.6 +/- 2.2 mm with or
      without augmentation suture was performed in all abducens nerve palsy patients.
      In DS patients, esotropia improved from 27.5Delta +/- 5.4Delta to 3.6Delta +/-
      6.4Delta (P < 0.001), abduction limitation reduced from -3.8 to -1.8 (P < 0.001),
      and head posture improved from 20 degrees  to 4 degrees  (P < 0.001) at 6 months.
      In abducens nerve palsy patients, esotropia improved from 51.5Delta +/- 18.8Delta
      to 6.1Delta +/- 10.7Delta (P < 0.001), abduction limitation reduced from -3.8 to 
      2, and head posture improved from 25 degrees  to 8 degrees  (P < 0.001).
      Stereopsis improved in 4 patients (P = 0.12). No patient had vertical deviation
      or torsional diplopia. CONCLUSIONS: In our patient cohort with esotropic DS or
      abducens nerve palsy, SRT reduced esotropia and improved abduction. Because of a
      long-term exotropic drift, initial undercorrection in the immediate postoperative
      period may prevent eventual overcorrection.

PMID- 29199033
TI  - Psychosocial reactions to upper extremity limb salvage: A case series.
AB  - STUDY DESIGN: Case series. INTRODUCTION: A salvaged limb is one that has
      undergone a major traumatic injury, followed by repeated surgical attempts in
      order to avoid amputation. Psychological recovery for individuals with lower
      extremity limb salvage has been examined in a number of studies. However,
      psychosocial reactions for individuals with upper extremity (UE) limb salvage are
      understudied in the literature. PURPOSE OF THE STUDY: The purpose of this study
      was to explore the process of psychosocial adaptation for 3 trauma cases after UE
      limb salvage. METHODS: The Reactions to Impairment and Disability Inventory was
      used to assess psychosocial adaptation. Physical function outcomes (pain, range
      of motion, edema, sensation, and dexterity) are presented. The Disabilities of
      the Arm, Shoulder, and Hand measure was used to assess perceived disability.
      Medical and rehabilitation history are discussed for each case, in order to
      provide in-depth understanding of the impact of these injuries. RESULTS:
      Reactions to injury varied across the cases; however, outcomes suggest that
      psychosocial adaptation may be influenced by the experience of pain, the ability
      to participate in valued roles and activities, and having a supportive social
      network. DISCUSSION: For this population, therapists may consider emphasizing
      pain management, focusing on client-centered goals and interventions, and
      facilitating peer support. Providers should closely monitor patients for signs of
      poor adaptation, such as hand-hiding behaviors. CONCLUSIONS: This study is among
      the first to examine psychological outcomes for the UE limb salvage population.
      Future research would be beneficial to provide deeper understanding of the
      psychosocial challenges for these individuals.

PMID- 29199034
TI  - The Rectangle: A hand-based pattern for a dorsal short thumb opponens orthosis
      with metacarpophalangeal support.

PMID- 29199035
TI  - Changes in zinc status and zinc transporters expression in whole blood of
      patients with Systemic Inflammatory Response Syndrome (SIRS).
AB  - INTRODUCTION: Critically ill patients develop severe stress, inflammation and a
      clinical state that may raise the utilization and metabolic replacement of many
      nutrients and especially zinc, depleting their body reserves. This study was
      designed to assess the zinc status in critical care patients with systemic
      inflammatory response syndrome (SIRS), comparing them with a group of healthy
      people, and studying the association with expression of zinc transporters.
      MATERIAL AND METHODS: This investigation was a prospective, multicentre,
      comparative, observational and analytic study. Twelve critically ill patients
      from different hospitals and 12 healthy subjects from Granada, Spain, all with
      informed consent were recruited. Data on daily nutritional assessment, ICU
      severity scores, inflammation, clinical and nutritional parameters, plasma and
      blood cell zinc concentrations, and levels of transcripts for zinc transporters
      in whole blood were taken at admission and at the seventh day of the ICU stay.
      RESULTS: Zinc levels on critical ill patient are diminish comparing with the
      healthy control (HS: 0.94 +/- 0.19; CIPF: 0.67 +/- 0.16 mg/dL). The 58% of
      critical ill patients showed zinc plasma deficiency at beginning of study while
      50.0% of critical ill after 7 days of ICU stay. ZnT7, ZIP4 and ZIP9 were the zinc
      transporters with highest expression in whole blood. In general, all zinc
      transporters were significantly down-regulated (P < 0.05) in the critical ill
      population at admission in comparison with healthy subjects. Severity scores and
      inflammation were significantly associated (P < 0.05) with zinc plasma levels,
      and zinc transporters ZIP3, ZIP4, ZIP8, ZnT6, ZnT7. Expression of 11 out of 24
      zinc transporters was analysed, and ZnT1, ZnT4, ZnT5 and ZIP4, which were
      downregulated by more than 3-fold in whole blood of patients. CONCLUSION: In
      summary, in our study an alteration of zinc status was related with the severity
      of-illness scores and inflammation in critical ill patients since admission in
      ICU stay. SIRS caused a general shut-down of expression of zinc transporters in
      whole blood. That behavior was associated with severity and inflammation of
      patients at ICU admission regardless zinc status. We conclude that zinc
      transporters in blood might be useful indicators of severity of systemic
      inflammation and outcome for critically ill patients.

PMID- 29199036
TI  - Second International Conference on Crimean-Congo Hemorrhagic Fever.
AB  - The Second International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was
      held in Thessaloniki, Greece, from September 10-13, 2017, and brought together
      international public health professionals, clinicians, ecologists, and basic
      laboratory researchers. Nearly 100 participants, representing 24 countries and
      the World Health Organization (WHO), were in attendance. Meeting sessions covered
      the epidemiology of CCHF in humans; ticks and virus-tick interactions; wild and
      domestic animal hosts; molecular virology; taxonomic classification; pathogenesis
      and animal models; clinical aspects and diagnosis; clinical management and
      clinical trials; and disease prevention in humans. The concluding session focused
      on recent WHO recommendations for public health measures and future research.
      This report summarizes lectures by the invited speakers and highlights advances
      in the field.

PMID- 29199037
TI  - Potential role of lncRNAs in contributing to pathogenesis of chronic
      glomerulonephritis based on microarray data.
AB  - BACKGROUND: Chronic glomerulonephritis (CGN) is the most common form of primary
      glomerular disease with unclear molecular mechanisms, which related to immune
      mediated inflammatory diseases. Our study intended to identify potential long non
      coding RNAs (lncRNAs) and genes, and to determine the potential molecular
      mechanisms of CGN pathogenesis. METHODS: The microarray of GSE64265 and GSE46295
      were downloaded from the Gene Expression Omnibus database, GSE64265 including 3
      rats control kidney tissues and 5 rats model kidney tissues, GSE46295 including 3
      rats control kidney tissues and 3 rats model kidney tissues, which was on the
      basis of GPL1355 platform. Identification of differentially expressed lncRNAs and
      mRNAs were performed between the 2 groups. Gene ontology (GO) and pathway
      enrichment analyses were performed to analyze the biological functions and
      pathways for the differentially expressed mRNAs. LncRNA-mRNA weighted co
      expression network was constructed using the WGCNA package to analyses for the
      genes in the modules. The protein-protein interaction (PPI) network was
      visualized. RESULTS: A total of 40 significantly up-regulated and 24 down
      regulated lncRNAs, 653 up-regulated and 128 down-regulated mRNAs were identified.
      Additionally, Cdk1, with the highest connectivity degree in PPI network, was
      noteworthy enriched in cell cycle. Seven lncRNAs: NONRATT026650, LOC102547664,
      NONRATT77021989, NONRATT012453, LOC102551856, LOC102553536 and NONRATT7047175
      were observed in the modules of lncRNA-mRNA weighted co-expression network.
      CONCLUSIONS: LncRNAs NONRATT026650, LOC102547664, NONRATT77021989, NONRATT012453,
      LOC102551856, LOC102553536 and NONRATT7047175 were differentially expressed and
      might play important roles in the development of CGN. Key genes, such as Cd44,
      Rftn1, Runx1, may be crucial biomarkers for CGN.

PMID- 29199038
TI  - Association of interleukin-10 gene single nucleotide polymorphisms with
      susceptibility to systemic lupus erythematosus in a Chinese population.
AB  - The aim of this study was to investigate the association of interleukin (IL)-10
      gene single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus
      erythematosus (SLE) in a Chinese population. 848 SLE patients and 461 normal
      controls were recruited in this study. Nine SNPs in IL-10 gene (rs1518110,
      rs1518111, rs1554286, rs1800890, rs1800893, rs3024493, rs3024495, rs3024498 and
      rs6667202) were genotyped using TaqMan genotyping assays on Fluidigm 192.24
      system. The frequency of IL-10 rs3024498-C allele was significantly higher in
      patient group compared with control subjects (OR=5.118, 95% CI=1.819-14.405,
      P=0.002). No significant differences were detected for the distribution of allele
      and genotype frequencies of other eight SNPs between patients with SLE and
      controls after Bonferroni correction (all P>0.0056). Interestingly, significant
      differences were detected both in the allele and genotype frequencies of
      rs3024498 between SLE patients with and without arthritis (P=0.002, P=0.022,
      respectively).There was significant difference in genotype frequency at rs3024498
      between SLE patients with and without malar rash (P=0.040). And, there was
      significant difference in allele frequency at rs3024498 between SLE patients with
      and without anti-double-stranded DNA (P=0.032). Meanwhile, significant difference
      in genotype frequency at rs1518110 and rs1518111 were found in patients with and
      without lupus headache (P=0.025, P=0.038, respectively). There were significant
      difference in allele and genotype frequency at rs1800890 and rs6667202 between
      SLE patients with and without thrombocytopenia (rs1800890: P=0.016, P=0.026,
      respectively; rs6667202: P=0.007, P=0.007, respectively). Further, significant
      difference were observed both in allele frequency and in genotype distribution of
      rs1800893 between patients with and without tubular urine and proteinuria
      (tubular urine: P<0.001, P=0.003, respectively; proteinuria: P=0.001, P=0.018,
      respectively). In summary, IL-10 rs3024498 polymorphism might contribute to SLE
      susceptibility and several clinical phenotypes.

PMID- 29199040
TI  - Progress towards a vaccine against Ebola to meet emergency medical countermeasure
      needs.
AB  - The Ebola virus epidemic in West Africa proved to be the largest in the history
      of filovirus outbreaks, causing the World Health Organization to declare a public
      health emergency of international concern in August of 2014. In collaboration
      with domestic and international partners, the Biomedical Advanced Research and
      Development Authority (BARDA) initiated several vaccine development projects in
      support of the overall response efforts. The urgency associated with the epidemic
      triggered the clinical evaluation of lead vaccine candidates starting in late
      2014. Here we will discuss development of the lead vaccine candidates for Ebola
      virus, specifically Zaire ebolavirus.

PMID- 29199039
TI  - The coronavirus nucleocapsid protein is ADP-ribosylated.
AB  - ADP-ribosylation is a common post-translational modification, although how it
      modulates RNA virus infection is not well understood. While screening for ADP
      ribosylated proteins during coronavirus (CoV) infection, we detected a ~55kDa ADP
      ribosylated protein in mouse hepatitis virus (MHV)-infected cells and in virions,
      which we identified as the viral nucleocapsid (N) protein. The N proteins of
      porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome (SARS)
      CoV and Middle East respiratory syndrome (MERS)-CoV were also ADP-ribosylated.
      ADP-ribosylation of N protein was also observed in cells exogenously expressing N
      protein by transduction using Venezuelan equine encephalitis virus replicon
      particles (VRPs). However, plasmid-derived N protein was not ADP-ribosylated
      following transient transfection but was ADP-ribosylated after MHV infection,
      indicating that this modification requires virus infection. In conclusion, we
      have identified a novel post-translation modification of the CoV N protein that
      may play a regulatory role for this important structural protein.

PMID- 29199041
TI  - Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass
      profiles to DTaP booster vaccination.
AB  - INTRODUCTION: Duration of protection against pertussis is shorter in adolescents
      who have been immunized with acellular pertussis (aP) in infancy compared with
      adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is
      related to immune responses elicited by these priming vaccines. To better
      understand differences in vaccine induced immunity, we determined pertussis,
      diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in
      wP- and aP-primed children before and after two successive DTaP booster
      vaccinations. METHODS: Blood samples were collected in a cross-sectional study
      from wP- or aP-primed children before and 1 month after the pre-school DTaP
      booster vaccination at age 4 years. Blood samples were collected from two
      different wP- and aP-primed groups of children before, 1 month and 1 year after
      an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels
      against the antigens included in the DTaP vaccine have been determined with
      fluorescent-bead-based multiplex immunoassays. RESULTS: At 4 years of age, the
      IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine
      antigens were significantly higher in aP-primed children compared with wP-primed
      children. IgG4 concentrations further increased upon the two successive booster
      vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but
      remained significantly higher in aP-primed children. CONCLUSIONS: The pertussis
      vaccinations administered in the primary series at infancy determine the vaccine
      antigen-specific IgG subclass profiles, not only against the pertussis vaccine
      antigens, but also against the co-administered diphtheria and tetanus vaccine
      antigens. These profiles did not change after DTaP booster vaccinations later in
      childhood. The different immune response with high proportions of specific IgG4
      in some aP-primed children may contribute to a reduced protection against
      pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089.

PMID- 29199042
TI  - A novel antigenic cathepsin B protease induces protective immunity in Trichinella
      infected mice.
AB  - Trichinellosis is a foodborne disease that remains a public health hazard and an
      economic problem in food safety. Vaccines against the parasite can be an
      effective way to control this disease; however, commercial vaccines against
      Trichinella infection are not yet available. Trichinella cathepsin B proteins
      appear to be promising targets for vaccine development. Here, we reported for the
      first time the characterization of a novel cDNA that encodes Trichinella spiralis
      (T. spiralis) cathepsin B-like protease 2 gene (TsCPB2). The recombinant mature
      TsCPB2 protein was successfully expressed in E. coli system and purified with Ni
      affinity chromatography. TsCPB2 expression was detected at all the developmental
      stages of T. spiralis and it was expressed as an excretory-secretory protein of
      T. spiralis muscle larvae. Immunization with TsCPB2 antigen induced a combination
      of humoral and cellular immune responses, which manifested as a mixed Th1/Th2
      response, as well as remarkably elevated IgE level. Moreover, vaccination of mice
      with TsCPB2 that were subsequently challenged with T. spiralis larvae resulted in
      a 52.3% (P < .001) reduction in worm burden and a 51.2% (P < .001) reduction in
      muscle larval burden. Our results suggest that TsCPB2 induces protective immunity
      in Trichinella-infected mice and might be a novel vaccine candidate against
      trichinellosis.

PMID- 29199044
TI  - Intussusception hospitalizations before rotavirus vaccine introduction:
      Retrospective data from two referral hospitals in Tamil Nadu, India.
AB  - BACKGROUND: The indigenous oral rotavirus vaccine Rotavac(r) was introduced into
      the public immunization system in India in 2016 and will be expanded in phases.
      This data will describe the epidemiology of intussusception in India in absence
      of rotavirus vaccination and will help in setting up or designing a safety
      monitoring system. METHODS: Medical records of intussusception cases between 2013
      and 2016 in two major referral hospitals in Tamil Nadu, India were reviewed, and
      data on clinical presentation and management and outcome were collated. RESULTS:
      A total of 284 cases of intussusception were diagnosed and managed at the two
      centers of which 280/284 could be classified as level 1 by the Brighton criteria.
      Median age at presentation was 8 months (Inter Quartile Range, IQR 6-17.2) with a
      male to female ratio of 2.1:1. Over half (57.7%) required surgical intervention
      while the rest underwent non-surgical or conservative management. CONCLUSIONS:
      Retrospective data from referral hospitals is sufficient to classify cases of
      intussusception by the Brighton criteria. These baseline data will be useful for
      monitoring when rotavirus vaccination is introduced.

PMID- 29199043
TI  - Evaluating interest in an influenza A(H5N1) vaccine among laboratory workers who
      work with highly-pathogenic avian influenza viruses in the United States.
AB  - BACKGROUND: Highly pathogenic avian influenza A (HPAI) viruses found in poultry
      and wild birds occasionally infect humans and can cause serious disease. In 2014,
      the Advisory Committee on Immunization Practices (ACIP) reviewed data from one
      licensed ASO3-adjuvanted influenza A(H5N1) vaccine for consideration of use
      during inter-pandemic periods among persons with occupational exposure. To guide
      vaccine policy decisions, we conducted a survey of laboratory workers to assess
      demand for HPAI vaccination. METHODS: We designed an anonymous web survey
      (EpiInfo 7.0) to collect information on demographics, type of work and time spent
      with HPAI viruses, and interest in HPAI vaccination. Eligible participants were
      identified from 42 entities registered with United States Department of
      Agriculture's Agricultural Select Agent program in 2016 and emailed electronic
      surveys. Personnel with Biosafety Level 3 enhanced (BSL-3E) laboratory access
      were surveyed. Descriptive analysis was performed. RESULTS: Overall, 131
      responses were received from 33 principal investigators, 26 research scientists,
      24 technicians, 15 postdoctoral fellows, 6 students, and 27 others. The estimated
      response rate was 15% among the laboratory personnel of responding principal
      investigators. One hundred respondents reported working in a BSL-3E area where
      HPAI experiments occurred with a mean time of 5.1-11.7 h per week. Overall, 49%
      were interested in receiving an A(H5N1) vaccine. By role, interest was highest
      among students (80%) and among those who spent >50% of their time in a BSL-3E
      area (64%). Most (61%) of those who said they might be or were not interested in
      vaccine believed it would not provide additional protection to current safety
      practices. CONCLUSIONS: Half of responding laboratory workers was interested in
      receiving an influenza A(H5N1) vaccine. HPAI vaccination of laboratory workers at
      risk of occupational exposure could be used along with existing safety practices
      to protect this population.

PMID- 29199045
TI  - The mechanism of myocardial hypertrophy regulated by the interaction between mhrt
      and myocardin.
AB  - As a strong transactivator of promoters containing CarG boxes, myocardin was
      critical for the cardiac muscle program and necessary for normal cardiogenesis.
      So it probably represents a viable therapeutic biomarker in the setting of
      cardiac hypertrophy and failure. In recent years, the studies of regulation of
      cardiac hypertrophy via myocardin are so common, and the molecular mechanism is
      becoming more and more clear. Here, we have revealed a kind of interaction
      between mhrt and myocardin shown as a feedback regulatory mechanism in the
      regulation of cardiac hypertrophy. That is, the lncRNA mhrt can affect the
      acetylation of myocardin by HDAC5 to inhibit cardiac hypertrophy induced by
      myocardin. Moreover, myocardin also can directly activate the mhrt transcription
      through binding to the CarG box. Thus, mhrt and myocardin form a regulation loop
      in the process of cardiac hypertrophy. This finding may play a positive role in
      revealing the complete mechanisms of cardiac hypertrophy.

PMID- 29199046
TI  - "Open access" growth histories in millipedes (Diplopoda).
AB  - A unique pattern of missing defence glands on certain body rings is described for
      two species of the millipede family Mongoliulidae, order Julida: Ussuriiulus
      pilifer Golovatch, 1980, and Koiulus interruptus Enghoff et al., 2017. Based on
      the patterns of missing glands observed in recently collected samples of the two
      species, numbers of podous and apodous body rings in successive stadia of the
      postembryonic development can be inferred for each individual millipede, which in
      turn allows the reconstruction of pathways of anamorphosis in these species. The
      inferred numbers of body rings in developmental stadia are compared with actual
      numbers observed on additional samples, including the type series, of U. pilifer.
      The pattern of missing glands in the two mongoliulid species is compared with the
      pattern of missing glands typical of the entire millipede order Polydesmida.

PMID- 29199048
TI  - Arterial Pressure Monitoring and Site-Specific Gradient Issues During Cardiac
      Surgery.

PMID- 29199047
TI  - Egg-laying behavior and morphological and chemical characterization of egg
      surface and egg attachment glue of the digger wasp Ampulex compressa
      (Hymenoptera, Ampulicidae).
AB  - For providing their offspring females of the digger wasp species Ampulex
      compressa hunt cockroaches, paralyze them and attach as a rule one egg to the
      coxa of one of the mid legs of their prey. We observed the egg-laying behavior
      and examined with light- and scanning microscopy (i) nearly mature eggs from
      ovaries of freshly dissected females and (ii) eggs immediately after their
      deposition on the coxae of their prey. The length of the white bean-shaped eggs
      varied between 2.2 and 3.0 mm, their diameter between 0.66 and 0.72 mm, and their
      weight between 345 and 832 MUg. The surface of fresh, untreated eggs shows even
      at higher magnifications (>20.000*) a smooth appearance. However, after
      conventional fixation, dehydration with ethyl-alcohol and critical-point drying
      the egg-surface exhibited a little bit texture. The eggs are at two-third of
      their underside glued to the coxa of the prey. With the naked eye the glue
      appears as a compact mass. The eggs may be mechanically removed from the
      substrate (their attachment site); however, in doing so the viscous attachment
      glue appears in a more fibrous consistence. The polypeptide composition washed
      off the egg surface and the glue revealed no similarities, whereas the molecular
      mass of two polypeptides were similar between glue and the Dufour's gland
      contents.

PMID- 29199049
TI  - Successful Use of Serratus Plane Block as Primary Anesthetic for Video-Assisted
      Thoracoscopic Surgery (VATS)-Assisted Pleural Effusion Drainage.

PMID- 29199050
TI  - The Role of Hemoglobin A1c as a Biomarker and Risk Assessment Tool in Patients
      Undergoing Non-cardiac and Cardiac Surgical Procedures.

PMID- 29199051
TI  - Noninvasive Evaluation of Native Valvular Regurgitation: A Review of the 2017
      American Society of Echocardiography Guidelines for the Perioperative
      Echocardiographer.

PMID- 29199052
TI  - Protective Invasive Ventilation in Cardiac Surgery: A Systematic Review With a
      Focus on Acute Lung Injury in Adult Cardiac Surgical Patients.

PMID- 29199053
TI  - Post-Stroke Cancer Risk among Postmenopausal Women: The Women's Health
      Initiative.
AB  - BACKGROUND: Associations between a history of cancer and higher subsequent stroke
      risk have been established. However, whether a history of stroke is associated
      with higher subsequent cancer risk, especially for cancers with overlapping risk
      factors for stroke, is unknown. Therefore, we examined whether a history of
      stroke was associated with subsequent cancer risk and tumor site, by
      race/ethnicity, among postmenopausal women. METHODS: Using data from 145,075
      participants in the Women's Health Initiative observational study and clinical
      trials (1993-2014), we used Cox proportional hazards models to predict cancer
      risk, comparing women with and without a history of stroke. Bivariate and
      multivariate models were estimated, accounting for potential confounders and
      death as a competing risk. RESULTS: Women with a history of stroke survived
      roughly 3 fewer years than women without such history. The average time between
      incident stroke and incident cancer was 4.8 years. In adjusted competing risk
      models, women with a history of stroke had a lower cancer risk compared with
      women without such a history (adjusted hazard ratio, 0.81; 95% CI, 0.75-0.88).
      The magnitude of the association between a history of stroke and time to incident
      cancer was similar across racial/ethnic groups. DISCUSSION: Postmenopausal women
      with a history of stroke had a significantly lower risk of subsequent cancer
      compared with women with no history of stroke. Although the risk of certain
      cancers were greater for African American compared with White women, the
      association between a stroke history and cancer risk did not vary by
      race/ethnicity. CONCLUSIONS: Postmenopausal women with a history of stroke, who
      survive long enough to develop cancer, have a lower risk of cancer than women
      without such a history. Future studies should examine whether behavioral or
      clinical characteristics explain and/or mediate this association.

PMID- 29199054
TI  - A multilevel approach to modeling health inequalities at the intersection of
      multiple social identities.
AB  - RATIONALE: Examining interactions between numerous interlocking social identities
      and the systems of oppression and privilege that shape them is central to health
      inequalities research. Multilevel models are an alternative and novel approach to
      examining health inequalities at the intersection of multiple social identities.
      This approach draws attention to the heterogeneity within and between
      intersectional social strata by partitioning the total variance across two
      levels. METHOD: Utilizing a familiar empirical example from social epidemiology
      body mass index among U.S. adults (N = 32,788)-we compare the application of
      multilevel models to the conventional fixed effects approach to studying high
      dimension interactions. Researchers are often confronted with the need to explore
      numerous interactions of identities and social processes. We explore the
      interactions of five dimensions of social identity and position-gender,
      race/ethnicity, income, education, and age-for a total of 384 unique
      intersectional social strata. RESULTS: We find that the multilevel approach
      provides advantages over conventional models, including scalability for higher
      dimensions, adjustment for sample size of social strata, model parsimony, and
      ease of interpretation. CONCLUSION: Considerable variation is attributable to the
      within-strata level, indicating the low discriminatory accuracy of these
      intersectional identities and the high within-strata heterogeneity of risk that
      remains unexplained. Multilevel modeling is an innovative and valuable tool for
      evaluating the intersectionality of health inequalities.

PMID- 29199055
TI  - Bone Marrow Involvement in Malignant Lymphoma: Evaluation of Quantitative PET and
      MRI Biomarkers.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the diagnostic utility of
      standardized uptake values (SUV) and apparent diffusion coefficients (ADC) for
      assessment of focal and diffuse bone marrow involvement in patients with
      malignant lymphoma. MATERIALS AND METHODS: Sixty treatment-naive patients (28
      males; mean age 51.2 +/- 16.7 years) with histologically proven lymphoma, who
      underwent fludeoxyglucose (18F) positron emission tomography-computed tomography
      ([F18]-FDG-PET/CT) and whole-body diffusion-weighted imaging (WB-DWI) within 7
      days, and also routine bone marrow biopsy, were included in this institutional
      review board-approved, retrospective study. The maximum SUV (SUVmax) on [F18]-FDG
      PET/CT, and the mean ADC (ADCmean, *10-3 mm2/s) on whole-body-DWI, were extracted
      from focal lesions, or, in their absence, from the thoracic (Th8) and lumbar
      vertebral bodies (L4), the sacral bone (S1), and the iliac crest. Lesion-to-liver
      ratios (SUVmax-ratio) were calculated. Pearson correlation coefficients were used
      to assess the correlation between SUVmax-ratios and ADCmean values. RESULTS: Bone
      marrow involvement was observed in 16 of 60 patients (8 of 16 with diffuse
      infiltration). The SUVmax-ratio cutoff value was 95.25% for focal and 70.2% for
      diffuse bone marrow involvement (sensitivity/specificity of 87.5%/86.4% and
      100%/43.2%, respectively). The ADCmean cutoff value was 0.498 for focal and 0.401
      for diffuse bone marrow involvement (sensitivity/specificity of 100%/90.9% and
      87.5%/56.8%, respectively). No significant correlations were found between SUVmax
      ratios and ADCmean values in the different groups. CONCLUSION: With the liver as
      reference tissue, quantitative [F18]-FDG-PET/CT may be useful to differentiate
      bone marrow involvement from normal bone marrow in patients with lymphoma, even
      though the specificity for diffuse marrow involvement is rather low. Quantitative
      DWI can be used only to distinguish focal bone marrow lesions from normal bone
      marrow.

PMID- 29199056
TI  - Screening Mammography Utilization and Medicare Beneficiaries' Perceptions of
      Their Primary Care Physicians.
AB  - RATIONALE AND OBJECTIVES: To assess associations between screening mammography
      utilization and Medicare beneficiaries' relationships with, and impressions of,
      their primary care physicians. MATERIALS AND METHODS: Using the Medicare Current
      Beneficiary Survey Access to Care Public Use File, we retrospectively studied
      responses from a national random cross section of Medicare beneficiaries surveyed
      in 2013 regarding perceptions of their primary care physicians and their
      screening mammography utilization. Statistical analysis accounted for subject
      weighting factors to estimate national screening utilization. RESULTS: Among 7492
      female Medicare beneficiaries, 62.0% (95% confidence interval 59.8%-64.2%)
      underwent screening mammography. Utilization was higher for beneficiaries having
      (vs. not) a regular medical practice or clinic (63.2% vs. 34.6%) and a usual
      physician (63.8% vs. 50.3%). Utilization was higher for beneficiaries very
      satisfied (vs. very dissatisfied) with the overall quality of care they received
      (66.0% vs. 35.8%), their ease of getting to a doctor (67.7% vs. 43.2%), and their
      physician's concerns for their health (65.7% vs. 53.4%), as well as for
      beneficiaries strongly agreeing (vs. strongly disagreeing) that their physician
      is competent (66.0% vs. 54.1%), understands what is wrong (66.3% vs. 47.1%),
      answers all questions (67.0% vs. 46.7%), and fosters confidence (66.0% vs.
      50.6%). Independent predictors of screening mammography utilization (P < .05)
      were satisfaction with quality of care, having a regular practice or clinic, and
      satisfaction with ease of getting to their physician. CONCLUSIONS: Screening
      mammography utilization is higher among Medicare beneficiaries with established
      primary physician relationships, particularly when those relationships are
      favorable. To optimize screening mammography utilization, breast imagers are
      encouraged to support initiatives to enhance high-quality primary care
      relationships.

PMID- 29199057
TI  - Epidemiology of Hepatic Steatosis at a Tertiary Care Center: An MRI-based
      Analysis.
AB  - RATIONALE AND OBJECTIVES: Little is known about the frequency and risk factors of
      hepatic steatosis in the tertiary care setting. Such knowledge is essential to
      clinicians making decisions about testing for this condition. Thus, our aim was
      to describe the epidemiology of hepatic steatosis, as captured by magnetic
      resonance imaging (MRI), at a tertiary care center. MATERIALS AND METHODS: A near
      consecutive cohort of 1006 adult patients underwent standard-of-care liver MRIs.
      Images were retrospectively processed to derive proton density fat fraction
      (PDFF) maps. Data from three spatially distinct regions of interest (ROIs) were
      aggregated to derive overall hepatic PDFF values. Demographic, anthropometric,
      clinical, and laboratory variables were included in a multivariate analysis to
      determine predictors of hepatic steatosis grades (based on established PDFF
      cutoffs). Hepatic steatosis grades derived from single vs aggregated ROIs were
      compared. RESULTS: Hepatic steatosis was observed in 25% of patients (19% grade
      1; 3% grade 2; 3% grade 3). Controlling for all other variables, the odds of
      hepatic steatosis increased by 7%-9% (P <.001) for each whole point increase in
      body mass index (BMI), whereas elevated serum bilirubin was associated with lower
      odds of hepatic steatosis (P = .002). Race, diabetes mellitus, dyslipidemia, and
      metabolic syndrome were not independently predictive of hepatic steatosis when
      controlling for other variables (eg, BMI). Employing single ROIs (rather than
      three aggregated ROIs) resulted in incorrect steatosis grading in up to 8.0% of
      patients. CONCLUSION: Many adult patients undergoing liver MRI at a tertiary care
      center have hepatic steatosis, with larger BMIs as the only independent predictor
      of higher grades. This information can be used by clinicians at such centers to
      make evidence-based decisions about when to test for hepatic steatosis in their
      patients.

PMID- 29199058
TI  - One-Year Follow-up Study Detects Myocardial Changes with Cardiovascular Magnetic
      Resonance Tagging in Active Rheumatoid Arthritis.
AB  - RATIONALE AND OBJECTIVES: To evaluate the effects of 1 year of medical treatment
      on myocardial function in active rheumatoid arthritis (RA). MATERIALS AND
      METHODS: Thirty-nine female patients with RA without any known cardiovascular
      disease underwent a cardiovascular magnetic resonance (CMR) examination before
      and after 1 year of antirheumatic treatment. The population comprised untreated
      active early RA (ERA) and chronic RA patients, who were grouped accordingly. The
      CMR protocol included volumetric determinations, late gadolinium enhancement
      imaging, myocardial tagging, and native T1 mapping. DAS28-CRP disease activity
      scores were calculated before and after the treatment. RESULTS: Results are
      reported as median (quartile 1-quartile 3). Time to peak diastolic filling rate
      improved in ERA (495 [443-561] ms vs 441 [340-518] ms, P = .018). Peak diastolic
      mean mid short-axis circumferential strain rate of all six segments was improved
      (82 [74-91] %/s vs 91 [77-100] %/s, P = .05), particularly in the anterior
      segment (82 [63-98] %/s vs 86 [77-109] %/s, P = .013). DAS28-CRP decreased in ERA
      (3.8 [3.2-4.1] vs 1.6 [1.4-2.2], P < .001). In chronic RA, no statistically
      significant improvement was detected. CONCLUSIONS: Early treatment of active RA
      is important, as myocardial function detected with CMR tagging improved in ERA in
      parallel with decreasing inflammatory activity.

PMID- 29199059
TI  - Preventing Overdiagnosis of Acetabular Labral "Tears" in 40-Plus-year-old
      Patients: Shouldn't these be called Labral "Fissures" Instead?
AB  - Acetabular labral tears represent a common finding on magnetic resonance imaging
      of the hip. Labral tears can arise from a multitude of underlying pathological
      processes or they may be an asymptomatic incidental finding. The prevalence of
      labral tears and their lack of specificity make this an area vulnerable to
      potential overdiagnosis. The overdiagnosis of labral tears leads to overtreatment
      by exposing patients to unnecessary surgeries as well as complications ranging
      from unsatisfying outcomes to deep venous thrombosis. This risk is compounded by
      the tabloid popularization of labral surgeries by celebrities such as Lady Gaga,
      which could potentiate patient perception of a two-tiered level of health care.
      Following a similar situation with spine nomenclature, one solution to this issue
      is to reclassify "labral tears" as "labral fissures" in some or all cases to
      mitigate the acute traumatic connotation of the term "tear."

PMID- 29199060
TI  - Total Joint Arthroplasty in Patients With Parkinson's Disease: Survivorship,
      Outcomes, and Reasons for Failure.
AB  - BACKGROUND: Gait instability and muscle rigidity are known characteristics of
      Parkinson's disease (PD), putting PD patients at risk for complications following
      total joint arthroplasty (TJA). The outcomes of Parkinson's patients undergoing
      TJA are largely unknown. This study evaluated the outcomes of TJA in this
      population. METHODS: A single institution retrospective cohort of 123 TJAs (52
      hips, 71 knees) from 2000 to 2016 was reviewed. An electronic chart query was
      performed using International Classification of Diseases, Ninth revision codes to
      identify this population. A manual chart review was performed to confirm the
      diagnosis of PD, survivorship, and reason for failure. A control cohort was
      matched 2:1 based on age, body mass index, joint, and comorbidities. Outcomes
      were assessed using revision for any reason as the primary endpoint. Functional
      outcomes were assessed using Short-Form 12 scores. RESULTS: At an average follow
      up of 5.3 years, 23.6% of patients required revision surgery. The most common
      reasons for revision for total knee arthroplasty (TKA) were periprosthetic
      infection and for total hip arthroplasty (THA) were periprosthetic fracture and
      dislocation. Overall survivorship of TJA at years 2, 5, and 10 respectively were
      94.9%, 87.9%, and 72.3%. The survivorship of TKA was 95.2%, 89.8%, and 66.2%. THA
      implant survivorship was 94.3%, 85.3%, and 78.7%. Functional score improvement
      was less in PD cohort than the control. CONCLUSION: Patients with PD are at
      increased risk for complications, particularly periprosthetic infection following
      TKA and periprosthetic fracture and dislocation following THA. Despite this
      increased risk of complications, patients with PD can demonstrate improved
      functional outcomes but not as high as patients without PD. Patients with PD
      should be counseled appropriately prior to undergoing TJA.

PMID- 29199061
TI  - Should Medicare Remove Total Knee Arthroplasty From Its Inpatient Only List? A
      Total Knee Arthroplasty Is Not a Partial Knee Arthroplasty.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services have solicited
      comments to consider removing total knee arthroplasty (TKA) from the Inpatient
      Only list, as it has done for unicompartmental knee arthroplasty (UKA). The
      purpose of this study is to determine whether Medicare-aged patients undergoing
      TKA had comparable outcomes to those undergoing UKA. METHODS: We queried the
      American College of Surgeons-National Surgical Quality Improvement Program
      database for all patients aged 65 years or older who underwent elective TKA or
      UKA from 2014 and 2015. Demographic variables, comorbidities, length of stay
      (LOS), 30-day complication, and readmission rates were compared between UKA and
      TKA patients. A multivariate regression analysis was then performed to identify
      independent risk factors for complications and hospital LOS greater than 1 day.
      RESULTS: Of the 50,487 patients in the study, there were 49,136 (97%) TKA
      patients and 1351 UKA patients (3%). Medicare-aged TKA patients had a longer mean
      LOS (2.97 vs 1.57 days, P < .001), had a higher complication rate (9% vs 3%, P <
      .001), and were more likely to be discharged to a rehabilitation facility (31% vs
      9%, P < .001) than Medicare-aged UKA patients. When controlling for other
      variables, TKA patients were more likely to experience a complication (odds
      ratio, 2.562; P < .001) and require LOS >1 day (odds ratio, 14.679; P < .001)
      than UKA patients. CONCLUSION: TKA procedure in the Medicare population is an
      independent risk factor for increased complications and LOS compared to UKA.
      Policymakers should use caution extrapolating UKA data to TKA patients and
      recognize the inherent disparities between the 2 procedures.

PMID- 29199062
TI  - Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery:
      Formulation development, stability issues, basic considerations and applications.
AB  - The use of nanoemulsion in augmenting dermal and transdermal effectiveness of
      drugs has now well established. The development of nanoemulsion based semisolid
      dosage forms is an active area of present research. However, thickening or liquid
      to-semisolid conversion of the nanoemulsions provides opportunities to the
      formulation scientist to explore novel means of solving instability issues during
      transformation. Extending knowledge about the explicit role of nature/magnitude
      of zeta potential, types of emulsifiers and selection of appropriate semisolid
      bases could place these versatile carriers from laboratory to industrial scale.
      This article reviews the progressive advancement in the delivery of medicament
      via nanoemulsion with special reference to the dermal and transdermal
      administration. It is attempted to explore the most suitable semi solid dosage
      form for the particular type of nanoemulsion (o/w, w/o and others) and effect of
      particle size and zeta potential on the delivery of drugs through dermal or
      transdermal route. Finally, this review also highlights the basic principles and
      fundamental considerations of nanoemulsion manufacture, application of
      nanoemulsion based semisolid dosage forms in the dermal/transdermal
      administration and basic considerations during the nanoemulsion absorption into
      and through skin.

PMID- 29199063
TI  - Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain
      targeting studies.
AB  - The treatment of neurodegenerative and psychiatric disorders remains a challenge
      in medical research. Several strategies have been developed over the years,
      either to overcome the blood-brain barrier or to achieve a safer or faster brain
      delivery, one of them being intranasal (IN) administration. The possibility of
      direct nose-to-brain transport offers enhanced targeting and reduced systemic
      side effects. Nevertheless, labile, low soluble, low permeant and/or less potent
      drugs might need a formulation other than the common solutions or suspensions.
      For that, the formulation of nanosystems is considered to be a promising
      approach, since it can protect drugs from chemical and/or metabolic degradation,
      enhance their solubility, or offer transport through biological membranes.
      However, the understanding of the factors promoting efficient brain targeting
      when using nanosystems through the nasal route is currently patchy and
      incomplete. The main purpose of the present review was to evaluate the
      association between brain delivery efficacy (in terms of brain targeting, brain
      bioavailability and time to reach the brain) and nanosystem type. For that, we
      performed a systematic bibliographic search and analysis. Furthermore, study
      designs, nanosystem properties, and reporting quality were also analyzed and
      discussed. It was found a high heterogeneity in how pre-clinical brain targeting
      studies have been conducted, analyzed and reported in scientific literature,
      which surely originates a significant degree of bias and data dispersion. This
      review attempts to provide some systematization recommendations, which may be
      useful for researchers entering the field, and assist in increasing the
      uniformity of future reports. The analysis of literature data confirmed that
      there is evidence of the advantage of the IN route (when compared to the
      intravenous route) and in using carrier nanosystems (when compared to IN
      solutions) for brain delivery of a large set of drugs. Among the most represented
      nanosystem classes, microemulsions had some of the lowest pharmacokinetic ratios
      values, while polymeric micelles had some of the best. Nevertheless, brain
      targeting efficacy comparisons between nanosystem groups had little statistical
      significance, and the superiority of the polymeric micelles group disappeared
      when nanosystems were compared to the respective IN drug solutions. In fact, some
      drugs reached the brain so efficiently, even as drug solutions, that further
      benefit from formulating them into nanosystems became less evident.

PMID- 29199064
TI  - Subchronic bisphenol S exposure affects liver function in mice involving
      oxidative damage.
AB  - Bisphenol S (BPS) has been widely used in the manufacturing industry as a
      substitute for bisphenol A (BPA). Emerging evidences, mostly from in vitro
      studies, suggest that BPS may exert a variety of toxicological effects and have
      the potential to induce oxidative stress. Nevertheless, few data are available
      for the in vivo effects of BPS on liver, an important target of drug toxicity.
      For the first time, our study systematically investigated the effects of BPS at a
      wide range of doses on liver function in mice upon oral administration. We found
      that treatment with 5000 MUg/kg BPS for 8 weeks resulted in liver injury with
      increased plasma levels of alanine aminotransferase, aspartate aminotransferase
      and total bilirubin, as well as defects in hepatic morphology. Moreover, such
      exposure to BPS induced oxidative stress in the liver of mice by decreasing
      activities of antioxidant enzymes, and increasing lipid peroxidation level and
      expression of two biomarker genes, HO-1 and GADD45B. No significant changes were
      observed for treatment with lower doses (5-500 MUg/kg) or shorter duration (4
      weeks). In conclusion, subchronic BPS exposure could affect liver function in
      mice by inducing oxidative damage, indicating that BPS may be not an absolutely
      safe alternative to BPA.

PMID- 29199065
TI  - Safety evaluation of DAS-44406-6 soybeans in Wistar rats.
AB  - A 90-day in-country feeding trial in Wistar rats was conducted at Tianjin
      Laboratory in China to assess toxicity of diets containing DAS-44406-6 soybean
      meal. There were no treatment-related changes observed when compared with the non
      GM isoline control groups but histopathologically, 2 of 10 high-dose females were
      reported to show kidney lesions. However, these findings contrasted with the
      absence of any treatment-related kidney lesions in 3 separate 90-day toxicity
      studies previously conducted in Sprague Dawley rats. Strain difference is not
      expected in the kidney response, and based on the low incidence and contrary
      evidence from previous studies, it is likely that these lesions were of
      spontaneous origin, or artefactual. To determine that the lesions observed were
      not treatment-related in Wistar rats, a specific follow-up confirmatory study was
      conducted under Good Laboratory Practices (GLP) in the Wistar strain of rats
      following an identical study design to the Tianjin study. To increase the power
      of detecting effects, twice the number of animals per group (20/sex/group) were
      used, and no treatment-related kidney histopathological changes were observed.
      Based on these results and entire weight of evidence evaluation, it is concluded
      that the histopathological changes previously noted in the 2 female Wistar rats
      of Tianjin study were not treatment-related and that DAS-44406-6 soybeans are as
      safe as conventional non-GM soybeans.

PMID- 29199066
TI  - Abuse liability assessment for biologic drugs - All molecules are not created
      equal.
AB  - The development of novel drug candidates involves the thorough evaluation of
      potential efficacy and safety. To facilitate the safety assessment in light of
      global increases in prescription drug misuse/abuse, health authorities have
      developed guidance documents which provide a framework for evaluating the abuse
      liability of candidate therapeutics. The guidances do not distinguish between
      small molecules and biologics/biotherapeutics; however, there are key differences
      between these classes of therapeutics which are important drivers of concern for
      abuse. An analysis of these properties, including ability to distribute to the
      central nervous system, pharmacokinetic properties (e.g., half-life and
      metabolism), potential for off-target binding, and the physiochemical
      characteristics of biologic drug products suggests that the potential for abuse
      of a biologic is limited. Many marketed antibodies and recombinant proteins have
      been associated with adverse effects such as headache and dizziness. However,
      biologics have not historically engendered the rapid-onset psychoactive effects
      typically present for drugs of abuse, thus further underscoring their low risk
      for abuse potential. The factors to be taken into consideration before conducting
      nonclinical abuse liability studies with biologics are described herein;
      importantly, the aggregate assessment of these factors leads to the conclusion
      that abuse liability studies are unlikely to be necessary for this class of
      therapeutics.

PMID- 29199067
TI  - Pressure-induced microstructural changes in porcine tricuspid valve leaflets.
AB  - : Quantifying mechanically-induced changes in the tricuspid valve extracellular
      matrix (ECM) structural components, e.g. collagen fiber spread and distribution,
      is important as it determines the overall macro-scale tissue responses and
      subsequently its function/malfunction in physiological/pathophysiological states.
      For example, functional tricuspid regurgitation, a common tricuspid valve
      disorder, could be caused by elevated right ventricular pressure due to pulmonary
      hypertension. In such patients, the geometry and the normal function of valve
      leaflets alter due to chronic pressure overload, which could cause remodeling
      responses in the ECM and change its structural components. To understand such a
      relation, we developed an experimental setup and measured alteration of leaflet
      microstructure in response to pressure increase in porcine tricuspid valves using
      the small angle light scattering technique. The anisotropy index, a measure of
      the fiber spread and distribution, was obtained and averaged for each region of
      the anterior, posterior, and septal leaflet using four averaging methods. The
      average anisotropy indices (mean +/- standard error) in the belly region of the
      anterior, posterior, and septal leaflets of non-pressurized valves were found to
      be 12 +/- 2%, 21 +/- 3% and 12 +/- 1%, respectively. For the pressurized valve,
      the average values of the anisotropy index in the belly region of the anterior,
      posterior, and septal leaflets were 56 +/- 5%, 39 +/- 7% and 32 +/- 5%,
      respectively. Overall, the average anisotropy index was found to be higher for
      all leaflets in the pressurized valves as compared to the non-pressurized valves,
      indicating that the ECM fibers became more aligned in response to an increased
      ventricular pressure. STATEMENT OF SIGNIFICANCE: Mechanics plays a critical role
      in development, regeneration, and remodeling of tissues. In the current study, we
      have conducted experiments to examine how increasing the ventricular pressure
      leads to realignment of protein fibers comprising the extracellular matrix (ECM)
      of the tricuspid valve leaflets. Like many other tissues, in cardiac valves, cell
      matrix interactions and gene expressions are heavily influenced by changes in the
      mechanical microenvironment at the ECM/cellular level. We believe that our study
      will help us better understand how abnormal increases in the right ventricular
      pressure (due to pulmonary hypertension) could change the structural architecture
      of tricuspid valve leaflets and subsequently the mechanical microenvironment at
      the ECM/cellular level.

PMID- 29199068
TI  - Same Same But Different: Processing Words in the Aging Brain.
AB  - Reading is not only one of the most appreciated leisure activities of the elderly
      but it clearly helps older people to maintain functional independence, which has
      a significant impact on life quality. Yet, very little is known about how aging
      affects the neural circuits of the processes that underlie skilled reading.
      Therefore, the aim of the present study was to systematically investigate the
      neural correlates of sublexical, orthographic, phonological and lexico-semantic
      processing in the aging brain. Using functional magnetic resonance imaging, we
      recorded brain activity of younger (N = 20; 22-35 years) and older (N = 38; 65-76
      years) adults during letter identification, lexical decision, phonological
      decision and semantic categorization. Older and younger adults recruited an
      identical set of reading-related brain regions suggesting that the general
      architecture of the reading network is preserved across the lifespan. However, we
      also observed age-related differences in brain activity in the subcomponents of
      the reading network. Age-related differences were most prominent during
      phonological and orthographic processing possibly due to a failure of older
      adults to inhibit non-optimal reading strategies. Neural effects of aging were
      also observed outside reading-related circuits, especially in frontal midline
      regions. These regions might be involved because of their important role in
      memory, attention and executive control functions and their potential role in
      resting-state networks.

PMID- 29199069
TI  - VGLUT1 Binding to Endophilin or Intersectin1 and Dynamin Phosphorylation in a
      Diurnal Context.
AB  - Glutamate is concentrated into synaptic vesicles (SV) by the vesicular glutamate
      transporters (VGLUT) 1 and 2. VGLUTs also harbor a Na+/Pi-transport activity when
      residing at the plasma membrane. Here we aimed to identify whether the diurnal
      switches of VGLUT1 parallels interactions with or modification of endocytic
      proteins. VGLUT1 and dynamin bind to SH3 domains of either endophilin (Enph) or
      intersectin 1 (ITSN1) harboring one or five SH3 domains A-E, respectively. We
      followed diurnal variations by pull down experiments using SH3 fusion protein and
      brains from mice entrained in a strict 24-h light-dark cycle (12-h light
      Zeitgeber (ZT) 0, 6; 12-h dark ZT 12 and 18). In pull downs with EnphSH3
      interaction with VGLUT1 is high during the resting light and reduced during the
      active dark period while dynamin binding does not vary. This diurnal light/dark
      pattern depends on a functional period 2 gene and changes when animals are kept
      in complete darkness. Pull downs using ITSN1SH3 A reveal diurnally varying
      binding of VGLUT1 with slightly reduced VGLUT1/dynamin ratios at the beginning of
      the light (ZT 0) or the dark (ZT 12) period. Phosphorylation increases binding of
      VGLUT1 but not of dynamin to EnphSH3. In contrast binding of dynamin to ITSN1SH3
      A decreases under phosphorylating conditions with no changes in VGLUT1 binding.
      Phosphorylation of dynamin at Ser 774 is high at ZT 6 and ZT 18 when more VGLUT1
      is at the plasma membrane but low at ZT 0 and ZT 12 the diurnal peaks of VGLUT1
      endocytosis. In conclusion the diurnally varying endocytosis of VGLUT1 involves
      differential interactions with the SH3 domains of Enph and ITSN1 and correlates
      with the de-phosphorylation of dynamin1.

PMID- 29199070
TI  - Anaesthetic efficacy of 4% articaine compared with 2% mepivacaine: a randomized,
      double-blind, crossover clinical trial.
AB  - The aim of this study was to evaluate the clinical efficacy of 4% articaine (Ar4)
      compared to 2% mepivacaine (Me2), both in combination with 1:100,000 epinephrine,
      in a unique soft tissue model. This was a randomized, double-blind, crossover
      clinical trial. The anaesthetic was applied to the lower lip using a computerized
      local delivery system. The following were evaluated: blood flow, thermal
      sensation, pressure and proprioception, extent of anaesthesia, gradual
      elimination, and the final duration of the effect of the anaesthesia. Seventy-two
      volunteers completed all parts of the study. Significant differences, which
      indicated better effectiveness of Me2 compared to Ar4, were observed in the
      following tests: reduction in blood flow (larger in the Me2 group); anaesthetized
      area at 30min (larger in the Me2 group); pressure tests; temperature tests after
      20min; fine and discriminatory proprioception tests after 20min. The volunteers'
      perception of anaesthesia at 30, 40, 50, and 60min was superior for Me2 at all
      recorded time points. The duration of anaesthesia was also superior for Me2. The
      overall performance of Me2 was superior to Ar4, implying that Me2 provides a more
      effective anaesthesia in terms of depth, extent, and duration.

PMID- 29199071
TI  - In reference to "Central nervous system anomalies in craniofacial microsomia: a
      systematic review".

PMID- 29199072
TI  - Maternal Brain TNF-alpha Programs Innate Fear in the Offspring.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine that not only coordinates
      local and systemic immune responses [1, 2] but also regulates neuronal functions.
      Most prominently, glia-derived TNF-alpha has been shown to regulate homeostatic
      synaptic scaling [3-6], but TNF-alpha-null mice exhibited no apparent cognitive
      or emotional abnormalities. Instead, we found a TNF-alpha-dependent
      intergenerational effect, as mothers with a deficit in TNF-alpha programmed their
      offspring to exhibit low innate fear. Cross-fostering and conditional knockout
      experiments indicated that a TNF-alpha deficit in the maternal brain, rather than
      in the hematopoietic system, and during gestation was responsible for the low
      fear offspring phenotype. The level of innate fear governs the balance between
      exploration/foraging and avoidance of predators and is thus fundamentally
      important in adaptation, fitness, and survival [7]. Because maternal exercise and
      activity are known to reduce both brain TNF-alpha [8] and offspring innate fear
      [9], whereas maternal stress has been reported to increase brain TNF-alpha [10]
      and offspring fear and anxiety [11, 12], maternal brain TNF-alpha may report
      environmental conditions to promote offspring behavioral adaptation to their
      anticipated postnatal environment.

PMID- 29199074
TI  - The Plastid Genome in Cladophorales Green Algae Is Encoded by Hairpin
      Chromosomes.
AB  - Virtually all plastid (chloroplast) genomes are circular double-stranded DNA
      molecules, typically between 100 and 200 kb in size and encoding circa 80-250
      genes. Exceptions to this universal plastid genome architecture are very few and
      include the dinoflagellates, where genes are located on DNA minicircles. Here we
      report on the highly deviant chloroplast genome of Cladophorales green algae,
      which is entirely fragmented into hairpin chromosomes. Short- and long-read high
      throughput sequencing of DNA and RNA demonstrated that the chloroplast genes of
      Boodlea composita are encoded on 1- to 7-kb DNA contigs with an exceptionally
      high GC content, each containing a long inverted repeat with one or two protein
      coding genes and conserved non-coding regions putatively involved in replication
      and/or expression. We propose that these contigs correspond to linear single
      stranded DNA molecules that fold onto themselves to form hairpin chromosomes. The
      Boodlea chloroplast genes are highly divergent from their corresponding
      orthologs, and display an alternative genetic code. The origin of this highly
      deviant chloroplast genome most likely occurred before the emergence of the
      Cladophorales, and coincided with an elevated transfer of chloroplast genes to
      the nucleus. A chloroplast genome that is composed only of linear DNA molecules
      is unprecedented among eukaryotes, and highlights unexpected variation in plastid
      genome architecture.

PMID- 29199073
TI  - Theta Oscillations in the Human Medial Temporal Lobe during Real-World Ambulatory
      Movement.
AB  - The theta rhythm-a slow (6-12 Hz) oscillatory component of the local field
      potential-plays a critical role in spatial navigation and memory by coordinating
      the activity of neuronal ensembles within the medial temporal lobe (MTL).
      Although theta has been extensively studied in freely moving rodents, its
      presence in humans has been elusive and primarily investigated in stationary
      subjects. Here we used a unique clinical opportunity to examine theta within the
      human MTL during untethered, real-world ambulatory movement. We recorded
      intracranial electroencephalographic activity from participants chronically
      implanted with the wireless NeuroPace responsive neurostimulator (RNS) and
      tracked their motion with sub-millimeter precision. Our data revealed that
      movement-related theta oscillations indeed exist in humans, such that theta power
      is significantly higher during movement than immobility. Unlike in rodents,
      however, theta occurs in short bouts, with average durations of ~400 ms, which
      are more prevalent during fast versus slow movements. In a rare opportunity to
      study a congenitally blind participant, we found that both the prevalence and
      duration of theta bouts were increased relative to the sighted participants.
      These results provide critical support for conserved neurobiological
      characteristics of theta oscillations during ambulatory spatial navigation, while
      highlighting some fundamental differences across species in these oscillations
      between humans and rodents.

PMID- 29199075
TI  - Nigrotectal Stimulation Stops Interval Timing in Mice.
AB  - Considerable evidence implicates the basal ganglia in interval timing, yet the
      underlying mechanisms remain poorly understood. Using a novel behavioral task, we
      demonstrate that head-fixed mice can be trained to show the key features of
      timing behavior within a few sessions. Single-trial analysis of licking behavior
      reveals stepping dynamics with variable onset times, which is responsible for the
      canonical Gaussian distribution of timing behavior. Moreover, the duration of
      licking bouts decreased as mice became sated, showing a strong motivational
      modulation of licking bout initiation and termination. Using optogenetics, we
      examined the role of the basal ganglia output in interval timing. We stimulated a
      pathway important for licking behavior, the GABAergic output projections from the
      substantia nigra pars reticulata to the deep layers of the superior colliculus.
      We found that stimulation of this pathway not only cancelled licking but also
      delayed the initiation of anticipatory licking for the next interval in a
      frequency-dependent manner. By combining quantitative behavioral analysis with
      optogenetics in the head-fixed setup, we established a new approach for studying
      the neural basis of interval timing.

PMID- 29199076
TI  - Tension-Dependent Stretching Activates ZO-1 to Control the Junctional
      Localization of Its Interactors.
AB  - Tensile forces regulate epithelial homeostasis, but the molecular mechanisms
      behind this regulation are poorly understood. Using structured illumination
      microscopy and proximity ligation assays, we show that the tight junction protein
      ZO-1 exists in stretched and folded conformations within epithelial cells,
      depending on actomyosin-generated force. We also show that ZO-1 and ZO-2 regulate
      the localization of the transcription factor DbpA and the tight junction membrane
      protein occludin in a manner that depends on the organization of the actin
      cytoskeleton, myosin-II activity, and substrate stiffness, resulting in
      modulation of gene expression, cell proliferation, barrier function, and cyst
      morphogenesis. Pull-down experiments show that interactions between N-terminal
      (ZPSG) and C-terminal domains of ZO-1 prevent binding of DbpA to the ZPSG,
      suggesting that force-dependent intra-molecular interactions regulate ZPSG
      binding to ligands within cells. In vivo and in vitro experiments also suggest
      that ZO-1 heterodimerization with ZO-2 promotes the stretched conformation and
      ZPSG interaction with ligands. Magnetic tweezers single-molecule experiments
      suggest that pN-scale tensions (~2-4 pN) are sufficient to maintain the stretched
      conformation of ZO-1, while keeping its structured domains intact, and that 5-20
      pN force is required to disrupt the interaction between the extreme C-terminal
      and the ZPSG domains of ZO-1. We propose that tensile forces regulate epithelial
      homeostasis by activating ZO proteins through stretching, to control the
      junctional recruitment and downstream signaling of their interactors.

PMID- 29199077
TI  - Evolution and Genetics of Precocious Burrowing Behavior in Peromyscus Mice.
AB  - A central challenge in biology is to understand how innate behaviors evolve
      between closely related species. One way to elucidate how differences arise is to
      compare the development of behavior in species with distinct adult traits [1].
      Here, we report that Peromyscus polionotus is strikingly precocious with regard
      to burrowing behavior, but not other behaviors, compared to its sister species P.
      maniculatus. In P. polionotus, burrows were excavated as early as 17 days of age,
      whereas P. maniculatus did not build burrows until 10 days later. Moreover, the
      well-known differences in burrow architecture between adults of these species-P.
      polionotus adults excavate long burrows with an escape tunnel, whereas P.
      maniculatus dig short, single-tunnel burrows [2-4]-were intact in juvenile
      burrowers. To test whether this juvenile behavior is influenced by early-life
      environment, we reciprocally cross-fostered pups of both species. Fostering did
      not alter the characteristic burrowing behavior of either species, suggesting
      that these differences are genetic. In backcross hybrids, we show that precocious
      burrowing and adult tunnel length are genetically correlated and that a P.
      polionotus allele linked to tunnel length variation in adults is also associated
      with precocious onset of burrowing in juveniles, suggesting that the same genetic
      region-either a single gene with pleiotropic effects or linked genes-influences
      distinct aspects of the same behavior at these two life stages. These results
      raise the possibility that genetic variants affect behavioral drive (i.e.,
      motivation) to burrow and thereby affect both the developmental timing and adult
      expression of burrowing behavior.

PMID- 29199078
TI  - Ocean-wide Drivers of Migration Strategies and Their Influence on Population
      Breeding Performance in a Declining Seabird.
AB  - Which factors shape animals' migration movements across large geographical
      scales, how different migratory strategies emerge between populations, and how
      these may affect population dynamics are central questions in the field of animal
      migration [1] that only large-scale studies of migration patterns across a
      species' range can answer [2]. To address these questions, we track the migration
      of 270 Atlantic puffins Fratercula arctica, a red-listed, declining seabird,
      across their entire breeding range. We investigate the role of demographic,
      geographical, and environmental variables in driving spatial and behavioral
      differences on an ocean-basin scale by measuring puffins' among-colony
      differences in migratory routes and day-to-day behavior (estimated with
      individual daily activity budgets and energy expenditure). We show that
      competition and local winter resource availability are important drivers of
      migratory movements, with birds from larger colonies or with poorer local winter
      conditions migrating further and visiting less-productive waters; this in turn
      led to differences in flight activity and energy expenditure. Other behavioral
      differences emerge with latitude, with foraging effort and energy expenditure
      increasing when birds winter further north in colder waters. Importantly, these
      ocean-wide migration patterns can ultimately be linked with breeding performance:
      colony productivity is negatively associated with wintering latitude, population
      size, and migration distance, which demonstrates the cost of competition and
      migration on future breeding and the link between non-breeding and breeding
      periods. Our results help us to understand the drivers of animal migration and
      have important implications for population dynamics and the conservation of
      migratory species.

PMID- 29199079
TI  - Nociceptive Cortical Activity Is Dissociated from Nociceptive Behavior in Newborn
      Human Infants under Stress.
AB  - Newborn infants display strong nociceptive behavior in response to tissue
      damaging stimuli, and this is accompanied by nociceptive activity generated in
      subcortical and cortical areas of the brain [1, 2]. In the absence of verbal
      report, these nociceptive responses are used as measures of pain sensation in
      newborn humans, as they are in animals [3, 4]. However, many infants are raised
      in a physiologically stressful environment, and little is known about the effect
      of background levels of stress upon their pain responses. In adults, acute
      physiological stress causes hyperalgesia [5-7], and increased background stress
      increases pain [8-10], but these data cannot necessarily be extrapolated to
      infants. Here we have simultaneously measured nociceptive behavior, brain
      activity, and levels of physiological stress in a sample of 56 newborn human
      infants aged 36-42 weeks. Salivary cortisol (hypothalamic pituitary axis), heart
      rate variability (sympathetic adrenal medullary system), EEG event-related
      potentials (nociceptive cortical activity), and facial expression (behavior) were
      acquired in individual infants following a clinically required heel lance. We
      show that infants with higher levels of stress exhibit larger amplitude cortical
      nociceptive responses, but this is not reflected in their behavior. Furthermore,
      while nociceptive behavior and cortical activity are normally correlated, this
      relationship is disrupted in infants with high levels of physiological stress.
      Brain activity evoked by noxious stimulation is therefore enhanced by stress, but
      this cannot be deduced from observation of pain behavior. This may be important
      in the prevention of adverse effects of early repetitive pain on brain
      development.

PMID- 29199080
TI  - Improved Modeling of Compositional Heterogeneity Supports Sponges as Sister to
      All Other Animals.
AB  - The relationships at the root of the animal tree have proven difficult to
      resolve, with the current debate focusing on whether sponges (phylum Porifera) or
      comb jellies (phylum Ctenophora) are the sister group of all other animals [1-5].
      The choice of evolutionary models seems to be at the core of the problem because
      Porifera tends to emerge as the sister group of all other animals ("Porifera
      sister") when site-specific amino acid differences are modeled (e.g., [6, 7]),
      whereas Ctenophora emerges as the sister group of all other animals ("Ctenophora
      sister") when they are ignored (e.g., [8-11]). We show that two key phylogenomic
      datasets that previously supported Ctenophora-sister [10, 12] display strong
      heterogeneity in amino acid composition across sites and taxa and that no
      routinely used evolutionary model can adequately describe both forms of
      heterogeneity. We show that data-recoding methods [13-15] reduce compositional
      heterogeneity in these datasets and that models accommodating site-specific amino
      acid preferences can better describe the recoded datasets. Increased model
      adequacy is associated with significant topological changes in support of
      Porifera-sister. Because adequate modeling of the evolutionary process that
      generated the data is fundamental to recovering an accurate phylogeny [16-20],
      our results strongly support sponges as the sister group of all other animals and
      provide further evidence that Ctenophora-sister represents a tree reconstruction
      artifact. VIDEO ABSTRACT.

PMID- 29199081
TI  - Robotic finger perturbation training improves finger postural steadiness and hand
      dexterity.
AB  - The purpose of the study was to understand the effect of robotic finger
      perturbation training on steadiness in finger posture and hand dexterity in
      healthy young adults. A mobile robotic finger training system was designed to
      have the functions of high-speed mechanical response, two degrees of freedom, and
      adjustable loading amplitude and direction. Healthy young adults were assigned to
      one of the three groups: random perturbation training (RPT), constant force
      training (CFT), and control. Subjects in RPT and CFT performed steady posture
      training with their index finger using the robot in different modes: random force
      in RPT and constant force in CFT. After the 2-week intervention period,
      fluctuations of the index finger posture decreased only in RPT during steady
      position-matching tasks with an inertial load. Purdue pegboard test score
      improved also in RPT only. The relative change in finger postural fluctuations
      was negatively correlated with the relative change in the number of completed
      pegs in the pegboard test in RPT. The results indicate that finger posture
      training with random mechanical perturbations of varying amplitudes and
      directions of force is effective in improving finger postural steadiness and hand
      dexterity in healthy young adults.

PMID- 29199082
TI  - DACT2 Epigenetic Stimulator Exerts Dual Efficacy for Colorectal Cancer Prevention
      and Treatment.
AB  - DACT2, a tumor suppressor gene in various tumors, is frequently down-regulated
      via hypermethylation. We found DACT2 gene expressions were dramatically silenced
      (P = 0.002, n = 8) in our clinical colorectal cancer (CRC) tissues, and TCGA data
      revealed DACT2 hypermethylation correlated to CRC poor prognosis (P = 0.0129, HR
      = 0.2153, n = 248). Thus, by screening twelve nutritional compounds, we aimed to
      find out an effective DACT2 epigenetic stimulator to determine whether DACT2
      epigenetic restoration could reverse CRC tumorigenesis. We found that kaempferol
      significantly increased DACT2 expressions up to 3.47-fold in three CRC cells
      (HCT116, HT29, and YB5). Furthermore, kaempferol remarkably decreased DACT2
      methylation (range: 19.58%-67.00%, P < 0.01), while increased unmethylated DACT2
      by 13.72-fold (P < 0.01) via directly binding to DNA methyltransferases DNMT1. By
      epigenetic reactivating DACT2 transcription, kaempferol notably inhibited nuclear
      beta-catenin expression to inactivate Wnt/beta-catenin pathway, which
      consequently restricted CRC cells proliferation and migration. Moreover, in
      AOM/DSS-induced CRC tumorigenesis, kaempferol-demethylated DACT2 effectively
      decreased tumor load (range: 50.00%-73.52%, P < 0.05). By determining the
      chemopreventive and chemotherapeutic efficacy of a novel DACT2 demethylating
      stimulator, we demonstrated that DACT2 epigenetic restoration could successfully
      slow down and reverse CRC tumorigenesis.

PMID- 29199083
TI  - Factors Correlating With Microsurgical Performance: A Clinical and Experimental
      Study.
AB  - BACKGROUND: Microsurgery is one the most complex surgical skills to master. The
      factors correlating with microsurgical performance, however, are poorly
      understood. Understanding these factors will aid in the training and assessment
      of microsurgeons. METHODS: A total of 29 microsurgery fellows enrolled in a
      dedicated 1-year microsurgery fellowship were included in the study. For the
      clinical evaluations, microsurgical anastomosis performance was evaluated during
      multiple procedures in the operating room at the start, midpoint, and end of the
      fellowship by all departmental faculty using a validated microsurgical assessment
      tool. For the laboratory evaluations, blinded video recordings of each fellow
      performing an arterial femoral anastomosis in a live rat model at the start and
      end of the fellowship were evaluated using 3 validated microsurgical global
      ratings scale tools. Correlations between performance and the factors assessed by
      the tools were evaluated. RESULTS: In the clinical study there were a total of
      474 anastomosis evaluations; clinical performance correlated best with speed,
      instrument handling, and motion. In the laboratory study 58 evaluations were
      conducted, and performance tracked most closely with instrument handling, flow of
      operation, and operative steps, as well as correlating significantly inversely
      with time taken. The most common errors committed were unequal stitch bites,
      wrong grasp/damage tissue, and loose knot. CONCLUSIONS: Speed, both subjective
      and objective, instrument handling, operative flow, and motion, were relevant to
      performance of a microsurgical anastomosis. A prospective trial is now necessary
      to determine whether these factors should be considered in definitions of
      competency in microsurgery training pathways.

PMID- 29199084
TI  - Ethnicity influences cardiovascular outcomes and complications in patients with
      type 2 diabetes.
AB  - AIM: To determine whether cardiovascular outcomes in type 2 diabetes (T2D) differ
      according to ethnicity, and whether ethnicity influences the effect of gender on
      these outcomes in Caucasians, East-Southeast-Asians, Middle-Easterners, South
      Asians and Pacific-Islanders. METHODS: We compared demographics, HbA1c, lipid
      profile, renal function markers, and prevalence of macrovascular and
      microvascular complications between ethnic groups. Cross-sectional data was
      prospectively collected from 204 consecutive patients at Westmead Hospital's T2D
      clinic from April-October 2015. Univariate analysis was performed using chi
      squared test for categorical data, and Mann-Whitney-U or Kruskal-Wallis test for
      continuous data. RESULTS: Compared to Caucasians, South-Asians were diagnosed
      younger, were currently younger, had lower body-mass-index (BMI) and better renal
      function but higher rates of non-ST-elevation myocardial infarction (STEMI, 21.7%
      versus 3.5%, p<0.05). East-Southeast-Asians had lower BMI but more nephropathy
      than Caucasians (59% versus 39%, p<0.05). East-Southeast-Asian males had fewer
      CVD than Caucasians, but this protection was absent in East-Southeast-Asian
      females. Middle-Easterners had more non-STEMI than Caucasians (5.3% vs 3.5%,
      p<0.05). Middle-Eastern females were not at lower CVD risk than males. Caucasians
      had most PVD (20% versus 6%, p<0.05). CONCLUSIONS: Ethnicity influences rates of
      diabetes-related complications. Female CVD protection is altered in some groups.
      Ethnicity should be considered in assessing CVD and complications risk.

PMID- 29199085
TI  - Diagnostic Performance of Mammographic Texture Analysis in the Differential
      Diagnosis of Benign and Malignant Breast Tumors.
AB  - BACKGROUND: The purpose of this study was to investigate the diagnostic
      performance of mammographic texture analysis in the differential diagnosis of
      benign and malignant breast tumors. PATIENTS AND METHODS: Digital mammography
      images were obtained from the Picture Archiving and Communication System at our
      institute. Texture features of mammographic images were calculated. Mann-Whitney
      U test was used to identify differences between the benign and malignant group.
      The receiver operating characteristic (ROC) curve analysis was used to assess the
      diagnostic performance of texture features. RESULTS: Significant differences of
      texture features of histogram, gray-level co-occurrence matrix (GLCM) and run
      length matrix (RLM) were found between the benign and malignant breast group (P <
      .05). The area under the ROC (AUROC) of histogram, GLCM, and RLM were 0.800,
      0.787, and 0.761, with no differences between them (P > .05). The AUROCs of
      imaging-based diagnosis, texture analysis, and imaging-based diagnosis combined
      with texture analysis were 0.873, 0.863, and 0.961, respectively. When imaging
      based diagnosis was combined with texture analysis, the AUROC was higher than
      that of imaging-based diagnosis or texture analysis (P < .05). CONCLUSION:
      Mammographic texture analysis is a reliable technique for differential diagnosis
      of benign and malignant breast tumors. Furthermore, the combination of imaging
      based diagnosis and texture analysis can significantly improve diagnostic
      performance.

PMID- 29199086
TI  - Treatment Patterns and Outcomes of Patients With Metastatic ER+/HER-2- Breast
      Cancer: A Multicountry Retrospective Medical Record Review.
AB  - PURPOSE: To describe treatment patterns and clinical outcomes among
      postmenopausal women with metastatic ER+/HER-2- breast cancer treated with >= 2
      lines of endocrine therapy or chemotherapy in the metastatic setting. PATIENTS
      AND METHODS: Retrospective medical record review was conducted in Canada, the
      United Kingdom, Belgium, the Netherlands, Germany, Spain, and France. Baseline
      characteristics were assessed at the date of metastatic diagnosis. Time to
      progression (TTP) and overall survival (OS) were estimated by Kaplan-Meier
      analyses. Multivariable models were used to evaluate factors associated with
      disease progression. RESULTS: Among 901 patients, the mean (standard deviation)
      age at metastatic diagnosis was 62.7 (9.7) years; 67.26% were initially diagnosed
      with metastatic disease, 66.37% had visceral disease, and 25.86% had bone
      metastasis only. Two-thirds of patients received endocrine therapy for first-line
      treatment. Fifty-nine percent received endocrine therapy, and 37.18% received
      chemotherapy for second-line treatment. The most common reason for stopping
      treatment was disease progression. Median (95% confidence interval [CI]) TTP on
      first-line endocrine treatment was 11.3 (10.7-12.2) months and 7.0 (6.3-7.9)
      months on chemotherapy. Median (95% CI) TTP on second-line endocrine therapy was
      8.1 (7.5-9.1) months and 6.1 (5.4-6.8) months on chemotherapy. Median (95% CI) OS
      was 68.6 (52.2-83.7) months after first-line endocrine therapy and 39.7 (34.5
      48.7) months after chemotherapy. CONCLUSION: Patients prescribed endocrine
      therapy had longer TTP and OS than patients prescribed chemotherapy in the first-
      and second-line settings. Disease progression was less than a year regardless of
      treatment type and line of therapy, indicating a need for treatments that delay
      progression without affecting quality of life among these patients.

PMID- 29199087
TI  - Primary total knee arthroplasty for acute fracture around the knee.
AB  - Relatively poor results have been reported with open reduction and internal
      fixation of complex fractures around the knee in elderly osteoporotic patients,
      and primary total knee arthroplasty (TKA) has been proposed as an alternative
      solution. While limiting the number of procedures, it meets two prerequisites:
      (1) to save the patient's life, thanks to early weight-bearing, to limit
      decubitus complications; and (2) to save knee function and patient autonomy,
      thanks to early knee mobilization. There are 3 main indications: complex
      articular fractures in elderly patients with symptomatic osteoarthritis prior to
      fracture; complex articular fractures of the tibial plateau in elderly patients
      whose bone quality makes internal fixation hazardous; and major destruction of
      the distal femur in younger patients. Although admitted in emergency, these
      patients require adequate preoperative management, including a multidisciplinary
      approach to manage comorbidities, control of anemia and pain, and assessment and
      management of vascular and cutaneous conditions. Preoperative planning is
      crucial, to order appropriate implants and materials that may be needed
      intraoperatively. Surgical technique is based on the basic principles of revision
      surgery as regards choice of implant, steps of reconstruction, bone defect
      management and implant fixation. For complex fractures of the distal femur,
      primary temporary reduction is a useful "trick", to determine the level of the
      joint line and femoral rotation. Complementary internal fixation may be required
      in case of diaphyseal extension of the fracture and to prevent inter-prosthetic
      fractures. In the literature, the results of primary TKA for fracture are
      encouraging and better than for secondary TKA after failure of non-operative
      treatment or internal fixation, with lower rates of revision and complications,
      earlier full weight-bearing and better functional results. Loss of autonomy is,
      however, frequent, and 1-year mortality is high, especially following complex
      femoral fractures in the elderly.

PMID- 29199088
TI  - A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph
      Nodes.
AB  - Most T1 colorectal cancers treated by radical surgery can now be cured by
      endoscopic submucosal dissection. Although 70%-80% of T1 colorectal cancers are
      classified as high risk, <16% of these patients actually have lymph node
      metastases. Biomarkers are needed to identify patients with T1 cancers with the
      highest risk of metastasis, to prevent unnecessary radical surgery. We collected
      data from The Cancer Genome Atlas and identified 5 microRNAs (MIR32, MIR181B,
      MIR193B, MIR195, and MIR411) with significant changes in expression in T1 and T2
      colorectal cancers with vs without lymph node metastases. Levels of the 5
      microRNAs identified patients with lymph node invasion by T1 or T2 cancers with
      an area under the receiver operating characteristic curve (AUROC) value of 0.84.
      We validated these findings in 2 cohorts of patients with T1 cancers, using
      findings from histology as the reference. The 5-microRNA signature identified T1
      cancers with lymph node invasion in cohort 1 with an AUROC value of 0.83, and in
      cohort 2 with an AUROC value of 0.74. When we analyzed biopsy samples from
      untreated patients, the 5-microRNA signature identified cancers with lymph node
      metastases with an AUROC value of 0.77. The 5-microRNA therefore identifies high
      risk T1 colorectal cancers with a greater degree of accuracy than currently used
      pathologic features.

PMID- 29199089
TI  - Applying asymptotic methods to synthetic biology: Modelling the reaction kinetics
      of the mevalonate pathway.
AB  - The mevalonate pathway is normally found in eukaryotes, and allows for the
      production of isoprenoids, a useful class of organic compounds. This pathway has
      been successfully introduced to Escherichia coli, enabling a biosynthetic
      production route for many isoprenoids. In this paper, we develop and solve a
      mathematical model for the concentration of metabolites in the mevalonate pathway
      over time, accounting for the loss of acetyl-CoA to other metabolic pathways.
      Additionally, we successfully test our theoretical predictions experimentally by
      introducing part of the pathway into Cupriavidus necator. In our model, we
      exploit the natural separation of time scales as well as of metabolite
      concentrations to make significant asymptotic progress in understanding the
      system. We confirm that our asymptotic results agree well with numerical
      simulations, the former enabling us to predict the most important reactions to
      increase isopentenyl diphosphate production whilst minimizing the levels of HMG
      CoA, which inhibits cell growth. Thus, our mathematical model allows us to
      recommend the upregulation of certain combinations of enzymes to improve
      production through the mevalonate pathway.

PMID- 29199090
TI  - Voluntary vaccination dilemma with evolving psychological perceptions.
AB  - Voluntary vaccination is a universal control protocol for infectious diseases.
      Yet there exists a social dilemma between individual benefits and public health:
      non-vaccinators free ride via the herd immunity from adequate vaccinators who
      bear vaccination cost. This is due to the interplay between disease prevalence
      and individual vaccinating behavior. To complicate matters further, individual
      vaccinating behavior depends on the perceived vaccination cost rather than the
      actual one. The perception of vaccination cost is an individual trait, which
      varies from person to person, and evolves in response to the disease prevalence
      and vaccination coverage. To explore how evolving perception shapes individual
      vaccinating behavior and thus the vaccination dynamics, we provide a model
      combining epidemic dynamics with evolutionary game theory which captures the
      voluntary vaccination dilemma. In particular, individuals adjust their perception
      based on the inertia effect in psychology and then update their vaccinating
      behavior through imitating the behavior of a more successful peer. We find that
      i) vaccination is acceptable when the expected vaccination cost considering
      perception and actual vaccination cost is less than the maximum of the expected
      non-vaccination cost; ii) the evolution of perception is a "double-edged sword"
      for vaccination dynamics: it can improve vaccination coverage when most
      individuals perceive exaggerated vaccination cost, and it inhibits vaccination
      coverage in the other cases.

PMID- 29199091
TI  - Nonpalpable testes: Ultrasound and contralateral testicular hypertrophy predict
      the surgical access, avoiding unnecessary laparoscopy.
AB  - INTRODUCTION: In up to 20% of patients presenting with undescended testes, one or
      both are non-palpable. Whereas the most reliable means to exclude an abdominal
      testis is laparoscopy, there has been a lot of debate about the role of inguinal
      ultrasound (US) in detecting non-palpable inguinal testis. While we do not aim to
      add another paper claiming the benefits of US, we wanted to determine the excess
      capability of US to determine the correct surgical approach - inguinal or
      laparoscopy. In the light of avoiding unnecessary diagnostic laparoscopies, even
      the cost-effectiveness raised in many current papers might be called into
      question. PATIENTS AND METHODS: Of a total of 684 boys who underwent surgery for
      undescended testes at our department between 2011 and 2014, in 58 (8.5%), one or
      both testes were neither palpable preoperatively nor under general anesthesia.
      These boys were examined by two experienced pediatric urologists clinically as
      well as by US. Besides the size of the contralateral testis, the presence of a
      testis in the inguinal channel was investigated. The additional impact of US over
      clinical exam and consideration of the size of the contralateral testis was
      assessed by means of intra-individual comparisons using Cochran-Q as well as
      McNemar tests. RESULTS: Clinical exam without considering the size of the
      contralateral testis had a sensitivity of 9% (95% CI 2-24%) and a specificity of
      100% (95% CI 86-100%) to accurately predict the surgical approach deemed
      appropriate postoperatively. The consideration of the size of the contralateral
      testis - taken as an isolated factor - accurately predicted the surgical approach
      with a sensitivity of 21% (95% CI 9-38%) and a specificity of 88% (95% CI 68
      97%). Ultrasound accounted for a sensitivity of 53% (95% CI 35-70%) and a
      specificity of 100% (95% CI 86-100%). The addition of US increased the
      sensitivity to correctly predict an inguinal incision from 29% to 71% and
      specificity slightly increased from 88% to 92%. This difference is significant (p
      = 0.008) in the bilateral McNemar test (Figure). CONCLUSION: Inguinal US of non
      palpable testes and measurement of the contralateral testis are synergistic in
      predicting the surgical approach. The addition of ultrasound to a clinical exam,
      performed also under general anesthesia and by an experienced pediatric urologist
      significantly increases the prediction of the correct surgical approach. Our
      results translate into five boys needing an US of the NPT to prevent one
      laparoscopy. Whereas cost-effectiveness of US might be debatable in regard to
      different healthcare systems, it is proven to be an effective, non-harmful tool
      to avoid unnecessary diagnostic laparoscopies.

PMID- 29199092
TI  - Occupational noise exposure and hypertension: the Dongfeng-Tongji Cohort Study.
AB  - The association between occupational noise exposure and hypertension is unclear.
      We aimed to explore the association in a Chinese population and to summarize our
      findings with previous published articles. The cross-sectional study included
      22,450 participants from Dongfeng-Tongji Cohort Study. In a subsample of 10,636
      subjects, we assessed the association between hearing loss and hypertension. For
      the meta-analysis, we searched PubMed and EMBASE until April 2017, and the pooled
      odds ratio (OR) was combined using a random effect model. Compared with
      participants without occupational noise exposure, the risk of hypertension was
      significantly higher for noise exposure duration >=20 (OR = 1.09, 95% confidence
      interval [CI] = 1.00-1.18). In the sex-specific analysis, the association was
      only significantly pronounced in males (OR = 1.16, 95% CI = 1.03-1.31), but not
      in females (OR = 1.01, 95% CI = 0.88-1.14). In the subsample analyses, hearing
      loss, which was an indicator for exposure to loud noise, was associated with a
      higher risk of hypertension, especially for participants who were bilateral
      hearing loss (OR = 1.39, 95% CI = 1.24-1.54). In the meta-analysis, the pooled OR
      for the association between occupational noise exposure and hypertension was 1.25
      (95% CI = 1.10-1.42). On the basis of an indicator for exposure to occupational
      noise, the cross-sectional study and meta-analysis identified occupational noise
      exposure as a potential risk factor for increased hypertension risk.

PMID- 29199093
TI  - Evolutionary epistemology: Reviewing and reviving with new data the research
      programme for distributed biological intelligence.
AB  - Numerous studies in microbiology, eukaryotic cell biology, plant biology,
      biomimetics, synthetic biology, and philosophy of science appear to support the
      principles of the epistemological theory inspired by evolution, also known as
      "Evolutionary Epistemology", or EE. However, that none of the studies
      acknowledged EE suggests that its principles have not been formulated with
      sufficient clarity and depth to resonate with the interests of the empirical
      research community. In this paper I review evidence in favor of EE, and also
      reformulate EE principles to better inform future research. The revamped
      programme may be tentatively called Research Programme for Distributed Biological
      Intelligence. Intelligence I define as the capacity of organisms to gain
      information about their environment, process that information internally, and
      translate it into phenotypic forms. This multistage progression may be expressed
      through the acronym IGPT (information-gain-process-translate). The key principles
      of the programme may be summarized as follows. (i) Intelligence, a universal
      biological phenomenon promoting individual fitness, is required for effective
      organism-environment interactions. Given that animals represent less than 0.01%
      of the planetary biomass, neural intelligence is not the evolutionary norm. (ii)
      The basic unit of intelligence is a single cell prokaryote. All other forms of
      intelligence are derived. (iii) Intelligence is hierarchical. It ranges from
      bacteria to the biosphere or Gaia. (iv) The concept of "information" acquires a
      new meaning because information processing is at the heart of biological
      intelligence. All biological systems, from bacteria to Gaia, are intelligent,
      open thermodynamic systems that exchange information, matter and energy with the
      environment. (v) The organism-environment interaction is cybernetic. As much as
      the organism changes due to the influence of the environment, the organism's
      responses to induced changes affect the environment and subsequent organism
      environment interactions. Based on the above principles a new research agenda can
      be formulated to explore different forms of biological intelligence.

PMID- 29199094
TI  - alpha-Conotoxins to explore the molecular, physiological and pathophysiological
      functions of neuronal nicotinic acetylcholine receptors.
AB  - The vast diversity of neuronal nicotinic acetylcholine subunits expressed in the
      central and peripheral nervous systems, as well as in non-neuronal tissues,
      constitutes a formidable challenge for researchers and clinicians to decipher the
      role of particular subtypes, including complex subunit associations, in
      physiological and pathophysiological functions. Many natural products target the
      nAChRs, but there is no richer source of nicotinic ligands than the venom of
      predatory gastropods known as cone snails. Indeed, every single species of cone
      snail was shown to produce at least one type of such alpha-conotoxins. These tiny
      peptides (10-25 amino acids), constrained by disulfide bridges, proved to be
      unvaluable tools to investigate the structure and function of nAChRs, some of
      them having also therapeutic potential. In this review, we provide a recent
      update on the pharmacology and subtype specificity of several major alpha
      conotoxins.

PMID- 29199095
TI  - Analysis of white matter characteristics with tract-based spatial statistics
      according to diffusion tensor imaging in early Parkinson's disease.
AB  - OBJECTIVE: To analyze the microstructure of brain white matter according to
      diffusion tensor imaging (DTI) based on tract-based spatial statistics (TBSS) in
      early Parkinson's disease (PD). MATERIALS AND METHODS: A total of 31 age- and sex
      matched early PD patients and 22 healthy volunteers were recruited in the present
      study. DTI was performed, and the data analyzed with fsl4.0 software. The
      fractional anisotropy (FA) was compared between both groups with an independent t
      test, and the differential area was analyzed. White matter fiber tracts with
      significant difference in FA between the two groups were selected, and their FAs
      were measured. Pearson's correlation analysis was employed to analyze the unified
      Parkinson's disease rating scale (UPDRS) score and its association with FA of
      different tracts. RESULTS: When compared with healthy volunteers, early PD
      patients had reduced FA in the following areas: bilateral anterior corona
      radiate, upper corona radiate, fasciculus arcuatus, crus anterius capsulae
      internae, crus posterius capsulae internae, capsula externa, posterior thalamic
      radiation, optic radiation, sagittal layer (including fasciculus arcuatus and
      inferior fronto-occipital fasciculus), crura fornicis, stria terminalis, fornix,
      genu, body and pad of corpus callosum, left unciform fasciculus, right cingulate
      bundle, right medipeduncle, and arcuate fibers in the bilateral frontal,
      temporal, and occipital lobes (P < 0.05). When compared with healthy volunteers,
      early PD patients showed abnormal FA of fasciculus in the white matter mainly in
      following areas: bilateral crus anterius capsulae internae, bilateral capsula
      externa, right anterior corona radiate, body and pad of bilateral corpus
      callosum, and left sagittal layer (including fasciculi longitudinalis inferior
      and fasciculus occipitofrontalis inferior) (P < 0.05). In addition, in early PD
      patients, the UPDRS score and movement score had no relationship with the FA of
      different fasciculi in the white matter (P > 0.05). CONCLUSION: There is wide
      alteration of white matter microstructure in early PD patients, which is
      characterized by disruption of projection fibers in the descending pathway,
      limbic system-related fasciculi, corpus callosum, thalamus after radiation,
      posterior thalamic radiation, Gratiolet's bundle and other fasciculi in the white
      matter.

PMID- 29199096
TI  - Sexual Recovery Following Prostate Cancer: Recommendations From 2 Established
      Canadian Sexual Rehabilitation Clinics.
AB  - INTRODUCTION: Supportive sexual health care is much-needed adjuvant care to
      oncologic management for men with prostate cancer (PCa). AIM: To inspire the
      initiation of biopsychosocial sexual health programming where it does not exist
      and to inform program enhancement in existing sexual rehabilitation clinics
      (SRCs). METHODS: This article reviews the combined 30-year experience of 2 well
      established Canadian SRCs for men and their partners after PCa treatments,
      interwoven with empirical evidence. MAIN OUTCOME MEASURE: To comprehensively
      review the biopsychosocial approach to sexual health assessment of men with PCa
      and their partners to direct the practicalities of running a successful and
      sustainable SRC. RESULTS: A full description of the biomedical and psychosocial
      approaches, inclusive of comprehensive sexual function, the penile rehabilitation
      controversy, and other medical and relationship issues affecting sexual
      adjustment, is provided to highlight the relevance of proper assessment and
      follow-through for sexual adaptation and adjustment. 10 recommendations for a
      successful SRC are discussed, including the principles behind developing a
      sustainable business plan, staff acquisition and training, budget, integration of
      treatment and research priorities, respectful and multidisciplinary approaches to
      care, and suggestions of visit formats, protocols, and questionnaires. We
      recommend a phased approach of an SRC into usual care with the option to provide
      accessible and equitable care to patients not within proximal access of treating
      institutions. CONCLUSION: Sexual rehabilitation after treatment for PCa requires
      a complex treatment process. Providing sustainable sexual rehabilitation
      programming under the financially strained environment of the Canadian medical
      system is a challenge; therefore, to provide Canadian patients and their partners
      with comprehensive cancer care, they deserve a biopsychosocial approach combined
      with a creative and systematic implementation strategy. Elliott S, Matthew A.
      Sexual Recovery Following Prostate Cancer: Recommendations From 2 Established
      Canadian Sexual Rehabilitation Clinics. Sex Med Rev 2018;6:279-294.

PMID- 29199097
TI  - Coagulase-Negative Staphylococcal Strain Prevents Staphylococcus aureus
      Colonization and Skin Infection by Blocking Quorum Sensing.
AB  - Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus are part of the
      natural flora of humans and other mammals. We found that spent media from the
      CoNS species Staphylococcus caprae can inhibit agr-mediated quorum sensing by all
      classes of S. aureus. A biochemical assessment of the inhibitory activity
      suggested that the S. caprae autoinducing peptide (AIP) was responsible, and mass
      spectrometric analysis identified the S. caprae AIP as an eight-residue peptide
      (YSTCSYYF). Using a murine model of intradermal MRSA infection, the therapeutic
      efficacy of synthetic S. caprae AIP was evident by a dramatic reduction in both
      dermonecrotic injury and cutaneous bacterial burden relative to controls.
      Competition experiments between S. caprae and MRSA demonstrated a significant
      reduction in MRSA burden using murine models of both skin colonization and
      intradermal infection. Our findings indicate that important interactions occur
      between commensals that can impact disease outcomes and potentially shape the
      composition of the natural flora.

PMID- 29199099
TI  - Prevention of HIV transmission by antiretroviral therapy.

PMID- 29199098
TI  - Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug
      Efficacy and Alter Immune Function.
AB  - Bactericidal antibiotics alter microbial metabolism as part of their lethality
      and can damage mitochondria in mammalian cells. In addition, antibiotic
      susceptibility is sensitive to extracellular metabolites, but it remains unknown
      whether metabolites present at an infection site can affect either treatment
      efficacy or immune function. Here, we quantify local metabolic changes in the
      host microenvironment following antibiotic treatment for a peritoneal Escherichia
      coli infection. Antibiotic treatment elicits microbiome-independent changes in
      local metabolites, but not those distal to the infection site, by acting directly
      on host cells. The metabolites induced during treatment, such as AMP, reduce
      antibiotic efficacy and enhance phagocytic killing. Moreover, antibiotic
      treatment impairs immune function by inhibiting respiratory activity in immune
      cells. Collectively, these results highlight the immunomodulatory potential of
      antibiotics and reveal the local metabolic microenvironment to be an important
      determinant of infection resolution.

PMID- 29199101
TI  - Versatility of putative aromatic aminotransferases from Candida albicans.
AB  - Amino acids constitute the key sources of nitrogen for growth of Candida
      albicans. In order to survive inside the host in different and rapidly changing
      environments, this fungus must be able to adapt via its expression of genes for
      amino acid metabolism. We analysed the ARO8, ARO9, YER152C, and BNA3 genes with
      regards to their role in the nutritional flexibility of C. albicans. CaAro8p is
      undoubtedly the most versatile enzyme among the aminotransferases investigated.
      It is involved in the catabolism of histidine, lysine, and aromatic amino acids
      as well as in l-Lys, Phe and Tyr biosynthesis. CaAro9p participates in the
      catabolism of aromatic amino acids and lysine at high concentrations of these
      compounds, with no biosynthetic role. Conversely, the CaYer152Cp catalytic
      potential for aromatic amino acid catabolism observed in vitro appears to be of
      little importance in vivo. Neither biosynthetic nor catabolic roles of CaBan3p
      were observed for any proteinogenic amino acid. Finally, none of the analysed
      aminotransferases was solely responsible for the catabolism of a single
      particular amino acid or its biosynthesis.

PMID- 29199100
TI  - Universal test and treat and the HIV epidemic in rural South Africa: a phase 4,
      open-label, community cluster randomised trial.
AB  - BACKGROUND: Universal antiretroviral therapy (ART), as per the 2015 WHO
      recommendations, might reduce population HIV incidence. We investigated the
      effect of universal test and treat on HIV acquisition at population level in a
      high prevalence rural region of South Africa. METHODS: We did a phase 4, open
      label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South
      Africa. We included individuals residing in the communities who were aged 16
      years or older. The clusters were composed of aggregated local areas
      (neighbourhoods) that had been identified in a previous study in the Hlabisa
      subdistrict. The study statisticians randomly assigned clusters (1:1) with
      MapInfo Pro (version 11.0) to either the control or intervention communities,
      stratified on the basis of antenatal HIV prevalence. We offered residents
      repeated rapid HIV testing during home-based visits every 6 months for about 4
      years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58
      cluster-years) and referred HIV-positive participants to trial clinics for ART
      (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of
      CD4 cell count (intervention) or according to national guidelines (initially
      <=350 cells per MUL and <500 cells per MUL from January, 2015; control).
      Participants and investigators were not masked to treatment allocation. We used
      dried blood spots once every 6 months provided by participants who were HIV
      negative at baseline to estimate the primary outcome of HIV incidence with
      cluster-adjusted Poisson generalised estimated equations in the intention-to
      treat population after 58 cluster-years of follow-up. This study is registered
      with ClinicalTrials.gov, number NCT01509508, and the South African National
      Clinical Trials Register, number DOH-27-0512-3974. FINDINGS: Between March 9,
      2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible
      individuals. Of 17 808 (67%) individuals with a first negative dried blood spot
      test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503
      seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was
      2.11 per 100 person-years (95% CI 1.84-2.39) in the intervention group and 2.27
      per 100 person-years (2.00-2.54) in the control group (adjusted hazard ratio
      1.01, 95% CI 0.87-1.17; p=0.89). We documented one case of suicidal attempt in a
      woman following HIV seroconversion. 128 patients on ART had 189 life-threatening
      or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of
      1367 in the intervention group (p=0.83). INTERPRETATION: The absence of a
      lowering of HIV incidence in universal test and treat clusters most likely
      resulted from poor linkage to care. Policy change to HIV universal test and treat
      without innovation to improve health access is unlikely to reduce HIV incidence.
      FUNDING: ANRS, GiZ, and 3ie.

PMID- 29199102
TI  - Effect of repeated adrenocorticotropic hormone administration on reproductive
      function and hair cortisol concentration during the estrous cycle in goats.
AB  - Measurement of the cortisol concentration in hair has been used as an index of
      chronic stress in several species including humans, wildlife and domestic
      animals. However, how accurately the cortisol concentration in hair reflects the
      changes in circulating cortisol concentrations has not been well documented. The
      objective of the present study was to examine the effect of repeated
      adrenocorticotropic hormone (ACTH) administration on the reproductive function
      during the estrous cycle and hair cortisol concentrations in goats. In experiment
      1, goats were administered ACTH (0.625 IU/10 kg of body weight, n = 6) or saline
      (n = 6) intramuscularly once a day for 7 days on Day 11-17 of the estrous cycle
      (day 0 was the day of ovulation). In experiment 2, goats were administered ACTH
      (0.625 IU/10 kg of body weight, n = 6) or saline (n = 6) intramuscularly twice a
      day on Day 11-24 of the estrous cycle. Blood samples were collected 0, 0.5, and 6
      h after first administration to determine the circulating cortisol
      concentrations. Hair was clipped at 0, 1, and 2 months after the start of
      administration. In both experiments, the plasma cortisol concentration increased
      at 0.5 h and returned to baseline at 6 h after ACTH administration. During the
      experiments, estrus was observed in most animals in ACTH and saline groups (6/6
      and 4/6 in experiment 1 and 5/6 and 6/6 in experiment 2, respectively) and
      ovulation was observed in all goats examined. However, the number of ovulatory
      follicles was significantly different between the ACTH and saline groups, and the
      maximal diameter of ovulatory follicles tended to be different (P = .07) between
      the ACTH and saline groups. In experiment 1, the hair cortisol concentration was
      not influenced by the ACTH administration throughout the sampling period. In
      experiment 2, the hair cortisol concentration in the ACTH group was greater at 1
      month after administration than the pre-administration value, but was not
      significantly different at 2 months. These results suggest that repeated ACTH
      administration affects the development and ovulatory process of ovarian follicles
      and analysis of the hair cortisol concentration can be used for assessing
      relatively long-term changes in cortisol concentration in the circulation.

PMID- 29199103
TI  - Diversion of the long-chain acyl-ACP pool in Synechocystis to fatty alcohols
      through CRISPRi repression of the essential phosphate acyltransferase PlsX.
AB  - Fatty alcohol production in Synechocystis sp. PCC 6803 was achieved through
      heterologous expression of the fatty acyl-CoA/ACP reductase Maqu2220 from the
      bacteria Marinobacter aquaeolei VT8 and the fatty acyl-ACP reductase DPW from the
      rice Oryza sativa. These platform strains became models for testing multiplex
      CRISPR-interference (CRISPRi) metabolic engineering strategies to both improve
      fatty alcohol production and to study membrane homeostasis. CRISPRi allowed
      partial repression of up to six genes simultaneously, each encoding enzymes of
      acyl-ACP-consuming pathways. We identified the essential phosphate
      acyltransferase enzyme PlsX (slr1510) as a key node in C18 fatty acyl-ACP
      consumption, repression of slr1510 increased octadecanol productivity threefold
      over the base strain and gave the highest specific titers reported for this host,
      10.3mgg-1 DCW. PlsX catalyzes the first committed step of phosphatidic acid
      synthesis, and has not been characterized in Synechocystis previously. We found
      that accumulation of fatty alcohols impaired growth, altered the membrane
      composition, and caused a build-up of reactive oxygen species.

PMID- 29199105
TI  - Relicts of the lost arc: High-throughput sequencing of the Eutrichomyias rowleyi
      (Aves: Passeriformes) holotype uncovers an ancient biogeographic link between the
      Philippines and Fiji.
AB  - Molecular studies have revealed a number of cases in which traditional
      assessments of evolutionary relationships have been incorrect. This has
      implications not only for systematics and taxonomy but also for our understanding
      of how diversity patterns on Earth have been formed. Here, we use high-throughput
      sequencing technology to obtain molecular data from the holotype specimen of the
      elusive Eutrichomyias rowleyi, which is endemic to the Indonesian island of
      Sangihe. We show that E. rowleyi unexpectedly is a member of the family
      Lamproliidae, which dates back some 20 Million years and only include two other
      species, Lamprolia victoriae from Fiji and Chaetorhynchus papuensis from New
      Guinea. Tectonic reconstructions suggest that the Melanesian island arc, which
      included land masses on the northern edge of the Australian plate (present day
      New Guinea) stretched as a string of islands from the Philippines (including
      proto-Sangihe) to Fiji from 25 to 20 My. Consequently, our results are indicative
      of an ancient distribution along the Melanesian island arc followed by
      relictualization, which led to members of the Lamproliidae to be distributed on
      widely separated islands across the Indo-Pacific.

PMID- 29199106
TI  - Recovering the evolutionary history of crowned pigeons (Columbidae: Goura):
      Implications for the biogeography and conservation of New Guinean lowland birds.
AB  - Assessing the relative contributions of immigration and diversification into the
      buildup of species diversity is key to understanding the role of historical
      processes in driving biogeographical and diversification patterns in species-rich
      regions. Here, we investigated how colonization, in situ speciation, and
      extinction history may have generated the present-day distribution and diversity
      of Goura crowned pigeons (Columbidae), a group of large forest-dwelling pigeons
      comprising four recognized species that are all endemic to New Guinea. We used a
      comprehensive geographical and taxonomic sampling based mostly on historical
      museum samples, and shallow shotgun sequencing, to generate complete mitogenomes,
      nuclear ribosomal clusters and independent nuclear conserved DNA elements. We
      used these datasets independently to reconstruct molecular phylogenies.
      Divergence time estimates were obtained using mitochondrial data only. All
      analyses revealed similar genetic divisions within the genus Goura and recovered
      as monophyletic groups the four species currently recognized, providing support
      for recent taxonomic changes based on differences in plumage characters. These
      four species are grouped into two pairs of strongly supported sister species,
      which were previously not recognized as close relatives: Goura sclaterii with
      Goura cristata, and Goura victoria with Goura scheepmakeri. While the
      geographical origin of the Goura lineage remains elusive, the crown age of 5.73
      Ma is consistent with present-day species diversity being the result of a recent
      diversification within New Guinea. Although the orogeny of New Guinea's central
      cordillera must have played a role in driving diversification in Goura, cross
      barrier dispersal seems more likely than vicariance to explain the speciation
      events having led to the four current species. Our results also have important
      conservation implications. Future assessments of the conservation status of Goura
      species should consider threat levels following the taxonomic revision proposed
      by del Hoyo and Collar (HBW and BirdLife International illustrated checklist of
      the birds of the world 1: non-passerines, 2014), which we show to be fully
      supported by genomic data. In particular, distinguishing G. sclaterii from G.
      scheepmakeri seems to be particularly relevant.

PMID- 29199107
TI  - Species limits in the Morelet's Alligator lizard (Anguidae: Gerrhonotinae).
AB  - The widely distributed, Central American anguid lizard Mesaspis moreletii is
      currently recognized as a polytypic species with five subspecies (M. m. fulvus,
      M. m. moreletii, M. m. rafaeli, M. m. salvadorensis, and M. m. temporalis). We
      reevaluated the species limits within Mesaspis moreletii using DNA sequences of
      one mitochondrial and three nuclear genes. The multi-locus data set included
      samples of all of the subspecies of M. moreletii, the other species of Mesaspis
      in Central America (M. cuchumatanus and M. monticola), and some populations
      assignable to M. moreletii but of uncertain subspecific identity from Honduras
      and Nicaragua. We first used a tree-based method for delimiting species based on
      mtDNA data to identify potential evolutionary independent lineages, and then
      analized the multilocus dataset with two species delimitation methods that use
      the multispecies coalescent model to evaluate different competing species
      delimitation models: the Bayes factors species delimitation method (BFD)
      implemented in *BEAST, and the Bayesian Phylogenetics and Phylogeography (BP&P)
      method. Our results suggest that M. m. moreletii, M. m. rafaeli, M. m.
      salvadorensis, and M. m. temporalis represent distinct evolutionary independent
      lineages, and that the populations of uncertain status from Honduras and
      Nicaragua may represent additional undescribed species. Our results also suggest
      that M. m. fulvus is a synonym of M. m. moreletii. The biogeography of the
      Central American lineages of Mesaspis is discussed.

PMID- 29199104
TI  - Reverse engineering the cancer metabolic network using flux analysis to
      understand drivers of human disease.
AB  - Metabolic dysfunction has reemerged as an essential hallmark of tumorigenesis,
      and metabolic phenotypes are increasingly being integrated into pre-clinical
      models of disease. The complexity of these metabolic networks requires systems
      level interrogation, and metabolic flux analysis (MFA) with stable isotope
      tracing present a suitable conceptual framework for such systems. Here we review
      efforts to elucidate mechanisms through which metabolism influences tumor growth
      and survival, with an emphasis on applications using stable isotope tracing and
      MFA. Through these approaches researchers can now quantify pathway fluxes in
      various in vitro and in vivo contexts to provide mechanistic insights at
      molecular and physiological scales respectively. Knowledge and discoveries in
      cancer models are paving the way toward applications in other biological contexts
      and disease models. In turn, MFA approaches will increasingly help to uncover new
      therapeutic opportunities that enhance human health.

PMID- 29199110
TI  - Increased latencies to respond in a judgment bias test are not associated with
      pessimistic biases in rats.
AB  - Extinction of learning is a common, yet under-reported limitation of judgment
      bias testing methods Repeated exposure to the ambiguous probe of a judgment bias
      paradigm encourages the animal to cease display of the required behaviours.
      However, there remains a need to repeatedly test animals to achieve statistical
      power. A delicate balance therefore needs to be struck between over- and under
      exposure of the animals to the test conditions. This study presents the data of
      rats, a common animal subject of judgment bias testing. Rats were exposed to the
      ambiguous probe of a common, active-choice judgment bias test for 11 consecutive
      days. There was a significant increase in the latency to respond to the ambiguous
      probe following day 8, with no significant increase experienced for either the
      positive or less-positive probes. Following day 8 there was a significant
      increase in both optimistic and pessimistic latencies in response to the
      ambiguous probe. Therefore, repeated exposure to the ambiguous probe caused an
      increased latency in response even though optimistic interpretations were
      recorded. This implies that the use of response latency alone as a measure in
      judgment bias testing can falsely identify pessimism. Researchers should modify
      experimental design to include both choice and latency measures.

PMID- 29199111
TI  - Changes in body posture alter plasma nitrite but not nitrate concentration in
      humans.
AB  - PURPOSE: This study evaluated the change (Delta) in plasma volume (PV), nitrate
      [NO3-], and nitrite [NO2-] concentration following changes in posture in the
      presence and absence of elevated plasma [NO3-] and [NO2-] METHODS: Fourteen
      healthy participants completed two trials that were preceded by either
      supplementation with NO3--rich beetroot juice (BR; total of ~31 mmol NO3-) or no
      supplementation (CON). Both trials comprised 30 min of lying supine followed by 2
      min of standing, 2 min of sitting and 5 min of sub-maximal cycling. Measurements
      of plasma [NO3-] and [NO2-] were made by gas-phase chemiluminescence and DeltaPV
      was estimated using the Dill and Costill method. RESULTS: Plasma [NO2-] decreased
      from baseline (CON: 120 +/- 49 nM, BR: 357 +/- 129 nM) after lying supine for 30
      min (CON 77 +/- 30 nM; BR 231 +/- 92 nM, both P < 0.01) before increasing during
      standing (CON 109 +/- 42 nM; BR 297 +/- 105 nM, both P < 0.01) and sitting (CON
      131 +/- 43 nM; BR 385 +/- 125 nM, both P < 0.01). Plasma [NO2-] remained elevated
      following exercise only in CON (125 +/- 61 nM P = 0.02). Plasma [NO3-] was not
      different between measurement points in either condition (P > 0.05). PV increased
      from baseline during the supine phase before decreasing upon standing, sitting,
      and exercise in both trials (all P<0.05). CONCLUSIONS: Changing body posture
      causes rapid and consistent alterations in plasma [NO2-]. Researchers should
      therefore carefully consider the effect of posture when measuring this variable.

PMID- 29199108
TI  - Cryptic diversity in Rhampholeon boulengeri (Sauria: Chamaeleonidae), a pygmy
      chameleon from the Albertine Rift biodiversity hotspot.
AB  - Several biogeographic barriers in the Central African highlands have reduced gene
      flow among populations of many terrestrial species in predictable ways. Yet, a
      comprehensive understanding of mechanisms underlying species divergence in the
      Afrotropics can be obscured by unrecognized levels of cryptic diversity,
      particularly in widespread species. We implemented a multilocus phylogeographic
      approach to examine diversity within the widely distributed Central African pygmy
      chameleon, Rhampholeon boulengeri. Gene-tree analyses coupled with a comparative
      coalescent-based species delimitation framework revealed R. boulengeri as a
      complex of at least six genetically distinct species. The spatiotemporal
      speciation patterns for these cryptic species conform to general biogeographic
      hypotheses supporting vicariance as the main factor behind patterns of divergence
      in the Albertine Rift, a biodiversity hotspot in Central Africa. However, we
      found that parapatric species and sister species inhabited adjacent habitats, but
      were found in largely non-overlapping elevational ranges in the Albertine Rift,
      suggesting that differentiation in elevation was also an important mode of
      divergence. The phylogeographic patterns recovered for the genus-level phylogeny
      provide additional evidence for speciation by isolation in forest refugia, and
      dating estimates indicated that the Miocene was a significant period for this
      diversification. Our results highlight the importance of investigating cryptic
      diversity in widespread species to improve understanding of diversification
      patterns in environmentally diverse regions such as the montane Afrotropics.

PMID- 29199109
TI  - A supramodal role of the basal ganglia in memory and motor inhibition: Meta
      analytic evidence.
AB  - The ability to stop actions and thoughts is essential for goal-directed
      behaviour. Neuroimaging research has revealed that stopping actions and thoughts
      engage similar cortical mechanisms, including the ventro- and dorso-lateral
      prefrontal cortex. However, whether and how these abilities require similar
      subcortical mechanisms remains unexplored. Specifically of interest are the basal
      ganglia, subcortical structures long-known for their motor functions, but less so
      for their role in cognition. To investigate the potential common mechanisms in
      the basal ganglia underlying action and thought stopping, we conducted meta
      analyses using fMRI data from the Go/No-Go, Stop-signal, and Think/No-Think
      tasks. All three tasks require active stopping of prepotent actions or thoughts.
      To localise basal ganglia activations, we performed high-resolution manual
      segmentations of striatal subregions. We found that all three tasks recovered
      clusters in the basal ganglia, although the specific localisation of these
      clusters differed. Although the Go/No-Go and Stop-signal tasks are often
      interchangeably used for measuring action stopping, their cluster locations in
      the basal ganglia did not significantly overlap. These different localised
      clusters suggest that the Go/No-Go and Stop-signal tasks may recruit distinct
      basal ganglia stopping processes, and therefore should not be treated
      equivalently. More importantly, the basal ganglia cluster recovered from the
      Think/No-Think task largely co-localised with that from the Stop-signal task, but
      not the Go/No-Go task, possibly indicating that the Think/No-Think and Stop
      signal tasks share a common striatal circuitry involved in the cancellation of
      unwanted thoughts and actions. The greater similarity of the Think/No-Think task
      to the Stop-Signal rather than Go/No-Go task also was echoed at the cortical
      level, which revealed highly overlapping and largely right lateralized set of
      regions including the anterior DLPFC, VLPFC, Pre-SMA and ACC. Overall, we provide
      novel evidence suggesting not only that the basal ganglia are critical for
      thought stopping, but also that they are involved in specific stopping
      subprocesses that can be engaged by tasks in different domains. These findings
      raise the possibility that the basal ganglia may be part of a supramodal network
      responsible for stopping unwanted processes more broadly.

PMID- 29199112
TI  - [Management of patients with major beta thalassemia in a paediatric department in
      the south of Tunisia: About 26 cases].
AB  - AIM: Our objectives were to assess the management of patients with major
      thalassemia and identify the various complications and monitoring means. PATIENTS
      AND METHODS: A retrospective study was conducted on 26 beta-thalassemic patients
      in the department of paediatrics, Hedi Chaker hospital, Sfax, Tunisia during a
      period of 25 years (from 1 January 1990 to 31 December 2014). RESULTS: The mean
      age of the beginning of transfusion was 11.5 months. That was with phenotyped red
      blood cells but not leukodepleted blood. Twenty-three patients received
      chelation. Before 2001, all patients received deferoxamine, poor adherence to
      this treatment was observed in 66% of cases. It was replaced by deferiprone since
      2006 and deferasirox since 2009. A combination of 2 or 3 chelators was indicated
      for four patients. A total splenectomy was performed in 10 cases patients; it was
      due to hypersplenism. The bone marrow transplant was performed for one patient at
      the age of 9 year but it was rejected. Many complications were detected:
      endocrine complications (19 cases), immune complications (9 cases), gallbladder
      stones (5 cases), cardiac complications (4 cases), osteoporosis (3 cases),
      infectious complications (3 cases) and thromboembolic complications (2 cases). We
      noted some side effects related to chelation therapy in twelve cases. Four
      patients were dead. CONCLUSION: Improving the medical care of homozygous beta
      thalassemic children requires adherence to transfusion regimen and chelation
      therapy. Bone marrow transplantation remains the only possible curative therapy,
      which must be promoted in our country.

PMID- 29199113
TI  - Genetics and biobanks converge to resolve a vexing knowledge gap in diabetes.

PMID- 29199114
TI  - Cystic-fibrosis-related diabetes: time for oral drugs?

PMID- 29199115
TI  - Frequency and phenotype of type 1 diabetes in the first six decades of life: a
      cross-sectional, genetically stratified survival analysis from UK Biobank.
AB  - BACKGROUND: Type 1 diabetes is typically considered a disease of children and
      young adults. Genetic susceptibility to young-onset type 1 diabetes is well
      defined and does not predispose to type 2 diabetes. It is not known how
      frequently genetic susceptibility to type 1 diabetes leads to a diagnosis of
      diabetes after age 30 years. We aimed to investigate the frequency and phenotype
      of type 1 diabetes resulting from high genetic susceptibility in the first six
      decades of life. METHODS: In this cross-sectional analysis, we used a type 1
      diabetes genetic risk score based on 29 common variants to identify individuals
      of white European descent in UK Biobank in the half of the population with high
      or low genetic susceptibility to type 1 diabetes. We used Kaplan-Meier analysis
      to evaluate the number of cases of diabetes in both groups in the first six
      decades of life. We genetically defined type 1 diabetes as the additional cases
      of diabetes that occurred in the high genetic susceptibility group compared with
      the low genetic susceptibility group. All remaining cases were defined as type 2
      diabetes. We assessed the clinical characteristics of the groups with genetically
      defined type 1 or type 2 diabetes. FINDINGS: 13 250 (3.5%) of 379 511 white
      European individuals in UK Biobank had developed diabetes in the first six
      decades of life. 1286 more cases of diabetes were in the half of the population
      with high genetic susceptibility to type 1 diabetes than in the half of the
      population with low genetic susceptibility. These genetically defined cases of
      type 1 diabetes were distributed across all ages of diagnosis; 537 (42%) were in
      individuals diagnosed when aged 31-60 years, representing 4% (537/12 233) of all
      diabetes cases diagnosed after age 30 years. The clinical characteristics of the
      group diagnosed with type 1 diabetes when aged 31-60 years were similar to the
      clinical characteristics of the group diagnosed with type 1 diabetes when aged 30
      years or younger. For individuals diagnosed with diabetes when aged 31-60 years,
      the clinical characteristics of type 1 diabetes differed from those of type 2
      diabetes: they had a lower BMI (27.4 kg/m2 [95% CI 26.7-28.0] vs 32.4 kg/m2 [32.2
      32.5]; p<0.0001), were more likely to use insulin in the first year after
      diagnosis (89% [476/537] vs 6% [648/11 696]; p<0.0001), and were more likely to
      have diabetic ketoacidosis (11% [61/537] vs 0.3% [30/11 696]; p<0.0001).
      INTERPRETATION: Genetic susceptibility to type 1 diabetes results in non-obesity
      related, insulin-dependent diabetes, which presents throughout the first six
      decades of life. Our results highlight the difficulty of identifying type 1
      diabetes after age 30 years because of the increasing background prevalence of
      type 2 diabetes. Failure to diagnose late-onset type 1 diabetes can have serious
      consequences because these patients rapidly develop insulin dependency. FUNDING:
      Wellcome Trust and Diabetes UK.

PMID- 29199117
TI  - Babesia bigemina: Advances in continuous in vitro culture using serum-free medium
      supplemented with insulin, transferrin, selenite, and putrescine.

PMID- 29199118
TI  - Changes in waist circumference independent of weight: Implications for population
      level monitoring of obesity.
AB  - : Population monitoring of obesity is most commonly conducted using body mass
      index (BMI). We test the hypothesis that because of increases in waist
      circumference (WC) independent of increases in weight, BMI alone detects an
      increasingly smaller proportion of the population with obesity. METHODS:
      Australian adults with measured height, weight, and WC were selected from three
      nationally representative cross-sectional surveys (1989, 1999-2000, 2011-12;
      n=8313, 5903 & 3904). Participants were defined as having obesity using
      classifications for an obese BMI (>=30kg.m-2) and substantially-increased-risk WC
      (>=88cm [women], >=102cm [men]). Age-standardised prevalence of obesity according
      to BMI and/or WC, and the proportion of these detected by BMI and by WC were
      compared across surveys. FINDINGS: Between 1989 and 2011-12, weight and WC
      increased by 5.4kg and 10.7cm (women), and by 7.0kg and 7.3cm (men). For women
      and men, 63% and 38% of increases in WC were independent of increases in weight.
      Over this period, the prevalence of obesity according to BMI and/or WC increased
      by 25.3 percentage-points for women (18.9% to 44.3%) and 21.1 percentage-points
      for men (17.1% to 38.2%). The proportion of these detected by BMI decreased for
      women by 20 percentage-points (77% to 57%) with no change for men. The proportion
      of these detected by WC increased for women and men by 10 percentage-points (87%
      to 97%) and 6 percentage-points (85% to 91%) respectively. CONCLUSION: BMI alone
      is detecting a decreasing proportion of those considered obese by BMI and/or WC.
      Renewed discussion regarding how we monitor obesity at the population level is
      required.

PMID- 29199116
TI  - Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic
      fibrosis: a multicentre, open-label, randomised trial.
AB  - BACKGROUND: As survival among patients with cystic fibrosis has improved in
      recent decades, complications have become increasingly relevant. The most
      frequent complication is cystic-fibrosis-related diabetes. The recommended
      treatment is injected insulin, but some patients are treated with oral
      antidiabetic drugs to ease the treatment burden. We assessed the efficacy and
      safety of oral antidiabetic drugs. METHODS: We did a multicentre, open-label,
      comparative, randomised trial in 49 centres in Austria, France, Germany, and
      Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had
      newly diagnosed diabetes. We used a central randomisation schedule derived from a
      Geigy random number table to assign patients 1:1 to receive insulin or
      repaglinide, stratified by sex and age (10-15 years or >15 years). The primary
      outcome was glycaemic control assessed by mean change in HbA1c concentration from
      baseline after 24 months of treatment. Differences between groups were assessed
      by linear models. The primary and safety analyses were done in the modified
      intention-to-treat population (including patients who stopped treatment early
      because of lack of efficacy). This trial is registered with ClinicalTrials.gov,
      number NCT00662714. FINDINGS: We enrolled 34 patients in the repaglinide group
      and 41 in the insulin group, of whom 30 and 37, respectively, were included in
      the analyses. At 24 months, glycaemic control was similar in the repaglinide and
      insulin groups (mean change in HbA1c concentration from baseline 0.2% [SD 0.7%],
      1.7 mmol/mol [8.1 mmol/mol] with repaglinide vs -0.2% [1.3%], -2.7 mmol/mol,
      [14.5 mmol/mol] with insulin; mean difference between groups -0.4%, (95% CI -1.1
      to 0.2 [-4.4 mmol/mol, -11.5 to 2.7], p=0.15). The most frequent adverse events
      were pulmonary events (43 [40%] of 107 in the repaglinide group and 60 [45%] of
      133 in the insulin group), and the most frequent serious adverse events were
      pulmonary events leading to hospital admission (five [50%] of ten and seven [54%]
      of 13, respectively). INTERPRETATION: Repaglinide for glycaemic control in
      patients with cystic-fibrosis-related diabetes is as efficacious and safe as
      insulin. FUNDING: Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association,
      and Novo Nordisk.

PMID- 29199119
TI  - Sitting patterns after relocation to activity-based offices: A controlled study
      of a natural intervention.
AB  - This study determined the effect of relocating workers from traditional to
      activity-based offices on objectively measured sitting patterns. Office workers
      (n=493) from five office-sites within a large Swedish government agency were
      included in a controlled study of a natural intervention (2015-2017). At four
      sites, traditional offices were replaced by activity-based offices, while workers
      at one site with no relocation acted as controls. Sitting, standing and walking
      were measured objectively for 5-8days in a sub-sample (n=110) using accelerometry
      (Actigraph). Total sitting time (% of working time) and time spent in short
      (<5min), moderate (5-30min) and prolonged (>30min) uninterrupted periods in
      sitting were determined. Intervention effects were determined at 3- and 12-month
      follow-ups using linear mixed models adjusted for baseline age, gender and office
      type, and stratified by office-site (referencing controls). The relocation to
      activity-based offices did not result in an overall effect (across sites) on
      occupational sitting time (all p>0.05), while walking time had increased
      significantly by 1.4% of the working time at 12months compared with controls.
      Heterogeneous results were found across offices after 12months on total sitting
      time compared with controls (estimated change -18.3% time-1.4% time), prolonged
      sitting (change -18.3% to -3.8%), walking (change 0.5%-3.5%) and standing (change
      -1.4%-13.9%). In conclusion, relocation to activity-based offices had a limited
      overall effect on occupational sitting patterns in the studied organization, but
      differed considerably between office sites. Site-specific determinants of sitting
      behavior in activity-based offices need be identified.

PMID- 29199120
TI  - Understanding the molecular basis of the high oxygen affinity variant human
      hemoglobin Coimbra.
AB  - Human hemoglobin (Hb) Coimbra (betaAsp99Glu) is one of the seven betaAsp99 Hb
      variants described to date. All betaAsp99 substitutions result in increased
      affinity for O2 and decreased heme-heme cooperativity and their carriers are
      clinically characterized by erythrocytocis, caused by tissue hypoxia. Since
      betaAsp99 plays an important role in the allosteric alpha1beta2 interface and the
      mutation in Hb Coimbra only represents the insertion of a CH2 group in this
      interface, the present study of Hb Coimbra is important for a better
      understanding of the global impact of small modifications in this allosteric
      interface. We carried out functional, kinetic and dynamic characterization of
      this hemoglobin, focusing on the interpretation of these results in the context
      of a growth of the position 99 side chain length in the alpha1beta2 interface.
      Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr
      effect), and the heme-heme cooperativity was analyzed by determining the Hill
      coefficient (n), in addition to the effect of the allosteric effectors inositol
      hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer
      simulations revealed a stabilization of the R state in the Coimbra variant with
      respect to the wild type, and consistently, the T-to-R quaternary transition was
      observed on the nanosecond time scale of classical molecular dynamics
      simulations.

PMID- 29199121
TI  - Interventions targeting loneliness and social isolation among the older people:
      An update systematic review.
AB  - This systematic review aims to summarize and update the current knowledge on the
      effectiveness of the existing interventions for alleviating loneliness and social
      isolation among older persons. A search of PubMed, ISI Web of science, SCOPUS,
      The Cochrane Library, and CINAHL databases was performed. The terminology
      combined all possible alternatives of the following keywords: social isolation,
      loneliness, old people, intervention and effectiveness. Eligible studies were
      published between January 2011 and February 2016 in English or Italian language
      and regarded the implementation of loneliness/social isolation interventions
      among the older generations. Outcome measures in terms of the intervention
      effects needed to be reported. In total, 15 quantitative and five qualitative
      studies were ultimately included in this review. Eighteen interventions were
      reported across the quantitative studies. Six out of 11 group interventions
      (55%), one out of four mixed interventions (25%) and all three individual
      interventions reported at least one significant finding related to loneliness or
      social isolation. Our review suggested that new technologies and community
      engaged arts might be seen as a promising tool for tackling social isolation and
      loneliness among the older individuals. Future studies need to work on
      methodological quality and take into consideration the suggestions of the present
      literature in order to provide firm evidence.

PMID- 29199122
TI  - Spectroscopic studies of the interaction between alprazolam and apo-human serum
      transferrin as a drug carrier protein.
AB  - The interaction between apo-human serum transferrin (Apo-hTf) and alprazolam was
      investigated using various spectroscopic techniques. The drug quenched the
      fluorescence intensity of Apo-hTf and the mechanism behind the quenching was
      static. The thermodynamic parameters (DeltaG, DeltaH, and DeltaS) that obtained
      from tryptophan fluorescence study revealed that the interactions between
      alprazolam and Apo-hTf were spontaneous. Collectively, hydrophobic interactions
      and hydrogen bonding most likely played major roles in Apo-hTf/alprazolam
      interactions. Also, the absorption spectra of Apo-hTf increased in the presence
      of increasing concentration of alprazolam, reflecting Apo-hTf structural
      alteration after drug's binding. The CD results demonstrated that the Apo
      hTf/alprazolam interaction does not affect the protein secondary and tertiary
      structure significantly until the molar ratios (alprazolam/Apo-hTf) of 10, but
      the conformational changes become visible at higher molar ratios. The DSC results
      suggested that alprazolam stabilized the Apo-hTf at alprazolam/Apo-hTf molar
      ratio of 20. Based on the achieved results, this potentially therapeutic agent
      can significantly bind to Apo-hTf which also further confirmed by molecular
      docking study. This study on the interaction of the drug with Apo-hTf should be
      helpful for understanding the transportation and distribution of drugs in vivo,
      as well as the action mechanism and dynamics of a drug at the molecular level.

PMID- 29199124
TI  - Recombinant rice xylanase inhibitor (RIXI) expressed in Escherichia coli and its
      inhibitory activity on family GH11endo-xylanases.
AB  - The rice xylanase inhibitor gene, rixi, was cloned from rice genome. The open
      reading frame of rixi was 915 bp and encoded 304 amino acids with the theoretical
      molecular mass of 33.9 kDa. The rixi was inserted into the new-type expression
      vector pCold TF, and was high-level expressed in Escherichia coli BL21 (DE3). SDS
      PAGE and Western blot analysis revealed that the molecular weight of the
      recombinant rice xylanase inhibitor, namely reERIXI, was approximately 89.8 kDa.
      The reERIXI exhibited significant inhibitory activities against several family
      GH11 xylanases. After interaction with reERIXI, the residual activity of reBaxA50
      and TfxA_CD214 were 59.24% and 44.41%, respectively. The optimal temperature of
      reERIXI inhibitory activity to reBaxA50 and TfxA_CD214 were 60  degrees C and 50 
      degrees C, respectively. The thermostability assay revealed that reERIXI was
      stable below 60  degrees C. reERIXI showed high inhibitory when interacting with
      reBaxA50 and TfxA_CD214 for 30-60 min. The intrinsic fluorescence spectroscopy of
      reBaxA50 and TfxA_CD214 was quenched with increasing reERIXI concentration.
      Circular dichroism measurement revealed that ratio of helix of reBaxA50 and ratio
      of beta of TfxA_CD214 significantly decreased when interacting with reERIXI. The
      total concentration of hydrolytic products from beechwood xylan decreased when
      reERIXI was added.

PMID- 29199123
TI  - Sulfated modification of the polysaccharides from blackcurrant and their
      antioxidant and alpha-amylase inhibitory activities.
AB  - Sulfated modification was conducted to modify a homogenous polysaccharide from
      blackcurrant (BCP). The sulfated polysaccharides (SBCPs) with different degree of
      substitution (DS) were synthesized using the aminosulfonic acid (ASA)/4
      dimethylaminopyridine method by varying reaction conditions such as the mass
      ratio of ASA to BCP, temperature, and time. Three sulfated derivatives were
      chosen for high-performance gel-permeation chromatography, gas chromatography,
      fourier-transform infrared (FT-IR) spectroscopy, and nuclear magnetic resonance
      (NMR), and activity studies, designated as SBCP-1, SBCP-2, and SBCP-3 with DS of
      1.28, 0.95, and 0.53, respectively. Results showed that the sulfated modification
      was successful, and SBCPs had an increase in molecular weight compared to BCP.
      Both SBCPs and BCP were composed of rhamnose, arabinose, xylose, mannose,
      galactose, and glucose, with different molar ratios. Sulfate substitution was
      further confirmed by FT-IR and 13C NMR analysis. SBCPs exhibited excellent
      antioxidant capacities (DPPH, hydroxyl, and superoxide radical scavenging,
      reducing power, and ferrous metal-chelating capacities) and alpha-amylase
      inhibitory activity in vitro, and the activities of SBCPs were significantly
      improved in positive correlation with the DS value. This study suggested that
      SBCPs could serve as potential antioxidant agents to be used as alternative
      supplements or functional foods.

PMID- 29199125
TI  - Formulation and optimization of levofloxacin loaded chitosan nanoparticle for
      ocular delivery: In-vitro characterization, ocular tolerance and antibacterial
      activity.
AB  - In this study, chitosan nanoparticles (CH-NPs) were used to encapsulate
      antibacterial agent levofloxacin for the treatment of ocular infection. The
      chitosan nanoparticles were prepared by ionic gelation method using chitosan and
      sodium tripolyphosphate. The developed formulations were evaluated for various
      physicochemical parameters and optimized formulation was converted into the sol
      gel system to enhance the corneal residence time. The developed formulations
      showed the particle size in nanometric range with high encapsulation, and
      loading. HET-CAM test and histopathology of cornea demonstrated that optimized
      formulation was found to be non-irritant and safe for topical ophthalmic use. The
      antimicrobial study revealed that the developed formulation possesses higher
      antibacterial activity against P. aeruginosa, and S. aureus. The
      pharmacoscintigraphic study result revealed the reduced corneal clearance, naso
      lachrymal drainage as well as higher retention of LFX in comparison to LFX
      solution. Our results concluded that levofloxacin loaded chitosan nanoparticles
      in situ gel system found to be an efficient carrier for ocular delivery of
      levofloxacin.

PMID- 29199126
TI  - Chitosan produced from Mucorales fungi using agroindustrial by-products and its
      efficacy to inhibit Colletotrichum species.
AB  - This study evaluated corn steep liquor (CSL) and papaya peel juice (PPJ) in
      mixture as substrates for the cultivation (96h, 28 degrees C, pH 5.6, 150rpm) of
      Mucorales fungi for chitosan production, and determined the growth-inhibitory
      effect of the fungal chitosan (FuCS) obtained under optimized conditions against
      phytopathogenic Colletotrichum species. All Mucorales fungi tested were capable
      of growing in CSL-PPJ medium, showing FuCS production in the range of 5.02
      (Fennelomyces heterothalicus SIS 28) - 15.63mg/g (Cunninghamella elegans SIS 41).
      Highest FuCS production (37.25mg/g) was achieved when C. elegans was cultivated
      in medium containing 9.43% CSL and 42.5% PPJ. FuCS obtained under these
      conditions showed a deacetylation degree of 86%, viscosity of 120cP and molecular
      weight of 4.08*104g/mol. FuCS at 5000, 7500 and 10,000ppm inhibited the growth of
      all Colletotrichum species tested. FuCS also induced alterations in the
      morphology of C. fructicola hyphae. CSL-PPJ mixtures are suitable substrates for
      the cultivation of Mucorales fungi for FuCS production. Chitosan from C. elegans
      cultivated in CSL-PPJ medium is effective in inhibiting phytopathogenic
      Colletotrichum species.

PMID- 29199127
TI  - One-pot fabrication of chitin-shellac composite microspheres for efficient enzyme
      immobilization.
AB  - In this study, all-natural composite microspheres were fabricated through adding
      shellac into chitin solution followed by self-assembly via thermally-induced
      phase separation. The pore structure of the composite microspheres was altered
      into wedge-shape from ink-bottle-shape of the chitin microspheres, whereas, the
      crystalline structure of these two kinds of microspheres remained unaltered. The
      as-fabricated chitin-shellac composite microspheres were used for enzyme
      immobilization through adsorption. And yeast alcohol dehydrogenase (YADH) was
      chosen as the model enzyme, which is a multimer consisting of 4 subunits. The
      loading capacity of the as-prepared composite microspheres was up to 79.0mg/g
      (enzyme/carrier). The immobilized enzyme exhibited a comparable catalytic
      activity compared to its free counterpart and maintained 49.3% of its initial
      activity after 54days' storage at 4 degrees C while the free enzyme lost all its
      activity.

PMID- 29199128
TI  - Complete genome sequence of Flavobacterium kingsejongi WV39, a type species of
      the genus Flavobacterium and a microbial C40 carotenoid zeaxanthin producer.
AB  - A novel species, Flavobacterium kingsejongi WV39, isolated from feces of
      Antarctic penguins and a type species of the genus Flavobacterium, is yellow
      because it synthesizes a C40 carotenoid zeaxanthin. The complete genome of F.
      kingsejongi WV39 is made up of a single circular chromosome (4,224,053bp, 39.8%
      G+C content). Annotation analysis revealed 3,955 coding sequences, 72 RNAs (18
      rRNA+54 tRNA), and five genes involved in zeaxanthin biosynthesis. The key gene
      encoding beta-carotenoid hydroxylase (CrtZ), which is the last enzyme in the
      zeaxanthin biosynthetic pathway, was cloned and subjected to complementary
      analysis in a heterologous E. coli strain. The CrtZ of F. kingsejongi WV39 showed
      a higher activity than other reported CrtZs.

PMID- 29199129
TI  - Evaluating estrogenic and anti-estrogenic effect of endocrine disrupting
      chemicals (EDCs) by zebrafish (Danio rerio) embryo-based vitellogenin 1 (vtg1)
      mRNA expression.
AB  - By measuring the vitellogenin 1 (vtg1) expression through quantitative PCR and in
      situ hybridization, we used the zebrafish embryo as an in vivo model to access
      the estrogenic or anti-estrogenic effects of several endocrine disrupting
      chemicals (EDCs), such as natural estrogen 17beta-estradiol (E2), estriol (E3),
      synthetic hormones including diethylstilbestrol (DES), 4-octyl phenol (OP),
      bisphenol A (BPA), tamoxifen (TMX) and 3-(2,3-dibromopropyl) isocyanurate (TBC).
      According to our data, the estrogenic effect of the tested chemicals was ranked
      as: DES>E2>E3>OP>BPA, which is consistent with various in vivo and in vitro
      models. Therefore, the measurement of vtg1 gene expression in zebrafish embryos
      would be a valuable method for screening EDCs including both environmental
      estrogens and anti-estrogens.

PMID- 29199131
TI  - Combined therapy involving electroacupuncture and treadmill exercise attenuates
      demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat
      model of neonatal hypoxia-ischemia.
AB  - We investigated whether electroacupuncture (EA) and treadmill (TM) exercise
      improve behaviors related to motor and memory dysfunction in a cerebral palsy
      like rat model via activation of oligodendrogenesis. A neonatal hypoxia-ischemia
      model was created using Sprague-Dawley rats (P7), and these underwent EA
      stimulation and treadmill training from 3 to 5weeks after hypoxia-ischemia
      induction. EA treatment was delivered via electrical stimulation (2Hz, 1mA) at
      two acupoints, Baihui (GV20) and Zusanli (ST36). Behavioral tests showed that EA
      alleviated motor dysfunction caused by hypoxia-ischemia on a rotarod test, and TM
      exercise alleviated motor and memory dysfunction seen on cylinder and passive
      avoidance tests. Combined therapy with EA and TM exercise showed synergistic
      effects on the cylinder, rotarod, and catwalk tests. TM exercise significantly
      restored corpus callosum thickness, and combined therapy with EA and TM restored
      myelin basic protein (MBP) levels in this region. While EA stimulation only
      increased activation of cAMP-response element binging protein (CREB) in
      oligodendrocytes of the corpus callosum, TM exercise increased newly generated
      oligodendrocyte progenitor cells or oligodendrocytes via activation of CREB.
      Synergistic effects on oligodendrogenesis were also observed by the combined
      therapy. Furthermore, the combined therapy induced mature brain-derived
      neurotrophic factor (BDNF) expression in the cerebral cortex. These results
      demonstrate that combined therapy with EA and TM exercise may restore myelin
      components following neonatal hypoxia-ischemia via upregulation of
      oligodendrogenesis involving CREB/BDNF signaling, which subsequently improves
      motor and memory function. Therefore, combined therapy with EA and TM exercise
      offers another treatment option for functional recovery from injuries caused by
      neonatal hypoxia-ischemia, such as cerebral palsy.

PMID- 29199133
TI  - Innovative strategies for intervertebral disc regenerative medicine: From cell
      therapies to multiscale delivery systems.
AB  - As our understanding of the physiopathology of intervertebral disc (IVD)
      degeneration has improved, novel therapeutic strategies have emerged, based on
      the local injection of cells, bioactive molecules, and nucleic acids. However,
      with regard to the harsh environment constituted by degenerated IVDs, protecting
      biologics from in situ degradation while allowing their long-term delivery is a
      major challenge. Yet, the design of the optimal approach for IVD regeneration is
      still under debate and only a few papers provide a critical assessment of IVD
      specific carriers for local and sustained delivery of biologics. In this review,
      we highlight the IVD-relevant polymers as well as their design as macro-, micro-,
      and nano-sized particles to promote endogenous repair. Finally, we illustrate how
      multiscale systems, combining in situ-forming hydrogels with ready-to-use
      particles, might drive IVD regenerative medicine strategies toward innovation.

PMID- 29199130
TI  - The neurological toxicity of heavy metals: A fish perspective.
AB  - The causes of neurodegenerative diseases are complex with likely contributions
      from genetic susceptibility and environmental exposures over an organism's
      lifetime. In this review, we examine the role that aquatic models, especially
      zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity
      and nervous system function over the last decade. Focus is applied to cadmium,
      lead, and mercury as significant contributors to central nervous system
      morbidity, and the application of numerous transgenic zebrafish expressing
      fluorescent reporters in specific neuronal populations or brain regions enabling
      high-resolution neurodevelopmental and neurotoxicology research.

PMID- 29199132
TI  - BrainPhys(r) increases neurofilament levels in CNS cultures, and facilitates
      investigation of axonal damage after a mechanical stretch-injury in vitro.
AB  - : Neurobasal(r)/B27 is a gold standard culture media used to study primary
      neurons in vitro. An alternative media (BrainPhys(r)/SM1) was recently developed
      which robustly enhances neuronal activity vs. Neurobasal(r) or DMEM. To the best
      of our knowledge BrainPhys(r) has not been explored in the setting of neuronal
      injury. Here we characterized the utility of BrainPhys(r) in a model of in vitro
      mechanical-stretch injury. METHODS/RESULTS: Primary rat cortical neurons were
      maintained in classic Neurobasal(r), or sequentially maintained in Neurocult(r)
      followed by BrainPhys(r) (hereafter simply referred to as "BrainPhys(r)
      maintained neurons"). The levels of axonal markers and proteins involved in
      neurotransmission were compared on day in vitro 10 (DIV10). BrainPhys(r)
      maintained neurons had higher levels of GluN2B, GluR1, Neurofilament light/heavy
      chain (NF-L & NF-H), and protein phosphatase 2 A (PP2A) vs. neurons in
      Neurobasal(r). Mechanical stretch-injury (50ms/54% biaxial stretch) to
      BrainPhys(r) maintained neurons modestly (albeit significantly) increased 24h
      lactate dehydrogenase (LDH) levels but markedly decreased axonal NF-L levels post
      injury vs. uninjured controls or neurons given a milder 38% stretch-injury.
      Furthermore, two 54% stretch-injuries (in tandem) exacerbated 24h LDH release,
      increased alpha-spectrin breakdown products (SBDPs), and decreased Tau levels.
      Also, BrainPhys(r) maintained cultures had decreased markers of cell damage 24h
      after a single 54% stretch-injury vs. neurons in Neurobasal(r). Finally, we
      tested the hypothesis that lentivirus mediated overexpression of the pro-death
      protein RBM5 exacerbates neuronal and/or axonal injury in primary CNS cultures.
      RBM5 overexpression vs. empty-vector controls increased 24h LDH release, and SBDP
      levels, after a single 54% stretch-injury but did not affect NF-L levels or Tau.
      CONCLUSION: BrainPhys(r) is a promising new reagent which facilities the
      investigation of molecular targets involved in axonal and/or neuronal injury in
      vitro.

PMID- 29199134
TI  - The importance of fungal pathogens and antifungal coatings in medical device
      infections.
AB  - In recent years, increasing evidence has been collated on the contributions of
      fungal species, particularly Candida, to medical device infections. Fungal
      species can form biofilms by themselves or by participating in polymicrobial
      biofilms with bacteria. Thus, there is a clear need for effective preventative
      measures, such as thin coatings that can be applied onto medical devices to stop
      the attachment, proliferation, and formation of device-associated biofilms.
      However, fungi being eukaryotes, the challenge is greater than for bacterial
      infections because antifungal agents are often toxic towards eukaryotic host
      cells. Whilst there is extensive literature on antibacterial coatings, a far
      lesser body of literature exists on surfaces or coatings that prevent attachment
      and biofilm formation on medical devices by fungal pathogens. Here we review
      strategies for the design and fabrication of medical devices with antifungal
      surfaces. We also survey the microbiology literature on fundamental mechanisms by
      which fungi attach and spread on natural and synthetic surfaces. Research in this
      field requires close collaboration between biomaterials scientists,
      microbiologists and clinicians; we consider progress in the molecular
      understanding of fungal recognition of, and attachment to, suitable surfaces, and
      of ensuing metabolic changes, to be essential for designing rational approaches
      towards effective antifungal coatings, rather than empirical trial of coatings.

PMID- 29199135
TI  - Deficits in synaptic function occur at medial perforant path-dentate granule cell
      synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel
      TgF344-Alzheimer's Disease Rat Model.
AB  - Alzheimer's disease (AD) pathology begins decades prior to onset of clinical
      symptoms, and the entorhinal cortex and hippocampus are among the first and most
      extensively impacted brain regions. The TgF344-AD rat model, which more fully
      recapitulates human AD pathology in an age-dependent manner, is a next generation
      preclinical rodent model for understanding pathophysiological processes
      underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic
      alterations occur in hippocampus prior to reported learning and memory deficit is
      not known. Furthermore, it is not known if specific hippocampal synapses are
      differentially affected by progressing AD pathology, or if synaptic deficits
      begin to appear at the same age in males and females in this preclinical model.
      Here, we investigated the time-course of synaptic changes in basal transmission,
      paired-pulse ratio, as an indirect measure of presynaptic release probability,
      long-term potentiation (LTP), and dendritic spine density at two hippocampal
      synapses in male and ovariectomized female TgF344-AD rats and wildtype
      littermates, prior to reported behavioral deficits. Decreased basal synaptic
      transmission begins at medial perforant path-dentate granule cell (MPP-DGC)
      synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a
      change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d
      aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1
      synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC
      synapses in TgF344-AD rats at 6months only. Sex differences were only observed at
      CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age
      in males versus females. These are the first studies to define presymptomatic
      alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The
      time course of altered synaptic transmission mimics the spread of pathology
      through hippocampus in human AD and provides support for this model as a valuable
      preclinical tool in elucidating pathological mechanisms of early synapse
      dysfunction in AD.

PMID- 29199136
TI  - Cerebral venous collaterals: A new fort for fighting ischemic stroke?
AB  - Stroke therapy has entered a new era highlighted by the use of endovascular
      therapy in addition to intravenous thrombolysis. However, the efficacy of current
      therapeutic regimens might be reduced by their associated adverse events. For
      example, over-reperfusion and futile recanalization may lead to large infarct,
      brain swelling, hemorrhagic complication and neurological deterioration. The
      traditional pathophysiological understanding on ischemic stroke can hardly
      address these occurrences. Accumulating evidence suggests that a functional
      cerebral venous drainage, the major blood reservoir and drainage system in brain,
      may be as critical as arterial infusion for stroke evolution and clinical
      sequelae. Further exploration of the multi-faceted function of cerebral venous
      system may add new implications for stroke outcome prediction and future
      therapeutic decision-making. In this review, we emphasize the anatomical and
      functional characteristics of the cerebral venous system and illustrate its
      necessity in facilitating the arterial infusion and maintaining the cerebral
      perfusion in the pathological stroke content. We then summarize the recent
      critical clinical studies that underscore the associations between cerebral
      venous collateral and outcome of ischemic stroke with advanced imaging
      techniques. A novel three-level venous system classification is proposed to
      demonstrate the distinct characteristics of venous collaterals in the setting of
      ischemic stroke. Finally, we discuss the current directions for assessment of
      cerebral venous collaterals and provide future challenges and opportunities for
      therapeutic strategies in the light of these new concepts.

PMID- 29199138
TI  - Leaf shape diversity with an emphasis on leaf contour variation, developmental
      background, and adaptation.
AB  - Leaf shape varies markedly. Here I focus on the diversity in leaf contour, which
      can be considered marginal variation in curvature if we omit detailed marginal
      structures such as serrations. This curvature can be described by a combination
      of sigmoids: a curve for the apical half and a curve for the basal half connected
      with or without an interval. Marginal curvature is determined by the position of
      the leaf meristem, the acceleration and deceleration of cell proliferation in the
      leaf meristem, and the angle of directed cell proliferation. Several key factors
      contributing to this variation have been revealed to date, but the majority of
      the underlying genetic mechanisms are unclear. Here I provide an overview of
      current knowledge and propose future directions for the field.

PMID- 29199139
TI  - When dying is not the end: Apoptotic caspases as drivers of proliferation.
AB  - Caspases are well known for their role as executioners of apoptosis. However,
      recent studies have revealed that these lethal enzymes also have important
      mitogenic functions. Caspases can promote proliferation through autonomous
      regulation of the cell cycle, as well as by induction of secreted signals, which
      have a profound impact in neighboring tissues. Here, I review the proliferative
      role of caspases during development and homeostasis, in addition to their key
      regenerative function during tissue repair upon injury. Furthermore, the emerging
      properties of apoptotic caspases as drivers of carcinogenesis are discussed, as
      well as their involvement in other diseases. Finally, I examine further effects
      of caspases regulating death and survival in a non-autonomous manner.

PMID- 29199141
TI  - Effects of Amitriptyline and Escitalopram on Sleep and Mood in Patients With
      Functional Dyspepsia.
AB  - BACKGROUND & AIMS: Tricyclic antidepressants are effective in reducing symptoms
      of functional dyspepsia (FD). We performed a post hoc analysis of data from a
      previous randomized clinical trial to determine whether the benefits of an
      antidepressant on gastrointestinal symptoms in patients with FD were mediated by
      improving sleep or reducing anxiety. We explored the relationships between
      psychological measures, quality of sleep, and relief of symptoms. METHODS: We
      analyzed data from a multicenter, double-blind trial that evaluated the efficacy
      of antidepressants on symptoms of FD, from October 2006 through October 2012.
      Patients (n = 292) were randomly assigned to groups given 50 mg amitriptyline, 10
      mg escitalopram, or placebo for 12 weeks. During the study, participants
      completed the following validated psychological questionnaires: Symptom Check
      List 90, Symptom Somatic Checklist, Hospital Anxiety Depression Scale, Profile of
      Mood States, State Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index at
      baseline and 12 weeks following treatment. RESULTS: Baseline scores for the
      psychological and sleep measures were similar among groups; after 12 weeks there
      were no significant differences in scores among groups. Baseline mean global
      Pittsburgh Sleep Quality Index scores indicated poor sleep quality in all groups
      at baseline and after 12 weeks. Overall, antidepressants affected sleep duration
      scores: patients given amitriptyline had lower (better) scores than patients
      given placebo or escitalopram (P = .019). In all groups, responders had decreased
      anxiety and improvements in some sleep components. CONCLUSIONS: In a post hoc
      analysis of data from a clinical trial that evaluated the effects of
      antidepressants in patients with FD, amitriptyline was found to reduce symptoms
      of FD, but its mechanism is unlikely to involve reductions in psychological
      distress. The drug may modestly improve sleep. Clinicaltrials.gov no:
      NCT00248651.

PMID- 29199137
TI  - Brodmann area 10: Collating, integrating and high level processing of nociception
      and pain.
AB  - Multiple frontal cortical brain regions have emerged as being important in pain
      processing, whether it be integrative, sensory, cognitive, or emotional. One such
      region, Brodmann Area 10 (BA 10), is the largest frontal brain region that has
      been shown to be involved in a wide variety of functions including risk and
      decision making, odor evaluation, reward and conflict, pain, and working memory.
      BA 10, also known as the anterior prefrontal cortex, frontopolar prefrontal
      cortex or rostral prefrontal cortex, is comprised of at least two
      cytoarchitectonic sub-regions, medial and lateral. To date, the explicit role of
      BA 10 in the processing of pain hasn't been fully elucidated. In this paper, we
      first review the anatomical pathways and functional connectivity of BA 10.
      Numerous functional imaging studies of experimental or clinical pain have also
      reported brain activations and/or deactivations in BA 10 in response to painful
      events. The evidence suggests that BA 10 may play a critical role in the
      collation, integration and high-level processing of nociception and pain, but
      also reveals possible functional distinctions between the subregions of BA 10 in
      this process.

PMID- 29199140
TI  - Physiological functions of non-apoptotic caspase activity in the nervous system.
AB  - Caspases are cysteine proteases that play important and well-defined roles in
      apoptosis and inflammation. Increasing evidence point to alternative functions of
      caspases where restricted and localized caspase activation within neurons allows
      for a variety of non-apoptotic and non-inflammatory processes required for brain
      development and function. In this review, we highlight sublethal caspase
      functions in axon and dendrite pruning, neurite outgrowth and dendrite branches
      formation, as well as in long-term depression and synaptic plasticity.
      Importantly, as non-apoptotic activity of caspases is often confined in space and
      time in neurons, we also discuss the mechanisms that restrict caspase activity in
      order to maintain the neuronal networks in a healthy and functional state.

PMID- 29199143
TI  - Digital Single-Operator Cholangioscopy for Difficult Bile Duct Stones: Out With
      the Old in With the New?

PMID- 29199144
TI  - Alcoholic Liver Disease Replaces Hepatitis C Virus Infection as the Leading
      Indication for Liver Transplantation in the United States.

PMID- 29199146
TI  - Constipation.

PMID- 29199145
TI  - Acetaminophen-induced Acute Liver Failure Is More Common and More Severe in
      Women.
AB  - BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver
      injury (ALI) and acute liver failure (ALF) in the developed world. Sex
      differences in acetaminophen-induced hepatotoxicity have not been described.
      METHODS: We collected data from the Acute Liver Failure Study Group cohort, a
      national registry of 32 academic medical centers in North America of adults with
      ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n = 250) or
      acetaminophen-induced ALF (n = 912) from January 2000 through September 2016. We
      analyzed data on patient presentation, disease course, demographics, medical and
      psychiatric history, medication use, substance use, and details of acetaminophen
      ingestion. Sex differences in continuous and categorical variables were evaluated
      by Wilcoxon rank-sum and chi2 analysis or the Fisher exact test. Our primary aim
      was to evaluate sex differences in the presentation and clinical course of
      acetaminophen-induced acute liver injury or liver failure, and our secondary goal
      was to compare overall and transplant-free survival between sexes. RESULTS: Most
      patients with acetaminophen-induced ALI (68%) or ALF (76%) were women. Higher
      proportions of women than men had psychiatric disease (60% of women vs 48% of
      men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of
      men, P < .01)-more than half of which were opioids. Higher proportions of women
      had severe hepatic encephalopathy (HE) (68% of women vs 58% of men), and required
      intubation (67% of women vs 59% of men, P values <.03). Higher proportions of
      women used vasopressors (26% of women vs 19% of men, P = .04) or mannitol (13% of
      women vs 6% of men, P < .01); proportions of male vs female patients with
      transplant-free survival were similar (68%). On adjusted analysis, women had
      higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35). We
      found a significant interaction between sex and co-ingestion of sedating agents
      (P < .01); co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86;
      95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62; 95% CI, 0.34-1.13; P =
      .12). CONCLUSIONS: In an analysis of the Acute Liver Failure Study Group cohort,
      we found acetaminophen-induced ALI and ALF to be more common among women. Women
      have greater critical care needs than men, and increased risk for severe HE,
      which could be due in part to increased use of sedatives. Future studies should
      investigate sex differences in acetaminophen metabolism and hepatotoxicity,
      particularly among users of opioids.

PMID- 29199147
TI  - Factors Associated With Progression of Barrett's Esophagus: A Systematic Review
      and Meta-analysis.
AB  - BACKGROUND & AIMS: Endoscopic surveillance of patients with Barrett's esophagus
      (BE) is inefficient. Risk stratification of patients might improve the
      effectiveness of surveillance. We performed a systematic review and meta-analysis
      to identify factors associated with progression of BE without dysplasia or BE
      with low-grade dysplasia (LGD) to high-grade dysplasia or esophageal
      adenocarcinoma. METHODS: We performed a systematic search of databases through
      May 2016 to identify cohort studies of patients with baseline BE without
      dysplasia or BE with LGD that reported predictors of progression. Pooled
      estimates (odds ratios) of associations of age, sex, smoking, alcohol use,
      obesity, baseline LGD, segment length, and medication use with progression were
      calculated. RESULTS: We identified 20 studies, reporting 1231 events in 74943
      patients. The studies associated BE progression with increasing age (12 studies;
      odds ratio [OR], 1.03; 95% CI, 1.01-1.05), male sex (11 studies; OR, 2.16; 95%
      CI, 1.84-2.53), ever smoking (current or past, 8 studies; OR, 1.47; 95% CI, 1.09
      1.98), and increasing BE segment length (10 studies; OR, 1.25; 95% CI, 1.16
      1.36), with a low degree of heterogeneity. LGD was associated with a 4-fold
      increase in risk of BE progression (11 studies; OR, 4.25; 95% CI, 2.58-7.0). Use
      of proton pump inhibitors (4 studies; OR, 0.55; 95% CI, 0.32-0.96) or statins (3
      studies; OR, 0.48; 95% CI, 0.31-0.73) were associated with lower risk of BE
      progression. Alcohol use and obesity did not associate with risk of progression.
      CONCLUSIONS: In a systematic review and meta-analysis, we associated older age,
      male sex, smoking, longer BE segment, and LGD with risk of progression of BE.
      Individuals with these features should undergo more intensive surveillance or
      endoscopic therapy. Smoking is a modifiable risk factor for cancer prevention in
      patients with BE.

PMID- 29199149
TI  - Ultra-high mass multimer analysis of protein-1a capping domains by a silicon
      nanomembrane detector.
AB  - Conventional time of flight ion detectors are based on secondary electron
      multipliers encountering a significant loss in detection efficiency, sensitivity
      and resolution with protein mass above 50kDa. In this work we employ a silicon
      nanomembrane detector in a Matrix-Assisted Laser Desorption/Ionization coupled to
      time of flight (MALDI-TOF) mass spectrometer. The operating principle relies on
      phonon-assisted field emission with excellent performance in the high mass range
      from 0.001-2MDa. In addition to the analysis of standard proteins the
      nanomembrane detector (NMD) has the potential for the detection and structural
      investigation of complex macromolecular assemblies through non-covalent
      interactions. In order to investigate this hypothesis, the N-terminal
      capping/methyltransferase domain (CAP) of the Brome Mosaic Virus (BMV) 1a
      replication protein by MALDI-TOF-NMD is analyzed. The signals detected at the
      high m/z-ratios of 912.6/982.7 (*103) and 1333.3 (*103) could be modified species
      of CAP-tricta/tetractamer and the octadecamer. For the first time, the NMD is
      applied to detect biologically complex macromolecular protein assemblies. Hence,
      this technology overcomes the limitations of conventional TOF-detectors and
      increases the analytical range of MALDI-TOF. This technology will be a future
      alternative for the structural analysis of intact virus capsids that will
      complement other MS-based techniques such as native mass spectrometry.

PMID- 29199148
TI  - Do Zones of Hepatic Steatosis Associate With Subtypes and Progression of
      Nonalcoholic Fatty Liver Disease in Children?

PMID- 29199150
TI  - Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel
      salivary biomarkers for early detection of oral squamous cell carcinoma using
      proteomic approaches.
AB  - : No effective screening method is available for oral squamous cell carcinoma
      (OSCC) that is recognized to influence by environmental factors as well as human
      papillomavirus (HPV) and Epstein-Barr virus (EBV). Therefore, we sought to
      identify salivary biomarkers for screening of OSCC with or without HPV and/or EBV
      infection. Saliva, lesion and oral exfoliated cells were collected from OSCC
      patients and cancer-free controls (CFCs) and grouped depending on their HPV- and
      EBV-infection status. Salivary protein was precipitated and subjected to 2
      dimensional gel electrophoresis. Differential expression of proteins was
      identified by mass spectrometry and validated by Western blotting. Distinctive
      expression patterns of salivary proteins were detected in OSCC as compared with
      CFCs. Levels of peroxiredoxin-2 (PRDX-2) and zinc-alpha-2-glycoprotein (ZAG) were
      significantly up-regulated in OSCC cases (p<0.001) relative to CFCs. Similarly,
      these proteins were also up-regulated in lesion cells compared with oral
      exfoliated cells (p<0.001). However, the expression patterns of these proteins
      were not significantly influenced by patient histories (risk factors). In
      combination, these proteins yielded the highest discriminatory power (AUC=0.999),
      sensitivity (100%), and specificity (98.77%) in distinguishing the early stages
      of OSCC. The detection of PRDX-2 combining with ZAG protein could potentially be
      used as salivary biomarkers for early screening of OSCC. SIGNIFICANCE: Our
      findings demonstrate a useful of combined detection of PRDX-2 and ZAG as a
      salivary biomarker for the early detection of OSCC.

PMID- 29199151
TI  - Gender influence on the salivary protein profile of finishing pigs.
AB  - : A study on gender differences in the normal range of biomarkers in porcine
      saliva samples has the scope for further attention. In the present study, the
      salivary protein profiles of age-matched healthy male and female finishing pigs
      were compared. The levels of salivary adenosine deaminase (ADA) activity,
      haptoglobin (Hp) and C-reactive protein (CRP) have been quantified in 32 male and
      32 female pigs to ensure the presence of gender effect on the median levels of
      salivary biomarkers. Moreover, the total salivary protein content was quantified
      and compared. The overall salivary protein distribution was compared with SDS
      PAGE in 14 male and 14 female pigs and the possible gender influence in the
      salivary protein profile was analysed by 2DE in 6 male and 6 female pigs.
      Statistically significant differences were observed in the median values of Hp,
      CRP, and ADA between male and female pigs (p<0.005). Although the total salivary
      protein content was not different between the sexes, the salivary protein
      distribution and profile showed specific gender differences in three proteins of
      the lipocalin family: the odorant-binding protein, salivary lipocalin and
      lipocalin 1. These proteins have been related to animal immune status and should
      be further explored as possible porcine salivary biomarkers. SIGNIFICANCE: The
      biological relevance of the reported research is based on the possible gender
      influence on the discovery of salivary biomarkers in porcine production. As
      differences have been reported in the salivary protein distribution in male pigs
      in comparison to that of female pigs, the normal-range values, according to
      gender, of the newly discovered biomarkers should be explored and defined prior
      to its application in the porcine production system. A hormonal sexual influence
      is highly hypothesized.

PMID- 29199152
TI  - Low level Hg2+ exposure modulates the B-cell cytoskeletal phosphoproteome.
AB  - : Exposure of Wehi-231 B-cells to Hg2+ for 5min resulted in concentration
      dependent changes in protein phosphorylations. Phosphorylation was quantified
      using mass spectrometry to analyze TiO2 and anti-pTyr antibody selected
      phosphopeptides from Wehi-231 digests. The most frequent and largest amplitude
      responses to Hg2+ exposure were increased phosphorylation although a decrease was
      observed for 1% of phosphoproteins detected in the untreated cells. A subset of
      proteins responded with an increase in phosphorylation to Hg2+ exposure at low
      micromolar concentrations. The majority of proteins required Hg2+ over 20MUM in
      order to increase phosphorylation. Ser/Thr phosphorylations are prominent in the
      cytoskeletal organization and the GTPase signaling systems and these systems are
      notable as the primary ones responding to the lowest concentrations of Hg2+.
      Systems that required higher concentrations of Hg2+ to increase phosphorylation
      included immune receptor signaling. The proteins for which an increase in
      phosphorylation occurred at Hg2+ above 20MUM have a higher proportion of pTyr
      sites. Anti Ig stimulation of Wehi-231 cells confirmed that cytoskeletal protein
      phosphorylation and GTPase signaling are modulated in physiologically relevant B
      cell receptor activation. Candidate kinases that respond to Hg2+ exposure at the
      low MUM concentrations include MAP Kinase 1, CaM Kinase II delta and PAK2.
      SIGNIFICANCE: Mercury (Hg) is a wide spread environmental toxicant.
      Epidemiological and laboratory studies suggest that exposure to environmental Hg
      at current levels, which have been perceived to be non-toxic, may contribute to
      immune system dysfunction and autoimmune disease in humans and animals
      respectively. While we have previously shown that exposure of B lymphocytes to
      low levels of mercury interferes with B-cell receptor signaling mediated by post
      transcriptional phosphorylation events, overall the mechanism that is responsible
      for increased autoimmunity in mercury exposed human or animal populations is not
      well understood. The current study evaluated the dose dependent actions of
      mercury to change phosphorylation in the Wehi-231 cell line, an immature B-cell
      model in which actions of mercury on development of cell function can be
      evaluated. The study identified the cytoskeletal proteins as the most sensitive
      to modulation by mercury with changes in Ser/Thr phosphorylation being observed
      at the lowest concentrations of mercury. These findings indicate that the actions
      of mercury on B-cell immune function and development are at least in part likely
      mediated through changes in cytoskeletal protein phosphorylation.

PMID- 29199153
TI  - Retrospective assessment of an assisted reproductive technology method.
AB  - The validation of methods in medical biology is a fundamental step in which the
      laboratory defines its analytical objectives, characterizes the performance of
      the technique according to the level of quality it fixes and discusses the
      results obtained. The objective of this work is to contribute to respect the
      requirements of ISO 15189 in terms of performance verification of a manual
      qualitative technique of medically assisted procreation (PMA): morphological
      identification of the oocyte, the zygote and the embryo, harmonization of
      professional practices and assessment of competences by associating the
      bibliographic approach and above all by justifying its choices. Validation of PMA
      methods is difficult for reasons related to the mostly manual methods used in our
      context but also to the type of matrix i.e. the oocyte sampling which remains a
      valuable harvest. Due to the lack of internal quality control and external
      quality evaluation, risk control in the three pre-, post- and post-analytical
      stages becomes decisive, based on the 5M method, the establishment of coherent
      means of control adapted to its own practice, it also concerns the empowerment of
      staff through training, evaluation and monitoring of operators' performance.

PMID- 29199154
TI  - Leukocytoclastic vasculitis associated with crusted scabies.

PMID- 29199155
TI  - Determination of procalcitonin (PCT) in micro-method on AQT90 FLEX(r) analyzer
      and in vitro stability study.
AB  - Radiometer(r) has developed a point-of-care test for fast PCT measurement on
      whole blood in micromethod on a AQT90 FLEX(r) instrument. We have verified the
      analytical performances of the AQT90 FLEX(r) PCT assay in heparinized macrotube
      and EDTA microtube for pediatric use, according to modified French Society of
      Clinical Biology (SFBC) protocol to the requirements of the standard NF EN ISO
      15189: 2012. The samples (n=61, 30 macrotubes, 31 microtubes) were analyzed by
      the Brahms Kryptor Compact Plus(r) reference method vs the AQT90 FLEX(r). In a
      second step, we studied the stability of the PCT at room temperature for 24 h. A
      good correlation between the two methods on macro- or microtubes is observed
      (respectively r=0.990 and 0.993). The Bland-Altmann representations confirm the
      excellent correlation with a deviant, above the acceptable limit, which was
      calculated according to ISO 5725-6, for each type of tube and for the two
      concentration ranges (lower and greater than 1 ng/mL). The biases observed do not
      affect the clinical decision. No degradation of PCT after 24 h was demonstrated
      by the Mann and Whitney test on macro- and microtubes (p=0.50 and 0.34,
      respectively). The determination of PCT on AQT90 FLEX(r) has satisfactory
      analytical characteristics and can be used as point-of-care testing device on
      whole blood without pre-analytical treatment. In heparinized macrotube and EDTA
      microtube, the PCT is stable at room temperature up to 24 h.

PMID- 29199156
TI  - Consensus Report on Gastroesophageal Reflux Disease in Turkey.

PMID- 29199157
TI  - Method.

PMID- 29199158
TI  - How is the gastroesophageal reflux disease prevalence, incidence, and frequency
      of complications (stricture/esophagitis/Barrett's esophagus/carcinoma) in Turkey
      compared to other geographical regions globally?

PMID- 29199159
TI  - How is gastroesophageal reflux disease classified?
AB  - Gastroesophageal reflux disease (GERD) is one of the most commonly diagnosed
      conditions in the daily practice of gastroenterologists. Due to variations in
      symptoms and clinical findings, differences in the severity of the disease in
      each patient and the fact that diverse methods are used for making a diagnosis
      makes a single and standard classification of this disease impossible. Here a
      step-approach suitable for GERD classification is summarized.

PMID- 29199160
TI  - What is the place of empirical proton pump inhibitor testing in the diagnosis of
      gastroesophageal reflux disease? (Description, duration, and dosage).
AB  - Empirical acid suppression tests that are performed with proton pump inhibitors
      (PPI) are used to detect both the presence of acid-related gastrointestinal
      symptoms and gastroesophageal reflux disease (GERD). In comparison to other
      diagnostic methods, it is non-invasive, easily applicable, and cost-effective in
      the diagnosis of GERD. In addition to typical reflux symptoms, it can also be
      used for diagnostic purposes in patients with non-cardiac chest pain (NCCP). If
      the symptom response is 50% and above when obtained using the PPI test in
      patients with NCCP, it can be considered as positive and the treatment should be
      continued sensitivity of the PPI test in patients with typical symptoms of GERD
      is 27%-89%, while its specificity is 35%-83%. Although there are differences
      related to the duration and dosage of the PPI test, a significant difference has
      not been found according to the type of PPI. When PPI test sensitivity and
      specificity were calculated by cumulatively evaluating the data regarding the PPI
      test in the literature, a sensitivity of 82.3% and specificity of 51.5% was
      obtained. It has been found that high doses of PPI were mostly used in studies,
      and the duration of the median test was 14 days. As a result, the sensitivity of
      PPI trial test is good, but the specificity is low in the diagnosis of GERD in
      patients with typical reflux symptoms.

PMID- 29199161
TI  - Indications of 24-h esophageal pH monitoring, capsule pH monitoring, combined pH
      monitoring with multichannel impedance, esophageal manometry, radiology and
      scintigraphy in gastroesophageal reflux disease?
AB  - Ambulatory esophageal pH monitoring is an essential method in patients exhibiting
      signs of non-erosive reflux disease (NERD) to make an objective diagnosis. Intra
      esophageal pH monitoring is important in patients who are non-responsive to
      medications and in those with extraesophageal symptoms, particularly in NERD,
      before surgical interventions. With the help of the wireless capsule pH
      monitoring, measurements can be made under more physiological conditions as well
      as longer recordings can be performed because the investigation can be better
      tolerated by patients. Ambulatory esophageal pH monitoring can be detected within
      normal limits in 17%-31.4% of the patients with endoscopic esophagitis;
      therefore, normal pH monitoring cannot exclude the diagnosis of gastroesophageal
      reflux disease (GERD). Multi-channel intraluminal impedance pH (MII-pH)
      technology have been developed and currently the most sensitive tool to evaluate
      patients with both typical and atypical reflux symptoms. The sensitivity of a pH
      catheter test is 58% for the detection of acid reflux compared with MII-pH
      monitoring; further, its sensitivity is 28% for the detection of weak acid reflux
      compared with MII-pH monitoring. By adding impedance to pH catheter in patients
      with reflux symptoms, particularly in those receiving PPIs, it has been
      demonstrated that higher rates of diagnoses and symptom analyses can be obtained
      than those using only pH catheter. Esophageal manometry is used in the evaluation
      of patients with functional dysphagia and unexplained noncardiac chest pain and
      prior to antireflux surgery. The use of esophageal manometry is suitable for the
      detection of esophageal motor patterns and extreme motor abnormalities (e.g.,
      achalasia and extreme hypomotility). Esophageal manometry and ambulatory pH
      monitoring are often used in assessments prior to laparoscopic antireflux surgery
      and in patients with reflux symptoms refractory to medical treatment. Although
      the esophageal motility is predominantly normal in patients with non-acid reflux,
      ineffective esophageal motility is often monitored in patients with acid reflux.
      In the literature, there are contradictory and an insufficient number of studies
      regarding radiological methods for the diagnosis of GERD. There are inconsistent
      values for sensitivity and specificity among the barium studies. There are
      inadequate studies in the literature involving scintigraphic examinations in the
      diagnosis of GERD, and a majority of existing studies have been conducted in the
      pediatric group. The results of a few studies do not provide sufficient
      contribution toward the implementation in clinical practice.

PMID- 29199162
TI  - To whom and when the upper gastrointestinal endoscopy is indicated in
      gastroesophageal reflux disease? What is the role of routine esophageal biopsy?
      Which endoscopic esophagitis classification should be used?
AB  - Gastroesophageal reflux disease (GERD) is a chronic disease characterized with
      heartburn and regurgitation symptoms. The prevalence of these symptoms in Turkey
      is reported to be as high as 20%. GERD negatively effects the quality of life
      along with the development of some complications due to chronic course. Upper
      gastrointestinal endoscopy is commonly performed for diagnosis and surveillance
      of complications in the context of GERD. However, there is no consensus in terms
      of timing and indications for endoscopy, use of esophagitis classification
      system, to obtain a biopsy sample or recommendation for surveillance endoscopy.
      In order to answer these questions, we performed a systematic literature search.
      In this article, we report our findings for these targeted questions and our
      proposals as a result of the national consensus program on GERD.

PMID- 29199163
TI  - How should we describe, diagnose and observe the Barrett's esophagus?
AB  - Barrett's esophagus (BE) is one of the major complications of gastroesophageal
      reflux disease (GERD) commonly encountered in gastroenterology clinics. A
      consensus has not been achieved yet with respect to the definition of BE in
      published guidelines. It is advised to use the Prague classification and not to
      use the definition of short and long segments for the endoscopic standardization
      of BE. Undertaking biopsies with white-light endoscopy from each of the 4
      quadrants at 2-cm intervals is the standard method for the diagnosis of BE.
      Because of the ability to perform targeted biopsies, the available data indicate
      that advanced endoscopic techniques may reduce the number of biopsies needed for
      diagnoses. In the presence of severe esophagitis along with BE, the biopsies
      should be taken after 8 weeks of PPI therapy. The evidence values of the
      suggestions about the surveillance requirements and surveillance frequencies are
      low because the available data mostly rely on retrospective studies. We suggest
      that all the patients with BE should be referred to specialized centers for
      surveillance in Turkey. Considering the additional risk factors of the patient,
      endoscopy surveillance intervals of the patients with BE without dysplasia should
      be in a range of 3-5 years and annual surveillance should be made in BE with low
      grade dysplasia. In the presence of BE with high-grade dysplasia (HGD), the
      patients should be referred to specialized centers for treatment within 3 months
      at the latest.

PMID- 29199164
TI  - Does the treatment of proton pump inhibitors reduce dysplasia or adenocarcinoma
      development in Barrett's esophagus?
AB  - Besides reducing the reflux symptoms, the benefit of proton pump inhibitors (PPI)
      in the treatment of Barrett's esophagus (BE) is not exactly known. The data in
      the literature show that although the PPI treatment does not reduce the Barrett's
      segment length, it can reduce dysplasia or the development of early-stage
      adenocarcinoma (odds ratio (OR): 0.46). Therefore, treatments with PPI may be
      considered in patients with a diagnosis of BE and at a high risk of
      adenocarcinoma, even though they are not symptomatic.

PMID- 29199165
TI  - The role of lifestyle changes in gastroesophageal reflux diseases treatment.
AB  - Lifestyle modification has an important role in the treatment of gastroesophageal
      reflux disease (GERD). The development of GERD symptoms with various foods shows
      individual differences. Although there is not enough evidence that certain
      substances in a diet could lead to GERD symptoms, the literature suggests that
      there might be a relationship between reflux development and salt, salted foods,
      chocolate, fatty foods, and fizzy drinks. Because lying on the left side and
      raising the head of the bed in a supine position reduces the development of
      nocturnal reflux symptoms, the head should be elevated for patients with reflux
      symptoms at night, and the patient should lie on the left side. Smoking and
      obesity (especially abdominal) trigger GERD symptoms. Whereas excessive physical
      activity is a significant risk factor for the development of GERD, regular and
      mild-moderate physical activity has been shown to reduce the symptoms of reflux.

PMID- 29199166
TI  - Which drugs are risk factors for the development of gastroesophageal reflux
      disease?
AB  - Gastroesophageal reflux disease (GERD), which is common in many communities, is
      associated with structural factors, eating habits, and the use of certain drugs.
      The use of such drugs can lead to the emergence of GERD and can also exacerbate
      existing reflux symptoms. These drugs can contribute to GERD by directly causing
      mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by
      affecting esophagogastric motility. In this article, we report our investigation
      of the relationships between GERD and medications within the scope of the
      "Turkish GERD Consensus Group." For the medication groups for which sufficient
      data were obtained (Figure 1), a systematic literature review in English was
      conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti
      inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH
      Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All
      Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All
      Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields]
      and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH
      Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields],
      "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH
      Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms],
      "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms],
      "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and
      "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and
      "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms]
      and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND
      "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results
      are presented here.

PMID- 29199167
TI  - Which diseases are risk factors for developing gastroesophageal reflux disease?
AB  - Although the pathophysiology of gastroesophageal reflux disease (GERD) remains
      unclear, it is accepted as a multifactorial disease. It is thought that some of
      the interventions that might cause alterations in the normal gastrointestinal
      tract anatomy and diseases that affect the lower esophageal sphincter, esophageal
      clearance, and stomach motility (gastric emptying) might lay a foundation for
      GERD development. Moreover, it is common knowledge that GERD might cause various
      extraesophageal symptoms and complications. A possible connection between GERD
      and sarcoidosis, amyloidosis, hypothyroidism, rheumatoid arthritis, mixed
      connective tissue disorders, Sjogren's syndrome, systemic sclerosis, diabetes
      mellitus, cholecystectomy, sleeve gastrectomy, sleep apnea syndrome, chronic
      obstructive pulmonary disease, and asthma were summarized in this literature
      review.

PMID- 29199168
TI  - Medical treatment of gastroesophageal reflux disease.
AB  - Proton pump inhibitors (PPIs) are the most effective agents in the first-line and
      maintenance treatment of gastroesophageal reflux disease. As the grade of
      esophagitis increases, an increase is also observed in the level of endoscopic
      response to PPIs. In the first-line therapy of patients with severe esophagitis
      (Los Angeles (LA) Grade C-D), administration of a standard dose of PPIs bid has
      been reported to be more beneficial than PPIs qd. While any intermittant and low
      dose-continuous treatment can be chosen for the maintenance therapy of patients
      with non-erosive reflux disease or mild esophagitis (LA Grade A-B), continuous
      use of a standard dose of PPIs is preferred in the maintenance therapy of
      patients with severe esophagitis (LA Grade C-D). In patients who use PPIs for a
      long time, the drug must be stopped by gradually decreasing the dose.

PMID- 29199142
TI  - High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn's
      Disease.
AB  - BACKGROUND & AIMS: Little is known about the magnitude of the risk of anal and
      rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to
      assess the risk of anal and rectal cancer in patients with Crohn's perianal
      disease followed up in the Cancers Et Surrisque Associe aux Maladies
      Inflammatoires Intestinales En France (CESAME) cohort. METHODS: We collected data
      from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the
      observational CESAME study in France, from May 2004 through June 2005; 14.9% of
      participants had past or current anal and/or perianal Crohn's disease. Subjects
      were followed up for a median time of 35 months (interquartile range, 29-40 mo).
      To identify risk factors for anal cancer in the total CESAME population, we
      performed a case-control study in which participants were matched for age and
      sex. RESULTS: Among the total IBD population, 8 patients developed anal cancer
      and 14 patients developed rectal cancer. In the subgroup of 2911 patients with
      past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed
      anal squamous-cell carcinoma, 3 developed perianal fistula-related
      adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates
      were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000
      patient-years for perianal fistula-related adenocarcinoma, and 0.77 per 1000
      patient-years for rectal cancer. Among the 16,575 patients with ulcerative
      colitis or Crohn's disease without anal or perianal lesions, the incidence rate
      of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per
      1000 patient-years. Among factors tested by univariate conditional regression
      (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence
      of past or current anal and/or perianal lesions), the presence of past or current
      anal and/or perianal lesions at cohort entry was the only factor significantly
      associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18
      551.51; P = .03). CONCLUSIONS: In an analysis of data from the CESAME cohort in
      France, patients with anal and/or perianal Crohn's disease have a high risk of
      anal cancer, including perianal fistula-related cancer, and a high risk of rectal
      cancer.

PMID- 29199169
TI  - Treatment of reflux disease during pregnancy and lactation.
AB  - Gastroesophageal reflux disease (GERD) is frequently seen during pregnancy. In
      the medical treatment of pregnant women with GERD, alginic acid and sucralfate
      can be used. Calcium- and magnesium-based antacids can also be used, particularly
      for patients with preeclampsia. In particular, ranitidine -a histamine-2 receptor
      blocker- is preferred. In the case of non-responsiveness to the abovementioned
      treatments, proton pump inhibitors (PPIs), except omeprazole, can be given
      considering the benefit-harm ratio for the mother and fetus after the first
      trimester. In cases with GERD during the lactation period, drugs having minimum
      systemic absorption, such as sucralfate and alginic acid, are preferable but
      there is no data.

PMID- 29199171
TI  - Gastroesophageal reflux disease and the relationship with Helicobacter pylori.
AB  - After Helicobacter pylori was identified, and its relationship with peptic ulcer
      disease was exactly shown, the relationship of this bacterium with
      gastroesophageal reflux disease (GERD) gained momentum and discussions continue
      to this day. We reviewed the literature for the relationship between H. pylori
      and GERD. According to the existing data, there is no relationship between GERD
      and H. pylori presence. Successful eradication therapy does not have an impact on
      the emergence or exacerbation of GERD. However Barrett's esophagus and esophageal
      adenocarcinoma are less frequent, especially in the presence of CagA positive H.
      pylori infections. Long-term use of proton pump inhibitor (PPI) may have an
      impact on the development of atrophy and/or intestinal metaplasia in H. pylori
      positive patients; therefore, H. pylori eradication is recommended in patients
      that should use long-term PPI. As a conclusion, H. pylori screening and the
      eradication decision should be independent of GERD, except for patients that will
      use long-term PPI.

PMID- 29199170
TI  - What is the long term acid inhibitor treatment in gastroesophageal reflux
      disease? What are the potential problems related to long term acid inhibitor
      treatment in gastroesophageal reflux disease? How should these cases be followed?
AB  - The meta-analyses of observational studies (OBS) showed the risk of any fracture
      and hip fracture slightly increased with proton pump inhibitor (PPI) treatment
      depending on the dose and regardless of time. This was not observed with
      histamine-2 receptor antagonists (H2RA). The risk of bacterial overgrowth and
      spontaneous bacterial peritonitis were increased with PPI therapy, but not with
      H2RA. In meta-analyses of OBS, a slight increase was observed in the risk of
      community-acquired pneumonia (CAP) in the early stages (<1 month) of PPI use and
      particularly at high doses. In a five-year LOTUS study, no difference was found
      in vitamin B12, folic acid, vitamin D, and calcium values in terms of the initial
      and end of follow-up levels. No increase in the risk of premalignant gastric
      lesions was observed in the meta-analysis of RCTs in which PPI treatment (>=6
      months) was given to Helicobacter pylori negative patients. The risk of
      hypomagnesemia with PPI use was increased in patients having GFR<60, using
      diuretics, and over 65 years of age. Quasi-experimental studies showed a reduced
      zinc absorption with PPI use. In the meta-analysis of OBS, long-term (>1 year)
      PPI use increased the risk of fundic polyps, but no risk was found in shorter
      use. The meta-analyses of RCTS showed no difference between PPI and surgery or
      placebo arms and between the arms of H2RA and placebo in terms of all side
      effects. No difference was found between the PPI and H2RA arms both in all and
      serious adverse effects.

PMID- 29199172
TI  - When proton pump inhibitors are compared, are there specific cases in which a
      certain proton pump inhibitors should be particularly preferred?
AB  - Currently, proton pump inhibitors (PPIs) are widely used either over the counter
      or on prescription drugs. PPI's are frequently used with other drugs when elderly
      and chronic desease burden population is taken to consideration. Drug
      interactions with PPIs are a prominent clinical problem in this direction. In
      this study, we reviewed potential risks of concomittant use of PPIs and other
      drugs and apropriate PPI choise.

PMID- 29199173
TI  - What is proton pump inhibitors unresponsiveness in gastroesophageal reflux
      disease? How should these cases be managed?
AB  - Proton pump inhibitors become the most potent therapeutic option in
      gastroesophageal reflux disease. Unresponsiveness to this treatment is not
      uncommon in clinical practice. We reviewed the definition of PPI unresponsiveness
      and the management of this situation.

PMID- 29199174
TI  - Endometrioma of the sigmoid colon presenting with intestinal obstruction.

PMID- 29199175
TI  - Author's Reply.

PMID- 29199176
TI  - Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three
      Different First-Line Treatment Modalities in the Last Two Decades: A Single
      Center Experience.
AB  - OBJECTIVE: In this study, we retrospectively analyzed the clinical outcome,
      treatment responses, infectious complications, and survival rates of 71 hairy
      cell leukemia (HCL) cases. MATERIALS AND METHODS: Sixty-seven patients received a
      first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was
      administered in 31 cases, 19 patients received interferon-alpha (INF-alpha),
      splenectomy was performed in 16 cases, and rituximab was used in one. RESULTS:
      Although the highest overall response rate (ORR) was observed in patients
      receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-alpha, and
      splenectomy subgroups. Relapse rates were significantly lower in patients who
      received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA
      was significantly higher than in patients with INF-alpha and splenectomy, but we
      found similar overall survival rates with all three upfront treatment modalities.
      Infections including tuberculosis were a major problem. CONCLUSION: Although
      purine analogues have improved the ORRs and PFS, there is still much progress to
      make with regard to overall survival and relapsed/refractory disease in patients
      with HCL.

PMID- 29199177
TI  - Inhibition of glycogen phosphorylase stimulates ventromedial hypothalamic nucleus
      AMP-activated protein kinase: Activity and neuronal nitric oxide synthase protein
      expression in male rats.
AB  - The glucose polymer glycogen is a vital fuel reserve in the brain. The mediobasal
      hypothalamic energy sensor AMP-activated protein kinase (AMPK) maintains
      glucostasis via neurotransmitter mechanisms that suppress [gamma-aminobutyric
      acid; GABA] or stimulate [nitric oxide; steroidogenic factor-1 (SF1)] counter
      regulatory outflow. This study investigated whether glycogen-derived fuel supply
      is a critical screened variable in ventromedial hypothalamic nucleus (VMN)
      monitoring of neuro-metabolic stability during glucostasis and/or insulin (I)
      induced hypoglycemia. Adult male rats were pretreated by intra-VMN infusion of
      the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)
      before sc vehicle or I injection. Western blot analyses of micropunch-dissected
      VMN tissue from euglycemic animals showed DAB augmentation of phosphoAMPK
      (pAMPK), neuronal nitric oxide synthase (nNOS), and SF-1, but not glutamate
      decarboxylase65/67 (GAD) protein. Combinatory DAB/I treatment did not further
      enhance AMPK activity but significantly amplified nNOS expression relative to DAB
      alone. Hypoglycemic stimulation of corticosterone, but not glucagon release was
      prevented by DAB Results imply that glycogen-derived substrate fuel provision
      represses VMN AMPK activity and neurotransmitter signals of metabolic deficiency.
      Progressive augmentation of nNOS protein by DAB/I versus DAB/V intimates that
      "fuel-inhibited" nitrergic neurons may exhibit increasing sensitivity to
      disrupted glycogen breakdown during glucoprivation versus glucostasis. nNOS and
      GAD reactivity to DAB/I, but not I implies that acute glycogen utilization during
      hypoglycemia may be sufficiently robust to avert effects on local metabolic
      sensory signaling. DAB/I upregulation of GAD alongside prevention of
      hypercorticosteronemia suggests that indicators of metabolic sufficiency may
      occur secondary to local compensatory adaptations to severe restriction of
      glucose-derived energy.

PMID- 29199178
TI  - Carbonic anhydrase 2-like in the giant clam, Tridacna squamosa: characterization,
      localization, response to light, and possible role in the transport of inorganic
      carbon from the host to its symbionts.
AB  - The fluted giant clam, Tridacna squamosa, lives in symbiosis with zooxanthellae
      which reside extracellularly inside a tubular system. Zooxanthellae fix inorganic
      carbon (Ci) during insolation and donate photosynthate to the host. Carbonic
      anhydrases catalyze the interconversion of CO2 and HCO3-, of which carbonic
      anhydrase 2 (CA2) is the most ubiquitous and involved in many biological
      processes. This study aimed to clone a CA2 homolog (CA2-like) from the fleshy and
      colorful outer mantle as well as the thin and whitish inner mantle of T.
      squamosa, to determine its cellular and subcellular localization, and to examine
      the effects of light exposure on its gene and protein expression levels. The cDNA
      coding sequence of CA2-like from T. squamosa comprised 789 bp, encoding 263 amino
      acids with an estimated molecular mass of 29.6 kDa. A phenogramic analysis of the
      deduced CA2-like sequence denoted an animal origin. CA2-like was not detectable
      in the shell-facing epithelium of the inner mantle adjacent to the extrapallial
      fluid. Hence, CA2-like is unlikely to participate directly in light-enhanced
      calcification. By contrast, the outer mantle, which contains the highest density
      of tertiary tubules and zooxanthellae, displayed high level of CA2-like
      expression, and CA2-like was localized to the tubule epithelial cells. More
      importantly, exposure to light induced significant increases in the protein
      abundance of CA2-like in the outer mantle. Hence, CA2-like could probably take
      part in the increased supply of inorganic carbon (Ci) from the host clam to the
      symbiotic zooxanthellae when the latter conduct photosynthesis to fix Ci during
      light exposure.

PMID- 29199179
TI  - On the relationship between glucose absorption and glucose-stimulated secretion
      of GLP-1, neurotensin, and PYY from different intestinal segments in the rat.
AB  - Ingested glucose powerfully stimulates the secretion of appetite- and metabolism
      regulating peptide hormones from the gut - including glucagon-like peptide-1 (GLP
      1), neurotensin (NT), and polypeptide YY (PYY). However, the regional origin of
      these secretions after glucose stimulation is not well characterized, and it
      remains uncertain how their secretion is related to glucose absorption. We
      isolated and perfused either the upper (USI) or the lower (LSI) small intestine
      or the colon from rats and investigated concomitant glucose absorption and
      secretory profiles of GLP-1, NT, and PYY In the USI and LSI luminal glucose (20%,
      w/v) increased GLP-1 and NT secretion five to eightfold compared to basal
      secretion. Compared to the USI, basal and stimulated GLP-1 secretion from the
      colon was 8-10 times lower and no NT secretion was detected. Luminal glucose
      stimulated secretion of PYY four to fivefold from the LSI and from the USI and
      colon, but the responses in the USI and colon were 5- to 15-fold lower than in
      the LSI Glucose was absorbed to a comparable extent in the USI and LSI by
      mechanisms that partly depended on both SGLT1 and GLUT2 activity, whereas the
      absorption in the colon was 80-90% lower. The absorption rates were, however,
      similar when adjusted for segmental length. Glucose absorption rates and NT, PYY
      and in particular GLP-1 secretion were strongly correlated (P < 0.05). Our
      results indicate that the rate of secretion of GLP-1, NT, and PYY in response to
      glucose, regardless of the involved molecular machinery, is predominantly
      regulated by the rate of glucose absorption.

PMID- 29199183
TI  - Letter from the Editor.

PMID- 29199180
TI  - Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress
      in C2C12 myotubes: Impact on muscle atrophy.
AB  - Lipid accumulation in skeletal muscle results in dysregulation of protein
      metabolism and muscle atrophy. We previously reported that treating C2C12
      myotubes with palmitate (PA), a saturated fatty acid, increases the overall rate
      of proteolysis via activation of the ubiquitin-proteasome and autophagy systems;
      co-treatment with the omega-3 polyunsaturated fatty acid docosahexaenoic acid
      (DHA) prevents the PA-induced responses. Others have reported that PA induces
      endoplasmic reticulum (ER) stress which initiates the unfolded protein response
      (UPR), a collective group of responses that can lead to activation of caspase
      mediated proteolysis and autophagy. Presently, we tested the hypothesis that DHA
      protects against PA-induced ER stress/UPR and its atrophy-related responses in
      muscle cells. C2C12 myotubes were treated with 500 MUmol/L PA and/or 100 MUmol/L
      DHA for 24 h. Proteins and mRNA associated with ER stress/UPR, autophagy, and
      caspase-3 activation were evaluated. PA robustly increased the phosphorylation of
      protein kinase R (PKR)-like ER kinase (PERK) and eukaryotic initiation factor
      2alpha (eIF2alpha). It also increased the mRNAs encoding activating transcription
      factor 4 (ATF4), spliced X-box binding protein 1 (XBP1s), C/EBP homologous
      protein (CHOP), and autophagy-related 5 (Atg5) as well as the protein levels of
      the PERK target nuclear factor erythroid 2-related factor (Nrf2), CHOP, and
      cleaved (i.e., activated) caspase-3. Co-treatment with DHA prevented all of the
      PA-induced responses. Our results indicate that DHA prevents PA-induced muscle
      cell atrophy, in part, by preventing ER stress/UPR, a process that leads to
      activation of caspase-mediated proteolysis and an increase in expression of
      autophagy-related genes.

PMID- 29199181
TI  - Takeaway meal consumption and risk markers for coronary heart disease, type 2
      diabetes and obesity in children aged 9-10 years: a cross-sectional study.
AB  - OBJECTIVE: To investigate associations between takeaway meal consumption and risk
      markers for coronary heart disease, type 2 diabetes and obesity risk markers in
      children. DESIGN: A cross-sectional, school-based observational study. SETTING:
      85 primary schools across London, Birmingham and Leicester. PARTICIPANTS: 1948 UK
      primary school children in year 5, aged 9-10 years. MAIN OUTCOME MEASURES:
      Children reported their frequency of takeaway meal consumption, completed a 24
      hour dietary recall, had physical measurements and provided a fasting blood
      sample. RESULTS: Among 1948 participants with complete data, 499 (26%)
      never/hardly ever consumed a takeaway meal, 894 (46%) did so <1/week and 555
      (28%) did >=1/week. In models adjusted for age, sex, month, school, ethnicity and
      socioeconomic status, more frequent takeaway meal consumption was associated with
      higher dietary intakes of energy, fat % energy and saturated fat % energy and
      higher energy density (all P trend <0.001) and lower starch, protein and
      micronutrient intakes (all P trend <0.05). A higher frequency of takeaway meal
      consumption was associated with higher serum total cholesterol and low-density
      lipoprotein (LDL) cholesterol (P trend=0.04, 0.01, respectively); children eating
      a takeaway meal >=1/week had total cholesterol and LDL cholesterol 0.09 mmol/L
      (95% CI 0.01 to 0.18) and 0.10 mmol/L (95% CI 0.02 to 0.18) higher respectively
      than children never/hardly ever eating a takeaway meal; their fat mass index was
      also higher. CONCLUSIONS: More frequent takeaway meal consumption in children was
      associated with unhealthy dietary nutrient intake patterns and potentially with
      adverse longer term consequences for obesity and coronary heart disease risk.

PMID- 29199184
TI  - Home-based vibration assisted exercise as a new treatment option for scoliosis -
      A randomised controlled trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of scoliosis
      specific exercises (SSE) on a side-alternating whole body vibration platform
      (sWBV) as a home-training program in girls with adolescent idiopathic scoliosis
      (AIS). METHODS: 40 female AIS patients (10-17 years) wearing a brace were
      randomly assigned to two groups. The intervention was a six months, home-based,
      SSE program on a sWBV platform five times per week. Exercises included standing,
      sitting and kneeling. The control group received regular SSE (treatment as
      usual). The Cobb angle was measured at start and after six months. Onset of
      menarche was documented for sub-group analysis. RESULTS: The major curve in the
      sWBV group decreased significantly by -2.3 degrees  (SD+/-3.8) (95% CI -4.1 to 
      0.5; P=0.014) compared to the difference in the control group of 0.3 degrees 
      (SD+/-3.7) (95% CI -1.5 to 2.2; P=0.682) (P=0.035). In the sWBV group 20% (n=4)
      improved, 75% (n=15) stabilized and 5% (n=1) deteriorated by >=5 degrees . In the
      control group 0% (n=0) improved, 89% (n=16) stabilized and 11% (n=2)
      deteriorated. The clinically largest change was observed in the 'before-menarche'
      sub-group. CONCLUSIONS: Home-based SSE combined with sWBV for six months
      counteracts the progression of scoliosis in girls with AIS; the results were more
      obvious before the onset of the menarche.

PMID- 29199185
TI  - Efficacy and safety of whole body vibration in maintenance hemodialysis patients 
      A pilot study.
AB  - OBJECTIVES: The aim of this study was to assess safety and effectiveness of Whole
      Body Vibration exercise (WBV) to improve physical performance and parameters of
      inflammation in patients on maintenance hemodialysis (MHD). METHODS: Prospective,
      open-label trial in n=14 patients on maintenance hemodialysis. Participants
      performed WBV twice weekly for 12 weeks before (n=8) or after (n=6) hemodialysis
      sessions. The primary endpoint was physical performance assessed by the Short
      Physical-Performance-Battery (SPPB). Secondary endpoints included established
      parameters of musculoskeletal assessment and blood chemistry. RESULTS: As
      compared to baseline, physical performance (SPPB) improved significantly
      (p=0.035). Moderate advances were also seen for 6-Minute-Walking test, Timed-up
      and-go test, jumping height and handgrip strength. Improvements were particularly
      pronounced in subjects with seriously impaired baseline performance. Skeletal
      muscle index showed a tendency to better values. Laboratory data exhibited a
      significant reduction of white blood cell count and a trend to lower levels of
      hsCRP. WBV was generally well tolerated. Two events of clinically significant
      blood pressure decline occurred in patients exercising after dialysis sessions.
      CONCLUSIONS: Results of this pilot study suggest effectiveness and safety of WBV
      in hemodialysis patients. Beneficial effects may affect both, parameters of
      physical performance and systemic inflammatory activity, which should be verified
      in larger scale clinical trials.

PMID- 29199186
TI  - Neural adaptations after short-term wingate-based high-intensity interval
      training.
AB  - OBJECTIVES: This study examined the neural adaptations associated with a low
      volume Wingate-based High Intensity Interval Training (HIIT). METHODS: Fourteen
      recreationally trained males were divided into an experimental (HIIT) and a
      control group to determine whether a short-term (4 weeks) Wingate-based HIIT
      program could alter the Hoffmann (H-) reflex, volitional (V-) wave and maximum
      voluntary contraction (MVC) of the plantar-flexor muscles, and the peak power
      achieved during a Wingate test. RESULTS: Absolute and relative peak power
      increased in the HIIT group (ABS_Ppeak: +14.7%, P=0.001; and REL_Ppeak: +15.0%,
      P=0.001), but not in the control group (ABS_Ppeak: P=0.466; and REL_Ppeak:
      P=0.493). However, no significant changes were found in the MVC (P>0.05 for both
      groups). There was a significant increase in H-reflex size after HIIT (+24.5%,
      P=0.004), while it remained unchanged in the control group (P=0.134). No
      significant changes were observed either in the V-wave or in the Vwave/Mwave
      ratio (P>0.05 for both groups). CONCLUSION: The Wingate-based training led to an
      increased peak power together with a higher spinal excitability. However, no
      changes were found either in the volitional wave or in the MVC, indicating a lack
      of adaptation in the central motor drive.

PMID- 29199187
TI  - Decomposition of three-dimensional ground-reaction forces under both feet during
      gait.
AB  - : Three-dimensional ground reaction forces (3D-GRF) are essential for functional
      evaluation for rehabilitation. A platform path is required to obtain the 3D-GRF.
      The main shortcoming of these platform paths is that during double stance phases
      of gait, both feet can be placed on the same force platform causing the need for
      decomposing the 3D-GRF under each foot. Despite the high number of studies on
      force decomposition, there is still no method on the decomposition of 3D-GRF
      based on data from platforms. OBJECTIVE: This study aims to present an automatic
      method using parametric curve fitting modeling to increase the accuracy of
      decomposition of 3D-GRF during double stances under each foot. METHODS: The
      decomposition method was applied to the global 3D-GRF using 3rd order polynomial,
      sine, and sine-sigmoid functions. The computed 3D-GRF was compared to the 3D-GRF
      independently recorded by force platforms for each subject. RESULTS: The relative
      average error between the computed 3D-GRF and the recorded 3D-GRF were equal to
      3.3+/-1.6%. In details for the vertical, antero-posterior, and medio-lateral GRF,
      these errors were 2.9+/-1.6%, 6.3+/-4.3%, and, 9.5+/-3.6%, respectively, for 30
      subjects. CONCLUSION: The global error on the GRF is the best one in the
      literature. This method can be validated on various populations with
      musculoskeletal disorders.

PMID- 29199190
TI  - Fanconi syndrome in the adulthood. The role of early diagnosis and treatment.

PMID- 29199188
TI  - Cost-effective osteoporosis treatment thresholds for people living with HIV
      infection in Greece.
AB  - OBJECTIVES: We aimed to specifically define the FRAX-based cost-effective
      treatment thresholds for osteoporosis among people living with HIV (PLWHIV) in
      Greece and to compare them with those of the general population. METHODS: A
      previously described state transition Markov cohort model was used in order to
      estimate the cost-effective intervention thresholds for osteoporotic therapy
      among Greek PLWHIV employing the FRAX(r) tool. The model-derived relative risk at
      which an incremental cost-effectiveness ratio of 30,000?/QALY gained was observed
      for treatment versus no intervention was multiplied by the average Greek FRAX
      based 10-year probabilities for both major osteoporotic and hip fractures.
      RESULTS: There exists no significant difference in the cost-effective FRAX(r)
      based thresholds between PLWHIV and general population. The absolute 10-year
      probabilities of 2.5 and 10% for hip and major osteoporotic fractures,
      respectively, could be used for the initiation of treatment for PLWHIV of both
      genders under the age of 75; for older subjects the proposed intervention
      threshold is raised to 5 and 15% 10-year probability for hip and major
      osteoporotic fracture, respectively. CONCLUSIONS: Our study confirms the general
      recommendation for the use of country specific FRAX(r) thresholds when managing
      bone fragility within PLWHIV. In any case, clinical judgment and appropriate
      screening are mandatory and irreplaceable.

PMID- 29199189
TI  - Biomechanical study on different lengths of PFNA fixation for unstable
      intertrochanteric femoral fractures.
AB  - OBJECTIVE: The aim of our study was to compare the biomechanical stability of the
      Proximal Femoral Nail Antirotation (PFNA) (with 200 mm, 240 mm and 280 mm-long
      main nails) for the management of unstable intertrochanteric femoral fractures.
      METHODS: Tronzo-Evans Type IV and V fractures were built by applying a three
      dimensional finite element model. Further, PFNA-II with 200 mm, 240 mm and 280 mm
      long main nails were applied for fixation. The above model is the creation of 3
      researchers designed in order to obtain average values of numerical stress. Von
      Mises stress distribution and medial and lateral stress peak of the femur and
      PFNA were compared. RESULTS: 240 mm and 280 mm PFNA medial stress peak was
      reduced significantly in comparison to 200 mm PFNA (p?0.05). However, there was
      no difference between 240 mm and 280 mm PFN. Also, no statistical difference was
      observed with any of 3 lengths in both medial and lateral stress peak for Evans
      Type IV and V PFNA. CONCLUSION: 240 mm and 280 mm PFNA could reduce femur
      fixation medial stress peak. Further, they were more efficient in comparison to
      the 200 mm PFNA, and their biomechanical stability was similar to that of the 280
      mm nail.

PMID- 29199191
TI  - An animal model of reconstruction of single femoral tunnel with single bone bi
      quadruple ACL and internal fixation.
AB  - We introduced several variables in an animal model of anterior cruciate ligament
      (ACL) reconstruction to determine the best parameters for surgery in humans. We
      divided 130 LYD pigs into two groups depending on whether the femoral tunnel goes
      through the medial tibial tunnel or through the medial fossa of the knee joint.
      Each subgroup was further divided. Four weeks after surgery the knee specimens
      were examined for passive flexion and extension test. No group showed a creep
      effect. In the biomechanical tests, we recorded maximal strength, maximum load,
      and stiffness parameters. The 100 degrees  + 1.0 mm, 1.5 mm, and 2.0 mm positions
      of the tibial tunnel group, and 10.5 (1.5) + 1.0 mm, 1.5 mm, and 2.0 mm positions
      of the knee joint cavity group had better biomechanical effects,
      histocompatibility and revascularization in ACL reconstruction. Overall, these
      results demonstrated significant differences in the effectiveness of ACL
      reconstruction based on several surgical parameters, which should contribute to
      establishing a gold standard for ACL surgery in patients.

PMID- 29199192
TI  - Alterations to maternal cortical and trabecular bone in multiparous middle-aged
      mice.
AB  - OBJECTIVES: During the reproductive cycle, altered calcium homeostasis is
      observed due to variable demand for mineral requirements. This results in
      increased bone resorption during the time period leading up to parturition and
      subsequent lactation. During lactation, women will lose 1-3% of bone mineral
      density per month, which is comparable to the loss experienced on an annual basis
      post-menopausal. The purpose of this study was to determine the effect of parity
      on bone formation in middle-aged mice. METHODS: Mice were mated and grouped by
      number of parity and compared with age matched nulliparous controls. Measurements
      were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline
      phosphatase levels were also measured. RESULTS: An increase in trabecular bone
      mineral density was observed when comparing mice that had undergone parity once
      to the nulliparous control. An overall decrease in trabecular bone mineral
      density was observed as parity increased from 1 to 5 pregnancies. No alteration
      was seen in cortical bone formation. No difference was observed when calcium,
      protein and alkaline phosphatase levels were assessed. CONCLUSIONS: This study
      demonstrates that number of parity has an impact on trabecular bone formation in
      middle-aged mice, with substantial changes in bone density seen among the parous
      groups.

PMID- 29199193
TI  - Effect of virtual reality versus conventional physiotherapy on upper extremity
      function in children with obstetric brachial plexus injury.
AB  - OBJECTIVES: The objective was to evaluate the effects of virtual reality versus
      conventional physiotherapy on upper extremity function in children with obstetric
      brachial plexus injury. METHODS: Forty children with Erb's palsy were selected
      for this randomized controlled study. They were assigned randomly to either group
      A (conventional physiotherapy program) or group B (virtual reality program using
      Armeo(r) spring for 45 min three times/week for 12 successive weeks). Mallet
      system scores for shoulder function and shoulder abduction, and external rotation
      range of motion (ROM) were obtained; shoulder abductor, and external rotators
      isometric strength were evaluated pre-and post-treatment using Mallet scoring
      system, standard universal goniometer, and handheld dynamometer. RESULTS: The
      results of this study indicate that the children in both groups showed
      improvement in shoulder functions post-treatment with greater improvements in
      group B. The abduction muscle strength after treatment was 8.53 and 11.3 Nm for
      group A and group B, respectively. The external rotation muscle strength after
      treatment was 5.88 and 7.45 Nm for group A and group B, respectively.
      CONCLUSIONS: The virtual reality program is a significantly more effective than
      conventional physiotherapy program in improving the upper extremity functions in
      children with obstetric brachial plexus injury.

PMID- 29199194
TI  - Relationship between sleep and muscle strength among Chinese university students:
      a cross-sectional study.
AB  - OBJECTIVES: Poor sleep quality and short sleep duration are associated with an
      increased risk for muscle mass reduction. Thus, they may also influence muscle
      strength. This study aimed to investigate the association between sleep quality
      and duration, and muscle strength in university students. METHODS: This cross
      sectional study comprised 10,125 university students aged 16-30 years. Handgrip
      strength was measured using a handheld digital dynamometer. Sleep quality and
      duration were measured using a self-reported questionnaire. RESULTS: After
      adjusting for confounding factors, a positive association between sleep quality
      and muscle strength was observed in both male and female students. Moreover, men
      with shorter sleep duration (?6 hours) had poorer muscle strength than that of
      men who slept for 7-8 hours and over 8 hours in the final adjusted model. There
      was no significant difference in the association of sleep duration and muscle
      strength between men who slept 7-8 hours and those who slept for more than 8
      hours. No significant association was observed between sleep duration and muscle
      strength in female students. CONCLUSIONS: Good sleep quality is associated with
      greater muscle strength, while short sleep duration may be a risk factor for
      decreased muscle strength in university students.

PMID- 29199195
TI  - Effect of weight bearing exercise to improve bone mineral density in children
      with cerebral palsy: a meta-analysis.
AB  - BACKGROUND: Despite widespread clinical use of weight bearing exercises to manage
      low bone mineral density (BMD) in children and adolescents with cerebral palsy
      (CP), previous studies have reported heterogeneous results on the effect of
      weight bearing exercise on BMD. PURPOSE: We performed the current meta-analysis
      to assess the effects of weight bearing exercise on increasing BMD in children
      who have CP with low BMD. MATERIALS AND METHODS: We searched PubMed, Cochrane,
      and Embase from inception through to October 2016 for studies that aims to
      investigate the effect of weight bearing exercise on BMD in children with CP.
      Following the searching result, the 118 relevant studies were reviewed and
      undergone selection process. Standardized mean difference (SMD), 95% confidence
      intervals (CIs) and p-values were calculated for analysis. RESULTS: Three studies
      were ultimately included in the meta-analysis: one randomized-controlled study
      and two case-controlled studies. No significant difference was observed in the
      BMD of the lumbar spine between before treatment and after treatment (SMD,0.341;
      95% CI,-0.647-1.330; p=0.449) but the BMD of the femur significantly improved
      after applying weight bearing exercise compared to pre-treatment values (SMD,
      0.916; 95% CI, 0.382-1.114; p?0.001). CONCLUSIONS: Weight bearing exercise has a
      significant effect on improving BMD of the femur in children with CP.

PMID- 29199197
TI  - Abstracts of the 2017 International Workshop on Musculoskeletal and Neuronal
      Interactions.

PMID- 29199196
TI  - Effect of different head-neck-jaw postures on cervicocephalic kinesthetic sense.
AB  - OBJECTIVES: To investigate the effect of different induced head-neck-jaw postures
      on head-neck relocation error among healthy subjects. METHODS: 30 healthy adult
      male subjects participated in this study. Cervicocephalic kinesthetic sense was
      measured while standing, habitual sitting, habitual sitting with clenched jaw and
      habitual sitting with forward head posture during right rotation, left rotation,
      flexion and extension using kinesthetic sensibility test. RESULTS: Head-neck
      relocation error was least while standing, followed by habitual sitting, habitual
      sitting with forward head posture and habitual sitting with jaw clenched.
      However, there was no significant difference in error between different tested
      postures during all the movements. CONCLUSIONS: To the best of our knowledge,
      this is the first study to see the effect of different induced head-neck-jaw
      postures on head-neck position sense among healthy subjects. Assuming a posture
      for a short duration of time doesn't affect head-neck relocation error in normal
      healthy subjects.

PMID- 29199200
TI  - Age Stratification and Impact of Eicosapentaenoic Acid and Docosahexaenoic Acid
      to Arachidonic Acid Ratios in Ischemic Stroke Patients.
AB  - AIM: We focused on the ratios of eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) to arachidonic acid (AA) and explored the significance of these ratios
      relative to clinical characteristics by age in ischemic stroke patients. METHODS:
      We enrolled patients with acute ischemic stroke who underwent radiological
      investigations and laboratory examinations, including measurement of serum EPA,
      DHA, and AA levels, and controls. Patients were classified according to age (<65,
      65-74, and >= 75 years) and the tertile of EPA/AA and DHA/AA ratios, and clinical
      aspects were compared with these factors. RESULTS: We analyzed 373 patients (age
      70.2+/-13.4 years; 245 males) and 105 controls. Among stroke patients, patients
      aged <65 years had the lowest EPA/AA (0.35+/-0.23, p=0.006) and DHA/AA (0.73+/
      0.27, p<0.001) ratios. Compared with controls, patients aged <65 years showed
      lower EPA/AA (vs. 0.49+/-0.25, p<0.001) and DHA/AA (vs. 0.82+/-0.26, p=0.009)
      ratios. From logistic regression analysis, the EPA/AA (odds ratio 0.18, 95%
      confidence interval 0.04-0.81, p=0.026) and DHA/AA (odds ratio 0.09, 95%
      confidence interval 0.02-0.33, p<0.001) ratios were inversely related to patients
      aged <65 years. According to age-stratified analyses, we found an association of
      aortic arch calcification with a lower EPA/AA ratio for patients aged >= 75 years
      and an association of multiple infarctions and cerebral white matter lesions with
      a lower EPA/AA ratio for patients aged 65-74 years (p<0.05). CONCLUSIONS: The
      ratios of EPA/AA and DHA/AA could be specific markers for younger stroke
      patients. The EPA/AA ratio may be related to aortic arch calcification for
      elderly stroke patients and to multiple infarctions and cerebral white matter
      disease for middle-aged stroke patients.

PMID- 29199201
TI  - Effects of a Dipeptidyl Peptidase 4 Inhibitor Sitagliptin on Glycemic Control and
      Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus (GLORIA Trial).
AB  - AIM: The morbidity of cardiovascular disease in patients with type 2 diabetes
      mellitus (DM) deteriorates in combination with dyslipidemia. The accumulation of
      remnant lipoproteins in patients with fasting and postprandial
      hypertriglyceridemia is highly atherogenic. The current study investigated
      whether the dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates dyslipidemia
      and hyperglycemia. METHODS: We enrolled 38 patients with type 2 DM (20 males and
      18 females, 65.7+/-9.9 years old, HbA1c levels <8.4%), and all patients gave
      written informed consent. Sitagliptin (50 mg/day) was added to current
      antidiabetic treatments and increased to 100 mg/day to achieve low HbA1c levels
      (<7.4%). Glucose and lipoprotein metabolism profiles were analyzed at 0, 4, and
      12 weeks after sitagliptin administration. RESULTS: Sitagliptin significantly
      decreased fasting levels of triglyceride (TG) (161+/-90 vs. 130+/-66 mg/dl,
      p<0.01) and non-HDL-C (129+/-29 vs. 116+/-20 mg/dl, p<0.01) in combination with
      glucose (150+/-47 vs. 129+/-27 mg/dl, p<0.01) and HbA1c (7.1+/-0.6 vs. 6.6+/-0.7
      mg/dl, p<0.001). Sitagliptin also significantly decreased the fasting levels of
      apolipoprotein (apo) B-48 (7.8+/-6.7 vs. 5.6+/-4.0 ug/ml, p<0.01), remnant
      lipoprotein cholesterol (15.3+/-9.5 vs. 12.0+/-7.9 mg/dl, p<0.05) and other
      apolipoproteins, such as apoB, apoC-II, apoC-III, and apoE. Analyses of the
      lipoprotein profiles of fasting sera revealed that sitagliptin significantly
      decreased cholesterol and TG levels of lipoprotein fractions in the size of very
      low density lipoprotein and low density lipoprotein. CONCLUSIONS: These findings
      indicated that sitagliptin administration ameliorated the lipid and lipoprotein
      profiles in patients with diabetes, which may be due to the decrease in
      atherogenic remnant lipoproteins (UMIN#000013218).

PMID- 29199202
TI  - The Influence of the Japanese Nationwide Cardiovascular Prevention System Health
      Guidance on Smoking Cessation Among Smokers: A Propensity Score Matching
      Analysis.
AB  - AIM: We investigated whether 2 types of personalized health guidance (repeated
      and single counseling) in the Japanese nationwide cardiovascular prevention
      system promoted smoking cessation among smokers. METHODS: The study included
      47,745 Japanese smokers aged 40 to 74 years classified into 2 personalized health
      guidance schemes. After a 1-year follow-up, we compared the rates of smoking
      cessation between individuals who had received counseling ("supported") and those
      who had not received counseling ("unsupported"). Using propensity score matching
      analysis, we estimated the average treatment effect (ATE) of each approach on
      smoking cessation after balancing out the characteristics between the supported
      and unsupported groups. The propensity score regression model included age,
      medical insurance type, weight gain since the age of 20 years, exercise, eating
      habits, alcohol intake, quality of sleep, readiness to modify lifestyle,
      willingness to receive support, and body mass index. RESULTS: In the repeated
      counseling scheme, the age-adjusted rates of smoking cessation in the supported
      and unsupported groups were 8.8% and 6.3% for males, and 9.8% and 9.1% for
      females respectively. In the single counseling scheme, the corresponding rates
      were 8.4% and 7.3% for supported and unsupported males, and 11.0% and 11.7% for
      supported and unsupported females respectively. The ATE of repeated counseling
      was +2.64% (95% confidence interval: +1.51% to +3.77%) for males and +3.11% (
      1.85% to +8.07%) for females. The ATE of single counseling was +0.61% (-1.17% to
      +2.38%) for males and -1.06% (-5.96% to +3.85%) for females. CONCLUSIONS: In the
      Japanese cardiovascular prevention system, repeated counseling may promote
      smoking cessation among male smokers.

PMID- 29199203
TI  - Hemophagocytic Syndrome Complicated with Dermatomyositis Controlled Successfully
      with Infliximab and Conventional Therapies.
AB  - A 57-year-old woman was admitted to our hospital because of a high fever, anemia,
      and hyperferritinemia. Since a bone marrow examination revealed hemophagocytosis,
      she was diagnosed with hemophagocytic syndrome (HPS). During treatment of HPS, a
      heliotrope rash and Gottron's sign appeared with elevated levels of serum
      aldolase. She also developed heart failure. She was diagnosed with
      dermatomyositis (DM) and associated myocarditis. Although the administration of
      glucocorticoids, calcineurin inhibitors, intravenous immunoglobulins, and
      etoposide ameliorated the clinical findings of DM and cytopenia, the fever and
      hyperferritinemia remained. The addition of infliximab to glucocorticoids and
      tacrolimus improved the fever and hyperferritinemia and enabled a reduction in
      the dose of prednisolone without relapse of the diseases.

PMID- 29199204
TI  - Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and
      lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1
      gene.
AB  - Segmental progeroid syndromes with lipodystrophy are extremely rare,
      heterogeneous, and complex multi-system disorders that are characterized by
      phenotypic features of premature aging affecting various tissues and organs. In
      this study, we present a "sporadic/isolated" Japanese woman who was ultimately
      diagnosed with mandibular hypoplasia, deafness, progeroid features, and
      progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome
      sequencing analysis. She had been suspected as having atypical Werner syndrome
      and/or progeroid syndrome based on observations spanning a 30-year period;
      however, repeated genetic testing by Sanger sequencing did not identify any
      causative mutation related to various subtypes of congenital partial
      lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD).
      Recently, MDPL syndrome has been described as a new entity showing progressive
      lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on
      chromosome 19 have been identified in patients with MDPL syndrome. To date, 21
      cases with POLD1-related MDPL syndrome have been reported worldwide, albeit
      almost entirely of European origin. Here, we identified a de novo mutation in
      exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome
      sequencing. To the best of our knowledge, this is the first identified case of
      MDPL syndrome in Japan. Our results provide further evidence that mutations in
      POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant
      across different ethnicities.

PMID- 29199205
TI  - Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular
      tumour of the thyroid: semi-automated techniques with manual antigen retrieval
      are more accurate than fully automated techniques.
AB  - Hyalinizing trabecular tumour (HTT) immunohistochemically shows cell membranous
      immunoreactivity for MIB-1. This aberrant immunoreactivity is an important factor
      for the diagnosis of HTT. However, fully automated stainers frequently fail to
      confirm the immunoreactivity. The aim of this study is to investigate the cause
      of false negative cell membranous immunoreactivity for MIB-1 in HTT using fully
      automated stainers, to determine potential reasons for the problem, and to
      establish methods confirming cell membranous immunoreactivity for MIB-1 in HTT.
      Six participating institutions examined immunoreactivity for MIB-1 in 10 HTT
      cases using two approaches: fully automated and semi-automated methods. In the
      latter, antigen retrieval was carried out using manual methods adopted for
      routine assays at each institute. The autostainers used included the BOND-MAX,
      BOND-III, Benchmark XT, and Omnis systems. Using fully automated methods,
      institute E showed cell membranous MIB-1 positivity in all HTT cases. In
      contrast, at institute D, all HTT cases were negative. The positive rates of the
      remaining four institutes ranged from 10% to 20%. The incidence of positive cases
      using semi-automated methods was 100%, 90%, 90%, 30%, 80%, and 100% at institutes
      A, B, C, D, E, and F, respectively. We assert that antigen retrieval should be
      conducted manually for diagnosis of HTT; furthermore, definitively diagnosed HTT
      should be prepared as the external positive control.

PMID- 29199206
TI  - Preparation of Salicylic Acid Loaded Nanostructured Lipid Carriers Using Box
      Behnken Design: Optimization, Characterization and Physicochemical Stability.
AB  - Nanostructured lipid carriers loaded salicylic acid (NLCs-SA) were developed and
      optimized by using the design of experiment (DOE). Box-Behnken experimental
      design of 3-factor, 3-level was applied for optimization of nanostructured lipid
      carriers prepared by emulsification method. The independent variables were total
      lipid concentration (X1), stearic acid to Lexol(r) GT-865 ratio (X2) and Tween(r)
      80 concentration (X3) while the particle size was a dependent variable (Y). Box
      Behnken design could create 15 runs by setting response optimizer as minimum
      particle size. The optimized formulation consists of 10% of total lipid, a
      mixture of stearic acid and capric/caprylic triglyceride at a 4:1 ratio, and 25%
      of Tween(r) 80 which the formulation was applied in order to prepare in both
      loaded and unloaded salicylic acid. After preparation for 24 hours, the particle
      size of loaded and unloaded salicylic acid was 189.62+/-1.82 nm and 369.00+/-3.37
      nm, respectively. Response surface analysis revealed that the amount of total
      lipid is a main factor which could affect the particle size of lipid carriers. In
      addition, the stability studies showed a significant change in particle size by
      time. Compared to unloaded nanoparticles, the addition of salicylic acid into the
      particles resulted in physically stable dispersion. After 30 days, sedimentation
      of unloaded lipid carriers was clearly observed. Absolute values of zeta
      potential of both systems were in the range of 3 to 18 mV since non-ionic
      surfactant, Tween(r) 80, providing steric barrier was used. Differential
      thermograms indicated a shift of endothermic peak from 55 degrees C for alpha
      crystal form in freshly prepared samples to 60 degrees C for beta'-crystal form
      in storage samples. It was found that the presence of capric/caprylic
      triglyceride oil could enhance encapsulation efficiency up to 80% and facilitate
      stability of the particles.

PMID- 29199207
TI  - Effects of Plant Sphingolipids on Inflammatory Stress in Differentiated Caco-2
      Cells.
AB  - To determine the mechanism underlying the anti-inflammatory effects of plant
      sphingolipids, especially plant glucosylceramide (GlcCer), the effects of plant
      sphingolipids on inflammatory stress in differentiated Caco-2 cells were compared
      to those of a sphingolipid of animal origin, galactosylceramide (GalCer).
      Addition of GlcCer or GalCer suppressed cell injury caused lipopolysaccharide
      (LPS)- and TNF-alpha-induced inflammatory stress and induction of apoptosis in
      differentiated Caco-2 cells. There was no difference in the suppressive effect
      between GlcCer and GalCer. The inflammatory cytokines and chemokines induced by
      LPS were suppressed by GlcCer. GlcCer remained on the cell surface. The results
      of this study can be summarized as follows: 1) sphingolipids such as GlcCer have
      potent anti-inflammatory effects; 2) GlcCer suppresses LPS-induced production of
      cytokines and apoptosis; 3) sphingolipids may remain on the surface of cells, and
      4) the chemical properties of sphingolipids may prevent the interaction between
      LPS and its receptor.

PMID- 29199208
TI  - Spontaneous Preparation of Highly Stable Gold Nanoparticle Stabilized with omega
      Sulfonylated Alkylsulfanylaniline.
AB  - Preparation, characterization, and stability evaluation of gold nanoparticles
      stabilized by omega-sulfonylated alkylsulfanylaniline have been described. The
      particle solution was obtained by the spontaneous reaction of HAuCl4 and omega
      sulfonylated alkylsulfanylaniline in boiling water. It showed a deep red color,
      owing to surface plasmon resonance of the resulting gold nanoparticles. The size
      and shape of the nanoparticles were pH-dependent, and pH 8 was found to be the
      most suitable condition to prepare stable nanoparticles with an average size of
      11.2 +/- 5.9 nm. The resulting particle solution was stable for a wide range of
      pH (3-13) and in phosphate-buffered saline (PBS) solution. The nanoparticles were
      storable as dried powder for at least two weeks, and were redispersible in water
      or PBS to give almost the same absorption spectra as the freshly prepared
      solution. Nanoparticle modification was achieved by simply adding thiol molecules
      to the particle solution.

PMID- 29199209
TI  - Effect of HCl Loading and Ethanol Concentration over HCl-Activated Clay Catalysts
      for Ethanol Dehydration to Ethylene.
AB  - Montmorillonite clay (MMT) is one of materials that can be "green material" due
      to its environmental safety. In this work, acid-activated MMT catalysts were
      prepared for the dehydration reaction of ethanol. To be the green process, the
      reaction with bioethanol was also studied. Ethanol concentrations in feed were
      varied in the range of 10-99.95 wt%. Moreover, the concentrations of hydrochloric
      acid activated MMT were investigated in range of 0.05-4 M. From the experiment,
      it reveals that different acid concentrations to activate MMT affect the
      catalytic activity of catalysts. The 0.3 M of HCl activated MMT exhibits the
      highest activity (under the best condition of 30 ml HCl aging for 1 h) with the
      Si/Al ratio of 7.4. It can reach the ethanol conversion and ethylene selectivity
      up to 95% and 98% at reaction temperature of 400 degrees C, respectively. For the
      several ethanol feed concentrations, it does not remarkably affect in ethanol
      conversion. However, it has some different effect on ethylene selectivity between
      lower and higher reaction temperatures. It was found that at lower temperature
      reaction, ethylene selectivity is high due to the behavior of water in feed. In
      addition, the 0.3 M-MMT can be carried out under the hydrothermal effect.

PMID- 29199210
TI  - X-band Electron Paramagnetic Resonance Investigation of Stable Organic Radicals
      Present under Cold Stratification in 'Fuji' Apple Seeds.
AB  - We investigated stable organic radicals formed in response to cold stratification
      in 'Fuji' apple seeds using X-band (9 GHz) electron paramagnetic resonance (EPR)
      technique. This technique primarily detected two paramagnetic species in each
      seed. These two different radical species were assigned as a stable organic
      radical and Mn2+ species based on the g values and hyperfine components. Signal
      from the stable radicals was noted at a g value of about 2.00 and was strong and
      relatively stable. Significant radical intensity changes were observed in apple
      seeds on refrigeration along with water supplementation. The strongest radical
      intensity and a very weak Mn2+ signal were also observed for the seeds kept in
      moisture-containing sand in a refrigerator. Noninvasive EPR of the radicals
      present in each seed revealed that the stable radicals were located primarily in
      the seed coat. These results indicate that the significant radical intensity
      changes in apple seeds under refrigeration for at least 90 days followed by water
      supplementation for one week, can be related to cold stratification of the seeds.

PMID- 29199211
TI  - Membrane vesicle protein PagC as a novel biomarker for detecting pathogenic
      Salmonella in the viable but not culturable state.
AB  - The viable but non-culturable (VBNC) state is a remarkable survival mechanism in
      which cells exist in a physiologically inactive state. Bacteria in the VBNC state
      do not form colonies, and thus, are difficult to detect using colony-based
      methods. As a result, VBNC bacteria are potentially virulent and can cause
      widespread contamination during food production. In the present study, we
      reported a novel biomarker, the membrane vesicle protein PagC, for the detection
      of VBNC Salmonella. Salmonella cells were chemically induced into the VBNC state
      by H2O2 treatment. The bacterial cells retained their shapes but were observed to
      release numerous membrane vesicles, which were accompanied by a transient PagC
      overexpression. Immunoblotting was performed to detect PagC in pathogenic
      strains, including Salmonella Enteritidis and S. Typhimurium, which are harmful
      and known to cause food-borne gastroenteritis in humans and other animals.
      Therefore, our findings demonstrated the potential use of PagC as a biomarker for
      the detection of VBNC Salmonella in food production.

PMID- 29199212
TI  - Branching patterns of the aortic arch in the Siberian roe deer (Capreolus
      pygargus Pallas, 1771).
AB  - This study examined the branching pattern of the aortic arch (AA) and its major
      branches in the Siberian roe deer (Capreolus pygargus Pallas, 1771) from South
      Korea. A total of eight of the nine expected types, based on the branching site
      and bilateral levels of the costocervical trunk (CCT) and subclavian artery (SB),
      were observed in the arterial silicone casts of 35 deer (16 males, 19 females).
      This deer has no typical type. The three most common types were present in 28.6,
      25.7 and 20.0% of cases and resulted from different branching patterns of the
      left CCT and left SB. These results suggest that the Siberian roe deer in the
      Korean peninsula has various AA branching patterns, which differs from other
      ruminants.

PMID- 29199213
TI  - Variation of amino acid sequences of serum amyloid a (SAA) and
      immunohistochemical analysis of amyloid a (AA) in Japanese domestic cats.
AB  - Amyloid A (AA) amyloidosis, a fatal systemic amyloid disease, occurs secondary to
      chronic inflammatory conditions in humans. Although persistently elevated serum
      amyloid A (SAA) levels are required for its pathogenesis, not all individuals
      with chronic inflammation necessarily develop AA amyloidosis. Furthermore, many
      diseases in cats are associated with the elevated production of SAA, whereas only
      a small number actually develop AA amyloidosis. We hypothesized that a genetic
      mutation in the SAA gene may strongly contribute to the pathogenesis of feline AA
      amyloidosis. In the present study, genomic DNA from four Japanese domestic cats
      (JDCs) with AA amyloidosis and from five without amyloidosis was analyzed using
      polymerase chain reaction (PCR) amplification and direct sequencing. We
      identified the novel variation combination of 45R-51A in the deduced amino acid
      sequences of four JDCs with amyloidosis and five without. However, there was no
      relationship between amino acid variations and the distribution of AA amyloid
      deposits, indicating that differences in SAA sequences do not contribute to the
      pathogenesis of AA amyloidosis. Immunohistochemical analysis using antisera
      against the three different parts of the feline SAA protein-i.e., the N-terminal,
      central, and C-terminal regions-revealed that feline AA contained the C-terminus,
      unlike human AA. These results indicate that the cleavage and degradation of the
      C-terminus are not essential for amyloid fibril formation in JDCs.

PMID- 29199214
TI  - Expression of Two RpoH Sigma Factors in Sinorhizobium meliloti upon Heat Shock.
AB  - The plant symbiotic alpha-proteobacterium Sinorhizobium meliloti has two RpoH
      type sigma factors, RpoH1 and RpoH2. The former induces the synthesis of heat
      shock proteins and optimizes interactions with the host. Using a Western blot
      analysis, we examined time course changes in the intracellular contents of these
      factors upon a temperature upshift. The RpoH1 level was relatively high and
      constant, suggesting that its regulatory role in the heat shock response is
      attained through the activation of the pre-existing RpoH1 protein. In contrast,
      the RpoH2 level was initially undetectable, and gradually increased. These
      differential patterns reflect the functional diversification of these factors.

PMID- 29199216
TI  - Development of Highly Sensitive Analytical Methods for Biologically Relevant
      Materials and Their Pharmaceutical Applications.
AB  - One important aspect of analytical chemistry research in the pharmaceutical
      sciences is the development of diagnostic and therapeutic analyses for disease,
      and the development of analytical methods for elucidating the causes of disease.
      I have been focusing on developing a highly sensitive method for measuring trace
      amounts of specific components in biological samples. This research can be
      roughly divided into three approaches: the use of immunoassays and DNA
      hybridization as methods utilizing specific affinities, the use of capillary
      electrophoresis as a highly sensitive and rapid separation method, and the use of
      chemiluminescence and bioluminescence reactions. The components being measured
      are compounds such as hormones, tumor markers, drugs, reactive oxygen species and
      genes in biological samples for the purpose of developing therapies for the
      prevention and treatment of diseases.

PMID- 29199215
TI  - Isotopic Fractionation of Sulfur in Carbonyl Sulfide by Carbonyl Sulfide
      Hydrolase of Thiobacillus thioparus THI115.
AB  - Carbonyl sulfide (COS) is one of the major sources of stratospheric sulfate
      aerosols, which affect the global radiation balance and ozone depletion. COS
      degrading microorganisms are ubiquitous in soil and important for the global flux
      of COS. We examined the sulfur isotopic fractionation during the enzymatic
      degradation of COS by carbonyl sulfide hydrolase (COSase) from Thiobacillus
      thioparus THI115. The isotopic fractionation constant (34E value) was -2.2+/
      0.20/00. Under experimental conditions performed at parts per million by volume
      level of COS, the 34E value for intact cells of T. thioparus THI115 was -3.6+/
      0.70/00, suggesting that, based on Rees' model, the 34E value mainly depended on
      COS transport into the cytoplasm. The 34E value for intact cells of T. thioparus
      THI115 was similar to those for Mycobacterium spp. and Williamsia sp., which are
      known to involve the conserved region of nucleotide sequences encoding the clade
      D of beta-class carbonic anhydrase (beta-CA) including COSase. On the other hand,
      the 34E value was distinct from those for bacteria in the genus Cupriavidus.
      These results provide an insight into biological COS degradation, which is
      indispensable for estimating the COS global budget based on the isotope because
      of the significant contribution of COS degradation by microorganisms harboring
      beta-CA family enzymes.

PMID- 29199217
TI  - A Novel Probe with a Chlorinated alpha-Cyanoacetophenone Acceptor Moiety Shows
      Near-Infrared Fluorescence Specific for Tau Fibrils.
AB  - Development of a novel, tau-selective near-infrared fluorescence (NIRF) probe was
      attempted by combining the 3,5-dimethoxy-N,N-dimethylaniline-4-yl moiety with an
      alpha-cyanoacetophenone via hexatrienyl pi-linker. In particular, for structure
      activity relationship study of the alpha-cyanoacetophenones, a chlorine
      substituent was introduced to the aromatic ring to give a series of compounds (2a
      2d). Among those, compound 2c with meta-chloro aryl substituent was identified as
      a tau-selective NIRF probe: selectivity for tau over amyloid beta (Abeta) and
      bovine serum albumin (BSA) was estimated to be 10.3 and 19.5 fold, respectively.
      The mechanism for tau-selectivity of 2c was found to be based on the specific
      recognition of the microenviroment of tau fibrils, which was endowed by its
      molecular rotor-like properties. The tau-selective NIRF probe 2c was also able to
      stain tau fibrils in tau-green fluorescent protein (GFP)-transgenic human
      neuroblastoma cells (SH-SY5Y cells).

PMID- 29199218
TI  - Uses of Cyclohexan-1,4-dione for the Synthesis of 2-Amino-4,5
      dihydrobenzo[b]thiophen-6(7H)-one Derivatives with Anti-proliferative and Pim-1
      Kinase Activities.
AB  - The reaction of cyclohexan-1,4-dione with elemental sulfur and any of the 2-cyano
      N-arylacetamide derivatives 2a-c gave the 2-amino-4,5-dihydrobenzo[b]thiophen
      6(7H)-one derivatives 3a-c to be used in some heterocyclization reactions. The
      multicomponent reactions of any of compounds 3a-c with aromatic aldehydes 6a-c
      and either of malononitrile or ethylcyanoacetate gave the 5,9-dihydro-4H
      thieno[2,3-f]chromene derivatives 9a-r, respectively. The anti-proliferative
      evaluation of the newly synthesized compounds against the six cancer cell lines
      A549, HT-29, MKN-45, U87MG, SMMC-7721 and H460 showed that the nine compounds 3c,
      5c, 9e, 9h, 9i, 9j, 9l, 9q, 11e and 13e with highest cytotoxcity. Toxicity of
      these compounds against shrimp larvae revealed that compounds 3c, 9j, 9q, and 13e
      showed no toxicity against the tested organisms. The c-Met kinase inhibition of
      the most potent compounds showed that compounds 9j, 9q, 10e, 12e and 13e have the
      highest activities. Compounds 9j, 9l, 9q and 11e showed high activity towards
      tyrosine kinases. Moreover, compounds 9j, 9q and 13e showed the highest inhibitor
      activity towards Pim-1 kinase.

PMID- 29199219
TI  - Novel Non-carboxylate Benzoylsulfonamide-Based Protein Tyrosine Phosphatase 1B
      Inhibitors with Non-competitive Actions.
AB  - A novel series of benzoylsulfonamide derivatives were synthesized and
      biologically evaluated. Among them, 4-(biphenyl-4-ylmethylsulfanylmethyl)-N
      (hexane-1-sulfonyl)benzamide (compound 18K) was identified as a protein tyrosine
      phosphatase 1B (PTP1B) inhibitor with potent and selective inhibitory activity
      against PTP1B (IC50=0.25 uM). Compound 18K functioned as a non-competitive
      inhibitor and bound to the allosteric site of PTP1B. It also showed high oral
      absorption in mice (the maximum drug concentration (Cmax)=45.5 uM at 30 mg/kg),
      rats (Cmax=53.6 uM at 30 mg/kg), and beagles (Cmax=37.8 uM at 10 mg/kg), and
      significantly reduced plasma glucose levels at 30 mg/kg/d (per os (p.o.)) for one
      week with no side effects in db/db mice. In conclusion, the substituted
      benzoylsulfonamide was shown to be a novel scaffold of a non-competitive and
      allosteric PTP1B inhibitor, and compound 18K has potential as an efficacious and
      safe anti-diabetic drug as well as a useful tool for investigations of the
      physiological and pathophysiological effects of allosteric PTP1B inhibition.

PMID- 29199220
TI  - Chemical Synthetic Platform for Chlorpromazine Oligomers That Were Reported as
      Photo-degradation Products of Chlorpromazine.
AB  - A synthetic platform for chlorpromazine (CPZ) oligomers, which could be generated
      via photo-reaction of CPZ, is essential to promote their biological and
      structural studies. In this paper, the first synthetic platform for CPZ oligomers
      is described. A photo-irradiation experiment of CPZ to confirm whether the
      structure of the CPZ dimer generated by the photo-irradiation was identical to
      that prepared by our synthetic method is also reported.

PMID- 29199221
TI  - Synthesis of Tetrahydrobiphenylene via Pd(0)-Catalyzed C(sp2)-H
      Functionalization.
AB  - Tetrahydrobiphenylene consists of cyclobutene fused with benzene and cyclohexene
      rings. In this paper, a direct method for synthesizing tetrahydrobiphenylenes
      based on a palladium (Pd)(0)-catalyzed C(sp2)-H functionalization was
      investigated. The developed method was applied to the synthesis of several
      tetrahydrobiphenylenes having an oxygen functionality at the ring juncture. The
      derivatization of a tetrahydrobiphenylene is also reported.

PMID- 29199222
TI  - Differences in Powder Properties of Two 1,4-Dihydropyridine-Type Compounds
      Evaluated through Thermal Analysis.
AB  - The powder properties of two 1,4-dihydropyridine type compounds, manidipine
      dihydrochloride (Man) and benidipine hydrochloride (Ben), which possess similar
      physicochemical properties, were compared through thermal and mechanical
      analyses. Man and Ben were compressed with lactose monohydrate (Lac) and
      magnesium stearate (Mgst) at different compression forces. As an index, we
      focused on the onset temperatures of Lac dehydration during thermal analysis and
      plotted them against compression forces to evaluate the differences in powder
      properties between Man and Ben. To discuss in detail, the Lac ratio was selected
      as a formulation factor and compression speed as a process factor, which would be
      influenced to the onset temperature or its profile. It could be represented that
      Man was more adherent than Ben through thermal analysis by changing these
      critical factors, which were consistent with the results obtained through
      mechanical analysis.

PMID- 29199223
TI  - Asymmetric Conjugate Additions of Carbonyl Compounds to Nitroalkenes under
      Solvent-Free Conditions Using Fluorous Diaminomethylenemalononitrile
      Organocatalyst.
AB  - The novel fluorous organocatalyst bearing a diaminomethylenemalononitrile motif
      is prepared. The fluorous organocatalyst efficiently promotes asymmetric
      conjugate additions of ketones to nitroalkenes and results in high yields of
      these addition products with excellent enantioselectivities under solvent-free
      conditions.

PMID- 29199224
TI  - p-Coumaroyl Malate Derivatives of the Pandanus amaryllifolius Leaf and Their
      Isomerization.
AB  - A novel p-coumaroyl dimethyl malate (1) was isolated from the Pandanus
      amaryllifolius leaf in addition to three known analogs of p-coumaroyl dimethyl
      malate (2-4), and their structures were elucidated by analysis of the
      spectroscopic data. The p-coumaroyl malate derivatives were isolated as a mixture
      of E and Z isomers. To determine the cause of isomerization, the p-coumaroyl
      malate isolated in this study was synthesized. We concluded that the Z isomer
      might be an artifact generated from the E isomer through purification steps.

PMID- 29199225
TI  - Flavonoid Glycosides from Sedum bulbiferum.
AB  - The MeOH extract from dried whole Sedum bulbiferum MAKINO (Crassulaceae) plants
      yielded 34 compounds, including six new flavonoid glycosides and 28 known
      compounds. The structures of new compounds were established using NMR, Mass
      spectroscopic analysis and chemical evidence.

PMID- 29199226
TI  - Imaging of Sialidase Activity and Its Clinical Application.
AB  - Sialidase releases sialic acid residues from the ends of sugar chains. The
      sialidases are involved in many physiological processes including cell
      differentiation and proliferation and immune function as well as
      pathophysiological conditions such as various human cancers and infections.
      Therefore visualization of sialidase activities with high sensitivity could
      provide valuable insights into these isozyme's activity. We developed novel
      fluorescent sialidase substrates, 2-benzothiazol-2-yl-phenol derivatives-based N
      acetylneuraminic acid (Neu5Ac) (BTP-Neu5Ac) substrates, for highly sensitive and
      specific visualization of sialidase activity in living mammalian tissues and
      virus-infected cells. We found that BTP-Neu5Ac can visualize sialidase activities
      sensitively and selectively in rat tissues including brain slices. BTP-Neu5Ac can
      also clearly detect cancer cells implanted orthotopically in mouse colons and
      human colon cancers. In this review, I describe imaging of sialidase activity
      with BTP-Neu5Ac in animal tissues, detection of colon cancer, memory formation,
      detection of virus-infected cells, and application to drug-resistant influenza
      virus detection and separation.

PMID- 29199228
TI  - Progression of Time-Dependent Changes to the Mechanisms of Vasodilation by
      Protease-Activated Receptor 2 in Metabolic Syndrome.
AB  - Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by
      serine proteases released from tissues or by synthetic peptide ligands
      administered pharmacologically. Its wide expression in the cardiovascular system,
      particularly within the endothelium, vasodilation activity, and link to increased
      expression of inflammatory cytokines positions PAR2 as a potentially important
      regulator of vascular pathology under conditions of tissue inflammation, and
      injury; and thus, a pharmaceutical target for new therapeutics. Obesity is
      considered a chronic low-grade systemic inflammatory condition as inflammatory
      cytokines released from adipocytes are closely related to development of
      metabolic syndrome and related disorders. Our work over the past five-years has
      focused on the changes in vasomotor functions of PAR2 in metabolic syndrome,
      using an animal model known as the SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP.ZF). In
      young SHRSP.ZF that had already developed impaired responses to nitric oxide, we
      reported that PAR2-induced endothelium-dependent vasodilation is preserved.
      However, this PAR2 vasodilation decreased with increasing age and further chronic
      exposure to the conditions of metabolism disorder. These findings raise the
      possibility that PAR2 regulates tissue perfusion and can protect organs from
      injury, which is an increasing clinical concern at later stages of metabolic
      syndrome. Here we present our studies on the time-dependent changes in
      vasoreactivity to PAR2 in metabolic syndrome and the underlying mechanisms.
      Furthermore, we discuss the implications of these age-related changes in PAR2 for
      the cardiovascular system in metabolic syndrome.

PMID- 29199229
TI  - Mammalian Target of Rapamycin (mTOR) as a Potential Therapeutic Target in
      Pathological Ocular Angiogenesis.
AB  - Pathological ocular angiogenesis is a causative factor of retinopathy of
      prematurity, proliferative diabetic retinopathy, and wet age-related macular
      degeneration. Vascular endothelial growth factor (VEGF) plays an important role
      in pathological angiogenesis, and anti-VEGF agents have been used to treat the
      ocular diseases that are driven by pathological angiogenesis. However, adverse
      effects associated with the blockade of VEGF signaling, including impairments of
      normal retinal vascular growth and retinal function, were suggested. Therefore,
      the development of a safe, effective strategy to prevent pathological ocular
      angiogenesis is needed. Recent studies have demonstrated that inhibitors of the
      mammalian target of rapamycin (mTOR) target proliferating endothelial cells
      within the retinal vasculature. Here, we review the potential of targeting the
      mTOR pathway to treat pathological ocular angiogenesis.

PMID- 29199230
TI  - New Insights into the Role of Basement Membrane-Derived Matricryptins in the
      Heart.
AB  - The extracellular matrix (ECM), which contributes to structural homeostasis as
      well as to the regulation of cellular function, is enzymatically cleaved by
      proteases, such as matrix metalloproteinases and cathepsins, in the normal and
      diseased heart. During the past two decades, matricryptins have been defined as
      fragments of ECM with a biologically active cryptic site, namely the
      'matricryptic site,' and their biological activities have been initially
      identified and clarified, including anti-angiogenic and anti-tumor effects. Thus,
      matricryptins are expected to be novel anti-tumor drugs, and thus widely
      investigated. Although there are a smaller number of studies on the expression
      and function of matricryptins in fields other than cancer research, some
      matricryptins have been recently clarified to have biological functions beyond an
      anti-angiogenic effect in heart. This review particularly focuses on the
      expression and function of basement membrane-derived matricryptins, including
      arresten, canstatin, tumstatin, endostatin and endorepellin, during cardiac
      diseases leading to heart failure such as cardiac hypertrophy and myocardial
      infarction.

PMID- 29199231
TI  - Augmented Contractility to Noradrenaline in Femoral Arteries from the Otsuka Long
      Evans Tokushima Fatty Rat, a Model of Type 2 Diabetes.
AB  - Although vasculopathies may occur systemically, there are few reports regarding
      femoral arteries of type 2 diabetes. Here, we investigated whether contractile
      response to noradrenaline in femoral arteries would change in type 2 diabetic
      male Otsuka Long-Evans Tokushima Fatty (OLETF) rat at the chronic stage of
      disease (1 year old) versus age-matched control Long-Evans Tokushima Otsuka
      (LETO) rat. OLETF rat exhibited hyperglycemia, hypertension, hyperlipidemia, and
      hypoinsulinemia compared to age-matched LETO rat. Noradrenaline-induced
      contraction was increased in femoral arteries in OLETF rats compared with LETO
      rats whereas serotonin- or phenylephrine-induced contractions were similar
      between these two animals. Acetylcholine- and sodium nitroprusside-induced
      relaxations were similar between the two groups. Very small relaxations in
      femoral arteries induced by clonidine and isoprenaline were obtained in LETO but
      not OLETF group. Noradrenaline-induced contraction was enhanced by treatment with
      NG-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, and the
      between-group difference of contraction was eliminated by such treatment.
      Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, reduced
      noradrenaline-induced contraction in both groups, whereas the contraction was
      greater in OLETF group versus LETO. Femoral arterial protein expression of
      endothelial NOS, COX-1, and superoxide dismutases were similar between the two
      groups, whereas reduction of COX-2 expression was seen in OLETF group compared
      with LETO. Increased contractile responsiveness to noradrenaline is seen in OLETF
      rat femoral artery and this may be due to reduction of suppressive effect of NO.

PMID- 29199232
TI  - Supplemented Chondroitin Sulfate and Hyaluronic Acid Suppress Mineralization of
      the Chondrogenic Cell Line, ATDC5, via Direct Inhibition of Alkaline Phosphatase.
AB  - Chondroitin sulfate (CS) is a sulfated polysaccharide produced by chondrocytes.
      Alkaline phosphatase (ALP) is an important enzyme involved in the mineralization
      of chondrocytes. In recent years, it has been reported that CS regulates the
      differentiation of various cells. In this study, we investigated the effect of
      supplemented CS on ALP activity and mineralization of the chondrogenic cell line,
      ATDC5. In addition, hyaluronic acid (HA), a non-sulfated and acidic
      polysaccharide, was used in comparison to CS. CS and HA significantly suppressed
      ALP activity without affecting ATDC5 cell proliferation. In addition, although
      the inhibition of ALP activity was observed at every time point, Alp mRNA
      expression level was not affected by CS. The suppressive effect of CS on ALP
      activity was abrogated by pre-treatment with chondroitinase ABC (CSase). CS and L
      homoarginine (hArg), an inhibitor of ALP, significantly suppressed mineralization
      in ATDC5 cells. In conclusion, supplemented CS directly inhibits ALP to prevent
      the progression of chondrocytes from differentiation to mineralization.

PMID- 29199233
TI  - Inhibition of Laser-Induced Choroidal Neovascularization by Hematoporphyrin
      Dimethylether-Mediated Photodynamic Therapy in Rats.
AB  - This study aimed to investigate the effect of hematoporphyrin dimethylether
      (HDME)-mediated photodynamic therapy for laser-induced choroidal
      neovascularization (CNV) in adult Brown Norway rats. HDME was administered via
      tail vein at 14 d after the laser photocoagulation, and the rats received
      irradiance with a laser light at 570 nm at 15 min after injection. CNV was
      evaluated by fundus photography, fundus fluorescein angiography, optical
      coherence tomography, and hematoxylin and eosin staining. We found that CNV was
      occurred at 7 d after photocoagulation and reaching peak activity at 14 d after
      photocoagulation. There is a significant reduction in the total area of the
      fluorescein leakage and the number of strong fluorescein leakage spots on 7 d
      after HDME-mediated photodynamic therapy (PDT). The results suggest that HDME
      mediated PDT inhibits laser-induced CNV in rats, representing a promising therapy
      for wet age-related macular degeneration.

PMID- 29199234
TI  - The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer's Disease
      Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling.
AB  - Ziziphus jujuba is a plant, which bears fruits and seeds that are used for
      medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba
      var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in
      Chinese and Korean medicines. Recent findings have indicated that EZJ improves
      memory impairment, a common symptom of various neurological diseases. However,
      the effects of EZJ on amyloid beta (Abeta) toxicity, which is a main cause of
      Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential
      anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the
      effect of standardized EZJ on Abeta-induced synaptic long-term potentiation (LTP)
      deficit in the hippocampal tissue. EZJ blocked Abeta-induced LTP deficits in a
      concentration-dependent manner. Moreover, EZJ increased brain-derived
      neurotrophic factor (BDNF) level in naive hippocampal slices. The finding that
      the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ
      ameliorates the Abeta-induced LTP deficit through BDNF/topomyosin receptor kinase
      B (TrkB) signaling. However, transcription or translation inhibitors failed to
      block the effect of EZJ, suggesting that BDNF synthesis is not required for the
      action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In
      contrast, plasmin inhibitor blocked the effect of EZJ on the Abeta-induced LTP
      deficit. Our findings indicate that EZJ ameliorates Abeta-induced LTP deficits
      through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of
      EZJ on the post-translation modification of BDNF.

PMID- 29199235
TI  - Factors Influencing the Appearance of Oxaliplatin-Induced Allergy.
AB  - Several studies reported that the administration of oxaliplatin often induced
      allergy, but few studies have analyzed the pathogenesis. In this study, we
      examined the relationship between the incidence of allergy and status of
      oxaliplatin administration, patient background, laboratory data, or combined
      drugs. The subjects were 144 patients with colorectal or gastric cancer in whom
      oxaliplatin administration was started and completed between 2010 and 2016. They
      were divided into 2 groups: allergy and non-allergy groups. We extracted
      important factors influencing its appearance using multivariate analysis, and
      analyzed items of which the influence was suggested, using receiver operating
      characteristic (ROC) analysis. In 11 patients (7.6%), allergy appeared. The
      median frequency of appearance was 9 times (range: 5-13), being similar to that
      previously reported. On multivariate analysis, albumin (Alb) was extracted as an
      important factor. The cut-off value of Alb for the risk of allergy was 4.1 g/dL.
      An increase in the number of protein conjugates may have increased the risk of
      functioning as a hapten. Furthermore, the results suggested that the more
      frequency of oxaliplatin administration might increase the incidence of allergy,
      although it was not extracted as an important factor. In addition to young and
      female patients, as previously indicated, careful follow-up may be necessary for
      those with an Alb level of >=4.1 g/dL especially after the 6th course.

PMID- 29199236
TI  - Characterization of an L-Carnitine Transport System in Murine Photoreceptor Cell
      Line.
AB  - While it is well known that L-carnitine [3-hydroxy-4-(trimethylazaniumyl)
      butanoate] is an essential molecule for beta-oxidation, it provides anti
      oxidative effects as well. Since these effects have been observed in
      photoreceptor cells, the carnitine's intracellular concentration is considered to
      play a protective role against oxidative damage to those cells. However, even
      though its high hydrophilicity makes it likely that carnitine import is
      accomplished via a dedicated host transport system, the specific uptake process
      into those cells is currently unknown. Therefore, in this study, we sought to
      identify and characterize photoreceptor cell carnitine uptake transporter(s)
      utilizing 661W cells as a photoreceptor cell model. The results of our uptake
      assays showed that carnitine was transported into 661W cells in a saturable
      manner (Km=5.5 mM), and that the activity was susceptible to extracellular pH and
      Na+. While these data suggest the involvement of a transporter in 661W cell
      carnitine uptake, the observed transport profile did not correspond to any of the
      currently known carnitine transporters such as organic cation/carnitine
      transporter 1 (Octn1), Octn2, Octn3, B0,+ and Ct2. In fact, in our experiments,
      the mRNA expressions for such carnitine transporters in 661W cells were
      consistently very low and the carnitine transporter substrates did not inhibit
      the uptake activities. Taken as a whole, our results indicate that carnitine is
      transported into 661W cells in a carrier-mediated manner. However, since its
      transport modes cannot be fully explained by known carnitine transporters, it is
      highly likely that photoreceptor cells utilize a unique molecularly-based
      carnitine uptake system.

PMID- 29199237
TI  - Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5
      Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea
      Development.
AB  - 5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause
      severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif)
      ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were
      drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST)
      is prescribed in Japan for treat gastritis, stomatitis, and inflammatory
      diarrhea. We therefore examined the effects of HST and its active ingredients on
      5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the
      effects of HST on 5-FU-induced diarrhea development in the mouse. The distal
      colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5
      FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per
      os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of
      CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1
      mRNA in the colon but the effect by 5-FU was markedly suppressed by application
      of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa
      B (NF-kappaB) was activated by 5-FU treatment in cultured colon tissue, which was
      also suppressed by HST and the combination of baicalein and 6-gingerol.
      Furthermore, HST reduced 5-FU-induced diarrhea development. Under such
      experimental condition, CXCL1 gene, protein levels of neutrophil elastase and
      myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST.
      These findings suggest that HST, especially baicalein and 6-gingerol, prevent the
      development of neutrophil recruitment and diarrhea by the inhibition of NF-kappaB
      activity.

PMID- 29199238
TI  - SELEX-Based Screening of Exosome-Tropic RNA.
AB  - Cell-derived nanosized vesicles or exosomes are expected to become delivery
      carriers for functional RNAs, such as small interfering RNA (siRNA). A method to
      efficiently load functional RNAs into exosomes is required for the development of
      exosome-based delivery carriers of functional RNAs. However, there is no method
      to find exosome-tropic exogenous RNA sequences. In this study, we used a
      systematic evolution of ligands by exponential enrichment (SELEX) method to
      screen exosome-tropic RNAs that can be used to load functional RNAs into exosomes
      by conjugation. Pooled single stranded 80-base RNAs, each of which contains a
      randomized 40-base sequence, were transfected into B16-BL6 murine melanoma cells
      and exosomes were collected from the cells. RNAs extracted from the exosomes were
      subjected to next round of SELEX. Cloning and sequencing of RNAs in SELEX
      screened RNA pools showed that 29 of 56 clones had a typical RNA sequence. The
      sequence found by SELEX was enriched in exosomes after transfection to B16-BL6
      cells. The results show that the SELEX-based method can be used for screening of
      exosome-tropic RNAs.

PMID- 29199239
TI  - Evaluation of Drug-Induced Photosensitivity Using the Japanese Adverse Drug Event
      Report (JADER) Database.
AB  - Drug-induced photosensitivity (DIP) refers to the development of cutaneous
      disorders caused by the combined effects of different medications and light. The
      aim of this study was to obtain new information on drug risk comparisons and on
      DIP onset profiles, including seasonal variations, for clinically used
      prescription drugs. We analyzed reports of DIP recorded in the Japanese Adverse
      Drug Event Report (JADER) database using a reporting odds ratio (ROR). We also
      used Weibull proportional-hazards models for each drug to examine the patterns of
      DIP. The JADER database contains 430587 reports recorded from April 2004 to
      November 2016. The ROR values (95% confidence interval [CI]) of
      losartan/hydrochlorothiazide (HCTZ), valsartan/HCTZ, and ketoprofen were 214.5
      (162.1-283.9), 104.7 (66.3-165.5), and 117.9 (76.6-181.5), respectively. For time
      to-onset analysis, the median durations (interquartile range) for DIP caused by
      losartan/HCTZ, valsartan/HCTZ, and ketoprofen were 56 (41-78), 49 (38-88), and 8
      (2-14) days, respectively. The lower limit of the 95% CI for the Weibull shape
      parameter beta value for losartan/HCTZ was greater than 1. More than half of the
      reports of DIP onset following the administration of ketoprofen were recorded
      within 10 d of treatment initiation. The seasonal variation of photosensitivity
      reactions was shown to follow an annual sinusoidal pattern with a peak in April
      and May. Based on the results, losartan/HCTZ, valsartan/HCTZ, and ketoprofen
      should be used carefully in clinical practice to avoid DIP.

PMID- 29199240
TI  - Improvement of the Solubility and Intestinal Absorption of Curcumin by N-Acyl
      Taurates and Elucidation of the Absorption-Enhancing Mechanisms.
AB  - In this study, the effects of N-acyl taurates (NATs) on the intestinal absorption
      of curcumin (CUR), a water-insoluble and poorly absorbed compound, were examined
      in rats. Sodium methyl lauroyl taurate (LMT) and sodium methyl cocoyl taurate
      (CMT) were the most effective in increasing the solubility and intestinal
      absorption of CUR. The intestinal membrane toxicity of the NATs was also
      evaluated by measuring the activity of lactate dehydrogenase (LDH), a toxicity
      marker. NATs did not increase the activity of LDH, suggesting that they may be
      safely administered orally. We further elucidated the absorption-enhancing
      mechanisms of NATs by using Caco-2 cells. In cellular transport studies, LMT and
      CMT reduced the transepithelial electrical resistance value of Caco-2 cells and
      increased the transport of 5(6)-carboxyfluorescein and CUR. Hence, the intestinal
      absorption enhancement by LMT and CMT was attributed to the synergistic effect of
      higher solubility and greater permeability of the cell layer towards CUR in the
      presence of the surfactants. In summary, co-administration of CUR with either LMT
      or CMT is a simple and effective method to enhance oral delivery of CUR.

PMID- 29199241
TI  - Packaging of the Coenzyme Q10 into a Liposome for Mitochondrial Delivery and the
      Intracellular Observation in Patient Derived Mitochondrial Disease Cells.
AB  - While Coenzyme Q10 (CoQ10) is thought to be effective for the treatment of a
      variety of diseases, it limits its cellular uptake. Because of the hydrophobic
      nature of CoQ10, it is reasonable to assume that it could be encapsulated within
      a liposomal carrier. Several reports regarding the packaging of CoQ10 in
      liposomes have appeared, but detailed investigations of the preparation of CoQ10
      encapsulated liposomes have not been reported. As a result, information regarding
      the optimal method of packaging CoQ10 in liposomes is not available. In this
      study, several types of liposomes were prepared using different methods and their
      characteristics were compared. Since CoQ10 is mainly located in the inner
      mitochondrial membrane, a liposome that targets mitochondria, a MITO-Porter, was
      used as a model liposome. It was possible to incorporate high levels of CoQ10
      into the carrier. Transmission electron microscopy analyses showed that an empty
      MITO-Porter and the CoQ10-MITO-Porter were structurally different from one
      another. Even though significant structural differences were observed,
      mitochondrial delivery was not affected in mitochondrial disease fibroblast
      cells, as evidenced by confocal laser scanning microscopy observations. The
      results reported herein suggest that the CoQ10-MITO-Porter might be a suitable
      candidate for the potential medical therapy of mitochondria-related diseases.

PMID- 29199242
TI  - A Single-Step "Breeding" Generated a Diagnostic Anti-cortisol Antibody Fragment
      with Over 30-Fold Enhanced Affinity.
AB  - Cortisol levels in bodily fluids represent a useful index for pituitary-adrenal
      function, and thus practical anti-cortisol antibodies are required. We have
      studied "antibody-breeding" approaches, which involve in vitro evolution of
      antibodies to improve their antigen-binding performances. Here, we produced an
      antibody fragment to measure serum cortisol levels with over 30-fold enhanced
      affinity after single mutagenesis and selection steps. A mouse anti-cortisol
      antibody, Ab-CS#3, with insufficient affinity for practical use, was chosen as
      the prototype antibody. A "wild-type" single-chain Fv fragment (wt-scFv; Ka,
      3.4*108 M-1) was prepared by bacterial expression of a fusion gene combining the
      VH and VL genes for this antibody. Then, random point mutations were generated
      separately in VH or VL by error-prone PCR, and the resulting products were used
      to assemble scFv genes, which were displayed on filamentous phages. Repeated
      panning of the phage library identified a mutant scFv (scFv#m1-L10) with an over
      30-fold enhanced affinity (Ka 1.2*1010 M-1). Three amino acid substitutions
      (Cys49Ser, Leu54Pro, and Ser63Gly) were observed in its VL sequence. In a
      competitive enzyme-linked immunosorbent assay (ELISA), the mutant scFv generated
      dose-response curves with measuring range ca. 0.03-0.6 ng/assay cortisol,
      midpoint of which (0.15 ng/assay) was 7.3-fold lower than that of wt-scFv.
      Although cortisone, 11-deoxycortisol, and prednisolone showed considerable cross
      reactivity, the mutant scFv should enable sensitive routine cortisol assays,
      except for measurement after metyrapone or high-dose of prednisolone
      administrations. Actually, cortisol levels of control sera obtained with the scFv
      based ELISA were in the reference range.

PMID- 29199243
TI  - Daphnane and Phorbol Diterpenes, Anti-neuroinflammatory Compounds with Nurr1
      Activation from the Roots and Stems of Daphne genkwa.
AB  - The methanol extract of the roots and stems of Daphne genkwa and its constituents
      yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating
      effects and neuroprotective effects in an animal model of Parkinson's disease
      (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2),
      wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol
      type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)
      acetate (7)) were isolated as Nurr1 activating compounds from the D. genkwa
      extract. Consistent with their higher Nurr1 activating activity, compounds 1, 4,
      5, and 7 exhibited higher inhibitory activity on lipopolysaccharide (LPS)-induced
      nitric oxide (NO) production in murine microglial BV-2 cells with an IC50 (uM) of
      1-2, which was 15-30 times more potent than that of minocycline (29.9 uM), a well
      known anti-neuroinflammatory agent. Additionally, these diterpenes reduced
      expression and transcription of LPS-induced pro-inflammatory cytokines in BV-2
      cells. Thus, the daphnane-type and phorbol-type diterpenes had anti
      neuroinflammatory activity with Nurr1 activation and could be responsible for the
      anti-PD effect of the roots and stems of D. genkwa.

PMID- 29199244
TI  - Errata for Biological and Pharmaceutical Bulletin.

PMID- 29199245
TI  - Primary renal mixed tumor characterized by marked proliferation of osteoblast
      like cells with osteoid formation in a swine.
AB  - Renal mixed tumor characterized by the absence of nephrogenic blastema and the
      presence of predominant osteoid-producing osteoblast-like cells occurred in the
      kidney of a 6-month-old, hybrid, female pig. At the post-mortem examination, the
      tumor was found as a calcified grayish-white mass at the cranial end of the left
      kidney. Histologically the tumor consisted of 3 growth areas of poorly
      differentiated spindle cells, osteoid-producing osteoblast-like cells, and
      luminal epithelial cells. Transition from the spindle cells to the osteoblast
      like cells or the luminal epithelial cells was observed. Immunohistochemically,
      the spindle cells and the osteoblast-like cells were consistently positive for
      beta-catenin. Although the luminal epithelial cells and adjacent spindle cells
      were positive for cytokeratin, these 3 types of tumor cells were consistently
      negative for WT1. The tumor was diagnosed as primary renal mixed tumor
      characterized by marked proliferation of osteoblast-like cells with osteoid
      formation.

PMID- 29199246
TI  - Factors Leading to Improved Gait Function in Patients with Subacute or Chronic
      Central Nervous System Impairments Who Receive Functional Training with the Robot
      Suit Hybrid Assistive Limb.
AB  - The factors that lead to the improvement of gait function in patients with
      diseases of the central nervous system (CNS) who use a hybrid assistive limb
      (HAL) are not yet fully understood. The purpose of the present study was to
      analyze these factors to determine the prognosis of the patients' gait function.
      Patients whose CNS disease was within 180 days since onset were designated as the
      subacute-phase patients, and patients whose disease onset had occurred more than
      180 days previously were designated as chronic-phase patients. Fifteen subacute
      phase patients and 15 chronic-phase patients were given HAL training. The study
      analyzed how post-training walking independence in these patients was affected by
      the following factors: age, disease, lesion area, lower limb function, balance,
      period until the start of training, number of training sessions, additional
      rehabilitation, higher-order cognitive dysfunction, HAL model, and the use of a
      non-weight-bearing walking-aid. In subacute-phase patients, walking independence
      was related to lower limb function (rs = 0.35). In chronic-phase patients, there
      was a statistically significant correlation between post-training walking
      independence and balance (rs = 0.78). In addition, in patients with a severe
      motor dysfunction that was accompanied by inattention and global cognitive
      dysfunction, little improvement occurred, even with double-leg model training,
      because they had difficulty wearing the device. The results demonstrated that the
      factors that improved walking independence post HAL training differed between
      patients with subacute- and chronic-stage CNS diseases. The findings may serve as
      valuable information for future HAL training of patients with CNS diseases.

PMID- 29199247
TI  - Utility of Indocyanine Green Video Angiography for Sylvian Fissure Dissection in
      Subarachnoid Hemorrhage Patients - Sylvian ICG Technique.
AB  - Indocyanine green (ICG) emits fluorescence in the far-red domain under light
      excitation. ICG video angiography (ICG-VA) has been established as a useful
      method to evaluate blood flow in the operative field. We report the usefulness of
      ICG-VA for Sylvian fissure dissection in patients with subarachnoid hemorrhage
      (SAH). Subjects comprised 7 patients who underwent ICG-VA before opening the
      Sylvian fissure during neck clipping for ruptured cerebral aneurysm. We observed
      contrasted Sylvian veins before opening the Sylvian fissure using surgical
      microscopes. This procedure was termed "Sylvian ICG". We observed ICG
      fluorescence quickly in all cases. Sylvian veins that appeared unclear in the
      standard microscopic operative field covered with subarachnoid hemorrhage were
      extremely clearly depicted. These Sylvian ICG findings were helpful in
      identifying entry points and the dissecting course of the Sylvian fissure. At the
      time of clipping, no residual fluorescence from Sylvian ICG was present, and
      aneurysm clipping was not impeded. Sylvian ICG for SAH patients is a novel
      technique to facilitate dissection of the Sylvian fissure. We believe that this
      technique will contribute to improved safety of clipping surgery for ruptured
      aneurysms.

PMID- 29199248
TI  - Progressive Mycotic Celiac Artery Aneurysm Associated With Coagulase-Negative
      Staphylococcal Prosthetic Valve Endocarditis.

PMID- 29199249
TI  - Utility of Single-Photon Emission Computed Tomography/Computed Tomography Fusion
      Imaging With 99 mTc-Pyrophosphate Scintigraphy in the Assessment of Cardiac
      Transthyretin Amyloidosis.

PMID- 29199250
TI  - Ci-AMBP: a highly conserved member of the microglobulin superfamily of proteinase
      inhibitors in grass carp, Ctenopharyngodon idellus.
AB  - A full-length cDNA clone encoding grass carp (Ctenopharyngodon idellus) alpha1
      microglobulin/bikunin precursor (Ci-AMBP) was isolated by subtracted differential
      hybridization screening from a liver cDNA library. The deduced amino acid
      sequence shared approximately 50% sequence identity with its mammalian
      counterparts, but more than 90% identity with another fish species. AMBPs are the
      precursors of the plasma glycoproteins alpha1-microglobulin (alpha1m) and
      bikunin. Both peptide structures and their chromosomal organization were well
      conserved in Ci-AMBP. The alpha1m and bikunin polypeptides are separated by the
      typical tetrapeptide R-A-R-R that provides an endoproteolytic cleavage site for
      maturation. The genetic organization of domains and functional motifs indicated
      that Ci-AMBP is a typical member of the lipocalin and Kunitz-type protease
      inhibitor superfamilies. Expression of the Ci-AMBP gene in different
      tissues/organs was evaluated using semi-quantitative RT-PCR and, in contrast to
      the restricted expression in other species, transcripts were detected in a wide
      range of tissues. The most abundant expression occurred in the secretory organs,
      which supports the roles of alpha1m and bikunin in the immune response to
      diseases and in the stress response.

PMID- 29199251
TI  - [Change Emergency Intensive Care!!Create and Disseminate Evidence That
      Contributes to Improving the Treatment of Critically Ill Patients].

PMID- 29199252
TI  - [Evaluation of Pharmacotherapy on Emergency and Intensive Care Medicine: The
      Influence of Intensity and Duration of Invasion].
AB  - Critically ill patients who receive high-level invasion show physiological
      changes different from those under more normal conditions, along with variable
      therapeutic effects and pharmacokinetics. The concept of systemic inflammatory
      response syndrome (SIRS) has been introduced to describe the clinical state
      resulting from invasive actions taken under acute circumstances, resulting in an
      acute-phase systemic response. In particular, dosages of vancomycin (VCM) and
      phenytoin (PHT) need to be adjusted by therapeutic drug monitoring (TDM) because
      of their narrow therapeutic concentration windows. However, there are few reports
      on the pharmacokinetics of VCM and PHT in patients with SIRS. We performed a
      retrospective cohort study of patients treated with VCM and PHT. These studies
      suggest that the pharmacokinetics of VCM are affected by SIRS score and duration.
      Furthermore, the concentration of PHT was also shown to be higher in SIRS
      patients compared with non-SIRS patients. These findings suggest that the
      pharmacokinetics of VCM and PHT may be affected by the pathology of SIRS, rather
      than by other patient characteristics. Modifying dosing according to SIRS will
      improve the prediction accuracy of drug concentration based on TDM. In this
      review, I introduce work conducted by pharmacists in the clinical study of
      critically ill patients, and will be discussing the evaluation of pharmacotherapy
      in emergency and intensive care medicine.

PMID- 29199253
TI  - [Effects of Pharmacist Intervention on the Treatment of Infectious Diseases in
      Critically Ill Patients].
AB  - The pathological conditions of patients who require intensive care are usually
      complex and extremely severe; their health and life are in a critical state.
      Therefore, correct, rapid treatment of these conditions is indispensable.
      Furthermore, the selection of drugs and adjustment of their dosage for an
      immediate effect are important. Moreover, most patients are immunocompromised and
      present an extremely high level of risk for complications involving infectious
      diseases. Since such complications may lead to life-threatening outcomes, a
      rational dosage regimen to achieve sufficient antimicrobial activity from the
      initial stage of treatment is essential. However, most critically ill cases are
      complicated by several factors: fluid retention including edema, pleural
      effusion, and ascites; increased vascular permeability and hypoalbuminemia; and
      dysfunction of various organs. These factors cause significant changes in the
      pharmacokinetics of antimicrobials, making it particularly difficult to design a
      dosage regimen at the time of initial administration. Thus, we focused on the
      importance of a rational dosage regimen for antimicrobial drugs in the treatment
      of infectious diseases. We conducted a retrospective study of severe cases of
      pneumonia with a high death rate; patients were divided into two groups according
      to the pharmacist intervention procedures and a comparative study of treatment
      efficacy was performed. Furthermore, for antimicrobial agents to exert a
      sufficient effect from the initial stage of treatment, we examined the
      theoretical methodology underlying the initial administration.

PMID- 29199254
TI  - [Drug Repositioning Research Utilizing a Large-scale Medical Claims Database to
      Improve Survival Rates after Cardiopulmonary Arrest].
AB  - Approximately 100000 people suffer cardiopulmonary arrest in Japan every year,
      and the aging of society means that this number is expected to increase.
      Worldwide, approximately 100 million develop cardiac arrest annually, making it
      an international issue. Although survival has improved thanks to advances in
      cardiopulmonary resuscitation, there is a high rate of postresuscitation
      encephalopathy after the return of spontaneous circulation, and the proportion of
      patients who can return to normal life is extremely low. Treatment for
      postresuscitation encephalopathy is long term, and if sequelae persist then
      nursing care is required, causing immeasurable economic burdens as a result of
      ballooning medical costs. As at present there is no drug treatment to improve
      postresuscitation encephalopathy as a complication of cardiopulmonary arrest, the
      development of novel drug treatments is desirable. In recent years, new efficacy
      for existing drugs used in the clinical setting has been discovered, and drug
      repositioning has been proposed as a strategy for developing those drugs as
      therapeutic agents for different diseases. This review describes a large-scale
      database study carried out following a discovery strategy for drug repositioning
      with the objective of improving survival rates after cardiopulmonary arrest and
      discusses future repositioning prospects.

PMID- 29199255
TI  - [Diversity of Secondary Metabolites from Some Medicinal Plants and Cultivated
      Lichen Mycobionts].
AB  - Studies on the structural determination, biosynthesis, and biological activities
      of secondary metabolites from natural sources are significant in the field of
      natural products chemistry. This review focuses on diverse secondary metabolites
      isolated from medicinal plants and cultivated mycobionts of lichens in our
      laboratory. Monoterpene-tetrahydroisoquinoline glycosides and alkaloids isolated
      from Cephaelis acuminata and Alangium lamarckii gave important information on the
      biosynthesis of ipecac alkaloids. A variety of glycosides linked with a
      secologanin unit and indole alkaloids were obtained from medicinal plants
      belonging to the families of Rubiaceae, Apocynaceae, and Loganiaceae. Plant
      species of the four genera Fraxinus, Syringa, Jasminum, and Ligustrum of the
      family Oleaceae were chemically investigated to provide several types of
      secoiridoid and iridoid glucosides. The biosynthetic pathway leading from
      protopine to benzophenanthridine alkaloids in suspension cell cultures of
      Eschscholtzia californica was elucidated. The structures and biological
      activities of the bisbenzylisoquinoline alkaloids of Stephania cepharantha and
      Nelumbo nucifera were also investigated. In addition, the mycobionts of lichens
      were cultivated to afford various types of metabolites that differ from the
      lichen substances of intact lichens but are structurally similar to fungal
      metabolites. The biosynthetic origins of some metabolites were also studied.
      These findings suggest that cultures of lichen mycobionts could be sources of new
      bioactive compounds and good systems for investigating secondary metabolism in
      lichens.

PMID- 29199256
TI  - [Synthesis, Aggregation, Self-assembly, and Dynamic Properties of Helicene
      Oligomers].
AB  - Biological systems exhibit dynamic phenomena at the macroscopic level as a
      result of the hierarchical integration of phenomena at the molecular level. For
      example, a number of amino acids compose actin proteins, which form three
      dimensional structures determined by the sequence of amino acids. They form
      fibers by self-assembly, which then form ordered structures such as meshes,
      lyotropic liquid crystals (LCs), and bundles. The dynamic and reversible
      polymorphism between these nano- to centimeter-sized ordered structures is
      essential for biological functions such as cell division, contraction, and
      locomotion. To understand biological systems and create new functional materials,
      it is essential to develop a methodology to integrate phenomena at the molecular
      level into those at the macroscopic level using synthetic molecules. In this
      research, synthetic oligomers containing helicenes, which exhibit reversible
      structural transitions between cylindrical double helices and random coils in
      response to thermal stimuli, were employed as building blocks for the development
      of such a methodology. The properties of homo- and hetero-double helices at the
      molecular level were first controlled by taking advantage of the diversity of
      their molecular structures. Then, nano- to micrometer-sized structures were
      constructed by the self-assembly of hetero-double helices, which include
      fibers/gels, vesicles, and lyotropic LCs, and their dynamic properties were
      controlled by molecular design.

PMID- 29199257
TI  - [Retinoic Acid Prevents Dendritic Cells from Inducing Novel Inflammatory T Cells
      That Produce Abundant Interleukin-13].
AB  - Vitamin A (VA) plays critical roles in gut homeostasis. Dendritic cells in
      mesenteric lymph nodes (MLN-DCs) can metabolize VA to retinoic acid (RA), thereby
      inducing gut-tropic lymphocytes and enhancing peripheral differentiation of
      regulatory T cells expressing forkhead box P3. We found that MLN-DCs from VA
      deficient mice induced a distinct inflammatory T helper type 2 (Th2)-cell subset
      that produced abundant interleukin-13 (IL-13) and expressed receptors for homing
      to skin and inflammatory sites but not to the intestine. IL-6-neutralizing
      antibodies or RA abrogated the induction of this subset. On the other hand, RA
      receptor antagonists allowed MLN-DCs from VA-sufficient mice to induce a similar
      T-cell subset. IL-6 induced the differentiation of this subset from naive CD4+ T
      cells upon activation with antibodies against CD3 and CD28, and RA receptor
      antagonists enhanced this induction. It has been considered that VA deficiency
      reduces Th2-dependent antibody responses. However, oral administration of an
      antigen to VA-deficient mice failed to induce immune tolerance but primed strong
      IL-13-dependent immunoglobulin G1 (IgG1) responses and IgE responses that caused
      skin allergy. These results suggest that MLN-DCs possess the latent ability to
      induce IL-13-producing inflammatory Th2 cells and that RA prevents them from
      inducing IL-13-dependent allergic or inflammatory responses to orally
      administered antigens.

PMID- 29199258
TI  - [Research on Insufficient Information for Pharmaceutical Products].
AB  - Several issues concerning medicines remain unclear, including the availability
      of known, but not easily recognizable information. This review evaluates the
      mechanisms of side effects and the various risk indications included in package
      inserts. The results can be summarized as follows. 1) Short-term exposure to
      gatifloxacin significantly induced insulin secretion and increased the cytosolic
      Ca2+ concentration of islet cells by augmenting extracellular Ca2+ influx and its
      release from the endoplasmic reticulum. Alternatively, there was a decline in the
      cellular insulin level and reactivity to sulfonylurea after prolonged exposure.
      The insulin depletion was greater than that produced by other fluoroquinolones.
      2) The elution of di(2-ethylhexyl)phthalate (DEHP) from the infusion set could be
      associated with the solubilizers in the injection medicines. The package inserts
      of several products containing polysorbate or ethanol had no warning about DEHP.
      Although there was a slight correlation between polysorbate content and
      descriptions on package inserts, the use of DEHP-containing devices was
      prohibited for some products, even with limited amounts of polysorbate.
      Therefore, the package insert statements should be reviewed to reflect
      appropriately the extent of DEHP elution. 3) Risk management plan consists of
      strategies to minimize the potential risks of medicines. One approach could be to
      introduce reminders on package inserts; however, of 268 potential risks
      associated with 81 products, 56 were not mentioned in package inserts. Because
      most postmarketing pharmacovigilance plans depend on spontaneous reporting by
      healthcare personnel, the descriptions on package inserts should be reexamined.

PMID- 29199259
TI  - [Development of Novel Functional Molecules Based on the Molecular Structure
      Characteristics of Diketopiperazines].
AB  - This article focuses on our investigation of the molecular structure
      characteristics of diketopiperazines (DKPs), and application of these findings to
      the development of novel functional molecules. DKPs bearing a benzyl moiety are
      known to adopt a folded conformation, in which the benzyl moiety is folded over
      the DKP ring. In order to investigate the driving force behind the folded
      conformation, we synthesized DKPs bearing a benzyl moiety with different para
      substituents, and demonstrated that the folded conformation likely arose from
      intramolecular CH/pi interactions, based on the electronic effects of para
      substituents on the benzyl group in 1H NMR spectroscopy. On the other hand, N4
      methylation of DKPs bearing a benzyl moiety was found to change their folded
      conformation to an extended conformation, based on single crystal X-ray
      crystallography and 1H NMR spectroscopy analysis. Next, we attempted to
      synthesize both hydroxamate-type siderophores containing the DKP ring:
      rhodotorulic acid and erythrochelin. Facile synthesis of rhodotorulic acid and
      its N,N'-dimethylated derivative was achieved by microwave-assisted cyclization
      of the corresponding dipeptide precursors. Interestingly, N,N'-dimethylated
      rhodotorulic acid was found to be more soluble in various organic solvents than
      rhodotorulic acid. Moreover, erythrochelin was synthesized for the first time,
      and its metal-chelating ability with not only Fe(III) but also Mg(II) was
      confirmed based on electrospray ionization mass spectrometry (ESI-MS) analysis.
      Finally, we synthesized DKPs bearing a primary amino group, and found that they
      could catalyze the asymmetric aldol reaction between hydroxyacetone and p
      nitrobenzaldehyde.

PMID- 29199260
TI  - [Implementation and Evaluation of Genetic Testing Seminars about Lifestyle
      related Disease Prevention in Pharmacy Insurance-The Need for Cooperation between
      the Pharmacy and the University in Genetic Testing].
AB  - A seminar titled "Implementation and evaluation of genetic testing of lifestyle
      related disease genes" was held for pharmacists, medical clerks, and clerks of
      pharmacy insurance, with the aim of holding seminars led by pharmacists for the
      general public (including patients) in the future. The subject of the seminar was
      single nucleotide polymorphisms in obesity-related genes and alcohol metabolism
      related genes. The purpose of the seminar was to contribute to the prevention of
      lifestyle-related diseases of the general public. We evaluated it by
      administering a questionnaire to the participants before and after the seminar.
      After the seminar, 55% of pharmacists answered that they would like to or would
      strongly like to participate in genetic testing (for lifestyle-related diseases
      and drug metabolism-related genes) of the general public. However, some
      participants did not wish to do so. A customer satisfaction (CS) analysis found
      that this was mainly because they did not want to know the results of genetic
      testing of others, which they felt should be private. Most (82%) of the
      pharmacists answered that assistance and advice was "very necessary" or
      "necessary" in the participation of genetic testing. These findings show that
      collaboration between pharmacies and universities will be important for future
      seminars to the general public.

PMID- 29199262
TI  - Impaired Bioenergetics in Clinical Medicine: A Target to Tackle.
AB  - Mitochondrial energy deficit is considered a key element of different clinical
      pathologies - from inherited disorders of energy metabolism to drug-induced
      mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases.
      However, clinical manifestations of impaired bioenergetics are not easy to
      recognize, with patient-reported features usually include non-pathognomonic
      fatigue and weakness, or exercise intolerance, while specific lab tests are
      missing. Although it is not clear whether poor energetics is a primary deficit or
      a secondary consequence of specific disorders, improving mitochondrial viability
      remains a challenging task in both experimental and clinical medicine. In this
      review, biochemical and clinical evidence of energy deficits were reviewed, along
      with possible therapeutic options to tackle energy failure and restore
      bioenergetics.

PMID- 29199261
TI  - TBX19 is overexpressed in colorectal cancer and associated with lymph node
      metastasis.
AB  - The T-box 19 (TBX19) gene encodes a transcription factor characterized by a
      highly conserved DNA-binding motif (T-box). Recent studies have revealed that
      TBX19 has been identified as one of the genes activated by KRAS mutations, and is
      upregulated in colon adenoma. These results indicate that TBX19 may work as an
      oncogene in colorectal cancer (CRC). However, the expression and role of TBX19
      have yet to be investigated. Here, we investigated TBX19 mRNA and protein
      expressions in colon cancer cells or surgically resected CRC. We found that TBX19
      mRNA expression was significantly increased in tumorous tissues compared to that
      in non-tumorous tissues, and increased TBX19 mRNA expression was associated with
      positive lymph node metastasis in our cohort. The expression of TBX19 mRNA was
      not correlated with that of TBX19 protein in tissue sample taken from the CRC
      patients. Moreover, TBX19 showed positive staining even in the normal colonic
      tissues and the adjacent non-tumorous tissues. These results suggest that the
      expression of TBX19 protein is not correlated with the expression of TBX19 mRNA.
      In addition, our results promote further investigations into the impact of TBX19
      upregulation on colorectal carcinogenesis, as well as the underlying mechanisms.

PMID- 29199263
TI  - Determination of crystalline silica in respirable dust upon occupational exposure
      for Egyptian workers.
AB  - Crystalline free silica is considered as a lung carcinogen and the occupational
      exposure to its dust is a health hazard to workers employed in industries that
      involve ores of mineral dust. In Egypt, thousands of people work under conditions
      of silica dust exposure exceeding the occupational exposure limit, as a result
      the monitoring of this occupational exposure to crystalline silica dust is
      required by government legislation. The assessment of the later is a multi-phase
      process, depend on workplace measurements, quantitative analyses of samples, and
      comparison of results with the permissible limits. This study aims to investigate
      occupational exposure to crystalline silica dust at 22 factories in Egypt with
      different industrial activities like stone cutting, glass making, ceramic, and
      sand blasting. Dust samples were collected from work sites at the breathing zone
      using a personal sampling pump and a size-selective cyclone and analyzed using
      FTIR. The sampling period was 60-120 min. The results show that the exposure at
      each of the industrial sectors is very much higher than the current national and
      international limits, and that lead to a great risk of lung cancer and mortality
      to workers.

PMID- 29199264
TI  - Organophosphorus pesticide exposure in agriculture: effects of temperature,
      ultraviolet light and abrasion on PVC gloves.
AB  - Elbow length PVC gloves are often recommended for protection against
      organophosphorus pesticide (OP) exposure in agriculture. However, performance may
      be reduced due to high temperature, UV exposure and abrasion. We sought to assess
      these impacts for two OPs under normal use and reasonable worst-case scenarios.
      Glove permeation tests were conducted using ASTM cells with two PVC glove brands
      at 23 degrees C and 45 degrees C for up to 8 h. Technical grade dichlorvos and
      formulated diazinon were used undiluted and at application strength. Breakthough
      of undiluted dichlorvos occurred at both 23 degrees C and 45 degrees C, but only
      at 45 degrees C for application strength. Breakthrough of diazinon was not
      achieved, except when undiluted at 45 degrees C. UV-exposed and abraded gloves
      showed reduced performance, with the effect being approximately two-fold for
      dichlorvos. Only small differences were noted between glove brands. Extra
      precautions should be taken when handling concentrated OPs at high temperature,
      or when using abraded or sunlight-exposed gloves.

PMID- 29199265
TI  - Standard Values and Characteristics of Electrocardiographic Findings in Children
      and Adolescents.
AB  - BACKGROUND: Reference values and the characteristics of the electrocardiographic
      (ECG) findings using a large number of subjects are lacking for children and
      adolescents.Methods and Results:A total of 56,753 digitally stored ECGs of
      participants in a school-based ECG screening system were obtained between 2006
      and 2009 in Kagoshima, Japan. Each ECG was manually reviewed by 2 pediatric
      cardiologists and only ECGs with sinus rhythm were included. A final total of
      48,401 ECGs from 16,773 1st (6 years old, 50% girls), 18,126 7th (12 years old,
      51% girls), and 13,502 10th graders (15 years old, 52% girls) were selected. ECG
      variables showed differences in age and sex. However, the effects of age and sex
      on ECG variables such as the PQ interval, QRS voltage, and STJ segment were also
      different. The 98th percentile values of well-known surrogate parameters for
      ventricular hypertrophy in the present study were much higher than the
      conventional criteria. CONCLUSIONS: The present study of a large number of
      pediatric subjects showed that the effects of age and sex on ECG parameters are
      different, and that criteria for ventricular hypertrophy should be newly
      determined by age and sex. We have developed reference data for STJ segment
      elevation for children and adolescents. These findings are useful for creating
      guidelines and recommendations for interpretation of pediatric ECG.

PMID- 29199266
TI  - Diagnosis and Management of Spontaneously Recanalized Coronary Thrombus Guided by
      Optical Coherence Tomography - Lessons From the French "Lotus Root" Registry.
AB  - BACKGROUND: Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in
      autopsy series, but little is known about SRCT, and it is potentially under
      diagnosed in clinical practice.Methods and Results:SRCT identified on OCT were
      included in a French multicenter series, the Lotus Root French Registry. A total
      of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years;
      IQR, 52-65 years); 23/33 patients (70%) presented with angina pectoris and/or
      dyspnea. Three angiographic aspects were distinguished retrospectively: braided,
      pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis
      varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on
      OCT varied between 20% and 92% (median, 68%). A typical "lotus root" aspect was
      confirmed on OCT, consisting of multiple circular concave-edged channels of
      varying size, numbering between 3 and 12 depending on the slice, separated by
      smooth-edged septa of high luminosity without posterior attenuation. OCT also
      served to guide treatment, with stenting in 91% of cases. During the 17-month
      follow-up 91% of patients had excellent evolution. One death and 3 ACS events
      occurred. CONCLUSIONS: In this large SRCT cohort, angiography had limited
      diagnostic value whereas OCT could be used to define disease characteristics and
      guide treatment of lesions inducing angina pectoris and/or silent myocardial
      ischemia. OCT-guided management was associated with good prognosis.

PMID- 29199267
TI  - High-Frequency Color Doppler Ultrasound in Diagnosis, Treatment, and
      Rehabilitation of Achilles Tendon Injury.
AB  - BACKGROUND This study evaluated the clinical application of high-frequency color
      Doppler ultrasonography (HFCDU) in the diagnosis, treatment, and rehabilitation
      of Achilles tendon injury. MATERIAL AND METHODS A total of 68 patients with
      suspected Achilles tendon injury were examined by HFCDU. There were 42 Achilles
      tendon injury patients who underwent surgery, and they were randomly divided into
      a routine treatment group (n=21) and a rehabilitation group (n=21). HFCDU was
      performed at weeks 1, 3, 6, and 9, and months 3, 6, 9, 12, and 24 after the
      operation. The thickness of the injured Achilles tendon, echo, blood flow, and
      tissue adhesion were compared to those of the uninjured side. RESULTS Of the 68
      patients, 14 had normal ultrasound presentation with strong echo; 7 had
      laceration, presenting as swelling and decreased echo; 26 had partial tear,
      presenting as discontinued rupture with no or low echo; 19 had complete rupture,
      presenting as discontinued fibers with hypoechoic hemorrhage and hyperechoic fat
      tissue between ends; 1 had plantar tendon rupture and periapical hemorrhage; and
      1 had acute Achilles tendonitis. The postoperative tendon thickness decreased
      over time, echo turned homogeneous, blood flow and adhesions decreased, and these
      results were consistent with clinical symptoms. Patient condition and ultrasound
      recovery were better in the rehabilitation group, and the diameter of the injured
      tendon increased compared with the uninjured side. CONCLUSIONS HFCDU can
      determine the types and extent of tendon injuries, and can help in the diagnosis,
      treatment, and rehabilitation of Achilles tendon injury.

PMID- 29199268
TI  - A Rare Case of Giant Basal Cell Carcinoma of the Abdominal Wall: Excision and
      Immediate Reconstruction with a Pedicled Deep Inferior Epigastric Artery
      Perforator (DIEP) Flap.
AB  - BACKGROUND Basal cell carcinoma (BCC) greater than 5 cm in diameter is called
      giant basal cell carcinoma (GBCC), or super giant basal cell carcinoma if it has
      a diameter larger than 20 cm. Giant BCC only accounts for 0.5% of BCCs and super
      giant BCC is exceedingly rare. On account of their rarity, there are no
      established guidelines for GBCC treatment. CASE REPORT We describe a peculiar
      case of an 82-year-old woman with a GBCC carcinoma of the lower abdominal wall.
      The tumor was surgically removed with ipsilateral inguinal lymph nodes and the
      abdominal wall was reconstructed immediately with a pedicled deep inferior
      epigastric artery perforator (DIEP) flap. CONCLUSIONS Treatment of giant basal
      cell carcinoma is often difficult, especially in elderly patients with poor
      general health and multiple pathologies. The pedicled DIEP flap is rotated to
      cover the loss of substance without tension, and it is easy to harvest and
      transfer. This flap allowed a good result without local or systemic complication.
      We present this report as a reminder of the occasional occurrence of extremely
      aggressive BCCs. We believe that, especially for rare tumors like these, it is
      very useful for the entire scientific community to publish these cases and the
      therapeutic strategies used to treat them.

PMID- 29199271
TI  - Random access quantum information processors using multimode circuit quantum
      electrodynamics.
AB  - Qubit connectivity is an important property of a quantum processor, with an ideal
      processor having random access-the ability of arbitrary qubit pairs to interact
      directly. This a challenge with superconducting circuits, as state-of-the-art
      architectures rely on only nearest-neighbor coupling. Here, we implement a random
      access superconducting quantum information processor, demonstrating universal
      operations on a nine-qubit memory, with a Josephson junction transmon circuit
      serving as the central processor. The quantum memory uses the eigenmodes of a
      linear array of coupled superconducting resonators. We selectively stimulate
      vacuum Rabi oscillations between the transmon and individual eigenmodes through
      parametric flux modulation of the transmon frequency. Utilizing these
      oscillations, we perform a universal set of quantum gates on 38 arbitrary pairs
      of modes and prepare multimode entangled states, all using only two control
      lines. We thus achieve hardware-efficient random access multi-qubit control in an
      architecture compatible with long-lived microwave cavity-based quantum memories.

PMID- 29199269
TI  - Dendrogenin A drives LXR to trigger lethal autophagy in cancers.
AB  - Dendrogenin A (DDA) is a newly discovered cholesterol metabolite with tumor
      suppressor properties. Here, we explored its efficacy and mechanism of cell death
      in melanoma and acute myeloid leukemia (AML). We found that DDA induced lethal
      autophagy in vitro and in vivo, including primary AML patient samples,
      independently of melanoma Braf status or AML molecular and cytogenetic
      classifications. DDA is a partial agonist on liver-X-receptor (LXR) increasing
      Nur77, Nor1, and LC3 expression leading to autolysosome formation. Moreover, DDA
      inhibited the cholesterol biosynthesizing enzyme 3beta-hydroxysterol-Delta8,7
      isomerase (D8D7I) leading to sterol accumulation and cooperating in autophagy
      induction. This mechanism of death was not observed with other LXR ligands or
      D8D7I inhibitors establishing DDA selectivity. The potent anti-tumor activity of
      DDA, its original mechanism of action and its low toxicity support its clinical
      evaluation. More generally, this study reveals that DDA can direct control a
      nuclear receptor to trigger lethal autophagy in cancers.

PMID- 29199270
TI  - Mechanism of early light signaling by the carboxy-terminal output module of
      Arabidopsis phytochrome B.
AB  - Plant phytochromes are thought to transduce light signals by mediating the
      degradation of phytochrome-interacting transcription factors (PIFs) through the N
      terminal photosensory module, while the C-terminal module, including a histidine
      kinase-related domain (HKRD), does not participate in signaling. Here we show
      that the C-terminal module of Arabidopsis phytochrome B (PHYB) is sufficient to
      mediate the degradation of PIF3 specifically and to activate photosynthetic genes
      in the dark. The HKRD is a dimerization domain for PHYB homo and
      heterodimerization. A D1040V mutation, which disrupts the dimerization of HKRD
      and the interaction between C-terminal module and PIF3, abrogates PHYB nuclear
      accumulation, photobody biogenesis, and PIF3 degradation. By contrast, disrupting
      the interaction between PIF3 and PHYB's N-terminal module has little effect on
      PIF3 degradation. Together, this study demonstrates that the dimeric form of the
      C-terminal module plays important signaling roles by targeting PHYB to subnuclear
      photobodies and interacting with PIF3 to trigger its degradation.

PMID- 29199272
TI  - Dissipatively coupled waveguide networks for coherent diffusive photonics.
AB  - A photonic circuit is generally described as a structure in which light
      propagates by unitary exchange and transfers reversibly between channels. In
      contrast, the term 'diffusive' is more akin to a chaotic propagation in
      scattering media, where light is driven out of coherence towards a thermal
      mixture. Based on the dynamics of open quantum systems, the combination of these
      two opposites can result in novel techniques for coherent light control. The
      crucial feature of these photonic structures is dissipative coupling between
      modes, via an interaction with a common reservoir. Here, we demonstrate
      experimentally that such systems can perform optical equalisation to smooth
      multimode light, or act as a distributor, guiding it into selected channels.
      Quantum thermodynamically, these systems can act as catalytic coherent reservoirs
      by performing perfect non-Landauer erasure. For lattice structures, localised
      stationary states can be supported in the continuum, similar to compacton-like
      states in conventional flat-band lattices.

PMID- 29199273
TI  - MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand
      epiregulin and its transcriptional inducer HOXB9.
AB  - Growing evidence suggests that microRNAs are involved in the development and
      progression of colorectal cancer (CRC). In the present study, deregulation and
      functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448
      tumor tissues and 325 paired adjacent healthy tissues collected from Czech and
      Spain cohorts of CRC patients have been used for miR-215-5p expression analyses.
      A series of in vitro experiments have been performed using transient transfection
      of miR-215-5p mimics into four CRC cell lines to identify specific cellular
      processes affected by miR-215-5p. Further, the effects of miR-215-5p on tumor
      growth were evaluated in vivo using NSG mice and stable cell line overexpressing
      miR-215-5p. Target mRNAs of miR-215-5p were tested using luciferase assay and
      western blot analyses. We found that miR-215-5p is significantly downregulated in
      tumor tissues compared with non-tumor adjacent tissues and its decreased levels
      correlate with the presence of lymph node metastases, tumor stage, and shorter
      overall survival in CRC patients. Overexpression of miR-215-5p significantly
      reduced proliferation, clonogenicity, and migration of CRC cells, lead to cell
      cycle arrest in G2/M phase and p53-dependent induction of apoptosis. The ability
      of miR-215-5p to inhibit tumor growth was confirmed in vivo. Finally, we
      confirmed epiregulin and HOXB9 to be the direct targets of miR-215-5p. As
      epiregulin is EGFR ligand and HOXB9 is its transcriptional inducer, we suggest
      that the main molecular link between miR-215-5p and CRC cells phenotypes presents
      the EGFR signaling pathway, which is one of the canonical pathogenic pathways in
      CRC.

PMID- 29199275
TI  - Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by
      biophysical and cellular studies.
AB  - Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) contributes to endosomal
      and lysosomal function. LIMP-2 deficiency is associated with neurological
      abnormalities and kidney failure and, as an acid glucocerebrosidase receptor,
      impacts Gaucher and Parkinson's diseases. Here we report a crystal structure of a
      LIMP-2 luminal domain dimer with bound cholesterol and phosphatidylcholine.
      Binding of these lipids alters LIMP-2 from functioning as a glucocerebrosidase
      binding monomer toward a dimeric state that preferentially binds anionic
      phosphatidylserine over neutral phosphatidylcholine. In cellular uptake
      experiments, LIMP-2 facilitates transport of phospholipids into murine
      fibroblasts, with a strong substrate preference for phosphatidylserine. Taken
      together, these biophysical and cellular studies define the structural basis and
      functional importance of a form of LIMP-2 for lipid trafficking. We propose a
      model whereby switching between monomeric and dimeric forms allows LIMP-2 to
      engage distinct binding partners, a mechanism that may be shared by SR-BI and
      CD36, scavenger receptor proteins highly homologous to LIMP-2.

PMID- 29199279
TI  - Chemokines: Moving on up.

PMID- 29199278
TI  - Pharmacology: Investigating nephrotoxicity with an integrated liver-kidney chip.

PMID- 29199274
TI  - Recent developments in genetics and medically assisted reproduction: from
      research to clinical applications.
AB  - Two leading European professional societies, the European Society of Human
      Genetics and the European Society for Human Reproduction and Embryology, have
      worked together since 2004 to evaluate the impact of fast research advances at
      the interface of assisted reproduction and genetics, including their application
      into clinical practice. In September 2016, the expert panel met for the third
      time. The topics discussed highlighted important issues covering the impacts of
      expanded carrier screening, direct-to-consumer genetic testing, voiding of the
      presumed anonymity of gamete donors by advanced genetic testing, advances in the
      research of genetic causes underlying male and female infertility, utilisation of
      massively parallel sequencing in preimplantation genetic testing and non-invasive
      prenatal screening, mitochondrial replacement in human oocytes, and additionally,
      issues related to cross-generational epigenetic inheritance following IVF and
      germline genome editing. The resulting paper represents a consensus of both
      professional societies involved.

PMID- 29199280
TI  - Vaccines in 2017: Closing in on a Zika virus vaccine.

PMID- 29199277
TI  - The renaissance of complement therapeutics.
AB  - The increasing number of clinical conditions that involve a pathological
      contribution from the complement system - many of which affect the kidneys - has
      spurred a regained interest in therapeutic options to modulate this host defence
      pathway. Molecular insight, technological advances, and the first decade of
      clinical experience with the complement-specific drug eculizumab, have
      contributed to a growing confidence in therapeutic complement inhibition. More
      than 20 candidate drugs that target various stages of the complement cascade are
      currently being evaluated in clinical trials, and additional agents are in
      preclinical development. Such diversity is clearly needed in view of the complex
      and distinct involvement of complement in a wide range of clinical conditions,
      including rare kidney disorders, transplant rejection and haemodialysis-induced
      inflammation. The existing drugs cannot be applied to all complement-driven
      diseases, and each indication has to be assessed individually. Alongside
      considerations concerning optimal points of intervention and economic factors,
      patient stratification will become essential to identify the best complement
      specific therapy for each individual patient. This Review provides an overview of
      the therapeutic concepts, targets and candidate drugs, summarizes insights from
      clinical trials, and reflects on existing challenges for the development of
      complement therapeutics for kidney diseases and beyond.

PMID- 29199281
TI  - Emerging viral diseases from a vaccinology perspective: preparing for the next
      pandemic.
AB  - Emerging infectious diseases will continue to threaten public health and are
      sustained by global commerce, travel and disruption of ecological systems. Most
      pandemic threats are caused by viruses from either zoonotic sources or vector
      borne sources. Developing better ways to anticipate and manage the ongoing
      microbial challenge will be critical for achieving the United Nations Sustainable
      Development Goals and, conversely, each such goal will affect the ability to
      control infectious diseases. Here we discuss how technology can be applied
      effectively to better prepare for and respond to new viral diseases with a focus
      on new paradigms for vaccine development.

PMID- 29199276
TI  - Immunologic and endocrine functions of adipose tissue: implications for kidney
      disease.
AB  - Excess adiposity can induce adverse sequelae in multiple cell types and organ
      systems. The transition from the lean to the obese state is characterized by
      fundamental cellular changes at the level of the adipocyte. These changes affect
      the local microenvironment within the respective adipose tissue but can also
      affect nonadipose systems. Adipocytes within fat pads respond to chronic nutrient
      excess through hyperplasia or hypertrophy, which can differentially affect
      interorgan crosstalk between various adipose depots and other organs. This
      crosstalk is dependent on the unique ability of the adipocyte to coordinate
      metabolic adjustments throughout the body and to integrate responses to maintain
      metabolic homeostasis. These actions occur through the release of free fatty
      acids and metabolites during times of energy need - a process that is altered in
      the obese state. In addition, adipocytes release a wide array of signalling
      molecules, such as sphingolipids, as well as inflammatory and hormonal factors
      (adipokines) that are critical for interorgan crosstalk. The interactions of
      adipose tissue with the kidney - referred to as the adipo-renal axis - are
      important for normal kidney function as well as the response of the kidney to
      injury. Here, we discuss the mechanistic basis of this interorgan crosstalk,
      which clearly has great therapeutic potential given the increasing rates of
      chronic kidney disease secondary to obesity and type 2 diabetes mellitus.

PMID- 29199282
TI  - Pathogen genomics: Genomics in the time of cholera.

PMID- 29199284
TI  - Stem cells: Regenerating the skin of a young patient.

PMID- 29199285
TI  - Gene expression: SPOTting single RNA molecules transcriptome-wide.

PMID- 29199286
TI  - Batteries for electric road vehicles.
AB  - The dependence of modern society on the energy stored in a fossil fuel is not
      sustainable. An immediate challenge is to eliminate the polluting gases emitted
      from the roads of the world by replacing road vehicles powered by the internal
      combustion engine with those powered by rechargeable batteries. These batteries
      must be safe and competitive in cost, performance, driving range between charges,
      and convenience. The competitive performance of an electric car has been
      demonstrated, but the cost of fabrication, management to ensure safety, and a
      short cycle life have prevented large-scale penetration of the all-electric road
      vehicle into the market. Low-cost, safe all-solid-state cells from which dendrite
      free alkali-metal anodes can be plated are now available; they have an operating
      temperature range from -20  degrees C to 80  degrees C and they permit the design
      of novel high-capacity, high-voltage cathodes providing fast charge/discharge
      rates. Scale-up to large multicell batteries is feasible.

PMID- 29199283
TI  - Am I ready for CRISPR? A user's guide to genetic screens.
AB  - Exciting new technologies are often self-limiting in their rollout, as access to
      state-of-the-art instrumentation or the need for years of hands-on experience,
      for better or worse, ensures slow adoption by the community. CRISPR technology,
      however, presents the opposite dilemma, where the simplicity of the system
      enabled the parallel development of many applications, improvements and
      derivatives, and new users are now presented with an almost paralyzing abundance
      of choices. This Review intends to guide users through the process of applying
      CRISPR technology to their biological problems of interest, especially in the
      context of discovering gene function at scale.

PMID- 29199287
TI  - Polysulfide intercalation in bilayer-structured graphitic C3N4: a first
      principles study.
AB  - Lithium-sulfur (Li-S) batteries have attracted increasing attention due to their
      high theoretical capacity, being a promising candidate for portable electronics,
      electric vehicles and large-scale energy storage. The interactions of bilayer
      structured graphitic C3N4 (bi-C3N4) with S8, lithium polysulfides (LiPSs), 1,3
      dioxolane, 1,2-dimethoxyethane and tetrahydrofuran ether-based solvents have been
      studied using first-principles calculations. It has been found that the
      (micropore-scale) interlayer of bi-C3N4 shows intimate contact and strong binding
      with S8 and LiPSs due to the formation of chemical Li-N bonds. The incorporation
      of soluble LiPSs by the wrinkled layers of bi-C3N4 with 5.5-7.2 A interlayer
      pores can suppress the shuttling effect. The interlayer ultramicropores with
      interlayer distances of <4 A can accommodate the small Li2S2 and Li2S molecules,
      and impede the irreversible reaction between the solvents and the LiPSs. The
      calculated energy gap of bi-C3N4 decreases to be narrow during lithiation. Our
      results can provide a guideline for promoting the electrochemical performance of
      microporous g-C3N4/sulfur composites for Li-S batteries.

PMID- 29199288
TI  - Protonation of N2O and NO2 in a solid phase.
AB  - Adsorption of gaseous N2O on the acidic surface Bronsted centers of the strongest
      known solid acid, H(CHB11F11), results in formation of the N=N-OH+ cation. Its
      positive charge is localized mainly to the H-atom, which is H-bonded to the
      CHB11F11- anion forming an asymmetric proton disolvate of the L1-H+L2 type, where
      L1 = N2O and L2 = CHB11F11-. NO2 protonation under the same conditions leads to
      the formation of the highly reactive cation radical NO2H+, which reacts rapidly
      with an NO2 molecule according to the equation N2OH+ + NO2 -> [N2O4H+] -> N2OH+ +
      O2 resulting in the formation of two types of N2OH+ cations: (i) a typical
      Bronsted superacid, N[triple bond, length as m-dash]N-OH+, with a strongly acidic
      OH group involved in a rather strong H-bond with the anion, and (ii) a typical
      strong Lewis acid, N[triple bond, length as m-dash]N+-OH, with a positive charge
      localized to the central N atom and ionic interactions with the surrounding
      anions via the charged central N atom.

PMID- 29199289
TI  - Design of a catalyst through Fe doping of the boron cage B10H14 for CO2
      hydrogenation and investigation of the catalytic character of iron hydride (Fe
      H).
AB  - The innovative catalyst Fe@B10H14 is designed through Fe doping of the boron cage
      B10H14 and is employed to catalyze CO2 hydrogenation using a quantum mechanical
      method. First, the structure of the Fe@B10H14 complex is characterized through
      calculated 11B NMR chemical shifts and Raman spectra, and the interactions
      between Fe and the four H atoms of the opening in the cage are analyzed, which
      show that various iron hydride (Fe-H) characteristics exist. Subsequently, the
      potential of Fe@B10H14 as a catalyst for the hydrogenative reduction of CO2 in
      the gas phase is computationally evaluated. We find that an equivalent of
      Fe@B10H14 can consecutively reduce double CO2 to obtain the double product HCOOH
      through a two-step reduction, and Fe@B10H12 and Fe@B10H10 are successively
      obtained. The Fe presents single-atom character in the reduction of CO2, which is
      different from the common iron(ii) catalyzed CO2 reduction. The calculated total
      free energy barrier of the first CO2 reduction is only 8.79 kcal mol-1, and that
      of the second CO2 reduction is 25.71 kcal mol-1. Every reduction reaction
      undergoes two key transition states TSC-H and TSO-H. Moreover, the transition
      state of the C-H bond formation TSC-H is the rate-determining step, where the
      interaction between piC[double bond, length as m-dash]O* and the weak sigmaFe-H
      bond plays an important role. Furthermore, the hydrogenations of Fe@B10H12 and
      Fe@B10H10 are investigated, which aim at determining the ability of Fe-H
      circulation in the Fe doped decaborane complex. We find that the hydrogenation of
      Fe@B10H10 undergoes a one-step H2-adsorbed transition state TSH-adsorb with an
      energy barrier of 6.42 kcal mol-1 from Fe@B10H12. Comparing with the
      hydrogenation of Fe@B10H10, it is slightly more difficult for the hydrogenation
      of Fe@B10H12, where the rate-determining step is the H2-cleaved transition state
      TS2H-H with an energy barrier of 17.38 kcal mol-1.

PMID- 29199291
TI  - Geo-material surface modification of microchips using layer-by-layer (LbL)
      assembly for subsurface energy and environmental applications.
AB  - A key constraint in the application of microfluidic technology to subsurface flow
      and transport processes is the surface discrepancy between microchips and the
      actual rocks/soils. This research employs a novel layer-by-layer (LbL) assembly
      technology to produce rock-forming mineral coatings on microchip surfaces. The
      outcome of the work is a series of 'surface-mimetic micro-reservoirs (SMMR)' that
      represent multi-scales and multi-types of natural rocks/soils. For demonstration,
      the clay pores of sandstones and mudrocks are reconstructed by representatively
      coating montmorillonite and kaolinite in polydimethylsiloxane (PDMS) microchips
      in a wide range of channel sizes (width of 10-250 MUm, depth of 40-100 MUm) and
      on glass substrates. The morphological and structural properties of mineral
      coatings are characterized using a scanning electron microscope (SEM), optical
      microscope and profilometer. The coating stability is tested by dynamic flooding
      experiments. The surface wettability is characterized by measuring mineral oil
      water contact angles. The results demonstrate the formation of nano- to micro
      scale, fully-covered and stable mineral surfaces with varying wetting properties.
      There is an opportunity to use this work in the development of microfluidic
      technology-based applications for subsurface energy and environmental research.

PMID- 29199292
TI  - Laboratory study of mass transfer from diluted bitumen trapped in gravel.
AB  - Diluted bitumen (dilbit) spilled to rivers has the potential to sink and become
      trapped in coarse bed sediments. Hyporheic flow through the river bed can then
      lead to the dissolution of hydrocarbons from this trapped oil, and subsequent
      risks to water quality and aquatic life. It is important to understand the
      concentrations of dissolved hydrocarbons in water, relative to aqueous
      solubility, that may result from mass transfer under these conditions,
      particularly under conditions where coarse sediments lead to faster hyporheic
      flow that could promote rate-limited mass transfer conditions. In this study, the
      dissolution of dilbit (Cold Lake Blend) trapped in gravel was measured using one
      dimensional columns at flow rates representative of fast hyporheic flow.
      Dissolved concentrations in the column effluent were found to be less than 20% of
      effective solubility (equilibrium) concentrations and decreased with increasing
      flow rate, indicative of rate-limited conditions. These results show that risks
      posed by the contamination of gravel-bedded rivers by trapped dilbit may be
      lower, but persist for a longer period of time, than those estimated assuming
      dissolution at concentrations near solubility limits.

PMID- 29199294
TI  - An ambiphilic phosphine/H-bond donor ligand and its application to the gold
      mediated cyclization of propargylamides.
AB  - We describe the synthesis of an ambiphilic phosphine/H-bond donor ligand
      featuring a trifluoroacetamide functionality, its coordination to gold(i)
      chloride, and its application as a self-activating catalyst for the cyclization
      of propargylamides.

PMID- 29199295
TI  - Computational investigations of electronic structure modifications of ferrocene
      terminated self-assembled monolayers: effects of electron donating/withdrawing
      functional groups attached on the ferrocene moiety.
AB  - The electrochemical properties of chemically modified electrodes have long been a
      significant focus of research. Although the electronic states are directly
      related to the electrochemical properties, there have been only limited
      systematic efforts to reveal the electronic structures of adsorbed redox
      molecules with respect to the local environment of the redox center. In this
      study, density functional theory (DFT) calculations were performed for ferrocene
      terminated self-assembled monolayers with different electron-donating abilities,
      which can be regarded as the simplest class of chemically modified electrodes. We
      revealed that the local electrostatic potentials, which are changed by the
      electron donating/withdrawing functional groups at the ferrocene moiety and the
      dipole field of coadsorbed inert molecules, practically determine the density of
      states derived from the highest occupied molecular orbital (HOMO) and its
      vicinities (HOMO-1 and HOMO-2) with respect to the electrode Fermi level.
      Therefore, to design new, sophisticated electrodes with chemical modification,
      one should consider not only the electronic properties of the constituent
      molecules, but also the local electrostatic potentials formed by these molecules
      and coadsorbed inert molecules.

PMID- 29199296
TI  - Computational study on the luminescence quantum yields of terbium complexes with
      2,2'-bipyridine derivative ligands.
AB  - Terbium complexes are widely used as luminescent materials because of their
      bright green emission and sharp emission spectra and the independence of their
      emission wavelengths from the surrounding environment. The luminescence quantum
      yield (LQY), however, heavily depends on the surroundings, and an appropriate
      ligand design is indispensable. In this study, we focus on a Tb3+ complex
      coordinated by a 2,2'-bipyridine derivative ligand (L1), whose LQY is almost zero
      at room temperature [M. Hasegawa et al., New. J. Chem. 2014, 38, 1225] and
      compare it with a Tb3+ complex with a bipyridine ligand, which is widely used as
      a photo-antenna ligand. To discuss the LQYs of the complexes, we computed their
      energy profiles, i.e. the energetic and structural changes during the emission
      and quenching processes. The low LQY of the TbL1(NO3)2 complex was explained by
      the stability of the minimum energy crossing point between the potential energy
      surfaces of the ligand-centered lowest triplet state and the ground state, which
      was induced by the out-of-plane bending of the azomethine moiety. The most
      efficient way to improve the LQY by modification of the ligand is to replace the
      azomethine moieties by other functional groups, such as ether or reduced
      azomethine groups, whose minimum energy crossing points are unstable enough to
      reduce the rate of the quenching processes.

PMID- 29199297
TI  - Pillar[4]pyridinium: a square-shaped molecular box.
AB  - Numerous applications of Stoddart's 'blue-box', a pyridinium containing
      macrocycle of rectangular shape, encouraged us to seek successors of this amazing
      molecule. Using a one-step cyclization reaction we synthesized a square-shaped
      cyclic tetramer consisting of 4-methylenepyridinium units - pillar[4]pyridinium
      (P[4]P). Pillar[4]pyridinium is a quadruply positively charged water-soluble
      macrocycle with a highly symmetric, strained structure and an electron-deficient
      cavity. These features impel the macrocycle to assemble into channel networks in
      the solid state and render it an effective fluoride receptor in water.

PMID- 29199298
TI  - Radical halogenation-mediated latent-active glycosylations of allyl glycosides.
AB  - Radical halogenation-mediated glycosylation using allyl glycosides as donors and
      as acceptors emerges to be an efficient and hither-to unknown glycosylation
      method, adhering to the concept of the latent-active methodology. Several di- and
      trisaccharides that possess the allyl moiety at their reducing end are prepared
      through this new glycosylation methodology.

PMID- 29199299
TI  - Correction: Formic acid catalyzed isomerization of protonated cytosine: a lower
      barrier reaction for tautomer production of potential biological importance.
AB  - Correction for 'Formic acid catalyzed isomerization of protonated cytosine: a
      lower barrier reaction for tautomer production of potential biological
      importance' by Lingxia Jin et al., Phys. Chem. Chem. Phys., 2017, 19, 13515
      13523.

PMID- 29199300
TI  - Characterizing protein-protein-interaction in high-concentration monoclonal
      antibody systems with the quartz crystal microbalance.
AB  - Making use of a quartz crystal microbalance (QCM), concentrated solutions of
      therapeutic antibodies were studied with respect to their behavior under shear
      excitation with frequencies in the MHz range. At high protein concentration and
      neutral pH, viscoelastic behavior was found in the sense that the storage
      modulus, G', was nonzero. Fits of the frequency dependence of G'(omega) and
      G''(omega) (G'' being the loss modulus) using the Maxwell-model produced good
      agreement with the experimental data. The fit parameters were the relaxation
      time, tau, and the shear modulus at the inverse relaxation time, G* (at the
      "cross-over frequency" omegaC = 1/tau). The influence of two different
      pharmaceutical excipients (histidine and citrate) was studied at variable
      concentrations of the antibody and variable pH. In cases, where viscoelasticity
      was observed, G* was in the range of a few kPa, consistent with entropy-driven
      interactions. tau was small at low pH, where the antibody carries a positive
      charge. tau increased with increasing pH. The relaxation time tau was found to be
      correlated with other parameters quantifying protein-protein interactions, namely
      the steady shear viscosity (eta), the second osmotic virial coefficient as
      determined with both self-interaction chromatography (B22,SIC) and static light
      scattering (B22,SLS), and the diffusion interaction parameter as determined with
      dynamic light scattering (kD). While B22 and kD describe protein-protein
      interactions in diluted samples, the QCM can be applied to concentrated
      solutions, thereby being sensitive to higher-order protein-protein interactions.

PMID- 29199301
TI  - The cohesive energy of superheavy element copernicium determined from accurate
      relativistic coupled-cluster theory.
AB  - The cohesive energy of bulk copernicium is accurately determined using the
      incremental method within a relativistic coupled-cluster approach. For the lowest
      energy structure of hexagonal close-packed (hcp) symmetry, we obtain a cohesive
      energy of -36.3 kJ mol-1 (inclusion of uncertainties leads to a lower bound of 
      39.6 kJ mol-1), in excellent agreement with the experimentally estimated
      sublimation enthalpy of -38 kJ mol-1 [R. Eichler et al., Angew. Chem. Int. Ed.,
      2008, 47, 3262]. At the coupled-cluster singles, doubles and perturbative triples
      level of theory, we find that the hcp structure is energetically quasi-degenerate
      with both face-centred and body-centred cubic structures. These results provide a
      basis for testing various density-functionals, of which the PBEsol functional
      yields a cohesive energy of -34.1 kJ mol-1 in good agreement with our coupled
      cluster value.

PMID- 29199302
TI  - High temperature thermal management with boron nitride nanosheets.
AB  - The rapid development of high power density devices requires more efficient heat
      dissipation. Recently, two-dimensional layered materials have attracted
      significant interest due to their superior thermal conductivity, ease of
      production and chemical stability. Among them, hexagonal boron nitride (h-BN) is
      electrically insulating, making it a promising thermal management material for
      next-generation electronics. In this work, we demonstrated that an h-BN thin film
      composed of layer-by-layer laminated h-BN nanosheets can effectively enhance the
      lateral heat dissipation on the substrate. We found that by using the BN-coated
      glass instead of bare glass as the substrate, the highest operating temperature
      of a reduced graphene oxide (RGO) based device could increase from 700  degrees C
      to 1000  degrees C, and at the same input power, the operating temperature of the
      RGO device is effectively decreased. The remarkable performance improvement using
      the BN coating originates from its anisotropic thermal conductivity: a high in
      plane thermal conductivity of 14 W m-1 K-1 for spreading and a low cross-plane
      thermal conductivity of 0.4 W m-1 K-1 to avoid a hot spot right underneath the
      device. Our results provide an effective approach to improve the heat dissipation
      in integrated circuits and high power devices.

PMID- 29199304
TI  - On the underlying mechanisms of the low observed nitrate selectivity in
      photocatalytic NOx abatement and the importance of the oxygen reduction reaction.
AB  - Semiconductor photocatalysis could be an effective means to combat air pollution,
      especially nitrogen oxides, which can be mineralized to nitrate. However, the
      reaction typically shows poor selectivity, releasing a number of unwanted and
      possibly toxic intermediates such as nitrogen dioxide. Up to now, the underlying
      principles that lead to this poor selectivity were not understood so a knowledge
      based catalyst design for more selective materials was impossible. Herein, we
      present strong evidence for the slow oxygen reduction being one the causes, as
      the competing back-reduction of nitrate leads to the release of nitrogen dioxide.
      Consequently, engineering the photocatalyst for a better oxygen reduction
      efficiency should also increase the nitrate selectivity.

PMID- 29199305
TI  - A new scaling for the rotational diffusion of molecular probes in polymer
      solutions.
AB  - In the present work, we propose a new scaling form for the rotational diffusion
      coefficient of molecular probes in semi-dilute polymer solutions, based on a
      theoretical study. The mean-field theory for depletion effect and semi-empirical
      scaling equation for the macroscopic viscosity of polymer solutions are properly
      incorporated to specify the space-dependent concentration and viscosity profiles
      in the vicinity of the probe surface. Following the scheme of classical fluid
      mechanics, we numerically evaluate the shear torque exerted on the probes, which
      then allows us to further calculate the rotational diffusion coefficient Dr.
      Particular attention is given to the scaling behavior of the retardation factor
      Rrot = D/Dr with D being the diffusion coefficient in pure solvent. We find that
      Rrot has little relevance to the macroscopic viscosity of the polymer solution,
      while it can be well featured by the characteristic length scale rh/delta, i.e.
      the ratio between the hydrodynamic radius of the probe rh and the depletion
      thickness delta. Correspondingly, we obtain a novel scaling form for the
      rotational retardation factor, following Rrot = exp[a(rh/delta)b] with rather
      robust parameters of a ? 0.51 and b ? 0.56. We apply the theory to an extensive
      calculation for various probes in specific polymer solutions of poly(ethylene
      glycol) (PEG) and dextran. Our theoretical results show good agreements with the
      experimental data, and clearly demonstrate the validity of the new scaling form.
      In addition, the difference of the scaling behavior between translational and
      rotational diffusions is clarified, from which we conclude that the depletion
      effect plays a more significant role on the local rotational diffusion rather
      than the long-range translation diffusion.

PMID- 29199306
TI  - Hybrid pectin-Fe3+/polyacrylamide double network hydrogels with excellent
      strength, high stiffness, superior toughness and notch-insensitivity.
AB  - The lack of sufficient mechanical properties restricts the application of
      polysaccharide-based hydrogels in the field of biomedicine, especially load
      bearing tissue repair. Nowadays, double network (DN) hydrogels have aroused great
      interest through special cooperation between two contrasting networks. Inspired
      by this idea, here, we devised a new strategy to prepare a pectin
      Fe3+/polyacrylamide hybrid DN hydrogel using a simple two-step method. The
      introduction of Fe3+ ions into a pectin network to produce strong reversible
      ionic complexation, results in excellent toughness. Under optimal conditions, our
      hybrid DN hydrogels possessed tensile strength as high as 0.9 MPa, corresponding
      to a high strain of 1300%. Besides, our hybrid DN hydrogels also exhibited superb
      stiffness (elastic modulus ~ 1.46 MPa), toughness (fracture energy ~ 3785 J m-2),
      and water absorption capacity (85%). Loading-unloading tests showed that the
      internal fracture process of the hydrogels was continuous. Owing to the
      reversible structure of Fe3+-pectin complexation, the hybrid DN hydrogels also
      showed good fatigue resistance, notch-insensitivity and recoverability. This type
      of polysaccharide-based hydrogel has potential to broaden the application in the
      load-bearing tissue repair field.

PMID- 29199308
TI  - Frustrated packing in a granular system under geometrical confinement.
AB  - Optimal packings of uniform spheres are solved problems in two and three
      dimensions. The main difference between them is that the two-dimensional ground
      state can be easily achieved by simple dynamical processes while in three
      dimensions, this is impossible due to the difference in the local and global
      optimal packings. In this paper we show experimentally and numerically that in 2
      + epsilon dimensions, realized by a container which is in one dimension slightly
      wider than the spheres, the particles organize themselves in a triangular
      lattice, while touching either the front or rear side of the container. If these
      positions are denoted by up and down the packing problem can be mapped to a 1/2
      spin system. At first it looks frustrated with spin-glass like configurations,
      but the system has a well defined ground state built up from isosceles triangles.
      When the system is agitated, it evolves very slowly towards the potential energy
      minimum through metastable states. We show that the dynamics is local and is
      driven by the optimization of the volumes of 7-particle configurations and by the
      vertical interaction between touching spheres.

PMID- 29199309
TI  - Translational and rotational dynamics in dense suspensions of smooth and rough
      colloids.
AB  - We demonstrate that colloidal particles with surface roughness exhibit hindered
      rotational diffusion in quiescent dense suspensions. This is accomplished by the
      use of confocal microscopy and particle tracking to follow the translational and
      rotational dynamics of smooth and rough colloids suspended in a refractive index
      and density matched organic solvent. Measurement of the three-dimensional
      rotational diffusion is enabled by the addition of inert Janus tracers made of
      native colloids coated with a thin layer of aluminum. These experiments show that
      the mean square displacement (MSD) is unaffected by particle roughness, while the
      mean square angular displacement (MSAD) decreases for rough colloids at high
      volume fractions. Our results quantify the slowdown in the rotational dynamics of
      rough colloids, which is evidently due to steric frustration caused by the
      surface topography of the particles.

PMID- 29199310
TI  - Rapid, enantioselective synthesis of the C1-C13 fragment of biselyngbyolide B.
AB  - A rapid synthesis of the C1-C13 fragment of biselynbyolide A and B is reported.
      The judicious use of catalytic transformations for C-C bond formation and
      stereocenter generation greatly minimizes the use of protecting groups and
      oxidation state changes, as compared to previously reported routes to similar
      fragments.

PMID- 29199311
TI  - Centrifugation-induced fibrous orientation in fish-sourced collagen matrices.
AB  - Orientation of fibrous collagen structures plays an important role not only in
      the native function of various biological tissues but also in the development of
      next-generation tissue engineering scaffolds. However, the controlled assembly of
      collagen in vitro into an anisotropic structure, avoiding complex technical
      procedures and specialized apparatus, remains a challenge. Here, an oriented
      collagen matrix was fabricated at the macroscale by simple centrifugation, and
      the aligned topographical features of the resulting collagen matrix were revealed
      by scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      and small angle X-ray scattering. The aligned matrix exhibited a higher ultimate
      tensile strength and strain than a random matrix. Centrifugation had an impact on
      the diameter and density of the collagen fibrils, while it had no effect on their
      native D-periodicity and thermal stability. Additionally, structural anisotropy
      of the collagen matrix facilitated the proliferation and migration of NIH/3T3
      fibroblasts, compared with the random one. This simple and cost-effective method
      could lead to mass production of aligned collagen matrices and future
      possibilities for different applications in tissue engineering.

PMID- 29199312
TI  - Stereoselective synthesis of sulfonated 1-indenones via radical-triggered multi
      component cyclization of beta-alkynyl propenones.
AB  - New radical-triggered multi-component cyclizations of beta-alkynyl propenones
      have been developed, leading to 50 examples of sulfonated 1-indenones with
      generally good yields and high levels of stereoselectivity. The oxidant-free
      azosulfonylation of beta-alkynyl propenones with aryldiazonium salts and DABSO
      was realized under the neutral-redox conditions where TBHP enabled the direct
      selenosulfonylation of beta-alkynyl propenones by combining sulfinic acids and
      diphenyl diselenide. This protocol features a broad substrate scope, high
      functional group tolerance and mild reaction conditions.

PMID- 29199313
TI  - The sigma-hole revisited.
AB  - A covalently-bonded atom typically has a region of lower electronic density, a
      "sigma-hole," on the side of the atom opposite to the bond, along its extension.
      There is frequently a positive electrostatic potential associated with this
      region, through which the atom can interact attractively but noncovalently with
      negative sites. This positive potential reflects not only the lower electronic
      density of the sigma-hole but also contributions from other portions of the
      molecule. These can significantly influence both the value and also the angular
      position of the positive potential, causing it to deviate from the extension of
      the covalent bond. We have surveyed these effects, and their consequences for the
      directionalities of subsequent noncovalent intermolecular interactions, for atoms
      of Groups IV-VII. The overall trends are that larger deviations of the positive
      potential result in less linear intermolecular interactions, while smaller
      deviations lead to more linear interactions. We find that the deviations of the
      positive potentials and the nonlinearities of the noncovalent interactions tend
      to be greatest for atoms of Groups V and VI. We also present arguments supporting
      the use of the 0.001 a.u. contour of the electronic density as the molecular
      surface on which to compute the electrostatic potential.

PMID- 29199314
TI  - Raman antenna effect from exciton-phonon coupling in organic semiconducting
      nanobelts.
AB  - The highly anisotropic interactions in organic semiconductors together with the
      soft character of organic materials lead to strong coupling between nuclear
      vibrations and exciton dynamics, which potentially results in anomalous
      electrical, optical and optoelectrical properties. Here, we report on the Raman
      antenna effect from organic semiconducting nanobelts 6,13-dichloropentacene
      (DCP), resulting from the coupling of molecular excitons and intramolecular
      phonons. The highly ordered crystalline structure in DCP nanobelts enables the
      precise polarization-resolved spectroscopic measurement. The angle-dependent
      Raman spectroscopy under resonant excitation shows that all Raman modes from the
      skeletal vibrations of DCP molecule act like a nearly perfect dipole antenna
      IRaman ? cos4(theta - 90), with almost zero (maximum) Raman scattering parallel
      (perpendicular) to the nanobelt's long-axis. The Raman antenna effect in DCP
      nanobelt is originated from the coupling between molecular skeletal vibrations
      and intramolecular exciton and the confinement of intermolecular excitons. It
      dramatically enhances the Raman polarization ratio (rho = I||/I? > 25) and
      amplifies the anisotropy of the angle-dependent Raman scattering (kappaRaman =
      Imax/Imin > 12) of DCP nanobelts. These findings have crucial implications for
      fundamental understanding on the exciton-phonon coupling and its effects on the
      optical properties of organic semiconductors.

PMID- 29199315
TI  - Negishi cross-couplings in the synthesis of amino acids.
AB  - The Negishi cross-coupling is a powerful C-C bond-forming reaction widely
      utilised in many areas of organic synthesis. This review details the use of
      Negishi cross-couplings in the synthesis of unnatural amino acids. The
      application of this reaction in the preparation of aromatic, heteroaromatic, and,
      complex amino acid derivatives are reviewed and presented herein.

PMID- 29199316
TI  - Alzheimer's Association: Initiatives and Public Health Perspective.

PMID- 29199317
TI  - At a Crossroads: A Perspective on Drug Development for Alzheimer's Disease in
      2016.

PMID- 29199318
TI  - Global Alzheimer's Platform Trial Ready Cohorts for the Prevention of Alzheimer's
      Dementia.

PMID- 29199319
TI  - Effects of the Vaccine Vanutide Cridificar with QS-21 Adjuvant on Immunogenicity.

PMID- 29199320
TI  - The Paradox of Research on Dementia-Alzheimer's Disease.

PMID- 29199321
TI  - A Randomized, Double-Blind, Phase 2 Study of the Effects of the Vaccine Vanutide
      Cridificar with QS-21 Adjuvant on Immunogenicity, Safety and Amyloid Imaging in
      Patients with Mild to Moderate Alzheimer's Disease.
AB  - BACKGROUND: Vanutide Cridificar (ACC-001), a novel investigational
      immunotherapeutic vaccine designed to elicit antibodies against the N-terminal
      peptide 1-7 of the amyloid-beta peptide, believed to be important in the
      pathogenesis of Alzheimer's disease (AD). OBJECTIVES: To evaluate the
      immunogenicity, safety and impact of ACC-001 with Quillaja saponaria (QS-21)
      adjuvant on the reduction of brain fibrillar amyloid burden, assayed by positron
      emission tomography (PET) imaging, in patients with mild to moderate AD. DESIGN:
      Randomized, phase 2, interventional study. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01284387. PARTICIPANTS: Individuals with mild to moderate
      Alzheimer's disease (Mini-Mental State Examination scores 18-26; measurable
      amyloid burden in the expected range, on the screening 18F-florbetapir PET scan;
      and a Rosen modified Hachinski ischemic score <=4). INTERVENTION: Participants
      were randomized to 3 MUg or 10 MUg ACC-001 (each in combination with 50 MUg QS
      21) or placebo (without QS-21). MEASUREMENTS: Primary endpoint was the change
      from baseline to week 104 in cerebral amyloid burden as measured by the global
      cortical average (GCA) standard value uptake ratio (SUVR) based on the brain 18F
      florbetapir PET composite cortical SUVR between each ACC-001+QS-21 dose compared
      with placebo. Secondary endpoints included safety, immunogenicity and
      pharmacodynamics. Exploratory endpoints included cognitive and functional
      efficacy, and health outcome measures. RESULTS: Of 126 randomized patients
      (placebo: 40; ACC-001 3 ug+QS-21: 43; and ACC-001 10 ug+QS-21: 43), 125 received
      study treatment; 92 (73%) completed the study. Change in 18F-florbetapir PET GCA
      SUVR, was not significantly different between either of the two ACC-001+QS-21
      treatment groups and placebo (3 MUg +QS-21 vs. placebo diff=-0.03, p=0.54; 10 MUg
      +QS-21 vs. placebo diff=-0.08, p=0.07), but the trend was numerically consistent
      with a dose response. The geometric mean peak anti-Abeta IgG titers were slightly
      higher in the 10 MUg than the 3 MUg group. The proportion of responders was
      similar in both dose groups of ACC-001+QS-21. The cerebrospinal fluid (CSF) p-tau
      changes from baseline in both active treatment groups were not statistically
      different from placebo, but were numerically consistent with a dose response (3
      MUg +QS-21 vs. placebo diff=-3.2, p=0.57; 10 MUg +QS-21 vs. placebo diff=-7.0,
      p=0.19). The vMRI showed statistically significant faster treatment-related
      decrease in brain volume in the 10 MUg group but was not significant in the 3 MUg
      group, compared with placebo (3 MUg diff =-1.3 mL/year, p=0.50; 10 MUg diff=-4.2
      mL/year, p=0.02). Measured plasma Abeta levels increased in parallel with peak
      anti-Abeta titers after each injection. Amyloid-related imaging abnormalities
      with edema/effusion (ARIA-E) were more frequent in patients who received ACC
      001+QS-21 than placebo (6% vs. 0%) but none were symptomatic. The most common
      treatment-emergent adverse events in the active groups were injection reactions,
      and occurred more frequently in the ACC-001+QS-21 groups than the placebo (48% vs
      8%), the majority of which were mild and transient. CONCLUSIONS: Primary
      biomarker efficacy endpoints were not statistically significant in either dose
      group. The numerical decreases in 18F-florbetapir PET GCA SUVR suggests a dose
      related trend for greater reductions in fibrillar amyloid burden in the ACC
      001+QS-21 10 ug group compared with placebo. Likewise, while not significant,
      there was a numerical trend of decreased CSF p-tau levels with ACC-001, possibly
      consistent with a downstream effect in the ACC-001+QS-21 group. Insufficient
      antibody titers or quality, insufficient power to detect a difference, or too
      short duration of follow up may be reasons why a statistically significant
      response was not observed. Brain volume measures showed faster volume loss in the
      10 ug treatment group, similar to the effect seen in few earlier AD immunotherapy
      trials which may suggest removal of amyloid and resultant decrease in
      inflammation. No new, unexpected safety signals were detected.

PMID- 29199322
TI  - Reversible and Species-Specific Depigmentation Effects of AZD3293, a BACE
      Inhibitor for the Treatment of Alzheimer's Disease, Are Related to BACE2
      Inhibition and Confined to Epidermis and Hair.
AB  - BACKGROUND: AZD3293 (also known as LY3314814) is a novel, potent, non-selective
      BACE1/BACE2 inhibitor currently in Phase 3 clinical development for the treatment
      of Alzheimer's disease. OBJECTIVES: The purpose of these studies was to
      characterize the effects, putative mechanism, and reversibility of
      hypopigmentation following treatment with AZD3293 in pigmented Long-Evans rats,
      Beagle dogs, human cell cultures, and humans. DESIGN: Nonclinical studies were
      conducted in Long-Evans pigmented rats, and both young and older Beagle dogs
      using a variety of oral dose levels of AZD3293 or AZD3839 (BACE inhibition
      reference compound; used in older dogs only) for dosing durations of 13 to 26
      weeks. In vitro studies of normal human epidermal melanocytes and reconstituted
      human epidermis were also conducted. Skin biopsy data from a multiple-dose Phase
      1 clinical study of AZD3293 (NCT01795339) are also reported. SETTING: Nonclinical
      in vivo and in vitro studies were conducted in laboratory settings in the US,
      Canada, and France; the multiple dose clinical study was conducted in a
      specialized inpatient setting in the US. PARTICIPANTS: Beagle dogs: 13-week study
      N=36 young (8-10 mo) animals; 39-week study N=64 young animals; and a second 13
      week study N=32 older (30-32 mo) animals. Long-Evans rats: N=68 animals. Multiple
      dose clinical study: only data for subjects enrolled in Part 2 of this study are
      included in this report (N=16). INTERVENTIONS: AZD3293 was the primary
      intervention used in these studies. AZD3839, a relatively BACE1-selective
      reference inhibitor compound was used in one group in the 13 week study in older
      Beagle dogs and one in vitro assessment. Finally, AZ1340, another relatively
      BACE1-selective reference inhibitor compound was used only in one in vitro
      assessment. MEASUREMENTS: Measurements for the nonclinical studies in dogs and
      rats included macroscopic observation and assessment of skin biopsies via
      histopathology, immunochemistry, and electron microscopy. Measurements for the in
      vitro studies included melanocyte premelanosome protein (PMEL) processing,
      cytotoxicity, melanin synthesis, Pmel17 labeling, and melanocyte dendricity.
      Measurements in the clinical study included scoring of melanin content in skin
      biopsies taken before and after dosing with AZD3293 over 14 days at dose levels
      up to 150 mg. RESULTS: Depigmentation in rats and dogs was limited to skin, hair,
      and mucosa with no effects on other pigmented tissues. At a cellular level
      depigmentation was observed within a week of treatment, whereas the appearance of
      depigmentation in skin and hair did not become apparent until, at earliest, 4
      weeks of treatment. The depigmentation effects were reversible, not associated
      with degenerative or inflammatory changes, and were dose- and species-dependent
      in severity. Full recovery of melanization was observed at the microscopic
      (cellular) level and at least partial recovery was seen in the macroscopic
      appearance of animals by the end of the 12-week recovery period in both rats and
      dogs. Interestingly, no changes in melanin production or melanocyte morphology
      were seen in human primary melanocytes or reconstituted human epidermis in vitro.
      Finally, there were no changes in melanization level in skin biopsies following
      12 days of daily AZD3293 treatment at doses of AZD3293 up to 150 mg/day in human
      subjects. CONCLUSIONS: AZD3293, a novel, potent, non-selective BACE1/BACE2
      inhibitor is in development as a potentially disease-modifying treatment for
      Alzheimer's disease. Chronic nonclinical studies in Beagle dogs and pigmented
      rats showed macroscopic and microscopic hypopigmentation effects of AZD3293 that
      were limited to skin, hair, and mucosa. These effects were shown to be reversible
      in both species. Analysis of data from nonclinical and in vitro studies suggests
      that hypopigmentation is caused by BACE2 inhibition resulting in accumulation of
      a premelanosome protein fragment, which interrupts the normal production of
      melanin. No macroscopic or microscopic reports of hypopigmentation were observed
      in a Phase 1 clinical study following 13 doses of AZD3293 over 14 days at dose
      levels up to 150 mg/day. These data suggest that hypopigmentation is species
      specific and humans appear to be least sensitive to the depigmentation effect
      caused by BACE2 inhibition.

PMID- 29199323
TI  - Clinical Benefits of Tramiprosate in Alzheimer's Disease Are Associated with
      Higher Number of APOE4 Alleles: The "APOE4 Gene-Dose Effect".
AB  - BACKGROUND: Tramiprosate is an oral amyloid anti-aggregation agent that reduces
      amyloid oligomer toxicity in preclinical studies and was evaluated in two 78-week
      trials in North America and Western Europe that enrolled 2,025 patients with Mild
      to Moderate Alzheimer's Disease. The completed North American study did not
      achieve its efficacy objectives, but a pre-specified subgroup analysis suggested
      potential efficacy in apolipoprotein E4 (APOE4) carriers. To further explore this
      observation, we analyzed tramiprosate Phase 3 clinical data based on the number
      of APOE4 alleles. OBJECTIVES: To analyze tramiprosate efficacy, safety, and
      occurrence of vasogenic edema in the three APOE4 subgroups: homozygous,
      heterozygous and non-carriers. DESIGN: Randomized, double-blind, placebo
      controlled parallel-arm multi-center studies. SETTING: Academic Alzheimer's
      disease and dementia centers, community-based dementia and memory clinics, and
      neuropsychiatric clinical research sites. PARTICIPANTS: Subjects included 2,025
      patients, 50 years of age or older, with approximately 60% having APOE4 carrier
      status (10-15% homozygotes and 45-50% heterozygotes), and mild to moderate
      disease. All subjects were on stable symptomatic drugs. INTERVENTION: Randomized
      subjects received placebo, 100 mg BID, or 150 mg BID of tramiprosate.
      MEASUREMENTS: Co-primary outcomes in both studies were change from baseline in
      the ADAS-cog11 and CDR-SB assessment scales. RESULTS: Highest efficacy was
      observed in APOE4/4 homozygotes receiving 150 mg BID of tramiprosate, showing
      statistically significant effects on ADAS-cog and positive trends on CDR-SB
      (respectively, 40-66% and 25-45% benefit compared to placebo). APOE4
      heterozygotes showed intermediate efficacy, and non-carriers showed no benefit.
      In 426 patients with MRI scans, no cases of treatment-emergent vasogenic edema
      were observed. In the three subgroups, the most common adverse events were
      nausea, vomiting, and decreased weight. CONCLUSIONS: The "APOE4 Gene-Dose effect"
      is likely explained by the high prevalence of amyloid pathology in symptomatic
      APOE4 carriers. In APOE4/4 Alzheimer's disease patients, the high dose of
      tramiprosate showed favorable safety and clinically meaningful efficacy in
      addition to standard of care.

PMID- 29199324
TI  - Rationale and Structure for a New Center for Studies on Prevention of Alzheimer's
      Disease (StoP-AD).
AB  - We describe events spanning over 20 years that have shaped our approach to
      identification of interventions that may delay symptoms in Alzheimer's disease
      (AD). These events motivated the development of a new Centre for Studies on
      Prevention of AD that includes an observational cohort of cognitively normal high
      risk persons and INTREPAD, a nested two-year randomized placebo-controlled trial
      of the non-steroidal anti-inflammatory drug naproxen sodium. INTREPAD enrolled
      217 persons and will follow 160 in a modified intent-to-treat analysis of persons
      who remained on-protocol through at least one follow-up evaluation. The trial
      employs dual endpoints: 1) a composite global cognitive score generated by a
      battery of 12 psychometric tests organized into five subscales; and 2) a summary
      Alzheimer's Progression Score derived from latent variable modeling of multiple
      biomarker data from several modalities. The dual endpoints will be analyzed by
      consideration of their joint probability under the null hypothesis of no
      treatment effect, after allowing appropriately for their lack of independence. We
      suggest that such an approach can be used economically to generate preliminary
      data regarding the efficacy of potential prevention strategies, thereby
      increasing the chances of finding one or more interventions that successfully
      prevent symptoms.

PMID- 29199326
TI  - [Effect of GLUD1 on proliferation, osteogenic differentiation and mineralization
      of human dental pulp stem cells].
AB  - PURPOSE: To investigate the effect of glutamate dehydrogenase 1 (GLUD1) on
      proliferation, osteogenic differentiation and mineralization of human dental pulp
      stem cells (hDPSCs). METHODS: hDPSCs were isolated by tissue-explant method in
      vitro, and shGLUD1 lentivirus was transfected to knock down the expression of
      GLUD1. RT-PCR and Western blot were performed to detect the expression of GLUD1.
      CCK8 assay was used to evaluate cell proliferation. After culture with osteogenic
      inducing medium for 14 days, alizarin red staining was used to detect the
      formation of mineralization nodules, and RT-PCR and immunofluorescence staining
      were performed to detect the expression of Runx2 and OCN, respectively. The data
      were analyzed with SPSS 20.0 software package. RESULTS: The expression of GLUD1
      was significantly increased in hDPSCs after osteogenic induction compared with
      the control. After transfection with shGLUD1 lentivirus, GLUD1 expression was
      significantly decreased (P<0.05). Compared with the control group, mineralization
      nodule formation was significantly decreased in shGLUD1 group after osteogenic
      induction. The expression of OCN (late-staged markers for osteogenic
      differentiation) were significantly decreased both in mRNA and protein levels,
      while the expression of Runx2 (early-staged markers for osteoblast
      differentiation) was up-regulated. CONCLUSIONS: shGLUD1 inhibits the
      proliferation, mineralization and the late stage of osteogenic differentiation of
      hDPSCs in vitro. GLUD1 may play an important role in osteogenic differentiation
      of hDPSCs.

PMID- 29199325
TI  - [Effect of overexpression of transcription factor Runx2 and Osterix on osteogenic
      differentiation of endothelial cells].
AB  - PURPOSE: To explore the effect of overexpression of Runx2 and Osterix (OSX) genes
      on osteogenic differentiation of human umbilical vein endothelial cells (HUVECs).
      METHODS: Overexpressed Runx2 and OSX lentiviral vectors were transfected into
      HUVECs respectively. The osteogenic potential of transfected cells was identified
      by alkaline phosphatase (ALP) staining and ALP activity. Furthermore, real time
      PCR, Western blot and immunofluorescence staining were performed to detect the
      expression of osteogenic genes and proteins in HUVECs. GraphPad Prism 6.01
      software was used for statistical analysis. RESULTS: Overexpression of Runx2 gene
      was beneficial for osteogenic differentiation of HUVECs, while overexpression of
      osterix gene did not show osteogenic differential potential. Moreover,
      overexpression of Runx2 gene in HUVECs up-regulated the gene expression level of
      Runx2, OSX, ALP, bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin
      (OCN), and up-regulated protein level of OPN and OCN. CONCLUTIONS: Overexpression
      of Runx2 could promote osteogenic differentiation of HUVECs.

PMID- 29199327
TI  - [Construction of a lentiviral vector of RNA interference of PERK gene and
      identification in human dental pulp cells].
AB  - PURPOSE: To construct an expression vector of a small hairpin RNA (shRNA)
      targeting human PERK gene and to observe gene-silencing effects of PERK in human
      dental pulp cells (DPCs). METHODS: According to PERK gene cDNA sequence, shRNA
      was designed and synthesized, which was then annealed into hU6-MCS-CMV-EGFP
      vector. After identified by sequencing, hU6-MCS-CMV-EGFP vector and packaging
      vector were co-transfected into 293 T cells. 72 hours later, the recombinant
      lentiviruses were obtained after harvesting and concentrating. Then LV-PERK-RNAi
      vectors were transfected into DPCs at an appropriate multiplicity of infection.
      To verify the interference effect, real- time PCR and Western blot were used to
      detect expression levels of PERK mRNA and protein in the transfected DPCs. The
      data were analyzed with SPSS 24.0 software package. RESULTS: LV-PERK-RNAi vectors
      were successfully constructed with a high titer of 3*108 TU/mL. The results of RT
      PCR and Western blot demonstrated that after infection with LV-PERK-RNAi vector
      at a multiplicity of infection of 30, the expression level of PERK gene in DPCs
      was significantly down-regulated compared with control group. At mRNA level, the
      interference rate was about 63%. CONCLUSIONS: An effective lentiviral shRNA
      expression vector targeting the PERK gene is successfully constructed and can be
      used for further study on the function of PERK gene.

PMID- 29199328
TI  - [Expression of human beta-defensin and its relationship with inflammatory factor
      in human dental pulp tissue].
AB  - PURPOSE: To investigate the expression of human beta-defensin(HBD) in human
      dental pulp tissue and to explore the regulation of HBD in pulp inflammation and
      the relationship among HBD family members. METHODS: The gene expression of HBD in
      human dental pulp tissue was assessed in NCBI GEO profiles and was verified by RT
      PCR. Human dental pulp cells were stimulated with TNF-alpha, IL-1alpha, IL-1beta
      and IL-6 in different combinations and the expression of HBD2 was analyzed by
      qPCR. Human dental pulp cells were pretreated with HBD110 and then stimulated
      with LPS and the expression of TNF-alpha,IL-1alpha and HBD2 were analyzed by
      qPCR. GraphPad Prism 5.01 was used to analyze the results of the experimental and
      the control groups. RESULTS: 27 HBDs were found to express in human dental pulp
      tissue in NCBI GEO Profiles. The joint overexpression of TNF-alpha, IL-1alpha, IL
      1beta and IL-6 increased the expression of HBD2; HBD110 increased the expression
      of HBD2 by increasing the expression of TNF-alpha and IL-1alpha. CONCLUSIONS:
      Many other HBDs have positive expression in human dental pulp issue besides of
      HBD1, HBD2, HBD3, HBD4 and the inflammation factors and other HBDs can regulate
      the expression of HBD2 in dental pulp.

PMID- 29199329
TI  - [Effect of a non-thermal atmospheric pressure argon plasma jet on SOD and MDA
      levels in oral mucosal ulcer of golden hamsters].
AB  - : PURPOSE:To observe the effects of a non-thermal atmospheric pressure argon
      plasma jet on the healing time, and the levels of superoxide dismutase(SOD)and
      malondialdehyde(MDA)in oral mucosal ulcer of golden hamsters.METHODS: 56 golden
      hamsters were randomly assigned to 8 groups, one normal control group, one ulcer
      group, one natural healing group without any therapy, one iodine glycerin group,
      two argon groups (30 s, 120 s)and two plasma groups (30 s, 120 s).24 hours after
      the last treatment, 4 hamsters from each group were sacrificed to detect SOD and
      MDA levels in the oral mucosal ulcer by spectrophotometry. The healing time in
      the remaining hamsters was observed continuously for 9 days after the last
      treatment.The data were analyzed with SPSS 22.0 software package. RESULTS:The
      healing time of the plasma groups was significantly shorter than the other groups
      (P=0.00). 24 h after the last treatment, there was no significant difference
      between the plasma groups and the normal contro1 group in SOD and MDA levels
      (P>0.05), SOD level in plasma groups was significantly higher than other groups
      (P=0.00), and MDA level in plasma groups was significantly lower than other
      groups (P=0.00). There was no significant difference between 30 s and 120 s
      plasma group in SOD and MDA levels (P>0.05). CONCLUSIONS: Non-thermal atmospheric
      pressure plasma in certain dose can increase SOD level and decrease MDA level in
      ulcer tissues effectively, and reduce the healing time of oral ulcer in golden
      hamsters..

PMID- 29199330
TI  - [Effect of low-intensity pulsed ultrasound combined with triamcinolone acetonide
      on oral mucosal ulcer healing in syrian hamster].
AB  - PURPOSE: To evaluate the effect of low-intensity pulsed ultrasound(LIPUS)
      combined with triamcinolone acetonide on oral mucosal ulcer in syrian hamster in
      several ways, including healing time, contents of superoxide dismutase(SOD)and
      malondialdehyde (MDA). METHODS: Sixty syrian hamsters were randomly divided into
      5 groups, including a baseline group (containing a normal baseline group and a
      model baseline group, n=6) and 4 experimental groups (LIPUS processing and drug
      use group, LIPUS group, drug group and a normal control group without any
      processing, n=12). Four experimental groups and model baseline group were given
      oxygen free radicals to model the oral mucosal ulcer. At 24 h after the last
      treatment, the healing time of ulcer, content of SOD and MDA were compared
      between each group. SPSS 20.0 software package was used for statistical analysis.
      RESULTS: Compared with LIPUS group,drug group and control group, the healing time
      of oral mucosal ulcer in LIPUS and drug combined group was shortened. At 24 h
      after the last treatment, the activity of SOD showed that the LIPUS and drug
      combined group[(2.32+/-0.30) U/mgprot] were significantly higher than the model
      baseline group[(1.48+/-0.29) U/mgprot], the LIPUS group[(1.83+/-0.15) U/mgprot],
      the drug group[(1.76+/-0.25) U/mgprot] and control group[(1.71+/-0.18) U/mgprot]
      (P<0.05). The results of MDA content showed that the LIPUS and drug combined
      group [(8.17+/-0.21) nmol/mgprot] were significantly lower than the model
      baseline group[(9.41+/-0.22) nmol/mgprot], the LIPUS group[(9.00+/-0.44)
      nmol/mgprot], the drug group [(9.04+/-0.43) nmol/mgprot] and control
      group[(9.03+/-0.46) nmol/mgprot] (P<0.05). After oral mucosal ulcer healing, the
      activity of SOD and MDA showed that the LIPUS and drug combined group, the LIPUS
      group, the drug group and control group were not significantly different from the
      normal baseline group (P>0.05). CONCLUSIONS: Low-intensity pulsed ultrasound
      combined with triamcinolone acetonide can effectively improve the activity of SOD
      and reduce the contents of MDA in ulcerated tissues, and therefore accelerate the
      process of ulcer healing..

PMID- 29199331
TI  - [Expression of SOCS-1 and SOCS-3 in chronic periapical lesions and its clinical
      significance].
AB  - PURPOSE: To detect the expression of suppressor of cytokine signaling-1 (SOCS-1)
      and suppressor of cytokine signaling-3 (SOCS-3) in chronic periapical lesions and
      to clarify their roles in pathogenesis of apical periodontitis. METHODS: A total
      of 25 chronic periapical lesion tissues and 16 normal periodontal ligament
      tissues were collected respectively. The expression of mRNA was measured by real
      time PCR, the protein expression was measured by immunohistochemical analysis.
      Statistical analysis was performed using SPSS 13.0 software package. RESULTS:
      Immunohistochemical results indicated that expression levels of SOCS-1 and SOCS-3
      protein in chronic periapical lesions were significantly higher than that in
      normal tissues (P<0.01); Moreover, SOCS-1 and SOCS-3 protein expression levels in
      severe inflammation group were significantly higher than that in mild
      inflammation group (P<0.01). In mild inflammation group, severe inflammation
      group and control group, the expression levels of SOCS-1 mRNA were 2.620+/-1.552,
      2.373+/-1.083 and 1.277+/-1.040, whereas those of SOCS-3 were 9.308+/-5.901,
      7.565+/-3.233 and 1.232+/-1.099, respectively. CONCLUSIONS: The expression levels
      of SOCS-1 mRNA and SOCS-3 mRNA are significantly higher both in mild inflammation
      group and severe inflammation group than that in control group (P<0.01), while no
      significant difference is found in mild and severe inflammation group.

PMID- 29199332
TI  - [Effect of HBXIP on biological function and PI3K/Akt signaling pathway of adenoid
      cystic carcinoma cell line ACC-M].
AB  - PURPOSE: To study the effect of hepatitis B virus X protein binding protein
      (HBXIP) on proliferation, migration and invasion of adenoid cystic carcinoma cell
      line ACC-M, and the possible mechanism of PI3K/Akt signaling pathway. METHODS:
      HBXIP plasmid was transfected into ACC-M. The cells were divided into
      experimental group (transfected with plasmid pEGFP-N1-HBXIP) control group (non
      transfected group) and blank control group (vector group, pEGFP-N1). RT-PCR was
      used to detect the expression HBXIP in ACC-M; MTT assay, transwell chamber
      experiments and scratches over the proliferation of HBXIP were utilized
      individually to evaluate the influence of HBXIP on ACC-M expression, migration
      and invasion; Western blotting was used to detect the protein expression of Akt,
      p-Akt, PI3K, p-PI3K and S100A4 after overexpression of HBXIP. Statistical
      analysis was performed using SPSS 18.0 software package. RESULTS: MTT results
      showed that the number of surviving cells of experimental group was significantly
      higher than the control group (P<0.05); Scratch test results showed that the cell
      mobility of the experimental group was significantly higher than the control
      group (P<0.01); Transwell chamber experiments showed that the number of cell
      invasion of the experimental group was significantly higher than the control
      group (P<0.01); Western blotting results showed that compared with the control
      group, the expression of p-Akt, p-PI3K and S100A4 in the experimental group with
      overexpressed HBXIP was relatively increased. CONCLUSIONS: Overexpression of
      HBXIP gene promotes ACC-M proliferation, invasion and migration. Further, ACC-M
      proliferation, invasion and migration may be promoted by increased Akt, PI3K
      phosphorylation and S100A4 protein expression.

PMID- 29199333
TI  - [Study on the sealing ability of biological root canal sealer iRoot SP in root
      canal filling].
AB  - PURPOSE: To investigate the sealing ability of biological root canal sealer iRoot
      SP in over-root canal filling. METHODS:After completion of root canal
      preparation, 48 extracted human single-canal teeth were used. The ratio of mesio
      distal root canal diameter to bucco-lingual diameter was less than 0.5. The teeth
      were randomly divided into group A, B and C. The root canals were obturated with
      root canal filling agent (group A), AH Plus (group B) and iRoot SP (group C),
      respectively; the apical leakage was evaluated by dye penetration method and
      transparent teeth technique. The data were analyzed using SPSS 19.0 software
      package. RESULTS: The depth of dye penetration in group A was significantly
      higher than that in group B and C (P<0.05); there was no significant difference
      in the depth of dye penetration between group B and group C (P>0.05).
      CONCLUSIONS: The apical sealing ability of iRoot SP is equivalent to AH Plus in
      oval-root canal, both are better than that of root canal filling agent..

PMID- 29199334
TI  - [Effect of transfected EphB4 on osteogenic differentiation in stem cells from
      human exfoliated deciduous teeth].
AB  - PURPOSE: To evaluate the effect of stem cells from human exfoliated deciduous
      teeth (SHED) transfected with EphB4 gene in regulating osteogenic
      differentiation. METHODS: Human dental pulp tissue were harvested from extracted
      deciduous teeth and digested by collagenase and dispase. The SHEDs were
      transfected with transgenic (hEphB4-GFP) vector or empty vector (GFP-vector).
      Real time-polymerase chain reaction(real time-PCR) analysis and Western blot were
      used to detect the expression of EphB4 in SHEDs after transfection. EphB4-SHEDs
      and GFP-SHEDs were subjected to osteogenic induction and assessed by alkaline
      phosphatase(ALP) assay and Alizarin-red S staining. SPSS 16.0 software package
      was used for statistical analysis. RESULTS: Real time-PCR revealed that the
      expression of EphB4 was significantly enhanced in EphB4-SHEDs compared to GFP
      SHEDs (P<0.05). The expression of EphB4 protein was significantly higher (P<0.05)
      in EphB4-SHEDs compared to GFP-SHEDs. ALP assay and Alizarin-red S staining
      demonstrated higher ALP activity and increased mineralization with EphB4-SHEDs.
      CONCLUSIONS: The results indicate that transgenic expression of EphB4 in SHEDs
      could promote osteogenic differentiation.

PMID- 29199335
TI  - [Effect of flowablenano-composite on the bonding strength of tooth reattachment
      on fractured crowns].
AB  - PURPOSE: To study the effect of flowable nano-composite and different resin
      adhesives on reattachment of fractured crowns. METHODS: Thirty four fractured
      human maxillary incisors were obtained and randomly assigned into 4 groups and
      reattached using two types of adhesives: Easy one (EO) and Single bond 2(SB2),
      with or without Filtek Z350 flowable nano-composite. Four days after reattaching,
      the teeth were tested to achieve the shear bonding strength (SBS) and the
      recovery rate of fracture resistance after reattachment (R) were calculated.
      Statistical analysis was performed by use of SPSS 20.0 software package. RESULTS:
      Using flowable nano-composite failed to increase the SBS and R.The recovery rates
      of the specimens using EO without flowable composite achieved the highest value
      and they were significantly higher than those of the specimens using SB2 without
      flowable composite (P=0.046). CONCLUSIONS: If the fragment matches the fractured
      tooth perfectly, the tooth reattached using EO without composite will achieve
      higher bonding strength. However, not all the adhesives can be used to reattach
      without composite. Clinical decisions should be made on two aspects: whether the
      selected adhesive has sufficient mechanical strength and if there is any loss of
      tooth tissue after fracture.

PMID- 29199336
TI  - [Significance of Smad4, Smad7 and Caveolin-1 expression in oral mucosa
      carcinogenesis of Wistar rats].
AB  - PURPOSE: To investigate the expression of Smad4, Smad7 and Caveolin-1 in the
      process of carcinogenesis of oral mucosa in Wistar rats, and to understand the
      changes of TGF-beta/Smad signaling pathway and Caveolin-1 in oral cancer.
      METHODS: Palatal mucosal carcinogenesis specimens of Wistar rats were obtained
      from School of Stomatology, Zhengzhou University, which included 5 samples of
      normal mucosa, 10 samples of simple hyperplasia mucosa, 6 samples of mild mucosal
      dysplasia, 7 samples of moderate mucosal dysplasia, 13 samples of mucosa severe
      mucosal dysplasia, and 28 samples of oral cancer tissue. The expression of Smad4,
      Smad7 and Caveolin-1 was detected by immunohistochemistry. SPSS15.0 software
      package was used for statistical analysis. RESULTS: The expression of Smad4
      decreased in normal and hyperplastic epithelia, dysplasticepithelia and oral
      cancer gradually, the difference of the expression among the three groups was
      significant (P<0.05). The expression of Smad7 and Caveolin-1 increased in normal
      and hyperplastic epithelia, dysplasticepithelia and oral cancer gradually,
      respectively; the difference of the expression among the 3 groups was significant
      (P<0.05). Spearman correlation analysis showed that Smad4 was negatively
      correlated with Smad7, Smad4 was negatively correlated with caveolin-1, Smad7 was
      positively correlated with Caveolin-1 (P<0.05). CONCLUSIONS: Synergistic effects
      may exist among Smad4, Smad7 and caveolin-1 in carcinogenesis of oral cancer.

PMID- 29199337
TI  - [Evaluation of profile aesthetics of skeletal Class II patients with different
      treatment methods].
AB  - PURPOSE: To study the aesthetic appearance of skeletal Class II patients with
      maxillary protrusion and mandibular retrusion treated with different methods.
      METHODS: The facial profile photographs and lateral cephalometric radiographs of
      a Chinese woman suffering from skeletal Class II with maxillary protrusion and
      mandibular retrusion was digitized.The digital images were modified to obtain
      orthodontic compensatory treatment, genioplasty with different advancement ranges
      and orthognathic treatment comprising 6 profiles by Photoshop
      software,orthodontic professionals and non-professionals were chosen to score the
      pictures. Post hoc tests were done with ANONA and the Student Keuls method to
      analyze the data Using SPSS22.0 software package. RESULTS: The profile with the
      highest score was the picture treated by orthognathic and orthodontic treatment.
      The profile with genioplasty (advancement of 4 mm) took the second place. When
      the advancement distance of genioplasty was 8 mm, the score was under the score
      of orthodontic compensatory treatment profile. CONCLUSIONS: Orthognathic
      orthodontic treatment of skeletal Class II is still the best treatment option to
      improve facial aesthetics. Genioplasty, as a adjuvant treatment, improves the
      appearance based on compensatory orthodontic treatment to some extent, but not
      comparable to orthognathic-orthodontic treatment.

PMID- 29199338
TI  - [A clinical analysis of screw-retained implant-supported casted integrated
      abutment crowns in the molar region with limited interocclusal space].
AB  - PURPOSE: To observe the clinical effects of screw-retained implant-supported
      casted abutment integrated crowns (IACs) in the molar region with limited
      interocclusal space. METHODS: This study involved 507 implants in 376 patients
      with limited interocclusal space in the molar region. All implants were inserted
      to the jaw by standard one-stage protocol. Screw-retained IACs were used as the
      final prosthesis. With 6 to 24 months follow-up, the clinical effects of screw
      retained IACs were recorded and analyzed using SPSS 17.0 software package.
      RESULTS: During 6 to 24 months of follow-up, the implant survival rate was
      99.61%. 37 patients had ceramic fracture which mainly happened in the group with
      3-4 mm interocclusal space. In each group, porcelain fused to metal (PFM)
      prosthesis had ceramic fracture more easily than PFM prosthesis without porcelain
      on occlusal surface(P<0.05). As the interocclusal space became smaller, the
      probability of collapsing porcelain increased(P<0.05).13 patients had screw
      loosening. 13 patients suffered from gingival swelling and bleeding, they were
      given periodontal treatment and oral hygiene instruction. Patients were satisfied
      with the restoration results. CONCLUSIONS: Screw-retained IACs can be used to
      repair missing teeth in the molar region with limited interocclusal space.

PMID- 29199339
TI  - [Assessment of pulpotomy in cariously exposed permanent teeth].
AB  - PURPOSE: To observe the clinical effect of pulpotomy for cariously exposed
      permanent teeth with closed apices and provide guidance for clinical application.
      METHODS: Sixty-two cariously exposed permanent teeth with closed apices and vital
      pulps were included. Preoperative pulpal and periapical diagnosis was
      established. The teeth were divided into two groups, the experimental group was
      treated with pulpotomy(32 cases), and the control group was treated with one
      visit root canal therapy (one-visit RCT) (30 cases). Clinical and radiographic
      evaluation was completed at 1 month, 3 months, 6 months, 12 months
      postoperatively. Statistical analysis was performed using SPSS 18.0 software
      package. RESULTS: After 1 year, the success rate of pulpotomy was 93.75%, and the
      success rate of root canal therapy was 93.10%. There was no significant
      difference between pulpotomy and root canal therapy(P=0.665). CONCLUSIONS: The
      advantages of pulpotomy are less invasive and less tooth destruction. It is a
      successful treatment option for cariously exposed pulps in mature permanent
      teeth.

PMID- 29199340
TI  - [Analysis of relative factors associated with postoperative infection of
      mandibular fractures].
AB  - PURPOSE: To explore risk factors associated with postoperative inflammatory
      complications(POIC) after rigid internal fixation of mandibular fractures.
      METHODS: A case-control study was designed and a sample of 447 patients treated
      with rigid internal fixation for mandibular fractures were selected from January
      2009 to December 2015.26 patients developed POIC after treatment were categorized
      into the experimental group. Twenty-six cases with no complications were enrolled
      into the control group. Data were collected and bivariate and multiple logistic
      analyses were used to identify factors associated with POIC between the two
      groups by SAS9.2 software package. RESULTS: In multiple regression model, an
      increasing Mandibular Injury Severity Score (OR=2.509; 95%CI 1.083-5.814) and
      health condition below the baseline (OR=5.019; 95%CI 1.294-19.472) were
      significantly (P<0.05) associated with an increased risk for a POIC. However, in
      bivariate analyses, the use of antibiotics was associated with POIC (P<0.05).
      CONCLUSIONS: Postoperative inflammatory complications are associated with the
      Mandibular Injury Severity and health condition of the patients.

PMID- 29199341
TI  - [Expression of receptor activator of nuclear factor-kappaB ligand in keratocystic
      odontogenic tumor before and after decompression].
AB  - PURPOSE: To investigate the expression of receptor activator of nuclear factor
      kappaB ligand (RANKL) in keratocystic odontogenic tumor (KCOT) before and after
      decompression. METHODS: Twenty two pairs of paraffin-embeded tissue specimens of
      KCOT were collected and subjected to immunohistochemical analysis of RANKL.The
      data were analyzed with SPSS17.0 software package for paired t test. RESULTS:
      RANKL positive cells were observed in the preoperative KCOT epithelium. The
      expression of RANKL was down-regulated after decompression(P<0.05). CONCLUSIONS:
      Decrease of RANKL expression after decompression may facilitate the lining
      epithelium of KCOT transforming to normal oral mucosal epithelium.

PMID- 29199342
TI  - [Survey of periodontal health in medical college students after 3 years of
      periodontal health maintenance].
AB  - PURPOSE: To observe and evaluate the status of periodontal disease in young
      people and the effect of intervention to control the development of periodontal
      diseases. METHODS: One hundred and fifty-three medical college students were
      randomly divided into group A (receiving interventions) and group B (no
      interventions). They were followed up for 3 years. The subjects in group A
      received oral health education, including selection of the toothbrush, the right
      way to brush teeth, the use of dental floss and interdental brush. At the same
      time ,they were given initial periodontal treatment according to the actual
      situation, and received oral health education, periodontal maintenance treatment,
      and reinforced plaque control every six months. The changes of debris index (DI),
      calculus index (CI), probing depth (PD), clinical attachment loss (CAL), bleeding
      on probing (BOP) and gingival index (GI) before and after interventions were
      compared. Statistical analysis was performed using SAS 6.12 software package.
      RESULTS: Three years later, CI and DI in group A declined significantly compared
      to the baseline (P<0.01), but there was no significant changes in group B
      (P>0.05). There was significant difference in the changes of PD, BOP and GI
      between group A and B (P<0.01). Significant difference of the change of CAL
      between group A and B was also found(P<0.05), CAL in group B was significantly
      higher than that in group A. CONCLUSIONS: There are positive effects of regular
      periodontal health maintenance and oral health education on periodontal health.

PMID- 29199343
TI  - [Diagnostic value of diffusion-weighted magnetic resonance imaging for solid
      tumors affecting the base of tongue and glossopharynx].
AB  - PURPOSE: The objective of the present study was to evaluate the potential
      application value of diffusion-weighted magnetic resonance imaging (DW-MRI) to
      differentiate solid benign from malignant tumors affecting the base of tongue and
      glossopharynx. METHODS: Sixty-one patients who presented with solid tumors
      affecting the base of tongue and glossopharynx underwent conventional MRI and DW
      MRI before pathologic verification. Based on pathologic findings, the tumors were
      classified into 4 groups: Group 1, solid benign tumor (n=10); Group 2, epithelial
      carcinoma (n=35); Group 3: non- epithelial malignant tumor (n=16); and Group 4:
      malignant tumor (n=51, a combination of Group 2 and 3). The mean apparent
      diffusion coefficients (ADCs) were computed from DW-MRI scans obtained with b
      factors of 0 and 1000 s/mm2. SAS 9.1 software package was used for Wilcoxon test.
      RESULTS: The mean ADCs were significantly different (P<0.05) between group 1 and
      the other 3 groups, and between group 2 and group 3, respectively. Among all
      kinds of pathological types of lesions, non-Hodgkin lymphoma had a lowest mean
      ADC value, and schwannoma had a highest mean ADC value. In addition, the mean
      ADCs among epithelial carcinoma subtypes were not significantly
      different(P>0.05). CONCLUSIONS: DW-MRI has differential diagnostic value of solid
      tumors affecting the base of tongue and glossopharynx, especially in
      distinguishing between benign solid tumors and malignant tumors, and between
      epithelial carcinomas and non-epithelial malignant tumors.

PMID- 29199344
TI  - [Eight-year clinical results of SLA surface implant for dentition defect].
AB  - PURPOSE: To evaluate the clinical effect of titanium implants with SLA surface
      preparation for partial prostheses. METHODS: One hundred and ninety-one implants
      with SLA surface preparation were implanted in 130 patients with dentition defect
      who required dental repair at Yantai Stomatologic Hospital Implant Center.
      Successful rate of the implant, changes of soft and hard tissue around the
      implants as well as the stability of the superstructure were recorded and
      evaluated by regular clinical and X-ray examinations. Data analysis was performed
      using SPSS 17.0 software package. RESULTS: Twenty four patients with 31 implants
      were lost to follow up, one implant which loosened 1 week after operation was
      extracted. Four implants were found with peri-implantitis. The dropout rate,
      survival rate and successful rate was 18.46%, 99.38% and 96.88%, respectively. No
      obvious biological complications were observed in 155 successful implants during
      the observation period. Eight years later, the marginal bone resorption reached
      to (1.34+/-0.52) mm. After 8 years, a total of 25 implants had mechanical
      complications, including superstructure screw mobility, falling off of the crown,
      porcelain fracture of restorations, implant fracture and the prosthesis success
      rate was 83.87%. CONCLUSIONS: SLA surface implant can not only achieve good bone
      integration, but also long-time maintainanance of the soft tissue around the
      implant and implant superstructure at a healthy and stable state,the clinical
      effect is better than other dental implants.

PMID- 29199345
TI  - [Clinical application of individualized three-dimensional printing implant
      template in multi-tooth dental implantation].
AB  - PURPOSE: To study the value and satisfaction of three-dimensional printing
      implant template and conventional implant template in multi-tooth dental
      implantation. METHODS: Thirty cases (83 teeth) with missing teeth needing to be
      implanted were randomly divided into conventional implant template group (CIT
      group, 15 cases, 42 teeth) and 3D printing implant template group (TDPIT group,
      15 cases, 41 teeth). Patients in CIT group were operated by using conventional
      implant template, while patients in TDPIT group were operated by using three
      dimensional printing implant template. The differences of implant neck and tip
      deviation, implant angle deviation and angle satisfaction between the two groups
      were compared. The difference of probing depth and bone resorption of implant
      were compared 1 year after operation between the two groups. The difference of
      success rate and satisfaction of dental implantation were compared 1 year after
      operation between the two groups. SPSS19.0 software package was used for
      statistical analysis. RESULTS: The deviation direction of the neck and the tip in
      disto-mesial, bucco-palatal, vertical direction and angle of implants in disto
      mesial and bucco-palatal direction in TDPIT group were significantly lower than
      in CIT group (P<0.05), and angle satisfaction of implants in disto-mesial and
      bucco-palatal direction in TDPIT group were significantly higher than in CIT
      group (P<0.05). There was no significant difference between the two groups in the
      probing depth and bone resorption of implants 1 year after operation (P>0.05).
      The difference of the cumulative success rate in dental implantation at 3 months
      and 6 months between the two groups were not significant (P>0.05), but the
      cumulative success rate of TDPIT group was significantly higher than CIT group at
      9 months and 1 year (90.48% vs 100%,P=0.043). The patients' satisfaction rate of
      dental implantation in TDPIT group was significantly higher than in CIT group
      (86.67% vs 53.33%, P=0.046). CONCLUSIONS: Using three-dimensional printing
      implant template can obtain better accuracy of implant, higher implant success
      rate and better patients' satisfaction than using conventional implant template.
      It is suitable for clinical application.

PMID- 29199346
TI  - [Study of angle between maxillary incisor and alveolar bone using cone-beam CT].
AB  - PURPOSE: To measure the angle between maxillary incisor and alveolar bone by the
      use of cone-beam CT (CBCT), in order to assess preoperative risks and provide
      guidance in anterior dental implantation. METHODS: A total of 374 patients were
      included and divided into 3 age groups: group 1 (18-34 years), group 2 (35-59
      years) and group 3(above 60 years). All patients underwent CBCT preoperatively,
      the angle between maxillary incisor and alveolar bone was measured though Kavo
      eXam Vision software. The data were analyzed with SPSS16.0 software package for
      Student's t test. RESULTS: In group 1, 2 and 3, the angle between maxillary
      incisor and alveolar bone was (13.81+/-4.37) degrees , In group 2, the ankle
      between maxillary incisor and alveolar bone was (15.19+/-5.23) degrees , (18.51+/
      6.62) degrees , respectively; there was no significant difference between male
      and female in each group, but there was significant difference between every 2
      age groups in the angle between maxillary incisor and alveolar bone. CONCLUSIONS:
      The angle between maxillary incisor and alveolar bone is increasing with the
      increase of age, but no significant difference between male and female is
      detected. For patients with dental implantation in anterior area, CBCT should be
      taken to measure the angle between maxillary incisor and alveolar bone for
      aesthetic assessment, especially for old patients.

PMID- 29199347
TI  - [Analysis of factors affecting soft tissue infection after oral and maxillofacial
      debridement].
AB  - PURPOSE: To explore the factors affecting soft tissue infection after oral and
      maxillofacial debridement. METHODS: Fifty hundred patients with debridement were
      enrolled in this study from January 2013 to June 2016. The patients were divided
      into 2 groups according to soft tissue infection, 18 cases in infection group and
      482 cases in non-infection group. Age, mean time to surgery, average length of
      stay, duration of antibiotics use, abbreviated injury scale (AIS), combined
      injuries, maxillofacial fractures, soft tissue injury, type of fracture, and
      history of diabetes were recorded and analyzed using SPSS 19.0 software package.
      RESULTS: The factors influencing soft tissue infection after oral and
      maxillofacial surgery were the aged, longer hospital stay, longer operation time,
      longer antibiotics use time, higher AIS score, Jaw bone injury and diabetes.
      CONCLUSIONS: The factors influencing soft tissue infection after oral and
      maxillofacial debridement are various. The aged, longer operation time, higher
      AIS score, jaw bone involvement lip and chin injury as well as diabetes might be
      the independent factors. Health care providers should give preventive measures to
      reduce the incidence of infection, according to specific factors.

PMID- 29199348
TI  - Unhealthy lifestyle and sleep problems as risk factors for increased direct
      employers' cost of short-term sickness absence.
AB  - Objectives Unhealthy lifestyle (eg, smoking) as well as sleep problems are
      associated with increased risk of sickness absence, but the financial impact of
      these associations beyond risk ratios is not well known. We aimed to estimate the
      additive contribution of lifestyle and sleep problems (risk factors) to direct
      costs of short-term (<15 days) sickness absence. Methods The Helsinki Health
      Study is a longitudinal cohort of employees of the City of Helsinki, Finland
      (N=8960, response rate 67%). During 2000-2002 the participants were mailed a
      survey questionnaire that gathered information on their lifestyle and sleep. A
      sum of the risk factors was calculated: participants received one point for being
      a smoker; high alcohol user (>7 servings/week for women and >14 servings/week for
      men); physically inactive [<14 metabolic equivalents (MET) hours/week]; having
      low fruit and vegetable consumption (<1 times/day); or suffering from frequent
      insomnia symptoms. Sickness absence, salary, and time of employment were followed
      through the employer's register between 2002-2016. Individual salary data were
      used to calculate the direct costs of short-term sickness absence. Data were
      analyzed using a two-part model. Results Direct costs of short-term sickness
      absences were on average ?9057 (standard deviation ?11 858) per employee over the
      follow-up. Those with >=3 risk factors had ?3266 [95% confidence interval (95%
      CI) ?2114-4417] higher direct costs for the employer over the follow-up compared
      to those without any risk factors. Conclusions Unhealthy lifestyle and sleep
      problems may increase the costs of short-term sickness absence to the employer by
      10-30%. Consequently, programs addressing lifestyle and sleep may yield to
      significant savings.

PMID- 29199349
TI  - Methotrexate Management in Psoriasis: Are We Following the Guidelines?

PMID- 29199350
TI  - A Rapidly Expanding Ulcer in the Armpit of a 48-year-old Man: A Quiz.

PMID- 29199351
TI  - Significant Changes in the Skin Microbiome in Patients with Chronic Plaque
      Psoriasis after Treatment with Narrowband Ultraviolet B.
AB  - Changes in the skin microbiome have been shown to promote cutaneous inflammation.
      The skin microbiome of patients with chronic plaque type psoriasis was analysed
      before and after treatment with narrowband ultraviolet B (UVB). Swab samples of
      the microbiome were taken from lesional and non-lesional skin of 26 patients.
      Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the
      Illumina MiSeq platform. Lesional skin microbiome diversity correlated with
      psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI).
      There was a significantly lower abundance of the phylum Firmicutes and the genus
      Staphylococcus in lesional skin compared with non-lesional skin before UVB
      treatment. Responders (> 75% target Psoriasis Severity Index (PSI) improvement)
      had significantly lower abundance of the phyla Firmicutes in lesional and non
      lesional skin and lower abundance of the genera Staphylococcus, Finegoldia,
      Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional
      skin after UVB treatment. Pseudomonas significantly decreased in lesional and non
      lesional skin of treatment responders. These results suggest that skin microbiome
      alterations after UVB treatment could be related to treatment and treatment
      response.

PMID- 29199353
TI  - Identification and characterization of six glycosyltransferases involved in the
      biosynthesis of a new bacterial exopolysaccharide in Paenibacillus elgii.
AB  - Paenibacillus elgii B69 produces a new xylose-containing exopolysaccharide (EPS)
      that effectively removes the pollutants from wastewater through flocculation.
      However, information about the biosynthesis of this EPS is limited. In this
      study, sequence analysis showed six putative glycosyltransferases (GTs) genes in
      polysaccharide gene clusters involved in glycosidic linkages of repeating units.
      Each gene was deleted and phenotypes were examined to understand the functions of
      these genes. Two of the genes were deleted successfully to encode a priming
      glucose GT and a side-chain xylose GT, but other genes were unsuccessfully
      deleted because of the accumulation of toxic intermediate products. The six genes
      were cloned and expressed in Escherichia coli, and the corresponding enzymes were
      purified. The activity of GTs was analyzed through mass spectrometry by using the
      purified membrane fraction as a lipid carrier receptor after a hexasaccharide
      repeated unit was reconstructed in vitro. The specificities of six different GTs
      and the building order of the hexasaccharide were characterized. This study
      provided a basis for future research on the biosynthetic pathway of EPS in
      Paenibacillus or other genera.

PMID- 29199352
TI  - An aptamer-based biosensor for detection of doxorubicin by electrochemical
      impedance spectroscopy.
AB  - An aptamer-based biosensor was developed for the detection of doxorubicin using
      electrochemical impedance spectroscopy. Doxorubicin and its 14-dehydroxylated
      version daunorubicin are anthracyclines often used in cancer treatment. Due to
      their mutagenic and cardiotoxic effects, detection in groundwater is desirable.
      We developed a biosensor using the daunorubicin-binding aptamer as biological
      recognition element. The aptamer was successfully co-immobilized with
      mercaptohexanol on gold and a density of 1.3*1013 +/- 2.4*1012 aptamer molecules
      per cm2 was achieved. The binding of doxorubicin to the immobilized aptamer was
      detected by electrochemical impedance spectroscopy. The principle is based on the
      inhibition of electron transfer between electrode and ferro-/ferricyanide in
      solution caused by the binding of doxorubicin to the immobilized aptamer. A
      linear relationship between the charge transfer resistance (R ct ) and the
      doxorubicin concentration was obtained over the range of 31 nM to 125 nM
      doxorubicin, with an apparent binding constant of 64 nM and a detection limit of
      28 nM. With the advantages of high sensitivity, selectivity, and simple sensor
      construction, this method shows a high potential of impedimetric aptasensors in
      environmental monitoring. Graphical abstract Measurement chamber and
      immobilization principle for the detection of doxorubicin by electrochemical
      impedance spectroscopy.

PMID- 29199354
TI  - Enhanced bacterial cellulose production by Gluconacetobacter xylinus via
      expression of Vitreoscilla hemoglobin and oxygen tension regulation.
AB  - Oxygen plays a key role during bacterial cellulose (BC) biosynthesis by
      Gluconacetobacter xylinus. In this study, the Vitreoscilla hemoglobin (VHb)
      encoding gene vgb, which has been widely applied to improve cell survival during
      hypoxia, was heterologously expressed in G. xylinus via the pBla-VHb-122 plasmid.
      G. xylinus and G. xylinus-vgb + were statically cultured under hypoxic (10 and
      15% oxygen tension in the gaseous phase), atmospheric (21%), and oxygen-enriched
      conditions (40 and 80%) to investigate the effect of oxygen on cell growth and BC
      production. Irrespective of vgb expression, we found that cell density increased
      with oxygen tension (10-80%) during the exponential growth phase but plateaued to
      the same value in the stationary phase. In contrast, BC production was found to
      significantly increase at lower oxygen tensions. In addition, we found that BC
      production at oxygen tensions of 10 and 15% was 26.5 and 58.6% higher,
      respectively, in G. xylinus-vgb + than that in G. xylinus. The maximum BC yield
      and glucose conversion rate, of 4.3 g/L and 184.7 mg/g, respectively, were
      observed in G. xylinus-vgb + at an oxygen tension of 15%. Finally, BC
      characterization suggested that hypoxic conditions enhance BC's mass density,
      Young's modulus, and thermostability, with G. xylinus-vgb + synthesizing softer
      BC than G. xylinus under hypoxia as a result of a decreased Young's modulus.
      These results will facilitate the use of static culture for the production of BC.

PMID- 29199355
TI  - Assessment of MODIS-derived indices (2001-2013) to drought across Taiwan's
      forests.
AB  - Tropical and subtropical ecosystems, the largest terrestrial carbon pools, are
      very susceptible to the variability of seasonal precipitation. However, the
      assessment of drought conditions in these regions is often overlooked due to the
      preconceived notion of the presence of high humidity. Drought indices derived
      from remotely sensed imagery have been commonly used for large-scale monitoring,
      but feasibility of drought assessment may vary across regions due to climate
      regimes and local biophysical conditions. Therefore, this study aims to evaluate
      the feasibility of 11 commonly used MODIS-derived vegetation/drought index in the
      forest regions of Taiwan through comparison with the station-based standardized
      precipitation index with a 3-month time scale (SPI3). The drought indices were
      further transformed (standardized anomaly, SA) to make them better delineate the
      spatiotemporal variations of drought conditions. The results showed that the
      Normalized Difference Infrared Index utilizing the near-infrared and shortwave
      infrared bands (NDII6) may be more superior to other indices in delineating
      drought patterns. Overall, the NDII6 SA-SPI3 pair yielded the highest correlation
      (mean r +/- standard deviation = 0.31 +/- 0.13) and was most significant in
      central and south Taiwan (r = 0.50-0.90) during the cold, dry season (January and
      April). This study illustrated that the NDII6 is suitable to delineate drought
      conditions in a relatively humid region. The results suggested the better
      performance of the NDII6 SA-SPI3 across the high climate gradient, especially in
      the regions with dramatic interannual amplifications of rainfall. This synthesis
      was conducted across a wide bioclimatic gradient, and the findings could be
      further generalized to a much broader geographical extent.

PMID- 29199356
TI  - Primary effusion lymphoma-like lymphoma with a T cell phenotype.

PMID- 29199357
TI  - Further classification of neutrophil non-muscle myosin heavy chain-IIA
      localization for efficient genetic diagnosis of MYH9 disorders.

PMID- 29199358
TI  - Enhancement of a visual reinforcer by D-amphetamine and nicotine in adult rats:
      relation to habituation and food restriction.
AB  - RATIONALE AND OBJECTIVES: Nicotine and D-amphetamine can strengthen reinforcing
      effects of unconditioned visual stimuli. We investigated whether these
      reinforcement-enhancing effects reflect a slowing of stimulus habituation and
      depend on food restriction. METHODS: Adult male rats pressed an active lever to
      illuminate a cue light during daily 60-min sessions. Depending on the experiment,
      rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg
      IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman
      (0.03-10 MUg/kg IV). Experiment 1 tested for possible reinforcement-enhancing
      effects of D-amphetamine and norharman. Experiment 2 investigated whether
      nicotine and amphetamine inhibited the spontaneous within-session decline in
      lever pressing. Experiment 3 assessed the effects of food restriction. RESULTS:
      Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever
      pressing specifically (two- to threefold increase). The highest doses of nicotine
      and amphetamine also affected inactive lever responding (increase and decrease,
      respectively). With the visual reinforcer omitted, responding was largely
      extinguished. Neither drug appeared to slow habituation, as assessed by the
      within-session decline in lever pressing, and reinforcement-enhancing effects
      still occurred if the drugs were given after this decline had occurred. Food
      restriction enhanced the reinforcement-enhancing effect of amphetamine but not
      that of nicotine. CONCLUSIONS: Responding remained goal-directed after several
      weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement
      enhancement even in free-feeding subjects, independent of the spontaneous within
      session decline in responding. Reinforcement enhancement by amphetamine, but not
      nicotine, was enhanced by concurrent subchronic food restriction.

PMID- 29199360
TI  - Editorial: Advancing Research on Child and Adolescent Psychopathology.

PMID- 29199359
TI  - Risk of venous thromboembolism among users of different anti-osteoporosis drugs:
      a population-based cohort analysis including over 200,000 participants from Spain
      and the UK.
AB  - : The venous thromboembolism risk among anti-osteoporotics is unknown. In this
      primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and
      0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK
      and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27
      (0.59-2.71)] in Spain, did not differ versus alendronate. INTRODUCTION: Most of
      the known adverse drug reactions described for anti-osteoporosis medication (AOM)
      have been described in studies comparing AOM users to non-users. We aimed to
      compare the risk of venous thromboembolism (VTE) among incident users of
      different AOM compared to alendronate (first line therapy). METHODS: Two cohort
      studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary
      care records separately. All patients aged >= 50 years with at least 1 year of
      data available and a new prescription or dispensation of AOM (date for therapy
      initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of
      raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts
      were identified according to first treatment: (1) alendronate, (2) other
      bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide.
      Participants were followed from the day after therapy initiation to the earliest
      of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180
      days), switching to an alternative AOM, drop-out, death, or end of study period.
      Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR
      95%CI) were estimated according to drug used. RESULTS: Overall, 2035/159,209
      (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate,
      adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other
      bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD
      and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for
      teriparatide in BIFAP. CONCLUSIONS: VTE risk during AO therapy did not differ by
      AOM drug use. Our data does not support an increased risk of VTE associated with
      strontium ranelate use in the community.

PMID- 29199361
TI  - Management of neuroendocrine tumors of unknown primary.
AB  - Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a
      significant number have metastatic disease at diagnosis mainly to the liver.
      Although in the majority of such cases the primary origin of the tumor can be
      identified, in approximately 11-22% no primary tumor is found and such cases are
      designated as NENs of unknown primary origin (UPO). This has significant
      therapeutic implications with respect to potentially resectable hepatic disease
      and/or application of appropriate medical therapy, either chemotherapeutic agents
      or targeted treatment, as the response to various treatments varies according to
      the origin of the primary tumor. This lack of tumor specific orientated treatment
      may also account for the relatively poorer prognosis of NENs of UPO compared to
      metastatic NENs with a known primary site. In the majority of cases the primary
      tumors are located in the small bowel and the lung, but a number may still elude
      detection. Occasionally the presence of a functional syndrome may direct to the
      specific tissue of origin but in the majority of cases a number of biochemical,
      imaging, histopathological and molecular modalities are utilized to help identify
      the primary origin of the tumor and direct treatment accordingly. Several
      diagnostic algorithms have recently been developed to help localize an occult
      primary tumor; however, in a number of cases no lesion is identified even after
      prolonged follow-up. It is expected that the delineation of the molecular
      signature of the different NENs may help identify such cases and provide
      appropriate treatment.

PMID- 29199362
TI  - Self-management interventions for cancer survivors: a systematic review.
AB  - PURPOSE: Many cancer survivors experience problems with persisting symptoms such
      as pain, fatigue, anxiety and depression post-treatment. Self-management
      interventions are recommended for cancer patients as they can help individuals
      identify and manage these continuing symptoms. This systematic review examines
      the type, content and impact of self-management interventions for cancer
      survivors on health outcomes such as activity participation, self-efficacy,
      quality of life and symptom management. METHODS: This was a systematic review of
      the English language scientific literature searched for randomised controlled
      trials (RCT), systematic reviews and meta-analyses of self-management programmes
      conducted with cancer survivors. Six databases were systematically searched.
      RESULTS: Initial searches yielded 2633 citations. Following screening and a risk
      of bias assessment, six studies were included in the final review. Heterogeneity
      of the interventions precluded meta-analysis. Three studies reported significant
      differences between groups in a number of areas including fatigue, physical
      functioning, distress and self-efficacy at their first follow-up assessment.
      These studies included two psychosocial interventions and one exercise and diet
      intervention. Not all findings were sustained across studies at follow-up
      assessment. CONCLUSION: It is not possible to draw definitive conclusions as to
      the impact the different types of self-management programme had on cancer
      survivors. The sustainability of the interventions reviewed was poor, suggesting
      that cancer survivors require interventions that can be applied into their daily
      activities.

PMID- 29199363
TI  - Development and preclinical trials of a wire-driven end effector device for
      frozen shoulder treatment.
AB  - Several different flexible end effectors have been developed to solve the problem
      of approaching the lesion in a minimally invasive surgery. In this paper, we
      developed a wire-driven end effector device to treat frozen shoulder. Since the
      device is for capsular release surgery, it has a suitable bend radius for the
      surgery. It is a cylindrical cannula that can fit various surgical tools and can
      be sterilized after use. The end effector is made of an elastic material called
      PAI (polyamide-imide) with its outer diameter and total length being 4 and 19 mm.
      It is controlled by wires that are connected to a motor. Through quantitative
      evaluation, we confirmed that the end effector can bend up to 90 degrees  in an
      upward or downward direction. Through qualitative evaluation, we confirmed that
      the device can easier access all regions of the glenoid in a shoulder model than
      conventional electrocautery. An experiment on a cadaver followed, which allowed
      us to discuss the real life performance, operation, and areas of improvement of
      the device with surgeons. From the experiments, we confirmed that our target
      region, the IGHL (inferior glenohumeral ligament), is within the reach of our
      device. The surgeon also evaluated that the control of the device caused no
      inconvenience.

PMID- 29199364
TI  - In situ reduced graphene oxide-based polyurethane sponge hollow tube for
      continuous oil removal from water surface.
AB  - Graphene oxide (GO) was prepared by using the natural graphite as raw materials
      via the modified Hummers' method and ultrasonic stripping method. GO was reduced
      online after its anchoring on the surface of polyurethane sponges by a dip
      coating method, then in situ reduced graphene oxide-based polyurethane (IRGOPU)
      sponges were fabricated. The characterizations of IRGOPU sponges were
      investigated using Field emission scanning electron microscope (FESEM), Fourier
      transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and
      contact angle measurement. The IRGOPU sponges had an adsorption capacity for a
      broad range of oils up to 21.7 ~ 55 g/g. A simulation experiment of large-scale
      oil spill using a simple IRGOPU sponge hollow tube component was designed. The
      process of continuous oil removal from water surface was quick and effective, and
      the oil/water separation efficiency could be up to 99.6%. The results indicated
      that the IRGOPU sponge hollow tube may be an optimum candidate for the oil/water
      separation of large-scale oil spill.

PMID- 29199366
TI  - Temporal-spatial variations and influencing factors of nitrogen in the shallow
      groundwater of the nearshore vegetable field of Erhai Lake, China.
AB  - Nitrogen export from the nearshore vegetable field of Erhai Lake seriously
      threatens the water quality of Erhai Lake, which is the second largest highland
      freshwater lake in Yunnan Province, China. Among the nitrogen flows into Erhai
      Lake, shallow groundwater migration is a major pathway. The nitrogen variation
      and influencing factors in the shallow groundwater of the nearshore vegetable
      field of Erhai Lake are not well documented. A 2-year field experiment was
      conducted to determine the concentrations of nitrogen species in the shallow
      groundwater and their influencing factors in the nearshore vegetable field of
      Erhai Lake. The results showed that concentrations of TN, NO3--N, and NO2--N
      gradually increased with increasing elevation and distance from Erhai Lake, but
      the opposite was observed for NH4+-N in the shallow groundwater. The
      concentrations of nitrogen species in the rainy season were greater than those in
      the dry season. NO3--N accounted for more than 79% of total nitrogen in shallow
      groundwater. Redundancy analysis showed that more than 70% of the temporal and
      spatial variations of nitrogen concentrations in the shallow groundwater were
      explained by shallow groundwater depth, and only approximately 10% of variation
      was explained by the factors of soil porosity, silt clay content of soil, and
      NH4+-N and NO3--N concentrations of soil (p < 0.05). The shallow groundwater
      depth had more notable effects on nitrogen concentrations in the shallow
      groundwater than other factors. This result will strongly support the need for
      further research regarding the management practices for reducing nitrogen
      concentrations in shallow groundwater.

PMID- 29199365
TI  - Volatile fatty acid augmentation and microbial community responses in anaerobic
      co-fermentation process of waste-activated sludge mixed with corn stalk and
      livestock manure.
AB  - This study investigated the acidogenic and microbiological perspectives in the
      anaerobic co-fermentation of waste-activated sludge (WAS) mixed with corn stalk
      (CS) and pig manure (PM). The volatile fatty acids (VFAs) increased dramatically
      to over 5000 mg COD/L accumulation just within 4-5 days with the feedstock carbon
      to nitrogen (C/N) ratio regulation of 20/1. The CS and PM addition enhanced the
      compressibility of fermentation residuals by increasing the particle distribution
      spread index (DSI). Moreover, the external carbon addition conduced to bacterial
      consortia diversity rising and uneven population distribution in the co
      fermentation, which contributed to VFAs accumulation potentially. The organic
      loading rate (OLR) correlated with bacterial community closely at the early stage
      (days 1-5), while the oxidation-reduction potential (ORP) and pH played more
      important roles on bacterial consortia at the terminal stage (days 6-10). The C/N
      ratio adjustment by CS and PM and proper optimizations of OLR, pH, and ORP at
      various running stages facilitated VFA accumulation during the co-fermentation
      operation.

PMID- 29199367
TI  - Flocculation performance of lignin-based flocculant during reactive blue dye
      removal: comparison with commercial flocculants.
AB  - A novel lignin-based flocculant (LBF) with superior flocculation performance was
      prepared from paper mill sludge in this work. The functional groups of LBF and
      alkaline lignin (AL) were determined by Fourier transform infrared spectroscopy
      (FTIR). The flocculation performance of LBF integrated with polyaluminum chloride
      (PAC) was tested in reactive dye wastewater treatment. Floc properties and color
      removals in multiple flocculation systems were discussed. Results indicated that
      the dye removal (93%) was greatly facilitated as the LBF was integrated with PAC
      (PAC + LBF). In addition, floc properties and color removals were significantly
      improved in the presence of Ca2+ and Mg2+. In contrary, flocculation performance
      was greatly restricted in the presence of SO42-. LBF was less pH sensitive and
      shear sensitive than polyacrylamide (PAM) due to the enhanced charge
      neutralization and bridging action. On the basis of that, LBF could be used as a
      promising flocculant in dye wastewater treatment.

PMID- 29199368
TI  - Testing ZnO nanoparticle ecotoxicity: linking time variable exposure to effects
      on different marine model organisms.
AB  - Zinc oxide nanoparticles (ZnO NPs) are increasingly used in several personal care
      products, with high potential to be released directly into marine environment
      with consequent adverse impact on marine biota. This paper aimed to compare the
      ecotoxicological effect of ZnO NPs (< 100 nm) towards three marine organisms
      widely used in toxicity assessment: an algal species (Dunaliella tertiolecta), a
      bioluminescent bacterium (Vibrio fischeri), and a crustacean (Artemia salina).
      Bulk ZnO (ZnO bulk, 200 nm) and ionic zinc were also investigated for
      understanding the role of size and of ionic release in the ZnO toxic action. To
      this aim, different ecotoxicological tests were used: the inhibition of
      bioluminescence with V. fischeri at three exposure times (5, 15, and 30 min); the
      D. tertiolecta growth inhibition at 24, 48, and 72 h; the A. salina mortality at
      24-96 h, and A. salina mortality and body growth each 3 days along chronic
      exposure (14 days). For all selected species, ZnO NPs toxicity was strictly
      dependent on the exposure time and different sensitivities were recorded: ZnO NPs
      were more toxic towards algae (EC50 2.2 mg Zn/L) but relatively less toxic
      towards bacteria (EC50 17 mg Zn/L) and crustaceans (EC50 96 h 58 mg Zn/L). During
      the 14-day chronic exposure of A. salina, ZnO NPs had a significant inhibition of
      vitality and body length (EC5014d 0.02 mg Zn/L), while the effect of ZnSO4 was
      not statistically different from the control. ZnO NP toxicity was related to zinc
      ions and to interactions of particle/aggregates with target organisms and
      therefore to NP behavior in the testing matrix and to the different testing time
      exposures.

PMID- 29199369
TI  - Hydraulic connection affects uranium distribution in the Gas Hure salt lake,
      Qaidam Basin, China.
AB  - The widespread hydraulic connection is necessary for the formation of a salt
      lake. However, only limited studies have ever been carried out to investigate the
      influence of the hydraulic connection on the distribution of elements around
      certain salt lake. In this study, a total of 66 water samples (including river
      water, stream water, spring water, brine, intercrystalline brine, well water, and
      drilling brine) were collected around the Gas Hure salt lake (GSKLH) to
      investigate the relationship between hydraulic connection and uranium (U)
      distribution via hydrochemistry and isotope (234U/238U, delta11B) techniques. The
      results suggested that the GSKLH was recharged by water from the Kulamulekesay
      and Atetikan rivers, groundwater (borehole brine and some intercrystalline
      brine), and deep fluid (some intercrystalline brine), with each contributing
      44.03%, 14.95%, and 41.02% of total recharge, respectively. The U-bearing rock
      was dominated mainly by silicates, carbonates, and evaporites in the high
      mountain area (region 1), overflow area (region 2), and plain area (region 3) of
      the GSKLH, respectively. In the GSKLH, the U distribution was strongly correlated
      with hydraulic connection and the U concentration was influenced by both
      groundwater flow system and flow velocity (represented by the gammaCl-/gammaCa2+
      ratio). Thus, U was enriched under the conditions of regional groundwater flow
      system and slow velocity in the GSKLH.

PMID- 29199370
TI  - Measuring medication adherence in older community-dwelling patients with
      multimorbidity.
AB  - PURPOSE: Older people with several chronic conditions require multiple drugs from
      different classes to be adequately treated. This study aims to: (i) measure
      medication adherence across multiple conditions and therapeutic drug groups in
      older community-dwelling patients, and (ii) examine the effect of multimorbidity
      on adherence. METHODS: This is a retrospective cohort study of medication
      adherence in 855 community-dwelling patients aged >= 70 years from 15 practices
      in Ireland using the Health Service Executive Primary Care Reimbursement Service
      (HSE-PCRS) pharmacy claims database. Multimorbidity was measured using the RxRisk
      V and by the number of different drug classes. The RxRisk-V algorithm classifies
      prescription drug fills into 45 chronic disease classes for older populations
      based on the WHO Anatomical Therapeutic Chemical classification system. Adherence
      to medications was assessed by: (i) calculating the average medication possession
      ratio (MPR) per patient and (ii) an MPR< 80%. RESULTS: The overall median MPR for
      the cohort was 0.83 (IQR 0.69, 0.91). The conditions with the highest MPRs were
      hypothyroidism (mean MPR = 0.88, SD = 0.20) and type 2 diabetes (mean MPR = 0.83,
      SD = 0.19), followed by heart disease. On average, 20-40% of patients were non
      adherent (MPR < 80%) across all conditions. There was an inverted U-shaped
      relationship between the mean MPR and number of morbidities and drug classes.
      Adherence varied per patients' morbidity burden, with higher adherence for
      certain combinations of chronic conditions. CONCLUSION: In total, 31% of older
      patients with multimorbidity were non-adherent to their medication but adherence
      levels varied across treatment categories and chronic conditions.

PMID- 29199371
TI  - Molecular detection and prevalence of Cryptosporidium spp. infections in two
      types of domestic farm animals in the Qinghai-Tibetan Plateau Area (QTPA) in
      China.
AB  - The objective of this study was to determine the prevalence of Cryptosporidium
      species infections in young cattle and sheep in the north-eastern part of the
      Qinghai-Tibetan Plateau Area (QTPA), north-western China. A total number of 454
      faecal samples (389 from cattle and 65 from sheep) were collected and
      investigated to determine the prevalence of Cryptosporidium spp. oocysts.
      Cryptosporidium spp. infections detected in cattle (n = 56 positive samples) and
      sheep (n = 4 positive samples) were as following: C. andersoni (16/56, 28.6%) was
      the dominant species, followed by C. canis (9/56, 16.1%), C. bovis (9/56, 16.1%),
      C. hominis (8/56, 14.3%), C. struthionis (7/56, 12.5%), C. ryanae (5/56, 8.9%),
      and C. serpentis (2/56, 3.6%). Two Cryptosporidium species were detected in
      sheep: C. parvum (2/4) and C. canis (2/4). There were no mixed infections. C.
      hominis, C. struthionis, and C. serpentis are reported in domestic animals for
      the first time at the QTPA of China and our results indicate an anthropozoonotic
      transmission of C. hominis. The identification of Cryptosporidium spp. in
      domestic animals warrants better care of the farm animals in order to avoid
      contamination in vulnerable animal and human populations.

PMID- 29199372
TI  - Comparative assessment of recombinant and native immunogenic forms of Fasciola
      hepatica proteins for serodiagnosis of sheep fasciolosis.
AB  - Laboratory diagnosis of sheep fasciolosis is commonly performed by coprological
      examinations; however, this method may lead to false negative results during the
      acute phase of the infection. Furthermore, the poor sensitivity of coprological
      methods is considered to be a paradox in the chronic phase of the infection. In
      this study, we compared the immunoreactivity of native and recombinant forms of
      Fasciola hepatica excretory/secretory antigens and determined their capabilities
      for the development of F. hepatica-specific immunoassays. Immunoreactivity and
      specificity of recombinant and native forms of F. hepatica antigens, including
      fatty acid binding protein (FABP), glutathione-S-transferase (GST), and cathepsin
      L-1 (CL1), in parallel with native forms of FABP and GST, were studied for
      serodiagnosis of the chronic form of sheep fasciolosis, individually or in
      combination with each other by enzyme-linked immunosorbent assays (ELISA). The
      correlation of the findings was assessed by receiver-operator characteristic
      (ROC); furthermore, the specificity and sensitivity were assessed by Youden's J.
      Serologic cross-reactivity was evaluated using samples from healthy sheep (n =
      40), Fasciola-infected sheep (n = 30), and sheep with other parasitic infections
      (n = 43). The FABPs were determined to be greater than 95% sensitive for F.
      hepatica serodiagnosis. The most desirable diagnostic recombinant antigen was
      rCL1, which showed 100% sensitivity and 97% specificity in ELISA and was capable
      of discriminating the positive and negative samples by maximum Youden's J
      results. We conclude that rCL1 can be used for routine serodiagnosis of chronic
      fasciolosis. Thus, it could be advantageous in development of immunoassays for
      screening of ovine herds in fasciolosis-endemic areas and as a reliable agent for
      detection of fasciolosis in non-endemic regions.

PMID- 29199374
TI  - Who are we and where are we Going: from Past Myths to Present Politics.
AB  - Social groups, and the social identities which people develop as part of them,
      are often experienced as stable and continuous over time. Thus, countries
      experiencing rapid socio-political change often face the challenge of re
      constructing the meaning of the social group to adapt to the demands of the
      present, while simultaneously making this re-construction appear as a natural
      progression of 'our' historical journey. In the present paper, I ask the question
      of how, in times of socio-political change, the past is used in the present, and
      the implications this has for how individuals represent their nation's future.
      Drawing on Serbia and its political movement towards EU integration, the present
      article illustrates how developed and legitimized historical narratives, linked
      to the myth of origin of a nation, become utilized to frame present challenges.
      In doing so, it allows for uncertainties in the present to become anchored in
      established historical narratives, which in turn have consequences for which
      political actions are deemed acceptable and legitimate for the future.

PMID- 29199373
TI  - Dentoskeletal and soft tissue changes in class II subdivision treatment with
      asymmetric extraction protocols.
AB  - BACKGROUND: This study cephalometrically compared the dentoskeletal and soft
      tissue changes consequent to one and three-premolar extraction protocols of class
      II subdivision malocclusion treatment. METHODS: A sample of 126 lateral
      cephalometric radiographs from 63 patients was selected and divided into two
      groups. Group 1 consisted of 31 type 1 class II subdivision malocclusion patients
      treated with asymmetric extractions of two maxillary premolars and one mandibular
      premolar on the class I side, with an initial mean age of 13.58 years. Group 2
      consisted of 32 type 2 class II subdivision malocclusion patients treated with
      asymmetric extraction of one maxillary first premolar on the class II side, with
      an initial mean age of 13.98 years. t test was used for intergroup comparison at
      the pre- and posttreatment stages and to compare the treatment changes. RESULTS:
      Group 1 had greater maxillomandibular sagittal discrepancy reduction and greater
      maxillary first molar extrusion. Group 2 had mandibular incisor labial
      inclination and protrusion, and group 1 had mandibular incisor lingual
      inclination and retraction. Maxillary molar asymmetry increased in group 2, while
      mandibular molar asymmetry increased in group 1. CONCLUSIONS: The treatment
      changes produced by these two class II subdivision protocols are different to
      adequately satisfy the different needs for types 1 and 2 class II subdivision
      malocclusions.

PMID- 29199375
TI  - Using percolation networks to incorporate spatial-dose information for assessment
      of complication probability in radiotherapy.
AB  - This study investigates an extension of recent cluster based methods of assessing
      the probability of complication in normal organs following radiotherapy treatment
      which delivers a spatially non-uniform radiation dose distribution. Current
      methods of assessing this complication probability are spatially degenerate and
      do not adequately assess the contiguity of damage done to tissue. Therefore, new
      measures of assessing complication after radiation exposure have been proposed
      for parallel and serial type organs. In parallel organs an interaction between
      cells within a functional subunit is stipulated and complication is regarded as a
      weighted sum of all clusters in the organ. This allows the assessment to account
      for all damage to the tissue whilst emphasising the importance of damage that
      accumulates into large and connected spatial regions addressing a deficiency in
      the current method of calculating complication probabilities. Several spatially
      varying doses were analysed and simulated in silico. The simulations produce
      complication risk estimates for homogeneous dose distributions that are
      comparable to empirical results but which deviate with any dose inhomogeneity.
      The simulations also show that the standard method of dose transformation to an
      effective uniform dose is not valid in cluster based models.

PMID- 29199376
TI  - Total Fatty Acid Content Determination of Whole Microalgal Biomass Using In Situ
      Transesterification.
AB  - The aliphatic chains of fatty acids are the most prominent and potentially the
      highest value precursor constituents of algal biomass, and thus accurately
      quantifying the algal biomass total fatty acid content is a prerequisite for
      comparing algal strains, growth conditions, and processes. Direct, acid-catalyzed
      transesterification of whole microalgal biomass is a simple, effective, and
      widely used method to determine the fatty acid content in whole algal biomass.
      Such a direct transesterification procedure typically covers the following steps:
      first, solubilizing the lipids in the biomass matrix and then liberating the
      fatty acids to make these available for catalytic upgrading to fatty acid methyl
      esters (FAMEs), subsequent extraction into hexane, and then quantification by gas
      chromatography. The method we describe here requires less than 10 mg of biomass
      per sample and is considered high-throughput and highly accurate.

PMID- 29199377
TI  - Total Carbohydrate Content Determination of Microalgal Biomass by Acid Hydrolysis
      Followed by Spectrophotometry or Liquid Chromatography.
AB  - The carbohydrate fraction of microalgal biomass is complex and consists of a
      combination of neutral, acidic, amino sugars, and sugar alcohols. These
      carbohydrate amalgamations can be difficult to accurately quantify with the most
      analytical carbohydrate determination techniques. The method described here
      provides a straightforward two-step sulfuric acid hydrolysis followed by soluble
      carbohydrate quantification by either a spectrophotometric method (based on
      aldehyde functional group derivatization), for an overall combined monomeric
      sugar concentration determination, or a liquid chromatography method, for a more
      specific monomeric sugar profile.

PMID- 29199378
TI  - Distribution of pathogenicity island markers and virulence factors in new
      phylogenetic groups of uropathogenic Escherichia coli isolates.
AB  - The present study was aimed at investigating the relationship between the new
      Clermont's phylogenetic groups, virulence factors, and pathogenicity island
      markers (PAIs) among uropathogenic Escherichia coli (UPEC) in Iran. This cross
      sectional study was carried out on 140 UPEC isolates collected from patients with
      urinary tract infections in Bushehr, Iran. All isolates were subjected to
      phylogenetic typing using a new quadruplex-PCR method. The presence of PAI
      markers and virulence factors in UPEC strains was evaluated by multiplex PCR. The
      most predominant virulence gene was fimH (85%), followed by iucC (61.4%), papC
      (38.6%), hlyA (22.1%), cnf-1 (18.6%), afa (10.7%), papG and neuC (each 9.3%),
      ibeA (3.6%), and sfa/foc (0.7%). The most common phylogenetic group was related
      to B2 (39.3%), and the least common to A (0.7%). The most prevalent PAI marker
      was PAI IV536 (77.14%), while markers for PAI III536 (13.57%), PAI IIJ96
      (12.86%), and PAI II536 (12.14%) were the least frequent among the UPEC strains.
      Meanwhile, the PAI IJ96 marker was not detected. There was a significant
      association between the phylogenetic group B2 and all the studied virulence genes
      and PAI markers. To our knowledge, this is the first study to compare the
      relationship between new phylogenetic groups, virulence genes and PAI markers in
      UPEC strains in Iran. The phylogenetic group B2 was predominantly represented
      among the studied virulence genes and PAI markers, indicating the preference of
      particular strains to carry virulence genes.

PMID- 29199379
TI  - Mini-subvastus versus medial parapatellar approach for total knee arthroplasty: a
      prospective randomized controlled study.
AB  - PURPOSE: Whether minimally invasive total knee arthroplasty (MIS-TKA) could offer
      better and faster recovery without the deviation of post-operative prosthesis
      position and limb alignment is still controversial. This prospective and
      randomized study was conducted to compare the clinical and radiological outcomes
      between patients who underwent the mini-subvastus approach of MIS-TKA and those
      who underwent the medial parapatellar approach of traditional TKA. METHODS: Fifty
      patients, including 50 knees, who required TKA due to osteoarthritis were
      randomized to the mini-subvastus group (group I) or the medial parapatellar group
      (group II). All patients accepted the same method of anaesthesia, equal support
      therapy and identical rehabilitation exercise after surgery. The evaluation
      system included operation time, tourniquet time, blood loss, skin incision length
      in flexion, straight leg raising time, the time of lower limb muscle strength up
      to grade 4, the time of walking with aid or without aid, the time of walking up
      and down the stairs, the active flexion angle, range of movement (ROM), the Knee
      Society Scores (KSS), visual analogue score for pain (VAS), hospital stays and
      radiographic outcomes. RESULTS: The mini-subvastus approach offered smaller skin
      incision length in flexion, but at the cost of operation time (P < 0.001). No
      significant difference was found in tourniquet time and blood loss. The patients
      in group I could achieve straight leg raising, the lower limb muscle strength up
      to grade 4, walking with or without aid, and walking up and down the stairs
      earlier (P < 0.001). The active flexion angle, ROM, VAS and KSS in group I were
      superior to those in group II until six months post-operatively (P < 0.001), but
      the differences was not apparent at 12 months post-operatively. More importantly,
      there was no significant difference between the two groups on radiological
      outcomes (P > 0.05). CONCLUSIONS: The mini-subvastus approach could offer faster
      recovery, less pain and shorter hospital stays without compromising the
      principles of proper prosthesis position and limb alignment compared with the
      medial parapatellar approach.

PMID- 29199380
TI  - Liver resection for HCC outside the BCLC criteria.
AB  - PURPOSE: Surgical resection still remains the mainstay of management of
      hepatocellular carcinoma (HCC). At present, Barcelona clinic liver cancer (BCLC)
      staging is the most widely used tool to guide treatment; however, criteria for
      offering surgery as curative treatment are restrictive. We aimed to evaluate
      short-term and long-term outcomes of HCC after resection, even for patients
      outside BCLC criteria for resection. METHODS: Data was collected from a
      prospective database from GI and HPB Department, Tata Memorial Hospital, Mumbai.
      Study period was from June 2010 to June 2015. RESULTS: One hundred three patients
      of HCC were operated during this period, of which 100 underwent complete
      resection. Patients were staged according to the BCLC classification (BCLC stage
      A-25, B-64, C-11). Preoperative therapy was administered in 36 (36%) patients. At
      median follow-up of 21 months, overall 3-year survival for BCLC stages A, B, and
      C was 55.2, 62.7, and 37.5%, respectively. CONCLUSION: In today's era of liver
      transplantation, resection (especially for larger tumors) may still be the
      preferred treatment option, considering problems and difficulties in donor
      availability, cost, and long waiting list for liver transplant. With evolving
      modern surgical technique, long-term survival benefit can be achieved with
      acceptable safety in most BCLC stage B and selected BCLC stage C patients and
      those who either do not fit into the transplant criteria or cannot afford
      transplant. Carefully designed trials are required to further elucidate these
      results.

PMID- 29199382
TI  - Correction to: Prevalence of HIV-1 transmitted drug resistance in recently
      infected, treatment-naive persons in the Southwest of Iran, 2014-2015.
AB  - The author would like to correct the error in the online published article. The
      correct details are given below for your reading.

PMID- 29199381
TI  - Neurosurgical management of cavernous malformations located at the foramen of
      Monro.
AB  - Cavernous malformations (CMs) located at the foramen of Monro (FM) are relatively
      rare benign vascular malformations. Knowledge of FM CM is poor. The aims of this
      study were to describe the incidence, clinical presentation, radiological
      features, surgical approaches, and neurological outcomes for FM CM patients and
      to discuss the treatment strategy for this disease. We present a series of nine
      FM CM patients (four males, five females; mean age 29.3 years) who were treated
      at a single neurosurgical center. FM CM accounted for 0.56% of the entire series
      of the central nervous system (CNS) CMs. Headache accompanied by nausea and
      vomiting was the most common initial symptom (55.6%). The mean preoperative
      Karnofsky Performance Scale (KPS) score was 84.4 (range 70-100). In all but one
      patient, the lesions were surgically resected. Postoperatively, two patients
      developed obstructive hydrocephalus, and one experienced motor aphasia and right
      hemiparesis. At the time of discharge, the KPS score improved to a mean of 88.9.
      Follow-up period after diagnosis was 18 to 131 months (mean 69.7 months); all the
      patients were considered to be in excellent clinical condition. FM CMs are rare
      and challenging lesions; they have a female predilection. The most common
      clinical manifestations of FM CM are the symptoms of mass effect. The seizure
      risk of FM CMs seems to be significantly lower than that of general
      intraventricular CMs. Early surgical intervention should be offered to
      symptomatic cases, and gross total resection is associated with favorable
      neurological outcomes.

PMID- 29199383
TI  - Combined corticosterone treatment and chronic restraint stress lead to depression
      associated with early cognitive deficits in mice.
AB  - Many models, such as chronic mild stress, chronic stress or chronic
      corticosterone injections are used to induce depression associated with cognitive
      deficits. However, the induction period in these different models is still long
      and face constraints when it is short such as in the chronic mild stress done in
      a minimum period of 21 days. This study aimed to characterize a model of
      depression with early onset cognitive deficit. 14 days combined chronic injection
      of corticosterone followed by 2 h restraint stress using a restrainer was used to
      induce depression with early cognitive deficit onset. The forced swim test,
      sucrose test and plasma corticosterone concentration were used to assess
      depression-like characteristics. The Morris water maze, novel object recognition
      task, as well as hippocampal acetylcholinesterase activity were used to assess
      cognitive deficit. The combined corticosterone injection + chronic restraint
      stress group presented with marked depression-like behaviour and a higher plasma
      corticosterone concentration compared to corticosterone injection alone and
      restraint stress alone. It also showed an alteration in the learning process,
      memory deficit as well as increased acetylcholinesterase activity compared to
      corticosterone injection and restraint stress alone groups. These findings
      suggest that the combined corticosterone administration and chronic restraint
      stress can be used not only as an animal model for severe depression, but also
      for depression with early onset cognitive deficit.

PMID- 29199384
TI  - Low-intensity LED therapy (658 nm) on burn healing: a series of cases.
AB  - The objective of this study was to evaluate the effects of LED on burns healing.
      Five patients with skin burns were submitted to photobiomodulation by LED, GaAsIP
      diode, (lambda 658 nm) with 40 mW, 7 J/cm2 on every other day. Biopsies of burned
      skin were performed and the healing process was photographed. Patients with
      bilateral burns were used as self-control, having one limb being irradiated and
      the contralateral limb irradiated with placebo. The burns treated with LED showed
      higher epithelization, with keratinocytes and fibroblasts proliferation,
      increased collagen synthesis, decreased pain, and pruritus. In conclusion, there
      was a faster clinical improvement in the irradiated limbs.

PMID- 29199386
TI  - Triangle of AKT2, miRNA, and Tumorigenesis in Different Cancers.
AB  - AKT (AK mouse plus Transforming or Thymoma) is a frequent oncogene expressed in
      most tissues which includes three isoforms AKT1, AKT2, and AKT3. Hyperactivation
      of AKT signaling is a central key in many human cancer progressions, through
      modulating angiogenesis, tumor growth, and cell migration, invasion, metastasis,
      and chemoresistance. Among all three isoforms, AKT2 is most related to cancer
      cell invasion, metastasis, and survival. Amplification and overexpression of AKT2
      have been shown in many cancers. Accumulating evidence shows the potential role
      of different miRNA involvements in cancer progression by activating or
      suppressing AKT2 expression. In an in-depth literature review, we focus on the
      role of AKT2 activation and its consequences on the tumor progression in
      different cancers. In addition, we describe the function of numerous AKT2-related
      miRNAs which are important in various cancers as diagnostic, prognostic, and
      therapeutic markers.

PMID- 29199385
TI  - Resistance exercise enhances oxygen uptake without worsening cardiac function in
      patients with systolic heart failure: a systematic review and meta-analysis.
AB  - Recent literature suggests that resistance training (RT) improves peak oxygen
      uptake ([Formula: see text] peak), similarly to aerobic exercise (AE) in patients
      with heart failure (HF), but its effect on cardiac remodeling is controversial.
      Thus, we examined the effects of RT and AE on [Formula: see text] peak and
      cardiac remodeling in patients with heart failure (HF) via a systematic review
      and meta-analysis. MEDLINE, EMBASE, Cochrane Library and CINAHL, AMEDEO and PEDro
      databases search were extracted study characteristics, exercise type, and
      ventricular outcomes. The main outcomes were [Formula: see text] peak (ml kg-1
      min-1), LVEF (%) and LVEDV (mL). Fifty-nine RCTs were included. RT produced a
      greater increase in [Formula: see text] peak (3.57 ml kg-1 min-1, P < 0.00001, I
      2 = 0%) compared to AE (2.63 ml kg-1 min-1, P < 0.00001, I 2 = 58%) while
      combined RT and AE produced a 2.48 ml kg-1 min-1 increase in [Formula: see text];
      I 2 = 69%) compared to control group. Comparison among the three forms of
      exercise revealed similar effects on [Formula: see text] peak (P = 0.84 and 1.00,
      respectively; I 2 = 0%). AE was associated with a greater gain in LVEF (3.15%; P
      < 0.00001, I 2 = 17%) compared to RT alone or combined exercise which produced
      similar gains compared to control groups. Subgroup analysis revealed that AE
      reduced LVEDV (- 10.21 ml; P = 0.007, I 2 = 0%), while RT and combined RT and AE
      had no effect on LVEDV compared with control participants. RT results in a
      greater gain in [Formula: see text] peak, and induces no deleterious effects on
      cardiac function in HF patients.

PMID- 29199387
TI  - Early marginal bone stability of dental implants placed in a transalveolarly
      augmented maxillary sinus: a controlled retrospective study of surface
      modification with calcium ions.
AB  - BACKGROUND: Recently, components of the extracellular cellular matrix have been
      assessed to enhance the biological response to dental implants. This study aims
      to assess the effect of surface modification with calcium ions on the early
      marginal bone loss of dental implants placed in a transalveolarly augmented
      maxillary sinus. METHODS: A retrospective study of transalveolar sinus floor
      augmentation was conducted in a single private dental clinic. The predictor
      variable was the surface of the dental implant. The primary outcome was the
      marginal bone loss. The secondary outcomes were the intraoperative complications
      and the dental implant failure. Descriptive analysis was performed for patients'
      demographic data and implant details. RESULTS: Fifty-one patients with a mean age
      of 58 +/- 11 years had a mean follow-up time of 13 months. Thirty-four dental
      implants had a Ca2+-modified hydrophilic surface, and 31 had no Ca2 (control).
      The experimental group showed a statistically significant lower marginal bone
      loss (0.36 +/- 0.42 vs 0.61 +/- 0.39 mm). However, there were no statistically
      significant differences in the implant survival. No implant failed in the
      experimental group while two implants failed in the control group. CONCLUSIONS:
      The modification of an acid-etched surface with calcium ions seems to reduce the
      marginal bone remodeling around the dental implants, placed after transalveolar
      sinus floor elevation.

PMID- 29199388
TI  - Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a
      network meta-analysis of randomized trials.
AB  - PURPOSE: Stress ulcer prophylaxis (SUP) is commonly prescribed in the intensive
      care unit. However, data from systematic reviews and conventional meta-analyses
      are limited by imprecision and restricted to direct comparisons. We conducted a
      network meta-analysis of randomized clinical trials (RCTs) to examine the safety
      and efficacy of drugs available for SUP in critically ill patients. METHODS: We
      searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled
      Trials through April 2017 for randomized controlled trials that examined the
      efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor
      antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date
      or language restrictions were applied. Data on study characteristics, methods,
      outcomes, and risk of bias were abstracted by two reviewers. RESULTS: Of 96
      potentially eligible studies, we included 57 trials enrolling 7293 patients. The
      results showed that PPIs are probably more effective for preventing clinically
      important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95%
      confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13,
      0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence).
      There were no convincing differences among H2RA, sucralfate, and placebo. PPIs
      probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27;
      95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR
      1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar
      across interventions (moderate quality). Estimates of baseline risks of bleeding
      varied significantly across studies, and only one study reported on Clostridium
      difficile infection. Definitions of pneumonia varied considerably. Most studies
      on sucralfate predate pneumonia prevention strategies. CONCLUSIONS: Our results
      provide moderate quality evidence that PPIs are the most effective agents in
      preventing CIB, but they may increase the risk of pneumonia. The balance of
      benefits and harms leaves the routine use of SUP open to question.

PMID- 29199389
TI  - Development and Evaluation of a Telephone Communication Protocol for the Delivery
      of Personalized Melanoma Genomic Risk to the General Population.
AB  - Communicating personalized genomic risk results for common diseases to the
      general population as a form of tailored prevention is novel and may require
      alternative genetic counseling service delivery models. We describe the
      development and evaluation of a communication protocol for disclosing melanoma
      genomic risk information to the asymptomatic general population and assess
      participants' satisfaction and acceptability. Participants (n = 117) were aged 22
      69 years, living in New South Wales, Australia and unselected for family history.
      They provided a saliva sample and had genomic testing for melanoma for low to
      moderate penetrant melanoma susceptibility variants in 21 genes. Participants
      could choose to receive their results from a genetic counselor via telephone,
      followed by a mailed booklet or to receive their risk result via mailed booklet
      only with a follow-up call for those at high risk. A follow-up questionnaire was
      completed by 85% of participants 3-months later. Most participants (80%) elected
      to receive their result via telephone. Participants were highly satisfied with
      the delivery of results (mean 3.4 out of 4, standard deviation 0.5), and this did
      not differ by delivery mode, risk category, age or sex. On follow-up, 75%
      accurately recalled their risk category, 6% indicated a preference for a
      different delivery mode, either electronic or face-to-face. The process of
      disclosing genomic risk results to the general population over the telephone with
      accompanying written material was feasible and acceptable, and may be useful for
      communicating polygenic risk for common diseases in the context of increasing
      demands for genomic testing.

PMID- 29199391
TI  - Variations in the practice of molecular radiotherapy and implementation of
      dosimetry: results from a European survey.
AB  - BACKGROUND: Currently, the implementation of dosimetry in molecular radiotherapy
      (MRT) is not well investigated, and in view of the Council Directive
      (2013/59/Euratom), there is a need to understand the current availability of
      dosimetry-based MRT in clinical practice and research studies. The aim of this
      study was to assess the current practice of MRT and dosimetry across European
      countries. METHODS: An electronic questionnaire was distributed to European
      countries. This addressed 18 explicitly considered therapies, and for each
      therapy, a similar set of questions were included. Questions covered the number
      of patients and treatments during 2015, involvement of medical specialties and
      medical physicists, implementation of absorbed dose planning, post-therapy
      imaging and dosimetry, and the basis of therapy prescription. RESULTS: Responses
      were obtained from 26 countries and 208 hospitals, administering in total 42,853
      treatments. The most common therapies were 131I-NaI for benign thyroid diseases
      and thyroid ablation of adults. The involvement of a medical physicist (mean over
      all 18 therapies) was reported to be either minority or never by 32% of the
      responders. The percentage of responders that reported that dosimetry was
      included on an always/majority basis differed between the therapies and showed a
      median value of 36%. The highest percentages were obtained for 177Lu-PSMA therapy
      (100%), 90Y microspheres of glass (84%) and resin (82%), 131I-mIBG for
      neuroblastoma (59%), and 131I-NaI for benign thyroid diseases (54%). The majority
      of therapies were prescribed based on fixed-activity protocols. The highest
      number of absorbed-dose based prescriptions were reported for 90Y microsphere
      treatments in the liver (64% and 96% of responses for resin and glass,
      respectively), 131I-NaI treatment of benign thyroid diseases (38% of responses),
      and for 131I-mIBG treatment of neuroblastoma (18% of responses). CONCLUSIONS:
      There is a wide variation in MRT practice across Europe and for different
      therapies, including the extent of medical-physicist involvement and the
      implementation of dosimetry-guided treatments.

PMID- 29199392
TI  - Porous titanium granules in the treatment of peri-implant osseous defects-a 7
      year follow-up study.
AB  - BACKGROUND: A great number of different treatment protocols for peri-implantitis
      have been suggested but there is no consensus regarding the most effective
      intervention. The aim of the present study was to evaluate the long-term clinical
      and radiographic results from a study on peri-implant osseous defect
      reconstruction. Patients having participated in a randomized clinical study 7
      years earlier were invited for a re-examination. The treatment procedures
      included open flap debridement (OFD) with or without defect reconstruction with
      porous titanium granules (PTGs). Clinical parameters (probing pocket depth and
      bleeding on probing) and radiographic measurements were registered. FINDINGS: Of
      the original 32 patients, 12 patients with 12 implants were finally examined
      after 7 years (7.3 years [6.7-8]). Patients had been maintained one to two times
      yearly. The PTG group showed a mean probing pocket depth of 4.3 mm +/- 2.4
      compared with 3.5 mm +/- 1.2 in the OFD group, at the deepest site. The change
      between the 12 months and the 7-year examination was similar in both groups. Five
      of the test implants and five of the control implants had at least one site with
      positive bleeding on probing score. The mean radiographic defect depth change as
      compared to 12 months was an increase of 1.9 mm +/- 2.0 in the PTG group and a
      mean radiographic defect depth increase of 1.3 mm +/- 1.4 in the OFD group. Due
      to the small number of patients, a statistical analysis was not performed, but
      the results indicated a minimal difference in osseous defect depth as compared
      with baseline and between groups. No PTG exposed to the oral cavity was observed,
      but the graft particles were seemingly scattered in the peri-implant soft tissue.
      CONCLUSIONS: This long-term follow-up of surgical treatment of peri-implant
      osseous defects showed unpredictable results.

PMID- 29199393
TI  - A public health outbreak management framework applied to surges in opioid
      overdoses.
AB  - Over the past decade, Canada and the United States have been facing an epidemic
      of harms from prescription opioids. More recently, opioid-naive individuals have
      been exposed to illicit opioids through adulterated combination products. This
      has resulted in sudden surges of opioid-related mortality. A proactive public
      health solution is needed to prevent further death. We propose examining these
      surges in opioid overdoses as outbreaks and investigating them in a similar way
      to an outbreak of an infectious disease. An epidemiologic investigation model for
      opioid overdose outbreaks, that could be modified by other public health
      agencies, is discussed.

PMID- 29199390
TI  - Autoimmune/inflammatory syndrome induced by adjuvants-ASIA-related to
      biomaterials: analysis of 45 cases and comprehensive review of the literature.
AB  - Systemic autoimmune or granulomatous disorders related to biomaterials of human
      use have rarely been described. The aim of this study was to report cases of
      autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to
      biomaterial injections and prostheses, mainly silicone, hyaluronic acid,
      acrylamides and methacrylate compounds in a Spanish patient cohort. This study is
      a retrospective analysis of clinical, laboratory, histopathological and follow-up
      data of 45 cases of patients suffering from late-onset, non-infectious
      inflammatory/autoimmune disorders related to bioimplants. Late onset was defined
      as 3 months or more post injection. Data were obtained through a further non
      systematic but comprehensive review of the literature. Forty-five cases of late
      onset adverse reactions related to biomaterial injections or prostheses were
      reviewed. All cases had systemic complaints that could be categorised as ASIA. In
      all but four patients, inflammatory features at the implantation site preceded
      distant or systemic manifestations. Abnormal blood tests were common. Localised
      inflammatory nodules and panniculitis in 40/45 (88.88%) evolved into a variety of
      disorders, viz., primary biliary cirrhosis, Sjogren's syndrome, sarcoidosis,
      human adjuvant disease, vasculitis, inflammatory bowel syndrome and inflammatory
      polyradiculopathy. Five (11.11%) cases presented primarily with systemic
      autoimmune disorders. Biomaterials and prostheses can provoke late-onset systemic
      autoimmune disorders fulfilling ASIA criteria, or present primarily
      local/regional inflammatory reactions that may eventually evolve into systemic
      autoimmune and/or granulomatous disorders which fall under ASIA.

PMID- 29199394
TI  - Trends in Florida's Prescription Drug Monitoring Program registration and
      utilization: Implications for increasing voluntary use.
AB  - OBJECTIVE: Effective use of state prescription drug monitoring programs (PDMPs)
      to track controlled substance prescribing and dispensing may help mitigate the
      current opioid crisis. Our objective was to examine trends in registration for
      and use of Florida's PDMP by physicians and pharmacists, from 2013 to 2016. We
      discuss implications for PDMP uptake and policy. DESIGN: Key measures, such as
      cumulative number of registrants per license type and monthly utilization
      intensity, are presented. A time series forecasting approach was used to (1)
      model the monthly count of new PDMP registrants and users from January 2013 to
      December 2016 and (2) estimate cumulative registration totals after 1 year.
      SETTING: Florida. RESULTS: As of November 2016, there were 16,498 physicians
      (representing 31 percent of Drug Enforcement Administration licensees) and 17,241
      pharmacists registered with the PDMP, representing 21 and 57 percent of
      professional licensees, respectively. Of note, the PDMP's designation as a
      "specialized registry" for electronic medical record "meaningful use" criteria
      led to a nearly sevenfold increase in physician registrations in a single month.
      In November 2016, pharmacists displayed a higher past-month PDMP utilization rate
      (52.2 percent vs 30.1 percent), while physicians displayed a higher past-month
      PDMP utilization intensity (58.1 vs. 36.1 queries per user). Approximately 25,000
      physicians and 31,000 pharmacists must register by the end of 2017 to meet
      national policy goals. CONCLUSION: PDMP registration among physicians and
      pharmacists is limited, and the use of the PDMP among registrants is more limited
      still. Our findings suggest that Florida will not meet national policy goals for
      registrants by the end of 2017, although new initiatives may alter this trend.
      Allowing the PDMP to help prescribers meet other professional needs, such as
      "meaningful use" or similar efforts, may be effective in increasing PDMP use.

PMID- 29199395
TI  - Projecting the cost, utilization, and patient care impact of prescribing extended
      release non-abuse-deterrent opioids to chronic pain patients.
AB  - OBJECTIVES: To estimate healthcare resource utilization, associated costs, and
      number needed to harm (NNH) from a physician's decision to prescribe extended
      release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a
      chronic pain population. DESIGN: A 12-month probabilistic simulation model was
      developed to estimate the reduction of misuse and/or abuse from a physician's
      prescribing decisions for 10,000 patients. Model inputs included probabilities
      for opioid misuse and/or abuse-related events, opioid discontinuation, and
      switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs
      were obtained from positive subjective measures using human abuse liability
      studies. The model was run separately for commercial, Medicare, Medicaid, and
      Veterans Administration (VA) populations. The difference in healthcare resource
      utilization and associated costs (2015 USD) between the ADO and non-ADO
      simulations was calculated. NNH for non-ADO was also calculated. RESULTS: Misuse
      and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223
      1,410 and associated costs ranged from $20-$98 per patient for commercial and
      Medicare populations, respectively. Prescribing ER ADOs were associated with 87,
      289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21,
      and $29 per patient in commercial, VA, Medicaid, and Medicare populations,
      respectively. NNH ranged from 185 in the commercial population to 40 in the
      Medicare population. Results were sensitive to decreases in the probability of
      misuse and/or abuse events but showed reductions. CONCLUSIONS: A physician's
      decision to prescribe ER ADOs could lead to large reductions in misuse and/or
      abuse-related events and associated costs across many patient populations.

PMID- 29199396
TI  - Educational intervention for physicians to address the risk of opioid abuse.
AB  - OBJECTIVE: To evaluate the impact of a pilot intervention for physicians to
      support their treatment of patients at risk for opioid abuse. SETTING, DESIGN AND
      PATIENTS, PARTICIPANTS: Patients at risk for opioid abuse enrolled in Medicare
      plans were identified from July 1, 2012 to April 30, 2014 (N = 2,391), based on a
      published predictive model, and linked to 4,353 opioid-prescribing physicians.
      Patient-physician clusters were randomly assigned to one of four interventions
      using factorial design. INTERVENTIONS: Physicians received one of the following:
      Arm 1, patient information; Arm 2, links to educational materials for diagnosis
      and management of pain; Arm 3, both patient information and links to educational
      materials; or Arm 4, no communication. MAIN OUTCOME MEASURES: Difference-in
      difference analyses compared opioid and pain prescriptions, chronic high-dose
      opioid use, uncoordinated opioid use, and opioid-related emergency department
      (ED) visits. Logistic regression compared diagnosis of opioid abuse between cases
      and controls postindex. RESULTS: Mailings had no significant impact on numbers of
      opioid or pain medications filled, chronic high-dose opioid use, uncoordinated
      opioid use, ED visits, or rate of diagnosed opioid abuse. Relative to Arm 4, odds
      ratios (95% CI) for diagnosed opioid abuse were Arm 1, 0.95(0.63-1.42); Arm 2,
      0.83(0.55-1.27); Arm 3, 0.72(0.46-1.13). While 84.7 percent had >=1 psychiatric
      diagnoses during preindex (p = 0.89 between arms), only 9.5 percent had >=1 visit
      with mental health specialists (p = 0.53 between arms). CONCLUSIONS: Although
      this intervention did not affect pain-related outcomes, future interventions
      involving care coordination across primary care and mental health may impact
      opioid abuse and improve quality of life of patients with pain.

PMID- 29199397
TI  - Opioid tolerance and urine drug testing among initiates of extended-release or
      long-acting opioids in Food and Drug Administration's Sentinel System.
AB  - OBJECTIVE: A risk evaluation and mitigation strategy for extended-release and
      long-acting (ER/LA) opioid analgesics was approved by the Food and Drug
      Administration in 2012. Our objective was to assess frequency of opioid tolerance
      and urine drug testing for individuals initiating ER/LA opioid analgesics.
      DESIGN: Retrospective cohort study. SETTING: Sentinel, a distributed database
      with electronic healthcare data on >190 million predominantly commercially
      insured members. PATIENTS, PARTICIPANTS: Members under age 65 initiating ER/LA
      opioid analgesics between January 2009 and December 2013. MAIN OUTCOME
      MEASURE(S): We examined the proportion of opioid-tolerant-only ER/LA opioid
      analgesic initiates meeting tolerance criteria: receipt of >=30 mg oxycodone
      equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing.
      We separately examined the proportion of new users of extended-release oxycodone
      (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the
      30 days prior to, and separately for the 183 days after, dispensing. RESULTS: We
      identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778
      transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met
      in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent
      of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660
      other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared
      with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in
      the 30 days prior to initiation and 9 percent vs 23 percent respectively in the
      183 days following initiation. CONCLUSIONS: These results suggest potential areas
      for improving appropriate ER/LA opioid analgesic prescribing practices.

PMID- 29199398
TI  - Tramadol for maintenance in opioid dependence: A retrospective chart review.
AB  - BACKGROUND AND AIMS: Tramadol is an opioid agonist which can be potentially used
      for maintenance treatment of patients with opioid use disorders. This chart
      review presents the characteristics of individuals with an ICD 10 diagnosis of
      opioid dependence who were maintained on tramadol for a period of at least 6
      months. METHODS: Records of patients seeking treatment for opioid dependence from
      the outpatient clinic of the National Drug Dependence Treatment Centre,
      Ghaziabad, India were screened. One hundred consecutive patients who received
      tramadol for more than 6 months were included. RESULTS: The sample comprised
      exclusively of males and had a mean age of 40.9 years. The median dose of
      tramadol at initiation and continuation was 300 mg/day. Sixty-two patients
      achieved complete abstinence during the course of treatment. Greater age, longer
      duration of opioid use, and better follow-up adherence were associated with
      abstinent status. The rates of abstinence were higher among those presenting with
      natural opioid use as compared to others (prescription opioid use or heroin use).
      CONCLUSION: Tramadol can be an alternative medication for harm reduction in
      select group of patients with opioid dependence. Further research is required to
      strengthen the evidence base of rational use of tramadol for maintenance
      treatment of patients with opioid dependence.

PMID- 29199399
TI  - The effect of toothpicks containing flavoring and flavoring plus jambu extract
      (spilanthol) to promote salivation in patients -diagnosed with opioid-induced dry
      mouth (xerostomia).
AB  - OBJECTIVE: To determine if the use of toothpicks infused with flavoring and
      flavoring plus the food additive spilanthol (XerosticksTM) improve saliva flow in
      people with opioid-induced dry mouth. DESIGN: Time series, nonrandomized, double
      blind within-subject design. SETTING: Private practice/academic multidisciplinary
      pain and palliative care clinic. PARTICIPANTS: Ten subjects with opioid-induced
      dry mouth were recruited, and all finished the study. METHODS: Salivary flow and
      pH were measured consecutively at baseline, following use of a mango-flavored
      toothpick, and again after use of a mango-flavored toothpick infused with
      spilanthol. Salivary flow rates and saliva pH were compared between flavored and
      baseline, between flavored + spilanthol and baseline, and between the flavored
      and flavored + spilanthol. Mouthfeel of each toothpick was assessed using the
      Bluestone Mouthfeel Questionnaire. OUTCOMES: The primary measure was salivary
      flow, and the secondary measures were salivary pH and mouthfeel. RESULTS: Saliva
      flow increased 440 percent over baseline with use of a flavored toothpick and 628
      percent over baseline with similarly flavored toothpicks infused with spilanthol,
      and these differences are significant (p = 0.00002). Saliva pH increased with
      both toothpicks (p = 0.04). The addition of spilanthol produced a greater
      increase in salivary flow (p = 0.05) compared to control toothpicks with
      flavoring alone. Furthermore, addition of spilanthol improved the "mouthfeel" of
      the toothpick (p = 0.00001). CONCLUSIONS: Toothpicks infused with either
      flavoring or flavoring plus spilanthol are likely to be an effective remedy for
      opioid-induced dry mouth. Addition of spilanthol may improve effectiveness over
      flavoring alone and may be better ac-cepted because spilanthol appears to improve
      mouthfeel.

PMID- 29199401
TI  - Factors Associated with Postoperative Diabetes Insipidus after Pituitary Surgery.
AB  - BACKGROUND: Determining risk factors for diabetes insipidus (DI) after pituitary
      surgery is important in improving patient care. Our objective is to determine the
      factors associated with DI after pituitary surgery. METHODS: We reviewed records
      of patients who underwent pituitary surgery from 2011 to 2015 at Philippine
      General Hospital. Patients with preoperative DI were excluded. Multiple logistic
      regression analysis was performed and a predictive model was generated. The
      discrimination abilities of the predictive model and individual variables were
      assessed using the receiving operator characteristic curve. RESULTS: A total of
      230 patients were included. The rate of postoperative DI was 27.8%. Percent
      change in serum Na (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.15 to
      1.69); preoperative serum Na (OR, 1.19; 95% CI, 1.02 to 1.40); and performance of
      craniotomy (OR, 5.48; 95% CI, 1.60 to 18.80) remained significantly associated
      with an increased incidence of postoperative DI, while percent change in urine
      specific gravity (USG) (OR, 0.53; 95% CI, 0.33 to 0.87) and meningioma on
      histopathology (OR, 0.05; 95% CI, 0.04 to 0.70) were significantly associated
      with a decreased incidence. The predictive model generated has good diagnostic
      accuracy in predicting postoperative DI with an area under curve of 0.83.
      CONCLUSION: Greater percent change in serum Na, preoperative serum Na, and
      performance of craniotomy significantly increased the likelihood of postoperative
      DI while percent change in USG and meningioma on histopathology were
      significantly associated with a decreased incidence. The predictive model can be
      used to generate a scoring system in estimating the risk of postoperative DI.

PMID- 29199400
TI  - Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A
      Multicenter Cohort Study.
AB  - BACKGROUND: Little is known regarding disease-specific mortality of
      differentiated thyroid cancer (DTC) patients and its risk factors in Korea.
      METHODS: We retrospectively reviewed a large multi-center cohort of thyroid
      cancer from six Korean hospitals and included 8,058 DTC patients who underwent
      initial surgery between 1996 and 2005. RESULTS: Mean age of patients at diagnosis
      was 46.2+/-12.3 years; 87% were females. Most patients had papillary thyroid
      cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the
      primary tumor was 1.6+/-1.0 cm. Approximately 40% of patients had cervical lymph
      node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3
      years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year
      disease-specific survival (DSS) rate was 98%. According to the year of diagnosis,
      the number of disease-specific mortality was not different. However, the rate of
      disease-specific mortality decreased during the study period (from 7.7% to 0.7%).
      Older age (>=45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus
      PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE),
      lateral cervical LN metastasis, distant metastasis and tumor node metastasis
      (TNM) stage were independent risk factors of disease-specific mortality of DTC
      patients. CONCLUSION: The rate of disease-specific mortality of Korean DTC
      patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at
      diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN
      metastasis, distant metastasis, and TNM stages were significant risk factors of
      disease-specific mortality of Korean DTC patients.

PMID- 29199402
TI  - Changes in Body Composition According to Age and Sex among Young Non-Diabetic
      Korean Adults: The Kangbuk Samsung Health Study.
AB  - BACKGROUND: Age-related decreases in lean mass represent a serious health
      problem. We aimed to analyze the risks of rapid decreases in lean mass by age and
      sex in relatively young Korean adults during a 4-year follow-up study. METHODS: A
      total of 65,856 non-diabetic participants (59.5% men, mean age 39.1 years) in a
      health screening program were subjected to bioimpedance body composition analyses
      and metabolic parameter analyses at baseline and after 4 years. The participants
      were sub-divided according to age, and additionally to six groups by age and the
      degree of body weight change over the 4-year period. The actual changes in body
      weight, lean mass, and fat mass and the percent changes over the 4-year period
      were assessed. RESULTS: The percent change in lean mass decreased and the percent
      change of fat mass increased with increasing age in every age and sex group.
      However, the annual percent decrease in lean mass and percent increase in fat
      mass were significantly higher among women than among men (-0.26% vs. -0.15% and
      0.34% vs. 0.42%, respectively; P<0.01). Participants who were older than 50 years
      and had a weight loss <-5% during the 4 years had significantly greater decreases
      in lean mass and smaller decreases in fat mass, compared to those who were
      younger than 50 years. An odds ratio analysis to determine the lowest quartile of
      the percent change in lean mass according to age group revealed that participants
      older than 60 years had a significantly increased risk of a rapid decrease in the
      lean mass percentage (2.081; 95% confidence interval, 1.678 to 2.581).
      CONCLUSION: Even in this relatively young study population, the lean mass
      decreased significantly with age, and the risk of a rapid decrease in lean mass
      was higher among women than among men. Furthermore, the elderly exhibited a
      significantly more rapid decrease in lean mass, compared with younger
      participants.

PMID- 29199403
TI  - Prediction of Gestational Diabetes Mellitus in Pregnant Korean Women Based on
      Abdominal Subcutaneous Fat Thickness as Measured by Ultrasonography.
AB  - BACKGROUND: This study was performed to verify the correlation between abdominal
      subcutaneous fat thickness (ASFT) measured by ultrasonography (US) during the
      first trimester of pregnancy and gestational diabetes mellitus (GDM) of the
      second trimester in Korean women and to establish a standard of ASFT for
      predicting GDM. METHODS: A total of 333 singleton pregnant women participated in
      this study. Their ASFT was measured by US during the 10+6 to 13+6 weeks of
      pregnancy; then a GDM confirmatory test (100 g oral glucose tolerance test) was
      conducted during the 24 to 28 week period of pregnancy. Based on the GDM tests,
      comparative analyses of the ages of the subjects, pre-pregnancy body mass index
      (BMI), and weight gain during pregnancy were conducted. RESULTS: The ages of the
      subjects and weight gains during pregnancy were not correlated to the GDM of the
      second trimester of pregnancy, but the pre-pregnancy BMIs (22+/-3.3 kg/m2) and
      the ASFT (1.9+/-0.5 cm) measurements between the control group and subjects
      during the first trimester of pregnancy were found to show significant
      differences (P<0.001). The cut-off value of the ASFT for predicting GDM was
      determined to be 2.4 cm (area under the curve=0.90, sensitivity 75.61%,
      specificity 91.78%, P<0.001). The odds ratio was 2.91 (95% confidence interval,
      1.07 to 7.92; P=0.034), which was higher than the 2.4 cm ASFT. CONCLUSION: It was
      determined that ASFT as measured by US during the first trimester of pregnancy
      can be used to predict the risk of developing GDM during the second trimester of
      pregnancy and for prognosis.

PMID- 29199404
TI  - Improvement of Glycosylated Hemoglobin in Patients with Type 2 Diabetes Mellitus
      under Insulin Treatment by Reimbursement for Self-Monitoring of Blood Glucose.
AB  - BACKGROUND: In Korea, the costs associated with self-monitoring of blood glucose
      (SMBG) for patients with type 2 diabetes mellitus (T2DM) under insulin treatment
      have been reimbursed since November 2015. We investigated whether this new
      reimbursement program for SMBG has improved the glycemic control in the
      beneficiaries of this policy. METHODS: Among all adult T2DM patients with >=3
      months of reimbursement (n=854), subjects without any changes in anti
      hyperglycemic agents during the study period were selected. The improvement of
      glycosylated hemoglobin (HbA1c) was defined as an absolute reduction in HbA1c
      >=0.6% or an HbA1c level at follow-up <7%. RESULTS: HbA1c levels significantly
      decreased from 8.5%+/-1.3% to 8.2%+/-1.2% during the follow-up (P<0.001) in all
      the study subjects (n=409). Among them, 35.5% (n=145) showed a significant
      improvement in HbA1c. Subjects covered under the Medical Aid system showed a
      higher prevalence of improvement in HbA1c than those with medical insurance
      (52.2% vs. 33.3%, respectively, P=0.012). In the improvement group, the baseline
      HbA1c (P<0.001), fasting C-peptide (P=0.016), and daily dose of insulin/body
      weight (P=0.024) showed significant negative correlations with the degree of
      HbA1c change. Multivariate analysis showed that subjects in the Medical Aid
      system were about 2.5-fold more likely to improve in HbA1c compared to those with
      medical insurance (odds ratio, 2.459; 95% confidence interval, 1.138 to 5.314;
      P=0.022). CONCLUSION: The reimbursement for SMBG resulted in a significant
      improvement in HbA1c in T2DM subjects using insulin, which was more prominent in
      subjects with poor glucose control at baseline or covered under the Medical Aid
      system.

PMID- 29199405
TI  - Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case
      Control Study from Chungju Metabolic Disease Cohort.
AB  - BACKGROUND: Betatrophin is a newly identified hormone derived from the liver and
      adipose tissue, which has been suggested to regulate glucose and lipid
      metabolism. Circulating levels of betatrophin are altered in various metabolic
      diseases, although the results are inconsistent. We aimed to examine whether
      betatrophin is a useful biomarker in predicting the development of diabetes.
      METHODS: A nested case-control study was performed using a prospective Chungju
      Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167
      individuals who converted to diabetes and 167 non-converters, who were matched by
      age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA
      (enzyme-linked immunosorbent assay). RESULTS: Baseline serum betatrophin levels
      were significantly higher in the converter group compared to the non-converter
      group (1,315+/-598 pg/mL vs. 1,072+/-446 pg/mL, P<0.001). After adjusting for
      age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total
      cholesterol, and family history of diabetes, the risk of developing diabetes
      showed a stepwise increase across the betatrophin quartile groups. Subjects in
      the highest baseline quartile of betatrophin levels had more than a threefold
      higher risk of incident diabetes than the subjects in the lowest quartile
      (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814; P=0.010).
      However, no significant relationships were observed between serum betatrophin
      levels and indices of insulin resistance or beta-cell function. CONCLUSION:
      Circulating levels of betatrophin could be a potential biomarker for predicting
      new-onset diabetes. Further studies are needed to understand the underlying
      mechanism of this association.

PMID- 29199406
TI  - The Role of Negative Affect in the Assessment of Quality of Life among Women with
      Type 1 Diabetes Mellitus.
AB  - BACKGROUND: The purpose of this study is to determine the impact of negative
      affect (defined in terms of lack of optimism, depressogenic attributional style,
      and hopelessness depression) on the quality of life of women with type 1 diabetes
      mellitus. METHODS: Participants (n=177) completed either an online or paper
      questionnaire made available to members of Australian diabetes support groups.
      Measures of optimism, attributional style, hopelessness depression, disease
      specific data, and diabetes-related quality of life were sought. Bivariate
      correlations informed the construction of a structural equation model. RESULTS:
      Participants were 36.3+/-11.3 years old, with a disease duration of 18.4+/-11.2
      years. Age and recent glycosylated hemoglobin readings were significant
      contextual variables in the model. All bivariate associations involving the
      components of negative affect were as hypothesized. That is, poorer quality of
      life was associated with a greater depressogenic attributional style, higher
      hopelessness depression, and lower optimism. The structural equation model
      demonstrated significant direct effects of depressogenic attributional style and
      hopelessness depression on quality of life, while (lack of) optimism contributed
      to quality of life indirectly by way of these variables. CONCLUSION: The
      recognition of negative affect presentations among patients, and an understanding
      of its relevance to diabetes-related quality of life, is a valuable tool for the
      practitioner.

PMID- 29199407
TI  - Adipokines and Insulin Resistance According to Characteristics of Pregnant Women
      with Gestational Diabetes Mellitus.
AB  - BACKGROUND: The aim of this study was to evaluate adipokines concentration and
      insulin resistance according to maternal age or obesity at pregnancy and weight
      change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with
      GDM. METHODS: This study included 57 pregnant women who were diagnosed with GDM
      at 24 to 28 weeks of gestation. The subjects were classified into two or three
      groups according to pre-pregnancy body mass index (BMI, <25 kg/m2 vs. >=25
      kg/m2), maternal age at pregnancy (<35 years old vs. >=35 years old), and weight
      change during pregnancy at screening for GDM (weight change below, within, and in
      excess of the recommended range). They were respectively compared in each group.
      RESULTS: Leptin, homeostasis model assessment of insulin resistance (HOMA-IR),
      and HOMA2-%B were increased in the group with pre-pregnancy BMI >=25 kg/m2.
      Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and
      at screening for GDM. There were no significant correlations between HOMA-IR and
      adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative
      correlation with HOMA2-%S. CONCLUSION: Leptin and HOMA-IR at diagnosed GDM were
      increased in the GDM patients with obesity before pregnancy. They were positively
      correlated with BMI both before pregnancy and at screening for GDM. The effect of
      maternal age at pregnancy and weight change during pregnancy at GDM screening on
      adipokines and insulin resistance might be less pronounced than the effect of
      maternal obesity.

PMID- 29199408
TI  - Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on
      Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats.
AB  - BACKGROUND: Regular aerobic exercise is essential for the prevention and
      management of type 2 diabetes mellitus and may be particularly beneficial for
      those treated with thiazolidinediones, since it may prevent associated weight
      gain. This study aimed to evaluate the effect of combined exercise and
      rosiglitazone treatment on body composition and glucose metabolism in obese
      diabetes-prone animals. METHODS: We analyzed metabolic parameters, body
      composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after
      28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and
      rosiglitazone treatment. RESULTS: Combined exercise with rosiglitazone showed
      significantly less increase in weight and epididymal fat compared to
      rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and
      exercise treatment led to similar retention of lean body mass. All experimental
      groups showed a decrease in fasting glucose. However, the combined exercise and
      rosiglitazone therapy group showed prominent improvement in glucose tolerance
      compared to the other groups. Rescue of islet destruction was observed in all
      experimental groups, but was most prominent in the combined therapy group.
      CONCLUSION: Regular aerobic exercise combined with rosiglitazone treatment can
      compensate for the adverse effect of rosiglitazone treatment and has benefit for
      islet preservation.

PMID- 29199409
TI  - Depressive Symptoms Are Negatively Associated with Glucose Testing and Eating
      Meals on Time among Individuals with Diabetes in Zambia.
AB  - BACKGROUND: Depression is an established risk factor for cardiovascular diseases
      and mortality among individuals living with diabetes, and impaired self-care
      behaviors may play a mediating role. In Africa, this association is not very well
      known. In this study, we examined the associations between depressive symptoms
      and different aspects of diabetes self-care in Zambian individuals with diabetes
      mellitus. METHODS: A total of 157 individuals with diabetes mellitus
      participated. The sample was drawn from four city hospitals in Zambia. Diabetes
      self-care was assessed using the diabetes self-care inventory, and depression was
      assessed using the major depression inventory. RESULTS: Fifty-nine percent of the
      sample had type 1 diabetes mellitus. Variations in self-care activities and
      behaviors were reported as least adhered to by individuals with type 1 and type 2
      diabetes mellitus, in adolescent and adult patients. Regression analysis
      indicated that there was no association between total diabetes self-care and the
      depression total score. However, depression was associated with poor glucose
      testing and not eating meals on time by patients with diabetes. CONCLUSION: Some
      variance on poor self-care was explained by demographic characteristics,
      specifically age, body mass index, and to some extent, socioeconomic status.
      Recognition and successful treatment of depression in patients with diabetes
      might help to optimize self-care behaviors, especially glucose testing and eating
      meals on time. However, this hypothesis needs further testing.

PMID- 29199411
TI  - The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly
      Measured Insulin Resistance.
AB  - BACKGROUND: Plasma concentrations of some lysophospholipids correlate with
      metabolic alterations in humans, but their potential as biomarkers of insulin
      resistance (IR) is insufficiently known. We aimed to explore the association
      between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR
      in adults with different metabolic profiles. METHODS: We studied 62 men and
      women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese).
      Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which
      we calculated multiple indices of IR and insulin secretion. Fifteen participants
      additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of
      insulin-stimulated glucose disposal. Plasma LGPC was determined using high
      performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC
      was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was
      15.4+/-7.6 ng/mL in women and 14.1+/-7.3 ng/mL in men. LGPC did not correlate
      with body mass in-dex, percent body fat, waist circumference, blood pressure,
      glycosylated hemoglobin, log-triglycerides, or high density lipoprotein
      cholesterol. Plasma LGPC concentrations was not systematically associated with
      any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a
      significant negative correlation with glucose disposal in the clamp (Spearman r=
      0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC
      exhibited significantly higher post-challenge plasma glucose excursions in the 5p
      OGTT (P trend=0.021 for the increase in glucose area under the curve across
      quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without
      known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose
      metabolism.

PMID- 29199410
TI  - Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and
      Renal Diseases.
AB  - As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has
      increased, the influence of NAFLD on other metabolic diseases has been
      highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only
      affects the liver but also increases the risk of extra-hepatic diseases such as
      type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension,
      cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non
      alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter
      organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance
      and exacerbates systemic chronic inflammation and oxidative stress, which leads
      to organ dysfunction in extra-hepatic tissues. Although more research is needed
      to identify the pathophysiological mechanisms and causal relationship between
      NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and
      kidney diseases, risk assessment for diabetes, and a multidisciplinary approach
      for managing these patients should be highly encouraged.

PMID- 29199413
TI  - [Not Available].

PMID- 29199412
TI  - Evaluation of a halitosis clinic over a period of eleven years
AB  - About every fourth individual suffers at leasttemporarily from oral malodor. The
      most frequentcause of it is the oral cavity, in particular thetongue coating. In
      professional halitosis clinics,findings and diagnoses are discussed with
      thepatients, and individual therapy concepts are designed. Currently, there are
      only few ev alua- tions of such clinics, which moreover are con- fined to a
      period of a few weeks or months. The aim of the present work was to evaluate the
      halitosis clinic of the University Center of Dental Medicine Basel o ver a period
      of eleven years. For the purpose of a recall, 638 patients w ere con- tacted, who
      had visited the halitosis clinic be- tween February 2003 and February 2014. Of
      these, 280 patients answ ered a special question- naire. The halitosis clinic was
      rated as helpf ul by 81.9% of the respondents. The majority (61.8%) only rarely
      or never suffered from bad breath anymore and still carried out the recommended
      tongue cleaning. Ninety-one patients who re- ported to suffer again from oral
      malodor, could be re-evaluated also clinically. The strictly cause- oriented
      therapy concept of the halitosis clinic of the Univ ersity Center of Dental
      Medicine Basel has proved successful over eleven years.

PMID- 29199415
TI  - [Urinary tract infection by Lelliottia amnigena (Enterobacter amnigenus): an
      uncommon pathogen].

PMID- 29199414
TI  - Anti-erosive effect of a self-assembling peptide gel
AB  - This study analyzed the anti-erosive effect of a self-assembling peptide fibre
      gel. One hundred and twelve bovine enamel samples were ground flat and subjected
      to a three times de- and re-mineralization cycle: erosion (5min, HCl, pH2.6)
      alternated with storage in artificial saliva under agitation. Then, samples were
      covered with dif-ferent anti-erosive compounds (2min): Duraphat toothpaste (DT),
      Elmex Erosion Protection Tooth-paste (EET) or Elmex Gelee (EG)- all mixed with
      saliva (1:3)-, Elmex Erosion Protection Mouth-wash (EEM), Curodont Protect (CP;
      self-assem-bling peptide gel) or MI Paste Plus (MIP). Untreat-ed, water stored
      samples served as control. In experiment1, half of the samples of each group were
      continuously superfused with HCl (pH2.6, 60MUl/min, 8min). In experiment2, the
      second half of samples were subjected to eight cycles, each consisting of
      application of the respective anti-erosive compound followed by an erosion (60s,
      HCl, pH2.6), followed by remineralization in artificial saliva (45min). Enamel
      loss was profi-lometrically determined.In experiment1, EEM and EET performed
      signifi-cantly better compared to all other compounds. Substance loss of all
      other compounds did not differ significantly from control. In experiment2,
      significantly better performance was achieved by EEM and EET. EG showed
      significantly lower pro-tection than the control. All other applied com-pounds
      yielded no significant difference com-pared to control.Under the chosen
      conditions, the self-assembling peptide-containing compound showed no anti
      erosive effect.

PMID- 29199416
TI  - [IgG4 seroconversion in a patient with chronic brucellosis with biliary focus].

PMID- 29199417
TI  - [Pulmonary mucormycosis due to Cunninghamella spp. in renal transplant patient].

PMID- 29199418
TI  - [Cefditoren: a reality for the treatment of community infections].
AB  - Cefditoren, a third-generation cephalosporin, is the oral beta-lactam more active
      against the main community-acquired respiratory tract pathogens (including
      resistance phenotypes such as penicillin-resistant Streptococcus pneumoniae and
      ampicillin-resistant Haemophilus influenzae), similar to cefotaxime. Data
      obtained from clinical trials and later evidence on efficacy and safety, support
      that cefditoren is an suitable option for the treatment of mild-to moderate
      community respiratory and urinary tract infections, particularly in regions where
      non-susceptible phenotipes to common oral antibiotics are prevalent.

PMID- 29199419
TI  - [Not Available].

PMID- 29199420
TI  - [Not Available].

PMID- 29199421
TI  - Novel Electrosorption-Enhanced Solid-Phase Microextraction Device for Ultrafast
      In Vivo Sampling of Ionized Pharmaceuticals in Fish.
AB  - Decreasing the tedious sample preparation duration is one of the most important
      concerns for the environmental analytical chemistry especially for in vivo
      experiments. However, due to the slow mass diffusion paths for most of the
      conventional methods, ultrafast in vivo sampling remains challenging. Herein, for
      the first time, we report an ultrafast in vivo solid-phase microextraction (SPME)
      device based on electrosorption enhancement and a novel custom-made CNT@PPY@pNE
      fiber for in vivo sampling of ionized acidic pharmaceuticals in fish. This
      sampling device exhibited an excellent robustness, reproducibility, matrix effect
      resistant capacity, and quantitative ability. Importantly, the extraction
      kinetics of the targeted ionized pharmaceuticals were significantly accelerated
      using the device, which significantly improved the sensitivity of the SPME in
      vivo sampling method (limits of detection ranged from 0.12 ng.g-1 to 0.25 ng.g-1)
      and shorten the sampling time (only 1 min). The proposed approach was
      successfully applied to monitor the concentrations of ionized pharmaceuticals in
      living fish, which demonstrated that the device and fiber were suitable for
      ultrafast in vivo sampling and continuous monitoring. In addition, the
      bioconcentration factor (BCF) values of the pharmaceuticals were derived in
      tilapia (Oreochromis mossambicus) for the first time, based on the data of
      ultrafast in vivo sampling. Therefore, we developed and validated an effective
      and ultrafast SPME sampling device for in vivo sampling of ionized analytes in
      living organisms and this state-of-the-art method provides an alternative
      technique for future in vivo studies.

PMID- 29199422
TI  - "Double-Cable" Conjugated Polymers with Linear Backbone toward High Quantum
      Efficiencies in Single-Component Polymer Solar Cells.
AB  - A series of "double-cable" conjugated polymers were developed for application in
      efficient single-component polymer solar cells, in which high quantum
      efficiencies could be achieved due to the optimized nanophase separation between
      donor and acceptor parts. The new double-cable polymers contain electron-donating
      poly(benzodithiophene) (BDT) as linear conjugated backbone for hole transport and
      pendant electron-deficient perylene bisimide (PBI) units for electron transport,
      connected via a dodecyl linker. Sulfur and fluorine substituents were introduced
      to tune the energy levels and crystallinity of the conjugated polymers. The
      double-cable polymers adopt a "face-on" orientation in which the conjugated BDT
      backbone and the pendant PBI units have a preferential pi-pi stacking direction
      perpendicular to the substrate, favorable for interchain charge transport normal
      to the plane. The linear conjugated backbone acts as a scaffold for the
      crystallization of the PBI groups, to provide a double-cable nanophase separation
      of donor and acceptor phases. The optimized nanophase separation enables
      efficient exciton dissociation as well as charge transport as evidenced from the
      high-up to 80%-internal quantum efficiency for photon-to-electron conversion. In
      single-component organic solar cells, the double-cable polymers provide power
      conversion efficiency up to 4.18%. This is one of the highest performances in
      single-component organic solar cells. The nanophase-separated design can likely
      be used to achieve high-performance single-component organic solar cells.

PMID- 29199423
TI  - Effect of Dielectric Interface on the Performance of MoS2 Transistors.
AB  - Because of their wide bandgap and ultrathin body properties, two-dimensional
      materials are currently being pursued for next-generation electronic and
      optoelectronic applications. Although there have been increasing numbers of
      studies on improving the performance of MoS2 field-effect transistors (FETs)
      using various methods, the dielectric interface, which plays a decisive role in
      determining the mobility, interface traps, and thermal transport of MoS2 FETs,
      has not been well explored and understood. In this article, we present a
      comprehensive experimental study on the effect of high-k dielectrics on the
      performance of few-layer MoS2 FETs from 300 to 4.3 K. Results show that
      Al2O3/HfO2 could boost the mobility and drain current. Meanwhile, MoS2
      transistors with Al2O3/HfO2 demonstrate a 2* reduction in oxide trap density
      compared to that of the devices with the conventional SiO2 substrate. Also, we
      observe a negative differential resistance effect on the device with 1 MUm
      channel length when using conventional SiO2 as the gate dielectric due to self
      heating, and this is effectively eliminated by using the Al2O3/HfO2 gate
      dielectric. This dielectric engineering provides a highly viable route to
      realizing high-performance transition metal dichalcogenide-based FETs.

PMID- 29199424
TI  - Preparation of Novel Fluorescent Nanocomposites Based on Au Nanoclusters and
      Their Application in Targeted Detection of Cancer Cells.
AB  - Fluorescent gold nanoclusters (AuNCs) have drawn considerable research interest
      owing to their unique emission properties. However, the environment surrounding
      the NC greatly influences its luminous behavior. In this work, a novel
      nanocomposite based on AuNCs with bright fluorescence and high biocompatibility
      was prepared. In this nanocomposite, mesoporous silica nanospheres provided a
      mesoporous framework, which helped to template the formation of ultrasmall AuNCs
      and also prevented their aggregation in different solutions. These nanocomposites
      emitted stable fluorescence even in complex biological environments. After the
      self-assembly of folic acid-conjugated poly(l-lysine), the presence of folic acid
      on the nanocomposites guaranteed a good recognition in folate receptor (FR)
      positive cells, improving detection selectivity. Cellular experiments
      demonstrated that the nanocomposites had good dispersity in the physiological
      environment and could be internalized by FR-positive cancer cells, resulting in
      bright fluorescence. We believe that this research provides a simple approach to
      the fabrication of stable fluorescent AuNC nanocomposites, which show good
      compatibility with complex biological systems and great potential for
      applications in biological imaging and cell detection.

PMID- 29199425
TI  - Piecemeal Rekindling of Coumarin 6 Fluorescence on Stepwise Unfolding of Protein
      by Surfactant.
AB  - Coumarin 6 (C6) briskly aggregates in water, and as a result, rapidly loses
      fluorescence. However, vicinal hydrophobic cavity can induce disintegration of
      the aggregates, and thus reviving the fluorescence. It is shown that carrier
      protein, such as bovine serum albumin (BSA), can disintegrate the microcrystals
      of C6 to smaller fragments and trap them inside the hydrophobic domain of the
      folded protein. This results into a 12-fold enhancement in the fluorescence
      signal of C6. However, on unfolding BSA by micelles, the C6 microcrystals break
      into single molecules by getting trapped in the micelles, and hence emission
      enhances by more than 100-folds.

PMID- 29199426
TI  - Characterization of Key Factors of Anchovy (Engraulis japonicus) Meat in the
      Nanoparticle-Mediated Enhancement of Non-Heme Iron Absorption.
AB  - Anchovy (Engraulis japonicus) meat (AM) has been shown to promote nonheme iron
      absorption via a ferric oxyhydroxide nanoparticle (FeONP)-mediated mechanism.
      Here, formulation modifications of an egg-white-based AIN-93G diet with AM
      fractions resulted hemoglobin regeneration efficiencies in anemic rats following
      an order control (23.69 +/- 3.99%) < ferrous-sulfate-replacement of ferric
      citrate (39.89 +/- 2.97%) ~ dehemeed-AM-protein-replacement of egg white (45.88
      +/- 4.76%) ~ AM-lipid-replacement of soybean oil (43.14 +/- 3.48%) ~ chondroitin
      sulfate-replacement of ~2.5% corn starch (39.92 +/- 1.88%) < l-alpha
      phosphatidylcholine-replacement of ~29% soybean oil (53.42 +/- 2.04%), with
      nanosized iron enriched in proximal-small-intestinal contents by these AM
      fractions. The calcein-fluorescence-quenching assay in polarized Caco-2 cells
      revealed good iron absorption from FeONPs coated with AM peptides, l-alpha
      phosphatidylcholine, l-alpha-lysophosphatidylcholine, and chondroitin sulfate,
      with the latter two disfavoring endocytosis thereby inducing relatively weaker
      iron absorption. These results suggest peptides, phospholipids, and
      mucopolysaccharides released during AM digestion are key factors promoting
      nonheme iron absorption.

PMID- 29199427
TI  - Predictive value of routine point-of-care cardiac troponin T measurement for
      prehospital diagnosis and risk-stratification in patients with suspected acute
      myocardial infarction.
AB  - OBJECTIVE: The purpose of this study was to determine the predictive value of
      routine prehospital point-of-care cardiac troponin T measurement for diagnosis
      and risk stratification of patients with suspected acute myocardial infarction.
      METHODS AND RESULTS: All prehospital emergency medical service vehicles in the
      Central Denmark Region were equipped with a point-of-care cardiac troponin T
      device (Roche Cobas h232) for routine use in all patients with a suspected acute
      myocardial infarction. During the study period, 1 June 2012-30 November 2015,
      prehospital point-of-care cardiac troponin T measurements were performed in a
      total of 19,615 cases seen by the emergency medical service and 18,712 point-of
      care cardiac troponin T measurements in 15,781 individuals were matched with an
      admission. A final diagnosis of acute myocardial infarction was confirmed in 2187
      cases and a total of 2150 point-of-care cardiac troponin T measurements (11.0%)
      had a value >=50 ng/l, including 966 with acute myocardial infarction
      (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital
      point-of-care cardiac troponin T value >=50 ng/l had a one-year mortality of 24%
      compared with 4.8% in those with values <50 ng/l, log-rank: p<0.001. The
      following variables showed the strongest association with mortality in
      multivariable analysis: point-of-care cardiac troponin T>=50 ng/l (hazard ratio
      2.10, 95% confidence interval: 1.90-2.33), congestive heart failure (hazard ratio
      1.93, 95% confidence interval: 1.74-2.14), diabetes mellitus (hazard ratio 1.42,
      95% confidence interval: 1.27-1.59) and age, one-year increase (hazard ratio
      1.08, 95% confidence interval: 1.08-1.09). CONCLUSIONS: Patients with suspected
      acute myocardial infarction and a prehospital point-of-care cardiac troponin T
      >=50 ng/l have a poor prognosis irrespective of the final diagnosis. Routine
      troponin measurement in the prehospital setting has a high predictive value and
      can be used to identify high-risk patients even before hospital arrival so that
      they may be re-routed directly for advanced care at an invasive centre.

PMID- 29199428
TI  - Cluster headache and middle meningeal artery dural arteriovenous fistulas: A case
      report.
AB  - Background Of the multiple etiologies identified for symptomatic cluster
      headache, vascular origin is common; however, there are no known reports of
      arteriovenous (AV) fistulas. Here we report a case with typical presentation of
      cluster headache, which might be associated with middle meningeal AV fistulas.
      Case report The subject is a 49-year-old man with a 7-year history of episodic
      left-side cluster headache, consistent with the criteria in the International
      Classification of Headache Disorders, 3rd edition, beta version (ICHD-3beta).
      Magnetic resonance angiography (MRA) demonstrated dural arteriovenous fistulas at
      the left posterior fossa, which is supplied mainly by the left middle meningeal
      artery. After endovascular balloon-assisted embolization, his symptoms have
      disappeared without relapse for 1.5 years. Discussion We suggest that middle
      meningeal arteriovenous fistulas should be considered as a potential differential
      diagnosis of secondary cluster headache, even when the initial clinical
      manifestations and treatment response are typical for primary cluster headache.

PMID- 29199429
TI  - Reply to the letter by Min et al.

PMID- 29199431
TI  - Six-month clinical course and factors associated with non-improvement in migraine
      and non-migraine headaches.
AB  - Background Evidence on the medium-term clinical course of recurrent headaches is
      scarce. This study explored the six-month course and factors associated with non
      improvement in migraine compared with tension-type headache and cervicogenic
      headache. Methods In this longitudinal cohort study, the six-month course of
      headaches was prospectively examined in participants (n = 37 with migraine; n =
      42 with tension-type or cervicogenic headache). Participants underwent physical
      examination for cervical musculoskeletal impairments at baseline. Participants
      also completed questionnaires on pain, disability and other self-report measures
      at baseline and follow-up, and kept an electronic diary for 6 months. Course of
      headaches was examined using mixed within-between analyses of variance and Markov
      chain modeling. Multiple factors were evaluated as possible factors associated
      with non-improvement using regression analysis. Results Headache frequency,
      intensity, and activity interference in migraine and non-migraine headaches were
      generally stable over 6 months but showed month-to-month variations. Day-to-day
      variations were more volatile in the migraine than the non-migraine group, with
      the highest probability of transitioning from any headache state to no headache
      (probability = 0.82-0.85). The odds of non-improvement in disability was nearly
      six times higher with cervical joint dysfunction (odds ratio [95% CI] = 5.58
      [1.14-27.42]). Conclusions Headache frequency, intensity, and activity
      interference change over 6 months, with day-to-day variation being more volatile
      in migraine than non-migraine headaches. Cervical joint dysfunction appears to be
      associated with non-improvement for disability in 6 months. These results may
      contribute to strategies for educating patients to help align their expectations
      with the nature of their headaches.

PMID- 29199433
TI  - A Systematic Review of Parent-Implemented Functional Communication Training for
      Children With ASD.
AB  - Supporting parents in reducing challenging behavior of children with autism
      spectrum disorder (ASD) requires the identification of effective, feasible, and
      sustainable interventions. Functional communication training (FCT) is one of the
      most well-established interventions in the behavioral literature and is used
      increasingly by parents. However, there is a need for additional evaluation of
      the literature related to parent-implemented FCT. In the present review, we
      identified 26 peer-reviewed studies on parent-implemented FCT. We conducted
      systematic descriptive and social validity analyses to summarize the extant
      literature. Across studies, parent-implemented FCT was effective in reducing
      child challenging behavior, and in some cases, intervention outcomes maintained
      and generalized to novel settings and implementers. However, few studies reported
      fidelity data on parent implementation of FCT, and data regarding sustained use
      of FCT by parents were limited. Results of the social validity analysis indicate
      that while FCT is often implemented by natural change agents in typical settings,
      parent training is often provided by professionals not typically accessible to
      parents. These findings suggest that future research is warranted in the areas of
      parent training and long-term sustainability of parent-implemented FCT.

PMID- 29199432
TI  - Whey protein concentrate supplementation protects rat brain against aging-induced
      oxidative stress and neurodegeneration.
AB  - Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids
      and is consumed as a functional food, incorporating a wide range of nutritional
      attributes. The purpose of this study is to evaluate the neuroprotective effect
      of WPC on rat brain during aging. Young (4 months) and old (24 months) male
      Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days.
      Biomarkers of oxidative stress and antioxidant capacity in terms of ferric
      reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T
      SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and
      acetylcholinesterase (AChE) activity were measured in brain of control and
      experimental (WPC supplemented) groups. In addition, gene expression and
      histopathological studies were also performed. The results indicate that WPC
      augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old
      control. Furthermore, WPC-treated groups exhibited significant reduction in LHP,
      PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the
      expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)
      1beta, IL-6), and upregulated the expression of marker genes associated with
      autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase,
      Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional
      nutritional food supplement that prevents the progression of age-related
      oxidative damage in Wistar rats.

PMID- 29199434
TI  - A single centre prospective cohort study addressing the effect of a rule-in/rule
      out troponin algorithm on routine clinical practice.
AB  - AIMS: In 2015, the European Society of Cardiology introduced new guidelines for
      the diagnosis of acute coronary syndromes in patients presenting without
      persistent ST-segment elevation. These guidelines included the use of high
      sensitivity troponin assays for 'rule-in' and 'rule-out' of acute myocardial
      injury at presentation (using a '0 hour' blood test). Whilst these algorithms
      have been extensively validated in prospective diagnostic studies, the outcome of
      their implementation in routine clinical practice has not been described. The
      present study describes the change in the patient journey resulting from
      implementation of such an algorithm in a busy innercity Emergency Department.
      METHODS AND RESULTS: Data were prospectively collected from electronic records at
      a large Central London hospital over seven months spanning the periods before,
      during and after the introduction of a new high-sensitivity troponin rapid
      diagnostic algorithm modelled on the European Society of Cardiology guideline.
      Over 213 days, 4644 patients had high-sensitivity troponin T measured in the
      Emergency Department. Of these patients, 40.4% could be 'ruled-out' based on the
      high-sensitivity troponin T concentration at presentation, whilst 7.6% could be
      'ruled-in'. Adoption of the algorithm into clinical practice was associated with
      a 37.5% increase of repeat high-sensitivity troponin T measurements within 1.5 h
      for those patients classified as 'intermediate risk' on presentation.
      CONCLUSIONS: Introduction of a 0 hour 'rule-in' and 'rule-out' algorithm in
      routine clinical practice enables rapid triage of 48% of patients, and is
      associated with more rapid repeat testing in intermediate risk patients.

PMID- 29199435
TI  - [Laboratory aspects of novel oral anticoagulant treatment].
AB  - The introduction of novel oral anticoagulants (NOAC) have long been expected
      drugs and they quickly became used widespread as their clinical effectiveness was
      as good as, or even better than the previously used only oral anticoagulant drug,
      the coumarins. Thus, the direct thrombin inhibitor dabigatran and the activated
      factor X inhibitors (rivaroxaban, apixaban, edoxaban) have become the part of
      daily therapeutic practice. Their permeation was facilitated by the guideline
      which suggested that no laboratory monitoring was required during NOAC treatment
      and this was very convenient for both patients and doctors. The clinical
      experience obtained in the past years, however have proved that the 'one size
      fits all' view is oversimplified and there are numerous situations when the
      determination NOAC levels is unavoidable or highly recommended. This review
      discusses the laboratory aspects of NOAC treatment, primarily summarizing their
      effect on the screening tests and special assays of hemostasis and we also
      describe the correct methods to determine their plasma concentrations. Orv Hetil.
      2017; 158(49): 1930-1945.

PMID- 29199436
TI  - [Considerations on the treatment of IgA nephropathy on the basis of the results
      of the latest studies (STOP-IgAN, TESTING, NEFIGAN)].
AB  - IgA nephropathy is an immune-mediated chronic glomerulonephritis with a great
      variability in clinical presentation and outcome. The disease can progress to end
      stage renal failure in 25% of patients. For this reason we should identify
      patients with potential to progress. Most important risk factors for progression
      are persistent proteinuria, hypertension, decreased renal function and some
      histological lesions. The actually suggested treatment is summarized in KDIGO
      Clinical Practice Guideline from 2012. They suggest to give firstly non-specific
      supportive treatment (especially renin-angiotensin system blocking agents).
      Recommendation about steroid/immunosuppression treatment is based on low level of
      evidence. Recently three studies were organised concerning benefits and risk of
      steroid/immunosuppressive treatment added together with specific supportive
      treatment. In the STOP-IgAN study, systemic steroid/immunosuppressive treatment
      significantly decreased proteinuria but did not stop progression. In the TESTING
      study, systemic steroid treatment significantly decreased proteinuria and
      progression. However, the study was recently discontinued due to several severe
      side effects of steroid treatment. Involvement of intestinal mucosal immunity in
      the pathogenesis of IgA nephropathy suggested the NEFIGAN study with budesonide
      treatment. Budesonide releases corticosteroid in distal small intestine and
      colon. Proteinuria was significantly decreased and renal function remained
      stabile. High number of withdrawals owing to adverse effects is a major concern
      implying a substantial systemic effect of budesonide. We need further information
      on the characteristics of patients who most likely benefit from
      steroid/immunosuppressive treatment given after or together with specific
      supportive treatment. Orv Hetil. 2017; 158(49): 1946-1952.

PMID- 29199437
TI  - [Safety data of the new, reduced-dose influenza vaccine FluArt after its first
      season on the market].
AB  - INTRODUCTION: The currently licensed seasonal influenza vaccines contain split,
      subunit or whole virions, typically in amounts of 15 ug hemagglutinin per virus
      strain for adult and up to 60 ug in elderly patients. AIM: The present study
      reports safety data of the newly licensed, reduced dose vaccine with 6 ug of
      hemagglutinin per strain produced by Fluart (Hungary) after its first season on
      the market. The main objective of enhanced safety surveillance was to detect a
      potential increase in reactogenicity and allergic events that is intrinsic to the
      product in near real-time in the earliest vaccinated cohorts. METHOD: The study
      methods were based on the Interim guidance on enhanced safety surveillance for
      seasonal influenza vaccines in the EU by the European Medicines Agency.
      STATISTICS: We used the Fisher exact test with 95% confidence intervals. RESULTS:
      We studied 587 patients and detected a total 24 adverse events, all of which have
      already been known during the licensing studies of the present vaccine. The
      frequencies of the adverse events were not different from what had been seen with
      the previously licensed 15 ug vaccine. CONCLUSIONS: Based on the results, the
      authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable.
      Orv Hetil. 2017; 158(49): 1953-1959.

PMID- 29199438
TI  - [Dr. Jozsef Gelencser (1930-2017)].

PMID- 29199439
TI  - [Motivation for weight loss among weight loss treatment participants].
AB  - INTRODUCTION: Unrealistic expectations about weight goal and about weight loss
      related benefits can hinder the effort for a successful long-term weight control.
      AIM: To explore weight loss-related goals and their background among
      overweight/obese patients. METHOD: Study sample consisted of patients who
      participated in the inpatient weight loss treatment in the Lipidological
      Department of Szent Imre Hospital (n = 339, 19% men). Mean age: 50.2 years (SD =
      13.47 years), mean BMI: 38.6 (SD = 7.58). MEASURES: self-reported anthropometric
      data, type and number of treated illnesses, Goals and Relative Weights
      Questionnaire, Motivations for Weight Loss Scale, Body Shape Questionnaire.
      RESULTS: Participants would feel disappointed with a possible 10% weight loss in
      a half-year time span. The acceptable weight loss percentage was higher among
      women, younger participants and among those who had more excess weight.
      Motivation regarding the increase in social desirability by weight loss is in
      association with body dissatisfaction, health related motivation is in
      association with the number of treated illnesses. CONCLUSIONS: Our results are
      contributing to the understanding of motivational factors behind weight reduction
      efforts, considering these can improve treatment success rates. Orv Hetil. 2017;
      158(49): 1960-1967.

PMID- 29199440
TI  - A study of high-, middle- and low-molecular weight adiponectin in urine as a
      surrogate marker for early diabetic nephropathy using ultrasensitive immune
      complex transfer enzyme immunoassay.
AB  - Background For the early identification of patients at risk of developing
      diabetic nephropathy, we have developed an ultrasensitive immune complex transfer
      enzyme immunoassay to measure adiponectin in urine. Methods We developed immune
      complex transfer enzyme immunoassay for adiponectin and measured urinary
      adiponectin from 70 healthy subjects, 35 obese non-diabetic subjects and 20
      patients with diabetes. Results The urinary adiponectin concentrations in
      patients with diabetes (3.3 +/- 10.7 ng/mg creatinine) were significantly higher
      than those in obese subjects (0.54 +/- 0.44; P < 0.01) and healthy subjects (0.46
      +/- 0.42; P < 0.001). The gel filtration elution profile of urine from healthy
      subjects showed traces of four immunoreactive peaks (high-, medium-, low
      molecular weight and monomer molecules), despite the majority of blood
      adiponectin being high-molecular weight. However, urinary adiponectin molecules
      were more frequent in low-molecular weight as the estimate glomerular filtration
      rate decreased. Furthermore, as blood glucose concentrations rose, middle
      molecular weight and high-molecular weight increased in urine. Further, urinary
      adiponectin concentrations correlated with estimate glomerular filtration rate (
      r = -0.61, P < 0.001), but not urinary albumin. In addition, our analysis showed
      a significantly ( P < 0.001) higher value for urinary adiponectin in the G2 stage
      of chronic kidney disease classification where urinary albumin is not elevated.
      Conclusion Adiponectin increases in urine as renal function decreases, and
      urinary adiponectin may be useful as a surrogate marker for diabetic nephropathy
      risk.

PMID- 29199441
TI  - The effectiveness of a routine versus an extensive laboratory analysis in the
      diagnosis of anaemia in general practice.
AB  - Background We investigated the percentage of patients diagnosed with the correct
      underlying cause of anaemia by general practitioners when using an extensive
      versus a routine laboratory work-up. Methods An online survey was distributed
      among 836 general practitioners. The survey consisted of six cases, selected from
      an existing cohort of anaemia patients ( n = 3325). In three cases, general
      practitioners were asked to select the laboratory tests for further diagnostic
      examination from a list of 14 parameters (i.e. routine work-up). In the other
      three cases, general practitioners were presented with all 14 laboratory test
      results available (i.e. extensive work-up). General practitioners were asked to
      determine the underlying cause of anaemia in all six cases based on the test
      results, and these answers were compared with the answers of an expert panel.
      Results A total of 139 general practitioners (partly) responded to the survey
      (17%). The general practitioners were able to determine the underlying cause of
      anaemia in 53% of cases based on the routine work-up, whereas 62% of cases could
      be diagnosed using an extensive work-up ( P = 0.007). In addition, the
      probability of a correct diagnosis decreased with the patient's age and was also
      affected by the underlying cause itself, with anaemia of chronic disease being
      hardest to diagnose ( P = 0.003). Conclusion The use of an extensive laboratory
      work-up in patients with newly diagnosed anaemia is expected to increase the
      percentage of correct underlying causes established by general practitioners.
      Since the underlying cause can still not be established in 31.3% of anaemia
      patients, further research is necessary.

PMID- 29199442
TI  - Assessing the cost-effectiveness of a routine versus an extensive laboratory work
      up in the diagnosis of anaemia in Dutch general practice.
AB  - Background Establishing the underlying cause of anaemia in general practice is a
      diagnostic challenge. Currently, general practitioners individually determine
      which laboratory tests to request (routine work-up) in order to diagnose the
      underlying cause. However, an extensive work-up (consisting of 14 tests)
      increases the proportion of patients correctly diagnosed. This study investigates
      the cost-effectiveness of this extensive work-up. Methods A decision-analytic
      model was developed, incorporating all societal costs from the moment a patient
      presents to a general practitioner with symptoms suggestive of anaemia (aged >=
      50 years), until the patient was (correctly) diagnosed and treated in primary
      care, or referred to (and diagnosed in) secondary care. Model inputs were derived
      from an online survey among general practitioners, expert estimates and published
      data. The primary outcome measure was expressed as incremental cost per
      additional patient diagnosed with the correct underlying cause of anaemia in
      either work-up. Results The probability of general practitioners diagnosing the
      correct underlying cause increased from 49.6% (95% CI: 44.8% to 54.5%) in the
      routine work-up to 56.0% (95% CI: 51.2% to 60.8%) in the extensive work-up (i.e.
      +6.4% [95% CI: -0.6% to 13.1%]). Costs are expected to increase slightly from
      ?842/patient (95% CI: ?704 to ?994) to ?845/patient (95% CI: ?711 to ?994), i.e.
      +?3/patient (95% CI: ?-35 to ?40) in the extensive work-up, indicating
      incremental costs of ?43 per additional patient correctly diagnosed. Conclusions
      The extensive laboratory work-up is more effective for diagnosing the underlying
      cause of anaemia by general practitioners, at a minimal increase in costs. As
      accompanying benefits in terms of quality of life and reduced productivity losses
      could not be captured in this analysis, the extensive work-up is likely cost
      effective.

PMID- 29199443
TI  - Successful Prediction of a Left Nonrecurrent Laryngeal Nerve in a Patient With
      Right-Sided Aorta and Aberrant Left Subclavian Artery.
AB  - BACKGROUND: Left nonrecurrent laryngeal nerve (LNRLN) is an extremely rare
      anatomic variant. The development of such anatomic variation requires the
      regression of both the fourth (aortic arch) and sixth (ductus arteriosus, DA)
      arches on the left side. Preoperative prediction of this variant is difficult but
      might reduce risk of nerve injury. METHODS: A 34-year-old female was indicated
      for thyroidectomy for a 2.4 cm follicular neoplasm and Graves' disease. Due to a
      positive medical history of 22q11.2 microdeletion and unexplained left vocal cord
      paralysis, a preoperative chest computed tomography (CT) scan was obtained and
      revealed a right-sided aorta (RSA) and aberrant left subclavian artery (ALSA)
      without Kommerell's diverticulum. A left-sided NRLN was then highly suspected.
      RESULTS: Thyroidectomy was performed under general anesthesia with the
      utilization of intraoperative laryngeal nerve monitoring. A LNRLN was confirmed
      intraoperatively. CONCLUSIONS: Right-sided aorta and ALSA indicate embryologic
      regression of the left fourth primitive aortic arch. The absence of Kommerell's
      diverticulum at the origin of the ALSA indicates the lack of high-pressure blood
      flow from the pulmonary artery to the ALSA through the ductus arteriosus during
      embryogenesis, suggesting the embryologic regression of the left sixth primitive
      aortic arch. The presence of all 3 radiologic features thus highly suggests the
      possibility of a LNRLN.

PMID- 29199444
TI  - Steering Sheath for 2-Nostril Transnasal Office Laryngoscopy.
AB  - OBJECTIVE: The aim was to study the feasibility of performing office-based
      laryngeal procedures employing a flexible hollow steerable sheath placed
      contralateral to the nostril through which a standard flexible video endoscope is
      placed. METHODS: The study design included simulation of transnasal endoscopic
      laryngeal procedures evaluating the use of a flexible steering sheath in
      laboratory and clinic settings. Transnasal laryngeal procedures were performed in
      an otolaryngology office setting employing an airway-management-trainer mannequin
      and then repeated in a human cadaver lab with standard transnasal flexible video
      laryngoscopy. Video documentation assessed use of a lever-manipulated deflecting
      ureteral access sheath with an inner diameter of 2.97 mm, an outer diameter of
      4.95 mm, and a length of 45 cm. Simulated transnasal laryngoscopy procedures
      deployed devices through the deflecting sheath to mimic vocal fold needle
      injection, biopsy with forceps, balloon dilation, and laser treatment to identify
      strengths and shortcomings to the technology and technique. RESULTS: Simulation
      was successful in appropriately directing instrumentation for all procedures
      tested. Shortcomings included limitations in steering capacity, greater length to
      the sheath than desirable for laryngeal procedures, and the need for additional
      assistants to perform procedures. CONCLUSION: Steering sheath technology is
      applicable to enhance in-office transnasal laryngoscopy procedures.

PMID- 29199445
TI  - Analysis of the Auditory Feedback and Phonation in Normal Voices.
AB  - PURPOSE: The aim of this study was to investigate the auditory feedback
      mechanisms and voice quality during phonation in response to a spontaneous pitch
      change in the auditory feedback. Does the pitch shift reflex (PSR) change voice
      pitch and voice quality? Quantitative and qualitative voice characteristics were
      analyzed during the PSR. METHOD: Twenty-eight healthy subjects underwent
      transnasal high-speed video endoscopy (HSV) at 8000 fps during sustained
      phonation [a]. While phonating, the subjects heard their sound pitched up for 700
      cents (interval of a fifth), lasting 300 milliseconds in their auditory feedback.
      The electroencephalography (EEG), acoustic voice signal, electroglottography
      (EGG), and high-speed-videoendoscopy (HSV) were analyzed to compare feedback
      mechanisms for the pitched and unpitched condition of the phonation paradigm
      statistically. Furthermore, quantitative and qualitative voice characteristics
      were analyzed. RESULTS: The PSR was successfully detected within all signals of
      the experimental tools (EEG, EGG, acoustic voice signal, HSV). A significant
      increase of the perturbation measures and an increase of the values of the
      acoustic parameters during the PSR were observed, especially for the audio
      signal. CONCLUSIONS: The auditory feedback mechanism seems not only to control
      for voice pitch but also for voice quality aspects.

PMID- 29199446
TI  - Advances in School-Based Interventions for Students With Autism Spectrum
      Disorder: Introduction to the Special Issue.
AB  - As the diagnosis of autism spectrum disorder has increased, so too has research
      on interventions to address core and associated features of autism. Although many
      methodologically rigorous studies on interventions have been reported, their
      relevance to educators is somewaht unclear. For example, only about 32% of
      evidence-based strategies identifed in these reviews were conducted in k-12
      settings. Current literature also is limited in that, although many studies show
      that interventions can improve the communication and social interaction skills of
      individuals with autism, most of this work has been conducted with pre-school
      children; questions remain about the generality of these findings to school-aged
      children. Further, there are relatively few studies demonstrating effective
      interventions for restricted and repetitive behavior and much of this work was
      conducted in clinical settings. There is a need for studies documenting effective
      interventions that are feasible in school settings. The purpose of this special
      issue is two-fold. First, to highlight the need for school-based research with
      students with autism and second to highlight recent work delineating intervention
      strategies found to be effective in school settings.

PMID- 29199447
TI  - Selection and Implementation of Skill Acquisition Programs by Special Education
      Teachers and Staff for Students With Autism Spectrum Disorder.
AB  - The present investigation examined special education teachers' selection and use
      of teaching strategies for receptive identification training with children with
      autism spectrum disorder (ASD) in their classrooms. Teachers first responded to a
      survey in which they provided examples of receptive identification tasks taught
      in their classrooms, rated the efficacy of teaching strategies, described how
      they determined whether skills were mastered, listed any assessments they
      conducted to identify relevant prerequisite skills prior to receptive
      identification training, described how they selected teaching strategies for use
      in their classrooms, and listed their years of experience as a teacher and
      working with children with ASD. Subsequent observations of implementation of
      teaching strategies during trial-based instruction occurred in a proportion of
      teachers' classrooms. The results of the observations showed that participants
      did not consistently implement components of trial-based instruction as described
      in the literature, and there were differences in implementation depending on the
      types of skills targeted during instruction.

PMID- 29199448
TI  - Exploring the Moderating Effects of Cognitive Abilities on Social Competence
      Intervention Outcomes.
AB  - Many populations served by special education, including those identified with
      autism, emotional impairments, or students identified as not ready to learn,
      experience social competence deficits. The Social Competence Intervention
      Adolescents' (SCI-A) methods, content, and materials were designed to be
      maximally pertinent and applicable to the social competence needs of early
      adolescents (i.e., age 11-14 years) identified as having scholastic potential but
      experiencing significant social competence deficits. Given the importance of
      establishing intervention efficacy, the current paper highlights the results from
      a four-year cluster randomized trial (CRT) to examine the efficacy of SCI-A (n =
      146 students) relative to Business As Usual (n = 123 students) school-based
      programming. Educational personnel delivered all programming including both
      intervention and BAU conditions. Student functioning was assessed across multiple
      time points, including pre-, mid-, and post-intervention. Outcomes of interest
      included social competence behaviors, which were assessed via both systematic
      direct observation and teacher behavior rating scales. Data were analyzed using
      multilevel models, with students nested within schools. Results suggested after
      controlling for baseline behavior and student IQ, BAU and SCI students differed
      to a statistically significant degree across multiple indicators of social
      performance. Further consideration of standardized mean difference effect sizes
      revealed these between-group differences to be representative of medium effects
      (d > .50). Such outcomes pertained to student (a) awareness of social cues and
      information, and (b) capacity to appropriately interact with teachers and peers.
      The need for additional power and the investigation of potential moderators and
      mediators of social competence effectiveness are explored.

PMID- 29199449
TI  - Structure, conformation in aqueous solution and antimicrobial activity of ulvan
      extracted from green seaweed Ulva reticulata.
AB  - The aim of this study is to elucidate the structure and investigate the
      antimicrobial activity of an ulvan obtained by water extraction from green
      seaweed Ulva reticulata collected at Nha Trang sea of Vietnam by using IR, NMR,
      SEC-MALLS and SAXS methods. The ulvan is composed of rhamnose, galactose, xylose,
      manose and glucose (mole ratio Rha: Gal: Xyl: Man: Glu = 1:0.12:0.1:0.06:0.03),
      uronic acid (22.5%) and sulphate groups (17.6%). Chemically structural
      determination showed that the ulvan mainly composed of disaccharide [->4)beta-D
      GlcA(1->4)alpha-L-Rha3S-(1->]. The results from SAXS indicated that ulvan under
      study has a rod-like bulky chain conformation. Ulvan from U. reticulata showed
      high antimicrobial activity, with inhibition zone diameter of 20 mm against
      Enterobacter cloace and 18 mm against Escherichia coli.

PMID- 29199450
TI  - Validity of two POCT glucose measurement devices in hypoglycaemia - how reliable
      is my result?

PMID- 29199451
TI  - The support needs of family caregivers of persons with dementia in India:
      Implications for health services.
AB  - The World Alzheimer's Report estimates that 4.1 million people in India have
      dementia. Caregivers of persons with dementia face physical, psychological,
      social and financial problems related to caring for a person with dementia.
      Literature on the caregiving experience however is highly specific to the
      sociocultural context and cannot be generalized. In low and middle income
      countries much of the caregiving takes place in people's homes and is provided by
      family caregivers. Aim This study aims to explore the needs and challenges of
      family caregivers in Chennai, India. Method Focus group discussions and in-depth
      interviews were conducted using a topic guide. Participants were divided based on
      socio-economic status to ensure homogeneity. An inductive thematic approach was
      used to analyse and code the data. A total of 19 participants took part in the
      study. Results The results capture the experience of caregivers of persons with
      dementia in seeking help and accessing treatment. Priority caregiver needs were
      identified, including the need for sensitised, skilled health workers,
      information on dementia and advanced care needs and cost effective services.
      Conclusion The findings of this study strongly support the need to strengthen
      health systems capacity, make the health care services dementia friendly and cost
      effective. The influence of culture in shaping help seeking was evident in our
      findings. Interventions for caregivers and persons with dementia need to be
      developed and tested so they might be made fit for purpose and scaled up. It will
      be important to identify how these services can be adapted for use in low and
      middle income country resource setting like India.

PMID- 29199452
TI  - Semaphorin-3A and Netrin-1 predict the development of kidney injury in children
      with congenital hydronephrosis.
AB  - Congenital obstructive nephropathy is amongst the main causes of chronic renal
      failure in children. Early diagnosis and initiation of the treatment will delay
      progressive renal tubular atrophy and interstitial fibrosis with the loss of
      nephrons. The aim of this study was to evaluate whether urinary (u) semaphorin-3A
      (SEMA-3A) and Netrin-1 may be potential biomarkers in children with congenital
      hydronephrosis due to ureteropelvic junction obstruction (UPJO). The study
      consisted of 42 children with severe hydronephrosis who needed surgery and two
      control groups (Control One: 42 children with mild, non-obstructive
      hydronephrosis; Control Two: 44 healthy children). All children had normal renal
      function. Urinary semaphorin-3A and Netrin-1 levels were measured in different
      groups using immunoenzymatic ELISA commercial kits. Compared with Control One and
      Control Two groups, the preoperative median uSEMA-3A/creatinine (cr.) and uNetrin
      1/cr. levels increased significantly in the children with severe hydronephrosis
      (p < .01). One month after surgery, uSEMA-3A/cr. and uNetrin-1/cr. levels had
      decreased significantly in the children with severe hydronephrosis (p < .01), but
      were still higher than those in both control groups (p < .05). Receiver operator
      characteristic (ROC) analyses revealed a good diagnostic profile for uSEMA-3A and
      uNetrin-1 in terms of identifying children with a differential renal function of
      <40% [area under the curve (AUC) 0.825 and 0.745, respectively]. Our results
      indicate that increased concentrations of uSEMA-3A and uNetrin-1 are found in
      urine from children with severe hydronephrosis and that their concentrations are
      related to the degree of obstruction.

PMID- 29199453
TI  - Composition of legume soaking water and emulsifying properties in gluten-free
      bread.
AB  - Soaking of legumes results in the loss of macronutrients, micronutrients and
      phytochemicals. Fibre, protein and phytochemicals found in legumes exert
      emulsifying activity that may improve the structure and texture of gluten-free
      bread. The legume soaking water of haricot beans, garbanzo chickpeas, whole green
      lentils, split yellow peas and yellow soybeans were tested in this study for
      functional properties and use as food ingredients. Composition, physicochemical
      properties and effect on the quality of gluten-free bread were determined for
      each legume soaking water. Haricot beans and split yellow peas released the
      highest amount of solids in the legume soaking water: 1.89 and 2.38 g/100 g,
      respectively. Insoluble fibre was the main constituent of haricot beans legume
      soaking water, while water-soluble carbohydrates and protein were the major
      fraction of split yellow peas. High quantities of phenolics (~400 ug/g) and
      saponins (~3 mg/g) were found in the legume soaking water of haricot beans, whole
      green lentils and split yellow peas. High emulsifying activity (46 and 50%) was
      found for the legume soaking water of garbanzo chickpeas and split yellow peas,
      probably due to their protein content and high ratio of water-soluble
      carbohydrates to dry matter. Such activity resulted in softer texture of the
      gluten-free bread. A homogeneous structure of crumb pores was found for split
      yellow peas, opposing that of whole green lentils. A balance between the contents
      of yeast nutrients and antinutrients was the likely basis of the different
      appearances.

PMID- 29199454
TI  - Effects of null mutation of the heat-shock gene htpG on the production of
      virulence factors by Pseudomonas aeruginosa.
AB  - AIM: Pseudomonas aeruginosa is one of the most clinically important opportunistic
      pathogen in humans. The aim of the project was to study effects of HtpG on the
      selected virulence factors responsible for pathogenesis and biofilm formation of
      P. aeruginosa. METHODOLOGY: By characterizing a htpG null mutant of P.
      aeruginosa, we have identified the role of HtpG in the production of selected
      factors. RESULTS: We showed that DeltahtpG mutant affects many physiological
      processes containing: decreased activity of the LasA protease, reduction of
      biofilm formation, decreased motility, and diminished amount of rhamnolipids and
      pyoverdine/pyocyanin. These defects were most evident when the DeltahtpG strain
      was cultured at 42 degrees C. CONCLUSION: Our findings demonstrate the unexplored
      role of HtpG in the pathogenicity of P. aeruginosa, and indicate potential
      targets for antibacterial therapeutics. [Formula: see text].

PMID- 29199455
TI  - Peptide nanomaterials as future antimicrobial technologies.

PMID- 29199456
TI  - Secondary metabolites from the Colletotrichum gloeosporioides A12, an endophytic
      fungus derived from Aquilaria sinensis.
AB  - Two new cyclohexene derivatives colletotricones A and B (1 and 2) and a new
      thiazole derivative colletotricole A (5), along with six known natural
      metabolites were isolated from the extract of Colletotrichum gloeosporioides A12,
      an endophytic fungus derived from Aquilaria sinensis. Among them, the
      colletotricones A and B possess a cyclohexenone skeleton, whereas the
      colletotricole A is a thiazole derivative. Their structures were fully assigned
      with the aid of extensive spectroscopic analysis and data from the literature.
      Moreover, cytotoxic activity in vitro of compounds 1 and 3-9 were evaluated
      against MCF-7, NCI-H460, HepG-2 and SF-268 tumour cell lines. The new compound 1
      exhibited growth inhibitory activity against all the four tumour cell lines with
      IC50 values ranging from 15.7 to 46.8 MUM.

PMID- 29199457
TI  - Urinary tract infections in long-term care facility residents.

PMID- 29199458
TI  - Effect of brief periodic fluoride treatments on the virulence and composition of
      a cariogenic biofilm.
AB  - The present study investigated the effect of periodic 1-min fluoride treatments
      on Streptococcus mutans biofilms and then determined the relationship between
      anti-biofilm activity, treatment frequency, and fluoride concentration using a
      linear-fitting procedure. S. mutans biofilms were periodically treated (1
      min/treatment) with fluoride during biofilm formation and analyzed using
      microbiological methods, confocal microscopy, and real-time PCR. The results
      indicated that reductions in the dry weight and acidogenicity of biofilms due to
      periodic fluoride treatment occurred in a concentration dependent manner. The
      reduction in dry weight without affecting bacterial cell viability was observed
      mainly due to the inhibitory effect of fluoride on gtfB and gtfC gene expression,
      which suppresses EPS production and avoids reduction of the pH below the critical
      point on the tooth surface. This study suggests that brief periodic exposure to
      appropriate fluoride concentrations through mouthwashes and toothpastes may
      affect the virulence and composition of cariogenic biofilms and subsequently
      prevent dental caries.

PMID- 29199459
TI  - Isolation and characterization of mesenchymal stem cells and its antitumor
      application on ovarian cancer cell line.
AB  - The molecular interaction network of Oct-4 (POU5F1) and NANOG connected to
      regulation and growth of mesenchymal stem cells (MSCs) were supplemented with
      information of miRNA to find an important micro-RNAs and supplemented molecular
      interaction network. Following co-culturing of Bone marrow mesenchymal stem cells
      (BMMSCs) with SKOV3 ovarian cancer cell lines and undifferentiated BMMSCs, MTT
      was analyzed for cell cytotoxicity. The analyses of the expression of miRNA were
      performed either after oesteogenesis (hsa-miR-34 and hsa-miR-335) or chondrogenic
      (hsa-miR-145 and hsa-miR-455) differentiation. This molecular interaction network
      was imaged in using software. The results from these findings gave an
      understanding of the main molecular mechanisms regulating MSCs therapeutic
      activity and their undifferentiated state maintenance. We recommend that the
      downregulation of miR-335 is crucial role for tissue homeostasis.

PMID- 29199460
TI  - Isolated massive intraventricular haemorrhage without subarachnoid haemorrhage
      due to rupture of a posterior communicating artery aneurysm.
AB  - The classical presentation of a ruptured intracranial aneurysm is subarachnoid
      haemorrhage (SAH). We present a rare case of a ruptured posterior communicating
      artery (PcomA) aneurysm presented solely with massive intraventricular
      haemorrhage (IVH) in a 53-year-old female. The aneurysm was coiled successfully
      and the outcome of the patient was excellent.

PMID- 29199462
TI  - Role of genetics in peripheral arterial disease outcomes; significance of limb
      salvage quantitative locus-1 genes.
AB  - Peripheral artery disease is a major health care problem with significant
      morbidity and mortality. Humans with peripheral artery disease exhibit two major
      and differential clinical manifestations - intermittent claudication and critical
      limb ischemia. Individuals with intermittent claudication or critical limb
      ischemia have overlapping risk factors and objective measures of blood flow.
      Hence, we hypothesized that variation in genetic make-up may be an important
      determinant in the severity of peripheral artery disease. Previous studies have
      identified polymorphism in genes, contributing to extent of atherosclerosis but
      much less is known about polymorphisms associated with genes that can influence
      peripheral artery disease severity. This review outlines some of the progress
      made up-to-date to unravel the molecular mechanisms underlining differential
      peripheral artery disease severity. By exploring the recovery phenotype of
      different mouse strains following experimental peripheral artery disease, our
      group identified the limb salvage-associated quantitative trait locus 1 on mouse
      chromosome 7 as the first genetic modifier of perfusion recovery and tissue
      necrosis phenotypes. Furthermore, a number of genes within LSq-1, such as ADAM12,
      IL-21Ralpha, and BAG3 were identified as genetic modifiers of peripheral artery
      disease severity that function through preservation of endothelial and skeletal
      muscle cells during ischemia. Taken together, these studies suggest manipulation
      of limb salvage-associated quantitative trait locus 1 genes show great promise as
      therapeutic targets in the management of peripheral artery disease. Impact
      statement Peripheral artery disease (PAD) is a major health care problem with
      significant morbidity and mortality. Individuals with similar atherosclerosis
      burden do display different severity of disease. This review outlines some of the
      progress made up-to-date in unraveling the molecular mechanisms underlining
      differential PAD severity with a focus on the role of the Limb Salvage-associated
      Quantitative trait locus 1 (LSq-1), a key locus in adaptation to ischemia in PAD.

PMID- 29199464
TI  - Sperm RNA elements as markers of health.
AB  - : Idiopathic infertility, an etiology not identified as part of standard clinical
      assessment, represents approximately 20% of all infertility cases. Current male
      infertility diagnosis focuses on the concentration, motility, and morphology of
      spermatozoa. This is of limited value when predicting birth success and of
      limited utility when selecting the optimum treatment. At fertilization,
      spermatozoa provide their genomic contribution, as well as a set of RNAs and
      proteins that have distinct roles in development. The potential of spermatozoal
      RNAs to be used as a prognostic of live birth has been shown [Jodar et al. (2015)
      Science Translational Medicine 7(295):295re6]. This relied on a set of 648 sperm
      RNA elements derived from 285 genes that are perhaps indicative of future health
      status. To address this tenet, the present study correlated the levels of each
      transcript among all samples to assess linkage between transcript absence, birth
      success, and possible disease association. Correlations between transcript levels
      of the 285 genes were analyzed amongst themselves, and within the context of the
      entire transcript population for these samples. The transcripts ACE, GIGYF2, and
      ODF2 had many negative correlations and form the majority of correlations,
      suggesting an important function for these transcripts. Eleven of the 285 queried
      genes had disease-associated variants within a sperm RNA element. Three genes,
      GPX4, NDRG1, and RPS24 had SREs were absent in at least one individual from the
      test cohort. GPX4 and RPS24 are associated with developmental defects and/or
      neonatal lethality. This leaves the intriguing possibility that, while sperm RNAs
      delivered to the oocyte inform the success of live birth, they may also be
      predictors of human health. ABBREVIATIONS: GO: Gene Ontology; ART: assisted
      reproductive technology; IVF: in vitro fertilization; ICSI: intra-cytoplasmic
      sperm injection; RNA-seq: RNA-sequencing; TIC: timed intercourse; IUI:
      intrauterine insemination; SRE: sperm RNA elements; HPA: Human Protein Atlas;
      SMDS: sedaghatian-type spondylometaphyseal dysplasia; DBA: Diamond-Blackfan
      anemia; RPKM: reads per kilobase per million; TPM: transcripts per million; IPA:
      Ingenuity Pathway Analysis; OMIM: Online Mendelian Inheritance in Man.

PMID- 29199461
TI  - Biomarkers: Delivering on the expectation of molecularly driven, quantitative
      health.
AB  - Biomarkers are the pillars of precision medicine and are delivering on
      expectations of molecular, quantitative health. These features have made clinical
      decisions more precise and personalized, but require a high bar for validation.
      Biomarkers have improved health outcomes in a few areas such as cancer,
      pharmacogenetics, and safety. Burgeoning big data research infrastructure, the
      internet of things, and increased patient participation will accelerate discovery
      in the many areas that have not yet realized the full potential of biomarkers for
      precision health. Here we review themes of biomarker discovery, current
      implementations of biomarkers for precision health, and future opportunities and
      challenges for biomarker discovery. Impact statement Precision medicine evolved
      because of the understanding that human disease is molecularly driven and is
      highly variable across patients. This understanding has made biomarkers, a
      diverse class of biological measurements, more relevant for disease diagnosis,
      monitoring, and selection of treatment strategy. Biomarkers' impact on precision
      medicine can be seen in cancer, pharmacogenomics, and safety. The successes in
      these cases suggest many more applications for biomarkers and a greater impact
      for precision medicine across the spectrum of human disease. The authors assess
      the status of biomarker-guided medical practice by analyzing themes for biomarker
      discovery, reviewing the impact of these markers in the clinic, and highlight
      future and ongoing challenges for biomarker discovery. This work is timely and
      relevant, as the molecular, quantitative approach of precision medicine is
      spreading to many disease indications.

PMID- 29199463
TI  - A new C-glycosyl flavone and a new neolignan glycoside from Passiflora edulis
      Sims peel.
AB  - A new C-glycosyl flavone, Chrysin-8-C-(2"-O-beta-6-deoxy-glucopyranosyl)-beta-D
      glucopyranoside (1), a new neolignan glycoside, citrusin G (2), as well as 15
      known compounds (3-17) were isolated from the peel of Passiflora edulis Sims. The
      structure determinations were primarily based on comprehensive spectroscopic
      analyses, and the absolute configuration of 2 were unequivocally determined by
      the CD experiment and chemical transformation. Compound 1 represents the rare
      examples of the flavonoid featuring a deoxy glucose sugar moiety. Compounds 5, 7
      and 9 exhibited moderate inhibitory effects on nitric oxide (NO) production
      stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, with IC50 values of
      34.92, 16.12 and 26.67 MUM, respectively.

PMID- 29199465
TI  - 12 Years delayed postoperative spinal recurrence of craniopharyngioma. Case
      report and literature review.
AB  - A case of delayed spinal adamantinomatous craniopharyngioma recurrence is
      presented. A 54-year-old male patient was admitted in our Emergency Department
      complaining of urinary disorders and leg pains. He underwent surgical removal of
      intraventricular craniopharyngioma 12 years previously. On MR imaging a well
      circumscribed intradural cistyc mass at the T12 level was reavealed. A T11 and
      T12 laminotomy was performed and total removal of the tumour was achieved.
      Histology examination showed adamantinous craniopharyngioma. The authors believe
      that this represents the third case described of spinal craniofaryngioma
      recurrence and the first involving the dorsal spine.

PMID- 29199466
TI  - Toxicological evaluation in silico and in vivo of secondary metabolites of
      Cissampelos sympodialis in Mus musculus mice following inhalation.
AB  - The ethanolic extract of the leaves of Cissampelos sympodialis showed great
      pharmacological potential, with inflammatory and immunomodulatory activities,
      however, it showed some toxicological effects. Therefore, this study aims to
      verify the toxicological potential of alkaloids of the genus Cissampelos through
      in silico methodologies, to develop a method in LC-MS/MS verifying the presence
      of alkaloids in the infusion and to evaluate the toxicity of the infusion of the
      leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed
      that alkaloid 93 presented high toxicological potential along with the products
      of its metabolism. LC-MS/MS results showed that the infusion of the leaves of
      this plant contained the alkaloids warifteine and methylwarifteine. Finally, the
      in vivo toxicological analysis of the C. sympodialis infusion showed results,
      both in biochemistry, organ weights and histological analysis, that the infusion
      of C. sympodialis leaves presents a low toxicity.

PMID- 29199467
TI  - Primary Calvarial Tuberculosis: a report of three cases.
AB  - Calvarial tuberculosis is rare presentation and has been reported in only about
      0.01% of all patients with mycobacterial infections. Though rare, the incidence
      of Calvarial tuberculosis seems to be on the rise, especially in developing
      countries. We present three cases of Calvarial tuberculosis which were
      successfully managed at our Centre. All the cases occurred de novo in young,
      otherwise healthy individuals, hailing from good socio-economic backgrounds and
      without any past history or contact history with tuberculosis patients. We
      highlight the importance of keeping this diagnosis in mind in appropriate
      clinical situations as well as recommend the early commencement of optimal
      management to prevent serious neurologic complications & sequelae.

PMID- 29199468
TI  - Chemical composition of Helietta parvifolia and its in vitro anticholinesterase
      activity.
AB  - The chemical composition of the essential oil and the n-hexane (Hex), Ethyl
      Acetate (EtOAc) and butanol (BuOH) extracts from the leaves of Helietta
      parvifolia were determined by detailed GC-MS analysis, spectroscopic and
      spectrometric data. Eighty-four compounds were identified, revealing a
      furoquinoline alkaloid-rich composition. The phytochemical analysis of the
      extracts allowed the isolation of eigth furoquinoline alkaloids. Retention
      indices in GC-MS for six of this alkaloids are reported for the first time.
      Furoquinoline alkaloids are acethylcholinesterase inhibitors. Thus, the essential
      oil and extracts were submitted to this in vitro assay. The EtOAc and BuOH
      extracts showed potent activity, with IC50 of 9.7 and 12.9 MUg mL-1,
      respectively. Additionaly, a correlation of their chemical constituents,
      established by principal component analysis (PCA) demostrated a similar profile
      and a high content of alkaloids. It is for these reasons that we can assume that
      the alkaloid content in these extracts could be responsible for their
      anticholinesterase activity.

PMID- 29199469
TI  - An exploratory study of the long-term impact of difficulty kneeling after total
      knee replacement.
AB  - PURPOSE: To explore the long-term impact of difficulty with kneeling and how
      healthcare services could be improved to help patients kneel after total knee
      replacement. PATIENTS AND METHODS: Telephone interviews were conducted with 56
      patients who had extreme difficulty kneeling at 7-10 years after knee
      replacement. Patients were asked about reasons for difficulty kneeling, how it
      impacted upon their lives, and experiences of healthcare services. Responses were
      recorded on a standardized proforma and a descriptive content analysis performed.
      RESULTS: Most people had difficulty kneeling because of pain or discomfort in the
      replaced knee. Many patients described how this limitation affected their daily
      lives, including housework, gardening, religious practices, leisure activities
      and getting up after a fall. Patients often adapted to these limitations by
      finding alternatives to kneeling, assistance from others or home adaptations.
      Many patients had accepted that they could not kneel, however some still
      expressed frustrated. Few patients had consulted with healthcare professionals
      about kneeling difficulties, and unmet needs included the provision of
      information about kneeling and post-operative physiotherapy. INTERPRETATION: This
      study provides an initial insight into how difficulty kneeling after knee
      replacement impacts upon patientsand the need for better healthcare provision.
      Implications for rehabilitation Rehabilitation professionals should be aware that
      many patients experience difficulty with kneeling after total knee replacement
      and that this has a long-term impact upon patients. There is a need for
      rehabilitation after knee replacement to address kneeling difficulties. It is
      suggested that this rehabilitation should be delivered early in the postoperative
      recovery phase and designed to address the multifactorial reasons that patients
      find kneeling problematic.

PMID- 29199470
TI  - Risk Factors for 30-Day Complications After Thumb CMC Joint Arthroplasty: An
      American College of Surgeons National Surgery Quality Improvement Program Study.
AB  - BACKGROUND: The first carpometacarpal (CMC) joint is a common site of
      osteoarthritis, with arthroplasty being a common procedure to provide pain relief
      and improve function with low complications. However, little is known about risk
      factors that may predispose a patient for postoperative complications. METHODS:
      All CMC joint arthroplasty from 2005 to 2015 in the prospectively collected
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) database were identified. Bivariate testing and multiple logistic
      regressions were performed to determine which patient demographics, surgical
      variables and medical comorbidities were significant predictors for
      complications. These included wound related, cardiopulmonary, neurological and
      renal complications, return to the operating room (OR) and readmission. RESULTS:
      A total of 3344 patients were identified from the database. Of those, 45 patients
      (1.3%) experienced a complication including wound issues (0.66%), return to the
      OR (0.15%) and readmission (0.27%) amongst others. When performing bivariate
      analysis, age over 65, American Society of Anesthesiologists (ASA) Class,
      diabetes and renal dialysis were significant risk factors. Multiple logistic
      regression after adjusting for confounding factors demonstrated that insulin
      dependent diabetes and ASA Class 4 had a strong trend while renal dialysis was a
      significant risk factor. CONCLUSIONS: CMC arthroplasty has a very low overall
      complication rate of 1.3% and wound complication rate of 0.66%. Diabetes
      requiring insulin and ASA Class 4 trended towards significance while renal
      dialysis was found to be a significant risk factors in logistic regression. This
      information may be useful for preoperative counseling and discussion with
      patients who have these risk factors.

PMID- 29199471
TI  - Outcomes of Triceps Rupture in the US Military: Minimum 2-Year Follow-up.
AB  - BACKGROUND: The objective of this study was to examine the subjective and
      objective midterm functional clinical outcomes of surgically repaired triceps
      injuries in a moderate- to high-demand population. METHODS: The US Military
      Health System was queried to identify all surgically treated triceps tendon
      ruptures between 2008 and 2013. Primary endpoints included rates of rerupture,
      perioperative complications, or significant persistent elbow dysfunction;
      Disability of the Arm, Shoulder and Hand (DASH) score, Mayo Elbow score, and
      ability to do push-ups were also extracted. RESULTS: Thirty-seven patients
      underwent triceps tendon repair with a mean follow-up of 49.8 +/- 17.3 months
      (range: 26.8-80.2). The most common mechanisms of injury were military duties
      (27%), sporting activity (24%), or fall-related (21.6%), with most injuries
      occurring during an eccentric movement (54%). While 45% experienced occasional
      elbow pain postoperatively, only 1 patient (2.7%) had a rerupture. Despite this,
      at 2 years, 31 patients (84%) were able to return to full military duty. While 6
      patients were discharged from military service, only 1 underwent medical
      separation while 5 retired for reasons unrelated to their triceps tendon rupture.
      Patient-reported outcomes were available for 14 patients at final follow-up. The
      average DASH and Mayo Elbow scores were 4.7 (SD +/- 4.7, range: 0-15.9) and 85.4
      (SD +/- 11.7, range: 60-100), respectively. The cohort could perform mean 54.2
      (range: 9-90) push-ups. In additional, 12 of 14 (85.7%) were satisfied with their
      elbow function. CONCLUSIONS: The active duty cohort experienced excellent
      postoperative results with a high rate of return to military duty, despite nearly
      half of the patients recognizing some degree of activity-related, elbow pain.

PMID- 29199472
TI  - Behavior of Caenorhabditis elegans in a nicotine gradient modulated by food.
AB  - Nicotine decreases food intake, and smokers often report that they smoke to
      control their weight. To see whether similar phenomena could be observed in the
      model organism Caenorhabditis elegans, we challenged drug-naive nematodes with a
      chronic low (0.01 mM) and high (1 mM) nicotine concentration for 55 h (from
      hatching to adulthood). After that, we recorded changes in their behavior in a
      nicotine gradient, where they could choose a desired nicotine concentration. By
      using a combination of behavioral and morphometric methods, we found that both
      nicotine and food modulate worm behavior. In the presence of food (E. coli OP50)
      the nematodes adapted to the low nicotine concentration, when placed in the
      gradient, chose a similar nicotine concentration like C. elegans adapted to the
      high nicotine concentration. However, in the absence of food, the nematodes
      adapted to the low nicotine concentration, when placed in the gradient of this
      alkaloid, chose a similar nicotine concentration like naive worms. The nematodes
      growing up in the presence of high concentrations of nicotine had a statistically
      smaller body size, compared to the control condition, and the presence of food
      did not cause any enhanced slowing movement. These results provide a platform for
      more detailed molecular and cellular studies of nicotine addiction and food
      intake in this model organism.

PMID- 29199473
TI  - Sun Protection Among New Zealand Primary School Children.
AB  - Schools are an important setting for raising skin cancer prevention awareness and
      encouraging sun protection. We assessed the clothes worn and shade used by 1,278
      children in eight schools in the Wellington region of New Zealand. These children
      were photographed for the Kids'Cam project between September 2014 and March 2015
      during school lunch breaks. Children's mean clothing coverage (expressed as a
      percentage of body area covered) was calculated. Data on school sun-safety
      policies were obtained via telephone. Mean total body clothing coverage was 70.3%
      (95% confidence interval = 66.3%, 73.8%). Body regions with the lowest mean
      coverage were the head (15.4% coverage), neck (36.1% coverage), lower arms (46.1%
      coverage), hands (5.3% coverage), and calves (30.1% coverage). Children from
      schools with hats as part of the school uniform were significantly more likely to
      wear a hat (52.2%) than children from schools without a school hat (2.7%). Most
      children (78.4%) were not under the cover of shade. Our findings suggest that New
      Zealand children are not sufficiently protected from the sun at school. Schools
      should consider comprehensive approaches to improve sun protection, such as the
      provision of school hats, sun-protective uniforms, and the construction of
      effective shade.

PMID- 29199474
TI  - Effects of maternal exposure to extract of Trichilia catigua on antibody
      production in the offspring of Wistar rats.
AB  - It was evaluated the effects of maternal treatment with the Trichilia catigua
      (ExTc) crude extract on the antibodies' production by their offspring. Female
      rats received ExTc or saline from the first day of pregnancy until the twenty
      first day after the birth of the pups, when the pups were weaned. All pups were
      inoculated with two doses of 50 MUg of IgY diluted in aluminium hydroxide/PBS on
      days 26 and 40 of life. Antibody levels were analysed by ELISA. Our results show
      an increase in levels of IgG1 and IgG2a anti-IgY in female offspring of mothers
      treated with ExTc compared to female offspring of untreated mothers. Furthermore,
      ExTc treatment suppressed the production of IgG2a anti-IgY antibodies in males.
      The data show that maternal exposure to ExTc can modulate the production of
      antibodies in the offspring.

PMID- 29199475
TI  - Chromosomal instability and cytotoxicity induced by ribavirin: comparative
      analysis in cell lines with different drug-metabolizing profiles.
AB  - Ribavirin is an important component of the treatment for hepatitis C virus (HCV)
      infection and, in combination with the new direct-acting antiviral (DAA) agents,
      comprises the major current therapeutic regimens. This study evaluated the
      cytotoxicity and chromosomal instability induced by ribavirin using the in vitro
      cytokinesis-block micronucleus cytome (CBMN-Cyt) assay in two cell lines with
      different expression levels of drug-metabolizing enzymes: human hepatocellular
      carcinoma cells (HepG2) and Chinese hamster ovary (CHO-K1) cells. HepG2 cells
      were treated with nine concentrations (from 15.3 MUg/ml to 3.9 mg/ml) and CHO-K1
      cells were exposed to eight concentrations (from 15.3 MUg/ml to 1.9 mg/ml) of
      ribavirin for 24 h. Ribavirin inhibited cell proliferation in both cell lines,
      but at different concentrations: 3.9 mg/ml in HepG2 and 244.2 MUg/ml in CHO-K1
      cells. No significant differences were observed regarding aspects of cell death
      in HepG2 and CHO-K1 cells, reflecting the absence of cytotoxic effects associated
      to ribavirin. Ribavirin did not increase the frequency of nucleoplasmic bridges
      (NPBs) and nuclear bud (NBUD). However, when compared to the negative control, a
      significant increase in micronuclei (MNi) frequency was observed in both cell
      lines. However, chromosomal instability was induced by higher concentrations of
      ribavirin in HepG2 cells (from 61.1 to 976.8 MUg/ml), compared with CHO-K1 cells
      (15.3 and 30.5 MUg/ml). These results demonstrate the potential of ribavirin to
      promote chromosomal instability, and suggest that cells with different
      expressions of drug-metabolizing enzymes show different susceptibility to
      ribavirin effects.

PMID- 29199476
TI  - Sexual Violence Victimization Among Youth Presenting to an Urban Emergency
      Department: The Role of Violence Exposure in Predicting Risk.
AB  - Sexual violence (SV) is a widespread public health problem among adolescents and
      emerging adults with significant short- and long-term consequences. Young people
      living in urban, disadvantaged communities with high rates of violence may be
      especially at risk for SV victimization. Understanding interconnections between
      different forms of violence is critical to reducing SV risk among youth.
      Participants were youth ( N = 599) ages 14 to 24 years ( M = 20.05, SD = 2.42)
      presenting to an urban emergency department with a Level 1 trauma designation as
      part of a prospective cohort study and followed-up for 24 months. We used
      logistic regression to examine the probability of reporting SV during the 24
      month follow-up based on baseline reports of community and peer violence
      exposure, accounting for previous SV victimization, substance use, and
      sociodemographic characteristics. Among youth presenting to an urban emergency
      department, 22% of youth not seeking care for a sexual assault reported any
      lifetime SV (forced and/or substance-induced sexual intercourse) at baseline.
      During the 24-month follow-up, 12% reported SV victimization. We found high
      community violence exposure (odds ratio [OR] = 2.96, 95% confidence interval [CI]
      [1.01, 8.68]) and peer violence exposure (OR = 1.58, 95% CI [1.19, 2.08]) were
      associated with increased odds of reporting SV during follow-up in addition to
      previous SV victimization (OR = 2.71, 95% CI [1.45, 5.09]). Sex, age, parent
      education, and alcohol or other drug use at baseline were not associated with
      odds of SV during follow-up. Investigating interconnections between SV
      victimization and other forms of violence across socioecological levels provides
      an opportunity to advance SV research and identify promising avenues for
      prevention based on other violence prevention research. Future strategies for SV
      prevention that incorporate community and peer components as well as SV-specific
      content may help reduce SV victimization among youth living in urban,
      disadvantaged communities.

PMID- 29199477
TI  - Phenylpropanoid glucosides from Tadehagi triquetrum inhibit oxLDL-evoked foam
      cell formation through modulating cholesterol homeostasis in RAW264.7
      macrophages.
AB  - The phenylpropanoid glucosides from Tadehagi triquetrum were found to be
      beneficial to glucose and lipid metabolism in vitro. Herein, we investigated the
      effects of these compounds on oxidised low-density lipoprotein (oxLDL)-induced
      foam cell formation in RAW264.7 macrophages, aiming to evaluate their potential
      utility in prevention of atherosclerosis. Our results showed that three out of
      seven phenylpropanoid glucosides significantly inhibited oxLDL-evoked foam cell
      formation. These three compounds remarkably inhibited cholesterol influx and
      enhanced cholesterol efflux. Treatment with compounds 3, 4 and 7 significantly
      down-regulated the expression of scavenge receptors 1 (SR-1) and cluster of
      differentiation 36 (CD36) and increased the expression ATP-binding cassette
      transporters A1 and G1 (ABCA1 and ABCG1). Analyses of structure-activity
      relationships revealed that cinnamyl group was the most pivotal group for their
      activities. This work provided phenomenon that these phenylpropanoid glucosides
      are effective regulator of cholesterol influx/efflux and may be useful in leading
      for development of anti-atherosclerotic agents.

PMID- 29199478
TI  - Effect of certain non-steroidal anti-inflammatory drugs on the paraoxonase 2
      (PON2) in human monocytic cell line U937.
AB  - The paraoxonase gene family in humans consists of three members as PON1, PON2 and
      PON3. PON2 can be expressed in several tissues; however, it is not released from
      the cells in those tissues. PON2 is also expressed in macrophages. Firstly, the
      commonly used NSAIDs diclofenac sodium and tenoxicam were applied on U937 cell
      line, the in vitro human monocyte cell line. Than PON2 specific Lactonase
      activity and paraoxonase family specific arylesterase were determined. Use of
      Diclofenac sodium in 0.845 mM dose during 6-12 h of incubation and Tenoxicam in
      0.74 mM dose during 6 h of incubation resulted in a significant decline in the
      lactonase activity. Diclofenac sodium didn't make any change in the arylesterase
      activity. On the other hand, tenoxicam decreased arylesterase activity during the
      use of 12 h, in 0.74 mM and 1.48 mM dose.

PMID- 29199479
TI  - A Statistical Study of Metatarsal Anatomy: Toward the Design of Wide-Range
      Prosthetic Solutions.
AB  - : The aim of the study is to provide some characteristic parameters of the
      anatomy of metatarsals from computed tomography (CT) scans. These data are
      important for more anatomical metatarsal head resurfacing prosthesis conception.
      Measures were performed on 20 CT scans from 17 patients with a mean age of 44.35
      +/- 15.75 years old. The panel was composed of 40% male and 50% left feet.
      Measurements were divided in 2 distinct categories: linear measurements with
      length of metatarsal, head radius and head, and diaphysis and base thicknesses,
      and cross-sectional area measurements, including cortical and cancellous bone
      area at 10%, 25%, 50%, 60%, 75%, and 90% of the metatarsal's length. The results
      included the mean and SD found for each measured value. This study is the first
      step toward a better understanding of the metatarsal's anatomy, so as to design a
      more anatomical range of metatarsal head resurfacing implants. LEVELS OF
      EVIDENCE: Level IV.

PMID- 29199480
TI  - Citizens' understanding of welfare of animals on the farm: An empirical study.
AB  - Many people believe that welfare standards for nonhuman animals on farms need to
      be improved. However, the definition of farm animal welfare (FAW) remains
      unclear, as different disciplines have developed competing understandings of FAW.
      Some studies have investigated citizens' understanding of FAW through
      quantitative surveys. This study combined both closed-ended and open-ended
      questions and compared the findings from the different types of questions. For
      the open-ended question, respondents mostly named criteria in the categories of
      "housing system" and "management practice"; however, for the closed-ended
      question, the category "animal health" was most important. These findings suggest
      that not only whom you ask determines what comprises animal welfare, but how you
      ask. These findings should be considered when developing new animal welfare
      programs to increase the likelihood that the new programs will be accepted by the
      broader public and meet its expectations. In particular, improvements concerning
      animal health need to be publicized and clearly communicated to citizens, as
      health-related aspects are important to many people even though those aspects may
      not be the first thing they mentioned when asked.

PMID- 29199481
TI  - The conversational position in endoscopic pituitary surgery.
AB  - We describe a novel patient position for endoscopic transphenoidal surgery - the
      'conversational position'. This position is a safe and effective alternative to
      the standard supine position, incorporating a semi-sitting position with the
      additional innovation of achieving a 'conversational position' by flexing the
      neck and turning the patient's head turned to face the surgeon. The
      'conversational' position offers improvements in the surgical approach to sellar
      region, addressing specific intraoperative challenges such as maintaining a
      bloodless operative field, and enabling more intuitive and ergonomic surgical
      workflow.

PMID- 29199482
TI  - Low dose anti-thymocyte globulin reduces chronic graft-versus-host disease
      incidence rates after matched unrelated donor transplantation.
AB  - Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell
      transplant conditioning regimens to prevent graft rejection and reduce graft
      versus-host disease (GVHD). Doses used in retrospective and prospective clinical
      trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and
      chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes
      in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG
      IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n =
      48) without ATG. One year cumulative incidence of chronic GVHD was 25.2% in the
      MUD group versus 33.3% in the MRD group (p = .5). One-year cumulative incidence
      of extensive chronic GVHD was 9.6% in the MUD group versus 26.6% in the MRD group
      (p = .042). Our analysis supports the use of low dose ATG in MUD transplantation
      as an effective therapy to prevent chronic GVHD.

PMID- 29199483
TI  - Anthropometric and metabolic improvements in human type 2 diabetes after
      introduction of an Okinawan-based Nordic diet are not associated with changes in
      microbial diversity or SCFA concentrations.
AB  - The Okinawan-based Nordic (O-BN) diet improves anthropometry and metabolism in
      type 2 diabetes mellitus (T2DM) patients. The aim of this study was to study
      mechanisms behind improvements by examining Enterobacteriaceae abundance,
      microbial diversity, and concentrations of short-chain fatty acids (SCFAs). A
      secondary aim was exploring if metformin treatment affects microbiota or SCFAs.
      Thirty T2DM patients received the O-BN diet for 12 weeks. Faecal and blood
      samples were collected at baseline, 12 and 28 weeks. Although patients
      experienced weight loss and improved metabolic parameters, there were no
      significant changes in Enterobacteriaceae abundance or microbial diversity.
      Patients on metformin displayed higher Enterobacteriaceae abundance throughout
      the study (p = .008, p = .038, and p = .001, respectively). Isovaleric acid was
      decreased after 12 weeks (p = .018). Butyric acid was decreased at follow-up (p =
      .007). Improved anthropometry and metabolism in T2DM after introduction of the O
      BN diet is not associated with changes in Enterobacteriaceae abundance, microbial
      diversity or SCFA concentrations.

PMID- 29199484
TI  - Symmetric molecules with 1,4-triazole moieties as potent inhibitors of tumour
      associated lactate dehydrogenase-A.
AB  - A series of symmetric molecules incorporating aryl or pyridyl moieties as central
      core and 1,4-substituted triazoles as a side bridge was synthesised. The new
      compounds were investigated as lactate dehydro-genase (LDH, EC 1.1.1.27)
      inhibitors. The cancer associated LDHA isoform was inhibited with IC50 = 117-174
      uM. Seven compounds exhibited better LDHA inhibition (IC50 117-136 uM) compared
      to known LDH inhibitor - galloflavin (IC50 157 uM).

PMID- 29199485
TI  - A safety evaluation of raltegravir for the treatment of HIV.
AB  - INTRODUCTION: Raltegravir (RAL) was the first commercialized agent from a new
      drug class with an innovative target, the integrase. Since its introduction in
      clinical practice RAL has become widely used for the treatment of HIV-1 infected
      patients. A decade after its approval, this article reviews key evidence from RAL
      with a special interest on safety outcomes. Areas covered: Pharmacologic, safety
      and efficacy data of RAL from clinical trials and post-commercialization
      published reports are hereby summarized after a literature review including
      PubMed search, relating proceedings and abstracts from relevant international HIV
      conferences, assessment reports from European and United States regulatory
      agencies and treatment guidelines (World Health Organization, United States
      Department of Health and Human Services and European AIDS Clinical Society), up
      to October 2017. Most frequent search terms were 'raltegravir', 'safety',
      'adverse events', 'efficacy' and 'integrase-inhibitors'. Expert opinion: Despite
      the arrival of new integrase strand transfer inhibitors (INSTIs) with advantages
      in terms of dosing convenience (elvitegravir, ELV) and higher genetic barrier
      (dolutegravir, DTG), RAL has stood the test of time and its overall favourable
      safety profile, without significant appearance of unexpected adverse events,
      vouch for its relevance in the antiretroviral armamentarium.

PMID- 29199486
TI  - Series: Practical guidance to qualitative research. Part 3: Sampling, data
      collection and analysis.
AB  - In the course of our supervisory work over the years, we have noticed that
      qualitative research tends to evoke a lot of questions and worries, so-called
      frequently asked questions (FAQs). This series of four articles intends to
      provide novice researchers with practical guidance for conducting high-quality
      qualitative research in primary care. By 'novice' we mean Master's students and
      junior researchers, as well as experienced quantitative researchers who are
      engaging in qualitative research for the first time. This series addresses their
      questions and provides researchers, readers, reviewers and editors with
      references to criteria and tools for judging the quality of qualitative research
      papers. The second article focused on context, research questions and designs,
      and referred to publications for further reading. This third article addresses
      FAQs about sampling, data collection and analysis. The data collection plan needs
      to be broadly defined and open at first, and become flexible during data
      collection. Sampling strategies should be chosen in such a way that they yield
      rich information and are consistent with the methodological approach used. Data
      saturation determines sample size and will be different for each study. The most
      commonly used data collection methods are participant observation, face-to-face
      in-depth interviews and focus group discussions. Analyses in ethnographic,
      phenomenological, grounded theory, and content analysis studies yield different
      narrative findings: a detailed description of a culture, the essence of the lived
      experience, a theory, and a descriptive summary, respectively. The fourth and
      final article will focus on trustworthiness and publishing qualitative research.

PMID- 29199487
TI  - 2',4-Dihydroxy-3',4',6'-trimethoxychalcone from Chromolaena odorata possesses
      anti-inflammatory effects via inhibition of NF-kappaB and p38 MAPK in
      lipopolysaccharide-activated RAW 264.7 macrophages.
AB  - CONTEXT: Immune dysregulation has been implicated in the pathogenesis of many
      diseases. Macrophages play a crucial role contributing to the onset, progression,
      and resolution of inflammation. Macrophage inflammatory mediators are of
      considerable interest as potential targets to treat inflammatory diseases.
      OBJECTIVE: The present study was conducted to elucidate the anti-inflammatory
      mechanism of 2',4-dihydroxy-3',4',6'-trimethoxychalcone (1), the major chalcone
      isolated from Chromolaena odorata (L.) R.M.King & H.Rob, against
      lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. MATERIALS
      AND METHODS: Cell viability, nitric oxide (NO), and proinflammatory cytokines of
      LPS-activated RAW 264.7 cells were measured by MTT, Griess, and ELISA assays,
      respectively. Cell lysates were subjected to Western blotting for investigation
      of protein expression. RESULTS AND DISCUSSION: Treatment with the major chalcone
      1 significantly attenuated the production of NO and proinflammatory cytokines,
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in a dose
      dependent manner. The chalcone suppressed nuclear factor-kappaB (NF-kappaB)
      stimulation by preventing activation of inhibitor kappaB kinase (IKK) alpha/beta,
      degradation of inhibitor kappaB (IkappaB) alpha, and translocation of p65 NF
      kappaB into the nucleus. Additionally, the chalcone markedly repressed the
      phosphorylation of p38 mitogen-activated protein kinase (MAPK), but no further
      inhibition was detected for c-Jun N-terminal activated kinases or extracellular
      regulated kinases. Thus, suppression of NF-kappaB and p38 MAPK activation may be
      the core mechanism underlying the anti-inflammatory activity of 2',4-dihydroxy
      3',4',6'-trimethoxychalcone (1). CONCLUSION: These findings provide evidence that
      2',4-dihydroxy-3',4',6'-trimethoxychalcone (1) possesses anti-inflammatory
      activity via targeting proinflammatory macrophages. This anti-inflammatory
      chalcone is a promising compound for reducing inflammation.

PMID- 29199488
TI  - Which dietary patterns are more likely to be associated with aspects of eco
      sustainable food behaviours in Italy?
AB  - Sustainable food consumption (SFC) policies need further investigation into
      eating habits to improve interventions to encourage shifting to new consumption
      patterns respectful of human rights, environment and health. Reversing the usual
      approach focussed on sustainable consumer, the present study investigates how
      different eating patterns relate to eco-sustainable food. A cluster analysis was
      carried out on consumption frequencies of food groups recorded in an Italian
      national survey on 3004 respondents, providing four eating habit segments,
      further investigated as for sustainable food attitude and behaviour. Openness to
      eco-sustainable food is found mostly in the more balanced diet segment,
      accounting for about one third of the adult Italian population. Inaccessibility,
      non-affordability, unhealthy diet and a lack of information still negatively
      condition eating habits to the detriment of more sustainable consumption. These
      findings could support SFC stakeholders in targeting policies and strategies
      based on diversified approaches to enhance awareness of SFC issues.

PMID- 29199489
TI  - Crystal structure of the human carbonic anhydrase II adduct with 1-(4
      sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane
      impermeant, isoform selective inhibitor.
AB  - Pyridinium containing sulfonamides have been largely investigated as carbonic
      anhydrase inhibitors (CAIs), showing interesting selectivity features.
      Nevertheless, only few structural studies are so far available on adducts that
      these compounds form with diverse CA isoforms. In this paper, we report the
      structural characterization of the adduct that a triphenylpyridinium derivative
      forms with hCA II, showing that the substitution of the pyridinium ring plays a
      key role in determining the conformation of the inhibitor in the active site and
      consequently the binding affinity to the enzyme. These findings open new
      perspectives on the basic structural requirements for designing sulfonamide CAIs
      with a selective inhibition profile.

PMID- 29199490
TI  - The role of electroencephalogram in neonatal seizure detection.
AB  - INTRODUCTION: The role of EEG in neonatal seizure detection is well-established,
      being the multichannel video-EEG the gold standard. However, in the clinical
      practice often amplitude integrated EEG (aEEG) is used, in order to overcome the
      difficulties related to EEG use. Areas covered: An overview regarding neonatal
      seizures, current tools used to detect these (multichannel EEG versus aEEG) with
      respective strenghts and limitations, and some tools that can implement the use
      of multichannel EEG in the NICU. Expert commentary: Multichannel video-EEG is
      still a gold standard for seizure detection. Indeed, this tool allows to avoid
      both underestimation of neonatal seizure incidence and overtreatment with
      anticonvulsant drugs. Furthermore, it has to be acknowledged that multichannel
      video-EEG monitoring is not limited to the only seizure detection, providing also
      the information needed for a more accurate assessment of the background activity
      and some specific waves/pattern and features indicative of the brain development.

PMID- 29199492
TI  - Development of B-cell prolymphocytic leukemia in a patient with splenic diffuse
      red pulp small B-cell lymphoma.

PMID- 29199491
TI  - New pentadienone oxime ester derivatives: synthesis and anti-inflammatory
      activity.
AB  - To develop novel anti-inflammatory agents, a series of new pentadienone oxime
      ester compounds were designed and synthesized. The structures were determined by
      IR, 1H NMR, 13 C NMR, and HRMS. All compounds have been screened for their anti
      inflammatory activity by evaluating their inhibition against LPS-induced nitric
      oxide (NO) release in RAW 264.7 cell. Among them, compound 5j was found to be one
      of the most potent compounds in inhibiting NO and IL-6 (IC50 values were 6.66 uM
      and 5.07 uM, respectively). Preliminary mechanism studies show that title
      compound 5j could significantly suppress expressions of nitric oxide synthase,
      COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein
      kinases/NF-kappaB signalling pathway. These data support further studies to
      assess rational design of more efficient pentadienone oxime ester derivatives
      with anti-inflammatory activity in the future.

PMID- 29199493
TI  - Antenatal vaccination to decrease pertussis in infants: safety, effectiveness,
      timing, and implementation.
AB  - Pertussis remains a serious global health issue in infants aged less than 6
      months. Neonates and young infants have the highest risk of developing pertussis
      as they are too young to be vaccinated and thus are more likely to develop more
      severe pertussis-related complications, including death. Protecting this
      vulnerable age population from pertussis is considered a main priority in many
      national health programs. Two vaccine strategies exist to protect infants from
      pertussis: "cocooning" and maternal vaccination during pregnancy. The latter is
      the more recent and preferred strategy, which protects newborns by passive
      transplacental transfer of pertussis antibodies. We review the reported evidence
      on the safety, effectiveness, timing and implementation of this antenatal
      immunization strategy.

PMID- 29199494
TI  - Putting Out Fires: Understanding the Developmental Nature and Roles of Inmate
      Gangs in the Philippine Overcrowded Jails.
AB  - Utilizing intensive interview data from inmates in one of the most overcrowded
      and underresourced jails in Metro Manila, Philippines, this article explores the
      origins and roles of inmate pangkats (a derivative of gangs) in jail management.
      Responding to institutional deficiencies, such as police misconduct and court
      case delays, and structural shortages, such as lack of space, operational
      resources, and personnel, this article investigates how the pangkats supplement
      jail management and help keep the jail operations afloat. Specifically, this
      article documents how the pangkats put out fires: their intricate roles in
      mitigating pains of imprisonment, conflict mediation, order maintenance, and
      instilling discipline among their members. This article also details the
      emergence of a give-and-take relationship that develops between and among the
      pangkats and jail officials that are reflective of the Philippine sociocultural
      realities. Implications to theory on prison community and policy on gang
      management in a developing country context are discussed.

PMID- 29199495
TI  - Food perception at lunchtime does not depend on the nutritional and perceived
      characteristics of breakfast.
AB  - Breakfast consumption can entail nutritional advantages positively affecting food
      choices. This study investigated the effect of minor changes in breakfast
      composition on the perceived attributes of foods, both at breakfast and at
      lunchtime. Four breakfasts were defined considering nutritional and perceptual
      factors. Three breakfasts varied just for a single cereal-based chocolate
      containing food item, while a control breakfast mimicked fasting conditions.
      Breakfast perception was assessed before and after consumption. Subjects rated
      breakfast energy content on the basis of single items, while judged breakfast
      healthiness as a whole, suggesting that the combination of different ingredients
      can modify the perceived health value of foods. Additionally, 4 h after
      breakfast, a perceptual evaluation of lunch-related food images was performed,
      without differences among breakfasts. This study extends current knowledge on the
      relationship between subjective perceptual attributes and objective energy value
      and food composition, as well as on breakfast impact on food perception at
      lunchtime.

PMID- 29199497
TI  - Erratum.

PMID- 29199496
TI  - Recent trends on the role of epigenomics, metabolomics and noncoding RNAs in
      rationalizing mood stabilizing treatment.
AB  - Mood stabilizers are the cornerstone in treatment of mood disorders, but their
      use is characterized by high interindividual variability. This feature has
      stimulated intensive research to identify predictive biomarkers of response and
      disentangle the molecular bases of their clinical efficacy. Nevertheless,
      findings from studies conducted so far have only explained a small proportion of
      the observed variability, suggesting that factors other than DNA variants could
      be involved. A growing body of research has been focusing on the role of
      epigenetics and metabolomics in response to mood stabilizers, especially lithium
      salts. Studies from these approaches have provided new insights into the
      molecular networks and processes involved in the mechanism of action of mood
      stabilizers, promoting a systems-level multiomics synergy. In this article, we
      reviewed the literature investigating the involvement of epigenetic mechanisms,
      noncoding RNAs and metabolomic modifications in bipolar disorder and the
      mechanism of action and clinical efficacy of mood stabilizers.

PMID- 29199498
TI  - GPGPU-based explicit finite element computations for applications in
      biomechanics: the performance of material models, element technologies, and
      hardware generations.
AB  - Finite element (FE) simulations are increasingly valuable in assessing and
      improving the performance of biomedical devices and procedures. Due to high
      computational demands such simulations may become difficult or even infeasible,
      especially when considering nearly incompressible and anisotropic material models
      prevalent in analyses of soft tissues. Implementations of GPGPU-based explicit
      FEs predominantly cover isotropic materials, e.g. the neo-Hookean model. To
      elucidate the computational expense of anisotropic materials, we implement the
      Gasser-Ogden-Holzapfel dispersed, fiber-reinforced model and compare solution
      times against the neo-Hookean model. Implementations of GPGPU-based explicit FEs
      conventionally rely on single-point (under) integration. To elucidate the expense
      of full and selective-reduced integration (more reliable) we implement both and
      compare corresponding solution times against those generated using
      underintegration. To better understand the advancement of hardware, we compare
      results generated using representative Nvidia GPGPUs from three recent
      generations: Fermi (C2075), Kepler (K20c), and Maxwell (GTX980). We explore
      scaling by solving the same boundary value problem (an extension-inflation test
      on a segment of human aorta) with progressively larger FE meshes. Our results
      demonstrate substantial improvements in simulation speeds relative to two
      benchmark FE codes (up to 300[Formula: see text] while maintaining accuracy), and
      thus open many avenues to novel applications in biomechanics and medicine.

PMID- 29199499
TI  - A nutritional evaluation of various typical Italian breakfast products: a
      comparison of macronutrient composition and glycaemic index values.
AB  - Breakfast foods with lower glycaemic responses are associated with better body
      weight control. Glycaemic index (GI) values of some commonly consumed breakfast
      foods in Italy were determined and compared, along with macronutrients.
      Cakes/pastries were low-medium GI (44-60), with high-sugar and saturated fat and
      low-fibre. Generally, mueslis and breads were medium GI (62-66 and 59-76,
      respectively) with higher fibre and lower saturated fat and sugar. The addition
      of spreads to bread lowered GI (47-66) but increased sugar and saturated fat.

PMID- 29199500
TI  - Management of a rare case of posterior condylar canal dural arteriovenous fistula
      presenting with subarachnoid haemorrhage: A case report and review of literature.
AB  - Posterior condylar canal dural arteriovenous fistula (PCC dAVF) is a rare entity
      with only three cases having been reported so far in the English literature. We
      describe the clinical presentation, imaging, and endovascular management of an
      elderly man with left PCC dAVF presenting with subarachnoid haemorrhage (SAH).
      Endovascular management of such cases requires thorough understanding of the
      vascular anatomy around the craniovertebral junction (CVJ) and variable bridging
      vein draining patterns. The fistula in our case was fed by the posterior
      meningeal branch of the left vertebral artery and was draining through a dilated
      and tortuous medullary bridging vein into the antero-lateral pontomedullary
      venous system. Transarterial glue embolisation was performed with complete
      exclusion of the fistula and venous pouches. The patient developed intractable
      hiccough and left-sided facial pain on the second post-procedural day, and MRI
      showed focal diffusion restriction in the left dorso-lateral medulla. He
      recovered completely after a short course of steroids.

PMID- 29199501
TI  - Older Adults Driving Under the Influence: Associations With Marijuana Use,
      Marijuana Use Disorder, and Risk Perceptions.
AB  - Despite increasing marijuana use among the 50+ age group, little research has
      been done on marijuana's impact on older adults' driving under the influence
      (DUI). Using the 2013 to 2014 National Survey on Drug Use and Health data, this
      study examined the association of older adults' self-reported DUI with marijuana
      use, marijuana abuse/dependence, and marijuana risk perception. The findings show
      that one third of past-year marijuana users aged 50+ reported past-year DUI, two
      thirds of which involved drugs. Those with marijuana abuse/dependence were 2.6
      times more likely than those without the disorder to report DUI, controlling for
      alcohol abuse/dependence, other illicit drug use, and sociodemographic and
      health/mental health statuses. As safe driving is key to prolonging independence
      in late life, clinicians need to educate older adults about the risk of marijuana
      use, alone and with other substances, on their driving capacity and provide age
      appropriate treatment for marijuana use disorder.

PMID- 29199502
TI  - ADHD Among Offenders: Prevalence and Relationship With Psychopathic Traits.
AB  - OBJECTIVE: Longitudinal studies have shown a strong association between ADHD and
      criminal behavior. The aims of this study were to examine the prevalence of adult
      ADHD in a high-security facility and to investigate the relationship between ADHD
      symptoms and psychopathic traits in criminal offenders. MATERIAL AND METHODS:
      Participants were recruited between October 2015 and January 2016 among the
      inmates from a high-security all-male correctional facility in Portugal. Self
      report scales were used to measure ADHD symptoms, current psychopathology, and
      psychopathic traits. An interview was conducted to collect sociodemographic data,
      along with information about adverse childhood experiences, substance use, and
      criminal record. The statistical analysis was conducted using STATA 13 with the
      significance level set at .05. RESULTS: From the final sample of 101 male
      prisoners, 17 participants (16.8%) screened positive for ADHD. Participants
      positive for ADHD had higher levels of general psychopathology and psychopathic
      traits. Psychopathic traits remained significantly higher in ADHD offenders after
      controlling for age, substance abuse, and early childhood adversities (OR = 1.07,
      p = .002) and this was explained by differences in the Meanness subscale (OR =
      1.11, p = .013). DISCUSSION/CONCLUSIONS: The present study shows that ADHD
      symptoms are highly prevalent among offenders and might have a modulating effect
      on the course of delinquent behavior. The cross-sectional association between
      ADHD symptoms and psychopathic traits reinforces the previously documented
      correlation between these disorders and can lead to a better understanding of the
      prevalent criminal behavior in ADHD patients.

PMID- 29199503
TI  - SMART Arm Training With Outcome-Triggered Electrical Stimulation in Subacute
      Stroke Survivors With Severe Arm Disability: A Randomized Controlled Trial.
AB  - BACKGROUND: Stroke survivors with severe upper limb disability need opportunities
      to engage in task-oriented practice to achieve meaningful recovery. OBJECTIVE: To
      compare the effect of SMART Arm training, with or without outcome-triggered
      electrical stimulation to usual therapy, on arm function for stroke survivors
      with severe upper limb disability undergoing inpatient rehabilitation. METHODS: A
      prospective, multicenter, randomized controlled trial was conducted with 3
      parallel groups, concealed allocation, assessor blinding and intention-to-treat
      analysis. Fifty inpatients within 4 months of stroke with severe upper limb
      disability were randomly allocated to 60 min/d, 5 days a week for 4 weeks of (1)
      SMART Arm with outcome-triggered electrical stimulation and usual therapy, (2)
      SMART Arm alone and usual therapy, or (3) usual therapy. Assessment occurred at
      baseline (0 weeks), posttraining (4 weeks), and follow-up (26 and 52 weeks). The
      primary outcome measure was Motor Assessment Scale item 6 (MAS6) at posttraining.
      RESULTS: All groups demonstrated a statistically ( P < .001) and clinically
      significant improvement in arm function at posttraining (MAS6 change >=1 point)
      and at 52 weeks (MAS6 change >=2 points). There were no differences in
      improvement in arm function between groups (P = .367). There were greater odds of
      a higher MAS6 score in SMART Arm groups as compared with usual therapy alone
      posttraining (SMART Arm stimulation generalized odds ratio [GenOR] = 1.47, 95%CI
      = 1.23-1.71) and at 26 weeks (SMART Arm alone GenOR = 1.31, 95% CI = 1.05-1.57).
      CONCLUSION: SMART Arm training supported a clinically significant improvement in
      arm function, which was similar to usual therapy. All groups maintained gains at
      12 months.

PMID- 29199504
TI  - Hospital Readmissions Reduction Program: Intended and Unintended Effects.
AB  - This study examines whether the Hospital Readmissions Reduction Program (HRRP),
      which penalizes hospitals with excess readmissions for certain conditions, has
      reduced hospital readmissions and led to unintended consequences. Our analyses of
      Florida hospital administrative data between 2008 and 2014 find that the HRRP
      resulted in a reduction in the likelihood of readmissions by 1% to 2% for
      traditional Medicare (TM) beneficiaries with heart failure, pneumonia, or chronic
      obstructive pulmonary disease. Readmission rates for Medicare Advantage (MA)
      beneficiaries and privately insured patients with heart attack and heart failure
      decreased even more than TM patients with the same target condition (e.g., for
      heart attack, the likelihood for TM beneficiaries to be remitted is 2.2% higher
      than MA beneficiaries and 2.3% higher than privately insured patients). We do not
      find any evidence of cost-shifting, delayed readmission, or selection on
      discharge disposition or patient income. However, the HRRP reduced the likelihood
      of Hispanic patients with target conditions being admitted by 2% to 4%.

PMID- 29199505
TI  - Development of a flowchart for risk assessment and allocation of preparation of
      monoclonal antibodies.
AB  - Monoclonal antibodies have expanded as a novel class of therapeutic agents. In
      contrast to appropriate guidelines for safe handling of cytotoxics, there are no
      real standards for the safe handling of monoclonal antibodies. Many questions
      have arisen whether monoclonal antibodies have to be prepared under controlled
      circumstances or can be prepared on the ward. We developed a flowchart which
      provides recommendations for the classification of monoclonal antibodies
      according to their toxicity profile and takes practical and financial issues into
      account. It allows oncology pharmacists worldwide to define which monoclonal
      antibodies can/must be prepared in pharmacy aseptic facilities and which
      monoclonal antibodies can be prepared on the ward.

PMID- 29199506
TI  - Inadequate response to imatinib treatment in chronic myeloid leukemia due to a
      drug interaction with phenytoin.
AB  - Imatinib mesylate and the newer BCR-ABL tyrosine kinase inhibitors are the
      standard therapy for chronic myeloid leukemia. Although these are remarkably
      effective drugs, some mechanisms of resistance have been identified including
      drug-to-drug interactions. Here we present the case of a chronic myeloid leukemia
      patient with an inadequate response to imatinib due to concurrent phenytoin
      administration. Conspicuously low imatinib plasma trough levels were documented.
      Imatinib dose was increased from 400 to 800 mg with good response. In conclusion,
      drug-to-drug interactions should be ruled out in cases of resistance to tyrosine
      kinase inhibitor treatment. Potent inducers of cytochrome P450 isoenzyme CYP3A4,
      as phenytoin, could induce inadequate responses due to increased imatinib
      clearance and low imatinib trough plasma levels. Thus, this interaction should be
      avoided. When this is not possible, dose escalation of imatinib and measurement
      of plasma levels, if available, is recommended.

PMID- 29199507
TI  - Asymmetric oculomotor apraxia, optic ataxia, and simultanagnosia with right
      hemispatial neglect from a predominantly left-sided lesion of the parieto
      occipital area.
AB  - INTRODUCTION: Balint's syndrome involves bilateral damage to the parieto
      occipital area. The extent of the effect of unilateral damage on the Balint's
      triad (oculomotor apraxia, optic ataxia, and simultanagnosia) remains unknown.
      METHODS: We examined a 63-year-old, right-handed woman who developed right
      hemianopia, oculomotor apraxia, optic ataxia, simultanagnosia, and hemispatial
      neglect (HSN) for the right after a cerebral infarction, with detailed
      neuropsychological tests, magnetic resonance imaging, and single photon emission
      computed tomography (SPECT). RESULTS: Neuropsychological examination showed that
      oculomotor apraxia, optic ataxia, and simultanagnosia were more pronounced in the
      right hemi-space, probably due to the limited eye movement in the right visual
      field, whereas HSN was restricted to the right hemi-space. Diffusion-weighted MR
      images revealed hyperintensity in the left parieto-temporo-occipital region, and
      several spotty areas of the bilateral frontal and parietal subcortical regions.
      SPECT revealed hypoperfusion in the left parieto-occipital region and frontal
      operculum and small areas of the right superior parietal lobule. CONCLUSIONS: The
      case suggests that asymmetric (more pronounced in the right hemi-space)
      oculomotor apraxia, optic ataxia, and simultanagnosia occur in an extensive
      lesion of the left parieto-occipital cortices. Although HSN is not a prerequisite
      for simultanagnosia, the coexistence of HSN aggravates simultanagnosia in the
      hemi-space opposite the lesion.

PMID- 29199508
TI  - Wrist inflammation: a retrospective comparison between septic and non-septic
      arthritis.
AB  - : This study aims to identify differences in demographics, clinical and
      laboratory data between wrist septic arthritis and non-septic arthritis in
      patients admitted for wrist inflammation. A retrospective review of inpatients
      from May 2012 to April 2015 was conducted. Seventy-seven patients were included.
      Non-septic arthritis patients were more likely to have chronic kidney disease,
      pre-existing gout, or both. All septic arthritis patients had normal serum uric
      acid levels, and two or more raised inflammatory markers (white cell count, C
      reactive protein, erythrocyte sedimentation rate). In patients with isolated
      wrist inflammation, the mean C-reactive protein in the septic arthritis group was
      significantly higher compared with the non-septic arthritis group (mean
      difference 132 mg/L, 95% CI 30.9-234). In this study, polyarticular involvement
      did not exclude a septic cause; nor did it imply a non-septic aetiology. Diabetic
      or immunosuppressed patients were not more likely to develop septic arthritis.
      The presence of chondrocalcinosis on wrist radiographs was virtually diagnostic
      of non-septic arthritis. LEVEL OF EVIDENCE: IV.

PMID- 29199509
TI  - Carpometacarpal joint flexion view to better visualize base of proximal phalanges
      of ulnar digits.

PMID- 29199510
TI  - Regulation of RhoA GTPase and novel target proteins for ROCK.
AB  - Rho GTPases play significant roles in cellular function and their activity is
      regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating
      proteins (GAPs), providing activation and inactivation of these GTPases,
      respectively. Active GTP-bound form of RhoA activates its effector proteins while
      the inactive GDP-bound form of RhoA exists in a RhoA-RhoGDI (guanine nucleotide
      dissociation inhibitor) complex in the cytosol. In particular, IkappaB kinase
      gamma IKKgamma/NF-kappaB essential modulator (NEMO) plays a role as a GDI
      displacement factor (GDF) for RhoA activation through binding to RhoA-RhoGDI
      complex. Meanwhile, prion protein inactivates RhoA despite RhoA/RhoGDI
      association. Novel target proteins for Rho-associated kinase (ROCK) such as
      glycogen synthase kinase (GSK)-3beta and IKKbeta are recently discovered. Here,
      we elaborate on a post-translationally modified version of RhoA, phosphorylated
      at Tyr42 and oxidized at Cys16/20. This form of RhoA dissociates from RhoA-RhoGDI
      complex and activates IKKbeta on IKKgamma/NEMO, thus providing possibly a
      critical role for tumourigenesis.

PMID- 29199511
TI  - Clonogenic versus morphogenic mutations in myeloid neoplasms: chronologic
      observations in a U2AF1, TET2, CSF3R and JAK2 'co-mutated' myeloproliferative
      neoplasm suggest a hierarchical order of mutations and potential predictive value
      for kinase inhibitor treatment response.

PMID- 29199512
TI  - Long-term renal and overall survival of critically ill patients with acute renal
      injury who received continuous renal replacement therapy.
AB  - BACKGROUND: Acute kidney injury (AKI) is associated with the increased short-term
      mortality of critically ill patients on continuous renal replacement therapy
      (CRRT). The aim of this research was to evaluate the association of kidney
      function at discharge with the long-term renal and overall survival of critically
      ill patients with AKI who were on CRRT in an intensive care unit (ICU). METHODS:
      We retrospectively collected data for critically ill patients with AKI who were
      admitted to ICU on CRRT at a tertiary metropolitan hospital in China between 2008
      and 2013. The patients were followed up to their death or to 30 September 2016 by
      telephone. RESULTS: A total of 403 patients were enrolled in this study. The 1-,
      3- and 5-year patient survival rates were 64.3 +/- 2.4, 55.8 +/- 2.5 and 46.3 +/-
      2.7%, respectively. In multivariate analysis, age, sepsis, decreased renal
      perfusion (including volume contraction, congestive heart failure, hypotension
      and cardiac arrest), preexisting kidney disease, Apache II score, Saps II score,
      vasopressors and eGFR <45 mL/min/1.73 m2 at discharge were independent factors
      for worse long-term patient survival. And age, preexisting kidney disease, Apache
      II score, mechanical ventilation (MV) and eGFR <45 mL/min/1.73 m2 at discharge
      were also associated with worse renal survival. CONCLUSIONS: This study showed
      that impaired kidney function at discharge was shown to be an important risk
      factor affecting the long-term renal survival rates of critically ill patients
      with AKI. An eGFR <45 mL/min/1.73 m2 was an independent risk factor for decreased
      overall survival and renal survival.

PMID- 29199513
TI  - Paraneoplastic cerebellar syndromes associated with antibodies against Purkinje
      cells.
AB  - The paraneoplastic cerebellar syndrome presents as severe neuroimmunological
      disease associated with malignancies. Antibodies against antigens expressed by
      tumor cells cross-react with proteins of cerebellar Purkinje cells leading to
      neuroinflammation and neuronal loss. These antineuronal antibodies are
      preferentially investigated by serological analyses while examination of the
      cerebrospinal fluid is only performed infrequently. We retrospectively
      investigated 12 patients with antineuronal antibodies against Purkinje cells with
      a special focus on cerebrospinal fluid. Our results confirm a subacute disease
      with a severe cerebellar syndrome in 10 female patients due to anti-Yo antibodies
      associated mostly with gynecological malignancies. While standard cerebrospinal
      fluid parameters infrequently revealed pathological results, all patients
      presented oligoclonal bands indicating intrathecal IgG synthesis. Analyses of
      anti-Yo antibodies in cerebrospinal fluid by calculating the antibody specific
      index revealed intrathecal synthesis of anti-Yo antibodies in these patients. In
      analogy to anti-Yo syndrome, an intrathecal production of anti-Tr antibodies in
      one patient who presented with a paraneoplastic cerebellar syndrome was detected.
      In an additional patient, anti-Purkinje cell antibodies of unknown origin in the
      cerebrospinal fluid but not in serum were determined suggesting an isolated
      immune reaction within the central nervous system (CNS) and underlining the
      importance of investigating the cerebrospinal fluid. In conclusion, patients with
      a cerebellar syndrome display a distinct immune reaction within the cerebrospinal
      fluid including intrathecal synthesis of disease-specific antibodies. We
      emphasize the importance of a thorough immunological work up including
      investigations of both serum and cerebrospinal fluid.

PMID- 29199515
TI  - The future role of pharmacogenomics in anticancer agent-induced cardiovascular
      toxicity.

PMID- 29199516
TI  - The role of ERK and Smad2 signal pathways in the alternatively activated
      macrophages induced by TGF-beta1 and high-ambient glucose.
AB  - Macrophages can be alternatively activated by TGF-beta1 and high-ambient glucose,
      in which the role of Smad2 and the crosstalk between ERK and Smad2 pathways are
      not fully understood. The activation of ERK and Smad2 pathways and the expression
      of arginase-1 were detected by Western blot. The role of Smad2 and the
      relationship between ERK and Smad2 pathways were investigated by using
      biochemical inhibitors. The protein of arginase-1 was significantly overexpressed
      in RAW264.7 cells stimulated by TGF-beta1 and high-ambient glucose, which can be
      partially blocked by not only U0126 (ERK inhibitor) but also SB431542 (Smad2
      inhibitor). Furthermore, simply inhibiting one pathway had no effect on the other
      pathway. In conclusion, both ERK and Smad2 signal pathways are involved in the
      activation of macrophages induced by TGF-beta1 and high-ambient glucose, while
      there is no crosstalk shown in the process.

PMID- 29199514
TI  - RNA polymerases IV and V influence the 3' boundaries of Polymerase II
      transcription units in Arabidopsis.
AB  - Nuclear multisubunit RNA polymerases IV and V (Pol IV and Pol V) evolved in
      plants as specialized forms of Pol II. Their functions are best understood in the
      context of RNA-directed DNA methylation (RdDM), a process in which Pol IV
      dependent 24 nt siRNAs direct the de novo cytosine methylation of regions
      transcribed by Pol V. Pol V has additional functions, independent of Pol IV and
      24 nt siRNA biogenesis, in maintaining the repression of transposons and genomic
      repeats whose silencing depends on maintenance cytosine methylation. Here we
      report that Pol IV and Pol V play unexpected roles in defining the 3' boundaries
      of Pol II transcription units. Nuclear run-on assays reveal that in the absence
      of Pol IV or Pol V, Pol II occupancy downstream of poly A sites increases for
      approximately 12% of protein-coding genes. This effect is most pronounced for
      convergently transcribed gene pairs. Although Pols IV and V are detected near
      transcript ends of the affected Pol II - transcribed genes, their role in
      limiting Pol II read-through is independent of siRNA biogenesis or cytosine
      methylation for the majority of these genes. Interestingly, we observed that
      splicing was less efficient in pol IV or pol V mutant plants, compared to wild
      type plants, suggesting that Pol IV or Pol V might affect pre-mRNA processing. We
      speculate that Pols IV and V (and/or their associated factors) play roles in Pol
      II transcription termination and pre-mRNA splicing by influencing polymerase
      elongation rates and/or release at collision sites for convergent genes.

PMID- 29199517
TI  - Determinants of variable resource use for multidisciplinary team meetings in
      cancer care.
AB  - BACKGROUND: Multidisciplinary team meetings (MDTMs) have developed into standard
      of care to provide expert opinion and to grant evidence-based recommendations on
      diagnostics and treatment of cancer. Though MDTMs are associated with a range of
      benefits, a growing number of cases, complex case discussion and an increasing
      number of participants raise questions on cost versus benefit. We aimed to
      determine cost of MDTMs and to define determinants hereof based on observations
      in Swedish cancer care. METHODS: Data were collected through observations of 50
      MDTMs and from questionnaire data from 206 health professionals that participated
      in these meetings. RESULTS: The MDTMs lasted mean 0.88 h and managed mean 12.6
      cases with mean 4.2 min per case. Participants were mean 8.2 physicians and 2.9
      nurses/other health professionals. Besides the number of cases discussed, meeting
      duration was also influenced by cancer diagnosis, hospital type and use of video
      facilities. When preparatory work, participation and post-MDTM work were
      considered, physicians spent mean 4.1 h per meeting. The cost per case discussion
      was mean 212 (range 91-595) EUR and the cost per MDTM was mean 2675 (range 1439
      4070) EUR. CONCLUSIONS: We identify considerable variability in resource use for
      MDTMs in cancer care and demonstrate that 84% of the total cost is derived from
      physician time. The variability demonstrated underscores the need for regular and
      structured evaluations to ensure cost effective MDTM services.

PMID- 29199518
TI  - Improvement on upper limb body-powered prostheses (1921-2016): A systematic
      review.
AB  - Body-powered prostheses are known for their advantages of cost, reliability,
      training period, maintenance, and proprioceptive feedback. This study primarily
      aims to analyze the work related to the improvement of upper limb body-powered
      prostheses prior to 2016. A systematic review conducted via the search of the Web
      of Science electronic database, Google Scholar, and Google Patents identified 155
      papers from 1921 to 2016. Sackett's initial rules of evidence were used to
      determine the levels of evidence, and only papers categorized in the design and
      development category and patents were analyzed. A total of 40 papers in the sixth
      level of "Design and Development" of an upper limb body-powered prosthesis were
      found. Approximately 81% were categorized under mechanical alteration. Most
      papers were patent-type documents (48%), with the Journal of Rehabilitation
      Research and Development publishing most of the articles related to the design
      and development of body-powered prostheses. Papers in the scope of the study were
      published once every 3 years in almost a century, proving that only a few studies
      were conducted to improve body-powered arms compared with myoelectric technology.
      Further research should be carried out mainly in areas that have received less
      attention.

PMID- 29199519
TI  - Outcomes of DA-EPOCH-R induction plus autologous transplant consolidation for
      double hit lymphoma.
AB  - High-grade B cell lymphoma with MYC and BCL2 rearrangements (double hit) has a
      poor prognosis with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin,
      vincristine, prednisone). We report here a treatment algorithm of DA-EPOCH-R
      (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,
      rituximab) followed by BEAM (carmustine, etoposide, cytarabine, melphalan)
      autologous transplant in 36 cases of previously untreated double hit lymphoma
      (DHL) from 2010 to 2015. A high risk International Prognostic Index (IPI) was
      present in 42% of cases. At median follow-up of 38 months, the 2-year progression
      free survival (PFS) and overall survival (OS) were 69% (95% CI 54-84%) and 71%
      (95% CI 56-86%). Eight cases were refractory to induction with 1-year OS 20%, and
      no factors were predictive for primary refractory disease. Of 28 responders, 17
      proceeded to transplant while 11 were observed, primarily due to age and co
      morbidities. By 24-week landmark analysis after diagnosis, the 2-year PFS and OS
      were both 94% (95% CI 83-100%) vs 79% (95% CI 52-100%) for transplant vs
      observation (p = .59 for both PFS and OS). There was no significant benefit to
      consolidative transplant in our series, and primary refractory DHL needs novel
      approaches.

PMID- 29199520
TI  - The Trauma Resiliency Model: A "Bottom-Up" Intervention for Trauma Psychotherapy.
AB  - BACKGROUND: The Trauma Resiliency Model (TRM) is an innovative therapeutic
      approach for trauma. This "bottom-up" somatic approach comprises nine skills that
      use sensory awareness for emotion regulation and integration. Body-based
      therapies may be more effective for trauma than currently used cognitive ('top
      down") and exposure therapies. OBJECTIVE: The purpose of this article is to
      present TRM and current literature on the neuroscience of trauma and resiliency,
      and the rationale for body-based therapy. Two case examples illustrate the
      practical use of TRM therapy. DESIGN: The literature on the neuroscience of
      trauma, resiliency, and somatic approaches in therapy is reviewed. RESULTS: TRM
      teaches the biology of trauma responses and the practice of emotion regulation
      through biologically based skills. Neuroscience theory supports somatic awareness
      models; however, research on somatic therapies is limited. CONCLUSIONS: Chronic
      distress from trauma derails the ability to live life resiliently. TRM addresses
      trauma processing in a gentle and invitational manner and is a novel departure
      from existing therapies. Despite a paucity of research on body-based therapy,
      these therapies have strong neurophysiologic underpinnings.

PMID- 29199521
TI  - Electronic Nicotine Delivery Systems (ENDS): What Nurses Need to Know.
AB  - BACKGROUND: Efforts to decrease adverse effects of tobacco use are affected by
      emergence of new nicotine delivery products. Advertising, product promotion, and
      social media promote use of these products, yet a lack of evidence regarding
      safety leaves nurses unprepared to counsel patients. OBJECTIVES: To critically
      evaluate current research, reviews of literature, expert opinion, and stakeholder
      policy proposals on use and safety of electronic nicotine delivery systems
      (ENDS). DESIGN: A targeted examination of literature generated by key
      stakeholders and subject matter experts was conducted using key words, modified
      by risk factors, and limited to the past 8 years. RESULTS: Current knowledge gaps
      in research literature and practice implications of the literature are discussed.
      CONCLUSIONS: The safety of ENDS is questionable and unclear. There are clear
      health risks of nicotine exposure to developing brains. Potential health risks of
      ENDS secondhand emissions exposure exist. Using ENDS to facilitate total tobacco
      cessation is not proven.

PMID- 29199522
TI  - Use of outcome measurements in clinical practice: How specific should one be?
AB  - OBJECTIVE: Progress feedback is often measured with generic instruments that
      measure common symptoms and generic aspects of functioning. The current study
      aims to explore the relative usefulness of disorder-specific measures. We
      hypothesized that disorder-specific instruments reveal more improvement than
      generic instruments and that the addition of disorder-specific instruments
      results in better treatment outcomes. METHOD: We used a cohort of 3419 patients
      with a depression. As generic measures, we used the BSI or the symptoms distress
      subscale of the OQ-45. In 946 patients, a specific instrument, the IDS-SR, was
      added. We compared mean change scores and percentages of clinical significant
      change. In a matched case control design, we analyzed whether the additional use
      of the IDS-SR resulted in better treatment outcomes. RESULTS: Mean change scores
      of both types of instruments were comparable. When comparing clinical significant
      change, agreement was moderate. We found better outcomes on the generic
      instruments when both a generic and a disorder-specific instrument were used.
      CONCLUSION: In individual treatment of depression, generic and disorder-specific
      instruments are not interchangeable. The additional use of disorder-specific
      instruments provides a more complete picture of the patient's progress than the
      use of a generic instrument alone. Clinical or methodological significance of
      this article: In outcome management often rather generic instruments are used,
      that do not address the specific symptoms of the primary diagnosis of patients.
      In daily practice clinicians do not always use the feedback on treatment
      progress, when they perceive the feedback as not specific or relevant enough. The
      current study aims to explore the relative usefulness of measures that focus on
      symptoms that characterize the primary diagnosis of patients with a depression
      compared to the generic measures. We used a large cohort of existing data of
      patients of several mental health care organizations that share an application
      for outcome measurement. First, we compared outcomes of generic instruments and a
      disorder-specific instrument of a subsample of patients with a depressive
      disorder that completed both kinds of instruments. Next, we applied a matched
      case control design to control for differences between patients and analyzed
      whether the additional use of disorder-specific instruments predicted better
      outcomes. With this methodology, we tried to optimize both the methodological
      quality as well as the clinical significance of our research.

PMID- 29199523
TI  - Functional shoulder ratios with high velocities of shoulder internal rotation are
      most sensitive to determine shoulder rotation torque imbalance: a cross-sectional
      study with elite handball players and controls.
AB  - The aim of the present study was to determine which approach to calculating
      shoulder ratios is the most sensitive for determining shoulder torque imbalance
      in handball players. Twenty-six participants (handball athletes, n = 13; healthy
      controls, n = 13) performed isokinetic concentric and eccentric shoulder internal
      rotation (IR) and external rotation (ER) assessment at 60, 180 and 300 degrees
      /s. We used eight approaches to calculating shoulder ratios: four concentric
      (i.e. concentric ER torque divided by concentric IR torque), and four functional
      (i.e. eccentric ER torque divided by concentric IR torque) at the velocities of
      60, 180 and 300 degrees /s for both IR and ER, and combining 60 degrees /s of ER
      and 300 degrees /s of IR. A three factorial ANOVA (factors: shoulder ratios,
      upper limb sides, and groups) along with Tukey's post-hoc analysis, and effect
      sizes were calculated. The findings suggested the functional shoulder ratio
      combining 60 degrees /s of ER and 300 degrees /s of IR is the most sensitive to
      detect differences between upper limbs for handball players, and between players
      and controls for the dominant side. The functional shoulder ratio combining 60
      degrees /s of ER with 300 degrees /s of IR seems to present advantages over the
      other approaches for identifying upper limb asymmetries and differences in
      shoulder torque balance related to throwing.

PMID- 29199524
TI  - Metal complexes of naphthoquinone based ligand: synthesis, characterization,
      protein binding, DNA binding/cleavage and cytotoxicity studies.
AB  - Protein binding, DNA binding/cleavage and in vitro cytotoxicity studies of 2-((3
      (dimethylamino)propyl)amino)naphthalene-1,4-dione (L) and its four coordinated
      M(II) complexes [M(II) = Co(II), Cu(II), Ni(II) and Zn(II)] have been
      investigated using various spectral techniques. The structure of the ligand was
      confirmed by spectral and single crystal XRD studies. The geometry of the
      complexes has been established using analytical and spectral investigations.
      These complexes show good binding tendency to bovine serum albumin (BSA)
      exhibiting high binding constant values (105 M-1) when compared to free ligand.
      Fluorescence titration studies reveal that these compounds bind strongly with CT
      DNA through intercalative mode (Kapp 105 M-1) and follow the order: Cu(II) >
      Zn(II) > Ni(II) > Co(II) > L. Molecular docking study substantiate the strength
      and mode of binding of these compounds with DNA. All the complexes efficiently
      cleaved pUC18-DNA via hydroxyl radical mechanism and the Cu(II) complex degraded
      the DNA completely by converting supercoiled form to linear form. The complexes
      demonstrate a comparable in vitro cytotoxic activity against two human cancer
      cell lines (MCF-7 and A-549), which is comparable with that of cisplatin. AO/EB
      and DAPI staining studies suggest apoptotic mode of cell death, in these cancer
      cells, with the compounds under investigation.

PMID- 29199525
TI  - Molecular genetic profile in BCR-ABL1 negative pediatric B-cell acute
      lymphoblastic leukemia can further refine outcome prediction in addition to that
      by end-induction minimal residual disease detection.
AB  - The recently proposed molecular genetic criteria promise improved risk-prediction
      in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility
      in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction
      minimal residual disease (MRD). The DNA was analyzed for copy number alterations
      in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with median age 7
      years (2 months-18 years) included MRD-positive (24; 32%), and MRD negative
      standard (20; 26%), intermediate (20; 26%), & high risk (12;16%) cases. The risk
      classification was based on age, initial total leukocyte count, central nervous
      system involvement, cytogenetics, day 8 prednisolone response and MRD status
      after induction chemotherapy. The genetic profile based on Moorman's criteria
      identified two subgroups with different event free survival (EFS) (0.77 vs. 0.38;
      p = .045) and overall survival (OS) (0.90 vs. 0.30; p = .037) in the MRD-negative
      intermediate-risk group. The genetic profile also separated two subgroups with
      different EFS (0.75 vs. 0.41; p = .036) in the MRD-positive group, however the OS
      was not different (0.75 vs. 0.57; p = .293).

PMID- 29199526
TI  - The relationship between mother and infant plasma trace element and heavy metal
      levels and the risk of neural tube defect in infants.
AB  - OBJECTIVE: To determine levels of trace elements [copper (Cu), zinc (Zn),
      selenium (Se), and cobalt (Co)] and heavy metals [arsenic (As), mercury (Hg),
      lead (Pb), and cadmium (Cd)] in the plasma of mothers and infants and investigate
      the relationship between those levels and neural tube defects (NTD). METHODS: A
      total of 100 neonates diagnosed with NTD and placed in the Neonatal Intensive
      Care Unit of Yuzuncu Yil University, Turkey between May 2013 and December 2016
      comprised the study group. The control group consisted of 70 healthy neonates not
      diagnosed with NTD or any other congenital anomalies. For both the groups, mother
      and infant plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and
      compared. Plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and
      compared between two groups of mothers and infants. FINDINGS: Mother and infant
      plasma levels of trace elements Zn and Se were determined to be significantly
      lower in the study group compared with the control group, while Cu levels were
      significant elevated in the study group (all p values < .05). Plasma levels of
      heavy metals As, Pb, and Cd were found to be significantly higher in the NTD
      control group (p < .05 for all). There was no association between maternal
      infection, maternal smoking status, history of miscarriage, or history of NTD
      with the development of NTD (p > .05). Differences in maternal age, birth weight,
      length of gestation, and infant gender for the two groups were also determined
      not to be statistically significant. RESULTS: High plasma levels of heavy metals
      As, Pb, and Cd and trace element Cu were identified as risk factors for the
      development of NTD. At the same time, low plasma levels of trace elements Zn and
      Se were also found to be risk factors for NTD. However, no association between Hg
      and Co plasma levels and increased risk for the development of NTD was observed.
      This study, while being the most comprehensive case study to date investigating
      the relationship between heavy metals and trace element levels and increased risk
      of NTD, nonetheless highlights the need for further research in order to make
      definite statements regarding this relationship.

PMID- 29199527
TI  - Diversity in clinical manifestations and imaging features of neurosyphilis:
      obstacles to the diagnosis and treatment (report of three cases).
AB  - OBJECTIVE: To explore the clinical manifestations and imaging features of
      neurosyphilis and to discuss the obstacles in the diagnosis and treatment of
      neurosyphilis. METHODS: We present this case study involving three cases of
      definite neurosyphilis, focusing on their clinical data. RESULTS: Case 1 is a
      patient with numb and weak left lower limb. Case 2 showed slow reaction and
      dementia behaviors including worse memory and the decrease of calculation and
      orientation ability in this patient. Case 3 is a peripheral incomplete left
      oculomotor nerve palsy patient. Magnetic resonance imaging findings of three
      patients are different. And single photon emission computed tomography showed the
      regional cerebral blood flow was all hypoperfused. There were some difficulties
      in diagnosing and treating the patients in these three cases. CONCLUSION: The
      clinical manifestations and imaging findings of neurosyphilis are diverse.
      Clinicians should pay attention to neurosyphilis. After clear diagnosis, patients
      would receive norm treatment in time.

PMID- 29199528
TI  - Gene networks associated with non-syndromic intellectual disability.
AB  - Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous
      disorder, with more than 200 candidate genes to date. Despite the increasing
      number of novel mutations detected, a relatively low number of recurrently
      mutated genes have been identified, highlighting the complex genetic architecture
      of the disorder. A systematic search of PubMed and Medline identified 245 genes
      harbouring non-synonymous variants, insertions or deletions, which were
      identified as candidate NS-ID genes from case reports or from linkage or pedigree
      analyses. From this list, 33 genes are common to syndromic intellectual
      disability (S-ID) and 58 genes are common to certain neurological and
      neuropsychiatric disorders that often include intellectual disability as a
      clinical feature. We examined the evolutionary constraint and brain expression of
      these gene sets, and we performed gene network and protein-protein interaction
      analyses using GeneGO MetaCoreTM and DAPPLE, respectively. The 245 NS-ID
      candidate genes were over-represented in axon guidance, synaptogenesis, cell
      adhesion and neurotransmission pathways, all of which are key neurodevelopmental
      processes for the establishment of mature neuronal circuitry in the brain. These
      245 genes exhibit significantly elevated expression in human brain and are
      evolutionarily constrained, consistent with expectations for a brain disorder
      such as NS-ID that is associated with reduced fecundity. In addition, we report
      enrichment of dopaminergic and glutamatergic pathways for those candidate NS-ID
      genes that are common to S-ID and/or neurological and neuropsychiatric disorders
      that exhibit intellectual disability. Collectively, this study provides an
      overview and analysis of gene networks associated with NS-ID and suggests
      modulation of neurotransmission, particularly dopaminergic and glutamatergic
      systems as key contributors to synaptic dysfunction in NS-ID.

PMID- 29199529
TI  - "In the Sport I Am Here": Therapeutic Processes and Health Effects of Sport and
      Exercise on PTSD.
AB  - Current evidence suggests positive effects of exercise on posttraumatic stress
      symptoms; however, knowledge about how these effects are achieved is limited.
      Thus, this study aims to contribute to a more holistic understanding of these
      effects. We performed a single case study of a war and torture survivor, who was
      diagnosed with posttraumatic stress disorder (PTSD) and depression, and who was
      participant of the sport and exercise therapy program Movi Kune. Participant
      observation was conducted as well as semi-structured interviews with the
      participant and his psychotherapist. Data analysis resulted in the proposal of
      different processes: The focus on bodily sensations related to an exposure
      effect, contributing to improvements in body awareness, coping behavior, and
      affect regulation, whereas the focus on playing related to an improved
      performance, presence, enjoyment, and mastery experiences, pointing toward
      distraction and motivational-restorative effects. The findings also advice to be
      cautious as participants may be exposed to negative sensations and trauma-related
      triggers.

PMID- 29199530
TI  - Unspoken Playground Rules Discourage Adolescent Physical Activity in School: A
      Focus Group Study of Constructs in the Prototype Willingness Model.
AB  - The health benefits of exercise in school are recognized, yet physical activity
      continues to decline during early adolescence despite numerous interventions. In
      this study, we investigated whether the prototype willingness model, an account
      of adolescent decision making that includes both reasoned behavioral choices and
      unplanned responses to social environments, might improve understanding of
      physical activity in school. We conducted focus groups with British pupils aged
      12 to 13 years and used deductive thematic analysis to search for themes relating
      to the model. Participants described reasoned decisions about physical activity
      outside school and unplanned choices to be inactive during break, in response to
      social contexts described as more "judgmental" than in primary school. Social
      contexts appeared characterized by anxiety about competence, negative peer
      evaluation, and inactive playground norms. The prototype willingness model might
      more fully explain physical activity in school than reasoned behavioral models
      alone, indicating potential for interventions targeting anxieties about
      playground social environments.

PMID- 29199532
TI  - Translating Knowledge From a Family Systems Approach to Clinical Practice:
      Insights From Knowledge Translation Research Experiences.
AB  - While there has been continued growth in family nursing knowledge, the complex
      process of implementing and sustaining family nursing in health care settings
      continues to be a challenge for family nursing researchers and clinicians alike.
      Developing knowledge and skills about how to translate family nursing theory to
      practice settings is a global priority to make family nursing more visible. There
      is a critical need for more research methods and research evidence about how to
      best move family nursing knowledge into action. Enhancing health care practice is
      a multifactorial process that calls for a systemic perspective to ensure its
      efficacy and sustainability. This article presents insights derived from lessons
      learned through recent research experiences of using a knowledge translation
      model to promote practice changes in health care settings. These insights aim to
      optimize (a) knowledge translation of a Family Systems Approach (FSA) in practice
      settings; (b) knowledge translation research processes; and

PMID- 29199533
TI  - A purposeful Yet Nonimposing Approach: How Japanese Home Care Nurses Establish
      Relationships With Older Clients and Their Families.
AB  - Relationship development is crucial to nursing practice with families. However,
      little is known about the process of building relationships with multiple family
      members in home care settings and in various cultures. The objective of this
      study was to explore the experiences of home care nurses about how they
      established relationships with older clients and their families in Japan.
      Grounded theory was used to guide the research. Twenty-three expert home care
      nurses participated in semistructured interviews concerning their family nursing
      practice. The establishment of relationships with clients/family members was
      based on a purposeful yet nonimposing approach composed of four aspects: keeping
      a mindful distance from the family, not being a threat to family life, being a
      comfortable neighbor, and gaining trust as a competent nurse. Through a
      purposeful nonimposing approach, Japanese home care nurses promoted and nurtured
      nurse-family relationships and became involved in the life of the family. These
      findings provide a useful foundation to guide practice with families and grow
      knowledge about the process of establishing relationships with multiple family
      members in home settings.

PMID- 29199534
TI  - Tips for Developing a Successful Family Research Proposal.
AB  - Based on the authors' experiences conducting family research using varied
      methodological and conceptual approaches, the intent of this article is to offer
      practical advice for developing a successful research proposal that builds on
      existing work and makes a compelling case for the investigator's family focus,
      study design, and analytic approach. The article highlights key challenges unique
      to family research and offers suggestions and strategies for addressing the
      challenges.

PMID- 29199535
TI  - Journal of Family Nursing and Japanese Journal of Research in Family Nursing
      Collaboration 2017.

PMID- 29199537
TI  - Equine renal hemangiosarcoma: clinical presentation, pathologic features, and
      pSTAT3 expression.
AB  - Hemangiosarcoma is an uncommon tumor in horses. We characterized 3 cases of
      equine renal hemangiosarcoma, focusing on clinical and pathologic features, and
      describe occurrence of the epithelioid variant of hemangiosarcoma in one of these
      cases. Nuclear expression of phosphorylated STAT3 (pSTAT3) was assessed to
      analyze potential inappropriate STAT3 activation as a component of tumor
      pathogenesis. Clinical signs in the 3 horses included insidious weight loss,
      followed in one case by serosanguineous nasal discharge and terminal epistaxis,
      and nonspecific signs of abdominal pain. Two of the hemangiosarcomas had a
      classical histopathologic appearance; in the other, neoplastic cells were
      polygonal and were arranged in densely packed sheets, resembling the epithelioid
      variant. Cross-reactivity of a pSTAT3 antibody was established by demonstration
      of pSTAT3 expression in the epithelium of glabrous skin by immunoblotting and
      immunohistochemistry. In the epithelioid hemangiosarcoma, ~40% of neoplastic
      cells exhibited nuclear pSTAT3 expression, but in the other 2 cases, expression
      was weak and variable in the neoplastic population, although stromal cell pSTAT3
      activity was evident in pulmonary metastases in one case.

PMID- 29199538
TI  - The sooth beneath the taste roseas in the urethra and first description of neuro
      morpho-chemical mechanism of penile erectile posture in males: an experimental
      study.
AB  - AIM: The morphologic mechanism of orgasmic sensation has not yet been understood.
      Taste roseas may be stimulated by fructose via pudendal nerves, which has not
      been studied yet. METHODS: In this study, 27 male adult rabbits were used, which
      were divided into three groups: 5 as control; 5 as SHAM and 17 used as study
      group. We injected 0.2 cc of distilled water to SHAM and 0.2 cc of fructose
      solution to the study group of their urethral orifices, and examined the
      occurrence of penile erection. The relationship between erection and pudendal
      nerve ganglia and penile tissues was statistically compared. RESULTS: In animals
      with high neuron density of pudendal ganglia, more erection phenomenon was
      observed than those animals with low neuron density. Interestingly, neuron
      density of pudendal ganglia was 9.243 +/- 542 /mm3 in hypoactive and was 5.980 +/
      463 /mm3 in non-active animals (p < 0.05). CONCLUSIONS: The seminal fructose may
      stimulate taste roseas of the urethra and glans penis via pudendal nerves. The
      present study describes a new neuro-morpho-chemical mechanism of orgasmic
      sensation with its neurosurgical aspect.

PMID- 29199539
TI  - The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D)
      polymorphism is associated with worse functional outcome of ischaemic stroke.
AB  - PURPOSE: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be
      associated with the occurrence of ischaemic stroke through its effect on
      pathogenesis of atherosclerosis and hypertension. This study was aimed to examine
      the association between this polymorphism with functional outcome of ischaemic
      stroke. METHOD: This was a cross-sectional study. The subjects were patients with
      ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on
      demographic characteristics, stroke risk factors, comorbidities and stroke
      severity were assessed on admission. The functional outcome, Barthel index (BI),
      was assessed when the patients were discharged from the hospital. ACE I/D
      genotypes of the patients were identified by polymerase chain reaction (PCR).
      RESULT: In total, 61 patients were included. Of these, 38 patients (62.3%) had II
      polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD
      polymorphism in the ACE gene. There were significant differences in the
      functional outcomes between patients without D allele (II polymorphisms) and
      patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 +/-
      23.57 and 60.65 +/- 27.15, respectively; p = 0.034). Multiple linear regression
      model showed that the availability of D allele is an independent variable
      negatively associated with functional outcome as assessed by BI (beta = -0.232, p
      = 0.024). CONCLUSION: This study showed that the D allele in ACE I/D polymorphism
      is associated with worse functional outcomes. This highlights the possibility of
      further research to improve functional outcomes of ischaemic stroke by inhibiting
      the ACE system.

PMID- 29199540
TI  - Is the use of hydroxyethyl starch as priming solution during cardiac surgery
      advisable? A randomized, single-center trial.
AB  - INTRODUCTION: The use of cardiopulmonary bypass (CPB) leads to increased fluid
      filtration and edema. The use of artificial colloids to counteract fluid
      extravasation during cardiac surgery is controversial. Beneficial effects on
      global fluid loading, leading to better cardiac performance and hemodynamics,
      have been claimed. However, renal function and coagulation may be adversely
      affected, with unfavorable impact on outcome following cardiac surgery. METHODS:
      Forty patients were randomly allocated to study groups receiving either acetated
      Ringer's solution (CT group) or hydroxyethyl starch (HES group, Tetraspan(r)) as
      CPB priming solution. Fluid balance, bleeding and hemodynamics, including cardiac
      output, were followed postoperatively. The occurrence of acute kidney injury was
      closely registered. RESULTS: Two patients were excluded from further analyzes due
      to surgical complications. Fluid accumulation was attenuated in the HES group
      (3374 (883) ml) compared with the CT group (4328 (1469) ml) (p=0.024). The
      reduced perioperative fluid accumulation was accompanied by an increased cardiac
      index immediately after surgery (2.7 (0.4) L/min/m2 in the HES group and 2.1
      (0.3) L/min/m2 in the CT group (p<0.001)). No increase in bleeding could be
      demonstrated in the HES group. Three patients, all of them in the HES group,
      experienced acute kidney injury postoperatively. CONCLUSIONS: CPB priming with
      HES solution lowers fluid loading during bypass and improves cardiac function in
      the early postoperative period. The manifestation of acute kidney injury
      exclusively in the HES group of patients raises doubts about the use of HES
      products in conjunction with cardiac surgery. (
      https://clinicaltrials.gov/ct2/show/NCT01511120 ).

PMID- 29199541
TI  - Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary
      bypass in children with sevoflurane anesthesia.
AB  - BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia
      maintained by sevoflurane administered via the oxygenator is increasingly common.
      Anesthetic uptake and requirement may be influenced by the non-physiological
      conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may,
      therefore, be useful to guide the administration of sevoflurane during this
      phase. OBJECTIVE: The objective of this prospective, clinical, observational
      study was to assess the correlation between body temperature, Narcotrend Index
      (NI) and administered sevoflurane in children during CPB. METHODS: Forty-four
      children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied.
      On bypass, anesthesia was maintained with sevoflurane administered via the
      oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum
      alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10
      minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port
      via a separate connecting line and the MAC was measured by the agent analyzer of
      the anesthesia machine. RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values
      show that narcosis depth (as indicated by NI) can primarily be explained by the
      interaction of MAC and temperature. The analysis of variance (without the
      interaction term) confirms the significant and independent association of both
      factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI:
      0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced
      significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48). CONCLUSION:
      Perfusionists and anesthetists should be aware of the results of processed
      electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements
      differ inter-individually; they may decrease during cooling and increase during
      rewarming. Therefore, it seems reasonable to include the results of processed EEG
      monitoring when administering sevoflurane during CPB in children, but further
      studies are necessary to confirm this thesis.

PMID- 29199543
TI  - Genetic variations of the xenoreceptors NR1I2 and NR1I3 and their effect on drug
      disposition and response variability.
AB  - NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as
      xenoreceptors. Upon activation by various xenobiotics, including marketed drugs,
      they regulate the transcription level of major drug-metabolizing enzymes and
      transporters and facilitate the elimination of xenobiotics from the body. The
      modulation of the activity of these two xenoreceptors by various ligands is a
      major source of pharmacokinetic variability of environmental origin. NR1I2 and
      NR1I3 genetic polymorphisms can affect the pharmacokinetics and therapeutic
      response to many drugs, such as irinotecan, tacrolimus and atazanavir. This
      review provides an overview of NR1I2 and NR1I3 pharmacogenetic studies in various
      therapeutic fields (oncology, immunomodulation and infectiology) and discusses
      the implementation of NR1I2 and NR1I3 genetic polymorphism testing in the
      clinical routine.

PMID- 29199542
TI  - Medication use among pediatric patients with chronic musculoskeletal pain
      syndromes at initial pain clinic evaluation.
AB  - AIM: To characterize medication use by adolescents with chronic musculoskeletal
      pain syndromes before an initial multidisciplinary clinic visit. PATIENTS &
      METHODS: A cross-sectional sample of 120 adolescents and parents reported on
      standardized assessment measures, with medication use data extracted from the
      medical chart and categorized. RESULTS: On average, 3.2 medications were
      reported; 70% used more than one pain-specific medication including opioids
      (17%), nonopioids (31%), psychotropics/neuropathics (45%) and other medications
      (13%). Adolescents with complex regional pain syndrome consistently reported
      greatest use of opioid, psychotropic/neuropathic and other pain medications. A
      regression model explained 17% of the variance in pain medication use. Nonpain
      medication use and disability contributed unique variance - pain duration and
      intensity did not. CONCLUSION: Greater attention to factors contributing to
      prescriptive practices, medication use and long-term outcomes is warranted.

PMID- 29199544
TI  - The efficacy of a telemedicine-based weight loss program with video conference
      health coaching support.
AB  - Introduction Clinically significant weight loss is defined as a >=5% of initial
      body weight loss within a 6-month period. The purpose of this study was to assess
      body weight change from a 12-week telehealth-based weight loss program that
      integrated health coaching via video conferencing. Methods A total of 25 obese
      participants (12 males, 13 females) were recruited for this fully online 12-week
      weight loss program. Participants were randomly assigned to either an
      intervention group or control group ( n = 13 intervention, body mass index (BMI)
      = 34.7 +/- 4.5 kg/m2; n = 12 control, BMI = 34.4 +/- 4.43 kg/m2). All
      participants were given access to a secure platform for data tracking and video
      conferencing with the research team. The intervention group met with the medical
      doctor once per month and with a registered dietitian, weekly. Control
      participants met with the research team at baseline and at 12 weeks. Independent
      samples t-tests and Chi-square tests were used via SPSS version 24 with
      significance set to p < 0.05. Results There was a significant difference between
      the intervention and control groups for body weight loss (7.3 +/- 5.2 versus 1.2
      +/- 3.9 kg, respectively, p < 0.05) as well as for percent body weight loss (7.16
      +/- 4.4 versus 1.5 +/- 4.1%, respectively, p < 0.05). Clinically significant
      weight loss was achieved in 9 out of 13 (69.2%) in the intervention group versus
      1 out of 12 (8%) in the control group. Discussion Mobile phone-based health
      coaching may promote weight loss. Weekly video conferencing with education may be
      an applicable tool for inducing significant body weight loss in obese
      individuals.

PMID- 29199545
TI  - The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y
      mutation in H1N1 influenza virus.
AB  - Oseltamivir (Tamiflu) is the most accepted antiviral drug that targets the
      neuraminidase (NA) protein to inhibit the viral release from the host cell. Few
      H1N1 influenza strains with the H274Y mutation creates drug resistance to
      oseltamivir. In this study, we report that flavonoid cyanidin-3-sambubiocide
      (C3S) compound acts as a potential inhibitor against H274Y mutation. The drug
      resistance mechanism and inhibitory activity of C3S and oseltamivir against wild
      type (WT) and H274Y mutant-type (MT) have been studied and compared based on the
      results of molecular docking, molecular dynamics, and quantum chemical methods.
      Oseltamivir has been found less binding affinity with MT. C3S has more binding
      affinity with WT and MT proteins. From the dynamical study, the 150th loop of the
      MT protein has found more deformation than WT. A single H274Y mutation induces
      the conformational changes in the 150th loop which leads to produce more
      resistance to oseltamivir. The 150th cavity is more attractive target for C3S to
      stop the conformational changes in the MT, than 430th cavity of NA protein. The
      C3S is stabilized with MT by more number of hydrogen bonds than oseltamivir. The
      electrostatic interaction energy shows a stronger C3S binding with MT and this
      compound may be more effective against oseltamivir-resistant virus strains.

PMID- 29199546
TI  - Social networks, migration, and HIV testing among Latinos in a new immigrant
      destination: Insights from a qualitative study.
AB  - Latinos in the U.S. are disproportionately affected by HIV and are more likely
      than non-Latinos to present with a late diagnosis, which delays engagement in HIV
      care and treatment. Social networks may provide normative influence and social
      support for HIV testing, but a contextualised understanding of networks is needed
      in order to maximise these social resources. We conducted qualitative interviews
      with foreign-born Latino men and transgender women (n = 17) in a new immigrant
      destination to explore their social networks. Most participants described having
      smaller social networks after migrating. Networks included both local and
      transnational ties, but most participants had few close ties. Contextual factors
      including stigma and geographic dispersion limited the re-construction of
      networks with close ties after migration. HIV testing was not a common topic of
      discussion with social network ties. Efforts to improve early uptake of HIV
      testing among Latino immigrants may benefit from engaging with social networks,
      but such efforts need to address how the context in which networks operate
      enables access to testing.

PMID- 29199548
TI  - Abstracts of the Third National Poct Symposium, Antwerp, Belgium, March 17th,
      2017.

PMID- 29199547
TI  - From ships to robots: The social relations of sensing the world ocean.
AB  - The dominant practices of physical oceanography have recently shifted from being
      based on ship-based ocean sampling and sensing to being based on remote and
      robotic sensing using satellites, drifting floats and remotely operated and
      autonomous underwater vehicles. What are the implications of this change for the
      social relations of oceanographic science? This paper contributes to efforts to
      address this question, pursuing a situated view of ocean sensing technologies so
      as to contextualize and analyze new representations of the sea, and interactions
      between individual scientists, technologies and the ocean. By taking a broad view
      on oceanography through a 50-year shift from ship-based to remote and robotic
      sensing, I show the ways in which new technologies may provide an opportunity to
      fight what Oreskes has called 'ideologies of scientific heroism'. In particular,
      new sensing relations may emphasize the contributions of women and scientists
      from less well-funded institutions, as well as the ways in which oceanographic
      knowledge is always partial and dependent on interactions between nonhuman
      animals, technologies, and different humans. Thus, I argue that remote and
      robotic sensing technologies do not simply create more abstracted relations
      between scientists and the sea, but also may provide opportunities for more
      equitable scientific practice and refigured sensing relations.

PMID- 29199549
TI  - Characterization of moderately halotolerant selenate- and tellurite-reducing
      bacteria isolated from brackish areas in Osaka.
AB  - Moderately halotolerant selenate- and tellurite-reducing bacteria were
      characterized for wastewater treatment applications. A selenate-reducing strain
      9a was isolated from the biofilm of a leachate treatment plant at a sea-based
      waste disposal site. A tellurite-reducing strain Taa was isolated from an
      enrichment culture derived from brackish sediment. Both bacterial strains were
      Shewanella species. Strain 9a could anaerobically remove 45-70% of 1.0 mM
      selenate and selenite from water containing up to 3% NaCl within 4 days, while
      strain Taa could anaerobically and aerobically remove 70-90% of 0.4 mM tellurite
      from water containing up to 6% NaCl within 3 days. Globular particles of
      insoluble selenium were observed both outside and inside the cells of strain 9a.
      The insoluble tellurium formed by strain Taa was globular under microaerobic
      conditions but nanorod under aerobic conditions. These bacteria will yield a
      range of useful selenium and tellurium nanomaterials as well as wastewater
      treatment applications.

PMID- 29199550
TI  - Facilitating dual careers by improving resistance to chronic stress: effects of
      an intervention programme for elite student athletes.
AB  - The starting point of this contribution is the potential risk to health and
      performance from the combination of elite sporting careers with the pursuit of
      education. In European sport science and politics, structural measures to promote
      dual careers in elite sports have been discussed increasingly of late. In
      addition to organisational measures, there are calls for educational
      psychological intervention programmes supporting the successful management of
      dual careers at the individual level. This paper presents an appropriate
      intervention programme and its evaluation: stress-resistance training for elite
      athletes (SRT-EA). It comprises 10 units, each lasting 90 minutes. It is intended
      for athletes and aims to improve their resistance to chronic stress. The
      evaluation was carried out in a quasi-experimental design, with three points of
      measurement (baseline, immediately after, and three months after) and two non
      randomised groups: an intervention group (n = 128) and an untreated control group
      (n = 117). Participants were between 13 and 20 years of age (53.5% male) and
      represented various Olympic sports. Outcome variables were assessed with
      questionnaires. Significant short- and mid-term intervention effects were
      explored. The intervention increased stress-related knowledge, general self
      efficacy, and stress sensitivity. Chronic stress level, stress symptoms, and
      stress reactivity were reduced. In line with the intention of the intervention,
      the results showed short- and mid-term, small to medium-sized effects.
      Accordingly, separate measurements at the end of the intervention and three
      months later showed mostly positive subjective experiences. Thus, the results
      reinforce the hope that educational-psychological stress-management interventions
      can support dual careers.

PMID- 29199551
TI  - Royal Sun Culinary-Medicinal Mushroom, Agaricus brasiliensis (Agaricomycetes),
      Supplement in Training Capacity Improvement Parameters.
AB  - People seek a greater quality of life and healthy aging that culminates in
      improved self-esteem and vitality in the performance of daily activities; this is
      generating a growing number of people enrolled in gyms in search of quick
      results. However, this training can result in physical and metabolic damage.
      During physical exercise, under conditions of oxidative stress, changes take
      place that lead to the onset of fatigue. The Agaricus brasiliensis mushroom is
      native to Brazil and has therapeutic potential, with widely studied antioxidant
      and immunomodulatory capabilities. However, little is known about its potential
      benefits regarding muscular strength. Therefore, this study evaluated the
      possible effects of supplementation with this mushroom with respect to strength
      performance before and after a resistance training session. A blinded randomized
      trial was performed with male volunteers (n = 5) randomly divided into 2 groups
      (placebo and treatment with A. brasiliensis). Perceptions of muscle soreness and
      performance were assessed before and after high-intensity resistance training
      sessions. The study was executed over a 24-day period. Promising results were
      found related to intrasession rapid strength, most likely a result of antioxidant
      action and redox balance. The bioactive compounds in A. brasiliensis revealed the
      potential to improve conditions of muscle fatigue without altering other
      parameters. Thus, this mushroom has become a target of great expectations in the
      fields of fitness and athletics.

PMID- 29199552
TI  - In Vitro and In Vivo Antitumoral Activity of Exobiopolymers from the Royal Sun
      Culinary-Medicinal Mushroom Agaricus brasiliensis (Agaricomycetes).
AB  - We studied antitumor activity in vitro and in vivo and partial chemical
      characterization of exobiopolymers (EBPs) of Agaricus brasiliensis produced by
      submerged cultivation. The EBPs comprised 61.2% total sugar and 22.3% total
      protein, and the chromatographic profile mainly identified mannose (65.5%),
      galactose (17.5%), and glucose (13.1%). In vitro analysis revealed a dose with
      antitumor effectiveness, time-dependent treatment, and 46% inhibition of solid
      Walker 256 tumors in rats. Metabolic changes were significant in the spleens of
      the animals; this is possibly related to higher immune activity triggered by the
      presence of EBPs in the treated group. The increase of nitric oxide production by
      peritoneal macrophages from animals may be related to the tumor reduction
      observed, because nitric oxide acts as an important effector pathway in the
      defense of the organism.

PMID- 29199553
TI  - Apoptotic Effect of Taiwanofungus salmoneus (Agaricomycetes) Mycelia and Solid
      State Fermented Products on Cancer Cells.
AB  - Because of the high incidence of and high mortality rates associated with cancer,
      effective therapy for cancer is currently an imperative issue. Taiwanofungus
      salmoneus, a medicinal mushroom indigenous to Taiwan, has been demonstrated to
      exhibit various physiological activities and harmless effects. The bioactive
      compounds and anticancer abilities of T. salmoneus mycelia and fermented products
      were evaluated in this study. Total phenols, flavonoids, and ergothioneine were
      detected in mycelia and fermented products, and the amount of ergothioneine was
      evaluated in buckwheat (56.25-118.64 MUg/g extract) and oats (53.60-138.70 MUg/g
      extract) after fermentation. Results showed that T. salmoneus-fermented buckwheat
      and oats exhibited better apoptotic effects on Sk-Hep-1 and Caco-2 cells than
      sorafenib and celecoxib via receptor-linked apoptosis and mitochondria-mediated
      apoptosis. In addition, T. salmoneus-fermented buckwheat may have potential for
      replacing anticancer drugs or for consumption as a dietary supplement to retard
      cancer development.

PMID- 29199554
TI  - Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi
      Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA
      Reductase Activity.
AB  - Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits,
      including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory,
      anti-platelet aggregation, and antithrombotic effects. In this article, we
      describe our investigations of the in vitro antioxidant activity and in vitro
      antiatherosclerotic potential through inhibitory effects on low-density
      lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A
      (HMG-CoA) reductase catalytic activity using various fruiting body extracts
      partitioned with an organic solvent. Among 5 extracts/fractions tested, the
      semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity
      based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical
      scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant
      capacity, and lipid peroxidation assays. The EA fraction also showed the
      strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid
      reactive substances formation and HMG-CoA reductase activity. Chemical analysis
      conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3
      flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone
      derivative), some of which play pivotal roles in arresting the physiopathogenesis
      of atherosclerosis, thereby attenuating the risk of cardiovascular events
      occurring.

PMID- 29199555
TI  - Immune-Stimulating Effects of Mycoleptodonoides aitchisonii (Agaricomycetes)
      Water Extract via TNF-alpha and IFN-gamma.
AB  - Mycoleptodonoides aitchisonii has been used as culinary material in East Asia. We
      previously reported the antiasthmatic effect of M. aitchisonii; in this study we
      evaluated the mushroom's immune-stimulating effects. To analyze these effects, we
      conducted an in vitro study with splenocytes and an in vivo study with the
      Porsolt enforced swim test. In the in vitro study, the cell proliferation effect
      of the M. aitchisonii water extract (WT) was measured and the in vivo study
      depended on the dose of M. aitchisonii WT and the effect on swimming duration;
      several immune reaction-related factors were assessed, such as white blood cell
      count, differential cell count, the ratio of thymus or spleen weight to body
      weight, and concentrations of some cytokines in serum. Almost all measured
      factors that are related to immune stimulation were dose-dependently increased,
      such as the number of splenocytes and monocytes, the swimming duration, the
      relative weight of the thymus, and the expression of tumor necrosis factor (TNF)
      alpha and interferon (IFN)-gamma. Based on the results, we conclude that M.
      aitchisonii WT has an immune-stimulating effect via TNF-alpha and IFN-gamma, and
      that M. aitchisonii WT is an immune-stimulating agent and can be produced as a
      functional food.

PMID- 29199556
TI  - Brown Mycelial Mat as an Essential Morphological Structure of the Shiitake
      Medicinal Mushroom Lentinus edodes (Agaricomycetes).
AB  - We show here, to our knowledge for the first time, that the brown mycelial mat of
      the xylotrophic shiitake medicinal mushroom, Lentinus edodes, not only performs a
      protective function owing to significant changes in the ultrastructure
      (thickening of the cell wall, increased density, and pigmentation of the fungal
      hyphae) but also is a metabolically active stage in the development of the
      mushroom. The cells of this morphological structure exhibit repeated activation
      of expression of the genes lcc4, tir, exp1, chi, and exg1, coding for laccase,
      tyrosinase, a specific transcription factor, chitinase, and glucanase, which are
      required for fungal growth and morphogenesis. This study revealed the maximum
      activity of functionally important proteins with phenol oxidase and lectin
      activities, and the emergence of additional laccases, tyrosinases, and lectins,
      which are typical of only this stage of morphogenesis and have a regulatory
      function in the development and formation of fruiting bodies.

PMID- 29199557
TI  - Nutritional Requirements for Mycelial Growth of Milk-White Toothed Mushroom,
      Irpex lacteus (Agaricomycetes), in Submerged Culture.
AB  - Irpex lacteus, a medicinal fungus, is used in traditional Chinese medicine to
      treat chronic glomerulonephritis. In this work, a strain of I. lacteus was
      isolated from the fruiting body of a wild specimen and identified by ITS-5.8S
      ribosomal DNA sequencing analysis. Then the nutritional requirements and culture
      conditions for mycelial growth of I. lacteus in semisynthetic liquid media were
      investigated using the one-factor-at-a-time and orthogonal matrix methods.
      Optimum growth occurred at 30 degrees C and 35 degrees C. I. lacteus mycelia grew
      well at pH values between 3 and 9, suggesting that this strain is not sensitive
      to pH. The nutritional components, including 9 carbohydrates, 9 nitrogen
      compounds, 11 vitamins, and 10 mineral elements, were studied for their effects
      on mycelial growth in submerged cultures of I. lacteus. Among these variables,
      soluble starch, peptone, yeast extract, and calcium chloride were identified as
      required for optimum mycelial growth. The concentrations of each component were
      optimized using an orthogonal design, and the effects of medium composition on
      mycelial growth were found in the order soluble starch > yeast extract > peptone
      > calcium chloride. The optimal concentrations of these components for mycelial
      growth were determined to be 60 g/L soluble starch, 35 g/L peptone, 15 g/L yeast
      extract, and 0.6 g/L calcium chloride. Under the optimum medium and culture
      conditions, the maximum biomass reached 13.73 g/L after 3 days in submerged
      culture, a value over twice that reached using the basal medium. These results
      provide a basis for further physiological study and industrial fermentation of I.
      lacteus.

PMID- 29199558
TI  - Identification and Evaluation of Bioactivity of Compounds from the Mushroom
      Pleurotus nebrodensis (Agaricomycetes) against Breast Cancer.
AB  - Breast cancer affects millions of women annually worldwide and is the leading
      cause of cancer death in women. Various bioactive phytochemicals based on natural
      products are considered to be an important source of chemopreventive agents. In
      this study we report-to our knowledge for the first time-9 phytochemicals
      isolated by nuclear magnetic resonance spectroscopy and mass spectrometry from
      the acetic ether extract of Pleurotus nebrodensis and identified as (1)
      ergosterol, (2) uracil, (3) ergosterol-3-O-beta-D-glucopyranoside, (4)
      cerevisterol, (5) cerebroside B, (6) 5'-methylthioadenosine, (7) adenosine, (8)
      hypoxanthine, and (9) uridine. Their bioactivities were screened with an MTT
      assay using breast cancer MCF-7 cells in vitro. As a result, about half of the
      isolated compounds demonstrated moderate or strong inhibitory activity in a
      concentration-dependent manner. Among them, compound 1 (ergosterol) exhibited
      superior activity and the lowest half-maximal inhibitory concentration (112.65
      MUmol/L). Further mechanistic study elucidated that compound 1 led to significant
      S-phase cell cycle arrest and induced apoptosis in MCF-7 cells. Our study shows
      the mycochemical composition of the P. nebrodensis mushroom and provides guidance
      for use of compound 1 as a promising lead in cancer therapy.

PMID- 29199559
TI  - Growth-Inhibitory and Immunomodulatory Activities of Wild Mushrooms from North
      Central British Columbia (Canada).
AB  - Wild mushrooms, especially from North America, have not been systematically
      explored for their medicinal properties. Here we report screening for the growth
      inhibitory and immunomodulatory activities of 12 species collected from multiple
      locations in north-central British Columbia, Canada. Mushrooms were characterized
      using morphology and DNA sequencing, followed by chemical extraction into 4
      fractions using 80% ethanol, 50% methanol, water, and 5% sodium hydroxide. Growth
      inhibitory, immunostimulatory, and anti-inflammatory activities of 5 mushrooms
      (Leucocybe connata, Trichaptum abietinum, Hydnellum sp., Gyromitra esculenta, and
      Hericium coralloides) are reported here, to our knowledge for the first time.
      Growth-inhibitory effects were assessed using the cytotoxic MTT assay.
      Immunostimulatory activity was assessed by tumor necrosis factor-alpha production
      in Raw 264.7 macrophages, whereas anti-inflammatory activity was assessed based
      on the inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha
      production. The ethanol and aqueous extracts of Hydnellum sp. were potent growth
      inhibitors, with a half-maximal inhibitory concentration of 0.6 mg/mL. All 5
      fungi displayed strong immunostimulatory activity, whereas only L. connata and T.
      abietinum showed strong anti-inflammatory activity. For the 7 other fungi
      investigated, which included well-known medicinal species such as Inonotus
      obliquus, Phellinus igniarius, and Ganoderma applanatum, the remarkable
      similarities in the biological activities reported here, and by others for
      specimens collected elsewhere, suggest that mushrooms can produce similar
      metabolites regardless of their habitat or ecosystem. This is to our knowledge
      the first study to explore wild mushrooms from British Columbia for biological
      activities that are relevant to cancer, and the results provide an initial
      framework for the selection of mushroom species with the potential for discovery
      of novel anticancer compounds.

PMID- 29199560
TI  - Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Modulates
      Purinoceptor-Coupled Calcium Signaling and Murine Nociceptive Behavior.
AB  - Hericium erinaceus is well known for the neurotrophic effect it confers by
      promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of
      H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced
      calcium signaling in neuronal PC12 cells. ATP, known primarily as a
      neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to
      generate the cellular calcium signaling and secretion that mediate P2R
      physiological manifestations, including pain. Chronic pain reduces quality of
      life. However, constant analgesic administration can cause liver and kidney
      injury, as well as loss of the analgesic effect because of desensitization. In
      this study we investigated the analgesic potential of H. erinaceus through
      measurements of ATP-induced Ca2+ signaling in cell lines and observation of pain
      behaviors in mice. In P2R-coupled Ca2+ signaling measurements, extracts of H.
      erinaceus mycelia (HEEs) blocked ATP-induced Ca2+ signaling in both rat PC12
      cells and human HOS cells. HEEs completely blocked ATP-induced Ca2+ signaling in
      human HOS cells, suggesting that this effect of HEEs is exerted through the P2R
      subtypes present in HOS cells, which include the P2X4, P2X7, P2Y2, and P2Y4
      subtypes. In observations of animal behavior during pain, HEEs significantly
      reduced heat-induced pain, including postponing both the tail-flick response to
      heat stimulation and the paw-lifting response to a hot plate. This study
      demonstrates novel characteristics of H. erinaceus in reducing nociceptive
      behavior and blocking the functional activity of P2R. Further studies are
      required to verify this linkage and its molecular mechanisms.

PMID- 29199561
TI  - Antifungal, Antioxidative, and Genoprotective Properties of Extracts from the
      Blushing Bracket Mushroom, Daedaleopsis confragosa (Agaricomycetes).
AB  - This study aimed to evaluate the antifungal, antioxidative, and genoprotective
      potentials of various extracts of Daedaleopsis confragosa fruiting bodies and
      mycelia. The extracts exhibited weak fungistatic and an absence of any fungicidal
      activities against 7 important animal and human pathogens. Although mycelial
      extracts, especially the hot water extract, were more effective antifungal agents
      than basidiocarp extracts, they were significantly weaker than the commercial
      antimycotic ketoconazole. The tested extracts reduced DPPH radicals to various
      extents, depending on the material used for extraction and the solvent. The
      mycelial hot water extract was the best DPPH radical scavenger (half-maximal
      effective concentration, 3.42 mg mL-1), whereas the 96' ethanol extract of
      basidiocarps was the weakest one (half-maximal effective concentration, 5.36 mg
      mL-1). Phenols were the main carriers of activity, and their proportions in the
      tested extract mainly depended on the type and concentration of the solvent; the
      effect of the material used for extraction was negligible. The largest amount of
      phenols was detected in the 70% ethanol extract of basidiocarps (126.40 MUg
      gallic acid equivalents mg-1) and the lowest in the basidiocarp methanol extract
      (19.93 MUg gallic acid equivalents mg-1). Aqueous extracts of basidiocarp and
      mycelial extracts were not genotoxic agents but exhibited significant protective
      activity against hydrogen peroxide-induced DNA damage during use in leukocytes'
      pre- and post-treatments.

PMID- 29199562
TI  - Immunomodulatory Effects of Extracellular beta-Glucan Isolated from the King
      Oyster Mushroom Pleurotus eryngii (Agaricomycetes) and Its Sulfated Form on
      Signaling Molecules Involved in Innate Immunity.
AB  - The aim of this study was to determine, using murine RAW 264.7 macrophages, the
      immunomodulatory effect of extracellular beta-glucan isolated from Pleurotus
      eryngii (PEBG) and its sulfated derivative (PEBG-S) on signaling molecules
      implicated in host innate immunity. beta-Glucan was extracted and purified from
      the mycelial culture using optimal medium concentrations. It was then chemically
      converted to its sulfated form. Monosaccharide composition of beta-glucan was
      characterized with p-aminobenzoic acid ethyl ester-derivatized sugars through
      highperformance liquid chromatography analysis. Fourier transform infrared
      structural analysis showed an S=O bond at 1250 cm-1 and C-S-O binding at 815 cm-1
      in PEBG-S. 13C nuclear magnetic resonance analysis showed 1,3-linked alpha-D
      mannopyranosyl and 1,3-beta-D-glucopyranosyl in PEBG-S. A concentration-dependent
      increase of nitric oxide production was noticed in RAW 264.7 cells treated with
      PEBG-S or PEBG; those treated with PEBG-S showed less cytotoxicity than those
      treated with PEBG. Cellular levels of tumor necrosis factor-alpha, interleukin
      1beta, and interleukin-6 were increased by PEBG and PEBG-S treatment, suggesting
      that they have immunomodulatory activity. Real-time polymerase chain reaction
      array revealed that the expression levels of nuclear factor-kappaB and Toll-like
      receptor signaling genes in cells were upregulated by PEBG and PEBG-S. Moreover,
      the expression of the beta-glucan receptor dectin-2 was significantly upregulated
      by PEBG and PEBG-S treatment, reflecting immune activation through the dectin-2
      Syk-(CARD9/Bcl-10/MALT1) pathway. Our results suggest that PEBG-S could be used
      as an effective adjuvant or immune enhancer that can be sustainably produced by
      recycling the by-product of mycelial culture.

PMID- 29199563
TI  - Structural Characteristics of the Novel Polysaccharide FVPA1 from Winter Culinary
      Medicinal Mushroom, Flammulina velutipes (Agaricomycetes), Capable of Enhancing
      Natural Killer Cell Activity against K562 Tumor Cells.
AB  - FVPA1, a novel polysaccharide, has been isolated from fruiting bodies of the
      culinary-medicinal mushroom Flammulina velutipes, a historically popular, widely
      cultivated and consumed functional food with an attractive taste, beneficial
      nutraceutical properties such as antitumor and immunomodulatory effects, and a
      number of essential biological activities. The average molecular weight was
      estimated to be ~1.8 * 104 Da based on high-performance size exclusion
      chromatography. Sugar analyses, methylation analyses, and 1H, 13C, and 2
      dimensional nuclear magnetic resonance spectroscopy revealed the following
      structure of the repeating units of the FVPA1 polysaccharide Identification of
      this structure would conceivably lead to better understanding of the
      nutraceutical functions of this very important edible fungus. Bioactivity tests
      in vitro indicated that FVPA1 could significantly enhance natural killer cell
      activity against K562 tumor cells.

PMID- 29199564
TI  - Effect of Pulsed Light Irradiation on Bioactive, Nonvolatile Components and
      Antioxidant Properties of Caterpillar Medicinal Mushroom Cordyceps militaris
      (Ascomycetes).
AB  - The caterpillar medicinal mushroom Cordyceps militaris contains many bioactive
      components, such as adenosine, cordycepin, and polysaccharides. In this study, C.
      militaris was exposed to 0, 3, 6, or 9 pulses of light irradiation to estimate
      changes in vitamin D2, bioactive compounds, nonvolatile taste components, and
      antioxidant properties. In addition, we compared the components and properties of
      C. militaris mycelia and solid waste medium that had been treated with pulsed
      light (PL) irradiation. Overall, PL irradiation of C. militaris increased the
      vitamin D2 content and increased the total amino acid levels 9-48%; the
      antioxidant properties of the mycelia treated with 0 pulses and of the solid
      waste medium treated with 3 pulses all exhibited lower half-maximal effective
      concentrations. Therefore, PL irradiation affected the amounts of bioactive
      compounds, but the irradiated samples still contained intense umami taste and a
      sufficient amount of antioxidant components.

PMID- 29199565
TI  - Cytotoxic Activities of Fractions of the Willow Bracket Medicinal Mushroom,
      Phellinus igniarius (Agaricomycetes), and the Induction of Cell Cycle Arrest and
      Apoptosis in MGC-803 Cells.
AB  - Phellinus igniarius, a perennial medicinal mushroom, has been used in China and
      other countries of East Asia for the treatment of various diseases, including
      cancer. The purpose of this study is to evaluate the cytotoxic activities of
      different fractions of an ethanol extract from Ph. igniarius and to elucidate a
      possible antitumor mechanism. An ethanol extract of Ph. igniarius was partitioned
      into a petroleum ether fraction, an ethyl acetate fraction (EAF), an n-butanol
      fraction, and a water-soluble fraction. The cytotoxic activity of all the
      fractions was initially screened in a brine shrimp lethality test, then evaluated
      by the Cell Counting Kit-8 assay against 5 human tumor cell lines: MGC-803, BEL
      7402, HeLa, MCF-7, and HCT-116. The cell cycle distribution induced by EAF on MGC
      803 cells was analyzed by flow cytometry with propidium iodide staining, and
      apoptosis was determined using flow cytometry with Annexin V/propidium iodide
      staining. The results of the brine shrimp lethality test and the Cell Counting
      Kit-8 assay showed that EAF was the most active fraction, displaying strong
      inhibitory activity against the MGC-803, BEL-7402, and MCF-7 cancer cell lines.
      Flow cytometry analysis indicated that EAF could induce S-phase cell cycle arrest
      in MGC-803 cells and cause apoptosis in a concentration-dependent manner. This
      study demonstrated that EAF, as the most active fraction of Ph. igniarius,
      exerted antitumor activity by inducing MGC-803 cell apoptosis via S-phase cell
      cycle arrest.

PMID- 29199566
TI  - Clinical Effects of a Commercial Supplement of Ophiocordyceps sinensis and
      Ganoderma lucidum on Cognitive Function of Healthy Young Volunteers.
AB  - Ophiocordyceps sinensis (= Cordyceps sinensis) and Ganoderma lucidum are
      medicinal mushrooms used in traditional Chinese medicine. The effects of O.
      sinensis and G. lucidum on cognitive function have been evaluated through the use
      of animal models and in vitro studies, which indicated beneficial effects. The
      purpose of this study was to evaluate the effects of treatment with a
      commercially available supplement of O. sinensis and G. lucidum on cognitive
      function in young, healthy human participants. Physical education students (n =
      96 [53 men, 43 women]; mean +/- standard deviation age, 26.3 +/- 3.21 years) were
      randomly divided into 3 treatment groups: highdose supplement (HD) group, low
      dose supplement (LD) group, and a placebo (PL) group. Each group received the
      treatment, administered by a technician blinded to supplements/placebo, for 30
      days. Participants were evaluated for various cognitive functions before and
      immediately after treatment. Evaluation of cognitive function domains-global
      cognitive score, memory, executive function, attention, information processing
      speed, visuospatial ability, verbal function, and motor skills-showed no
      significant differences between groups. These results indicate that a combination
      of O. sinensis and G. lucidum supplements for 30 days did not enhance cognitive
      function domains in young healthy participants.

PMID- 29199567
TI  - Isolation and Characterization of Lectin from the Artist's Conk Medicinal
      Mushroom, Ganoderma applanatum (Agaricomycetes), and Evaluation of Its
      Antiproliferative Activity in HT-29 Colon Cancer Cells.
AB  - The growth and lectin production of Ganoderma applanatum, a white rot fungus, was
      optimized in broth cultures. The fungus was found to have a higher growth rate
      and higher lectin activity when grown in a medium adjusted to pH 6.5 at 26
      degrees C under stationary conditions. Expression of lectin activity started in 5
      day-old mycelial culture; maximum activity was expressed after the 15th day of
      incubation. Among the various carbon and nitrogen sources tested, the carbon
      source sucrose and the nitrogen source yeast extract support maximum growth and
      lectin production. Lectin from G. applanatum was purified by ammonium sulfate
      precipitation and ion exchange chromatography. The purified fraction revealed a
      single band with a molecular weight of 35.0 kDa. Moreover, carbohydrates such as
      mannitol, glucose, sucrose, maltose, mannose, galactose, sorbose, and fructose
      were found to inhibit the hemagglutinating activity of the lectin. The purified
      lectins from G. applanatum contain cytotoxic and proapoptotic activities against
      HT-29 colon adenocarcinoma cells.

PMID- 29199568
TI  - Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes),
      Inhibits Candida Biofilms: A Metabolomic Approach.
AB  - This article presents a comparative gas chromatography (GC)-mass spectrometry
      (MS)-based metabolomic analysis of mycelia and fruiting bodies of the medicinal
      mushroom Ganoderma lucidum. Three aqueous extracts-mycelia, fruiting bodies, and
      a mixture of them-and their sequential fractions (methanolic and ethyl acetate),
      prepared using an accelerated solvent extractor, were characterized by GC-MS to
      determine volatile organic compounds and by high-performance thin-layer
      chromatography to quantify ascorbic acid, a potent antioxidant. In addition,
      these extracts and fractions were assessed against Candida albicans and C.
      glabrata biofilms via the XTT reduction assay, and their antioxidant potential
      was evaluated. Application of chemometrics (hierarchical cluster analysis and
      principal component analysis) to GC data revealed variability in volatile organic
      compound profiles among G. lucidum extracts and fractions. The mycelial aqueous
      extract demonstrated higher anti-Candida activity and ascorbic acid content among
      all the extracts and fractions. Thus, this study illustrates the preventive
      effect of G. lucidum against C. albicans and C. glabrata biofilms along with its
      nutritional value.

PMID- 29199569
TI  - Enzymatic System of Antioxidant Protection of Erythrocytes in Diabetic Rats
      Treated with Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum
      (Agaricomycetes).
AB  - Excessive glucose concentrations in blood and cells promote the intensification
      of auto-oxidation. This is one of the mechanisms through which free radicals form
      in hyperglycemia. As a result of hyperglycemia, oxidative stress develops and
      lipid peroxidation (LPO) is enhanced. Erythrocytes are particularly susceptible
      to reactive oxygen species and LPO, which can violate cell functions. This
      article describes the analysis of the influence of mycelia from the medicinal
      mushrooms Agaricus brasiliensis and Ganoderma lucidum on the enzymatic link of
      the antioxidant system in rat erythrocytes under streptozotocin-induced diabetes
      mellitus. Oxidative stress was strengthened in red blood cells of diabetic rats,
      as evidenced by decreased activity of antioxidant enzymes such as superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase, and by
      increased amounts of thiobarbituric acid-positive products, which are markers of
      LPO. Administration of A. brasiliensis and G. lucidum submerged cultivated
      mycelial powder to animals with streptozotocin-induced diabetes restored
      superoxide dismutase, catalase, and glutathione peroxidase activity and reduced
      the amounts of thiobarbituric acid-positive products to control values, but did
      not affect the activity of glutathione reductase.

PMID- 29199570
TI  - Selective Cytotoxic Activity of Se-Methyl-Seleno-L-Cysteine- and Se
      Polysaccharide-Containing Extracts from Shiitake Medicinal Mushroom, Lentinus
      edodes (Agaricomycetes).
AB  - Numerous formulations derived from the shiitake medicinal mushroom, Lentinus
      edodes, demonstrate anticancer activities. We hypothesized that isolates from
      selenium (Se)-enriched mycelia of L. edodes would possess stronger cancer
      preventive properties than current preparations. The aim of this study was to
      investigate whether the presence of Se-methyl-seleno-L-cysteine in mycelial
      extracts of L. edodes affects their cytotoxic activity (makes them stronger) or
      whether they are as effective as Se-containing polysaccharides. Extracts were
      prepared from Se-containing mycelia under various conditions and assayed for
      cytotoxic activity in cancer (PC3 and HeLa) and normal (HMEC-1) cell lines. The
      chemical composition of the extracts was examined; specifically, the amounts of
      potentially cytotoxic Se compounds (methylselenocysteine, selenomethionine, and
      Se-containing polysaccharides) were measured. The relationship between extract
      composition and biological activity was characterized. Mycelial cultures were
      cultivated in a 10-L bioreactor in medium enriched with sodium selenite. Mycelial
      extracts were prepared either at 100 degrees C or at 4 degrees C in acidic
      solution. Total Se content was determined using the atomic absorption
      spectrometry method, and methylselenocysteine and selenomethionine contents were
      measured using reverse-phase high-performance liquid chromatography. Protein,
      carbohydrate, and polyphenolic contents were determined with spectrophotometric
      methods, and Se-containing polysaccharides were measured with the use of
      precipitation. Anticancer activity of mycelial extracts was examined using the
      MTT cell viability assay. Extracts containing Se-methyl-seleno-L-cysteine or Se
      polysaccharides prepared at 4 degrees C and 100 degrees C, respectively, display
      moderate, time-dependent, specific cytotoxic activity in HeLa and PC3 cell lines.
      The effect in HeLa cells is more pronounced in the extract prepared at 4 degrees
      C than at 100 degrees C. The effect is almost equal for the PC3 cell line.
      However, both extracts have no effect or only slightly stimulate normal (HMEC-1)
      cell viability. The selective cytotoxic activity of L. edodes extracts in cancer
      (PC3 and HeLa) cells is due to the presence of both Se-methyl-seleno-L-cysteine
      and selenated polysaccharides, perhaps in combination with other active
      ingredients.

PMID- 29199571
TI  - Genotoxicity and Single-Treatment Toxicity Evaluation of Mycoleptodonoides
      aitchisonii (Agaricomycetes) Water Extract.
AB  - Mushrooms have long been used worldwide for culinary and medicinal purposes
      because of their various nutrients and active constituents. The safety of
      mushrooms as a culinary ingredient requires validation. Although
      Mycoleptodonoides aitchisonii has long been used for culinary purposes in East
      Asia, it has not been authorized by a regulatory agency. In this study we
      conducted genotoxicity and single-treatment toxicity tests according to the
      guidelines of the Organisation for Economic Co-operation and Development. We
      performed genotoxicity tests (bacterial reverse mutation study, chromosome
      aberration test, and micronucleus test), single-treatment toxicity tests, and in
      vivo mammalian alkaline comet assay of M. aitchisonii water extract (WT). A
      single treatment with 5000 mg/kg M. aitchisonii WT showed no toxicity. M.
      aitchisonii WT induced bacterial reverse mutation and chromosome aberration but
      showed a negative result in the micronucleus test. Thus, an in vivo mammalian
      alkaline comet assay was performed; however, no genotoxicity was detected.
      Treatment with <5000 mg/kg M. aitchisonii WT is nontoxic and can be used for
      culinary purposes.

PMID- 29199572
TI  - Acute and Subchronic Toxicity of Dusky-Skinned Mushroom, Amauroderma rude
      (Agaricomycetes).
AB  - Our earlier work indicated that Amauroderma rude seems to have an effect on
      immunoregulation and tumor inhibition. However, its toxicity is not yet clear.
      The aim of this work is to demonstrate the acute and subchronic toxicity of A.
      rude in order to provide a scientific basis for its possible use as a food. The
      acute toxicity study (involving mice) showed that the median lethal dose of the
      A. rude extract was >15,000 mg/kg. In the repeated-dose 90-day oral toxicity
      study (involving rats), the administration of A. rude extract at 0.1 (AR0.1), 0.2
      (AR0.2), and 0.4 g (AR0.4) per rat produced no significant difference in food or
      water consumption or changes in body weight, hematological parameters,
      biochemical parameters, relative organ weights, organ coefficients, or
      histopathology compared with the control group. Analyses of these results with
      data from monitoring the appearance, behavior, and health of the animals indicate
      that the oral administration of A. rude extract daily for 90 days does not cause
      subchronic toxicity.

PMID- 29199573
TI  - Effects of Culture Conditions on Antimicrobial Activity of Ganoderma resinaceum
      (Agaricomycetes) Extracts.
AB  - Among many sources of natural bioactive substances, mushrooms constitute a huge
      and mostly unexplored group. Biologically active secondary metabolites of
      Ganoderma, a group of wood-degrading mushrooms, have recently been reviewed. Our
      previous study revealed the antimicrobial activity of extracts from G. resinaceum
      grown in submerged culture against phytopathogens. Different factors can
      influence the production of secondary metabolites, including nutritional factors.
      In this study we evaluated the influence of different culture conditions on the
      antimicrobial activity of extracts from liquid cultures of G. resinaceum, through
      use of a factorial design. Minimum inhibitory concentrations for extracts
      produced under different culture conditions were determined against
      Staphylococcus aureus and Xanthomonas vesicatoria. Based on the results of these
      assays, larger-scale cultures in malt extract broth supplemented with 20 g/L
      glucose and a 15-day incubation time should be performed in order to isolate from
      G. resinaceum antibiotic compound(s) that are potentially useful against S.
      aureus. In addition, pH 5 should be considered for the production of
      antimicrobial metabolites against X. vesicatoria from supernatant broths or
      extracts from G. resinaceum.

PMID- 29199574
TI  - Immunoreactivity of the Cold Water Extract of Royal Sun Culinary-Medicinal
      Mushroom, Agaricus brasiliensis Strain KA21 (Agaricomycetes), Assessed by
      Immunoglobulin Preparations for Intravenous Injection.
AB  - The royal sun medicinal mushroom, Agaricus brasiliensis, is a health food
      material that helps to improve quality of life. A. brasiliensis has long been
      used as a tea by extraction with cold and hot water. Our group has been
      investigating the immunopharmacological activities of the A. brasiliensis KA21
      strain, which is cultivated outdoors. We prepared cold water (AgCWE) and hot
      water (AgHWE) extracts of this strain. AgCWE contained a larger proportion of
      proteins, including enzymes, and showed a brownish color during the extraction
      process. By contrast, chemical and immunochemical analyses revealed that AgHWE
      contained large amounts of beta-1,3-/1,6-glucans. In an attempt to elucidate the
      immunochemical characteristics of AgCWE, reactivities to immunoglobulin (Ig)
      preparations for intravenous injection were analyzed and compared with standard
      materials. To characterize brownish high-molecular weight components, standard
      phenol compounds such as caffeic acid (CA), trans-ferulic acid (FA), and coumaric
      acid (CouA) were polymerized to brownish polymerized polyphenols (PPPs) (i.e.,
      polymerized CA, polymerized FA, and polymerized CouA) by laccase or peroxidase.
      The results obtained revealed that intravenous Ig reacted with all PPPs and PPPs
      cross-reacted with AgCWE and AgHWE. The isotype of the anti-PPP antibody was
      found to be IgG1, in contrast to that of the beta-glucan antibody, which was
      mainly IgG2. These results strongly suggest that A. brasiliensis extracts contain
      immunoreactive components against various classes of Igs.

PMID- 29199575
TI  - Validation of Structural Equation Modeling Methods for Functional MRI Data
      Acquired in the Human Brainstem and Spinal Cord.
AB  - Structural equation modeling (SEM) provides a means of investigating
      relationships between blood oxygenation level-dependent (BOLD) signal changes in
      functional MRI data across neuroanatomical regions. The objectives of this study
      were to demonstrate adapted SEM methods for the brainstem and spinal cord,
      validate statistical methods and appropriate statistical thresholds, and test the
      methods with existing data. SEM methods were applied using an anatomical model of
      regions of the thalamus, brainstem, and spinal cord that are involved with pain
      processing. Statistical distributions (Z-scores), significance thresholds, and
      corrections for multiple comparisons were determined from repeated simulations
      using "null" data sets. SEM analyses were then applied to data from prior studies
      involving noxious stimulation in healthy participants. Z-score distributions were
      observed to vary with the number of source regions modeled, the number of time
      points (volumes) included in the analysis, and the time span (epoch) used for
      dynamic analyses. Appropriate choices of statistical thresholds and corrections
      for multiple comparisons were demonstrated. The results reveal consistent network
      features across/within studies, as well as dependences on study conditions. They
      show the effectiveness of a SEM method for functional MRI data from the brainstem
      and spinal cord.

PMID- 29199576
TI  - A Review of Point-Wise Motion Tracking Algorithms for Fetal Magnetic Resonance
      Imaging.
AB  - We review recent feature-based tracking algorithms as applied to fetal magnetic
      resonance imaging (MRI). Motion in fetal MRI is an active and challenging area of
      research, but the challenge can be mitigated by strategies related to patient
      setup, acquisition, reconstruction, and image processing. We focus on fetal
      motion correction through methods based on tracking algorithms for registration
      of slices with similar anatomy in multiple volumes. We describe five motion
      detection algorithms based on corner detection and region-based methods through
      pseudocodes, illustrating the results of their application to fetal MRI. We
      compare the performance of these methods on the basis of error in registration
      and minimum number of feature points required for registration. Harris, a corner
      detection method, provides similar error when compared to the other methods and
      has the lowest number of feature points required at that error level. We do not
      discuss group-wise methods here. Finally, we attempt to communicate the
      application of available feature extraction methods to fetal MRI.

PMID- 29199577
TI  - A Kinematic Approach to Understanding Performance in Upper-Extremity Function
      during a Goal-Directed Man-Machine Interface Task in a Submariner Environment.
AB  - In December of 2014, the United States Congress funded a fundamental shift in the
      recruiting policy of the US Navy Submarine Force to include the integration of
      women. As a result, design modifications became necessary, especially those that
      facilitate integration without inflating costs. Current cost levels associated
      with new submarine design(s) are maintained through the use of legacy components
      and systems. Additionally, many of the systems aboard are computer controlled,
      necessitating man-machine interfaces. As common practice, military activities
      that involve man-machine interfaces have always focused on the dexterity of the
      hands, often neglecting the role of movement in the task; therefore, there is a
      need to understand upper-extremity kinematics issues associated with man-machine
      interfaces. Joint kinematics of the right upper extremity of 10 subjects was
      measured using an optoelectronic motion capture system. Center of gravity
      displacements were measured using a force plate during touchscreen movement tasks
      paced by six different movement frequencies from a metronome (0, 1.0, 1.3, 1.7,
      2.0, and 2.7 Hz). Results showed no significant difference in touch accuracy,
      task completion time, shoulder and elbow angular displacements, and shoulder and
      elbow flexion/extension velocity; however, a significant difference (0.002; p <=
      0.05) in shoulder adduction/abduction velocity was observed. In arranging systems
      and components in submarine and surface vessel environments, consideration in not
      only providing a means of adjustability (e.g., height, proximity, and
      orientation) but in the dimensions of the systems and components themselves must
      also be considered based on the required operation.

PMID- 29199578
TI  - Energy Storage and Return Prostheses: A Review of Mechanical Models.
AB  - Conventional lower-limb mechanical models were originally developed for gait
      analysis of ablebodied Conventional lower-limb mechanical models were originally
      developed for gait analysis of ablebodied subjects and therefore potentially
      misrepresent prosthetic foot behavior when applied to modern energy storage and
      return (ESAR) prostheses. This review investigates the limitations of current
      models of prosthetic foot dynamics and kinematics. The Scopus online database was
      used to identify 236 articles on prosthetic foot behavior during either
      experiments or simulations, categorized into three main types of models: 74% (n =
      175) of studies featured a rigid-link model, 17% (n = 39) a lumped-parameter
      model and 10% (n = 23) finite element (FE) analysis. Notably, 64% (n = 152) of
      the studies used a conventional two-link segment model, yet only 8% (n = 20)
      featured the rigid, articulating prosthesis that satisfies this model's
      underlying rigid-body mechanics assumptions. Conversely, the available
      preliminary studies on multi-link segment, lumped-parameter and FE models present
      viable and more mechanically relevant alternatives to conventional techniques,
      particularly for ESAR prostheses. Expanding these alternative models to include
      inertial behavior, multiple-degrees of freedom and standardization of boundary
      conditions will lead towards both accurate and standardized prosthetic foot
      analysis.

PMID- 29199579
TI  - Review of the Dielectric Properties of Animal and Human Tumors Determined from In
      Vivo Measurements.
AB  - In this article, we combine a review of the wide range of tissue dielectric
      studies and applications (e.g., safety, imaging, therapy) being pursued by the
      bioelectromagnetics community with a description of one specific application of
      dielectric measurements (in vivo tumor classification). The tumor measurements
      were acquired over a frequency range of 0.01-4.0 GHz using a technique based on
      the impedance change recorded by a short antenna when placed near or in a lossy
      dielectric. Substantial differences (up to 300%) were found between the
      dielectric properties of tumors (mammary adenocarcinoma, melanoma, lung
      carcinoma, glioblastoma and ependymoblastoma) and normal host tissues. Such
      differences reflect the known heterogeneity of abnormal cell growth in cancer. In
      addition, in vivo human measurements of breast carcinoma, normal skin and breast
      tissue indicate that a maximum differential power absorption (30% higher in
      tumor) occurs between 1.0 and 2.0 GHz. This information, when combined with tumor
      size, geometry, and anatomical location, enable the design and development of
      effective systems for the detection of tumors and for electromagnetically induced
      differential hyperthermia treatment. Finally, we also discuss these results in
      the context of other impedance and dielectric approaches used to characterize
      normal and neoplastic cells and tissues.

PMID- 29199580
TI  - What Is Ganoderma lucidum in the Molecular Era?
AB  - The scientific name Ganoderma lucidum has long been used in the global medicinal
      mushroom market, and many publications have proven its pharmacological properties
      and chemical components. Although several Ganoderma species have been described
      worldwide as having morphology considerably similar to that of G. lucidum s.
      str., this binomial is still the most frequently used in pharmacological studies.
      However, the use of particularly divergent nomenclature has caused major
      difficulties in the evaluation of the results of pharmacological studies. This
      article is intended to provide a nomenclatural and taxonomic overview of the
      medically important G. lucidum group, that is, G. lucidum aggregate and G.
      lingzhi. Moreover, we evaluate the possibilities of how nomenclatural changes can
      help to avoid misunderstandings in thousands of publications and highlight
      scientifically correct interpretations for future studies.

PMID- 29199581
TI  - Molecular Dynamics and Virtual Screening Analysis of Lanosterol Derivatives from
      Ganoderma Medicinal Mushrooms (Agaricomycetes) as Selective Ligands of Human
      Androgen Receptor.
AB  - Male sex hormones such as testosterone and dihydrotestosterone play important
      roles in several physiological and pathological processes. The biological
      activities of the aforementioned metabolites are mediated by the multidomain
      androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma
      mushroom lanostanoid extracts have previously been shown to exert antiandrogenic
      activity; therefore, this work aims to identify which lanostane derivatives might
      act as selective ligands for AR. Because protein flexibility is of paramount
      importance for ligand binding, different conformations of AR were sampled to
      account for binding modes within a ligand binding site, then subjected to virtual
      screening against a metabolite library. Fifteen Ganoderma lanostanoids were
      selected as AR ligands, according to their calculated binding affinity to this
      nuclear receptor. The results show the relevance of certain structural and
      chemical aspects of our ligands, such as the presence of a ketonic group on C-3,
      which influences the process through which they bind to AR.

PMID- 29199582
TI  - Antidiabetic Properties of the Tiger's Milk Medicinal Mushroom, Lignosus
      rhinocerotis (Agaricomycetes), in Streptozotocin-Induced Diabetic Rats.
AB  - Diabetes mellitus is a major cause of morbidity and mortality worldwide. Although
      scientific evidence supporting its therapeutic efficacy is lacking, the use of
      the tiger's milk mushroom (TGM; Lignosus rhinocerotis), which is native to
      tropical areas such as Malaysia, Indonesia, and the Philippines, has been found
      to contain a very large amount of potential antioxidants. In this study, rats
      were weighed and then intravenously injected with 35 mg/kg streptozotocin (STZ).
      Rats were left for 1 week before blood glucose concentrations were measured to
      determine the onset of diabetes before the next procedure was conducted. Rats
      with blood glucose exceeding 7.0 mmol/L were considered diabetic and were
      included in the experiment. All groups were fed their respective treatments twice
      daily for 2 months throughout the experiment. Antidiabetic and antioxidant
      properties of freeze-dried TGM powder, such as reduced glutathione (GSH),
      superoxide dismutase (SOD), lipid peroxidation (LPO), and catalase (CAT)
      activities, were investigated in liver samples. The biological compounds present
      in the freeze-dried TGM powder was found to exhibit antidiabetic properties by
      significantly reducing elevated blood glucose concentrations to a normal range
      (3.0-7.0 mmol/L) in Sprague-Dawley rats with streptozotocin-induced diabetes, and
      increasing the body weight of the rats. Freeze-dried TGM powder was also found to
      possess antioxidant activity by significantly increasing GSH, CAT, and SOD
      activities while reducing LPO (P < 0.05). THis study shows that freeze-dried TGM
      powder exhibits significant antidiabetic properties and may be a potential
      supplement in ameliorating diabetic complications.

PMID- 29199583
TI  - Antimelanomic Effects of High- and Low-Molecular Weight Bioactive Subfractions
      Isolated from the Mossy Maze Mushroom, Cerrena unicolor (Agaricomycetes).
AB  - Three bioactive fractions isolated from Cerrena unicolor cultures-crude
      endopolysaccharide (c-EPS), laccase, and a subfraction of low-molecular weight
      secondary metabolites-were used to determine potential cytotoxic effects on the
      mouse melanoma B16-F10 cell line (American Type Culture Collection CRL-6475). The
      results obtained prove that all examined fractions exhibited activity against the
      investigated tumor cells. In addition, an evident immunomodulatory effect of the
      c-EPS fraction was observed. Our results show that the levels of 2 cytokines
      (tumor necrosis factor-a and chemokine ligand 2) in mouse inner medullary
      collecting duct mIMCD-3 cells (American Type Culture Collection CRL-2123)
      stimulated by c-EPS were significantly higher. A lipopolysaccharide model was
      used at the same concentration (10 MUg/mL) as a positive control.

PMID- 29199584
TI  - Anti-Inflammation and Lipogenic Inhibition of Taiwanofungus salmonea Mycelium and
      Grifola frondosa Fruiting Body.
AB  - A long-term inflammatory response can cause the development of nonalcoholic
      steatohepatitis (NASH), which is mainly caused by abnormal metabolism of lipids
      in the liver. Taiwanofungus salmonea and Grifola frondosa, which are valuable
      medicinal mushrooms in Taiwan and exhibit many beneficial bioactivities, are used
      to evaluate effects on immune regulation in Raw 264.7 cells and on NASH-related
      responses in Hep G2 cells. According to the results, the production of
      proinflammatory cytokines was effectively decreased, whereas the production of
      interleukin-10 was increased. Lipid accumulation and reactive oxygen species
      production also declined, and free glycerol was released. The expression of
      acetyl-CoA carboxylase, fatty acid synthase, and sterol regulatory element
      binding protein 1c was decreased. These results indicate that T. salmonea and G.
      frondosa are capable of reducing inflammatory responses and ameliorating NASH,
      indicating their potential as hepatoprotective dietary supplements.

PMID- 29199585
TI  - Optimization of Submerged Cultivation Conditions for Production of Big Cup
      Culinary-Medicinal Mushroom Clitocybe maxima (Agaricomycetes) Biomass with
      Significant Antioxidative and Antihyperlipidemic Activities.
AB  - In this study, a large Clitocybe maxima mycelium biomass was obtained by
      submerged cultivation under optimal conditions. Three test samples from
      lyophilized mycelia, including hot water extract (CW) and elutes from solvents
      with different polarity (CA and CB), were combined and used to explore
      antioxidant and antihyper-lipidemic activities in vitro and in vivo. The CA group
      showed the highest DPPH free radical scavenging activity and iron-reducing
      capability at concentrations of 6.0% and 3.0% (w/v), respectively. Further, the
      CA group showed the highest glutathione peroxidase and superoxide dismutase
      activities at a dose of 0.25 mg/kg body weight (CA-0.25 group) in all
      hyperlipidemic hamsters tested. Serum lipid levels (apart from high-density
      lipoprotein cholesterol levels) of hamsters in the CA-0.25 group were lower than
      those of hamsters in the negative control group in antihy-perlipidemic tests.
      Therefore, we believe that extracts from C. maxima mycelia are rich reservoirs of
      antioxidant and antihyperlipidemic activities.

PMID- 29199586
TI  - Health and Risk Assessment by ICP-OES of Heavy Metals and Trace Minerals in
      Commercial Mushrooms Marketed in China.
AB  - The objectives of this study were to investigate mineral profiles of 35 species
      of edible mushrooms collected in China; we compared nutritional values and
      tolerable values with the official recommended daily intakes (RDIs), maximum
      intake limits, and provisional tolerable weekly intakes. A total of 19 minerals
      were detected in edible mushrooms by inductively coupled plasma optical emission
      spectrometry. The results showed that the mushroom samples had a low percentage
      of RDI for the minerals calcium, iron, magnesium, manganese, zinc, potassium, and
      sodium and a relatively higher percentage of RDI for copper and molybdenum. The
      samples also had a very high percentage of RDI for chromium and selenium. The
      level of heavy metals in a majority of the mushrooms was above the limited level,
      and only concentrations of copper and zinc were safe in all mushrooms. In
      conclusion, the mushrooms collected in China are a good source of minerals such
      as molybdenum and selenium but are badly contaminated with aluminum, arsenic,
      cadmium, chromium, and lead.

PMID- 29199587
TI  - Liposome-Based Nanomedicine Therapeutics for Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is a very painful severe autoimmune disease with
      complex pathology characterized by progressive chronic inflammation, and
      devastation of the synovium, cartilage, and other joint-associated structures.
      Significant advances in research in the area of pathophysiology, diagnosis, drug
      development, and targeted delivery have led to improved RA therapy and better
      patient compliance. Targeted drug delivery using liposomal nanomedicines
      significantly alleviate the challenges with conventional anti-RA medications such
      as off-target effects, short biological half-life, poor bioavailability, high
      dose-related toxicity, etc. Liposomal nanomedicines in RA drug targeting offer
      the opportunity for passive targeting [based on size and polyethylene glycol
      (PEG)-ylation-mediated enhanced permeability and retention] and active targeting
      (ligation with antibody or peptides, etc.) and encapsulation of lipophilic,
      hydrophilic drugs, and/or combinational drugs. However, it has been found
      recently that such injectable nanomedicines raise the concern of an adverse
      immune phenomenon called complement activationrelated pseudo allergy (CARPA) and
      failure of therapy on multiple doses due to accelerated body clearance caused
      many by anti-PEG immunoglobulin M. To ensure safety and efficacy of RA therapy,
      these need to be considered along with the common formulation quality parameters.
      Here, we discuss nanotherapeutic targeting in RA therapy using liposomes.
      Liposomal nanoparticles are investigated for individual anti-RA drug categories.
      CARPA issues and pathophysiology with such nanomedicines are also discussed in
      detail.

PMID- 29199588
TI  - Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against
      Cancer and Role of Tumor Microenvironment.
AB  - Cancer is one of the major causes of death worldwide. The silent activation of
      cellular factors responsible for deviation from normal regulatory pathways leads
      to the development of cancer. Nano-biotechnology is a novel drug-delivery system
      with high potential of efficacy and accuracy to target lethal cancers. Various
      biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes,
      dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon
      nanotubes have already been reported for successful targeted cancer treatment.
      NPs are functionalized with different biological molecules, peptides, antibody,
      and protein ligands for targeted drug delivery. These systems include a
      hydrophilic central core, a target-oriented biocompatible outer layer, and a
      middle hydrophobic core where the drug destined to reach target site resides.
      Most of the NPs have the ability to maintain their structural shape and are
      constructed according to the cancer microenvironment. The self-assembling and
      colloidal properties of NPs have caused them to become the best vehicles for
      targeted drug delivery. The tumor microenvironment (TME) plays a major role in
      cancer progression, detection, and treatment. Due to its continuous complex
      behavior, the TME can hinder delivery systems, thus halting cancer treatment.
      Nonetheless, a successful biophysiological interaction between the NPs and the
      TME results in targeted release of drugs. Currently, a number of drugs and NP
      based delivery systems against cancer are in clinical and preclinical trials and
      a few have been approved by Food and Drug Administration (FDA); for example:
      taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances
      about the drugs being used for cancer treatment, their targeted delivery systems
      based on NPs, and the role of TME in this connection.

PMID- 29199590
TI  - Regulating RNA Binding Motif 5 Gene Expression- A Novel Therapeutic Target for
      Lung Cancer.
AB  - RNA-binding motif protein 5 (RBM5), also known as LUCA-15/H37, is a gene that
      maps to human chromosome 3p21.3, a critical region that is deleted in a large
      number of human cancers, of which the majority are lung cancers, and that is
      predicted to contain one or more tumor suppressor genes (TSGs). RBM5 is a tumor
      suppressor gene and is most frequently deleted at the earliest stage of lung
      cancer development. It represents a significant area of recent progress in cancer
      genomic, cytogenetic, and molecular biological research because of its role in
      the induction of cell cycle arrest and apoptosis and the regulation of inhibition
      of in lung cancer metastasis. RBM5 is involved in the suppression of epidermal
      growth factor receptor (EGFR) expression, thus preventing proliferation,
      angiogenesis, invasion, and metastasis of lung cancer. In this way it exhibits
      its tumor suppressive capacity during lung cancer progression. Exploration of
      RBM5's potential importance in inhibiting tumor metastasis includes downstream
      players in the RBM5-mediated metastasis suppressor pathway(s). This review
      highlights the differential expression of the RBM5 tumor suppressor gene which
      impacts cell proliferation and apoptosis control during lung cancer progression.
      Regulating RBM5 expression may be a novel therapeutic target for lung cancer.

PMID- 29199589
TI  - Nanostructured Lipid Carriers: A New Paradigm in Topical Delivery for Dermal and
      Transdermal Applications.
AB  - Topical drug delivery offers many advantages over oral delivery, such as
      avoidance of first-pass metabolism, targeting of the active ingredients for a
      local effect, and patient compliance. However, the achievement of dermal and
      transdermal delivery needs to conciliate difficulties in permeation across skin
      barrier at different levels (skin surface, epidermis, dermis, and hypodermis).
      Nanostructured lipid carriers (NLCs) are recently invented second-generation
      lipidic carriers. The present article intends to provide an insight of
      composition, production, and application of these carriers in topical delivery
      for local and systemic effects. We also discuss key considerations for
      standardization and critical scale-up issues. In the last decade, the volume of
      work on NLCs is reflected in various research reports including patents on the
      development of NLCs, which gives a deeper insight of this emerging field of
      innovation. These carriers have significance because of their uniqueness to
      facilitate the interactions at interfaces with the barrier membranes. NLCs are
      truly a "nanosafe" carrier due to their biodegradable composition and have
      immense promise to overcome the challenges of dermal and transdermal delivery.

PMID- 29199591
TI  - Copine 3 as a Novel Potential Drug Target for Non-Small-Cell Lung Carcinoma.
AB  - Cancer originates from uncontrolled cell division in any part of the body. The
      universal burden of cancer continues to increase, and its treatment remains ever
      more challenging. Among several cancers, lung cancer is the second most common,
      causing 1.6 million deaths worldwide per year. Approximately 85% of lung cancers
      are non-small-cell lung carcinomas (NSCLCs), which are considerably more
      difficult to treat than other cancers. Although various imaging, biopsy, and
      histopathological analyses are widely used, there are no effective or reliable
      biomarkers for detecting early lung carcinoma, particularly NSCLC. For this
      reason, the identification of novel biomarkers to serve as therapeutic targets is
      essential to NSCLC treatment. Copines are a family of membrane-binding proteins
      that are highly conserved, soluble, ubiquitously expressed, calcium dependent,
      and found in variety of eukaryotic organisms. Recent research suggests that they
      may mediate various signaling pathways involved in both tumor progression and
      metastasis. In the copine gene family, copine 3 is a novel player in regulating
      NSCLC metastasis. This review highlights copine 3 as a prognostic marker as well
      as a potential therapeutic target for effective treatment of patients with NSCLC.

PMID- 29199593
TI  - Insulin Protects against Brain Oxidative Stress with an Apparent Effect on
      Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.
AB  - The present study was aimed at assessing the protective effect of insulin against
      doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive
      function for episodic memory was assessed by a novel object recognition task
      (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione,
      and lipid peroxidation-in the hippocampus and frontal cortex were assessed using
      colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50
      days) reduced recognition and discriminative indices in NORT with increased
      oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg,
      i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin
      with an increase in the antioxidant defense systems (SOD, catalase, and GSH).
      Rats treated with combined insulin and DOX spent comparatively more time with the
      novel object when compared to the non-novel objects; however, the observed
      difference was not statistically significant. An apparent improvement (p < 0.26)
      in recognition of the novel object was observed against the damage induced by
      doxorubicin. These results suggest that insulin reduces brain oxidative stress
      and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

PMID- 29199592
TI  - Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of
      Moralbosteroid, a Steroidal Glycoside.
AB  - Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses.
      However, it is now understood that paracetamol can damage the kidneys when
      administered as an overdose. In addition, oxidative stress can play a major role
      in causing nephrotoxicity. This investigation studies the efficacy of
      moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with
      administration of paracetamol. Nephroprotection was studied using two doses of
      the extract. The experimental animals were divided into four groups (n = 6). Two
      groups served as positive and negative controls, respectively, and two received
      the test substances. All of the contents were orally administered. Significant
      reductions in nephrotoxicity and oxidative damages were observed in the treatment
      groups. There was a marked decrease in blood levels of urea, creatinine, and
      lipid peroxidation. Furthermore, it was found that glutathione levels in the
      blood increased dramatically after treatment. Histological findings confirmed the
      potent renoprotective potential of moralbosteroid. This was evidenced by the
      minimized intensity of nephritic cellular destruction. In animal studies,
      moralbosteroid exhibited dose-dependent activity, which is thought to be mediated
      through its antioxidant potential.

PMID- 29199594
TI  - DNA Double-Strand Breaks Caused by Different Microorganisms: A Special Focus on
      Helicobacter pylori.
AB  - The association between inflammation and cancer has long been recognized. Several
      studies have found that different types of tumors develop at sites of chronic
      inflammation. It is stated that over 15%-20% of malignancies worldwide can be
      related to infections caused by viruses, bacteria, and schistosomes. Inflammatory
      conditions are characterized by overexpression of inducible nitric oxide synthase
      (iNOS) and overproduction of nitric oxide/reactive nitrogen species (ROSs/RNSs)
      in epithelial cells. Reactive oxygen species (ROSs) may also lead to cellular
      alterations and eventually to inflammation. A variety of chronic infectious
      diseases can generate steady-state levels of ROSs/RNSs within infected cells and
      possibly lead to different types of DNA lesions. Accumulation of DNA lesions may
      finally lead to mutations that may activate oncogenes or inactivate tumor
      suppressor genes. Helicobacter pylori has been shown to generate ROSs/RNSs,
      induce DNA damage, and lead to chronic inflammation in gastric epithelial cells.
      A limited number of studies have addressed the effects of Helicobacter pylori on
      DNA damage, particularly its impact on single-strand and double-strand DNA
      breaks. This bacterium is classified as a Group I carcinogen by the International
      Agency for Research on Cancer on the basis of numerous animal and epidemiological
      studies. Chronic Helicobacter pylori infection can lead to increased risk of
      gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. This review
      addresses the DNA-damaging and double-strand break-inducing effects of different
      microorganisms and their toxins, specifically focusing on Helicobacter pylori.

PMID- 29199595
TI  - Epidermal Growth Factor Receptor Tyrosine Kinase: A Potential Target in Treatment
      of Non-Small-Cell Lung Carcinoma.
AB  - Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung
      cancers are of the non-small-cell variety, which includes squamous cell
      carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer
      progression is a requisite for determining which management approach-surgery,
      chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic
      approaches with antiangiogenic monoclonal antibodies or tyrosine kinase
      inhibitors are one option if tumors harbor oncogene mutations. Another, newer
      approach is directed against cancer-specific molecules and signaling pathways and
      thus has more limited nonspecific toxicities. This approach targets the epidermal
      growth factor receptor (EGFR, HER-1/ErbB1), a receptor tyrosine kinase of the
      ErbB family, which consists of four closely related receptors: HER-1/ErbB1, HER
      2/neu/ErbB2, HER-3/ErbB3, and HER-4/ErbB4. Because EGFR is expressed at high
      levels on the surface of some cancer cells, it has been recognized as an
      effective anticancer target. EGFR-targeted therapies include monoclonal
      antibodies (mAbs) and small-molecule tyrosine kinase inhibitors. Tyrosine kinases
      are an especially important target because they play an important role in the
      modulation of growth factor signaling. This review highlights various classes of
      synthetically derived molecules that have been reported in the last few years as
      potential EGFR-TK inhibitors (TKIs) and their targeted therapies in NSCLC, along
      with effective strategies for overcoming EGFR-TKI resistance and efforts to
      develop a novel potent EGFR-TKI as an efficient target of NSCLC treatment in the
      foreseeable future.

PMID- 29199596
TI  - Insulin Combined with Glucose Improves Spatial Learning and Memory in Aluminum
      Chloride-Induced Dementia in Rats.
AB  - Therapeutic intervention using drugs against Alzheimer disease is curative
      clinically. At present, there are no reports on the curative role of insulin in
      chronic models of dementia. We evaluated the curative role of insulin and its
      combination with glucose in dementia. We also investigated the impact of
      treatments on blood glucose to correlate with cognitive deficit. Further, we
      analyzed the interaction of treatments with the cholinergic system and oxidative
      stress in memory centers (i.e., hippocampus and frontal cortex). The antidementia
      activity of insulin was assessed against aluminum chloride (AlCl3)-induced
      dementia in rats. Behavioral parameters (Morris water maze test) along with
      biochemical parameters (Hippocampus and frontal cortex) such as
      acetylcholinesterase (AChE), catalase, and glutathione (GSH) levels were assessed
      to correlate cognitive function with cholinergic transmission and oxidative
      stress. Rats administered insulin and glucose showed improved cognitive function
      in the Morris water maze test. The combination corrected the diminished level of
      antioxidant enzymes such as catalase and GSH in the hippocampus and frontal
      cortex.Combined administration of insulin and glucose to aluminum-treated rats
      did not inhibit the aluminum action on the acetylcholinesterase enzyme. No
      significant changes were observed in blood glucose levels between the treatment
      groups.

PMID- 29199598
TI  - Transcranial Magnetic Stimulation in Migraine: A New Therapy and New Insights
      into Pathogenesis.
AB  - Transcranial magnetic stimulation (TMS) was first found to be effective in acute
      migraine 12 years ago, and subsequent studies have confirmed this benefit in
      approximately two -thirds of treated patients. High response rate, ease of
      application, and freedom from adverse effects combine to make TMS a natural front
      line treatment for migraine, and its use should therefore be encouraged. In
      relation to the pathogenesis of migraine, the prompt relief of symptoms often
      observed with TMS is considered incompatible with an underlying neuroinflammatory
      process and with spreading depression as a cause of aura. Instead, the available
      evidence points to hyperexcitability of cortical neurons as the immediate cause
      of headache and any associated symptoms, although the factor(s) leading up to the
      hyperexcitability remain unclear.

PMID- 29199599
TI  - Air Pollution and Cardiovascular Disease: A Review.
AB  - Air pollution is comprised of different compounds and particulate matter (PM) of
      sizes 2.5 and 10 MUm, with the former size posing the greatest danger to humans.
      Evidence suggests that the global rise in air pollution levels during the past
      century is correlated with the increased incidence of diseases of the
      cardiovascular system. On a global scale, 7 million individuals died as a result
      of the effects of air pollution in 2012. Air pollution leads to tremendous
      amounts of financial burden (in 2010, $16 trillion in the US and Europe) on the
      health-care system. The severity of effects experienced by varying populations
      due to air pollution can differ due to locale, length of exposure, weather
      conditions, residential proximity to major highways or factories, and soil
      aridity. Pollutants affect the heart, blood vessels, and blood at a molecular
      level through proinflammatory or oxidative stress response, autonomic nervous
      system imbalance, and the direct permeation of harmful compounds into the tissue.
      The dysfunction of cells and biological processes of the cardiovascular system
      due to PM leads to an increased prevalence of cardiovascular diseases (CVDs) such
      as atherosclerosis, hypertension, myocardial infarction, thrombosis, and
      restricted valve motion. Studies in countries such as China have shown an
      increase of 0.25% in ischemic heart disease (IHD) mortality and a 0.27% increase
      in IHD morbidity due to a 10 MUg/m3 increase in PM. In a study conducted in the
      US, PM2.5 concentrations ranged from 9.2-22.6 MUg/m3, and every 5-MUg/m3 increase
      in PM2.5 caused coronary calcification to increase by 4.1 Agatston units/yr.
      Studies on traffic-related air pollution found that nonhypertensive participants
      residing within 100 m of major roadways experienced an increase in systolic (0.35
      mmHg) and diastolic (0.22 mmHg) blood pressure as a result of increases in
      traffic. The progression of CVD due to pollution has been found to fluctuate
      within individuals based on age, gender, location of exercise, smoking,
      pregnancy, diabetes, preexisting cardiovascular or pulmonary diseases, and other
      factors. Considering the number of individuals affected by pollution on a daily
      basis and the burden that this places on society through the health-care system,
      immediate preventive measures are needed to address these problems. Increased
      knowledge about the widespread effects of pollution on human physiological
      systems should aid in remediating the problem across the globe. Biomedical
      engineers can have a great positive impact in developing better instrumentation
      to measure discrete pollutants and characterizing their harmful effects on
      physiological systems.

PMID- 29199597
TI  - Hepatocellular Carcinoma and Possible Chemical and Biological Causes: A Review.
AB  - The development of hepatocellular carcinoma (HCC) is a multistep process. In HCC,
      progressive and morphologically distinct preneoplastic lesions/alterations
      associated with chronic liver injury, inflammation, hepatocellular
      degeneration/regeneration, necrosis, and small-cell dysplasia can be observed.
      The incidence of HCC exhibits regional and ethnic differences. Several cytotoxic
      and DNA-damaging chemicals are suggested to be the underlying causes of HCC-for
      example, acrylamide, perfluorooctanoic acid (PFOA), polychlorinated biphenyls
      (PCBs), benzo(a)pyrene (BaP), perfluorinated chemicals (PFCs), vinyl chloride
      monomer (VCM), and dietary contaminants (aflatoxins, ochratoxins). Also suggested
      are substances of abuse (alcohol) and biological agents, such as hepatitis B and
      C and human immunodeficiency virus 1 (HIV-1). These can act through genetic
      and/or epigenetic mechanisms. This review will shortly address the genetic and
      epigenetic mechanisms of HCC and focus on cytotoxic and DNA-damaging chemicals
      and biological agents, exposure to which are suggested to lead to HCC initiation,
      promotion, and/or progression.

PMID- 29199600
TI  - The Migraine Aura: A Problem for Vision Theory?
AB  - The scintillating zigzag pattern that a migraine patient may see as an illusion
      before the onset of headache offers a unique investigative approach to visual
      mechanisms. The likeliest interpretation of these zigzags is that they are the
      spontaneous discharges of the orientation-selective neurons first described in
      the striate cortex by Hubel and Wiesel (Hubel DH, Wiesel TN. Receptive fields,
      binocular interaction and functional architecture in the cat's visual cortex. J
      Physiol (Lond). 1962 Jan;160:106-54; and Hubel DH, Wiesel TN. Receptive fields
      and functional architecture of monkey striate cortex. J Physiol (London). 1968
      Mar;195(1):215-43). Although these cells appear to lie in rows in V1, as Hubel
      and Wiesel found, very few angles in the visual field are represented; this, and
      the coarseness of the representation, makes it unlikely that the cells act as
      feature detectors. The orientation-selective cells could, however, monitor the
      amount of light falling on the retina and thereby enable color constancy to be
      achieved. The cells may also serve as coarse movement detectors. The new model of
      cell organization in human V1 enables us to determine the approximate sizes of
      the receptive fields of the orientation-selective cells.

PMID- 29199601
TI  - A Review of Sensing Systems and Their Need for Environmental Water Monitoring.
AB  - Water is a valuable natural resource and is needed to sustain human life. Water
      pollution significantly jeopardizes clean drinking water supplies, it is
      hazardous to human health, and it inhibits economic development. Well-designed
      sensors that can continuously monitor water quality during transport and identify
      contaminants in the watershed help effectively control pollution and thereby
      manage water resources. However, the commercially available sensors are expensive
      and require frequent maintenance. These limitations often make these sensors
      inadequate for continuous water monitoring applications. This review evaluates
      many sensors based on colorimetric, electrochemical, and optical sensors. Sensors
      suitable for estimating the amount of dissolved oxygen, nitrates, chlorine, and
      phosphates are presented. A review of recently developed high quality sensors for
      measuring the previously mentioned components of water is also presented. Future
      directions in this area of developing high quality sensors for water monitoring
      are discussed.

PMID- 29199602
TI  - Air Pollution's Effects on the Human Respiratory System.
AB  - The World Health Organization defines air pollution as "any chemical, physical or
      biological agent that modifies the natural characteristics of the atmosphere."
      The most common pollutants include particulate matter, carbon monoxide, ozone,
      nitrogen oxide, and sulfur dioxide. The two types of air pollution, indoor and
      ambient, both contribute to a host of cardiac and respiratory illnesses. Exposure
      to excess levels of air pollution is significantly associated with a variety of
      acute and chronic respiratory illnesses, such as chronic obstructive pulmonary
      disease, asthma, respiratory allergies, and lung cancer. The effects of air
      pollution disproportionately impact the extremes of the age distribution, perhaps
      due to altered immune responses. Athletes and those who exercise outdoors are at
      greater risk for the respiratory effects of air pollution. This article discusses
      the epidemiology, types of respiratory diseases, and mechanisms involved in
      exposure to excess levels of air pollution. Biomedical engineering can contribute
      to the identification of air pollutants through the design of novel
      instrumentation using materials based on nanotechnology. Mathematical models can
      also be developed to characterize the physiological effects of air pollution.

PMID- 29199603
TI  - Posture and Loading in the Pathomechanics of Carpal Tunnel Syndrome: A Review.
AB  - Carpal tunnel syndrome is a neuropathy of the median nerve at the wrist, and
      represents the most common peripheral neuropathy. It has long been an issue in
      the workplace because of healthcare costs and loss of productivity. The two main
      pathomechanisms of carpal tunnel syndrome include increased hydrostatic pressure
      within the carpal tunnel (carpal tunnel pressure) and contact stress (or
      impingement). As most cases of carpal tunnel syndrome in the workplace are
      labelled "idiopathic", a clear understanding of the physical parameters that may
      act as pathomechanisms is critical for its prevention. The aim of this review is
      to examine and quantify the influence of posture and loading factors on the
      increase of carpal tunnel pressure and median nerve contact stress. Forearm,
      wrist, and finger postures, as well as fingertip force have significant effects
      on carpal tunnel pressure. Contact stress on the median nerve is mainly a product
      of wrist posture and musculotendinous loading. Anatomical and musculoskeletal
      sources have been proposed to explain these effects. This critical review
      provides an improved understanding of pathomechanisms and etiology underlying
      carpal tunnel syndrome.

PMID- 29199604
TI  - miRNA: A Diagnostic and Therapeutic Tool for Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is fatal disease and one of the major
      causes of death among cancer patients. Diagnosis of PDAC during the early stages
      of cancer using ultrasounds and blood tests is difficult and chemotherapies alone
      for treating cancers are not very effective. MicroRNAs (miRNAs), small non-coding
      RNAs that alter the expression of genes in many processes, have been identified
      to play a significant role in pancreatic cancer regulation. miRNAs are classified
      as oncomiRs (tumor inducers) and tumor suppressor miRNAs. It has been found that
      miRNAs are regulated very differently in serum and cells surrounding cancer cells
      and within cancerous cells. miRNAs regulate cancer cell proliferation, invasion,
      and apoptosis by being differently up-regulated or downregulated and affecting
      the expression of genes involved in cancer cell signaling. Therefore, miRNAs can
      be used as effective diagnostic markers and drug targets for therapy. In this
      review, we describe the most recent studies performed for understanding molecular
      mechanisms and gene regulations in PDAC and their utility for diagnosis and
      therapy.

PMID- 29199605
TI  - Modeling Mesenchymal Stem Cells in TMJ Rheumatoid Arthritis and Osteoarthritis
      Therapy.
AB  - Stem cells have self-renewal capacity and an ability to differentiate into
      particular cell types generating mature cells. Mesenchymal stem cells (MSCs) have
      a significant role in tissue homeostasis, which leads into tissue regeneration.
      MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell
      lineages. MSCs are also believed to have therapeutic power over temporomandibular
      joint (TMJ) disorders (TMDs). The most common type of TMD is articular disc
      displacement, which induces progressive degenerative changes. These changes lead
      to rheumatoid arthritis or osteoarthritis. In this review, use of human
      mesenchymal cells (hMSCs) for therapeutic treatment of inflammatory diseases of
      TMJ is discussed.

PMID- 29199606
TI  - Association of IL-6 -597 G/A Polymorphism with Cancer Risk: Evidence from a Meta
      Analysis.
AB  - Although it has been suggested that the interleukin-6(IL-6) gene -597G/A
      polymorphism may be a risk factor for cancer, the conclusions from previous
      studies are inconsistent. To clarify the precise interrelation, we performed a
      comprehensive meta-analysis of 6 case-control studies involving 1,605 subjects
      (706 cases and 899 controls). The overall results showed no significant
      association between the IL6 -597G/A polymorphism and cancer risk in the overall
      population (CC vs GG: OR = 2.38, 95% CI = 0.62-9.14; CG vs GG: OR = 1.23, 95% CI
      = 0.66-2.27; dominant model: OR = 1.32, 95% CI = 0.63-2.79; recessive model: OR =
      1.93, 95% CI = 0.72-v5.17). Subgroup analysis by ethnicity and cancer type
      yielded the same result. Therefore, the current evidence from this meta-analysis
      did not support the hypothesis of IL-6 -597G/A polymorphism as a risk factor of
      cancer. Conclusive evidence on the effects of this variant in cancer should be
      addressed in future studies.

PMID- 29199607
TI  - Transposable Elements (Human Endogenous Retroviruses) in Cancer.
AB  - Transposable elements (TEs) have shown a great significance in regulatory
      elements research, being responsible for different types of cancers. They are
      divided into three classes on the basis of their mode of transposition,
      structural properties, and their homology with DNA sequence. In evaluating their
      role in cancers and other pathologies, researchers have found extensive evidence
      of their involvement. TEs can also be used as genetic markers for cancers and
      help in identifying potential therapeutic targets. There have been advancements
      in the management of hepatocellular carcinoma using TEs as regulatory components
      involved in the cancer's pathogenesis.

PMID- 29199608
TI  - Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes
      Mellitus.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine that decisively induces the
      development of insulin resistance and pathogenesis of type 2 diabetes mellitus
      (T2DM) through the generation of inflammation by controlling differentiation,
      migration, proliferation, and cell apoptosis. The presence of IL-6 in tissues is
      a normal consequence, but its irregular production and long-term exposure leads
      to the development of inflammation, which induces insulin resistance and overt
      T2DM. There is a mechanistic relationship between the stimulation of IL-6 and
      insulin resistance. IL-6 causes insulin resistance by impairing the
      phosphorylation of insulin receptor and insulin receptor substrate-1 by inducing
      the expression of SOCS-3, a potential inhibitor of insulin signaling. In this
      article, we have briefly described how IL-6 induces the insulin resistance and
      pathogenesis of T2DM. The prevention of inflammatory disorders by blocking IL-6
      and IL-6 signaling may be an effective strategy for the treatment of insulin
      resistance and T2DM.

PMID- 29199609
TI  - TSG101: Tumor Susceptibility Gene 101 (tsg101) Product-Role in Therapy Against
      HIV/AIDS.
AB  - HIV infection presents a major community health hazard, partially because the HIV
      virus is capable of evading antiretroviral therapies. Most anti-HIV drugs were
      intended to target virus-encoded mechanisms; however, some host-encoded molecules
      comparatively execute a vital role in the life cycle of virus. Thus, these might
      be considered as target sites for antiviral agents. TSG101 is important among
      these antiviral therapies because, as a cytoplasmic molecule, it facilitates
      viral budding and release. In this review, HIV-infected cells have TSG101 on
      their surface and thus can be used in antibody-based therapies. The development
      of a monoclonal antibody CB8-2 lessens the assembly of viruses from infected
      cells. This mechanism represents the potential use of TSG101-directed antibodies
      to fight against AIDS.

PMID- 29199610
TI  - Potential Utility of N-acetylcysteine for Treating Mustard Lung.
AB  - More than a century after the introduction of sulfur mustard (SM), as a chemical
      warfare agent, it has affected thousands of military and civilians on several
      occasions. The most notable toxic effects of this easily produced chemical, are
      lung damage ranges from necrotic, hemorrhagic, and infectious acute-lung injury
      to chronic conditions (i.e., mustard lung). While there is no definite treatment
      for individuals exposed to sulfur mustard, corticosteroids, mucolytics,
      bronchodilators, antibiotics, immunosuppressive medicines, and magnesium are
      being used to help victims. In the pathophysiology of SM-induced lung conditions,
      oxidative stress and inflammation play undeniable roles; thus, N-acetyl-L
      cysteine (NAC) has been used as a treatment. In this narrative review article, we
      discuss the mechanisms involved in SM-induced lung damage along with the
      properties of NAC that can help patients recover from these deleterious effects.

PMID- 29199611
TI  - Association of ERCC1 Polymorphisms with the Risk of Colorectal Cancer: A Meta
      Analysis.
AB  - The ERCC1 enzyme in the nucleotide excision repair (NER) pathway plays a vital
      role in DNA repair. Numerous epidemiological studies have evaluated the
      association between ERCC1 polymorphisms and the risk of colorectal cancer (CRC),
      with conflicting results. To evaluate the potential associations, we conducted a
      meta-analysis. Eligible studies were identified by searching electronic
      databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to
      assess the associations between ERCC1 polymorphisms and CRC risk. The meta
      analysis results revealed significant associations between ERCC1 rs3212986 and
      rs2298881 polymorphisms and CRC risk (rs3212986 GG vs CC: OR = 1.66, 95% CI =
      1.13-2.44; CG vs CC: OR = 1.12, 95% CI = 0.82-1.55; the dominant model: OR =
      1.21, 95% CI = 0.86-1.71; the recessive model: OR = 1.59, 95% CI = 1.09-2.31;
      rs2298881 CC vs. AA: OR = 2.04, 95% CI = 1.29-3.23; AC vs. AA: OR = 1.19, 95% CI
      = 0.91-1.56; the dominant model: OR = 1.33, 95% CI = 1.04-1.72; the recessive
      model: OR = 1.91, 95% CI = 1.22-3.00). However, no association with CRC risk was
      identified for ERCC1 polymorphisms rs11615 and rs2276466. In conclusion, these
      findings identified no association between rs11615 and rs2276466 polymorphisms
      and CRC susceptibility, but the data indicate that ERCC1 rs3212986 and rs2298881
      polymorphisms may increase susceptibility to CRC. Large and well-designed studies
      are needed to further validate our findings.

PMID- 29199612
TI  - Involvement of Different Genes Expressions during Immunological and Inflammatory
      Responses in Vitiligo.
AB  - Vitiligo is a condition of the skin distinguished by hypo-pigmentation. Etiology
      of this disorder is unknown, and several theories and mechanisms have been
      hypothesized. The inflammatory response in vitiligo is thought to be mediated by
      polymorphism in genes such as FOXP3, ACE, APE, GSTP1, TLR, SOD, CTLA-4, TAP/LMP
      gene cluster, etc. Theories including reactive oxygen species model, Nrf2
      antioxidant response element (ARE) pathway, WNT pathway, tyrosinase activity,
      biochemical, molecular, and cellular alterations have been hypothesized to
      explain vitiligo pathogenesis. Melanosomal proteins are involved in antigen
      processing. The antigens are expressed to the T-cells in the form of peptides
      with HLA class II molecules. T-cells are activated in response to the discharge
      of co-stimulatory molecules such as LFA-3 as well as ICAM-1. An adaptive immune
      response is thus elicited, and the melanocytes eventually die or start
      malfunctioning and the skin undergoes hypo-pigmentation. IFN-gamma is known to be
      a melanocyte inhibitor of paracrine origin; it is clearly involved in the early
      onset of symptoms of vitiligo disease. The surge in the IFN-gamma levels mediates
      augmented expression of ICAM-1 molecule on the melanocytes, thereby establishing
      cytokine-mediated destruction of melanocytes. Mainly, mediators released by
      melanocytes and the functionality of keratinocytes decrease the disease activity.
      Such mediators include ET-1 as well as SCF, increase the pigmentation
      particularly when a patient is given with the UVB treatment. By scavenging ROS
      and screening UV radiation, melanin limits the damage caused to the cutaneous
      cells by UV radiation. Various immune responses play important roles in vitiligo.

PMID- 29199613
TI  - Current Retrograde Approach Is Unfavorable to Long-Term Clinical Outcomes after
      Percutaneous Coronary Intervention for Chronic Total Occlusion.
AB  - Surgeons currently use two different wire-based approaches to recanalize coronary
      chronic total occlusion (CTO): antegrade and retrograde. It has been demonstrated
      that the retrograde approach has improved the procedural success rate, but it
      remains unclear whether the retrograde approach is better than the antegrade
      approach for the long term. In this study, we enrolled a total of 187 patients
      with a diagnosis of CTOs. We evaluated the baseline characteristics of these
      patients and performed percutaneous coronary intervention to treat their problems
      by using either antegrade or retrograde approaches and different techniques in
      both groups. In the antegrade approach, we used three techniques: single wire,
      parallel wire, and side branch. The techniques in retrograde included kissing
      wire, controlled antegrade and retrograde subintimal tracking (CART), and reverse
      CART. We found that the antegrade and retrograde groups had similar baseline
      characteristics, with a few minor differences. Most importantly, we found that
      within 1 yr of the recanalizing procedure, the restenosis rate and major adverse
      cardiac event rate of the retrograde group were significantly higher compared to
      the antegrade group. We conclude that the retrograde approach may not be as
      beneficial as the antegrade approach for long-term clinical outcomes.

PMID- 29199614
TI  - Electromagnetic Response of Bones Adjacent to the Dental Root Before and After
      Dental Implantation.
AB  - The aim of this study was relative variation quantification of the total electric
      field (EF) sum in a region very close to a dental root of the first molar tooth
      for two different materials: dentine (before implantation) and titanium (present
      in a screw after implantation), due to development of electrical charges
      generated by chewing force on the tooth. Because bone is a piezoelectric
      material, mechanical strain that is generated by chewing force on bone adjacent
      to the dental root produces electrical charges. Relative variations in the EF sum
      values with distance of nodes from the centerline of the root was observed for
      both cases and studied for two different boundary voltage conditions. Simulation
      and analysis were performed using the commercial finite-element analysis package
      ANSYS14. The detailed convergence analysis validated the effectiveness and
      accuracy of finite-element simulations. Before and after implantation, a
      significant variation in generation of electric charges at adjacent bone of the
      dental root was observed. We found that the differences in stress generation at
      the adjacent bone for those cases were just 5%, on average.

PMID- 29199615
TI  - The Role of Macrophages in the Biological Reaction to Wear Debris from Artificial
      Joints.
AB  - Normal usage of total joint replacements results in the production of wear debris
      and other byproducts. In particular, polyethylene particles are heavily involved
      in the stimulation of local and systemic biological reactions resulting in
      chronic inflammation, periprosthetic bone resorption (osteolysis), and eventually
      implant loosening. As sentinels of the innate immune system, cells of the
      monocyte/macrophage lineage initiate the inflammatory cascade that lead to
      osteolysis. The biological processes involved are complex, based on the unique
      properties of the monocytes/macrophages, including sensing, chemotaxis,
      phagocytosis, and adaptive stimulation. The interaction with wear debris triggers
      the release of pro-inflammatory factors such as tumor necrosis factor-alpha,
      interleukin-1, and others; pro-osteoclastic factors such as RANKL; and chemokines
      such as MCP-1 and MIP-1, all of which are crucial to the recruitment, migration,
      differentiation, and ultimately activation of bone-resorbing osteoclasts. In
      parallel, other distinct macrophage populations inhibit inflammation and mitigate
      its consequences on the bone-implant interface. Here, the role of the
      monocyte/macrophage cell lineage in the initiation and maintenance of the host
      inflammatory response to wear debris and subsequent periprosthetic osteolysis is
      presented.

PMID- 29199616
TI  - Very Large Diameter Polymer Acetabular Liners Show Promising Wear Simulator
      Results.
AB  - Thinner and larger acetabular components are more stable and are useful for
      resurfacing. This study performed wear simulator tests of the largest
      polyurethane (PUR) and highly cross-linked polyethylene (XLPE) liners available.
      The results were compared with conventional polyethylene (ConvPE) to determine
      wear, survivorship, wear debris particles generated, and oxidative degradation.
      Two-piece acetabular components with a 4-mm poly liner, a 2-mm metal backing, and
      1 mm of porous coating with an inner diameter of 51 mm were tested. Cobalt
      chromium (CoCr) and titanium nitride (TiN)-coated titanium- resurfacing femoral
      components were counter-face surfaces. Acetabular components were tested at 45
      degrees  and 65 degrees  inclinations, with both 300 MUm and an increase of 1 mm
      in radial clearance. After 30 million cycles, PUR had 56% (p < 0.001) less wear
      and cross-linked had 93% (p < 0.001) less wear than ConvPE. TiN-coated femoral
      implants had 23% less wear than CoCr when used with cross-linked polyethylene.
      Wear increased by 16% at 65 degrees  and by 19% when radial clearance increased
      with cross-linked polyethylene. Polymethylmethacrylate debris ultimately failed
      ConvPE, but not the cross-linked polyethylene or PUR. XLPE acetabular liners are
      compatible with >20 years of expected use in active patients.

PMID- 29199617
TI  - Can Both Cruciate Ligaments Be Preserved in Knee Arthroplasty? Eight- to Nine
      Year Follow-Up of a Bicompartmental Knee Replacement.
AB  - Preservation of native knee anatomy may confer improved patient satisfaction, as
      suggested by patient satisfaction scores in unicondylar versus total knee
      replacement. Bicompartmental knee replacement (BKR) implants similarly promote
      native tissue preservation. We retrospectively reviewed 42 consecutive patients
      who underwent BKR from 2006 to 2007. Outcome measures were evaluated. At an
      average follow-up of 103 months (range 87-110), 34/42 (81%) of implants survived.
      Among the retained implants, the Knee Society Score (KSS) grade was excellent in
      26/34 (76.5%), good in 5/34 (14.7%), fair in 3/34 (8.8%), and poor in 0/34 (0%)
      of cases. Midterm results of BKR demonstrated 81% survival and 76% with excellent
      KSS grading. Despite a 20% revision rate at the short-term follow-up, the
      retained implants functioned well at the midterm follow-up.

PMID- 29199618
TI  - Clinical and Radiographic Evaluation of Demineralized Freeze-Dried Cancellous
      Block Allograft for Ridge Augmentation: A Pilot Study.
AB  - Bone resorption after tooth extraction is a common problem in implant dentistry.
      Allografts are one of the therapeutic techniques used to reconstruct the
      deficient ridge. Although this technique eliminates the need for a surgical donor
      site, it has yielded contradictory results. The aim of the present pilot study
      was to evaluate the clinical and radiographic results of the use of demineralized
      freeze-dried cancellous block allografts (DFDCBAs) in lateral ridge augmentation.
      Seven patients were included in this study. Lateral reconstruction of bone was
      performed using DFDCBA with stabilizing screws and resorbable collagen membranes.
      The ridge width was initially measured during the augmentation surgery. A second
      measurement was taken 6 months later at the time of implant placement. In
      addition, cone bean computed tomography images were used at both baseline and at
      6-month reentry for measuring the width of bone by applying an acrylic stent with
      a radiopaque marker at the edentulous area. Paired t test was used to evaluate
      the statistical differences. The mean increase in the clinical and radiographic
      ridge widths were 1.70 +/- 1.90 and 1.28 +/- 1.52 mm, respectively, which were
      not statistically significant (P = 0.56 and P = 0.067, respectively). The results
      showed that the use of DFDCBAs in conjunction with resorbable membrane does not
      yield predictable results in the reconstruction of ridge width deficiencies.

PMID- 29199619
TI  - Unusual Complication after Intramedullary Nailing of an Intertrochanteric
      Fracture.
AB  - Intramedullary nails have gained popularity for the treatment of
      intertrochanteric fractures. Cephalic screw cutout, non-union, nail breakage,
      intraoperative fractures, and peri-implant fractures are complications of these
      implants and have been well described. This case report describes an unusual
      complication in an 89-year-old woman presenting with a femoral neck fracture with
      an intramedullary nail in place without implant failure or non-union after having
      been successfully treated three years previously for an intertrochanteric
      fracture.

PMID- 29199621
TI  - Static, Dynamic, and Fatigue Finite Element Analysis of Dental Implants with
      Different Thread Designs.
AB  - In this study, we aimed to design an ideal dental implant with respect to stress
      and strain patterns on the surrounding cortical and cancellous bones. The effects
      of static loading on dental implants have been previously assessed, but the
      impact of dynamic loading and fatigue analysis has not been well studied. We
      evaluated static, dynamic, and fatigue behaviors of dental implants to fully
      understand the mechanism and acquire a more realistic perspective of the process.
      In this study, we analyzed three models of a tapered dental implant: model 1 had
      V-shaped threads; model 2 had microthreads in the upper area and V-shaped threads
      in the rest of the body; model 3 had reverse buttress threads in all areas. Two
      types of loading conditions were simulated in a finite element model, and stress
      and strain patterns in the surrounding bone were evaluated. Minimum von Mises
      stresses of cortical bone were recorded in model 2. The values for a 100-N load
      with a 25 degrees  angle were 44.5 and 47.4 MPa for static and dynamic analyses,
      respectively. Considering the obtained stress and strain patterns, we conclude
      that a tapered implant with microthreads in the upper area and V-shaped threads
      in the rest of the body is preferred for best uniform stress distribution in both
      static and dynamic analyses.

PMID- 29199620
TI  - Eosinophilic Metallosis: A Newly Described Entity in Failed Metal-on-Metal
      Arthroplasty.
AB  - In recent years, metal-on-metal (MoM) orthopaedic implants have been associated
      with significant adverse tissue reactions, prompting revision surgeries and
      recalls by manufacturers. Adverse tissue reactions consist of a wide range of
      pathologic findings but are generally characterized by a histiocytic reaction to
      metal debris, with or without an inflammatory response. Inflammation is generally
      that of a lymphocytic infiltration that prompts concern of an immune reaction.
      Only occasionally have eosinophils been documented-never as a marked infiltrate.
      In this article, we present the first histologic description of a dominant
      eosinophilic infiltrate associated with MoM arthroplasty. In our case report, the
      patient is a 53-year-old woman who presented with recurrent fluid collections
      surrounding the hip after a MoM total hip arthroplasty. At the time of surgical
      revision, tissue samples were taken and found to consist of lymphocytes and a
      prominent infiltrating eosinophilia. To our knowledge, no factors predictive of
      this type of tissue response have been identified, and its significance remains
      unclear despite ongoing research about the nature of the immune response to
      metal. Future work may help to elucidate whether the type and significance of
      this response can be predicted preoperatively and modulated, if necessary,
      postoperatively.

PMID- 29199622
TI  - Bifid Median Nerve Complete Transection at the Wrist.
AB  - A 17-yr-old male patient was admitted with a transverse sharp transection caused
      by broken glass at the volar aspect of his left wrist. Clinical examination
      showed loss of sensation at the distribution of the median nerve to the thumb,
      index, and middle finger and an inability to flex the middle finger. Under
      regional anesthesia and a high humerus tourniquet, surgical exploration of the
      wound with binocular loupe magnification showed a bifid median nerve with a
      persistent thin median artery running between the two nerve trunks. The bifid
      median nerve was sharply and transversely transected, slightly proximal to the
      transverse carpal ligament. The palmaris longus tendon and the flexor digitorum
      superficialis tendon of the middle finger were also cut. The flexor digitorum
      tendon was sutured with a two-strand technique augmented with a running
      epitendinous suture. The two trunks of the bifid median nerve were repaired
      separately using microsurgical technique and 8-0 nylon epineural sutures.
      Postoperatively, the hand was immobilized in a palmar short-arm splint that was
      removed at 40 d. A progressive Tinel sign was evident 30 d postoperatively. At 3
      mo, the patient experienced light touch sensation at the tip of the index and
      middle fingers. At the last follow-up, 2.5 yr after his injury, the patient has
      complete nerve functional recovery without atrophy of the thenar muscles and with
      strong thumb opposition.

PMID- 29199623
TI  - Arthroscopic Finding of an Extra-Articular Loose Body in the Subacromial Space:
      Case Report Presentation and Literature Review.
AB  - Loose bodies are pieces of soft tissue that run free within a body cavity,
      typically in the synovium; loose bodies outside of synovial cavities are very
      rare. This case study demonstrates such an instance occurring in the subacromial
      space, which is especially unusual. We report on it coupled with an analysis of
      the literature of known cases that have occurred previously. A 55-year old right
      hand-dominant female patient presented with left shoulder pain. She had injured
      her left shoulder 7 yr previously and had achieved adequate pain and symptomatic
      control with physiotherapy. A magnetic resonance imaging scan demonstrated
      subacromial subdeltoid bursitis with a large subacromial spur, a bulky
      acromioclavicular (AC) joint, and a partial tear of the supraspinatous tendon.
      The patient subsequently underwent shoulder arthroscopy for subacromial
      decompression and AC joint excision. Arthroscopy demonstrated a suspected
      impingement of the rotator cuff in the subacromial space, bursitis, and a
      prominent acromion that limited the subacromial space (bigliani, type III), but
      during the procedure a detached white mass was discovered in the subacromial
      bursa. After histological analysis, the mass showed osteocartilagenous tissue,
      consistent with a loose body. Following the procedure, there were no
      complications, and the patient's symptoms gradually resolved. Extraarticular
      loose bodies are extremely rare, especially in the subacromial bursa. Reported
      cases have all been associated with either traumatic or degenerative shoulder
      pathology, and the diagnosis was commonly established incidentally on
      arthroscopy. Cases were managed with removal during the same procedure.
      Arthroscopic removal of loose bodies and bursa debridement, good options for
      treatment of loose bodies in the subacromial space, can result in good function.

PMID- 29199624
TI  - A New Design for Maximum Conformity of Total Knee Prosthesis to Femur and Tibia.
AB  - Total knee arthroplasty (TKA) is a common procedure for treating patients with
      excessively arthritic knees. Nonetheless, early failure of TKA may occur in the
      first 5 yr, and up to 20% of TKA procedures can fail after 20 yr. In this study,
      a new anatomic prosthesis was designed to provide maximum conformity to knee
      bones and produce less stress and strain, in an effort to avoid possible failure
      of the prosthesis. Anatomical and conventional knee models were compared on the
      basis of both geometric conformity and stress and strain results obtained from
      finite element analysis. To compare geometric conformity, anatomic prosthesis
      components were manufactured by laser melting, and conventional prosthesis
      components were fixed to sawbone knee models. The anatomical model yielded up to
      50% less contact pressure at the insert, which may indicate potential for reduced
      wear between insert and femur components. This model also resulted in less
      principal strain value at the tibial component, considered to be an important
      parameter to indicate loosening. The anatomical model with a new femur component
      in the anterior cortex design also yielded less stress at the femoral cortex,
      when compared to the conventional model. The findings in this study suggest that
      the anatomic prosthesis model may be a better design alternative to conventional
      knee prostheses in terms of wear, aseptic loosening, and normal joint
      biomechanics.

PMID- 29199625
TI  - Preface.

PMID- 29199626
TI  - Reliability and Validity of Nonsymbolic and Symbolic Comparison Tasks in School
      Aged Children.
AB  - Basic numerical processing has been regularly assessed using numerical
      nonsymbolic and symbolic comparison tasks. It has been assumed that these tasks
      index similar underlying processes. However, the evidence concerning the
      reliability and convergent validity across different versions of these tasks is
      inconclusive. We explored the reliability and convergent validity between two
      numerical comparison tasks (nonsymbolic vs. symbolic) in school-aged children.
      The relations between performance in both tasks and mental arithmetic were
      described and a developmental trajectories' analysis was also conducted. The
      influence of verbal and visuospatial working memory processes and age was
      controlled for in the analyses. Results show significant reliability (p < .001)
      between Block 1 and 2 for nonsymbolic task (global adjusted RT (adjRT): r = .78,
      global efficiency measures (EMs): r = .74) and, for symbolic task (adjRT: r =
      .86, EMs: r = .86). Also, significant convergent validity between tasks (p <
      .001) for both adjRT (r = .71) and EMs (r = .70) were found after controlling for
      working memory and age. Finally, it was found the relationship between
      nonsymbolic and symbolic efficiencies varies across the sample's age range.
      Overall, these findings suggest both tasks index the same underlying cognitive
      architecture and are appropriate to explore the Approximate Number System (ANS)
      characteristics. The evidence supports the central role of ANS in arithmetic
      efficiency and suggests there are differences across the age range assessed,
      concerning the extent to which efficiency in nonsymbolic and symbolic tasks
      reflects ANS acuity.

PMID- 29199627
TI  - Selectively Electron-Transparent Microstamping Toward Concurrent Digital Image
      Correlation and High-Angular Resolution Electron Backscatter Diffraction (EBSD)
      Analysis.
AB  - Digital image correlation (DIC) in a scanning electron microscope and high
      angular resolution electron backscatter diffraction (HREBSD) provide valuable and
      complementary data concerning local deformation at the microscale. However,
      standard surface preparation techniques are mutually exclusive, which makes
      combining these techniques in situ impossible. This paper introduces a new method
      of applying surface patterning for DIC, namely a urethane microstamp, that
      provides a pattern with enough contrast for DIC at low accelerating voltages, but
      is virtually transparent at the higher voltages necessary for HREBSD and
      conventional EBSD analysis. Furthermore, microstamping is inexpensive and
      repeatable, and is more suitable to the analysis of patterns from complex surface
      geometries and larger surface areas than other patterning techniques.

PMID- 29199628
TI  - Evaluation of food photographs assessing the dietary intake of children up to 10
      years old.
AB  - OBJECTIVE: Young children lack basic skills related to recognizing the types of
      foods they consume and dietary surveys often rely on parents' response. The
      present study aimed to evaluate how well parents of children aged from 3 months
      to 10 years perceive images of portions of foods commonly consumed by young
      children. DESIGN: Pre-weighed, actual food portions (n 2314) were shown to the
      study participants who were asked to indicate the picture that corresponded to
      the food in view. Mean differences between picture numbers selected and shown
      were estimated and compared using unpaired t tests or Tukey-Cramer pairwise
      comparisons. SETTING: Real-time testing of parents' perception of food images
      presenting portion sizes consumed by children up to 10 years old. SUBJECTS: A
      convenience sample of 138 parents/caregivers of young children (69 % females).
      RESULTS: Individuals selected the correct or adjacent image in about 97 % of the
      assessments. Images presenting amorphous solids (i.e. pies and pastries with a
      filling), liquid or semi-liquid dishes (i.e. soups, porridges, fruit and
      vegetable purees) were more prone to bias. There was no indication that personal
      characteristics (gender, age, educational background, age, number of offspring)
      were associated with differences in the way parents/caregivers perceived the food
      pictures. CONCLUSIONS: Food pictures may not be appropriate to quantify the
      intake of liquid, semi-liquid or amorphous solid foods in surveys addressing
      young children and studies evaluating their performance as food portion anchors
      should ensure the inclusion of several and various amorphous foods in the
      assessment.

PMID- 29199629
TI  - Exploring the association of urban or rural county status and environmental,
      nutrition- and lifestyle-related resources with the efficacy of SNAP-Ed
      (Supplemental Nutrition Assistance Program-Education) to improve food security.
AB  - OBJECTIVE: To investigate the association of policy, systems and environmental
      factors with improvement in household food security among low-income Indiana
      households with children after a Supplemental Nutrition Assistance Program
      Education (SNAP-Ed) direct nutrition education intervention. DESIGN: Household
      food security scores measured by the eighteen-item US Household Food Security
      Survey Module in a longitudinal randomized and controlled SNAP-Ed intervention
      study conducted from August 2013 to April 2015 were the response variable.
      Metrics to quantify environmental factors including classification of urban or
      rural county status; the number of SNAP-authorized stores, food pantries and
      recreational facilities; average fair market housing rental price; and natural
      amenity rank were collected from government websites and data sets covering the
      years 2012-2016 and used as covariates in mixed multiple linear regression
      modelling. SETTING: Thirty-seven Indiana counties, USA, 2012-2016. SUBJECTS: SNAP
      Ed eligible adults from households with children (n 328). RESULTS: None of the
      environmental factors investigated were significantly associated with changes in
      household food security in this exploratory study. CONCLUSIONS: SNAP-Ed improves
      food security regardless of urban or rural location or the environmental factors
      investigated. Expansion of SNAP-Ed in rural areas may support food access among
      the low-income population and reduce the prevalence of food insecurity in rural
      compared with urban areas. Further investigation into policy, systems and
      environmental factors of the Social Ecological Model are warranted to better
      understand their relationship with direct SNAP-Ed and their impact on diet
      related behaviours and food security.

PMID- 29199630
TI  - Adherence to self-monitoring healthy lifestyle behaviours through mobile phone
      based ecological momentary assessments and photographic food records over 6
      months in mostly ethnic minority mothers.
AB  - OBJECTIVE: Mobile phones can replace traditional self-monitoring tools through
      cell phone-based ecological momentary assessment (CEMA) of lifestyle behaviours
      and camera phone-based images of meals, i.e. photographic food records (PFR).
      Adherence to mobile self-monitoring needs to be evaluated in real-world treatment
      settings. Towards this goal, we examine CEMA and PFR adherence to the use of a
      mobile app designed to help mothers self-monitor lifestyle behaviours and stress.
      Design/Setting In 2012, forty-two mothers recorded CEMA of diet quality,
      exercise, sleep, stress and mood four times daily and PFR during meals over 6
      months in Los Angeles, California, USA. SUBJECTS: A purposive sample of mothers
      from mixed ethnicities. RESULTS: Adherence to recording CEMA at least once daily
      was higher compared with recording PFR at least once daily over the study period
      (74 v. 11 %); adherence to both types of reports decreased over time.
      Participants who recorded PFR for more than a day (n 31) were more likely to be
      obese v. normal- to overweight and to have higher blood pressure, on average (all
      P<0.05). Based on random-effects regression, CEMA and PFR adherence was highest
      during weekdays (both P<0.01). Additionally, PFR adherence was associated with
      older age (P=0.04). CEMA adherence was highest in the morning (P<0.01). PFR
      recordings occurred throughout the day. CONCLUSIONS: Variations in population and
      temporal characteristics should be considered for mobile assessment schedules.
      Neither CEMA nor PFR alone is ideal over extended periods.

PMID- 29199631
TI  - Aggressors and Victims in Bullying and Cyberbullying: A Study of Personality
      Profiles using the Five-Factor Model.
AB  - Bullying and cyberbullying are highly prevalent in today's society. However, the
      personality profiles of different roles involved in this phenomenon remain little
      known. This study aims (1) to examine the association between bullying and
      cyberbullying in adolescents; and (2) to analyze the relationship between
      bullying and cyberbullying in terms of the domains and facets of the five-factor
      model (FFM). A total of 910 adolescents aged 12 to 19 years old participated.
      They were administered self-report assessments of aggression and victimization in
      bullying and cyberbullying, as well as the JS-NEO-S questionnaire. The results
      provide evidence of co-occurrence between bullying and cyberbullying (p < .001).
      We observed higher neuroticism in victims and aggressor-victims, higher openness
      in victims, higher agreeableness in victims and non-aggressor non-victims and
      higher conscientiousness in non-aggressor non-victims as compared with the rest
      of the groups (p < .001). Comparison of the four cyberbullying groups showed that
      cybervictims score higher in neuroticism and openness, cybervictims and non
      cybervictims non-cyberaggressors score higher in agreeableness and non
      cybervictims non-cyberaggressors score higher in conscientiousness (p < .001) In
      conclusion, this study provides a broad, systematic view of the personality
      traits associated with different roles implicated in traditional bullying and
      cyberbullying.

PMID- 29199632
TI  - Nucleation and Growth of Mg-Calcite Spherulites Induced by the Bacterium
      Curvibacter lanceolatus Strain HJ-1.
AB  - Calcite spherulites have been observed in many laboratory experiments with
      different bacteria, and spherulitic growth has received much interest in
      mineralogy research. However, the nucleation and growth mechanism, as well as
      geological significance of calcite spherulites in solution with bacteria is still
      unclear. Herein, spherulites composed of an amorphous core, a Mg-calcite body and
      an organic film were precipitated by the Curvibacter lanceolatus HJ-1 bacterial
      strain in a solution with a molar Mg/Ca ratio of 3. Based on the results, we
      provide a possible mechanism for the biomineralization of Mg-calcite spherulites.
      First, amorphous calcium carbonate particles are deposited and aggregated into a
      stable sphere-like core in combination with organic molecules. The core then acts
      as the nucleus of spherulitic radial growth. Finally, the organic film grows on
      the surface of Mg-calcite spherulites as a result of bacterial metabolism and
      calcification. These findings provide insight into the growth mode and
      crystallization of biogenic spherulites during biomineralization, and are of
      significance in the application of novel biological materials.

PMID- 29199633
TI  - Current nut recommendation practices differ between health professionals in New
      Zealand.
AB  - OBJECTIVE: Despite evidence linking regular nut consumption with reduced chronic
      disease risk, population-level intakes remain low. Research suggests nut
      promoting advice from doctors facilitates regular nut consumption. However, there
      is no information on current nut recommendation practices of health
      professionals. The aim of the present study was to examine the advice provided by
      health professionals regarding nut consumption. DESIGN: In this cross-sectional
      study, participants were invited to complete a survey including questions about
      their nut recommendation practices. SETTING: New Zealand (NZ). SUBJECTS: The NZ
      Electoral Roll was used to identify dietitians, general practitioners and
      practice nurses. RESULTS: In total 318 dietitians, 292 general practitioners and
      149 practice nurses responded. Dietitians were more likely (82.7 %) to recommend
      patients increase consumption of nuts than general practitioners (55.5 %) and
      practice nurses (63.1 %; both P<0.001). The most popular nuts recommended were
      almonds, Brazil nuts and walnuts, with most health professionals recommending raw
      nuts. The most common recommendation for frequency of consumption by dietitians
      and practice nurses was to eat nuts every day, while general practitioners most
      frequently recommended 2-4 times weekly, although not statistically significantly
      different between professions. Dietitians recommended a significantly greater
      amount of nuts (median 30 g/d) than both general practitioners and practice
      nurses (20 g/d; both P<0.001). CONCLUSIONS: Dietitians were most likely to
      recommend consumption of nuts in accordance with current guidelines, but there
      are opportunities to improve the adoption of nut consumption recommendations for
      all professions. This may be a viable strategy for increasing population-level
      nut intakes to reduce chronic disease.

PMID- 29199634
TI  - Optimism and quality of life in patients with heart failure.
AB  - OBJECTIVES: Health-related quality of life (HR-QoL) of patients with heart
      failure (HF) is low despite the aim of HF treatment to improve HR-QoL. To date,
      most studies have focused on medical and physical factors in relation to HR-QoL,
      few data are available on the role of emotional factors such as dispositional
      optimism. This study examines the prevalence of optimism and pessimism in HF
      patients and investigates how optimism and pessimism are associated with
      different patient characteristics and HR-QoL. METHODS: Dispositional optimism was
      assessed in 86 HF patients (mean age 70 +/- 9 years, 28% female, mean left
      ventricular ejection fraction 33%) with the Revised Life Orientation Test (LOT
      R). HR-QoL was assessed with the Minnesota Living with Heart Failure
      Questionnaire and the EuroQol. RESULTS: The (mean +/- SD) total score on the LOT
      R was 14.6 +/- 2.9 (theoretical range 0-24) and the scores on the subscales
      optimism and pessimism were 8.1 +/- 1.9 and 5.5 +/- 2.5, respectively. Higher age
      was related to more optimism (r = 0.22, p < 0.05), and optimism was associated
      with higher generic HR-QoL (B = 0.04, p < 0.05). Significance of results The
      association found between optimism and generic HR-QoL of HF patients can lead to
      promising strategies to improve HF patients' HR-QoL, particularly because the
      literature has indicated that optimism is a modifiable condition.

PMID- 29199635
TI  - Melatonin Elicits Stimulatory Action on the Adrenal Gland of Soay Ram:
      Morphometrical, Immunohistochemical, and Ultrastructural Study.
AB  - Endogenous melatonin is a hormone secreted by pineal gland; it has several roles
      in metabolism, reproduction, and remarkable antioxidant properties. Studies on
      the melatonin effect on the adrenal glands which are important endocrine organs,
      controlling essential physiological functions, are still deficient. In this
      study, we attempted to investigate the effect of exogenous melatonin treatment on
      the adrenal cortex and medulla using several approaches. Adrenal glands of 15
      Soay ram were examined to detect the effect of melatonin treatment. Our results
      revealed that the cells of adrenal cortex of the treated animals were separated
      by wide and numerous blood sinusoids and showed signs of increase steroidogenic
      activity, which are evidenced by functional hypertrophy with increase profiles of
      mitochondria, smooth endoplasmic reticulum, and lipid droplets. The most striking
      ultrastructural features in the medulla of the treated group were the engorgement
      of chromaffin cells with enlarged secretory granules enclosed within a
      significantly increased diameter of these cells. The cytoplasm of these cells
      showed numerous mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus,
      lysosomes, and glycogen granules. Exocytosis of secretory granules to the lumen
      of blood vessels was evident in the treated group. Piecemeal degranulation mode
      of secretion was recorded after melatonin treatment. Chromaffin cells in the
      control group expressed moderate immunoreactivity to Synaptophysin and tyrosine
      hydroxylase, compared with intensified expression after melatonin treatment. The
      ganglion cells of the melatonin-treated group showed a significant increase in
      diameter with numerous rER. The most interesting feature in this study is the
      presence of small granule chromaffin cells (SGC) and telocytes (TCs) for the
      first time in the adrenal glands of sheep. Moreover, these SGC cells, Schwann
      cells, fibroblasts, and progenitor stem cells showed a stimulatory response. The
      TCs were small branched cells scattered in the adrenal glands around cortical
      cells, chromaffin cells, nerve fibers, and blood vessels. These cells increased
      significantly in number, length of their telopodes, and secretory activity after
      melatonin treatment. In addition, multiple profiles of unmyelinated nerve fibers
      were demonstrated in all treated specimens. These results indicated that
      melatonin treatment caused a stimulatory action on all cellular and neuronal
      elements of the adrenal gland. This study may act as a new direction for
      treatment of adrenal insufficiency.

PMID- 29199636
TI  - Identifying ADHD children using hemodynamic responses during a working memory
      task measured by functional near-infrared spectroscopy.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a
      neurodevelopmental disorder affecting children and adults. Previous studies found
      that functional near-infrared spectroscopy (fNIRS) can reveal significant group
      differences in several brain regions between ADHD children and healthy controls
      during working memory tasks. This study aimed to use fNIRS activation patterns to
      identify ADHD children from healthy controls. APPROACH: FNIRS signals from 25
      ADHD children and 25 healthy controls performing the n-back task were recorded;
      then, multivariate pattern analysis was used to discriminate ADHD individuals
      from healthy controls, and classification performance was evaluated for
      significance by the permutation test. MAIN RESULTS: The results showed that 86.0%
      ([Formula: see text]) of participants can be correctly classified in leave-one
      out cross-validation. The most discriminative brain regions included the
      bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex,
      right posterior prefrontal cortex, and right temporal cortex. SIGNIFICANCE: This
      study demonstrated that, in a small sample, multivariate pattern analysis can
      effectively identify ADHD children from healthy controls based on fNIRS signals,
      which argues for the potential utility of fNIRS in future assessments.

PMID- 29199637
TI  - Automated 3D bioassembly of micro-tissues for biofabrication of hybrid tissue
      engineered constructs.
AB  - Bottom-up biofabrication approaches combining micro-tissue fabrication techniques
      with extrusion-based 3D printing of thermoplastic polymer scaffolds are emerging
      strategies in tissue engineering. These biofabrication strategies support native
      self-assembly mechanisms observed in developmental stages of tissue or organoid
      growth as well as promoting cell-cell interactions and cell differentiation
      capacity. Few technologies have been developed to automate the precise assembly
      of micro-tissues or tissue modules into structural scaffolds. We describe an
      automated 3D bioassembly platform capable of fabricating simple hybrid constructs
      via a two-step bottom-up bioassembly strategy, as well as complex hybrid
      hierarchical constructs via a multistep bottom-up bioassembly strategy. The
      bioassembly system consisted of a fluidic-based singularisation and injection
      module incorporated into a commercial 3D bioprinter. The singularisation module
      delivers individual micro-tissues to an injection module, for insertion into
      precise locations within a 3D plotted scaffold. To demonstrate applicability for
      cartilage tissue engineering, human chondrocytes were isolated and micro-tissues
      of 1 mm diameter were generated utilising a high throughput 96-well plate format.
      Micro-tissues were singularised with an efficiency of 96.0 +/- 5.1%. There was no
      significant difference in size, shape or viability of micro-tissues before and
      after automated singularisation and injection. A layer-by-layer approach or
      aforementioned bottom-up bioassembly strategy was employed to fabricate a
      bilayered construct by alternatively 3D plotting a thermoplastic (PEGT/PBT)
      polymer scaffold and inserting pre-differentiated chondrogenic micro-tissues or
      cell-laden gelatin-based (GelMA) hydrogel micro-spheres, both formed via high
      throughput fabrication techniques. No significant difference in viability between
      the construct assembled utilising the automated bioassembly system and manually
      assembled construct was observed. Bioassembly of pre-differentiated micro-tissues
      as well as chondrocyte-laden hydrogel micro-spheres demonstrated the flexibility
      of the platform while supporting tissue fusion, long-term cell viability, and
      deposition of cartilage-specific extracellular matrix proteins. This technology
      provides an automated and scalable pathway for bioassembly of both simple and
      complex 3D tissue constructs of clinically relevant shape and size, with
      demonstrated capability to facilitate direct spatial organisation and
      hierarchical 3D assembly of micro-tissue modules, ranging from biomaterial free
      cell pellets to cell-laden hydrogel formulations.

PMID- 29199639
TI  - The ovarian cycle may influence the exhaled volatile organic compound profile
      analyzed by an electronic nose.
AB  - INTRODUCTION: We aimed to investigate whether the sex hormone profile during the
      ovarian cycle in healthy women could affect the volatile organic compound (VOC)
      profile analyzed by an electronic nose (e-nose). METHODS: We enrolled 21 healthy,
      never-smoking, regularly menstruating women who were not taking any medications.
      A series of exhaled breath measurements were performed on all subjects at
      predefined intervals (days 1-6, 7-12, 13-19, 20-25 and 26-31; day 1 was the first
      day of menstruation) during their ovarian cycle and analyzed by an e-nose
      (Cyranose 320). RESULTS: By principal component analysis, significant
      modifications of the exhaled VOC profile were observed over the cycle for
      principal component 1 (PC1; p = 0.001). In particular, the PC1 value was
      significantly higher during the premenstrual period and during menstruation
      compared with the first third of estrogen phase, mid-cycle and the first third of
      progestational phase (for all parameters p < 0.05 and p < 0.01, respectively).
      Subsequent linear discriminant analysis confirmed the above findings.
      CONCLUSIONS: The ovarian cycle may alter the exhaled VOC pattern and this should
      be taken into account during serial measurements of these markers in the female
      population.

PMID- 29199638
TI  - Volatile fingerprinting of human respiratory viruses from cell culture.
AB  - Volatile metabolites are currently under investigation as potential biomarkers
      for the detection and identification of pathogenic microorganisms, including
      bacteria, fungi, and viruses. Unlike bacteria and fungi, which produce distinct
      volatile metabolic signatures associated with innate differences in both primary
      and secondary metabolic processes, viruses are wholly reliant on the metabolic
      machinery of infected cells for replication and propagation. In the present
      study, the ability of volatile metabolites to discriminate between respiratory
      cells infected and uninfected with virus, in vitro, was investigated. Two
      important respiratory viruses, namely respiratory syncytial virus (RSV) and
      influenza A virus (IAV), were evaluated. Data were analyzed using three different
      machine learning algorithms (random forest (RF), linear support vector machines
      (linear SVM), and partial least squares-discriminant analysis (PLS-DA)), with
      volatile metabolites identified from a training set used to predict sample
      classifications in a validation set. The discriminatory performances of RF,
      linear SVM, and PLS-DA were comparable for the comparison of IAV-infected versus
      uninfected cells, with area under the receiver operating characteristic curves
      (AUROCs) between 0.78 and 0.82, while RF and linear SVM demonstrated superior
      performance in the classification of RSV-infected versus uninfected cells (AUROCs
      between 0.80 and 0.84) relative to PLS-DA (0.61). A subset of discriminatory
      features were assigned putative compound identifications, with an overabundance
      of hydrocarbons observed in both RSV- and IAV-infected cell cultures relative to
      uninfected controls. This finding is consistent with increased oxidative stress,
      a process associated with viral infection of respiratory cells.

PMID- 29199640
TI  - Effects of humidity, CO2 and O2 on real-time quantitation of breath biomarkers by
      means of PTR-ToF-MS.
AB  - Proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) represents
      an attractive tool for the real-time analysis of VOC profiles in human breath.
      Quantification of breath VOCs by means of direct MS may be affected by the
      matrix, as human breath not only contains several hundred VOCs at the ppbV-pptV
      level, but is water saturated and contains percentage levels of CO2.
      Investigation of breath biomarkers in clinical studies requires quantitative and
      comparable results. We therefore systematically assessed the effect of humidity,
      CO2 and O2 on the results of PTR-MS analysis. We investigated more than 20 VOCs,
      including aldehydes, ketones, aromatic compounds and hydrocarbons with different
      sample humidity, CO2 and O2 content. The influence of data processing (e.g.
      normalization to the H3O+ ion count) was also addressed. An increase of the H3O+
      count of about 20% was observed when the humidity in the sample was increased to
      breath levels. Large differences regarding the measured VOC intensities were
      found between the dry and humid samples. Data normalization to the H3O+ or water
      clusters could not fully compensate for the humidity-dependent effects. However,
      as the determination of most VOCs linearly depends on the humidity over the whole
      investigated range, factor-based correction seems possible. The effects of CO2
      were more pronounced in the dry samples than in the humid samples but only had a
      minor influence on the results. The same was true for the influence of O2. For
      the reliable quantification of VOCs in clinical studies and for the
      standardization of VOC research, well-adapted calibration standards are required
      for PTR-MS analysis.

PMID- 29199641
TI  - Controllable nanoscale inverted pyramids for highly efficient quasi
      omnidirectional crystalline silicon solar cells.
AB  - Nanoscale inverted pyramid structures (NIPs) have always been regarded as one of
      the paramount light management schemes to achieve extraordinary performance in
      various devices, especially in solar cells, due to their outstanding
      antireflection ability with relative lower surface enhancement ratio. However,
      current approaches to fabricating NIPs are complicated and not cost-effective for
      massive cell production in the photovoltaic industry. Here, controllable NIPs are
      fabricated on crystalline silicon (c-Si) wafers by Ag-catalyzed chemical etching
      and alkaline modification, which is a preferable all-solution-processed method.
      Through applying the NIPs to c-Si solar cells and optimizing the cell design, we
      have successfully achieved highly efficient textured solar cells with NIPs of a
      champion efficiency of 20.5%. Significantly, these NIPs are further demonstrated
      to possess a quasi-omnidirectional property over broad sunlight incident angles
      of approximately 0 degrees -60 degrees . Moreover, NIPs are theoretically
      revealed to offer light trapping advantages for ultrathin c-Si solar cells.
      Hence, NIPs formed by a controllable method exhibit great potential to be used in
      the future photovoltaic industry as surface texture.

PMID- 29199642
TI  - Signal processing methods for reducing artifacts in microelectrode brain
      recordings caused by functional electrical stimulation.
AB  - OBJECTIVE: Functional electrical stimulation (FES) is a promising technology for
      restoring movement to paralyzed limbs. Intracortical brain-computer interfaces
      (iBCIs) have enabled intuitive control over virtual and robotic movements, and
      more recently over upper extremity FES neuroprostheses. However, electrical
      stimulation of muscles creates artifacts in intracortical microelectrode
      recordings that could degrade iBCI performance. Here, we investigate methods for
      reducing the cortically recorded artifacts that result from peripheral electrical
      stimulation. APPROACH: One participant in the BrainGate2 pilot clinical trial had
      two intracortical microelectrode arrays placed in the motor cortex, and thirty
      six stimulating intramuscular electrodes placed in the muscles of the
      contralateral limb. We characterized intracortically recorded electrical
      artifacts during both intramuscular and surface stimulation. We compared the
      performance of three artifact reduction methods: blanking, common average
      reference (CAR) and linear regression reference (LRR), which creates channel
      specific reference signals, composed of weighted sums of other channels. MAIN
      RESULTS: Electrical artifacts resulting from surface stimulation were 175  * 
      larger than baseline neural recordings (which were 110 uV peak-to-peak), while
      intramuscular stimulation artifacts were only 4  *  larger. The artifact
      waveforms were highly consistent across electrodes within each array. Application
      of LRR reduced artifact magnitudes to less than 10 uV and largely preserved the
      original neural feature values used for decoding. Unmitigated stimulation
      artifacts decreased iBCI decoding performance, but performance was almost
      completely recovered using LRR, which outperformed CAR and blanking and extracted
      useful neural information during stimulation artifact periods. SIGNIFICANCE: The
      LRR method was effective at reducing electrical artifacts resulting from both
      intramuscular and surface FES, and almost completely restored iBCI decoding
      performance (>90% recovery for surface stimulation and full recovery for
      intramuscular stimulation). The results demonstrate that FES-induced artifacts
      can be easily mitigated in FES  +  iBCI systems by using LRR for artifact
      reduction, and suggest that the LRR method may also be useful in other noise
      reduction applications.

PMID- 29199643
TI  - Thermometry properties of Er, Yb-Gd2O2S microparticles: dependence on the
      excitation mode (cw versus pulsed excitation) and excitation wavelength (980 nm
      versus 1500 nm).
AB  - Herein, we present a first report on the luminescence thermometry properties of
      Er, Yb doped Gd2O2S microparticles under near infrared up-conversion excitation
      at 980 and 1500 nm measured in the 280-800 K interval. The thermometry properties
      are assessed using both cw and ns pulsed excitation as well as tuning the
      excitation wavelength across Yb and Er absorption profiles. For low cw (300 mW cm
      1) and pulsed ns (400 / 550 mW cm-1) excitation modes, no thermal load is
      observed. At room-temperature (280 K), the maximum relative sensitivity values
      are comparable under pulsed excitation at 980 and 1500 nm, around ~0.01 and
      ~0.008% K-1, respectively. In addition, a relative intense up-conversion emission
      at 980 nm under excitation at 1500 nm is measured. Our findings evidence
      attractive up-conversion and thermometry properties Er, Yb doped Gd2O2S under
      near-infrared excitation and highlight the need to explore further these
      properties in the nanoparticulate regime.

PMID- 29199644
TI  - A facile approach for reducing the working voltage of Au/TiO2/Au nanostructured
      memristors by enhancing the local electric field.
AB  - Memristor devices have attracted tremendous interest due to different
      applications ranging from nonvolatile data storage to neuromorphic computing
      units. Exploring the role of surface roughness of the bottom electrode
      (BE)/active layer interface provides useful guidelines for the optimization of
      the memristor switching performance. This study focuses on the effect of surface
      roughness of the BE electrode on the switching characteristics of Au/TiO2/Au
      three-layer memristor devices. An optimized wet-etching treatment condition was
      found to modify the surface roughness of the Au BE where the measurement results
      indicate that the roughness of the Au BE is affected by both duration time and
      solution concentrations of the wet-etching process. Then we fabricated arrays of
      TiO2-based nanostructured memristors sandwiched between two sets of cross-bar Au
      electrode lines (junction area 900 MUm2). The results revealed a reduction in the
      working voltages in current-voltage characteristic of the device performance when
      increasing the surface roughness at the Au(BE)/TiO2 active layer interface. The
      set voltage of the device (Vset) significantly decreased from 2.26-1.93 V when we
      increased the interface roughness from 4.2-13.1 nm. The present work provides
      information for better understanding the switching mechanism of titanium-dioxide
      based devices, and it can be inferred that enhancing the roughness of the Au
      BE/TiO2 active layer interface leads to a localized non-uniform electric field
      distribution that plays a vital role in reducing the energy consumption of the
      device.

PMID- 29199645
TI  - Epigenetic Drug Repositioning for Alzheimer's Disease Based on Epigenetic Targets
      in Human Interactome.
AB  - BACKGROUND: Epigenetics has emerged as an important field in drug discovery.
      Alzheimer's disease (AD), the leading neurodegenerative disorder throughout the
      world, is shown to have an epigenetic basis. Currently, there are very few
      effective epigenetic drugs available for AD. OBJECTIVE: In this work, for the
      first time we have proposed 14 AD repositioning epigenetic drugs and identified
      their targets from extensive human interactome. METHODS: Interacting partners of
      the AD epigenetic proteins were identified from the extensive human interactome
      to construct Epigenetic Protein-Protein Interaction Network (EP-PPIN). Epigenetic
      Drug-Target Network (EP-DTN) was constructed with the drugs associated with the
      proteins of EP-PPIN. Regulation of non-coding RNAs associated with the target
      proteins of these drugs was also studied. AD related target proteins, epigenetic
      targets, enriched pathways, and functional categories of the proposed
      repositioning drugs were also studied. RESULTS: The proposed 14 AD epigenetic
      repositioning drugs have overlapping targets and miRs with known AD epigenetic
      targets and miRs. Furthermore, several shared functional categories and enriched
      pathways were obtained for these drugs with FDA approved epigenetic drugs and
      known AD drugs. CONCLUSIONS: The findings of our work might provide insight into
      future AD epigenetic-therapeutics.

PMID- 29199646
TI  - Recent Progress in Alzheimer's Disease Research, Part 2: Genetics and
      Epidemiology.

PMID- 29199648
TI  - Proteomic investigation of resistance to chemotherapy drugs in osteosarcoma.
AB  - BACKGROUND: Osteosarcoma, which is also termed osteogenic sarcoma or osteoma
      sarcomatosum, is the most common form of bone cancer. Typical osteosarcoma can
      occur at any age, including in infants, children, and the elderly, but more than
      half of cases occur in individuals who are 10-20 years old. OBJECTIVE: Here, the
      objective was to search for protein markers to indicate resistance to cisplatin
      in osteosarcoma and provide a theoretical basis for the early and accurate use of
      cisplatin to treat osteosarcoma. METHODS: Thirty patients with osteosarcoma were
      selected for the study. Experimental studies on the chemosensitivity of
      osteosarcoma using an in vitro kit method were performed, and cisplatin-resistant
      and cisplatin-sensitive osteosarcoma tissues were obtained. A representative
      sample was chosen to analyze and identify differentially expressed proteins in
      cisplatin-resistant tissues. RESULTS: The osteosarcoma-sensitive tissue was
      analyzed using 2-D electrophoresis and time-of-flight mass spectrometry.
      Differently expressed proteins were analyzed by western blotting to identify
      markers. Cisplatin-resistant and cisplatin-sensitive osteosarcoma tissues were
      obtained. Five significantly differentially expressed proteins were identified,
      including ALDOA and PGK1. CONCLUSIONS: The results indicate that ALDOA and PGK1
      might be appropriate markers that can be used when treating osteosarcoma with
      cisplatin.

PMID- 29199649
TI  - Testosterone and its metabolites: differential associations with cardiovascular
      and cerebrovascular events in men.
AB  - As men grow older, circulating testosterone declines while the incidence of
      cardiovascular disease increases. Thus, the role of sex hormones as biomarkers,
      and possibly contributing factors to clinical manifestations of cardiovascular
      disease in the increasing demographic of aging men, has attracted considerable
      interest. This review focuses on observational studies of endogenous androgens,
      namely circulating testosterone and dihydrotestosterone, which have examined
      their associations with cardiovascular events such as myocardial infarction and
      stroke. Studies which have examined the associations of endogenous estrogens,
      namely circulating estradiol, with these outcomes are also discussed. In large
      prospective cohort studies of predominantly middle-aged and older men, lower
      circulating testosterone consistently predicts higher incidence of cardiovascular
      events. Of note, both lower circulating testosterone and lower
      dihydrotestosterone are associated with higher incidence of stroke. These
      associations are less apparent when myocardial infarction is considered as the
      outcome. Results for estradiol are inconsistent. Lower circulating testosterone
      has been shown to predict higher cardiovascular disease-related mortality, as has
      lower circulating dihydrotestosterone. It is possible that the relationship of
      circulating androgens to cardiovascular events or mortality outcomes may be U
      shaped rather than linear, with an optimal range defining men at lowest risk.
      Epidemiological studies are observational in nature and do not prove causality.
      Associations observed in studies of endogenous androgens need not necessarily
      translate into similar effects of exogenous androgens. Rigorous randomized
      controlled trials are needed to clarify the effects of testosterone treatment on
      cardiovascular risk in men.

PMID- 29199650
TI  - Tuberculosis in epidermal growth factor receptor mutation in lung adenocarcinoma
      on treatment with gefitinib/erlotinib.

PMID- 29199651
TI  - Is pulmonary metastasectomy beneficial in head and neck squamous cell carcinoma?
      A review of literature.
AB  - Metastatic head and neck squamous cell carcinoma (HNSCC) has traditionally
      carried a dismal prognosis; however with advances in care, it has been shown that
      pulmonary metastasectomy is a viable therapeutic option in selected patients,
      palliating symptoms and improving survival. With the increasing incidence of
      human papilloma virus-related HNSCC and better availability of minimal access
      surgery, there is a need to better understand the role of pulmonary
      metastasectomy in the treatment of HNSCC. This article summarizes the literature
      on indications, results, surgical options and approaches, clinical dilemmas, and
      controversies associated with pulmonary metastasectomy in HNSCC, to identify
      suitable candidates and optimize outcomes.

PMID- 29199652
TI  - Comparison of conventional fractionation (five fractions per week) and altered
      fractionation (six fractions per week) in stage I and II squamous cell carcinoma
      of oropharynx: An institutional study.
AB  - BACKGROUND: The radiotherapy (RT) dose and fractionation schedule for head and
      neck cancers for locoregional control and acceptable organ toxicity are still
      debatable. Accelerated RT includes administration of six fractions per week with
      the same dose per fraction. AIM: Comparison of conventional versus accelerated RT
      in terms of locoregional control, and acute and late radiation toxicity in
      squamous cell carcinoma oropharynx (stage I and II). SETTINGS AND DESIGN:
      Prospective, double arm, phase 2, randomized study. MATERIALS AND METHODS: Sixty
      patients of squamous cell carcinoma oropharynx (stage I and II) were randomized
      in two arms (accelerated fractionation, arm 1 and conventional fractionation, arm
      2). All patients received RT dose of 66 Gray (Gy) in 33 fractions (#). The
      patients in arm 1 received six fractions per week with 2 Gy/# (Monday-Saturday)
      and in arm 2, five fractions per week with 2 Gy/# (Monday-Friday). No
      chemotherapy was administered. During and after the treatment, locoregional
      control, and acute and late radiation toxicity were assessed. RESULTS: At 1-year
      follow-up, 76% patients in arm 1 and 64% patients in arm 2 had complete response.
      The recurrence rate at the end of 1 year in arm 1 was 12% and it was 20% in arm
      2.The acute Grade 2 and 3 toxicities were higher in the accelerated arm and no
      significant difference in late toxicities was found. SPSS version 4.0 was used
      for statistical analysis. CONCLUSION: Accelerated fractionation provides better
      locoregional control with higher but acceptable acute and equal late radiation
      toxicity in squamous cell carcinoma oropharynx.

PMID- 29199653
TI  - Oral health-related quality of life in patients treated for oral malignancy at
      Kanchipuram district, India: A cross-sectional study.
AB  - BACKGROUND: The modern-day onco-surgical therapy is now concerned on the overall
      Quality of Life after treatment of the patient. There is need to evaluate final
      outcome following the different combination of treatment modalities available to
      make better therapeutic treatment decisions. AIM: The aim of this study was to
      assess Oral health related quality of life (OHRQoL) in patients with oral
      malignancies who had undergone various treatments. SETTINGS AND DESIGN: A Cross
      sectional study was conducted among 90 patients between October 2016 to January
      2017 in private hospitals, kanchipuram, India. MATERIALS AND METHODS:
      Participants were grouped based on the treatment they had undergone into Group I 
      Surgery alone, Group II - Surgery and Radiotherapy, Group III- Surgery,
      chemotherapy and radiotherapy and assessed for OHRQoL using the shorter version
      of Oral health impact profile -14 (OHIP-14) questionnaire. STATISTICAL ANALYSIS:
      Descriptive analysis of socio demographic variables and OHIP 14 was performed
      using Chi-square test and one way ANOVA. RESULTS: Among the 90 participants,
      43.3% belonged to upper lower class and 38.3% to lower class. Buccal mucosa
      (58.9%) was found to be the most frequent site. Among the clinical staging, Stage
      II (33.33%) oral cancer was more prevalent. No statistically significant
      differences in the OHIP mean score for Groups, I, II, III. Among the domains
      functional limitation was significantly different in the three groups.
      CONCLUSION: Patients with oral malignancies who had been treated surgically alone
      had better Quality of life when compared to the combined treatment modalities.

PMID- 29199654
TI  - Impact of induction chemotherapy to concurrent chemoirradiation over radiotherapy
      alone in advanced oral cavity.
AB  - BACKGROUND: Oral and oropharyngeal carcinomas representing about 90% of all oral
      malignancies are the sixth most common cancers worldwide. Basic modalities of
      cancer treatment are surgery, radiotherapy, and chemotherapy (CT) either alone or
      in combination. For squamous cell carcinoma (SCC) patients, induction CT followed
      by radiotherapy and concurrent CT are effective methods for improving response
      rates. MATERIALS AND METHODS: Fifty patients with advance stage oral cavity
      cancer with performance status >60% on Karnofsky performance scale and having no
      prior exposure to CT, radiotherapy, and surgery were included in the study. CT
      including bleomycin, methotrexate, and cisplatin was given on day 1 and repeated
      at an interval of 21 days. After the completion of three cycles, two groups (n =
      25 each) were formed. One group was treated with radiotherapy alone and other
      group of patients treated with radiotherapy and concurrent cisplatin infusion.
      The patient toxicities and response were evaluated. RESULTS: After completion of
      induction CT, both the groups responded with almost similar result. Nausea,
      vomiting, mucositis, and skin reactions during radiotherapy were observed in both
      groups but comparatively higher in Group "B." In Group B, 84% (vs. 60% in Group
      A) of patients showed complete response (CR) after completion of treatment, and
      out of 13 patients who responded partially to induction CT, 9 patients showed CR
      after concurrent chemoradiotherapy. CONCLUSION: This study showed the superiority
      of induction followed by concurrent chemoradiotherapy over induction plus
      radiotherapy alone in the treatment of advanced oral cavity neck SCC.

PMID- 29199655
TI  - Comparison of paclitaxel-cetuximab chemotherapy versus metronomic chemotherapy
      consisting of methotrexate and celecoxib as palliative chemotherapy in head and
      neck cancers.
AB  - BACKGROUND: The present match pair analysis was planned to compare the efficacy
      of cetuximab-paclitaxel-based chemotherapy versus metronomic therapy. MATERIALS
      AND METHODS: Sixty patients with metastatic/recurrent head and neck squamous cell
      cancer treated with weekly paclitaxel (80 mg/m2) and cetuximab were matched with
      sixty patients treated with oral metronomic chemotherapy consisting of
      methotrexate and celecoxib. The progression-free survival (PFS) and overall
      survival (OS) between the cohorts were compared using log-rank test. Cox
      proportional regression model was used to identify independent factors affecting
      PFS and OS. RESULTS: The median OS was 191 days (95% confidence interval [CI]:
      122.2-259.8 days) in metronomic cohort and 256 days (95% CI 177.0-334.9 days) in
      cetuximab cohort (hazard ratio: 0.58, 95% CI: 0.35-0.95, P = 0.031). On Cox
      proportional hazard model, Eastern Cooperative Oncology Group Performance Status
      (0-1 vs. 2) and therapy (cetuximab versus metronomic) had a statistically
      significant impact on OS. CONCLUSION: Cetuximab-based chemotherapy leads to a
      significant improvement in OS in the match pair analysis in comparison to
      metronomic chemotherapy.

PMID- 29199656
TI  - Retrospective analysis of palliative metronomic chemotherapy in head and neck
      cancer.
AB  - BACKGROUND: Metronomic chemotherapy has shown promising results in selected
      patients of head and neck cancer in a small randomized study. This retrospective
      analysis was done to see whether the efficacy of metronomic chemotherapy in an
      unselected cohort of head and neck cancer patients is similar to that reported in
      the randomized study and the influence of the site and subsite of head and neck
      cancer on survival. MATERIALS AND METHODS: This was a retrospective analysis of
      head and neck cancer patients who received palliative metronomic chemotherapy
      between January 2013 and February 2015. The data of these patients were collected
      from our palliative chemotherapy database maintained in medical oncology
      outpatient department. The overall survival (OS) was calculated in days from the
      date of start of chemotherapy to the date of death. Patients who had not expired
      at last follow-up were censored during estimation of OS by Kaplan-Meier method.
      Factors affecting OS were identified by COX regression analysis. RESULTS: Over
      the stipulated time period, 340 patients received palliative metronomic
      chemotherapy. The median age of these patients was 48 years (22-90 years). The
      sites of tumor origin were oral cavity in 281 patients (82.6%), oropharynx in 33
      patients (9.7%), larynx in seven patients (2.1%), hypopharynx in 12 patients
      (3.5%), and maxilla in seven patients (2.1%). Previous treatment was received by
      286 patients (84.1%). The median time to failure was 3.5 months (interquartile
      range 2.0-6.0 months). The overall median survival was 155 days (95% confidence
      interval 140.2-169.8 days). Failure within 6 months of previous treatment was the
      most important factor influencing OS. There was a trend toward lower OS in
      patients with oral cancers (139 days vs. 210 days). Among the various oral cancer
      subsites, oral tongue primary had a lower OS. CONCLUSION: Oral metronomic
      chemotherapy has promising results when used in a selected cohort of patients but
      has dismal results in patients who failed within 6 months of previous treatment.

PMID- 29199657
TI  - Sister Mary Joseph's nodule: Two rare cases of inoperable gallbladder cancer.

PMID- 29199658
TI  - An audit and analysis of different causes of defaults in patients receiving
      radiation for head and neck cancers: A tertiary regional cancer center
      experience.
AB  - CONTEXT: Strict adherence and timely completion of the external beam radiation
      therapy (EBRT) schedule is an important prognostic factor in the survival of head
      and neck cancer patients. However, many patients are unable to complete the
      radiation treatment due to various reasons resulting in a poor outcome. AIMS:
      This study aims to study the pattern and various possible causes of defaults for
      possible intervention. SETTINGS AND DESIGN: A retrospective epidemiological
      analysis. SUBJECTS AND METHODS: Patients receiving EBRT for head and neck cancers
      with curative intent from January 2015 to December 2015 but did not complete the
      prescribed treatment were included. Unplanned treatment breaks in the treatment
      was not taken into consideration. STATISTICAL ANALYSIS USED: SPSS version 21.
      RESULTS: Out of 458, 92 (20.08%) patients did not complete the EBRT (P = 0.06).
      Fifty-six out of total 92 patients (60.9%) who defaulted stopped taking treatment
      within halfway of the treatment (15 fraction) and 12 out of total 92 patients
      (13%) just at the 22nd/23rd fraction. Defaulter rates in patients from different
      places are in the range of 12.8% to 33.0% but was statistically not significant
      (P = 0.224). There was no particular age (P = 0.966), disease site (P = 0.354)
      preponderance among defaulters. Use of concurrent chemo-radiation in radical or
      adjuvant settings was also not related to defaults (P = 0.406). CONCLUSIONS:
      Radiation-induced acute toxicity, socioeconomic status and distance plays minimal
      role as a cause of patients who stop taking EBRT. There is no particular relation
      between age, disease site, treatment received before radiotherapy, intent of
      treatment, and concurrent chemoradiation-induced acute reactions with defaults
      among patients. Loss of income and work in the poor population during the
      treatment may be an important possible cause of defaults.

PMID- 29199659
TI  - Induction chemotherapy in locally advanced T4b oral cavity squamous cell cancers:
      A regional cancer center experience.
AB  - OBJECTIVES: The present study aimed to investigate the efficacy, toxicity, and
      impact of induction chemotherapy (IC) in locally advanced T4b oral cavity
      squamous cell cancers (OSCCs). MATERIALS AND METHODS: Patients diagnosed with
      locally advanced T4b OSCC from January 2013 to October 2016 at our center, who
      received 2-3 cycles of IC and then assessed for resectability, were reviewed
      retrospectively. Patients' profile, response, and toxicity of IC, resectability
      status, and overall survival (OS) were evaluated. Statistical analyses were
      performed by SPSS software version 17. RESULTS: A total of 116 patients received
      IC, and out of them 90 (77.6%) were males. Median age at diagnosis was 43 years
      (range 31-62 years). Nearly 103 (88.8%) of our patients received doublet
      chemotherapy and the rest of the patients received triplet regimen. Majority of
      the patients had buccal mucosa cancers (71.6%), followed by gingivobuccal complex
      (21.6%) and oral tongue (6.9%) primaries. After IC, partial response was achieved
      in 20 (17.3%) patients, stable disease in 68 (58.6%) patients, and disease
      progression was noted in 28 (24.1%) patients. Post-IC, resectability was achieved
      in 22 (19%) of 116 patients, but 6 of them did not undergo surgery due to
      logistic and personal reasons. The median OS of patients who underwent surgery
      followed by adjuvant local therapy (n = 16) was 19.7 months (95% confidence
      interval [CI]: 16.0-22.8 months) and for those treated with nonsurgical local
      therapy (n = 100) was 7.1 months (95% CI: 5.8-8.2 months) (log-rank P = 0.000).
      CONCLUSIONS: IC had a manageable toxicity profile and achieved resectability in
      19% of our patients with T4b OSCC. Patients underwent resection had a
      significantly better median OS than those who received nonsurgical local
      treatment.

PMID- 29199660
TI  - A study of changes in the oral fungal flora of patients on radiotherapy for head
      and neck malignancies and their correlation with funguria and fungemia.
AB  - BACKGROUND: Patients of head and neck malignancies often develop oral mucositis
      and invite various pathogens to colonize over it. OBJECTIVES: The objective of
      this study is to identify the fungi isolated from patients undergoing
      radiotherapy (RT) for head and neck cancer, to determine the antifungal
      susceptibility of these isolates and to determine the time and week of fungal
      colonization. PATIENTS AND METHODS: Three specimens (throat, urine, and blood)
      were collected from each of the head and neck cancer patients, who were advised
      RT. These specimens, which were collected before the start of RT, during RT (2nd
      and 6th week), and post-RT (8th week) were inoculated into fungal culture media.
      Candida species were identified by standard methods and antifungal susceptibility
      of the candidal isolates was done. RESULTS: Candida infection was found in 24/42
      patients (57.14%) out of which Candida albicans was isolated in 14.28%, Candida
      tropicalis (28.57%) and Candida parapsilosis (14.28%). Maximum isolation of yeast
      was in the 6th week of RT. Fungemia was found in 3/42 patients. All the yeast
      isolates were sensitive to fluconazole except two. CONCLUSION: Prophylactic
      antifungal therapy in patients undergoing RT for head and neck malignancy is
      particularly important to prevent intraoral colonization and infection by
      Candida. Screening of such patients on RT for fungal infections can prevent fatal
      mold infections.

PMID- 29199661
TI  - Related factors of postoperative gallstone formation after distal gastrectomy: A
      meta-analysis.
AB  - AIM: The aim of this study was to evaluate the risk factor of gallstone
      occurrence after distal gastrectomy (DG) for gastric cancer. METHODS: Relevant
      documents published from 2000 to 2016 were retrieved in PubMed, Web of Knowledge,
      and Ovid's database, and a metaanalysis was performed with RevMan 5.0 software
      for odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eight studies
      met the final inclusion criteria. From the pooled analyses, nonphysiological
      reconstruction (OR = 1.51; 95% CI = 1.10-2.08; P = 0.01) and vagus nerve
      resection (OR = 2.79; 95% CI = 1.57-4.96; P = 0.0005) were significantly
      associated with increased risk of gallstone after DG. CONCLUSION: Our analysis
      indicated that digestive tract reconstruction and vagus nerve resection were
      strongly and consistently associated with gallstone formation after DG.

PMID- 29199662
TI  - Efficacy and safety of first-line systemic chemotherapy with epirubicin,
      cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil
      regimens in locally advanced inoperable or metastatic gastric or gastroesophageal
      junction adenocarcinoma: A prospective phase II study from South India.
AB  - BACKGROUND: Patients with locally advanced inoperable or metastatic gastric or
      gastroesophageal junction (GEJ) adenocarcinoma have a poor prognosis. The maximum
      benefit of systemic chemotherapy is usually achieved in the first-line setting.
      Even though systemic chemotherapy has been used for long time, in view of
      unsatisfactory results, no standard regimen has been emerged. Unfortunately, till
      date, there is no published prospective data from India, comparing the two most
      commonly used triplet regimens, epirubicin, cisplatin plus 5-fluorouracil (ECF)
      and docetaxel, cisplatin plus 5-fluorouracil (DCF), in this patient population.
      MATERIALS AND METHODS: The present study aimed to compare the efficacy and safety
      of the first-line systemic chemotherapy with ECF and DCF regimens in locally
      advanced inoperable or metastatic gastric or GEJ adenocarcinoma. The primary
      endpoint was overall survival (OS). The secondary endpoints were overall response
      rate, progression-free survival (PFS), and toxicity profile. RESULTS: Between
      January 2015 and December 2016, 58 patients were assigned and treated with ECF (n
      = 30) or DCF (n = 28) regimens. The median OS was 9.4 months with ECF and 12.5
      months with DCF regimen (log-rank, P = 0.000), while median PFS was 5.8 and 7.5
      months, respectively (log-rank, P = 0.002). Patients in the DCF arm had more
      frequent reductions in chemotherapy doses than those of the ECF arm (28.6% vs.
      16.7%; P = 0.54). As compared with the ECF, the DCF regimen was associated with
      more frequent Grades 3-4 toxicities-neutropenia (16.7% vs. 39.3%, P = 0.17),
      febrile neutropenia (13.3% vs. 25%, P = 0.52), mucositis (6.7% vs. 17.8%, P =
      0.43), and diarrhea (6.7% vs. 14.3%, P = 0.67). CONCLUSIONS: In comparison to
      ECF, the DCF regimen was associated with a statistically significant 3.1 months
      longer median OS without any significant increase in Grades 3-4 toxicities. DCF
      can be considered as one of the reference regimens, in properly selected patients
      with advanced/metastatic gastric or GEJ adenocarcinoma.

PMID- 29199663
TI  - Robotic resections in hepatobiliary oncology - initial experience with Xi da
      Vinci system in India.
AB  - INTRODUCTION: Minimal invasive surgery has proven its advantages over open
      surgeries in the perioperative period. Food and Drug Administration approved da
      Vinci robot in 2000. The latest version, da Vinci Xi system has a mobile tower
      based robot with several modifications to improve the functionality, versatility,
      and operative ease. None of the centers have reported exclusively on
      hepatobiliary oncology using the da Vinci Xi system. We report our initial
      experience. AIMS AND OBJECTIVES: To study the feasibility, advantages, and
      discuss the operative technique of da Vinci Xi system in hepatobiliary oncology.
      MATERIALS AND METHODS: Data were analyzed retrospectively from a prospectively
      maintained database from June 2015 to October 2016. Twenty-five patients with
      suspected or proven hepatobiliary malignancies were operated. Total robotic
      technique using da Vinci Xi system was used. Demographic details and
      perioperative outcomes were noted. RESULTS: Of the 25 surgeries, 14 patients had
      a suspected gallbladder malignancy, 11 patients had primary or metastatic liver
      tumor. Median age was 53 years. The average duration of surgery was 225 min with
      a median blood loss 150 ml. The median postoperative stay was 4 days. The median
      nodal yield for radical cholecystectomy was seven. Five patients required
      conversion. Two of these developed postoperative morbidity. CONCLUSION: Robotic
      surgery for hepatobiliary oncology is feasible and can be performed safely in
      experienced hands. Increasing experience in this field may equal or even prove
      advantageous over conventional or laparoscopic approach in future. A cautious
      approach with judicious patient selection is the key to establishing robotic
      surgery as a standard surgical approach.

PMID- 29199664
TI  - Nivolumab instills hope in a hopeless situation in advanced nonsmall cell lung
      cancer with poor performance status.

PMID- 29199665
TI  - Metastasectomy for recurrent or metastatic biliary tract cancers: A single center
      experience.
AB  - PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent
      or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review
      of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising
      intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile
      duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater
      cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and
      outcomes of BTC patients who underwent surgical resection for the primary and
      metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013
      were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary
      sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three
      patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight
      patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous
      metastasis. The most common metastatic site was liver (nine patients, 47%), lymph
      node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients
      (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and
      R2 resection, respectively. With a median follow-up period of 26.7 months, the
      estimated median overall survival (OS) was 18.2 months (95% confidence interval,
      13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P
      = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P
      = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative
      CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1
      year (P = 0.019) were identified as prognostic factors for a longer OS after
      metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can
      be a viable option for selected patients.

PMID- 29199666
TI  - Metformin use and survival of lung cancer patients: Meta-analysis findings.
AB  - Previous studies on the association between metformin use and lung cancer
      survival have yielded mixed results. We aimed to perform a metaanalysis to assess
      the association with all available studies. Relevant studies were identified by
      searching PubMed and EMBASE to July 2016. We calculated the summary hazard ratios
      (HRs) and 95% confidence intervals (CIs) using randomeffects models. Twelve
      cohort studies involving 124,533 participants were included in this study. The
      results showed that metformin use was not associated with the overall survival of
      lung cancer patients (HR = 0.79, 95% CI: 0.62-1.02). In the subgroup analyses by
      country or subtype of lung cancer, although a beneficial effect of metformin use
      on overall survival was found in patients with smallcell lung cancer or in lung
      patients from China, it may be inappropriate draw a final conclusion considering
      small sample size, low study quality, and the limited number of studies in the
      subgroups. Further analyses found that metformin use after diagnosis showed a
      beneficial effect on both over survival (HR = 0.79, 95% CI: 0.72-0.87) and
      progressionfree survival (PFS; HR = 0.62, 95% CI: 0.39-0.96) of lung cancer
      patients. In conclusion, metformin use after diagnosis is associated with
      improved overall survival and PFS of lung cancer patients. Nevertheless, this
      effect of metformin use is needed for further assessment.

PMID- 29199667
TI  - Mediastinal staging for non-small cell lung cancer revisited. It is being done
      under aegis of ICON and Lung cancer consortium asia.
AB  - Mediastinal staging is a crucial factor in the decision making in patients with
      non-metastatic non-small cell lung cancer (NSCLC). Mediastinoscopy has
      historically been the gold standard for this purpose. With the advent of PET-CT,
      the role of an invasive staging modality like mediastinoscopy has been
      diminishing. Newer developments in endoscopic staging like EBUS and EUS-FNA have
      also provided means to get a cytological diagnosis of enlarged lymph nodes. With
      the meta-analyses showing encouraging results of neoadjuvant chemotherapy in
      operable lung cancers including the early stage disease, the sanctity of invasive
      mediastinal staging for the sole purpose for selecting patients for upfront
      surgery is debatable. This article discusses the various modalities for
      mediastinal staging in NSCLC. We also present our perspective regarding the need
      for a balanced approach between the accuracy of mediastinal staging, invasiveness
      of the staging modalities, and alternate staging methods. With the liberal use of
      neoadjuvant chemotherapy in operable NSCLC, the role of invasive mediastinal
      staging procedures is likely to get limited further, giving way to non-invasive
      staging modalities like PET-CT.

PMID- 29199668
TI  - Is pneumonectomy a justified procedure in patients with persistent N2 nonsmall
      cell lung cancer disease following induction therapy.
AB  - Optimal management and the role of surgery in multimodality treatment for N2
      disease nonsmall cell lung cancer (NSCLC) are controversial. In this review, we
      focus on the possible role of pneumonectomy as a justified procedure in patients
      with persistent N2 disease following induction therapy. We have conducted an OVID
      PubMedbased search including manuscripts published in English for relevant
      studies. The interpretation of these trials highlights the lack of clarity and
      consistency in our management and leaves areas of controversy. There are no Level
      1 data to support either performing or not performing pneumonectomy in this
      setting. The majority of the literature reviewed stresses the high risk of
      mortality and morbidity following pneumonectomy as a part of a trimodality
      approach to Stage IIIA/N2 NSCLC disease. However, selected highvolume
      institutions do follow this strategy with the level of risk seemingly justifying
      it for a highly selected group of patients, and this approach to Stage III/N2
      NSCLC can be offered safely with acceptable mortality. Patient selection,
      response rate to induction therapy, and R0 resection are crucial for survival in
      experienced centers.

PMID- 29199669
TI  - Fluorodeoxyglucose-avid pulmonary mucinous adenocarcinoma presenting with
      nonfluorodeoxyglucose-avid cystic brain lesions of unknown etiopathology: Brain
      magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography
      computed tomography imaging features and additional value of whole-body positron
      emission tomography acquisition.

PMID- 29199670
TI  - Targeted therapy in nonsmall cell lung cancer.
AB  - Activating mutations in the epidermal growth factor receptor gene and
      rearrangement of the anaplastic lymphoma kinase gene exemplify the molecular
      characterization of nonsmall cell lung cancer (NSCLC), particularly
      adenocarcinoma, and its therapeutic relevance. Several genetic alterations with
      prognostic and predictive role, including ROS, RET, MET, KRAS, have now been
      identified in adenocarcinoma and some such as DDR2 and fibroblast growth factor
      receptor 1 in squamous cell carcinoma. This has heralded the development of
      agents targeted against these aberrations. Better knowledge of tumor biology and
      development of targeted agents has ushered an era of personalized treatment
      strategies in NSCLC, leading to improvements not only in tumor control and
      duration of life but also in quality of life.

PMID- 29199671
TI  - Indian consensus statement for treatment of advanced non small cell lung cancer:
      First line, maintenance, and second line.
AB  - The management of advanced nonsmall cell lung cancer (NSCLC) patients is becoming
      complex with the identification of driver mutations and targeted therapies. The
      expert group of academic medical oncologists used data from published literature,
      practical experience to arrive at practical consensus recommendations to treat
      advanced NSCLC for use by the community oncologists.

PMID- 29199672
TI  - A meta-analysis: Evaluation of safety and efficacy of the epidermal growth factor
      receptor-tyrosine kinase inhibitor monotherapy versus platinum-based doublets
      chemotherapy in East Asia.
AB  - OBJECTIVE: Several clinical trials have shown that advanced nonsmall cell lung
      cancer (NSCLC) patients can benefit from treatment with epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy than receiving platinum
      based doublets chemotherapy in the first-line treatment of advanced NSCLC; the
      objective of this study was to evaluate whether patients could be treated with
      EGFR-TKI for advanced NSCLC in the first-line setting. PATIENTS AND METHODS: A
      literature search was conducted on the Cochrane Controlled Trials Register
      Databases, MEDLINE, EMBASE, Web of Science databases, and Chinese Biomedical
      Literature Database without exclusion of material published in any language. We
      performed a meta-analysis of five randomized studies that compared EGFR-TKI with
      platinum-based doublets chemotherapy for the patients of advanced NSCLC in the
      first-line setting. The primary end-point was the progression-free survival (PFS)
      of each treatment arm. The secondary end-points were overall survival (OS),
      objective response rate (ORR), adverse effects, and quality of life (qol).
      RESULTS: Five randomized controlled trials totaling 2080 patients were included
      in the review. Meta-analysis results are as follows: There were statistically
      significant differences in overall PFS (hazard ratio [HR] =0.47; 95% confidence
      interval [CI]: [0.27, 0.83], P = 0.009) and the PFS of the EGFR-M + subgroup (HR
      = 0.29; 95% CI: [0.17-0.51], P < 0.0001). Compared with patients receiving the
      platinum-based doublets chemotherapy group, there were no statistically
      significant differences between the two groups with regard to overall OS (HR =
      0.92; 95% CI: [0.80-1.06], P = 0.25). CONCLUSION: Compared with the platinum
      based doublets chemotherapy, EGFR-TKI significantly prolonged PFS, increased ORR,
      improved qol, not significantly increased the nonhematologic toxicity and at the
      same time decreased the nonhematologic toxicity but not significantly increased
      the transaminase toxicity for advanced NSCLC patients in East Asia. Although
      there is convincing evidence to confirm the results mentioned herein, they still
      need to be confirmed by large-sample trials.

PMID- 29199673
TI  - The comparison of thoracoscopic-laparoscopic esophagectomy and open
      esophagectomy: A meta-analysis.
AB  - OBJECTIVE: The objective of this study was to perform a meta-analysis to evaluate
      the effects of thoracoscopic-laparoscopic esophagectomy (TLE) and open
      esophagectomy (OE) in the treatment of esophageal cancer. METHODS: A literature
      search was performed using PubMed, Embase, and Google Scholar databases for
      relevant keywords and the medical subject headings. After we had screened
      further, 13 clinical trials were included in the final meta-analysis. Specific
      odds ratios (ORs), standardized mean differences (SMDs), mean differences (MDs),
      and confidence intervals (CIs) were calculated. RESULTS: The outcomes of
      treatment effects included anastomotic leakage, blood loss, number of lymph nodes
      harvested, and operating time. Comparing OE for esophageal cancer patients, the
      pooled OR of anastomotic leakage was 0.89 (95% CI = [0.47, 1.68]), the pooled SMD
      of blood loss was - 0.56 (95% CI = [-0.77, -0.35]), the pooled MD of lymph nodes
      harvested was - 0.93 (95% CI = [-2.35, 0.50]), and the pooled SMD of operating
      time was 0.31 (95% CI = [0.02, 0.59]). CONCLUSION: TLE was found to significantly
      decrease patients' blood loss. There is no difference of anastomotic leakage and
      the number of lymph nodes harvested between TLE and OE.

PMID- 29199674
TI  - Continuous hyperfractionated accelerated radiotherapy using modern radiotherapy
      techniques for nonsmall cell lung cancer patients unsuitable for chemoradiation.
AB  - INTRODUCTION: The continuous hyperfractionated and accelerated radiotherapy
      (CHART) regimen of radiotherapy (RT) for nonsmall cell lung cancer is underused
      outside the UK. We present the first Indian experience of using CHART for
      patients, who were not suitable for chemotherapy or concurrent chemo-RT. METHODS:
      We retrospectively reviewed the data of patients treated using CHART at our
      institution between January 2014 and December 2015. RESULTS: Thirty-seven
      patients were treated using CHART. Planning methods and dosimetry parameters are
      described. Three-dimensional conformal RT was used for treatment planning and
      delivery in 23 patients and volumetric modulated arc RT was necessary for 14
      patients. Patients in our series had a median age of 70 years (interquartile
      range 65.50-74.00) and 86.5% had Stage III disease. Median follow-up was short at
      13.0 months. Actuarial rates of 1-year progression-free survival, 1-year overall
      survival (OS), and 2-year OS were 31.9%, 59.5%, and 28.5%, respectively. This
      treatment was well tolerated with manageable and some reversible acute esophageal
      toxicity (91.9% CONCLUSION: Our results indicate that CHART is feasible, safe,
      and well tolerated in Indian patients who are clinically found to be not suitable
      for either sequential or concurrent chemo- RT.

PMID- 29199675
TI  - Development and validation of a predictive score, for identifying poor eastern
      cooperative oncology group performance status (performance status 3-4) advanced
      nonsmall cell lung cancer patients who are likely to benefit from tyrosine kinase
      inhibitors.
AB  - BACKGROUND: One of the ten advanced lung cancer patients presents with poor
      eastern cooperative oncology group performance status (ECOG PS). There are no
      clear guidelines about management of these patients. The benefit of tyrosine
      kinase inhibitors (TKI) in this patient population remains questionable. Hence,
      in this study, we attempted to develop and validate a predictive score which
      would predict benefit from oral TKI. METHODS: This was a prospective
      observational study done at Tata Memorial Hospital, India. Patients with nonsmall
      cell lung cancer with ECOG PS 3-4 were included in this study. All these patients
      had received oral TKI on compassionate grounds and were followed up till death.
      The overall survival (OS) was calculated from date of start of TKI to date of
      death. R software was used for development and validation of the predictive
      model. RESULTS: The median survival duration of the discovery cohort and
      validation cohort were 170.5 and 115 days, respectively. The model predicted OS
      accurately, within +/-2 months in 72.1% and within +/-3 months in 81.7% of
      patients. CONCLUSION: The current model can predict OS in poor PS patients
      treated with TKI within a satisfactory clinical range and can be used for
      decision-making of these patients.

PMID- 29199676
TI  - Epidermal growth factor receptor positive lung cancer: The nontrial scenario.
AB  - PURPOSE: The aim of this study was to report the median overall survival (OS) in
      epidermal growth factor receptor (EGFR) mutation-positive patients who were
      managed out of a clinical trial. METHODS: Nonsmall cell lung cancer patients
      harboring activating EGFR mutations who were either ineligible or refused
      participation in a clinical trial were selected for this analysis. The reason for
      not participating in trial, staging, treatment, and outcome details were obtained
      from a prospective lung cancer database. The Kaplan-Meier method was used to
      estimate OS. Log-rank test and Cox proportion hazard model were used for
      univariate and multivariate analysis, respectively. RESULTS: We included 225
      patients in this analysis. The median age of the cohort was 56 years (range 29-85
      years). A compromised Eastern Cooperative Oncology Group performance status (PS)
      of >2 was the major reason (83 patients, 36.9%) for ineligibility of patients in
      a clinical trial. The major reason provided by eligible patients for refusal to
      participate in a clinical trial was long distance of travel and inability to
      comply with the study-mandated follow-up visits (65 patients, 28.9%). The median
      OS in patients with PS 0-2 was 18.17 months (95% confidence interval [CI]: 15.6
      20.8 months) and it was 12.1 months (95% CI: 9.0-15.2 months) in patients with PS
      3-4 (hazard ratio - 0.579 [95% CI: 0.398-0.843] P = 0.004). CONCLUSION: EGFR
      positive patients who were ineligible for a clinical trial due to poor PS had
      lower survival; however, patients with good PS treated off-trial had similar OS
      to that reported in multiple clinical trials.

PMID- 29199677
TI  - Effect of tyrosine kinase inhibitors on the glucose levels in diabetic and
      nondiabetic patients.
AB  - CONTEXT: Tyrosine kinase inhibitors (TKIs) are used in different types of cancers
      due to their good profile of adverse reactions and their convenience in the oral
      administration. Some studies describe that certain TKIs are associated with
      changes in the glycemic profile of the patients. AIMS: This study aims to
      determine if treatment with ITK affects to serum glucose levels in clinical
      practice. SETTINGS AND DESIGN: A retrospective study was carried out in 136
      episodes (112 patients treated with sorafenib, sunitinib, imatinib, dasatinib, or
      nilotinib). SUBJECTS AND METHODS: The serum glucose levels were analyzed before
      treatment and after months 1, 2, 3, 6, 9, and 12 of treatment. STATISTICAL
      ANALYSIS USED: Statistical analysis was completed with SPSS version 20 for
      Windows. RESULTS: There were significant differences in the serum glucose levels
      before treatment between diabetic and nondiabetic patients, but not between the
      average blood glucose readings before treatment and the average of the subsequent
      readings, once their treatment had begun. CONCLUSIONS: The results of this study
      do not reproduce the results of the literature since changes in the serum glucose
      levels have not been found in this sample of patients.

PMID- 29199678
TI  - Ceritinib in anaplastic lymphoma kinase-positive nonsmall cell lung cancer among
      patients who were previously exposed to crizotinib: Experience from the Indian
      subcontinent.
AB  - Ceritinib is a novel ALK inhibitor approved for advanced stage NSCLC with ALK
      gene rearrangement, progressed and/or intolerant to crizotinib. 13 patients were
      included in our study who received ceritinib. Majority of them were women and
      never smokers with a median age of 47 yrs. Nearly half of them had a compromised
      performance status and received ceritinib in third line and beyond. Ceritinib
      showed nearly 50% response rates. With a median follow up of 9 months for the
      entire cohort, median PFS and OS were not reached. However, the mean values for
      PFS and OS were 10.9 and 14.8 months,with an estimated 1 year PFS and OS being
      56% and 78% respectively.1/3 of the patients had gastrointestinal and liver
      toxicities. Metabolic abnormalities were seen in 1/4 th of them. ceritinib was
      permanently discontinued in one patient due to pneumonitis. In conclusion,
      ceritinib has a favorable efficacy and side effect profile in our patient
      population., similar to that reported in large clinical trials. It has shown
      promising efficacy even in patients with compromised performance status; presence
      of brain metastases and heavily pre-treated disease.

PMID- 29199680
TI  - Actual gains in dosimetry and treatment delivery efficiency from volumetric
      modulated arc radiotherapy for inoperable, locally advanced lung cancer over five
      field forward-planned intensity-modulated radiotherapy.
AB  - AIMS: Volumetric modulated arc radiotherapy (VMAT) is used for inoperable,
      locally advanced nonsmall cell lung cancer, where three-dimensional conformal
      radiotherapy (3D-CRT) cannot yield an acceptable plan. METHODS: The planning and
      treatment data were prospectively collected on the first 18 patients treated
      using VMAT plans. We analyzed the actual dosimetric gain and impact on treatment,
      compared with complex multisegment 3D-CRT (five-field forward-planned intensity
      modulated radiotherapy [IMRT]) that were generated for treatment. Proportion of
      planning target volume (PTV) receiving 95% dose (PTV-V95%) conformity index (CI),
      conformity number (CN), dose homogeneity index (DHI), monitor units (MUs), and
      treatment time were also analyzed. RESULTS: The PTV coverage (PTV-V95%) was
      improved from a median of 91.41% for 5-F forward-IMRT to 98.25% for VMAT (P <
      0.001). The CI improved with a mean of 1.12 for VMAT and 1.31 for 5-F forward
      IMRT (P < 0.001). The mean DHI improved from 1.15 for forward-IMRT to 1.08 for
      VMAT (P < 0.001). The mean CN improved from 0.62 for forward-IMRT to 0.87 for
      VMAT (P < 0.001). No significant increase in the low-dose bath (V5, V10 and mean
      lung dose) to the lung was seen. Significantly higher number of MUs (P < 0.001)
      and shorter treatment delivery times (P = 0.03) were seen with VMAT. CONCLUSION:
      VMAT resulted in improvement in target volume coverage, demonstrated by PTV-V95%,
      CI, CN, and DHI, without any increase in the low-dose bath to the lung. For
      conventional fractionation, VMAT requires more MUs (P < 0.001) but has a shorter
      treatment delivery time (P = 0.03) per fraction.

PMID- 29199679
TI  - A comparative analysis of immunohistochemistry and fluorescent in situ
      hybridization assay to detect anaplastic lymphoma kinase status in lung
      adenocarcinoma cases: A search for a testing algorithm.
AB  - INTRODUCTION: Testing for echinoderm microtubule-associated protein-like 4 (EML4)
      anaplastic lymphoma kinase (ALK) translocation by fluorescence in situ
      hybridization (FISH) is well established whereas the Food and Drug Administration
      (FDA) ALK immunohistochemical (IHC) test is relatively new. AIMS AND OBJECTIVE:
      The aim of this study is to compare FDA-approved ALK IHC test (D5F3 clone) with
      the standard ALK FISH test. MATERIALS AND METHODS: A validation and a test arm
      with 100 and 200 cases of Formalin-Fixed, Paraffin-embedded blocks of lung
      adenocarcinoma, respectively, comprised the material. All cases had ALK IHC test
      on automated Ventana Benchmark XT IHC slide stainer using anti-ALK D5F3 rabbit
      monoclonal primary antibody; when positive tumor cells (any percentage) showed
      strong granular cytoplasmic staining. For the FISH test, Vysis ALK Dual Color
      Break Apart Rearrangement Probe (Abbott Molecular Inc.,) was used to detect ALK
      gene 2p23 rearrangements; when positive the red and green signals were split two
      signal diameter apart and/or isolated 3'red signal were detected in more than 15%
      tumor cells. The ALK FISH results were available in all 100 validation cases and
      64-test arm cases which formed the basis of this analysis. RESULTS: The ALK IHC
      test was positive in 16% cases; four discordant cases were ALK IHC positive but
      ALK FISH negative, but no case was ALK IHC negative and ALK FISH positive. There
      was 100% sensitivity, 90.5% specificity, and 93.75% accuracy. CONCLUSION: A
      negative ALK IHC result obviates the need for a FISH test barring those with a
      strong clinical profile, and a positive ALK IHC result is sufficient basis for
      the initiation of treatment.

PMID- 29199681
TI  - Comparison study of quality of life in advanced lung cancer patients on tyrosine
      kinase inhibitor and platinum doublet chemotherapy.
AB  - INTRODUCTION: Lung cancer is most common cause of cancer death in the world. Most
      of the patient are diagnosed in the late stages and receive only palliative
      treatment. The main objective of the palliative chemotherapy is to improve
      survival as well as the quality of life (QOL). QOL is the most neglected
      dimension of cancer care in developing countries like India. Palliative
      chemotherapeutic agent which has minimum toxicity and prolongs the survival of
      metastatic cancer patients is the need of the day. MATERIALS AND METHODS: In this
      study, 43 metastatic adenocarcinoma of lung patients of South Indian origin were
      enrolled. Twenty patients out of this 43 were epidermal growth factor receptor
      (EGFR) mutation positive and were started on tyrosine kinase inhibitor (TKI).
      Rest 23 patients were EGFR mutation negative and were started on various platinum
      based doublet chemotherapy. QOL was measured using Cancer Institute QOL
      Questionnaire version 2 at the beginning of therapy and at the end of 3 months.
      RESULTS: Our study showed that metastatic lung cancer patients had average QOL at
      presentation. The QOL in patients on TKI improved compared to those on platinum
      doublet chemotherapy during the second assessment, but this improvement was
      statistically not significant. CONCLUSION: In this study, the metastatic lung
      cancer patients had an average QOL during initial presentation. Patients on TKI
      had a trend toward better QOL after 3 months of treatment compared to platinum
      doublet chemotherapy.

PMID- 29199682
TI  - Lung cancer: Presentation and pattern of care in a cancer center in South India.
AB  - BACKGROUND: In India lung cancer is the most commonly diagnosed malignancy in
      males and an increasing trend in the incidence is reported from the National
      Cancer Registry programme. AIMS: The aim of this study is to find out the recent
      trends in presentation and management of lung cancer at Regional Cancer Centre,
      Trivandrum. METHODS: Published reports of hospital based cancer registries (HBCR)
      and population based cancer registries (PBCR) of Trivandrum were compared with
      reported statistics from other parts of India and global data. RESULTS: Lung is
      the leading site of cancer in males (15%) getting treatment at Regional Cancer
      Centre , Trivandrum in 2013 as per the HBCR. There is an increase in the age
      adjusted incidence rate of lung cancer among males in the Trivandrum PBCR from
      14.6 to 18.5 during 2012 -2014. Among the patients who were treated at the Center
      majority (55.2%) presented with distant metastases with adenocarcinoma as the
      most common histological type (28.5%) and only 15.7% had undergone treatment with
      curative intent. CONCLUSIONS: Lung cancer is the major cancer affecting males in
      India with a high incidence in Trivandrum and a very low percentage of patients
      receiving curative treatment which could be due to the high prevalence of
      tuberculosis and scarce availability of facilities and trained manpower for
      thoracic oncology.

PMID- 29199683
TI  - Gemcitabine and carboplatin in metastatic nonsmall cell lung cancer: Experience
      from a tertiary cancer center in South India.
AB  - BACKGROUND: Gemcitabine and carboplatin combination is widely used as one of the
      first-line chemotherapeutic regimens in patients with metastatic nonsmall cell
      lung cancer patients. METHODOLOGY: A total of 112 patients with metastatic
      disease were recruited. They were on standard 21-day gemcitabine 1.2 g/m2 and
      carboplatin AUC 5 dosing schedule. Each patient received at least four cycles and
      a maximum of 6 cycles of treatment. The patients were followed up, and the
      demographic, efficacy and toxicity profiles were analyzed. RESULT: The mean age
      was 53.81+/-9.85 with 71 male and 41 female patients. Response assessment was
      done in 82 patients, and the objective response rate was found to be 47.6% with
      39 partial responders, 20 patients with stable disease and 23 patients with
      progressive disease. The median overall survival was 12 months (95% CI 9.89
      14.11). We found anemia (62.5%) to be more prominent than the other toxicities
      followed by thrombocytopenia and vomiting (31.3%). The nonhematological
      toxicities were minimal and manageable. CONCLUSION: Treatment with gemcitabine
      and carboplatin is efficacious with manageable toxicity profile in the real world
      non-clinical trial setting.

PMID- 29199684
TI  - The increasing challenge of never smokers with adenocarcinoma lung: Need to look
      beyond tobacco exposure.
AB  - BACKGROUND: Lung cancer continues to remain as one of the leading causes of
      morbidity and mortality worldwide, despite the decreasing trends in smoking
      prevalence worldwide. An earlier study from the authors' institute reported the
      increasing trends of "Nonsmoking associated lung cancers." MATERIALS AND METHODS:
      All consecutive histologically confirmed patients with lung cancer who presented
      to the outpatient department over a year (November 2014-October 2015) were
      included in this current prospective study. RESULTS: Seven hundred and thirteen
      patients presented with clinicoradiologically suspicious findings of lung cancer
      in the said period. A pathological confirmation of lung cancer could be
      ascertained in 495 patients, and this cohort was further analyzed. The mean age
      of presentation was 57.76 years; the male to female ratio was approximately
      2.5:1. Interestingly, 55.35% of the patients were nonsmokers. Adenocarcinoma
      (63%) was the predominant histology. Never smokers, both among men (P = 0.02) and
      women (P = 0.001), presented more frequently with adenocarcinoma histology.
      Further, 84.9% (45/53) of rural and 76.1% (19/25) of urban women who were never
      smokers reported exposure to indoor air pollution (secondhand smoke/fuel used for
      cooking purposes) which was significantly associated with adenocarcinoma
      histology. CONCLUSION: Our study confirmed our initial observation of the
      changing epidemiology of lung cancer in the Indian subcontinent, paralleling the
      global trends of rise in adenocarcinoma. Lung cancer in never smokers
      outnumbering that among smokers was another interesting observation. The take
      home message for both the clinicians as well as the policymakers is to study
      factors beyond tobacco exposure to understand the direction of the current lung
      cancer epidemic.

PMID- 29199685
TI  - Role of crizotinib in c-mesenchymal-epidermal transition-positive nonsmall cell
      lung cancer patients.
AB  - The increasing cases of NSCLC and improved understanding of its molecular biology
      has lead to identification of its varied driver mutations. cMET amplification has
      an important role as resistance mechanism for EGFR TKIs. Crizotinib is a drug
      which shows its anti-tumoral effect in cMET positive cases. Here we present a
      case series of three such patients who achieved were cMET amplified and showed
      partial response on Crizotinib.

PMID- 29199686
TI  - First-line therapy outcomes in patients with advanced stage nonsmall cell lung
      cancer treated at nongovernment tertiary care centrer in India: Experience from a
      real world practice.
AB  - INTRODUCTION: Reports on first line or subsequent treatment and their outcomes
      for patients with advanced nonsmall cell lung cancer (NSCLC) in India are scarce.
      The present study is an attempt to understand real world practice scenario of
      first-line therapy and outcome in advanced stage NSCLC patients. METHODS:
      Observational study was conducted at a nongovernment tertiary cancer care center.
      Totally 83 patients with newly diagnosed advanced NSCLC who were evaluated for
      further treatment from 2008 onward were included in the study. RESULTS: Best
      supportive care was the only treatment received in 11/83 patients. Sixty-three
      patients received platinum-based doublet chemotherapy and nine received epidermal
      growth factor receptor tyrosine kinase inhibitor (TKI) as first-line therapy.
      Pemetrexed and platinum was the most common first-line chemotherapy (56%) regimen
      used. First-line chemotherapy had to be discontinued in these eight patients due
      to Grade III/IV toxicity. Disease control rate with the first-line chemotherapy
      was 70% (partial response 38%, stable disease 32%). Median overall survival (OS)
      was 17 months with OS at 1 and 2 years was 52% and 29.5%, respectively.
      CONCLUSION: First-line platinum-based chemotherapy is feasible and does achieve
      disease control in the majority of patients with advanced NSCLC. Strategies of
      selection of therapy based on histology and the presence of driver mutations, use
      of small molecule TKI, maintenance therapy and multiple lines of therapies are
      being increasingly implemented in clinical practice and thus improving survival
      of Indian patients of NSCLC.

PMID- 29199687
TI  - Practical solutions to epidermal growth factor receptor tyrosine kinase inhibitor
      dose modifications in resource-constrained settings: Thinking outside the
      (packaging) box.

PMID- 29199688
TI  - Study of gefitinib maintenance in unselected patients with metastatic primary
      lung adenocarcinoma: A descriptive study.
AB  - BACKGROUND: Maintenance treatment of patients with advanced nonsmall cell lung
      cancer (NSCLC) without disease progression after first-line chemotherapy is a
      subject of ongoing research. The aim of this study was to investigate the
      efficacy, safety, and tolerability of the epidermal growth factor receptor (EGFR)
      tyrosine-kinase inhibitor, i.e., gefitinib in the maintenance setting
      irrespective of EGFR status. METHODS: Patients aged 18 years or older of Indian
      origin, who had a life expectancy of >12 weeks with histologically or
      cytologically confirmed Stage IV NSCLC, the WHO performance status of 0-2, and
      who had completed four to six cycles of first-line platinum-based doublet
      chemotherapy without disease progression or unacceptable toxic effects were
      included in the study. The primary endpoint of the study was progression-free
      survival in the intention-to-treat population. RESULTS: Twenty-five patients with
      a median age of 55 years (40-68) were included in the study. The median
      progression-free survival (PFS) for the entire group was 8 months (95% confidence
      interval [CI] =1.45-14.54) had not reached for EGFR-positive patient, but in the
      EGFR negative cohort, the PFS was 4.98 months (hazard ratio = 0.092, 95% CI = 3.4
      6.5, P = 0.01). The median overall survival (OS) of the study group was 15 months
      (95% CI = 3.7-26.4), all patients with EGFR positive were alive (100% survival).
      The median OS for EGFR negative group was about 6.3 months. The major toxicity
      observed was rash/acne in 15 patients, pruritus in 7 patients, and one patient
      had Grade 4 pneumonitis. CONCLUSION: Gefitinib maintenance is safe, well
      tolerated therapy, produces significant PFS and OS benefit in EGFR mutation
      positive patient. It is definitely not a choice for EGFR negative group. In EGFR
      unknown group, the role of maintenance still needs to be explored.

PMID- 29199689
TI  - Clinical profile of nonsmall cell lung carcinoma patients treated in a single
      unit at a tertiary cancer care center.
AB  - BACKGROUND: Recent advances and understanding in the field of lung cancer and
      advent of newer treatments have shown a significant improvement in survival in
      the patients. The present study was conducted to analyze the clinical profile of
      nonsmall cell lung cancer (NSCLC) patients treated in a single unit at a tertiary
      cancer care center. MATERIALS AND METHODS: In this retrospective analysis, 322
      consecutive NSCLC patients from the year 2011 to 2012 treated in a single unit
      were included in the study. Patients with proven NSCLC were included in the
      study. The details of the patients included the demographic profile, pathological
      diagnosis as well as imaging data, tumor profile, details of treatment, and
      follow-up information. RESULTS: The majority of the patients (95.6%) were in the
      age group >40 years. A large group of the patients (57.1%) were present/reformed
      smokers. The major histological type was adenocarcinoma (60.9%), of which 22.8%
      patients were found to be epidermal growth factor receptor positive. Anaplastic
      lymphoma kinase rearrangement positivity rate was 4.8%. Furthermore, 68% patients
      had Stage 4 disease. Upfront palliative chemotherapy (CT) was offered in 61.8%
      patients and pemetrexed with platinum compounds was the main CT regimen (46.6%).
      Partial response was achieved in 45.7% patients, whereas stable disease was
      observed in 10.9% cases. Median progression-free survival was 5 months and
      overall survival was 55% at 36 months. CONCLUSION: NSCLC forms the largest
      subgroup of lung cancer with the patients presenting with advanced stages of
      disease. This area needs to be explored for the early detection and subsequently
      the radical treatment of the patients. Personalized approach may be considered
      for the management of lung cancer by identifying new predictive and prognostic
      biomarkers of this disease.

PMID- 29199690
TI  - Clinical profile and outcomes of patients with Stage IV adenocarcinoma of lung: A
      tertiary cancer center experience.
AB  - BACKGROUND: There is limited Indian data on clinical profile and treatment
      outcomes for patients with Stage IV adenocarcinoma of lung. AIM: We aimed to
      prospectively study the clinical profile and treatment outcomes for patients with
      Stage IV adenocarcinoma of lung at a tertiary cancer center. MATERIALS AND
      METHODS: One hundred and ninetyfour patients with Stage IV adenocarcinoma of lung
      were prospectively analyzed for demographic and molecular profile (epidermal
      growth factor receptor [EGFR] and echinodermal microtubuleassociated proteinlike
      4anaplastic lymphoma kinase [EML4ALK] mutations). Patients with EGFR and EML4ALK
      mutations were treated with tyrosine kinase inhibitors. Patients without these
      mutations were treated with standard chemotherapy regimens. Maintenance
      chemotherapy was offered to patients as per standard guidelines. Clinical
      outcomes measured were response rate (RR), progressionfree survival (PFS), and
      overall survival (OS). RESULTS: Median age of patients was 56 years (range, 26
      82) with a male:female ratio of 2.3:1. EGFR and ALK mutation testing was feasible
      in 169 (87.1%) and 164 (84.5%), respectively, and detected in 37.9% and 5.5%
      patients, respectively. Overall RR, PFS and OS of whole cohort were 44.3%, 6.9,
      and 15.5 months, respectively. PFS and OS of mutated group (EGFR, EML4ALK) were
      longer than nonmutated group (10.5 vs. 5.4 months, P < 0.0001 and 21.5 vs. 11
      months, P = 0.0001, respectively). PFS and OS of patients who received pemetrexed
      maintenance were longer than those who did not receive maintenance (8.5 vs. 6.5
      months, P = 0.1613 and 18.5 vs. 12.5 months, P = 0.0219, respectively).
      CONCLUSIONS: Mutation testing at diagnosis is feasible in the vast majority of
      patients with Stage IV adenocarcinoma of the lung. Patients with EGFR or EML4ALK
      mutation and those who received pemetrexed maintenance had better clinical
      outcomes.

PMID- 29199691
TI  - New insights into anaplastic lymphoma kinase-positive nonsmall cell lung cancer.
AB  - BACKGROUND: A novel fusion gene of echinoderm microtubule-associated protein-like
      4 (EML4) and anaplastic lymphoma kinase (ALK) has been identified in a subset of
      non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 fusion gene
      demonstrate unique clinicopathological and physiological characteristics. Here we
      present an analysis of clinicopathological profile of patients of metastatic
      adenocarcinoma harboring the ALK-EML4 fusion gene and their response to targeted
      therapy in the form of crizotinib. METHODS: A retrospective analysis of advanced
      ALK positive NSCLC, who presented at this tertiary care hospital of armed forces
      from September 2014 to December 2016 was conducted. The primary goal was to
      evaluate demographic and clinicopathological profile of ALK positive advanced
      NSCLC. Detection of ALK fusion was done by IHC on formalin fixed paraffin
      embedded cell blocks. Out of 20 ALK positive patients, ten patients received
      upfront cytotoxic chemotherapy, and rest received crizotinib. Patients
      progressing on cytotoxic chemotherapy received crizotinib as subsequent therapy.
      RESULTS: Out of 270 patients of NSCLC, fifteen(7.4%) tested positive for ALK-EML4
      fusion. Rate of positivity was higher in females(13.7%) than in males (5%). The
      correlation of the ALK-EML4 fusion gene and clinicopathological characteristics
      of NSCLC patients demonstrated a significant difference in smoking status,
      histological types, stage, & metastatic pattern. Median PFS with first line
      cytotoxic chemotherapy was 5.9 months. Median PFS with upfront crizotinib was not
      reached, but was significantly superior than cytotoxic chemotherapy. CONCLUSION:
      Our analysis indicated that ALK-EML4 positive NSCLC comprised a unique subgroup
      of adenocarcinomas with distinct clinicopathological characteristics. Incidence
      of ALK positivity was found to be higher in females and never smokers. These
      patients have distinct pathological and radiological characteristics. Crizotinib,
      whether used upfront or as subsequent therapy was found to be superior in PFS
      (not yet reached at the time of writing this article), and maintaining quality of
      life as compared to cytotoxic chemotherapy.

PMID- 29199692
TI  - Anaplastic lymphoma kinase immunohistochemistry in lung adenocarcinomas:
      Evaluation of performance of standard manual method using D5F3 antibody.
AB  - OBJECTIVE: Immunohistochemistry (IHC) with anaplastic lymphoma kinase (ALK)
      antibodies is considered as an economical screening method in lung
      adenocarcinomas. Automated Ventana D5F3-IHC is approved by US Food and Drug
      Administration for targeted therapy; however, the automated IHC apparatus are not
      widely used in most laboratories. We evaluated the performance of ALK IHC using
      the manual semiquantitative method to assess the concordance with Ventana ALK IHC
      assay. MATERIALS AND METHODS: We tested 156 cases of primary lung adenocarcinomas
      for ALK protein expression by D5F3-IHC. The intensity of cytoplasmic staining was
      classified as 0 or 1+/2+/3+ (weak/medium/strong). Binary score of positive and
      negative was used for Ventana assay. A comparison analysis and
      clinicopathological features were recorded. RESULTS: ALK IHC was positive in 25
      (16.02%) cases, of which 18 were men and mostly nonsmokers. The mean age for all
      patients was 55 years, and for ALK IHC-positive cases was 48 years. Nine of 25
      (36%) ALK IHC-positive cases showed signet ring cell and mucinous morphology. On
      comparison, all, but one, cases positive by manual method showed positive results
      by automated assay. IHC negative cases by manual method were negative by Ventana
      assay. CONCLUSION: Manual IHC is equally effective in the detection of ALK
      rearranged cases as automated methods. It can be easily integrated as a screening
      method into routine practice thus reducing the cost of automated systems.
      However, equivocal cases should be tested by approved methods.

PMID- 29199693
TI  - Atypical lung carcinoid: An unusual presentation.

PMID- 29199694
TI  - Retrospective analysis of icotinib neoadjuvant therapy of 63 lung cancer
      patients.
AB  - OBJECTIVE: This study aims to explore the feasibility of icotinib neoadjuvant
      therapy for nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a
      retrospective analysis of the clinical data for 63 NSCLC patients (61 cases of
      adenocarcinoma and two cases of squamous cell carcinoma) receiving surgical
      resection of lung lesions after oral intake of icotinib from December 2011 to
      November 2013 in the PLA General Hospital. Preoperative oral intake of the
      patients was icotinib 125 mg tid, drug side effects were evaluated according to
      the American National Cancer Institute Common Toxicity Criteria Version 4.0;
      computed tomography scan was done on the day taking medicine and 2 weeks later to
      determine tumor changes. After oral intake of Icotinib for 2 to 22 weeks (5 cases
      for 2 weeks,13 cases for 3 to 22 weeks), all patients receive surgical resection
      of lung cancer lesions, and testing of removed tumor to evaluate the epidermal
      growth factor receptor (EGFR) gene mutation status was performed by fluorescence
      polymerase chain reaction. The patients with sensitive EGFR mutations receive
      Icotinib as postoperative adjuvant therapy. RESULTS: Side effects of medication
      within 2 weeks included rash (44.4%, 28/63), dry skin (34.9%, 22/63), diarrhea
      (14.3%, 9/63), and oral ulcer (1.6%, 1/63); there were no icotinib-associated
      thoracic surgery complications during the perioperational period. 71.4% patients
      (45/63) achieve an average reduction of 23.5% +/-10.7%(10%-53.5%) after 2 weeks
      medication of Icotinib(regressive tumor[RT]) .28.6% patients(18/63) achieve
      stable tumor(ST),enlargement of 8.7% to reduction of 8.7% of the maximum diameter
      of lung cancer after 2 weeks medication of Icotinib. Of the RT group, 68.9%
      (31/45) of the tumors were detected with EGFR-sensitive mutation (exon 19 or 21
      mutation), 24.4% (11/45) with wild-type EGFR, and three cases of exon 20
      mutation. Of the ST group, 77.8% (14/18) were detected with wild-type EGFR, three
      cases of exon 20 mutation, and one case of exon 19 deletion mutation (tumor
      reduction by 7.9%). 45 cases in RT group and 1 case with EGFR 19 exon metation in
      ST group receive Icotinib as adjuvant therapy. Among 45 cases in RT group and 18
      cases in ST group, there was no difference in gender, age, smoking history, tumor
      diameter, tumor differentiation degree, and incidence of side effects (P =
      0.076). There was significant difference (P < 0.0001) in terms of symptom
      remission rate after medication and EGFR gene-sensitive mutation rate in RT and
      ST groups. CONCLUSION: Icotinib neoadjuvant therapy for NSCLC is safe and
      feasible, and the reactivity of lung cancer patients to icotinib can be
      determined within 2 weeks of medication. People sensitive to preoperative
      selection of drugs can more accurately determine the sensitivity of tumors to
      drugs, thus providing evidence for postoperative adjuvant therapy.

PMID- 29199695
TI  - The efficacy and safety of preoperative chemotherapy for patients with nonsmall
      cell lung cancer: A meta-analysis.
AB  - BACKGROUND: The efficacy of surgery alone for patients with nonsmall cell lung
      cancer (NSCLC) is still unsatisfactory. Preoperative chemotherapy (PCT) is proven
      effective induction therapies followed by surgery; however, few their superiority
      remains uncertain. We performed a systemic review and meta-analysis to evaluate
      the safety and efficacy of the PCT for NSCLC patients. MATERIALS AND METHODS: A
      literature search was performed in the PubMed, China National Knowledge
      Infrastructure and Cochrane databases. NSCLC patients treated with PCT plus
      surgery (PCT-S) or surgery (S) alone between 2006 and 2016 were analyzed.
      RESULTS: A total of eleven studies, involving a total of 2999 patients, were
      finally enrolled in this meta-analysis. Meta-analysis shows that PCT-S might have
      lower recurrence rate than S (odds ratio [OR] = 0.75, 95% confidence interval
      [CI] [0.60, 0.94], P = 0.01). However, no differences were found between two
      groups in overall survival rate (OR = 1.26, 95% CI [0.92, 1.72], P = 0.15) and
      (OR = 1.12, 95% CI [0.93, 1.33], P = 0.23), 3-year disease-free survival rate (OR
      = 1.22, 95% CI [0.73, 2.04], P = 0.44) and intraoperative and postoperative
      complication rates (OR = 1.24, 95% CI [0.89,1.74], P = 0.20). CONCLUSIONS: Two
      treatments have similar safety and efficacy. However, PCT can reduce the rate of
      local and distant recurrence, which is an independent risk factor for NSCLC
      prognosis and may improve the prognosis of NSCLC.

PMID- 29199696
TI  - Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A
      single-institution experience from South India.
AB  - Wide use and incorporation of newer diagnostic tools in the management of
      metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of
      personalized treatment of this disease. With the wide use of polymerase chain
      reaction and fluorescence in situ hybridization increasing number of patients are
      being diagnosed with dual and complex mutations posing a new challenge in the
      management of patient with metastatic NSCLC. In this article, we would like to
      bring forth six such cases and the varied responses to the current available
      treatment in patients with complex and dual mutations. The appropriate management
      in these groups of patients is yet to be standardized.

PMID- 29199697
TI  - Anaplastic lymphoma kinase status in lung cancers: An immunohistochemistry and
      fluorescence in situ hybridization study from a tertiary cancer center in India.
AB  - BACKGROUND AND OBJECTIVES: Fluorescence in situ hybridization (FISH) and
      immunohistochemistry (IHC) have shown good concordance for the detection of
      echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase
      (ALK) rearrangement. Since studies reporting FISH/IHC concordance,
      clinicopathological features, and clinical outcomes of ALK-positive patients from
      India are lacking, this study was undertaken. MATERIALS AND METHODS: This is a
      retrospective, observational study of patients with adenocarcinoma of the lung on
      whom ALK test was performed between March 2013 and December 2015. ALK status was
      assessed in 341 patients by FISH using Vysis ALK Dual Color Break Apart
      Rearrangement Probe and IHC using ALK D5F3 clone. Clinicopathological features
      were noted. Patients were managed as per the standard guidelines. Clinical
      outcomes - response rate (RR) and progression-free survival (PFS) - were
      measured. RESULTS: ALK rearrangement was positive in 37 patients (10.9%). ALK
      positivity was observed more commonly in younger patients with no predilection
      for any gender or any specific histological subtype. ALK by IHC was highly
      sensitive (100%), compared to FISH with concordance rate of 94.4%. Thirty one of
      thirty seven (31 of 37) patients received therapy of which 3 patients received
      palliative chemotherapy and 28 patients received tyrosine kinase inhibitors
      (crizotinib/ceritinib). Overall RR observed was 77.4%, and median PFS had not
      been reached at a median follow-up of 12.5 months. INTERPRETATION AND
      CONCLUSIONS: We report higher frequency of ALK positivity (10.9%) in patients
      with adenocarcinoma of the lung. ALK by IHC is more sensitive than FISH for ALK
      detection with high concordance. These patients had good clinical outcome with
      TKIs targeting ALK fusion protein.

PMID- 29199698
TI  - Role of pneumonectomy for lung cancer in current scenario: An Indian perspective.
AB  - BACKGROUND: Surgical treatment for lung cancer has evolved from pneumonectomy to
      lobectomy/sleeve resection around the world. Although condemned for poor
      outcomes, pneumonectomy may still be required in a select group of patients in
      developing countries. With the better patient selection, optimization of medical
      comorbidities, better perioperative care; pneumonectomy may show better results.
      Thus, there is a need to reconsider the role of pneumonectomy in patients with
      locally advanced lung cancer in the current scenario. PATIENTS AND METHODS: The
      aim of this study was to analyze the demographic and clinicopathologic profile of
      lung cancer patients and the role of pneumonectomy at a tertiary cancer center in
      India. The records of patients, who underwent surgery for lung cancer at our
      institute from January 2011 to April 2014, were analyzed retrospectively, and
      various parameters in pneumonectomy were compared to lobectomy patients. RESULTS:
      Out of 48 patients undergoing major lung resections, nearly 80% patients were
      symptomatic at presentation and were mostly in advanced stages, thus requiring
      neoadjuvant chemotherapy in 45.8% cases and pneumonectomy in 41.6% patients.
      There was no difference in morbidity and mortality in pneumonectomy (25%, 5%)
      versus lobectomy (21.2%, 3.5%). Disease-free survival at 1, 2, and 3 years after
      pneumonectomy (71.8%, 51.4%, and 42.8%) was comparable to lobectomy (73.3%,
      66.1%, and 55.6%). After neoadjuvant therapy, survival was not affected by the
      type of surgery. CONCLUSIONS: In the Indian scenario, as the majority of lung
      cancer patients present at an advanced stage, pneumonectomy still plays a major
      role, and the acceptable postoperative outcome can be achieved with aggressive
      perioperative management.

PMID- 29199699
TI  - A prospective study of telephonic contact and subsequent physical follow-up of
      radically treated lung cancer patients.
AB  - BACKGROUND: We tested the hypothesis that telephonic follow-up (FU) may offer a
      convenient and equivalent alternative to physical FU of radically treated lung
      cancer patients. DESIGN: Prospective study carried out at a tertiary referral
      cancer care institute, Mumbai. MATERIALS AND METHODS: Two hundred consecutive
      lung cancer patients treated with curative intent were followed up regularly with
      telephonic interviews paired with their routine physical FU visits. Patient
      satisfaction with the telephonic call and the physical visit, the anxiety level
      of the patient after meeting the physician and the economic burden of the visit
      to the patient were noted in a descriptive manner. Kappa statistics was used to
      assess concurrence between the telephonic and physical impression of disease
      status. RESULTS: With a median FU duration of 21.5 months, the median
      satisfaction scores for telephonic and physical FU were 8 and 9, respectively.
      The prevalence and bias adjusted kappa (PABAK) score of the entire cohort of
      patients was 0.64 (95% confidence interval [CI] =0.58-0.70). Data analyzed up to
      first disease progression/relapse on FU had a PABAK score of 0.71 (95% CI = 0.64
      0.77) indicating substantial agreement. Patients with disease controlled at the
      FU had a significant PABAK score of 0.88 (95% CI = 0.80-0.94) indicating
      excellent concurrence. On average, each patient spent Rs. 5117.10 on travel and
      Rs. 3079.06 on lodging per FU visit. CONCLUSION: Telephonic FU is substantially
      accurate in assessing disease status until the first relapse. In a resource
      constrained country like India, it is worthwhile to further explore the benefits
      of such an alternative strategy.

PMID- 29199700
TI  - Chemosuppressive effect of plumbagin on human non-small lung cancer cell
      xenotransplanted zebrafish.
AB  - BACKGROUND: Plumbagin (5-hydroxy-2-methyl-1,4-napthoquinone) derived from
      Plumbago species is a potential anti-tumour agent. Plumbagin has been tested for
      anti-cancer activity in vitro and in vivo using mice model. AIM: To study the
      tumour suppressing efficacy of plumbagin using zebrafish model. MATERIALS AND
      METHODS: Human Non-small lung cancer cell line were cultured in vitro and
      transplanted in to zebrafish. The development of tumour was confirmed by
      performing histology. The tumour was then allowed to progress in vivo and the
      fishes were administered with plumbagin orally for three continuous days. The
      tumour suppression capacity was monitored subsequently using transcriptosome
      analysis. STATISTICAL METHODS: The pixel integrated density obtained was
      converted into relative gene expression using IBM SPSS. RESULTS: The
      administration of plumbagin had an ability to suppress tumour and the size of the
      tumour were relatively lesser when compared with the control sample; it has also
      increased p53 gene expression. CONCLUSION: The study helps to conclude that
      plumbagin is an effective anti-tumour agent against human cancer cells based on
      the study in vivo in zebrafish.

PMID- 29199701
TI  - Demographic, clinical, biochemical, radiological and etiological characteristics
      of malignant pleural effusions from Eastern India.
AB  - CONTEXT: There are very limited data regarding clinical, radiological and
      etiological aspects of malignant pleural effusion (MPE) from Eastern India. AIMS:
      To review natural history, clinical features, radiological features and etiology
      of MPEs. SETTING AND DESIGN: Hospital based cross-sectional descriptive study.
      MATERIALS AND METHODS: We had reviewed166 diagnosed cases of MPEsregarding
      demography; clinical, radiological and biochemical characteristics, diagnostic
      modalities and etiologies. RESULTS: Out of 166 patients, 72.89% were males and
      27.11% were females. Mean age of presentation among males was 64.3 +/- 12.7 and
      among females was 52.5 +/- 14.8. Most common presenting symptom was dry cough
      (87.9%) and most common presenting sign was clubbing (54.5%). Massive effusion
      was found in 45.78% of cases. Pleural fluid macroscopic appearance was
      haemorrhagic in 54.82% of cases. Mean adenosine deaminase activity in MPE was
      24.05 U/L. Mean pleural fluid/serum protein ratio was 0.65, mean pleural
      fluid/serum lactate dehydrogenase ratio was 1.01. Most of the cases (84.94%) were
      diagnosed by pleural fluid cytology for malignant cells. Primary cancer was
      diagnosed in 136 (81.93%) cases; among which 121 (88.97%) cases were lung
      cancers, among which adenocarcinoma (52.89%) was the most common histology.
      CONCLUSIONS: Pleural fluid cytologies for malignant cells are usually sufficient
      to diagnose MPE in nearly 85% of cases and in remaining cases if thoracoscopyis
      not available, blind pleural biopsy can be helpful. The most common primary in
      cases of MPE is lung cancer with adenocarcinoma being the commonest culprit.

PMID- 29199702
TI  - Palliative thoracic radiotherapy in advanced lung cancer: A single institution
      experience.
AB  - BACKGROUND: Majority of patients of lung cancer present with locally advanced or
      metastatic disease, where systemic therapy is the treatment of choice. Many of
      these patients have local symptoms due to thoracic disease, wherein radiotherapy
      is proven to be an effective modality for alleviation of symptoms. However, the
      optimal dose of radiotherapy for adequate palliation remains debatable. The
      purpose of this retrospective study was to assess the efficacy of two different
      schedules of thoracic radiotherapy (TRT) with respect to symptom palliation.
      MATERIALS AND METHODS: A total of 100 consecutively treated patients with stages
      III-IV lung cancer treated with two different fractionation regimens of
      palliative TRT, either protracted course 20 Gy/5# over 1 week or short course of
      17 Gy/2# over 8 days were assessed for symptom relief and survival. Impact of
      patient, tumor and treatment-related factors on response and overall survival
      (OS) was done by univariate analysis using log-rank test. RESULTS: Median age of
      the entire cohort was 60 years, majority being males, smokers with low Eastern
      Cooperative Oncology Group performance status (performance score >=2).
      Predominant symptoms were chest pain (68) followed by cough (21) and dyspnea
      (15). Palliative TRT was offered as either protracted course 20 Gy/5# over 1 week
      or short course of 17 Gy/2# over 8 days in 21 and 79 patients respectively.
      Median duration of symptom relief was 2 months, no differences in OS at 1 year
      with either regimen. CONCLUSIONS: TRT is an effective means of palliation having
      similar symptom relief and outcomes with weekly (17 Gy/2# over 8 days) or
      protracted radiotherapy regimens (20 Gy/5#over 1 week). Short TRT schedules are
      convenient and economical for patients as well as resource sparing for high
      volume centers.

PMID- 29199703
TI  - Metastatic nonsmall cell lung cancer in South India: A regional demographic
      study.
AB  - BACKGROUND: Nonsmall cell lung cancer (NSCLC) has varying epidemiological
      patterns in different countries and also in different regions of each country. In
      a country with a high prevalence of lung cancer such as India, regional
      variations in demography exist. AIM: A study of unique demographic trends of
      metastatic NSCLC patients presenting to our regional cancer center. MATERIALS AND
      METHODS: We did a retrospective analysis of histologically confirmed metastatic
      NSCLC patients who presented to our Department of Medical Oncology between August
      2012 and July 2014. RESULTS: A total of 304 patients were analyzed. About 55.6%
      of the patients were in the age group of 41-60 years. About 79.6% of the patients
      were symptomatic for <6 months before presentation. About 63.5% of the patients
      were smokers presenting with a median age of 59 years whereas nonsmokers formed
      36.51% of the patients presenting with a median age of 47 (P < 0.001). About
      82.6% of the male patients and 4.1% of female patients were smokers. Equal number
      of all patients had adenocarcinoma (AC) and squamous cell carcinoma (SCC)
      histology. AC histology was more common in the nonsmoking group (62% of
      patients). SCC histology was seen in 54.3% of smokers. Metastasis to the
      contralateral lung and pleura was seen in 58.2% of patients. CONCLUSION: NSCLC
      presents at a young age. Smoking is a significant risk factor and it is common in
      the urban populations as in the rural areas. Both AC and SCC histologies
      presented in equal proportions.

PMID- 29199704
TI  - Solitary pulmonary nodule evaluation in regions endemic for infectious diseases:
      Do regional variations impact the effectiveness of fluorodeoxyglucose positron
      emission tomography/computed tomography.
AB  - BACKGROUND: Fluorodeoxyglucose positron emission tomography/computed tomography
      (FDG-PET/CT) has become a preferred imaging modality for the evaluation of
      solitary pulmonary nodule (SPN), particularly in the developed world. Since FDG
      can concentrate in infective/inflammatory lesions, the diagnostic utility of FDG
      PET can be questioned, particularly in regions endemic for infectious decisions.
      AIM: To evaluate the accuracy of FDG-PET/CT in evaluation of SPNs in a population
      endemic for infectious disease and to assess if regional variations have an
      impact on its effectiveness. MATERIALS AND METHODS: All patients who underwent an
      FDG/PET-CT with a clinico-radiological diagnosis of SPN categorized as
      indeterminate were included. Based on a maximum standardized uptake values
      (SUVmax) cut-off of 2.5, lesions were classified as benign (<2.5) or malignant
      (>2.5) and compared with gold standard histopathology. The diagnostic accuracy of
      PET-CT to detect malignancy was calculated. On the basis of final histopathology,
      lesions were grouped as (a) malignant nodules (b) infective/granulomatous nodules
      with a specific diagnosis and (c) nonspecific inflammatory nodules. The
      SUVmaxbetween these groups was compared using nonparametric statistical tests.
      RESULTS: A total of 191 patients (129 males, 62 females) with a median age of 64
      years (range: 36-83) were included. Totally, 144 nodules (75.3%) were malignant
      and 47 were benign (24.7%). Adenocarcinoma (n = 84) was the most common
      malignancy. Tuberculosis (n = 16) and nonspecific infections (n = 24) were the
      two most common benign pathologies. There was a significant overlap in the
      metabolic uptake of malignant (median SUVmax-11.2, range: 3.3-34.6) and
      tuberculous nodules (median SUVmax-10.3, range: 2.7-22.5) with no statistically
      difference between their SUVmaxvalues (P = 0.43). The false-positive rate was
      65.2% and the false-negative rate was 5.5%. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of FDG-PET/CT
      for detecting malignancy were 94.4%, 34.7%, 81.9%, 66.6%, and 79.5%,
      respectively. CONCLUSIONS: Though FDG-PET scans show a very high sensitivity for
      malignant nodules, it has a high false-positive rate and reduced specificity when
      characterizing SPNs in an infectious endemic region. Physicians must be aware of
      this limitation in the workup of lung nodules, and regional variations must be
      considered before further management decisions are taken.

PMID- 29199705
TI  - Outcomes in lung cancer: An experience from routine tertiary care setting.
AB  - BACKGROUND: The aim of this study was to establish characteristics of lung cancer
      patients diagnosed at a tertiary care hospital in Bangalore. METHODS: The
      retrospective study was undertaken comprising of 202 patients diagnosed of
      advanced lung cancer in a tertiary care setting. Data was analyzed to identify
      patients' characteristics, smoking history, tumor histology, stage of the
      disease, treatment received, and survival rates. RESULTS: Among the 202 patients
      diagnosed, 134 were males, and 68 were females. Tumor histology testing revealed
      that 168 patients had adenocarcinoma, 24 patients had squamous carcinoma, 5
      patients had small cell carcinoma, and 5 patients were poorly differentiated
      carcinoma. Among the patients of adenocarcinoma, complete response, partial
      response (PR), stable disease, and progressive disease (PD) were seen in 0.6%,
      52%, 17%, and 23.2% of the patients respectively. The median progression-free
      survival (PFS) for first-line treatment was 6.5 months; the highest PFS was seen
      with nab-paclitaxel/platinum combination. The mean overall survival was 11.7
      months and the highest OS of 12.3 months with gefitinib therapy. In the squamous
      subset of patients, PR was observed in fourteen patients, of which five patients
      were treated with nab-paclitaxel/platinum. The mean overall survival of 10.5
      months and mean PFS was 6.2 months with the highest PFS of 6.8 months were seen
      with weekly nab-paclitaxel. Among the small cell lung cancer patients, nine were
      treated with etoposide/platinum regimen with a compliance of 6 cycles. Three
      patients had a PR, and one had a PD on etoposide/platinum regimen. The mean
      overall survival in these patients was 4.6 months.

PMID- 29199706
TI  - Repeat biopsy in epidermal growth factor receptor mutation-positive nonsmall cell
      lung cancer: Feasibility, limitations, and clinical utility in Indian patients.
AB  - INTRODUCTION: The feasibility and success rate of repeat biopsy for epidermal
      growth factor receptor (EGFR) mutation-positive lung cancers that have progressed
      on tyrosine kinase inhibitors (TKIs) are varied and merits further assessment.
      MATERIALS AND METHODS: EGFR mutation-positive lung cancers were offered repeat
      biopsy upon progression on TKIs. Two groups of patients, first one on a clinical
      trial and second one from a database, were included for analysis. The feasibility
      to perform a repeat biopsy was analyzed in the first group. Success rate of
      biopsy and tissue adequacy for molecular testing was analyzed in both groups.
      Descriptive statistics were used for analyzing the demography, EGFR mutation
      type, tissue adequacy, and molecular profile at repeat biopsy. Kolmogorov-Smirnov
      test was used to assess normality of data. Two sample t-tests were used for
      comparison of proportions. RESULTS: The feasibility of undergoing repeat biopsy
      was 77% (95% confidence interval [CI] of 69.4%-83.5%) in the first group (114/148
      patients). Feasibility was not analyzed in the second group of patients. Out of
      196 patients who underwent a repeat biopsy, 154 patients (78.6%; 95% CI: 72.2%
      84.1%) had tumor tissue adequate for performing molecular testing. 27/196 (13.8%)
      patients did not have any evidence of malignancy on repeat biopsy whereas 15/196
      (7.6%) patients had scanty tissue on repeat biopsy prohibiting molecular testing.
      Six patients (3.06%; 95% CI: 1.1%-6.5%) had small cell transformation. T790M
      mutation was detected in 12 out of the 42 patients (28.6%; 95% CI: 15.7-44.6) in
      whom EGFR testing was performed on repeat biopsy specimen. CONCLUSION: Repeat
      biopsy was able to provide adequate tissue acquisition in only two-thirds of the
      patients. Liquid biopsy represents an important tool to bridge this gap.

PMID- 29199707
TI  - Evolving epidemiology of lung cancer in India: Reducing non-small cell lung
      cancer-not otherwise specified and quantifying tobacco smoke exposure are the
      key.
AB  - BACKGROUND: Adenocarcinoma is the most prevalent histological type of lung cancer
      (LC) in developed countries while squamous cell carcinoma (SqCC) has so far been
      the most common type at our center. Herein, we report our continued assessment of
      the epidemiological trend of LC aimed at determining any change in the
      histological distribution. METHODS: Retrospective analysis involving all
      consecutive newly diagnosed LC patients over a 4-year period (March 2011-February
      2015). Demographic characteristics, histology, and staging data for current data
      set were compared with our previously published data (2008-2011). As before,
      smoking index (SI) was used to group patients as never (SI = 0), light (SI = 1
      100), moderate (SI = 101-300), and heavy (SI >=301) smokers. RESULTS: Majority of
      1301 patients had advanced disease (Stages IIIB = 30.1%; IV = 53.3%), were males
      (82.3%) and current/ex-smokers (76.9%). Adenocarcinoma and SqCC (36.4% each) were
      equally prevalent. As compared to our previous study, adenocarcinoma increased
      (36.4% vs. 27.5%) and nonsmall cell lung cancer-not otherwise specified (NSCLC
      NOS) decreased (5.1% vs. 10.9%) significantly (P < 0.001). The current study had
      more heavy smokers (68.3% vs. 61.1%; P = 0.013) and median SI was also higher
      (500 vs. 400; P = 0.001). Among SI-based groups, significant differences were
      observed for age, gender, body mass index, histology, TNM stage, and metastatic
      disease distribution. CONCLUSION: Reduction in NSCLC-NOS has led to
      adenocarcinoma and SqCC being equally prevalent at our center in North India
      despite an increase in heavy smokers. Accurate histological NSCLC subtyping is
      necessary for optimal epidemiological assessment.

PMID- 29199708
TI  - The single-incision versus multiple-incision video-assisted thoracoscopic surgery
      in the treatment of lung cancer: A systematic review and meta-analysis.
AB  - OBJECTIVE: We conducted this meta-analysis to compare the clinical outcomes of
      single-incision and multiple-incision video-assisted thoracoscopic surgery (VATS)
      lobectomy for lung cancer patients. METHODS: A literature search was conducted of
      the Cochrane Controlled Trials Register Databases, Medline, EMBASE, Web of
      Science databases, and Chinese Biomedical Literature Database. Eleven studies
      that compared single-incision VATS with multiple-incision VATS in the treatment
      of lung cancer were analyzed. Statistical analysis was carried out using RevMan
      5.1 software. RESULTS: Eleven trials totaling 1273 patients were included. There
      were statistically significant differences in the duration of chest tube
      (standardized mean difference [SMD] = -0.42; 95% confidence interval [CI] [-0.78,
      -0.07], P < 0.02), hospital stays after surgery (SMD = -0.28; 95% CI [-0.41, 
      0.15], P < 0.0001), hospital stays after surgery in the subgroup analysis of
      lobectomy (SMD = -0.28; 95% CI [-0.42, -0.14], P < 0.0001), length of wound (P <
      0.05), and pain visual analog scale (VAS) in the postoperative 1 day (SMD = 
      1.19; 95% CI [-1.94, -0.44], P = 0.002) between single-incision VATS group and
      multiple-incision VATS group. Compared with patients receiving multiple-incision
      VATS group, there were no statistically significant differences between the two
      groups with regard to the operative time (OT), blood loss (BL), rate of
      conversion to thoracotomy, and complication. CONCLUSION: Compared with multiple
      incision VATS on the condition of same lymph nodes retrieved number, single
      incision VATS reduced the length of wound, shortened the duration of chest tube,
      cut down the hospital stays after surgery, alleviated the pain VAS in the
      postoperative 1 day, did not significantly increase the OT and the BL in
      operation, and did not increase the rate of conversion to thoracotomy and
      complication.

PMID- 29199709
TI  - Stereotactic body radiation therapy for early-stage primary lung cancer, is an
      active breath coordinator necessary? An audit from a tertiary cancer care center.
AB  - CONTEXT: The hypofractionated stereotactic body radiation therapy (SBRT) has
      emerged as a safe and effective treatment modality for early-stage nonsmall cell
      lung carcinoma. AIMS: An audit SBRT in primary lung cancer treated in our center
      with and without an active breath coordinator (ABC) was undertaken to evaluate
      its impact on target volumes and clinical outcomes. SETTINGS AND DESIGN: This was
      an observational study. MATERIALS AND METHODS: Nine patients with lung carcinoma
      were treated from January 2014 to August 2016. Five patients were simulated using
      ABC and four patients with free breathing. Volumetric modulated arc therapy plans
      were generated using Monaco treatment planning software. Three patients were
      treated with a dose of 54 Gy in three fractions and six patients with a dose of
      48 Gy in four fractions. STATISTICAL ANALYSIS USED: The statistical analysis was
      performed using Kaplan-Meier survival. RESULTS: The mean planning target volumes
      (PTV) in ABC and free breathing groups were 42.19cc and 60.17cc, respectively.
      The mean volume of lung receiving 20, 10, and 5 Gy (V20, V10and V5) in ABC group
      were 5.37cc, 10.49cc, and 18.45cc whereas in free breathing 6.63cc, 12.74cc, and
      20.64cc, respectively. At a median follow-up of 18 months, there were three local
      recurrences. No significant toxicity occurred in our series. CONCLUSION: Our
      initial results show that SBRT is well tolerated with good local control.
      Although the PTV volume and irradiated normal lung volume was higher in this
      group compared to ABC group, this did not translate to any added clinical
      toxicity.

PMID- 29199710
TI  - Incidence and characteristics of Epidermal Growth Factor Receptor (EGFR) mutation
      in non-small-cell lung cancer (Adenocarcinoma histology): A report of 106
      patients from Kolkata.
AB  - CONTEXT: Regional epidemiological data regarding the epidermal growth factor
      receptor (EGFR) mutation status in non-small-cell lung cancers (NSCLC) is an
      unmet need from the eastern part of India. AIMS: To report the incidence of EGFR
      mutation and its correlation with the phenotypical characteristics, in NSCLC
      patients from Kolkata. SUBJECTS AND METHODS: NSCLC patients, with adenocarcinoma
      histology, whose tissues had been tested for EGFR mutational status between March
      2014 and February 2017, were considered for this study. The testing methods used
      were Real-time-based amplification refractory mutation system, polymerase chain
      reaction (ARMS PCR), PCR and gene sequencing, and cell-free DNA (CTDNA). Clinical
      characteristics and treatment details were collected from the patient's medical
      records in a de-identified manner. STATISTICAL ANALYSIS USED: Data were analyzed
      using simple descriptive statistical methods. RESULTS: Between March 2014 and
      February 2017, 108 samples were tested and two were deemed inadequate for
      reporting. Of the remaining 106 patients, 65 (61.3%) were males, and 41 (38.6%)
      were females. Median age was 56 years (42-72), 59 years for males and 52 years
      for females. 73.6% were nonsmokers. 87.7% tests were done using the real-time
      ARMS-PCR; 9.4% underwent PCR and gene sequencing and 2.8% using CT-DNA. Of 106
      patients, 35 (33%) patients were found to be EGFR mutation positive. Ratio of
      male:female was 16 (45.7%):19 (54.3%). Ratio of nonsmoker: smoker was 30
      (85.7%):5 (14.3%). 18 patients had exon 19 deletion (51.4%), 15 had L858R exon 21
      mutation (42.9%), 1 patient (2.9%) had mutation in S7681 exon 20 along with L858R
      21 and one patient (2.9%) had a T790m mutation without any other detectable EGFR
      mutation. CONCLUSIONS: The incidence of EGFR mutation in NSCLC is 33% from
      Kolkata and is typically more common in females and nonsmokers.

PMID- 29199711
TI  - Venous thromboembolism in cancer patients - magnitude of problem, approach, and
      management.
AB  - Cancer is hypercoagulable state. Patients with cancer are at high risk to develop
      venous thromboembolism (VTE). Relative risk of developing VTE is approximately
      seven times higher in patients with active cancer. The incidence of occult
      malignancy is 7%-12% in patients with idiopathic deep vein thrombosis (DVT).
      However, little research has been focused on cancer with thromboembolism.
      Lowmolecularweight heparin most frequently used pharmacologic agents as
      recommended by established guidelines. The aim was to evaluate the magnitude of
      problem in cancer patients and treatment option as per established guidelines.
      EMBASE, MEDLINE, and PubMed search of the literature were done to evaluate the
      association of DVT with various malignancy, magnitude of problem, approach, and
      various guidelines for the management of DVT. References of all publication were
      also searched to enrich this article for recent update. Thromboprophylaxis in
      cancer patient is gray zone area. This need lot of investigational work to find
      highrisk patients who would benefit from primary thromboprophylaxis.

PMID- 29199712
TI  - Histopathological analysis of meningioma and its variants: A study of fifty
      cases.
AB  - BACKGROUND: The study was conducted to know the various histopathological
      variants of meningiomas, the age incidence and sex ratio. MATERIALS AND METHODS:
      A retrospective and prospective analysis of all the samples sent for
      histopathology for 2 years during June 2013-May 2015 was done to diagnose
      meningioma and its variants. Cases were analyzed in detail about the complete
      clinical history, exact location, and clinical and radiological diagnosis. The
      majority of the cases were clinically and radiologically diagnosed as meningioma.
      RESULTS: Of 50 cases which were diagnosed as meningiomas, 21 were meningothelial
      variant, 15 were psammomatous, 8 were fibroblastic, 4 were transitional, and 1
      case each of anaplastic and atypical variant. The most common age group was
      between 41 and 50 years. The youngest age group was 16 years and oldest was 70.
      The male:female ratio was 1:1.5. CONCLUSION: The majority of the meningiomas have
      been observed between 41 and 50 years. Their proper recognition is therefore
      important to allow appropriate treatment. Histopathological study plays a major
      role by which we can diagnose the lesion. Meningiomas typically develop in middle
      aged individuals and occur more frequently in women than men. These lesions may
      also occur in children.

PMID- 29199713
TI  - Stereotactic body radiation therapy for hepatocellular carcinoma: Experience from
      a tertiary cancer care center in India.
AB  - AIM: The aim of this retrospective study is to assess the toxicity and tumor
      response of stereotactic body radiation therapy (SBRT) protocol for
      hepatocellular carcinoma (HCC) in our institution. BACKGROUND: Hepatocellular
      cancer is one of the leading cancers among men in India. In recent years, SBRT
      has emerged as a promising tool in the treatment of HCC. MATERIALS AND METHODS:
      Ten patients diagnosed as HCC with Barcelona Clinic Liver Cancer Stage B and C,
      treated with SBRT technique from January 2013 to December 2016, were included in
      this study. SBRT was delivered using 6 MV photons with volumetric modulated arc
      therapy. Acute and late toxicities were graded, and tumor response was assessed
      using response evaluation criteria in solid tumors criteria. Kaplan-Meier curves
      were generated for progression-free survival (PFS) and overall survival (OS).
      RESULTS: The median age was 61.5 (52-69) years. The radiation dose ranged from 35
      Gy to 60 Gy. All patients obtained partial response during assessment at 3 months
      after completion of treatment. The median PFS is 8 months (95% confidence
      interval [CI] - 5.22-10.77 months). The median OS is 51 months (95% CI - 17.64
      65.10 months). The OS at 1 and 2 years is 75% and 57%, respectively. CONCLUSIONS:
      SBRT is well tolerated by our patients. The 1- and 2-year OS of 75% and 57% is
      consistent with other prospective and retrospective SBRT studies from the
      literature.

PMID- 29199714
TI  - Prognostic factors and treatment of patients with advanced synovial sarcoma: A
      single-center experience.
AB  - BACKGROUND: Synovial sarcoma (SS) is a malignant mesenchymal tumor, which
      comprises 5%-10% of all the sarcomas. There is insufficient information on
      prognostic factors and salvage treatments of advanced SS. In this study, we aimed
      to further clarify the clinicopathological features, prognostic factors, and
      treatment modalities in advanced SS. MATERIALS AND METHODS: A total of 45 SS
      patients followed up between 2001 and 2015 at our cancer institute, Department of
      Medical Oncology, were retrospectively evaluated. Eleven patients were initially
      metastatic, and remaining patients developed metastasis or became inoperable due
      to locally advanced disease. Overall survival was evaluated by Kaplan-Meier
      analysis. RESULTS: The median age of patients was 37 (17-70) years and 60% (n =
      26) of them were female. SS was most commonly localized in the lower extremity
      and abdomen-pelvis (29% and 29%, respectively). Median follow-up time was 33 (6
      175) months. Patients were treated with a median of two (1-5) line chemotherapies
      at metastatic stage. Ifosfamide plus adriamycin (IMA) (49%, n = 22) and cisplatin
      etoposide (13%, n = 6) were the most often used chemotherapy regimen as first
      line in metastatic stage. Partial response was obtained in 32% of the patients
      treated with IMA chemotherapy. Furthermore, median progression-free survival was
      6 (1-123) months. Median survival of metastatic stage at diagnosis or in follow
      up was 21 months (14-27) and 21 (12-29) months (P = 0.53), respectively. Most
      metastatic locations were lung (75%) and bone. Factors influencing survival at
      metastatic stage were evaluated; statistically significant longer survival was
      observed in patients with lung metastasis, primary tumor size smaller than 10 cm,
      patients who underwent surgery for the metastasis, and development-to-metastasis
      period longer than 12 months. CONCLUSION: Median survival of patients in
      metastatic stage SS was 21 months. Lung was the most common metastatic site.

PMID- 29199715
TI  - Expanded panel test detecting mesenchymal-epithelial transition amplification
      leading to effective treatment in adenocarcinoma lung.

PMID- 29199716
TI  - Pattern of distant metastasis in molecular subtypes of carcinoma breast: An
      institutional study.
AB  - BACKGROUND: Molecular subtypes of carcinoma breast show a particular pattern of
      distant metastasis, the knowledge of which can help to diagnose and intervene
      early in the course of the disease. AIM: The aim of this study was to investigate
      and establish an association between the molecular subtypes of carcinoma breast
      and the pattern of distant metastasis. SETTINGS AND DESIGN: Single arm,
      retrospective study. MATERIALS AND METHODS: Totally 400 patients of carcinoma
      breast (Stage I and II) were selected who were treated between January 2010 and
      December 2013. All these patients were treated with the standard treatment
      protocol for breast cancer. The estrogen receptor, progesterone receptor, human
      epidermal growth factor receptor-2 (HER-2) Neu status, and Ki-67 were done, and
      patients were classified into luminal A/B, HER-2 enriched, luminal/HER-2, and
      triple-negative subtypes. All patients were followed up until December 2015, and
      the pattern of local failure as well as distant metastasis was correlated with
      the molecular subtypes. RESULTS: A total of 143 patients developed distant
      metastasis and local recurrence. Bone was the most common site of metastasis
      overall. It was the most common type of metastasis in luminal A/B (53.3%) and
      luminal-HER (57.1%). Brain metastasis was most common in HER-2-enriched subtype
      (30.3%), whereas liver was the most common site of metastasis in HER-2-enriched
      subtype (45.45%). The incidence of brain metastasis was comparatively lower in
      luminal A/B subtype. Local recurrence was most common in HER-2-enriched subtype.
      The results were statistically significant for lung metastasis and local
      recurrence (with P = 0.004 and 0.047, respectively). CONCLUSION: A strong
      association exists between the molecular subtypes and the site of distant
      metastasis in breast cancer which can be used for greater vigilance to detect
      site-specific distant metastasis beforehand.

PMID- 29199717
TI  - Tumor characteristics and metabolic quantification in carcinoma breast: An
      institutional experience.
AB  - BACKGROUND: In India, carcinoma breast is the most common cancer among urban
      women population and second most common cancer after carcinoma cervix in rural
      areas. One in 22 women in India develops carcinoma of the breast in their
      lifetime. Fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in breast cancer
      usually indicates the degree of tumor metabolism and hence can predict its
      behavior and prognosis. On the other hand, the estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2)
      or neu state of breast cancer is a biomarker that provides important prognostic
      information in addition to predicting response to therapy. AIMS: The main
      objective of this study is to assess whether a correlation exists between 18F-FDG
      uptake in untreated cases of breast cancer, their receptor status (ER, PR, and
      HER-2 or neu), tumor histology, and tumor size. SUBJECTS AND METHODS: Sixty
      consecutive female patients, with biopsy-proven primary breast cancer, were
      enrolled in this prospective study for whom 18F-FDG positron emission tomography
      computed tomography scan was done in the Department of Nuclear Medicine. Results
      obtained were analyzed using appropriate statistical tests (t-test and Pearson
      Chi-square tests), and interpretation was made with 95% confidence level.
      RESULTS: In our series, a positive correlation between tumor size, high tumor
      grade, and standardized uptake value (SUV) was found. Tumors with positive
      receptor status for estrogen, progesterone, and HER-2/neu receptors had
      statistically insignificant lower maximum SUV (SUVmax) values than their negative
      counterparts. Triple-negative breast tumors (ER-, PR-, and no overexpression of
      HER-2/neu) are currently a subject of major interest because of their
      aggressiveness, poor prognosis, and lack of targeted therapy. Based on receptor
      status when the SUVmaxof the group with triple-negative receptor status (ER-/PR
      /HER-2/neu-) was compared to rest of the patient group, it was seen that patients
      with negative receptor status had significantly higher mean SUVmaxvalues.
      CONCLUSIONS: We have inferred that in patients with breast cancer, various
      biological parameters such as tumor size, grade, histology, and hormonal receptor
      status have different impact on tumor metabolic activity.

PMID- 29199718
TI  - Multiple myeloma: Experience of an institute in limited resource setting.
AB  - INTRODUCTION: Multiple myeloma (MM) is a plasma cell dyscrasias and an incurable
      clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The
      mainstay of treatment of myeloma is induction treatment followed by consolidation
      with autologous stem cell transplant (ASCT). However, still in a developing
      country like India where affordability is a major hurdle for health care, a
      number of MM patients are not able to undergo ASCT. AIM: To study the
      epidemiological features and outcome of MM patients treated in a limited resource
      setting. MATERIALS AND METHODS: We conducted a retrospective study at our
      institute to identify patients diagnosed as MM from 2005 to 2016. We studied the
      epidemiological profile and the outcome of the treatment in terms of response
      rates and overall survival. STATISTICAL ANALYSIS: Survival analysis was performed
      using Kaplan-Meier curve. RESULTS: Median age at diagnosis is 54 years (range: 39
      85 years). IgG myeloma was the most common type seen in 72% of patients. The
      International Staging System (ISS) was ISS I (31%), ISS II (30%), and ISS III
      (39%). The median duration of treatment for thalidomide + dexamethasone (TD) and
      bortezomib + TD (VTD) was 9 and 7 months, respectively. Median survival for the
      TD versus VTD regimen (in a nontransplant setting) for the ISS I, ISS II, and ISS
      III groups was 49 and 55 months (P = 0.056), 42 and 48 months (P < 0.05), 21 and
      27 months (P < 0.05), respectively. CONCLUSION: Proteasome inhibitors
      significantly improved the median survival for patients with MM (ISS II and ISS
      III) treated in a limited resource setting.

PMID- 29199719
TI  - Retrospective study of efficacy and safety of neoadjuvant docetaxel, carboplatin,
      and trastuzumab in HER2-positive locally advanced and oligometastatic breast
      cancer: An Indian experience.
AB  - BACKGROUND: The neoadjuvant chemotherapy in HER2-positive breast cancer consists
      of a chemotherapy backbone and HER2-directed therapy. The increase in
      cardiotoxicity by the use of trastuzumab with an anthracycline-based regimen has
      led to the use of nonanthracycline-based alternative regimens. The docetaxel,
      carboplatin, and trastuzumab (TCH) are one such regimen. The efficacy and
      toxicity of this regimen have not been widely studied in Indian patients. AIMS:
      This retrospective study aims to evaluate the efficacy and toxicity of
      neoadjuvant TCH regimen in locally advanced and oligometastatic HER2-positive
      breast cancer in Indian patients. METHODOLOGY: The hospital records between
      January 2014 and December 2016 were reviewed to identify patients with locally
      advanced and oligometastatic HER2-positive breast cancer treated with uniform 3
      weekly neoadjuvant chemotherapy protocol-containing docetaxel (75 mg/m2),
      carboplatin (AUC = 6), and trastuzumab (8 mg/kg loading followed by 6 mg/kg)
      (TCH). The primary outcome was the pathologic complete response (pCR), which was
      defined as an absence of invasive and noninvasive cancer in breast or lymphnode.
      RESULTS: Thirty-two patients with mean age 46 years met our inclusion criteria,
      of these 24 patients had locally advanced breast cancer, and eight patients had
      oligometastatic breast cancer. 13 (40.6%) patients had hormone-positive breast
      cancer. The objective response rate as assessed clinically was 100%, and pCR rate
      was 36.3%. The patients with oligometastatic breast cancer also showed a good
      response to chemotherapy with three patients showing pCR and four patients
      showing resolution disease at metastatic sites. The patients experienced very few
      Grade III/IV toxicities, and no patient had clinical congestive heart failure.
      CONCLUSION: The TCH protocol is an efficacious neoadjuvant chemotherapy regimen
      for locally advanced and oligometastatic breast cancer and is safe and well
      tolerated in this population.

PMID- 29199720
TI  - A prospective randomized trial comparing capecitabine-based chemoradiotherapy
      with 5-FU-based chemoradiotherapy in neoadjuvant setting in locally advanced
      carcinoma rectum.
AB  - INTRODUCTION: Fluorouracil (FU)based chemoradiotherapy is regarded as a standard
      perioperative treatment in locally advanced rectal cancer. Capecitabine is an
      oral fluoropyrimidine that generates 5FU preferentially at the tumor site by
      exploiting the higher activity of the enzyme thymidine phosphorylase in tumor
      tissue compared with healthy tissue. As an oral agent, capecitabine can be
      administered in the outpatient setting, potentially providing FU exposure similar
      to a lowdose continuous infusion of 5FU. AIMS AND OBJECTIVES: To compare
      capecitabine with 5FU, with regard to efficacy and toxicity when used in
      neoadjuvant setting along with radiotherapy for locally advanced carcinoma
      rectum. MATERIALS AND METHODS: Thirty patients were enrolled, 14 in 5FU and 16 in
      capecitabine arm. All patients were planned for 45 Gy/25#/5 weeks pelvic
      radiotherapy followed by a boost of 5.4 Gy/3#/3 days. 5FU was prescribed at a
      dose of 500 mg/m2 #1-#5 and #21-#25 of RT and capecitabine was given at 1650
      mg/m2 on RT days throughout the course of radiotherapy. A magnetic resonance
      imaging/computerized tomography scan was done at the start of treatment and 1
      month after completion of treatment, followed by surgery. Toxicity was assessed
      weekly during treatment and on the first followup. RESULTS: Response rates and
      toxicity profile of capecitabinebased cathode ray tube (CRT) was similar to
      5FUbased CRT with nonsignificant P values. CONCLUSION: Capecitabine may be used
      as an alternative in patients who do not tolerate 5FU.

PMID- 29199721
TI  - Predicting loco-regional recurrence risk in T1, T2 breast cancer with 1-3
      positive axillary nodes postmastectomy: Development of a predictive nomogram.
AB  - BACKGROUND: Role of postmastectomy radiotherapy (PMRT) in early breast cancer
      with 1-3 positive axillary nodes is still controversial. Hence, there is a need
      to identify subgroup of patients who have sufficiently high risk of disease
      recurrence to benefit from PMRT. AIM: The aim is to evaluate clinical outcomes of
      patients postmastectomy having pathological T1-T2 tumors with 1-3 positive
      axillary lymph nodes (LNs) treated with adjuvant systemic therapy and develop a
      predictive nomogram. MATERIALS AND METHODS: Data collected retrospectively from
      eligible patients from 2005 to 2011. Kaplan-Meier survival analysis was used for
      all time-to-event analysis. Various known clinical and pathological risk factors
      were correlated with outcome using uni- and multi-variable analysis in SPSS
      version 21. All comparisons were two-tailed and P < 0.05 were considered
      statistically significant. The nomogram to predict the risk of loco-regional
      control (LRC) was developed using least absolute shrinkage and selection operator
      shrinkage model in hdnom.io software. RESULTS: 38/242 (15.7%) patients had
      recurrent disease at loco-regional (10 patients), distant sites (22 patients) and
      simultaneous loco-regional and distant sites (6 patients) at a median follow-up
      59.5 (range 4-133) months. Five years estimate of LRC, distant disease-free
      survival (DFS), DFS, cause-specific survival and overall survival was 87.8%,
      85.4%, 84.2%, 93.1%, and 91.5%, respectively. Pathological tumor size, margin
      status, LN ratio as continuous variables and grade and triple negative breast
      cancer status as categorical variables were the risk factors included in the
      model for building nomogram. CONCLUSION: The nomogram developed based on
      institutional data can be a valuable tool in guiding adjuvant PMRT depending on
      the risk of 5 years loco-regional recurrence.

PMID- 29199722
TI  - Composite lymphomas: Experience from a tertiary cancer center in Kerala, South
      India.
AB  - OBJECTIVES: Composite tumors are defined as tumors in which there are two
      different intermixed histologic types. Our objective was to study the clinical
      and pathologic features of five cases of composite lymphoma. MATERIALS AND
      METHODS: Our study included five patients of composite lymphoma diagnosed over a
      period of 5 years. Clinical presentation, hematological parameters including
      peripheral smear, bone marrow aspirate, and histopathological examination of
      lymph node including immunohistochemistry (IHC) were studied. Treatment and
      follow-up details were also noted. RESULTS: All the five cases were in the adult
      age group ranging from 44 to 72 years. All the cases were composite follicular
      lymphoma (FL) and mixed cellularity classical Hodgkin lymphoma (CHL). Diagnosis
      in all cases was suspected on morphology by identification of distinct neoplastic
      follicles in FL and classic Reed-Sternberg cells in CHL and confirmed by IHC.
      CONCLUSION: Although rare, composite lymphomas should be kept in mind. Careful
      histopathological examination of lymph node with identification of distinct
      morphological features along with IHC helps to arrive at the definitive
      diagnosis.

PMID- 29199723
TI  - Chemo port insertion through femoral vein approach: A rare indication and a rare
      complication.

PMID- 29199724
TI  - Survival and prognostic factors for glioblastoma multiforme: Retrospective single
      institutional study.
AB  - INTRODUCTION: Glioblastoma multiforme (GBM) is the most common and aggressive
      primary brain tumor in adults. The standard management has been maximum surgical
      resection followed by adjuvant radiotherapy with concurrent chemotherapy followed
      by adjuvant chemotherapy. Although the survival rate of patients with GBM has
      improved with recent advancements in treatment, the prognosis remains generally
      poor. The median survival rates are in the range of 9-12 months and 2-year
      survival rates are in the range of 8%-12%. MATERIALS AND METHODS: A single
      institution retrospective review of 61 patients of GBM from 2012 to 2014. Data
      regarding patient factors, disease factors, and treatment factors were collected
      and survival has been calculated. RESULTS: A total of 61 patients with GBM were
      analyzed. GBM is commonly seen in sixth decade of life. Male to female ratio is
      2.6:1. The right side of the brain is commonly involved with right frontal lobe
      being the most common site. The median follow-up was 4.6 months. The median
      survival of our patients was 8 months. The 1-year and 2-year survival rates were
      20% and 3.27%, respectively. CONCLUSIONS: The overall survival and prognosis in
      patients with GBM remains poor despite of constant research and studies.
      Concurrent chemoradiotherapy followed by adjuvant chemotherapy with temozolomide
      should be used after maximal resection to improve the survival.

PMID- 29199725
TI  - Rechallenge temozolomide in glioma: A case series from India.
AB  - INTRODUCTION: Temozolomide (TMZ) is an integral part of upfront treatment of high
      grade gliomas. It is administered postsurgery as concurrent therapy with
      radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is
      unknown whether rechallenge of salvage TMZ in previously treated high-grade
      glioma has any efficacy. MATERIAL AND METHODS: Patients treated with salvage
      rechallenged TMZ between January 2015 and August 2016 were included for this
      retrospective analysis. SPSS version 20 was used for this analysis. Time to event
      analysis was performed using the Kaplan-Meier method. Progression-free survival
      (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity was
      noted in accordance with CTCAE version 4.02. RESULTS: A total of 23 patients were
      selected for analysis with the median age being 43 years (range: 26-69 years).
      The tumor histopathology at baseline was astrocytoma Grade 2 in 1 patient,
      oligodendroglioma Grade 2 in 3 patients, anaplastic astrocytoma in 7 patients,
      anaplastic oligodendroglioma in 2 patients, and glioblastoma in 10 patients. All
      of them had previously received TMZ. The median numbers of previous TMZ cycles
      received were 6 (4-18). The median time to failure postlast treatment was 24
      months (5-72 months). The median number of cycles of rechallenged salvage TMZ
      administered was 6 cycles (range: 1-18). Grade 3-4 myelosuppression was seen in 3
      patients (13.4%). The median PFS was 459 days (95% confidence interval: 212.1
      705.9). The median OS was 25 months. Six-month OS and 1-year OS were 81.4% and
      75.1%, respectively. CONCLUSION: Rechallenge with TMZ in recurrent glioma that
      had previously responded to TMZ is associated with improvement in PFS and OS and
      has a sufficiently long disease-free interval.

PMID- 29199726
TI  - Role and relevance of BRAF mutations in risk stratifying patients of papillary
      thyroid cancers along with a review of literature.
AB  - INTRODUCTION: Molecular markers are increasingly being explored as a potential
      diagnostic and prognostic tool in patients with well-differentiated thyroid
      cancers and B-type Raf kinase (BRAF) V600E mutation has received a wide attention
      in this regard. Many clinical studies have demonstrated an association of BRAF
      V600E mutation with aggressive clinicopathologic characteristics and high tumor
      recurrence and mortality in patients with papillary thyroid cancers. Papillary
      thyroid cancers has been abbreviated and PTCs. AIM: The present single center
      study aims to assess the biological behavior of conventional papillary thyroid
      cancers. (PTC) with somatic BRAF V600E mutation. MATERIALS AND METHODS: Patients
      who were managed for well differentiated thyroid cancers during 2005-2006 were
      included in the study. BRAF V600E mutation analysis was done by real time
      polymerase chain reaction after extracting genomic DNA from the representative
      archived formalin fixed paraffin embedded tumor tissue. RESULTS: Of the 79
      patients of well-differentiated thyroid cancers included in the study, 31%
      harbored BRAF V600E mutation; the mutation prevalence was 39.6% in the cohort of
      conventional PTCs. Our study emphatically states that BRAF V600E mutation status
      is a significant predictor of adverse outcomes in patients with conventional
      PTCs. CONCLUSION: Our study further suggests a possible risk-stratified approach
      using age, BRAF V600E mutation status, and extrathyroidal spread, and this
      approach can be used to personalize the management of patients with conventional
      PTCs. The result of our study adds to the growing consensus that BRAF V600E
      mutational status should be analyzed in correlation with other molecular and
      clinicopathological prognostic factors for a better risk stratification.

PMID- 29199727
TI  - Evaluation of dose conformity and coverage of target volume for intensity
      modulated radiotherapy of pelvic cancer treatment.
AB  - BACKGROUND: Better conformity may help in delivering minimum dose to organs at
      risk (OARs) and maximum dose to planning target volume (PTV). As per the
      requirements of modern radiotherapy, 95% isodose should cover the PTV, so
      conformity indices (CIs) are used for evaluating quality of conformation of
      treatment plans. AIM: This study aimed to investigate degree of conformity for
      pelvic patients using intensity-modulated radiotherapy (IMRT) technique. Three
      formulas of CIs described in literature were analyzed in this study. SETTINGS AND
      DESIGN: This study was performed to evaluate degree of conformity of 18 patients
      treated with radiotherapy treatment plan using cumulative dose volume histogram.
      Effectiveness of different CIs was explored for IMRT plans using 15 MV photon
      beam. Doses delivered to OAR were also studied. STATISTICAL ANALYSIS USED: CI
      suggested by the International Commission on Radiation Units and Measurements,
      radiation CI and CI prescription isodose to target volume (PITV) had mean +/-
      standard deviation values of 1.02 +/- 0.018, 0.98 +/- 0.017, and 1.63 +/- 0.333,
      respectively. RESULTS AND CONCLUSION: Dose distribution for all patients was
      highly conformal and clinically acceptable. Values of CI PITV exceeded acceptable
      value for 27% patients with minor deviation. No statistically significant
      differences were observed for three CIs reported. Target volume lies between 95%
      and 107% of prescribed dose which shows ideal target coverage. This simple
      parameter is advantageous since it is easy to interpret and helped determine
      quality of treatment plan. This study clearly demonstrated that favorable dose
      distribution in PTV and OARs is achieved using IMRT technique, and hence, the
      risk of damage to normal tissues is reduced.

PMID- 29199728
TI  - Testicular seminoma: Are clinical features and treatment outcomes any different
      in India?
AB  - AIM: This study aims to identify clinical features, treatment outcomes, and
      prognostic factors for relapse and survival in patients with testicular seminoma.
      MATERIALS AND METHODS: Retrospective analysis of all patients with pure seminoma
      treated at our center during over a decade (January 2005-December 2014) was
      carried out. Patient demographics, tumor characteristics, and treatment details
      and pattern of recurrence were recorded in a structured format, and disease-free
      survival and overall survival were calculated. RESULTS: Sixty-three patients'
      case records were included in the analysis. Ten patients developed disease in the
      undescended testis. All patients underwent orchiectomy as the initial treatment
      procedure. Majority of the patients were Stage I (57.14%) followed by Stage II
      (39.6%). Among the patients with Stage I, 55.5% received adjuvant chemotherapy
      while 22.2% received adjuvant radiation and the rest opted for surveillance. The
      compliance for active surveillance was very poor. Among patients with Stage II
      disease, majority (80%) were treated with adjuvant chemotherapy and the rest with
      radiation. At a median follow-up of 49 months, there were four recurrences of
      which three were salvaged successfully, and one patient remained alive with
      disease. There were no disease-related deaths. CONCLUSIONS: Testicular seminoma
      remains to be relatively low and majority of them presented with Stage I disease
      and single agent carboplatin appeared to be the preferred adjuvant treatment.
      Advanced disease patients were treated with etoposide and cisplatin/bleomycin,
      etoposide and cisplatin chemotherapy and the clinical outcome is comparable with
      the Western literature.

PMID- 29199730
TI  - Theoretical aspects of femtosecond double-pump single-molecule spectroscopy. II.
      Strong-field regime.
AB  - We investigate femtosecond double-pump single-molecule signals in the strong
      field regime, which is characterized by nonlinear scaling of the signal with the
      intensity of the pump pulses. The signals can be decomposed into population and
      coherence contributions. In contrast to the weak-field regime (in which only the
      coherence contribution is important) both contributions are relevant in the
      strong-field regime and reveal the vibrational dynamics of the chromophore. Other
      than in the weak-field regime, the detection of vibrational beatings is not
      limited by the electronic dephasing time of the chromophore. Moreover, the
      signals in the strong-field regime are more robust with respect to the
      environment-induced modulation of the chromophore parameters. It is shown that
      excited-state absorption in chromophores with three electronic states is
      reflected in the phase dependence of single-molecule signals. The simulations
      reveal that the information content of femtosecond double-pump single-molecule
      signals is enhanced in the strong-coupling regime.

PMID- 29199729
TI  - Epidemiology of gynecological cancers in Kamrup Urban District cancer registry.
AB  - BACKGROUND: Cancers of the female reproductive system - namely cancer of the
      cervix, corpus uteri, ovarian, vulvar, vaginal, fallopian tube cancers and
      choriocarcinoma are an important cause of cancer morbidity and mortality among
      women worldwide. It is estimated to be the third most common group of
      malignancies in women. The comprehensive global cancer statistics from the
      International Agency for Research on Cancer indicate that gynaecological cancers
      accounted for 20% of the 14.1 million estimated new cancer cases and 8.2 million
      cancer deaths among women in the world in 2012. The estimation of cancer burden
      is necessary to set up priorities for disease control. Gynaecological cancers
      have increased in India and are estimated to be around 182,602 by the year 2020
      constituting about 30% of the total cancers among women in India. Among these,
      cancer of the uterine cervix followed by ovary and corpus uteri are the major
      contributors. METHODS AND MATERIALS: Cancer is not notifiable in India, so method
      of collecting information on cancer was active with voluntary participation of
      different sources including major hospitals, diagnostic centers, state referral
      board and birth and death registration centers within registry area. RESULTS: A
      total of 3767 (44%) cases were registered in women out of the total number of
      8561 cancer cases during the period from 2010-2014. In case of gynaecological
      cancers a total of 661 cases of cervical, ovarian and corpus uterine cancers were
      registered out of the total 3767 female cancer cases (17.5%) for the year 2010
      2014.The annual average crude rate in women for all sites of cancer was 117.4 per
      100000 population. The corresponding AARs was 166.6. CONCLUSIONS: Women's health
      issues have attained high concern in recent decades. Utmost efforts should be
      made to educate women in early cancer detection by creating awareness on risk
      factors and symptoms.

PMID- 29199732
TI  - Carbene-catalyzed LUMO activation of alkyne esters for access to functional
      pyridines.
AB  - A carbene-catalyzed LUMO activation of alpha,beta-unsaturated alkyne esters is
      reported. This catalytic process allows for effective reactions of alkyne esters
      with enamides to synthesize functional pyridines via simple protocols. A
      previously unexplored unsaturated alkyne acyl azolium intermediate is involved in
      the key step of the reaction.

PMID- 29199731
TI  - Ionic liquids at interfaces: general discussion.

PMID- 29199733
TI  - A robust, portable and backflow-free micromixing device based on both capillary-
      and vacuum-driven flows.
AB  - In capillary- or vacuum-driven microfluidics, surge backflow events are common
      when merging or pumping two similar or dissimilar liquids together if a pressure
      difference exists between them. In this work, a robust, portable micromixing
      device that is insensitive to backflow was designed, fabricated and
      characterised. A capillary-driven pressure balancing bypass connected between two
      inlet ports diminished the initial pressure difference caused by capillarity and
      gravity present in each liquid at the two inlet ports. Then, using manual syringe
      assisted vacuum-driven pumping that operated based on the high gas permeability
      of polydimethylsiloxane, the two pre-balanced liquid streams could synchronously
      enter a dead-end micromixing channel without any backflow. To test the
      performance of this device, we first used it to mix two aqueous solutions of
      different coloured dyes. We varied the initial volume difference between the
      solutions to study the effect of gravity-induced pressure difference on mixing.
      Next, as a proof-of-concept application, ABO/Rh blood groups were successfully
      determined through detection of blood antigen-antibody agglutination. The filling
      time of agglutinated samples, driven by the simple syringe-assisted pumping, in
      the dead-end mixing channel was consistently 10% longer than that of blood
      samples without the agglutination reaction. Thus, the proposed device shows great
      potential for use in a wide variety of blood typing assays, agglutination-based
      assays and point-of-care or lab-on-a-chip testing applications.

PMID- 29199734
TI  - Oxidoperoxidomolybdenum(vi) complexes with acylpyrazolonate ligands: synthesis,
      structure and catalytic properties.
AB  - Oxidoperoxido-molybdenum(vi) complexes containing acylpyrazolonate ligands were
      obtained by reaction of [Mo(O)(O)2(H2O)n] with the corresponding acylpyrazolone
      compounds HQR. Complexes Ph4P[Mo(O)(O2)2(QR)] (R = neopentyl, 1; perfluoroethyl,
      2; hexyl, 3; phenyl, 4; naphthyl, 5; methyl, 6; cyclohexyl, 7; ethylcyclopentyl,
      8) were obtained if the reaction was carried out with one equivalent of HQR in
      the presence of Ph4PCl. Alternatively, neutral complexes [Mo(O)(O2)(QR)2] (R =
      neopentyl, 9; hexyl, 10; cyclohexyl, 11) were formed when two equivalents of HQR
      were used in the reaction. These complexes were isolated in good yields as yellow
      or yellow-orange crystalline solids and were spectroscopically (IR, 1H, 13C{1H}
      and 31P{1H} NMR), theoretically (DFT) and structurally characterised (X-ray for
      1, 2, 9 and 10). Compounds 1 and 9 were selected to investigate their catalytic
      behaviour in epoxidation of selected alkenes and oxidation of selected sulphides,
      while 10 and 11 were tested as catalyst precursors in the deoxygenation of
      selected epoxide substrates to alkenes, using PPh3 as the oxygen-acceptor.
      Complexes Ph4P[Mo(O)(O2)2(QR)] were shown to be poor catalyst precursors in
      oxidation reactions, while the activity of [Mo(O)(O2)(QR)2] species is good in
      all the studied reactions and comparable to related oxidoperoxido-molybdenum(vi)
      complexes. Complex [Mo(O)2(QC6)2], 12, was obtained by treatment of 10 with one
      equivalent of PPh3, demonstrating that the first step in the epoxide
      deoxygenation mechanism was the oxygen atom transfer toward the phosphane.

PMID- 29199736
TI  - Pattern formation and self-assembly driven by competing interactions.
AB  - Colloidal fluids interacting via effective potentials which are attractive at the
      short range and repulsive at the long range have long been raising considerable
      attention because such an instance provides a simple mechanism leading to pattern
      formation even for isotropic interactions. If the competition between attraction
      and repulsion is strong enough, the gas-liquid phase transition is suppressed,
      and replaced by the formation of mesophases, i.e., inhomogeneous phases
      displaying periodic density modulations whose length, although being larger than
      the particle size, cannot nevertheless be considered macroscopic. We describe a
      fully numerical implementation of density-functional theory in three dimensions,
      tailored to periodic phases. The results for the equilibrium phase diagram of the
      model are compared with those already obtained in previous investigations for the
      present system as well as for other systems which form mesophases. The phase
      diagram which we find shows a strong similarity with that of block copolymer
      melts, in which self-assembly also results from frustration of a macroscopic
      phase separation. As the inhomogeneous region is swept by increasing the density
      from the low-density side, one encounters clusters, bars, lamellae, inverted
      bars, and inverted clusters. Moreover, a bicontinuous gyroid phase consisting of
      two intertwined percolating networks is predicted in a narrow domain between the
      bar and lamellar phases.

PMID- 29199735
TI  - Ligand-free, palladacycle-facilitated Suzuki coupling of hindered 2
      arylbenzothiazole derivatives yields potent and selective COX-2 inhibitors.
AB  - A similarity search and molecular modeling study suggested the 2'-aryl-2
      arylbenzothiazole framework as a novel scaffold for the design of COX-2-selective
      inhibitors. Conventional Suzuki coupling conditions did not furnish the designed
      compounds in good yield from 2'-bromo-2-arylbenzothiazole as the starting
      material. A novel ligand-free Suzuki-Miyaura coupling methodology was developed
      for sterically hindered 2'-bromo-2-arylbenzothiazoles. The reaction depends on
      the coordination properties of the benzothiazole ring nitrogen, which is involved
      in the formation of a palladacyclic intermediate that was synthesized
      independently and converted to the final product. The new method provides good to
      excellent yields (up to 99%) with favorable functional group tolerability. Six
      compounds had potencies in the submicromolar range against COX-2 and higher
      selectivity for COX-2 vs. COX-1 compared to the currently used drug celecoxib.
      Molecular modeling was used to investigate the possible binding mode with COX-2.

PMID- 29199737
TI  - Fortune teller fermions in two-dimensional materials.
AB  - Dirac-like electronic states are the main engines powering tremendous
      advancements in the research of graphene, topological insulators and other
      materials with these states. Zero effective mass, high carrier mobility and
      numerous applications are some consequences of linear dispersion that
      distinguishes Dirac states. Here we report a new class of linear electronic bands
      in two-dimensional materials with zero electron effective mass and sharp band
      edges, and predict stable materials with such electronic structures utilizing
      symmetry group analysis and an ab initio approach. We make a full classification
      of completely linear bands in two-dimensional materials and find that only two
      classes exist: Dirac fermions on the one hand and fortune teller-like states on
      the other hand. The new class supports zero effective mass similar to that of
      graphene and anisotropic electronic properties like that of phosphorene.

PMID- 29199738
TI  - Metal-free electrophilic phosphination of electron-rich arenes, arenols and
      aromatic thiols with diarylphosphine oxides.
AB  - A new protocol for achieving the phosphination of arenes, arenols and thiols has
      been disclosed. This chemistry, in which
      diaryl(((trifluoromethyl)sulfonyl)oxy)phosphines as a kind of electrophilic
      phosphination reagents are in situ generated from diarylphosphine oxides,
      provides an efficient and mild approach for the synthesis of aromatic
      organophosphorus compounds.

PMID- 29199739
TI  - A Cu(ii)-MOF capable of fixing CO2 from air and showing high capacity H2 and CO2
      adsorption.
AB  - A porous Cu(ii)-MOF shows an adsorption of 6.6 wt% of H2 at 77 K and 62 bar and a
      very high 60 wt% of CO2 at 298 K and 32 bar. When air is bubbled into a
      suspension of the activated MOF in the presence of different epoxides at room
      temperature, the CO2 in air is readily converted into the corresponding cyclic
      carbonates.

PMID- 29199740
TI  - Unprecedented sensitivity towards pressure enabled by graphene foam.
AB  - Reduced graphene oxide foam (RGOF)-based pressure sensors have been fabricated
      through the combination of ultrasonic dispersion and freeze-drying methods. Due
      to the maintenance of the highly disordered structure of the ultrasonic dispersed
      graphene oxides before the freezing process, the RGOF sensors demonstrated an
      ultra-high sensitivity of 22.8 kPa-1, an ultra-low detection limit of around 0.1
      Pa, and a superior separation of 0.2-Pascal-scale difference.

PMID- 29199741
TI  - Surface plasmon-enhanced amplified spontaneous emission from organic single
      crystals by integrating graphene/copper nanoparticle hybrid nanostructures.
AB  - Organic single crystals have attracted great attention because of their
      advantages such as high carrier mobility and high thermal stability. Amplified
      spontaneous emission (ASE) is an important parameter for the optoelectronic
      applications of organic single crystals. Here, surface plasmon-enhanced ASE from
      the organic single crystals has been demonstrated by integrating graphene/copper
      nanoparticle (Cu NP) hybrid nanostructures. Graphene is fully accommodating to
      the topography of Cu NPs by the transfer-free as-grown method for the
      configuration of the hybrid nanostructures, which makes full electrical contact
      and strong interactions between graphene and the local electric field of surface
      plasmon resonances. The enhanced localized surface plasmon resonances induced by
      the hybrid nanostructures result in an enhanced intensity and lowered threshold
      of ASE from the organic single crystals. Moreover, the as-grown graphene sheets
      covering fully and uniformly on the Cu NPs act as a barrier against oxidation,
      and results in an enhanced stability of the fluorescence from the crystals.

PMID- 29199742
TI  - Triangle-, tripod-, and tetrapod-branched ITO nanocrystals for anisotropic
      infrared plasmonics.
AB  - While many sophisticated geometries of metallic nanoparticles have been explored
      for plasmon resonance in the visible light waveband, similar structures for
      infrared plasmonics have seldom been studied. Herein, for the first time, we
      report branched colloidal Sn-doped In2O3 (ITO) NCs prepared through heating metal
      organic precursors in a high boiling solvent and surfactants via a simple one-pot
      method and their interesting anisotropic infrared plasmonics. Shaped ITO NCs were
      anisotropically grown into triangles, tripods, and tetrapods from spherical
      particles by tuning the composition of the surfactants. Interestingly, such
      anisotropic ITO NCs exhibit shape-dependent localized surface plasmon resonances.
      A new peak emerged at a low energy band, and the peak intensity increases when
      the particles become more anisotropic. Meanwhile, a redshift of this newly
      emerging peak and a blueshift of the original peak can also be observed. The
      proposed overlapping spheroid model successfully explained those features and the
      calculated extinction spectra matched excellently with the experimental data.
      Moreover, the origins of those peaks were also revealed and assigned to in-plane
      longitudinal and out-of-plane transverse modes, respectively. This work may help
      design more sophisticated structures for infrared plasmonics and broaden its
      applications in various areas.

PMID- 29199743
TI  - Sensing the impact of environment on small molecule differentiation of RNA
      sequences.
AB  - Using pattern recognition of RNA with small molecules (PRRSM) with fluorescent
      RNA chemosensors and aminoglycosides, we reveal the impact of changing
      environmental conditions on the differentiation of a range of RNA structures as
      well as the ability to predict different sequence/size compositions of five
      canonical RNA motifs.

PMID- 29199744
TI  - Polyaniline and CN-functionalized polyaniline as organic cathodes for lithium and
      sodium ion batteries: a combined molecular dynamics and density functional tight
      binding study in solid state.
AB  - We present the first atomistic-scale simulation of the discharge process of
      polymeric cathode materials for electrochemical batteries in solid state. The
      oxidation of polyaniline (PANI) and of cyano groups (CN) functionalized PANI
      induced by coordination to the electrolyte anions is computed and voltage curves
      are estimated. To deal with the large required numbers of atoms and structures, a
      combination of molecular dynamics and density functional tight binding (DFTB) is
      used. The DFTB is benchmarked to density functional theory (DFT) calculations
      using different functionals to confirm its accuracy. The voltages computed with
      the solid state model are in good agreement with available experimental data and
      ab initio models based on oligomers. The solid state model also predicts
      substantially increased voltage with PANI functionalized with cyano groups.

PMID- 29199745
TI  - Tuning the electronic properties of bilayer group-IV monochalcogenides by
      stacking order, strain and an electric field: a computational study.
AB  - As the isoelectronic counterpart of phosphorene, monolayer group IV-VI binary MX
      (M = Ge, Sn; X = Se, S) compounds have drawn considerable attention in recent
      years. In this paper, we construct four high-symmetry stacking models for bilayer
      MX to tune their electronic properties. We systematically explore the dynamical
      and thermal stabilities of all bilayer MX. It is found that five of them are
      possible at room temperature. Then, we perform first-principles calculations to
      study how the bilayer structure affects their electronic properties. The results
      demonstrate that the electronic properties of MX materials can be modulated by
      forming bilayer structures. Their bandgap can be tuned over a wide range from
      0.789 to 1.617 eV, and an indirect-to-direct transition occurs in three cases.
      Considering the flexibility of bilayer MX, we utilize in-plane uniaxial tensile
      strain to adjust their band structures and achieve much more indirect-to-direct
      bandgap transitions. The realization of direct bandgaps will be helpful for their
      application in next-generation high-efficiency modern nano-optoelectronic and
      photovoltaic devices. We also study the responses of different bilayer MX to an
      external vertical electric field. It is found that their bandgaps decrease
      rapidly with the increase of the electric field.

PMID- 29199746
TI  - Ultrafast interfacial energy transfer and interlayer excitons in the monolayer
      WS2/CsPbBr3 quantum dot heterostructure.
AB  - The idea of fabricating artificial solids with band structures tailored to
      particular applications has long fascinated condensed matter physicists.
      Heterostructure (HS) construction is viewed as an effective and appealing
      approach to engineer novel electronic properties in two dimensional (2D)
      materials. Different from common 2D/2D heterojunctions where energy transfer is
      rarely observed, CsPbBr3 quantum dots (0D-QDs) interfaced with 2D materials have
      become attractive HSs for exploring the physics of charge transfer and energy
      transfer, due to their superior optical properties. In this paper, a new 0D/2D HS
      is proposed and experimentally studied, making it possible to investigate both
      light utilization and energy transfer. Specifically, this HS is constructed
      between monolayer WS2 and CsPbBr3 QDs, and exhibits a hybrid band alignment. The
      dynamics of energy transfer within the investigated 0D/2D HS is characterized by
      femtosecond transient absorption spectrum (TAS) measurements. The TAS results
      reveal that ultrafast energy transfer caused by optical excitation is observed
      from CsPbBr3 QDs to the WS2 layer, which can increase the exciton fluence within
      the WS2 layer up to 69% when compared with pristine ML WS2 under the same
      excitation fluence. Moreover, the formation and dynamics of interlayer excitons
      have also been investigated and confirmed in the HS, with a calculated
      recombination time of 36.6 ps. Finally, the overall phenomenological dynamical
      scenario for the 0D/2D HS is established within the 100 ps time region after
      excitation. The techniques introduced in this work can also be applied to
      versatile optoelectronic devices based on low dimensional materials.

PMID- 29199747
TI  - Postmodification of a supramolecular organic framework: visible-light-induced
      recyclable heterogeneous photocatalysis for the reduction of azides to amines.
AB  - We present the postmodification of a diamondoid 3D supramolecular organic
      framework (SOF) to append [Ru(BPY)3]2+ groups through the formation of a
      hydrazone bond. The resulting SOF works as an efficient recyclable heterogeneous
      catalyst for visible-light-induced reduction of aromatic azides to amines.

PMID- 29199748
TI  - Zwitterionic stealth peptide-protected gold nanoparticles enable long circulation
      without the accelerated blood clearance phenomenon.
AB  - Poly(ethylene glycol) (PEG), which is considered as a gold standard for surface
      modification of nanoparticles in biomedical applications, has been reported to
      encounter the accelerated blood clearance (ABC) phenomenon after repeated
      administration. Herein, as an ideal substitute for PEG, a zwitterionic peptide
      sequence of alternating negatively charged glutamic acid (E) and positively
      charged lysine (K) was designed as a good candidate for surface modification of
      nanoparticles without the ABC phenomenon in vivo. PEG-protected gold
      nanoparticles (AuNP-PEG) suffered from a serious ABC phenomenon with very fast
      blood clearance after repeated injection. Meanwhile, the plasma IgM and IgG
      levels were significantly increased after the repeated injection of AuNP-PEG.
      However, zwitterionic stealth peptide-protected gold nanoparticles (AuNP-EK10)
      could avoid the activation of the ABC phenomenon. The increase of IgM and IgG
      levels was not observed after the repeated injection of AuNP-EK10. More
      interestingly, compared to AuNP-PEG, more AuNP-EK10 could be accumulated in tumor
      tissues after repeated injection of the nanoparticles to tumor-bearing nude mice,
      which might be especially important for the design of drug nanocarriers in cancer
      therapy.

PMID- 29199749
TI  - Non-invasive detection of gastric cancer relevant d-amino acids with luminescent
      DNA/silver nanoclusters.
AB  - Chirality plays essential roles in life systems such that l-amino acids (LAAs)
      are predominantly found as the building units of protein for organisms. The
      presence of the d-enantiomer (DAA) has been found to be specifically relevant to
      gastric cancer. We herein construct a luminescent DNA/silver nanocluster based
      biosensing system to achieve rapid and specific detection of DAAs. As a proof of
      application, we detected DAAs in saliva samples from patients with gastric
      cancer, and the test results exhibited excellent specificity. Our detection
      system has the following major advantages: (i) the detection is rapid, being
      completed in less than 1 hour; (ii) the limit of detection falls in the effective
      range of DAA concentrations of gastric cancer at an early stage, indicating that
      our method is potentially suitable for early diagnosis of gastric cancer; (iii)
      the non-invasive sampling manner provides an adaptable system for point-of-care
      testing (POCT); and (iv) the system does not require any massive instruments or
      expensive reagents, which enables POCT as well.

PMID- 29199750
TI  - High-pressure glass formation of a series of 1-alkyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide homologues.
AB  - We investigated the stability of the liquid phase of a series of 1-alkyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide ([Cnmim][TFSI]) homologues
      with different alkyl chain lengths for 3 <= n <= 10 at room temperature. We found
      that all [Cnmim][TFSI] samples (n = 3-10) formed a glassy state when pressure was
      applied. Intriguingly, the glass transition pressure (pg) slightly increases up
      to n = 5, reaches a plateau at n ? 8, and increases again at n = 10. This is
      completely different from the high-pressure glass formation of [Cnmim][BF4],
      where the pg decreases as n increases. We discussed the local structural changes
      occurring in [Cnmim][TFSI] in view of the conformational changes of the cation
      and anion, and small-angle X-ray scattering data. It seems that [Cnmim][TFSI] is
      resistant to external pressure and retains its local liquid structure by
      conformational adjustments of the cation and anion.

PMID- 29199751
TI  - A closer look into deep eutectic solvents: exploring intermolecular interactions
      using solvatochromic probes.
AB  - Deep eutectic solvents (DESs) constitute a new class of ionic solvents that has
      been developing at a fast pace in recent years. Since these solvents are commonly
      suggested as green alternatives to organic solvents, it is important to
      understand their physical properties. In particular, polarity plays an important
      role in solvation phenomena. In this work, the polarity of different families of
      DESs was studied through solvatochromic responses of UV-vis absorption probes.
      Kamlet-Taft alpha, beta, pi* and ETN parameters were evaluated using different
      solvatochromic probes, as 2,6-dichloro-4-(2,4,6-triphenyl-N-pyridino)-phenolate
      (Reichardt's betaine dye 33), 4-nitroaniline, and N,N-diethyl-4-nitroaniline for
      several families of DESs based on cholinium chloride, dl-menthol and a quaternary
      ammonium salt ([N4444]Cl). In addition, a study to understand the difference in
      polarity properties between DESs and the corresponding ILs, namely ILs based on
      cholinium cation and carboxylic acids as anions ([Ch][Lev], [Ch][Gly] and
      [Ch][Mal]), was carried out. The chemical structure of the hydrogen bond acceptor
      (HBA) in a DES clearly controls the dipolarity/polarizability afforded by the
      DES. Moreover, Kamlet-Taft parameters do not vary much within the family, but
      they differ among families based on different HBA, either for DESs containing
      salts ([Ch]Cl or [N4444]Cl) or neutral compounds (dl-menthol). A substitution of
      the HBD was also found to play an important role in solvatochromic probe
      behaviour for all the studied systems.

PMID- 29199752
TI  - Structure and dynamics of solvent molecules inside the polytheonamide B channel
      in different environments: a molecular dynamics study.
AB  - The beta6.3-helical channel of the marine cytotoxic peptide, polytheonamide B
      (pTB), is examined in water, the POPC bilayer, and a 1 : 1 chloroform/methanol
      mixture using all-atom molecular dynamics simulations. The structures and
      fluctuations of the beta6.3-helix of pTB are investigated in the three
      environments. The average structure of pTB calculated in the mixed solvent is in
      good agreement with the NMR-resolved structure in the mixed solvent, indicating
      the validity of the parameters used for the non-standard groups in pTB. The
      configuration and dynamics of solvent molecules inside the pore are examined in
      detail. It is found that the motions of methanol molecules inside the pore are
      not correlated because of the absence of strong hydrogen bonds (HBs) between
      adjacent methanol molecules. On the other hand, the motions of water molecules
      inside the pore are highly correlated, both translationally and orientationally,
      due to the strong HBs between neighboring water molecules. It is suggested that
      the collective behavior of water molecules inside the pore in the membrane is
      crucial for the permeation of ions through the pTB channel.

PMID- 29199753
TI  - Effects of rhenium dopants on photocarrier dynamics and optical properties of
      monolayer, few-layer, and bulk MoS2.
AB  - We report a comprehensive study on the effects of rhenium doping on optical
      properties and photocarrier dynamics of MoS2 monolayer, few-layer, and bulk
      samples. Monolayer and few-layer samples of Re-doped (0.6%) and undoped MoS2 were
      fabricated by mechanical exfoliation, and were studied by Raman spectroscopy,
      optical absorption, photoluminescence, and time-resolved differential reflection
      measurements. Similar Raman, absorption, and photoluminescence spectra were
      obtained from doped and undoped samples, indicating that the Re doping at this
      level does not significantly alter the lattice and electronic structures. Red
      shift and broadening of the two phonon Raman modes were observed, showing the
      lattice strain and carrier doping induced by Re. The photoluminescence yield of
      the doped monolayer is about 15 times lower than that of the undoped sample,
      while the photocarrier lifetime is about 20 times shorter in the doped monolayer.
      Both observations can be attributed to diffusion-limited Auger nonradiative
      recombination of photocarriers at Re dopants. These results provide useful
      information for developing a doping strategy of MoS2 for optoelectronic
      applications.

PMID- 29199754
TI  - Clustering and dynamics of particles in dispersions with competing interactions:
      theory and simulation.
AB  - Dispersions of particles with short-range attractive and long-range repulsive
      interactions exhibit rich equilibrium microstructures and a complex phase
      behavior. We present theoretical and simulation results for structural and, in
      particular, short-time diffusion properties of a colloidal model system with such
      interactions, both in the dispersed-fluid and equilibrium-cluster phase regions.
      The particle interactions are described by a generalized Lennard-Jones-Yukawa
      pair potential. For the theoretical-analytical description, we apply the hybrid
      Beenakker-Mazur pairwise additivity (BM-PA) scheme. The static structure factor
      input to this scheme is calculated self-consistently using the Zerah-Hansen
      integral equation theory approach. In the simulations, a hybrid simulation method
      is adopted, combing molecular dynamics simulations of colloids with the
      multiparticle collision dynamics approach for the fluid, which fully captures
      hydrodynamic interactions. The comparison of our theoretical and simulation
      results confirms the high accuracy of the BM-PA scheme for dispersed-fluid phase
      systems. For particle attraction strengths exceeding a critical value, our
      simulations yield an equilibrium cluster phase. Calculations of the mean lifetime
      of the appearing clusters and the comparison with the analytical prediction of
      the dissociation time of an isolated particle pair reveal quantitative
      differences pointing to the importance of many-particle hydrodynamic interactions
      for the cluster dynamics. The cluster lifetime in the equilibrium-cluster phase
      increases far stronger with increasing attraction strength than that in the
      dispersed-fluid phase. Moreover, significant changes in the cluster shapes are
      observed in the course of time. Hence, an equilibrium-cluster dispersion cannot
      be treated dynamically as a system of permanent rigid bodies.

PMID- 29199755
TI  - Dynamical properties of heterogeneous nucleation of parallel hard squares.
AB  - We use the Dynamic Density-Functional Formalism and the Fundamental Measure
      Theory as applied to a fluid of parallel hard squares to study the dynamics of
      heterogeneous growth of non-uniform phases with columnar and crystalline
      symmetries. The hard squares are (i) confined between soft repulsive walls with a
      square symmetry, or (ii) exposed to external potentials that mimic the presence
      of obstacles with circular, square, rectangular or triangular symmetries. For the
      first case the final equilibrium profile of a well commensurated cavity consists
      of a crystal phase with highly localized particles in concentric square layers at
      the nodes of a slightly deformed square lattice. We characterize the growth
      dynamics of the crystal phase by quantifying the interlayer and intralayer fluxes
      and the non-monotonicity of the former, the saturation time, and other dynamical
      quantities. The interlayer fluxes are much more monotonic in time, and dominant
      for poorly commensurated cavities, while the opposite is true for well
      commensurated cells: although smaller, the time evolution of interlayer fluxes is
      much more complex, presenting strongly damped oscillations which dramatically
      increase the saturation time. We also study how the geometry of the obstacle
      affects the symmetry of the final equilibrium non-uniform phase (columnar vs.
      crystal). For obstacles with fourfold symmetry, (circular and square) the crystal
      is more stable, while the columnar phase is stabilized for obstacles without this
      symmetry (rectangular or triangular). We find that, in general, density waves of
      columnar symmetry grow from the obstacle. However, additional particle
      localization along the wavefronts gives rise to a crystalline structure which is
      conserved for circular and square obstacles, but destroyed for the other two
      obstacles where columnar symmetry is restored.

PMID- 29199756
TI  - A ferroelectric liquid crystal confined in cylindrical nanopores: reversible
      smectic layer buckling, enhanced light rotation and extremely fast electro
      optically active Goldstone excitations.
AB  - The orientational and translational order of a thermotropic ferroelectric liquid
      crystal (2MBOCBC) imbibed in self-organized, parallel, cylindrical pores with
      radii of 10, 15, or 20 nm in anodic aluminium oxide monoliths (AAO) are explored
      by high-resolution linear and circular optical birefringence as well as neutron
      diffraction texture analysis. The results are compared to experiments on the bulk
      system. The native oxidic pore walls do not provide a stable smectogen wall
      anchoring. By contrast, a polymeric wall grafting enforcing planar molecular
      anchoring results in a thermal-history independent formation of smectic C*
      helices and a reversible chevron-like layer buckling. An enhancement of the
      optical rotatory power by up to one order of magnitude of the confined compared
      to the bulk liquid crystal is traced to the pretransitional formation of helical
      structures at the smectic-A*-to-smectic-C* transformation. A linear electro
      optical birefringence effect evidences collective fluctuations in the molecular
      tilt vector direction along the confined helical superstructures, i.e. the
      Goldstone phason excitations typical of the para-to-ferroelectric transition.
      Their relaxation frequencies increase with the square of the inverse pore radii
      as characteristic of plane-wave excitations and are two orders of magnitude
      larger than in the bulk, evidencing an exceptionally fast electro-optical
      functionality of the liquid-crystalline-AAO nanohybrids.

PMID- 29199757
TI  - Visible light driven plasmonic photochemistry on nano-textured silver.
AB  - Plasmon assisted generation of silver sulfate from dodecanethiol is demonstrated
      on a nano-textured silver substrate with a strong surface plasmon resonance in
      the visible range. The observed photo-physical processes are attributed to hot
      charge carriers that are generated from the excitation of surface plasmon
      resonances using 532 nm laser light. Excited charge carriers are responsible for
      cleaving the alkane chain, and for generating reactive oxygen species which
      rapidly photooxidize the exposed sulfur atoms. The ability to drive photochemical
      reactions with photon energies in the visible range rather than in the UV, on
      nano-textured silver surfaces, will enable researchers to study photochemical
      transformations for a wide variety of applications. The strong optical absorbance
      across the visible range, combined with the fact that the substrates can be
      fabricated over large areas, naturally makes them candidates for solar driven
      photochemical applications, and for large scale plasmonic reactors.

PMID- 29199758
TI  - Reversible generation of coacervate droplets in an enzymatic network.
AB  - Cells can control the assembly and disassembly of membraneless organelles by
      enzymatic processes, but similar control has not been achieved in vitro yet. Here
      we develop ATP-based coacervate droplets as artificial membraneless organelles
      that can be fully controlled by two cooperating enzymes. Droplets can be
      generated within a minute following the addition of phosphoenolpyruvate as a
      substrate, and they can be dissolved within tens of seconds by adding glucose as
      the second substrate. We show how the rates of droplet generation and dissolution
      can be tuned by varying the enzyme and substrate concentrations, and we support
      our findings with a kinetic model of the underlying enzymatic reaction network.
      As all steps of the coacervate droplet life cycle, including nucleation,
      coarsening, and dissolution, occur under the same reaction conditions, the cycle
      can be repeated multiple times. In addition, by carefully balancing the rates of
      both enzymatic reactions, our system can be programmed to either form or dissolve
      droplets at specified times, acting as a chemical timer.

PMID- 29199759
TI  - XANES study of vanadium and nitrogen dopants in photocatalytic TiO2 thin films.
AB  - We report an X-ray absorption near edge structure (XANES) study of vanadium (V)
      and nitrogen (N) dopants in anatase TiO2 thin films deposited by radio-frequency
      magnetron sputtering. Measurements at the Ti K and V K edges were combined with
      soft X-ray experiments at the Ti L2,3, O K and N K edges. Full potential ab
      initio spectral simulations of the V, O and N K-edges were carried out for
      different possible configurations of substitutional and interstitial dopant
      related point defects in the anatase structure. The comparison between
      experiments and simulations demonstrates that V occupies substitutional cationic
      sites (replacing Ti) irrespective of the film structure and dopant concentration
      (up to 4.5 at%). On the other hand, N is found both in substitutional anionic
      sites (replacing O) and as N2 dimers within TiO2 interstices. The dopants' local
      structures are discussed with reference to the enhanced optical absorption and
      photocatalytic activity achieved by (co)doping.

PMID- 29199760
TI  - Effectivity and Cost-effectivity of the Maintenance Electroconvulsive Therapy: A
      mirror naturalistic analysis.
AB  - INTRODUCTION: Maintenance Electroconvulsive Therapy (mECT) is a biological long
      term treatment in which patients receive ECT on periods from 2 to 4 weeks, during
      a variable period of time, usually for more than 6 months. Recent studies showed
      the efficacy of mECT in prevention of relapse and recurrences. Our study wants to
      demostrate the effectivity and cost-effectivity of this therapy in the
      naturalistic conditions of our area. METHODOLOGY:  DESIGN: Retrospective
      longitudinal study, with mirror analysis in naturalistic conditions. SUBJECTS:
      Patients attended at the Corporacio Sanitaria Parc Tauli (Sabadell, Catalonia),
      and included in the mECT program during more than six months. We performed
      diagnostic following DSM-IV criteria, subdividing the sample in three groups:
      patients affected of Recurrent Major Depression, Bipolar Disorder and
      Schizophrenia and Related Disorders. MEASURES: Number and duration of
      hospitalizations for the previous three years before the beginning of mECT,
      compared with the same data for the next three years following the beginning of
      mECT. Comparative analysis of direct hospitalization costs, costs of the mECT and
      pharmacologic costs. Statistic: Descriptive and non- parametric tests. RESULTS:
      Sample of 35 patients (1997-2008). There is a significative reduction the number
      of hospitalizations and days of hospitalization in the total sample and also in
      each of the three subgroups. The direct total cost decreased but it was only
      significant in the Bipolar Disorder subgroup, due to the increased
      pharmacological costs. CONCLUSIONS: mECT in our area is an effective and
      costeffective treatment with a great impact on the reduction of clinical decline
      and hospitalizations.

PMID- 29199761
TI  - Difference in Regional Brain Volume between Fibromyalgia Patients and Long-Term
      Meditators.
AB  - BACKGROUND: The practice of meditation has been shown to improve pain-related
      quality of life and also to alter brain activity. To assess brain volumetry in
      fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control
      groups, and to elucidate the possible association between brain changes in
      meditators and years of meditation practice. METHODS: Twelve patients diagnosed
      with FM, eleven long-term Zen meditators and ten healthy control subjects closely
      matched for sex and age were recruited. A high resolution T1-3D sequence was
      acquired and a high-dimensional DARTEL normalization strategy was applied.
      Questionnaires on anxiety, depression and cognitive impairment were administered.
      RESULTS: There was a statistically significant increase in grey matter volume in
      the Brodmann area 20 (right and left inferior temporal gyri) in patients with
      fibromyalgia and a significant decrease in the meditator group as compared to
      controls. On the other hand, there was a significant increase in grey matter
      volume in fibromyalgia patients as compared to controls and meditators, to the
      right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31).
      The number of months of meditation did not correlate with significant grey matter
      volume changes in the meditator group. CONCLUSIONS: FM and meditation appears to
      be reliably associated with altered anatomical structure in the Brodmann area 20
      (in both inferior temporal gyri), and these changes are associated with anxiety
      and depression levels. In addition, exploratory morphometric analyses for
      fibromyalgia patients and meditators may reveal relevant brain regions showing
      structural diminution in meditation practitioners. Morphologic changes might
      predispose toward vulnerability to develop a chronic pain state. Such structural
      diminutions could potentially indicate functional benefits.

PMID- 29199762
TI  - m-RESIST, a complete m-Health solution for patients with treatmentresistant
      schizophrenia: a qualitative study of user needs and acceptability in the
      Barcelona metropolitan area.
AB  - BACKGROUND: Despite the theoretical potential of m-health solutions in the
      treatment of patients with schizophrenia, there remains a lack of technological
      solutions in daily practice. The aim of this study was to measure the receptivity
      of patients, informal carers, and clinicians to an integral intervention model
      focused on patients with persistent positive symptoms: Mobile Therapeutic
      Attention for Patients with Treatment Resistant Schizophrenia (m-RESIST).
      METHODS: A qualitative study of the needs and acceptability of outpatients with
      treatment-resistant schizophrenia was carried out in Parc Sanitari Sant Joan de
      Deu (Barcelona). We analyzed the opinions of patients, informal carers, and
      clinicians concerning the services initially thought to be part of the solution.
      Five focus groups and eight interviews were carried out, using discourse analysis
      as the analytical approach. RESULTS: A webpage and a virtual forum were perceived
      as suitable to get reliable information on both the disease and support. Data
      transmission service, online visits, and instant messages were evaluated as ways
      to improve contact with clinicians. Alerts were appreciated as reminders of daily
      tasks and medical appointments. Avoiding stressful situations for outpatients,
      promoting an active role in the management of the disease, and maintaining human
      contact with clinicians were the main suggestions for improving the effectiveness
      of the solution. CONCLUSIONS: Positive acceptance of m-RESIST services is related
      to its usefulness in meeting user needs, its capacity to empower them, and the
      possibility of maintaining human contact.

PMID- 29199763
TI  - Domiciliary intervention in psychosis: a systematic review.
AB  - BACKGROUND: This theoretical study reviews the main findings and research on home
      based treatment for psychosis. The principal purpose was to analyze the various
      types of home-based service and make recommendations for a service that would
      meet the needs of both first-episode and resistant patients. We compare the Early
      Intervention Service, which aims to reduce the range of untreated psychosis (DUP)
      with other types of home-care and similar interventions that have already been
      implemented: crisis resolution home teams (CRHTs), Open Dialogue Approach (ODA),
      social skills training (SST) and foster homes. METHOD: We searched electronic
      bibliographic databases including PubMed, PsycINFO, and Discovery for relevant
      publications appearing between 2005 and 2015. Ninetythree publications were
      deemed eligible for inclusion; 9 of these were systematic reviews and the rest
      were scientific papers or books. DISCUSSION: We describe in this review the most
      widely used home-based interventions, including individual and family therapy.
      Multidisciplinary teams carry out all the interventions discussed. There does not
      appear to be a form of psychotherapy, which is effective in treating resistant
      patients. CONCLUSIONS: Home-based interventions improve adherence to treatment,
      everyday living and social skills and also have a beneficial impact on family
      conflicts and other social conflicts. As a whole result, the number of incomes is
      reduced, patients&#8217; quality of life and autonomy are increased and inclusion
      and community living are improved.

PMID- 29199765
TI  - Application of stem cells to the knowledge and treatment of psychiatric diseases.

PMID- 29199764
TI  - Pharmacogenetics in psychiatry: Clinical case of resistant depression and a
      previous history of multiple adverse effects.

PMID- 29199766
TI  - Pentasaccharides for the treatment of deep vein thrombosis.
AB  - BACKGROUND: Standard treatment of deep vein thrombosis (DVT) is based on
      antithrombotic therapy, initially with parenteral administration of
      unfractionated heparin or low molecular weight heparins (LMWH) for five to seven
      days, then subsequent long-term therapy with oral vitamin K antagonists (e.g.
      warfarin). Pentasaccharides are novel anticoagulants that may be favourable over
      standard therapy due to their predictable effect, no need for frequent monitoring
      or re-dosing, and few known drug interactions. Heparin-induced thrombocytopenia,
      a harmful effect of heparins, appears to be rare during treatment with
      pentasaccharides. OBJECTIVES: To assess the efficacy and harms of
      pentasaccharides for the treatment of deep vein thrombosis. SEARCH METHODS: The
      Cochrane Vascular Information Specialist (CIS) searched the Specialised Register
      (22 March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL)
      (2017, Issue 2) (searched 22 March 2017). We searched clinical trials databases
      for details of ongoing or unpublished studies and the reference lists of relevant
      articles for additional citations. SELECTION CRITERIA: We included randomised
      controlled trials in which people 18 years of age or older with a DVT confirmed
      by standard imaging techniques were allocated to receive a pentasaccharide
      (fondaparinux, idraparinux, or idrabiotaparinux) for the treatment of DVT in
      comparison with standard therapy or other treatments. DATA COLLECTION AND
      ANALYSIS: We extracted data characterising the included trials according to the
      methods, participants, interventions, and outcomes. We assessed risk of bias
      using Cochrane's 'Risk of bias' tool and employed the GRADE methodology to
      evaluate the quality of the evidence.The main primary outcome for efficacy was
      recurrent venous thromboembolism (VTE), and the main primary outcome for harm was
      major and clinically relevant bleeding. Since our outcomes were dichotomous, we
      calculated the risk ratio (RR) with a 95% confidence interval (CI). We combined
      the effects of different comparisons through a meta-analysis using a fixed-effect
      model. MAIN RESULTS: We included five randomised controlled trials of 6981
      participants comparing pentasaccharides with standard therapy or other
      pentasaccharides. The quality of the evidence varied depending on the outcome and
      was judged as of moderate to very low quality. We downgraded the quality of the
      evidence due to risk of bias or imprecision, or both.Two studies evaluated
      fondaparinux, at doses of 5.0 mg, 7.5 mg, and 10.0 mg, plus vitamin K antagonist
      in comparison with standard therapy. A meta-analysis of these two studies showed
      no clear difference in the risk of recurrent VTE (RR 0.80, 95% CI 0.43 to 1.47;
      2658 participants); moderate-quality evidence. The frequencies of major bleeding
      were similar between interventions in the initial period of treatment
      (approximately five days) (RR 1.15, 95% CI 0.39 to 3.44; 2645 participants) and
      at three months' follow-up (RR 1.05, 95% CI 0.64 to 1.71; 2645 participants). We
      judged the quality of the evidence as moderate.One study (757 participants)
      compared idrabiotaparinux (3.0 mg) with idraparinux (2.5 mg) and demonstrated no
      clear difference in the risk of recurrent VTE at six months' follow-up (RR 0.72,
      95% CI 0.31 to 1.69); low-quality evidence. Major bleeding during the initial
      treatment period was not reported. Major bleeding at six-month follow-up was less
      frequent in participants receiving idrabiotaparinux versus participants treated
      with idraparinux (RR 0.21, 95% CI 0.06 to 0.71); low-quality evidence.The effect
      of an initial treatment with LMWH followed by three months of idraparinux (10 mg)
      showed no clear difference from standard therapy for risk of recurrent VTE (RR
      1.51, 95% CI 0.26 to 8.90; 263 participants); very low-quality evidence; one
      study. Major bleeding during the initial treatment period was not reported. The
      frequency of major and other clinically relevant bleeding at three months' follow
      up ranged from 2% to 15% in participants receiving LMWH and increasing doses of
      idraparinux of 2.5 mg, 5 mg, 7.5 mg, or 10 mg. When dosage groups were combined,
      there was no clear difference in major plus other clinically relevant bleeding or
      in major bleeding alone between the idraparinux treatment group and the standard
      therapy group (RR 1.30, 95% CI 0.70 to 2.40; 659 participants; RR 3.76, 95% CI
      0.50 to 28.19; 659 participants, respectively); very low-quality evidence.One
      study (2904 participants) compared idraparinux (2.5 mg) to standard therapy.
      There was no clear difference in the risk of recurrent VTE at three months'
      follow-up (RR 0.98, 95% CI 0.64 to 1.48); low-quality evidence. Major bleeding
      during the initial treatment period was not reported. Major bleeding at three
      months of follow-up appeared to be similar in the idraparinux group and the
      standard therapy group (RR 0.71, 95% CI 0.34 to 1.47); very low-quality evidence.
      AUTHORS' CONCLUSIONS: We found moderate-quality evidence that the effects of
      fondaparinux at doses of 5.0 mg, 7.5 mg, and 10.0 mg plus vitamin K antagonist
      are similar in terms of recurrent VTE and risk of major bleeding compared with
      standard treatment for DVT.Low-quality evidence suggests equal efficacy of
      idraparinux at 2.5 mg and the equimolar dose of 3.0 mg of idrabiotaparinux with
      regard to recurrent VTE, but a higher frequency of major bleeding was observed in
      participants treated with idraparinux.We judged evidence on the effectiveness of
      idraparinux compared with standard therapy, with or without initial treatment
      with LMWH, and on associated bleeding risk to be low to very low quality,
      therefore we have very limited confidence in the estimated effects.The observed
      similar effectiveness in terms of recurrent DVT and harmful effects in terms of
      bleeding risk with fondaparinux plus vitamin K antagonist compared to standard
      treatment for DVT suggest that it may be an alternative to conventional
      anticoagulants for the treatment of DVT in certain circumstances.

PMID- 29199767
TI  - Oxcarbazepine for neuropathic pain.
AB  - BACKGROUND: Several anticonvulsant drugs are used in the management of
      neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to
      carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment
      of neuropathic pain, but evidence from randomised controlled trials (RCTs) is
      conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine.
      This is the first update of a review published in 2013. OBJECTIVES: To assess the
      benefits and harms of oxcarbazepine for different types of neuropathic pain.
      SEARCH METHODS: On 21 November 2016, we searched the Cochrane Neuromuscular
      Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese
      Biomedical Retrieval System (January 1978 to November 2016). We searched the US
      National Institutes of Health (NIH) databases and the World Health Organization
      (WHO) International Clinical Trials Registry Platform for ongoing trials in
      January 2017, and we wrote to the companies who make oxcarbazepine and to pain
      experts requesting additional information. SELECTION CRITERIA: All RCTs and
      randomised cross-over studies of oxcarbazepine for the treatment of people of any
      age or sex with any neuropathic pain were eligible. We planned to include trials
      of oxcarbazepine compared with placebo or any other intervention with a treatment
      duration of at least six weeks, regardless of administration route and dose. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
      Cochrane. MAIN RESULTS: Five multicentre, randomised, placebo-controlled, double
      blind trials with a total of 862 participants were eligible for inclusion in this
      updated review. Three trials involved participants with painful diabetic
      peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain
      due to radiculopathy (n = 145), and one, which was newly identified at this
      update, involved participants with peripheral neuropathic pain of mixed origin
      (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83).
      Some studies did not report all outcomes of interest. For painful DPN, compared
      to the baseline, the proportion of participants who reported at least a 50% or
      30% reduction of pain scores after 16 weeks of treatment in the oxcarbazepine
      group versus the placebo group were: at least 50% reduction: 34.8% with
      oxcarbazepine versus 18.2% with placebo (risk ratio (RR) 1.91, 95% confidence
      interval (CI) 1.08 to 3.39, number of people needed to treat for an additional
      beneficial outcome (NNTB) 6, 95% CI 3 to 41); and at least 30% reduction: 44.9%
      with oxcarbazepine versus 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB
      6, 95% CI 3 to 114; n = 146). Both results were based on data from a single
      trial, since two trials that found little or no benefit did not provide data that
      could be included in a meta-analysis. Although these trials were well designed,
      incomplete outcome data and possible unblinding of participants due to obvious
      adverse effects placed the results at a high risk of bias. There was also serious
      imprecision and a high risk of publication bias. The radiculopathy trial reported
      no benefit for the outcome 'at least 50% pain relief' from oxcarbazepine. In
      mixed neuropathies, 19.3% of people receiving oxcarbazepine versus 4.8% receiving
      placebo had at least 50% pain relief. These small trials had low event rates and
      provided, at best, low-quality evidence for any outcome. The proportion of people
      with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine versus
      30.1% with placebo in DPN (RR 1.46, 95% CI 1.13 to 1.88; n = 493; 2 trials; very
      low-quality evidence) and 23.9% with oxcarbazepine versus 14.9% with placebo in
      radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145).We found no trials in other
      types of neuropathic pain such as trigeminal neuralgia.Trial reports stated that
      most adverse effects were mild to moderate in severity. Based on moderate-quality
      evidence from the three DPN trials, serious adverse effects occurred in 8.3% with
      oxcarbazepine and 2.5% with placebo (RR 3.65, 95% CI 1.45 to 9.20; n = 634;
      moderate-quality evidence). The number needed to treat for an additional harmful
      (serious adverse effect) outcome (NNTH) was 17 (95% CI 11 to 42). The RR for
      serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to
      14.98, n = 145). The fifth trial did not provide data.More people withdrew
      because of adverse effects with oxcarbazepine than with placebo (DPN: 25.6% with
      oxcarbazepine versus 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40;
      radiculopathy: 42.3% with oxcarbazepine versus 14.9% with placebo; RR 2.84, 95%
      CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine versus 1.2%
      with placebo; RR 11.51, 95% CI 1.54 to 86.15). AUTHORS' CONCLUSIONS: This review
      found little evidence to support the effectiveness of oxcarbazepine in painful
      diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of
      neuropathies. Some very-low-quality evidence suggests efficacy but small trials,
      low event rates, heterogeneity in some measures and a high risk of publication
      bias means that we have very low confidence in the measures of effect. Adverse
      effects, serious adverse effects and adverse effects leading to discontinuation
      are probably more common with oxcarbazepine than placebo; however, the numbers of
      participants and event rates are low. More well-designed, multicentre RCTs
      investigating oxcarbazepine for various types of neuropathic pain are needed, and
      selective publication of studies or data should be avoided.

PMID- 29199768
TI  - Invasive versus non-invasive ventilation for acute respiratory failure in
      neuromuscular disease and chest wall disorders.
AB  - BACKGROUND: Acute respiratory failure is a common life-threatening complication
      of acute onset neuromuscular diseases, and may exacerbate chronic hypoventilation
      in patients with neuromuscular disease or chest wall disorders. Standard
      management includes oxygen supplementation, physiotherapy, cough assistance, and,
      whenever needed, antibiotics and intermittent positive pressure ventilation. Non
      invasive mechanical ventilation (NIV) via nasal, buccal or full-face devices has
      become routine practice in many centres. OBJECTIVES: The primary objective of
      this review was to compare the efficacy of non-invasive ventilation with invasive
      ventilation in improving short-term survival in acute respiratory failure in
      people with neuromuscular disease and chest wall disorders. The secondary
      objectives were to compare the effects of NIV with those of invasive mechanical
      ventilation on improvement in arterial blood gas after 24 hours and lung function
      measurements after one month, incidence of barotrauma and ventilator-associated
      pneumonia, duration of mechanical ventilation, length of stay in the intensive
      care unit and length of hospital stay. SEARCH METHODS: We searched the following
      databases on 11 September 2017: the Cochrane Neuromuscular Specialised Register,
      CENTRAL, MEDLINE and Embase. We also searched conference proceedings and clinical
      trials registries. SELECTION CRITERIA: We planned to include randomised or quasi
      randomised trials with or without blinding. We planned to include trials
      performed in children or adults with acute onset neuromuscular diseases or
      chronic neuromuscular disease or chest wall disorders presenting with acute
      respiratory failure that compared the benefits and risks of invasive ventilation
      versus NIV. DATA COLLECTION AND ANALYSIS: Two review authors reviewed searches
      and independently selected studies for assessment. We planned to follow standard
      Cochrane methodology for data collection and analysis. MAIN RESULTS: We did not
      identify any trials eligible for inclusion in the review. AUTHORS' CONCLUSIONS:
      Acute respiratory failure is a life-threatening complication of acute onset
      neuromuscular disease and of chronic neuromuscular disease and chest wall
      disorders. We found no randomised trials on which to elaborate evidence-based
      practice for the use of non-invasive versus invasive mechanical ventilation. For
      researchers, there is a need to design and conduct new randomised trials to
      compare NIV with invasive ventilation in acute neuromuscular respiratory failure.
      These trials should anticipate variations in treatment responses according to
      disease condition (acute onset versus acute exacerbation on chronic neuromuscular
      diseases) and according to the presence or absence of bulbar dysfunction.

PMID- 29199769
TI  - Peritoneal dialysis for acute kidney injury.
AB  - BACKGROUND: Peritoneal dialysis (PD) has been suggested as an effective and safe
      dialysis modality in patients with acute kidney injury (AKI). However, whether PD
      is superior to extracorporeal therapy (e.g. haemodialysis) in terms of improving
      survival, recovery of kidney function, metabolic and clinical outcomes is still
      inconclusive. OBJECTIVES: The aim of this review was to evaluate the benefits and
      harms of PD for patients with AKI compared with extracorporeal therapy or
      different PD modalities. SEARCH METHODS: We searched the Cochrane Kidney and
      Transplant Register of Studies to 29 May 2017 through contact with the
      Information Specialist using search terms relevant to this review. Studies in the
      Register are identified through searches of CENTRAL, MEDLINE, and EMBASE,
      conference proceedings, the International Clinical Trials Register (ICTRP) Search
      Portal, and ClinicalTrials.gov. We also searched the China Biological Medicine
      Database. SELECTION CRITERIA: We included patients with AKI who were randomised
      to receive PD, extracorporeal therapy, or different PD modalities regardless of
      their age, sex, primary disease and clinical course. DATA COLLECTION AND
      ANALYSIS: Screening, selection, data extraction and quality assessments for each
      retrieved article were carried out by two authors using standardised forms.
      Authors contacted when published data were incomplete. Statistical analyses were
      performed using the random effects model and results expressed as risk ratio (RR)
      with 95% confidence intervals (CI). Heterogeneity among studies was explored
      using the Cochran Q statistic and the I2 test. Outcomes of interest included all
      cause mortality, recovery of kidney function, weekly delivered Kt/V, correction
      of acidosis, fluid removal, duration of dialysis, and infectious complications.
      Confidence in the evidence was assessing using GRADE. MAIN RESULTS: Six studies
      (484 participants) met our inclusion criteria. Five studies compared high volume
      PD with daily haemodialysis, extended daily haemodialysis, or continuous renal
      replacement therapy. One study focused on the intensity of PD. The overall risk
      of bias was low to unclear. Compared to extracorporeal therapy, PD probably made
      little or no difference to all-cause mortality (4 studies, 383 participants: RR
      1.12, 95% CI 0.81 to 1.55; I2 = 69%; moderate certainty evidence), or kidney
      function recovery (3 studies, 333 participants: RR 0.95, 95% CI 0.68 to 1.35; I2
      = 0%; moderate certainty evidence). PD probably slightly reduces the amount of
      fluid removal compared to extracorporeal therapy (3 studies, 313 participants: MD
      -0.59 L/d, 95% CI -1.19 to 0.01; I2 = 89%; low certainty evidence), and probably
      made little or no difference to infectious complications (2 studies, 263
      participants: RR 1.03, 95% CI 0.60 to 1.78; I2 = 0%; low certainty evidence). It
      is uncertain whether PD compared to extracorporeal therapy has any effects on
      weekly delivered Kt/V (2 studies, 263 participants: MD -2.47, 95% CI -5.17 to
      0.22; I2 = 99%; very low certainty evidence), correction of acidosis (2 studies,
      89 participants: RR 1.32, 95% CI 0.13 to 13.60; I2 = 96%; very low certainty
      evidence), or duration of dialysis (2 studies, 170 participants: MD -1.01 hours,
      95% CI -91.49 to 89.47; I2 = 98%; very low certainty evidence). Heterogeneity was
      high and this may be due to the different extracorporeal therapies used.One study
      (61 participants) reported little or no difference to all-cause mortality, kidney
      function recovery, or infection between low and high and intensity PD. Weekly
      delivered Kt/V and fluid removal was lower with low compared to high intensity
      PD. AUTHORS' CONCLUSIONS: Based on moderate (mortality, recovery of kidney
      function), low (infectious complications), or very low certainty evidence
      (correction of acidosis) there is probably little or no difference between PD and
      extracorporeal therapy for treating AKI. Fluid removal (low certainty) and weekly
      delivered Kt/V (very low certainty) may be higher with extracorporeal therapy.

PMID- 29199770
TI  - The organ transplanted patient in the dental clinic

PMID- 29199771
TI  - Cling film as storage medium for avulsed teeth. An in vitro pilot study
AB  - The long-term prognosis of avulsed teeth primarily depends on the behavior at the
      scene of the accident. Lay people are not able to perform an immediate
      replantation. Therefore, particular significance belongs to the cellphysiologic
      storage of avulsed teeth. The aim of this pilot study was to evaluate whether
      cling film facilitates the survival of periodontal ligament cells in vitro. For
      this purpose, healthy human third molars were used. They were cut into root
      slices, which were stored in one of five test media: SOS Zahnbox (r) , UHT milk
      (4  degrees C), sterile isotonic saline solution, tap water, and cling film.
      Following storage periods of 2 hours, 6 hours, and 24 hours in the respective
      medium, slices were cultivated at 37  degrees C and 5% CO 2 . After 2 days, 7
      days, and 14 days in culture, surviving periodontal ligament cells of each slice
      were assessed quantitatively. Apart from tap water, all investigated media
      promoted cell survival. At the time of 2 hours, storage in cling film facilitated
      the highest cell growth compared to all other media. At the time of 6 hours,
      teeth stored in cling film sho wed cell growth comparable to that observed in the
      SOS Zahnbox (r). The results of this pilot study indicate that cling film
      possibly could be used as an alternative transport medium for a storage period of
      up to 6 hours.

PMID- 29199772
TI  - [Not Available].

PMID- 29199773
TI  - ?

PMID- 29199774
TI  - [Not Available].

PMID- 29199775
TI  - [Not Available].

PMID- 29199776
TI  - The organ transplanted patient in the dental clinic

PMID- 29199777
TI  - Current follow-up of a breast cancer patient.
AB  - The number of patients with breast cancer is on the rise, which leads to an
      increasing number of patients in need of follow-up and support for recovery from
      treatments. The disease will recur in one out of five patients. With the
      exception of imaging of the breasts carried out at intervals of 1 to 2 years,
      frequent appointments or imaging have not been shown to be beneficial for the
      prognosis. Follow-up care of breast cancer is well suited to be carried out by
      the nursing staff. The status of mobile applications developed for patient
      monitoring as part of the surveillance is becoming more clear.

PMID- 29199778
TI  - Influence of ethnicity on vertical jump performances in male physical education
      students: a pilot study.
AB  - BACKGROUND: The present study aimed to: i) test the possibility of ethnic
      differences in squat jump (SJ), countermovement jump (CMJ) and countermovement
      jump with arms swing (CMJA); ii) test the possibility of ethnic differences in
      the effects of countermovement and arms swing; iii) verify whether the
      relationships between the different vertical jumps VJ (SJ, CMJ, CMJA) and maximal
      power (Pmax), determined from a force-velocity test (F-V), were dependent on the
      ethnicity as previously found for CMJA. METHODS: VJ were performed by 84 active
      men (WAC): 40 WA and 44 C. VJ were measured on a force platform in three
      conditions: SJ, CMJ and CMJA. For technical reasons, only 39 of these
      participants (WA2C2) performed F-V test [V=V0(1-F/F0) and maximal power=0.25
      V0F0]: 20 WA (WA2) and 19 C (C2). RESULTS: There were significant ethnic
      differences (WA > C) in SJ, CMJ, CMJA, CMJA-CMJ, CMJA/CMJ. The effect sizes
      (Cohen d) of these ethnic differences were large for CMJA (0.93), CMJA-CMJ (1.11)
      CMJA/CMJ (0.82) and medium for CMJ (0.54) and SJ (0.56). Ethnic effect in the
      countermovement jump was small (Cohen d=0.04 for CMJ-SJ) and not significant.
      CONCLUSIONS: For WA2C2, the slightly higher value of Pmax in WA2 (Cohen d =0.23)
      probably explained their slightly higher values of SJ, CMJ but not their higher
      values of CMJA and arms swing effect. In WA2C2, a difference in fast-fibre
      percentages was not the explanation of the ethnic differences because the optimal
      pedal rates corresponding to Pmax (0.5 V0) were similar in both groups.

PMID- 29199779
TI  - Analysis of muscular activity in archery: a comparison of skill level.
AB  - AIM: A series of archery shooting movements requires strong activity of muscles
      attached to the shoulder girdle and upper extremity. It is unclear which muscles
      influence archery competition scores. This study aimed to compare muscle activity
      of the shoulder girdle and upper extremity during shooting movements and to
      analyze the muscles influencing in archeryskill improvement. METHODS: Thirty male
      archers, who were divided into three groups based on skill level (elite,
      preelite, and beginner), were included in this study. The angle of shoulder joint
      abduction, horizontal extension, and elbow joint flexion, as well as the
      electromyographic activity of the upper trapezius, lower trapezius, deltoid
      middle, deltoid posterior, biceps brachii, and triceps brachii muscles at the
      point of stabilization during shooting, were measured. RESULTS: In the elite
      group, the activity of the lower trapezius muscle was significantly higher (P <
      0.05), while that of the biceps brachii and triceps brachii muscles were
      significantly lower (P < 0.05) compared to the preelite and beginner groups.
      CONCLUSIONS: The lower trapezius muscle of the draw arm is actively involved in
      scapular fixation during shooting. Therefore, in order to improve the archery
      competition score, training focused on the lower trapezius muscle is necessary.

PMID- 29199780
TI  - Effects of increased training volume during a 10 day training camp on competitive
      performance in national level youth swimmers.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of increased
      training volume during a 10 day training camp on competitive performance and
      internal training load (ITL). In addition, coach and swimmer rating of perceived
      exertion (RPE) for each session was compared. METHODS: Ten national level
      swimmers (Gender: 4 males and 6 females; age: 15+/-1 years; height: 170.5+/-6.4
      cm; body mass: 61.4+/-7.4 kg) participated in the training camp which involved a
      36% increase in swimming volume. Competitive performance, as assessed using the
      FPS (FINA points system), was recorded pre and post-camp. Internal training load
      was recorded using the Session-RPE method and RESTQ-52 Sport questionnaire for
      each session and for day 1, 5 and 10 of the camp, respectively. Coach RPE was
      recorded after each training session for coach-swimmer RPE comparisons. RESULTS:
      Competitive performance increased by 7.1% from pre-camp to post-camp (P=0.001,
      dz=1.6). Session-RPE increased between day 1 and all other days of the training
      camp (P<0.05), except day 6 (P=0.221). The injury scale of the RESTQ
      questionnaire increased from day 1 to day 5 (P=0.022). Across 16 swimming
      sessions, there was a strong correlation between coach and swimmer RPE (rs=0.76)
      however RPE was found to be higher for the swimmers than the coach (P=< 0.0005)
      during moderate training sessions. CONCLUSIONS: These findings suggest that a 36%
      increase in swimming volume during a 10 day training camp resulted in significant
      changes to competitive performance and ITL. However, coach and swimmer RPE should
      be monitored closely during future camps.

PMID- 29199781
TI  - Velocity distribution of women's 30-km cross-country skiing during Olympic Games
      from 2002-2014.
AB  - BACKGROUND: Within several investigated endurance sport disciplines the
      distribution of load of the best competitors has a manner of evenly or slightly
      rising velocity values. Unfortunately many other competitors have usually
      diminishing values or when they are very poor they have evenly values. The aim of
      this study was to investigate distribution of velocity within 30-km cross-country
      female skiers. METHODS: Cross-country skiing runs were investigated of Olympic
      Games 2002-2014 (Salt Lake City, Turin, Vancouver, Sochi). At every race two 15
      km or three 10 km loops of the same vertical profile were taken into account. The
      competitors were divided onto: A - winners, B - medallists, C - competitors who
      obtained places 4 to 10 at the finish line (medium runners), D - competitors who
      obtained places 11 to 30 at the finish line (poor runners). Velocity data
      presented on the web pages of several institutions were utilized. RESULTS: The
      competitors had their velocity distributed in a manner with usually diminishing
      values. While comparing velocity of sequential loops with the mean velocity the
      difference for the poor runners reached the value of almost 6 %, which was too
      high. There was significant (usually negative) correlation coefficient between
      values of velocity deviation for the first and second loops and the mean value of
      velocity for the entire distance for the better runners and mixed, i.e. positive
      and negative values for the poorer runners. CONCLUSIONS: It was postulated
      investigations of velocity distribution should be introduced in coaching in order
      to inform competitors about their running. This advise is especially important
      for the poorer runners. Up to now cross country skiers run for themselves. It
      should be discussed whether the tactics used by road and track runners, i.e.
      running with pace makers, can be introduced in cross country skiing. Also the use
      of a drone during training can be used in order to maintain proper pace.

PMID- 29199782
TI  - Anthropometric and physiological characteristics of male Soccer players according
      to their competitive level, playing position and age group: a systematic review.
AB  - BACKGROUND: The aim of the present systematic review was to profile soccer
      players' anthropometric, physiological, and physical attributes relative to
      different competitive levels, playing positions and age groups. METHODS: The
      systematic search was conducted using different databases and according to the
      Population/Intervention or Exposure/Comparison/Outcome(s) [PICO] criteria.
      RESULTS: The present review shows that the somatotype characteristics, percentage
      (%) of body fat, maximal oxygen uptake (VO2max), repeatedsprint ability (RSA),
      running speed, strength, and muscular power of the lower limbs were the most
      powerful discriminators between male soccer players of different competitive
      levels, playing positions, and age groups. Specifically, higher VO2max, muscle
      strength, muscular power (vertical jump height), running speed (1030 m) and
      agility, and lower % of body fat were identified in elite soccer players
      (higherlevel) compared to all other competitive levels (i.e., lowerlevel:
      subelite, amateur, recreational). As for the competitive level differences,
      higher VO2max, mean anaerobic power, RSA and sprint performances (5 to 20 m), and
      lower % of body fat and lower limbs' explosive capabilities (countermovement jump
      (CMJ) and squat jump (SJ)) were found in outfielders (forwards, midfielders, and
      defenders) as compared to goalkeepers, from a very youth age (8 years old).
      Concerning age related performance, it appears that physical performance
      increased significantly with age. CONCLUSIONS: These data, together with the fact
      that each position, age category, and playing level has a different physiological
      background in male soccer players, demonstrate that training programs should be
      individualized to each position, playing level and age category, as is already
      done with goalkeepers.

PMID- 29199783
TI  - Physical and technical demands of elite beach volleyball according to playing
      position and gender.
AB  - BACKGROUND: Beach volleyball is a team sport played by two teams of two players
      on a sand court divided by a net. To date, research has mainly focused on male
      beach volleyball players. Therefore, the aim of this study was to assess work
      rest ratio and physical actions between males and females according to their
      role. METHODS: Forty-two elite beach volley players (24 males and 18 females)
      were filmed during 12 beach volleyball matches of the Swatch Major Series 2016 of
      the beach volleyball World Tour in Porec in (Croatia). Duration of point rallies,
      work rest ratio and the number of jumps and hits performed by the players
      according to their role (blockers and defenders) were recorded. RESULTS: Twenty
      one teams (12 males and 9 females) were recorded during a total of 12 matches
      comprising 11 sets for males and 9 sets for females. Males scored a total of 428
      points whereas females scored 440 points. Un-paired t-test did not show
      significant differences between males and females. Two-way analysis of variance
      showed a significant difference in the jumps performed between blockers and
      defenders and not between males and females. No significant differences in the
      other variables were detected. CONCLUSIONS: The present study provides new inside
      into female beach volleyball matches, giving preliminary normative data.
      Technical and physical aspects of beach volleyball performance appear not to be
      influenced by gender and to be only partially different according to playing
      positions. These results should be considered during the daily training
      scheduling.

PMID- 29199784
TI  - Effectiveness of individual counselling and activity monitors to promote physical
      activity among university students.
AB  - BACKGROUND: Physical activity (PA) promotion among university students is
      important to contribute to a lifelong healthy lifestyle. Nevertheless, research
      in the field is still limited in quantity, quality and generalizability. This
      study aimed at evaluating the effectiveness of two individual-based strategies
      for promoting PA among university students in such university contexts where
      course-based interventions are difficult to implement. METHOD: Thirty-three
      university students were recruited by means of face-to-face interviews and
      randomly assigned to three groups. The first group attended individual
      counselling sessions (based on the Social-Cognitive theory and the
      Transtheoretical model of behaviour change) via videoconferencing calls, the
      second used wearable PA monitors designed to motivate to PA, and the third served
      as control. Interventions lasted 12 weeks. Measures of weekly PA (self-reported
      by questionnaires and recorded by ActiGraph-GT3X+ monitors) and the stage of
      change of participants were collected at baseline (t0), immediately after the 12
      week intervention (t1), and after a 3-month follow-up (t2). RESULTS: Students in
      the individual counselling group increased self-reported energy expenditure
      between t0 and t1 and maintained this improvement at t2; on the contrary, there
      was no increase in ActiGraph measures of PA. Progression through stages of
      changes was observed in the same group at t1, followed by some relapses at t2. No
      significant differences were found neither in the group of students who used the
      PA monitors nor in the control group. CONCLUSIONS: Although measures of self
      reported PA and stage of change suggest the effectiveness of the counselling
      intervention, the results obtained with accelerometers are contrasting, probably
      due to the fact that some types of PA participants engaged in could not be
      recorder by accelerometers. Further studies are needed to determine the efficacy
      of individual counselling to promote PA in university students. The autonomous
      use of PA monitors had no effects on PA behaviour. The low participation rate in
      the study suggests to consider carefully the difficulties in motivating this
      population and in finding low time- consuming strategies to incentive
      participation.

PMID- 29199785
TI  - Acute effect of moderate-intensity concentric and eccentric exercise on cardiac
      effort, perceived exertion and interleukin-6 level in physically inactive males.
AB  - BACKGROUND: Muscle-derived interleukin-6 (IL-6) not only enhances glucose and fat
      metabolism but also has an anti-inflammatory effect that can prevent the
      development of cardiovascular disease (CVD) and metabolic syndrome. Dynamic
      resistance exercise comprises a muscle shortening and a lengthening phase known
      as concentric and eccentric contraction respectively. We compared an acute bout
      of concentric exercise (CE) with eccentric exercise (EE) for the serum IL-6
      concentration, myocardial oxygen consumption (MVO2) and rating of perceived
      exertion (RPE). METHODS: The present non-randomized crossover study involved 24
      physically inactive but apparently healthy males, aged 18-25 years with body mass
      index of 18.5-23 kg/m2. Each participant performed an acute bout of moderate
      intensity CE followed by an EE bout after two weeks of rest. Exercise bout lasted
      for about 45 minutes that involved brisk walking on a treadmill at +/-21%
      gradient for approximately 30 minutes, followed by the dumbbell exercises for
      biceps, triceps, quadriceps and hamstring muscles. MVO2 and IL-6 were estimated
      by the rate pressure product (RPP) and ELISA (enzyme-linked immunosorbent assay)
      kit respectively. Participants told their RPE after the workout. Wilcoxon or
      paired-t test were applied appropriately to compare the means. P<0.05 was
      considered significant. RESULTS: RPP, RPE, and serum IL-6 were significantly less
      after EE (164.4 +/-16.3, 12, 11.0+/-5.0 respectively) than CE (191.2+/-22.9, 13,
      12.0+/-6.3 respectively). A significant, strong and positive correlation of RPE
      was obtained with post-exercise heart-rate and RPP. CONCLUSIONS: Regular EE might
      be beneficial for individuals having a low tolerance to exertion or at risk of
      developing CVD.

PMID- 29199786
TI  - Analysis of the acceleration profile according to initial speed and positional
      role in elite professional male soccer players.
AB  - BACKGROUND: The aim of the current study was to analyse the acceleration profile
      in elite professional soccer players according to their initial speed but also
      considering players' position. METHODS: Players' accelerations profiles were
      analysed using a relative acceleration profile according to the initial speed
      (S1, from 0 to 7 km/h; S2, from 7.1 to 14.3 km/h; and S3, >=14.4 km/h) and the
      maximum acceleration. RESULTS: Within-group analyses showed that Center Backs
      (CB) performed more high intensity accelerations (likely) when they started in S1
      than S2 (ES: 0.50). Strikers (S) and Wide Midfielders (W-MD) achieved more
      accelerations (likely to almost certain) starting in S3 than S1 (ES: 0.80 and
      0.59, respectively) and S2 (ES: 0.67 and 1.09, respectively). Full Backs (FB)
      completed more accelerations (almost certain) starting in S1 and S3 than S2 (ES:
      1.39 and 1.36, respectively). Finally, Midfielders (MD) executed a greater number
      of high intensity accelerations (likely to almost certain) when they started in
      S1 than S2 (ES: 0.83) and S3 (ES: 0.66), and in S3 than S2 (ES: 4.72). Between
      group analyses showed that S, W-MD, and FB performed a greater total number of
      high intensity accelerations (very likely to almost certain) than CB (ES: 1.94,
      1.57, and 1.51, respectively) and MD (ES: 1.23, 0.92; and 0.81, respectively).
      Furthermore, MD performed substantially greater total number of high intensity
      accelerations (likely) than CB (ES: 0.56). CONCLUSIONS: Results suggest that CB
      achieved more high-intensity accelerations starting in low and moderate speed, S
      and W-MD in high speed, and FB combined low and high speed.

PMID- 29199787
TI  - Concussion prevention in youth sports: what have we overlooked?

PMID- 29199788
TI  - Adaptive thermogenesis and changes in body composition and physical fitness in
      army cadets.
AB  - BACKGROUND: To analyze the association between a 34-week military training on
      body composition, physical fitness and compensatory changes in resting energy
      expenditure (REE) recognized as adaptive thermogenesis (AT). We also explored if
      regional body composition changes were related to AT. METHODS: Twenty-nine male
      army cadets, aged 17 to 22 years were tested at baseline (T0) and after 34-weeks
      military training (T1). Physical training was performed 5 days/week during 90
      minutes/day. Measurements included body composition by dual-energy x-ray
      absorptiometry; physical fitness by 3000-m running, pull-up, 50-m freestyle
      swimming, push-up and sit-up tests; REE measured by indirect calorimetry (REEm)
      and predicted from fat-free mass (FFM), fat mass (FM) and ethnicity at T0 (REEp).
      %AT was calculated using values at T1: 100(REEm/REEp-1); and AT (kcal/day) as
      %AT/100 multiplied by baseline REEm. RESULTS: Physical training was associated
      with increases of lean soft tissue (LST) (?1.2+/-1.3 kg), FM (?1.4+/-1.3 kg), FFM
      (?1.2+/-1.3 kg) and physical fitness (P<0.01), but no REE changes (?59.6+/-168.9
      kcal/day) and AT were observed (P>0.05). Though a large variability was found, AT
      was partially explained by trunk LST (r2=0.17, P=0.027). Individuals showing a
      higher AT response demonstrated a higher trunk LST increase (?0.8+/-0.7 kg,
      P<0.05). CONCLUSIONS: The military training increased LST, FM, FFM and physical
      fitness. Though no mean changes in AT occurred, a large individual variability
      was observed with some participants increasing REE beyond the expected body
      composition changes, suggesting a spendthrift phenotype. Changes of trunk LST may
      play an important role in the AT response observed in these individuals.

PMID- 29199789
TI  - Caffeine, acute static stretching and maximum knee flexion strength.
AB  - BACKGROUND: Reductions in one repetition maximum lifts (1RM) following static
      stretching can be attributed to enhanced neural inhibition, which can be reduced
      by using stimulants like caffeine. This study compared knee-flexion 1RM following
      either static stretching (SS) or no-stretching (NS), as well as after ingesting
      either caffeine (C) or placebo (P). METHODS: Twenty-four participants (12 female,
      12 male) performed four random counterbalanced knee flexion 1RM tests. A 1RM test
      was performed for each condition at the same time of day with ~48 h separating
      each test. Static stretching consisted of 5 exercises with the 1RM being
      performed immediately following the stretching. Caffeine dose was 6 mg*kg-1 body
      weight, and the placebo was methylcellulose (520 mg). Both doses were
      administered as pills 60 min before the SS or NS procedures. RESULTS: Two-way
      repeated measures ANOVA showed a significant main effect for [NS vs. SS] (p
      <0.001, etaG2 = 0.23). The main effect for [C vs. P], and the interaction between
      [C vs. P] and [NS vs. SS] were not statistically different. Average (+/- standard
      deviation) 1RM (N) were as follows: CNS = 512 +/- 242, CSS = 474 +/- 241, PNS =
      498 +/- 247, and PSS = 460 +/- 247. CONCLUSIONS: It is concluded that static
      stretching induced strength decrements are not removed by using stimulants at
      doses allowed by sport governing organizations.

PMID- 29199790
TI  - Injury epidemiology in Italian soccer: a call for action.

PMID- 29199791
TI  - Radiation protection - still necessary?
AB  - Knowledge about the effects of small doses of radiation on health is
      accumulating, and for example the maximum level of occupational exposure allowed
      for the lens of the eye will be lowered in the next radiation law. Radiographic
      examinations are carried out at various departments in a hospital. Although the
      numbers of examinations have decreased in Finland, the examinations are more
      complex, and more radiation than before as well as longer fluoroscopy times are
      utilized in them. The guidelines for radiation are consistent despite the fact
      that there is large variation in the radiologic studies and procedures performed
      at different departments.

PMID- 29199792
TI  - Are dietary supplements necessary for a healthy person?
AB  - A dietary supplement differs from conventional foods in its appearance or way of
      using. The formulation of a dietary supplement often resembles that of medicines.
      Research evidence of the benefits of dietary supplements for healthy people is
      insufficient. A balanced, health-promoting diet will secure adequate intake of
      nutrients and, based on studies, is beneficial for the prevention of numerous
      diseases. The use of dietary supplements is justified, if giving variety to a
      diet that is inadequate in its nutritive content is not possible or successful.
      The use should be based on careful examination of the diet as well as on reliable
      biochemical assays.

PMID- 29199793
TI  - The effect of elimination diet on the growth of a child with milk allergy - a
      systematic review.
AB  - BACKGROUND: Cow's milk is the most common food allergen in children under 3 years
      of age. Milk allergy is treated by eliminating milk from the diet. METHODS: The
      present study was conducted according to international guidelines for systematic
      reviews. RESULTS: In all three articles included in the current study, children
      with milk allergy were of lower weight than the controls. Furthermore, in one of
      the studies included, growth of the children with mild allergy was stunted.
      DISCUSSION: The current review shows that milk allergy is associated with stunted
      growth in childhood. The reasons for this growth retardation are unclear.

PMID- 29199794
TI  - Emergency medicine residents in the implementation of thrombolysis for acute
      ischemic stroke.
AB  - BACKGROUND: Traditionally, neurologists have been in charge of thrombolytic
      treatment of ischemic stroke. In 2013, emergency medicine residents started
      working in the frontline at the Central Hospital of Central Finland (CHCF). They
      were trained to evaluate and give thrombolytic treatment to acute ischemic stroke
      patients out of hours, with the possibility of consulting a neurologist.
      MATHERIALS AND METHODS: Retrospective study of acute stroke patients in CHCF, who
      received thrombolytic therapy during 2012 and 2014. In 2012 thrombolytic
      treatment was initiated by neurologists only, In 2014 emergency medicine
      registrars initiated thrombolytic therapy out of hours. RESULTS: The annual
      number of tissue plasminogen activator treatment (tPA) increased and door-to
      needle time significantly decreased from 2012 to 2014. There were no significant
      differences in complications and overall functional capacity at 3 months.
      CONCLUSIONS: This study indicated that training of emergency medicine physicians
      to give thrombolytic treatment to acute ischemic stroke is feasible and may
      shorten in-hospital delays.

PMID- 29199795
TI  - The diagnostics of prostate cancer is changing.
AB  - The alternative to immediate radical treatment of prostate cancer is active
      surveillance, to which an estimated 30% of new patients with prostate cancer
      could be directed on the basis of risk classification. Active surveillance is
      based on repeated PSA measurements, digital rectal examination, repeat biopsies,
      and increasingly also on MRI. The most important prognostic factor in prostate
      cancer is still the Gleason score, forming the basis for the new grade group
      classification with the purpose of rendering active surveillance of prostate
      cancer a form of treatment that is more easily acceptable for the patients. MRI
      enables a more reliable selection of low-risk prostate cancer patients for active
      surveillance. The significance of MRI as a surveillance tool remains unclear.

PMID- 29199796
TI  - Ischemic stroke and TIA.
AB  - The key steps to improve the outcome are early diagnosis of TIA and stroke
      symptoms, access to thrombolytic and thrombectomy therapy, urgent medical
      secondary prevention and acute care in a dedicated stroke unit where assessment
      and rehabilitation are started and carried out by a multi-professional
      rehabilitation team. Long-term outcome is also improved by reinforced screening
      of specific etiologies such as atrial fibrillation and carotid stenosis.

PMID- 29199797
TI  - Working in the emergency department.
AB  - In Finland, there is a trend towards joint regional emergency departments where
      emergency medicine specialists work together with physicians from specialties.
      This collaboration will benefit the care process management and patient care.
      Moreover, an observation unit is an essential part of the modern emergency
      department.

PMID- 29199798
TI  - Specialist training of Emergency Medicine in Finland.
AB  - Emergency Medicine with a six-year specialist training became a main specialty in
      Finland in the beginning of 2013. Specialist training has developed very quickly
      over just a few years. In the frontline clinics, the clinical results have
      already reached high international quality. When developing a new specialty, not
      only active research and high-quality training but also good co-operation with
      other specialties are of utmost importance.

PMID- 29199799
TI  - Modern emergency care is aimed at a safe and quick discharge of the patient.
AB  - In Finland, there has been a need to develop emergency care in the past years
      because of the government's statutes and the need to meet the international
      standards. Emergency medicine as a newcomer specialty has encouraged the process.
      Emergency physicians are expected to take more responsibility of patient flow and
      treatment in the emergency departments (ED). The observation unit is an important
      part of the ED. It allows patients to be treated on a short-term basis, and
      patient care is efficient due to the close communication between specialties.
      Patient selection is in the essence of a well-functioning observation ward.

PMID- 29199800
TI  - Straightforward emergency care.
AB  - Emergency department is a showroom of its organization and an entry point to the
      hospital. The negative impact of sluggish processes and overcrowding in the ED is
      well acknowledged. Several tools can be used to improve patient flow in the ED.
      The specialty of emergency medicine is a crucial element which enables the
      establishment of stable, well-educated staff in the ED.

PMID- 29199801
TI  - Relevance in biology and mechanisms of immune and treatment evasion of Treponema
      pallidum: a review.
AB  - INTRODUCTION: During syphilis a compelling fight is engaged between the host's
      humoral and cellular immune responses that work to eliminate the infection and
      Treponema pallidum (T. pallidum) that manages to evade eradication and cause
      chronic infection. Different mechanisms are utilized by treponemes to overcome
      immunological response. Although penicillin (BPG) proved to be effective in
      quelling the early manifestations of the disease and consequently its
      contagiousness, questions remain about its ability to prevent the late
      complications and to provide a microbiological eradication in vivo. In fact, both
      serological and microbiological failures have been reported following
      conventional treatment. EVIDENCE ACQUISITION: We reviewed some biologic
      properties of T. pallidum in order to establish a relationship with the
      persistence of the infection and the alleged treatment resistance. EVIDENCE
      SYNTHESIS: The host humoral response, sometimes, may not protect completely
      against T. pallidum and accounts for the persistent infection and tertiary
      damages. In fact, the cell mediated response during infection may be downregulate
      in response to pathogen-derived molecules, or indirectly by generating Treg
      cells. It is also possible that there are strain types of T. pallidum with higher
      ability of evasion determining neurosyphilis. In addition, apart the impressive
      results that BPG has made on the syphilis cutaneous lesions, concerns still
      remain on its efficacy in preventing late complications. CONCLUSIONS:
      Understanding the biology of the T. pallidum may help researchers in this field
      to develop future target therapies in order to prevent persistent infection and
      progression of the disease.

PMID- 29199802
TI  - Skin eruption and cholestatic hepatic injury due to vismodegib.

PMID- 29199803
TI  - Keloid like reaction to cocaine use.

PMID- 29199804
TI  - Contact allergy: an update.
AB  - Contact allergies are common cause of eczema in all age groups and are one of the
      most common causes of occupational disability. Contact dermatitis (CD) can be
      divided into irritant and allergic contact dermatitis. Distinguishing between
      irritant and allergic triggers of CD by clinical and histologic examinations can
      be challenging. The approach to patients with CD should consist of a detailed
      (work and leisure) history, skin examination, patch tests with allergens based on
      history, physical examination, education on materials that contain the allergen
      and adequate therapy and prevention.

PMID- 29199805
TI  - " Nature step"  to prevent noncommunicable inflammatory disease.
AB  - The prevention of many diseases has significantly improved by intervening in
      known risk factors. However, the causes of the increase in allergy and type 1
      diabetes are unknown. These diseases are often associated with a low-grade
      inflammation and immunological imbalance. The lifestyle and environment of
      urbanized populations have changed causing imbalance in the human normal flora
      and affecting immune regulation. We discuss everyday factors affecting immune
      regulation, using allergy as an example. Health may be promoted through the
      "nature step", by supporting the connection between humans and nature.

PMID- 29199806
TI  - Selective progesterone receptor modulators: new possibilities for gynecologic
      hormone therapy.
AB  - Progesterone regulates several female reproductive functions. Progesterone and
      synthetic progestins derived from it have long been utilized in gynecology. The
      effects of these steroids in target cells are mediated via progesterone
      receptors, Progesterone  receptors are also the target of action of selective
      progesterone receptor modulators. Of the molecules of this newer group of drugs,
      two are presently in clinical use. Mifepristone is used in nonsurgical abortion,
      in softening of the cervix before surgical abortion, and in the induction of
      labor in cases of intrauterine death. The indications of ulipristal acetate are
      postcoital contraception and treatment of uterine myomas and the resulting
      symptoms.

PMID- 29199807
TI  - Health risks of drugs in Finland - can the risks be managed?
AB  - In the HUUTI consortium research project, the illicit use of drugs and
      consequences thereof among Finnish people were studied, also seeking possible new
      pharmacological therapies for dependency problems. The epidemiological part
      included 4,817 persons, who attended the services for drug users at Helsinki
      Deaconess Institute between 1997 and 2008. The majority were below 35 years of
      age. The average level of education was low and the proportion of employed was
      small. On the average, 3.5 different substances were being used, of which
      buprenorphine and amphetamine were the most common primary drugs, cannabis being
      the most common secondary drug. An almost tenfold mortality was observed in the
      follow-up comparison with the reverence population.

PMID- 29199808
TI  - How to identify DRESS, drug reaction with eosinophilia and systemic symptoms?
AB  - DRESS (drug reaction with eosinophilia and systemic symptoms) is a rare, severe
      multiorgan  adverse drug reaction. Antiepileptic age's and antibiotics are the
      most frequently reported causative agents. Compared with other drug reactions,
      DRESS demonstrates a long latency period thus complicating recognition and
      diagnosis. DRESS is defined as presence of fever, skin eruption, hematologic
      abnormalities and systemic involvement, especially liver injury. Withdrawal of
      the culprit drug, commencement of systemic corticosteroid and supportive care are
      the mainstay of treatment. The majority of patients recover completely after drug
      withdrawal and appropriate therapy. Some patients suffer from chronic sequelae or
      even death.

PMID- 29199809
TI  - ?

PMID- 29199810
TI  - Ketamine as treatment for depression.
AB  - Ketamine infusions  administered intravenously 1 to 3 times per week are the
      quickest and most effective treatment for depression. Short-course ketamine
      medication is established treatment both for unipolar depression and depressive
      episodes of bipolar affective disorder. Ketamine is suitable for initiating the
      treatment for treatment-resistant depression, alleviation of suicidal tendencies,
      and treatment of depressive patients suffering from simultaneous pain. The safety
      of prolonged treatment with ketamine is not known to sufficient degree. However,
      even long periods (up to 1.5 years) of ketamine treatment have not been
      associated with adverse effects. It would be appropriate to use short-course
      ketamine treatment more often than is currently done.

PMID- 29199811
TI  - Hard Carbon Wrapped Na3V2(PO4)3@C Porous Composite Extending Cycling Lifespan for
      Sodium-Ion Batteries.
AB  - Although the NASICON-type of Na3V2(PO4)3 is regarded as a potential cathode
      candidate for advanced sodium-ion batteries (SIBs), it has an undesirable rate
      performance and low cyclability, which are a result of its poor electronic
      conductivity. Here, we utilized conductive polyaniline (PANI) grown in situ to
      obtain the hard carbon-coated porous Na3V2(PO4)3@C composite (NVP@C@HC) with a
      typically simple and effective sol-gel process. Based on the restriction of
      double carbon layers, the NVP size decreases distinctly, which can curtail the
      sodium-ion diffusion distance and enhance the electronic conductivity. As
      expected, the product displays good discharge capacity (111.6 mA h g-1 at 1 C),
      outstanding rate capacity (60.4 mA h g-1 at 50 C), and remarkable cycling
      stability (63.3 mA h g-1 with a retention of 83.3% at 40 C over 3000 cycles).
      Also, it performs a long-term cycling capacity of 58.5 mA h g-1 exceeding 15 000
      cycles at 20 C (with a capacity loss of 0.24% per cycle).

PMID- 29199812
TI  - Strain-Induced Tailoring of Oxygen-Ion Transport in Highly Doped CeO2
      Electrolyte: Effects of Biaxial Extrinsic and Local Lattice Strain.
AB  - We explored oxygen-ion transport in highly doped CeO2 through density-functional
      theory calculations. By applying biaxial strain to 18.75 mol % CeO2:Gd, we
      predicted the average migration-barrier energy with six different pathways, with
      results in good agreement with those of experiments. Additionally, we found that
      the migration-barrier energy could be lowered by increasing the tetrahedron
      volume, including the space occupied by the oxygen vacancy. Our results indicate
      that the tetrahedron volume can be expanded by larger codopants, as well as
      biaxial tensile strain. Thus, the combination of thin-film structure and codoping
      could offer a new approach to accelerate oxygen-ion transport.

PMID- 29199813
TI  - Nanostructured Composites of Bi1-xSbx Nanoparticles and Carbon Nanotubes and the
      Characterization of Their Thermoelectric Properties.
AB  - The impact of inclusions of carbon nanotubes (CNT) on the thermoelectric
      properties of nanostructured Bi1-xSbx alloys with an Sb content between 10 and
      20% was investigated for varying amounts of CNT. Three series of Bi1-xSbx pellets
      with 0, 0.3, and 0.5 wt % CNT were synthesized by mechanical alloying followed by
      uniaxial pressing. The resistivity was investigated in the temperature range from
      30 to 500 K, revealing an enlargement of the band gap due to nanostructuring of
      the Bi1-xSbx alloy, which is even more pronounced for alloys including CNT. This
      enlargement is attributed to a modification of the interface between the Bi1-xSbx
      nanoparticles by a graphene-like coating, which is formed during the fabrication
      process due to the addition of CNT. Measurements of the Seebeck coefficient and
      the thermal conductivity were also performed to determine the thermoelectric
      properties. In total, the CNT-containing samples show a significant improvement
      of the figure of merit up to 250% for the Bi0.88Sb0.12 composition with 0.3 wt %
      CNT due to the interface modification between the nanoparticles, demonstrating
      the beneficial effect of CNT on the thermoelectric properties.

PMID- 29199814
TI  - Photochemically Activated Motors: From Electrokinetic to Diffusion Motion
      Control.
AB  - Self-propelled micro/nanomotors that can transform chemical energy from the
      surrounding environment into mechanical motion are cutting edge nanotechnologies
      with potential applications in biomedicine and environmental remediation. These
      applications require full understanding of the propulsion mechanisms to improve
      the performance and controllability of the motors. In this work, we demonstrate
      that there are two competing chemomechanical mechanisms at semiconductor/metal
      (Si/Pt) micromotors in a pump configuration under visible light exposure. The
      first propulsion mechanism is driven by an electro-osmotic process stemmed from a
      photoactivation reaction mediated by H2O2, which takes place in two separated
      redox reactions at the Si and Pt interfaces. One reaction involves the oxidation
      of H2O2 at the silicon side, and the other the H2O2 reduction at the metal side.
      The second mechanism is not light responsive and is triggered by the redox
      decomposition of H2O2 exclusively at the Pt surface. We show that it is possible
      to enhance/suppress one mechanism over the other by tuning the surface roughness
      of the micromotor metal. More specifically, the actuation mechanism can be
      switched from light-controlled electrokinetics to light-insensitive diffusio
      osmosis by only increasing the metal surface roughness. The different actuation
      mechanisms yield strikingly different fluid flow velocities, electric fields, and
      light sensitivities. Consequently, these findings are very relevant and can have
      a remarkable impact on the design and optimization of photoactivated catalytic
      devices and, in general, on bimetallic or insulating-metallic motors.

PMID- 29199815
TI  - Graphene/PbS-Quantum Dots/Graphene Sandwich Structures Enabled by Laser Shock
      Imprinting for High Performance Photodetectors.
AB  - Quantum dots (QDs) integrated 2-dimensional (2D) materials have great potential
      for photodetector applications due to the excellent light absorption of QDs and
      ultrafast carrier transportation of 2D materials. However, there is a main issue
      that prevents efficient carrier transportation and ideal performance of
      photodetectors: the high interfacial resistance between 2D materials and QDs due
      to the bad contacts between 2D/0D interface, which makes sluggish carrier
      transfer from QDs to 2D materials. Here, a sandwich structure (graphene/PbS
      QDs/graphene) with seamless 2D/0D contact was fabricated by laser shock
      imprinting, which opto-mechanically tunes the morphology of 2D materials to
      perfectly wrap on 0D materials and efficiently collect carriers from the PbS-QDs.
      It is found that this seamless integrated 2D/0D/2D structure significantly
      enhanced the carrier transmission, photoresponse gain (by 2*), response time (by
      20*), and photoresponse speed (by 13*). The response time (~30 ms) and Ip/ Id
      ratio (13.2) are both over 10* better than the reported hybrid graphene
      photodetectors. This is due to the tight contact and efficient gate-modulated
      carrier injection from PbS-QDs to graphene. The gate voltage dictates whether
      electrons or holes dominate the carrier injection from PbS-QDs to graphene.

PMID- 29199816
TI  - Toward Solid-State 3D-Microbatteries Using Functionalized Polycarbonate-Based
      Polymer Electrolytes.
AB  - 3D microbatteries (3D-MBs) impose new demands for the selection, fabrication, and
      compatibility of the different battery components. Herein, solid polymer
      electrolytes (SPEs) based on poly(trimethylene carbonate) (PTMC) have been
      implemented in 3D-MB systems. 3D electrodes of two different architectures,
      LiFePO4-coated carbon foams and Cu2O-coated Cu nanopillars, have been coated with
      SPEs and used in Li cells. Functionalized PTMC with hydroxyl end groups was found
      to enable uniform and well-covering coatings on LiFePO4-coated carbon foams,
      which was difficult to achieve for nonfunctionalized polymers, but the cell
      cycling performance was limited. By employing a SPE prepared from a copolymer of
      TMC and caprolactone (CL), with higher ionic conductivity, Li cells composed of
      Cu2O-coated Cu nanopillars were constructed and tested both at ambient
      temperature and 60  degrees C. The footprint areal capacity of the cells was ca.
      0.02 mAh cm-2 for an area gain factor (AF) of 2.5, and 0.2 mAh cm-2 for a
      relatively dense nanopillar-array (AF = 25) at a current density of 0.008 mA cm-2
      under ambient temperature (22 +/- 1  degrees C). These results provide new routes
      toward the realization of all-solid-state 3D-MBs.

PMID- 29199817
TI  - Microporous Co@C Nanoparticles Prepared by Dealloying CoAl@C Precursors:
      Achieving Strong Wideband Microwave Absorption via Controlling Carbon Shell
      Thickness.
AB  - Excellent magnetic features make Co-based materials promising candidates as high
      performance microwave absorbers. However, it is still a significant challenge for
      Co-based absorbers to possess high-intensity and broadband absorption
      simultaneously, owing to the lack of dielectric loss and impedance matching.
      Herein, microporous Co@C nanoparticles (NPs) with carbon shell thicknesses
      ranging from 1.8-4.9 nm have been successfully synthesized by dealloying CoAl@C
      precursors. All of the samples exhibit high microwave absorption performance. The
      microporous Co@C sample possessing a carbon shell of 1.8 nm exhibits the highest
      absorption intensity among these samples with a minimum reflection loss (RL) of 
      141.1 dB, whose absorption bandwidth for RL <= -10 dB is 7.3 GHz. As the
      thickness of the carbon shell increases, the absorption bandwidth of the NPs
      becomes wider. For the sample with the carbon shell thickness of 4.9 nm, the
      absorption bandwidth for RL <= -10 dB reaches a record high of 13.2 GHz. The
      outstanding microwave attenuation properties are attributed to the dielectric
      loss of the carbon shell, the magnetic loss of the Co core, and the cooperation
      of the core-shell structure and microporous morphology. The strong wideband
      microwave absorption of the carbon-coated microporous Co NPs highlights their
      potential applications in microwave absorbing systems.

PMID- 29199818
TI  - Precision Medicine in Pediatric Neurooncology: A Review.
AB  - Central nervous system tumors are the leading cause of cancer related death in
      children. Despite much progress in the field of pediatric neurooncology, modern
      combination treatment regimens often result in significant late effects, such as
      neurocognitive deficits, endocrine dysfunction, secondary malignancies, and a
      host of other chronic health problems. Precision medicine strategies applied to
      pediatric neurooncology target specific characteristics of individual patients'
      tumors to achieve maximal killing of neoplastic cells while minimizing unwanted
      adverse effects. Here, we review emerging trends and the current literature that
      have guided the development of new molecularly based classification schemas,
      promising diagnostic techniques, targeted therapies, and delivery platforms for
      the treatment of pediatric central nervous system tumors.

PMID- 29199819
TI  - Conjugated Polymer Containing Organic Radical for Optical/MR Dual-Modality
      Bioimaging.
AB  - Optical/MRI bimodal probes have attracted much attention due to palmary soft
      tissue resolution and high imaging sensitivity. In this study, poly[fluorene-co
      alt-p-phenylene] containing organic radical (PFP-TEMPO+) is successfully
      developed for optical and MRI dual-modality bioimaging. PFP-TEMPO+ displays
      advanced properties such as fluorescence emission, high photostablilty,
      reasonable T1 relaxation effect, low cytotoxicity, and good biocompatibility.
      Moreover, the ability of PFP-TEMPO+ for tumor tissues imaging confirms that it
      could be used as an optical and MRI imaging probe for in vivo imaging. The
      results of the present work disclose the potential applications of PFP-TEMPO+ as
      an optical and MRI contrast agent.

PMID- 29199820
TI  - Multimodal Probes: Superresolution and Transmission Electron Microscopy Imaging
      of Mitochondria, and Oxygen Mapping of Cells, Using Small-Molecule Ir(III)
      Luminescent Complexes.
AB  - We describe an Ir(III)-based small-molecule, multimodal probe for use in both
      light and electron microscopy. The direct correlation of data between light- and
      electron-microscopy-based imaging to investigate cellular processes at the
      ultrastructure level is a current challenge, requiring both dyes that must be
      brightly emissive for luminescence imaging and scatter electrons to give contrast
      for electron microscopy, at a single working concentration suitable for both
      methods. Here we describe the use of Ir(III) complexes as probes that provide
      excellent image contrast and quality for both luminescence and electron
      microscopy imaging, at the same working concentration. Significant contrast
      enhancement of cellular mitochondria was observed in transmission electron
      microscopy imaging, with and without the use of typical contrast agents. The
      specificity for cellular mitochondria was also confirmed with MitoTracker using
      confocal and 3D-structured illumination microscopy. These phosphorescent dyes are
      part of a very exclusive group of transition-metal complexes that enable imaging
      beyond the diffraction limit. Triplet excited-state phosphorescence was also
      utilized to probe the O2 concentration at the mitochondria in vitro, using
      lifetime mapping techniques.

PMID- 29199821
TI  - WO3 Nanoarray: An Efficient Electrochemical Oxygen Evolution Catalyst Electrode
      Operating in Alkaline Solution.
AB  - It is fascinating to design and synthesize high-efficiency and noble-metal-free
      alkaline oxygen evolution reaction (OER) electrocatalysts. In this Communication,
      we describe the one-step hydrothermal synthesis of a WO3 nanoarray directly grown
      on conductive carbon cloth (WO3/CC) for efficient water oxidation in 1.0 M KOH.
      As a monolithically integrated array catalyst, WO3/CC exhibits superior OER
      activity demanding overpotential as low as 280 mV to afford a benchmarking
      catalytic current density of 10 mA cm-2. It is worth noting that WO3/CC also
      possesses strong electrochemical durability with 95% Faradaic yields.

PMID- 29199822
TI  - Hyperthermophilic Composting Accelerates the Removal of Antibiotic Resistance
      Genes and Mobile Genetic Elements in Sewage Sludge.
AB  - Composting is an efficient way to convert organic waste into fertilizers.
      However, waste materials often contain large amounts of antibiotic resistance
      genes (ARGs) and mobile genetic elements (MGEs) that can reduce the efficacy of
      antibiotic treatments when transmitted to humans. Because conventional composting
      often fails to remove these compounds, we evaluated if hyperthermophilic
      composting with elevated temperature is more efficient at removing ARGs and MGEs
      and explored the underlying mechanisms of ARG removal of the two composting
      methods. We found that hyperthermophilic composting removed ARGs and MGEs more
      efficiently than conventional composting (89% and 49%, respectively).
      Furthermore, the half-lives of ARGs and MGEs were lower in hyperthermophilic
      compositing compared to conventional composting (67% and 58%, respectively). More
      efficient removal of ARGs and MGEs was associated with a higher reduction in
      bacterial abundance and diversity of potential ARG hosts. Partial least-squares
      path modeling suggested that reduction of MGEs played a key role in ARG removal
      in hyperthermophilic composting, while ARG reduction was mainly driven by changes
      in bacterial community composition under conventional composting. Together these
      results suggest that hyperthermophilic composting can significantly enhance the
      removal of ARGs and MGEs and that the mechanisms of ARG and MGE removal can
      depend on composting temperature.

PMID- 29199823
TI  - Two Unique Crystalline Semiconductor Zeolite Analogues Based on Indium Selenide
      Clusters.
AB  - Developing the structural diversity of microporous zeolitic frameworks with
      integrated semiconducting properties is promising but remains a challenge.
      Reported here are two unique crystalline semiconductor zeolite analogues
      constructed from two kinds of indium selenide clusters with augmented ctn and
      zeolite-type sod networks. The intrinsic semiconducting nature in these In-Se
      domains gives rise to pore-size-dependent and visible-light-driven photocatalytic
      activity for organic dye degradation.

PMID- 29199824
TI  - One-Pot Conversion of Methane to Light Olefins or Higher Hydrocarbons through H
      SAPO-34-Catalyzed in Situ Halogenation.
AB  - Methane was converted to light olefins (ethene and propene) or higher
      hydrocarbons in a continuous flow reactor below 375  degrees C over H-SAPO-34
      catalyst via an in situ halogenation (chlorination/bromination) protocol. The
      reaction conditions can be efficiently tuned toward selective monohalogenation of
      methane to methyl halides or their in situ oligomerization to higher
      hydrocarbons. The presence of C5+ hydrocarbons in the reaction products clearly
      indicates that by using a properly engineered catalyst under optimized reaction
      conditions, hydrocarbons in the gasoline range can be produced. This approach has
      significant potential for feasible application in natural gas refining to
      gasoline and materials under moderate operational conditions.

PMID- 29199825
TI  - Unusual Aggregation Arrangement of Eu-Containing Polyoxometalate Hybrid in a
      Protic Ionic Liquid with Improved Luminescence Property.
AB  - Hybridization of polyoxometalates (POMs) with cationic surfactants offers the
      opportunity to greatly improve their functionalities as well as processabilities.
      Here, a surfactant-encapsulated Eu-containing POM complex (SEP) was formed via
      electrostatic interaction between 1-octadecyl-3-methylimidazolium bromide (OB)
      and Na9(EuW10O36).32H2O (EuW10). SEP was first self-assembled in a protic ionic
      liquid to prepare the soft aggregates to fundamentally avoid the fluorescence
      quenching by water molecules. The structures and photophysical properties of SEP
      or aggregates were investigated thoroughly by NMR and FTIR spectroscopy, optical
      and electron microscopy, small-angle X-ray scattering, and fluorescence
      measurements. The formed gel-like aggregates were found to compose of three
      dimensional networks of microribbons with an interdigitated layered molecular
      packing of SEP, which was different from the usual inverse bilayer model of POM
      hybrids in common organic solvents. Compared to EuW10 solid or its aqueous
      solution, both SEP and its aggregates exhibited intense red luminescence with
      much improved lifetime and quantum efficiency. In addition, the soft aggregates
      exhibited an efficient energy transfer and an obviously enhanced
      monochromaticity, owning to the organized arrangement of EuW10 units and a
      confined microenvironment to isolate them from each other between adjacent
      layers. The obtained results will not only present a useful reference to the
      aggregation behavior of POM hybrids in ionic liquids, but also provide an easy
      way to design EuW10 luminescent soft materials based on the nonaqueous media.

PMID- 29199826
TI  - Luminescent 3D Lanthanide-Cadmium Heterometal-Organic Frameworks with Chemical
      Stability and Selective Luminescent Sensing.
AB  - Four novel three-dimensional (3D) 4d-4f heterometal-organic compounds,
      [LnCd2(Pbc)4(Meimdc)(H2O)].3H2O (Ln = Eu, 1a; Tb, 1b; Sm, 1c; Dy, 1d) (HPbc = 4
      (4-pyridinyl)benzoic acid; H3Meimdc = 2-methyl-1H-4,5-imidazole-dicarboxylic
      acid), have been successfully prepared by a hydrothermal method. All the
      compounds are isostructural and show three-dimensional microporous pillar-layered
      structures with uncoordinated carboxylate sites hung in the channels. Compound 1a
      possesses excellent chemical stability. The luminescent investigations show that
      compounds 1a, 1b, 1c, and 1d display the characteristic emission bands of Ln3+
      ions. Compound 1a exhibits a good potential as a luminescent sensor material for
      multi-responsive Ag+, Cu2+, Zn+, Co2+, and Ni2+ cations and some organic amines.
      Interestingly, 1a can capture Ag+, Cu2+, Zn+, Co2+, and Ni2+ cations and shows
      cation-dependent colorimetric response, which indicates the potential for naked
      sensing.

PMID- 29199827
TI  - Reaction Mechanisms and Structural and Physicochemical Properties of Caffeic Acid
      Grafted Chitosan Synthesized in Ascorbic Acid and Hydroxyl Peroxide Redox System.
AB  - The ascorbic acid (AA) and hydroxyl peroxide (H2O2) redox pair induced free
      radical grafting reaction is a promising approach to conjugate phenolic groups
      with chitosan (CS). In order to reveal the exact mechanisms of the AA/H2O2 redox
      pair induced grafting reaction, free radicals generated in the AA/H2O2 redox
      system were compared with hydroxyl radical (*OH) produced in the Fe2+/H2O2 redox
      system. Moreover, the structural and physicochemical properties of caffeic acid
      grafted CS (CA-g-CS) synthesized in these two redox systems were compared.
      Results showed that only ascorbate radical (Asc*-) was produced in the AA/H2O2
      system. The reaction between Asc*- and CS produced novel carbon-centered
      radicals, whereas no new free radicals were detected when *OH reacted with CS.
      Thin layer chromatography, UV-vis, Fourier transform infrared, and nuclear
      magnetic resonance spectroscopic analyses all confirmed that CA was successfully
      grafted onto CS through Asc*-. However, CA could be hardly grafted onto CS via
      *OH. CA-g-CS synthesized through Asc*- exhibited lower thermal stability and
      crystallinity than the reaction product obtained through *OH. For the first time,
      our results demonstrated that the synthesis of CA-g-CS in the AA/H2O2 redox
      system was mediated by Asc*- rather than *OH.

PMID- 29199828
TI  - Efficient Coproduction of Mannanase and Cellulase by the Transformation of a
      Codon-Optimized Endomannanase Gene from Aspergillus niger into Trichoderma
      reesei.
AB  - Cellulase and mannanase are both important enzyme additives in animal feeds.
      Expressing the two enzymes simultaneously within one microbial host could
      potentially lead to cost reductions in the feeding of animals. For this purpose,
      we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of
      Trichoderma reesei. By comparing the free energies and the local structures of
      the nucleotide sequences, one optimized sequence was finally selected and
      transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon
      optimized gene was expressed to a higher level than the original one. Further
      expressing the codon-optimized gene in a mutated T. reesei strain through fed
      batch cultivation resulted in coproduction of cellulase and mannanase up to 1376
      U.mL-1 and 1204 U.mL-1, respectively.

PMID- 29199831
TI  - Controlling the C(sp3)-C(sp2) Axial Conformation in the Enantioselective Friedel
      Crafts-Type Alkylation of beta-Naphthols with Inden-1-ones.
AB  - The Friedel-Crafts-type reaction between properly functionalized inden-1-ones and
      2-naphthols generates a hindered single bond which displays a unique preference
      for an antiperiplanar conformational diastereoisomer. The steric hindrance and
      the presence of an enantioenriched stereogenic center control the distribution of
      the two diastereomeric conformers at equilibrium and increase the energy for the
      rotation of the C(sp3)-C(sp2) single bond.

PMID- 29199830
TI  - Receptor-Mediated Endocytosis of Nanoparticles: Roles of Shapes, Orientations,
      and Rotations of Nanoparticles.
AB  - A complete understanding of the interactions between nanoparticles (NPs) and the
      cell membrane is essential for the potential biomedical applications of NPs. The
      rotation of the NP during the cellular wrapping process is of great biological
      significance and has been widely observed in experiments and simulations.
      However, the underlying mechanisms of the rotation and their potential influences
      on the wrapping behavior are far from being fully understood. Here, by coupling
      the rotation of the NP with the diffusion of the receptors, we set up a model to
      theoretically investigate the wrapping pathway and the internalization rate of
      the rotatable NP in the receptor-mediated endocytosis. Based on this model, it is
      found that the endocytosis proceeds through the symmetric-asymmetric or
      asymmetric-symmetric-asymmetric wrapping pathway due to the bending and membrane
      tension competition induced rotation of NP. In addition, we show that the
      wrapping rate in the direction that the wrapping proceeds can be largely
      accelerated by the rotation. Moreover, the time to fully wrap the NP depends not
      only on the size and shape of the NP but also on its rotation and initial
      orientation. These results reveal the roles of the shape, rotation, and initial
      orientation of the NP on the receptor-mediated endocytosis and may provide
      guidelines for the design of NP-based drug delivery systems.

PMID- 29199829
TI  - Simple Quantum Dynamics with Thermalization.
AB  - In this paper, we introduce two simple quantum dynamics methods. One is based on
      the popular surface-hopping method, and the other is based on rescaling of the
      propagation on the bath ground-state potential surface. The first method is
      special, as it avoids specific feedback from the simulated quantum system to the
      bath and can be applied for precalculated classical trajectories. It is based on
      the equipartition theorem to determine if hops between different potential energy
      surfaces are allowed. By comparing with the formally exact Hierarchical Equations
      Of Motion approach for four model systems we find that the method generally
      approximates the quantum dynamics toward thermal equilibrium very well. The
      second method is based on rescaling of the nonadiabatic coupling and also neglect
      the effect of the state of the quantum system on the bath. By the nature of the
      approximations, they cannot reproduce the effect of bath relaxation following
      excitation. However, the methods are both computationally more tractable than the
      conventional fewest switches surface hopping, and we foresee that the methods
      will be powerful for simulations of quantum dynamics in systems with complex bath
      dynamics, where the system-bath coupling is not too strong compared to the
      thermal energy.

PMID- 29199832
TI  - Domain Formation and Conformational Changes in Gold Nanoparticle Conjugates
      Studied Using DPD Simulations.
AB  - A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA)
      and thiolated polyethylene glycol (SH-PEG) is simulated using dissipative
      particle dynamics (DPD) methods, obtaining an excellent agreement with previous
      experimental observations. The simulations cover the isolated components (AuNP,
      MUA, and SH-PEG), as well as pairs of components, and finally the all three
      components at the same time. In this latter case, changes in the order of
      addition of MUA and SH-PEG over the AuNP are also considered. The AuNP is formed
      by independent gold beads and keeps an almost spherical shape throughout the
      simulation. MUA forms micelles of four to six MUA units when dispersed in water,
      while SH-PEG stays individually and well solvated. When exposed to AuNP, both
      molecules show a tendency to form patches on the surface. SH-PEG displays two
      different conformations (radial and tangential) depending on its relative
      concentration and the presence of other molecules at the NP surface. When
      combined at subsaturation concentrations, MUA arrives faster to the AuNP surface
      than SH-PEG and forms patches while SH-PEG occupies the remaining free surface.
      In these conditions, the order of addition of the different components partially
      alters these results. When SH-PEG is added over an already formed MUA/AuNP
      partial layer, it adopts a radial conformation over the MUA formed patches; on
      the contrary, if MUA is added over an already formed SH-PEG/AuNP partial layer,
      much less SH-PEGs adopt a radial conformation and MUA patches are significantly
      smaller.

PMID- 29199833
TI  - Single-Cell Optical Distortion Correction and Label-Free 3D Cell Shape
      Reconstruction on Lattices of Nanostructures.
AB  - Imaging techniques can be compromised by aberrations. Especially when imaging
      through biological specimens, sample-induced distortions can limit localization
      accuracy. In particular, this phenomenon affects localization microscopy,
      traction force measurements, and single-particle tracking, which offer high
      resolution insights into biological tissue. Here we present a method for
      quantifying and correcting the optical distortions induced by single, adherent,
      living cells. The technique uses periodically patterned gold nanostructures as a
      reference framework to quantify optically induced displacements with micrometer
      scale sampling density and an accuracy of a few nanometers. The 3D cell shape and
      a simplified geometrical optics approach are then utilized to remap the
      microscope image. Our experiments reveal displacements of up to several hundred
      nanometers, and in corrected images these distortions are reduced by a factor of
      3. Conversely, the relationship between cell shape and distortion provides a
      novel method of 3D cell shape reconstruction from a single image, enabling label
      free 3D cell analysis.

PMID- 29199834
TI  - Understanding Solvent Spreading for Langmuir Deposition of Nanomaterial Films: A
      Hansen Solubility Parameter Approach.
AB  - To prepare high-quality Langmuir films of 2D materials it is important to select
      a solvent optimized for both exfoliation and spreading at the air-water
      interface. Whereas it is generally accepted that exfoliation and stabilization of
      2D materials is well-described using the Hansen solubility parameter theory, a
      complementary description of solvent spreading behavior is lacking. To this end
      we develop an understanding of solvent spreading using a Hansen solubility
      parameter framework. Our model accurately predicts the behavior of both water
      immiscible and water-miscible solvents in Langmuir film formation experiments. We
      demonstrate that spreading behavior can be modified by controlling the surface
      pressure of the subphase using an amphiphilic species and accordingly utilize
      this approach to determine the maximum spreading pressure for a selection of
      solvents. Ultimately, by building on this understanding we open up additional
      routes to optimize the preparation of Langmuir films of 2D materials and other
      nanoparticles.

PMID- 29199835
TI  - Directed Aromatic C-H Activation/Acetoxylation Catalyzed by Pd Nanoparticles
      Supported on Graphene Oxide.
AB  - The first solid-supported directed aromatic C-H activation/acetoxylation has been
      successfully developed by using palladium nanoparticles supported on graphene
      oxide (PdNPs/GO) as a catalyst. The practicability of this method is demonstrated
      by simple preparation of catalyst, high catalytic efficiency, wide functional
      group tolerance, and easy scale up of the reaction. A hot filtration test and
      Hg(0) poisoning test indicate the heterogeneous nature of the catalytic active
      species.

PMID- 29199836
TI  - Molecular Dynamics at the Interface between Ice and Poly(vinyl alcohol) and Ice
      Recrystallization Inhibition.
AB  - Ice formation is a ubiquitous process that poses serious challenges for many
      areas. Nature has evolved a variety of different mechanisms to regulate ice
      formation. For example, many cold-adapted species produce antifreeze proteins
      (AFPs) and/or antifreeze glycoproteins (AFGPs) to inhibit ice recrystallization.
      Although several synthetic substitutes for AF(G)Ps have been developed, the
      fundamental principles of designing AF(G)P mimics are still missing. In this
      study, we explored the molecular dynamics of ice recrystallization inhibition
      (IRI) by poly(vinyl alcohol) (PVA), a well-recognized ice recrystallization
      inhibitor, to shed light on the otherwise hidden ice-binding mechanisms of chain
      polymers. Our molecular dynamics simulations revealed a stereoscopic, geometrical
      match between the hydroxyl groups of PVA and the water molecules of ice, and
      provided microscopic evidence of the adsorption of PVA to both the basal and
      prism faces of ice and the incorporation of short-chain PVA into the ice lattice.
      The length of PVA, i.e., the number of hydroxyl groups, seems to be a key factor
      dictating the performance of IRI, as the PVA molecule must be large enough to
      prevent the joining together of adjacent curvatures in the ice front. The
      findings in this study will help pave the path for addressing a pressing
      challenge in designing synthetic ice recrystallization inhibitors rationally, by
      enriching our mechanistic understanding of IRI process by macromolecules.

PMID- 29199837
TI  - Psychometric evaluation of the Mini International Neuropsychiatric Interview for
      Children and Adolescents (MINI-KID).
AB  - The goals of the study were to examine test-retest reliability, informant
      agreement and convergent and discriminant validity of nine DSM-IV-TR psychiatric
      disorders classified by parent and youth versions of the Mini International
      Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Using samples
      drawn from the general population and child mental health outpatient clinics, 283
      youth aged 9 to 18 years and their parents separately completed the MINI-KID with
      trained lay interviewers on two occasions 7 to 14 days apart. Test-retest
      reliability estimates based on kappa (kappa) went from 0.33 to 0.79 across
      disorders, samples and informants. Parent-youth agreement on disorders was low
      (average kappa = 0.20). Confirmatory factor analysis provided evidence supporting
      convergent and discriminant validity. The MINI-KID disorder classifications
      yielded estimates of test-retest reliability and validity comparable to other
      standardized diagnostic interviews in both general population and clinic samples.
      These findings, in addition to the brevity and low administration cost, make the
      MINI-KID a good candidate for use in epidemiological research and clinical
      practice. (PsycINFO Database Record

PMID- 29199838
TI  - Evaluating the eight-item Patient Health Questionnaire's psychometric properties
      with Mexican and Central American descent university students.
AB  - Depression can be a serious aliment influencing the lives of millions of persons.
      Person's health conditions worsen and daily functioning declines in the presence
      of depression. However, little attention has been given to how depression is
      accurately assessed in diverse populations from other countries residing in the
      United States. Thus, this study examined the factor structure, factorial
      invariance, concurrent validity, and convergent validity of the widely used 8
      item Patient Health Questionnaire (PHQ-8) among emerging adults of Mexican and
      Central American (e.g., Salvadorians, Guatemalans) men and women residing in the
      United States. Undergraduate student participants (n = 2,782) completed an online
      or paper-and-pencil version of the assessment. Support was found for two-factor
      and one-factor solutions; however, the unidimensional structure was recommended
      due to the very high correlation between the two factors (r >= .87). The
      unidimensional scale was invariant between (a) Mexican and Central American
      descent and (b) men and women. Depressive symptoms (as measured in the PHQ-8)
      were significantly correlated with another valid and reliable measured of
      depression, and scores on the PHQ-8 were significantly correlated with
      theoretically related variables (i.e., quality of life, parental support, and
      perceived stress). (PsycINFO Database Record

PMID- 29199839
TI  - A systematic review of the efficacy of creative arts therapies in the treatment
      of adults with PTSD.
AB  - OBJECTIVE: There is a growing body of literature supporting the use of creative
      arts therapies; however, the efficacy of creative arts therapies in the treatment
      of posttraumatic stress disorder (PTSD) has not been systematically evaluated.
      The aim of this systematic review was to examine the efficacy of creative arts
      therapy including music therapy, art therapy, dance/movement therapy, and drama
      therapy, in the treatment of PTSD. METHOD: Ten databases were searched for peer
      reviewed literature published from inception to December 2016. Studies were
      included in the review if they used a randomized controlled trial (RCT), a pseudo
      RCT, or a controlled study design; tested the efficacy of one of the creative
      arts therapies described above; and reported changes to PTSD diagnosis or
      symptomatology. RESULTS: From an initial yield of 1,918 records, 1,653 records
      were screened on title and abstract and 125 were screened at full-text. Seven
      studies met the inclusion criteria for review, with four studies investigating
      art therapy, two studies investigating music therapy, and a final study
      investigating drama therapy. Individual studies were initially rated on a
      standardized quality and bias checklist, and then GRADE was used to rate the
      overall evidence for each intervention. The evidence for music therapy, art
      therapy, and drama therapy was ranked as low to very low, with no studies found
      for dance/movement therapy. Generally, the quality of the trials was very poor.
      Future directions for this field of research are to improve the scientific
      quality of the research trials in this area. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 29199840
TI  - An examination of sex differences on neurocognitive functioning and behavior
      problems in maltreated youth.
AB  - OBJECTIVE: In the developmental traumatology model, the biological construct of
      sex is considered a moderator that may negatively influence child maltreatment
      sequelae including those pertaining to neurocognitive function. METHOD: This
      study examined sex-differences in neurocognitive function and behavior problems
      in maltreated boys (n = 42), maltreated girls (n = 56) versus nonmaltreated boys
      (n = 45) and girls (n = 59). Maltreated boys were hypothesized to have poorer
      neurocognitive functioning than maltreated girls, and nonmaltreated boys and
      girls, in all neurocognitive domains, particularly pertaining to executive
      function and attention. We also examined correlations between cognitive function
      and parent report of child behavior problems for maltreated and nonmaltreated
      children. RESULTS: Maltreated boys performed more poorly on measures of
      intelligence, attention, language, memory, executive function, and academic
      achievement in both reading and math than nonmaltreated boys. Maltreated boys did
      not perform more poorly on these cognitive measures or behavioral measures than
      maltreated girls, except for one memory measure. Maltreated girls performed more
      poorly on measures of intelligence, language, memory, executive function, and
      academic achievement than nonmaltreated girls. Maltreated girls with better
      visual-spatial skills had more internalizing and externalizing problems. Effect
      sizes for these sex differences ranged from small to large. CONCLUSIONS: Both
      maltreated boys and girls showed poorer cognitive function than their
      nonmaltreated sex-matched controls. Maltreated girls had subtle sparing of
      attention and short-term memory (STM). Understanding sex differences in
      neurocognitive functioning may have implications for designing large population
      studies of maltreated youth. (PsycINFO Database Record

PMID- 29199841
TI  - Cumulative effects of the Gulf oil spill and other disasters on mental health
      among reproductive-aged women: The Gulf Resilience on Women's Health study.
AB  - OBJECTIVE: To test whether effects of multiple (up to 5) disasters on mental
      health responses were cumulative (additive effects), or whether an earlier
      disaster produced sensitization (higher) or habituation (lower) responses to a
      later one. METHOD: The Gulf Resilience on Women's Health study interviewed 1,366
      southern Louisiana women regarding their exposure to Hurricanes Katrina, Rita,
      Gustav, and Ike and the Gulf oil spill (measured several ways), and administered
      validated measures of symptoms of depression and posttraumatic stress disorder
      (PTSD). Multiple linear and logistic regression with disaster exposures entered
      singly, combined, and as an interaction were used to model mental health.
      RESULTS: Both exposure to the oil spill and hurricane disaster were associated
      with likely depression and PTSD, consistent with a cumulative model, but we did
      not find statistical interactions that would suggest sensitization or
      habituation. When results were examined with continuous symptom measures of
      depression and PTSD, they were similar, with the exception that exposure to the
      oil spill and experiencing illness or injury because of the hurricane disaster
      showed a significant interaction (p < .05) in a manner consistent with a
      sensitization effect when predicting PTSD symptoms. The results of this study
      point mainly to a cumulative risk for the mental health effects of multiple
      disasters, although some indication of sensitization occurred among those with
      particularly severe experiences. There was no evidence for habituation.
      CONCLUSIONS: These findings may guide efforts to assist those in regions
      experiencing multiple disasters that occur in close sequence. (PsycINFO Database
      Record

PMID- 29199842
TI  - A preliminary survey of pediatricians' experiences with and preferences for
      communication with mental health specialists.
AB  - INTRODUCTION: Pediatricians are more likely than mental health (MH) specialists
      to manage children's MH concerns, and multiple factors complicate their abilities
      to do so adequately. Integrated care initiatives mitigate systems-related
      shortcomings that hamstring MH management in primary care. These initiatives,
      which improve outcomes for adults, are not widespread for youth. Integrated
      health care for children with MH concerns requires regular collaborative
      communication among pediatricians and MH specialists. The nature and quality of
      this communication in typical practice are not fully clear. METHOD: We conducted
      an anonymous pilot survey of 123 pediatric primary care providers from 41 states.
      We examined respondents' experiences with and attitudes about collaborative
      communication barriers and strategies. RESULTS: Respondents estimated that 28% of
      their patients had MH concerns. Nearly 30% reported discomfort treating these
      concerns, 54% described MH care resources in their communities as inadequate, and
      24% of pediatricians reported no communication at all with MH specialists about
      shared patients. Actual contact among communicators was less frequent than
      desired. Satisfaction with communication was low. Barriers to satisfactory
      communication included systems factors, inconsistent/nontimely responses from
      specialists, and the perception that MH specialists are unwilling to communicate.
      DISCUSSION: Many pediatricians appear to view communication with MH specialists
      as less systematic than it ought to be. Efforts to address communication barriers
      may advance integrated care aims and mitigate pediatricians' perceptions of MH
      treatment resource inadequacy. As an important step toward integration, MH
      specialists should consider prioritizing systematic ongoing collaborative
      communication about shared patients. (PsycINFO Database Record

PMID- 29199843
TI  - Motivational interviewing, enhancement, and brief interventions over the last
      decade: A review of reviews of efficacy and effectiveness.
AB  - Motivation is a well-established predictor of recovery for addictive behaviors.
      Treatments aimed at changing substance use and gambling frequently employ
      motivational enhancing strategies, based in the principles of Motivational
      Interviewing (MI). Evidence for these approaches across addictive behaviors does
      not always paint a clear picture. The purpose of this review was to examine
      existing reviews of motivational-based interventions for various substances of
      abuse and gambling in the last decade to gain a deeper understanding of the
      current evidence and implications for future research and clinical practice.
      Literature searches were conducted to identify review articles from January 1,
      2007 to January 30, 2017 for motivational enhancing interventions for alcohol,
      tobacco, drugs, marijuana, cocaine, opioids, methamphetamines, and gambling. Of
      the 144 articles assessed we included a total of 34 review articles in our
      review, including 6 Cochrane reviews. This review supports use of motivationally
      enhancing interventions across addictive behaviors with strongest evidence
      supporting use in alcohol and tobacco, with brief interventions showing strong
      efficacy. There is strong support for MI with marijuana and some support for
      gambling. Insufficient evidence is available for methamphetamine or opiate use.
      There are important caveats. In most cases, MI is more effective than no
      treatment and as effective (but not necessarily more effective) than other active
      treatments. Findings for effectiveness of more intensive motivational
      interventions or combinations are mixed. Treatment fidelity assessments, limited
      subpopulation analyses, and differences in dose, outcomes, and protocol
      specification continue to pose significant problems for reviews. (PsycINFO
      Database Record

PMID- 29199845
TI  - Distinct profiles of information-use characterize identity judgments in children
      and low-expertise adults.
AB  - Face processing abilities vary across the life span: increasing across childhood
      and adolescence, peaking around 30 years of age, and then declining. Despite
      extensive investigation, researchers have yet to identify qualitative changes in
      face processing during development that can account for the observed improvements
      on laboratory tests. The current study constituted the first detailed
      characterization of face processing strategies in a large group of typically
      developing children and adults (N = 200) using a novel adaptation of the Bubbles
      reverse correlation technique (Gosselin & Schyns, 2001). Resultant classification
      images reveal a compelling age-related shift in strategic information use during
      participants' judgments of face identity. This shift suggests a move from an
      early reliance upon high spatial frequency details around the mouth, eye-brow and
      jaw-line in young children (~8 years) to an increasingly more interlinked
      approach, focused upon the eye region and the center of the face in older
      children (~11 years) and adults. Moreover, we reveal that the early versus late
      phases of this developmental trajectory correspond with the profiles of
      information use observed in weak versus strong adult face processors. Together,
      these results provide intriguing new evidence for an important functional role
      for strategic information use in the development of face expertise. (PsycINFO
      Database Record

PMID- 29199846
TI  - Re-examining the influence of attention and consciousness on visual afterimage
      duration.
AB  - The relationship between visual attention and conscious perception has been the
      subject of debate across a number of fields, including philosophy, psychology,
      and neuroscience. Whereas some researchers view attention and awareness as
      inextricably linked, others propose that the two are supported by distinct neural
      mechanisms that can be fully dissociated. In a pioneering study, van Boxtel,
      Tsuchiya, and Koch (2010b) reported evidence for a dissociation between attention
      and conscious perception using a perceptual adaptation task in which
      participants' perceptual awareness and visual attention were manipulated
      independently. They found that participants' awareness of an adapting stimulus
      increased afterimage duration, whereas attending to the adaptor decreased it.
      Given the important theoretical implications of these findings, we endeavored to
      replicate them using an identical paradigm while dealing with some potential
      shortcomings of the original study by adding more trials and a larger participant
      sample. Consistent with van Boxtel, Tsuchiya, and Koch, we found that afterimage
      duration was reliably increased when participants were aware of the adapting
      stimulus. In contrast to the original findings, however, attention to the adaptor
      also increased afterimage duration, suggesting that attention and awareness had
      the same-rather than opposing-effects on afterimage duration. We discuss possible
      reasons for this discrepancy. (PsycINFO Database Record

PMID- 29199844
TI  - A scoping review and meta-analysis of psychosocial and pharmacological treatments
      for cannabis and tobacco use among African Americans.
AB  - The rates of co-occurring cannabis and tobacco use are higher among African
      Americans relative to other racial/ethnic groups. One plausible approach to
      treating co-use among African Americans is to examine the effectiveness of
      treatments for the sole use of cannabis and tobacco to identify effective
      approaches that might be combined to treat the dual use of these substances. The
      current meta-analysis sought to include studies that reported cannabis and/or
      tobacco use outcomes from randomized clinical trials (RCTs) with 100% African
      American samples. A total of 843 articles were considered for inclusion, 29 were
      reviewed by independent qualitative coders, and 22 were included in the review.
      There were no articles on cannabis use treatment with a 100% African American
      sample, resulting in a need to lower the threshold (60%) and conduct a scoping
      review of cannabis studies. Preliminary evidence from a small number of studies
      (k = 7) supports the use of Motivational Interviewing and Cognitive-Behavioral
      Therapy to treat cannabis use among African Americans, but not Contingency
      Management. Results from a meta-analysis of 15 tobacco studies found higher rates
      of smoking abstinence in the treatment condition relative to control conditions
      overall and across short and long-term follow-up periods. Significant differences
      in smoking abstinence were also found when examining the effects of
      pharmacological treatments relative to their control conditions. The clinical and
      research implications of these findings for future psychosocial and
      pharmacological trials for cannabis and tobacco use and co-use among African
      Americans are described. (PsycINFO Database Record

PMID- 29199848
TI  - Characterization of Barium Borate Frameworks Using Raman Spectroscopy.
AB  - Systematic micro-Raman scattering investigations have been carried out on Sm+2
      doped 2(BaO)-n(B2O3) matrices for n = 4, 5, 8, and 2(BaO)-(Na2O)-9(B2O3) using
      the 364 nm excitation of an Ar+ laser. The Raman results have been compared with
      the known structures of barium tetraborate, barium pentaborate, barium
      octaborate, and barium sodium nonaborate. An excellent correlation has been found
      between the BO4/BO3 composition ratios for each product and intensity ratios of
      the designated BO4 and BO3 Raman peaks. Furthermore, the Raman frequencies of
      both BO4 and BO3 groups undergo a systematic blueshift as n increases from four
      to nine. The shift results from a decrease of the B-O bond lengths for both BO4
      and BO3 groups as the samples transition from the tetraborate to nonaborate
      structures. Linear relations (with negative slopes) have been determined between
      the measured Raman frequencies and B-O bond lengths in the frameworks.

PMID- 29199847
TI  - Wnt3a promotes pro-angiogenic features in macrophages in vitro: Implications for
      stroke pathology.
AB  - Wnt3a is implicated in several key cellular processes and its expression has been
      reported in different cell types. Here, we report a novel function for Wnt3a in
      macrophages, whose exposure to this ligand shifts them towards a pro-angiogenic
      phenotype capable, under oxygen and glucose deprivation, of inducing in vitro
      tubular pattern structures in endothelial cells resembling capillary-like
      vasculature. These newly acquired angiogenetic features also include increased
      proliferation and migration and surprisingly, an increase in cell death. This
      work provides a new link between Wnt3a and macrophage-mediated angiogenesis under
      glucose and oxygen deprivation in vitro, which are worth further investigation in
      pathological conditions including stroke, where the stimulation of the angiogenic
      process might help to recovery after tissue injury Impact statement This work
      provides a new link between Wnt3a and macrophage-mediated angiogenesis under
      glucose and oxygen deprivation in vitro. Our results reveal how Wnt3a shifts
      macrophages towards a pro-angiogenic phenotype, which is able-in absence of both
      glucose and oxygen-of inducing angiogenesis in vitro, thus pointing to a synergy
      between the activation of the pathway and the hypoxia scenario. This work also
      demonstrates that modulation of cell death is key in order to explain the
      observed angiogenic effects. We consider all these findings of significant
      importance, since no connection between Wnt3a, macrophages, and angiogenesis has
      been established so far. Furthermore, we do believe that this work provides new
      and interesting results, with Wnt signaling pathway emerging as an interesting
      target mediating beneficial outcomes during the inflammatory response undoubtedly
      linked to stroke pathology, where angiogenesis has been already proposed as a
      potential mechanism to promote recovery after the injury.

PMID- 29199849
TI  - Characterizing the Intrinsic Fluorescence Properties of Historical Painting
      Materials: The Case Study of a Sixteenth-Century Mesoamerican Manuscript.
AB  - Ultraviolet visible (UV-Vis) fluorescence spectroscopy is widely used to study
      polychrome objects and can help to identify the nature of certain materials when
      they present specific fluorescent properties. However, given the complexity of
      the stratified and heterogeneous materials under study, the characterization of
      an intrinsic fluorescence related to a given constituent (a pigment or a binder
      composing a paint layer for example) is not straightforward, and the recorded raw
      data need to be corrected for a number of effects that can influence the detected
      spectral distribution. The application of standard correction procedures to
      experimental fluorescence data gathered on the polychromatic surface of the Codex
      Borbonicus, a 16th-century Aztec manuscript, is described. The results are
      confronted to an alternate new methodology that is based on the hypothesis of
      transparent non-scattering paint layers. This second approach allows to establish
      more clearly the material origin of the detected emission and to discriminate
      apparent fluorescence (emitted by the substrate and transmitted through the paint
      layers) from actual intrinsic emission generated by the coloring materials under
      study. The results show that most of the various emission profiles detected in
      the paint layers of the manuscript actually originate from a unique fluorophore
      (composing the substrate) and should not be used to characterize the coloring
      materials.

PMID- 29199850
TI  - The evolution of minimally invasive cardiac surgery: from minimal access to
      transcatheter approaches.
AB  - The field of minimally invasive cardiac surgery has undergone rapid
      transformation over recent years. In this review, we provide a summary of the
      most current evidence supporting the use of minimally invasive aortic and mitral
      valve replacement techniques, as well as transcatheter approaches for aortic and
      mitral valve disease. As an adjunct, the use of robotically assisted coronary
      bypass surgery and hybrid coronary revascularization procedures is discussed. In
      order to obtain optimal patient outcomes, a collaborative, heart-team approach
      between cardiac surgeons and interventional cardiologists is necessary.

PMID- 29199851
TI  - Feasibility Assessment of Synchronous Fluorescence Spectral Fusion by Application
      to Argan Oil for Adulteration Analysis.
AB  - Synchronous fluorescence spectroscopy (SFS) is used for quantitative analysis as
      well as for qualitative analysis, such as with classification methods. With SFS,
      determination of a useful wavelength interval between the excitation and emission
      wavelengths (Deltalambda) is required. There are a multitude of Deltalambda
      intervals that can be evaluated and optimization of the best one is complex.
      Presented here is a fusion approach for combining Deltalambda intervals, thereby
      negating the need to perform the selection by a skilled operator. To demonstrate
      the feasibility of omitting selection of the best Deltalambda interval,
      adulterated argan oil samples are studied. Argan oil is made from the argan tree,
      endemic to southwestern Morocco, and is well-known for its cosmetic,
      pharmaceutical, and nutritional applications. It is considered a luxury product
      and exported from Morocco around the world. Consequently, detection of argan oil
      adulteration followed by quantitative analysis of the adulterant concentration is
      important. This study uses fusion of SFS spectra obtained at ten Deltalambda
      intervals to first detect adulteration of argan oil by corn oil and then
      determination of the corn oil content. For detection of adulteration, 15 one
      class classification methods were used simultaneously over the ten Deltalambda
      sets of SFS spectra. For tuning parameter dependent classifiers such as
      Mahalanobis distance, non-optimized classifiers are used. Raw classification
      values are used, removing the need to set classifier-dependent threshold values,
      albeit, ultimately, a fusion decision rule is needed for classification. For
      quantitative analysis, two calibration approaches are evaluated with fusion of
      these ten Deltalambda SFS spectral data sets. One is multivariate calibration by
      partial least squares (PLS). The second approach is a univariate calibration
      process where the SFS spectra are summed over respective SFS spectral ranges,
      also known as the area under the curve (AUC). For adulteration detection and
      quantitation of the corn oil, prediction errors decrease with fusion compared to
      individually using the ten Deltalambda interval SFS specific data sets. For this
      argan oil data set, the AUC method generally provides equivalent prediction
      errors to PLS.

PMID- 29199852
TI  - Bleeding with oral anticoagulant dabigatran is highly associated with occult
      cancers in atrial fibrillation patients.
AB  - AIM: The aim of this study was to examine cancer and bleeding in atrial
      fibrillation patients administered with dabigatran. MATERIALS & METHODS: This
      study enrolled 509 consecutive nonvalvular atrial fibrillation patients who
      received dabigatran. The mean administration period was 14.8 +/- 15.7 months. We
      investigated the prevalence and new development of cancers. Further, the relation
      between cancer and adverse events was evaluated. RESULTS: In the 509 patients,
      major bleeding occurred in 2.6% and dyspepsia in 8.4%. Further, 16.9% patients
      had a history of cancer and 3.9% developed new cancers. These adverse events
      developed in 45% patients who developed new cancers. The cancer (hazard ratio:
      6.30; p = 0.003) was a significant predictor of major bleeding. CONCLUSION:
      Bleeding was associated with the presence of cancer.

PMID- 29199853
TI  - Intermittent fasting and cardiovascular disease: current evidence and unresolved
      questions.
AB  - Intermittent fasting has produced a variety of beneficial health effects in
      animal models, although high-quality research in humans has been limited. This
      special report examines current evidences for intermittent fasting in humans,
      discusses issues that require further examination, and recommends new research
      that can improve the knowledge base in this emerging research area. While
      potentially useful for health improvement, intermittent fasting requires further
      study prior to widespread implementation for health purposes. Randomized, longer
      term studies are needed to determine whether using intermittent fasting as a
      lifestyle rather than a diet is feasible and beneficial for the health of some
      members of the human population.

PMID- 29199854
TI  - Costs of subcutaneous and intravenous administration of trastuzumab for patients
      with HER2-positive breast cancer.
AB  - AIM: Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.)
      formulation. The objective of this study was to estimate the costs of
      administration of iv. and sc. trastuzumab treatment. MATERIALS & METHODS: Via
      interviews, we identified all the activities associated with iv. and sc.
      administration. The outcome was time estimates. To estimate the administration
      costs, the time estimates were valued by average gross wages. RESULTS:  The iv.
      administration takes longer time as infusion time is longer (25 or 85 min). The
      iv. administration is associated with higher cost for 17 cycles; ?971 (?1858 vs
      ?887). CONCLUSION: sc. administration is associated with lower administration
      costs. Switching patients from iv. to sc. would make it possible to treat more
      patients without increasing the personnel resources.

PMID- 29199855
TI  - The Hierarchy of Proinflammatory Cytokines in Ocular Inflammation.
AB  - PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated
      in a number of diseases, but it has not been investigated in ophthalmic diseases.
      Here, we evaluated the functional hierarchy of interleukin-1beta (IL-1beta), IL
      6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular
      inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV)
      vectors expressing IL-1beta, IL-6, IL-17A, or TNF intravitreally in naive C57/BL6
      mice and compared and contrasted the inflammatory effects in the eye 5 weeks
      after AAV-mediated gene transfer. We also used an in vitro human system to test
      the effect of cytokines on barrier function. RESULTS: We found that IL-1beta had
      the highest ability to initiate ocular inflammation. The continuous
      overexpression of IL-1beta resulted in a significant upregulation of additional
      proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and
      optical coherence tomography imaging techniques, we showed that a low dose of
      AAVIL-1beta was sufficient and was as pathogenic as a high dose of TNF in
      inducing vascular leakage, retinal degeneration, and cellular infiltration.
      Furthermore, only a marginal increase in IL-1beta was enough to cause cellular
      infiltration, thus confirming the highly pathogenic nature of IL-1beta in the
      eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the
      eye. To examine the clinical relevance of our findings, we used an impedance
      assay to show that IL-1beta alone or TNF alone was able to cause primary human
      retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL
      17A alone had no effect on barrier function; however, in the presence of IL-1beta
      or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects.
      CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of
      proinflammatory cytokines in the eye, and we show that IL-1beta is the most
      pathogenic when it is continuously expressed in the eye.

PMID- 29199856
TI  - Antimicrobial activity of six essential oils against Burkholderia cepacia
      complex: insights into mechanism(s) of action.
AB  - AIM: To investigate the activity and mechanisms of action of six essential oils
      (EOs) against Burkholderia cepacia complex, opportunistic human pathogens highly
      resistant to antibiotics. MATERIALS & METHODS: Minimal inhibitory concentration
      of EOs alone, plus antibiotics or efflux pump inhibitors was determined. RESULTS:
      Origanum vulgare, Thymus vulgaris and Eugenia caryophyllata EOs resulted to be
      more active than the other EOs. EOs did not enhance antibiotic activity against
      the model strain B. cenocepacia J2315. EOs resulted more active in the presence
      of an efflux pump inhibitor acting on Resistance-Nodulation Cell Division efflux
      pumps and against B. cenocepacia J2315 Resistance-Nodulation Cell Division
      knocked-out mutants. CONCLUSION: EOs showed intracellular mechanisms of action
      and, thus, the efflux pumps inhibitor addition could boost their activity.

PMID- 29199857
TI  - Passion, Intimacy, and Commitment in Casual Sexual Relationships in a Canadian
      Sample of Emerging Adults.
AB  - Research on casual sexual relationships (CSRs) among emerging adults is
      prevalent, yet our empirical and theoretical knowledge of relationship processes
      involved in these relationships is limited. The present study's objective was to
      compare four CSR partner types (acquaintance, friend, non-dating partner, ex
      romantic partner) on passion, intimacy, and commitment, the components of
      Sternberg's triangular theory of love. A total of 441 Canadians aged 18-25 years
      who were not in a romantic relationship, and who reported having had more than
      one sexual contact with their last CSR partner, completed an online survey.
      Across all partner types, passion was highest, followed by intimacy and
      commitment. Levels of passion, intimacy, and commitment generally increased with
      partner familiarity. However, CSR partner type differences on the three
      components were partially explained by CSR components (i.e., frequency of sexual
      activity, frequency of social activity, whether partners saw each other with the
      main goal of having sex, sexual exclusivity agreement, and hopes about the
      relationship). Results are consistent with CSRs' emphasis on sexuality, and, to a
      lesser extent, emotions. However, they challenge the mainstream and scientific
      conflation of CSRs with an absence of emotional bond, commitment, or love.

PMID- 29199858
TI  - What do humanitarian emergency organizations do about palliative care? A
      systematic review.
AB  - BACKGROUND: Humanitarian emergency organizations have only recently integrated
      care for non-communicable diseases into their relief action. The needs for
      palliative care in emergencies are still largely unmet. OBJECTIVE: A systematic
      review of health programmes run by international humanitarian organizations that
      take palliative care and/or enhanced pain control into account. METHODS:
      Electronic databases were searched for publications of health programmes
      providing palliative care and/or enhanced pain control in emergency situations.
      Health departments of major international organizations and experts were
      contacted for relevant information. RESULTS: One publication on pain treatment in
      amputees in Freetown, Sierra Leone, fulfilled the selection criteria.
      International humanitarian organizations shared information on their programmes
      in the Democratic Republic of the Congo, Haiti, Kenya and Ukraine/Russia.
      CONCLUSIONS: There is very little information available on palliative care and/or
      enhanced pain control in emergency settings. First programmes have just been
      initiated in the field. More emphasis on sharing experiences and publication
      could accelerate a broader integration of palliative care into humanitarian
      programmes.

PMID- 29199859
TI  - Nutrient Intake and Factors Influencing Eating Behaviors in Older Migrant Women
      Living in the United Kingdom.
AB  - This study examines nutrient intake and factors influencing eating behaviors in a
      sample of 76 migrant older women (>= 60 years) living in the UK. Nutrient intake
      was assessed using a 24-hr recall enhanced by an in-depth probing dietary
      interview. Median energy intake was significantly lower than the UK RNIs (5,125.4
      v. 7,301.1 kJ/d, p < .001). Main nutrients of concern were retinol, vitamin D,
      magnesium, potassium, copper, selenium, and monounsaturated fatty acids.
      Semistructured interviews were conducted with a subsample (n = 46) and analyzed
      using thematic analysis. Although women were knowledgeable about what constitutes
      a healthy diet, factors such as the presence and awareness of obesity and
      noncommunicable diseases, changes to household roles, and dietary restrictions
      related to religious beliefs were identified key influences on participants'
      dietary intake. Strategies targeting this population need to promote not only a
      healthy energy balance, but also dietary adequacy to optimize nutrient intake.

PMID- 29199860
TI  - The value of gamma glutamyltransferase in predicting myocardial infarction in
      patients with acute coronary syndrome.
AB  - AIM: To assess the utility of gamma-glutamyl transferase (GGT) and C-reactive
      protein (CRP) in predicting troponin elevation in patients with acute coronary
      syndrome. PATIENTS: The total of 119 patients were divided into troponin-positive
      (n = 61) and troponin-negative (n = 58) patients. RESULTS: CRP cut-off value
      >=13.4 mg/l had the sensitivity of 68.1% and specificity of 62.5%, while the GGT
      cut-off value >=61.5 IU/l had the sensitivity of 66.0% and specificity of 62.0%
      and combined use of both CRP and GGT had 71.4% sensitivity and 69.6% specificity
      in predicting troponin increase in acute coronary syndrome patients. CONCLUSION:
      GGT might be used as an adjuvant marker for risk assessment patients who present
      with chest pain and are suspected to have acute coronary syndrome.

PMID- 29199861
TI  - Stenting the complex patent ductus arteriosus in tetralogy of Fallot with
      pulmonary atresia: challenges and outcomes.
AB  - Patent ductus arteriosus (PDA) stenting has gained acceptance for palliation in
      cyanotic congenital heart disease. The PDA in tetralogy of Fallot with pulmonary
      atresia (ToF-PA) arises, in the left aortic arch, from underneath the arch and
      connects to the proximal left pulmonary artery, often resulting in stenosis. The
      PDA is usually elongated and tortuous, making stent implantation challenging.
      Shorter duration of palliation, aggravation of branch pulmonary artery stenosis
      resulting in poor growth and difficulty at surgery makes ductal stenting
      controversial. Access via the carotid and axillary artery reduces complexity of
      the procedure and improves success, with recent data demonstrating good pulmonary
      artery growth. Advances in bioresorbable stents offer future promise and will
      likely resolve some controversies surrounding PDA stenting in ToF-PA.

PMID- 29199862
TI  - Expression of SIRT1 and P53 in Rat Lens Epithelial cells in Experimentally
      Induced DM.
AB  - PURPOSE: To determine the etiopathogenesis of diabetic cataract by studying
      changes in relative expressions of silent information regulator protein-1 (SIRT1)
      and P53 in rat lens epithelial cells (LECs) in experimentally induced diabetes
      mellitus (DM). METHODS: Six-week-old male SD rats (n = 120) were randomly divided
      into experimental (n = 80 rats) and control (n = 40 rats) groups. DM was induced
      in the experimental group (diabetic model) by intraperitoneal (i.p.) injection of
      60 mg/kg streptozotocin (STZ). Control group rats were injected similarly with
      phosphate-buffered saline (PBS). Four and eight weeks after successful induction
      of DM, relative expressions of SIRT1 and P53 in LECs were analyzed using
      quantitative real-time (qRT) fluorescence polymerase chain reaction (qRT-PCR) and
      Western blot analysis. RESULTS: Expression of both SIRT1 and P53 was observed in
      LECs of control and experimental group rats at 4 and 8 weeks but was
      significantly greater in experimental compared with control group rats (p <
      0.05). CONCLUSIONS: Expression of both SIRT1 and P53 increases in the early
      stages of diabetic cataract formation, indicating that they play potentially
      important roles in the pathogenesis of diabetic cataract.

PMID- 29199863
TI  - Optical Coherence Tomography-Based Scattering Properties of Retinal Vessels in
      Glaucoma Patients.
AB  - PURPOSE: Clinical trials have demonstrated that retinal blood flow deficiencies
      are present in patients with open-angle glaucoma (OAG). We introduce a method for
      facilitating retinal vessel analysis: The intensity of the distal shadow of
      vessels in optical coherence tomography (OCT) caused by the scattered signal is
      analyzed, compared between healthy subjects and OAG patients and correlated with
      OCT angiography (OCT-A) flow density. PATIENTS AND METHODS: We recruited 80
      patients with diagnosed OAG (mean age 63.4 +/- 13.2 years) and 80 healthy age
      matched control subjects for comparison, and 20 patients for the correlation with
      OCT-A flow density. Patients received perimetry, peripapillary OCT measurements,
      and selected patients OCT-A of the papillary area. The vessel shadow intensity
      (VSI) is based on peripapillary OCT scans: the intensity of the distal vessel
      shadow was automatically compared to its surroundings, separated by arteries and
      veins. Flow density of the OCT-A scan was calculated by binarization and
      quantification of the pixel density. RESULTS: The VSI for arteries was in OAG
      patients with 7.52 +/- 2.62 [%] significantly lower compared to healthy subjects
      (9.03 +/- 3.38 [%], p = 0.0029). In veins, the VSI was as well significantly
      lower for OAG patients (14.9 +/- 3.59 [%]) compared to healthy subjects (17.46 +/
      4.45 [%], p < 0.0001). Furthermore, in OAG patients there was a significant
      correlation of mean deviation of the visual field results with the veins' VSI (p
      = 0.0006; r = -0,454). There was no significant correlation of scattering
      properties with OCT-A flow density (p > 0.05). CONCLUSIONS: We conclude that the
      OCT-based analysis of the scattering properties of retinal vessels differs
      significantly between patients with OAG and healthy subjects. Furthermore,
      changes in the scattering properties of veins correlated with the stage of the
      disease in terms of visual field deficits. These properties might complement
      existing measurements of ocular blood flow including OCT-A flow density.

PMID- 29199864
TI  - Intracameral Use of Nepafenac: Safety and Efficacy Study.
AB  - PURPOSE: To test the intracameral safety of nepafenac and its efficacy in
      inhibiting prostaglandin synthesis during phacoemulsification surgery. METHODS:
      The safety evaluation was conducted in normal eyes of rabbits, 0.1ml of 0.3% and
      1% nepafenac was injected intracamerally. Extensive studies to detect adverse
      response ranged from a gross examination of eyes under slit lamp biomicroscope,
      fluorescein dye test, Schirmer tear test, test for corneal sensitivity,
      intraocular pressure measurement (IOP), specular microscopy,
      electroretinography(ERG), and histopathological examination of intraocular
      tissues. Efficacy of nepafenac was studied by intracameral injection of 0.1%,
      0.3% nepafenac, nepafenac 0.3%+1% lignocaine, and 1% lignocaine alone, before
      phacoemulsification surgery and intraoperative mydriasis along with
      PGE2(ProstaglandinE2) secretion were recorded. RESULTS: Single 0.1ml of 0.3% or
      1% nepafenac did not significantly (p > 0.05) alter physiological parameters and
      histology of cornea, iris, and retina. Nepafenac 0.3% effectively inhibited PGE2
      secretion. No significant (p > 0.05) prevention of miosis was recorded with 0.1%
      or 0.3% nepafenac. However, a combination of 0.3% nepafenac + 1% lignocaine and
      1% lignocaine alone significantly (p < 0.05) arrested miosis during the
      intraoperative period. CONCLUSION: An intracameral concentration of up to 1%
      nepafenac does not adversely affect the rabbit eye. Nepafenac fails to prevent
      miosis but inhibits prostaglandin release during phacoemulsification surgery.

PMID- 29199865
TI  - Changes in the Meibomian Gland After Exposure to Intense Pulsed Light in
      Meibomian Gland Dysfunction (MGD) Patients.
AB  - PURPOSE: To observe (1) changes in meibomian gland (MG) after exposure to intense
      pulsed light (IPL) and (2) to understand the mechanism by which IPL treats
      meibomian gland dysfunction (MGD) in patients. METHODS: A cohort study, including
      35 MGD patients, was conducted. IPL treatment was administered in one group (IPL
      group; n = 18), and eyelid hygiene in another (control group; n = 17) for 3
      months. All patients were given artificial tears during the treatment period.
      Associated ocular-surface indexes (ocular surface disease index, OSDI; tear
      breakup time, TBUT, Schirmer 1Test, corneal staining, and conjunctival staining),
      MG function, MG macro-morphology, and MG micro-morphology were examined before
      and after treatment. The relationships between the change in symptom score and
      the change in the other indexes (related ocular-surface indexes, MG functional
      indexes, and MG morphological indexes) were evaluated. RESULTS: There was no
      statistical difference in pretreatment between the IPL and the control groups in
      terms of age, gender, related medical history, MGD stage, and all examined
      indexes, with the exception of conjunctival staining. OSDI, TBUT, meibum quality,
      MG expressibility, and MG dropout improved after treatment in both of the two
      groups (all P < 0.05). The MG microstructure indexes, including the MG acinar
      longest diameter (ALD), MG acinar unit density (AUD), and the positive rate of
      inflammatory cells (ICs) around glandular structures were significantly improved
      in the IPL group. No improvements of microstructure were found in the control
      group. CONCLUSION: IPL treatment improves the symptom score of patients,
      associated ocular-surface indexes, MG function, and MG macrostructure as well as
      eyelid hygiene. And IPL treatment particularly improves MG microstructure and
      decreases MG inflammation in MGD patients.

PMID- 29199866
TI  - The Association of Single-Nucleotide Polymorphisms in the MMP-9 Gene with Normal
      Tension Glaucoma and Primary Open-Angle Glaucoma.
AB  - PURPOSE: To evaluate the association of matrix metalloproteinases (MMP)-9 gene
      polymorphisms with normal tension glaucoma (NTG) and primary open-angle glaucoma
      (POAG) in the South Korean population. MATERIALS AND METHODS: A total of 700
      South Korean subjects were recruited: 146 patients with NTG, 174 patients with
      POAG, and 380 healthy adults. Five single-nucleotide polymorphisms (SNPs;
      rs3918429, rs2274755, rs3787268, rs3918261, and rs3918270) of MMP-9 were analyzed
      in all subjects. The association with each disease was tested using an allelic
      chi2 test and p values were corrected by permutation tests with 100 000
      permutations. RESULTS: Among the five SNPs, rs2274755 showed a significant
      association with NTG (p = 0.021). The T allele of rs2274755 had an allelic odds
      ratio of 1.67 (95% confidence interval, 1.12-2.50). The association remained
      significant after correction using permutation tests (p = 0.039). It was also
      significant in an association analysis for genotype frequency (p = 0.011). The
      SNP was predicted to be found within a splicing site and a conserved region. No
      SNPs analyzed were significantly associated with POAG (p > 0.05). CONCLUSIONS:
      The rs2274755 SNP in the MMP-9 gene was significantly associated with NTG. This
      supports a possible role of the MMP-9 gene in NTG pathogenesis.

PMID- 29199867
TI  - Relevance of Global Health Security to the US Export Economy.
AB  - To reduce the health security risk and impact of outbreaks around the world, the
      US Centers for Disease Control and Prevention and its partners are building
      capabilities to prevent, detect, and contain outbreaks in 49 global health
      security priority countries. We examine the extent of economic vulnerability to
      the US export economy posed by trade disruptions in these 49 countries. Using
      2015 US Department of Commerce data, we assessed the value of US exports and the
      number of US jobs supported by those exports. US exports to the 49 countries
      exceeded $308 billion and supported more than 1.6 million jobs across all US
      states in agriculture, manufacturing, mining, oil and gas, services, and other
      sectors. These exports represented 13.7% of all US export revenue worldwide and
      14.3% of all US jobs supported by all US exports. The economic linkages between
      the United States and these global health security priority countries illustrate
      the importance of ensuring that countries have the public health capacities
      needed to control outbreaks at their source before they become pandemics.

PMID- 29199868
TI  - Entry Body Mass and Earnings: Once Penalized, Ever Penalized?
AB  - It has previously been reported that an individual's body mass index (BMI)
      contemporaneously penalizes wages for women, but has no effect and sometimes
      rewards wages for men. In young adults, we estimate the association of BMI status
      with initial wages to assess whether initial BMI at the beginning of an
      individual's career affects initial and later earnings. We pooled data from 388
      men and 305 women, aged 20-40 years, with BMI information for the first year of
      employment, using the Korean Labor and Income Panel Study. A labor market penalty
      for a higher BMI among women was found only for overweight or obese segments,
      particularly those with relatively higher monthly wages. Meanwhile, a higher BMI
      in underweight or normal weight segments could reward employment probability for
      women and monthly wages for men. Such rewards of relatively higher monthly wages
      were also estimated for men in the overweight segment. Our findings suggest
      discrimination as one factor penalizing higher BMI in the labor market.

PMID- 29199869
TI  - "Inflammaging" and Estradiol among Older U.S. Women: A Nationally Representative
      Longitudinal Study.
AB  - Despite accumulating small-sample and clinical evidence on "inflammaging," no
      population-representative longitudinal studies have specifically examined women's
      late-life inflammation trends. While a range of studies indicates estradiol's
      immunomodulation role, evidence is contradictory on whether its effects are pro-
      or antiinflammatory among older women. Using longitudinal data from the first two
      waves of the National Social Life, Health and Aging Project-a national
      probability sample of older U.S. adults aged 57 to 85 years at baseline-this
      study began to fill these gaps. Findings suggested rather than being a lifelong
      process, older women's inflammaging may have a biological window that closes with
      senescence. Moreover, their endogenous estradiol plays a proinflammatory rather
      than immunoprotective role. Nor does this sex steroid modulate age effects on
      women's inflammation. More sex-specific basic research is needed on causal
      mechanisms underlying women's late-life inflammaging patterns.

PMID- 29199870
TI  - Spiritual Struggles and Interleukin-6: Assessing Potential Benefits and Potential
      Risks.
AB  - The purpose of this study is to evaluate the relationship between spiritual
      struggles and levels of interleukin-6 (IL-6) with a subsample (N = 943) of
      participants who took part in a nationwide survey. This study, which was
      completed in 2014, was conducted in the United States. Spiritual struggles refer
      to difficulties that a person may encounter with his or her faith and include
      having a troubled relationship with God, encountering difficulties with religious
      others, and being unable to find a sense of ultimate meaning in life. Based on
      the notion that spiritual struggles may be associated with personal growth as
      well physical health problems, it was hypothesized that there is a nonlinear
      relationship between the two: levels of IL-6 will decline at relatively low
      levels of spiritual struggles, but levels of IL-6 will increase as spiritual
      struggles become more severe. The findings support this hypothesis and suggest
      there is a quadratic relationship between spiritual struggles and IL-6. The
      clinical implications of these findings are discussed.

PMID- 29199871
TI  - Perceived Racial Discrimination in the Workplace and Body Weight among the
      Unemployed.
AB  - This study investigates the association between body weight and the likelihood
      that people perceive that they have been the victims of racial discrimination in
      the workplace among the unemployed. I find that unemployed obese men and women
      are 8.4 percentage points and 7.7 percentage points, respectively, more likely to
      have experienced racial discrimination before becoming unemployed than their non
      obese counterparts. For unemployed men, the relationship between body weight and
      perceived racial discrimination does not seem to be associated with race. For
      unemployed women, being black and obese significantly increases the likelihood of
      perceiving racial discrimination.

PMID- 29199872
TI  - Inflammation and Cognition in Older Adults: Evidence from Taiwan.
AB  - Inflammation has been linked to clinical cognitive impairment, including
      Alzheimer's disease. Less is known, however, about the relationship between
      inflammation and normal, age-associated cognitive decline. An understanding of
      the determinants of all types of cognitive decline is important for improving
      quality of life in an aging world. This study investigated whether biomarkers of
      inflammation were associated with cognitive function and decline in older
      Taiwanese adults. Data were from the Taiwan Longitudinal Study of Aging and the
      Social Environment and Biomarkers of Aging Study. Inflammation was measured in
      2000 and 2006 as C-reactive protein, interleukin-6, soluble e-selectin, soluble
      intercellular adhesion molecule-1, and white blood cell count. Cognition was
      assessed by 10 cognitive and memory tasks, measured in 2006, 2007, and 2011.
      Growth curve models were used to examine the relationship between inflammation
      and cognitive score over this time period. Higher levels of inflammation were
      associated with lower baseline cognitive scores, but not with longitudinal change
      in cognitive score. This study did not support a causal link between inflammation
      and cognitive decline among this older cohort. The observed cross-sectional
      relationship could reflect a causal relationship that arises earlier in life, or
      confounding; additional research across the life course is warranted.

PMID- 29199873
TI  - Disposition of toxic drugs and chemicals in man 11th edition.

PMID- 29199874
TI  - Necrostatin-1 attenuates lipopolysaccharide-induced acute lung injury in mice.
AB  - AIM OF THE STUDY: Receptor-interacting protein (RIP) kinase family members are
      involved in several biological processes. However, their role in acute lung
      injury (ALI) is still unclear. In the present study, we aim to determine the
      expression and function of RIP kinase family in ALI. MATERIALS AND METHODS: In
      the present study, ALI was induced in BALB/c male mice by intravenously injecting
      lipopolysaccharide (LPS). The expression levels of the RIP kinase family in ALI
      mice were determined using western blotting and immunohistochemical staining. The
      specific RIP-1 inhibitor, necrostatin-1, was used to treat LPS-induced ALI mice,
      followed by survival time recording, as well as histopathological and
      immunohistochemical staining of lung tissues, western blotting, myeloperoxidase
      (MPO) assay and enzyme-linked immunosorbent assay (ELISA) of related cytokines
      and downstream target expression. RESULTS: We found that RIP-1 expression was
      upregulated in the lung of ALI mice and inhibition of RIP-1 by necrostatin-1
      significantly prolonged the survival time of mice, which was accompanied by less
      serve lung injury. Furthermore, lower expression of pro-inflammatory cytokines
      (interleukin [IL]-6, tumor necrosis factor [TNF]-alpha, IL-8, cyclooxygenase
      [COX]-2, monocyte chemoattractant protein [MCP]-1, and IL-1beta), MPO and nuclear
      factor (NF)-kappaB activation were found in bronchoalveolar lavage fluid (BALF)
      and lung tissues of necrostatin-1-treated ALI mice. Necrostatin-1 also attenuated
      LPS-induced pro-inflammatory cytokine expression and NF-kappaB activation in RAW
      264.7 cells. CONCLUSIONS: In summary, necrostatin-1 protected against LPS-induced
      ALI in mice by inhibiting inflammation and pulmonary NF-kappaB activation. Thus,
      necrostatin-1 could be a novel therapeutic strategy for ALI.

PMID- 29199875
TI  - Using positron emission tomography to investigate hormone-mediated neurochemical
      changes across the female lifespan: implications for depression.
AB  - Ovarian hormones, particularly oestrogen and progesterone, undergo major
      fluctuations across the female lifespan. These hormone transition periods, such
      as the transition from pregnancy to postpartum, as well as the transition into
      menopause (perimenopause), are also known to be times of elevated susceptibility
      to depression. This study reviews how these transition periods likely influence
      neurochemical changes in the brain that result in disease vulnerability. While
      there are known associations between oestrogen/progesterone and different
      monoaminergic systems, the interactions and their potential implications for mood
      disorders are relatively unknown. Positron Emission Tomography (PET) allows for
      the in-vivo quantification of such neurochemical changes, and, thus, can provide
      valuable insight into how both subtle and dramatic shifts in hormones contribute
      to the elevated rates of depression during pre-menstrual, post-partum, and
      perimenopausal periods in a woman's life. As one better understands how to
      address the challenges of PET studies involving highly vulnerable populations,
      such as women who have recently given birth, one will gain the insight necessary
      to design and individualize treatment and therapy. Understanding the precise time
      line in younger women when dramatic fluctuations in the hormonal milieu may
      contribute to brain changes may present a powerful opportunity to intervene
      before a vulnerable state develops into a diseased state in later life.

PMID- 29199876
TI  - Perceived factors influencing hospital-based primary care clinic referrals to
      community health medical nutrition therapy: An exploratory study.
AB  - Primary care clinics provide an array of diagnostic and clinical services that
      assist patients in preventing the onset or managing acute and chronic conditions.
      Some chronic conditions such as high blood pressure, high cholesterol, and type 2
      diabetes require primary care professionals to seek additional medical
      intervention from registered dieticians. This study explored beliefs, attitudes,
      and practices of medical and administrative professionals in primary care clinics
      encountering patients who are potential candidates for ongoing nutrition
      education or counselling. Five focus groups with primary care providers and
      clinical staff (n = 24) were conducted to identify perceived intra-organisational
      factors influencing initiation of community health medical nutrition therapy
      (MNT) referrals. Lack of clarity regarding community health dieticians' role in
      chronic disease management was the primary finding for the absence of MNT
      referrals. Insurance-imposed constraints, perceived patient readiness to change,
      and service inaccessibility were revealed as barriers that influence referrals to
      both community health and specialty care dieticians. This study underscores the
      importance of identifying organisational and interpersonal barriers that
      influence the initiation of community health MNT referrals. Understanding these
      barriers can create stronger interprofessional collaboration between primary care
      providers and community health dieticians.

PMID- 29199878
TI  - Do We Expect Women to Look Happier Than They Are? A Test of Gender-Dependent
      Perceptual Correction.
AB  - Feminine facial features enhance the expressive cues associated with happiness
      but not sadness. This makes a woman look happier than a man even when their
      smiles have the same intensity. So, to correctly infer the actual happiness of a
      woman, one would have to subtract the effect of these facial features. We
      hypothesised that our perceptual system would apply this subtraction for women,
      but not for men. This implies that this female-specific subtraction would cause
      one to infer a man to be happier than a woman if both are matched for facial
      appearance and expression intensity. We tested this using androgynous virtual
      faces with equal expression intensity. As predicted, happy men were inferred to
      be happier than happy women, but sad men were not inferred to be sadder than sad
      women, supporting our hypothesis of a gender- and emotion-specific perceptual
      correction.

PMID- 29199877
TI  - The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler
      reinjection after hyaluronidase injection.
AB  - BACKGROUND: Hyaluronidase injection is a commonly performed treatment for
      overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients
      often wants the HA filler reinjection after the use of hyaluronidase, though the
      optimal timing of reinjection of HA filler still remains unknown. OBJECTIVES: To
      provide the optimal time interval between hyaluronidase injections and HA filler
      reinjections. METHODS: 6 Sprague-Dawley rats were injected with single monophasic
      HA filler. 1 week after injection, the injected sites were treated with
      hyaluronidase. Then, HA fillers were reinjected sequentially with differing time
      intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA
      filler, all injection sites were excised for histologic evaluation. RESULTS: 3
      hours after reinjection of HA filler, the appearance of filler material became
      evident again, retaining its shape and volume. 6 hours after reinjection, the
      filler materials restored almost its original volume and there were no
      significant differences from the positive control. CONCLUSIONS: Our data suggest
      that the hyaluronidase loses its effect in dermis and subcutaneous tissue within
      3-6 hours after the injection and successful engraftment of reinjected HA filler
      can be accomplished 6 hours after the injection.

PMID- 29199880
TI  - Exposure to cigarette smoke extract and lipopolysaccharide modifies cytoskeleton
      organization in bronchial epithelial cells.
AB  - The integrity of the respiratory epithelium is crucial for airway homeostasis.
      Tobacco smoke exposure and recurrent infections of the airways play a crucial
      role in the progression and in the decline of the respiratory function in chronic
      obstructive pulmonary disease (COPD). The aim of this study was to detect
      differentially expressed proteins in a bronchial epithelial cell line (16-HBE)
      stimulated with cigarette smoke extract (CSE) and lipopolysaccharide (LPS), a
      constituent of gram-negative bacteria, alone and/or in combination, by using two
      dimensional electrophoresis (2DE) analysis coupled with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Western blot analysis was
      applied to confirm the expression of significantly modulated proteins. Flow
      cytometry and immunofluorescence were used to assess F-actin polimerization by
      phalloidin method. Fourteen proteins, with significant (p < 0.05) changes in
      intensity, were identified at various experimental points: 6 were up-regulated
      and 8 were down-regulated. As expected, bioinformatic analysis revealed that most
      of these proteins are involved in anti-oxidant and immune responses and in
      cytoskeleton stability. Western blot analysis confirmed that: Proteasome
      activator complex subunit 2 (PSME2), Peroxiredoxin-6 (PRDX6), Annexin A5 (ANXA5)
      and Heat shock protein beta-1 (HSPB1) were reduced and Coactosin-like protein
      (COTL-1) was increased by co-exposure of CSE and LPS. Furthermore, LPS and CSE
      increased actin polimerization. In conclusion, although further validation
      studies are needed, our findings suggest that, CSE and LPS could contribute to
      the progressive deterioration of lung function, altering the expression of
      proteins involved in metabolic processes and cytoskeleton rearrangement in
      bronchial epithelial cells.

PMID- 29199881
TI  - Phytochylomicron as a dual nanocarrier for liver cancer targeting of luteolin: in
      vitro appraisal and pharmacodynamics.
AB  - AIM: A novel luteolin (LUT) loaded dual bionanocarrier 'phytochylomicron' was
      elaborated to allow LUT injectable delivery and liver cancer targeting. METHODS:
      LUT-phospholipid complex was prepared and loaded into chylomicron nanocarrier.
      Then phytochylomicron underwent physicochemical characterization, cell culture
      and pharmacodynamics studies on a new liver-tumor model. RESULTS:
      Phytochylomicron showed sustained release pattern with minimum drug leakage until
      reaching the liver. Cell culture studies showed high growth inhibition of Hep G2
      cells with 2.6-fold enhancement in cellular uptake. Pharmacodynamics demonstrated
      enhanced tumor growth inhibition (sixfold) with a significant tumor size
      reduction. Finally, cell culture results demonstrated an excellent correlation
      with pharmacodynamics confirming the obtained findings. CONCLUSION: A novel
      phytochylomicron nanosystem was successfully elaborated with promising
      characteristics that promoted injectable LUT delivery and liver cancer targeting.
      [Formula: see text].

PMID- 29199882
TI  - Association Study of MECP2 Gene Single Nucleotide Polymorphisms in Juvenile-Onset
      Systemic Lupus Erythematosus Patients from Iran.
AB  - INTRODUCTION: Juvenile-onset systemic lupus erythematosus is a multigenic
      autoimmune disorder. Polymorphisms of MECP2 gene have been reported to increase
      the risk of adult-onset SLE. In this study, we aimed to analyze if MECP2 gene
      polymorphisms could impress the proneness to JSLE in Iranian population. MATERIAL
      AND METHODS: Polymorphisms of MECP2 gene were genotyped in 50 Iranian JSLE
      patients and 426 matched healthy controls employing the real-time PCR allelic
      discrimination technique. RESULTS: None of the alleles and genotypes of MECP2
      gene SNPs had significantly different distribution between patients and controls.
      The CTAT haplotype was represented more frequently and significantly in JSLE
      cases than in controls. A strong linkage disequilibrium was observed among the
      variants. CONCLUSIONS: Although adult-onset SLE had been associated with MECP2
      gene variants, this gene is not associated with disease susceptibility in JSLE
      patients, implying the involvement of different susceptibility genes in the
      pathogenesis of SLE and JSLE.

PMID- 29199883
TI  - Death from a driverless vehicle.
AB  - Road traffic accidents are a major cause of fatalities around the world, and a
      number of deaths are caused by moving traffic on public roads. Deaths from
      vehicles that are off the highway may be called non-traffic fatalities which can
      be due to a vehicle reversing, carbon monoxide poisoning, weather-induced over
      heating inside the vehicle and electric windows. Children (and animals) are the
      usual victims. We report a case from India where a man was found lying dead by
      the roadside with a lorry nearby. The autopsy findings indicated that he had been
      run over, but as there was no history of a vehicular collision and with no
      eyewitnesses, the investigators were unsure of the probable sequence of events
      that led to his death. The autopsy findings, history, circumstantial evidence and
      chemical analysis enabled us to work out what had happened.

PMID- 29199884
TI  - Congenital cavitary optic disc anomaly and Axenfeld's anomaly in Wolf-Hirschhorn
      syndrome: A case report and review of the literature.
AB  - BACKGROUND: Wolf-Hirschhorn syndrome is a rare genetic syndrome caused by a
      heterozygous deletion on chromosome 4p16.3 and is characterized by a "Greek
      warrior helmet" facies, hypotonia, developmental delay, seizures, structural
      central nervous system defects, intrauterine growth restriction, sketelal
      anomalies, cardiac defects, abnormal tooth development, and hearing loss. A
      variety of ocular manifestations may occur in up to 40% of patients.
      MATERIALS/METHODS: We report the genetic testing results, systemic findings, and
      complete ophthalmologic examination findings in a patient with Wolf-Hirschhorn
      syndrome, including external photography, RetCam3 (Clarity Medical Systems,
      Pleasonton, CA) goniography, and fundus photography. In addition, we review the
      literature on ocular manifestations of Wolf-Hirschhorn syndrome. RESULTS:
      Microarray analysis revealed an unbalanced translocation between 4p16.3-15.3 and
      Xp22.33-p22.2. Systemic findings included "Greek warrior helmet" facies,
      hypotonia, cleft palate, neonatal tooth eruption, talipes equinovarus, bilateral
      clinodactyly, clitoromegaly, partial agenesis of the corpus callosum, bilateral
      renal hypoplasia, and two atrial septal defects. Ocular findings included normal
      intraocular pressures and corneal diameters, large-angle exotropia, downward
      slanting of the palpebral fissures, absent eyelid creases, upper and lower eyelid
      retraction with shortage of the anterior eyelid lamellae, euryblepharon,
      lagophthalmos with poor Bell's reflex and exposure keratopathy, hypertelorism,
      Axenfeld's anomaly, megalopapillae, and cavitary optic disc anomaly. CONCLUSIONS:
      We describe the ocular phenotype of a patient with Wolf-Hirschhorn syndrome,
      including the rare descriptions and photographs of Axenfeld's anomaly,
      megalopapilla, and cavitary optic disc anomaly in this condition.

PMID- 29199885
TI  - Emergency Medical Services Provider Experiences of Hospice Care.
AB  - BACKGROUND: Growing numbers of emergency medical services (EMS) providers respond
      to patients who receive hospice care. The objective of this investigation was to
      assess the knowledge, attitudes, and experiences of EMS providers in the care of
      patients enrolled in hospice care. METHODS: We conducted a survey study of EMS
      providers regarding hospice care. We collected quantitative and qualitative data
      on EMS provider's knowledge, attitudes, and experiences in responding to the care
      needs of patients in hospice care. We used Chi-squared tests to compare EMS
      provider's responses by credential (Emergency Medical Technician [EMT] vs.
      Paramedic) and years of experience (0-5 vs. 5+). We conducted a thematic analysis
      to examine open-ended responses to qualitative questions. RESULTS: Of the 182 EMS
      providers who completed the survey (100% response rate), 84.1% had cared for a
      hospice patient one or more times. Respondents included 86 (47.3%) EMTs with
      Intermediate and Advanced training and 96 (52.7%) Paramedics. Respondent's years
      of experience ranged from 0-10+ years, with 99 (54.3%) providers having 0-5 years
      of experience and 83 (45.7%) providers having 5+ years of experience. There were
      no significant differences between EMTs and Paramedics in their knowledge of the
      care of these patients, nor were there significant differences (p < 0.05) between
      those with 0-5 and 5+ years of experience. Furthermore, 53 (29.1%) EMS providers
      reported receiving formal education on the care of hospice patients. A total of
      36% respondents felt that patients in hospice care required a DNR order. In EMS
      providers' open-ended responses on challenges in responding to the care needs of
      hospice patients, common themes were family-related challenges, and the need for
      more education. CONCLUSION: While the majority of EMS providers have responded to
      patients enrolled in hospice care, few providers received formal training on how
      to care for this population. EMS providers have expressed a need for a formal
      curriculum on the care of the patient receiving hospice.

PMID- 29199886
TI  - Mycosynthesis of bactericidal silver and polymorphic gold nanoparticles:
      physicochemical variation effects and mechanism.
AB  - AIM: Extracellular synthesis of silver and gold nanoparticles using aqueous cell
      free filtrate (CFF) of endophytic Chaetomium globosum and characterization of its
      bioactive proteins. METHODS: Temperature and pH gradients were used to assess
      their effects on dimensions of NPs. NPs were tested in vivo for antibacterial
      activity. MALDI-TOF-MS/MS was used for characterization of CFF proteins. RESULTS:
      Fungal CFF fabricated nanoparticles of various shape under varied physicochemical
      conditions. Silver nanoparticles showed significantly (p <= 0.5) enhanced
      antibacterial activity against Staphylococcus aureus and Klebsiella pneumoniae
      compared with AgNO3. Two prominent CFF proteins showed homology with benzoate 4
      monooxygenase cytochrome P450 and ubiquinol-cytochrome c reductase. CONCLUSION:
      The study achieved controlled mycosynthesis of NPs and explains the hitherto
      poorly known mechanism of reduction, stabilization and antibacterial activity of
      nanoparticles.

PMID- 29199887
TI  - The inflammatory response to silver and titanium dioxide nanoparticles in the
      central nervous system.
AB  - Despite the increasing number of neurotoxicological studies on metal-containing
      nanoparticles (NPs), the NP-induced neuroinflammation has not yet been well
      understood. This review provides a comprehensive understanding of inflammatory
      responses to two typical metal-containing NPs, namely silver NPs (Ag-NPs) and
      titanium dioxide NPs (TiO2-NPs). Ag-NPs and TiO2-NPs could translocate into the
      CNS through damaged blood-brain barrier, nerve afferent signaling and eye-to
      brain ways, and even cell uptake. NPs could stimulate the activation of glial
      cells to release proinflammatory cytokines and generate reactive oxygen species
      and nitric oxide production, resulting in the neuroinflammation. The potential
      mechanisms of Ag-NPs and TiO2-NPs causing inflammation are complex, including
      several immune response relevant signaling pathways. Some parameters governing
      their ability to cause neuroinflammation are presented as well.

PMID- 29199888
TI  - A High-Sensitivity, Microtiter-Based Plate Assay for Plant Pattern-Triggered
      Immunity.
AB  - The first step in the plant immune response to pathogen challenge involves the
      perception of conserved epitopes, called microbe-associated molecular patterns
      (MAMPs), by cell-surface pattern recognition receptors (PRRs). Given the key
      roles that MAMPs and PRRs play in plant innate immunity, great effort has been
      expended to identify these molecules. Current methods for assaying these immune
      responses are often limited in their resolution and throughput, and consequently,
      there is a need for medium- to high-throughput methodologies. Here, we describe
      the development of a 96-well microtiter plate-based assay for plant pattern
      triggered immunity that measures the activity of plant peroxidase (POX) enzymes
      produced in response to treatment with bacterial MAMPs. The system has been
      optimized to minimize both the amount of plant tissue and MAMPs required and
      displays up to three orders of magnitude greater sensitivity than the traditional
      luminol-based reactive oxygen species assay when measuring the plant response to
      treatment with the bacterial MAMP flg22, reaching detection limits in the
      picomolar range. This high sensitivity opens the possibility of evaluating the
      immune-eliciting effects of weaker elicitors. The throughput and material
      requirements of the assay make it ideal for screens involving quantitative
      measurement of the plant innate immune response to MAMPs.

PMID- 29199889
TI  - Polysaccharide Peptide-Induced Virus Resistance Depends on Ca2+ Influx by
      Increasing the Salicylic Acid Content and Upregulating the Leucine-Rich Repeat
      Gene in Arabidopsis thaliana.
AB  - Plant viral diseases cause severe economic losses in agricultural production. The
      development of biosource-derived antiviral agents provides an alternative
      strategy to efficiently control plant viral diseases. We previously reported that
      the exogenous application of polysaccharide peptide (PSP) exerts significant
      inhibitive effects on Tobacco mosaic virus infection in Nicotiana tabacum. In
      this study, we studied in additional detail the mechanism by which PSP can induce
      virus resistance in Arabidopsis thaliana. We found that PSP significantly induced
      Ca2+ influx and increased the accumulation of hydrogen peroxide and salicylic
      acid (SA) in the A. thaliana cells. A gene with a toll interleukin 1 receptor
      nucleotide binding site-leucine-rich repeat domain (LRR) was obtained by RNA
      sequencing in combination with the screening of the gene-deletion mutants of A.
      thaliana. The LRR gene was deleted, and the inductive response of A. thaliana to
      PSP was significantly attenuated after mutation. After the heterologous
      overexpression of the LRR gene in N. benthamiana, the SA content and PR1 gene
      expression in N. benthamiana were significantly increased. Through analyses of
      the LRR gene expression and the ability of A. thaliana to resist Cucumber mosaic
      virus following the treatments of PSP and PSP + ethyleneglycol-bis (beta
      aminoethylether)-N,N'-tetraacetic acid, it was shown that PSP enhanced the virus
      resistance of A. thaliana by inducing Ca2+ influx and subsequently improving
      expression of the LRR gene, which further increased the SA content.

PMID- 29199890
TI  - Application of magnetic resonance spectroscopy in geriatric mood disorders.
AB  - The prevalence of mood disorders in the rapidly-growing older adult population
      merits attention due to the likelihood of increased medical comorbidities, risk
      of hospitalization or institutionalization, and strains placed on caregivers and
      healthcare providers. Magnetic resonance spectroscopy (MRS) quantifies
      biochemical compounds in vivo, and has been used specifically for analyses of
      neural metabolism and bioenergetics in older adults with mood disorders, usually
      via proton or phosphorous spectroscopy. While yet to be clinically implemented,
      data gathered from research subjects may help indicate potential biomarkers of
      disease state or trait or putative drug targets. Three prevailing hypotheses for
      these mood disorders are used as a framework for the present review, and the
      current biochemical findings within each are discussed with respect to particular
      metabolites and brain regions. This review covers studies of MRS in geriatric
      mood disorders and reveals persisting gaps in research knowledge, especially with
      regard to older age bipolar disorder. Further MRS work, using higher field
      strengths and larger sample sizes, is warranted in order to better understand the
      neurobiology of these prevalent late-life disorders.

PMID- 29199891
TI  - Immune response of bovine sourced cross-linked collagen sponge for hemostasis.
AB  - A comprehensive immunogenicity scheme is proposed to examine immune response of
      bovine sourced hemostasis collagen sponge to establish foundation for further
      researches and decrease the incidence of adverse reaction in clinical trials.
      Compared with negative control group without any implant, spleen and lymph nodes
      morphology show no apparent swelling in mice with different doses of collagen
      sponge implants. Immune cells population, especially lymph nodes cells
      population, is practically coincident with organs. However, splenic cells display
      slight proliferation in early phase following collagen sponge implantation.
      Splenic cells apoptosis also demonstrates no significant difference among all
      groups. T lymphocytes subsets, CD4/CD8 cells ratio, in spleen and lymph nodes are
      practically normal. Splenic cells Ki67 + proportions do not exhibit significant
      difference between collagen sponge groups and negative control group. Humoral
      response is determined by detection of IgG and IgM concentration in serum, not
      exhibiting remarkable increase with collagen sponge implantation, compared to the
      drastic increase in positive control group with bovine tendon implantation. Local
      analysis around implants by hematoxylin-eosin staining discovers slight cell
      infiltration around collagen sponge. Tumour necrosis factor-alpha immunostaining
      indicates slight inflammation in early phase following collagen sponge
      implantation, but interferon-gamma immunostaining is negligible even in positive
      control group. Collagen sponge, especially in high dose, may have evoked benign
      immune response in BALB/c mice, but this response is transient. The present
      evaluation scheme for immune response is integrated and comprehensive, suitable
      for various biomaterials.

PMID- 29199892
TI  - Localized delivery of chemokine for in vitro manipulation of hepatocellular
      carcinoma cell behaviors during the epithelial-mesenchymal transition.
AB  - Hepatocellular carcinoma develops within an altered mechanical and biochemical
      environment. The chemokine C-X-C motif chemokine ligand 12 plays an important
      role in tumor cell metastasis during the process of the epithelial-mesenchymal
      transition. Here, we successfully engineered a biomimetic matrix made up of
      polyelectrolyte films with appropriate stiffness, which could present C-X-C motif
      chemokine ligand 12 in an immobilized status in a spatially controlled manner.
      The adsorbed amounts of C-X-C motif chemokine ligand 12 could be precisely
      adjusted over a large range from 27 ng/cm2 to 2.6 ug/cm2. Immobilized C-X-C motif
      chemokine ligand 12 induced an obvious increase in hepatocellular carcinoma cell
      adhesion, spreading, and migration in a dose-dependent manner. The phenomenon was
      associated with proportion changes of three phenotypes of cell morphology (round,
      polygonal, and elongated) and higher concentrations of immobilized C-X-C motif
      chemokine ligand 12 led to the rising number of elongated cells along with up
      regulation of the mesenchymal markers, as a critical step in epithelial
      mesenchymal transition. CD44 and integrin alphavbeta3 revealed the spatial
      coincidence in three cell phenotypes. Immobilized C-X-C motif chemokine ligand 12
      induced ERK phosphorylation also exhibited dose-dependent manner. Our results
      highlight that an engineered matrix to locally deliver chemokine exhibits the
      potential to manipulate important cellular responses (including adhesion,
      spreading, migration, morphology, distribution of surface receptors, and
      signaling pathways) in the epithelial-mesenchymal transition process during
      hepatocellular carcinoma development.

PMID- 29199893
TI  - Nanoparticle/siRNA-based therapy strategies in glioma: which nanoparticles, which
      siRNAs?
AB  - Nanomedicines allow for the delivery of small interfering RNAs (siRNAs) that are
      otherwise barely suitable as therapeutics for inducing RNA interference (RNAi).
      In preclinical studies on siRNA-based glioma treatment in vivo, various groups of
      nanoparticle systems, routes of administration and target genes have been
      explored. Targeted delivery by functionalization of nanoparticles with a ligand
      for crossing the blood-brain barrier and/or for enhanced target cell transfection
      has been described as well. Focusing on nanoparticle developments in the last
      approximately 10 years, this review article gives a comprehensive overview of
      nanoparticle systems for siRNA delivery into glioma and of preclinical in vivo
      studies. Furthermore, it discusses various target genes and highlights promising
      strategies with regard to target gene selection and combination therapies.

PMID- 29199894
TI  - Local and systemic effects of a silver nitrate coated indwelling pleural catheter
      in an animal model of pleurodesis.
AB  - : Purpose/Aim of the study: This study assessed the safety and potential toxicity
      of a silver nitrate coated indwelling pleural catheter (SNCIPC) designed to
      create pleurodesis in a large animal model. MATERIALS AND METHODS: Sixteen
      animals underwent insertion of either a SNCIPC or an uncoated silicone catheter.
      Half of the animals were sacrificed at day 7 and the others at day 30. Animal
      weight and assessment of well-being, pleural fluid and blood collection were
      performed at regular intervals. Pleurodesis was assessed at necropsy and
      histopathological examination of organs performed. RESULTS: No mortality or
      significant clinical findings were observed throughout the experiment. SNCIPC
      treated animals had increased pleural fluid drainage overall (p < 0.001) and
      specifically on days 1-4. No differences in hemoglobin, white blood cell count or
      neutrophil counts were detected between groups. No treatment related histological
      findings were observed in any of the evaluated tissues outside of the treated
      area. Serum silver levels in SNCIPC catheter treated animals peaked on Day 4
      (0.185 MUg/mL, 30 day group) then gradually decreased for the remainder of the
      study period. The highest tissue silver concentrations were noted in the SNCIPC
      groups in tissues close to the treatment site in addition to the liver (59.8ug/g
      +/- 8.6 and 73.3ug/g +/- 25). Pleurodesis scores were significantly higher in
      SNCIPC treated animals for both the 7 day (median 6.5 vs. 1.0, p = 0.029) and 30
      day cohorts (median 7.0 vs. 1.5, p = 0.029). CONCLUSIONS: SNCIPC are well
      tolerated and not associated with any significant signs of toxicity. Silver
      levels were elevated in local tissues, serum and liver but without evidence of
      pathological impact. Effective pleurodesis was present by day 7 and more
      established by day 30. Clinical studies to investigate the safety and efficacy of
      this device in patients with malignant pleural effusions appear warranted.

PMID- 29199895
TI  - Radiological evaluation of scapholunate intercarpal ligamentoplasty for chronic
      scapholunate dissociation in cadavers.
AB  - We performed a cadaveric study to evaluate radiological performance of a
      technique for scapholunate intercarpal ligamentoplasty designed for treating
      reducible scapholunate dissociation. We created scapholunate instability in 12
      fresh adult cadaveric forearms by sectioning the dorsal scapholunate interosseous
      ligament and the dorsal intercarpal ligament. All wrists showed scapholunate
      diastasis, dorsal intercalated segmental instability and posterior scaphoid
      subluxation. We performed scapholunate intercarpal ligamentoplasty in six wrists
      and Garcia-Elias three-ligament tenodesis in another six. Wrists were examined
      radiographically both after ligament sectioning and after ligamentoplasty to
      compare static and dynamic scapholunate gaps and scapholunate and capitolunate
      angles. Improvement was statistically significant in all measurements, reflecting
      a return to normal values. Posterior scaphoid subluxation was also corrected.
      There was no significant difference between the two treatment groups. Our
      findings suggest that ligamentoplasty can restore scapholunate joint stability
      and normal carpal anatomy.

PMID- 29199896
TI  - Sexual Norms for Lesbian and Bisexual Women in a Culture Where Lesbianism Is Not
      Acceptable Enough: The Japanese Survey About Sexual Behaviors, STIs Preventive
      Behaviors, and the Value of Sexual Relations.
AB  - This study aimed to identify key factors preventing STIs among women who have sex
      with women in Japan. This description is based on survey and open-ended responses
      from participants. The questionnaire contained participants' background, sexual
      behavior, STI prevention behavior, experience and knowledge of STIs, and the
      value of sex with women. 104 responded, and 92 (88.5 %) reported having sexual
      experience with women. A variety of sexual behaviors were reported. Regarding
      STIs, 14.4% of participants had an STI in past. Almost half of the participants
      cited measures to prevent STIs included hygienic activities. Participants
      believed that sexual relations accompany partnership with females.

PMID- 29199897
TI  - Upper and lower limb loading during weight-bearing activity in children: reaction
      forces and influence of body weight.
AB  - Weight bearing (WB) activity is important for healthy skeletal development. The
      magnitude of loading during WB activities, especially upper limb impacts, has yet
      to be quantified in children. This study quantifies ground reaction forces (GRF)
      experienced by children performing WB activities and examines the contribution of
      body weight (BW) to GRF. Fifty children, aged 8-12 were recruited (34 males). GRF
      were measured using force plates during 20 upper and lower limb activities (such
      as landing on the feet and hands). Sex differences in GRF and associations
      between peak force and BW were examined using independent sample t-tests and
      linear regressions (p < 0.05), respectively. Lower limb GRF varied from 2-6x BW
      with no significant sex differences. GRF during upper limb activities varied from
      1/3-1.7x BW with males experiencing significantly greater GRF for 25% of
      activities. BW was significantly associated with peak force in almost all
      activities; however, GRF variation explained by BW was wide-ranging across
      activities and not dependent on limb or activity type (static vs dynamic).
      Therefore, factors other than BW, such as technique, may be important in
      determining forces experienced by children performing WB activity and should be
      considered when choosing activities for WB activity interventions.

PMID- 29199898
TI  - Conditional Effects of Gain-Loss-Framed Narratives among Current Smokers at
      Different Stages of Change.
AB  - This study examines how current smokers respond differently to gain-loss-framed
      antismoking narratives depending on their stages of change to quit smoking. An
      experiment (N = 461) was conducted with a 2 (narrative perspective: first person
      vs. third person) * 2 (framing: gain vs. loss) factorial design having smoker's
      stage of change (precontemplation vs. contemplation/preparation) as a moderator.
      We observed differential framing effects depending on smoker's current stages of
      change only when they were exposed to first-person narratives. For
      precontemplators, a loss-framed (vs. a gain-framed) first-person narrative
      induced greater quit intentions and stage progression. Conversely, among
      contemplators and preparers, a gain-framed (vs. a loss-framed) first-person
      narrative led to greater quit intentions and stage progression. These interactive
      patterns were partly mediated by self-referencing and perceived similarity. This
      study proposes an alternative mechanism to explain the conditional framing effect
      by stages of change and highlights the importance of tailoring messages to
      smoker's psychosocial characteristics and needs.

PMID- 29199899
TI  - Alcohol and Drug Use, Pain and Psychiatric Symptoms among Adults Seeking
      Outpatient Psychiatric Treatment: Latent Class Patterns and Relationship to
      Health Status.
AB  - BACKGROUND: Substance use, psychiatric problems, and pain frequently co-occur,
      yet clinical profiles of treatment-seeking patients are poorly understood. To
      inform service and treatment planning, substance use and symptom patterns were
      examined in an outpatient psychiatry clinic, along with the relationship of these
      patterns to demographic characteristics and physical health. METHODS: Patients (N
      = 405; age M = 38; 69% White; 60% female) presenting for intake in a psychiatry
      outpatient clinic completed a computerized assessment of psychiatric problems,
      drinking, and drug use. Substance use and psychiatric symptom patterns among the
      sample were identified using latent class analysis. RESULTS: A 4-class model fit
      the data best: Class (1) Moderate symptoms/wide-range users (22.0%) had moderate
      depression and panic; tobacco, cocaine, hallucinogen, and ecstasy use; and high
      cannabis use. Class (2) Moderate depression/panic (37.8%) had moderate depression
      and panic. Class (3) Depression/anxiety, tobacco, and cannabis users (28.0%) had
      high depression, obsessions, and panic, and moderate pain severity, social
      phobia, compulsions, trauma, tobacco, and cannabis use. Class (4) Severe/wide
      range symptoms/users (12.0%) had high panic, depression, social phobia,
      obsessions, drug use, and moderate pain. Gender, ethnicity, and health status
      varied by class. CONCLUSIONS: Findings highlight the preponderance of substance
      use (particularly cannabis) and its relationship to psychiatric symptom severity,
      pain, and health status among those presenting for mental health treatment.

PMID- 29199901
TI  - An Evaluation of Practitioner's Experience of Service Users Seeking Community
      Detoxification from Benzodiazepines.
AB  - A recent report in Ireland identified that two-thirds of poisoning deaths
      involved poly drug use with an average of four different drugs involved. Of
      these, benzodiazepines were the most common drug group involved. Concern has been
      expressed regarding high levels of benzodiazepine prescriptions globally.
      Community-based detoxification programs are required, but detoxification is
      complex with associated high risks, such as overdose. This study utilized a
      survey to gather the experiences of a range of drug workers in addiction settings
      in the southern region of Ireland who are tasked with the management of
      supporting service users who wish to detoxify from benzodiazepines. The purpose
      of this study is to identify the issues highlighted in the data and consequently
      inform policy development, service delivery, future training, and pathways to
      support service users (SUs). Findings indicate that, while practitioners had high
      levels of confidence in managing community-based detoxes, levels of knowledge of
      schedules, contraindications, access to support, and appropriate referral
      pathways were limited. Barriers to supporting detoxes emerged, emphasizing the
      importance of multidisciplinary and interagency care planning. Changing trends in
      drug use led participants to indicate a need for pharmacology training and
      development of specific local protocols.

PMID- 29199900
TI  - A prescribed walking regimen plus arginine supplementation improves function and
      quality of life for patients with pulmonary arterial hypertension: a pilot study.
AB  - Current evidence suggests that exercise training is beneficial in pulmonary
      arterial hypertension (PAH). Unfortunately, the standard supervised, hospital
      based programs limit patient accessibility to this important intervention. Our
      proof-of-concept study aimed to provide insight into the usefulness of a
      prescribed walking regimen along with arginine supplementation to improve
      outcomes for patients with PAH. Twelve PAH patients (all women) in New York Heart
      Association (NYHA) functional class (FC) II (n = 7) or III (n = 5) and in stable
      condition for >= 3 months were enrolled. Patients performed home- and fitness
      center- based walking at 65-75% heart rate (HR) reserve for 45 min, six
      sessions/week for 12 weeks. Concomitant L-arginine supplementation (6000 mg/day)
      was provided to maximize beneficial endothelial training adaptations.
      Cardiopulmonary exercise testing, 6-min walk testing (6MWT), echocardiography,
      laboratory studies, and quality of life (QoL) survey (SF-36) were performed at
      baseline and 12 weeks. Eleven patients completed the study (72 session adherence
      rate = 96 +/- 3%). Objective improvement was demonstrated by the 6MWT distance
      (increased by 40 +/- 13 m, P = 0.01), VO2max (increased by 2 +/- 0.7 mL/kg/min, P
      = 0.02), time-to-VO2max (increased by 2.5 +/- 0.6 min, P = 0.001), VO2 at
      anaerobic threshold (increased by 1.3 +/- 0.5 mL/kg/min, P = 0.04), HR recovery
      (reduced by 68 +/- 23% in slope, P = 0.01), and SF-36 subscales of Physical
      Functioning and Energy/Fatigue (increased by 70 +/- 34% and 74 +/- 34%,
      respectively, P < 0.05). No adverse events occurred, and right ventricular
      function and brain natriuretic peptide levels remained stable, suggesting safety
      of the intervention. This proof-of-concept study indicates that a simple walking
      regimen with arginine supplementation is a safe and efficacious intervention for
      clinically stable PAH patients, with gains in objective function and QoL
      measures. Further investigation in a randomized controlled trial is warranted.

PMID- 29199902
TI  - Examining associations among sensitivity to punishment and reward, shame, and
      eating pathology through tests of mediation.
AB  - This study investigated associations between sensitivity to punishment and
      reward, shame, and eating pathology by testing alternative mediation models in
      which shame mediated associations between temperament and eating pathology or
      eating pathology mediated associations between temperament and shame.
      Participants were 96 female undergraduate students who completed questionnaires.
      Results indicated shame fully mediated the relationship between sensitivity to
      punishment and eating pathology. Further, eating pathology did not mediate the
      association between sensitivity to punishment and shame. In contrast, for
      sensitivity to reward, shame fully mediated the relationship between sensitivity
      to reward and eating pathology, and eating pathology fully mediated the
      relationship between sensitivity to reward and shame. If associations are
      supported by longitudinal research, results suggest that it may be valuable to
      develop prevention approaches targeting shame to reduce risk for the development
      of eating pathology for those who are high in sensitivity to punishment. For
      those higher in sensitivity to reward, interventions targeting shame may reduce
      risk for eating pathology and those targeting eating pathology may reduce shame.

PMID- 29199904
TI  - The Association of Oncology Social Work's Project to Assure Quality Cancer Care
      (APAQCC).
AB  - In 2014, the Association for Oncology Social Work (AOSW) established A Project to
      Assure Quality Cancer Care (APAQCC), a group of oncology social workers
      representing sixty-five Commission on Cancer (CoC)-accredited cancer programs
      across the US (including two in Canada). Its aims were (1) to examine the
      capacity of cancer programs to provide quality psychosocial support services, and
      (2) to evaluate the implementation of distress screening. The purpose of this
      paper is to describe how this collaborative research program was created and
      implemented under the auspices of AOSW, and to report on its impact on the
      oncology social workers who participated.

PMID- 29199903
TI  - More than a biomarker: the systemic consequences of heparan sulfate fragments
      released during endothelial surface layer degradation (2017 Grover Conference
      Series).
AB  - Advances in tissue fixation and imaging techniques have yielded increasing
      appreciation for the glycosaminoglycan-rich endothelial glycocalyx and its in
      vivo manifestation, the endothelial surface layer (ESL). Pathological loss of the
      ESL during critical illness promotes local endothelial dysfunction and,
      consequently, organ injury. Glycosaminoglycan fragments, such as heparan sulfate,
      are released into the plasma of animals and humans after ESL degradation and have
      thus served as a biomarker of endothelial injury. The development of state-of-the
      art glycomic techniques, however, has revealed that these circulating heparan
      sulfate fragments are capable of influencing growth factor and other signaling
      pathways distant to the site of ESL injury. This review summarizes the current
      state of knowledge concerning the local (i.e. endothelial injury) and systemic
      (i.e. para- or endocrine) consequences of ESL degradation and identifies
      opportunities for future, novel investigations.

PMID- 29199905
TI  - Potentially inappropriate medication in primary care at the end of life: a mixed
      method study.
AB  - CONTEXT: Polypharmacy results in adverse drug interactions, high pill burden, and
      medication costs. Stopping or diminishing potentially inappropriate medication
      (PIM), is complex . Data on the use of PIM in a primary care context are scarce
      and deprescribing barriers for general practitioners (GP) are underexplored.
      OBJECTIVE: Describing the use of PIM in primary care at the end of life, and
      exploring the barriers for GPs to deprescribe. METHODS: Retrospective chart
      review of 210 consecutive patients referred to a palliative home care service and
      semi-structured interviews with 11 GPs. Percentages were calculated on medication
      use, linear regression was done to evaluate the effect of diagnosis on PIM use.
      Thematic analysis was used to analyze the interviews. RESULTS: In total 83 % of
      patients took at least one PIM. The proportion that continued taking PIMs at the
      time of referral, one week prior to death and at the day of dying: varies between
      6% and 45% according to drug category. Linear regression showed a statistical
      significant (p < 0.001) higher number of PIM use with non-cancer patients (mean
      3,1-SD 1,5) than with cancer patients (mean 1,6-SD 1,6). Participants reported
      being aware of the PIM use, making efforts to deprescribe. Main issues GPs are
      taking into account are medical, communicative, and collaborative in nature.
      CONCLUSION: This study confirms the high level of PIM use in primary care at the
      end of life. The views of GPs inspire support strategies for deprescribing
      focusing on shared decision-making with patients and on interprofessional
      collaboration.

PMID- 29199906
TI  - Racial/Ethnic Differences in Prevalence and Correlates of Blunt Smoking among
      Adolescents.
AB  - Blunt use is pervasive among adolescents. The study uses cross-sectional data
      from the 2014 National Survey on Drug Use and Health to examine sociodemographic,
      health, and other substance use correlates of current and lifetime blunt use
      among 12,036 African American, White, and Hispanic/Latino adolescents. Findings
      revealed that 5.3% of African American, 4.3% of Hispanic/Latino, and 3.8% of
      White adolescents reported past-30-day blunt use. Age and substance use other
      than marijuana were consistent correlates of current and lifetime blunt use
      across all racial/ethnic groups. However, other illicit drug use and alcohol use
      were differentially associated with lifetime and past-30-day blunt use by
      race/ethnicity. Gender, family income, lifetime depression, and overall health
      status were not associated with lifetime or past-30-day blunt use. The link
      between other substance use and blunt use varies by race/ethnicity among
      adolescents. Future blunt use prevention and treatment interventions should
      consider racial/ethnic differences in the association between other substance use
      and blunt use among African American, White, and Hispanic/Latino adolescents.

PMID- 29199907
TI  - Gaydar, Marriage, and Rip-Roaring Homosexuals: Discourses About Homosexuality in
      Dear Abby and Ann Landers Advice Columns, 1967-1982.
AB  - Over the past 70 years, the history of acceptance of the lesbian, gay and
      bisexual (LGB) community within the United States has seen much change and
      fluctuation. One of the places that this dialogue has been preserved is through
      the syndicated advice columns of Dear Abby and Ann Landers, in which individuals
      in the United States were writing in for advice to deal with their anxiety over a
      newly emerging and highly visible new community of individuals once considered to
      be mentally ill and dangerous. Using discourse analysis, this article traces the
      evolution of public and scientific opinions about the LGBT community during the
      years leading up to the Stonewall riots all the way to right before the AIDs
      epidemic. This analysis sheds light on several moral panics that emerged
      regarding this newly visible population, especially in regard to disturbances
      within the domestic sphere and a stigmatization of bisexuality.

PMID- 29199908
TI  - "We are Two of the Lucky Ones": Experiences with Marriage and Wellbeing for Same
      Sex Couples.
AB  - Happy marriages provide protective health benefits, and social support is a key
      factor in this association. However, previous research indicates one of the
      greatest differences between same- and different-sex couples is less social
      support for same-sex couples. Our goal was to examine the extent to which formal
      markers of couple status (e.g., marriage) impact wellbeing among same-sex married
      partners. Using a mixed-methods approach, data were collected from 218 primarily
      White gay and lesbian individuals in the Midwest. Quantitative analysis revealed
      individuals in a prior formal union with a different-sex partner reported the
      lowest levels of sexuality specific social support and acceptance. Qualitative
      analysis revealed four primary impacts of marriage on support from family,
      friends, and co-workers: no change, increased support, decreased support, and a
      synthesis of mixed support. Three mechanisms prompting change in the family were
      identified and are presented.

PMID- 29199909
TI  - Research Priorities for Healthcare Chaplaincy: Views of U.S. Chaplains.
AB  - Chaplains in the United States and around the world appear to support an evidence
      based practice approach to chaplaincy. While there continues to be strong growth
      in spiritual care research, several spiritual care researchers have stressed the
      need for a research agenda for chaplaincy. This study investigated the research
      priorities of chaplains who completed a survey distributed at four chaplaincy
      conferences in 2016. A total of 193 chaplains responded, resulting in 499
      comments. When compared to the findings of existing literature regarding research
      priorities for chaplaincy, chaplain's views of research priorities appear to be
      very consistent with views of chaplaincy leaders. Both prioritize research on
      outcomes of spiritual care, the development and testing of the effectiveness of
      interventions, the development and evaluation of assessment and screening tools
      and research about key subgroups of patients. The chaplains in the survey however
      added to the agenda research regarding competencies, education, and certification
      and research regarding the chaplain and the team.

PMID- 29199910
TI  - Impact of four times daily dosing of oral treprostinil on tolerability and daily
      dose achieved in pulmonary hypertension.
AB  - Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of
      patients with pulmonary arterial hypertension (PAH). Dosing is approved for two
      or three times daily (t.i.d.); however, adverse effects, including
      gastrointestinal-related symptoms, may limit the ability to reach optimal doses.
      We report our experience with a four times daily (q.i.d.) regimen of oral TRE for
      goal-directed therapy of PAH. We describe three patients that were transitioned
      from infusion or inhaled TRE to oral TRE with initial t.i.d. dosing over a four
      day hospital stay. All patients were subsequently further dose-adjusted in the
      outpatient setting; however, adverse effects limited additional up-titration
      despite persistent dyspnea. In a carefully monitored outpatient setting, patients
      were switched from t.i.d. to q.i.d. dosing of oral TRE. All three patients were
      successfully dosed q.i.d., having achieved a higher total daily dose compared
      with a t.i.d. dose regimen. Furthermore, patients were able to maintain
      functional class II symptoms with mitigation of adverse effects using the q.i.d.
      dose regimen.

PMID- 29199911
TI  - An unexpected cause of liver cirrhosis and cardiomyopathy in a young man.
AB  - Introduction Juvenile hemochromatosis is a rare but severe form of hereditary
      hemochromatosis that typically presents early in life and can be fatal if left
      untreated. Case presentation We present the case of a 30-year-old man with a
      clear symptomatology of juvenile hemochromatosis, but in whom the diagnosis was
      initially mistaken for alcoholic liver disease because of known excessive use of
      alcohol, with the consequence that an adequate treatment was postponed.
      Discussion In this report, we discuss the diagnosis and treatment of juvenile
      hemochromatosis, focusing on the interaction between hemochromatosis and alcohol
      induced liver disease and how to differentiate both. We conclude that every young
      patient with suspected alcoholic liver disease and signs of iron overload should
      have a testing to rule out other iron overloading pathology, since early
      recognition and treatment with phlebotomy may prevent organ damage and improve
      life expectancy.

PMID- 29199912
TI  - The Effects of School-Based Discrimination on Adolescents of Color Sexual Health
      Outcomes: A Social Determinants Approach.
AB  - Social inequalities are at the heart of disparities in sexual health outcomes
      among African American and Latino/a adolescents living in the United States.
      Schools are typically the largest and primary context in youth development.
      School characteristics such as peer and teacher discrimination and school
      performance were examined to determine whether such characteristics predict
      sexual behavior in adolescents of color. This study utilized a representative
      sample of high school age students to assess sexual risk behavior. Findings
      indicate that there was a clear disparity in sexually transmitted infection
      diagnoses. School characteristics such as teacher discrimination and Grade Point
      Average were significant predictors to sexual risky behaviors among adolescents
      of color. The study adds to the literature in examining contextual factors that
      are associated with adolescent sexual risk behavior, and findings provide
      implications for future prevention work.

PMID- 29199913
TI  - Elimination of mother-to-child transmission of syphilis: Is it a reality in
      Nigeria by 2020?
AB  - BACKGROUND: Congenital syphilis is a global health problem, yet it has received
      little attention in recent years. Despite cost-effective syphilis screening and
      treatment, it continues to contribute hugely to perinatal morbidity and mortality
      worldwide. AIMS: To determine the prevalence and treatment coverage trend for
      syphilis among pregnant women in the national prevention of mother-to-child
      transmission programme in Nigeria and to evaluate progress towards the
      elimination of congenital syphilis in the country. METHODS: A retrospective
      analysis of validated national health sector performance data on pregnant women
      attending antenatal care at prevention of mother-to-child transmission clinics
      from 2013 to 2016 in Nigeria. RESULTS: The proportion of new antenatal care
      attendees who annually received serological testing for syphilis increased from
      12.2% in 2013 to 16.3% in 2016 (p-trend<0.0001). Although the prevalence of
      maternal syphilis decreased from 3.2% in 2013 to 1.4% in 2016 (p-trend<0.0001),
      the syphilis treatment coverage during pregnancy has decreased from 71.3% in 2013
      to 54.9% in 2016 (p-trend<0.0001). CONCLUSIONS: Maternal syphilis screening and
      treatment in Nigeria are inadequate to meet the elimination aspirations. A rapid
      scale-up of antenatal care syphilis screening and treatment are crucial to
      averting an epidemic in Nigeria by 2020.

PMID- 29199914
TI  - Rethinking the relationship between socioeconomic status and health: Challenging
      how socioeconomic status is currently used in health inequality research.
AB  - AIMS: The Scandinavian Journal of Public Health recently reiterated the
      importance of addressing social justice and health inequalities in its new
      editorial policy announcement. One of the related challenges highlighted in that
      issue was the limited use of sociological theories able to inform the complexity
      linking the resources and mechanisms captured by the concept of socioeconomic
      status. This debate article argues that part of the problem lies in the often
      unchallenged reliance on a generic conceptualization and operationalization of
      socioeconomic status. These practices hinder researchers' capacity to examine in
      finer detail how resources and circumstances promote the unequal distribution of
      health through distinct yet intertwined pathways. As a potential way forward,
      this commentary explores how research practices can be challenged through
      concrete publication policies and guidelines. To this end, we propose a set of
      recommendations as a tool to strengthen the study of socioeconomic status and,
      ultimately, the quality of health inequality research. CONCLUSIONS: Authors,
      reviewers, and editors can become champions of change toward the implementation
      of sociological theory by holding higher standards regarding the
      conceptualization, operationalization, analysis, and interpretation of results in
      health inequality research.

PMID- 29199915
TI  - Extent and quality of drug use in community-dwelling people aged >=75 years: A
      Swedish nationwide register-based study.
AB  - AIMS: It is important for district nurses and other health professionals in
      primary care to gain more insight into the patterns and quality of drug use in
      community-dwelling older people, particularly in 75-year-olds, who have been the
      target of preventive home visits. This study aimed to examine the extent and
      quality of drug use in community-dwelling older people and to compare drug use in
      75-year-olds with that of older age groups. METHODS: Data from 2013 on people
      aged >=75 years were obtained from the Swedish Prescribed Drug Register. Those
      living in the community (671,940/739,734 people aged >=75 years) were included in
      the study. Quality of drug use was assessed by using a selection of indicators
      issued by the Swedish National Board of Health and Welfare. RESULTS: The
      prevalence of polypharmacy and of many drug groups increased with age, as did
      several indicators of inappropriate drug use. However some drug groups, as well
      as inappropriate drugs, were prevalent in 75-year-olds and declined with age, for
      example diabetes drugs, drugs with major anticholinergic effects and nonsteroidal
      anti-inflammatory drugs. CONCLUSIONS: The substantial use of some drugs as early
      as 75 years of age confirms the value of including drug use as a topic in
      preventive home visits to 75-year-olds. The finding that polypharmacy and many
      measures of inappropriate drug use increased with age in community-dwelling older
      people also underscores the importance of district nurses' role in continuing to
      promote safe medication management at higher ages.

PMID- 29199916
TI  - Independent medical evaluation for sick-listed workers in Norway: A focus group
      study of the experience of IME doctors.
AB  - BACKGROUND: Norwegian politicians have proposed the use of an independent medical
      evaluation (IME) as a possible solution for reducing long-term sick leave. The
      use of an IME implies that a new doctor interferes in the relationship between
      sick-listed workers and their general practitioner (GP). The aim of the current
      study was to explore experiences of IME doctors from an ongoing randomized
      controlled trial (the NIME trial evaluating the effect of IME in Norway).
      METHODS: Two focus group interviews were conducted with eight of the nine IME
      doctors employed in the NIME trial. The discussions were audio-taped and
      transcribed. Systematic text condensation was used for analysis. RESULTS: The
      participants reported that the IME provides important second opinions, which they
      felt empowered the sick-listed workers and provided new insights into their
      condition. Beneficial IME working conditions and enhanced insight into different
      sick leave measures were crucial to this perceived usefulness. Some of the
      participants expressed disappointment with GPs acting as passive conductors and
      struggled to provide feedback politely. Some adjustments were proposed as
      necessary for the IME to be implemented nationwide. CONCLUSIONS: The participants
      seemed to have gained a different stakeholder identity by sometimes seeing GPs,
      their peers, as obstacles to return to work and welcomed the use of IME on a
      regular basis.

PMID- 29199917
TI  - Has life satisfaction in Norway increased over a 20-year period? Exploring age
      and gender differences in a prospective longitudinal study, HUNT.
AB  - AIM: The aim of the present study was to investigate the change in overall life
      satisfaction for different age groups and between genders over a 20-year period.
      METHODS: Data from 1984 to 2008 were extracted from a large prospective
      longitudinal health study of Nord-Trondelag (HUNT), Norway. The study included
      more than 176,000 participants ranging from 20 to 70+ years of age. Data were
      analysed using logistic regression and adjusted for gender. RESULTS: The analyses
      revealed an increase in life satisfaction for all age groups from 1984-1986 (HUNT
      1) to 1995-1997 (HUNT 2), with the highest levels being reached at 2006-2008
      (HUNT 3). For all age groups, the data showed an increase of about 20% for the
      period from 1984-1986 (HUNT 1) to 1995-1997 (HUNT 2). From 1995-1997 (HUNT 2) to
      2006-2008 (HUNT 3), the increase in overall life satisfaction was 16% for the
      younger age groups, and about 32% for the older age groups (40-69 and 70+ years).
      Women's scores for overall life satisfaction were higher for nearly all age
      groups when compared to men using HUNT 3 as a reference. CONCLUSIONS: These
      findings suggest an increase in life satisfaction for all age groups from 1984 to
      2008, especially for the older age group (40-69 and 70+ years). The data indicate
      that women score higher on life satisfaction for most age groups as compared to
      men.

PMID- 29199919
TI  - Editorial: Molecular Scenarios Behind Infectious Diseases.

PMID- 29199918
TI  - Editorial: Improving Neuropharmacology using Big Data, Machine Learning and
      Computational Algorithms.

PMID- 29199920
TI  - Consumers' understanding and expectations of a community-based recovery-oriented
      mental health rehabilitation unit: a pragmatic grounded theory analysis.
AB  - AIMS: Incorporating consumer perspectives into mental health services design is
      important in working to deliver recovery-oriented care. One of the challenges
      faced in mental health rehabilitation services is limited consumer engagement
      with the available support. Listening to consumers' expectations of mental health
      services, and what they hope to achieve, provides an opportunity to examine the
      alignment between existing services and the priorities and preferences of the
      people who use them. We explored consumer understandings and expectations of
      three recovery-oriented community-based residential mental-health rehabilitation
      units using semi-structured interviews; two of these units were trialling a
      staffing model integrating peer support with clinical care. METHODS: Twenty-four
      consumers completed semi-structured interviews with an independent interviewer
      during the first 6 weeks of their stay at the rehabilitation unit. Most
      participants had a primary diagnosis of schizophrenia or a related psychotic
      disorder (87%). A pragmatic approach to grounded theory guided the analysis,
      facilitating identification of content and themes, and the development of an
      overarching conceptual map. RESULTS: The rehabilitation units were considered to
      provide a transformational space and a transitional place. The most common reason
      given for engagement was housing insecurity or homelessness rather than the
      opportunity for rehabilitation engagement. Differences in expectations did not
      emerge between consumers entering the clinical and integrated staffing model
      sites. CONCLUSIONS: Consumers understand the function of the rehabilitation
      service they are entering. However, receiving rehabilitation support may not be
      the key driver of their attendance. This finding has implications for promoting
      consumer engagement with rehabilitation services. The absence of differences
      between the integrated and clinical staffing models may reflect the novelty of
      the rehabilitation context. The study highlights the need for staff to find
      better ways to increase consumer awareness of the potential relevance of evidence
      based rehabilitation support to facilitating their recovery.

PMID- 29199921
TI  - Developing a community HCV service: project ITTREAT (integrated community-based
      test - stage - TREAT) service for people who inject drugs.
AB  - : Background and aims Majority of the individuals with hepatitis C virus (HCV)
      infection in England are people who inject drugs, a vulnerable and
      disenfranchised cohort with poor engagement with secondary care. Our aim is to
      describe our experiences in setting up a successful nurse led HCV service at a
      substance misuse service (SMS). METHODS: We justify the need for a community HCV
      service and review the different community based models. Our experiences in
      engaging with stakeholders, obtaining funding, service set up, challenges faced
      and key recommendations are discussed. Finally, a summary of interim clinical
      outcomes is presented. RESULTS: A successful community based "one-stop" nurse led
      HCV service was set up in Dec 2013 at a large SMS. It provides all aspects of
      care (blood borne virus screening, non-invasive assessment of hepatic fibrosis,
      Hepatology input, HCV treatment, peer mentor, social and psychiatrist support,
      and opiod substitution) at one site. Interim clinical data indicate high service
      uptake with HCV treatment outcomes comparable to secondary care. CONCLUSIONS: The
      advent of direct acting antivirals provides a unique opportunity for HCV
      elimination in England by 2030. Our "one-stop" integrated and multidisciplinary
      community HCV model suggests that HCV care can be successfully delivered outside
      of a hospital setting and warrants national adoption.

PMID- 29199922
TI  - Evaluating population salt reduction programmes worldwide: the risk of cutting
      corners!

PMID- 29199923
TI  - Micronutrient status in middle childhood and age at menarche: results from the
      Bogota School Children Cohort.
AB  - Childhood intake of animal foods is associated with age at first menstrual period
      (menarche). It is unknown whether the micronutrients present in these foods could
      explain this association. Our objective was to investigate the associations of
      micronutrient status biomarkers in middle childhood with age at menarche. We
      quantified circulating Hb, ferritin, mean corpuscular volume, Zn, vitamin B12,
      erythrocyte folate and retinol in 1464 pre-menarcheal girls aged 5-12 years in
      Bogota, Colombia, and followed them for a median 5.7 years for the occurrence and
      date of menarche. We estimated median age at menarche and hazard ratios (HR) with
      95 % CI by levels of each biomarker with use of Kaplan-Meier survival
      probabilities and Cox regression, respectively. Median age at menarche was 12.4
      years. Middle childhood Hb was inversely related to age at menarche whereas
      plasma ferritin was positively associated with this outcome in a linear manner.
      HR of menarche for every 1 sd of Hb (11 g/l) and ferritin (23.2 ug/l) were 1.11
      (95 % CI 1.04, 1.18; P=0.001) and 0.94 (95 % CI 0.88, 0.99; P=0.02),
      respectively, after adjustment for baseline age, C-reactive protein
      concentration, maternal age at menarche and parity and socioeconomic status. The
      association with ferritin was stronger in girls aged 9-10 years at baseline.
      Additional adjustment for baseline height- and BMI-for-age did not change the
      results. We conclude that higher Fe status in middle childhood is related to
      later age at menarche whereas Hb concentrations are inversely associated with age
      at onset of menses.

PMID- 29199925
TI  - Exhibiting Good Health: Public Health Exhibitions in London, 1948-71.
AB  - This article examines the changing nature of public health services and their
      relationship with the public in post-war Britain by an analysis of the
      exhibitions mounted by Medical Officers of Health (MOsH) in London. Focusing on
      the period 1948-71, the article explores a time when public health practice, and
      the problems it faced, were in flux. A decline in infectious disease and an
      increase in chronic conditions linked to lifestyle required a new role for public
      health services. Exhibitions were one of several methods that MOsH used to inform
      the public about dangers to their health, but also to persuade them to change
      their behaviour. The exhibition, though, offers a unique insight into the
      relationship between public health authorities and the public, as exhibitions
      brought MOsH into direct contact with people. It is suggested that in the MOsH
      exhibitions we can find signs of a new relationship between public health
      practitioners and the public. Whilst elements of the pre-war, often moralistic
      ideology of public health services could still be detected, there is also
      evidence of a more nuanced, responsive dynamic between practitioners and the
      people. By the end of the 1960s, 'the public' was increasingly being thought of
      as a collection of 'publics', including individuals, target groups and vocal
      respondents.

PMID- 29199924
TI  - Longitudinal Associations among Posttraumatic Stress Disorder Symptoms, Traumatic
      Brain Injury, and Neurocognitive Functioning in Army Soldiers Deployed to the
      Iraq War.
AB  - OBJECTIVES: Military deployment is associated with increased risk of adverse
      emotional and cognitive outcomes. Longitudinal associations involving
      posttraumatic stress disorder (PTSD), relatively mild traumatic brain injury
      (TBI), and neurocognitive compromise are poorly understood, especially with
      regard to long-term outcomes, and rigorous research is necessary to better
      understand the corresponding relationships. The objective of this study was to
      examine short-term and long-term (>5 years) longitudinal associations among PTSD,
      neurocognitive performance, and TBI following military deployment. METHODS: In
      this prospective study, N=315 U.S. Army soldiers were assessed at military
      installations before (2003-2005) and after (2004-2006) an index deployment to the
      Iraq War, and again an average of 7.6 years later (2010-2014) as a nationally
      dispersed cohort of active duty soldiers, reservists, and veterans. Thus, the
      study design allowed for two measurement intervals over which to examine changes.
      All assessments included the PTSD Checklist, civilian version, and individually
      administered performance-based neurocognitive tests. TBI history was derived from
      clinical interview. RESULTS: Autoregressive analyses indicated that visual
      reproduction scores were inversely related to subsequent PTSD symptom severity at
      subsequent assessments. Conversely, increases in PTSD symptom severity over each
      measurement interval were associated with poorer verbal and/or visual recall at
      the end of each interval, and less efficient reaction time at post-deployment.
      TBI, primarily mild in this sample, was associated with adverse PTSD symptom
      outcomes at both post-deployment and long-term follow-up. CONCLUSIONS: These
      results suggest longitudinal relationships among PTSD symptoms, TBI, and
      neurocognitive decrements may contribute to sustained emotional and
      neurocognitive symptoms over time. (JINS, 2018, 24, 311-323).

PMID- 29199926
TI  - 'From Defensive Paranoia to ...Openness to Outside Scrutiny': Prison Medical
      Officers in England and Wales, 1979-86.
AB  - This article examines how a branch of medicine based within the criminal justice
      system responded to a society which by the 1970s and 1980s was increasingly
      critical of the prison system and medical authority. The Prison Medical Service,
      responsible for the health care of prisoners in England and Wales, was criticised
      by prison campaigners and doctors alike for being unethical, isolated, secretive,
      and beholden to the interests of the Home Office rather than those of their
      patients. While prison doctors responded defensively to criticisms in the 1970s
      and 1980s, comparing their own standards of practice favourably with those found
      in the NHS, and arguing that doctors from outside would struggle to cope in the
      prison environment, by 1985 their attitudes had changed. Giving evidence to a
      House of Commons committee, prison doctors displayed a much greater willingness
      to discuss how the prison system made their work more difficult, and expressed a
      pronounced desire to engage openly with the rest of the profession to address
      these problems. The change of attitude partly reflects a desire by the Home
      Secretary William Whitelaw to make the Prison Service more open, and an
      acceptance of a need for greater accountability in medicine generally. Most
      important, however, was a greater interest in prison health care and appreciation
      of the difficulties of prison practice among the wider medical profession,
      encouraging prison doctors to speak out. This provides a case study of how a
      professional group could engage openly with criticisms of their work under
      favourable circumstances.

PMID- 29199927
TI  - Boyish Mannerisms and Womanly Coquetry: Patients with the Diagnosis of
      Transvestitismus in the Helsinki Psychiatric Clinic in Finland, 1954-68.
AB  - This article examines the case files of patients diagnosed with Transvestitismus
      [transvestism] in the Psychiatric Clinic of the Helsinki University Central
      Hospital in the years 1954-68. These individuals did not only want to cross
      dress, but also had a strong feeling of being of a different sex from their
      assigned one. The scientific concept of transsexuality had begun to take form,
      and this knowledge reached Finland in phases. The case files of the transvestism
      patients show that they were highly aware of their condition and were very
      capable of describing it, even if they had no medical name for it. Psychiatrists
      were willing to engage in dialogue with the patients, and did not treat them as
      passive objects of study. Although some patients felt that they had been helped,
      many left the institution as frustrated, angered or desperate as before. They had
      sought medical help in the hope of having their bodies altered to correspond to
      their identity, but the Clinic psychiatrists insisted on seeing the problem in
      psychiatric terms and did not recommend surgical or hormonal treatments in most
      cases. This attitude would gradually change over the course of the 1970s and
      1980s.

PMID- 29199928
TI  - Finding a Space for Women: The British Medical Association and Women Doctors in
      Australia, 1880-1939.
AB  - This paper examines the experiences of women in one professional organisation -
      the British Medical Association in Australia - during a significant period in the
      development of such bodies. In doing so it offers an opportunity to consider the
      relationship between professional societies and the construction of a gendered
      profession. For the medical profession in particular the time-frame of this
      study, from the 1880s to the 1930s, has been regarded by scholars as especially
      important. In this period various features of medical professionalism came to
      prominence: the status and authority of doctors, the processes of formally
      registering medical credentials, and the scope and cohesiveness of professional
      associations. Taking the third of these themes, the current paper extends
      previous analyses by uniting gender with history and medicine as the central
      point of examination, in order to evaluate the changing and contested positions
      of women within the profession. In this way we not only demonstrate how the
      history of professional societies can reveal the diverse beliefs and shifting
      priorities of their members, but also contribute to explaining the remarkable
      persistence of gendered differences in the medical profession.

PMID- 29199929
TI  - Healing a Sick World: Psychiatric Medicine and the Atomic Age.
AB  - The onset of nuclear warfare in Hiroshima and Nagasaki had far-reaching
      implications for the world of medicine. The study of the A-bomb and its
      implications led to the launching of new fields and avenues of research, most
      notably in genetics and radiation studies. Far less understood and under-studied
      was the impact of nuclear research on psychiatric medicine. Psychological
      research, however, was a major focus of post-war military and civilian research
      into the bomb. This research and the perceived revolutionary impact of atomic
      energy and warfare on society, this paper argues, played an important role in the
      global development of post-war psychiatry. Focusing on psychiatrists in North
      America, Japan and the United Nations, this paper examines the reaction of the
      profession to the nuclear age from the early post-war period to the mid 1960s.
      The way psychiatric medicine related to atomic issues, I argue, shifted
      significantly between the immediate post-war period and the 1960s. While the
      early post-war psychiatrists sought to help society deal with and adjust to the
      new nuclear reality, later psychiatrists moved towards a more radical position
      that sought to resist the establishment's efforts to normalise the bomb and
      nuclear energy. This shift had important consequences for research into the
      psychological trauma suffered by victims of nuclear warfare, which, ultimately,
      together with other research into the impact of war and systematic violence, led
      to our current understanding of Post-Traumatic Stress Disorder (PTSD).

PMID- 29199942
TI  - Criminocorpus: Browsing through the French History of Crime and Medicine.

PMID- 29199930
TI  - Lechebnaia pedagogika: The Concept and Practice of Therapy in Russian
      Defectology, c. 1880-1936.
AB  - Therapy is not simply a domain or form of medical practice, but also a metaphor
      for and a performance of medicine, of its functions and status, of its
      distinctive mode of action upon the world. This article examines medical
      treatment or therapy (in Russian lechenie), as concept and practice, in what came
      to be known in Russia as defectology (defektologiia) - the discipline and
      occupation concerned with the study and care of children with developmental
      pathologies, disabilities and special needs. Defectology formed an impure,
      occupationally ambiguous, therapeutic field, which emerged between different
      types of expertise in the niche populated by children considered 'difficult to
      cure', 'difficult to teach', and 'difficult to discipline'. The article follows
      the multiple genealogy of defectological therapeutics in the medical, pedagogical
      and juridical domains, across the late tsarist and early Soviet eras. It argues
      that the distinctiveness of defectological therapeutics emerged from the tensions
      between its biomedical, sociopedagogical and moral-juridical framings, resulting
      in ambiguous hybrid forms, in which medical treatment strategically interlaced
      with education or upbringing, on the one hand, and moral correction, on the
      other.

PMID- 29199944
TI  - MDH volume 62 Issue 1 Cover and Back matter.

PMID- 29199945
TI  - Evaluating mental health service use during and after emergency department visits
      in a multisite cohort of Canadian children and youth.
AB  - OBJECTIVES: The goal of this study was to examine the mental health needs of
      children and youth who present to the emergency department (ED) for mental health
      care and to describe the type of, and satisfaction with, follow-up mental health
      services accessed. METHODS: A 6-month to 1.5-year prospective cohort study was
      conducted in three Canadian pediatric EDs and one general ED, with a 1-month
      follow-up post-ED discharge. Measures included 1) clinician rating of mental
      health needs, 2) patient and caregiver self-reports of follow-up services, and 3)
      interviews regarding follow-up satisfaction. Data analysis included descriptive
      statistics and the Fisher's exact test to compare sites. RESULTS: The cohort
      consisted of 373 children and youth (61.1% female; mean age 15.1 years, 1.5
      standard deviation). The main reason for ED presentations was a mental health
      crisis. The three most frequent areas of need requiring action were mood (43.8%),
      suicide risk (37.4%), and parent-child relational problems (34.6%). During the ED
      visit, 21.6% of patients received medical clearance, 40.9% received a psychiatric
      consult, and 19.4% were admitted to inpatient psychiatric care. At the 1-month
      post-ED visit, 84.3% of patients/caregivers received mental health follow-up.
      Ratings of service recommendations were generally positive, as 60.9% of patients
      obtained the recommended follow-up care and 13.9% were wait-listed. CONCLUSIONS:
      Children and youth and their families presenting to the ED with mental health
      needs had substantial clinical morbidity, were connected with services, were
      satisfied with their ED visit, and accessed follow-up care within 1-month with
      some variability.

PMID- 29199946
TI  - Stimulation of hair follicle stem cell proliferation through an IL-1 dependent
      activation of gammadeltaT-cells.
AB  - The cutaneous wound-healing program is a product of a complex interplay among
      diverse cell types within the skin. One fundamental process that is mediated by
      these reciprocal interactions is the mobilization of local stem cell pools to
      promote tissue regeneration and repair. Using the ablation of epidermal caspase-8
      as a model of wound healing in Mus musculus, we analyzed the signaling components
      responsible for epithelial stem cell proliferation. We found that IL-1alpha and
      IL-7 secreted from keratinocytes work in tandem to expand the activated
      population of resident epidermal gammadeltaT-cells. A downstream effect of
      activated gammadeltaT-cells is the preferential proliferation of hair follicle
      stem cells. By contrast, IL-1alpha-dependent stimulation of dermal fibroblasts
      optimally stimulates epidermal stem cell proliferation. These findings provide
      new mechanistic insights into the regulation and function of epidermal cell
      immune cell interactions and into how components that are classically associated
      with inflammation can differentially influence distinct stem cell niches within a
      tissue.

PMID- 29199949
TI  - How the brain controls urination.
AB  - Coordination between the brainstem and the cortex helps to ensure that urination
      occurs at an appropriate time.

PMID- 29199947
TI  - Neurophysiological evidence of efference copies to inner speech.
AB  - Efference copies refer to internal duplicates of movement-producing neural
      signals. Their primary function is to predict, and often suppress, the sensory
      consequences of willed movements. Efference copies have been almost exclusively
      investigated in the context of overt movements. The current electrophysiological
      study employed a novel design to show that inner speech - the silent production
      of words in one's mind - is also associated with an efference copy. Participants
      produced an inner phoneme at a precisely specified time, at which an audible
      phoneme was concurrently presented. The production of the inner phoneme resulted
      in electrophysiological suppression, but only if the content of the inner phoneme
      matched the content of the audible phoneme. These results demonstrate that inner
      speech - a purely mental action - is associated with an efference copy with
      detailed auditory properties. These findings suggest that inner speech may
      ultimately reflect a special type of overt speech.

PMID- 29199948
TI  - Brainstem network dynamics underlying the encoding of bladder information.
AB  - Urodynamic status must interact with arousal and attentional processes so that
      voiding occurs under appropriate conditions. To elucidate the central encoding of
      this visceral demand, multisite recordings were made within a putative pontine
      cortical micturition circuit from the pontine micturition center (PMC), locus
      coeruleus (LC) and medial prefrontal cortex (mPFC) during cystometry in
      unanesthetized rats. PMC neurons had homogeneous firing patterns, characterized
      by tonic activity and phasic bursts that were temporally associated with distinct
      phases of the micturition cycle. LC and cortical activation became synchronized
      20-30 s prior to micturition. During this pre-micturition interval, a theta
      oscillation developed in the LC, the mPFC desynchronized and LC-mPFC coherence
      increased in the theta frequency range. The temporal offset between the shift in
      LC-mPFC network activity and micturition may allow time to disengage from ongoing
      behaviors unrelated to micturition and initiate specific voiding behaviors so
      that micturition occurs in environmentally and socially appropriate conditions.

PMID- 29199950
TI  - Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR
      complex 1 through Rag GTPases.
AB  - TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that
      promotes cellular macromolecular synthesis and suppresses autophagy. Amino-acid
      induced activation of mammalian TORC1 is initiated by its recruitment to the
      RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes
      through the Ragulator complex. We have identified in the model organism
      Schizosaccharomyces pombe a Ragulator-like complex that tethers the Gtr1-Gtr2 Rag
      heterodimer to the membranes of vacuoles, the lysosome equivalent in yeasts.
      Unexpectedly, the Ragulator-Rag complex is not required for the vacuolar
      targeting of TORC1, but the complex plays a crucial role in attenuating TORC1
      activity independently of the Tsc1-Tsc2 complex, a known negative regulator of
      TORC1 signaling. The GATOR1 complex, which functions as Gtr1 GAP, is essential
      for the TORC1 attenuation by the Ragulator-Rag complex, suggesting that Gtr1GDP
      Gtr2 on vacuolar membranes moderates TORC1 signaling for optimal cellular
      response to nutrients.

PMID- 29199951
TI  - Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone
      growth by fibroblast growth factor.
AB  - Activating mutations in fibroblast growth factor (FGF) receptor 3 and
      inactivating mutations in the NPR2 guanylyl cyclase both cause severe short
      stature, but how these two signaling systems interact to regulate bone growth is
      poorly understood. Here, we show that bone elongation is increased when NPR2
      cannot be dephosphorylated and thus produces more cyclic GMP. By developing an in
      vivo imaging system to measure cyclic GMP production in intact tibia, we show
      that FGF-induced dephosphorylation of NPR2 decreases its guanylyl cyclase
      activity in growth plate chondrocytes in living bone. The dephosphorylation
      requires a PPP-family phosphatase. Thus FGF signaling lowers cyclic GMP
      production in the growth plate, which counteracts bone elongation. These results
      define a new component of the signaling network by which activating mutations in
      the FGF receptor inhibit bone growth.

PMID- 29199952
TI  - Cryo-EM structures reveal specialization at the myosin VI-actin interface and a
      mechanism of force sensitivity.
AB  - Despite extensive scrutiny of the myosin superfamily, the lack of high-resolution
      structures of actin-bound states has prevented a complete description of its
      mechanochemical cycle and limited insight into how sequence and structural
      diversification of the motor domain gives rise to specialized functional
      properties. Here we present cryo-EM structures of the unique minus-end directed
      myosin VI motor domain in rigor (4.6 A) and Mg-ADP (5.5 A) states bound to F
      actin. Comparison to the myosin IIC-F-actin rigor complex reveals an almost
      complete lack of conservation of residues at the actin-myosin interface despite
      preservation of the primary sequence regions composing it, suggesting an
      evolutionary path for motor specialization. Additionally, analysis of the
      transition from ADP to rigor provides a structural rationale for force
      sensitivity in this step of the mechanochemical cycle. Finally, we observe
      reciprocal rearrangements in actin and myosin accompanying the transition between
      these states, supporting a role for actin structural plasticity during force
      generation by myosin VI.

PMID- 29199953
TI  - Synaptic and peptidergic connectome of a neurosecretory center in the annelid
      brain.
AB  - Neurosecretory centers in animal brains use peptidergic signaling to influence
      physiology and behavior. Understanding neurosecretory center function requires
      mapping cell types, synapses, and peptidergic networks. Here we use transmission
      electron microscopy and gene expression mapping to analyze the synaptic and
      peptidergic connectome of an entire neurosecretory center. We reconstructed 78
      neurosecretory neurons and mapped their synaptic connectivity in the brain of
      larval Platynereis dumerilii, a marine annelid. These neurons form an anterior
      neurosecretory center expressing many neuropeptides, including hypothalamic
      peptide orthologs and their receptors. Analysis of peptide-receptor pairs in
      spatially mapped single-cell transcriptome data revealed sparsely connected
      networks linking specific neuronal subsets. We experimentally analyzed one
      peptide-receptor pair and found that a neuropeptide can couple neurosecretory and
      synaptic brain signaling. Our study uncovered extensive networks of peptidergic
      signaling within a neurosecretory center and its connection to the synaptic
      brain.

PMID- 29199954
TI  - Shaping of inner ear sensory organs through antagonistic interactions between
      Notch signalling and Lmx1a.
AB  - The mechanisms of formation of the distinct sensory organs of the inner ear and
      the non-sensory domains that separate them are still unclear. Here, we show that
      several sensory patches arise by progressive segregation from a common prosensory
      domain in the embryonic chicken and mouse otocyst. This process is regulated by
      mutually antagonistic signals: Notch signalling and Lmx1a. Notch-mediated lateral
      induction promotes prosensory fate. Some of the early Notch-active cells,
      however, are normally diverted from this fate and increasing lateral induction
      produces misshapen or fused sensory organs in the chick. Conversely Lmx1a (or
      cLmx1b in the chick) allows sensory organ segregation by antagonizing lateral
      induction and promoting commitment to the non-sensory fate. Our findings
      highlight the dynamic nature of sensory patch formation and the labile character
      of the sensory-competent progenitors, which could have facilitated the emergence
      of new inner ear organs and their functional diversification in the course of
      evolution.

PMID- 29199955
TI  - A selective role for ventromedial subthalamic nucleus in inhibitory control.
AB  - The subthalamic nucleus (STN) is hypothesized to play a central role in the rapid
      stopping of movement in reaction to a stop signal. Single-unit recording evidence
      for such a role is sparse, however, and it remains uncertain how that role
      relates to the disparate functions described for anatomic subdivisions of the
      STN. Here we address that gap in knowledge using non-human primates and a task
      that distinguishes reactive and proactive action inhibition, switching and
      skeletomotor functions. We found that specific subsets of STN neurons have
      activity consistent with causal roles in reactive action stopping or switching.
      Importantly, these neurons were strictly segregated to a ventromedial region of
      STN. Neurons in other subdivisions encoded task dimensions such as movement per
      se and proactive control. We propose that the involvement of STN in reactive
      control is restricted to its ventromedial portion, further implicating this STN
      subdivision in impulse control disorders.

PMID- 29199956
TI  - Computationally-driven identification of antibody epitopes.
AB  - Understanding where antibodies recognize antigens can help define mechanisms of
      action and provide insights into progression of immune responses. We investigate
      the extent to which information about binding specificity implicitly encoded in
      amino acid sequence can be leveraged to identify antibody epitopes. In
      computationally-driven epitope localization, possible antibody-antigen binding
      modes are modeled, and targeted panels of antigen variants are designed to
      experimentally test these hypotheses. Prospective application of this approach to
      two antibodies enabled epitope localization using five or fewer variants per
      antibody, or alternatively, a six-variant panel for both simultaneously.
      Retrospective analysis of a variety of antibodies and antigens demonstrated an
      almost 90% success rate with an average of three antigen variants, further
      supporting the observation that the combination of computational modeling and
      protein design can reveal key determinants of antibody-antigen binding and enable
      efficient studies of collections of antibodies identified from polyclonal samples
      or engineered libraries.

PMID- 29199957
TI  - The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic
      function and contextual memory.
AB  - Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic
      transmission and plasticity. AMPAR auxiliary proteins regulate receptor
      trafficking, and modulate receptor mobility and its biophysical properties. The
      AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs
      in artificial expression systems, but it is unknown whether Shisa7 has a
      functional role in glutamatergic synapses. We show that Shisa7 physically
      interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion
      resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic
      expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term
      potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed
      a specific deficit in contextual fear memory, both short-term and long-term after
      conditioning, whereas auditory fear memory and anxiety-related behavior were
      normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel
      kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory
      recall.

PMID- 29199960
TI  - Update on the Genetic Basis of Drug Hypersensitivity Reactions.
AB  - Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to
      medicines in predisposed individuals. They represent a major health problem owing
      to the number of patients affected and the severity of the clinical conditions
      they can induce. In addition to environmental factors, the underlying mechanisms
      of DHRs are also influenced by genetic factors, although considerable gaps remain
      in our knowledge. Therefore, further study of the genetics of DHRs is necessary
      to shed light on their underlying mechanisms. In this manuscript, we provide an
      update on the genetic basis of the most frequent types of DHRs, including those
      mediated by immunological and nonimmunological mechanisms. For the first group,
      we will focus on immediate reactions to beta-lactam antibiotics, which are
      associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen
      presentation (HLA-DRA), and nonimmediate reactions to allopurinol,
      anticonvulsants, antibiotics, and antiretrovirals, which are often associated
      with polymorphisms in the HLA system. For the second group, we will focus on
      nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic
      variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5,
      ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest
      for medical practitioners from a range of disciplines who come across these
      reactions in their clinical practice, as well as for allergologists.

PMID- 29199958
TI  - LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1
      mRNA stability in human cells.
AB  - Cyclin D1 is a critical regulator of cell cycle progression and works at the G1
      to S-phase transition. Here, we report the isolation and characterization of the
      novel c-Myc-regulated lncRNA LAST (LncRNA-Assisted Stabilization of Transcripts),
      which acts as a CCND1 mRNA stabilizer. Mechanistically, LAST was shown to
      cooperate with CNBP to bind to the 5'UTR of CCND1 mRNA to protect against
      possible nuclease targeting. In addition, data from CNBP RIP-seq and LAST RNA-seq
      showed that CCND1 mRNA might not be the only target of LAST and CNBP; three
      additional mRNAs were shown to be post-transcriptional targets of LAST and CNBP.
      In a xenograft model, depletion of LAST diminished and ectopic expression of LAST
      induced tumor formation, which are suggestive of its oncogenic function. We thus
      report a previously unknown lncRNA involved in the fine-tuned regulation of CCND1
      mRNA stability, without which CCND1 exhibits, at most, partial expression.

PMID- 29199961
TI  - Airway Epithelium Plays a Leading Role in the Complex Framework Underlying
      Respiratory Allergy.
AB  - Airway epithelium is the cellular structure with the greatest surface exposed to
      a plethora of environmental airborne substances, including microorganisms,
      respiratory viruses, air pollutants, and allergens. In addition to being a
      protective physical barrier at the air-liquid interface, the airway epithelium
      acts as an effective chemical and immunological barrier that plays a crucial role
      in orchestrating the immune response in the lungs, by supporting the activation,
      recruitment, and mobilization of immune cells. Airway epithelium dysfunction has
      been clearly associated with various airway inflammatory diseases, such as
      allergic asthma. Although it is not fully understood why a person develops
      respiratory allergy, a growing body of evidence shows that the nature of the
      host's immune response is strongly determined by the state of the airway
      epithelium at the time of contact with the inhaled allergen. Our review
      highlights the physiological state of airway epithelium as a key element in the
      development of allergy and, particularly, in exacerbation of asthma. We review
      the role of physiological oxidants as signaling molecules in lung biology and
      allergic diseases and examine how high exposure to air pollutants (eg, cigarette
      smoke and diesel particles) can contribute to the increased incidence of
      respiratory allergy and exacerbation of the disease.

PMID- 29199959
TI  - Single-cell transcriptome analysis of avian neural crest migration reveals
      signatures of invasion and molecular transitions.
AB  - Neural crest cells migrate throughout the embryo, but how cells move in a
      directed and collective manner has remained unclear. Here, we perform the first
      single-cell transcriptome analysis of cranial neural crest cell migration at
      three progressive stages in chick and identify and establish hierarchical
      relationships between cell position and time-specific transcriptional signatures.
      We determine a novel transcriptional signature of the most invasive neural crest
      Trailblazer cells that is consistent during migration and enriched for
      approximately 900 genes. Knockdown of several Trailblazer genes shows significant
      but modest changes to total distance migrated. However, in vivo expression
      analysis by RNAscope and immunohistochemistry reveals some salt and pepper
      patterns that include strong individual Trailblazer gene expression in cells
      within other subregions of the migratory stream. These data provide new insights
      into the molecular diversity and dynamics within a neural crest cell migratory
      stream that underlie complex directed and collective cell behaviors.

PMID- 29199962
TI  - Contact Sensitization in Patients With Lower Leg Dermatitis, Chronic Venous
      Insufficiency, and/or Chronic Leg Ulcer: Assessment of the Clinical Relevance of
      Contact Allergens.

PMID- 29199963
TI  - Food Protein-Induced Enterocolitis Syndrome in Response to Quail's Egg in a Child
      Without Hen's Egg Allergy.

PMID- 29199964
TI  - A Case of Hypocomplementemic Urticarial Vasculitis Syndrome Successfully Treated
      With Omalizumab.

PMID- 29199965
TI  - Is Saccharomyces boulardii Really Safe?

PMID- 29199966
TI  - Occupational Asthma and Urticaria in a Fishmonger Due to Creatine Kinase, a Cross
      Reactive Fish Allergen.

PMID- 29199967
TI  - Different Skin Prick Test Sensitization Patterns Do Not Influence the Response to
      Omalizumab in Severe Asthma.

PMID- 29199968
TI  - IgE-Binding Aldolases From Artemia and Mysis Species Causing Respiratory Allergy
      to Aquarium Fish Food.

PMID- 29199969
TI  - Dysregulated Innate Lymphocytes in Patients With Primary Antibody Deficiency
      Treated With Intravenous Immunoglobulin.

PMID- 29199970
TI  - What Could the Role of Can f 5 Allergen Be in Dog-Sensitized Patients in "Real
      Life"?

PMID- 29199971
TI  - Collagen scaffolds tethered with bFGF promote corpus spongiosum regeneration in a
      beagle model.
AB  - Regeneration of the corpus spongiosum helps prevent complications following
      urethral reconstruction, but currently there is a lack of effective therapeutic
      methods in clinic. In previous studies, we fabricated a fusion protein collagen
      binding domain (CBD)-basic fibroblast growth factor (bFGF) that specifically
      binds to and releases from collagen biomaterials. We demonstrated that CBD-bFGF
      could promote angiogenesis and tissue regeneration in vivo. In this study, we
      established a beagle model with extensive urethral defects, and reconstructed the
      defects with collagen biomaterials that were unmodified or modified with CBD
      bFGF. The results demonstrate that CBD-bFGF promotes corpus spongiosum
      regeneration resulting in improved outcomes following urethral reconstruction.
      Modifying collagen biomaterials with CBD-bFGF may represent an effective strategy
      for urethral substitution in urethral reconstruction.

PMID- 29199972
TI  - Transmission XMCD-PEEM imaging of an engineered vertical FEBID cobalt nanowire
      with a domain wall.
AB  - Using focused electron-beam-induced deposition, we fabricate a vertical, platinum
      coated cobalt nanowire with a controlled three-dimensional structure. The latter
      is engineered to feature bends along the height: these are used as pinning sites
      for domain walls, which are obtained at remanence after saturation of the
      nanostructure in a horizontally applied magnetic field. The presence of domain
      walls is investigated using x-ray magnetic circular dichroism (XMCD) coupled to
      photoemission electron microscopy (PEEM). The vertical geometry of our sample
      combined with the low incidence of the x-ray beam produce an extended wire shadow
      which we use to recover the wire's magnetic configuration. In this transmission
      configuration, the whole sample volume is probed, thus circumventing the
      limitation of PEEM to surfaces. This article reports on the first study of
      magnetic nanostructures standing perpendicular to the substrate with XMCD-PEEM.
      The use of this technique in shadow mode enabled us to confirm the presence of a
      domain wall without direct imaging of the nanowire.

PMID- 29199973
TI  - Thermal conductivity anisotropy in holey silicon nanostructures and its impact on
      thermoelectric cooling.
AB  - Artificial nanostructures have improved prospects of thermoelectric systems by
      enabling selective scattering of phonons and demonstrating significant thermal
      conductivity reductions. While the low thermal conductivity provides necessary
      temperature gradients for thermoelectric conversion, the heat generation is
      detrimental to electronic systems where high thermal conductivity are preferred.
      The contrasting needs of thermal conductivity are evident in thermoelectric
      cooling systems, which call for a fundamental breakthrough. Here we show a
      silicon nanostructure with vertically etched holes, or holey silicon, uniquely
      combines the low thermal conductivity in the in-plane direction and the high
      thermal conductivity in the cross-plane direction, and that the anisotropy is
      ideal for lateral thermoelectric cooling. The low in-plane thermal conductivity
      due to substantial phonon boundary scattering in small necks sustains large
      temperature gradients for lateral Peltier junctions. The high cross-plane thermal
      conductivity due to persistent long-wavelength phonons effectively dissipates
      heat from a hot spot to the on-chip cooling system. Our scaling analysis based on
      spectral phonon properties captures the anisotropic size effects in holey silicon
      and predicts the thermal conductivity anisotropy ratio up to 20. Our numerical
      simulations demonstrate the thermoelectric cooling effectiveness of holey silicon
      is at least 30% greater than that of high-thermal-conductivity bulk silicon and
      400% greater than that of low-thermal-conductivity chalcogenides; these results
      contrast with the conventional perception preferring either high or low thermal
      conductivity materials. The thermal conductivity anisotropy is even more
      favorable in laterally confined systems and will provide effective thermal
      management solutions for advanced electronics.

PMID- 29199974
TI  - Enhancement of fluorescent emission in photonic crystal film and application in
      photocatalysis.
AB  - Fluorescent photonic crystal films composed of monodisperse NaYF4:15Yb,0.5Tm@SiO2
      (where 15 and 0.5 represent the mole percentage of reactants) core-shell spheres
      were successfully fabricated and applied in photocatalysis. The core-shell
      spheres were prepared using a modified Stober method, and fluorescent photonic
      crystal films were fabricated via a simple self-assembly method. The
      morphologies, structures and upconversion fluorescent properties of the
      fluorescent photonic crystal films with different photonic band gaps were
      characterized. Moreover, their photocatalytic capability in decomposing rhodamine
      B using near-infrared light was studied. Results indicate that the band edge
      effect plays a critical role in the enhancement of short wave emission intensity
      of fluorescent photonic crystal films. Specifically, in comparison to the
      reference sample without a band edge effect, the 363 nm emission intensity was
      enhanced by 5.97 times, while the percentage of UV upconversion emission was
      improved by 6.23%. In addition, the 451 nm emission intensity was enhanced by
      5.81 times, and the percentage of visible upconversion emission was improved by
      8.88%. Furthermore, fluorescent photonic crystal films with enhanced short wave
      emission exhibited great photocatalytic performance in the degradation of
      rhodamine B aqueous solutions under near-infrared light.

PMID- 29199975
TI  - Carbon nanotube conditioning part 1-effect of interwall interaction on the
      electronic band gap of double-walled carbon nanotubes.
AB  - Ab initio density functional theory simulations were used to calculate the
      electronic structure and the total energy of double-walled carbon nanotubes
      (DWCNTs). The relaxed configurations studied were uncapped, infinitely-long
      zigzag@zigzag double-walled carbon nanotubes. The lowest energy configuration was
      found to correspond to an interwall distance of 0.35 nm, except for the
      configurations with inner tube chiral indices (5,0), (6,0) and (7,0). The largest
      binding energies were found to correspond to a 0.35 nm interwall distance for all
      the DWCNT configurations studied, and increasing with DWCNT average diameter. In
      terms of the effect of the interwall interaction on the electronic band gap of
      DWCNTs, four regions of band gap were obtained which were termed: zero band gap,
      narrow band gap, small band gap, and medium band gap regions. These regions offer
      the possibility to first tune the electronic band gap to a region with a desired
      range, and further tune that choice within the region itself by varying the
      interwall distance. It was also found that zigzag@zigzag DWCNTs with outer tube
      leading chiral index n = 3k + 1 or n = 3k + 2 (k being an integer) follow, as a
      general trend, an inversely proportional relation of the electronic band gap with
      respect to the average diameter.

PMID- 29199977
TI  - Structural insight into the rearrangement of the switch I region in GTP-bound
      G12A K-Ras.
AB  - K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism,
      is activated when it undergoes a conformation change upon binding GTP and is
      deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is
      accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation
      approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP
      hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in
      complex with GDP, GTP, GTPgammaS and GppNHp, and of Q61A K-Ras in complex with
      GDP, are reported. In the G12A K-Ras-GTP complex, the switch I region undergoes a
      significant reorganization such that the Tyr32 side chain points towards the GTP
      binding pocket and forms a hydrogen bond to the GTP gamma-phosphate, effectively
      stabilizing GTP in its precatalytic state, increasing the activation energy
      required to reach the transition state and contributing to the reduced intrinsic
      GTPase activity of G12A K-Ras mutants.

PMID- 29199976
TI  - Hydrogen bonds are a primary driving force for de novo protein folding.
AB  - The protein-folding mechanism remains a major puzzle in life science. Purified
      soluble activation-induced cytidine deaminase (AID) is one of the most difficult
      proteins to obtain. Starting from inclusion bodies containing a C-terminally
      truncated version of AID (residues 1-153; AID153), an optimized in vitro folding
      procedure was derived to obtain large amounts of AID153, which led to crystals
      with good quality and to final structural determination. Interestingly, it was
      found that the final refolding yield of the protein is proline residue-dependent.
      The difference in the distribution of cis and trans configurations of proline
      residues in the protein after complete denaturation is a major determining factor
      of the final yield. A point mutation of one of four proline residues to an
      asparagine led to a near-doubling of the yield of refolded protein after complete
      denaturation. It was concluded that the driving force behind protein folding
      could not overcome the cis-to-trans proline isomerization, or vice versa, during
      the protein-folding process. Furthermore, it was found that successful refolding
      of proteins optimally occurs at high pH values, which may mimic protein folding
      in vivo. It was found that high pH values could induce the polarization of
      peptide bonds, which may trigger the formation of protein secondary structures
      through hydrogen bonds. It is proposed that a hydrophobic environment coupled
      with negative charges is essential for protein folding. Combined with our earlier
      discoveries on protein-unfolding mechanisms, it is proposed that hydrogen bonds
      are a primary driving force for de novo protein folding.

PMID- 29199978
TI  - Approaches to ab initio molecular replacement of alpha-helical transmembrane
      proteins.
AB  - alpha-Helical transmembrane proteins are a ubiquitous and important class of
      proteins, but present difficulties for crystallographic structure solution. Here,
      the effectiveness of the AMPLE molecular replacement pipeline in solving alpha
      helical transmembrane-protein structures is assessed using a small library of
      eight ideal helices, as well as search models derived from ab initio models
      generated both with and without evolutionary contact information. The ideal
      helices prove to be surprisingly effective at solving higher resolution
      structures, but ab initio-derived search models are able to solve structures that
      could not be solved with the ideal helices. The addition of evolutionary contact
      information results in a marked improvement in the modelling and makes additional
      solutions possible.

PMID- 29199979
TI  - A standardized technique for high-pressure cooling of protein crystals.
AB  - Cryogenic temperatures slow down secondary radiation damage during data
      collection from macromolecular crystals. In 1973, cooling at high pressure was
      identified as a method for cryopreserving crystals in their mother liquor
      [Thomanek et al. (1973). Acta Cryst. A29, 263-265]. Results from different groups
      studying different crystal systems indicated that the approach had merit,
      although difficulties in making the process work have limited its widespread use.
      Therefore, a simplified and reliable technique has been developed termed high
      pressure cooling (HPC). An essential requirement for HPC is to protect crystals
      in capillaries. These capillaries form part of new sample holders with SPINE
      standard dimensions. Crystals are harvested with the capillary, cooled at high
      pressure (220 MPa) and stored in a cryovial. This system also allows the usage of
      the standard automation at the synchrotron. Crystals of hen egg-white lysozyme
      and concanavalin A have been successfully cryopreserved and yielded data sets to
      resolutions of 1.45 and 1.35 A, respectively. Extensive work has been performed
      to define the useful working range of HPC in capillaries with 250 um inner
      diameter. Three different 96-well crystallization screens that are most
      frequently used in our crystallization facility were chosen to study the
      formation of amorphous ice in this cooling setup. More than 89% of the screening
      solutions were directly suitable for HPC. This achievement represents a drastic
      improvement for crystals that suffered from cryoprotection or were not previously
      eligible for cryoprotection.

PMID- 29199980
TI  - Molecular architectures of benzoic acid-specific type III polyketide synthases.
AB  - Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct
      clade of type III polyketide synthases (PKSs) that use benzoic acid-derived
      substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an
      endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses
      indicate that the residues responsible for the functional diversification of type
      III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a
      better understanding of structure-function relationships within the type III PKS
      family, the crystal structures of biphenyl synthase from Malus * domestica and
      benzophenone synthase from Hypericum androsaemum were compared with the structure
      of an archetypal type III PKS: chalcone synthase from Malus * domestica. Both
      biphenyl synthase and benzophenone synthase contain mutations that reshape their
      active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the
      binding of small hydrophobic substrates. The active-site cavities of biphenyl
      synthase and benzophenone synthase also contain a novel pocket associated with
      their chain-elongation and cyclization reactions. Collectively, these results
      illuminate structural determinants of benzoic acid-specific type III PKSs and
      expand the understanding of the evolution of specialized metabolic pathways in
      plants.

PMID- 29199981
TI  - Solving the scalability issue in quantum-based refinement: Q|R#1.
AB  - Accurately refining biomacromolecules using a quantum-chemical method is
      challenging because the cost of a quantum-chemical calculation scales
      approximately as nm, where n is the number of atoms and m (>=3) is based on the
      quantum method of choice. This fundamental problem means that quantum-chemical
      calculations become intractable when the size of the system requires more
      computational resources than are available. In the development of the software
      package called Q|R, this issue is referred to as Q|R#1. A divide-and-conquer
      approach has been developed that fragments the atomic model into small manageable
      pieces in order to solve Q|R#1. Firstly, the atomic model of a crystal structure
      is analyzed to detect noncovalent interactions between residues, and the results
      of the analysis are represented as an interaction graph. Secondly, a graph
      clustering algorithm is used to partition the interaction graph into a set of
      clusters in such a way as to minimize disruption to the noncovalent interaction
      network. Thirdly, the environment surrounding each individual cluster is analyzed
      and any residue that is interacting with a particular cluster is assigned to the
      buffer region of that particular cluster. A fragment is defined as a cluster plus
      its buffer region. The gradients for all atoms from each of the fragments are
      computed, and only the gradients from each cluster are combined to create the
      total gradients. A quantum-based refinement is carried out using the total
      gradients as chemical restraints. In order to validate this interaction graph
      based fragmentation approach in Q|R, the entire atomic model of an amyloid cross
      beta spine crystal structure (PDB entry 2oNA) was refined.

PMID- 29199982
TI  - Using more than 801 296 small-molecule crystal structures to aid in protein
      structure refinement and analysis. Addendum.
AB  - An addendum to the Introduction of Cole et al. [(2017), Acta Cryst. D73, 234-239]
      is made to recognize the work of Bricogne, Smart and others in the development of
      methods to make use of Cambridge Structural Database data in protein structure
      solution.

PMID- 29199984
TI  - Structure of the Bacillus anthracis dTDP-L-rhamnose-biosynthetic enzyme dTDP-4
      dehydrorhamnose reductase (RfbD).
AB  - Bacillus anthracis is the causative agent of the deadly disease Anthrax. Its use
      in bioterrorism and its ability to re-emerge have brought renewed interest in
      this organism. B. anthracis is a Gram-positive bacterium that adds L-rhamnose to
      its cell-wall polysaccharides using the activated donor dTDP-beta-L-rhamnose. The
      enzymes involved in the biosynthesis of the activated donor are absent in humans,
      which make them ideal targets for therapeutic development to combat pathogens.
      Here, the 2.65 A resolution crystal structure of the fourth enzyme in the dTDP
      beta-L-rhamnose-biosynthetic pathway from B. anthracis, dTDP-4-dehydro-beta-L
      rhamnose reductase (RfbD), is presented in complex with NADP+. This enzyme
      catalyzes the reduction of dTDP-4-dehydro-beta-L-rhamnose to dTDP-beta-L
      rhamnose. Although the protein was co-crystallized in the presence of Mg2+, the
      protein lacks the conserved residues that coordinate Mg2+.

PMID- 29199985
TI  - Crystal structure of a pyridoxal 5'-phosphate-dependent aspartate racemase
      derived from the bivalve mollusc Scapharca broughtonii.
AB  - Aspartate racemase (AspR) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that
      is responsible for D-aspartate biosynthesis in vivo. To the best of our
      knowledge, this is the first study to report an X-ray crystal structure of a PLP
      dependent AspR, which was resolved at 1.90 A resolution. The AspR derived from
      the bivalve mollusc Scapharca broughtonii (SbAspR) is a type II PLP-dependent
      enzyme that is similar to serine racemase (SR) in that SbAspR catalyzes both
      racemization and dehydration. Structural comparison of SbAspR and SR shows a
      similar arrangement of the active-site residues and nucleotide-binding site, but
      a different orientation of the metal-binding site. Superposition of the
      structures of SbAspR and of rat SR bound to the inhibitor malonate reveals that
      Arg140 recognizes the beta-carboxyl group of the substrate aspartate in SbAspR.
      It is hypothesized that the aromatic proline interaction between the domains,
      which favours the closed form of SbAspR, influences the arrangement of Arg140 at
      the active site.

PMID- 29199986
TI  - A low-cost method for visible fluorescence imaging.
AB  - A wide variety of crystallization solutions are screened to establish conditions
      that promote the growth of a diffraction-quality crystal. Screening these
      conditions requires the assessment of many crystallization plates for the
      presence of crystals. Automated systems for screening and imaging are very
      expensive. A simple approach to imaging trace fluorescently labeled protein
      crystals in crystallization plates has been devised, and can be implemented at a
      cost as low as $50. The proteins beta-lactoglobulin B, trypsin and purified
      concanavalin A (ConA) were trace fluorescently labeled using three different
      fluorescent probes: Cascade Yellow (CY), Carboxyrhodamine 6G (CR) and Pacific
      Blue (PB). A crystallization screening plate was set up using beta-lactoglobulin
      B labeled with CR, trypsin labeled with CY, ConA labeled with each probe, and a
      mixture consisting of 50% PB-labeled ConA and 50% CR-labeled ConA. The wells of
      these plates were imaged using a commercially available macro-imaging lens
      attachment for smart devices that have a camera. Several types of macro lens
      attachments were tested with smartphones and tablets. Images with the highest
      quality were obtained with an iPhone 6S and an AUKEY Ora 10* macro lens.
      Depending upon the fluorescent probe employed and its Stokes shift, a light
      emitting diode or a laser diode was used for excitation. An emission filter was
      used for the imaging of protein crystals labeled with CR and crystals with two
      color fluorescence. This approach can also be used with microscopy systems
      commonly used to observe crystallization plates.

PMID- 29199987
TI  - Structure of the Bacillus anthracis dTDP-L-rhamnose-biosynthetic enzyme dTDP-4
      dehydrorhamnose 3,5-epimerase (RfbC).
AB  - The exosporium layer of Bacillus anthracis spores is rich in L-rhamnose, a common
      bacterial cell-wall component, which often contributes to the virulence of
      pathogens by increasing their adherence and immune evasion. The biosynthetic
      pathway used to form the activated L-rhamnose donor dTDP-L-rhamnose consists of
      four enzymes (RfbA, RfbB, RfbC and RfbD) and is an attractive drug target because
      there are no homologs in mammals. It was found that co-purifying and screening
      RfbC (dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase) from B. anthracis in the
      presence of the other three B. anthracis enzymes of the biosynthetic pathway
      yielded crystals that were suitable for data collection. RfbC crystallized as a
      dimer and its structure was determined at 1.63 A resolution. Two different
      ligands were bound in the protein structure: pyrophosphate in the active site of
      one monomer and dTDP in the other monomer. A structural comparison with RfbC
      homologs showed that the key active-site residues are conserved across kingdoms.

PMID- 29199988
TI  - Swit_4259, an acetoacetate decarboxylase-like enzyme from Sphingomonas wittichii
      RW1.
AB  - The Gram-negative bacterium Sphingomonas wittichii RW1 is notable for its ability
      to metabolize a variety of aromatic hydrocarbons. Not surprisingly, the S.
      wittichii genome contains a number of putative aromatic hydrocarbon-degrading
      gene clusters. One of these includes an enzyme of unknown function, Swit_4259,
      which belongs to the acetoacetate decarboxylase-like superfamily (ADCSF). Here,
      it is reported that Swit_4259 is a small (28.8 kDa) tetrameric ADCSF enzyme that,
      unlike the prototypical members of the superfamily, does not have acetoacetate
      decarboxylase activity. Structural characterization shows that the tertiary
      structure of Swit_4259 is nearly identical to that of the true decarboxylases,
      but there are important differences in the fine structure of the Swit_4259 active
      site that lead to a divergence in function. In addition, it is shown that while
      it is a poor substrate, Swit_4259 can catalyze the hydration of 2-oxo-hex-3
      enedioate to yield 2-oxo-4-hydroxyhexanedioate. It is also demonstrated that
      Swit_4259 has pyruvate aldolase-dehydratase activity, a feature that is common to
      all of the family V ADCSF enzymes studied to date. The enzymatic activity,
      together with the genomic context, suggests that Swit_4259 may be a hydratase
      with a role in the metabolism of an as-yet-unknown hydrocarbon. These data have
      implications for engineering bioremediation pathways to degrade specific
      pollutants, as well as structure-function relationships within the ADCSF in
      general.

PMID- 29199989
TI  - Crystal structure of an anti-idiotype variable lymphocyte receptor.
AB  - Variable lymphocyte receptors (VLRs), the leucine-rich repeat (LRR)-based antigen
      receptors of jawless fish, have great utility in a wide variety of biochemical
      and biological applications, similar to classical Ig-based antibodies. VLR-based
      reagents may be particularly useful when traditional antibodies are not
      available. An anti-idiotype lamprey VLR, VLR39, has previously been identified
      that recognizes the heavy-chain CDR3 of the B-cell receptor (BCR) of a leukemic
      clone from a patient with chronic lymphocytic leukemia (CLL). VLR39 was used
      successfully to track the re-emergence of this clone in the patient following
      chemotherapy. Here, the crystal structure of VLR39 is presented at 1.5 A
      resolution and compared with those of other protein-specific VLRs. VLR39 adopts a
      curved solenoid fold and exhibits substantial structural similarity to other
      protein-binding VLRs. VLR39 has a short LRRCT loop that protrudes outwards away
      from the concave face and is similar to those of its protein-specific VLR
      counterparts. Analysis of the VLR39-BCR interaction by size-exclusion
      chromatography and biolayer interferometry using the scFv version of the BCR
      confirms that VLR39 recognizes the BCR Fv region. Such VLR-based reagents may be
      useful for identifying and monitoring leukemia in CLL patients and in other
      clinical diagnostic assays.

PMID- 29199990
TI  - Meditope-Fab interaction: threading the hole.
AB  - Meditope, a cyclic 12-residue peptide, binds to a unique binding side between the
      light and heavy chains of the cetuximab Fab. In an effort to improve the affinity
      of the interaction, it was sought to extend the side chain of Arg8 in the
      meditope, a residue that is accessible from the other side of the meditope
      binding site, in order to increase the number of interactions. These
      modifications included an n-butyl and n-octyl extension as well as hydroxyl,
      amine and carboxyl substitutions. The atomic structures of the complexes and the
      binding kinetics for each modified meditope indicated that each extension
      threaded through the Fab 'hole' and that the carboxyethylarginine substitution
      makes a favorable interaction with the Fab, increasing the half-life of the
      complex by threefold compared with the unmodified meditope. Taken together, these
      studies provide a basis for the design of additional modifications to enhance the
      overall affinity of this unique interaction.

PMID- 29199991
TI  - Crystal structure of the second fibronectin type III (FN3) domain from human
      collagen alpha1 type XX.
AB  - Collagen alpha1 type XX, which contains fibronectin type III (FN3) repeats
      involving six FN3 domains (referred to as the FN#1-FN#6 domains), is an unusual
      member of the fibril-associated collagens with interrupted triple helices (FACIT)
      subfamily of collagens. The results of standard protein BLAST suggest that the
      FN3 repeats might contribute to collagen alpha1 type XX acting as a cytokine
      receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains
      have been determined. To obtain further structural evidence to understand the
      relationship between the structure and function of the FN3 repeats from collagen
      alpha1 type XX, the crystal structure of the FN#2 domain from human collagen
      alpha1 type XX (residues Pro386-Pro466; referred to as FN2-HCXX) was solved at
      2.5 A resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like
      fold containing a beta-sandwich structure, which is formed by a three-stranded
      beta-sheet (beta1, beta2 and beta5) packed onto a four-stranded beta-sheet
      (beta3, beta4, beta6 and beta7). Two consensus domains, tencon and fibcon, are
      structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal
      fibronectin, is the closest structural analogue of FN2-HCXX derived from a
      naturally occurring sequence. Based solely on the structural similarity of FN2
      HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats
      in collagen alpha1 type XX cannot be identified.

PMID- 29199992
TI  - The Pseudomonas syringae pv. actinidiae chemoreceptor protein F (PscF)
      periplasmic sensor domain: cloning, purification and X-ray crystallographic
      analysis.
AB  - Nitrate- and nitrite-sensing (NIT) domains are found associated with a wide
      variety of bacterial receptors, including chemoreceptors. However, the structure
      of a chemoreceptor-associated NIT domain has not yet been characterized.
      Recently, a chemoreceptor named PscF was identified from the plant pathogen
      Pseudomonas syringae pv. actinidiae that is predicted to contain a periplasmic
      NIT domain. The PscF sensor domain (PscF-SD; residues 42-332) was cloned into an
      appropriate expression vector, recombinantly produced in Escherichia coli BL21
      Gold(DE3) cells and purified via immobilized metal-affinity and size-exclusion
      chromatography. Purified PscF-SD was screened for crystallization; the best
      crystal diffracted to a maximum resolution of 1.46 A in space group P212121.
      However, the data could not be phased using the only available NIT-domain
      structure (Klebsiella oxytoca NasR; PDB entry 4akk) as the search model.
      Therefore, a data set from a selenomethionine-labelled protein crystal was also
      collected. The selenomethionine-labelled protein crystal diffracted to a
      resolution of 2.46 A in space group P212121. These data will be used to attempt
      to solve the structure using the single-wavelength anomalous diffraction
      technique. The structure is expected to provide insights into the ligand
      specificity of NIT domains and the role of NIT domains in chemotaxis.

PMID- 29199993
TI  - Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii.
AB  - Methyltransferases (MTs) are enzymes involved in methylation that are needed to
      perform cellular processes such as biosynthesis, metabolism, gene expression,
      protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine
      (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The
      crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution
      of 2.1 A using X-ray diffraction. The monomeric structure consists of a Rossmann
      like fold (domain I) and a substrate-binding domain (domain II). The cofactor
      (SAM) molecule binds at the interface between adjacent subunits, presumably near
      to the active site(s) of the enzyme. The observed dimeric state might be
      important for the catalytic function of the enzyme.

PMID- 29199994
TI  - DNA-binding domain of myelin-gene regulatory factor: purification,
      crystallization and X-ray analysis. Corrigendum.
AB  - An extra affiliation is added for the authors of the article by Wu et al.
      [(2017), Acta Cryst. F73, 393-397].

PMID- 29199995
TI  - Rare mutations provide unique insight into oncogenic potential of STAT
      transcription factors.
AB  - The inappropriate activation of transcription factors, including STATs, is known
      to promote tumor initiation and progression. The most common mechanisms of
      misregulation lead to constitutive activation of WT STATs. However, the recent
      discovery of rare STAT mutations in hematopoietic malignancies suggests that STAT
      mutants may be oncogenic. In this issue of the JCI, Pham et al. use a transgenic
      mouse model to demonstrate that STAT5BN642H is sufficient for the development of
      T cell neoplasia. This study, along with other studies of constitutively active
      STAT mutants, provides insight into the pathogenesis and treatment of STAT5
      driven cancer.

PMID- 29199996
TI  - Antisense oligonucleotides offer hope to patients with Charcot-Marie-Tooth
      disease type 1A.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common heritable
      peripheral neuropathy and results from a duplication on chromosome 17 that
      results in an extra copy and increased dosage of peripheral myelin protein 22
      (PMP22). Zhao et al., in this issue of the JCI, successfully utilized antisense
      oligonucleotides (ASOs) to reduce PMP22 and ameliorated neuropathy in both mouse
      and rat models of CMT1A. These data confirm that strategies to reduce PMP22 have
      potential as effective therapeutic approaches for CMT1A and lay the groundwork
      for clinical trials in humans afflicted with this chronic, debilitating
      neurodegenerative disease.

PMID- 29199997
TI  - Thrombolysis for Acute Ischemic Stroke After Protamine Reversal of Heparin.

PMID- 29199998
TI  - Machine Learning for Fetal Growth Prediction.
AB  - Birthweight is often used as a proxy for fetal weight. Problems with this
      practice have recently been brought to light. We explore whether data available
      at birth can be used to predict estimated fetal weight using linear and quantile
      regression, random forests, Bayesian additive regression trees, and generalized
      boosted models. We train and validate each approach using 18,517 pregnancies
      (31,948 ultrasound visits) from the Magee-Womens Obstetric Maternal and Infant
      data and 240 pregnancies in a separate dataset of high-risk pregnancies. We also
      quantify the relation between smoking and small-for-gestational-age birth,
      defined as a birthweight in the lower 10th percentile of a population birthweight
      standard and estimated and predicted fetal weight standard. Using mean squared
      error and median absolute deviation criteria, quantile regression performed best
      among the regression-based approaches, but generalized boosted models performed
      best overall. Using the birthweight standard, smoking during pregnancy increased
      the risk of small-for-gestational-age 3.84-fold (95% CI: 2.70, 5.47). This ratio
      dropped to 1.65 (95% CI: 1.50, 1.81) when using the correct fetal weight
      standard, which was no different from the machine learning-based predicted
      standards, but higher than the regression-based predicted standards. Machine
      learning algorithms show promise in recovering missing fetal weight information.
      See video abstract at, http://links.lww.com/EDE/B314.

PMID- 29199999
TI  - Effect of Inhalation Aromatherapy on Procedural Pain and Anxiety After Needle
      Insertion Into an Implantable Central Venous Port Catheter: A Quasi-Randomized
      Controlled Pilot Study.
AB  - BACKGROUND: Needle insertion into an implantable central venous port catheter may
      lead to procedural pain and anxiety in cancer patients. OBJECTIVE: The aim of
      this study was to determine the effects of inhalation aromatherapy on procedural
      pain and anxiety after needle insertion into an implantable central venous port
      catheter. METHODS: This study included 123 cancer patients who were scheduled to
      undergo chemotherapy. Patients were randomly assigned to either the lavender
      group (n = 41), the eucalyptus group (n = 41), or a control group (n = 41).
      Participants in the intervention groups inhaled 3 drops of essential oil for 3
      minutes before needle insertion into an implantable venous port catheter.
      Patients in the control group received no intervention before needle insertion.
      Data were collected using the visual analog scale (VAS) and State Anxiety
      Inventory. RESULTS: The average VAS scores of the lavender group were
      significantly lower than those of the control group (P < .05). There were no
      significant differences in the average VAS scores between the eucalyptus group
      and the control group (P > .05). In addition, the average State Anxiety Inventory
      scores of the lavender group, the eucalyptus group, and the control group were
      not significantly different (P > .05). CONCLUSION: Inhalation aromatherapy with
      lavender may be an effective technique to relieve pain related to needle
      insertion into an implantable central venous port catheter. IMPLICATIONS FOR
      PRACTICE: Inhalation aromatherapy with lavender oil may be useful in the
      management of procedural pain levels during needle procedure. However, further
      randomized controlled trials are needed to validate this study.

PMID- 29200000
TI  - Mutual Support and Challenges Among Chinese Couples Living With Colorectal
      Cancer: A Qualitative Study.
AB  - BACKGROUND: A diagnosis of cancer and its treatment affect couples as a unit, and
      they must cope and give each other mutual support as dyads. Few studies have
      focused explicitly on understanding mutual support among couples coping with
      colorectal cancer (CRC). OBJECTIVE: The aim of this study was to explore the
      mutual support of couples in their journey of coping together with CRC. METHODS:
      This is a qualitative descriptive study with purposeful sampling. A total of 11
      couples in which 1 partner has been diagnosed with CRC were recruited for in
      depth interviews. RESULTS: Three themes and 8 subthemes emerged from a
      conventional content analysis. The 3 themes were mutual support and reciprocity,
      challenges confronted in the provision of support, and experiencing
      adjustments/outcomes. CONCLUSION: The findings of this study provide insights to
      healthcare professionals on the process by which couples coping with CRC give
      each other mutual support and the related challenges. This will aid in the
      development of an intervention program to support such couples, through enhancing
      their mutual support, overcoming challenges, and improving their
      adjustment/outcomes. IMPLICATIONS FOR PRACTICE: Healthcare professionals need to
      (1) include the spouse of the cancer patients in their care and provide them with
      support, (2) encourage the couples to share their concerns with each other, (3)
      encourage spousal caregivers to take good care of themselves while providing
      support to their loved ones with CRC, and (4) develop a couple-based intervention
      program in providing support to couples coping with cancer as dyads.

PMID- 29200001
TI  - Effect of Aromatherapy Massage on Chemotherapy-Induced Peripheral Neuropathic
      Pain and Fatigue in Patients Receiving Oxaliplatin: An Open Label Quasi
      Randomized Controlled Pilot Study.
AB  - BACKGROUND: Patients receiving oxaliplatin may experience peripheral neuropathic
      pain and fatigue. Aromatherapy massage, a nonpharmacological method, may help to
      control these symptoms. OBJECTIVE: The aim of this open-label, parallel-group,
      quasi-randomized controlled pilot study was to investigate the effect of
      aromatherapy massage on chemotherapy-induced peripheral neuropathic pain and
      fatigue in patients receiving oxaliplatin. METHODS: Stratified randomization was
      used to allocate 46 patients to 2 groups: intervention (n = 22) and control (n =
      24). Between week 1 and week 6, participants in the intervention group (IG)
      received aromatherapy massage 3 times a week. There was no intervention in weeks
      7 and 8. The control group (CG) received routine care. Neuropathic pain was
      identified using the Douleur Neuropathique 4 Questions; severity of painful
      paresthesia was assessed with the numerical rating scale; fatigue severity was
      identified with the Piper Fatigue Scale. RESULTS: At week 6, the rate of
      neuropathic pain was significantly lower in the IG, when compared with the CG.
      The severity of painful paresthesia based on numerical rating scale in the IG was
      significantly lower than that in the CG at weeks 2, 4, and 6. At week 8, fatigue
      severity in the IG was significantly lower when compared with CG (P < .05).
      CONCLUSION: Aromatherapy massage may be useful in the management of chemotherapy
      induced peripheral neuropathic pain and fatigue. IMPLICATIONS FOR PRACTICE: This
      pilot study suggests that aromatherapy massage may be useful to relieve
      neuropathic pain and fatigue. However, there is a need for further clinical
      trials to validate the results of this study.

PMID- 29200002
TI  - Metformin and melatonin inhibit DMBA-induced mammary tumorigenesis in rats fed a
      high-fat diet.
AB  - The data from in-vitro and in-vivo studies show that both peroral antidiabetic
      metformin (MF) and pineal hormone melatonin (MT) inhibit the growth of many
      cancers, including breast cancer. However, most in-vivo studies used standard
      type diet with low fat content. Therefore, in this study, we evaluated the
      chemopreventive effect of MF and MT in an in-vivo model of breast cancer in rats
      on a high-fat diet (10% of total fat). Mammary carcinogenesis was induced by 7,12
      dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats. Chemoprevention
      with MF (administered in a diet, 0.2%) and MT (administered in tap water, 20
      mg/l) was induced 20 days before the carcinogen administration through the
      termination of the experiment (14 weeks after carcinogen administration). Tumor
      growth parameters were analyzed together with histopathological examination and
      immunohistochemical detection of KI67 (proliferation marker), caspase-3, BAX, BCL
      2 (apoptosis markers), and CD24 and CD44 (cancer stem cell markers) in mammary
      tumor samples. The combination of chemopreventive agents decreased tumor
      incidence by 29%. Cumulative tumor volume was lower in all groups treated with
      chemoprevention. Histopathology did not show significant changes in high
      grade/low-grade tumor ratio. Immunohistochemistry showed increased expression of
      BAX in the MT group, and caspase-3 expression increased in both MT and
      combination groups. MT, and particularly the MF and MT combination, inhibited
      DMBA-induced mammary tumor growth in rats by apoptosis stimulation in cancer
      cells. Our results indicate that MT supplements in patients treated with MF may
      have a considerable effect on the incidence of breast cancer.

PMID- 29200003
TI  - Effects of the antidepressants desipramine and fluvoxamine on latency to
      immobility and duration of immobility in the forced swim test in adult male
      C57BL/6J mice.
AB  - The forced swim test in rodents allows rapid detection of substances with
      antidepressant-like activity, evidenced as a decreased duration of immobility
      that is produced by the majority of clinically used antidepressants.
      Antidepressants also increase the latency to immobility, and this additional
      measure reportedly can increase the sensitivity of the forced swim test in mice.
      Extending these findings, the present study examined the effects of desipramine
      and fluvoxamine in a forced swim test in C57BL/6J mice, a strain commonly used as
      background for genetic modifications, analyzing results with a method (i.e.
      survival analysis) that can model the skewed distribution of latencies and that
      can deal with censored data (i.e. when immobility does not occur during the
      test), in comparison with the more traditional Student's t-test. Desipramine
      increased the latency to immobility at 32 mg/kg, but not at lower doses.
      Fluvoxamine also did not affect latency at lower doses, but in contrast to
      desipramine, fluvoxamine decreased the latency to immobility at the highest dose
      (i.e. 32 mg/kg). At doses affecting latency to immobility, neither desipramine
      nor fluvoxamine significantly affected duration of immobility. Together, these
      results are generally consistent with the suggestion that inclusion of the
      latency measure can increase the sensitivity of the forced swim test to detect
      antidepressant-like effects in mice.

PMID- 29200005
TI  - In Response to the October 2017 Commentary.

PMID- 29200004
TI  - Effects of a Short Drilling Implant Protocol on Osteotomy Site Temperature and
      Drill Torque.
AB  - PURPOSE: To establish a protocol for reducing the drilling sequence during
      implant site preparation based on temperature and insertion torque. The
      traditional conventional drilling sequence (used several drills with 0.6-mm
      increment each time) was compared with the proposed short drilling protocol (only
      used 2 drills: initial and final drill). MATERIALS AND METHODS: One hundred
      drilling osteotomies were performed in bovine and porcine bones. Sets of 2
      osteotomy sites were created in 5 bone densities using 2 types of drilling
      protocols. Thermographic pictures were captured throughout all drilling
      procedures and analyzed using ThermaCAM Researcher Professional 2.10. Torque
      values were determined during drilling by measuring electrical input and drill
      speed. RESULTS: There were statistically significant differences in bone
      temperature between the conventional and short drilling protocols during implant
      site preparation (analysis of variance P = 0.0008). However, there were no
      significant differences between the 2 types of drilling protocols for both
      implant diameters. Implant site preparation time was significantly reduced when
      using the short drilling protocol compared with the conventional drilling
      protocol (P < 0.001). CONCLUSIONS: Within the limitations of the study, the short
      drilling protocol proposed herein may represent a safe approach for implant site
      preparation.

PMID- 29200006
TI  - Impact of sustained virologic response on short-term clinical outcomes in
      hepatitis C-related cirrhosis.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a common cause of cirrhosis, leading to
      increased morbidity and mortality. Treatment of the underlying etiology has been
      shown to improve fibrosis and cirrhosis. AIM: We sought to evaluate the impact of
      a sustained virologic response on liver chemistries, model for end stage liver
      disease (MELD) score, Child-Pugh-Turcotte score (CPT), and fibrosis 4 score
      (FIB4) in patients with liver cirrhosis secondary to HCV with portal
      hypertension, with or without decompensation. METHODS: Patients with HCV seen in
      our transplant clinic between June 2013 and September 2015 were identified using
      ICD-9 code 573.3. Charts were reviewed retrospectively. RESULTS: We collected
      data from 92 patients with a mean pretreatment MELD score of 9.16+/-2.98. The
      most common genotype was Ia, n=79 (86%). The mean duration of follow-up was
      7.52+/-2.25 months. Transaminitis improved significantly at follow-up versus
      pretreatment [mean aspartate transaminase from 81.2+/-62.9 to 32.4+/-12.0
      (P<0.0001); alanine transaminase 74.7+/-77.8 to 27.7+/-19.4 (P<0.0001)]. Albumin,
      bilirubin, and alpha-fetoprotein improved significantly. MELD scores improved in
      patients with pretreatment scores greater than 10 (P<0.0003), but not in patients
      with pretreatment scores less than 10 (P=0.501). The CPT score decreased from
      6.1+/-0.9 to 5.8+/-0.9 (P<0.0024). The FIB4 score improved significantly in
      patients with baseline FIB4 more than 3.24, but not with higher baseline FIB4.
      CONCLUSION: Use of direct antivirals in patients with decompensated cirrhosis
      because of HCV leads to improved MELD, FIB4, and CPT scores.

PMID- 29200008
TI  - Four Types of Pulse Oximeters Accurately Detect Hypoxia during Low Perfusion and
      Motion.
AB  - BACKGROUND: Pulse oximeter performance is degraded by motion artifacts and low
      perfusion. Manufacturers developed algorithms to improve instrument performance
      during these challenges. There have been no independent comparisons of these
      devices. METHODS: We evaluated the performance of four pulse oximeters (Masimo
      Radical-7, USA; Nihon Kohden OxyPal Neo, Japan; Nellcor N-600, USA; and Philips
      Intellivue MP5, USA) in 10 healthy adult volunteers. Three motions were
      evaluated: tapping, pseudorandom, and volunteer-generated rubbing, adjusted to
      produce photoplethsmogram disturbance similar to arterial pulsation amplitude.
      During motion, inspired gases were adjusted to achieve stable target plateaus of
      arterial oxygen saturation (SaO2) at 75%, 88%, and 100%. Pulse oximeter readings
      were compared with simultaneous arterial blood samples to calculate bias (oxygen
      saturation measured by pulse oximetry [SpO2] - SaO2), mean, SD, 95% limits of
      agreement, and root mean square error. Receiver operating characteristic curves
      were determined to detect mild (SaO2 < 90%) and severe (SaO2 < 80%) hypoxemia.
      RESULTS: Pulse oximeter readings corresponding to 190 blood samples were
      analyzed. All oximeters detected hypoxia but motion and low perfusion degraded
      performance. Three of four oximeters (Masimo, Nellcor, and Philips) had root mean
      square error greater than 3% for SaO2 70 to 100% during any motion, compared to a
      root mean square error of 1.8% for the stationary control. A low perfusion index
      increased error. CONCLUSIONS: All oximeters detected hypoxemia during motion and
      low-perfusion conditions, but motion impaired performance at all ranges, with
      less accuracy at lower SaO2. Lower perfusion degraded performance in all but the
      Nihon Kohden instrument. We conclude that different types of pulse oximeters can
      be similarly effective in preserving sensitivity to clinically relevant hypoxia.

PMID- 29200007
TI  - Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver
      failure.
AB  - Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated
      by acute decompensation of cirrhosis. Recent studies have highlighted the
      importance of the gut-liver axis (GLS) and its association with ACLF
      pathogenesis. In this review, we discuss the mechanisms related to the alteration
      of the GLA and their involvement in ACLF pathogenesis and suggest some possible
      therapeutic options that could modulate the GLA dysfunction. This knowledge may
      provide information useful for the design of therapeutic strategies for gut
      dysbiosis and its complications in ACLF.

PMID- 29200009
TI  - Antifibrinolytic Therapy and Perioperative Considerations.
AB  - Fibrinolysis is a physiologic component of hemostasis that functions to limit
      clot formation. However, after trauma or surgery, excessive fibrinolysis may
      contribute to coagulopathy, bleeding, and inflammatory responses.
      Antifibrinolytic agents are increasingly used to reduce bleeding, allogeneic
      blood administration, and adverse clinical outcomes. Tranexamic acid is the agent
      most extensively studied and used in most countries. This review will explore the
      role of fibrinolysis as a pathologic mechanism, review the different
      pharmacologic agents used to inhibit fibrinolysis, and focus on the role of
      tranexamic acid as a therapeutic agent to reduce bleeding in patients after
      surgery and trauma.

PMID- 29200010
TI  - Role of Systematic Lymphadenectomy to Tailor Adjuvant Therapy in Early
      Endometrial Cancer.
AB  - OBJECTIVE: The long-standing protocol at our center for apparent stage I and II
      endometrial cancers comprises hysterectomy and bilateral salpingo-oophorectomy
      without lymphadenectomy. Adjuvant treatment is based in line with Postoperative
      Radiation Therapy in Endometrial Carcinoma 1 protocol. Our aim was to quantify
      the number of patients who would avoid external beam radiation therapy (EBRT) in
      our institution if we adopted a protocol of lymphadenectomy to tailor adjuvant
      EBRT and its impact on cost and quality of life. DESIGN: Retrospective case
      cohort study. SETTING: Gynecological oncology center. METHODS: All endometrial
      cancers treated from 2007 to 2012 were included. The European Organization for
      Research and Treatment of Cancer (EORTC) quality of life (QLQ-30) and endometrial
      cancer specific (EN-24) questionnaires were used to measure the quality of life.
      The NHS tariff for EBRT, VBT and lymphadenectomy were obtained from our Trust's
      contract with the local commissioning groups. MAIN OUTCOME MEASURES: Quality of
      life and cost. RESULTS: Systematic pelvic lymphadenectomy in early endometrial
      cancers of all grades would avoid EBRT in 23.3% of patients, and if performed for
      grade 2 and 3 cancers, 39.5% of patients would avoid EBRT. The global health
      scores were significantly lower, and pain scores were considerably higher in
      patients who received EBRT. Performing systematic lymphadenectomy and tailored
      adjuvant therapy in grade 2 and 3 endometrial cancers would save L134,691 and for
      all grades save L37,161 for every 100 patients treated with early endometrial
      cancer. CONCLUSION: Systematic lymphadenectomy with tailored adjuvant therapy may
      offer better QoL with reduced cost to NHS without a reduction in overall
      survival.

PMID- 29200011
TI  - Coronal CT is Comparable to MR Imaging in Aiding Diagnosis of Dementia in a
      Memory Clinic in Singapore.
AB  - PURPOSE: The present study investigated (a) the agreement between computerized
      tomography (CT) and 3 T magnetic resonance imaging (MRI) in the visual grading of
      medial temporal atrophy (MTA); and (b) whether MTA on CT differentiated patients
      with dementia from no dementia in memory clinics. MATERIALS AND METHODS: Data
      were obtained from patients who underwent CT scans at the National University
      Hospital of Singapore, and from a subsample who subsequently underwent 3 T MRI
      scans in a research study. Agreements and disagreements between CT and MRI were
      determined. Area under the curve (AUC) analyses determined if CT-graded MTA
      distinguished patients with dementia from no dementia. RESULTS: Of the 107
      patients in the subsample, MTA scores of 71 agreed on both CT and MRI. The true
      positive rate between CT and MRI for MTA scores >=2 was 79.7%. The true negative
      rate for MTA scores between 0 and 1 was 96.4%. CT underestimated MTA severity in
      33 of 36 disagreements with the MRI. MTA scores >=2 on CT distinguished dementia
      from no dementia in both discovery [n=263; AUC (95% confidence interval)=0.77
      (0.72-0.83); sensitivity=0.69; specificity=0.74] and validation [n=264; AUC (95%
      confidence interval)=0.77 (0.71-0.82); sensitivity=0.72; specificity=0.72]
      groups. CONCLUSIONS: MTA graded on CT is a viable alternative to MRI to aid in
      the diagnosis of dementia in memory clinics.

PMID- 29200012
TI  - A Naturalistic Evaluation of Change in Antidepressant Prescription in Patients
      With Affective and Anxiety Disorders in a Tertiary Care Hospital of India.
AB  - BACKGROUND: Although many studies have evaluated prescription patterns, there is
      lack of information on the choice of antidepressants among patients who do not
      respond antidepressants. Similarly, information on switching strategies is also
      limited. This naturalistic study aimed to evaluate the switching strategies and
      preferred antidepressants by the psychiatrists among patients who do not respond
      to or who are not able to tolerate an antidepressant. METHODS: A cross-sectional
      observational study design was followed. Patients diagnosed with affective and
      anxiety disorders, who were recommended a change in antidepressant, were
      recruited. Details of antidepressant before switching, antidepressants considered
      at the time of switching, coprescription advised at the time of switching,
      reasons considered for switching, and strategy advised at the time of switching
      were noted down. RESULTS: A total of 102 patients were recruited. The most common
      change strategy was selective serotonin reuptake inhibitor (SSRI) to a serotonin
      norepinephrine reuptake inhibitor (SNRI) (N = 42; 41.17%), and this was followed
      by SSRI to SSRI (N = 18; 17.64%) and SNRI to SSRI (N = 10; 9.8%). In majority of
      the patients (N = 79; 77.45%) cross-taper of older antidepressant with gradual
      increase in dose of newer antidepressants was followed. About 44.1% of the
      patients were on adjuvant medications at the time of considering change in
      antidepressants, and 37.25% of the patients were additionally started on some
      adjuvant medications during the change of antidepressants. CONCLUSIONS: The
      present study suggests that the most common strategy followed during change of
      antidepressant is from SSRI to SNRI and this is followed by SSRI to SSRI and SNRI
      to SSRI. Cross-taper switching strategy along with the use of adjuvant
      medications like benzodiazepines during the process of switching is most commonly
      followed.

PMID- 29200013
TI  - Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic
      Brain: Relationship Between Density and Direct Volumetry.
AB  - OBJECTIVES: Net water uptake per volume of brain tissue may be calculated by
      computed tomography (CT) density, and this imaging biomarker has recently been
      investigated as a predictor of lesion age in acute stroke. However, the
      hypothesis that measurements of CT density may be used to quantify net water
      uptake per volume of infarct lesion has not been validated by direct volumetric
      measurements so far. The purpose of this study was to (1) develop a theoretical
      relationship between CT density reduction and net water uptake per volume of
      ischemic lesions and (2) confirm this relationship by quantitative in vitro and
      in vivo CT image analysis using direct volumetric measurements. MATERIALS AND
      METHODS: We developed a theoretical rationale for a linear relationship between
      net water uptake per volume of ischemic lesions and CT attenuation. The derived
      relationship between water uptake and CT density was tested in vitro in a set of
      increasingly diluted iodine solutions with successive CT measurements.
      Furthermore, the consistency of this relationship was evaluated using human in
      vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct
      lesions, net water uptake was determined by direct measurement of the volumetric
      difference between the ischemic and normal hemisphere and was correlated with net
      water uptake calculated by ischemic density measurements. RESULTS: With regard to
      in vitro data, water uptake by density measurement was equivalent to direct
      volumetric measurement (r = 0.99, P < 0.0001; mean +/- SD difference, -0.29% +/-
      0.39%, not different from 0, P < 0.0001). In the study cohort, the mean +/- SD
      uptake of water within infarct measured by volumetry was 44.7 +/- 26.8 mL and the
      mean percent water uptake per lesion volume was 22.7% +/- 7.4%. This was
      equivalent to percent water uptake obtained from density measurements: 21.4% +/-
      6.4%. The mean difference between percent water uptake by direct volumetry and
      percent water uptake by CT density was -1.79% +/- 3.40%, which was not
      significantly different from 0 (P < 0.0001). CONCLUSIONS: Volume of water uptake
      in infarct lesions can be calculated quantitatively by relative CT density
      measurements. Voxel-wise imaging of water uptake depicts lesion pathophysiology
      and could serve as a quantitative imaging biomarker of acute infarct lesions.

PMID- 29200014
TI  - Increased Delay Between Gadolinium Chelate Administration and T1-Weighted
      Magnetic Resonance Imaging Acquisition Increases Contrast-Enhancing Tumor Volumes
      and T1 Intensities in Brain Tumor Patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of delayed T1
      weighted (T1-w) MRI acquisition after gadolinium chelate administration on brain
      tumor volumes and T1-w intensities. MATERIALS AND METHODS: Fifty-five patients
      with histologically confirmed, contrast-enhancing intra-axial brain tumors were
      analyzed in this prospective test-retest study. Patients underwent 2 consecutive
      3 T MRI scans (separated by a 1-minute break) during routine follow-up with
      contrast-enhanced T1 (ceT1-w), T2, and FLAIR acquisition. Macrocyclic gadolinium
      chelate-based contrast agent was only administered before the first ceT1-w
      acquisition; median latency to ceT1-w acquisition was 6.72 minutes (IQR, 6.53
      6.92) in the first and 16.27 minutes (IQR, 15.49-17.26) in the second scan.
      Changes in tumor volumes and relative ceT1-w intensities between the 2
      acquisitions were quantitatively assessed following semiautomated tumor
      segmentation (separately for contrast-enhancement [CE], necrosis [NEC], and
      nonenhancing [NE] tumor). RESULTS: Semiautomatically segmented CE tumor volumes
      were significantly larger in the second acquisition (median +32% [1.2 cm]; IQR,
      16%-62%; P < 0.01), which corresponded to a 10% increase in CE tumor diameter
      (+0.3 cm). Contrarily, NEC and NE tumor volumes were significantly smaller
      (median -24% [IQR, -36% to -54%], P < 0.01 for NEC and -2% [IQR, -1% to -3%], P =
      0.02 for NE tumor). Bland-Altman plots confirmed a proportional bias toward
      higher CE and lower NEC volumes for the second ceT1-w acquisition. Relative ceT1
      w intensities for both early- (regions already enhancing in the first scan) and
      late-enhancing (newly enhancing regions in the second scan) tumor were
      significantly increased in the second acquisition (by 5.8% and 27.3% [P < 0.01,
      respectively]). Linear-mixed effects modeling confirmed that the increase in CE
      volumes and CE intensities is a function of the interval between contrast agent
      injection and ceT1-w acquisition (P < 0.01 each). CONCLUSIONS: Our study
      indicates that the maximum extent of CE tumor volumes and intensities may
      increase beyond the time frame of 4 to 8 minutes after contrast agent injection
      and potentially affects the diagnosis of progressive or recurrent disease because
      late-enhancing recurrent disease might not be unequivocally detected on standard
      follow-up MRI.

PMID- 29200015
TI  - Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With
      Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical
      Trial.
AB  - BACKGROUND: The involvement of inflammatory components in the pathophysiology of
      low back pain (LBP) is poorly understood. It has been suggested that spinal
      manipulative therapy (SMT) may exert anti-inflammatory effects. PURPOSE: The
      purpose of this study was to determine the involvement of inflammation-associated
      chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the
      effect of SMT on that process. METHODS: Patients presenting with nonradicular,
      nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were
      recruited according to stringent inclusion criteria. They were evaluated for
      appropriateness to treat using a high velocity low amplitude manipulative thrust
      in the lumbar-lumbosacral region. Blood samples were obtained at baseline and
      following the administration of a series of 6 high velocity low amplitude
      manipulative thrusts on alternate days over the period of 2 weeks. The in vitro
      levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma
      levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were
      determined at baseline and at the termination of treatments 2 weeks later.
      RESULTS: Compared with asymptomatic controls baseline production of all
      chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of
      CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production
      was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE
      selectin levels were significantly higher (P=0.003) in chronic but not in acute
      LBP patients. Following SMT, patient-reported outcomes showed significant
      (P<0.0001) improvements in visual analog scale and Oswestry Disability Index
      scores. This was accompanied by a significant decline in CCL3 production
      (P<0.0001) in both groups of patients. Change scores for CCL4 production differed
      significantly (P<0.0001) only for the acute LBP cohort, and no effect on the
      production of CCL2 or plasma sE-selectin levels was noted in either group.
      CONCLUSIONS: The production of chemotactic cytokines is significantly and
      protractedly elevated in LBP patients. Changes in chemokine production levels,
      which might be related to SMT, differ in the acute and chronic LBP patient
      cohorts.

PMID- 29200017
TI  - Efficacy of 8 Different Drug Treatments for Patients With Trigeminal Neuralgia: A
      Network Meta-analysis.
AB  - OBJECTIVES: Trigeminal neuralgia (TN) is commonly seen in older persons and
      negatively influences their daily life. Although some research on the efficacy of
      TN drugs has been conducted, the optimal choice still remains uncertain.
      Therefore, this network meta-analysis (NMA) evaluated the efficacy and
      performance of 8 drugs with respect to TN. METHODS: All literature was retrieved
      from the PubMed and Embase electronic databases by jointly searching key terms.
      The only outcome was response rate, expressed as the odds ratio with 95%
      credible/confidence intervals. Both a pairwise meta-analysis and NMA were
      conducted. Heat plot and node splitting were computed to measure the consistency
      between direct and indirect evidence. In addition, surface under cumulative
      ranking curves were utilized to rank different drugs for treating TN. RESULTS: In
      total, 13 studies and 672 TN patients were included in this NMA. With regard to
      the primary endpoint response rate, only lidocaine (LDC), botulinum toxin type A
      (BTX-A), and carbamazepine (CBZ) had a statistical better performance than the
      placebo. According to the surface under cumulative ranking curves, LDC, BTX-A,
      and CBZ are the most effective drugs for treating patients with TN. CONCLUSIONS:
      Among the 8 drugs investigated, all exhibited a capacity to alleviate TN more
      than the placebo except for pimozide and proparacaine. Moreover, LDC, BTX-A, and
      CBZ stood out for their high efficacy and could be recommended as the primary
      choice of treatment for TN.

PMID- 29200016
TI  - Intravenous Acetaminophen Reduces Length of Stay Via Mediation of Postoperative
      Opioid Consumption After Posterior Spinal Fusion in a Pediatric Cohort.
AB  - OBJECTIVES: Since approval of intravenous acetaminophen (IV APAP), its use has
      become quite common without strong positive evidence. Our goal was to determine
      the effect of IV APAP on length of hospital stay (LOS) via mediation of opioid
      related side effects in pediatric patients. MATERIALS AND METHODS: After
      Institutional Review Board approval, 114 adolescents undergoing posterior spinal
      fusion were prospectively recruited and managed postoperatively with patient
      controlled analgesia and adjuvant therapy. Patients were divided into 2 groups
      based on the use of IV APAP: control (n=70) and treatment (n=44). Association of
      IV APAP use with opioid outcomes was analyzed using inverse probability of
      treatment weighting (IPTW)-adjusted propensity scores to balance the 2 groups for
      all significant covariates except postoperative opioid consumption. Mediation
      analysis was carried out for LOS with IV APAP as the independent variable and
      morphine consumption as the mediator. RESULTS: Oral intake was delayed by ~1 day
      (P<0.001) and LOS was 0.6 days longer in the control group (P=0.044). After IPTW,
      time to oral intake remained significantly longer in the control group (P=0.014).
      The mediation model with IPTW revealed a significant negative association between
      IV APAP and morphine consumption (P<0.001), which significantly increased LOS
      (P<0.003). IV APAP had a significant opioid-sparing effect associated with
      shorter LOS. DISCUSSION: IV APAP hastens oral intake and is associated with
      decreased LOS in an adolescent surgery population likely through decreased opioid
      consumption. Through addition of IV APAP in this population, LOS may be
      decreased, an important implication in the setting of escalating health care
      costs.

PMID- 29200018
TI  - The Diagnostic and Prognostic Role of Interleukin 12B and Interleukin 6R Gene
      Polymorphism in Patients With Ankylosing Spondylitis.
AB  - OBJECTIVES: Interleukin 23 (IL-23) pathway and IL-1 cluster genes play prominent
      role in the etiopathology of ankylosing spondylitis (AS). The aim of this study
      was to investigate the diagnostic and prognostic role of 5 single-nucleotide
      polymorphisms related to IL-23 pathway and IL-1 cluster genes in AS patients.
      METHODS: Four hundred thirty-one patients with AS and 206 age- and sex-matched
      healthy controls were recruited in this prospective cohort study. Five potential
      single-nucleotide polymorphisms (IL-23R [rs11209026], IL-12B [rs6871626], TYK2
      [rs6511701], IL-6R [rs4129267], and IL-1R2 [rs2192752]) related to IL-23 pathway
      and IL-1 cluster genes by analyzing previous studies were genotyped. Among 431
      total AS patients, 198 active cases were treated and followed up for 24 weeks.
      RESULTS: Frequencies of IL-12B AA (rs6871626) and IL-6R TT (rs4129267) genotypes
      were increased in AS patients compared with healthy controls (both P < 0.001),
      and IL-12B A (rs6871626) as well as IL-6R T (rs4129267) allele increased the risk
      of AS independently (both P < 0.001). The Bath Ankylosing Spondylitis Disease
      Activity Index score was found to be elevated in AS patients with IL-12B AA
      (rs6871626) compared with patients with the CA and CC genotypes (P = 0.002 and P
      < 0.001, respectively), and the Bath Ankylosing Spondylitis Functional Index
      score was also increased in AS patents with IL-12B AA (rs6871626) than in those
      with the CA and CC genotypes (P = 0.001 and P < 0.001). In addition, IL-6R T
      (rs4129267) allele could predict a worse ASAS-20 (Assessment of SpondyloArthritis
      international Society) response at week 24 as an independent factor by
      multivariate logistic regression analysis with additive model (P = 0.011).
      CONCLUSIONS: Interleukin 12B (rs6871626) and IL-6R (rs4129267) gene polymorphisms
      could serve as promising biomarkers for diagnosis and prognosis in AS patients.

PMID- 29200019
TI  - The Impact of Intra-articular Depot Betamethasone Injection on Insulin Resistance
      Among Diabetic Patients With Osteoarthritis of the Knee: A Case-Control Study.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of intra-articular
      corticosteroid injection (IACI) of depot betamethasone at the knee joint on
      insulin resistance (IR). METHODS: Patients with type 2 diabetes, non-insulin
      treated, with painful osteoarthritis of the knee were requested to participate in
      our study. After consent, demographic, clinical, and laboratory parameters were
      documented in addition to fasting blood glucose (FBG) and fasting blood insulin
      levels just prior to IACI of 1 mL of depot betamethasone. Fasting blood glucose
      and fasting blood insulin levels were repeated the next day following the IACI
      and 8 days later. Age- and sex-matched group of patients with type 2 diabetes
      from the same clinic were recruited as a control group (case-control study).
      Insulin resistance was calculated using Homeostasis Model Assessment-Insulin
      Resistance. Mann-Whitney U test, chi test, and Wilcoxon signed rank tests were
      used for statistical analysis. RESULTS: Eleven patients were recruited in the
      patients' group and 10 patients in the control group. Median FBG in the patients'
      group at baseline was 148 +/- 51 mg/dL, and median IR was 5.12 +/- 2.46. One day
      following the IACI, median FBG level was 247 +/- 104 mg/dL (P = 0.004, compared
      with baseline), with median IR of 20.8 +/- 7.01 (P = 0.0039). The median ratios
      of blood glucose and IR 1 day following the IACI compared with baseline were 1.7
      and 4.1, respectively. Eight days following the IACI, mean FBG and IR levels were
      not significantly different from baseline. CONCLUSIONS: Intra-articular
      corticosteroid injection of betamethasone at the knee joint among patients with
      diabetes was associated with a significant increase in IR levels compared with
      baseline levels, 1 day following the injection. The mean percentage of increase
      in IR was higher than that for FBG levels.

PMID- 29200020
TI  - Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing
      Rheumatoid Arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies
      to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with
      long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA
      patients and 16 age- and sex-matched control subjects participated in this cross
      sectional study. All underwent complete lung function tests and provided induced
      sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine
      containing (NorP) peptides in the sputum of the RA patients and control subjects,
      as well as in the serum of the RA patients, were determined by enzyme-linked
      immunosorbent assay. RESULTS: Patients with RA had the following characteristics:
      mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44,
      and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high
      titers of ACPAs in their sera. Four of the seropositive (40%), none of the
      seronegative RA patients, and only 1 of the control subjects showed detectable
      levels of ACPAs in their sputum. The ratio between the reactivity with CitP and
      NorP peptides in the sputum was significantly higher in RA sputum than in control
      sputum (1.33 +/- 1.2 vs. 0.64 +/- 0.14, P = 0.02). A positive correlation was
      found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti
      CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in
      the sputum. No significant correlation was found between sputum ACPAs and disease
      severity, history of smoking, lung function tests, or treatment for RA.
      CONCLUSIONS: Anticitrullinated protein/peptide antibodies can be detected in the
      sputum of RA patients and are correlated with the presence in the serum.

PMID- 29200021
TI  - Sonographic Findings of Hands and Wrists in Systemic Lupus Erythematosus Patients
      With Jaccoud Arthropathy.
AB  - INTRODUCTION: Jaccoud arthropathy (JA) is a deforming nonerosive arthropathy,
      characterized by the presence of "reversible" joint deformity. The study aims at
      describing the main musculoskeletal ultrasound (US) findings of a series of
      systemic lupus erythematosus (SLE) patients with JA. METHODS: Consecutive
      patients diagnosed as having JA and SLE were included in the study. All patients
      underwent a whole clinical evaluation and US of the hands and wrists. The US scan
      evaluated the presence of synovial hypertrophy, tenosynovitis, and bone erosions.
      RESULTS: Thirty-nine of 40 patients were female. The US examination was performed
      on 560 joints of the hands and wrists. At least 1 change was observed in the US
      examination of 20 patients (50.0%), but there was not a statistically significant
      association with disease activity (P = 0.33). Nineteen patients (47.5%) had
      synovial hypertrophy, 9 (22.5%) had tenosynovitis, and 7 (17.5%) had both.
      Isolated small bone erosions were identified in 2 patients (5.0%). CONCLUSIONS:
      Ultrasound examination is a reliable and noninvasive imaging method for the
      evaluation of joint involvement in SLE. Half of the patients with JA have
      ultrasonographic signs of joint inflammation, and these abnormalities may be
      found even in the absence of disease activity.

PMID- 29200022
TI  - Relationship Between Ventricular Arrhythmias, Conduction Disorders, and
      Myocardial Fibrosis in Patients With Systemic Sclerosis.
AB  - BACKGROUND: Delayed-enhancement magnetic resonance imaging (DE-MRI) is a
      noninvasive diagnostic tool able to identify myocardial fibrosis. In patients
      with scleroderma, its relationship with arrhythmias and conduction disorders has
      not been fully explored. OBJECTIVES: The aim of this study was to evaluate the
      possible correlations between ventricular arrhythmias, conduction disorders, and
      myocardial fibrosis in patients with systemic sclerosis. METHODS: Thirty-six
      patients with diffuse or limited cutaneous scleroderma underwent 12-lead
      electrocardiogram (ECG), 24-hour Holter ECG monitoring, transthoracic
      echocardiography, and cardiac DE-MRI, with gadolinium administration in 33
      patients. RESULTS: High-quality DE-MRI scans were obtained in 30 patients.
      Myocardial fibrosis was detected in 25 patients (83.3%). Eighteen patients (60%)
      had ventricular arrhythmias or conduction disorders. There was no significant
      difference in ventricular arrhythmia burden (the total number of premature
      ventricular contractions [PVCs]/24 hours) (48 +/- 304 vs. 69 +/- 236, P = 0.97),
      ventricular arrhythmia severity (couplets, triplets, runs) on Holter ECG, or in
      the presence of conduction disorders (36% vs. 40%, P = 0.86) between patients
      with and without myocardial fibrosis. In univariate analysis, diffuse fibrosis
      was weakly associated with the number of PVCs/24 hours (R = 0.157, P = 0.03). A
      number of at least 597 PVCs/24 hours had a sensitivity of 60% and a specificity
      of 92% in predicting the presence of diffuse fibrosis on DE-MRI (area under the
      curve = 0.640). CONCLUSIONS: Delayed-enhancement magnetic resonance imaging can
      identify myocardial fibrosis in a high percentage of scleroderma patients. Its
      presence does not seem to influence the ventricular arrhythmia burden and
      severity or the presence of conduction disorders, with the exception of diffuse
      myocardial fibrosis, which modestly influences the total number of PVCs/24 hours.

PMID- 29200023
TI  - Large Artery Dysfunction in Primary Antiphospholipid Syndrome.
AB  - OBJECTIVE: The aim of this study was to assess the arterial distensibility of
      large vessels and changes in microvasculature in primary antiphospholipid
      syndrome. METHODS: Twenty-two antiphospholipid syndrome (APL) patients and 66 age
      , sex-, height-, and blood pressure-matched controls were evaluated. Second
      derivative of the finger photoplethysmogram (SDPTG) was used as a noninvasive
      method to evaluate the pulse wave. The b/a and d/a indices, which reflect,
      respectively, large-vessel and small-vessel properties, were calculated from the
      SDPTG waveform components. Vascular age index was also determined. RESULTS:
      Arterial thrombosis occurred in 59.1% (13/22) of APL patients, with a
      predominance of stroke episodes (61.5%). Venous thromboembolism was observed in
      36.4% (all deep venous thrombosis), and obstetric complications in 36.4%.
      Frequency of diabetes mellitus, smoking, and dyslipidemia was comparable in APL
      patients and control subjects (P > 0.05). Concerning plethysmography findings,
      b/a ratio was higher in patients than in control subjects (-0.44 +/- 0.16 vs. 
      0.54 +/- 0.18, P = 0.034), whereas d/a ratio (-0.30 +/- 0.16 vs. -0.31 +/- 0.18,
      P = 0.83) was comparable. Moreover, SDPTG (-0.16 +/- 0.35 vs. -0.30 +/- 0.38, P =
      0.16) and vascular age index values (53.5 +/- 11.6 vs. 51.8 +/- 16.1, P = 0.65)
      were alike in both groups. Regarding disease-related factors, patients with
      arterial and venous thrombosis had similar b/a, d/a, and vascular age indices (P
      = 0.95; P = 0.06; P = 0.12, respectively). CONCLUSIONS: The higher b/a ratio in
      APL patients suggests decreased distensibility of large arteries and may be why
      APL patients are at higher risk for cardiovascular events. The d/a ratio, that is
      considered a marker of small vessel vascular resistance, was not different than
      controls. Further studies are needed to evaluate vascular factors that predispose
      APL patients to atherosclerotic events.

PMID- 29200025
TI  - Granulomatosis With Polyangiitis in a Young Adult With Down Syndrome: Therapeutic
      Challenges and Clues to Immunopathogenesis.

PMID- 29200024
TI  - Granulomatosis With Polyangiitis and Continuous Positive Airway Pressure-The
      Challenge of Interface Between Nose and Mask.

PMID- 29200026
TI  - Severe Aortic Valve Regurgitation in Relapsing Polychondritis.

PMID- 29200027
TI  - Familial Mediterranean Fever Imitating Lupus Flare: A Rare Coexistence of an
      Autoimmune Disease With an Autoinflammatory Disease.

PMID- 29200028
TI  - Proliferative Diffuse Glomerulonephritis in Rheumatoid Arthritis.

PMID- 29200029
TI  - Therapeutic Guidelines for Latin American Lupus Patients: Methodology.

PMID- 29200031
TI  - NACNS Newsletter: President's Message.

PMID- 29200030
TI  - Resveratrol for patients with chronic obstructive pulmonary disease: hype or
      hope?
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a progressive
      lung disease with a high prevalence of extrapulmonary manifestations and,
      frequently, cardiovascular comorbidity. Resveratrol is a food-derived compound
      with anti-inflammatory, antioxidant, metabolic and cardioprotective potential.
      Therefore, resveratrol might improve the pulmonary as well as extrapulmonary
      pathology in COPD. In this review, we will evaluate knowledge on the effects of
      resveratrol on lung injury, muscle metabolism and cardiovascular risk profile and
      discuss if resveratrol is a hype or hope for patients with COPD. RECENT FINDINGS:
      Experimental models of COPD consistently show decreased inflammation and
      oxidative stress in the lungs after resveratrol treatment. These beneficial anti
      inflammatory and antioxidant properties of resveratrol can indirectly also
      improve both skeletal and respiratory muscle impairment in COPD. Recent clinical
      studies in non-COPD populations show improved mitochondrial oxidative metabolism
      after resveratrol treatment, which could be beneficial for both lung and muscle
      impairment in COPD. Moreover, preclinical studies suggest cardioprotective
      effects of resveratrol but results of clinical studies are inconclusive. SUMMARY:
      Resveratrol might be an interesting therapeutic candidate to counteract lung and
      muscle impairments characteristic to COPD. However, there is no convincing
      evidence that resveratrol will significantly decrease the cardiovascular risk in
      patients with COPD.

PMID- 29200032
TI  - Faculty Responsibilities With Publishing Student Work.

PMID- 29200033
TI  - Clinical Nurse Specialist Certification Examinations: Legal and Ethical
      Considerations.

PMID- 29200034
TI  - Research Intervention Fidelity: Tips to Improve Internal Validity of Your
      Intervention Studies.

PMID- 29200035
TI  - Meningococcal Disease: Vaccines-Who's at Risk and the Future.

PMID- 29200036
TI  - Do End-of-Life Care Pathways Improve Outcomes in Caring for the Dying?

PMID- 29200037
TI  - Creating a Research Agenda and Setting Research Priorities for Clinical Nurse
      Specialists.
AB  - PURPOSE/OBJECTIVES: The purpose of this article is to describe the evolution and
      results of the process for establishing a research agenda and identification of
      research priorities for clinical nurse specialists, approved by the National
      Association of Clinical Nurse Specialists (NACNS) membership and sanctioned by
      the NACNS Board of Directors. DESCRIPTION OF THE PROJECT/PROGRAM: Development of
      the research agenda and identification of the priorities were an iterative
      process and involved a review of the literature; input from multiple
      stakeholders, including individuals with expertise in conducting research serving
      as task force members, and NACNS members; and feedback from national board
      members. OUTCOME: A research agenda, which is to provide an enduring research
      platform, was established and research priorities, which are to be applied in the
      immediate future, were identified as a result of this process. CONCLUSION:
      Development of a research agenda and identification of research priorities are a
      key method of fulfilling the mission and goals of NACNS. The process and outcomes
      are described in this article.

PMID- 29200038
TI  - Health Literacy and Health Status in People With Chronic Heart Failure.
AB  - PURPOSE/AIM: The aim of this study was to investigate whether health literacy,
      self-efficacy, and medication adherence can explain or predict the variance in
      health outcomes (measured as perceived physical or mental health status [HS]) in
      persons with chronic heart failure (HF). DESIGN: A nonexperimental cross
      sectional survey study used data gathered from 175 patients with chronic HF from
      urban cardiology practices in the northeast United States. METHODS: The Paasche
      Orlow and Wolf Causal Pathways conceptual model and Bandura's self-efficacy
      theory were used to select and test variables in the study. A demographic
      questionnaire, the Short Test of Functional Health Literacy, the Self-Efficacy
      for Appropriate Medication Use Scale, the Morisky Medication Adherence Scale, and
      the Short Form-12 version 2 assessing perceived physical and mental HS were
      completed. Multiple hierarchical regression analyses were used to analyze
      relationships among the variables. RESULTS: Significant associations between
      health literacy and self-efficacy and between health literacy and perceived
      mental HS were found (P < .05). High self-efficacy was the strongest predictor of
      physical HS (P < .01). The strongest predictor of mental HS was medication
      adherence (P < .01). CONCLUSIONS: Support of self-efficacy and medication
      adherence may improve HS. Including health literacy strategies in clinical
      practice may support improvements in HS in people with chronic HF.

PMID- 29200039
TI  - "It Just Is What It Is": The Positive and Negative Effects of Living With
      Inflammatory Bowel Disease and Irritable Bowel Syndrome.
AB  - PURPOSE: This study aimed to explore the lived experiences of women diagnosed
      with inflammatory bowel disease and/or irritable bowel syndrome enrolled in
      postsecondary education. METHODS: Nine women aged 18 to 26 years participated in
      this study. Data collection consisted of an informed consent form, a background
      questionnaire, and a semistructured one-on-one interview. This interview explored
      the lived experiences of these individuals regarding perceived positive and
      negative effects of living with these conditions. RESULTS: Salient themes that
      emerged from the data were (1) "It can add to my life," (2) "Why me?: My
      condition runs my life," and (3) "I'm doing the best I can with what I have."
      Themes 1 and 2, the themes addressed in this article, were subdivided into (1)
      change in perception of self, condition, and others and (2) healthy lifestyle and
      (1) unpredictability and inconsistencies of inflammatory bowel disease/irritable
      bowel syndrome, (2) lack of understanding, and (3) the inconvenience of
      inflammatory bowel disease/irritable bowel syndrome, respectively. All
      participants expressed both positive and negative effects of living with their
      conditions. CONCLUSION: Community health nurses should be aware of the positive
      and negative effects of living with these conditions to help build relationships
      and assist with condition management. Other implications are discussed.

PMID- 29200041
TI  - Meningococcal Disease: Vaccines-Who's at Risk and the Future.

PMID- 29200040
TI  - The Wisdom of Age.

PMID- 29200042
TI  - At a Tipping Point: Nurses Can Push Narcan to the Mainstream and Save Lives.

PMID- 29200044
TI  - Past Year Substance Use by Student Nurses.
AB  - PURPOSE: Nurses who abuse substances are a threat to patients, colleagues,
      society, and themselves. Research indicates that substance use often begins
      during undergraduate years. The purpose of this research was to identify rates of
      past year substance use by student nurses. METHOD: A quantitative, cross
      sectional, correlational design was used to examine past year substance use by
      student nurses and to determine whether substance use is related to age, gender,
      race, relationship status, ethnicity, country of birth, type of school program,
      and year in program. The convenience sample of National Student Nurses'
      Association members yielded 4,033 completed surveys. Students were asked about
      their past year substance use via Survey Monkey. Responses were analyzed through
      exploratory data analysis and logistic regression. RESULTS: Binge drinking was
      reported by 61% of the student nurses; 18% reported using marijuana; 5% reported
      using illegal drugs, excluding marijuana; 8% reported using nonprescribed
      stimulants to enhance academic performance; and 10% reported using nonprescribed
      prescription pills. Students who were younger than 28 years old, White, male,
      born in this country, or single tended to report more substance misuse than other
      students. CONCLUSIONS: The results suggest that student nurses tend to use fewer
      drugs than their college counterparts but are slightly more likely to binge
      drink. Further research is needed on the effect of substance education in the
      beginning of the nursing program and that continued throughout the program on
      student nurse substance use. Research on faculty's ability to identify the at
      risk student is necessary for early intervention.

PMID- 29200045
TI  - The Addition of Dexmedetomidine as an Adjunctive Therapy to Benzodiazepine Use in
      Alcohol Withdrawal Syndrome: A Literature Review.
AB  - Alcohol withdrawal syndrome (AWS) is commonly encountered in the intensive care
      unit population. Currently, the mainstay treatment for AWS is the use of
      benzodiazepines. However, some patients are refractory to benzodiazepine
      treatment due to heavy alcohol abuse. In addition, escalating doses of
      benzodiazepines can lead to respiratory depression, requiring intubation and
      mechanical ventilation. Intubation and mechanical ventilation increase both
      intensive care unit and hospital length of stay. The addition of pharmacological
      agents to reduce the amount of benzodiazepine use in AWS has recently been
      studied. Most recently, the addition of dexmedetomidine, a selective alpha2
      adrenoceptor agonist, has been explored. Dexmedetomidine provides sedation
      without depressing the respiratory system, making it an ideal pharmacological
      agent to use. The addition of dexmedetomidine in adjunct to benzodiazepine use
      has been proven to reduce the amount of benzodiazepine administered, decrease the
      number of patients requiring intubation and mechanical ventilation, and decrease
      length of intensive care unit stay and overall length of hospital stay. However,
      the use of dexmedetomidine has also produced harmful side effects such as
      hypotension and bradycardia. The use of dexmedetomidine in conjunction with
      benzodiazepines in the setting of AWS is promising; however, more research needs
      to be conducted in regard to the safety and efficacy of its use.

PMID- 29200046
TI  - Undergraduate Nursing Students' Perceptions of Individuals With Drug Use
      Problems: Confirming the Factor Structure of the Drug and Drug Problems
      Perception Questionnaire.
AB  - The Drug and Drug Problems Perception Questionnaire (DDPPQ) is a multidimensional
      instrument that measures healthcare providers' attitudes toward working with
      patients who use drugs. Five- and six-subscale versions of the DDPPQ have been
      published. Although the reliability of the DDPPQ subscales was reported to be
      satisfactory, the factor structure of either version was not validated by a
      confirmatory factor analysis. The aim of this study was to examine the internal
      factor structure of the 22-item DDPPQ instrument using a sample of undergraduate
      nursing students. This study was a secondary analysis that utilized baseline data
      from the Addiction Training for Nurses using Screening, Brief Intervention, and
      Referral to Treatment Program. The DDPPQ was administrated during the
      undergraduate nursing students' junior year in a single university setting in
      southwestern Pennsylvania. A sample of 473 students was used in this study. The
      sample was split equally to conduct both principal component analysis (n = 237)
      and confirmatory factor analysis (n = 236). On average, the sample had a mean age
      of 22.9 years and was predominantly female (87.2%) and Caucasian (90.9%). A
      principal component analysis revealed that a five-factor structure had the best
      fit after the removal of two items. Reliabilities of the five subscales ranged
      from alpha = .696 to alpha = .904. Thus, a five-factor structure with removal of
      Items 9 and 19 is recommended when using the DDPPQ with undergraduate nursing
      students.

PMID- 29200047
TI  - Analysis of Health Behavior Theories for Clustering of Health Behaviors.
AB  - OBJECTIVES: The objective of this article was to review the utility of
      established behavior theories, including the Health Belief Model, Theory of
      Reasoned Action, Theory of Planned Behavior, Transtheoretical Model, and Health
      Promotion Model, for addressing multiple health behaviors among people who smoke.
      It is critical to design future interventions for multiple health behavior
      changes tailored to individuals who currently smoke, yet it has not been
      addressed. METHODS: Five health behavior theories/models were analyzed and
      critically evaluated. A review of the literature included a search of PubMed and
      Google Scholar from 2010 to 2016. Two hundred sixty-seven articles (252 studies
      from the initial search and 15 studies from the references of initially
      identified studies) were included in the analysis. RESULT: Most of the health
      behavior theories/models emphasize psychological and cognitive constructs that
      can be applied only to one specific behavior at a time, thus making them not
      suitable to address multiple health behaviors. However, the Health Promotion
      Model incorporates "related behavior factors" that can explain multiple health
      behaviors among persons who smoke. CONCLUSION: Future multiple behavior
      interventions guided by the Health Promotion Model are necessary to show the
      utility and applicability of the model to address multiple health behaviors.

PMID- 29200048
TI  - The Effect of Adolescents' Internet Addiction on Smartphone Addiction.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of adolescents'
      Internet addiction levels on smartphone addiction. METHODS: This study included
      609 students from three high schools that are located in western Turkey. Numbers,
      percentages, and averages were used to evaluate the sociodemographic data. The
      Kolmogorov-Smirnov and Shapiro-Wilk tests were used to determine whether the data
      had a normal distribution. RESULTS: The average age of the participants was 12.3
      +/- 0.9 years. Of them, 52.3% were male, and 42.8% were 10th graders. All
      participants had smartphones, and 89.4% of them connected to the Internet
      continuously with their smartphones. The study found that there was a
      statistically significant correlation between Internet addiction and smartphone
      addiction. ORIGINALITY AND VALUE: It was determined that male adolescents with
      high levels of Internet addiction also had high smartphone addiction levels. On
      the other hand, sociodemographic variables had no statistically significant
      effect on smartphone addiction. A number of studies in the relevant literature
      examined the effects of Internet addiction on adolescents' smartphone addiction.
      However, findings of this study are unique because they are specific to the
      Turkish culture, and there is a limited database in Turkey regarding this issue.
      The researchers believe that the findings of this study will be beneficial to
      show the importance of the issue in the international arena and to guide further
      studies to prevent this addiction because there is no reliable database about
      smartphone addiction in Turkey.

PMID- 29200049
TI  - Psychosocial Factors Affecting Smartphone Addiction in University Students.
AB  - Smartphone addiction is a recent concern that has resulted from the dramatic
      increase in worldwide smartphone use. The purpose of this cross-sectional study
      was to evaluate psychosocial factors affecting smartphone addiction in university
      students. The study was performed among students at the Ondokuz Mayis University
      Samsun School of Health (Samsun, Turkey) on October-December 2015. Four hundred
      ninety-four students possessing smartphones and agreeing to participate were
      included. A sociodemographic data form produced by the authors and consisting of
      10 questions was administered together with a questionnaire involving the
      Smartphone Addiction Scale-Short Version (SAS-SV), the Flourishing Scale, the
      General Health Questionnaire, and the Multidimensional Scale of Perceived Social
      Support. The questionnaires were applied in a class environment at face-to-face
      interviews. SAS-SV scores of 6.47% of students were "significantly higher" than
      the participating group mean SAS-SV score. Multiple regression analysis revealed
      that depression, anxiety and insomnia, and familial social support statistically,
      significantly predicted smartphone addiction. Further studies of smartphone
      addiction in different age groups and with different educational levels are now
      needed.

PMID- 29200051
TI  - Anabolic Steroids: Did Popeye Use Them Too?

PMID- 29200050
TI  - A Call for Compassionate Care.
AB  - The Substance Abuse and Mental Health Services Administration (2014) reported
      that 1.1% of pregnant women used nonprescription opiates (either heroin or
      prescription pills) in the last 30 days. Methadone and buprenorphine are the most
      common treatments for opiate addiction in pregnant women. Reasons for seeking
      opiate maintenance treatment (OMT) include keeping custody of one's children and
      the hope of developing a healthy parenting relationship. Yet, healthcare
      organizations and professionals have mixed opinions regarding health promotion
      within the maternal OMT population. Proper education regarding the growing and
      complex opiate epidemic continues to remain a void for many healthcare
      professionals. It is imperative that nurses who regularly interact with women in
      OMT show compassion and competence. It is important to highlight the universality
      of the challenges and needs of caring for the OMT population. This Perspectives
      column will explore and describe the context of maternal nonprescription opiate
      use and the care mothers in OMT should receive based on established nursing
      ethical standards.

PMID- 29200053
TI  - Nicotine Addiction and E-cigarettes.

PMID- 29200052
TI  - An Interview With E. M. Vitug Garcia.

PMID- 29200054
TI  - Adolescents With Substance Use Disorders.

PMID- 29200057
TI  - 20 Things You Didn't Know About beta-Blockers.

PMID- 29200055
TI  - The Addition of Dexmedetomidine as an Adjunctive Therapy to Benzodiazepine Use in
      Alcohol Withdrawal Syndrome: A Literature Review.
AB  - Alcohol withdrawal syndrome (AWS) is commonly encountered in the intensive care
      unit population.Currently, the mainstay treatment for AWS is the use of
      benzodiazepines. However, some patients are refractoryto benzodiazepine treatment
      due to heavy alcohol abuse. In addition, escalating doses of benzodiazepines can
      lead torespiratory depression, requiring intubation and mechanical ventilation.
      Intubation and mechanical ventilation increaseboth intensive care unit and
      hospital length of stay. The addition of pharmacological agents to reduce the
      amountof benzodiazepine use in AWS has recently been studied. Most recently, the
      addition of dexmedetomidine, aselective alpha2 adrenoceptor agonist, has been
      explored. Dexmedetomidine provides sedation without depressingthe respiratory
      system, making it an ideal pharmacological agent to use. The addition of
      dexmedetomidine in adjunctto benzodiazepine use has been proven to reduce the
      amount of benzodiazepine administered, decrease thenumber of patients requiring
      intubation and mechanical ventilation, and decrease length of intensive care
      unitstay and overall length of hospital stay. However, the use of dexmedetomidine
      has also produced harmful sideeffects such as hypotension and bradycardia. The
      use of dexmedetomidine in conjunction with benzodiazepinesin the setting of AWS
      is promising; however, more research needs to be conducted in regard to the
      safetyand efficacy of its use.

PMID- 29200058
TI  - Symptoms, Nutrition, Pressure Ulcers, and Return to Community Among Older Women
      With Heart Failure at Skilled Nursing Facilities: A Pilot Study.
AB  - BACKGROUND: Mortality rate is high for older women with heart failure (HF) who
      are discharged to skilled nursing facilities (SNFs) after hospitalization, but
      little is known about their symptoms, nutritional factors, and pressure ulcer
      status and whether these variables predict the women's return to the community.
      OBJECTIVES: The aims of this study are to characterize symptoms (ie, dyspnea,
      cognitive dysfunction, depression, and pain) and nutritional and pressure ulcer
      status, evaluate relationships among symptoms, and examine predictors of return
      to the community among older women with HF admitted to SNFs. METHODS: In this
      pilot observational study, data were collected retrospectively from the
      electronic medical records and the Minimum Data Set 3.0. RESULTS: Data were
      obtained for 45 women with HF (mean age, 84.8 years). Frequency of symptoms was
      dyspnea 18%, cognitive dysfunction 20%, depression 5%, and pain 78%. Mean body
      mass index (BMI) was 29.8 kg/m. Frequency of pressure ulcer risk was 85% and 18%
      had pressure ulcers. The 4 symptoms were not significantly related. Younger age
      (odds ratio, 0.90; P = .023) and BMI of 25 kg/m or greater (odds ratio, 5.31; P =
      .017) predicted return to the community. CONCLUSIONS: The women in this study had
      frequent pain, moderately frequent cognitive dysfunction, and high pressure ulcer
      risk. Surprisingly, few women had dyspnea or depression. Women who were younger
      with higher BMI were more likely to return to the community. The study needs to
      be replicated in a larger more diverse group of older patients with HF.

PMID- 29200059
TI  - A Perioperative Medicine Model for Population Health: An Integrated Approach for
      an Evolving Clinical Science.
AB  - Health care delivery in the United States continues to balance on the tight rope
      that connects its transition from volume to value. Value in economic terms can be
      defined as the amount something exceeds its commodity price and is determined by
      extraordinary reputation, quality, and/or service, whereas its destruction can be
      a consequence of poor management, unfavorable policy, decreased demand, and/or
      increased competition. Going forward, payment for health care delivery will
      increasingly be based on services that contribute to improvements in individual
      and/or population health value, and funds to pay for health care delivery will
      become increasingly vulnerable to competitive market forces. Therefore, a
      sustainable population health strategy needs to be comprehensive and thus include
      perioperative medicine as an essential component of the complete cycle of patient
      centered care. We describe a multidisciplinary integrated program to support
      perioperative medicine services that are integral to a comprehensive population
      health strategy.

PMID- 29200060
TI  - Changing Default Ventilator Settings on Anesthesia Machines Improves Adherence to
      Lung-Protective Ventilation Measures.
AB  - Perioperative lung-protective ventilation (LPV) can reduce perioperative
      pulmonary morbidity. We hypothesized that modifying default anesthesia machine
      ventilator settings would increase the use of intraoperative LPV. Default tidal
      volume settings on our anesthesia machines were decreased from 600 to 400 mL, and
      default positive end-expiratory pressure was increased from 0 to 5 cm H2O. This
      modification increased mean positive end-expiratory pressure from 3.1 to 5.0 cm
      H2O and decreased mean tidal volume from 8.2 to 6.7 mL/kg predicted body weight.
      Notably, increased adherence to LPV from 1.6% to 23.0% occurred quickly with the
      rate of increase more than doubling from 1.8% to 3.9% per year.

PMID- 29200061
TI  - Respiratory Gas Analysis-Technical Aspects.
AB  - A technology-focused review of respiratory gas analysis, with an emphasis on
      carbon dioxide analysis, is presented. The measurement technologies deployed
      commercially are highlighted, and the basic principles and technical concerns of
      infrared spectroscopy and mainstream versus sidestream gas sampling are
      discussed. The specifications of particular interest to the clinician, accuracy
      and response time, and the related standard, with typical values for a
      capnometer, are presented. Representative time and volumetric capnograms are
      shown with the clinically relevant parameters described. Aspects of the
      terminology in present-day use and the need for clarity in defining what is a
      breath and an end-tidal value are reviewed. The applications of capnography of
      particular interest to the anesthesiologist are noted, and key references are
      provided. Ongoing developments with respect to respiratory gas analysis, and
      those that will impact it, are noted.

PMID- 29200062
TI  - Is Compliance With Surgical Care Improvement Project Cardiac (SCIP-Card-2)
      Measures for Perioperative beta-Blockers Associated With Reduced Incidence of
      Mortality and Cardiovascular-Related Critical Quality Indicators After Noncardiac
      Surgery?
AB  - BACKGROUND: While continuation of beta-blockers (BBs) perioperatively has become
      a national quality improvement measure, the relationship between BB withdrawal
      and mortality and cardiovascular-related critical quality indicators has not been
      studied in a contemporary cohort of patients undergoing noncardiac surgery.
      METHODS: For this retrospective study, the quality assurance database of a large
      community-based anesthesiology group practice was used to identify 410,288
      surgical cases, 18 years of age or older, who underwent elective or emergent
      noncardiac surgical procedures between January 1, 2009, and December 31, 2014.
      Each surgical case that was withdrawn from BBs perioperatively was propensity
      matched by clinical and surgical characteristics to 4 cases that continued BBs
      perioperatively. Subsequently, multivariable conditional logistic regression
      analyses were performed in the matched cohort to determine the extent to which
      withdrawal of perioperative BBs was independently associated with mortality as
      the primary outcome and cardiovascular-related critical quality indicators as the
      secondary outcome (need for vasopressor, electrocardiographic changes requiring
      treatment, unplanned admission to intensive care unit, postanesthesia care unit
      stay >2 hours, and a combination of cardiac arrest and myocardial infarction)
      within 48 hours postoperatively. RESULTS: Of the 66,755 (16%) cases in the cohort
      admitted on BB therapy, BBs were withdrawn in 3829 (6%) and continued in 62,926
      (94%). Propensity score matching resulted in an analysis cohort of 19,145 cases.
      Withdrawal of perioperative BBs in the multivariable conditional logistic
      regression analysis was significantly associated with an increased risk for
      mortality (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.75-7.35; P =
      .0003), but a significantly decreased risk for need of blood pressure support
      requiring vasopressor initiation (OR, 0.84; 95% CI, 0.76-0.92; P = .0003) and
      extended postanesthesia care unit stay (OR, 0.69; 95% CI, 0.54-0.88; P = .004)
      within 48 hours after noncardiac surgery. CONCLUSIONS: Perioperative withdrawal
      of BBs was associated with increased risk for mortality within 48 hours after
      noncardiac surgery and with decreased risk for need of vasopressor during the
      early postoperative period and a shorter stay in the postanesthesia care unit.

PMID- 29200063
TI  - In Response.

PMID- 29200064
TI  - Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the
      Elderly.
AB  - Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies
      informed consent thresholds of foreseeability in 10%-15% of patients, and
      materiality with new deficits observed in memory and executive function in
      patients with normal test performance beforehand. At present, the only safety
      step to avoid cognitive dysfunction after surgery is to forego surgery, thereby
      precluding the benefits of surgery with removal of pain and inflammation, and
      resumption of normal nutrition, physical activity, and sleep. To assure that
      consent for surgery is properly informed, risks of both cognitive dysfunction and
      alternative management strategies must be discussed with patients by the surgery
      team before a procedure is scheduled.

PMID- 29200065
TI  - Cardiac Arrest in the Operating Room: Part 2-Special Situations in the
      Perioperative Period.
AB  - As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can
      differ greatly in etiology and treatment from what is described by the American
      Heart Association advanced cardiac life support algorithms, which were largely
      developed for use in out-of-hospital cardiac arrest and in-hospital cardiac
      arrest outside of the perioperative space. Specifically, there are several life
      threatening causes of PPCA of which the management should be within the skill set
      of all anesthesiologists. However, previous research has demonstrated that
      continued review and training in the management of these scenarios is greatly
      needed and is also associated with improved delivery of care and outcomes during
      PPCA. There is a growing body of literature describing the incidence, causes,
      treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia,
      massive trauma, and local anesthetic systemic toxicity) and the need for a better
      awareness of these topics within the anesthesiology community at large. As noted
      in part 1 of this series, these events are always witnessed by a member of the
      perioperative team, frequently anticipated, and involve rescuer-providers with
      knowledge of the patient and the procedure they are undergoing or have had.
      Formulation of an appropriate differential diagnosis and rapid application of
      targeted interventions are critical for good patient outcome. Resuscitation
      algorithms that include the evaluation and management of common causes leading to
      cardiac in the perioperative setting are presented. Practicing anesthesiologists
      need a working knowledge of these algorithms to maximize good outcomes.

PMID- 29200066
TI  - Reduced Left Ventricular Global Longitudinal Strain Predicts Prolonged
      Hospitalization: A Cohort Analysis of Patients Having Aortic Valve Replacement
      Surgery.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is often preserved in
      patients with aortic stenosis and thus cannot distinguish between normal
      myocardial contractile function and subclinical dysfunction. Global longitudinal
      strain and strain rate (SR), which measure myocardial deformation, are robust
      indicators of myocardial function and can detect subtle myocardial dysfunction
      that is not apparent with conventional echocardiographic measures. Strain and SR
      may better predict postoperative outcomes than LVEF. The primary aim of our
      investigation was to assess the association between global longitudinal strain
      and serious postoperative outcomes in patients with aortic stenosis having aortic
      valve replacement. Secondarily, we also assessed the associations between global
      longitudinal SR and LVEF and the outcomes. METHODS: In this post hoc analysis of
      data from a randomized clinical trial (NCT01187329), we examined the association
      between measures of myocardial function and the following outcomes: (1) need for
      postoperative inotropic/vasopressor support; (2) prolonged hospitalization (>7
      days); and (3) postoperative atrial fibrillation. Standardized transesophageal
      echocardiographic examinations were performed after anesthetic induction.
      Myocardial deformation was measured using speckle-tracking echocardiography.
      Multivariable logistic regression was used to assess associations between
      measures of myocardial function and outcomes, adjusted for potential confounding
      factors. The predictive ability of global longitudinal strain, SR, and LVEF was
      assessed as area under receiver operating characteristics curves (AUCs). RESULTS:
      Of 100 patients enrolled in the clinical trial, 86 patients with aortic stenosis
      had acceptable images for global longitudinal strain analysis. Primarily, worse
      intraoperative global longitudinal strain was associated with prolonged
      hospitalization (odds ratio [98.3% confidence interval], 1.22 [1.01-1.47] per 1%
      decrease [absolute value] in strain; P = .012), but not with other outcomes.
      Secondarily, worse global longitudinal SR was associated with prolonged
      hospitalization (odds ratio [99.7% confidence interval], 1.68 [1.01-2.79] per 0.1
      second decrease [absolute value] in SR; P = .003), but not other outcomes. LVEF
      was not associated with any outcomes. Global longitudinal SR was the best
      predictor for prolonged hospitalization (AUC, 0.72), followed by global
      longitudinal strain (AUC, 0.67) and LVEF (AUC, 0.62). CONCLUSIONS: Global
      longitudinal strain and SR are useful predictors of prolonged hospitalization in
      patients with aortic stenosis having an aortic valve replacement.

PMID- 29200067
TI  - Randomized Clinical Trial of Preoperative High-Dose Methylprednisolone on
      Postoperative Pain at Rest After Laparoscopic Appendectomy.
AB  - BACKGROUND: Methylprednisolone administered intravenously preoperatively has been
      shown to reduce pain, nausea, and fatigue after elective surgery. We aimed to
      show that 125 mg of methylprednisolone given intravenously 30 minutes before
      laparoscopic surgery for suspected appendicitis would reduce pain at rest during
      the first 3 postoperative days. METHODS: A multicenter, parallel-group, double
      blind, placebo-controlled study was conducted including patients 18 years of age
      and older with an American Society of Anesthesiologist class of I-III undergoing
      laparoscopic surgery for suspected appendicitis. The primary outcome was pain at
      rest measured on the 11-point numerical rating scale 5 times during the first 3
      days after surgery. The effect of 125 mg of methylprednisolone on postoperative
      pain at rest during the first 3 days was assessed using a mixed-effects model
      with time and intervention as main effects. RESULTS: From April 2016 to August
      2016, 78 patients were included, and all were eligible for analysis of the
      primary outcome. The estimated effect of 125 mg of methylprednisolone on pain at
      rest during the first 3 days after surgery was a nonsignificant increase of 0.2
      (95% confidence interval, -0.5 to 0.9; P = .571) on the 11-point numerical rating
      scale. There was no difference between the 2 groups regarding the need for opioid
      agonists during hospital stay on the first postoperative day (P = .381).
      CONCLUSIONS: A 125-mg dose of methylprednisolone given intravenously 30 minutes
      before laparoscopic surgery for appendicitis seemed no better than placebo at
      providing a clinical meaningful reduction in postoperative pain at rest.

PMID- 29200068
TI  - Distracted Doctoring: Returning to Patient-Centered Care in the Digital Age. Do
      We Have Time for This?

PMID- 29200069
TI  - Visualization Improves Supraclavicular Access to the Subclavian Vein in a Mixed
      Reality Simulator.
AB  - BACKGROUND: We investigated whether visual augmentation (3D, real-time, color
      visualization) of a procedural simulator improved performance during training in
      the supraclavicular approach to the subclavian vein, not as widely known or used
      as its infraclavicular counterpart. METHODS: To train anesthesiology residents to
      access a central vein, a mixed reality simulator with emulated ultrasound imaging
      was created using an anatomically authentic, 3D-printed, physical mannequin based
      on a computed tomographic scan of an actual human. The simulator has a
      corresponding 3D virtual model of the neck and upper chest anatomy. Hand-held
      instruments such as a needle, an ultrasound probe, and a virtual camera
      controller are directly manipulated by the trainee and tracked and recorded with
      submillimeter resolution via miniature, 6 degrees of freedom magnetic sensors.
      After Institutional Review Board approval, 69 anesthesiology residents and
      faculty were enrolled and received scripted instructions on how to perform
      subclavian venous access using the supraclavicular approach based on anatomic
      landmarks. The volunteers were randomized into 2 cohorts. The first used real
      time 3D visualization concurrently with trial 1, but not during trial 2. The
      second did not use real-time 3D visualization concurrently with trial 1 or 2.
      However, after trial 2, they observed a 3D visualization playback of trial 2
      before performing trial 3 without visualization. An automated scoring system
      based on time, success, and errors/complications generated objective performance
      scores. Nonparametric statistical methods were used to compare the scores between
      subsequent trials, differences between groups (real-time visualization versus no
      visualization versus delayed visualization), and improvement in scores between
      trials within groups. RESULTS: Although the real-time visualization group
      demonstrated significantly better performance than the delayed visualization
      group on trial 1 (P = .01), there was no difference in gain scores, between
      performance on the first trial and performance on the final trial, that were
      dependent on group (P = .13). In the delayed visualization group, the difference
      in performance between trial 1 and trial 2 was not significant (P = .09);
      reviewing performance on trial 2 before trial 3 resulted in improved performance
      when compared to trial 1 (P < .0001). There was no significant difference in
      median scores (P = .13) between the real-time visualization and delayed
      visualization groups for the last trial after both groups had received
      visualization. Participants reported a significant improvement in confidence in
      performing supraclavicular access to the subclavian vein. Standard deviations of
      scores, a measure of performance variability, decreased in the delayed
      visualization group after viewing the visualization. CONCLUSIONS: Real-time
      visual augmentation (3D visualization) in the mixed reality simulator improved
      performance during supraclavicular access to the subclavian vein. No difference
      was seen in the final trial of the group that received real-time visualization
      compared to the group that had delayed visualization playback of their prior
      attempt. Training with the mixed reality simulator improved participant
      confidence in performing an unfamiliar technique.

PMID- 29200070
TI  - Perioperative Management of the Patient With a Left Ventricular Assist Device for
      Noncardiac Surgery.
AB  - The pandemic of heart failure and the limited options for treatment of end-stage
      disease have resulted in an increase in the utilization of left ventricular
      assist devices (LVADs). Improvements in device technology and patient survival
      have led to an expanding population of patients requiring noncardiac surgery
      while on LVAD therapy, thus leading to a growing need for familiarity with the
      physiology of these patients. This review describes the functional mechanics of
      the most prevalent continuous-flow LVAD, the HeartMate II, and focuses on
      perioperative anesthetic concerns.

PMID- 29200071
TI  - Evidence Basis for Regional Anesthesia in Ambulatory Anterior Cruciate Ligament
      Reconstruction: Part III: Local Instillation Analgesia-A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Local infiltration analgesia offers effective postoperative analgesia
      after knee arthroplasty, but the role of its counterpart, local instillation
      analgesia (LIA), in anterior cruciate ligament reconstruction (ACLR) is unclear.
      This systematic review and meta-analysis evaluates the analgesic benefits of LIA
      for outpatient ACLR. METHODS: We sought randomized controlled trials
      investigating the analgesic effects of LIA versus control in adults having
      outpatient ACLR and receiving multimodal analgesia (excluding nerve blocks, which
      are examined in parts I and II of this project). Cumulative postoperative
      analgesic consumption at 24 hours was designated as a primary outcome. Analgesic
      consumption during postanesthesia care unit stay, proportion of patients
      requiring analgesic supplementation, time-to-first analgesic request, rest pain
      scores during the first 48 hours, hospital length of stay, and incidence of
      opioid-related side effects were analyzed as secondary outcomes and pooled using
      random effects modeling. RESULTS: Eleven randomized controlled trials (515
      patients) were included. Analgesic consumption was selected as the primary
      outcome in 4 trials (36%). Compared to control, LIA reduced the 24-hour morphine
      consumption by a weighted mean difference (95% confidence interval) of -18.0 mg (
      33.4 to -2.6) (P = .02). LIA reduced postanesthesia care unit morphine
      consumption by -55.9 mg (-88.4 to -23.4) (P < .05) and decreased the odds (odds
      ratio [95% confidence interval]) of analgesic supplementation during the first 24
      hours by 0.4 (0.2-0.8) (P = .004). LIA also improved pain scores during the 0-24
      hour interval, most notably at 4 hours (-1.6 [-2.2 to -1.0) (P < .00001).
      CONCLUSIONS: Administering LIA for outpatient ACLR improves postoperative
      analgesia by decreasing opioid consumption and improving pain control up to 24
      hours, with minimal complications. These findings encourage integrating LIA into
      the care standard for ACLR. Questions regarding the ideal LIA components,
      location, and role in the setting of hamstring grafts require further research.

PMID- 29200072
TI  - Tailored Holder for Continuous Echocardiographic Monitoring.
AB  - Hemodynamic monitoring is essential for prompt and effective interventions in
      intensive care unit patients. We developed a custom-made transthoracic
      echocardiography transducer holder consisting of transducer holder and skin patch
      attachment. This holder allowed continuous transthoracic echocardiography
      monitoring in 5 adult patients with circulatory failure due to shock, and 6
      pediatric patients after successful percutaneous closure of a ventricular septal
      defect. One case of an unexpected hemopericardium was promptly diagnosed and
      pericardiocentesis was performed, and 1 patient required extracorporeal membrane
      oxygenation support.

PMID- 29200073
TI  - Decreased Parasympathetic Activity of Heart Rate Variability During Anticipation
      of Night Duty in Anesthesiology Residents.
AB  - BACKGROUND: In residency programs, it is well known that autonomic regulation is
      influenced by night duty due to workload stress and sleep deprivation. A less
      investigated question is the impact on the autonomic nervous system of residents
      before or when anticipating a night duty shift. In this study, heart rate
      variability (HRV) was evaluated as a measure of autonomic nervous system
      regulation. METHODS: Eight residents in the Department of Anesthesiology were
      recruited, and 5 minutes of electrocardiography were recorded under 3 different
      conditions: (1) the morning of a regular work day (baseline); (2) the morning
      before a night duty shift (anticipating the night duty); and (3) the morning
      after a night duty shift. HRV parameters in the time and frequency domains were
      calculated. Repeated measures analysis of variance was performed to compare the
      HRV parameters among the 3 conditions. RESULTS: There was a significant decrease
      of parasympathetic-related HRV measurements (high-frequency power and root mean
      square of the standard deviation of R-R intervals) in the morning before night
      duty compared with the regular work day. The mean difference of high-frequency
      power between the 2 groups was 80.2 ms (95% confidence interval, 14.5-146) and
      that of root mean square of the standard deviation of R-R intervals was 26
      milliseconds (95% confidence interval, 7.2-44.8), with P = .016 and .007,
      respectively. These results suggest that the decrease of parasympathetic activity
      is associated with stress related to the condition of anticipating the night duty
      work. On the other hand, the HRV parameters in the morning after duty were not
      different from the regular workday. CONCLUSIONS: The stress of anticipating the
      night duty work may affect regulation of the autonomic nervous system, mainly
      manifested as a decrease in parasympathetic activity. The effect of this change
      on the health of medical personnel deserves our concern.

PMID- 29200074
TI  - Survival of Staphylococcus epidermidis in Propofol and Intralipid in the Dead
      Space of Intravenous Injection Ports.
AB  - We tested whether propofol or Intralipid inoculated with Staphylococcus
      epidermidis would promote bacterial growth within an intravenous (IV) injection
      hub, a site prone to bacterial contamination. In tubes incubated under optimal
      conditions, S epidermidis exhibited growth in Intralipid, but not in propofol. In
      contrast, within the IV hub incubated with either propofol or intralipid at room
      temperature, S epidermidis bacterial numbers declined with time, and virtually no
      contamination remained after 12 hours. These data suggest that certain IV lines
      are inhospitable for S epidermidis.

PMID- 29200075
TI  - A World of Need.

PMID- 29200076
TI  - Some Cautionary Tales About Ideal Body Weight Dosing of Anesthetic Medications:
      It Is Not All That Ideal!

PMID- 29200078
TI  - Sugammadex and Oral Contraceptives: Is It Time for a Revision of the Anesthesia
      Informed Consent?

PMID- 29200077
TI  - Consensus Statement on Perioperative Use of Neuromuscular Monitoring.
AB  - A panel of clinician scientists with expertise in neuromuscular blockade (NMB)
      monitoring was convened with a charge to prepare a consensus statement on
      indications for and proper use of such monitors. The aims of this article are to:
      (a) provide the rationale and scientific basis for the use of quantitative NMB
      monitoring; (b) offer a set of recommendations for quantitative NMB monitoring
      standards; (c) specify educational goals; and (d) propose training
      recommendations to ensure proper neuromuscular monitoring and management. The
      panel believes that whenever a neuromuscular blocker is administered,
      neuromuscular function must be monitored by observing the evoked muscular
      response to peripheral nerve stimulation. Ideally, this should be done at the
      hand muscles (not the facial muscles) with a quantitative (objective) monitor.
      Objective monitoring (documentation of train-of-four ratio >=0.90) is the only
      method of assuring that satisfactory recovery of neuromuscular function has taken
      place. The panel also recommends that subjective evaluation of the responses to
      train-of-four stimulation (when using a peripheral nerve stimulator) or clinical
      tests of recovery from NMB (such as the 5-second head lift) should be abandoned
      in favor of objective monitoring. During an interim period for establishing these
      recommendations, if only a peripheral nerve stimulator is available, its use
      should be mandatory in any patient receiving a neuromuscular blocking drug. The
      panel acknowledges that publishing this statement per se will not result in its
      spontaneous acceptance, adherence to its recommendations, or change in routine
      practice. Implementation of objective monitoring will likely require professional
      societies and anesthesia department leadership to champion its use to change
      anesthesia practitioner behavior.

PMID- 29200080
TI  - Assessing effect of perioperative glycemic control on adverse outcomes after
      emergency general surgery.

PMID- 29200079
TI  - External validation of a smartphone app model to predict the need for massive
      transfusion using five different definitions.
AB  - BACKGROUND: Previously, a model to predict massive transfusion protocol (MTP)
      (activation) was derived using a single-institution data set. The PRospective,
      Observational, Multicenter, Major Trauma Transfusion database was used to
      externally validate this model's ability to predict both MTP activation and
      massive transfusion (MT) administration using multiple MT definitions. METHODS:
      The app model was used to calculate the predicted probability of MTP activation
      or MT delivery. The five definitions of MT used were: (1) 10 units packed red
      blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score >= 4, (3)
      critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units
      PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted
      probability of MT with observed outcomes. RESULTS: Of 1,245 patients in the data
      set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met
      definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%).
      Regardless of the outcome (MTP activation or MT administration), the predictive
      ability of the app model was consistent: when predicting activation of the MTP,
      the area under the curve for the model was 0.694 and when predicting MT
      administration, the area under the curve ranged from 0.695 to 0.711. CONCLUSION:
      Regardless of the definition of MT used, the app model demonstrates moderate
      ability to predict the need for MT in an external, homogenous population.
      Importantly, the app allows the model to be iteratively recalibrated ("machine
      learning") and thus could improve its predictive capability as additional data
      are accrued. LEVEL OF EVIDENCE: Diagnostic test study/Prognostic study, level
      III.

PMID- 29200081
TI  - PD-1 Inhibitor-associated Myopathies: Emerging Immune-mediated Myopathies.
AB  - Programmed death-1 (PD-1) inhibitors are increasingly used in cancer
      immunotherapy. Various immune-related adverse events are reported, including
      infrequent individual case reports of myositis or rhabdomyolysis. The frequency
      and diagnostic spectrum of immune-related adverse events affecting skeletal
      muscle in PD-1 inhibitor-treated patients are unknown. We searched the Mayo
      Clinic Pharmacy database (2014-2016) to identify patients who developed
      myopathies during or after PD-1 inhibitor therapy. Among 654 cancer patients
      received PD-1 inhibitors (pembrolizumab=389; nivolumab=264; both=1), we
      identified 5 patients (pembrolizumab=5) with biopsy-proven myopathies (2
      necrotizing myopathy, 1 early dermatomyositis, and 2 nonspecific myopathy). Four
      patients developed concomitant autoimmune disorders. Weakness occurred after a
      median of 2 treatments (range, 1-4). All patients had proximal or axial weakness.
      Four patients had either bulbar or extraocular weakness, but only 1 patient had
      acetylcholine receptor antibodies. Creatine kinase levels were elevated in 3
      patients (necrotizing myopathy=2; nonspecific myopathy=1). Brain magnetic
      resonance imaging revealed abnormal T2 signal and enhancement of extraocular
      muscles in 1 patient with ophthalmoparesis. Pembrolizumab was discontinued in all
      patients. All patients received immunosuppressive therapy, with fatal outcome in
      2 necrotizing myopathy patients and favorable outcome in others. We conclude that
      myopathy is a rare, but unique complication of PD-1 inhibitors with frequent
      involvement of extraocular or bulbar muscles, mimicking myasthenia gravis. Muscle
      biopsy is an important test for PD-1 inhibitor-treated patients who develop
      oculobulbar weakness and hyperCKemia, to distinguish patients with necrotizing
      myopathy from myasthenia gravis. Necrotizing myopathy patients may require more
      aggressive immunotherapy due to their grave prognosis.

PMID- 29200082
TI  - Pneumonitis in Irradiated Lungs After Nivolumab: A Brief Communication and Review
      of the Literature.
AB  - Nivolumab is a feasible therapy option in patients with advanced non-small cell
      lung cancer (NSCLC) who progress on first-line treatment. However, there is
      limited information about an overlapping toxicity of PD-1 inhibitors when
      administered following thoracic radiotherapy (TRT). Three of 25 patients with
      advanced NSCLC were treated with palliative or curative intent. Nivolumab was
      initiated as second or third-line therapy after TRT for recurrent or progressive
      disease. All 3 patients developed grade 3 pneumonitis at some point during
      nivolumab therapy. Herein, we describe 3 cases of pneumonitis in patients with
      NSCLC started on nivolumab following TRT. Imaging analysis was strongly
      consistent with heterogenous lung parenchyma changes in the irradiated lung
      volume receiving a total dose of 15-20 Gy. Pulmonary toxicity was manageable;
      however, interruption of immunotherapy was necessary.

PMID- 29200083
TI  - Clinical Outcomes and Intraocular Pressure Control After Scleral-glued
      Intraocular Lens Insertion in Eyes With Pseudoexfoliation.
AB  - PURPOSE: To analyze clinical outcomes and intraocular pressure control following
      scleral-glued intraocular lens (IOL) fixation in eyes with pseudoexfoliation
      (PXF). METHODS: A retrospective chart review and outcome analysis was performed
      on a series of eyes undergoing glue-assisted, scleral-fixated (scleral-glued) IOL
      insertion in the setting of PXF and poor or absent capsular support. RESULTS: In
      total, 28 eyes were included in the study. The indications for scleral-glued IOL
      fixation included late endocapsular IOL dislocation (21/28, 75%), exchange for
      iris-fixated IOL due to complication (4/28, 14%), subluxed crystalline lens
      (2/28, 7%), and aphakia after complicated cataract surgery (1/28, 4%). In total,
      15/28 (54%) eyes had diagnosed preexisting glaucoma at the time of scleral-glued
      surgery. The most common postoperative complication was ocular hypertension
      requiring escalation of medical management, which occurred in 8/28 (29%) eyes. At
      final follow-up, corrected distance visual acuity was equivalent to or improved
      from preoperative measurements in 25/28 (89%) eyes. CONCLUSIONS: The scleral
      glued surgery is a good option for fixating an IOL in eyes with PXF and poor
      zonular integrity or absent capsular support. Special attention should be placed
      on intraocular pressure control following surgery, which can be less predictable
      in PXF eyes with or without preexisting glaucoma.

PMID- 29200084
TI  - Gait Speed Characteristics and Its Spatiotemporal Determinants in Nursing Home
      Residents: A Cross-Sectional Study.
AB  - BACKGROUND AND PURPOSE: Low and slowing gait speeds among nursing home residents
      are linked to a higher risk of disability, cognitive impairment, falls, and
      mortality. A better understanding of the spatiotemporal parameters of gait that
      influence declining mobility could lead to effective rehabilitation and
      preventative intervention. The aims of this study were to objectively quantify
      the spatiotemporal characteristics of gait in the nursing home setting and define
      the relationship between these parameters and gait speed. METHODS: One hundred
      nursing home residents were enrolled into the study and completed 3 habitual gait
      speed trials over a distance of 3.66 m. Trials were performed using an
      instrumented gait analysis. The manner in which the spatiotemporal parameters
      predicted gait speed was examined by univariate and multivariable regression
      modeling. RESULTS: The nursing home residents had a habitual mean (SD) gait speed
      of 0.63 (0.19) m/s, a stride length of 0.83 (0.15) m, a support base of 0.15
      (0.06) m, and step time of 0.66 (0.12) seconds. Multivariable linear regression
      revealed stride length, support base, and step time predicted gait speed (R =
      0.89, P < .05). Step time had the greatest influence on gait speed, with each 0.1
      second decrease in step time resulting in a 0.09 m/s (95% confidence interval,
      0.08-0.10) increase in habitual gait speed. CONCLUSIONS: This study revealed step
      time, stride length, and support base are the strongest predictors of gait speed
      among nursing home residents. Future research should concentrate on developing
      and evaluating intervention programs that were specifically designed to focus on
      the strong predictors of gait speed in nursing home residents. We would also
      suggest that routine assessments of gait speed, and if possible their
      spatiotemporal characteristics, be done on all nursing home residents in an
      attempt to identify residents with low or slowing gait speed.

PMID- 29200085
TI  - Physical and Cognitive Functions, Physical Activity, and Sedentary Behavior in
      Older Adults With Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Older adults with multiple sclerosis (MS) experience age
      related declines in physical and cognitive functions that may be compounded by
      the disease and its progression and worsened by physical inactivity and sedentary
      behavior. However, the extent to which impairments in physical and cognitive
      functions are manifestations of MS and disease progression, reflective of the
      general aging process, or perhaps 2 detrimental processes exacerbating the
      synergistic effects of the other is relatively unknown. This study compared
      physical and cognitive functions, sedentary behavior, and physical activity
      between 40 older adults with MS (ie, 60 years of age and older) and 40 age- and
      sex-matched healthy older adults. We further examined whether physical activity
      and/or sedentary behavior explained differences between groups in physical and
      cognitive functions. METHODS: Participants initially underwent the cognitive
      assessments, followed by the physical function assessments. The order of tests
      was standardized and participants were provided seated-rest between the
      administrations of the physical function assessments. Participants were then
      instructed to wear an accelerometer and document wear time in a log book for a 7
      day period after the testing session. RESULTS: Multivariate analyses of variance
      indicated that older adults with MS (n = 40) performed worse on all measures of
      physical function, and 1 measure of cognitive function (ie, information
      processing speed), compared with healthy controls (n = 40). Older adults with MS
      engaged in less moderate-to-vigorous physical activity, more sedentary behavior,
      and longer duration of long sedentary bouts than healthy controls. Pearson
      correlations demonstrated that levels and patterns of physical activity were
      significantly associated with a majority of physical function variables but not
      cognitive function variables in both older adults with MS and healthy controls
      but to a greater extent in older adults with MS. Partial Pearson correlations
      further demonstrated that levels and patterns of sedentary behavior were
      significantly associated with a majority of physical function variables but not
      cognitive function variables primarily in older adults with MS. Linear regression
      analyses indicated that levels and patterns of physical activity and sedentary
      behavior partially accounted for differences in physical and cognitive function
      variables between older adults with MS and healthy controls. CONCLUSION: There is
      evidence of reduced function in older adults with MS, and this might be partially
      managed by behavioral interventions that target physical activity and sedentary
      behavior for the promotion of healthy aging in older adults with MS.

PMID- 29200086
TI  - Benefits of Electromagnetic Navigational Bronchoscopy for Identifying Pulmonary
      Nodules for Robotic Resections.
AB  - OBJECTIVE: The ability to localize pulmonary nodules via the robotic thoracic
      technique can be challenging at times. This is most evident when nodules are
      small and/or ground glass in nature. Information regarding methods available to
      localize these difficult nodules, while maintaining a minimally invasive robotic
      approach, is limited. METHODS: We describe a diagnostic and therapeutic method of
      combining electromagnetic navigational bronchoscopy with a total minimally
      invasive robotic approach that identifies these difficult-to-localize pulmonary
      nodules. The technique entails the use of electromagnetic navigational
      bronchoscopy to place a pleural dye marker with a subsequent pulmonary resection
      via a robotic thoracic approach. RESULTS: A cohort of 15 patients from August
      2014 to December 2015 was reviewed. These patients underwent the combined
      approach of electromagnetic navigational bronchoscopy followed by a robotic
      pulmonary resection. Fourteen of the 15 patients had a successful combined
      procedure, which was confirmed with pathology. The range of the nodules was 0.8
      to 2 cm. Methylene blue was used for pleural dye marking. On one occasion, the
      pleural dye was not able to be deciphered. There were no complications from
      either the electromagnetic navigational bronchoscopy or robotic portions of the
      procedure. CONCLUSIONS: Pleural dye marking via electromagnetic navigational
      bronchoscopy can provide an effective method for localizing pulmonary nodules,
      while maintaining a minimally invasive robotic approach. This tactic allows one
      to obtain diagnostic tissue more efficiently, while limiting the potential
      inability to localize a nodule.

PMID- 29200087
TI  - Rapid Explantation of Rapid-Deployment Sutureless Valve in Case of Acute
      Endocarditis: How to Remove Safely Sutureless Perceval S Prostheses.
AB  - We report a case of infective endocarditis on a Perceval S aortic valve
      bioprosthesis, and we describe a feasible and useful technique that can help
      remove the infected valve. These maneuvers consist of an "x-movement" reached
      with the aid of anatomical forceps. The risk of infective endocarditis in
      patients with prosthetic valves is a well-known phenomena in cardiac surgery, and
      it can represent a life-threatening event in many cases. According to guidelines,
      an emergency surgical intervention is required in case of high risk of
      embolization, vegetation superior than 1 cm or acute cardiac failure secondary to
      the acute valve dysfunction. In the reported case, the patient was submitted to
      emergency surgery because of vegetation with diameter superior to 1 cm on the
      aortic bioprosthesis. The described "x-movement" technique allowed an easily "en
      block" excision of the damaged bioprostheses together with vegetation, minimizing
      the risk of vegetation fragmentation.

PMID- 29200088
TI  - Totally Thoracoscopic Pulmonary Vein Isolation: A Simplified Technique.
AB  - Since the introduction of thoracoscopic ablation for atrial fibrillation (AF),
      the field of minimally invasive AF treatment has evolved toward an established
      treatment option for AF, with an overall 2-year antiarrhythmic drug free success
      rate of 77%. Complications are usually minor, and the incidence of bleeding
      needing conversion to sternotomy or (mini-)thoracotomy varies between 0% and
      1.6%. Bleeding is often related to encircling the pulmonary veins, which is a
      blind maneuver that has to be done without direct camera vision. We propose here
      a modified surgical technique to simplify the procedure, shorten the operating
      time, and lower the risk of complications.

PMID- 29200089
TI  - Designing a New Model for Clinical Education: An Innovative Approach.
AB  - To keep pace with the ever-changing health care delivery system, it is important
      to transform the way future nurses are educated, both in classroom and in
      clinical settings, to care for people along the life and care continuum, not only
      in acute-care settings. The purpose of this article is to describe a new approach
      to educating baccalaureate nursing students using immersion practicums that
      expose students to population health, transitions of care, care coordination, and
      the multiple roles a nurse engages in along the continuum. The curriculum
      includes 5 immersions, each with a specific life and care continuum focus to
      develop anticipatory thinkers.

PMID- 29200090
TI  - Impact of Peer-Assisted Learning With Standardized Patients in a Prelicensure
      Nursing Course.

PMID- 29200091
TI  - Using the Levels of Sickness Teaching Strategy to Engage Students in Recognizing
      Clinical Deterioration.

PMID- 29200092
TI  - Practical Considerations in Use of Trigger Tool Methodology in the Emergency
      Department.

PMID- 29200093
TI  - Ace Gene Plays A Key Role In Reducing Blood Pressure In Hypertensive Elderlies
      After Resistance Training Resistance Exercise And Ace Polymorphism.
AB  - Hypertension is a difficult disease to control and exercise training plays a key
      role in hypertension control. Some individuals are not responsive to exercise
      training, so we highlight the polymorphism of angiotensin I converting enzyme, as
      a factor responsible for this lack of responsiveness. The aim of this study was
      to evaluate the influence of ACE (I/D) genotypes on effects of resistance
      training on blood pressure and chronic inflammation. Eighty-six hypertensive
      volunteers, aged between 60 and 80, were evaluated. They performed 16 weeks of
      resistance training at 50% of 1 maximal repetition. The greatest benefits were
      seen on homozygous of the Insertion allele, whom presented reduction of systolic
      blood pressure (SBP: 129.31+/-13.34 vs. 122.56+/-9.68 mmHg, p<0.001) and
      diastolic blood pressure (DBP: 79.18+/-8.05 vs. 70.12+/-7.71 mmHg, p<0.01) during
      daytime period, and in 24h period (SBP: 127.12+/-13.65 vs. 121.06+/-9.68 mmHg,
      p<0.001 and DBP: 71.87+/-8.39 vs. 68.75+/-8.72 mmHg, p<0.05) and also increased
      circulating adiponectin levels (4.04+/-1.79 vs. 6.00+/-2.81 ng/mL, p<0.01). Other
      genotypes showed no changes in blood pressure and biochemical parameters. Our
      results suggest a cardio protective factor of I allele, since only those
      homozygous showed reductions in blood pressure and increases in adiponectin.

PMID- 29200094
TI  - Characteristics of a National Level Female Weightlifter Peaking for Competition:
      A Case Study.
AB  - This study investigated physiological and performance changes of a national level
      69kg female weightlifter following three competition phases over a 28-week
      training period. The athlete first trained for a regional championship (weeks 1
      12), followed by a local competition (weeks 13-23) and the national championship
      (weeks 24-28). Body mass, vastus lateralis cross-sectional area, and unloaded and
      loaded squat jump performance were assessed weekly during each 4-week competition
      phase. Serum biomarkers, and dynamic mid-thigh pulls were assessed prior to and
      after each competition phase. Weightlifting performance goals were met for the
      regional championship (total=200kg) and the local competition (total=193kg), but
      not the national championship (total=196kg). She lost more body mass in
      preparation for nationals (-6.0kg) compared to regionals (-2.5kg) and the local
      competition (+2.2kg). Vastus lateralis cross-sectional area very likely decreased
      following nationals (precision=99%, effect size=2.08). Her testosterone:cortisol
      ratio likely increased (88%, 2.64), while interleukin-6 (79%, 2.47), and tumor
      necrosis factor-alpha (81%, 3.59) likely decreased following nationals. Serum
      myostatin (99%, 1.95) and decorin (99%, 1.96) very likely decreased following the
      local competition. Unloaded squat jump height likely increased the week of
      regionals (89%, 0.95) and the local competition (99%, 1.83), whereas unloaded and
      loaded squat jump height possibly (69%, 0.99) and likely (82%, 1.52) decreased
      the week of nationals. Dynamic mid-thigh pull vertical displacement likely
      increased following regionals (93%, 0.84), and likely decreased following
      nationals (94%, 0.87). These findings indicate that biomarkers of stress,
      inflammation, and hypertrophy are related to changes in training volume-load;
      however, performance measures are needed to assess competition preparedness.
      Considering the reductions in muscle cross-sectional area corresponding with the
      large reductions in body mass and underperformance at the national championship,
      sport scientists and coaches should instruct weightlifters to not attempt large
      losses in body mass (e.g. >3 kg) close to competition (e.g. <1 week).

PMID- 29200095
TI  - Widespread spontaneous hyperproliferation, melanosis and melanoma in Hgf-Cdk4R24C
      mice.

PMID- 29200096
TI  - TGF-beta1 protection against Abeta1-42-induced hippocampal neuronal inflammation
      and apoptosis by TbetaR-I.
AB  - Alzheimer's disease (AD), the most common chronic neurodegenerative disease, is
      pathologically characterized by the formation of neurofibrillary tangles because
      of hyperphosphorylation of tau protein and extracellular deposits of amyloid-beta
      (Abeta) protein termed senile plaques. Recent studies indicate that neuronal
      apoptosis caused by chronic neuroinflammation is one of the important
      pathogenesis of AD. Transforming growth factor (TGF)-beta1 is a pleiotropic
      cytokine with immunosuppressive and anti-inflammatory properties. However, it is
      poorly known whether the anti-inflammatory property of TGF-beta1 is involved in a
      neuroprotection in AD. Here, an AD cell model of hippocampal neurons induced by
      Abeta1-42 was used to show an anti-inflammatory and neuroprotective effect of TGF
      beta1 through its receptor transforming growth factor-beta receptor type I
      (TbetaR-I). As expected, Abeta1-42-induced an upregulation in neuronal expression
      of amyloid precursor protein (APP), tumor necrosis factor-alpha, cyclooxygenase
      2, Bax, cleaved caspase-3, and cleaved caspase-9, and a downregulation in the
      expression of Bcl-2, as well as an increase in the number of NeuN/terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL) double-positive cells. TGF-beta1 pretreatment reduced the Abeta1
      42-induced effects of upregulating APP, tumor necrosis factor-alpha, Bax, cleaved
      caspase-3 and cleaved caspase-9, and downregulating Bcl-2, in addition to
      increasing NeuNTUNEL cell number. TbetaR-I expression in hippocampal neurons was
      downregulated by Abeta1-42 exposure, but upregulated by TGF-beta1 pretreatment.
      Silencing of the TbetaR-I gene in the neurons abolished the anti-inflammatory and
      antiapoptotic effects of TGF-beta1 in the Abeta1-42-induced AD cell model. These
      findings suggest that TGF-beta1 protects neurons against Abeta1-42-induced
      neuronal inflammation and apoptosis by activation of TbetaR-I.

PMID- 29200097
TI  - External Evaluation of Population Pharmacokinetic Models of Infliximab in
      Patients With Inflammatory Bowel Disease.
AB  - BACKGROUND: Infliximab (IFX) trough levels vary markedly between patients with
      inflammatory bowel disease (IBD), which is important for clinical response. The
      aim of this study was to evaluate the performance of previously developed
      population pharmacokinetic models in patients with IBD for dose individualization
      for Crohn disease (CD) and ulcerative colitis in our clinical setting. METHODS:
      The authors collected 370 trough levels prospectively from 100 adult patients
      with IBD who were undergoing IFX treatment between July 2013 and August 2016. The
      external evaluation included prediction- and simulation-based diagnostics
      [prediction-corrected visual predictive check, prediction- and variability
      corrected visual predictive check, and normalized prediction distribution error
      tests]. RESULTS: In prediction-based diagnostics, the authors observed a
      nonsignificant overall mean relative bias of -6.87% and an acceptable imprecision
      of 8.45%. Approximately 100% of the prediction error was within +/-30%,
      indicating satisfactory predictability. Simulation-based diagnostics indicated
      model misspecification; thus, the model may not be appropriate for simulation
      based applications. CONCLUSIONS: While simulation-based diagnostics provided
      unsatisfactory results, the prediction-based diagnostics demonstrate that the
      population pharmacokinetic model developed by Fasanmade et al for CD can be used
      to predict and design individualized IFX dose regimens that meet the individual
      needs of patients with CD and ulcerative colitis.

PMID- 29200098
TI  - PREOPERATIVE FACTORS INFLUENCING VISUAL RECOVERY AFTER VITRECTOMY FOR MYOPIC
      FOVEOSCHISIS.
AB  - PURPOSE: To determine the preoperative factors influencing visual recovery after
      vitrectomy for myopic foveoschisis. METHODS: Sixty-six eyes of 65 consecutive
      patients operated on for myopic foveoschisis were retrospectively included. All
      eyes underwent a preoperative ocular examination including best-corrected visual
      acuity (BCVA) and spectral domain optical coherence tomography with central
      foveal thickness measurement and foveal status classification: simple
      foveoschisis, foveal detachment, or macular hole. To study the impact of
      preoperative visual acuity, 4 visual acuity groups separated by quartile ranges
      were defined. Postoperative visits at 1, 3, or 12 months including BCVA
      measurement and optical coherence tomography were recorded. RESULTS: Mean
      refraction was -15.90 diopters, mean axial length was 30.30 mm, mean central
      foveal thickness was 590 MUm, and mean baseline logarithm of the maximum angle of
      resolution visual acuity was 0.68 (Snellen equivalent of 20/96). The final BCVA
      improved significantly from 3 months after surgery until the last follow-up
      visit; the mean logarithm of the maximum angle of resolution visual acuity at
      last follow-up was 0.43 (Snellen equivalent of 20/54). Mean central foveal
      thickness decreased significantly as soon as the first postoperative month (P <
      0.0001). The preoperative BCVA was the only independent factor significantly
      correlated with the final BCVA as opposed to the foveal status (P < 0.0001). The
      mean BCVA and mean visual gain at the last follow-up visit were significantly
      different between the four visual acuity groups (P < 0.0001 and P = 0.017,
      respectively). CONCLUSION: The main factor influencing the postoperative visual
      acuity is the preoperative visual acuity. Although the preoperative anatomical
      status seemed important in surgeon decision making, once normalized on visual
      acuity, it no longer influenced the postoperative visual acuity.

PMID- 29200099
TI  - ANALYSIS OF THE NORMAL PERIPHERAL RETINAL VASCULAR PATTERN AND ITS CORRELATION
      WITH MICROVASCULAR ABNORMALITIES USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY.
AB  - PURPOSE: To describe the retinal peripheral vascular morphology and to elucidate
      its relationship to microvascular abnormalities in normal fundus using ultra
      widefield fluorescein angiography. METHODS: A total of 242 eyes from 167
      consecutive patients were categorized into 3 groups: bilateral normal (n = 64),
      normal with contralateral eye affected with vascular disease (n = 82), and early
      diabetic eyes (n = 96). Peripheral vascular morphology was described and
      classified according to the shape. Microvascular abnormalities such as capillary
      telangiectasia, microaneurysm, or vascular leakage were documented, and the
      relationship between those abnormalities in each groups were analyzed. RESULTS:
      There were two distinctive peripheral vascular morphologies-loop and branching
      patterns. Microvascular abnormalities were more frequently found as loop
      patterns; this difference was most prominent when both eyes were normal. In case
      of normal eyes with contralateral eye affected with vascular disease or diabetic
      eyes, branching pattern microvascular abnormalities were relatively increased,
      whereas loop pattern still showed a large degree of microvascular abnormalities.
      CONCLUSION: In normal retinal periphery, we observed microvascular abnormalities
      and their relationship with vascular morphology, which could be influenced by the
      condition of the contralateral eye or systemic disease such as diabetes mellitus.

PMID- 29200100
TI  - Diagnostic and Therapeutic Challenges.

PMID- 29200101
TI  - Modeling Continuous Prognostic Factors in Survival Analysis: Implications for
      Tumor Staging and Assessing Chemotherapy Effect in Osteosarcoma.
AB  - Extent of response to neoadjuvant chemotherapy, tumor size, and patient age are
      important prognostic variables for patients with osteosarcoma, but applying
      information from these continuous variables in survival models is difficult.
      Dichotomization is usually inappropriate and alternative statistical techniques
      should be considered instead. Nonlinear multivariable regression methods
      (restricted cubic splines and fractional polynomials) were applied to data from
      the National Cancer Database to model continuous prognostic factors for overall
      survival from localized, high-grade osteosarcoma of the appendicular and
      nonspinal skeleton following neoadjuvant chemotherapy and surgical resection
      (N=2493). The assumption that log hazard ratios were linear in relation to these
      continuous prognostic factors was tested using likelihood ratio tests of model
      deviance and Wald tests of spline coefficients. Log hazard ratios for increasing
      patient age were linear over the range of 4 to 80 years, but showed evidence for
      variation in the coefficient over elapsed follow-up time. Tumor size also showed
      a linear relationship with log hazard over the range of 1 to 30 cm. Hazard ratios
      for chemotherapy effect profoundly deviated from log-linear (P<0.004), with
      significantly decreased hazard for death from baseline for patients with >=90%
      tumor necrosis (hazard ratio, 0.32; 95% confidence interval, 0.20-0.52;
      P<0.0001). Important implications of these results include: (1) >=90% tumor
      necrosis defines good chemotherapy response in a clinically useful manner; (2)
      staging osteosarcoma by dichotomizing tumor size is inappropriate; and (3)
      patient age can be modeled as a linear effect on the log hazard ratio in
      prognostic models with the caveat that risk may change over duration of the
      analysis.

PMID- 29200102
TI  - Adult Primary Immune Thrombocytopenia: Spleen Histology Findings and Outcomes
      According to Rituximab Use Based on Analysis of 41 Cases.
AB  - Immune thrombocytopenia (ITP) is an acquired antibody-mediated disease, for which
      splenectomy remains a curative treatment. We analyzed histology and phenotypes of
      ITP-splenectomy specimens from 41 adult patients, with different previous ITP
      specific treatments, including B-cell-depleting rituximab (RTX) or not, in an
      attempt to predict splenectomy success or failure on the basis of day 56
      postoperative platelet counts. RTX-naive ITP-spleen samples, compared with those
      from a 20-patient control trauma cohort, contained the following nonspecific, ITP
      evocative, white-pulp lesions: follicular helper T-cell (programmed death-1 and
      inducible T-cell COStimulator) expansion in reactive follicles (P=0.01 and 0.03,
      respectively) and regulatory T-cell (FOXP3) expansion in the T-cell zone
      (P=0.049). On comparing ITP-splenectomy samples that would be successful with
      those that would be failures, only marginal zone hyperplasia differed (P=0.017).
      Indeed, 13/21 (61.9%) successful splenectomy samples exhibited marginal zone
      hyperplasia, as opposed to 1/9 (11.1%) failed splenectomy specimens. RTX impact
      on ITP-splenectomy samples was characterized by white-pulp (P=0.03) and marginal
      zone atrophies (P=0.01), and periarteriolar T-cell-zone hyperplasia (P<0.0001).
      The results of this novel comparative study of the histologic patterns of 41 ITP
      patients' evocative splenic lesions enabled clear description of different ITP
      morphologies and phenotypes, as a function of prior treatment and splenectomy
      success or failure.

PMID- 29200103
TI  - BCOR Internal Tandem Duplication in High-grade Uterine Sarcomas.
AB  - Endometrial stromal sarcomas (ESSs) are mesenchymal uterine tumors characterized
      by recurrent genetic events, most commonly chromosomal rearrangements, that
      create oncogenic gene fusions. High-grade endometrial stromal sarcomas (HG-ESSs),
      as defined in the 2014 World Health Organization Classification, typically
      contain oncogenic YWHAE-NUTM2 fusions; however, although not well characterized,
      there are tumors morphologically overlapping with HG-ESS that do not contain the
      YWHAE-NUTM2 fusions. These fusions are also found in certain pediatric primitive
      sarcomas, including clear cell sarcoma of the kidney and soft tissue
      undifferentiated round cell sarcoma of infancy. A subset of these same pediatric
      sarcomas lack YWHAE-NUTM2 fusions and instead have internal tandem duplications
      (ITDs) involving exon 15 of BCOR (BCOR ITD). We investigated the presence of BCOR
      ITD by targeted sequencing in a series of 31 uterine sarcomas, comprising 5 low
      grade ESS, 13 uterine sarcomas diagnosed as HG-ESS, and 13 undifferentiated
      uterine sarcomas. BCOR ITD were present in 1 uterine sarcoma diagnosed as HG-ESS
      and 2 undifferentiated sarcomas with uniform nuclear features, all of which
      lacked any of the recurrent chromosome translocations known to occur in ESS.
      These 3 high-grade sarcomas with BCOR ITD affected young patients (average age,
      24) and morphologically were composed of nonpleomorphic spindle cells admixed
      with epithelioid and round cell areas. Focal myxoid stroma was present in 2
      cases. Mitotic activity was brisk, necrosis was present, and there was
      lymphovascular involvement in all cases. The 3 uterine sarcomas with BCOR ITD
      exhibited diffuse cyclin D1 immunohistochemical expression and there was diffuse
      BCOR expression in the 2 cases tested. Long-term follow-up in 2 patients revealed
      1 to be tumor-free after 22 years and the other to die of disease after 8 years.
      In conclusion, BCOR ITD is an oncogenic alternative to YWHAE-NUTM2 fusion in high
      grade uterine sarcomas with uniform nuclear features. We propose that neoplasms
      with the morphology described and BCOR ITD be regarded as a unique subtype of
      high-grade uterine sarcoma, possibly within the family of endometrial stromal
      neoplasia.

PMID- 29200108
TI  - Oncology Recapitulates Neurology.

PMID- 29200109
TI  - 2016 World Health Organization Classification of Central Nervous System Tumors.
AB  - PURPOSE OF REVIEW: Since 1979, the World Health Organization (WHO) has
      periodically published a consensus classification and grading of tumors of the
      central nervous system (CNS) to ensure uniform histopathologic diagnostic
      criteria worldwide. In 2016, the WHO published an update of the fourth edition of
      the classification of CNS tumors. This article summarizes the major changes in
      the update and discusses their impact on clinical practice. RECENT FINDINGS: For
      the first time, the 2016 revision of the WHO classification uses molecular
      parameters in addition to traditional histology to diagnose many CNS tumors,
      resulting in major restructuring of the classification of many tumors, especially
      gliomas, ependymomas, and medulloblastomas. Accordingly, nomenclature for
      selected entities now includes both a histopathologic diagnosis and defining
      molecular features. SUMMARY: The use of integrated phenotypic and genotypic
      parameters for the classification of CNS tumors introduces greater objectivity to
      the diagnosis but also requires more widespread availability of molecular
      testing. It is hoped that these changes will lead to greater diagnostic accuracy
      with more biologically homogeneous diagnostic entities and improved patient
      management and determination of prognosis.

PMID- 29200110
TI  - High-grade Gliomas.
AB  - PURPOSE OF REVIEW: This article reviews the standard treatment for high-grade
      gliomas, with a focus on promising new strategies and response assessment. RECENT
      FINDINGS: The new World Health Organization (WHO) classification of central
      nervous system tumors classifies high-grade gliomas based on molecular markers
      that are of prognostic and therapeutic significance. The addition of
      chemotherapy, specifically procarbazine, CCNU (lomustine), and vincristine, to
      radiation in newly diagnosed 1p/19q codeleted anaplastic oligodendrogliomas
      doubled overall survival. The US Food and Drug Administration (FDA) recently
      approved the addition of tumor treating fields to adjuvant temozolomide after
      radiation with concurrent temozolomide in newly diagnosed glioblastoma. A phase3
      trial for recurrent glioblastoma did not show an overall survival benefit for the
      addition of bevacizumab to lomustine compared to lomustine alone. Current efforts
      are focused on the development of novel treatment approaches, including molecular
      targeted agents and immunotherapies. SUMMARY: Surgery, radiation, and
      chemotherapy remain the standard treatment options for patients with high-grade
      gliomas. Despite aggressive treatment, these tumors progress, and overall
      outcomes have not changed much in the past decade. However, our understanding of
      the disease is improving, and newer therapies appear promising.

PMID- 29200111
TI  - Low-grade Gliomas.
AB  - PURPOSE OF REVIEW: Low-grade gliomas present vexing management issues for neuro
      oncologists. The relatively long survival compared to other brain tumors makes
      consideration of treatment toxicity, and thus timing of potentially damaging
      interventions such as surgery, radiation, and chemotherapy, crucial. Moreover,
      the rarity of these tumors makes clinical trials to ascertain optimal care
      challenging. RECENT FINDINGS: The discovery that most low-grade gliomas harbor
      isocitrate dehydrogenase (IDH) mutations that confer a favorable prognosis has
      improved diagnosis and risk stratification of these tumors. Although Level 1
      evidence is still lacking, increasing data support the concept of maximal safe
      tumor debulking as a first step in tumor management. Preliminary results from a
      large randomized trial suggest chemotherapy is of comparable effectiveness to
      radiation therapy for one molecular subtype of low-grade glioma. Importantly,
      however, the final results of a phase 3 trial comparing radiation with or without
      procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy indicate a
      large survival advantage to combined chemotherapy and radiation, raising
      questions about using chemotherapy alone as an initial treatment strategy.
      SUMMARY: While the combination of radiation and PCV provides the best proven
      overall survival with low-grade gliomas, important questions remain. These
      include whether the better-tolerated temozolomide is as effective as PCV in
      conjunction with radiation therapy and whether the use of initial chemotherapy as
      a strategy to defer the potential delayed cognitive toxicity associated with
      radiation will yield acceptable survival results with a favorable toxicity
      profile.

PMID- 29200112
TI  - Epidemiology, Treatment, and Complications of Central Nervous System Metastases.
AB  - PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases
      to brain parenchyma, dura, spinal cord, and leptomeninges are among the most
      common types of consultations addressed by neurologists. With patients surviving
      longer from systemic cancer, along with the rapidly evolving therapeutic options,
      the treatment of these devastating complications has become both more effective
      and more complicated. This article reviews current patterns of metastatic disease
      and the increasingly nuanced landscape of evolving therapies, their
      complications, and their impact on quality of survival. RECENT FINDINGS: Targeted
      therapies with tyrosine kinase inhibitors and immune checkpoint inhibitors and
      cytotoxic therapies directed at disease-specific chemosensitivity patterns have
      dramatically improved the prognosis of non-small cell lung cancer, melanoma, and
      breast cancer, but have led to some novel complications and altered recurrence
      patterns. Clinical trials suggest the superiority of hippocampal-avoidance
      radiation fields and the use of stereotactic radiosurgery over whole-brain
      radiation therapy to minimize long-term cognitive consequences of radiation
      therapy. Emerging data document tolerable safety when brain radiation is combined
      with immunotherapy. Chemotherapy can be a first-line treatment for some
      inoperable brain metastases, eliminating or deferring whole-brain radiation
      therapy. Stereotactic body radiation therapy is a new technique of radiation used
      for spinal and epidural metastases that spares spinal cord tissue while ablating
      tumors. SUMMARY: Metastases to the nervous system remain devastating, but their
      prognosis and therapies are more heterogeneous than previously appreciated.
      Neurologists now can offer more personalized prognostic information based on new
      stratification criteria, can predict drug complications relevant to the nervous
      system, and can provide critical partnership in the multidisciplinary effort to
      balance effective longer-term disease control with treatment-related adverse
      consequences.

PMID- 29200113
TI  - Primary Central Nervous System Lymphoma.
AB  - PURPOSE OF REVIEW: Primary central nervous system (CNS) lymphoma is a rare and
      aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, spinal
      cord, or leptomeninges without systemic involvement. This article provides an
      overview of the clinical features, diagnosis, and management of primary CNS
      lymphoma in patients who are immunocompetent, focusing on recent advances in
      treatment. RECENT FINDINGS: Primary CNS lymphoma is sensitive to radiation
      therapy; however, whole-brain radiation therapy inadequately controls the disease
      when used alone and causes delayed neurotoxicity with significant neurocognitive
      impairment, especially in patients who are elderly. A number of clinical trials
      have demonstrated durable disease control and less neurotoxicity with
      methotrexate-based induction chemotherapy with or without autologous stem cell
      transplantation or reduced-dose whole-brain radiation therapy. SUMMARY: Prompt
      diagnosis and initiation of treatment are vital to improving clinical outcomes in
      patients with primary CNS lymphoma. The optimal treatment has yet to be defined,
      but high-dose methotrexate-based induction chemotherapy is considered standard
      for newly diagnosed primary CNS lymphoma. Ongoing randomized trials will attempt
      to address the roles of rituximab and consolidative treatment using autologous
      stem cell transplantation or reduced-dose whole-brain radiation therapy. Despite
      high tumor response rates to initial treatment, many patients will relapse. The
      choice of salvage treatment will depend on age, previous treatment and response,
      performance status, and comorbidities at the time of relapse.

PMID- 29200114
TI  - Neuroradiologic Pearls for Neuro-oncology.
AB  - PURPOSE OF REVIEW: This article reviews key principles in the identification of
      tumors of the central nervous system (CNS) using standard and advanced imaging
      modalities. This article highlights the pitfalls and pearls of the imaging
      evaluation of patients with cancer at time of diagnosis and during cancer therapy
      and discusses the challenges of the imaging evaluation of treatment-related
      toxicities. RECENT FINDINGS: Treatment of CNS tumors with surgery, chemotherapy,
      or radiation alters the imaging appearance of the tumor and can be associated
      with a variety of treatment-related toxicities. The clinician must be familiar
      with how to assess response to treatment and how to differentiate tumor
      progression from treatment-related effects. SUMMARY: Management and follow-up of
      neuro-oncology patients is optimized by a comprehensive radiologic approach to
      CNS tumors and recognition of the challenges in the assessment of response to
      treatments.

PMID- 29200115
TI  - Medical Complications of Brain Tumors.
AB  - PURPOSE OF REVIEW: This article discusses common and emergent medical
      complications encountered in patients with primary brain tumors. RECENT FINDINGS:
      Clinical studies and systematic reviews published in recent years have improved
      knowledge regarding the incidence of neurologic and medical complications
      occurring in patients with primary brain tumors. Studies in tumor-related
      epilepsy and venous thromboembolism provide data for the clinician to make
      evidence-based decisions about perioperative management, prophylaxis, and
      therapy. Patients with brain tumors experience unique toxicities related to novel
      drugs and chemotherapeutics that result in hematologic, infectious, and endocrine
      disorders. Recent work that has focused on quality of life in patients with brain
      tumors highlights the importance of good supportive care and optimal medical
      management of neurobehavioral symptoms and late complications of treatment.
      SUMMARY: A thorough understanding of the variety of medical and neurologic
      complications in patients with primary brain tumors improves the clinician's
      ability to quickly recognize and manage common and urgent conditions.

PMID- 29200116
TI  - Paraneoplastic Disorders.
AB  - PURPOSE OF REVIEW: Paraneoplastic neurologic syndromes target specific areas of
      the nervous system with pathogenic autoantibodies or T-cell responses. Each
      syndrome conveys a risk of particular tumors. Expanded paraneoplastic antibody
      testing has led to improved diagnosis but created challenges involving
      appropriate interpretation of test results. RECENT FINDINGS: Peripheral nervous
      system paraneoplastic disorders such as myasthenia gravis and Lambert-Eaton
      myasthenic syndrome involve pathogenic autoantibodies. Recently, the pathogenic
      mechanisms and antigens of these disorders have been further elucidated.
      Paraneoplastic syndromes associated with onconeuronal antibodies, such as anti
      Hu, have strong cancer associations and limited response to treatment.
      Autoimmunity to central nervous system membrane proteins, such as the N-methyl-D
      aspartate (NMDA) receptor or leucine-rich, glioma inactivated 1 (LGI1), defines
      an expanding group of disorders with better prognosis and more variable cancer
      associations. In these diseases, the autoantibodies are either proven to be or
      are potentially pathogenic. An animal model of anti-NMDA receptor encephalitis
      will allow novel treatments to be developed. Autoantibodies to intracellular
      synaptic antigens, such as glutamic acid decarboxylase 65 (GAD65), are associated
      with diverse disorders such as stiff person syndrome, and the pathophysiology of
      these diseases is unclear. SUMMARY: Paraneoplastic disorders have diverse
      clinical manifestations, including weakness, sensory neuronopathy, encephalitis,
      epilepsy, and psychosis. Proper use of antibody testing may assist with
      diagnosis. Treatment may require immunotherapy and tumor treatment.

PMID- 29200117
TI  - Common Histologically Benign Tumors of the Brain.
AB  - PURPOSE OF REVIEW: As a group, benign tumors account for the majority of primary
      neoplasms affecting the central nervous system (CNS). This article reviews the
      epidemiology, clinical presentation, neuroimaging features, and management of the
      most common of these tumors: meningiomas, schwannomas, and pituitary adenomas.
      RECENT FINDINGS: Awareness of the most common nonmalignant tumors of the CNS and
      their management guidelines is important as many of these tumors are managed
      conservatively, with neurologists playing a primary role in both surveillance and
      symptom management. Knowledge of the varied neurologic consequences of these
      tumors allows optimizing interventions that improve quality of life in people
      living with these tumors without incurring treatment-related complications.
      Awareness of the clinical features that require surgery, radiation therapy, or
      chemotherapy is imperative. Finally, important discoveries in both germline and
      somatic mutations underlying some of these lesions have contributed to the launch
      of several novel drug trials for these tumors. SUMMARY: As a group, nonmalignant
      neoplasms are the most common neoplasms affecting the CNS in adults. Because of
      their unique neuroanatomic location or containment within the bony skull, these
      histologically benign lesions can cause significant neurologic morbidity.
      Management with a multidisciplinary team that includes neurologists, neuro
      oncologists, radiologists, neurosurgeons, radiation oncologists,
      otolaryngologists, pathologists, neuropsychologists, physiatrists, and others is
      necessary for the optimal management of these lesions.

PMID- 29200118
TI  - Palliative Care, End-of-Life Care, and Advance Care Planning in Neuro-oncology.
AB  - PURPOSE OF REVIEW: Despite new therapeutic approaches, most patients with high
      grade glioma face limited overall survival and have a high symptom burden
      throughout their disease trajectory, especially in the end-of-life phase. This
      article provides an overview of the role of palliative care in neuro-oncology.
      Management recommendations are made for neurologic symptoms in patients with
      advanced brain tumors, including headaches, nausea, and fatigue. Special
      attention is given to how and when to involve subspecialty palliative care and
      hospice services to improve symptom management during active tumor treatment and
      in the end-of-life phase of patients with brain tumors. Advance care planning and
      end-of-life goals should be addressed early in the disease trajectory; this
      article provides a road map for these discussions. RECENT FINDINGS: The high
      symptom burden of patients with brain tumors affects their quality of life as
      well as their ability to make treatment decisions. It is therefore warranted to
      involve patients with high-grade glioma in treatment decision making early in the
      disease course, with a focus on end-of-life care and advance care planning.
      Research in other World Health Organization grade IV cancers has shown that the
      early involvement of specialty palliative care improves quality of life and
      caregiver satisfaction. Patients with brain tumors should be actively screened
      for fatigue, and underlying factors such as hormone deficiencies, low blood
      counts, and sleep issues should be addressed before focusing interventions for
      tumor- and treatment-related fatigue. SUMMARY: Palliative care can address
      typical symptoms, such as fatigue, nausea, and headaches that have the potential
      to severely disable patients with brain tumors. Advance care planning should be
      introduced proactively and early in the disease trajectory to ensure a dignified
      death and improved caregiver bereavement.

PMID- 29200120
TI  - APPENDIX A: An Oncologic Reference for Neurologists.

PMID- 29200119
TI  - Pediatric Brain Tumors.
AB  - PURPOSE OF REVIEW: This article describes the most common pediatric brain tumors
      and highlights recent developments in their diagnosis and treatment strategies.
      RECENT FINDINGS: We are in the midst of a molecular era for pediatric brain
      tumors. Genetic and epigenetic profiling of tumors has impacted their diagnosis,
      allowing for the subgrouping of heterogeneous tumor groups and leading to the
      complete renaming of some tumor types. These advances are reflected in the new
      2016 World Health Organization classification. For example, primitive
      neuroectodermal tumors have been completely eliminated and replaced by subgroups
      defined by the absence or presence of specific chromosomal amplification.
      Medulloblastomas, diffuse astrocytomas, and ependymomas now have specific
      subtypes that are based on defining molecular features. More recent epigenetic
      based subgrouping of atypical teratoid/rhabdoid tumors have not yet made it into
      the official classification system, but will surely have an impact on how these
      tumors are regarded in future preclinical and clinical trials. SUMMARY: Genetic
      and epigenetic data are changing how pediatric brain tumors are diagnosed, are
      leading to new guidelines for how treatment outcome analyses can be organized,
      and are offering molecular targets that can be used for the development of novel
      therapies.

PMID- 29200121
TI  - APPENDIX B: Useful Websites for Oncology Patients and Providers.

PMID- 29200125
TI  - Patient Management Problem.

PMID- 29200126
TI  - Patient Management Problem-Preferred Responses.

PMID- 29200128
TI  - TRO40303 Ameliorates Alcohol-Induced Pancreatitis Through Reduction of Fatty Acid
      Ethyl Ester-Induced Mitochondrial Injury and Necrotic Cell Death.
AB  - OBJECTIVES: Mitochondrial permeability transition pore inhibition is a promising
      approach to treat acute pancreatitis (AP). We sought to determine (i) the effects
      of the mitochondrial permeability transition pore inhibitor 3,5-seco-4-nor
      cholestan-5-one oxime-3-ol (TRO40303) on murine and human pancreatic acinar cell
      (PAC) injury induced by fatty acid ethyl esters (FAEEs) or taurolithocholic acid
      3-sulfate and (ii) TRO40303 pharmacokinetics and efficacy in experimental
      alcoholic AP (FAEE-AP). METHODS: Changes in mitochondrial membrane potential
      (Deltapsim), cytosolic Ca ([Ca]c), and cell fate were examined in freshly
      isolated murine or human PACs by confocal microscopy. TRO40303 pharmacokinetics
      were assessed in cerulein-induced AP and therapeutic efficacy in FAEE-AP induced
      with palmitoleic acid and ethanol. Severity of AP was assessed by standard
      biomarkers and blinded histopathology. RESULTS: TRO40303 prevented loss of
      Deltapsim and necrosis induced by 100 MUM palmitoleic acid ethyl ester or 500 MUM
      taurolithocholic acid-3-sulfate in murine and human PACs. Pharmacokinetic
      analysis found TRO40303 accumulated in the pancreas. A single dose of 3 mg/kg
      TRO40303 significantly reduced serum amylase (P = 0.043), pancreatic trypsin (P =
      0.018), and histopathology scores (P = 0.0058) in FAEE-AP. CONCLUSIONS: TRO40303
      protects mitochondria and prevents necrotic cell death pathway activation in
      murine and human PACs, ameliorates the severity of FAEE-AP, and is a candidate
      drug for human AP.

PMID- 29200129
TI  - The Effect of Pancreatic Juice Collection Time on the Detection of KRAS
      Mutations.
AB  - OBJECTIVE: Secretin-stimulated pancreatic juice is collected from the duodenum
      and analyzed to identify biomarkers of pancreatic neoplasia, but the optimal
      duration of pancreatic juice collection is not known. METHODS: We compared the
      yield of KRAS mutations detected in pancreatic juice samples aspirated from near
      the duodenal papilla at 1 to 5, 6 to 10, and 11 to 15 minutes after secretin
      infusion, and from the third part of the duodenum (at 15 minutes) from 45
      patients undergoing endoscopic ultrasound pancreatic surveillance. KRAS mutation
      concentrations were measured by using droplet digital polymerase chain reaction.
      RESULTS: Forty of 45 patients had KRAS mutations detected in their pancreatic
      juice, and most patients' juice samples had more than 1 KRAS mutation. Of 106
      KRAS mutations detected in 171 pancreatic juice samples, 58 were detected in the
      5-minute samples, 70 mutations were detected in the 10-minute samples, and 65
      were detected in the 15-minute samples. Nine patients who did not have KRAS
      mutations detected in their 5-minute sample had mutations detected in samples
      collected at later time points. Ninety-percent of all pancreatic juice mutations
      detected in any sample were detected in the 5- or 10-minute samples. CONCLUSIONS:
      Collecting pancreatic juice for 10 minutes after secretin infusion increases the
      likelihood of detecting pancreatic juice mutations over shorter collections.

PMID- 29200130
TI  - DIFFUSE RETINAL VASCULAR LEAKAGE AND CONE-ROD DYSTROPHY IN A FAMILY WITH THE
      HOMOZYGOUS MISSENSE C.1429G>A (P.GLY477ARG) MUTATION IN CRB1.
AB  - PURPOSE: To describe a specific cone-rod dystrophy phenotype in a family with the
      homozygous c.1429G>A; p.Gly477Arg mutation in CRB1. The detailed phenotype of
      subjects with this specific mutation has not been described previously. METHODS:
      Clinical examination included full-field electroretinography and high-resolution
      and widefield retinal imaging and uveitis workup. Molecular genetic analysis
      included next-generation sequencing of known retinal dystrophy genes and Sanger
      sequencing for segregation analysis. RESULTS: Three affected male siblings (26,
      16, and 8 years old) were diagnosed with cone-rod dystrophy, featuring bilateral
      macular hypoautofluorescent lesions. In addition, the eldest brother was found to
      have retinal vascular leakage throughout the retina without telangiectasia.
      Uveitis laboratory workup was unremarkable. The homozygous c.1429G>A; p.Gly477Arg
      mutation in CRB1 was found to segregate with disease in this family. CONCLUSION:
      To the best of our knowledge, diffuse vascular leakage without telangiectasia or
      exudation, with bull's eye maculopathy, has not been reported previously in CRB1
      cone rod dystrophy. This expands the phenotype complexity associated with CRB1
      mutations and confirms that dystrophies associated with mutations in this gene
      may appear with features of uveitis.

PMID- 29200131
TI  - Validation of an Algorithm to Identify Infective Endocarditis in People Who
      Inject Drugs.
AB  - INTRODUCTION: Infective endocarditis is associated with high morbidity and
      mortality. Currently, there is concern that the incidence of infective
      endocarditis associated with people who inject drugs (PWID) is increasing.
      However, it is difficult to monitor population-wide trends in PWID-associated
      infective endocarditis, as there is no International Statistical Classification
      of Diseases, 10th Revision (ICD-10) code for injection drug use. To address this
      barrier, we sought to develop a validated algorithm using ICD-10 discharge
      diagnosis codes. MATERIALS AND METHODS: We constructed a cohort of patients whose
      hospital discharge diagnosis included infective endocarditis. We reviewed 100
      patients with incident infective endocarditis from 2014 to 2016 for their
      infective endocarditis and injection drug use status. We calculated the operating
      characteristics for algorithms constructed using permutations of ICD-10 codes
      associated with injection drug use. We repeated this analysis in a cohort of 100
      patients with incident infective endocarditis from 2009 to 2011 to examine the
      temporal stability of the operating characteristics of each algorithm. RESULTS:
      We found that a combination of hepatitis C virus, drug use, and mental/behavioral
      disorder codes yielded the highest sensitivity (93%) and positive predictive
      value (83%) of the algorithms analyzed. DISCUSSION: We have described the first
      algorithm, validated against chart review data, for identifying PWID-associated
      infective endocarditis cases using ICD-10 codes. The high sensitivity and
      positive predictive value indicate that this algorithm can be used for
      surveillance and research with confidence. CONCLUSIONS: This algorithm will
      enable researchers to examine epidemiological trends in PWID-associated infective
      endocarditis.

PMID- 29200132
TI  - A Practical Comparison Between the Predictive Power of Population-based Risk
      Stratification Models Using Data From Electronic Health Records Versus
      Administrative Claims: Setting a Baseline for Future EHR-derived Risk
      Stratification Models.

PMID- 29200133
TI  - Toluene Diisocyanate Exposure: Exposure Assessment and Development of Cross
      Facility Similar Exposure Groups Among Toluene Diisocyanate Production Plants.
AB  - OBJECTIVE: The objective of this study was to characterize workplace toluene
      diisocyanate (TDI) exposures using standardized industrial hygiene exposure
      assessment procedures for use in a prospective epidemiologic study of
      occupational asthma. METHODS: Over 2300 representative routine full shift time
      weighted average (TWA) and short-term high potential exposure tasks (HPETs) air
      samples in groups across three TDI plants were collected over a nearly 7-year
      period. RESULTS: Data-derived similar exposure groups (SuperSEGs) were developed
      across the plants based on TWA sampling using cluster analysis. Individual
      cumulative exposure estimates were developed on the basis of the SuperSEGs.
      CONCLUSION: Workplace TWA exposures to TDI were adequately characterized
      quantitatively, but HPET exposures were adequately characterized only by
      qualitative measures. The mean TWA exposure was 0.65 parts per billion for 1594
      routine samples. These TWA and HPET exposures can be used to support exposure
      response analyses.

PMID- 29200134
TI  - Medical Monitoring for Occupational Asthma Among Toluene Diisocyanate Production
      Workers in the United States.
AB  - OBJECTIVE: The aim of this study was to describe a study of medical monitoring
      methods and lessons learned in detecting health outcomes in U.S. plants producing
      toluene diisocyanate (TDI). METHODS: A multidisciplinary team implemented a
      medical and environmental monitoring program in three TDI plants. RESULTS: Of 269
      eligible workers, 197 (73%) participated and 42 (21%) met symptom and/or lung
      function criteria that would trigger evaluation for possible asthma over 5 years
      of data collection. Subsequent evaluation was delayed for most, and a web-based
      data collection system improved timeliness. CONCLUSION: Medical monitoring of TDI
      workers identified workers triggering further assessment per study protocol.
      Systems and/or personnel to ensure rapid follow-up are needed to highlight when
      triggering events represent potential cases of asthma needing further evaluation.
      Implementation of a research protocol requires resources and oversight beyond an
      occupational health program.

PMID- 29200137
TI  - Early Prediction of Persistent Organ Failure by Circulating Endothelial
      Progenitor Cells in Patients With Acute Pancreatitis.
AB  - INTRODUCTION: Increased circulating endothelial progenitor cells (cEPC) have been
      observed in patients with vascular injury associated with sepsis and acute lung
      injury. However, a role for cEPC in severe acute pancreatitis (SAP) remains
      unclear. We therefore conducted a prospective study to study whether the
      quantities of cEPC can predict persistent organ failure (POF) in patients with
      predicted SAP. METHODS: A total of 42 predicted SAP patients who were admitted
      within 24 h after symptom onset and 10 healthy control subjects were enrolled in
      our study. The proportions of cEPC were analyzed based on flow cytometry
      simultaneously. Vascular endothelial growth factor (VEGF) levels were measured by
      enzyme-linked immunosorbent assay. RESULTS: The percentage of cEPC was
      significantly higher in patients with predicted SAP compared with healthy
      controls. Similarly, the levels of VEGF in peripheral blood were also
      significantly higher in predicted SAP patients than in the controls. Notably,
      patients with POF had lower proportion of cEPC compared with patients with
      transient organ failure (TOF). In contrast, patients with POF had a significantly
      higher level of VEGF compared with TOF. Of note, the percentages of cEPC were
      significantly inversely correlated with disease severity scores. More
      importantly, cEPC showed an excellent discriminative power for predicting POF
      among predicted SAP patients, whereas plasma VEGF and disease severity scores
      showed moderate accuracy in predicting future POF. CONCLUSIONS: Peripheral EPC as
      a novel biomarker is elevated and may aid to predict the development of POF in
      patients with predicted SAP.

PMID- 29200135
TI  - Incidence of Occupational Asthma and Exposure to Toluene Diisocyanate in the
      United States Toluene Diisocyanate Production Industry.
AB  - OBJECTIVE: This study examines asthma risk in facilities producing toluene
      diisocyanate (TDI). METHODS: A total of 197 workers were monitored from 2007 to
      2012. TDI air concentrations were used to estimate exposures. RESULTS: The
      incidence of cases consistent with TDI-induced asthma was 0.009 per person-years
      (seven cases) or consistent with TDI-induced asthma or asthma indeterminate
      regarding work-relatedness was 0.012 (nine cases). Increased risk of cases
      consistent with TDI asthma was observed for cumulative (odds ratio [OR] = 2.08,
      95% confidence interval [CI] 1.07 to 4.05) per logarithm parts per billion-years
      and peak TDI exposures (OR = 1.18, 95% CI 1.06 to 1.32) (logarithm parts per
      billion). There was a weak association with cumulative and peak exposures for
      decline of short-term forced expiratory volume in one second (FEV1). Asthma
      symptoms were associated with workers noticing an odor of TDI (OR 6.02; 95% CI
      1.36 to 26.68). CONCLUSIONS: There is evidence that cumulative and peak exposures
      are associated with TDI-induced asthma.

PMID- 29200138
TI  - Dispatcher-Assisted Cardiopulmonary Resuscitation Program and Outcomes After
      Pediatric Out-of-Hospital Cardiac Arrest.
AB  - OBJECTIVES: A dispatcher-assisted bystander cardiopulmonary resuscitation (DA
      BCPR) is expected to influence the outcomes of pediatric out-of-hospital cardiac
      arrest (OHCA). Our objective was to measure the effect size of a DA-BCPR on
      survival outcomes according to location of the event. METHODS: All emergency
      medical service treated OHCA patients younger than 19 years in Korea from January
      2012 through December 2013 were analyzed. Patients with OHCA witnessed by
      emergency medical service providers and those with missing outcome information
      were excluded. Patients were categorized into the following categories: No-BCPR,
      BCPR without dispatcher assistance (BCPR-NDA), and BCPR-DA. The primary outcome
      was survival to hospital discharge. Multivariable logistic regression analysis
      was performed to calculate the adjusted odds ratios (AORs) and 95% confidence
      intervals (CIs) for outcomes by exposure group (reference, No-BCPR group) with
      and without an interaction term between exposure and location of arrest. RESULTS:
      A total of 1013 eligible patients were analyzed. Among these patients, 16.6%
      received BCPR-NDA, 23.2% received BCPR-DA, and 60.2% received no BCPR. After
      adjusting for potential confounders, compared with N0-BCPR group, AORs for
      survival were 1.79 (95% CI, 1.03-3.12) in BCPR group, 1.71 (95% CI, 0.85-3.46) in
      BCPR-NDA group, and 1.39 (95% CI, 0.72-2.69) in BCPR-DA group. The AORs for
      survival of BCPR-NDA and BCPR-DA in public location were 3.30 (95% CI, 1.12-9.72)
      and 2.95 (95% CI, 1.00-8.67), whereas BCPR-NDA and BCPR-DA in private locations
      were 1.62 (95% CI, 0.68-3.88) and 1.15 (95% CI, 0.53-2.51). CONCLUSION: The DA
      CPR was associated with better outcomes in pediatric OHCA patients whose arrest
      occurred in public locations, but no improvement in outcomes was identified in
      patients whose arrest occurred at private locations.

PMID- 29200136
TI  - Longitudinal and Cross-sectional Analyses of Lung Function in Toluene
      Diisocyanate Production Workers.
AB  - OBJECTIVE: The aim of this study was to investigate lung function among toluene
      diisocyanate (TDI) production workers. METHODS: One hundred ninety-seven U.S
      workers performed spirometry from 2006 through 2012. Results were compared within
      the study cohort and with U.S. population measures. A mixed-effects model
      assessed factors affecting repeated forced expiratory volume in 1 second (FEV1)
      measurements. RESULTS: The cohort's mean FEV1 and forced vital capacity (FVC)
      percent reference values, although greater than 90%, were significantly lower and
      the prevalence of abnormal spirometry (predominantly restrictive pattern) was
      significantly higher than in the U.S. POPULATION: Differences in lung function
      among workers with higher cumulative TDI exposure were in the direction of an
      exposure effect, but not significant. CONCLUSION: We found little evidence of an
      adverse effect of TDI exposure on longitudinal spirometry in these workers. The
      association between TDI exposure and the increasing prevalence of a restrictive
      pattern needs further exploration.

PMID- 29200139
TI  - Hyperkalemia and Acute Kidney Injury in an Adolescent: Thinking Outside the Box.
AB  - Addison disease is a rare endocrine disorder, which typically presents with
      nonspecific symptoms including weight loss, fatigue, and nausea in conjunction
      with hyponatremia and hyperkalemia. This case demonstrates key diagnostic clues
      in evaluation of an adolescent who presented with severe hyperkalemia and acute
      kidney injury that was resistant to insulin, glucose, and sodium polystyrene
      sulfonate and was found to have primary adrenal insufficiency.

PMID- 29200141
TI  - Effects of the Introduction of Intranasal Fentanyl on Reduction of Pain Severity
      Score in Children: An Interrupted Time-Series Analysis.
AB  - OBJECTIVES: Children are at risk of inadequate analgesia due to paramedics'
      inexperience in assessing children and challenges in administering analgesics
      when the patient is distressed and uncooperative. This study reports on the
      outcome of a change to practice guidelines that added intranasal fentanyl and
      intramuscular morphine within a large statewide ambulance service. METHODS: This
      retrospective study included patients younger than 15 years treated by paramedics
      between January 2008 and December 2011. The primary outcome of interest was the
      proportion of patients having a 2/10 or greater reduction in pain severity score
      using an 11-point Verbal Numeric Rating Scale before and after the intervention.
      Segmented regression analysis was used to estimate the effect of the intervention
      over time. A multiple regression model calculated odds ratios with 95% confidence
      intervals. RESULTS: A total of 92,378 children were transported by paramedics
      during the study period, with 9833 cases included in the analysis. The median age
      was 11 years; 61.6% were male. Before the intervention, 88.1% (n = 3114) of
      children receiving analgesia had a reduction of pain severity of 2 or more
      points, with 94.2% (n = 5933) achieving this benchmark after intervention (P <
      0.0001). The odds of a reduction in pain of 2 or more points increased by 1.01
      per month immediately before the intervention and 2.33 after intervention
      (<0.0001). CONCLUSIONS: This large study of a system-wide clinical practice
      guideline change has demonstrated a significant improvement in the outcome of
      interest. However, a proportion of children with moderate to severe pain did not
      receive analgesia.

PMID- 29200140
TI  - Evaluating the Implementation Barriers of an Intranasal Fentanyl Pain Pathway for
      Pediatric Long-Bone Fractures.
AB  - OBJECTIVES: This study aimed to assess physician comfort, knowledge, and
      implementation barriers regarding the use of intranasal fentanyl (INF) for pain
      management in patients with long-bone fractures in a pediatric emergency
      department (ED) with an INF pain pathway. METHODS: A retrospective chart review
      was conducted of patients, 3 to 21 years old, in our ED with an International
      Classification of Diseases-9th Revision code for a long-bone fracture from
      September 1, 2013, to August 31, 2015. Patients were divided into 4 groups: (1)
      received INF on the pathway appropriately; (2) "missed opportunities" to receive
      INF, defined as either INF was ordered and then subsequently canceled (for pain
      ratings, >=6/10), or INF was ordered, cancelled, and intravenous (IV) morphine
      given, or INF was not ordered and a peripheral IV line was placed to give IV
      morphine as first-line medication; (3) peripheral IV established upon ED arrival;
      (4) no pain medication required. Additionally, a survey regarding practice habits
      for pain management was completed to evaluate physician barriers to utilization
      of the pathway. RESULTS: A total of 1374 patients met the inclusion criteria.
      Missed opportunities were identified 41% of the time. Neither younger patient age
      nor more years of physician experience in the ED were associated with increased
      rates of missed opportunities. The survey (95% response rate) revealed greater
      comfort with and preference for IV morphine over INF. CONCLUSIONS: The high rate
      of missed opportunities, despite the implementation of an INF pain pathway,
      indicates the need for further exploration of the barriers to utilization of the
      INF pain pathway.

PMID- 29200142
TI  - Burnout Rates in Pediatric Emergency Medicine Physicians.
AB  - OBJECTIVE: Burnout is a syndrome in which a reduced sense of personal
      accomplishment, depersonalization, and emotional exhaustion develop in response
      to prolonged stress. It is well known that physicians suffer high rates of
      burnout; emergency medicine physicians experience significantly increased rates
      of burnout, whereas physicians in other specialties, like pediatrics, may be
      spared. Pediatric emergency medicine physicians are on the frontline of care for
      the critically ill child, which could put them at high risk for burnout. This
      study evaluates the rate of burnout in pediatric emergency medicine physicians.
      METHODS: We conducted a survey assessing burnout using a sample of pediatric
      emergency medicine physicians who subscribe to an open Listserv server maintained
      by Brown University. Burnout was measured using a validated instrument, the
      Maslach Burnout Inventory-Human Services Survey, which was distributed by e-mail
      to the study group. RESULTS: Respondents averaged a score of 9 (95% confidence
      interval [CI], 8-10), 23 (95% CI, 21-25), and 39 (95% CI, 38-40) in the subscales
      of depersonalization, emotional exhaustion, and personal accomplishment,
      respectively. This placed our cohort into the average range for all subscales.
      The percentage of respondents who scored in the high levels of burnout (moderate
      to high scores in both depersonalization and emotional exhaustion and low to
      moderate scores in personal accomplishment) was 25% (95% CI, 18-32). CONCLUSIONS:
      Unlike previous literature showing burnout prevalence in excess of 60% in
      emergency medicine physicians and 38% in pediatricians, our pediatric emergency
      medicine physicians fared better with only 25% (95% CI, 18-32), showing elevated
      levels of burnout.

PMID- 29200143
TI  - The Predictors for Positive Yield Abdominal Computed Tomography in Pediatric
      Abdominal Trauma.
AB  - OBJECTIVES: Abdominal computed tomography (ACT) use in the initial evaluation of
      pediatric abdominal trauma is liberal in most instances. The aim of this study
      was to identify the predictors for a positive yield ACT scan in this population.
      METHODS: A prospective, cohort, single-center observational study was conducted
      at Children's Hospital at Westmead, New South Wales, from January 2008 to June
      2015 on 240 pediatric abdominal trauma patients who had abdominal computed
      tomography. Clinical, laboratory, imaging, and interventional variables were
      explored with univariate and multivariate analyses among children who sustained
      abdominal trauma. RESULTS: Of 240 patients, positive ACT scans were found in 161
      patients (67%), 112 patients (47%) had intra-abdominal injury, and 20 patients
      (8%) required invasive therapeutic interventions. Mortality rate was 1.7% (4
      patients) due to nonabdominal causes. Multivariate analyses revealed that
      increasing age (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.02-1.24; P
      = 0.024), high injury severity score (OR, 1.14; 95% CI, 1.07-1.21; P < 0.001),
      abnormal abdominal examination (OR, 5.95; 95% CI, 2.08-17.01; P = 0.001),
      elevated alanine aminotransferase greater than 125 IU/L (OR, 46.28; 95% CI, 2.81
      762.49; P = 0.007), abnormal pelvic radiograph (OR, 14.03; 95% CI, 2.39-82.28; P
      = 0.003), presence of gross hematuria (OR, 4.14; 95% CI, 1.04-18.23; P = 0.044),
      low initial hematocrit level (less than 30%) (OR, 8.51; 95% CI, 1.14-63.70; P =
      0.037), and positive focused assessment with sonography for trauma (OR, 2.61; 95%
      CI, 1.01-7.28; P = 0.048) remained significantly associated with abnormal ACT
      scan. In contrast, those who required scanning of other body region(s) were less
      likely to have abnormal ACT scan (OR, 0.34; 95% CI, 0.14-0.86; P =0.022).
      CONCLUSIONS: Integrating the abdominal examination findings, relevant laboratory
      values, and focused assessment with sonography for trauma results with the
      physicians' suspicion may aid in stratifying patients for ACT scan. Further
      efforts should be made to decrease number of normal ACT scans; yet not to
      increase the number of delayed or missed injures with its inherent morbidity and
      mortality.

PMID- 29200144
TI  - Clinical Challenges: Identification of Patients With Novel Primary
      Immunodeficiency Syndromes.
AB  - Novel primary immunodeficiency disorders are being identified with next
      generation sequencing technologies. We describe 1 patient with cytotoxic T
      lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency who had recurrent
      enhancing brain lesions, nodular pulmonary infiltrates, hepatosplenomegaly,
      immune cytopenias, as well as progressive hypogammaglobulinemia and lymphopenia.
      We describe a second patient with activated p110delta syndrome (APDS)/p110delta
      activating mutation causing senescent T cells, lymphadenopathy, and
      immunodeficiency (PASLI) in association with recurrent respiratory tract
      infections, Epstein-Barr virus infection, lymphadenopathy, elevated serum IgM,
      and progressive lymphopenia. These presentations highlight the need for astute
      clinical judgment in the evaluation of patients with potential primary
      immunodeficiency disorders.

PMID- 29200145
TI  - Treatment Outcome of Children With Multisystem Langerhans Cell Histiocytosis: The
      Experience of a Single Children's Hospital in Shanghai, China.
AB  - We reported the outcome of 150 children newly diagnosed with multisystem
      langerhans cell histiocytosis following a langerhans cell histiocytosis-II-based
      protocol (arm B). However, the continuation treatment was extended to 56 weeks
      and etoposide was omitted from the continuation treatment. Risk organ (RO)
      involvement was defined as: liver (>=3 cm with or without functional impairment);
      spleen (>=2 cm below the costal margin in the midclavicular line); hematopoietic
      system (hemoglobin <100 g/L, and/or white blood cell count <4.0*10/L, and/or
      platelets <100*10/L). The lungs are not considered a RO in the current study. For
      the 59 patients with RO involvement (RO+), the rapid response rate (week 6) was
      61.0% and the 3-year overall survival 73.4%+/-5.9%. Rapid responders had a better
      3-year survival rate than poor responders (90.9%+/-5.0% vs. 45.7%+/-11.0%,
      P<0.001). Ninety-one patients without RO involvement (RO-) had a relatively low 3
      year cumulative reactivation rate (10.7%). No deaths occurred in this subgroup
      and the 3-year overall survival of RO- patients was 100%. Poor responders of RO+
      patients had an extremely poor prognosis. An effective salvage therapy is
      essential for this high-risk group. The initial treatment intensity and duration
      of continuation therapy both impact disease reactivation in RO- patients.

PMID- 29200146
TI  - Successful Treatment of Mediastinal gammadelta T-Cell Lymphoblastic Lymphoma in a
      3-Year-Old Girl by Allogeneic Cord Blood Transplantation.
AB  - A 3-year-old girl presenting with a huge mediastinal tumor and massive pleural
      effusion, was diagnosed with stage III gammadelta T-cell lymphoblastic lymphoma
      (gammadelta T-LBL) by flow cytometry of effusion cells. Four courses of
      chemotherapy achieved complete remission, and 5/6 HLA allele-matched cord blood
      transplantation was performed with success. The patient remains in first complete
      remission >16 months after transplantation. gammadelta T-LBL is very rare,
      especially that of mediastinal origin, and is acknowledged as having an extremely
      poor clinical outcome. The present case study is the first to report the
      successful treatment of mediastinal gammadelta T-LBL in a toddler.

PMID- 29200147
TI  - Pediatric Deep Venous Thrombosis Associated With Staphylococcal Infections:
      Single Institutional Experience.
AB  - Deep venous thrombosis (DVT) has been previously reported in children with
      methicillin-resistant Staphylococcus aureus (MRSA). This study reviews our
      institutional experience by evaluating characteristics and outcomes of children
      with DVT and staphylococcal infections. Retrospective clinical data from 16
      pediatric patients with DVT and staphylococcal infections over a 5-year period
      was obtained via medical record abstraction. Sixteen patients with a median age
      at diagnosis of 8 years were included. The most common infection encountered was
      osteomyelitis (56%). The most common isolated organism was MRSA (63%). Central
      venous catheters were present in 50% of cases. All patients received
      anticoagulation with low molecular weight heparin except 1 patient with
      superficial venous thrombosis who was managed conservatively. Fifty percent of
      patients had complete resolution of DVT by the end of treatment, 25% of the
      patients had early disappearance of the thrombus at 7 to 10 days. Only 2 patients
      (12.5%) had persistent thrombus at 6 months. Staphylococcal infections may
      increase the risk of DVT in children. Therefore, a high index of suspicion for
      DVT is warranted in children with Staphylococcal infections (particularly MRSA)
      to promptly diagnose, treat and minimize complications. Prophylactic
      anticoagulation in presence of staphylococcal infection, particularly MRSA, may
      be considered in future studies.

PMID- 29200148
TI  - Macrothrombocytopenia With Congenital Bilateral Cataracts: A Phenotype of MYH9
      Disorder With Exon 24 Indel Mutations.
AB  - MYH9 disorder is characterized by large platelets and granulocyte inclusion
      bodies, and can be complicated with young-adult onsets of nephropathy,
      sensorineural hearing loss, and cataracts. Congenital cataracts in patients with
      MYH9 disorder is rare, and their etiology has not been elucidated. We report a 3
      year-old patient with MYH9 disorder who had a p.E1066_A1072del mutation and
      developed cataracts congenitally. A review of the literature reveals that
      patients with an MYH9 exon 24 indel mutation, including p.E1066_A1072del, are
      susceptible to developing congenital cataracts and should be followed closely for
      other nonhematological complications.

PMID- 29200149
TI  - Childhood and Adolescent Cancer in the State of Pernambuco, Brazil: Incidence,
      Geographical Distribution, and Association With Environmental Health Indicators.
AB  - Cases of childhood and adolescent cancer diagnosed from 2009 to 2012 in the state
      of Pernambuco, Brazil, were analyzed considering the patients' sex and age, the
      type of cancer and the municipality of living to determine the incidence,
      geographical distribution, and association with environmental health indicators.
      The spatial distribution pattern of the cancer incidence was estimated using the
      Global Moran's index. The association between environmental health indicators and
      cancer incidence was evaluated by multiple regression. From 2009 to 2012, 1261
      new cases of cancer were diagnosed in patients younger than 20 years old in the
      state of Pernambuco. Leukemia/lymphoma were the most common type of cancer
      contemplating 45.28% of the cases. The average age-adjusted incidence rate was
      113 cases per million with no spatial distribution pattern. The municipalities
      were clustered according to their degree of inequality (P=0.017), human
      development index (P=0.001), population growth rate (P=0.008), urbanization level
      (P=0.001), number of agricultural crops per capita (P=0.001), and number of
      industries per capita (P=0.030). However, only urbanization level was positive
      correlated with incidence of pediatric cancer (P=0.009) likely because in more
      developed cities, people are more exposed to potential oncogenic factors, such as
      air and water pollution and processed and ultraprocessed food. The better access
      to specialized health services, which increases the chances of early diagnosis,
      may also contributes for a higher number of cases in more developed cities.

PMID- 29200150
TI  - Alder-Reilly Anomaly in the Cerebrospinal Fluid of a Child With Hurler Syndrome.
AB  - Hurler syndrome is an autosomal recessive mucopolysaccharidosis characterized by
      intralysosomal accumulation of glycosaminoglycan fragments, with cellular
      accumulation of distended lysosomes resulting in interference with normal cell
      function. One of the peripheral blood features of mucopolysaccharidoses is the
      presence of numerous, dark lilac granules within lymphocytes, monocytes, and
      neutrophils, also known at Alder-Reilly anomaly. Here we describe
      intracytoplasmic granules with haloes in mononuclear cells present in the
      cerebrospinal fluid of a 2-year-old boy with the diagnosis of Hurler syndrome,
      undergoing pretransplant evaluation for an unrelated donor cord blood stem cell
      transplant.

PMID- 29200151
TI  - Recurrent Acute Chest Syndrome in Pediatric Sickle Cell Disease: Clinical
      Features and Risk Factors.
AB  - Acute chest syndrome (ACS) is a common and serious lung complication in sickle
      cell disease. A retrospective medical chart review was performed over a 6-year
      period in all pediatric ACS patients to investigate whether factors during the
      initial hospitalization were associated with recurrent ACS episodes. There were
      386 episodes of ACS: 149 had only 1 episode of ACS, and 76 had >1 episode of ACS;
      172 (76.4%) had hemoglobin SS, and 39 (17.3%) had hemoglobin SC. The most common
      presenting features were fever (83%), pain (70%), and cough (61%), which changed
      with the number of ACS episodes. Children <4 years old were at greatest risk of
      recurrent ACS (P=0.018). In addition, history of asthma (adjusted incident rate
      ratio [IRR]=1.52; 95% confidence interval [CI], 1.22-1.98; P<0.0001), shortness
      of breath (IRR, 1.29; 95% CI, 1.02-1.62; P=0.033), and length of hospital stay
      (IRR, 1.04; 95% CI, 1.01-1.08; P=0.017) were significantly associated with
      prospective ACS events. Multiple episodes of ACS are common in sickle cell
      disease, and certain risk factors during the initial hospitalization are
      associated with recurrent ACS.

PMID- 29200152
TI  - Vanishing Bile Duct Syndrome Following Cytomegalovirus Infection in a Child With
      Hodgkin Lymphoma.

PMID- 29200153
TI  - Dengue-associated Hemophagocytic Lymphohistiocytosis: A Rare Complication of a
      Common Infection in Singapore.
AB  - Hemophagocytic lymphohistiocytosis (HLH) can progress rapidly, often leading to
      multisystem organ failure and death. Prompt recognition of the syndrome and
      institution of appropriate treatment are crucial steps in improving the outcome.
      Dengue virus infection is not commonly known to be associated with secondary HLH.
      We present a case of a child with dengue fever who subsequently developed
      classical features of HLH. He was treated successfully with 4 weeks of steroid
      monotherapy instead of the multidrug therapy proposed in the HLH 2004 protocol.
      There was prompt response to the treatment with resolution of clinical and
      biochemical features. He remains in complete remission 3 years from the
      diagnosis.

PMID- 29200154
TI  - Rhinocerebral Mucormycosis With Temporal Artery Thrombosis in an Adolescent
      Following HLA-haploidentical Stem Cell Transplantation.
AB  - Rhinocerebral mucormycosis (RCM) can lead to internal carotid artery thrombosis.
      Here, we report the first case of RCM with temporal artery thrombosis following
      HLA-haploidentical stem cell transplantation in an adolescent presenting with low
      grade fever, right mandibular pain, and right jaw claudication. This case
      suggests that RCM can cause temporal artery thrombosis and should be considered
      as a differential diagnosis in severely immunocompromised patients with maxillary
      sinusitis presenting with jaw claudication.

PMID- 29200155
TI  - A Case of Congenital Dyserythropoeitic Anemia Type IV Caused by E325K Mutation in
      Erythroid Transcription Factor KLF1.
AB  - Congenital dyserythropoetic anemias (CDA) represent a heterogeneous group of
      inherited red cell disorders resulting in ineffective erythropoiesis. Several CDA
      variants have been identified. KLF1 is a transcription factor required for cell
      division in erythroid differentiation and maturation, and the switch from fetal
      to adult hemoglobin. Mutations in KLF1 gene can result in a wide range of
      phenotypes. This case illustrates the E325K mutation in KLF1 presenting with
      severe anemia in infancy, persistently elevated fetal hemoglobin, and progressive
      improvement with age. This case of CDA because of KLF1 mutation highlights the
      common features and expected disease course of CDA type IV.

PMID- 29200156
TI  - Sustained Response to Targeted Therapy in a Patient With Disseminated Anaplastic
      Pleomorphic Xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytoma is a rare brain tumor with unique high frequency of
      BRAF V600E mutation which is plausible for targeted therapy. The anaplastic
      variant has generally worse prognosis. We present an adolescent patient with a
      disseminated relapse of anaplastic pleomorphic xanthoastrocytoma following
      surgery, radiotherapy, and chemotherapy. She had a dramatic and prolonged
      response to a BRAF inhibitor (Dabrafinib) and later to addition of a MEK
      inhibitor (Trametinib) on tumor progression. With minimal side effects and a good
      quality of life, the patient is alive more than 2 years after initiation of
      targeted therapy. This experience confirms the potential role of targeted
      treatments in high-grade BRAF-mutated brain tumors.

PMID- 29200157
TI  - An Infant With Unusually High Unconjugated Hyperbilirubinemia Due to Coexistence
      of Hereditary Spherocytosis and Gilbert Syndrome.
AB  - Hereditary spherocytosis is the most frequent congenital hemolytic anemia and is
      characterized with variable degree of anemia, jaundice, and splenomegaly. In the
      case of severe hyperbilirubinemia out of proportion with hemolysis, other causes
      of hyperbilirubinemia must be considered. Gilbert syndrome (GS) is an autosomal
      dominant disorder characterized with intermittent hyperbilirubinemia without any
      other sign and symptom of liver disease as a result of reduced activity of
      uridine diphosphate-glucuronyl transferase 1A1. The calculated rate of
      coexistence of these 2 diseases is 15 to 35/million births. Here we present a 21
      month-old girl with hereditary spherocytosis diagnosed at the age of 40 days with
      hyperbilirubinemia out of proportion of hemolysis which led to diagnosis of GS.
      Thereby, the diagnosis of GS should be considered in unexplained unconjugated
      hyperbilirubinemia in different age groups, including infants and toddlers.

PMID- 29200158
TI  - Cardiac Toxicity After Craniospinal Irradiation: A Late Effect That May be
      Eliminated With Proton Therapy.
AB  - BACKGROUND: Craniospinal irradiation (CSI) is commonly required for pediatric
      patients with central nervous system malignancies. Traditionally, CSI is given
      using x-rays to deliver radiation to the brain and spine, exposing normal
      anterior structures, including heart, to unnecessary radiation. OBSERVATIONS: We
      present a patient treated with x-ray CSI for medulloblastoma with spinal
      metastasis (3600 cGy CSI with focal boost to 5000 cGy), who subsequently
      developed significant cardiac toxicity, likely related to radiation exposure.
      CONCLUSIONS: Spinal irradiation can cause significant cardiac risk due to exit
      dose through anterior structures. This toxicity may be avoided with proton
      therapy, which eliminates visceral exit dose.

PMID- 29200159
TI  - Posterior Reversible Encephalopathy Syndrome: Risk Factors and Impact on the
      Outcome in Children With Acute Lymphoblastic Leukemia Treated With Nordic
      Protocols.
AB  - Posterior reversible encephalopathy syndrome (PRES) in children with acute
      lymphoblastic leukemia has been increasingly recognized as a clinicoradiological
      entity. Our aim was to describe the incidence of PRES in pediatric patients with
      ALL, identify its risk factors, and examine its prognostic importance. For this
      research, we conducted a systematic, retrospective review of the patient records
      in a population-based series of children with acute lymphoblastic leukemia
      (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5%
      (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during
      induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval
      [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days
      of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent
      risk factors for PRES. One-third of the patients developed epilepsy. Relapses
      occurred significantly more often in those patients with PRES (P=0.001), which
      was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%
      91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a
      significant early complication of therapy in ALL, and was associated with a
      poorer prognosis and significant neurological morbidity.

PMID- 29200160
TI  - Glucose Homeostasis and Effect of Chelation on beta Cell Function in Children
      With beta-Thalassemia Major.
AB  - OBJECTIVE: To assess the prevalence of impaired glucose tolerance in beta
      thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS:
      Sixty-seven subjects with beta-thalassemia major, aged 1 to 20 years, were
      enrolled in our prospective cohort. Clinical details were recorded. Baseline oral
      glucose tolerance test, serum insulin, C peptide, and insulin resistance were
      measured. The biochemical profile was repeated after 6 months. RESULTS: The mean
      age of subjects was 7.43+/-4.48 years. Eight (11.9%) subjects had impaired
      fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject
      had diabetes at baseline. Subjects with abnormal glucose profile had longer
      disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68;
      P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5;
      P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than
      normoglycemic subjects. Insulin resistance and serum ferritin showed significant
      increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone
      alone significantly improved glucose homeostasis on follow-up than those on
      desferrioxamine or combination therapy of desferrioxamine and deferiprone
      (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin
      adversely affects glucose homeostasis in thalassemic children. Deferiprone was
      the most effective chelator to improve glucose homeostasis in chronically
      transfused thalassemics.

PMID- 29200161
TI  - Noninvasive Measurement of Hemoglobin Using Spectrophotometry: Is it Useful for
      the Critically Ill Child?
AB  - This study compared the accuracy of noninvasively measuring hemoglobin using
      spectrophotometry (SpHb) with a pulse CO-oximeter and laboratory hemoglobin (Hb)
      measurements. A total of 345 critically ill children were included prospectively.
      Age, sex, and factors influencing the reliabilityof SpHb such as SpO2, heart
      rate, perfusion index (PI), and vasoactive inotropic score were recorded. SpHb
      measurements were recorded during the blood draw and compared with the Hb
      measurement. Thirteen patients (low PI in 9 patients and no available Hb in 4
      patients) were excluded and 332 children were eligible for final analysis. The
      mean Hb was 8.71+/-1.49 g/dL (range, 5.9 to 12 g/dL) and the mean SpHb level was
      9.55+/-1.53 g/dL (range, 6 to 14.2 g/dL). The SpHb bias was 0.84+/-0.86,with the
      limits of agreement ranging from -2.5 to 0.9 g/dL. The difference between Hb and
      SpHb was >1.5 g/dL for only 47 patients. Of these, 24 patients had laboratory Hb
      levels <7 g/dL. There was a weak positive correlation between differences and PI
      (r=0.349; P= 0.032). The pulse CO-oximeter is a promising tool for measuring SpHb
      and monitoring critically ill children. However, PI may affect these results.
      Additional studies investigating the reliability of the trend of continuous SpHb
      values compared with simultaneously measured laboratory Hb values in the same
      patient are warranted.

PMID- 29200162
TI  - Study of NOTCH1 and FBXW7 Mutations and Its Prognostic Significance in South
      Indian T-Cell Acute Lymphoblastic Leukemia.
AB  - NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream
      target genes play crucial roles in the molecular pathogenesis of T-cell acute
      lymphoblastic leukemia (T-ALL). In the present study, NOTCH1 and FBXW7 mutations
      were studied in 25 primary T-ALL samples. All 34 exons of NOTCH1 and hotspot
      exons (exon 9 and exon 10) of FBXW7 were polymerase chain reaction amplified and
      sequenced for mutations. Our results showed that 13/25 (52%) were NOTCH1-mutated,
      of which 11 patients (44%) showed mutation in the hotspot exons. Four patients
      (16%) had mutations in non-hotspot exons of NOTCH1. Notably, 2 T-ALL patients
      (8%) harbored mutations in both hotspot and non-hotspot exons of NOTCH1, whereas
      2 patients (8%) had mutations in the hotspot exons of FBXW7. In all, 7 mutations
      were identified which were not previously reported. The real-time polymerase
      chain reaction study in 15 patients revealed that increased expression of
      activated NOTCH1 was found in NOTCH1/FBXW7 hotspot exon-mutated cases. In
      addition, NOTCH1/FBXW7-mutated patients had showed upregulated HES1, c-MYC,
      NOTCH3 gene expression. When survival analysis was performed including samples
      (n=50) from our previous study, an early treatment response and better survival
      was observed in NOTCH1/FBXW7 hotspot-mutated patients. Our study suggests that
      NOTCH1/FBXW7 hotspot-mutated T-ALL cases had better response to ALL BFM-95
      protocol.

PMID- 29200163
TI  - Therapy-related Acute Myeloid Leukemia After the Treatment of Primary Solid
      Cancer in Children: A Single-center Experience.
AB  - Therapy-related acute myeloid leukemia (t-AML) has a dismal prognosis and is one
      of the most frequent second malignant neoplasms which could be encountered by
      pediatric oncologists. Between October 2000 and September 2016, 16 patients who
      had primary solid tumors were diagnosed with t-AML at the Seoul National
      University Children's Hospital. The median patient age at the time of diagnosis
      of their primary solid tumors was 9.6 years (range, 0.1 to 15.4 y), and that of t
      AML was 14.0 years (range, 4.7 to 23.9 y). The median latency period from the end
      of the primary tumor treatment to the initial diagnosis of t-AML was 29 months
      (range, 6 to 130 mo). Twelve patients achieved complete remission. Of them, only
      7 patients underwent hematopoietic stem cell transplantation (HSCT). The 3-year
      overall survival (OS) rates and event-free survival rates were 33.7+/-12.2% and
      26.9+/-11.5% respectively. The patients who underwent HSCT showed favorable 5
      year OS rates (57.1+/-18.7%), whereas the 5-year OS rates of those who did not
      undergo HSCT was 0%. This study demonstrates that an achievement of complete
      remission and a subsequent HSCT can be the optimal solution for the treatment of
      t-AML, and this strategy showed acceptable outcomes.

PMID- 29200164
TI  - Neuropilin-1/CD304 Expression by Flow Cytometry in Pediatric Precursor B-Acute
      Lymphoblastic Leukemia: A Minimal Residual Disease and Potential Prognostic
      Marker.
AB  - Flow cytometry (FCM) is used for quantification of minimal residual disease (MRD)
      in acute lymphoblastic leukemia (ALL) through discriminating leukemic B
      lymphoblasts from normal B-cell precursor counterparts "hematogones." Neuropilin
      1 (NRP-1)/CD304 is a vascular endothelial growth factor receptor implicated in
      the progression of hematological malignancies. We evaluated NRP-1/CD304 as MRD
      and prognostic marker in pediatric precursor B-ALL using FCM. Seventy children
      with precursor B-ALL and 40 control children were enrolled. CD304 percentage and
      fluorescence intensity were significantly higher in precursor B-ALL at diagnosis
      compared with controls. In total, 28 of 70 (40%) precursor B-ALL patients at
      diagnosis were CD304 (group A), whereas 42/70 (60%) patients were CD304 (group
      B). Group A showed higher incidence of lymphadenopathy and TEL-AML1 fusion gene
      than group B. CD304 was reevaluated in group A patients at day 28 postinduction
      chemotherapy which revealed 12/28 (42.9%) patients with persistent CD304
      expression (MRD; group A1) and 16/28 (57.1%) patients who turned CD304 (MRD;
      group A2). At diagnosis, group A1 showed lower incidence of TEL-AML1 fusion gene
      and higher risk stratification than group A2. NRP-1/CD304 expression by FCM is
      efficient in discriminating leukemic B-lymphoblasts from hematogones, a stable
      leukemia-associated phenotype for MRD monitoring, and a putative poor prognostic
      marker in pediatric precursor B-ALL.

PMID- 29200165
TI  - Programmed Death Ligand 1 Expression in Classical Hodgkin Lymphoma in Pediatric
      Patients.

PMID- 29200166
TI  - Ataxia Telangiectasia and Cancer Predisposition: Challenges in Management.
AB  - Immune dysregulation and predisposition to malignancies are critical
      comorbidities in children affected with ataxia telangiectasia. In addition, these
      children exhibit increased toxicity to conventional cancer therapy and dose
      reductions have been proposed to prevent life threatening adverse effects. These
      modifications to the treatment regimen may result in suboptimal outcomes for
      these patients. Our report of 3 children with ataxia telangiectasia and cancer
      highlight the immense challenges in the management of these children, underlining
      the need for the development of novel, biological agents with reduced acute and
      long-term side effects in the treatment of cancers in these children.

PMID- 29200167
TI  - A Severe Case of Murine Typhus Presenting With Anemia and Severe
      Thrombocytopenia.
AB  - We discuss a child with severe thrombocytopenia and mild anemia admitted to the
      Hematology service who quickly deteriorated to a life-threatening state. However,
      once rickettsial disease was considered in the differential diagnosis and empiric
      doxycycline begun, she quickly and fully recovered. A diagnostic panel, including
      Rickettsia typhi serology, confirmed the diagnosis of murine typhus but this
      occurred weeks after she had recovered. Given the potential severity of
      rickettsial diseases and the ease of modern travel across geographic borders,
      hematology-oncology providers everywhere must consider rickettsial diseases in
      their differential diagnosis of critically ill children and begin empiric therapy
      with doxycycline promptly.

PMID- 29200168
TI  - Spontaneous Regression in a Patient With Infantile Fibrosarcoma.
AB  - Infantile fibrosarcoma usually presents as a rapidly growing mass on the
      extremities or trunk. We describe spontaneous regression in a 5-month-old female
      infant with biopsy proven, molecularly confirmed, right leg infantile
      fibrosarcoma currently at 26 months of age with no signs of local recurrence.
      Previously reported cases of spontaneous regression are reviewed, suggesting a
      benign clinical course in some cases. Although evidence for spontaneous
      regression is anecdotal in this rare tumor type, physicians should weigh the
      risks and benefits of surgery and chemotherapy against watchful waiting.

PMID- 29200169
TI  - Sinus Histiocytosis With Massive Lymphadenopathy (Rosai Dorfman Disease):
      Diagnostic and Treatment Modalities for this Rare Entity Revisited.
AB  - Rosai-Dorfman disease, also known as sinus histiocytosis with massive
      lymphadenopathy is a rare non-Langerhans' cell histiocytic disease resulting from
      the proliferation and accumulation of sinus histiocytes within lymph nodes.
      Extranodal involvement frequently occurs, which increases the morbidity and
      mortality of the disease. There is no clear consensus with regard to the most
      effective diagnostic and treatment modalities. This report will focus on the
      diagnostic imaging, treatment, and outcomes for 3 cases of Rosai-Dorfman disease.
      Imaging has typically utilized computed tomography (CT)/magnetic resonance
      imaging to detect extranodal involvement. However, the addition of
      fluorodeoxyglucose positron emission tomography/CT scans has shown value in
      identifying lesions unidentified or ambiguous on other modalities.
      Fluorodeoxyglucose positron emission tomography/CT detected disease involvement
      in 2 instances either not reported or not felt to be significant on correlative
      CT imaging. Areas of involvement included the stomach/liver in case 1, and the
      paranasal sinus in case 3. In addition, previously utilized chemotherapy regimens
      have not consistently displayed regression of the disease, which lends credence
      to the pursuit of more successful treatment. Notably, Clofarabine has shown
      promise in its use against histiocytic disorders. Our study concluded that
      Clofarabine demonstrates the ability to decrease lesion size and should be
      considered as an effective chemotherapeutic treatment method.

PMID- 29200170
TI  - Terson Syndrome Before Induction Chemotherapy for Acute Lymphoblastic Leukemia.
AB  - A previously healthy 2-year-old female infant presented with pancytopenia and was
      diagnosed with acute lymphoblastic leukemia. Before the initiation of treatment,
      she developed symptoms concerning for increased intracranial pressure. Head
      imaging revealed left parietal hemorrhage, in addition to a right vitreous
      hemorrhage, which was confirmed on ophthalmology examination later. Terson
      syndrome, in which intraocular hemorrhage is associated with intracranial
      hemorrhage, is more commonly reported in adults, although ocular manifestations
      of leukemia have been reported at presentation and are typically asymptomatic.

PMID- 29200171
TI  - Reduced Neutrophil Elastase Activity and Neutrophil Extracellular Traps in
      Pediatric Acute Myeloid Leukemia May Increase the Rate of Infections.
AB  - Data on the production of neutrophil extracellular traps (NETs) in leukemia
      patients are scant. Phagocytosis, hydrogen peroxide, neutrophil elastase and
      myeloperoxidase enzymatic activity as well as NETs formation were studied in 10
      pediatric acute lymphoblastic leukemia and 7 pediatric acute myeloid leukemia
      (AML) patients after induction chemotherapy. Median neutrophil elastase activity
      and NETs formation were lower in AML versus acute lymphoblastic leukemia (41% vs.
      90%, P=0.005 and 51% vs. 94%, P=0.008, respectively). AML patients had more
      episodes of febrile neutropenia during the first 2 blocks of treatment (100% vs.
      40%, P=0.011) and a trend for more invasive bacterial and fungal infections.

PMID- 29200172
TI  - A Rare Case of Chronic Active Epstein-Barr Virus (EBV) Infection Accompanied by
      the Infiltration of EBV-infected CD8+ T Cells into the Muscle.
AB  - We describe a rare case of chronic active Epstein-Barr virus (CAEBV) infection,
      with infiltration of the skeletal muscle. A 19-year-old woman with swollen
      cervical lymph nodes and a fever was referred to our hospital. Swelling of the
      trapezium muscle and elevation of creatinine kinase level were observed. Biopsy
      results of the brachialis muscle revealed infiltration of Epstein-Barr virus
      (EBV)-encoded RNA-positive CD8 T lymphocytes. The EBV virus load in the
      peripheral blood was high, and EBV monoclonality was determined by Southern blot
      analysis. Owing to the rarity of CAEBV with skeletal muscle infiltration, this
      case alerts physicians to the potential diagnostic pitfalls of CAEBV.

PMID- 29200174
TI  - Predictability of Supine Radiographs for Determining In-Brace Correction for
      Adolescent Idiopathic Scoliosis.
AB  - STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To assess whether
      flexibility as revealed by the supine radiograph, predicts in-brace curve
      correction. SUMMARY OF BACKGROUND DATA: Currently there is no consensus regarding
      a standard method to assess curve flexibility and immediate brace effectiveness
      in treating adolescent idiopathic scoliosis (AIS). Brace fabrication methods may
      be variable but ideally it should achieve maximal curve correction. Curve
      flexibility governs the degree of curve correction in-brace and hence dynamic
      radiographs are commonly performed prior to brace fitting. METHODS: This was a
      radiographic analysis of AIS patients treated with underarm bracing. Correlation
      of pre-brace, supine, and immediate in-brace Cobb angles was performed.
      Relationship with possible contributing factors including age, sex, body height,
      weight, age at menarche and Risser staging was studied. Major and minor curves
      were compared independently for correlation but the regression model was
      constructed based on the major curve only. RESULTS: From 105 patients with mean
      age of 12.2 +/- 1.2 years at brace fitting, supine Cobb angle measurement has
      significant correlation with immediate in-brace Cobb angle (r = 0.740).
      Univariate analyses showed no significant relationship with age, weight, height,
      date of menarche, Risser stage or pre-brace Cobb angle. Our regression model (in
      brace Cobb angle = 0.809 * supine Cobb angle) had good fit of the data.
      CONCLUSION: Supine radiograph predictably determines the flexibility of the
      scoliotic curve to brace treatment. It can be used as a guideline to determine
      the amount of correction achievable with brace-wear. The effectiveness of the
      brace is dependent on the inherent flexibility of the curve rather than its size
      or type. LEVEL OF EVIDENCE: 3.

PMID- 29200175
TI  - How Do We Move Beyond Regression to the Mean?: Improving Health and Health Care.

PMID- 29200173
TI  - Medical Malpractice Claims Following Incidental Durotomy Due to Spinal Surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Analyze medical malpractice
      verdicts and settlements associated with incidental durotomy. SUMMARY OF
      BACKGROUND DATA: Incidental durotomy is a common complication of spine surgery.
      Although most intraoperative dural tears are repaired without sequelae,
      persistent Cerebrospinal Fluid leak, infection, or neurological injury can yield
      adverse outcomes. The medicolegal implications of incidental durotomy are poorly
      understood. METHODS: Three separate, large legal databases were queried for cases
      involving incidental durotomy. Case, plaintiff, procedure, and outcome
      characteristics were analyzed. RESULTS: In total, 48 dural tear-related medical
      malpractice cases were analyzed. Most cases (56.3%) resulted in a ruling in favor
      of the defendant physician. Most cases alleged neurological deficits (86.7%). A
      large majority of cases without neurological sequelae had an outcome in favor of
      the defendant (83.3%). For cases involving a payment, the average amount was
      $2,757,298 in 2016 adjusted dollars. Additional surgery was required in 56.3% of
      cases, a delay in diagnosis/treatment of durotomy was present in 43.8%, and
      alleged improper durotomy repair was present in 22.9%. A favorable outcome for
      the plaintiff was more likely in cases with versus without alleged delay in
      diagnosis/treatment (61.9% vs. 29.6%, P = 0.025) and improper durotomy repair
      technique (72.7% vs. 35.1%, P = 0.040). Repeat surgery was not associated with
      favorable outcome for the plaintiff (42.8% cases with reoperation vs. 38.1%
      without, P = 0.486). CONCLUSION: This analysis of durotomy-associated closed
      malpractice claims after spine surgery is the largest yet conducted. Durotomy
      cannot always be considered an entirely benign event, and these findings have
      several direct implications for clinicians: late-presenting or dehiscent durotomy
      may be associated with adverse outcomes and subsequent risk of litigation, timely
      reoperation in the event of durotomy-related complications may not increase
      surgeon liability, and spine surgeons should be prepared to defend their choice
      of durotomy repair technique, should dehiscence occur. LEVEL OF EVIDENCE: 3.

PMID- 29200176
TI  - Anatomical Study of a Novel Iliosacral Screw Placement for Sacrum-Pelvis in Adult
      Via Computed Tomography Reconstruction.
AB  - STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: To investigate the
      feasibility and safety of a novel iliosacral screw placement for sacrum-pelvis in
      adult pelvis by computed tomography (CT) reconstruction. SUMMARY OF BACKGROUND
      DATA: The optimal technique of spino-pelvic fixation is still being developed and
      redefined. However, neither the relevant anatomic parameters nor the potential
      spinal canal involvement for a novel iliosacral screw placement have been clearly
      analyzed. METHODS: A total of 60 adults with normal pelvis, with the age ranging
      from 24 to 79 years old, were included in this study. Based on three-dimensional
      (3D) CT reconstruction of each pelvis, virtual iliosacral screw channel was
      identified bilaterally, the trajectory of which was characterized with the
      optimal width and length from the ilium to the sacrum. The virtual iliosacral
      screw channel that holding the greatest width and length of osseous channel was
      measured by rotating the 3D pelvis. Measurements of the determined channel on
      either side included iliosacral-screw-related and connector-related parameters.
      RESULTS: There was a virtual iliosacral screw channel passing through the ilium,
      the iliosacral joint and then into the sacrum on either side of each pelvis. The
      caudal angle, convergent angle, and maximal length were 16.3 +/- 3.0 degrees ,
      61.3 +/- 5.9 degrees , 97.0 +/- 5.6 mm in male, respectively. In female, they
      were 16.4 +/- 3.9 degrees , 63.0 +/- 5.5 degrees  and 96.2 +/- 6.0 mm,
      respectively. The ideal direction of the connector was from posteromedial to
      anterolateral. The cephalad angle, divergent angle, and embedding depth of the
      connector were 28.0 +/- 5.7 degrees , 28.7 +/- 5.9 degrees  and 19.0 +/- 2.9 mm
      in male, respectively. In female, they were 26.7 +/- 6.1 degrees , 27.0 +/- 5.5
      degrees  and 16.4 +/- 2.6 mm, respectively. CONCLUSION: It is safe and feasible
      to place the iliosacral screw when performing this novel instrumentation.
      Preoperative CT imaging and 3D reconstructions may help to determine the correct
      entry point and the trajectory of iliosacral screw. LEVEL OF EVIDENCE: 5.

PMID- 29200177
TI  - Effect of Body Mass on Oxygenation and Intra-Abdominal Pressure When Using a
      Jackson Surgical Table in the Prone Position During Lumbar Surgery.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To test the hypothesis
      that different types of surgical frame and the patient's body mass index (BMI)
      can affect pulmonary compliance, intra-abdominal pressure (IAP), and oxygenation.
      SUMMARY OF BACKGROUND DATA: The oxygenation index (PaO2/FiO2) and IAP are known
      to be associated with BMI when patients are in the supine position. However,
      there are few reports on the correlation between BMI, the oxygenation index, and
      IAP in the prone position, especially when a Jackson surgical table is used.
      METHODS: Thirty-seven adult patients were divided into two groups according to
      BMI: normal-weight patients (n = 19, BMI: 18.5-24.9 kg m) and overweight patients
      (n = 18, BMI >= 25 kg m). After the induction of general anesthesia, patients
      were turned to the prone position onto either a Jackson surgical table (Mizuho
      OSI) or a general surgical table (MAQUET; foam pad, China). The patient's IAP,
      peak airway pressure, pulmonary dynamic compliance (Cdyn), and oxygenation index
      were recorded. RESULTS: In overweight patients, there was a greater increase in
      peak airway pressure and a greater decrease in Cdyn observed when a general
      surgical table was used compared with the Jackson surgical table. When the
      Jackson surgical table was used, there was a greater increase in the oxygenation
      index and a greater decrease in IAP. There was a significant negative correlation
      between the oxygenation index and BMI and a significant positive correlation
      between IAP and BMI in the prone position. CONCLUSION: Turning patients from the
      supine to the prone position during anesthesia results in an increase in the
      oxygenation index and a decrease in IAP. Both of these factors are dependent upon
      the type of surgical frame used and the patient's BMI. The reduction in IAP was
      particularly significant when a Jackson surgical table was used for overweight
      patients. LEVEL OF EVIDENCE: 4.

PMID- 29200178
TI  - Induction of chronic migraine phenotypes in a rat model after environmental
      irritant exposure.
AB  - Air pollution is linked to increased emergency department visits for headache and
      migraine patients frequently cite chemicals or odors as headache triggers, but
      the association between air pollutants and headache is not well understood. We
      previously reported that chronic environmental irritant exposure sensitizes the
      trigeminovascular system response to nasal administration of environmental
      irritants. Here, we examine whether chronic environmental irritant exposure
      induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a
      transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by
      inhalation for 4 days before meningeal blood flow measurements, periorbital
      cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos
      expression in trigeminal nucleus caudalis was compared in animals exposed to room
      air or acrolein. Spontaneous behavior and olfactory discrimination was examined
      in open-field testing. Acrolein inhalation exposure produced long-lasting
      potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized
      cutaneous responses to mechanical stimulation. C-Fos expression in response to
      touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein
      compared with room air. Spontaneous activity in an open-field and scent
      preference behavior was different in acrolein-exposed compared with room air
      exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood
      flow changes in response to TRPA1 or transient receptor potential vanilloid
      receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine
      treatment, attenuated the enhanced blood flow responses observed after acrolein
      inhalation exposures. Environmental irritant exposure yields an animal model of
      chronic migraine in which to study mechanisms for enhanced headache
      susceptibility after chemical exposure.

PMID- 29200179
TI  - Structural and functional abnormalities of the insular cortex in trigeminal
      neuralgia: a multimodal magnetic resonance imaging analysis.
AB  - Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by
      intense, lancinating attacks of facial pain. Increasing evidence suggests that TN
      is accompanied by abnormalities in brain morphology, white matter microstructure,
      and function. However, whether these abnormalities are linked or reflect
      independent etiologies remains unknown. Using multimodal magnetic resonance
      imaging data of 20 patients with TN and 21 healthy controls, we investigated
      cortical gyrification abnormalities, their relationships with abnormalities of
      the underlying white matter microstructure and gray matter morphology, as well as
      their functional significance in TN. Compared with controls, patients with TN
      showed significant local gyrification index (LGI) reductions predominantly in the
      left insular cortex, which were negatively correlated with pain intensity. In
      this cluster, patients with TN had concurrent cortical thickness reductions but
      unaltered cortical surface area. Meanwhile, LGI of this cluster was not
      correlated with overlying cortical thickness or surface area but was positively
      correlated with the fractional anisotropy of 2 nearby white matter clusters,
      suggesting that insular LGI reductions may be primarily driven by microstructural
      abnormalities of the underlying white matter tracts, rather than by abnormalities
      in cortical thickness and surface area. In addition, patients with TN exhibited
      increased insula functional connectivity to the left posterior cingulate cortex
      and thalamus, which was positively correlated with disease duration. These
      findings provide new evidence for the involvement of insular abnormalities in the
      pathophysiology of TN.

PMID- 29200180
TI  - Procedural pain and oral glucose in preterm neonates: brain development and sex
      specific effects.
AB  - Our objectives were to determine whether procedural pain and glucose exposure are
      associated with altered structural and functional brain development differently
      in preterm males and females, and neurodevelopment at 18-month corrected age.
      Fifty-one very preterm neonates (22 males; median [interquartile range]
      gestational age 27.6 [2.0] weeks) underwent 3 serial scans including T1-weighted
      and resting-state functional magnetic resonance imaging (MRI) at median
      postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total
      brain volumes were segmented. Functional resting-state MRI data were extracted
      from the independent-components maps. Pain was operationalized as the total
      number of neonatal intensive care unit-administered invasive procedures.
      Neurodevelopmental outcomes at 18-month corrected age were assessed with the
      Bayley Scales of Infant Development, second edition. Generalized estimating
      equations assessed the association of pain and glucose exposure with brain
      structural and functional development. More invasive procedures were
      independently associated with slower growth of thalamic (P < 0.001), basal
      ganglia (P = 0.028), and total brain volumes (P = 0.001), particularly in
      females. Similar relationships were observed between glucose exposure and brain
      volumes. Functional connectivity between thalamus and sensorimotor cortices was
      negatively associated with number of invasive procedures. Greater procedural pain
      and higher glucose exposure were related to poorer neurodevelopmental outcomes.
      These findings suggest that structural and functional brain development is
      vulnerable to procedural pain. Glucose used for analgesia does not appear to
      mitigate the adverse impact of pain on brain development. The vulnerability of
      brain development in females towards early pain is distinct from other neonatal
      morbidities. The link between pain and glucose with neurodevelopment suggests
      that these factors have long-lasting impact.

PMID- 29200182
TI  - Invasive Haemophilus Influenzae Type B Infections in Children with Cancer in the
      Era of Infant HIB Immunization Programs (1991-2014): A Report From the Canadian
      Immunization Monitoring Program Active.
AB  - We studied the epidemiology of Haemophilus influenzae type b infections among
      children with cancer admitted to Canadian pediatric hospitals. From 1991 to 2014,
      13 cases among children with cancer were identified through active surveillance.
      Average age was 6.7 years. Six of 7 cases eligible for infant immunization were
      age-appropriately immunized (vaccine failures). Children with cancer may benefit
      from booster Hib immunization.

PMID- 29200181
TI  - Estimating minimally important differences for the PROMIS pain interference
      scales: results from 3 randomized clinical trials.
AB  - Minimally important difference (MID) refers to the smallest meaningful difference
      that carries implications for patient care. Minimally important differences are
      necessary to help interpret patient-reported pain outcomes in research and
      clinical practice. The PROMIS pain interference scales were validated across
      diverse samples; however, more information about their MIDs could improve their
      interpretability. The purpose of this study was to estimate MIDs for 4 fixed
      length PROMIS pain interference scales, including the 6-item Pain Short Form and
      the 4-, 6-, and 8-item pain interference scales used in the PROMIS profile
      instruments. Data were analyzed from 3 randomized controlled trials (N = 759).
      The 3 samples, respectively, consisted of patients with chronic low back pain (n
      = 261), chronic back pain or hip/knee osteoarthritis pain (n = 240), and a
      history of stroke (n = 258). For each sample, anchor- and distribution-based
      approaches were used to estimate MIDs. Standard error of measurement and effect
      sizes were used as distribution-based MID estimates. Anchor-based MID estimates
      were established by mapping PROMIS pain interference scores onto established
      anchor measures, including the Brief Pain Inventory, and retrospective and
      prospective global ratings of change. The distribution- and anchor-based MID
      estimates showed convergence. For the pain samples, MID estimates ranged from 2
      to 3 T-score points. For the nonpain sample, MID estimates ranged from 3.5 to 4.5
      T-score points. The MID estimates were comparable across the 4 fixed-length
      scales. These MIDs can be used to evaluate treatment effects in research and
      clinical care and to calculate estimates for powering clinical trials.

PMID- 29200183
TI  - Beyond Prevention of Vertical HIV Transmission - Improving Outcomes of HIV
      Uninfected Infants Born to Mothers with HIV Infection.

PMID- 29200185
TI  - Early Vaccine-type Pneumococcal Acute Otitis Media Does not Predispose to
      Subsequent Otitis When Compared With Early Acute Otitis Media Due to Other
      Bacterial Etiology.
AB  - BACKGROUND: Prevention of acute otitis media (AOM), and especially recurrence and
      biofilm formation, by pneumococcal conjugate vaccines has been hypothesized to be
      due to prevention of early episodes triggering the vicious cycle. We tested the
      specific role of vaccine-type pneumococcal AOM in this hypothesis. METHODS: In
      the phase III randomized, double-blind Finnish otitis media Vaccine Trial
      conducted in 1995-1999, children received pneumococcal conjugate vaccine 7 or
      hepatitis B vaccine as control at 2, 4, 6, and 12 months of age and were followed
      for AOM. Myringotomy with middle ear fluid aspiration was performed in AOM, and
      samples were cultured. We compared control-vaccinated children with confirmed
      vaccine-type or 6A-AOM with those with AOM due to other confirmed etiology within
      2-6 months of age (early AOM) and followed for subsequent AOM from 6-24 months of
      age. RESULTS: Eight hundred thirty-one children were enrolled in the Finnish
      otitis media control arm. Before 6 months of age, 34 children experienced vaccine
      type-AOM, and 40 children experienced AOM of other bacterial etiology. The
      subsequent AOM incidences were 1.9 (95% CI, 1.5-2.4) and 2.1 (1.7-2.5) in these
      subgroups, respectively. However, the subsequent incidences were lower if no
      bacteria were detected at AOM (1.5, 1.2-1.8) or if there was no early AOM (1.1,
      1.1-1.2). CONCLUSIONS: Early vaccine-type AOM was not associated with a higher
      risk of subsequent AOM compared with AOM due to other confirmed bacterial
      etiology. These data do not support any specific role of vaccine-type
      pneumococcus in the hypothesis.

PMID- 29200184
TI  - Structural Neuroimaging and Neuropsychologic Signatures in Children With
      Vertically Acquired HIV.
AB  - BACKGROUND: Children with vertically acquired HIV exhibit persistent cognitive
      impairments, yet the corresponding neuroimaging signature of vertical infection
      remains unclear. METHODS: Fifty healthy control children and 51 vertically
      infected children were included in the study. The HIV-infected group consisted of
      survivors who had not received antiretroviral therapy at birth. The HIV-infected
      group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm.
      Most (71%) of the HIV-infected children were on antiretroviral therapy for a
      median of 34 months (range: 33-42) with HIV RNA <40 copies/mL in 89% of the
      sample. The HIV-uninfected group averaged 10.6 (2.6) years of age. Magnetic
      resonance imaging was acquired to determine volumes of the caudate, putamen,
      thalamus, pallidum, hippocampus, nucleus accumbens, total white matter, total
      gray matter and cortical gray matter. Correlational analyses examined the degree
      of shared variance between brain volumes and both cognitive performances and
      laboratory markers of disease activity (T cells and plasma viral load). RESULTS:
      HIV-infected children exhibited larger volumes of the caudate, nucleus accumbens,
      total gray matter and cortical gray matter when compared with the controls.
      Volumetric differences were predominately evident in children under 12 years of
      age. HIV-infected children performed worse than controls on most neuropsychologic
      tests, though neither cognitive performances nor laboratory markers corresponded
      to brain volumes in the HIV-infected children. CONCLUSIONS: Outcomes of the
      present study suggest abnormal brain maturation among HIV-infected pediatric
      survivors. Longitudinal studies of brain integrity and related resilience factors
      are needed to determine the impact of neuroimaging abnormalities on psychosocial
      function in pediatric HIV.

PMID- 29200186
TI  - Potentially Traumatic Events and Job Satisfaction: A Prospective Population-Based
      Comparative Study.
AB  - OBJECTIVE: The aim of this study was to examine the effects of potentially
      traumatic events (PTEs), posttraumatic stress symptoms (PTSS), and coping self
      efficacy (CSE) on post-event job satisfaction. METHODS: Repeated analysis of
      variance (ANOVA) was used to assess differences in the course of job satisfaction
      during 1 year between population-based samples of affected and nonaffected
      workers. Multivariate regression analyses were conducted with pre-event health,
      job satisfaction and insecurity, and postevent PTSS and CSE as predictors.
      RESULTS: About 16% of the affected workers had probable PTSD. The course of job
      satisfaction between affected (n = 123) and nonaffected workers (n = 644) did not
      differ significantly. PTSS and CSE did not independently predict post-event
      satisfaction, in contrast to pre-event job satisfaction. CONCLUSION: Findings
      suggest that when needed social support is provided, concerns about the negative
      effects of potentially traumatic events on job satisfaction could be somewhat
      relaxed.

PMID- 29200187
TI  - The Combined Effect of Long Working Hours and Low Job Control on Self-Rated
      Health: An Interaction Analysis.
AB  - OBJECTIVES: The aim of this study was to investigate the combined effects of long
      working hours and low job control on self-rated health. METHODS: We analyzed
      employees' data obtained from the third Korean Working Conditions Survey (KWCS).
      Multiple survey logistic analysis and postestimation commands were employed to
      estimate the relative excess risk due to interaction (RERI). RESULTS: The odds
      ratio (OR) for poor self-rated health was 1.24 [95% confidence interval (95% CI):
      1.13 to 1.35] for long working hours, 1.04 (95% CI: 0.97 to 1.13) for low job
      control, and 1.47 (95% CI: 1.33 to 1.62) for both long working hours and low job
      control. The RERI was 0.18 (95% CI: 0.02 to 0.34). CONCLUSION: These results
      imply that low job control may increase the negative influence of long working
      hours on self-rated health.

PMID- 29200188
TI  - The Measurable Benefits of a Workplace Wellness Program in Canada: Results After
      One Year.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of an employee
      wellness program in Canada. METHODS: A comprehensive program including web-based
      lifestyle challenges was evaluated with annual health screenings. RESULTS: Among
      730 eligible employees, 688 (94%) registered for the program, 571 (78%) completed
      a health screening at baseline, and 314 (43%) at 1 year. Most (66%) employees
      tracked their activity for more than 6 weeks. At 1-year follow-up, there were
      significant clinical improvements in systolic blood pressure -3.4 mm Hg, and
      reductions in poor sleep quality (33% to 28%), high emotional stress (21% to
      15%), and fatigue (11% to 6%). A positive dose-response was noted where the
      greatest improvements were observed among those who participated the most.
      CONCLUSION: The program had high employee engagement. After 1 year, the benefits
      included clinically important improvements in physical and mental health.

PMID- 29200189
TI  - Medical Surveillance for Hazardous Drugs: A Qualitative Assessment of Current
      Practices.
AB  - OBJECTIVE: The National Institute for Occupational Safety and Health recommends
      that institutions establish a medical surveillance program for workers who handle
      hazardous drugs. Our aim was to investigate current practices with occupational
      medicine practice (OMP) national leaders. METHODS: A series of qualitative
      telephone interviews were conducted with 11 OMP national leaders from medical
      centers in 10 states. Interviews were recorded, transcribed, and coded using a
      directed content analysis. Codes were organized into themes. RESULTS: All
      respondents were board-certified physicians in medical center OMP. Interviews up
      to 45 minutes found three themes: policy interpretation, benefits and barriers to
      surveillance, and potential respondent-generated solutions. Three of 10 medical
      centers provided medical surveillance. CONCLUSIONS: Medical surveillance for
      hazardous drugs is infrequent, and consensus is lacking regarding standard
      practices. Further work is needed to minimize risk to health care workers.

PMID- 29200191
TI  - Determination of Thresholds of Radioactive Iodine Uptake Response With Clinical
      Exposure to Perchlorate: A Pooled Analysis.
AB  - OBJECTIVE: To conduct a more robust examination of perchlorate exposure on iodide
      uptake inhibition (IUI) using pooled data from four clinical studies of
      perchlorate exposure. METHODS: To establish a response threshold for IUI, data
      were analyzed using segmented linear regression and benchmark dose (BMD)
      analysis. RESULTS: Segmented linear regression applied to data for 69 subjects
      representing nine doses identified a breakpoint corresponding to a change in the
      slope of the dose-response relationship of 3.0 mg/d perchlorate. The estimated
      BMD for a 20% decrease in iodine uptake was 2.3 mg/d, with a lower 95% confidence
      interval limit of 1.6 mg/d. CONCLUSIONS: A threshold dose for IUI from
      perchlorate exposure of 1.6 to 3.0 mg/d (0.021 to 0.038 mg/kg d) was estimated
      using two modeling approaches. These estimates are slightly higher than the
      lowest observed effect level of 0.02 mg/kg d from the Greer Study.

PMID- 29200190
TI  - Libby Amphibole Disease: Pulmonary Function and CT Abnormalities in Vermiculite
      Miners.
AB  - OBJECTIVE: This article describes radiologic and pulmonary function findings
      among miners exposed to Libby amphibole. Computed tomography (CT) permits the
      detection of the characteristic thin, lamellar pleural thickening (LPT). METHODS:
      Individuals who worked at the mine for a minimum of 6 months had chest CT and
      pulmonary function tests. RESULTS: Pleural thickening was noted in 223 (87%) of
      the 256 miners, parenchymal abnormalities in 49 (19%). LPT, found in 151 (68%),
      was associated with low values of forced vital capacity and diffusion capacity
      and significantly lower values in all pulmonary function tests when associated
      with parenchymal abnormalities. CONCLUSION: Eighty-seven percent of miners
      exposed to Libby Amphibole had pleural abnormalities on CT. LPT alone, and more
      so with parenchymal abnormalities, resulted in decreased pulmonary function. The
      importance of this easily missed LPT is demonstrated by its high frequency and
      significant functional effects.

PMID- 29200192
TI  - The Associations of Multimorbidity With Health-Related Productivity Loss in a
      Large and Diverse Public Sector Setting: A Cross-Sectional Survey.
AB  - OBJECTIVE: To evaluate absenteeism, presenteeism, and total lost productive time
      (LPT) associated with multimorbidity. METHODS: Cross-sectional data from 3228
      state-government employees from Tasmania were collected in 2013. The validated
      measures of absenteeism, presenteeism, and LPT were obtained from employees' self
      reported data over a 28-day period. Analyses were stratified by sex. Negative
      binomial models were used to estimate the associations between multimorbidity and
      LPT. RESULTS: The average health-related total LPT was 1.2 (standard deviation
      [SD] = 2.4) and 1.7 (SD = 3.5) days for men and women with multimorbidity,
      respectively. Women (rate ratio [RR] = 2.9, 95% confidence interval [CI] 1.8 to
      4.9) and men (RR = 4.4, 95%CI 3.0 to 6.2) with 4+ chronic conditions were
      significantly more likely to report LPT compared with those without any chronic
      conditions. CONCLUSION: We found multimorbidity is of concern within the
      workforce, with a positive association of multimorbidity and LPT observed, and
      significant differences in LPT between men and women reporting multimorbidity.

PMID- 29200193
TI  - Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus
      antibodies.
AB  - The antibody repertoire of Bos taurus is characterized by a subset of variable
      heavy (VH) chain regions with ultralong third complementarity determining regions
      (CDR3) which, compared to other species, can provide a potent response to
      challenging antigens like HIV env. These unusual CDR3 can range to over seventy
      highly diverse amino acids in length and form unique beta-ribbon 'stalk' and
      disulfide bonded 'knob' structures, far from the typical antigen binding site.
      The genetic components and processes for forming these unusual cattle antibody VH
      CDR3 are not well understood. Here we analyze sequences of Bos taurus antibody VH
      domains and find that the subset with ultralong CDR3 exclusively uses a single
      variable gene, IGHV1-7 (VHBUL) rearranged to the longest diversity gene, IGHD8-2.
      An eight nucleotide duplication at the 3' end of IGHV1-7 encodes a longer V
      region producing an extended F beta-strand that contributes to the stalk in a
      rearranged CDR3. A low amino acid variability was observed in CDR1 and CDR2,
      suggesting that antigen binding for this subset most likely only depends on the
      CDR3. Importantly a novel, potentially AID mediated, deletional diversification
      mechanism of the B. taurus VH ultralong CDR3 knob was discovered, in which
      interior codons of the IGHD8-2 region are removed while maintaining integral
      structural components of the knob and descending strand of the stalk in place.
      These deletions serve to further diversify cysteine positions, and thus disulfide
      bonded loops. Hence, both germline and somatic genetic factors and processes
      appear to be involved in diversification of this structurally unusual cattle VH
      ultralong CDR3 repertoire.Cellular and Molecular Immunology advance online
      publication, 4 December 2017; doi:10.1038/cmi.2017.117.

PMID- 29200194
TI  - Recent advances in regulatory T cells induced by B cells.

PMID- 29200195
TI  - Sub-nanometre channels embedded in two-dimensional materials.
AB  - Two-dimensional (2D) materials are among the most promising candidates for next
      generation electronics due to their atomic thinness, allowing for flexible
      transparent electronics and ultimate length scaling. Thus far, atomically thin p
      n junctions, metal-semiconductor contacts, and metal-insulator barriers have been
      demonstrated. Although 2D materials achieve the thinnest possible devices,
      precise nanoscale control over the lateral dimensions is also necessary. Here, we
      report the direct synthesis of sub-nanometre-wide one-dimensional (1D) MoS2
      channels embedded within WSe2 monolayers, using a dislocation-catalysed approach.
      The 1D channels have edges free of misfit dislocations and dangling bonds,
      forming a coherent interface with the embedding 2D matrix. Periodic dislocation
      arrays produce 2D superlattices of coherent MoS2 1D channels in WSe2. Using
      molecular dynamics simulations, we have identified other combinations of 2D
      materials where 1D channels can also be formed. The electronic band structure of
      these 1D channels offers the promise of carrier confinement in a direct-gap
      material and the charge separation needed to access the ultimate length scales
      necessary for future electronic applications.

PMID- 29200196
TI  - Topological order and thermal equilibrium in polariton condensates.
AB  - The Berezinskii-Kosterlitz-Thouless phase transition from a disordered to a quasi
      ordered state, mediated by the proliferation of topological defects in two
      dimensions, governs seemingly remote physical systems ranging from liquid helium,
      ultracold atoms and superconducting thin films to ensembles of spins. Here we
      observe such a transition in a short-lived gas of exciton-polaritons, bosonic
      light-matter particles in semiconductor microcavities. The observed quasi-ordered
      phase, characteristic for an equilibrium two-dimensional bosonic gas, with a
      decay of coherence in both spatial and temporal domains with the same algebraic
      exponent, is reproduced with numerical solutions of stochastic dynamics, proving
      that the mechanism of pairing of the topological defects (vortices) is
      responsible for the transition to the algebraic order. This is made possible
      thanks to long polariton lifetimes in high-quality samples and in a reservoir
      free region. Our results show that the joint measurement of coherence both in
      space and time is required to characterize driven-dissipative phase transitions
      and enable the investigation of topological ordering in open systems.

PMID- 29200197
TI  - Control of piezoelectricity in amino acids by supramolecular packing.
AB  - Piezoelectricity, the linear relationship between stress and induced electrical
      charge, has attracted recent interest due to its manifestation in biological
      molecules such as synthetic polypeptides or amino acid crystals, including gamma
      (gamma) glycine. It has also been demonstrated in bone, collagen, elastin and the
      synthetic bone mineral hydroxyapatite. Piezoelectric coefficients exhibited by
      these biological materials are generally low, typically in the range of 0.1-10 pm
      V-1, limiting technological applications. Guided by quantum mechanical
      calculations we have measured a high shear piezoelectricity (178 pm V-1) in the
      amino acid crystal beta (beta) glycine, which is of similar magnitude to barium
      titanate or lead zirconate titanate. Our calculations show that the high
      piezoelectric coefficients originate from an efficient packing of the molecules
      along certain crystallographic planes and directions. The highest predicted
      piezoelectric voltage constant for beta-glycine crystals is 8 V mN-1, which is an
      order of magnitude larger than the voltage generated by any currently used
      ceramic or polymer.

PMID- 29200199
TI  - Programmable full-adder computations in communicating three-dimensional cell
      cultures.
AB  - Synthetic biologists have advanced the design of trigger-inducible gene switches
      and their assembly into input-programmable circuits that enable engineered human
      cells to perform arithmetic calculations reminiscent of electronic circuits. By
      designing a versatile plug-and-play molecular-computation platform, we have
      engineered nine different cell populations with genetic programs, each of which
      encodes a defined computational instruction. When assembled into 3D cultures,
      these engineered cell consortia execute programmable multicellular full-adder
      logics in response to three trigger compounds.

PMID- 29200198
TI  - NetSig: network-based discovery from cancer genomes.
AB  - Methods that integrate molecular network information and tumor genome data could
      complement gene-based statistical tests to identify likely new cancer genes; but
      such approaches are challenging to validate at scale, and their predictive value
      remains unclear. We developed a robust statistic (NetSig) that integrates protein
      interaction networks with data from 4,742 tumor exomes. NetSig can accurately
      classify known driver genes in 60% of tested tumor types and predicts 62 new
      driver candidates. Using a quantitative experimental framework to determine in
      vivo tumorigenic potential in mice, we found that NetSig candidates induce tumors
      at rates that are comparable to those of known oncogenes and are ten-fold higher
      than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates
      in 242 patients with oncogene-negative lung adenocarcinomas, we find that two
      (AKT2 and TFDP2) are significantly amplified. Our study presents a scalable
      integrated computational and experimental workflow to expand discovery from
      cancer genomes.

PMID- 29200200
TI  - Wogonin protects against cisplatin-induced acute kidney injury by targeting RIPK1
      mediated necroptosis.
AB  - Acute kidney injury (AKI), characterized by aggressive inflammatory responses and
      destruction of renal resident cells, can cause abrupt kidney dysfunction. To
      date, effective therapy for AKI is lacking. In this study, we evaluated the
      renoprotective effect of wogonin, an herbal active compound, using a cisplatin
      induced AKI mouse model. In vivo results show that wogonin substantially
      suppressed the increased levels of serum creatinine and blood urea nitrogen (BUN)
      almost to the normal level. Wogonin also attenuated tubular damage, shown by PAS
      staining, electron microscopy and molecular analysis of KIM-1. In addition,
      wogonin suppressed kidney inflammation as indicated by a >60% decrease in
      macrophage infiltration, a >50% reduction in inflammatory cytokine production and
      inhibited NF-kappaB activation in the injured kidney. Mechanistically, molecular
      docking results show that wogonin effectively inhibited RIPK1 by occupying the
      ATP-binding pocket of the enzyme, which is a key regulator of necroptosis.
      Moreover, inhibition of RIPK1, or RIPK3, reversed the protective effects of
      wogonin in cisplatin-treated HK2 cells, indicating wogonin works in a RIPK1/RIPK3
      dependent manner. Surprisingly, wogonin enhanced the anti-proliferative effect of
      cisplatin on human hepatoma HepG2 cells. Thus, our findings suggest wogonin may
      be a renoprotective adjuvant for cisplatin-based anticancer therapy.

PMID- 29200201
TI  - The actions of NME1/NDPK-A and NME2/NDPK-B as protein kinases.
AB  - Nucleoside diphosphate kinases (NDPKs) are multifunctional proteins encoded by
      the nme (non-metastatic cells) genes, also called NM23. NDPKs catalyze the
      transfer of gamma-phosphate from nucleoside triphosphates to nucleoside
      diphosphates by a ping-pong mechanism involving the formation of a high-energy
      phosphohistidine intermediate. Growing evidence shows that NDPKs, particularly
      NDPK-B, can additionally act as a protein histidine kinase. Protein kinases and
      phosphatases that regulate reversible O-phosphorylation of serine, threonine, and
      tyrosine residues have been studied extensively in many organisms. Interestingly,
      other phosphoamino acids histidine, lysine, arginine, aspartate, glutamate, and
      cysteine exist in abundance but remain understudied due to the paucity of
      suitable methods and antibodies. The N-phosphorylation of histidine by histidine
      kinases via the two- or multi-component signaling systems is an important
      mediator in cellular responses in prokaryotes and lower eukaryotes, like yeast,
      fungi, and plants. However, in vertebrates knowledge of phosphohistidine
      signaling has lagged far behind and the identity of the protein kinases and
      protein phosphatases involved is not well established. This article will
      therefore provide an overview of our current knowledge on protein histidine
      phosphorylation particularly the role of nm 23 gene products as protein histidine
      kinases.

PMID- 29200202
TI  - Advances in development of new tools for the study of phosphohistidine.
AB  - Protein phosphorylation is an important post-translational modification that is
      an integral part of cellular function. The O-phosphorylated amino-acid residues,
      such as phosphoserine (pSer), phosphothreonine (pThr) and phosphotyrosine (pTyr),
      have dominated the literature while the acid labile N-linked phosphorylated amino
      acids, such as phosphohistidine (pHis), have largely been historically overlooked
      because of the acidic conditions routinely used in amino-acid detection and
      analysis. This review highlights some misinterpretations that have arisen in the
      existing literature, pinpoints outstanding questions and potential future
      directions to clarify the role of pHis in mammalian signalling systems.
      Particular emphasis is placed on pHis isomerization and the hybrid functionality
      for both pHis and pTyr of the proposed tau-pHis analogue bearing the triazole
      residue.

PMID- 29200203
TI  - miR-200b/c attenuates lipopolysaccharide-induced early pulmonary fibrosis by
      targeting ZEB1/2 via p38 MAPK and TGF-beta/smad3 signaling pathways.
AB  - Pulmonary fibrosis triggered during the early stage of acute respiratory distress
      syndrome (ARDS) contributes to poor prognosis in patients. However, whether
      microRNAs (miRNAs) can serve as therapeutic targets for early pulmonary fibrosis
      during ARDS is still largely unknown. In this study, we evaluated the effects and
      mechanisms of miR-200s and its targets ZEB1/2 in lung tissue. An early pulmonary
      fibrosis mouse model caused by ARDS was established via a lipopolysaccharide
      (LPS) three-hit regimen. Lentiviral packaged miR-200b/c cDNA or ZEB1/2 shRNA was
      intratracheally administered into the lungs of C57BL/6 mice 1 day before an LPS
      injection was administered. In vitro, following a 30-min pretreatment with miR
      200b/c or SB203580/SIS3, RLE-6TN cells were stimulated by LPS or LPS +
      transforming growth factor-beta (TGF-beta) for 24 h. miR-200b/c and E-cadherin
      protein expression declined, whereas ZEB1/2 mRNA and protein and vimentin and
      alpha-smooth muscle actin (alpha-SMA) protein levels gradually increased during
      the development of pulmonary fibrosis. Furthermore, both the overexpression of
      miR-200b/c and the silencing of ZEB1/2 significantly alleviated pulmonary
      inflammation and fibrosis, reduced vimentin and alpha-SMA expression, and
      increased E-cadherin protein levels. In RLE-6TN cells, LPS combined with TGF-beta
      exerts synergistic effects of increasing vimentin and alpha-SMA protein levels,
      increasing p38 and smad3 phosphorylation and reducing E-cadherin protein levels,
      which were reversed by pretreatment with miR-200b/c or SB203580/SIS3. Our
      findings demonstrate that miR-200b/c was downregulated, whereas ZEB1/2 was
      upregulated in the development of LPS-induced early pulmonary fibrosis. miR
      200b/c exerts a protective effect by targeting ZEB1/2, which may be associated
      with the inhibition of p38 MAPK and TGF-beta /smad3 signaling pathways.

PMID- 29200204
TI  - Thyroid hormone inhibits lung fibrosis in mice by improving epithelial
      mitochondrial function.
AB  - Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis
      during stress responses, but its role in lung fibrosis is unknown. Here we found
      that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme
      that activates TH, were higher in lungs from patients with idiopathic pulmonary
      fibrosis than in control individuals and were correlated with disease severity.
      We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung
      fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two
      models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF
      beta1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis.
      After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved
      mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in
      alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in
      Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We
      conclude that the antifibrotic properties of TH are associated with protection of
      alveolar epithelial cells and restoration of mitochondrial function and that TH
      may thus represent a potential therapy for pulmonary fibrosis.

PMID- 29200205
TI  - Amyloid-beta plaques enhance Alzheimer's brain tau-seeded pathologies by
      facilitating neuritic plaque tau aggregation.
AB  - Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta)
      plaques and intracellular tau inclusions. However, the exact mechanistic link
      between these two AD lesions remains enigmatic. Through injection of human AD
      brain-derived pathological tau (AD-tau) into Abeta plaque-bearing mouse models
      that do not overexpress tau, we recapitulated the formation of three major types
      of AD-relevant tau pathologies: tau aggregates in dystrophic neurites surrounding
      Abeta plaques (NP tau), AD-like neurofibrillary tangles (NFTs) and neuropil
      threads (NTs). These distinct tau pathologies have different temporal onsets and
      functional consequences on neural activity and behavior. Notably, we found that
      Abeta plaques created a unique environment that facilitated the rapid
      amplification of proteopathic AD-tau seeds into large tau aggregates, initially
      appearing as NP tau, which was followed by the formation and spread of NFTs and
      NTs, likely through secondary seeding events. Our study provides insights into a
      new multistep mechanism underlying Abeta plaque-associated tau pathogenesis.

PMID- 29200206
TI  - Discovery and characterization of highly potent and selective allosteric USP7
      inhibitors.
AB  - Given the importance of ubiquitin-specific protease 7 (USP7) in oncogenic
      pathways, identification of USP7 inhibitors has attracted considerable interest.
      Despite substantial efforts, however, the development of validated deubiquitinase
      (DUB) inhibitors that exhibit drug-like properties and a well-defined mechanism
      of action has proven particularly challenging. In this article, we describe the
      identification, optimization and detailed characterization of highly potent (IC50
      < 10 nM), selective USP7 inhibitors together with their less active, enantiomeric
      counterparts. We also disclose, for the first time, co-crystal structures of a
      human DUB enzyme complexed with small-molecule inhibitors, which reveal a
      previously undisclosed allosteric binding site. Finally, we report the
      identification of cancer cell lines hypersensitive to USP7 inhibition (EC50 < 30
      nM) and demonstrate equal or superior activity in these cell models compared to
      clinically relevant MDM2 antagonists. Overall, these findings demonstrate the
      tractability and druggability of DUBs, and provide important tools for additional
      target validation studies.

PMID- 29200208
TI  - [Balances, decrees, previsions, provocations].

PMID- 29200207
TI  - Human antibody-based chemically induced dimerizers for cell therapeutic
      applications.
AB  - Chemically induced dimerizers (CIDs) have emerged as one of the most powerful
      tools for artificially regulating signaling pathways in cells; however, currently
      available CID systems lack the properties desired for use in regulating cellular
      therapies. Here, we report the development of human antibody-based chemically
      induced dimerizers (AbCIDs) from known small-molecule-protein complexes by
      selecting for synthetic antibodies that recognize the chemical epitope created by
      the bound small molecule. We demonstrate this concept by generating three
      antibodies that are highly selective for the BCL-xL-ABT-737 complex compared to
      BCL-xL alone. We show the potential of AbCIDs for application in regulating human
      cell therapies by using them to induce CRISPRa-mediated gene expression and to
      regulate CAR T-cell activation. We believe that the AbCIDs generated in this
      study will find application in regulating cell therapies and that the general
      method of AbCID development may lead to the creation of many new and orthogonal
      CIDs.

PMID- 29200209
TI  - [Nursing sensitive outcomes and staffing: a review on healthcare associated
      infection].
AB  - : . Nursing sensitive outcomes and staffing: a review on healthcare associated
      infection. INTRODUCTION: Healthcare associated infections (HAI) continue to be an
      unresolved problem in hospital settings. AIM: To assess the relationship between
      nurse staffing and healthcare associated infections in different settings.
      METHODS: From April to May 2015 a review of literature was conducted consulting
      PubMed, CINAHL and Cochrane Library. RESULTS: An increased amount of Registered
      Nurse Hours Per Patient Day (RNHPPD) and nurse-to-patient ratio was associated to
      a decreased occurrence of HAI. In particular an increase of RNHPPD was associated
      to a reduction of postoperative (OR 0.83, IC95% 0.0.70-0.99), and ventilator
      associated pneumonia (OR 0.21, IC95% 0.08-0.53). Even the number of urinary tract
      infections (-34%) and sepsis (OR 0.54, IC95%: 0.31-0.92) decreased significantly.
      The most significant results associated to an increase of HPPD were obtained in
      intensive care units. CONCLUSIONS: The review showed the correlations between
      nurse staffing and the most frequent HAIs. Nursing managers should be aware of
      the adequate nurse-to-patient ratios and skill-mix in order to inform decision
      making and improve the quality and safety of patients care.

PMID- 29200210
TI  - [Prospective assessment of the agreement of instruments for measuring the
      hospital nursing workload: the Swiss Method, the Karnofsky Performance Status
      Scale and the subjective perception of the nurses].
AB  - : . Prospective assessment of the agreement of instruments for measuring the
      hospital nursing workload: the Swiss Method, the Karnofsky Performance Status
      Scale and the subjective perception of the nurses. INTRODUCTION: An emerging need
      of all healthcare organizations is the availability of reliable measures of
      nursing workload and underlines the problem of the choice of reliable criteria
      and scores. AIM: To assess the agreement between Swiss Method (SM), Karnofsky
      Performance Status Scale (K) and Subjective Perception (SP) of nurses in defining
      the nursing workload. METHODS: A prospective observational study was conducted
      throught computerized compilation of the three scales for each patient in 21
      consecutive days, in a large specialized hospital. Nurses were asked to rate the
      average nursing workload in the last 24 hours. The scales were compared through
      Cohen's Kappa across different sets of patients. RESULTS: The data were collected
      for 7.810 patient days on 1.187 patients. At different levels of aggregation
      there was a strong heterogeneity between the care-related profiles and the levels
      of concordance that rarely exceeded the "discreet" level. However a reasonable
      agreement was obtained between K and SP in medical and surgical wards. The formal
      comparison of the three scales makes it impossible to formulate a preferential
      judgment for any of the three. CONCLUSIONS: Measuring phenomena such as workload
      requires reliable instruments targeted for specific contexts and to the aims
      results will be used for. The study directly compared on a hospital
      representative sample the results of the adoption of instruments- expected to be
      eterogeneous- and often used to guide the allocation of human and material
      resources.

PMID- 29200211
TI  - [The bedside handover: the experience of the heart and vascular surgery of Trento
      hospital].
AB  - : . The bedside handover: the experience of the heart and vascular surgery of
      Trento hospital. INTRODUCTION: The bedside handover (BH) increases the patients
      and nurses' satisfaction. AIMS: To describe the implementation of the BH in two
      wards of a large hospital in Trento. METHODS: The BH was initially implemented in
      the morning shift, and then extended to the other shifts. Patients' satisfaction
      was measured by interviewing 13 patients after one and 6 months; nurses
      satisfaction and opinions were collected with focus groups. The BHs were
      monitored by the head nurse and in a sample of BHs the contents and nurses
      behaviors were observed. RESULTS: The patients appreciated the BH and feel more
      involved in their care; the nurses did not report major problems in introducing
      the BH, however, some aspects need improvement such as nurses' introduction to
      the patient and the identification of potential patients problems. Nurses' skill
      in organizing the information increased. The duration of the handover time did
      not increase, however, the two teams need to overlap for 30 minutes. CONCLUSIONS:
      BH can be implemented if an organizational support is guaranteed.

PMID- 29200212
TI  - [A methodological birthday: NHS 1978-2018].

PMID- 29200213
TI  - [The medical use of Cannabis].

PMID- 29200214
TI  - [Skin toxicity of monoclonal antibodies].

PMID- 29200215
TI  - [Handshaking forbidden in hospitals].

PMID- 29200217
TI  - Nonadiabatic rotational states of the hydrogen molecule.
AB  - We present a new computational method for the determination of energy levels in
      four-particle systems like H2, HD, and HeH+ using explicitly correlated
      exponential basis functions and analytic integration formulas. In solving the
      Schrodinger equation, no adiabatic separation of the nuclear and electronic
      degrees of freedom is introduced. We provide formulas for the coupling between
      the rotational and electronic angular momenta, which enable calculations of
      arbitrary rotationally excited energy levels. To illustrate the high numerical
      efficiency of the method, we present the results for various states of the
      hydrogen molecule. The relative accuracy to which we determined the
      nonrelativistic energy reached the level of 10-12-10-13, which corresponds to an
      uncertainty of 10-7-10-8 cm-1.

PMID- 29200218
TI  - Optically controlled reversible protein hydrogels based on photoswitchable
      fluorescent protein Dronpa.
AB  - Exploiting the optically controlled association and dissociation behavior of a
      photoswitchable fluorescent protein, Dronpa145N, here we demonstrate the
      engineering of an optically switchable reversible protein hydrogel using
      Dronpa145N-based protein building blocks. Our results open the possibility to
      optically tune the mechanical, chemical and structural properties of protein
      hydrogels.

PMID- 29200219
TI  - Ordering of lipid membranes altered by boron nitride nanosheets.
AB  - Boron nitride nanosheets are novel promising nanomaterials with a lower
      cytotoxicity than graphene making them a better candidate for biomedical
      applications. However, there is no systematic study on how they interact with
      cell membranes. Here we employed large scale all-atom molecular dynamics
      simulations to provide molecular details of the structure and properties of
      membranes after the insertion of boron nitride nanosheets. Our results reveal
      that the boron nitride nanosheet can extract phospholipids from the lipid
      bilayers and is enveloped by the membrane. Afterwards, the acyl chains of lipid
      molecules re-orient and become more ordered. As a result, a fluid to gel phase
      transition occurs in the 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer.
      Consequently, the bending moduli of the bilayers increase, and the diffusivity of
      the individual lipid molecule decreases. These changes will affect relevant
      cellular activities, such as endocytosis and signal transduction. Our study
      provides novel insights into the biocompatibility and cytotoxicity of boron
      nitride nanosheets, which may facilitate the design of safer nanocarriers,
      antibiotics and other bio-nanotechnology applications.

PMID- 29200220
TI  - A hybrid functional study of native point defects in Cu2SnS3: implications for
      reducing carrier recombination.
AB  - The native point defects in the earth-abundant solar material Cu2SnS3 are studied
      using the hybrid functional. To generate more accurate formation energies of
      defects, the extended Freysoldt, Neugebauer, and Van de Walle (FNV) method is
      used for finite-size corrections in the charged supercell calculations. According
      to the calculated defect energetics, it is found that the usual experimental
      conditions can lead to abundant deep centers that deteriorate solar cell
      performance. To reduce the carrier recombination caused by the deep centers, Sn
      rich and S-poor conditions should be attempted. The present calculations also
      give satisfactory explanations for a recent experimental work on the defect
      levels in Cu2SnS3.

PMID- 29200222
TI  - Passivation of the surface imperfection of TiO2 by using ZIF-8 for efficient
      carrier separation/transfer.
AB  - Photoelectrochemical (PEC) water splitting offers a promising chance for energy
      generation on a global scale. TiO2 is a widely used photoanode material due to
      its superior properties and stability. However, the PEC efficiency of TiO2 is
      usually impeded by the fast recombination of photo-generated electron/hole pairs
      and the poor charge transfer ability that could be improved by band alignment and
      imperfection passivation, respectively. Herein, we first report that ZIF-8 is an
      efficient imperfection passivating layer which acts as a bifunctional cocatalyst
      for transferring/separating electron/hole pairs for improving the
      photo/photoelectrochemical performance. This work provides a new insight to
      investigate the charge interaction mechanism between the interface of TiO2 and
      ZIF-8.

PMID- 29200221
TI  - Highly sensitive and selective detection of Pd2+ ions using a ferrocene-rhodamine
      conjugate triple channel receptor in aqueous medium and living cells.
AB  - Herein, a novel ferrocene-rhodamine receptor conjugated with an allylimine bridge
      was facilely synthesized. This triple channel receptor can selectively and
      sensitively monitor Pd2+ ions through chromogenic, fluorogenic and
      electrochemical assays in aqueous medium with a low detection limit (8.46 * 10-9
      M) and a fast response (<8 min). It can be applied as a fluorescent probe for
      effective survey of Pd2+ ions in living cells. Moreover, a plausible recognition
      mode was proposed and rationalized by theoretical calculations.

PMID- 29200223
TI  - Oxidation catalyst obtained by the immobilization of layered double
      hydroxide/Mn(iii) porphyrin on monodispersed silica spheres.
AB  - Several functional hybrid materials have been reported as immobilized porphyrin
      derivatives in various organic and inorganic host materials (polymers, mineral
      clays, silica, etc.), with potential applications in various fields, such as
      photochemistry, electrochemistry and heterogeneous catalysis. Layered double
      hydroxides (LDHs), commonly known as hydrotalcite-like materials, have also been
      analyzed for use as supports for metallocomplexes. Recently, nanocomposite
      materials with a core-shell structure produced by combining two kinds of
      nanometer-size materials have received considerable attention, since the use of
      these materials is a promising strategy to prevent the aggregation and self
      oxidation of molecules, reducing the catalytic activity. In this study,
      monodispersed hierarchical layered double hydroxides on silica spheres (LDH@SiO2)
      with core-shell structures were developed for metalloporphyrin immobilization and
      the materials were used as the oxidant catalysts of different substrates.

PMID- 29200224
TI  - Controlling the emission in flexibly-linked (N^C^N)platinum dyads.
AB  - The synthesis, spectroscopic and theoretical characterizations of dinuclear
      Pt(ii) complexes where the two chromophoric units are connected though a
      polyether chain via either the central benzene ring of the tridentate ligand dpyb
      (Pt-2), or the phenylacetylide ligand (Pt-3), are described. The spacer, which
      contains four oxyethylene -CH2CH2O- units, is flexible and long enough to allow a
      self-association of the Pt units by folding, as shown by DFT calculations.
      Comparison of the photophysical properties of the dinuclear complex Pt-2 with
      those of the mononuclear complex Pt-1, used as reference, demonstrates the key
      role played by the linker group in the interaction processes. In addition, the
      emission of complex Pt-2 was found to be affected by the temperature, nature of
      the solvent, and cation coordination as evidenced by luminescence and 1H NMR
      studies. The interacting processes are highly dependent on the solvent polarity
      that controls the - extended vs folded - arrangement and, consequently, induces
      solvatochromic shifts. This unique photophysical behavior of Pt-2 allows the
      modulation of the emission from green to deep-red (up to 125 nm) over the visible
      part of the spectrum. By contrast, complex Pt-3 has a high propensity to form a
      red-shifted intense emissive excimer. DFT and TD-DFT investigations of the
      excimers in Pt-2 and Pt-3 consistently show a much stronger interaction in the
      latter complex.

PMID- 29200216
TI  - High performance affinity chromatography and related separation methods for the
      analysis of biological and pharmaceutical agents.
AB  - The last few decades have witnessed the development of many high-performance
      separation methods that use biologically related binding agents. The combination
      of HPLC with these binding agents results in a technique known as high
      performance affinity chromatography (HPAC). This review will discuss the general
      principles of HPAC and related techniques, with an emphasis on their use for the
      analysis of biological compounds and pharmaceutical agents. Various types of
      binding agents for these methods will be considered, including antibodies,
      immunoglobulin-binding proteins, aptamers, enzymes, lectins, transport proteins,
      lipids, and carbohydrates. Formats that will be discussed for these methods range
      from the direct detection of an analyte to indirect detection based on
      chromatographic immunoassays, as well as schemes based on analyte extraction or
      depletion, post-column detection, and multi-column systems. The use of biological
      agents in HPLC for chiral separations will also be considered, along with the use
      of HPAC as a tool to screen or study biological interactions. Various examples
      will be presented to illustrate these approaches and their applications in fields
      such as biochemistry, clinical chemistry, and pharmaceutical research.

PMID- 29200225
TI  - Unveiling the role of ancillary ligands in acceptorless benzyl alcohol
      dehydrogenation and etherification mediated by mesoionic carbene iridium
      complexes.
AB  - We synthesized a set of triazolylidene iridium(iii) complexes [IrCp*(C^N)L]n+
      (Cp* = pentamethylcyclopentadienyl, C^N = C,N-bidentate coordinating pyridyl
      triazolylidene) containing different neutral or anionic ancillary ligands L and
      evaluated their impact on the catalytic activity in alcohol conversion. We
      demonstrate that these ancillary ligands have a strong influence on the catalytic
      selectivity and direct whether the iridium center preferentially catalyzes either
      the dehydrogenation or the dehydration of benzyl alcohol. Ligand exchange
      experiments provide a direct correlation of ligand lability with catalytic
      activity and selectivity. These results underline the relevance of ancillary
      ligands and provide a rational approach to tailor the catalytic activity of the
      iridium center towards aldehyde formation (loss of H2) or etherification
      (elimination of H2O).

PMID- 29200226
TI  - Green synthesis of a new layered aluminium citraconate: crystal structures,
      intercalation behaviour towards H2O and in situ PXRD studies of its
      crystallisation.
AB  - A new Al-based layered MOF [Al2(OH)4(O2C-C3H4-CO2)].nH2O denoted as CAU-15-Cit
      was synthesised under mild aqueous conditions. It exhibits a layered structure
      incorporating infinite chains of edge-sharing AlO6 polyhedra being interconnected
      by citraconate anions to arrange into layers, which are stacked in an AAA fashion
      (citraconic acid = methylmaleic acid = H2Cit, HO2C-C3H4-CO2H). The crystal
      structures of the hydrated and dehydrated MOF were determined ab initio from
      powder X-ray diffraction (PXRD) data. The hydrated form of this compound (n~ 3)
      crystallises in the space group C2/c (a = 7.4074(8), b = 23.006(3), c = 7.0890(4)
      A, beta = 85.024(7) degrees ) and is converted to a triclinic anhydrous form (n =
      0) upon dehydration (a = 7.0010(3), b = 7.5062(8), c = 9.2212(8) A, alpha =
      72.143(7), beta = 88.617(9), gamma = 85.242(8) degrees , space group P1[combining
      macron]) in which the layers are interdigitated with a decreased interlayer
      distance. Physisorption measurements of the anhydrous form indicated no porosity
      towards nitrogen but an uptake of water vapour was measured showing a sigmoidal
      adsorption curve and a capacity of ~24 wt%. This is in good agreement with the
      theoretical capacity for complete intercalation (~25 wt%). Based on the
      temperature dependent PXRD data of the hydrated form, the intercalated water is
      removed at around 100  degrees C and the framework decomposes above 350  degrees
      C. The dehydration process was further compared to the behaviour of the
      structurally related aromatic variant of the MOF based on phthalic acid, denoted
      as CAU-15 [Al2(OH)4(O2C-C6H4-CO2)].nH2O. The crystallisation of CAU-15-Cit was
      investigated by means of in situ PXRD measurements during the synthesis using
      synchrotron radiation at temperatures between 90 and 130  degrees C. Evaluation
      of the kinetics using the Sharp-Hancock method clearly indicated different
      kinetic regimes for the reactions, regardless of the synthesis temperature. At
      lower temperatures the rate limiting step during the initial period is
      nucleation, while this initial reaction stage is kinetically limited by diffusion
      at higher temperatures. The second reaction stage at all temperatures is
      approximately of the first order.

PMID- 29200227
TI  - Animal Model of Brain Aging: Senescence-Accelerated Mouse (SAM).

PMID- 29200228
TI  - Heteromerization of GABAB Receptors: A New Principle for G Protein-Coupled
      Receptors. Satellite Symposium to the 28th Annual Meeting of the Society for
      Neuroscience Los Angeles, CA, November 5-7, 1998.

PMID- 29200229
TI  - CP-101,606: An NR2B-Selective NMDA Receptor Antagonist.

PMID- 29200230
TI  - Application of Gene Knockout Technique to Alcohol Research. Satellite Symposium
      to the 28th Annual Meeting of the Society for Neuroscience. Los Angeles, CA,
      November 7, 1998.

PMID- 29200231
TI  - 1998 Annual Meeting of the Society for Neuroscience: New Drugs Affecting the
      Central Nervous System. Los Angeles, California, November 7-12, 1998.

PMID- 29200233
TI  - The Pharmacology and Mechanism of Action of Zolpidem.

PMID- 29200232
TI  - Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy.

PMID- 29200234
TI  - Neuron-Glial Interactions. The Sixth Annual University of Southern California
      Neuroscience Symposium, Los Angeles, November 6, 1998.

PMID- 29200235
TI  - Glial Cells in Aging and Neurodegeneration. A Satellite Symposium to the 28th
      Annual Meeting of the Society for Neuroscience. Los Angeles, CA, November 7,
      1998.

PMID- 29200236
TI  - Diagnostics of endometriosis by using magnetic resonance imaging.
AB  - Endometriosis affects about 2 to 10% of women in fertile age, It causes pain and
      infertility. In the ovaries, endometrios causes endometriomas. The disease may
      spread into the abdominal cavity and even result in ileus. Deep endometriomas are
      located under the peritoneal surface, typically behind the uterus and in the
      region of uterosacral ligaments. History, clinical examination and transvaginal
      ultrasound scanning usually lead to the diagnosis. Magnetic resonance imaging is
      in particular utilized prior to surgery. It provides a comprehensive view of
      endometriosis lesions in the pelvis, including deep foci.

PMID- 29200237
TI  - Disordered eating behavior in boys of draft age - the population-based MOPO
      study.
AB  - BACKGROUND: Eating disorders in boys are poorly detected in health care. MATERIAL
      AND METHODS: Among 922 boys attending evaluation for military service in Oulu, In
      2013, disordered eating behavior was assessed by the SCOFF and Eating Disorder
      Inventory questionnaires (Drive fir thinness and Bulimia). RESULTS: Disordered
      eating behavior was present in 129 (14%) boys, of whom 57 (44%) were overweight.
      Every fourth overweight by had symptoms of eating disorders, typically constant
      thoughts of weight loss. CONCLUSIONS: Screening of eating disorders should be
      included in medical examinations, especially in overweight boys.

PMID- 29200238
TI  - Entrustable professional activity (EPA) reshapes the practice of specialist
      training.
AB  - In addition to medical expertise, competence-based medical training comprises
      communication and collaboration skills, professionalism, and leadership skills.
      Continuous feedback is essential for learning and development, and feedback only
      from the medical specialist examination taken in the end of training does not
      ensure thorough specialist training. Entrustable professional activity (EPA) is a
      unit of professional practice, defined as tasks or responsibilities typical of
      the specialty. EPA translates competence-based training into manageable and
      meaningful entities and provides tools for the evaluation of medical competence.

PMID- 29200239
TI  - Hypothermia caused by psoriasis.
AB  - Severe psoriasis can lead to erythroderma, which is a widespread inflammatory
      condition of the skin. Erythroderma increases the amount of water evaporating
      from the skin and heat loss. We present a case of severe hypothermia with rectal
      temperature of 29.3  degrees C caused by psoriasis and a septic infection.

PMID- 29200243
TI  - ?

PMID- 29200240
TI  - Endodontic treatment.
AB  - The Finnish guideline on endodontics emphasizes good quality of endodontic
      treatment and coronal seal of the restoration. For prevention of endodontic
      treatment need caries control is essential. For deep carious lesions stepwise
      excavation or partial caries removal are recommended. Partial pulpotomy can be
      used if bleeding can be controlled. The decision for root canal treatment is
      based on prognosis, occlusion and general health of the patient. The use of
      kofferdam is essential in aseptic working.  Chemomechanical preparation with
      NaOCI and root canal filling within 0-2 mm from the apex improve prognosis.
      Healing should be controlled annually up to four years.

PMID- 29200244
TI  - Management of airway obstruction and stridor in pediatric patients [digest].
AB  - Stridor is a result of turbulent air-flow through the trachea from upper airway
      obstruction, and although in children it is often due to croup, it can also be
      caused by noninfectious and/or congenital conditions as well as life-threatening
      etiologies. The history and physical examination guide initial management, which
      includes reduction of airway inflammation, treatment of bacterial infection, and,
      less often, imaging, emergent airway stabilization, or surgical management. This
      issue discusses the most common as well as the life-threatening etiologies of
      acute and chronic stridor and its management in the emergency department. [Points
      & Pearls is a digest of Pediatric Emergency Medicine Practice].

PMID- 29200245
TI  - Management of inflammatory bowel disease flares in the emergency department
      [digest].
AB  - Because of the chronic relapsing nature of inflammatory bowel disease (IBD),
      emergency clinicians frequently manage patients with acute flares and
      complications. IBD patients present with an often-broad range of nonspecific
      signs and symptoms, and it is essential to differentiate a mild flare from a life
      threatening intra-abdominal process. Recognizing extraintestinal manifestations
      and the presence of infection are critical. This issue reviews the literature on
      management of IBD flares in the emergency department, including laboratory
      testing, imaging, and identification of surgical emergencies, emphasizing the
      importance of coordination of care with specialists on treatment plans and
      offering patients resources for ongoing support. [Points & Pearls is a digest of
      Emergency Medicine Practice.].

PMID- 29200246
TI  - EDTORIAL_.
AB  - Why did we prepare this supplement and why it is about interdisciplinary public
      health issues? It is rather difficult question, but with a simple answer.
      Neurology field, neuroendocrinology field and many other areas of medicine are
      actually very important partners for public health professionals. Public health
      promotes and protects the health of people and the communities where they live,
      learn, work and play. While doctors treat people who are sick, those of us
      working in public health try to prevent people from getting sick or injured in
      the first place.

PMID- 29200247
TI  - Review of Utilization of Cardiovascular Medicines by Daily Defined Dose in the
      Czech Republic and Slovak Republic.
AB  - To the Editor, Drug utilization is an important field of drug policy and an
      integral part of public health internationally. This area of research attracts
      increasing interest but the pioneering work was done 50 years ago when the first
      drug consumption report from six European countries for the period of 1966-1967
      showed great differences in drug utilization between population groups (WHO,
      1968). These results gave important stimulus for creation of Anatomical
      Therapeutic Chemical (ATC) classification and technical unit of measurement
      called the Defined Daily Dose (DDD) which is specified as "the assumed average
      maintenance dose per day for a drug used for its main indication in adults" that
      dealt with the objections against traditional units of measurement in drug
      utilization studies (WHO, 2016). The ATC/DDD methodology has in the meantime
      proved its suitability in drug utilization monitoring and research. As mentioned
      previously, consumption of pharmaceuticals is often used as a basis for
      comparison between countries. Based on our professional expertise, we decided to
      analyze the consumption of cardiovascular medicines by DDD in the Czech Republic
      and Slovak Republic within all ATC groups reported to OECD (OECD, 2016a).
      According to OECD indicator results, the Slovak Republic showed in 2014 a higher
      pharmaceutical consumption by DDD in ATC group C (cardiovascular system) compared
      to the Czech Republic (OECD, 2016a).

PMID- 29200248
TI  - Detection of anti-infliximab antibodies in Slovak IBD patients and its costs
      saving effect.
AB  - OBJECTIVE: Management chronic inflammatory bowel disease (IBD) patients is
      associated with diagnosis, targeted treatment and and individual approach. There
      is a group of patients which loss the response to the biologic treatment caused
      by insufficient levels of biologics or positive antibodies against these drugs.
      This study was aimed to determine the prevalence of patients with positive
      antibodies against the biological treatment and the costs saving probabilities of
      the antibodies detection during the treatment. STUDY DESIGN: This retrospective
      study was based on examination of 183 IBD patients' sera (72 with Crohn's disease
      (CD) and 111 ulcerative colitis (UC)) treated with infiliximab. METHODS:
      Circulating serum infliximab concentrations and anti-infliximab antibodies (ATI)
      were quantified by ELISA methods. Costs associated with the treatment were
      analysed from the data of General Health Insurance Company, Slovakia. RESULTS:
      The average infliximab concentrations in groups of CD were 2.9 ug/mL, 38.9% of
      samples had a concentration <=1 ug/mL. Group with UC had average infliximab
      levels of 3.19 ug/mL, 32.4% bellow <=1 ug/mL. Positive ATI levels were detected
      in 52 patients, in 28 patients with CD (38.8%) and 24 patients with UC (21.6%).
      The average values of the antibodies were 387.75 U/ml in CD and 391.94 U/ml in UC
      group. More than 28% IBD patients were positive for ATI. After application of the
      results to the database of all IBD patients, finishing of the treatment with ATI
      could lead (after considering the ATI quantification costs) to possible annual
      savings of more than ?2 million in Slovakian health-care system. CONCLUSIONS:
      Monitoring of infliximab and antibodies against infliximab and anti-TNF-alpha
      biologics may help optimize treatment strategies and costs for biological
      treatment.

PMID- 29200249
TI  - Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in
      the era of increasing antimicrobial resistance: do we have an additional tool for
      antibiotic policy decisions?
AB  - OBJECTIVE: No previous analyses have attempted to determine optimal therapy for
      upper respiratory tract infections on the basis of cost-minimization models and
      the prevalence of antimicrobial resistance among respiratory pathogens in
      Slovakia. This investigation compares macrolides and cephalosporines for
      empirical therapy and look at this new tool from the aspect of potential
      antibiotic policy decision-making process. METHODS: We employed a decision tree
      model to determine the threshold level of macrolides and cephalosporines
      resistance among community respiratory pathogens that would make cephalosporines
      or macrolides cost-minimising. To obtain information on clinical outcomes and
      cost of URTIs, a systematic review of the literature was performed. The cost
      minimization model of upper respiratory tract infections (URTIs) treatment was
      derived from the review of literature and published models. RESULTS: We found
      that the mean cost of empirical treatment with macrolides for an URTIs was ?93.27
      when the percentage of resistant Streptococcus pneumoniae in the community was
      0%; at 5%, the mean cost was ?96.45; at 10%, ?99.63; at 20%, ?105.99, and at 30%,
      ?112.36. Our model demonstrated that when the percentage of macrolide resistant
      Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather
      than macrolides minimizes the treatment cost of URTIs. CONCLUSIONS: Empirical
      macrolide therapy is less expensive than cephalosporines therapy for URTIs unless
      macrolide resistance exceeds 13.8% in the community. Results have important
      antibiotic policy implications, since presented model can be use as an additional
      decision-making tool for new guidelines and reimbursement processes by local
      authorities in the era of continual increase in antibiotic resistance.

PMID- 29200250
TI  - Intraoperative calcitonin stimulation testing in the surgical treatment of C-cell
      disease.
AB  - OBJECTIVE: The prognosis of medullary thyroid carcinoma (MTC), derived from
      parafollicular C-cells, depends on the completeness of the initial surgical
      excision. The C-cells produce calcitonin, a peptide hormone used as a biochemical
      and immunohistochemical tumor marker. The aim of the study was to evaluate an
      individualized approach to patients with C-cell disease, i.e. MTC and C-cell
      hyperplasia (CCH), using the intraoperative calcitonin testing-assisted surgical
      strategy as a predictor of the final outcome. STUDY DESIGN: A unicentre cross
      sectional study. METHODS: From June 2009 to May 2015, thirty one patients with
      MTC/CCH were surgically treated primarily (n=24) or reoperated for persistence of
      the disease (n=7). Depending on the result of intraoperative calcitonin
      stimulation testing (iCST), patients underwent total thyroidectomy with or
      without lymph node dissection. All patients were tested repeatedly in the
      postoperative period (range 1 to 48 months). RESULTS: The iCST was true negative
      in all CCH, and ten out of eleven N0 MTC primarily operated patients, and true
      positive in one N0 patient and six of the seven reoperated patients. The test was
      false negative in two patients preoperatively evaluated as N+, one primarily
      operated and one reoperated, respectively. CONCLUSION: The results encourage the
      use of an individualised approach on patients with MTC/CCH, e.g. to be less
      radical surgically in cases of negative iCST, and to be more radical in those
      patients with persistent increase of serum calcitonin. The absence of post
      stimulation calcitonin elevation in iCST seems to be a good prognosis indicator
      in patients with an early-stage C-cell disease, but longer follow-up is needed.

PMID- 29200251
TI  - Misdiagnosing of malaria as RTI decreased after introduction of RDTs in rural
      areas of Kenya.
AB  - BACKGROUND: Clinical presentation of malaria is highly variable and can be
      mistaken for number of other diseases, including respiratory tract diseases,
      which are associated with significant morbidity and mortality. However,
      presumptive management of fever as malaria can result in significant
      overdiagnosis, even in high-risk areas. Quality microscopy services for the
      diagnosis of malaria are not widely available in rural areas of Sub-Saharan
      Africa as well as in substandard conditions of low-income settings and the
      accuracy of microscopy is usually poor. MATERIAL AND METHODS: The aim of the
      study was to determine how introduction of RDTs influenced diagnostics of malaria
      in high risk area of Eldoret, Kenya. Documentation of every patient was screened
      for data of current disease and diagnostic tools used. In patients with suspected
      malaria, either microscopy, or RDT or both were done to confirm the diagnosis.
      RESULTS: Initially, incidence of malaria was very high, about 50-70% of all
      visits in OPD due to any infectious condition. In 2010, when rapid diagnostic
      tests became available in Eldoret, decrease in incidence of malaria from 49%
      (2010) to 29% (2011) and further to 5.3% (2016) was noted. At the same time,
      increased incidence of upper and especially lower respiratory tract infections
      was noted. CONCLUSION: Results suggest that upper and lower respiratory tract
      infections were formerly diagnosed and treated as malaria. Other contributing
      factors, such as improvement of infrastructure and malaria preventive and
      treatment programs also play a role in decreasing malaria incidence in rural
      areas of Kenya, however, RDTs play a key role in proper diagnostics of malaria.

PMID- 29200252
TI  - Fetal adrenal gland enlargement - prenatal and postnatal management.
AB  - BACKGROUND: The enlargement of suprarenal gland is related to preterm birth and
      the birth weight. The ultrasound measurement of fetal adrenal gland volume may
      identify women at risk for impending preterm birth. The aim of our study was to
      investigate the newborns in the region of western Slovakia followed up due to
      suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal
      gland enlargment, postnatal managment and treatment and interventions. The
      newborns with congenital adrenal hyperplasia were excluded. METHODS: We have
      analyzed 6 years of medical records of all cases from the western Slovakia region
      of suprarenal gland enlargement encountered to 1st Pediatric Department,
      Children's University Hospital Bratislava Republic in the time period of January
      2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by
      ultrasound examination performed on the 4th postnatal day as an overall screening
      test. Newborns with positive laboratory screening on congenital adrenal
      hyperplasia (CAH) were excluded from our study. We analyzed the origin of
      surarenal gland enlargement, gestation week on the due date, the birth weight and
      other comorbidities and genetic pathologies in newborns with the enlarged
      suprarenal glands. RESULTS: There were 6 newborns followed up due to suprarenal
      gland enlargement. All of the patients had diagnosed the adrenal haemorrhage.
      Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of
      the adrenal enlargements were benign with no need of other medical or surgical
      intervention. None of the newborn patients had other genetic abnormalities,
      mineral or hormonal imbalances, problems with arterial pressure or haemodynamic
      instability. All of the patients underwent at least 5 prenatal ultrasound tests
      and at least 2 postnatal ultrasound measurements. The avarage birth weight was
      3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47
      centimeter to 53 cm).The average gestation week (gw) on due date was 39 gw. 85%
      from the patients were born on 40 gw, 15% on 39 gw. CONCLUSION: We didn't confirm
      the relation between the suprarenal gland enlargement and the preterm birth (<=
      34 weeks' gestation). In the period of 6 years we didn't find a newborn patient
      with the prenatal diagnosis of suprarenal gland enlargement. The adrenal gland
      enlargement didn't have a relation with the low gestation birth, weight, length
      or the preterm birth.

PMID- 29200253
TI  - The role of implementation and communication of MANTRA Water, sanitation and
      hygiene program in improving public health in Odisha state (India).
AB  - BACKGROUND: Provision of safe drinking water is the main strategy to reduce the
      number of water-borne diseases. The Government of India has declared its
      commitment towards achieving Sustainable Development Goals and universal
      sanitation coverage in the country by the year 2022. Indian NGO Gram Vikas offers
      a solution to this task through its flagship WASH program MANTRA. It focuses on
      water and sanitation as an entry point for integrated village development.
      METHODS: The case study from Haradango village (Odisha state, India) investigates
      the effectiveness of MANTRA program by identifying key principles of this Gram
      Vikas' flagship programme and by analysing an impact of its implemenation and
      communication on public health of Haradango villagers. Based on field research
      key principles were identified (100 % inclusion, Gender equity, Social equity,
      Cost-sharing, Sustainability). RESULTS: Thanks to the application of the
      principles, reduction of nearly 80 % of water borne diseases was recorded and
      diarrhea incidence has been less than 2 %. CONCLUSIONS: Gram Vikas' community
      driven development approach towards improvement of public health and sustainable
      rural development can be labeled as successful model for local, as well as
      national projects. Information, education and communication activities need to
      persist in order to overcome the cultural practice of open defecation within
      communities..

PMID- 29200254
TI  - "Lack of knowledge is no excuse" HIV positive patient with progressive multifocal
      leukoencephalopathy. Case report from Kenya.
AB  - Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating
      disease that affects the central nervous system, which has high morbidity and
      mortality and no effective, targeted therapies are available. According to the
      data from developing countries, it affects about 3 to 5% patients who are HIV
      positive. We present a case of a 27-year-old patient, who got infected with the
      HIV virus from his mother. The patient had poor compliance to the therapy since
      its initiation. Due to poor compliance and immunological and virological failure
      of the first line ARVs, the patient developed PML. Despite confirmed diagnosis of
      PML and change of the regimen to the second line ARVs, due to progression of the
      condition, he sought care of an unknown physician, who prescribed therapy with
      azathioprine 150 mg twice daily, which the patient used for more than 2 weeks.
      Despite immediate virological suppression, the condition significantly worsened,
      until the patient developed paraparesis, postural tremor, head tremor, severe
      dysarthria; he was not able to walk, eat or express himself. The major roadblocks
      to diagnosis of PML include poor access to health care in general, as well as
      poor knowledge of the rare condition among the health care professionals. Therapy
      with azathioprine has been proved to be associated with the development of PML.
      Thus, in resource limited settings, there is an urgent need for improved access
      to health care and imaging and laboratory diagnostic means, which would decrease
      the economic and social burden of severe conditions, such as PML.

PMID- 29200255
TI  - Few-Layer WSe2 Schottky Junction-Based Photovoltaic Devices through Site
      Selective Dual Doping.
AB  - Ultrathin sheets of two-dimensional (2D) materials like transition metal
      dichalcogenides have attracted strong attention as components of high-performance
      light-harvesting devices. Here, we report the implementation of Schottky junction
      based photovoltaic devices through site-selective surface doping of few-layer
      WSe2 in lateral contact configuration. Specifically, whereas the drain region is
      covered by a strong molecular p-type dopant (NDP-9) to achieve an Ohmic contact,
      the source region is coated with an Al2O3 layer, which causes local n-type doping
      and correspondingly an increase of the Schottky barrier at the contact. By
      scanning photocurrent microscopy using green laser light, it could be confirmed
      that photocurent generation is restricted to the region around the source
      contact. The local photoinduced charge separation is associated with a
      photoresponsivity of up to 20 mA W-1 and an external quantum efficiency of up to
      1.3%. The demonstrated device concept should be easily transferrable to other van
      der Waals 2D materials.

PMID- 29200256
TI  - A Novel Type of Battery-Supercapacitor Hybrid Device with Highly Switchable Dual
      Performances Based on a Carbon Skeleton/Mg2Ni Free-Standing Hydrogen Storage
      Electrode.
AB  - The sharp proliferation of high power electronics and electrical vehicles has
      promoted growing demands for power sources with both high energy and power
      densities. Under these circumstances, battery-supercapacitor hybrid devices are
      attracting considerable attention as they combine the advantages of both
      batteries and supercapacitors. Here, a novel type of hybrid device based on a
      carbon skeleton/Mg2Ni free-standing electrode without the traditional nickel foam
      current collector is reported, which has been designed and fabricated through a
      dispersing-freeze-drying method by employing reduced graphene oxide (rGO) and
      multiwalled carbon nanotubes (MWCNTs) as a hybrid skeleton. As a result, the
      Mg2Ni alloy is able to deliver a high discharge capacity of 644 mAh g-1 and, more
      importantly, a high cycling stability with a retention of over 78% after 50
      charge/discharge cycles have been achieved, which exceeds almost all the results
      ever reported on the Mg2Ni alloy. Simultaneously, the electrode could also
      exhibit excellent supercapacitor performances including high specific capacities
      (296 F g-1) and outstanding cycling stability (100% retention after 100 cycles).
      Moreover, the hybrid device can switch between battery and supercapacitor modes
      immediately as needed during application. These features make the C
      skeleton/alloy electrode a highly promising candidate for battery-supercapacitor
      hybrid devices with high power/energy density and favorable cycling stability.

PMID- 29200257
TI  - Hexagonal VS2 Anchored MWCNTs: First Approach to Design Flexible Solid-State
      Symmetric Supercapacitor Device.
AB  - Transition metal chalcogenides (TMCs) embedded with a carbon network are gaining
      much attention because of their high power capability, which can be easily
      integrated to portable electronic devices. Facile chemical route has been
      explored to synthesize hexagonal structured VS2 nanoparticles onto multiwalled
      carbon nanotubes (MWCNTs) matrix. Such surface-modified VS2/MWCNTs electrode has
      boosted the electrochemical performance to reach high capacitance to 830 F/g and
      excellent stability to 95.9% over 10 000 cycles. Designed flexible solid-state
      symmetric supercapacitor device (FSSD) with a wide voltage window of 1.6 V
      exhibited maximum gain in specific capacitance value of 182 F/g at scan rate of 2
      mV/s along with specific energy of 42 Wh/kg and a superb stability of 93.2% over
      5000 cycles. As a practical approach, FSSD has lightened up "VNIT" panel
      consisting of 21 red LEDs.

PMID- 29200258
TI  - Roll-to-Roll Laser-Printed Graphene-Graphitic Carbon Electrodes for High
      Performance Supercapacitors.
AB  - Carbon electrodes including graphene and thin graphite films have been utilized
      for various energy and sensor applications, where the patterning of electrodes is
      essentially included. Laser scribing in a DVD writer and inkjet printing were
      used to pattern the graphene-like materials, but the size and speed of
      fabrication has been limited for practical applications. In this work, we devise
      a simple strategy to use conventional laser-printer toner materials as precursors
      for graphitic carbon electrodes. The toner was laser-printed on metal foils,
      followed by thermal annealing in hydrogen environment, finally resulting in the
      patterned thin graphitic carbon or graphene electrodes for supercapacitors. The
      electrochemical cells made of the graphene-graphitic carbon electrodes show
      remarkably higher energy and power performance compared to conventional
      supercapacitors. Furthermore, considering the simplicity and scalability of roll
      to-roll (R2R) electrode patterning processes, the proposed method would enable
      cheaper and larger-scale synthesis and patterning of graphene-graphitic carbon
      electrodes for various energy applications in the future.

PMID- 29200259
TI  - Extremely Low Operating Current Resistive Memory Based on Exfoliated 2D
      Perovskite Single Crystals for Neuromorphic Computing.
AB  - Extremely low energy consumption neuromorphic computing is required to achieve
      massively parallel information processing on par with the human brain. To achieve
      this goal, resistive memories based on materials with ionic transport and
      extremely low operating current are required. Extremely low operating current
      allows for low power operation by minimizing the program, erase, and read
      currents. However, materials currently used in resistive memories, such as
      defective HfOx, AlOx, TaOx, etc., cannot suppress electronic transport (i.e.,
      leakage current) while allowing good ionic transport. Here, we show that 2D
      Ruddlesden-Popper phase hybrid lead bromide perovskite single crystals are
      promising materials for low operating current nanodevice applications because of
      their mixed electronic and ionic transport and ease of fabrication. Ionic
      transport in the exfoliated 2D perovskite layer is evident via the migration of
      bromide ions. Filaments with a diameter of approximately 20 nm are visualized,
      and resistive memories with extremely low program current down to 10 pA are
      achieved, a value at least 1 order of magnitude lower than conventional
      materials. The ionic migration and diffusion as an artificial synapse is realized
      in the 2D layered perovskites at the pA level, which can enable extremely low
      energy neuromorphic computing.

PMID- 29200260
TI  - Tuning the Distance of Rattle-Shaped IONP@Shell-in-Shell Nanoparticles for
      Magnetically-Targeted Photothermal Therapy in the Second Near-Infrared Window.
AB  - Construction of multifunctional nanoparticles (NPs) with near-infrared (NIR)
      plasmonic responses is considered a versatile and multifaceted platform for
      several biomedical applications. Herein, a double layer of Au/Ag alloy on the
      surface of truncated octahedral iron oxide NPs (IONPs) was prepared and the
      distance between the layers was controlled to exhibit broad and strong NIR
      absorption. The rattle-shaped IONP@shell-in-shell nanostructure showed light
      response to the NIR biological window from 650 to 1300 nm for photothermal
      therapy (PTT) and magnetic guidance for hyperthermia and magnetic resonance
      imaging (MRI) diagnosis. Exposing the aqueous solution of IONP@shell-in-shell to
      a 1064 nm diode laser, its heat conversion efficiency was ~28.3%. The in vitro
      cell viability at a gold concentration of 100 ppm was ~85%, and decreased to ~16%
      when the cells were treated with the NIR irradiation and magnetic attraction. T2
      weighted MRI images showed a clear accumulation of IONP@shell-in-shell at the
      tumor site with magnetic attraction. In vivo luminescence tumor images explained
      that the IONP@shell-in-shell could reduce the U87MG-luc2 cancer cell
      proliferation in mice with the NIR irradiation and magnetic attraction. These
      results indicate the IONP@shell-in-shell as a promising nanomedicine for PTT,
      magnetic targeting, and magnetic resonance imaging (MRI).

PMID- 29200261
TI  - Cross-Linked Graphitic Carbon Nitride with Photonic Crystal Structure for
      Efficient Visible-Light-Driven Photocatalysis.
AB  - Highly cross-linked graphitic carbon nitride has been prepared by a thermal
      copolymerization of dicyanodiamide with tetramethylammonium salts. The cross
      linking can be evidenced by (i) increased C/N ratio without new carbon species,
      (ii) decreased specific surface area, and (iii) Tyndall effect after dissolution
      in concentrated sulfuric acid. The cross-linked graphitic carbon nitride with
      photonic crystal structure has highly efficient photocatalytic activity for water
      splitting under visible light due to the synergistic enhancement by the greatly
      suppressed photoluminescence, red-shifted absorption edges, strong inner
      reflections, and effective PCs stop band overlaps. It exhibits an enhanced
      photodegradation kinetic of methyl orange and a high visible-light-driven
      hydrogen-evolution rate of 166.9 MUmol h-1 (25 times higher than that of the
      pristine graphitic carbon nitride counterpart). This work presents a facile
      method for designing and developing high-performance graphitic carbon nitride
      photocatalysts, providing a broad range of application prospects in the fields of
      electronics and energy conversion.

PMID- 29200262
TI  - On-Surface Growth Dynamics of Graphene Nanoribbons: The Role of Halogen
      Functionalization.
AB  - On-surface synthesis is a powerful route toward the fabrication of specific
      graphene-like nanostructures confined in two dimensions. This strategy has been
      successfully applied to the growth of graphene nanoribbons of diverse width and
      edge morphology. Here, we investigate the mechanisms driving the growth of 9-atom
      wide armchair graphene nanoribbons by using scanning tunneling microscopy, fast X
      ray photoelectron spectroscopy, and temperature-programmed desorption techniques.
      Particular attention is given to the role of halogen functionalization (Br or I)
      of the molecular precursors. We show that the use of iodine-containing monomers
      fosters the growth of longer graphene nanoribbons (average length of 45 nm) due
      to a larger separation of the polymerization and cyclodehydrogenation
      temperatures. Detailed insight into the growth process is obtained by analysis of
      kinetic curves extracted from the fast X-ray photoelectron spectroscopy data. Our
      study provides fundamental details of relevance to the production of future
      electronic devices and highlights the importance of not only the rational design
      of molecular precursors but also the most suitable reaction pathways to achieve
      the desired final structures.

PMID- 29200263
TI  - Phenylboronic Acid Templated Gold Nanoclusters for Mucin Detection Using a
      Smartphone-Based Device and Targeted Cancer Cell Theranostics.
AB  - A phenylboronic acid templated gold nanocluster probe was developed to detect
      biomarker mucin by a noninvasive fluorescence-based method using a point-of-care
      smartphone-based fluorescence detection device. The gold nanocluster probe is
      able to detect mucin specifically. The same probe was applied for in vitro
      targeted bioimaging of HeLa and Hep G2 cancer cells, and it demonstrated specific
      therapeutic effects toward cancer cells as well as multicellular tumor spheroids
      imparting theranostic properties. The module is found to be more effective toward
      HeLa cells, and a pathway of cell death was established using flow-cytometry
      based assays.

PMID- 29200264
TI  - Fully Coated Semitransparent Organic Solar Cells with a Doctor-Blade-Coated
      Composite Anode Buffer Layer of Phosphomolybdic Acid and PEDOT:PSS and a Spray
      Coated Silver Nanowire Top Electrode.
AB  - In the aim to realize high performance semitransparent fully coated organic solar
      cells, printable electrode buffer layers and top electrodes are two important key
      technologies. An ideal ink for the preparation of the electrode buffer layer for
      printed top electrodes should have good wettability and negligible solvent
      corrosion to the underlying layer. This work reports a novel organic-inorganic
      composite of phosphomolybdic acid (PMA) and PEDOT:PSS that features excellent
      wettability with the active layer and printed top Ag nanowires and high
      resistibility to solvent corrosion. This composite buffer layer can be easily
      deposited on a polymer surface to form a smooth, homogeneous film via spin
      coating or doctor-blade coating. Through the use of this composite anode buffer
      layer, fully coated semitransparent devices with doctor-blade-coated functional
      layers and spray-coated Ag nanowire top electrodes showed the highest power
      conversion efficiency (PCE) of 5.01% with an excellent average visible-light
      transmittance (AVT) of 50.3%, demonstrating superior overall characteristics with
      a comparable performance to and a much higher AVT than cells based on a thermally
      evaporated MoO3/Ag/MoO3 thin film electrode (with a PCE of 5.77% and AVT of
      19.5%). The current work reports the fabrication of fully coated inverted organic
      solar cells by combining doctor-blade coating and spray coating and, more
      importantly, demonstrates that a nanocomposite of a polyoxometalate and
      conjugated polymer could be an excellent anode buffer layer for the fully coated
      polymer solar cells with favorable interfacial contact, hole extraction
      efficiency, and high comparability with full printing.

PMID- 29200265
TI  - One-Step Preparation of Cesium Lead Halide CsPbX3 (X = Cl, Br, and I) Perovskite
      Nanocrystals by Microwave Irradiation.
AB  - CsPbX3 (X = Cl, Br, I) nanocrystals (NCs) are competitive emitting materials for
      illumination and display because of their outstanding photophysical properties.
      However, the conventional synthetic approaches suffer from low yields, complex
      procedures, and toxic chemicals. In this work, we demonstrate a one-step
      microwave-assisted approach to prepare CsPbX3 NCs. The homogeneous heating and
      rapid temperature increment of microwave preparation facilitate the growth of
      CsPbX3 NCs, producing the NCs with high photoluminescence quantum yields up to
      90%, narrow emission full-width at half-maximum, and emission color tunable from
      blue to red. By optimizing the preparation conditions of the microwave-assisted
      approach, CsPbX3 NCs with cation- and halide anion-controlled emission
      properties, tunable reaction rate, and enhanced stability are prepared. Light
      emitting diode (LED) prototypes are further fabricated by employing the as
      prepared CsPbX3 NCs as the color conversion materials on commercially available
      365 nm GaN LED chips.

PMID- 29200266
TI  - DNA Hybridization Assay Using Gold Nanoparticles and Electrophoresis Separation
      Provides 1 pM Sensitivity.
AB  - The efficiency of gold nanoparticle (AuNP) dimerization mediated by hybridization
      between two probe DNA molecules and a complementary target DNA molecule was
      maximized by examining several possible hybridization combinations. The
      uniformity of the size of the AuNPs, the use of surface modification appropriate
      for high hybridization efficiency, together with efficient blocking of
      nonspecific binding, all contributed to achieving a 1 pM detection limit
      following conventional gel electrophoresis separation of the DNA-modified AuNP
      multimers. This practical homogeneous DNA hybridization assay methodology will
      provide a rapid, cost-effective, and field-portable tool for clinical diagnosis.

PMID- 29200267
TI  - Mediated Electrochemical Reduction of Iron (Oxyhydr-)Oxides under Defined
      Thermodynamic Boundary Conditions.
AB  - Iron (oxyhydr-)oxide reduction has been extensively studied because of its
      importance in pollutant redox dynamics and biogeochemical processes. Yet,
      experimental studies linking oxide reduction kinetics to thermodynamics remain
      scarce. Here, we used mediated electrochemical reduction (MER) to directly
      quantify the extents and rates of ferrihydrite, goethite, and hematite reduction
      over a range of negative reaction free energies, DeltarG, that were obtained by
      systematically varying pH (5.0 to 8.0), applied reduction potentials (-0.53 to 
      0.17 V vs SHE), and Fe2+ concentrations (up to 40 MUM). Ferrihydrite reduction
      was complete and fast at all tested DeltarG values, consistent with its
      comparatively low thermodynamic stability. Reduction of the thermodynamically
      more stable goethite and hematite changed from complete and fast to incomplete
      and slow as DeltarG values became less negative. Reductions at intermediate
      DeltarG values showed negative linear correlations between the natural logarithm
      of the reduction rate constants and DeltarG. These correlations imply that
      thermodynamics controlled goethite and hematite reduction rates. Beyond allowing
      to study iron oxide reduction under defined thermodynamic conditions, MER can
      also be used to capture changes in iron oxide reducibility during phase
      transformations, as shown for Fe2+-facilitated transformation of ferrihydrite to
      goethite.

PMID- 29200269
TI  - Viologen-Based Photochromic Coordination Polymers for Inkless and Erasable
      Prints.
AB  - Four coordination polymers, namely, [Zn(HL1)(L2)0.5].H2O (1),
      [Cd(HL1)(L2)0.5].H2O (2), [Zn(L1)(L3)0.5].H2O (3), and [Cd(L1)(L3)0.5] (4) (H3L1
      = (3,5-dicarboxyl-phenyl)-(4-(2'-carboxyl-phenyl)-benzyl)ether, H2L2Cl2 = 1,1'
      bis(4-carboxy-benzyl)-4,4'-bipyridinium dichloride, and L3Cl2 = 1,1'-dimethyl
      4,4'-bipyridylium dichloride), have been synthesized hydrothermally. The
      structures of compounds 1-4 have been determined by single-crystal X-ray
      diffraction analyses, and further characterized by elemental analyses, infrared
      (IR) spectra, powder X-ray diffraction (PXRD) analyses, and thermogravimetric
      analyses. Compounds 1 and 2 display three-dimensional 2-fold interpenetrating
      frameworks, whereas compounds 3 and 4 exhibit two-dimensional layer structures.
      These compounds display photochromic behaviors from pale yellow to green under UV
      light, visible light, or sunlight. The photochromic mechanisms of these compounds
      have been studied by IR spectra, PXRD analyses, UV-vis absorption spectra,
      electron paramagnetic resonance spectra, density functional theory calculations,
      and X-ray photoelectron spectroscopy. The capabilities of compounds 1 and 2 as
      inkless and erasable printing media have also been tested. Moreover, the
      photomodulated fluorescence of these compounds has also been investigated.

PMID- 29200268
TI  - Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate
      Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation
      Reactions of Unactivated Secondary Halides.
AB  - Despite the long history of SN2 reactions between nitrogen nucleophiles and alkyl
      electrophiles, many such substitution reactions remain out of reach. In recent
      years, efforts to develop transition-metal catalysts to address this deficiency
      have begun to emerge. In this report, we address the challenge of coupling a
      carbamate nucleophile with an unactivated secondary alkyl electrophile to
      generate a substituted carbamate, a process that has not been achieved
      effectively in the absence of a catalyst; the product carbamates can serve as
      useful intermediates in organic synthesis as well as bioactive compounds in their
      own right. Through the design and synthesis of a new copper-based photoredox
      catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be
      activated upon irradiation by blue-LED lamps, we can achieve the coupling of a
      range of primary carbamates with unactivated secondary alkyl bromides at room
      temperature. Our mechanistic observations are consistent with the new copper
      complex serving its intended role as a photoredox catalyst, working in
      conjunction with a second copper complex that mediates C-N bond formation in an
      out-of-cage process.

PMID- 29200271
TI  - The Next Frontier: Quantitative Biochemistry in Living Cells.
AB  - Researchers striving to convert biology into an exact science foremost rely on
      structural biology and biochemical reconstitution approaches to obtain
      quantitative data. However, cell biological research is moving at an ever
      accelerating speed into areas where these approaches lose much of their edge.
      Intrinsically unstructured proteins and biochemical interaction networks composed
      of interchangeable, multivalent, and unspecific interactions pose unique
      challenges to quantitative biology, as do processes that occur in discrete
      cellular microenvironments. Here we argue that a conceptual change in our way of
      conducting biochemical experiments is required to take on these new challenges.
      We propose that reconstitution of cellular processes in vitro should be much more
      focused on mimicking the cellular environment in vivo, an approach that requires
      detailed knowledge of the material properties of cellular compartments,
      essentially requiring a material science of the cell. In a similar vein, we
      suggest that quantitative biochemical experiments in vitro should be accompanied
      by corresponding experiments in vivo, as many newly relevant cellular processes
      are highly context-dependent. In essence, this constitutes a call for chemical
      biologists to convert their discipline from a proof-of-principle science to an
      area that could rightfully be called quantitative biochemistry in living cells.
      In this essay, we discuss novel techniques and experimental strategies with
      regard to their potential to fulfill such ambitious aims.

PMID- 29200272
TI  - Stable Isotope-Resolved Analysis with Quantitative Dissolution Dynamic Nuclear
      Polarization.
AB  - Metabolite profiles and their isotopomer distributions can be studied
      noninvasively in complex mixtures with NMR. The advent of dissolution Dynamic
      Nuclear Polarization (dDNP) and isotope enrichment add sensitivity and resolution
      to such metabolic studies. Metabolic pathways and networks can be mapped and
      quantified if protocols that control and exploit the ex situ signal enhancement
      are created. We present a sample preparation method, including cell incubation,
      extraction and signal enhancement, to obtain reproducible and quantitative dDNP
      (qdDNP) NMR-based stable isotope-resolved analysis. We further illustrate how
      qdDNP was applied to gain metabolic insights into the phenotype of aggressive
      cancer cells.

PMID- 29200270
TI  - Arachidonic Acid Metabolism by Human Cardiovascular CYP2J2 Is Modulated by
      Doxorubicin.
AB  - Doxorubicin (DOX) is a chemotherapeutic that is used in the treatment of a wide
      variety of cancers. However, it causes cardiotoxicity partly because of the
      formation of reactive oxygen species. CYP2J2 is a human cytochrome P450 that is
      strongly expressed in cardiomyocytes. It converts arachidonic acid (AA) into four
      different regioisomers of epoxyeicosatrienoic acids (EETs). Using kinetic
      analyses, we show that AA metabolism by CYP2J2 is modulated by DOX. We show that
      cytochrome P450 reductase, the redox partner of CYP2J2, metabolizes DOX to 7
      deoxydoxorubicin aglycone (7-de-aDOX). This metabolite then binds to CYP2J2 and
      inhibits and alters the preferred site of metabolism of AA, leading to a change
      in the ratio of the EET regioisomers. Furthermore, molecular dynamics simulations
      indicate that 7-de-aDOX and AA can concurrently bind to the CYP2J2 active site to
      produce these changes in the site of AA metabolism. To determine if these
      observations are unique to DOX/7-de-aDOX, we use noncardiotoxic DOX analogues,
      zorubicin (ZRN) and 5-iminodaunorubicin (5-IDN). ZRN and 5-IDN inhibit CYP2J2
      mediated AA metabolism but do not change the ratio of EET regioisomers.
      Altogether, we demonstrate that DOX and 7-de-aDOX inhibit CYP2J2-mediated AA
      metabolism and 7-de-aDOX binds close to the active site to alter the ratio of
      cardioprotective EETs. These mechanistic studies of CYP2J2 can aid in the design
      of new alternative DOX derivatives.

PMID- 29200273
TI  - Nonpolar-to-Polar Phase Transition of a Chiral Ionic Plastic Crystal and Switch
      of the Rotation Symmetry.
AB  - The synthesis of a new ionic plastic crystal, tetraethylammonium-d20 d-10
      camphorsulfonate, is reported. The crystal has three solid phases, the structures
      of which were determined by single-crystal X-ray diffraction (XRD). XRD analysis
      revealed a phase transition from nonpolar space group P21212 to polar space group
      P21 with increasing temperature. The dynamics of the d-10-camphorsulfonate anion
      and the tetraethylammonium-d20 cation was investigated by variable-temperature 1H
      and 2H solid-state NMR spectroscopy. The anion showed swing motion in high
      temperature phases, which is in good agreement with the disorder observed in XRD
      analysis. The cation showed uniaxial rotation even in the low-temperature phase.
      The rotation axis of the tetrahedral structure showed a transition from the two
      fold axis to the three-fold axis with the phase transition.

PMID- 29200274
TI  - Shape Evolution of Biconcave Djurleite Cu1.94S Nanoplatelets Produced from CuInS2
      Nanoplatelets by Cation Exchange.
AB  - Development of nanomaterials of previously unavailable shapes and compositions
      continues to be a key need and interest in nanotechnology. Here, we report the
      preparation of unique biconcave djurleite Cu1.94S nanoplatelets (NPls) from
      template CuInS2 (copper indium sulfide, CIS) NPls via a cation exchange (CE)
      reaction. Upon initiation of the CE reaction, the In3+ ions diffuse out of the
      CIS crystal lattice, and the remaining copper sulfide adopts the djurleite phase
      almost instantly. This rapid phase transition produces numerous vacancies and
      defects before Cu+ ions can diffuse into the nanostructures. The formation of a
      biconcave shape is attributed to the assembly and migration of these defects. The
      flat surfaces of the NPls are ultimately restored through a ripening process that
      produces single-crystalline NPls much thicker than the starting templates.
      Striped NPls were observed in the final products, due to stacking faults at the
      boundary between newly deposited and residual layers of djurleite. These studies
      not only provide a better understanding of the relationships among composition,
      morphology, and crystal structure for copper sulfide-based nanocrystals, but also
      provide a pathway to a previously inaccessible morphology.

PMID- 29200275
TI  - Thiolation Protein-Based Transfer of Indolyl to a Ribosomally Synthesized
      Polythiazolyl Peptide Intermediate during the Biosynthesis of the Side-Ring
      System of Nosiheptide.
AB  - Nosiheptide, a potent bicyclic member of the family of thiopeptide antibiotics,
      possesses a distinctive l-Trp-derived indolyl moiety. The way in which this
      moiety is incorporated into a ribosomally synthesized and post-translationally
      modified thiopeptide remains poorly understood. Here, we report that NosK, an
      alpha/beta-hydrolase fold protein, mediates the transfer of indolyl from NosJ, a
      discrete thiolation protein, to a linear pentathiazolyl peptide intermediate
      rather than its genetically encoded untreated precursor. This intermediate
      results from enzymatic processing of the peptide precursor, in which five of the
      six l-Cys residues are transformed into thiazoles but Cys4 selectively remains
      unmodified for indolyl substitution via a thioester exchange. Determining the
      timing of indolyl incorporation, which expands the chemical space of a
      thiopeptide framework, facilitates mechanistic access to the unusual logic of
      post-translational modifications in the biosynthesis of nosiheptide-type
      thiopeptide members that share a similar compact side-ring system.

PMID- 29200276
TI  - Topologically Directed Assemblies of Semiconducting Sphere-Rod Conjugates.
AB  - Spontaneous organizations of designed elements with explicit shape and symmetry
      are essential for developing useful structures and materials. We report the
      topologically directed assemblies of four categories (a total of 24) of sphere
      rod conjugates, composed of a sphere-like fullerene (C60) derivative and a rod
      like oligofluorene(s) (OF), both of which are promising organic semiconductor
      materials. Although the packing of either spheres or rods has been well-studied,
      conjugates having both shapes substantially enrich resultant assembled
      structures. Mandated by their shapes and topologies, directed assemblies of these
      conjugates result not only in diverse unconventional semiconducting
      supramolecular lattices with controlled domain sizes but also in tunable charge
      transport properties of the resulting structures. These results demonstrate the
      importance of persistent molecular topology on hierarchically assembled
      structures and their final properties.

PMID- 29200277
TI  - Fast Startup of Semi-Pilot-Scale Anaerobic Digestion of Food Waste Acid
      Hydrolysate for Biogas Production.
AB  - In this study, a fast startup of semi-pilot-scale anaerobic digestion of food
      waste acid hydrolysate for biogas production was carried out for the first time.
      During the period of fast startup, more than 85% of chemical oxygen demand (COD)
      can be degraded, and even more than 90% of COD can be degraded during the later
      stage of anaerobic digestion. During this anaerobic digestion process, the biogas
      yield, the methane yield, and the CH4 content in biogas were 0.542 +/- 0.056
      m3/kgCOD consumption, 0.442 +/- 0.053 m3/kgCOD consumption, and 81.52 +/- 3.05%,
      respectively, and these values were high and stable. Besides, the fermentation pH
      was very stable, in which no acidification was observed during the anaerobic
      digestion process (outlet pH was 7.26 +/- 0.05 for the whole anaerobic
      digestion). Overall, the startup of this anaerobic digestion can be completed in
      a short period (the system can be stable 2 days after the substrate was pumped
      into the bioreactor), and anaerobic digestion of food waste acid hydrolysate is
      feasible and attractive for industrial treatment of food waste and biogas
      production.

PMID- 29200278
TI  - Sensomics-Based Molecularization of the Taste of Pot-au-Feu, a Traditional
      Meat/Vegetable Broth.
AB  - Targeted quantification of 49 basic taste-active molecules, followed by the
      calculation of dose-over-threshold (DoT) factors, and taste re-engineering
      experiments revealed minerals, nucleotides/nucleosides, amino acids, organic
      acids, and carbohydrates as the key compounds of Pot-au-Feu, a traditional broth
      preparation from beef cuts and vegetables. Moreover, the dipeptide carnosine was
      identified to be the key inducer for the white-meaty and thick-sour orosensation
      of the broth, next to anserine and 1-deoxy-d-fructosyl-N-beta-alanyl-l-histidine,
      the latter of which has been identified for the first time by means of a sensory
      guided fractionation. Sensory studies revealed the threshold concentration of
      carnosine in model broth to decrease by a factor of 5 upon nonenzymatic
      glycosylation to reach 4.4 mmol/L for its Amadori product 1-deoxy-d-fructosyl-N
      beta-alanyl-l-histidine.

PMID- 29200279
TI  - Ligand-Field Energy Splitting in Lanthanide-Based Single-Molecule Magnets by NMR
      Spectroscopy.
AB  - A method for the experimental determination of ligand-field (LF) energy splitting
      in mononuclear lanthanide complexes, based purely on variable-temperature NMR
      spectroscopy, was developed. The application of this method in an isostructural
      series of anionic lanthanide bis(cyclooctatetraenide) double-decker compounds
      bearing large rigid substituents is demonstrated. Using the three-nuclei plot
      approach devised by Reilley, the isostructurality of the compound series and the
      identical orientation of the magnetic main axis of all Ln3+ ions in the series
      Tb3+ to Tm3+ are demonstrated. Measurement of the 2H NMR spectra of partially
      deuterated analogues of the complexes permitted determination of the axial
      magnetic susceptibility anisotropies chiax for all five ions in the temperature
      range from 185 to 335 K. For this purpose, analysis of the hyperfine shifts was
      combined with structural models derived from density functional theory
      calculations. In a final step, the temperature dependence of the chiax values was
      used for determination of the three axial LF parameters, adapting a method
      employed previously for phthalocyanine-based systems. The temperature dependence
      dictated by the LF parameters determined by this NMR-based approach is compared
      to the results of recently published ab initio calculations of the system,
      indicating reasonable agreement of both methods. For all ions except Dy3+, the
      NMR method determines the same mJ ground state as the calculations and the order
      and energies of the excited states match well. However, the sign of the magnetic
      anisotropy of the dysprosium complex in the temperature range evaluated here is
      not correctly predicted by the published calculations but can be described
      accurately by the NMR approach. This shows that our experimental method for
      determination of the LF parameters is an ideal complementation to other
      theoretical and experimental methods.

PMID- 29200280
TI  - A Gigantic Molecular Wheel of {Gd140}: A New Member of the Molecular Wheel
      Family.
AB  - Nanoscale inorganic wheel-shaped structures are one of the most striking types of
      molecular aggregations. Here, we report the synthesis of a gigantic lanthanide
      wheel cluster containing 140 Gd3+ atoms. As the largest lanthanide cluster
      reported thus far, {Gd140} features an attractive wheel-like structure with 10
      fold symmetry. The nanoscopic molecular wheel possesses the largest diameter of
      6.0 nm and displays high stability in solution, which allows direct visualization
      by scanning transmission electron microscopy. The newly discovered lanthanide
      {Gd140} cluster represents a new member of the molecular wheel family.

PMID- 29200281
TI  - Discovery and Optimization of Thiazolidinyl and Pyrrolidinyl Derivatives as
      Inhaled PDE4 Inhibitors for Respiratory Diseases.
AB  - Phosphodiesterase 4 (PDE4) is a key cAMP-metabolizing enzyme involved in the
      pathogenesis of inflammatory disease, and its pharmacological inhibition has been
      shown to exert therapeutic efficacy in chronic obstructive pulmonary disease
      (COPD). Herein, we describe a drug discovery program aiming at the identification
      of novel classes of potent PDE4 inhibitors suitable for pulmonary administration.
      Starting from a previous series of benzoic acid esters, we explored the chemical
      space in the solvent-exposed region of the enzyme catalytic binding pocket.
      Extensive structural modifications led to the discovery of a number of
      heterocycloalkyl esters as potent in vitro PDE4 inhibitors. (S*,S**)-18e and
      (S*,S**)-22e, in particular, exhibited optimal in vitro ADME and pharmacokinetics
      properties and dose-dependently counteracted acute lung eosinophilia in an
      experimental animal model. The optimal biological profile as well as the
      excellent solid-state properties suggest that both compounds have the potential
      to be effective topical agents for treating respiratory inflammatory diseases.

PMID- 29200282
TI  - Incomplete Refolding of Antibody Light Chains to Non-Native, Protease-Sensitive
      Conformations Leads to Aggregation: A Mechanism of Amyloidogenesis in Patients?
AB  - Genetic, biochemical, and pharmacologic evidence supports the hypothesis that
      conformationally altered or misfolded protein states enable aggregation and
      cytotoxicity in the systemic amyloid diseases. Reversible structural fluctuations
      of natively folded proteins are involved in the aggregation of many degenerative
      disease associated proteins. Herein, we use antibody light chains (LCs) that form
      amyloid fibrils in AL amyloidosis to consider an alternative hypothesis of
      amyloidogenesis: that transient unfolding and incomplete extracellular refolding
      of secreted proteins can lead to metastable, alternatively folded states that are
      more susceptible to aggregation or to endoproteolysis that can release
      aggregation-prone fragments. Refolding of full-length lambda6a LC dimers
      comprising an interchain disulfide bond from heat- or chaotrope-denatured
      ensembles in buffers yields the native dimeric state as well as alternatively
      folded dimers and aggregates. LC variants lacking an interchain disulfide bond
      appear to refold fully reversibly to the native state. The conformation of a
      backbone peptidyl-proline amide in the LC constant domain, which is cis in the
      native state, may determine whether the LC refolds back to the native state. A
      proline to alanine (P147A) LC variant, which cannot form the native cis-amide
      conformation, forms amyloid fibrils from the alternatively folded ensemble,
      whereas all the full-length lambda6a LCs we have studied to date do not form
      amyloid under analogous conditions. P147A LC variants are susceptible to
      endoproteolysis by thrombin, enabling amyloidogenesis of the fragments released.
      Thus, non-native LC structural ensembles containing a tyrosine 146-proline 147
      trans-amide bond can initiate and propagate amyloid formation, either directly or
      after aberrant endoproteolysis.

PMID- 29200283
TI  - In Vitro Biosynthetic Studies of Bottromycin Expand the Enzymatic Capabilities of
      the YcaO Superfamily.
AB  - The bottromycins belong to the ribosomally synthesized and posttranslationally
      modified peptide (RiPP) family of natural products. Bottromycins exhibit unique
      structural features, including a hallmark macrolactamidine ring and thiazole
      heterocycle for which divergent members of the YcaO superfamily have been
      biosynthetically implicated. Here we report the in vitro reconstitution of two
      YcaO proteins, BmbD and BmbE, responsible for the ATP-dependent cyclodehydration
      reactions that yield thiazoline- and macrolactamidine-functionalized products,
      respectively. We also establish the substrate tolerance for BmbD and BmbE and
      systematically dissect the role of the follower peptide, which we show serves a
      purpose similar to canonical leader peptides in directing the biosynthetic
      enzymes to the substrate. Lastly, we leverage the expanded capabilities of YcaO
      proteins to conduct an extensive bioinformatic survey to classify known YcaO
      chemistry. This analysis predicts new functions remain to be uncovered within the
      superfamily.

PMID- 29200284
TI  - Bismuth-Induced Inactivation of Ferric Uptake Regulator from Helicobacter pylori.
AB  - Ferric uptake regulator (Fur) of Helicobacter pylori is a global regulator that
      is important for bacterial colonization and survival within the gastric mucosa.
      H. pylori Fur (HpFur) is unique in its ability to regulate gene expression in
      both metal-bound (holo-Fur) and metal-free (apo-Fur) forms. Bismuth-based drugs
      are widely used for the treatment of H. pylori infection. However, the mechanism
      of action of bismuth drug was not fully understood. Recently, it has been
      reported that bismuth drugs could interfere with the bacterial ferric uptake
      pathway and inhibit bacterial growth, implying intrinsic correlation between
      bismuth drug and bacterial iron metabolism. Herein, we demonstrate that Bi(III)
      binds to HpFur protein specifically at the physiologically important S1 site,
      which further leads to protein oligomerization and loss of DNA binding
      capability. The targeting of HpFur by bismuth drugs significantly reduced
      transcription levels of its regulated genes, which are crucial for bacterial
      physiology and metabolism. Our studies present direct evidence that perturbation
      of iron metabolism in H. pylori by bismuth might serve as one of the mechanisms
      for the antimicrobial activity of bismuth drugs.

PMID- 29200285
TI  - Site-Specific Modification of Single-Chain Antibody Fragments for Bioconjugation
      and Vascular Immunotargeting.
AB  - The conjugation of antibodies to drugs and drug carriers improves delivery to
      target tissues. Widespread implementation and effective translation of this
      pharmacologic strategy awaits the development of affinity ligands capable of a
      defined degree of modification and highly efficient bioconjugation without loss
      of affinity. To date, such ligands are lacking for the targeting of therapeutics
      to vascular endothelial cells. To enable site-specific, click-chemistry
      conjugation to therapeutic cargo, we used the bacterial transpeptidase, sortase
      A, to attach short azidolysine containing peptides to three endothelial-specific
      single chain antibody fragments (scFv). While direct fusion of a recognition
      motif (sortag) to the scFv C-terminus generally resulted in low levels of sortase
      mediated modification, improved reaction efficiency was observed for one protein,
      in which two amino acids had been introduced during cloning. This prompted
      insertion of a short, semi-rigid linker between scFv and sortag. The linker
      significantly enhanced modification of all three proteins, to the extent that
      unmodified scFv could no longer be detected. As proof of principle, purified,
      azide-modified scFv was conjugated to the antioxidant enzyme, catalase, resulting
      in robust endothelial targeting of functional cargo in vitro and in vivo.

PMID- 29200286
TI  - Ligand Effect on the Single-Molecule Magnetism of Tetranuclear Co(II) Cubane.
AB  - A clear dependence on the ligand has been observed for the magnetic properties of
      a closely related series of Co(II) cubane structures, viz. [Co4(mbm or
      bm)4(ROH)4Br4] (1-MeOH, 1-EtOH, 2-MeOH, and 2-EtOH, where 1 = [Co4(mbm)4Br4], 2 =
      [Co4(bm)4Br4], bm = (1H-benzo[d]imidazol-2-yl)methanolate. and mbm = 1-Me-bm.)
      The [Co4(OR)4] cubane core consists of an octahedral CoII center chelated by the
      alkoxide oxygen and imidazole nitrogen atoms from monoanionic bm or mbm and
      coordinated by methanol/alcohol and bromine. Interestingly, electrospray
      ionization mass spectrometry (ESI-MS) indicates that 1-MeOH and 2-MeOH are
      unstable in methanol and transformed to the butterfly [Co4L6]2+ but that 1-EtOH
      and 2-EtOH are stable in ethanol. Their magnetic susceptibilities suggest
      ferromagnetic coupling between the nearest cobalt centers to give a theoretical S
      = 4 * 3/2 ground state with considerable magneto-crystalline behavior. The
      packing and intermolecular interactions appear to influence the geometry of the
      cubes and thus the anisotropy of cobalt, which leads to different blocking
      temperatures (TB). Consequently, the compounds with mbm, 1-MeOH and 1-EtOH,
      exhibit TB > 2 K as shown by the relaxation of magnetization in zero applied dc
      field where the barriers Ueff/kB are respectively 27 and 21 K and relaxation
      times are tau0 = 1.3 * 10-9 and 9.7 * 10-9 s. However, the compounds with bm, 2
      MeOH and 2-EtOH, remain paramagnetic above 2 K and do not show nonlinear response
      of the ac susceptibilities. These findings reaffirm the subtle dependence of
      single-molecule magnetism on coordination geometry and intermolecular
      interaction.

PMID- 29200288
TI  - Novel Molecules To Treat Chronic Central Nervous System Toxoplasmosis.
AB  - A major challenge in treating toxoplasmosis in immunocompromised patients is lack
      of therapeutic agents to clear chronic infection and stop the recrudescence of
      infection after therapy. CDKP1 has emerged as a novel target for treating chronic
      infections and eliminating latent bradyzoites in the brain. In a mouse model of
      toxoplasmosis, pyrazolopyrimidine inhibitors of Toxoplasma gondii CDPK1
      demonstrated in vitro and in vivo efficacy.

PMID- 29200289
TI  - Ab Initio Simulations of Water Dynamics in Aqueous TMAO Solutions: Temperature
      and Concentration Effects.
AB  - We use ab initio molecular dynamics simulation to study the effect of hydrophobic
      groups on the dynamics of water molecules in aqueous solutions of trimethylamine
      N-oxide (TMAO). We show that hydrophobic groups induce a moderate (<2-fold)
      slowdown of water reorientation and hydrogen-bond dynamics in dilute solutions,
      but that this slowdown rapidly increases with solute concentration. In addition,
      the slowdown factor is found to vary very little with temperature, thus
      suggesting an entropic origin. All of these results are in quantitative agreement
      with prior classical molecular dynamics simulations and with the previously
      suggested excluded-volume model. The hydrophilic TMAO headgroup is found to
      affect water dynamics more strongly than the hydrophobic moiety, and the
      magnitude of this slowdown is very sensitive to the strength of the water-solute
      hydrogen-bond.

PMID- 29200290
TI  - First-Principles Molecular Dynamics Study of a Deep Eutectic Solvent: Choline
      Chloride/Urea and Its Mixture with Water.
AB  - First-principles molecular dynamics simulations in the canonical ensemble at
      temperatures of 333 and 363 K and at the corresponding experimental densities are
      carried out to investigate the behavior of the 1:2 choline chloride/urea (reline)
      deep eutectic solvent and its equimolar mixture with water. Analysis of atom-atom
      radial and spatial distribution functions and of the H-bond network reveals the
      microheterogeneous structure of these complex liquid mixtures. In neat reline,
      the structure is governed by strong H-bonds of the trans- and cis-H atoms of urea
      to the chloride ion. In hydrous reline, water competes for the anions, and the H
      atoms of urea have similar propensities to bond to the chloride ions and the O
      atoms of urea and water. The vibrational spectra exhibit relatively broad peaks
      reflecting the heterogeneity of the environment. Although the 100 ps trajectories
      allow only for a qualitative assessment of transport properties, the simulations
      indicate that water is more mobile than the other species and its addition also
      fosters faster motion of urea.

PMID- 29200291
TI  - Correction to Mutational Replacements at the "Glycine Hinge" of the Escherichia
      coli Chemoreceptor Tsr Support a Signaling Role for the C-Helix Residue.

PMID- 29200287
TI  - Drug-Drug Interactions between Atorvastatin and Dronedarone Mediated by Monomeric
      CYP3A4.
AB  - Heterotropic interactions between atorvastatin (ARVS) and dronedarone (DND) have
      been deciphered using global analysis of the results of binding and turnover
      experiments for pure drugs and their mixtures. The in vivo presence of
      atorvastatin lactone (ARVL) was explicitly taken into account by using pure ARVL
      in analogous experiments. Both ARVL and ARVS inhibit DND binding and metabolism,
      while a significantly higher affinity of CYP3A4 for ARVL makes the latter the
      main modulator of activity (effector) in this system. Molecular dynamics
      simulations reveal significantly different modes of interactions of DND and ARVL
      with the substrate binding pocket and with a peripheral allosteric site.
      Interactions of both substrates with residues F213 and F219 at the allosteric
      site play a critical role in the communication of conformational changes induced
      by effector binding to productive binding of the substrate at the catalytic site.

PMID- 29200292
TI  - Metastable State during Melting and Solid-Solid Phase Transition of [CnMim][NO3]
      (n = 4-12) Ionic Liquids by Molecular Dynamics Simulation.
AB  - We simulate the heating process of ionic liquids [CnMim][NO3] (n = 4, 6, 8, 10,
      12), abbreviated as Cn, by means of molecular dynamics (MD) simulation starting
      from a manually constructed triclinic crystal structure composed of polar layers
      containing anions and cationic head groups and nonpolar regions in between
      containing cationic alkyl side chains. During the heating process starting from
      200 K, each system undergoes first a solid-solid phase transition at a lower
      temperature, and then a melting phase transition at a higher temperature to an
      isotropic liquid state (C4, C6, and C8) or to a liquid crystal state (C10 and
      C12). After the solid-solid phase transition, all systems keep the triclinic
      space symmetry, but have a different set of lattice constants. C4 has a more
      significant structural change in the nonpolar regions which narrows the layer
      spacing, while the layer spacings of other systems change little, which can be
      qualitatively understood by considering that the contribution of the effective
      van der Waals interaction in the nonpolar regions (abbreviated as EF1) to free
      energy becomes stronger with increasing side-chain length, and at the same time
      the contribution of the effective electrostatic interaction in the polar layers
      (abbreviated as EF2) to free energy remains almost the same. The melting phase
      transitions of all systems except C6 are found to be a two-step process with an
      intermediate metastable state appeared during the melting from the crystal state
      to the liquid or liquid crystal state. Because the contribution of EF2 to the
      free energy is larger than EF1, the metastable state of C4 has the feature of
      having higher ordered polar layers and lower ordered side-chain orientation. By
      contrast, C8-C12 have the feature of having lower ordered polar layers and higher
      ordered side-chain orientation, because for these systems, the contribution of
      EF2 to the free energy is smaller than EF1. No metastable state is found for C6
      because the free-energy contribution of EF1 is balanced with EF2.

PMID- 29200293
TI  - Dual-Functional Tamm-Dancoff Approximation with Self-Interaction-Free Orbitals:
      Vertical Excitation Energies and Potential Energy Surfaces near an Intersection
      Seam.
AB  - Recently we have developed the dual-functional Tamm-Dancoff approximation (DF
      TDA) method. DF-TDA is an alternative to linear-response time-dependent density
      functional theory (LR-TDDFT) with the advantage of providing a correct double
      cone topology of S1/S0 conical intersections. In the DF-TDA method, we employ
      different functionals, which are denoted G and F, for orbital optimization and
      Hamiltonian construction. We use the notation DF-TDA/G:F. In the current work, we
      propose that G be the same as F except for having 100% Hartree-Fock exchange. We
      use the notation F100 to denote functional F with this modification. A motivation
      for this is that functionals with 100% Hartree-Fock exchange are one-electron
      self-interaction-free. Here we validate the use of F100/M06 to compute vertical
      excitation energies and the global potential energy surface of ammonia near a
      conical intersection to further validate the F100 method for photochemical
      problems.

PMID- 29200294
TI  - Eudesmane Sesquiterpenes from Verbesina lanata with Inhibitory Activity against
      Grapevine Downy Mildew.
AB  - An in-house library of more than 3000 extracts of plant and fungal origin was
      screened against some major plant pathogens. As one of the hits, an ethyl acetate
      extract from inflorescences of Verbesina lanata showed significant inhibitory
      activity in vitro against grapevine downy mildew (Plasmopara viticola), with a
      MIC100 value of 35 MUg/mL. An emulsifiable concentrate formulation with 50 mg/g
      of the extract was developed for in vivo evaluation. A suspension of the
      formulation containing 1 mg/mL of extract lowered leaf surface infection of
      grapevine seedling by 82% compared to the nontreated control. With the aid of
      HPLC-based activity profiling, the antifungal activity was correlated with a
      series of lipophilic compounds. Preparative isolation by a combination of
      chromatographic techniques afforded 16 eudesmane sesquiterpenes including eight
      new congeners. Nine compounds were obtained in sufficient quantities to be tested
      in vitro and were found to inhibit the zoospore activity of P. viticola with
      MIC100 values ranging from 4 to 50 MUg/mL. The two major compounds, 6beta
      cinnamoyloxy-4beta,9beta,15-trihydroxyeudesmane (9) and 6beta-cinnamoyloxy
      1beta,15-dihydroxyeudesm-4-en-3-one (13), showed MIC100 values of 5 and 31
      MUg/mL, respectively.

PMID- 29200296
TI  - Computational Comparison of Different Reagent Ions in the Chemical Ionization of
      Oxidized Multifunctional Compounds.
AB  - High pressure anion chemical ionization is commonly used for the detection of
      neutral molecules in the gas phase. The detection efficiency in these
      measurements depends on how strongly the reagent ion binds to the neutral target
      molecule. We have calculated the binding strength of nitrate (NO3-), acetate
      (CH3C(O)O-), lactate (CH3CH(OH)C(O)O-), trifluoroacetate (CF3C(O)O-),
      trifluoromethanolate (CF3O-), bromide (Br-), and iodide (I-) reagent ions to ten
      different products derived from the OH radical-initiated oxidation of butadiene.
      We found that the binding of these oxidation products to the reagent ions depends
      almost linearly on the number of oxygen atoms in the target molecule, with the
      precise chemical identity of the compound (e.g., the number and relative position
      of hydroxyl or hydroperoxy groups) playing a more minor role. For acetate, the
      formation free energy decreases on average by around 4 kcal/mol when the number
      of oxygen atoms in the sample molecule increases by one. For the other reagent
      ions the corresponding decrease is around 3 kcal/mol. For all of the molecules
      studied, acetate forms the most stable clusters and I- the least stable. We also
      investigated the effect of humidity on the chemical ionization by calculating how
      strongly water molecules bind to both the reagent ions and the ion-molecule
      clusters. Water binds much more strongly to the reagent ion monomers compared to
      the reagent ion "dimers" (defined here as a cluster of the reagent anion with the
      corresponding neutral conjugate acid, e.g., HNO3(NO3-)) or the ion-molecule
      clusters. This likely leads to a stronger humidity dependence when using reagent
      ions that are not able to form reagent ion dimers (such as CF3C(O)O-, CF3O-, Br-,
      and I-).

PMID- 29200295
TI  - Fluorous l-Carbidopa Precursors: Highly Enantioselective Synthesis and
      Computational Prediction of Bioactivity.
AB  - New fluorous enantiopure (S)-alpha-aminated beta-keto esters were prepared
      through a highly enantioselective electrophilic alpha-amination step in the
      presence of europium triflate and (R,R)-phenyl-pybox. These compounds are
      precursors of fluorinated analogues of l-carbidopa, which is known to inhibit
      DOPA decarboxylase (DDC), a key protein in Parkinson's disease. Fluorination
      provides better stability for biological applications, which could possibly lead
      to DDC inhibitors better than l-carbidopa itself. Induced fit docking
      computational simulations performed on the new structures interacting with DDC
      highlight that for an efficient binding at the DDC site, at least one hydroxyl
      substituent must be present at the aromatic ring of the l-carbidopa analogues and
      show that the presence of fluorine can further fix the position of the ligand in
      the active site.

PMID- 29200297
TI  - Pitch and Handedness of the Cholesteric Order in Films of a Chiral Alternating
      Fluorene Copolymer.
AB  - The molecular organization in thermally annealed films of poly(9,9-bis((S)-3,7
      dimethyloctyl)-2,7-fluorene-alt-benzothiadiazole) is investigated using polarized
      light. Measurement of linear polarization in transmission and reflection as a
      function of layer thickness and orientation directly show a left handed
      cholesteric organization with a pitch length of 600 nm. Results are corroborated
      by measurements of circularly polarized reflection and generalized ellipsometry
      and are compared to calculations of the optical properties based on the Maugin
      Oseen-DeVries model. For wavelengths near the lowest allowed optical transition,
      light with the same handedness as the cholesteric arrangement (left) is found to
      be reflected and transmitted with a probability higher than right circularly
      polarized light. The high transmission for left polarized light is interpreted as
      an optical manifestation of the Borrmann effect.

PMID- 29200298
TI  - Molecular Dynamics Study of the Collision-Induced Reaction of H with CO on Small
      Water Clusters.
AB  - The successive hydrogenation of CO is supposed to be the main mechanism leading
      to the formation of complex oxygenated species in the interstellar medium,
      possibly mediated by ice layers or ice grains. In order to simulate the dynamical
      influence of a water environment on the first step of the hydrogenation process,
      we perform molecular dynamics simulations of the reactive collision of H with CO
      adsorbed on water clusters in the framework of the self-consistent-charge density
      functional based tight-binding approach (SCC-DFTB) to calculate potential energy
      surfaces. The reaction probabilities and the reactive cross sections are
      determined for water cluster sizes up to ten water molecules. The collision
      results are analyzed in terms of different reaction pathways: reactive or
      nonreactive, sticking or desorption of the products or reactants. We show that
      the HCO radical, although potentially formed as an intermediate regardless of the
      size of the water cluster, is significantly stabilized for cluster sizes larger
      than one water molecule and may remain adsorbed on water clusters with more than
      three molecules. This behavior is shown to be linked with the dissipation of the
      collision energy into vibrational excitation of the water cluster.

PMID- 29200299
TI  - Solvation Structure of Sodium Bis(fluorosulfonyl)imide-Glyme Solvate Ionic
      Liquids and Its Influence on Cycling of Na-MNC Cathodes.
AB  - Electrolytes consisting of sodium bis(fluorosulfonyl)imide (NaFSI) dissolved in
      glymes (monoglyme, diglyme, and triglyme) were characterized by FT-Raman
      spectroscopy and 13C, 17O, and 23Na NMR spectroscopy. The glyme:NaFSI molar ratio
      was varied from 50:1 to 1:1, and it was observed that, in the dilute
      electrolytes, the sodium salt is completely dissociated into solvent separated
      ion pairs (SSIPs). However, contact ion pairs (CIPs) and aggregates (AGGs) become
      the predominant species in more concentrated solutions. Some of the electrolytes
      with the highest concentrations can be classified as solvate ionic liquids
      (SILs), where all of the solvent molecules are coordinated to sodium cations.
      Therefore, these electrolytes are fundamentally different from more dilute
      electrolytes which are typically used in commercially available secondary
      batteries. The melting point or glass transition temperature, dynamic viscosity,
      density, sodium concentration, and ionic conductivity of these solvate ionic
      liquids are reported as well as the crystal structures of [Na(G3)][FSI] and
      [Na(G3)2][FSI]. Galvanostatic cycling experiments were performed in coin-type
      cells with a Na2/3[Mn0.55Ni0.30Co0.15]O2 cathode to study the influence of these
      electrolytes on the electrochemical stability and charge/discharge behavior.

PMID- 29200300
TI  - Experimental and Molecular Modeling Evaluation of the Physicochemical Properties
      of Proline-Based Deep Eutectic Solvents.
AB  - The liquid range and applicability of deep eutectic solvents (DESs) are
      determined by their physicochemical properties. In this work, the physicochemical
      properties of glycolic acid:proline and malic acid:proline were evaluated
      experimentally and with MD simulations at five different ratios. Both DESs
      exhibited esterification upon preparation, which affected the viscosity in
      particular. In order to minimize oligomer formation and water release, three
      different experimental preparation methods were explored, but none could prevent
      esterification. The experimental and calculated densities of the DESs were found
      to be in good agreement. The measured and modeled glass transition temperature
      showed similar trends with composition, as did the experimental viscosity and the
      calculated diffusivities. The MD simulations provided additional insight at the
      atomistic level, showing that at acid-rich compositions, the acid-acid hydrogen
      bonding (HB) interactions prevail. Malic acid-based DESs show stronger acid-acid
      HB interactions than glycolic acid-based ones, possibly explaining its extreme
      viscosity. Upon the addition of proline, the interspecies interactions become
      predominant, confirming the formation of the widely assumed HB network between
      the DESs constituents in the liquid phase.

PMID- 29200301
TI  - Selectivity of Glycine for Facets on Gold Nanoparticles.
AB  - The performance of nanoparticles in medical applications depends on their
      interactions with various molecules. Despite extensive research on this subject,
      it remains unclear where on an inhomogeneous nanoparticle molecules prefer to
      adsorb. Here we investigate the selectivity of glycine molecules for facets on
      five bare gold nanoparticles with diameters from 1.0 to 5.0 nm. Well-tempered
      metadynamics simulations are conducted to calculate the adsorption free-energy
      landscapes of a glycine molecule on various locations for the five gold
      nanoparticles in explicit water. We also calculate the glycine molecule's
      adsorption free energies on the five gold nanoparticles in vacuum and on three
      flat gold surfaces as a reference. The simulation results show that glycine
      molecules prefer to adsorb on the (110) facet for the 1.0 and 2.0 nm
      nanoparticles, the edges for the 3.0 nm nanoparticle, and the (111) facet for the
      4.0 and 5.0 nm nanoparticles in water. The effect of water solvent on the
      selectivity is investigated through comparing the adsorption free-energy
      landscapes for glycine molecules on the nanoparticles in water and in vacuum. The
      area of the facet plays a key role in determining the selectivity of glycine
      molecules for the different facets, especially the shift of the selectivity as
      the nanoparticle diameter changes. Our simulations suggest that nanoparticle size
      and shape can be engineered to control the preferred adsorption location of
      molecules.

PMID- 29200302
TI  - Activated Wetting of Nanostructured Surfaces: Reaction Coordinates, Finite Size
      Effects, and Simulation Pitfalls.
AB  - A liquid in contact with a textured surface can be found in two states, Wenzel
      and Cassie. In the Wenzel state the liquid completely wets the corrugations while
      in the Cassie state the liquid is suspended over the corrugations with air or
      vapor trapped below. The superhydrophobic properties of the Cassie state are
      exploited for self-cleaning, drag reduction, drug delivery, etc., while in the
      Wenzel state most of these properties are lost; it is therefore of great
      fundamental and technological interest to investigate the kinetics and mechanism
      of the Cassie-Wenzel transition. Computationally, the Cassie-Wenzel transition is
      often investigated using enhanced sampling ("rare events") techniques based on
      the use of collective variables (CVs). The choice of the CVs is a crucial task
      because it affects the free-energy profile, the estimation of the free-energy
      barriers, and the evaluation of the mechanism of the process. Here we investigate
      possible simulation artifacts introduced by common CVs adopted for the study of
      the Cassie-Wenzel transition: the average particle density in the corrugation of
      a textured surface and the coarse-grained density field at various levels of
      coarse graining. We also investigate possible additional artifacts associated
      with finite size effects. We focus on a pillared surface, a system often used in
      technological applications. We show that the use of a highly coarse-grained
      density (a single CV) of the fluid in the interpillar region brings to severe
      artifacts: errors of hundreds of kBT in the difference of free energy between the
      Cassie and Wenzel states, of tens of kBT in the estimate of the free-energy
      barriers, and erroneous wetting mechanisms. A proper description of the wetting
      mechanism and its energetics apparently requires a fine discretization of the
      density field. Concerning the finite-size effects, we have found that the typical
      systems employed in simulations of the Cassie-Wenzel transition, containing a
      single pillar within periodic boundary conditions, prevent the complete break of
      translational symmetry of the liquid-vapor meniscus during the process. Capturing
      this break of symmetry is crucial for describing the transition state along the
      wetting process and the early stage of the opposite process, the Wenzel-Cassie
      transition.

PMID- 29200303
TI  - Effect of Glucose on the Mobility of Membrane-Adhering Liposomes.
AB  - Enclosed lipid bilayer structures, referred to as liposomes or lipid vesicles,
      have a wide range of biological functions, such as cellular signaling and
      membrane trafficking. The efficiency of cellular uptake of liposomes, a key step
      in many of these functions, is strongly dependent on the contact area between a
      liposome and a cell membrane, which is governed by the adhesion force w, the
      membrane bending energy kappa, and the osmotic pressure Deltap. Herein, we
      investigate the relationship between these forces and the physicochemical
      properties of the solvent, namely, the presence of glucose (a nonionic osmolyte).
      Using fluorescence microscopy, we measure the diffusivity D of small (~50 nm
      radius), fluorescently labeled liposomes adhering to a supported lipid bilayer or
      to the freestanding membrane of a giant (~10 MUm radius) liposome. It is observed
      that glucose in solution reduces D on the supported membrane, while having
      negligible effect on D on the freestanding membrane. Using well-known
      hydrodynamic theory for the diffusivity of membrane inclusions, these
      observations suggest that glucose enhances the contact area between the small
      liposomes and the underlying membrane, while not affecting the viscosity of the
      underlying membrane. In addition, quartz crystal microbalance experiments showed
      no significant change in the hydrodynamic height of the adsorbed liposomes, upon
      adding glucose. This observation suggests that instead of osmotic deflation,
      glucose enhances the contact area via adhesion forces, presumably due to the
      depletion of the glucose molecules from the intermembrane hydration layer.

PMID- 29200304
TI  - Salt-Responsive Fe3O4 Nanocomposites and Phase Behavior in Water.
AB  - The ability to achieve exquisite control over polymer building blocks within
      multicompartment magnetite nanocomposites (NCs) to afford predictable and ordered
      packing hierarchical structures remains a significant challenge for the design of
      NCs. Thus, there is an urgent need to develop new types of nano-dimensional
      assemblies that undergo responsive shape shift, size, phase, and morphological
      transitions, especially for processes that are triggered by biologically relevant
      stimuli such as ionic gradients to meet the demand for diverse applications.
      Accordingly, we report an unprecedented concept for the preparation of salt
      responsive magnetite/polyaniline composite nanoassemblies with chemically
      distinct dual-compartment structures. The size, shape, and nano-dimensional phase
      separation of the PANI assemblies within NCs were adjusted in a facile manner
      with incremental changes in salt gradients using NaCl(aq). Composition effects
      bestow desirable diversiform shape, size, and phase behavior of the incorporated
      conductive polymer via dynamic H-bonding. The size, shape, and superparamagnetic
      character of iron oxide nanoparticles (IONPs) are unaffected by a "salting-in"
      process. The mechanism, gradual morphological evolution, interchangeable
      nanophase separation, and ion-stimulated disassembly of PANI building blocks for
      these magneto/ion-responsive polymer-composites at elevated ionic strength are
      strongly supported by DLS, Raman spectroscopy, TEM, and equilibrium dye (MB/MO)
      recognition studies.

PMID- 29200305
TI  - Total Synthesis of Propolisbenzofuran B.
AB  - An efficient synthesis of propolisbenzofuran B, which possesses promising
      anticancer activity, is reported. The key cyclohexanone framework of this
      tricyclic natural product has been constructed employing a Rh-catalyzed
      intramolecular olefin hydroacylation. The requisite key olefin intermediate was
      synthesized by using gold-catalyzed allenyl ether [1,3] O -> C rearrangement.

PMID- 29200306
TI  - Self-Assembled Ligands Targeting TLR7: A Molecular Level Investigation.
AB  - Toll-like receptors (TLRs) are pattern recognition transmembrane proteins that
      play an important role in innate immunity. In particular, TLR7 plays a role in
      detecting nucleic acids derived from viruses and bacteria. The huge number of
      pathologies in which TLR7 is involved has led to an increasing interest in
      developing new compounds targeting this protein. Several conjugation strategies
      were proposed for TLR7 agonists to increase the potency while maintaining a low
      toxicity. In this work, we focus the attention on two promising classes of TLR7
      compounds derived from the same pharmacophore conjugated with phospholipid and
      polyethylene glycol (PEG). A multidisciplinary investigation has been carried out
      by molecular dynamics (MD), dynamic light scattering (DLS), electron paramagnetic
      resonance (EPR), and cytotoxicity assessment. DLS and MD indicated how only the
      phospholipid conjugation provides the compound abilities to self-assemble in an
      orderly fashion with a maximal pharmacophore exposition to the solvent. Further
      EPR and cytotoxicity experiments highlighted that phospholipid compounds organize
      in stable aggregates and well interact with TLR7, whereas PEG conjugation was
      characterized by poorly stable aggregates at the cells surface. The
      methodological framework proposed in this study may be used to investigate, at a
      molecular level, the interactions generally occurring between aggregated ligands,
      to be used as drugs, and protein receptors.

PMID- 29200307
TI  - Binding of 12-Crown-4 with Alzheimer's Abeta40 and Abeta42 Monomers and Its
      Effect on Their Conformation: Insight from Molecular Dynamics Simulations.
AB  - Alzheimer's disease is the most common form of dementia and is considered to be
      caused by the conformational change of Abeta monomers, from their native
      monomeric states, to form Abeta oligomers/aggregates in the brain. Turn formation
      in Abeta monomer has been suggested to be the nucleation step for Abeta
      misfolding. In the present work, we have performed a series of all-atom molecular
      dynamics simulations, a total time of 11.4 MUs, to elucidate factor that
      contributes for early stage misfolding of Abeta40 and Abeta42 monomers and
      reveals the binding modes of 12-crown-4 on Abeta40 and Abeta42 monomer and effect
      of its binding on structural stability. Our simulation data revealed that the
      region around Val24-Lys28 is most prevalent for turn formation and a gain of
      water molecules around Lys28 side chains occurs at the same time as a significant
      gain in conformational entropy of the side chain. The initiation steps lead a
      greater number of water molecules available and enhancement of the conformational
      entropy of the backbone atoms; this leads to greater probability of breaking
      Lys28 backbone intrapeptide H-bonds, and consequently turns formation.
      Simulations of Abeta40 and Abeta42 monomers with 12-crown-4 showed that the
      molecule is highly specific toward positively charged Lys16, Lys28 residues, and
      N-terminal Asp1. Lys16 and Asp1 have been previously reported to make Abeta
      peptide toxic. Our secondary structure analysis revealed that in the absence of
      12-crown-4 there was a beta-sheet formed in the Abeta40 peptide. In case of
      Abeta42 monomer, in the absence of 12-crown-4, we observed that the second helix
      region converted into a coil and turn; however, in the presence of 12-crown-4 it
      remained stable. Observed pharmacophore features of, 12-crown-4 will not only
      help in designing new candidate drug molecules, which are specific to Abeta
      peptides but could also be used to design new imaging probe molecules, which
      could be used for labeling Abeta peptide.

PMID- 29200308
TI  - Dramatic Acceleration of an Acyl Transfer-Initiated Cascade by Using Electron
      Rich Amidine-Based Catalysts.
AB  - A tandem rearrangement of alpha,beta-unsaturated thioesters into tricyclic ene
      lactones fails with conventional amidine-based catalysts, but becomes possible
      when their electron-rich analogs are employed. A highly diastereo- and
      enantioselective version of this process has been developed using H-PIP 1b, a
      chiral catalyst prepared over a decade ago, but never utilized since its
      disclosure.

PMID- 29200309
TI  - Survival and mortality following TBI.
AB  - OBJECTIVES: Evaluation of life expectancy (LE) post traumatic brain injury (TBI)
      is important for planning services for patients and for dealing with medico-legal
      aspects. We hypothesized that LE for patients who survived 2 years post injury is
      equal to that of the general population (GP). METHODS: A cohort of 279 patients
      was assembled during a 5-year period and was followed for 22-27 years. During
      follow-up, 32 patients (11.5%) died, creating a huge censored data (88.5%).
      Analyses included standard mortality ratio (SMR), Kaplan-Meier method (KM), Cox
      proportional hazards regression analysis (PH) and calculations of life
      expectancy. RESULTS: About 77% of the patients were under 35 years of age at
      injury. This age cut-off point yielded differences for survival longevity by chi2
      tests (p < 0.0001), by KM analysis (p < 0.0001) and by Cox PH regression analysis
      (p < 0.0001, HR = 13.95). SMR for the entire cohort was 1.86. Shortening of LE in
      comparison with the GP is 3.58 years. Estimated shortening of LE by severity for
      mild, moderate and severe injury were -0.51, 4.11 and 13.77 years, respectively.
      CONCLUSIONS: Patients with mild TBI have a LE similar to the GP, and a reduction
      in LE was closely related to moderate and severe brain injury.

PMID- 29200310
TI  - Review: Amino acid concentration of high protein food products and an overview of
      the current methods used to determine protein quality.
AB  - Quality of the dietary protein in foods rather than amount of dietary protein may
      be of greater importance from a human health and wellness standpoint. Various
      systems are in place to determine the value of dietary protein. Protein
      digestibility-corrected amino acid score (PDCAAS) and digestible indispensable
      amino acid score (DIAAS) are the two major protein standards used to determine
      the completeness of proteins by their unique concentration and digestibility of
      indispensable amino acids. The purpose of this review was to provide a
      comprehensive comparison of the amino acid concentration of high protein foods
      and provide the current status of the use and practicality of the PDCAAS and
      DIAAS system. This review builds upon previous research analyzing the total
      nutrient density of protein-rich foods and expands scientific research
      investigating the quality of proteins. In summary, the average sum of
      indispensable amino acids for meat and fish products is much more consistent than
      that of non-meat and plant-based food products. However, some non-meat products
      have relatively similar amounts of indispensable amino acids on a similar serving
      size basis. The overwhelming aspect of determining protein quality is that
      greater research is needed to determine protein digestibility of food products.

PMID- 29200311
TI  - The development and release of maize fortified with provitamin A carotenoids in
      developing countries.
AB  - Micronutrient deficiencies have been identified as major public health problems
      affecting a large part of the world's population. Biofortification of staple
      crops like maize has been proposed as one of the most cost effective and feasible
      approaches to combat micronutrient deficiencies. Studies have shown that
      provitamin A from biofortified crops is highly bioavailable and has the capacity
      to improve vitamin A status of vulnerable groups. Most people in sub-Saharan
      Africa subsist on maize and many people may benefit from consumption of
      provitamin A carotenoid biofortified maize, especially women and children. With
      the exception of transgenic golden rice, biofortified crops have received
      considerable acceptance by most communities. Negative perceptions associated with
      yellow maize do not affect orange maize, which is, for example, well-liked in
      rural Zambia. With proper policy frameworks and full commercialization,
      provitamin A maize can address the problem of vitamin A deficiencies among poor
      nations with maize-based diets.

PMID- 29200312
TI  - Levels of circulating cortisol and cytokines in members of the Canadian Armed
      Forces: associations with age, sex, and anthropometry.
AB  - : This study assessed blood levels of cortisol and cytokines (inflammatory and
      non-inflammatory) in members of the regular Canadian Armed Forces (CAF), and
      examined the associations between sex, age, and adiposity and circulating levels
      of cortisol as well as pro- and anti-inflammatory cytokines. As part of a larger
      ranging project, 331 blood samples were collected from a representative
      population of the total CAF, which included officers and noncommissioned women
      and men from the Air Force, Navy, and Army. The blood samples were analyzed for
      levels of cortisol, C-reactive protein (CRP), adiponectin, and 20 cytokines
      (which included interleukins, interferons, and tumor necrosis factors). Higher
      levels of adiponectin were found in women compared with men (median and
      interquartile range; 16.71 (7.68-25.32) vs 5.81 (3.52-13.19) MUg/mL), and higher
      levels of interleukin (IL)-18 in men compared with women (89.25 (84.03-94.48) vs
      75.91 (69.70-82.13) pg/mL). An association between age and levels of stress and
      inflammatory cytokines was observed, with CRP, IL-18, IL-2 and adiponectin all
      increasing with increasing age. However, contrary to trends seen in the general
      population, cortisol levels decreased with increasing age. Levels of CRP and IL
      18 increased with an increase in adiposity, while adiponectin levels decreased.
      Most importantly, at the entire cohort level, a low detection rate for most of
      the cytokines was observed with 17 out of 22 cytokines having a detection below
      10%. IN CONCLUSION: In this CAF population, although an association between age
      and inflammatory cytokines was observed, both sex and adiposity had a small
      impact on levels of cortisol and cytokines.

PMID- 29200313
TI  - Effect of Single Nucleotide Polymorphisms in IGFBP2 and IGFBP3 Genes on Litter
      Size Traits in Berkshire Pigs.
AB  - Litter size is among the most important traits in swine breeding. However,
      information on the genetics of litter size in pigs is lacking. In this study, we
      identified single nucleotide polymorphisms (SNPs) in the insulin-like growth
      factor binding protein 2 and 3 (IGFBP2 and IGFBP3) genes in Berkshire pigs and
      analyzed their association with litter size traits. The IGFBP2 SNP was located on
      chromosome 15 intron 2 (455, A > T) and the IGFBP3 SNP was on chromosome 18
      intron 2 (53, A > G). The AT type of IGFBP2 and the GG type of IGFBP3 had the
      highest values for all litter size traits including total number born (TNB),
      number of pigs born alive, and breeding value according to TNB. Homozygous GG
      pigs expressed higher levels of IGFBP3 mRNA in the endometrium than pigs of other
      genotypes, and a positive correlation was observed between litter size traits and
      IGFBP3 but not IGFBP2 expression level. These results suggest that SNPs in the
      IGFBP2 and the IGFBP3 gene are useful biomarkers for increasing the reproductive
      productivity of Berkshire pigs.

PMID- 29200315
TI  - Psychosocial working conditions as determinants of asthma self-management at
      work: A systematic review.
AB  - OBJECTIVE: Asthma exerts a considerable impact on patients and their employers.
      While adequate self-management is able to improve patients' prognosis, its actual
      implementation in everyday life may depend on contextual factors. We aimed to
      review the literature on the potential determinants of asthma self-management at
      the workplace. DATA SOURCES: We systematically searched Medline and PsycINFO
      using terms related to the key concepts of interest (i.e., adult asthma, working
      conditions, and self-management). STUDY SELECTION: We included original studies
      published in peer-reviewed journals in English or German since 1992 addressing
      any type of asthma self-management behavior as the outcome and any type of
      working condition as the determinant. RESULTS: Upon implementation of a multi
      stage selection process, seven articles were included. As those studies showed
      considerable methodological heterogeneity, a qualitative analysis was applied. A
      first study identified three different adaptation profiles among employees with
      asthma with implications for self-management behavior. Another study suggested
      that concerns about taking time off from work may be associated with the
      utilization of emergency ambulance services for asthma. Five studies among
      workers with various chronic illnesses addressed determinants of self-disclosure,
      coping with acute symptoms (e.g., medication use at work), and the potential
      effect of practical and emotional support from line managers or colleagues on
      self-management. CONCLUSION: Our review indicates that the evidence for a
      potential link of occupational factors with asthma self-management at work is
      relatively sparse. Future research should take a more comprehensive approach by
      considering multiple types of working conditions and asthma self-management
      behaviors simultaneously.

PMID- 29200314
TI  - Assessment of structural and functional similarity of biosimilar products:
      Rituximab as a case study.
AB  - Biosimilars are products that are similar in terms of quality, safety, and
      efficacy to an already licensed reference/ innovator product and are expected to
      offer improved affordability. The most significant source of reduction in the
      cost of development of a biosimilar is the reduced clinical examination that it
      is expected to undergo as compared to the innovator product. However, this
      clinical relief is predicated on the assumption that there is analytical
      similarity between the biosimilar and the innovator product. As a result,
      establishing analytical similarity is arguably the most important step towards
      successful development of a biosimilar. Here, we present results from an
      analytical similarity exercise that was performed with five biosimilars of
      rituximab (Ristova(r), Roche), a chimeric mouse/ human monoclonal antibody
      biotherapeutic, that are available on the Indian market. The results show that,
      while the biosimilars exhibited similarity with respect to protein structure and
      function, there were significant differences with respect to size heterogeneity,
      charge heterogeneity and glycosylation pattern.

PMID- 29200316
TI  - Scientific, statistical, practical, and regulatory considerations in design space
      development.
AB  - The quality by design (QbD) paradigm guides the pharmaceutical industry towards
      improved understanding of products and processes, and at the same time
      facilitates a high degree of manufacturing and regulatory flexibility throughout
      the establishment of the design space. This review article presents scientific,
      statistical and regulatory considerations in design space development. All key
      development milestones, starting with planning, selection of factors,
      experimental execution, data analysis, model development and assessment,
      verification, and validation, and ending with design space submission, are
      presented and discussed. The focus is especially on frequently ignored topics,
      like management of factors and CQAs that will not be included in experimental
      design, evaluation of risk of failure on design space edges, or modeling scale-up
      strategy. Moreover, development of a design space that is independent of
      manufacturing scale is proposed as the preferred approach.

PMID- 29200317
TI  - Pediatric GIST presenting as anemia.
AB  - Gastrointestinal stromal tumors (GIST) are tumors of the gastrointestinal (GI)
      tract originating from the myenteric ganglion cells (interstitial cells of
      Cajal), that are very rare in children and adolescents. The most common clinical
      manifestation is acute or chronic, overt or occult GI bleeding although these
      tumors are asymptomatic in 10-30% of patients. We report a case of gastric GIST
      in a 11-year-old girl presenting with an iron deficiency refractory anemia
      without gastrointestinal symptoms and stool evidence of GI bleeding that caused a
      slight diagnostic delay.

PMID- 29200318
TI  - A simulation study on implementing marginal structural models in an observational
      study with switching medication based on a biomarker.
AB  - Assessing treatment effectiveness in longitudinal data can be complex when
      treatments are not randomly assigned and patients are allowed to switch treatment
      to other or no treatment, often in a manner that is driven by changes in one or
      more variables associated with patient or clinical characteristics. There can be
      confounding of the treatment effect from a time-varying variable, i.e., one which
      is affected by previous exposure and can in turn also influence subsequent
      treatment changes. Precision medicine relies on validated biomarkers to better
      classify patients by their probable response to treatment. However, biomarkers
      may be a source of time-varying confounding, which are affected by prior
      treatment in the evaluation and are also subject to measurement errors. The
      impact of switching medications based on a biomarker has received less attention.
      We conducted simulation studies to explore biased estimation under various
      scenarios when marginal structural model estimations are employed. Holding model
      misspecification issues constant, bias is severe in the presence of multiple
      switching, along with measurement error and missing data in the covariates.

PMID- 29200319
TI  - Mitochondrial C4375T mutation might be a molecular risk factor in a maternal
      Chinese hypertensive family under haplotype C.
AB  - Here, we reported a Han Chinese essential hypertensive pedigree based on clinical
      hereditary and molecular data. To know the molecular basis on this family,
      mitochondrial genome of one proband from the family was identified through direct
      sequencing analysis. The age of onset year and affected degree of patients are
      different in this family. And matrilineal family members carrying C4375T mutation
      and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is
      highly conservative in 17 species. It is suggested that these mutations might
      participate in the development of hypertension in this family. And halopgroup C
      might play a modifying role on the phenotype in this Chinese hypertensive family.

PMID- 29200320
TI  - Wiskott-Aldrich syndrome: Two case reports with a novel mutation.
AB  - BACKGROUND: The Wiskott-Aldrich syndrome (WAS) is X-linked recessive disorder
      associated with microplatelet thrombocytopenia, eczema, infections, and an
      increased risk of autoimmunity and lymphoid neoplasia. The originally described
      features of WAS include susceptibility to infections, microthrombocytopenia, and
      eczema. AIM: In this case report, we present our experience about two cases
      diagnosed with a new mutation. METHODS: We report phenotypical and laboratory
      description of two cases with WAS. RESULTS: We, for the first time, detected a
      new hemizygote mutation of WAS gene (NM_000377.2 p.M393lfs*102 (c.1178dupT)) in
      two patients. The first case was an 11-month-old boy presenting with complaints
      of recurrent soft tissue infection, ear infection, anemia, and thrombocytopenia
      with a low platelet volume. The second case was a 2-month-old boy presenting with
      thrombocytopenia and a low platelet volume. Both cases were the first-degree
      relatives: they were cousins and their mothers were sisters. CONCLUSION: Herein,
      we report two cases of WAS and a new gene mutation which would disrupt the WAS
      protein function within the Polyproline (PPP) domain. This report adds to the
      growing number of mutations which cause complex clinical manifestations
      associated with WAS.

PMID- 29200321
TI  - Two New Insertion/Deletion Variants of the PITX2 Gene and their Effects on Growth
      Traits in Sheep.
AB  - In China, Tong sheep (TS) and Lanzhou fat-tailed sheep (LFTS) are two closely
      relative endanger breeds for low meat production and low fecundity, finding some
      marker-assisted selected (MAS) is our first priority for improving their growth
      traits. For this purpose, Hu sheep (HS) and small-tailed Han sheep (STHS) were
      compared with two endangered breeds (TS and LFTS). Paired-liked homeodomain
      transcription factor 2 (PITX2) gene was the important member of PITX family,
      which could adjust animal growth through hypothalamic-pituitary-adrenal axis.
      During the past years, insertion/deletion (indel) has become increasingly popular
      in application as MAS. In this study, two novel indel loci were identified, and
      five significant differences, including chest width, hip width, chest depth,
      chest circumference, and body height, were found between different breeds.
      Interestingly, there was no DD genotype and smaller number of ID genotye. All the
      ID genotypes were significantly greater than II genotype, which was to say the
      allele of "D" was dominant variation and its frequency was lower, which
      demonstrated that it has huge space for selection. Briefly, the two indel were
      potential and useful DNA markers for selecting excellent individuals in relation
      to growth traits in sheep.

PMID- 29200322
TI  - Selecting analytical biomarkers for diagnostic applications: a first principles
      approach.
AB  - INTRODUCTION: Biomarkers are objective indications of a medical state that can be
      measured accurately and reproducibly. Traditional biomarkers enable diagnosis of
      disease through detection of disease-specific molecules, disease-mediated
      molecular changes, or distinct physiological or anatomical signatures. Areas
      covered: This work provides a framework for selecting biomarkers that are most
      likely to provide useful information about a patient's disease state. Though the
      authors emphasize markers related to disease, this work is also applicable to
      biomarkers for monitoring physiological changes such as ovulation or pregnancy.
      Additionally, the scope was restricted to biomarkers that are amenable to
      analytical detection across a range of health care levels, including low resource
      settings. The authors describe trade-offs between biomarkers'
      sensitivity/specificity for a disease-causing agent, the complexity of detection,
      and how this knowledge can be applied to the development of diagnostic tests.
      This report also details additional assessment criteria for successful tests.
      Expert commentary: Biomarker selection should primarily be driven by an attempt
      to answer an explicit clinical question (preferably causative relationship of the
      biomarker to disease-state), and only then by test development expediency (ease
      of detection). This framework is useful for stakeholders from test developers to
      clinicians to identify the trade-offs for diagnostic biomarkers for any use case.

PMID- 29200323
TI  - Refinements to light sources used to analyze the chloroplast cold-avoidance
      response over the past century.
AB  - Chloroplasts alter their subcellular positions in response to ambient light and
      temperature conditions. This well-characterized light-induced response, which was
      first described nearly 100 years ago, is regulated by the blue-light
      photoreceptor, phototropin. By contrast, the molecular mechanism of low
      temperature-induced chloroplast relocation (i.e., the cold-avoidance response)
      was unexplored until its discovery in the fern Adiantum capillus-veneris in 2008.
      Because this response is also regulated by phototropin, it was thought to occur
      in a blue light-dependent manner. However, until recently, the blue light
      dependency of this response could not be examined due to the lack of a stable
      light source under cold conditions. We recently refined the light source to
      precisely control light intensity under cold conditions. Using this light source,
      we observed the blue light dependency of the cold-avoidance response in the
      liverwort Marchantia polymorpha and the phototropin2-mediated cold-avoidance
      response in the flowering plant Arabidopsis thaliana. Thus, this mechanism is
      evolutionarily conserved among land plants.

PMID- 29200324
TI  - Breaking Down the Administrative Barriers: Condom Availability in the School
      Setting.
AB  - School nurses are at the forefront of health resource decisions, education, and
      health advocacy in the school setting. When it comes to sex education and condom
      availability, navigating the politics and controversy surrounding student access
      and education is not an easy task. Moreover, recent research shows school
      administrators are not aware of sexual health issues in their district and are
      not typically supportive of condom availability, limiting evidence-based practice
      implementation in the school setting. At the district level, school nurses must
      recognize these challenges and develop plans to promote science-based
      interventions for students' sexual health.

PMID- 29200325
TI  - Incidence and risk factors of bacterial and fungal infection during induction
      chemotherapy for high-risk neuroblastoma.
AB  - : High-risk neuroblastoma is an aggressive childhood cancer with poor outcomes.
      Treatment begins with an induction phase comprised of intense multi-agent
      chemotherapy with the goal of maximally reducing tumor bulk. Given the high
      intensity of induction chemotherapy, neutropenic fever and infectious
      complications are common; however, the actual incidence is difficult to determine
      from clinical trial reports. We performed a retrospective review of infection
      related complications in 76 children treated for high-risk neuroblastoma at Texas
      Children's Hospital. Medical records were reviewed for demographics, febrile
      neutropenia (FN) episodes, presence, and type of bacterial and fungal infections,
      and potential risk factors for infection. Fifty-seven percent of patients
      developed one or more serious bacterial or fungal infections during induction
      chemotherapy. Additionally, over 75% of patients had at least one admission for
      FN. Risk factors for developing any infection included female sex, MYCN
      amplification, and having Medicaid. Patients with external central venous
      catheters and those requiring parenteral nutrition had higher rates of bacteremia
      or fungemia. Each cycle, 50% were readmitted for either FN or infection. The
      overall burden of infectious complications was high, with 70% having two or more
      unplanned admissions for infection or FN. The incidence of febrile neutropenia
      and serious bacterial and fungal infections during induction chemotherapy for
      high-risk neuroblastoma is high. Most patients had at least two additional
      hospitalizations for infectious complications. Risk factors including female sex,
      MYCN amplification, payer status, and type of central access were associated with
      higher rates of infection in this cohort. ABBREVIATIONS: CLABSI Central line
      associated blood stream infection; CTCAE Common Terminology Criteria for Adverse
      Events; FN Febrile neutropenia; ANC Absolute neutrophil count; TPN Total
      parenteral nutrition.

PMID- 29200326
TI  - Probenecid directly impairs activation of the canine P2X7 receptor.
AB  - The current study aimed to determine if probenecid could directly impair the
      canine P2X7 receptor, a ligand-gated cation channel activated by extracellular
      adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that
      probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine
      P2X7. Flow cytometric measurements of ethidium+ uptake into HEK-293 cells
      expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation
      in a concentration-dependent manner, with a half maximal inhibitory concentration
      of 158 uM. Finally, ELISA measurements revealed that probenecid impairs ATP
      induced interleukin-1beta release in dog blood. In conclusion, this study reveals
      that probenecid can directly impair canine P2X7 activation.

PMID- 29200327
TI  - The Big Five Health Insurers' Membership And Revenue Trends: Implications For
      Public Policy.
AB  - The five largest US commercial health insurance companies together enroll 125
      million members, or 43 percent of the country's insured population. Over the past
      decade these insurers have become increasingly dependent for growth and
      profitability on public programs, according to an analysis of corporate reports.
      In 2016 Medicare and Medicaid accounted for nearly 60 percent of the companies'
      health care revenues and 20 percent of their comprehensive plan membership.
      Although headlines have focused on losses in the state Marketplaces created by
      the Affordable Care Act (ACA), the Marketplaces represent only a small fraction
      of insurers' members. Overall, the five largest insurers have remained profitable
      since passage of the ACA as a result of profits in other market segments.
      Notably, companies with significant Medicare or Medicaid enrollment have
      continued to insure beneficiaries in states where the insurers do not participate
      in Marketplaces. Given the insurers' dependence on public programs, there is
      potential to improve access if federal or state governments, or both, required
      insurers that participate in Medicare or Medicaid to also participate in the
      Marketplaces in the same geographic area. Such requirements could ensure more
      viable and less volatile insurance, benefiting people insured within each market
      as well as those who cycle on and off public and private insurance.

PMID- 29200329
TI  - Medical-Legal Partnerships At Veterans Affairs Medical Centers Improved Housing
      And Psychosocial Outcomes For Vets.
AB  - Medical-legal partnerships-collaborations between legal professionals and health
      care providers that help patients address civil legal problems that can affect
      health and well-being-have been implemented at several Veterans Affairs (VA)
      medical centers to serve homeless and low-income veterans with mental illness. We
      describe the outcomes of veterans who accessed legal services at four partnership
      sites in Connecticut and New York in the period 2014-16. The partnerships served
      950 veterans, who collectively had 1,384 legal issues; on average, the issues
      took 5.4 hours' worth of legal services to resolve. The most common problems were
      related to VA benefits, housing, family issues, and consumer issues. Among a
      subsample of 148 veterans who were followed for one year, we observed significant
      improvements in housing, income, and mental health. Veterans who received more
      partnership services showed greater improvements in housing and mental health
      than those who received fewer services, and those who achieved their predefined
      legal goals showed greater improvements in housing status and community
      integration than those who did not. Medical-legal partnerships represent an
      opportunity to expand cross-sector, community-based partnerships in the VA health
      care system to address social determinants of mental health.

PMID- 29200328
TI  - Medicare ACO Program Savings Not Tied To Preventable Hospitalizations Or
      Concentrated Among High-Risk Patients.
AB  - It has been widely assumed that better management and coordination of care for
      chronic conditions and high-risk patients would be the leading mechanisms for
      achieving savings in accountable care organizations (ACOs), specifically by
      reducing acute care needs through enhanced outpatient and preventive care. We
      examined the extent to which changes in spending and hospitalizations for ACO
      patients in the Medicare Shared Savings Program (MSSP) have been consistent with
      this expectation. By 2014, participation in the MSSP was associated with
      significant reductions in total Medicare fee-for-service spending for ACO
      patients but with proportionately smaller reductions in hospitalizations and some
      increases in hospitalizations for ambulatory care-sensitive conditions. In
      addition, spending reductions were not clearly concentrated among high-risk
      patients: Reductions for those patients accounted for only 38 percent of the
      total reduction among ACOs entering the MSSP in 2012, and reductions among 2013
      MSSP entrants were almost entirely concentrated among lower-risk patients. These
      findings suggest that, on average, care coordination and management efforts
      focused on ambulatory care-sensitive conditions and high-risk patients have not
      been the major drivers of early savings in the MSSP.

PMID- 29200330
TI  - The Uninsured Do Not Use The Emergency Department More-They Use Other Care Less.
AB  - There is a popular perception that insurance coverage will reduce overuse of the
      emergency department (ED). Both opponents and advocates of expanding insurance
      coverage under the Affordable Care Act (ACA) have made statements to the effect
      that EDs have been jammed with the uninsured and that paying for the uninsured
      population's emergency care has burdened the health care system as a result of
      the expense of that care. It has therefore been surprising to many to encounter
      evidence that insurance coverage increases ED use instead of decreasing it. Two
      facts may help explain this unexpected finding. First, there is a common
      misperception that the uninsured use the ED more than the insured. In fact,
      insured and uninsured adults use the ED at very similar rates and in very similar
      circumstances-and the uninsured use the ED substantially less than the Medicaid
      population. Second, while the uninsured do not use the ED more than the insured,
      they do use other types of care much less than the insured.

PMID- 29200331
TI  - Civil Rights Laws: The Authors Reply.

PMID- 29200332
TI  - Medicaid Expansion And Marketplace Eligibility Both Increased Coverage, With
      Trade-Offs In Access, Affordability.
AB  - Affordable Care Act (ACA) provisions implemented in 2014 provide a valuable case
      study regarding the merits of using public versus subsidized private insurance to
      help low-income people obtain and finance health care. In particular, nonelderly
      adults with incomes of 100-138 percent of the federal poverty level gained
      Medicaid eligibility if they lived in states that implemented the ACA's Medicaid
      expansion, whereas those in nonexpansion states became eligible for subsidized
      Marketplace coverage. Using data for 2008-15 from the National Health Interview
      Survey, we found that as of 2015, adults with family incomes in this range had
      experienced large declines in uninsurance rates in both expansion and
      nonexpansion states (the adjusted declines were 22 percentage points and 18
      percentage points, respectively). Adults in expansion and nonexpansion states
      also experienced similar increases in having a usual source of care and primary
      care visits, and similar reductions in delayed receipt of medical care due to
      cost. There were, however, important differences: Adults in expansion states
      experienced larger reductions in out-of-pocket spending but also faced greater
      difficulty accessing physician care relative to adults in nonexpansion states.

PMID- 29200333
TI  - The Promises And Pitfalls Of Treating Addiction.
AB  - Treatment of addiction in primary care should increase, but it will fail without
      the proper supports for providers in place.

PMID- 29200334
TI  - Performance And Participation Of Physicians In Year One Of Medicare's Value-Based
      Payment Modifier Program.
AB  - In 2015 Medicare launched the Physician Value-Based Payment Modifier program, the
      largest US ambulatory care pay-for-performance program to date and a precursor to
      the forthcoming Merit-based Incentive Payment System. In its first year, the
      program included practices with a hundred or more clinicians. We found that 1,010
      practices met this criterion, 899 of which had at least one attributed
      beneficiary. Of these latter practices, 263 (29.3 percent) failed to report
      performance data and received a 1 percent reporting-based penalty. Of the 636
      practices that reported performance data, those that elected quality tiering
      voluntarily receiving performance-based penalties or bonuses-and those with high
      use of electronic health records had better performance on quality and costs than
      other practices. Practices with a primary care focus had better quality than
      other practices but similar costs. These findings translated into differences in
      the receipt of penalties and bonuses and may have implications for performance
      patterns under the Merit-based Incentive Payment System.

PMID- 29200335
TI  - Rising Use Of Observation Care Among The Commercially Insured May Lead to Total
      And Out-Of-Pocket Cost Savings.
AB  - Proponents of hospital-based observation care argue that it has the potential to
      reduce health care spending and lengths-of-stay, compared to short-stay inpatient
      hospitalizations. However, critics have raised concerns about the out-of-pocket
      spending associated with observation care. Recent reports of high out-of-pocket
      spending among Medicare beneficiaries have received considerable media attention
      and have prompted direct policy changes. Despite the potential for changed
      policies to indirectly affect non-Medicare patients, little is known about the
      use of, and spending associated with, observation care among commercially insured
      populations. Using multipayer commercial claims for the period 2009-13, we
      evaluated utilization and spending among patients admitted for six conditions
      that are commonly managed with either observation care or short-stay
      hospitalizations. In our study period, the use of observation care increased
      relative to that of short-stay hospitalizations. Total and out-of-pocket spending
      were substantially lower for observation care, though both grew rapidly-and at
      rates much higher than spending in the inpatient setting-over the study period.
      Despite this growth, spending on observation care is unlikely to exceed spending
      for short-stay hospitalizations. As observation care attracts greater attention,
      policy makers should be aware that Medicare policies that disincentivize
      observation may have unintended financial impacts on non-Medicare populations,
      where observation care may be cost saving.

PMID- 29200336
TI  - Competition In Health Care: The Authors Reply.

PMID- 29200337
TI  - Competition In Health Care.

PMID- 29200338
TI  - ACA Open Enrollment Starts Amidst Tumult.
AB  - The Affordable Care Act continues to be buffeted by administration actions; a
      bipartisan market stabilization effort emerges in Congress.

PMID- 29200341
TI  - Health Disparities In Appalachia.

PMID- 29200340
TI  - Only One In Twenty Justice-Referred Adults In Specialty Treatment For Opioid Use
      Receive Methadone Or Buprenorphine.
AB  - People in the US criminal justice system experience high rates of opioid use
      disorder, overdose, and other adverse outcomes. Expanding treatment is a key
      strategy for addressing the opioid epidemic, but little is known about whether
      the criminal justice system refers people to the highest standard of treatment:
      the use of the opioid agonist therapies methadone or buprenorphine. We used 2014
      data from the national Treatment Episode Data Set to examine the use of agonist
      treatment among justice-involved people referred to specialty treatment for
      opioid use disorder. Only 4.6 percent of justice-referred clients received
      agonist treatment, compared to 40.9 percent of those referred by other sources.
      Of all criminal justice sources, courts and diversionary programs were least
      likely to refer people to agonist treatment. Our findings suggest that an
      opportunity is being missed to promote effective, evidence-based care for justice
      involved people who seek treatment for opioid use disorder.

PMID- 29200342
TI  - Disparities In Access: The Authors Reply.

PMID- 29200343
TI  - To Keep Patients, Some Physicians Get Creative.
AB  - In the face of growing competition, traditional practices have begun trying to
      guarantee same-day appointments.

PMID- 29200344
TI  - Reducing Disparities In Access To Health Care.

PMID- 29200345
TI  - Foundation Funding In Global Health.

PMID- 29200346
TI  - Public And Private Payments For Physician Office Visits.
AB  - We used data for 2014-15 from the Medical Expenditure Panel Survey to estimate
      standardized payments for nonelderly adults' physician office visits by type of
      insurance. Adults with public insurance, especially Medicaid, had substantially
      lower provider payments, out-of-pocket spending, and third-party payments than
      their peers with employer-sponsored or Marketplace insurance. Quantifying public
      private payment differences can help clarify choices for financing health care
      among low-income Americans.

PMID- 29200347
TI  - The Effect Of Medicaid On Medication Use Among Poor Adults: Evidence From Oregon.
AB  - Oregon's 2008 Medicaid expansion significantly increased the use of prescription
      medications in 2009-10.

PMID- 29200348
TI  - National Trends In Specialty Outpatient Mental Health Care Among Adults.
AB  - We examined national trends in the receipt of specialty outpatient mental health
      care, using data for 2008-15 from the National Survey on Drug Use and Health.
      Between 2008-09 and 2014-15 the number of US adults who received outpatient
      mental health care in the specialty sector rose from 11.3 million to 13.7 million
      per year, representing an increase from 5.0 percent to 5.7 percent of the adult
      population. Among those recipients, however, the annual weighted mean number of
      visits to the specialty sector remained unchanged. We found increases in both
      numbers and percentages of adults who received care within the specialty sector
      across age and sex groups and among non-Hispanic whites, people with Medicare,
      people with private health insurance, and people with family incomes of $20,000
      $49,999. Increases in receipt of specialty mental health care during 2012-15 may
      be related to recent policy initiatives aimed at reducing financial barriers to
      care.

PMID- 29200349
TI  - Mortality Quadrupled Among Opioid-Driven Hospitalizations, Notably Within Lower
      Income And Disabled White Populations.
AB  - Hospitals play an important role in caring for patients in the current opioid
      crisis, but data on the outcomes and composition of opioid-driven
      hospitalizations in the United States have been lacking. Nationally
      representative all-payer data for the period 1993-2014 from the National
      Inpatient Sample were used to compare the mortality rates and composition of
      hospitalizations with opioid-related primary diagnoses and those of
      hospitalizations for other drugs and for all other causes. Mortality among opioid
      driven hospitalizations increased from 0.43 percent before 2000 to 2.02 percent
      in 2014, an average increase of 0.12 percentage points per year relative to the
      mortality of hospitalizations due to other drugs-which was unchanged. While the
      total volume of opioid-driven hospitalizations remained relatively stable, it
      shifted from diagnoses mostly involving opioid dependence or abuse to those
      centered on opioid or heroin poisoning (the latter have higher case fatality
      rates). After 2000, hospitalizations for opioid/heroin poisoning grew by 0.01 per
      1,000 people per year, while hospitalizations for opioid dependence or abuse
      declined by 0.01 per 1,000 people per year. Patients admitted for opioid/heroin
      poisoning were more likely to be white, ages 50-64, Medicare beneficiaries with
      disabilities, and residents of lower-income areas. As the United States combats
      the opioid epidemic, efforts to help hospitals respond to the increasing severity
      of opioid intoxication are needed, especially in vulnerable populations.

PMID- 29200352
TI  - Behavioral Health, Provider Payment, And More.

PMID- 29200351
TI  - Risk Adjustment May Lessen Penalties On Hospitals Treating Complex Cardiac
      Patients Under Medicare's Bundled Payments.
AB  - To reduce variation in spending, Medicare has considered implementing a cardiac
      bundled payment program for acute myocardial infarction and coronary artery
      bypass graft. Because the proposed program does not account for patient risk
      factors when calculating hospital penalties or rewards ("reconciliation
      payments"), it might unfairly penalize certain hospitals. We estimated the impact
      of adjusting for patients' medical complexity and social risk on reconciliation
      payments for Medicare beneficiaries hospitalized for the two conditions in the
      period 2011-13. Average spending per episode was $29,394. Accounting for medical
      complexity substantially narrowed the gap in reconciliation payments between
      hospitals with high medical severity (from a penalty of $1,809 to one of $820, or
      a net reduction of $989), safety-net hospitals (from a penalty of $217 to one of
      $87, a reduction of $130), and minority-serving hospitals (from a penalty of $70
      to a reward of $56, an improvement of $126) and their counterparts. Accounting
      for social risk alone narrowed these gaps but had minimal incremental effects
      after medical complexity was accounted for. Risk adjustment may preserve
      incentives to care for patients with complex conditions under Medicare bundled
      payment programs.

PMID- 29200350
TI  - Value Of Waiving Coinsurance For Colorectal Cancer Screening In Medicare
      Beneficiaries.
AB  - Financial barriers to colorectal cancer screening persist despite the Affordable
      Care Act (ACA). Medicare beneficiaries may face 20 percent coinsurance for a
      screening colonoscopy when the procedure includes the removal of polyps or
      follows a positive fecal screening test. Using an established microsimulation
      model, we estimated that waiving this coinsurance would result in 1.7 fewer
      colorectal cancer deaths (a decrease of 13 percent) and $17,000 higher colorectal
      cancer-related costs (an increase of 0.6 percent) for the Centers for Medicare
      and Medicaid Services per 1,000 sixty-five-year-olds, assuming a 10-percentage
      point increase in the rates of first colonoscopy screening, follow-up, and
      surveillance. If the rates did not change, waiving coinsurance would increase
      total costs by $51,000 (1.9 percent) per 1,000 sixty-five-year-olds. Estimated
      screening benefits were comparable when fecal testing was assumed to be the
      primary screening method. Moreover, waiving coinsurance would be cost-effective
      if the screening rate increased by 0.6 percentage points, assuming a willingness
      to-pay threshold of $50,000 per quality-adjusted life-year gained. Thus, the
      waiver is likely to have a favorable balance of health and cost impact.

PMID- 29200353
TI  - Precision Response Needed For HIV/AIDS.

PMID- 29200355
TI  - Comparing The Effects Of Reference Pricing And Centers-Of-Excellence Approaches
      To Value-Based Benefit Design.
AB  - Various health insurance benefit designs based on value-based purchasing have
      been promoted to steer patients to high-value providers, but little is known
      about the designs' relative effectiveness and underlying mechanisms. We compared
      the impact of two designs implemented by the California Public Employees'
      Retirement System on inpatient hospital total hip or knee replacement: a
      reference-based pricing design for preferred provider organizations (PPOs) and a
      centers-of-excellence design for health maintenance organizations (HMOs). Payment
      and utilization data for the procedures in the period 2008-13 were evaluated
      using pre-post and quasi-experimental designs at the system and health plan
      levels, adjusting for demographic characteristics, case-mix, and other
      confounders. We found that both designs prompted higher use of designated low
      price high-quality facilities and reduced average replacement expenses per member
      at the plan and system levels. However, the designs used different routes: The
      reference-based pricing design reduced average replacement payments per case in
      PPOs by 26.7 percent in the first year, compared to HMOs, but did not lower PPO
      members' utilization rates. In contrast, the centers-of-excellence design lowered
      HMO members' utilization rates by 29.2 percent in the first year, compared to
      PPOs, but did not reduce HMO average replacement payments per case. The reference
      based pricing design appears more suitable for reducing price variation, and the
      centers-of-excellence design for addressing variation in use.

PMID- 29200354
TI  - Hepatitis C Testing Increased Among Baby Boomers Following The 2012 Change To CDC
      Testing Recommendations.
AB  - In 2012 the Centers for Disease Control and Prevention recommended routine
      testing for hepatitis C for people born in the period 1945-65. Until now, the
      recommendation's impact on hepatitis C screening rates in the United States has
      not been fully understood. We used an interrupted time series with comparison
      group design to analyze hepatitis C screening rates in the period 2010-14 among
      2.8 million commercially insured adults in the MarketScan database. Hepatitis C
      screening rates increased yearly between 2010 and 2014, from 1.65 to 2.59 per 100
      person-years. A 49 percent increase in screening rates among people born during
      1945-65 followed the release of the recommendation, but no such increase was
      observed among adults born after 1965. The effect among the target population was
      sustained, and by twenty-four months after the recommendation's release,
      screening rates had increased 106 percent. We conclude that the hepatitis C
      testing policy change resulted in significantly increased testing among the
      target population and may have decreased the magnitude of the hepatitis C
      epidemic.

PMID- 29200356
TI  - Marketplace Plans Provide Risk Protection, But Actuarial Values Overstate
      Realized Coverage For Most Enrollees.
AB  - The Affordable Care Act (ACA) has increased the number of Americans with health
      insurance. Yet many policy makers and consumers have questioned the value of
      Marketplace plan coverage because of the generally high levels of cost sharing.
      We simulated out-of-pocket spending for bronze, silver, or gold Marketplace plans
      (those having actuarial values of 60 percent, 70 percent, and 80 percent,
      respectively). We found that for the vast majority of consumers, the proportion
      of covered spending paid by the plans is likely to be far less than their
      actuarial values, the metric commonly used to convey plan generosity. Indeed,
      only when annual health care spending exceeds $16,500 for bronze plans, $19,500
      for silver plans, and $21,500 for gold plans do plans in these metal tiers cover
      the proportion of costs matching their actuarial values. While Marketplace plans
      substantially reduce consumers' exposure to financial risk relative to being
      uninsured, the use of actuarial values to communicate plan generosity is likely
      to be misleading to consumers.

PMID- 29200357
TI  - The US Provided $13 Billion In Development Assistance For Health In 2016, Less
      Per Person Than Many Peer Nations.
AB  - Despite dramatic growth between 1990 and 2010, development assistance for health
      from high-income countries and development agencies to low- and middle-income
      countries has stagnated, and proposed cuts make future funding uncertain. To
      further understand international financial flows for health, we examined
      international contributions from major donor countries. Our findings showed that
      the United States provided more development assistance for health than any other
      country, but it provided less than others relative to national population,
      government spending, and income. Norway, Denmark, Luxembourg, and the United
      Kingdom stand out when the provision of health assistance is considered relative
      to these other factors. Seventeen of twenty-three countries did not reach a
      target that corresponds to an international goal. If all twenty-three countries
      had reached this goal, an additional $13.3 billion would have been available for
      global health in 2016. Systematic efforts are needed to encourage countries to
      meet these targets. Sustained health improvement in low- and middle-income
      countries will benefit greatly from ongoing international support.

PMID- 29200359
TI  - Transgender Patients And Health Care Providers.

PMID- 29200360
TI  - Health Inequity And Civil Rights Laws.

PMID- 29200361
TI  - Among-Individual Variation in Desert Iguanas (Squamata: Dipsosaurus dorsalis):
      Endurance Capacity Is Positively Related to Home Range Size.
AB  - Among species of lizards, endurance capacity measured on a motorized treadmill is
      positively related to daily movement distance and time spent moving, but few
      studies have addressed such relationships at the level of individual variation
      within a sex and age category in a single population. Both endurance capacity and
      home range size show substantial individual variation in lizards, rendering them
      suitable for such studies. We predicted that these traits would be positively
      related because endurance capacity is one of the factors that has the potential
      to limit home range size. We measured the endurance capacity and home range size
      of adult male desert iguanas (Dipsosaurus dorsalis). Lizards were field captured
      for measurements of endurance, and home range data were gathered using visual
      identification of previously marked individuals. Endurance was significantly
      repeatable between replicate trials, conducted 1-17 d apart ([Formula: see text]
      for log-transformed values, [Formula: see text], [Formula: see text]). The log of
      the higher of two endurance trials was positively but not significantly related
      to log body mass. The log of home range area was positively but not significantly
      related to log body mass, the number of sightings, or the time span from first to
      last sighting. As predicted, log endurance was positively correlated with log
      home range area ([Formula: see text], [Formula: see text], one-tailed [Formula:
      see text]; for body-mass residual endurance values: [Formula: see text], one
      tailed [Formula: see text]). These results suggest that endurance capacity may
      have a permissive effect on home range size. Alternatively, individuals with
      larger home ranges may experience training effects (phenotypic plasticity) that
      increase their endurance.

PMID- 29200363
TI  - Have Our Sterility Practices Kept Up With the Tremendous Advances in Sedation and
      Surgical Techniques?

PMID- 29200362
TI  - Psychronectria hyperantarctica, gen. nov., comb. nov., epitypification and
      phylogenetic position of an Antarctic bryophilous ascomycete.
AB  - The holotype of Thyronectria hyperantarctica was re-examined, redescribed, and
      compared with new collections of an Antarctic bryophilous ascomycete from a
      similar area. Because the condition of type material was insufficient for
      molecular studies, the authors designated an epitype from newly collected
      material with a high degree of morphological similarity to the holotype and
      paratype material. Phylogenetic analysis of the epitype revealed that its closest
      phylogenetic affinity was with the family Tilachlidiaceae and it formed a
      monophyletic group in this lineage within other collections of the species.
      Therefore, the new monotypic genus Psychronectria is described to accommodate
      Thyronectria hyperantarctica. The fungus is superficially similar to Thyronectria
      species in Nectriaceae, but the ascospores differ in color, size, and type of
      septation.

PMID- 29200366
TI  - A Combination of Dexmedetomidine and Lidocaine Is a Cardiovascularly Safe Dental
      Local Anesthetic for Hypertensive Rats Treated With a Nonselective beta
      Adrenergic Antagonist.
AB  - Hypertensive patients receiving nonselective beta-adrenergic antagonists are
      vulnerable to hypertension and bradycardia when injected with dental local
      anesthetic formulations containing epinephrine. Dexmedetomidine (DEX), an alpha2
      adrenergic agonist, has been reported to prolong and enhance the local anesthetic
      effects of lidocaine. The cardiovascular effects of the DEX-lidocaine combination
      have not yet been investigated in the presence of nonselective beta-adrenergic
      antagonists. Therefore, we assessed the cardiovascular effects of the DEX
      lidocaine combination in spontaneously hypertensive rats (SHR) treated with a
      nonselective beta-adrenergic antagonist (propranolol). We injected propranolol
      treated rats with various concentrations of DEX alone, 100 MUg/kg epinephrine
      alone, or 5 MUg/kg DEX combined with 2% lidocaine and measured their blood
      pressure (BP) and heart rates (HR) to assess the cardiovascular effects. The BP
      of propranolol-treated SHR was significantly increased by treatment with 100
      MUg/kg epinephrine alone. The BP and HR of propranolol-treated SHR were not
      significantly changed by treatment with low concentrations of DEX, but they were
      significantly decreased by treatment with a high concentration of DEX (50
      MUg/kg). Moreover, there was no significant difference in the BP and HR of
      propranolol-treated SHR after the injection of a combination of 5 MUg/kg DEX and
      2% lidocaine. Thus, the DEX-lidocaine combination may be an acceptable addition
      to dental local anesthetic solutions from a cardiovascular standpoint for
      hypertensive patients receiving nonselective beta-adrenergic antagonists.

PMID- 29200367
TI  - Anesthetic Management in Mitochondrial Encephalomyopathy: A Case Report.
AB  - We report on a morbidly obese 16-year-old boy (weight, 116 kg; height, 176 cm;
      body mass index, 35.5 kg/m2) with mitochondrial encephalomyopathy and a history
      of cerebral infarction, epilepsy, and severe mental retardation. The patient was
      scheduled for elective surgery under general anesthesia for multiple dental
      caries and entropion of the left eye. Preoperative examination results, including
      an electrocardiogram, were normal. No obvious cardiac function abnormalities were
      observed on echocardiography. Midazolam (10 mg) was administered orally as
      premedication 30 minutes before transfer to the operating room; however, the
      patient was uncooperative, and his body movements were difficult to control upon
      entering the operating room. This complicated our attempts to establish a
      peripheral intravenous line and necessitated volatile inhalational induction,
      followed by maintenance using total intravenous anesthesia. General anesthesia
      was used to minimize metabolic system stress. We did not use an infusion solution
      containing sodium lactate. The operation and subsequent clinical course until
      discharge were uneventful. Because aerobic metabolism is already compromised in
      patients with mitochondrial encephalomyopathy, anesthetic management should be
      designed to avoid placing additional stress on the metabolic system.

PMID- 29200368
TI  - Influence of Fasting Duration on Body Fluid and Hemodynamics.
AB  - Fasting before general anesthesia aims to reduce the volume and acidity of
      stomach contents, which reduces the risk of regurgitation and aspiration.
      Prolonged fasting for many hours prior to surgery could lead to unstable
      hemodynamics, however. Therefore, preoperative oral intake of clear fluids 2
      hours prior to surgery is recommended to decrease dehydration without an increase
      in aspiration risk. In this study, we investigated the body fluid composition and
      hemodynamics of patients undergoing general anesthesia as the first case of the
      day versus the second subsequent case. We retrospectively reviewed the general
      anesthesia records of patients over 20 years old who underwent oral maxillofacial
      surgery. We investigated patient demographics, preoperative fasting time,
      anesthetic time, urine output, infusion volume, and opioid and vasopressor use.
      With respect to body fluid and hemodynamics, we extracted the data from the
      induction of anesthesia through 2 hours of anesthesia time. Thirty patients were
      suitable for this study. Patients were divided into 2 groups: patients who
      underwent surgery as the first case of the day (am group: n = 15) and patients
      who underwent surgery as the second case (pm group: n = 15). There were no
      significant differences between the 2 groups in patient demographics. In the pm
      group, fasting time for a light meal (832 minutes) was significantly longer than
      for the am group (685 minutes), p = .005. In the pm group, fasting time for clear
      fluids (216 minutes) was also significantly longer than for the am group (194
      minutes), p = .005. Body fluid composition was not significantly different
      between the 2 groups. In addition, cardiac parameters intraoperatively were
      stable. In the pm group, vasopressors were used in 4 patients at the induction of
      anesthesia (p = .01). There were not statistically significant changes in cardiac
      function or body fluid composition between patients treated as the first case of
      the day vs patients who underwent surgery with general anesthesia as the second
      case of the day.

PMID- 29200369
TI  - Anesthetic Management of a Patient With a History of Rhabdomyolysis for Dental
      Treatment.
AB  - When general anesthesia is administered for patients considered at high risk for
      rhabdomyolysis, appropriate precautions are warranted. The use of suitable
      anesthetics, with attention to intravenous fluid management, electrolyte balance,
      respiration, and metabolism, should be addressed. We performed general anesthesia
      for dental treatment and biopsy for fibrous hyperplasia of the buccal mucosa in a
      patient with a history of rhabdomyolysis. We utilized thiamylal sodium,
      midazolam, rocuronium bromide, nitrous oxide, fentanyl, and remifentanil without
      using volatile anesthetics and propofol for this case. No complications of
      rhabdomyolysis were noted.

PMID- 29200370
TI  - Anesthesia for a Patient With Excessive Supragastric Belching.
AB  - Excessive supragastric belching is rarely described in the anesthesia literature.
      Anesthesia planning of a 26-year-old patient with excessive supragastric
      belching, history of superior mesenteric artery syndrome (SMAS), and dental
      anxiety requires preoperative assessment. This case report outlines the
      anesthetic considerations and the management to facilitate comprehensive
      dentistry. Key anesthetic considerations include anxiolysis, aspiration risk
      reduction, total intravenous anesthesia (TIVA), and postoperative nausea and
      vomiting (PONV) prophylaxis.

PMID- 29200371
TI  - Comparison of Anesthesia for Dental/Oral Surgery by Office-based Dentist
      Anesthesiologists versus Operating Room-based Physician Anesthesiologists.
AB  - Few studies have examined the practice characteristics of dentist
      anesthesiologists and compared them to other anesthesia providers. Using outcomes
      from the National Anesthesia Clinical Outcomes Registry and the Society for
      Ambulatory Anesthesia Clinical Outcomes Registry for dental/oral surgery
      procedures, we compared 7133 predominantly office-based anesthetics by dentist
      anesthesiologists to 106,420 predominantly operating room anesthetics performed
      by physician anesthesia providers. These encounters were contrasted with 34,191
      previously published encounters from the practices of oral and maxillofacial
      surgeons. Children younger than 6 years received the greatest proportion of
      general anesthetic services rendered by both dentist anesthesiologists and
      hospital-based anesthesia providers. These general anesthesia services were
      primarily provided for complete dental rehabilitation for early childhood caries.
      Overall treatment time for complete dental rehabilitation in the office-based
      setting by dentist anesthesiologists was significantly shorter than comparable
      care provided in the hospital operating room and surgery centers. The anesthesia
      care provided by dentist anesthesiologists was found to be separate and distinct
      from anesthesia care provided by oral and maxillofacial surgeons, which was
      primarily administered to adults for very brief surgical procedures. Cases
      performed by dentist anesthesiologists and hospital-based anesthesia providers
      were for much younger patients and of significantly longer duration when compared
      with anesthesia administered by oral and maxillofacial surgeons. Despite the
      limited descriptive power of the current registries, office-based anesthesia
      rendered by dentist anesthesiologists is clearly a unique and efficient mode of
      anesthesia care for dentistry.

PMID- 29200372
TI  - Anesthetic Efficacy of Articaine and Lidocaine in a Primary Intraseptal
      Injection: A Prospective, Randomized Double-Blind Study.
AB  - Additional studies are needed to evaluate intraseptal anesthesia in the
      mandibular first molar. The purpose of this study was to compare the anesthetic
      efficacy of a primary intraseptal injection of articaine and lidocaine,
      administered with a computer-controlled local anesthetic delivery (CCLAD) system,
      in asymptomatic mandibular first molars. Using a crossover design, 100 subjects
      randomly received intraseptal injections of 1.4 mL of 4% articaine and 2%
      lidocaine, both with 1:100,000 epinephrine, at 2 separate appointments.
      Injections were given in the interdental papillae, mesial (0.7 mL) and distal
      (0.7 mL) to the first molar. An electric pulp tester was used to test for pulpal
      anesthesia. Pain of injection, postoperative pain, and pulse rate were also
      evaluated. Data were statistically analyzed. Anesthetic success rate for the
      mandibular first molar was 32% for articaine and 30% for lidocaine, with no
      statistically significant difference (p = .8689) between the two. No significant
      differences were found between formulations for pain of injection. The
      intraseptal injection did not cause a clinically meaningful increase in pulse
      rate. Postoperative pain decreased each day with no significant differences
      between formulations. In conclusion, a primary intraseptal injection does not
      achieve a high success rate of pulpal anesthesia in the mandibular first molar.

PMID- 29200373
TI  - Retropharyngeal Dissection by Parker Flex-Tip Nasal Endotracheal Tube.
AB  - Possible complications of nasotracheal intubation include injury to the nasal or
      pharyngeal mucosa. Dissection of the retropharyngeal tissue by the endotracheal
      tube is one of the rarer of the more severe complications. Previous studies have
      indicated that the Parker Flex-Tip (PFT) tracheal tube (Parker Medical, Highlands
      Ranch, Colo) reduces the incidence of mucosal injury. We experienced a case
      involving inadvertent retropharyngeal placement of a PFT tube in a 29-year-old
      patient during nasotracheal intubation under general anesthesia for elective
      dental treatment. Despite thermosoftening the PFT tube, expanding the nasal
      meatus, and ensuring gentle maneuvering, the tube intruded into the left
      retropharyngeal mucosa. However, the injury was not severe, and the only required
      treatment was the administration of antibiotics and corticosteroids. Even when a
      PFT tube is utilized, pharyngeal dissection is possible. When resistance is felt
      during passing of the PFT tube through the nasopharynx, an alternative method to
      overcome this resistance should be utilized.

PMID- 29200374
TI  - Dexmedetomidine Increases the Latency of Thermal Antinociception in Rats.
AB  - Recent reports have stated that dexmedetomidine (DEX), an alpha2-adrenoreceptor
      agonist, enhances the local anesthetic effects of ropivacaine and prolongs its
      effective duration. However, little is known about the effect of a combination of
      DEX and lidocaine on anesthetic duration. Therefore, we investigated whether DEX
      can prolong the local anesthetic effect of lidocaine, using the thermal paw
      withdrawal test in Wistar rats in order to measure local anesthetic duration. We
      subcutaneously injected 50 MUL of either normal saline, 2% lidocaine, a
      combination of 0.5 MUg/kg DEX and 2% lidocaine, or a combination of 2% lidocaine
      with 1:80,000 epinephrine into the plantar surface of the left hind paw of the
      rats. The plantar region was stimulated using heat. We measured the perceived
      acute pain according to paw movement in response to stimulation. We found DEX
      significantly prolonged the paw withdrawal latency of lidocaine. Moreover, we
      found that DEX can prolong the local anesthetic duration of lidocaine as much as
      1:80,000 epinephrine, up to 35 minutes after injection. In conclusion, this study
      concluded that a combination of DEX and lidocaine may be useful as a local
      anesthetic, similar to a combination of epinephrine and lidocaine, for short
      procedures.

PMID- 29200375
TI  - A Case of Laryngeal Granuloma Likely Caused by Laryngopharyngeal Reflux Disease
      Following a Sagittal Split Ramus Osteotomy.
AB  - Laryngeal granuloma is an uncommon complication of prolonged endotracheal
      intubation. A 25-year-old woman with severe jaw deformity underwent sagittal
      split ramus osteotomy under general anesthesia. Two days after extubation, the
      patient complained of hoarseness, sore throat, and dyspnea. When symptoms
      persisted, she was evaluated in the Otolaryngology Department. She was diagnosed
      with laryngeal granuloma of the bilateral arytenoid cartilages, and conservative
      treatment was selected. Administration of corticosteroid hormones, proton pump
      inhibitors, and a subsequent follow-up examination performed in our outpatient
      clinic showed no evidence of recurrence 10 months after the initial presentation.

PMID- 29200377
TI  - Comparison of the CAS-POL and IOM samplers for determining the knockdown
      efficiencies of water sprays on float coal dust.
AB  - Float coal dust, generated by mining operations, is distributed throughout mine
      airways by ventilating air designed to purge gases and respirable dust. Float
      coal dust poses an explosion hazard in the event of a methane ignition. Current
      regulation requires the application of inert rock dust in areas subjected to
      float coal dust in order to mitigate the hazard. An alternate method using water
      sprays, which have been effective in controlling respirable dust hazards, has
      been proposed as a way to control float coal dust generated on longwall faces.
      However, the knockdown efficiency of the proposed water sprays on float coal dust
      needs to be verified. This study used gravimetric isokinetic Institute of
      Occupational Medicine (IOM) samplers alongside a real-time aerosol monitor (Cloud
      Aerosol Spectrometer with polarization; CAS-POL) to study the effects of spray
      type, operating pressure, and spray orientation on knockdown efficiencies for
      seven different water sprays. Because the CAS-POL has not been used to study
      mining dust, the CAS-POL measurements were validated with respect to the IOM
      samplers. This study found that the CAS-POL was able to resolve the same trends
      measured by the IOM samplers, while providing additional knockdown information
      for specific particle size ranges and locations in the test area. In addition,
      the CAS-POL data was not prone to the same process errors, which may occur due to
      the handling of the IOM filter media, and was able to provide a faster analysis
      of the data after testing. This study also determined that pressure was the
      leading design criteria influencing spray knockdown efficiency, with spray type
      also having some effect and orientation having little to no effect. The results
      of this study will be used to design future full-scale float coal dust capture
      tests involving multiple sprays, which will be evaluated using the CAS-POL.

PMID- 29200376
TI  - Anesthetic Considerations for Patients on Antidepressant Therapy-Part I.
AB  - Millions of patients take antidepressant medications in the United States for the
      treatment of depression or anxiety disorders. Some antidepressants are prescribed
      off-label to treat problems such as chronic pain, low energy, and menstrual
      symptoms. Antidepressants are a broad and expansive group of medications, but the
      more common drug classes include tricyclic antidepressants, selective serotonin
      reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine
      oxidase inhibitors. A miscellaneous or "atypical" category covers other agents.
      Some herbal supplements that claim to have antidepressant activity will also be
      discussed. In Part I of this review, antidepressant pharmacology, adverse
      effects, and drug interactions with adrenergic agonists will be discussed. In
      part II, drug interactions with sedation and general anesthetics will be
      reviewed. Bleeding effects and serotonin syndrome implications in anesthetic
      practice will also be highlighted.

PMID- 29200378
TI  - Evaluating hearing loss risks in the mining industry through MSHA citations.
AB  - A new noise regulation for the mining industry became effective in 2000,
      providing a consistent regulatory requirement for both coal and non-coal mining
      divisions. The new rule required mines to implement hearing conservation
      programs, including a system of continuous noise monitoring, provision of hearing
      protection devices, audiometric testing, hearing loss training, and record
      keeping. The goal of this study was to assess hearing conservation program
      compliance, and excessive noise exposure and hearing loss risks for both coal and
      non-coal mining divisions through evaluating MSHA citations. We analyzed 13,446
      MSHA citations from 2000-2014 pertinent to 30 CFR Part 62. Descriptive statistics
      were generated and comparisons were made among mines of different commodities. In
      addition, one-way ANOVA on ranks was conducted to estimate the correlation
      between excess risks and establishment size. Results showed that 25.6% of coal
      mines and 14.7% of non-coal mines were cited at least once during this period of
      time. Larger numbers of noncompliance were seen in stone, sand, and gravel mines
      (SSG). Results also suggested inadequate efforts in both audiometric testing and
      minimizing risk after excessive noise exposure. Finally, establishment size of
      mine was correlated with the increasing risk of noncompliance. We anticipate that
      this study can guide resource allocation for preventing noise-induced hearing
      loss, and help improve risk management in mining.

PMID- 29200379
TI  - Gender differences in psychosocial predictors of self-perceived health status in
      the elderly: Evidence from a Brazilian community study.
AB  - This article aims to identify the psychosocial factors associated with self
      perceived health status in the Brazilian elderly population and to present
      differences related to gender. The data were collected by questionnaire,
      including sociodemographic and behavioral questions, and scales for psychological
      dimensions. Self-perceived health status is related to level of education,
      physical activity, and self-efficacy in the total population. Regarding gender
      differences, self-rated health status among men is related to education level and
      self-efficacy and in women to level of education, physical activity, social
      support, and self-efficacy. These results can inform future health promotion
      interventions.

PMID- 29200381
TI  - Editorial: The Aging Male: Physiology, Pathophysiology, and Therapeutic
      Perspectives.

PMID- 29200380
TI  - Notes on Amanita section Caesareae from Malaysia.
AB  - Some Amanita specimens collected from Malaysia are critically investigated by
      morphological examination and molecular analysis of two gene fragments, the nuc
      rDNA partial 28S (28S) gene and the internal transcriber spacer (ITS1-5.8S-ITS2 =
      ITS) regions. Six phylogenetic species of Amanita section Caesareae are
      recognized among the studied collections. One of them is described as new, A.
      malayensis. Four of the phylogenetic species correspond with existing morphology
      based taxa: A. aporema, A. javanica, A. princeps, and A. similis. The remaining
      species is not described because of the paucity of material. Detailed
      descriptions and the distribution of these southeastern Asian species are
      provided, along with a key to the species of section Caesareae from Malaysia.

PMID- 29200382
TI  - [For a proper use of scepticism towards sciences].

PMID- 29200383
TI  - [Rabies virus induces the formation of stress granules, which are in close
      proximity to viral factories].

PMID- 29200384
TI  - [From cyclops to reality: a fresh look at the genetics of holoprosencephaly].

PMID- 29200385
TI  - [The CD8+ T cell innate function in the war against cancer].

PMID- 29200386
TI  - [Copy-number analysis identifies new prognostic marker in acute myeloid
      leukemia].

PMID- 29200387
TI  - [Jumping-to-conclusions in schizophrenia is mediated by circular inference].

PMID- 29200388
TI  - [Triple-negative breast cancer therapy via nectin-4 targeting].

PMID- 29200389
TI  - [Circulating exosomal microRNA as biomarkers in mutiple myeloma].

PMID- 29200390
TI  - [Endocytosis in dendrites: a local tool to regulate synaptic transmission].

PMID- 29200391
TI  - [Gal-9 promotes viral persistence of hepatitis virus in the liver].

PMID- 29200392
TI  - [When germs get involved in Parkinson's disease].

PMID- 29200393
TI  - [Skeletal muscle aging and mitochondrial dysfunction: an update].
AB  - One of the most obvious and deleterious changes occurring with aging is a
      progressive loss of skeletal muscle mass and strength, a physiological process
      named sarcopenia. Amongst the multiple theories that have been put forward to
      explain sarcopenia, the mitochondrial theory of aging, which postulates that the
      accumulation of mitochondrial dysfunctions with aging plays a causal role in
      muscle atrophy, has focused intense research effort and attention in the past
      decades. The generally accepted view of this theory is that, due to the reactive
      oxygen species (ROS) production inherent to respiratory chain activity, oxidative
      damage to mitochondrial proteins, lipids and DNA accumulates with aging. This
      damage is thought to (i) exacerbate mitochondrial ROS production, (ii) impair the
      capacity of mitochondria to adequately match the cellular ATP demand and (iii)
      trigger mitochondrial-mediated apoptosis. Although very appealing, this theory
      remains controversial. The aims of the present review are (i) to provide the
      reader with a short, but comprehensive review of the current literature linking
      mitochondrial dysfunction and sarcopenia and (ii) to briefly discuss the
      potential mechanisms underlying the accumulation of mitochondrial dysfunction
      with muscle aging.

PMID- 29200394
TI  - [The IgH 3'RR: Doctor Jekyll and Mister Hyde of B-cell maturation and
      lymphomagenesis].
AB  - The four transcriptional enhancers located in the 3' regulatory region (3'RR) of
      the IgH locus control the late phases of B-cell maturation, namely IgH locus
      transcription, somatic hypermutation and class switch recombination. Doctor
      Jekyll by nature, the 3'RR acts as Mister Hyde in case of oncogenic translocation
      at the IgH locus taking under its transcriptional control the translocated
      oncogene. The aim of this review is to show this duality on the basis of the
      latest scientific advances in the structure and function of the 3'RR and to
      hIghlight the targeting of the 3'RR as a potential therapeutic approach in mature
      B-cell lymphomas.

PMID- 29200395
TI  - [The future of forensic DNA analysis for criminal justice].
AB  - In the criminal framework, the analysis of approximately 20 DNA microsatellites
      enables the establishment of a genetic profile with a high statistical power of
      discrimination. This technique gives us the possibility to establish or exclude a
      match between a biological trace detected at a crime scene and a suspect whose
      DNA was collected via an oral swab. However, conventional techniques do tend to
      complexify the interpretation of complex DNA samples, such as degraded DNA and
      mixture DNA. The aim of this review is to highlight the powerness of new forensic
      DNA methods (including high-throughput sequencing or single-cell sequencing) to
      facilitate the interpretation of the expert with full compliance with existing
      french legislation.

PMID- 29200396
TI  - [Trained immunity in invertebrates: what do we know?]
AB  - One of the defense mechanisms of the host is the trained immunity, an immune
      component of the innate immunity, also known as innate immune memory. The trained
      immunity is defined as an exacerbated protection of an organism to a foreign
      body, such as a pathogenic microorganism, upon a second contact with it. This
      kind of immunity does not involve the components of acquired immunity, such as
      the B lymphocytes or T lymphocytes. It relies heavily on the cellular and
      molecular machinery of the innate response. Trained immunity is described as
      being present in both invertebrates and vertebrates, but its mechanisms have only
      recently begun to be elucidated, particularly in the vertebrates. Today, most of
      the research about innate immune memory deals with vertebrate models, forgetting
      that this mechanism exists in invertebrates. Investigating trained immunity in
      invertebrates gives the advantage to work with models naturally lacking acquired
      immunity. The aim of this review is to take stock of the knowledge concerning the
      trained immunity entailed in invertebrates.

PMID- 29200397
TI  - [Importance of intestinal paleomicrobiome study for contemporaneous medical
      problematics].
AB  - Human gut microbiome composition and diversity increasingly appear as a reliable
      marker of human evolution within his environment, and of health and its
      alteration (concept of dysbiosis); as a matter of fact, it can be considered as a
      strong marker of the disease status of individuals. Thus, in retrospect, the
      capacity to profile the gut microbiome would offer a great opportunity to
      identify individual and societal changes to which ancient populations were
      exposed. A global and diachronic view of the gut microbiome evolution is
      necessary in order to highlight the potential role of environmental factors or
      human habits in this process. However, to make the most of its contribution,
      archaeo-microbiology should aim at being as exhaustive as possible, encompassing
      parasites which have likely played a major role in the development of the
      mammalian immune system, and viruses.

PMID- 29200398
TI  - [Stressful work and heart do not get along well].
AB  - As other occupational risk factors, like noise, heat or some chemicals, stress at
      work may induce coronary heart disease. Occupational stress has several
      components and is usually measured using two different instruments: the Karasek
      model defines the job strain as the association between high constraints and low
      latitude at work, whereas the Siegrist model relies on the imbalance between
      efforts at work and rewards. It is now well established that occupational stress
      is an independent risk factor of coronary heart disease, the attributable risk
      fraction being about 3.5%, yielding some 3,400-4,000 incident cases each year in
      France. Several biological mechanisms have been hypothesized to explain how
      stress can induce coronary heart disease, but this remains largely unknown.

PMID- 29200399
TI  - [Why have we only two P53 genes?]
AB  - In this forum, we develop the idea that the human genome may not be equipped to
      protect us after the age of reproduction against certain diseases such as cancer
      or neuro-degenerative diseases. We take as example cancer and show that adding
      one tumor suppressor in the mouse genome in its genomic context (BAC transgene)
      provides some protection against spontaneous and induced tumors. We also show
      that in certain species displaying a resistance to cancer, there is an
      amplification of some tumor suppressor genes.

PMID- 29200400
TI  - [Should the knowledge be imperative? The key challenge of high throughput
      genetics].

PMID- 29200401
TI  - [CAR-T immunotherapy, a regulatory milestone].
AB  - The first therapy based on chimeric antigen receptors has been approved by the
      FDA. It gives excellent results in recurrent paediatric ALL; its cost is very
      high but fairly consistent with the clinical benefit (long term remission
      approaching a cure). In spite of their complexity and cost, CAR-T therapies will
      probably end up playing a very significant role in cancer therapy.

PMID- 29200402
TI  - Can a smartphone app improve medical trainees' knowledge of antibiotics?
AB  - Objectives: To determine whether a smartphone app, containing local bacterial
      resistance patterns (antibiogram) and treatment guidelines, improved knowledge of
      prescribing antimicrobials among medical trainees. Methods: We conducted a
      prospective, controlled, pre-post study of medical trainees with access to a
      smartphone app (app group) containing our hospital's antibiogram and treatment
      guidelines compared to those without access (control group). Participants
      completed a survey which included a knowledge assessment test (score range, 0
      [lowest possible score] to 12 [highest possible score]) at the start of the study
      and four weeks later. The primary outcome was change in mean knowledge assessment
      test scores between week 0 and week 4. Change in knowledge assessment test scores
      in the app group were compared to the difference in scores in the control group
      using multivariable linear regression. Results: Sixty-two residents and senior
      medical students participated in the study. In a multivariable analysis
      controlling for sex and prior knowledge, app use was associated with a 1.1 point
      (95% CI: 0.10, 2.1) [beta = 1.08, t(1) = 2.08, p = 0.04]  higher change in
      knowledge score compared to the change in knowledge scores in the control group.
      Among those in the app group, 88% found it easy to navigate, 85% found it useful,
      and about one- quarter used it daily. Conclusions: An antibiogram and treatment
      algorithm app increased knowledge of prescribing antimicrobials in the context of
      local antibiotic resistance patterns. These findings reinforce the notion that
      smartphone apps can be a useful and innovative means of delivering medical
      education.

PMID- 29200403
TI  - Disaster management and primary health care: implications for medical education.

PMID- 29200405
TI  - Posteromedial Corner Knee Injuries: Diagnosis, Management, and Outcomes: A
      Critical Analysis Review.

PMID- 29200404
TI  - STAT5BN642H is a driver mutation for T cell neoplasia.
AB  - STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B
      mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma
      patients. Here, we used the Vav1 promoter to generate transgenic mouse models
      that expressed either human STAT5B or STAT5BN642H in the hematopoietic
      compartment. While STAT5B-expressing mice lacked a hematopoietic phenotype, the
      STAT5BN642H-expressing mice rapidly developed T cell neoplasms. Neoplasia
      manifested as transplantable CD8+ lymphoma or leukemia, indicating that the
      STAT5BN642H mutation drives cancer development. Persistent and enhanced levels of
      STAT5BN642H tyrosine phosphorylation in transformed CD8+ T cells led to profound
      changes in gene expression that were accompanied by alterations in DNA
      methylation at potential histone methyltransferase EZH2-binding sites. Aurora
      kinase genes were enriched in STAT5BN642H-expressing CD8+ T cells, which were
      exquisitely sensitive to JAK and Aurora kinase inhibitors. Together, our data
      suggest that JAK and Aurora kinase inhibitors should be further explored as
      potential therapeutics for lymphoma and leukemia patients with the STAT5BN642H
      mutation who respond poorly to conventional chemotherapy.

PMID- 29200406
TI  - Sensorineural hearing loss in a patient with Swyer syndrome.

PMID- 29200407
TI  - A MECOM variant in an African American child with radioulnar synostosis and
      thrombocytopenia.

PMID- 29200409
TI  - Falls in Hospitalized Children With Neurodevelopmental Conditions: A Cross
      sectional, Correlational Study.
AB  - PURPOSE: The aim of the current study was to investigate in-hospital falls among
      children with neurological or neurodevelopmental conditions and investigated
      associated child characteristics. DESIGN: A cross-sectional, correlational study
      design was used in this study. A total of 446 patients were enrolled in the
      study, of which 298 were admitted with neurological conditions and 148 with
      neurodevelopmental conditions. METHODS: Intelligent quotient (IQ) was assessed
      according to age, and the Humpty Dumpty Falls Scale (HDFS) was completed and
      scored for each participant. FINDINGS: The neurodevelopmental group showed higher
      HDFS total mean score (p = .001) compared to the neurological group. We found
      that fall rates are more frequent (p = .003) in the neurodevelopmental group
      (12.9%) compared with the neurological group (5.1%). In addition, we found that,
      in both groups, HDFS total mean score correlates negatively with children's age,
      gender and IQ. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study
      suggest that the fall prevention programs must be implemented in children with
      neurodevelopmental conditions, not only in children with neurological conditions.

PMID- 29200408
TI  - Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an
      ACE gene polymorphism and myxomatous mitral valve disease.
AB  - OBJECTIVES: Myxomatous mitral valve disease (MMVD) is the most common heart
      disease in the dog. It is particularly common in the Cavalier King Charles
      Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin
      converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE
      gene polymorphism associated with a decrease in angiotensin-converting enzyme
      (ACE) activity. The aim of this study was to evaluate for the prevalence of the
      ACE polymorphism in CKCS with mitral valve disease and to determine whether the
      presence of the polymorphism is associated with alterations in ACE activity at
      different stages of cardiac disease. METHODS: Seventy-three dogs with a diagnosis
      of mitral valve disease were evaluated and a blood sample was drawn for ACE
      polymorphism genotyping and ACE activity measurement. RESULTS: Forty-three dogs
      were homozygous for the ACE polymorphism; five were heterozygous and 25 were
      homozygous wild type. The mean age and the median severity of disease were not
      different for dogs with the polymorphism and dogs with the wild-type sequence.
      The median baseline ACE activity was significantly lower for the ACE polymorphism
      (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more
      severe disease and the ACE polymorphism had significantly lower levels of ACE
      activity than dogs with the wild-type sequence (P=0.03). CONCLUSION: The CKCS
      appears to have a high prevalence of the ACE variant. Dogs with the ACE variant
      had lower levels of ACE activity even in more advanced mitral valve disease than
      dogs without the variant. The clinical significance of this finding and its
      impact on the need for ACE-I in dogs with the polymorphism and heart disease
      deserves further study.

PMID- 29200410
TI  - Are rehabilitation outcomes after severe anoxic brain injury different from
      severe traumatic brain injury? A matched case-control study.
AB  - Many reports have investigated rehabilitation outcomes after a traumatic brain
      injury (TBI); however, comparably less is known about whether they differ from
      outcomes of an anoxic brain injury (ABI). Thus, we aimed to compare the
      rehabilitation outcomes of patients with ABI with control patients who have TBI.
      Forty participants with ABI and 40 participants with TBI were included in this
      retrospective study. Participants with ABI were matched with participants with
      TBI who had similar clinical characteristics such as age, initial Functional
      Independence Measurement (FIM) score, and duration of coma. FIM and Functional
      Ambulation Classification (FAC) scores on rehabilitation admission and on
      rehabilitation discharge were recorded. The FIM score in the ABI group was 41.7+/
      28.5 on rehabilitation admission and increased to 57.1+/-31.4 on rehabilitation
      discharge. The FIM score in the TBI group was 40.8+/-24.0 on rehabilitation
      admission and increased to 65.9+/-35.3 on rehabilitation discharge. There was no
      statistically significant difference in the FIM scores on rehabilitation
      discharge between groups. Initial FAC was similar in both groups and there was no
      statistically significant difference in the FAC scores on rehabilitation
      discharge. The multiple linear regression analysis showed that intensive care
      unit length of stay had an inverse relationship with the FAC change. We did not
      find significant differences in the rehabilitation outcomes of participants with
      ABI compared with participants with TBI. Considering the lack of information in
      the literature on ABI rehabilitation, this study may be important to guide
      rehabilitation teams.

PMID- 29200414
TI  - Real-world use of scalp cooling to reduce chemotherapy-related hair loss.

PMID- 29200411
TI  - A Multicenter and Randomized Controlled Trial of Bicyclol in the Treatment of
      Statin-Induced Liver Injury.
AB  - BACKGROUND The aim of this study was to evaluate the efficacy and safety of
      bicyclol treatment in statin-induced liver injury. MATERIAL AND METHODS The study
      included 168 patients with liver injury caused by statins. Patients were
      randomized into two four-week treatment groups: bicyclol 25 mg three times daily
      or polyene phosphatidylcholine 456 mg three times daily as control. Serum
      biochemical indexes were compared before and after treatment. RESULTS Significant
      differences in alanine transaminase (ALT) levels among the three measurements
      before and after treatment in the two groups at different time points were
      observed (p<0.01). There was a significant difference (p<0.01) between two weeks
      and four weeks after treatment compared to the baseline period. There was a
      significant interaction (p=0.003) between the two groups and time factors. After
      two and four weeks of treatment, the ALT levels in the control group (68.20+/
      26.31, 50.71+/-27.13 respectively) were higher compared to the ALT in the
      bicyclol group (49.33+/-21.39, 30.36+/-17.41 respectively) (p<0.01). After four
      weeks of treatment, the normalization rates of bicyclol and polyene
      phosphatidylcholine groups were 74.68% and 46.15%, respectively. The efficacy of
      bicyclol was significantly better than that of polyene phosphatidylcholine
      (p<0.05). The incidence of adverse reactions in the bicyclol and polyene
      phosphatidylcholine groups were 2.53% and 2.56%, respectively, with no
      statistically significant differences observed between the two groups (p>0.05).
      CONCLUSIONS These findings suggest that trends of ALT changes in the two groups
      were different, and the improvement of ALT was more obvious in the bicyclol
      group. Bicyclol is considered to be safe and effective in the treatment of statin
      induced liver injury.

PMID- 29200415
TI  - Advances in the management of fungal infections.

PMID- 29200416
TI  - Patient-derived tumor xenograft models in drug development.

PMID- 29200417
TI  - New guidelines from the NCCN for polycythemia vera.

PMID- 29200418
TI  - Immunotherapy in ovarian cancer: where are we now, and where are we going?

PMID- 29200419
TI  - A mind map for managing minimal residual disease in acute myeloid leukemia.
AB  - Advances in detecting traces of leukemia that were previously unidentifiable have
      increasingly led to the incorporation of information about residual disease into
      clinical decision making for patients with leukemia in both the postinduction and
      consolidation settings. This review discusses current concepts related to minimal
      residual disease (MRD), which is defined as submicroscopic disease detected
      during morphologic complete remission. The focus is on acute myeloid leukemia
      (AML). Basic methods for detecting MRD include flow cytometry, reverse
      transcription-polymerase chain reaction, and mutation analysis. Several studies
      using these assays have demonstrated prognostic implications based on MRD
      positive vs MRD-negative status. As our understanding of the biological factors
      responsible for MRD in AML evolves, residual disease should be evaluated in the
      context of other prognostic markers. Current therapeutic options for managing MRD
      in AML are limited, and the clinical implications of a positive MRD test result
      can be significant. Regarding individual patients, an evidence-based approach
      must be applied while the institution- and assay-specific differences that
      currently exist are considered. Challenges associated with MRD assessment, such
      as the limited standardization of available assays and the paucity of effective
      agents to eradicate MRD, will need to be overcome before physicians who treat
      leukemia can use MRD as a tool for clinical management.

PMID- 29200421
TI  - Urban networks among Chinese cities along "the Belt and Road": A case of web
      search activity in cyberspace.
AB  - "The Belt and Road" initiative has been expected to facilitate interactions among
      numerous city centers. This initiative would generate a number of centers, both
      economic and political, which would facilitate greater interaction. To explore
      how information flows are merged and the specific opportunities that may be
      offered, Chinese cities along "the Belt and Road" are selected for a case study.
      Furthermore, urban networks in cyberspace have been characterized by their
      infrastructure orientation, which implies that there is a relative dearth of
      studies focusing on the investigation of urban hierarchies by capturing
      information flows between Chinese cities along "the Belt and Road". This paper
      employs Baidu, the main web search engine in China, to examine urban hierarchies.
      The results show that urban networks become more balanced, shifting from a
      polycentric to a homogenized pattern. Furthermore, cities in networks tend to
      have both a hierarchical system and a spatial concentration primarily in regions
      such as Beijing-Tianjin-Hebei, Yangtze River Delta and the Pearl River Delta
      region. Urban hierarchy based on web search activity does not follow the existing
      hierarchical system based on geospatial and economic development in all cases.
      Moreover, urban networks, under the framework of "the Belt and Road", show
      several significant corridors and more opportunities for more cities,
      particularly western cities. Furthermore, factors that may influence web search
      activity are explored. The results show that web search activity is significantly
      influenced by the economic gap, geographical proximity and administrative rank of
      the city.

PMID- 29200420
TI  - The effect of novel therapies in high-molecular-risk multiple myeloma.
AB  - Multiple myeloma is a heterogeneous disease with a prognosis that varies with
      patient factors, disease burden, tumor biology, and treatments. Certain molecular
      abnormalities confer a worse prognosis and thus are considered high-risk. These
      include t(4;14), del(17p), t(14;16), t(14;20), hypodiploidy, and
      gain(1q)/del(1p). In our previous review in 2013, we discussed the effect of
      available therapies on prognosis in these high-risk patients. Since then, seven
      phase 3 clinical trials in relapsed myeloma with 1 to 3 lines of therapy have
      been conducted, resulting in the approval of panobinostat, ixazomib, daratumumab,
      and elotuzumab, as well as additional data on carfilzomib. In our current review
      of these studies, all the novel therapies resulted in an improvement in
      progression-free survival for high-risk patients, but none of the trials provided
      clear statistical evidence that they overcame high-risk status. Moreover, there
      are several limitations in the currently available data. For example, the
      patient's Revised International Staging System score is generally not reported,
      and even when it is reported, it is usually at the time of initial diagnosis
      rather than at the time of study entry. Furthermore, the methodology used to
      determine risk suffers from technologic issues. Finally, the clonal and allele
      burden and concurrent molecular abnormalities can affect risk status and
      prognosis. To determine the optimal therapy for high-risk patients, future
      clinical trials should provide standardized risk assessments for all patients in
      addition to hazard ratios for Kaplan-Meier survival curves of high-risk patients
      vs those of standard-risk patients to determine if high-risk status has truly
      been overcome by a novel agent.

PMID- 29200422
TI  - Whole-system approaches to improving the health and wellbeing of healthcare
      workers: A systematic review.
AB  - BACKGROUND: Healthcare professionals throughout the developed world report higher
      levels of sickness absence, dissatisfaction, distress, and "burnout" at work than
      staff in other sectors. There is a growing call for the 'triple aim' of
      healthcare delivery (improving patient experience and outcomes and reducing
      costs; to include a fourth aim: improving healthcare staff experience of
      healthcare delivery. A systematic review commissioned by the United Kingdom's
      (UK) Department of Health reviewed a large number of international healthy
      workplace interventions and recommended five whole-system changes to improve
      healthcare staff health and wellbeing: identification and response to local need,
      engagement of staff at all levels, and the involvement, visible leadership from,
      and up-skilling of, management and board-level staff. OBJECTIVES: This systematic
      review aims to identify whole-system healthy workplace interventions in
      healthcare settings that incorporate (combinations of) these recommendations and
      determine whether they improve staff health and wellbeing. METHODS: A
      comprehensive and systematic search of medical, education, exercise science, and
      social science databases was undertaken. Studies were included if they reported
      the results of interventions that included all healthcare staff within a
      healthcare setting (e.g. whole hospital; whole unit, e.g. ward) in collective
      activities to improve physical or mental health or promote healthy behaviours.
      RESULTS: Eleven studies were identified which incorporated at least one of the
      whole-system recommendations. Interventions that incorporated recommendations to
      address local need and engage the whole workforce fell in to four broad types: 1)
      pre-determined (one-size-fits-all) and no choice of activities (two studies); or
      2) pre-determined and some choice of activities (one study); 3) A wide choice of
      a range of activities and some adaptation to local needs (five studies); or, 3) a
      participatory approach to creating programmes responsive and adaptive to local
      staff needs that have extensive choice of activities to participate in (three
      studies). Only five of the interventions included substantial involvement and
      engagement of leadership and efforts aimed at up-skilling the leadership of staff
      to support staff health and wellbeing. Incorporation of more of the
      recommendations did not appear to be related to effectiveness. The heterogeneity
      of study designs, populations and outcomes excluded a meta-analysis. All studies
      were deemed by their authors to be at least partly effective. Two studies
      reported statistically significant improvement in objectively measured physical
      health (BMI) and eight in subjective mental health. Six studies reported
      statistically significant positive changes in subjectively assessed health
      behaviours. CONCLUSIONS: This systematic review identified 11 studies which
      incorporate at least one of the Boorman recommendations and provides evidence
      that whole-system healthy workplace interventions can improve health and
      wellbeing and promote healthier behaviours in healthcare staff.

PMID- 29200423
TI  - Analysing increasing trends of Guillain-Barre Syndrome (GBS) and dengue cases in
      Hong Kong using meteorological data.
AB  - BACKGROUND: Guillain-Barre Syndrome (GBS) is a severe paralytic neuropathy
      associated with virus infections such as Zika virus and Chikungunya virus. There
      were also case reports of dengue fever preceding GBS. With the aim to understand
      the mechanisms of GBS and dengue outbreaks, this ecological study investigates
      the relationships between GBS, dengue, meteorological factors in Hong Kong and
      global climatic factors from January 2000 to June 2016. METHODS: The correlations
      between GBS, dengue, Multivariate El Nino Southern Oscillation Index (MEI) and
      local meteorological data were explored by Spearman's Rank correlations and cross
      correlations. Three Poisson regression models were fitted to identify non-linear
      associations among GBS, dengue and MEI. Cross wavelet analyses were applied to
      infer potential non-stationary oscillating associations among GBS, dengue and
      MEI. FINDINGS AND CONCLUSION: We report a substantial increasing of local GBS and
      dengue cases (mainly imported) in recent year in Hong Kong. The seasonalities of
      GBS and dengue are different, in particular, GBS is low while dengue is high in
      the summer. We found weak but significant correlations between GBS and local
      meteorological factors. MEI could explain over 17% of dengue's variations based
      on Poisson regression analyses. We report a possible non-stationary oscillating
      association between dengue fever and GBS cases in Hong Kong. This study has led
      to an improved understanding about the timing and ecological relationships
      between MEI, GBS and dengue.

PMID- 29200424
TI  - Arm rehabilitation in post stroke subjects: A randomized controlled trial on the
      efficacy of myoelectrically driven FES applied in a task-oriented approach.
AB  - PURPOSE: Motor recovery of persons after stroke may be enhanced by a novel
      approach where residual muscle activity is facilitated by patient-controlled
      electrical muscle activation. Myoelectric activity from hemiparetic muscles is
      then used for continuous control of functional electrical stimulation (MeCFES) of
      same or synergic muscles to promote restoration of movements during task-oriented
      therapy (TOT). Use of MeCFES during TOT may help to obtain a larger functional
      and neurological recovery than otherwise possible. STUDY DESIGN: Multicenter
      randomized controlled trial. METHODS: Eighty two acute and chronic stroke victims
      were recruited through the collaborating facilities and after signing an informed
      consent were randomized to receive either the experimental (MeCFES assisted TOT
      (M-TOT) or conventional rehabilitation care including TOT (C-TOT). Both groups
      received 45 minutes of rehabilitation over 25 sessions. Outcomes were Action
      Research Arm Test (ARAT), Upper Extremity Fugl-Meyer Assessment (FMA-UE) scores
      and Disability of the Arm Shoulder and Hand questionnaire. RESULTS: Sixty eight
      subjects completed the protocol (Mean age 66.2, range 36.5-88.7, onset months
      12.7, range 0.8-19.1) of which 45 were seen at follow up 5 weeks later. There
      were significant improvements in both groups on ARAT (median improvement: MeCFES
      TOT group 3.0; C-TOT group 2.0) and FMA-UE (median improvement: M-TOT 4.5; C-TOT
      3.5). Considering subacute subjects (time since stroke < 6 months), there was a
      trend for a larger proportion of improved patients in the M-TOT group following
      rehabilitation (57.9%) than in the C-TOT group (33.2%) (difference in proportion
      improved 24.7%; 95% CI -4.0; 48.6), though the study did not meet the planned
      sample size. CONCLUSION: This is the first large multicentre RCT to compare
      MeCFES assisted TOT with conventional care TOT for the upper extremity. No
      adverse events or negative outcomes were encountered, thus we conclude that
      MeCFES can be a safe adjunct to rehabilitation that could promote recovery of
      upper limb function in persons after stroke, particularly when applied in the
      subacute phase.

PMID- 29200425
TI  - Correction: A systematic review and meta-analysis of preclinical trials testing
      anti-toxin therapies for B. anthracis infection: A need for more robust study
      designs and results.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182879.].

PMID- 29200426
TI  - Characterization of dFOXO binding sites upstream of the Insulin Receptor P2
      promoter across the Drosophila phylogeny.
AB  - The insulin/TOR signal transduction pathway plays a critical role in determining
      such important traits as body and organ size, metabolic homeostasis and life
      span. Although this pathway is highly conserved across the animal kingdom, the
      affected traits can exhibit important differences even between closely related
      species. Evolutionary studies of regulatory regions require the reliable
      identification of transcription factor binding sites. Here we have focused on the
      Insulin Receptor (InR) expression from its P2 promoter in the Drosophila genus,
      which in D. melanogaster is up-regulated by hypophosphorylated Drosophila FOXO
      (dFOXO). We have finely characterized this transcription factor binding sites in
      vitro along the 1.3 kb region upstream of the InR P2 promoter in five Drosophila
      species. Moreover, we have tested the effect of mutations in the characterized
      dFOXO sites of D. melanogaster in transgenic flies. The number of experimentally
      established binding sites varies across the 1.3 kb region of any particular
      species, and their distribution also differs among species. In D. melanogaster,
      InR expression from P2 is differentially affected by dFOXO binding sites at the
      proximal and distal halves of the species 1.3 kb fragment. The observed uneven
      distribution of binding sites across this fragment might underlie their
      differential contribution to regulate InR transcription.

PMID- 29200427
TI  - A unique plasma microRNA profile defines type 2 diabetes progression.
AB  - A major unmet medical need to better manage Type 2 Diabetes (T2D) is the accurate
      disease prediction in subjects who show glucose dysmetabolism, but are not yet
      diagnosed as diabetic. We investigated the possibility to predict/monitor the
      progression to T2D in these subjects by retrospectively quantifying blood
      circulating microRNAs in plasma of subjects with i) normal glucose tolerance
      (NGT, n = 9); ii) impaired glucose tolerance (IGT, n = 9), divided into non
      progressors (NP, n = 5) and progressors (P, n = 4) based on subsequent diabetes
      occurrence, and iii) newly diagnosed T2D (n = 9). We found that impaired glucose
      tolerance associated with a global increase of plasma circulating microRNAs.
      While miR-148 and miR-222 were specifically modulated in diabetic subjects and
      correlated with parameters of glucose tolerance, the most accentuated microRNA
      dysregulation was found in NP IGT subjects, with increased level of miR-122, miR
      99 and decreased level of let-7d, miR-18a, miR-18b, miR-23a, miR-27a, miR-28 and
      miR-30d in comparison with either NGT or T2D. Interestingly, several of these
      microRNAs significantly correlated with parameters of cholesterol metabolism. In
      conclusion, we observed the major perturbation of plasma circulating microRNA in
      NP pre-diabetic subjects and identified a unique microRNA profile that may become
      helpful in predicting diabetic development.

PMID- 29200429
TI  - Correction: Role of the N-terminus for the stability of an amyloid-beta fibril
      with three-fold symmetry.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186347.].

PMID- 29200428
TI  - Low empathy-like behaviour in male mice associates with impaired sociability,
      emotional memory, physiological stress reactivity and variations in
      neurobiological regulations.
AB  - Deficits in empathy have been proposed to constitute a hallmark of several
      psychiatric disturbances like conduct disorder, antisocial and narcissistic
      personality disorders. Limited sensitivity to punishment, shallow or deficient
      affect and reduced physiological reactivity to environmental stressors have been
      often reported to co-occur with limited empathy and contribute to the onset of
      antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion) is
      addressed in preclinical models through the evaluation of the social transmission
      of emotional states: mice exposed to a painful stimulus display a higher response
      if in the presence of a familiar individual experiencing a higher degree of
      discomfort, than in isolation. In the present study, we investigated whether a
      reduction of emotional contagion can be considered a predictor of reduced
      sociality, sensitivity to punishment and physiological stress reactivity. To this
      aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then
      discretised their values in four quartiles. The upper (i.e. Emotional Contagion
      Prone, ECP) and the lower (i.e. Emotional Contagion Resistant, ECR) quartiles
      constituted the experimental groups. Our results indicate that mice in the lower
      quartile are characterized by reduced sociability, impaired memory of negative
      events and dampened hypothalamic-pituitary-adrenocortical reactivity to external
      stressors. Furthermore, in the absence of changes in oxytocin receptor density,
      we show that these mice exhibit elevated concentrations of oxytocin and
      vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain
      areas. Thus, not only do present results translate to the preclinical
      investigation of psychiatric disturbances, but also they can contribute to the
      study of emotional contagion in terms of its adaptive significance.

PMID- 29200430
TI  - Long-term sensorimotor adaptation in the ocular following system of primates.
AB  - The sudden movement of a wide-field image leads to a reflexive eye tracking
      response referred to as short-latency ocular following. If the image motion
      occurs soon after a saccade the initial speed of the ocular following is
      enhanced, a phenomenon known as post-saccadic enhancement. We show in macaque
      monkeys that repeated exposure to the same stimulus regime over a period of
      months leads to progressive increases in the initial speeds of ocular following.
      The improvement in tracking speed occurs for ocular following with and without a
      prior saccade. As a result of the improvement in ocular following speeds, the
      influence of post-saccadic enhancement wanes with increasing levels of training.
      The improvement in ocular following speed following repeated exposure to the same
      oculomotor task represents a novel form of sensori-motor learning in the context
      of a reflexive movement.

PMID- 29200431
TI  - Post-illumination cellular effects of photodynamic treatment.
AB  - Increased interest in clinical application of photodynamic therapy (PDT) in
      various medical fields poses a demand for better understanding of processes
      triggered by photo-treatment. Most of the work on PDT performed so far has
      focused on the immediate effects of photo-treatment. It is generally accepted
      that cellular damage occurs during light exposure and within a short period
      thereafter. If cells are not killed during the PDT, they might recover, depending
      on the extent of the photo-induced damage. Little is known, however, about the
      relationship between the properties of photosensitizers (PSs) and the delayed
      consequences of PDT. The aim of this work was to investigate cellular responses
      to sub-lethal photodynamic treatment and how toxicogenic potency may be affected
      by molecular features of the PS. Results demonstrated that for cationic porphyrin
      based PSs, lipophilicity is the main factor determining the fate of the cells in
      the 24-hour post-illumination period. PSs with amphiphilic properties initiated
      oxidative reactions that continued in the dark, long after light exposure, and
      caused suppression of metabolism and loss of cell viability with concomitant
      changes in electrophoretic mobility of proteins, including caspases. Apoptotic
      activity was not stimulated in the post-illumination period. This study
      demonstrated that in PDT mediated by amphiphilic cationic metalloporphyrin PSs,
      even when immediate photo-damage is relatively mild, destructive oxidative
      processes initiated during PDT continue in the absence of light to substantially
      impair metabolism, and that post-illumination protein modification may modify
      utilization of cell death pathways.

PMID- 29200432
TI  - Culturally appropriate organization of water and sewerage projects built through
      public private partnerships.
AB  - This paper contributes to the pursuit of socially sustainable water and
      sanitation infrastructure for all people by discovering statistically robust
      relationships between Hofstede's dimensions of cross-cultural comparison and the
      choice of contract award types, project type, and primary revenue sources. This
      analysis, which represents 973 projects distributed across 24 low- and middle
      income nations, uses a World Bank dataset describing high capital cost water and
      sewerage projects funded through private investment. The results show that
      cultural dimensions explain variation in the choice of contract award types,
      project type, and primary revenue sources. These results provide empirical
      evidence that strategies for water and sewerage project organization are not
      culturally neutral. The data show, for example, that highly individualistic
      contexts are more likely to select competitive contract award types and to depend
      on user fees to provide the primary project revenue stream post-construction. By
      selecting more locally appropriate ways to organize projects, project
      stakeholders will be better able to pursue the construction of socially
      sustainable water and sewerage infrastructure.

PMID- 29200433
TI  - Generation of Ca2+-independent sortase A mutants with enhanced activity for
      protein and cell surface labeling.
AB  - Sortase A, a calcium-dependent transpeptidase derived from Staphylococcus aureus,
      is used in a broad range of applications, such as the conjugation of fluorescent
      dyes and other moieties to proteins or to the surface of eukaryotic cells. In
      vivo and cell-based applications of sortase have been somewhat limited by the
      large range of calcium concentrations, as well as by the often transient nature
      of protein-protein interactions in living systems. In order to use sortase A for
      cell labeling applications, we generated a new sortase A variant by combining
      multiple mutations to yield an enzyme that was both calcium-independent and
      highly active. This variant has enhanced activity for both N- and C-terminal
      labeling, as well as for cell surface modification under physiological
      conditions.

PMID- 29200436
TI  - Genomic selection of crossing partners on basis of the expected mean and variance
      of their derived lines.
AB  - In a line or a hybrid breeding program superior lines are selected from a
      breeding pool as parental lines for the next breeding cycle. From a cross of two
      parental lines, new lines are derived by single-seed descent (SSD) or doubled
      haploid (DH) technology. However, not all possible crosses between the parental
      lines can be carried out due to limited resources. Our objectives were to present
      formulas to characterize a cross by the mean and variance of the genotypic values
      of the lines derived from the cross, and to apply the formulas to predict means
      and variances of flowering time traits in recombinant inbred line families of a
      publicly available data set in maize. We derived formulas which are based on the
      expected linkage disequilibrium (LD) between two loci and which can be used for
      arbitrary mating systems. Results were worked out for SSD and DH lines derived
      from a cross after an arbitrary number of intermating generations. The means and
      variances were highly correlated with results obtained by the simulation software
      PopVar. Compared with these simulations, computation time for our closed formulas
      was about ten times faster. The means and variances for flowering time traits
      observed in the recombinant inbred line families of the investigated data set
      showed correlations of around 0.9 for the means and of 0.46 and 0.65 for the
      standard deviations with the estimated values. We conclude that our results
      provide a framework that can be exploited to increase the efficiency of hybrid
      and line breeding programs by extending genomic selection approaches to the
      selection of crossing partners.

PMID- 29200435
TI  - A model of individualized canonical microcircuits supporting cognitive
      operations.
AB  - Major cognitive functions such as language, memory, and decision-making are
      thought to rely on distributed networks of a large number of basic elements,
      called canonical microcircuits. In this theoretical study we propose a novel
      canonical microcircuit model and find that it supports two basic computational
      operations: a gating mechanism and working memory. By means of bifurcation
      analysis we systematically investigate the dynamical behavior of the canonical
      microcircuit with respect to parameters that govern the local network balance,
      that is, the relationship between excitation and inhibition, and key intrinsic
      feedback architectures of canonical microcircuits. We relate the local behavior
      of the canonical microcircuit to cognitive processing and demonstrate how a
      network of interacting canonical microcircuits enables the establishment of
      spatiotemporal sequences in the context of syntax parsing during sentence
      comprehension. This study provides a framework for using individualized canonical
      microcircuits for the construction of biologically realistic networks supporting
      cognitive operations.

PMID- 29200434
TI  - Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and
      the effect of iron chelators.
AB  - Patients suffering from the progressive neurodegenerative disease Friedreich's
      ataxia have reduced expression levels of the protein frataxin. Three major
      isoforms of human frataxin have been identified, FXN42-210, FXN56-210 and FXN81
      210, of which FXN81-210 is considered to be the mature form. Both long forms,
      FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric
      particles stabilized by the extended N-terminal sequence. The short variant FXN81
      210, on other hand, has only been observed in the monomeric state. However, a
      highly homologous E. coli frataxin CyaY, which also lacks an N-terminal
      extension, has been shown to oligomerize in the presence of iron. To explore the
      mechanisms of stabilization of short variant frataxin oligomers we compare here
      the effect of iron on the oligomerization of CyaY and FXN81-210. Using dynamic
      light scattering, small-angle X-ray scattering, electron microscopy (EM) and
      cross linking mass spectrometry (MS), we show that at aerobic conditions in the
      presence of iron both FXN81-210 and CyaY form oligomers. However, while CyaY
      oligomers are stable over time, FXN81-210 oligomers are unstable and dissociate
      into monomers after about 24 h. EM and MS studies suggest that within the
      oligomers FXN81-210 and CyaY monomers are packed in a head-to-tail fashion in
      ring-shaped structures with potential iron-binding sites located at the interface
      between monomers. The higher stability of CyaY oligomers can be explained by a
      higher number of acidic residues at the interface between monomers, which may
      result in a more stable iron binding. We also show that CyaY oligomers may be
      dissociated by ferric iron chelators deferiprone and DFO, as well as by the
      ferrous iron chelator BIPY. Surprisingly, deferiprone and DFO stimulate FXN81-210
      oligomerization, while BIPY does not show any effect on oligomerization in this
      case. The results suggest that FXN81-210 oligomerization is primarily driven by
      ferric iron, while both ferric and ferrous iron participate in CyaY oligomer
      stabilization. Analysis of the amino acid sequences of bacterial and eukaryotic
      frataxins suggests that variations in the position of the acidic residues in
      helix 1, beta-strand 1 and the loop between them may control the mode of frataxin
      oligomerization.

PMID- 29200437
TI  - Food cleaning in gorillas: Social learning is a possibility but not a necessity.
AB  - Food cleaning is widespread in the animal kingdom, and a recent report confirmed
      that (amongst other behaviours) wild western lowland gorillas also show food
      cleaning. The authors of this report conclude that this behaviour, based on its
      distribution patterns, constitutes a potential candidate for culture. While
      different conceptualisations of culture exist, some more and some less reliant on
      behavioural form copying, all of them assign a special role to social learning
      processes in explaining potentially cultural behaviours. Here we report the
      results of an experiment that tested to what extent food cleaning behaviour in a
      group of captive Western lowland gorillas (Gorilla gorilla gorilla) relies on
      social learning processes. Subjects were provided with clean and dirty apples.
      When they were provided with dirty apples, all subjects showed evidence of food
      cleaning in at least 75% of trials. Preferred cleaning techniques differed
      between individuals, four out of five of subjects expressed a behaviour analogous
      to that reported in wild conspecifics. Given this occurrence of food cleaning in
      a culturally unconnected population of gorillas, we conclude that social learning
      is unlikely to play a central role in the emergence of the food cleaning
      behavioural form in Western lowland gorillas; instead, placing a greater emphasis
      on individual learning of food cleaning's behavioural form.

PMID- 29200438
TI  - Synthesis of Higher alpha-Chlorovinyl and alpha-Bromovinyl Amino Acids: The Amino
      Protecting Group Determines the Reaction Course.
AB  - N-Trifluoroacetyl alpha-vinyl amino esters are smoothly converted to the
      corresponding alpha-chlorovinyl or alpha-bromovinyl amino esters through the
      agency of phenyselenyl chloride or phenylselenyl bromide, respectively, followed
      by oxidation and pyrolysis. Exclusively the (E)-extemal halovinyl isomer and the
      internal halovinyl isomer are observed. The amino protecting group is a critical
      determinant of the reaction course (alkene addition vs. 5-exo-trig-like
      cyclization).

PMID- 29200439
TI  - Challenges to interpreting patient reported outcomes in clinical trials: author
      rejoinder.

PMID- 29200440
TI  - Erratum: Endoscopic ultrasound-guided gallbladder drainage for acute
      cholecystitis with a silicone-covered nitinol short bilaterally flared stent: a
      case series.
AB  - [This corrects the article DOI: 10.1055/s-0043-118659.].

PMID- 26401266
TI  - A Case Study of the Impediments to the Commercialization of Research at the
      University of Kentucky.
AB  - The commercialization of university-based research occurs to varying degrees
      between academic institutions. Previous studies have found that multiple barriers
      can impede the effectiveness and efficiency by which academic research is
      commercialized. This case study was designed to analyze the status of the
      commercialization activity at the University of Kentucky via a survey and
      interview with a successful academic entrepreneur in order to determine the
      impediments the individual perceived during the commercialization process. The
      study also garnered insight from the individual as to how the commercialization
      process could be improved. Issues with infrastructure were highlighted as the
      most significant barrier faced by the individual. The research subject also
      suggested that commercialization activity may generally increase if a number of
      factors were mitigated. Such insight can be communicated to the administrative
      leadership of the commercialization process at the University of Kentucky. Long
      term, improving university-based research commercialization will allow academic
      researchers to be more active and successful entrepreneurs such that intellectual
      property will progress more freely to the marketplace for the benefit of
      inventors, universities, and society.

PMID- 26535111
TI  - AGA: Interactive pipeline for reproducible genomics analyses.
AB  - Automated Genomics Analysis (AGA) is an interactive program to analyze high
      throughput genomic data sets on a variety of platforms. An easy to use, point and
      click, guided pipeline is implemented to combine, define, and compare datasets,
      and customize their outputs. In contrast to other automated programs, AGA enables
      flexible selection of sample groups for comparison from complex sample
      annotations. Batch correction techniques are also included to further enable the
      combination of datasets from diverse studies in this comparison. AGA also allows
      users to save plots, tables and data, and log files containing key portions of
      the R script run for reproducible analyses. The link between the interface and R
      supports collaborative research, enabling advanced R users to extend preliminary
      analyses generated from bioinformatics novices.

PMID- 26309725
TI  - Development of an image-based screening system for inhibitors of the plastidial
      MEP pathway and of protein geranylgeranylation.
AB  - We have recently established an in vivo visualization system for the
      geranylgeranylation of proteins in a stably transformed tobacco BY-2 cell line,
      which involves expressing a dexamethasone-inducible GFP fused to the prenylable,
      carboxy-terminal basic domain of the rice calmodulin CaM61, which naturally bears
      a CaaL geranylgeranylation motif (GFP-BD-CVIL). By using pathway-specific
      inhibitors it was demonstrated that inhibition of the methylerythritol phosphate
      (MEP) pathway with oxoclomazone and fosmidomycin, as well as inhibition of
      protein geranylgeranyl transferase type 1 (PGGT-1), shifted the localization of
      the GFP-BD-CVIL protein from the membrane to the nucleus. In contrast, the
      inhibition of the mevalonate (MVA) pathway with mevinolin did not affect this
      localization. Furthermore, complementation assays with pathway-specific
      intermediates confirmed that the precursors for the cytosolic isoprenylation of
      this fusion protein are predominantly provided by the MEP pathway. In order to
      optimize this visualization system from a more qualitative assay to a
      statistically trustable medium or a high-throughput screening system, we
      established new conditions that permit culture and analysis in 96-well microtiter
      plates, followed by fluorescence microscopy. For further refinement, the existing
      GFP-BD-CVIL cell line was transformed with an estradiol-inducible vector driving
      the expression of a RFP protein, C-terminally fused to a nuclear localization
      signal (NLS-RFP). We are thus able to quantify the total number of viable cells
      versus the number of inhibited cells after various treatments. This approach also
      includes a semi-automatic counting system, based on the freely available image
      processing software. As a result, the time of image analysis as well as the risk
      of user-generated bias is reduced to a minimum. Moreover, there is no cross
      induction of gene expression by dexamethasone and estradiol, which is an
      important prerequisite for this test system.

PMID- 25949808
TI  - Follow-up: Prospective compound design using the 'SAR Matrix' method and matrix
      derived conditional probabilities of activity.
AB  - In a previous Method Article, we have presented the 'Structure-Activity
      Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to
      systematically extract structurally related compound series from screening or
      chemical optimization data and organize these series and associated SAR
      information in matrices reminiscent of R-group tables. SARM calculations also
      yield many virtual candidate compounds that form a "chemical space envelope"
      around related series. To further extend the SARM approach, different methods are
      developed to predict the activity of virtual compounds. In this follow-up
      contribution, we describe an activity prediction method that derives conditional
      probabilities of activity from SARMs and report representative results of first
      prospective applications of this approach.

PMID- 29200445
TI  - Establishing the Validity and Reliability Evidence of Preceptor Assessment of
      Student Tool.
AB  - Objective. To evaluate the validity and reliability evidence of the preceptor
      assessment of student tool (PAST) which was designed to assess doctor of pharmacy
      (PharmD) student rotation performance. Methods. Evaluation data were loaded into
      WINSTEPS software to conduct a Rasch rating scale analysis. Validity evidence was
      examined from construct and content validity perspectives, and reliability was
      assessed via student and item separation index and reliability coefficient. Data
      from 435 observations were included in the analysis. Results. All 19 items
      measured the same construct of interest and the five-point rating scale
      functioned appropriately and differentiated students' ability. However, the
      item/person map indicated an absence of items at the end of the measurement
      continuum. Conclusion. Although adding items at the end of the measurement
      continuum may be beneficial, PAST showed good validity and reliability evidence
      when used to evaluate PharmD student rotations and is suitable to assess mastery
      learning.

PMID- 29200448
TI  - Clinical Track Program Expansion Increases Rotation Capacity for Experiential
      Program.
AB  - Objective. To evaluate the rotation capacity at the University of Maryland School
      of Pharmacy and see if the implementation of clinical track programs across the
      state correlates to an increase in rotation capacity for the school. Methods. The
      following information was collected: number of preceptors over the years in the
      school's experiential learning program, number of clinical track programs from
      2012 to 2015, rotation type, availability submissions per rotation type per year,
      and availability submissions per hospital participant in the clinical track
      program per year. The rotation capacity and rotation types from 2012 to 2015
      academic years were assessed and compared to see if there was any impact on the
      clinical track programs implemented. Results. There was no statistically
      significant difference in the frequency distribution of rotation types among all
      sites from 2012 through 2015 academic years. However, there was a statistically
      significant difference in the total number/capacity of rotations from 2012 to
      2015 academic years. There were also statistically significant differences in the
      rotation capacity in all sites except for three sites. Conclusion. Adding
      clinical track programs can help increase the capacity of a school's clinical
      rotations.

PMID- 29200446
TI  - Insights From the Defining Issues Test on Moral Reasoning Competencies
      Development in Community Pharmacists.
AB  - Objective. To investigate whether a profession-specific educational intervention
      affected the development of moral reasoning competencies in community
      pharmacists, as measured by the Defining Issues Test (DIT2). Methods. This
      research used a repeated measures pre-post educational intervention design as a
      quasi-randomized, controlled, crossover study to evaluate changes in the moral
      reasoning scores of 27 volunteer community pharmacists in Ireland. Results.
      Changes in pharmacists' moral reasoning competencies development, as reported by
      P-Scores and N2-Scores, were found to be significant. In addition, interaction
      effects were observed between developmental scores on the DIT2 and whether
      participants were determined to be consolidated in their reasoning pre- and post
      engagement with the educational intervention. Conclusion. Short profession
      specific educational interventions have the potential to positively affect the
      development of moral reasoning competencies of community pharmacists.

PMID- 29200447
TI  - Design and Validation of Patient-Centered Communication Tools (PaCT) to Measure
      Students' Communication Skills.
AB  - Objective. To develop a comprehensive instrument specific to student pharmacist
      patient communication skills, and to determine face, content, construct,
      concurrent, and predictive validity and reliability of the instrument. Methods. A
      multi-step approach was used to create and validate an instrument, including the
      use of external experts for face and content validity, students for construct
      validity, comparisons to other rubrics for concurrent validity, comparisons to
      other coursework for predictive validity, and extensive reliability and inter
      rater reliability testing with trained faculty assessors. Results. Patient
      centered Communication Tools (PaCT) achieved face and content validity and
      performed well with multiple correlation tests with significant findings for
      reliability testing and when compared to an alternate rubric. Conclusion. PaCT is
      a useful instrument for assessing student pharmacist communication skills with
      patients.

PMID- 29200449
TI  - Pharmacognosy, a Classical Theme Tuned to a Contemporary Melody.
AB  - Objective. To describe the development of a pharmacognosy course that uses a
      combination of didactic teaching, team-based projects, and practicum laboratory
      practice. Methods. A course titled "Pharmacognosy" was developed by applying a
      three-tier teaching methodology: in the classroom, the basic concepts and
      principles were introduced in a didactic manner; outside the classroom, students
      worked in teams and each team created an independent literature-based research
      project that was submitted as a poster presentation; in the pharmacy practicum
      laboratory, students worked individually and conducted a quality control
      experiment comprised of a quantitative analysis of an herbal product. Results.
      During the seven-year course implementation, 1091 first-year PharmD students
      participated in the course. Their performance was consistently satisfactory. On
      average, 30% of students in each class received a grade of "A" and teams received
      a "B" and above on their projects. Conclusion. The pharmacognosy course, equipped
      with concurrent teaching methods, implemented with a group research project, and
      reinforced by practicum laboratory experience, has reached the original goal of
      introducing a classical topic in an updated and contemporary fashion to meet the
      requirement of integrated pharmacy education and practice.

PMID- 29200450
TI  - An Analysis of California Pharmacy and Medical Students' Dietary and Lifestyle
      Practices.
AB  - Objective. To assess dietary and lifestyle practices of pharmacy and medical
      students in California and investigate whether they adhered to behaviors
      consistent with current dietary and exercise guidelines. Methods. The Block Brief
      2000 Food Frequency Questionnaire and a supplemental survey assessing
      demographics, exercise, and dietary behaviors were administered to students
      across 10 California pharmacy and medical schools. Results. While the majority of
      students consumed sodium <2300 mg/day (73%) and dietary cholesterol <300 mg/day
      (84%), only 50% had a saturated fat intake <=10% total kcal, 13% met fiber intake
      goals, 10% consumed >=8 servings/day of fruit and vegetables, and 41% exercised
      >=150 minutes/week. The largest barrier to consuming a healthful diet was lack of
      time. Conclusion. A high proportion of pharmacy and medical students in
      California did not meet many of the dietary and physical activity
      recommendations. Health care programs may benefit from implementing nutrition and
      lifestyle education in their curriculum.

PMID- 29200451
TI  - Incidence of Self-Reported Depression Among Pharmacy Residents in Tennessee.
AB  - Objective. To assess the incidence of self-reported depression among pharmacy
      residents in Tennessee. Methods. A 50-question survey was distributed to pharmacy
      residency program directors across Tennessee. Using questions modified from the
      Major Depression Inventory scale, subjects were asked to identify personal signs
      or symptoms of depression. The researcher observed trends of depression and
      offered mental health education to participating programs. Results. Eighty-four
      residents were potentially exposed to the survey with 50 participants, yielding a
      59% response rate. Of the 50 residents, 19 self-reported feeling depressed during
      residency. More concerning, 11 residents reported having suicidal thoughts.
      Additionally, 13 residents voiced they would benefit from mental health
      resources. Conclusion. Self-reported depression among pharmacy residents is not
      uncommon. Defining mental health benefit resources at the beginning of residency
      would be beneficial.

PMID- 29200452
TI  - Predisposition for Empathy, Intercultural Sensitivity, and Intentions for Using
      Motivational Interviewing in First Year Pharmacy Students.
AB  - Objective. To assess first-year pharmacy (P1) students' predispositions (eg,
      perceptions for empathy, intercultural sensitivity, and motivational interviewing
      (MI) as a patient-centered communication skillset) and identify potential
      curricula content/communication skills training needs. Methods. A cross-sectional
      survey was used to collect students' self-reported perceptions for empathy,
      intercultural sensitivity, counseling contexts, and projected future MI use.
      Relationships between variables were explored and logistic regression was used to
      evaluate intention for using MI in future patient encounters. Results. There were
      134 students who participated. Higher predisposition for empathy and for
      intercultural sensitivity were significantly correlated. Significant predictors
      for applying MI in future patient encounters were sex, confidence with counseling
      skills, and current use of MI. Conclusion. Results suggest the need to
      incorporate innovative training strategies in communication skills curricula.
      Potential areas include empathy, intercultural sensitivity and significant
      predictor variables for future MI use. Further investigation in other schools is
      needed.

PMID- 29200453
TI  - Targeting Assessment for Learning within Pharmacy Education.
AB  - Formative assessment is critical for deliberate improvement, development and
      growth. While not entirely synonymous, assessment for learning (AFL) is an
      approach using formative assessment to specifically improve students' learning.
      While using formative assessments, AFL can also have summative programmatic
      assessment implications. For each learning assessment, summative and formative
      uses can be leveraged; it can scaffold (formative), foster students' growth
      (formative), and document students' development in a competency/standard
      (summative). For example, using a developmental portfolio with iterative
      reflective-writings (formative), PharmD students showed qualitative development
      in the "professionalism" competency (summative; ACPE Standard 4.4). (In parallel,
      this development in professionalism was confirmed quantitatively.) An AFL
      approach can complement other assessments; it can be integrated with other
      summative assessments into a multi-method assessment program, wherein
      developmental portfolio sections could be used for a few specific competencies.
      While AFL is not a one-size-fits-all silver bullet approach for programmatic
      assessment, it is one notable robust tool to employ.

PMID- 29200454
TI  - Misuses of Regression and ANCOVA in Educational Research.

PMID- 29200455
TI  - Leadership Strengths and the Future of Pharmacy.

PMID- 29200456
TI  - Carpe Diem! Seizing the Rise of Co-Curricular Experiences.

PMID- 29200457
TI  - Another American Pharmacists Month Comes to a Close.

PMID- 29200458
TI  - The Report of the 2016-2017 Advocacy Standing Committee.
AB  - Based on the growing importance of community engagement and the recognition of
      its importance by the American Association of Colleges of Pharmacy (AACP), the
      committee offers several examples of community engagement activities for
      consideration and replication by our academy and beyond. These activities,
      including those of winning institutions of the Lawrence J. Weaver
      Transformational Community Engagement Award, can be mapped to the core components
      of community engagement presented in Table 1. The committee, using an
      implementation readiness framework, provides the reader with insight into the
      challenges that may impact successful community engagement and encourages our
      academy to continue its work to support faculty capacity in this area. Toward
      that end, the committee offers a policy statement that encourages schools and
      colleges of pharmacy to have an office or designate a faculty member whose focus
      is specifically on community engagement. The committee also offers a
      recommendation that the core components be included in the criteria for the
      Weaver Award.

PMID- 29200459
TI  - Competency, Programming, and Emerging Innovation in Graduate Education within
      Schools of Pharmacy: The Report of the 2016-2017 Research and Graduate Affairs
      Committee.
AB  - Graduate education in the pharmaceutical sciences is a cornerstone of research
      within pharmacy schools. Pharmaceutical scientists are critical contributors to
      addressing the challenges of new drug discovery, delivery, and optimal care in
      order to ensure improved therapeutic outcomes in populations of patients. The
      American Association of Colleges of Pharmacy (AACP) charged the 2016-2017
      Research and Graduate Affairs Committee (RGAC) to define the competencies
      necessary for graduate education in the pharmaceutical sciences (Charge 1),
      recommend collaborative curricular development across schools of pharmacy (Charge
      2), recommend AACP programing for graduate education (Charge 3), and provide
      guidance on emerging areas for innovation in graduate education (Charge 4). With
      respect to Charges 1 and 2, the RGAC committee developed six domains of core
      competencies for graduate education in the pharmaceutical sciences as well as
      recommendations for shared programming. For Charge 3, the committee made 3
      specific programming recommendations that include AACP sponsored regional
      research symposia, a professional development forum at the AACP INterim Meeting,
      and the addition of a graduate research and education poster session at the AACP
      Annual Meeting. For Charge 4, the committee recommended that AACP develop a
      standing committee of graduate program deans and directors to provide guidance to
      member schools in support of graduate program representation at AACP meetings,
      develop skills for interprofessional teamwork and augment research through
      integration of Pharm.D., Ph.D., postdoctoral associates, resident, and fellow
      experiences. Two proposed policy statements by the committee are that AACP
      believes core competencies are essential components of graduate education and
      AACP supports the inclusion of research and graduate education focuses in its
      portfolio of meetings and programs.

PMID- 29200460
TI  - Report of the 2016-2017 Student Affairs Standing Committee.
AB  - The 2016-2017 AACP Student Affairs Standing Committee addressed charges related
      to recruitment to the profession of pharmacy and a national awareness campaign
      for pharmacy careers, as well as promotion of student wellness and stress
      management. The Committee report provides six recommendations to the American
      Association of Colleges of Pharmacy (AACP) and one proposed policy statement for
      the AACP House of Delegates related to recruitment to the pharmacy profession.
      The Committee report also provides three recommendations to AACP and one proposed
      policy statement for the AACP House of Delegates related to student wellness and
      stress management. In addition, this report provides recommendations for future
      AACP Student Affairs Standing Committee work.

PMID- 29200462
TI  - Final Report of the 2016-17 Bylaws and Policy Development Committee: (Reflecting
      actions taken by the HOD on July 19, 2017).

PMID- 29200461
TI  - AACP Special Taskforce White Paper on Diversifying Our Investment in Human
      Capital.
AB  - The 2015-2017 American Association of Colleges of Pharmacy (AACP) Special
      Taskforce on Diversifying our Investment in Human Capital was appointed for a two
      year term, due to the rigors and complexities of its charges. This report serves
      as a white paper for academic pharmacy on diversifying our investment in human
      capital. The Taskforce developed and recommended a representation statement that
      was adapted and adopted by the AACP House of Delegates at the 2016 AACP Annual
      Meeting. In addition, the Taskforce developed a diversity statement for the
      Association that was adopted by the AACP Board of Directors in 2017. The
      Taskforce also provides recommendations to AACP and to academic pharmacy in this
      white paper.

PMID- 29200463
TI  - Aligning the AACP Strategic Engagement Agenda with Key Federal Priorities in
      Health: Report of the 2016-17 Argus Commission.
AB  - The Argus Commission identified three major federal priorities related to health
      care, including the precision medicine initiative, the Cancer Moonshot and the
      opioid abuse epidemic. Current activities at the federal level were summarized
      and an analysis of activities within the profession, and academic pharmacy
      specifically, was prepared. The implications for pharmacy education, research and
      practice are compelling in all three areas. Recommendations, suggestions and two
      policy statements aim to optimize the attention to these priorities by the
      academy. Further, aligning the AACP Strategic Engagement agenda with the
      opportunities and threats acknowledged in the analysis is essential.

PMID- 29200464
TI  - Grand Advantage: Family Wealth and Grandchildren's Educational Achievement in
      Sweden.
AB  - We study the role of family wealth for children's educational achievement using
      novel and unique Swedish register data. In particular, we focus on the
      relationship between grandparents' wealth and their grandchildren's educational
      achievement. Doing so allows us to reliably establish the independent role of
      wealth in contributing to long-term inequalities in opportunity. We use
      regression models with rich controls to account for observed socioeconomic
      characteristics of families, cousin fixed effects to net out potentially
      unobserved grandparental effects, and marginal structural models to account for
      endogenous selection. We find substantial associations between grandparents'
      wealth and their grandchildren's grade point averages (GPA) in the 9th grade that
      are only partly mediated by the socioeconomic characteristics and wealth of
      parents. Our findings indicate that family wealth inequality - even in a
      comparatively egalitarian context like Sweden - has profound consequences for the
      distribution of opportunity across multiple generations. We posit that our
      estimates of the long-term consequences of wealth inequality may be conservative
      for nations other than Sweden, like the United States, where family wealth - in
      addition to its insurance and normative functions - allows the direct purchase of
      educational quality and access.

PMID- 29200465
TI  - Lack of conformity to new local dietary preferences in migrating captive
      chimpanzees.
AB  - Conformity to the behavioural preferences of others can have powerful effects on
      intragroup behavioural homogeneity in humans, but evidence in animals remains
      minimal. In this study, we took advantage of circumstances in which individuals
      or pairs of captive chimpanzees, Pan troglodytes, were 'migrated' between groups,
      to investigate whether immigrants would conform to a new dietary population
      preference experienced in the group they entered, an effect suggested by recent
      fieldwork. Such 'migratory-minority' chimpanzees were trained to avoid one of two
      differently coloured foods made unpalatable, before 'migrating' to, and then
      observing, a 'local-majority' group consume a different food colour. Both
      migratory-minority and local-majority chimpanzees displayed social learning,
      spending significantly more time consuming the previously unpalatable, but
      instead now edible, food, than did control chimpanzees who did not see immigrants
      eat this food, nor emigrate themselves. However, following the migration of
      migratory-minority chimpanzees, these control individuals and the local-majority
      chimpanzees tended to rely primarily upon personal information, consuming first
      the food they had earlier learned was palatable before sampling the alternative.
      Thus, chimpanzees did not engage in conformity in the context we tested; instead
      seeing others eat a previously unpalatable food led to socially learned and
      adaptive re-exploration of this now-safe option in both minority and majority
      participants.

PMID- 29200466
TI  - Quantifying the expected value of uncertain management choices for over-abundant
      Greylag Geese.
AB  - In many parts of the world, conservation successes or global anthropogenic
      changes have led to increasing native species populations that then compete with
      human resource use. In the Orkney Islands, Scotland, a 60-fold increase in
      Greylag Goose Anser anser numbers over 24 years has led to agricultural damages
      and culling attempts that have failed to prevent population increase. To address
      uncertainty about why populations have increased, we combined empirical modelling
      of possible drivers of Greylag Goose population change with expert-elicited
      benefits of alternative management actions to identify whether to learn versus
      act immediately to reduce damages by geese. We built linear mixed-effects models
      relating annual goose densities on farms to land-use and environmental covariates
      and estimated AICc model weights to indicate relative support for six hypotheses
      of change. We elicited from experts the expected likelihood that one of six
      actions would achieve an objective of halting goose population growth, given each
      hypothesis for population change. Model weights and expected effects of actions
      were combined in Value of Information analysis (VoI) to quantify the utility of
      resolving uncertainty in each hypothesis through adaptive management and
      monitoring. The action with the highest expected value under existing uncertainty
      was to increase the extent of low quality habitats, whereas assuming equal
      hypothesis weights changed the best action to culling. VoI analysis showed that
      the value of learning to resolve uncertainty in any individual hypothesis for
      goose population change was low, due to high support for a single hypothesis of
      change. Our study demonstrates a two-step framework that learns about the most
      likely drivers of change for an over-abundant species, and uses this knowledge to
      weight the utility of alternative management actions. Our approach helps inform
      which strategies might best be implemented to resolve uncertainty when there are
      competing hypotheses for change and competing management choices.

PMID- 29200468
TI  - Holistic Admissions in the Health Professions: Strategies for Leaders.

PMID- 29200469
TI  - International Trends in Technological Progress: Evidence from Patent Citations,
      1980-2011.
AB  - We analyse cross-country trends in several aspects of technological progress
      during 1980-2011 by examining the US patent citations data. Our estimation
      results on patent quality and citation lags relative to the US reveal the
      following. The emerging Asian economies of Korea, Taiwan and China have achieved
      substantial catch-up. In the case of Korea and Taiwan, progress has been made in
      both patent quality and citation lags. China has achieved improvement in patent
      quality but not in citation lag. In contrast, advanced economies of Europe and
      Japan have displayed steady decline in patent quality, while the US has
      strengthened its position.

PMID- 29200467
TI  - Examination of the validity and reliability of the French version of the Brief
      Self-Control Scale.
AB  - This study aims to develop and to validate a French version of the Brief Self
      Control Scale (BSCS; Tangney et al., 2004). This instrument is usually applied as
      a unidimensional self-report measure for assessing trait self-control, which
      captures one's dispositional ability to resist short-term temptation in order to
      reach more valuable long-term goals. Data were collected from two independent
      samples of French-speaking individuals (n1 = 287; n2 = 160). Results indicated
      that the French version of the BSCS can be treated as unidimensional, like the
      original questionnaire. Data also showed consistent acceptable reliability and
      reasonable test-retest stability. Acceptable external validity of constructs was
      supported by relationships with self-reported measures of impulsivity (UPPS),
      including urgency, lack of premeditation, and lack of perseverance. Overall, the
      findings suggest that the average score of the French version of the BSCS is a
      viable option for assessing trait self-control in French speaking populations.

PMID- 29200470
TI  - Market versus Residence Principle: Experimental Evidence on the Effects of a
      Financial Transaction Tax.
AB  - The effects of a financial transaction tax (FTT) are scientifically disputed, as
      seemingly small details of its implementation may matter a lot. In this article,
      we provide experimental evidence on the different effects of an FTT, depending on
      whether it is implemented as a tax on markets, on residents, or a combination of
      both. We find that a tax on markets has negative effects on volatility and
      trading volume, whereas a tax on residents shows none of these undesired effects.
      Additionally, we observe that individual risk attitude is not related to traders'
      reaction to the different forms of an FTT.

PMID- 29200472
TI  - Surveillance or Self-Surveillance? Behavioral Cues Can Increase the Rate of
      Drivers' Pro-Environmental Behavior at a Long Wait Stop.
AB  - By leaving their engines idling for long periods, drivers contribute
      unnecessarily to air pollution, waste fuel, and produce noise and fumes that harm
      the environment. Railway level crossings are sites where many cars idle, many
      times a day. In this research, testing two psychological theories of influence,
      we examine the potential to encourage drivers to switch off their ignition while
      waiting at rail crossings. Two field studies presented different signs at a busy
      rail crossing site with a 2-min average wait. Inducing public self-focus (via a
      "Watching Eyes" stimulus) was not effective, even when accompanied by a written
      behavioral instruction. Instead, cueing a private-self focus ("think of
      yourself") was more effective, doubling the level of behavioral compliance. These
      findings confirm the need to engage the self when trying to instigate self
      regulatory action, but that cues evoking self-surveillance may sometimes be more
      effective than cues that imply external surveillance.

PMID- 29200471
TI  - Implementing the sterile insect technique with RNA interference - a review.
AB  - We review RNA interference (RNAi) of insect pests and its potential for
      implementing sterile insect technique (SIT)-related control. The molecular
      mechanisms that support RNAi in pest species are reviewed in detail, drawing on
      literature from a range of species including Drosophila melanogaster Meigen and
      Homo sapiens L. The underlying genes that enable RNAi are generally conserved
      across taxa, although variance exists in both their form and function. RNAi
      represents a plausible, non-GM system for targeting populations of insects for
      control purposes, if RNAi effector molecules can be delivered environmentally
      (eRNAi). We consider studies of eRNAi from across several insect orders and
      review to what extent taxonomy, genetics, and differing methods of double
      stranded (ds) RNA synthesis and delivery can influence the efficiency of gene
      knockdown. Several factors, including the secondary structure of the target mRNA
      and the specific nucleotide sequence of dsRNA effector molecules, can affect the
      potency of eRNAi. However, taxonomic relationships between insects cannot be used
      to reliably forecast the efficiency of an eRNAi response. The mechanisms by which
      insects acquire dsRNA from their environment require further research, but the
      evidence to date suggests that endocytosis and transport channels both play key
      roles. Delivery of RNA molecules packaged in intermediary carriers such as
      bacteria or nanoparticles may facilitate their entry into and through the gut,
      and enable the evasion of host defence systems, such as toxic pH, that would
      otherwise attenuate the potential for RNAi.

PMID- 29200473
TI  - Effect of Premature Rupture of Membranes on Induction of Labor: A Historical
      Cohort Study.
AB  - Objective: The aim of this study was to assess the influence of premature rupture
      of membranes (PROM) on the induction of labor. Material and Method: This
      historical cohort study analyzed 1861 inductions of labor at term using
      misoprostol which occurred between 2010 and 2015. Exclusion criteria included
      intrauterine fetal death, previous cesarean section, and fetal structural or
      chromosomal anomalies. Induction of labor for PROM (PROM group) was compared to
      induction for other indications (no-PROM group); the primary outcome measure was
      the cesarean section rate. Results: The cesarean section rate for the PROM group
      was significantly lower (21.9% vs. 26.3%, p = 0.029). The induction-to-delivery
      interval was shorter (mean: 972 [854 - 6734] min vs. 1741 [97 - 10 834] min, p <
      0.0001) and the rates of vaginal birth within 24 hours (80.9 vs. 52.0%, p =
      0.0001) and 48 hours (98.4 vs. 85.3%, p = 0.0001) were higher in the PROM group.
      The impact of PROM on the cesarean section rate was not significant in
      multivariate analysis; however, PROM was found to have the greatest effect on the
      induction-to-delivery interval (p < 0.0001). Conclusion: Premature rupture of
      membranes significantly affects various outcome measures when delivery is
      induced, particularly the induction-to-delivery interval.

PMID- 29200474
TI  - Personal Preference of Mode of Delivery. What do Urogynaecologists choose?
      Preliminary Results of the DECISION Study.
AB  - Introduction: Currently, almost every third child in Germany is delivered by
      caesarean section. Apart from straightforward and clear indications for caesarean
      section which account for approx. 10%, the large proportion of relative
      indications in particular needs to be critically reviewed if the current C
      section rate is to be effectively lowered. It is more than doubtful, however,
      whether this can be a realistic goal in Germany, especially in the context of
      international developments. All studies on this topic demonstrate that the
      personal attitude of the obstetric team has a considerable influence on the
      pregnant woman's personally preferred mode of delivery. Therefore, in the first
      part of the DECISION study, the personal preferences of urogynaecologists were
      evaluated regarding the best suitable mode of delivery. Material and Methods: All
      432 delegates at the 9th German Urogynaecology Congress in Stuttgart in April
      2017 were invited to participate in an online questionnaire study. The
      questionnaire was developed especially for this study. Results: Of the 432
      registered delegates, 189 (43.8%) participated in the survey. 84.7% (n = 160) of
      the study participants would prefer a vaginal delivery, in an otherwise
      uncomplicated pregnancy. Only 12.2% (n = 23) opted for an elective caesarean
      section. The main reasons stated for this decision were concerns about
      incontinence (87.5%) and pelvic floor trauma (79.2%). Amongst the study
      participants, 83.6% would like to be part of a risk stratification system
      presented in the questionnaire which, with the aid of specific parameters, is
      intended to allow early identification of a population with a high risk of
      developing pelvic floor disorders. There was also great interest in postpartum
      pelvic floor recovery (97.8%) and an associated optional pessary therapy (64.4%).
      The type of delivery already experienced (vaginal delivery vs. primary caesarean
      section) and parity also reveals to have a significant influence on the personal
      preferred mode of delivery as well. Conclusions: Urogynaecologists prefer vaginal
      delivery for themselves. There is a great interest to participate in a risk
      stratification process in order to approach childbirth in an individualized and
      risk-adapted manner.

PMID- 29200475
TI  - Pregnancy Outcomes in Maternal Neuropsychiatric Illness and Substance Abuse.
AB  - Introduction: Worldwide the prevalence of neuropsychiatric illness among women of
      reproductive age is higher than ever before. This study investigates the
      influences of maternal substance abuse/dependence and neuropsychiatric illness on
      pregnancy and neonatal outcomes. Patients and Methods: Using a retrospective
      study design 185 pregnancies in women with neuropsychiatric illnesses or
      substance abuse were identified at a single centre over a period of 3.25 years
      and compared to 4907 pregnancies in healthy women without mental illness.
      Differences in pre-, peri- and postnatal pregnancy parameters were studied.
      Results: Numbers of previous abortions on obstetric history were significantly
      higher in cases compared to controls, women with depression being especially
      affected. The number of antenatal visits was also higher among cases, especially
      in women with depression. The caesarean section rate was significantly higher in
      cases compared to controls. Children of women with neuropsychiatric illness were
      born at lower gestational ages than those of healthy control mothers, however
      there were no significant differences between case and control groups for birth
      weight, head circumference or Apgar scores. Some isolated differences were found
      for disease-specific case subgroups compared to controls. Conclusion: The study
      shows a relationship between maternal neuropsychiatric illness and pregnancy
      outcomes independent of medication use. Rates of spontaneous abortion were
      higher. Children were born earlier, yet the neonatal outcomes birth weight, head
      circumference and Apgar score were not worse than children of mentally healthy
      women.

PMID- 29200476
TI  - Outcome of Cesarean Myomectomy: Is it a Safe Procedure?
AB  - Objective: Myomectomy performed during cesarean section is still controversial
      because of the potential for associated complications, especially with large
      myomas. Many obstetricians avoid performing cesarean myomectomy procedures
      because of the risk of uncontrollable hemorrhage. However, the prevalence of
      pregnant women with myomas is increasing, leading to an increase in the
      likelihood that physicians will encounter this issue. The aim of this study was
      to compare outcomes and complications of patients who either had or did not have
      cesarean myomectomy. Method: A total of 361 patients were evaluated in this
      retrospective study. Patients who had cesarean section with myomectomy and
      patients had cesarean section without myomectomy were compared with regard to
      demographics, drop in hemoglobin levels, complications, blood transfusion rates
      and duration of operation. These parameters were also compared when the diameter
      of the myoma was larger than 5 cm. Values of p < 0.01 and p < 0.05 were
      considered statistically significant. Results: While maternal age and gravidity
      were similar in both groups (p > 0.05), the mean myoma diameter was smaller and
      the duration of operation was longer in the group who underwent cesarean
      myomectomy (p < 0.05). The reduction in hemoglobin level, rate of complications,
      and number of transfusions were similar in both groups (p > 0.05). Conclusion:
      This study shows that myomectomy during cesarean section does not increase
      complications or transfusion rates and appears to be a safe procedure.

PMID- 29200478
TI  - Submission to Publication Demystified: A Guide for Authors.

PMID- 29200477
TI  - Evolutionary algorithm optimization of biological learning parameters in a
      biomimetic neuroprosthesis.
AB  - Biomimetic simulation permits neuroscientists to better understand the complex
      neuronal dynamics of the brain. Embedding a biomimetic simulation in a closed
      loop neuroprosthesis, which can read and write signals from the brain, will
      permit applications for amelioration of motor, psychiatric, and memory-related
      brain disorders. Biomimetic neuroprostheses require real-time adaptation to
      changes in the external environment, thus constituting an example of a dynamic
      data-driven application system. As model fidelity increases, so does the number
      of parameters and the complexity of finding appropriate parameter configurations.
      Instead of adapting synaptic weights via machine learning, we employed major
      biological learning methods: spike-timing dependent plasticity and reinforcement
      learning. We optimized the learning metaparameters using evolutionary algorithms,
      which were implemented in parallel and which used an island model approach to
      obtain sufficient speed. We employed these methods to train a cortical spiking
      model to utilize macaque brain activity, indicating a selected target, to drive a
      virtual musculoskeletal arm with realistic anatomical and biomechanical
      properties to reach to that target. The optimized system was able to reproduce
      macaque data from a comparable experimental motor task. These techniques can be
      used to efficiently tune the parameters of multiscale systems, linking realistic
      neuronal dynamics to behavior, and thus providing a useful tool for neuroscience
      and neuroprosthetics.

PMID- 29200480
TI  - STITCHLESS Percutaneous Endoscopic Cervical Discectomy: Are We Moving Towards Day
      Care Discectomy Procedure?
AB  - Background: STITCHLESS percutaneous endoscopic cervical discectomy s[PECD] is
      safe, precise, targeted, and a complete endoscopic procedure to treat soft
      cervical disc herniation with unilateral radiculopathy. It allows direct
      visualization of herniated fragment and its removal, inspection of decompressed
      nerve root in an awake and aware patient. It reduces the risk related to general
      anesthesia and to the neurological structures. However, all the patients treated
      with PECD can be candidates for anterior cervical discectomy and fusion (ACDF).
      ACDF requires a longer period of stay, expense, and more risk to neurological
      structures and ultimately loss of the disc space by fusion. Materials and
      Methods: Twenty consecutively treated patients by sPECD over a period of 2 years
      with soft cervical disc herniation and unilateral radiculopathy were included in
      the study. PECD enables removal of offending fragment under vision and irrigation
      and ablation of inflammation with few complications. All patients were followed
      for minimum of 6 months with visual analog score (VAS) and neck disability index
      (NDI). Results: All treated patients had a good outcome in terms of pain relief
      (VAS) and functional recovery (NDI). One patient had episodes of cough lying in
      the supine position and another patient had transient hoarseness of voice, (both
      recovered). Conclusion: Potential benefits of sPECD include safety as it is done
      under local anesthesia, smaller incision, short hospitalization, fewer
      complications, avoidance of fusion, preservation of segmental motion, preventing
      the adjacent segment degeneration, and avoidance of the risk related to the
      hardware (nonunion and pseudarthrosis). sPECD is an effective treatment modality
      for soft cervical disc herniation.

PMID- 29200479
TI  - Management of Sub-axial Cervical Spine Injuries.
AB  - Sub-axial cervical spine injuries are commonly seen in patients with blunt
      trauma. They may be associated with spinal cord injury resulting in tetraplegia
      and severe permanent disability. Immobilization of the neck, maintenance of blood
      pressure and oxygenation, rapid clinical and radiological assessment of all
      injuries, and realignment of the spinal column are the key steps in the emergency
      management of these injuries. The role of intravenous methylprednisolone
      administration in acute spinal cord injuries remains controversial. The
      definitive management of these injuries is based upon recognition of the fracture
      pattern, assessment of the degree of instability, the presence or absence of
      neurologic deficit, and other patient related factors that may influence the
      outcome. Nonoperative treatment comprises of some form of external immobilization
      for 8 to 12 weeks, followed by imaging to assess fracture healing, and to rule
      out instability. The goals of surgery are realignment of the vertebral column,
      decompression of the neural elements and instrumented stabilization.

PMID- 29200481
TI  - Cervical Laminectomy with Lateral Mass Screw Fixation in Cervical Spondylotic
      Myelopathy: Neurological and Sagittal Alignment Outcome: Do We Need Lateral Mass
      Screws at each Segment?
AB  - Background: Anterior cervical decompression and fusion is the standard procedure
      used for treating patients with cervical myelopathy. However, these procedures
      are associated with complications such as pseudarthrosis, construct failure, and
      neurological complications. Posterior cervical laminectomy and instrumentation is
      an alternative procedure to treat multilevel cervical myelopathy. In this study,
      we raised questions whether instrumentation is required at all levels and whether
      stabilizing the spine in neutral or lordotic contour with indirect decompression
      leads to neurological improvement with radiological evidence of anterior
      decompression. The results of posterior cervical laminectomy and instrumentation
      with lateral mass screw in terms of radiological and functional outcome in
      patients with multilevel cervical myelopathy are prospectively evaluated.
      Materials and Methods: In this prospective study conducted between June 2006 and
      December 2015, we have evaluated 112 patients with multilevel cervical myelopathy
      who underwent multilevel cervical laminectomy and instrumentation with lateral
      mass screw. All patients were evaluated preoperatively and postoperatively with
      Nurick's grading and Modified Japanese Orthopaedic Association (mJOA) scale for
      neurological function. Cooper scale and British Medical Research Council grading
      system for motor function. Curvature index was used to measure the alignment of
      cervical spine preoperatively and postoperatively. Alignment of the cervical
      spine was done preoperatively and postoperatively by calculating the curvature
      index. Axial MRI was used to calculate the severity of compression preoperatively
      which was calculated as per Singh's criteria and postoperatively to assess the
      adequacy of decompression at the operated level. Results: In our study, there
      were 112 patients including 99 males and 13 females, with mean age of 59.53
      years. The mean duration of followup of patients was 33.24 months. In total,
      cervical laminectomy was performed at 342 levels in 112 patients with an average
      of 3.05 laminectomies, and in total, 112 lateral mass screws were inserted. On
      postoperative followup, the mJOA and Nurick's grading showed improvement in all
      cases as compared to preoperative findings. The mean mJOA improved significantly
      from 8.56 preoperatively to 13.57 postoperatively (P < 0.001). The mean Nurick's
      grading also improved significantly from 2.59 preoperatively to 0.66
      postoperatively (P < 0.001). The mean Cooper scale also showed significant
      improvement in both upper and lower limbs postoperatively (P < 0.001). The mean
      preoperative Cooper scale was 1.75 and postoperative was 0.31 for upper limbs,
      and the mean Cooper scale was 2.14 preoperatively and 0.56 postoperatively for
      lower limbs. X-rays done on routine followups showed good alignment of the
      cervical spine with maintenance of curvature index in all patients. The mean
      grade of compression as seen on preoperative MRI was 2.46 which reduced
      significantly postoperatively to 0.16 (P < 0.001). Conclusion: The multilevel
      cervical laminectomy and instrumentation with lateral mass screw for multilevel
      cervical myelopathy is a safe technique that provides decompression of the spinal
      cord, prevents the development of kyphotic spinal deformity and posterior tension
      band of the spinal cord as associated with laminoplasty or uninstrumented
      laminectomy.

PMID- 29200482
TI  - Computer Simulation of Two-level Pedicle Subtraction Osteotomy for Severe
      Thoracolumbar Kyphosis in Ankylosing Spondylitis.
AB  - Background: Advanced ankylosing spondylitis is often associated with
      thoracolumbar kyphosis, resulting in an abnormal spinopelvic balance and pelvic
      morphology. Different osteotomy techniques have been used to correct AS
      deformities, unfortunnaly, not all AS patients can gain spinal sagittal balance
      and good horizontal vision after osteotomy. Materials and Methods: Fourteen
      consecutive AS patients with severe thoracolumbar kyphosis who were treated with
      two-level PSO were studied retrospectively. All were male with a mean age of 34.9
      +/- 9.6 years. The followup ranged from 1-5 years. Preoperative computer
      simulations using the Surgimap Spinal software were performed for all patients,
      and the osteotomy level and angle determined from the computer simulation were
      used surgically. Spinal sagittal parameters were measured preoperatively, after
      the computer simulation, and postoperatively and included thoracic kyphosis (TK),
      lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence, pelvic tilt
      (PT), and sacral slope (SS). The level of correlation between the computer
      simulation and postoperative parameters was evaluated, and the differences
      between preoperative and postoperative parameters were compared. The visual
      analog scale (VAS) for back pain and clinical outcome was also assessed. Results:
      Six cases underwent PSO at L1 and L3, five cases at L2 and T12, and three cases
      at L3 and T12. TK was corrected from 57.8 +/- 15.2 degrees  preoperatively to
      45.3 +/- 7.7 degrees  postoperatively (P < 0.05), LL from 9.3 +/- 17.5 degrees 
      to -52.3 +/- 3.9 degrees  (P < 0.001), SVA from 154.5 +/- 36.7 to 37.8 +/- 8.4 mm
      (P < 0.001), PT from 43.3 +/- 6.1 degrees  to 18.0 +/- 0.9 degrees  (P < 0.001),
      and SS from 0.8 +/- 7.0 degrees  to 26.5 +/- 10.6 degrees  (P < 0.001). The LL,
      VAS, and PT of the simulated two-level PSO were highly consistent with, or almost
      the same as, the postoperative parameters. The correlations between the computer
      simulations and postoperative parameters were significant. The VAS decreased
      significantly from 6.1 +/- 1.9 to 2.0 +/- 1.1 (P < 0.001). In terms of clinical
      outcome, 10 cases were graded "excellent" and 4 cases were graded "good."
      Conclusion: Two-level PSO using a preoperative computer simulation is a feasible,
      safe, and effective technique for the treatment of severe thoracolumbar kyphosis
      in AS patients with normal cervical motion.

PMID- 29200483
TI  - Biomechanical Analysis of Range of Motion and Failure Characteristics of
      Osteoporotic Spinal Compression Fractures in Human Cadaver.
AB  - Background: Vertebroplasty is a treatment for osteoporotic vertebral compression
      fractures. The optimal location of needle placement for cement injection remains
      a topic of debate. As such, the authors assessed the effects of location of two
      types of cement instillations. In addition, the motion and failure modes at the
      index and adjacent segments were measured. Materials and Methods: Seven human
      osteoporotic cadaver spines (T1-L4), cut into four consecutive vertebral
      segments, were utilized. Of these, following the exclusion of four specimens not
      suitable to utilize for analysis, a total of 24 specimens were evaluable.
      Segments were randomly assigned into four treatment groups: unipedicular and
      bipedicular injections into the superior quartile or the anatomic center of the
      vertebra using confidence (Confidence Spinal Cement System(r), DePuy Spine,
      Raynham, MA, USA) or polymethyl methacrylate. The specimens were subjected to
      nondestructive pure moments of 5 Nm, in 2.5 Nm increments, using pulleys and
      weights to simulate six degrees of physiological motion. A follower preload of
      200 N was applied in flexion extension. Testing sequence: range of motion (ROM)
      of intact specimen, fracture creation, cement injection, ROM after cement, and
      compression testing until failure. Nonconstrained motion was measured at the
      index and adjacent levels. Results: At the index level, no significant
      differences were observed in ROM in all treatment groups (P > 0.05). There was a
      significant increase in adjacent level motion only for the treatment group that
      received a unipedicular cement injection at the anatomic center. Conclusion: The
      location of the needle (superior or central) and treatment type (unipedicular or
      bipedicular) had no significant effect on the ROM at the index site. At the
      adjacent levels, a significant increase occurred with therapy through a
      unipedicular approach into the centrum of the vertebra at the treated segment.

PMID- 29200484
TI  - Treatment of Femoroacetabular Impingement with a Mini-open Direct Anterior
      Approach.
AB  - Background: The opinion about best methods of femoroacetabular impingement (FAI)
      treatment are not consistent. Operative treatment of this condition may be
      arthroscopic, but open procedures with osteotomy of the greater trochanter and
      hip dislocation has been used. The present study evaluates the benefits of the
      mini-open direct anterior approach (DAA) in treating patients with FAI, with is a
      procedure available for most orthopedic surgeons. Materials and Methods: 39
      patients treated for FAI (25 men and 14 women) at an average age of 29.3 years
      (range 18-46 years) were reviewed in this retrospective study. The mean followup
      was 45 months, (range 24-55 months). The hip impingement test was positive in all
      patients. The diagnosis of FAI was confirmed on anteroposterior and lateral hip
      view radiographs. All patients were operated with mini-open DAA. The outcomes
      were assessed with the Harris Hip Score, Short-Form 36 Health Survey and VAS
      score. Preoperative osteoarthritis was assessed according to Tonnis score.
      Results: At the final followup, improvement was noted compared to preoperative
      status in Harris Hip Score (P < 0.00001), visual analog scale score (P < 0.001),
      and Short-Form-36 score (P < 0.001). Nineteen patients returned to their previous
      sports activities. No major complications occurred. One patient developed
      heterotopic ossification and three patients developed temporary postoperative
      meralgia paresthetica. Five patients from the treatment group required total hip
      arthroplasty for severe osteoarthritis. Conclusions: Mini-open DAA is a safe and
      effective procedure for the treatment of FAI that gives good relief of symptoms
      and allows a successful return to preoperative activity levels. Further research
      with a longer followup period is needed to evaluate the influence of surgery on
      natural history of FAI.

PMID- 29200485
TI  - Clinical Outcomes of an Initial 3-month Trial of Conservative Treatment for
      Femoroacetabular Impingement.
AB  - Background: Femoroacetabular impingement (FAI) can be managed either
      conservatively or by a surgical correction of the deformity causing impingement.
      However, there is insufficient evidence to justify an immediate surgical
      treatment in all symptomatic patients, and the role of a nonoperative treatment
      is unclear. This study evaluates the role of conservative treatment for FAI.
      Materials and Methods: 87 patients (102 hips) diagnosed as FAI between January
      2011 and May 2012 were included in this retrospective study. All patients
      underwent an initial 3-month conservative treatment followed by arthroscopic hip
      surgery if symptoms did not improve. Clinical outcome scores (modified Harris Hip
      Score, nonarthritic hip score, and Western Ontario and McMaster Universities
      Arthritis Index) were evaluated at baseline and at the end of followup, and
      scores were compared between the nonsurgical and surgical groups. Results: The
      final analysis included 83 patients (55 men, 28 women; 97 hips) because four
      patients were lost to followup. The average age was 45.1 years and 14 patients
      had bilateral symptomatic FAI. After an initial conservative treatment averaging
      27.5 months (range 24-36 months), 53 hips (54.6%) could perform normal daily
      activities. The nonsurgical group had significant improvements in all clinical
      scores at the end of followup (P < 0.001). Forty four hips (45.4%) were
      unresponsive to conservative treatment and underwent arthroscopic hip surgery
      with subsequent significant improvements in clinical scores (P < 0.001). At the
      end of followup, there were no significant differences in clinical scores between
      the two groups. Conclusion: An initial trial of conservative treatment of
      sufficient length should be considered for FAI patients before surgical
      intervention.

PMID- 29200486
TI  - A Minimally Invasive Technique Using a Modified Stoppa Approach for
      Periacetabular Osteotomy: A Preliminary Cadaveric Study.
AB  - Background: Developmental hip dysplasia is diagnosed when the femoral head is not
      sufficiently covered by the acetabulum. Anterior and lateral cover deficiency is
      seen, as a result a dysplastic hip joint. Various incision modifications have
      been developed because of the muscle dissection and wide wound scar in Smith
      Peterson incision, which was originally used in Bernese osteotomy. This study
      evaluates applicability of the modified Stoppa approach in the performance of
      Bernese periacetabular osteotomy (PAO). Materials and Methods: Ten hemipelvises
      of five donor cadavers were used. The transverse Stoppa incision was made 2 cm
      over the symphysis pubis for quadrilateral surface exposure and pubic and ischial
      bone osteotomies. The second skin incision, a few centimeters lateral to the
      original incision, was made along the tensor fascia lata. Iliac bone osteotomy
      was performed starting just above the rectus femoris insertion. The displacement
      of the osteotomy was measured clinically and radiographically. Results: The mean
      anterior coverage calculated with center-edge angle was improved from 22.8
      degrees  +/-2.8 (range 20 degrees  min-28 degrees  max) preoperatively to 44.1
      degrees  +/- 3.7 (range 36 degrees  min-48 degrees  max). The displacement of the
      osteotomy at the iliopectineal line calculated on the iliac inlet view
      radiographs was 22.1 +/- 3.4 mm (range 15 mm min-26 mm max). The clinical amount
      of the anterior displacement on the cadavers was 17.8 +/- 3.35 mm (range 11 mm-21
      mm) and lateral displacement was 20.3 +/- 3.23 mm (range 15 mm-24 mm). The amount
      of the posterior intact bone enlargement at the quadrilateral surface was 5.3 +/-
      0.48 mm. Conclusion: This less traumatic two-incision exposure is an adequate
      technique for Bernese PAO, allowing the bone to be cut under direct visual
      observation and reducing the need to use fluoroscopy.

PMID- 29200487
TI  - Morton's Neuroma (Interdigital Neuralgia) Treated with Metatarsal Sliding
      Osteotomy.
AB  - Background: Morton's neuroma is a common cause of metatarsalgia and many
      treatments had been described in literature. However, there have been only a few
      reports that treat the neuroma with an osteotomy on the proximal, not distal
      portion of the metatarsal bone using a plate. This study describes the clinical
      outcome of sliding osteotomy on the proximal metatarsal bone for the treatment of
      Morton's neuroma. Materials and Methods: Sixty five consecutive patients (85
      feet) who underwent surgery for Morton's neuroma between November 2010 and
      February 2013 were identified from hospital records to include in this
      retrospective study. Average followup period was 37.3 months (range 24-51
      months). Mean patient age at surgery was 50.2 years (range 23-75 years).
      Metatarsal sliding osteotomies were only performed on the third metatarsal bone.
      Clinical evaluations with the American Orthopaedic Foot and Ankle Society Lesser
      Metatarsophalangeal Interphalangeal Scale (AOFAS LMIS) and Foot Function Index
      (FFI) were performed. The length of the lesser toe was measured for radiologic
      evaluation. Results: Postoperatively, AOFAS LMIS and FFI were improved from 52.1
      (range 45-60) and 62.4 (range 54-73) to 74.2 (range 68-86) and 31.3 (range 26
      37). At the last followup, preoperative pain was dissolved in 79 feet (93% of
      overall 85 feet). A shortened 3.2 mm (+/-1.1) metatarsal bone following osteotomy
      was radiographically measured. There were six cases of complications (soft tissue
      infection, early numbness, delayed union, limitation of dorsiflexion and metal
      failure, etc.). Conclusions: This proximal metatarsal sliding osteotomy can be a
      relatively effective operative method in relieving pain from Morton's neuroma.

PMID- 29200488
TI  - A Newly Designed Intramedullary Nail for the Treatment of Diaphyseal Forearm
      Fractures in Adults.
AB  - Background: The treatment of diaphyseal forearm fractures using open reduction
      and plate fixation is generally accepted as the best choice in many studies.
      However, periosteal stripping, haematoma evacuation may result in delayed union,
      nonunion and infection. Refracture after plate removal is another concern. To
      overcome these problems intramedullary nails (IM) with different designs have
      been used with various outcomes. However previous IM nails have some shortcomings
      such is rotational instability and interlocking difficulties. We evaluated the
      results of newly designed IM nail in the treatment of diaphyseal forearm
      fractures in adults. Materials and Methods: 32 patients who had been treated with
      the interlocking IM nail for forearm fractures between 2011 and 2014 were
      included in this study. There were 23 males and 9 females with mean age of 36
      years (range 18-68 years). 22 patients (68.8%) had both bone fractures. Nine
      patients (28.1%) had open fractures. The remaining ten patients (31.2%) had
      radius or ulna fractures. Grace and Eversmann rating system was used to assess
      functional evaluation. Patient reported outcomes were assessed using the
      Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores. Results:
      Union was achieved in all patients. The mean followup was 17 months (range 13 -
      28 months). According to the Grace-Eversmann criteria, 27 patients (87.5%) had
      excellent or good results. The mean DASH score was 14 (range 5-36). Overall
      complication rate was 12.5%. Superficial infection was encountered in two
      patients. One patient had delayed union, however fracture healed without any
      additional surgical procedure. One patient who had open grade 3A, comminuted
      proximal third radius fracture developed radioulnar synostosis. Conclusions: The
      new design IM interlocking forearm nail provides satisfactory functional and
      radiological outcomes in the treatment of adult diaphyseal forearm fractures.

PMID- 29200489
TI  - Flexion Deformities of the Wrist and Fingers in Spastic Cerebral Palsy: A
      Protocol of Management.
AB  - Background: Literature is confusing regarding grading and treatment of flexion
      deformities of wrist and fingers in spastic cerebral palsy (CP). The most
      established classification is that described by Zancolli; unfortunately, it has
      its shortcomings which we experienced in the beginning of our approach to manage
      this rather difficult deformity. We thus modified Zancolli's classification and
      developed a classification system and treatment protocol. Materials and Methods:
      Thirty patients with spastic CP were operated upon due to flexion deformity of
      the wrist and fingers and were included in this study. Age ranged from 4 to 14
      years, average 7 years. There were twenty boys and ten girls. Results: The
      average followup was 18 months (range 9 months - 3 years). The power of wrist
      dorsiflexion, the "House's classification of upper extremity functional use" and
      the clinical assessment of hand function were used for evaluation; they improved
      in all patients and this improvement was statistically significant. In all
      patients, cosmetic appearance improved without any residual flexion deformity.
      Conclusion: This study introduces a new grading system for flexion deformity of
      wrist and fingers in spastic CP that correlates with severity of the condition
      and allows a treatment protocol to be established.

PMID- 29200490
TI  - Management of Nail Bed Injuries Associated with Fingertip Injuries.
AB  - Background: Management of nail injuries can often be a challenging experience,
      especially in presence of complex fingertips' injuries that include soft tissue
      loss and distal phalanx injury. Most studies found in the literature focus on
      individual injuries and describe methods to tackle those injuries,
      notwithstanding the fact that the nail, nailbed, distal phalanx, soft tissue and
      skin of the finger tip form a complex and often more than one element of this
      complex is injured. This retrospective study therefore focuses on the management
      of nail bed injuries as a part of the complex finger tip injury and outlines the
      surgical principles and techniques that were used in their management. Materials
      and Methods: Two hundred and forty patients from a tertiary care center in
      different clinical settings where a wide variety of cases involving the nail bed
      injuries were included in this study. Patients comprised of 192 (80%) males and
      48 (20%) females with the average male age of 37.3 years (range 1-66 years) and
      average female age of 29 years (range 1-59 years). 210 patients had single finger
      involment, 30 patients had two finger involvement (total fingers involved- 270).
      The middle finger was most commonly involved while the index finger was the
      second most commonest finger involved. In 198 (89.18%) patients local anaesthesia
      was used while in the rest: regional blocks [n = 10 (4.5%)] and general
      anaesthesia [n = 14 (6.3%)] were used. Results: In this retrospective study, out
      of the total of two hundred and forty patients, 222 (92.5%) patients underwent
      surgery, while the rest 18 (7.5%) were treated conservatively. Two hundred and
      ten patients who underwent surgery had complete healing over the course of
      treatment and followup, while four patients needed secondary interventional.
      Eight patients who had surgery were migrant workers were lost to follow up after
      surgery. Eight patients had postoperative complications that included infection,
      secondary necrosis, wound breakdown and non healing fractures. Conclusion:
      Accurate and timely diagnosis of nail bed injury and its meticulous repair is
      cardinal to the management of any nail bed injury. However all nail bed injuries
      must be seen in the context of associated injuries of the finger tip complex,
      namely skin, soft tissue and distal phalanx injuries. Fixation of associated bony
      injury which closely underlines the nail bed and provides physical support to the
      nail bed along with correction of soft tissue injuries in the form of flaps or
      grafts, compounded by the repair or replacement of nail plate in the first 24
      hours.

PMID- 29200491
TI  - Metallosis: A Complication in the Guided Growing Rod System Used in Treatment of
      Scoliosis.
AB  - Soft tissue reaction following metallic debris formation with the use of guided
      growing rod system has not been previously reported in human. The purpose of this
      study is to report complications caused by metallosis in a guided growing rod
      system. A 9-year-old female patient, who underwent treatment for the progressive
      idiopathic scoliosis (with Cobb's angle of 71 degrees ) with the guided growing
      rod system. Her Cobb's angle was corrected to 13 degrees  with the index surgery.
      During the 5 years postoperative period, she manifested recurrent episodes of
      skin irritation and progressive worsening of lateral curvature of the spine to an
      angle of 57 degrees . Furthermore, at her final followup, Risser stage 4 with a
      gain in height of 26.4 cm was achieved. Considering adequate growth attainment
      and deterioration in the curvature, revision surgery with fusion was performed.
      Postoperative Cobb's angle of 23 degrees  was achieved with the final correction.
      During the revisional surgery, signs of implant wear and metallosis were observed
      at the location of the unconstrained screws. On histological evaluation, chronic
      inflammation with foreign body granules was seen. However, titanium level in the
      body was within normal range. She was discharged without any complications. More
      research on implant wear as a complication in the guided growing rod system is
      necessary before its widespread use. The occurrence of metallosis with the use of
      guided growing rod system in growing young children should be considered, when
      designing the implants.

PMID- 29200492
TI  - Effective Medical Writing: How to Write a Case Report Which Editors Would
      Publish.

PMID- 29200493
TI  - Author's Reply.

PMID- 29200494
TI  - Legends of Indian Orthopedics: Dr. Brij Bhushan Joshi.

PMID- 29200495
TI  - Erratum: Current Concepts in Sports Injury Rehabilitation.
AB  - [This corrects the article on p. 529 in vol. 51, PMID: 28966376.].

PMID- 29200496
TI  - A national-scale model of linear features improves predictions of farmland
      biodiversity.
AB  - Modelling species distribution and abundance is important for many conservation
      applications, but it is typically performed using relatively coarse-scale
      environmental variables such as the area of broad land-cover types. Fine-scale
      environmental data capturing the most biologically relevant variables have the
      potential to improve these models. For example, field studies have demonstrated
      the importance of linear features, such as hedgerows, for multiple taxa, but the
      absence of large-scale datasets of their extent prevents their inclusion in large
      scale modelling studies.We assessed whether a novel spatial dataset mapping
      linear and woody-linear features across the UK improves the performance of
      abundance models of 18 bird and 24 butterfly species across 3723 and 1547 UK
      monitoring sites, respectively.Although improvements in explanatory power were
      small, the inclusion of linear features data significantly improved model
      predictive performance for many species. For some species, the importance of
      linear features depended on landscape context, with greater importance in
      agricultural areas. Synthesis and applications. This study demonstrates that a
      national-scale model of the extent and distribution of linear features improves
      predictions of farmland biodiversity. The ability to model spatial variability in
      the role of linear features such as hedgerows will be important in targeting agri
      environment schemes to maximally deliver biodiversity benefits. Although this
      study focuses on farmland, data on the extent of different linear features are
      likely to improve species distribution and abundance models in a wide range of
      systems and also can potentially be used to assess habitat connectivity.

PMID- 29200497
TI  - Sweat bees on hot chillies: provision of pollination services by native bees in
      traditional slash-and-burn agriculture in the Yucatan Peninsula of tropical
      Mexico.
AB  - Traditional tropical agriculture often entails a form of slash-and-burn land
      management that may adversely affect ecosystem services such as pollination,
      which are required for successful crop yields. The Yucatan Peninsula of Mexico
      has a >4000 year history of traditional slash-and-burn agriculture, termed
      'milpa'. Hot 'Habanero' chilli is a major pollinator-dependent crop that nowadays
      is often grown in monoculture within the milpa system.We studied 37 local
      farmers' chilli fields (sites) to evaluate the effects of landscape composition
      on bee communities. At 11 of these sites, we undertook experimental pollination
      treatments to quantify the pollination of chilli. We further explored the
      relationships between landscape composition, bee communities and pollination
      service provision to chilli.Bee species richness, particularly species of the
      family Apidae, was positively related to the amount of forest cover. Species
      diversity decreased with increasing proportion of crop land surrounding each
      sampling site. Sweat bees of the genus Lasioglossum were the most abundant bee
      taxon in chilli fields and, in contrast to other bee species, increased in
      abundance with the proportion of fallow land, gardens and pastures which are an
      integral part of the milpa system.There was an average pollination shortfall of
      21% for chilli across all sites; yet the shortfall was unrelated to the
      proportion of land covered by crops. Rather, chilli pollination was positively
      related to the abundance of Lasioglossum bees, probably an important pollinator
      of chilli, as well indirectly to the proportion of fallow land, gardens and
      pastures that promote Lasioglossum abundance. Synthesis and applications.
      Current, low-intensity traditional slash-and-burn (milpa) agriculture provides
      Lasioglossum spp. pollinators for successful chilli production; fallow land,
      gardens and pasture therefore need to be valued as important habitats for these
      and related ground-nesting bee species. However, the negative impact of
      agriculture on total bee species diversity highlights how agricultural
      intensification is likely to reduce pollination services to crops, including
      chilli. Indeed, natural forest cover is vital in tropical Yucatan to maintain a
      rich assemblage of bee species and the provision of pollination services for
      diverse crops and wild flowers.

PMID- 29200498
TI  - A Teaching Experiment to Elucidate a Cation-pi Effect in an Alkyne Cycloaddition
      Reaction and Illustrate Hypothesis Driven Design of Experiments.
AB  - An organic chemistry experiment is described that is based on recent research to
      elucidate a novel cation-pi interaction between tetraalkammonium cations and
      propargyl hydrazines. This non-bonded interaction is a key component of the
      mechanism of ammonium-catalyzed intramolecular cycloaddition of nitrogen to the
      terminal carbon of a C-C triple bond of the propargyl substrate. In this teaching
      experiment, reactions and control experiments are employed to demonstrate the
      testing of two alternative mechanistic hypotheses. Specifically, cyclization
      reactions are performed with a soluble base (sodium phenoxide) with and without
      tetrabutylammonium bromide under homogeneous conditions. Students observe that
      the added ammonium salt accelerates the reaction. They are then encouraged to
      develop a testable hypothesis for the role of the ammonium salt in the
      cyclization mechanism: typical phase transfer or other. IR spectroscopy is then
      used to directly observe a dose dependent shift of the alkyne stretching mode due
      to a cation-pi interaction. In this experiment, undergraduate "researchers" were
      able to practice the scientific method on a contemporary system and see how data
      are generated and interpreted to adjudicate between rival hypotheses in a way
      that emulates authentic and current research in a lab setting. This experimental
      design was tested on students enrolled in the introductory undergraduate Organic
      Chemistry Lab.

PMID- 29200499
TI  - Coarse-graining and hybrid methods for efficient simulation of stochastic multi
      scale models of tumour growth.
AB  - The development of hybrid methodologies is of current interest in both multi
      scale modelling and stochastic reaction-diffusion systems regarding their
      applications to biology. We formulate a hybrid method for stochastic multi-scale
      models of cells populations that extends the remit of existing hybrid methods for
      reaction-diffusion systems. Such method is developed for a stochastic multi-scale
      model of tumour growth, i.e. population-dynamical models which account for the
      effects of intrinsic noise affecting both the number of cells and the
      intracellular dynamics. In order to formulate this method, we develop a coarse
      grained approximation for both the full stochastic model and its mean-field
      limit. Such approximation involves averaging out the age-structure (which
      accounts for the multi-scale nature of the model) by assuming that the age
      distribution of the population settles onto equilibrium very fast. We then couple
      the coarse-grained mean-field model to the full stochastic multi-scale model. By
      doing so, within the mean-field region, we are neglecting noise in both cell
      numbers (population) and their birth rates (structure). This implies that, in
      addition to the issues that arise in stochastic-reaction diffusion systems, we
      need to account for the age-structure of the population when attempting to couple
      both descriptions. We exploit our coarse-graining model so that, within the mean
      field region, the age-distribution is in equilibrium and we know its explicit
      form. This allows us to couple both domains consistently, as upon transference of
      cells from the mean-field to the stochastic region, we sample the equilibrium age
      distribution. Furthermore, our method allows us to investigate the effects of
      intracellular noise, i.e. fluctuations of the birth rate, on collective
      properties such as travelling wave velocity. We show that the combination of
      population and birth-rate noise gives rise to large fluctuations of the birth
      rate in the region at the leading edge of front, which cannot be accounted for by
      the coarse-grained model. Such fluctuations have non-trivial effects on the wave
      velocity. Beyond the development of a new hybrid method, we thus conclude that
      birth-rate fluctuations are central to a quantitatively accurate description of
      invasive phenomena such as tumour growth.

PMID- 29200500
TI  - Expansion of deciduous tall shrubs but not evergreen dwarf shrubs inhibited by
      reindeer in Scandes mountain range.
AB  - One of the most palpable effects of warming in Arctic ecosystems is shrub
      expansion above the tree line. However, previous studies have found that reindeer
      can influence plant community responses to warming and inhibit shrubification of
      the tundra.We revisited grazed (ambient) and ungrazed study plots (exclosures),
      at the southern as well as the northern limits of the Swedish alpine region, to
      study long-term grazing effects and vegetation changes in response to increasing
      temperatures between 1995 and 2011, in two vegetation types (shrub heath and
      mountain birch forest).In the field layer at the shrub heath sites, evergreen
      dwarf shrubs had increased in cover from 26% to 49% but were unaffected by
      grazing. Deciduous dwarf and tall shrubs also showed significant, though smaller,
      increases over time. At the birch forest sites, the increase was similar for
      evergreen dwarf shrubs (20-48%) but deciduous tall shrubs did not show the same
      consistent increase over time as in the shrub heath.The cover and height of the
      shrub layer were significantly greater in exclosures at the shrub heath sites,
      but no significant treatment effects were found on species richness or
      diversity.July soil temperatures and growing season thawing degree days (TDD)
      were higher in exclosures at all but one site, and there was a significant
      negative correlation between mean shrub layer height and soil TDD at the shrub
      heath sites. Synthesis. This study shows that shrub expansion is occurring
      rapidly in the Scandes mountain range, both above and below the tree line. Tall,
      deciduous shrubs had benefitted significantly from grazing exclosure, both in
      terms of cover and height, which in turn lowered summer soil temperatures.
      However, the overriding vegetation shift across our sites was the striking
      increase in evergreen dwarf shrubs, which were not influenced by grazing. As the
      effects of an increase in evergreen dwarf shrubs and more recalcitrant plant
      litter may to some degree counteract some of the effects of an increase in
      deciduous tall shrubs, herbivore influence on shrub interactions is potentially
      of great importance for shaping arctic shrub expansion and its associated
      ecosystem effects.

PMID- 29200501
TI  - A tutorial on bridge sampling.
AB  - The marginal likelihood plays an important role in many areas of Bayesian
      statistics such as parameter estimation, model comparison, and model averaging.
      In most applications, however, the marginal likelihood is not analytically
      tractable and must be approximated using numerical methods. Here we provide a
      tutorial on bridge sampling (Bennett, 1976; Meng & Wong, 1996), a reliable and
      relatively straightforward sampling method that allows researchers to obtain the
      marginal likelihood for models of varying complexity. First, we introduce bridge
      sampling and three related sampling methods using the beta-binomial model as a
      running example. We then apply bridge sampling to estimate the marginal
      likelihood for the Expectancy Valence (EV) model-a popular model for
      reinforcement learning. Our results indicate that bridge sampling provides
      accurate estimates for both a single participant and a hierarchical version of
      the EV model. We conclude that bridge sampling is an attractive method for
      mathematical psychologists who typically aim to approximate the marginal
      likelihood for a limited set of possibly high-dimensional models.

PMID- 29200502
TI  - Lateral flow assay for carbohydrate antigen 19-9 in whole blood by using
      magnetized carbon nanotubes.
AB  - The authors describe a rapid, low-cost and sensitive approach for the
      determination of carbohydrate antigen 19-9 (CA 19-9) in whole blood by using
      magnetized carbon nanotube (MCNT) and lateral flow strip biosensor (LFSB). MCNTs
      were synthesized by depositing magnetite (Fe3O4) nanoparticles on multiwalled
      carbon nanotube (CNT) via co-precipitation of ferric and ferrous ions within a
      dispersion of shortened multiwalled CNTs. Antibody against CA 19-9 (Ab1) was
      covalently immobilized on the MCNTs and were used to capture CA 19-9 in blood.
      After magnetic separation, the formed MCNT-Ab1-CA 19-9 complexes are applied to
      the LFSB, in which a capture antibody (Ab2) and a secondary antibody (Ab3) are
      immobilized on the test zone and control zone of the LFSB, respectively. The
      captured MCNTs on the test zone and control zone are producing characteristic
      brown bands, and this enables CA 19-9 to be visually detected. Quantitation is
      accomplished by reading the intensities of the bands with a portable strip
      reader. Under optimized conditions, the assay has a detection limit as low as 30
      U?mL-1 of CA19-9 in blood. This is below the cutoff value (37 U mL-1) of CA 19-9.
      The assay duration for blood samples is 35 min. In our perception, the assay
      represents a rapid and low-cost tool for rapid determination of CA19-9 in blood
      that holds promise for clinical applications, particularly in limited resource
      settings.

PMID- 29200503
TI  - From Eminent Men to Excellent Universities: University Rankings as Calculative
      Devices.
AB  - Global university rankings have become increasingly important 'calculative
      devices' for assessing the 'quality' of higher education and research. Their
      ability to make characteristics of universities 'calculable' is here exemplified
      by the first proper university ranking ever, produced as early as 1910 by the
      American psychologist James McKeen Cattell. Our paper links the epistemological
      rationales behind the construction of this ranking to the sociopolitical context
      in which Cattell operated: an era in which psychology became institutionalized
      against the backdrop of the eugenics movement, and in which statistics of science
      became used to counter a perceived decline in 'great men.' Over time, however,
      the 'eminent man,' shaped foremost by heredity and upbringing, came to be
      replaced by the excellent university as the emblematic symbol of scientific and
      intellectual strength. We also show that Cattell's ranking was generative of new
      forms of the social, traces of which can still be found today in the enactment of
      'excellence' in global university rankings.

PMID- 29200504
TI  - Science Production in Germany, France, Belgium, and Luxembourg: Comparing the
      Contributions of Research Universities and Institutes to Science, Technology,
      Engineering, Mathematics, and Health.
AB  - Charting significant growth in science production over the 20th century in four
      European Union member states, this neo-institutional analysis describes the
      development and current state of universities and research institutes that
      bolster Europe's position as a key region in global science. On-going
      internationalization and Europeanization of higher education and science has been
      accompanied by increasing competition as well as collaboration. Despite the
      policy goals to foster innovation and further expand research capacity, in cross
      national and historical comparison neither the level of R&D investments nor
      country size accounts completely for the differential growth of scientific
      productivity. Based on a comprehensive historical database from 1900 to 2010,
      this analysis uncovers both stable and dynamic patterns of production and
      productivity in Germany, France, Belgium, and Luxembourg. Measured in peer
      reviewed research articles collected in Thomson Reuters' Science Citation Index
      Expanded, which includes journals in the fields of Science, Technology,
      Engineering, Mathematics, and Health, we show the varying contributions of
      different organizational forms, especially research universities and research
      institutes. Comparing the institutionalization pathways that created the
      conditions necessary for continuous and strong growth in scientific productivity
      in the European center of global science emphasizes that the research university
      is the key organizational form across countries.

PMID- 29200505
TI  - Early Miocene reef- and mudflat-associated gastropods from Makran (SE-Iran).
AB  - A new gastropod fauna of Burdigalian (early Miocene) age is described from the
      Iranian part of Makran. The fauna comprises 19 species and represents three
      distinct assemblages from turbid water coral reef, shallow subtidal soft-bottom
      and mangrove-fringed mudflat environments in the northern Indian Ocean.
      Especially the reef-associated assemblage comprises largely new species. This is
      explained by the rare occurrence of reefs along the northern margin of the
      Miocene Indian Ocean and the low number of scientific studies dealing with the
      region. In terms of paleobiogeography, the fauna corresponds well to coeval
      faunas from the Pakistani Balochistan and Sindh provinces and the Indian
      Kathiawar, Kutch and Kerala provinces. During the early Miocene, these
      constituted a discrete biogeographic unit, the Western Indian Province, which
      documents the near complete biogeographic isolation from the Proto-Mediterranean
      Sea. Some mudflat taxa might represent examples of vicariance following the
      Tethys closure. The fauna also displays little connection with coeval faunas from
      Indonesia, documenting a strong provincialism within the Indo-West Pacific Region
      during early Miocene times. Neritopsis gedrosiana sp. nov., Calliostoma irerense
      sp. nov., Calliostoma mohtatae sp. nov. and Trivellona makranica sp. nov. are
      described as new species.

PMID- 29200506
TI  - Leaf expansion in Phaseolus: transient auxin-induced growth increase.
AB  - Control of leaf expansion by auxin is not well understood. Evidence from short
      term exogenous applications and from treatment of excised tissues suggests auxin
      positively influences growth. Manipulations of endogenous leaf auxin content,
      however, suggests that, long-term, auxin suppresses leaf expansion. This study
      attempts to clarify the growth effects of auxin on unifoliate (primary) leaves of
      the common bean (Phaseolus vulgaris) by reexamining the response to auxin
      treatment of both excised leaf strips and attached leaves. Leaf strips, incubated
      in culture conditions that promoted steady elongation for up to 48 h, treated
      with 10 MUM NAA responded with an initial surge of elongation growth complete
      within 10 hours followed by insensitivity. A range of NAA concentrations from 0.1
      MUM to 300 MUM induced increased strip elongation after 24 hours and 48 hours.
      Increased elongation and epinastic curvature of leaf strips was found specific to
      active auxins. Expanding attached unifoliates treated once with aqueous auxin
      alpha-naphthalene acetic acid (NAA) at 1.0 mM showed both an initial surge in
      growth lasting 4-6 hours followed by growth inhibition sustained at least as long
      as 24 hours post treatment. Auxin-induced inhibition of leaf expansion was
      associated with smaller epidermal cell area. Together the results suggest
      increasing leaf auxin first increases growth then slows growth through inhibition
      of cell expansion. Excised leaf strips, retain only the initial increased growth
      response to auxin and not the subsequent growth inhibition, either as a
      consequence of wounding or of isolation from the plant.

PMID- 29200508
TI  - A Bayesian Network Meta-Analysis to Synthesize the Influence of Contexts of
      Scaffolding Use on Cognitive Outcomes in STEM Education.
AB  - Computer-based scaffolding provides temporary support that enables students to
      participate in and become more proficient at complex skills like problem solving,
      argumentation, and evaluation. While meta-analyses have addressed between-subject
      differences on cognitive outcomes resulting from scaffolding, none has addressed
      within-subject gains. This leaves much quantitative scaffolding literature not
      covered by existing meta-analyses. To address this gap, this study used Bayesian
      network meta-analysis to synthesize within-subjects (pre-post) differences
      resulting from scaffolding in 56 studies. We generated the posterior distribution
      using 20,000 Markov Chain Monte Carlo samples. Scaffolding has a consistently
      strong effect across student populations, STEM (science, technology, engineering,
      and mathematics) disciplines, and assessment levels, and a strong effect when
      used with most problem-centered instructional models (exception: inquiry-based
      learning and modeling visualization) and educational levels (exception: secondary
      education). Results also indicate some promising areas for future scaffolding
      research, including scaffolding among students with learning disabilities, for
      whom the effect size was particularly large (g = 3.13).

PMID- 29200509
TI  - 'Bottom dog men': Disability, Social Welfare and Advocacy in the Scottish
      Coalfields in the Interwar Years, 1918-1939.
AB  - This article connects with and builds on recent research on workmen's
      compensation and disability focussing on the Scottish coalfields between the
      wars. It draws upon a range of primary sources including coal company accident
      books, court cases and trade union records to analyse efforts to define and
      redefine disability, examining the language deployed and the agency of workers
      and their advocates. It is argued here that the workmen's compensation system
      associated disability with restricted functionality relating to work tasks and
      work environments. Disability became more visible and more closely monitored and
      this was a notably contested and adversarial terrain in Scotland in the
      Depression, where employers, workers and their collective organisations
      increasingly deployed medical expertise to support their cases regarding working
      and disabled bodies. In Scotland, the miners' trade unions emerged as key
      advocates for the disabled.

PMID- 29200507
TI  - Removal of Retained Electrospinning Solvent Prolongs Drug Release from
      Electrospun PLLA Fibers.
AB  - A major challenge in developing drug-releasing electrospun nanofibers is
      obtaining long-term drug release over many weeks with no burst release of drug.
      Here, we present new methods capable of prolonging the diffusive release of small
      molecule drugs from electrospun poly-L-lactic acid (PLLA) nanofibers. The methods
      focus on removal of retained electrospinning solvent through fiber heating,
      maintaining fibers in a laboratory setting, or a combination of these methods.
      These post-fabrication methods altered the release characteristics of a model
      small molecule drug, 6-aminonicotinamide (6AN), from PLLA fibers. Specifically,
      untreated fibers released 6AN over 9 days, and fibers that underwent a combined
      treatment of maintenance in a laboratory setting and heating released 6AN over 44
      days. The unique and simple method presented here prolongs diffusive release of a
      small molecule drug from electrospun fibers and has potential to assist in
      lengthening small molecule drug release from a variety of polymeric
      nanomaterials.

PMID- 29200512
TI  - Demand-pull and environmental innovations: Estimating the effects of innovative
      public procurement.
AB  - This paper contributes to the emerging literature on the adoption of
      environmental innovation, by investigating the so far unexplored role of
      governmental demand in stimulating 'greener' production choices. Specifically,
      the role of innovative public procurement in driving the adoption and diffusion
      of sustainable manufacturing technologies is analysed. Results, based on firm
      level data in the 28 Member States of the European Union, Switzerland and the
      USA, are obtained through non-parametric matching techniques. Those outline the
      crucial role of innovative public procurement in the uptake of environmental
      innovations. This confirms the relevance of such policy instrument in allowing
      countries to achieve a decarbonised and sustainable growth path which is
      compatible with competitiveness goals.

PMID- 29200511
TI  - What is the extension of the extended mind?
AB  - Two aspects of cognitive coupling, as brought forward in the Extended Mind
      Hypothesis, are discussed in this paper: (1) how shall the functional coupling
      between the organism and some entity in his environment be spelled out in detail?
      (2) What are the paradigmatic external entities to enter into that coupling?
      These two related questions are best answered in the light of an aetiological
      variety of functionalist argument that adds historical depth to the "active
      externalism" promoted by Clark and Chalmers and helps to counter some of the core
      criticisms levelled against this view. Under additional reference to conceptual
      parallels between the Extended Mind Hypothesis and a set of heterodox theories in
      biology-environmental constructivism, niche construction, developmental systems
      theory-an argument for the grounding of environmentally extended cognitive traits
      in evolved biological functions is developed. In a spirit that seeks to integrate
      extended functionalism with views from cognitive integration and complementarity,
      it is argued (ad 1) that instances of environmental coupling should be understood
      as being constitutive to cognitive functions in either of two distinct ways. It
      is further argued (ad 2) that the historically and systematically prior
      environmental counterparts in that coupling are features of the natural
      environment. Language and linguistically imbued artefacts are likely to have
      descended from more basic relations that have an extension over the environment.

PMID- 29200513
TI  - Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride,
      methyl, and nitrogen nucleophiles.
AB  - The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl
      pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium
      phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction
      with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively
      induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c.
      The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes
      olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9-C16 synthon for
      the antifungal agent ambruticin. Alternatively reaction of 7 with
      methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and
      e. Huisgen [3+2] cyclization of the (azidodienyl)iron complex 14e with alkynes
      afforded triazoles 25a-e.

PMID- 29200510
TI  - The interaction of soil phototrophs and fungi with pH and their impact on soil
      CO2, CO18O and OCS exchange.
AB  - The stable oxygen isotope composition of atmospheric CO2 and the mixing ratio of
      carbonyl sulphide (OCS) are potential tracers of biospheric CO2 fluxes at large
      scales. However, the use of these tracers hinges on our ability to understand and
      better predict the activity of the enzyme carbonic anhydrase (CA) in different
      soil microbial groups, including phototrophs. Because different classes of the CA
      family (alpha, beta and gamma) may have different affinities to CO2 and OCS and
      their expression should also vary between different microbial groups, differences
      in the community structure could impact the 'community-integrated' CA activity
      differently for CO2 and OCS. Four soils of different pH were incubated in the
      dark or with a diurnal cycle for forty days to vary the abundance of native
      phototrophs. Fluxes of CO2, CO18O and OCS were measured to estimate CA activity
      alongside the abundance of bacteria, fungi and phototrophs. The abundance of soil
      phototrophs increased most at higher soil pH. In the light, the strength of the
      soil CO2 sink and the CA-driven CO2-H2O isotopic exchange rates correlated with
      phototrophs abundance. OCS uptake rates were attributed to fungi whose abundance
      was positively enhanced in alkaline soils but only in the presence of increased
      phototrophs. Our findings demonstrate that soil-atmosphere CO2, OCS and CO18O
      fluxes are strongly regulated by the microbial community structure in response to
      changes in soil pH and light availability and supports the idea that different
      members of the microbial community express different classes of CA, with
      different affinities to CO2 and OCS.

PMID- 29200516
TI  - Options for financing pandemic preparedness.

PMID- 29200514
TI  - An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol,
      a high-affinity ligand for HIV-1 protease inhibitors.
AB  - An enantioselective synthesis of (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol,
      a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease
      inhibitors is described. The key steps involved a highly enantioselective
      enzymatic desymmetrization of meso-diacetate, an efficient transacetalization,
      and a highly diastereoselective reduction of a ketone. This route is amenable to
      large-scale synthesis using readily available starting materials.

PMID- 29200518
TI  - Public health round-up.

PMID- 29200517
TI  - A public health research agenda informed by guidelines in development.

PMID- 29200519
TI  - Restricting the use of sunbeds to prevent skin cancer.
AB  - Young people - especially women - are risking their health in pursuit of a tanned
      skin that they associate with celebrity, beauty and wellbeing. Tatum Anderson
      reports.

PMID- 29200520
TI  - Fatima Suleman: making medicines more widely available.
AB  - The availability of affordable medicines is a major barrier to providing high
      quality health care in many countries. Fatima Suleman talks to Fiona Fleck.

PMID- 29200521
TI  - Zika virus in semen: a prospective cohort study of symptomatic travellers
      returning to Belgium.
AB  - Objective: To prospectively monitor Zika viral loads in semen from Belgian
      travellers with confirmed Zika virus infection, who returned from the Americas
      during the 2016 Zika virus epidemic. Methods: We recruited symptomatic travellers
      consulting our clinic and we confirmed infection with either reverse
      transcriptase (RT) polymerase chain reaction (PCR) assay or virus neutralization
      test. The participants produced semen samples weekly, either at the clinic or at
      home. For the initial sample, the laboratory staff did a microscopy analysis if
      they received the sample within an hour of production. Using RT-PCR, we monitored
      Zika virus ribonucleic acid (RNA) loads in semen until we obtained two negative
      results. Findings: We detected Zika virus RNA in nine of 15 participants' semen,
      one of whom was vasectomized. The median time to loss of RNA detection in semen
      was 83 days after symptom onset (95% confidence interval, CI: 57-108). The
      longest duration of viral shedding in semen before obtaining the first negative
      RT-PCR result was 144 days after symptom onset. All of the 11 participants, for
      whom we microscopically analysed their semen, had presence of leukocytes, 10
      showed haematospermia and six showed oligospermia. These abnormalities occurred
      irrespective of Zika virus detection in semen. Conclusion: The majority of men in
      our study had detectable Zika virus RNA in their semen. We recommend that semen
      from Zika virus-infected men should be analysed with RT-PCR and that health
      professionals should advise infected men, even if they are vasectomized, about
      current recommendations for prevention of sexual transmission of the virus.

PMID- 29200522
TI  - Access to maternal health services: geographical inequalities, United Republic of
      Tanzania.
AB  - Objective: To determine if improved geographical accessibility led to increased
      uptake of maternity care in the south of the United Republic of Tanzania.
      Methods: In a household census in 2007 and another large household survey in
      2013, we investigated 22 243 and 13 820 women who had had a recent live birth,
      respectively. The proportions calculated from the 2013 data were weighted to
      account for the sampling strategy. We examined the association between the
      straight-line distances to the nearest primary health facility or hospital and
      uptake of maternity care. Findings: The percentages of live births occurring in
      primary facilities and hospitals rose from 12% (2571/22 243) and 29% (6477/22
      243), respectively, in 2007 to weighted values of 39% and 40%, respectively, in
      2013. Between the two surveys, women living far from hospitals showed a marked
      gain in their use of primary facilities, but the proportion giving birth in
      hospitals remained low (20%). Use of four or more antenatal visits appeared
      largely unaffected by survey year or the distance to the nearest antenatal
      clinic. Although the overall percentage of live births delivered by caesarean
      section increased from 4.1% (913/22 145) in the first survey to a weighted value
      of 6.5% in the second, the corresponding percentages for women living far from
      hospital were very low in 2007 (2.8%; 35/1254) and 2013 (3.3%). Conclusion: For
      women living in our study districts who sought maternity care, access to primary
      facilities appeared to improve between 2007 and 2013, however access to hospital
      care and caesarean sections remained low.

PMID- 29200523
TI  - Systematic review of dietary trans-fat reduction interventions.
AB  - Objective: To systematically review published studies of interventions to reduce
      people's intake of dietary trans-fatty acids (TFAs). Methods: We searched online
      databases (CINAHL, the CRD Wider Public Health database, Cochrane Database of
      Systematic Reviews, Ovid(r), MEDLINE(r), Science Citation Index and Scopus) for
      studies evaluating TFA interventions between 1986 and 2017. Absolute decrease in
      TFA consumption (g/day) was the main outcome measure. We excluded studies
      reporting only on the TFA content in food products without a link to intake. We
      included trials, observational studies, meta-analyses and modelling studies. We
      conducted a narrative synthesis to interpret the data, grouping studies on a
      continuum ranging from interventions targeting individuals to population-wide,
      structural changes. Results: After screening 1084 candidate papers, we included
      23 papers: 12 empirical and 11 modelling studies. Multiple interventions in
      Denmark achieved a reduction in TFA consumption from 4.5 g/day in 1976 to 1.5
      g/day in 1995 and then virtual elimination after legislation banning TFAs in
      manufactured food in 2004. Elsewhere, regulations mandating reformulation of food
      reduced TFA content by about 2.4 g/day. Worksite interventions achieved
      reductions averaging 1.2 g/day. Food labelling and individual dietary counselling
      both showed reductions of around 0.8 g/day. Conclusion: Multicomponent
      interventions including legislation to eliminate TFAs from food products were the
      most effective strategy. Reformulation of food products and other multicomponent
      interventions also achieved useful reductions in TFA intake. By contrast,
      interventions targeted at individuals consistently achieved smaller reductions.
      Future prevention strategies should consider this effectiveness hierarchy to
      achieve the largest reductions in TFA consumption.

PMID- 29200525
TI  - Mental health care during the Ebola virus disease outbreak in Sierra Leone.
AB  - Problem: Reported levels of mental health and psychosocial problems rose during
      the 2014-2015 Ebola virus disease outbreak in Sierra Leone. Approach: As part of
      the emergency response, existing plans to create mental health units within the
      existing hospital framework were brought forward. A nurse-led mental health and
      psychosocial support service, with an inpatient liaison service and an outpatient
      clinic, was set up at the largest government hospital in the country. One mental
      health nurse trained general nurses in psychological first aid, case
      identification and referral pathways. Health-care staff attended mental well
      being workshops on coping with stigma and stress. Local setting: Mental health
      service provision in Sierra Leone is poor, with one specialist psychiatric
      hospital to serve the population of 7 million. Relevant changes: From March 2015
      to February 2016, 143 patients were seen at the clinic; 20 had survived or had
      relatives affected by Ebola virus disease. Half the patients (71) had mild
      distress or depression, anxiety disorders and grief or social problems, while 30
      patients presented with psychosis requiring medication. Fourteen non-specialist
      nurses received mental health awareness training. Over 100 physicians, nurses and
      auxiliary staff participated in well-being workshops. Lessons learnt: A nurse-led
      approach within a non-specialist setting was a successful model for delivering
      mental health and psychosocial support services during the Ebola outbreak in
      Sierra Leone. Strong leadership and partnerships were essential for establishing
      a successful service. Lack of affordable psychotropic medications, limited human
      resources and weak social welfare structures remain challenges.

PMID- 29200524
TI  - Health-care workers' occupational exposures to body fluids in 21 countries in
      Africa: systematic review and meta-analysis.
AB  - Objective: To estimate the lifetime and 12-month prevalence of occupational
      exposure to body fluids among health-care workers in Africa. Methods: Embase(r),
      PubMed(r) and CINAHL databases were systematically searched for studies published
      between January 2000 and August 2017 that reported the prevalence of occupational
      exposure to blood or other body fluids among health-care workers in Africa. The
      continent-wide prevalence of exposure was estimated using random-effects meta
      analysis. Findings: Of the 904 articles identified, 65 studies from 21 African
      countries were included. The estimated pooled lifetime and 12-month prevalence of
      occupational exposure to body fluids were 65.7% (95% confidence interval, CI:
      59.7-71.6) and 48.0% (95% CI: 40.7-55.3), respectively. Exposure was largely due
      to percutaneous injury, which had an estimated 12-month prevalence of 36.0% (95%
      CI: 31.2-40.8). The pooled 12-month prevalence of occupational exposure among
      medical doctors (excluding surgeons), nurses (including midwives and nursing
      assistants) and laboratory staff (including laboratory technicians) was 46.6%
      (95% CI: 33.5-59.7), 44.6% (95% CI: 34.1-55.0) and 34.3% (95% CI: 21.8-46.7),
      respectively. The risk of exposure was higher among health-care workers with no
      training on infection prevention and those who worked more than 40 hours per
      week. Conclusion: The evidence available suggests that almost one half of health
      care workers in Africa were occupationally exposed to body fluids annually.
      However, a lack of data from some countries was a major limitation. National
      governments and health-care institutions across Africa should prioritize efforts
      to minimize occupational exposure among health-care workers.

PMID- 29200526
TI  - Uddanam nephropathy in India: a challenge for epidemiologists.

PMID- 29200527
TI  - Improving the health and well-being of children of migrant workers.

PMID- 29200528
TI  - Revisiting the horizontal redistribution of water in soils: Experiments and
      numerical modeling.
AB  - A series of experiments and related numerical simulations were carried out to
      study one-dimensional water redistribution processes in an unsaturated soil. A
      long horizontal Plexiglas box was packed as homogenously as possible with sand.
      The sandbox was divided into two sections using a very thin metal plate, with one
      section initially fully saturated and the other section only partially saturated.
      Initial saturation in the dry section was set to 0.2, 0.4, or 0.6 in three
      different experiments. Redistribution between the wet and dry sections started as
      soon as the metal plate was removed. Changes in water saturation at various
      locations along the sandbox were measured as a function of time using a dual
      energy gamma system. Also, air and water pressures were measured using two
      different kinds of tensiometers at various locations as a function of time. The
      saturation discontinuity was found to persist during the entire experiments,
      while observed water pressures were found to become continuous immediately after
      the experiments started. Two models, the standard Richards equation and an
      interfacial area model, were used to simulate the experiments. Both models showed
      some deviations between the simulated water pressures and the measured data at
      early times during redistribution. The standard model could only simulate the
      observed saturation distributions reasonably well for the experiment with the
      lowest initial water saturation in the dry section. The interfacial area model
      could reproduce observed saturation distributions of all three experiments,
      albeit by fitting one of the parameters in the surface area production term.

PMID- 29200529
TI  - Irrigation, risk aversion, and water right priority under water supply
      uncertainty.
AB  - This paper explores the impacts of a water right's allocative priority-as an
      indicator of farmers' risk-bearing ability-on land irrigation under water supply
      uncertainty. We develop and use an economic model to simulate farmers' land
      irrigation decision and associated economic returns in eastern Idaho. Results
      indicate that the optimal acreage of land irrigated increases with water right
      priority when hydroclimate risk exhibits a negatively skewed or right-truncated
      distribution. Simulation results suggest that prior appropriation enables senior
      water rights holders to allocate a higher proportion of their land to irrigation,
      6 times as much as junior rights holders do, creating a gap in the annual
      expected net revenue reaching up to $141.4 acre-1 or $55,800 per farm between the
      two groups. The optimal irrigated acreage, expected net revenue, and shadow value
      of a water right's priority are subject to substantial changes under a changing
      climate in the future, where temporal variation in water supply risks
      significantly affects the profitability of agricultural land use under the
      priority-based water sharing mechanism.

PMID- 29200530
TI  - Power Electronic Semiconductor Materials for Automotive and Energy Saving
      Applications - SiC, GaN, Ga2O3, and Diamond.
AB  - Power electronics belongs to the future key technologies in order to increase
      system efficiency as well as performance in automotive and energy saving
      applications. Silicon is the major material for electronic switches since
      decades. Advanced fabrication processes and sophisticated electronic device
      designs have optimized the silicon electronic device performance almost to their
      theoretical limit. Therefore, to increase the system performance, new materials
      that exhibit physical and chemical properties beyond silicon need to be explored.
      A number of wide bandgap semiconductors like silicon carbide, gallium nitride,
      gallium oxide, and diamond exhibit outstanding characteristics that may pave the
      way to new performance levels. The review will introduce these materials by (i)
      highlighting their properties, (ii) introducing the challenges in materials
      growth, and (iii) outlining limits that need innovation steps in materials
      processing to outperform current technologies.

PMID- 29200531
TI  - A composite smeared finite element for mass transport in capillary systems and
      biological tissue.
AB  - One of the key processes in living organisms is mass transport occurring from
      blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs,
      immune cells, and - in the reverse direction - transport of waste products of
      cell metabolism to blood vessels. The mass exchange from blood vessels to tissue
      and vice versa occurs through blood vessel walls. This vital process has been
      investigated experimentally over centuries, and also in the last decades by the
      use of computational methods. Due to geometrical and functional complexity and
      heterogeneity of capillary systems, it is however not feasible to model in silico
      individual capillaries (including transport through the walls and coupling to
      tissue) within whole organ models. Hence, there is a need for simplified and
      robust computational models that address mass transport in capillary-tissue
      systems. We here introduce a smeared modeling concept for gradient-driven mass
      transport and formulate a new composite smeared finite element (CSFE). The
      transport from capillary system is first smeared to continuous mass sources
      within tissue, under the assumption of uniform concentration within capillaries.
      Here, the fundamental relation between capillary surface area and volumetric
      fraction is derived as the basis for modeling transport through capillary walls.
      Further, we formulate the CSFE which relies on the transformation of the one
      dimensional (1D) constitutive relations (for transport within capillaries) into
      the continuum form expressed by Darcy's and diffusion tensors. The introduced
      CSFE is composed of two volumetric parts - capillary and tissue domains, and has
      four nodal degrees of freedom (DOF): pressure and concentration for each of the
      two domains. The domains are coupled by connectivity elements at each node. The
      fictitious connectivity elements take into account the surface area of capillary
      walls which belongs to each node, as well as the wall material properties
      (permeability and partitioning). The overall FE model contains geometrical and
      material characteristics of the entire capillary-tissue system, with
      physiologically measurable parameters assigned to each FE node within the model.
      The smeared concept is implemented into our implicit-iterative FE scheme and into
      FE package PAK. The first three examples illustrate accuracy of the CSFE element,
      while the liver and pancreas models demonstrate robustness of the introduced
      methodology and its applicability to real physiological conditions.

PMID- 29200532
TI  - Preparation of Diisopropylammonium Bis(catecholato)cyclohexylsilicate.

PMID- 29200533
TI  - Going to Pot? The Impact of Dispensary Closures on Crime.
AB  - Jurisdictions that sanction medical or, more recently, recreational marijuana use
      often allow retail sales at dispensaries. Dispensaries are controversial as many
      believe they contribute to local crime. To assess this claim, we analyze the
      short-term mass closing of hundreds of medical marijuana dispensaries in Los
      Angeles. Contrary to popular wisdom, we find an immediate increase in crime
      around dispensaries ordered to close relative to those allowed to remain open.
      The increase is specific to the type of crime most plausibly deterred by
      bystanders, and is correlated with neighborhood walkability. We find a similar
      pattern of results for temporary restaurant closures due to health code
      violations. A likely common mechanism is that "eyes upon the street" deter some
      types of crime.

PMID- 29200534
TI  - Spread in the magnitude of climate model interdecadal global temperature
      variability traced to disagreements over high-latitude oceans.
AB  - Unforced variability in global mean surface air temperature can obscure or
      exaggerate global warming on interdecadal timescales, thus understanding both the
      magnitude and generating mechanisms of such variability is of critical importance
      for both attribution studies as well as decadal climate prediction. Coupled
      atmosphere-ocean general circulation models (climate models) simulate a wide
      range of magnitudes of unforced interdecadal variability in global mean surface
      air temperature (UITglobal), hampering efforts to quantify the influence of
      UITglobal on contemporary global temperature trends. Recently, a preliminary
      consensus has emerged that unforced interdecadal variability in local surface
      temperatures (UITlocal) over the tropical Pacific Ocean are particularly
      influential on UITglobal. Therefore, a reasonable hypothesis might be that the
      large spread in the magnitude of UITglobal across climate models can be explained
      by the spread in the magnitude of simulated tropical Pacific UITlocal. Here we
      show that this hypothesis is mostly false. Instead, the spread in the magnitude
      of UITglobal is linked much more strongly to the spread in the magnitude of
      UITlocal over high-latitude regions characterized by significant variability in
      oceanic convection, sea ice concentration, and energy flux at both the surface
      and the top of the atmosphere (TOA). Thus, efforts to constrain the climate model
      produced range of UITglobal magnitude would be best served by focusing on the
      simulation of air-sea interaction at high latitudes.

PMID- 29200535
TI  - MJO-Related Tropical Convection Anomalies Lead to More Accurate Stratospheric
      Vortex Variability in Subseasonal Forecast Models.
AB  - The effect of the Madden-Julian Oscillation (MJO) on the Northern Hemisphere
      wintertime stratospheric polar vortex in the period preceding stratospheric
      sudden warmings is evaluated in operational subseasonal forecasting models.
      Reforecasts which simulate stronger MJO-related convection in the Tropical West
      Pacific also simulate enhanced heat flux in the lowermost stratosphere and a more
      realistic vortex evolution. The time scale on which vortex predictability is
      enhanced lies between 2 and 4 weeks for nearly all cases. Those stratospheric
      sudden warmings that were preceded by a strong MJO event are more predictable at
      ~20 day leads than stratospheric sudden warmings not preceded by a MJO event.
      Hence, knowledge of the MJO can contribute to enhanced predictability, at least
      in a probabilistic sense, of the Northern Hemisphere polar stratosphere.

PMID- 29200536
TI  - Decade-long deep-ocean warming detected in the subtropical South Pacific.
AB  - The persistent energy imbalance at the top of the atmosphere, inferred from
      satellite measurements, indicates that the Earth's climate system continues to
      accumulate excess heat. As only sparse and irregular measurements of ocean heat
      below 2000 m depth exist, one of the most challenging questions in global climate
      change studies is whether the excess heat has already penetrated into the deep
      ocean. Here we perform a comprehensive analysis of satellite and in situ
      measurements to report that a significant deep-ocean warming occurred in the
      subtropical South Pacific Ocean over the past decade (2005-2014). The local
      accumulation of heat accounted for up to a quarter of the global ocean heat
      increase, with directly and indirectly inferred deep ocean (below 2000 m)
      contribution of 2.4 +/- 1.4 and 6.1-10.1 +/- 4.4%, respectively. We further
      demonstrate that this heat accumulation is consistent with a decade-long
      intensification of the subtropical convergence, possibly linked to the persistent
      La Nina-like state.

PMID- 29200537
TI  - Bayesian Computation for Log-Gaussian Cox Processes: A Comparative Analysis of
      Methods.
AB  - The Log-Gaussian Cox Process is a commonly used model for the analysis of spatial
      point pattern data. Fitting this model is difficult because of its doubly
      stochastic property, i.e., it is an hierarchical combination of a Poisson process
      at the first level and a Gaussian Process at the second level. Various methods
      have been proposed to estimate such a process, including traditional likelihood
      based approaches as well as Bayesian methods. We focus here on Bayesian methods
      and several approaches that have been considered for model fitting within this
      framework, including Hamiltonian Monte Carlo, the Integrated nested Laplace
      approximation, and Variational Bayes. We consider these approaches and make
      comparisons with respect to statistical and computational efficiency. These
      comparisons are made through several simulation studies as well as through two
      applications, the first examining ecological data and the second involving
      neuroimaging data.

PMID- 29200538
TI  - Using Google Scholar institutional level data to evaluate the quality of
      university research.
AB  - In recent years, the extent of formal research evaluation, at all levels from the
      individual to the multiversity has increased dramatically. At the institutional
      level, there are world university rankings based on an ad hoc combination of
      different indicators. There are also national exercises, such as those in the UK
      and Australia that evaluate research outputs and environment through peer review
      panels. These are extremely costly and time consuming. This paper evaluates the
      possibility of using Google Scholar (GS) institutional level data to evaluate
      university research in a relatively automatic way. Several citation-based metrics
      are collected from GS for all 130 UK universities. These are used to evaluate
      performance and produce university rankings which are then compared with various
      rankings based on the 2014 UK Research Excellence Framework (REF). The rankings
      are shown to be credible and to avoid some of the obvious problems of the REF
      ranking, as well as being highly efficient and cost effective. We also
      investigate the possibility of normalizing the results for the university subject
      mix since science subjects generally produce significantly more citations than
      social science or humanities.

PMID- 29200539
TI  - Sequence analysis of annually normalized citation counts: an empirical analysis
      based on the characteristic scores and scales (CSS) method.
AB  - In bibliometrics, only a few publications have focused on the citation histories
      of publications, where the citations for each citing year are assessed. In this
      study, therefore, annual categories of field- and time-normalized citation scores
      (based on the characteristic scores and scales method: 0 = poorly cited, 1 =
      fairly cited, 2 = remarkably cited, and 3 = outstandingly cited) are used to
      study the citation histories of papers. As our dataset, we used all articles
      published in 2000 and their annual citation scores until 2015. We generated
      annual sequences of citation scores (e.g., [Formula: see text]) and compared the
      sequences of annual citation scores of six broader fields (natural sciences,
      engineering and technology, medical and health sciences, agricultural sciences,
      social sciences, and humanities). In agreement with previous studies, our results
      demonstrate that sequences with poorly cited (0) and fairly cited (1) elements
      dominate the publication set; sequences with remarkably cited (3) and
      outstandingly cited (4) periods are rare. The highest percentages of constantly
      poorly cited papers can be found in the social sciences; the lowest percentages
      are in the agricultural sciences and humanities. The largest group of papers with
      remarkably cited (3) and/or outstandingly cited (4) periods shows an increasing
      impact over the citing years with the following orders of sequences: [Formula:
      see text] (6.01%), which is followed by [Formula: see text] (1.62%). Only 0.11%
      of the papers (n = 909) are constantly on the outstandingly cited level.

PMID- 29200540
TI  - A Functional Varying-Coefficient Single-Index Model for Functional Response Data.
AB  - Motivated by the analysis of imaging data, we propose a novel functional varying
      coefficient single index model (FVCSIM) to carry out the regression analysis of
      functional response data on a set of covariates of interest. FVCSIM represents a
      new extension of varying-coefficient single index models for scalar responses
      collected from cross-sectional and longitudinal studies. An efficient estimation
      procedure is developed to iteratively estimate varying coefficient functions,
      link functions, index parameter vectors, and the covariance function of
      individual functions. We systematically examine the asymptotic properties of all
      estimators including the weak convergence of the estimated varying coefficient
      functions, the asymptotic distribution of the estimated index parameter vectors,
      and the uniform convergence rate of the estimated covariance function and their
      spectrum. Simulation studies are carried out to assess the finite-sample
      performance of the proposed procedure. We apply FVCSIM to investigating the
      development of white matter diffusivities along the corpus callosum skeleton
      obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

PMID- 29200541
TI  - The development and validation of the Closed-set Mandarin Sentence (CMS) test.
AB  - Matrix-styled sentence tests offer a closed-set paradigm that may be useful when
      evaluating speech intelligibility. Ideally, sentence test materials should
      reflect the distribution of phonemes within the target language. We developed and
      validated the Closed-set Mandarin Sentence (CMS) test to assess Mandarin speech
      intelligibility in noise. CMS test materials were selected to be familiar words
      and to represent the natural distribution of vowels, consonants, and lexical
      tones found in Mandarin Chinese. Ten key words in each of five categories (Name,
      Verb, Number, Color, and Fruit) were produced by a native Mandarin talker,
      resulting in a total of 50 words that could be combined to produce 100,000 unique
      sentences. Normative data were collected in 10 normal-hearing, adult Mandarin
      speaking Chinese listeners using a closed-set test paradigm. Two test runs were
      conducted for each subject, and 20 sentences per run were randomly generated
      while ensuring that each word was presented only twice in each run. First, the
      level of the words in each category were adjusted to produce equal
      intelligibility in noise. Test-retest reliability for word-in-sentence
      recognition was excellent according to Cronbach's alpha (0.952). After the
      category level adjustments, speech reception thresholds (SRTs) for sentences in
      noise, defined as the signal-to-noise ratio (SNR) that produced 50% correct whole
      sentence recognition, were adaptively measured by adjusting the SNR according to
      the correctness of response. The mean SRT was -7.9 (SE=0.41) and -8.1 (SE=0.34)
      dB for runs 1 and 2, respectively. The mean standard deviation across runs was
      0.93 dB, and paired t-tests showed no significant difference between runs 1 and 2
      (p=0.74) despite random sentences being generated for each run and each subject.
      The results suggest that the CMS provides large stimulus set with which to
      repeatedly and reliably measure Mandarin-speaking listeners' speech understanding
      in noise using a closed-set paradigm.

PMID- 29200542
TI  - A New Variance Component Score Test for Testing Distributed Lag Functions with
      Applications in Time Series Analysis.
AB  - We propose to test a given constrained distributed lag model (DLM) of the form
      beta = Ctheta against an unconstrained alternative using a variance component
      score test (VCST) and show that VCST is more powerful than the standard
      likelihood ratio test in a simulation study.

PMID- 29200543
TI  - A protocol for training group-housed rhesus macaques (Macaca mulatta) to
      cooperate with husbandry and research procedures using positive reinforcement.
AB  - There has been increased recognition of the 3Rs in laboratory animal management
      over the last decade, including improvements in animal handling and housing. For
      example, positive reinforcement is now more widely used to encourage primates to
      cooperate with husbandry procedures, and improved enclosure design allows housing
      in social groups with opportunity to escape and avoid other primates and humans.
      Both practices have become gold standards in captive primate care resulting in
      improved health and behavioural outcomes. However, training individuals and
      social housing may be perceived as incompatible, and so it is important to share
      protocols, their outcomes and suggestions for planning and improvements for
      future uptake. Here we present a protocol with link to video for training rhesus
      macaques (Macaca mulatta) housed in single-male - multi-female breeding groups to
      sit at individual stations in the social enclosure. Our aim was that the monkeys
      could take part in welfare-related cognitive assessments without the need for
      removal from the group or interference by group members. To do this we required
      most individuals in a group to sit by individual stations at the same time. Most
      of the training was conducted by a single trainer with occasional assistance from
      a second trainer depending on availability. We successfully trained 61/65 monkeys
      housed in groups of up to nine adults (plus infants and juveniles) to sit by
      their individual stationing tools for >30 s. Males successfully trained on
      average within 30 min (2 training sessions); females trained on average in 1 h 52
      min +/- 13min (7.44 sessions), with rank (high, mid, low) affecting the number of
      sessions required. On average, dominant females trained in 1 h 26 min +/- 16 min
      (5.7 sessions), mid ranked females in 1 h 52 min +/- 20min (7.45 sessions), and
      subordinate females took 2 h 44 min +/- 36 min (10.9 sessions). Age, group size,
      reproductive status, temperament, and early maternal separation did not influence
      the number of sessions a monkey required to reach criterion. We hope this
      protocol will be useful for facilities worldwide looking to house their animals
      in naturalistic social groups without impacting on animal husbandry and
      management.

PMID- 29200544
TI  - Phoretic motion of soft vesicles and droplets: an XFEM/particle-based numerical
      solution.
AB  - When immersed in solution, surface-active particles interact with solute
      molecules and migrate along gradients of solute concentration. Depending on the
      conditions, this phenomenon could arise from either diffusiophoresis or the
      Marangoni effect, both of which involve strong interactions between the fluid and
      the particle surface. We introduce here a numerical approach that can accurately
      capture these interactions, and thus provide an efficient tool to understand and
      characterize the phoresis of soft particles. The model is based on a combination
      of the extended finite element-that enable the consideration of various
      discontinuities across the particle surface-and the particle-based moving
      interface method-that is used to measure and update the interface deformation in
      time. In addition to validating the approach with analytical solutions, the model
      is used to study the motion of deformable vesicles in solutions with spatial
      variations in both solute concentration and temperature.

PMID- 29200545
TI  - Self-interest may not be entirely in the interest of the self: Association
      between selflessness, dispositional mindfulness and psychological well-being.
AB  - The association between mindfulness and selflessness is firmly grounded in
      classical Indo-Sino-Tibetan contemplative traditions, but has received limited
      empirical attention from Western researchers. In Buddhism, the relationship
      between mindfulness and the self is of central concern to the cultivation of well
      being. Mindfulness is believed to encourage insight into the truly insubstantial
      nature of the self, an understanding that is thought to encourage well-being. The
      present study explores these relationships, attending to dispositional
      mindfulness, the self as it exists on a continuum from self-centered to selfless,
      and psychological well-being. Results indicate a positive relationship between
      selflessness, dispositional mindfulness, and psychological well-being. It appears
      that construing the self as interdependent and interconnected with a broader
      social, natural, and cosmic context is linked with greater psychological well
      being and dispositional mindfulness. Path analyses revealed that selflessness
      mediated the relationship between dispositional mindfulness and psychological
      well-being.

PMID- 29200546
TI  - Post-Disaster Fertility: Hurricane Katrina and the Changing Racial Composition of
      New Orleans.
AB  - Large-scale climate events can have enduring effects on population size and
      composition. Natural disasters affect population fertility through multiple
      mechanisms, including displacement, demand for children, and reproductive care
      access. Fertility effects, in turn, influence the size and composition of new
      birth cohorts, extending the reach of climate events across generations. We study
      these processes in New Orleans during the decade spanning Hurricane Katrina. We
      combine census data, ACS data, and vital statistics data to describe fertility in
      New Orleans and seven comparison cities. Following Katrina, displacement
      contributed to a 30% decline in birth cohort size. Black fertility fell, and
      remained 4% below expected values through 2010. By contrast, white fertility
      increased by 5%. The largest share of births now occurs to white women. These
      fertility differences-beyond migration-driven population change-generate
      additional pressure on the renewal of New Orleans as a city in which the black
      population is substantially smaller in the disaster's wake.

PMID- 29200547
TI  - Assessing the environmental context of hand washing among school children in
      Limpopo, South Africa.
AB  - Despite its simplicity and efficacy, the promotion of hand washing for disease
      prevention remains a challenge particularly in resource-limited settings. Here we
      report on a quasi-experimental school-based study that aimed to improve habitual
      hand washing. Significant increases in hand washing occurred following
      improvements in hygiene and sanitation facilities (School A: t=13.86, p=0.0052).
      Smaller increases in hand washing occurred following education (School A: t=2.63;
      p=0.012; School B, no infrastructure improvements: t=1.66, p=0.239). Health
      policy and programming need to pay greater attention to the interplay of the
      structural, social, and individual dimensions of unique contextual environments
      that influence habitual behaviours.

PMID- 29200548
TI  - Mood Stabilisers, but for Lithium, are not stabilizing Moods! Bipolar Disorders:
      Clinical conundrums 2.

PMID- 29200549
TI  - Ethics in Psychiatric Research: Issues and Recommendations.
AB  - Psychiatric research has increased remarkably over recent decades to help in
      understanding the current trends and better therapeutic options for illness. On
      the other hand, there is also a trend toward higher rates of retraction of
      published papers in the recent years. Ethics is required to maintain and increase
      the overall quality and morality of research. Psychiatric research faces several
      unique ethical challenges. Ethical guidelines are very important tool of research
      which safeguards participants; however, there is a dearth of such guidelines in
      India. The present paper aims to review available ethical issues and guidelines
      pertaining to psychiatric research. A search was conducted on Pubmed using search
      terms (e.g., "ethics," "psychiatry," "research"). Relevant studies were selected
      for the review after manual screening of title/abstract. Additional sources were
      referred to using cross references and Google Scholar. Psychiatric research has
      several important ethical issues which are different from other medical
      disciplines. These issues are related to informed consent, confidentiality,
      conflict of interest, therapeutic misconception, placebo related, vulnerability,
      exploitation, operational challenges, among others. The current paper has made
      several recommendations to deal with ethical challenges commonly faced in
      psychiatric research. The ethical guidelines are utmost needed for Indian
      psychiatric research. Specific guidelines are lacking pertaining to psychiatric
      research. The issues and recommendations merit a further discussion and
      consideration.

PMID- 29200550
TI  - "Vaping:" Emergence of a New Paraphernalia.
AB  - As research, has progressed through ages, we have been able to uncover the true
      nature of nicotine addiction. Humankind is now aware of the various ailments that
      it brings with it. As the slogan for a smokeless world for a better world has
      been raised, a new practice called "vaping" has come to the forefront. The use of
      electronic cigarettes (EC) has been on the rise recently. Claims have been made
      over its role for nicotine deaddiction as well as reducing harmful use for
      chronic nicotine abusers. In the current review, we searched the PubMed database
      for available literatures on this practice. We conclude that though EC has the
      potential to work wonders in smoking cessation, the unforeseen adverse effects
      needs to be evaluated first before its large-scale introduction in market through
      solid evidence-based research.

PMID- 29200551
TI  - Efficacy of Transcranial Direct Current Stimulation in the Treatment: Resistant
      Patients who Suffer from Severe Obsessive-compulsive Disorder.
AB  - Background: During the past years, significant efforts have been made to explain
      the biological backgrounds of obsessive-compulsive disorder (OCD). Cortical
      subcortical and neurotransmitter models are used for explaining the symptoms of
      OCD, so our hypothesis is that brain's transcranial direct current stimulation
      (TDCS) can regulate the brain activities of the OCD patients. Thus, based on the
      mentioned issues, this research seeks to investigate the efficacy of TDCS in
      treatment-resistant patients who suffer from severe OCD. Materials and Methods:
      The present study is a clinical trial research which was based on the available
      sampling method, 42 treatment-resistant patients who suffer from severe OCD were
      selected as research's samples (2015-2016). Medical intervention protocol in this
      study is TDCS cathode type that was done in 15 sessions for 3 consecutive weeks
      (each session was conducted for 30 min daily). Yale-Brown Obsessive-Compulsive
      Scale was used for evaluating the efficacy of TDCS method during the 1st, 5th,
      10th, and 15th sessions and it was also used for checking the 1st and 3rd monthly
      follow-up phases. Results: Variance within-group analysis (repeated measure)
      showed that the mean differences in the different stages of evaluation are
      significant (seven stages of evaluation). Conclusion: TDCS can be introduced as
      an appropriate, strong tool for regulating the brain - behavioral systems and it
      can also be introduced as a suitable alternative treatment for treatment
      resistant patients who suffer from severe OCD.

PMID- 29200552
TI  - Self-inflicted Cut Injury as Common Method of Deliberate Self Harm: A
      Retrospective Study from Nepal.
AB  - Context: Deliberate self-injury, a fairly common condition is present across all
      culture. It is defined as intentional, direct injuring of body tissue without
      suicidal intent. We continue to lack a sufficient understanding of this behavior
      in the context of South East Asian region. Aims: This study aims to explore the
      characteristics of self-cutting, and gender differences in homologous group of
      youth applying for foreign employment in Nepal. Settings and Design: Cross
      sectional, single interview method in an out-patient setting. Subjects and
      Methods: The youths applying for foreign employment were screened for self-harm
      attempt using single question. Screen positive individuals were applied with
      inclusion and exclusion criteria. The data were collected in a single interview
      by consultant psychiatrist. Results: Males were more than females and the mean
      age (standard deviation) at the time of act and current presentation were 16.52
      (3.13) and 24.70 (5.54) years, respectively. Various methods were used in self
      inflicting cut, and certain amount of stress was present in the majority of the
      participants. There was no significant difference between male and female in all
      descriptive characteristics except for mean age at the time of presentation.
      Conclusions: The descriptive results from Nepal are keeping with most of the
      published literature. The study is the first one from Nepal, and we expect that
      this will help in laying a good foundation for further studies with stronger
      methodologies.

PMID- 29200553
TI  - Sociodemographic and Clinical Predictors of Response in Manic Episodes: A
      Naturalistic, Prospective, Cohort Study.
AB  - Background: Response to treatment of a manic episode is dependent on several
      sociodemographic and clinical factors as reported by researchers from other
      countries. The prescription of mood stabilizers and/or antipsychotics for manic
      episode depends on these factors. There is a lack of availability of data from
      India on this topic. Hence, this study was planned to identify the predictors of
      pharmacological response. Materials and Methods: Forty-two patients with a
      diagnosis of bipolar affective disorder current episode manic were enrolled and
      assessed for sociodemographic variables and clinical variables such as age of
      onset, family history, comorbidities, index episode, and number of past episodes.
      They were divided into four groups depending on the treatment they were
      receiving, namely, lithium with an antipsychotic (n = 25), lithium with
      divalproex and an antipsychotic (n = 8), divalproex with an antipsychotic (n =
      5), and the miscellaneous group (n = 4). The primary outcome measure was
      improvement in the Young Mania Rating Scale score and secondary outcome measure
      was duration of ward stay. Results: There was a significant improvement in all
      the treatment modalities and it was comparable. There was no significant impact
      of any sociodemographic or clinical variable on treatment outcome except that
      females had significantly better response than males. There was nearly
      significant shorter duration of hospitalization in the lithium and antipsychotics
      groups compared to divalproex group. Conclusion: All treatment modalities are
      equally efficacious in the management of manic episode in short term. However,
      lithium and antipsychotics tend to produce early response than divalproex. Other
      sociodemographic and clinical predictors were not significantly associated with
      response.

PMID- 29200554
TI  - Role Overload, Role Self Distance, Role Stagnation as Determinants of Job
      Satisfaction and Turnover Intention in Banking Sector.
AB  - Purpose: This study examined the relationship of the organizational role stress:
      Role overload, role self-distance, and role stagnation with job satisfaction and
      turnover intention with a sample of banking employees in India. Methodology: In
      this research, we used the RODS scale developed by Prohit and Pareek (2010) for
      measuring occupational role scale. The reliability of the scale came out to be
      0.71. Findings: The majority of employees of all ranks, in both private and
      public sector banks, suffer from high role stress of all types. It was found that
      role overload and role stagnation are inversely associated with banking
      employees' job satisfaction. Private sector bank employees have more role stress
      and more unsatisfied than employees of public sector banks. Employees Turnover
      intention was found to be positively impacted by job satisfaction, contrary to
      many other studies. Possible reasons have been suggested. Job satisfaction was
      found to play a partial mediating role in the relationship between role overload
      and turnover intention with 40% mediation. Further, employees with longer tenure
      (work experience) have less role stress and are more satisfied. Originality: This
      study is unique in the sense there is hardly any study linking role stress to job
      satisfaction and turnover intention, specially in Indian context.

PMID- 29200555
TI  - Erectile Dysfunction: An Underestimated Presentation in Patients with Diabetes
      Mellitus.
AB  - Introduction: Erectile dysfunction (ED) is a common complication of diabetes
      mellitus. ED, like other sexual disorders, is often under-reported and under
      diagnosed, as talking about sex is considered a taboo in our society.
      Methodology: All the male patients with diabetes mellitus (with or without active
      complaints of ED) attending Medicine or Psychiatry OPD of the institute during
      the study period were enrolled in the study. They were investigated for their
      body-mass index (BMI), blood sugar and lipid profile; and were assessed on HAM-D,
      General Health Questionnaire-30, IIEF, sex myth checklist and QOL Instrument for
      Indian Diabetes Patients (QOLID). Result and Discussion: In the present study, a
      total of 138 diabetic patients were assessed, and those with severe ED were found
      to have poor glycemic control, worse lipid profile, higher body mass index, later
      age of onset, and longer duration of untreated diabetes as compared to non-ED
      patients. ED patients also scored higher on depression rating scale, had poorer
      general health and quality of life (QOL). Early attention to ED in diabetic
      patients can improve general health and QOL of the sufferers. Conclusion: DM
      patients with poor glycemic control and advanced age have a higher propensity of
      developing severe ED, which further deteriorates the already compromised health &
      QOL.

PMID- 29200556
TI  - Reactions to Psychiatry Referral in Patients Presenting with Physical Complaints
      to Medical and Surgical Outpatient Services.
AB  - Background: While it is well known that patients with psychiatric illness feel
      stigmatized, little is known about the reactions to a psychiatric referral among
      those who visit general hospital medical and surgical services for their
      complaints. Materials and Methods: This study assessed the sociodemographic
      details, psychiatric diagnosis, somatic symptom severity, and interview-based
      reactions to referral among patients referred to psychiatry services from other
      departments in a general tertiary hospital in North India. Fifty-nine males and
      101 females were assessed over 6 months for this purpose. Results: A majority of
      patients were diagnosed with a psychiatric disorder and had significant somatic
      symptom severity. The themes explored were the decision to accept the referral,
      possibility of the presence of mental illness as signified by a psychiatric
      diagnosis and factors that enabled or impeded psychiatric treatment seeking.
      Conclusions: Results indicate that patients did not empower in decision-making, a
      reluctance to accept the possibility of a psychiatric diagnosis and accept
      medication and had poor knowledge about psychiatry. Referring clinicians and
      psychiatrists should be sensitive to patient perceptions so that better care is
      possible.

PMID- 29200557
TI  - Stressful and Traumatic Experiences among Women with Alcohol Use Disorders in
      India.
AB  - Aim: The aim of the present study was to examine lifetime stressful and traumatic
      experiences among women with alcohol use disorders (AUDs). Methods: The sample
      comprised of two groups: a clinical group of 35 women with a diagnosis of AUD and
      a comparison group of 60 women drawn from the community. After screening out, the
      participants were administered Life Stressor Checklist-Revised. Results: On an
      average, clinical group was exposed to 7.57 (standard deviation [SD] = 4.14)
      stressful events and comparison group was exposed to 4.03 (SD = 2.80) stressful
      events across the lifespan (t = 4.976; P < 0.001). Clinical group reported a high
      number of childhood abuse and interpersonal traumas across lifespan than
      comparison group. The relationship between adverse life experiences and alcohol
      abuse among women was bidirectional. Conclusion: Understanding the nature and
      experiences of trauma in this group has implications for planning gender
      sensitive treatment programs for women seeking help for AUDs in India.

PMID- 29200558
TI  - Development and Preliminary Testing of the Biopsychosocial Prognosis Scale for
      Coronary Artery Bypass Grafting.
AB  - Background: The present study attempted to develop a self-report scale called
      Biopsychosocial Prognosis Scale for Coronary Artery Bypass grafting (BIPROSCAB)
      that measured patients' prognosis in an integrated manner, a month after they had
      undergone coronary artery bypass grafting (CABG). Method: The development and
      preliminary testing of the psychometric properties of BIPROSCAB followed five
      phases involving 450 patients in total. Results: Findings gave rise to a 25-item
      scale which was subjected to an exploratory factor analysis using principal
      component analysis with varimax rotation. A 9-factor structure emerged, and the
      factors were named post-CABG affect state, post-CABG anxiety, post-CABG physical
      pain, discomfort in surgical sites, worry about return to normalcy, discomfort in
      the leg, CABG bio-social by-products, constraints in socializing, and infection
      and interference to routine life. The reliability, validity, and usability of
      BIPROSCAB were also analyzed. Conclusion: BIPROSCAB is a reliable, valid, and
      useful multidimensional self-report scale for measuring and evaluating the impact
      of medical treatment and psychosocial intervention in patients after CABG.

PMID- 29200559
TI  - A Comparative Study of Factors Associated with Relapse in Alcohol Dependence and
      Opioid Dependence.
AB  - Background: Alcohol and opiates are among the most addictive substances posing
      significant public health problems due to the biopsychosocial impact that they
      have on individuals. Research shows that majority of abstinent alcohol and/or
      opioid dependence subjects relapse within 1 year. It has also been estimated that
      26-36 million people worldwide abuse opiates, with exceptionally high-relapse
      rates. The purpose of this study was to compare the sociodemographic factors and
      correlates relapse in alcohol dependence and opioid dependence. Methodology: This
      research uses a cross-sectional comparative study design with a sample size of 60
      drawn from a population of clinically diagnosed patients of alcohol dependence (n
      = 30) or opioid dependence (n = 30) and seeking treatment for relapse. In
      addition to collecting sociodemographic data, other factors such as craving,
      affect, self-efficacy, and expressed emotions were measured using standardized
      instruments including brief substance craving scale, Bradburn affect balance
      scale, drug avoidance and self-efficacy scale and family emotional involvement,
      and conflict scale. The data were statistically analyzed. Results: Disparity in
      sociodemographic factors was seen in both the groups with opioid group being more
      likely to be single, unemployed, belonging to lower socioeconomic status, and
      having a criminal record (P = 0.025). Among factors associated with relapse, the
      opioid group scored significantly higher on craving, perceived criticism (P =
      0.0001), and lower on self-efficacy (P = 0.016). Most common reason cited for
      relapse in both the groups was desire for positive mood. Conclusion: This study
      highlights the role of social determinants in drug dependence and relapse.
      Relapse was found to be a complex multifactorial phenomenon. Despite differences
      in presentation, somewhat similar relapse mechanisms were seen in both groups.

PMID- 29200560
TI  - A Cross-sectional Study to Estimate Cardiovascular Risk Factors in Patients with
      Bipolar Disorder.
AB  - Background: There is increasing recognition of cardiovascular mortality and
      comorbidity in bipolar disorder (BD) in the recent times. Framingham 10 years
      risk of coronary heart disease (CHD) has been a widely accepted as a reliable
      estimate of cardiovascular risk in the general population. A few studies have
      estimated the relative risk of developing CHD in BDs, in India. We attempt to
      present a cross-sectional data from a prospective study to estimate the 10 years
      cardiovascular risk in BD population. Subjects and Methods: A total of 50
      patients with BD aged between 20 and 60 years fulfilling the inclusion and
      exclusion criteria were enrolled into this study. Demographic variables and
      clinical evaluations including smoking history, medical and pharmacologic
      treatment history, physical examination, anthropometric measurements, and
      clinical laboratories for metabolic profiles were assessed. Using the Framingham
      10-year risk questionnaire, the risk for each patient was calculated and compared
      with that of normal healthy control group. Results: The risk of developing a
      future cardiovascular event was 3.26% in BD and 2.02% in controls. We identified
      that a higher age at onset of illness, waist-hip ratio, total cholesterol, and
      unemployment showed a strong positive correlation with future CHD risk whereas
      administration of valproate, lithium for management of BD, higher socioeconomic
      status and educational status, and nonsmokers was associated negatively with the
      future CHD risk. Conclusions: It appears that there is a significant association
      between BD and metabolic factors, CHD, sociodemographic variables, and
      underscores the predictive ability of Framingham risk score in detecting
      cardiovascular diseases.

PMID- 29200561
TI  - Efficacy of Adjunctive Single Session Counseling for Medically Unexplained
      Symptoms: A Randomized Controlled Trial.
AB  - Context: Medically unexplained symptoms (MUS) are often poorly responsive to
      standard treatments. Aim: The aim of the study is to assess short-term efficacy
      of adjunctive single session cognitive behavior therapy (CBT)-based counseling
      for patients with MUS. Setting and Design: Randomized controlled trial at a
      psychosomatic clinic of a tertiary care hospital. Materials and Methods: Patients
      with MUS were randomized to receive either the single session counseling
      (intervention group) (n = 41) or control group which received treatment as usual
      (n = 35). The counseling intervention focused on three areas - cognitive
      reattribution, shifting focus, and guided muscular relaxation and lasted around
      30 min. The two groups were assessed at baseline and after 1 month for change in
      outcome measures. Statistical Analysis Used: Repeated measures analysis of
      variance. P value was adjusted for multiple comparisons using Bonferroni
      correction and set at <0.01 for significance. Results: Both groups did not differ
      on change in the primary outcome measure: Patient Health Questionnaire - 15
      scores (P = 0.055). However, at follow-up, the intervention group showed
      statistically greater reduction in the number of workdays lost (P = 0.005). Trend
      level changes were noted for depressive symptom reduction only in the
      intervention group (P = 0.022). Conclusions: One session CBT-based therapy
      demonstrates potentially important benefits over standard care among Indian
      patients with MUS. Further testing in larger samples with longer follow-up
      periods is therefore recommended.

PMID- 29200562
TI  - Prevalence and Sociodemographic Profile of Lithium-induced Cutaneous Side Effects
      in Bipolar Affective Disorder Patients: A 1-year Prospective Observational Study
      in South India.
AB  - Objectives: Objective in our study is i) To assess the prevalence and
      sociodemographic profile of cutaneous side effects in bipolar affective disorder
      patients (BPAD) on lithium. ii) To assess the course of pre-existing skin
      reactions, when patient is initiated on lithium therapy. Methods: Lithium induced
      cutaneous side effects were assessed at baseline and monthly for 6 months
      followed by every 2 months over a year. Dermatologist opinion obtained to
      diagnose and treat for each patient who developed cutaneous side effects. Data
      were analyzed in percentage. Results: The prevalence of lithium induced cutaneous
      side effects in our study is 38.46%. On analyzing the individual subtype of
      cutaneous lesions, acneiform eruption and hairfall were most common. The
      cutaneous adverse reactions on lithium are more common in early adulthood than in
      the late adulthood and geriatric age group and among the subtypes of skin lesion
      acneiform eruptions are more common among males than in females. On analyzing the
      course of pre-existing lesions, severe alopecia developed with pre-existing
      systemic lupus erythematosis. Conclusion: These novel finding indicate that
      prevalence of lithium induced cutaneous side effects continues to be high. Hence,
      clinician should educate the patients before initiating lithium to improve
      attrition rate.

PMID- 29200563
TI  - Problems of Face Recognition in Patients with Behavioral Variant Frontotemporal
      Dementia.
AB  - Introduction: Faces are very special as they are most essential for social
      cognition in humans. It is partly understood that face processing in its
      abstractness involves several extra striate areas. One of the most important
      causes for caregiver suffering in patients with anterior dementia is lack of
      empathy. This apart from being a behavioral disorder could be also due to failure
      to categorize the emotions of the people around them. Patients and Methods:
      Inlusion criteria: DSM IV for Bv FTD Tested for prosopagnosia - familiar faces,
      famous face, smiling face, crying face and reflected face using a simple picture
      card (figure 1). Exclusion Criteria: Advanced illness and mixed causes.
      Observations: 46 patients (15 females, 31 males) 24 had defective face
      recognition. (mean age 51.5),10/15 females (70%) and 14/31males(47. Familiar face
      recognition defect was found in 6/10 females and 6/14 males. Total- 40%(6/15)
      females and 19.35%(6/31)males with FTD had familiar face recognition. Famous
      Face: 9/10 females and 7/14 males. Total- 60% (9/15) females with FTD had famous
      face recognition defect as against 22.6%(7/31) males with FTD Smiling face
      defects in 8/10 female and no males. Total- 53.33% (8/15) females. Crying face
      recognition defect in 3/10 female and 2 /14 males. Total- 20%(3/15) females and
      6.5%(2/31) males. Reflected face recognition defect in 4 females. Results: Famous
      face recognition and positive emotion recognition defect in 80%, only 20%
      comprehend positive emotions, Face recognition defects are found in only 45% of
      males and more common in females. Conclusion: Face recognition is more affected
      in females with FTD There is differential involvement of different aspects of the
      face recognition could be one of the important factor underlying decline in the
      emotional and social behavior of these patients. Understanding these pathological
      processes will give more insight regarding patient behavior.

PMID- 29200564
TI  - Family Loading and Morbidity Risk of Attention-deficit Hyperactivity Disorder in
      Patients with Alcohol-dependence Syndrome.
AB  - Background: Attention-deficit hyperactivity disorder (ADHD) and substance-use
      disorders often co-occur. Aim: Aim of this study was to look at the family
      loading of ADHD (in adults and children) in patients with alcohol-dependence
      syndrome (ADS) along with the estimation of morbidity risk (MR) for developing
      ADHD. Methods: Thirty-five male patients with ADS along with their 369 first
      degree relatives (FDRs) - both children and adults - were recruited. Results:
      ADHD and residual ADD (ADDRT) were significantly more common in the early-onset
      (EO) ADS group and their FDR. In ADHD children, high MR (27.27%) for developing
      EO of ADS was noted. Discussion: Findings from this study raise an avenue for
      research in the Indian population about the shared risk between ADS and ADHD.

PMID- 29200565
TI  - Can We Call It "Stinky-finger Syndrome?"
AB  - Many accounts refer to insertion of finger into anus mostly for gratification
      from stimulation of prostate gland, but index case Mr. M. continued doing this to
      get rid of constipation that eventually led to feelings of guilt, stinky fingers,
      not able to defecate normally, and dysphoric emotions. Further research is needed
      to find out the phenomenology of this condition.

PMID- 29200566
TI  - Opioid Withdrawal Presenting as Delirium and Role of Buprenorphine: A Case
      Series.
AB  - Opioid withdrawal is very rarely characterized by delirium unlike alcohol or
      benzodiazepine withdrawal. PubMed search through October 2016 reveals only two
      case series on delirium as feature of withdrawal in opioid dependence syndrome.
      We report two cases of opioid withdrawal (heroin) presenting with delirium when
      low-dose buprenorphine (2 mg/day) was added. Both the cases had no other
      substance abuse history and nil contributory past and family history. Both of
      them were improved after increasing the buprenorphine dosage to 6-8 mg/day. The
      possibility of delirium as a part of withdrawal symptom or as a phenomenon
      induced by buprenorphine or due to impurities in the heroin used is discussed.

PMID- 29200567
TI  - The Menacing Side of Valproate: A Case Series of Valproate-induced
      Hyperammonemia.
AB  - Valproate (VPA) is a well-tolerated and commonly used drug to treat variety of
      psychiatric and neurological disorders. VPA-induced hyperammonemic encephalopathy
      is a rare adverse effect which can commonly occur in the background of normal
      liver function and therapeutic serum levels. Any delay in treatment of VPA
      induced hyperammonemic encephalopathy can lead to life-threatening coma thus a
      strong clinical suspicion, fair understanding of the pathophysiology, and
      management of this drug-related complication can prevent fatal outcome. We hereby
      report a series of cases admitted to a tertiary care center that developed
      hyperammonemia and all patients recovered on stopping VPA. This case series
      cautions the clinicians about hyperammonemia as an uncommon but highly plausible
      life-threatening side effect, emphasizing astute observation, and high degree of
      clinical suspicion to prevent mortality and limit morbidity. Early recognition of
      subtle gastrointestinal, cognitive, and behavioral signs can lead to immediate
      intervention with satisfying results.

PMID- 29200568
TI  - A Serial Munchausen Syndrome by Proxy.
AB  - Munchausen syndrome by proxy (MSBP) is a form of child abuse that describes
      children whose parents or caregivers invent illness stories and substantiate the
      stories by fabricating false physical signs. Through this case report, a serial
      MSBP case is presented along with psychiatric evaluation of the perpetrator
      mother who was sent to the Forensic Psychiatric Observation Department of the
      Council of Forensic Medicine to assess whether she has any mental disorder.
      Although there are several studies on MSBP, we present this case because the
      perpetrator mother was caught on the camera surveillance system of the hospital
      while closing the nose and mouth of the victim for fabricating the illness, and
      she also said that she had done the same thing to her two elder children to
      exclude their illnesses. Her two children had died and could not be diagnosed.
      Moreover, we discuss the psychopathology of the perpetrators, which is a less
      known area of MSBP. This is a very serious form of child abuse, with a high risk
      of repetition, and failure to diagnose might result in the death of the child.

PMID- 29200570
TI  - Clozapine-induced Acute Hypertriglyceridemia.
AB  - The aim of this study is to highlight the association between the use of
      clozapine and the early development of hypertriglyceridemia, a condition that
      substantially increases the risk of cardiovascular events and other medical
      complications. A 34-year-old female with a background history of schizophrenia
      presented with acute elevation of serum triglycerides and cholesterol within 2
      weeks of starting clozapine. Her metabolic parameters normalized following
      discontinuation of clozapine. Possible hypotheses for lipid dysregulation with
      atypical antipsychotics include weight gain, dietary changes, and development of
      glucose intolerance; however, some other factors may be responsible for this
      rapid escalation of lipid levels. Lipid and metabolic profiles should be closely
      monitored in patients receiving clozapine to facilitate early detection and
      intervention to prevent further health complications.

PMID- 29200569
TI  - Misidentification of Wilson Disease as Schizophrenia (1998-2013): Case Report and
      Review.
AB  - Wilson's disease (WD) is a neurodegenerative disorder due to copper metabolism.
      Schizophrenia-like psychosis and delusional disorder are rare forms of
      psychiatric manifestations of WD. The lack of recognition of these signs and
      symptoms as being attributable to WD often leads to delays in diagnosis and
      management. Knowledge about relationship of the psychiatric manifestations to WD
      can help with the administration of adequate management aimed at both the
      psychiatric issues and underlying WD. The objectives of this article are to
      review case reports whose subject is the incorrect diagnosis of schizophrenia or
      schizophrenia-like syndrome in patients with WD and to detail one case of this
      mismanagement of the disease. A 35-year-old unmarried Iranian woman presented to
      the consulting psychiatrist in the emergency room after a suicide attempt due to
      commanding auditory hallucination. She had previous eleven admissions in
      psychiatric hospital with major depressive episode with psychotic features,
      schizoaffective disorders, and then schizophrenia diagnosis. Nineteen years after
      her first symptoms, it was discovered that the patient was suffering from WD. We
      searched Google Scholar, Ovid, PsycINFO, CINHAL, and PubMed databases from 1985
      to 2015. Finally, 14 researches were entered into the study. Psychiatric
      manifestations may precede the diagnosis of WD and other symptoms related to
      neurological or hepatic impairment. Early detection of WD is important to prevent
      catastrophic outcome. Young patients presenting with psychiatric presentations
      along with abnormal movement disorder, seizure, or conversion-like symptoms
      should be evaluate for WD even if signs and symptoms are typically suggestive of
      schizophrenia or manic episode. An interdisciplinary approach with good
      collaboration of psychiatrists and neurologists is crucial for WD because early
      diagnosis and management without delay is an important for good prognosis.

PMID- 29200571
TI  - Adolescent-onset X-linked Adrenoleukodystrophy Presenting as Treatment-resistant
      Bipolar Disorder.
AB  - A small proportion of bipolar disorder of adolescent onset can be secondary to
      underlying neurological disorder (secondary mania). We report a case of treatment
      resistant mania secondary to cerebral form of adrenoleukodystrophy of adolescent
      onset. This case demonstrates the need for clinicians to be alert to the
      possibility of rare neurological diseases that can present with psychiatric
      manifestations.

PMID- 29200572
TI  - A Case of Carbamazepine-induced Severe Cholestatic Hepatitis: Case Report and
      Review of Literature.
AB  - Carbamazepine (CBZ) is one of the widely prescribed drugs in the field of
      neuropsychiatry. We report a case of a 27-year-old female patient presenting with
      severe cholestatic hepatitis presenting after the initiation of CBZ. We establish
      the probability of drug-induced liver injury using Council for International
      Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method
      causality assessment scale, and the patient had high probability with a score of
      9. We briefly review the literature in this field discussing the scope of the
      problem, etiopathogenesis, clinical manifestation, course, and management.

PMID- 29200573
TI  - Neural Effects of Transcranial Direct Current Stimulation in Schizophrenia: A
      Case Study using Functional Near-infrared Spectroscopy.
AB  - Schizophrenia is a severe neuropsychiatric disorder characterized by delusions,
      hallucinations, behavioral symptoms, and cognitive deficits. Roughly, 70%-80% of
      schizophrenia patients experience auditory verbal hallucinations (AVHs), with 25%
      30% demonstrating resistance to conventional antipsychotic medications. Studies
      suggest a promising role for add-on transcranial direct current stimulation
      (tDCS) in the treatment of medication-refractory AVHs. The mechanisms through
      which tDCS could be therapeutic in such cases are unclear, but possibly involve
      neuroplastic effects. In recent years, functional near-infrared spectroscopy
      (fNIRS) has been used successfully to study tDCS-induced neuroplastic changes. In
      a double-blind, sham-controlled design, we applied fNIRS to measure task
      dependent cerebral blood flow (CBF) changes as a surrogate outcome of single
      session tDCS-induced effects on neuroplasticity in a schizophrenia patient with
      persistent auditory hallucinations. The observations are discussed in this case
      report.

PMID- 29200574
TI  - Baclofen Overdose Presenting as Psychosis with Catatonia.
AB  - Baclofen is a centrally acting gamma-aminobutyric acid receptor agonist with many
      therapeutic uses in neurology and psychiatry. An overdose of baclofen is known to
      cause serious side effects such as encephalopathy, seizures, respiratory
      depression, and delirium. Association of baclofen with psychosis has also been
      reported. In this case report, we are highlighting the manifestation of catatonic
      features in addition to psychosis following baclofen overdose.

PMID- 29200575
TI  - Are we Overdiagnosing Bipolar Disorder?
AB  - Bipolar disorder (BD) is an established diagnostic entity used by clinicians for
      over a century. It is distinguished by the distinct manic and depressive episodes
      with interepisode euthymia. It has an illness course where both recovery and
      recurrences are a rule and has a good long-term prognosis, as reported earlier by
      Emil Kraeplin. There is an opinion in the current literature that BD is often
      underdiagnosed as unipolar depression, and based on that opinion, spectrum
      concept was introduced. Here, we present 5 cases to highlight that overdiagnosis
      of BD is also not infrequent and we discuss its reasons and therapeutic
      implications.

PMID- 29200576
TI  - Digital Platforms for Mental Health-care Delivery.
AB  - Mental, neurological, and substance abuse disorders cause huge burden. The
      available resources to tackle the huge burden are insufficient, inequitably
      distributed, and inefficiently used, which results in a large majority of people
      with these disorders receiving no care at all. Advances in technology can be used
      to address the concerns. At present, technology is utilized in online
      psychological interventions and mobile apps in the United States of America and
      United Kingdom. In India, technological advances are utilized in telemental
      health, mobile apps, software aiding psychological assessment and retraining,
      training for mental health professionals, and information delivery to general
      public. Although this would be cost effective, digital divide, ethical and legal
      issues have to be addressed for better penetration of the health technologies to
      the persons in need.

PMID- 29200577
TI  - Unguided Mental Health Self-help Apps: Reflections on Challenges through a
      Clinician's Lens.
AB  - The past one decade has witnessed a boom in the availability of Internet-based
      self-help apps in the field of mental health. Several apps have emerged that aim
      to provide information and strategies to empower individuals with self-help
      approaches to deal with issues and concerns related to mental health. A large
      number of these apps in developing countries are likely to be those which depend
      entirely on the users to go over the self-help program on their own (unguided
      internet-based self-help). Only a few apps add a component of periodic
      professional contact/technical support through phone/email or other means to
      supplement the self-help strategies suggested in the app that the user is
      expected to utilize. This scenario poses several challenges in use of unguided
      self-help apps for mental health. This paper enumerates some of these challenges
      for potential users of the apps from the perspective of clinicians. These range
      from difficulties in choosing the right app, limited scope for contextualization,
      and motivation management to awareness about when to step up to a higher
      intensity intervention. Despite these challenges, unguided self-help apps can
      serve important purposes, and hence we propose a few recommendations to address
      such challenges.

PMID- 29200578
TI  - Gender Differences in the 5 Years Course of Bipolar Disorder after a First Manic
      Episode: A Retrospective Review.

PMID- 29200579
TI  - Biomarkers in autism spectrum disorders: An illusion or promising reality?

PMID- 29200580
TI  - Disability Certification in India: Indian Disability Evaluation and Assessment
      Scale versus World Health Organization Disability Assessment Schedule.

PMID- 29200581
TI  - Cholesterol and Mental Health: A Balanced Perspective.

PMID- 29200582
TI  - The "EMIC" and "ETIC" Models: Two Equally Important Insight Assessments in
      Psychosis.

PMID- 29200583
TI  - Lurasidone-induced Oculogyric Crisis.

PMID- 29200584
TI  - The multi-stripe travelling salesman problem.
AB  - In the classical Travelling Salesman Problem (TSP), the objective function sums
      the costs for travelling from one city to the next city along the tour. In the q
      stripe TSP with [Formula: see text], the objective function sums the costs for
      travelling from one city to each of the next q cities in the tour. The resulting
      q-stripe TSP generalizes the TSP and forms a special case of the quadratic
      assignment problem. We analyze the computational complexity of the q-stripe TSP
      for various classes of specially structured distance matrices. We derive NP
      hardness results as well as polynomially solvable cases. One of our main results
      generalizes a well-known theorem of Kalmanson from the classical TSP to the q
      stripe TSP.

PMID- 29200585
TI  - Surface hydrophobicity and acidity effect on alumina catalyst in catalytic
      methanol dehydration reaction.
AB  - BACKGROUND: Methanol to dimethyl ether (MTD) is considered one of the main routes
      for the production of clean bio-fuel. The effect of copper loading on the
      catalytic performance of different phases of alumina that formed by calcination
      at two different temperatures was examined for the dehydration of methanol to
      dimethyl ether (DME). RESULTS: A range of Cu loadings of (1, 2, 4, 6, 10 and 15%
      Cu wt/wt) on Al2O3 calcined at 350 and 550  degrees C were prepared and
      characterized by TGA, XRD, BET, NH3-TPD, TEM, H2-TPR, SEM, EDX, XPS and DRIFT
      Pyridine techniques. The prepared catalysts were used in a fixed bed reactor
      under reaction conditions in which the temperature ranged from 180-300  degrees C
      with weight hourly space velocity (WHSV) = 12.1 h-1. It was observed that all
      catalysts calcined at 550  degrees C (gamma-Al2O3 support phase) exhibited higher
      activity than those calcined at 350  degrees C (gamma-AlOOH), and this is due to
      the phase support change. Furthermore, the optimum Cu loading was found to be 6%
      Cu/gamma-Al2O3 with this catalyst also showing a high degree of stability under
      steady state conditions and this is attributed to the enhancement in surface
      acidity and hydrophobicity. CONCLUSION: The addition of copper to the support
      improved the catalyst properties and activity. For all the copper modified
      catalysts, the optimum catalyst with high degree of activity and stability was 6%
      copper loaded on gamma alumina. (c) 2017 The Authors. Journal of Chemical
      Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of
      Society of Chemical Industry.

PMID- 29200586
TI  - Gas diffusion electrodes improve hydrogen gas mass transfer for a hydrogen
      oxidizing bioanode.
AB  - Background: Bioelectrochemical systems (BESs) are capable of recovery of metals
      at a cathode through oxidation of organic substrate at an anode. Recently, also
      hydrogen gas was used as an electron donor for recovery of copper in BESs.
      Oxidation of hydrogen gas produced a current density of 0.8 A m-2 and combined
      with Cu2+ reduction at the cathode, produced 0.25 W m-2. The main factor limiting
      current production was the mass transfer of hydrogen to the biofilm due to the
      low solubility of hydrogen in the anolyte. Here, the mass transfer of hydrogen
      gas to the bioanode was improved by use of a gas diffusion electrode (GDE).
      Results: With the GDE, hydrogen was oxidized to produce a current density of 2.9
      A m-2 at an anode potential of -0.2 V. Addition of bicarbonate to the influent
      led to production of acetate, in addition to current. At a bicarbonate
      concentration of 50 mmol L-1, current density increased to 10.7 A m-2 at an anode
      potential of -0.2 V. This increase in current density could be due to oxidation
      of formed acetate in addition to oxidation of hydrogen, or enhanced growth of
      hydrogen oxidizing bacteria due to the availability of acetate as carbon source.
      The effect of mass transfer was further assessed through enhanced mixing and in
      combination with the addition of bicarbonate (50 mmol L-1) current density
      increased further to 17.1 A m-2. Conclusion: Hydrogen gas may offer opportunities
      as electron donor for bioanodes, with acetate as potential intermediate, at
      locations where excess hydrogen and no organics are available. (c) 2017 The
      Authors. Journal of Chemical Technology & Biotechnology published by John Wiley &
      Sons Ltd on behalf of Society of Chemical Industry.

PMID- 29200587
TI  - Impact of Teacher Value Orientations on Student Learning in Physical Education.
AB  - Based on the value orientation theory, the purpose of this study was to determine
      the impact of value orientation incongruence between physical education teachers
      and an externally designed curriculum on student learning in a concept-based
      fitness-centered physical education curriculum. Physical education teachers (n =
      15) with different value orientations taught an externally designed, standards
      based fitness/healthful living curriculum to their middle school students (n =
      3,827) in 155 sixth, seventh, and eighth grade intact classes. A pre-post
      assessment design was used to determine whether student fitness/healthful living
      knowledge gains differed in terms of teachers' value orientations. An ANOVA on
      class means of residual-adjusted knowledge gain scores revealed no statistically
      significant differences based on value orientations. The evidence suggests that
      teacher value orientation impact may be mediated by curriculum impact. This
      finding supports the observation that a well-designed physical education
      curriculum may minimize the impact of teachers' diverse value orientations on the
      curriculum implementation and student learning.

PMID- 29200588
TI  - Characterizing healthy and osteoarthritic knee cartilage on phase contrast CT
      with geometric texture features.
AB  - The current approach to evaluating cartilage degeneration at the knee joint
      requires visualization of the joint space on radiographic images where indirect
      cues such as joint space narrowing serve as markers for osteoarthritis. A recent
      novel approach to visualizing the knee cartilage matrix using phase contrast
      imaging (PCI) with computed tomography (CT) was shown to allow direct examination
      of chondrocyte patterns and their subsequent correlation to osteoarthritis. This
      study aims to characterize chondrocyte cell patterns in the radial zone of the
      knee cartilage matrix in the presence and absence of osteoarthritic damage
      through texture analysis. Statistical features derived from gray-level co
      occurrence matrices (GLCM) and geometric features derived from the Scaling Index
      Method (SIM) were extracted from 404 regions of interest (ROI) annotated on PCI
      images of healthy and osteoarthritic specimens of knee cartilage. These texture
      features were then used in a machine learning task to classify ROIs as healthy or
      osteoarthritic. A fuzzy k-nearest neighbor classifier was used and its
      performance was evaluated using the area under the Receiver Operating
      Characteristic (ROC) curve (AUC). The best classification performance was
      observed with high-dimensional geometrical feature vectors derived from SIM and
      GLCM correlation features. With the experimental conditions used in this study,
      both SIM and GLCM achieved a high classification performance (AUC value of 0.98)
      in the task of distinguishing between healthy and osteoarthritic ROIs. These
      results show that such quantitative analysis of chondrocyte patterns in the knee
      cartilage matrix can distinguish between healthy and osteoarthritic tissue with
      high accuracy.

PMID- 29200589
TI  - The effect of elastic modulus on ablation catheter contact area.
AB  - Cardiac ablation consists of navigating a catheter into the heart and delivering
      RF energy to electrically isolate tissue regions that generate or propagate
      arrhythmia. Besides the challenges of accurate and precise targeting of the
      arrhythmic sites within the beating heart, limited information is currently
      available to the cardiologist regarding intricate electrode-tissue contact, which
      directly impacts the quality of produced lesions. Recent advances in ablation
      catheter design provide intra-procedural estimates of tissue-catheter contact
      force, but the most direct indicator of lesion quality for any particular energy
      level and duration is the tissue-catheter contact area, and that is a function of
      not only force, but catheter pose and material elasticity as well. In this
      experiment, we have employed real-time ultrasound (US) imaging to determine the
      complete interaction between the ablation electrode and tissue to accurately
      estimate contact, which will help to better understand the effect of catheter
      pose and position relative to the tissue. By simultaneously recording tracked
      position, force reading and US image of the ablation catheter, the differing
      material properties of polyvinyl alcohol cryogel[1] phantoms are shown to produce
      varying amounts of tissue depression and contact area (implying varying lesion
      quality) for equivalent force readings. We have shown that the elastic modulus
      significantly affects the surface-contact area between the catheter and tissue at
      any level of contact force. Thus we provide evidence that a prescribed level of
      catheter force may not always provide sufficient contact area to produce an
      effective ablation lesion in the prescribed ablation time.

PMID- 29200590
TI  - Characterizing Trabecular Bone structure for Assessing Vertebral Fracture Risk on
      Volumetric Quantitative Computed Tomography.
AB  - While the proximal femur is preferred for measuring bone mineral density (BMD) in
      fracture risk estimation, the introduction of volumetric quantitative computed
      tomography has revealed stronger associations between BMD and spinal fracture
      status. In this study, we propose to capture properties of trabecular bone
      structure in spinal vertebrae with advanced second-order statistical features for
      purposes of fracture risk assessment. For this purpose, axial multi-detector CT
      (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body
      256-row CT scanner with a dedicated calibration phantom. A semi-automated method
      was used to annotate the trabecular compartment in the central vertebral slice
      with a circular region of interest (ROI) to exclude cortical bone; pixels within
      were converted to values indicative of BMD. Six second-order statistical features
      derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the
      ROI were then extracted and used in conjunction with a generalized radial basis
      functions (GRBF) neural network to predict the failure load of the specimens;
      true failure load was measured through biomechanical testing. Prediction
      performance was evaluated with a root-mean-square error (RMSE) metric. The best
      prediction performance was observed with GLCM feature 'correlation' (RMSE = 1.02
      +/- 0.18), which significantly outperformed all other GLCM features (p < 0.01).
      GLCM feature correlation also significantly outperformed MDCT-measured mean BMD
      (RMSE = 1.11 +/- 0.17) (p < 10-4). These results suggest that biomechanical
      strength prediction in spinal vertebrae can be significantly improved through
      characterization of trabecular bone structure with GLCM-derived texture features.

PMID- 29200591
TI  - Investigating the use of mutual information and non-metric clustering for
      functional connectivity analysis on resting-state functional MRI.
AB  - Functional MRI (fMRI) is currently used to investigate structural and functional
      connectivity in human brain networks. To this end, previous studies have proposed
      computational methods that involve assumptions that can induce information loss,
      such as assumed linear coupling of the fMRI signals or requiring dimension
      reduction. This study presents a new computational framework for investigating
      the functional connectivity in the brain and recovering network structure while
      reducing the information loss inherent in previous methods. For this purpose,
      pair-wise mutual information (MI) was extracted from all pixel time series within
      the brain on resting-state fMRI data. Non-metric topographic mapping of proximity
      (TMP) data was subsequently applied to recover network structure from the pair
      wise MI analysis. Our computational framework is demonstrated in the task of
      identifying regions of the primary motor cortex network on resting state fMRI
      data. For ground truth comparison, we also localized regions of the primary motor
      cortex associated with hand movement in a task-based fMRI sequence with a finger
      tapping stimulus function. The similarity between our pair-wise MI clustering
      results and the ground truth is evaluated using the dice coefficient. Our results
      show that non-metric clustering with the TMP algorithm, as performed on pair-wise
      MI analysis, was able to detect the primary motor cortex network and achieved a
      dice coefficient of 0.53 in terms of overlap with the ground truth. Thus, we
      conclude that our computational framework can extract and visualize valuable
      information concerning the underlying network structure between different regions
      of the brain in resting state fMRI.

PMID- 29200592
TI  - Reduction of Beam Hardening Artifacts in Cone-Beam CT Imaging via SMART-RECON
      Algorithm.
AB  - When an automatic exposure control is introduced in C-arm cone beam CT data
      acquisition, the spectral inconsistencies between acquired projection data are
      exacerbated. As a result, conventional water/bone correction schemes are not as
      effective as in conventional diagnostic x-ray CT acquisitions with a fixed tube
      potential. In this paper, a new method was proposed to reconstruct several images
      with different degrees of spectral consistency and thus different levels of beam
      hardening artifacts. The new method relies neither on prior knowledge of the x
      ray beam spectrum nor on prior compositional information of the imaging object.
      Numerical simulations were used to validate the algorithm.

PMID- 29200593
TI  - Noise characteristics of CT perfusion imaging: How does noise propagate from
      source images to final perfusion maps?
AB  - Cerebral CT perfusion (CTP) imaging is playing an important role in the diagnosis
      and treatment of acute ischemic strokes. Meanwhile, the reliability of CTP-based
      ischemic lesion detection has been challenged due to the noisy appearance and low
      signal-to-noise ratio of CTP maps. To reduce noise and improve image quality, a
      rigorous study on the noise transfer properties of CTP systems is highly
      desirable to provide the needed scientific guidance. This paper concerns how
      noise in the CTP source images propagates to the final CTP maps. Both theoretical
      deviations and subsequent validation experiments demonstrated that, the noise
      level of background frames plays a dominant role in the noise of the cerebral
      blood volume (CBV) maps. This is in direct contradiction with the general belief
      that noise of non-background image frames is of greater importance in CTP
      imaging. The study found that when radiation doses delivered to the background
      frames and to all non-background frames are equal, lowest noise variance is
      achieved in the final CBV maps. This novel equality condition provides a
      practical means to optimize radiation dose delivery in CTP data acquisition:
      radiation exposures should be modulated between background frames and non
      background frames so that the above equality condition is satisinAed. For several
      typical CTP acquisition protocols, numerical simulations and in vivo canine
      experiment demonstrated that noise of CBV can be effectively reduced using the
      proposed exposure modulation method.

PMID- 29200594
TI  - Mask free Intravenous 3D Digital Subtraction Angiography (IV 3D-DSA) from a
      single C-arm acquisition.
AB  - Currently, clinical acquisition of IV 3D-DSA requires two separate scans: one
      mask scan without contrast medium and a filled scan with contrast injection.
      Having two separate scans adds radiation dose to the patient and increases the
      likelihood of suffering inadvertent patient motion induced mis-registration and
      the associated mis-registraion artifacts in IV 3D-DSA images. In this paper, a
      new technique, SMART-RECON is introduced to generate IV 3D-DSA images from a
      single Cone Beam CT (CBCT) acquisition to eliminate the mask scan. Potential
      benefits of eliminating mask scan would be: (1) both radiation dose and scan time
      can be reduced by a factor of 2; (2) intra-sweep motion can be eliminated; (3)
      inter-sweep motion can be mitigated. Numerical simulations were used to validate
      the algorithm in terms of contrast recoverability and the ability to mitigate
      limited view artifacts.

PMID- 29200595
TI  - Increasing Safety of a Robotic System for Inner Ear Surgery Using Probabilistic
      Error Modeling Near Vital Anatomy.
AB  - Safe and effective planning for robotic surgery that involves cutting or ablation
      of tissue must consider all potential sources of error when determining how close
      the tool may come to vital anatomy. A pre-operative plan that does not adequately
      consider potential deviations from ideal system behavior may lead to patient
      injury. Conversely, a plan that is overly conservative may result in ineffective
      or incomplete performance of the task. Thus, enforcing simple, uniform-thickness
      safety margins around vital anatomy is insufficient in the presence of spatially
      varying, anisotropic error. Prior work has used registration error to determine a
      variable-thickness safety margin around vital structures that must be approached
      during mastoidectomy but ultimately preserved. In this paper, these methods are
      extended to incorporate image distortion and physical robot errors, including
      kinematic errors and deflections of the robot. These additional sources of error
      are discussed and stochastic models for a bone-attached robot for otologic
      surgery are developed. An algorithm for generating appropriate safety margins
      based on a desired probability of preserving the underlying anatomical structure
      is presented. Simulations are performed on a CT scan of a cadaver head and safety
      margins are calculated around several critical structures for planning of a
      robotic mastoidectomy.

PMID- 29200596
TI  - Detecting Altered connectivity patterns in HIV associated neurocognitive
      impairment using Mutual Connectivity Analysis.
AB  - The use of functional Magnetic Resonance Imaging (fMRI) has provided interesting
      insights into our understanding of the brain. In clinical setups these scans have
      been used to detect and study changes in the brain network properties in various
      neurological disorders. A large percentage of subjects infected with HIV present
      cognitive deficits, which are known as HIV associated neurocognitive disorder
      (HAND). In this study we propose to use our novel technique named Mutual
      Connectivity Analysis (MCA) to detect differences in brain networks in subjects
      with and without HIV infection. Resting state functional MRI scans acquired from
      10 subjects (5 HIV+ and 5 HIV-) were subject to standard pre-processing routines.
      Subsequently, the average time-series for each brain region of the Automated
      Anatomic Labeling (AAL) atlas are extracted and used with the MCA framework to
      obtain a graph characterizing the interactions between them. The network graphs
      obtained for different subjects are then compared using Network-Based Statistics
      (NBS), which is an approach to detect differences between graphs edges while
      controlling for the family-wise error rate when mass univariate testing is
      performed. Applying this approach on the graphs obtained yields a single network
      encompassing 42 nodes and 65 edges, which is significantly different between the
      two subject groups. Specifically connections to the regions in and around the
      basal ganglia are significantly decreased. Also some nodes corresponding to the
      posterior cingulate cortex are affected. These results are inline with our
      current understanding of pathophysiological mechanisms of HIV associated
      neurocognitive disease (HAND) and other HIV based fMRI connectivity studies.
      Hence, we illustrate the applicability of our novel approach with network-based
      statistics in a clinical case-control study to detect differences connectivity
      patterns.

PMID- 29200597
TI  - Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related
      Diseases in the Han Population.
AB  - Fibulin-3 has been reported as a potential biomarker for mesothelioma. However,
      little is known about the diagnostic efficacies of fibulin-3 for asbestos-related
      diseases (ARDs) in China. This study was to investigate the utility of fibulin-3
      for asbestos exposure and ARDs. A total of 430 subjects were recruited from
      Southeast China, including healthy individuals, asbestos-exposed (AE)
      individuals, and patients with pleural plaques (PP), asbestosis, and malignant
      pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked
      immunosorbent assay. Linear regression analyses were applied to explore the
      influencing factors of fibulin-3. Receiver operating characteristic curves were
      used to determine the cutoff values. The median fibulin-3 level of subjects in
      the mesothelioma group was higher than that in other groups. Subjects in the
      asbestosis group had higher median fibulin-3 level than those in the control
      group. A higher fibulin-3 level was found in the group with >=10 years of
      asbestos exposure as compared with control groups. The AUCs of fibulin-3 for
      distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were
      0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that
      fibulin-3 could be a potential biomarker for the early screening of MPM, but not
      of other nonmalignant ARDs in Chinese populations.

PMID- 29200598
TI  - Vitamin D Status, Disease Activity, and Endothelial Dysfunction in Early
      Rheumatoid Arthritis Patients.
AB  - Cardiovascular diseases represent important complications in rheumatoid arthritis
      (RA) patients, generated by an accelerated atherosclerosis. The aim of this study
      is represented by the assessment of the correlations between serum levels of
      vitamin D, disease activity, and endothelial dysfunction in patients with early
      RA. Material and Methods. The study was performed on a group of 35 patients with
      early RA and 35 healthy subjects matched for age and gender, as controls. In all
      studied subjects, the following were determined: inflammatory markers, insulin
      resistance, vitamin D levels, and endothelial dysfunction. Statistical analysis
      were performed using the Student's t-test and the Pearson's test. p values of
      less than 0.05 were considered statistically significant. Results. The group of
      patients with RA patients presented inflammation, low levels of vitamin D,
      elevated insulin resistance, and reduced flow-mediated vasodilation,
      statistically significant compared to the control group (p < 0.00001).
      Significant inverse correlations between the levels of 25(OH) vitamin D and
      DAS28, respective insulin resistance, and significant positive correlation
      between 25(OH) vitamin D and endothelial function were demonstrated. Conclusion.
      In early RA patients with moderate and high disease activity, low serum levels of
      vitamin D were associated with disease activity, increased insulin resistance,
      and endothelial dysfunction.

PMID- 29200600
TI  - Simultaneous treatment of unspecified heteroskedastic model error distribution
      and mismeasured covariates for restricted moment models.
AB  - We develop consistent and efficient estimation of parameters in general
      regression models with mismeasured covariates. We assume the model error and
      covariate distributions are unspecified, and the measurement error distribution
      is a general parametric distribution with unknown variance-covariance. We
      construct root-n consistent, asymptotically normal and locally efficient
      estimators using the semiparametric efficient score. We do not estimate any
      unknown distribution or model error heteroskedasticity. Instead, we form the
      estimator under possibly incorrect working distribution models for the model
      error, error-prone covariate, or both. Empirical results demonstrate robustness
      to different incorrect working models in homoscedastic and heteroskedastic models
      with error-prone covariates.

PMID- 29200599
TI  - Expression Levels and Localizations of DVL3 and sFRP3 in Glioblastoma.
AB  - The expression patterns of critical molecular components of Wnt signaling, sFRP3
      and DVL3, were investigated in glioblastoma, the most aggressive form of primary
      brain tumors, with the aim to offer potential biomarkers. The protein expression
      levels and localizations in tumor tissue were revealed by immunohistochemistry
      and evaluated by the semiquantitative method and immunoreactivity score. Majority
      of glioblastomas had moderate expression levels for both DVL3 (52.4%) and sFRP3
      (52.3%). Strong expression levels were observed in 23.1% and 36.0% of samples,
      respectively. DVL3 was localized in cytoplasm in 97% of glioblastomas, of which
      44% coexpressed the protein in the nucleus. sFRP3 subcellular distribution showed
      that it was localized in the cytoplasm in 94% of cases. Colocalization in the
      cytoplasm and nucleus was observed in 50% of samples. Wilcox test indicated that
      the domination of the strong signal is in connection with simultaneous
      localization of DVL3 protein in the cytoplasm and the nucleus. Patients with
      strong expression of DVL3 will significantly more often have the protein in the
      nucleus (P = 6.33 * 10-5). No significant correlation between the two proteins
      was established, nor were their signal strengths correlated with epidemiological
      parameters. Our study contributes to better understanding of glioblastoma
      molecular profile.

PMID- 29200601
TI  - Response of Brassica oleracea to temporal variation in attack by two herbivores
      affects preference and performance of a third herbivore.
AB  - 1. Plants are frequently under attack by multiple insect herbivores, which may
      interact indirectly through herbivore-induced changes in the plant's phenotype.
      The identity, order, and timing of herbivore arrivals may influence the outcome
      of interactions between two herbivores. How these aspects affect, in turn,
      subsequently arriving herbivores that feed on double herbivore-induced plants has
      not been widely investigated. 2. This study tested whether the order and timing
      of arrival of two inducing herbivores from different feeding guilds affected the
      preference and performance of a subsequently arriving third herbivore,
      caterpillars of Mamestra brassicae L. (Lepidoptera: Noctuidae). Aphids
      [Brevicoryne brassicae L. (Hemiptera: Aphididae)] and caterpillars [Plutella
      xylostella L. (Lepidoptera: Yponomeutidae)] were introduced onto wild Brassica
      oleracea L. (Brassicaceae) plants in different sequences and with different
      arrival times. The effects of these plant treatments on M. brassicae caterpillars
      were assessed in pairwise preference tests and no-choice performance tests. 3.
      The caterpillars of M. brassicae preferred to feed from undamaged plants rather
      than double herbivore-induced plants. Compared with undamaged plants, they
      preferred plant material on which aphids had arrived first followed by
      caterpillars, whereas they avoided plant material with the reverse order of
      herbivore arrival. Performance of the caterpillars increased with increasing
      arrival time between herbivore infestations in double herbivore-induced plants.
      Although M. brassicae grew faster on plants induced by aphids than on those
      induced by caterpillars alone, its performance was not affected by the order of
      previous herbivore arrival. 4. These results imply that the timing of
      colonisation by multiple herbivores determines the outcome of plant-mediated
      herbivore-herbivore interactions.

PMID- 29200602
TI  - Does similarity in call structure or foraging ecology explain interspecific
      information transfer in wild Myotis bats?
AB  - Abstract: Animals can gain important information by attending to the signals and
      cues of other animals in their environment, with acoustic information playing a
      major role in many taxa. Echolocation call sequences of bats contain information
      about the identity and behaviour of the sender which is perceptible to close-by
      receivers. Increasing evidence supports the communicative function of
      echolocation within species, yet data about its role for interspecific
      information transfer is scarce. Here, we asked which information bats extract
      from heterospecific echolocation calls during foraging. In three linked playback
      experiments, we tested in the flight room and field if foraging Myotis bats
      approached the foraging call sequences of conspecifics and four heterospecifics
      that were similar in acoustic call structure only (acoustic similarity
      hypothesis), in foraging ecology only (foraging similarity hypothesis), both, or
      none. Compared to the natural prey capture rate of 1.3 buzzes per minute of bat
      activity, our playbacks of foraging sequences with 23-40 buzzes/min simulated
      foraging patches with significantly higher profitability. In the flight room, M.
      capaccinii only approached call sequences of conspecifics and of the
      heterospecific M. daubentonii with similar acoustics and foraging ecology. In the
      field, M. capaccinii and M. daubentonii only showed a weak positive response to
      those two species. Our results confirm information transfer across species
      boundaries and highlight the importance of context on the studied behaviour, but
      cannot resolve whether information transfer in trawling Myotis is based on
      acoustic similarity only or on a combination of similarity in acoustics and
      foraging ecology. Significance statement: Animals transfer information, both
      voluntarily and inadvertently, and within and across species boundaries. In
      echolocating bats, acoustic call structure and foraging ecology are linked,
      making echolocation calls a rich source of information about species identity,
      ecology and activity of the sender, which receivers might exploit to find
      profitable foraging grounds. We tested in three lab and field experiments if
      information transfer occurs between bat species and if bats obtain information
      about ecology from echolocation calls. Myotis capaccinii/daubentonii bats
      approached call playbacks, but only those from con- and heterospecifics with
      similar call structure and foraging ecology, confirming interspecific information
      transfer. Reactions differed between lab and field, emphasising situation
      dependent differences in animal behaviour, the importance of field research, and
      the need for further studies on the underlying mechanism of information transfer
      and the relative contributions of acoustic and ecological similarity.

PMID- 29200603
TI  - Domestic violence shapes Colombian women's partner choices.
AB  - Abstract: Potential protection from violence has been suggested as an explanation
      for women's preferences for more masculine partners. Previous studies, however,
      have not considered that violence may be multi-modal, and hence come from
      different sources. Therefore, we tested the effect of different fears of violence
      (i.e. vulnerability to public crime, likelihood of within-partnership violence)
      on masculinity preferences of women from Colombia, a country known for its high
      rates of violence. Eighty-three adult heterosexual women (mean age +/- SD = 26.7
      +/- 6.01) answered a survey that included questions about health (e.g. frequency
      of illnesses during the last year and during childhood), access to media (e.g.
      time spent watching television, frequency of internet use), education (i.e.
      highest level achieved) and violence perceptions. Participants' masculinity
      preferences for Salvadoran, European and Colombian male faces were recorded.
      Factor analysis revealed two different factors for the answers to questions
      related to violence. One factor loaded mostly on questions related to public
      violence and the second factor related to domestic violence. We found that women
      with higher scores on the domestic violence factor preferred significantly less
      masculine Colombian male faces. Even after controlling for participant age,
      education, access to media (TV and internet) and health-related factors, the
      domestic violence factor contributed significantly to explaining masculinity
      preferences. The results presented here suggest that women's preferences for
      masculinity may be a strategy to avoid aggressive partners and that the source of
      violence matters in mate choice. Significance statement: Women who perceive
      higher risks of domestic violence prefer less masculine looking partners. Using
      an experimental approach, we show that Colombian women who feel more in danger of
      violence within partnership prefer the faces of less masculine males. This was
      true even after controlling for women's education level, health and access to
      media.

PMID- 29200604
TI  - Genetic impact of Rht dwarfing genes on grain micronutrients concentration in
      wheat.
AB  - Wheat is a major staple food crop providing about 20% of dietary energy and
      proteins, and food products made of whole grain wheat are a major source of
      micronutrients like Zinc (Zn), Iron (Fe), Manganese (Mn), Magnesium (Mg), Vitamin
      B and E. Wheat provides about 40% intake of essential micronutrients by humans in
      the developing countries relying on wheat based diets. Varieties with genetically
      enhanced levels of grain micronutrient concentrations can provide a cost
      effective and sustainable option to resource poor wheat consumers. To determine
      the effects of commonly deployed dwarfing genes on wheat grain Zn, Fe, Mn and Mg
      concentrations, nine bread wheat (Triticum aestivum) and six durum wheat (T.
      turgidum) isoline pairs differing for Rht1 (= Rht-B1b) and one bread wheat pair
      for Rht2 (= Rht-D1b) dwarfing genes were evaluated for three crop seasons at N.E.
      Borlaug Research Station, Cd. Obregon, Sonora, Mexico. Presence of dwarfing genes
      have significantly reduced grain Zn concentration by 3.9 ppm (range 1.9-10.0
      ppm), and Fe by 3.2 ppm (range 1.0-14.4 ppm). On the average, about 94 ppm Mg and
      6 ppm Mn reductions occurred in semidwarf varieties compared to tall varieties.
      The thousand kernel weight (TKW) of semidwarf isolines was 2.6 g (range 0.7-5.6
      g) lower than the tall counterparts whereas the plant height decreased by 25 cm
      (range 16-37 cm). Reductions for all traits in semidwarfs were genotype dependent
      and the magnitude of height reductions did not correlate with reductions in
      micronutrient concentrations in wheat grain. We conclude that increased grain
      yield potential of semidwarf wheat varieties is associated with reduced grain
      micronutrient concentrations; however, the magnitude of reductions in
      micronutrients varied depending on genetic background and their associated
      pleiotropic effect on yield components.

PMID- 29200605
TI  - Agent-Based Modeling of China's Rural-Urban Migration and Social Network
      Structure.
AB  - We analyze China's rural-urban migration and endogenous social network structures
      using agent-based modeling. The agents from census micro data are located in
      their rural origin with an empirical-estimated prior propensity to move. The
      population-scale social network is a hybrid one, combining observed family ties
      and locations of the origin with a parameter space calibrated from census, survey
      and aggregate data and sampled using a stepwise Latin Hypercube Sampling method.
      At monthly intervals, some agents migrate and these migratory acts change the
      social network by turning within-nonmigrant connections to between-migrant
      nonmigrant connections, turning local connections to nonlocal connections, and
      adding among-migrant connections. In turn, the changing social network structure
      updates migratory propensities of those well-connected nonmigrants who become
      more likely to move. These two processes iterate over time. Using a core
      periphery method developed from the k-core decomposition method, we identify and
      quantify the network structural changes and map these changes with the migration
      acceleration patterns. We conclude that network structural changes are essential
      for explaining migration acceleration observed in China during the 1995-2000
      period.

PMID- 29200606
TI  - Bayesian penalized spline model-based inference for finite population proportion
      in unequal probability sampling.
AB  - We propose a Bayesian Penalized Spline Predictive (BPSP) estimator for a finite
      population proportion in an unequal probability sampling setting. This new method
      allows the probabilities of inclusion to be directly incorporated into the
      estimation of a population proportion, using a probit regression of the binary
      outcome on the penalized spline of the inclusion probabilities. The posterior
      predictive distribution of the population proportion is obtained using Gibbs
      sampling. The advantages of the BPSP estimator over the Hajek (HK), Generalized
      Regression (GR), and parametric model-based prediction estimators are
      demonstrated by simulation studies and a real example in tax auditing. Simulation
      studies show that the BPSP estimator is more efficient, and its 95% credible
      interval provides better confidence coverage with shorter average width than the
      HK and GR estimators, especially when the population proportion is close to zero
      or one or when the sample is small. Compared to linear model-based predictive
      estimators, the BPSP estimators are robust to model misspecification and
      influential observations in the sample.

PMID- 29200607
TI  - Bayesian inference for finite population quantiles from unequal probability
      samples.
AB  - This paper develops two Bayesian methods for inference about finite population
      quantiles of continuous survey variables from unequal probability sampling. The
      first method estimates cumulative distribution functions of the continuous survey
      variable by fitting a number of probit penalized spline regression models on the
      inclusion probabilities. The finite population quantiles are then obtained by
      inverting the estimated distribution function. This method is quite
      computationally demanding. The second method predicts non-sampled values by
      assuming a smoothly-varying relationship between the continuous survey variable
      and the probability of inclusion, by modeling both the mean function and the
      variance function using splines. The two Bayesian spline-model-based estimators
      yield a desirable balance between robustness and efficiency. Simulation studies
      show that both methods yield smaller root mean squared errors than the sample
      weighted estimator and the ratio and difference estimators described by Rao,
      Kovar, and Mantel (RKM 1990), and are more robust to model misspecification than
      the regression through the origin model-based estimator described in Chambers and
      Dunstan (1986). When the sample size is small, the 95% credible intervals of the
      two new methods have closer to nominal confidence coverage than the sample
      weighted estimator.

PMID- 29200608
TI  - A nonparametric method to generate synthetic populations to adjust for complex
      sampling design features.
AB  - Outside of the survey sampling literature, samples are often assumed to be
      generated by a simple random sampling process that produces independent and
      identically distributed (IID) samples. Many statistical methods are developed
      largely in this IID world. Application of these methods to data from complex
      sample surveys without making allowance for the survey design features can lead
      to erroneous inferences. Hence, much time and effort have been devoted to develop
      the statistical methods to analyze complex survey data and account for the sample
      design. This issue is particularly important when generating synthetic
      populations using finite population Bayesian inference, as is often done in
      missing data or disclosure risk settings, or when combining data from multiple
      surveys. By extending previous work in finite population Bayesian bootstrap
      literature, we propose a method to generate synthetic populations from a
      posterior predictive distribution in a fashion inverts the complex sampling
      design features and generates simple random samples from a superpopulation point
      of view, making adjustment on the complex data so that they can be analyzed as
      simple random samples. We consider a simulation study with a stratified,
      clustered unequal-probability of selection sample design, and use the proposed
      nonparametric method to generate synthetic populations for the 2006 National
      Health Interview Survey (NHIS), and the Medical Expenditure Panel Survey (MEPS),
      which are stratified, clustered unequal-probability of selection sample designs.

PMID- 29200609
TI  - Combining information from multiple complex surveys.
AB  - This manuscript describes the use of multiple imputation to combine information
      from multiple surveys of the same underlying population. We use a newly developed
      method to generate synthetic populations nonparametrically using a finite
      population Bayesian bootstrap that automatically accounting for complex sample
      designs. We then analyze each synthetic population with standard complete-data
      software for simple random samples and obtain valid inference by combining the
      point and variance estimates using extensions of existing combining rules for
      synthetic data. We illustrate the approach by combining data from the 2006
      National Health Interview Survey (NHIS) and the 2006 Medical Expenditure Panel
      Survey (MEPS).

PMID- 29200610
TI  - Investigations of medium-temperature heat treatments to achieve low outgassing
      rates in stainless steel ultrahigh vacuum chambers.
AB  - The authors investigated the outgassing rates and fluxes of vacuum chambers
      constructed from common 304L stainless steel vacuum components and subjected to
      heat treatments. Our goal was to obtain H2 outgassing flux on the order of 10-11
      Pa l s-1cm-2 or better from standard stainless steel vacuum components readily
      available from a variety of manufacturers. The authors found that a medium
      temperature bake in the range of 400 to 450 degrees C, performed with the
      interior of the chamber under vacuum, was sufficient to produce the desired
      outgassing flux. The authors also found that identical vacuum components baked in
      air at the same temperature for the same amount of time did not produce the same
      low outgassing flux. In that case, the H2 outgassing flux was lower than that of
      a stainless-steel chamber with no heat treatment, but was still approximately 1
      order of magnitude higher than that of the medium-temperature vacuum-bake.
      Additionally, the authors took the chamber that was subjected to the medium
      temperature vacuum heat treatment and performed a 24-h air bake at 430 degrees C.
      This additional heat treatment lowered the outgassing rate by nearly a factor of
      two, which strongly suggests that the air-bake created an oxide layer which
      reduced the hydrogen recombination rate on the surface.
      [http://dx.doi.org/10.1116/1.4983211].

PMID- 29200611
TI  - Serial position, output order, and list length effects for words presented on
      smartphones over very long intervals.
AB  - Three experiments examined whether or not benchmark findings observed in the
      immediate retrieval from episodic memory are similarly observed over much greater
      time-scales. Participants were presented with experimentally-controlled lists of
      words at the very slow rate of one word every hour using an iPhone recall
      application, RECAPP, which was also used to recall the words in either any order
      (free recall: Experiments 1 to 3) or the same order as presented (serial recall:
      Experiment 3). We found strong temporal contiguity effects, weak serial position
      effects with very limited recency, and clear list length effects in free recall;
      clear primacy effects and classic error gradients in serial recall; and recency
      effects in a final two-alternative forced choice recognition task (Experiments 2
      and 3). Our findings extend the timescales over which temporal contiguity effects
      have been observed, but failed to find consistent evidence for strong long-term
      recency effects with experimenter-controlled stimuli.

PMID- 29200612
TI  - Being Superwoman: Low income mothers surviving problem drinking and intimate
      partner violence.

PMID- 29200613
TI  - MECHANICAL TESTING OF A PHOTOCURED CHOPPED FIBER REINFORCED DENTAL COMPOSITE.
AB  - The objective was to validate strength improvements by incorporating chopped
      fiber into commercial particulate filled visible-light cured dental pastes.
      Photocurable resin preimpregnated 3-mm high purity quartz fibers were blended
      into two universal commercial composites, 3M Corp. Z100 and Kerr Corp. XRV at 35
      wt% fiber. Four groups, consisting of the Z100 and XRV controls, along with Z100
      and XRV both containing fibers, were prepared in a mold 2*2*25-mm then cured at
      equivalent irradiation intensities monitored by a Demetron Radiometer. Evaluation
      was accomplished on ten specimens from the four different categories according to
      ASTM Standard C 1161-94 configuration-A utilizing a fully-articulated four-point
      bend fixture and 20-mm span. Five samples out of each group were further assessed
      using a modified Izod Plastic Impact Tester per ASTM D 256-00. Both highly
      strengthened fiber reinforced composites attained a marginal error of uncertainty
      for statistical significance over the commercial controls (p=0.001 AVOVA posthoc
      Newman-Keuls) with maximum bending stress, flexural modulus, work of fracture and
      Izod impact toughness. From the results, it can be concluded that photocured
      chopped fiber reinforced composites will produce improvements over particulate
      filled compounds that can be considered breakthrough.

PMID- 29200614
TI  - Connected: Recommendations and Techniques in Order to Employ Internet Tools for
      the Enhancement of Online Therapeutic Relationships. Experiences from Italy.
AB  - The article explores the different types of therapeutic relationship that can
      evolve both on- and offline, thanks to the use of tools, such as software and
      applications, which enable therapists and patients contact outside of the
      traditional setting. Given the premise that it is practically impossible today to
      maintain a relationship without the use of internet and telephones, it becomes
      necessary to question the ways in which the online space can become a useful
      extension of the therapeutic setting. The authors, starting from a consideration
      regarding the specificity of the online therapeutic relationship, analyze the
      best ways to use text and email messaging with patients. Furthermore, specific
      interactions via group chats are presented, for example, to coordinate a
      therapeutic team involving several professionals. Further, video chat settings
      are discussed through a clinical case presentation. Lastly, the therapist's
      management of social networks is debated, underscoring the importance for the
      therapists that his or her online identity be consistent with the offline image
      which patients are introduced to in the traditional setting of the therapy room.

PMID- 29200615
TI  - Time Use During First Year of College Predicts Participation in High-Impact
      Activities During Later Years.

PMID- 29200616
TI  - Electromyographic analysis of constraint-induced movement therapy effects in
      patients after stroke in chronic course.
AB  - [Purpose] The purpose is to analyze the effects of Constraint-induced Movement
      Therapy in post stroke patients in chronic course. [Subjects and Methods] This is
      a Quasi-experiment study and the adopted protocol consisted of a three-hour
      therapy for ten consecutive working days applied to a constraint intact upper
      limb. Surface Electromyography, Motor Activity Log, Wolf Motor Function Test and
      Functional Independence Measure were used for evaluating the experiment.
      [Results] The individuals showed reduction in the degree of spasticity, confirmed
      by Surface Electromyography. In relation to Motor Activity Log this study showed
      an increase in amount and in quality of the paretic upper limb movement. The Wolf
      Motor Function Test showed reduction in the average time to perform the tasks and
      a functional improvement was identified through the Functional Independence
      Measure. [Conclusion] Constraint Induced Movement Therapy proved to be a relevant
      method to improve motor function in chronic hemiparesis post stroke reducing the
      spasticity, maximizing and improving the use of committed upper limb.

PMID- 29200617
TI  - The relationship between bruxism, sleep quality, and headaches in schoolchildren.
AB  - [Purpose] Present study aimed to evaluate the relationship between sleep bruxism
      and headache in school children. [Subjects and Methods] This study was conducted
      with 103 children aged 3-6 years. The exclusion criteria were early tooth loss,
      dental appliance was used, physical or psychological limitations, chronic disease
      and continuous medication. Sleep bruxism was diagnosed based on an indication by
      parents of the occurrence of teeth clenching/grinding and incisor/occlusal tooth
      wear, following the criteria of the American Academy of Sleep Medicine. Sleep
      quality was evaluated by a questionnarie, detailing the child's sleep
      characteristics. [Results] Forty-nine children (47.6%) were diagnosed with sleep
      bruxism. Those with sleep bruxism were 3.25-fold more likely to present headache.
      Children whose parents were separated had a significantly greater frequency of
      sleep bruxism and primary headache. The relative risk of exhibiting primary
      headache was 13.1 among children with sleep bruxism whose parents were separated.
      [Conclusion] Children with SB demonstrated a greater risk of having primary
      headache and those whose parents were separated had a greater chance of having
      headache. Only sleep bruxism was associated with headache, clenching the teeth
      during waking hours was not correlated with primary headache.

PMID- 29200618
TI  - Effects of individual and group exercise programs on pain, balance, mobility and
      perceived benefits in rheumatoid arthritis with pain and foot deformities.
AB  - [Purpose] To verify the effects of individual and group exercise programs on
      pain, balance, mobility and perceived benefits of rheumatoid arthritis patients
      (RA) with pain and foot deformities. [Subjects and Methods] Thirty patients with
      RA pain and foot deformity were allocated into two groups: G1: individual
      exercise program and G2: group exercise program. The variables analyzed were
      Numerical Rating Scale (NRS) for pain, Berg Balance Scale (BBS) for balance,
      Timed Up & Go Test (TUG) and Functional Reach (FR) for mobility, and Foot Health
      Status Questionnaire (FHSQ-Br) for perceived benefits. Both exercise programs
      consisted of functional rehabilitation exercises and self-care guidance aimed at
      reducing pain and improving balance and mobility. Intragroup comparisons of
      variables between A1 (pre-intervention) and A2 (post-intervention) were
      performed. [Results] Patients in both groups were similar in A1 (pre
      intervention) in all the variables analyzed. Comparison between A1 and A2 for
      each variable showed improvement for G1 in the NRS, BBS, FR, TUG and in four out
      of ten domains of FHSQ-Br. G2 showed improvement in the NRS, BBS and eight out of
      ten domains of FHSQ-Br. [Conclusion] Both individual and group programs revealed
      benefits for patients with RA, however, group exercise programs showed better
      perception of benefits.

PMID- 29200619
TI  - The effect of newly designed multi joint ankle foot orthosis on the gait and
      dynamic balance of stroke patients with foot drop.
AB  - [Purpose] The purpose of this study is to investigate the effect of the newly
      designed multi joint ankle-foot orthosis on the gait and dynamic balance of
      stroke patients having foot drop. [Subjects and Methods] This study was conducted
      with 15 subjects who were diagnosed with stroke. 10-meter walk test, functional
      reaching test and timed up and go test were measured after each subjects wore a
      plastic ankle-foot orthosis and a multi joint ankle-foot orthosis that consists
      of orthosis joints (having free joint, anterior-stop joint, poster-stop joint,
      and Klenzak joint functions). In the case of the newly developed multi joint
      ankle-foot orthosis, the experiments were performed using posterior-stop joint
      and Klenzak joint. [Results] 10-meter walk test, functional reaching test and
      timed up and go test showed significant differences in the orthosis using
      posterior joint-stop function and Klenzak joint function. [Conclusion] The
      appropriate use of the four functions of the newly designed multi joint ankle
      foot orthosis is expected to have a positive effect on improving the gait and
      balancing ability of stroke patients having foot drop.

PMID- 29200620
TI  - Effects of open and closed kinetic-chain exercises on the muscle strength and
      muscle activity of the ankle joint in young healthy women.
AB  - [Purpose] The purpose of this study was to analyze the effects of open and closed
      chain exercise on the muscle strength and muscle activity of the ankle joint.
      [Subjects and Methods] Twenty women in their 20s were randomly assigned to two
      groups: the open kinetic-chain group and the closed kinetic-chain group. Each
      group performed 5 sets 3 times per week for 4 weeks. Exercise intensity was
      increased once after two weeks. The muscle activity of the tibialis anterior,
      gastrocnemius, tibialis posterior, and peroneus longus muscles were measured. The
      collected data were analyzed with two-way repeated measures ANOVA. [Results] In
      the results for muscle strength, both groups showed significant differences in
      dorsiflexion and plantar flexion between the pre-test and post-test. In the
      results for muscle activity, no significant differences were noted for either
      group. [Conclusion] Open and closed kinetic-chain exercises can help to improve
      muscle strength.

PMID- 29200621
TI  - The effects of extracorporeal shock wave therapy on pain and range of motion in
      patients with adhesive capsulitis.
AB  - [Purpose] This study examined the effects of extracorporeal shock wave therapy on
      pain and range of motion in patients with adhesive capsulitis. [Subjects and
      Methods] Thirty patients with adhesive capsulitis were divided into an
      experimental group (n=15) that would be treated with extracorporeal shock wave
      therapy and a control group (n=15) that would be treated only with conservative
      physical therapy. Both groups were treated three times a week over a four-week
      period. [Results] An intra-group comparison before and after the treatment showed
      that both groups experienced a decline in pain and an increase in their range of
      motion that were statistically significant. An inter-group comparison after the
      treatment showed that the experimental group had a lower level of pain and a
      higher range of motion than the control group that were statistically
      significant. [Conclusion] Extracorporeal shock wave therapy may be an effective
      intervention for reducing pain and improving the range of motion in patients with
      adhesive capsulitis.

PMID- 29200622
TI  - Nutritional status and management of risks due to physical therapy in patients
      hospitalized for long periods.
AB  - [Purpose] This study aimed to understand the nutritional status of patients
      hospitalized for long periods and the risk of physical therapy (PT) for such
      patients. [Subjects and Methods] Participants were selected from patients who
      were hospitalized at a designated medical long-term care sanatorium. The
      participants were divided into 5 groups (A-E) depending on their mode of energy
      intake and ambulatory ability during PT. The serum albumin level, energy intake,
      total daily energy expenditure, and total daily energy expenditure per session of
      PT (EEPT) were evaluated for each group. [Results] Protein-energy malnutrition
      was observed in 69.6% of the participants. No significant association was
      identified between the serum albumin level and body mass index. Energy intake was
      significantly higher in Groups D and E, whose energy intake was via ingestion,
      than in Groups A and B, whose intake was via tube feeding. EEPT was highest in
      patients of Group E who had gait independence different from the ability of those
      in groups A-D. [Conclusion] The actual energy intake is lower with tube feeding
      than with ingestion. Risk management and energy intake should be revisited in
      elderly patients who have been hospitalized for long periods and subsequently
      obtain gait independence.

PMID- 29200623
TI  - Effect of fingernail length on the hand dexterity.
AB  - [Purpose] The fingernails allow for increased sensory perception at the finger
      pulp, and contribute to the accurate picking up of small objects. The purpose of
      the present study was to clarify the effect of fingernail length on hand
      dexterity using subjects' own fingernails. [Subjects and Methods] The hand sizes
      and fingernail configurations of 38 young healthy volunteers (eighteen males and
      twenty females) were measured. The effect of fingernail length (0 and 2 mm) on
      hand dexterity also was investigated using the simple test for evaluating hand
      function. [Results] The hand and finger sizes as well as fingernail widths were
      significantly larger in males than in females. The time taken for each subtest of
      the simple test for evaluating hand function was generally shorter at a
      fingernail length of 2 mm than at 0 mm, and it was significantly shorter for a
      number of subtests. There was little significant difference in the time taken for
      the subtests between genders. [Conclusion] It was clear that a fingernail length
      of 2 mm had an advantageous effect on hand dexterity, with little gender
      difference observed. These findings suggest that the fingernail lengths of the
      subjects should be standardized when evaluating changes in their hand dexterity
      with time.

PMID- 29200624
TI  - Exercise using a robotic knee orthosis in stroke patients with hemiplegia.
AB  - [Purpose] The Robotics Knee Orthosis (RKO) is a knee-ankle-foot orthosis with
      active robot assisting technology. The purpose of this study is to examine the
      effects of exercise with the RKO (RKO-exercise) in stroke patients with
      hemiplegia. [Subjects and Methods] Participants were nine stroke patients with
      hemiplegia, residing in a convalescent rehabilitation ward. The duration of the
      RKO-exercise program was 10 days. Participants were evaluated three times prior
      to intervention, once after intervention, and one month post intervention. Each
      session consisted of standard-of-care physical therapy for 60 minutes and RKO
      exercise for 20 minutes. Dependent variables were 10-meter gait speed, cadence,
      Berg Balance Scale (BBS) score, stride length, the absolute value of left-right
      symmetry of the step length, and one-leg support period while walking. Data were
      analyzed using a one-way repeated measures ANOVA. [Results] Stride length, left
      right symmetry of the step length, and one-leg support period while walking
      changed following the RKO exercise program. 10-meter walking speed, cadence,
      percentage of one-leg support period (affected side), and BBS changed
      significantly at one month post treatment time points. [Conclusion] It is
      expected that RKO-exercise helps recovery process after the stroke. RKO-exercise
      effectively treats impaired mobility in patient status-post stroke.

PMID- 29200625
TI  - Large calf circumference indicates non-sarcopenia despite body mass.
AB  - [Purpose] The purpose of this study is to evaluate the applicability of the calf
      circumference as a tool for screening sarcopenia. [Subjects and Methods] One
      hundred sixteen community-dwelling elderly females were enrolled. Calf
      circumference of the dominant leg was measured using a plastic measuring tape.
      Subjects were divided into 3 groups based on body mass index (BMI); subjects with
      the values for BMI <18.5 kg/m2; those with BMI 18.5 to 25.0; those with BMI
      >=25.0 kg/m2. Positive predictive value and negative predictive value of
      sarcopenia were calculated based on the obtained cut off values of calf
      circumference and the diagnosis of sarcopenia in each group. [Results] Prevalence
      rate of sarcopenia was 9.4% (n=10). Cut off value of the calf circumference was
      32.8 cm (sensitivity: 73.0%, specificity: 80.0%, AUC: 0.792). Each BMI group
      showed high negative predictive value of sarcopenia based on the calf
      circumference cut off value of 32.8 cm. [Conclusion] These results suggested that
      to identify non-sarcopenia by larger calf circumference is more reasonable and
      useful than to identify sarcopenia due to the smaller calf circumference
      regardless of BMI.

PMID- 29200626
TI  - The effects of tongue stretching exercise on tongue length in healthy adults: a
      preliminary study.
AB  - [Purpose] The purpose of this study was to investigate the effects of tongue
      stretching exercise on the tongue length of healthy adults. [Subjects and
      Methods] This study recruited 6 healthy adults. They were treated for 4 weeks
      with tongue stretching. The change in tongue length during tongue protrusion
      before and after intervention was measured using a ruler. [Results] All 6
      participants showed increased tongue length (minimum 20 mm to maximum 40 mm).
      [Conclusion] This study confirms that tongue stretching is a useful method to
      increase tongue length.

PMID- 29200627
TI  - Effect of motor imagery training and electromyogram-triggered neuromuscular
      electrical stimulation on lower extremity function in stroke patients: a pilot
      trial.
AB  - [Purpose] To investigate the effect of motor imagery training and electromyogram
      triggered neuromuscular electrical stimulation (MIT-EMG NMES) on the lower
      extremity function of stroke patients. [Subjects and Methods] This study
      recruited eight patients with hemiplegia due to stroke. All patients received MIT
      EMG NMES for 20 min daily, 5 days per week for 4 weeks. Lower extremity function
      were assessed using the timed up-and-go (TUG) and 10-meter walk (10MW) tests.
      [Results] The results of TUG test decreased significantly from 20.5 +/- 4.5 to
      14.0 +/- 3.5 s, while those of 10 MW test showed a significant decrease from 21.3
      +/- 4.5 to 15.5 +/- 3.2 m. [Conclusion] This study suggests that MIT-EMG NMES is
      a new rehabilitation therapy for lower extremity recovery in hemiplegic stroke
      patients.

PMID- 29200628
TI  - The Korean version of relative and absolute reliability of gait and balance
      assessment tools for patients with dementia in day care center and nursing home.
AB  - [Purpose] This study was aimed to determine the relative and absolute reliability
      of Korean version tools of the Berg Balance Scale (BBS), the Timed Up and Go
      (TUG), the Four-Meter Walking Test (4MWT) and the Groningen Meander Walking Test
      (GMWT) in patients with dementia. [Subjects and Methods] A total of 53 patients
      with dementia were tested on TUG, BBS, 4MWT and GMWT with a prospective cohort
      methodological design. Intra-class Correlation Coefficients (ICCs) to assess
      relative reliability and the standard error of measurement (SEM), minimal
      detectable change (MDC95) and its percentage (MDC%) to analyze the absolute
      reliability were calculated. [Results] Inter-rater reliability (ICC(2,3)) of TUG,
      BBS and GMWT was 0.99 and that of 4MWT was 0.82. Inter-rater reliability was high
      for TUG, BBS and GMWT, with low SEM, MDC95, and MDC%. Inter-rater reliability was
      low for 4MWT, with high SEM, MDC95, and MDC%. Test-retest (ICC(2,3)) of TUG, BBS
      and GMWT was 0.96-0.99 and Test-retest (ICC(2,3)) of 4MWT was 0.85. The test
      retest was high for TUG, BBS and GMWT, with low SEM, MDC95, and MDC%, but it was
      low for 4MWT, with high SEM, MDC95, and MDC%. [Conclusion] The relative
      reliability was high for all the assessment tools. The absolute reliability has a
      reasonable level of stability except the 4MWT.

PMID- 29200629
TI  - Trunk lean gait decreases multi-segmental coordination in the vertical direction.
AB  - [Purpose] The strategy of trunk lean gait to reduce external knee adduction
      moment (KAM) may affect multi-segmental synergy control of center of mass (COM)
      displacement. Uncontrolled manifold (UCM) analysis is an evaluation index to
      understand motor variability. The purpose of this study was to investigate how
      motor variability is affected by using UCM analysis on adjustment of the trunk
      lean angle. [Subjects and Methods] Fifteen healthy young adults walked at their
      preferred speed under two conditions: normal and trunk lean gait. UCM analysis
      was performed with respect to the COM displacement during the stance phase. The
      KAM data were analyzed at the points of the first KAM peak during the stance
      phase. [Results] The KAM during trunk lean gait was smaller than during normal
      gait. Despite a greater segmental configuration variance with respect to
      mediolateral COM displacement during trunk lean gait, the synergy index was not
      significantly different between the two conditions. The synergy index with
      respect to vertical COM displacement during trunk lean gait was smaller than that
      during normal gait. [Conclusion] These results suggest that trunk lean gait is
      effective in reducing KAM; however, it may decrease multi-segmental movement
      coordination of COM control in the vertical direction.

PMID- 29200630
TI  - Changes in lower limb muscle activity based on angle of ankle abduction during
      lunge exercise.
AB  - [Purpose] This study compared the activity of the quadriceps femoris muscle
      according to the angle of ankle abduction during a lunge exercise. [Subjects and
      Methods] Fifteen male healthy volunteers participated in the study. All
      participants performed the lunge exercise with different angles of ankle
      abduction (0 degrees , 20 degrees , 40 degrees , 60 degrees ). The activity of
      the rectus femoris (RF), vastus lateralis (VL) and vastus medialis oblique (VMO)
      muscles were recorded for the four angles by using a surface electromyography
      system. [Results] There were significant differences between the rectus femoris
      (RF), vastus lateralis (VL) and vastus medialis oblique (VMO) with every angle of
      the ankle joint. The most significantly increased muscle activity was evident in
      the vastus medialis oblique (VMO) when the ankle abduction was 60 degrees .
      [Conclusion] These findings suggest that as the ankle abduction angle increases
      during the lunge exercise, the muscle activity of the quadriceps femoris muscle
      increases and this could be helpful in the selective muscle strengthening of the
      vastus medialis oblique muscle (VMO) with the ankle in the 60 degrees  abduction
      position.

PMID- 29200631
TI  - The effects of aging on the subjective vertical in the frontal plane in healthy
      adults.
AB  - [Purpose] To determine age-related differences in the subjective vertical in the
      frontal plane in healthy adults. [Subjects and Methods] The subjects were 26
      healthy adults. For the subjective visual vertical (SVV), subjects were presented
      with a visual indicator in front of them that was rotated. For the subjective
      postural vertical-eyes open (SPV-EO) and subjective postural vertical (SPV),
      subjects sat in a seating device that was tilted right or left. The subjects gave
      a signal when they perceived true verticality. Each task was performed eight
      times. The items examined were the mean (tilt direction) and standard deviation
      (variability) of the eight trials, then the mean of four trials that started from
      the right or left side position. These items were compared between the young
      (age: 22-30 years [range]) and elderly (age: 60-74 years) groups. [Results] As
      for variability, the elderly group demonstrated significantly higher values of
      SPV-EO and SPV. As for the starting point effect, the elderly group demonstrated
      greater bias toward the starting direction than did the young group in SPV-EO and
      SPV in frontal plane. [Conclusion] The postural vertical was shown to change with
      age. Consideration of age-related changes and the starting point effect was
      indicated to be important.

PMID- 29200632
TI  - The effect of the inspiratory muscle training on functional ability in stroke
      patients.
AB  - [Purpose] This study was to find out an inspiratory muscle training (IMT) program
      therapeutic effects on stroke patients' functional ability. [Subjects and
      Methods] Twenty stroke patients were assigned to one of two groups: inspiratory
      muscle training (n=10), and control (n=10), randomization. The inspiratory muscle
      training participants undertook an exercise program for 30 minute per times, 5
      times a week for 6 weeks. The investigator measured the patients' trunk
      impairment scale (TIS) and 6 minute walking test (6MW) for functional ability
      before and after IMT. [Results] The TIS appeared some significant differences in
      both groups before and after the training. The 6MW test showed some significant
      differences in the inspiratory muscle training group, but didn't show any
      significant difference in the control group. And the differences in both groups
      after depending the inspiratory muscle training were significantly found in the
      tests of TIS and 6MW test [Conclusion] The results showed that the inspiratory
      muscle training in stroke patients are correlated with the trunk stability and
      locomotion ability, suggesting that physical therapist must take into
      consideration the inspiratory muscle training, as well as functional training to
      improve physical function in stroke patients.

PMID- 29200633
TI  - Effects of silver gymnastic exercises on aging-related hormones in elderly women
      living alone.
AB  - [Purpose] The purpose of this study was to investigate the effect of silver
      gymnastic exercises on aging-related hormones in elderly women living alone.
      [Subjects and Methods] The study group consisted of 20 elderly women living alone
      who performed the silver gymnastic exercises for 12 weeks. Blood samples were
      obtained for measurement of aging-related hormones (human growth hormone [HGH]
      and estrogen). [Results] HGH and estrogen levels increased significantly after
      the exercise program as compared to before the program. [Conclusion] The silver
      gymnastic exercises helped to induce positive changes in aging-related hormone
      levels in elderly women living alone. These positive effects on aging-related
      hormones might help to slow down aging in elderly women living alone.

PMID- 29200634
TI  - The immediate effects of rib cage joint mobilization and chest wall stretch on
      muscle tone and stiffness of respiratory muscles and chest expansion ability in
      patients with chronic stroke.
AB  - [Purpose] The main purpose of this study was to identify the impact of rib cage
      joint mobilization and chest wall stretch on respiratory muscle tone and
      stiffness and chest expansion in stroke patients and to compare the effects of
      both interventions. [Subjects and Methods] Subjects were randomly assigned to a
      rib cage joint mobilization group (n=15) or a chest wall stretch group (n=15).
      Respiratory muscle tone and stiffness were measured using a myotonometer, and the
      chest expansion was gauged using a measuring tape. [Results] A significant
      difference was found on comparing the respiratory muscle tone and stiffness on
      the affected and sound side before intervention. Although both groups showed an
      increase in respiratory muscle tone and stiffness after intervention, no
      significant difference was found. A significant increase in chest expansion was
      observed; however, no significant difference was observed in the variations
      between the groups. [Conclusion] This study suggests that rib cage joint
      mobilization and chest wall stretch exercises can be used to increase chest
      expansion potential and respiratory muscle tone in patients with chronic stroke.

PMID- 29200635
TI  - The effects of the menstrual cycle on the static balance in healthy young women.
AB  - [Purpose] The purpose of this study was to investigate the effects of the
      menstrual cycle on the static balance of healthy young women. [Subjects and
      Methods] Eighteen healthy young subjects (mean age 19.1 years; weight 57.5 kg;
      height 159.9 cm) participated in this study. The Good Balance system was used to
      measure the postural sway speed and velocity moment of subjects in the static
      standing posture. Subjects were measured for static balance between 1 and 3 days
      after menstruation and 13 days after menstruation. [Results] The velocity moment
      of postural sway was significantly higher at 13 days after menstruation.
      [Conclusion] Our results indicate that the menstrual cycle affects the static
      balance of healthy subjects. During the menstrual cycle, intensity for balance
      exercises in females should be carefully controlled for injury prevention.

PMID- 29200636
TI  - Effect of the combination of Mendelsohn maneuver and effortful swallowing on
      aspiration in patients with dysphagia after stroke.
AB  - [Purpose] This study investigated the effect of a combined method incorporating
      the Mendelsohn maneuver and effortful swallowing on aspiration in patients with
      dysphagia after stroke. [Subjects and Methods] Three patients with dysphagia were
      recruited. All patients were treated with a combined method consisting of the
      Mendelsohn maneuver and effortful swallowing. The intervention period was total
      20 sessions. Evaluation was based on videofluoroscopic swallowing study and the
      degree of aspiration was assessed using penetration-aspiration scale. [Results]
      Before and after intervention, all participants showed a decrease in aspiration
      with liquid type and semisolid type food. [Conclusion] This study confirms that
      the combined method of the Mendelsohn maneuver and effortful swallowing has a
      positive effect on aspiration in patients with dysphagia after stroke.

PMID- 29200637
TI  - Combined respiratory muscle training facilitates expiratory muscle activity in
      stroke patients.
AB  - [Purpose] The aim of this study was to investigate the effect of combined
      respiratory muscle training on expiratory muscle activity in stroke patients.
      [Subjects and Methods] Twenty-five stroke patients were assigned to either the
      intervention group (n=12) or the control group (n=13). Both groups participated
      in a conventional stroke rehabilitation program, while the intervention group
      also received respiratory muscle training for 20 to 30 minutes a day, 3 times a
      week, for 8 weeks. Surface electromyographic data were collected from the rectus
      abdominis, internal oblique, and external oblique on the paretic side. Pulmonary
      function (forced vital capacity) and cough capacity (peak expiratory flow) also
      were measured. [Results] Both groups showed a significant increase in muscle
      activity after the intervention. However, the intervention group also showed
      significant increases in forced vital capacity and peak expiratory flow.
      Comparison of the 2 groups revealed that the intervention group had greater
      improvements in pulmonary function, cough capacity, and muscle activity.
      [Conclusion] The results of this study suggest that combined respiratory muscle
      training has positive effects on both respiratory function and expiratory muscle
      activity in stroke patients.

PMID- 29200638
TI  - Effect of neuromuscular electrical stimulation on lip strength and closure
      function in patients with dysphagia after stroke.
AB  - [Purpose] This study aimed to investigate the effect of neuromuscular electrical
      stimulation (NMES) on lip strength and closure function of patients with
      dysphagia after stroke. [Subjects and Methods] Eight patients with dysphagia were
      recruited. NMES was applied to the orbicularis oris muscle. All the participants
      received NMES for 30 min/d, 5 d/wk, for 4 weeks. Lip strength was measured using
      the Iowa Oral Performance Instrument. To assess lip closure, the lip closure
      subitem of the videofluoroscopic dysphagia scale was used. [Results] Lip strength
      showed significant improvement and lip closure function showed a significant
      decrease. [Conclusion] This study demonstrates that NMES is useful for improving
      lip strength and closure function.

PMID- 29200639
TI  - Factors influencing period from surgery to discharge in patients with femoral
      trochanteric fractures.
AB  - [Purpose] The purpose of this study was to investigate factors influencing the
      period from surgery to discharge in patients with femoral trochanteric fractures.
      [Subjects and Methods] Sixty patients with femoral trochanteric fractures were
      investigated retrospectively. Based on the mean period from surgery to discharge
      (85.6 +/- 26.6 days), the patients were divided into two groups: an under-85-day
      group (range, 29-78 days) and an over-85-day group (87-128 days). Age, gender,
      fracture type, presence of lesser trochanteric displacement, discharge
      destination, and walking ability were investigated. The relationship between
      these factors and the period from surgery to discharge was analyzed with logistic
      regression analysis. [Results] Age and lesser trochanteric displacement were
      significantly higher in the over-85-day group, and walking ability before
      fracture and at discharge were significantly lower in the over-85-day group.
      Logistic regression analysis showed that lesser trochanteric displacement and age
      were predictors of the length from surgery to discharge. Lesser trochanteric
      displacement were observed in 87.5% of these. Immediate displacement after
      surgery occurred in 57.8% of lesser trochanteric fractures, while 26.3% displaced
      1 to 3 weeks after surgery. [Conclusion] This study revealed that lesser
      trochanteric displacement, higher age, and lower walking ability before fracture
      and at discharge were associated with longer hospitalizations in patients with
      femoral trochanteric fractures. Lesser trochanteric displacement were observed in
      87.5% of lesser trochanteric fractures. These displacements occurred within 3
      weeks after surgery in 84.1% of cases.

PMID- 29200640
TI  - Audiospatial cognitive ability of visually impaired athletes in static and
      dynamic spatial cognitive tasks.
AB  - [Purpose] This study compares the orientation sense of sighted and visually
      impaired participants to provide basic research on the audiospatial cognitive
      ability of visually impaired athletes. [Subjects and Methods] Subjects included
      nine blind athletes and seven sighted subjects wearing eyeshades during static
      and dynamic tasks. In the static spatial cognitive task, a coin was dropped
      towards the right, center, or left of the subject, and the task consisted of
      identifying the location of the coin. In the dynamic spatial cognitive task,
      performed with the participant walking, an auditory stimulus was provided. In
      both spatial cognitive tasks, the independent variables consisted of the "blind
      athlete" and "sight" groups, as well as three directions; a one-way analysis of
      variance was performed with the mean error angle as a dependent variable using
      IBM SPSS Statistics. [Results] The error angles found in the rightward and
      leftward directions during the static task showed no significant differences, but
      in the dynamic task, the sight group showed a markedly greater error in the left
      side, indicating a right-and-left asymmetry in spatial cognition. [Conclusion]
      Our results suggest a highly developed skill of instantly determining the spatial
      orientation of auditory information in dynamic situations in blind athletes.

PMID- 29200641
TI  - Validity of maximal isometric knee extension strength measurements obtained via
      belt-stabilized hand-held dynamometry in healthy adults.
AB  - [Purpose] To determine the validity of knee extension muscle strength
      measurements using belt-stabilized hand-held dynamometry with and without body
      stabilization compared with the gold standard isokinetic dynamometry in healthy
      adults. [Subjects and Methods] Twenty-nine healthy adults (mean age, 21.3 years)
      were included. Study parameters involved right side measurements of maximal
      isometric knee extension strength obtained using belt-stabilized hand-held
      dynamometry with and without body stabilization and the gold standard.
      Measurements were performed in all subjects. [Results] A moderate correlation and
      fixed bias were found between measurements obtained using belt-stabilized hand
      held dynamometry with body stabilization and the gold standard. No significant
      correlation and proportional bias were found between measurements obtained using
      belt-stabilized hand-held dynamometry without body stabilization and the gold
      standard. The strength identified using belt-stabilized hand-held dynamometry
      with body stabilization may not be commensurate with the maximum strength
      individuals can generate; however, it reflects such strength. In contrast, the
      strength identified using belt-stabilized hand-held dynamometry without body
      stabilization does not reflect the maximum strength. Therefore, a chair should be
      used to stabilize the body when performing measurements of maximal isometric knee
      extension strength using belt-stabilized hand-held dynamometry in healthy adults.
      [Conclusion] Belt-stabilized hand-held dynamometry with body stabilization is
      more convenient than the gold standard in clinical settings.

PMID- 29200642
TI  - The effects of calcaneal posture on thoracolumbar alignment in a standing
      position.
AB  - [Purpose] Severe calcaneus misalignment is correlated with low back pain, and
      affects pelvic alignment. However, little has been published with regard to the
      influence of pronation and supination on trunk alignment. Therefore, the present
      study aimed to investigate the influence of calcaneal inversion on pelvic and
      trunk alignment. [Subjects and Methods] A 3-dimensional motion analysis system
      was used to assess pelvic and trunk alignment in 10 healthy male subjects with
      unilateral and bilateral calcaneus inversion. [Results] Medial and anterior
      tilting of the pelvis, and posterior tilting and lateral rotation of the trunk
      were observed. [Conclusion] Calcaneal inversion induces changes in the alignment
      of the pelvis and trunk. These changes may induce lumbar lordosis and body
      misalignment, leading to back pain.

PMID- 29200643
TI  - Comparison of the pain-relieving effects of transcutaneous electrical nerve
      stimulation applied at the same dermatome levels as the site of pain in the wrist
      joint.
AB  - [Purpose] The purpose of this study was to develop a proposal for an effective
      interventional option for therapeutic stimulation sites by comparing the pain
      relieving effect of transcutaneous electrical nerve stimulation (TENS) applied to
      the same dermatome level of the contralateral sites of the dorsal wrist joint
      with the pain or the neck, or both sites simultaneously. [Subjects and Methods] A
      control was first established by triggering pain in the left dorsal wrist joints
      of adult females by using heat stimulation. Three interventions were then
      performed, comprising the TENS to the contralateral wrist joint (CW) and to the
      neck (N) at the same dermatome level as the site of pain, and the TENS to both CW
      and N simultaneously (CWN). Levels of pain and cerebral blood flow were also
      measured. [Results] The pain levels of three interventions were found to be
      significantly decreased compared with the control; however, no significant
      differences in the levels of pain were seen between any combinations of three
      interventions. Furthermore, no significant differences were seen between any
      interventions in terms of cerebral blood flow. [Conclusion] The results suggest
      that in order for TENS to be effective, it is necessary to make effective use of
      the dermatome.

PMID- 29200644
TI  - Analysis of the relationships among perceived service encounter quality, service
      value, satisfaction and behavioral intention for physical therapy patients.
AB  - [Purpose] The purpose of this study was to investigate the relationships among
      perceived service encounter quality, service value, patient satisfaction, and
      behavioral intention in physical therapy patients. [Subjects and Methods] This
      study surveyed 335 patients who received physical therapy treatment at five
      medical institutions in Jeonju-si, Republic of Korea. This study conducted path
      analysis on the collected data using Smart PLS 2.0 M3. [Results] The analysis of
      this study showed that service encounter quality had significantly positive
      relationship with service value, patient satisfaction, and behavioral intention.
      Service value had significantly positive relationship with patient satisfaction
      and behavioral intention. Patient satisfaction had significantly positive
      relationship with behavioral intention. [Conclusion] Improving the perceived
      quality of service encounters for physical therapy patients increases service
      value and patient satisfaction, and positively influences behavioral intention.

PMID- 29200645
TI  - Changes in fatigue and physical function with age for patients with
      gastrointestinal cancer in the perioperative period: a comparison between older
      and young patients.
AB  - [Purpose] The purpose of this study was to examine changes in fatigue and
      physical function with age for groups of patients with gastrointestinal cancer in
      the perioperative period. [Subjects and Methods] The study involved 52 patients
      with gastrointestinal cancer (28 males and 24 females, aged 62.4 +/- 12.0 years).
      The subjects were divided into two groups: those 65 or over (the so-called
      elderly group,) and those 64 or under (the so-called young group). The six minute
      walk distance (6MWD), Cancer Fatigue Scale (CFS), and serum albumin (ALB) were
      evaluated on three occasions: before surgery, after surgery and after discharge.
      This study considered change in physical function and fatigue, differences
      between the two groups and correlations between age and each evaluation on the
      three occasions. [Results] The 6MWD was the main difference between the elderly
      and young groups, with the former having significantly reduced 6MWD values as
      compared to the latter after surgery. Age was positively correlated with 6MWD and
      ALB after surgery and after discharge. Moreover, age was negatively correlated
      with CFS after surgery and after discharge. [Conclusion] It is suggested that
      elderly patients are more likely to experience a decline in exercise tolerance
      and an increase in fatigue.

PMID- 29200646
TI  - Effect of pain on fear of falling in patients with femoral proximal fracture.
AB  - [Purpose] This study investigated the factors affecting fear of falling in
      patients with femoral proximal fracture. [Subjects and Methods] The participants
      were 26 patients with femoral proximal fracture (3 males and 23 females, average
      age: 80.2 +/- 7.9 years). Fall self-efficacy, motor functions, and pain intensity
      were measured 4 weeks post-surgery, and the participants were divided into three
      groups based on their scores on the Falls Efficacy Scale. [Results] The group
      with low fall self-efficacy was significantly older and experienced stronger pain
      than the group with high fall self-efficacy did. In a multivariate analysis, age
      and pain intensity were extracted as factors influencing fall self-efficacy.
      [Conclusion] For patients with femoral proximal fracture, in addition to age,
      pain was identified as a correlated factor to fear of falling.

PMID- 29200647
TI  - Estimation of 1RM for knee extension based on the maximal isometric muscle
      strength and body composition.
AB  - [Purpose] To create a regression formula in order to estimate 1RM for knee
      extensors, based on the maximal isometric muscle strength measured using a hand
      held dynamometer and data regarding the body composition. [Subjects and Methods]
      Measurement was performed in 21 healthy males in their twenties to thirties.
      Single regression analysis was performed, with measurement values representing
      1RM and the maximal isometric muscle strength as dependent and independent
      variables, respectively. Furthermore, multiple regression analysis was performed,
      with data regarding the body composition incorporated as another independent
      variable, in addition to the maximal isometric muscle strength. [Results] Through
      single regression analysis with the maximal isometric muscle strength as an
      independent variable, the following regression formula was created: 1RM
      (kg)=0.714 + 0.783 * maximal isometric muscle strength (kgf). On multiple
      regression analysis, only the total muscle mass was extracted. [Conclusion] A
      highly accurate regression formula to estimate 1RM was created based on both the
      maximal isometric muscle strength and body composition. Using a hand-held
      dynamometer and body composition analyzer, it was possible to measure these items
      in a short time, and obtain clinically useful results.

PMID- 29200648
TI  - The immediate effects of proprioceptive neuromuscular facilitation with taping on
      gait parameters in patients with chronic stroke.
AB  - [Purpose] The purpose of the present study was to examine the immediate effects
      of simultaneous application of proprioceptive neuromuscular facilitation (PNF)
      and elastic taping (T), and the removal of the elastic tape, on the gait
      parameters of stroke patients. [Subjects and Methods] Twenty stroke patients were
      divided into a proprioceptive neuromuscular facilitation group (PNFG, n=7), a
      taping group (TG, n=6), and a proprioceptive neuromuscular facilitation with
      taping group (PNFTG, n=7). Relevant interventions were applied for 30 minutes,
      the tape was removed, and gait parameters were evaluated. [Results] Only the
      intervention of the PNFTG yielded significant differences in patient cadence,
      speed, and stride length. [Conclusion] The simultaneous application of PNF and
      taping for 30 minutes has carryover effects that can improve stroke patients'
      gait ability, even after the removal of the tape.

PMID- 29200649
TI  - The effects of whole body vibration combined biofeedback postural control
      training on the balance ability and gait ability in stroke patients.
AB  - [Purpose] The purpose of this study was to examine the effect of biofeedback
      postural control training using whole body vibration in acute stroke patients on
      balance and gait ability. [Subjects and Methods] Thirty stroke patients
      participated in this study and were divided into a group of 10, a group for
      biofeedback postural control training combined with a whole body vibration, one
      for biofeedback postural control training combined with an aero-step, and one for
      biofeedback postural control training. Biorescue was used to measure the limits
      of stability, balance ability, and Lukotronic was used to measure step length,
      gait ability. [Results] In the comparison of balance ability and gait ability
      between the groups for before and after intervention, Group I showed a
      significant difference in balance ability and gait ability compared to Groups II
      and III. [Conclusion] This study showed that biofeedback postural control
      training using whole body vibration is effective for improving balance ability
      and gait ability in stroke patients.

PMID- 29200651
TI  - Effects of taping and proprioceptive neuromuscular facilitation for stance phase
      duration of stroke patients.
AB  - [Purpose] The purpose of this study was to investigate the effects of taping and
      proprioceptive neuromuscular facilitation in stroke patients. [Subjects and
      Methods] Thirty patients who were diagnosed with hemiparalysis due to stroke were
      selected as subjects of study. Experiment group 1 patients had Kinesio taping
      applied before applying the PNF, while experiment group 2 patients had McConell
      taping applied before applying the PNF. The control group had only the PNF
      applied. The dartfish program was used to evaluate the stance phase of stroke
      patients. [Results] Experiment group 1 and experiment group 2 showed a
      significantly longer stance phase duration of the affected side than the control
      group in week 6. [Conclusion] Application of Kinesio taping has a more positive
      effect on the stance phase duration than McConell taping in the patients with
      stroke.

PMID- 29200650
TI  - Anteroposterior perception of the trunk position while seated without the feet
      touching the floor.
AB  - [Purpose] The purpose of this study was to investigate the trunk position
      perception in the anteroposterior direction in young participants sitting without
      their feet touching the floor to avoid the influence of the hamstrings tension
      and the feet pressure on the perception. [Subjects and Methods] Fourteen healthy
      volunteers were seated on a chair fitted with an original manual goniometer.
      There were 7 reference positions set at 5 degrees  increments, from -15 degrees 
      to 15 degrees , and reproductions of each position were conducted 5 times. Trunk
      position perception was evaluated by the absolute error between the reproduced
      trunk angle and the reference position angle. [Results] The results revealed a
      significant effect of reference position on the absolute error. The absolute
      error at the -5 degrees  reference position was significantly larger than at the 
      15 degrees  and 15 degrees  positions, and the absolute error at the 0 degrees 
      position was significantly larger than at the -15 degrees , 10 degrees , and 15
      degrees  positions. [Conclusion] These results suggest that the perception of
      extreme forward- and backward-leaning trunk positions while sitting without the
      feet touching the floor would be higher than in a neutral sitting position. The
      relationship between the stability of the posture and the perception may be
      involved in the sitting position.

PMID- 29200652
TI  - Changes in the amount of physical activity in minimally invasive cardiac surgery.
AB  - [Purpose] This study aimed to compare the amount of physical activity in a
      minimally invasive cardiac surgery (MICS) group with that in a conventional
      surgery (median sternotomy) group. [Subjects and Methods] Between November 2010
      and December 2011, 39 consecutive patients who underwent elective surgery for
      valvular disease were prospectively enrolled. The amount of physical activity
      before and after surgery was measured in 22 cases. The daily in-hospital physical
      activity level was measured continuously using a triaxial accelerometer. The
      results were compared in terms of change in the amount of physical activity pre-
      and postoperatively. [Results] There was no significant difference between the
      two groups in the amount of physical activity before surgery. However, the amount
      of physical activity after surgery was significantly higher in the MICS group
      compared with the conventional surgery group. The number of steps after surgery
      was significantly increased in the MICS group, and the rate of change in the
      amount of physical activity was significantly higher in the MICS group than that
      in the conventional surgery group. [Conclusion] The MICS approach is associated
      with improvement in postoperative physical activity over median sternotomy.

PMID- 29200653
TI  - Research describing pelvifemoral rhythm: a systematic review.
AB  - [Purpose] This systematics review was undertaken to synthesize what is known
      regarding pelvifemoral rhythm, that is, the coordinated flexion of the thigh and
      posterior tilting of the pelvis during hip flexion (HF). [Methods] Three
      databases were searched. [Results] Nine relevant articles were identified via
      independent database searches and a hand search by the authors. The articles were
      consistent in showing that pelvifemoral rhythm underlies the HF motion under
      conditions as varied as passive unilateral flexion while supine and active
      bilateral flexion while hanging from a bar. Posterior pelvic tilting, which
      begins early during HF, contributes between 13.1% to 37.5% of total HF. Pelvic
      tilting and HF excursions are highly correlated (r=0.89 to 1.00). [Conclusions]
      Pelvifemoral rhythm is present to varying degrees during hip flexion under
      diverse conditions.

PMID- 29200654
TI  - Scoliosis deformity reduction in adults: a CBP(r) Mirror Image(r) case series
      incorporating the 'non-commutative property of finite rotation angles under
      addition' in five patients with lumbar and thoraco-lumbar scoliosis.
AB  - [Purpose] This case series presents the unique application of the non-commutative
      property of finite rotation angles under addition to the CBP(r) mirror image(r)
      treatment protocol for adult lumbar and thoraco-lumbar scoliosis. [Subjects and
      Methods] Five adult patients having lumbar/thoraco-lumbar scoliosis and back
      pain, and having at least two prominent thoracic postural abnormalities according
      to Harrison's rotations and translations of thoracic postures were included.
      After initial assessment, mirror-image stress x-rays were taken. For each
      patient, one stress film was taken using the order of mirror image movements with
      the largest displacement followed by the second largest (primary + secondary) and
      one stress film was taken in the opposite order (secondary + primary). The
      consecutive ordered movements that resulted in the largest reduction of curvature
      were chosen as the order-specific series of movements all exercises and postural
      traction were to be performed for each patient. Spinal manipulation was also
      performed. [Results] All patients had a reduction of curvature concomitant with a
      reduction in pain levels. [Conclusion] This unique treatment approach offers a
      patient-specific, targeted structural rehabilitative procedure to stress the
      spine towards a more straightened configuration. Adult lumbar and thoraco-lumbar
      curves can be reduced and improved by these non-invasive CBP methods.

PMID- 29200655
TI  - Lumbar extension traction alleviates symptoms and facilitates healing of disc
      herniation/sequestration in 6-weeks, following failed treatment from three
      previous chiropractors: a CBP(r) case report with an 8 year follow-up.
AB  - [Purpose] To present the outcome of a patient, having sciatica and MRI-verified
      disc herniation/sequestration who underwent Chiropractic BioPhysics(r) (CBP(r))
      protocol designed to improve the lumbar lordosis. [Subject and Methods] A 56-year
      old male suffered from chronic low back pain and recent sciatica due to lumbar
      disc herniation despite being under continuous care from three previous
      chiropractors. Radiographic analysis revealed a lumbar hypolordosis and MRI
      confirmed disc herniation and sequestration at L4-L5. Generalized decreased
      lumbar range of motion and multiple positive orthopedic and neurologic tests were
      present. [Results] After 26 treatments of CBP lumbar extension traction over 9
      weeks a total reduction of the disc herniation and sequestration occurred with
      concomitant improvement in neurologic symptoms. Continuing maintenance
      treatments, an 8 year follow-up shows no relapse of condition and patient
      remained in good health. [Conclusion] A patient with lumbar disc
      herniation/sequestration was successfully treated with CBP technique procedures
      including lumbar extension traction that achieved a significant healing of
      herniation and significant reduction in symptoms not obtained following
      traditional chiropractic procedures alone. The quick reduction in lumbar disc
      herniation would appear to be related to a segmental disc unloading force
      produced during extension traction procedures for increasing the lumbar
      curvature.

PMID- 29200656
TI  - Nonsurgical correction of straight back syndrome (thoracic hypokyphosis),
      increased lung capacity and resolution of exertional dyspnea by thoracic
      hyperkyphosis mirror image(r) traction: a CBP(r) case report.
AB  - [Purpose] To present the increase in thoracic kyphosis in a patient suffering
      from exertional dyspnea, reduced lung capacity, and spinal pains related to
      straight back syndrome (SBS). [Subject and Methods] A 33-year-old male patient
      was put on a CBP(r) corrective care program involving mirror image(r) traction
      procedures designed to increase the thoracic kyphosis. [Results] This patient had
      a 10 degrees  improvement in thoracic kyphosis in 16-weeks that was maintained 7
      months later. There was a simultaneous reduction of pain, resolved exertional
      dyspnea, and a greater than 2 liter increase in lung capacity. [Conclusion] This
      case illustrates that nonsurgical improvement in thoracic kyphosis in a patient
      with SBS is possible and that this may positively influence lung capacity, health
      and function.

PMID- 29200657
TI  - Reduction of progressive thoracolumbar adolescent idiopathic scoliosis by
      chiropractic biophysics(r) (CBP(r)) mirror image(r) methods following failed
      traditional chiropractic treatment: a case report.
AB  - [Purpose] To present a case demonstrating the reduction of progressive
      thoracolumbar scoliosis by incorporating Chiropractic BioPhysics(r) (CBP(r))
      technique's mirror image(r) exercises, traction and blocking procedures based on
      the 'non-commutative properties of finite rotation angles under addition'
      engineering law. [Subject and Methods] A 15-year-old female presented with a
      right thoracolumbar scoliosis having a Cobb angle from T5-L3 of 27 degrees  and
      suffering from headaches and lower back pains. Her curve had progressed over the
      last two years despite being under traditional chiropractic care. [Results] The
      patient was treated using CBP structural rehabilitation protocols incorporating
      mirror image traction, home blocking, corrective exercises and spinal
      manipulation. The patient was treated 24 times (including 45 home self-treatment
      blocking sessions) over the course of 15-weeks. Her thoracolumbar curve reduced
      from 27 degrees  to 8 degrees  and her headache and low back pain disability
      improved significantly. [Conclusion] CBP mirror image exercises and traction are
      consistent with other successful non-surgical approaches and show promise in
      treating adolescent idiopathic scoliosis.

PMID- 29200658
TI  - Size and shape distributions of primary crystallites in titania aggregates.
AB  - The primary crystallite size of titania powder relates to its properties in a
      number of applications. Transmission electron microscopy was used in this
      interlaboratory comparison (ILC) to measure primary crystallite size and shape
      distributions for a commercial aggregated titania powder. Data of four size
      descriptors and two shape descriptors were evaluated across nine laboratories.
      Data repeatability and reproducibility was evaluated by analysis of variance. One
      third of the laboratory pairs had similar size descriptor data, but 83% of the
      pairs had similar aspect ratio data. Scale descriptor distributions were
      generally unimodal and were well-described by lognormal reference models. Shape
      descriptor distributions were multi-modal but data visualization plots
      demonstrated that the Weibull distribution was preferred to the normal
      distribution. For the equivalent circular diameter size descriptor, measurement
      uncertainties of the lognormal distribution scale and width parameters were 9.5%
      and 22%, respectively. For the aspect ratio shape descriptor, the measurement
      uncertainties of the Weibull distribution scale and width parameters were 7.0%
      and 26%, respectively. Both measurement uncertainty estimates and data
      visualizations should be used to analyze size and shape distributions of
      particles on the nanoscale.

PMID- 29200659
TI  - Electrochemical detection of urinary microRNAs via sulfonamide-bound antisense
      hybridisation.
AB  - Altered serum and plasma microRNA (miRNA) expression profiles have been observed
      in numerous human diseases, with a number of studies describing circulating miRNA
      biomarkers for cancer diagnosis, prognosis and response to treatment, and
      recruitment to clinical trials for miRNA-based drug therapy already underway.
      Electrochemical detection of biomarkers in urine has several significant
      advantages over circulating biomarker analysis including safety, cost, speed and
      ease of conversion to the point of care environment. Consequently, much current
      research is underway to identify urinary miRNA biomarkers for a variety of
      pathologies including prostate and bladder malignancies, and renal disorders. We
      describe here a robust method capable of electrochemical detection of human
      urinary miRNAs at femtomolar concentrations using a complementary DNA-modified
      glassy carbon electrode. A miR-21-specific DNA hybridisation probe was
      immobilised onto a glassy carbon electrode modified by sulfonic acid deposition
      and subsequent chlorination. In our pilot system, the presence of synthetic
      mature miR-21 oligonucleotides increased resistance at the probe surface to
      electron transfer from the ferricyanide/ferrocyanide electrolyte. Response was
      linear for 10 nM-10 fM miR-21, with a limit of detection of 20 fM, and detection
      discriminated between miR-21, three point-mutated miR-21 sequences, and miR-16.
      We then demonstrated similar sensitivity and reproducibility of miR-21 detection
      in urine samples from 5 human control subjects. Our protocol provides a platform
      for future high-throughput screening of miRNA biomarkers in liquid biopsies.

PMID- 29200660
TI  - Measuring Ultra-low Levels of Nucleotide Biomarkers Using Quartz Crystal
      Microbalance and SPR Microarray Imaging Methods: A Comparative Analysis.
AB  - Circulating serum nucleotide biomarkers are useful indicators for early diagnosis
      of cancer, respiratory illnesses, and other deadly diseases. In this work, we
      compared detection performances of a quartz crystal microbalance (QCM), which is
      a mass sensor, with that of a surface plasmon resonance (SPR) microarray for an
      oligonucleotide mimic of a microRNA-21 biomarker. A surface immobilized capture
      oligonucleotide probe was used to hybridize with the target oligonucleotide
      (i.e., the microRNA-21 mimic) to facilitate selective detection. To obtain ultra
      low femtomolar (fM) detection sensitivity, gold nanoparticles (50 nm) were
      conjugated with the target oligonucleotide. We achieved detection limits of 28and
      47 fM for the target oligonucleotide by the QCM and SPRi microarray,
      respectively. We also conducted sample recovery studies and performed matrix
      effect analysis. Although the QCM had a lower detection limit, the microarray
      approach offered better throughput for analysis of up to 16 samples. We confirmed
      that the designed assay was selective for the target oligonucleotide and did not
      show signals for the control oligonucleotide with five mismatch sites relative to
      the target sequence. Combination of the QCM and microarray methods that utilize
      the same assay chemistry on gold are useful for overcoming clinical sample matrix
      effects and achieving ultra-low detection of small nucleotide biomarkers with
      quantitative insights.

PMID- 29200662
TI  - Gearing effects of the patella (knee extensor muscle sesamoid) of the helmeted
      guineafowl during terrestrial locomotion.
AB  - Human patellae (kneecaps) are thought to act as gears, altering the mechanical
      advantage of knee extensor muscles during running. Similar sesamoids have evolved
      in the knee extensor tendon independently in birds, but it is unknown if these
      also affect the mechanical advantage of knee extensors. Here, we examine the
      mechanics of the patellofemoral joint in the helmeted guineafowl Numida meleagris
      using a method based on muscle and tendon moment arms taken about the patella's
      rotation centre around the distal femur. Moment arms were estimated from a
      computer model representing hindlimb anatomy, using hip, knee and patellar
      kinematics acquired via marker-based biplanar fluoroscopy from a subject running
      at 1.6 ms-1 on a treadmill. Our results support the inference that the patella of
      Numida does alter knee extensor leverage during running, but with a mechanical
      advantage generally greater than that seen in humans, implying relatively greater
      extension force but relatively lesser extension velocity.

PMID- 29200663
TI  - In search of standards to support circularity in product policies: A systematic
      approach.
AB  - The aspiration of a circular economy is to shift material flows toward a zero
      waste and pollution production system. The process of shifting to a circular
      economy has been initiated by the European Commission in their action plan for
      the circular economy. The EU Ecodesign Directive is a key policy in this
      transition. However, to date the focus of access to market requirements on
      products has primarily been upon energy efficiency. The absence of adequate
      metrics and standards has been a key barrier to the inclusion of resource
      efficiency requirements. This paper proposes a framework to boost sustainable
      engineering and resource use by systematically identifying standardization needs
      and features. Standards can then support the setting of appropriate material
      efficiency requirements in EU product policy. Three high-level policy goals
      concerning material efficiency of products were identified: embodied impact
      reduction, lifetime extension and residual waste reduction. Through a lifecycle
      perspective, a matrix of interactions among material efficiency topics (recycled
      content, re-used content, relevant material content, durability, upgradability,
      reparability, re-manufacturability, reusability, recyclability, recoverability,
      relevant material separability) and policy goals was created. The framework was
      tested on case studies for electronic displays and washing machines. For
      potential material efficiency requirements, specific standardization needs were
      identified, such as adequate metrics for performance measurements, reliable and
      repeatable tests, and calculation procedures. The proposed novel framework aims
      to provide a method by which to identify key material efficiency considerations
      within the policy context, and to map out the generic and product-specific
      standardisation needs to support ecodesign. Via such an approach, many different
      stakeholders (industry, academics, policy makers, non-governmental organizations
      etc.) can be involved in material efficiency standards and regulations.
      Requirements and standards concerning material efficiency would compel product
      manufacturers, but also help designers and interested parties in addressing the
      sustainable resource use issue.

PMID- 29200664
TI  - Proportions of Proinflammatory Monocytes Are Important Predictors of Mortality
      Risk in Hemodialysis Patients.
AB  - Despite the continuous progression in dialysis medicine, mortality and the burden
      of cardiovascular disease (CVD) among hemodialysis patients are still
      substantial. Substantial evidence suggests that proinflammatory (CD16+) monocytes
      contribute to the development of atherosclerosis. A cohort of 136 stable
      hemodialysis patients (follow-up: 6.25 year) was assessed to investigate the
      association between the proportion of CD16+ monocytes for all-cause and CVD
      mortalities. The CD16+ monocytes were associated with both mortalities after
      adjusting for a preexisting CVD history. Compared to the reference group (CD16+
      monocytes within [15.6-18.6], the first and second quartile), patients with CD16+
      monocytes above the highest quartile level (>21.5) had an adjusted hazard ratio
      (HR) of 30.85 (95% confidence interval [CI]: 7.12-133.8) for CVD mortality and
      5.28 (2.07-13.49) for all-cause mortality, and those with CD16+ monocytes below
      the lowest quartile <=15.6), had significantly elevated death risks after 3.5
      year follow-up (HR [95% CI]: 10.9 [2.42-48.96] and 4.38 [1.45-13.24] for CV and
      all-cause mortalities, respectively). The hemodialysis patients with CD16+
      monocyte level in a low but mostly covering normal range also portended a poor
      prognosis. The findings shed some light for nephrologists on future prospects of
      early recognizing immune dysfunction and improving early intervention outcomes.

PMID- 29200661
TI  - Spatially and Temporally Controlled Hydrogels for Tissue Engineering.
AB  - Recent years have seen tremendous advances in the field of hydrogel-based
      biomaterials. One of the most prominent revolutions in this field has been the
      integration of elements or techniques that enable spatial and temporal control
      over hydrogels' properties and functions. Here, we critically review the emerging
      progress of spatiotemporal control over biomaterial properties towards the
      development of functional engineered tissue constructs. Specifically, we will
      highlight the main advances in the spatial control of biomaterials, such as
      surface modification, microfabrication, photo-patterning, and three-dimensional
      (3D) bioprinting, as well as advances in the temporal control of biomaterials,
      such as controlled release of molecules, photocleaving of proteins, and
      controlled hydrogel degradation. We believe that the development and integration
      of these techniques will drive the engineering of next-generation engineered
      tissues.

PMID- 29200666
TI  - Prevention of Memory Impairment and Neurotrophic Factors Increased by Lithium in
      Wistar Rats Submitted to Pneumococcal Meningitis Model.
AB  - The aim of this study was to investigate the effects of lithium on brain-derived
      neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line
      derived neurotrophic factor (GDNF) expression in the hippocampus and on memory in
      experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a
      neuroprotective agent with many effects on the brain. In this study, animals
      received either artificial cerebrospinal fluid or Streptococcus pneumoniae
      suspension at a concentration of 5 * 109 CFU/mL. Eighteen hours after induction,
      all animals received ceftriaxone. The animals received saline or lithium (47.5
      mg/kg) or tamoxifen (1 mg/kg) as adjuvant treatment, and they were separated into
      six groups: control/saline, control/lithium, control/tamoxifen,
      meningitis/saline, meningitis/lithium, and meningitis/tamoxifen. Ten days after
      meningitis induction, animals were subjected to open-field habituation and the
      step-down inhibitory avoidance tasks. Immediately after these tasks, the animals
      were killed and their hippocampus was removed to evaluate the expression of BDNF,
      NGF, and GDNF. In the meningitis group, treatment with lithium and tamoxifen
      resulted in improvement in memory. Meningitis group showed decreased expression
      of BDNF and GDNF in the hippocampus while lithium reestablished the neurotrophin
      expression. Lithium was able to prevent memory impairment and reestablishes
      hippocampal neurotrophin expression in experimental pneumococcal meningitis.

PMID- 29200667
TI  - Davallia mariesii Moore Improves FcepsilonRI-Mediated Allergic Responses in the
      Rat Basophilic Leukemia Mast Cell Line RBL-2H3 and Passive Cutaneous Anaphylaxis
      in Mice.
AB  - Davallia mariesii Moore (Drynaria rhizome extract (DRE)) is widely known for its
      efficacy in treating inflammation, arteriosclerosis, and bone injuries. This
      study evaluated whether treatment with DRE inhibited FcERI-mediated allergic
      responses in the RBL-2H3 mast cells and investigated the early- and late-phase
      mechanisms by which DRE exerts its antiallergic effects. IgE anti-DNP/DNP-HSA
      sensitized RBL-2H3 mast cells were tested for cytotoxicity to DRE, followed by
      the assessment of beta-hexosaminidase release. We measured the amounts of
      inflammatory mediators (e.g., histamine, PGD2, TNF-alpha, IL-4, and IL-6) and
      examined the expression of genes involved in arachidonate and FcepsilonRI
      signaling pathways. In addition, we confirmed the antiallergic effects of DRE on
      passive cutaneous anaphylaxis (PCA) in mice. DRE inhibited RBL-2H3 mast cell
      degranulation and production of allergic mediators in them. In early allergic
      responses, DRE reduced expression of FcepsilonRI signaling-related genes (e.g.,
      Syk, Lyn, and Fyn) and extracellular signal-regulated kinase phosphorylation in
      mast cells. In late allergic responses, DRE reduced PGD2 release and COX-2
      expression and cPLA2 phosphorylation in FcERI-mediated mast cells. Lastly, 250
      500 mg/kg DRE significantly attenuated the IgE-induced PCA reaction in mice.
      These findings provide novel information on the molecular mechanisms underlying
      the antiallergic effects of DRE in FcERI-mediated allergic responses.

PMID- 29200665
TI  - The Role of High-Mobility Group Box-1 and Its Crosstalk with Microbiome in
      Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, definitely disabling, and potentially
      severe autoimmune disease. Although an increasing number of patients are
      affected, a key treatment for all patients has not been discovered. High-mobility
      group box-1 (HMGB1) is a nuclear protein passively and actively released by
      almost all cell types after several stimuli. HMGB1 is involved in RA
      pathogenesis, but a convincing explanation about its role and possible modulation
      in RA is still lacking. Microbiome and its homeostasis are altered in patients
      with RA, and the microbiota restoration has been proposed to patients with RA.
      The purpose of the present review is to analyze the available evidences regarding
      HMGB1 and microbiome roles in RA and the possible implications of the crosstalk
      between the nuclear protein and microbiome in understanding and possibly treating
      patients affected by this harmful condition.

PMID- 29200668
TI  - A Study of Clinical Profile of Primary Extranodal Lymphomas in a Tertiary Care
      Institute in South India.
AB  - Context: Primary extranodal lymphoma (pENL) refers to group of disorders arising
      from tissues other than lymph nodes. The incidence of pENL is increasing and is
      probably due to better diagnostic immunophenotyping and imaging modalities.
      Hence, this study was undertaken to ascertain the incidence, distribution, and
      histological subtypes of extranodal non-Hodgkin lymphoma (NHL) in a tertiary care
      institute in South India. Subjects and Methods: This was a retrospective study of
      patients diagnosed to have histologically proven NHL. The demographic and
      clinical features, laboratory parameters, imaging findings, histopathology, and
      immunophenotyping were documented. The lymphomas were grouped as extranodal and
      nodal. The data were tabulated in a Microsoft Excel sheet, and descriptive
      analysis was done. Results: Primary extranodal NHLs constituted 35.96% (41/114)
      of all NHLs. The B symptoms were less common in pENL compared to nodal NHL.
      Gastrointestinal tract (GIT) constituted the most common extranodal site (19/41,
      46.34%), and diffuse large B-cell lymphoma (DLBCL) was the most common
      histological subtype. Majority (40/41, 97%) of the patients with pENL were
      immunocompetent. 31/41 (75%) patients were in Stage I-II compared to 58/73
      (79.4%) patients in Stage III-IV in nodal NHL. Conclusions: Primary extranodal
      NHL constituted about one-third of patients diagnosed to have NHL at our center
      with the GIT being the most common site of presentation and DLBCL being the most
      common histology. A strong suspicion of NHL at an extranodal site with
      appropriate pathological and immunophenotyping evidence is needed to establish
      the diagnosis of a pENL.

PMID- 29200669
TI  - Adrenal Mass: Unusual Presentation and Outcome.
AB  - Aim: Adrenal mass may be functioning or nonfunctioning with varied clinical
      presentations. This study aimed to report the nature and management of uncommon
      adrenal mass and to review literature. Materials and Methods: This was an
      retrospective observational analysis of children with uncommon adrenal mass
      admitted during 2009-2015. Clinical features, investigations, and management of
      patients were analyzed. Results: Among six, two each were adolescent and neonate,
      and one each was young infant and prenatal. Clinical presentation was variable;
      hypertensive retinopathy,[1] virilization[1] and bleeding diathesis,[1] antenatal
      suprarenal mass,[1] prenatal adrenal angiolipoma,[1] and spontaneous resolution
      of Stage III suprarenal mass.[1] Ultrasound and contrast-enhanced computed
      tomography revealed well-defined, heterogeneous adrenal mass. Size varied from 2
      to 15 cm. Urinary metanephrine and serum testosterone were raised in adolescent
      hypertensive boys and virilized girls, respectively. Laparoscopy-assisted
      adrenalectomy was done in two and other four were managed conservatively.
      Histopathology of tumor revealed pheochromocytoma and borderline oncocytoma.
      Spontaneous resolution of adrenal mass had varied etiology; adrenal hemorrhagic
      lesion,[1] simple cyst,[1] neuroblastoma.[1] Follow-up varied from 3 months to 2
      years. All patients were asymptomatic on last follow-up. Conclusion: Close
      clinical follow-up, contrast-enhanced tomography, and limited/specific endocrine
      work-up have definite role in the management of uncommon adrenal mass.

PMID- 29200670
TI  - Clinico-radiological and Pathological Characteristics of Inflammatory
      Myofibroblastic Tumors in Children: A Retrospective Study.
AB  - Purpose: Inflammatory myofibroblastic tumors (IMTs) are rare, benign lesions most
      often seen in the lung of young adults but can occur in children, in various
      sites. They mimic, clinically and radiologically, malignant tumors - especially
      sarcomas and lymphomas. The aim was to review the clinical, radiological, and
      pathological data of children with a diagnosis of IMT referred to our department.
      Materials and Methods: This retrospective study was conducted at the Department
      of Medical and Paediatric Oncology, Regional Cancer Centre, Sher-I-Kashmir
      Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India from January
      2014 to December 2015. Results: Among 288 pediatric tumors registered during the
      study, 5 (1.73%) had the diagnosis of IMTs. The main symptoms were abdominal
      distension and pain in 60% (three cases), breathlessness and cough in 20% (one
      case), and right axillary area swelling in 20% (one case). In three patients,
      complete surgical excision was done, whereas another patient with retroperitoneal
      mass had the residual disease and received chemotherapy followed by complete
      second surgery. In the case of mediastinal IMT, surgery was followed by local
      radiotherapy. At present, four patients are disease-free and one patient with
      mediastinal IMT has the residual progressive disease. Conclusion: On
      presentation, IMT can constitute a formidable challenge, from diagnosis through
      to treatment.

PMID- 29200671
TI  - Multiplex Approach in Classification, Diagnosis, and Prognostication in Acute
      Myeloid Leukemia: An Experience from Tertiary Cancer Center in South India.
AB  - Introduction: Acute myeloid leukemia (AML) is a heterogeneous group of disorders
      classified as per FAB subtypes and more recently by WHO by underlying genetic
      abnormalities. Aims and Objectives: This study aims to analyze the morphology,
      immunophenotype, cytogenetic and molecular abnormalities in around 200 patients
      of AML diagnosed over a period of 7 years at our institute and to determine
      relative frequency of various subtypes (based on FAB and WHO classification). An
      attempt to characterize the associations between hematological parameters,
      immunophenotype and these subtypes was also made. Materials and Methods: All
      cases diagnosed as AML on morphology, cytochemistry and/or immunophenotyping and
      tested for recurrent genetic abnormalities during period of Jan 2008-July 2014
      were included in the study. Results: Age of presentation was younger in our AML
      patients as compared to western literature. Amongst FAB and WHO subtypes, M2 and
      t (15;17) PML-RARA were the most common groups respectively. As expected, CD33,
      CD13, were the most commonly expressed markers followed by HLA-DR, CD117, CD34
      and CD14. Aberrant expression was seen in 62(41.6%) cases, most common was CD7
      (15.4%), followed by CD56 (14.8%), CD19 (6.7%) and CD2 (4.7%). Significant
      associations between immunophenotypic markers and FAB subtypes as well as WHO
      subtypes were established. Conclusion: This is a hospital based study, giving a
      detailed account of frequencies of AML subtypes, hematological parameters and
      immunophenotypic markers in AML patients at our institute. Being a large and one
      of its kind study to establish significant associations between various
      haematological and immunophenotypic parameters with respective AML subtypes and
      genetic abnormalities, it might prove to be very useful in Indian setup where
      facilities for cytogenetic analysis are not available in many laboratories.

PMID- 29200672
TI  - Evaluation of Micronucleus in Exfoliated Buccal Epithelial Cells Using Liquid
      based Cytology Preparation in Petrol Station Workers.
AB  - Background: Liquid-based cytology (LBC) can be used for the evaluation of
      micronucleus (MN) in exfoliated buccal epithelial cells of populations
      occupationally exposed to potentially carcinogenic agents. Aim: This study was
      undertaken to evaluate the frequency of MN of exfoliated buccal epithelial cells
      using LBC preparation in petrol station workers. Materials and Methods: Fifty
      petrol station workers (cases) and fifty hospital administrative staffs
      (controls) were recruited and evaluated for MN by May-Grunwald Giemsa,
      Hematoxylin and Eosin, and Papanicolaou stains using LBC preparation. Statistical
      analysis was performed with Student's t-test, and P < 0.05 was considered
      statistically significant. Results: Regardless of staining method used, the mean
      frequency of MN for cases was significantly higher than that of controls (P <
      0.001). Conclusion: The present study concluded that petrol station workers are
      under risk of significant cytogenetic damage. The MN in exfoliated buccal
      epithelial cells found to be a useful biomarker of occupational exposure to
      genotoxic chemicals. LBC can be used for sample preparation to evaluate the
      frequency of MN in those who are occupationally exposed to potentially
      carcinogenic agents in view of overall improvement on sample preservation and
      visualization of cell morphology.

PMID- 29200674
TI  - Effectiveness of Three Prognostic Scoring Systems in Predicting the Response and
      Outcome in Pediatric Chronic Myeloid Leukemia Chronic Phase on Frontline
      Imatinib.
AB  - Introduction: The Sokal and Hasford (Euro) scores were developed in the
      chemotherapy and interferon eras and are widely used as prognostic indicators in
      patients with chronic myeloid leukemia (CML). Recently, European Treatment and
      Outcome Study (EUTOS) scoring system was introduced. Data on risk stratification
      in pediatric CML population was lacking due to its rarity (<3%). Objective: To
      study the effectiveness in predicting the response and outcome with three
      prognostic scores in pediatric CML-chronic phase patients on front line Imatinib.
      Materials and Methods: We retrospectively analyzed the hospital records of newly
      diagnosed CML CP patients (aged <=18 years) from 2006 to 2010 for their risk
      score, cytogenetic response at 18 months and event free survival (EFS) at the end
      of 4 years. Events include loss of hematological response, loss of cytological
      response, progression to accelerated/blast phase (AP/BC). All received free
      Imatinib under Gleevac international patient assistance program. Results: Data of
      106 children was analyzed with median age of 13.5 (ranged 5-18 years) and male
      preponderance (M:F = 1.14:1). The distribution of children was 63%, 32% and 5% in
      Sokal low, intermediate and high risk respectively, 50%, 43% and 5% in
      Hasford/Euro low, intermediate and high risk respectively, 71% and 29% in EUTOS
      low and high risk respectively. The overall cumulative complete hematological
      response at the end of 3 month was 94%, and complete cytogenetic response at 12
      months was 75%. The CCyR at 18 month was seen in 90%,74% and 83% among Sokal low,
      intermediate and high risk groups respectively, 83%, 86% and 83% among
      Hasford/Euro low, intermediate and high risk groups respectively, 84% and 86%
      EUTOS low and high risk groups respectively. The EFS at the end of 48 months was
      seen in 87%,79% and 83% among Sokal low, intermediate and high risk groups
      respectively, 83%, 86% and 83% among Hasford/Euro low, intermediate and high risk
      groups respectively, 86% and 80% EUTOS low and high risk groups respectively.
      Conclusion: None of the scoring systems predicted the response and outcome
      effectively in children with CML CP on front line Imatinib.

PMID- 29200673
TI  - Sociodemographic Factors and Late-stage Diagnosis of Breast Cancer in India: A
      Hospital-based Study.
AB  - Context: Breast cancer (BC) is one of the major causes of cancer mortality in
      India. Late-stage diagnosis of BC is associated with poor survival.
      Identification of factors affecting late presentation of the disease could be an
      effective step to reduce BC mortality. Aims: To study the association of
      sociodemographic factors with BC stage at diagnosis. Settings and Design: The
      study is a retrospective analysis from the case records from a single
      institution. Subjects and Methods: Data for the year 2008 was collected from the
      hospital records. A total of 1210 cases were included for the analysis.
      Sociodemographic factors included were age, place of residence, religion, marital
      status, level of education, and occupation. Other study variables were family
      history, presence of comorbidity, and stage at diagnosis. Statistical Analysis:
      Association between sociodemographic factors by stage at diagnosis was tested
      using Chi-square statistics, with odds ratios (ORs) estimated through logistic
      regression modeling. Results: In the study cohort, 46% patients had reported at
      early stages and 54% at advanced stages. All factors were evaluated for being
      predictors of disease stage at presentation using univariate and multivariate
      logistic regression model. Women from urban background were less likely to
      present with advanced stage disease (OR = 0.64; 95% confidence interval [CI]:
      0.49-0.84) as compared to rural women. Similarly, illiterate women were also more
      likely to present with advanced-stage disease (OR = 1.55; 95% CI: 1.16-2.09).
      Conclusions: This data clearly indicate that the patients of rural background and
      of low education status are more likely than their respective counterparts to
      have an advanced stage of BC diagnosis. Our results may be considered the keys to
      determining how stage variation may be related to patients and community
      characteristics and where limited resources need to be invested to ensure early
      diagnosis of BC.

PMID- 29200675
TI  - Neurolymphomatosis: A Surreal Presentation of Lymphoma.
AB  - Background: Neurolymphomatosis is a neurologic complication poorly recognized by
      neurologists and oncologists and presents usually several months after successful
      treatment of systemic lymphoma. Other disorders that must be differentiated from
      these entities include peripheral-nerve or nerve root compression and
      paraneoplastic neuropathy. Aim: To describe the unusual occurrence of
      neurolymphomatosis in a patient of B-cell lymphoma. Method: Diagnosis was made by
      demonstration of enhancement of nerve roots on Magnetic Resonance Imaging of the
      brachial, lumbosacral plexus, peripheral nerves or by increased hyper-metabolic
      activity along the course of affected nerves on fluorodeoxyglucose positron
      emission tomography (FDG-PET). Results and Conclusion: MRI and PET-CT are imaging
      modalities of choice for evaluation of patients with lymphoma and suspected
      neural involvement. Treatment of neurolymphomatosis consists of focal
      radiotherapy and high-dose methotrexate therapy.

PMID- 29200676
TI  - Sociodemographic and Clinical Profile of Cervical Cancer Patients Visiting in a
      Tertiary Care Hospital in India.
AB  - Context: Cancer of the cervix is the most common genital tract malignancy in the
      female and is a major public health problem in the developing countries. Study of
      the sociodemographic and clinical profile of patients is the first step in
      planning control measures and treatment facilities. Aims: The aims of the study
      were to determine the sociodemographic and clinical profile of cervical cancer
      patients and study their association with other tumor-related factors. Settings
      and Design: This is a record-based retrospective study from a single institution.
      Subjects and Methods: The data on sociodemographic and clinical factors of 765
      cervical cancer patients visited and treated at tertiary care cancer hospital in
      Mumbai in 1 year period were analyzed. Statistical Analysis: Data were analyzed
      using descriptive statistics. Kruskal-Wallis and Chi-square test were used to
      assess relationship between variables. Results: The median age of the cohort was
      54 years and interquartile range was 16 years. Nearly 53.6% of patients were
      illiterate. About 88.10% of patient's had squamous cell carcinoma. Only 13% of
      cases had early stage disease and 77% of patient's had not taken any treatment
      before coming to the hospital. Of the total, about 26% patients also had
      concomitant comorbidities, of which hypertension was found to be the leading
      comorbid condition. Stage of disease was found to be significantly (P < 0.05)
      associated with age and educational status. Conclusion: This study highlights
      certain important baseline characteristics of cervical cancer patients. This
      basic information on profile of patients can help plan and optimum utilization of
      hospital services, especially in resource-poor countries like India.

PMID- 29200677
TI  - Evaluation of Intraoperative Cytological Smears for Diagnosis of Brain Tumors
      with Special Reference to Immunohistochemistry.
AB  - Context: Brain tumors are heterogeneous group of benign and malignant tumors of
      glial, meningeal, neuronal, embryonal, and lymphoid origin. Rapid intraoperative
      diagnosis of the nature of the tumor helps the surgeon to plan the extent of
      surgery and modify it accordingly. Aims: (1) To establish the validity and
      reliability of squash cytology in the intraoperative diagnosis of brain tumors.
      (2) To correlate with histopathological report and immunohistochemistry (IHC)
      profile. Settings and Design: Prospective, observational study. Subjects and
      Methods: prospective, observational study was conducted in the Department of
      Pathology in collaboration with the Department of Neurosurgery of a tertiary care
      hospital. One hundred and seven patients with symptomatic or radiologically
      detected brain tumors were included in the study. Intraoperative squash smears
      were stained with hematoxylin and eosin and rapid papanicolaou stain. Cytological
      diagnosis was recorded and communicated to the surgeon. Cytological findings were
      corroborated with histological findings subsequently. GFAP, Ki-67, and ER-PR IHC
      were used as additional markers. Statistical Analysis Used: Software used in
      statistical analysis of our study was MedCalc version 11.6 (Mariakerke, Belgium:
      MedCalc Software 2011). Results: A total of 107 cases were included in the study.
      Meningioma was the most common lesion. Overall sensitivity in our study to
      diagnose benign and malignant tumors was 94.7% and the specificity is 97.6% with
      positive and negative predictive value of 94.7% and 97.6%, respectively.
      Diagnostic accuracy was highest in pituitary adenoma. Conclusions: The
      combination of meticulous evaluation of clinical, radiological, and cytological
      findings helps in accurate and rapid diagnosis of brain tumors.

PMID- 29200678
TI  - Radiofrequency Ablation of Osteoid Osteoma in Common and Technically Challenging
      Locations in Pediatric Population.
AB  - Context: Percutaneous radiofrequency ablation (RFA) of osteoid osteoma has a high
      technical and clinical success rate. However, there is limited data on its use in
      the pediatric population, especially in technically challenging locations.
      Objective: The objective of this study was to assess the safety and efficacy of
      CT-guided percutaneous RFA of osteoid osteoma in pediatric population. Subjects
      and Methods: From June 2009 to May 2014, thirty patients with osteoid osteoma
      were treated with CT-guided RFA in common (25 cases) and technically challenging
      (five cases: four near articular surface and one in sacrum) locations. Therapy
      was performed under general anesthesia with a three-array expandable RF probe for
      6 min at 90 degrees C and power of 60-100 W. The patients were discharged next
      day under instruction. The treatment success was evaluated in terms of pain
      relief before and after (1 day, 1 month, and 6 months) treatment. Results:
      Technical success was achieved in all patients (100%). Primary clinical success
      was 96.66% (29 of total 30 patients) despite the pediatric population and
      atypical location. One patient had persistent pain after 1 month duration and
      were treated successfully with a second procedure (secondary success rate was
      100%). One patient had immediate complication of weakness of right hand and
      fingers extension. No delayed complications were observed. Conclusions: CT-guided
      RFA is relatively safe and highly effective for treatment of osteoid osteoma in
      pediatric population, even in technically difficult locations. Advance in
      Knowledge: Our study showed that if technical success is 100% and if strict
      desired temperature (90 degrees C) can be maintained for desired time (6 min)
      using controlled power (wattage) delivery (60-100 W), then high clinical success
      can be achieved even in pediatric population similar to adult population.

PMID- 29200679
TI  - Status of Serum and Salivary Ascorbic Acid in Oral Potentially Malignant
      Disorders and Oral Cancer.
AB  - Background and Aims: The aim of this study was to estimate the detoxification
      status of serum and saliva by assessing the serum and salivary Vitamin C in oral
      potentially malignant disorders and oral cancer. Subjects and Methods: A total of
      90 subjects, 30 subjects with oral potentially malignant disorders, 30 subjects
      with oral cancer, and 30 healthy subjects (controls) were included in the study.
      Serum and saliva were collected and levels of Vitamin C were assessed. Data
      obtained was analyzed using ANOVA test for the comparison between the groups.
      Post hoc Tukey's analysis was used for the comparison of the two study groups to
      the control group. Correlation between the groups was done using Pearson's
      correlation coefficient test. Results: The mean serum and salivary Vitamin C
      levels were decreased significantly in potentially malignant disorders and oral
      cancer when compared to healthy subjects. Conclusions: As significant reduction
      of Vitamin C is seen in saliva, it can be stated that saliva can be used as a
      reliable, noninvasive biomarker in diagnosis and management of potentially
      malignant disorders and oral cancer.

PMID- 29200680
TI  - Poor Risk Advanced Renal Cell Carcinoma: Outcomes from a Registry in a Tertiary
      Cancer Center.
AB  - Background: Poor-risk advanced Renal cell carcinoma (RCC) are an under-evaluated
      and difficult to treat subset of patients with poor prognosis. While Temsirolimus
      is the approved first line therapy for this category, Tyrosine kinase inhibitors
      (TKIs) are also commonly uses as initial treatment. We present an analysis of
      poor-risk advanced RCC treated in our institute. Materials and Methods: Patients
      diagnosed as poor-risk (as per Heng criteria) advanced RCC from June 2008 to
      December 2015 were analysed for baseline demographics, treatment received,
      toxicity (primarily Grade 3 and Grade 4), response rates (RR) and survival.
      Results: 60 patients (43 males, 17 females) with a median age of 53 years were
      included for final analysis. Median ECOG PS was 1, clear cell was the predominant
      histology (63.3%), and 46.7% of patients had greater than 2 sites of metastases.
      Sorafenib, Sunitinib, Temsirolimus and Pazopanib were used to treat 43.3%, 36.7%,
      8.3% and 6.7% of patients respectively, while 3 patients were offered upfront
      best supportive care. Common adverse events included skin rash (31.5%), HFS
      (Grade 2 and 3 - 30.8%), mucositis (26.3%), hypertension (24.5%), and
      dyslipidaemias (22.8%). 41 patients were available for response - overall
      response rate observed was 15%, while clinical benefit rate was 50%. Median
      progression free survival was 5.78 months (4.67-6.89) and median overall survival
      (OS) was 10.05 months (7.31-12.79). Conclusion: A majority of poor-risk
      metastatic RCC patients in our study were treated with TKIs and the survival
      outcomes appear to suggest that this strategy is a feasible alternative to
      Temsirolimus in the Indian setting.

PMID- 29200681
TI  - Clinicopathological Features and Treatment Outcomes in Ewing's Sarcoma Patients:
      A 10-year experience of Alexandria Clinical Oncology Department.
AB  - Background: Ewing's sarcoma (ES) is an aggressive tumor, which is usually
      associated with micrometastases in the circulation. Thus, systemic chemotherapy
      in addition to local control modality is essential to improve outcomes. The aim
      of this study was to evaluate clinicopathological features and treatment outcomes
      in patients with ES. Materials and Methods: Medical files of 74 patients with
      nonmetastatic ES treated at our centers between 2004 and 2014 were
      retrospectively evaluated. The clinicopathological parameters were extracted and
      statistically correlated with event-free survival (EFS) and overall survival
      (OS). Results: The median age of patients was 13 years. The median follow-up
      duration was 63.8 months. About two-thirds (58.1%) of patients were male. Pain
      (74.3%) was the most common presenting symptom. Extremities (48.6%) were the
      frequently affected sites. Thirty-two patients (43.2%) presented by tumors larger
      than 8 cm. All patients were treated with chemotherapy. Local therapies were
      surgery and/or radiotherapy. The 5-year EFS and OS were 44% and 57%,
      respectively. On multivariate analysis, EFS and OS were significantly associated
      with age, tumor site, and tumor size. Conclusions: Despite limited resources in a
      developing country, the survival rates of ES are comparable to that in developed
      countries, and prognostic factors are age, tumor site, and tumor size.

PMID- 29200682
TI  - Assessment of Angiogenesis in Children with Acute Lymphoblastic Leukemia Based on
      Serum Vascular Endothelial Growth Factor Assay.
AB  - Introduction: Vascular endothelial growth factor A (VEGFA) is a key proangiogenic
      cytokine. The role of angiogenesis in acute lymphoblastic leukemia (ALL) is still
      unclear. The purpose of the study was to assess angiogenesis in children with ALL
      based on serum VEGFA level determined at diagnosis and at remission with further
      participant subdivision into different risk groups. Materials and Methods: Forty
      children, aged 3-12 years (mean age: 8 years) with newly diagnosed ALL, were
      enrolled in the study. The control group (Group C) was twenty healthy children.
      According to the risk assessment, they were classified into a standard-risk
      group, an intermediate-risk group (IRG), or a high-risk group (HRG). Results: The
      median serum VEGFA levels at diagnosis were significantly higher in IRG and HRG
      as compared to Group C. The VEGFA levels at remission were significantly higher
      in all study groups, as compared to Group C. The differences in median values of
      serum VEGFA levels between the study groups both at diagnosis and at remission
      were not statistically significant. Conclusions: The angiogenesis in ALL seems to
      be intensified at diagnosis as a result of neoplasmatic bone marrow rebuilding
      and at remission as its intensive recovering.

PMID- 29200683
TI  - Physiogenomics in Etiopathogenesis of Cholangiocarcinoma.
AB  - Objective: Cholangiocarcinoma is a serious malignancy that is very common in the
      tropical countries. It is a kind of deadly primary hepatobiliary tumor. There is
      a wide spectrum of tumors with varying differentiation and malignancy grades.
      Although it has been known for a long time inmmedicine, there is no clear cut
      that this deadly cancer is genetic disorder or not. A systemic approach on the
      pathophysiology and genomics can provide useful information and help better
      understand the pathogenesis of cholangiocarcinoma. Methods: In this work, a
      standard bioinformatics physiological genomics analysis of cholangiocarcinoma was
      performed. Result: According to this work, there is no identified physiogenomics
      relationship for the cholangiocarcinoma. Conclusion: This might imply that the
      cholangiocarcinoma is directly due to environmental insult. It implies that there
      should be no specific gene that might contribute to the increased risk in the
      etiopathogenesis of cholangiocarcinoma.

PMID- 29200684
TI  - The Role of Mutation Testing in Patients with Chronic Myeloid Leukemia in Chronic
      Phase after Imatinib Failure and Their Outcomes after Treatment Modification:
      Single-institutional Experience Over 13 Years.
AB  - Introduction: BCR-ABL1 kinase domain mutations represent the most frequent
      mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy, being
      detected in 40%-50% of imatinib-resistant patients with chronic myeloid leukemia
      in chronic phase (CML-CP). Over 100 BCR-ABL1 single-point mutations have been
      reported in patients with imatinib-resistant CML. There were few studies reported
      from India on BCR-ABL kinase mutations in imatinib failure patients. We present
      our data on imatinib resistance mutation analysis (IRMA) and use of imatinib dose
      hike and 2nd-generation TKI at our institute. Materials and Methods: All patients
      with a diagnosis of CML in a university hospital from June 2003 to July 2016 and
      who were tested for IRMA in view of imatinib failure, those in CP, and age <18
      years were included in the study. Results: A total of 2110 cases of CML reviewed
      and 269 cases of CML with imatinib failure were analyzed. The male to female
      ratio was 1.7:1. The median age at presentation was 36 years (range: 18-66
      years). Among these, 26% were primary failures and 74% were secondary failures.
      The treatment was modified either as imatinib dose hike or nilotinib/dasatinib.
      Molecular response at 12 months was achieved in 25.7% in imatinib dose hike,
      46.6% in nilotinib, and 53.8% in dasatinib arms. The 4-year overall survival in
      mutation detected group was 37.5% and in nonmutated group was 87.7%. Conclusion:
      Imatinib-resistant mutations were more common in the cases with secondary failure
      though not statistically significant. T315I mutation was the common mutation
      found in the study. Imatinib dose hike to the failure cases resulted in optimal
      hematological response rates.

PMID- 29200685
TI  - A Study on Utilization and Evaluation of Antiemetics in Chemotherapy-induced
      Nausea and Vomiting.
AB  - Purpose: Chemotherapy-induced nausea and vomiting (CINV) are the major adverse
      effects of cancer chemotherapy. The objectives of this study are to evaluate the
      utilization of antiemetics in CINV and to assess the emetogenicity of
      chemotherapy and to investigate the incidence of acute and delayed CINV. Methods:
      A prospective observational study was carried out in patients undergoing
      chemotherapy. A suitable data collection form was designed to collect data
      regarding patient's demographics, cancer type, chemotherapy regimen, antiemetic
      prescribed, and incidence of CINV according to the standard methods utilizing
      morrow assessment of nausea and emesis form. Results: Among 200 patients enrolled
      in the study, with age range of 18-83 (52 +/- 11.65; mean +/- standard deviation)
      of both sexes (44% of male and 56% of female), 38.5% of patients received highly
      emetogenic chemotherapy and 46.5% received moderate emetogenic chemotherapy.
      Among the patients, 88% received 5HT3-RA in combination with corticosteroid (99%)
      and NK1-RA (40.5%). Despite the administration of antiemetic, the incidence of
      acute and delayed nausea after chemotherapy treatment was reported by 54% and
      15.5%, respectively. The comparable figures for acute and delayed vomiting were
      36.5% and 14.5%. Conclusion: The incidence of CINV among the patients was
      relatively high and it indicates that more attention is needed for the treatment
      of both acute and delayed CINV. It also gives an idea for implementation of more
      efficient antiemesis guideline in the clinical practice.

PMID- 29200686
TI  - An Investigation of Bayes Algorithm and Neural Networks for Identifying the
      Breast Cancer.
AB  - Context: Breast cancer is a biggest threat to women. X-ray mammography is the
      most effective method for early detection and screening of breast cancer. It is a
      tough challenge for the radiologist in reading mammography since it does not
      provide consistent result every time. Aim: To improve the primary sign of this
      disease, computer-aided diagnosis schemes have been developed. Using monitor,
      digital images of mammography are displayed and they can be lightened or darkened
      before they are printed on the film. Time factor is important to identify the
      abnormality in body such as breast cancer and lung cancer. Hence, to detect the
      tissues and treatment stages, image-processing techniques are improved in several
      medical areas. In this project, using low-level preprocessing techniques and
      image segmentation, the breast cancer detection is done. Methods: With the help
      of Bayes algorithm and neural networks (NNs), the type of the mammogram and
      stages is identified. For segmentation process, region-growing algorithm is used,
      which helps to find the affected portion, i.e., region of interest. Gray-level co
      occurrence matrix (GLCM) and texture feature are used for feature extraction.
      Results: Bayes algorithm is used for probability of identification, whereas NNs
      is used to reduce the probability level from 0-1000 to 0-1 in case of
      classification.

PMID- 29200687
TI  - Analytical Study on the Efficacy of Neoadjuvant Chemotherapy Using a Combination
      of Methotrexate, Bleomycin, and Cisplatin in the Management of Advanced Squamous
      Cell Carcinoma of the Buccal Mucosa.
AB  - Context: Cancers of the buccal mucosa (CaBM) predominate in India with late-
      stage diagnosis and poor survival, necessitating optimal management. Aim: Our
      study aimed at testing the efficacy of combination neoadjuvant chemotherapy
      (NACT) using cisplatin (CIS), bleomycin (BL) and methotrexate (MTX) for reducing
      tumour volume prior to surgery. Methodology: Patients with advanced CaBM (stage
      III, IV, n = 100) were administered 6 rounds of NACT with CIS, BL and MTX.
      Responses, toxicity and 6-month follow-up was monitored statistically to
      determine persistence of response. Results: A significant number of patients
      showed objective response as either complete or partial tumour regression with
      subjective response as reduced trismus, pain, salivation and foul odour.
      Moreover, there was mild associated toxicity and tumour regression continued in
      most patients even after 6-month follow-up. Conclusion: Our study indicates that
      NACT with CIS, BL and MTX offers a good therapeutic alternative in terms of
      significant objective and subjective responses, low toxicity, affordable costs
      and persistent responses.

PMID- 29200688
TI  - Round Cell Tumors: Classification and Immunohistochemistry.
AB  - Round cell tumors as the name suggest are comprised round cells with increased
      nuclear-cytoplasmic ratio. This group of tumor includes entities such as
      peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non
      Hodgkin's lymphoma, neuroblastoma, hepatoblastoma, Wilms' tumor, and desmoplastic
      small round cell tumor. These round cells tumors are characterized by typical
      histological pattern, immunohistochemical, and electron microscopic features that
      can help in differential diagnosis. The present article describes the
      classification and explains the histopathology and immunohistochemistry of some
      important round cell tumors.

PMID- 29200689
TI  - Acute Lymphoblastic Leukemia as Secondary Malignancy in a Case of Ewing's Sarcoma
      on Treatment.
AB  - The survival of Ewing's sarcoma (ES) has improved due to advances in both local
      and systemic therapy. This has given rise to an increased detection of second
      malignant neoplasms which can be in the form of solid tumors and hematological
      malignancies. The most common hematological malignancies are acute myeloid
      leukemia/myelodysplastic syndrome. Acute lymphoblastic leukemia (ALL) is
      relatively uncommon in occurrence in this setting. Furthermore, the average
      refractory period for hematological malignancies varies from 3 to 5 years. We
      report a case of a young female who developed ALL while on adjuvant therapy for
      ES.

PMID- 29200690
TI  - Unusual Presentation of Metanephric Stromal Tumor in a Neonate.
AB  - Metanephric stromal tumor (MST) of kidney is an under-reported benign stromal
      specific renal neoplasm with good prognosis. This tumor is to be differentiated
      from congenital mesoblastic nephroma and clear-cell sarcoma of the kidney. In
      this case report, we describe the imaging, gross, and microscopic features of MST
      with ischemic left kidney in a 1-month-old child and discuss treatment with
      relevant literature.

PMID- 29200691
TI  - A Case Report of Newly Diagnosed Epithelial Ovarian Carcinoma Presenting with
      Spontaneous Tumor Lysis Syndrome and Its Successful Management with Rasburicase.
AB  - Tumor Lysis Syndrome (TLS) commonly occurs in hematological malignancies, but it
      is very rare in patients with a solid tumor. In cases of solid tumors, TLS
      usually occurs spontaneously or after the initiation of anticancer therapy, and
      it has a high mortality rate. This syndrome consists of a constellation of
      laboratory findings such as hyperuricemia, hyperkalemia, hyperphosphatemia, and
      hypocalcemia known as laboratory TLS. When clinical complications such as
      seizures, acute renal failure, and cardiac dysrhythmias occur in patients with
      laboratory TLS, the syndrome is called clinical TLS. The present case report is
      sixth in the series and probably the first case report of spontaneous TLS in a
      newly diagnosed patient of epithelial ovarian cancer and also shows the
      effectiveness of single dose (1.5 mg) of rasburicase along with adequate
      hydration to rapidly reverse TLS and also timely initiation of definitive
      treatment. The patient was then able to complete successfully the planned
      neoadjuvant chemotherapy and surgery without any long-term sequela.

PMID- 29200692
TI  - A Novel Presentation of Cutaneous Angiosarcoma: A Case Report and Review.
AB  - We report a case of a 70-year-old male, with slowly widening induration,
      ulceration, and oozing for 3 months on the scalp and face. The diagnosis of
      aggressive cutaneous angiosarcoma was made on histopathology and immunochemistry
      from the biopsy material from the involved area of the skin.

PMID- 29200693
TI  - Pilomatrix Carcinoma Masquerading as Breast Carcinoma.
AB  - Pilomatrix carcinoma is an exceedingly rare skin adnexal neoplasm derived from
      piliferous follicles, usually occurring in the head and neck region. Localization
      of this tumor in the breast is a rarity. We now report an unusual case of a 49
      year-old female who presented with a palpable mass in the left breast for 2
      years. Mammogram revealed a large, lobulated opacity with calcification, and
      positron emission tomography-computed tomography showed a metabolically active
      soft tissue mass measuring 15 cm involving all the quadrants of the left breast.
      Subsequently, the patient underwent radical mastectomy, and histopathologic
      diagnosis of pilomatrix carcinoma of the breast was offered. Pilomatrix
      carcinoma, although exceedingly rare, can have an intramammary location and can
      be misdiagnosed as breast carcinoma on limited material. A high index of
      suspicion is required to arrive at an accurate diagnosis so as to obviate
      neoadjuvant chemotherapy.

PMID- 29200694
TI  - Pancreatitis in Acute Promyelocytic Leukemia: Drug-induced or Differentiation
      Syndrome?
AB  - Acute promyelocytic leukemia (APL) constitutes about 15% of all acute myeloid
      leukemia patients and can now be treated even without any chemotherapy, with all
      trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Acute pancreatitis (AP) is
      a rare adverse event in APL, which is primarily reported to be secondary to
      hypertriglyceridemia. Here, we have reported AP developed in a patient of APL,
      during induction with ATRA and ATO, but it was not associated with
      hypertriglyceridemia. Rather, it was associated with respiratory distress and
      weight gain, coincidental leukocytosis, bilateral pleural effusion, and edematous
      pancreatitis without any necrosis. Hence, AP in this case is diagnosed to be a
      manifestation of differentiation syndrome, and it responded to steroid.

PMID- 29200695
TI  - Metaplastic Carcinoma of Breast and Neurofibromatosis 1: A Rare Association.
AB  - Neurofibromatosis 1 (NF1) patients are generally at higher risk of developing
      common malignant tumors such as brain and soft tissue tumors. These patients are
      5-fold increased the risk of developing breast cancer by the age of 50 years
      after that the risk remains the same. The most common reported cancer is
      infiltrating duct carcinoma. We report a case of 61-year-old female with NF1
      presented with pain and breast lump for the past 2 months. On mammography, a
      retroareolar solid cystic lesion measuring 32 mm * 30 mm * 30 mm was noted which
      was definitive for malignancy. Right-modified radical mastectomy with axillary
      lymph node dissection was done which revealed a neoplasm composed of glandular
      and squamous components. Immunohistochemically, these cells were triple negative
      for estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2-neu and expressed markers of basal cell differentiation. The final
      pathological staging was T2N0M0. This is the fourth case report in the English
      literature with such association. In this case report, we discussed the
      importance of breast cancer screening in such patients along with a review of the
      literature.

PMID- 29200696
TI  - Human Leukocyte Antigen-B27: The Genetic Predisposition Leading to Reactive
      Arthritis during Induction Phase Chemotherapy for Acute Myeloid Leukemia.
AB  - We report a case of reactive arthritis (ReA) during induction phase chemotherapy
      of a 15-year-old male patient with acute myeloid leukemia (AML) M4 with inv(16),
      most probably due to a genetic predisposition of being human leukocyte antigen
      b27 (HLA-B27) positive. The episode of ReA recurred during consolidation therapy;
      however, the patient was asymptomatic after the completion of treatment. The link
      between HLA-B27 and a large family of inflammatory rheumatic diseases is a well
      established fact, but interestingly, there is also a molecular link between HLA
      B27 and hematological malignancies. This case brings to our notice, the common
      immunological, molecular, and microbiological link between AML, HLA-B27, and ReA.
      It also emphasizes the fact that clinicians should have a high index of suspicion
      of HLA-B27 positivity, if a case of AML develops arthritis during chemotherapy,
      since early introduction of immunosuppressive medications for arthritis may
      reduce morbidity and prevent delay in the administration of further chemotherapy
      cycles.

PMID- 29200697
TI  - Uncommon Adverse Effects of Commonly Used Chemotherapeutic Agents in Medical
      Oncology Practice: A Series of Two Cases of Hand-Foot Syndrome.
AB  - Chemotherapy has an increasing potential for cure and palliation of most forms of
      cancer in different stages. However, its use is associated with a multitude of
      side effects some very common and few very rare. We present two patients of
      metastatic nonsmall lung cancer who had severe forms of hand-foot syndrome with
      two different classes of antineoplastic drugs and have to discontinue
      chemotherapy.

PMID- 29200698
TI  - Extrarenal Extracranial Rhabdoid Tumor of the Pelvis in a Young Adult-management
      of a Challenging Case.
AB  - Rhabdoid tumor commonly occurs in the kidney and has an aggressive clinical
      course with high mortality. Central nervous system is the most common extrarenal
      site. Extrarenal extracranial rhabdoid tumor (EERT) is rare. EERT usually
      presents in childhood, and presentation in adulthood is extremely rare. This
      tumor is often difficult to diagnose, and there is no established standard of
      care due to the paucity of cases. We herein report a case of extrarenal rhabdoid
      tumor of the pelvis in a young adult and discuss the presentation and possible
      treatment options of this rare tumor.

PMID- 29200699
TI  - Metastatic Epithelioid Malignant Peripheral Nerve Sheath Tumor in a Known Case of
      Neurofibromatosis-1, Cytomorphological Appearance, and Critical Analysis of
      Immunohistochemistry.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors
      commonly arising from nerve roots in the extremities with a predilection in
      neurofibromatosis (NF) patients. MPNSTs are known to behave aggressively, with
      worse prognosis in nonresectable cases, and a 5-year survival of about 52% and
      15% in resectable and unresectable cases, respectively. Although cytological
      diagnosis in a known case of NF-1 is possible, however, in the absence of any
      associated syndrome in a sporadic case, it is very challenging to accurately
      diagnose this tumor. Till date, to the best of our knowledge, only three cases of
      epithelioid MPNST correctly diagnosed on cytological examination have been
      described. We are presenting another case of epithelioid MPNST in a 40-year-old
      patient with stigmata of NF-1 since childhood, diagnosed on fine-needle
      aspiration cytology from the left flank mass with subsequent histopathology from
      left inguinal lymph node metastasis.

PMID- 29200700
TI  - Extrapulmonary Tuberculosis of Lymph Node Coexist with Diffuse Large B-cell
      Lymphoma: A Case Report.
AB  - Extrapulmonary tuberculosis (TB) coexistent with lymphomas in the same organ are
      rare. Here, we report a case of a 14-year-old male patient who had cauliflower
      like ulcerated mass over cervical lymphadenopathy. He was diagnosed
      extrapulmonary TB. Unresponsiveness of anti tubercular treatment (anti
      tubercular) treatment after 6 months, he was diagnosed as diffuse large B-cell
      lymphoma.

PMID- 29200701
TI  - A Rare Extramedullary and Extralymphoid Presentation of Mixed Phenotypic Blastic
      Hematolymphoid Neoplasm: A Study of Two Cases.
AB  - Mixed phenotype acute leukemia (MPAL) is a rare hematolymphoid neoplasm,
      representing only 3%-5% of acute leukemia. Although MPAL has been sufficiently
      described in the literature, its extramedullary presentation as a solitary lesion
      without leukemic (bone marrow [BM]) involvement is rarely described. We are
      presenting two cases of mixed phenotypic blastic hematolymphoid neoplasms without
      leukemic involvement at disease presentation in 8-year-old female and 21-year-old
      male patients. Both the cases had extralymphatic bone involvement in the form of
      solitary bone lesion. Initially, there was no leukemic involvement in both the
      cases, but the second case progressed to acute leukemia during the course of the
      disease. On immunophenotypic evaluation, both the cases revealed blasts showing
      unequivocal evidence of myeloid and B-lymphoid lineage commitment. These cases
      were difficult to categorize either into MPAL as the BM was not involved or into
      lymphoblastic lymphoma due to coexpression of myeloid differentiation. Therefore,
      we chose to classify them as a bi/mixed phenotypic blastic hematolymphoid
      neoplasm. Detailed immunophenotypic analysis either by immunohistochemistry or
      flow cytometric immunophenotyping is important for the diagnosis of such cases as
      they have a poor prognosis.

PMID- 29200702
TI  - Affordable and Safe Health Care for All Children: Lessons Learned from the Use of
      Peg-asparaginase in a Developing Country.
AB  - Peg-asparaginase has widely replaced the use of conventional asparaginase in
      treatment of children with acute lymphoblastic leukaemia in developed countries.
      In developing countries like India, with financial constraints being a part of
      clinical challenge to the treatment of cancers, uniform use of Peg-asparaginase
      in all children is not practically possible. However, we found by a retrospective
      analysis of 211 children treated for acute lymphoblastic leukaemia, uniform use
      of this drug was feasible with indigenous techniques like storing the drug with
      strict cold chain maintenance and sharing the drug amongst 2 or 3 patients to
      reduce the burden on each family. We have not found increased rates of infection
      or any loss of efficacy of the drug due to prolonged storage.

PMID- 29200703
TI  - Rhabdomyosarcoma of the Iliopsoas: A Retroperitoneal Misdiagnosis.
AB  - Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma. The already documented data
      regarding RMS state that it is more prevalent in males than females and also that
      its occurrence is more in Caucasians than Asians. The current incidence of RMS is
      4.5 cases/million, and thus, it is a very rare cancer. The undifferentiated type
      is the most aggressive one with a rare presentation in the retroperitoneum.
      Overall, this case emphasizes that consideration should be given to wide range of
      diagnosis and that frozen section is the gold standard for a confirmatory
      diagnosis, as the first biopsy showed benign cells within the tumor. The emphasis
      on the interventions related to imaging to prevent the chance of aggravated
      presentation in the terminal stage of somatic comorbidities like loss of power.
      Radical excision of the mass along with normal iliopsoas tendon was done and
      referred to a cancer specialty center for further chemotherapy. To the best of my
      knowledge, this is the only case of RMS of the iliopsoas.

PMID- 29200704
TI  - Fibroepithelial Polyp with Sebaceous Hyperplasia: A Case Report.
AB  - Fibro epithelial Polyp (FEP) is a polypoid outgrowth of epidermis and dermal
      fibro vascular tissue. This polyp is most commonly found in oral cavity, neck and
      axilla, though any skin fold may be affected like groin area. We describe a case
      of a 25-year-old male patient with a growth over the anterior rugae region of
      hard palate since 3 years. Based on histological appearance, diagnosis of
      sebaceous gland hyperplasia in fibroepithelial polyp was given which itself is a
      rare entity, and in our case, it was encountered at the rarest of sites.

PMID- 29200705
TI  - A Novel Translocation: t(2;14)(p12;q32) in a Case of Precursor B-acute
      Lymphoblastic Leukemia.

PMID- 29200706
TI  - Estimation of Cancer Risk Due to Exposure to Airborne Particle Emission of a
      Commercial Three-dimensional Printer.

PMID- 29200707
TI  - WWOX rs11644322 Polymorphism, Gemcitabine, and Pancreatic Cancer.

PMID- 29200708
TI  - Biomechanics of ACL.

PMID- 29200709
TI  - Total knee arthroplasty in young patients: Factors predictive of aseptic failure
      in the 2nd-4th decade.
AB  - Objective: In a recently published article we reviewed our long term outcomes of
      TKA in young patients (<55) with end stage OA. The purpose of this study was to
      identify what additional factors may predict aseptic failure in these young
      patients. Methods: A retrospective review of all patients in our young TKA
      database was performed, and included failure only for mechanical wear and
      loosening. Results: The IB-II prosthesis, a thin polyethylene (<9 mm), and higher
      Knee Society functional class at midterm follow-up was associated with higher
      failure rate. Conclusion: This study helps better identify the etiology of failed
      young patient TKA.

PMID- 29200710
TI  - Identification of Hepatoprotective Constituents in Limonium tetragonum and
      Development of Simultaneous Analysis Method using High-performance Liquid
      Chromatography.
AB  - Background: Limonium tetragonum, a naturally salt-tolerant halophyte, has been
      studied recently and is of much interest to researchers due to its potent
      antioxidant and hepatoprotective activities. Objective: In the present study, we
      attempted to elucidate bioactive compounds from ethyl acetate (EtOAc) soluble
      fraction of L. tetragonum extract. Furthermore, the simultaneous analysis method
      of bioactive EtOAc fraction of L. tetragonum has been developed using high
      performance liquid chromatography (HPLC). Materials and Methods: Thirteen
      compounds have been successfully isolated from EtOAc fraction of L. tetragonum,
      and the structures of 1-13 were elucidated by extensive one-dimensional and two
      dimensional spectroscopic methods including 1H-NMR, 13C-NMR, 1H-1H COSY,
      heteronuclear single quantum coherence, heteronuclear multiple bond correlation,
      and nuclear Overhauser effect spectroscopy. Hepatoprotection of the isolated
      compounds against liver fibrosis was evaluated by measuring inhibition on hepatic
      stellate cells (HSCs) undergoing proliferation. Results: Compounds 1-13 were
      identified as gallincin (1), apigenin-3-O-beta-D-galactopyranoside (2), quercetin
      (3), quercetin-3-O-beta-D-galactopyranoside (4), (-)-epigallocatechin (5), (-)
      epigallocatechin-3-gallate (6), (-)-epigallocatechin-3-(3"-O-methyl) gallate (7),
      myricetin-3-O-beta-D-galactopyranoside (8), myricetin-3-O-(6"-O-galloyl)-beta-D
      galactopyranoside (9), myricetin-3-O-alpha-L-rhamnopyranoside (10), myricetin-3-O
      (2"-O-galloyl)-alpha-L-rhamnopyranoside (11), myricetin-3-O-(3"-O-galloyl)-alpha
      L-rhamnopyranoside (12), and myricetin-3-O-alpha-L-arabinopyranoside (13),
      respectively. All compounds except for 4, 8, and 10 are reported for the first
      time from this plant. Conclusion: Myricetin glycosides which possess galloyl
      substituent (9, 11, and 12) showed most potent inhibitory effects on the
      proliferation of HSCs. SUMMARY: In the present study, we have successfully
      isolated 13 compounds from bioactive fraction of Limonium tetragonum. The
      structures of compounds isolated have been fully elucidated, and hepatoprotective
      activities of compounds against liver fibrosis were evaluated by measuring
      inhibition on hepatic stellate cells undergoing proliferation. Furthermore, the
      simultaneous analysis method of bioactive ethyl acetate fraction of L. tetragonum
      has been developed using HPLC. Ten compounds identified herein are reported for
      the first time from this plant.Abbreviations used: HSQC: Heteronuclear single
      quantum coherence; HMBC: Heteronuclear multiple bond correlation; NOESY: Nuclear
      Overhauser effect spectroscopy; EGCG: Epigallocatechin-3-gallate; EGC:
      Epigallocatechin; HSC: Hepatic stellate cell; MTT: 3-(4,5-dimethylthiazol-2-yl)
      2.5-diphenyltetrazolium bromide.

PMID- 29200711
TI  - Biological Activities and Cytotoxicity of Eperua oleifera Ducke Oil-resin.
AB  - Background: The oil-resin of Eperua oleifera Ducke has been used in popular
      medicine similarly to the copaiba oil (Copaifera spp.). Objective: This study
      aimed to investigate the effects of the acid fraction of E. oleifera oil-resin
      (AFEOR) on cell proliferation, collagen production in human fibroblasts,
      inhibition of metalloproteinases, and cytotoxicity against tumor cell lines.
      Materials and Methods: Acid fraction of E. oleifera was fractionated in the ion
      exchange column chromatography. Cytotoxicity and genotoxicity were evaluated by
      Alamar Blue(r) and Cometa assay. The inhibition of metalloproteinases was
      performed by zymography and Western blotting. Results: The predominant acidic
      diterpenes in the AFEOR were copalic and hardwickiic acids. AFEOR caused
      morphology alteration and decrease of proliferation at concentrations higher than
      5 MUg/mL. It also caused significant collagen proliferation in fibroblasts. It
      showed cytotoxicity against tumoral and nontumoral cell lines, with IC50 values
      ranging from 13 to 50 MUg/mL, and a hemolytic activity with an IC50 value of
      38.29 MUg/mL. AFEOR inhibited collagenase activity, with an IC50 value of 46.64
      MUg/mL, and matrix metalloproteinase-2 (MMP)-2 and MMP-9 in HaCaT cells or MMP-1
      expression in MRC-5 cells. AFEOR induced genotoxicity in MRC-5 cells with a DNA
      damage index between 40% and 60% when compared to the negative controls (0%-20%).
      Conclusion: For the first time, biological activities from oil-resin E. oleifera
      demonstrated ratifying somehow its popular use. SUMMARY: Analysis of crude oil
      resin and fractionation of diterpenic fraction was performance using selective
      ion-exchange column chromatographyCytotoxicity analysis and morphology were
      performed with different cell linesCollagen production in human fibroblasts,
      inhibition of metalloproteinases were demonstrated by zymography and Western
      blotting. Abbreviations used: AFEOR: Eperua oleifera oil-resin.

PMID- 29200712
TI  - Evaluating the Feasibility of Five Candidate DNA Barcoding Loci for Philippine
      Lasianthus Jack (Lasiantheae: Rubiaceae).
AB  - Introduction: The pantropical genus Lasianthus Jack is identified for high
      phenotypic plasticity making traditional taxonomic identification difficult.
      Having some members with important medicinal properties, a precise complimentary
      identification through DNA barcoding is needed for species delineation. Materials
      and Methods: In this study, 12 samples representing six Philippine Lasianthus
      species were used to determine the most efficient barcoding loci among the cpDNA
      markers (matK, rbcL, rps16, and trnT-F) and nrDNA (ITS) based on the criteria of
      universality, discriminatory power, and resolution of species. Results: The
      results revealed that ITS has the recommended primer universality, greatest
      interspecific divergences, and average resolution of species. Among the cpDNA
      markers, matK and rbcL are recommended but with minimal resolution of species.
      While trnT-F showed moderate interspecific variations and resolution of
      Lasianthus species, rps16 has the lowest interspecific divergence and resolution
      of species. Conclusion: Consequently, ITS is the potential ideal DNA barcode for
      Lasianthus species. SUMMARY: ITS, matK, and rps16 markers have the excellent
      amplification and sequence qualityITS marker has the highest interspecific
      divergence with the maximum values, followed by matK, rbcL, trnT-F, and rps16,
      respectivelyAll markers except rps16 yielded average resolution to Lasianthus
      speciesITS marker is the most ideal locus in terms of excellent universality,
      high interspecific discriminatory ability, and average species resolution.
      Abbreviations used: ITS: Internal Transcribe Spacer, matK: maturase K, rbcL:
      ribulose-1,5-biphospahte-carboxylase, rps16: ribosomal protein 16 small subunit
      gene.

PMID- 29200713
TI  - Gastroprotective and Ulcer Healing Effects of Camel Milk and Urine in HCl/EtOH,
      Non-steroidal Anti-inflammatory Drugs (Indomethacin), and Water-Restraint Stress
      induced Ulcer in Rats.
AB  - Background: Camel milk has been reportedly used to treat dropsy, jaundice,
      tuberculosis, and diabetes while camel urine is used to treat diarrhea and
      cancer. However, there is no scientific evidence on the antiulcer activity of
      camel milk and urine. Thus, the present is designed to investigate the
      gastroprotective and ulcer healing effect of camel milk and urine on
      experimentally induced gastric ulcer models in rats. Materials and Methods: The
      gastroprotective effect was investigated in HCl/EtOH, water-restraint stress
      (WRS) and non-steroidal anti-inflammatory drugs (indomethacin)-induced ulcer
      models while ulcer healing activity was investigated in indomethacin-induced
      ulcer model. Cimetidine (100 mg/kg) was used as a standard antiulcer drug.
      Results: Acute toxicity study done up to a dosage of 10 ml/kg of camel milk and
      urine showed no signs of toxicity and mortality among the rats, indicating the
      present dosage of 5 ml/kg is safe to be administered to the rats. In the HCl/EtOH
      model, oral administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and
      camel milk (5 ml/kg) significantly (P < 0.05) inhibited gastric lesions by 83.7,
      60.5 and 100%, respectively. In the WRS-induced model, cimetidine, and camel
      urine showed an ulcer inhibition of 100% while camel milk showed an inhibition of
      50%. Similarly, in the indomethacin-induced ulcer model, cimetidine, camel milk,
      and urine showed an ulcer inhibition of 100, 33.3, and 66.7%, respectively. In
      addition, camel milk and urine also showed a significant (P < 0.05) ulcer healing
      effect of 100% in indomethacin-induced ulcer model, with no ulcers observed as
      compared to that of cimetidine, which offers a healing effect of 60.5%.
      Conclusion: The antiulcer activity of camel milk and urine may be attributed to
      its cytoprotective mechanism and antioxidant properties. SUMMARY: Acute toxicity
      findings revealed the dosage of 10 ml/kg of camel milk and urine seems no toxic
      and indicating the dosage of 5 ml/kg is safe to be administered to the ratsOral
      administration of cimetidine (100 mg/kg), camel urine (5 ml/kg), and camel milk
      (5 ml/kg) significantly inhibited gastric lesions by 83.7, 60.5 and 100% in the
      HCl/EtOH experimental modelThe results of this investigation have proven that
      camel milk and urine showed strong ulcer healing effect in indomethacin-induced
      gastric damage. Abbreviations used: NSAIDs: Non-steroidal anti-inflammatory
      drugs, UI: Ulcer index, ANOVA: One-way analysis of variance, WRS: Water-restraint
      stress, ROS: Reactive oxygen species.

PMID- 29200714
TI  - Simultaneous Determination of Ten Constituents in Chaiqin Qingning Capsule by
      High-performance Liquid Chromatography Coupled with Triple-quadrupole Mass
      Spectrometry.
AB  - Background: Chaiqin Qingning Capsule (CQQNC) was a prescription of Traditional
      Chinese Medicine with the effects of clearing away heat and removing toxin,
      harmonizing the exterior and interior, it was widely used in Asian, for example,
      China and Japan, different batches of the raws materials and different processing
      time may be the vital factor which raised a challenge to control the quality of
      the CQQNC. Experimental Methods: In this experiment, a high-performance liquid
      chromatography-mass spectrometry/MS (HPLC-MS/MS) method was developed to
      simultaneously determine ten bioactive components for the quality control of
      CQQNC. Chromatographic separation was achieved using an XBridge BEH C18 column
      (150 mm * 4.6 mm, 2.5 MUm) with a mobile phase composed of 10 mm aqueous ammonium
      acetate and acetonitrile using a gradient elution in 20 min. This study was
      conducted by multiple reaction monitoring mode through electrospray ionization
      resource with a negative ionization mode. Results: The established method was
      validated with good performance of precision, accuracy, stability, and
      reproducibility and was utilized to simultaneously quantify ten constituents of
      CQQNC obtained from seven different batches. Conclusion: It is the first time to
      report the rapid and simultaneous analysis of the ten compounds in CQQNC by HPLC
      MS/MS and apply to determine 10 constituents in 7 batches of CQQNC bought from
      drug store in china. This method could be considered as good quality criteria to
      control the quality of CQQNC. SUMMARY: In this paper, a simple, specific, and
      rapid high-performance liquid chromatogram coupled with triple-quadrupole mass
      spectrometry method for simultaneous quantification of ten constituents in
      Chaiqin Qingning Capsule has been developed for the first time. This method could
      be considered as good quality criteria to control the quality of CQQNC.
      Abbreviations used: CHM: Chinese herbal medicine; TCM: Traditional Chinese
      Medicine; CQQNC: Triple-quadrupole mass spectrometry Chaiqin Qingning Capsules;
      HPLC-MS/MS: High liquid chromatography equipped with tandem mass spectrometry;
      ESI: Electrospray ionization; DP: Declustering potential; CE: Collision energy;
      RSD: Relative standard deviation; LOD: Limit of detection; LOQ: Limit of
      quantity.

PMID- 29200715
TI  - Antitumor Effects of Ethanol Extracts from Hyptis Rhomboidea in H22 Tumor-bearing
      Mice.
AB  - Background: Research the antitumor effects of ethanol extracts from Hyptis
      rhomboidea in H22 tumor-bearing mice. At the fist-stage of the experiments, the
      research team took MTT method to measure the antitumor activity in vitro, then
      selected the most inhibitory tumor cell strain as the test object of antitumor
      activity in vivo, established three models of a solid tumor H22 liver cancer,
      ascites tumor, and immunodeficiency in male mice. From inflammatory factor, liver
      toxicity, in vivo antioxidant index to observe antitumor activity of ethanol
      extracts from H. rhomboidea. Materials and Methods: Hundred and twenty ICR male
      mice were used to establish three models of a solid tumor H22 liver cancer,
      ascites tumor, and immunodeficiency in male mice and models group of a solid
      tumor H22 liver cancer randomly divided into six groupshe normal control group,
      the model control group, the positive group (cyclophosphamide), the sample
      treated group (high - 1.300 g/kg, medium - 0.750 g/kg, low - 0.373 g/kg). The
      animals were sacrificed 15d after oral administration and tumors were taken out
      for the tumor weights and antitumor rates. Blood in eyeball was collected for the
      determination of aspartate transaminase, alanine transaminase, malondialdehyde
      (MDA), superoxide dismutase (SOD), interleukin (IL)-2, and tumor necrosis factor
      (TNF)-alpha in serum. Sections of tumor issue were prepared, and morphological
      changes in tumor tissue cells were observed using hematoxylin and eosin staining
      technique. Results: The results showed that ethanol extracts from H. rhomboidea
      have a certain inhibitory effect on the digestive tumor cells. In solid tumor
      model, the inhibitory rate is up to 68.84% of the high dose of treated group from
      H. rhomboidea, and H. rhomboidea could improve the immune organ index, decrease
      the concentration of TNF-alpha and IL-2 in serum. In ascites tumor model, H.
      rhomboidea could slow down weight gain in mice and prolong the survival time; in
      immunodeficiency model, H. rhomboidea could improve the serum TNF-alpha and, IL-2
      levels, increase SOD activity, and reduce MDA content, so as to achieve antitumor
      effect. Conclusions: Ethanol extracts from H. rhomboidea have obvious antitumor
      activity in vivo and can improve a tumor-burdened mice inflammation factors,
      improve the survival quality of H22 tumor mice, and enhance immunity and
      antitumor activity. SUMMARY: Ethanol extracts from Hyptis rhomboidea have obvious
      antitumor activity without obviously liver damageThe experiment results prompt
      that the antitumor activity probably caused by decreasing the inflammatory
      factors, improve the survival quality, enhance the abnormal cytokines and
      scavenging free radicals, and raising autoimmune function in H22 tumor bearing
      mice. Abbreviations used: H. rhomboidea: Hyptis rhomboidea; AST: Aspartate
      transaminase; ALT: Alanine transaminase; MDA: Malondialdehyde; SOD: Superoxide
      dismutase; IL-2: Interleukin 2; TNF-alpha: Tumor Necrosis Factor-alpha; CTX:
      Cyclophosphamide.

PMID- 29200716
TI  - Antioxidant and Inhibitory Effects of Saponin Extracts from Dianthus basuticus
      Burtt Davy on Key Enzymes Implicated in Type 2 Diabetes In vitro.
AB  - Context: Dianthus basuticus is a plant of South African origin with various
      acclaimed pharmaceutical potentials. Aims: This study explored the antioxidant
      and antidiabetic activities of saponin extract from D. basuticus in vitro.
      Materials and Methods: Antioxidant activity of saponin was evaluated by 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (*NO)-free radical scavenging
      activity while antidiabetic potentials were measured by the alpha-amylase and
      alpha-glucosidase inhibitory activities of the saponin extract. Results: The
      results showed that the saponin extract, compared with quercetin, displayed
      better DPPH (IC50 = 6.95 mg/ml) and NO (IC50 = 3.31 mg/ml) radical scavenging
      capabilities. Similarly, the saponin extracts elicited stronger alpha-glucosidase
      (IC50 = 3.80 mg/ml) and moderate alpha-amylase (IC50 = 4.18 mg/ml) inhibitory
      activities as compared to acarbose. Saponin exhibited a competitive mode of
      inhibition on alpha-amylase with same maximum velocity (Vmax) of 0.0093 mM/min
      for saponin compared with control 0.0095 mM/min and different the Michaelis
      constant (Km) values of 2.6 * 10-6 mM and 2.1 * 10-5 mM, respectively, while for
      alpha-glucosidase, the inhibition was uncompetitive, Vmax of 0.027 mM/min
      compared with control 0.039 mM/min and Km values of 1.02 * 10-6 mM and 1.38 * 10
      6 mM, respectively. The gas chromatography-mass spectrometric analysis revealed
      the presence of bioactive like beta- and alpha-amyrin, 3-O-methyl-D-glucose,
      methyl commate, and olean-12-en-3-beta-ol. Conclusion: Overall, the data
      suggested that the saponin extract from D. basuticus has potentials as natural
      antioxidants and antidiabetics. SUMMARY: Saponin extract from Dianthus basuticus
      displayed promising antidiabetic and antioxidant activitySaponin competitively
      and uncompetitively inhibited a-amylase and a-glucosidase, respectivelyThe
      stronger inhibition of alpha-glucosidase and moderate inhibition of alpha-amylase
      by saponin extract from D. basuticus is promising good antidiabetes compared with
      existing drugs with associated side effects. Abbreviations used: DPPH: 2,2
      diphenyl-1-picrylhydrazyl, Km: The Michaelis constant, Vmax: Maximum velocity,
      ROS: Reactive oxygen species, NIDDM: Non-insulin-dependent diabetes mellitus,
      UFS: University of the Free State, GC-MS: Gas chromatography-mass spectrometric,
      MS: Mass spectrometry, NIST: National Institute of Standards and Technology, DNS:
      3,5-dinitrosalicylic acid, NO: Nitric oxide, RNS: Reactive nitrogen species,
      PNPG: p-Nitrophenyl-alpha-D-glucopyranoside.

PMID- 29200717
TI  - In vitro and In vivo Activity of Myrsine africana on Elastase Inhibition and Anti
      wrinkle Activity.
AB  - Background: Myrsine africana (MA) is a plant traditionally used in South Africa
      to treat various diseases. Objective: The ethanolic extract of MA, was used for
      in vitro and in vivo studies to determine its elastase inhibitory activity.
      Materials and Methods: MA and its isolated compound, myrsinoside B, were tested
      in vitro for their elastase inhibitory activity. The MA extract was also
      evaluated for mutagenicity using two strains of Salmonella typhimurium (TA 98 and
      TA 100), microbial count, metal analysis, and stability. In vivo studies included
      irritancy and wrinkle reduction trials using Visioscan and Visioface. Results:
      The leaf extract showed good elastase inhibition with a 50% inhibitory
      concentration (IC50) of 28.04 MUg/ml. Myrsinoside B inhibited the elastase enzyme
      at an IC50 of 4.68 +/- 0.34 MUg/ml. No colony growth observed during mutagenicity
      studies and it was concluded that MA ethanolic extract is a nonmutagen. MA
      extract was found to be a nonirritant during the patch test clinical trial. MA
      was found to contain negligible amounts of microorganisms and heavy metals. Gel
      cream containing MA crude extract was found to be stable for 2 years when kept at
      temperatures below 30 degrees C. In clinical trials (in vivo), it was found that
      the test product containing 5% ethanolic extract of MA was effective in reducing
      wrinkles after application 2 times a day for 14 days and 28 days compared to the
      placebo aqueous cream. Conclusion: MA is effective in reducing the appearance of
      wrinkles. SUMMARY: This is a first time report of the elastase inhibitory
      potential of Myrsine africana and myrsinoside B and the anti-wrinkle potential of
      Myrsine africanaMyrsine africana ethanolic extract effectively inhibited the
      elastase enzymeMyrsine africana was effective in in vivo studies to reduce the
      appearance of wrinkles after 14 days. Abbreviations used: 4-NQO: 4
      nitroquinoline, D14-BL: Baseline to day fourteen, D28-BL: Baseline to day twenty
      eight, CFU: Colony forming units, IC50: 50% inhibitory concentration, MA: Myrsine
      africana, MOU: Measurement of uncertainty, NaCl: Sodium chloride, NaH2 PO4.H2O:
      Sodium phosphate monobasic monohydrate, SEM: Standard error of the mean, TA 98:
      Salmonella typhimurium strain 98, TA 100: S. typhimurium strain 100, TLC: Thin
      layer chromatography, TMA: Total microbial activity, XVB salt: Vogel-Bonner
      medium E.

PMID- 29200718
TI  - alpha-Glucosidase Inhibitory Activity from Ethyl Acetate Extract of Antidesma
      bunius (L.) Spreng Stem Bark Containing Triterpenoids.
AB  - Background: Buni (Antidesma bunius [L.] Spreng) has been used as a traditional
      antidiabetic agent in Asia. Objective: The mechanism of antidiabetic properties
      was studied in this study by determine its alpha-glucosidase inhibitory activity.
      Method: Inhibition of alpha-glucosidase was performed in all fraction of Buni
      stem bark with acarbose and miglitol as standards. The half maximal inhibitory
      concentration (IC50) value of acarbose and miglitol was 5.75 and 59.76 MUg/mL
      respectively while ethyl acetate (EtOAc) fraction was the most active fraction
      with IC50 of 19.33 MUg/mL. Three isolates (B1, B2, and B3) were found in the
      EtOAc fraction and elucidated by infrared, 1hydrogen-nuclear magnetic
      resonance,13 carbon-nuclear magnetic resonance, and two-dimensional nuclear
      magnetic resonance. Result: The chemical structures of the isolates were
      identified by the spectrum then compared with literature which concluded that B1
      is friedelin, B2 is beta-sitosterol, and B3 is betulinic acid. Inhibition of the
      alpha-glucosidase assay showed IC50 values of B1, B2, and B3 were 19.51, 49.85,
      and 18.49 MUg/mL, respectively. SUMMARY: alpha-Glucosidase inhibitory activity
      assay was performed in n-hexane, ethyl acetate (EtOAc), methanol fraction of Buni
      (Antidesma bunius (L.) Spreng) stem bark and miglitolEtOAc fraction from the
      liquid chromatography has the highest inhibitory activity against alpha
      glucosidaseThe chemical structures of the isolates were identified by the
      spectrums infrared, 1hydrogen-nuclear magnetic resonance,13 carbon-nuclear
      magnetic resonance, and two-dimensional nuclear magnetic resonance, then compared
      with literature which concluded that B1 is friedelin, B2 is beta-sitosterol, and
      B3 is betulinic acidBetulinic acid and friedelin showed the highest alpha
      glucosidase inhibitory activity. Abbreviations used: IC50: Half maximal
      inhibitory concentration; H-NMR: Hydrogen-nuclear magnetic resonance; C-NMR:
      Carbon nuclear magnetic resonance; 2D-NMR: Two dimensional-nuclear magnetic
      resonance; EtOH: Ethanol; EtOAc: Ethyl acetate; MeOH: Methanol; CHCl3:
      Chloroform; DMSO: Dimethyl sulfoxide; EtF: Ethyl acetate fraction; Na2CO3: Sodium
      carbonate; IR: Infrared; TGR5: Transmembrane G protein-coupled receptor 5; EC50:
      Half maximal effective concentration.

PMID- 29200719
TI  - Anti-cancer Effects of Polyphenolic Compounds in Epidermal Growth Factor Receptor
      Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer.
AB  - Background: Polyphenolic phytochemicals are natural compounds, easily found in
      fruits and vegetables. Importantly, polyphenols have been intensively studied as
      excellent antioxidant activity which contributes to anticancer function of the
      natural compounds. Lung cancer has been reported to mainly account for cancer
      related deaths in the world. Moreover, epidermal growth factor receptor tyrosine
      kinase inhibitor (TKI) resistance is one of the biggest issues in cancer
      treatment, especially in nonsmall cell lung cancer (NSCLC). Even though several
      studies both in preclinical and clinical trials have showed promising therapeutic
      effects of polyphenolic compounds in anticancer therapy, the function of the
      natural compounds in TKI-resistant (TKIR) lung cancer remains poorly studied.
      Objective: The aim of this study is to screen polyphenolic compounds as potential
      anticancer adjuvants which suppress TKIR lung cancer. Materials and Methods:
      Colony formation and thiazolyl blue tetrazolium blue assay were performed in the
      pair-matched TKI-sensitive (TKIS) versus TKIR tumor cell lines to investigate the
      therapeutic effect of polyphenolic compounds in TKIR NSCLC. Results: Our data
      show that equol, kaempferol, resveratrol, and ellagic acid exhibit strong
      anticancer effect in HCC827 panel. Moreover, the inhibitory effect of most of
      tested polyphenolic compounds was highly selective for TKIR lung cancer cell line
      H1993 while sparing the TKIS one H2073. Conclusion: This study provides an
      important screening of potential polyphenolic compounds for drug development to
      overcome TKI resistance in advanced lung cancer. SUMMARY: The study provides an
      important screening of potential polyphenolic compounds for drug development to
      overcome tyrosine kinase inhibitor (TKI) resistance in advance lung cancerEquol,
      kaempferol, resveratrol, and ellagic acid show strong anticancer effect in HCC827
      panel, including TKI-sensitive (TKIS) and TKI-resistant clonesThe inhibitory
      effect of polyphenolic compounds such as equol, kaempferol, resveratrol, ellagic
      acid, gallic acid, p-Coumaric, and hesperidin is highly selective for TKI
      resistant lung cancer cell line H1993 while sparing the TKIS one H2073.
      Abbreviations used: EGFR: Epidermal growth factor receptor, EMT: Epithelial-to
      mesenchymal transition, GTP: Green tea polyphenols, IGF1R: Insulin-like growth
      factor 1 receptor, MET: Met proto-oncogene, MTT: Thiazolyl blue tetrazolium blue,
      NSCLC: Non-small cell lung cancer, ROS: Reactive oxygen species, RTK: Receptor
      tyrosine kinase, STAT3: Signal transducer and activator of transcription 3, TKIR:
      TKI-resistant, TKIs: Tyrosine kinase inhibitors, TKIS: TKI-sensitive.

PMID- 29200720
TI  - Extraction of Chelerythrine and its Effects on Pathogenic Fungus Spore
      Germination.
AB  - Background: Chemical fungicides are widely used to control crop diseases, but
      these chemicals have adverse effects. They destroy the ecological environment and
      even have toxic effects on human beings. In this context, the development of
      botanical pesticides is relevant. One potential botanical pesticide is
      chelerythrine, a main alkaloid of Chelidonium majus L., which has high antitumor,
      fungistasis, and antiphlogosis bioactivity. Objective: This study was designed to
      present an ultrasonic extraction method for chelerythrine and spore germination
      experiments to inhibit pathogenic fungi. Fungistasis of chelerythrine is now
      centralized in basic microbiology experiments, such as observing bacteriostatic
      rings. This study investigates chelerythrine based on pathogenic fungal spore
      germination and the influence of germ tube elongation. Materials and Methods:
      Samples of C. majus L., which were wild used in this experiment, were picked from
      Harbin experimental forest farm of Northeast Forestry University. An L9 (34)
      orthogonal experiment was designed to optimize the ultrasonic extraction method.
      All the plant pathogenic fungus strains used in the experiment were preservation
      strains of Northeast Forestry University Microbial preservation center.
      Pathogenic fungi were cultivated by joining chelerythrine with and observed germ
      tube growth and spore germination. Results: The optimum ultrasonication
      extraction process for chelerythrine has a liquid/solid ratio of 1:8, 35 min of
      extraction time, 85% of ultrasonic frequency, and 75% of ethanol concentration.
      When the concentration of chelerythrine was 1.7 * 10-2 mg/ml, the inhibition
      rates of Septoria microspora Speg. spores and Curvularia lunata were 96.67% and
      84.94%, respectively. Moreover, when the concentration of chelerythrine was 1.7 *
      10-6 mg/ml, the inhibition rates of S. microspora spores and C. lunata were
      47.64% and 12.05%, respectively. Conclusion: Fungistasis activity reached a high
      level with 1.7 * 10-6 mg/ml of chelerythrine. Chelerythrine has the
      characteristics of less dosage and obvious fungistasis and has a good prospect
      for botanical fungicide development. SUMMARY: S. microspora spores in
      chelerythrine concentration of 1.7 * 10-6 mg/ml have an inhibition rate of
      47.64%. For chelerythrine concentrations 1.7 * 10-5, 1.7 * 10-4, and 1.7 * 10-3
      mg/ml, the inhibition rate is 70%, 80%, and 90%, respectively. When the
      concentration of chelerythrine was original 1.7 * 10-2 mg/ml, the inhibition rate
      was 96.67%. As shown in the diagram, the germinal tubes of S. microspora spores
      were shorter than 50 um with 1.7 * 10-6, 1.7 * 10-5, and 1.7 * 10-4 mg/ml
      concentrations of chelerythrine. However, the germinal tubes of spores without
      chelerythrine could reach 80 um. With 1.7 * 10-3 mg/ml liquid concentration, the
      germination was severely inhibited; the germination under concentrate
      chelerythrine was limited. The inhibitory effect of chelerythrine was greatest in
      S. microspora. Abbreviations used:C. majus L.: Chelidonium majus L.; Sphaerulina
      juglandis: S. juglandis; Septoria microspora Speg.: S. microspora; Fusarium
      oxysporum f. sp. Lycopersici: F. oxysporum f. sp. lycopersici; F. oxysporum f.
      cucumerinum: F. oxysporum f. cucumerinum; Curvularia lunata: C. lunata.

PMID- 29200721
TI  - Helichrysetin Induces DNA Damage that Triggers JNK-Mediated Apoptosis in Ca Ski
      Cells.
AB  - Background: Cervical cancer has become one of the most common cancers in women
      and currently available treatment options for cervical cancer are very limited.
      Naturally occurring chalcones and its derivatives have been studied extensively
      as a potential anticancer agent in different types of cancer and helichrysetin is
      naturally occurring chalcone that possess potent antiproliferative activity
      toward human cancer cells. Materials and Methods: Inhibitory activity of
      helichrysetin was evaluated at different concentrations. Ability of helichrysetin
      to induce apoptosis and its relation with c-Jun N-terminal kinase (JNK)-mediated
      mechanism of apoptosis was assessed using flow cytometry and Western blotting.
      Results: Helichrysetin inhibited Ca Ski cells at half maximal inhibitory
      concentration 30.62 +/- 0.38 MUM. This compound has the ability to induce DNA
      damage, mitochondrial membrane disruption, and loss of cell membrane integrity.
      We have shown that apoptosis was induced through the activation of JNK-mediated
      apoptosis by DNA damage in the cells then triggering p53-downstream apoptotic
      pathway with increased expression of pro-apoptotic proteins, Bax and caspase 3,
      and suppression of Bcl-2 anti-apoptotic protein. DNA damage in the cells also
      caused phosphorylation of protein ataxia-telangiectasia mutated, an activator of
      DNA damage response. Conclusion: We conclude that helichrysetin can inhibit Ca
      Ski cells through DNA damage-induced JNK-mediated apoptotic pathway highlighting
      the potential of this compound as anticancer agent for cervical cancer. SUMMARY:
      Helichrysetin induced DNA damage in Ca Ski cellsDNA damage caused JNK-mediated
      phosphorylation of p53 resulting in p53-mediated apoptosisHelichrysetin is a
      potential DNA damage inducing agent through JNK activation to kill human cervical
      carcinoma cells. Abbreviations used: ATM: Ataxia-telangiectasia mutated, DAPI:
      4',6-diamidino-2-phenylindole, DMSO: Dimethyl sulfoxide, FITC: Fluorescein
      isothiocyanate, IC50: Half maximal inhibitory concentration, JC1-5,5',6,6'
      Tetrachloro: 1',3,3'-tetraethylbenzimidazolylcarbocyanine, iodide, JNK: c-Jun N
      terminal kinase, MMP: Mitochondrial membrane potential, PBS: Phosphate-buffered
      saline, SRB: Sulforhodamine B, TUNEL: Terminal deoxynucleotidyl transferase dUTP
      nick labeling.

PMID- 29200722
TI  - In vitro and In vivo Postprandial Glycemic Activity of Citrus limetta Peel Flour.
AB  - Background: Previous studies of Citrus spp. peel have shown hypoglycemic and
      antioxidant activities. Citrus limetta has been studied for its therapeutic
      properties. Diabetes mellitus (DM) is a health problem in Mexico and worldwide,
      that takes a vital importance due to its high incidence. Recently, scientists
      have searched natural sources to control the disease. Materials and Methods: In
      this study, we evaluated the in vitro hypoglycemic activity and in vivo
      postprandial glycemic effect of C. limetta peel flour by glucose adsorption and
      retardation assays as well as postprandial serum glucose levels using a group of
      female Balb-c mice, respectively. Results: C. limetta peel flour showed a glucose
      adsorption capacity of 16.58 mM, having a similar effect regarding the positive
      control. The glucose diffusion in the dialysate was elevated, with a glucose
      dialysis retardation index of 33.79% in a period of 3 h, showing similar results
      to positive control. Postprandial serum glucose levels in the animal group
      treated with C. limetta peel flour showed a glucose level of 41.4 mg/dL, being
      this value significantly lower than negative control group and similar to
      positive control. Toxicity tests showed good tolerance to the dose of 2000 mg/kg.
      Conclusion: C. limetta peel flour could act as a source of functional compounds
      for the control of DM. SUMMARY: Citrus limetta peel flour showed a glucose
      adsorption capacity similar to the positive controlThe glucose diffusion in the
      dialysate was elevated, showing similar results to positive controlPostprandial
      serum glucose levels in the animal group treated with C. limetta peel flour
      showed a glucose level significantly lower than negative control group and
      similar to positive controlToxicity tests showed good toleranceC. limetta peel
      flour could act as a source of functional compounds for the control of diabetes
      mellitus. Abbreviations used: CIATEJ: Center for Research and Assistance in
      Technology and Design of Jalisco; DM: Diabetes mellitus; FGC: Final glucose
      concentration; GDRI: Glucose dialysis retardation index; IGC: Initial glucose
      concentration; OECD: Organization for Economic Cooperation and Development.

PMID- 29200723
TI  - Mice Behavioral Phenotype Changes after Administration of Anani (Symphonia
      globulifera, Clusiaceae), an Alternative Latin American and African Medicine.
AB  - Background: Anani, (Symphonia globulifera, Clusiaceae), known as chewstick, is a
      traditional plant occurring in Africa and in Central and South Americas that is
      used against parasites and microorganisms. Although its use is popular in some of
      these countries, there is a lack of information related to its influence over
      behavioral phenotype (BP). Objective: The objective of this study is to evaluate
      the influence of the administration of the extract obtained from the aerial
      organs of Anani (EB1257) to male Balb-c mice over BP. Materials and Methods: Open
      cage observation, open field, and elevated-plus maze apparatuses were used.
      Evaluations were done 15, 30, 60, 120, and 180 min after intraperitoneal
      administration of Anani extract. Results: Impairment of general behavior
      activity, response to touch, tail squeeze, defecation, locomotion and rearing
      frequency were observed although no signs of hemorrhage or macroscopical
      alterations of internal organs. Anani is harmful, but not toxic if used in the
      appropriate doses, yet to be determined to male mice. Impairment of locomotion
      and defecation was observed, indicating some degree of influence over locomotion,
      but no alterations in anxiety levels were assessed. Three compounds were
      previously found in the plant-lupeol (1), beta-amyrin (2) and 3-beta
      hydroxyglutin-5-ene (3), and one is being described for the first time to occur
      in the species: oleanolic acid (4). Conclusions: The present work contributes in
      the support of the rational use of Anani, an important Latin American and African
      alternative medicine, presenting findings that are being reported for the first
      time. SUMMARY: Symphonia globulifera impairs locomotion and defecatin in behavior
      analysesNo alterations in anxiety was observedOleanolic acid occurs in the
      species. Abbreviations used: BP: Behavioral phenotype; OF: Open field, EPM:
      Elevated-plus maze, MMA/ICMBio/SISBIO: Ministerio do Meio Ambiente/Instituto
      Chico Mendes de Conservacao da Biodiversidade/Sistema de Autorizacao e Informacao
      em Biodiversidade, IBAMA/MMA/CGen: Instituto Brasileiro do Meio Ambiente e dos
      Recursos Naturais Renovaveis/Ministerio do Meio Ambiente/Conselho de Gestao do
      Patrimonio Genetico, AM: Amazonas State, UNIP: Universidade Paulista, mg:
      milligram, kg: kilogram, I.P: Intraperitoneal, CEUA/ICS/UNIP: Comissao de Etica
      no Uso de Animais/Instituto de Ciencias da Saude/Universidade Paulista, LD:
      Lethal dose, NLD: Nonlethal dose, GBA: General behavior activity, FCHCL3:
      Fraction chloroform, FBuOH: Fraction buthanol, FH2O: Fraction water, FrHEX:
      Fraction hexane, FrDCM: Fraction dichloromethane, FrMeOH: Fraction methanol, 13C
      NMR: Carbon nuclear magnetic resonance, EPA: United States Environmental
      Protection Agency.

PMID- 29200724
TI  - Bioassay-guided Isolation of Neuroprotective Fatty Acids from Nigella sativa
      against 1-methyl-4-phenylpyridinium-induced Neurotoxicity.
AB  - Objective: Parkinson's disease, a slowly progressive neurological disease, is
      associated with degeneration of the basal ganglia of the brain and a deficiency
      of the neurotransmitter dopamine. The main aspects of researches are the
      protection of normal neurons against degeneration. Fatty acids (FAs), the key
      structural elements of dietary lipids, are carboxylic straight chains and notable
      parameters in nutritional and industrial usefulness of a plant. Materials and
      Methods: Black cumin, a popular anti-inflammatory and antioxidant food seasoning,
      contains nonpolar constituents such as FAs which were extracted using hexane.
      Different fractions and subfractions were apt to cytoprotection against apoptosis
      and inflammation induced by 1-methyl-4-phenylpyridinium (MPP+) in rat
      pheochromocytoma cell line (PC12) as a neural cell death model. The experiment
      consisted of examination of cell viability assessment, mitochondrial membrane
      potential (MMP), caspase-3 and -9 activity, and measurement of cyclooxygenase
      (COX) activity. Results: MPP+ induced neurotoxicity in PC12 cells. Pretreatment
      with subfractions containing FA mixtures attenuated MPP+-mediated apoptosis
      partially dependent on the inhibition of caspase-3 and -9 activity and increasing
      the MMP. A mixture of linoleic acid, oleic acid, and palmitic acid also decreased
      the COX activity induced by MPP+ in PC12 cells. Conclusion: Our observation
      indicated that subtoxic concentration of FA from Nigella sativa may exert
      cytoprotective effects through their anti-apoptotic and anti-inflammation actions
      and could be regarded as a dietary supplement. SUMMARY: MPP+ induced
      neurotoxicity in PC12 cellsNigella sativa contains bioactive fatty
      acidsPretreatment with fatty acids attenuated MPP+ mediated apoptosis through
      inhibition of caspase 3 and 9 activityA mixture of linoleic acid, oleic acid, and
      palmitic acid decreased the COX activity induced by MPP+ in PC12 cellsDue to
      cytoprotective, anti apoptotic and anti inflammation actions of N. sativa, it
      could be regarded as a dietary supplement. Abbreviations used: ANOVA: Analysis of
      variance; Ca: Calcium; CDCl3: Chloroform; COX: Cyclooxygenase; DMSO: Dimethyl
      sulfoxide; EA: Elidic acid; EDTA: Ethylene diamine tetraacetic acid; ELISA:
      Enzyme Linked Immunosorbent Assay; ESI-MS: Electron spray mass spectroscopy; FAs:
      Fatty acids; FBS: Fetal bovine serum; GC: Gas chromatography; 1HNMR: Hydrogen
      nuclear magnetic resonance; LA: Linoleic acid; MPP+: 1-Methyl-4-phenylpyridinium;
      MPTP: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; MTT: 3-(4,5
      dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide; N. sativa: Nigella sativa;
      OA: Oleic acid; PA: Palmitic acid; PBS: Phosphate buffer saline; PC12: Rat
      pheochromocytoma cell line; PD: Parkinson's disease; PDA: Photo diode array
      detector; PGE2: Prostaglandin E2; TLC: Thin layer chromatography; TMPD: N,N,N',N'
      tetramethyl-p-phenylenediamine; USA: United states of America.

PMID- 29200725
TI  - Ligustilide Relieves Complete Freund's Adjuvant-induced Mechanical Hyperalgesia
      through Inhibiting the Activation of Spinal c-Jun N-terminal Kinase/c-Jun Pathway
      in Rats.
AB  - Background: Ligustilide, an active ingredient in a traditional Chinese medicine,
      has anti-inflammatory and analgesic effects. The underlying mechanisms of the
      anti-inflammatory pain effects of ligustilide are not completely understood.
      Objective: The aim of this study to investigate whether ligustilide conducts its
      analgesic effects on the complete Freund's adjuvant (CFA)-induced inflammatory
      pain through regulating the c-Jun N-terminal kinase (JNK)/c-Jun pathway in the
      spinal cord. Materials and Methods: Paw withdrawal thresholds (PWTs) and paw
      withdrawal latencies (PWLs) were tested to examine the analgesic effect of
      ligustilide on CFA-induced inflammatory pain in rats. The change of spinal JNK/c
      Jun activation was detected by western blotting after CFA injection with or
      without consecutive intrathecal ligustilide administration. After SP600125 (JNK
      inhibitor) was intrathecally injected in CFA rats, PWTs and PWLs were tested to
      investigate the change of ligustilide's analgesic effect. Results: Repeated
      intravenous injection of ligustilide could attenuate the pain hypersensitivity
      induced by CFA. CFA caused increased activation of spinal JNK/c-Jun, which could
      be inhibited by ligustilide administration. Intrathecal injection of JNK
      inhibitor inhibited the CFA-induced mechanical hyperalgesia. Conclusion:
      Ligustilide could inhibit the upregulation of spinal p-JNK/p-c-Jun caused by CFA,
      and the inhibition of JNK/c-Jun activation is closely related to its anti
      mechanical hyperalgesia effect in inflammatory pain. SUMMARY: Ligustilide, an
      active ingredient in a popular traditional Chinese medicine, has effective anti
      inflammatory and analgesic effects. Ligustilide inhibits the complete Freund's
      adjuvant-induced activation of spinal c-Jun N-terminal kinase-(JNK)/c-Jun pathway
      in rats. The inhibition of JNK/c-Jun activation is closely related to the anti
      mechanical hyperalgesia effect of ligustilide. Abbreviations used: CFA: Complete
      Freund's adjuvant, JNK: c-Jun N-terminal kinase, MAPK: Mitogen-activated protein
      kinase, PWT: Paw withdrawal threshold, PWL: Paw withdrawal latency.

PMID- 29200728
TI  - Superoxide Scavenging and Antiglycation Activity of Rhinacanthins-rich Extract
      Obtained from the Leaves of Rhinacanthus nasutus.
AB  - Background: Oxidative stress and nonenzymatic protein glycation lead to serious
      diabetic complications that increase the risk of mortality. Rhinacanthus nasutus
      leaf crude extracts are previously reported for their antidiabetic,
      antiglycation, and antioxidant potential. Objective: The present study was
      performed to prepare a standardized rhinacanthins-rich extract (RRE) and evaluate
      its superoxide scavenging and antiglycation effects as compared to its marker
      compounds, namely, rhinacanthin-C (RC), rhinacanthin-D (RD), and rhinacanthin-N
      (RN). Materials and Methods: RRE was obtained by microwave-assisted green
      extraction along with a simple step of fractionation using Amberlite(r) column.
      RC, RD, and RN were isolated from the RRE using silica gel column chromatography.
      Superoxide scavenging activity was performed by cyclic voltammetry, and fructose
      mediated human serum albumin glycation model was used for antiglycation activity.
      In silico studies were conducted to identify the structure-activity relationships
      of rhinacanthins. Results: On the basis of kinetic measurements, RRE exhibited
      the most potent antioxidant activity via ErCi mechanism, with a 50% inhibitory
      concentration (IC50) value of 8.0 MUg/mL, antioxidant capacity of 39439 M-1, and
      binding constant of 45709 M-1. Antiglycation assay showed that RRE exhibited
      almost equivalent glycation inhibitory effect to that of RC, with IC50 values of
      39.7 and 37.3 MUg/mL, respectively, but higher than that of RD (IC50 of 50.4
      MUg/mL), RN (IC50 of 89.5 MUg/mL), as well as the positive control, rutin (IC50
      of 41.5 MUg/mL). Conclusions: The potent superoxide scavenging and albumin
      glycation inhibitory effect of RRE rationalized its therapeutic application in
      various chronic diseases, especially in the complications of diabetes. SUMMARY:
      Rhinacanthins-rich extract (RRE) exhibited potent superoxide scavenging
      activityRRE and rhinacanthin-C showed remarkable and comparable antiglycation
      effectRhinacanthins exhibited antiglycation activity by masking specific residues
      of albumin. Abbreviations used: RRE: Rhinacanthins-rich extract; RC: Rhinacanthin
      C; RD: Rhinacanthin-D; RN: Rhinacanthin-N; IC50: 50% inhibitory concentration;
      Kao: Antioxidant activity coefficient; Kb: Binding constant; ErCi: Reversible
      electron transfer followed by an irreversible chemical reaction; DM: Diabetes
      mellitus; AGEPs: Advanced glycation end products; NMR: Nuclear magnetic
      resonance; HPLC: High-performance liquid chromatography; CV: Cyclic voltammetry;
      DMSO: Dimethyl sulfoxide; Ipa: Anodic peak current; Ipc: Cathodic peak current;
      HSA: Human serum albumin; MOE: Molecular operating environment; PASSonline:
      Online prediction of activity spectra for substances.

PMID- 29200727
TI  - Antioxidant, Acetylcholinesterase, Butyrylcholinesterase, and alpha-glucosidase
      Inhibitory Activities of Corchorus depressus.
AB  - Background: Corchorus depressus (Cd) commonly known as Boa-phalee belonging to
      the family Tiliaceae having 50 genera and 450 species. Cd is not among the
      studied medicinal agent despite its potential in ethnopharmacology. Objectives:
      The present study investigated antioxidant, acetylcholinesterase (AChE),
      butyrylcholinesterase (BChE), and alpha-glucosidase inhibitory activities of Cd.
      The dichloromethane and methanolic extracts of the Cd were evaluated for
      biological activities such as antioxidant and enzyme inhibitory activities of
      AChE, BChE, and alpha-glucosidase. Materials and Methods: Antioxidant activity
      was evaluated by measuring free radical scavenging potential of Cd using 1,1
      diphenyl-2-picrylhydrazyl. Enzyme inhibition activities were done by measuring
      optical density. Results: The methanol extract of roots of Cd showed potential
      free radical scavenging activity 99% at concentration 16.1 MUg/ml. AChE was
      inhibited by aerial part of dichloromethane fraction by 46.07% +/- 0.45% while
      dichloromethane extracts of roots of Cd possessed significant activity against
      BChE with 86% inhibition compared with standard drug Eserine at concentration 0.5
      mg/ml. The dichloromethane extract of roots of Cd showed 79% inhibition against
      alpha-glucosidase enzyme activity with IC50 62.8 +/- 1.5 MUg/ml. Conclusion:
      These findings suggest Cd as useful therapeutic option as antioxidant and
      inhibition of AChE, BChE, and alpha-glucosidase activities. SUMMARY: The aerial
      parts and roots of Corchorus depressus (Cd) were extracted in dichloromethane and
      methanolThe extract of roots of Cd showed free radical scavenging activity 99% at
      concentration 16.1 mg/ml, Ach inhibition by aerial parts of dichloromethane
      fraction by 46.07%, and 79% inhibition against a-glucosidase enzyme activity with
      IC50 62.8 +/- 1.5 mg/mlThe dichloromethane and methanolic extracts of Cd
      exhibited antioxidant inhibition of acetyl cholinesterase, butyrylcholinesterase,
      and a-glucosidase activities. Abbreviations used: DPPH: 1,1-diphenyl-2
      picrylhydrazyl, Cd: Corchorus depressus, AChE: Acetylcholinesterase, BChE:
      Butyrylcholinesterase, AD: Alzheimer's disease.

PMID- 29200726
TI  - Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.
AB  - Background: The development of alternatives for insulin secretion control in vivo
      or in vitro represents an important aspect to be investigated. In this direction,
      natural products have been progressively explored with this aim. In particular,
      flavonoids are potential candidates to act as insulin secretagogue. Objective: To
      study the influence of flavonoid on overall modulation mechanisms of insulin
      secretion. Methods: The research was conducted in the following databases and
      platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and
      ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones,
      islets of Langerhans, and insulin-secreting cells. Results: Twelve articles were
      included and represent the basis of discussion on mechanisms of insulin secretion
      of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44,
      PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases.
      Conclusion: According to the literature, the majority of flavonoid subclasses can
      modulate insulin secretion through several pathways, in an indication that
      corresponding molecule is a potential candidate for active materials to be
      applied in the treatment of diabetes. SUMMARY: The action of natural products on
      insulin secretion represents an important investigation topic due to their
      importance in the diabetes controlIn addition to their typical antioxidant
      properties, flavonoids contribute to the insulin secretionThe modulation of
      insulin secretion is induced by flavonoids according to different mechanisms.
      Abbreviations used: KATP channels: ATP-sensitive K+ channels, GLUT4: Glucose
      transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L
      VDCCs: L-type voltage-dependent Ca+2 channels, GLUT1: Glucose transporter 1,
      AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine
      phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine
      monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II:
      Ca2+/calmodulin-dependent protein kinase II, GSIS: Glucose-stimulated insulin
      secretion, Insig-1: Insulin-induced gene 1, IRS-2: Insulin receptor substrate 2,
      PDX-1: Pancreatic and duodenal homeobox 1, SREBP-1c: Sterol regulatory element
      binding protein-1c, DMC: Dihydroxy-6'-methoxy-3',5'-dimethylchalcone, GLP-1:
      Glucagon-like peptide-1, GLP-1R: Glucagon-like peptide 1 receptor.

PMID- 29200729
TI  - Rapid Quantitative Analysis of Naringenin in the Fruit Bodies of Inonotus vaninii
      by Two-phase Acid Hydrolysis Followed by Reversed Phase-high Performance Liquid
      Chromatography-ultra Violet.
AB  - Introduction: Sanghuang is one of mystical traditional Chinese medicines recorded
      earliest 2000 years ago, that included various fungi of Inonotus genus and was
      well-known for antitumor effect in modern medicine. Inonotus vaninii is grown in
      natural forest of Northeastern China merely and used as Sanghuang commercially,
      but it has no quality control specification until now. This study was to
      establish a rapid method of two-phase acid hydrolysis followed by reversed phase
      high performance liquid chromatography-ultra violet (RP-HPLC-UV) to quantify
      naringenin in the fruit body of I. vaninii. Materials and Methods: Sample
      solution was prepared by pretreatment of raw material in two-phase acid
      hydrolysis and the hydrolysis technology was optimized. After reconstitution,
      analysis was performed using RP-HPLC-UV. The method validation was investigated
      and the naringenin content of sample and comparison were determined. Results: The
      naringenin was obtained by two-phase acid hydrolysis method, namely, 10.0 g of
      raw material was hydrolyzed in 200 mL of 1% sulfuric acid aqueous solution (v/v)
      and 400 mL of chloroform in oil bath at 110 degrees C for 2 h. Good linearity (r
      = 0.9992) was achieved between concentration of analyte and peak area. The
      relative standard deviation (RSD) of precision was 2.47% and the RSD of
      naringenin contents for repeatability was 3.13%. The accuracy was supported with
      recoveries at 96.37%, 97.30%, and 99.31%. The sample solution prepared using the
      proposed method contained higher content of naringenin than conventional method
      and was stable for 8 h. Conclusion: Due to the high efficiency of sample
      preparation and high reliability of the HPLC method, it is feasible to use this
      method for routine analysis of naringenin in the fungus. SUMMARY: A convenient
      two-phase acid hydrolysis was employed to produce naringenin from raw material,
      and then an efficient and reliable reversed phase-high performance liquid
      chromatography-ultra violet method was established to monitor naringenin in the
      fruit bodies of Inonotus vaninii. The newly established method could be used to
      control the quality of the herb. Abbreviations used: RP-HPLC-UV: Reversed Phase
      High Performance Liquid Chromatography-Ultra Violet, RSD: Relative Standard
      Deviation, EtOAc: Ethyl acetate, ACN: Acetonitrile, MeOH: Methanol, RH: Relative
      Humility.

PMID- 29200730
TI  - Comparative Proteomic Analysis of Three Gelatinous Chinese Medicines and Their
      Authentications by Tryptic-digested Peptides Profiling using Matrix-assisted
      Laser Desorption/Ionization-time of Flight/Time of Flight Mass Spectrometry.
AB  - Background: Gelatinous Chinese medicines (GCMs) including Asini Corii Colla,
      Testudinis Carapacis ET Plastri Colla, and Cervi Cornus Colla, were made from
      reptile shell or mammalian skin or deer horn, and consumed as a popular tonic, as
      well as hemopoietic and hemostatic agents. Misuse of them would not exert their
      functions, and fake or adulterate products have caused drug market disorder and
      affected food and drug safety. GCMs are rich in denatured proteins, but
      insufficient in available DNA fragments, hence commonly used cytochrome c oxidase
      I barcoding was not successful for their authentication. Objective: In this
      study, we performed comparative proteomic analysis of them and their animal
      origins to identify the composition of intrinsic proteins for the first time.
      Materials and Methods: A reliable and convenient approach was proposed for their
      authentication, by the incorporation of sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, two-dimensional electrophoresis, and matrix-assisted laser
      desorption/ionization-time of flight/time of flight mass spectrometry (MALDI
      TOF/TOF-MS). Results: A total of 26 proteins were identified from medicinal parts
      of original animals, and GCMs proteins presented in a dispersive manner in
      electrophoresis analyses due to complicated changes in the structure of original
      proteins caused by long-term decoction and the addition of ingredients during
      their manufacturing. In addition, by comparison of MALDI-TOF/TOF-MS profiling, 19
      signature peptide fragments originated from the protein of GCM products were
      selected according to criteria. Conclusion: These could assist in the
      discrimination and identification of adulterates of GCMs and other ACMs for their
      form of raw medicinal material, the pulverized, and even the complex. SUMMARY:
      Comparative proteomic analysis of three gelatinous Chinese medicines was
      conducted, and their authentications were based on tryptic-digested peptides
      profiling using matrix-assisted laser desorption/ionization-time of flight/time
      of flight mass spectrometry. Abbreviations used: GCMs: Gelatinous Chinese
      medicines, COI: Cytochrome c oxidase I, SDS-PAGE: Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, 2-DE: Two-dimensional electrophoresis, MALDI
      TOF/TOF-MS: Matrix-assisted laser desorption/ionization-time of flight/time of
      flight mass spectrometry, LC: Liquid chromatography, ChP: Chinese Pharmacopoeia,
      HPLC: High performance liquid chromatography, LC-ESI+-MS: Liquid chromatography
      electro spray ionization-mass spectrometry, IEF: isoelectric focusing, HCCA:
      alpha-Cyano-4-hydroxycinnamic acid.

PMID- 29200731
TI  - Brazilian Cerrado Qualea grandiflora Mart. Leaves Exhibit Antiplasmodial and
      Trypanocidal Activities In vitro.
AB  - Background: The rapid spread of drug-resistant strains of protozoan parasites
      required the urgent need for new effective drugs. Natural products offer a
      variety of chemical structures, which make them a valuable source of lead
      compounds for the development of such new drugs. Cerrado is the second largest
      biome in Brazil and has the richest flora of all the world savannahs. We selected
      Qualea grandiflora, a plant species known for its proprieties in folk medicine
      and its antibacterial activity. Objective: However, its antiprotozoal activity
      was not yet explored. Materials and Methods: We investigated the activities of
      fractions from the ethyl acetate extract of Q. grandiflora leaves against human
      life forms of Plasmodium falciparum, Trypanosoma cruzi, and Trypanosoma brucei
      gambiense, and for its cytotoxicity upon the rat L6-myoblast cell line. Ten
      fractions were produced by ethyl acetate:hexane chromatography. Results and
      Conclusion: The fractions showed no cytotoxicity against L-6 cells (IC50 > 100
      MUg/mL) and no hemolysis propriety. Three fractions had a moderate activity
      against P. falciparum, anyone was active against T. cruzi but four fractions
      demonstrated a high activity against bloodstream forms of T. brucei gambiense
      (8.0< IC50 <15 MUg/mL). Identification and characterization of the active
      compounds are currently under investigation. SUMMARY: Qualea grandiflora is an
      endemic tree of the Brazilian Cerrado, which presents medicinal propertiesTen
      fractions of the ethyl acetate extract of Q. grandiflora leaves were assessed
      against Plasmodium falciparum, Trypanosoma Cruzi, and Trypanosoma brucei
      gambienseNo fraction showed relevant cytotoxicity and hemolysis activityAll the
      fractions presented antiplasmodial and trypanocidal activitiesThree fractions
      with moderate antiplasmodial activity (49< IC50 <56 MUg/mL)Four fractions with
      high activity against bloodstream forms of T. brucei gambiense (8.0< IC50 <15
      MUg/mL). Abbreviations used: CQ: Chloroquine, DMSO: Dimethyl sulfoxide, HEPES: 4
      (2-hydroxyethyl)-1-piperazineethanesulfonic acid, HMI: Modified Iscove's medium,
      IC50: Concentration inhibiting 50% of parasite growth, IC90: Concentration
      inhibiting 90% of parasite growth, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide, RPMI: Roswell Park Memorial Institute, SD: Standard
      deviation, SI: Ratio of cytotoxicity to biological activity - TC50/IC50, TC50:
      Concentration causing 50% of cell growth inhibition, TC90: Concentration causing
      90% of cell growth inhibition, TLC: Thin-layer chromatography.

PMID- 29200732
TI  - Two New Phenolic Glycosides from the Aerial Part of Dryopteris erythrosora.
AB  - Background: Dryopteris erythrosora (D.C. Eaton) Kuntze is a species of fern in
      the family of Dryopteridaceae, which is distributed throughout East Asia. The
      genus Dryopteris has been used as traditional medicine, especially to treat
      hepatitis and protect liver. However, only few studies of chemical constituents
      of D. erythrosora have been conducted so far. Objective: In this study, we
      investigated the phytochemical constituents of D. erythrosora. Materials and
      Methods: The 80% methanol extract of the aerial part of D. erythrosora was used
      for the isolation of phenolic compounds. The isolated compounds were elucidated
      by various spectroscopic methods including nuclear magnetic resonance and mass
      spectrometry. Results: The present phytochemical investigation on the aerial part
      of D. erythrosora led to the isolation of two new phenolic glycosides, 1 and 2,
      as well as nine known flavonoids including two flavones (3 and 4) and seven
      flavonols (5-11). Conclusion: In this study, two new phenolic glycosides together
      with nine known flavonoids were isolated from the aerial part of D. erythrosora.
      Among them, compounds 4, 8, and 11 were isolated for the first time in
      Dryopteridaceae family from the present investigation. These results helped us to
      enrich our understanding of the chemical constituents of D. erythrosora and to
      identify compounds 1 and 2 which could be potential chemotaxonomic markers for
      the species. SUMMARY: The genus Dryopteris has been used as traditional medicine,
      especially to treat hepatitis and protect liverTwo new phenolic glycosides were
      isolated from D. erythrosoraNine known flavonoids (3-11) were isolated from D.
      erythrosoraCompounds 4, 8, and 11 were isolated for the first time in
      Dryopteridaceae family. Abbreviations used: HPLC: High-performance liquid
      chromatography; Q-TOF LC/MS: Quadrupole-time-of-flight liquid chromatography/mass
      spectrometry; NMR: Nuclear magnetic resonance; TMS: Tetramethylsilane.

PMID- 29200733
TI  - Amelioration of Intestinal Barrier Dysfunction by Berberine in the Treatment of
      Nonalcoholic Fatty Liver Disease in Rats.
AB  - Objective: To investigate the effect of berberine (BBR) on intestinal barrier
      function in nonalcoholic fat liver disease (NAFLD) in rats. Materials and
      Methods: Rats were divided into three groups: normal diet group (control group
      [CON group]), high-fat diet feeding group (HFD group), and HFD with BBR group.
      After 8 weeks of HFD feeding, rats in the BBR group were given BBR
      intragastrically at a dose of 150 mg/kg daily for 4 weeks. The same volume of
      normal saline was given to the CON and HFD groups. Liver index was detected, and
      Sudan black B staining was used to study fatty degeneration, also the expression
      level of occluding and intestinal flora was analyzed. Results: BBR administration
      significantly reduced HFD-induced increase in body weight (CON group: 379.83 +/-
      61.51 g, HFD group: 485.24 +/- 50.15 g, and BBR group: 428.60 +/- 37.37 g). It
      obviously alleviated the HFD-induced liver fatty degeneration and
      histopathological changes of intestinal mucosa according to liver index low
      density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and total
      cholesterol (P < 0.05). The triglyceride, alanine transaminase, and aspartate
      aminotransferase levels were greatly elevated after BBR treatment (P < 0.05);
      while endotoxin, intestinal fatty acid-binding protein, and tumor necrosis factor
      alpha were significantly reduced (P < 0.05). Moreover, we found that BBR could
      obviously elevate the level of occludin and decrease the level of
      Faecalibacterium prausnitzii and upregulate the level of bacteroides. Conclusion:
      BBR provides significant protection in NAFLD through ameliorating intestinal
      barrier function. SUMMARY: Berberine (BBR), an alkaloid that can be isolated from
      many plants, has been medically used for its wide range of antimicrobial and anti
      inflammatory effectsThis is a study of BBR on liver function and intestinal
      barrier function in nonalcoholic fat liver disease (NAFLD)BBR treatment for NAFLD
      could significantly restore the liver function and provide significant protection
      in NAFLD through ameliorating intestinal barrier function. Abbreviations used:
      BBR: Berberine, NAFLD: Nonalcoholic fat liver disease, ALT: Alanine transaminase,
      AST: Aspartate aminotransferase, TG: Triglyceride, I-FABP: Intestinal-fatty acid
      binding protein, IBD: Inflammatory bowel disease.

PMID- 29200734
TI  - Toxicity and Detoxification Effects of Herbal Caowu via Ultra Performance Liquid
      Chromatography/Mass Spectrometry Metabolomics Analyzed using Pattern Recognition
      Method.
AB  - Background: Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum
      kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful
      joints, and tumors for thousands of years. However, the toxicity of heart and
      central nervous system induced by CW still limited the application. Materials and
      Methods: Metabolomics was performed to identify the sensitive and reliable
      biomarkers and to characterize the phenotypically biochemical perturbations and
      potential mechanisms of CW-induced toxicity, and the detoxification by
      combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao
      (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by
      pattern recognition methods. Results: As a result, the metabolites were
      characterized and responsible for pentose and glucuronate interconversions,
      tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and
      hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose
      metabolism, six networks of which were the same to the metabolic pathways of
      Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was
      also characterized by CW group. The urinary metabolomics also revealed CW-induced
      serious toxicity to heart and liver. Thirteen significant metabolites were
      identified and had validated as phenotypic toxicity biomarkers of CW, five
      biomarkers of which were commonly owned in Aconitum. The changes of toxicity
      metabolites obtained from combinatorial intervention of CG, CB, and CR also were
      analyzed to investigate the regulation degree of toxicity biomarkers adjusted by
      different combinatorial interventions at 6th month. Conclusion: Metabolomics
      analyses coupled with pattern recognition methods in the evaluation of drug
      toxicity and finding detoxification methods were highlighted in this work.
      SUMMARY: Metabolomics was performed to characterize the biochemical potential
      mechanisms of Caowu toxicityThirteen significant metabolites were identified and
      validated as phenotypic toxicity biomarkers of CaowuMetabolite changes of
      toxicity obtained can be adjusted by different combinatorial
      interventions.Pattern recognition plot reflects the toxicity effects tendency of
      the urine metabolic fluctuations according to time after treatment of herbal
      Caowu. Abbreviations used: CW: Caowu (Radix Aconiti kusnezoffii); CHW: Chuanwu
      (Radix Aconiti); TCM: Traditional Chinese Medicine; CG: Caowu and Gancao; CB:
      Caowu and Baishao; CR: Caowu and Renshen; QC: Quality control; UPLC: Ultra
      performance liquid chromatography; MS: Mass spectrometry; PCA: Principal
      component analysis; PLS-DA: Partial least squares-discriminant analysis; OPLS:
      Orthogonal projection to latent structures analysis.

PMID- 29200735
TI  - Therapeutic Effects of Cyathula officinalis Kuan and Its Active Fraction on Acute
      Blood Stasis Rat Model and Identification Constituents by HPLC-QTOF/MS/MS.
AB  - Background: Cyathula officinalis Kuan is widely used in the clinics for the
      treatment of blood stasis in China. Objective: To evaluate the improving blood
      rheology and anti-inflammatory properties of C. officinalis Kuan extract (CO) and
      its active fraction (ACO) on acute blood stasis model Wistar rats and
      characterize the correlative constituents. Materials and Methods: CO at 0.26,
      0.53, and 1.04 g/kg and ACO at 0.38, 0.75, and 1.5 g/kg were administered to
      acute blood stasis model Wistar rats for 3 days. Whole blood viscosity, plasma
      viscosity, and the levels of interleukin-6 (IL-6), nitric oxide (NO), tumor
      necrosis factor alpha (TNF-alpha), and cyclooxygenase-2 (COX-2) in the plasma
      were measured. HPLC-QTOF/MS/MS method was used to identify the major constituents
      of ACO; the properties of two representative components (cyasterone and
      chikusetsusaponin IV) from ACO on thrombin-induced human umbilical vein
      endothelial cells damage model were also assessed by the levels of thromboxane A2
      (TXA2), endothelin (ET), malondialdehyde (MDA), COX-2, endothelial nitric oxide
      synthase (eNOS), and superoxide dismutase (SOD). Results: CO and ACO
      significantly reduced whole blood viscosity, plasma viscosity, and levels of IL
      6, NO, TNF-alpha, and COX-2 in vivo. Forty compounds were identified from ACO,
      mainly as phytoecdysteroids and saponins. Cyasterone and chikusetsusaponin IV
      could significantly inhibit levels of TXA2, ET, MDA, and COX-2 and promote the
      activities of eNOS and SOD in vitro. Conclusion: CO and ACO possessed significant
      improving blood rheology and anti-inflammatory effects on acute blood stasis
      model rats and the representative components Cyasterone and chikusetsusaponin IV
      showed significant anti-inflammatory, antioxidant, and anticoagulant effects in
      vitro. SUMMARY: Cyathula officinalis Kuan is widely used in the clinic for the
      treatment of blood stasis in ChinaThe C. officinalis Kuan extract and the active
      fraction of C. officinalis Kuan (ACO) possessed significant improving blood
      rheology and anti-inflammatory effects on acute blood stasis model ratsForty
      compounds were identified from ACO, mainly as phytoecdysteroids and saponins
      Abbreviations used: TCM: Traditional Chinese Medicine, CO: Cyathula officinalis
      Kuan extract, ACO: Active fraction of Cyathula officinalis Kuan, ROS: Reactive
      oxygen species, IL-6: Interleukin-6, TNF-alpha: Tumor necrosis factor alpha, NO:
      Nitric oxide, COX-2: Cyclooxygenase-2, TXA2: Thromboxane A2, ET: Endothelin, MDA:
      Malondialdehyde, eNOS: Endothelial nitric oxide synthase, SOD: Superoxide
      dismutase, ESI: Electronic spray ionization, ELISA: Enzyme-linked immunosorbent
      assay, HUVECs: Human umbilical vein endothelial cells, DMEM: Dulbecco's modified
      Eagle medium, MMP: Matrix metalloproteinase.

PMID- 29200736
TI  - Induction of Apoptosis by Tithonia diversifolia in Human Hepatoma Cells.
AB  - Background: Traditional Chinese herb Tithonia diversifolia, belonging to the
      Compositae family, has long been applied for the treatment of liver diseases. In
      recent years, many reports also indicated that it possesses hepato-protective,
      anti-inflammatory, and anti-cancer activities. Objective: In this study, we
      evaluated whether T. diversifolia is an effective therapy for hepatocellular
      carcinoma (HCC). Materials and Methods: Dry leaves of T. Diversifolia were first
      extracted in ethyl acetate, then further fractionated by different ratio of n
      hexane-ethyl acetate (8:2->0:1) or methanol as fractions 1-6 (Td-F1 to Td-F6),
      respectively. We first showed that the ethyl acetate extracts of T. diversifolia
      leaves (Td-L-EA) exhibits growth inhibition on human hepatoma HepG2 cells. To
      further check the extracts-induced apoptosis, microscopic observation, fragmented
      chromosomal DNA electrophoresis, apoptotic DNA-detection ELISA assay, flow
      cytometry, and Western blot analysis were performed. Results: After isolating the
      effective fractions from Td-L-EA, we found strong cytotoxic effects of fraction-2
      (Td-F2). By further analyzing the mechanisms of cytotoxic activities using
      microscopic observation, fragmented chromosomal DNA electrophoresis, apoptotic
      DNA-detection ELISA assay, and flow cytometry, we found that induction of
      apoptosis such as DNA fragmentation increased the apoptosis rate and the
      apoptosis sub-G1 populations in Td-F2-treated HepG2 cells. In addition, we also
      confirmed Td-F2-induced degradation of caspase-8, caspase-9, caspase-3, and
      caspase-3 substrate PARP. Besides, Td-F2 also increased the Bcl-2 proapoptotic
      family protein Bax expression. Conclusion: In short, our results clearly showed
      the induction of apoptosis by ethyl acetate extracts of T. diversifolia leaves in
      human hepatoma HepG2 cells, suggesting its potential application as an antitumor
      agent. SUMMARY: T. Diversifolia leaves were first extracted in ethyl acetate,
      then further fractionated by different ratio of n-hexane/ethyl acetate (8:2->0:1)
      or methanol.These extracts exhibit growth inhibition on human hepatoma (HCC)
      HepG2 cells.n-Hexane/ethyl acetate (6:4) extract (Td-F2) induces apoptosis of
      HCC. Abbreviations used:T. diversifolia, Tithonia diversifolia; HCC,
      Hepatocellular carcinoma DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl
      sulfoxide; HRP, horseradish peroxidase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide; OD, optical density; SDS-PAGE, sodium
      dodecylsulfate-polyacrylamide gel electrophoresis; PARP, Poly (ADP-ribose)
      polymerase; PBS, phosphate buffered saline; PI, propidium iodide.

PMID- 29200737
TI  - Hispidulin-7-O-Neohesperidoside from Cirsium japonicum var. ussuriense Attenuates
      the Production of Inflammatory Mediators in LPS-Induced Raw 264.7 Cells and HT-29
      Cells.
AB  - Background: Inflammatory bowel disease (IBD) is characterized by chronic
      inflammation of the gastrointestinal tract and involves secretion of inflammatory
      mediators. The flavone diglycoside hispidulin-7-O-neohesperidoside (HN) isolated
      from the methanolic extract of aerial parts of Cirsium japonicum var. ussuriense,
      but its pharmacologic activities, with the exception of alleviation of alcohol
      toxicity, have not been investigated to date. Objective: The aim of the present
      study was to investigate the anti-inflammatory activities of HN for the treatment
      of chronic inflammatory illnesses, including IBD. Materials and Methods: In
      lipopolysaccharide (LPS)-induced RAW264.7 cells and HT-29 cells, the effects of
      HN on cell viability and nitric oxide (NO) production were examined via MTT assay
      and the Griess reaction, respectively. The expression levels of interleukin (IL)
      1alpha, IL-8, and tumor necrosis factor (TNF)-alpha and inducible nitric oxide
      synthase (iNOS) protein levels were measured by enzyme-linked immunosorbent assay
      and Western blotting, respectively. Results: HN concentration-dependently
      inhibited NO production in LPS-induced RAW 264.7 cells. Treatment with HN
      considerably downregulated the levels of the pro-inflammatory cytokines, IL-1beta
      and TNF-alpha and the iNOS protein level in LPS-induced RAW 264.7 cells.
      Furthermore, HN inhibited the production of the chemotactic cytokine, IL-8, in
      LPS-induced HT-29 cells. Conclusion: HN has potential as an anti-inflammatory
      agent to prevent and/or treat IBD. SUMMARY: Hispidulin-7-O-neohesperidoside (HN)
      is flavone diglycoside isolated from the methanolic extract of aerial parts of
      Cirsium japonicum var. ussuriense.HN concentration-dependently inhibited NO
      production and considerably downregulated the levels of the proinflammatory
      cytokines, IL-1beta and TNF-alpha, and the iNOS protein level in LPS-induced RAW
      264.7 cells.HN inhibited the production of the chemotactic cytokine, IL-8, in LPS
      induced HT-29 cells.HN has potential as an anti-inflammatory agent to prevent
      and/or treat IBD. Abbreviations used: IBD: Inflammatory bowel disease, HN:
      hispidulin-7-O-neohesperidoside, LPS: lipopolysaccharide, NO: nitric oxide, IL:
      interleukin, TNF: tumor necrosis factor, iNOS: inducible nitric oxide synthase,
      CD: Crohn's disease, UC: ulcerative colitis, RT: room temperature, DMEM:
      Dulbecco's modified Eagle's medium, FBS: fetal bovine serum, PBS: phosphate
      buffered saline, SDS: sodium dodecyl sulfate, PVDF: polyvinylidene difluoride,
      SD: standard deviation.

PMID- 29200738
TI  - In Vitro Bioassay-guided Isolation of Radioprotective Fractions from Extracts of
      Pinus koraiensis Bark.
AB  - Objective: The aim of this study was to evaluate radioprotective effect of
      extracts of Pinus koraiensis bark and its fractions on rat splenocytes by using
      bioassay-guided isolation in order to obtain the best active fraction. Materials
      and Methods: P. koraiensis bark was ground and extracted with water, 40% acetone,
      95% ethanol. Bio-guided assay was selected as an evaluation method to further
      fractionate radioprotective component from P. koraiensis bark extract. Total
      phenolic and flavonoid contents in fractions were also measured. Rat splenocytes
      were prepared by using mechanical trituration method. DNA damage was assessed as
      comet parameters (tail DNA%, tail length, tail moment, olive tail moment). The
      levels of malondialdehyde (MDA), and activity of superoxide dismutase (SOD),
      catalase (CAT) in cultured rat splenocytes were also measured. Results: The
      radioprotective effects decreased from rutin >95% ethanol extracts of Pinus
      koraiensis bark (95EEP) >40AEP > WEP. The stimulating effects decreased from
      rutin > n-butanol extract (NBE) > EAE. The results demonstrate that there exists
      toxic ingredients (PEE and dichloromethane extract), proliferative-promoting,
      radioprotective component (EAE and NBE) in 95EEP. fraction eluted from n-butanol
      fractions of 95EEP with 50% methanol solution (NBEPKB-50ME), a fraction of NBE
      result from bio-guided isolation, demonstrates good radioprotective efficacy on
      rat splenocytes. NBEPKB-50ME pretreated rat splenocytes demonstrated
      progressively reduced levels of MDA when compared with gamma-ray exposed cells.
      Different dose of NBEPKB-50ME pretreatment with 8 Gy-irration showed an increase
      in enzymatic antioxidant. Conclusions: Proliferative-promoting efficacy,
      radioprotective effect of different solvents extracts of the bark of P.
      koraiensis were investigated in this work. NBEPKB-50ME was the best elution in
      NBE, especially in restoring SOD, CAT activities, content of GSH, decreasing DNA
      damage. SUMMARY: The radioprotective effects decreased from rutin > 95EEP > 40AEP
      > WEP. The extract of Petroleum ether, dichloromethane extract (DME) of 95%
      ethanol extract of P. koraiensis (PEE, DME) show toxic effect on rat splenocytes.
      The extract of Ethyl acetate, n-butanol extract of 95% ethanol extract of P.
      koraiensis (EAE, NBE) show proliferative-promoting, radioprotective effect on rat
      splenocytesSingle-cell gel electrophoresis was used to evaluate the spleen cell
      DNA damage parameters affected by gamma-radiation and addition of best component
      NBEPKB-50Me from extract of P. koraiensis barkNBEPKB-50ME pretreatment with 8 Gy
      irradiation showed an increase in enzymatic antioxidant capacity. NBEPKB-50ME
      pretreated (80, 160, 320, 480 mg/ml) rat splenocytes demonstrated progressively
      reduced levels of MDA when compared with g-ray exposed cells. Abbreviations used:
      MDA: Malondialdehyde; SOD: Superoxide dismutase; CAT: Catalase; PEE: Petroleum
      ether Extract; DME: Dichloromethane extract; EAE: Ethyl acetate extract; NBE: n
      butanol extract; WAP: Water extracts of Pinus koraiensis bark; 40AEP: 40% acetone
      extracts of Pinus koraiensis bark; 95EEP: 95% ethanol extracts of Pinus
      koraiensis bark; TPC: Total phenolic content; TFC: Total flavonoid content;
      NBEPKB-50ME: Fraction eluted from n-Butanol fractions of 95EEP with 50% methanol
      solution.

PMID- 29200739
TI  - A Study of the Anti-Cancer Effects of the Hexane Fraction of the Methanol Extract
      of Forsythiae Fructus.
AB  - Background: Forsythiae Fructus (FF) is a well-known medicinal herb derived from
      the dried fruits of Forsythia suspensa (Thunb.) Vahl. (Oleaceae). Recently,
      bioactive compounds isolated from hydrophobic solvent fractions of FF have been
      reported to have anti-oxidant, antibacterial, and anti-cancer effects. Objective:
      Almost all herbal medicines are derived from water extracts, which suggests
      different extraction methods might enhance the practical efficacies of herbal
      medicines. In this study, the authors further investigated the most potential
      anti-cancer fraction, that is, the hexane fraction (FFH) of the methanol extract
      (FFM) of the dried fruits of Forsythia suspensa. Materials and Methods: FFH was
      investigated by measuring its effects on the viability and apoptotic death of PC
      3 cells (a prostate cancer cell line), on the expression levels of Bcl-2, Bax,
      cytochrome c, procaspase-9, procaspase-3 and PARP, and caspase-3 activity.
      Results: FFH significantly accelerated apoptotic cell death and decreased the
      protein levels of Bcl-2, procaspase-9, and procaspase-3. Conclusion: FFH can act
      as a pro-oxidative agent and induce the apoptosis of prostate cancer cells.
      SUMMARY: Hexane fraction of the methanol extract of Forsythiae Fructus (FFH) at a
      concentration more than 50 ug/mL significantly reduced PC-3 cell viabilityFFH
      time and dose dependently elevated intracellular ROS levels and increased the
      proportion of cells arrested in the G0/G1 phaseFFH significantly accelerated
      apoptotic cell death and diminished the protein expression levels of Bcl-2,
      procaspase-9, and procaspase-3The protein expression levels of Bax, cytochrome c,
      and cleaved PARP were increased by FFH, and so was the caspase-3 activity.
      Abbreviations used: FF: Forsythiae Fructus; FFM: Methanol extract of Forsythiae
      Fructus; FFH: Hexane fraction of the methanol extract; DCFH-DA: 2',7'
      dichlorodihydro-fluorescein diacetate.

PMID- 29200740
TI  - Evaluation of Hypolipidemic and Antioxidant Effects in Phenolrich Fraction of
      Crataegus pinnatifida Fruit in Hyperlipidemia Rats and Identification of Chemical
      Composition by Ultra-performance Liquid Chromatography Coupled with Quadropole
      Time-of-flight Mass Spectrometry.
AB  - Background: Hawthorn (Crataegus pinnatifida) fruit has enjoyed a great popularity
      as a pleasant-tasting food associated with hypolipidemic and antioxidant effects.
      Objective: Our aim was to screen the effective fraction of hawthorn fruit in the
      treatment of hyperlipidemia rats. Materials and Methods: In this study, ethanol
      extract of hawthorn fruit (Fr.1) and four fractionated extracts (Fr.2, Fr.3,
      Fr.4, and Fr.5) were compared to total phenol content evaluated using Folin
      Ciocalteu method, and hypolipidemic and antioxidant effects were assessed in
      hyperlipidemic rats. Results: Total phenol content of Fr.4 was higher than other
      fractions by at least 2 fold. Furthermore, this fraction possessed the strongest
      hypolipidemic and antioxidant effects in hyperlipidemic rats. On this basis, 15
      phenolic compounds and four organic acids in Fr.4 were positively or tentatively
      identified using ultra-performance liquid chromatography coupled with quadropole
      time-of-flight mass spectrometry. In addition, 5-O-caffeoyl quinic acid butyl
      ester was first reported in hawthorn fruit. Conclusion: Phenol-rich fraction in
      hawthorn fruit exhibited satisfactory hypolipidemic and antioxidant effects, and
      this could be exploited for further promotion of functional foods. SUMMARY:
      Phenol-rich fraction in hawthorn fruit possesses most potent hypolipidemic and
      antioxidant effects in hyperlidemia rats. Abbreviations used: UPLC-Q-TOF-MS/MS:
      Ultra performance liquid chromatography coupled with quadropole time-of-flight
      mass spectrometry; TC: Total cholesterol; TG: Triglyceride; LDL-C: Low-density
      lipoprotein-cholesterol; HDL-C: High-density lipoprotein-cholesterol; GSH-Px:
      Glutathione peroxidase; SOD: Superoxide dismutase; MDA: Malondialdehyde; CAT:
      Catalase; NO: Nitric oxide; NOS: Nitric oxide synthase; ROS: Reactive oxygen
      species; *OOH: Superoxide anions, *OH: Hydroxyl radicals.

PMID- 29200741
TI  - Enzyme Inhibitors Cause Multiple Effects on Accumulation of Monoterpene Indole
      Alkaloids in Catharanthus Roseus Cambial Meristematic Cell Cultures.
AB  - Background: Enzyme inhibitors have been used for the clarification of
      biosynthesis of natural products. Catharanthus roseus cambial meristematic cell
      (CMC) culture has been established and proved to be a better monoterpeneindole
      alkaloid (MIA) producer than C. roseus dedifferentiated cell (DDC) culture.
      However, little is known about the inter-relationship of the MIA-biosynthetic
      genes with respect to their transcription. Objective: To clarify effects of
      alteration of one gene transcription on transcript levels of another genes in MIA
      biosynthetic pathway, and how the accumulation of MIAs in CMCs are influenced by
      the alteration of their biosynthetic gene transcript levels. Materials and
      Methods: 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor lovastatin and
      1-deoxy-D-xylulose 5-phosphate synthase (DXS) inhibitor clomazone were fed to C.
      roseus CMC cultures. The contents of MIAs were qualified by High Performance
      Liquid Chromatography and the transcript levels of the relevant genes were
      measured by qRT-PCR. Results: Lovastatin improved the accumulation of MIAs via
      increasing the transcription of their biosynthetic genes encoding DXS1,
      tryptonphan decarboxylase (TDC), loganic acid methyltransferase (LAMT),
      strictosidine synthase (STR), desacetoxyvindoline-4-hydroxylase (D4H) and ORCA3
      (a jasmonate-responsive transcriptional regulator), whereas clomazone reduced the
      contents of MIAs and the mRNA levels of the corresponding genes. Conclusion: The
      biosynthesis of MIAs in C. roseus is is manipulated via a complex mechanism, the
      knowledge of which paves the way for rationally tuning metabolic flux to improve
      MIA production in C. roseus CMCs.

PMID- 29200742
TI  - Contribution of the Glucosinolate Fraction to the Overall Antioxidant Potential,
      Cytoprotection against Oxidative Insult and Antimicrobial Activity of Eruca
      sativa Mill. Leaves Extract.
AB  - Background: Eruca sativa Mill. (Brassicaceae) is commonly utilized as an
      ingredient in salads and also as a folk remedy to treat various diseases.
      Objective: The objective of this study was to establish the contribution of the
      glucosinolate (GLS) fraction to the overall antioxidant, cytoprotection against
      oxidative insult and antimicrobial properties of the hydro-alcoholic extract of
      E. sativa leaves from Sicily (Italy), characterized phytochemically. Materials
      and Methods: The antioxidant activity was evaluated by different in vitro
      systems. The cytoprotective effect against hydrogen peroxide (H2O2)-induced
      oxidative stress was tested in human peripheral blood mononuclear cells (PBMCs).
      The antimicrobial potential against bacteria and fungi was assayed by standard
      methods. Results: E. sativa extract exhibited both radical scavenging (50%
      inhibitory concentration [IC50] 1.04 +/- 0.04 mg/mL) and ferrous ions-chelating
      activity (IC50 0.327 +/- 0.0032 mg/mL) and mild reducing power; the GLS fraction
      showed chelating ability only (IC50 0.225 +/- 0.009 mg/mL). In the experimental
      model of H2O2-induced oxidative stress in human PBMCs, a significant
      cytoprotective effect and a suppression of reactive oxygen species production by
      both extract and GLS fraction were observed (P < 0.001). E. sativa extract
      displayed moderate antimicrobial activity against Gram-positive bacteria, and
      Staphylococcus aureus was the most sensitive strain (minimum inhibitory
      concentration 0.125 mg/mL), whereas the GLS fraction was not active. Conclusion:
      GLSs are not involved in the primary antioxidant activity of E. sativa leaf
      extract but they are, almost in part, responsible for its ferrous ion-chelating
      properties. Iron-chelating compounds in E. sativa extract may protect cells under
      conditions of oxidative stress, and GLSs might play a chief role in this effect.
      SUMMARY: Eruca sativa Mill. leaf extract exhibited antioxidant activity in
      different in vitro systems, whereas the glucosinolate (GLS) fraction showed Fe2+
      chelating ability onlyA significant cytoprotective effect and a suppression of
      intracellular reactive oxygen species production by both extract and GLS fraction
      were observed in human peripheral blood mononuclear cellsE. sativa extract
      displayed moderate antimicrobial activity against Gram-positive bacteria, whereas
      the GLS fraction was not active. Abbreviations used: GLS: Glucosinolate; H2O2:
      Hydrogen peroxide; PBMCs: Peripheral blood mononuclear cells; IC50: 50%
      inhibitory concentration; MIC: Minimum inhibitory concentration.

PMID- 29200744
TI  - Potential of Ayurveda - An eye opener.

PMID- 29200743
TI  - Can We Advance Macroscopic Quantum Systems Outside the Framework of Complex
      Decoherence Theory?
AB  - Macroscopic quantum systems (MQS) are macroscopic systems driven by quantum
      rather than classical mechanics, a long studied area with minimal success till
      recently. Harnessing the benefits of quantum mechanics on a macroscopic level
      would revolutionize fields ranging from telecommunication to biology, the latter
      focused on here for reasons discussed. Contrary to misconceptions, there are no
      known physical laws that prevent the development of MQS. Instead, they are
      generally believed universally lost in complex systems from environmental
      entanglements (decoherence). But we argue success is achievable MQS with
      decoherence compensation developed, naturally or artificially, from top-down
      rather current reductionist approaches. This paper advances the MQS field by a
      complex systems approach to decoherence. First, why complex system decoherence
      approaches (top-down) are needed is discussed. Specifically, complex adaptive
      systems (CAS) are not amenable to reductionist models (and their master
      equations) because of emergent behaviour, approximation failures, not accounting
      for quantum compensatory mechanisms, ignoring path integrals, and the subentity
      problem. In addition, since MQS must exist within the context of the classical
      world, where rapid decoherence and prolonged coherence are both needed. Nature
      has already demonstrated this for quantum subsystems such as photosynthesis and
      magnetoreception. Second, we perform a preliminary study that illustrates a top
      down approach to potential MQS. In summary, reductionist arguments against MQS
      are not justifiable. It is more likely they are not easily detectable in large
      intact classical systems or have been destroyed by reductionist experimental set
      ups. This complex systems decoherence approach, using top down investigations, is
      critical to paradigm shifts in MQS research both in biological and non-biological
      systems.

PMID- 29200745
TI  - Ayurveda: Science of life, genetics, and epigenetics.
AB  - Ayurveda is a traditional system of medicine originated in the ancient Vedic
      times of India. This body of knowledge is found in well-documented texts such as
      the Charaka Samhita and Sushruta Samhita, and describes physiology and
      interrelated systems of the body, variations in human constitution, surgery,
      herbal use, and health-promoting recommendations. Ayurveda is translated as the
      "Science of Life;" Ayus = Life, and Veda = knowledge/science. The principles and
      treatment modalities have endured over time. For Ayurveda to be appreciated by
      Western medical researchers, this traditional system of medicine needs to be
      understood in terms of modern science. The current theories of physiology that
      support Ayurvedic approaches need to be explored. Herein, one approach of how the
      realm of epigenetics can help elucidate the mechanisms of Ayurveda has been
      described.

PMID- 29200746
TI  - Salacia - The new multi-targeted approach in diabetics.
AB  - Salacia species plant has been used traditionally as an Ayurvedic medicine for
      diabetes mellitus. Studies over the past decades have shown its multi-targeted
      role in diabetics. In the present review article, various mechanisms of action of
      Salacia on diabetics are discussed in detail. Apart from the well-known action of
      decreasing postprandial glucose sugar by inhibiting alpha-glucosidase and alpha
      pancreatic amylase, it also inhibits aldose reductase which otherwise results in
      microvascular complications. Importantly, its peroxisome proliferator-activated
      receptor (PPAR)-gamma agonist (such as thiazolidinediones, the insulin
      sensitizers) action increases the uptake of free fatty acid (FFA) and facilitates
      their storage in subcutaneous fat rather than the visceral fat. This reduces
      plasma FFA and insulin resistance. Furthermore, it increases the expression of
      and translocation to the cell surface of glucose transporter 1 and 4 receptors
      which result in glucose uptake by the liver and skeletal muscle and decreases
      plasma glucose levels. It also decreases inflammatory cytokines and increases
      adiponectin expression. Salacia as PPAR-alpha agonist (such as fibrates) has a
      role in the management of dyslipidemia. The activation of PPAR-alpha leads to the
      increased expression of lipoprotein lipase and apolipoprotein (Apo) A-V and
      decrease in hepatic Apo-C-III. These actions lower plasma triglycerides in
      chylomicrons and very low-density lipoprotein particles, thus liberating fatty
      acids, which are taken up and stored as fat in adipocytes. Salacia has been shown
      to suppress the overexpression of cardiac PPAR-alpha (similar to angiotensin
      converting enzyme inhibitors/angiotensin receptor blockers) and thereby
      preventing diabetic cardiomyopathy. It also suppresses the cardiac angiotensin II
      Type 1 receptors resulting in antihypertrophic and antifibrogenic effect.

PMID- 29200748
TI  - Clinical evaluation of efficacy of Alambushadi Ghana Vati and Vaitarana Basti in
      the management of Amavata with special reference to rheumatoid arthritis.
AB  - The clinical presentation of Amavata closely mimics with the special variety of
      rheumatologic disorders called rheumatoid arthritis (RA). The Ayurvedic approach
      toward the treatment of Amavata is the need of present era as no system is
      successful in providing the complete cure to this disease. Amavata is a
      challenging and a burning problem of medical science. Prevalence of RA is
      approximately 0.8% of the population. Due to wide spectrum of disease, much
      prevalence in the society, and lack of effective medicine, the disease had been
      chosen for the study. The aim of the research was to study the efficacy of
      Alambushadi Ghana Vati and Vaitarana Basti in the management of Amavata (RA). It
      was a single-center, randomized, open-clinical study. In the present study, 30
      clinically diagnosed patients of Amavata were selected and randomly divided into
      two groups by lottery method. Alambushadi Ghana Vati was given in dose of two
      tablets (each 500 mg) three times in a day with lukewarm water after meal for 30
      days, while Vaitarana Basti on alternate day (15 Basti) had been given
      simultaneously in the second group along with drug of first group. Statistical
      analysis was done using InStat GraphPad 3 Software. Wilcoxon matched pairs signed
      ranks test was used for the analysis of nonparametric data, while paired t-test
      was used for parametric data analysis and Mann-Whitney test and unpaired t-test
      were used for intergroup comparison. Statistically highly significant (HS)
      improvement was found in erythrocyte sedimentation rate, and HS results were
      found in symptoms of Amavata when the Vaitarana Basti was used along with
      Alambushadi Ghana Vati. With excellent relief in 20% patients, significant relief
      in 60% patients, moderate relief in 13.33% patients, whereas mild relief in 6.66%
      patients. On comparing the effect of two therapies, it can be concluded that
      Group B (Alambushadi Ghana Vati and Vaitarana Basti) provided better relief than
      Group A (Alambushadi Ghana Vati) in most of the sign and symptom of the disease
      at significant level.

PMID- 29200747
TI  - Dhatakyadi Varti - An effective local treatment for Upapluta Yonivyapad
      (vulvovaginitis during pregnancy): A standard controlled randomized clinical
      trial.
AB  - Background: Pregnant women are more prone to vulvovaginitis which is a great
      challenge for obstetricians today. In Ayurveda, Upapluta Yonivyapad described by
      Acharya Charaka, Sharangadhara, and both Vagbhata can be compared to
      vulvovaginitis during pregnancy. Aims: The present study aimed to evaluate
      efficacy of Dhatakyadi Varti in the management of Upapluta Yonivyapad
      (vulvovaginitis during pregnancy). Materials and Methods: A total of 80 female
      patients in the age group of 19-40 years were registered and divided into two
      groups. In Group A (n = 46), Dhatakyadi Varti was inserted intravaginally, and in
      Group B (n = 34), Clingen vaginal suppository was inserted intravaginally once at
      bed time for 14 days. The effect of therapy was assessed on the basis of relief
      in subjective and objective criteria, i.e., vaginal smear test. Results: In
      subjective parameters, such as Yoni Srava, Yoni Kandu, Yoni Vedana, Yoni Daha and
      Yoni Daurgandhya, better result was observed in trial Group A receiving
      Dhatakyadi Varti. Highly significant relief (P < 0.001) was observed in fungal
      infection, and significant relief (P = 0.005) was observed in Gram - negative
      bacterial infection and pus cells in Group A. In Group A, 34.88% patients had
      complete remission, marked improvement was found in 34.88% cases, and only 2.32%
      patients remained unchanged, while in Group B, 33.33% patients reported complete
      remission, marked improvement was found in 10% cases, and 20% patients remained
      unchanged. Conclusion: It was concluded from the clinical trial that Dhatakyadi
      Varti is highly effective in reducing subjective and objective variables of
      Upapluta Yonivyapad and can be introduced as a safe herbal therapy of vaginal
      discharge during pregnancy.

PMID- 29200749
TI  - Role of Virechana and Ashwatha Phala Churna in the management of Ksheena Shukra
      (oligozoospermia): A pilot study.
AB  - Background: Infertility is the inability of a sexually active, noncontracepting
      couple to achieve spontaneous pregnancy in 1 year. Low sperm count
      (oligozoospermia) is one of the main causes of male infertility and is correlated
      with Ksheena Shukra (oligozoospermia). Shodhana procedures are to be performed
      before the administration of Vajikarana drugs, especially Virechana Karma has
      been indicated in the cases of Shukra Dushti. The fruit of Ashwatha (Ficus
      religiosa Linn.) has been indicated in premature ejaculation and low sperm count.
      Aim: This study aimed to evaluate the effect of Virechana and Ashwatha Phala
      Churna in the management of Ksheena Shukra (oligozoospermia). Materials and
      Methods: Eligible male participants between the age of 21 and 50 years, with
      sperm count <15 million/ml, received Ashwatha Phala Churna for 60 days in the
      dose of 3 g, after undergoing Virechana Karma. The primary outcomes measured were
      percentage changes in the seminal parameters and associated symptoms of Ksheena
      Shukra in comparison to baseline. Results: The Ashwatha Phala Churna administered
      after Virechana provided 59.78% increase in sperm count, 36.81% increase in semen
      volume, and 16.18% decrease in abnormal form of sperm and 91.34% of increase was
      reported in total sperm count after Virechana Karma which was also statistically
      significant. Conclusion: Overall assessment of the therapy showed that
      administration of Ashwatha Phala Churna after performing Virechana provided
      statistically significant improvement on seminal parameters, especially total
      sperm count.

PMID- 29200750
TI  - A comparative study of Shilajatu and Asanadi Ghana Vati in the management of
      Madhumeha w.s.r. to type-2 diabetes mellitus.
AB  - Introduction: Diabetes mellitus is becoming an alarming problem for society
      nowadays causing impediment in normal life. Diabetes and its complications impose
      a major burden upon health-care facilities. Materials and Methods: In this study,
      90 patients of Madhumeha (type-2 diabetes mellitus) were registered and randomly
      divided into two groups. Out of 90 registered patients, 80 patients completed the
      treatment. In Group A, cap. Shilajatu (500 mg twice daily) was given for 3 months
      and in Group B, Asanadi Ghana Vati (2 Vati twice daily) was given for 3 months.
      Aim: An attempt was made to evaluate and compare the efficacy of Shilajatu and
      Asanadi Ghana Vati in the management of type-2 diabetes mellitus. The efficacy of
      therapy was assessed on the basis of improvement in sign and symptoms of diabetes
      mellitus, blood sugar level, and glycosylated hemoglobin. Results: Statistically
      significant improvement was observed in sign and symptoms as well as on blood
      sugar level in both groups after the completion of treatment. Conclusion:
      Shilajatu and Asanadi Ghana Vati seem to be effective and completely safe for the
      management of Madhumeha (type-2 diabetes mellitus).

PMID- 29200751
TI  - Adjuvant effect of Chakshushya Rasayana with beta-blocker eye drops in the
      management of progressive glaucomatous optic neuropathy: An open-label randomized
      controlled trial.
AB  - Introduction: Primary open angle glaucoma is an insidious and chronic vision
      threatening eye ailment due to neuro-retino-optic nerve degeneration, which may
      be due to the raised intraocular pressure (IOP) or due to independent factors.
      Management of glaucoma is mainly concentrated on lowering IOP that requires
      lifetime topical medication, different ocular medicaments for lowering of IOP,
      and surgical interventions, but it has its own limitations to control the
      progression of glaucomatous optic neuropathy (GON), and this is the reason behind
      the use of alternative neuroprotective adjuvants. Aim: To evaluate the
      neuroprotective effect of Ayurvedic line of management of progressive GON.
      Materials and Methods: Ingredients of trial drug Vara Fort powder (Chakshushya
      Rasayana) were procured from the Institute Pharmacy, except Swarnamakshika
      Bhasma, which was purchased from Dhootapapeshwar Pharmaceuticals. The patients
      fulfilling inclusion criteria, attending outpatient and inpatient departments,
      irrespective of their sex, race, religion, occupation, etc., were selected and
      divided into two groups with open-labeled randomization. In Group A, in addition
      to betaxolol (0.1%) or timolol (0.5%) (non-iobrim), Chakshushya Rasayana 6 g/day
      orally with Triphala Ghrita and honey along with Koshtha-Shuddhi (body
      microchannel clearing treatment) protocol was tried. Nasya (oleation through
      nasal route) with Jeevantyadi Taila and Tarpana (eye satiation) with Go-Ghrita
      were also performed. In Group B (control), brimonidine (iobrim) 0.2% eye drop was
      used for 3 months. Results: Significant improvement was observed in subjective
      parameters in Group A such as blurred vision, frequent change of presbyopic
      glasses, and delayed dark adaptation. Conclusion: Chakshushya Rasayana, if
      administered in a systematic approach along with a modern topical betaxolol or
      timolol eye drops, has a definite role in improving the lost retinal sensitivity
      as much as up to 12 dB in 3 months duration.

PMID- 29200752
TI  - Simultaneous determination of vasicine and vasicinone by High-performance liquid
      chromatography in roots of eight Sida species.
AB  - Introduction: Sida L. is a medicinally important genus widely used in
      conventional systems of medicine in India. Aim: The present study aims toward
      simultaneous determination of two bioactive compounds vasicine and vasicinone in
      root extracts of eight Sida spp. from Western Ghats, India. Materials and
      Methods: Determination of vasicine and vasicinone was undertaken in methanolic
      root extracts (10% w/v) of Sida acuta, Sida cordata, Sida cordifolia, Sida
      rhombifolia, Sida spinosa, Sida indica, Sida retusa and Sida mysorensis by high
      performance liquid chromatography (HPLC) method. The standards were prepared with
      the concentration of mg/mL. Data were expressed as mean values of three reading
      and relative standard deviations. The separation was achieved on a Waters, Nova
      Pack, C18 (250 mm * 4.6 mm, 5 MU) column, with acetonitrile - 0.1 M phosphate
      buffer-glacial acetic acid (15: 85: 1, v/v/v) as solvent system at a flow-rate of
      1.0 mL/min. The effluent was monitored using ultraviolet detection at a
      wavelength of 300 nm. Results: Both calibration curves of standard showed good
      linear regression (R2 > 0.994). The limit of detection and the limit of
      quantification for vasicine was 0.110 and 0.333 MUg/mL and for vasicinone was
      0.059 and 0.179 MUg/mL respectively. The vasicine content was highest in S.
      cordifolia (9.891 +/- 0.495 MUg/100 mg) and vasicinone content was rich in S.
      cordata (33.013 +/- 1.651 MUg/100 mg.) The content of vasicinone was higher than
      vasicine. Conclusion: HPLC method provides simple, accurate, and reproducible
      quantitative analysis for simultaneous determination of vasicine and vasicinone.
      Among the selected Sida species, S. cordifolia and S. cordata were found to be
      rich in the vasicine and vasicinone contents, respectively.

PMID- 29200753
TI  - Evaluation of analgesic and antipyretic activities of Mahanimba (Melia azedarach
      Linn.) leaf and root powder.
AB  - Introduction: Mahanimba (Melia azedarach Linn.) is a deciduous tree of family
      Meliaceae and its root is mainly used in painful condition such as Gridhrasi
      (sciatica) in Ayurveda. Ethnomedicinal claims indicate that its leaves are used
      to treat fever, but its medicinal activities have not been proven by research.
      Aim: This study was aimed to evaluate the potential analgesic and antipyretic
      activities of M. azedarach L. leaf powder (MLP) and M. azedarach L. root powder
      (MRP). Materials and Methods: The root and leaves of M. azedarach were made into
      powder using guidelines mentioned in the Ayurvedic Pharmacopoeia of India. The
      analgesic activity of the test drugs was evaluated against acetic acid-induced
      writhing test in mice and radiant heat-induced pain in albino rats, and
      antipyretic activity was evaluated against Brewer's yeast-induced pyrexia using
      Charles Foster rats. Results: In acetic acid induced writhing in mice, the test
      drugs MRP (1.3mg/kg) exhibit insignificant reduction in writhing reflex while MLP
      (1.3mg/kg) did not show any significant effect in comparison to the control
      group. MRP showed mild-to-moderate insignificant increase in latency of
      withdrawal response at 60 (26.74%) and 120 min (27.25%), while MLP did not show
      central analgesic effect in radiant heat model in rats. MRP showed a significant
      reduction in rectal temperature after 3 and 6 h, while MLP-treated group showed
      significant reduction after 6 h. Conclusion: MRP has mild-to-moderate peripheral
      and central analgesic effects, while MLP has not shown significant analgesic
      effects in both the experimental models. MRP has more pronounced antipyretic
      effect compared to MLP.

PMID- 29200754
TI  - Evaluation of glucose utilization capacity of bioactivity-guided fractions of
      Barleria prionitis Linn and Hyptis suaveolens (L.) Poit in isolated rat
      hemidiaphragm.
AB  - Introduction: Diabetes mellitus (DM) is a chronic disease characterized by high
      blood glucose levels due to absolute or relative circulating insulin levels.
      Plants represent a major potential source of drugs for treating diabetes. The
      study of plants having antidiabetic activity may give a new approach in the
      treatment of DM. Aim: This study was aimed to investigate the glucose utilization
      capacity of bioactivity-guided fractions of Barleria prionitis and Hyptis
      suaveolens. Materials and Methods: The dried coarse powdered plant material was
      extracted in aqueous ethanol by cold maceration; further, ethanolic extracts were
      fractionated using solvents of varying polarity and were investigated in isolated
      rat hemidiaphragm using 0.1% and 0.2% concentrations of plant extracts. Results:
      The tested fractions of both plants showed significant and dose-dependent
      increased glucose uptake capacity and was found to be maximum with petroleum
      ether and aqueous ethanolic extracts of both plants; 0.2% concentration of both
      plant extracts is superior in activity when compared to 0.1% of the test
      extracts. H. suaveolens has produced more glucose utilization capacity when
      compared to B. prionitis. Conclusion: The activity of H. suaveolens is comparable
      to standard insulin (P < 0.01). Both the plant materials have some extra
      pancreatic mechanism like glucose uptake by peripheral tissue.

PMID- 29200756
TI  - G2A Attenuates Propionibacterium acnes Induction of Inflammatory Cytokines in
      Human Monocytes.
AB  - Background: Acne vulgaris is a disease of the pilosebaceous unit characterized by
      increased sebum production, hyperkeratinization, and immune responses to
      Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a
      lipid receptor, G2A, regulates immune responses to a commensal bacterium.
      Objective: To elucidate the inflammatory properties of G2A in monocytes in
      response to PA stimulation. Furthermore, our study sought to investigate pathways
      by which lipids modulate immune responses in response to PA. Methods: Our studies
      focused on monocytes collected from human peripheral blood mononuclear cells, the
      monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use
      of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase
      chain reaction, small interfering RNA (siRNA), and microarray analysis of human
      acne lesions in the measurements of inflammatory markers. Results: G2A gene
      expression is higher in acne lesions compared to normal skin and is inducible by
      the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll
      like receptor 2-dependent expression of G2A as well as the production of the G2A
      ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown
      through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1beta
      possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor
      kappa B p65 pathways. Conclusion: G2A may play a role in quelling inflammatory
      cytokine response to PA, revealing G2A as a potential attenuator of inflammatory
      response in a disease associated with a commensal bacterium.

PMID- 29200757
TI  - Randomized Clinical Trial to Evaluate the Efficacy and Safety of Combination
      Therapy with Short-Pulsed 1,064-nm Neodymium-Doped Yttrium Aluminium Garnet Laser
      and Amorolfine Nail Lacquer for Onychomycosis.
AB  - Background: Onychomycosis is one of the most prevalent fungal diseases in the
      general population. However, treatment is of limited effectiveness and must be
      administered for long periods of time. Systemic antifungal agents are associated
      with adverse effects. Objective: We evaluated the clinical efficacy and safety of
      a 1,064-nm neodymium-doped yttrium aluminium garnet (Nd:YAG) laser with
      amorolfine nail lacquer to treat onychomycosis. Methods: The 128 patients were
      randomly divided to 2 groups: 64 in the experimental group were treated with
      1,064-nm Nd:YAG laser therapy and amorolfine nail lacquer; the other 64 were in a
      control group treated with topical amorolfine lacquer monotherapy. The laser
      treatment was 4 sessions at 4-week intervals and amorolfine lacquer was applied
      once a week for 16 weeks. Efficacy was assessed as response rate from
      standardized photographs with ImagePro(r)Plus (Media Cybernetics, Inc., USA)
      analysis, microscopic examination, and subjective evaluation. Results: At 16
      weeks, the experimental group showed a significantly higher cumulative cure rate
      than the control group (71.88% vs. 20.31%, p<0.0001). Clinical therapeutic
      effects were linked to patient satisfaction. The percent of "very satisfied" or
      "satisfied" responses was higher in the test group than the control group (81.25%
      vs. 23.44%). The treatment regimen was well tolerated, with transient discomfort
      observed in the test group. Conclusion: The 1,064-nm Nd:YAG laser with amorolfine
      nail lacquer was effective and safe for treating onychomycosis. This therapy
      should be considered an alternative treatment, especially for patients with
      contraindications to systemic antifungal agents.

PMID- 29200755
TI  - Current and Future Perspectives of Stem Cell Therapy in Dermatology.
AB  - Stem cells are undifferentiated cells capable of generating, sustaining, and
      replacing terminally differentiated cells and tissues. They can be isolated from
      embryonic as well as almost all adult tissues including skin, but are also
      generated through genetic reprogramming of differentiated cells. Preclinical and
      clinical research has recently tremendously improved stem cell therapy, being a
      promising treatment option for various diseases in which current medical
      therapies fail to cure, prevent progression or relieve symptoms. With the main
      goal of regeneration or sustained genetic correction of damaged tissue, advanced
      tissue-engineering techniques are especially applicable for many dermatological
      diseases including wound healing, genodermatoses (like the severe blistering
      disorder epidermolysis bullosa) and chronic (auto-)inflammatory diseases. This
      review summarizes general aspects as well as current and future perspectives of
      stem cell therapy in dermatology.

PMID- 29200758
TI  - Effect of Different Cooking Methods on Histamine Levels in Selected Foods.
AB  - Background: Histamine in food is known to cause food poisoning and allergic
      reactions. We usually ingest histamine in cooked food, but there are few studies
      about the influence of cooking method on the histamine level. Objective: The
      purpose of this study was to determine the influence of cooking methods on the
      concentration of histamine in foods. Methods: The foods chosen were those kinds
      consumed frequently and cooked by grilling, boiling, and frying. The histamine
      level of the food was measured using enzyme-linked immunosorbent assay. Results:
      Grilled seafood had higher histamine levels than raw or boiled seafood. For meat,
      grilling increased the histamine level, whereas boiling decreased it. For eggs,
      there was not much difference in histamine level according to cooking method.
      Fried vegetables had higher histamine levels than raw vegetables. And fermented
      foods didn't show much difference in histamine level after being boiled.
      Conclusion: The histamine level in food has changed according to the cooking
      method used to prepare it. Frying and grilling increased histamine level in
      foods, whereas boiling had little influence or even decreased it. The boiling
      method might be helpful to control the effect of histamine in histamine-sensitive
      or susceptible patients, compared with frying and grilling.

PMID- 29200759
TI  - Increased Skin Irritation by Hydroquinone and Rsetinoic Acid Used in Combination.
AB  - Background: Hydroquinone (HQ) is frequently combined with retinoic acid (RA) to
      enhance lightening efficacy, which may also affect skin irritancy. Although skin
      irritation leads to postinflammatory hyperpigmentation, little research has been
      performed to compare skin irritancy between each component and the combination.
      Objective: This study was done to examine whether HQ-RA combination increased
      skin irritation induced by HQ or RA alone. Methods: Patch testing was performed
      using maximum therapeutic and higher concentrations of HQ and RA in 10
      volunteers, and then, it was performed using their popular therapeutic
      concentrations and combination in the other 20 volunteers. In vitro irritation
      was also assessed in primary cultured normal human keratinocytes treated with 80%
      and 50% cell survival doses of HQ, 80% cell survival dose of RA, and their
      combination. Results: The combination in patch testing induced stronger erythema
      than the corresponding concentrations of HQ and RA, which was remarkable with use
      of combination of higher concentrations. In cultured keratinocytes, the RA
      combination significantly decreased cell viability, but increased cytotoxicity
      and extracellular interleukin 1 alpha release with corresponding doses of HQ.
      Conclusion: The results of patch tests and in vitro irritation assessment tests
      suggested that HQ and RA increased skin irritation when used in combination.

PMID- 29200760
TI  - Therapeutic Effect of Superficial Cryotherapy on Alopecia Areata: A Prospective,
      Split-scalp Study in Patients with Multiple Alopecia Patches.
AB  - Background: Alopecia areata (AA) affects anagen hair follicles resulting in non
      scarring hair loss. Since its introduction, superficial cryotherapy has been used
      as one of the meaningful treatment modalities for AA. Objective: The purpose of
      this study is to clarify the therapeutic efficacy and safety of superficial
      cryotherapy for treatment of AA. Methods: In 19 patients with multiple bilateral
      AA patches on their scalp, superficial cryotherapy was performed on the right
      side, every 2 weeks. Prednicarbate 0.25% solution was applied twice a day to both
      the treated and the control sides. Clinical improvement was estimated using the
      Severity of Alopecia Tool (SALT) score by 3 different dermatologists, along with
      the changes in terminal and vellus hair count and hair thickness analyzed by
      phototrichogram. Results: After 4 months of treatment, mean terminal hair count
      on the right scalp was 1.6-fold increased (p=0.005), while mean terminal hair
      count on the left scalp showed no significant change (110.1% increase, p=0.285).
      Mean SALT score decrease on the right was 4-fold greater than that on the left
      (40.7% and 9.6%), without statistical significance (p=0.282). Mean vellus hair
      count and mean hair thickness did not show significant changes after superficial
      cryotherapy. No remarkable adverse event was observed. Conclusion: Superficial
      cryotherapy is an efficacious treatment modality with advantages of simplicity
      and noninvasiveness. It can be considered as a meaningful therapeutic modality
      for AA, especially when the disease status is limited to minimal to mild, or the
      conventional AA treatment is not applicable.

PMID- 29200761
TI  - Treatment of Palmar Hyperhidrosis with Tap Water Iontophoresis: A Randomized,
      Sham-Controlled, Single-Blind, and Parallel-Designed Clinical Trial.
AB  - Background: Palmar hyperhidrosis is a common disorder of excessive sweating. A
      number of studies have demonstrated the effectiveness of iontophoresis in the
      treatment of palmar hyperhidrosis. However, controlled clinical studies on
      iontophoresis for palmar hyperhidrosis have been limited. Objective: To determine
      the efficacy and safety of iontophoresis in the treatment of palmar hyperhidrosis
      with a randomized, sham-controlled, single-blind, and parallel-designed study.
      Methods: Twenty nine patients with significant palmar hyperhidrosis were enrolled
      in this study. They received active iontophoresis treatment (group A) or sham
      treatment (group B). Iontophoresis was performed 20 minutes each time, five times
      per week, for 2 weeks. Its efficacy was assessed with starch-iodine test, mean
      sweat secretion rate, and hyperhidrosis disease severity scale. Results: Twenty
      seven of the 29 patients completed the 2-week treatment. After completion of 10
      times of treatment, results of the starch-iodine test showed clinical improvement
      in 92.9% of patients in group A and 38.5% of patients in group B (p=0.001). The
      mean sweat secretion rate was reduced by 91.8% of patients in group A and by
      39.1% of patients in group B (p<0.001). Improvement in quality of life was
      reported by 78.6% of patients in group A and by 30.8% of patients in group B
      (p=0.028). In group A, one case of localized adverse event was noted, although no
      adverse event was encountered in group B. Conclusion: Tap water iontophoresis
      could be used as an effective and safe treatment modality for palmar
      hyperhidrosis.

PMID- 29200762
TI  - Allergen Sensitization Pattern by Sex: A Cluster Analysis in Korea.
AB  - Background: Allergens tend to sensitize simultaneously. Etiology of this
      phenomenon has been suggested to be allergen cross-reactivity or concurrent
      exposure. However, little is known about specific allergen sensitization
      patterns. Objective: To investigate the allergen sensitization characteristics
      according to gender. Methods: Multiple allergen simultaneous test (MAST) is
      widely used as a screening tool for detecting allergen sensitization in
      dermatologic clinics. We retrospectively reviewed the medical records of patients
      with MAST results between 2008 and 2014 in our Department of Dermatology. A
      cluster analysis was performed to elucidate the allergen-specific immunoglobulin
      (Ig)E cluster pattern. Results: The results of MAST (39 allergen-specific IgEs)
      from 4,360 cases were analyzed. By cluster analysis, 39items were grouped into 8
      clusters. Each cluster had characteristic features. When compared with female,
      the male group tended to be sensitized more frequently to all tested allergens,
      except for fungus allergens cluster. Conclusion: The cluster and comparative
      analysis results demonstrate that the allergen sensitization is clustered,
      manifesting allergen similarity or co-exposure. Only the fungus cluster allergens
      tend to sensitize female group more frequently than male group.

PMID- 29200763
TI  - The Lateral Tarsal Strip for Paralytic Ectropion in Patients with Leprosy.
AB  - Background: In patients with leprosy, paralysis of the facial nerve results in
      the lower eyelid ectropion and lagophthalmos as a sequela even when the leprosy
      is cured. Paralytic ectropion causes many functional and cosmetic eye problems,
      leading to blindness if left untreated. Objective: The purpose of this
      retrospective study is to evaluate the efficacy of surgical correction of
      paralytic ectropion, the lateral tarsal strip, in patients with leprosy. Methods:
      Between 2010 and 2015, 40 Korean patients (44 eyelids) with paralytic ectropion
      who had visited Korean Hansen Welfare Association Hospital were treated with the
      lateral tarsal strip. Four-point patients' global assessment scale, local
      complications, and recurrence were assessed at the end of follow-up period. The
      average follow-up period was 12 months. Results: In the 44 eyelids, recurrence
      was observed in 5 cases (5/44, 11.4%). There were no serious postoperative
      complications except mild size discrepancy of both eyes. Most patients were
      satisfied with the results and mean satisfaction scale was 2.6/3. Conclusion: The
      lateral tarsal strip is a simple, safe, and effective treatment method for the
      dermatologic surgeon to correct paralytic ectropion of mild to moderate degree in
      patients with leprosy.

PMID- 29200764
TI  - Various Wavelengths of Light-Emitting Diode Light Regulate the Proliferation of
      Human Dermal Papilla Cells and Hair Follicles via Wnt/beta-Catenin and the
      Extracellular Signal-Regulated Kinase Pathways.
AB  - Background: The human dermal papilla cells (hDPCs) play an important role in
      regulation of hair cycling and growth. Objective: The aim of this study was to
      investigate the effect of different wavelengths of light-emitting diode (LED)
      irradiation on the proliferation of cultured hDPCs and on the growth of human
      hair follicles (HFs) in vitro. Methods: We examined the effect of LED irradiation
      on Wnt/beta-catenin signaling and mitogen-activated protein kinase (MAPK)
      pathways in hDPCs. Anagen HFs were cultured with LED irradiation and elongation
      of each hair shaft was measured. Results: The most potent wavelength in promoting
      the hDPC proliferation is 660 nm and 830 nm promoted hDPC proliferation to a
      lesser extent than 660 nm. Various wavelengths significantly increased beta
      catenin, Axin2, Wnt3a, Wnt5a and Wnt10b mRNA expression. LED irradiation
      significantly increased beta-catenin and cyclin D expression, and the
      phosphorylation of MAPK and extracellular signal-regulated kinase (ERK). HFs
      irradiated with 415 nm and 660 nm grew longer than control. Conclusion: Our
      result suggests that LED has a potential to stimulate hDPC proliferation via the
      activation of Wnt/beta-catenin signaling and ERK pathway. To our best knowledge,
      this is the first report which investigated that the effect of various
      wavelengths of LED on hDPC proliferation and the underlying mechanisms.

PMID- 29200765
TI  - Simvastatin/Ezetimibe Therapy for Recalcitrant Alopecia Areata: An Open
      Prospective Study of 14 Patients.
AB  - Background: Simvastatin belongs to the statin family, whose members have
      immunomodulatory activities. Ezetimibe have synergetic effects when co
      administered with simvastatin. In several case reports, alopecia totalis and
      alopecia universalis were successfully treated with simvastatin/ezetimibe,
      suggesting that this combination could be a new efficient therapy for
      recalcitrant alopecia areata (AA). Objective: To verify the efficacy of the
      simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the
      relationship between various treatment responses and prognostic factors. Methods:
      This prospective open study was performed in patients with recalcitrant AA with
      the bald surface exceeding 75%. All patients took simvastatin (40 mg) and
      ezetimibe (10 mg) daily. The extent of hair regrowth expressed as percentage of
      the bald area was used to evaluate the effectiveness of the therapy. Results: Of
      14 enrolled patients, 4 patients (28.6%) were judged as responders showing
      regrowth of 30% to 80% after 3 months of treatment. The mean age of onset in non
      responders was significantly lower than in responders. The total score of
      prognostic factors, calculated as a sum of factors related to poor prognosis, was
      much lower in responders than in non-responders. Conclusion: The remission rate
      in this study was unsatisfactory. However, since the recruited patients had not
      responded to any other treatments for AA, simvastatin/ezetimibe can still be
      considered as an alternative treatment for recalcitrant AA. The total scores of
      the prognostic factors were statistically different between responders and non
      responders. These results can be used to predict the outcome of treatment with
      simvastatin/ezetimibe and anticipate prognosis.

PMID- 29200767
TI  - Serologic Response to Treatment in Human Immunodeficiency Virus-Negative Syphilis
      Patients Using Automated Serological Tests: Proposals for New Guidelines.
AB  - Background: Automated analyzer-based nontreponemal serological tests for syphilis
      (STS) have been used for several decades. Objective: In this study, we evaluated
      serological responses to treatment and proposed clinical guidelines for automated
      STS. Methods: This retrospective cohort study analyzed human immunodeficiency
      virus-negative syphilis patients who were diagnosed with automated rapid plasma
      reagin (auto RPR) tests as a nontreponemal STS, and who also received the
      fluorescent treponemal antibody-absorption test as a confirmatory test. The ratio
      of auto RPR values after treatment against those at baseline was defined as the
      auto RPR ratio for the analysis of the serological response to treatment. The
      cutoff value for reliable seroreversion prediction was assessed with receiver
      operating-characteristic curves. Results: Overall, 89.7% of participants (78/87)
      seroreverted and 10.3% of participants (9/87) remained serofast during the two
      year follow-up period. We were unable to describe trends in the changes among
      auto RPR values within six months after treatment because of high variation. All
      of the patients who had an auto RPR ratio >=1.0 after six months continuously had
      positive serologic results during their 24-month follow-up and were classified as
      a serofast group. The receiver-operating-characteristic curves revealed a 25%
      reduction in auto RPR values nine months after treatment and predicted
      seroreversion with a sensitivity of 96.2% and a specificity of 100%. Conclusion:
      The most important primary checkpoint for syphilis treatment response is an
      increase in automated nontreponemal STS six months after treatment. Thus, we
      recommend monitoring the treatment response with an auto RPR.

PMID- 29200766
TI  - Prevalence of Psoriasis in Korea: A Population-Based Epidemiological Study Using
      the Korean National Health Insurance Database.
AB  - Background: Although psoriasis is universal in its occurrence worldwide, its
      prevalence varies by geographic location and race. A few hospital-based surveys
      have reported on the demographic characteristics in Korean patients with
      psoriasis. However, a nation-wide study on the prevalence of psoriasis in Korea
      remains uncompleted. Objective: The purpose of this study was to determine the
      prevalence of psoriasis in Korea and to describe the demographic and social
      characteristics of afflicted individuals. Methods: We identified patients with
      psoriasis using a relevant diagnostic code from the sixth revision of the Korean
      Standard Classification of Disease in the 2011~2015 claims database of the Health
      Insurance Review and Assessment Service of Korea. We estimated the annual
      prevalence of psoriasis and described the age and sex distribution of the
      patients, type and severity of psoriasis, comorbidities, type of health
      insurance, type of health-care institution and residence area. Patients with
      moderate-to-severe psoriasis were defined as those who had been treated with
      phototherapy, classical systemic agents, and/or biologic agents. Results: The
      standardized prevalence of psoriasis was 453 per 100,000 individuals of the
      database population in 2015. We found male preponderance with a 1.3:1 male-to
      female ratio, and that the largest number of patients belonged to the age group
      of 50s. Of the patients diagnosed with psoriasis in 2015, 83.8% had plaque
      psoriasis and 22.6% had moderate-to-severe psoriasis. Conclusion: The annual
      standardized prevalence of psoriasis in Korea was 453 per 100,000 of the
      population in 2015.

PMID- 29200768
TI  - Congenital Non-Neural Granular Cell Tumor Mimicking Nevus Lipomatosus
      Superficialis.
AB  - A 4-month-old infant presented with asymptomatic soft nodules on his right
      forearm, which had developed since birth. On the suspicion of nevus lipomatosus
      superficialis (NLS), biopsy was performed. Histopathologic findings showed
      monomorphic polygonal cells with abundant granular cytoplasm. Immunohistochemical
      stains for CD68 and vimentin were strongly positive, but were negative for S-100
      protein. Based on the pathologic findings, the patient was diagnosed as non
      neural granular cell tumor (NN-GCT). GCT can be divided into conventional and non
      neural GCT by immunoreactivity for S-100 protein. NN-GCT is typically manifested
      as a well-circumscribed, papulo-nodular dermal mass, and is known to occur in a
      younger group than does in conventional GCT, but is rare among children. To our
      knowledge, there have been no case reports of NN-GCT which appeared at birth and
      presented as grouped nodules. Therefore, we report this interesting case of
      congenital NN-GCT clinically mimicking NLS.

PMID- 29200769
TI  - Treatment of Melasma and Post-Inflammatory Hyperpigmentation by a Picosecond 755
      nm Alexandrite Laser in Asian Patients.
AB  - The picosecond lasers have shown to effectively treat tattoo pigments that are
      intractable to previous multiple Q-switched (QS) laser treatments. Therefore we
      hypothesized that a picosecond laser would show better efficacy with minimal
      adverse events in the treatment of melasma and post-inflammatory
      hyperpigmentation (PIH) that are difficult to treat with conventional QS lasers.
      Two patients with melasma and one patient with PIH were treated with a Picosecond
      755-nm Alexandrite Laser (Cyanosure, USA). All patients were Korean with skin
      type IV and no longer responding to QS laser treatments. Laser treatment was well
      tolerated in all the patients. Adverse events such as PIH were not reported
      during 8 weeks of follow up period. After the multiple treatment sessions, one
      patient reported fair improvement and two patients reported good improvement.
      Consistent with the clinical results, ex vivo skin model irradiated with a
      Picosecond 755-nm Alexandrite Laser also showed decreased epidermal keratinocyte
      necrosis compared with the 532-nm QS Neodymium-Doped Yttrium Aluminium Garnet
      Laser (Lutronic, Korea) yet decreased melanin content. In conclusion, the
      Picosecond 755-nm Alexandrite Laser may be useful for effective treatment of
      intractable melasma and PIH with fewer adverse events in dark Asian skin.

PMID- 29200770
TI  - Psoriasis, Vitiligo and Crohn's Disease Co-Existing in a Single Patient: A
      Variant Type of Multiple Autoimmune Syndrome?
AB  - Multiple autoimmune syndrome (MAS) is a rare condition, in which at least three
      well-defined autoimmune diseases co-occur in a single patient. Although the
      pathogenesis of MAS remains poorly understood, genetic, immunological, hormonal,
      and environmental factors may all play a role. Although three classic subtypes of
      MAS are well known, several cases that could not be placed into any of these
      three categories have recently been reported. To the best of our knowledge, the
      co-existence of psoriasis, vitiligo, and Crohn's disease has been reported in
      only one patient, who had a total of five autoimmune diseases (alopecia areata
      and oral lichen planus in addition to the three conditions mentioned). We herein
      describe a rare case of MAS presenting with psoriasis, vitiligo, and Crohn's
      disease, and suggest that tumor necrosis factor-alpha may be associated with the
      pathogenesis of all three conditions.

PMID- 29200771
TI  - Syringoid Eccrine Carcinoma of the Thigh.
AB  - Syringoid eccrine carcinoma (SEC) is a rare cutaneous malignant tumor thought to
      be derived from eccrine sweat apparatus. It is usually present in the head, neck
      and trunk region, and often occurs in the fourth to seventh decades of life. A 94
      year-old male patient visited our department with an 80-year history of a lesion
      showing a 2*2 cm sized well-demarcated round shaped erythematous to pinkish
      colored nodule with ulcer on his left thigh. Histological findings revealed a
      tumor consisted mainly of numerous small cords and nests forming luminal or
      tubular structures and tumor cells showing variable atypia. Some ductal
      structures showed tadpole appearance. On immunohistochemical staining, epithelial
      membrane antigen, S-100, cytokeratin 7 and carcinoembryonic antigen were reactive
      and Ki-67 showed less than 10% positivity. Based on these findings, the final
      diagnosis was made as SEC. The patient was treated with local wide excision and
      didn't show any recurrence during the follow-up period of 12 months. Herein, we
      report a very rare case of SEC which occurred on the left thigh and discuss 10
      cases of SEC presented on the extremities, including our case.

PMID- 29200772
TI  - Sclerema Neonatorum in a Full-Term Infant Showing Favorable Prognosis.
AB  - Sclerema neonatorum (SN) is a rare disease characterized by firm, indurated, waxy
      skin lesions extending throughout the body, sparing the fat-free soles, palms,
      and genitalia. The prognosis of SN is generally very poor, with a high fatality
      rate. We report the case of a full-term infant with delayed onset of SN showing
      good prognosis. A 4-month-old Korean male infant presented with diffuse waxy,
      sclerotic skin lesions on the whole body, sparing the face, nipples, and genital
      area, which began developing at 2 months of age. Histopathologic findings of the
      sclerotic skin lesions showed wide, fibrous intersecting bands in the
      subcutaneous fat tissue. Only sparse infiltration of lymphocytes and histiocytes
      was observed in the fat lobules and septa. Based on clinical presentation and
      histopathologic findings, he was diagnosed with SN. The patient survived with
      conservative care and had mild improvement of the skin lesions on his follow-up
      visit at 12 months of age.

PMID- 29200773
TI  - Paradoxical Flare of Psoriasis after Ustekinumab Therapy.

PMID- 29200774
TI  - Therapeutic Effects of a Light Emitting Diode at a Variety of Wavelengths on
      Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

PMID- 29200775
TI  - Seven Cases of Senile Gluteal Dermatoses Developed with Ulcer.

PMID- 29200776
TI  - Novel KIT Missense Mutation P665S in a Chinese Piebaldism Family.

PMID- 29200777
TI  - Palisaded Neutrophilic Granulomatous Dermatitis in a Patient with Systemic
      Sclerosis-Rheumatoid Arthritis Overlap Syndrome.

PMID- 29200778
TI  - A Case of Segmental (Zosteriform) Juvenile Xanthogranuloma.

PMID- 29200779
TI  - Primary Angiosarcoma of the Skin Presenting as Mild Erythema.

PMID- 29200780
TI  - Large Edematous Purpuric Plaques after Lipolysis Acupuncture.

PMID- 29200781
TI  - Eosinophilic Annular Erythema Associated with Churg-Strauss Syndrome.

PMID- 29200782
TI  - Analysis of Personality Trait in Patients with Alopecia Areata.

PMID- 29200783
TI  - Which Skin Type Is Prevalent in Korean Post-Adolescent Acne Patients?: A Pilot
      Study Using the Baumann Skin Type Indicator.

PMID- 29200784
TI  - Inverse Psoriasis with Autoimmune Hepatitis.

PMID- 29200785
TI  - Association of Hepatitis B Virus Infection and Psoriasis.

PMID- 29200786
TI  - Tattoo Granuloma Restricted to Red Dyes.

PMID- 29200787
TI  - A Type II Segmental Vitiligo Developed under Infliximab Treatment for Ulcerative
      Colitis.

PMID- 29200788
TI  - Corrigendum: The Effect of Micro-Spicule Containing Epidermal Growth Factor on
      Periocular Wrinkles.
AB  - [This corrects the article on p. 187 in vol. 29, PMID: 28392646.].

PMID- 29200790
TI  - A weighted denoising method based on Bregman iterative regularization and
      gradient projection algorithms.
AB  - A weighted Bregman-Gradient Projection denoising method, based on the Bregman
      iterative regularization (BIR) method and Chambolle's Gradient Projection method
      (or dual denoising method) is established. Some applications to image denoising
      on a 1-dimensional curve, 2-dimensional gray image and 3-dimensional color image
      are presented. Compared with the main results of the literatures, the present
      numerical results of the proposed method are improved.

PMID- 29200789
TI  - Pharmacovigilance: A public health priority for South Africa.
AB  - South Africa has been engaged in pharmacovigilance (PV) activities to assess the
      impact of adverse drug reactions on public safety and health for 40 years.
      Activities have evolved from passive regulatory reporting to encompass active
      surveillance systems. The HIV and AIDS and TB epidemics stimulated
      pharmacoepidemiological research into the risks associated with medicines used in
      the standardised regimens of mass treatment programmes. Specific safety concerns,
      supported by robust local cohort data, have prompted major changes to national
      and international treatment policies. This chapter describes the expanding body
      of local knowledge and the historical and emergent surveillance systems that
      address the burden of drug-related harms, noting the challenges to health system
      responsiveness. The South African context presents a unique opportunity to
      characterise the scale and nature of such harms in mass HIV and AIDS and TB
      treatment programmes. The use of complex regimens at scale poses new PV
      challenges. There is an urgent need to develop cohesive, sustainable systems to
      support evidence-based decisions on appropriate regimen choices, while minimising
      medicine-associated risks. The increasing use of computerised clinical,
      laboratory and dispensing records, with unique patient identifiers facilitating
      data linkage, will increase PV surveillance capacity. A coherent national PV
      framework is an essential part of medicines policy, encompassing regulatory,
      programmatic and individual needs. Key pillars of this framework include: (i)
      consolidation and expansion of active and passive PV surveillance, optimising
      existing programmes; (ii) prioritising post-marketing monitoring within the new
      health products regulatory authority; and (iii) instilling a culture of active
      risk management in clinical practice through the creation of effective channels
      of communication and feedback into policy and practice.

PMID- 29200791
TI  - Updating QR factorization procedure for solution of linear least squares problem
      with equality constraints.
AB  - In this article, we present a QR updating procedure as a solution approach for
      linear least squares problem with equality constraints. We reduce the constrained
      problem to unconstrained linear least squares and partition it into a small
      subproblem. The QR factorization of the subproblem is calculated and then we
      apply updating techniques to its upper triangular factor R to obtain its
      solution. We carry out the error analysis of the proposed algorithm to show that
      it is backward stable. We also illustrate the implementation and accuracy of the
      proposed algorithm by providing some numerical experiments with particular
      emphasis on dense problems.

PMID- 29200793
TI  - Some refinements of operator reverse AM-GM mean inequalities.
AB  - In this paper, we prove the operator inequalities as follows: Let [Formula: see
      text] be positive operators on a Hilbert space with [Formula: see text] and
      [Formula: see text]. Then for every positive unital linear map Phi, [Formula: see
      text] and [Formula: see text] Moreover, we prove Lin's conjecture when [Formula:
      see text].

PMID- 29200792
TI  - On strong KKT type sufficient optimality conditions for multiobjective semi
      infinite programming problems with vanishing constraints.
AB  - In this paper, we consider a nonsmooth multiobjective semi-infinite programming
      problem with vanishing constraints (MOSIPVC). We introduce stationary conditions
      for the MOSIPVCs and establish the strong Karush-Kuhn-Tucker type sufficient
      optimality conditions for the MOSIPVC under generalized convexity assumptions.

PMID- 29200794
TI  - An equivalent condition to the Jensen inequality for the generalized Sugeno
      integral.
AB  - For the classical Jensen inequality of convex functions, i.e., [Formula: see
      text] an equivalent condition is proved in the framework of the generalized
      Sugeno integral. Also, the necessary and sufficient conditions for the validity
      of the discrete form of the Jensen inequality for the generalized Sugeno integral
      are given.

PMID- 29200795
TI  - Bergman projections on weighted Fock spaces in several complex variables.
AB  - Let phi be a real-valued plurisubharmonic function on [Formula: see text] whose
      complex Hessian has uniformly comparable eigenvalues, and let [Formula: see text]
      be the Fock space induced by phi. In this paper, we conclude that the Bergman
      projection is bounded from the pth Lebesgue space [Formula: see text] to
      [Formula: see text] for [Formula: see text]. As a remark, we claim that Bergman
      projections are also well defined and bounded on Fock spaces [Formula: see text]
      with [Formula: see text]. We also obtain the estimates for the distance induced
      by phi and the [Formula: see text]-norm of Bergman kernel for [Formula: see
      text].

PMID- 29200796
TI  - Explicit bounds of unknown function of some new weakly singular retarded integral
      inequalities for discontinuous functions and their applications.
AB  - The purpose of the present paper is to establish some new retarded weakly
      singular integral inequalities of Gronwall-Bellman type for discontinuous
      functions, which generalize some known weakly singular and impulsive integral
      inequalities. The inequalities given here can be used in the analysis of the
      qualitative properties of certain classes of singular differential equations and
      singular impulsive equations.

PMID- 29200797
TI  - Lower bounds for the low-rank matrix approximation.
AB  - Low-rank matrix recovery is an active topic drawing the attention of many
      researchers. It addresses the problem of approximating the observed data matrix
      by an unknown low-rank matrix. Suppose that A is a low-rank matrix approximation
      of D, where D and A are [Formula: see text] matrices. Based on a useful
      decomposition of [Formula: see text], for the unitarily invariant norm [Formula:
      see text], when [Formula: see text] and [Formula: see text], two sharp lower
      bounds of [Formula: see text] are derived respectively. The presented simulations
      and applications demonstrate our results when the approximation matrix A is low
      rank and the perturbation matrix is sparse.

PMID- 29200798
TI  - Mitigating Water Absorption in Waveguides Made From Unannealed PECVD SiO2.
AB  - Water absorption was studied in two types of waveguides made from unannealed
      plasma enhanced chemical vapor deposition (PECVD) SiO2. Standard rib anti
      resonant reflecting optical waveguides (ARROWs) were fabricated with thin films
      of different intrinsic stress and indices of refraction. Buried ARROWs (bARROWs)
      with low and high refractive index differences between the core and cladding
      regions were also fabricated from the same types of PECVD films. All waveguides
      were subjected to a heated, high humidity environment and their optical
      throughput was tested over time. Due to water absorption in the SiO2 films, the
      optical throughput of all of the ARROWs decreased with time spent in the wet
      environment. The ARROWs with the lowest stress SiO2 had the slowest rate of
      throughput change. High index difference bARROWs showed no decrease in optical
      throughput after 40 days in the wet environment and are presented as a solution
      for environmentally stable waveguides made from unannealed PECVD SiO2.

PMID- 29200800
TI  - The Acceptance of Cosmetic Surgery Scale: Confirmatory Factor Analyses and
      Validation among Serbian Adults.
AB  - We examined the validity of the Serbian version of the Acceptance of Cosmetic
      Surgery Scale (ACSS; Henderson-King and Henderson-King 2005). A total of 622
      Serbian adults completed the ACSS, along with Serbian translations of measures
      for the discrepancy between actual body weight and ideal body weight, body
      appreciation, sociocultural attitudes toward appearance, and demographics.
      Confirmatory factor analyses were conducted to compare how different ACSS models
      fitted the collected data. A three-factor model provided the best fit to the data
      relative to two- and one-factor models. The three-factor model had good internal
      consistency, convergent and discriminant validity, and nomological validity. The
      ACSS seems to be a valid instrument for use in Serbian populations. Our study
      will contribute towards better understanding of the acceptance of cosmetic
      surgery from a cross-cultural perspective.

PMID- 29200799
TI  - Improving police interventions during mental health-related encounters: Past,
      present and future.
AB  - There are calls across America for police to re-imagine themselves as "guardians"
      rather than "warriors" in the performance of their innumerable duties. The
      contentious history of police attitudes and practices surrounding encounters with
      people affected by mental illnesses can be understood through the lens of this
      wider push toward guardianship. At least as far back as the de
      institutionalization of mental health care and the profound lack of community
      based resources to fill service deficits, the role of police as mental health
      interventionists has been controversial and complex. This paper reviews the first
      wave of reform efforts designed to re-shape police sensibilities and practices in
      the handling of mental health-related encounters. We argue that such efforts,
      centred on specialized training and cooperative agreements with the health care
      sector, have advanced a guardian mindset through improved knowledge and attitudes
      about mental health vulnerabilities and needs. Building on the progress made, we
      suggest there are critical opportunities for a new wave of efforts that can
      further advance the guardianship agenda. We highlight three such opportunities:
      (1) Enhancing experiences of procedural justice during mental health-related
      encounters; (2) Building the evidence base through integrated data sets; and (3)
      Balancing a "case-based" focus with a "place-based" focus.

PMID- 29200801
TI  - Social Functioning and Coping Strategies in Romanian and Moldavian Adolescents
      with Chronic Diseases.
AB  - The present study aimed to explore the cultural differences in social functioning
      and coping strategies in chronically ill adolescents. One hundred sixty-eight
      chronically ill adolescents (45.8 % girls), age 11 to 17 years from Romania (N =
      78) and Republic of Moldova (N = 90) were recruited. Participants filled in self
      assessment measures for social functioning problems and coping strategies.
      Results indicated cross-cultural differences in the studied factors: Moldavian
      adolescents reported more social functioning problems and higher use of
      maladaptive coping strategies, while using less adaptive strategies than Romanian
      counterparts. The associations between social functioning and maladaptive coping
      strategies were stronger for Romanian than Moldavian adolescents. Further,
      various coping strategies acted as important predictors for social functioning in
      the two country samples. Findings suggest that, while the direction of the
      relation between coping and social functioning in chronically ill adolescents is
      cultural invariant, the importance played by specific coping strategies in
      determining social functioning varies by cultural context. Therefore, clinical
      interventions aimed at improving the social functioning of chronically ill
      adolescents should take into account the reality of their cultural setting.

PMID- 29200802
TI  - Voluntary and Involuntary Singlehood and Young Adults' Mental Health: an
      Investigation of Mediating Role of Romantic Loneliness.
AB  - The present study tested the hypothesis that single young adults who perceive
      their singlehood as voluntary would report a higher level of positive mental
      health (i.e., emotional, psychological and social well-being), lower levels of
      mental health illness (i.e., somatic symptoms, anxiety, social dysfunction,
      severe depression) and romantic loneliness in comparison to young adults who
      perceive their singlehood as involuntary. This paper also investigated whether
      romantic loneliness mediates the relationship between voluntary and involuntary
      singlehood, positive mental health, and mental health illness. The study sample
      included 151 participants (86 females and 65 males) aged 20-26 (M = 22.48, SD =
      2.01) from Poland. The main findings were that voluntarily single young adults
      reported a lower level of romantic loneliness compared to involuntarily single
      young adults. The two groups differed neither in regard to positive mental health
      nor in regard to mental health problems. In addition, gender differences were
      observed solely in the domain of romantic loneliness, with women reporting
      greater romantic loneliness than men. The mediation analysis revealed that
      romantic loneliness does not mediate the relationship between voluntary and
      involuntary singlehood, positive mental health, and mental health illness.
      Voluntary and involuntary singlehood was predictive of somatic symptoms, anxiety
      and insomnia, severe depression, and romantic loneliness.

PMID- 29200803
TI  - Neighborhood Opportunity and Location Affordability for Low-Income Renter
      Families.

PMID- 29200804
TI  - Naturalness Preserved Image Enhancement Using a priori Multi-Layer Lightness
      Statistics.
AB  - Enhancement of non-uniformly illuminated images often suffers from over
      enhancement and produces unnatural results. This paper presents a naturalness
      preserved enhancement method for non-uniformly illuminated images, using a priori
      multi-layer lightness statistics acquired from high-quality images. Our work
      makes three important contributions: designing a novel multi-layer image
      enhancement model; deriving the multi-layer lightness statistics of high-quality
      outdoor images, which are incorporated into the multi-layer enhancement model;
      and showing that the overall quality rating of enhanced images is consistent with
      a combination of contrast enhancement and naturalness preservation. Two separate
      human observer evaluation studies were conducted on naturalness preservation and
      overall image quality. The results showed the proposed method outperformed four
      compared state-of-the-art enhancement methods.

PMID- 29200805
TI  - Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Platform for Testing For
      Drug Cardiotoxicity.
AB  - Off-target cardiotoxicity has been a significant impediment to the development of
      new drugs. Traditional platforms for screening for cardiotoxicity are both overly
      sensitive and limited in their ability to predict cardiotoxicity that is often
      only uncovered after years of clinical use. A major impediment has been the lack
      of a human cardiomyocyte cell line. The recent discovery that adult somatic human
      cells (white blood cells or skin fibroblasts) can be reprogrammed into
      pluripotent stem cells (hiPSCs) and then differentiated into beating
      cardiomyocytes (hiPSC-CMs) provides an exciting new platform for drug
      cardiotoxicity and efficacy testing. One major advantage of using patient-derived
      hiPSC-CMs for drug testing is their ability to recapitulate population genetic
      variations (single nucleotide polymorphisms) that influence drug toxicity,
      providing a powerful new tool in the field of pharmacogenomics and personalized
      medicine.

PMID- 29200806
TI  - The Availability of Substances in Adolescence: Influences in Emerging Adulthood.
AB  - This study examines how the availability of substances in the home during
      adolescence and its influence on substance use in young adulthood. Data are drawn
      from the National Longitudinal Study of Adolescent Health (ADD Health). The final
      sample consisted of approximately 15,000 cases from waves 1, 3 and 4.
      Multivariate analyses indicate that the availability of substances in the home
      affects young adult substance use and substance use in later young adulthood. We
      also find that the availability of substances in the home during adolescence is
      associated with an earlier age at first substance use. This study offers further
      evidence for understanding how the home environment affects substance use
      behavior among young adults. In this case, exposure to substances in adolescence,
      and their easy availability increases the likelihood of substance use in
      adolescence, and increases use in young adulthood.

PMID- 29200807
TI  - Collaboration of the NIH and PHS Commissioned Corps in the International Ebola
      Clinical Research Response.
AB  - The U.S. response to the Ebola epidemic resulted in many federal agencies
      assessing their ability to respond to global threats and improve the efficiency
      of humanitarian efforts.

PMID- 29200808
TI  - Developing a Psychometric Instrument to Measure Physical Education Teachers' Job
      Demands and Resources.
AB  - Based on the job demands-resources model, the study developed and validated an
      instrument that measures physical education teachers' job demands-resources
      perception. Expert review established content validity with the average item
      rating of 3.6/5.0. Construct validity and reliability were determined with a
      teacher sample (n = 397). Exploratory factor analysis established a five
      dimension construct structure matching the theoretical construct deliberated in
      the literature. The composite reliability scores for the five dimensions range
      from .68 to .83. Validity coefficients (intraclass correlational coefficients)
      are .69 for job resources items and .82 for job demands items. Inter-scale
      correlational coefficients range from -.32 to .47. Confirmatory factor analysis
      confirmed the construct validity with high dimensional factor loadings (ranging
      from .47 to .84 for job resources scale and from .50 to .85 for job demands
      scale) and adequate model fit indexes (root mean square error of approximation =
      .06). The instrument provides a tool to measure physical education teachers'
      perception of their working environment.

PMID- 29200809
TI  - A Gendered Approach to Understanding the Roles of Social Bonding, Personal
      Control, and Strain on College Dating Violence in Emerging Adulthood.
AB  - Borrowing insights from concepts that have been shown to predict deviant or
      criminal outcomes (i.e., social bonding, personal control, and strain), this
      study examined dating violence from the perpetrators' and gender-relevance
      perspective among young college students (18-25 years old). This study raised 2
      research questions: Were social bonding, personal control, and strain associated
      with college dating violence? How did these associations differ by gender? In
      sum, 2 types of social bonding (commitment to goal attainment and spending time
      with delinquent peers) were linked to psychological aggression in dating. Whereas
      self-control was negatively related to dating violence perpetration, antisocial
      tendencies were associated with physical aggression. Further, all the strain
      measures (i.e., daily hassles, relationship distress, and couple conflict) had a
      positive association with dating violence. When gender was considered, self
      control had a protective effect for women and antisocial tendencies served as a
      risk factor for increased psychological violence among men.

PMID- 29200810
TI  - Surface Tension and Adsorption Studies by Drop Profile Analysis Tensiometry.
AB  - Surface tension and dilational viscoelasticity of solutions of various
      surfactants measured with bubble and drop profile analysis tensiometry are
      discussed. The study also includes experiments on the co-adsorption of surfactant
      molecules from a solution drop and alkane molecules from saturated alkane vapor
      phase. Using experimental data for 12 surfactants with different surface
      activities, it is shown that depletion due to adsorption of surfactant from the
      drop bulk can be significant. An algorithm is proposed quantitatively to take
      into consideration the depletion effect which is required for a correct
      description of the co-adsorption of alkanes on the solution drop surface and the
      correct analysis of experimental dynamic surface tension data to determine the
      adsorption mechanism. Bubble and drop profile analysis tensiometry is also the
      method of choice for measuring the dilational viscoelasticity of the adsorbed
      interfacial layer. The same elasticity moduli are obtained with the bubble and
      drop method only when the equilibrium surface pressures are sufficiently small
      (Pi < 15 mN m-1). When the surface pressure for a surfactant solution is larger
      than this value, the viscoelasticity moduli determined from drop profile
      experiments become significantly larger than those obtained from bubble profile
      measurements.

PMID- 29200811
TI  - Alkyl Xylosides: Physico-Chemical Properties and Influence on Environmental
      Bacteria Cells.
AB  - A group of four selected non-ionic surfactants based on carbohydrates, namely
      octyl d-xyloside (C8X), nonyl d-xyloside (C9X), decyl d-xyloside (C10X) and
      dodecyl d-xyloside (C12X), have been investigated to accomplish a better
      understanding of their physico-chemical properties as well as biological
      activities. The surface-active properties, such as critical micelle concentration
      (CMC), emulsion and foam stability, the impact of the compounds on cell surface
      hydrophobicity and cell membrane permeability together with their toxicity on the
      selected bacterial strains have been determined as well. The studied group of
      surfactants showed high surface-active properties allowing a decrease in the
      surface tension to values below 25 mN m-1 for dodecyl d-xyloside at the CMC. The
      investigated compounds did not have any toxic influence on two Pseudomonas
      bacterial strains at concentrations below 25 mg L-1. The studied long-chain alkyl
      xylosides influenced both the cell inner membrane permeability and the cell
      surface hydrophobicity. Furthermore, the alkyl chain length, as well as the
      surfactant concentration, had a significant impact on the modifications of the
      cell surface properties. The tested non-ionic surfactants exhibited strong
      surface-active properties accompanied by the significant influence on growth and
      properties of Pseudomonas bacteria cells.

PMID- 29200812
TI  - Application of Micellar Extraction for Isolation of Famotidine from Aqueous
      Samples Prior to its Chromatographic Determination.
AB  - Micellar extraction was applied to isolate famotidine from aqueous samples. This
      drug is an H2 receptor antagonist used for the treatment of stomach diseases. The
      process was performed with a mixture of anionic sodium dodecylsulfate and
      nonionic Triton X-114 surfactants. The effect of different parameters on the
      efficiency of the micellar extraction such as electrolyte and surfactant
      concentration, pH of sample, temperature, shaking and centrifugation time was
      investigated. The influence of foreign substances on a studied process was
      tested. The elaborated procedure was applied for HPLC-UV determination of
      famotidine in natural water samples. The calibration graph was recorded in the
      range 1.35-37.12 MUg mL-1 of the studied compound. The repeatability of the
      method was equal to 7.4%. The limit of detection and quantification values for
      the determination of famotidine by using the proposed method amounted to 0.40 and
      1.25 MUg mL-1, respectively.

PMID- 29200813
TI  - Determination of Dodecanol and Short-Chained Ethoxylated Dodecanols by LC-MS/MS
      (with Electrospray Ionization) After Their Derivatization (with Phenyl
      Isocyanate).
AB  - Abstract: This report describes the application of LC-MS/MS for the separation of
      dodecanol (C12OH) and homogenous fatty alcohols ethoxylated (AE) containing a
      dodecyl moiety and 1-9 ethoxy groups. These ethoxylates and free alcohol were
      derivatized for LC-MS/MS analysis with phenyl isocyanate (PIC). The derivatives
      of analytes with PIC were separated using a C18 column. Gradient elution with a
      mixture of ethyl acetate and acetonitrile (5 mM) was employed. The described
      determination method is characterized by low detection limits (range from 0.005
      ug L-1 for: C12OH, C12EO2-7 to 1 ug L-1 for C12EO1) and quantification limits
      (range from 0.01 ug L-1 for: C12EO5-7 to 2 ug L-1 for C12EO1). The developed and
      validated method was used in combination with liquid-liquid extraction (using
      ethyl acetate) in order to identify and quantitatively determine the C12OH and
      C12EO1-9 present in environmental samples collected from Warta river water in
      Poznan. Graphical abstract: 

PMID- 29200814
TI  - Selective Synthesis of Polyoxyethylene-Polyoxypropylene Block Copolymer
      (Poloxamer) Fatty Acid Monoesters Over Homogeneous Organotin Catalyst.
AB  - The synthesis of selected polyoxyethylene-polyoxypropylene block copolymer
      (poloxamer) fatty acid monoesters is presented. Organotin homogeneous catalyst Sn
      bis(2-ethylhexanoate) effectively catalyzed the esterification reaction of (EO)
      (PO)-(EO) block copolymer (poloxamer) with fatty acids. The reaction proceeded in
      high yield and high selectivity to monoesters. Content of diesters in final
      products was below 1 wt%. The new protocol opened up a high yield and high
      selective method for the synthesis of poloxamer fatty acid monoesters. These
      products are potentially interesting for industrial applications, e.g. in
      lubricants, cosmetics and, in particular, as potential emulsifying agents
      compatible with hydrocarbon bases, such as paraffin.

PMID- 29200815
TI  - Design and Test Research on Cutting Blade of Corn Harvester Based on Bionic
      Principle.
AB  - Existing corn harvester cutting blades have problems associated with large
      cutting resistance, high energy consumption, and poor cut quality. Using bionics
      principles, a bionic blade was designed by extracting the cutting tooth profile
      curve of the B. horsfieldi palate. Using a double-blade cutting device testing
      system, a single stalk cutting performance contrast test for corn stalks obtained
      at harvest time was carried out. Results show that bionic blades have superior
      performance, demonstrated by strong cutting ability and good cut quality. Using
      statistical analysis of two groups of cutting test data, the average cutting
      force and cutting energy of bionic blades and ordinary blades were obtained as
      480.24 N and 551.31 N and 3.91 J and 4.38 J, respectively. Average maximum
      cutting force and cutting energy consumption for the bionic blade were reduced by
      12.89% and 10.73%, respectively. Variance analysis showed that both blade types
      had a significant effect on maximum cutting energy and cutting energy required to
      cut a corn stalk. This demonstrates that bionic blades have better cutting force
      and energy consumption reduction performance than ordinary blades.

PMID- 29200816
TI  - Multivariable prediction model for suspected giant cell arteritis: development
      and validation.
AB  - Purpose: To develop and validate a diagnostic prediction model for patients with
      suspected giant cell arteritis (GCA). Methods: A retrospective review of records
      of consecutive adult patients undergoing temporal artery biopsy (TABx) for
      suspected GCA was conducted at seven university centers. The pathologic diagnosis
      was considered the final diagnosis. The predictor variables were age, gender, new
      onset headache, clinical temporal artery abnormality, jaw claudication, ischemic
      vision loss (VL), diplopia, erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), and platelet level. Multiple imputation was performed for missing
      data. Logistic regression was used to compare our models with the non-histologic
      American College of Rheumatology (ACR) GCA classification criteria. Internal
      validation was performed with 10-fold cross validation and bootstrap techniques.
      External validation was performed by geographic site. Results: There were 530
      complete TABx records: 397 were negative and 133 positive for GCA. Age, jaw
      claudication, VL, platelets, and log CRP were statistically significant
      predictors of positive TABx, whereas ESR, gender, headache, and temporal artery
      abnormality were not. The parsimonious model had a cross-validated bootstrap area
      under the receiver operating characteristic curve (AUROC) of 0.810 (95% CI =0.766
      0.854), geographic external validation AUROC's in the range of 0.75-0.85,
      calibration pH-L of 0.812, sensitivity of 43.6%, and specificity of 95.2%, which
      outperformed the ACR criteria. Conclusion: Our prediction rule with calculator
      and nomogram aids in the triage of patients with suspected GCA and may decrease
      the need for TABx in select low-score at-risk subjects. However,
      misclassification remains a concern.

PMID- 29200817
TI  - Evaluation of corneal symmetry after UV corneal crosslinking for keratoconus.
AB  - Purpose: The purpose of this study was to assess UV corneal crosslinking (CXL)
      treatment outcomes for keratoconus by evaluating the corneal regularity in
      patients through follow-up using the Oculus Pentacam. Patients and methods: A
      total of 18 eyes from CXL patients with keratoconus were studied before and after
      CXL treatment, and six eyes from six patients who were not treated with CXL
      served as controls. Treated patients had Pentacam images taken before CXL
      treatment and regularly 3 months post treatment up to the 12th month. Controls
      were imaged during their first appointment and after 12 months. Symmetry and
      asphericity were evaluated and correlated with both best-corrected visual acuity
      (BCVA) and maximum K-readings. Results: In the CXL-treated group, there was a
      significant improvement in the index of symmetrical variation (ISV) and
      keratoconus index (KI) at 3 months and in the index of height asymmetry (IHA) and
      minimum radius of curvature (Rmin) at 9 months post treatment. On the contrary,
      the untreated group's indices showed some significant worsening in ISV, KI,
      central keratoconus index (CKI), and Rmin. A novel finding in our study was a
      slight positive shift of anterior asphericity in the 6 mm, 7 mm, and 8 mm 3
      months after treatment, which had a correlation with BCVA (R2=0.390, p=0.053) and
      a strong correlation with maximum K-reading (R2=0.690, p=0.005). However, the
      untreated group had no significant changes after 1 year. Conclusion: The corneal
      asymmetrical shape is associated with the spherical aberration alteration
      influenced by temporal evolution of surface ablation and increased corneal haze.
      However, insignificant changes in symmetry attest the stabilization effect on
      cornea postoperatively as compared with controls.

PMID- 29200818
TI  - Photodynamic therapy combined with antivascular endothelial growth factor
      treatment for recalcitrant chronic central serous chorioretinopathy.
AB  - Purpose: To determine whether combination photodynamic therapy (PDT) and
      antivascular endothelial growth factor (VEGF) therapy is effective in the
      management of chronic central serous chorioretinopathy (CSC) recalcitrant to
      conventional therapy. Methods: This was a retrospective analysis of eight
      patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory
      drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were
      evaluated with a full ophthalmic examination, spectral-domain optical coherence
      tomography (OCT), fluorescein angiography (FA), and most with indocyanine green
      angiography (ICGA) followed by treatment with half-fluence PDT and intravitreal
      anti-VEGF injection (seven bevacizumab, one aflibercept). Patients were seen in
      follow-up 1 month after treatment. Results: All eight patients achieved complete
      resolution in subretinal fluid following combination treatment. Average duration
      of CSC prior to initiation of combination therapy was 7.5 months. Mean central
      macular thickness on OCT decreased significantly from 401.2+/-52.7 um to 297.9+/
      18.2 um (p=0.0010) by 4 months after treatment (1.63+/-1.18 months). Seven of
      eight patients were followed up for an average of 13 months with no recurrence
      during that time. One case recurred at 8 months and was treated with repeat
      combination at that time. Frank choroidal neovascularization (CNV) was not
      identified in these cases on FA or ICGA studies. Eight of eight patients showed
      significant improvement in vision from a logMAR of 0.1125+/-0.099 to 0.0125+/
      0.064 (p=0.019). Conclusion: Combination PDT and anti-VEGF is effective for
      chronic CSC which has failed conventional therapy. Associated CNV and/or
      inflammation may be reasons for greater success in patients treated with
      combination therapy.

PMID- 29200819
TI  - The efficacy of preoperative posterior subtenon injection of triamcinolone
      acetonide in noninfectious uveitic patients with secondary glaucoma undergoing
      trabeculectomy.
AB  - Objective: The aim of this study was to evaluate the efficacy and safety of
      preoperative posterior subtenon injection of triamcinolone acetonide (PSTA) in
      noninfectious uveitic patients with secondary glaucoma undergoing primary
      trabeculectomy with mitomycin C. Design: This was a retrospective study. Patients
      and methods: We reviewed the medical records of 10 noninfectious uveitic
      patients, who had received a single preoperative PSTA 40 mg/1 mL, with secondary
      glaucoma undergoing primary trabeculectomy with mitomycin C. We collected data
      before and after surgery on intraocular pressure (IOP), anterior chamber (AC)
      cells, best-corrected visual acuity (BCVA), morphologic characteristics of the
      filtering bleb and complications. Results: The mean time between injection and
      surgery was 7.8+/-3.88 days. Postoperative IOP level was significantly lower than
      preoperative level (31.3+/-11.44 mmHg) at all visits (P<0.02). Antiglaucoma
      medications were decreased from preoperative (4.9+/-0.88) to 12-month
      postoperative (0.8+/-1.31; P-value <0.001) and also discontinued in seven eyes
      (70%). About 12 months after surgery, eight eyes (80%) with qualified success and
      two eyes (20%) with failed treatment were recorded. AC cells and BCVA did not
      differ significantly from baseline; however, all inflammations were controlled
      successfully. Most desirable bleb morphology was shown at 12 months as well.
      Complications were blepharoptosis and hypotony maculopathy in two eyes (20%).
      Conclusion: A preoperative PSTA may be an effective and safe option in
      controlling intraocular inflammation and maintaining bleb function after
      trabeculectomy in noninfectious uveitic patients with secondary glaucoma during a
      12-month period.

PMID- 29200820
TI  - The effect of flap thickness on corneal biomechanics after myopic laser in situ
      keratomileusis using the M-2 microkeratome.
AB  - Purpose: The purpose of this study was to determine the effect of flap thickness
      on corneal biomechanics after myopic laser in situ keratomileusis (LASIK).
      Methods: This is a prospective controlled non-randomized, institutional study.
      Patients underwent either epi-LASIK with mitomycin (advanced surface ablation
      [ASA]), thin-flap LASIK (90 um head), or thick-flap LASIK (130 um head). In ASA,
      the Moria Epi-K hydroseparator was used. LASIK flaps were created using the Moria
      M-2 mechanical microkeratome. The corneal hysteresis (CH) and corneal resistance
      factor (CRF) were measured preoperatively and 3 months after surgery, using the
      Ocular Response Analyzer(r). Results: Ten patients (19 eyes) underwent ASA, 11
      patients (16 eyes) underwent thin-flap LASIK, and 11 patients (16 eyes) underwent
      thick-flap LASIK. The mean preoperative CH was 10.47+/-0.88, 10.52+/-1.4, and
      11.28+/-1.4 mmHg (p=0.043), respectively, decreasing after surgery by 1.75+/
      1.02, 1.66+/-1.00, and 2.62+/-1.03 mmHg (p=0.017). The mean reduction of CH per
      micron of central corneal ablation was 0.031, 0.023, and 0.049 mmHg/um (p=0.005).
      Mean preoperative CRF was 10.11+/-1.28, 10.34+/-1.87, and 10.62+/-1.76 mmHg
      (p=0.66), decreasing after surgery by 2.33+/-1.35, 2.77+/-1.03, and 2.92+/-1.10
      mmHg (p=0.308). The mean reduction of CRF per micron of central corneal ablation
      was 0.039, 0.040, and 0.051 mmHg/um (p=0.112). Conclusion: Thick-flap LASIK
      caused a greater reduction of CH and CRF than thin-flap LASIK and ASA, although
      this was statistically significant only for CH. ASA and thin-flap LASIK were
      found to be biomechanically similar.

PMID- 29200821
TI  - Spectropathology-corroborated multimodal quantitative imaging biomarkers for
      neuroretinal degeneration in diabetic retinopathy.
AB  - Introduction: Image-based early detection for diabetic retinopathy (DR) needs
      value addition due to lack of well-defined disease-specific quantitative imaging
      biomarkers (QIBs) for neuroretinal degeneration and spectropathological
      information at the systemic level. Retinal neurodegeneration is an early event in
      the pathogenesis of DR. Therefore, development of an integrated assessment method
      for detecting neuroretinal degeneration using spectropathology and QIBs is
      necessary for the early diagnosis of DR. Methods: The present work explored the
      efficacy of intensity and textural features extracted from optical coherence
      tomography (OCT) images after selecting a specific subset of features for the
      precise classification of retinal layers using variants of support vector machine
      (SVM). Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic
      resonance (NMR) spectroscopy were also performed to confirm the
      spectropathological attributes of serum for further value addition to the OCT,
      fundoscopy, and fluorescein angiography (FA) findings. The serum metabolomic
      findings were also incorporated for characterizing retinal layer thickness
      alterations and vascular asymmetries. Results: Results suggested that OCT
      features could differentiate the retinal lesions indicating retinal
      neurodegeneration with high sensitivity and specificity. OCT, fundoscopy, and FA
      provided geometrical as well as optical features. NMR revealed elevated levels of
      ribitol, glycerophosphocholine, and uridine diphosphate N-acetyl glucosamine,
      while the FTIR of serum samples confirmed the higher expressions of lipids and
      beta-sheet-containing proteins responsible for neoangiogenesis, vascular
      fragility, vascular asymmetry, and subsequent neuroretinal degeneration in DR.
      Conclusion: Our data indicated that disease-specific spectropathological
      alterations could be the major phenomena behind the vascular attenuations
      observed through fundoscopy and FA, as well as the variations in the intensity
      and textural features observed in OCT images. Finally, we propose a model that
      uses spectropathology corroborated with specific QIBs for detecting neuroretinal
      degeneration in early diagnosis of DR.

PMID- 29200822
TI  - Intraocular pressure 1 year after vitrectomy in eyes without a history of
      glaucoma or ocular hypertension.
AB  - Objective: The aim of this study was to investigate the incidence, risk factors,
      and treatment of elevated intraocular pressure (IOP) 1 year after vitrectomy in
      eyes without a history of glaucoma or ocular hypertension. Patients and methods:
      This retrospective study comprised 256 eyes from 256 consecutive patients without
      a history of glaucoma or ocular hypertension who underwent vitrectomy and were
      followed up for 1 year. The incidence of elevated IOP at 1 year after vitrectomy
      was calculated. We compared the characteristics of patients with or without
      elevated IOP to identify possible risk factors for elevated IOP. The treatments
      used to control IOP were recorded and analyzed. Results: A total of 50 patients
      (19.5%) had elevated IOP after vitrectomy at the 1-year follow-up. Tamponade was
      a significant risk factor for elevated IOP (P<0.05). The cumulative rates of
      elevated IOP in eyes with air, balanced salt solution, sulfur hexafluoride,
      perfluoropropane (C3F8), and silicone oil as the tamponade were 0, 10.8%, 5.9%,
      19.8%, and 28.4%, respectively (P<0.05). About 68% of cases of elevated IOP
      occurred within 1 month after vitrectomy. At 1 year after vitrectomy, 29 patients
      (58.0%) had stopped their IOP-lowering drugs and 21 (42.0%) patients were
      continuing these drugs. About 65% of ocular hypertension patients who received
      silicone oil tamponade had not stopped IOP-lowering drugs; this rate was
      significantly greater than that of ocular hypertension patients who received C3F8
      tamponade (18.2%, P<0.05). Conclusion: Elevated IOP is a common complication
      after vitrectomy. Silicone oil tamponade was associated with greater risk of
      elevated IOP and had long-term effects on IOP. Drugs and surgery were used to
      control IOP, and some patients required long-term IOP-lowering therapy.

PMID- 29200823
TI  - Six-month postoperative outcomes of intraoperative OCT-guided surgical cystotomy
      for refractory cystoid macular edema in diabetic eyes.
AB  - Purpose: This study evaluated the outcomes of surgical cystotomy for recurrent
      diabetic cystoid macular edema (CME). Patients and methods: We analyzed 20 eyes
      with a clinical diagnosis of diabetic retinopathy and refractory CME. Release of
      vitreoretinal adhesion, epiretinal membrane (ERM) and internal limiting membrane
      (ILM) peeling and cystotomy guided by intraoperative optical coherence tomography
      (iOCT) were performed in every patient. Pars plana vitrectomy was also performed
      in 17 patients, 11 of whom also underwent lensectomy and intraocular lens
      implantation. Central retinal thickness (CRT), central minimum macular thickness
      (CMMT), macular volume (MV) and best-corrected visual acuity (BCVA) were compared
      preoperatively and 1 and 6 months post surgery. Results: CRT, CMMT and MV
      significantly improved 1 and 6 months post surgery in each group (P<0.01).
      Significant improvements in BCVA were only observed 6 months post surgery
      (P<0.01). No intra- or postoperative complications were observed in all patients.
      Conclusion: CRT, CMMT, MV and BCVA significantly improved 6 months following
      surgical cystectomy. This implies that iOCT-guided cystotomy could be another
      treatment option for refractory CME in diabetic eyes.

PMID- 29200824
TI  - Pharmacodynamic testing and new validated HPLC method to assess the
      interchangeability between multi-source orlistat capsules.
AB  - Background: Orlistat is an irreversible inhibitor of the lipase enzyme that
      prevents trigylcerides from being digested, thereby inhibiting triglyceride
      hydrolysis and absorption. The resultant reduced calorie uptake enables a
      positive effect on weight control. Systemic absorption of the drug is, therefore,
      not necessary for its mode of action. An alternative in vitro study
      (pharmacodynamic) has been introduced for this drug, as in vivo bioavailability
      studies are irrelevant with regard to the achievement of the product's intended
      purposes. Objectives: To develop a new validated high-performance liquid
      chromatography (HPLC) method for the analysis of orlistat and to assess the
      potency and equivalence of three orlistat formulations using the pharmacodynamic
      method as a surrogate indicator of pharmaceutical interchangeability. Methods: A
      new HPLC method was developed for the analysis and for the dissolution studies of
      orlistat in capsules. Pancreatic lipase activity was measured for three different
      capsule products: Orlislim(r), Slimcare(r), and Xenical(r), G1, G2, and the
      brand, respectively. Porcine pancreatic lipase and p-nitrophenyl butyrate (PNPB)
      were placed in a pH 7.4 reaction buffer at 37 degrees C, and substrate hydrolysis
      was monitored by measuring absorbance changes at 410 nm; this was repeated on six
      capsules of each product. The inhibition was expressed by the concentration of
      product, which inhibited 50% of the activity of pancreatic lipase (IC50).
      Results: The new analytical method was suitable for orlistat analysis. Values of
      IC50 from regression lines and equations were 6.14, 8.43, and 7.80 MUg/mL for
      Orlislim(r), Xenical(r), and Slimcare(r), respectively. Conclusion:
      Pharmacodynamic studies of lipase inhibition could be used to support in vitro
      dissolution, which demonstrates interchangeability between generic and branded
      orlistat capsules. Moreover, it could be suggested as an alternative tool to
      bioequivalence studies for orlistat oral products.

PMID- 29200825
TI  - Efficacy and safety of quadruple therapy including tirofiban in the treatment of
      Chinese NSTE-ACS patients failing to receive timely percutaneous coronary
      intervention.
AB  - Background: Although it has been shown to be superior to simple antithrombotic
      drug therapy, most patients are unable to receive timely percutaneous coronary
      intervention (PCI) and are treated with conventional triple antithrombotic
      therapy (aspirin, clopidogrel, low-molecular-weight heparin). Here, we evaluate
      the efficacy and safety of adding low-dose tirofiban to this regimen. Methods: A
      total of 1,783 patient records (unable to receive PCI) indicating non-ST-segment
      elevation acute coronary syndrome (NSTE-ACS) were included. A total of 882
      received conventional triple antithrombotic therapy; 901 received quadruple
      antithrombotic therapy. Efficacy was evaluated in terms of major adverse
      cardiovascular event (MACE) parameters. Safety was evaluated based on the
      occurrence of bleeding events. Data were collected over a 6-month period post
      treatment. Results: The rate of occurrence of MACE was significantly lower in the
      quadruple antithrombotic group (10.5% versus 14.1% at 6 months, P=0.02). The log
      rank test showed improved survival in the quadruple antithrombotic group. Total
      bleeding events were higher in the quadruple antithrombotic group (9.7%) than in
      the triple antithrombotic group (7.1%) (P=0.04); however, this may be attributed
      to increased clinically insignificant minor bleeding events. Conclusion:
      Quadruple antithrombotic therapy demonstrated a superior alternative for the
      treatment of high-risk NSTE-ACS patients failing to receive PCI.

PMID- 29200826
TI  - Anticancer effect of dentatin and dentatin-hydroxypropyl-beta-cyclodextrin
      complex on human colon cancer (HT-29) cell line.
AB  - Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl
      2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena
      excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various
      cancer cells. Because of its hydrophobicity, it is believed that its complexation
      with hydroxy-beta-cyclodextrin (HPbetaCD) will make it a potent inhibitor of
      cancer cell growth. In the current work, the molecular mechanisms of apoptosis
      induced by DEN and DEN-HPbetaCD complex were demonstrated in human colon HT-29
      cancer cells. Materials and methods: After the human colon HT-29 cancer cells
      were treated with DEN and DEN-HPbetaCD complex, their effects on the expression
      of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death
      receptor pathways were detected by Western blot analysis and reverse
      transcription polymerase chain reaction. These markers included caspases-9, 3,
      and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as
      the Bcl-2 family of proteins. Results: At 3, 6, 12, and 24 ug/mL exposure, DEN
      and DEN-HPbetaCD complex significantly affected apoptosis in HT-29 cells through
      the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53,
      p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPbetaCD complex
      also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8,
      and -9. Conclusion: Results of this study indicate that the apoptotic pathway
      caused by DEN and DEN-HPbetaCD complex are mediated by the regulation of caspases
      and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest
      that DEN-HPbetaCD complex may have chemotherapeutic benefits for colon cancer
      patients.

PMID- 29200827
TI  - Severe hypertriglyceridemia and colchicine intoxication following suicide
      attempt.
AB  - Colchicine overdose is uncommon but potentially life threatening. Due to its
      serious adverse systemic effects, overdose must be recognized and treated. We
      report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg) of
      colchicine in a suicide attempt. The patient's clinical manifestations included
      abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and
      rhabdomyolysis. Two unique manifestations of toxicity in this patient were
      profound and persistent, severe hypertriglyceridemia and electrolyte imbalance,
      mainly hypophosphatemia, with no other evident cause except the colchicine
      intoxication. Following intensive supportive treatment, including ventilator
      support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte
      repletion, and zinc supplementation, the patient made a complete recovery.
      Colchicine intoxication is a severe, life-threatening situation that should be
      followed closely in intensive care units. Severe changes in body functions can
      rapidly develop, as previously described in the literature. To our knowledge,
      this extremely elevated triglyceride level has never been reported without the
      administration of propofol, and requires further evaluation.

PMID- 29200828
TI  - Fentanyl-induced respiratory depression is attenuated in pregnant patients.
AB  - Background: Respiratory depression is a complication of intravenous fentanyl
      administration. The effect of pregnancy on respiratory depression following
      opioid administration is unclear. This study investigated the effect of pregnancy
      on fentanyl-induced respiratory depression. Patients and methods: Female patients
      were divided into three groups (n=20 per group): control group (non-pregnant and
      scheduled for laparoscopic surgery), early pregnancy group (pregnant for 45-60
      days and scheduled for abortion), and postpartum group (5-7 days postpartum
      scheduled for complete curettage of uterine cavity). All patients received an
      intravenous infusion of fentanyl 2 MUg/kg. Respiratory rate (RR), end-tidal
      pressure of carbon dioxide (PETCO2), and pulse oxygen saturation (SpO2) were
      recorded continuously from just before fentanyl infusion to 15 min after
      commencing infusion. Plasma levels of progesterone were measured. Results: SpO2
      levels in the early pregnancy and postpartum groups were significantly higher and
      the levels of RR and PETCO2 were significantly lower than the control group. RR
      and SpO2 levels were significantly decreased in all groups, whereas PETCO2 was
      significantly increased after fentanyl infusion. The rates of RR increase and
      SpO2 decrease were significantly faster in the control group than in the other
      groups. The lowest SpO2 after intravenous fentanyl administration was
      significantly positively correlated with plasma progesterone levels. Conclusion:
      Pregnancy improves fentanyl-induced respiratory depression, which may be
      associated with the increased levels of plasma progesterone.

PMID- 29200829
TI  - Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal
      cancer via inhibition of c-MET pathway.
AB  - Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. 5
      Fluorouracil (5-Fu) is the most important chemotherapeutic drug used for the
      treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in
      CRC clinical practice recently. Andrographolide (Andro) is a main bioactive
      constituent of the herb Andrographis paniculata, which has various biological
      effects including anti-inflammation and antitumor activities. In the present
      study, we investigated the effects of combined Andro with 5-Fu against CRC HCT
      116 cells. In vitro studies showed that Andro synergistically enhanced the anti
      proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells.
      Meanwhile, results of the enzyme linked immunosorbent assay indicated that the
      level of phosphorylated cellular-mesenchymal to epithelial transition factor (p
      MET) was decreased by the combination treatment. Further study suggested that
      Andro promoted the antitumor effect of 5-Fu by down-regulating the level of p
      MET. In conclusion, these results confirmed the synergistic antitumor activity of
      Andro on CRC and provide evidence for possible clinical application of Andro for
      enhancing the antitumor effect of 5-Fu in CRC treatment.

PMID- 29200831
TI  - Efficacy and safety of fixed-combination bimatoprost/timolol ophthalmic solution.

PMID- 29200830
TI  - Notoginsenoside R1 attenuates high glucose-induced endothelial damage in rat
      retinal capillary endothelial cells by modulating the intracellular redox state.
AB  - The aim of this study was to examine whether Notoginsenoside R1 (NR1) attenuates
      high glucose-induced cell damage in rat retinal capillary endothelial cells
      (RCECs) and to explore the mechanisms involved. The exposure of rat RCECs to high
      concentration of glucose (30 mM) for 72 h led to significant cytotoxicity,
      including decreased cell viability, reduced mitochondrial DNA copy number,
      increased lactate dehydrogenase release and elevated apoptosis. NR1, when present
      in the culture medium, markedly attenuated the high glucose-induced cytotoxicity
      in rat RCECs. Moreover, high glucose also induced a significant increase in
      intracellular reactive oxygen species and subsequently increased the activity of
      NADPH oxidase and poly-ADP (ribose) polymerase, whereas the activity of catalase
      decreased. The addition of NR1 to the medium significantly reduced the generation
      of reactive oxygen species, inhibited NADPH oxidase and poly-ADP (ribose)
      polymerase activities and increased catalase activity in RCECs, accompanied by a
      reduced cellular nitrotyrosine level. To explore the underlying mechanisms
      involved, the cellular redox status was monitored. Both the cellular NAD+ and
      NADPH levels decreased significantly in high glucose medium, which resulted in a
      marked decrease in the NAD+/NADH and NADPH/NADP+ ratios. High glucose stimulation
      also enhanced the accumulation of GSSG, maintaining the GSH/GSSG ratio lower than
      that in the control group with 5.5 mM glucose. When treated with NR1, the
      cellular NAD+, NADPH and GSH concentrations increased, and the ratios of
      NAD+/NADH, NADPH/NADP+ and GSH/GSSG increased, similar to the control group.
      These results demonstrate that NR1 attenuates high glucose-induced cell damage in
      RCECs. Therefore, NR1 may exert its protective effects via mechanisms that
      involve changes in the cellular redox state.

PMID- 29200832
TI  - Post-discharge evaluation of medication adherence and knowledge of hypertension
      among hypertensive stroke patients in northwestern China.
AB  - Objectives: The aims of this study were to assess the knowledge of hypertension
      (HTN) and investigate risk factors associated with medication adherence among
      hypertensive stroke patients after discharge in northwestern China. Patients and
      methods: A cross-sectional study involving 440 Chinese hypertensive stroke
      patients was conducted in a tertiary hospital in Xi'an, China. Data were
      collected by telephone interviews and patients' medical records. Results: It was
      found that 35.23% of patients were compliant with their antihypertensive drug
      treatments, and 42.95%, 52.27% and 4.77% of patients had poor, moderate and
      adequate knowledge of HTN, respectively. Gender, blood pressure (BP) categories,
      BP monitoring and HTN knowledge were independently associated with
      antihypertensive medication adherence. Conclusion: The medication adherence among
      hypertensive stroke patients in northwestern China was poor. Knowledge of HTN was
      suboptimal. More attention and effective strategies should be designed to the
      factors affecting medication adherence. As knowledge positively affects
      medication adherence, clinical pharmacists should play an important role in
      patients' medication education.

PMID- 29200833
TI  - Positive airway pressure adherence and subthreshold adherence in posttraumatic
      stress disorder patients with comorbid sleep apnea.
AB  - Study objectives: Patients with comorbid posttraumatic stress disorder (PTSD) and
      obstructive sleep apnea (OSA) manifest low adherence to continuous positive
      airway pressure (CPAP) due to fixed, pressure-induced expiratory pressure
      intolerance (EPI), a subjective symptom and objective sign aggravated by anxiety
      sensitivity and somatosensory amplification. As advanced PAP therapy modes (ie,
      auto-bilevel PAP [ABPAP] or adaptive servo-ventilation [ASV]) may address these
      side effects, we hypothesized such treatment would be associated with decreased
      expiratory intolerance and increased adherence in posttraumatic stress patients
      with co-occurring OSA. Methods: We reviewed charts of 147 consecutive adult
      patients with moderately severe posttraumatic stress symptoms and objectively
      diagnosed OSA. All patients failed or rejected CPAP and were manually titrated on
      auto-adjusting, dual-pressure ABPAP or ASV modes in the sleep laboratory, a
      technique to eliminate flow limitation breathing events while resolving EPI.
      Patients were then prescribed either mode of therapy. Follow-up encounters
      assessed patient use, and objective data downloads (ODDs) measured adherence.
      Results: Of 147 charts reviewed, 130 patients were deemed current PAP users, and
      102 provided ODDs: 64 used ASV and 38 used ABPAP. ODDs yielded three groups: 59
      adherent per insurance conventions, 19 subthreshold compliant partial users, and
      24 noncompliant. Compliance based on available downloads was 58%, notably higher
      than recently reported rates in PTSD patients with OSA. Among the 19 partial
      users, 17 patients were minutes of PAP use or small percentages of nights removed
      from meeting insurance compliance criteria for PAP devices. Conclusion: Research
      is warranted on advanced PAP modes in managing CPAP failure in PTSD patients with
      comorbid OSA. Subthreshold adherence constructs may inform clinical care in a
      patient-centric model distinct from insurance conventions. Speculatively,
      clinical application of this transitional zone ("subthreshold" number of hours)
      may increase PAP use and eventual adherence.

PMID- 29200834
TI  - Effects of patients' motives in choosing a provider on determining the type of
      medical institution.
AB  - Background: Primary care is relatively weak in the Republic of Korea. As the
      referral system is not well established, patients can freely choose from among
      clinics, hospitals, and tertiary hospitals. This study was conducted to determine
      the factors influencing patients' choice of providers. Methods: A survey was
      conducted of 999 Korean adults aged 19-59 years. An exploratory factor analysis
      was performed on nine factors influencing their motives in choosing a medical
      provider. The factors derived from this analysis and the types of medical
      institutions were used as the independent and dependent variables, respectively,
      in logistic regression analysis. Adjustments were made for region, gender, age,
      educational level, income, type of insurance, and chronic diseases. Results: The
      results showed that patients preferred clinics when considering the importance of
      accessibility, staff kindness, and patient-centeredness; they preferred hospitals
      when considering cleanliness; and tertiary hospitals when considering the
      reputation and structural factors. When considering structural factors, clinics
      and hospitals were less preferred; however tertiary hospitals were less preferred
      when considering accessibility, staff kindness, and patient-centeredness.
      Conclusion: It is necessary to provide more accessible and patient-centered
      services in order to strengthen the primary health care role of clinics. In
      addition, efforts are needed to improve the quality of health care of tertiary
      hospitals in order to meet patient expectations.

PMID- 29200835
TI  - Transitional-aged youth perceptions of influential factors for substance-use
      change and treatment seeking.
AB  - There is an evident disparity between the number of youth who report experiencing
      problematic substance use and the number who seek treatment. To address this
      disparity, it is important to understand the reasons youth do and do not seek
      substance use treatment. Using qualitative data obtained from semistructured
      interviews with 31 youth aged 17-25 years presenting for treatment at a mental
      health hospital, the current study identifies themes in the factors that youth
      identify as having influenced them to seek or delay treatment. In alignment with
      self-determination theory, youth identified internal factors, such as wanting to
      better their academic, social, or financial situation, and external factors, such
      as familial pressure, as motivating them to seek treatment. Factors beyond those
      encompassed by self-determination theory were also revealed as having influenced
      youth decisions to seek treatment for substance abuse. These predominantly
      included structural factors, including satisfaction with previous treatment,
      accessibility of services, and availability of clinicians. These findings provide
      important insight for first-contact professionals and service providers looking
      to enhance youth motivation to seek and engage in treatment. Limitations and
      opportunities for future research are discussed.

PMID- 29200836
TI  - Computerized cognitive stimulation and engagement programs in older adults with
      mild cognitive impairment: comparing feasibility, acceptability, and cognitive
      and psychosocial effects.
AB  - Purpose: Mild cognitive impairment (MCI) is associated with a higher risk of
      dementia and is becoming a topic of interest for pharmacological and
      nonpharmacological interventions. With advances in technology, computer-based
      cognitive exercises are increasingly integrated into traditional cognitive
      interventions, such as cognitive training. Another type of cognitive intervention
      involving technology use is cognitive engagement, consisting of involving
      participants in highly motivational and mentally challenging activities, such as
      learning to use a form of new digital technology. This study examined the
      feasibility and acceptability of a computerized cognitive stimulation (CCS)
      program and a computerized cognitive engagement (CCE) program, and then compared
      their effects in older adults with MCI. Patients and methods: In this randomized
      study, data from 19 MCI patients were analyzed (n=9 in CCS and n=10 in CCE). The
      patients attended a group weekly session for a duration of 3 months. Assessments
      of cognitive and psychosocial variables were conducted at baseline (M0) and at
      the end of the programs (M3). Results: All of the participants attended the 12
      sessions and showed a high level of motivation. Attrition rate was very low (one
      dropout at M3 assessment). At M3, the CCS participants displayed a significant
      improvement in part B of the Trail Making Test (TMT-B; p=0.03) and self-esteem
      (p=0.005), while the CCE participants showed a significant improvement in part A
      of the Trail Making Test (TMT-A; p=0.007) and a higher level of technology
      acceptance (p=0.006). The two groups did not differ significantly (p>0.05) in
      cognitive and psychosocial changes after the intervention. However, medium effect
      sizes (Cohen's d=0.56; 95% CI =-0.43:1.55) were found on the free recall,
      favoring the CCS group, as well as on TMT-A (d=0.51; 95% CI =-0.48:1.49) and
      technology acceptance (d=-0.65; 95% CI =-1.64:0.34), favoring the CCE group.
      Conclusion: Both interventions were highly feasible and acceptable and allowed
      improvement in different aspects of cognitive and psychosocial functioning in MCI
      subjects.

PMID- 29200837
TI  - The relationship of SSRI and SNRI usage with interstitial lung disease and
      bronchiectasis in an elderly population: a case-control study.
AB  - Background: The association between interstitial lung disease (ILD) and selective
      serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors
      (SSRI/SNRI) has been previously described in published case reports. However, its
      prevalence may be more common than expected. We examined the association between
      SSRI/SNRI usage and presence of ILD and or bronchiectasis (ILD/B) in an elderly
      population. Methods: We conducted a retrospective case series and case-control
      study involving all 296 eligible elderly patients in one primary care geriatric
      practice in Victoria, BC, Canada. Cases required the presence of ILD/B on
      computed tomography (CT) or chest X-ray (CXR). Cases were excluded if they had
      other causes for ILD/B on CXR or CT such as exposure to known pneumotoxic drugs,
      metastatic cancer, rheumatoid lung disease, sarcoidosis, previous pulmonary
      tuberculosis, or pneumoconiosis. Data were abstracted from the patients' medical
      record. The exposure variable was standardized cumulative person-month (p-m) dose
      of SSRI/SNRI. The study was approved by the Clinical Research Ethics Board of
      University of British Columbia with a waiver of informed consent. Results: A
      total of 12 cases and 273 controls were identified. Their mean ages were 89.0 and
      88.7 years, respectively (p=0.862). A total of 10/12 cases and 99/273 controls
      were exposed to SSRI/SNRI. The odds ratio was 8.79, 95% confidence interval 2.40
      32.23 (p=0.001). The median p-m exposure to SSRI/SNRI was 110.0 months for cases
      and 29.5 for controls (p=0.003). Conclusion: SSRIs and SNRIs were significantly
      associated with the risk of ILD/B in this elderly population. Because of their
      widespread usage, further studies should be done to validate these findings.
      Prescribers should cautiously monitor patients for development of insidious
      pulmonary symptoms when these drugs are used.

PMID- 29200838
TI  - Mortality after major amputation in elderly patients with critical limb ischemia.
AB  - Background: Owing to the aging population, the number of elderly patients with
      critical limb ischemia (CLI) has increased. The consequence of amputation is
      immense. However, at the moment, information about the mortality after amputation
      in the elderly vascular patients is unknown. For this reason, this study
      evaluated mortality rates and patient-related factors associated with mortality
      after a major amputation in elderly patients with CLI. Methods: From 2006 to
      2013, we included patients aged >70 years who were treated for chronic CLI by
      primary or secondary major amputation within or after 3 months of initial therapy
      (revascularization or conservative management). Outcome measurements were
      mortality after major amputation and factors associated with mortality (age,
      comorbidity and timing of amputation). Results: In total, 168/651 patients (178
      legs; 26%) underwent a major amputation. Patients were stratified by age: 70-80
      years (n=86) and >80 years (n=82). Overall mortality after major amputation was
      44%, 66% and 85% after 1, 3 and 5 years, respectively. The 6-month and 1-year
      mortality in patients aged 80 years or older was, respectively, 59% or 63% after
      a secondary amputation <3 months versus 34% and 44% after a secondary amputation
      >3 months. Per year of age, the mortality rate increased by 4% (P=0.005). No
      significant difference in mortality after major amputation was found in the
      presence of comorbidity or according to Rutherford classification. Conclusion:
      Despite developments in the treatment of CLI by revascularization, amputation
      rates remain high and are associated with tremendous mortality rates. Secondary
      amputation after a failed attempt of revascularization causes a higher mortality.
      Further research concerning timing of amputation and patient-related outcome is
      needed to evaluate if selected patients might benefit from primary amputation.

PMID- 29200839
TI  - Prediction of risk of depressive symptoms in menopausal women based on hot flash
      and sweating symptoms: a multicentre study.
AB  - Objective: The present study aimed to develop a symptom-based (namely, hot
      flashes and sweating) scoring system for predicting the risk of depressive
      symptoms in menopausal women via a multicentre cross-sectional survey. Methods:
      The data examined in the present study were obtained from 1,004 women aged 40-60
      years who underwent physical examination at A Hospital. The basic information was
      obtained using a questionnaire-based survey. A self-rating depression scale was
      used to obtain the depressive symptom scores, while the Kupperman Menopausal
      Index was used to obtain the scores for the frequency of hot flashes and
      sweating. A logistic regression model was also established. The resulting beta
      coefficient was employed to calculate and predict the risk of depressive symptoms
      in these women and a risk scoring system was established. The scoring system was
      validated using samples from 2 other centers (validation sample 1: B Hospital,
      440 women; validation sample 2: C Hospital, 247 women). Results: The scoring
      system developed to predict the risk of depressive symptoms in menopausal women
      was based on hot flash and sweating symptoms and associated with menopausal
      status, hot flash scores, education level (high school education and below) and
      being diabetic. The scoring system yielded a total score of 0-54 points. For
      women in the study sample, the area under the curve (AUC) of depressive symptom
      risk score was 0.750 (95% CI, 0.708-0.793). Validation sample 1 had an AUC of
      0.731 (95% CI, 0.667-0.794), while validation sample 2 had an AUC of 0.744 (95%
      CI, 0.669-0.820). The optimal cut-off score to assess depressive symptoms in
      women participating in the present study was 31 points. The sensitivity and
      specificity for predicting depressive symptoms in the study sample were 0.667 and
      0.701, respectively. In contrast, the sensitivity was 0.840 in validation sample
      1 and 0.879 in validation sample 2. Conclusion: The hot flash and sweating
      symptom-based scoring system developed to predict the risk of depressive symptoms
      in menopausal women relies on non-laboratory survey data. The system is simple,
      practical, and convenient to use. For Chinese huge population of menopausal
      women, the scoring system should be considered a reliable screening tool for
      depressive symptoms.

PMID- 29200840
TI  - Lung function and long-term safety of tiotropium/olodaterol in East Asian
      patients with chronic obstructive pulmonary disease.
AB  - Background and purpose: While the efficacy and safety of combined tiotropium and
      olodaterol in patients with COPD was established in a large clinical trial
      program, it is important to assess whether clinical data can be applied to
      geographic patient groups, particularly for East Asian patients who may have a
      different phenotypic profile to the global trial population. This study aimed to
      compare the lung function and safety profiles of tiotropium/olodaterol and
      monocomponents in East Asian and global populations from the TONADO(r) trials.
      Materials and methods: In the replicate, double-blind, parallel-group, active
      controlled, randomized, 52-week, Phase III TONADO studies, patients received
      tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced
      expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0
      3) response and trough FEV1 response at 24 weeks for the approved doses,
      tiotropium/olodaterol 5/5 MUg, tiotropium 5 MUg, and olodaterol 5 MUg. Treatment
      emergent adverse events were recorded throughout treatment and <=21 days after
      study medication. Results: In the East Asian population, 1,152 patients were
      randomized (5,163 overall). After 24 weeks, FEV1 AUC0-3 and trough FEV1 responses
      were greater (P<0.0001) with tiotropium/olodaterol 5/5 MUg in both populations
      versus tiotropium or olodaterol. The East Asian population showed slightly
      greater trough FEV1 treatment differences between tiotropium/olodaterol 5/5 MUg
      and tiotropium compared to the overall population. Generally, no increase in
      adverse events was seen with tiotropium/olodaterol 5/5 MUg compared to tiotropium
      and olodaterol in either population. Conclusion: The efficacy and safety profile
      of tiotropium/olodaterol 5/5 MUg has been demonstrated for both East Asian and
      global populations.

PMID- 29200841
TI  - MAPK/FoxA2-mediated cigarette smoke-induced squamous metaplasia of bronchial
      epithelial cells.
AB  - Objective: To explore the effect of cigarette smoke (CS) on the development of
      squamous metaplasia in human airway epithelial cells and the role of MAPK- and
      FoxA2-signaling pathways in the process. Materials and methods: In an in vitro
      study, we treated the bronchial epithelial cell line BEAS2B with CS extract,
      followed by treatment with the ERK inhibitor U0126, the JNK inhibitor SP600125,
      or the p38 inhibitor SB203580. In vivo, we used a CS-induced rat model. After
      treatment with CS with or without MAPK inhibitors for 90 days, lung tissues were
      harvested. p-ERK, p-p38 and p-JNK protein levels in cells and lung tissue were
      measured using enzyme-linked immunosorbent assays, mRNA- and protein-expression
      profiles of FoxA2, E-cadherin, CD44, and ZO1 were measured using quantitative
      real-time polymerase chain reaction and Western blotting, respectively, and
      morphological changes in bronchial epithelial cells were observed using lung
      tissue staining. Results: In both the in vitro and in vivo studies,
      phosphorylation of the ERK1/2, JNK, and p38 proteins was significantly increased
      (P<0.05) and mRNA and protein expression of E-cadherin and FoxA2 significantly
      decreased (P<0.05) compared with the control group. ERK, JNK, and p38 inhibitors
      reversed the CS-extract-induced changes in E-cadherin, CD44, and ZO1 mRNA and
      protein expression (P<0.05), decreased p-ERK, p-p38, and p-JNK protein levels in
      cells and lung tissue, suppressed bronchial epithelial hyperplasia and local
      squamous metaplasia, and decreased FoxA2 expression. Conclusion: MAPK and FoxA2
      mediate CS-induced squamous metaplasia. MAPK inhibitors upregulate FoxA2,
      resulting in a reduction in the degree of squamous metaplasia.

PMID- 29200842
TI  - Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD
      and pulmonary hypertension.
AB  - Studies have shown that vasodilators such as iloprost can be useful for treating
      pulmonary hypertension (PH). However, in patients with COPD, vasodilators may
      inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy
      and safety of iloprost inhalation was assessed in 67 patients with PH associated
      with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37
      patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP
      25-35 mmHg with low cardiac index [<2.0 L?min-1?m-2]). All patients received a
      single 20 ug dose of iloprost via a nebulizer (4.4 ug delivered at the
      mouthpiece). No serious adverse events were reported. Hemodynamic and gas
      exchange parameters (arterial blood gas and shunt fraction [Qs/Qt]) were measured
      or calculated at baseline and 10 min after iloprost inhalation. mPAP decreased by
      2.1 mmHg (95% CI, -3.3 to -1.0), pulmonary vascular resistance (PVR) decreased by
      62.4 dyn?s?cm-5 (95% CI, -92.9 to -31.8), and cardiac output increased by 0.4
      L?min-1 (95% CI, 0.2-0.5). There was a more significant decline in PVR in
      patients with severe COPD-PH than in those with nonsevere COPD-PH. Hypoxemia and
      intrapulmonary shunt were more extreme in patients with severe COPD-PH. However,
      there were no significant differences in arterial blood gas and Qs/Qt between
      patients with nonsevere and severe forms of COPD-PH. In conclusion, iloprost
      improved pulmonary hemodynamics without detrimental effects on arterial
      oxygenation in patients with COPD-PH, even in those with severe PH. These
      findings suggest that the short-term use of iloprost in patients with COPD-PH is
      effective and well tolerated.

PMID- 29200843
TI  - Eosinophilic and non-eosinophilic COPD patients with chronic respiratory failure:
      neutrophil-to-lymphocyte ratio as an exacerbation marker.
AB  - Aim: Increased dyspnea, sputum volume, and purulence are subjective symptoms in
      COPD patients. To diagnose COPD exacerbations with chronic respiratory failure
      (CRF) and to assess the requirement for antibiotic treatment, physicians require
      more objective criteria. We aimed to investigate whether neutrophil-to-lymphocyte
      ratio (NLR) can be used as an infectious exacerbation marker in COPD patients
      with CRF. Patients and methods: This retrospective cross-sectional study was
      performed in the intensive care outpatient clinic of a tertiary training hospital
      between 2014 and 2015. Patients admitted with CRF due to COPD and who had
      complete blood count (CBC) results were enrolled. CBC results and C-reactive
      protein (CRP) levels were obtained from the hospital online database. The
      "modified exacerbation model (MEM)" was defined as follows: exacerbation A,
      leukocytes >=12,000/mm3, CRP >10 mg/dL; exacerbation B, leukocytes >=10,000/mm3,
      CRP >10 mg/dL; exacerbation C, leukocytes >=10,000/mm3, CRP >8 mg/dL;
      exacerbation D, leukocytes >=10,000/mm3, CRP >5 mg/dL. The cutoff value of NLR
      was defined for each model. Patients were split into two groups based on the NLR
      cutoff value according to the "NLR exacerbation model" and further subgrouped
      according to peripheral eosinophil percentage (eosinophils >=2% and <2%) and
      compared with the MEM. Results: A total of 1,066 COPD patients (430 females,
      40.3%), with a mean age of 66+/-13 years, were included. A NLR cutoff value of
      3.54 (NLR >=3.54, n=366, 34%) showed the highest sensitivity and specificity for
      model A (78%, 69%), model B (63%, 71%), model C (61%, 72%), and model D (58%,
      72%). Peripheral eosinophilia (PE >=2%) was present in 48 patients (4.5%). The
      ratio of patients with PE <2% in the NLR >=3.54 group was significantly higher in
      the MEM (P<0.001). Conclusion: The NLR presents an attractive option as an
      exacerbation marker in COPD patients with CRF due to its simplicity and cost
      effectiveness. In COPD patients with CRF, where the NLR is >=3.54, PE levels are
      <2%, and subjective symptoms are present, antibiotic treatment should be
      considered.

PMID- 29200844
TI  - Down-top nanofabrication of binary (CdO)x (ZnO)1-x nanoparticles and their
      antibacterial activity.
AB  - In the present study, binary oxide (cadmium oxide [CdO])x (zinc oxide [ZnO])1-x
      nanoparticles (NPs) at different concentrations of precursor in calcination
      temperature were prepared using thermal treatment technique. Cadmium and zinc
      nitrates (source of cadmium and zinc) with polyvinylpyrrolidone (capping agent)
      have been used to prepare (CdO)x (ZnO)1-x NPs samples. The sample was
      characterized by X-ray diffraction (XRD), scanning electron microscopy, energy
      dispersive X-ray (EDX), transmission electron microscopy (TEM), and Fourier
      transform infrared (FTIR) spectroscopy. XRD patterns analysis revealed that NPs
      were formed after calcination, which showed a cubic and hexagonal crystalline
      structure of (CdO)x (ZnO)1-x NPs. The phase analysis using EDX spectroscopy and
      FTIR spectroscopy confirmed the presence of Cd and Zn as the original compounds
      of prepared (CdO)x (ZnO)1-x NP samples. The average particle size of the samples
      increased from 14 to 33 nm as the concentration of precursor increased from
      x=0.20 to x=0.80, as observed by TEM results. The surface composition and valance
      state of the prepared product NPs were determined by X-ray photoelectron
      spectroscopy (XPS) analyses. Diffuse UV-visible reflectance spectra were used to
      determine the optical band gap through the Kubelka-Munk equation; the energy band
      gap was found to decrease for CdO from 2.92 to 2.82 eV and for ZnO from 3.22 to
      3.11 eV with increasing x value. Additionally, photoluminescence (PL) spectra
      revealed that the intensity in PL increased with an increase in particle size. In
      addition, the antibacterial activity of binary oxide NP was carried out in vitro
      against Escherichia coli ATCC 25922 Gram (-ve), Salmonella choleraesuis ATCC
      10708, and Bacillus subtilis UPMC 1175 Gram (+ve). This study indicated that the
      zone of inhibition of 21 mm has good antibacterial activity toward the Gram
      positive B. subtilis UPMC 1175.

PMID- 29200845
TI  - Solid lipid nanoparticles for thermoresponsive targeting: evidence from
      spectrophotometry, electrochemical, and cytotoxicity studies.
AB  - Thermoresponsive drug delivery systems are designed for the controlled and
      targeted release of therapeutic payload. These systems exploit hyperthermic
      temperatures (>39 degrees C), which may be applied by some external means or due
      to an encountered symptom in inflammatory diseases such as cancer and arthritis.
      The objective of this paper was to provide some solid evidence in support of the
      hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive
      targeting by undergoing solid-liquid phase transition at their melting point
      (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid
      natural fatty acids, and their MP was measured by differential scanning
      calorimetry (DSC). SLNs (MP 39 degrees C) containing 5-fluorouracil (5-FU) were
      synthesized by hot melt encapsulation method, and were found to have spherical
      shape (transmission electron microscopy studies), desirable size (<200 nm), and
      enhanced physicochemical stability (Fourier transform infrared spectroscopy
      analysis). We observed a sustained release pattern (22%-34%) at 37 degrees C (5
      hours). On the other hand, >90% drug was released at 39 degrees C after 5 hours,
      suggesting that the SLNs show thermoresponsive drug release, thus confirming our
      hypothesis. Drug release from SLNs at 39 degrees C was similar to oleic acid and
      linoleic acid nanoemulsions used in this study, which further confirmed that
      thermoresponsive drug release is due to solid-liquid phase transition. Next, a
      differential pulse voltammetry-based electrochemical chemical detection method
      was developed for quick and real-time analysis of 5-FU release, which also
      confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found
      to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded
      SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed
      thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity
      was higher at 39 degrees C (cell viability 72%-78%) compared to 37 degrees C
      (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a
      safe, simple, and effective platform for thermoresponsive targeting.

PMID- 29200846
TI  - Improved resection and prolonged overall survival with PD-1-IRDye800CW
      fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse
      model.
AB  - An intraoperative technique to accurately identify microscopic tumor residuals
      could decrease the risk of positive surgical margins. Several lines of evidence
      support the expression and immunotherapeutic effect of PD-1 in breast cancer.
      Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast
      tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody
      (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1
      IRDye800CW was developed and examined for its application in tumor imaging and
      image-guided tumor resection in an immunocompetent 4T1 mouse tumor model.
      Fluorescence molecular imaging was performed to monitor probe biodistribution and
      intraoperative imaging. Bioluminescence imaging was performed to monitor tumor
      growth and evaluate postsurgical tumor residuals, recurrences, and metastases.
      The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with
      the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1
      adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and
      thus improved survival rate. Our study demonstrates the feasibility of using PD-1
      IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover,
      PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases
      emanating from tumor residuals.

PMID- 29200847
TI  - mPEG-PLA/TPGS mixed micelles via intranasal administration improved the
      bioavailability of lamotrigine in the hippocampus.
AB  - Purpose: This study aimed to develop a novel methoxy poly(ethylene glycol)
      poly(lactide) (mPEG-PLA)/D-alpha-tocopherol polyethylene glycol 1000 succinate
      (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG)
      distribution in the hippocampus. Methods: LTG-loaded mPEG-PLA/TPGS mixed micelles
      and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics,
      particle size, surface morphology, and release behavior in vitro were researched.
      Then, a microdialysis sampling technique coupled with two validated
      chromatographic systems was developed for the continuous measurement of the
      protein-unbound form of LTG in the rat plasma and hippocampus after administering
      two kinds of micelles and LTG solution intranasally. Results: The drug loading
      and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with
      optimal formulation were 36.44%+/-0.14%, 39.28%+/-0.26%, 122.9, and 183.5 nm,
      respectively, with a core-shell structure. The cumulative release rate in vivo of
      LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained
      release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and
      area under concentration-time curve from zero to time of last quantifiable
      concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles
      were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min?MUg)/L in
      the hippocampus, respectively. Conclusion: The results revealed that LTG-loaded
      mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity
      and reduced the efflux of LTG in the brain, suggesting that the function of TPGS
      inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the
      potential to overcome refractory epilepsy.

PMID- 29200849
TI  - Erratum: Delivery of curcumin by directed self-assembled micelles enhances
      therapeutic treatment of non-small-cell lung cancer [Corrigendum].
AB  - [This corrects the article on p. 2621 in vol. 12, PMID: 28435247.].

PMID- 29200848
TI  - Encapsulation of Piper cabralanum (Piperaceae) nonpolar extract in poly(methyl
      methacrylate) by miniemulsion and evaluation of increase in the effectiveness of
      antileukemic activity in K562 cells.
AB  - This study aimed to synthesize and characterize nanoparticles (NPs) of
      poly(methyl methacrylate) (PMMA) and evaluate their ability to incorporate plant
      extracts with antitumor activity and low dissolution in aqueous media. The
      extract used was n-hexane partition of the methanol extract of Piper cabralanum
      (PCA-HEX). PMMA NPs were obtained using the mini-emulsion method, which was able
      to encapsulate almost 100% of PCA-HEX. The synthesized polymeric particles
      presented with a size of 200 nm and a negative charge. Cytotoxicity tests by MTT
      and trypan blue assays showed that NPs without PCA-HEX did not kill leukemic
      cells (K562 cells). NPs containing PCA-HEX were able to enhance cell death when
      compared to pure extract. The results showed that PMMA NPs could be useful as a
      drug delivery system as they can enhance the antitumor activity of the PCA-HEX
      extract by more than 20-fold. PMMA NPs containing plant extracts with antitumor
      activities may be an alternative to control the evolution of diseases such as
      leukemia.

PMID- 29200850
TI  - Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of
      allergen.
AB  - Immunotherapy by sublingual administration of allergens provides high patient
      compliance and has emerged as an alternative to subcutaneous immunotherapy for
      the treatment of IgE-associated allergic diseases. However, sublingual
      immunotherapy (SLIT) can cause adverse events. Development of allergen delivery
      systems enabling more efficient delivery and hence lower allergen load might
      reduce the adverse events. In the present study, we have investigated neutral and
      cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen,
      in an OVA-induced allergic airway inflammation model. We investigated the
      liposome carriers' ability to improve tolerance induction of antigens compared to
      the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks
      with free or liposome encapsulated OVA followed by intraperitoneal injections and
      intranasal challenge. Mice sublingually treated with OVA-liposomes showed a
      significant reduction of airway eosinophilia and splenocyte proliferation in
      comparison to free OVA. A similar nonsignificant pattern was seen for OVA
      specific IgE antibodies. In addition, reduced levels of interferon-gamma and
      interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome
      treated mice compared to the sham-treated group. In conclusion, in vivo efficacy
      data showed that prophylactic SLIT with OVA-liposomes is significantly more
      effective in preventing allergic inflammation than the corresponding dose of free
      OVA.

PMID- 29200851
TI  - Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine
      application.
AB  - In this review, specific attention is paid to the development of nanostructured
      magnetic hydroxyapatite (MHAp) and its potential application in controlled
      drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the
      development of contrast agents for magnetic resonance imaging. Both magnetite and
      hydroxyapatite materials have excellent prospects in nanomedicine with
      multifunctional therapeutic approaches. To date, many research articles have
      focused on biomedical applications of nanomaterials because of which it is very
      difficult to focus on any particular type of nanomaterial. This study is possibly
      the first effort to emphasize on the comprehensive assessment of MHAp
      nanostructures for biomedical applications supported with very recent
      experimental studies. From basic concepts to the real-life applications, the
      relevant characteristics of magnetic biomaterials are patented which are briefly
      discussed. The potential therapeutic and diagnostic ability of MHAp
      nanostructured materials make them an ideal platform for future nanomedicine. We
      hope that this advanced review will provide a better understanding of MHAp and
      its important features to utilize it as a promising material for multifunctional
      biomedical applications.

PMID- 29200852
TI  - Natural material-decorated mesoporous silica nanoparticle container for
      multifunctional membrane-controlled targeted drug delivery.
AB  - To avoid the side effects caused by nonspecific targeting, premature release,
      weak selectivity, and poor therapeutic efficacy of current nanoparticle-based
      systems used for drug delivery, we fabricated natural material-decorated
      nanoparticles as a multifunctional, membrane-controlled targeted drug delivery
      system. The nanocomposite material coated with a membrane was biocompatible and
      integrated both specific tumor targeting and responsiveness to stimulation, which
      improved transmission efficacy and controlled drug release. Mesoporous silica
      nanoparticles (MSNs), which are known for their biocompatibility and high drug
      loading capacity, were selected as a model drug container and carrier. The
      membrane was established by the polyelectrolyte composite method from chitosan
      (CS) which was sensitive to the acidic tumor microenvironment, folic acid
      modified CS which recognizes the folate receptor expressed on the tumor cell
      surface, and a CD44 receptor-targeted polysaccharide hyaluronic acid. We
      characterized the structure of the nanocomposite as well as the drug release
      behavior under the control of the pH-sensitive membrane switch and evaluated the
      antitumor efficacy of the system in vitro. Our results provide a basis for the
      design and fabrication of novel membrane-controlled nanoparticles with improved
      tumor-targeting therapy.

PMID- 29200853
TI  - Development and in vitro evaluations of new decitabine nanocarriers for the
      treatment of acute myeloid leukemia.
AB  - Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is
      used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged
      >=65 years. However, it can only be administered intravenously due to very low
      oral bioavailability and a large distribution volume. Oral administration would
      allow outpatient treatment, improving quality of life and reducing treatment
      costs. The present study proposes to develop lipid nanocapsules (LNCs),
      originally designed for lipophilic drugs, to encapsulate decitabine. Two
      different formulations of LNCs were designed: LNCs based on a high proportion of
      Transcutol(r) HP (THP-LNCs) and LNCs associated with a mixture of Transcutol(r)
      HP and Tween(r) 80 (THP-T80-LNCs). The second formulation had a diameter of
      26.5+/-0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472+/
      64 ug/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML
      cell lines depending on their decitabine resistance: HEL (not resistant) and HL
      60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also
      evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL
      60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent
      permeability on Caco-2 cell monolayers was also increased, suggesting a
      potentially useful formulation to increase the oral bioavailability of
      decitabine.

PMID- 29200854
TI  - Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of
      posterior lumbar interbody fusion with cages for degenerative lumbar disease in
      osteoporosis patients by downregulating serum miR-155.
AB  - Degenerative lumbar disease (DLD) is a significant issue for public health.
      Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion
      rate and realignment on DLD. However, there are some complications following the
      surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory
      activities and may be suitable for infection therapy. MiR-155 is a biomarker
      associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy
      by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of
      alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six
      DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group
      (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg
      pluronic nanoparticles). Serum miR-155 level was measured by real-time
      quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH),
      aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin
      1beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) were measured.
      Weighted mean difference (WMD), relative risk (RR), complications, surgery
      infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores
      were used to evaluate therapeutic efficacy. After 1-month therapy, infection
      rates and side effects were lower in OG than those in PG (RR =0.64, 95%
      confidence interval [CI] [0.48, 0.84], P=0.001). The fusion rates were higher in
      OG than in PG (WMD =21.96, 95% CI [-0.24, 37.62], P=0.021). The JOA scores were
      higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], P=0.007), and no
      significant difference was found for the visual analog scale and Oswestry
      Disability Index. Serum levels of miR-155, ALT, AST, and IL-1beta were lower
      while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased
      the levels of ALT, AST, and IL-1beta and reduced the levels of SOD, GSH, and IL
      1ra. In contrast, miR-155 inhibitor had reverse results. Therefore, ONAS has
      better improvement in complications and therapeutic effects on DLD by regulating
      serum miR-155.

PMID- 29200855
TI  - Vascular thrombus imaging in vivo via near-infrared fluorescent nanodiamond
      particles bioengineered with the disintegrin bitistatin (Part II).
AB  - The aim of this feasibility study was to test the ability of fluorescent
      nanodiamond particles (F-NDP) covalently conjugated with bitistatin (F-NDP-Bit)
      to detect vascular blood clots in vivo using extracorporeal near-infrared (NIR)
      imaging. Specifically, we compared NIR fluorescence properties of F-NDP with N-V
      (F-NDPNV) and N-V-N color centers and sizes (100-10,000 nm). Optimal NIR
      fluorescence and tissue penetration across biological tissues (rat skin, porcine
      axillary veins, and skin) was obtained for F-NDPNV with a mean diameter of 700
      nm. Intravital imaging (using in vivo imaging system [IVIS]) in vitro revealed
      that F-NDPNV-loaded glass capillaries could be detected across 6 mm of rat red
      muscle barrier and 12 mm of porcine skin, which equals the average vertical
      distance of a human carotid artery bifurcation from the surface of the adjacent
      skin (14 mm). In vivo, feasibility was demonstrated in a rat model of occlusive
      blood clots generated using FeCl3 in the carotid artery bifurcation. Following
      systemic infusions of F-NDPNV-Bit (3 or 15 mg/kg) via the external carotid artery
      or femoral vein (N=3), presence of the particles in the thrombi was confirmed
      both in situ via IVIS, and ex vivo via confocal imaging. The presence of F-NDPNV
      in the vascular clots was further confirmed by direct counting of fluorescent
      particles extracted from clots following tissue solubilization. Our data suggest
      that F-NDPNV-Bit associate with vascular blood clots, presumably by binding of F
      NDPNV-Bit to activated platelets within the blood clot. We posit that F-NDPNV-Bit
      could serve as a noninvasive platform for identification of vascular thrombi
      using NIR energy monitored by an extracorporeal device.

PMID- 29200856
TI  - Altered microstructure of brain white matter in females with anorexia nervosa: a
      diffusion tensor imaging study.
AB  - Objective: Structural studies have reported anorexia nervosa (AN) patients with
      abnormal gray matter in several brain regions and dysfunction in some connected
      neural circuits. However, the role of white matter (WM) in AN patients has rarely
      been investigated. The present study aimed to assess alterations in WM
      microstructure of the entire brain in females with AN using a voxel-based method
      on diffusion tensor imaging (DTI) data. Materials and methods: The study enrolled
      8 female patients with AN and 14 age-matched females as controls (CW). The DTI
      data was collected from each subject to calculate the fractional anisotropy (FA)
      maps of the whole brain by the DTI-Studio software. Subsequently, a 2-sample t
      test (P<0.05, corrected) was performed to detect the difference in FA maps of AN
      and CW group, and a Pearson's correlation analyzed the relationship between mean
      FA value of brain regions and body mass index (BMI). Results: Compared with CW,
      AN patients revealed a significant decrease in FA maps in the left superior
      frontal gyrus, medial frontal gyrus, anterior cingulate cortex, middle frontal
      gyrus, inferior frontal gyrus, thalamus, and bilateral insula. Moreover,
      significantly positive correlations were established between the mean FA value of
      the left inferior frontal gyrus, insula as well as thalamus and BMI in AN
      patients. Conclusions: Our findings supported the presence of WM abnormality in
      patients with AN. The significant differences of FA maps, in patients with AN,
      were associated with their aberrant BMI. The results further improved our
      understanding of the pathophysiological mechanisms underlying AN.

PMID- 29200857
TI  - Reversal of olanzapine-induced weight gain in a patient with schizophrenia by
      switching to asenapine: a case report.
AB  - Aims: Antipsychotics are effective for treating schizophrenia, but atypical
      antipsychotics can cause several adverse side effects including weight gain,
      hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases
      the risk of metabolic diseases. Methods: We treated a case of olanzapine-induced
      weight gain in a 41-year-old man with schizophrenia by switching his medication
      from olanzapine to asenapine. Results: The weight gain improved after switching
      the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no
      significant worsening of psychological symptoms or other adverse effects.
      Conclusions: Asenapine might be effective for treating patients with
      schizophrenia who experience olanzapine-induced weight gain.

PMID- 29200858
TI  - Group cognitive-behavioral therapy in insomnia: a cross-sectional case-controlled
      study.
AB  - Background: Group cognitive-behavioral therapy (GCBT) might meet the considerable
      treatment demand of insomnia, but its effectiveness needs to be addressed.
      Participants: This study recruited 27 insomnia patients treated with 16-weeks of
      zolpidem (zolpidem group), 26 patients treated with 4-weeks of zolpidem and also
      treated with 12-weeks of GCBT (GCBT group), and 31 healthy control volunteers.
      Methods: Before treatment and 16 weeks after intervention, participants were
      evaluated using the Patient Health Questionnaires (Patient Health Questionnaire-9
      [PHQ-9] and Patient Health Questionnaire-15 [PHQ-15]), the Dysfunctional Beliefs
      and Attitudes about Sleep-16 (DBAS-16), and the Pittsburgh Sleep Quality Index
      (PSQI). Results: Compared to the zolpidem and healthy control groups, the scale
      scores of PHQ-9, PHQ-15, DBAS-16 and PSQI were significantly reduced after
      intervention in the GCBT group. Regarding the score changes, there were
      correlations between PSQI, DBAS-16, PHQ-9, and PHQ-15 scales in the zolpidem
      group, but there were limited correlations between PSQI and some DBAS-16 scales
      in the GCBT group. Conclusion: Our results indicate that GCBT is effective to
      treat insomnia by improving sleep quality and reducing emotional and somatic
      disturbances; thus, the study supports the advocacy of applying group
      psychotherapy to the disorder.

PMID- 29200859
TI  - Abnormal regional spontaneous neural activity in visual pathway in retinal
      detachment patients: a resting-state functional MRI study.
AB  - Objective: The aim of the study was to investigate changes of brain neural
      homogeneity in retinal detachment (RD) patients using the regional homogeneity
      (ReHo) method to understand their relationships with clinical features. Materials
      and methods: A total of 30 patients with RD (16 men and 14 women), and 30 healthy
      controls (HCs) (16 men and 14 women) closely matched in age and sex were
      recruited. Resting-state functional magnetic resonance imaging scans were
      performed for all subjects. The ReHo method was used to investigate the brain
      regional neural homogeneity. Patients with RD were distinguished from HCs by
      receiver operating characteristic curve. The relationships between the mean ReHo
      signal values in many brain regions and clinical features in RD patients were
      calculated by Pearson correlation analysis. Results: Compared with HCs, RD
      patients had significantly decreased ReHo values in the right occipital lobe,
      right superior temporal gyrus, bilateral cuneus and left middle frontal gyrus.
      Moreover, we found that the mean ReHo signal of the bilateral cuneus showed
      positive relationships with the duration of the RD (r=0.392, P=0.032).
      Conclusion: The RD patients showed brain neural homogeneity dysfunction in the
      visual pathway, which may underline the pathological mechanism of RD patients
      with acute vision loss. Besides, the ReHo values can reflect the progress of the
      RD disease.

PMID- 29200860
TI  - No association between dopamine D3 receptor gene Ser9Gly polymorphism (rs6280)
      and risk of schizophrenia: an updated meta-analysis.
AB  - Objective: Ser9Gly (rs6280) is a functional single-nucleotide polymorphism (SNP)
      in the dopamine receptor D3 (DRD3) gene that may be associated with
      schizophrenia. We performed a meta-analysis to determine whether Ser9Gly
      influences the risk of schizophrenia and examined the relationship between the
      Ser9Gly SNP and the etiology of schizophrenia. Methods: Case-control studies were
      retrieved from literature databases in accordance with established inclusion
      criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to
      evaluate the strength of the association between Ser9Gly and schizophrenia.
      Subgroup analysis and sensitivity analysis were also performed. Results: Seventy
      three studies comprising 10,634 patients with schizophrenia (cases) and 11,258
      controls were included in this meta-analysis. Summary results indicated no
      association between Ser9Gly and risk of schizophrenia. In the dominant genetic
      model, the pooled OR using a random effects model was 0.950 (95% CI, 0.847-1.064;
      P=0.374). Conclusion: Results of this meta-analysis suggest that the Ser9Gly SNP
      is not associated with schizophrenia. These data provide possible avenues for
      future case-control studies related to schizophrenia.

PMID- 29200861
TI  - Statin therapy for preventing cardiovascular diseases in patients treated with
      tacrolimus after kidney transplantation.
AB  - Background: Lipid abnormalities are prevalent in tacrolimus-treated patients. The
      aim of the study was to evaluate the preventive effects of statin therapy on
      major adverse cardiovascular events (MACE) in patients treated with tacrolimus
      based immunosuppression after kidney transplantation (KT), and to identify the
      risk factors. Methods: This observational cohort study included adult patients
      who underwent KT and were treated with tacrolimus. Patients who received any
      lipid-lowering agents except statins, or had a history of immunosuppressant use
      before transplantation were excluded. The primary outcome was the adjusted risk
      of the first occurrence of MACE. The secondary outcomes included the risk of
      individual cardiovascular disease (CVD) and changes in cholesterol level.
      Subgroup analyses were performed in the statin-user group according to the dosage
      and/or type of statin. Results: Compared with the control group (n=73), the
      statin-users (n=92) had a significantly reduced risk of MACE (adjusted HR, 0.31;
      95% CI, 0.13-0.74). In the Cox regression analysis, old age, history of CVD, and
      comorbid hypertension were identified as independent factors associated with
      increased MACE. The total cholesterol levels were not significantly different
      between the two groups. Subjects with higher cumulative defined daily dose of
      statins had significantly lower risks of MACE. Conclusion: Statin therapy in
      patients treated with tacrolimus after KT significantly lowered the risk of MACE.
      Long-term statin therapy is clearly indicated in older kidney transplant
      recipients for secondary prevention.

PMID- 29200862
TI  - Association between serum cystatin C and bone mineral density in Korean adults.
AB  - Background: Serum cystatin C has been known as a novel marker of preclinical
      renal dysfunction, and higher cystatin C levels are associated with increased
      risks of hip and nonvertebral fractures. However, there are few reports on the
      association between serum cystatin C and bone mineral density (BMD), especially
      in the Asian population. We evaluated the association between cystatin C levels
      and BMD of the spine and hip in Korean adults. Methods: A cross-sectional study
      was performed in 865 Korean adults (325 men and 540 women) who participated in a
      comprehensive medical examination program and underwent bone densitometry. Renal
      function was assessed by the estimated glomerular filtration rate (eGFR), which
      was calculated using an equation based on creatinine (eGFRcre) and cystatin C
      (eGFRcys). Results: The serum cystatin C level was negatively correlated with
      different types of BMD, including the lowest lumbar, total lumbar, femoral neck,
      and total femur BMD, in women, but not in men. Higher cystatin C levels were
      associated with a higher prevalence of osteoporosis in women (odds ratio [OR],
      3.68; 95% confidence interval [CI], 1.69-8.03; P=0.001), but not in men (OR,
      0.85; 95% CI, 0.30-2.38; P=0.761). However, this association was attenuated in
      the multivariable model adjusted for age, body mass index, serum 25
      hydroxyvitamin D3, and creatinine (OR, 1.01; 95% CI, 0.38-2.71) in women. In
      addition, the eGFRcys showed a stronger positive correlation with BMD than the
      eGFRcre. Conclusion: Our findings suggest that serum cystatin C levels might help
      identify women with osteoporosis who are susceptible to fractures.

PMID- 29200863
TI  - Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude
      population.
AB  - Introduction: Endothelial function at high altitude has been measured only in
      populations that are genetically adapted to chronic hypoxia. The objective of
      this study was to evaluate endothelial dysfunction (ED) in a nongenetically
      adapted high-altitude population of the Andes mountains, in Huancayo, Peru (3,250
      meters above sea level). Methods: Participants included 61 patients: 28 cases and
      33 controls. The cases were subjects with hypertension, diabetes mellitus,
      obesity, or a history of stroke or coronary artery disease. Flow-mediated
      vasodilation (FMD) of the brachial artery was measured in the supine position, at
      noon, after 5 minutes of resting. The brachial artery was identified above the
      elbow. Its basal diameter was measured during diastole, and FMD was tested after
      5 minutes of forearm ischemia. Intima-media complex in the right carotid artery
      was also determined. An increase in the artery's baseline diameter <10% indicated
      a positive test. Endothelium-independent vasodilation was evaluated with
      sublingual nitrate administration. The intima-media complex in the right carotid
      artery was also measured. Results: 100% of diabetics had ED; ED was also found in
      68.8% of obese individuals, 55% of hypertensive patients, and 46.5% of controls.
      Age, height, body mass index, and waist diameter were higher in the cases as
      compared with the controls. A total of 57.9% (n=11) of the cases and 45.2% (n=19)
      of the controls presented ED. Patients without ED had a mean increase in brachial
      artery diameter of 23.16%, while in those with ED it was only 3.84%. Individuals
      with diabetes or hypertension had a greater thickness of the carotid artery
      intima media layer (1.092 versus 0.664 cm) (p=0.037). A positive test for ED was
      associated with a greater basal diameter of the brachial artery (4.66+/-0.62
      versus 4.23+/-0.59 cm) (p=0.02). A total of 7 patients presented paradoxical
      response, developing posthyperemia vasoconstriction. Discussion: The proportion
      of ED was high among controls and among patients with risk factors. Controls
      showed better FMD profiles than subjects studied in Tibet and the Himalayas.

PMID- 29200864
TI  - Efficacy of noninvasive cardiac imaging tests in diagnosis and management of
      stable coronary artery disease.
AB  - The aim of this review was to discuss the current literature regarding the
      utility of noninvasive imaging in diagnosis and management of stable coronary
      artery disease (CAD) including recent data from large randomized trials assessing
      diagnosis and prognosis. Current guidelines recommend revascularization in
      patients with refractory angina and in those with potential prognostic benefit.
      Appropriate risk stratification through noninvasive assessment is important in
      ensuring patients are not exposed to unnecessary invasive coronary angiograms.
      The past 20 years have seen an unprecedented expansion in noninvasive imaging
      modalities for the assessment of stable CAD, with cardiovascular magnetic
      resonance and computed tomography complementing established techniques such as
      myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In
      this review, we examine the current state-of-the-art in noninvasive imaging to
      provide an up-to-date analysis of current investigation and management options.

PMID- 29200865
TI  - Medicines Regulation in Africa: Current State and Opportunities.
AB  - Sound regulatory systems are critical for protecting public health against use of
      medical products which do not meet international standards of quality, safety and
      efficacy. This review provides a summary of the current status of National
      Medicines Regulatory Authorities (NMRAs) in Africa, and various initiatives that
      have been established to improve their performance. All countries in Africa
      (except Sahrawi Republic), have NMRAs but their organizational set-up and
      functionality is variable. Some are located within Ministries of Health and
      others are semi-autonomous. There is progressive improvement in regulatory
      capacity, particularly in quality control and post-marketing surveillance,
      pharmacovigilance and clinical trials oversight. The African Vaccines Regulatory
      Forum, African Medicines Regulatory Harmonization Initiative, Network of Official
      Medicines Control Laboratories and WHO Prequalification Scheme have helped
      countries strengthen their regulatory capacities. The potential establishment of
      the African Medicines Agency (AMA) in 2018 is an opportunity to improve NMRAs'
      capacity in Africa.

PMID- 29200868
TI  - Prognostic and clinicopathological significance of ubiquitin-specific protease 22
      overexpression in cancers: evidence from a meta-analysis.
AB  - Purpose: This meta-analysis study aimed to reveal the prognostic relevance of
      ubiquitin-specific protease 22 (USP22) expression in patients with cancers.
      Methods: PubMed, Embase, and the Cochrane Library electronic databases were
      searched for relevant studies published up to April 2017. The prognostic value of
      USP22 expression was evaluated by hazard ratio with 95% confidence intervals
      (CIs). Relative risk (RR) with 95% CIs assessed the effects of USP22 expression
      on clinicopathological parameters. A total of 16 studies of 2,233 Chinese
      patients were included in the final meta-analysis. Results: A significant
      association was found between USP22 overexpression and survival in patients with
      cancers. The pooled RR indicated that USP22 overexpression was related to
      histological grade, advanced tumor-node-metastasis stage, positive lymph node
      metastasis, and distant metastasis. Conclusion: This meta-analysis demonstrated
      that USP22 could be a novel biomarker for predicting prognosis in patients with
      cancers in the Chinese population.

PMID- 29200867
TI  - The relationship between IGF2BP2 and PPARG polymorphisms and susceptibility to
      esophageal squamous-cell carcinomas in the eastern Chinese Han population.
AB  - The aim of this case-control study was to assess whether PPARG and IGF2BP2
      polymorphisms confer susceptibility to esophageal squamous-cell carcinoma (ESCC).
      A total of 507 patients pathologically confirmed for ESCC and 1,496 age-, sex-,
      and residence-matched healthy individuals were enrolled. The PPARG rs1801282 C>G
      and rs3856806 C>T and IGF2BP2 rs1470579 A>C and rs4402960 G>T polymorphisms were
      selected and genotyped by SNPscan genotyping assays. Multivariable logistic
      analysis suggested that the PPARG rs3856806 C>T polymorphism might increase the
      risk of ESCC. In different stratified analyses, there were significant
      associations between PPARG rs3856806 C>T and risk of ESCC in female, never
      smoking, drinking, and never-drinking subgroups. In addition, we also found that
      PPARG rs1801282 C>G increased ESCC risk in the never-smoking subgroup. There was
      significant difference in Crs1470579Grs4402960Crs1801282Crs3856806-haplotype
      distribution among ESCC cases and control subjects. In conclusion, our findings
      highlight that PPARG rs1801282 C>G and rs3856806 C>T polymorphisms are candidates
      for susceptibility to ESCC in the eastern Chinese Han population. The
      Crs1470579Grs4402960Crs1801282Crs3856806 haplotype is associated with
      susceptibility to ESCC.

PMID- 29200869
TI  - Preoperative prognostic nutritional index and nomogram predicting recurrence-free
      survival in patients with primary non-muscle-invasive bladder cancer without
      carcinoma in situ.
AB  - Background and objectives: Among the cancers of the urogenital system, bladder
      cancer is ranked second both in incidence and mortality, and hence, a more
      accurate estimate of the prognosis for individual patients with non-muscle
      invasive bladder cancer (NMIBC) is urgently needed. Prognostic nutritional index
      (PNI) which is based on serum albumin levels and peripheral lymphocyte count has
      been confirmed to have prognostic value in various cancers. The aim of this study
      was to clarify the prognostic value of PNI in patients with NMIBC. Methods: Data
      of 329 patients with NMIBC were evaluated retrospectively. Recurrence-free
      survival (RFS) was assessed using the Kaplan-Meier method, and the equivalences
      of survival curves were tested by log-rank tests. The univariate and multivariate
      analyses were performed using the Cox proportional hazards regression model.
      Discrimination of the nomogram was measured by the concordance index. A p-value
      of <0.05 was considered statistically significant. Results: In univariate
      analysis, age, tumor focality, tumor size, tumor grade, pathological T stage and
      preoperative PNI were significantly associated with RFS. Multivariate analysis
      identified PNI as an independent predictor of RFS in patients with NMIBC.
      According to these independent predictors, a nomogram for the prediction of
      recurrence was developed. Conclusion: PNI can be regarded as an independent
      prognostic factor for predicting RFS in NMIBC. The nomogram could be useful to
      improve personalized therapy for patients with NMIBC.

PMID- 29200870
TI  - Identification of hub miRNA biomarkers for bladder cancer by weighted gene
      coexpression network analysis.
AB  - Bladder cancer (BC) is a common urinary system tumor with high aggressiveness,
      and it results in relatively high mortality due to a lack of precise and suitable
      biomarkers. In this study, we applied the weighted gene coexpression network
      analysis method to miRNA expression data from BC patients, and screened for
      network modules associated with BC progression. Hub miRNAs were selected,
      followed by functional enrichment analyses of their target genes for the most
      closely related module. These hub miRNAs were found to be involved in several
      functional pathways including pathway in cancer, regulation of actin
      cytoskeleton, PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK)
      signaling pathway, Wnt signaling pathway, proteoglycans in cancer, focal adhesion
      and p53 signaling pathway via regulating target genes. Finally, their prognostic
      significance was tested using analyses of overall survival. A few novel
      prognostic miRNAs were identified based on expression profiles and related
      survival data. In conclusion, several miRNAs that were critical in BC initiation
      and progression have been identified in this study. These miRNAs, which may
      contribute to a comprehensive understanding of the pathogenesis of BC, could
      serve as potential biomarkers for BC prognosis or as new therapeutic targets.

PMID- 29200872
TI  - Lymphocyte-to-monocyte ratio before chemoradiotherapy represents a prognostic
      predictor for locally advanced rectal cancer.
AB  - Research indicates that cancer-triggered inflammation plays a pivotal role in
      carcinogenesis. Here, we aimed to evaluate the correlation of lymphocyte-to
      monocyte ratio (LMR) before neoadjuvant chemoradiotherapy (CRT) with clinical
      outcomes in patients with locally advanced rectal cancer (LARC). We
      retrospectively enrolled 317 consecutive patients with LARC between 2004 and
      2013. The optimal cutoff values of LMR were determined using receiver operating
      curve analysis. Overall survival (OS) and disease-free survival related to the
      LMR were analyzed using the log-rank test and multivariate Cox regression
      methods. We found that a low LMR (<=4.91) was prominently correlated with worse
      prognostic features and a shorter 3-year survival rate of LARC. Moreover,
      multivariate Cox analysis revealed that elevated LMR was an independent factor
      for better OS (hazard ratio 0.538, 95% confidence interval 0.292-0.991, P=0.047).
      In addition, univariate logistic regression analysis showed that the LMR was not
      associated with tumor pathologic regression. In conclusion, LMR is identified as
      a valuable prognostic marker for predicting the OS of LARC patients receiving
      CRT.

PMID- 29200871
TI  - The clinical significance of CXCL5 in non-small cell lung cancer.
AB  - As a CXC-type chemokine, ENA78/CXCL5 is an important attractant for granulocytes
      by binding to its receptor CXCR2. Recent studies proved that CXCL5/CXCR2 axis
      plays an oncogenic role in many human cancers. However, the exact clinical
      significance of CXCL5 in lung cancer has not been well defined. Here, we found
      that the serum protein expression of CXCL5 was significantly increased in non
      small cell lung cancer (NSCLC) compared with that in healthy volunteers.
      Immunohistochemistry staining revealed that CXCL5 protein was higher in various
      lung cancer tissues compared with normal tissues. Moreover, CXCL5 expression
      correlated with histological grade, tumor size, and TNM stage in NSCLC. Elevated
      CXCL5 protein abundance predicted poor overall survival in adenocarcinoma
      patients. Further meta-analysis demonstrated that CXCL5 mRNA expression was also
      positively associated with tumor stage, lymph node metastasis, and worse
      survival. Kaplan-Meier plot analyses indicated high CXCL5 was associated with
      short overall survival and progression-free survival. Together, these results
      indicated that CXCL5 may be a potential biomarker for NSCLC.

PMID- 29200873
TI  - Clinical application of carbon nanoparticles in curative resection for colorectal
      carcinoma.
AB  - Purpose: To explore the potential of carbon nanoparticles (CNs) for the
      intraoperative detection of positive and negative lymph nodes in the treatment of
      colorectal cancer. Patients and methods: The clinical data of 470 patients
      undergoing surgical procedures for colorectal cancer from June 2010 to February
      2013 were analyzed retrospectively. The patients were divided into the CN group
      (183 males and 161 females; mean age, 58.6+/-12.4 years), who were given a CN
      suspension, and the control group (78 males and 48 females; mean age, 59.1+/-12.2
      years), who were not given a CN suspension. The operative time, blood loss,
      number of lymph nodes detected/positive lymph nodes, and prevalence of
      postoperative complications were compared between the two groups. Three years
      after surgery, 444 cases (327 cases in the CN group and 117 cases in the control
      group) were interviewed, with the remaining 26 cases lost to follow-up. With
      regard to tumor, node, metastasis staging, the survival and prevalence of
      recurrence in each group at 3 years were analyzed. Results: The number of
      positive lymph nodes was higher and the prevalence of blood loss was lower in the
      CN group than in the control group (p<0.05). There were no significant
      differences in the operative time, number of lymph nodes detected, or the
      prevalence of postoperative complications, survival, metastasis, or recurrence
      between the two groups at 3 years (p>0.05). Conclusion: The application of CNs is
      convenient for the detection of lymph nodes to reduce blood loss and increase the
      probability of detecting positive lymph nodes accurately and rapidly.

PMID- 29200874
TI  - Simultaneous overexpression of miR-126 and miR-34a induces a superior antitumor
      efficacy in pancreatic adenocarcinoma.
AB  - Background: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due
      to its high degree of malignancy, increasing incidence, high mortality, and
      unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs
      (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on
      PAC, implicating a possible application of miRNA in tumor therapy. However, the
      therapeutic effect of a single miRNA on pancreatic cancer is limited. Methods: We
      simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoembryonic
      antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined
      the antitumor efficacy of the therapeutic system in in vitro and in vivo
      experiments. Results: In vitro cytological experiments found that the expression
      levels of miR-126 and miR-34a were specifically increased in the AdCEAp
      miR126/34a-infected PAC cells, and the antitumor efficacy was enhanced in aspects
      of cancer cell viability, migration, invasion, and apoptosis, by synergistically
      combining the antitumor effects of overexpressed miR-126 and miR-34a and the
      oncolytic effect of viral replication specifically in PAC cells. The expression
      levels of miR-126 target genes (vascular endothelial growth factor-A and SOX2)
      and miR-34a target genes (cyclin D1, E2F1, and Bcl-2) were markedly decreased in
      the PAC cells after being infected with AdCEAp-miR126/34a. Notable suppression of
      the therapeutic system on tumor growth was also proven in established PAC
      xenograft tumor models in nude mice, which demonstrated that the combination of
      miR-126 and miR-34a exerts more effective antitumor outcomes than a single miRNA.
      Conclusion: The therapeutic system co-expressing miR-126 and miR-34a mediated by
      oncolytic adenovirus is a promising system for PAC target therapy.

PMID- 29200875
TI  - RKIP reduction enhances radioresistance by activating the Shh signaling pathway
      in non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) is exceptionally deadly because the tumors
      lack sensitive early-stage diagnostic biomarkers and are resistant to radiation
      and chemotherapy. Here, we investigated the role and mechanism of Raf kinase
      inhibitory protein (RKIP) in NSCLC radioresistance. The clinical data showed that
      the RKIP expression level was generally lower in radioresistant NSCLC tissues
      than in radiosensitive tissues. Reduced RKIP expression was related to NSCLC
      radioresistance and poor prognosis. In vitro experiments showed that RKIP
      knockdown increased radioresistance and metastatic ability in NSCLC cell lines.
      Mechanistically, RKIP reduction activated the Shh signaling pathway by
      derepressing Smoothened (Smo) and initiating glioma-associated oncogene-1 (Gli1)
      mediated transcription in NSCLC. In addition, the inappropriately activated Shh
      Gli1 signaling pathway then enhanced cancer stem cell (CSC) expression in the
      cell lines. The increasing quantity of CSCs in the tumor ultimately promotes the
      radiation resistance of NSCLC. Together, these results suggest that RKIP plays a
      vital role in radiation response and metastasis in NSCLC. RKIP reduction enhances
      radioresistance by activating the Shh signaling pathway and initiating functional
      CSCs. This role makes it a promising therapeutic target for improving the
      efficacy of NSCLC radiation treatment.

PMID- 29200866
TI  - The crossroads of breast cancer progression: insights into the modulation of
      major signaling pathways.
AB  - Cancer is the disease with highest public health impact in developed countries.
      Particularly, breast cancer has the highest incidence in women worldwide and the
      fifth highest mortality in the globe, imposing a significant social and economic
      burden to society. The disease has a complex heterogeneous etiology, being
      associated with several risk factors that range from lifestyle to age and family
      history. Breast cancer is usually classified according to the site of tumor
      occurrence and gene expression profiling. Although mutations in a few key genes,
      such as BRCA1 and BRCA2, are associated with high breast cancer risk, the large
      majority of breast cancer cases are related to mutated genes of low penetrance,
      which are frequently altered in the whole population. Therefore, understanding
      the molecular basis of breast cancer, including the several deregulated genes and
      related pathways linked to this pathology, is essential to ensure advances in
      early tumor detection and prevention. In this review, we outline key cellular
      pathways whose deregulation has been associated with breast cancer, leading to
      alterations in cell proliferation, apoptosis, and the delicate hormonal balance
      of breast tissue cells. Therefore, here we describe some potential breast cancer
      related nodes and signaling concepts linked to the disease, which can be
      positively translated into novel therapeutic approaches and predictive
      biomarkers.

PMID- 29200876
TI  - Effects of insulin analogs and glucagon-like peptide-1 receptor agonists on
      proliferation and cellular energy metabolism in papillary thyroid cancer.
AB  - Purpose: This study was aimed to investigate the expressions of the insulin
      receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like
      peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer
      (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs
      and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells.
      Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell
      lines were detected by immunohistochemistry and western blotting, respectively.
      Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Levels of members of the phosphoinositol-3
      kinase/AKT serine/threonine kinase (Akt) and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (Erk) signaling pathways were
      measured by western blotting. Energy metabolism of PTC cell lines was analyzed
      using a Seahorse Extracellular Flux analyzer. Results: Three receptors could be
      detected in both PTC tissues and PTC cell lines. Expressions of IGF-1R and GLP-1R
      were more obvious in PTC than in normal thyroid cells. Neither insulin, four
      insulin analogs, and two GLP-1R agonists showed significant effects on the
      proliferation of PTC cells, nor did they influence the levels of Akt/p-Akt and
      Erk/p-Erk. None of these antidiabetic agents could change the mitochondrial
      respiration and glycolysis levels in PTC cell lines. Conclusion: Both PTC tissues
      and the PTC cell lines express IR, IGF-1R, and GLP-1R. However, insulin analogs
      and GLP-1R agonists, which are commonly used to treat patients with diabetes, may
      not influence cell proliferation, the phosphoinositol-3 kinase/Akt and mitogen
      activated protein kinase/Erk pathways, or energy metabolism in PTC cells. For
      now, it is not necessary to avoid use of these antidiabetic agents in patients
      with PTC.

PMID- 29200877
TI  - Microtubule-targeting agents can sensitize cancer cells to ionizing radiation by
      an interphase-based mechanism.
AB  - Background: The cytotoxic effects of microtubule-targeting agents (MTAs) are
      often attributed to targeted effects on mitotic cells. In clinical practice, MTAs
      are combined with DNA-damaging agents such as ionizing radiation (IR) with the
      rationale that mitotic cells are highly sensitive to DNA damage. In contrast,
      recent studies suggest that MTAs synergize with IR by interfering with the
      trafficking of DNA damage response (DDR) proteins during interphase. These
      studies, however, have yet to demonstrate the functional consequences of
      interfering with interphase microtubules in the presence of IR. To address this,
      we combined IR with an established MTA, mebendazole (MBZ), to treat glioma cells
      exclusively during interphase. Materials and methods: To test whether MTAs can
      sensitize interphase cells to IR, we treated GL261 and GBM14 glioma cells with
      MBZ during 3-9 hours post IR (when the mitotic index was 0%). Cell viability was
      measured using a WST-1 assay, and radiosensitization was quantified using the
      dose enhancement factor (DEF). The effect of MBZ on the DDR was studied via
      Western blot analysis of H2AX phosphorylation. To examine the effects of MTAs on
      intracellular transport of DDR proteins, Nbs1 and Chk2, cytoplasmic and nuclear
      fractionation studies were conducted following treatment of glioma cells with
      MBZ. Results: Treatment with MBZ sensitized interphase cells to the effects of
      IR, with a maximal DEF of 1.34 in GL261 cells and 1.69 in GBM14 cells. Treatment
      of interphase cells with MBZ led to more sustained gammaH2AX levels post IR,
      indicating a delay in the DDR. Exposure of glioma cells to MBZ resulted in a dose
      dependent sequestration of Chk2 and Nbs1 in the cytoplasm. Conclusion: This study
      demonstrates that MBZ can sensitize cancer cells to IR independently of the
      induction of mitotic arrest. In addition, evidence is provided supporting the
      hypothesis that MTA-induced radiosensitization is mediated by inhibiting DDR
      protein accumulation into the nucleus.

PMID- 29200878
TI  - In vitro activity of colistin mono- and combination therapy against colistin
      resistant Acinetobacter baumannii, mechanism of resistance, and clinical outcomes
      of patients infected with colistin-resistant A. baumannii at a Thai university
      hospital.
AB  - Purpose: Colistin is a drug of last resort for treating multidrug-resistant
      Acinetobacter baumannii infections. Unfortunately, colistin-resistant A.
      baumannii (CoR-AB) has been reported. Here, we examined the in vitro effect of
      mono- and combined antimicrobials against CoR-AB strains and their resistance
      mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients.
      Patients and methods: Seventeen clinical CoR-AB strains were isolated from
      patients at Phramongkutklao hospital, 2011-2015. The mono- and synergistic
      activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin,
      fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration
      (MIC) and fractional inhibitory concentration index. Clonal relationship and
      resistance genes were determined by repetitive extragenic palindromic polymerase
      chain reaction with specific primers. The effect of carbonyl cyanide 3
      chlorophenylhydrazone combined with colistin was used to test efflux pump
      involvement. Patient treatment outcomes were also reported. Results: The most
      prevalent infection in CoR-AB patients was pneumonia (35.3%), and all patients
      were administered colistin combined with another agent. The 30-day mortality was
      70.6%, and the colistin MIC range and MIC50 was 16-512 MUg/mL and 64 MUg/mL,
      respectively. All CoR-AB strains were sensitive to tigecycline. Sporadic isolates
      were susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole. A
      synergistic or additive effect was observed for colistin plus imipenem or
      meropenem (16.7%), sulbactam (66.7%), or tigecycline (66.7%). The CoR-AB isolates
      could be divided into four different clones (A-D) with a high prevalence of group
      B (47.1%). Eight isolates harbored blaOXA23, blaIMP, blaKPC, and blaNDM, and one
      contained blaOXA23, blaIMP, and blaKPC, while the eight remaining isolates
      carried only blaOXA23. The MIC values of all strains were greatly reduced for
      colistin plus carbonyl cyanide 3-chlorophenylhydrazone. Conclusion: CoR-AB
      clinical isolates exhibited very high colistin resistance and a high frequency of
      resistance genes. The mechanism of colistin resistance appears to be mediated via
      an efflux pump. Thus, certain antimicrobials could be used as salvage therapy for
      CoR-AB infection.

PMID- 29200879
TI  - Cost-consequence analysis of sitagliptin versus sulfonylureas as add-on therapy
      for the treatment of diabetic patients in Italy.
AB  - Objective: Diabetes mellitus is a chronic disease related to a significant impact
      in both epidemiologic and economic terms. In Italy, around 3.6 million people are
      affected by diabetes and this number is expected to increase significantly in the
      next few years. As recommended by current national and international guidelines,
      metformin (Met) is prescribed as first-line pharmacological treatment, and many
      pharmacological alternatives are available for patients uncontrolled with Met
      monotherapy. Despite the availability of many innovative oral antidiabetic drugs
      (OADs), such as dipeptidyl peptidase 4 inhibitors (DPP4-i) and its first-in-class
      sitagliptin (SITA), which entered the Italian market in the last 10 years, their
      usage is consistently lower than traditional drugs such as sulfonylureas (SUs).
      In fact, due to higher acquisition costs, the prescription of innovative OADs in
      Italy is restricted to specialist, resulting in a prominent usage of traditional
      OAD that can be prescribed also by general practitioners (GPs). A cost
      consequence analysis (CCA) was performed in order to compare SITA with SU, as
      second-line therapy in add-on to Met, in terms of costs and related clinical
      events over 36 months. Methods: A CCA was conducted on a hypothetical cohort of
      100,000 type 2 diabetes mellitus (T2DM) patients uncontrolled with Met
      monotherapy, from both the Italian National Health Service (INHS) and societal
      perspective. Therefore, both direct (drugs, self-monitoring, hypoglycemia, major
      cardiovascular events [MACEs], and switch to insulin) and indirect costs
      (expressed in terms of productivity losses) were evaluated. Clinical and economic
      data were collected through Italian national tariffs, literature, and experts'
      opinions. Three expert clinicians finally validated data inputs. To assess
      robustness of base case results, a one-way sensitivity analysis (OWSA) and a
      conservative scenario analysis - excluding MACEs - were carried out. Results: In
      the base case analysis, the higher drug costs related to SITA were offset by
      other management costs (ie, lower use of devices for glycemia self-monitoring,
      lower incidence of hypoglycemia and MACE, and delay to insulin switch). As a
      result, the economic evaluation showed that, compared to SU, SITA was cost saving
      from both societal (-?61,217,723) and INHS (-?51,846,442) perspectives over 3
      years as add-on to Met. The base case results were also confirmed by the scenario
      analysis and by the OWSA performed on the key parameters. The adoption of SITA,
      in a cohort of 100,000 diabetes patients, would avoid 26,882 non-severe
      hypoglycemic events, 6,528 severe hypoglycemic events, and 1,562 MACEs.
      Conclusion: This analysis suggests that, compared to SU, SITA could be a
      sustainable and cost-saving alternative for the management of T2DM patients
      uncontrolled with Met monotherapy from both clinical and economic perspectives.

PMID- 29200880
TI  - Estimating the risk of severe hypoglycemic event related to glucose-lowering
      treatment among Italian patients with diabetes: the HYPOTHESIS database.
AB  - The primary objective of this study was to estimate 1) the annual risk of
      undergoing a severe hypoglycemic event in Italian patients with diabetes and 2)
      the risk of hospitalization following such event. From the HYPOTHESIS database,
      powered by 46 emergency departments covering a 12-million-odd population, data
      were extracted of 1,922 hypoglycemic events occurring in patients with diabetes
      in 2011. The mean age was 71.5 (standard deviation 16.8) years, 50.1% were men,
      and blood glucose at the time of the event was 44.2 (26.5) mg/dL. Patients were
      being treated with insulin alone (55%) or in combination with oral hypoglycemic
      agents (OHA, 15%), or with OHA alone, either in monotherapy (14%) or in multiple
      therapy (16%). Comorbidities were recorded in 71.8% of the patients. Based on the
      rates of glucose-lowering drug use in Italian patients with diabetes, the annual
      risk of undergoing a serious hypoglycemic event was estimated at 1.27% for
      subjects treated with insulin alone, the highest (p<0.00001) as compared with
      insulin + OHA (0.41%) or OHA alone, either in monotherapy or in multiple therapy
      (0.1% and 0.17%, respectively). The risk of being hospitalized following the
      hypoglycemic event was the least (27.6%) for subjects treated with insulin alone
      (p<0.0083). Subjects treated with insulin + OHA showed a lower risk (34.2%) as
      compared with that for subjects treated with OHA (p<0.02). Death occurs in 7% of
      hospitalized patients. Older age (p<0.0001) and comorbidities (p<0.0001) were
      risk factors for hypoglycemia-related hospitalization. Treatments with insulin
      alone (p<0.005) or in combination (p<0.049) were negatively associated with
      hospital admission. Severe hypoglycemic events associated with the use of oral
      glucose-lowering agents carry the highest risk of hospital treatment. As such,
      they are also likely to generate higher tangible and intangible costs.

PMID- 29200881
TI  - Do reimbursement recommendation processes used by government drug plans in Canada
      adhere to good governance principles?
AB  - In democratic societies, good governance is the key to assuring the confidence of
      stakeholders and other citizens in how governments and organizations interact
      with and relate to them and how decisions are taken. Although defining good
      governance can be debatable, the United Nations Development Program (UNDP) set of
      principles is commonly used. The reimbursement recommendation processes of the
      Canadian Agency for Drugs and Technologies in Health (CADTH), which carries out
      assessments for all public drug plans outside Quebec, are examined in the light
      of the UNDP governance principles and compared with the National Institute for
      Health and Care Excellence system in England. The adherence of CADTH's processes
      to the principles of accountability, transparency, participatory, equity,
      responsiveness and consensus is poor, especially when compared with the English
      system, due in part to CADTH's lack of genuine independence. CADTH's overriding
      responsibility is toward the governments that "own," fund and manage it, while
      the agency's status as a not-for-profit corporation under federal law protects it
      from standard government forms of accountability. The recent integration of
      CADTH's reimbursement recommendation processes with the provincial public drug
      plans' collective system for price negotiation with pharmaceutical companies
      reinforces CADTH's role as a nonindependent partner in the pursuit of
      governments' cost-containment objectives, which should not be part of its
      function. Canadians need a national organization for evaluating drugs for
      reimbursement in the public interest that fully embraces the principles of good
      governance - one that is publicly accountable, transparent and fair and includes
      all stakeholders throughout its processes.

PMID- 29200882
TI  - Early intervention in the management of pulmonary arterial hypertension: clinical
      and economic outcomes.
AB  - Pulmonary arterial hypertension (PAH) has a high morbidity rate and is fatal if
      left untreated. Increasing evidence supports early intervention, possibly with
      initial combination therapy. PAH-specific pharmaceuticals, however, are expensive
      and may have serious adverse effects, particularly when used in combination. The
      currently dynamic health care economy reinforces the need for a review of early
      intervention from both outcomes and economic perspectives. We aimed to review the
      clinical and economic impact of PAH therapy, particularly examining drug cost,
      hospitalization burden, and health care economics impact, and the effect of early
      intervention on clinical outcomes. We searched PubMed, Scopus, Ovid, and MEDLINE
      databases from 2005 to 2017 for studies comparing drug cost, clinical outcomes,
      and hospitalization burden associated with therapy for PAH. Emerging data
      indicate that early therapy is effective, but drug therapy is expensive,
      particularly with combination therapy. Efficacy studies also generally show
      benefit of combination therapy for patients in World Health Organization
      functional class II, with a consistent decrease in hospitalization.
      Pharmacoeconomic studies are limited but indicate that increased pharmacy costs
      are at least partially offset by decreased health care utilization, particularly
      inpatient care. Modeling also shows a cost benefit with combination therapy at 2
      years. Nonetheless, more rigorously collected health care economic data should be
      incorporated into future drug efficacy trials to provide a clearer understanding
      of the impact and the associated cost benefit of early PAH therapy. Increasing
      evidence in support of early intervention and combination therapy for PAH is
      associated with rising medication costs that are largely offset by reduced
      hospitalization, on the basis of the currently available literature. Nonetheless,
      the studies performed to date have methodologic limitations that highlight the
      need for prospective studies using more robust economic modeling.

PMID- 29200884
TI  - Associations between body mass index and severity of psoriasis.
AB  - Objective: Compared with healthy people, overweight and obesity are more commonly
      found among those suffering from skin conditions such as psoriasis. The present
      study was an attempt to survey the relationship between obesity and intensity of
      psoriasis. Patients and methods: A total of 42 patients with psoriasis who were
      referred to Farshchian Hospital, Hamadan, participated in this cross-sectional
      descriptive-analytical study. Patients were classified into mild, moderate and
      severe based on the intensity of the disease measured by Psoriasis Area and
      Severity Index (PASI). Body mass index (BMI), waist size, age, gender, smoking
      and drinking habits of the participants were measured and compared. Results: A
      total of 15 (35.07%) patients had mild psoriasis, 9 (21.4%) patients had moderate
      psoriasis and 18 (42.9%) patients suffered from severe psoriasis. Mean BMI of
      mild psoriasis patients was 25.86+/-5.93 kg/m2, and this figure for the moderate
      and severe psoriasis patients was 30.85+/-3.77 kg/m2 and 26.96+/-5.68 kg/m2,
      respectively (P=0.096). Mean waist size of the mild psoriasis patients was
      91.54+/-11.49 cm, and for moderate and severe patients, it was 99+/-8.39 cm and
      92.17+/-10.73 cm, respectively (P=0.211). Conclusion: The results of this study
      showed no significant difference between mean value of body mass index, waist
      size, age and gender in mild, moderate and severe groups of the psoriasis
      patients.

PMID- 29200883
TI  - Obesity and brain illness: from cognitive and psychological evidences to obesity
      paradox.
AB  - Recent findings showed that obesity represents an additional risk factor to
      developing brain illness such as cognitive impairments and psychopathological
      disorders. However, some benefits of overweight in the elderly have been
      identified and an "obesity paradox" has been shown. Currently, it is still
      unknown how obesity and brain functioning could be linked, and the process by
      which body fat independently injures cognitive abilities and psychological well
      being remains unclear. To establish the independent role of obesity on cognitive
      abilities and mental health, clarifying the role played by several factors and
      understanding their interaction is essential. In this review, we discuss the
      relationship between obesity and brain illness and underline the role played by
      confounders and other covariates to determine this link.

PMID- 29200885
TI  - Treatment of complex regional pain syndrome using free-flap surgery: a case
      report.
AB  - Complex regional pain syndrome is a chronic progressive illness with sensory,
      autonomic, trophic, and motor abnormalities. Treatment is difficult and
      controversial. We report the results of free-flap and vein wrapping of the
      superficial peroneal nerve surgery to treat complex regional pain syndrome.

PMID- 29200886
TI  - Monitoring and management of hypertension with obesity in adolescents.
AB  - Largely due to the childhood obesity epidemic, there has been an increase in the
      prevalence of hypertension in children and adolescents. Obesity associated
      hypertension is the most common hypertension phenotype among adolescents.
      Approximately 30% of obese adolescents have elevated blood pressure (BP) or
      hypertension. Updated definitions of elevated BP and hypertension in adolescents
      are now similar to definitions of BP status in adults. For adolescents >=13 years
      of age, elevated BP is 120 to 129/<80 mm Hg. Hypertension, stage 1, is >=130 to
      139/80 to 89 mm Hg, and hypertension, stage 2, is >=140/90 mm Hg. BP measurements
      over separate clinic visits are necessary to verify the diagnosis of elevated BP
      or hypertension. Ambulatory BP monitoring, when available, provides confirmatory
      data on BP status. Causal mechanisms for obesity associated hypertension include
      increased sympathetic nervous system activity, increased renal sodium retention
      secondary to insulin resistance/hyperinsulinemia, and obesity mediated
      inflammation. The primary treatment for obesity associated hypertension is weight
      reduction with lifestyle changes in diet and physical activity. Although
      difficult to achieve, even modest weight reduction can be beneficial. The diet
      should be rich in fruits, vegetables, fiber, and low-fat dairy with reduction in
      salt intake. When lifestyle changes are insufficient to achieve BP control,
      pharmacologic therapy is indicated to achieve a goal BP of <130/80 mm Hg or <90th
      percentile, whichever is lower. Regular BP monitoring is necessary for ongoing
      management of obesity associated hypertension in adolescents.

PMID- 29200887
TI  - Efficacy and safety of pemetrexed and nedaplatin followed by pemetrexed
      maintenance therapy in advanced lung adenocarcinoma.
AB  - Objective: To evaluate the efficacy and safety of pemetrexed and nedaplatin
      followed by pemetrexed maintenance therapy in advanced lung adenocarcinoma.
      Methods: A total of 53 advanced lung adenocarcinoma patients hospitalized between
      July 2013 and June 2016 with a performance status <=2 were enrolled in this
      study. All patients received 4-6 cycles of combination chemotherapy comprising
      pemetrexed (500 mg/m2 dL) and nedaplatin (80 mg/m2 dL). Each chemotherapy cycle
      consisted of 21 days. After the efficacy of the combination chemotherapy was
      assessed, patients with stable disease, partial remission, or complete remission
      received pemetrexed maintenance therapy (500 mg/m2 dL) until disease progression
      or intolerable side effects occurred. Each pemetrexed maintenance therapy cycle
      was 28 days. Results: After completion of the pemetrexed and nedaplatin
      combination chemotherapy, 26 (49.1%), 15 (28.3%), and 12 (22.6%) patients
      exhibited partial remission, stable disease, and progressive disease,
      respectively. Complete remission was not achieved in any patient. Therefore, the
      response and disease control percentages were 49.1% and 77.4%, respectively. A
      total of 38 patients were further administered pemetrexed maintenance
      chemotherapy for an average of 9.8 cycles. The median progression-free survival
      and overall survival of the 38 patients receiving the pemetrexed maintenance
      therapy were 9.3 (95% confidence interval: 8.6-10) months and 16.3 (95%
      confidence interval: 14.5-18.2) months, respectively. The major adverse effects
      included bone marrow suppression and gastrointestinal reactions, which were well
      tolerated. Conclusions: Combination chemotherapy based on pemetrexed and
      nedaplatin is effective for the treatment of advanced lung adenocarcinoma with a
      high tolerance by patients. In addition, pemetrexed maintenance therapy of
      advanced lung adenocarcinoma is safe and effective for the treatment of advanced
      lung adenocarcinoma following pemetrexed and nedaplatin combination chemotherapy.

PMID- 29200888
TI  - Prognostic and clinicopathological value of Ki-67/MIB-1 expression in renal cell
      carcinoma: a meta-analysis based on 4579 individuals.
AB  - Background: Previous studies have investigated the prognostic significance of Ki
      67/MIB-1 expression in renal cell carcinoma (RCC), however, the reports are
      controversial and inconsistent. This study aimed to investigate Ki-67/MIB-1
      expression in RCC and its correlation with prognosis and clinicopathological
      features. Methods: We searched relevant studies that reported associations
      between Ki-67/MIB-1 expression and prognosis in RCC from PubMed, Embase, Web of
      Science, and Cochrane Library studies published until April 14, 2017. Hazard
      ratios (HRs) and 95% confidence intervals (CIs) were extracted from eligible
      studies. Fixed and random effects models were used to calculate pooled HRs and
      95% CIs according to heterogeneity. Results: A total of 4579 participants from 23
      eligible studies were included in this analysis. The results showed that Ki
      67/MIB-1 expression was associated with poor overall survival (HR=2.06, 95% CI:
      1.64-2.57) and cancer specific survival (HR=2.01, 95% CI: 1.66-2.44). In
      addition, Ki-67/MIB-1 expression was also correlated with TNM stage (III/IV vs
      I/II: OR=1.92, 95% CI: 1.61-2.28), pathological T stage (pT3/pT4 vs pT1/pT2:
      OR=1.56, 95% CI: 1.21-2.02), distant metastasis (M1 vs M0: OR=1.81, 95% CI: 1.34
      2.43), and Fuhrman grade (III/IV vs I/II: OR=1.94, 95% CI: 1.21-3.10).
      Conclusion: Our study demonstrates that the presence of high Ki-67/MIB-1
      expression and advanced clinicopathological features were correlated with poor
      prognosis in RCC patients.

PMID- 29200889
TI  - Mesenchymal phenotype of circulating tumor cells is associated with distant
      metastasis in breast cancer patients.
AB  - In this study, we investigated the relationship between the epithelial
      mesenchymal transition phenotype of circulating tumor cells (CTCs) and distant
      metastasis in breast cancer patients. We analyzed the expression of epithelial
      (epithelial cell adhesion molecule, cytokeratin [CK]8, CK18 and CK19) and
      mesenchymal (vimentin and TWIST1) markers in CTCs from a large cohort of Chinese
      breast cancer patients (N=1083) using CanpatrolTM CTC assays. We identified CTCs
      in 84.9% (920/1083) of the breast cancer patients enrolled in this study. Among
      these 920 patients, 547 showed epithelial CTCs, 793 showed biphenotypic CTCs and
      516 showed mesenchymal CTCs. Receiver operating characteristic (ROC) curves
      demonstrated circulation of both biphenotypic and mesenchymal CTCs (area under
      ROC curve value: 0.728; sensitivity: 68.7% and specificity: 71.6%) in patients
      was associated with distant metastasis. These findings demonstrate that the
      epithelial-mesenchymal transition phenotype of CTCs is a potential biomarker
      predictive of distant metastasis in breast cancer.

PMID- 29200890
TI  - Comorbidity index in central cancer registries: the value of hospital discharge
      data.
AB  - Background: The presence of comorbid medical conditions can significantly affect
      a cancer patient's treatment options, quality of life, and survival. However,
      these important data are often lacking from population-based cancer registries.
      Leveraging routine linkage to hospital discharge data, a comorbidity score was
      calculated for patients in the California Cancer Registry (CCR) database.
      Methods: California cancer cases diagnosed between 1991 and 2013 were linked to
      statewide hospital discharge data. A Deyo and Romano adapted Charlson Comorbidity
      Index was calculated for each case, and the association of comorbidity score with
      overall survival was assessed with Kaplan-Meier curves and Cox proportional
      hazards models. Using a subset of Medicare-enrolled CCR cases, the index was
      validated against a comorbidity score derived using Surveillance, Epidemiology,
      and End Results (SEER)-Medicare linked data. Results: A comorbidity score was
      calculated for 71% of CCR cases. The majority (60.2%) had no relevant
      comorbidities. Increasing comorbidity score was associated with poorer overall
      survival. In a multivariable model, high comorbidity conferred twice the risk of
      death compared to no comorbidity (hazard ratio 2.33, 95% CI: 2.32-2.34). In the
      subset of patients with a SEER-Medicare-derived score, the sensitivity of the
      hospital discharge-based index for detecting any comorbidity was 76.5. The
      association between overall mortality and comorbidity score was stronger for the
      hospital discharge-based score than for the SEER-Medicare-derived index, and the
      predictive ability of the hospital discharge-based score, as measured by
      Harrell's C index, was also slightly better for the hospital discharge-based
      score (C index 0.62 versus 0.59, P<0.001). Conclusions: Despite some limitations,
      using hospital discharge data to construct a comorbidity index for cancer
      registries is a feasible and valid method to enhance registry data, which can
      provide important clinically relevant information for population-based cancer
      outcomes research.

PMID- 29200891
TI  - Conditioning on future exposure to define study cohorts can induce bias: the case
      of low-dose acetylsalicylic acid and risk of major bleeding.
AB  - Background: A principle of cohort studies is that cohort membership is defined by
      current rather than future exposure information. Pharmacoepidemiologic studies
      using existing databases are vulnerable to violation of this principle. We
      evaluated the impact of using data on future redemption of prescriptions to
      determine cohort membership, motivated by a published example seeking to emulate
      a "per-protocol" association between continuous versus never use of low-dose
      acetylsalicylic acid (ASA) and major bleeding (e.g., cerebral hemorrhage or
      gastrointestinal bleeding). Materials and methods: Danish medical registry data
      from 2004 to 2011 were used to construct two analytic cohorts. In Cohort 1, we
      used information about future redemption of low-dose ASA prescriptions to
      identify cohorts of continuous and never-ASA users. In Cohort 2, we identified
      ASA initiators and non-initiators using only contemporaneous data and censored
      follow-up for changes in use over time. We implemented propensity score-matched
      Poisson regression to evaluate associations between ASA use and major bleeding
      and estimated adjusted incidence rate differences (IRDs) per 1,000 person-years
      and ratios (IRRs) overall and stratified by time since initiation. Results: Among
      >6 million eligible Danish adults, we identified 403,693 low-dose ASA initiators
      (Cohort 2), of whom 189,150 were defined as continuous users (Cohort 1). Overall,
      IRDs and IRRs were similar across cohorts. However, the IRD for major bleeding in
      the first 90 days was substantially larger in Cohort 1 (IRD=25 per 1,000 person
      years) compared with Cohort 2 (IRD=10 per 1,000 person-years). Conclusion: Using
      future medication redemption data to define baseline cohorts violates basic
      epidemiologic principles. Compared with an approach using only contemporaneous
      data to define cohorts, the approach based on future redemption data generated a
      substantially higher short-term association between low-dose ASA use and major
      bleeding on the absolute, but not the relative, scale possibly due to selection
      and immortal time biases.

PMID- 29200892
TI  - Trends and drivers of skilled birth attendant use in Nigeria (1990-2013): policy
      implications for child and maternal health.
AB  - Introduction: While Nigeria accounts for only 2% of the world population, it
      regrettably shares 14% of global maternal death burden. Whether its reported
      increase in antenatal care utilization is accompanied by increased use of skilled
      birth attendants (SBAs) is not known. This study assessed trends in utilization
      of SBAs in Nigeria between 1990 and 2013 and identified its determinants.
      Methods: Data from four consecutive Nigerian Demographic and Health Survey
      reports between 1990 and 2013 were pooled. We used basic descriptive statistics,
      test of association, and logistic regression to assess the prevalence, relative
      change, and determinants of SBA use at 5% significance level. Sample weights were
      applied, and adjustment was made for survey design and sampling errors. Results:
      Nearly half (46.7%) of the respondents were aged 25-34 years, while half (50.3%)
      of the respondents had no formal education. The prevalence of SBA use increased
      only marginally across the years and characteristics studied, from 32.4% in 1990
      to 38.5% in 2013, an insignificant 6% increase. Educated women used SBA more than
      women with no education (92.4% vs 13.1%), and their odds ratio of using SBA were
      thrice that of uneducated women (odds ratio =3.09, 95% confidence interval =2.17
      4.38). Women involved in decisions regarding their use of health facility were
      12% more likely to use SBAs than others who do not. Educational attainment,
      religion, tribe, rural/urban residence, and zone of residence were significant to
      the use of SBA. Conclusion: The use of SBA was very low throughout the study
      period, barely at one third usage with insignificant changes over the studied
      period. Women empowerment, including decision-making power and residence, were
      the strongest determinants of SBA use. To overturn poor child and maternal health
      outcomes in Nigeria through SBA use, efforts should be targeted at educating
      girls, sexual and reproductive health education, and accessible and improved
      health care facility services.

PMID- 29200893
TI  - Epidemiology of ovarian cancers in Zaria, Northern Nigeria: a 10-year study.
AB  - Background: Globally, the absence of a premalignant stage of ovarian cancer and a
      reliable screening tool make early diagnosis difficult. Locally, poverty,
      ignorance, and lack of organized cancer services make prognosis poor. We describe
      the epidemiological features of ovarian cancer seen at Ahmadu Bello University
      Teaching Hospital Zaria, Northern Nigeria, a tertiary referral center, over a 10
      year period in this challenging setting. Methods: All cases of histologically
      diagnosed ovarian cancer between January 1, 2004 and December 31, 2013 were
      included in the study. Case notes were retrieved to collect clinical data
      including age, parity, clinical stage of disease at presentation, and known
      associated factors. Results were analyzed using Epi infoTM. Results: A total of
      78 patients were included in the study. About 4-13 cases were seen every year
      with a tendency to increasing incidence. The patients were aged 8-80 years with
      mean of 37 years. Sixty-two (79.5%) patients were premenopausal while
      postmenopausal women accounted for only seven cases or 9.0%. There were 17 cases
      (22.3%) of aggressive cancers in patients aged <=20 years. A majority of the
      patients, 65 (83.3%), were parous with only nine (11.5%) patients being
      nulliparous. Serous cyst adenocarcinoma accounted for 32 (41%) cases. Granulosa
      cell tumor was the second commonest with 18 cases (23.1%). The mean age of
      occurrence of serous cyst adenocarcinoma was 31 years and for epithelial ovarian
      cancers in general it was 33.5 years. Endometrioid adenocarcinoma was rare with
      only one case in 10 years. Factors like age, parity, and premenopausal status did
      not appear to be protective to the occurrence of malignant ovarian tumor in this
      group. Conclusion: Increasing numbers of patients with ovarian cancer were seen
      over the 10-year period. Young, premenopausal, parous women made up the majority
      of cases. Serous cystadenocarcinoma was the most common histological variant.

PMID- 29200894
TI  - Potential for severe airway obstruction from pediatric retropharyngeal abscess.
AB  - Retropharyngeal abscesses in the pediatric population can cause severe
      respiratory distress. We report a rare case of significant airway obstruction in
      a 14-month-old patient requiring rapid, emergent tracheotomy after attempts at
      endotracheal intubation by an experienced airway surgeon were unsuccessful. The
      patient was diagnosed with streptococcal pharyngitis 9 days prior to presentation
      to our facility and was being treated with amoxicillin. Prompt diagnosis,
      communication, and appropriate multidisciplinary airway management can lead to
      successful outcomes even in these severe cases.

PMID- 29200895
TI  - Physiological and training characteristics of recreational marathon runners.
AB  - Purpose: The aim of this study was to examine the physical and training
      characteristics of recreational marathon runners within finish time bandings (2.5
      3 h, 3-3.5 h, 3.5-4 h, 4-4.5 h and >4.5 h). Materials and methods: A total of 97
      recreational marathon runners (age 42.4 +/- 9.9 years; mass 69.2 +/- 11.3 kg;
      stature 172.8 +/- 9.1 cm), with a marathon finish time of 229.1 +/- 48.7 min, of
      whom n = 34 were female and n = 63 were male, completed an incremental treadmill
      test for the determination of lactate threshold (LT1), lactate turn point (LT2)
      and running economy (RE). Following a 7-min recovery, they completed a test to
      volitional exhaustion starting at LT2 for the assessment of [Formula: see text].
      In addition, all participants completed a questionnaire gathering information on
      their current training regimes exploring weekly distances, training frequencies,
      types of sessions, longest run in a week, with estimations of training speed, and
      load and volume derived from these data. Results: Training frequency was shown to
      be significantly greater for the 2.5-3 h group compared to the 3.5-4 h runners (P
      < 0.001) and >4.5 h group (P = 0.004), while distance per session (km.session-1)
      was significantly greater for the 2.5-3 h group (16.1 +/- 4.2) compared to the
      3.5-4 h group (15.5 +/- 5.2; P = 0.01) and >4.5 h group (10.3 +/- 2.6; P =
      0.001). Race speed correlated with LT1 (r = 0.791), LT2 (r = 0.721) and distance
      per session (r = 0.563). Conclusion: The data highlight profound differences for
      key components of marathon running ([Formula: see text], LT1, LT2, RE and %
      [Formula: see text]) within a group of recreational runners with the
      discriminating training variables being training frequency and the absolute
      training speed.

PMID- 29200896
TI  - Methamphetamine Use With Subsequent Thyrotoxicosis/Thyroid Storm,
      Agranulocytosis, and Modified Total Thyroidectomy: A Case Report.
AB  - Thyroid storm is a rare, potentially lethal condition involving collapse of the
      hypothalamic-pituitary-thyroid feedback loop. Thyroid storm carries a significant
      mortality rate, thus requiring prompt identification and treatment. A 47-year-old
      woman presented to the emergency department complaining of palpitations,
      shortness of breath, and emesis for 24 hours after using methamphetamine. Past
      medical history was significant for untreated hyperthyroidism. Physical
      examination revealed a prominent, palpable thyroid. The Burch-Wartofsky-Score was
      35. Management for thyroid storm included propylthiouracil (PTU), super saturated
      potassium iodide, intravenous hydrocortisone, and propranolol. However, a rare
      drug reaction to PTU on day 3 resulted in agranulocytosis. Propylthiouracil was
      withheld and a modified total thyroidectomy performed on day 8 without
      complications and the patient discharged on day 10 with levothyroxine.
      Undertreated hyperthyroidism may predispose patients to catecholamine-induced
      thyrotoxicosis due to catecholamine hypersensitivity. With known methamphetamine
      use, methamphetamine toxicity and a methamphetamine-exacerbated thyroid storm
      need to be included in the differential diagnosis in a patient presenting with
      signs of thyrotoxicosis. In addition, treating patients with agranulocytosis from
      PTU with a modified total thyroidectomy using ligation of the vascular supply as
      the initial surgical step limits release of thyroid hormone into the blood stream
      during thyroidectomy and decreases the possibility of intra operative thyroid
      storm.

PMID- 29200897
TI  - Insulinoma and Chronic Kidney Disease: An Uncommon Conundrum Not to Be
      Overlooked.
AB  - A hypertensive man with chronic kidney disease (CKD) secondary to polycystic
      disease was hospitalized for symptoms related to hypoglycemia. Fasting test
      elicited symptomatic hypoglycemia after 12 hours, which was associated with
      inappropriately unsuppressed normal insulin and C-peptide levels. Neither
      ultrasonography (US) nor magnetic resonance imaging detected any pancreatic
      tumor. Endoscopic ultrasonography (EUS) showed a small isoechogenic nodule
      suspect for neuroendocrine tumor in the pancreatic head. 68Gallium-DOTA-Tyr3
      octreotide positron emission tomography/computed tomography revealed intense
      uptake by a small region in the pancreatic head. Surgical exploration together
      with intraoperative US confirmed the nodule in the pancreatic head and evidenced
      another hypoechogenic one in the uncinate process. Both nodules were enucleated,
      but only the latter, which had not been previously detected by EUS, proved
      compatible with insulinoma on combined histology and immunohistochemistry. After
      nodule enucleation, hypoglycemia resolved and did not relapse. Insulinoma, as a
      major cause of unexplained hypoglycemia, requires careful hormonal and
      instrumental workup. In patients with CKD, the interpretation of biochemical
      criteria for the diagnosis of insulinoma can be challenging. Localization
      techniques may display pitfalls. Surgery is curative in most patients but long
      term follow-up is required.

PMID- 29200898
TI  - Circulating Clusterin and Osteopontin Levels in Asthma and Asthmatic Pregnancy.
AB  - Asthma in pregnancy poses a risk of adverse outcomes. Osteopontin and clusterin
      emerged as asthma biomarkers; however, their circulating levels during pregnancy
      are unknown yet. This cross-sectional study investigated peripheral osteopontin
      and clusterin levels and their relationship to disease control in 26 asthmatic
      pregnant (AP), 22 asthmatic nonpregnant (ANP), and 25 healthy pregnant (HP) women
      and 12 healthy controls (HNP). Osteopontin levels of ANP and HNP were similar
      (2.142 [1.483-2.701] versus 2.075 [1.680-2.331] ng/mL, p = 0.7331). Pregnancy
      caused a marked elevation in both healthy (HP: 3.037 [2.439-4.015] ng/ml, p =
      0.003 versus HNP) and asthmatic (AP: 2.693 [1.581-3.620] ng/ml) patients; thus
      the pregnant groups did not differ (p = 0.3541). Circulating clusterin levels
      were comparable in ANP and HNP (109.2 [95.59-116.3] versus 108.8 [97.94-115.3]
      ug/mL, p = 0.8730) and the level was lower in HP (98.80 [84.26-105.5] ug/mL, p =
      0.0344 versus HNP). In contrast, the level was higher in AP (111.7 [98.84-125.6]
      ug/mL, p = 0.0091 versus HP). In ANP, a positive correlation of PEF (r = 0.3405;
      p = 0.0221) and a negative correlation of Raw (r = -0.3723; p = 0.0128) to
      clusterin level were detected. Circulating osteopontin level increases in
      pregnancy regardless of concomitant well-controlled asthma, indicating its
      gestational role. Clusterin level decreases in healthy but not in asthmatic
      pregnancy and correlates directly with lung function.

PMID- 29200899
TI  - Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal
      muscle.
AB  - Obesity is known to induce inhibition of glucose uptake, reduction of lipid
      metabolism, and progressive loss of skeletal muscle function, which are all
      associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are
      dynamic organelles that regulate cellular metabolism and bioenergetics, including
      ATP production via oxidative phosphorylation. Due to these critical roles of
      mitochondria, mitochondrial dysfunction results in various diseases such as
      obesity and type 2 diabetes. Obesity is associated with impairment of
      mitochondrial function (e.g., decrease in O2 respiration and increase in
      oxidative stress) in skeletal muscle. The balance between mitochondrial fusion
      and fission is critical to maintain mitochondrial homeostasis in skeletal muscle.
      Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion
      and fission by favorably shifting fission or reducing fusion proteins. Mitophagy
      is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces
      mitochondrial biogenesis in skeletal muscle and increases accumulation of
      dysfunctional cellular organelles, suggesting that mitophagy does not work
      properly in obesity. Mitochondrial dysfunction and oxidative stress are reported
      to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in
      skeletal muscle. It is well known that exercise is the most effective
      intervention to protect against obesity. Although the cellular and molecular
      mechanisms by which exercise protects against obesity-induced mitochondrial
      dysfunction in skeletal muscle are not clearly elucidated, exercise training
      attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance
      between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in
      obese skeletal muscle.

PMID- 29200900
TI  - Genistein attenuates isoflurane-induced neurotoxicity and improves impaired
      spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt
      signaling.
AB  - Anesthetics are used extensively in surgeries and related procedures to prevent
      pain. However, there is some concern regarding neuronal degeneration and
      cognitive deficits arising from regular anesthetic exposure. Recent studies have
      indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response
      element-binding protein (CREB) are involved in learning and memory processes.
      Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective
      effects. The present study was performed to examine the protective effect of
      genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were
      exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups
      of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg
      body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7.
      Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining
      following isoflurane exposure. Genistein significantly reduced apoptosis in the
      hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and
      cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR
      analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively
      upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to
      activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also
      significantly activated. Genistein administration improved general behavior and
      enhanced learning and memory in the rats. These observations suggest that
      genistein exerts neuroprotective effects by suppressing isoflurane-induced
      neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

PMID- 29200901
TI  - The bifunctional effect of propofol on thromboxane agonist (U46619)-induced
      vasoconstriction in isolated human pulmonary artery.
AB  - Propofol is known to cause vasorelaxation of several systemic vascular beds.
      However, its effect on the pulmonary vasculature remains controversial. In the
      present study, we investigated the effects of propofol on human pulmonary
      arteries obtained from patients who had undergone surgery. Arterial rings were
      mounted in a Multi-Myograph system for measurement of isometric forces. U46619
      was used to induce sustained contraction of the intrapulmonary arteries, and
      propofol was then applied (in increments from 10-300 uM). Arteries denuded of
      endothelium, preincubated or not with indomethacin, were used to investigate the
      effects of propofol on isolated arteries. Propofol exhibited a bifunctional
      effect on isolated human pulmonary arteries contracted by U46619, evoking
      constriction at low concentrations (10-100 uM) followed by secondary relaxation
      (at 100-300 uM). The extent of constriction induced by propofol was higher in an
      endothelium-denuded group than in an endothelium-intact group. Preincubation with
      indomethacin abolished constriction and potentiated relaxation. The maximal
      relaxation was greater in the endothelium-intact than the endothelium-denuded
      group. Propofol also suppressed CaCl2-induced constriction in the 60 mM K+
      containing Ca2+-free solution in a dose-dependent manner. Fluorescent imaging of
      Ca2+ using fluo-4 showed that a 10 min incubation with propofol (10-300 uM)
      inhibited the Ca2+ influx into human pulmonary arterial smooth muscle cells
      induced by a 60 mM K+-containing Ca2+-free solution. In conclusion, propofol
      induced arterial constriction appears to involve prostaglandin production by
      cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends
      in part on endothelial function, principally on the inhibition of calcium influx
      through L-type voltage-operated calcium channels.

PMID- 29200902
TI  - JPH203, a selective L-type amino acid transporter 1 inhibitor, induces
      mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells.
AB  - Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type
      amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and
      presumed to support their increased growth and proliferation. This study examined
      the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its
      mechanism for cell death in Saos2 human osteosarcoma cells. FOB human
      osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their
      associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2
      cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid
      transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As
      expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far
      more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH
      inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard.
      Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2
      cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling
      pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the
      active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl
      2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via
      JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis
      mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by
      inducing the intracellular depletion of neutral amino acids essential for cell
      growth in Saos2 human osteosarcoma cells.

PMID- 29200903
TI  - Ardipusilloside-I stimulates gastrointestinal motility and phosphorylation of
      smooth muscle myosin by myosin light chain kinase.
AB  - Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from
      Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of
      ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The
      experiment of smooth muscle contraction directly monitored the contractions of
      the isolated jejunal segment (IJS) in different contractile states, and the
      effects of ardipusilloside-I on myosin were measured in the presence of Ca2+
      calmodulin using the activities of 20 kDa myosin light chain (MLC20)
      phosphorylation and myosin Mg2+-ATPase. The effects of ardipusilloside-I on
      gastro emptying and intestinal transit in constipation-predominant rats were
      observed, and the MLCK expression in jejuna of constipated rats was determined by
      western blot. The results showed that, ardipusilloside-I increased the
      contractility of IJS in a dose-dependent manner and reversed the low contractile
      state (LCS) of IJS induced by low Ca2+, adrenaline, and atropine respectively.
      There were synergistic effects on contractivity of IJS between ardipusilloside-I
      and ACh, high Ca2+, and histamine, respectively. Ardipusilloside-I could
      stimulate the phosphorylation of MLC20 and Mg2+-ATPase activities of Ca2+-
      dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric
      emptying and intestinal transit in normal and constipated rats in vivo,
      respectively, and increased the MLCK expression in the jejuna of constipation
      predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could
      effectively excite gastrointestinal motility in vitro and in vivo.

PMID- 29200904
TI  - Taurine relaxes human radial artery through potassium channel opening action.
AB  - The vascular actions and mechanisms of taurine were investigated in the isolated
      human radial artery (RA). RA rings were suspended in isolated organ baths and
      tension was recorded isometrically. First, a precontraction was achieved by
      adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT,
      30 uM) to organ baths. When the precontractions were stable, taurine (20, 40, 80
      mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride
      (10 uM to 10 mM)-induced contractions was investigated. Taurine-induced
      relaxations were also tested in the presence of the K+ channel inhibitors
      tetraethylammonium (1 mM), glibenclamide (10 uM) and 4-aminopyridine (1 mM).
      Taurine did not affect the basal tone but inhibited the contraction induced by 5
      HT and KCl. Calcium chloride-induced contractions were significantly inhibited in
      the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was
      inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4
      aminopyridine did not affect taurine-induced relaxations. Present experiments
      show that taurine inhibits 5-HT and KCl-induced contractions in RA, and suggest
      that large conductance Ca2+-activated K+ channels may be involved in taurine
      induced relaxation of RA.

PMID- 29200905
TI  - MPTP-induced vulnerability of dopamine neurons in A53T alpha-synuclein
      overexpressed mice with the potential involvement of DJ-1 downregulation.
AB  - Familial Parkinson's disease (PD) has been linked to point mutations and
      duplication of the alpha-synuclein (alpha-syn) gene. Mutant alpha-syn expression
      increases the vulnerability of neurons to exogenous insults. In this study, we
      developed a new PD model in the transgenic mice expressing mutant hemizygous
      (hemi) or homozygous (homo) A53T alpha-synuclein (alpha-syn Tg) and their
      wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for
      5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were
      reduced in the alpha-syn Tg but not WT mice by sub-toxic MPTP injection. In the
      adhesive removal test, time to remove paper was significantly increased only in
      the homo alpha-syn Tg mice. In the challenging beam test, the hemi and homo alpha
      syn Tg mice spent significantly longer time to traverse as compared to that of WT
      group. In order to find out responsible proteins related with vulnerability of
      mutant alpha-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were
      examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were
      significantly decreased in the alpha-syn Tg mice. Moreover, A53T alpha-syn
      overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest
      that the vulnerability to oxidative injury such as MPTP of A53T alpha-syn mice
      can be explained by downregulation of DJ-1.

PMID- 29200906
TI  - Effects of intermittent ladder-climbing exercise training on mitochondrial
      biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle
      aged rats.
AB  - The aim of this study is to investigate the effects of intermittent ladder
      climbing exercise training on mitochondrial biogenesis and ER stress of the
      cardiac muscle in high fat diet-induced obese middle-aged rats. We induced
      obesity over 6 weeks of period in 40 male Sprague-Dawley rats around 50 weeks
      old, and were randomly divided into four experimental groups: chow, HFD,
      exercise+HFD, and exercise+chow. The exercising groups underwent high-intensity
      intermittent training using a ladder-climbing and weight exercise 3 days/week for
      a total of 8 weeks. High-fat diet and concurrent exercise resulted in no
      significant reduction in body weight but caused a significant reduction in
      visceral fat weight (p<0.05). Expression of PPARdelta increased in the exercise
      groups and was significantly increased in the high-fat diet+exercise group
      (p<0.05). Among the ER stress-related proteins, the expression levels of p-PERK
      and CHOP, related to cardiac muscle damage, were significantly higher in the
      cardiac muscle of the high-fat diet group (p<0.05), and were significantly
      reduced by intermittent ladder-climbing exercise training (p<0.05). Specifically,
      this reduction was greater when the rats underwent exercise after switching back
      to the chow diet with a reduced caloric intake. Collectively, these results
      suggest that the combination of intermittent ladder-climbing exercise training
      and a reduced caloric intake can decrease the levels of ER stress-related
      proteins that contribute to cardiac muscle damage in obesity and aging. However,
      additional validation is required to understand the effects of these changes on
      mitochondrial biogenesis during exercise.

PMID- 29200907
TI  - Chronic cerebral hypoperfusion and plasticity of the posterior cerebral artery
      following permanent bilateral common carotid artery occlusion.
AB  - Vascular dementia (VaD) is a group of heterogeneous diseases with the common
      feature of cerebral hypoperfusion. To identify key factors contributing to VaD
      pathophysiology, we performed a detailed comparison of Wistar and Sprague-Dawley
      (SD) rats subjected to permanent bilateral common carotid artery occlusion
      (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a
      reference memory test using a five-radial arm maze with tactile cues. Continuous
      monitoring of cerebral blood flow (CBF) was performed with a laser Doppler
      perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for
      evaluation of the brain vasculature and white matter damage after BCCAo. We found
      reference memory impairment in Wistar rats, but not in SD rats. Moreover, our
      LDPI system revealed that Wistar rats had significant hypoperfusion in the brain
      region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats
      showed more profound CBF reduction in the forebrain region than did SD rats. Post
      mortem analysis of brain vasculature demonstrated greater PCA plasticity at all
      time points after BCCAo in Wistar rats. Finally, we confirmed white matter
      rarefaction that was only observed in Wistar rats. Our studies show a
      comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to
      severe PCA dolichoectasia, which correlated well with white matter lesion and
      memory decline.

PMID- 29200908
TI  - Ursolic acid supplementation decreases markers of skeletal muscle damage during
      resistance training in resistance-trained men: a pilot study.
AB  - Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle
      function in resistance-trained men. This study aimed to determine, using the same
      experimental paradigm, whether UA also has beneficial effects on exercise-induced
      skeletal muscle damage markers including the levels of cortisol, B-type
      natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase
      myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained
      men. Sixteen healthy participants were randomly assigned to resistance training
      (RT) or RT+UA groups (n=8 per group). Participants were trained according to the
      RT program (60~80% of 1 repetition, 6 times/week), and the UA group was
      additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples
      were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK
      MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no
      significant change in body composition and markers of skeletal muscle damage,
      whereas RT+UA group showed slightly decreased body weight and body fat percentage
      and slightly increased lean body mass, but without statistical significance. In
      addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH
      levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal
      muscle damage markers after RT. This finding provides evidence for a potential
      new therapy for resistance-trained men.

PMID- 29200909
TI  - The efficacy of combination treatment of gabapentin and electro-acupuncture on
      paclitaxel-induced neuropathic pain.
AB  - Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy.
      Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its
      effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors.
      Electro-acupuncture (EA) is used for treating various types of pain via its
      action through spinal opioidergic and noradrenergic receptors. Here, we
      investigated whether combined treatment of these two agents could exert a
      synergistic effect on paclitaxel-induced cold and mechanical allodynia, which
      were assessed by the acetone drop test and von Frey filament assay, respectively.
      Significant signs of allodynia were observed after four paclitaxel injections (a
      cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36,
      Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and
      highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but
      they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest
      dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief
      analgesic effect. The combination of the lowest dose of GBT and EA resulted in a
      greater and longer effect, without inducing motor dysfunction. This effect on
      mechanical allodynia was blocked by spinal opioidergic (naloxone, 20 MUg), or
      noradrenergic (idazoxan, 10 MUg) receptor antagonist, whereas on cold allodynia,
      only opioidergic receptor antagonist blocked the effect. In conclusion, the
      combination of the lowest dose of GBT and EA has a robust and enduring analgesic
      action against paclitaxel-induced neuropathic pain, and it should be considered
      as an alternative treatment method.

PMID- 29200910
TI  - Comparative effects of angiotensin II and angiotensin-(4-8) on blood pressure and
      ANP secretion in rats.
AB  - Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and
      from C-terminal by Ang converting enzyme (ACE) to generate several truncated
      angiotensin peptides (Angs). The truncated Angs have different biological effects
      but it remains unknown whether Ang-(4-8) is an active peptide. The present study
      was to investigate the effects of Ang-(4-8) on hemodynamics and atrial
      natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial
      stretch caused increases in atrial contractility by 60% and in ANP secretion by
      70%. Ang-(4-8) (0.01, 0.1, and 1 uM) suppressed high stretch-induced ANP
      secretion in a dose-dependent manner. Ang-(4-8) (0.1 uM)-induced suppression of
      ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1
      receptor (AT1R) but not by an antagonist of AT2R or AT4R. Ang-(4-8)-induced
      suppression of ANP secretion was attenuated by the pretreatment with inhibitor of
      phospholipase (PLC), inositol triphosphate (IP3) receptor, or nonspecific protein
      kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to
      Ang II. However, Ang-(4-8) 10 uM caused an increased mean arterial pressure which
      was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8)
      suppresses high stretch-induced ANP secretion through the AT1R and PLC/IP3/PKC
      pathway. Ang-(4-8) is a biologically active peptide which functions as an
      inhibition mechanism of ANP secretion and an increment of blood pressure.

PMID- 29200911
TI  - Dual control of the vestibulosympathetic reflex following hypotension in rats.
AB  - Orthostatic hypotension (OH) is associated with symptoms including headache,
      dizziness, and syncope. The incidence of OH increases with age. Attenuation of
      the vestibulosympathetic reflex (VSR) is also associated with an increased
      incidence of OH. In order to understand the pathophysiology of OH, we
      investigated the physiological characteristics of the VSR in the disorder. We
      applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation
      in order to induce hypotension. Expression of pERK in the intermediolateral cell
      column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and
      blood pressure were evaluated following the administration of glutamate and/or
      SNP. SNP-induced hypotension led to increased pERK expression in the medial
      vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the
      IMC, as well as increased blood epinephrine levels. We co-administered either a
      glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the
      RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the
      MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC,
      and increased blood epinephrine levels. Administration of the glutamate receptor
      antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK
      expression and blood epinephrine levels caused by SNP-induced hypotension. These
      results suggest that two components of the pathway which maintains blood pressure
      are involved in the VSR induced by SNP. These are the neurogenic control of blood
      pressure via the RVLM and the humoral control of blood pressure via epinephrine
      release from the adrenal medulla.

PMID- 29200912
TI  - Biphasic augmentation of alpha-adrenergic contraction by plumbagin in rat
      systemic arteries.
AB  - Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits
      anticancer, antibacterial, and antifungal activities via modulating various
      signaling molecules. However, its effects on vascular functions are rarely
      studied except in pulmonary and coronary arteries where NADPH oxidase (NOX)
      inhibition was suggested as a mechanism. Here we investigate the effects of
      plumbagin on the contractility of skeletal artery (deep femoral artery, DFA),
      mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone
      had no effect on the isometric tone of DFA, 1 uM phenylephrine (PhE)-induced
      partial contraction was largely augmented by plumbagin (DeltaTPlum, 125% of 80 mM
      KCl-induced contraction at 1 uM). With relatively higher concentrations (>5 uM),
      plumbagin induced a transient contraction followed by tonic relaxation of DFA.
      Similar biphasic augmentation of the PhE-induced contraction was observed in MA
      and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor
      inhibited DeltaTPlum in DFA. Also, pretreatment with tiron or catalase did not
      affect DeltaTPlum of DFA. Under the inhibition of PhE-contraction with L-type
      Ca2+ channel blocker (nifedipine, 1 uM), plumbagin still induced tonic
      contraction, suggesting Ca2+-sensitization mechanism of smooth muscle. Although
      DeltaTPlum was consistently observed under pretreatment with Rho A-kinase
      inhibitor (Y27632, 1 uM), a PKC inhibitor (GF 109203X, 10 uM) largely suppressed
      DeltaTPlum. Taken together, it is suggested that plumbagin facilitates the PKC
      activation in the presence of vasoactive agonists in skeletal arteries. The
      biphasic contractile effects on the systemic arteries should be considered in the
      pharmacological studies of plumbagin and 1,4-naphthoquinones.

PMID- 29200913
TI  - Developmental changes in GABAA tonic inhibition are compromised by multiple
      mechanisms in preadolescent dentate gyrus granule cells.
AB  - The sustained tonic currents (Itonic) generated by gamma-aminobutyric acid A
      receptors (GABAARs) are implicated in diverse age-dependent brain functions.
      While various mechanisms regulating Itonic in the hippocampus are known, their
      combined role in Itonic regulation is not well understood in different age
      groups. In this study, we demonstrated that a developmental increase in GABA
      transporter (GAT) expression, combined with gradual decrease in GABAAR alpha5
      subunit, resulted in various Itonic in the dentate gyrus granule cells (DGGCs) of
      preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at
      infantile (P6-8 and P13-15) and juvenile (P20-22 and P27-29) stages, with
      stabilization observed thereafter in adolescents (P34-36) and young adults (P41
      43). Itonic facilitation of a selective GAT-1 blocker (NO-711) was significantly
      less at P6-8 than after P13-15. The facilitation of Itonic by SNAP-5114, a GAT-3
      inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In
      contrast, Itonic in the presence of a nonselective GAT blocker (nipecotic acid,
      NPA) gradually decreased with age during the preadolescent period, which was
      mimicked by Itonic changes in the presence of exogenous GABA. Itonic sensitivity
      to L-655,708, a GABAAR alpha5 subunit inverse agonist, gradually decreased during
      the preadolescent period in the presence of NPA or exogenous GABA. Finally,
      Western blot analysis showed that the expression of the GABAAR alpha5 subunit in
      the dentate gyrus gradually decreased with age. Collectively, our results
      suggested that the Itonic regulation of altered GATs is under the final tune of
      GABAAR alpha5 subunit activation in DGGCs at different ages.

PMID- 29200914
TI  - A new species of Hyalella from the High Andes of Ecuador (Crustacea, Amphipoda,
      Hyalellidae).
AB  - Hyalella cajasisp. n. is described from high altitude shallow water lakes in
      southern Ecuador. This is the second representative of the genus recorded in the
      country after H. meinerti. The new species shares with nine South American
      species of the genus the display of a smooth, non-processiferous body, a male
      first uropod with a modified curved robust seta on the endopod, and six pairs of
      sternal gills. The new taxon can be distinguished from these species based on the
      presence/absence of eyes; relative length of antenna 1 with respect to antenna 2;
      presence/absence of short pointed robust seta distally on palp of maxilla 1;
      number of pappose setae proximally on medial margin of inner lobe of maxilla 2;
      elongation and curvature of the modified robust seta of endopod of male uropod 1;
      relative length of ramus of uropod 3 with respect to protopod; and armature and
      outline of telson, among other features. It seems to be a high-altitude endemic
      to the Cajas Massif in Azuay Province, being replaced in the same area at lower
      altitudes by H. meinerti.

PMID- 29200915
TI  - Updated catalogue and taxonomic notes on the Old-World scorpion genus Buthus
      Leach, 1815 (Scorpiones, Buthidae).
AB  - Since the publication of the ground-breaking "Catalogue of the scorpions of the
      world (1758-1998)" (Fet et al. 2000) the number of species in the scorpion genus
      Buthus Leach, 1815 has increased 10-fold, and this genus is now the fourth
      largest within the Buthidae, with 52 valid named species. Here we revise and
      update the available information regarding Buthus. A new combination is proposed:
      Buthus halius (C. L. Koch, 1839), comb. n. from Portugal and Spain. B. halius is
      removed from junior synonymy with Buthus occitanus (Amoreux, 1789), and proposed
      as a senior synonym of B. ibericus Lourenco & Vachon, 2004, syn. n. Moreover,
      following I.C.Z.N. article 23.9.2 we propose to maintain as valid B.
      ibericus(nomen protectum) and to consider the disued B. halius as a nomen oblitum
      . Buthus europaeus tridentatus Franganillo, 1918 is proposed as a junior synonym
      of B. occitanus (Amoreux, 1789), syn. n.Buthus sabulicola Touloun, 2012 is
      proposed as a junior synonym of Buthus bonito Lourenco & Geniez, 2005, syn.
      n.Buthus occitanus tunetanus neeli Gysin, 1969 is proposed as an informal senior
      synonym of Buthus tassili Lourenco, 2002, informal syn. n. Two taxa are rised to
      species rank, Buthus nigrovesiculosus Hirst, 1925, stat. n. and Buthus parroti
      Vachon, 1949, stat. n.. We further confirm the restricted distribution of B.
      occitanus that is confined to southeastern France and northwestern Iberian
      Peninsula and does not occur in North Africa. Additionally, Androctonus barbouri
      (Werner, 1932), comb. n. from the Agadir region of Morocco, is hereby transferred
      to the genus Androctonus. We summarize and provide a critical appraisal of the
      diagnostic characters currently in use for the genus. The catalogue section
      considers the names for species, subspecies and varieties that have been used for
      Buthus scorpions. Information about types, including collection numbers and
      localities are included when available. Finally, an annotated listing of
      synonymies and an updated bibliography are given.

PMID- 29200916
TI  - Study on Tullbergiidae of Tibet, China I. Metaphorura, Mesaphorura and Prabhergia
      (Hexapoda, Collembola).
AB  - The Tullbergiidae of Tibet is studied for the first time and the genus
      Metaphorura Bagnall, 1936 is firstly recorded in China. Metaphorura motuoensissp.
      n. from southeastern Tibet is described and illustrated. It is characterized by
      the presence of 1+1 pseudocelli on thoracic segment I, few vesicles (14 -16) on
      PAO, pseudocellar formula as 11/111/11111, all pseudocelli of type II, setae p4
      on abdominal segment V as microsetae, weakly differentiated sensory seta p3 on
      abdominal segment V, absence of median process on Abd VI. In addition,
      Mesaphorura yosii (Rusek, 1967), Mesaphorura hylophila Rusek, 1982, and
      Prabhergia imadatei Tamura & Zhao, 1996 are recorded in Tibet for the first time.
      The type specimens of P. imadatei are re-examined and errors in the original
      description of chaetotaxy are corrected.

PMID- 29200917
TI  - First report of the leaf-mining genus Antispila Hubner, [1825] from mainland
      China, with the description of a new species feeding on Cornus (Lepidoptera,
      Heliozelidae).
AB  - The genus Antispila Hubner, [1825] is newly recorded from mainland China.
      Antispila sinensissp. n., the first formally named Heliozelidae species in
      mainland China, is described. The host plant of the new species, Cornus walteri
      Wangerin (Cornaceae), is widespread through east Asia and is used as a shade tree
      in city parks in Jinan City, where the moth causes damage to foliage.
      Morphological and molecular analyses distinguish A. sinensissp. n. from its close
      relatives. The adult, pupa, larva, host plant, leaf-mines, and the shield of the
      new species are illustrated, as are male and female genitalia, venation, and
      larval chaetotaxy. DNA barcodes of the new species are also provided.

PMID- 29200918
TI  - A new subspecies of sea snake, Hydrophis platurus xanthos, from Golfo Dulce,
      Costa Rica.
AB  - We describe a distinctive new subspecies of sea snake from the occasionally
      anoxic inner-basin waters of Golfo Dulce, Costa Rica, based on combined data
      garnered between 2010 and 2017 for 154 specimens, 123 free-ranging and 31 museum
      held. The yellow sea snake, Hydrophis platurus xanthos Bessesen & Galbreath,
      subsp. n., is diagnosed by a notably smaller body size and nearly uniform yellow
      coloration, which contrasts with the black and yellow striae and tail spots or
      bands typical of the species. Within the modest geographic range (circa 320 km2),
      nearly all specimens possess both diagnostic character states. Bathymetrics
      appear to restrict genetic flow between this allopatric population and
      conspecifics in the broader Eastern Pacific. In perspicuous contrast to typical
      H. platurus, H. p. xanthos shows no association with drift lines, and feeds at
      night in turbulent waters, assuming a sinusoidal ambush posture never previously
      reported for the species. This evolutionarily significant unit (ESU) warrants
      taxonomic recognition and active protection.

PMID- 29200919
TI  - Sexual morphs of Pterocomma tremulae Borner, 1940 (Aphididae, Aphidinae) with
      description of male reproductive system.
AB  - Paper presents the first description of the so far unknown sexual generation of
      Pterocomma tremulae (Aphididae, Aphidinae): oviparous female and alate male. It
      also provides detailed description of the male reproductive system. Discussion
      focuses on comparative analysis of male reproductive system with other aphid
      groups and possible importance of its structure in resolving phylogenetic
      interrelationships within the genus Pterocomma. A key is provided to the known
      males of European Pterocomma species.

PMID- 29200920
TI  - A monograph of the Australopacific Saprininae (Coleoptera, Histeridae).
AB  - The Australopacific Saprininae, containing twelve genera and forty species, are
      reviewed, illustrated and keyed to genera and species. Two new genera,
      Australopachylopusgen. n. (New Zealand, type species Saprinus lepidulus Broun,
      1881) and Iridoprinusgen. n. (Australia, type species I. myrmecophilussp. n.) and
      four new species: Saprinus (Saprinus) rarus sp. n. (Australia), Saprinus
      (Saprinus) chathamensis sp. n. (Chatham Islands, New Zealand), Saprinus
      (Saprinus) pseudodetritus sp. n. (Chatham Islands, New Zealand) and Saprinus
      (Saprinus) pacificus sp. n. (Kiribati) are described. The Saprininae fauna of the
      Australopacific Region is a mixture of northern invaders that most likely arrived
      to the region in early Cenozoic by 'island hopping' from north (Hypocaccus,
      Hypocacculus, several Saprinus) and truly autochthonous taxa either with
      uncertain phylogenetic affinities (Iridoprinusgen. n., Saprinodes Lewis, 1891,
      Reichardtia Wenzel, 1944, Australopachylopusgen. n.), primitive Australopacific
      endemics (e.g. Tomogenius Marseul, 1862) or presumed relicts (several species of
      Saprinus Erichson, 1834). Several Saprininae taxa (Chalcionellus aeneovirens
      (Schmidt, 1890); (Gnathoncus rotundatus (Kugelann, 1792); G. communis (Marseul,
      1862); Euspilotus (Neosaprinus) rubriculus (Marseul, 1855); Hypocaccus (Nessus)
      interpunctatus interpunctatus (Schmidt, 1885); Saprinus (S.) chalcites (Illiger,
      1807) and Saprinus (S.) cupreus Erichson, 1834)) were introduced into the region
      with human activity. We report the first cases of myrmecophily (Iridoprinus
      myrmecophilusgen. et sp. n.) and termitophily (Saprinus rarussp. n.) in the
      Saprininae from the Australopacific Region. Lectotypes and paralectotypes of the
      following taxa are designated herein: Saprinus amethystinus Lewis, 1900, Saprinus
      apricarius Erichson, 1834, Saprinus artensis Marseul, 1862, Saprinus auricollis
      Marseul, 1855, Saprinus australasiae Blackburn, 1903, Saprinus bistrigifrons
      Marseul, 1855, Saprinus certus Lewis, 1888, Saprinus communis Marseul, 1862,
      Saprinus cupreus Erichson, 1834, Saprinus cyanellus Marseul, 1855, Hister cyaneus
      Fabricius, 1775, Saprinus dentipes Marseul, 1855, Saprinus desbordesi Auzat,
      1916, Saprinus gayndahensis MacLeay, 1871, Saprinus hyla Marseul, 1864, Saprinus
      incisisternus Marseul, 1862, Saprinus incisus Erichson, 1842, Saprinus irinus
      Marseul, 1862, Saprinus laetus Erichson, 1834, Saprinus lepidulus Broun, 1881,
      Saprinus mastersii MacLeay, 1871, Saprinus nitiduloides Fairmaire, 1883, Saprinus
      pedator Sharp, 1876, Saprinus pseudocyaneus White, 1846, Saprinus rubriculus
      Marseul, 1855, Saprinus sinae Marseul, 1862, Saprinus tasmanicus Marseul, 1855,
      Saprinus tyrrhenus Blackburn, 1903, Saprinus varians Schmidt, 1890, Saprinus
      vernulus Blackburn, 1903, Saprinus viridanus Lewis, 1899, Saprinus viridipennis
      Lewis, 1901, and Saprinus westraliensis Blackburn, 1903. The synonymy of Saprinus
      tyrrhenus Blackburn, 1903 is revoked and the species is considered as valid
      (stat. n.). Seven new synonymies are proposed: Saprinus gayndahensis MacLeay,
      1871 = Saprinus laetus Erichson, 1834 syn. n., Saprinus pseudocyaneus White, 1846
      = Saprinus laetus Erichson, 1834 syn. n., Saprinus mastersii MacLeay, 1871 =
      Saprinus laetus Erichson, 1834 syn. n., Saprinus dentipes Marseul, 1855 =
      Hypocaccus (Baeckmanniolus) gaudens (J.L. LeConte, 1851) syn. n., Hypocaccus
      (Hypocaccus) vernulus (Blackburn, 1903) = Hypocaccus (Hypocaccus) sinae (Marseul,
      1862) syn. n., Saprinus (Saprinus) lindrothi Dahlgren, 1968 = Saprinus (Saprinus)
      prasinus Erichson, 1834 syn. n., and Saprinus (Saprinus) certus Lewis, 1888 =
      Saprinus (Saprinus) frontistrius Marseul, 1855 syn. n. The following new records
      are: Euspilotus (Neosaprinus) rubriculus (Marseul, 1855) (= Saprinus
      gnathoncoides Bickhardt, 1909) (Australia), Saprinus (Saprinus) laetus Erichson,
      1834 (Lord Howe Island) and Saprinus (Saprinus) cyaneus cyaneus (Fabricius, 1775)
      (Lord Howe Island and Fiji).

PMID- 29200921
TI  - New species and new records of earthworms of the genus Drawida from Kerala part
      of the Western Ghats biodiversity hotspot, India (Oligochaeta, Moniligastridae).
AB  - Two new species of Drawida Michaelsen, 1900, namely Drawida polydiverticulata
      Narayanan & Julka, sp. n. and Drawida thomasi Narayanan & Julka, sp. n., are
      described from material collected from the Indian state of Kerala, which lies in
      the Western Ghats biodiversity hotspot. Drawida elegans Rao, 1921, Drawida
      kanarensis Stephenson, 1917, Drawida modesta Rao, 1921, Drawida somavarpatana
      Rao, 1921, and Drawida thurstoni Gates, 1945 are recorded for the first time from
      the state.

PMID- 29200922
TI  - The Orthoptera of Castro Verde Special Protection Area (Southern Portugal): new
      data and conservation value.
AB  - With the increasing awareness of the need for Orthoptera conservation, greater
      efforts must be gathered to implement specific monitoring schemes. Despite recent
      surveys, little is known about Portuguese Orthoptera populations. This study was
      performed in 2014 and 2015 mainly in Castro Verde Special Protection Area (SPA),
      southern Portugal, and is the first Orthoptera inventory conducted in the area. A
      total of 35 Orthoptera species was recorded, with two new species reported for
      Portugal. We provide species' habitat occurrences within the protected area and
      use information on the conservation status and the Iberian distribution of each
      documented species to discuss the importance of Castro Verde SPA for Orthoptera
      conservation. The data presented here sheds new light on Castro Verde SPA
      biodiversity and emphasizes the inclusion of this area in the conservation of
      Orthoptera diversity, particularly in the protection of threatened endemic
      species.

PMID- 29200923
TI  - An annotated and illustrated checklist of Microgastrinae wasps (Hymenoptera,
      Braconidae) from the Canadian Arctic Archipelago and Greenland.
AB  - The Microgastrinae (Hymenoptera: Braconidae) from ten islands of the Canadian
      Arctic Archipelago (CAA) and Greenland were studied based on 2,183 specimens
      deposited in collections. We report a total of 33 species in six genera, more
      than doubling the totals previously known. Most of the species (75.7%) have a
      distribution restricted to the Nearctic, with nine of those (27.3%) confirmed to
      be High Arctic endemics and another 10 species considered very likely to be High
      Arctic endemics as well - accounting for all of those, more than half of all
      species found are endemic to the region. The most diverse genera were Cotesia (10
      species), Glyptapanteles (9 species), and Microplitis (7 species), representing
      78.8% of the overall species diversity in the region. The six most frequently
      collected species comprised 84.7% of all examined specimens. The flight period
      for Microgastrinae in the High Arctic encompasses only two months, with activity
      peaking during the first half of July, when almost 40% of all available specimens
      were collected, and then plummeting in the first half to the end of August.
      Microgastrinae wasps from the High Arctic are currently known to parasitize eight
      species within four families of Lepidoptera: three species of Noctuidae, two each
      of Lymantridae and Nymphalidae, and one species of Pterophoridae. However, that
      information is very preliminary, as only six of the 33 species of microgastrines
      currently have associated host data. An annotated checklist, including
      photographs for 24 of the 33 species, is provided, as well as a key to all
      Microgastrinae genera present in the region.

PMID- 29200924
TI  - Checklist of the flower flies of Ecuador (Diptera, Syrphidae).
AB  - Syrphidae is one of the most speciose families of true flies, with more than
      6,100 described species and worldwide distribution. They are important for humans
      acting as crucial pollinators, biological control agents, decomposers, and
      bioindicators. One third of its diversity is found in the Neotropical Region, but
      the taxonomic knowledge for this region is incomplete. Thus, taxonomic revisions
      and species checklists of Syrphidae in the Neotropics are the highest priority
      for biodiversity studies. Therefore, we present the first checklist of Syrphidae
      for Ecuador based on literature records, and provide as well the original
      reference for the first time species citations for the country. A total of 201
      species were recorded for Ecuador, with more than 600 records from 24 provinces
      and 237 localities. Tungurahua, Pastaza, and Galapagos were the best sampled
      provinces. Although the reported Ecuadorian syrphid fauna only comprises 11.2 %
      of the described Neotropical species, Ecuador has the third highest flower fly
      diversity density after Costa Rica and Suriname. These data indicate the high
      species diversity for this country in such small geographic area.

PMID- 29200925
TI  - Corrigenda: Revision of the Neotropical green lacewing genus Ungla (Neuroptera,
      Chrysopidae). ZooKeys 674: 1-188. https://doi.org/10.3897/zookeys.674.11435.
AB  - [This corrects the article DOI: 10.3897/zookeys.674.11435.].

PMID- 29200926
TI  - Manual of praying mantis morphology, nomenclature, and practices (Insecta,
      Mantodea).
AB  - This study provides a comprehensive review of historical morphological
      nomenclature used for praying mantis (Mantodea) morphology, which includes
      citations, original use, and assignment of homology. All referenced structures
      across historical works correspond to a proposed standard term for use in all
      subsequent works pertaining to praying mantis morphology and systematics. The new
      standards are presented with a verbal description in a glossary as well as
      indicated on illustrations and images. In the vast majority of cases, originally
      used terms were adopted as the new standard. In addition, historical
      morphological topographical homology conjectures are considered with discussion
      on modern interpretations. A new standardized formulation to present foreleg
      femoral and tibial spines is proposed for clarity based on previous works. In
      addition, descriptions for methods of collection, curation, genital complex
      dissection, and labeling are provided to aid in the proper preservation and
      storage of specimens for longevity and ease of study. Due to the lack of
      consistent linear morphometric measurement practices in the literature, we have
      proposed a series of measurements for taxonomic and morphological research. These
      measurements are presented with figures to provide visual aids with homologous
      landmarks to ensure compatibility and comparability across the Order. Finally,
      our proposed method of pinning mantises is presented with a photographical
      example as well as a video tutorial available at http://mantodearesearch.com.

PMID- 29200927
TI  - A taxonomic revision of Liogenys occurring in Brazil with an interactive key and
      remarks on New World Diplotaxini (Coleoptera, Melolonthidae).
AB  - Liogenys Guerin-Meneville, 1831 is the major genus of Neotropical Diplotaxini,
      with 78 species distributed from Panama to southern Argentina and Chile, except
      for Ecuador. Due to the large numbers of both described and undescribed species,
      as well as its agricultural importance, mainly of those in Brazil, Liogenys was
      redefined and redescribed. Nine new species are described: L. cavifrons Cherman,
      sp. n., L. femella Cherman, sp. n., L. piauiensis Cherman, sp. n., L.
      rotundicollis Cherman, sp. n., L. pseudosanctaecrucis Cherman, sp. n., L. grossii
      Cherman, sp. n., L. pseudospiniventris Cherman, sp. n., L. sulcoventris Cherman,
      sp. n., and L. freyi Cherman, sp. n. All the new species are Brazilian, except
      for the last one, which is Argentinian. Twenty-three Brazilian species are
      redescribed and illustrated. Five new synonyms are proposed, and 19 lectotypes
      are designated. New geographical distribution records for 19 species are
      presented, as well as a key to New World Diplotaxini and Brazilian species of
      Liogenys.

PMID- 29200928
TI  - Coelogyne magnifica (Orchidaceae), a new species from northern Myanmar.
AB  - Coelogyne magnifica (Orchidaceae), a new species from Putao, Kachin State,
      Myanmar, is described and illustrated. It belongs to Coelogyne section Ocellatae
      Pfitzer & Kraenzl. and it is morphologically similar to Coelogyne corymbosa and
      C. taronensis, but can be distinguished from these species by its larger flowers,
      lanceolate sepals and petals, a narrowly ovate lip, which has two bright yellow
      patches surrounded by shiny brownish red and two fimbriate or erose-lacerate
      lateral keels on the lip. The major differences between these species are
      outlined and discussed.

PMID- 29200929
TI  - Applications of deep convolutional neural networks to digitized natural history
      collections.
AB  - Natural history collections contain data that are critical for many scientific
      endeavors. Recent efforts in mass digitization are generating large datasets from
      these collections that can provide unprecedented insight. Here, we present
      examples of how deep convolutional neural networks can be applied in analyses of
      imaged herbarium specimens. We first demonstrate that a convolutional neural
      network can detect mercury-stained specimens across a collection with 90%
      accuracy. We then show that such a network can correctly distinguish two
      morphologically similar plant families 96% of the time. Discarding the most
      challenging specimen images increases accuracy to 94% and 99%, respectively.
      These results highlight the importance of mass digitization and deep learning
      approaches and reveal how they can together deliver powerful new investigative
      tools.

PMID- 29200930
TI  - Survey on synergism effect of ketotifen in combination with pyrimethamine in
      treatment of acute murine toxoplasmosis.
AB  - Background: Standard treatment of toxoplasmosis is accompanied by severe side
      effects and low tolerability; accordingly, alternative medicines are critically
      needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate
      inhibitor of Toxoplasma gondii (T. gondii) parasite entrance into the host cells.
      Therefore, the focus of current study is characterization of the anti-Toxoplasma
      activity of KET in the acute phase of toxoplasmosis in murine model as pre
      treatment and post-treatment (before and after infection with RH strain). KET was
      used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination
      with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA
      was extracted from brain biopsies samples. Parasite load was calculated using
      Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target
      for at RE (a 529 bp repeat element) gene. Results: A significant difference
      between KET and control groups was observed (P < 0.001) in the pre-treatment and
      post-treatment groups. Both KET and the combination of KET and PYR showed a
      reduction in the parasite load in brain through the acute phase of the infection.
      2 mg/kg/day dose of KET resulted in higher anti-Toxoplasma activity (15,698
      parasites/ml) compared to 3 mg/kg/day dose of KET (72,898 parasites/ml) in brain
      in the pre-treatment group. In addition, KET combined with PYR significantly
      decreased the parasite load in the post-treatment group. Conclusions: Our results
      indicated that KET has both prophylactic and therapeutic effects on acute phases
      of the disease.

PMID- 29200931
TI  - Systematic review of early risk factors for life-course-persistent, adolescence
      limited, and late-onset offenders in prospective longitudinal studies.
AB  - This paper builds on our previous systematic review of prospective longitudinal
      studies and examines the early risk factors associated with life-course
      persistent offending (LCP), adolescence-limited (AL) and late-onset (LO)
      offending. Out of the 55 prospective longitudinal studies which theoretically
      could possess the relevant information, only four provided information about risk
      factors associated with the different offending types. An additional three
      provided data so that relevant analyses could be conducted. The results suggested
      that there was little evidence that specific early risk factors were associated
      with specific offending types. There was also limited evidence that specific risk
      factors predicted specific offending types when criminal career duration was
      included in the definitions of LCP, AL, and LO offending. However, LCP offenders
      tended to have a greater number of risk factors, and the magnitude of these was
      somewhat greater than for AL offenders, who in turn tended to have more risk
      factors (and of a greater magnitude) than LO offenders. LCP and AL offenders may
      differ more in degree (in the number and magnitude of risk factors) than in kind
      (in the specific risk factors that are predictive). Importantly, as the potential
      criminal career duration was increased in defining the offending types, those
      with longer careers tended to have more risk factors, but, LCP and AL offenders
      were not predicted by different risk factors. Much more research is needed on
      risk factors for offending types defined according to criminal career durations.

PMID- 29200932
TI  - Introduction of a new platform for parameter estimation of kinetically complex
      environmental systems.
AB  - A modeling framework (ReKinSim - Reaction Kinetics Simulator) is introduced,
      within which biogeochemical reactions in environmental systems can be described
      and inversely fitted to experimental data. Three key features of this simulation
      environment are: (1) a generic mathematical tool for solving sets of unlimited,
      arbitrary, non-linear ordinary differential equations; (2) no limitation to the
      number or type of reactions or other influential dynamics (e.g., isotope
      fractionation or small-scale mass-transfer limitations); (3) an easy to use and
      flexible module for nonlinear data-fitting. It allows users to easily define any
      kinetic model by a set of biogeochemical reactions relevant to the experimental
      application and to obtain the values of the kinetic parameters by fitting of the
      model to data. By allowing users to include the environmentally related processes
      and solving them along with the chemical kinetics, ReKinSim helps the user to
      elucidate the extent that these processes are controlled by factors other than
      kinetics. The novelty of the presented program primary lays in its unique
      combination of flexibility, computational efficiency and user-friendliness.
      ReKinSim's usability is showcased by four case studies of varying complexity, and
      compared against a set of currently available modeling tools.

PMID- 29200934
TI  - Sparse graphs using exchangeable random measures.
AB  - Statistical network modelling has focused on representing the graph as a discrete
      structure, namely the adjacency matrix. When assuming exchangeability of this
      array-which can aid in modelling, computations and theoretical analysis-the
      Aldous-Hoover theorem informs us that the graph is necessarily either dense or
      empty. We instead consider representing the graph as an exchangeable random
      measure and appeal to the Kallenberg representation theorem for this object. We
      explore using completely random measures (CRMs) to define the exchangeable random
      measure, and we show how our CRM construction enables us to achieve sparse graphs
      while maintaining the attractive properties of exchangeability. We relate the
      sparsity of the graph to the Levy measure defining the CRM. For a specific choice
      of CRM, our graphs can be tuned from dense to sparse on the basis of a single
      parameter. We present a scalable Hamiltonian Monte Carlo algorithm for posterior
      inference, which we use to analyse network properties in a range of real data
      sets, including networks with hundreds of thousands of nodes and millions of
      edges.

PMID- 29200933
TI  - Dimensions of biodiversity loss: Spatial mismatch in land-use impacts on species,
      functional and phylogenetic diversity of European bees.
AB  - Aim: Agricultural intensification and urbanization are important drivers of
      biodiversity change in Europe. Different aspects of bee community diversity vary
      in their sensitivity to these pressures, as well as independently influencing
      ecosystem service provision (pollination). To obtain a more comprehensive
      understanding of human impacts on bee diversity across Europe, we assess
      multiple, complementary indices of diversity. Location: One Thousand four hundred
      and forty six sites across Europe. Methods: We collated data on bee occurrence
      and abundance from the published literature and supplemented them with the
      PREDICTS database. Using Rao's Quadratic Entropy, we assessed how species,
      functional and phylogenetic diversity of 1,446 bee communities respond to land
      use characteristics including land-use class, cropland intensity, human
      population density and distance to roads. We combined these models with
      statistically downscaled estimates of land use in 2005 to estimate and map-at a
      scale of approximately 1 km2-the losses in diversity relative to semi
      natural/natural baseline (the predicted diversity of an uninhabited grid square,
      consisting only of semi-natural/natural vegetation). Results: We show that
      relative to the predicted local diversity in uninhabited semi-natural/natural
      habitat-half of all EU27 countries have lost over 10% of their average local
      species diversity and two-thirds of countries have lost over 5% of their average
      local functional and phylogenetic diversity. All diversity measures were
      generally lower in pasture and higher-intensity cropland than in semi
      natural/natural vegetation, but facets of diversity showed less consistent
      responses to human population density. These differences have led to marked
      spatial mismatches in losses: losses in phylogenetic diversity were in some areas
      almost 20 percentage points (pp.) more severe than losses in species diversity,
      but in other areas losses were almost 40 pp. less severe. Main conclusions: These
      results highlight the importance of exploring multiple measures of diversity when
      prioritizing and evaluating conservation actions, as species-diverse assemblages
      may be phylogenetically and functionally impoverished, potentially threatening
      pollination service provision.

PMID- 29200935
TI  - Was the Mw 7.5 1952 Kern County, California, earthquake induced (or triggered)?
AB  - Several recent studies have presented evidence that significant induced
      earthquakes occurred in a number of oil-producing regions during the early and
      mid-twentieth century related to either production or wastewater injection. We
      consider whether the 21 July 1952 Mw 7.5 Kern County earthquake might have been
      induced by production in the Wheeler Ridge oil field. The mainshock, which was
      not preceded by any significant foreshocks, occurred 98 days after the initial
      production of oil in Eocene strata at depths reaching 3 km, within ~1 km of the
      White Wolf fault (WWF). Based on this spatial and temporal proximity, we explore
      a potential causal relationship between the earthquake and oil production. While
      production would have normally be expected to have reduced pore pressure,
      inhibiting failure on the WWF, we present an analytical model based on industry
      stratigraphic data and best estimates of parameters whereby an impermeable splay
      fault adjacent to the main WWF could plausibly have blocked direct pore pressure
      effects, allowing the poroelastic stress change associated with production to
      destabilize the WWF, promoting initial failure. This proof-of-concept model can
      also account for the 98-day delay between the onset of production and the
      earthquake. While the earthquake clearly released stored tectonic stress, any
      initial perturbation on or near a major fault system can trigger a larger
      rupture. Our proposed mechanism provides an explanation for why significant
      earthquakes are not commonly induced by production in proximity to major faults.

PMID- 29200936
TI  - Dynamical boson stars.
AB  - The idea of stable, localized bundles of energy has strong appeal as a model for
      particles. In the 1950s, John Wheeler envisioned such bundles as smooth
      configurations of electromagnetic energy that he called geons, but none were
      found. Instead, particle-like solutions were found in the late 1960s with the
      addition of a scalar field, and these were given the name boson stars. Since
      then, boson stars find use in a wide variety of models as sources of dark matter,
      as black hole mimickers, in simple models of binary systems, and as a tool in
      finding black holes in higher dimensions with only a single Killing vector. We
      discuss important varieties of boson stars, their dynamic properties, and some of
      their uses, concentrating on recent efforts.

PMID- 29200937
TI  - Diverse modes of reactivity of 6-(chloromethyl)-6-methylfulvene.
AB  - The title compound exhibits a number of reactivities toward nucleophiles/bases
      owing to the presence of several electrophilic and potentially nucleophilic sites
      in the molecule. We explored the reactions of 6-(chloromethyl)-6-methylfulvene
      with oxygen- and nitrogen nucleophiles and bases as well as a carbon-based
      nucleophile (an enamine) and realized all possible reactivity modes predicted on
      the basis of electrophilic and nucleophilic positions in this compound.

PMID- 29200938
TI  - Cyclopentadienones via a tandem C-cyclopropylnitrone cyclization-cycloreversion
      sequence.
AB  - Aldonitrones derived from spiro[2.4]hepta-4,6-diene-1-carbaldehyde and its benzo
      analog undergo a tandem uncatalyzed intramolecular cyclopropane-nitrone
      cyclization-5,6-dihydro-1,2-oxazine cycloreversion to give cyclopentadienones.
      Similarly, the NH-nitrone generated in situ from spiro[cyclopropane-1,1'
      indene]carbaldehyde oxime leads to benzocyclopentadienone (1H-inden-1-one) by the
      same mechanism. DFT calculations are in favor of a concerted yet highly
      asynchronous pathway for the cyclizations. Control experiments with the dihydro
      and tetrahydro derivatives show that the spirocyclopentadiene unit is essential
      for the success of the reaction, invoking spiroconjugative effects for increased
      cyclopropane reactivity.

PMID- 29200939
TI  - Photochemical Properties and Structure-Activity Relationships of RuII Complexes
      with Pyridylbenzazole Ligands as Promising Anticancer Agents.
AB  - Ruthenium complexes capable of light-triggered cytotoxicity are appealing
      potential prodrugs for photodynamic therapy (PDT) and photoactivated chemotherapy
      (PACT). Two groups of Ru(II) polypyridyl complexes with 2-(2-pyridyl)-benzazole
      ligands were synthesized and investigated for their photochemical properties and
      anticancer activity to compare strained and unstrained systems that are likely to
      have different biological mechanisms of action. The structure-activity
      relationship was focused on the benzazole core bioisosterism and replacement of
      coligands in Ru(II) complexes. Strained compounds rapidly ejected the 2-(2
      pyridyl)-benzazole ligand after light irradiation, and possessed strong toxicity
      in the HL-60 cell line both under dark and light conditions. In contrast,
      unstrained Ru(II) complexes were non-toxic in the absence of light, induced
      cytotoxicity at nanomolar concentrations after light irradiation, and are capable
      of light-induced DNA damage. The 90-220-fold difference in light and dark IC50
      values provides a large potential therapeutic window to allow for selective
      targeting of cells by exposure to light.

PMID- 29200940
TI  - Palatini wormholes and energy conditions from the prism of general relativity.
AB  - Wormholes are hypothetical shortcuts in spacetime that in general relativity
      unavoidably violate all of the pointwise energy conditions. In this paper, we
      consider several wormhole spacetimes that, as opposed to the standard designer
      procedure frequently employed in the literature, arise directly from
      gravitational actions including additional terms resulting from contractions of
      the Ricci tensor with the metric, and which are formulated assuming independence
      between metric and connection (Palatini approach). We reinterpret such wormhole
      solutions under the prism of General Relativity and study the matter sources that
      thread them. We discuss the size of violation of the energy conditions in
      different cases and how this is related to the same spacetimes when viewed from
      the modified gravity side.

PMID- 29200943
TI  - Cancer-related post-treatment pain and its impact on health-related quality of
      life in breast cancer patients: a cross sectional study in Palestine.
AB  - Background: Post-treatment pain has been suggested as an important indicator for
      health-related quality of life (HRQOL) in patients with breast cancer. Therefore,
      this study was performed to examine the association between pain and its impact
      on HRQOL among breast cancer patients in Palestine. Also, this study aimed to
      determine the QOL profile for breast cancer patients and stated the factors
      associated with QOL. Methods: A correlational cross-sectional study was conducted
      from May 2016 to November 2016 at Al-Watani Hospital and An-Najah National
      University Hospital in the Nablus district in Palestine. The five-level EuroQol
      five-dimensional instrument (EQ-5D-5L) was used to examine HRQOL. Pain severity
      and interference were assessed using the Brief Pain Inventory (BPI). Multiple
      linear regression analysis was performed to determine the most important
      variables related with HRQOL. Results: One hundred and seventy patients were
      involved in this study. Overall, all participants were female, with a mean +/- SD
      for age of 51.71 +/- 11.11 years. The reported HRQOL of this study was measured
      by using the median EQ-5D-5L index score, which was 0.67 (interquartile range:
      0.51-0.84). There were moderate negative correlations between EQ-5D-5L index
      score and pain severity score (r = - 0.58, p value < 0.001), and pain
      interference score (r = - 0.604, p-value < 0.001). Furthermore, univariate
      analysis showed that age, marital status, employment status, income, current
      condition of cancer, and post-treatment pain were associated with quality of life
      (p-value < 0.05). Regression analysis revealed that patients with high income (p
      value = 0.003), patients with lower pain severity score (p-value < 0.001), and
      lower pain interference score (p-value = 0.018) were independently associated
      with high QOL. Conclusions: This is the first study to present important data
      regarding QOL by using the EQ-5D-5L instruments that may help healthcare
      providers to identify patients at risk of low QOL. Healthcare providers and
      health strategy makers should be alerted to low level HRQOL among breast cancer
      patients with low income level, patients with post-treatment pain, especially in
      the state of severe pain, and the state of pain interfering with daily life to
      improve their HRQOL.

PMID- 29200945
TI  - Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol
      3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In
      Rats.
AB  - The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)
      methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The
      aim of this research investigation was to evaluate the acute toxicity and the
      ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat
      model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy
      methyl cellulose) for the normal and ulcer control groups each, Omeprazole
      (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for
      experimental groups, respectively. After one hour, instead of rats in the normal
      group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of
      HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice,
      gastric mucosa, morphologies of gastric ulcers and protein expressions of both
      control and treatment groups were evaluated. TIBH showed a ulcer prevention
      potential by increase of the mucus secretion, decrease of the gastric acidity, up
      regulation of HSP70 protein, down-regulation of Bax protein, decrease of the
      lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in
      gastric tissue homogenate. Acute toxicity assay exposed valuable information on
      the safety of this compound. TIBH had a dose dependent ulcer prevention potential
      against HCl/Ethanol-triggered gastric ulcer.

PMID- 29200944
TI  - Cost Utility Analysis of Cervical Therapeutic Medial Branch Blocks in Managing
      Chronic Neck Pain.
AB  - Background: Controlled diagnostic studies have established the prevalence of
      cervical facet joint pain to range from 36% to 67% based on the criterion
      standard of >= 80% pain relief. Treatment of cervical facet joint pain has been
      described with Level II evidence of effectiveness for therapeutic facet joint
      nerve blocks and radiofrequency neurotomy and with no significant evidence for
      intraarticular injections. However, there have not been any cost effectiveness or
      cost utility analysis studies performed in managing chronic neck pain with or
      without headaches with cervical facet joint interventions. Study Design: Cost
      utility analysis based on the results of a double-blind, randomized, controlled
      trial of cervical therapeutic medial branch blocks in managing chronic neck pain.
      Objectives: To assess cost utility of therapeutic cervical medial branch blocks
      in managing chronic neck pain. Methods: A randomized trial was conducted in a
      specialty referral private practice interventional pain management center in the
      United States. This trial assessed the clinical effectiveness of therapeutic
      cervical medial branch blocks with or without steroids for an established
      diagnosis of cervical facet joint pain by means of controlled diagnostic blocks.
      Cost utility analysis was performed with direct payment data for the procedures
      for a total of 120 patients over a period of 2 years from this trial based on
      reimbursement rates of 2016. The payment data provided direct procedural costs
      without inclusion of drug treatments. An additional 40% was added to procedural
      costs with multiplication of a factor of 1.67 to provide estimated total costs
      including direct and indirect costs, based on highly regarded surgical
      literature. Outcome measures included significant improvement defined as at least
      a 50% improvement with reduction in pain and disability status with a combined
      50% or more reduction in pain in Neck Disability Index (NDI) scores. Results: The
      results showed direct procedural costs per one-year improvement in quality
      adjusted life year (QALY) of United States Dollar (USD) of $2,552, and overall
      costs of USD $4,261. Overall, each patient on average received 5.7 +/- 2.2
      procedures over a period of 2 years. Average significant improvement per
      procedure was 15.6 +/- 12.3 weeks and average significant improvement in 2 years
      per patient was 86.0 +/- 24.6 weeks. Limitations: The limitations of this cost
      utility analysis are that data are based on a single center evaluation. Only
      costs of therapeutic interventional procedures and physician visits were
      included, with extrapolation of indirect costs. Conclusion: The cost utility
      analysis of therapeutic cervical medial branch blocks in the treatment of chronic
      neck pain non-responsive to conservative management demonstrated clinical
      effectiveness and cost utility at USD $4,261 per one year of QALY.

PMID- 29200946
TI  - Combined Hemorrhagic Shock and Unilateral Common Carotid Occlusion Induces
      Neurological Injury in Adult Male Rats.
AB  - Background: Clinical assessment reveals that patients after surgery of
      cardiopulmonary bypass or coronary bypass experience postoperative cognitive
      dysfunction. This study aimed to investigate whether resuscitation after a
      hemorrhagic shock (HS) and/or mild cerebral ischemia caused by a unilateral
      common carotid artery occlusion (UCCAO) can cause brain injury and concomitant
      neurological dysfunction, and explore the potential mechanisms. Methods: Blood
      withdrawal (6 mL/100 g body weight) for 60 min through the right jugular vein
      catheter-induced an HS. Immediately after the termination of HS, we reinfused the
      initially shed blood volumes to restore and maintain the mean arterial blood
      pressure (MABP) to the original value during the 30-min resuscitation. A cooling
      water blanket used to induce whole body cooling for 30 min after the end of
      resuscitation. Results: An UCCAO caused a slight cerebral ischemia (cerebral
      blood flow [CBF] 70%) without hypotension (MABP 85 mmHg), systemic inflammation,
      multiple organs injuries, or neurological injury. An HS caused a moderate
      cerebral ischemia (52% of the original CBF levels), a moderate hypotension (MABP
      downed to 22 mmHg), systemic inflammation, and peripheral organs injuries.
      However, combined an UCCAO and an HS caused a severe cerebral ischemia (18% of
      the original CBF levels), a moderate hypotension (MABP downed to 17 mmHg),
      systemic inflammation, peripheral organs damage, and neurological injury, which
      can be attenuated by whole body cooling. Conclusions: When combined with an HS,
      an UCCAO is associated with ischemic neuronal injury in the ipsilateral
      hemisphere of adult rat brain, which can be attenuated by therapeutic
      hypothermia. A resuscitation from an HS regards as a reperfusion insult which may
      induce neurological injury in patients with an UCCAO disease.

PMID- 29200947
TI  - HSPB8 Promotes the Fusion of Autophagosome and Lysosome during Autophagy in
      Diabetic Neurons.
AB  - Although autophagy has been proposed to play an emerging role in diabetic
      neuropathy, autophagy and its possible role remains unclear. Moreover, only few
      studies about diabetes have explored the autophagy mediated by heat shock protein
      beta-8 (HSPB8) and Bcl-2 associated athanogene 3 (BAG3). In the present study, we
      examined the autophagy induced by high glucose levels in an in vivo rat model of
      diabetes induced by streptozotocin (STZ) and an in vitro model of retinal
      ganglion cell-5 (RGC5) cells under high glucose conditions. In the spinal cord
      tissues of the STZ-induced diabetic rats, the levels of light chain 3 (LC3) and
      Beclin-1-marked autophagy rose with increasing HSPB8 and BAG3 levels. By confocal
      immunofluorescence, HSPB8 and LC3 were observed to be co-localized in the spinal
      cord tissues. In the RGC5 cells, high-glucose stimulation upregulated the
      expression of LC3-II, Beclin-1, and HSPB8 in a dose-dependent manner. When the
      RGC5 cells were subjected to high-glucose conditions, HSPB8 overexpression, along
      with upregulated LC3-II and Beclin-1 expression, increased the autophagic rate,
      whereas siRNA-silenced HSPB8 decreased the autophagic rate. Furthermore, in GFP
      mRFP-LC3 probe experiments, HSPB8 overexpression promoted autophagosome-lysosome
      fusion, whereas HSPB8 silencing disrupted this process. In the cells treated with
      HSPB8 and siRNA, the fusion was impaired, as indicated by the elevated p62
      expression. HSPB8 overexpression can partly rescue the blocking of the autophagy
      flux with chloroquine through the reduction of p62 expression level. Our study
      demonstrated that HSPB8 is involved in the high glucose-induced autophagy under
      the in vivo and in vitro conditions and critically participated in the
      autophagosome-lysosome fusion during the autophagy flux.

PMID- 29200950
TI  - Isolation and determination of four potential antimicrobial components from
      Pseudomonas aeruginosa extracts.
AB  - Background:Pseudomonas aeruginosa can cause disease and also can be isolated from
      the skin of healthy people. Additionally, it exhibits certain antimicrobial
      effects against other microorganisms.Methods: We collected 60 strains of P.
      aeruginosa and screened their antimicrobial effects against Staphylococcus aureus
      (ATCC 25923) using the filter paper-disk method, the cross-streaking method and
      the co-culture method and then evaluated the antimicrobial activity of the
      chloroform-isolated S. aureus extracts against methicillin-resistant S. aureus
      (MRSA, Gram-positive cocci), vancomycin intermediate-resistant S. aureus (VISA,
      Gram-positive cocci), Corynebacterium spp. (CS, Gram-positive bacilli),
      Acinetobacter baumannii (AB, Gram-negative bacilli), Moraxella catarrhalis (MC,
      Gram-negative diplococcus), Candida albicans (CA, fungi), Candida tropicalis (CT,
      fungi), Candida glabrata (CG, fungi) and Candida parapsilosis (CP, fungi).
      Results: The PA06 and PA46 strains have strong antimicrobial effects. High
      performance liquid chromatography (HPLC) analysis revealed that the major
      components of PA06 and PA46 that exhibit antimicrobial activity are functionally
      similar to phenazine-1-carboxylic acid (PCA) and pyocyanin. Preparative HPLC was
      performed to separate and isolate the 4 major potential antimicrobial components:
      PA06ER10, PA06ER16, PA06ER23 and PA06ER31. Further, the molecular masses of
      PA06ER10 (260.1), PA06ER16 (274.1), PA06ER23 (286.1) and PA06ER31 (318.2) were
      determined by electrospray ionization (ESI) mass spectrometry. Conclusion:P.
      aeruginosa can produce small molecules with potential antimicrobial activities
      against MRSA, VISA, CS, MC, CA, CT, CG and CP but not against AB.

PMID- 29200948
TI  - Peptides as Therapeutic Agents for Dengue Virus.
AB  - Dengue is an important global threat caused by dengue virus (DENV) that records
      an estimated 390 million infections annually. Despite the availability of CYD-TDV
      as a commercial vaccine, its long-term efficacy against all four dengue virus
      serotypes remains unsatisfactory. There is therefore an urgent need for the
      development of antiviral drugs for the treatment of dengue. Peptide was once a
      neglected choice of medical treatment but it has lately regained interest from
      the pharmaceutical industry following pioneering advancements in technology. In
      this review, the design of peptide drugs, antiviral activities and mechanisms of
      peptides and peptidomimetics (modified peptides) action against dengue virus are
      discussed. The development of peptides as inhibitors for viral entry, replication
      and translation is also described, with a focus on the three main targets,
      namely, the host cell receptors, viral structural proteins and viral non
      structural proteins. The antiviral peptides designed based on these approaches
      may lead to the discovery of novel anti-DENV therapeutics that can treat dengue
      patients.

PMID- 29200951
TI  - The Clinical Usefulness of Measurement of Visceral Fat Area Using Multi-Frequency
      Bioimpedance: The Association with Cardiac and Renal Function In General
      Population with Relatively Normal Renal Function.
AB  - Background: This study was performed to determine the clinical usefulness of
      measurement of visceral fat area (VFA) using bioimpedance analysis in relation
      with left ventricular hypertrophy (LVH), diastolic dysfunction parameters, and
      decreased estimated glomerular filtration rate (eGFR). Methods: A cross-sectional
      analysis was performed on 1028 patients with eGFR>=60 ml/min/1.73m2, aged 40 - 64
      years, and who underwent routine health check-ups. Subjects were divided into
      tertiles based on their VFA. Associations of VFA with echocardiographic
      parameters and eGFR were evaluated. Results: Across the VFA teriltes, there was a
      significant trend for increasing left ventricular mass index (LVMi), left atrial
      diameter (LAD), and ratio of early mitral inflow velocity to peak mitral annulus
      velocity (E/E' ratio) and that for decreasing ratio of early to late mitral
      inflow peak velocities (E/A ratio) and eGFR. In multivariate linear regression
      analysis, log-transformed VFA was significantly associated with increased LVMi,
      LAD, and E/E' ratio, and with decreased E/A ratio and eGFR. After adjustment for
      body mass index, log-transformed VFA remained as a significant determinant for
      E/A ratio. Conclusion: VFA may be associated with LV structure and diastolic
      function, and decreased eGFR in middle-aged adults with normal or mildly impaired
      renal function.

PMID- 29200949
TI  - Over-expression of Activated Signal Transducer and Activator of Transcription 3
      Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.
AB  - Background: Signal transducer and activator of transcription proteins (STATs)
      play important roles in gene regulation, cell proliferation, and cell
      differentiation. We aimed to establish the relationship between phosphorylated
      STAT3 (p-Ser-STAT3) expression and the prognosis of upper tract urothelial
      carcinoma (UTUC). Methods: This study retrospectively reviewed 100 patients with
      pathologically confirmed UTUC at Kaohsiung Medical University Hospital. We
      quantified the expression of p-Ser-STAT3 in cancer cells by immunohistochemistry,
      and determined the clinicopathological significance of p-Ser-STAT3 expression and
      prognostic outcomes in patients with UTUC. Results: High p-Ser-STAT3 expression
      was detected in 52% of UTUC patients. High p-Ser-STAT3 expression was associated
      with poor recurrence-free survival (p = 0.018) and overall survival (p = 0.026).
      In advanced cancer samples (stage T3/T4), p-Ser-STAT3 expression is the only
      independent prognostic factor for recurrence-free survival (hazard ratio = 5.91,
      p = 0.01) and cancer-specific survival (hazard ratio = 8.83, p = 0.039).
      Conclusions: The expression of p-Ser-STAT3 can be a potential prognostic marker
      for cancer recurrence and survival in UTUC, especially in advanced stage cases.

PMID- 29200952
TI  - Prognostic significance of high-mobility group box protein 1 genetic
      polymorphisms in rheumatoid arthritis disease outcome.
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes chronic
      inflammation of the joints. Analysis of genetic variants offers promise for
      guiding treatment and improving outcomes in RA. High-mobility group box protein 1
      (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that
      participates in several biological functions including immune response, cell
      survival and apoptosis. We investigated the effects of HMGB1 gene polymorphisms
      on the risk of RA disease progression in a cohort of Chinese Han individuals.
      Four single nucleotide polymorphisms (SNPs) from the HMGB1 gene were selected and
      genotyped in 232 patients with RA and 353 healthy controls. We found that having
      one C allele in rs1360485 and one G allele in rs2249825 polymorphisms lowered the
      risk of RA in females. Moreover, among healthy controls, those who bore the C/G/T
      haplotype at SNPs rs1360485, rs2249825 and rs1412125 were at reduced risk of
      developing RA by 0.13-fold (p <0.05). This is the first report to examine the
      risk factors associated with HMGB1 SNPs in the development of RA disease in the
      Chinese Han population.

PMID- 29200953
TI  - Effects of Osteogenic-Conditioned Medium from Human Periosteum-Derived Cells on
      Osteoclast Differentiation.
AB  - Stem/progenitor cell-based regenerative medicine using the osteoblast
      differentiation of mesenchymal stem cells (MSCs) is regarded as a promising
      approach for the therapeutic treatment of various bone defects. The effects of
      the osteogenic differentiation of stem/progenitor cells on osteoclast
      differentiation may have important implications for use in therapy. However,
      there is little data regarding the expression of osteoclastogenic proteins during
      osteoblastic differentiation of human periosteum-derived cells (hPDCs) and
      whether factors expressed during this process can modulate osteoclastogenesis. In
      the present study, we measured expression of RANKL in hPDCs undergoing
      osteoblastic differentiation and found that expression of RANKL mRNA was markedly
      increased in these cells in a time-dependent manner. RANKL protein expression was
      also significantly enhanced in osteogenic-conditioned media from hPDCs undergoing
      osteoblastic differentiation. We then isolated and cultured CD34+ hematopoietic
      stem cells (HSCs) from umbilical cord blood (UCB) mononuclear cells (MNCs) and
      found that these cells were well differentiated into several hematopoietic
      lineages. Finally, we co-cultured human trabecular bone osteoblasts (hOBs) with
      CD34+ HSCs and used the conditioned medium, collected from hPDCs during
      osteoblastic differentiation, to investigate whether factors produced during
      osteoblast maturation can affect osteoclast differentiation. Specifically, we
      measured the effect of this osteogenic-conditioned media on expression of
      osteoclastogenic markers and osteoclast cell number. We found that osteoclastic
      marker gene expression was highest in co-cultures incubated with the conditioned
      medium collected from hPDCs with the greatest level of osteogenic maturation.
      Although further study will be needed to clarify the precise mechanisms that
      underlie osteogenic-conditioned medium-regulated osteoclastogenesis, our results
      suggest that the osteogenic maturation of hPDCs could promote osteoclastic
      potential.

PMID- 29200954
TI  - Reprogramming Factors Remodel Melanoma Cell Phenotype by Changing Stat3
      Expression.
AB  - The limited availability of melanoma stem cells is a major challenge for
      therapeutic reagent screening and study of molecular mechanisms. It has been
      shown that induced expression of four stem cell factors (Oct4, Sox2, Klf4, and c
      Myc) changes the phenotype of osteosarcoma and breast cancer cells to
      osteosarcoma stem cells and breast cancer stem cells, respectively. The present
      study aimed to explore whether these four factors might change the phenotype of
      melanoma cells to melanoma stem cells and, if so, to examine the possible
      molecular signal involved. Melanoma B16-F10 cells were transfected with the
      plasmid TetO-FUW-OSKM which contains cDNA expressing four factors, driven by the
      Tet-On element. We found that expression of the four transcription factors was
      highly induced by DOX in the stable melanoma cell clones. Further studies
      confirmed that induced expression of these factors remodeled the phenotype of the
      melanoma cells to melanoma stem cells (MSCs). This conclusion was supported by
      the evidence that induced expression of these factors increased the numbers of
      tumor-initiating cells, (namely MSCs), both in an in vitro cell culture system
      and in a mouse in vivo model. The conclusion was further supported by the
      observation that the induction of these factors exclusively increased the mRNA of
      signal transducer and activator of transcription 3 which has been reported to
      play a crucial role in stem cell maintenance. Thus, phenotypic remodeling of
      melanoma cells following the induction of these four factors provided a simple
      and optimal means to constantly obtain MSCs for screening new therapeutic
      reagents. The result also reveals that Stat3 may be a crucial link between the
      induction of the four factors and the cell remodeling, suggesting its potential
      role as a target to fight melanoma.

PMID- 29200955
TI  - Evaluating the Prognostic Value of ERCC1 and Thymidylate Synthase Expression and
      the Epidermal Growth Factor Receptor Mutation Status in Adenocarcinoma Non-Small
      Cell Lung Cancer.
AB  - The present study evaluated the prognostic value of the epidermal growth factor
      receptor (EGFR) mutation status, and excision repair cross-complementation group
      1 (ERCC1) and thymidylate synthase (TS) expression following intercalated
      tyrosine kinase inhibitor (TKI) therapy and platinum- and pemetrexed-based
      chemotherapies (subsequent second-line treatment) for patients with
      adenocarcinoma non-small-cell lung cancer (AC-NSCLC). In total, 131 patients with
      AC-NSCLC were enrolled. The EGFR mutation status and ERCC1 and TS expression were
      evaluated through direct DNA sequencing and immunohistochemical analyses,
      respectively. The EGFR mutation status and ERCC1 and TS expression were the
      significant predictors of clinical outcomes. The EGFR mutation status was the
      main outcome predictor for overall survival (OS) benefits in the overall
      population. Further exploratory ERCC1 and TS expression analyses were conducted
      to provide additional insights. Low TS expression was predictive of improved OS
      of patients with negative EGFR-mutated advanced AC-NSCLC, whereas high ERCC1
      expression resulted in poor OS in patients with positive EGFR-mutated advanced AC
      NSCLC. TS and ERCC1 expression levels were effective prognostic factors for
      negative and positive EGFR-mutated AC-NSCLC, respectively. In conclusion, the
      present results indicate that the EGFR mutation status and TS and ERCC1
      expression can be used as the predictors of OS after subsequent second-line
      treatments for AC-NSCLC.

PMID- 29200956
TI  - Stem Cells from Cryopreserved Human Dental Pulp Tissues Sequentially
      Differentiate into Definitive Endoderm and Hepatocyte-Like Cells in vitro.
AB  - We previously described a novel tissue cryopreservation protocol to enable the
      safe preservation of various autologous stem cell sources. The present study
      characterized the stem cells derived from long-term cryopreserved dental pulp
      tissues (hDPSCs-cryo) and analyzed their differentiation into definitive endoderm
      (DE) and hepatocyte-like cells (HLCs) in vitro. Human dental pulp tissues from
      extracted wisdom teeth were cryopreserved as per a slow freezing tissue
      cryopreservation protocol for at least a year. Characteristics of hDPSCs-cryo
      were compared to those of stem cells from fresh dental pulps (hDPSCs-fresh).
      hDPSCs-cryo were differentiated into DE cells in vitro with Activin A as per the
      Wnt3a protocol for 6 days. These cells were further differentiated into HLCs in
      the presence of growth factors until day 30. hDPSCs-fresh and hDPSCs-cryo
      displayed similar cell growth morphology, cell proliferation rates, and
      mesenchymal stem cell character. During differentiation into DE and HLCs in
      vitro, the cells flattened and became polygonal in shape, and finally adopted a
      hepatocyte-like shape. The differentiated DE cells at day 6 and HLCs at day 30
      displayed significantly increased DE- and hepatocyte-specific markers at the mRNA
      and protein level, respectively. In addition, the differentiated HLCs showed
      detoxification and glycogen storage capacities, indicating they could share
      multiple functions with real hepatocytes. These data conclusively show that
      hPDSCs-cryo derived from long-term cryopreserved dental pulp tissues can be
      successfully differentiated into DE and functional hepatocytes in vitro. Thus,
      preservation of dental tissues could provide a valuable source of autologous stem
      cells for tissue engineering.

PMID- 29200957
TI  - ZW800-1 for Assessment of Blood-Brain Barrier Disruption in a Photothrombotic
      Stroke Model.
AB  - Background: Since it is known that serum albumin-bound dyes can cross the blood
      brain barrier (BBB) after ischemia, Evans Blue dye is commonly used to assess BBB
      disruption because of its rapid binding to serum albumin. In addition,
      indocyanine green (ICG), a clinically available dye, binds to serum proteins that
      could also be used for assessment of BBB impairment. Unlike these near-infrared
      (NIR) dyes, zwitterionic NIR fluorophore (ZW800-1) shows no serum binding,
      ultralow non-specific tissue uptake, and rapid elimination from the body via
      renal filtration. In this study, we report the use of ZW800-1 as a NIR
      fluorescence imaging agent for detecting BBB disruption in rat stroke models.
      Methods: Three types of NIR fluorophores, Evans Blue, ICG, and ZW800-1, were
      administered intraperitoneally into rat photothrombotic stroke models by using 4%
      concentration of each NIR dye. The NIR fluorescence signals in the infarcted
      brain tissue and biodistribution were observed in real-time using the Mini
      FLARE(r) imaging system up to 24 h post-injection. Results: ZW800-1 provided
      successful visualization of the ischemic injury site in the brain tissue, while
      the remaining injected dye was clearly excreted from the body within a certain
      period of time. Although Evans Blue and ICG provided mapping of the infarcted
      brain lesions, they exhibited high non-specific uptake in most of the tissues and
      organs and persisted in the body over 24 h post-injection. Conclusion: Our
      results suggest the promising application of ZW800-1 as a new strategy in BBB
      experiments and future therapeutic development.

PMID- 29200958
TI  - Introductory Dialogue and the Kohler Effect in Software-Generated Workout
      Partners.
AB  - Objectives: This study explored the Kohler motivation gain effect utilizing
      adults and software-generated partners (SGPs) during an abdominal exercise
      regimen and compared the type of participant-SGP introductory dialogue as a
      moderator. The Kohler effect applies interdependent team dynamics in which group
      performance is dependent upon the weaker member. The third objective was to
      examine if this motivation paradigm would result in adverse consequences to
      secondary variables: exertion, enjoyment, and self-efficacy beliefs. Design:
      Adults (Mage = 38.8 +/- 7.7) were randomly assigned to 1 of 3 conditions:
      Interactive Partner SGP (IP), Linear Dialogue Partner SGP (LDP), or individual
      control (IC), to complete a series of abdominal exercises. The experiment used a
      3 (condition) x 2 (gender) ANCOVA design, with a baseline block of exercises as a
      covariate. Method: Participants completed abdominal exercises individually and,
      after a rest, repeated the same exercises with either an SGP programmed to be
      moderately stronger or individually (IC). Prior to the second exercise block, IP
      participants interacted with the SGP using a dialog tree optional-response
      format. The LDP participant introduction was a linear, scripted exchange of basic
      information. Results: The LDP and IP conditions persisted significantly longer
      than IC, generating moderate effect sizes (d = .62; d = .76). The mean difference
      between partnered conditions was not significant. Conclusions: The Kohler
      motivation exercise paradigm resulted in a considerable increase in persistence
      (Madj = 28.9, SE = 10.6) in the first study to use middle-aged adults with
      superior SGPs. Differences between introductory dialogue methods were not
      significant.

PMID- 29200959
TI  - Polyphenols and health: Interactions between fibre, plant polyphenols and the gut
      microbiota.
AB  - A high-fibre diet and one rich in fruit and vegetables have long been associated
      with lower risk of chronic disease. There are several possible mechanisms
      underpinning these associations, but one likely important factor is the
      production of bioactive molecules from plant-based foods by the bacteria in the
      colon. This links to our growing understanding of the role of the gut microbiome
      in promoting health. Polyphenolic-rich plant foods have been associated with
      potential health effects in many studies, but the bioavailability of polyphenol
      compounds, as eaten, is often very low. Most of the ingested molecules enter the
      large intestine where they are catabolised to smaller phenolic acids that may be
      the key bioactive effectors. Dietary fibres, present in plant foods, are also
      fermented by the bacteria to short-chain fatty acids, compounds associated with
      several beneficial effects on cell turnover, metabolism and eating behaviour.
      Polyphenols and fibre are often eaten together, but there is a lack of research
      investigating the interaction between these two groups of key substrates for the
      colonic bacteria. In a project funded by the Biotechnology and Biological
      Sciences Research Council Diet and Health Research Industry Club, we are
      investigating whether combining different fibres and polyphenol sources can
      enhance the production of bioactive phenolic acids to promote health. This could
      lead to improved dietary recommendations and to new products with enhanced
      potential health-promoting actions.

PMID- 29200961
TI  - Posterior cerebral fossa medulloepithelioma: report of a case.
AB  - Background: Medulloepithelioma is a rare primitive neuroectodermal tumor of the
      central nervous system, usually developing in childhood. Due to its rarity, the
      optimal management is still unknown. The prognosis is poor, especially when
      resection is incomplete. Adjuvant radiochemotherapy is often indicated. Case
      presentation: We report a rare case of infratentorial medulloepithelioma in a 3
      year old girl. She presented symptoms of increased intracranial pressure. On
      examination, she had coordination problems, ptosis and exotropia of the right
      eye. Magnetic resonance imaging demonstrated a large cerebellar vermix tumor.
      Immuno-histochemistry revealed a diffuse positivity for Vimentin and focal
      positivity for the epithelial membrane antigen, but Glial Fibrillary Acidic
      Protein and Synaptophysin were negative, the MIB-1 antibody was very high. She
      received postoperative craniospinal irradiation and died 7 months later.
      Conclusion: We describe the features (epidemiological, clinical, histological,
      immunohistochemical and therapeutic outcomes) of our case and confront it to
      literature data.

PMID- 29200960
TI  - Solitary fibrous tumor occurring in the parotid gland: a case report.
AB  - Background: Solitary fibrous tumor is an uncommon spindle cell neoplasm of
      unknown origin. It has been reported in many anatomic sites, with a rare
      occurrence in the head and neck region. Solitary fibrous tumors of the parotid
      gland are exceptional; their clinical and radiologic features are non specific,
      often mimicking more common salivary gland tumors. Pathologic examination and
      immunohistochemistry are required to make the correct diagnosis. The prognosis is
      favorable, with most tumors being benign, and complete surgical resection is the
      treatment of choice. Case presentation: We report the case of a 42-year-old man
      who presented with a painless mass involving the parotid gland. A parotidectomy
      was performed, and follow up was unremarkable. Gross examination showed a well
      circumscribed, firm tumor measuring 3,4 cm. Histologically, the tumor was
      composed of a spindle cell proliferation of variable cellularity, with staghorn
      vessels. A panel of immunohistochemical stains was performed, and confirmed the
      diagnosis of parotid gland solitary fibrous tumor. Conclusion: In this report we
      aim to increase awareness of this rare entity among clinicians and pathologists,
      and to emphasize the role of immunohistochemistry in confirming the diagnosis.

PMID- 29200962
TI  - Measuring nurses' perception of work environment: a scoping review of
      questionnaires.
AB  - Background: Nurses' work environment has been shown to be associated with quality
      of care and organizational outcomes. In order to monitor the work environment, it
      is useful for all stakeholders to know the questionnaires that assess or evaluate
      conditions for delivering nursing care. The aim of this article is: to review the
      literature for assessed survey questionnaires that measure nurses' perception of
      their work environment, make a brief assessment, and map the content domains
      included in a selection of questionnaires. Methods: The search included
      electronic databases of internationally published literature, international
      websites, and hand searches of reference lists. Eligible papers describing a
      questionnaire had to be; a) suitable for nurses working in direct care in general
      hospitals, nursing homes or home healthcare settings; and b) constructed to
      measure work environment characteristics that are amenable to change and related
      to patient and organizational outcomes; and c) presented along with an assessment
      of their measurement properties. Results: The search yielded 5077 unique
      articles. For the final synthesis, 65 articles met inclusion criteria, consisting
      of 34 questionnaires measuring nursing work environments in different settings.
      Most of the questionnaires that we found were developed, and tested, for
      registered nurses in a general hospital setting. Six questionnaires were
      developed specifically for use in nursing home settings and one for home
      healthcare. The content domains covered by the questionnaires were both
      overlapping and unique and the terminology in use was inconsistent. The most
      common content domains in the work environment questionnaires were supportive
      managers, collaborative relationships with peers, busyness, professional practice
      and autonomy. Conclusions: The findings from this review enhance the
      understanding of how "work environment" can be measured by an overview of
      existing questionnaires and domains. Our results indicate that there are very
      many work environment questionnaires with varying content.

PMID- 29200963
TI  - Mobility care in nursing homes: development and psychometric evaluation of the
      kinaesthetics competence self-evaluation (KCSE) scale.
AB  - Background: Impaired mobility is a prevalent condition among care-dependent
      persons living in nursing homes. Therefore, competence development of nursing
      staff in mobility care is important. This study aimed to develop and initially
      test the Kinaesthetics Competence Self-Evaluation (KCSE) scale for assessing
      nursing staff's competence in mobility care. Methods: The KCSE scale was
      developed based on an analysis of the concept of nurses' competence in
      kinaesthetics. Kinaesthetics is a training concept that provides theory and
      practice about movement foundations that comprise activities of daily living. The
      scale contains 28 items and four subscales (attitude, dynamic state, knowledge
      and skills). Content validity was assessed by determining the content validity
      index within two expert panels. Internal consistency and construct validity were
      tested within a cross-sectional study in three nursing homes in the German
      speaking region of Switzerland between September and November 2015. Results: The
      content validity index for the entire scale was good (0.93). Based on a sample of
      nursing staff (n = 180) the internal consistency results were good for the whole
      scale (Cronbach's alpha = 0.91) and for the subscales knowledge and skills (alpha
      = 0.91, 0.86), acceptable for the subscale attitude (alpha = 0.63) and weak for
      the subscale dynamic state (alpha = 0.54). Most items showed acceptable inter
      item and item-total correlations. Based on the exploratory factor analysis, four
      factors explaining 52% of the variance were extracted. Conclusion: The newly
      developed KCSE scale is a promising instrument for measuring nursing staff's
      attitude, dynamic state, knowledge, and skills in mobility care based on
      kinaesthetics. Despite the need for further psychometric evaluation, the KCSE
      scale can be used in clinical practice to evaluate competence in mobility care
      based on kinaesthetics and to identify educational needs for nursing staff.

PMID- 29200964
TI  - Burden of musculoskeletal disorders among registered nurses: evidence from the
      Thai nurse cohort study.
AB  - Background: Musculoskeletal disorders (MSDs) are a major public health problem
      among registered nurses (RNs) in Thailand. Information on their burdens at a
      national level is limited. This study estimated the prevalence of MSDs among RNs
      using the 2009 Thai Nurse Cohort, a nationally representative sample of RNs in
      Thailand. Methods: This study is part of the first wave survey of the Thai Nurse
      Cohort Study (TNCS) conducted in 2009. Members of the cohort consisted of 18,756
      RNs across Thailand. A 13-page self-administered questionnaire was sent to
      participants where MSDs were measured by self-reported answers to questions
      related to experiencing MSDs during a previous year. However, 1070 RNs were
      excluded from this study since they were unemployed during a previous year,
      therefore the final sample size was 17,686 RNs. A 12-month prevalence of MSDs and
      its 95% confidence interval (95% CI) were estimated based on normal approximation
      to binomial distribution. Chi-square test for trend was used. Results: Of the
      17,686 RNs, 47.8% (95% CI: 47.0-48.5) reported having MSDs during the previous 12
      months. The prevalence of MSDs significantly increased with age, body mass index,
      and working duration (all P < 0.001). Compared to the non-MSD group, RNs with
      MSDs had a higher proportion who perceived MSDs as a long-term, chronic medical
      condition (78.1% vs 20.7%; p < 0.001), being currently on medication (49.4% vs
      14.7%; p < 0.001), using pain relief medication almost every day (9.0% vs 1.9%; p
      < 0.001), experiencing sickness absence (15.7% vs 1.1%; p < 0.001), seeking
      medical specialist consultations (odds ratio, OR 2.2; 95% CI: 2.0-2.3; p <
      0.001), and seeking alternative medications (OR 2.5; 95% CI: 2.3-2.7; p < 0.001).
      Conclusions: Musculoskeletal disorders affected almost half of the RNs in
      Thailand annually. They placed a major healthcare burden and were a major cause
      of working days lost due to sick leaves, diminished productivity and quality of
      patient care. More attention should be paid to the prevention and effective
      management of MSDs in RNs in Thailand. Further study on ergonomics related to
      MSDs and its prevention are needed.

PMID- 29200965
TI  - Patient preferences for participation in patient care and safety activities in
      hospitals.
AB  - Background: Active patient participation is a patient safety priority for health
      care. Yet, patients and their preferences are less understood. The aim of the
      study was to explore hospitalised patients' preferences on participation in their
      care and safety activities in Sweden. Methods: Exploratory qualitative study.
      Data were collected over a four-month period in 2013 and 2014. Semi-structured
      interviews were conducted with 20 patients who were admitted to one of four
      medical wards at a university hospital in Sweden. Data were analysed using
      thematic analysis. Results: Nine men and eleven women, whose median age was 72
      years (range 22-89), were included in the study. Five themes emerged with the
      thematic analysis: endorsing participation; understanding enables participation;
      enacting patient safety by participation; impediments to participation; and the
      significance of participation. This study demonstrated that patients wanted to be
      active participants in their care and safety activities by having a voice and
      being a part of the decision-making process, sharing information and possessing
      knowledge about their conditions. These factors were all enablers for patient
      participation. However, a number of barriers hampered participation, such as
      power imbalances, lack of patient acuity and patient uncertainty. Patients'
      participation in care and patient safety activities seemed to determine whether
      patients were feeling safe or ignored. Conclusion: This study contributes to the
      existing literature with fundamental evidence of patients' willingness to
      participate in care and safety activities. Promoting patient participation begins
      by understanding the patients' unique preferences and needs for care,
      establishing a good relationship and paying attention to each patient's ability
      to participate despite their illness.

PMID- 29200966
TI  - Microencapsulation of low-passage poorly-differentiated human mucoepidermoid
      carcinoma cells by alginate microcapsules: in vitro profiling of angiogenesis
      related molecules.
AB  - Background: Human mucoepidermoid carcinoma (MEC) is regarded as the most common
      primary salivary malignancy. High-grade MEC has a high risk of recurrence and
      poor prognosis. Tumor angiogenesis, induced by poorly differentiated cancer cells
      of high-grade MEC, contributes to tumor growth and metastasis. Therefore,
      elucidating molecular mechanisms underlying the pro-angiogenic ability of poorly
      differentiated MEC cells is critical for the understanding of high-grade MEC
      progression. It is well known that three-dimensional (3D) cell culture, in
      contrast with conventional two-dimensional (2D) culture, provides a better
      approach to in vitro recapitulation of in vivo characteristics of cancer cells
      and their surrounding microenvironment. The purpose of this study was to model a
      3D environment for in vitro gene expression profiling of key molecules in poorly
      differentiated MEC cells for cancer neovascularization and compared them with
      traditional 2D cell culture. Methods: Low-passage poorly differentiated MEC
      cells, derived from human patient samples of high-grade MEC, were
      microencapsulated in sodium alginate gel microcapsules (3D culture) and compared
      with cells grown in 2D culture. Cancer cell proliferation was determined by MTT
      assays for 1 week, and gene expression of VEGF-A, bFGF and TSP-1 was analyzed by
      western blotting or ELISA. The hypoxic environment in 3D versus 2D culture were
      assessed by western blotting or immunofluorescence for HIF1alpha, and the effect
      of hypoxia on VEGF-A gene expression in 3D cultured cancer cells was assessed by
      western blotting with the use of the HIF1alpha inhibitor, 2-methoxyestradiol (2
      MeOE2). Results: When encapsulated in alginate gel microcapsules, low-passage
      poorly differentiated human MEC cells grew in blocks and demonstrated stronger
      and relatively unlimited proliferation activities. Moreover, significant
      differences were found in gene expression, with 3D-grown cancer cells a
      significant increment of VEGF-A and bFGF and a drastic reduction of TSP-1.
      Consistently, 3D-grown cancer cells secreted significantly more VEGF-A than 2D
      culture cancer cells. Furthermore, 3D-grown cancer cells showed significantly
      higher expression of HIF1alpha, a molecular indicator of hypoxia; the increased
      expression of VEGF-A in 3D cultured cancer cells was shown to be dependent on the
      HIF1alpha activities. Conclusions: The present work shows the effects of 3D
      culture model by alginate microencapsulation on the proangiogenic potentials of
      low-passage poorly differentiated human MEC cells. Cancer cells in this 3D system
      demonstrate significant intensification of key molecular processes for tumor
      angiogenesis. This is due to a better modeling of the hypoxic tumor
      microenvironment during 3D culture.

PMID- 29200967
TI  - Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck
      squamous cell carcinoma.
AB  - Background: Bmi1 (B lymphoma Mo-MLV insertion region 1 homolog) contributes to
      human tumorigenesis via epigenetic transcriptional silencing and represents a
      novel therapeutic target with great potentials. Here we sought to determine the
      therapeutic efficiency of PTC-209, a potent and selective Bmi1 inhibitor, in head
      neck squamous cell carcinoma (HNSCC) cells and a HNSCC xenograft model. Methods:
      The mutation pattern, mRNA level of Bmi1 in HNSCC and its associations with
      clinicopathological parameters were determined through comprehensive data mining
      and interrogation using publicly available databases GENT, cBioPortal, Oncomine
      and TCGA. The PTC-209, a selective and potent Bmi1 inhibitor, was exploited and
      its effect on Bmi1 expression was measured in two HNSCC cell lines Cal27 and
      FaDu. The phenotypical changes of HNSCC cells were observed upon PTC-209
      treatment in vitro. Moreover, the therapeutic effects of PTC-209 for HNSCC were
      determined in a xenograft animal model. Results: Through comprehensive data
      mining and interrogation, we found that Bmi1 mRNA was frequently overexpressed in
      a subset of HNSCC samples. Our data revealed that PTC-209 robustly reduced the
      expression of Bmi1 in Cal27 and FaDu cells presumably by post-transcriptional
      repression and ubiquitin-proteasomal degradation. PTC-209 treatment resulted in
      impaired cell proliferation, G1-phase cell cycle arrest, compromised migration
      and invasiveness, and increased cell apoptosis and chemosensitivity to 5-FU and
      cisplatin in vitro. Moreover, PTC-209 exposure reduced colony formation,
      tumorsphere formation and the percentage of ALDH1+ subpopulation in both Cal27
      and FaDu cells. Importantly, in vivo PTC-209 administration significantly reduced
      tumor growth in a HNSCC xenograft model probably by Bmi1 inhibition and impaired
      cell proliferation. Conclusions: Our findings indicate that pharmacological
      inhibition of Bmi1 is a novel therapeutic strategy for HNSCC patients, especially
      with those with aberrant Bmi1 overexpression.

PMID- 29200968
TI  - Volatile organic metabolites identify patients with gastric carcinoma, gastric
      ulcer, or gastritis and control patients.
AB  - Background: Gastric cancer ranks 4th among the most common cancers worldwide, and
      the mortality caused by gastric cancer is 2nd only to lung cancer. Gastric cancer
      shows a lack of specific symptoms in its early stages. In addition, its clinical
      symptoms often do not match the corresponding stage. Upper gastrointestinal
      endoscopy with biopsy is the gold standard for the diagnosis of gastric cancer
      because of its high accuracy. However, this operation is invasive, patient
      compliance is poor, and high demands for medical staff and equipment are typical
      of this procedure. Recent studies have demonstrated a connection between specific
      breath volatile organic compounds (VOCs) and various forms of cancers. Methods:
      We collected expired air from patients with gastric cancer, chronic atrophic
      gastritis or gastric ulcers as well as from healthy individuals. Solid-phase
      microextraction, gas chromatography-mass spectrometry and principal component
      analysis statistics were applied to identify potential biomarkers of gastric
      cancer among VOCs. Results: Fourteen differential metabolites were annotated
      using the NIST 11 database, with a similarity threshold of 70%. Currently, the
      metabolic origin of VOCs remains unclear; however, several pathways might explain
      the decreasing or increasing trends that were observed. Conclusions: The results
      of this study demonstrate the existence of specific VOC profiles associated with
      patients with carcinoma. In addition, these metabolites may contribute to the
      diagnosis and screening of patients with carcinoma.

PMID- 29200969
TI  - Inhibition of breast cancer cell proliferation and tumorigenesis by long non
      coding RNA RPPH1 down-regulation of miR-122 expression.
AB  - Background: Recent studies showed that long non-coding RNA (lncRNA) plays an
      important role in many life activities. RPPH1 is one of the lncRNA genes that are
      expressed differently between breast cancer and normal tissues by the lncRNA gene
      chip. Our study was conducted to examine the regulation of lncRNA RPPH1 in breast
      cancer. Methods: Two cell lines, MCF-7 and MDA-MB-231, were selected to be the
      research objects in this study; RPPH1 overexpression and knockdown models were
      established by transforming vectors. Real-time polymerase chain reaction, MTT
      assay, clone formation and cell flow cytometer assay were used to test the
      function of RPPH1. Dual-luciferase assay was used to detect a target relationship
      between RPPH1 and miR-122. Results: RPPH1 overexpression promoted cell cycle and
      proliferation and increased colony formation. In the RPPH1 overexpression model,
      there was a target relationship between RPPH1 and miR-122, and some of the
      downstream genes of miR-122, including ADAM10, PKM2, NOD2 and IGF1R, were
      increased. Moreover, we found that lentivirus-mediated interference of lncRNA
      RPPH1 inhibited tumour growth in nude mice. Conclusion: Breast cancer progression
      can be promoted by directly targeting miR-122 through lncRNA RPPH1. This study
      provided evidence that can serve as the molecular basis for improving treatment
      options for patients.

PMID- 29200970
TI  - Systematic review of randomized controlled trials in the treatment of dry eye
      disease in Sjogren syndrome.
AB  - Primary Sjogren's syndrome is an autoimmune disease characterized by dry eye and
      dry mouth. We systematically reviewed all the randomized controlled clinical
      trials published in the last 15 years that included ocular outcomes. We found 22
      trials involving 9 topical, 10 oral, 2 intravenous and 1 subcutaneous modalities
      of treatment. Fluoromethalone eye drops over 8 weeks were more effective than
      topical cyclosporine in the treatment of dry eye symptoms and signs; similarly,
      indomethacin eye drops over 1 month were more efficacious than diclofenac eye
      drops. Oral pilocarpine 5 mg twice daily over 3 months was superior to use of
      lubricants or punctal plugs for treating dry eye, but 5% of participants had
      gastrointestinal adverse effects from pilocarpine, though none discontinued
      treatment. In contrast, etanercept, a TNF-alpha blocking antibody, administered
      as subcutaneous injections twice weekly, did not improve dry eye significantly
      compared to placebo injections. In conclusion, topical corticosteroids have been
      shown to be effective in dry eye associated with Sjogren's syndrome. As some
      topical non-steroidal anti-inflammatory drugs may be more effective than others,
      these should be further evaluated. Systemic secretagogues like pilocarpine have a
      role in Sjogren's syndrome but the adverse effects may limit their clinical use.
      It is disappointing that systemic cytokine therapy did not produce encouraging
      ocular outcomes but participants should have assessment of cytokine levels in
      such trials, as those with higher baseline cytokine levels may respond better.
      (229 words).

PMID- 29200971
TI  - vWF/ADAMTS13 is associated with on-aspirin residual platelet reactivity and
      clinical outcome in patients with stable coronary artery disease.
AB  - Background: The mechanisms behind residual platelet reactivity (RPR) despite
      aspirin treatment are not established. It has been shown that coronary artery
      disease (CAD) patients with high on-aspirin RPR have elevated levels of von
      Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large vWF
      multimers into less active fragments.Our aim was to investigate whether ADAMTS13
      and vWF/ADAMTS13 ratio were associated with high RPR, and further with clinical
      endpoints after 2 years. Methods: Stable aspirin-treated CAD patients (n = 999)
      from the ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity
      were analysed using chromogenic assays. Endpoints were a composite of acute
      myocardial infarction, stroke and death. Results: The number of patients with
      high RPR was 258 (25.8%). Their serum thromboxane B2 (TxB2) levels were low,
      indicating inhibition of COX-1. They had significantly lower levels of ADAMTS13
      antigen compared to patients with low RPR (517 vs 544 ng/mL, p = 0.001) and
      significantly lower ADAMTS13 activity (0.99 vs 1.04 IU/mL, p = 0.020). The
      differences were more pronounced when relating RPR to ratios of vWF/ADAMTS13
      antigen and vWF/ADAMTS13 activity (p < 0.001, both). We found an inverse
      correlation between vWF and ADAMTS13 antigen (r = -0.14, p < 0.001) and ADAMTS13
      activity (r = -0.11, p < 0.001). No correlations between TxB2 and ADAMTS13
      antigen or activity, were observed, implying that ADAMTS13 is not involved in
      TxB2 production. Patients who experienced endpoints (n = 73) had higher vWF level
      (113 vs 105%, p = 0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20, p = 0.012)
      compared to patients without. When dichotomizing vWF/ADAMTS13 antigen at median
      level we observed that patients above median had higher risk for suffering
      endpoints, with an adjusted OR of 1.86 (95% CI 1.45, 2.82). Conclusion: These
      results indicate that ADAMTS13 is of importance for RPR, and that it in
      combination with vWF also is associated with clinical endpoints in stable CAD
      patients on aspirin. Trial registration: Clinicaltrials.gov NCT00222261.
      Registered 13.09.2005. Retrospectively registered.

PMID- 29200972
TI  - Problems and Service Needs Among Ex-Offenders with HIV Risk Behaviors Entering
      Sober Living Recovery Homes.
AB  - There is currently a nationwide effort to decrease the number of persons who are
      incarcerated in jails and prisons. However, many ex-offenders on probation or
      parole do not have access to affordable housing and larger proportions have
      histories of HIV risk as well as substance abuse problems. In California, sober
      living houses (SLHs) are becoming an increasingly popular housing option for
      these individuals. Based largely on the principles of Alcoholics Anonymous (AA),
      SLHs require abstinence from alcohol and drugs and provide peer support for
      recovery. The current study examined the types of problems experienced among 330
      ex-offenders with lifetime risk for HIV during the six months prior to entering
      SLHs. Nearly three fourths (74%) of all ex-offenders entering the houses had at
      least one HIV risk. The importance of housing was evident in the finding that
      housing status and participants' perceptions of their housing situation were
      associated with a variety of problem areas, including substance use, HIV risk,
      psychiatric severity, and legal problems. SLHs represent an important housing
      option for ex-offenders, but many residents may need additional services to
      address various problems.

PMID- 29200973
TI  - Prehabilitation and Nutritional Support to Improve Perioperative Outcomes.
AB  - Purpose of Review: The purpose of this study is to evaluate the role of physical
      exercise and nutrition interventions in adult patients before elective major
      surgery. Recent Findings: Exercise training before elective adult major surgery
      is feasible, safe, and efficacious, but the clinical effectiveness remains
      uncertain. Early data suggests a reduction in morbidity, length of stay, and
      quality of life, but the results of larger definitive studies are awaited.
      Nutritional interventions are less well evaluated and when they are, it is often
      in combination with exercise interventions as part of a prehabilitation package.
      Summary: Studies evaluating exercise and nutrition interventions before elective
      major surgery in adults are producing encouraging early results, but definitive
      clinical evidence is currently very limited. Future research should focus on
      refining interventions, exploring mechanism, and evaluating the interactions
      between therapies and large-scale clinical effectiveness studies.

PMID- 29200974
TI  - Stroke Volume Monitoring: Novel Continuous Wave Doppler Parameters, Algorithms
      and Advanced Noninvasive Haemodynamic Concepts.
AB  - Purpose of Review: Adequate oxygen delivery is essential for life, with hypoxia
      resulting in dysfunction, and ultimately death, of the cells, organs and
      organism. Blood flow delivers the oxygen bound in the blood, while haemodynamics
      is the science of blood flow. Stroke volume (SV) is the fundamental unit of blood
      flow, and reflects the interdependent performance of the heart, the vessels and
      the autonomic nervous system. However, haemodynamic management remains generally
      poor and predominantly guided by simple blood pressure observations alone. Recent
      Findings: Doppler ultrasound measures SV with unequalled clinical precision when
      operated by trained personnel. Combining SV with BP measurements allows
      calculation of flow-pressure based measures which better reflect cardiovascular
      performance and allows personalised physiologic and pathophysiologic modelling
      consistent with Frank's and Starling's observations. Summary: Doppler SV
      monitoring and novel flow-pressure parameters may improve our understanding of
      the cardiovascular system and lead to improved diagnosis and therapy. This review
      examines the physics and practice of Doppler SV monitoring and its application in
      advanced haemodynamics.

PMID- 29200975
TI  - Cardiac Output Monitoring: Validation Studies-how Results Should be Presented.
AB  - Purpose of Review: Cardiac output monitors can be assessed by a variety of
      techniques, but a common principle is quantifying agreement between a reference
      standard and new monitor. The current standard analysis technique is a Bland
      Altman plot. The Bland-Altman plot evaluates bias between mean differences of
      cardiac output, from which an agreement interval is derived. These limits are,
      however, statistical limits of agreement and the clinical acceptability will
      depend upon context and application. This article provides suggestions for
      understanding and presenting the results of cardiac output validation, using
      standard metrology alongside proposals for criteria used to accept new
      techniques. Recent Findings: Confusion about the appropriate way to report
      "precision" in method comparison studies stem from a lack of clarity on how
      single or repeated measurements should be interpreted. During serial measurements
      of cardiac output the true value changes, thus measurement should be considered
      as serial rather than repeated. Method agreement based upon precision achieved by
      cardiac output monitors needs to consider each method's general variability
      around true values obtained and this data should be generated and presented as
      part of each study design. Summary: Studies should report serial measurements
      from two techniques for cardiac output monitoring. Results of similar techniques
      from other studies may not always be transferred and compared. Bias and intervals
      of agreement should be presented as Bland-Altman plots with dynamic cardiac
      output trends in polar plots. Percentage error should be calculated to allow
      appropriate comparison of techniques for study populations with different
      expected cardiac output values.

PMID- 29200976
TI  - Improvement Science in Anaesthesia.
AB  - Purpose of Review: This article offers an overview of the history and features of
      Improvement Science in general and some of its applications to Anaesthesia in
      particular. Recent Findings: Improvement Science is an evolving discipline aiming
      to generate learning from quality improvement interventions. An increasingly
      common approach to improving Anaesthesia services is to employ large-scale
      perioperative data measurement and feedback programmes. Improvement Science
      offers important insights on questions such as which indicators to collect data
      for; how to capture that data; how it can be presented in engaging visual
      formats; how it could/should be fed back to frontline staff and how they can be
      supported in their use of data to generate improvement. Summary: Data measurement
      and feedback systems represent opportunities for anaesthetists to work with
      multidisciplinary colleagues to help improve services and outcomes for surgical
      patients. Improvement Science can help evaluate which approaches work, and in
      which contexts, and is therefore of value to healthcare commissioners, providers
      and patients.

PMID- 29200977
TI  - Clinical Trial Design as a Decision Problem.
AB  - The intent of this discussion is to highlight opportunities and limitations of
      utility-based and decision theoretic arguments in clinical trial design. The
      discussion is based on a specific case study, but the arguments and principles
      remain valid in general. The example concerns the design of a randomized clinical
      trial to compare a gel sealant versus standard care for resolving air leaks after
      pulmonary resection. The design follows a principled approach to optimal decision
      making, including a probability model for the unknown distributions of time to
      resolution of air leaks under the two treatment arms, and an explicit utility
      function that quantifies clinical preferences for alternative outcomes. As is
      typical for any real application, the final implementation includes some
      compromises from the initial principled setup. In particular, we use the formal
      decision problem only for the final decision, but use reasonable ad-hoc decision
      boundaries for making interim group sequential decisions that stop the trial
      early. Beyond the discussion of the particular study, we review more general
      considerations of using a decision theoretic approach for clinical trial design
      and summarize some of the reasons why such approaches are not commonly used.

PMID- 29200978
TI  - Case 1: A term infant with apnea and stiffening.

PMID- 29200979
TI  - The Association between Compassionate Goals and Relational-Interdependent Self
      Construal.
AB  - Although research has examined the consequences of relational self-construal,
      little is known about what psychological factors predict it. Four studies
      examined the association between compassionate goals and relational self
      construal. Study 1 showed that compassionate goals are positively associated with
      relational self-construal in college students. Study 2 replicated this
      association among adults in romantic relationships. Studies 3 and 4 showed that
      compassionate goals predict increased relational self-construals over time in
      college roommates. Moreover, Studies 2-4 showed that responsiveness to
      relationship partners statistically mediated the association between
      compassionate goals and self-construal. These studies suggested that people with
      compassionate goals have highly relational self-construals and that they also
      develop higher levels of relational self-construals by being responsive to
      relationship partners.

PMID- 29200980
TI  - Locally Advanced Disease and Pelvic Exenterations.
AB  - Advanced primary and recurrent colorectal cancer can be successfully treated by
      experienced, dedicated centers delivering good outcomes with low mortality and
      morbidity. Development and implementation of a comprehensive referral pathway is
      to be encouraged. Multidisciplinary team management is essential in the
      management of this complex group of patients and is associated with significantly
      more complete preoperative evaluation and more accurate provision of patient
      information, as well as improved access to the most appropriate individualized
      management plan. A structured selection process can improve outcomes through
      standardized approaches to service delivery to provide the highest quality of
      care.

PMID- 29200981
TI  - Semantic Specificity in One-Year-Olds' Word Comprehension.
AB  - The present study investigated infants' knowledge about familiar nouns. Infants
      (n = 46, 12-20-month-olds) saw two-image displays of familiar objects, or one
      familiar and one novel object. Infants heard either a matching word (e.g. "foot'
      when seeing foot and juice), a related word (e.g. "sock" when seeing foot and
      juice) or a nonce word (e.g. "fep" when seeing a novel object and dog). Across
      the whole sample, infants reliably fixated the referent on matching and nonce
      trials. On the critical related trials we found increasingly less looking to the
      incorrect (but related) image with age. These results suggest that one-year-olds
      look at familiar objects both when they hear them labeled and when they hear
      related labels, to similar degrees, but over the second year increasingly rely on
      semantic fit. We suggest that infants' initial semantic representations are
      imprecise, and continue to sharpen over the second postnatal year.

PMID- 29200982
TI  - Native whey protein with high levels of leucine results in similar post-exercise
      muscular anabolic responses as regular whey protein: a randomized controlled
      trial.
AB  - Background: Protein intake is essential to maximally stimulate muscle protein
      synthesis, and the amino acid leucine seems to possess a superior effect on
      muscle protein synthesis compared to other amino acids. Native whey has higher
      leucine content and thus a potentially greater anabolic effect on muscle than
      regular whey (WPC-80). This study compared the acute anabolic effects of
      ingesting 2 * 20 g of native whey protein, WPC-80 or milk protein after a
      resistance exercise session. Methods: A total of 24 young resistance trained men
      and women took part in this double blind, randomized, partial crossover,
      controlled study. Participants received either WPC-80 and native whey (n = 10),
      in a crossover design, or milk (n = 12). Supplements were ingested immediately
      (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance
      exercise. Blood samples and muscle biopsies were collected to measure plasma
      concentrations of amino acids by gas-chromatography mass spectrometry, muscle
      phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting, and mixed muscle
      protein synthesis by use of [2H5]phenylalanine-infusion, gas-chromatography mass
      spectrometry and isotope-ratio mass spectrometry. Being the main comparison,
      differences between native whey and WPC-80 were analysed by a one-way ANOVA and
      comparisons between the whey supplements and milk were analysed by a two-way
      ANOVA. Results: Native whey increased blood leucine concentrations more than WPC
      80 and milk (P < 0.05). Native whey ingestion induced a greater phosphorylation
      of p70S6K than milk 180 min after exercise (P = 0.03). Muscle protein synthesis
      rates increased 1-3 h hours after exercise with WPC-80 (0.119%), and 1-5 h after
      exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1
      5 h after exercise with native whey than with milk (0.112% vs. 0.064, P = 0.023).
      Conclusions: Despite higher-magnitude increases in blood leucine concentrations
      with native whey, it was not superior to WPC-80 concerning effect on muscle
      protein synthesis and phosphorylation of p70S6K during a 5-h post-exercise
      period. Native whey increased phosphorylation of p70S6K and muscle protein
      synthesis rates to a greater extent than milk during the 5-h post exercise
      period. Trial registration: This study was retrospectively registered at
      clinicaltrials.gov as NCT02968888.

PMID- 29200983
TI  - The short-term effect of high versus moderate protein intake on recovery after
      strength training in resistance-trained individuals.
AB  - Background: Dietary protein intakes up to 2.9 g.kg-1.d-1 and protein consumption
      before and after resistance training may enhance recovery, resulting in
      hypertrophy and strength gains. However, it remains unclear whether protein
      quantity or nutrient timing is central to positive adaptations. This study
      investigated the effect of total dietary protein content, whilst controlling for
      protein timing, on recovery in resistance trainees. Methods: Fourteen resistance
      trained individuals underwent two 10-day isocaloric dietary regimes with a
      protein content of 1.8 g.kg-1.d-1 (PROMOD) or 2.9 g.kg-1.d-1 (PROHIGH) in a
      randomised, counterbalanced, crossover design. On days 8-10 (T1-T3), participants
      undertook resistance exercise under controlled conditions, performing 3 sets of
      squat, bench press and bent-over rows at 80% 1 repetition maximum until
      volitional exhaustion. Additionally, participants consumed a 0.4 g.kg-1 whey
      protein concentrate/isolate mix 30 min before and after exercise sessions to
      standardise protein timing specific to training. Recovery was assessed via daily
      repetition performance, muscle soreness, bioelectrical impedance phase angle,
      plasma creatine kinase (CK) and tumor necrosis factor-alpha (TNF-alpha). Results:
      No significant differences were reported between conditions for any of the
      performance repetition count variables (p > 0.05). However, within PROMOD only,
      squat performance total repetition count was significantly lower at T3 (19.7 +/-
      6.8) compared to T1 (23.0 +/- 7.5; p = 0.006). Pre and post-exercise CK
      concentrations significantly increased across test days (p <= 0.003), although no
      differences were reported between conditions. No differences for TNF-alpha or
      muscle soreness were reported between dietary conditions. Phase angle was
      significantly greater at T3 for PROHIGH (8.26 +/- 0.82 degrees ) compared with
      PROMOD (8.08 +/- 0.80 degrees ; p = 0.012). Conclusions: When energy intake and
      peri-exercise protein intake was controlled for, a short term PROHIGH diet did
      not improve markers of muscle damage or soreness in comparison to a PROMOD
      approach following repeated days of intensive training. Whilst it is therefore
      likely that moderate protein intakes (1.8 g.kg-1.d-1) may be sufficient for
      resistance-trained individuals, it is noteworthy that both lower body exercise
      performance and bioelectrical phase angle were maintained with PROHIGH. Longer
      term interventions are warranted to determine whether PROMOD intakes are
      sufficient during prolonged training periods or when extensive exercise (e.g.
      training twice daily) is undertaken.

PMID- 29200984
TI  - Mouth rinsing with a carbohydrate solution attenuates exercise-induced decline in
      executive function.
AB  - Background: A decline in executive function could have a negative influence on
      the control of actions in dynamic situations, such as sports activities. Mouth
      rinsing with a carbohydrate solution could serve as an effective treatment for
      preserving the executive function in exercise. The purpose of this study was to
      examine the effects of mouth rinsing with a carbohydrate solution on executive
      function after sustained moderately high-intensity exercise. Methods: Eight young
      healthy participants completed 65 min of running at 75% VO2max with two mouth
      rinsing conditions: with a carbohydrate solution (CHO) or with water (CON).
      Executive function was assessed before and after exercise by using the
      incongruent task of the Stroop Color and Word Test. The levels of blood glucose;
      and plasma adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine
      (NE) were evaluated. A two-way repeated-measures ANOVA, with condition (CHO and
      CON) and time (pre-exercise and post-exercise) as factors, was used to examine
      the main and interaction effects on the outcome measures. Results: The reaction
      time in the incongruent condition of the Stroop test significantly increased
      after exercise in CON (pre-exercise 529 +/- 45 ms vs. post-exercise 547 +/- 60
      ms, P = 0.029) but not in CHO (pre-exercise 531 +/- 54 ms vs. post-exercise 522
      +/- 80 ms), which resulted in a significant interaction (condition * time) on the
      reaction time (P = 0.028). The increased reaction time in CON indicates a decline
      in the executive function, which was attenuated in CHO. Increases in plasma
      epinephrine and NE levels demonstrated a trend toward attenuation accompanying
      CHO (P < 0.085), which appeared to be associated with the preservation of
      executive function. The blood glucose concentration showed neither significant
      interactions nor main effects of condition. Conclusions: These findings indicate
      that mouth rinsing with a carbohydrate solution attenuated the decline in
      executive function induced by sustained moderately high-intensity exercise, and
      that such attenuation seems to be unrelated to carbohydrate metabolic pathway but
      rather attributed, in part, to the inhibition of the excessive release of stress
      hormones.

PMID- 29200985
TI  - The Impact of Punitive Immigrant Laws on the Health of Latina/o Populations.
AB  - This study examines how anti-immigrant policies affect the physical health of
      Latina/os in the United States. Merging two unique datasets: sum of anti
      immigrant policies by state from 2005-2011 and a 2011 Robert Wood Johnson Center
      for Health Policy nationally representative sample of Latina/os (n=1,200), we
      estimate a series of logistic regressions to understand how anti-immigrant
      legislations are affecting the health of Latina/os. Our modeling approach takes
      into consideration Latinos' diverse experience, context that is widely overlooked
      in datasets that treat Latina/os as a homogeneous ethnic group. Our findings
      suggest that an increase in anti-immigrant laws enacted by a state decreases the
      probability of respondents reporting optimal health, even when controlling for
      other relevant factors, such as citizenship status, language of interview, and
      interethnic variation. The implication and significance of this work has
      tremendous impacts for scholars, policy makers, health service providers and
      applied researchers interested in reducing health disparities among minority
      populations.

PMID- 29200986
TI  - Bidirectional Regulation of Mouse Embryonic Stem Cell Proliferation by Nicotine
      Is Mediated Through Wnt Signaling Pathway.
AB  - Introduction: Nicotine is a key biologically active compound of cigarettes.
      Although nicotine is a risk factor for various health issues, it may also be
      beneficial when treated at moderate concentrations. Nicotine has been shown to
      bidirectionally regulate stem cell proliferation and differentiation depending on
      the doses applied. It is not clear whether or how nicotine regulates mouse
      embryonic stem cell (mESC) survival and proliferation. Methods: Mouse embryonic
      stem cells were cultured in the presence of 0.01, 0.1, 1, or 10 MUM nicotine. The
      effects of nicotine on cell survival and proliferation were examined. The
      signaling pathway that mediated these effects was analyzed. Results: Cell
      viability was not affected by nicotine at all 4 concentrations examined. The
      proliferation of mESCs was promoted by 0.01 and 0.1 MUM nicotine and suppressed
      by 1 and 10 MUM. This dose-dependent regulation was mediated through the Wnt/beta
      catenin pathway. Modulation of Wnt/beta-catenin activity either worsens or
      reverses the effects of nicotine. Conclusions: We have identified a bidirectional
      function of nicotine on mESC proliferation through regulation of the Wnt/beta
      catenin pathway and this is associated with different doses. This study suggests
      that concentration of nicotine is a crucial aspect for consideration when
      designing research or therapeutic strategies.

PMID- 29200987
TI  - Bufadienolides of Kalanchoe species: an overview of chemical structure,
      biological activity and prospects for pharmacological use.
AB  - Toad venom is regarded as the main source of bufadienolides; however, synthesis
      of these substances takes also place in a variety of other animal and plant
      organisms, including ethnomedicinal plants of the Kalanchoe genus. Chemically,
      bufadienolides are a group of polyhydroxy C-24 steroids and their glycosides,
      containing a six-membered lactone (alpha-pyrone) ring at the C-17beta position.
      From the pharmacological point of view, bufadienolides might be a promising group
      of steroid hormones with cardioactive properties and anticancer activity. Most of
      the literature concerns bufadienolides of animal origin; however, the medicinal
      use of these compounds remains limited by their narrow therapeutic index and the
      risk of development of cardiotoxic effects. On the other hand, plants such as
      Kalanchoe are also a source of bufadienolides. Kalanchoe pinnata (life plant, air
      plant, cathedral bells), Kalanchoe daigremontiana (mother of thousands) and other
      Kalanchoe species are valuable herbs in traditional medicine of Asia and Africa.
      The present review focuses on the available data on chemical structures of 31
      compounds, biological properties and prospects for therapeutic use of
      bufadienolides from Kalanchoe species. Furthermore, it presents some new
      investigational trends in research on curative uses of these substances.

PMID- 29200989
TI  - Pushing the boundaries of laparoscopic myomectomy: a comparative analysis of peri
      operative outcomes in 323 women undergoing laparoscopic myomectomy in a tertiary
      referral centre.
AB  - Background: The aim of this study was to analyse the demographic data and peri
      operative outcomes of women undergoing a laparoscopic myomectomy and assess what
      factors, if any, precluded using the laparoscopic approach. Methods: A single
      surgeon observational study of 323 patients undergoing a laparoscopic myomectomy
      was undertaken. Data was collected prospectively over a 12-year period and
      analysed using SPSS. Surgical outcomes included operating time, estimated blood
      loss, conversion to laparotomy, intraoperative and postoperative complications
      and duration of inpatient stay. Results: A total of 323 patients underwent a
      laparoscopic myomectomy over the 12-year period. The majority of fibroids removed
      were intramural (49%) and subserosal (33%). The mean size of fibroids removed was
      7.66 +/- 2.83 (7.34-7.99) cm, and the mean number was 4 +/- 3.62 (3.6-4.39), with
      the greatest being 22 removed from a single patient. Average blood loss was
      279.14 +/- 221.10 (254.59-303.69) ml with mean duration of surgery and inpatient
      stay recorded as 112.92 +/- 43.21 (107.94-117.91) min and 1.88 +/- 0.95 (1.77
      1.99) days, respectively. No major intraoperative complications were noted, and
      the conversion to laparotomy rate was 0.62%. All histology following morcellation
      was benign. Over the 12-year period despite increasingly large and more numerous
      fibroids being tackled, increasing experience resulted in a simultaneous
      reduction in overall blood loss, operating time and duration of inpatient stay.
      Conclusions: Laparoscopic myomectomy is a safe and efficacious procedure that
      should be considered the gold standard surgical treatment option for fibroids.
      With experience, the procedure can be undertaken with minimal complications, a
      low risk of conversion to laparotomy and early discharge from hospital, even in
      cases of large and multiple fibroids that historically would have required the
      open approach. This allows even the most complex of cases to now benefit for the
      advantages of the minimal access approach.

PMID- 29200990
TI  - Intercepting the Gold-Catalysed Meyer-Schuster Rearrangement by Controlled
      Protodemetallation: A Regioselective Hydration of Propargylic Alcohols.
AB  - The regioselective gold-catalysed hydration of propargylic alcohols to beta
      hydroxy ketones can be achieved by diverting the gold-catalysed Meyer-Schuster
      rearrangement through the addition of a protic additive with a pKa of 7-9 such as
      p-nitrophenol, boric acid or a boronic acid. This provides an interesting
      alternative to an aldol reaction when combined with the straightforward addition
      of an alkyne to an aldehyde or ketone. The gold-catalysed reaction of an electron
      deficient, sterically hindered propargylic alcohol with a boronic acid led to the
      formation of an unusually stable cyclic boron enolate.

PMID- 29200991
TI  - Metal Organic Framework Crystals in Mixed-Matrix Membranes: Impact of the Filler
      Morphology on the Gas Separation Performance.
AB  - Mixed-matrix membranes (MMMs) comprising NH2-MIL-53(Al) and Matrimid(r) or 6FDA
      DAM have been investigated. The MOF loading has been varied between 5 and 20 wt%,
      while NH2-MIL-53(Al) with three different morphologies: nanoparticles, nanorods
      and microneedles have been dispersed in Matrimid(r). The synthesized membranes
      have been tested in the separation of CO2 from CH4 in an equimolar mixture. At 3
      bar and 298 K for 8 wt% MOF loading, incorporation of NH2-MIL-53(Al)
      nanoparticles leads to the largest improvement compared to nanorods and
      microneedles. The incorporation of the best performing filler, i.e. NH2-MIL
      53(Al) nanoparticles, to the highly permeable 6FDA-DAM has a larger effect, and
      the CO2 permeability increased up to 85 % with slightly lower selectivities for
      20 wt% MOF loading. Specifically, these membranes have a permeability of 660
      Barrer with CO2/CH4 separation factor of 28, leading to a performance very close
      to the Robeson limit of 2008. Furthermore, a new non-destructive technique based
      on Raman spectroscopy mapping is introduced to assess the homogeneity of the
      filler dispersion in the polymer matrix. The MOF contribution can be calculated
      by modelling the spectra. The determined homogeneity of the MOF filler
      distribution in the polymer is confirmed by FIB-SEM analysis.

PMID- 29200992
TI  - Pre-treated theaflavin-3,3'-digallate has a higher inhibitory effect on the
      HCT116 cell line.
AB  - The pro-apoptotic and inhibitory effects of the aflavin-3,3'-digallate (TFDG),
      which is the typical pigment in black tea, have been demonstrated in many cancer
      cell lines. However, TFDG is not stable in general culture conditions. So, to
      what extent TFDG or which degradation products of TFDG play an antitumor role is
      still unclear. In this study, we evaluated the effect of different treatments of
      TFDG on HCT116 cells. Compared with the control, both TFDG and O-TFDG (the TFDG
      that was pre-incubated in an incubator at 37 degrees C for 3 hbefore adding into
      96-well plates) significantly inhibited HCT116 cell growth. However, pre-treated
      TFDG was far better than TFDG. The IC50 values of TFDG and O-TFDG-3 were 17.26
      MUM and 8.98 MUM, respectively (the cells were treated by O-TFDG for only 3 h,
      after which the media were replaced by fresh media for another 69 h incubation).
      Cell-cycle analysis revealed that 20 MUM of O-TFDG and O-TFDG-3 caused cell-cycle
      arrest at G2 phase in HCT116 cells. Western blot analysis also demonstrated that
      the anti-inflammatory effect of O-TFDG-3 is stronger than that of TFDG by
      decreasing COX-2 and iNOS. On the other hand, O-TFDG induced HCT116 cells
      apoptosis mainly by increasing the expression of p53, p21, and cleaved caspase-3.
      The current study demonstrated that O-TFDG had a higher inhibitory effect on
      HCT116 cells than TFDG, and sowe may inferfromthis that the degradation products
      of TFDG play a key role against tumors.

PMID- 29200994
TI  - Spatio Temporal EEG Source Imaging with the Hierarchical Bayesian Elastic Net and
      Elitist Lasso Models.
AB  - The estimation of EEG generating sources constitutes an Inverse Problem (IP) in
      Neuroscience. This is an ill-posed problem due to the non-uniqueness of the
      solution and regularization or prior information is needed to undertake
      Electrophysiology Source Imaging. Structured Sparsity priors can be attained
      through combinations of (L1 norm-based) and (L2 norm-based) constraints such as
      the Elastic Net (ENET) and Elitist Lasso (ELASSO) models. The former model is
      used to find solutions with a small number of smooth nonzero patches, while the
      latter imposes different degrees of sparsity simultaneously along different
      dimensions of the spatio-temporal matrix solutions. Both models have been
      addressed within the penalized regression approach, where the regularization
      parameters are selected heuristically, leading usually to non-optimal and
      computationally expensive solutions. The existing Bayesian formulation of ENET
      allows hyperparameter learning, but using the computationally intensive Monte
      Carlo/Expectation Maximization methods, which makes impractical its application
      to the EEG IP. While the ELASSO have not been considered before into the Bayesian
      context. In this work, we attempt to solve the EEG IP using a Bayesian framework
      for ENET and ELASSO models. We propose a Structured Sparse Bayesian Learning
      algorithm based on combining the Empirical Bayes and the iterative coordinate
      descent procedures to estimate both the parameters and hyperparameters. Using
      realistic simulations and avoiding the inverse crime we illustrate that our
      methods are able to recover complicated source setups more accurately and with a
      more robust estimation of the hyperparameters and behavior under different
      sparsity scenarios than classical LORETA, ENET and LASSO Fusion solutions. We
      also solve the EEG IP using data from a visual attention experiment, finding more
      interpretable neurophysiological patterns with our methods. The Matlab codes used
      in this work, including Simulations, Methods, Quality Measures and Visualization
      Routines are freely available in a public website.

PMID- 29200988
TI  - Molecular signaling mechanisms behind polyphenol-induced bone anabolism.
AB  - For millennia, in the different cultures all over the world, plants have been
      extensively used as a source of therapeutic agents with wide-ranging medicinal
      applications, thus becoming part of a rational clinical and pharmacological
      investigation over the years. As bioactive molecules, plant-derived polyphenols
      have been demonstrated to exert many effects on human health by acting on
      different biological systems, thus their therapeutic potential would represent a
      novel approach on which natural product-based drug discovery and development
      could be based in the future. Many reports have provided evidence for the
      benefits derived from the dietary supplementation of polyphenols in the
      prevention and treatment of osteoporosis. Polyphenols are able to protect the
      bone, thanks to their antioxidant properties, as well as their anti-inflammatory
      actions by involving diverse signaling pathways, thus leading to bone anabolic
      effects and decreased bone resorption. This review is meant to summarize the
      research works performed so far, by elucidating the molecular mechanisms of
      action of polyphenols in a bone regeneration context, aiming at a better
      understanding of a possible application in the development of medical devices for
      bone tissue regeneration.

PMID- 29200993
TI  - Brain Sexual Differentiation and Requirement of SRY: Why or Why Not?
AB  - Brain sexual differentiation is orchestrated by precise coordination of sex
      steroid hormones. In some species, programming of select male brain regions is
      dependent upon aromatization of testosterone to estrogen. In mammals, these
      hormones surge during the organizational and activational periods that occur
      during perinatal development and adulthood, respectively. In various fish and
      reptiles, incubation temperature during a critical embryonic period results in
      male or female sexual differentiation, but this can be overridden in males by
      early exposure to estrogenic chemicals. Testes development in mammals requires a
      Y chromosome and testis determining gene SRY (in humans)/Sry (all other therian
      mammals), although there are notable exceptions. Two species of spiny rats: Amami
      spiny rat (Tokudaia osimensis) and Tokunoshima spiny rat (Tokudaia
      tokunoshimensis) and two species of mole voles (Ellobius lutescens and Ellobius
      tancrei), lack a Y chromosome/Sry and possess an XO chromosome system in both
      sexes. Such rodent species, prototherians (monotremes, who also lack Sry), and
      fish and reptile species that demonstrate temperature sex determination (TSD)
      seemingly call into question the requirement of Sry for brain sexual
      differentiation. This review will consider brain regions expressing SRY/Sry in
      humans and rodents, respectively, and potential roles of SRY/Sry in the brain
      will be discussed. The evidence from various taxa disputing the requirement of
      Sry for brain sexual differentiation in mammals (therians and prototherians) and
      certain fish and reptilian species will be examined. A comparative approach to
      address this question may elucidate other genes, pathways, and epigenetic
      modifications stimulating brain sexual differentiation in vertebrate species,
      including humans.

PMID- 29200996
TI  - Regulation of Brown Adipose Tissue Activity by Interoceptive CNS Pathways: The
      interaction between Brain and Periphery.
AB  - To maintain thermal homeostasis, specific thermogenic tissues are under the
      control of central thermoregulatory networks that regulate the body's response to
      thermal challenges. One of these mechanisms involves non-shivering thermogenesis
      in brown adipose tissue (BAT), which is activated in cold environments in order
      to defend the body against physical damage as a result of hypothermia. The
      objective of our study was to assess the interaction between CNS thermoregulatory
      pathways and sympathetic innervation in BAT during a cold exposure paradigm. Our
      results show that an innocuous whole-body cooling paradigm induces significant
      differences in fMRI BOLD signal at the location of the right anterior insula and
      the red nucleus/substantia nigra region, between lean subjects with high levels
      of sympathetic innervation in supraclavicular BAT (BAT+ group), and subjects with
      low levels of sympathetic innervation (BAT- group). Specifically, results
      indicate significantly larger fMRI BOLD signal changes between periods of cooling
      and warming of the skin in the BAT+ (as compared to BAT-) group at the location
      of the right anterior insula. In contrast, the BAT+ group showed significantly
      smaller fMRI BOLD signal changes in the midbrain between periods of skin cooling
      and warming. Our findings are consistent with a hierarchical thermoregulatory
      control system that involves the initiation of inhibitory signals from the right
      anterior insula toward midbrain areas that normally exert tonic inhibition on the
      medullary raphe, from where BAT is directly innervated. Our data suggests that
      exposure to cold elicits differential neuronal activity in interoceptive
      regulatory centers of subjects with high and low level of sympathetic
      innervation. As a result, the variability of cold-activated BAT mass observed in
      humans might be, in part, yoked to different sensitivities of interoceptive
      cortical brain areas to skin temperature changes.

PMID- 29200995
TI  - SSRI and Motor Recovery in Stroke: Reestablishment of Inhibitory Neural Network
      Tonus.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the
      field of the neuromodulation not only because of their anti-depressive effects
      but also due to their ability to promote plasticity and enhance motor recovery in
      patients with stroke. Recent studies showed that fluoxetine promotes motor
      recovery after stroke through its effects on the serotonergic system enhancing
      motor outputs and facilitating long term potentiation, key factors in motor
      neural plasticity. However, little is known in regards of the exact mechanisms
      underlying these effects and several aspects of it remain poorly understood. In
      this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in
      particular fluoxetine, modulate inhibitory pathways, and that this modulation
      enhances reorganization and reestablishment of excitatory-inhibitory control;
      these effects play a key role in learning induced plasticity in neural circuits
      involved in the promotion of motor recovery after stroke. This discussion aims to
      provide important insights and rationale for the development of novel strategies
      for stroke motor rehabilitation.

PMID- 29200997
TI  - Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory
      Neuron Activity?
AB  - In this review article, we summarize the current insight on the role of Connexin-
      and Pannexin-based channels as modulators of sensory neurons. The somas of
      sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose
      ganglia). It is well known that within sensory ganglia, sensory neurons do not
      form neither electrical nor chemical synapses. One of the reasons for this is
      that each soma is surrounded by glial cells, known as satellite glial cells
      (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably
      pannexons located at SGCs have an important role in paracrine communication
      between glial cells and sensory neurons. This communication may be exerted via
      the release of bioactive molecules from SGCs and their subsequent action on
      receptors located at the soma of sensory neurons. The glio-neuronal communication
      seems to be relevant for the establishment of chronic pain, hyperalgesia and
      pathologies associated with tissue inflammation. Based on the current literature,
      it is possible to propose that Cx43 hemichannels expressed in SGCs could be a
      novel pharmacological target for treating chronic pain, which need to be directly
      evaluated in future studies.

PMID- 29200998
TI  - Attenuation of the Infiltration of Angiotensin II Expressing CD3+ T-Cells and the
      Modulation of Nerve Growth Factor in Lumbar Dorsal Root Ganglia - A Possible
      Mechanism Underpinning Analgesia Produced by EMA300, An Angiotensin II Type 2
      (AT2) Receptor Antagonist.
AB  - Recent preclinical and proof-of-concept clinical studies have shown promising
      analgesic efficacy of selective small molecule angiotensin II type 2 (AT2)
      receptor antagonists in the alleviation of peripheral neuropathic pain. However,
      their cellular and molecular mechanism of action requires further investigation.
      To address this issue, groups of adult male Sprague-Dawley rats with fully
      developed unilateral hindpaw hypersensitivity, following chronic constriction
      injury (CCI) of the sciatic nerve, received a single intraperitoneal bolus dose
      of the small molecule AT2 receptor antagonist, EMA300 (10 mg kg-1), or vehicle.
      At the time of peak EMA300-mediated analgesia (~1 h post-dosing), groups of CCI
      rats administered either EMA300 or vehicle were euthanized. A separate group of
      rats that underwent sham surgery were also included. The lumbar (L4-L6) dorsal
      root ganglia (DRGs) were obtained from all experimental cohorts and processed for
      immunohistochemistry and western blot studies. In vehicle treated CCI-rats, there
      was a significant increase in the expression levels of angiotensin II (Ang II),
      but not the AT2 receptor, in the ipsilateral lumbar DRGs. The elevated levels of
      Ang II in the ipsilateral lumbar DRGs of CCI-rats were at least in part
      contributed by CD3+ T-cells, satellite glial cells (SGCs) and subsets of neurons.
      Our findings suggest that the analgesic effect of EMA300 in CCI-rats involves
      multimodal actions that appear to be mediated at least in part by a significant
      reduction in the otherwise increased expression levels of Ang II as well as the
      number of Ang II-expressing CD3+ T-cells in the ipsilateral lumbar DRGs of CCI
      rats. Additionally, the acute anti-allodynic effects of EMA300 in CCI-rats were
      accompanied by rescue of the otherwise decreased expression of mature nerve
      growth factor (NGF) in the ipsilateral lumbar DRGs of CCI-rats. In contrast, the
      increased expression levels of TrkA and glial fibrillary acidic protein in the
      ipsilateral lumbar DRGs of vehicle-treated CCI-rats were not attenuated by a
      single bolus dose of EMA300. Consistent with our previous findings, there was
      also a significant decrease in the augmented levels of the downstream mediators
      of Ang II/AT2 receptor signaling, i.e., phosphorylated-p38 mitogen-activated
      protein kinase (MAPK) and phosphorylated-p44/p42 MAPK, in the ipsilateral lumbar
      DRGs.

PMID- 29200999
TI  - Confirming a Role for alpha9nAChRs and SK Potassium Channels in Type II Hair
      Cells of the Turtle Posterior Crista.
AB  - In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs)
      synapse on type II hair cells, bouton afferents innervating type II hair cells,
      and afferent calyces innervating type I hair cells. Electrical stimulation of
      VENs releases acetylcholine (ACh) at these synapses to exert diverse effects on
      afferent background discharge including rapid inhibition of bouton afferents and
      excitation of calyx-bearing afferents. Efferent-mediated inhibition is most
      pronounced in bouton afferents innervating type II hair cells near the torus, but
      becomes progressively smaller and briefer when moving longitudinally through the
      crista toward afferents innervating the planum. Sharp-electrode recordings have
      inferred that efferent-mediated inhibition of bouton afferents requires the
      sequential activation of alpha9-containing nicotinic ACh receptors
      (alpha9*nAChRs) and small-conductance, calcium-dependent potassium channels (SK)
      in type II hair cells. Gradations in the strength of efferent-mediated inhibition
      across the crista likely reflect variations in alpha9*nAChRs and/or SK activation
      in type II hair cells from those different regions. However, in turtle cristae,
      neither inference has been confirmed with direct recordings from type II hair
      cells. To address these gaps, we performed whole-cell, patch-clamp recordings
      from type II hair cells within a split-epithelial preparation of the turtle
      posterior crista. Here, we can easily visualize and record hair cells while
      maintaining their native location within the neuroepithelium. Consistent with
      alpha9*nAChR/SK activation, ACh-sensitive currents in type II hair cells were
      inward at hyperpolarizing potentials but reversed near -90 mV to produce outward
      currents that typically peaked around -20 mV. ACh-sensitive currents were largest
      in torus hair cells but absent from hair cells near the planum. In current clamp
      recordings under zero-current conditions, ACh robustly hyperpolarized type II
      hair cells. ACh-sensitive responses were reversibly blocked by the alpha9nAChR
      antagonists ICS, strychnine, and methyllycaconitine as well as the SK antagonists
      apamin and UCL1684. Intact efferent terminals in the split-epithelial preparation
      spontaneously released ACh that also activated alpha9*nAChRs/SK in type II hair
      cells. These release events were accelerated with high-potassium external
      solution and all events were blocked by strychnine, ICS, methyllycaconitine, and
      apamin. These findings provide direct evidence that activation of alpha9*nAChR/SK
      in turtle type II hair cells underlies efferent-mediated inhibition of bouton
      afferents.

PMID- 29201001
TI  - Sociality Affects REM Sleep Episode Duration Under Controlled Laboratory
      Conditions in the Rock Hyrax, Procavia capensis.
AB  - The rock hyrax, Procavia capensis, is a highly social, diurnal mammal. In the
      current study several physiologically measurable parameters of sleep, as well as
      the accompanying behavior, were recorded continuously from five rock hyraxes, for
      72 h under solitary (experimental animal alone in the recording chamber), and
      social conditions (experimental animal with 1 or 2 additional, non-implanted
      animals in the recording chamber). The results revealed no significant
      differences between solitary and social conditions for total sleep times, number
      of episodes, episode duration or slow wave activity (SWA) for all states
      examined. The only significant difference observed between social and solitary
      conditions was the average duration of rapid eye movement (REM) sleep episodes.
      REM sleep episode duration was on average 20 s and 40 s longer under social
      conditions daily and during the dark period, respectively. It is hypothesized
      that the increase in REM sleep episode duration under social conditions could
      possibly be attributed to improved thermoregulation strategies, however
      considering the limited sample size and design of the current study further
      investigations are needed to confirm this finding. Whether the conclusions and
      the observations made in this study can be generalized to all naturally socially
      sleeping mammals remains an open question.

PMID- 29201000
TI  - Striatal Galphaolf/cAMP Signal-Dependent Mechanism to Generate Levodopa-Induced
      Dyskinesia in Parkinson's Disease.
AB  - The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA)
      deficiency due to a progressive degeneration of nigral dopaminergic cells.
      Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a
      long-term daily administration of levodopa often develops levodopa-induced
      dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine
      monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the
      principal neurons of the striatum, which are roughly halved with striatonigral
      MSNs by striatopallidal MSNs. The olfactory type G-protein alpha subunit
      (Galphaolf) represents an important regulator of the cAMP signal activities in
      the striatum, where it positively couples with D1-type dopamine receptor (D1R)
      and adenosine A2A receptor (A2AR) to increase cAMP production in the MSNs.
      Notably, D1Rs are primarily expressed in striatonigral MSNs, whereas D2Rs and
      A2ARs are expressed in striatopallidal MSNs. Based on the evidence obtained from
      parkinsonian mice, we hypothesized that in the DA-denervated striatum with D1R
      hypersensitivity, a repeated and pulsatile exposure to levodopa might cause a
      usage-induced degradation of Galphaolf proteins in striatal MSNs, resulting in
      increased and decreased levels of Galphaolf protein in the striatonigral and
      striatopallidal MSNs, respectively. As a principal cause for generating LID, this
      might lead to an increased responsiveness to levodopa exposure in both
      striatonigral and striatopallidal MSNs. Our hypothesis reinforces the long
      standing concept that LID might result from the reduced activity of the
      striatopallidal pathway and has important clinical implications.

PMID- 29201003
TI  - Electrical Activity in a Time-Delay Four-Variable Neuron Model under
      Electromagnetic Induction.
AB  - To investigate the effect of electromagnetic induction on the electrical activity
      of neuron, the variable for magnetic flow is used to improve Hindmarsh-Rose
      neuron model. Simultaneously, due to the existence of time-delay when signals are
      propagated between neurons or even in one neuron, it is important to study the
      role of time-delay in regulating the electrical activity of the neuron. For this
      end, a four-variable neuron model is proposed to investigate the effects of
      electromagnetic induction and time-delay. Simulation results suggest that the
      proposed neuron model can show multiple modes of electrical activity, which is
      dependent on the time-delay and external forcing current. It means that suitable
      discharge mode can be obtained by selecting the time-delay or external forcing
      current, which could be helpful for further investigation of electromagnetic
      radiation on biological neuronal system.

PMID- 29201002
TI  - A Comparison of Different Slicing Planes in Preservation of Major Hippocampal
      Pathway Fibers in the Mouse.
AB  - The hippocampus plays a critical role in learning and memory and higher cognitive
      functions, and its dysfunction has been implicated in various neuropathological
      disorders. Electrophysiological recording undertaken in live brain slices is one
      of the most powerful tools for investigating hippocampal cellular and network
      activities. The plane for cutting the slices determines which afferent and/or
      efferent connections are best preserved, and there are three commonly used
      slices: hippocampal-entorhinal cortex (HEC), coronal and transverse. All three
      slices have been widely used for studying the major afferent hippocampal pathways
      including the perforant path (PP), the mossy fibers (MFs) and the Schaffer
      collaterals (SCs). Surprisingly, there has never been a systematic investigation
      of the anatomical and functional consequences of slicing at a particular angle.
      In the present study, we focused on how well fiber pathways are preserved from
      the entorhinal cortex (EC) to the hippocampus, and within the hippocampus, in
      slices generated by sectioning at different angles. The postmortem neural tract
      tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI)
      was used to label afferent fibers to hippocampal principal neurons in fixed
      slices or whole brains. Laser scanning confocal microscopy was adopted for
      imaging DiI-labeled axons and terminals. We demonstrated that PP fibers were well
      preserved in HEC slices, MFs in both HEC and transverse slices and SCs in all
      three types of slices. Correspondingly, field excitatory postsynaptic potentials
      (fEPSPs) could be consistently evoked in HEC slices when stimulating PP fibers
      and recorded in stratum lacunosum-moleculare (sl-m) of area CA1, and when
      stimulating the dentate granule cell layer (gcl) and recording in stratum lucidum
      (sl) of area CA3. The MF evoked fEPSPs could not be recorded in CA3 from coronal
      slices. In contrast to our DiI-tracing data demonstrating severely truncated PP
      fibers in coronal slices, fEPSPs could still be recorded in CA1 sl-m in this
      plane, suggesting that an additional afferent fiber pathway other than PP might
      be involved. The present study increases our understanding of which hippocampal
      pathways are best preserved in the three most common brain slice preparations,
      and will help investigators determine the appropriate slices to use for
      physiological studies depending on the subregion of interest.

PMID- 29201004
TI  - Subjective Cognitive Decline as a Preclinical Marker for Alzheimer's Disease: The
      Challenge of Stability Over Time.

PMID- 29201005
TI  - High Concentrations of Rosiglitazone Reduce mRNA and Protein Levels of LRP1 in
      HepG2 Cells.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic
      receptor involved in the uptake of a variety of molecules, such as apoE, alpha2
      macroglobulin, and the amyloid beta peptide (Abeta), for either transcellular
      transport, protein trafficking or lysosomal degradation. The LRP1 gene can be
      transcribed upon activation of peroxisome proliferator receptor activated-gamma
      (PPARgamma) by the potent PPARgamma agonist, rosiglitazone (RGZ). In previous
      studies, RGZ was shown to upregulate LRP1 levels in concentrations between 0.1
      and 5 MUM in HepG2 cells. In this study, we sought to replicate previous studies
      and to investigate the molecular mechanism by which high concentrations of RGZ
      reduce LRP1 levels in HepG2 cells. Our data confirmed that transcriptional
      activation of LRP1 occurred in response to RGZ at 3 and 10 MUM, in agreement with
      the study reported by Moon et al. (2012a). On the other hand, we found that high
      concentrations of RGZ decreased both mRNA and protein levels of LRP1.
      Mechanistically, transcriptional dysregulation of LRP1 was affected by the
      downregulation of PPARgamma in a time- and concentration-dependent manner.
      However, downregulation of PPARgamma was responsible for only 40% of the LRP1
      reduction and thereby the remaining loss of LRP1 (60%) was found to be through
      degradation in the lysosomal system. In conclusion, our findings demonstrate the
      mechanisms by which high concentrations of RGZ caused LRP1 levels to be reduced
      in HepG2 cells. Taken together, this data will be helpful to better explain the
      pharmacological modulation of this pivotal membrane receptor by PPARgamma
      agonists.

PMID- 29201006
TI  - Blockade of Eosinophil-Induced Bronchial Epithelial-Mesenchymal Transition with a
      Geranyl Acetophenone in a Coculture Model.
AB  - Epithelial-mesenchymal transition (EMT) is currently recognized as the main
      cellular event that contributes to airway remodeling. Eosinophils can induce EMT
      in airway epithelial cells via increased transforming growth factor (TGF)-beta
      production. We assessed the effect of synthetic 2,4,6-trihydroxy-3-geranyl
      acetophenone (tHGA) upon eosinophil-induced EMT in a cellular model. The human
      eosinophil cell line EoL-1 was used to induce EMT in BEAS-2B human bronchial
      epithelial cells. The induction of EMT was dose-dependently suppressed following
      tHGA treatment in which the epithelial morphology and E-cadherin expression were
      not altered. Protein and mRNA expression of vimentin, collagen I and fibronectin
      in eosinophil-induced epithelial cells were also significantly suppressed by tHGA
      treatment. Following pathway analysis, we showed that tHGA suppressed eosinophil
      induced activator protein-1-mediated TGF-beta production by targeting c-Jun N
      terminal kinase and phosphoinositide 3-kinase signaling pathways. These findings
      corroborated previous findings on the ability of tHGA to inhibit experimental
      murine airway remodeling.

PMID- 29201007
TI  - Erythropoietin Attenuates Postoperative Cognitive Dysfunction by Shifting
      Macrophage Activation toward the M2 Phenotype.
AB  - Postoperative cognitive dysfunction (POCD) may be driven by transference of the
      innate immune response to the brain after aseptic surgical damage. Macrophages
      are key mediators of innate immunity that can display a pro-inflammatory M1
      phenotype or an anti-inflammatory M2 phenotype. Erythropoietin (EPO) is a
      hematopoietic hormone that exerts anti-inflammatory effects by influencing
      macrophage function. We hypothesized that EPO would prevent POCD by promoting
      macrophage phenotype switching to the M2 phenotype post-surgery. To evaluate the
      effects of EPO on POCD and macrophage polarization post-surgery, we administered
      EPO (5,000 U/kg) with or without an arginase inhibitor (amino-6-boronohexanoic
      acid, 10 mg/kg) to ICR mice before and after abdominal surgery. Forty-eight hours
      post-surgery, we assessed memory, synapse function, and macrophage/microglial
      phenotypes in the spleen and hippocampus. We also investigated M1/M2 phenotypes
      in RAW264.7 and BV2 cells stimulated with lipopolysaccharide and interferon-gamma
      (M1 inducers) in the presence or absence of EPO. EPO prevented POCD, decreased
      surgery-related synaptic dysfunction, and attenuated pro-inflammatory cytokine
      generation in the hippocampus. Moreover, EPO suppressed M1-related genes
      expression and promoted M2 genes expression in the spleen and hippocampus post
      surgery. Furthermore, EPO decreased the proportions of macrophages/microglia
      expressing an M1 surface marker (CD40) and increased those expressing an M2
      surface marker (CD206). Arginase inhibition abolished the beneficial effects of
      EPO on POCD. In vitro, EPO treatment promoted switching of RAW264.7 and BV2 cells
      stimulated with M1 inducers to an M2 phenotype. In conclusion, EPO prevents POCD
      by promoting macrophage phenotype switching toward the M2 phenotype.

PMID- 29201008
TI  - Dose-Dependent Rescue of KO Amelogenin Enamel by Transgenes in Vivo.
AB  - Mice lacking amelogenin (KO) have hypoplastic enamel. Overexpression of the most
      abundant amelogenin splice variant M180 and LRAP transgenes can substantially
      improve KO enamel, but only ~40% of the incisor thickness is recovered and the
      prisms are not as tightly woven as in WT enamel. This implies that the
      compositional complexity of the enamel matrix is required for different aspects
      of enamel formation, such as organizational structure and thickness. The question
      arises, therefore, how important the ratio of different matrix components, and in
      particular amelogenin splice products, is in enamel formation. Can optimal
      expression levels of amelogenin transgenes representing both the most abundant
      splice variants and cleavage product at protein levels similar to that of WT
      improve the enamel phenotype of KO mice? Addressing this question, our objective
      was here to understand dosage effects of amelogenin transgenes (Tg) representing
      the major splice variants M180 and LRAP and cleavage product CTRNC on enamel
      properties. Amelogenin KO mice were mated with M180Tg, CTRNCTg and LRAPTg mice to
      generate M180Tg and CTRNCTg double transgene and M180Tg, CTRNCTg, LRAPTg triple
      transgene mice with transgene hemizygosity (on one allelle) or homozygosity (on
      both alleles). Transgene homo- vs. hemizygosity was determined by qPCR and
      relative transgene expression confirmed by Western blot. Enamel volume and
      mineral density were analyzed by microCT, thickness and structure by SEM, and
      mechanical properties by Vickers microhardness testing. There were no differences
      in incisor enamel thickness between amelogenin KO mice with three or two
      different transgenes, but mice homozygous for a given transgene had significantly
      thinner enamel than mice hemizygous for the transgene (p < 0.05). The presence of
      the LRAPTg did not improve the phenotype of M180Tg/CTRNCTg/KO enamel. In the
      absence of endogenous amelogenin, the addition of amelogenin transgenes
      representing the most abundant splice variants and cleavage product can rescue
      abnormal enamel properties and structure, but only up to a maximum of ~80% that
      of molar and ~40% that of incisor wild-type enamel.

PMID- 29201009
TI  - In Vitro and In Silico Risk Assessment in Acquired Long QT Syndrome: The Devil Is
      in the Details.
AB  - Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1
      potassium channel in the heart, is characterized by delayed cardiac myocyte
      repolarization, prolongation of the T interval on the ECG, syncope and sudden
      cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes
      (TdP). In recent years, efforts are underway through the Comprehensive in vitro
      proarrhythmic assay (CiPA) initiative, to develop better tests for this drug
      induced arrhythmia based in part on in silico simulations of pharmacological
      disruption of repolarization. However, drug binding to Kv11.1 is more complex
      than a simple binary molecular reaction, meaning simple steady state measures of
      potency are poor surrogates for risk. As a result, there is a plethora of
      mechanistic detail describing the drug/Kv11.1 interaction-such as drug binding
      kinetics, state preference, temperature dependence and trapping-that needs to be
      considered when developing in silico models for risk prediction. In addition to
      this, other factors, such as multichannel pharmacological profile and the nature
      of the ventricular cell models used in simulations also need to be considered in
      the search for the optimum in silico approach. Here we consider how much of
      mechanistic detail needs to be included for in silico models to accurately
      predict risk and further, how much of this detail can be retrieved from protocols
      that are practical to implement in high throughout screens as part of next
      generation of preclinical in silico drug screening approaches?

PMID- 29201011
TI  - Development and Validation of Two Instruments Measuring Intrinsic, Extraneous,
      and Germane Cognitive Load.
AB  - Cognitive Load Theory is one of the most powerful research frameworks in
      educational research. Beside theoretical discussions about the conceptual parts
      of cognitive load, the main challenge within this framework is that there is
      still no measurement instrument for the different aspects of cognitive load,
      namely intrinsic, extraneous, and germane cognitive load. Hence, the goal of this
      paper is to develop a differentiated measurement of cognitive load. In Study 1 (N
      = 97), we developed and analyzed two strategies to measure cognitive load in a
      differentiated way: (1) Informed rating: We trained learners in differentiating
      the concepts of cognitive load, so that they could rate them in an informed way.
      They were asked then to rate 24 different learning situations or learning
      materials related to either high or low intrinsic, extraneous, or germane load.
      (2) Naive rating: For this type of rating of cognitive load we developed a
      questionnaire with two to three items for each type of load. With this
      questionnaire, the same learning situations had to be rated. In the second study
      (N = between 65 and 95 for each task), we improved the instrument for the naive
      rating. For each study, we analyzed whether the instruments are reliable and
      valid, for Study 1, we also checked for comparability of the two measurement
      strategies. In Study 2, we conducted a simultaneous scenario based factor
      analysis. The informed rating seems to be a promising strategy to assess the
      different aspects of cognitive load, but it seems not economic and feasible for
      larger studies and a standardized training would be necessary. The improved
      version of the naive rating turned out to be a useful, feasible, and reliable
      instrument. Ongoing studies analyze the conceptual validity of this measurement
      with up to now promising results.

PMID- 29201010
TI  - Microglia and Brain Plasticity in Acute Psychosis and Schizophrenia Illness
      Course: A Meta-Review.
AB  - Objective: Schizophrenia poses a tremendous health, social, and economic burden
      upon patients and society, indicating current treatment options remain
      inadequate. Recent findings from several lines of evidence have pointed to the
      importance of immune system involvement in not only premorbid neurodevelopmental
      but also subsequent symptom generation and aging processes of brain change in
      schizophrenia. In this meta-review, we use the summarized evidence from recent
      quantitative systematic reviews (SRs) and meta-analyses of several subspecialties
      to critically evaluate the hypothesis that immune-related processes shape the
      symptomatic presentation and illness course of schizophrenia, both directly and
      indirectly through altered neuroplasticity. Methods: We performed a data search
      in PubMed for English language SRs and meta-analyses from 2010 to 2017. The
      methodological quality of the SRs was assessed with the AMSTAR instrument. In
      addition, we review in this paper 11 original publications on translocator
      protein (TSPO) positron emission tomography (PET) imaging in schizophrenia.
      Results: We reviewed 26 SRs and meta-analyses. Evidence from clinical
      observational studies of inflammatory or immunological markers and randomized
      controlled drug trials of immunomodulatory compounds as add-on in the treatment
      of schizophrenia suggests psychotic exacerbations are accompanied by
      immunological changes different from those seen in non-acute states, and that the
      symptoms of schizophrenia can be modified by compounds such as non-steroidal anti
      inflammatory drug and minocycline. Information derived from post-mortem brain
      tissue analysis and PET neuroimaging studies to evaluate microglial activation
      have added new perspectives to the available evidence, yet these results are very
      heterogeneous. Each research domain comes with unique opportunities as well as
      inherent limitations. A better understanding of the (patho-)physiology of
      microglial cells and their role in neuroplasticity is key to interpreting the
      immune-related findings in the context of schizophrenia illness exacerbations and
      progression. Conclusion: Evidence from clinical studies analyzing patients' blood
      and cerebrospinal fluid samples, neuroimaging and post-mortem brain tissue
      suggests that aberrant immune responses may define schizophrenia illness' course
      through altered neuroplasticity representing abnormal aging processes. Most
      findings are however prone to bias and confounding, and often non-specific to
      schizophrenia, and a multidisciplinary translational approach is needed to
      consolidate these findings and link them to other schizophrenia hypotheses.

PMID- 29201012
TI  - Telling Friend from Foe: Listeners Are Unable to Identify In-Group and Out-Group
      Members from Heard Laughter.
AB  - Group membership is important for how we perceive others, but although perceivers
      can accurately infer group membership from facial expressions and spoken
      language, it is not clear whether listeners can identify in- and out-group
      members from non-verbal vocalizations. In the current study, we examined
      perceivers' ability to identify group membership from non-verbal vocalizations of
      laughter, testing the following predictions: (1) listeners can distinguish
      between laughter from different nationalities and (2) between laughter from their
      in-group, a close out-group, and a distant out-group, and (3) greater exposure to
      laughter from members of other cultural groups is associated with better
      performance. Listeners (n = 814) took part in an online forced-choice
      classification task in which they were asked to judge the origin of 24 laughter
      segments. The responses were analyzed using frequentist and Bayesian statistical
      analyses. Both kinds of analyses showed that listeners were unable to accurately
      identify group identity from laughter. Furthermore, exposure did not affect
      performance. These results provide a strong and clear demonstration that group
      identity cannot be inferred from laughter.

PMID- 29201013
TI  - Aiming at a Moving Target: Theoretical and Methodological Considerations in the
      Study of Intraindividual Goal Conflict between Personal Goals.
AB  - Multiple-goal pursuit and conflict between personal life-defining goals can be
      considered part of everyday business in most individuals' lives. Given the
      potentially detrimental effects of goal conflict-for example, impaired well-being
      or poor performance-the literature on goal conflict is surprisingly scattered due
      to heterogeneous methodological approaches and technical terms. Little empirical
      research has addressed the conceptualization of goal conflict against the
      background of differing understandings from a structure-like and a process-like
      perspective. In the present article, we outline theoretical foundations of goal
      conflict from two perspectives: a structure- and a process-like perspective.
      Based on a comparative analysis and integration of these two perspectives, we
      systematically review empirical studies on goal conflict over 30 years of
      research. In doing so, we identify and discuss important conceptual dimensions of
      goal conflict, namely, goal conflict as a cognitive construct and an experiential
      instance, a focus on goal interrelations or on specific goal properties, and
      resource vs. inherent conflict, and the potential of these distinctions to
      further research on goal conflict. Finally, we present major challenges and pose
      questions that need to be addressed by future research.

PMID- 29201014
TI  - Impaired Interoceptive Accuracy in Semantic Variant Primary Progressive Aphasia.
AB  - Background: Interoception (the perception of internal bodily sensations) is
      strongly linked to emotional experience and sensitivity to the emotions of others
      in healthy subjects. Interoceptive impairment may contribute to the profound
      socioemotional symptoms that characterize frontotemporal dementia (FTD)
      syndromes, but remains poorly defined. Methods: Patients representing all major
      FTD syndromes and healthy age-matched controls performed a heartbeat counting
      task as a measure of interoceptive accuracy. In addition, patients had volumetric
      MRI for voxel-based morphometric analysis, and their caregivers completed a
      questionnaire assessing patients' daily-life sensitivity to the emotions of
      others. Results: Interoceptive accuracy was impaired in patients with semantic
      variant primary progressive aphasia relative to healthy age-matched individuals,
      but not in behavioral variant frontotemporal dementia and nonfluent variant
      primary progressive aphasia. Impaired interoceptive accuracy correlated with
      reduced daily-life emotional sensitivity across the patient cohort, and with
      atrophy of right insula, cingulate, and amygdala on voxel-based morphometry in
      the impaired semantic variant group, delineating a network previously shown to
      support interoceptive processing in the healthy brain. Conclusion: Interoception
      is a promising novel paradigm for defining mechanisms of reduced emotional
      reactivity, empathy, and self-awareness in neurodegenerative syndromes and may
      yield objective measures for these complex symptoms.

PMID- 29201015
TI  - Role of Perinatal Inflammation in Neonatal Arterial Ischemic Stroke.
AB  - Based on the review of the literature, perinatal inflammation often induced by
      infection is the only consistent independent risk factor of neonatal arterial
      ischemic stroke (NAIS). Preclinical studies show that acute inflammatory
      processes take place in placenta, cerebral arterial wall of NAIS-susceptible
      arteries and neonatal brain. A top research priority in NAIS is to further
      characterize the nature and spatiotemporal features of the inflammatory processes
      involved in multiple levels of the pathophysiology of NAIS, to adequately design
      randomized control trials using targeted anti-inflammatory vasculo- and
      neuroprotective agents.

PMID- 29201016
TI  - The Promise of Systems Biology Approaches for Revealing Host Pathogen
      Interactions in Malaria.
AB  - Despite global eradication efforts over the past century, malaria remains a
      devastating public health burden, causing almost half a million deaths annually
      (WHO, 2016). A detailed understanding of the mechanisms that control malaria
      infection has been hindered by technical challenges of studying a complex
      parasite life cycle in multiple hosts. While many interventions targeting the
      parasite have been implemented, the complex biology of Plasmodium poses a major
      challenge, and must be addressed to enable eradication. New approaches for
      elucidating key host-parasite interactions, and predicting how the parasite will
      respond in a variety of biological settings, could dramatically enhance the
      efficacy and longevity of intervention strategies. The field of systems biology
      has developed methodologies and principles that are well poised to meet these
      challenges. In this review, we focus our attention on the Liver Stage of the
      Plasmodium lifecycle and issue a "call to arms" for using systems biology
      approaches to forge a new era in malaria research. These approaches will reveal
      insights into the complex interplay between host and pathogen, and could
      ultimately lead to novel intervention strategies that contribute to malaria
      eradication.

PMID- 29201017
TI  - Characterization of Metagenomes in Urban Aquatic Compartments Reveals High
      Prevalence of Clinically Relevant Antibiotic Resistance Genes in Wastewaters.
AB  - The dissemination of antimicrobial resistance (AMR) is an escalating problem and
      a threat to public health. Comparative metagenomics was used to investigate the
      occurrence of antibiotic resistant genes (ARGs) in wastewater and urban surface
      water environments in Singapore. Hospital and municipal wastewater (n = 6) were
      found to have higher diversity and average abundance of ARGs (303 ARG subtypes,
      197,816 x/Gb) compared to treated wastewater effluent (n = 2, 58 ARG subtypes,
      2,692 x/Gb) and surface water (n = 5, 35 subtypes, 7,985 x/Gb). A cluster
      analysis showed that the taxonomic composition of wastewaters was highly similar
      and had a bacterial community composition enriched in gut bacteria (Bacteroides,
      Faecalibacterium, Bifidobacterium, Blautia, Roseburia, Ruminococcus), the
      Enterobacteriaceae group (Klebsiella, Aeromonas, Enterobacter) and opportunistic
      pathogens (Prevotella, Comamonas, Neisseria). Wastewater, treated effluents and
      surface waters had a shared resistome of 21 ARGs encoding multidrug resistant
      efflux pumps or resistance to aminoglycoside, macrolide-lincosamide
      streptogramins (MLS), quinolones, sulfonamide, and tetracycline resistance which
      suggests that these genes are wide spread across different environments.
      Wastewater had a distinctively higher average abundance of clinically relevant,
      class A beta-lactamase resistant genes (i.e., blaKPC, blaCTX-M, blaSHV, blaTEM).
      The wastewaters from clinical isolation wards, in particular, had a exceedingly
      high levels of blaKPC-2 genes (142,200 x/Gb), encoding for carbapenem resistance.
      Assembled scaffolds (16 and 30 kbp) from isolation ward wastewater samples
      indicated this gene was located on a Tn3-based transposon (Tn4401), a
      mobilization element found in Klebsiella pneumonia plasmids. In the longer
      scaffold, transposable elements were flanked by a toxin-antitoxin (TA) system and
      other metal resistant genes that likely increase the persistence, fitness and
      propagation of the plasmid in the bacterial host under conditions of stress. A
      few bacterial species (Enterobacter cloacae, Klebsiella pneumoniae, Citrobacter
      freundii, Pseudomonas aeruginosa) that were cultured from the isolation ward
      wastewaters on CHROMagar media harbored the blaKPC-2 gene. This suggests that
      hospital wastewaters derived from clinical specialty wards are hotspots for the
      spread of AMR. Assembled scaffolds of other mobile genetic elements such as IncQ
      and IncF plasmids bearing quinolone resistance genes (qnrS1, qnrS2) and the class
      A beta-lactamase gene (blaTEM-1) were recovered in wastewater samples which may
      aid the transfer of AMR.

PMID- 29201018
TI  - Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained
      from Prostatic Tissue.
AB  - Inflammation is one of the hallmarks of prostate cancer. The origin of
      inflammation is unknown, but microbial infections are suspected to play a role.
      In previous studies, the Gram-positive, low virulent bacterium Cutibacterium
      (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue.
      It is unclear if the presence of the bacterium represents a true infection or a
      contamination. Here we investigated Cutibacterium acnes type II, also called
      subspecies defendens, which is the most prevalent type among prostatic C. acnes
      isolates. Genome sequencing of type II isolates identified large plasmids in
      several genomes. The plasmids are highly similar to previously identified linear
      plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based
      analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from
      cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative
      transfer. In addition, it contains a gene locus for tight adherence (tad) that is
      predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In
      subsequent experiments a tad locus-encoded putative pilin subunit was identified
      in the surface-exposed protein fraction of plasmid-positive C. acnes type II
      strains by mass spectrometry, indicating that the tad locus is functional.
      Additional plasmid-encoded proteins were detected in the secreted protein
      fraction, including two signal peptide-harboring proteins; the corresponding
      genes are specific for type II C. acnes, thus lacking from plasmid-positive type
      I C. acnes strains. Further support for the presence of Flp pili in C. acnes type
      II was provided by electron microscopy, revealing cell appendages in tad locus
      positive strains. Our study provides new insight in the most prevalent prostatic
      subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili
      in plasmid-positive strains. Such pili may support colonization and persistent
      infection of human prostates by C. acnes.

PMID- 29201019
TI  - Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30
      Capsulated E. coli in Mice.
AB  - Capsule depolymerase enzymes offer a promising class of new antibiotics. In vivo
      studies are encouraging but it is unclear how well this type of phage product
      will generalize in therapeutics, or whether different depolymerases against the
      same capsule function similarly. Here, in vivo efficacy was tested using cloned
      bacteriophage depolymerases against Escherichia coli strains with three different
      capsule types: K1, K5, and K30. When treating infections with the cognate capsule
      type in a mouse thigh model, the previously studied K1E depolymerase rescued
      poorly, whereas K1F, K1H, K5, and K30 depolymerases rescued well. K30 gp41 was
      identified as the catalytically active protein. In contrast to the in vivo
      studies, K1E enzyme actively degraded K1 capsule polysaccharide in vitro and
      sensitized K1 bacteria to serum killing. The only in vitro correlate of poor K1E
      performance in vivo was that the purified enzyme did not form the expected
      trimer. K1E appeared as an 18-mer which might limit its in vivo distribution.
      Overall, depolymerases were easily identified, cloned from phage genomes, and as
      purified proteins they proved generally effective.

PMID- 29201020
TI  - Recent Advances in the Recombinant Biosynthesis of Polyphenols.
AB  - Plants are the source of various natural compounds with pharmaceutical and
      nutraceutical importance which have shown numerous health benefits with
      relatively fewer side effects. However, extraction of these compounds from native
      producers cannot meet the ever-increasing demands of the growing population due
      to, among other things, the limited production of the active compound(s). Their
      production depends upon the metabolic demands of the plant and is also subjected
      to environmental conditions, abundance of crop species and seasonal variations.
      Moreover, their extraction from plants requires complex downstream processing and
      can also lead to the extinction of many useful plant varieties. Microbial
      engineering is one of the alternative approaches which can meet the global demand
      for natural products in an eco-friendly manner. Metabolic engineering of microbes
      or pathway reconstruction using synthetic biology tools and novel enzymes lead to
      the generation of a diversity of compounds (like flavonoids, stilbenes,
      anthocyanins etc.) and their natural and non-natural derivatives. Strain and
      pathway optimization, pathway regulation and tolerance engineering have produced
      microbial cell factories into which the metabolic pathway of plants can be
      introduced for the production of compounds of interest on an industrial scale in
      an economical and eco-friendly way. While microbial production of phytochemicals
      needs to further increase product titer if it is ever to become a commercial
      success. The present review covers the advancements made for the improvement of
      microbial cell factories in order to increase the product titer of recombinant
      polyphenolic compounds.

PMID- 29201021
TI  - PifC and Osa, Plasmid Weapons against Rival Conjugative Coupling Proteins.
AB  - Bacteria display a variety of mechanisms to control plasmid conjugation. Among
      them, fertility inhibition (FI) systems prevent conjugation of co-resident
      plasmids within donor cells. Analysis of the mechanisms of inhibition between
      conjugative plasmids could provide new alternatives to fight antibiotic
      resistance dissemination. In this work, inhibition of conjugation of broad host
      range IncW plasmids was analyzed in the presence of a set of co-resident
      plasmids. Strong FI systems against plasmid R388 conjugation were found in
      IncF/MOBF12 as well as in IncI/MOBP12 plasmids, represented by plasmids F and
      R64, respectively. In both cases, the responsible gene was pifC, known also to be
      involved in FI of IncP plasmids and Agrobacterium T-DNA transfer to plant cells.
      It was also discovered that the R388 gene osa, which affects T-DNA transfer, also
      prevented conjugation of IncP-1/MOBP11 plasmids represented by plasmids RP4 and
      R751. Conjugation experiments of different mobilizable plasmids, helped by either
      FI-susceptible or FI-resistant transfer systems, demonstrated that the
      conjugative component affected by both PifC and Osa was the type IV conjugative
      coupling protein. In addition, in silico analysis of FI proteins suggests that
      they represent recent acquisitions of conjugative plasmids, i.e., are not shared
      by members of the same plasmid species. This implies that FI are rapidly-moving
      accessory genes, possibly acting on evolutionary fights between plasmids for the
      colonization of specific hosts.

PMID- 29201022
TI  - Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to
      be a major global health problem. The inflammatory response during VL is
      characterized by the release of several cytokines and other pro-inflammatory
      mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of
      evolutionarily conserved membrane-bound surface receptors expressed on
      neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling
      events that drive cytokine production, degranulation, and phagocytosis. In
      certain inflammatory-associated diseases, TREM-1 can also be found as a soluble
      form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these
      studies, we now find that high levels of circulating sTREM-1 correlate directly
      with VL disease severity. In particular, high levels of sTREM-1 were observed in
      non-survivor VL patients. Furthermore, these levels of sTREM-1 positively
      correlated with liver size and negatively correlated with leukocyte counts and
      hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro
      to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while
      also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1
      levels are associated with increasing parasite ratio. Taken together, these
      studies suggest that L. infantum may modulate TREM-1 in neutrophils and high
      levels of this molecule is associated with severe VL.

PMID- 29201023
TI  - A Marine Actinomycete Rescues Caenorhabditis elegans from Pseudomonas aeruginosa
      Infection through Restitution of Lysozyme 7.
AB  - The resistance of Pseudomonas aeruginosa to conventional antimicrobial treatment
      is a major scourge in healthcare. Therefore, it is crucial that novel potent anti
      infectives are discovered. The aim of the present study is to screen marine
      actinomycetes for chemical entities capable of overcoming P. aeruginosa infection
      through mechanisms involving anti-virulence or host immunity activities. A total
      of 18 actinomycetes isolates were sampled from marine sediment of Songsong
      Island, Kedah, Malaysia. Upon confirming that the methanolic crude extract of
      these isolates do not display direct bactericidal activities, they were tested
      for capacity to rescue Caenorhabditis elegans infected with P. aeruginosa strain
      PA14. A hexane partition of the extract from one isolate, designated as
      Streptomyces sp. CCB-PSK207, could promote the survival of PA14 infected worms by
      more than 60%. Partial 16S sequence analysis on this isolate showed identity of
      99.79% with Streptomyces sundarbansensis. This partition did not impair feeding
      behavior of C. elegans worms. Tested on PA14, the partition also did not affect
      bacterial growth or its ability to colonize host gut. The production of biofilm,
      protease, and pyocyanin in PA14 were uninterrupted, although there was an
      increase in elastase production. In lys-7::GFP worms, this partition was shown to
      induce the expression of lysozyme 7, an important innate immunity defense
      molecule that was repressed during PA14 infection. GC-MS analysis of the
      bioactive fraction of Streptomyces sp. CCB-PSK207 revealed the presence of methyl
      esters of branched saturated fatty acids. In conclusion, this is the first report
      of a marine actinomycete producing metabolites capable of rescuing C. elegans
      from PA14 through a lys-7 mediated activity.

PMID- 29201024
TI  - Involvement of the Transcriptional Coactivator ThMBF1 in the Biocontrol Activity
      of Trichoderma harzianum.
AB  - Trichoderma harzianum is a filamentous fungus well adapted to different
      ecological niches. Owing to its ability to antagonize a wide range of plant
      pathogens, it is used as a biological control agent in agriculture. Selected
      strains of T. harzianum are also able to increase the tolerance of plants to
      biotic and abiotic stresses. However, little is known about the regulatory
      elements of the T. harzianum transcriptional machinery and their role in the
      biocontrol by this species. We had previously reported the involvement of the
      transcription factor THCTF1 in the T. harzianum production of the secondary
      metabolite 6-pentyl-pyrone, an important volatile compound related to
      interspecies cross-talk. Here, we performed a subtractive hybridization to
      explore the genes regulated by THCTF1, allowing us to identify a multiprotein
      bridging factor 1 (mbf1) homolog. The gene from T. harzianum T34 was isolated and
      characterized, and the generated Thmbf1 overexpressing transformants were used to
      investigate the role of this gene in the biocontrol abilities of the fungus
      against two plant pathogens. The transformants showed a reduced antifungal
      activity against Fusarium oxysporum f. sp. lycopersici race 2 (FO) and Botrytis
      cinerea (BC) in confrontation assays on discontinuous medium, indicating that the
      Thmbf1 gene could affect T. harzianum production of volatile organic compounds
      (VOC) with antifungal activity. Moreover, cellophane and dialysis membrane assays
      indicated that Thmbf1 overexpression affected the production of low molecular
      weight secreted compounds with antifungal activity against FO. Intriguingly, no
      correlation in the expression profiles, either in rich or minimal medium, was
      observed between Thmbf1 and the master regulator gene cross-pathway control
      (cpc1). Greenhouse assays allowed us to evaluate the biocontrol potential of T.
      harzianum strains against BC and FO on susceptible tomato plants. The wild type
      strain T34 significantly reduced the necrotic leaf lesions caused by BC while
      plants treated with the Thmbf1-overexpressing transformants exhibited an
      increased susceptibility to this pathogen. The percentages of Fusarium wilt
      disease incidence and values of aboveground dry weight showed that T34 did not
      have biocontrol activity against FO, at least in the 'Moneymaker' tomato variety,
      and that Thmbf1 overexpression increased the incidence of this disease. Our
      results show that the Thmbf1 overexpression in T34 negatively affects its
      biocontrol mechanisms.

PMID- 29201025
TI  - Regulation of Neuroinflammation: What Role for the Tumor Necrosis Factor-Like
      Weak Inducer of Apoptosis/Fn14 Pathway?
AB  - Observed in many central nervous system diseases, neuroinflammation (NI) proceeds
      from peripheral immune cell infiltration into the parenchyma, from cytokine
      secretion and from oxidative stress. Astrocytes and microglia also get activated
      and proliferate. NI manifestations and consequences depend on its context and on
      the acute or chronic aspect of the disease. The tumor necrosis factor-like weak
      inducer of apoptosis (TWEAK)/Fn14 pathway has been involved in chronic human
      inflammatory pathologies such as neurodegenerative, autoimmune, or malignant
      diseases. New data now describe its regulatory effects in tissues or fluids from
      patients with neurological diseases. In this mini-review, we aim to highlight the
      role of TWEAK/Fn14 in modulating NI in multiple sclerosis, neuropsychiatric
      systemic lupus erythematosus, stroke, or glioma. TWEAK/Fn14 can modulate NI by
      activating canonical and non-canonical nuclear factor-kappaB pathways but also by
      stimulating mitogen-activated protein kinase signaling. These downstream
      activations are associated with (i) inflammatory cytokine, chemokine and adhesion
      molecule expression or release, involved in NI propagation, (ii) matrix
      metalloproteinase 9 secretion, implicated in blood-brain barrier disruption and
      tissue remodeling, (iii) astrogliosis and microgliosis, and (iv) migration of
      tumor cells in glioma. In addition, we report several animal and human studies
      pointing to TWEAK as an attractive therapeutic target.

PMID- 29201026
TI  - TH17 Cell Frequency in Peripheral Blood Is Elevated in Overweight Children
      without Chronic Inflammatory Diseases.
AB  - Background: The prevalence of obesity has dramatically increased in children in
      the last few decades and is associated with chronic inflammatory diseases. Fat
      tissue produces IL-6 and TNF-alpha, which are stimuli for TH17 cell
      differentiation. These cells are characterized by expression of the transcription
      factor receptor-related orphan receptor C (RORC) and by IL-17A production. In
      murine models, obesity has been linked with elevated TH17 cell frequencies. The
      aim of this study was to explore whether being overweight was associated with an
      elevated frequency of circulating TH17 cells or elevated messenger RNA (mRNA)
      levels of IL-17A and RORC in children without chronic inflammatory diseases.
      Methods: We studied peripheral blood samples from 15 overweight and 50 non
      overweight children without a history of autoimmune diseases, asthma, atopic
      dermatitis or allergic rhinoconjunctivitis. TH17 cells were quantified in
      Ionomycin stimulated peripheral blood mononuclear cells by flow cytometry using
      intracellular IL-17A staining. RORC- and IL-17A expressions were measured by real
      time PCR. Results: We found significantly elevated TH cell frequencies in
      overweight children compared then on-overweight controls with 34.7 +/- 1.5% of
      CD3+CD4+ cells versus 25.4 +/- 2.4% (mean +/- SEM, p = 0.0023), respectively.
      Moreover, TH cell frequencies correlated positively with body mass index (r =
      0.42, p = 0.0005, respectively). The relative mRNA expression of RORC (p = 0.013)
      and IL-17A (p = 0.014) were upregulated in overweight compared to non-overweight
      children. Conclusion: Childhood obesity is an independent factor that is
      associated with an elevated frequency of circulating TH17 cells and higher
      expression of RORC- and IL-17A-mRNA after in vitro stimulation with Ionomycin.
      This might be due to the inflammatory activity of the fat tissue. Studies on TH17
      immunity should not only be adjusted for acute and chronic inflammatory diseases
      but also for overweight.

PMID- 29201027
TI  - l-Citrulline Metabolism in Mice Augments CD4+ T Cell Proliferation and Cytokine
      Production In Vitro, and Accumulation in the Mycobacteria-Infected Lung.
AB  - Activation, recruitment, and effector function of T lymphocytes are essential for
      control of mycobacterial infection. These processes are tightly regulated in T
      cells by the availability of l-arginine within the microenvironment. In turn,
      mycobacterial infection dampens T cell responsiveness through arginase induction
      in myeloid cells, promoting sequestration of l-arginine within the local milieu.
      Here, we show T cells can replenish intracellular l-arginine through metabolism
      of l-citrulline to mediate inflammatory function, allowing anti-mycobacterial T
      cells to overcome arginase-mediated suppression. Furthermore, T cell l-citrulline
      metabolism is necessary for accumulation of CD4+ T cells at the site of
      infection, suggesting this metabolic pathway is involved during anti
      mycobacterial T cell immunity in vivo. Together, these findings establish a
      contribution for l-arginine synthesis by T cells during mycobacterial infection,
      and implicate l-citrulline as a potential immuno-nutrient to modulate host
      immunity.

PMID- 29201028
TI  - Shaping Innate Lymphoid Cell Diversity.
AB  - Innate lymphoid cells (ILCs) are a key cell type that are enriched at mucosal
      surfaces and within tissues. Our understanding of these cells is growing rapidly.
      Paradoxically, these cells play a role in maintaining tissue integrity but they
      also function as key drivers of allergy and inflammation. We present here the
      most recent understanding of how genomics has provided significant insight into
      how ILCs are generated and the enormous heterogeneity present within the
      canonical subsets. This has allowed the generation of a detailed blueprint for
      ILCs to become highly sensitive and adaptive sensors of environmental changes and
      therefore exquisitely equipped to protect immune surfaces.

PMID- 29201029
TI  - Virologic and Immunologic Characteristics in Mature Ducks with Acute Duck
      Hepatitis A Virus 1 Infection.
AB  - Duck hepatitis A virus 1 (DHAV-1) infection in mature ducks has previously been
      proposed as a small-animal model for human hepatitis A. However, basic research
      on the outcome of DHAV-1 infection in mature ducks is limited. Here, we examined
      the course of viremia, the characteristics of antibody responses, and the
      profiles of plasma cytokines in mature ducks infected with DHAV-1. During the
      course of infection, the viremia was detectable soon after infection and
      persisted for 196 days, however, the ducks presented as clinically asymptomatic.
      Specific and timely immunoglobulin G (IgG), IgM, and IgA1 responses were
      elicited. At the same time, extensive inhibition of viral replication was
      observed with increasing IgG concentration. With respect to pattern-recognition
      receptors, TLR-7 was mainly involved in triggering the innate defense against the
      DHAV-1 infection. In addition, plasma immune analytes were measured and were
      determined to have bidirectional roles in virus clearance. It was concluded that
      DHAV-1 spreads quickly in blood. The spontaneous clearance of DHAV-1 during
      asymptomatic infection in mature ducks depends on the cooperation of timely
      antibody responses and alert innate immune responses. Moreover, the delayed
      clearance may be associated with a weak interferon-gamma-producing CD8+ T cell
      response. This study allows us to reveal the mechanism of clearance and
      persistence of DHAV-1 infection in mature ducks. We anticipate that it will
      provide a basis for future studies focused on defining the nature mechanisms
      involved in the clearance and persistence of human hepatitis virus.

PMID- 29201030
TI  - Toll-Like Receptor 4, but Not Neutrophil Extracellular Traps, Promote IFN Type I
      Expression to Enhance Th2 Responses to Nippostrongylus brasiliensis.
AB  - The induction of Th2 responses is thought to be multifactorial, and emerge from
      specific pathways distinct from those associated with antagonistic antibacterial
      or antiviral Th1 responses. Here, we show that the recognition of non-viable
      Nippostrongylus brasiliensis (Nb) in the skin induces a strong recruitment of
      monocytes and neutrophils and the release of neutrophil extracellular traps
      (NETs). Nb also activates toll-like receptor 4 (TLR4) signaling with expression
      of Ifnb transcripts in the skin and the development of an IFN type I signature on
      helminth antigen-bearing dendritic cells in draining lymph nodes. Co-injection of
      Nb together with about 10,000 Gram-negative bacteria amplified this TLR4
      dependent but NET-independent IFN type I response and enhanced the development of
      Th2 responses. Thus, a limited activation of antibacterial signaling pathways is
      able to boost antihelminthic responses, suggesting a role for bacterial sensing
      in the optimal induction of Th2 immunity.

PMID- 29201032
TI  - W342F Mutation in CCaMK Enhances Its Affinity to Calmodulin But Compromises Its
      Role in Supporting Root Nodule Symbiosis in Medicago truncatula.
AB  - The calcium/calmodulin-dependent protein kinase (CCaMK) is regulated by free Ca2+
      and Ca2+-loaded calmodulin. This dual binding is believed to be involved in its
      regulation and associated physiological functions, although direct experimental
      evidence for this is lacking. Here we document that site-directed mutations in
      the calmodulin-binding domain of CCaMK alters its binding capacity to calmodulin,
      providing an effective approach to study how calmodulin regulates CCaMK in terms
      of kinase activity and regulation of rhizobial symbiosis in Medicago truncatula.
      We observed that mutating the tryptophan at position 342 to phenylalanine (W342F)
      markedly increased the calmodulin-binding capability of the mutant. The mutant
      CCaMK underwent autophosphorylation and catalyzed substrate phosphorylation in
      the absence of calcium and calmodulin. When the mutant W342F was expressed in
      ccamk-1 roots, the transgenic roots exhibited an altered nodulation phenotype.
      These results indicate that altering the calmodulin-binding domain of CCaMK could
      generate a constitutively activated kinase with a negative role in the
      physiological function of CCaMK.

PMID- 29201031
TI  - Age-Associated Changes in Estrogen Receptor Ratios Correlate with Increased
      Female Susceptibility to Coxsackievirus B3-Induced Myocarditis.
AB  - Sexual bias is a hallmark in various diseases. This review evaluates sexual
      dimorphism in clinical and experimental coxsackievirus B3 (CVB3) myocarditis, and
      how sex bias in the experimental disease changes with increased age.
      Coxsackieviruses are major causes of viral myocarditis, an inflammation of the
      heart muscle, which is more frequent and severe in men than women. Young male
      mice infected with CVB3 develop heart-specific autoimmunity and severe
      myocarditis. Females infected during estrus (high estradiol) develop T-regulatory
      cells and when infected during diestrus (low estradiol) develop autoimmunity
      similar to males. During estrus, protection depends on estrogen receptor alpha
      (ERalpha), which promotes type I interferon, activation of natural killer/natural
      killer T cells and suppressor cell responses. Estrogen receptor beta has opposing
      effects to ERalpha and supports pro-inflammatory immunity. However, the sexual
      dimorphism of the disease is significantly ameliorated in aged animals when old
      females become as susceptible as males. This correlates to a selective loss of
      the ERalpha that is required for immunosuppression. Therefore, sex-associated
      hormones control susceptibility in the virus-mediated disease, but their impact
      can alter with the age and physiological stage of the individual.

PMID- 29201033
TI  - Cell-Based Phenotyping Reveals QTL for Membrane Potential Maintenance Associated
      with Hypoxia and Salinity Stress Tolerance in Barley.
AB  - Waterlogging and salinity are two major abiotic stresses that hamper crop
      production world-wide resulting in multibillion losses. Plant abiotic stress
      tolerance is conferred by many interrelated mechanisms. Amongst these, the cell's
      ability to maintain membrane potential (MP) is considered to be amongst the most
      crucial traits, a positive relationship between the ability of plants to maintain
      highly negative MP and its tolerance to both salinity and waterlogging stress.
      However, no attempts have been made to identify quantitative trait loci (QTL)
      conferring this trait. In this study, the microelectrode MIFE technique was used
      to measure the plasma membrane potential of epidermal root cells of 150 double
      haploid (DH) lines of barley (Hordeum vulgare L.) from a cross between a Chinese
      landrace TX9425 and Japanese malting cultivar Naso Nijo under hypoxic conditions.
      A major QTL for the MP in the epidermal root cells in hypoxia-exposed plants was
      identified. This QTL was located on 2H, at a similar position to the QTL for
      waterlogging and salinity tolerance reported in previous studies. Further
      analysis confirmed that MP showed a significant contribution to both waterlogging
      and salinity tolerance. The fact that the QTL for MP was controlled by a single
      major QTL illustrates the power of the single-cell phenotyping approach and opens
      prospects for fine mapping this QTL and thus being more effective in marker
      assisted selection.

PMID- 29201034
TI  - Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana
      tabacum and Enhances Plant Resistance to Ralstonia solanacearum.
AB  - Various classes of plant pathogenesis-related proteins have been identified in
      the past several decades. PR-Q, a member of the PR3 family encoding chitinases,
      has played an important role in regulating plant resistance and preventing
      pathogen infection. In this paper, we functionally characterized NtPR-Q in
      tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87
      resulted in higher resistance to Ralstonia solanacearum inoculation.
      Surprisingly, overexpression of NtPR-Q led to the activation of many defense
      related genes, such as salicylic acid (SA)-responsive genes NtPR1a/c, NtPR2 and
      NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC
      Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress
      responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene
      and methyl jasmonate, which could enhance the resistance of tobacco to R.
      solanacearum. Collectively, our results suggested that NtPR-Q overexpression led
      to the up-regulation of defense-related genes and enhanced plant resistance to R.
      solanacearum infection.

PMID- 29201035
TI  - Effects of EPSPS Copy Number Variation (CNV) and Glyphosate Application on the
      Aromatic and Branched Chain Amino Acid Synthesis Pathways in Amaranthus palmeri.
AB  - A key enzyme of the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate
      synthase (EPSPS; EC 2.5.1.19), is the known target of the widely used herbicide
      glyphosate. Glyphosate resistance in Amaranthus palmeri, one of the most
      troublesome weeds in agriculture, has evolved through increased EPSPS gene copy
      number. The aim of this work was to study the pleiotropic effects of (i) EPSPS
      increased transcript abundance due to gene copy number variation (CNV) and of
      (ii) glyphosate application on the aromatic amino acid (AAA) and branched chain
      amino acid (BCAA) synthesis pathways. Hydroponically grown glyphosate sensitive
      (GS) and glyphosate resistant (GR) plants were treated with glyphosate 3 days
      after treatment. In absence of glyphosate treatment, high EPSPS gene copy number
      had only a subtle effect on transcriptional regulation of AAA and BCAA pathway
      genes. In contrast, glyphosate treatment provoked a general accumulation of the
      transcripts corresponding to genes of the AAA pathway leading to synthesis of
      chorismate in both GS and GR. After chorismate, anthranilate synthase transcript
      abundance was higher while chorismate mutase transcription showed a small
      decrease in GR and remained stable in GS, suggesting a regulatory branch point in
      the pathway that favors synthesis toward tryptophan over phenylalanine and
      tyrosine after glyphosate treatment. This was confirmed by studying enzyme
      activities in vitro and amino acid analysis. Importantly, this upregulation was
      glyphosate dose dependent and was observed similarly in both GS and GR
      populations. Glyphosate treatment also had a slight effect on the expression of
      BCAA genes but no general effect on the pathway could be observed. Taken
      together, our observations suggest that the high CNV of EPSPS in A. palmeri GR
      populations has no major pleiotropic effect on the expression of AAA biosynthetic
      genes, even in response to glyphosate treatment. This finding supports the idea
      that the fitness cost associated with EPSPS CNV in A. palmeri may be limited.

PMID- 29201036
TI  - Nitrogen Deposition Enhances Photosynthesis in Moso Bamboo but Increases
      Susceptibility to Other Stress Factors.
AB  - Atmospheric nitrogen (N) deposition can increase the susceptibility of vascular
      plants to other stresses, but the physiological basis of such a response remains
      poorly understood. This study was designed to clarify the physiological
      mechanisms and to evaluate bioindicators of N deposition impact on vascular
      plants. We evaluate multiple physiological responses to ~4 years of simulated
      additional N deposition (30-90 kg N ha-1 year-1) on three age-classes (1a, 3a,
      and 5a) of Moso bamboo. A saturating response to the additional N deposition was
      found both in foliar N concentration and in Pn. However, 3- and 5-year-old bamboo
      seemed to be less tolerant to extremely high N deposition than 1-year-old bamboo
      since they were saturated at a lower N addition. Furthermore, C/N/P
      stoichiometric ratios were very sensitive to N deposition in all three-age
      classes of bamboo, but the responses to N deposition in the various age-classes
      were diverse. We also found that the highest additional N deposition suppressed
      stomatal conductance and transpiration rate, suggesting an induced water stress.
      The stress induced by the high N load was also seen in photochemistry, where it
      reduced potential and actual photosynthetic use of light energy, diminished photo
      protection capacity, and increased risk of the photo-damage. High additional N
      deposition contributed to a decrease in the foliar soluble protein contents and
      to an increase in the peroxidase activity (POD). Our study suggested, for the
      first time, that although the photosynthetic rate was enhanced by the increased N
      deposition in Moso bamboo, long-term high N load causes negative effects, such as
      damage to photosystem II. In Moso bamboo photochemical parameters are more
      sensitive to N deposition than photosynthetic rate or foliar N concentration.
      Furthermore, plant age should be taken into account when assessing plants'
      susceptibility to changes in global change drivers, such as N deposition. These
      findings facilitate the revealing of the risks potentially caused to vascular
      plants by increased N deposition before any visible symptoms of injury are seen.

PMID- 29201037
TI  - Transcriptomic Response of Resistant (PI613981-Malus sieversii) and Susceptible
      ("Royal Gala") Genotypes of Apple to Blue Mold (Penicillium expansum) Infection.
AB  - Malus sieversii from Central Asia is a progenitor of the modern domesticated
      apple (Malus * domestica). Several accessions of M. sieversii are highly
      resistant to the postharvest pathogen Penicillium expansum. A previous study
      identified the qM-Pe3.1 QTL on LG3 for resistance to P. expansum in the mapping
      population GMAL4593, developed using the resistant accession, M. sieversii 
      PI613981, and the susceptible cultivar "Royal Gala" (RG) (M. domestica), as
      parents. The goal of the present study was to characterize the transcriptomic
      response of susceptible RG and resistant PI613981 apple fruit to wounding and
      inoculation with P. expansum using RNA-Seq. Transcriptomic analyses 0-48 h post
      inoculation suggest a higher basal level of resistance and a more rapid and
      intense defense response to wounding and wounding plus inoculation with P.
      expansum in M. sieversii -PI613981 than in RG. Functional analysis showed that
      ethylene-related genes and genes involved in "jasmonate" and "MYB-domain
      transcription factor family" were over-represented in the resistant genotype. It
      is suggested that the more rapid response in the resistant genotype (Malus
      sieversii-PI613981) plays a major role in the resistance response. At least
      twenty DEGs were mapped to the qM-Pe3.1 QTL (M * d v.1: 26,848,396-28,424,055) on
      LG3, and represent potential candidate genes responsible for the observed
      resistance QTL in M. sieversii-PI613981. RT-qPCR of several of these genes was
      used to validate the RNA-Seq data and to confirm their higher expression in MS0.

PMID- 29201039
TI  - Multitemporal Volume Registration for the Analysis of Rheumatoid Arthritis
      Evolution in the Wrist.
AB  - This paper describes a method based on an automatic segmentation process to
      coregister carpal bones of the same patient imaged at different time points. A
      rigid registration was chosen to avoid artificial bone deformations and to allow
      finding eventual differences in the bone shape due to erosion, disease
      regression, or other eventual pathological signs. The actual registration step is
      performed on the basis of principal inertial axes of each carpal bone volume, as
      estimated from the inertia matrix. In contrast to already published approaches,
      the proposed method suggests splitting the 3D rotation into successive rotations
      about one axis at a time (the so-called basic or elemental rotations). In such a
      way, singularity and ambiguity drawbacks affecting other classical methods, for
      instance, the Euler angles method, are addressed. The proposed method was
      quantitatively evaluated using a set of real magnetic resonance imaging (MRI)
      sequences acquired at two different times from healthy wrists and by choosing a
      direct volumetric comparison as a cost function. Both the segmentation and
      registration steps are not based on a priori models, and they are therefore able
      to obtain good results even in pathological cases, as proven by the visual
      evaluation of actual pathological cases.

PMID- 29201038
TI  - Anatomical Alterations in Plant Tissues Induced by Plant-Parasitic Nematodes.
AB  - Plant-parasitic nematodes (PPNs) interact with plants in different ways, for
      example, through subtle feeding behavior, migrating destructively through
      infected tissues, or acting as virus-vectors for nepoviruses. They are all
      obligate biotrophic parasites as they derive their nutrients from living cells
      which they modify using pharyngeal gland secretions prior to food ingestion. Some
      of them can also shield themselves against plant defenses to sustain a relatively
      long lasting interaction while feeding. This paper is centered on cell types or
      organs that are newly induced in plants during PPN parasitism, including recent
      approaches to their study based on molecular biology combined with cell biology
      histopathology. This issue has already been reviewed extensively for major PPNs
      (i.e., root-knot or cyst nematodes), but not for other genera (viz. Nacobbus
      aberrans, Rotylenchulus spp.). PPNs have evolved with plants and this co
      evolution process has allowed the induction of new types of plant cells necessary
      for their parasitism. There are four basic types of feeding cells: (i) non
      hypertrophied nurse cells; (ii) single giant cells; (iii) syncytia; and (iv)
      coenocytes. Variations in the structure of these cells within each group are also
      present between some genera depending on the nematode species viz. Meloidogyne or
      Rotylenchulus. This variability of feeding sites may be related in some way to
      PPN life style (migratory ectoparasites, sedentary ectoparasites, migratory ecto
      endoparasites, migratory endoparasites, or sedentary endoparasites). Apart from
      their co-evolution with plants, the response of plant cells and roots are closely
      related to feeding behavior, the anatomy of the nematode (mainly stylet size,
      which could reach different types of cells in the plant), and the secretory
      fluids produced in the pharyngeal glands. These secretory fluids are injected
      through the stylet into perforated cells where they modify plant cytoplasm prior
      to food removal. Some species do not produce specialized feeding sites (viz.
      Ditylenchus, Subanguina), but may develop a specialized modification of the root
      system (e.g., unspecialized root galls or a profusion of roots). This review
      introduces new data on cell types and plant organs stimulated by PPNs using
      sources varying from traditional histopathology to new holistic methodologies.

PMID- 29201040
TI  - Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates
      Nonalcoholic Fatty Liver through the Regulation of PPARdelta and Adiponectin in
      ApoE KO Mice.
AB  - Aster glehni is well known for its therapeutic properties. This study was
      performed to investigate the effects of A. glehni on nonalcoholic fatty liver
      disease (NAFLD) in atherosclerotic condition, by determining the levels of
      biomarkers related to lipid metabolism and inflammation in serum, liver, and
      adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride
      level decreased in all groups treated with A. glehni. Serum adiponectin
      concentration and protein levels of peroxisome proliferator-activated receptor
      delta, 5' adenosine monophosphate-activated protein kinase, acetyl-CoA
      carboxylase, superoxide dismutase, and PPARgamma coactivator 1-alpha in liver
      tissues increased in the groups treated with A. glehni. Conversely, protein
      levels of ATP citrate lyase, fatty acid synthase, tumor necrosis factor alpha,
      and 3-hydroxy-3-methylglutaryl-CoA reductase and the concentrations of
      interleukin 6 and reactive oxygen species decreased upon A. glehni. Triglyceride
      concentration in the liver was lower in mice treated with A. glehni than in
      control mice. Lipid accumulation in HepG2 and 3T3-L1 cells decreased upon A.
      glehni treatment; this effect was suppressed in the presence of the PPARdelta
      antagonist, GSK0660. Our findings suggest that A. glehni extracts may ameliorate
      NAFLD through regulation of PPARdelta, adiponectin, and the related subgenes.

PMID- 29201041
TI  - Decoding of Human Movements Based on Deep Brain Local Field Potentials Using
      Ensemble Neural Networks.
AB  - Decoding neural activities related to voluntary and involuntary movements is
      fundamental to understanding human brain motor circuits and neuromotor disorders
      and can lead to the development of neuromotor prosthetic devices for
      neurorehabilitation. This study explores using recorded deep brain local field
      potentials (LFPs) for robust movement decoding of Parkinson's disease (PD) and
      Dystonia patients. The LFP data from voluntary movement activities such as left
      and right hand index finger clicking were recorded from patients who underwent
      surgeries for implantation of deep brain stimulation electrodes. Movement-related
      LFP signal features were extracted by computing instantaneous power related to
      motor response in different neural frequency bands. An innovative neural network
      ensemble classifier has been proposed and developed for accurate prediction of
      finger movement and its forthcoming laterality. The ensemble classifier contains
      three base neural network classifiers, namely, feedforward, radial basis, and
      probabilistic neural networks. The majority voting rule is used to fuse the
      decisions of the three base classifiers to generate the final decision of the
      ensemble classifier. The overall decoding performance reaches a level of
      agreement (kappa value) at about 0.729 +/- 0.16 for decoding movement from the
      resting state and about 0.671 +/- 0.14 for decoding left and right visually cued
      movements.

PMID- 29201042
TI  - Adaptive Compressive Sensing of Images Using Spatial Entropy.
AB  - Compressive Sensing (CS) realizes a low-complex image encoding architecture,
      which is suitable for resource-constrained wireless sensor networks. However, due
      to the nonstationary statistics of images, images reconstructed by the CS-based
      codec have many blocking artifacts and blurs. To overcome these negative effects,
      we propose an Adaptive Block Compressive Sensing (ABCS) system based on spatial
      entropy. Spatial entropy measures the amount of information, which is used to
      allocate measuring resources to various regions. The scheme takes spatial entropy
      into consideration because rich information means more edges and textures. To
      reduce the computational complexity of decoding, a linear mode is used to
      reconstruct each block by the matrix-vector product. Experimental results show
      that our ABCS coding system provides a better reconstruction quality from both
      subjective and objective points of view, and it also has a low decoding
      complexity.

PMID- 29201044
TI  - Ischaemic Preconditioning Suppresses Necrosis of Adipocutaneous Flaps in a
      Diabetic Rat Model Regardless of the Manner of Preischaemia Induction.
AB  - Ischaemic insult in the skin flaps is a major problem in reconstructive surgery
      particularly in patients with diabetes mellitus. Here, we sought to investigate
      the effectiveness of ischaemic preconditioning (IP) on diabetic skin flaps in rat
      animal model. Hundred Wistar rats (90 streptozotocin treated animals and 10
      nondiabetic controls) were used. Diabetes mellitus was confirmed by measuring
      glucose level in blood, HbA1c, and ketonuria. We used blood vessel clamping, hind
      limb tourniquet, and NO donors (Spermine/NO complex) to induce short-term
      ischaemia of tissues that will be excised for skin flaps. Animals were followed
      for 5 days. Flaps were photographed at day 5 and percent of necrosis was
      determined using planimetry. Significant decrease in percent of necrotic tissue
      in all groups that received preconditioning was observed. Results show that
      ischaemic preconditioning suppresses flap necrosis in diabetic rats irrespective
      of direct or remote tissue IP and irrespective of chemically or physically
      induced preischaemia. Spermine/NO complex treatment 10 minutes after the flap
      ischaemia suppressed tissue necrosis. Treatment with NO synthase inhibitor L-NAME
      reversed effects of IP showing importance of NO for this process. We show that IP
      is a promising approach for suppression of tissue necrosis in diabetic flaps and
      potential of NO pathway as therapeutic target in diabetic flaps.

PMID- 29201043
TI  - Clinical and Genetic Review of Hereditary Acral Reticulate Pigmentary Disorders.
AB  - Reticulated pigmentation is a unique pigmentary change caused by a heterogeneous
      group of hereditary and acquired disorders. This pigmentation is characterized by
      a mottled appearance, with lesions that vary in size and pigmentary content. This
      review discusses the hereditary group of the reticulated pigmentation disorders,
      such as dyschromatosis symmetrica hereditaria, dyschromatosis universalis
      hereditaria, and reticulate acropigmentation of Kitamura. The clinical
      presentation and histopathological features often overlap, making diagnosis
      difficult. However, each of these hereditary conditions possesses a unique
      genetic mutation, and genetic analysis is thus more useful in the diagnosis of
      these conditions. This article delivers an update regarding the clinical
      features, detailed histopathological description, and genetic information
      concerning hereditary reticulate pigmentary disorders and aims to provide useful
      background for use by clinical dermatologists and histopathologists when
      approaching this group of hereditary disorders.

PMID- 29201045
TI  - Functional Bowel Disorders Are Associated with a Central Immune Activation.
AB  - Background: Subjects with depression and unexplained neurological symptoms have a
      high prevalence of gastrointestinal comorbidity probably related to the brain-gut
      communication. This study explored associations between functional
      gastrointestinal disorders (FGID) and inflammatory markers in subjects with these
      disorders. Methods: The FGID, including irritable bowel syndrome (IBS), were
      classified according to the Rome III criteria, and degree of symptoms was
      assessed with IBS symptom severity score (IBS-SSS). A range of interleukins (IL),
      chemokines and growth factors, tryptophan, and kynurenine were analysed in serum
      and the cerebrospinal fluid (CSF), and short-chain fatty acids (SCFA) were
      analysed in the faeces. The results are reported as partial correlation (pc) and
      p values. Results: Sixty-six subjects were included. IBS was associated with high
      levels of tryptophan (p = 0.048) and kynurenine (p = 0.019) and low level of IL
      10 (p = 0.047) in the CSF. IBS-SSS was associated with high tumor necrosis factor
      and low IL-10 in the CSF; pc = 0.341 and p = 0.009 and pc = -0.299 and p = 0.023,
      respectively. Propionic minus butyric acid in faeces was negatively associated
      with IL-10 in the CSF (pc = -0.416, p = 0.005). Conclusions: FGID were associated
      with a proinflammatory immune activation in the central nervous system and a
      disturbed tryptophan metabolism that could have been mediated by the faecal
      microbiota.

PMID- 29201046
TI  - Parallel Changes in Harvey-Bradshaw Index, TNFalpha, and Intestinal Fatty Acid
      Binding Protein in Response to Infliximab in Crohn's Disease.
AB  - : Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity.
      AIMS: determine if I-FABP is elevated in active Crohn's disease (CD) and if I
      FABP parallels anti-TNFalpha antibody (infliximab) induced lowering of TNFalpha
      and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP
      distribution along human gut was determined. Serum from 10 CD patients collected
      during first three consecutive infliximab treatments with matched pretreatment
      and follow-up samples one week after each treatment and corresponding HBI data
      were analyzed. I-FABP reference interval was established from 31 healthy subjects
      with normal gut permeability. I-FABP and TNFalpha were measured by ELISA; CRP was
      measured by nephelometry. Healthy tissue was used for I-FABP
      immunohistochemistry. Pretreatment CD patient TNFalpha was 1.6-fold higher than
      in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at
      follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I
      FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in
      epithelium of stomach, jejunum, ileum, and colon, with the highest expression in
      jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to
      TNFalpha. Parallel infliximab effects on TNFalpha, HBI, and I-FABP were found. I
      FABP may be useful as an intestine selective prognostic marker in CD.

PMID- 29201047
TI  - Pulmonary Complications after Surgery for Rectal Cancer in Elderly Patients:
      Evaluation of Laparoscopic versus Open Approach from a Multicenter Study on 477
      Consecutive Cases.
AB  - Aim: To evaluate the impact of open or laparoscopic rectal surgery on pulmonary
      complications in elderly (>75 years old) patients. Methods: Data from consecutive
      patients who underwent elective laparoscopic or open rectal surgery for cancer
      were collected prospectively from 3 institutions. Pulmonary complications were
      defined according to the ACS/NSQUIP definition. Results: A total of 477 patients
      (laparoscopic group: 242, open group: 235) were included in the analysis.
      Postoperative pulmonary complications were significantly more common after open
      surgery (8 out of 242 patients (3.3%) versus 23 out of 235 patients (9.8%); p =
      0.005). In addition, PPC occurrence was associated with the increasing of
      postoperative pain (5.04 +/- 1.62 versus 5.03 +/- 1.58; p = 0.001) and the
      increasing of operative time (270.06 +/- 51.49 versus 237.37 +/- 65.97; p =
      0.001). Conclusion: Our results are encouraging to consider laparoscopic surgery
      a safety and effective way to treat rectal cancer in elderly patients,
      highlighting that laparoscopic surgery reduces the occurrence of postoperative
      pulmonary complications.

PMID- 29201048
TI  - Drug Errors and Protocol for Prevention among Anaesthetists in Nigeria.
AB  - Background: Drugs are often prescribed, dispensed, and administered by the same
      person during anaesthesia, and this may increase the risk of drug error.
      Objectives: To assess the frequency of drug administration errors by
      anaesthetists, the drugs commonly involved, and the effects of such errors.
      Method: A questionnaire-based study was carried out among participants at an
      annual conference of Nigerian anaesthetists. Sixty-six of the 80 participants
      returned the completed questionnaire. The respondents comprised 1 nurse
      anaesthetist, 34 resident doctors, 3 doctors with diploma in anaesthesia, and 28
      consultant anaesthetists. The collated data on drug errors, the effect of such
      errors on patients, and formulated protocols to prevent future occurrence were
      subjected to descriptive analysis using Microsoft Excel. Result: Drug error was
      reported by 71.21% and witnessed by 22.72% of the respondents. Most of the drug
      errors occurred during general anaesthesia (90.3%) for emergency procedures
      (51.61%), and muscle relaxants were most commonly involved (58.06%). Conclusion:
      Drug errors are common among anaesthetists in Nigeria and their incidence is
      greater during general anaesthesia for emergency procedures, largely as a result
      of ampoule swaps due to similarities in ampoule design and packaging. Guidelines
      on their prevention should be developed by all health institutions.

PMID- 29201049
TI  - Metals in Fishes from Yongshu Island, Southern South China Sea: Human Health Risk
      Assessment.
AB  - In order to assess the bioaccumulation of metals associated with gender, tissues,
      and their potential ecological risk, four species of fish were collected from the
      Yongshu Island in the Southern South China Sea. Metals and stable Pb isotopes in
      their tissues (muscle, gill, liver, intestine, and ovary) were determined. The
      concentrations of metals (mg/kg, dry weight) in these species were ND-21.60 (Cd),
      1.21-4.87 (Cr), 0.42-22.4 (Cu), 1.01-51.8 (Mn), 0.30-3.28 (Ni), 6.04-1.29 * 103
      (Zn), 14.89-1.40 * 103 (Fe), and 0.22-3.36 (Pb). In general, the liver and
      intestine absorbed more metals than the other tissues. Metals accumulation can be
      influenced by gender and feeding behavior and in fact, female fish and dietary
      exposure are more prone to accumulate metals. In addition, Pb isotopic ratios
      indicated that all species had significant biological fractionation, which may
      not make them good tracers for source identification. The metal concentrations of
      most samples were lower than the national standard values of the FAO (USA), which
      suggested that human consumption of these species may not cause health risks.
      However, since the surrounding areas are developing rapidly, the potential
      environmental risk of metals will intensify and should receive more attention.

PMID- 29201050
TI  - The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of
      Both Parameters Affected by Deltamethrin and Methomyl Exposure.
AB  - The unpredictable toxicity of insecticides may cause behavior disorder of
      biological organisms. In order to assess the role of acetylcholinesterase (AChE)
      in swimming behavior of Daphnia magna, a correlation analysis of both parameters
      in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The
      behavior responses of D. magna in DM (13.36 MUg/L and 33.40 MUg/L) and MT (19.66
      MUg/L and 49.15 MUg/L) suggested that recovery behavior in the adjustment phase
      was crucial, and behavior homeostasis provided them with an optimal way to
      achieve a wider tolerance against environmental stress. During the experiment,
      positive effects on AChE activity occurred in the beginning of the exposure. Even
      though the de novo synthesis of AChE in D. magna might help it recover, the AChE
      inhibition in different treatments could be observed. Some induction effects on
      AChE activity at the beginning of exposure occurred, and a 50% decrease may cause
      toxic effects on behavior. In most treatments, the results showed that both
      behavior strength and AChE activity stayed in the same field within a correlation
      circle. These results illustrated that the environmental stress caused by both DM
      and MT could inhibit AChE activity and subsequently induce a stepwise behavior
      response, though both pesticides affect it as direct and indirect inhibitors,
      respectively.

PMID- 29201051
TI  - Psychometric Properties of Diabetes Management Self-Efficacy in Thai Type 2
      Diabetes Mellitus Patients: A Multicenter Study.
AB  - Objective: The aims of this study were to translate and psychometrically evaluate
      the Thai version of diabetes management self-efficacy scale (T-DMSES) and to
      examine its association with HbA1c control in diabetic individuals. Methods: This
      study recruited patients from outpatient diabetes clinics of both community and
      university hospitals. The first phases of this study involved translation of the
      existing DMSES into Thai, and in the second phase, we evaluated its psychometric
      properties. The construct validity was evaluated using confirmatory factor
      analysis. Criterion validity of DMSES was subsequently evaluated by examining
      DMSES's association with HbA1c control. Results: The T-DMSES contains 20 items
      across four factors. Confirmatory factor analysis demonstrated the construct
      validity of T-DMSES (chi2 = 645.142, df = 164, p < 0.001, CFI = 0.98, RMSEA =
      0.065, TLI = 0.977, and AGFI = 0.981). The T-DMSES was also shown to be criterion
      valid with most subscales highly associated with HbA1c control. Conclusion: The T
      DMSES was shown to have good psychometric properties. It is likely to provide
      valuable insights into the epidemiology of diabetes management self-efficacy and
      may also prove useful in evaluating interventions for raising diabetes management
      self-efficacy, which in turn, improve both patient self-management and blood
      sugar control.

PMID- 29201052
TI  - Rapid Action of Aldosterone on Protein Levels of Sodium-Hydrogen Exchangers and
      Protein Kinase C Beta Isoforms in Rat Kidney.
AB  - Previous in vitro studies demonstrated that aldosterone rapidly activates sodium
      hydrogen exchangers 1 and 3 (NHE 1 and 3). In vitro investigations revealed that
      protein kinase C (PKC) regulates NHE properties. We previously demonstrated that
      aldosterone rapidly enhances PKCalpha protein abundance in the rat kidney. There
      are no reports of renal PKCbeta (I and II) protein levels related to the
      regulation by aldosterone. There are also no in vivo data regarding the rapid
      effects of aldosterone on renal protein levels of NHE (1 and 3) and PKCbeta (I
      and II), simultaneously. In the current study, rats received normal saline
      solution or aldosterone (150 MUg/kg BW, i.p.). After 30 minutes, abundance and
      immunoreactivity of these proteins were determined by Western blot analysis and
      immunohistochemistry, respectively. Aldosterone increased NHE1 and NHE3 protein
      abundance to 152% and 134%, respectively (P < 0.05). PKCbetaI protein level was
      enhanced by 30%, whereas PKCbetaII declined slightly. Aldosterone increased NHE
      protein expression mostly in the medulla. PKCbetaI immunostaining intensity was
      increased in the glomeruli, renal vasculature, and thin limb of the loop of
      Henle, while PKCbetaII was reduced. This is the first in vivo study to
      simultaneously demonstrate that aldosterone rapidly elevates PKCbetaI and NHE (1
      and 3) protein abundance in the rat kidney. Aldosterone-induced NHE (1 and 3)
      protein levels may be related to PKCbetaI activation.

PMID- 29201053
TI  - Superfast Set, Strong and Less Degradable Mineral Trioxide Aggregate Cement.
AB  - Purpose: Despite the good sealing ability and biocompatibility of mineral
      trioxide aggregate (MTA), its slow setting, high degradation, and weakness limit
      its use in surgical endodontics and high stress-bearing areas. This study aimed
      to develop two new liquids to control these drawbacks. They were prepared from
      calcium chloride, fumed silica, and hydroxyapatite or calcium phosphate and coded
      "H" and "P," respectively. Methods: Portland cement, Grey ProRoot(r) MTA, and
      white ProRoot MTA were mixed with distilled water (control) or liquid "H" or "P."
      The pH, setting time, degradation rate, leachant/precipitate' composition,
      compressive strength, and morphology were assessed. Results: Both liquids
      maintained MTA's high alkalinity and reduced the setting time by 1-2 orders of
      magnitude. Both liquids, H in particular, significantly reduced the degradation
      rate of Grey ProRoot and White ProRoot MTA(r). Calcite has been identified as the
      main phase of the leachant or precipitate formed during the cement's degradation.
      Calcium hydroxide or hydroxyapatite was also identified with Grey ProRoot MTA
      mixed with H liquid. These liquids also significantly increased the compressive
      strength with no statistical differences between them; this was associated with
      the production of dense, consolidated structures. Conclusions: The modified MTA
      could be used in surgical endodontics and high stress-bearing areas.

PMID- 29201054
TI  - Antibacterial Effects of Natural Herbal Extracts on Streptococcus mutans: Can
      They Be Potential Additives in Dentifrices?
AB  - Background: Many plants or herbs exhibit potent antimicrobial activity against
      various microorganisms. They have no side effects and presumably act against and
      modulate the factors that are crucial for microbial survival or their activity.
      Streptococcus mutans is a pioneer bacteria implicated in dental caries. This
      study aims to evaluate the antimicrobial activity of garlic bulbs, pudina leaves,
      and mango and eucalyptus twig extracts on Streptococcus mutans by evaluating
      their zone of inhibition and determining their minimum inhibitory concentration
      (MIC). Methods: Microbiological assay (well diffusion method) to determine zone
      of inhibition against pure forms of Streptococcus mutans was performed. The
      antibacterial effects of methanolic extracts of mango twigs, eucalyptus twigs,
      pudina leaves, and garlic bulbs were studied. Test compounds were further
      evaluated for their MIC. Results: Extracts derived from mango and eucalyptus
      twigs showed significant antibacterial effects at test concentrations. Pudina and
      garlic extracts did not show any significant antibacterial effects at similar
      concentrations. Upon further evaluation of the 2 positive compounds for their
      MIC, mango twigs demonstrated more antimicrobial potential than eucalyptus twigs
      at a lower concentration. Conclusion: Our observations indicated that the mango
      twig extracts possess higher antibacterial effects against Streptococcus mutans
      than other compounds at specific test concentration.

PMID- 29201055
TI  - Comparison of Attenuated Total Reflectance Mid-Infrared, Near Infrared, and 1H
      Nuclear Magnetic Resonance Spectroscopies for the Determination of Coffee's
      Geographical Origin.
AB  - The sensorial properties of Colombian coffee are renowned worldwide, which is
      reflected in its market value. This raises the threat of fraud by adulteration
      using coffee grains from other countries, thus creating a demand for robust and
      cost-effective methods for the determination of geographical origin of coffee
      samples. Spectroscopic techniques such as Nuclear Magnetic Resonance (NMR), near
      infrared (NIR), and mid-infrared (mIR) have arisen as strong candidates for the
      task. Although a body of work exists that reports on their individual
      performances, a faithful comparison has not been established yet. We evaluated
      the performance of 1H-NMR, Attenuated Total Reflectance mIR (ATR-mIR), and NIR
      applied to fraud detection in Colombian coffee. For each technique, we built
      classification models for discrimination by species (C. arabica versus C.
      canephora (or robusta)) and by origin (Colombia versus other C. arabica) using a
      common set of coffee samples. All techniques successfully discriminated samples
      by species, as expected. Regarding origin determination, ATR-mIR and 1H-NMR
      showed comparable capacity to discriminate Colombian coffee samples, while NIR
      fell short by comparison. In conclusion, ATR-mIR, a less common technique in the
      field of coffee adulteration and fraud detection, emerges as a strong candidate,
      faster and with lower cost compared to 1H-NMR and more discriminating compared to
      NIR.

PMID- 29201056
TI  - Development of a Rapid and Simple Method to Remove Polyphenols from Plant
      Extracts.
AB  - Polyphenols are secondary metabolites of plants, which are responsible for
      prevention of many diseases. Polyvinylpolypyrrolidone (PVPP) has a high affinity
      towards polyphenols. This method involves the use of PVPP column to remove
      polyphenols under centrifugal force. Standards of gallic acid, epigallocatechin
      gallate, vanillin, and tea extracts (Camellia sinensis) were used in this study.
      PVPP powder was packed in a syringe with different quantities. The test samples
      were layered over the PVPP column and subjected to centrifugation. Supernatant
      was tested for the total phenol content. The presence of phenolic compounds and
      caffeine was screened by HPLC and measuring the absorbance at 280. The
      antioxidant capacity of standards and tea extracts was compared with the
      polyphenol removed fractions using DPPH scavenging assay. No polyphenols were
      found in polyphenolic standards or tea extracts after PVPP treatment. The method
      described in the present study to remove polyphenols is simple, inexpensive,
      rapid, and efficient and can be employed to investigate the contribution of
      polyphenols present in natural products to their biological activity.

PMID- 29201057
TI  - Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in
      Cryopreservation of Tissue-Engineered Constructs.
AB  - It is documented that human mesenchymal stem cells (hMSCs) can be differentiated
      into various types of cells to present a tool for tissue engineering and
      regenerative medicine. Thus, the preservation of stem cells is a crucial factor
      for their effective long-term storage that further facilitates their continuous
      supply and transportation for application in regenerative medicine.
      Cryopreservation is the most important, practicable, and the only established
      mechanism for long-term preservation of cells, tissues, and organs, and
      engineered tissues; thus, it is the key step for the improvement of tissue
      engineering. A significant portion of MSCs loses cellular viability while freeze
      thawing, which represents an important technical limitation to achieving
      sufficient viable cell numbers for maximum efficacy. Several natural and
      synthetic materials are extensively used as substrates for tissue engineering
      constructs and cryopreservation because they promote cell attachment and
      proliferation. Rho-associated kinase (ROCK) inhibitors can improve the
      physiological function and postthaw viability of cryopreserved MSCs. This review
      proposes a crosstalk between substrate topology and interaction of cells with
      ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the
      presence of an external electrical field improves the generation of ROCK
      inhibitors to safeguard cellular viability for the enhanced cryopreservation of
      engineered tissues.

PMID- 29201058
TI  - Comparing Circadian Dynamics in Primary Derived Stem Cells from Different Sources
      of Human Adult Tissue.
AB  - Optimising cell/tissue constructs so that they can be successfully accepted and
      integrated within a host body is essential in modern tissue engineering. To do
      this, adult stem cells are frequently utilised, but there are many aspects of
      their environment in vivo that are not completely understood. There is evidence
      to suggest that circadian rhythms and daily circadian temporal cues have
      substantial effects on stem cell activation, cell cycle, and differentiation. It
      was hypothesised that the circadian rhythm in human adult stem cells differs
      depending on the source of tissue and that different entraining signals exert
      differential effects depending on the anatomical source. Dexamethasone and
      rhythmic mechanical stretch were used to synchronise stem cells derived from the
      bone marrow, tooth dental pulp, and abdominal subcutaneous adipose tissue, and it
      was experimentally evidenced that these different stem cells differed in their
      circadian clock properties in response to different synchronisation mechanisms.
      The more primitive dental pulp-derived stem cells did not respond as well to the
      chemical synchronisation but showed temporal clock gene oscillations following
      rhythmic mechanical stretch, suggesting that incorporating temporal circadian
      information of different human adult stem cells will have profound implications
      in optimising tissue engineering approaches and stem cell therapies.

PMID- 29201059
TI  - A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic
      Stroke.
AB  - Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery
      from ischemic stroke. Understanding the role of endogenous neural stem and
      progenitor cells under normal physiological conditions aids in analyzing their
      effects after ischemic injury, including their impact on functional recovery and
      neurogenesis at the site of injury. Recent animal studies have utilized unique
      subsets of exogenous and endogenous stem cells as well as preconditioning with
      pharmacologic agents to better understand the best situation for stem cell
      proliferation, migration, and differentiation. These stem cell therapies provide
      a promising effect on stimulation of endogenous neurogenesis, neuroprotection,
      anti-inflammatory effects, and improved cell survival rates. Clinical trials
      performed using various stem cell types show promising results to their safety
      and effectiveness on reducing the effects of ischemic stroke in humans. Another
      important aspect of stem cell therapy discussed in this review is tracking
      endogenous and exogenous NSCs with magnetic resonance imaging. This review
      explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy
      studies and their effects on neurogenesis, the most recent clinical trials, and
      techniques to track and monitor the progress of endogenous and exogenous stem
      cells.

PMID- 29201060
TI  - Osteogenic Differentiation of hDPSCs on Biogenic Bone Apatite Thin Films.
AB  - A previous study reported the structural characterization of biogenic apatite
      (BAp) thin films realized by a pulsed electron deposition system by ablation of
      deproteinized bovine bone. Thin films annealed at 400 degrees C exhibited
      composition and crystallinity degree very close to those of biogenic apatite;
      this affinity is crucial for obtaining faster osseointegration compared to
      conventional, thick hydroxyapatite (HA) coatings, for both orthopedics and
      dentistry. Here, we investigated the adhesion, proliferation, and osteogenic
      differentiation of human dental pulp stem cells (hDPCS) on as-deposited and heat
      treated BAp and stoichiometric HA. First, we showed that heat-treated BAp films
      can significantly promote hDPSC adhesion and proliferation. Moreover, hDPSCs,
      while initially maintaining the typical fibroblast-like morphology and stemness
      surface markers, later started expressing osteogenic markers such as Runx-2 and
      OSX. Noteworthy, when cultured in an osteogenic medium on annealed BAp films,
      hDPSCs were also able to reach a more mature and terminal commitment, with
      respect to HA and as-deposited films. Our findings suggest that annealed BAp
      films not only preserve the typical biological properties of stemness of, hDPSCs
      but also improve their ability of osteogenic commitment.

PMID- 29201061
TI  - Selective and Irreversible Induction of Necroptotic Cell Death in Lung
      Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib.
AB  - The presence of highly resistant cancer cells and the toxicity to normal cells
      are key factors that limit chemotherapy. Here, we used two models of highly
      resistant lung cancer cells: (1) adherent cells growing under prolonged periods
      of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs)
      to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF).
      Compared to cells growing under routine culture conditions (RCCs), PPPS cells or
      FTs were highly sensitive to short-term exposure (24 h) to VP 100 MUM + SF 5 MUM
      (VP100 + SF5). Recovery experiments exposing cells to VP100 + SF5 for 24 h
      followed by incubation in drug-free media for 48 h demonstrated that while PPSS
      as well as FT cells were unable to recover, cancer cells and the noncancerous
      cell line Beas-2B growing under RCCs were less sensitive and were also able to
      recover significantly. VP100 + SF5 induced significant changes in the expression
      of protein associated with apoptosis, autophagy, and to a lesser extent
      necroptosis. Coincubation experiments with z-VAD-FMK, necrostatin 1, or
      chloroquine showed evidence that necroptosis played a central role. Our data
      demonstrates that highly resistant cancer cells can be selectively eliminated by
      VP + SF and that necroptosis plays a central role.

PMID- 29201062
TI  - Comparative Analysis of Spontaneous and Stimulus-Evoked Calcium Transients in
      Proliferating and Differentiating Human Midbrain-Derived Stem Cells.
AB  - Spontaneous cytosolic calcium transients and oscillations have been reported in
      various tissues of nonhuman and human origin but not in human midbrain-derived
      stem cells. Using confocal microfluorimetry, we studied spontaneous calcium
      transients and calcium-regulating mechanisms in a human ventral mesencephalic
      stem cell line undergoing proliferation and neuronal differentiation. Spontaneous
      calcium transients were detected in a large fraction of both proliferating (>50%)
      and differentiating (>55%) cells. We provide evidence for the existence of
      intracellular calcium stores that respond to muscarinic activation of the cells,
      having sensitivity for ryanodine and thapsigargin possibly reflecting IP3
      receptor activity and the presence of ryanodine receptors and calcium ATPase
      pumps. The observed calcium transient activity potentially supports the existence
      of a sodium-calcium antiporter and the existence of calcium influx induced by
      depletion of calcium stores. We conclude that the cells have developed the most
      important mechanisms governing cytosolic calcium homeostasis. This is the first
      comparative report of spontaneous calcium transients in proliferating and
      differentiating human midbrain-derived stem cells that provides evidence for the
      mechanisms that are likely to be involved. We propose that the observed
      spontaneous calcium transients may contribute to mechanisms involved in cell
      proliferation, phenotypic differentiation, and general cell maturation.

PMID- 29201063
TI  - Malnutrition and Its Associated Factors among Rural School Children in Fayoum
      Governorate, Egypt.
AB  - Malnutrition is an increasing health problem among children in developing
      countries. We assessed the level of malnutrition and associated factors among
      school children in a rural setting in Fayoum Governorate, Egypt. A school based
      cross-sectional survey was conducted on children (6-17 years) in Manshit El Gamal
      village in Tamia district of Fayoum Governorate. Weight, height, and age data
      were used to calculate z-scores of the three nutritional indicators using WHO
      anthroPlus. Sociodemographics and lifestyles Data were collected. Prevalence of
      stunting, underweight, and wasting was 34.2%, 3.4%, and 0.9%, respectively, while
      obesity was 14.9%. Prevalence of obesity was significantly higher in younger age
      group of 6-9 years in comparison with older age and was higher in males versus
      females in 10-13-year-age group. Increasing age, reduced poultry consumption, and
      escaping breakfast were associated factors for stunting with OR (95% CI) 1.27
      (1.17-1.37), 2.19 (1.4-3.4), and 2.3 (1.07-5.03). Younger age and regular
      employment of the father were factors associated with obesity (OR = 0.753; 0.688
      0.824 and OR = 2.217; 1.4-3.5). Malnutrition is highly prevalent in Fayoum in
      line with the national prevalence and associated with age, gender, regularity of
      father's employment, and dietary factors.

PMID- 29201064
TI  - Use of Personal Protective Equipment among Building Construction Workers in
      Kampala, Uganda.
AB  - Background: 270 million workplace accidents occur annually. In Uganda, Kampala
      district has the highest workplace injury and fatality rates. However,
      information on personal protective equipment (PPE)-hand gloves, hardhats,
      overalls, safety boots, earplugs, safety harness with lanyard, and face shields
      utilization among building construction workers remains scarce. We assessed PPE
      utilization and determinants among building construction workers in Kampala,
      Uganda. Methods: This cross-sectional study involved 385 respondents. Data
      collected by structured questionnaire was double-entered in EpiData and analyzed
      in STATA at 5% significance level. Independent determinants of PPE use were
      established by a stepwise backward logistic regression analysis. Results: 305
      (79.2%) respondents were males, 290 (75.3%) were 18-30 years, 285 (74.0%)
      completed secondary education, and 197 (51.2%) were temporary employees. 60
      (15.6%) respondents used PPE. Female sex (adjusted odds ratio (AOR) = 6.64; 95%
      CI: 1.55-28.46; P = 0.011), temporary (AOR = 0.05; 95% CI: 0.01-0.27; P < 0.001)
      and casual (AOR = 0.01; 95% CI: 0.001-0.071; P < 0.001) employment, and previous
      knowledge of safety measures (AOR = 100.72; 95% CI: 26.00-390.16; P < 0.001) were
      associated with PPE use. Conclusion: PPE use was low in Kampala, Uganda. Building
      construction companies should implement measures of the Uganda Occupational
      Health and Safety Act.

PMID- 29201065
TI  - A medical calculator to determine testicular volumes matching ultrasound values
      from the width of the testis obtained in the scrotum with a centimeter ruler.
AB  - The determination of the testicular volume is of considerable importance to
      assess the onset, progression and disorders of puberty, abnormal testicular
      development, and a number of other conditions; and in adults, assessment of
      fertility. A number of clinical methods have been used for the measurement of
      testicular volumes in the scrotum: a centimeter ruler, sliding calipers, and
      orchidometers. All the clinical methods calculate the volumes by the ellipsoid
      equation, grossly overestimate ultrasound (US) volumes by 70 to 80% for adults,
      to 150 to 250% for prepubertal subjects, mainly because the inclusion of the
      scrotal skin and epididymis and may not be accurate of reproducible. Ultrasound
      measurements have a high degree of accuracy and reproducibility and are the
      standard for quantitation of testicular volume. Formulas, equivalent to the
      ellipsoid equations used, were developed to match ultrasound volumes, with
      corrections of the width and length of the testis obtained in the scrotum, to
      avoid the inclusion of the scrotal skin (ss) and epididymis. A calculator was
      developed, requiring only the identification of 1 the width of the testis in cm
      obtained in the scrotum with a ruler (without corrections) (i.e. 0.9, 1.5, 2.0,
      2.4 cm etc.) and 2 the stage of genital development. The calculator will subtract
      the scrotal skin for the stage of genital development, from the measurement of
      the width provided, apply the formula and identify the testicular volume of the
      subject that matches the US volume. The calculator will also provide, in a Table
      form, the values for the different stages of genital development. Benefit: The
      information provided by the calculator will solve the problem of overestimation
      by the orchidometers and the external measurements, problems with the reference
      of values to age, and Tanner stages, would permit assessment of the beginning and
      progression of puberty, of micro and macroorchidism, and other conditions
      mentioned.

PMID- 29201066
TI  - Anaphylactic shock following castor bean contact: a case report.
AB  - Background: The castor bean plant, Ricinus communis, is known to have allergenic
      and toxic properties. Castor bean allergy has been described mainly as an
      occupational inhalation allergy in laboratory workers, in persons working in oil
      processing mills or in agricultural industry. So far, only one case of
      anaphylactic reaction due to castor bean sensitization confirmed by specific IgE
      has been described in literature. Case presentation: A 30-year-old woman
      presented to the emergency room with severe angioedema followed by urticaria,
      hypotension and tachycardia. She recovered after treatment with antihistamines,
      corticosteroids, nebulized adrenaline and intravenous fluids. Food induced
      anaphylaxis was excluded by allergological investigations. After repeated
      thorough history, the patient mentioned having bitten into a castor bean just
      before the reaction. Cutaneous test (prick-to-prick) and specific IgE for castor
      bean were highly positive. Conclusions: We report the second case of a severe
      anaphylactic reaction to castor beans, confirmed by IgE testing, reported in the
      literature. It underlines the importance of a meticulous history in allergology
      and highlights the fact, that castor beans may cause potentially fatal
      anaphylaxis.

PMID- 29201067
TI  - Hereditary Vitamin D Resistant Rickets: Clinical, Laboratory, and Genetic
      Characteristics of 2 Iranian Siblings.
AB  - Purpose and Methods: Hereditary vitamin D resistant rickets (HVDRR) is a rare
      disease that presents with signs and symptoms of rickets, alopecia, and growth
      retardation during the early years of life. The disease is caused by mutations in
      the vitamin D receptor (VDR) gene, which leads to unresponsiveness of the mutant
      receptor to 1-25(OH) 2 D3. The disease is transmitted as an autosomal recessive
      disorder and is found with equal frequency in males and females. The disease is
      rarely encountered and only about 100 cases are reported so far. The current
      paper reported the clinical and laboratory characteristics of 2 Iranian siblings
      with this disorder. Results and Conclusion: They presented with rickets, growth
      retardation, muscle weakness, hypocalcemia and alopecia totalis since early
      childhood, and were followed up for 27 years. Sequencing of the DNA extracted
      from the peripheral white blood cells showed a missense G to A mutation in exon
      number 4 (g.30994 G > A) that led to the methionine substitution for the
      naturally occurring valine at position 26 in the DNA binding domain (DBD) of the
      VDR.

PMID- 29201068
TI  - Gender Identity in Patients with Congenital Adrenal Hyperplasia.
AB  - Background: Sex assignment in infancy for patients with disorder of sex
      development (DSD) is a challenging problem. Some of the patients with congenital
      adrenal hyperplasia (CAH) have DSD that may affect their gender identity.
      Objectives: The study aimed to assess gender identity in patients with CAH.
      Methods: In this study, 52 patients with CAH, including 22 prepubertal children
      and 30 adolescents and adults, were assessed using two separate gender identity
      questionnaires for children and adults based on the criteria of diagnostic and
      statistical manual of mental disorders, 5th edition. Results: In the children
      group, compatibility was seen between gender identity and rearing gender. In the
      adult group, there were three cases of mismatching between gender identity and
      sex assignment composed of two females with poor control and one male with good
      control with 21-hydroxylase deficiency (21-OHD). Three girls with 11-hydroxylase
      deficiency (11-OHD) were reared as boy. Two of them with late diagnosis at 5 and
      6 years of age had pseudoprecocious puberty. Parents and children did not accept
      to change the gender. One of them is 36 years old now, is depressed and
      unsatisfied with her gender, another girl is still child and has male sexual
      identity. One girl with 11-OHD and early diagnosis at birth with Prader 5
      virilization but with good hormonal control was changed to female gender at 12
      years of age when female sexual characteristics appeared; she is 34-years-old
      now, married, and with two children, and she is satisfied with her gender.
      Conclusions: In patients with CAH, gender identity disorder is a rare finding.
      Hormonal control, social, familial, and religious beliefs have impacts on gender
      identity of these patients.

PMID- 29201069
TI  - Knowledge, Attitude and Practices (KAP) Regarding Chronic Complications of
      Diabetes among Patients with Type 2 Diabetes in Dhaka.
AB  - Background: To reduce morbidity and mortality, awareness regarding diabetes and
      its complications is necessary. This study aimed at assessing the level of
      knowledge, attitude, and practices (KAP) regarding complications of diabetes
      mellitus among patients with type 2 diabetes in Dhaka, Bangladesh. Methods: A
      cross-sectional study was carried out recruiting patients with diabetes from the
      outpatient department of BIRDEM hospital in Dhaka. Overall, 425 patients with
      diabetes were enrolled in this study. A pretested questionnaire was filled by the
      interviewer with face to face interview. Levels of KAP were determined by
      calculating the scores. Multivarable linear regression was used to determine
      significant predictors for knowledge, attitude, and practices. Results: On
      average, the level of knowledge, attitude, and practices were 9.2 (out of 14),
      7.9 (out of 13), and 16.9 (out of 27), respectively. Age and gender were
      significant predictors of knowledge and attitude. Females had better level of
      knowledge and attitude compared to males (betas = 0.55 and 1.24, respectively).
      Patients with graduate degrees and above compared to illiterates reported
      significantly greater knowledge and practice (betas = 1.27 and 1.44,
      respectively), after adjustments for covariates. Educational program was the most
      important significant predictor of KAP. Higher duration of diabetes (beta = 0.07)
      and positive marital status (beta = 1.21) had influenced better practice.
      Conclusions: Lack of knowledge, poor attitude, and inadequate practice were found
      in this surveyed communinty. Level of education and educational program on
      diabetes were the most significant contributing factors. The current study
      suggests the need of structured educational programs on diabetes and its
      complications on a regular basis to assist patients in living a productive life.

PMID- 29201070
TI  - Rapid Weight Loss vs. Slow Weight Loss: Which is More Effective on Body
      Composition and Metabolic Risk Factors?
AB  - Background: Achieving weight loss (WL) in a short time regardless of its
      consequences has always been the focus of many obese and overweight people. In
      this study, anthropometric and metabolic effects of two diets for rapid and slow
      WL and their consequences were examined. Methods: Forty-two obese and overweight
      individuals were randomly divided to 2 groups; rapid WL (weight loss of at least
      5% in 5 weeks) and slow WL (weight loss of at least 5% in 15 weeks). To compare
      the effects of the rate of WL in 2 groups, the same amount of was achieved with
      different durations. Anthropometric indices, lipid, and glycemic profiles, and
      systolic and diastolic blood pressures were evaluated before and after the
      intervention. Results: Both protocols of rapid WL and slow WL caused reduction in
      waist circumference, hip circumference, total body water, body fat mass, lean
      body mass, and resting metabolic rate (RMR). Further reduction in waist
      circumference, hip circumference, fat mass, and percentage of body fat was
      observed in slow WL and decreased total body water, lean body mass, fat free
      mass, and RMR was observed in rapid WL. Improvement in lipid and glycemic
      profiles was observed in both groups. Reduction of low-density lipoprotein and
      fasting blood sugar, improvement of insulin resistance, and sensitivity were more
      significant in rapid WL in comparison to slow WL. Conclusions: Weight Loss
      regardless of its severity could improve anthropometric indicators, although body
      composition is more favorable following a slow WL. Both diets improved lipid and
      glycemic profiles. In this context, rapid WL was more effective.
      (IRCT2016010424699N2).

PMID- 29201071
TI  - Hemostasis in Overt and Subclinical Hyperthyroidism.
AB  - Context: There are contradictory results on the effect of hyperthyroidism on
      hemostasis. Inadequate population-based studies limited their clinical
      implications, mainly on the risk of venous thromboembolism (VTE). The present
      review focuses on hemostatic changes in overt and subclinical hyperthyroidism.
      Methods: A systematic literature search was conducted employing MEDLINE database.
      The following words were used for the search: Hyperthyroidism; thyrotoxicosis;
      Graves disease; goiter, nodular; hemostasis; blood coagulation factors; blood
      coagulation disorders; venous thromboembolism; bleeding; fibrinolysis. The
      articles that were related to hyperthyroidism and hemostasis are used in this
      manuscript. Results: Hyperthyroidism, either overt or subclinical, renders a
      hypercoagulable state, although there are several studies with contradictory
      findings in the literature. Hypercoagulability may be caused by an increase in
      the level of various coagulation factors such as factor (F) VIII, FX, FIX, von
      Willebrand F (vWF), and fibrinogen, while hypofibrinolysis by changes in
      coagulation parameters such as a decrease in plasmin and plasmin activator or an
      increase in alpha2-antiplasmin, plasminogen activator inhibitor-1 and thrombin
      activatable fibrinolysis inhibitor. Conclusions: Although many reports are in
      favor of a hypercoagulable state in overt hyperthyroidism but this finding at the
      biochemical level and its clinical implication, on the occurrence of VTE, has yet
      to be confirmed.

PMID- 29201073
TI  - Knowledge of Thyroid Disorders during Pregnancy among General Practitioners in
      Iran.
AB  - Background and Objectives: Thyroid disorders during pregnancy are important
      health problems worldwide. The aim of this study was to assess the knowledge of
      general practitioners (GPs) about thyroid disorders during pregnancy. Methods: In
      this cross sectional study, 120 GPs were randomly selected among participants of
      a continuous medical education (CME) program, entitled "practical endocrinology".
      To assess the knowledge and educational requirements of GPs regarding thyroid
      disorders during pregnancy, a validated and localized multiple-choice
      questionnaire was used. Results: A total of 100 GPs completed the questionnaire.
      The mean age of the participants was 37.0 years, and 41.4% were men. The mean
      knowledge score of GPs was 39.9%. On average, the rate of correct response to
      questions concerning the definition, pathophysiology, diagnosis, complications,
      and treatment of thyroid disorders was 39.0%, 39.3%, 48.8%, 34.3%, and 44.6%,
      respectively. There was a significant difference in knowledge among GPs, who had
      and had not passed the training course on thyroid disorders. In addition, GPs who
      had passed continuous medical education programs obtained higher knowledge scores
      regarding diagnosis and treatment (P < 0.05). Conclusions: GPs attending pregnant
      women in Iran lack sufficient information on the pathophysiology, diagnosis, and
      management of thyroid disorders during pregnancy. Considering the key role of GPs
      in the public healthcare system, design of high-quality educational programs and
      development of specific educational packages about thyroid disorders and
      pregnancy are necessary.

PMID- 29201072
TI  - The Role of Kisspeptin in Female Reproduction.
AB  - Context: Kisspeptin (KISS1), a recently discovered neuropeptide that acts
      upstream of gonadotropin-releasing hormone (GnRH) neurons, is critical for
      maturation and function of the reproductive axis. This review aimed at providing
      comprehensive and up-to-date information on Kisspeptin and its role in female
      reproduction. Evidence Acquisition: A literature review was performed using
      PubMed for all English language articles published between 1999 and 2016.
      Results: The kisspeptin system (KISS1/G protein-coupled receptor-54,GPR54) has
      recently been addressed as an essential gatekeeper of puberty onset and
      gonadotropin secretion. Compelling evidence has documented that hypothalamic
      Kisspeptin mediates steroid feedback and metabolic cues at different
      developmental stages throughout lifespan. Furthermore, in pre/postnatally
      androgenized animal models, which exhibit many of the characteristics of
      Polycystic Ovarian Syndrome (PCOS), the hypothalamic expression of KISS1 and GnRH
      is abnormal, which might lead to multiple tissue abnormalities observed in this
      disorder. Conclusions: Kisspeptin, a principal activator of GnRH neurons and the
      target of endocrine and metabolic cues, is a prerequisite for the onset of
      puberty and maintenance of normal reproductive function, as abnormal KISS1/GPR54
      system has been reported in both animal models and patients with certain forms of
      infertility, e.g. Idiopathic Hypogonadotropic hypogonadism (IHH) and PCOS. The
      information suggests that kisspeptin or its receptor represents a potential
      therapeutic target in the treatment of patients with fertility disorders.

PMID- 29201075
TI  - Development and Evaluation of Patient Information Leaflet for Diabetic Foot Ulcer
      Patients.
AB  - Background: Patient education (PE) is as important as medical and surgical
      interventions in the management of diabetic foot ulcer (DFU). Patient information
      leaflets (PILs) are globally accepted patient counseling aids. Objectives: This
      study aimed at developing PILs for DFU patients and investigating its validation.
      Methods: The PILs were prepared based on different model leaflets available from
      various online resources, including "Patient UK". The PILs readability was
      evaluated by Flesch/ Flesch-Kincaid readability (FRE/FK-GL) method before user
      testing (n = 34 DFU patients) by quasi-experimental methods in patients with DFU.
      Additionally, user-opinion on legibility and content of the PIL was also
      determined. Baker Able Leaflet Design (BALD) method was employed to assess the
      layout and design characteristics of the PIL. Results: The best FRE score
      achieved was 73.9 and the FK-GL score was 6.1. The mean BALD assessment score for
      English and Kannada versions of PIL were 27 and 26, respectively. The ICC of the
      test-retest reliability of user-testing and user-opinion questionnaires in both
      English and Kannada ranged from 0.91 to 0.96. The overall user-testing knowledge
      based mean score significantly improved from 43.4 to 69.7 (P < 0.05). Overall,
      82.4% of patients reported overall user-opinion on legibility and content of the
      PIL as good. Conclusions: The developed PILs met the criteria of fairly easy
      readability and good layout design. The user-opinion of the majority of patients
      reported the PIL content, legibility, and design as good. The Pictogram-based
      PILs (P-PILs) was found to be an effective PE tool in DFU patients.

PMID- 29201074
TI  - Worldwide Recall Rate in Newborn Screening Programs for Congenital
      Hypothyroidism.
AB  - Context: Neonatal mass screening program for congenital hypothyroidism provides
      the best tool for prevention of its devastating effects on mental development.
      Despite the overall success of the screening programs in detecting congenital
      hypothyroidism and eliminating its sequelae and new developments made in the
      program design, high recall rate and false positive results impose a great
      challenge worldwide. Lower recall rate and false positive results may properly
      organize project expenses by reducing the unnecessary repeated laboratory tests,
      increase physicians and parents' assurance and cooperation, as well as reduce the
      psychological effects in families. Evidence Acquisition: In this review, we
      assessed the recall rate in different programs and its risk factors worldwide.
      Methods: Publications reporting the results of the CH screening program from 1997
      to 2016 focusing on the recall rate have been searched. Results: Recall rates
      vary from 0.01% to 13.3% in different programs; this wide range may be due to
      different protocols of screening (use of T4 or TSH or both), different laboratory
      techniques, site of sample collection, recall cutoff, iodine status, human error,
      and even CH incidence as affected by social, cultural, and regional factors of
      the population. Conclusions: It is suggested to implement suitable interventions
      to reduce the contributing factors by improving the quality of laboratory tests,
      selecting conservative cut off points, control iodine deficiency, use of iodine
      free antiseptic during delivery, and use of more specific markers or molecular
      tests. Applying an age dependent criteria for thyrotropin levels can be helpful
      in regions with a varied time of discharge after delivery or for preterm babies.

PMID- 29201076
TI  - Formulation Development and Evaluation of the Therapeutic Efficacy of
      Brinzolamide Containing Nanoemulsions.
AB  - Brinzolamide (BZ) is an intraocular pressure reducing agent with low
      bioavailability. The purpose of the present study was to overcome this issue by
      development of BZ containing nanoemulsions (NEs) as an ocular drug delivery
      system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the
      spontaneous emulsification method. Based on initial release studies, twelve
      formulations with the slowest release characteristics were subjected to further
      physicochemical investigations such as particle size, polydispersity index, pH,
      refractive index, osmolality and viscosity. The therapeutic efficacy of these
      formulations was assessed by measuring the intraocular pressure after
      instillation of the prepared NEs in normotensive albino rabbit eyes.
      Nanoemulsions with suitable physicochemical properties exhibited high formulation
      stability under different conditions. more over biological evaluations indicated
      that using lower drug concentrations in NE formulations (0.4%) had a similar or
      even better pharmacodynamic effect compared to the commercial suspension with a
      higher drug concentration (1%). Our findings suggest that NEs could be
      effectively used as carriers for enhancing the bioavailability of topically
      applied ophthalmic drugs.

PMID- 29201077
TI  - A New Approach to Antivenom Preparation Using Chitosan Nanoparticles Containing
      EchisCarinatus Venom as A Novel Antigen Delivery System.
AB  - In recent years, use of biodegradable polymers based nanoparticles has received
      high interest in the development of vaccines delivery vehicles. The aim of study
      was to prepare chitosan nanoparticles (CS NPs) for loading Echis carinatus (EC)
      venom and evaluate their potential as an adjuvant and antigen delivery system on
      a pilot scale. CS NPs were prepared using ionic gelation method, and their
      characteristics were optimized. Venom-loaded CS NPs prepared under optimum
      conditions and traditional venom-loaded adjuvants were used to hyperimmunization
      of horse. Under optimum conditions, particle size, polydispersity index (PDI),
      and zeta potential of CS NPs were 127.9 +/- 15 nm, 0.29, and +19.8 +/- 1.92 mV,
      while those of venom-loaded CS NPs were 182.4 +/- 20 nm, 0.35, +26.8 +/- 1.98 mv,
      respectively. All CS NPs had integrated surface and good morphology. Optimum
      loading concentration of EC venom was 500 ug/mL. The loading capacity (LC) and
      loading efficiency (LE) were 87% and 94%, respectively, and release profile of
      venom-loaded CS NPs showed suitable correlation with Higuchi kinetics. Stability
      test showed good stability of the venom encapsulated in CS NPs. Furthermore,
      antivenom plasma obtained using the new antigen delivery system had significantly
      higher potency (P < 0.05) for neutralizing the venom than that obtained using
      conventional system. These results suggested that venom-loaded CS NPs could be a
      suitable alternative to conventional adjuvant for development antivenom.

PMID- 29201078
TI  - Anticancer Activity of Curcumin-Loaded PLGA Nanoparticles on PC3 Prostate Cancer
      Cells.
AB  - Curcumin (Cur) has been found to be very efficacious against many different types
      of cancer cells. However, the major disadvantage associated with the use of Cur
      is its low systemic bioavailability. Our present work investigated the toxic
      effect of encapsulation of Cur in PLGA (poly lactic-coglycolic acid) nanospheres
      (NCur) on PC3 human cancer prostate cell. In the present study, we have
      investigated the effects of NCur on growth, autophagia, and apoptosis in PC3
      cells, respectively, by MTT assay, fluorescence microscopy, and Flow cytometry.
      MTT assays revealed that the NCur at the concentration of 25 ug/mL for 48 h were
      able to exert a more pronounced effect on the PC3 cells as compared to free Cur.
      Apoptotic index was significantly increased in NCur-treated cells compared to
      free Cur. The percentage of autophagic cells (LC3-II positive cells) was also
      significantly increased in NCur treatment in comparison to free Cur. These data
      indicate that the NCur has considerable cytotoxic activity more than Cur on PC3
      cell lines, which is mediated by induction of both apoptotic and autophagic
      processes. Thus, NCur has high potential as an adjuvant therapy for clinical
      application in prostate cancer.

PMID- 29201079
TI  - Docking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on
      Nitrones as Reactivators of Inhibited Acetylcholinesterase.
AB  - Acetylcholinesterase has important role in synaptic cleft. It breaks down the
      acetylcholineat cholinergic synapsesand terminates the cholinergic effects. Some
      chemical agents like organophosphorus compounds (OPCs) including nerve agents and
      pesticides react with acetylcholinesteraseirreversibly. They inhibit normal
      biological enzyme action and result in accumulation of acetylcholineand show
      toxic effects andcholinergic symptoms. The process of Acetylcholinesterase (AChE)
      inhibition can be reversed by a nucleophilic agent to dephosphorylate and
      reactivate the enzyme. In this study, design and docking studies of 15 novel
      nitrone based onoximes as reactivators were performed by using AutoDock program.
      Then, more effective reactivatorsoximes in terms of binding energy and
      orientation within the active site were synthesized and evaluated in-vitro on
      human AChE (hAChE) inhibited by paraoxon and compared to standard hAChE
      reactivators (2-PAM and obidoxime). Our results used to design new derivatives of
      Oxim with better efficacy than 2-PAM and obidoxime. Syntheses of some selected
      bis-pyridiniumoximes based on the nitrones are underway.

PMID- 29201080
TI  - Anticonvulsant Effects of New 1, 4-DihydropyridineDerivatives Containing
      Imidazolyl Moiety Against Seizures Induced by Pentylenetetrazole and Maximal
      Electroshock in Mice.
AB  - Epilepsy is a chronic disorder of the brain affecting around 50 million people in
      the world. Up to 30% of epileptic patients do not respond to available drugs and
      medical therapies. In this paper, anticonvulsant screening of 10 synthesized new
      derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed.
      Anticonvulsant activity was evaluated by intravenous and intraperitoneal
      pentylenetetrazole and maximal electroshock induced seizures tests. Nifedipine
      was used as reference drug. Our pharmacological results revealing the compounds
      2, 4, 5, and 6 can be effective in both absence and grandmal seizures in human.
      These pharmacological studies have displayed that these new dihydropyridine
      derivatives are capable to inhibiting seizures induced by pentylenetetrazole and
      maximal electroshock in mice efficiently.

PMID- 29201081
TI  - Synthesis and Leishmanicidal Activity of 1-[5-(5-Nitrofuran-2-yl)-1, 3, 4
      Thiadiazole-2-yl]-4-BenzoylePiperazines.
AB  - A series of (5-nitrofuran-2-yl)-1, 3, 4-thiadiazole-2-yl derivatives 6a-6e have
      been synthesized and screened for in-vitro anti-leishmanial activity against the
      promastigote form of L. major. The structure of Schiff bases were confirmed by 1H
      NMR, IR. Screening results indicate that all of the designed and synthesized
      final compounds (6a-6e) significantly reduced the viability of promastigotes of
      L. major in comparison toglucantime (IC50 3* 103 MUg/mL). Meta and Para
      substitutions in benzene ring containing compounds were more potent than other
      derivative and the most potent compounds were 6d, 6e with IC50 value 94 um and
      77.6 um, respectively. The experimental data proposes that (5-nitrofuran-2-yl)-1,
      3, 4-thiadiazole-2-yl derivatives may be further investigated as a candidate drug
      for treatment of cutaneous leishmaniasis.

PMID- 29201082
TI  - Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B
      Inhibitors.
AB  - Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma
      and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are
      known to reduce the dose limiting adverse effect associated with non-selective
      PDE4B inhibitors. This makes the development of PDE4B subtype selective
      inhibitors a desirable research goal. To achieve this goal, ligand based
      pharmacophore modeling approach is employed. Separate pharmacophore hypotheses
      for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106
      PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2
      arylpyrimidines, and triazines skeleton. Suitable training and test sets were
      created using the molecules as per the guidelines available for HypoGen program.
      Training set was used for hypothesis development while test set was used for
      validation purpose. Fisher validation was also used to test the significance of
      the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and
      PDE4D inhibitors were used in sequential virtual screening of zinc database of
      drug like molecules to identify selective PDE4B inhibitors. The hits were
      screened for their estimated activity and fit value. The top hit was subjected to
      docking into the active sites of PDE4B and PDE4D to confirm its selectivity for
      PDE4B. The hits are proposed to be evaluated further using in-vitro assays.

PMID- 29201083
TI  - Evaluation of Novel alpha-(Acyloxy)-alpha-(Quinolin-4-yl) Acetamides as
      Antiplasmodial Agents.
AB  - Because of expanding resistance to efficient and affordable antimalarial drugs
      like chloroquine, the search is continuing for more effective drugs against this
      disease. In-vitro antiplasmodial activity and cytotoxicity of alpha-(acyloxy)
      alpha-(quinolin-4-yl) acetamides on Plasmodiumfalciparum and structure-activity
      relationships of this new class of Passerini adducts is described. The in-vitro
      antiplasmodial activity of compounds was tested against chloroquine sensitive 3D7
      strain. Toxicity of active compounds was investigated on HepG2 cell line.
      Compounds 1, 20 and 22 showed significant antiplasmodial activity with IC50 value
      of 1.511, 1.373 and 1.325 uM, respectively. The active compounds did not show
      noticeable toxicity when tested against HepG2 cell line. The present results
      bring essential elements which will be used for the synthesis of more active
      derivatives of alpha-(acyloxy)-alpha-(quinolin-4-yl) acetamides.

PMID- 29201084
TI  - Design and Synthesis of Some Novel Fluorobenzimidazoles Substituted with
      Structural Motifs Present in Physiologically Active Natural Products for
      Antitubercular Activity.
AB  - Keeping in view the drawbacks associated with research on anti-TB drugs based on
      plant extracts and the non-availability of fluorinated natural products with
      antitubercular activity has prompted us to make an effort towards the synthesis
      and characterization of a novel series of fifteen substituted
      fluorobenzimidazoles. The newly synthesized compounds were characterized by I.R,
      1H-NMR, 13C-NMR, Mass, and elemental analysis. The synthesized compounds 4(a-f)
      and 5(b-j) have been evaluated for their in-vitro antimycobacterial activity
      against H37Rv strain (ATCC 27294) by MABA method. Incorporation of
      methylenedioxyphenyl moiety at 2- and 6-position of the benzimidazole ring
      furnished compounds 4d and 5i with antitubercular activity comparable or more
      potent than the naturally occurring compounds with reported antitubercular
      activity. Among the fifteen tested compounds, 4d and 5i emerged as promising hits
      characterized by MIC lower than that determined for sesamin against the
      pathogenic H37Rv strain. Antitubercular activity results indicate that these
      compounds may be suitable for further lead optimization. The cytotoxic effect of
      these active compounds on THP-1 cell line was assessed by MTT assay and the
      results suggest that these two molecules are potential candidates for further
      development as antitubercular agents.

PMID- 29201085
TI  - Synthesis and Evaluation of the Antimicrobial Activity of Spiro-4H-pyran
      Derivatives on Some Gram Positive and Gram Negative Bacteria.
AB  - Infections are one of the most important causes of death, disability and
      inappropriate conditions for millions of people around the world. Therefore, the
      development in prognosis, prevention and treatment of infectious diseases made a
      considerable progress in designing and synthesis of new antimicrobial drugs.
      Nowadays, due to the increase in microbial resistance, discovery of new compounds
      with broad spectrum effects is granted. 4H-pyran derivatives and spiro compounds
      are the most important fragments in some effective drugs with antimicrobial
      activity. Therefore, in this study, 6 compounds with spiro-4H-pyran core were
      synthesized and evaluated for their antimicrobial activity against four different
      bacterial species using microbroth dilution and disk diffusion methods. Minimum
      inhibitory concentration (MIC) has been measured for each compound and also for
      the standard antibiotic, gentamicin, and they were all compared together.
      According to our result, one of the spiropyran derivative (5d) containing both
      the indole and the cytosine ring, has been shown good antibacterial effects
      against standard and clinical isolates of Staphylococcus aureus and Streptococcus
      pyogenes.

PMID- 29201086
TI  - Esters of Quinoxaline 1'4-Di-N-oxide with Cytotoxic Activity on Tumor Cell Lines
      Based on NCI-60 Panel.
AB  - Quinoxalines display diverse and interesting pharmacological activities as
      antibacterial, antiviral, antiparasitic and anticancer agents. Particularly,
      their 1'4-di-N-oxide derivatives have proved to be cytotoxic agents that are
      active under hypoxic conditions as that of solid tumours. A new series of
      quinoxaline 1'4-di-N-oxide substitutes at 7-position with esters group were
      synthetized and characterized by infrared (IR), proton nuclear magnetic resonance
      (1H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1
      E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using
      the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were
      the most active compounds against the cell lines tested. Substitutions at 7
      position with esters group not necessarily affect the biological activity, but
      the nature of the esters group could exert an influence on the selectivity.
      Additionally, substitutions at 2-position influenced the cytotoxic activity of
      the compounds.

PMID- 29201088
TI  - Evaluation of a 99mTc-tricine Vascular Disrupting Agent as an In-vivo Imaging in
      4T1 Mouse Breast Tumor Model.
AB  - Colchicine as a vascular disrupting agent creates microtubule destabilization
      which induces vessel blockage and consequently cell death. Accordingly,
      colchicines and its analogues radiolabeled with 99mTc may have potential for
      visualization of tumor. In this work, deacetylcolchicine a colchicine analogue
      was labeled with 99mTc via tricine as a coligand and characterized for its tumor
      targeting properties. The in-vitro radiochemical stability and the
      biodistribution were studied in 4T1 breast tumor model bearing mice. Labeling
      yield of more than 90% was obtained corresponding to a specific activity of 46
      MBq/umol. In-vivo biodistribution studies demonstrated that radiocomplex had high
      tumor to muscle and tumor to blood ratios at early time points. Planer gamma
      imaging of tumor bearing mice showed that this radioconjugate was able to clearly
      visualize tumors. According to high tumor uptake, presented radiocomplex may have
      a potential for targeted imaging studies.

PMID- 29201087
TI  - QSAR Study of 17beta-HSD3 Inhibitors by Genetic Algorithm-Support Vector Machine
      as a Target Receptor for the Treatment of Prostate Cancer.
AB  - The 17beta-HSD3 enzyme plays a key role in treatment of prostate cancer and small
      inhibitors can be used to efficiently target it. In the present study, the
      multiple linear regression (MLR), and support vector machine (SVM) methods were
      used to interpret the chemical structural functionality against the inhibition
      activity of some 17beta-HSD3inhibitors. Chemical structural information were
      described through various types of molecular descriptors and genetic algorithm
      (GA) was applied to decrease the complexity of inhibition pathway to a few
      relevant molecular descriptors. Non-linear method (GA-SVM) showed to be better
      than the linear (GA-MLR) method in terms of the internal and the external
      prediction accuracy. The SVM model, with high statistical significance (R2train =
      0.938; R2test = 0.870), was found to be useful for estimating the inhibition
      activity of 17beta-HSD3 inhibitors. The models were validated rigorously through
      leave-one-out cross-validation and several compounds as external test set.
      Furthermore, the external predictive power of the proposed model was examined by
      considering modified R2 and concordance correlation coefficient values, Golbraikh
      and Tropsha acceptable model criteria's, and an extra evaluation set from an
      external data set. Applicability domain of the linear model was carefully defined
      using Williams plot. Moreover, Euclidean based applicability domain was applied
      to define the chemical structural diversity of the evaluation set and training
      set.

PMID- 29201089
TI  - Thermo-, Radio- and Photostability of Perindopril Tert-butyloamine in The Solid
      State. Comparison to Other Angiotensin Converting Enzyme Inhibitors.
AB  - The main aim of this study was determination of thermo- radio- and photostability
      of perindopril tert-butyloamine (PER) therefore the efficiency and safety of the
      therapy could be maintained. A chromatographic method (RP-HPLC) had been
      validated before use to determine PER loss. The evaluation of stability
      properties of PER in solid state under the influence of isothermal condition,
      relative humidity - RH = 0% and 76.4%, exposure to 6 mln lux h and ionizing
      radiation generated by beam of electrons of 25-400 kGy was investigated. Studies
      pointed out that presence of moisture changes a kinetic model of PER degradation;
      lack of moisture in the air generates a first-order kinetic model of the
      reaction, increase humidity generates the autocatalytic model. PER proved to be
      resistant for ionizing radiation. It is possible to use radiation sterilization
      and decontamination (dose 25 kGy) with no significant loss of content.
      Investigation of PER photostability proved, that after exposure to 6 mln lux h
      physicochemical parameters are acceptable. Among all the ACE-I, PER has one of
      the shortest t0,5. PER should be stored in closed containers, protected from high
      temperature and moisture. PER is referred to be photostable and resistant for
      radiodegradation.

PMID- 29201090
TI  - Voltammetric Determination of Penicillamine Using a Carbon Paste Electrode
      Modified with Multiwall Carbon Nanotubes In the Presence of Methyldopa as a
      Mediator.
AB  - A multiwall carbon nanotubes-modified carbon paste electrode (MWCNTs/MCPE) was
      fabricated and used to study the electrooxidation of penicillamine (PA) by
      electrochemical methods in the presence of methyldopa (MDOP) as a homogeneous
      mediator. The electrochemical oxidation of PA on the new sensor has been
      carefully studied. The kinetic parameters such as electron transfer coefficient,
      alpha, and catalytic reaction rate constant, K/h, were also determined using
      electrochemical approaches. The electrocatalytic oxidation peak current of PA
      showed a linear dependent on the PA concentrations and linear calibration curves
      were obtained in the ranges of 0.2-250.0 uM of PA concentration with square wave
      voltammetry (SWV) method. The detection limit (3sigma) was determined as 0.1 uM.
      This sensor was also examined as a fast, selective, simple and precise new sensor
      for voltammetric determination of PA in real samples such as drug and urine.

PMID- 29201091
TI  - Determination of Aluminum in Dialysis Concentrates by Atomic Absorption
      Spectrometry after Coprecipitation with Lanthanum Phosphate.
AB  - This method was developed for the determination of trace amounts of aluminum(III)
      in dialysis concentrates using atomic absorption spectrometry after
      coprecipitation with lanthanum phosphate. The analytical parameters that
      influenced the quantitative coprecipitation of analyte including amount of
      lanthanum, amount of phosfate, pH and duration time were optimized. The %
      recoveries of the analyte ion were in the range of 95-105 % with limit of
      detection (3s) of 0.5 ug l-1. Preconcentration factor was found as 1000 and
      Relative Standard Deviation (RSD) % value obtained from model solutions was 2.5%
      for 0.02 mg L-1. The accuracy of the method was evaluated with standard reference
      material (CWW-TMD Waste Water). The method was also applied to most concentrated
      acidic and basic dialysis concentrates with satisfactory results.

PMID- 29201092
TI  - Development of a New Method Based on Chiral Ligand-Exchange Chromatography for
      the Enantioseparation of Propranolol.
AB  - A new chromatographic procedure was proposed for the separation of propranolol
      (PRN) enantiomers based upon enantioselective chiral ligand-exchange
      chromatography. The separation was carried out on a short C8 column leading to
      considerably short separation time. L-alanine and Cu2+ were applied as chiral
      selector and central bivalent complexing ion, respectively. It was found that the
      kind of copper salt could influence the enantioseparation efficiency. The
      separation on the C8 stationary phase was more efficient than that on the C18
      column. It was shown that the pH of mobile phase, organic modifier content of
      mobile phase, mole ratio of chiral ligand to bivalent ion and Cu (L-alanine) 2
      concentration in the mobile phase were important in enantioseparation efficiency.
      Water/methanol (70:30) mixture containing L-alanine-Cu2+ (7:1) was found to be
      the best mobile phase condition for PRN enantioseparation. All effective
      parameters were optimized in order to improve the separation efficiency. The
      optimized HPLC method was utilized for analysis of propranolol enantiomers in
      spiked human blood plasma samples.

PMID- 29201093
TI  - Simultaneous Determination of Residue from 58 Pesticides in the Wheat Flour
      Consumed in Tehran, Iran by GC/MS.
AB  - Food safety has a direct impact on human health and as such is a growing concern
      worldwide. Presence of harmful pesticide residue in food is a serious cause for
      concern among consumers so it is important to monitor levels of pesticides in
      foods. The aim of this study was simultaneous determination of concentrations of
      58 pesticides in 40 wheat flour samples collected from Tehran market in January,
      2014. The city under study (Tehran) was divided into five districts and samples
      were collected independently from each district and sourced from different
      bakeries (n=40). A gas chromatography-mass spectrometry single quadrupole
      selected ion monitoring "GC/MS-SQ-SIM" method was used to quantify residue of 58
      pesticides in the wheat flour samples. Four of the 40 samples showed
      contamination with Malathion (2 samples: 50.96 +/- 11.38 and 62.088 +/- 11.38
      ppb) and 2, 4-DDE (2 samples: 19.88+/-15.24 and 13.7 +/- 15.24 ppb). that had
      levels below MRLs of these pesticides in Iran. Averages of recovery of pesticides
      at 6 concentration levels were in the range of 81.61-118.41%. The method was
      proven as repeatable with RSDr in the range of 6.5-29.45% for all concentration
      levels. The limit of quantification for 37 of the tested pesticides was
      calculated as 15 ppb and for the other 21 tested pesticides, the concentration
      was 25 ppb. In summary, results of these tests suggested that the wheat flour
      consumed in Tehran, was within safety limits in terms of levels of pesticide
      residues.

PMID- 29201094
TI  - Comparison of Kinetic Study and Protective Effects of Biological Dipeptide and
      Two Porphyrin Derivatives on Metal Cytotoxicity Toward Human Lymphocytes.
AB  - In this research, dipeptide (his-beta-alanine) and porphyrin derivatives were
      choosen for comparing chelating ability of toxic metals such as Al3+, Cu2+, Hg2+
      and Pb2+in-vitro. The reason for choosing these two compounds is that both of
      them are naturally present in biological systems and comparison of chelating
      ability of these two compounds has not yet been done. Synthesis and comparison of
      kinetic study of dipeptide (his-beta-alanine), meso-tetrakis(4
      trimethylanilinium) porphyrin (TAPP) and Tetrakis(4-sulfonatophenyl)porphyrin
      (TPPS4) were carried out by our team. In addition, cytotoxicity assays of metals
      and chelators were also performed using methylthiazoletetrazolium (MTT) test.
      Furthermore we investigated the protective effect of chelators against
      cytotoxicity, induced by differenrt toxic metals such as Al3+, Cu2+, Hg2+ and
      Pb2+ on human lymphocytes. EC50 values on human lymphocytes obtained after 12 h.
      incubation for Al3+, Cu2+ and Hg2+ were 30, 51, 3 uM respectively and for Pb2+ no
      cytotoxicity was observed on human lymphocyte up to 1000 uM concentration. EC50
      obtained for chelators dipeptide, TPPS4 and TAPP were 948, 472 and 175 uM
      respectively. Pretreatment of human lymphocyte with subtoxic concentations of
      chelators reduced toxicity of the metals against human blood lymphocytes.

PMID- 29201095
TI  - Toxicity Assessment of Asteraceae Centaurea Repens L Extract in Mice.
AB  - The species Asteraceae Centaurea repens (Asteraceae), known as Acroptilon repens,
      and Talkhe in persian is used in folk medicine as an emetic, anti-epileptic, and
      anti-malaria herb in many parts of the world but its toxic effects have not
      determined yet. This study aimed to evaluate the acute and subchronic toxicity of
      this extract to find its possible adverse health effects through clinical,
      hematological, biochemical, and histopathological endpoints in both gender of
      mice. Aerial parts of the plant were air-dried and the terpene extract of aerial
      parts of plant was provided by percolation using methanol, petroleum ether, and
      diethyl ether. All clinical, biochemical and histopathological changes were
      assessed in appropriate endpoints and compared with control group. Although no
      mortality was seen in acute study by administrating doses up to 2000 mg/kg,
      repeated dose study on 1000 mg/kg doses in 28 days in both genders showed liver
      necrosis and rise of liver enzymes (p-value < 0.05). Histopathological studies
      didn't show any other organ toxicity in dosed up to 1000 mg/kg. At the same time
      this study showed for the first the antihyperlipidemic properties of the aerial
      extract of Acroptilin in mice model. The pharmacological and histopathological
      results of the present study proved that the total parts of Acroptilon repens
      could be studied for supporting the traditional assertion in folk medicine to
      heal hyperlipidemia, diabetes, and cancer in lower doses although we performed
      the present study and concluded liver toxicity by subchronic use of Acropitolon
      repens extract.

PMID- 29201096
TI  - Antihyperglycemic Effect of Rosa Damascena is Mediated by PPAR.gamma Gene
      Expression in Animal Model of Insulin Resistance.
AB  - Insulin resistance is a condition in which insulin signaling and action are
      impaired in insulin sensitive tissues and result in hyperglycemia,
      hyperlipidemia, and type 2 diabetes mellitus. Our previous studies have shown
      that Rosa damascena has antihyperglycemic effects on diabetic and normal rats.
      Therefore, we conducted a study to evaluate the effect of this medicinal plant on
      insulin sensitivity in rats. This study was performed on high fructose diet
      insulin resistant rats and pioglitazone, an insulin sensitizing drug, was used as
      a positive control. Insulin resistance was developed in animals by high fructose
      diet within six weeks. Then, Rosa damascena extract and pioglitazone were
      administered by gavage for two weeks and results were compared with two control
      groups. After treatment period, serum glucose, insulin, adiponectin,
      triglyceride, and cholesterol were assayed in fasting state. Plasma free fatty
      acid profile was analyzed by GC. Liver PPAR.gamma and muscle GLUT.4 gene
      expressions were assessed by real time PCR and western blotting. Animals were
      treated with rosa damascena extract showed levels of insulin (42 +/- 2.7 pmol/L).
      adiponectin (5.6+/-0.17 MUg/mL). glucose (129+/-4.7 mg/dL). and triglyceride (75
      +/- 9 mg/dl) which were significantly improved as compared with control group
      insulin (137 +/- 34 pmol/L), adiponectin (3.9+/-0.15 MUg/mL). glucose (187+/-15
      mg/dL). and triglycerides (217+/-18 mg/dL). PPARgamma protein level was also
      significantly increased in Rosa damascene treated group. Our results demonstrated
      that rosa damascena extract has useful effects on insulin resistant animals and
      by increasing insulin sensitivity can be considered as a potential agent in
      control of diabetes.

PMID- 29201097
TI  - The Evaluation and Comparing of Cytotoxic Effects of Ferula gummosa Gum,
      Scutellaria lindbergii, Kelussia odoratissima and Artemisia kopetdaghensis
      Extracts on ACHN Cell Line.
AB  - Renal cell carcinoma (RCC) is one of most fatal cancers. In most patients it is
      resistant to chemotherapy. Ferula gummosa gum, Scutellaria lindbergii, Kelussia
      odoratissima, and Artemisia kopetdaghensis are herbs about which there are some
      cytotoxic activity reports. In this study, cytotoxic and apoptotic activity of
      these four extracts on RCC cell line (ACHN) were evaluated and compared (ACHN)
      cells were treated with different concentrations of herbal extracts (15-500
      MUg/mL). Cell proliferation was determined after 24, 48, and 72 h. by MTT assay.
      Apoptotic cells were determined using PI staining of DNA fragmentation by flow
      cytometry. Cell viability decreased with all herbal extracts in ACHN cells by 24,
      48, and 72 h. as compared with control. Extracts induced a sub-G1 peak in flow
      cytometry histogram of treated cells indicating apoptotic cell death is involved
      in extracts induced-toxicity. Results imply that four herbal extracts inhibit the
      growth of ACHN cells as a concentration- and time-dependent manner. Also, results
      show that apoptosis is proposed as the possible mechanism of action. So, four
      herbal extracts could be considered as good anticancer agents in RCC after
      further studies.

PMID- 29201098
TI  - Exposing the Molecular Screening Method of Indonesian Natural Products Derivate
      as Drug Candidates for Cervical Cancer.
AB  - The menace of cervical cancer has reached an alarming rate. There are more than
      450.000 cases of cervical cancer yearly, with mortality rate of about 50%. This
      deadly cancer is caused by human papillomavirus (HPV), mainly subtypes 16 and 18.
      The pharmaceutical industry has produced drug for combating the virus, known as
      SAHA (suberoylanilide hydroxamic acid). It inhibits class II HDAC Homo sapiens
      (HDACi). The utilization of SAHA has some side effects, one of which is bone
      loss. Thus, searching for viable alternatives aside SAHA is inevitable. The
      objective of this research is to investigate the molecular interaction of
      selected Indonesian natural products with class II HDAC Homo sapiens. LigX tool
      in MOE 2008.10 was used as an instrument to investigate the molecular
      interaction. Then, computer-aided drug discovery and development (CADDD) approach
      involving molecular docking and dynamics methods was utilized to screen the
      natural products library. In the end, we found that herbaric acid could act as a
      potential drug candidate for cervical cancer.

PMID- 29201099
TI  - Synthesis and Biological Evaluation of Thiosemicarbazide Derivatives Endowed with
      High Activity toward Mycobacterium Bovis.
AB  - Thiosemicarbazides are potent intermediates for the synthesis of pharmaceutical
      and bioactive materials and thus, they are used extensively in the field of
      medicinal chemistry. The imine bond (-N=CH-) in this compounds are useful in
      organic synthesis, in particular for the preparation of heterocycles and non
      natural beta-aminoacids. In this paper the synthesis of some new
      thiosemicarbazide derivatives by condensation reaction of various aldehydes or
      ketones with 4-phenylthiosemicarbazide or thiosemicarbazide is reported. This
      synthesis method has the advantages of high yields and good bioactivity. The
      structures of these compounds were confirmed by IR, mass, 1H NMR, 13C NMR, and
      single-crystal X-ray diffraction studies. All of these compounds were tested for
      their in-vitro anti-mycobacterial activity. The influence of the functional group
      and position of substituent on anti-bacterial activity of compounds is
      investigated too. The preliminary results indicated that all of the tested
      compounds showed good activity against the test organism. The compounds 11 and 30
      showed the highest anti-tubercular activity (0.39 MUg/mL). This synthesis method
      has the advantages of high yields and good bioactivity.

PMID- 29201100
TI  - Single Step Purification of Novel Thermostable and Chelator Resistant Amylase
      from BacillusLicheniformis RM44 by Affinity Chromatography.
AB  - Bacillus licheniformis RM44 was isolated from hot spring near Karachi and
      screened for the production of extracellular amylase Amy RM44. Amy RM44 was
      purified to homogeneity on a single step by affinity chromatography using
      insoluble corn starch. The molecular weight of Amy RM44 was estimated to be 66
      kDa by SDS-PAGE and zymographic analysis. Nine fold purification was achieved
      with the specific activity of 870 U/mg that provides the total yield of the
      enzyme up to 31%. Studies on purified AmyRM44 characterization revealed that the
      optimum temperature of enzyme was 100 oC. Amy RM44 was proved to be highly
      thermostable as it retained 50% activity after 2 h at 100 oC. Amy RM44 was stable
      over wide range of pH with optimum activity at pH 5. Enzyme activity was not
      significantly inhibited by SDS and EDTA. Amy RM44 also exhibited its activity
      towards various carbohydrates such as dextrin, pullulan, alpha-cyclodextrin, beta
      cyclodextrin, and gamma-cyclodextrin.

PMID- 29201101
TI  - Interfering With Lipid Raft Association: A Mechanism to Control Influenza Virus
      Infection By Sambucus Nigra.
AB  - Sambucus nigra (elder) are broadly used species to treat microbial infections.
      The potential antiviral activity and mechanism action of elder fruit (EF) in
      human epithelium cell (A549) cultures infected with H9N2 influenza virus were
      determined. The effect of various concentrations of EF on influenza virus
      replication was examined by using virus titration, quantitative real time RT-PCR,
      fusion and lipid raft assays following two treatment procedures: A) pre-treated
      H9N2 virus with each concentration of EF extract and transfection of A549 cell
      cultures, and B) each concentrations of EF was added to H9N2 virus infected-cell
      cultures following virus adsorption. In both treatments with lower doses of EF
      increased viral titer as well as synthesized viral nucleoprotein as indicating
      the herb had no inhibitory effects on virus replication. In (B) trial with higher
      doses, 40 and 80 MUg/mL of EF, a significant decrease in virus titer and viral
      protein synthesis were shown in EF treated cells indicating the herb affect
      either entry of viruses or inhibition virus particle release. The results suggest
      that EF treatment of the influenza virus infected-human epithelial cells may
      involve in lipid raft association which function as platform for formation of
      viral membrane fusion and budding. Differencesin treatment time and dose of EF
      extract in infected cells with influenza virus have a marked effect on the
      efficacy of the herb.

PMID- 29201102
TI  - Enzymatic Analysis of Iranian Echis carinatus Venom Using Zymography.
AB  - Snakebite is a common problem especially in tropical areas all over the world
      including Iran. Echis carinatus as one of the most dangerous Iranian snakes is
      spreading in this country excluding central and northwest provinces. In this
      study gelatinase and fibrinogenolytic properties as two disintegrating matrix
      metalloproteinase enzymes were evaluated by a strong clear halo between 56-72 kDa
      in addition to another band located 76-102 kDa for gelatinase and one major band
      around 38 kDa for fibrinogenolytic enzyme respectively. The electrophorectc
      profile of our venom demonstrated at least one protein band between 24-31 kDa
      like previous reports and another two bands between 52-76 kDa and below 17 kDa
      stemmed probably due to the effect of natural selection in one species. According
      to our results Razi institute antivenin could neutralize in-vitro effects of
      gelatinase enzyme comprehensively. The electrophoretic profile of Iranian
      commercial antivenom as the main intravenous treatment of envenomed patients
      showed impurities in addition to F (ab')2 weighing 96 kDa in SDS-PAGE analysis.
      It proposes more efforts for refinement to avoid short and long unwanted effects
      in envenomed patients.

PMID- 29201103
TI  - Microbial Hydroxylation of 16alpha, 17alpha-Epoxyprogesterone by Penicillium
      Decumbens.
AB  - Microbial transformation has been successfully applied in the production of
      steroid intermediates with therapeutic use and commercial value in pharmaceutical
      industry due to its high regio- and stereo-selectivity. As such, it is still
      important to screen microbial strains with novel activity or more efficient
      abilities in the development of the commercial steroid industry.
      Biotransformation of steroid: 16alpha, 17alpha-epoxyprogesterone (1). using
      Penicilliumdecumbens as biocatalyst was investigated and selective hydroxylation
      of 1 was observed. The products were separated by silica gel column
      chromatography, and the structure determination was performed by MS, NMR, and X
      ray crystallography. Biotransformation of 1 afforded 7beta-hydroxy-16alpha,
      17alpha-epoxyprogesterone (2). and 7beta,11alpha-dihydroxy-16alpha,17alpha-
      epoxyprogesterone (3). The two novel metabolic products 2 and 3 were reported for
      the first time. Moreover, the identified C7beta- and C11-alphahydroxylation is a
      novel reaction of microbial transformation of steroids by P.decumbens.

PMID- 29201104
TI  - Biosynthesis, Characterization, Antimicrobial and Cytotoxic Effects of Silver
      Nanoparticles Using Nigella arvensis Seed Extract.
AB  - The biogenic synthesis of metal nanomaterial offers an environmentally benign
      alternative to the traditional chemical synthesis routes. In the present study,
      the green synthesis of silver nanoparticles (AgNPs) from aqueous solution of
      silver nitrate (AgNO3) by using Nigella arvensis L. seed powder extract (NSPE)
      has been reported. AgNPs were characterized by UV-vis absorption spectroscopy
      with an intense surface plasmon resonance band at 435 nm which reveals the
      formation of nanoparticles. Fourier transmission infrared spectroscopy (FTIR)
      showed that nanoparticles were capped with plant compounds. Transmission electron
      microscopy (TEM) showed silver nanoparticles, with a size of 2-15 nm, were
      spherical. The X-ray diffraction spectrum (XRD) pattern clearly indicates that
      AgNPs formed in the present synthesis were crystalline in nature. Stabilized
      films of exudate synthesized AgNPs were effective anti-bacterial agents. In
      addition, these biologically synthesized nanoparticles were also proved to
      exhibit excellent cytotoxic effect on a human breast cancer cell line (MCF-7) and
      a human colorectal adenocarcinoma cell line (HT-29). The results confirmed that
      the NSPE is a very good ecofriendly and nontoxic source for the synthesis of
      AgNPs as compared to the conventional chemical/physical methods. Therefore, N.
      arvensis seed provides future opportunities in nanomedicine by tagging
      nanoparticles with secondary metabolites.

PMID- 29201105
TI  - Synthesis, Characterization, and Biological Activity Studies on
      Fanlizhicyclopeptide A.
AB  - The synthesis of a proline-rich cyclic heptapeptide, fanlizhicyclopeptide A (8),
      previously isolated from the fruits of Annona squamosa (sugar-apples), is
      described via coupling of tetrapeptide -prolyl--tyrosyl--leucyl--proline methyl
      ester with tripeptide Boc-glycyl--valyl--proline followed by cyclization of the
      linear fragment having seven amino acid units. Structure of the synthesized
      cyclooligopeptide was confirmed by the means of chemical and spectroscopic
      methods including FTIR, 1H NMR, 13C NMR, FABMS and further, subjected to the
      anthelmintic, antibacterial and the antifungal activity studies. Bioactivity
      results indicated that the newly synthesized cyclic peptide displayed potent
      anthelmintic activity against the three earthworm species Megascoplex
      konkanensis, Pontoscotex corethruses and Eudrilus eugeniae at 2 mg/mL and
      remarkable anti-dermatophytic activities against Trichophyton mentagrophytes and
      Microsporum audouinii at concentration of 6 ug/mL.

PMID- 29201106
TI  - Expression of TolC and Organic Solvent Tolerance of Escherichia Coli
      Ciprofloxacin Resistant Mutants.
AB  - AcrAB-TolC is a major efflux pump in Escherichia coli. It was reported that tolC
      is overexpressed and involves in improving the organic solvent tolerance level in
      Escherichia colimarR mutants that are resistant to several antibiotics, such as
      ciprofloxacin. Low and intermediate levels resistance did not improve organic
      solvent tolerance. Thus, it was decided to measure tolC expression and organic
      solvent tolerance in high level ciprofloxacin resistant mutants. tolC expression
      was measured by real time PCR and organic solvent tolerance assay was conducted
      by counting bacterial colonies on LBGMg agar. Results showed that tolC expression
      was increased significantly (P<0.05) and organic solvent tolerance was slightly
      improved in high resistant mutants. It was concluded that high organic solvent
      tolerance may need higher expression of tolC.

PMID- 29201107
TI  - Selective activity of Oleanolic and Maslinic Acids on the Amastigote form of
      Leishmania Spp.
AB  - Leishmaniasis represents a serious threat to the health as one of the most
      important neglected tropical diseases as designated by the World Health
      Organization. The disease is endemic in 82 countries, among them Tunisia is an
      indigenous area for cutaneous Leishmaniasis. In a previous work, two tritepenic
      acids namely oleanolic and maslinic acids have been isolated from olive leaf
      extract. In the present paper, the in vitro activity against amastigotes stage of
      Leishmania (L.) infantum and Leishmania (L.) amazonensis was investigated.
      Maslinic acid showed the highest activity, against L. amazonensis, with an IC50
      of 1.417 +/- 0.401 ug/mL and a selectivity index of 9.405. Although, the
      oleanolic acid exhibit a better activity against L. infantum with an IC50 of
      0.999 +/- 0.089 ug/mL and selectivity index of 8.111.

PMID- 29201108
TI  - Truncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a
      TGF-beta Context Dependent Manner.
AB  - The Runt related transcription factors (RUNX) are recognized as key players in
      suppressing or promoting tumor growth. RUNX3, a member of this family, is known
      as a tumor suppressor in many types of cancers, although such a paradigm was
      challenged by some researchers. The TGF-beta pathway governs major upstream
      signals to activate RUNX3. RUNX3 protein consists of several regions and domains.
      The Runt domain is a conserved DNA binding domain and is considered as the main
      part of RUNX proteins. Herein, we compared the effects of Runt domains and full
      Runx3 in cell viability by designing two constructs of Runx3, including N
      terminal region and Runt domain. We investigated the effect of full-Runx3, N-t,
      and RD on growth inhibition in AGS, MCF-7, A549, and HEK293 cell lines which are
      different in TGF-beta sensitivity, in the absence and presence of TGF-beta. The
      full length RUNX3 did not notably inhibit growth of these cell lines while, the N
      t and RD truncates showed different trends in these cell lines. Cell
      proliferation in the TGF-beta impaired context cell lines (AGS and MCF-7)
      significantly decrease while in the A549 significantly increase. On the other
      hand, transfection of N-t and RD did not considerably affect the cell
      proliferation in the HEK293.Our results show that full-lenght RUNX3 did not
      affect the cell viability. Conversely, the N-t and RD constructs significantly
      changed cell proliferation. Therefore, therapeutic potentials for these truncated
      proteins are suggested in tumors with RUNX proteins dysfunction, even in the TGF
      beta impair context.

PMID- 29201109
TI  - Evaluation of Apoptosis in Multipotent Hematopoietic Cells of Bone Marrow by
      Anthracycline Antibiotics.
AB  - Anthracycline antibiotics are potent anticancer drugs widely used in the
      treatment of solid tumors and hematological malignancies. Because of their
      extensive clinical use and their toxic effect on normal cells, in the present
      study the effect of these drugs on multipotent hematopoietic bone marrow cells
      was investigated employing, viability tests, PARP cleavage, Hoechst 33258
      staining, DNA fragmentation and superoxide anion production techniques. The
      results revealed that daunorubicin and doxorubicin exhibited time and dose
      dependent cytotoxicity against the cells and upon increasing the drugs
      concentrations, apoptosis was occurred after 4 h of incubation and at low
      concentration of the drugs. The cleavage of poly ADP-ribose polymerase (PARP)
      demonstrated by daunorubicin and doxorubicin treatment of the cells, suggest that
      the apoptotic process is PARP dependent. The drugs induced DNA fragmentation and
      also anion superoxide production was increased upon rising drugs concentrations.
      From the results it is concluded that anthracycline antibiotics represent
      cytotoxic effect on hematopoietic progenitor/stem cells of bone marrow, inducing
      apoptosis and in this process toxicity of daunorubicin is more pronounced
      compared to doxorubicin.

PMID- 29201110
TI  - Presentation of a Novel Model for Evaluation of Commercialization of Research and
      Development: Case Study of the Pharmaceutical Biotechnology Industry.
AB  - The current situation in Iran suggests an appropriate basis for developing
      biotechnology industries, because the patents for the majority of hi-tech
      medicines registered in developed countries are ending. Biosimilar and technology
      oriented companies which do not have patents will have the opportunity to enter
      the biosimilar market and move toward innovative initiatives. The present
      research proposed a model by which one can evaluate commercialization of
      achievements obtained from research with a focus on the pharmaceutical
      biotechnology industry. This is a descriptive-analytic study where mixed
      methodology is followed by a heuristic approach. The statistical population was
      pharmaceutical biotechnology experts at universities and research centers in
      Iran. Structural equations were employed in this research. The results indicate
      that there are three effective layers within commercialization in the proposed
      model. These are a general layer (factors associated with management, human
      capital, legal infrastructure, communication infrastructure, a technical and
      executive infrastructures, and financial factors), industrial layer (internal
      industrial factors and pharmaceutical industry factors), and a third layer that
      included national and international aspects. These layers comprise 6 domains, 21
      indices, 41 dimensions, and 126 components. Compilation of these layers (general
      layer, industrial layer, and national and international aspects) can serve
      commercialization of research and development as an effective evaluation package.

PMID- 29201111
TI  - Cytokine Indexes in Pemphigus Vulgaris: Perception of Its Immunpathogenesis and
      Hopes for Non-Steroidal Treatment.
AB  - Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin,
      in which loss of adhesion between keratinocytes is caused by autoantibodies. It
      has been hypothesized that cytokines play an essential role in the pathogenesis
      of PV. This study aimed to investigate the other immunopathological aspects of PV
      by determining the serum levels of cytokines in PV patients to find another
      treatment strategy except corticosteroid therapy. Twenty-three patients with PV
      and a control group consisting of 24 healthy subjects were studied. Interleukin
      (IL)-2, IL-4, IL-6, IL10, IL-12, IL-17 and interferon-gamma (IFN-gamma) were
      measured in the sera of patients by the enzyme-linked immunosorbent assay (ELISA)
      method. The serum levels of IL-2, IL-4, IL-17 and IFN-gamma in most patients and
      controls were undetectable. The serum concentrations of IL-10 in the patients and
      controls were undetectable, nevertheless, the mean serum levels of this cytokine
      was 64.375 pg/mL in four patients. The mean serum levels of pro-inflammatory
      cytokine IL-6 increased significantly in the patients, compared to the controls
      (169.50 vs. 75.62 pg/mL) (P < 0.05). The same was observed for another pro
      inflammatory cytokine, IL-12 (135.33 vs. 86.28 pg/mL) (P < 0.05). Based on the
      results of this study it can be concluded that the Type 2 T helper cytokine (IL
      6) and macrophage-derived cytokine (IL-12) have essential roles in PV
      pathophysiology. In addition, the potential clinical application of Th1/Th2 type
      cytokine-based therapy in PV should be considered in next studies.

PMID- 29201113
TI  - Correlation between Rs2108622 Locus of CYP4F2 Gene Single Nucleotide Polymorphism
      and Warfarin Dosage in Iranian Cardiovascular Patients.

PMID- 29201112
TI  - Association of Warfarin Therapy with APOE and VKORC1 Genes Polymorphism in
      Iranian Population.
AB  - Warfarin is a vitamin K antagonist that genetic and non-genetic factors affected
      on its dose requirement in the patients with cardio vascular disease. The aim of
      this study was whether the APOE and VKORC1 polymorphisms influence on warfarin
      dose requirements in the part of Iranian patients. Blood samples were collected
      from 86 warfarin-treated patients. After extraction of genomic DNA, the VKORC1
      (rs9923231) and the APOE (rs429358 and rs7412) polymorphisms were genotyped by
      PCR-RFLP technique. We found that the Iranian patients carrying genotypes GA or
      AA of VKORC1 polymorphism tended to receive lower dose of warfarin (p = 0.018).
      Furthermore, the E3/E3 genotype was observed with the frequency more than 60% in
      the patients with low dose of warfarin. The BMI and weight also showed a positive
      correlation with warfarin dose. However, it was not statistically significant (p
      > 0.05). The results of this study may be useful in defining of warfarin dose
      algorithms for Iranian patients.

PMID- 29201114
TI  - Once Versus Thrice Daily Colistin in Critically Ill Ptients with Multi-Drug
      Resistant Infections.
AB  - : The aim of this study was to evaluate the procalcitonin (PCT) changes in two
      different high-dose colistin regimens in the treatment of multi-drug resistant
      MDR gram negative infections in ICU patients. This is a prospective study of
      adult ICU patients with bacteremia and ventilator associated pneumonia (VAP)
      caused by MDR gram negative pathogens. Patients were assigned to two colistin
      administration groups. Group A received 9 and group B received 3 million
      international units every 24 and 8 h respectively. Baseline characteristics and
      measurements of PCT concentrations at the start, the 3rd and the 5th day of the
      antibiotic therapy and their trends between the two groups were recorded and
      compared. of 40 patients enrolled, 34 completed the study protocol, of whom 30
      (88.2%) had (VAP) and 4 (11.8%) had bacteremia. There were no statistically
      significant differences in the baseline characteristics between the two groups.
      The mean PCT levels in two study groups were; 2.34, 1.24, and 0.95 in group A and
      5.89, 1.24 and 0.8 in group B at the baseline, 3rd and 5th day of colistin
      administration respectively (P=0.47). The ICU length of stay (LOS) in days and
      ICU mortality were; 31.31, 35.3% and 32.06, 22.2% in groups A and B (P=0.39,
      0.87), respectively. CONCLUSION: We did not find any statistically significant
      differences in the serum PCT levels, ICU LOS or ICU mortality, between the two
      groups, who received maximum recommended dose of CMS with 2 different intervals
      of every 8 or 24 h.

PMID- 29201115
TI  - Effect of Vitamin D Supplementation on Procalcitonin as Prognostic Biomarker in
      Patients with Ventilator Associated Pneumonia Complicated with Vitamin D
      Deficiency.
AB  - Ventilator-associated pneumonia (VAP) is a common and serious problem that
      develops after more than 48 h of mechanical ventilation. Improving the activity
      of immune system with vitamin D, and its consequent impact on prognostic
      biomarkers of VAP was studied in the current study. A randomized double blind
      placebo controlled clinical trial was designed. A total of 46 patients with VAP,
      who were suffering from vitamin D deficiency, were randomly allocated into the
      study groups of placebo (n=22) and treatment (n=24) The treatment group received
      300,000 units of intramuscular vitamin D. Serum levels of procalcitonin and
      vitamin D along with SOFA and CPIS scores were determined at baseline and on day
      7 after intervention. The mortality rate of patients was also monitored for the
      succeeding 28 days after the injection. The administration of vitamin D
      significantly enhanced its levels (P<0.0001) in the treated patients (12.28 +/-
      8.26) in comparison to placebo group (1.15 +/- 1.50). The levels of PCT were
      significantly decreased (p=0.001) in the treatment group (- 0.02 +/- 0.59 ng/mL)
      compared to that of placebo group (0.68 +/- 1.03 ng/mL). However, changes in
      (SOFA) and CPIS scores were not significantly different between study groups
      (p=0.63 and p=0.32, respectively). Interestingly, the mortality rate of patients
      in the treatment group (5/24) was significantly lower (p=0.04) than that of the
      placebo group (11/22). In conclusion, our results indicate that vitamin D
      supplementation can significantly reduce the procalcitonin in (VAP) patients, and
      must be considered as a preventive and/or therapeutic strategy.

PMID- 29201116
TI  - Fluoxetine Regulates Ig Kappa Chain C Region Expression Levels in the Serum of
      Obsessive-Compulsive Disorder Patients: A proteomic Approach.
AB  - Obsessive-Compulsive Disorder (OCD) is one of the most common mental conditions.
      Proteome profiling may help identifying important proteins and finally shed
      lights to complexity of OCD underlying mechanisms. Here, by the application gel
      based proteomic approach the proteome profile of patients with washing subtype of
      OCD before and after treatment with Fluoxetine (positive responders) are compared
      to healthy matched controls. However, only one of the differentially expressed
      proteins is examined and introduced in this paper. Proteomic analysis was done by
      the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE),
      combined with (MALDI-TOF-TOF MS)-based. Furthermore, network analysis and
      biological annotation were handled by Cytoscape Plug-in and CluePedia. The
      proteome comparison between groups identified protein with the significant
      expression changes (p<0.05 and fold change >= 1.5). While the expression level of
      Ig Kappa Chain C Region is significantly decreased in OCD patients before any
      treatments, the trend is almost normalized after treatment with Fluoxetine in
      positive responders. In addition, interaction profile of IGKC shows that the
      interacting proteins may be affected as the expression pattern of IGKC changes in
      OCD patients. In conclusion, IGKC may be introduced as potential biomarker in our
      study; yet, investigation in bigger sample size and application of validation
      methods is a requirement.

PMID- 29201117
TI  - The Effect of Baby Walker on Child Development: A Systematic Review.
AB  - Objective: Baby walkers are used all around the world as fun equipment without
      any dangers. In contrast with public beliefs, some researchers have claimed they
      can cause developmental delay. We aimed to investigate their effect on child
      development through a systematic review. Materials & Methods: We searched PubMed,
      Google Scholar, EMBASE, and Scopus for related articles in English and included
      all study designs. All articles, which fulfilled the inclusion criteria, were
      included without considering the year of publication. Results: Of 315 articles
      found in PubMed, 1630 citations in Google Scholar, 18 articles in EMBASE, and 38
      papers in Scopus, only 9 articles fulfilled the inclusion criteria. Among them, a
      cohort study and two cross-sectional studies reported developmental delay in
      thaspects in baby walker users. Other studies including clinical trials did not
      show any developmental delay in these children. Conclusion: Evidence against baby
      walker is not enough regarding its negative effect on child development. This
      subject needs to be addressed more, considering a large number of baby walker
      users worldwide.

PMID- 29201118
TI  - Duchenne Muscular Dystrophy (DMD) Protein-Protein Interaction Mapping.
AB  - Objective: Duchenne muscular dystrophy (DMD) is one of the mortal diseases,
      subjected to study in terms of molecular investigation. In this study, the
      protein interaction map of this muscle-wasting condition was generated to gain a
      better knowledge of interactome profile of DMD. Materials & Methods: Applying
      Cytoscape and String Database, the protein-protein interaction network was
      constructed and the gene ontology of the constructed network was analyzed for
      biological process, molecular function, and cellular component annotations.
      Results: Among 100 proteins related to DMD, dystrophin, utrophin, caveolin 3, and
      myogenic differentiation 1 play key roles in DMD network. In addition, the gene
      ontology analysis showed that regulation processes, kinase activity, and
      sarcoplasmic reticulum were the highlighted biological processes, molecular
      function, and cell component enrichments respectively for the proteins related to
      DMD. Conclusion: The central proteins and the enriched ontologies can be
      suggested as possible prominent agents in DMD; however, the validation studies
      may be required.

PMID- 29201119
TI  - Fordyce Happiness Program and Performance for Mothers of Children with Cleft Lip
      and Palate Referring Healthcare Team in Isfahan University of Medical Sciences in
      2015.
AB  - Objective: The present study was conducted to investigate the effect of happiness
      program on performance for mothers of children with cleft lip and palate.
      Materials & Methods: In this semi experimental study, 64 mothers of children with
      cleft lip and palate referring healthcare team in Isfahan University of Medical
      Sciences, Iran were enrolled by simple random sampling in 2015. They were divided
      to two groups of control and intervention. Then, the program of happiness
      training was implemented within 10 sessions of two hours each and performance
      questionnaire were filled out prior two months after the last session. The data
      were analyzed by paired t-test, independent t-test, chi-square and Mann-Whitney.
      Results: Mean age of the mothers in intervention and control groups was 33.3+/
      6.3 and 33.5+/-5.8 yr, respectively. Mean age of the children in intervention and
      control groups was 6.34+/-3.37 and .03+/-3.36 yr, in that order. No significant
      difference was seen on demographic variables between the two groups. Besides, no
      significant difference was noticed on mean score of performance domains in the
      two groups before training. However, after 2 months a significant difference on
      mean score of performance domains was observed (P<0.000). Intervention group
      showed significant differences on mean score of performance domains before and
      after intervention (P<0.000). However, the control group had no significant
      change. Conclusion: Given the effect of happiness, program in promoting mothers
      performance for children with cleft lip and palate, this program can be used in
      healthcare centers to empower mothers and enhance performance in taking care of
      children.

PMID- 29201121
TI  - Assessment of Toxoplasma Seropositivity in Children Suffering from Anxiety
      Disorders.
AB  - Objective: This study aimed to assess the seroprevalence of Toxoplasma gondii in
      children with anxiety disorders. Materials & Methods: This cross-sectional study
      was conducted between Sep 2012 and May 2013 in Pediatrics Clinic of Baqiyatallah
      Hospital, Tehran, Iran. Children were assessed clinically. Diagnosis of patients
      with anxiety disorders was based on DSM-4 system, performed by child
      psychiatrist. Then their anti-Toxoplasma antibodies were measured. A
      questionnaire was verbally administered to all individuals' parents including
      demographic information and questions about life style, family history, medical
      history, economic situation, residence, nutritional patterns and contact with
      animals. Results: Ninety-six male and female cases with a mean age of 8.56+/-2.5
      and 8.42+/-1.9 yr underwent analysis. Anti- T. gondii IgG antibody was found in
      one case of each group. There was no significant difference between case and
      control groups for serum Toxoplasma IgG antibody (P=0.14). No case individuals
      had Anti- T. gondii IgM antibody, while it was found in one control individual.
      No significant difference was seen between case and control groups for Toxoplasma
      IgM antibody (P=0.27). Conclusion: Toxoplasmosis has no direct effect on the
      incidence of anxiety disorders. More studies are needed with a larger volume of
      individuals in future.

PMID- 29201120
TI  - Long-term Video-EEG Monitoring Findings in Children and Adolescents with
      Intractable Epilepsy.
AB  - Objective: Long Term Video-EEG Monitoring (LTM) may give us important information
      in the preoperative assessment of these patients. We performed this study for the
      first time in pediatric age group in Iran. Materials and Methods: In this cross
      sectional study, 43 children between 4 to 18 yr, with intractable epilepsy
      referred to Shefa Neuroscience Research Center, Tehran, Iranfrom2007-2012, were
      enrolled to study in order to evaluate their long-term video EEG findings.
      Results: The patients mean age was10.07 yr, from which 24(65.9%) were boys.Seven
      patients with definite epileptogenic zone were advised to perform lesionectomy
      surgery.In two patients, there was not any seizure onset focus but corpus
      callosotomy was advised to control their frequent falling.Eight cases were
      recommended to perform electrocorticography or invasive EEG monitoring and26
      cases to adjust medical treatment. In three cases, there was not any electrical
      seizure activity during clinical attacks, so discontinuing anti-epileptic drugs
      were recommended fordiagnosis of conditions that mimic epilepsy. Conclusion: It
      is necessary to perform LTM in patients with refractory epilepsy in order to
      determine their treatment strategy. If there is any doubt about pseudoseizureLTM
      can help to differentiate epilepsy from conditions that mimic epilepsy.

PMID- 29201122
TI  - Quasi-experimental Effectiveness of Cognitive-behavioral Therapy on Reliving
      Migraine Headaches in Migraine Sufferers.
AB  - Objective: This study aimed to investigate the effectiveness of cognitive
      behavioral therapy on relieving migraine headaches in migraine sufferers.
      Materials & Methods: In this quasi-experimental study with pre-test and post-test
      method, the samples were outpatients of public hospitals in Ilam City,
      southwestern Iran since May-Jul 2010. They were selected based on inclusion and
      exclusion criteria, and divided into experimental and control groups. The data
      were analyzed using SPSS ver. 16 and via multivariate covariance method. Results:
      Cognitive-behavioral therapy affected on reducing the duration of symptoms of
      migraine in sufferers (P<0.05). Conclusion: Cognitive behavioral therapy effects
      on reducing the time duration of symptoms of migraine headaches. Thistherapeutic
      method increases the level of individual, familial, social and occupational
      activities by reducing the time duration of symptoms and this method helps the
      individuals to resume their activities and regain their previous control instead
      of founding themselves incapable and helpless due to the pain they suffer from.

PMID- 29201123
TI  - The Effect of Kinesio Taping on Handgrip and Active Range of Motion of Hand in
      Children with Cerebral Palsy.
AB  - Objective: Kinesio taping is a relatively new technique, which uses in
      rehabilitation of neurologic diseases. The aim of this study was to investigate
      the effects of Kinesio taping on hand grip and active range of motion of hand in
      children with cerebral palsy (CP). Materials and Methods: In this experimental
      study with pre-test and three post-tests, 32 children with CP randomly were
      placed in experimental (n=17) and control group (n=15).Kinesio taping was applied
      on dorsum of forearm and hand. Evaluation was performed initially, two days after
      taping and two days after tape removal. Goniometer was used to evaluate active
      range of motion of wrist extension. In addition, vigorimeter was used to evaluate
      of grip strength. Results: In pre-test, there was no difference between groups
      but in post-tests; initially after application of taping with P<0.05, two days
      after application of taping with P<0.05 and follow-up (two days after removed
      taping) with P<0.05 were significant differences between trial and control group.
      Conclusion: Kinesio taping in neurorehabilitation of children with CP can be a
      useful option to promote power or grip strength and active range of motion of
      wrist and thumb.

PMID- 29201124
TI  - Does Parent Report Gross Motor Function Level of Cerebral Palsy Children Impact
      on the Quality of Life in these Children?
AB  - Objective: The aim of this study was to assess the effect of parent report gross
      motor function level of cerebral palsy (CP) children on the parent report quality
      of life of CP children. Materials & Methods: Sampling of this cross-sectional
      study was done in occupational therapy clinics and CP children's schools in 2016
      in Zanjan, Iran. Samples size was 60 CP children aged 6-12 yr and for sampling
      method, a non-probability convenience was used. For assessing the quality of life
      of CP children the cerebral palsy quality of life (CP QOL) questionnaire and for
      assessing the level of gross motor function of CP children the Gross Motor
      Function Classification System Family Report Questionnaire (GMFCSFRQ) were used.
      Results: The average age of children (22 males and 30 females) was 8.92 yr old
      (minimum 6 yr and maximum 12 yr). The relationship between the level of gross
      motor function and participation and physical health was direct and significant
      (r=0.65). The relationship between functioning, access to services and family
      health with the level of gross motor function was direct but was not significant
      (P>0.05) and the relationship between pain and impact of disability and emotional
      well-being with the level of gross motor function was significant (P<0.05).
      Conclusion: There was no strong correlation between the level of gross motor
      function and quality of life of children with cerebral palsy. It means that the
      level of gross motor function cannot be used as a predictor of quality of life
      for children with cerebral palsy alone.

PMID- 29201125
TI  - Glutaric AciduriaType 1: Clinical and Molecular Study in Iranian Patients, 3
      Novel Mutations.
AB  - Objective: Glutaricaciduria type 1 (GA1), is a rare, treatable neuro metabolic
      disease, due to glutaryl- CoA dehydrogenase (GCDH) gene mutation.In regions
      without neonatal blood screening (NBS), patients are diagnosed in symptomatic
      period. This study was carried out to assess patients with GA1 for clinical,
      biochemical, neuroimaging findings and GCDH gene mutations analysis. Materials &
      Methods: In this cross-sectional study, clinical manifestation, neuroimaging and
      metabolic findings of eleven Iranian GA1 patients of MofidChildren's Hospital,
      Tehran, Iranbetween 2001 and 2011,were evaluated.Mutational analysis of the GCDH
      gene was performed on genomic DNA. Genomic DNA was extracted from peripheral
      lymphocytes using QIAamp DNA Micro Kit (Qiagen). All 11 exons and flanking
      intronic regions of the GCDH gene were amplified by polymerase chain reaction
      (PCR). Results: All patients were diagnosed before 32 months old. Clinical
      presentations of GA1 include acute encephalopathic crisis and/or developmental
      delay and macrocephaly. Seven GCDH gene mutations were detected in our patients.
      The most frequent GCDH mutations occurred in exon7 then exon8, 10 and11. G244 C
      in exon7, R294 Q in exon8 and N373 S in exon 10 were three novel mutations. There
      was no correlation between of genotype and phenotype in our patients. Conclusion:
      Physician must remember GA1 in differential diagnosis of acute encephalopathic
      crisis, macrocephaly, developmental delay, movement disorders such as dystonia
      and dyskinesia. Early detection, proper treatment and selective screening of
      patients' siblings can prevent neurologic disabilities.

PMID- 29201126
TI  - Neurological Crises after Discontinuation of Nitisinone (NTBC) Treatment in
      Tyrosinemia.
AB  - Objective: Tyrosinemia type 1 is a hereditary disorder with liver, kidney and
      nervous system involvement. Neurological crises can occur in tyrosinemic patients
      without treatment or when treatment stops. Here we report three children that
      developed diaphragmatic paralysis after discontinuation of nitisinone. In
      patients with tyrosinemia type 1, combined treatment with nitisinone and a low
      tyrosine diet have prevented neurological crises. The purpose of this article was
      to express the importance of taking nitisinone (NTBC) for tyrosinemia diseases
      and risks of inadvertent discontinuation. Materials & Methods: We describe three
      children referred to emergency department of Nemazee Hospital, Shiraz, Iran in
      December 2015 with tyrosinemia type 1 who stopped NTBC treatment, presenting with
      respiratory. Clinical findings, laboratory results, and imaging study were
      assessed in three patients on admission and after starting nitisinone. Results:
      All patients developed diaphragmatic paralysis and respiratory distress after
      interruption of nitisinone treatment. Two of the patients were improved after
      starting nitisinone. One patient expired due to respiratory failure. Full
      recovery occurred about 2 months after starting nitisinone. Conclusion:
      Discontinuation of nitisinone can induce diaphragmatic paralysis and respiratory
      failure. Therefore, we should advise patients to use NTBC for the long term and
      not interrupt it.

PMID- 29201127
TI  - Another Limping Child: An Interesting Diagnosis Journey.
AB  - Limp is described as any deviation from a normal gait pattern for the child's
      age. Limping takes many forms and is one of the most enigmatic complaints in
      pediatric medicine. It is never normal, and both benign and life-threatening
      illnesses can present with limp. The provisional diagnosis can be a challenge to
      establish even after history, physical, and laboratory examinations.

PMID- 29201128
TI  - A Highlighted Case for Emphasizing on Clinical Diagnosis for Rare Syndrome in
      Third World.
AB  - Premature tooth loss is a disastrous situation that affects deciduous or
      permanent teeth era with different causes. It may be attributed to some disorders
      like Papillon-Lefevre syndrome or coffin-lowry syndrome but because of ambiguous
      nature, precise diagnosis is not easily possible. Moreover, it has very low
      incidence and defines by few and limited case series, with vague characters to
      some extent, confusion in detecting the right diagnosis is a common possibility.
      Hence, it is expectable to have a wrong diagnosis for this case. In this study, a
      5-yr-old boy with chief complaint of early tooth loss despite having blindness in
      left eye and palmar keratosis is reported, although he had some other
      manifestation of oculodentodigital dysplasia (ODDD) like ataxia, dysarthria and
      nail deformity, ignoring other extra and intra oral finding. He was diagnosed as
      Papillon-Lefevre syndrome already, just because of early tooth loss and palmar
      keratosis.

PMID- 29201129
TI  - Cerebral Vasculitis in a Case of Meningitis.
AB  - Cerebral vasculitis is a serious complication of meningitis with Streptococcus
      pneumoniae. We report a 5 yr old girl who was admitted in May 2015 at Fortis
      Hospital, Kolkata, India and was diagnosed to have pneumococcal meningitis with
      vasculitis on DWMRI within a week of onset of fever. She was given high dose of
      methyl-prednisolone simultaneously with antibiotics and successfully treated
      without any neuro-sequelae. Although vasculitis has been documented to develop as
      sequelae to bacterial meningitis usually in the second week, our patient had an
      early presentation. Treatment with high dose steroid along with antibiotics
      resulted in dramatic improvement with no neurodeficit. DW-MRI is an important
      investigation to pick up early, evidence of vasculitis in a patient with
      meningitis who is showing neurological deteriorations despite improvement in
      blood parameters.

PMID- 29201130
TI  - Flexible semiparametric joint modeling: an application to estimate individual
      lung function decline and risk of pulmonary exacerbations in cystic fibrosis.
AB  - Background: Epidemiologic surveillance of lung function is key to clinical care
      of individuals with cystic fibrosis, but lung function decline is nonlinear and
      often impacted by acute respiratory events known as pulmonary exacerbations.
      Statistical models are needed to simultaneously estimate lung function decline
      while providing risk estimates for the onset of pulmonary exacerbations, in order
      to identify relevant predictors of declining lung function and understand how
      these associations could be used to predict the onset of pulmonary exacerbations.
      Methods: Using longitudinal lung function (FEV1) measurements and time-to-event
      data on pulmonary exacerbations from individuals in the United States Cystic
      Fibrosis Registry, we implemented a flexible semiparametric joint model
      consisting of a mixed-effects submodel with regression splines to fit repeated
      FEV1 measurements and a time-to-event submodel for possibly censored data on
      pulmonary exacerbations. We contrasted this approach with methods currently used
      in epidemiological studies and highlight clinical implications. Results: The
      semiparametric joint model had the best fit of all models examined based on
      deviance information criterion. Higher starting FEV1 implied more rapid lung
      function decline in both separate and joint models; however, individualized risk
      estimates for pulmonary exacerbation differed depending upon model type. Based on
      shared parameter estimates from the joint model, which accounts for the nonlinear
      FEV1 trajectory, patients with more positive rates of change were less likely to
      experience a pulmonary exacerbation (HR per one standard deviation increase in
      FEV1 rate of change = 0.566, 95% CI 0.516-0.619), and having higher absolute FEV1
      also corresponded to lower risk of having a pulmonary exacerbation (HR per one
      standard deviation increase in FEV1 = 0.856, 95% CI 0.781-0.937). At the
      population level, both submodels indicated significant effects of birth cohort,
      socioeconomic status and respiratory infections on FEV1 decline, as well as
      significant effects of gender, socioeconomic status and birth cohort on pulmonary
      exacerbation risk. Conclusions: Through a flexible joint-modeling approach, we
      provide a means to simultaneously estimate lung function trajectories and the
      risk of pulmonary exacerbations for individual patients; we demonstrate how this
      approach offers additional insights into the clinical course of cystic fibrosis
      that were not possible using conventional approaches.

PMID- 29201131
TI  - The male sexual apparatus in the order Scorpiones (Arachnida): a comparative
      study of functional morphology as a tool to define hypotheses of homology.
AB  - Background: Insemination in scorpions is carried out by means of a partly
      sclerotized structure, the spermatophore, which is composed of two separate
      halves, the hemispermatophores. In most genera these reproductive structures can
      be used to differentiate species. However, many taxa such as the genus Euscorpius
      and the family Diplocentridae lack the morphological diversity observed in the
      copulatory organs of many other arthropods, rendering them useless for species
      level taxonomy. Such structural stasis, however, suggests that hemispermatophores
      have evolved relatively slowly and may thus provide a stronger phylogenetic
      signal for recognizing supra-generic ranks than previously thought. Based on the
      postulate that the phenotypic stability observed in some groups is the
      consequence of functional constraint, the most comprehensive comparative study of
      the male sexual apparatus to date was conducted for a complete reassessment of
      the morphology, phylogenetic value and hypotheses of homology of these
      structures. Results: Hemispermatophores, pre- and post-insemination
      spermatophores, as well as the inherent mechanisms of insemination, were studied
      across the whole order, allowing the recognition and description of a series of
      five basic bauplans for the capsular region. For the most part, these patterns
      appear to be consistent within each major taxonomic group, but several cases of
      incongruence between spermatophore morphology and taxonomy raises questions about
      the monophyly of some clades. The Bothriuridae are traditionally regarded as a
      basal scorpionoid family. However, except for the genus Lisposoma, bothriurid
      hemispermatophores and spermatophores are morphologically more similar to those
      of the Chactoidea than to those of scorpionoids. On the other hand, the male
      copulatory structures of the hormurid clade (Hormiops (Hormurus + Liocheles)) are
      more akin to those of Diplocentridae and Heteroscorpionidae than to those of
      other hormurids. Conclusions: Spermatophore capsular patterns appears to be
      congruent with a recent phylogeny of the order Scorpiones based on phylogenomic
      data that placed Bothriuridae outside of Scorpionoidea and Liocheles outside of
      Hormuridae, in contradicton with earlier phylogenetic reconstructions based on
      morphology. This raises questions about the potential use of functionally
      constrained traits to assess the reliability of contradicting phylogenetic
      hypotheses and emphasizes the need for a thorough reassessment of the scorpion
      phylogenetic relationships.

PMID- 29201132
TI  - A multilevel longitudinal study of obsessive compulsive symptoms in adolescence:
      male gender and emotional stability as protective factors.
AB  - The severity of obsessive compulsive symptoms (OCS) is suggested to be normally
      distributed in the general population, and they appear to have an impact on a
      range of aspects of adolescent development. Importantly, there are individual
      differences regarding susceptibility to OCS. In the present repeated measures
      study, OCS were studied in relation to gender and emotional stability (as a
      personality trait) using a normative sample of 515 adolescents at ages 16 and 18
      years. OCS were assessed with the relevant subscale of the SCL-90-R and emotional
      stability with the Five Factor Questionnaire. A three-level hierarchical linear
      model was calculated to longitudinally assess the over time variations of OCS and
      their over time links to gender and emotional stability, while controlling for
      random effects due to the nesting of the data. Experiencing OCS increased with
      age (between 16 and 18 years). Additionally, male gender and higher emotional
      stability were associated with lower OCS at 16 years and these remained stable
      over time. Results indicate age-related and between individual differences on
      reported OCS that need to be considered for prevention and intervention planning.

PMID- 29201133
TI  - Risk of lymphoma subtypes by occupational exposure in Southern Italy.
AB  - Background: Occupational exposure is known to play a role in the aetiology of
      lymphomas. The aim of the present work was to explore the occupational risk of
      the major B-cell lymphoma subtypes using a case-control study design. Methods:
      From 2009 to 2014, we recruited 158 lymphoma cases and 76 controls in the
      provinces of Bari and Taranto (Apulia, Southern Italy). A retrospective
      assessment of occupational exposure based on complete work histories and the
      Carcinogen Exposure (CAREX) job-exposure matrix was performed. Results: After
      adjusting for major confounding factors, farmers showed an increased risk of
      diffuse large B-cell lymphoma (DLBCL) [odds ratio (OR) = 10.9 (2.3-51.6)] and
      multiple myeloma (MM) [OR = 16.5 (1.4-195.7)]; exposure to the fungicide Captafol
      was significantly associated with risk of non-Hodgkin lymphoma (NHL) [OR = 2.6
      (1.1-8.2)], particularly with the risk of DLBCL [OR = 5.3 (1.6-17.3)].
      Conclusions: Agricultural activity seems to be a risk factor for developing
      lymphoma subtypes, particularly DLBCL, in the provinces of Bari and Taranto
      (Apulia Region, Southern Italy). Exposure to the pesticides Captafol, Paraquat
      and Radon might be implicated. Trial registration: Protocol number UNIBA
      2207WEJLZB_004 registered 22/09/2008.

PMID- 29201134
TI  - Multi-feature machine learning model for automatic segmentation of green
      fractional vegetation cover for high-throughput field phenotyping.
AB  - Background: Accurately segmenting vegetation from the background within digital
      images is both a fundamental and a challenging task in phenotyping. The
      performance of traditional methods is satisfactory in homogeneous environments,
      however, performance decreases when applied to images acquired in dynamic field
      environments. Results: In this paper, a multi-feature learning method is proposed
      to quantify vegetation growth in outdoor field conditions. The introduced
      technique is compared with the state-of the-art and other learning methods on
      digital images. All methods are compared and evaluated with different
      environmental conditions and the following criteria: (1) comparison with ground
      truth images, (2) variation along a day with changes in ambient illumination, (3)
      comparison with manual measurements and (4) an estimation of performance along
      the full life cycle of a wheat canopy. Conclusion: The method described is
      capable of coping with the environmental challenges faced in field conditions,
      with high levels of adaptiveness and without the need for adjusting a threshold
      for each digital image. The proposed method is also an ideal candidate to process
      a time series of phenotypic information throughout the crop growth acquired in
      the field. Moreover, the introduced method has an advantage that it is not
      limited to growth measurements only but can be applied on other applications such
      as identifying weeds, diseases, stress, etc.

PMID- 29201135
TI  - Measuring Coupling of Rhythmical Time Series Using Cross Sample Entropy and Cross
      Recurrence Quantification Analysis.
AB  - The aim of this investigation was to compare and contrast the use of cross sample
      entropy (xSE) and cross recurrence quantification analysis (cRQA) measures for
      the assessment of coupling of rhythmical patterns. Measures were assessed using
      simulated signals with regular, chaotic, and random fluctuations in frequency,
      amplitude, and a combination of both. Biological data were studied as models of
      normal and abnormal locomotor-respiratory coupling. Nine signal types were
      generated for seven frequency ratios. Fifteen patients with COPD (abnormal
      coupling) and twenty-one healthy controls (normal coupling) walked on a treadmill
      at three speeds while breathing and walking were recorded. xSE and the cRQA
      measures of percent determinism, maximum line, mean line, and entropy were
      quantified for both the simulated and experimental data. In the simulated data,
      xSE, percent determinism, and entropy were influenced by the frequency
      manipulation. The 1 : 1 frequency ratio was different than other frequency ratios
      for almost all measures and/or manipulations. The patients with COPD used a 2 : 3
      ratio more often and xSE, percent determinism, maximum line, mean line, and cRQA
      entropy were able to discriminate between the groups. Analysis of the effects of
      walking speed indicated that all measures were able to discriminate between
      speeds.

PMID- 29201137
TI  - Development and challenges of palliative care in Indonesia: role of psychosomatic
      medicine.
AB  - Purpose of review: To summarize the current status of palliative care and the
      role of psychosomatic medicine in Indonesia. Recent findings: Palliative care is
      not a new issue in Indonesia, which has been improving palliative care since 1992
      and developed a palliative care policy in 2007 that was launched by the
      Indonesian Ministry of Health. However, the progress has been slow and varied
      across the country. Currently, palliative care services are only available in a
      few major cities, where most of the facilities for cancer treatment are located.
      Psychosomatic medical doctors have advantages that contribute to palliative care
      because of their special training in communication skills to deal with patients
      from the standpoints of both mind and body. Summary: Palliative care services in
      Indonesia are established in some hospitals. Future work is needed to build
      capacity, advocate to stakeholders, create care models that provide services in
      the community, and to increase the palliative care workforce. Psychosomatic
      medicine plays an important role in palliative care services.

PMID- 29201136
TI  - Depolarization signatures map gold nanorods within biological tissue.
AB  - Owing to their electromagnetic properties, tunability and biocompatibility, gold
      nanorods (GNRs) are being investigated as multifunctional probes for a range of
      biomedical applications. However, detection beyond the reach of traditional
      fluorescence and two-photon approaches and quantitation of their concentration in
      biological tissue remain challenging tasks in microscopy. Here we show how the
      size and aspect ratio that impart GNRs with their plasmonic properties also make
      them a source of entropy. We report on how depolarization can be exploited as a
      strategy to visualize GNR diffusion and distribution in biologically relevant
      scenarios ex vivo, in vitro and in vivo. We identify a deterministic relation
      between depolarization and nanoparticle concentration. As a result, some of the
      most stringent experimental conditions can be relaxed, and susceptibility to
      artefacts is reduced, enabling microscopic and macroscopic applications.

PMID- 29201138
TI  - Implementation and use of cloud-based electronic lab notebook in a bioprocess
      engineering teaching laboratory.
AB  - Background: Electronic lab notebooks (ELNs) are better equipped than paper lab
      notebooks (PLNs) to handle present-day life science and engineering experiments
      that generate large data sets and require high levels of data integrity. But
      limited training and a lack of workforce with ELN knowledge have restricted the
      use of ELN in academic and industry research laboratories which still rely on
      cumbersome PLNs for recordkeeping. We used LabArchives, a cloud-based ELN in our
      bioprocess engineering lab course to train students in electronic record keeping,
      good documentation practices (GDPs), and data integrity. Results: Implementation
      of ELN in the bioprocess engineering lab course, an analysis of user experiences,
      and our development actions to improve ELN training are presented here. ELN
      improved pedagogy and learning outcomes of the lab course through stream lined
      workflow, quick data recording and archiving, and enhanced data sharing and
      collaboration. It also enabled superior data integrity, simplified information
      exchange, and allowed real-time and remote monitoring of experiments. Several
      attributes related to positive user experiences of ELN improved between the two
      subsequent years in which ELN was offered. Student responses also indicate that
      ELN is better than PLN for compliance. Conclusions: We demonstrated that ELN can
      be successfully implemented in a lab course with significant benefits to
      pedagogy, GDP training, and data integrity. The methods and processes presented
      here for ELN implementation can be adapted to many types of laboratory
      experiments.

PMID- 29201139
TI  - Structural properties of starch-chitosan-gelatin foams and the impact of gelatin
      on MC3T3 mouse osteoblast cell viability.
AB  - Background: This study examines the effects of adding gelatin to a starch
      chitosan composite foam, focusing on the altered structural and biological
      properties. The compressive modulus of foams containing different gelatin
      concentrations was tested in dry, wet, and lyophilized states. MC3T3 mouse
      osteoblast cells were used to test the composite's ability to support cell
      growth. The stability of the foams in alpha-MEM culture media with and without
      cells was also examined. Results: It was found that for dry foams, the
      compressive modulus increased with increasing gelatin content. For foams tested
      in wet and lyophilized states, the compressive modulus peaked at a gelatin
      concentration of 2.5% and 5%, respectively. The growth of MC3T3 mouse osteoblast
      cells was tested on the foams with different gelatin concentrations. The addition
      of gelatin had a positive effect on the cell growth and proliferation.
      Conclusion: The composite foam containing gelatin improved cell growth and is
      only dissolved by the growing cells at a rate influenced by the initial
      concentration of gelatin added to the foam.

PMID- 29201140
TI  - Expression of the entire polyhydroxybutyrate operon of Ralstonia eutropha in
      plants.
AB  - Background: Previously we demonstrated that an entire bacterial operon (the PRN
      operon) is expressible in plants when driven by the Tomato -yellow-leaf-curl
      virus (TYLCV) -derived universal vector IL-60.Petroleum-derived plastics are not
      degradable, and are therefore harmful to the environment. Fermentation of
      bacteria carrying operons for polyhydroxyalkanoates (PHAs) produces degradable
      bioplastics which are environmentally friendly. However, bacterial production of
      bioplastics is not cost-effective, and attention is turning to their production
      in plants. Such "green" plastics would be less expensive and environmentally
      friendly. Hence, attempts are being made to substitute petroleum-derived plastics
      with "green" plastics. However, transformation of plants with genes of operons
      producing bioplastics has deleterious effects. Transformation of plastids does
      not cause deleterious effects, however it is a complicated procedures. Results:
      We have developed another TYLCV-based vector (SE100) and show that yet another
      bacterial operon (the phaCAB operon) when driven by SE100 is also expressed in
      plants. We employed the combination of SE100 and the phaCAB operon to drive the
      operon to the plastids and produce in plants a biodegradable plastic
      [polyhydroxybutyrate (PHB)].Here we indicate that the bacterial operon (phaCAB),
      when driven by the newly developed universal plant vector SE100 is directed to
      chloroplasts and produces in plants PHB, a leading PHA. The PHB-producing plants
      circumvent the need for complicated technical procedures. Conclusion: The viral
      vector system SE100 facilitated the production of the bio-plastic poly-3
      hydroxybutyrate. This was achieved by using the full pha-CAB operon indicating
      that TYLCV based system can transcribe and translate genes from bacterial operons
      controlled by a single cis element. Our data hints to the participation of the
      chloroplasts in these processes.

PMID- 29201141
TI  - Valorization of pyrolysis water: a biorefinery side stream, for 1,2-propanediol
      production with engineered Corynebacterium glutamicum.
AB  - Background: A future bioeconomy relies on the efficient use of renewable
      resources for energy and material product supply. In this context, biorefineries
      have been developed and play a key role in converting lignocellulosic residues.
      Although a holistic use of the biomass feed is desired, side streams evoke in
      current biorefinery approaches. To ensure profitability, efficiency, and
      sustainability of the overall conversion process, a meaningful valorization of
      these materials is needed. Here, a so far unexploited side stream derived from
      fast pyrolysis of wheat straw-pyrolysis water-was used for production of 1,2
      propanediol in microbial fermentation with engineered Corynebacterium glutamicum.
      Results: A protocol for pretreatment of pyrolysis water was established and
      enabled growth on its major constituents, acetate and acetol, with rates up to
      0.36 +/- 0.04 h-1. To convert acetol to 1,2-propanediol, the plasmid pJULgldA
      expressing the glycerol dehydrogenase from Escherichia coli was introduced into
      C. glutamicum. 1,2-propanediol was formed in a growth-coupled biotransformation
      and production was further increased by construction of C. glutamicum Deltapqo
      DeltaaceE DeltaldhA Deltamdh pJULgldA. In a two-phase aerobic/microaerobic fed
      batch process with pyrolysis water as substrate, this strain produced 18.3 +/-
      1.2 mM 1,2-propanediol with a yield of 0.96 +/- 0.05 mol 1,2-propanediol per mol
      acetol and showed an overall volumetric productivity of 1.4 +/- 0.1 mmol 1,2
      propanediol L-1 h-1. Conclusions: This study implements microbial fermentation
      into a biorefinery based on pyrolytic liquefaction of lignocellulosic biomass and
      accesses a novel value chain by valorizing the side stream pyrolysis water for
      1,2-PDO production with engineered C. glutamicum. The established bioprocess
      operated at maximal product yield and accomplished the so far highest overall
      volumetric productivity for microbial 1,2-PDO production with an engineered
      producer strain. Besides, the results highlight the potential of microbial
      conversion of this biorefinery side stream to other valuable products.

PMID- 29201142
TI  - A novel GH10 xylanase from Penicillium sp. accelerates saccharification of
      alkaline-pretreated bagasse by an enzyme from recombinant Trichoderma reesei
      expressing Aspergillus beta-glucosidase.
AB  - Background: Trichoderma reesei is considered a candidate fungal enzyme producer
      for the economic saccharification of cellulosic biomass. However, performance of
      the saccharifying enzymes produced by T. reesei is insufficient. Therefore, many
      attempts have been made to improve its performance by heterologous protein
      expression. In this study, to increase the conversion efficiency of alkaline
      pretreated bagasse to sugars, we conducted screening of biomass-degrading enzymes
      that showed synergistic effects with enzyme preparations produced by recombinant
      T. reesei. Results: Penicillium sp. strain KSM-F532 produced the most effective
      enzyme to promote the saccharification of alkaline-pretreated bagasse. Biomass
      degrading enzymes from strain KSM-F532 were fractionated and analyzed, and a
      xylanase, named PspXyn10, was identified. The amino acid sequence of PspXyn10 was
      determined by cDNA analysis: the enzyme shows a modular structure consisting of
      glycoside hydrolase family 10 (GH10) and carbohydrate-binding module family 1
      (CBM1) domains. Purified PspXyn10 was prepared from the supernatant of a
      recombinant T. reesei strain. The molecular weight of PspXyn10 was estimated to
      be 55 kDa, and its optimal temperature and pH for xylanase activity were 75 
      degrees C and pH 4.5, respectively. More than 80% of the xylanase activity was
      maintained at 65  degrees C for 10 min. With beechwood xylan as the substrate,
      the enzyme had a Km of 2.2 mg/mL and a Vmax of 332 MUmol/min/mg.
      PspXyn10DeltaCBM, which lacked the CBM1 domain, was prepared by limited
      proteolysis. PspXyn10DeltaCBM showed increased activity against soluble xylan,
      but decreased saccharification efficiency of alkaline-pretreated bagasse. This
      result indicated that the CBM1 domain of PspXyn10 contributes to the enhancement
      of the saccharification efficiency of alkaline-pretreated bagasse. A recombinant
      T. reesei strain, named X2PX10, was constructed from strain X3AB1. X3AB1 is an
      Aspergillus aculeatus beta-glucosidase-expressing T. reesei PC-3-7. X2PX10 also
      expressed PspXyn10 under the control of the xyn2 promoter. An enzyme preparation
      from X2PX10 showed almost the same saccharification efficiency of alkaline
      pretreated bagasse at half the enzyme dosage as that used for an enzyme
      preparation from X3AB1. Conclusions: Our results suggest that PspXyn10 promotes
      the saccharification of alkaline-pretreated bagasse more efficiently than TrXyn3,
      a GH10 family xylanase from T. reesei, and that the PspXyn10-expressing strain is
      suitable for enzyme production for biomass saccharification.

PMID- 29201143
TI  - Transcriptomic profiling and genetic analyses reveal novel key regulators of
      cellulase and xylanase gene expression in Penicillium oxalicum.
AB  - Background: The transition to a more environmentally friendly economy has
      prompted studies of modern biorefineries, including the utilization of low-value
      lignocellulose. The major challenge facing the widespread application of
      biorefineries is the high cost of enzymes that can efficiently hydrolyze
      recalcitrant cellulose to sugars. Penicillium oxalicum produces large amounts of
      plant-cell-wall-degrading enzymes, but their production is tightly controlled by
      complex regulatory networks, resulting in low yields of the native enzymes.
      Regulatory genes have been the targets of genetic engineering to improve enzyme
      production in microorganisms. In this study, we used transcriptomic profiling and
      genetic analyses to screen for and identify novel key regulators of cellulase and
      xylanase gene expression in P. oxalicum. Results: A comparative analysis of the
      transcriptomes of P. oxalicum HP7-1 on different carbon sources, including
      glucose, wheat bran, and wheat bran plus Avicel, identified 40 candidate genes
      regulating the expression of cellulolytic enzyme genes. Deletion mutants of 31
      candidate genes were constructed in P. oxalicum ?PoxKu70 and 11 resultant mutants
      showed significant changes in their filter-paper cellulase production compared
      with the parental strain ?PoxKu70. Among these 11 mutants, DeltaPoxCxrA,
      DeltaPoxCxrB, and DeltaPoxNsdD showed the most significant reduction in the
      enzyme production (96.8, 75.9, and 58.5%, respectively). Ten of these 11 genes
      are here reported to be involved in cellulase production for the first time.
      Further tests revealed that DeltaPoxCxrA, DeltaPoxCxrB, and DeltaPoxNsdD
      displayed significantly reduced xylanase production, whereas DeltaPoxCxrA
      produced negligible xylanase. Interestingly, DeltaPoxCxrB and DeltaPoxNsdD showed
      significantly increased beta-glucosidase production. Real-time quantitative
      reverse transcription-PCR and an electrophoretic mobility shift assay (EMSA)
      showed that PoxCxrA, PoxCxrB, and PoxNsdD regulate the expression of one another,
      but the mode of regulation changes dynamically during the growth of fungal cells
      in the presence of cellulose. EMSA showed that PoxCxrA, PoxCxrB, and PoxNsdD
      directly bind the putative promoters of major cellulase and xylanase genes.
      Conclusions: We have detected and identified three key new regulatory genes,
      PoxCxrA, PoxCxrB, and PoxNsdD, that directly and indirectly regulate the
      expression of cellulase and xylanase genes in P. oxalicum. This study provides
      novel insights into the regulatory mechanisms of fungal cellulase and xylanase
      gene expression.

PMID- 29201144
TI  - Length of stay, costs, and complications in lumbar disc herniation surgery by
      standard PLIF versus a new dynamic interspinous stabilization technique.
AB  - Background: The number of lumbar spine surgeries has been increasing during the
      last 20 years, which also leads to an increase in hospital costs and
      complications related to surgery. Therefore, there is a greater concern about the
      costs and safety of the techniques and implants used. Methods: Patients (aged
      from 18 to 50 years) presenting with lumbago /sciatica (ICD-10-CM M54.3, M54.4)
      due to lumbar disc herniation lasting more than 12 weeks, were included. Patients
      with disc herniation larger than size-2 or size-3 according to the MSU
      Classification were eligible for participation. Intervention was divided in two
      groups. In Group 1, patients underwent microdiscectomy and Interspinous Dynamic
      Stabilization System (IDSS). Meanwhile, in Group 2, patients received discectomy
      and posterior lumbar interbody fusion (PLIF). The primary outcome measure was the
      length of stay and costs during hospital admission. We also evaluated several
      other outcome parameters, including 90- day readmission rate, 90-day complication
      rate, and re-operations rate. The study was an observational prospective cohort
      study carried out from January 2015 to August 2016 in which two surgical
      techniques were compared. Our hypothesis was that a less aggressive procedure,
      such as discectomy and DSS, will decrease the length of stay and costs, and that
      it will also reduce the rate of complications with respect to PLIF. Results: A
      total of 67 patients (mean age 39.8 +/- 8.4 years) were included. Patients in the
      PLIF group had a length of stay increase of 109% (4.52 +/- 1.76 days vs 2.16 +/-
      1.18 days p < 0.001) and an in-hospital cost increase of 71% (1821.97 +/- 460.41?
      vs. 1066.20 +/- 284.34? p < 0.001). The reduction of one day of stay is
      equivalent to a reduction of total in-hospital costs of 12.5%. Patients in the
      IDSS cohort had no significant differences regarding PLIF cohort in the 90-day
      readmission rate (12.9% vs 11.1% ? p > 0.999, respectively), 90-day re-operation
      rate (12.9% vs 11.1% ? p > 0.999) and 90-day complication rates (35.5% vs 52.8% ?
      p > 0.156). Dural tear and urinary tract infection rates were higher in the PLIF
      cohort (13.9% vs 3.2%. p = 0.205 and 11.1% vs 0% p = 0.118, respectively).
      Implant related complications were the most frequent in both IDSS and PLIF groups
      (32.3% vs 38.9% p = 0.572). Conclusions: Patients who underwent IDSS had a
      significant decrease of the length of stay and costs in relation to PLIF group.
      No significant differences were found in 90-day readmission and reintervention
      rates for both groups. Although differences were not significant, dural tear and
      urinary tract infection rates were lower in the interspinous group. IDSS or PLIF
      after discectomy, did not protect against subsequent 90-day re-operation or
      readmission compared to discectomy alone.

PMID- 29201145
TI  - OCDD: an obesity and co-morbid disease database.
AB  - Background: Obesity is a medical condition that is known for increased body mass
      index (BMI). It is also associated with chronic low level inflammation. Obesity
      disrupts the immune-metabolic homeostasis by changing the secretion of
      adipocytes. This affects the end-organs, and gives rise to several diseases
      including type 2 diabetes, asthma, non-alcoholic fatty liver diseases and
      cancers. These diseases are known as co-morbid diseases. Several studies have
      explored the underlying molecular mechanisms of developing obesity associated
      comorbid diseases. To understand the development and progression of diseases
      associated with obesity, we need a detailed scenario of gene interactions and the
      distribution of the responsible genes in human system. Results: Obesity and Co
      morbid Disease Database (OCDD) is designed for relating obesity and its co-morbid
      diseases using literature mining, and computational and systems biology
      approaches. OCDD is aimed to investigate the genes associated with comorbidity.
      Several existing databases have been used to extract molecular interactions and
      functional annotations of each gene. The degree of co-morbid associations has
      been measured and made available to the users. The database is available at
      http://www.isical.ac.in/~systemsbiology/OCDD/home.php. Conclusions: The main
      objective of the database is to derive the relations among the genes that are
      involved in both obesity and its co-morbid diseases. Functional annotation of
      common genes, gene interaction networks and key driver analyses have made the
      database a valuable and comprehensive resource for investigating the causal links
      between obesity and co-morbid diseases.

PMID- 29201146
TI  - Time to revise our dialogue: how flat is the paediatric flatfoot?
AB  - A recent systematic review of measures of foot development used the medial
      longitudinal arch profile as its primary indicator of development. A comparative
      analysis of existing studies was undertaken. This work confirmed changes with
      arch profile were age-dependent, although the age at which foot development
      ceased remains unknown. This work also highlighted the abundance of clinical
      measures used in existing research and outlined the challenges with drawing
      consensus from available data. There is a clear need to move this debate forward
      and, to do so, it is essential that scientific and clinical communities unite. It
      is time to abandon ill-defined measures of foot position, look beyond the medial
      longitudinal arch as a sole parameter of foot development and re-focus our
      perspective(s) on the paediatric foot in order to make advances with clinical
      practice and research.

PMID- 29200941
TI  - Measurements of the production cross section of a [Formula: see text] boson in
      association with jets in pp collisions at [Formula: see text] TeV with the ATLAS
      detector.
AB  - Measurements of the production cross section of a [Formula: see text] boson in
      association with jets in proton-proton collisions at [Formula: see text] TeV are
      presented, using data corresponding to an integrated luminosity of 3.16
      fb[Formula: see text] collected by the ATLAS experiment at the CERN Large Hadron
      Collider in 2015. Inclusive and differential cross sections are measured for
      events containing a [Formula: see text] boson decaying to electrons or muons and
      produced in association with up to seven jets with [Formula: see text] GeV and
      [Formula: see text]. Predictions from different Monte Carlo generators based on
      leading-order and next-to-leading-order matrix elements for up to two additional
      partons interfaced with parton shower and fixed-order predictions at next-to
      leading order and next-to-next-to-leading order are compared with the measured
      cross sections. Good agreement within the uncertainties is observed for most of
      the modelled quantities, in particular with the generators which use next-to
      leading-order matrix elements and the more recent next-to-next-to-leading-order
      fixed-order predictions.

PMID- 29201147
TI  - Evidence for current recommendations concerning the management of foot health for
      people with chronic long-term conditions: a systematic review.
AB  - Background: Research focusing on management of foot health has become more
      evident over the past decade, especially related to chronic conditions such as
      diabetes. The level of methodological rigour across this body of work however is
      varied and outputs do not appear to have been developed or translated into
      clinical practice. The aim of this systematic review was to assess the latest
      guidelines, standards of care and current recommendations relative to people with
      chronic conditions to ascertain the level of supporting evidence concerning the
      management of foot health. Methods: A systematic search of electronic databases
      (Medline, Embase, Cinahl, Web of Science, SCOPUS and The Cochrane Library) for
      literature on recommendations for foot health management for people with chronic
      conditions was performed between 2000 and 2016 using predefined criteria. Data
      from the included publications was synthesised via template analysis, employing a
      thematic organisation and structure. The methodological quality of all included
      publications was appraised using the Appraisal for Research and Evaluation (AGREE
      II) instrument. A more in-depth analysis was carried out that specifically
      considered the levels of evidence that underpinned the strength of their
      recommendations concerning management of foot health. Results: The data collected
      revealed 166 publications in which the majority (102) were guidelines, standards
      of care or recommendations related to the treatment and management of diabetes.
      We noted a trend towards a systematic year on year increase in guidelines
      standards of care or recommendations related to the treatment and management of
      long term conditions other than diabetes over the past decade. The most common
      recommendation is for preventive care or assessments (e.g. vascular tests),
      followed by clinical interventions such as foot orthoses, foot ulcer care and
      foot health education. Methodological quality was spread across the range of
      AGREE II scores with 62 publications falling into the category of high quality
      (scores 6-7). The number of publications providing a recommendation in the
      context of a narrative but without an indication of the strength or quality of
      the underlying evidence was high (79 out of 166). Conclusions: It is clear that
      evidence needs to be accelerated and in place to support the future of the
      Podiatry workforce. Whilst high level evidence for podiatry is currently low in
      quantity, the methodological quality is growing. Where levels of evidence have
      been given in in high quality guidelines, standards of care or recommendations,
      they also tend to be strong-moderate quality such that further strategically
      prioritised research, if performed, is likely to have an important impact in the
      field.

PMID- 29201149
TI  - Complete genome sequence of the Vibrio vulnificus strain VV2014DJH, a human
      pathogenic bacterium isolated from a death case in China.
AB  - Background: Vibrio vulnificus, an opportunistic pathogen, is the causative agent
      of life-threatening septicemia and severe wound infections. However, the
      pathogenicity and virulence factors of V. vulnificus are not fully understood.
      Here we report the complete genome sequence of V. vulnificus VV2014DJH, which was
      isolated from a death case. Results: The genome of the V. vulnificus VV2014DJH
      contains two circular chromosomes with a mean G+C content of 46.8%, but does not
      consists of any plasmids. The chromosome I and chromosome II consist of 3,303,590
      and 1,770,972 bp, respectively. In addition, the genome consists of 4617 protein
      coding genes, 172 RNA genes and type I, II and III secretion systems were
      predicted. Conclusions: In this study, the genomic information of the V.
      vulnificus VV2014DJH has been described. The information would contribute to the
      increasing scope and depth of Vibrio genome database, and provide insights into
      the pathogenicity and virulence factors of V. vulnificus.

PMID- 29201148
TI  - Whole genome sequencing-based detection of antimicrobial resistance and virulence
      in non-typhoidal Salmonella enterica isolated from wildlife.
AB  - The aim of this study was to generate a reference set of Salmonella enterica
      genomes isolated from wildlife from the United States and to determine the
      antimicrobial resistance and virulence gene profile of the isolates from the
      genome sequence data. We sequenced the whole genomes of 103 Salmonella isolates
      sampled between 1988 and 2003 from wildlife and exotic pet cases that were
      submitted to the Oklahoma Animal Disease Diagnostic Laboratory, Stillwater,
      Oklahoma. Among 103 isolates, 50.48% were from wild birds, 0.9% was from fish,
      24.27% each were from reptiles and mammals. 50.48% isolates showed resistance to
      at least one antibiotic. Resistance against the aminoglycoside streptomycin was
      most common while 9 isolates were found to be multi-drug resistant having
      resistance against more than three antibiotics. Determination of virulence gene
      profile revealed that the genes belonging to csg operons, the fim genes that
      encode for type 1 fimbriae and the genes belonging to type III secretion system
      were predominant among the isolates. The universal presence of fimbrial genes and
      the genes encoded by pathogenicity islands 1-2 among the isolates we report here
      indicates that these isolates could potentially cause disease in humans.
      Therefore, the genomes we report here could be a valuable reference point for
      future traceback investigations when wildlife is considered to be the potential
      source of human Salmonellosis.

PMID- 29201154
TI  - Lymphatic system and gut microbiota affect immunopathology of neuroinflammatory
      diseases, including multiple sclerosis, neuromyelitis optica and Alzheimer's
      disease.
AB  - Microbial infections lead to neurological damages either by direct infection in
      the nervous tissues or by uncontrolled immune responses (immunopathology). For
      example, in Zika virus infection, microcephaly can be caused by the former, i.e.,
      direct viral infection in the brain, while Guillain-Barre syndrome (GBS) seems to
      be antibody-mediated immunopathology. Although a variety of factors affect
      immunopathology, two essential systems maintaining whole-body homeostasis had
      long been neglected: 1) the lymphatic system and 2) microbiota. Only recently,
      the role of the lymphatic system in immunopathology is beginning to be clarified.
      During infection, increased lymphatic flow limits edema and prevent tissue
      dendritic cell retention, while lymphostasis can lead to chronic inflammation.
      The role of gut microbiota, particularly bacterial community, in immunopathology
      has also been clarified recently; "bad bacteria" are proposed to exacerbate any
      immunopathology. For example, Helicobacter pylori is associated with not only
      gastritis but also extra-intestinal diseases, including neuromyelitis optica
      (NMO) and Alzheimer's disease. However, H. pylori and another bad bacterium
      Clostridium perfringens type A have been proposed to be protective against
      multiple sclerosis (MS). The above discrepancy on the roles of microbiota can be
      attributed to several conflicting factors, such as oversimplification,
      methodology, and taxonomy, which are summarized as "10 pitfalls of microbiota
      studies."

PMID- 29201151
TI  - Complete genome sequences of Clostridium perfringens Del1 strain isolated from
      chickens affected by necrotic enteritis.
AB  - Background: Clostridium perfringens is ubiquitous in nature. It is a normal
      inhabitant in the intestinal tract of animals and humans. As the primary
      etiological agent of gas gangrene, necrosis and bacteremia, C. perfringens causes
      food poisoning, necrotic enteritis (NE), and even death. Epidemiology research
      has indicated that the increasing incidence of NE in poultry is associated with
      the withdrawal of in-feed antibiotic growth promoters in poultry production in
      response to government regulations. The recent omics studies have indicated that
      bacterial virulence is typically linked to highly efficient conjugative transfer
      of toxins, or plasmids carrying antibiotic-resistance traits. Currently, there is
      limited information on understanding of host-pathogen interaction in NE caused by
      virulent strains of C. perfringens. Elucidating such pathogenesis has practical
      impacts on fighting infectious diseases through adopting strategies of
      prophylactic or therapeutic interventions. In this report, we sequenced and
      analyzed the genome of C. perfringens Del1 strain using the hybrid of PacBio and
      Illumina sequencing technologies. Results: Sequence analysis indicated that Del1
      strain comprised a single circular chromosome with a complete 3,559,163 bp and 4
      plasmids: pDel1_1 (82,596 bp), pDel1_2 (69,827 bp), pDel1_3 (49,582 bp), and
      pDel1_4 (49,728 bp). The genome had 3361 predicted coding DNA sequences, harbored
      numerous genes for pathogenesis and virulence factors, including 6 for antibiotic
      and antimicrobial resistance, and 3 phage-encoded genes. Phylogenetic analysis
      revealed that Del1 strain had similar genome and plasmid sequences to the CP4
      strain. Conclusion: Complete chromosomal and plasmid sequences of Del1 strain are
      presented in this report. Since Del1 was isolated from a field disease outbreak,
      this strain is a good source to identify virulent genes that cause many damaging
      effects of Clostridial infections in chicken gut. Genome sequencing of the
      chicken pathogenic isolates from commercial farms provides valuable insights into
      the molecular pathogenesis of C. perfringens as a gastrointestinal pathogen in
      food animals. The detailed information on gene sequencing of this important field
      strain will benefit the development of novel vaccines specific for C. perfringens
      induced NE in chickens.

PMID- 29201150
TI  - Differences in the gut microbiota of dogs (Canis lupus familiaris) fed a natural
      diet or a commercial feed revealed by the Illumina MiSeq platform.
AB  - Background: Recent advances in next-generation sequencing technologies have
      enabled comprehensive analysis of the gut microbiota, which is closely linked to
      the health of the host. Consequently, several studies have explored the factors
      affecting gut microbiota composition. In recent years, increasing number of dog
      owners are feeding their pets a natural diet i.e., one consisting of bones, raw
      meat (such as chicken and beef), and vegetables, instead of commercial feed.
      However, the effect of these diets on the microbiota of dogs (Canis lupus
      familiaris) is unclear. Methods and results: Six dogs fed a natural diet and five
      dogs fed a commercial feed were selected; dog fecal metagenomic DNA samples were
      analyzed using the Illumina MiSeq platform. Pronounced differences in alpha and
      beta diversities, and taxonomic composition of the core gut microbiota were
      observed between the two groups. According to alpha diversity, the number of
      operational taxonomic units, the richness estimates, and diversity indices of
      microbiota were significantly higher (p < 0.05) in the natural diet group than in
      the commercial feed group. Based on beta diversity, most samples clustered
      together according to the diet type (p = 0.004). Additionally, the core
      microbiota between the two groups was different at the phylum, family, and
      species levels. Marked differences in the taxonomic composition of the core
      microbiota of the two groups were observed at the species level; Clostridium
      perfringens (p = 0.017) and Fusobacterium varium (p = 0.030) were more abundant
      in the natural diet group. Conclusions: The gut microbiota of dogs is
      significantly influenced by diet type (i.e., natural diet and commercial feed).
      Specifically, dogs fed a natural diet have more diverse and abundant microbial
      composition in the gut microbiota than dogs fed a commercial feed. In addition,
      this study suggests that in dogs fed a natural diet, the potential risk of
      opportunistic infection could be higher, than in dogs fed a commercial feed. The
      type of diet might therefore play a key role in animal health by affecting the
      gut microbiota. This study could be the basis for future gut microbiota research
      in dogs.

PMID- 29201152
TI  - Myocardial injury in diabetic patients with multivessel coronary artery disease
      after revascularization interventions.
AB  - Background: Diabetic patients may be more susceptible to myocardial injury after
      coronary interventions. Thus, the aim of this study was to assess the release of
      cardiac biomarkers, CK-MB and troponin, and the findings of new late gadolinium
      enhancement (LGE) on cardiac magnetic resonance (CMR) in patients with type 2
      diabetes mellitus after elective revascularization procedures for multivessel
      coronary artery disease (CAD). Methods: Patients with multivessel CAD and
      preserved systolic ventricular function underwent either elective percutaneous
      coronary intervention (PCI), off-pump or on-pump bypass surgery (CABG). Troponin
      and CK-MB were systematically collected at baseline, 6, 12, 24, 36, 48 and 72 h
      after the procedures. CMR with LGE was performed before and after the
      interventions. Patients were stratified according to diabetes status at study
      entry. Biomarkers and CMR results were compared between diabetic and nondiabetics
      patients. Analyses of correlation were also performed among glycemic and glycated
      hemoglobin (A1c) levels and troponin and CK-MB peak levels. Patients were also
      stratified into tertiles of fasting glycemia and A1c levels and were compared in
      terms of periprocedural myocardial infarction (PMI) on CMR. Results: Ninety
      (44.5%) of the 202 patients had diabetes mellitus at study entry. After
      interventions, median peak troponin was 2.18 (0.47, 5.14) and 2.24 (0.69, 5.42)
      ng/mL (P = 0.81), and median peak CK-MB was 14.1 (6.8, 31.7) and 14.0 (4.2, 29.8)
      ng/mL (P = 0.43), in diabetic and nondiabetic patients, respectively. The release
      of troponin and CK-MB over time was statistically similar in both groups and in
      the three treatments, besides PCI. New LGE on CMR indicated that new myocardial
      fibrosis was present in 18.9 and 17.3% (P = 0.91), and myocardial edema in 15.5
      and 22.9% (P = 0.39) in diabetic and nondiabetic patients, respectively. The
      incidence of PMI in the glycemia tertiles was 17.9% versus 19.3% versus 18.7% (P
      = 0.98), and in the A1c tertiles was 19.1% versus 13.3% versus 22.2% (P = 0.88).
      Conclusions: In this study, diabetes mellitus did not add risk of myocardial
      injury after revascularization interventions in patients with multivessel
      coronary artery disease. Trial Registration Name of Registry: Evaluation of
      cardiac biomarker elevation after percutaneous coronary intervention or coronary
      artery bypass graft; URL: http://www.controlled-trials.com.ISRCTN09454308.

PMID- 29201153
TI  - Poor glycaemic control is associated with reduced exercise performance and oxygen
      economy during cardio-pulmonary exercise testing in people with type 1 diabetes.
AB  - Background: To explore the impact of glycaemic control (HbA1c) on functional
      capacity during cardio-pulmonary exercise testing in people with type 1 diabetes.
      Methods: Sixty-four individuals with type 1 diabetes (age: 34 +/- 8 years; 13
      females, HbA1c: 7.8 +/- 1% (62 +/- 13 mmol/mol), duration of diabetes: 17 +/- 9
      years) performed a cardio-pulmonary cycle ergometer exercise test until
      volitional exhaustion. Stepwise linear regression was used to explore
      relationships between HbA1c and cardio-respiratory data with p <= 0.05.
      Furthermore, participants were divided into quartiles based on HbA1c levels and
      cardio-respiratory data were analysed by one-way ANOVA. Multiple regression
      analysis was performed to explore the relationships between changes in time to
      exhaustion and cardio-respiratory data. Data were adjusted for confounder.
      Results: HbA1c was related to time to exhaustion and oxygen consumption at the
      power output elicited at the sub-maximal threshold of the heart rate turn point
      (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to
      exhaustion between QI vs. QIV and at oxygen consumption at the power output
      elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p <
      0.05). Changes in oxygen uptake, power output and in oxygen consumption at the
      power output elicited at the heart rate turn point and at maximum power output
      explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p <
      0.01). Conclusions: Poor glycaemic control is related to less economical use of
      oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio
      pulmonary exercise testing. However, exercise training could have the same
      potential to counteract the influence of poor glycaemic control on functional
      capacity. Trial registration NCT01704417. Date of registration: October 11, 2012.

PMID- 29201157
TI  - Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different
      anatomical regions of the human brain.
AB  - Background: Recent reports indicate that retrotransposons - a type of mobile DNA 
      can contribute to neuronal genetic diversity in mammals. Retrotransposons are
      genetic elements that mobilize via an RNA intermediate by a "copy-and-paste"
      mechanism termed retrotransposition. Long Interspersed Element-1 (LINE-1 or L1)
      is the only active autonomous retrotransposon in humans and its activity is
      responsible for ~ 30% of genomic mass. Historically, L1 retrotransposition was
      thought to be restricted to the germline; however, new data indicate L1 s are
      active in somatic tissue with certain regions of the brain being highly
      permissive. The functional implications of L1 insertional activity in the brain
      and how host cells regulate it are incomplete. While deep sequencing and qPCR
      analysis have shown that L1 copy number is much higher in certain parts of the
      human brain, direct in vivo studies regarding detection of L1-encoded proteins is
      lacking due to ineffective reagents. Results: Using a polyclonal antibody we
      generated against the RNA-binding (RRM) domain of L1 ORF1p, we observe widespread
      ORF1p expression in post-mortem human brain samples including the hippocampus
      which has known elevated rates of retrotransposition. In addition, we find that
      two brains from different individuals of different ages display very different
      expression of ORF1p, especially in the frontal cortex. Conclusions: We
      hypothesize that discordance of ORF1p expression in parts of the brain reported
      to display elevated levels of retrotransposition may suggest the existence of
      factors mediating post-translational regulation of L1 activity in the human
      brain. Furthermore, this antibody reagent will be useful as a complementary means
      to confirm findings related to retrotransposon biology and activity in the brain
      and other tissues in vivo.

PMID- 29201158
TI  - Biomonitoring method for the analysis of chromium and cobalt in human whole blood
      using inductively coupled plasma - kinetic energy discrimination - mass
      spectrometry (ICP-KED-MS).
AB  - The Centers for Disease Control and Prevention developed a biomonitoring method
      to rapidly and accurately quantify chromium and cobalt in human whole blood by
      ICP-MS. Many metal-on-metal hip implants which contain significant amounts of
      chromium and cobalt are susceptible to metal degradation. This method is used to
      gather population data about chromium and cobalt exposure of the U.S. population
      that does not include people that have metal-on-metal hip implants so that
      reference value can be established for a baseline level in blood. We evaluated
      parameters such as; helium gas flow rate, choice and composition of the diluent
      solution for sample preparation, and sample rinse time to determine the optimal
      conditions for analysis. The limits of detection for chromium and cobalt in blood
      were determined to be 0.41 and 0.06 MUg/L, respectively. Method precision,
      accuracy, and recovery for this method were determined using quality control
      material created in-house and historical proficiency testing samples. We
      conducted experiments to determine if quantitative changes in the method
      parameters affect the results obtained by changing four parameters while
      analyzing human whole blood spiked with National Institute of Standard and
      Technology traceable materials: the dilution factor used during sample
      preparation, sample rinse time, diluent composition, and kinetic energy
      discrimination gas flow rate. The results at the increased and decreased levels
      for each parameter were statistically compared to the results obtained at the
      optimized parameters. We assessed the degree of reproducibility obtained under a
      variety of conditions and evaluated the method's robustness by analyzing the same
      set of proficiency testing samples by different analysts, on different
      instruments, with different reagents, and on different days. The short-term
      stability of chromium and cobalt in human blood samples stored at room
      temperature was monitored over a time period of 64 hours by diluting and
      analyzing samples at different time intervals. The stability of chromium and
      cobalt post-dilution was also evaluated over a period of 48 hours and at two
      storage temperatures (room temperature and refrigerated at 4 degrees C). The
      results obtained during the stability studies showed that chromium and cobalt are
      stable in human blood for a period of 64 hours.

PMID- 29201155
TI  - Critical issues and current challenges in osteoporosis and fracture prevention.
      An overview of unmet needs.
AB  - Osteoporosis is a silent disease with increasing prevalence due to the global
      ageing population. Decreased bone strength and bone quality is the hallmark of
      osteoporosis which leads to an increased risk of fragility fractures in elderly.
      It has been estimated that approximately ~50% of women will suffer during their
      lifetime from an osteoporotic fracture. This must be considered as a major health
      concern, as it has previously been established that fragility fracture has been
      associated with decreased quality of life due to increased disability, more
      frequent hospital admission and most importantly, osteoporotic fractures have
      been related to an augmented mortality risk. Anti-osteoporotic drugs are
      available for improving bone quality. Although there is access to these
      therapeutic options, there remain multiple unmet needs in the field of
      osteoporosis and fracture care, for example, the primary prevention of
      osteoporosis in young individuals (to reach a high peak bone mass), the
      optimization of the use of imaging techniques [dual-energy X-ray absorptiometry
      (DXA), vertebral fracture assessment (VFA) and new techniques measuring bone
      quality], the use of nonmedical treatment options and surgical techniques of
      fracture healing. In this review, we will discuss topics that play a role in the
      occurrence and prevention of fractures, and we give an overview of and insight
      into the critical issues and challenges around osteoporosis and fracture
      prevention.

PMID- 29201156
TI  - Evidence-based management of Raynaud's phenomenon.
AB  - Raynaud's phenomenon (RP) is relevant to the rheumatologist because it may
      signify an underlying connective tissue disease and also because it can be very
      challenging to treat, especially when it has progressed to digital ulceration or
      critical ischaemia. This review article discusses diagnosis (does this patient
      have an underlying connective tissue disease?), including the role for nailfold
      capillaroscopy, and treatment. Management of 'uncomplicated' RP is first
      described and then treatment of RP complicated by progression to digital
      ulceration or critical ischaemia, highlighting recent advances (including
      phosphodiesterase type 5 inhibition, and endothelin 1 receptor antagonism) and
      the evidence base underpinning these. Possible future therapies are briefly
      discussed.

PMID- 29201159
TI  - Cardiovascular risks in chronic kidney disease pediatric patients.
AB  - One of the common factors for the premature death in children is advanced chronic
      kidney disease (CKD). Most often cardiovascular disease (CVD) is the reason for
      mortality. The cardiovascular (CV) morbidity starts early in the disease process
      and renal transplanted children (CKD-T) are also at risk. The present review is
      focused on the current views of the cardiovascular risks during CKD in pediatric
      patients. Variable data sources for the latest literature collection were
      explored which mainly included PubMed and Google Scholar. The most important risk
      factors for subclinical CVD were a young age, elevated BMI and systolic blood
      pressure z-scores as well as a low GFR and present albuminuria. Increasing blood
      pressure and BMI over follow-up were also important cardiac risk factors
      longitudinally. The present review concludes that altered cardiac function and
      remodeling are a concurrent part of the CKD process, start early in the disease
      development, and persist after renal transplantation. The findings suggest that
      children with CKD or CKD-T are at high risk for future CVD where younger patients
      with elevated BMI and slightly increased blood pressures, as well as present
      albuminuria, are those at greatest risk, thus indicating targets for future
      interventions.

PMID- 29201161
TI  - Identification of key genes influenced by fixation stability in early fracture
      hematoma and elucidation of their roles in fracture healing.
AB  - The present study aimed to identify the key genes influenced by fixation
      stability in early fracture hematoma and to elucidate their roles in fracture
      healing. The GSE53256 gene expression profile, including six fracture hematoma
      tissues, was downloaded from the Gene Expression Omnibus database. The
      differentially expressed genes (DEGs) in the fracture hematoma tissues from old
      rats with rigid fixation compared with semi-rigid fixation were identified using
      the limma package. Furthermore, Gene Ontology (GO) enrichment analysis for DEGs
      was performed using BiNGO, and a protein-protein interaction (PPI) network was
      constructed based on the Search Tool for the Retrieval of Interacting Genes
      database. A total of 265 DEGs (158 upregulated and 107 downregulated) in the
      fracture hematoma tissues were screened out. Additionally, the overrepresented GO
      terms were mainly associated with the extracellular region, positive regulation
      of locomotion and response to external stimulus. Transforming growth factor, beta
      1 (Tgfbeta1), chemokine (C-X-C motif) ligand 12 (Cxcl12), matrix metallopeptidase
      9 (mmp9) and serpin peptidase inhibitor, clade E, member 1 (serpine1) had higher
      degrees and were hub nodes in the PPI network. In conclusion, fixation stability
      may influence the fracture healing process, and important DEGs, including Cxcl12,
      mmp9, Tgfbeta1 and serpine1, may be important in this process.

PMID- 29201160
TI  - EGFR and Cortactin: Markers for potential double target therapy in oral squamous
      cell carcinoma.
AB  - Survival periods of patients following surgical therapy of oral squamous cell
      carcinoma (OSCC) have previously been demonstrated to decrease over recent
      decades. Epidermal growth factor receptor (EGFR) and Cortactin are molecular
      markers that are important in tumour progression and development, and interact
      within the EGF pathway. Although EGFR antibody therapy exists, sufficient efforts
      for increased survival are still lacking due to the present limited response
      rates. The aim of the present study was to examine the association between EGFR
      and Cortactin expression on survival rates of OSCC patients and to determine
      whether EGFR and Cortactin expression levels are associated with advanced tumor
      sizes and lymphnode-metastases. In total, 222 OSCC patients were included in the
      study. EGFR and Cortactin expression in tumor tissue was evaluated by
      immunohistochemistry. Cox regression was used for survival analysis. Categories
      were tested for associations by using cross tabs (Chi-square test). Groups were
      compared by the non-parametric Mann Whitney U-test. Probabilities of less than
      0.05 were considered significant and significant expression of Cortactin was
      observed in Advanced Union Internationale Contre le Cancer stage (P=0.032),
      including advanced tumour stage (P=0.021) and lymph node metastasis (P=0.049).
      High Cortactin expression was significantly associated with poorer survival rates
      (P=0.037). Further Cortactin expression was not associated with extracapsular
      spread, however EGFR exhibited a significant association (P=0.034). Neither EGFR
      nor Cortactin expression was correlated to grading. EGFR and Cortactin co
      expression was demonstrated to be significantly associated with poorer survival
      rates in OSCC patients, suggesting that identification of predictive biomarkers
      for adjuvant therapies are of primary concern in OSCC. In particular, efficient
      dual-target therapy may act as an appropriate therapy to improve survival time
      for patients at advanced OSCC tumor stages.

PMID- 29201162
TI  - Effect of tanshinone IIA on oxidative stress and apoptosis in a rat model of
      fatty liver.
AB  - Oxidative stress is a crucial factor associated with fatty liver disease, which
      raises the possibility of using antioxidants to improve liver steatosis.
      Tanshinone IIA (TSIIA) is a traditional Chinese medicine that has been reported
      to have antioxidant effects in vitro. The present study aimed to investigate
      whether TSIIA possesses antioxidant effects in vivo and whether TSIIA was able to
      improve liver steatosis. Hence, the ability of TSIIA to protect rats from liver
      disease was explored, particularly in regard to antioxidant activity. Rats were
      fed a high-lipid diet for 90 days, causing severe liver steatosis, both
      morphologically and biochemically. An increase in reactive oxygen species (ROS)
      in the liver was exhibited in addition to significantly elevated serum lipids and
      malondialdehyde (MDA). Furthermore, hepatocyte apoptosis was measured by Hoechst
      staining, reverse transcription-quantitative polymerase chain reaction and
      western blot analysis and an increase in hepatocyte apoptosis rate was indicated
      in mice on a high-fat diet. Following intraperitoneal injection of TSIIA (10
      mg/kg/day), liver steatosis was significantly inhibited. In rats receiving TSIIA
      treatment, less ROS were indicated in the liver and significantly decreased
      levels of MDA (P<0.05) in serum were exhibited, whereas significantly increased
      activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH
      PX) were observed (P<0.05 and P<0.01, respectively). In addition, the rate of
      hepatocyte apoptosis was significantly decreased in the TSIIA group (P<0.01).
      However, TSIIA elicited no effect on serum lipid profiles. These results suggest
      that TSIIA attenuates oxidative stress by decreasing ROS and MDA production and
      enhancing the activity of T-SOD and GSH-PX, which may contribute to the
      inhibition of apoptosis and amelioration of liver steatosis.

PMID- 29201164
TI  - Electroacupuncture improves acute bowel injury recovery in rat models.
AB  - Electroacupuncture (EA) accelerates intestinal functional recovery in sepsis. The
      present study investigated ghrelin and ghrelin receptor (GSH-R) levels during EA
      in rats with acute bowel injury (ABI). Rats were grouped into four groups: Sham,
      ABI, ABI+EA and ABI+GHRA+EA (n=12 per group). ABI was induced by cecal ligation
      and puncture (CLP). EA on bilateral Zusanli acupoints was performed following
      CLP. GSH-R blocker (GHRA) was used following CLP but prior to EA for ABI+GHRA+EA
      rats. Rats were sacrificed 12 h following CLP. Serum ghrelin, tumor necrosis
      factor-alpha (TNF-alpha) and high mobility group box 1 (HMGB1) levels, as well as
      ghrelin and GSH-R protein expression, water content, pathological changes and
      myeloperoxidase (MPO) and diamine oxidase (DAO) activities in the bowel tissues,
      were measured. ABI rats, compared with the sham rats, had significantly lower
      levels of ghrelin and GSH-R in the serum and bowel tissue, and higher Chiu's
      score (all P<0.05). The ABI+EA rats, compared with the ABI rats, had
      significantly reduced serum TNF-alpha and HMGB1 levels, bowel water content, MPO
      activity and Chiu's score (all P<0.05), and significantly higher serum ghrelin
      (121.2+/-10.7 vs. 86.7+/-6.4 pg/ml), bowel ghrelin (0.12+/-0.02 vs. 0.08+/-0.01),
      GSH-R (0.05+/-0.04 vs. 0.03+/-0.01) and DAO activity (18.74+/-4.18 vs. 13.52+/
      2.33 U/ml; all P<0.05), indicating an improvement of the intestinal mucosal
      barrier. GHRA reversed the protective effects of EA. Therefore, EA improved ABI
      recovery by promoting ghrelin secretion and upregulating GSH-R expression.

PMID- 29201163
TI  - Protein-protein interaction analysis to identify biomarker networks for
      endometriosis.
AB  - The identification of biomarkers and their interaction network involved in the
      processes of endometriosis is a critical step in understanding the underlying
      mechanisms of the disease. The aim of the present study was to construct
      biomarker networks of endometriosis that integrated human protein-protein
      interactions and known disease-causing genes. Endometriosis-associated genes were
      extracted from Genotator and DisGeNet and biomarker network and pathway analyses
      were constructed using atBioNet. Of 100 input genes, 96 were strongly mapped to
      six major modules. The majority of the pathways in the first module were
      associated with the proliferation of cancer cells, the enriched pathways in
      module B were associated with the immune system and infectious diseases, module C
      included pathways related to immune and metastasis, the enriched pathways in
      module D were associated with inflammatory processes, and the majority of the
      pathways in module E were related to replication and repair. The present approach
      identified known and potential biomarkers in endometriosis. The identified
      biomarker networks are highly enriched in biological pathways associated with
      endometriosis, which may provide further insight into the molecular mechanisms
      underlying endometriosis.

PMID- 29201165
TI  - MgCl2 and ZnCl2 promote human umbilical vein endothelial cell migration and
      invasion and stimulate epithelial-mesenchymal transition via the Wnt/beta-catenin
      pathway.
AB  - Previous studies have demonstrated that magnesium and zinc ions promote the
      migration and epithelial-mesenchymal transition (EMT) of cancer/endothelial
      cells. However, the impact of MgCl2 and ZnCl2 on the migration, invasion and EMT
      of human umbilical vein endothelial cells (HUVECs) and the involved mechanisms
      remain unclear. In the present study, HUVECs were incubated with various doses of
      MgCl2 and ZnCl2. The optimum concentrations of MgCl2 and ZnCl2 were selected by
      MTT assay. The migration and invasion capabilities of HUVECs were analyzed by
      Transwell assays. Subsequently, the expression of matrix metalloproteinase (MMP)
      2 and MMP-9 mRNA and protein were determined by reverse transcription
      quantitative polymerase chain reaction, western blotting and ELISA. MMP-2 and MMP
      9 activities were measured by gelatin zymography. Immunofluorescence staining was
      performed to investigate cytoskeletal dynamics using Acti-stainTM 488 Fluorescent
      Phalloidin. Subsequently, the expression of EMT-related markers at the mRNA and
      protein levels and the activation of Wnt/beta-catenin signaling were analyzed.
      The results identified increases in MMP-2 and MMP-9 expression and activity,
      indicating that MgCl2 and ZnCl2 promoted HUVEC migration and invasion. In
      addition, MgCl2 and ZnCl2 treatment induced cytoskeleton remodeling and
      stimulated EMT via activation of the Wnt/beta-catenin signaling pathway,
      characterized by a decrease in E-cadherin and increases in N-cadherin, vimentin
      and Snail. These results suggest that MgCl2 and ZnCl2 may enhance the migration
      and invasion capabilities of HUVECs and promote EMT through the Wnt/beta-catenin
      pathway.

PMID- 29201166
TI  - Small interfering RNA against ERK1/2 attenuates cigarette smoke-induced pulmonary
      vascular remodeling.
AB  - Cigarette smoke may contribute to pulmonary vascular remodeling (PVR), a result
      of the proliferation of pulmonary artery smooth muscle cells (PASMCs), before
      pulmonary hypertension in chronic obstructive pulmonary disease (COPD). Activated
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) are considered to be
      involved the process of PVR. This study investigated the potential role of ERK1/2
      in the proliferation of rat PASMCs (rPASMCs) and cigarette smoke-induced PVR in
      rats. A small interfering RNA (siRNA) against ERK1/2 (ERK1/2-siRNA) was
      synthesized, and it significantly reduced the expression of ERK1/2 and cyclin E1,
      significantly increased the proportion of cells arrested at G0/G1 phase and
      significantly suppressed the proliferation of rPASMCs treated with cigarette
      smoke extract compared with controls (all P<0.05). In rats, ERK1/2-siRNA, which
      was administered intranasally, also inhibited the activation of ERK1/2 and the
      upregulation of cyclin E1, both of which were induced after the rats were exposed
      to cigarette smoke for 3 months. ERK1/2-siRNA also significantly reduced PVR
      (observed by vessel wall thickness and the proportion of fully muscularized
      vessels) in cigarette smoke-exposed rats compared with a negative control siRNA
      (P<0.05). Collectively, these data indicated that ERK1/2-siRNA could attenuate
      PVR in cigarette smoke-exposed rats, and it may have therapeutic value in the
      treatment of COPD.

PMID- 29201168
TI  - Long non-coding RNA linc-ITGB1 promotes cell proliferation and migration in human
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) represents a major endpoint of chronic liver
      diseases and is the third leading cause of cancer-related mortality. Long
      intergenic non-coding RNA-integrin subunit beta1 ITGB1 (linc-ITGB1) is a novel
      long non-coding RNA, which is implicated in the development and progression of
      human tumors. However, its involvement in hepatocarcinogenesis remains to be
      elucidated. In the present study, the specific roles of linc-ITGB1 on cell
      proliferation and metastasis in HCC were investigated. It was initially observed
      that the expression of linc-ITGB1 was significantly elevated in 30 cases of
      clinical HCC tissues relative to their adjacent non-cancerous tissues. Expression
      of linc-ITGB1 was particularly elevated in the highly invasive cell line, HCCLM3.
      Knockdown of linc-ITGB1 in HCCLM3 cells using a specific short hairpin RNA
      decreased cell viability and colony formation in vitro. In addition, cell cycle
      analysis demonstrated that linc-ITGB1-depleted cells accumulated in the G0/G1
      phase. HCCLM3 cells with linc-ITGB1 depletion exhibited significantly decreased
      migration and invasion abilities, when compared with control cells (P<0.05).
      These data suggest that linc-ITGB1 promotes HCC progression by inducing cell
      cycle arrest. Therefore, targeted therapy against linc-ITGB1 may be a novel
      strategy to treat HCC.

PMID- 29201167
TI  - CHAF1A, the largest subunit of the chromatin assembly factor 1 complex, regulates
      the growth of H1299 human non-small cell lung cancer cells by inducing G0/G1 cell
      cycle arrest.
AB  - Chromatin assembly factor 1 subunit A (CHAF1A) is the largest subunit of the
      chromatin assembly factor 1 (CAF-1) complex that is implicated in the assembly of
      nucleosomes on newly synthesized DNA. The aim of the present study was to
      determine its expression and biological function in non-small cell lung cancer
      (NSCLC). The current study examined the levels of CHAF1A expression in 22 samples
      of NSCLC and corresponding normal lung tissues. Subsequently, endogenous CHAF1A
      expression in H1299 NSCLC cells was knocked down via lentiviral delivery of
      CHAF1A-targeting short hairpin RNA (shRNA), and cell proliferation, colony
      formation and cell cycle distribution were measured. The results demonstrated
      that levels of CHAF1A mRNA level were ~3-fold greater in NSCLC samples compared
      with adjacent normal tissues (P<0.05). shRNA-mediated silencing of CHAF1A
      significantly inhibited the proliferation and colony formation of H1299 cells,
      compared wirh the delivery of control shRNA (P<0.05). Furthermore, CHAF1A shRNA
      transduced cells exhibited a significant increase in the percentage of S-phase
      cells and a significant decrease in the percentage of cells at the G0/G1 and G2/M
      phases, compared with control cells (P<0.05). Additionally, CHAF1A knockdown
      significantly decreased the expression of cyclin D1, cyclin-dependent kinase 2
      and S-phase kinase-associated protein 2, and increased the expression of p21 and
      p27. This indicates that CHAF1A is upregulated in NSCLC and that its silencing
      suppresses the proliferation and colony formation of NSCLC cells, potentially by
      inducing G0/G1 cell cycle arrest. CHAF1A may therefore represent a potential
      therapeutic target to treat NSCLC.

PMID- 29201169
TI  - p63 inhibits CD44+/CD24- cell proliferation and chemoresistance in papillary
      thyroid carcinoma cells.
AB  - Thyroid cancer typically has a good prognosis; however, the risks of recurrence
      and chemoresistance associated with thyroid cancer remain a cause for concern.
      Papillary thyroid carcinoma (PTC) comprises 80% of all cases of thyroid
      carcinoma. A previous study reported that cluster of differentiation (CD)
      44+/CD24- PTC cells may contribute to PTC recurrence and chemoresistance;
      however, the underlying molecular mechanisms remain elusive. In the present
      study, CD44+/CD24- cells were isolated from the TPC-1 PTC cell line and
      biological function assays revealed that CD44+/CD24- cells were significantly
      more proliferative and chemoresistant compared with CD44-/CD24- cells.
      Furthermore, the expression level of p63 was demonstrated to be negatively
      correlated with the expression of CD44 in PTC cells. The role of p63 in
      CD44+/CD24- cell proliferation and chemoresistance was investigated and, the
      ectopic expression of p63 was observed to significantly inhibit CD44+/CD24- cell
      proliferation and chemoresistance in vitro and in vivo. In conclusion, the
      present study indicated that CD44+/CD24- cells contribute to PTC proliferation
      and chemoresistance and that the suppression of p63 in CD44+/CD24- cells
      contributes to these effects.

PMID- 29201170
TI  - A network pharmacology approach to investigate the pharmacological effects of
      Guizhi Fuling Wan on uterine fibroids.
AB  - To investigate the pharmacological mechanism of Guizhi Fuling Wan (GFW) in the
      treatment of uterine fibroids, a network pharmacology approach was used.
      Information on GFW compounds was collected from traditional Chinese medicine
      (TCM) databases, and input into PharmMapper to identify the compound targets.
      Genes associated with uterine fibroids genes were then obtained from the
      GeneCards and Online Mendelian Inheritance in Man databases. The interaction data
      of the targets and other human proteins was also collected from the STRING and
      IntAct databases. The target data were input into the Database for Annotation,
      Visualization and Integrated Discovery for gene ontology (GO) and pathway
      enrichment analyses. Networks of the above information were constructed and
      analyzed using Cytoscape. The following networks were compiled: A compound
      compound target network of GFW; a herb-compound target-uterine fibroids target
      network of GWF; and a compound target-uterine fibroids target-other human
      proteins protein-protein interaction network, which were subjected to GO and
      pathway enrichment analyses. According to this approach, a number of novel
      signaling pathways and biological processes underlying the effects of GFW on
      uterine fibroids were identified, including the negative regulation of smooth
      muscle cell proliferation, apoptosis, and the Ras, wingless-type, epidermal
      growth factor and insulin-like growth factor-1 signaling pathways. This network
      pharmacology approach may aid the systematical study of herbal formulae and make
      TCM drug discovery more predictable.

PMID- 29201171
TI  - An integrated bioinformatical analysis of miR-19a target genes in multiple
      myeloma.
AB  - MicroRNA (miR)-19a, as an oncomiR, has been studied in several types of cancer;
      however, its role in the development and progression of multiple myeloma (MM)
      remains unclear. The present study used a bioinformatics approach to investigate
      the involvement of miR-19a in MM. miR-19a targets were predicted using target
      prediction programs, followed by screening for differentially expressed genes in
      MM. The function of these genes was then annotated using gene ontology term
      enrichment, signaling pathway enrichment and protein-protein interaction (PPI)
      analysis. In addition, natural language processing (NLP) was performed to
      identify genes associated with MM. A total of 715 putative targets of miR-19a
      were identified in the present study, of which 40 were experimentally validated.
      A total of 121 genes were identified to be differentially expressed in MM,
      including 80 upregulated genes and 41 downregulated genes. Among the
      differentially expressed genes, ras homolog family member B, clathrin heavy
      chain, prosaposin and protein phosphatase 6 regulatory subunit 2 were predicted
      target genes of miR-19a. The results of NLP revealed that 2 of the differentially
      expressed genes, Y-box binding protein 1 and TP53 regulated inhibitor of
      apoptosis 1, were reported to be associated with MM. In addition, 41 target genes
      of miR-19a were identified to be associated with the development and progression
      of MM. These results may aid in understanding the molecular mechanisms of miR-19a
      in the development and progression of MM. In addition, the results of the present
      study indicate that targets genes of miR-19a are potential candidate biomarkers
      for MM.

PMID- 29201172
TI  - Construction of a novel vector expressing Survivin-shRNA and fusion suicide gene
      yCDglyTK and its application in inhibiting proliferation and migration of colon
      cancer cells.
AB  - Despite progress achieved in cancer chemotherapy in recent decades, adverse
      effects remain a limiting factor for a number of patients with colorectal cancer,
      suggesting the requirement for novel therapeutic strategies. Gene therapy appears
      to be a promising strategy for treating cancer. The present study aimed to
      investigate the anti-tumor effect of a combined gene therapy, using Survivin
      downregulation by RNAi and a fusion suicide gene yCDglyTK therapy system. A
      triple-gene vector expressing Survivin-targeted small hairpin RNA (Survivin
      shRNA) and fusion suicide gene yCDglyTK was constructed, and administered to
      HCT116 cells. Survivin expression decreased significantly and yCDglyTK fusion
      gene expression was confirmed by both reverse transcription-quantitative
      polymerase chain reaction and western blot analysis. Introduction of Survivin
      shRNA into yCDglyTK/prodrug system eradicated colon cancer cells and induced
      apoptosis more effectively. Furthermore, this therapeutic system is able to
      inhibit the migration of HCT116 cells. These results indicate that the
      recombinant plasmid may serve as a novel gene therapy approach to treat
      colorectal carcinoma.

PMID- 29201173
TI  - Serological evaluation of antigen Tp0693 for diagnosis of syphilis.
AB  - The aim of the present study was to evaluate the diagnostic value of the
      Treponema pallidum (Tp) antigen Tp0693 for syphilis. ELISA was used to examine
      the serum levels of Tp0693. The sample-to-cutoff ratio (S/CO) value was used to
      generate a receiver operating characteristic (ROC) curve. A correlation analysis
      was performed to compare the detection efficacy of Tp0693-specific ELISA,
      Treponema pallidum Particle Agglutination (TPPA), Tolulized Red Unheated Serum
      test (TRUST) and LiZhuTM Tp-ELISA. The area under the ROC curve was 0.99,
      indicating good diagnostic efficacy. When the diagnostic specificity reached
      100%, the diagnostic sensitivity was up to 93.5%. Tp0693-specific ELISA results
      were not correlated with those of TPPA, TRUST and LiZhuTM Tp-ELISA (correlation
      coefficient, 0.122, 0.114 and 0.025, respectively). The latent syphilis rate was
      highest (12%, 9/75) for all syphilis specimens with a S/CO in the grey area. In
      conclusion, for syphilis specimens with a S/CO in the grey area, TPPA should be
      used for further confirmation of the diagnosis. Tp0693 may be used as a
      diagnostic antigen for syphilis; however, further study regarding its potential
      use is required.

PMID- 29201174
TI  - Effects of activated carbon N-acetylcysteine sustained-release microcapsule on
      dipeptidyl peptidase IV expression in young rats with non-alcoholic fatty liver
      disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) in children has become the most common
      liver disease influencing adolescent health and one of the most influencing
      chronic liver diseases among children in Chinese wealthy families, particularly
      in coastal regions. However, the medicine available for the treatment of NAFLD is
      deficient. In order to solve this problem, our team studied the activated carbon
      N-acetylcysteine (NAC) sustained-release microcapsule, which improves the
      oxidation resistance, bioavailability and drug stability of acetylcysteine and
      reduces toxic and side effects. In addition, it accords with the characteristics
      of medication in infants and children. The present study mainly discusses whether
      the activated carbon NAC sustained-release microcapsule has effects on dipeptidyl
      peptidase IV (DPPIV) activity and protein in young rats with NAFLD, and whether
      it has the effect of an DPPIV inhibitor, hoping to provide new thoughts and
      methods with respect of basic studies on young rats with NAFLD/non-alcoholic
      steatohepatitis.

PMID- 29201175
TI  - Anti-inflammatory effects of Fagopyrum cymosum administered as a potential drug
      for ulcerative colitis.
AB  - Fagopyrum cymosum (Trev.) Meisn (Fag), which belongs to the Polygonaceae family,
      has been widely used to treat inflammatory diseases. Previous studies have
      revealed that Fag components exhibit anti-inflammatory activities; however, their
      potential use in treating inflammatory bowel disease (IBD) has not been explored.
      In the present study, mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced
      colitis were used as a model of IBD. Fag extract was orally administered for 3
      days following the induction of colitis and the conventional drug,
      salicylazosulfapyridine (SASP), was used as a control. The results revealed that
      Fag significantly ameliorated TNBS-induced body weight loss and colonic
      shortening in mice (P<0.05). Furthermore, Fag suppressed levels of
      proinflammatory cytokines and reduced macrophage infiltration into colonic
      tissues (P<0.05). To further verify the anti-inflammatory effects of Fag at the
      molecular level, a murine macrophage cell line, Raw264.7, was used. Nuclear
      translocation of nuclear factor (NF)-kappaB p65 and the phosphorylation of
      inhibitor of NF-kappaB (IkappaB) were assessed using western blotting. The
      results demonstrated that Fag inhibited the production of proinflammatory
      cytokines via inhibiting NF-kappaB p65 nuclear translocation and IkappaB
      phosphorylation (P<0.05). Furthermore, the clinical study results revealed that
      Fag had significantly fewer side effects (P<0.05) and served as a better anti
      inflammatory drug for ulcerative colitis compared with SASP.

PMID- 29201176
TI  - In vivo and in vitro studies on the roles of p38 mitogen-activated protein kinase
      and NADPH-cytochrome P450 reductase in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disease with an
      increasing morbidity rate. As one of the most important signaling pathways that
      responds to inflammation and degeneration, the p38 mitogen-activated protein
      kinase (MAPK) signaling pathway is active in the cortexes of AD mice. At the
      cellular level the same effect can be observed with p38 MAPK when induced by
      amyloid beta (Abeta)1-42, a 42-residue Abeta fragment. Inhibition of p38 MAPK in
      the present study protected SH-SY5Y cells from the toxicity of Abeta1-42, and
      alleviated the formation of senile plaques and cognitive impairment in AD mice.
      The expression of cytochrome P450 reductase (CPR) in the brains of mice with AD,
      in addition to Abeta1-42-treated SH-SY5Y cells, also increased. However, the
      inhibition of CPR did not protect SH-SY5Y cells from the toxicity of Abeta1-42.
      The results of the present study suggest that p38 MAPK is a potential therapeutic
      target for the treatment of AD. In addition, the main enzyme that metabolizes
      drugs, CPR, could serve a more complex role in AD.

PMID- 29201177
TI  - Diagnostic value of 64-slice spiral computed tomography imaging of the urinary
      tract during the excretory phase for urinary tract obstruction.
AB  - The present study aimed to assess the diagnostic value of 64-slice spiral
      computed tomography (CT) imaging of the urinary tract during the excretory phase
      for urinary tract obstruction. CT imaging of the urinary tract during the
      excretory phase was performed in 46 patients that had been diagnosed with urinary
      tract obstruction by B-mode ultrasound imaging or clinical manifestations. It was
      demonstrated that out of the 46 patients, 18 had pelvic and ureteral calculi, 12
      cases had congenital malformations, 3 had ureteral stricture caused by urinary
      tract infection and 13 cases had malignant tumors of the urinary tract. The
      average X-ray dose planned for the standard CT scan of the urinary tract group 1
      was 14.11+/-5.45 mSv, while the actual X-ray dose administered for the CT scan
      during the excretory phase group 2 was 9.01+/-4.56 mSv. The difference between
      the two groups was statistically significant (t=15.36; P<0.01). The results of
      the present study indicate that CT scanning of the urinary tract during the
      excretory phase has a high diagnostic value for urinary tract obstruction.

PMID- 29201178
TI  - Analgesic therapy improves arterial endothelial function following non
      cardiovascular surgery: A randomized, placebo-controlled trial.
AB  - Pain subsequent to non-cardiac surgery may affect the endothelial function, which
      in turn contributes to myocardial injury (MI). The present study examined whether
      effective pain control is able to improve the postoperative endothelial function.
      Patients (n=160) undergoing laparoscopic cholecystectomy were randomly assigned
      into two groups, treated with tramadol analgesic or saline (placebo) following
      surgery. On preoperative day 1 (baseline) and postoperatively at 2 h, 1 day and 5
      days, pain was assessed on a visual analogue scale (VAS), and B-mode ultrasound
      was used to measure brachial endothelium-dependent flow-mediated dilation (FMD)
      and nitroglycerin-induced dilation. At 2 h postoperatively, the FMD in the two
      groups was significantly lower compared with that at the other three time points
      (P<=0.005), while VAS was significantly higher (P<0.05). Patients in the tramadol
      group presented significantly reduced VAS values in comparison with those in the
      placebo group at 2 h and 1 day postoperatively (P=0.013 and 0.031, respectively),
      as well as significantly higher FMD at 2 h (6.7+/-1.5 vs. 6.0+/-1.7%; P=0.001)
      and 1 day postoperatively (7.3+/-1.3 vs. 6.9+/-1.4%; P=0.03). A VAS score of <5
      was independently associated with postoperative FMD of >=7 (odds ratio, 2.5; 95%
      confidence interval, 1.0-6.0; P=0.047). Backward multivariate linear regression
      also demonstrated that FMD was independently correlated with age and VAS score
      (B=-1.403, P=0.011; B=-0.579, P=0.003). The response to nitroglycerin-induced
      dilation remained stable in all patients at baseline and at all postoperative
      time points. In conclusion, analgesic treatment may improve the arterial
      endothelial function following non-cardiac surgery, which may help prevent
      postoperative MI.

PMID- 29201179
TI  - Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem
      like cells via induction of lncRNA HOTAIR.
AB  - Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma
      of the pancreas, despite the high risk of chemoresistance as a major
      disadvantage. In the past few years, significant advances have been made in the
      field of pancreatic cancer stem-like cells (CSCs) and their critical roles in
      drug resistance, invasion and metastasis, which are tightly regulated by long non
      coding RNAs (lncRNAs). The present study demonstrated that HOX antisense
      intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line
      PANC-1 and its enriched CSC sub-population. However, after gemcitabine treatment,
      the expression levels of HOTAIR in CSCs were induced, but not in PANC-1 cells.
      HOTAIR induced by gemcitabine failed to cause chemoresistance, but promoted the
      clonogenicity, proliferation and migration of the cells. By introducing HOTAIR
      using lentivirus, chemoresistance was induced and the self-renewal capacity,
      proliferation and migration were significantly promoted. By contrast, HOTAIR
      knockdown in PANC-1 CSCs treated with or without gemcitabine decreased the cell
      proliferation, altered the cell cycle progression and induced apoptosis,
      demonstrating its critical roles in regulating the malignant character of PANC-1
      CSCs. In conclusion, the present study demonstrated that HOTAIR may be induced by
      gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and
      promoting the self-renewal capacity, proliferation and migration of PANC-1 CSCs,
      which supports its potential application as a novel therapeutic approach for
      pancreatic cancer.

PMID- 29201180
TI  - Rapid visual detection of binary toxin producing Clostridium difficile by loop
      mediated isothermal amplification.
AB  - The binary toxin Clostridium difficile transferase (CDT) is frequently observed
      in C. difficile strains and is associated with an increased severity of C.
      difficile infection. CDT-producing C. difficile infections cause higher fatality
      rates than infections with CDT negative isolates. Thus, the rapid and accurate
      identification of a CDT positive C. difficile infection is critical for effective
      treatment. The present study demonstrates how loop-mediated isothermal
      amplification (LAMP) can be used to detect CDT-producing C. difficile based on
      visual observation. This is a low complexity, rapid molecular method that has the
      potential to be used within a point of care setting. The specificity and
      sensitivity of the primers in the LAMP reactions for CDT detection were
      determined using two different methods, a real-time turbidity monitor and visual
      detection after the addition of calcein to the reaction tube. The results
      revealed that target DNA was amplified and visualized by these two detection
      methods within 60 min at a temperature of 60 degrees C. The sensitivity of the
      LAMP assay was identified to be 10-fold greater than that of polymerase chain
      reaction analysis. When 25 alternative bacterial strains lacking CDT were tested,
      the results of the amplification were negative, confirming the specificity of the
      primers. In conclusion, the visual LAMP method established in the present study
      may be a rapid, reliable and cost-effective tool for detecting CDT-producing C.
      difficile strains at the point of care.

PMID- 29200942
TI  - Measurement of multi-particle azimuthal correlations in pp, p + Pb and low
      multiplicity Pb + Pb collisions with the ATLAS detector.
AB  - Multi-particle cumulants and corresponding Fourier harmonics are measured for
      azimuthal angle distributions of charged particles in [Formula: see text]
      collisions at [Formula: see text] = 5.02 and 13 TeV and in [Formula: see text] +
      Pb collisions at [Formula: see text] = 5.02 TeV, and compared to the results
      obtained for low-multiplicity [Formula: see text] collisions at [Formula: see
      text] = 2.76 TeV. These measurements aim to assess the collective nature of
      particle production. The measurements of multi-particle cumulants confirm the
      evidence for collective phenomena in [Formula: see text] + Pb and low
      multiplicity [Formula: see text] collisions. On the other hand, the [Formula: see
      text] results for four-particle cumulants do not demonstrate collective
      behaviour, indicating that they may be biased by contributions from non-flow
      correlations. A comparison of multi-particle cumulants and derived Fourier
      harmonics across different collision systems is presented as a function of the
      charged-particle multiplicity. For a given multiplicity, the measured Fourier
      harmonics are largest in [Formula: see text], smaller in [Formula: see text] + Pb
      and smallest in [Formula: see text] collisions. The [Formula: see text] results
      show no dependence on the collision energy, nor on the multiplicity.

PMID- 29201181
TI  - Long-term exposure to ethanol downregulates tight junction proteins through the
      protein kinase Calpha signaling pathway in human cerebral microvascular
      endothelial cells.
AB  - Brain microvascular endothelial cells (BMECs) are the primary component of the
      blood-brain barrier (BBB). Tight junction (TJ) proteins, including claudin,
      occludin and zonula occludens (ZO)-1, ZO-2 and ZO-3, maintain the structural
      integrity of BMECs. Ethanol activates the assembly and disassembly of TJs, which
      is a process that is regulated by protein kinase C (PKC). In addition, ethanol
      treatment leads to the loss of structural integrity, which damages the
      permeability of the BBB and subsequently affects central nervous system
      homeostasis, thus allowing additional substances to enter the brain. However, the
      mechanisms underlying ethanol-induced loss of BBB structure remain unknown. It
      has been hypothesized that long-term exposure to ethanol reduces the expression
      of claudin-5, occludin and ZO-1 via the PKC signaling pathway, thereby affecting
      BBB structural integrity. In the current study, the human cerebral microvascular
      endothelial cell line, HCMEC/D3, was treated with 50, 100, 200 and 400 mM ethanol
      for 24, 48 and 72 h. Cell viability was determined using an MTS assay. The
      expression of claudin-5, occludin and ZO-1 protein and mRNA was measured using
      western blot analysis and reverse transcription-quantitative polymerase chain
      reaction, respectively. Following the pretreatment of HCMEC/D3 cells with the
      PKCalpha-specific inhibitor, safingol (10 umol/l), the expression of claudin-5,
      occludin, ZO-1 and phosphorylated (p)-PKCalpha was measured using western blot
      analysis, and PKCalpha localization was determined by immunofluorescence. With
      increasing concentrations of ethanol, the expression of claudin-5, occludin and
      ZO-1 protein decreased, while the expression of claudin-5, occludin and ZO-1 mRNA
      increased. Exposure to ethanol significantly increased the expression of p
      PKCalpha, whereas no significant effect on the expression of PKCalpha was
      observed. Following 48 h treatment with 200 mM ethanol, the expression of claudin
      5, occludin and ZO-1 protein was significantly decreased when compared with the
      control. By contrast, the expression of p-PKCalpha was increased, and increased
      translocation of PKCalpha from the cytoplasm to the nuclear membrane and nucleus
      was observed. In addition, the results demonstrated that safingol significantly
      reversed these effects of ethanol. In conclusion, long-term exposure to ethanol
      downregulates the expression of claudin-5, occludin and ZO-1 protein in HCMEC/D3
      s, and this effect may be mediated via activation of PKCalpha.

PMID- 29201182
TI  - The efficacy of gastrodin in combination with folate and vitamin B12 on patients
      with epilepsy after stroke and its effect on HMGB-1, IL-2 and IL-6 serum levels.
AB  - This study evaluated the efficacy of gastrodin in combination with folate (FOL)
      and vitamin-B12 (V-B12) on patients with epilepsy after stroke (EAS) and its
      effect on high-mobility group protein B1 (HMGB-1), interleukin-1 (IL-1), and IL-6
      serum levels. The clinical data of 92 EAS patients admitted for treatment between
      April, 2014 and March, 2016 were collected. These patients were randomly divided
      into control and observation groups (n=46 each) using computer software. Patients
      in the control group were administered only regular antiepileptic drugs, whereas
      observation group patients also received a combination of gastrodin, FOL and V
      B12. After treatment, we compared efficacy, frequency of epileptic seizure, and
      Montreal cognitive assessment (MoCA) scores. Serum homocysteine (HCY), FOL and V
      B12 levels were detected 3 months later. Enzyme-linked immunosorbent assay
      (ELISA) was used to detect changes in serum HMGB-1, IL-2 and IL-6 levels at one
      day before treatment and on the 7th, 21st, 30th and 90th days after treatment.
      Pearson's correlation coefficient was utilized to analyze the correlations of
      HMGB-1 with IL-2 and IL-6. The total treatment effectiveness rate was 95.65% in
      the observation group, which was significantly higher than the control group
      (73.91%, p<0.05). Epileptic seizure frequency and MoCA scores significantly
      improved in the observation group (p<0.05). Serum HCY levels were significantly
      lower, whereas FOL and V-B12 serum levels were significantly higher, at 3 months
      post-treatment start in the observation group relative to control group (p<0.05).
      After treatment, serum HMGB-1, IL-2 and IL-6 levels progressively decreased over
      time in both groups, but observation group levels were significantly lower than
      in control group (p<0.05). Pearson's correlation coefficient analysis showed that
      HMGB-1 levels were positively correlated with IL-2 and IL-6 levels. A combination
      of gastrodin, FOL and V-B12 for EAS can significantly improve inflammatory
      response symptoms, decrease HCY levels, and increase FOL and V-B12 levels in
      serum while effectively controlling epileptic seizures, thus exhibiting
      relatively better clinical efficacy. Therefore, this combination treatment is
      worthy of being promoted in clinical practice.

PMID- 29201184
TI  - The expression and significance of tyrosine hydroxylase in the brain tissue of
      Parkinsons disease rats.
AB  - The expression and significance of tyrosine hydroxylase (TH) in brain tissue of
      rats with Parkinson's disease (PD) were explored and analyzed. A total of 120
      clean-grade and healthy adult Wistar rats weighing 180-240 g were randomly
      divided equally into four groups according to the random number table method.
      Rats were sacrificed before and after the model establishment for 3, 6 or 8
      weeks. The number of revolutions in rats was observed and the relative expression
      of TH mRNA in brain tissue was measured. The relative expression of TH mRNA in
      left and right brain tissue of normal rats was respectively 1.039+/-0.112 and
      0.956+/-0.120. There was no significant difference in the expression of TH mRNA
      in either side of the brain tissue (p>0.05). With the extension of modeling time,
      the success rate of model establishment was significantly improved (p<0.05).
      After the model establishment for 6 weeks, the success rate peaked and there was
      no significant difference with 8 weeks (p>0.05). The relative expression of TH
      mRNA in the right brain was 0.053+/-0.082, which was significantly lower than
      that in the left brain tissue with 1.056+/-0.094 (p<0.05). After 6 weeks, the
      relative expression of TH mRNA in the left and right brain of PD rats was
      respectively 1.004+/-0.034 and 0.316+/-0.012, the expression of TH mRNA in right
      brain tissue was also significantly lower than that in the left (p<0.05).
      Similarly, after 8 weeks of the model establishment, the relative expression of
      TH mRNA in the right brain was significantly lower than that in the left brain
      tissue, with 0.395+/-0.041 and 1.021+/-0.057 (p<0.05). Compared with the control
      group, the expression of TH mRNA in both sides of the brain tissue decreased, and
      the expression of TH mRNA in the injured brain tissue was significantly lower
      than that in normal rats (p<0.05). The expression of TH mRNA in brain tissue of
      PD rats was lower than that in normal brain tissue, which may be related to the
      occurrence and development of PD.

PMID- 29201183
TI  - Role of miR-124a in T cell activation and immunity in AIDS patients.
AB  - The role of microRNA-124a (miR-124a) in the regulation of T cell activation and
      immunity in patients with AIDS, was studied to provide new insights for the
      study, diagnosis, alleviation and treatment of AIDS. RT-qPCR technique was used
      to quantitatively analyze the expression of miR-124a in peripheral blood CD4+ T
      cells. Dual-luciferase reporter assay system was established to report possible
      regulatory relations between miR-124a and its potential target gene SIRT1. RT
      qPCR and western blot analysis were used to detect the expression level of mRNA
      and protein of the target genes in T cells. Normal CD4+ T cells from controls
      were transfected with miR-124a mimics and its negative control, and miR-124a
      inhibitor and its negative control were transfected into CD4+ T cells from
      patients with AIDS by T lymphocyte transfection kit to detect the relative
      expression level of SIRT1 mRNA and protein. The levels of interferon (IFN)-gamma,
      interleukin (IL)-10, transforming growth factor (TGF)-beta, IL-2, IL-4 and IL-6
      secreted by T helper cells were detected by enzyme-linked immunosorbent assay
      (ELISA). miR-124a was upregulated in CD4+ T cells of patients with AIDS. The
      results of firefly luciferase activity detection showed that miR-124a can
      directly interact with target gene SIRT1 and negatively regulate its expression.
      miR-124a mimics/inhibitor transfection experiments showed that overexpression of
      miR-124a in normal CD4+ T cells significantly reduced SIRT1 expression compared
      with control group, and the expression of miR-124a was positively correlated with
      IL-10 and TGF-beta expression and negatively correlated with IFN-gamma
      expression, but showed no correlation with other cytokines. In AIDS patients, the
      inhibition of expression of miR-124a in CD4+ T cells significantly increased the
      expression of SIRT, at the same time, the expression levels of IL-10 and TGF-beta
      were significantly decreased, while the expression level of IFN-gamma was
      significantly increased and no significant difference was found in the expression
      of other cytokines. The expression of miR-124a in CD4+ T cells of AIDS patients
      was upregulated and the Th2 type CD4+ T cells are activated by SIRT1 expression
      inhibition, which in turn enhance the immunity of HIV-infected cells. Our study
      provides a new molecular target for the diagnosis, alleviation and treatment of
      AIDS.

PMID- 29201187
TI  - Shuyu capsules relieve liver-qi depression by regulating ERK-CREB-BDNF signal
      pathway in central nervous system of rat.
AB  - The purpose of this study was to investigate the possible therapeutic mechanism
      of Shuyu capsules in liver-qi depression. Liver-qi depression rats were prepared
      based on chronic unpredictable mild stress (CUMS) and delayed constraint. Rats
      were gavaged with Shuyu capsule, fluoxetine, Radix Bupleuri and Radix Paeoniae
      Alba to constrct rat models. Body weight test, sucrose preference test and open
      field test were applied to test rat models. Western blot analysis and
      quantitative real-time PCR was applied to determine the relative expression of
      extracellular signal-regulated protein kinase (ERK), cyclic AMP response element
      binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in
      hippocampus and frontal lobe tissues. ELISA was used to detect the content of
      BDNF in serum. Body weight, sugar intake and total distance were significantly
      decreased in depression group compared with control. The four drugs significantly
      increased levels of these factors. Compared with control group, ERK, CREB and
      BDNF expression were significantly decreased in depression group in both
      hippocampus and frontal lobe tissues at both mRNA and protein level. Shuyu
      capsule and fluoxetine group showed a significant increase in the expression of
      ERK, CREB and BDNF at mRNA, p-ERK and p-BDNF at protein level. Compared with
      Radix Paeoniae Alba, Radix Bupleuri were better in the rescue of ERK, CREB and
      BDNF expression. In conclusion, the pathogenesis of liver-qi depression
      associated with lower expression of ERK, CREB and BDNF in hippocampus and
      frontal. Shuyu capsule and main constitution alleviated the depressive-like
      behaviors and reversed the disruptions of the p-ERK, p-CREB and BDNF in stressed
      rats.

PMID- 29201192
TI  - Daidzein ameliorates spinal cord ischemia/reperfusion injury-induced neurological
      function deficits in Sprague-Dawley rats through PI3K/Akt signaling pathway.
AB  - Daidzein (DZ) has a broad spectrum of biological activities, including
      antioxidant, anti-inflammatory and anticancer as well as cardio- and
      hepatoprotective properties. The present study was designed to elucidate the in
      depth mechanism underlying the neuroprotective efficacy of DZ against spinal cord
      ischemic/reperfusion injury (SCII) in a rat model by comparison with the standard
      neuroprotective agent methylprednisolone (MP). A total of 48 rats were divided
      into four groups of twelve rats in each (n=12). In sham-operated group (Control)
      group, rats received only saline (Fogarty catheter was inserted without balloon
      inflation), whereas rats in the SCII induction group (SCII) were subjected to
      SCII insult by insertion of a Fogarty balloon catheter, which was inflated in the
      descending thoracic aorta to cause an occlusion. A proportion of rats was treated
      with DZ (20 mg/kg; DZ+SCII group) or MP (50 mg/kg; MP+SCII group) for seven days
      prior to and after SCII. The locomotor function (neurological activity) and
      antioxidant levels (superoxide dismutase and catalase) levels were significantly
      improved upon treatment with DZ and MP in comparison with those in the SCII
      group. A concomitant decline in edema, inflammatory markers (myeloperoxidase,
      tumor necrosis factor-alpha and nuclear factor kappaB p65), the apoptotic marker
      caspase-3 and the number of cells with terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling was also observed in the DZ and MP groups. The
      protein levels of phosphoinositide-3 kinase (PI3K), the phosphorylated Akt/Akt
      ratio and B-cell lymphoma 2 (Bcl-2) were substantially downregulated, while Bcl-2
      associated X protein levels were upregulated SCII insult group, which was
      inhibited by treatment with DZ. To conclude, pre-treatment with DZ significantly
      improved the neurological function by upregulating PI3K/Akt signaling and thereby
      considerably attenuating the inflammatory response and apoptosis, thus
      maintaining the neuronal count in an SCII-induced rat model.

PMID- 29201193
TI  - Effect of different treatments and alcohol addiction on gut microbiota in minimal
      hepatic encephalopathy patients.
AB  - Minimal hepatic encephalopathy (MHE) is caused by dysbiosis of gut microbiota,
      particularly the ammonia-producing bacteria. Given the efficacy of certain
      treatments on MHE and the connection between alcoholism and MHE, a thorough
      understanding of how these strategies affect the gut microbiota in patients
      (alcoholic or non-alcoholic) will facilitate the assessment of their efficacy in
      the reshaping of gut microbiota. In the present study, a metagenomics approach
      was adopted to reveal alterations in gut microbiota of 14 MHE patients following
      treatment with rifaximin alone or rifaximin plus probiotics. Patients were
      grouped into the alcoholic and non-alcoholic groups to examine differences in
      terms of their response to treatment. Treatment reduced the overall microbiota
      diversity and decreased the abundance of certain ammonia-producing bacteria, such
      as Clostridium, with the treatment of rifaximin plus probiotics presenting a more
      apparent effect. Non-alcoholic MHE patients responded better to the treatment, as
      they presented greater reduction in microbiota diversity and a more consistent
      decline in certain ammonia-producing bacteria genera (such as Clostridium and
      Streptococcus) belonging to the Firmicutes phylum. In conclusion, treatment with
      rifaximin alone and rifaximin plus probiotics exhibited a different effect in
      different MHE patients, decreasing the overall gut microbiota diversity to
      various extents and reshaping microbiota in different ways. Furthermore, non
      alcoholic MHE patients responded better to treatment in microbiota alterations.

PMID- 29201185
TI  - Relationship of SOCS3 and TGF-beta with IDO expression in early pregnancy
      chorionic villi and decidua.
AB  - We aimed to investigate the expression of suppressors cytokine signaling (SOCS)
      3, transforming growth factor (TGF)-beta and indoleamine 2,3-dioxygense (IDO) and
      to analyse the relationship of SOCS3 and TGF-beta with IDO expression in early
      pregnancy chorionic villi and decidua in the maternal-fetal interface. Western
      blot analysis and immunohistochemical method were used to detect the expression
      of TGF-beta, SOCS3 and IDO in chorionic villi and decidua tissues of normal
      pregnant women. SOCS3, TGF-beta and IDO protein was identified in chorionic villi
      and decidua tissues of normal pregnant women and there was a negative correlation
      between the expression of IDO and SOCS3, but TGF-beta expression was positively
      correlated with IDO expression. The levels of IDO expression in the decidua from
      normal pregnancies were significantly higher than those in chorionic villi, while
      the expression of SOCS3 was no significant difference between decidua and
      chorionic villi. In normal physiological state of pregnancy, SOCS3 and TGF-beta
      may be involved in the regulation of immune tolerance by positive or negative
      regulation of IDO expression at maternal fetal interface.

PMID- 29201191
TI  - Extended magnetic resonance imaging studies on the effect of classically
      activated microglia transplantation on white matter regeneration following spinal
      cord focal injury in adult rats.
AB  - Spinal cord injuries are still a serious problem for regenerative medicine.
      Previous research has demonstrated that activated microglia accumulate in spinal
      lesions, influencing the injured tissues in various ways. Therefore,
      transplantation of activated microglia may have a beneficial role in the
      regeneration of the nervous system. The present study examined the influence of
      transplanted activated microglial cells in adult rats with injured spinal cords.
      Rats were randomly divided into an experimental (M) and control (C) group, and
      were subjected to non-laminectomy focal injury of spinal cord white matter by
      means of a high-pressured air stream. In group M, activated cultured microglial
      cells were injected twice into the site of injury. Functional outcome and
      morphological features of regeneration were analyzed during a 12-week follow-up.
      The lesions were characterized by means of magnetic resonance imaging (MRI).
      Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A
      total of 12 weeks after surgery, spinal cords and brains were collected and
      subjected to histopathological and immunohistochemical examinations. Lesion sizes
      in the spinal cord were measured and the number of FG-positive neurons was
      counted. Rats in group M demonstrated significant improvement of locomotor
      performance when compared with group C (P<0.05). MRI analysis demonstrated
      moderate improvement in water diffusion along the spinal cord in the group M
      following microglia treatment, as compared with group C. The water diffusion
      perpendicular to the spinal cord in group M was closer to the reference values
      for a healthy spinal cord than it was in group C. The sizes of lesions were also
      significantly smaller in group M than in the group C (P<0.05). The number of
      brain stem and motor cortex FG-positive neurons in group M was significantly
      higher than in group C. The present study demonstrated that delivery of activated
      microglia directly into the injured spinal cord gives some positive effects for
      the regeneration of the white matter.

PMID- 29201186
TI  - Topically administered rhGM-CSF affects PPARbeta expression in the stasis zone.
AB  - Using a rat comb thermal damage model, we investigated the effects of topically
      administered recombinant human granulocyte-macrophage colony-stimulating factor
      (rhGM-CSF) on peroxisome proliferator-activated receptor PPARbeta expression. We
      created bilateral comb scald models on the backs of fifty Sprague-Dawley rats.
      The left sides of the backs served as the experimental group and the right sides
      served as the control group. The experimental group received topically applied
      rhGM-CSF hydrogel and the control group did not. The survival situations of the
      stasis zones were compared between the experimental and control groups on the
      1st, 3rd, 7th, 14th and 21st post-burn days. Tissues from the surviving stasis
      zones of both groups were collected at different time-points. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used
      to detect the PPARbeta mRNA and protein expression levels. Immunohistochemical
      methods were applied to detect the localization of PPARbeta protein expression.
      The results showed that, first, the tissue viability numbers for the stasis zones
      of the experimental group were significantly increased compared with those of the
      control group. Second, RT-PCR revealed that the PPARbeta mRNA expression first
      increased and then gradually declined in both groups. At all time-points, the
      expression level in the experimental group was increased compared with that in
      the control group and the highest expression levels were observed in both groups
      on the 3rd post-burn day. Third, western blot analysis revealed that the PPARbeta
      protein expression in both groups increased after thermal damage and then
      gradually decreased. PPARbeta protein expression in the experimental group was
      greater than that in the control group, and the highest expression quantities in
      both groups were observed on the 3rd post-burn day. In conclusion, rhGM-CSF
      hydrogel effectively promotes the expression of PPARbeta, and the hydrogel had a
      specific protective effect for the stasis zone.

PMID- 29201188
TI  - Simvastatin augments activation of liver regeneration through attenuating
      transforming growth factor-beta1 induced-apoptosis in obstructive jaundice rats.
AB  - Obstructive jaundice, owing to biliary obstruction, has been illustrated to
      trigger various biochemical, histological and immunological changes, leading to
      liver damage or even failure. The detailed molecular mechanism of simvastatin
      (Sim) involvement in liver regeneration during obstructive jaundice progression
      remains poorly elucidated. In the present study, an acute obstructive jaundice
      rat model was established by ligation and division of common bile duct, which was
      used to investigate the effects of Sim as a hepatoprotective treatment. Male
      Sprague-Dawley rats were randomly divided into four groups: Sham-operated, bile
      duct ligation (BDL) plus saline treatment [0.02 mg/kg/d, intraperitoneally
      (i.p.)], BDL plus low-dose Sim treatment (0.02 mg/kg, i.p.) and BDL plus high
      dose Sim treatment (0.2 mg/kg, i.p.). During this experiment, the BDL+normal
      saline (NS) group demonstrated increased levels of transforming growth factor
      beta1 (TGF-beta1) expression. Furthermore, Sim-treated animals demonstrated
      significantly downregulated TGF-beta1 expression and improved liver function vs.
      the BDL+NS group, indicating a TGF-beta1 antagonizing function. Additionally, Sim
      increased hepatocyte DNA synthesis in BDL rats compared to both the BDL+NS and
      Sham group. Apoptosis was increased in BDL+NS compared to the Sham group, and Sim
      markedly reduced hepatocyte apoptosis in the BDL group. Moreover, analysis of TGF
      beta1 signaling pathways demonstrated that there was an increased hepatic TGF
      beta1 and Smad3 expression in the BDL group, which was attenuated in the presence
      of Sim. In contrast to TGF-beta1, Sim induced the activity of the Smad7 (an
      inhibitor of TGF-beta1 signaling) mRNA and Smad7 protein expression. Sim displays
      hepatoprotective effects in liver cells via the upregulation of Smad7 expression
      and impaired TGF-beta signaling. Furthermore, the observations of the present
      study may provide evidence on the mechanism behind Sim blunting TGF-beta1
      signaling, which is used to ameliorate the complication of liver damage and
      reduce the mortality rates associated with obstructive jaundice.

PMID- 29201189
TI  - miR-30c may serve a role in endometriosis by targeting plasminogen activator
      inhibitor-1.
AB  - The present study aimed to investigate the role of miR-30c in endometriosis (EMs)
      and the underlying mechanism. The expression of miR-30c and plasminogen activator
      inhibitor type 1 (PAI-1) mRNA in EMs tissues was detected by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) and the expression
      of PAI-1 protein was detected by western blot analysis. The proliferation,
      migration, invasion and adhesion of endometrial stromal cells (ESCs) in different
      groups transfected with miR-30c mimic or inhibitor were compared. It was
      demonstrated that miR-30c expression in ectopic and eutopic endometriosis tissues
      were significantly lower than in normal endometrial tissue. However, PAI-1 mRNA
      expression in ectopic and eutopic endometrial tissues was higher than in normal
      endometrial tissues. Furthermore, the expression of PAI-1 protein was higher in
      ectopic and eutopic endometrosis tissues than in normal tissues. RT-qPCR results
      indicated that miR-30c expression was significantly increased or decreased in
      ESCs following transfection of mimic or inhibitor of miR-30c, respectively.
      Overexpression of miR-30c repressed the expression of PAI-1 mRNA and protein,
      while inhibition of miR-30c upregulated the expression of PAI-1 in ESCs. In
      addition, the invasion, migration, proliferation and adhesion of ESCs was
      repressed following the overexpression of miR-30c, whereas they were promoted
      when miR-30c expression was downregulated. The results of the present study
      indicated that miR-30c serves an important role in the development and
      progression of EMs by regulating the expression of PAI-1.

PMID- 29201190
TI  - Pigment epithelium-derived factor short peptides facilitate full-thickness
      cutaneous wound healing by promoting epithelial basal cell and hair follicle stem
      cell proliferation.
AB  - A previous study by our group showed that a 44-amino-acid fragment of pigment
      epithelium-derived factor (PEDF) facilitated corneal epithelial wound healing. In
      the present study this fragment was shortened to obtain peptides of 18, 20 and 29
      amino acids in length, and their promoting effects on the healing of full
      thickness skin wounds were assessed. Peptides were delivered periodically by
      topical application to punch wounds of mice. The wound healing speed was
      evaluated by measuring the reduction of wound areas at 4 and 7 days after injury.
      Histological analysis with Masson's trichrome staining was used to confirm
      epithelialization and dermal collagen deposition. Proliferation of epithelial
      basal cells was documented by 5-bromo-2'-deoxyuridine incorporation. Hair
      follicle stem cells were identified by immunostaining for leucine-rich repeat
      containing G protein-coupled receptor 6. The results indicated that the 20- and
      29-amino-acid short peptides significantly reduced the time required for wound
      healing compared to the vehicle. Histological analysis confirmed faster
      epithelial cell coverage of open wounds. Treatment with the PEDF peptide
      fragments also contributed to granulation, tissue formation by increasing the
      fibroblast population and enhancing collagen deposition in the dermis. Wounds
      treated with PEDF peptide fragments contained more basal cells proliferated in
      the epithelium. Moreover, hair follicle stem cells were also stimulated to
      proliferate by peptide exposure. In conclusion, the present study reported the
      identification of two short peptides that can enhance the healing of full
      thickness skin wounds following topical application. The underlying mechanisms
      may involve activation of basal cell proliferation and mobilization of hair
      follicle stem cells.

PMID- 29201194
TI  - Protective effect of zoledronic acid on articular cartilage and subchondral bone
      of rabbits with experimental knee osteoarthritis.
AB  - Subchondral bone reabsorption and remodeling are responsible for the initiation
      and progression of osteoarthritis (OA). Zoledronic acid (ZOL), a third-generation
      bisphosphonate (BIS), is an inhibitor of bone reabsorption. However, the
      intervention effect of ZOL on OA has not been fully characterized and remains to
      be directly demonstrated in animal experiments. The present study examined the
      microscopic and macroscopic changes in the anterior cruciate ligament transection
      (ACLT) model of OA in rabbits and evaluated the effects of ZOL on cartilage
      degeneration and subchondral bone loss. A total of 32 New Zealand white rabbits
      were randomly divided into four groups: High-, medium- and low-dose ZOL groups,
      which received an intravenous injection of 250, 50 and 10 ug/kg ZOL,
      respectively, after modeling, as well as an untreated group. The bone mineral
      density (BMD) of the knee joint was evaluated by dual-energy X-ray absorptiometry
      scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative
      measurement of cartilage was performed by a specialized magnetic resonance
      imaging (MRI) technique, including three-dimensional fat-suppressed spoil
      gradient-recalled sequence and T2 mapping. The rabbits were sacrificed by air
      embolism after anesthesia and both knee joints were harvested and evaluated by
      general and histological observation. Toluidine blue and hematoxylin and eosin
      staining were used to assess histological changes in the articular cartilage.
      Quantitative analysis of cartilage histopathology was performed according to the
      Mankin scoring system. The BMD of ACLT joints dropped after modeling, which was
      effectively suppressed by ZOL at the high and medium dose but not the low dose.
      MRI scans demonstrated that in the untreated group, articular cartilages on ACLT
      knees were thinner than those on normal knees. The high dose of ZOL preserved the
      cartilage tissue thickness more efficiently than the medium and low doses.
      Observation of specimens and pathological slices revealed that the articular
      cartilage degeneration in the high-dose ZOL group was lightest, while that in the
      medium- and low-dose ZOL group was moderate, and the untreated group exhibited
      the most severe defect. The untreated group had the highest Mankin score, whereas
      the high-dose ZOL group had the lowest score. In conclusion, ZOL increased the
      subchondral bone density, improved the microstructure and reduced the
      degeneration of articular cartilage in OA according to morphological as well as
      quantitative observation. ZOL exerted significant chondroprotective effects in a
      dose-dependent manner. A favorable chondroprotective effect was induced at the
      dose of 250 ug/kg. ZOL may represent a novel promising drug to complement the
      treatment of OA.

PMID- 29201195
TI  - Anti-nociceptive effect of dexmedetomidine in a rat model of monoarthritis via
      suppression of the TLR4/NF-kappaB p65 pathway.
AB  - As a therapeutic target for neuropathic pain, the anti-nociceptive effects of
      alpha 2-adrenoceptors (alpha2AR) have attracted attention. Dexmedetomidine (DEX),
      a potent and highly selective alpha2AR agonist, has exhibited significant
      analgesic effects in neuropathic pain, but the underlying mechanism has remained
      elusive. The present study investigated the effect of DEX on Toll-like receptor
      (TLR)4 and nuclear factor (NF)-kappaB p65 expression, as well as the production
      of pro-inflammatory cytokines. The rat monoarthritis (MA) model was induced by
      intra-articular injection of complete Freund's adjuvant (CFA) at the ankle joint.
      After induction of MA, the rats were intrathecally treated with normal saline or
      DEX (2.5 ug) for 3 consecutive days. The concentration of interleukin-1beta and 
      6 as well as tumor necrosis factor-alpha was examined by ELISA. The expression
      levels of TLR4 and NF-kappaB p65 were determined by western blot analysis and
      immunohistochemistry. The results indicated that the pro-inflammatory cytokines
      TLR4 and NF-kappaB p65 were significantly upregulated in MA rats. DEX treatment
      markedly reduced mechanical and thermal hyperalgesia, suppressed MA-induced
      elevation of the pro-inflammatory cytokines and inhibited the TLR4/NF-kappaB p65
      pathway, while these effects were blocked by pre-treatment with the selective
      alpha2AR antagonist BRL44408 (15 ug) at 30 min prior to CFA injection. These
      results suggested that DEX has an anti-nociceptive effect via suppressing the
      TLR4/NF-kappaB p65 pathway.

PMID- 29201196
TI  - Lycium barbarum polysaccharide protects against neurotoxicity via the Nrf2-HO-1
      pathway.
AB  - The incidence of neurodegenerative diseases including Alzheimer's and Parkinson's
      disease has markedly increased over the past few decades. Oxidative stress is
      considered to be a common pathophysiological condition resulting in
      neurotoxicity. Lycium barbarum polysaccharide (LBP) is the major active component
      of Lycium barbarum L., which exhibit potent antioxidant activity. The current
      study investigated the neuroprotective effects of LBP in H2O2-treated PC12 cells
      in vitro and in CoCl2-treated rats in vivo. It was determined that LBP
      concentration-dependently reversed the H2O2-induced increase in reactive oxygen
      species (ROS) levels, decrease in cell viability, increase in TUNEL-stained
      cells, increase in caspase-3 and -9 activity and decrease in mitochondrial
      membrane potential, indicating the amelioration of mitochondrial apoptosis.
      Furthermore, LBP inhibited the H2O2-induced decrease in nuclear factor erythroid
      2-related factor 2 (Nrf)2 and heme oxygenase (HO)-1 expression and binding of
      Nrf2 to the promoters of HO-1. Silencing of Nrf2 and inhibition of HO-1 by zinc
      protoporphyrin IX (ZnPP) reversed the protective effects of LBP against H2O2
      resulted neurotoxicity in PC12 cells. In CoCl2-treated rats, it was demonstrated
      that LBP decreased brain tissue apoptosis, reduced the time spent by rats finding
      the platform site, decreased escape latencies and reduced the distance traveled
      to find the platform. In addition, LBP inhibited the CoCl2-induced decrease of
      Nrf2 and HO-1 expression. Administration of ZnPP also suppressed the protective
      effects of LBP against CoCl2-resulted neurotoxicity in rats. Thus, the current
      study indicated that LBP exhibits protective effects against neurotoxicity by
      upregulating Nrf2/HO-1 signaling. These data may increase understanding regarding
      the neuroprotective activities of LBP.

PMID- 29201197
TI  - Calcitonin gene-related peptide has protective effect on brain injury induced by
      heat stroke in rats.
AB  - Heat stroke often leads to multiple organ dysfunction syndrome (MODS) with a
      neurological morbidity of 30%. Current studies suggested that pathophysiological
      responses to heat stroke may be due to a systemic inflammatory response syndrome
      and a series of peptidergic nerve reactions. The mechanisms underlying the high
      neurological morbidity in heat stroke have remained largely elusive. In recent
      years, calcitonin gene-related peptide (CGRP) has been considered to have a
      positive role in central nervous system injury. The present study investigated
      the influence of CGRP on brain injury induced by heat stroke. A rat model of heat
      stroke was established in a pre-warmed artificial climate chamber with a
      temperature of 35.5+/-0.5 degrees C and a relative humidity of 60+/-5%. The
      rectal core temperature (Tc) was monitored. Heat stress was halted at a Tc of no
      more than 41 degrees C A bolus injection of CGRP was administered to each rat in
      the HS+CGRP group and a bolus injection of CGRP8-37 was administered to each rat
      in the HS+CGRP8-37 group after heat stress. After 2 h, electroencephalograms were
      recorded and the pathological morphology of brain tissue as well as brain cell
      apoptosis and caspase-3 protein levels in the brain were measured. The EEG of
      rats in the HS+CGRP group was characterized by a short- to long-term alpha-wave
      and low-voltage beta-waves as well as a large amount of intermittent delta- and
      theta-waves. Compared with the HS group, the theta-wave decreased and the alpha
      wave increased significantly (P<0.05). Slight pathological damage of nerve cells
      appeared in the HS+CGRP group. Greater damage was observed in HS+CGRP8-37 group
      with neural cell shrinkage, volume reduction, nuclear pyknosis, disappearance of
      part of the nuclear membrane and cell necrosis. In the HS+CGRP group, apoptotic
      cells and caspase-3 protein in the brain were significantly decreased when
      compared with those in the HS group (P<0.05), while they were significantly
      increased in the HS+CGRP8-37 group (P<0.05 vs. HS group). The results of the
      present study reflected that CGRP has a protective effect on early-stage brain
      injury induced by heat stroke in rats.

PMID- 29201198
TI  - Comparison of the effect of rosuvastatin versus rosuvastatin/ezetimibe on markers
      of inflammation in patients with acute myocardial infarction.
AB  - Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C
      reactive protein (hsCRP), and the addition of ezetimibe to statins further
      reduces LDL-C and hsCRP. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a
      potentially important pathogenic factor participating in the progression of
      atherosclerosis. The aim of current study was to investigate how the addition of
      ezetimibe to rosuvastatin treatment affects reductions in LDL-C, hsCRP and Lp
      PLA2 in patients with acute myocardial infarction (AMI). A total of 135 patients
      were enrolled in the study within 24 h of AMI, and were randomized to receive 10
      mg rosuvastatin or 10 mg rosuvastatin plus 10 mg ezetimibe daily. HsCRP, Lp-PLA2,
      total cholesterol (TC), triglycerides (TG), LDL-C and high-density lipoprotein
      cholesterol (HDL-C) were determined at baseline and after 1, 3, 6 and 12 months
      of treatment. The addition of ezetimibe to rosuvastatin led to greater reduction
      of LDL-C compared with rosuvastatin monotherapy (from 3.00 to 1.19 mmol/l vs.
      2.93 to 1.49 mmol/l, respectively; P<0.05), as well as reduced levels of hsCRP
      (from 5.15 to 0.68 mg/l vs. 4.33 to 1.49 mg/l, respectively; P<0.05) and Lp-PLA2
      (from 333.13 to 79.07 mg/l vs. 327.95 to 123.62 mg/l, respectively; P<0.05). A
      positive association was identified between reductions of Lp-PLA2 and the changes
      of LDL-C (r=0.367; P=0.002). However, no significant correlation was observed
      between changes in Lp-PLA2 and hsCRP (r=0.264; P=0.512). The values of hsCRP and
      Lp-PLA2 appeared to increase during the first week after randomization, but
      dropped steeply to a lower level and remained stable thereafter. In conclusion,
      the addition of ezetimibe to rosuvastatin was demonstrated to further reduce LDL
      C, hsCRP and Lp-PLA2 compared with rosuvastatin monotherapy in patients with AMI.

PMID- 29201199
TI  - LYTAK1 attenuates proliferation of retinal pigment epithelial cells through TGF
      beta-mediated epithelial-mesenchymal transition via the ERK/AKT signaling
      pathway.
AB  - Retinal pigment epithelial (RPE) cells have crucial roles in the initiation and
      development of human ophthalmic diseases. Our previous study suggested that
      transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a
      potential target in the progression and pathogenesis of human proliferative
      vitreoretinopathy disease. The present study further analyzed the role of TAK1
      inhibitor, LYTAK1, in human RPE cells and explored the potential molecular
      mechanism of LYTAK1-mediated proliferation of human RPE cells. Proliferation of
      human RPE cells was investigated following treatment with LYTAK1 and knockdown of
      TGF-beta. TGF-beta-mediated epithelial-mesenchymal transition (EMT) through
      regulation of the extracellular signal-regulated kinase (ERK)/protein kinase B
      (AKT) signaling pathway was also explored to analyze the LYTAK1-mediated
      mechanism of proliferation in human RPE cells. The present results demonstrated
      that LYTAK1 administration suppressed TAK1 gene and protein expression in human
      RPE cells. LYTAK1 administration also inhibited proliferation and migration of
      human RPE cells in vitro. Outcomes indicated that LYTAK1 treatment downregulated
      expression levels of TGF-beta1 and EMT markers, including cadherin, fibronectin
      and alpha-smooth muscle actin in human RPE cells. Notably, results demonstrated
      that the ERK/AKT signal pathway was blocked by LYTAK1 in human RPE cells.
      Knockdown of TGF-beta markedly inhibited phosphorylation and activity of TAK1 and
      suppressed the LYTAK1-mediated ERK/AKT signaling pathway in RPE cells, which
      further canceled inhibition of RPE cell proliferation by LYTAK1. In conclusion,
      these findings indicated that LYTAK1 may inhibit RPE cell proliferation through
      the TGF-beta-mediated EMT/ERK/AKT signaling pathway, suggesting that TAK1 may be
      a potential target for the treatment of RPE diseases.

PMID- 29201200
TI  - Effect of a stilbene glycoside-rich extract from Polygoni Multiflori Radix on
      experimental non-alcoholic fatty liver disease based on principal component and
      orthogonal partial least squares discriminant analysis.
AB  - Polygoni Multiflori Radix is a traditional Chinese medicine used clinically to
      support the functions of the liver and kidneys and to treatment hyperlipidemia.
      In previous studies, an effective fraction, rich in 2,3,5,4'-tetrahydroxy
      stilbene-2-O-beta-D-glucoside (TSG), was separated from Polygoni Multiflori Radix
      and demonstrated hypolipidemic activity. The present study aimed to
      systematically assess the effect of this fraction on non-alcoholic fatty liver
      disease (NAFLD). A NAFLD model was established by feeding Sprague-Dawley rats a
      high-fat diet with 10% fructose solution for 18 weeks. Hematoxylin and eosin
      staining was applied for hepatic histopathological analysis. In addition, enzyme
      activities, lipid metabolism, inflammatory factors and insulin resistance indices
      were measured using a fully automatic blood biochemistry analyser and ELISA.
      Furthermore, cytochrome P450 2E1 (CYP2E1) and peroxisome proliferator-activated
      receptor alpha (PPARalpha) mRNA and protein expression were evaluated using
      reverse transcription-quantitative polymerase chain reaction and western blot
      analysis. Principal component analysis and orthogonal partial least squares
      discriminant analysis were used to analyse the data. The results revealed that
      the TSG-rich fraction (TSGP) significantly lowered the serum total cholesterol
      and triglyceride levels, and the liver free fatty acid, CYP2E1 mRNA and
      malondialdehyde levels, in addition to mitigating hepatic enlargement and
      alleviating liver steatosis. Furthermore, it upregulated PPARalpha mRNA
      expression in the liver tissue. The results indicated that TSGP exhibited a
      protective effect against NAFLD and the underlying mechanism may involve
      augmentation of anti-lipid peroxidation capacity via regulation of PPARalpha and
      CYP2E1-mediated pathways.

PMID- 29201201
TI  - Spatial and temporal expression of Smad signaling members during the development
      of mandibular condylar cartilage.
AB  - The present study aimed to explore the underlying developmental mechanism of
      mothers against decapentaplegic homolog (Smad) signaling in the development of
      mandibular condylar cartilage. To achieve this, the expression levels of Smad2,
      3, 4 and 7, and phosphorylated Smad2/3 were investigated at different time points
      in developing mandibular condylar cartilage. Mandibular condyles from C57BL/6J
      mice were dissected at the prenatal and postnatal stages. Serial sections were
      made and the distributions of Smad proteins were examined using
      immunohistochemical techniques intermittently between day 14.5 of gestation and
      postnatal day 7. All Smad proteins examined in the present study were expressed
      in the condylar blastema and during early chondrogenesis. At the postnatal stage,
      Smad2 and 4 were localized in proliferative and mineralized hypertrophic
      chondrocytes. Smad3 and 7 were expressed in proliferative and hypertrophic
      chondrocytes, including pre-hypertrophic and mineralized hypertrophic
      chondrocytes. Later, positive immunoreactivity of Smad3 reduced at postnatal day
      7. A similar expression pattern to Smad3 was observed for p-Smad2/3, but p
      Smad2/3 was located in the nuclei of proliferative chondrocytes. These results
      suggest that Smad signaling members are involved in the development of mandibular
      condylar cartilage. In addition, the spatial and temporal expression of these
      Smads indicate that Smad signaling is involved in regulating the differentiation
      of chondrocytes and endochondral ossification, in order to maintain normal
      chondrogenesis and morphogenesis of mandibular condylar cartilage.

PMID- 29201202
TI  - Ginsenoside Rg3 induces ginsenoside Rb1-comparable cardioprotective effects
      independent of reducing blood pressure in spontaneously hypertensive rats.
AB  - Ginsenoside Rg3 (Rg3) is a rare type of ginsenoside used as an anti-tumor
      medicine in China. Ginsenoside Rb1 (Rb1), which exhibits protective effects on
      the cardiovascular system, is similar to Rg3 in chemical structure. In the
      present study, Rb1 and Rg3 were administered for 6 weeks to spontaneously
      hypertensive rats (SHR) and their cardioprotective effects were assessed.
      According to echocardiography and histopathological examinations, the decrease in
      cardiac function and ventricular remodeling that occurred in SHR rats were
      attenuated by Rb1 and Rg3. However, tail-cuff blood pressure measurements
      indicated that Rb1 and Rg3 did not reduce blood pressure in SHR rats. The
      cardioprotective effects of Rb1 and Rg3 occurred independently of blood pressure
      reduction. Furthermore, immunohistochemistry (IHC) revealed that renin
      angiotensin system (RAS) activity in the myocardium of SHR was significantly
      attenuated by Rb1 and Rg3, whereas ELISA identified no significant changes of RAS
      activity in the serum. The results of IHC and reverse transcription-quantitative
      polymerase chain reaction demonstrated that levels of transforming growth factor
      beta1, tumor necrosis factor-alpha, interleukin-6, interleukin-1 and endothelian
      1 in the myocardium of SHR rats were reduced following Rb1 and Rg3 treatment.
      This may be due to the attenuation of RAS activity in the myocardium and the
      mechanisms of the cardioprotective effects of Rb1 and Rg3.

PMID- 29201203
TI  - Butanol extracts of Asparagus cochinchinensis fermented with Weissella cibaria
      inhibit iNOS-mediated COX-2 induction pathway and inflammatory cytokines in LPS
      stimulated RAW264.7 macrophage cells.
AB  - Roots of Asparagus cochinchinesis have been widely used to treat fever, cough,
      kidney disease, breast cancer, inflammatory and brain disease, although the
      effects of their fermented products have not been assessed until now. To
      investigate the anti-inflammatory effects on macrophages of a butanol extract
      from A. cochinchinensis roots fermented with Weissella cibaria (BAW), alterations
      in the inducible nitric oxide synthase (iNOS)-mediated cyclooxygenase-2 (COX-2)
      induction pathway and inflammatory cytokine expression were measured in
      lipopolysaccharide (LPS)-activated RAW264.7 cells following pretreatment with
      BAW. Briefly, W. cibaria was selected from two bacterial strains for the
      fermentation of A. cochinchinensis roots based on its hyaluronidase inhibition
      and NO suppression rates. Following fermentation with W. cibaria, the level of
      various key components including total phenols and protodioscin were
      significantly enhanced in BAW. In addition, BAW exhibited high free radical
      scavenging activity (IC50=31.62 ug/ml) and induced a decrease of intracellular
      ROS production in RAW264.7 cells following DCFH-DA staining. Significant
      suppressions in the expression level of important members of the iNOS-mediated
      COX-2 induction pathway and the phosphorylation of mitogen-activated protein
      kinase members were detected. The expressions of pro-inflammatory and anti
      inflammatory cytokines were recovered in BAW pretreated RAW264.7 cells. Overall,
      these results suggest that BAW may suppress inflammatory responses through
      differential regulation of the iNOS-mediated COX-2 induction pathway and
      inflammatory cytokine expressions in LPS-activated RAW264.7 cells.

PMID- 29201204
TI  - A rabbit model of implant-related osteomyelitis inoculated with biofilm after
      open femoral fracture.
AB  - Currently, animal models used in research on implant-associated osteomyelitis
      primarily use intramedullary fixation and initial inoculum of planktonic
      bacterial cells. However, these techniques have certain limitations, including
      lack of rotational stability and instable inoculation. To improve these models,
      the present study aimed to establish a novel rabbit model of implant-associated
      osteomyelitis using biofilm as the initial inoculum following plate fixation of
      the femoral fracture. A total of 24 New Zealand White rabbits were randomly
      divided into two equal groups. Osteotomy was performed at the right femoral shaft
      using a wire saw following fixation with a 5-hole stainless steel plate. The
      plates were not colonized with bacteria in group 1, but colonized with a biofilm
      of Staphylococcus aureus (American Type Culture Collection, 25923) in group 2.
      All the rabbits were sacrificed after 21 days for clinical, X-ray, micro-computed
      tomography and histological assessments of the severity of osteomyelitis.
      Scanning electron microscopy and confocal laser scanning microscopy were used for
      biofilm assessment. In group 2, pus formation, periosteal reaction, cortical
      destruction and absorption were observed in all the rabbits and biofilm formation
      was observed on all the plates. However, no pus formation was observed except for
      a slight inflammatory response and all the plates appeared clean without
      infection in group 1. The differences between the two groups were statistically
      significant regarding histologic scores and semi-quantification of the bacteria
      on the plates (P<0.001). In the present study, a novel rabbit model of infection
      following internal plate fixation of open fracture was successfully established,
      providing a novel tool for the study of implant-associated osteomyelitis.

PMID- 29201205
TI  - Bone engineering by cell sheet technology to repair mandibular defects.
AB  - Effectiveness of bone engineering by cell sheet technology to repair canine
      mandibular injuries was investigated. Cell sheets were produced from canine stem
      cells cultured by density gradient centrifugation and osteoblast induction. A
      scaffold surface of polylactic-co-glycolic acid (PLGA) copolymer was wrapped with
      cell sheets. Mandibular injuries were created in 12 healthy dogs followed by
      implantation of PLGA with (experimental group; n, 6) and without (control group;
      n, 6) cell sheets. The progression of the implants was examined at 3, 9, and 12
      weeks postoperative. At postoperative 12 weeks, the graft mostly replaced the new
      bone in the experimental group, compact similar to normal bone was formed at
      lingual position and the broken end of the bone was normally healed. The bone
      mass in the control group was 2.5, which was significantly lower than the 4.5 in
      the experimental group. The optical density of the new bone in the experimental
      group was significantly higher than that in the control group. The experimental
      group had more haversian canal and red bone marrow and contained a larger number
      of lamellar bone than the control group. Overall, satisfactory bone engineering
      containing lamellar bone can be established by cell sheet technology, which is an
      ideal method to repair mandibular injuries.

PMID- 29201206
TI  - Combined treatment of diabetic nephropathy with alprostadil and calcium
      dobesilate.
AB  - This study investigated the effects of alprostadil combined with calcium
      dobesilate on the treatment of diabetic nephropathy. We recruited 80 patients
      with diabetic nephropathy, who were randomly divided into experimental (n=40) and
      control (n=40) groups. Patients received high-quality low-protein diabetic diet
      intervention and subcutaneous injection of insulin to adjust blood glucose,
      combined with antihypertensive, antiplatelet drugs, and other comprehensive
      treatments. The control group received alprostadil and the experimental group
      received alprostadil combined with calcium dobesilate. Both groups were treated
      for 12 weeks as one treatment cycle. The time to remission of clinical symptoms
      such as mental fatigue and weakness, limb edema, soreness and swelling of waist
      and knee, cold limbs and limb numbness and pain was significantly shorter in the
      experimental group than that in the control group (p<0.05). After intervention,
      the blood levels of small molecular weight proteins, such as beta2-microglobulin
      (beta2-MG), cystatin C (CysC), and retinol binding protein (RBP), were
      significantly lower in the experimental group than those in the control group
      (p<0.05). The levels of the inflammatory cytokines tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP) were
      significantly lower in the experimental group than those in the control group
      (p<0.05). The levels of 25-hydroxyvitamin D and parathyroid hormone were
      significantly higher in the experimental group than those in the control group
      (p<0.05). The level of angiotensin II was lower in the experimental group than
      that in the control group (p<0.05) and the level of fasting serum insulin was
      significantly higher in the experimental group than that in the control group
      (p<0.05). The homeostasis model assessment of insulin resistance (HOMA-IR) index
      was lower in the experimental group than that in the control group (p<0.05). The
      levels of renal function indexes, blood urea nitrogen, creatinine and uric acid,
      in experimental group were lower than those in control group (p<0.05). The levels
      of brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF
      1) were significantly higher in both groups after the intervention than those
      before the intervention (p<0.05). The levels of BDNF and IGF-1 were higher in the
      experimental group than that in control group after intervention (p<0.05). The
      application of alprostadil combined with calcium dobesilate in patients with
      diabetic nephropathy can effectively relieve clinical symptoms, improve renal
      functions, reduce blood levels small proteins, alleviate the inflammatory
      response, and regulate the levels of BDNF and IGF-1, thus improving the clinical
      treatment effect.

PMID- 29201207
TI  - Clinical significance of novel biomarker NGAL in early diagnosis of acute renal
      injury.
AB  - The present study investigated the clinical significance of the novel biomarker
      neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of
      acute renal injury (AKI). Thirty-eight critically ill patients with acute renal
      injury treated at Zhengzhou No. 7 People's Hospital between December 2015 and
      November 2016 served as the AKI group (observation group). At the same time, 38
      critically ill patients without acute renal injury were also selected as the non
      AKI group (control group). Serum NGAL and creatinine (SCr) levels were measured
      by enzyme-linked immunosorbent assay (ELISA) at 2, 8, 12 and 24 h post-operation,
      whereas particle-enhanced turbidimetric immunoassay (PETIA) was used to quantify
      the levels of cysteine protease inhibitor cystatin C (CysC) in serum at 2, 8, 12
      and 24 h post-operation. The correlations between indicators were also analyzed,
      with ROC curves used to evaluate the diagnostic values of NGAL, SCr and CysC in
      AKI. No significant differences in SCr levels were found between the two groups
      at different time-points after operation (P>0.05), but NGAL and CysC levels in
      the observation group were significantly higher than in the control group
      (P<0.05). Pearson correlation coefficient analysis showed NGAL and CysC were
      positively correlated with Scr levels. For NGAL in early diagnosis, the area
      under the AKI curve was 0.904, the sensitivity was 90.2% and the specificity was
      89.5%; for CysC in early diagnosis, the area under the AKI curve was 0.806, the
      sensitivity was 79.2% and the specificity was 78.5%; for SCr in early diagnosis,
      the area under the AKI curve was 0.634, the sensitivity was 64.2% and the
      specificity was 62.5%. Therefore, NGAL demonstrated a satisfactory early
      predictive value for AKI and can be used as a biomarker for early AKI diagnosis.

PMID- 29201208
TI  - The content of hydrogen sulfide in plasma of cirrhosis rats combined with portal
      hypertension and the correlation with indexes of liver function and liver
      fibrosis.
AB  - The purpose of this study is to investigate the content of hydrogen sulfide (H2S)
      in plasma of cirrhosis rats combined with portal hypertension and the correlation
      with indexes of liver function and liver fibrosis. Thirty female Sprague-Dawley
      rats were randomly divided into normal control group (NC), liver cirrhosis group
      (LC) and cirrhosis + propargylglycine (PPG) group (LC+PPG). Cirrhosis and portal
      hypertension were induced by carbon tetrachloride. Rats in LC+PPG group were
      intraperitoneally injected with H2S synthase inhibitor PPG for one week. Portal
      vein catheterization was used to measure portal vein pressure (PVP), and plasma
      H2S content was determined by deproteinization. Liver function was measured by
      automatic biochemical analyzer, and the fibrosis index was determined by
      radioimmunoassay. Real-time PCR was used to detect the expression levels of type
      I and type III collagen mRNA in liver tissue. Compared with NC group, levels of
      plasma H2S were significantly decreased (P<0.01), while PVP, alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), laminin (LN),
      hyaluronic acid (HA), and expression levels of type III procollagen (PC III) and
      type I and type III collagen mRNAs were significantly increased in LC and LC+PPG
      groups (P<0.01). Compared with LC group, levels of plasma H2S were significantly
      decreased (P<0.01), while PVP, ALT, AST, LN, HA, and expression levels of PC III
      and type I and type III collagen mRNAs in LC+PPG group (P<0.05 or P<0.01). In
      conclusion, level of H2S was decreased and PVP was increased in cirrhosis rats,
      and H2S has the function of protecting liver function and anti-fibrosis.

PMID- 29201209
TI  - Correlation of the expression of miR-146a in peripheral blood mononuclear cells
      of patients with ankylosing spondylitis and inflammatory factors.
AB  - We investigated the expression of miR-146a in peripheral blood mononuclear cell
      (PBMC) of patients with ankylosing spondylitis (AS) and its correlation with
      inflammatory factors to explore the clinical significance. In total 45 patients
      with AS were selected at the Weifang People's Hospital from June, 2014 to
      January, 2016. At the same time, 30 healthy volunteers were also selected to
      serve as control group. Expression level of miR-146a in PBMC cells of patients in
      each group was detected by quantitative real-time-polymerase chain reaction (qRT
      PCR). Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta) and IL-6 in serum and the supernatant of culture medium of PBMC derived
      from each group were detected by enzyme-linked immunosorbent assay (ELISA).
      Correlations between expression level of miR-146a and serum inflammatory factors,
      and clinical indicators were analyzed. Clinical indicators included bath
      ankylosing spondylitis disease activity index (BASDAI), C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR) and duration of morning stiffness.
      Expression level of miR-146a in PBMC of AS patients was significantly higher than
      that of healthy control (P<0.01); levels of TNF-alpha, IL-1beta and IL-6 in serum
      and the supernatant of culture medium of PBMC derived from AS patients were
      significant compared to those of control group (P<0.01); expression of miR-146a
      in PBMC of patients with AS was positively correlated with the levels of TNF
      alpha, IL-1beta and IL-6 in serum (r=0.632, P<0.01; r=0.574, P<0.01; r=0.483,
      P<0.01). In addition, expression level of miR-146a in PBMC of patients with AS
      was positively correlated with BASDAI, ESR, CRP and duration of morning stiffness
      (r=0.551, P<0.01; r=0.738, P<0.01; r=0.685, P<0.01; r=0.497, P<0.01). Expression
      level of miR-146a in PBMC of AS patients was significantly increased and the
      expression level was positively correlated with the levels of TNF-alpha, IL-1beta
      and IL-6 in serum (P<0.05). In addition, expression level of miR-146a in PBMC of
      AS patients was also positively correlated with BASDAI, ESR, CRP and duration of
      morning stiffness. Those results suggest that miR-146a may be involved in the
      pathogenesis of AS, and the expression level of miR-146a in PBMC cells may be
      helpful for diagnosis of AS and judgment of disease activity.

PMID- 29201210
TI  - Protective effects of resveratrol on osteoporosis via activation of the SIRT1-NF
      kappaB signaling pathway in rats.
AB  - The aim of the present study was to determine the protective effects of
      resveratrol on a rat model of osteoporosis and examine the associated mechanisms
      of its action. Rats were randomized into the following groups: Control,
      osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose
      resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol
      treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used
      to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels.
      Western blotting was performed to assess the protein expression of sirtuin 1
      (SIRT1), nuclear factor (NF)-kappaB and NF-kappaB inhibitor (IkB) alpha. In the
      present study, the results indicated that resveratrol markedly improved the bone
      mineral density value, femoral porosity and bone mechanical tests in osteoporosis
      rats. Administration of resveratrol significantly decreased the serum levels of
      ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol
      significantly promoted the protein expression of SIRT1, suppressed NF-kappaB and
      activated the IkBalpha protein expression in rats with osteoporosis. In
      conclusion, treatment with resveratrol significantly improved the final body
      weight of the osteoporosis rats via the SIRT1-NF-kappaB signaling pathway. The
      present study suggested that resveratrol exerted a protective effect on
      osteoporosis through activation of the SIRT1-NF-kappaB signaling pathway in rats.

PMID- 29201211
TI  - Effects of freshwater clam extract on fracture induced inflammation at early
      stage.
AB  - The inflammatory process after traumatic fracture and soft tissue injury includes
      release of inflammatory cytokines and activated polymorph nuclear cells (PMN)
      that can cause subsequent affected limbs delayed healing and vital organ
      complications. Analgesics have good effect on relief of the symptom but may cause
      further burden for hepatic and renal metabolism. Freshwater clam extract (FCE)
      has been demonstrated to suppress the release of the pro-inflammatory cytokine
      tumor necrosis factor-alpha production after hemorrhagic shock, and decrease the
      level of liver injury marker in rats. The aim of the present study was to
      determine whether FCE is able to affect the inflammation induced by unilateral
      tibial fracture in a rat model. The rats were randomly divided into control,
      fracture, FCE and fracture with FCE groups. The fracture group received left
      tibia and fibula shaft fractures using a consistent three point bending method.
      For the fracture with FCE group, FCE (40 mg/kg) was administered orally after
      fracture. Their physiological changes were continuously monitored for 48 h. Blood
      samples were extracted from the femoral arterial catheter at 1, 3, 6, 9, 12, 18,
      24 and 48 h after fracture. In comparison with fracture group, those whom were
      fed with FCE had more stable heart rate frequency, lower central temperature at
      the initial h, and lower serum level of the proinflammatory cytokines and muscle
      damage markers induced by fracture. FCE was also associated with decreased
      recruitment of inflammatory cells in the adjacent soft tissue. Thus, the present
      results suggest that FCE could decrease fracture induced inflammation reaction
      and have beneficial regulatory effect on post inflammatory response.

PMID- 29201212
TI  - Anti-aging effect of fullerenol on skin aging through derived stem cells in a
      mouse model.
AB  - Fullerenol is similar to graphite in terms of structure. In the present study,
      the anti-aging effect of fullerenol on skin through derived stem cells in a mouse
      model was assessed and the potential mechanism of fullerenol was investigated.
      The anti-aging effect of fullerenol effectively inhibited the retention rate of
      transplanted adipose-derived stem cells and increased the thickness of the dermal
      portion of skin and collagen ratio in mice. The effect of fullerenol on the
      proliferation of stem cells was observed. Treatment with fullerenol effectively
      promoted the mRNA expression of Runt-related transcription factor 2, alkaline
      phosphatase and osteocalcin in a mouse model of skin aging induced by D
      galactose. However, fullerenol treatment effectively suppressed the protein
      expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and
      increased forkhead box protein O1 (FoxO1) protein expression in the mice model of
      skin aging induced by D-galactose. These results demonstrate that the anti-aging
      effect of fullerenol on skin through derived stem cells may be mediated in mice
      via the PPAR-gamma/FoxO1 signaling pathway.

PMID- 29201213
TI  - Protective role of tenuigenin on sepsis-induced acute kidney injury in mice.
AB  - Acute kidney injury (AKI) is a severe complication of sepsis, which largely
      contributes to the associated high mortality rate. Tenuigenin (TNG) is a natural
      product isolated from Polygala tenuifolia root, which possesses anti-inflammatory
      and anti-oxidant properties. The present study investigated the effects of TNG on
      sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP). TNG
      was demonstrated to alleviate sepsis-induced AKI by reducing pathological changes
      and significantly decreasing the levels of blood urea nitrogen, serum creatinine
      and kidney coefficient. The production of inflammatory cytokines, including tumor
      necrosis factor alpha and interleukin-6, was markedly inhibited by TNG.
      Hematoxylin-eosin staining revealed that the morphological changes of kidney
      tissues in CLP mice were reversed following TNG treatment. Furthermore, treatment
      with TNG inhibited the production of nitric oxide and prostaglandin E2. Finally,
      TNG inhibited the activation of the nuclear factor-kappaB (NF-kappaB) signaling
      pathway. The present study suggested that TNG alleviates sepsis-induced AKI by
      inhibiting the NF-kappaB signaling pathway, which provides a novel approach for
      treating sepsis-induced AKI.

PMID- 29201214
TI  - Sirt1 regulates apoptosis and extracellular matrix degradation in resveratrol
      treated osteoarthritis chondrocytes via the Wnt/beta-catenin signaling pathways.
AB  - Osteoarthritis (OA) has become a major public health problem with the increased
      aging population. Previous studies have demonstrated that resveratrol (RES) was
      able to increase the level of sirtuin 1 (Sirt1) in OA chondrocytes. However,
      further investigations are required to elucidate the precise molecular mechanism
      of RES and the potential link between Sirt1 and RES. Therefore, the present study
      used 30 clinical OA chondrocyte to examine chondrocyte viability, apoptosis rate
      and the mRNA and protein expression levels of Sirt1 and relevant genes implicated
      in apoptosis, extracellular matrix (ECM) degradation and Wnt/beta-catenin
      signaling pathway. RES and nicotinamide were used as the stimulus and inhibitor,
      respectively. The results demonstrated that the apoptotic rate reduced as the
      cell population decreased from 13.83 to 6.55% in response to 10 uM RES.
      Expression levels of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax),
      procaspase-3 and -9, matrix metalloproteinase 1 (MMP1), MMP3, MMP13, Wnt3a,
      Wnt5a, Wnt7a and beta-catenin were significantly inhibited (P<0.01), whereas the
      level of Bcl-2 was significantly increased (P<0.01) in OA chondrocytes treated
      with 10 uM RES. These observations suggested that Sirt1 may regulate apoptosis
      and ECM degradation in RES-treated osteoarthritis chondrocytes via the Wnt/beta
      catenin signaling pathway.

PMID- 29201215
TI  - Contrast-enhanced computerized tomography combined with a targeted nanoparticle
      contrast agent for screening for early-phase non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a major cause of morbidity and mortality,
      and patients with NSCLC are frequently diagnosed at an advanced stage. This is
      primarily due to a lack of advanced and sensitive protocols for the detection of
      early stage NSCLC. Therefore, methods for the accurate diagnosis of early stage
      NSCLC are urgently required to improve survival rates. The present study
      investigated the use of contrast-enhanced computerized tomography (CECT) combined
      with a targeted nanoparticle contrast agent (TNCA) to diagnose early-stage NSCLC
      in a mice xenograft model. The TNCA used was lenvatinib, a multi-target tyrosine
      kinase inhibitor that inhibits vascular endothelial growth factor receptor 1-3,
      fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor
      beta, proto-oncogene tyrosine-protein kinase receptor Ret and mast/stem cell
      growth factor receptor Kit. Xenograft NSCLC mice were established and used to
      analyze the efficacy of CECT-TNCA compared with CT scanning alone. The TNCA was
      inhaled with the use of an atomizer. The results demonstrated that CECT-TNCA
      improved the sensitivity of the diagnosis of early stage NSCLC. In addition,
      imaging using the TNCA enabled the visualization of nodules in the lung in mice
      with early stage NSCLC. In addition, lung nodule signal enhancement was increased
      in CECT-TNCA compared with CT, suggesting a high accurate accumulation of the
      TNCA in tumor nodules. Mice diagnosed with early stage NSCLC exhibited a higher
      eradication rate of NSCLC after treatment with cisplatin compared with mice with
      advanced stage NSCLC. These data indicate that the sensitivity and accuracy of CT
      imaging for the diagnosis of early stage NSCLC was improved through combination
      with the liposome-encapsulated TNCA.

PMID- 29201216
TI  - Role of microRNA-26a in the diagnosis of lower extremity deep vein thrombosis in
      patients with bone trauma.
AB  - The present study aimed to investigate the role and mechanism of action of
      microRNA (miR)-26a in deep vein thrombosis (DVT). Peripheral blood was collected
      from 45 patients with DVT and 40 healthy controls. Levels of miR-26a, chemokine C
      C motif ligand (CCL)2 mRNA and CCL7 mRNA were detected using reverse
      transcription-quantitative polymerase chain reaction and the value of miR-26a in
      the clinical diagnosis of DVT was assessed using receiver operating
      characteristic curve analysis. The correlation of miR-26a with CCL2 and CCL7
      levels was analyzed using Spearman's rank correlation. In addition, miR-26a and
      protein kinase C delta (PRKCD) were overexpressed in human umbilical vein
      endothelial cells (HUVECs) and PRKCD expression was knocked down by small
      interfering (si)RNA. Western blotting was conducted to detect the expression of
      PRKCD and p65. Furthermore, a dual-luciferase reporter gene assay was performed.
      The results of the current study demonstrated that the expression of miR-26a was
      significantly downregulated in the peripheral blood of patients with DVT compared
      with healthy controls (P<0.05) and negatively correlated with CCL2 and CCL7
      levels (P<0.05). Furthermore, it was demonstrated that miR-26a markedly inhibited
      the expression of PRKCD, significantly decreased levels of CCL2 and CCL7 mRNA
      (P<0.05) and inhibited activation of the NF-kappaB signaling pathway.
      Overexpression of PRKCD in HUVECs inhibited the effects of miR-26a and markedly
      upregulated the phosphorylation of p65. The present study indicated that miR-26a
      directly targets PRKCD mRNA and that miR-26a may be a useful biomarker in the
      clinical diagnosis of DVT. Thus, the present findings suggest that miR-26a
      regulates the NF-kappaB signaling pathway by binding to PRKCD mRNA, inhibits the
      expression of CCL2 and CCL7 and reduces the risk of DVT.

PMID- 29201217
TI  - Curcumin inhibits the development of non-small cell lung cancer by inhibiting
      autophagy and apoptosis.
AB  - Among patients with primary lung cancer, 75-80% present with non-small cell lung
      cancer (NSCLC). However, there is a lack of studies into the potential preventive
      effects of curcumin against the activation of autophagy in NSCLC. Therefore, the
      present study primarily focused on the protective role of curcumin in NSCLC. It
      was demonstrated that curcumin decreased the viability of the human lung cancer
      cells lines, A549 and H1299, in a time-and dose-dependent manner (P<0.05).
      Treatment with curcumin also suppressed the colony formation capacities of A549
      and H1299 cells. Following incubation with 10 uM curcumin for 48 h, cell
      apoptosis was significantly increased by 2.35- and 3.02-fold in A549 and H1299
      cells, respectively, when compared with controls (P<0.01). Furthermore, curcumin
      treatment markedly increased the number and volume of autophagosomes in A549 and
      H1299 cells when compared with controls. Treatment with 10 uM curcumin for 48 h
      also significantly reduced the phosphorylation levels of mechanistic target of
      rapamycin (mTOR), ribosomal protein S6, phosphoinositide 3-kinase and AKT
      (protein kinase B) in A549 and H1299 cells (P<0.05). These data indicated that
      curcumin enhanced autophagy and apoptosis in NSCLC cells by acting as an mTOR
      complex1/2 inhibitor.

PMID- 29201218
TI  - SVP-B5 peptide from Buthus martensii Karsch scorpion venom exerts
      hyperproliferative effects on irradiated hematopoietic cells.
AB  - Previous studies have demonstrated the radioprotective efficacy of scorpion venom
      peptide, fraction II (SVPII) from the venom of Buthus martensii Karsch. In the
      present study, the SVP-B5 polypeptide, which is one of the active components of
      SVPII, was purified using a two-step chromatographic process. SVP-B5
      significantly promoted the proliferation of irradiated M-NFS-60 mouse-derived
      myelocytic leukemia cells. In addition, SVP-B5 effectively and persistently
      promoted hematopoietic recovery and expansion of hematopoietic cells after
      irradiation as demonstrated by cobblestone area forming cell and long-term bone
      marrow culture assays. Treatment of M-NFS-60 cells with SVP-B5 upregulated the
      expression of interleukin 3 receptor and activated the Janus kinase-2/signal
      transducer and activator of transcription 5 signaling pathway. In conclusion, the
      present study demonstrated that SVP-B5 has growth factor-like properties and may
      be used as a therapeutic modality in the recovery of severe myelosuppression,
      which is a common side effect of radiotherapy.

PMID- 29201219
TI  - Blockade of 146b-5p promotes inflammation in atherosclerosis-associated foam cell
      formation by targeting TRAF6.
AB  - Atherosclerosis (AS) is a chronic inflammation in response to lipid accumulation.
      Increasing evidence has demonstrated that numerous microRNAs (miRs) have critical
      roles in inflammatory responses. A previous study suggested that miR-146b-5p is
      possibly associated with AS; however, its exact role has remained largely
      elusive. The present study aimed to investigate the potential role of miR-146b-5p
      in AS and to explore the underlying mechanism. Fist, the levels of miR-146b-5p
      were determined in foam cells and clinical specimens from patients with AS by
      reverse-transcription quantitative PCR. The role of miR-146b-5p in AS was then
      investigated by using miR-146b-5p inhibitor. The results demonstrated that the
      expression levels of miR-146b-5p were elevated in the lesions of patients with
      AS. In addition, the levels of miR-146b-5p in THP-1 cells stimulated with phorbol
      12-myristate 13-acetate (100 nM) to induce their differentiation into macrophages
      were dose- and time-dependently elevated by oxidized low-density lipoprotein
      treatment applied for inducing foam cell formation. miR-146b-5p was also revealed
      to directly target tumor necrosis factor receptor-associated factor 6 (TRAF6),
      which functions as a signal transducer in the nuclear factor-kappaB (NF-kappaB)
      pathway. Furthermore, the present study reported for the first time that miR-146b
      5p inhibition promotes the inflammatory response and enhances lipid uptake during
      foam cell formation. In conclusion, miR-146b-5p inhibition promoted chronic
      inflammation and had a detrimental role during AS-associated foam cell formation
      by targeting TRAF6.

PMID- 29201220
TI  - Rigid laryngoscope manifestations of 61 cases of modern laryngeal tuberculosis.
AB  - The present study investigated the clinical characteristics and diagnosis of
      modern laryngeal tuberculosis (TB). A total of 61 patients that were
      pathologically diagnosed with laryngeal TB between 1998 and 2012 were
      retrospectively analyzed using laryngoscopy methods. The primary symptoms of
      laryngeal TB observed in the present study include hoarseness and sore throat,
      and in the majority of cases, laryngeal TB was not associated with pulmonary TB
      (ratio 41/61, 67.2%). Systemic symptoms included low-grade fever and night
      sweats, which were rarely observed (20/61, 32.8%). Laryngoscopy results were
      summarized into 3 types: Edema type (24 cases), proliferation type (34 cases) and
      ulcer exudation type (3 cases). The positive rate of purified protein derivative
      (PPD) examination was 86.9%, which was 63.9% for sputum bacterium analysis.
      Pathological analysis indicated that there were a large number of phagocytes and
      giant cell reactions, stroma hyperplasia of epithelioid cells, and the Langhans
      cells constituted of granuloma and necrotic tissue, with caseous necrosis as a
      typical manifestation. Modern laryngeal TB is characterized by severe local
      symptoms like hoarseness and sore throat and mild systemic symptoms like fever
      and night sweat, and the diagnosis is based on patient history, laryngoscopy
      analysis, and PPD and sputum bacteria examinations used in combination. However,
      pathological biopsies and acid-fast bacilli examinations are required for the
      final diagnosis.

PMID- 29201221
TI  - Leptin upregulates COX-2 and its downstream products in aortic endothelial cells.
AB  - The adipocyte-derived hormone leptin is associated with hypertension. The
      involvement of cyclooxygenase-2 (COX-2) and its downstream vasomotor products
      prostaglandin (PG) and thromboxane (TX)A2 in the mechanisms of action of leptin
      have remained elusive. The aim of the present study was to investigate the
      effects of leptin on the expression of COX-2 by rat aortic endothelial cells
      (RAECs) and the concentration of its products, represented by 6-keto PGF1alpha
      and TXB2, in the culture media. RAECs were isolated, cultured and identified by
      immunofluorescence staining. The RAECs were incubated with different
      concentrations of leptin (10-10, 10-9 and 10-8 M) for various durations (36 or 48
      h). COX-2 mRNA and protein expression in the cells was detected by reverse
      transcription quantitative PCR and western blot analysis, respectively. The
      vasodilator 6-keto PGF1alpha and the vasoconstrictor TXB2 were detected in the
      supernatant by ELISA. The cultured cells displayed specific factor VIII
      expression in the cytoplasm. Compared with the PBS-treated control group, leptin
      significantly increased the expression of COX-2 mRNA and protein in a time- and
      dose-dependent manner (P<0.01). Furthermore, the vasodilator 6-keto PGF1alpha was
      increased and the TXB2/6-keto PGF1alpha ratio decreased only with relatively high
      concentrations of leptin (10-9 or 10-8 M; P<0.01), but TXB2 levels were not
      affected (P>0.05). In conclusion, leptin significantly increased the expression
      of inflammatory marker COX-2 and its downstream product 6-keto PGF1alpha, while
      also decreasing the TXB2/6-keto PGF1alpha ratio in vitro. These observations
      suggested that COX-2 may have an important role in the effects of leptin on
      inflammation, such as the low-inflammatory disease hypertension. However,
      selective COX-2 inhibitors may increase the risk of hypertension due to
      inhibiting 6-keto PGF1alpha, the vasodilator product of COX-2.

PMID- 29201222
TI  - Contrast-enhanced ultrasound is better than magnetic resonance imaging in
      evaluating the short-term results of microwave ablation treatment of uterine
      fibroids.
AB  - Contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) were
      compared in evaluating the short-term effects of microwave ablation (MWA) on
      uterine fibroids. A total of 60 patients with uterine fibroids treated by MWA
      were enrolled in the experimental group during their two-year follow-up period
      according to the inclusion criteria. Conventional two-dimensional US, MRI and
      CEUS were performed to determine the volume reduction and the fibroid residue by
      displaying the size, echo and signal intensity of fibroids prior to and after MWA
      treatment. As the control group, 60 consecutive patients were recruited on their
      follow-up visit at least two years after MWA treatment of uterine fibroids.
      Significant differences were observed in the wash-in rate (WiR) of the fibroid
      tissue, start time difference, rise time ratio (RTR) and WiR ratio between the
      experimental and control groups (P<0.05). However, the WiR of fibroid vessel,
      total area under the curve of fibroid vessel and tissue, and rise time difference
      (RTD) between fibroid vessel and tissue did not display any significant
      differences between the two groups. Fibroids were either reduced in volume or
      cured by MWA therapy in patients with uterine fibroids. The reductions in volume
      of hypointense, isointense and hyperintense fibroids were 62.42+/-18.13, 53.27+/
      10.05 and 47.43+/-9.56%, respectively, on T1-weighted imaging (T1WI). On T2WI,
      the corresponding reductions were 67.32+/-32.63, 59.36+/-19.36 and 42.63+/
      10.37%, respectively. The higher the signal intensity on T1WI and T2WI, the lower
      the reduction in volume. It is indicative that different blood supply to fibroids
      results in different ablation. CEUS was proved to be more effective than MRI in
      evaluating the effects of MWA on uterine fibroids during the first postoperative
      year.

PMID- 29201223
TI  - Application of positron emission tomography-computed tomography in the diagnosis
      of pulmonary ground-glass nodules.
AB  - The aim of the present study was to investigate the value of positron emission
      tomography-computed tomography (PET-CT) using 18F-fluorodeoxyglucose in the
      clinical diagnosis of pulmonary ground-glass nodule. In total, 54 patients with
      pulmonary GGN that were identified by PET-CT examination were selected and
      confirmed by pathology and clinical diagnosis in hospital between April 2014 and
      April 2015. The association between PET-CT findings and pathology, and the value
      of PET-CT were then evaluated. In the 54 patients, solitary pulmonary GGN with a
      nodule diameter of between 0.6 and 2.0 cm were detected. Amongst them, the PET-CT
      examination of 42 patients revealed hyper metabolic nodules, and were all mixed
      GGN type nodules with a diameter >1 cm. The PET-CT examination of the remaining
      12 patients demonstrated no evidence of metabolic abnormalities and the nodules
      in these patients were pure or mixed GGN with a diameter <1 cm (except 2 cases
      with a diameter >=1 cm). Furthermore, the diagnoses for all patients were
      pathologically confirmed by CT-guided needle biopsy or thoracoscopic surgical
      resection. Amongst them, there were 41 cases of lung adenocarcinoma, 4 cases of
      fungal infection, 7 cases of inflammation and 2 cases of adenomatoid hyperplasia.
      Additionally, PET-CT has a lower detection rate for smaller GGN exhibits no clear
      advantage for pure GGN, but has a higher detection rate for larger GGN. In
      conclusion, to a certain extent, PET-CT makes up for the shortcomings of
      traditional imaging and has some clinical value for the diagnosis of GGN.

PMID- 29201224
TI  - Expression of NF-E2-related factor 2 in a rat dural arteriovenous fistula model.
AB  - Intracranial dural arteriovenous fistulas (DAVFs) are complex intracranial
      vascular malformations that may lead to hemorrhage. Although the precise
      mechanisms by which DAVFs occur remain unknown, dural angiogenesis may be a vital
      factor in its pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2)
      significantly influences angiogenesis; however, the association between DAVF and
      Nrf2 remains unclear. Therefore, the present study investigated whether DAVF
      alters the expression of Nrf2 in an experimental animal model of DAVF. The DAVF
      group underwent surgery of the left common carotid artery-external jugular vein
      anastomosis, cauterization of the vein draining transverse sinus and thrombosis
      of the sagittal sinus to induce venous hypertension (VH). At 1, 4 and 7 days post
      surgery, rats were sacrificed to collect brain samples. Western blot analysis,
      immunofluorescence staining and reverse transcription-quantitative polymerase
      chain reaction were used to determine whether DAVF activated the Nrf2 signaling
      pathway. The results demonstrated that the expression of Nrf2 mRNA and protein,
      and the expression of its downstream genes heme oxygenase-1 and NAD(P)H: quinine
      oxidoreductase-1 significantly increased 1 day after surgery. The expression of
      these genes decreased but remained high 4 days following surgery and only
      returned to baseline 7 days after surgery. Compared with the sham-surgery and
      control groups, DAVF-induced brain edema reached a peak 1 day following DAVF
      surgery and only returned to normal levels 7 days post-surgery. Taken together,
      these data indicate the potential contribution of Nrf2 to the formation of DAVFs
      and suggest that VH may induce the upregulation of Nrf2.

PMID- 29201226
TI  - Bronchial damage and diffuse alveolar hemorrhage following chlorine gas
      inhalation: A case report.
AB  - Chlorine is a toxic inhalant and sources of exposure for individuals include
      accidental releases of chlorine vapor due to industrial or chemical
      transportation accidents. Inhalation of a large quantity of gas may cause
      circulatory and respiratory disorders or even mortality; however, the effects of
      a small amount of chlorine gas may be asymptomatic. The present case study
      presents a successfully treated 55-year-old male patient exposed to chlorine gas,
      resulting in bronchial damage and diffuse alveolar hemorrhage. Endobronchial and
      alveolar injuries were evaluated by direct observation using fiberoptic
      bronchoscopy (FB) and analyzing bronchoalveolar lavage fluid obtained by FB.
      Taking a precise medical history from the patient is crucial to correctly
      diagnose toxic gas inhalation. In addition, a timely and proper evaluation with
      chest imaging as well as FB may provide useful clinical information. Therefore,
      clinicians should consider performing FB if the circumstances permit.

PMID- 29201225
TI  - Long non-coding RNA ANRIL promotes the proliferation, migration and invasion of
      human osteosarcoma cells.
AB  - The long antisense non-coding RNA ANRIL is 3.8 kb in length and serves an
      important role in the tumorigenesis and progression of a number of malignancies.
      However, its function in human osteosarcoma remains unknown. The present study
      investigated the role of ANRIL in human osteosarcoma cell lines and clinical
      tumor samples. The expression of ANRIL was analyzed in 19 osteosarcoma and paired
      adjacent non-cancerous tissues using reverse transcription-quantitative
      polymerase chain reaction. Knockdown of ANRIL expression using lentivirus
      mediated small interfering RNA was performed to investigate the role of ANRIL in
      tumor proliferation and metastasis using MTT, colony formation and transwell
      assays. The results demonstrated that ANRIL expression was upregulated in
      osteosarcoma tissues when compared with ANCT samples. In addition, knockdown of
      ANRIL expression in vitro reduced cell proliferation and invasion. These results
      indicated that ANRIL is upregulated in osteosarcoma tissues, and may promote the
      proliferation and metastasis of osteosarcoma cells. Therefore, ANRIL may serve as
      a novel biomarker and target of novel therapies for the treatment of patients
      with osteosarcoma.

PMID- 29201227
TI  - Oridonin enhances in vitro anticancer effects of lentinan in SMMC-7721 human
      hepatoma cells through apoptotic genes.
AB  - The aim of the present study was to determine the ability of oridonin to enhance
      the anticancer activity of lentinan (LNT) in SMMC-7721 human hepatoma cells in
      vitro by using various techniques, including MTT, flow cytometry, quantitative
      PCR and western blot assays. The results demonstrated that 20 ug/ml was a non
      toxic concentration of oridonin for L02 normal liver cells and SMMC-7721 cells,
      while 0-200 ug/ml of LNT only had anti-proliferative effects on SMMC-7721 cells.
      LNT at 100 and 200 ug/ml inhibited the growth of SMMC-7721 cells by 22.8 and
      60.0%, respectively, and after addition of 20 ug/ml oridonin, the inhibitory rate
      of 100 and 200 ug/ml LNT was increased to 47.2 and 80.7%, respectively. Oridonin
      (20 ug/ml) + LNT (200 ug/ml)-treated SMMC-7721 cells showed the highest apoptotic
      rate, which was 40.5+/-2.5%, which was higher than that of cells treated with LNT
      only. LNT raised the mRNA and protein expression of caspase-3, -8 and -9 as well
      as B-cell lymphoma 2 (Bcl-2)-associated X protein, p53 and p21, while reducing
      the expression of Bcl-2, Bcl extra large protein, epidermal growth factor (EGF)
      and EGF receptor expression in SMMC-7721 cells as compared to that in control
      cells. Treatment with 20 ug/ml oridonin and 200 ug/ml LNT increased these changes
      of gene expression. From the obtained results, it may be concluded that oridonin
      raised the in vitro anti-cancer effects of LNT in SMMC-7721 cells. Oridonin may
      also be used as a sensitizing agent to increase the anticancer activity of LNT in
      vivo.

PMID- 29201228
TI  - Insect tea attenuates hydrochloric acid and ethanol-induced mice acute gastric
      injury.
AB  - The aim of the present study was to investigate the protective effect of insect
      tea on HCl/ethanol-induced gastric ulcers in ICR mice. The serum levels of
      vasoactive intestinal peptide, substance P, somatostatin, motilin and endothelin
      1 in mice were assessed using commercial kits and gastric tissues of superoxide
      dismutase (SOD, nitric oxide (NO) and malondialdehyde (MDA) were determined using
      western blot analysis Insect tea significantly reduced HCl/ethanol-induced
      gastric juice secretion and increased the pH of gastric juice (P<0.05). Insect
      tea treatment signfiicantly increased vasoactive intestinal peptide and
      somatostatin, and significantly decreased motilin, substance P and endothelin
      levels in the serum (P<0.05). Treatment with insect tea was demonstrated to
      significantly increase levels of gastric SOD and NO and to reduce levels of MDA
      in the gastric ulcer mouse model (P<0.05). The gastric expression of inhibitor of
      nuclear factor-kappaB (NF-kappaB), epidermal growth factor (EGF), EGF receptor,
      neuronal nitric oxide synthase (nNOS), endothelial NOS, Mn-SOD, Cu/Zn-SOD and
      catalase was significantly increased in mice treated with inset tea compared with
      untreated model mice (P<0.05). Levels of NF-kappaB, and inducible NOS were
      demonstrated to be decreased in mice treated with insect tea compared with
      untreated model mice (P<0.05). The results of the present study suggest that
      insect tea has a protective effect against HCl/ethanol-induced gastric ulcers in
      ICR mice. This effect may be achieved via modulating serum neuropeptide levels,
      reducing gastric juice secretion, and modulating the inflammation- and
      antioxidant-associated protein expressions in gastric tissue.

PMID- 29201229
TI  - Antimicrobial resistance and prevalence of CvfB, SEK and SEQ genes among
      Staphylococcus aureus isolates from paediatric patients with bloodstream
      infections.
AB  - Staphylococcus aureus (S. aureus) is one of the most frequently isolated
      pathogens in neonatal cases of early and late-onset sepsis. Drug resistance
      profiles and carriage of toxin genes may affect the treatment and outcome of an
      infection. The present study aimed to determine the antimicrobial resistance
      patterns and frequencies of the toxin-associated genes conserved virulence factor
      B (CvfB), staphylococcal enterotoxin Q (SEQ) and staphylococcal enterotoxin K
      (SEK) among S. aureus isolates recovered from paediatric patients with
      bloodstream infections (BSIs) in Guangzhou (China). Of the 53 isolates, 43.4%
      were methicillin-resistant S. aureus (MRSA), and resistance rates to penicillin,
      erythromycin, clindamycin, trimethoprim/sulfamethoxazole, tetracycline, and
      ciprofloxacin of 92.5, 66.0, 62.3, 13.2, 20.8 and 1.9% were recorded,
      respectively. However, no resistance to nitrofurantoin,
      dalfopristin/quinupristin, rifampicin, gentamicin, linezolid or vancomycin was
      detected. Resistance to erythromycin, clindamycin and tetracycline in the MRSA
      group was significantly higher than that in the methicillin-susceptible S. aureus
      (MSSA) group. No significant differences in antimicrobial resistance patterns
      were noted between two age groups (<=1 year and >1 year). The proportion of S.
      aureus isolates positive for CvfB, SEQ and SEK was 100, 34.0 and 35.8%,
      respectively, with 24.5% (13/53) of strains carrying all three genes. Compared
      with those in MSSA isolates, the rates of SEK, SEQ and SEK + SEQ carriage among
      MRSA isolates were significantly higher. Correlations were identified between the
      carriage of SEQ, SEK and SEQ + SEK genes and MRSA (contingency coefficient 0.500,
      0.416, 0.546, respectively; P<0.01). In conclusion, MRSA isolated from the blood
      of paediatric patients with BSIs not only exhibited higher rates of antimicrobial
      resistance than MSSA from the same source, but also more frequently harboured SEK
      and SEQ genes. The combination of the two aspects influenced the dissemination of
      MRSA among children. The present study clarified the characteristics of BSI
      associated S. aureus and enhanced the current understanding of the pathogenicity
      and treatment of MRSA.

PMID- 29201230
TI  - Inhibition of penile tunica albuginea myofibroblasts activity by adipose-derived
      stem cells.
AB  - The activation of tunica albuginea myofibroblasts (MFs) serves an essential role
      in Peyronie's disease (PD). Increasing evidence has reported that adipose tissue
      derived stem cells (ADSCs) have been demonstrated to attenuate the symptoms of PD
      in animal models. However, the mechanisms of the antifibrotic effects of ADSCs in
      PD remain to be fully elucidated. In the present study, the inhibitory effects
      and possible mechanism of ADSCs on the activation of MFs derived from rat penile
      tunica albuginea were investigated. ADSCs were obtained from the paratesticular
      fat of Sprague Dawley rats. MFs were transformed from rat penile tunica albuginea
      fibroblasts through stimulation with 5 ng/ml tumor growth factor-beta1. Transwell
      cell cultures were adopted for co-culture of ADSCs and MFs. Western blot analysis
      was used to assess changes in the expression levels of alpha smooth muscle actin
      (alphaSMA), collagen I, phosphorylated (p)-SMAD family member 2 (Smad2), Smad2,
      ras homolog family member A (RhoA), Rho associated coiled-coil containing protein
      kinase (ROCK)1 and ROCK2, caspase3, caspase9, and matrix metalloproteinases
      (MMPs). Collagen gel assays were used to assess cell contractility. Additionally,
      the concentration of hydroxyproline in the culture medium was detected using
      commercially available kits. It was demonstrated that ADSCs reduced the
      expression of alphaSMA and collagen I of MFs. Furthermore, p-Smad2, RhoA, ROCK1
      and ROCK2 expression was significantly reduced in the MFs+ADSCs group compared
      with that in the MFs-only culture, while the expression of MMPs (MMP2, MMP3, MMP9
      and MMP13) and caspases (caspase3 and caspase9) was upregulated. In addition,
      ADSCs were able to downregulate the concentration of hydroxyproline in the
      culture medium of MFs and reverse the contraction of MFs. Collectively, these
      results suggested that ADSCs inhibited the activation of MFs, decreased collagen
      production, and suppressed the contraction of myofibroblasts, via Smad and
      RhoA/ROCK signaling pathways. Furthermore, ADSCs reduced the deposition of
      collagen and promoted the apoptosis of MFs via MMPs, and caspases. Accordingly,
      the application of ADSCs may provide a novel therapeutic strategy for PD.

PMID- 29201231
TI  - Genetic variation of rs3811463 is associated with gestational diabetes mellitus
      susceptibility.
AB  - Gestational diabetes mellitus (GDM) is a growing health concern, and it increases
      the risk of adverse pregnancy outcomes with substantial long-term adverse health
      impacts on mothers and their offspring. Several studies have revealed specific
      associations between genetic variants and the risk of GDM. Single nucleotide
      polymorphisms (SNPs) are the major type of genetic variation in humans. Let-7
      microRNA targets are enriched for genes containing SNPs associated with glucose
      metabolism, including Lin28. In the present study, the effect of T/C variants of
      rs3811463 (a SNP located near to the let-7 binding site in Lin28) on GDM risk was
      investigated. A GDM rat model was successfully constructed using a high fat diet
      and streptozotocin injection, and the primary skeletal muscle cells were
      isolated. The cell transfection results demonstrated that rs3811463-T/C
      significantly affected the glucose uptake and insulin sensitivity. Reverse
      transcription-quantitative polymerase chain reaction analysis indicated that the
      C allele at rs3811463 regulated the expression of glucose metabolism-associated
      genes insulin-like growth factor two binding protein 2 and glucokinase. Western
      blot analysis data revealed that replacement of the T allele by the C allele at
      rs3811463 modulated the protein level of Sirtuin 1. Taken together, it was
      concluded that the let-7/Lin28 axis regulated glucose uptake and insulin
      sensitivity by modulating the expression of glucose metabolism-associated
      proteins. These findings provide novel evidence on the association between
      genetic variations of rs3811463 and GDM susceptibility.

PMID- 29201232
TI  - Renoprotective effects of emodin against diabetic nephropathy in rat models are
      mediated via PI3K/Akt/GSK-3beta and Bax/caspase-3 signaling pathways.
AB  - Emodin is the main active component of the Chinese medicine rhubarb, which has a
      variety of pharmacological effects and a high clinical value. Its anti
      inflammatory and antitumor effects have been widely studied. The aim of the
      present study was to determine whether emodin has renoprotective effects, and to
      identify the potential underlying mechanisms in a rat model of diabetic
      nephropathy (DN). The changes in mean blood glucose levels, normalized kidney
      weight, urinary albumin excretion, serum creatinine levels and tubulointerstitial
      injury index (TII) scores of the rats with DN were significantly attenuated by
      emodin. Furthermore, treatment with emodin significantly inhibited inflammation
      related factors and oxidative stress, suppressed the expression of intercellular
      adhesion molecule 1 (ICAM-1) and B-cell lymphoma 2-associated X protein (Bax),
      increased phosphorylated Akt and phosphorylated-glycogen synthase kinase 3 (p-GSK
      3beta) expression and inhibited caspase-3 activity in diabetic rats. These data
      suggest that emodin protects against DN and that the underlying mechanism may
      involve the suppression of inflammation, ICAM-1 and Bax, and activation of the
      PI3K/Akt/GSK-3beta pathway.

PMID- 29201233
TI  - Association between connexin 40 and potassium voltage-gated channel subfamily A
      member 5 expression in the atrial myocytes of patients with atrial fibrillation.
AB  - Structural and electrical remodeling within the atrium mediate the pathogenesis
      of atrial fibrillation (AF). Two key genes that sever a role in this remodeling
      are connexin 40 (Cx40) and potassium voltage-gated channel subfamily A member 5
      (KCNA5), respectively. Electrical remodeling is considered to induce structural
      remodeling during AF. In the present study, the left atrial appendage section and
      atrial myocytes of patients with AF were evaluated. It was observed that Cx40 and
      KCNA5 mRNA (P<0.05) and protein (P<0.01) expression was significantly
      downregulated in AF compared with rheumatic heart disease. In addition, a
      positive correlation between the mRNA expression Cx40 and KCNA5 was observed in
      the atrial myocytes of patients with AF (P<0.05; r=0.42). The association between
      Cx40 and KCNA5 expression was subsequently investigated in primary cultured
      atrial myocytes using siRNA transfection. In atrial myocytes, downregulation of
      Cx40 inhibited the expression of KCNA5. Similarly, silencing of KCNA5 suppressed
      the expression of Cx40. These results indicate that synergistic regulation may
      occur between Cx40 and KCNA5 expression. Furthermore, the combined effects of
      electrical and structural remodeling in the atrial myocytes of patients with AF
      may contribute to the pathogenesis of AF.

PMID- 29201234
TI  - Efficacy, safety and influencing factors of intra-calf muscular injection of bone
      marrow mononuclear cells in the treatment of type 2 diabetes mellitus-induced
      lower extremity vascular disease.
AB  - The efficacy, safety and impact of vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) associated with the intra-calf muscular
      injection of bone marrow mononuclear cells (BMMCs) in the treatment of type 2
      diabetes mellitus (T2DM)-induced lower extremity vascular disease (LEVD) were
      evaluated. Patients with T2DM-LEVD were randomly divided into a control group and
      BMMCs group to assess the efficacy and safety of the treatment; serum VEGF and
      bFGF levels were detected. The BMMCs group was divided into superior genicular
      artery (SGA) and inferior genicular artery (IGA) subgroups as well as low-dose
      and high-dose subgroups for the comparison of efficacy indices. The BMMCs group
      exhibited significantly improved indices (P<0.05) compared with the control group
      and no fatalities or cancer occurred. There were no significant changes in serum
      VEGF and bFGF levels (P>0.05). The claudication distance in the IGA subgroup was
      significantly greater that in the SGA subgroup (P<0.05); the low-dose subgroup
      and the high-dose subgroup did not demonstrate any significant differences in
      each index (P>0.05). BMMC treatment for T2DM-LEVD was found to be safe and
      effective and had no significant impact on serum VEGF and bFGF levels in the
      short term; However, the degree of LEVD may affect its efficacy.

PMID- 29201235
TI  - A novel effective chemical hemin for the treatment of acute carbon monoxide
      poisoning in mice.
AB  - There is no effective drug for the therapy of acute carbon monoxide (CO)
      poisoning. The purpose of the present study was to investigate the potential
      preventive and therapeutic effects of hemin on an animal model of acute CO
      poisoning and to provide a potential therapeutic candidate drug. A total of 80
      Kunming mice were randomly divided into four groups, namely the air control,
      acute CO poisoning, hemin-treatment + CO and hemin-pretreatment + CO groups (n=20
      each). Furthermore, the mortality rate of mice, blood carboxyhaemoglobin (HbCO)
      concentration and serum malondialdehyde (MDA) concentration were measured, and
      pathological changes of the hippocampal area were determined using histochemical
      staining. The mice with acute CO poisoning had a 50% mortality rate at 1 h, with
      an increase in blood HbCO, serum MDA levels and pathological impairments of the
      hippocampus. Furthermore, the mortality rate, blood HbCO and serum MDA levels of
      mice with pretreatment and treatment of hemin were decreased. Additionally, the
      pathological changes of the hippocampal area were improved in the hemin-treatment
      and hemin-pretreatment groups compared with the mice treated with CO. These
      results suggest that hemin is a novel effective chemical for the prevention and
      treatment of acute CO poisoning in mice. Therefore, the present study provides a
      novel method and experimental basis for the application of hemin in treating
      patients with acute CO poisoning.

PMID- 29201236
TI  - The role of aplysia ras homolog I in colon cancer cell invasion and adhesion.
AB  - Aplysia ras homolog I (ARHI) acts as a tumor suppressor in certain cancer cells.
      However, the role of ARHI in colon cancer development has not previously been
      reported. The present study aimed to investigate the functional role of ARHI in
      colon cancer focusing on the aspect of metastasis. Furthermore, the molecular
      mechanism underlying its function was explored. The present study detected the
      expression of ARHI in a human colon epithelial cell line and colon cancer cell
      lines using reverse transcription-quantitative polymerase chain reaction and
      western blotting analysis. It was demonstrated that ARHI expression was
      significantly downregulated in colon cancer cell lines compared with the normal
      colon epithelial cell line (P<0.05). An ARHI-pcDNA3.1 plasmid was transfected
      into HCT116 cells to overexpress ARHI. The number of invaded cells and the
      adhesive ability were significantly decreased in the ARHI overexpression group
      compared with the control group, as determined by cell invasion and adhesion
      assays (P<0.05). Furthermore, ARHI overexpression led to increased mRNA and
      protein expression levels of E-cadherin, and decreased mRNA and protein
      expression levels of N-cadherin and vimentin. Wnt/beta-catenin signaling was
      suppressed in HCT116 cells overexpressing ARHI. Lithium chloride, a wnt/beta
      catenin signaling activator, was able to attenuate the effect of ARHI on HCT116
      cell invasion and adhesion. In addition, the effect of ARHI on epithelial
      mesenchymal transition (EMT) in HCT116 cells was reversed by the activation of
      wnt/beta-catenin signaling. In conclusion, the present study provided novel
      evidence that ARHI could inhibit colon cancer cell invasion and adhesion through
      suppressing EMT, and these effects were achieved, at least partially, via the
      suppression of the wnt/beta-catenin signaling pathway. The present findings may
      help in developing novel therapeutic approaches for colon cancer.

PMID- 29201237
TI  - MicroRNA-338-3p targets SOX4 and inhibits cell proliferation and invasion of
      renal cell carcinoma.
AB  - MicroRNA (miR)-338-3p has been reported to be involved in tumor progression and
      development in various types of cancer. However, the biological function of miR
      338-3p and its related molecular pathways involved in the progression of renal
      cell carcinoma (RCC) are unknown. The present study aimed to investigate the
      biological role and underlying mechanism of miR-338-3p in RCC cells. It was
      demonstrated that miR-338-3p expression level was significantly downregulated
      (P<0.05) in RCC tissues and cell lines. Clinical association analysis indicated
      that low expression of miR-338-3p was significantly associated with advanced TNM
      stage and lymph node metastasis (P<0.05). Function assays revealed that
      restoration of miR-338-3p in RCC cells significantly inhibited cell
      proliferation, colony formation, migration and invasion (P<0.05). Notably, sex
      determining region Y-box 4 (SOX4) was identified as a direct target of miR-338-3p
      in RCC cells through a luciferase reporter assay, reverse transcription
      quantitative polymerase chain reaction and western blot analysis. Furthermore,
      SOX4 overexpression partially rescued miR-338-3p-mediated inhibition of cell
      proliferation, colony formation, migration and invasion in RCC cells. These
      results suggested that miR-338-3p functioned as a tumor suppressor in RCC cells
      by modulating SOX4, suggesting that miR-338-3p may have a potential use in the
      treatment of RCC.

PMID- 29201238
TI  - Susceptibility vessel sign predicts poor clinical outcome for acute stroke
      patients untreated by thrombolysis.
AB  - The location and length of the susceptibility vessel sign (SVS) predicts poor
      outcome for patients having received reperfusion therapy. The aim of the present
      study was to assess the predictive value of SVS regarding the clinical outcome
      for patients untreated with thrombolysis. A retrospective study on acute stroke
      patients who underwent multimodal magnetic resonance imaging within 3 days from
      the onset of symptoms was performed. None of the patients had received
      thrombolysis therapy. The presence, location and length of the SVS were assessed.
      Uni- and multivariate analyses were used to examine the association between SVS
      and clinical outcome. A total of 43 SVS+ and 73 SVS- patients were included in
      the study. A modified Rankin Scale (mRS) of <=2 at 3 months was determined in
      41.9% of patients in the SVS+ group and 79.4% in the SVS- group (P<0.001).
      Multivariate analysis revealed that the presence of SVS was an independent
      parameter to predict mRS >2 at 3 months (odds ratio, 3.390; 95% confidence
      interval, 1.122-10.240; P=0.030). For patients with SVS+ status, the location and
      length of the SVS were not independent predictors of the clinical outcome. In
      conclusion, the presence of SVS may predict poor clinical outcome for acute
      stroke patients untreated with thrombolysis.

PMID- 29201239
TI  - ANXA1 affects cell proliferation, invasion and epithelial-mesenchymal transition
      of oral squamous cell carcinoma.
AB  - Annexin A1 (ANXA1) acts either as a tumor suppressor or an oncogene in different
      tumor types. Several clinical studies revealed that the expression of ANXA1 is
      associated with the pathologic differentiation grade in oral squamous cell
      carcinoma (OSCC) patients. However, the direct function of ANXA1 in OSCC
      progression has remained to be fully clarified. The present study was designed to
      investigate the role of ANXA1 in OSCC cell proliferation and invasion in vitro.
      Furthermore, whether ANXA1 was involved in transforming growth factor beta1
      (TGFbeta1)/epidermal growth factor (EGF)-induced epithelial-mesenchymal
      transition (EMT) in OSCC was explored. Tca-8113 and SCC-9 cells were transfected
      with ANXA1-pcDNA3.1 plasmid to overexpress ANXA1. Subsequently, cell
      proliferation and invasion were examined using MTT and Transwell-Matrigel
      invasion assays. TGFbeta1 and EGF were used to induce EMT in Tca-8113 and SCC-9
      cells, and the expression of epithelial (E)-cadherin, neural (N)-cadherin and
      vimentin was determined by western blot analysis. The results demonstrated that
      ANXA1 overexpression induced a significant decrease of cell growth and
      invasiveness in Tca-8113 and SCC-9 cells. The expression of E-cadherin was
      significantly increased, while the expression of vimentin and N-cadherin was
      significantly decreased in ANXA1-overexpressing Tca-8113 and SCC-9 cells. ANXA1
      expression was significantly decreased in TGFbeta1/EGF-treated cells. Furthermore
      TGFbeta1/EGF-induced EMT in OSCC cell lines was attenuated by ANXA1
      overexpression. In conclusion, to the best of our knowledge, the present study
      was the first to evidence that ANXA1 inhibits OSCC cell proliferation and
      invasion in vitro. TGFbeta1/EGF-induced EMT was reversed by ANXA1 in OSCC. ANXA1
      was suggested to be a potential marker for OSCC as well as a novel treatment.

PMID- 29201240
TI  - Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the
      transient receptor potential melastatin 2 channel.
AB  - The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable
      channel activated by cAMP, is expressed on pancreatic beta-cells and is
      responsible for the regulation of insulin secretion. It is known that glucose
      stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1
      (GLP-1), and that the changes in the extracellular glucose concentration alter
      the levels of intracellular adenosine ATP and cAMP. The present study
      hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin
      secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1
      enhanced insulin secretion, indicating the involvement of TRPM2 in this process.
      In addition, the results of current recordings of TRPM2 and measurement of the
      resulting insulin secretion in beta-cells in the presence of GLP-1 and various
      concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2
      channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated
      GLP-1-induced GSIS. By using specific activators or inhibitors, the present study
      demonstrated that the two primary downstream effectors of the GLP-1 receptor,
      exchange protein directly activated by cAMP and protein kinase A, differentially
      influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study
      revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of
      the present study provide a novel avenue for the prevention and treatment of
      diabetes and its complications.

PMID- 29201241
TI  - Clinical value of urinary retinol-binding protein in ascites due to cirrhosis.
AB  - The aim of the present study was to explore the clinical value of urinary retinol
      binding protein (RBP) level in the prognosis of cirrhotic ascites by assessment
      of the RBP levels prior to and following ascites treatment. The levels of urinary
      RBP, urinary microalbumin (mAlb), serum urea nitrogen (urea) and serum creatinine
      (Cr), and the estimated glomerular filtration rate (eGFR) were measured in 90
      patients with cirrhosis and ascites hospitalized in a single institution between
      May 2011 and January 2012, and in 30 healthy controls. The levels of urinary
      mAlb, serum urea and serum Cr were higher in the cirrhotic patients compared with
      the healthy controls (P<0.05). Urinary RBP levels were significantly higher and
      eGFR was significantly lower in the liver cirrhosis group compared with the
      healthy control group (P<0.01). Urinary RBP, urinary mAlb, serum urea and serum
      Cr increased and eGFR decreased as the severity of the ascites increased
      (P<0.05). Urinary RBP was significantly higher in patients whose ascites did not
      respond or was refractory compared with those in whom it subsided (P<0.05),
      exhibiting a gradual increase over time in the former and a gradual reduction
      over time in the latter group (P<0.05). Increased urinary RBP and decreased eGFR
      in the early stage of cirrhosis ascites suggested impaired renal function, which
      serves a role in the process of ascites formation. These results indicated that
      urinary RBP is a sensitive indicator of early renal injury in patients with
      ascites due to cirrhosis and is closely associated with the progression of
      cirrhotic ascites.

PMID- 29201242
TI  - Selective Photooxidation Reactions using Water-Soluble Anthraquinone
      Photocatalysts.
AB  - The aerobic organocatalytic oxidation of alcohols was achieved by using water
      soluble sodium anthraquinone sulfonate. Under visible-light activation, this
      catalyst mediated the aerobic oxidation of alcohols to aldehydes and ketones. The
      photo-oxyfunctionalization of alkanes was also possible under these conditions.

PMID- 29201243
TI  - On the Role of Acidity in Bulk and Nanosheet [T]MFI (T=Al3+, Ga3+, Fe3+, B3+)
      Zeolites in the Methanol-to-Hydrocarbons Reaction.
AB  - The influence of framework substituents (Al3+, Ga3+, Fe3+ and B3+) and morphology
      (bulk vs. nanometer-sized sheets) of MFI zeolites on the acidity and catalytic
      performance in the methanol-to-hydrocarbons (MTH) reaction was investigated. The
      Bronsted acid density and strength decreased in the order
      Al(OH)Si>Ga(OH)Si>Fe(OH)Si?B(OH)Si. Pyridine 15N NMR spectra confirmed the
      differences in the Bronsted and Lewis acid strengths but also provided evidence
      for site heterogeneity in the Bronsted acid sites. Owing to the lower efficiency
      with which tervalent ions can be inserted into the zeolite framework, sheet-like
      zeolites exhibited lower acidity than bulk zeolites. The sheet-like Al-containing
      MFI zeolite exhibited the greatest longevity as a MTH catalyst, outperforming its
      bulk [Al]MFI counterpart. Although the lower acidity of bulk [Ga]MFI led to a
      better catalytic performance than bulk [Al]MFI, the sheet-like [Ga]MFI sample was
      found to be nearly inactive owing to lower and heterogeneous Bronsted acidity.
      All Fe- and B-substituted zeolite samples displayed very low catalytic
      performance owing to their weak acidity. Based on the product distribution, the
      MTH reaction was found to be dominated by the olefins-based catalytic cycle. The
      small contribution of the aromatics-based catalytic cycle was larger for bulk
      zeolite than for sheet-like zeolite, indicating that shorter residence time of
      aromatics can explain the lower tendency toward coking and enhanced catalyst
      longevity.

PMID- 29201244
TI  - Mindfulness-Based Interventions During Pregnancy: a Systematic Review and Meta
      analysis.
AB  - This systematic review aims to assess the effect of mindfulness-based
      interventions carried out during pregnancy exploring mindfulness and mental
      health outcomes. A systematic review was conducted to appraise the current
      literature on the subject area. Inclusion and exclusion criteria were agreed and
      after reviewing titles, abstracts and full papers, 14 articles met the inclusion
      criteria and were included in the review. The quality of included articles was
      checked using the Quality Assessment Tool for Quantitative Studies. Pooled
      results of the randomised controlled trials (RCTs) reporting outcomes on anxiety,
      depression and perceived stress indicated no differences between the mindfulness
      intervention group and the control group. Pooled results of the non-RCTs
      reporting anxiety, depression and perceived stress showed a significant benefit
      for the mindfulness group. Mindfulness as an outcome was assessed in four RCTs
      for which the pooled results show a significant difference in favour of the
      mindfulness intervention when compared to a control group. The pooled results of
      the four non-RCTs also indicate a significant difference following mindfulness
      intervention. Results suggest that mindfulness-based interventions can be
      beneficial for outcomes such as anxiety, depression, perceived stress and levels
      of mindfulness during the perinatal period. Further research would be useful to
      explore if such benefits are sustained during the post-natal period.

PMID- 29201245
TI  - The Relationship Between Adult Attachment Orientation and Mindfulness: a
      Systematic Review and Meta-analysis.
AB  - Mindfulness can be measured as an individual trait, which varies between
      individuals. In recent years, research has investigated the overlap between trait
      mindfulness and attachment. The aim of the present review and meta-analysis was
      to investigate the current evidence linking adult attachment dimensions to trait
      mindfulness dimensions, and to quantitatively synthesize these findings using
      meta-analyses. A systematic literature search was conducted using five scientific
      databases of which, upon review, 33 articles met inclusion criteria. Inclusion
      criteria were peer-reviewed journals and dissertations published in English that
      relied on quantitative methods using reliable and validated self-report measures
      where study participants were aged 16 years and older. Random-effects model meta
      analytic procedures were used to investigate the relationship between both
      constructs. Cross-sectional studies found significant negative correlations
      between adult attachment insecurity, on either dimension (anxiety or avoidance)
      and both total mindfulness score and all five sub-dimensions of mindfulness (act
      with awareness, observe, describe, non-reacting, and non-judging), with the
      exception of a non-significant positive correlation between attachment anxiety
      and observe. The effect size of the relationships ranged from small to medium.
      The overall mean effect sizes were moderate (anxiety, r+ = .34; avoidance, r+ = 
      .28), with both attachment dimensions associated with lower levels of total
      mindfulness. Results are discussed in relation to theory and research.
      Implications for future research include the need to utilize longitudinal design
      to address causality and mechanisms of the relationship between these constructs.

PMID- 29201246
TI  - Differential Effects of Attention-, Compassion-, and Socio-Cognitively Based
      Mental Practices on Self-Reports of Mindfulness and Compassion.
AB  - Research on the effects of mindfulness- and compassion-based interventions is
      flourishing along with self-report scales to assess facets of these broad
      concepts. However, debates remain as to which mental practices are most
      appropriate to develop the attentional, cognitive, and socio-affective facets of
      mindfulness and compassion. One crucial question is whether present-moment,
      attention-focused mindfulness practices are sufficient to induce a cascade of
      changes across the different proposed facets of mindfulness, including
      nonjudgmental acceptance, as well as compassion or whether explicit socio
      affective training is required. Here, we address these questions in the context
      of a 9-month longitudinal study (the ReSource Project) by examining the
      differential effects of three different 3-month mental training modules on
      subscales of mindfulness and compassion questionnaires. The "Presence" module,
      which aimed at cultivating present-moment-focused attention and body awareness,
      led to increases in the observing, nonreacting, and presence subscales, but not
      to increases in acceptance or nonjudging. These latter facets benefitted from
      specific cultivation through the socio-cognitive "Perspective" module and socio
      affective, compassion-based "Affect" module, respectively. These modules also led
      to further increases in scores on the subscales affected by the Presence module.
      Moreover, scores on the compassion scales were uniquely influenced by the Affect
      module. Thus, whereas a present-moment attention-focused training, as implemented
      in many mindfulness-based programs, was indeed able to increase attentional
      facets of mindfulness, only socio-cognitive and compassion-based practices led to
      broad changes in ethical-motivational qualities like a nonjudgmental attitude,
      compassion, and self-compassion.

PMID- 29201247
TI  - Positive Emotion Correlates of Meditation Practice: A Comparison of Mindfulness
      Meditation and Loving-kindness Meditation.
AB  - The purpose of this study was to uncover the day-to-day emotional profiles and
      dose-response relations, both within-persons and between-persons, associated with
      initiating one of two meditation practices, either mindfulness meditation or
      loving-kindness meditation. Data were pooled across two studies of midlife adults
      (N = 339) who were randomized to learn either mindfulness meditation or loving
      kindness meditation in a six-week workshop. The duration and frequency of
      meditation practice was measured daily for nine weeks, commencing with the first
      workshop session. Likewise, positive and negative emotions were also measured
      daily, using the modified Differential Emotions Scale (Fredrickson, 2013).
      Analysis of daily emotion reports over the targeted nine-week period showed
      significant gains in positive emotions and no change in negative emotions,
      regardless of meditation type. Multilevel models also revealed significant dose
      response relations between duration of meditation practice and positive emotions,
      both within-persons and between-persons. Moreover, the within-person dose
      response relation was stronger for loving-kindness meditation than for
      mindfulness meditation. Similar dose-response relations were observed for the
      frequency of meditation practice. In the context of prior research on the mental
      and physical health benefits produced by subtle increases in day-to-day
      experiences of positive emotions, the present research points to evidence-based
      practices - both mindfulness meditation and loving-kindness meditation - that can
      improve emotional wellbeing.

PMID- 29201248
TI  - A Qualitative Study with Healthcare Staff Exploring the Facilitators and Barriers
      to Engaging in a Self-Help Mindfulness-Based Intervention.
AB  - In order to increase the cost-efficiency, availability and ease of accessing and
      delivering mindfulness-based interventions (MBIs), clinical and research interest
      in mindfulness-based self-help (MBSH) interventions has increased in recent
      years. Several studies have shown promising results of effectiveness of MBSH.
      However, like all self-help interventions, dropout rates and disengagement from
      MBSH are high. The current study explored the facilitators and barriers of
      engaging in a MBSH intervention. Semi-structured interviews with members of
      healthcare staff who took part in an MBSH intervention (n = 16) were conducted. A
      thematic analysis approach was used to derive central themes around engagement
      from the interviews. Analyses resulted in four overarching themes characterising
      facilitation and hindrance to engagement in MBSH. These are "attitude towards
      engagement", "intervention characteristics", "process of change" and "perceived
      consequences". Long practices, emerging negative thoughts and becoming self
      critical were identified as the key hindrances, whilst need for stress reduction
      techniques, shorter practices and increased sense of agency over thoughts were
      identified as the key facilitators. Clinical and research implications are
      discussed.

PMID- 29201249
TI  - Socially Inclusive Development: The Foundations for Decent Societies in East and
      Southern Africa.
AB  - This article is concerned with how social processes and social provision are
      conceptualised and measured in societies in order to offer guidance on how to
      improve developmental progress. Significant advances have been made in developing
      multidimensional measures of development, but they provide little guidance to
      governments on how to build sustainable societies. We argue for the need to
      develop a theoretically informed social and policy framework that permits the
      foundations for building decent societies to be put in place by governments. In
      our view the recently developed Decent Society Model provides such a framework.
      Our example is the assessment of government provision, by function, within
      fourteen countries of East and Southern Africa. The context is the current
      debates about socially inclusive development, but we argue that it is necessary
      to range more widely, as social processes of different kinds are multiply
      interrelated. Social inclusion is recognised by governments as well as
      international agencies, including the World Bank and the United Nations, as not
      only an ethical imperative but smart economics; socially inclusive societies are
      more stable and have greater potential for economic growth. Societies that can
      develop sustainably need not only to be inclusive, however, but to provide
      economic security for all, to be socially cohesive and to empower citizens so
      that as individuals and communities they can take control over their own lives.

PMID- 29201250
TI  - Trajectories of Personal Well-Being Attributes Among High School Students in Hong
      Kong.
AB  - How personal well-being of adolescents changes over the high school period is not
      entirely clear in the scientific literature. Using 15 positive youth development
      (PYD) attributes as indicators of well-being, the current study investigated the
      related developmental trajectories among a large sample of Hong Kong adolescents
      from Grade 7 to Grade 12. Individual growth curve modeling revealed that while
      variation existed across different PYD attributes, nine out of 15 positive youth
      development attributes declined in the early adolescence but showed a rebound or
      a slower rate of decline in the late adolescence. The current study serves as a
      pioneering attempt to chart the normative profiles of Chinese adolescents'
      personal well-being over time. The theoretical and practical implications of the
      findings are discussed.

PMID- 29201252
TI  - Social Progress in Spanish Municipalities (2001-2011).
AB  - This paper proposes a methodology for the assessment of social progress in the
      biggest Spanish municipalities between years 2001 and 2011. We follow recent
      descriptions of QoL to elaborate a measurement framework composed of eight
      dimensions, for which 16 subindicators are elaborated from information collected
      using different data sources. Weight constrained Data Envelopment Analysis is
      used to estimate QoL composite indicators in both periods and to compute a
      Malmquist index of social progress, which assesses the evolution of the
      indicators during the decade. The results evidence positive social progress with
      an average improvement of about 5% during the decade. While the Central-Northern
      regions still show the highest levels of QoL, the Southern regions (including the
      islands) dominate the improvement trend. We then decompose the Malmquist index
      into a catching-up effect and a frontier shift effect. Positive catching-up is
      measured in almost all the regions. The worst performing municipalities in 2001
      experienced the largest catching-up effects, a trend that contributes to
      territorial convergence. The frontier shift also shows a positive trend.

PMID- 29201251
TI  - A 4-year Longitudinal Study of Well-being of Chinese University Students in Hong
      Kong.
AB  - The present longitudinal study explored the development of personal well-being in
      university students over 4 years. Personal well-being was indexed by multiple
      indicators including life satisfaction, positive youth development qualities, and
      university engagement. A sample of 434 students enrolled in the new 4-year
      undergraduate program in one university in Hong Kong was successfully followed up
      for 4 years since they started their university study in 2012-2013 academic year.
      Students completed an online survey on a yearly basis and four waves of data were
      collected. Results revealed significant changes in most well-being indicators
      over time with three main observations. First, students' life satisfaction
      remained at a stable level during 4 years. Second, most students' self-reported
      positive youth development competencies followed a U-shaped developmental
      trajectory, which was characterised by a dip in the second year and a continuous
      rebound in the third year and fourth year. Third, students' university engagement
      in different aspects showed significant increments in the third and fourth year
      of university study. The findings underscore the disparate developmental patterns
      of different aspects of student well-being during university study. This suggests
      that there is a need to take into account students' developmental characteristics
      and related challenges in different stages of university life when develop and
      implement programs in university to promote student well-being.

PMID- 29201253
TI  - Gendered Perceptions of Migration Among Ghanaian Children in Transnational Care.
AB  - This study empirically measures the perceptions towards maternal and paternal
      migration of male and female children who stay behind in Ghana. It analyses
      survey data collected in 2010 among secondary school children aged 11-18 in four
      urban areas with high out-migration rates: the greater Accra region, Kumasi,
      Sunyani and Cape Coast (N = 1965). The results show significant gendered
      differences in how children perceive parental migration. Specifically, female
      children have more positive views towards maternal and paternal migration when
      parents are abroad and in a stable marital relationship, when the assessed parent
      is abroad but the other parent is the caregiver in Ghana, when there is a
      frequent change in the care arrangement, and when female children receive
      remittances. These findings were not replicated for male children. The analysis
      highlights the sensitivity of the results to the gender of the child and to the
      characteristics of children's transnational lives that are being analysed.

PMID- 29201254
TI  - Analyzing Gender Differences in the Relationship between Family Influences and
      Adolescent Offending among Boys and Girls.
AB  - The aim of this paper is to examine gender differences in several dimensions of
      family-related variables in the explanation of adolescent offending. Analyses are
      conducted to examine: 1) whether boys and girls differ in levels of offending and
      in levels of family variables respectively, 2) whether the correlations between
      family variables and offending differ by gender, and 3) whether the family
      variables explain gender differences in adolescent offending. The study employs
      self-report data from a sample of young adolescents in Halmstad, Sweden (N =
      889). The findings show that boys offend more than girls and that there are clear
      differences in both levels of the family variables and in the associations
      between the different family variables and offending. The findings also show that
      the family variables cannot explain gender differences in offending. The findings
      in this study are not only relevant theoretically, they also have important
      policy implications.

PMID- 29201255
TI  - English education for healthcare professionals in Japan.
AB  - In a global environment, education for healthcare professionals should include
      cultivating human resources who have the necessary skills to work in an
      international arena. This article will review the current status of English
      education for dental healthcare professionals in Japan. After conducting a
      literature search using the keywords: English education, Japan, and dental, only
      a few studies were found that investigated and proposed suggestions for dental
      professional English education. Even so, these were still in the early stages
      with outcomes yet to be fully evaluated. Even though English is thought
      indispensable for global professionals, and that increasing chances for
      communication skills is necessary, little attention has been addressed to English
      education for dental professionals or the implementation of such education in the
      Japanese undergraduate dental curricula. With the current reality of field
      expansion in dentistry, the need for not only improved English communication
      skills for Japanese dentists, but also the acquisition of essential expertise,
      psychomotor, teambuilding, critical thinking, and creative thinking skills in
      English as well as Japanese, is a definite probability. In order to reach this
      level of knowledge, further efforts and research would be necessary for the
      advancement and development of dental professional English education in Japan.

PMID- 29201256
TI  - Neuropeptides and ATP signaling in the trigeminal ganglion.
AB  - Peripheral nociceptive stimuli from orofacial structures are largely transmitted
      by the trigeminal nerve. According to the peripheral noxious stimuli, neurons in
      the trigeminal ganglion (TG) produce neuropeptides such as substance P, and
      calcitonin-gene-related peptide, etc. Beside the production of neuropeptides,
      there exists unique non-synaptic interaction system between maxillary and
      mandibular neurons in the TG. Neurons in the TG are surrounded by satellite glial
      cells (SGCs), which initially receive the signal from TG neurons. These activated
      SGCs secrete a transmitter to activate adjacent SGCs or TG neurons, thereby
      amplifying the signal, for example, from mandibular neurons to maxillary neurons
      in the TG. Similar to the dorsal root ganglion, in the TG, microglia/macrophage
      like cells (MLCs) are activated by uptake of a transmitter from TG neurons or
      SGCs. This communication between neurons, SGCs, and MLCs results in responses
      such as ectopic pain, hyperesthesia, or allodynia. The focus of this review is
      the cooperative interaction of the maxillary and mandibular nerves in the TG by
      neuropeptides, and adenosine 3'-phosphate (ATP) signaling from neurons to SGCs
      and MLCs. Stimulated neurons either secrete ATP by means of vesicular nucleotide
      transporters, or secrete neuropeptides from the neuronal cell body to mediate
      signal transmission.

PMID- 29201257
TI  - Muscle power during intravenous sedation.
AB  - Intravenous sedation is effective to reduce fear and anxiety in dental treatment.
      It also has been used for behavior modification technique in dental patients with
      special needs. Midazolam and propofol are commonly used for intravenous sedation.
      Although there have been many researches on the effects of midazolam and propofol
      on vital function and the recovery profile, little is known about muscle power.
      This review discusses the effects of intravenous sedation using midazolam and
      propofol on both grip strength and bite force. During light propofol sedation,
      grip strength increases slightly and bite force increases in a dose-dependent
      manner. Grip strength decreases while bite force increases during light midazolam
      sedation, and also during light sedation using a combination of midazolam and
      propofol. Flumazenil did not antagonise the increase in bite force by midazolam.
      These results may suggest following possibilities; (1) Activation of peripheral
      benzodiazepine receptors located within the temporomandibular joint region and
      masticatory muscles may be the cause of increasing bite force. (2) Propofol
      limited the long-latency exteroceptive suppression (ES2) period during jaw
      opening reflex. Thus, control of masticatory muscle contraction, which is thought
      to have a negative feedback effect on excessive bite force, may be depressed by
      propofol.

PMID- 29201258
TI  - Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on
      periodontal diseases.
AB  - Porphyromonas gingivalis (P. gingivalis) is a major oral pathogen and associated
      with periodontal diseases including periodontitis and alveolar bone loss. In this
      review, we indicate that two virulence factors, which are hemoglobin receptor
      protein (HbR) and cysteine proteases "gingipains", expressed by P. gingivalis
      have novel functions on the pathogenicity of P. gingivalis. P. gingivalis
      produces three types of gingipains and concomitantly several adhesin domains.
      Among the adhesin domains, hemoglobin receptor protein (HbR), also called HGP15,
      has the function of induction of interleukin-8 (IL-8) expression in human
      gingival epithelial cells, indicating the possibility that HbR is associated with
      P. gingivalis-induced periodontal inflammation. On bacteria-host cells contact,
      P. gingivalis induces cellular signaling alteration in host cells.
      Phosphatidylinositol 3-kinase (PI3K) and Akt are well known to play a pivotal
      role in various cellular physiological functions including cell survival and
      glucose metabolism in mammalian cells. Recently, we demonstrated that gingipains
      attenuate the activity of PI3K and Akt, which might have a causal influence on
      periodontal diseases by chronic infection to the host cells from the speculation
      of molecular analysis. In this review, we discuss new molecular and biological
      characterization of the virulence factors from P. gingivalis.

PMID- 29201259
TI  - Erratum: Developmental Changes in Mental Rotation: A Dissociation Between Object
      Based and Egocentric Transformations.
AB  - [This corrects the article on p. 67 in vol. 12, PMID: 27512525.].

PMID- 29201260
TI  - Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology
      Assessment Update.
AB  - Background: Retinitis pigmentosa is a group of inherited disorders characterized
      by the degeneration of the photoreceptors in the retina, resulting in progressive
      vision loss. The Argus II system is designed to restore partial functional vision
      in patients with profound vision loss from advanced retinitis pigmentosa. At
      present, it is the only treatment option approved by Health Canada for this
      patient population. In June 2016, Health Quality Ontario published a health
      technology assessment of the Argus II retinal prosthesis system for patients with
      advanced retinitis pigmentosa. Based on that assessment, the Ontario Health
      Technology Advisory Committee recommended against publicly funding the Argus II
      system for this population. It also recommended that Health Quality Ontario re
      evaluate the evidence in 1 year. The objective of this report was to examine new
      evidence published since the 2016 health technology assessment. Methods: We
      completed a health technology assessment, which included an evaluation of
      clinical benefits and harms, value for money, and patient preferences related to
      the Argus II system. We performed a systematic literature search for studies
      published since the 2016 Argus II health technology assessment. We developed a
      Markov decision-analytic model to assess the cost-effectiveness of the Argus II
      system compared with standard care, and we calculated incremental cost
      effectiveness ratios over a 20-year time horizon. We also conducted a five-year
      budget impact analysis. Finally, we interviewed people with retinitis pigmentosa
      about their lived experience with vision loss, and with the Argus II system.
      Results: Four publications from one multicentre international study were included
      in the clinical review. Patients showed significant improvements in visual
      function and functional outcomes with the Argus II system, and these outcomes
      were sustained up to a 5-year follow-up (moderate quality of evidence). The
      safety profile was generally acceptable.In the base case economic analysis, the
      Argus II system was cost-effective compared with standard care if the willingness
      to pay was more than $97,429 per quality-adjusted life-year. We estimated that
      funding the Argus II system would cost the province $0.71 to $0.78 million per
      year over 5 years, assuming 4 implants per year.People with lived experience
      spoke about the challenges of retinitis pigmentosa, including the gradual but
      persistent progression of the disease; its impact on their quality of life and
      their families; and the accessibility challenges they faced. Those who used the
      Argus II system spoke about its positive impact on their quality of life.
      Conclusions: Based on evidence of moderate quality, the Argus II retinal
      prosthesis system improved visual function, real-life functional outcomes, and
      quality of life in patients with advanced retinitis pigmentosa. The Argus II
      system is expensive, but the cost to publicly fund it would be low, because of
      the small number of eligible patients. The Argus II system can only enable
      perception of light/dark and shapes/objects, but these advancements represent
      important gains for people with retinitis pigmentosa in terms of mobility and
      quality of life.

PMID- 29201261
TI  - Electrical Stimulation for Pressure Injuries: A Health Technology Assessment.
AB  - Background: Pressure injuries (bedsores) are common and reduce quality of life.
      They are also costly and difficult to treat. This health technology assessment
      evaluates the effectiveness, cost-effectiveness, budget impact, and lived
      experience of adding electrical stimulation to standard wound care for pressure
      injuries. Methods: We conducted a systematic search for studies published to
      December 7, 2016, limited to randomized and non-randomized controlled trials
      examining the effectiveness of electrical stimulation plus standard wound care
      versus standard wound care alone for patients with pressure injuries. We assessed
      the quality of evidence through Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE). In addition, we conducted an economic
      literature review and a budget impact analysis to assess the cost-effectiveness
      and affordability of electrical stimulation for treatment of pressure ulcers in
      Ontario. Given uncertainties in clinical evidence and resource use, we did not
      conduct a primary economic evaluation. Finally, we conducted qualitative
      interviews with patients and caregivers about their experiences with pressure
      injuries, currently available treatments, and (if applicable) electrical
      stimulation. Results: Nine randomized controlled trials and two non-randomized
      controlled trials were found from the systematic search. There was no significant
      difference in complete pressure injury healing between adjunct electrical
      stimulation and standard wound care. There was a significant difference in wound
      surface area reduction favouring electrical stimulation compared with standard
      wound care.The only study on cost-effectiveness of electrical stimulation was
      partially applicable to the patient population of interest. Therefore, the cost
      effectiveness of electrical stimulation cannot be determined. We estimate that
      the cost of publicly funding electrical stimulation for pressure injuries would
      be $0.77 to $3.85 million yearly for the next 5 years.Patients and caregivers
      reported that pressure injuries were burdensome and reduced their quality of
      life. Patients and caregivers also noted that electrical stimulation seemed to
      reduce the time it took the wounds to heal. Conclusions: While electrical
      stimulation is safe to use (GRADE quality of evidence: high) there is uncertainty
      about whether it improves wound healing (GRADE quality of evidence: low). In
      Ontario, publicly funding electrical stimulation for pressure injuries could
      result in extra costs of $0.77 to $3.85 million yearly for the next 5 years.

PMID- 29201262
TI  - Tobacco Nitrosamine Exposures Contribute to Fetal Alcohol Spectrum Disorder
      Associated Cerebellar Dysgenesis.
AB  - Variability in the phenotypic features and severity of fetal alcohol spectrum
      disorder (FASD) is not fully linked to alcohol dose. We hypothesize that FASD
      type neurodevelopmental abnormalities may be caused by exposures to the tobacco
      specific nitrosamine, NNK, since a high percentage of pregnant women who drink
      also smoke. In vitro experiments using PNET2 human cerebellar neuronal cultures
      examined ethanol and NNK effects on viability and mitochondrial function. Early
      postnatal rat cerebellar slice cultures were used to examine effects of ethanol
      and NNK on cerebellar histology and neuroglial and stress protein expression.
      Ethanol (50 mM) decreased viability and ATP content and increased mitochondrial
      mass, while NNK (100 MUM or higher) selectively inhibited mitochondrial function.
      The slice culture studies demonstrated striking adverse effects of ethanol, NNK
      and ethanol+NNK exposures manifested by architectural disorganization of the
      cortex with relative reductions of internal granule cells, increases in external
      granule cells, and loss of Purkinje cells. Ethanol, NNK, and ethanol+NNK
      inhibited expression of choline acetyltransferase (ChAT) and acetylcholinesterase
      (AChE), and increased levels of 4-hydroxynonenal (HNE). In addition, ethanol
      increased activated Caspase 3, NNK decreased tau and phospho-tau, and ethanol+NNK
      inhibited expression of Aspartyl-beta-hydroxylase (ASPH), which mediates neuronal
      migration. In conclusion, ethanol and NNK were shown to exert independent but
      overlapping adverse effects on cerebellar cortical development, neuronal
      viability, function, and neuroglial protein expression. These findings support
      our hypothesis that NNK exposures via tobacco smoking in pregnancy can contribute
      to FASD-associated neurodevelopmental abnormalities.

PMID- 29201263
TI  - Using social knowledge networking technology to enable meaningful use of
      electronic health record technology in hospitals and health systems.
AB  - Despite the federal policy momentum towards "meaningful use" of Electronic Health
      Records, the healthcare organizational literature remains replete with reports of
      unintended adverse consequences of implementing Electronic Health Records,
      including: increased work for clinicians, unfavorable workflow changes, and
      unexpected changes in communication patterns & practices. In addition to being
      costly and unsafe, these unintended adverse consequences may pose a formidable
      barrier to "meaningful use" of Electronic Health Records. Correspondingly, it is
      essential for hospital administrators to understand and detect the causes of
      unintended adverse consequences, to ensure successful implementation of
      Electronic Health Records. The longstanding Technology-in-Practice framework
      emphasizes the role of human agency in enacting structures of technology use or
      "technologies-in-practice." Given a set of unintended adverse consequences from
      health information technology implementation, this framework could help trace
      them back to specific actions (types of technology-in-practice) and institutional
      conditions (social structures). On the other hand, the more recent Knowledge-in
      Practice framework helps understand how information and communication
      technologies (e.g., social knowledge networking systems) could be implemented
      alongside existing technology systems, to create new social structures, generate
      new knowledge-in-practice, and transform technology-in-practice. Therefore,
      integrating the two literature streams could serve the dual purpose of
      understanding and overcoming unintended adverse consequences of Electronic Health
      Record implementation. This paper seeks to: (1) review the theoretical
      literatures on technology use & implementation, and identify a framework for
      understanding & overcoming unintended adverse consequences of implementing
      Electronic Health Records; (2) outline a broad project proposal to test the
      applicability of the framework in enabling "meaningful use" of Electronic Health
      Records in a healthcare context; and (3) identify strategies for successful
      implementation of Electronic Health Records in hospitals & health systems, based
      on the literature review and application.

PMID- 29201264
TI  - Short or Long End of the Lever? Associations between Provider Communication of
      the "Asthma-Action Plan" and Outpatient Revisits for Pediatric Asthma.
AB  - Background: At the Children's Hospital of Georgia (CHOG), we found that
      outpatient revisits for pediatric asthma were significantly above national norms.
      According to the NIH, costly hospital revisits for asthma can be prevented
      through guidelines-based self-management of asthma, central to which, is the use
      of a written Asthma-Action Plan (AAP). Purpose: The asthma services literature
      has emphasized the role of the healthcare provider in promoting asthma self
      management using the AAP, to prevent hospital revisits. On the other hand, the
      asthma policy literature has emphasized the need for community-based
      interventions to promote asthma self-management. A gap remains in understanding
      the extent of leverage that healthcare providers may have in preventing hospital
      revisits for asthma, through effective communication of AAP in the outpatient
      setting. Our study sought to address this gap. Methods: We conducted a 6-month
      intervention to implement "patient-and-family-centered communication of the AAP"
      in CHOG outpatient clinics, based on the "change-management" theoretical
      framework. Provider communication of AAP was assessed through a survey of "Parent
      Understanding of the Child's AAP." A quasi-experimental approach was used to
      measure outpatient revisits for pediatric asthma, pre- and post-intervention.
      Results: Survey results showed that provider communication of the AAP was
      unanimously perceived highly positively by parents of pediatric asthma patients,
      across various metrics of patient-centered care. However, there were no
      statistically significant differences in outpatient "revisit behavior" for
      pediatric asthma between pre- and post-intervention periods after controlling for
      several demographic variables. Additionally, revisits remained significantly
      above national norms. Conclusions: Results suggest limited potential of
      "effective provider communication of AAP," in reducing outpatient revisits for
      pediatric asthma; and indicate need for broader community-based interventions to
      address patient life variables impacting self-management and hospital revisits
      for pediatric asthma. Findings suggest need for a revised "socio-ecological"
      theoretical framework, and also provide insight into various policy, research,
      and practice implications for asthma management and control.

PMID- 29201265
TI  - 5 Nursing strategies to prevent ventilator-associated pneumonia.

PMID- 29201266
TI  - Band Gap in Magnetite above Verwey Temperature Induced by Symmetry Breaking.
AB  - Magnetite exhibits a famous phase transition, called Verwey transition, at the
      critical temperature TV of about 120 K. Although numerous efforts have been
      devoted to the understanding of this interesting transition, up to now, it is
      still under debate whether a charge ordering and a band gap exist in magnetite
      above TV. Here, we systematically investigate the charge ordering and the
      electronic properties of magnetite in its cubic phase using different methods
      based on density functional theory: DFT+U and hybrid functionals. Our results
      show that, upon releasing the symmetry constraint on the density but not on the
      geometry, charge disproportionation (Fe2+/Fe3+) is observed, resulting in a band
      gap of around 0.2 eV at the Fermi level. This implies that the Verwey transition
      is probably a semiconductor-to-semiconductor transition and that the conductivity
      mechanism above TV is small polaron hopping.

PMID- 29201267
TI  - Electron Beam Irradiation Induced Multiwalled Carbon Nanotubes Fusion inside SEM.
AB  - This paper reported a method of multiwalled carbon nanotubes (MWCNTs) fusion
      inside a scanning electron microscope (SEM). A CNT was picked up by nanorobotics
      manipulator system which was constructed in SEM with 21 DOFs and 1 nm resolution.
      The CNT was picked up and placed on two manipulators. The tensile force was 140
      nN when the CNT was pulled into two parts. Then, two parts of the CNT were
      connected to each other by two manipulators. The adhered force between two parts
      was measured to be about 20 nN. When the two parts of CNT were connected again,
      the contact area was fused by focused electron beam irradiation for 3 minutes.
      The tensile force of the junction was measured to be about 100 nN. However, after
      fusion, the tensile force was five times larger than the tensile force connected
      only by van der Waals force. This force was 70 percent of the tensile force
      before pulling out of CNTs. The results revealed that the electron beam
      irradiation was a promising method for CNT fusion. We hope this technology will
      be applied to nanoelectronics in the near future.

PMID- 29201268
TI  - 3D and 4D Ultrasound: Current Progress and Future Perspectives.
AB  - Purpose of Review: Three-dimensional (3D) echocardiography (3DE) and 4
      dimensional echocardiography (4DE), also known as real-time (RT) 3DE (RT3DE), are
      rapidly emerging technologies which have made significant impact in the clinical
      arena over the years. This review will discuss the recent applications of 3DE in
      diagnosing and treating different types of cardiovascular disease. Recent
      Findings: Recent studies using 3DE expanded on prior findings and introduced
      additional applications to different cardiac conditions. Some studies have used
      3D parameters to prognosticate long-term outcomes. Numerous innovative software
      designs including fully automated algorithms have been introduced to better
      evaluate valvular heart disease and cardiac function. Summary: With further
      evolution of 3DE technologies, this imaging modality will emerge as a powerful
      tool and likely become the imaging modality of choice in the diagnosis and
      management of various cardiac disorders.

PMID- 29201269
TI  - Cardiac Nonmyocyte Cell Functions and Crosstalks in Response to Cardiotoxic
      Drugs.
AB  - The discovery of the molecular mechanisms involved in the cardiac responses to
      anticancer drugs represents the current goal of cardio-oncology research. The
      oxidative stress has a pivotal role in cardiotoxic responses, affecting the
      function of all types of cardiac cells, and their functional crosstalks.
      Generally, cardiomyocytes are the main target of research studies on
      cardiotoxicity, but recently the contribution of the other nonmyocyte cardiac
      cells is becoming of growing interest. This review deals with the role of
      oxidative stress, induced by anticancer drugs, in cardiac nonmyocyte cells
      (fibroblasts, vascular cells, and immune cells). The alterations of functional
      interplays among these cardiac cells are discussed, as well. These interesting
      recent findings increase the knowledge about cardiotoxicity and suggest new
      molecular targets for both diagnosis and therapy.

PMID- 29201270
TI  - Increased Oxidative Damage of RNA in Early-Stage Nephropathy in db/db Mice.
AB  - To evaluate RNA oxidation in the early stage of diabetic nephropathy, we applied
      an accurate method based on isotope dilution high-performance liquid
      chromatography-triple quadruple mass spectrometry to analyze the oxidatively
      generated guanine nucleosides in renal tissue and urine from db/db mice of
      different ages. We further investigated the relationship between these oxidative
      stress markers, microalbumin excretion, and histological changes. We found that
      the levels of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodGuo) were increased in the urine and renal tissue of db/db
      mice and db/db mice with early symptoms of diabetic nephropathy suffered from
      more extensive oxidative damage than lean littermate control db/m mice.
      Importantly, in contrast to the findings in db/m mice, the 8-oxoGuo levels in the
      urine and renal tissue of db/db mice were higher than those of 8-oxodGuo at four
      weeks. These results indicate that RNA oxidation is more apparent than DNA
      oxidation in the early stage of diabetic nephropathy. RNA oxidation may provide
      new insight into the pathogenesis of diabetic nephropathy, and urinary 8-oxoGuo
      may represent a novel, noninvasive, and easily detected biomarker of diabetic
      kidney diseases if further study could clarify its source and confirm these
      results in a large population study.

PMID- 29201271
TI  - Involvement of Mitochondrial Disorders in Septic Cardiomyopathy.
AB  - Sepsis is defined as a life-threatening organ dysfunction caused by a
      dysregulated host response to infection. It remains a leading cause of death
      worldwide, despite the development of various therapeutic strategies. Cardiac
      dysfunction, also referred to as septic cardiomyopathy, is a frequent and well
      described complication of sepsis and associated with worse clinical outcomes.
      Recent research has increased our understanding of the role of mitochondrial
      dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this
      review is to present this evidence as a coherent whole and to highlight future
      research directions.

PMID- 29201272
TI  - Resveratrol Ameliorates Mitochondrial Elongation via Drp1/Parkin/PINK1 Signaling
      in Senescent-Like Cardiomyocytes.
AB  - Resveratrol is widely known for its antiaging properties and exerts
      cardiovascular protective effects in different experimental models. The role of
      resveratrol in regulating mitochondrial functions and dynamics during the cardiac
      aging process remains poorly understood. In this study, the effects of
      resveratrol on mitochondrial morphology and mitochondrial depolarization and on
      expressions of Drp1, parkin, PINK1, and LC3 were investigated in H9c2 cells after
      D-galactose treatment that induced senescent-like cardiomyocytes. The results
      show that downregulation of Drp1 markedly increased mitochondrial elongation.
      Senescent-like cardiomyocytes were more resistant to CCCP-induced mitochondrial
      depolarization, which was accompanied by suppressed expression of parkin, PINK1,
      and LC3-II. Resveratrol treatment significantly increased Drp1 expression,
      ameliorated mitochondrial elongation, and increased the mitochondrial
      translocations of parkin and PINK1. In addition, resveratrol significantly
      enhanced LC3-II expression and decreased TOM20-labeled mitochondrial content.
      Resveratrol also suppressed the phosphorylation of parkin and PINK1, which may
      relate to its abilities to degrade the impaired mitochondria in senescent-like
      cardiomyocytes. These findings show that suppressing mitochondrial elongation in
      a Drp1-dependent manner is involved in the effect of resveratrol on attenuating
      the development of aging cardiomyocytes. Activation of parkin and PINK1 may be a
      potential mechanism of resveratrol for treating cardiovascular complications
      related to aging.

PMID- 29201273
TI  - Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular
      Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome.
AB  - Metabolic syndrome (MS) increases cardiovascular risk and is associated with
      cardiac dysfunction and arrhythmias, although the precise mechanisms are still
      under study. Chronic inflammation in MS has emerged as a possible cause of
      adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water
      and standard chow for 25-27 weeks were compared to a control group. The MS group
      showed increased weight, visceral fat, blood pressure, and serum triglycerides.
      The most important increases in serum cytokines included IL-1beta (7-fold), TNF
      alpha (84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased
      gene expression in heart tissue (35-fold). Heart function ex vivo in MS group
      showed a decreased mechanical performance response to isoproterenol challenge
      (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of
      ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum
      displayed impaired contractile function and Ca2+ handling during ISO treatment,
      showing slightly decreased cell shortening and Ca2+ transient amplitude (23%),
      slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+
      release events (7.5-fold). As spontaneous Ca2+ releases provide a substrate for
      ventricular arrhythmias, our study highlights the possible role of serum
      proinflammatory mediators in the development of arrhythmic events during MS.

PMID- 29201274
TI  - Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease.
AB  - Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is
      multifactorial and elusive. Mitochondrial dysfunction is a major feature of
      Alzheimer's pathology, which might be one of the early events that trigger
      downstream principal events. Here, we show that multiple genes that control
      mitochondrial homeostasis, including fission and fusion, are downregulated in
      Alzheimer's patients. Additionally, we demonstrate that some of these
      dysregulations, such as diminished DLP1 levels and its mitochondrial
      localization, as well as reduced STOML2 and MFN2 fusion protein levels, take
      place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of
      mitochondrial network disruption using CCCP indicates that the patients'
      fibroblasts exhibit slower dynamics and mitochondrial membrane potential
      recovery. These defects lead to strong accumulation of aged mitochondria in
      Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy
      involved genes in the patients demonstrates a downregulation indicating that the
      recycling mechanism of these aged mitochondria might be impaired. Our data
      reinforce the idea that mitochondrial dysfunction is one of the key early events
      of the disease intimately related with aging.

PMID- 29201275
TI  - Resveratrol and Montelukast Alleviate Paraquat-Induced Hepatic Injury in Mice:
      Modulation of Oxidative Stress, Inflammation, and Apoptosis.
AB  - Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is
      attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK)
      have anti-inflammatory and antioxidant properties. The protective effects of Res,
      MK, or their combination against PQ-induced acute liver injury have not been
      investigated before. Therefore, we explored the protective potential of Res
      and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly
      assigned to five groups: group I served as the normal control and group II
      received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ
      plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination,
      respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by
      normalization of serum total protein, ALT, and AST. Res and/or MK significantly
      reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res
      and/or MK significantly reduced PQ-induced inflammation reflected in TNF-alpha
      levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by
      differential expression of p53, Bax, and Bcl-2. Histopathologic examination
      supported the biochemical findings. Although Res and MK displayed antioxidative,
      anti-inflammatory, and antiapoptotic activities, their combination was not always
      synergistic.

PMID- 29201276
TI  - Antihypertensive Effects of Roselle-Olive Combination in L-NAME-Induced
      Hypertensive Rats.
AB  - This study aimed to evaluate the antihypertensive efficacy of a new combination
      therapy of Hibiscus sabdariffa and Olea europaea extracts (2 : 1; Roselle-Olive),
      using N(G)-nitro-L-arginine-methyl ester- (L-NAME-) induced hypertensive model.
      Rats received L-NAME (50 mg/kg/day, orally) for 4 weeks. Concurrent treatment
      with Roselle-Olive (500, 250, and 125 mg/kg/day for 4 weeks) resulted in a dose
      dependent decrease in both systolic and diastolic blood pressure, reversed the L
      NAME-induced suppression in serum nitric oxide (NO), and improved liver and
      kidney markers, lipid profile, and oxidative status. Furthermore, Roselle-Olive
      significantly lowered the elevated angiotensin-converting enzyme activity (ACE)
      and showed a marked genoprotective effect against oxidative DNA damage in
      hypertensive rats. Roselle-Olive ameliorated kidney and heart lesions and reduced
      aortic media thickness. Real-time PCR and immunohistochemistry showed an enhanced
      endothelial nitric oxide synthase (eNOS) gene and protein expression in both
      heart and kidney of Roselle-Olive-treated rats. To conclude, our data revealed
      that Roselle-Olive is an effective combination in which H. sabdariffa and O.
      europaea synergistically act to control hypertension. These effects are likely to
      be mediated by antioxidant and genoprotective actions, ACE inhibition, and eNOS
      upregulation by Roselle-Olive constituents. These findings provide evidences that
      Roselle-Olive combination affords efficient antihypertensive effect with a broad
      end-organ protective influence.

PMID- 29201277
TI  - Pre-operative Endocrine Therapy.
AB  - Purpose of Review: Pre-operative endocrine therapy can be used to down-stage
      large or locally advanced breast cancers in ER+ disease. In the last four
      decades, it has evolved from a treatment perceived as an alternative to surgery
      for those too unfit to undergo surgery or chemotherapy, to the present day where
      it is a valuable and valid option in the treatment of postmenopausal women with
      ER-rich (Allred score 7-8, or > 50% staining for ER) breast cancer. Recent
      Findings: Emerging data from the metastatic setting is translating into
      neoadjuvant trials, utilising dual endocrine targeting or combinations of
      endocrine agents and other targeted drugs, including those acting against
      components of the PI3K pathway and the cell cycle. The routine use of peri
      operative endocrine therapy in all ER+ tumours may help to yield important long
      term prognostic information, and guide adjuvant endocrine therapy. Summary: Pre
      operative endocrine therapy is an exciting and evolving area with emerging new
      approaches. In this review, established evidence and emerging data on its
      applications are discussed.

PMID- 29201278
TI  - Axillary Nodal Staging with Contrast-Enhanced Ultrasound.
AB  - Purpose of Review: Axillary staging in the context of breast cancer is a
      contentious topic due to the varied practices across UK, Europe, and America. The
      ACOSOG Z0011 trial has questioned the role of axillary ultrasound in women with
      breast cancer. Published data has shown that women with ultrasound-positive lymph
      nodes have a worse prognosis than those with ultrasound-negative lymph nodes.
      Axillary ultrasound is limited as the sentinel lymph node (SLN) cannot be
      identified using B-mode ultrasound; however, with the advent of contrast-enhanced
      ultrasound (CEUS), this has now changed. Recent Findings: The published
      literature has shown that the sentinel lymph node can be identified using CEUS.
      The rates are equivalent to blue dye alone but currently inferior to the dual
      technique of sentinel lymph node biopsy. There are several different contrast
      agents that can be used and the agents that remain in the sentinel lymph node for
      longer can identify areas of poor enhancement, allowing for targeted biopsy.
      Summary: CEUS has the potential to revolutionize the way we manage the axilla in
      the future and may even replace surgical staging.

PMID- 29201279
TI  - MAPPING AGE EFFECTS ALONG FIBER TRACTS IN YOUNG ADULTS.
AB  - Brain development is a protracted and dynamic process. Many studies have charted
      the trajectory of white matter development, but here we sought to map these
      effects in greater detail, based on a large set of fiber tracts automatically
      extracted from HARDI (high angular resolution diffusion imaging) at 4 tesla. We
      used autoMATE (automated multi-atlas tract extraction) to extract diffusivity
      measures along 18 of the brain's major fiber bundles in 667 young adults, aged 18
      30. We examined linear and non-linear age effects on diffusivity measures,
      pointwise along tracts. All diffusivity measures showed both linear and non
      linear age effects. Tracts with the most pronounced age effects were those that
      connected the temporal lobe to the rest of the brain. Nonlinear age effects were
      picked up strongly in the anterior corpus callosum and right temporo-parietal
      tracts.

PMID- 29201280
TI  - A NETWORK APPROACH TO EXAMINING INJURY SEVERITY IN PEDIATRIC TBI.
AB  - Traumatic brain injury (TBI) is the leading cause of death and disability in
      children, and can lead to long lasting functional impairment. Many factors
      influence outcome, but imaging studies examining effects of individual variables
      are limited by sample size. Roughly 20-40% of hospitalized TBI patients
      experience seizures, but not all of these patients go on to develop a recurrent
      seizure disorder. Here we examined differences in structural network connectivity
      in pediatric patients who had sustained a moderate-severe TBI (msTBI). We
      compared those who experienced early post-traumatic seizures to those who did
      not; we found network differences months after seizure activity stopped. We also
      examined correlations between network measures and a common measure of injury
      severity, the Glasgow Coma Scale (GCS). The global GCS score did not have a
      detectable relationship to brain integrity, but sub-scores of the GCS (eyes,
      motor, verbal) were more closely related to imaging measures.

PMID- 29201281
TI  - Graph theoretical approaches towards understanding differences in frontoparietal
      and default mode networks in Autism.
AB  - Autism Spectrum Disorder is a complex developmental disorder affecting 1 in 68
      children in the United States. While the prevalence may be on the rise, we
      currently lack a firm understanding of the etiology of the disease, and diagnosis
      is made purely on behavioral observation and informant report. As one method to
      improve our understanding of the disease, the current study took a systems-level
      approach by assessing the causal interactions among the frontoparietal and
      default mode networks using structural covariance of a large Autism dataset.
      Although preliminary, we report diffuse yet subtle changes throughout these
      networks when comparing age and sex matched controls to ASD patients.

PMID- 29201282
TI  - THE IMPACT OF MATCHING FUNCTIONAL ON ATROPHY MEASUREMENT FROM GEODESIC SHOOTING
      IN DIFFEOMORPHISMS.
AB  - Longitudinal registration has been used to map brain atrophy and tissue loss
      patterns over time, in both healthy and demented subjects. However, we have not
      seen a thorough application of the geodesic shooting in diffeomorphisms framework
      for this task. The registration model is complex and several choices must be made
      that may significantly impact the quality of results. One of these decisions is
      which image matching functional should drive the registration. We investigate
      four matching functionals for atrophy quantification using geodesic shooting in
      diffeomorphisms. We check if the choice of matching functional has an impact on
      the correlation of atrophy scores with clinical variables. We also check the
      impact of matching functional choice on estimates of the N80 sample size for
      hypothetical clinical trials that test for slowing of brain atrophy. We find that
      the mutual information function, which has primarily been used for linear and
      multi-modal registration, achieves comparable correlation with clinical variables
      to other matching functionals while yielding better sample size estimates.

PMID- 29201283
TI  - A COMPARISON OF NETWORK DEFINITIONS FOR DETECTING SEX DIFFERENCES IN BRAIN
      CONNECTIVITY USING SUPPORT VECTOR MACHINES.
AB  - Human brain connectomics is a rapidly evolving area of research, using various
      methods to define connections or interactions between pairs of regions. Here we
      evaluate how the choice of (1) regions of interest, (2) definitions of a
      connection, and (3) normalization of connection weights to total brain
      connectivity and region size, affect our calculation of the structural
      connectome. Sex differences in the structural connectome have been established
      previously. We study how choices in reconstruction of the connectome affect our
      ability to classify subjects by sex using a support vector machine (SVM)
      classifier. The use of cluster-based regions led to higher accuracy in sex
      classification, compared to atlas-based regions. Sex classification was more
      accurate when based on finer cortical partitions and when using dilations of
      regions of interest prior to computing brain networks.

PMID- 29201284
TI  - APPROXIMATING PRINCIPAL GENETIC COMPONENTS OF SUBCORTICAL SHAPE.
AB  - Optimal representations of the genetic structure underlying complex neuroimaging
      phenotypes lie at the heart of our quest to discover the genetic code of the
      brain. Here, we suggest a strategy for achieving such a representation by
      decomposing the genetic covariance matrix of complex phenotypes into maximally
      heritable and genetically independent components. We show that such a
      representation can be approximated well with eigenvectors of the genetic
      covariance based on a large family study. Using 520 twin pairs from the QTIM
      dataset, we estimate 500 principal genetic components of 54,000 vertex-wise shape
      features representing fourteen subcortical regions. We show that our features
      maintain their desired properties in practice. Further, the genetic components
      are found to be significantly associated with the CLU and PICALM genes in an
      unrelated Alzheimer's Disease (AD) dataset. The same genes are not significantly
      associated with other volume and shape measures in this dataset.

PMID- 29201285
TI  - Familial Trigeminal Neuralgia Treated with Stereotactic Radiosurgery: A Case
      Report and Literature Review.
AB  - Background: Trigeminal neuralgia (TN) is a chronic pain condition characterized
      by brief episodes of lancinating pain in one or more distributions of the
      trigeminal nerve. Episodes of pain secondary to TN are triggered by certain
      stimuli, such as chewing, shaving, or touching the face. Although a common cause
      of TN is compression of the trigeminal nerve root entry zone by an artery or
      vein, many cases of TN are idiopathic. However, there have been limited reports
      in the literature of familial TN. Case Presentation: A 31-year-old male presented
      with classic TN symptoms in the right V1/V2 distribution that recently progressed
      to the V3 distribution a case of familial TN. His father an brother both have TN.
      Carbamazepine, oxcarbazepine, and rhizotomy did not improve his symptoms. He was
      treated with stereotactic radiosurgery (SRS) with a dose of 85 Gy delivered to
      the proximal trigeminal root with improvement in his pain. We also review and
      summarize the over 160 cases of familial TN found in the literature. Conclusions:
      This is the first reported case of familial TN treated with SRS. Patients with
      familial TN are more likely to have bilateral disease, to present with earlier
      onset, and to become refractory to medical therapy and may require more
      aggressive approaches. We propose that SRS is a good treatment approach for these
      patients.

PMID- 29201286
TI  - Ideal Parent Figure method in the treatment of complex posttraumatic stress
      disorder related to childhood trauma: a pilot study.
AB  - Background: There is a consensus within the trauma field for the necessity of a
      three-phase treatment programme for complex posttraumatic stress disorder
      (CPTSD). This pilot study focuses on the stabilisation phase, the goal of which
      is the development of psychological resources and the reduction of disabling
      symptoms. Objective: To test the efficacy of the Ideal Parent Figure (IPF) method
      as a stabilization treatment for CPTSD patients with a history of childhood
      trauma. Method: The sample was comprised of 17 adults with a history of childhood
      trauma concomitant with CPTSD symptoms consulting at a clinic in France.
      Participants enrolled in a 5-week psychotherapy programme based on the IPF
      method, a semi-structured visualization programme designed to treat attachment
      disturbances. Measures of DESNOS symptoms, psychological symptoms, quality of
      life, and adult attachment were administered pre- and posttreatment as well as at
      8-month follow-up. Results: A significant decrease in symptom severity and
      attachment traumatization and a significant increase in quality of life were
      found, both with medium-to-large effect sizes. The 8-month follow-up assessment
      showed outcome stability. Conclusions: These results suggest that treating
      attachment disturbances directly with an approach akin to the Ideal Parent Figure
      method may lead to fast and stable improvement for individuals with CPTSD.

PMID- 29201287
TI  - Does size really matter? A multisite study assessing the latent structure of the
      proposed ICD-11 and DSM-5 diagnostic criteria for PTSD.
AB  - Background: Researchers and clinicians within the field of trauma have to choose
      between different diagnostic descriptions of posttraumatic stress disorder (PTSD)
      in the DSM-5 and the proposed ICD-11. Several studies support different competing
      models of the PTSD structure according to both diagnostic systems; however,
      findings show that the choice of diagnostic systems can affect the estimated
      prevalence rates. Objectives: The present study aimed to investigate the
      potential impact of using a large (i.e. the DSM-5) compared to a small (i.e. the
      ICD-11) diagnostic description of PTSD. In other words, does the size of PTSD
      really matter? Methods: The aim was investigated by examining differences in
      diagnostic rates between the two diagnostic systems and independently examining
      the model fit of the competing DSM-5 and ICD-11 models of PTSD across three
      trauma samples: university students (N = 4213), chronic pain patients (N = 573),
      and military personnel (N = 118). Results: Diagnostic rates of PTSD were
      significantly lower according to the proposed ICD-11 criteria in the university
      sample, but no significant differences were found for chronic pain patients and
      military personnel. The proposed ICD-11 three-factor model provided the best fit
      of the tested ICD-11 models across all samples, whereas the DSM-5 seven-factor
      Hybrid model provided the best fit in the university and pain samples, and the
      DSM-5 six-factor Anhedonia model provided the best fit in the military sample of
      the tested DSM-5 models. Conclusions: The advantages and disadvantages of using a
      broad or narrow set of symptoms for PTSD can be debated, however, this study
      demonstrated that choice of diagnostic system may influence the estimated PTSD
      rates both qualitatively and quantitatively. In the current described diagnostic
      criteria only the ICD-11 model can reflect the configuration of symptoms
      satisfactorily. Thus, size does matter when assessing PTSD.

PMID- 29201288
TI  - Cost-effectiveness analysis of ibrutinib in patients with Waldenstrom
      macroglobulinemia in Italy.
AB  - Background and Objective: Ibrutinib has recently been approved in Europe for
      Waldenstrom Macroglobulinemia (WM) in symptomatic patients who have received at
      least one prior therapy, or in first-line treatment for patients unsuitable for
      chemo-immunotherapy. The aim of the study is to estimate the incremental cost
      effectiveness ratio (ICER) of ibrutinib in relapse/refractory WM, compared with
      the Italian current therapeutic pathways (CTP). Methods: A Markov model was
      adapted for Italy considering the National Health System perspective. Input data
      from literature as well as global trials were used. The percentage use of
      therapies, and healthcare resources consumption were estimated according to
      expert panel advice. Drugs ex-factory prices and national tariffs were used for
      estimating costs. The model had a 15-year time horizon, with a 3.0% discount rate
      for both clinical and economic data. Deterministic and probabilistic sensitivity
      analyses were performed to test the results strength. Results: Ibrutinib resulted
      in increased Life Years Gained (LYGs) and increased costs compared to CTP, with
      an ICER of ?52,698/LYG. Sensitivity analyses confirmed the results of the
      BaseCase. Specifically, in the probabilistic analysis, at a willingness to pay
      threshold of ?60,000/LYG ibrutinib was cost-effective in 84% of simulations.
      Conclusions: Ibrutinib has demonstrated a positive cost-effectiveness profile in
      Italy.

PMID- 29201289
TI  - Evaluation of clinical variables according to follow-up times in COPD: results
      from ON-SINT cohort.
AB  - Background: COPD is a chronic disease traditionally associated with increased
      symptoms as lung function deteriorates. Follow-up times in previous cohort
      studies were limited to a few years. Interestingly, newer longer observational
      studies show a more comprehensive picture on disease progression over time.
      Therefore, the question on the relevancy of the follow-up time in cohort studies
      remains open. Methods: The ON-SINT study is an observational, retrospective,
      nationwide, real-life cohort study, in which patients diagnosed with COPD were
      recruited between December 2011 and April 2013 by primary care (PC) and secondary
      care (SC) physicians. Patients were evaluated at the inclusion visit and at the
      initial visit when the diagnosis of COPD was first established. Distribution of
      lung function decline over the years was studied comparing those cases with
      longer follow-up times, with the median of the distribution as the cutoff point.
      Results: The sample included 1214 patients of which 857 (70.6%) were recruited by
      PC and 357 (29.4%) by SC physicians. Median follow-up time was 6.26 years. Mean
      annual change in the complete cohort were -4.5 (222) ml year-1 for FVC and 5.5
      (134) ml year-1 for FEV1. We confirm the variable distribution of FEV1 decline
      and found that longer follow-up periods reduce this variability. Of note, FEV1
      decline was different between groups (shorter: 19.7 [180.4] vs longer: -9.7
      [46.9]; p = 0.018). Further, our data revealed differences in the clinical
      presentation according to follow-up times, with special emphasis on dyspnea (OR:
      1.035; 95%CI: 1.014-1.056), exacerbations (OR 1.172; 95%CI 1.045-1.315) and CAT
      scores (OR 1.047; 95%CI 1.019-1.075) being associated with longer follow-up
      times. Conclusions: This study describes the impact of follow-up periods on lung
      function variability, and reveals differences in clinical presentation according
      to follow-up times, with special emphasis on dyspnea, exacerbations and CAT
      scores.

PMID- 29201290
TI  - Ergospirometry with concurrent fibre optic laryngoscopy: a randomised crossover
      study.
AB  - Background: Patients suffering from exercise-induced laryngeal obstruction (EILO)
      are subjected to several exhausting tests. We aimed to assess the feasibility of
      using a single test to obtain diagnostic measurements for maximum oxygen uptake
      (VO2max) and exercise-induced laryngeal obstruction (EILO). Methods: Patients
      referred to the outpatient respiratory clinic at the University Hospital of
      Bispebjerg, Copenhagen with exercise-induced dyspnoea were evaluated for
      inclusion over 13 months. Eligible patients were aged 18-43 years, had a known
      EILO diagnosis (moderate or severe) and were inactive (self-reported activity)
      with less than 3 hours activity per week. In randomised order, all participants
      (n = 11) underwent three tests: a VO2max test with and without concurrent
      laryngoscopy. VO2max and EILO values from the two testing methods were compared.
      Findings: There was no difference in VO2max measured by ergospirometry with and
      without simultaneous continuous laryngoscopy during exercise (CLE) testing (mean
      difference -22 ml O2?min-1; 95% CI -125 to 81 ml O2?min-1; P = 0.647). EILO
      scores obtained during the CLE testing on the treadmill versus CLE testing on the
      ergometer bike revealed identical supraglottic scores in nine of the 11
      participants (82%) with substantial agreement between the two types of test (x =
      0.71). Glottic scores were identical in six of the 11 (55%), showing moderate
      agreement between test types (x = 0.38). Conclusions: Based on our findings in
      inactive individuals, ergospirometry with laryngoscopy is feasible and well
      tolerated, yielding measurements for maximal oxygen uptake comparable to those of
      standard bike ergospirometry. Likewise, measurements of supraglottic EILO are
      comparable to those of the standard treadmill CLE test.

PMID- 29201291
TI  - Long-term Results of Modified Salter Innominate Osteotomy for Legg-Calve-Perthes
      Disease.
AB  - Background: In a previous study, we reported clinical and radiographic results of
      our modified Salter innominate osteotomy technique in 16 hips affected by Legg
      Calve-Perthes disease (LCPD) with an average follow-up of 31.8 months. In this
      study, we present the long-term results of the osteotomy in LCPD patients
      followed until physeal closure. Methods: Thirty hips of 29 patients were followed
      until skeletal maturation after modified Salter innominate osteotomy. The mean
      follow-up duration was 12.9 years (range, 9.1 to 16.0 years). Eleven hips (36.7%)
      were classified as Catterall group III and 19 (63.3%) as Catterall group VI.
      Stable interposition of a bone block was achieved using one biodegradable screw
      in nine hips and without any fixation device in 21 hips by simply changing the
      direction of osteotomy. The Harris Hip Score (HHS), Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) score, and hip function were evaluated
      at the last follow-up. Radiological outcomes were evaluated using Wiberg's center
      edge angle, the Mose method, and Stulberg classification, and osteoarthritic
      changes were evaluated using the Tonnis classification. Results: Mean HHS and
      WOMAC score were 80.2 points and 54 points, respectively, preoperatively and
      these were improved to 96.2 points and 28 points, respectively, at the last
      follow-up. Clinical results, according to Robinson's criteria, were good in 18,
      fair in seven, and poor in five hips. Radiological results assessed using the
      Mose method were good in 18, fair in six, and poor in six hips, and according to
      the Stulberg classification, nine hips were class I, nine were class II, eight
      were class III, and four were class IV. The mean center-edge angle improved from
      19.7 degrees  preoperatively to 29.6 degrees  at the final follow-up. According
      the Tonnis classification, three hips were grade 2, five were grade 1, and 22
      were grade 0. Of the three grade 2 hips, two underwent Chiari osteotomy 12.1 and
      8.8 years postoperatively, and the other underwent total hip arthroplasty 12.9
      years postoperatively. Conclusions: The modified Salter innominate osteotomy
      produced relatively satisfactory long-term clinical and radiological results.

PMID- 29201292
TI  - Factors Associated with the Risk of Articular Surface Perforation during Anchor
      Placement for Arthroscopic Acetabular Labral Repair.
AB  - Background: The purpose of this study was to evaluate factors associated with the
      risk of articular surface perforation during anchor placement for arthroscopic
      acetabular labral repair using follow-up computed tomographic arthrography (CTA).
      Methods: Forty-six patients (29 males and 17 females) underwent arthroscopic
      labral repair using 142 suture anchors (55 large anchors and 87 small anchors).
      The patients were followed with CTA 1 year postoperatively. Anchor position was
      assessed by the insertion angle and the distance of the suture anchor tip from
      the articular cartilage. The incidence of malposition of suture anchors was
      assessed in follow-up CTA. The location and incidence of malposition were
      compared between two groups divided according to the diameter of suture anchor.
      Results: The mean insertion angle and distance were significantly different
      between the groups. Of the 142 anchors, 15 (11%) were placed in the cartilage
      bone transitional zone. Articular involvement was most common at the 3 o'clock
      position of the suture anchor (six out of 33 anchors, 18.2%). Both the insertion
      angle and distance showed small values in the articular involvement group.
      Conclusions: The radiographic analysis of the placement of suture anchors after
      arthroscopic labral refixation based on follow-up CTA demonstrates that articular
      involvement of anchors is related to the location on the acetabular rim (clock
      position) and anchor diameter.

PMID- 29201293
TI  - Calcar Femorale in Patients with Osteoarthritis of the Hip Secondary to
      Developmental Dysplasia.
AB  - Background: We investigated whether the calcar femorale, a cortical septum in the
      region of the lesser trochanter of the femur, correlates with results of femoral
      stem implantation in patients with osteoarthritis of the hip secondary to
      developmental dysplasia using computed tomography. Methods: This retrospective
      study included 277 hips (41 males and 236 females; age, 37 to 92 years) of
      patients who had presented to Okayama Medical Center with hip pain. Of these, a
      total of 219 hips (31 males and 188 females) had previously undergone total hip
      arthroplasty. According to the Crowe classification, 147 hips were classified as
      Crowe grade I, 72 hips as Crowe grade II-IV, and 58 hips as normal. Results: The
      calcar femorale was identified in 267 hips (96.4%). The calcar femorale was
      significantly shorter and more anteverted in Crowe grade II-IV hips than in Crowe
      grade I or normal hips. Significant differences in the shape of the calcar
      femorale were found according to the severity of hip deformity. Three stem
      designs were analyzed: single-wedge (59 hips), double-wedge metaphyseal filling
      (147 hips), and modular (13 hips). Single-wedge stems were inserted more parallel
      to the calcar femorale rather than femoral neck anteversion, while other types of
      stems scraped the calcar femorale. Conclusions: The angle of the calcar femorale
      differs according to the severity of hip deformity, and the calcar femorale might
      thus serve as a more useful reference for stem insertion than femoral neck
      anteversion in total hip arthroplasty using a single-wedge stem.

PMID- 29201294
TI  - Trend in the Age-Adjusted Incidence of Hip Fractures in South Korea: Systematic
      Review.
AB  - Background: The incidence of hip fractures has been reported to vary
      geographically, and its trend has also varied widely. However, the trend in the
      age-adjusted incidence of hip fractures has not been well studied in Korea. After
      we identified eligible studies presenting multiple age-adjusted incidences of hip
      fractures in the Korean population in PubMed, we evaluated changes in the
      absolute number of occurrence and calculated the annual percentage change (APC)
      of age-adjusted incidences of hip fractures. Methods: We have searched PubMed for
      the original and English-language literature on the incidence of hip fractures in
      the Korean population published since 2000. The studies presenting multiple age
      adjusted incidences of hip fractures were selected. We evaluated the change in
      the absolute number of hip fractures and calculated the APC of age-adjusted
      incidences of hip fractures for each study. Results: Three eligible articles were
      identified. The absolute number of hip fractures for both genders increased over
      time in all three studies although the operational definition of hip fracture
      differed from one another. The APC of the age-adjusted incidence of hip fractures
      was positive for women and negative for men. However, the change was not
      statistically significant in both genders during each study period (2001-2004,
      2005-2008, and 2006-2010, respectively). Conclusions: The age-adjusted incidence
      of hip fractures was stable among men and women, while the absolute number of hip
      fractures increased for both genders in Korea. Further studies with longer study
      periods on age-adjusted incidences are required to better determine the trend in
      the incidence of hip fractures in Korea.

PMID- 29201295
TI  - A Comparative Study of Clinical Outcomes and Second-Look Arthroscopic Findings
      between Remnant-Preserving Tibialis Tendon Allograft and Hamstring Tendon
      Autograft in Anterior Cruciate Ligament Reconstruction: Matched-Pair Design.
AB  - Background: This study aimed to compare stability, functional outcome, and second
      look arthroscopic findings after anterior cruciate ligament reconstruction
      between remnant-preserving tibialis tendon allograft and remnant-sacrificing
      hamstring tendon autograft. Methods: We matched two groups (remnant-preserving
      tibialis tendon allograft group and hamstring tendon autograft group) in terms of
      demographic characteristics, associated injury, and knee characteristics. Each
      group consisted of 25 patients. Results: Operation time was longer in the remnant
      preserving tibialis tendon allograft group, but there was no significant
      intergroup difference in stability, clinical outcome, and second-look
      arthroscopic findings. Conclusions: When an autograft is not feasible in anterior
      cruciate ligament reconstruction, the remnant-preserving technique can produce
      comparable results in terms of restoration of function, stability of the knee,
      and degree of synovium coverage at second-look arthroscopy compared to remnant
      sacrificing hamstring autograft.

PMID- 29201296
TI  - Predictors of Midterm Outcomes after Medial Unicompartmental Knee Arthroplasty in
      Asians.
AB  - Background: This study was designed to evaluate predictors of good outcomes
      following medial unicompartmental knee arthroplasty (UKA) in Asian patients.
      Methods: Registry data of patients who underwent primary unilateral medial UKA
      from 2006 to 2011 were collected. Outcomes studied were the Oxford Knee Score
      (OKS) and the Physical Component Score (PCS) of the Short Form 36 (SF-36)
      questionnaire. These outcome scores were collected prospectively, pre- and
      postoperatively up to 5 years. Good outcome was defined as an overall improvement
      in score greater than or equal to the minimal clinically important difference
      (MCID). The MCID for the OKS was 5 while the MCID for the PCS was 10. Regression
      analysis was used to identify predictors of good outcomes following medial UKA.
      Results: Primary medial UKA was performed in 1,075 patients. Higher (poorer)
      preoperative OKS (odds ratio [OR], 1.27; p < 0.001), lower (poorer) preoperative
      PCS (OR, 1.08; p < 0.001), lower (poorer) preoperative Knee Society Knee Score
      (KSKS; OR, 1.02; p < 0.001) and higher (better) preoperative SF-36 Mental
      Component Score (MCS; OR, 1.02; p < 0.001) were significant predictors of good
      outcomes. Conclusions: Patients with poorer OKS, PCS and KSKS and better SF-36
      MCS preoperatively tended to achieve good outcomes by the MCID criterion at 5
      years following the index surgery.

PMID- 29201297
TI  - A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of
      Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis.
AB  - Background: The aim of this study was to evaluate the safety and analgesic
      efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus
      celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis
      (OA). Methods: This study was a 6-week, phase III, randomized, double-blind, and
      parallel-group trial followed by an 18-week, single arm, open-label extension. Of
      the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed
      6 weeks of treatment and 220 completed the extension. Patients were randomized to
      receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n
      = 71) once daily for 6 weeks. During the extension, all participants received
      open-label polmacoxib 2 mg. The primary endpoint was the change in Western
      Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to
      week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain,
      stiffness, and physical function) and Physician's and Subject's Global
      Assessments at weeks 3 and 6. Other outcome measures included adverse events
      (AEs), laboratory tests, vital signs, electrocardiograms, and physical
      examinations. Results: After 6 weeks, the polmacoxib-placebo treatment difference
      was -2.5 (95% confidence interval [CI], -4.4 to -0.6; p = 0.011) and the
      polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; p = 0.425).
      According to Physician's Global Assessments, more subjects were "much improved"
      at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and
      general disorder AEs occurred with a greater frequency with polmacoxib or
      celecoxib than with placebo. Conclusions: Polmacoxib 2 mg was relatively well
      tolerated and demonstrated efficacy superior to placebo and noninferior to
      celecoxib after 6 weeks of treatment in patients with OA. The results obtained
      during the 18-week trial extension with polmacoxib 2 mg were consistent with
      those observed during the 6-week treatment period, indicating that polmacoxib can
      be considered safe for long-term use based on this relatively small scale of
      study in a Korean population. More importantly, the results of this study showed
      that polmacoxib has the potential to be used as a pain relief drug with reduced
      gastrointestinal side effects compared to traditional nonsteroidal anti
      inflammatory drugs for OA.

PMID- 29201298
TI  - Lateralization of Tibial Plateau Reference Point Improves Accuracy of Tibial
      Resection in Total Knee Arthroplasty in Patients with Proximal Tibia Vara.
AB  - Background: The tibial cut referenced to the center of the intercondylar eminence
      often leads to varus malalignment in the presence of preexisting proximal tibia
      vara. The purpose of this study was to investigate the effect of lateralization
      of the lateral tibial plateau reference point (based on the amount of proximal
      tibia vara) on the postoperative coronal plane alignment. Methods: In this
      prospective cohort study, 62 patients (95 knees) with osteoarthritis and proximal
      tibia vara underwent primary total knee arthroplasty using a lateral tibial
      plateau reference point for the extramedullary jig. The pre- and postoperative
      radiographs were obtained for measurement of mechanical axis deviation, degree of
      tibia vara, proximal lateral reference point of the tibial condyle, and coronal
      alignment of the femoral and tibial components. The distance between the tibial
      reference point and the center of the intercondylar eminence was measured
      intraoperatively. Results: The mean tibia vara was 7.1 degrees  (standard
      deviation [SD], 2.3 degrees ). The mean lateral displacement of the reference
      point was 7 mm (SD, 2.2 mm). Postoperative tibiofemoral angle was 6 degrees  to
      10 degrees  of valgus in 94% of cases. There was a strong correlation between the
      magnitude of tibia vara and the amount of lateralization of the tibial reference
      point (R2 = 0.79, p < 0.001). Conclusions: In total knee arthroplasty patients
      with proximal tibia vara, reasonable accuracy can be achieved with use of the
      extramedullary jig for tibial component alignment by lateralizing the proximal
      tibial reference point.

PMID- 29201299
TI  - The Relationship between Superior Disc-Endplate Complex Injury and Correction
      Loss in Young Adult Patients with Thoracolumbar Stable Burst Fracture.
AB  - Background: To determine the relationship between superior disc-endplate complex
      injury and correction loss after surgery in a group of young adult patients with
      a stable thoracolumbar burst fracture. Methods: The study group was comprised of
      young adult patients who had undergone short-segment posterior fixation and bone
      grafting under the diagnosis of a stable thoracolumbar burst fracture from March
      2008 to February 2014. Follow-up was available for more than 1 year. Before
      surgery, magnetic resonance imaging was performed to determine injury to the
      anterior longitudinal ligament, posterior longitudinal ligament, and superior and
      inferior intervertebral discs and endplates. Correction loss was evaluated by the
      Cobb angle, intervertebral disc height, upper intervertebral disc angle,
      vertebral wedge angle, and vertebral body height. Results: No significant
      relation was noted between correction loss and an injury to the anterior
      longitudinal ligament, posterior longitudinal ligament, inferior intervertebral
      disc/endplate, and fracture site, whereas an injury to the superior endplate
      alone and superior disc-endplate complex showed a significant association.
      Specifically, a superior intervertebral disc-endplate complex injury showed
      statistically significant relation to postoperative changes in Cobb angle (p =
      0.026) and vertebral wedge angle (p = 0.047). Conclusions: A superior
      intervertebral disc-endplate complex injury may have an influence on the
      prognosis after short-segment fixation in young adult patients with a stable
      thoracolumbar burst fracture.

PMID- 29201300
TI  - The Validation of Ultrasound-Guided Target Segment Identification in Thoracic
      Spine as Confirmed by Fluoroscopy.
AB  - Background: The role of ultrasound in the thoracic spine has been
      underappreciated, partly because of the relative efficacy of the landmark-guided
      technique and the limitation of imaging through the narrow acoustic windows
      produced by the bony framework of thoracic spine. The aim of this study was to
      make a comparison between the 12th rib and the spinous process of C7 as a
      landmark for effective ultrasound-guided target segment identification in the
      thoracic spine. Methods: Ultrasonography of 44 thoracic spines was performed and
      the same procedure was carried out 1 week later again. The target segments (T3-4,
      T7-8, and T10-11) were identified using the 12th rib (group 1) or the spinous
      process of C7 (group 2) as a starting landmark. Ultrasound scanning was done
      proximally (group 1) or distally (group 2) toward the target transverse process
      and further medially and slightly superior to the target thoracic facet. Then, a
      metal marker was placed on the T3-4, T7-8, and T10-11 and the location of each
      marker was confirmed by fluoroscopy. Results: In the total 132 segments,
      sonographic identification was confirmed to be successful with fluoroscopy in
      84.1% in group 1 and 56.8% in group 2. Group 1 had a greater success rate in
      ultrasound-guided target segment identification than group 2 (p = 0.001),
      especially in T10-11 (group 1, 93.2%; group 2, 43.2%; p = 0.001) and T7-8 (group
      1, 86.4%; group 2, 56.8%; p = 0.002). The intrarater reliability of ultrasound
      guided target segment identification was good (group 1, r = 0.76; group 2, r =
      0.82), showing no difference between right and left sides. Ultrasound-guided
      target segment identification was more effective in the non-obese subjects (p =
      0.001), especially in group 1. Conclusions: Ultrasound-guided detection using the
      12th rib as a starting landmark for scanning could be a promising technique for
      successful target segment identification in the thoracic spine.

PMID- 29201301
TI  - Effects of Different Angles of the Traction Table on Lumbar Spine Ligaments: A
      Finite Element Study.
AB  - Background: The traction bed is a noninvasive device for treating lower back pain
      caused by herniated intervertebral discs. In this study, we investigated the
      impact of the traction bed on the lower back as a means of increasing the disc
      height and creating a gap between facet joints. Methods: Computed tomography (CT)
      images were obtained from a female volunteer and a three-dimensional (3D) model
      was created using software package MIMICs 17.0. Afterwards, the 3D model was
      analyzed in an analytical software (Abaqus 6.14). The study was conducted under
      the following traction loads: 25%, 45%, 55%, and 85% of the whole body weight in
      different angles. Results: Results indicated that the loading angle in the L3-4
      area had 36.8%, 57.4%, 55.32%, 49.8%, and 52.15% effect on the anterior
      longitudinal ligament, posterior longitudinal ligament, intertransverse ligament,
      interspinous ligament, and supraspinous ligament, respectively. The respective
      values for the L4-5 area were 32.3%, 10.6%, 53.4%, 56.58%, and 57.35%. Also, the
      body weight had 63.2%, 42.6%, 44.68%, 50.2%, and 47.85% effect on the anterior
      longitudinal ligament, posterior longitudinal ligament, intertransverse ligament,
      interspinous ligament, and supraspinous ligament, respectively. The respective
      values for the L4-5 area were 67.7%, 89.4%, 46.6%, 43.42% and 42.65%. The
      authenticity of results was checked by comparing with the experimental data.
      Conclusions: The results show that traction beds are highly effective for disc
      movement and lower back pain relief. Also, an optimal angle for traction can be
      obtained in a 3D model analysis using CT or magnetic resonance imaging images.
      The optimal angle would be different for different patients and thus should be
      determined based on the decreased height of the intervertebral disc, weight and
      height of patients.

PMID- 29201302
TI  - Antibiotic Spacers in Shoulder Arthroplasty: Comparison of Stemmed and Stemless
      Implants.
AB  - Background: Antibiotic spacers in shoulder periprosthetic joint infection deliver
      antibiotics locally and provide temporary stability. The purpose of this study
      was to evaluate differences between stemmed and stemless spacers. Methods: All
      spacers placed from 2011 to 2013 were identified. Stemless spacers were made by
      creating a spherical ball of cement placed in the joint space. Stemmed spacers
      had some portion in the humeral canal. Operative time, complications,
      reimplantation, reinfection, and range of motion were analyzed. Results: There
      were 37 spacers placed: 22 were stemless and 15 were stemmed. The stemless spacer
      population was older (70.9 +/- 7.8 years vs. 62.8 +/- 8.4 years, p = 0.006). The
      groups had a similar percentage of each gender (stemless group, 45% male vs.
      stemmed group, 40% male; p = 0.742), body mass index (stemless group, 29.1 +/-
      6.4 kg/m2 vs. stemmed group, 31.5 +/- 8.3 kg/m2; p = 0.354) and Charlson
      Comorbidity Index (stemless group, 4.2 +/- 1.2 vs. stemmed group, 4.2 +/- 1.7; p
      = 0.958). Operative time was similar (stemless group, 127.5 +/- 37.1 minutes vs.
      stemmed group, 130.5 +/- 39.4 minutes). Two stemless group patients had self
      resolving radial nerve palsies. Within the stemless group, 15 of 22 (68.2%)
      underwent reimplantation with 14 of 15 having forward elevation of 109 degrees 
      +/- 23 degrees . Within the stemmed group, 12 of 15 (80.0%, p = 0.427) underwent
      reimplantation with 8 of 12 having forward elevation of 94 degrees  +/- 43
      degrees  (range, 30 degrees  to 150 degrees ; p = 0.300). Two stemmed group
      patients had axillary nerve palsies, one of which self-resolved but the other did
      not. One patient sustained dislocation of reverse shoulder arthroplasty after
      reimplantation. One stemless group patient required an open reduction and
      glenosphere exchange of dislocated reverse shoulder arthroplasty at 6 weeks after
      reimplantation. Conclusions: Stemmed and stemless spacers had similar clinical
      outcomes. When analyzing all antibiotic spacers, over 70% were converted to
      revision arthroplasties. The results of this study do not suggest superiority of
      either stemmed or stemless antibiotic spacers.

PMID- 29201303
TI  - Bridging Graft in Irreparable Massive Rotator Cuff Tears: Autogenic Biceps Graft
      versus Allogenic Dermal Patch Graft.
AB  - Background: Few comparative studies have reported on the use of biologic grafts
      for irreparable massive rotator cuff tears. The purpose of this study was to
      assess the results of arthroscopic bridging graft in irreparable massive rotator
      cuff tears using an autogenic long head of biceps tendon (LHBT) or an allogenic
      dermal patch (ADP). Methods: We retrospectively reviewed 24 patients treated
      using the LHBT (group I) and eight patients with complete rupture of the LHBT
      treated using an ADP (group II) since 2011. Preoperative Goutallier's fatty
      degeneration, range of motion (ROM), visual analogue scale (VAS) for pain,
      American Shoulder and Elbow Surgeons (ASES) score, and Quick Disabilities of the
      Arm, Shoulder, and Hand (DASH) score were assessed and healing failure was
      evaluated at 1 year after surgery by ultrasonography or magnetic resonance
      imaging. Results: The mean fatty degeneration in groups I and II was 3.9 and 3.6
      for the supraspinatus (p = 0.288), 2.7 and 2.9 for the infraspinatus (p = 0.685),
      0.9 and 1.3 for the subscapularis (p = 0.314), and 1.3 and 3.0 for the teres
      minor (p = 0.005), respectively. Subscapularis tears were found in 8 patients
      (33.3%) in group I and in 7 patients (87.5%) in group II (p = 0.023). Mean ROMs
      and functional scores improved significantly in group I (forward flexion: 121.7
      degrees  to 153.3 degrees , p = 0.010; external rotation: 32.7 degrees  to 52.7
      degrees , p = 0.001; external rotation at 90 degrees : 63.3 degrees  to 74.5
      degrees , p = 0.031; internal rotation: T10.5 to T9.3, p = 0.045; VAS: 7.0 to
      1.1, p < 0.001; ASES score: 45.4 to 81.6, p = 0.028; and Quick DASH score: 50.0
      to 14.2, p = 0.017), whereas only VAS showed significant improvement in group II
      (from 5.9 to 2.0, p = 0.025) and ROMs and other functional scores increased
      without statistical significance in the group. Healing failure was found in 13
      patients (54.2%) in group I and in 6 patients (75.0%) in group II (p = 0.404).
      Conclusions: The surgeon should prudently choose surgical options for irreparable
      massive rotator cuff tears, especially in patients with severe fatty degeneration
      in the teres minor or combined biceps and subscapularis tears.

PMID- 29201304
TI  - Minimally Invasive Plate Osteosynthesis Using a Screw Compression Method for
      Treatment of Humeral Shaft Fractures.
AB  - Background: This study aims to compare the surgical outcomes of open reduction
      and internal fixation (ORIF) and minimally invasive plate osteosynthesis (MIPO)
      using a screw compression method in simple humeral shaft fractures. Methods: This
      retrospective study was performed with 50 patients who had surgical interventions
      for the treatment of simple humeral shaft fractures and had follow-ups of at
      least 12 months in Ulsan University Hospital between August 2008 and June 2015.
      Group 1 included 23 patients treated with ORIF and group 2 included 27 patients
      treated with the MIPO technique using a locking screw plate. The time to
      clinical/radiographic union, the joint range of motion (ROM), and function were
      evaluated. Results: The average time to clinical/radiographic bone union was
      shorter in group 2 (12.0 +/- 3.7 weeks/14.8 +/- 2.0 weeks in group 1 and 9.4 +/-
      1.3 weeks/12.0 +/- 3.3 weeks in group 2; p = 0.022/p = 0.034). Shoulder and elbow
      joint function evaluated by joint ROM and visual analogue scale (VAS), Korean
      Shoulder Elbow Society (KSS), American Shoulder and Elbow Surgeons (ASES), and
      the University of California at Los Angeles (UCLA) scores was excellent in both
      groups. On the average shoulder ROM at 12 months after the operation, group 1 had
      forward elevation of 160 degrees , external rotation of 30 degrees  in adduction
      and lumbar vertebra 10 level in internal rotation and group 2 had forward
      elevation of 170 degrees , external rotation of 35 degrees  in adduction and
      lumbar vertebra 9 level in internal rotation. The mean VAS, KSS, ASES, and UCLA
      scores were 2.8, 87.0 +/- 0.9, 89.4 +/- 0.9, and 31.0 +/- 1.4, respectively, in
      group 1 and 1.7, 89.1 +/- 2.7, 91.0 +/- 1.6, and 32.4 +/- 3.2, respectively, in
      group 2. There were statistically significant intergroup differences in VAS score
      (p = 0.011). There were significantly less postoperative infections in group 2
      (three cases, 10.7% in group 1 and 0 case in group 2; p = 0.041) although all of
      them were superficial infections and well-treated by an average 4-week course of
      antibiotics (range, 2 to 6 weeks). Conclusions: MIPO using a screw compression
      method in simple humeral shaft fractures demonstrated superior efficacy to ORIF
      in terms of the time to clinical/radiographic union, pain score, and
      postoperative infection rate.

PMID- 29201305
TI  - Biomechanical Comparison Study of Three Fixation Methods for Proximal Chevron
      Osteotomy of the First Metatarsal in Hallux Valgus.
AB  - Background: Fixation of proximal chevron metatarsal osteotomy has been
      accomplished using K-wires traditionally and with a locking plate recently.
      However, both methods have many disadvantages. Hence, we developed an
      intramedullary fixation technique using headless cannulated screws and conducted
      a biomechanical study to evaluate the superiority of the technique to K-wire and
      locking plate fixations. Methods: Proximal chevron metatarsal osteotomy was
      performed on 30 synthetic metatarsal models using three fixation techniques.
      Specimens in group I were fixated with K-wires (1.6 mm * 2) and in group II with
      headless cannulated screws (3.0 mm * 2) distally through the intramedullary
      canal. Specimens in group III were fixated with a locking X-shaped plate (1.3-mm
      thick) and screws (2.5 mm * 4). Eight metatarsal specimens were selected from
      each group for walking fatigue test. Bending stiffness and dorsal angulation were
      measured by 1,000 repetitions of a cantilever bending protocol in a plantar to
      dorsal direction. The remaining two samples from each group were subjected to 5
      mm per minute axial loading to assess the maximal loading tolerance. Results: All
      samples in group I failed walking fatigue test while group II and group III
      tolerated the walking fatigue test. Group II showed greater resistance to bending
      force and smaller dorsal angulation than group III (p = 0.001). On the axial
      loading test, group I and group II demonstrated superior maximum tolerance to
      group III (54.8 N vs. 47.2 N vs. 28.3 N). Conclusions: Authors have demonstrated
      proximal chevron metatarsal osteotomy with intramedullary screw fixation provides
      superior biomechanical stability to locking plate and K-wire fixations. The new
      technique using intramedullary screw fixation can offer robust fixation and may
      lead to better outcomes in surgical treatment of hallux valgus.

PMID- 29201306
TI  - Analysis of Radiographic Parameters of the Forearm in Traumatic Radial Head
      Dislocation.
AB  - Background: Various deformities can occur in the forearm bones when the
      traumatically dislocated radial head is untreated for a long period. Without
      correction of all deformities, reduction of the dislocated radial head is
      difficult to maintain, and forearm and elbow motion will deteriorate after
      reduction. We evaluated radiographic parameters of forearms with traumatically
      dislocated radial heads (and of the normal sides) to understand the resulting
      deformities and the effectiveness of surgical treatment. Methods: We analyzed pre
      and postoperative anteroposterior and lateral radiographs of 22 forearms (22
      patients) with traumatic radial head dislocation. We divided the forearm into
      three equal parts and measured various morphological parameters. All patients
      underwent surgical treatment and evaluation of radial head reduction and range of
      motion pre- and postoperatively. Results: Before treatment, the middle of the
      ulna was significantly different from the unaffected side in both anteroposterior
      and lateral views. After surgery, the proximal ulna was significantly different
      from the unaffected side and the abnormal proximal radial neck angle persisted.
      The radial head was successfully reduced in 20 of 22 cases. Overall, the mean
      range of motion decreased after surgery, except for increased flexion-extension.
      Conclusions: Complicated deformities developing during long-term remodeling after
      injury indicate that stable reduction is difficult to achieve with conventional
      one-bone osteotomy. Even after successful reduction, secondary deformity in the
      proximal ulna and/or remaining deformity in the proximal radius can hinder
      forearm rotation.

PMID- 29201307
TI  - Ischiofemoral Impingement Syndrome: Outcomes of Endoscopic Resection of the
      Lesser Trochanter.
AB  - Ischiofemoral impingement syndrome is a rare clinical entity characterized by
      chronic groin, buttock or hip pain associated with radiographic evidence of
      narrowing of the space between the lesser femoral trochanter and the ischial
      tuberosity. Introduction of magnetic resonance imaging to the clinical practice
      as well as the establishment of the radiological definition of the abnormal
      ischiofemoral distance has led to an increasing interest in this condition.
      Ischiofemoral impingement syndrome is a poorly understood disorder of chronic
      pain, especially regarding its treatment. The authors present two cases of
      primary ischiofemoral impingement syndrome successfully treated with a minimally
      invasive surgical technique. With this endoscopic technique, it was possible to
      resect the lesser trochanter and restore the ischiofemoral space. Immediate
      clinical and functional improvement was reported by both patients.

PMID- 29201308
TI  - A Rare Case of Intra-Articular Displacement of EndoButton Following Anterior
      Cruciate Ligament Reconstruction.
AB  - The EndoButton is a commonly used device for femoral fixation of anterior
      cruciate ligament grafts. Complications from its usage remain rare. Incorrect
      femoral tunnel placement may increase the risk of intra-articular displacement of
      the EndoButton. We present a case of anterior femoral tunnel placement resulting
      in intra-articular displacement of the EndoButton after failure. A 24-year-old
      man presented to us after failure of anterior cruciate ligament reconstruction
      performed 3 years prior. Radiographs revealed an intra-articular displacement of
      the EndoButton. Intraoperatively, it was noted that the femoral tunnel exit was
      within the suprapatellar pouch, with the displaced EndoButton lodged between the
      posterior aspect of the lateral tibial plateau and the capsule. Intra-articular
      displacement of the EndoButton is a rare complication and has only been reported
      twice in the literature. Anterior placement of the femoral tunnel may predispose
      patients to this complication and it is recommended to check the EndoButton
      position intraoperatively to avoid such a complication, especially for the
      unexperienced surgeon.

PMID- 29201309
TI  - Little Leaguer's Shoulder Can Cause Severe Three-Dimensional Humeral Deformity.
AB  - We analyzed three-dimensional (3D) humeral deformity (valgus-varus, flexion
      extension, and rotational deformation) after little leaguer's shoulder using 3D
      computed tomography in a 15-year-old male baseball player. Humeral retroversion
      was increased by 27.1 degrees  on the dominant side compared with the nondominant
      side. Compared with the nondominant shaft, the dominant humeral shaft was
      deformed in the varus direction (9.4 degrees ), resulting in a decreased neck
      shaft angle (dominant side, 127.5 degrees ; nondominant side, 135.1 degrees ),
      and it was also deformed in the extension direction (21.0 degrees ). This case
      demonstrates that little leaguer's shoulder can cause markedly greater humeral
      retroversion than has been reported previously and can result in varus and
      extension deformation of the humerus. These findings suggest that humeral
      deformity in overhead throwing athletes may not always solely reflect adaptation
      to throwing.

PMID- 29201310
TI  - A Neglected Markedly Displaced Medial Epicondyle Fracture with Simultaneous Ulnar
      Nerve Palsy in an Adolescent.
AB  - Humeral medial epicondyle fractures constitute around 15% of pediatric elbow
      fractures. Up to 60% occur in association with elbow dislocations. Knowledge of
      potential imaging pitfalls when examining acute elbow fractures in children
      contributes significantly to accurate diagnosis. Nevertheless, management of
      missed pediatric medial epicondyle fractures has rarely been reported. We present
      an 11-year-old boy with a neglected and severely displaced medial epicondyle
      fracture with concurrent ulnar nerve palsy. We performed neural decompression,
      fragment excision, and muscular and capsuloligamentous reconstruction of the
      medial elbow. This study demonstrates that the surgical outcome of a late
      presenting fracture can be satisfactory in terms of function and neural recovery.
      It also underscores the importance of careful interpretation of elbow imaging
      including normal anatomic variants.

PMID- 29201311
TI  - Synovial Sarcoma Complicating Total Knee Arthroplasty.
AB  - Synovial sarcoma is a relatively common periarticular soft tissue malignancy,
      occurring mostly in the extremities of younger patients. Occasionally, diversity
      in its clinical features may lead to misdiagnosis and inappropriate management.
      The authors report herein a unique case of a patient who underwent a primary
      total knee arthroplasty to treat osteoarthritis. During the operation, a mass was
      discovered but was attributed to synovitis. Biopsy revealed a rare intra
      articular synovial sarcoma. The patient underwent reoperation with wide excision
      and endoprosthesis placement and is disease-free at the 8-year follow-up.

PMID- 29201312
TI  - Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside.
AB  - Immunotherapy has been used for years in many types of cancer therapy. Recently,
      cancer immunotherapy has focused on mechanisms which can enhance the development
      of cell-mediated immunity. Anticancer medications are administered to inhibit
      immunosuppressive factors such as nagalase enzyme, which is produced by
      neoplastic cells and destroys macrophage activating factor (Gc-MAF). Anti
      neoplastics medications can also enhance immune-cell activity against tumors.
      Such medications show great potential in cancer immunotherapy using natural human
      mechanisms against neoplasms.

PMID- 29201313
TI  - Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A
      systematic review and meta-analysis.
AB  - Background: Hearing disorders are reported in thalassemia patients treated with
      deferoxamine. This study aimed to assess hearing loss in Iranian thalassemia
      major patients treated with deferoxamine. Methods: This review article was
      designed based on PRISMA guidelines. To review the literature, two researchers
      studied national and international databases including Iranmedex, Magiran,
      Medlib, SID, Scopus, PubMed, Science Direct, Web of Science and Google Scholar
      without time limit until May 2017. Cochran's Q test and I2 index were used to
      assess the heterogeneity of the studies. The data were analyzed using
      Comprehensive Meta-Analysis software version 2 and p<0.05 was considered
      significant. Results: A total of 17 articles involving 1,835 Iranian thalassemia
      major patients treated with deferoxamine were included in the meta-analysis. The
      overall prevalence of hearing loss was estimated 27.3% (95% confidence intervals
      (CI): 19-37.6). The prevalence of sensorineural, conductive and mixed hearing
      loss was estimated 10.6% (95% CI: 5.7-18.8), 14.6% (95% CI: 10.5-20.6) and 9.1%
      (95% CI: 5.6-14.6), respectively. No significant differences were noted regarding
      the relationship hearing loss and mean serum ferritin (P=0.29) and average daily
      deferoxamine (P=0.30). Meta-regression model showed an increased significance in
      the prevalence of hearing loss based on the year of studies (p<0.0001).
      Conclusions: There is a high prevalence of hearing loss in Iranian thalassemia
      major patients treated with deferoxamine. Therefore, periodic hearing assessments
      and regular check-ups after the initiation of chelation therapy are necessary.

PMID- 29201314
TI  - Serum albumin level as an indicator of response to Hepatitis B vaccination in
      dialysis patients: A systematic review and meta-analysis.
AB  - Background: Hepatitis B (HB) vaccination is a recommended procedure in all
      dialysis patients, but its efficacy has not been perfect. In the current study,
      we aimed to conduct a comprehensive review of the literature to find and pool
      data of the randomized trials evaluating the impact of serum albumin levels on
      the immunogenicity of HB vaccination in dialysis patients. Methods: Literature
      searches were conducted by the Medline and Google Scholar. The key words used
      included 'Hepatitis B', 'Vaccine', 'Dialysis', 'Hemodialysis', and 'Albumin'.
      Data of serum albumin levels regarding seroresponse to HB vaccine in clinical
      trials have been achieved and analyzed. Finally, data from 17 clinical trials
      have been pooled and analyzed. Results: One thousand six hundred eighty-two
      dialysis patients (1212 seroconverted) were included in the meta-analysis.
      Analysis of response to HB vaccination in our dialysis population showed a
      significant relationship to their serum albumin levels (p<0.001, z= 5.23).
      Regarding the dialysis mode, serum albumin level was only a significant
      interfering factor in hemodialysis patients versus continuous ambulatory
      peritoneal dialysis (CAPD) (HD group: p<0.001, I2=88.5%, chi2=95.28 (d.f. = 11);
      CAPD (+/-HD) group: chi2= 2.21; P=0.697, I2= 0%, d.f.= 4). Conclusion: The data
      showed a significant effect for the levels of serum albumin on the immunogenicity
      of HB vaccine in dialysis patients. Moreover, stratification of data upon
      dialysis mode showed that this association is only available for hemodialysis
      patients, and not those on peritoneal dialysis.

PMID- 29201315
TI  - A stochastic mathematical model of avascular tumor growth patterns and its
      treatment by means of noises.
AB  - Due to the rate increase in cancer incidence, many researchers in different
      fields have been conducting studies on cancer-related phenomena. Most studies are
      conducted to focus on cellular and molecular aspects of cancerous diseases and
      treatment strategies. Physicists have been using mathematical modeling and
      simulation to explain the growth pattern of tumors. Although most published
      studies in this area still have not gained the needed maturity for "treating
      cancer", research has helped with the statistical laws of growth, predation and
      proliferation of cancer cells. In this review, a brief explanation of
      mathematical models for tumor growth is presented, followed by a discussion on
      treatment simulations, introducing white noise as one of the clinical remedies in
      the original model.

PMID- 29201316
TI  - Three cycles of AC chemotherapy regimen increased oxidative stress in breast
      cancer patients: A clinical hint.
AB  - Background: Recent studies have suggested the importance of oxidant/antioxidant
      status in initiation and progression of breast cancer. The aim of this study was
      to evaluate oxidative stress markers in breast cancer patients before and after 3
      cycles of chemotherapy with adriamycin and cytoxan (AC). Also, in this study the
      effect of age and the stage of disease on oxidative stress markers were compared
      and evaluated. Methods: This study included 60 women with newly diagnosed stage
      II-III breast cancer who underwent chemotherapy with AC as the therapy-first
      strategy after surgery. Serum samples were obtained before treatment and after
      the third chemotherapy. Then, serum total antioxidant status (TAS) and
      malondialdehyde (MDA) as lipid peroxidation marker were analyzed. Moreover, the
      effects of the subject's age and clinical disease stage were investigated.
      Results: A concurrent significant increase in MDA (p<0.001) and a significant
      decrease in TAS (p<0.001) were also observed after 3 cycles of AC chemotherapy.
      In addition, some changes were found in the status of oxidative stress markers
      which were associated with age and clinical disease stage. Conclusion: Our data
      indicated that chemotherapy with AC increase the oxidative stress in breast
      cancer patients. The present study indicated that higher stages of the breast
      cancer are associated with significant increases of oxidative stress markers.

PMID- 29201317
TI  - Nailfold capillaroscopy in 430 patients with rheumatoid arthritis.
AB  - Background: Microvascular changes are one of the first obvious steps in numerous
      inflammatory diseases such as rheumatoid arthritis (RA). Nailfold video
      capillaroscopy (NFC) is an easy, reliable and safe method for evaluating
      peripheral microangiopathy. The objective of this study was to examine nailfold
      microcirculation in RA patients, assess morphological and structural changes
      quantitatively and qualitatively, and recognize useful changes. Methods: A total
      of 430 patients diagnosed with RA were examined in a period of 4 years. NFC was
      performed on all fingers of both hands in each patient. Different parameters
      indicating microvascular changes were detected and analyzed; such as
      microvascular architecture, capillary distribution disturbances, capillary
      morphology, capillary density, efferent/afferent limb ratio, subpapillary venular
      plexus and morphological abnormalities. The obtained results were categorized
      into normal pattern, nonspecific morphological abnormality and scleroderma
      pattern. Results: The mean age of participants was 51.03+/-14.54 (19-87 years)
      that consisted of 359 females and 71 males. Based on the findings, angiogenesis
      (74.7%) was the most pathological condition observed after tortuosity (99.5%).
      7.2% and 20.9% of patients were categorized into normal and scleroderma pattern
      group, respectively. Among morphological abnormalities, angiogenesis, isolated
      enlarged loop, irregular enlarged loop and architectural derangement were
      significantly more frequent in scleroderma than normal pattern (p<0.001).
      Conclusion: NFC may play an important role in monitoring RA disease and patients'
      follow-up. Therefore, in our opinion it could be considered in the course and
      follow-up of rheumatoid arthritis.

PMID- 29201318
TI  - Antibiotic resistance status and its costs in hematological patients: A two-year
      analysis.
AB  - Background: Most frequently, empirical antibiotic therapy is immediately
      administered for patients with febrile neutropenia (FN). In this study, its aim
      was to assess the antibiotic resistance status and the cost of antibacterial
      agents in FN patients associated with hematological malignancies. Methods: The
      cost of antibacterial agents used in FN episodes in patients with hematologic
      neoplasms followed-up at the Department of Hematology from November 2010 to
      November 2012 were analyzed retrospectively. Results: In the study period, 15 of
      141 patients who were admitted to the hematology ward and ineligible for the
      study criteria were excluded. In total, 282 febrile episodes of 126 consecutive
      patients with neutropenia were retrospectively investigated. Imipenem was found
      to be the most commonly used among the antibacterial drugs as 1.16 patient daily
      dose (PDD)/100 patient-days, 117.16 is the mean defined daily dose (DDD) per
      month and US $73264.66 total cost per year, followed by meropenem, cefoperazone
      sulbactam, and linezolid. Conclusion: Choosing noncarbapenem-based antibacterial
      therapy for empirical treatment of FN until the growth of microorganisms and
      switching to carbapenem therapy subsequent to new radiological, or
      microbiological, or/ and clinical findings, the appropriate vancomycin use may
      decrease the cost of antibacterial agents in the treatment of FN episodes in
      patients with hematologic malignancies contributing to antimicrobial stewardship.

PMID- 29201319
TI  - Potential drug-drug interactions among hospitalized patients in a developing
      country.
AB  - Background: Drug-drug interactions (DDIs) may often lead to preventable adverse
      drug events and health damage. Particularly in hospitals, this might be an
      important factor as multiple drug therapies are common. The objective of this
      study was to identify the frequency and levels of potential DDIs in internal
      medicine wards in an Iranian university hospital. Methods: A cross-sectional
      study was conducted by reviewing charts of 448 hospitalized patients in internal
      medicine wards of a teaching hospital, from November 2014 to May 2015. "Lexicomp
      drug interaction software" and Micromedex Drug-Reax system were used for
      screening the potential DDIs. The identified DDIs were categorized by level of
      severity. Logistic regression was applied to determine the odds ratio for
      specific risk factors of potential DDIs e.g., age, gender, hospital stay and
      number of medications. Results: The mean age of patients was 61 years, the length
      of hospital stay for patients was 9 days and the number of drugs per patient was
      9. Potential interactions were detected in 386 patients. The most common types of
      interactions were type C (78.6%), moderate (60.9%) and delayed onset (56.5%).
      There was a significant association of the occurrence of potential DDIs with
      seven or more numbers of prescribed medications (OR: 0.048, 95% CI:0.02-0.12,
      p<0.0001). Conclusion: The present study has recorded a high prevalence of
      potential DDIs in internal medicine wards. Patients with polypharmacy were at
      high risk for DDIs. Education, computerized prescribing systems, drug
      information, and pharmaceutical care are important measures that were recommended
      to minimize harm associated with DDIs.

PMID- 29201320
TI  - Does the low-density lipoprotein cholesterol play a key role in predicting
      metabolic syndrome in the Iranian adult population?
AB  - Background: The low density lipoprotein cholestrol (LDL-C) has an important role
      in the pathogenesis of cardiovascular disease but its association and predictive
      accuracy with metabolic syndrome (MetS) remains controversial. The objective of
      this study was to investigate the association and predictive ability of LDL-C
      with MetS. Methods: We analyzed the data from a population-based cross-sectional
      study conducted on representative samples of an Iranian adult population. The
      demographic data, anthropometric measures and the lipid profiles were measured
      with standard methods, and MetS was diagnosed by ATP III criteria. Logistic
      regression model and ROC analysis were used to estimate the predictive accuracy
      of LDL-C and its association with MetS. Results: The mean age (+/-SD) of
      participants with and without MetS was 47.6+/-12.5 years and 39.1+/-12.9 years,
      respectively (p=0.001). All anthropometric measures (body mass index, waist
      circumference, waist to hip ratio, waist to height ratio), systolic blood
      pressure, total cholesterol, triglycerides and fasting blood glucose were
      significantly higher in MetS, but a significantly higher difference in LDL-C was
      observed only in women. Accuracy of LDL-C in predicting MetS for men and women
      was 0.48 (95% CI: 0.43-0.54) and 0.55 (95% CI: 0.51-0.60), respectively. The
      unadjusted and adjusted odds ratios of different quartiles of LDL-C compared with
      1st quartile did not reach to a significant level. Conclusion: Serum LDL-C level
      is not significantly associated with MetS but exhibits a weak ability in
      predicting MetS in women.

PMID- 29201321
TI  - Efficacy of potassium polycitrate on renal stone and microlithiasis predisposed
      by metabolic disorders.
AB  - Background: According to high prevalence of renal stone in children, we evaluated
      the efficacy of treatment with potassium citrate and its correlation with
      metabolic disorders in children less than two years of age with renal stone and
      microlithiasis. Methods: In this cross- sectionaly study, 100 patients (less than
      2 years old) with renal stone or microlitiasis were evaluated for metabolic
      disorders. They were treated with potassium citrate and followed-up by
      ultrasonography every 3 months. Then response to treatment was evaluated
      according to the fresence metabolic disorders (A p-alue<0.05 was significant).
      Results: According to this study, hyperuricosuria and hypercalciuria were the two
      major metabolic disorders (40-33%). Seventy three patients had complete response,
      and also there as not a significant difference (p<0.05) in the efficacy of
      treatment due to types of metabolic disorders. There was significant difference
      between relative response to treatment in children who had metabolic disorders
      and patient without any metabolic disorders. Conclusion: Based on our results the
      use of potassium citrate in all children less than 2 years with renal stone or
      microlithiasis especially those with metabolic disorders, are recommended.

PMID- 29201322
TI  - The diagnostic value of fine needle aspiration in comparison with frozen section
      in thyroid nodules: A 20-year study.
AB  - Background: Fine needle aspiration (FNA) is the most important method in the
      diagnosis of thyroid nodules before surgery. Recently, the efficiency of FNA in
      thyroid nodule management has been debatable. On the other hand, intraoperative
      frozen section (FS) has been used to confirm the diagnosis of FNA and select the
      proper surgical approach. In this regard, the present study aimed to assess the
      diagnostic value of FNA as compared to FS in the diagnosis of thyroid nodules.
      Methods: This retrospective study was performed on 69 patients with FNA and FS
      and histopathological examination from 1993 to 2014 in Babol, northern Iran. FNA
      was classified into 5 groups: benign (colloid goiter), lymphocytic thyroiditis,
      follicular lesions, suspicious and malignant, and FS was classified as after
      benign or malignant. The results of both methods were compared with each other.
      Results: This retrospective study was performed on 69 patients with FNA and FS
      and histopathological examination from 1993 to 2014 in Babol, northern Iran. FNA
      was classified into 5 groups: benign (colloid goiter), lymphocytic thyroiditis,
      follicular lesions, suspicious and malignant, and FS was classified as after
      benign or malignant. The results of both methods were compared with each other.
      Conclusion: FNA was considered as a simple, less invasive and cost effective
      method with fewer side effects for evaluation of thyroid nodules. Particulary it
      had a high sensitivity and specificity in experienced and skilled hands.

PMID- 29201323
TI  - Does Serum lipid profile differ in anemia and non-anemic older subjects?
AB  - Background: There is some evidence that shows the symptoms of anemia are fewere
      in overweight and obese people, so, the purpose of this research was to study the
      relationship between anemia and iron deficiency anemia (IDA) with lipid profile
      status of the elderly. Methods: This cross-sectional study came from the Amirkola
      Health and Ageing Project (AHAP). A demographic questionnaire was given to the
      older people and a blood sample was obtained to assay their lipid indexes
      (triglyceride, cholesterol, HDL and LDL) and the parameters related to anemia
      after 12 hours fasting. The data were analyzed by chi-square test, t-test and
      Pearson correlation using SPSS. A p<0.05 was considered as the significance level
      of the tests. Results: The average age of the people was 68.95+/-7.43 years old.
      In this study, the prevalence of anemia and IDA was 31% and 9%, respectively. The
      mean concentration of serum triglyceride, cholesterol and LDL in the anemia group
      and the IDA group was less than the control groups. The amount of HDL in
      different groups was almost the same, although the difference was statistically
      significant with respect to variables like age and obesity (P=0.001). Conclusion:
      The study showed that the amount of lipid profile (triglyceride and cholesterol)
      in the elderly with anemia and IDA was less compared to other people. This result
      was achieved in some other research studies too, but further research is
      suggested to find possible mechanisms.

PMID- 29201324
TI  - Molecular characterization of Staphylococcus aureus strains isolated among
      hospital staff nasal carriers of Babol, Iran.
AB  - Background: Staphylococcus aureus (s. aureus) nasal carriers, particularly the
      healthcare staff can be considered as a potential source for the spread of
      resistant strains. The aim of this study was to determine the molecular
      characterization of S. aureus strains isolated among the staff nasal carriers in
      one of the teaching hospitals in Babol. Methods: A total of 120 nasal swabs were
      taken from the staff of Ayatollah Rouhani Hospital Babol during 2016. The
      antibiotic resistance pattern was performed by disc diffusion method for 13
      antibiotics, including cefoxitin, cephalothin, teicoplanin, vancomycin,
      daptomycin, oxacillin, amoxicillin, amikacin, linezolid, ciprofloxacin,
      levofloxacin, erythromycin, rifampin, according to the CLSI 2015. Polymerase
      chain reaction (PCR) was used to detect mecA and pvl genes. Finally, the
      different SCCmec types were determined by multiplex- PCR method. Results: Among
      the 120 collected specimens, 40(33.3%) S. aureus isolates were approved. 28(70%)
      of strains were identified as methicillin-resistant Staphylococcus aureus (MRSA)
      and the frequency of pvl gene was confirmed 2(5%). Based on the multiplex PCR
      assay, four different SCCmec types were detected as 35.7% type I, 14.2% type III,
      7.1% type II and 3.5% type IV. By a disc diffusion method, no resistance pattern
      was observed to vancomycin, while 100% of strains were resistant to amoxicillin.
      Conclusion: Consequently our results illustrated that isolated S. aureus strains
      among the staff nasal carriers via mentioned molecular characterization may lead
      to increase the nosocomial persistent infections in hospitalized patients and
      also health care workers.

PMID- 29201325
TI  - The association between Solar Lentigines and Type-2 Diabetes.
AB  - Background: Limited information exists between the associations of diabetes
      mellitus (DM) and solar lentigo (SL); a benign, common skin lesion characterized
      by hyperpigmented macules. Methods: This study was conducted on 90 patients
      diagnosed with DM and their age and sex matched controls who were referred to the
      Departments of Endocrinology at Babol University of Medical Science in Northern
      of Iran from January 2013 to December 2015. All demographic data including age,
      gender, occupation, family history of DM, estimated average sun exposure and
      presence of skin lesions were collected and analyzed. Results: Presence of SL was
      significantly higher among patients with DM compared to controls (61.9% vs 33.6%,
      P<0.001). After adjusting for age, sex and sun exposure rate, results indicated
      that DM was independently associated with the presence of SL (p=0.002).
      Stratifying patients based on gender, indicated that DM was significantly
      associated with SL in females (p=0.03), but not in male patients (p=0.06).
      Conclusion: The findings of the present study indicate that DM is an independent
      risk factor for the occurrence of SL lesions. These findings could represent a
      novel association between DM as a chronic oxidation state and SL as an early sign
      of aging.

PMID- 29201326
TI  - A challenging entity: multiple sclerosis or collagen tissue disorders: A case
      series of 6 patients.
AB  - Background: Multiple sclerosis and other demyelinating processes are sometimes
      difficult to differentiate from the neurological involvement in autoimmune
      diseases. Distinguishing multiple sclerosis from other lesions due to autoimmune
      diseases is crucial to avoid unsuitable or delayed treatments. Methods: Charts of
      6 patients diagnosed with mimicking multiple sclerosis between 1996 and 2014 were
      retrospectively assessed. Results: The mean age at diagnosis was 35+/-7 years.
      The most commonly neurological manifestation at onset was paraparesis due to
      transverse myelopathy and uni/bilateral optic neuropathy. All our patients
      suffered from recurrent episodes of optic neuritis with a mean lag time of 12
      months. Other initial presenting neurological manifestations in our patients
      included ataxic gait and pyramidal syndrome. Systemic symptoms occurred a long
      time before or after their initial neurological presentation. All patients had
      numerous T2 hyperintense lesions in the periventricular white matter and spinal
      cord with contrast enhancement. The antibodies tests revealed the presence of
      significant amounts of anti-nuclear antibodies. The anti-phospholipid antibodies
      were negative in all patients. All patients were treated with corticosteroid
      therapy and neurological features were cleared in all cases. Conclusion: Multiple
      sclerosis, other myelitis and optic neuritis, are sometimes difficult to
      differentiate from CNS involvement in autoimmune disease. Indeed, the clinical
      presentation, immunological profile and MRI lesions may be similar.

PMID- 29201327
TI  - Stiff person case misdiagnosed as conversion disorder: A case report.
AB  - Background: Stiff person syndrome (SPS) is a rare neurological disease resulting
      in stiffness and spasm of muscles. It initially affects the axial muscles and
      then spread to limb muscles. Emotional stress exacerbated the symptoms and signs
      of the disease. The pathophysiology of the disease is caused by the decreased
      level of the glutamic acid decarboxylase (GAD) activity due to an autoantibody
      against GAD that decreases the level of gamma-aminobutyric acid (GABA). In this
      paper, we present a case of atypical presentation of SPS with lower limb
      stiffness misdiagnosed as conversion disorder. Case presentation: We report a
      patient with atypical presentation of SPS with lower limb stiffness and gait
      disorder misdiagnosed as conversion disorder for a year. Her antithyroid
      peroxidase antibody (anti-TPO Ab) level was 75 IU (normal value: 0-34 IU).
      Intravenous immunoglobulin (IVIG) was administered (2gr/kg, 5 days) for the
      patient that showed significant improvement in the follow-up visit. Conclusion:
      It is essential that in any patient with bizarre gait disorder and suspicious to
      conversion disorder due to the reversibility of symptoms, SPS and other movement
      disorder should be considered.

PMID- 29201328
TI  - Hughes-Stovin syndrome revealing the presence of Behcet's Disease.
AB  - Background: Hughes-Stovin Syndrome (HSS) is a rare clinical disorder
      characterized by deep venous thrombosis and multiple pulmonary and/or bronchial
      aneurysms. Aneurysms in systemic circulation can also be seen. Case presentation:
      We report the first case of HSS with aortic aneurysm in a 55-year-old man who
      initially presented with deep venous thrombosis. The diagnosis of HSS revealing
      Behcet's disease was made given the history of recurrent oral and genital ulcers.
      Treatment consisted of 3 daily pulses of methylprednisolone (1g) followed by oral
      prednisone (1mg/kg daily) and 6 monthly pulses of cyclophosphamide. Oral
      anticoagulation treatment was held 3 months and then was stopped with good
      outcome. Conclusion: Systemic aneurysms in Hughes Stovin is a worth knowing
      complication which may reveal Behcet's disease.

PMID- 29201329
TI  - Internet-based support system and rehabilitation of drug users under maintenance
      treatment.

PMID- 29201330
TI  - Frame-Based CT Image Reconstruction via the Balanced Approach.
AB  - Frame-based regularization method as one kind of sparsity representation method
      has been developed in recent years and has been proved to be an efficient method
      for CT image reconstruction. However, most of the developed CT image
      reconstruction methods are analysis-based frame methods. This paper proposes a
      novel frame-based balanced hybrid model with two sparse regularization terms for
      CT image reconstruction. We generalize the fast alternating direction method to
      solve the proposed model so that every subproblem can be easily solved. The
      numerical experiments suggest that the proposed hybrid balanced-based wavelet
      regularization scheme is efficient in terms of reducing the defined
      reconstruction root mean squared error and improving the signal to noise ratio in
      CT image reconstruction.

PMID- 29201331
TI  - Determination of Fetal Left Ventricular Volume Based on Two-Dimensional
      Echocardiography.
AB  - Determination of fetal left ventricular (LV) volume in two-dimensional
      echocardiography (2DE) is significantly important for quantitative analysis of
      fetal cardiac function. A backpropagation (BP) neural network method is proposed
      to predict LV volume more accurately and effectively. The 2DE LV border and
      volume are considered as the input and output of BP neural network
      correspondingly. To unify and simplify the input of the BP neural network, 16
      distances calculated from the border to its center with equal angle are used
      instead of the border. Fifty cases (forty frames for each) were used for this
      study. Half of them selected randomly are used for training, and the others are
      used for testing. To illustrate the performance of BP neural network, area-length
      method, Simpson's method, and multivariate nonlinear regression equation method
      were compared by comparisons with the volume references in concordance
      correlation coefficient (CCC), intraclass correlation coefficient (ICC), and
      Bland-Altman plots. The ICC and CCC for BP neural network with the volume
      references were the highest. For Bland-Altman plots, the BP neural network also
      shows the highest agreement and reliability with volume references. With the
      accurate LV volume, LV function parameters (stroke volume (SV) and ejection
      fraction (EF)) are calculated accurately.

PMID- 29201332
TI  - An Improved Random Walker with Bayes Model for Volumetric Medical Image
      Segmentation.
AB  - Random walk (RW) method has been widely used to segment the organ in the
      volumetric medical image. However, it leads to a very large-scale graph due to a
      number of nodes equal to a voxel number and inaccurate segmentation because of
      the unavailability of appropriate initial seed point setting. In addition, the
      classical RW algorithm was designed for a user to mark a few pixels with an
      arbitrary number of labels, regardless of the intensity and shape information of
      the organ. Hence, we propose a prior knowledge-based Bayes random walk framework
      to segment the volumetric medical image in a slice-by-slice manner. Our strategy
      is to employ the previous segmented slice to obtain the shape and intensity
      knowledge of the target organ for the adjacent slice. According to the prior
      knowledge, the object/background seed points can be dynamically updated for the
      adjacent slice by combining the narrow band threshold (NBT) method and the organ
      model with a Gaussian process. Finally, a high-quality image segmentation result
      can be automatically achieved using Bayes RW algorithm. Comparing our method with
      conventional RW and state-of-the-art interactive segmentation methods, our
      results show an improvement in the accuracy for liver segmentation (p < 0.001).

PMID- 29201333
TI  - Development of the Arabic Voice Pathology Database and Its Evaluation by Using
      Speech Features and Machine Learning Algorithms.
AB  - A voice disorder database is an essential element in doing research on automatic
      voice disorder detection and classification. Ethnicity affects the voice
      characteristics of a person, and so it is necessary to develop a database by
      collecting the voice samples of the targeted ethnic group. This will enhance the
      chances of arriving at a global solution for the accurate and reliable diagnosis
      of voice disorders by understanding the characteristics of a local group.
      Motivated by such idea, an Arabic voice pathology database (AVPD) is designed and
      developed in this study by recording three vowels, running speech, and isolated
      words. For each recorded samples, the perceptual severity is also provided which
      is a unique aspect of the AVPD. During the development of the AVPD, the
      shortcomings of different voice disorder databases were identified so that they
      could be avoided in the AVPD. In addition, the AVPD is evaluated by using six
      different types of speech features and four types of machine learning algorithms.
      The results of detection and classification of voice disorders obtained with the
      sustained vowel and the running speech are also compared with the results of an
      English-language disorder database, the Massachusetts Eye and Ear Infirmary
      (MEEI) database.

PMID- 29201334
TI  - Navigating the choice of oral anticoagulation therapy for atrial fibrillation in
      the NOAC era.
AB  - Atrial fibrillation (AF) is a major cause of ischaemic stroke. The majority of
      these strokes can be prevented by treatment with oral anticoagulation therapy.
      The advent of non-vitamin K antagonist oral anticoagulants (NOACs) has resulted
      in a choice of therapeutic agents available to physicians for anticoagulation for
      stroke prevention in patients with AF beyond the long-established vitamin K
      antagonists (VKAs). Pivotal trials have demonstrated non-inferiority of NOACs
      compared with VKAs, and in some cases superiority, for the prevention of stroke
      and systemic embolism in non-valvular AF. Yet there are no direct head-to-head
      comparator trials for the efficacy of NOACs. Therefore, the question of which
      oral anticoagulant for each individual patient can present a challenge to
      physicians. In this review article, we assess which patients with AF require
      anticoagulation, review the available therapeutic options, assessing the evidence
      base for each and offering guidance as to patient-specific factors that can
      influence this choice.

PMID- 29201335
TI  - Peripheral Visual Cues Contribute to the Perception of Object Movement During
      Self-Movement.
AB  - Safe movement through the environment requires us to monitor our surroundings for
      moving objects or people. However, identification of moving objects in the scene
      is complicated by self-movement, which adds motion across the retina. To identify
      world-relative object movement, the brain thus has to 'compensate for' or 'parse
      out' the components of retinal motion that are due to self-movement. We have
      previously demonstrated that retinal cues arising from central vision contribute
      to solving this problem. Here, we investigate the contribution of peripheral
      vision, commonly thought to provide strong cues to self-movement. Stationary
      participants viewed a large field of view display, with radial flow patterns
      presented in the periphery, and judged the trajectory of a centrally presented
      probe. Across two experiments, we demonstrate and quantify the contribution of
      peripheral optic flow to flow parsing during forward and backward movement.

PMID- 29201336
TI  - Social Factors in Aesthetics: Social Conformity Pressure and a Sense of Being
      Watched Affect Aesthetic Judgments.
AB  - The present study is a first attempt to experimentally test the impact of two
      specific social factors, namely social conformity pressure and a sense of being
      watched, on participants' judgments of the artistic quality of aesthetic objects.
      We manipulated conformity pressure with a test form in which a photograph of each
      stimulus was presented together with unanimously low (downward pressure) or high
      quality ratings (upward pressure) of three would-be previous raters.
      Participants' sense of being watched was manipulated by testing each of them in
      two settings, one of which contained an eyespots stimulus. Both social factors
      significantly affected the participants' judgments-unexpectedly, however, with
      conformity pressure only working in the downward direction and eyespots leading
      to an overall downward shift in participants' judgments. Our findings indicate
      the relevance of including explicit and implicit social factors in aesthetics
      research, thus also reminding us of the limitations of overly reductionist
      approaches to investigating aesthetic perception and experience.

PMID- 29201337
TI  - Defocus Discrimination in Video: Motion in Depth.
AB  - We perform two psychophysics experiments to investigate a viewer's ability to
      detect defocus in video; in particular, the defocus that arises in video during
      motion in depth when the camera does not maintain sharp focus throughout the
      motion. The first experiment demonstrates that blur sensitivity during viewing is
      affected by the speed at which the target moves towards the camera. The second
      experiment measures a viewer's ability to notice momentary defocus and shows that
      the threshold of blur detection in arc minutes decreases significantly as the
      duration of the blur increases. Our results suggest that it is important to have
      good control of focus while recording video and that momentary defocus should be
      kept as short as possible so it goes unnoticed.

PMID- 29201338
TI  - Moving Backgrounds Massively Change the Apparent Size, Shape and Orientation of
      Flashed Test Squares.
AB  - A random-dot background was expanded and contracted, and rotated, or expanded in
      one dimension while contracting on the other, or skewed back and forth
      horizontally. Squares that were flashed at the reversal points of these affine
      pattern distortions, aligned to edges in the texture, showed massive changes in
      size and shape.

PMID- 29201339
TI  - Trigger Features for Conveying Facial Expressions: The Role of Segmentation.
AB  - Primates are especially good at recognizing facial expression using two
      contrasting strategies-an individual diagnostic feature (e.g., raise eyebrows or
      lower mouth corner) versus a relationship between features. We report several
      novel experiments that demonstrate a profound role of grouping and segmentation
      including stereo-on recognition of facial expressions.

PMID- 29201341
TI  - Depth Without a Surface: Observations From a "Finger Spinner" Depth Illusion.
AB  - A trending novelty toy that is spun between the fingers induces a striking depth
      illusion from specular reflections. Further examination of the phenomenon
      suggests that when surface features are obscured by spinning, depth from
      disparity of reflections is enhanced.

PMID- 29201340
TI  - 50 Years of Stereoblindness: Reconciliation of a Continuum of Disparity Detectors
      With Blindness for Disparity in Near or Far Depth.
AB  - Whitman Richards (1932-2016) discovered some 50 years ago that about 30% of
      observers from the normal population exhibit stereoblindness: the disability to
      process binocular disparities in either far or near depth. We review the
      literature on stereoblindness entailing two insights. First, contemporary
      scholars in stereopsis undervalue the comprehension that disparity processing
      studies require precise assessments of observers' stereoblindness. We argue that
      this frequently leads to suboptimal interpretations. Second, there is still an
      open conundrum: How can the established finding that disparity is processed by a
      continuum of detectors be reconciled with the disability of many observers to
      process a whole class of far or near disparities? We propose, based upon
      integration of literature, that an asymmetry between far and near disparity
      detection at birth-being present for a variety of reasons-can suppress the
      typical formation of binocular correlation during the critical period for the
      development of stereopsis early in life, thereby disabling a whole class of far
      or near disparities.

PMID- 29201342
TI  - A SMARC Effect for Loudness.
AB  - Various reports suggest that the pitch height of musical tones may be represented
      along a mental space, with lower pitch heights represented on the left or lower
      sectors and higher pitch heights represented on the right or upper sectors of the
      mental space. Given that in Western languages the loudness of tones is often
      addressed spatially, with loud sounds referred to as "high" and quiet sounds
      referred to as "low," here we investigated whether loudness might also have a
      spatial representation. Participants judged whether a tone was louder or quieter
      than a reference tone, by pressing two keys: one at the top and the other at the
      bottom of a response box. Participants were faster in a situation where they
      pressed the key at the top to report louder sounds, and the key at the bottom to
      report quieter sounds, than vice versa. This result supports the view that
      loudness, like other types of magnitudes, might be represented spatially.

PMID- 29201343
TI  - The evolutionary origin of digit patterning.
AB  - The evolution of tetrapod limbs from paired fins has long been of interest to
      both evolutionary and developmental biologists. Several recent investigative
      tracks have converged to restructure hypotheses in this area. First, there is now
      general agreement that the limb skeleton is patterned by one or more Turing-type
      reaction-diffusion, or reaction-diffusion-adhesion, mechanism that involves the
      dynamical breaking of spatial symmetry. Second, experimental studies in finned
      vertebrates, such as catshark and zebrafish, have disclosed unexpected
      correspondence between the development of digits and the development of both the
      endoskeleton and the dermal skeleton of fins. Finally, detailed mathematical
      models in conjunction with analyses of the evolution of putative Turing system
      components have permitted formulation of scenarios for the stepwise evolutionary
      origin of patterning networks in the tetrapod limb. The confluence of
      experimental and biological physics approaches in conjunction with deepening
      understanding of the developmental genetics of paired fins and limbs has moved
      the field closer to understanding the fin-to-limb transition. We indicate
      challenges posed by still unresolved issues of novelty, homology, and the
      relation between cell differentiation and pattern formation.

PMID- 29201344
TI  - Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and
      pharmacodynamic effects in their potentially additive nature.
AB  - Background: Whether arrhythmia risks will increase if drugs with
      electrocardiographic (ECG) QT-prolonging properties are combined is generally
      supposed but not well studied. Based on available evidence, the Arizona Center
      for Education and Research on Therapeutics (AZCERT) classification defines the
      risk of QT prolongation for exposure to single drugs. We aimed to investigate how
      combining AZCERT drug categories impacts QT duration and how relative drug
      exposure affects the extent of pharmacodynamic drug-drug interactions. Methods:
      In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether
      AZCERT class and number of coprescribed QT-prolonging drugs correlates with
      observed rate-corrected QT duration (QTc) while also considering age, sex,
      inpatient status, and other QTc-prolonging risk factors. We concurrently
      considered administered drug doses and pharmacokinetic interactions modulating
      drug clearance to calculate individual weights of relative exposure with AZCERT
      drugs. Because QTc duration is concentration-dependent, we estimated individual
      drug exposure with these drugs and included this information as weights in
      weighted regression analyses. Results: Drugs attributing a 'known' risk for
      clinical consequences were associated with the largest QTc prolongations.
      However, the presence of at least two versus one QTc-prolonging drug yielded
      nonsignificant prolongations [exposure-weighted parameter estimates with 95%
      confidence intervals for 'known' risk drugs + 0.93 ms (-8.88;10.75)]. Estimates
      for the 'conditional' risk class increased upon refinement with relative drug
      exposure and co-administration of a 'known' risk drug as a further risk factor.
      Conclusions: These observations indicate that indiscriminate combinations of QTc
      prolonging drugs do not necessarily result in additive QTc prolongation and
      suggest that QT prolongation caused by drug combinations strongly depends on the
      nature of the combination partners and individual drug exposure. Concurrently, it
      stresses the value of the AZCERT classification also for the risk prediction of
      combination therapies with QT-prolonging drugs.

PMID- 29201345
TI  - Sensitization to PR-10 proteins is indicative of distinctive sensitization
      patterns in adults with a suspected food allergy.
AB  - Background: The extent of co-sensitization within and between food protein
      families in an adult population is largely unknown. This study aimed to identify
      the most frequently recognized components in the PR-10 and storage protein
      family, as well as patterns in (co-)sensitization, in a birch-endemic area.
      Methods: Results of ImmunoCAP ISAC, performed during routine care in Dutch adult
      outpatients suspected of food allergy, were collected. Results: A total of 305
      patients were selected, aged 16-79 years (median 32 years). Sensitization to one
      or more PR-10 proteins was most frequent (74% of all subjects), followed by 35%
      to storage protein and 15% to nsLTPs. Within the PR-10 family, subjects were most
      often sensitized to Bet v 1 (73% of 305), Cor a 1.04 (72%) and Mal d 1 (68%).
      Sensitization to PR-10s from soy, celery and kiwi occurred distinctively less
      often (< 55% of Bet v 1 sensitized subjects) compared to other food PR-10s (all >
      70%). Subjects sensitized to these 'less common PR-10 proteins' were sensitized
      to more food and inhalant components on the ISAC, compared to subjects sensitized
      to 'common PR-10 proteins' (median 22 vs 13 out of 112, p < 0.0001). Seven
      subjects demonstrated sensitization to food PR-10 proteins, without concomitant
      sensitization to pollen PR-10s. Within the storage proteins, sensitization to
      multiple peanut allergens was most common (on average 3 out of 4). Conclusions:
      Sensitization to PR-10 food proteins could occur without concomitant
      sensitization to common PR-10 from pollen in a subset of subjects. Less commonly
      recognized PR-10 proteins appear to be an indication of polysensitization.

PMID- 29201347
TI  - The creation and evaluation of a model to simulate the probability of conception
      in seasonal-calving pasture-based dairy heifers.
AB  - Background: Herd fertility in pasture-based dairy farms is a key driver of farm
      economics. Models for predicting nulliparous reproductive outcomes are rare, but
      age, genetics, weight, and BCS have been identified as factors influencing heifer
      conception. The aim of this study was to create a simulation model of heifer
      conception to service with thorough evaluation. Methods: Artificial Insemination
      service records from two research herds and ten commercial herds were provided to
      build and evaluate the models. All were managed as spring-calving pasture-based
      systems. The factors studied were related to age, genetics, and time of service.
      The data were split into training and testing sets and bootstrapping was used to
      train the models. Logistic regression (with and without random effects) and
      generalised additive modelling were selected as the model-building techniques.
      Two types of evaluation were used to test the predictive ability of the models:
      discrimination and calibration. Discrimination, which includes sensitivity,
      specificity, accuracy and ROC analysis, measures a model's ability to distinguish
      between positive and negative outcomes. Calibration measures the accuracy of the
      predicted probabilities with the Hosmer-Lemeshow goodness-of-fit, calibration
      plot and calibration error. Results: After data cleaning and the removal of
      services with missing values, 1396 services remained to train the models and 597
      were left for testing. Age, breed, genetic predicted transmitting ability for
      calving interval, month and year were significant in the multivariate models. The
      regression models also included an interaction between age and month. Year within
      herd was a random effect in the mixed regression model. Overall prediction
      accuracy was between 77.1% and 78.9%. All three models had very high sensitivity,
      but low specificity. The two regression models were very well-calibrated. The
      mean absolute calibration errors were all below 4%. Conclusion: Because the
      models were not adept at identifying unsuccessful services, they are not
      suggested for use in predicting the outcome of individual heifer services.
      Instead, they are useful for the comparison of services with different covariate
      values or as sub-models in whole-farm simulations. The mixed regression model was
      identified as the best model for prediction, as the random effects can be ignored
      and the other variables can be easily obtained or simulated.

PMID- 29188012
TI  - Creating, generating and comparing random network models with NetworkRandomizer.
AB  - Biological networks are becoming a fundamental tool for the investigation of high
      throughput data in several fields of biology and biotechnology. With the
      increasing amount of information, network-based models are gaining more and more
      interest and new techniques are required in order to mine the information and to
      validate the results. To fill the validation gap we present an app, for the
      Cytoscape platform, which aims at creating randomised networks and randomising
      existing, real networks. Since there is a lack of tools that allow performing
      such operations, our app aims at enabling researchers to exploit different, well
      known random network models that could be used as a benchmark for validating
      real, biological datasets. We also propose a novel methodology for creating
      random weighted networks, i.e. the multiplication algorithm, starting from real,
      quantitative data. Finally, the app provides a statistical tool that compares
      real versus randomly computed attributes, in order to validate the numerical
      findings. In summary, our app aims at creating a standardised methodology for the
      validation of the results in the context of the Cytoscape platform.

PMID- 29188012
TI  - Creating, generating and comparing random network models with NetworkRandomizer.
AB  - Biological networks are becoming a fundamental tool for the investigation of high
      throughput data in several fields of biology and biotechnology. With the
      increasing amount of information, network-based models are gaining more and more
      interest and new techniques are required in order to mine the information and to
      validate the results. To fill the validation gap we present an app, for the
      Cytoscape platform, which aims at creating randomised networks and randomising
      existing, real networks. Since there is a lack of tools that allow performing
      such operations, our app aims at enabling researchers to exploit different, well
      known random network models that could be used as a benchmark for validating
      real, biological datasets. We also propose a novel methodology for creating
      random weighted networks, i.e. the multiplication algorithm, starting from real,
      quantitative data. Finally, the app provides a statistical tool that compares
      real versus randomly computed attributes, in order to validate the numerical
      findings. In summary, our app aims at creating a standardised methodology for the
      validation of the results in the context of the Cytoscape platform.

PMID- 29188013
TI  - Scaling-up primary health care-based prevention and management of alcohol use
      disorder at the municipal level in middle-income countries in Latin America:
      Background and pre-protocol for a three-country quasi-experimental study.
AB  - Background: While primary health care (PHC)-based prevention and management of
      alcohol use disorder (AUD) is clinically effective and cost-effective, it remains
      poorly implemented in routine practice. Systematic reviews and multi-country
      studies have demonstrated the ability of training and support programmes to
      increase PHC-based screening and brief advice activity to reduce heavy drinking.
      However, gains have been only modest and short term at best. WHO studies have
      concluded that a more effective uptake could be achieved by embedding PHC
      activity within broader community and municipal support.  Protocol: A quasi
      experimental study will compare PHC-based prevention and management of AUD,
      operationalized by heavy drinking, in three intervention cities from Colombia,
      Mexico and Peru with three comparator cities from the same countries. In the
      implementation cities, primary health care units (PHCUs) will receive training
      embedded within ongoing supportive municipal action over an 18-month
      implementation period. In the comparator cities, practice as usual will continue
      at both municipal and PHCU levels. The primary outcome will be the proportion of
      consulting adult patients intervened with (screened and advice given to screen
      positives). The study is powered to detect a doubling of the outcome measure from
      an estimated 2.5/1,000 patients at baseline. Formal evaluation points will be at
      baseline, mid-point and end-point of the 18-month implementation period. We will
      present the ratio (plus 95% confidence interval) of the proportion of patients
      receiving intervention in the implementation cities with the proportions in the
      comparator cities. Full process evaluation will be undertaken, coupled with an
      analysis of potential contextual, financial and political-economy influencing
      factors.  Discussion: This multi-country study will test the extent to which
      embedding PHC-based prevention and management of alcohol use disorder with
      supportive municipal action leads to improved scale-up of more patients with
      heavy drinking receiving appropriate advice and treatment.

PMID- 29188014
TI  - Assessment of injection safety in Ha Dong General Hospital, Hanoi, in 2012.
AB  - Background: Injection is one of the most frequently used medical methods to
      introduce drugs or other substances into the body for purposes of treatment or
      prevention. Unsafe injection can cause adverse outcomes, such as abscess and
      anaphylactic shock, and increases the risk of blood-borne transmission of viruses
      to patients and health care workers, as well as the community. Recognizing the
      importance of injection safety, in 2000 the Vietnamese Ministry of Health (MOH)
      collaborated with the Vietnam Nurses Association to launch the "Safe injection"
      program throughout the country, including Hanoi. Methods: This cross-sectional
      study, combining quantitative and qualitative analysis, was conducted from
      February to August 2012 in Ha Dong General Hospital using a structured
      questionnaire and observation checklist. The target population of the study was
      109 nurses working in clinical departments and 436 injections were observed.
      Results: The percentage of nurses who are familiar with injection safety
      standards was found to be 82.6%. The proportion of practical injections that met
      the 23 standards of injection safety set by the MOH amounted to 22.2%. The
      factors related to safe injection practice of nurses who are younger age group
      (OR=3.1; p<0.05) and lower amount of working years (OR=2.8; p<0.05). Conclusions:
      Despite the high level of knowledge about safety injection, a low proportion of
      nurses performed correct safety injection practice. Moreover, the results
      demonstrated that experience might not always guarantee better practice. The
      findings raise the need for further training about this issue, especially among
      older nurses.

PMID- 29201346
TI  - The chiropractic profession: a scoping review of utilization rates, reasons for
      seeking care, patient profiles, and care provided.
AB  - Background: Previous research has investigated utilization rates, who sees
      chiropractors, for what reasons, and the type of care that chiropractors provide.
      However, these studies have not been comprehensively synthesized. We aimed to
      give a global overview by summarizing the current literature on the utilization
      of chiropractic services, reasons for seeking care, patient profiles, and
      assessment and treatment provided. Methods: Systematic searches were conducted in
      MEDLINE, CINAHL, and Index to Chiropractic Literature using keywords and subject
      headings (MeSH or ChiroSH terms) from database inception to January 2016.
      Eligible studies: 1) were published in English or French; 2) were case series,
      descriptive, cross-sectional, or cohort studies; 3) described patients receiving
      chiropractic services; and 4) reported on the following theme(s): utilization
      rates of chiropractic services; reasons for attending chiropractic care; profiles
      of chiropractic patients; or, types of chiropractic services provided. Paired
      reviewers independently screened all citations and data were extracted from
      eligible studies. We provided descriptive numerical analysis, e.g. identifying
      the median rate and interquartile range (e.g., chiropractic utilization rate)
      stratified by study population or condition. Results: The literature search
      retrieved 14,149 articles; 328 studies (reported in 337 articles) were relevant
      and reported on chiropractic utilization (245 studies), reason for attending
      chiropractic care (85 studies), patient demographics (130 studies), and
      assessment and treatment provided (34 studies). Globally, the median 12-month
      utilization of chiropractic services was 9.1% (interquartile range (IQR): 6.7%
      13.1%) and remained stable between 1980 and 2015. Most patients consulting
      chiropractors were female (57.0%, IQR: 53.2%-60.0%) with a median age of 43.4
      years (IQR: 39.6-48.0), and were employed (median: 77.3%, IQR: 70.3%-85.0%). The
      most common reported reasons for people attending chiropractic care were (median)
      low back pain (49.7%, IQR: 43.0%-60.2%), neck pain (22.5%, IQR: 16.3%-24.5%), and
      extremity problems (10.0%, IQR: 4.3%-22.0%). The most common treatment provided
      by chiropractors included (median) spinal manipulation (79.3%, IQR: 55.4%-91.3%),
      soft-tissue therapy (35.1%, IQR: 16.5%-52.0%), and formal patient education
      (31.3%, IQR: 22.6%-65.0%). Conclusions: This comprehensive overview on the world
      wide state of the chiropractic profession documented trends in the literature
      over the last four decades. The findings support the diverse nature of
      chiropractic practice, although common trends emerged.

PMID- 29188014
TI  - Assessment of injection safety in Ha Dong General Hospital, Hanoi, in 2012.
AB  - Background: Injection is one of the most frequently used medical methods to
      introduce drugs or other substances into the body for purposes of treatment or
      prevention. Unsafe injection can cause adverse outcomes, such as abscess and
      anaphylactic shock, and increases the risk of blood-borne transmission of viruses
      to patients and health care workers, as well as the community. Recognizing the
      importance of injection safety, in 2000 the Vietnamese Ministry of Health (MOH)
      collaborated with the Vietnam Nurses Association to launch the "Safe injection"
      program throughout the country, including Hanoi. Methods: This cross-sectional
      study, combining quantitative and qualitative analysis, was conducted from
      February to August 2012 in Ha Dong General Hospital using a structured
      questionnaire and observation checklist. The target population of the study was
      109 nurses working in clinical departments and 436 injections were observed.
      Results: The percentage of nurses who are familiar with injection safety
      standards was found to be 82.6%. The proportion of practical injections that met
      the 23 standards of injection safety set by the MOH amounted to 22.2%. The
      factors related to safe injection practice of nurses who are younger age group
      (OR=3.1; p<0.05) and lower amount of working years (OR=2.8; p<0.05). Conclusions:
      Despite the high level of knowledge about safety injection, a low proportion of
      nurses performed correct safety injection practice. Moreover, the results
      demonstrated that experience might not always guarantee better practice. The
      findings raise the need for further training about this issue, especially among
      older nurses.

PMID- 29188013
TI  - Scaling-up primary health care-based prevention and management of heavy drinking
      at the municipal level in middle-income countries in Latin America: Background
      and protocol for a three-country quasi-experimental study.
AB  - Background: While primary health care (PHC)-based prevention and management of
      heavy drinking is clinically effective and cost-effective, it remains poorly
      implemented in routine practice. Systematic reviews and multi-country studies
      have demonstrated the ability of training and support programmes to increase PHC
      based screening and brief advice activity to reduce heavy drinking. However,
      gains have been only modest and short term at best. WHO studies have concluded
      that a more effective uptake could be achieved by embedding PHC activity within
      broader community and municipal support. Protocol: A quasi-experimental study
      will compare PHC-based prevention and management of heavy drinking in three
      intervention cities from Colombia, Mexico and Peru with three comparator cities
      from the same countries. In the implementation cities, primary health care units
      (PHCUs) will receive training embedded within ongoing supportive municipal action
      over an 18-month implementation period. In the comparator cities, practice as
      usual will continue at both municipal and PHCU levels. The primary outcome will
      be the proportion of consulting adult patients intervened with (screened and
      advice given to screen positives). The study is powered to detect a doubling of
      the outcome measure from an estimated 2.5/1,000 patients at baseline. Formal
      evaluation points will be at baseline, mid-point and end-point of the 18-month
      implementation period. We will present the ratio (plus 95% confidence interval)
      of the proportion of patients receiving intervention in the implementation cities
      with the proportions in the comparator cities. Full process evaluation will be
      undertaken, coupled with an analysis of potential contextual, financial and
      political-economy influencing factors. Discussion: This multi-country study will
      test the extent to which embedding PHC-based prevention and management of alcohol
      use disorder with supportive municipal action leads to improved scale-up of more
      patients with heavy drinking receiving appropriate advice and treatment. Study
      status: The four-year study will start on 1 st December 2017.

PMID- 29188016
TI  - An analysis of characteristics of post-authorisation studies registered on the
      ENCePP EU PAS Register.
AB  - Background: The objective of this study was to investigate the study design
      characteristics of Post-Authorisation Studies (PAS) requested by the European
      Medicines Agency which were recorded on the European Union (EU) PAS Register held
      by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance
      (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all
      studies registered on the EU PAS Register as of 18 th October 2016. Results: We
      identified a total of 314 studies on the EU PAS Register, including 81 (26%)
      finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified,
      205 (65%) included risk assessment in their scope, 133 (42%) included drug
      utilisation and 94 (30%) included effectiveness evaluation. Just over half of the
      studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4
      (1%) used a hybrid design combining both approaches. Risk assessment and
      effectiveness studies were more likely to use primary data capture (60% and 85%
      respectively as compared to 39% and 14% respectively for secondary). The converse
      was true for drug utilisation studies where 59% were secondary vs. 39% for
      primary. For type 2 diabetes mellitus, database studies were more commonly used
      (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs)
      whereas for studies in oncology, primary data capture were more likely to be used
      (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of
      this analysis show that PAS design varies according to study objectives and
      therapeutic area.

PMID- 29188018
TI  - Moderate-to-severe atopic dermatitis patients show increases in serum C-reactive
      protein levels, correlating with skin disease activity.
AB  - Background: Atopic dermatitis (AD), the most common chronic inflammatory skin
      disease, is evolving as a systemic disease, and associated systemic inflammation
      is possibly linked to increases in cardiovascular disease. Methods: We assessed
      levels of the inflammatory marker CRP in 59 patients with moderate-to-severe AD
      compared to matched healthy controls, and to determine correlation with skin
      disease severity. Clinical severity was measured using SCORing of Atopic
      Dermatitis (SCORAD) and body surface area (BSA). Control subjects (n=118),
      matched by age, gender, smoking status and ethnicity, were obtained from the
      National Health and Nutrition Survey (NHANES). Results: AD patients had
      significantly increased serum CRP levels compared to controls (0.7+/-1.0 vs.
      0.4+/-0.7mg/dl; p=0.001), and 52.5% of them showed CRP levels >0.3mg/dl,
      predicting high cardiovascular risk. CRP levels were significantly correlated
      with both SCORAD (r=0.427, p=0.0008) and BSA (r=0.407, p=0.0015).  IgE levels in
      AD were highly elevated (median 2903U/ml, IQR [234,10655]), but only weakly
      correlated with SCORAD (r=0.282, p=0.0427) and BSA (r=0.382, p=0.0052), but not
      with CRP levels. AD patients also showed increased LDH levels, but without
      significant correlations with disease severity (SCORAD, BSA) or CRP. Conclusions:
      Our study strongly supports CRP as a marker for disease severity in moderate-to
      severe AD patients, further demonstrating its chronic systemic nature.

PMID- 29188015
TI  - A multi-disciplinary perspective on emergent and future innovations in peer
      review.
AB  - Peer review of research articles is a core part of our scholarly communication
      system. In spite of its importance, the status and purpose of peer review is
      often contested. What is its role in our modern digital research and
      communications infrastructure? Does it perform to the high standards with which
      it is generally regarded? Studies of peer review have shown that it is prone to
      bias and abuse in numerous dimensions, frequently unreliable, and can fail to
      detect even fraudulent research. With the advent of web technologies, we are now
      witnessing a phase of innovation and experimentation in our approaches to peer
      review. These developments prompted us to examine emerging models of peer review
      from a range of disciplines and venues, and to ask how they might address some of
      the issues with our current systems of peer review. We examine the functionality
      of a range of social Web platforms, and compare these with the traits underlying
      a viable peer review system: quality control, quantified performance metrics as
      engagement incentives, and certification and reputation. Ideally, any new systems
      will demonstrate that they out-perform and reduce the biases of existing models
      as much as possible. We conclude that there is considerable scope for new peer
      review initiatives to be developed, each with their own potential issues and
      advantages. We also propose a novel hybrid platform model that could, at least
      partially, resolve many of the socio-technical issues associated with peer
      review, and potentially disrupt the entire scholarly communication system.
      Success for any such development relies on reaching a critical threshold of
      research community engagement with both the process and the platform, and
      therefore cannot be achieved without a significant change of incentives in
      research environments.

PMID- 29201357
TI  - Human S100A5 binds Ca2+ and Cu2+ independently.
AB  - Background: S100A5 is a calcium binding protein found in a small subset of
      amniote tissues. Little is known about the biological roles of S100A5, but it may
      be involved in inflammation and olfactory signaling. Previous work indicated that
      S100A5 displays antagonism between binding of Ca2+ and Cu2+ ions-one of the most
      commonly cited features of the protein. We set out to characterize the interplay
      between Ca2+ and Cu2+ binding by S100A5 using isothermal titration calorimetry
      (ITC), circular dichroism spectroscopy (CD), and analytical ultracentrifugation
      (AUC). Results: We found that human S100A5 is capable of binding both Cu2+ and
      Ca2+ ions simultaneously. The wildtype protein was extremely aggregation-prone in
      the presence of Cu2+ and Ca2+. A Cys-free version of S100A5, however, was not
      prone to precipitation or oligomerization. Mutation of the cysteines does not
      disrupt the binding of either Ca2+ or Cu2+ to S100A5. In the Cys-free background,
      we measured Ca2+ and Cu2+ binding in the presence and absence of the other metal
      using ITC. Saturating concentrations of Ca2+ or Cu2+ do not disrupt the binding
      of one another. Ca2+ and Cu2+ binding induce structural changes in S100A5, which
      are measurable using CD spectroscopy. We show via sedimentation velocity AUC that
      the wildtype protein is prone to the formation of soluble oligomers, which are
      not present in Cys-free samples. Conclusions: S100A5 can bind Ca2+ and Cu2+ ions
      simultaneously and independently. This observation is in direct contrast to
      previously-reported antagonism between binding of Cu2+ and Ca2+ ions. The
      previous result is likely due to metal-dependent aggregation. Little is known
      about the biology of S100A5, so an accurate understanding of the biochemistry is
      necessary to make informed biological hypotheses. Our observations suggest the
      possibility of independent biological functions for Cu2+ and Ca2+ binding by
      S100A5.

PMID- 29201358
TI  - Association of postoperative nausea/vomiting and pain with breastfeeding success.
AB  - Background: Successful breastfeeding is a goal set forth by the World Health
      Organization to improve neonatal care. Increasingly, patients express the desire
      to breastfeed, and clinicians should facilitate successful breastfeeding. The
      primary aim of this study is to determine if postoperative nausea and vomiting
      (PONV) or postoperative pain are associated with decreased breastfeeding success
      after cesarean delivery. Methods: This is a historical cohort study using the
      Stony Brook Elective Cesarean Delivery Database. Self-reported breastfeeding
      success at 4 weeks postoperative was analyzed for associations with postoperative
      antiemetic use and postoperative pain scores. Breastfeeding success was also
      analyzed for associations with patient factors and anesthetic medications.
      Results: Overall, 86% of patients (n = 81) who intended on breastfeeding reported
      breastfeeding success. Breastfeeding success was not associated with
      postoperative nausea or vomiting as measured by post anesthesia care unit
      antiemetic use (15% use in successful vs. 18% use in unsuccessful, p = 0.67) or
      48-h antiemetic use (28% use in successful group vs 36% use in unsuccessful
      group, p = 0.732). Pain visual analog scale scores at 6, 12 and 24 h
      postoperatively were not significantly different between patients with or without
      breastfeeding success. Breastfeeding success was associated with having had at
      least 1 previous child (86% vs 36%, p < 0.001). Patients with asthma were less
      likely to have breastfeeding success (45% vs 4%, p = 0.002). Conclusions: Efforts
      to improve PONV and pain after cesarean delivery may not be effective in
      improving breastfeeding success. To possibly improve breastfeeding rates,
      resources should be directed toward patients with no previous children and
      patients with asthma.

PMID- 29201360
TI  - Are physician assistant and patient airway assessments reliable compared to
      anesthesiologist assessments in detecting difficult airways in general surgical
      patients?
AB  - Background: Airway management remains one of the most important responsibilities
      of anesthesiologists. Prediction of difficult airway allows time for proper
      selection of equipment, technique, and personnel experienced in managing patients
      with difficult airway. Face to face preoperative anesthesia interviews are
      difficult to conduct as they necessitate patients traveling to the clinics, and,
      in practice, are usually conducted in the morning of the procedure by the
      anesthesiologist, when identification of predictors of difficult intubation may
      lead to schedule delays or case cancelations. We hypothesized that an airway
      assessment tool could be used by patients or physician assistants to accurately
      assess their airways. Methods: We administered an airway assessment tool, which
      had been constructed in consultation with a psychometrician and revised after non
      medical layperson feedback, to 215 patients presenting to the preoperative clinic
      for evaluation. Separately, patients had the airway exam performed by a physician
      assistant and an anesthesiologist. Agreement was compared using kappa. Results:
      We found good agreement between observers only on "can you put three fingers in
      your mouth?" (three-way kappa = .733, p < 0.001) and poor agreement on Mallampati
      classification (three-way kappa = .195, p < 0.001) and "Can you fit three fingers
      between your chin and your Adam's Apple?" (three-way kappa = .216, p < 0.001).
      The agreements for the other questions were mostly fair. Agreements between
      patients and anesthesiologists were similar to those between physician assistants
      and anesthesiologists. Conclusions: Neither the patients' self-assessments nor
      the physician assistants' assessments were adequate to substitute for the
      anesthesiologists' airway assessments.

PMID- 29201359
TI  - Rationale for and approach to preoperative opioid weaning: a preoperative
      optimization protocol.
AB  - The practice of chronic opioid prescription for chronic non-cancer pain has come
      under considerable scrutiny within the past several years as mounting evidence
      reveals a generally unfavorable risk to benefit ratio and the nation reels from
      the grim mortality statistics associated with the opioid epidemic. Patients
      struggling with chronic pain tend to use opioids and also seek out operative
      intervention for their complaints, which combination may be leading to increased
      postoperative "acute-on-chronic" pain and fueling worsened chronic pain and
      opioid dependence. Besides worsened postoperative pain, a growing body of
      literature, reviewed herein, indicates that preoperative opioid use is associated
      with significantly worsened surgical outcomes, and severely increased financial
      drain on an already severely overburdened healthcare budget. Conversely, there is
      evidence that preoperative opioid reduction may result in substantial
      improvements in outcome. In the era of accountable care, efforts such as the
      Enhanced Recovery After Surgery (ERAS) protocol have been introduced in an
      attempt to standardize and facilitate evidence-based perioperative interventions
      to optimize surgical outcomes. We propose that addressing preoperative opioid
      reduction as part of a targeted optimization approach for chronic pain patients
      seeking surgery is not only logical but mandatory given the stakes involved.
      Simple opioid reduction/abstinence however is not likely to occur in the absence
      of provision of viable and palatable alternatives to managing pain, which will
      require a strong focus upon reducing pain catastrophization and bolstering self
      efficacy and resilience. In response to a call from our surgical community toward
      that end, we have developed a simple and easy-to-implement outpatient
      preoperative optimization program focusing on gentle opioid weaning/elimination
      as well as a few other high-yield areas of intervention, requiring a minimum of
      resources.

PMID- 29201361
TI  - Quercetin prevents spinal motor neuron degeneration induced by chronic
      excitotoxic stimulus by a sirtuin 1-dependent mechanism.
AB  - Background: Excitotoxicity is a mechanism of foremost importance in the selective
      motor neuron degeneration characteristic of motor neuron disorders. Effective
      therapeutic strategies are an unmet need for these disorders. Polyphenols, such
      as quercetin and resveratrol, are plant-derived compounds that activate sirtuins
      (SIRTs) and have shown promising results in some models of neuronal death,
      although their effects have been scarcely tested in models of motor neuron
      degeneration. Methods: In this work we investigated the effects of quercetin and
      resveratrol in an in vivo model of excitotoxic motor neuron death induced by the
      chronic infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) into the rat spinal cord tissue. Quercetin and resveratrol were co-infused
      with AMPA and motor behavior and muscle strength were assessed daily for up to
      ten days. Then, animals were fixed and lumbar spinal cord tissue was analyzed by
      histological and immunocytological procedures. Results: We found that the chronic
      infusion of AMPA [1 mM] caused a progressive motor neuron degeneration,
      accompanied by astrogliosis and microgliosis, and motor deficits and paralysis of
      the rear limbs. Quercetin infusion ameliorated AMPA-induced paralysis, rescued
      motor neurons, and prevented both astrogliosis and microgliosis, and these
      protective effects were prevented by EX527, a very selective SIRT1 inhibitor. In
      contrast, neither resveratrol nor EX527 alone improved motor behavior deficits or
      reduced motor neuron degeneration, albeit both reduced gliosis. Conclusions:
      These results suggest that quercetin exerts its beneficial effects through a
      SIRT1-mediated mechanism, and thus SIRT1 plays an important role in excitotoxic
      neurodegeneration and therefore its pharmacological modulation might provide
      opportunities for therapy in motor neuron disorders.

PMID- 29201362
TI  - A generalized quantitative antibody homeostasis model: maintenance of global
      antibody equilibrium by effector functions.
AB  - The homeostasis of antibodies can be characterized as a balanced production,
      target-binding and receptor-mediated elimination regulated by an interaction
      network, which controls B-cell development and selection. Recently, we proposed a
      quantitative model to describe how the concentration and affinity of interacting
      partners generates a network. Here we argue that this physical, quantitative
      approach can be extended for the interpretation of effector functions of
      antibodies. We define global antibody equilibrium as the zone of molar
      equivalence of free antibody, free antigen and immune complex concentrations and
      of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]=KD. This zone
      corresponds to the biologically relevant KD range of reversible interactions. We
      show that thermodynamic and kinetic properties of antibody-antigen interactions
      correlate with immunological functions. The formation of stable, long-lived
      immune complexes correspond to a decrease of entropy and is a prerequisite for
      the generation of higher-order complexes. As the energy of formation of complexes
      increases, we observe a gradual shift from silent clearance to inflammatory
      reactions. These rules can also be applied to complement activation-related
      immune effector processes, linking the physicochemical principles of innate and
      adaptive humoral responses. Affinity of the receptors mediating effector
      functions shows a wide range of affinities, allowing the continuous sampling of
      antibody-bound antigen over the complete range of concentrations. The generation
      of multivalent, multicomponent complexes triggers effector functions by
      crosslinking these receptors on effector cells with increasing enzymatic
      degradation potential. Thus, antibody homeostasis is a thermodynamic system with
      complex network properties, nested into the host organism by proper
      immunoregulatory and effector pathways. Maintenance of global antibody
      equilibrium is achieved by innate qualitative signals modulating a quantitative
      adaptive immune system, which regulates molecular integrity of the host by tuning
      the degradation and recycling of molecules from silent removal to inflammatory
      elimination.

PMID- 29201363
TI  - Development and validation of makeup and sexualized clothing questionnaires.
AB  - Background: Body acceptance programs on college campuses indicated that
      collegiate women often report feeling pressure to dress in a sexualized manner,
      and use makeup to enhance beauty. Currently, no quantitative measures exist to
      assess attitudes and daily behaviors that may arise in response to perceived
      pressure to wear makeup or dress in a provocative manner. The goal of the current
      studies was to develop brief self-report questionnaires aimed at assessing makeup
      and sexualized clothing use and attitudes in young women. Methods: An exploratory
      factor analysis in a sample of 403 undergraduate women was used in Study 1 to
      create items to measure the pressure women feel to wear makeup and sexualized
      clothing. A confirmatory factor analysis (N = 153) was used in Study 2 to confirm
      the factor structure found in Study 1. An incremental validity analysis was also
      conducted in Study 2. Across both studies, participants completed online
      questionnaires. Results: In Study 1, items were developed for two questionnaires
      to assess perceived pressure to wear makeup and discomfort when not wearing
      makeup, and perceived pressure to wear sexualized clothing, and body image
      concerns with regards to sexualized clothing. The exploratory factor analyses
      revealed Unconfident and Unease scales for the Makeup Questionnaire (MUQ) and
      Body Dissatisfaction and Pressure scales for the Sexualized Clothing
      Questionnaire (SCQ). In Study 2, the confirmatory factor analyses confirmed the
      factor structure for the MUQ and SCQ. The incremental validity analysis revealed
      that these measures can be used to predict self-objectification and shape and
      weight concern in women. Conclusion: These studies provide preliminary support
      for the factor structure of two novel questionnaires aimed at assessing perceived
      pressure to wear makeup and sexualized clothing.

PMID- 29201364
TI  - The association between interpersonal problems and treatment outcome in patients
      with eating disorders.
AB  - Background: Interpersonal problems are thought to play an essential role in the
      development and maintenance of eating disorders. The aim of the current study was
      to investigate whether a specific interpersonal profile could be identified in a
      group of patients diagnosed with Bulimia Nervosa, Binge Eating Disorder, or
      Eating Disorders Not Otherwise Specified, and to explore if specific types of
      interpersonal problems were systematically related to treatment outcome in this
      group of patients. Methods: The participants were 159 patients who received
      systemic/narrative outpatient group psychotherapy. Interpersonal problems were
      measured at baseline, and eating disorder symptoms were measured pre- and post
      treatment. Data were analysed with the Structural Summary Method, a particular
      method for the analysis of the Inventory of Interpersonal Problems, and
      hierarchical regression analysis was conducted. Results: The patients
      demonstrated a generally Non-assertive and Friendly-submissive interpersonal
      style. No significant association between the overall level of interpersonal
      problems and treatment outcome was identified. However, the results showed a
      correlation between being cold and hostile and poor treatment outcome, while
      being domineering showed a trend approaching significance in predicting better
      treatment outcome. Conclusion: The results indicate that patients with eating
      disorders show a specific interpersonal profile, and suggest that particular
      types of interpersonal problems are associated with treatment outcome.

PMID- 29201365
TI  - Development of guidelines for giving community presentations about eating
      disorders: a Delphi study.
AB  - Background: Concerns exist around how to talk about eating disorders (EDs) due to
      evidence that suggests discussing ED symptoms and behaviours may cause or worsen
      symptoms in vulnerable people. Using expert consensus, we developed a set of
      guidelines for giving safe community presentations about EDs. Methods:
      Participants with professional ED expertise, and people with lived experience of
      an ED, were recruited for a Delphi study. N = 26 panel members rated 367
      statements for both a) inclusion in guidelines, and b) their potential to be
      helpful (increase knowledge, reduce stigma) or harmful (increase stigma,
      cause/worsen ED symptoms). After each round of the study, statements were
      classified as endorsed, re-rate, or not endorsed. Results: 208 statements were
      endorsed by the panel over three rounds. 13 statements were strongly endorsed in
      the first round, with both people with lived experience and professionals
      agreeing it is important for presentations to include information on etiology of
      EDs and to promote help-seeking. Several statements had a high level of
      disagreement between those with lived experience and professionals, including the
      idea that presentations should suggest dieting is likely to result in weight
      gain. Discussion: The experts were able to develop consensus on a wide range of
      issues. Panel members, particularly people with lived experience, were sensitive
      to aspects of presentations that may be harmful to an audience. The guidelines
      fill an important gap in the literature and provide guidance to those educating
      the public about EDs; they should, however, be further evaluated to test their
      efficacy.

PMID- 29201366
TI  - Survey on the availability, price and affordability of selected essential
      medicines for non-communicable diseases in community pharmacies of Kathmandu
      valley.
AB  - Background: The access to essential medicines for non-communicable disease
      treatment is unacceptably low worldwide. The fundamental right to health cannot
      be fulfilled without equitable access to essential medicines. Methodology: A
      cross-sectional study was carried out in 94 community pharmacies of Kathmandu
      valley. Non-probability quota sampling method was adopted for the purpose.
      Village Development Committees with more than 5000 populations were included in
      the study. The availability of the selected essential medicines, their price and
      producer identity were observed. Data entry and analysis were carried out in
      Microsoft Excel and Statistical package for social science. Result: The
      availability of the essential medicines was not 100% in Kathmandu valley. High
      competition and high price variation were seen in metformin 500 mg (254.6%) and
      atorvastatin 10 mg (327.6%). The study showed that maximum (54.7%) brands were
      manufactured in Nepal. Furthermore, atorvastatin 10 mg (0.6 day wage) was found
      to be quite expensive, and glibenclamide 5 mg (0.1 day wage) was the cheapest one
      for diabetes mellitus treatment for 1 month of treatment period compared to daily
      wages of other essential medicines. Conclusion: The availability of the selected
      essential medicines was found to be ununiform and insufficient in the entire
      region. High competition was observed in the products with high price variation,
      and the access to cost-effective brand was poor. Furthermore, it was found that
      government salary is affordable to treat non-communicable disease with the help
      of the essential medicines.

PMID- 29201367
TI  - Services aimed at achieving desirable clinical outcomes in patients with chronic
      kidney disease and diabetes mellitus: A narrative review.
AB  - There is a large number of patients with chronic kidney disease (CKD), diabetes
      mellitus (DM), and hypertension (HT) but whether the targets on blood pressure
      (BP) control in patients with DM and/or CKD are met is not clear. This narrative
      review therefore investigated evidence on services aimed at achieving desirable
      clinical results in patients with CKD and DM, and HT in Australia. Literature
      pertaining to pathology diagnosis and management of these patients as well as the
      complexities in management were considered. This involved evidence from PubMed
      listed articles published between 1993 and 2016 including original research
      studies, focusing on randomised controlled trials and prospective studies where
      possible, systematic and other review articles, meta- analyses, expert consensus
      documents and specialist society guidelines, such as those from the National
      Heart Foundation of Australia, American Diabetes Association, the Department of
      Health, The Royal College of Pathologists of Australasia, and The Australasian
      College of Emergency Medicine. Based on the literature reviewed, it is yet
      unknown as to how effective programs, such as diabetes inpatient services,
      endocrine out-patient services, and cardiac rehabilitation services, are at
      achieving guideline recommendations. It is also not clear how or whether
      clinicians are encumbered by complexities in their efforts of adhering to DM, HT,
      and glucose control recommendations, and the potential reasons for clinical
      inertia. Future studies are needed to ascertain the extent to which required BP
      and glucose control in patients is achieved, and whether clinical inertia is a
      barrier.

PMID- 29201368
TI  - Medication use and falls: Applying Beers criteria to medication review in
      Parkinson's disease.
AB  - Objectives: Our goal was to assess the association between potentially
      inappropriate medication use and risk of falls in the Parkinson's disease
      population. Methods: This was a retrospective cohort study conducted at an
      outpatient Parkinson's Disease Treatment Center. Individuals 65 years of age or
      older, diagnosed with Parkinson's disease who attended at least three visits in
      2015 for physical, occupational therapy, or physician's visits were included in
      the study. Electronic medical records were utilized to perform chart reviews, and
      medications were analyzed to identify prescription medications, combination
      preparations, over-the-counter medications, and dietary supplements. The goal of
      this study was to test the following hypothesis: elderly individuals with
      Parkinson's disease who take multiple potentially inappropriate medications are
      more likely to experience a fall compared to elderly individuals with Parkinson's
      disease who do not take multiple potentially inappropriate medications. Results:
      A higher mean number of prescription medications were associated with falls in
      elderly Parkinson's disease patients (6.53 vs 5.21, p < 0.01). Polypharmacy
      (taking five or more prescription and nonprescription medications) was not
      significantly associated with falls. Patients taking potentially inappropriate
      medications specifically contraindicated for those with a history of falls and
      fractures were more likely to report falls (p < 0.04). Analysis of the specific
      therapeutic medication categories demonstrated no significant differences between
      those who did and did not report falls. Conclusion: A future prospective study at
      Parkinson's disease center should include an electronic medical record-based
      intervention to reduce the total number of medications, as well as to minimize
      the use of high-risk medications.

PMID- 29201369
TI  - X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological
      manifestations.
AB  - Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism
      occurring predominantly in males with onset in early 30s. Here, we report a 34
      year-old male with first signs of disease in early 20s manifesting as a pure
      psychiatric disorder. Prior to onset of neurological symptoms, this patient
      demonstrated a schizophrenia and bipolar-like presentation. The disease
      progressed over the next 10-13 years and his memory and motor problems became
      evident around the age of 33 years. Subsequently, diagnostic testing showed the
      typical magnetic resonance imaging and lab findings for adult-onset
      adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which
      may present as a pure psychiatric disturbance in early adulthood and briefly
      discusses the prolonged time between the onset of psychiatric symptoms and the
      onset of neurological disease.

PMID- 29201370
TI  - Salvage of mangled upper extremity using the Masquelet technique in a child: A
      case report.
AB  - Aim: To report our experience with the Masquelet concept in a pediatric upper
      extremity following an open injury to the elbow. Methods: A case report and
      literature review. Results: An 11-year-old boy was transferred to our institution
      after a motor vehicle collision. There was a primary loss of the ulnohumeral
      articulation and the surrounding soft tissues as well as the ulnar nerve.
      Reconstruction used the Masquelet-induced membrane technique and a soft tissue
      flap. At the 30-month follow-up, the extremity was pain free and functional.
      Conclusion: This case highlights the value of the Masquelet technique in
      pediatric extremity injuries, where there is a loss of a major articular segment,
      as well as significant soft tissue compromise.

PMID- 29201371
TI  - Giant thrombosed saphenofemoral junction aneurysm: A case report.
AB  - Introduction: Although saphenofemoral junction aneurysms are not so rare, only
      scarce of the published cases reported thrombosis of the aneurysmal sac and
      saphenous trunk. Presentation of case: A 65-year-old male with varicose disease,
      developed acute ascending superficial vein thrombosis of the left greater
      saphenous vein, involving the 6-cm saphenofemoral junction aneurysm. The patient
      underwent common femoral vein thrombectomy, aneurysm removal, and greater
      saphenous vein excision with uneventful postoperative course. Conclusion:
      Thrombosed giant saphenofemoral junction aneurysms require emergent surgical
      intervention aimed at preventing potential progression to deep vein thrombosis
      and pulmonary embolism.

PMID- 29201372
TI  - The importance of pheochromocytoma case detection in patients with
      neurofibromatosis type 1: A case report and review of literature.
AB  - Neurofibromatosis type 1 is a complex, multi-system genetic disorder that is
      associated with an increased prevalence of pheochromocytoma and paraganglioma
      compared to the general population, 1.0%-5.7% versus 0.2%-0.6%, respectively. A
      delay in pheochromocytoma and paraganglioma diagnosis or undiagnosed
      pheochromocytoma and paraganglioma, as seen in normotensive and asymptomatic
      patients, may portend a significant morbidity and mortality risk due to excess
      catecholamine secretion. Currently, there are no generally accepted guidelines of
      screening for pheochromocytoma and paragangliomas in asymptomatic individuals of
      this population with approaches and practices varying considerably between
      physicians. Emerging data suggest benefit in routine pheochromocytoma and
      paraganglioma screening of all individuals with neurofibromatosis type 1. Herein,
      we present a case to highlight how routine case detection screening would have
      identified pheochromocytoma earlier in an active duty military member.

PMID- 29201373
TI  - Free anterolateral thigh full-thickness skin flap with vascularized lateral
      femoral cutaneous nerve for the reconstruction of facial nerve and external
      auditory canal after the resection of facial nerve schwannoma.
AB  - The complex reconstruction of nerves and soft tissue in the head and neck region
      is still challenging, especially in cases requiring external auditory canal
      reconstruction with facial nerve reconstruction. We report a case of left facial
      schwannoma extending into the external auditory canal beyond the tympanic
      membrane with facial paralysis in which the reconstruction of both the facial
      nerve and external auditory canal was successfully performed using an
      anterolateral thigh flap as a super-thin full-thickness skin flap, including
      vascularized lateral femoral cutaneous nerve. Resection of 20 mm * 46 mm facial
      schwannoma, including the skin of the external auditory canal, tympanic membrane,
      incus and malleus, was performed. The 8-cm nerve gap was repaired using a
      vascularized lateral femoral cutaneous nerve included in the anterolateral thigh
      flap. An 8 cm * 2 cm super-thin, free anterolateral thigh flap was then rolled up
      as a sac (diameter of 2 cm, height of 2 cm) and inset to the external auditory
      canal defect. The postoperative course was uneventful, and the flap survived
      completely. One year and nine months after the surgery, the patient's facial
      movement has improved to the pre-surgery level.

PMID- 29201375
TI  - Children with lymphadenitis associated with Bacillus Calmette-Guerin (BCG)
      vaccination do not experience more infections when compared with BCG-vaccinated
      children without lymphadenitis: a three years paired-cohort in Mexico.
AB  - Objectives: Vaccination against tuberculosis with live-attenuated Bacillus
      Calmette-Guerin (BCG) is widely used even though its effectiveness is
      controversial. BCG-lymphadenitis (BCG-LA) is its most common complication. Some
      studies have proposed that BCG-LA can be associated with primary
      immunodeficiencies (PIs). This study's aim is to see whether patients who
      developed BCG-LA (named as 'LA') developed more infections than BCG-vaccinated
      children without BCG-LA (named as 'NON-LA'). Methods: From January 2009 to April
      2014, 31 LA children were seen at the outpatient clinic of the General Hospital
      of Tijuana, Mexico. Among them, 22 (70.97%), 5 (16.13%) and 4 (12.9%) had
      axillary, supraclavicular, or both BCG-LA, respectively. No treatment was given
      and complications were not seen. Per LA subject, a NON-LA not >1 month of age
      difference and same gender was paired and followed for 3 years to look for
      ambulatory infections (AINFs), acute otitis media (AOM) and hospitalizations.
      Surveillance per patient was performed by phone monthly, and they were seen at
      the clinic every 4 months. All patients were HIV-negative and had no family
      history of PI. Statistical analyses used were relative risk (RR) with confidence
      intervals (CI), t test for independent variables and z test. Results: In total 62
      subjects were enrolled: 31 LA paired with 31 NON-LA. Between them, there were no
      differences in age, day care attendance and breastfeeding. There were no
      differences in the total number of AINF per patient (LA: 18.61 avg. +/- 5.03 SD
      versus NON-LA: 18.19 avg. +/- 4.17 SD, RR = 1.06, 95% CI = 0.33-0.66), AOM total
      episodes (LA: 30 versus NON-LA: 26, RR = 0.87, 95% CI = 0.31-0.68) and
      hospitalizations (LA: 5 versus NON-LA: 4, RR = 1, 95% CI = 0.25-0.74).
      Conclusions: This cohort strongly suggests that BCG-LA in healthy children is not
      associated with more episodes of AINF and hospitalizations, when paired and
      compared with children BCG-vaccinated without BCG-LA.

PMID- 29201374
TI  - Liposomal adjuvant development for leishmaniasis vaccines.
AB  - Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to
      fatality. Since long-lasting protection is induced upon recovery from cutaneous
      leishmaniasis, development of an effective vaccine is promising. However, there
      is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis
      vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the
      use of particulate adjuvants such as liposomes for effective delivery to the
      antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis
      vaccine efficacy. The extraordinary versatility of liposomes because of their
      unique amphiphilic and biphasic nature allows for using antigens or
      immunostimulators within the core, on the surface or within the bilayer, and
      modulates both the magnitude and the T-helper bias of the immune response. In
      this review article, we attempt to summarize the role of liposomal adjuvants in
      the development of Leishmania vaccines and describe the main physicochemical
      properties of liposomes like phospholipid composition, surface charge, and
      particle size during formulation design. We also suggest potentially useful
      formulation strategies in order for future experiments to have a chance to
      succeed as liposomal vaccines against leishmaniasis.

PMID- 29201376
TI  - Quantifying animal movement for caching foragers: the path identification index
      (PII) and cougars, Puma concolor.
AB  - Background: Many studies of animal movement have focused on directed versus area
      restricted movement, which rely on correlations between step-length and turn
      angles and on stationarity through time to define behavioral states. Although
      these approaches might apply well to grazing in patchy landscapes, species that
      either feed for short periods on large, concentrated food sources or cache food
      exhibit movements that are difficult to model using the traditional metrics of
      turn-angle and step-length alone. Results: We used GPS telemetry collected from a
      prey-caching predator, the cougar (Puma concolor, Linnaeus), to test whether
      combining metrics of site recursion, spatiotemporal clustering, speed, and
      turning into an index of movement using partial sums, improves the ability to
      identify caching behavior. The index was used to identify changes in movement
      characteristics over time and segment paths into behavioral classes. The
      identification of behaviors from the Path Identification Index (PII) was
      evaluated using field investigations of cougar activities at GPS locations. We
      tested for statistical stationarity across behaviors for use of topographic view
      sheds. Changes in the frequency and duration of PII were useful for identifying
      seasonal activities such as migration, gestation, and denning. The comparison of
      field investigations of cougar activities to behavioral PII classes resulted in
      an overall classification accuracy of 81%. Conclusions: Changes in behaviors were
      reflected in cougars' use of topographic view-sheds, resulting in statistical
      nonstationarity over time, and revealed important aspects of hunting behavior.
      Incorporating metrics of site recursion and spatiotemporal clustering revealed
      the temporal structure in movements of a caching forager. The movement index PII,
      shows promise for identifying behaviors in species that frequently return to
      specific locations such as food caches, watering holes, or dens, and highlights
      the potential role memory and cognitive abilities play in determining animal
      movements.

PMID- 29201377
TI  - Use of wearable devices for post-discharge monitoring of ICU patients: a
      feasibility study.
AB  - Background: Wearable devices generate signals detecting activity, sleep, and
      heart rate, all of which could enable detailed and near-continuous
      characterization of recovery following critical illness. Methods: To determine
      the feasibility of using a wrist-worn personal fitness tracker among patients
      recovering from critical illness, we conducted a prospective observational study
      of a convenience sample of 50 stable ICU patients. We assessed device
      wearability, the extent of data capture, sensitivity and specificity for
      detecting heart rate excursions, and correlations with questionnaire-derived
      sleep quality measures. Results: Wearable devices were worn over a 24-h period,
      with excellent capture of data. While specificity for the detection of
      tachycardia was high (98.8%), sensitivity was low to moderate (69.5%). There was
      a moderate correlation between wearable-derived sleep duration and questionnaire
      derived sleep quality (r = 0.33, P = 0.03). Devices were well-tolerated and
      demonstrated no degradation in quality of data acquisition over time.
      Conclusions: We found that wearable devices could be worn by patients recovering
      from critical illness and could generate useful data for the majority of patients
      with little adverse effect. Further development and study are needed to better
      define and enhance the role of wearables in the monitoring of post-ICU recovery.
      Trial registration: Clinicaltrials.gov, NCT02527408.

PMID- 29201378
TI  - Time to re-think the use of dobutamine in sepsis.
AB  - Dobutamine is commonly used worldwide and included in the protocol for early goal
      directed therapy (EGDT). Since the use of dobutamine in EGDT was reported, it has
      been considered to be an important component, especially in the treatment of
      septic patients with myocardial dysfunction. However, it is questionable whether
      dobutamine improves the mortality of sepsis and septic shock. In three recent
      randomized controlled trials (ProCESS, ProMISe, and ARISE trials), the frequency
      of dobutamine use was significantly higher in the EGDT group than in the standard
      care group, but there were no significant differences in the mortality between
      the groups. These results suggested that dobutamine use may have been
      overemphasized despite its insignificant effect on the mortality in septic
      patients. Further, a propensity score analysis revealed that dobutamine use was
      associated with higher mortality in patients with septic shock. Although
      dobutamine leads to an increase in cardiac index, myocardial oxygen demand also
      increases, thus increasing the risk of myocardial ischemia and tachyarrhythmia.
      It is well known that the mortality in sepsis complicated with atrial
      fibrillation (AFib) is worse than that in sepsis without AFib. A propensity score
      matched analysis reported that beta-blockers were associated with better survival
      in patients with sepsis complicated with AFib. Further, a randomized controlled
      trial reported that a short-acting beta-blocker improved the survival in patients
      with septic shock. These studies also indicated the risk of beta-stimulation
      during sepsis. Notably, improvements in surrogate markers, such as CI, do not
      always indicate improvements in patient-centered outcomes, such as mortality.
      Conversely, some evidence indicates the worsening of patient-centered outcomes
      despite improvements in surrogate markers. Thus, available evidence suggests that
      the benefits of dobutamine in patients with sepsis are unclear, but its use might
      be harmful rather than beneficial, considering the beneficial effects of beta
      blockers in sepsis that have been reported in recent clinical studies. From this
      perspective, we will soon have to rethink regarding dobutamine use in patients
      with sepsis.

PMID- 29201379
TI  - Knowledge, attitude and practice of students towards blood donation in Arsi
      university and Adama science and technology university: a comparative cross
      sectional study.
AB  - Background: Blood can save millions of lives. Even though people do not donate
      blood regularly, there is a constant effort to balance the supply and demand of
      blood. The aim of this study was, therefore, to determine the knowledge, attitude
      and practice of blood donation between university students. Methods: The
      comparative cross sectional study design was used in Adama Science and Technology
      University and Arsi University from April 11-May 2, 2016.360 students were
      selected using stratified sampling. Frequencies and proportions were computed.
      Chi-Square and logistic regressions were carried out and associations were
      considered significant at p<0.05. Result: The study revealed that there was a
      significant knowledge difference (chi2 = 152.779, p<0.001) and Attitude
      difference (chi2 = 4.142, p = 0.042) between Health Science students of Arsi
      University and Non-Health Science students of Adama Science and Technology
      University. The gender of the students (AOR = 3.150, 95% CI: 1.313, 7.554) was a
      significant predictor of the level of knowledge of Health Science students. The
      ethnicity of students (AOR = 2.085, 95% CI: 1.025, 4.243) was a significant
      predictor of the level of an attitude of Health Science students and gender of
      students (AOR = 0.343, 95% CI: 0.151, 0.779) was a significant predictor of the
      level of an attitude of Health Science students. Concerning Non-Health Science
      students, religion (AOR = 10.173, 95% CI: 1.191, 86.905) and original residence
      (AOR = 0.289, 95% CI: 0.094, 0.891) were a significant predictor of the level of
      knowledge of Non-Health Science students. Gender (AOR = 0.389, 95% CI: 0.152,
      0.992) and Year of study (AOR = 0.389(0.164, 0.922) were significant predictor of
      level of attitude of Non-Health Science students. Year of study (AOR = 5.159, 95%
      CI: 1.611, 16.525) was a significant predictor of level of practice of Health
      Science students. Conclusion: Significant knowledge difference and attitude
      difference were observed between students from Arsi University and Adama Science
      and Technology University.

PMID- 29201380
TI  - First case of bacteraemia due to Acinetobacter schindleri harbouring blaNDM-1 in
      an immunocompromised patient.
AB  - Clinically significant NDM-1-producing Acinetobacter schindleri has not yet been
      described in the literature. We report the first case of bacteraemia due to an A.
      schindleri strain harbouring blaNDM-1 recovered from an immunocompromised
      patient. Our report reinforces the fact that NDM-1 can easily be acquired by
      Acinetobacter species.

PMID- 29201381
TI  - Culture-independent genome sequencing of Coxiella burnetii from a native heart
      valve of a Tunisian patient with severe infective endocarditis.
AB  - We report draft genome of a Coxiella burnetii strain sequenced from the native
      valve of a patient presenting with severe endocarditis in Tunisia. The genome
      could be sequenced without a cellular or axenic culture step. The MST5 strain was
      demonstrated to be closely related to the published reference genome of C.
      burnetii CbuK_Q154.

PMID- 29201382
TI  - Optimization of interpolation method for nitrate pollution in groundwater and
      assessing vulnerability with IPNOA and IPNOC method in Qazvin plain.
AB  - Background: The presence of nitrate is one of the factors limiting the quality of
      groundwater resources, particularly in arid and semi-arid climates. Therefore,
      the knowledge about the distribution of nitrate in groundwater and its source has
      an effective role in protecting health. The study aimed to optimize an
      interpolation method to predict the nitrate concentration and assessment of
      aquifer vulnerability in Qazvin plain. Methods: One hundred sixty-two deep wells
      in Qazvin plain aquifer were randomly selected and nitrate concentration was
      analyzed in four different lands including agricultural, residential, steppe and
      mixed-use areas. Interpolation was done by IDW, Spline, Kriging and National
      neighbor methods using ArcGIS software. To select the best interpolation method,
      errors of predicted values were determined by Mean Relative Error (RME) and Root
      Mean Square Error (RMSE). For analysis of potential vulnerability of aquifer to
      nitrate pollution due to agricultural activity and sewage leaks, hazard factors
      and control factors were used for identification of hazard indexes (HI) using
      IPNOA and IPNOC model. Results: The results showed that in 8.82% and 18.52% of
      samples in agricultural and residential areas, the detected nitrate was above the
      acceptable level at 50 mg/L. National neighbor method with the lowest RME and
      Spline method with the lowest RMSE were provided the most accurate estimates of
      nitrates in the aquifer. The highest hazard was obtained in agricultural areas
      (HI = 6.11). Also, the most influential parameters on aquifer vulnerability were
      mineral fertilizer (HFf = 3), organic fertilizers (HFm = 3), irrigation systems
      (CFi = 1.04) and tillage patterns (CFap = 1.04). Conclusions: According to the
      results, National neighbor with the lowest RME was preferable than the other
      spatial interpolation methods for prediction of nitrate concentration in the
      aquifer. This method provided similar spatial distribution maps of nitrate in
      groundwater and that was an efficient method for assessing water quality. Hazard
      index as a result of agricultural activities (IPNOA) was ranged from "very low"
      to "low" which was in accordance with detected and predicted nitrate
      concentration in the aquifer. In addition he hazard of nitrate contamination from
      household (IPNOC) was in very low (class 2).

PMID- 29201383
TI  - An autosomal recessive mutation in SCL24A4 causing enamel hypoplasia in Samoyed
      and its relationship to breed-wide genetic diversity.
AB  - Background: Pure breeding of dogs has led to over 700 heritable disorders, of
      which almost 300 are Mendelian in nature. Seventy percent of the characterized
      mutations have an autosomal recessive mode of inheritance, indicative of positive
      selection during bouts of inbreeding primarily for new desired conformational
      traits. Samoyed suffer from several common complex genetic disorders, but up to
      this time only two X-linked and one autosomal dominant disorder have been
      identified. Previous studies based on pedigrees and SNP arrays have concluded
      that Samoyed breeders have done a good job in maintaining genetic diversity and
      avoiding excessive inbreeding. This may explain why autosomal recessive disorders
      have not occurred to the extent observed in many other breeds. However, an enamel
      hypoplasia analogous to a form of autosomal recessive amelogenesis imperfecta
      (ARAI) in humans has been recently characterized in Samoyed, although the
      causative mutation appears to have existed for three or more decades. The rise of
      such a mutation indicates that bouts of inbreeding for desired conformational
      traits are still occurring despite an old and well-defined breed standard.
      Therefore, the present study has two objectives: 1) measure genetic diversity in
      the breed using DNA and short tandem repeats (STR), and 2) identify the exact
      mutation responsible for enamel hypoplasia in the breed, possible explanations
      for its recent spread, and the effect of eliminating the mutation on existing
      genetic diversity. Results: The recent discovery of an autosomal recessive
      amelogenesis imperfecta (ARAI) in Samoyed provides an opportunity to study the
      mutation as well as genetic factors that favored its occurrence and subsequent
      spread. The first step in the study was to use 33 short tandem repeat (STR) loci
      on 25/38 autosomes and seven STRs across the dog leukocyte antigen (DLA) class I
      and II regions on CFA12 to determine the DNA-based genetic profile of 182
      individuals from North America, Europe and Australia. Samoyed from the three
      continents constituted a single breed with only slight genetic differences. Breed
      wide genetic diversity was low, most likely from a small founder population and
      subsequent artificial genetic bottlenecks. Two alleles at each autosome locus
      occurred in 70-95% of the dogs and 54% of alleles were homozygous. The number of
      DLA class I and II haplotypes was also low and three class I and two class II
      haplotypes occurred in 80-90% of individuals. Therefore, most Samoyed belong to
      two lines, with most dogs possessing a minority of existing genetic diversity and
      a minority of dogs containing a majority of diversity. Although contemporary
      Samoyed lack genetic diversity, the bulk of parents are as unrelated as possible
      with smaller subpopulations either more inbred or outbred than the total
      population. A familial disorder manifested by hypocalcification of enamel has
      been recently identified. A genome wide association study (GWAS) on seven
      affected and five unrelated healthy dogs pointed to a region of extended
      homozygosity on Canis familiaris autosome 8 (CFA8). The region contained a gene
      in the solute carrier 24 family (SCL24A4) that encodes a protein involved in
      potassium dependent sodium/calcium exchange and transport. Mutations in this gene
      were recently found to cause a similar type of enamel hypoplasia in people.
      Sequencing of this candidate gene revealed a 21 bp duplication in exon 17. A test
      for the duplication was in concordance with the disease phenotype. The exact
      incidence of affected dogs is unknown, but 12% of the 168 healthy dogs tested
      were heterozygous for the mutation. This population was biased toward close
      relatives, so a liberal estimate of the incidence of affected dogs in the breed
      would be around 3.6/1000. Theoretical calculations based on the comparison of the
      whole population with a population devoid of carriers indicated that eliminating
      the trait would not affect existing genetic diversity at this time. Conclusions:
      The contemporary Samoyed, like many other breeds, has retained only a small
      portion of the genetic diversity that exists among all dogs. This limited genetic
      diversity along with positive genetic selection for desirable traits has led to
      at least three simple non-recessive genetic disorders and a low incidence of
      complex genetic traits such as autoimmune disease and hip dysplasia. Unlike many
      other pure breeds, the Samoyed has been spared the spate of deleterious autosomal
      recessive traits that have plagued many other pure breeds. However, ARAI due to a
      mutation in the SCL24A4 gene has apparently existed in the breed for several
      decades but is being increasingly diagnosed. The increase in diseased dogs is
      most likely due to a period of intensified positive selection for some desired
      conformational trait. A genetic test has been developed for identifying the
      mutation carriers which will enable the breeders to eliminate enamel hypoplasia
      in Samoyed by selective breeding and it appears that this mutation can be
      eliminated now without loss of genetic diversity.

PMID- 29201384
TI  - Rottweilers under primary veterinary care in the UK: demography, mortality and
      disorders.
AB  - Background: Rottweilers are reportedly predisposed to many disorders but accurate
      prevalence information relating to the general population are lacking. This study
      aimed to describe demography, mortality and commonly recorded diseases in
      Rottweilers under UK veterinary care. Clinical health records within the
      VetCompass Programme were explored for disorders recorded during 2013. Results:
      Rottweilers comprised 5321 (1.17%) of 455,557 dogs attending 304 clinics. Annual
      proportional birth rates dropped from 1.75% in 2006 to 1.07% in 2013. Median
      adult bodyweight overall was 44.9 kg (IQR 39.55-51.00, range 20.00-88.80). Median
      male adult bodyweight (48.5 kg, interquartile range [IQR] 43.0-54.0, range 20.0
      88.8) was heavier than female (41.5 kg, IQR 37.0-46.4, range 21.1-73.5) (P <
      0.001). Median longevity overall was 9.0 years (IQR 7.2-10.5, range 0.0-17.0).
      Median female longevity (9.5 years, IQR 7.8-11.0) was greater than male (8.7
      years, IQR 6.8-10.1) (P = 0.002). The most common causes of death were neoplasia
      (33.0%), inability to stand (16.0%) and mass-associated disorder (7.1%).At least
      one disorder was recorded for 60.31% of Rottweilers. The most prevalent specific
      disorders recorded were aggression (7.46%, 95% CI 6.40-8.64), overweight/obesity
      (7.06%, 95% CI: 6.02-8.21), otitis externa (6.14%, 95% CI: 5.18-7.23) and
      degenerative joint disease (4.69%, 95% CI: 3.84-5.66). Male Rottweilers had
      higher prevalence than females for aggression (9.36% versus 5.47%, P = 0.001) and
      pyotraumatic dermatitis (4.05% versus 1.76%, P = 0.001). Aggression was more
      prevalent in neutered than entire females (7.5% versus 3.1%, P = 0.003) but did
      not differ between neutered and entire males (9.6% versus 9.0%, P = 0.773). The
      most frequent disorder groups were musculoskeletal (12.01%, 95% CI: 10.69-13.45),
      dermatological (10.96%, 95% CI: 9.69-12.35), gastro-intestinal (195, 8.87%, 95%
      CI: 7.72-10.14), undesirable behaviour (7.96%, 95% CI: 6.87-9.18) and neoplasia
      (7.96%, 95% CI: 6.87-9.18). Conclusions: The current study assists prioritisation
      of health issues within Rottweilers. Rottweilers are relatively short-lived and
      neoplasia is a common cause of death. The most common disorders were aggression,
      overweight/obesity, otitis externa and degenerative joint disease. Males were
      significantly heavier, shorter-lived and predisposed to aggression than females.
      These results can alert prospective owners to potential health issues and
      optimise sex selection decision-making.

PMID- 29201385
TI  - Identifying the hidden burden of allergic rhinitis (AR) in community pharmacy: a
      global phenomenon.
AB  - Background: Patients with allergic rhinitis often trivialise their condition,
      self-manage inappropriately, and would benefit from health care intervention. The
      primary point of health care contact for these self-managing allergic rhinitis
      patients is the community pharmacy. With the majority of allergic rhinitis
      treatments being available for purchase over the counter, without health care
      professional contact, we know little about how the patients self-manage. This
      study aims to identify the burden of allergic rhinitis in the community pharmacy
      and to identify key opportunity for intervention. Methods: Pharmacy customers,
      who purchased nasal treatment in a community pharmacy, were approached with a
      research-administered questionnaire that collected data on medical history,
      symptoms and products purchased for the treatment of nasal symptoms. Results: Of
      the 296 participants, 69.9% self-managed with over-the-counter medications; with
      68% experiencing allergic rhinitis symptoms and only 44.3% of this subgroup had a
      doctor's diagnosis. Nasal congestion (73.6%) was most commonly experienced and
      oral antihistamines were most commonly purchased (44.3%), indicating a pattern of
      suboptimal management. A third of participants (36.5%) experienced moderate
      severe symptoms, persistently, which impacted on their daily living. Medication
      selection was mainly based on pharmacy customers' perceptions of medication
      effectiveness (47.6%). Conclusion: A majority of participants that self-selected
      over-the-counter medications have symptoms consistent with allergic rhinitis,
      with almost half not having received a diagnosis. Medication purchasing patterns
      suggest that sub-optimal therapeutic decisions made by participants, even when
      they are experiencing significant symptoms. This study uncovers the hidden burden
      of allergic rhinitis in the community pharmacy and a missed opportunity to
      intervene and refer if necessary. Patients need to be guided through appropriate
      treatment as this study showed that many should be referred to a medical
      practitioner.

PMID- 29201386
TI  - Meta-research metrics matter: letter regarding article "indirect tolerability
      comparison of Deutetrabenazine and Tetrabenazine for Huntington disease".
AB  - Here we discuss the report by Claassen and colleagues describing an indirect
      treatment comparison between tetrabenazine and deutetrabenazine for chorea in
      Huntington's disease using individual patient data. We note the potential for
      discrepancies in apparently statistically significant findings, due to the rank
      reversal phenomenon. We provide some cautionary observations and suggestions
      concerning the limitations of indirect comparisons and the low likelihood that
      good quality evidence will become available to guide clinical decision comparing
      these two agents.

PMID- 29201387
TI  - A half century of electronic fetal monitoring and bioethics: silence speaks
      louder than words.
AB  - Bioethics abolished the prevailing Hippocratic tenet instructing physicians to
      make treatment decisions, replacing it with autonomy through informed consent.
      Informed consent allows the patient to choose treatment after options are
      explained by the physician. The appearance of bioethics in 1970 coincided with
      the introduction of electronic fetal monitoring (EFM), which evolved to become
      the fetal surveillance modality of choice for virtually all women in labor.
      Autonomy rapidly pervaded all medical procedures, but there was a clear exemption
      for EFM. Even today, EFM remains immune to the doctrine of informed consent
      despite continually mounting evidence which proves the procedure is nothing more
      than myth, illusion and junk science that subjects mothers and babies alike to
      increased risks of morbidity and mortality. And ethicists have remained utterly
      silent through a half century of EFM misuse. Our article explores this egregious
      ethical failure by reviewing EFM's lack of clinical efficacy, discussing the EFM
      related harm to mothers and babies, and focusing on the reasons that this
      obstetrical procedure eluded the revolutionary change from the Hippocratic
      tradition to autonomy through informed consent.

PMID- 29201389
TI  - The feasibility of assessing swallowing physiology following prolonged intubation
      after cardiovascular surgery.
AB  - Background: Dysphagia following prolonged intubation after cardiovascular (CV)
      surgery is common occurring in 67% of patients; however, this population's
      swallowing physiology has never been prospectively evaluated using standardized
      methods. Hence, prior to conducting a larger study, our primary objective was to
      determine the feasibility of assessing swallowing physiology using
      instrumentation and validated interpretation methods in cardiovascular surgical
      patients following prolonged intubation. Method: From July to October 2011, we
      approached adults undergoing CV surgery at our institution who were intubated >
      48 h. Those with a tracheostomy were excluded. Videofluoroscopic swallowing study
      (VFS) and nasendoscopy were completed within 48 h after extubation. Feasibility
      measurements included recruitment rate, patient participation, task completion
      durations, and the inter-rater reliability of VFS measures using the intraclass
      correlation coefficient (ICC). VFSs were interpreted using perceptual rating
      tools (Modified Barium Swallow Measurement Tool for Swallow ImpairmentTM(c) and
      Penetration Aspiration Scale) and objective displacement measurements (hyoid
      displacement and pharyngeal constriction ratio). Results: Of the 39 patients
      intubated > 48 h, 16 met inclusion criteria with three enrolled and completing
      the VFS. All refused nasendoscopy. Across all VFSs, rating completion time ranged
      from 14.6 to 51.7 min per patient with ICCs for VFS scales ranging from 0.25 (95%
      CI - 0.10 to 0.59) to 0.99 (95% CI 0.98 to 0.99). Conclusions: This study design
      was not feasible as recruitment was slow, few patients participated, and no
      patient agreed to all procedures. We discuss necessary methodological changes and
      lessons learned that would generalize to future research.

PMID- 29201388
TI  - Evaluating the feasibility of conducting a trial using a patient decision aid in
      implantable cardioverter defibrillator candidates: a randomized controlled
      feasibility trial.
AB  - Background: Patient decision aids (PtDA) support quality decision-making. The aim
      of this research was to evaluate the feasibility of conducting a randomized
      controlled trial delivering an implantable cardioverter defibrillator (ICD)
      specific PtDA to new ICD candidates and examining preliminary estimates of
      differences in outcomes. Methods: Prior to recruitment, ICD candidacy was
      determined. Consented patients were randomized to (1) usual care or (2) PtDA
      intervention. Feasibility outcomes included referral and recruitment rates,
      successful PtDA delivery, and completion of measures. The PtDA intervention was
      administered prior to specialist consultation and baseline demographics, and
      measures of decision quality including decisional conflict (DCS), SURE test (Sure
      of myself, Understand information, Risk-benefit ratio, Encouragement), patient's
      ICD specific values, ICD knowledge, and health-related quality of life were
      recorded. Post-consultation, participant's DCS was repeated and decisions to
      proceed, decline, or defer ICD implantation were collected. Feasibility data was
      determined using descriptive statistics (continuous and categorical). Preliminary
      estimates of differences in outcomes were assessed using mean differences.
      Concordance between values and decision choice was assessed using logistic
      regression of the intervention group. Results: We identified 135 eligible
      patients. Eighty-two consented to the trial randomizing patients to usual care (n
      = 41) or PtDA intervention (n = 41). Feasibility outcome results were (1)
      referral rate at approximately 20/month, (2) recruitment rate 61%, and (3)
      successful delivery of PtDA and study management. Pre-consultation, PtDA patients
      scored lower on the DCS scale (mean, standard deviation [SD] 27.3 (18.4) compared
      to usual care, 49.4 (18.6); the between-group difference in means [95% confidence
      interval (CI)] was - 22.1[- 30.23, - 13.97]. A difference remained post
      implantation 21.2 (11.7), PtDA intervention 29.9 (13.3), and usual care - 8.7 [-
      14.61, - 2.86]. SURE test results supported DCS differences. The PtDA group
      scored higher on the ICD-related knowledge questions, with 47.50% scoring greater
      than 3/5 of the knowledge questions correct, compared to 23.09% receiving usual
      care. The mean [SD] number of correct knowledge responses out of 5 was 3.33(1.19)
      in the PtDA group and 2.62 (1.16) in usual care pre-implant. Concordance between
      values and decision choice found a strong association between predicted and
      actual ICD implant status in the intervention group. Conclusion: Our results
      suggest that a future definitive trial is feasible. The ICD-specific PtDA shows
      promise with respect to preliminary estimates of differences in outcomes. Trial
      registration: NCT01876173.

PMID- 29201390
TI  - Caring for Caregivers (C4C): study protocol for a pilot feasibility randomised
      control trial of Positive Written Disclosure for older adult caregivers of people
      with psychosis.
AB  - Background: The caregivers of people who experience psychosis are themselves at
      risk of developing physical and mental health problems. This risk is increased
      for older adult caregivers who also have to manage the lifestyle and health
      changes associated with ageing. As a consequence, older adult caregivers are in
      particular need of support; we propose a Written Emotional Disclosure (WED)
      intervention, called Positive Written Disclosure (PWD). Methods/design: This is a
      pilot randomised controlled trial of PWD compared to a neutral writing control
      and a no writing condition. We aim to recruit 60 participants, 20 in each arm.
      This study will utilise a mixed-methods approach and collect quantitative
      (questionnaires) and qualitative (interviews) data. Quantitative data will be
      collected at baseline and 1, 3, and 6 months post baseline. Participants who
      complete a writing task (PWD or neutral writing control) will be invited to
      complete an exit interview to discuss their experiences of the intervention and
      study. The study is supported by a patient and public involvement group.
      Discussion: The results of this trial will determine whether a definitive trial
      is justified. If so, the quantitative and qualitative findings will be used to
      refine the intervention and study protocols. Trial registration: ISRCTN,
      ISRCTN79116352. Registered on 23 January 2017.

PMID- 29201391
TI  - The effect of obesity on intraoperative complication rates with hysteroscopic
      compared to laparoscopic sterilization: a retrospective cohort study.
AB  - Background: Surgical sterilization is a common method of contraception. There
      have been few studies evaluating the effect of obesity on procedural
      complications with either laparoscopic or hysteroscopic methods of sterilization.
      The purpose of this study was to compare the incidence of intraoperative
      complications of hysteroscopic tubal occlusion with laparoscopic tubal ligation
      among obese and nonobese women. Methods: This retrospective cohort study compared
      women undergoing interval laparoscopic or hysteroscopic sterilization in the
      operating room between September 2009 and December 2011 at a single hospital.
      Serious complications included: unintended surgery, uterine perforation,
      anaphylaxis, blood transfusion, infection requiring antibiotics, hospital
      admission, fluid overload, myocardial infarction, and venous thromboembolism.
      Post-operative events included: nausea/vomiting, doctor evaluation or additional
      pain medication required in the recovery room, and emergency department visit
      within 2 weeks of surgery. The association between sterilization type and
      incidence of complications was examined overall, separately by BMI group, and
      also among patients who received general anesthesia. Results: A total of 433
      laparoscopic and 277 hysteroscopic procedures were reviewed. The BMI distribution
      of the sample was 35 % normal weight, 31 % overweight, and 34 % obese which is
      comparable to the general US female population. No life-threatening events were
      identified. Serious complications were similar with 20 (4.6 %) in the
      laparoscopic group and 11 (4.0 %) in the hysteroscopic group (p = 0.9). The most
      common serious complications were bleeding from the tube, cervical laceration,
      and uterine perforation. Although not statistically significant, women with a BMI
      of 30 or greater had only 1 (1 %) serious complication in the hysteroscopic group
      compared to 7 (5.2 %) in the laparoscopic group. Postoperative events were
      increased in the laparoscopic group (16.2 %) compared to the hysteroscopic group
      (6.9 %), especially among overweight and obese women (p <0.01). Failure to
      complete the intended bilateral occlusion occurred for 14 women in the
      hysteroscopic group compared to just one woman in the laparoscopic group (p
      <0.001). Conclusion: Both laparoscopic and hysteroscopic tubal sterilization are
      safe with few serious complications based on these data. No cases of laparotomy,
      blood transfusion, or life-threatening events were identified. There was no
      difference in serious complication rate by sterilization method. Overweight and
      obese women were no more likely to experience a serious complication with either
      method than women with a BMI <25. There were fewer postoperative events (p <0.01)
      with hysteroscopic sterilization, but far fewer failed laparoscopic procedures (p
      <0.001). These study findings can be used to enhance sterilization counseling.

PMID- 29201392
TI  - Trends in contraceptive practices among women in reproductive age at a health
      facility in Ghana: 2011-2013.
AB  - Background: There is dearth of information on contraceptive use among women in
      reproductive age in Ghana over time. This study sought to examine the trends in
      contraceptive practices among women in reproductive age in a health facility in
      Ghana in terms of acceptor rates, age at first reporting and couple-years of
      protection. Methods: The contraceptive data of women were extracted from the
      registry of a health facility for a three-year period from 2011 to 2013. Graphs
      and tables were used to present the trends in the use of various contraceptive
      methods for the study period. Results: Depot Medroxyprogesterone Acetate (Depo
      Provera) was the most accepted contraceptive method as well as the most
      protective method against unwanted pregnancies for the three-year period.
      However, male condom, estradiol valerate/norethindrone enanthate (Norigynon) and
      pills were the lowest among all the contraceptives used by women for the study
      period in terms of acceptance, while intra-uterine device had the lowest couple
      years of protection. Conclusions: Some contraceptive methods have been
      consistently under-utilised by women in the catchment area and needed to be
      promoted to improve upon the contraceptive use rate.

PMID- 29201393
TI  - Medical student simulation training in intrauterine contraception insertion and
      removal: an intervention to improve comfort, skill, and attitudes.
AB  - Background: Opportunities for medical students to place intrauterine
      contraception (IUC) in patients are rare. Our objective was to determine whether
      participation in an IUC insertion and removal simulation exercise would increase
      medical students' comfort level with, attitudes towards, and willingness to
      recommend IUC. Methods: A prospective cohort study was undertaken in all students
      completing the obstetrics and gynecology clerkship at a major academic hospital
      during the 2010-2011 academic year. The exposure consisted of a 45-minute
      interactive didactic session and a 30-minute, hands-on practicum in IUC placement
      and removal using medical instruments and realistic pelvic models. Both
      levonorgestrel and Cu380A IUC devices were utilized. Participants completed a pre
      and post-simulation survey instrument, designed to examine students' IUC
      specific knowledge, comfort, and attitudes. Pre- and post-simulation responses
      were compared by McNemar's test for paired samples. Results: Thirty-five paired
      pre- and post-simulation surveys were analyzed, representing a 78 % response
      rate. Composite IUC-related knowledge scores increased by a median of 3 out of 10
      points after the intervention (p < 0.01). Students were significantly more
      comfortable counseling patients about IUC as well as inserting IUC after the
      intervention, compared to before. Seven (20 %) students before, compared to 27
      (77 %) after, agreed with the statement, "I feel comfortable placing an IUC in a
      patient under the supervision of an experienced doctor" (p < 0.01). Students
      developed significantly more favorable attitudes towards IUC through the
      intervention. Nineteen (54 %) participants before, compared to 27 (77 %) after,
      agreed with the statement, "I would recommend an IUC to my family member" (p =
      0.02). Conclusions: A hands-on simulation during the obstetrics and gynecology
      clerkship increased medical students' knowledge of and comfort with IUC and
      resulted in more favorable attitudes toward the method. Intrauterine
      contraception simulation in medical curricula may help expand utilization of this
      effective contraceptive method.

PMID- 29201394
TI  - LARC methods: entering a new age of contraception and reproductive health.

PMID- 29201395
TI  - Health knowledge, attitudes and practices of family planning service providers
      and clients in Akwapim North District of Ghana.
AB  - Background: Family planning services help save lives by reducing women's exposure
      to risks of child birth and abortion. While family planning services provide
      measures to prevent unintended pregnancies and time the formation of families,
      the acceptability and coverage is still very low worldwide. Some of the reasons
      for this include poor quality of service, unavailability of range of methods,
      fear of opposition from partners, side effects and health concerns among
      others.About 40 % of the world's 215,000 annual deaths in childbirth occur in the
      Sub-Saharan region. In Ghana, urban-rural fertility differences range from two to
      three children. The acceptability and coverage of family planning are still low
      and in the study area in particular. Methods: We sought to examine factors that
      contribute to low acceptability and coverage of family planning services in a sub
      urban community with a design of quantitative cross-sectional. Ethical approval
      was given by the Ghana Health Service. Midwives and community health nurses who
      provide family planning services were interviewed. Exit-interview was also
      conducted with women receiving a variety of outpatient services. Results: Most of
      the women in this study (48.7 %) were in the 25-34 age range and were either
      married (42.8 %) or cohabiting (40.5 %). Majority of these women (67.7 %) have
      middle/Junior high level of formal education with a modal parity of two. Sixty
      eight (68) clients were identified as current family planning users. About 6.0 %
      and 4.5 % were dissatisfied about auditory and visual privacy during counselling
      respectively. This was confirmed by providers who attributed it to inappropriate
      facility layout. Most of the clients (79.1 %) were not given educational
      materials although 88.8 % were talked to about family planning and this could be
      due to unavailability of these hand-outs.Though clients show satisfaction of
      services received, providers did not follow standard protocols with as much as
      73.7 % faced with challenges in provision of services which were attributed to
      improper facility layout and lack of furniture. About 77.2 % were willing to
      provide short term methods, while 91.2 % wanted to provide long term methods. As
      much as 93.3 % of the women said they would have liked providers give more
      detailed information on family planning. While most of the women (88.3 %) used
      injectables, only 6.1 % and 0.9 % used Implants and IUD respectively.
      Conclusions: Finding ways to improve client privacy through good facility layout
      will ensure visual and auditory privacy to enhance family planning service
      provision and uptake. Continuous competency training will assist providers design
      innovative action plans and meet client satisfaction needs.

PMID- 29201396
TI  - A novel approach to postpartum contraception: a pilot project of Pediatricians'
      role during the well-baby visit.
AB  - Background: Postpartum women are at high risk of unintended pregnancy as many do
      not receive timely postpartum contraception. Utilization of routine postpartum
      care varies widely. Conversely, the Well-Baby Visit (WBV) for newborns is highly
      utilized and provides an opportunity to discuss contraception with mothers. This
      project aimed to test the feasibility and acceptability of having pediatric
      residents administer a simplified Reproductive Life Plan Tool (RLPT) with
      postpartum women during routine infant care. Methods: Pediatric resident
      physicians used the RLPT with mothers of infants 16-weeks of age or less during
      WBVs. The RLPT prompts physicians to ask general questions about women's
      contraceptive needs and offer referral services for mothers who desire
      contraception services. Residents participated in a feedback session and survey
      to assess acceptance and perceived feasibility of using the RLPT during routine
      care. Results: Pediatric residents completed 50 RLPTs. Seventeen percent of
      eligible women accepted a referral to contraception services. During feedback
      sessions, pediatric residents (n = 18) reported comfort implementing the
      intervention and acceptance of the RLPT for discussing contraception. Concerns
      included limited time during the WBV and the potential to shift focus away from
      infant. On a post-intervention survey (n = 14), 92.9 % of physicians reported
      comfort in using the RLPT, and 71.4 % reported that the tool was easily
      understood although findings were varied regarding ease of implementing a RLPT in
      practice. Conclusions: Findings indicate that use of the RLPT is generally
      feasible during routine infant care and acceptable to pediatric resident
      physicians with recognition of challenges to implementation. Acceptance of a
      referral was low among postpartum women in this pilot study.

PMID- 29201397
TI  - Characteristics and contributory factors for injectable contraceptive usage among
      women in Kumasi, Ghana.
AB  - Background: Preferred methods of contraception vary from country to country.
      Family Planning services have been available on a large scale in Ghana since the
      1980's and their use has contributed to gradual decline in the total fertility
      rate from 6.4 in 1988 to 4.2 in 2014. Since their introduction in Ghana in the
      early 1990's, Injectable contraceptives have seen increasing patronage and are
      currently the most preferred method of contraception. We set out to identify
      possible factors contributing to the preference for injectable contraceptives
      among women in Ghana. Methods: We conducted a descriptive cross-sectional survey
      of women accessing contraceptive services at the Family Planning Unit of the
      Komfo Anokye Teaching Hospital in Kumasi, Ghana. Women who reported for the
      second dose of their injections were eligible to be selected for participation in
      the study. Informed consent was obtained from eligible participants. Data was
      collected using a structured questionnaire in January and February 2011. Data
      captured included age, marital status, highest level of education completed,
      religion, ethnicity and employment status, previous contraceptive use, sources of
      contraceptive information and reasons for choosing injectable contraceptives.
      Quantitative data was entered into a Microsoft Access Database and analysed using
      Epi Info Version 7.1.4. Qualitative data was analysed thematically. Results: A
      total of 247 respondents participated in the study. One hundred and seventy three
      (70.0 %) were using Depot Medroxyprogesterone Acetate and 74 (30.0 %) were using
      NorethisteroneEnanthate/Estradiol Valerate. The mean age for women on Depot
      Medroxyprogesterone Acetate was higher than those on
      NorethisteroneEnanthate/Estradiol Valerate (p < 0.001). The effectiveness of
      method, recommendation from other users, low incidence of forgetfulness and the
      relatively longer intervals for administration were the commonest reasons for the
      use of injectables among respondents. The majority of users, 225 (91.1 %), were
      satisfied with the method and will recommend it to other potential users. Only
      10.8 % of the 68 respondents reporting undesirable effects of the injectables
      intend to change the method. Conclusion: A high level of satisfaction exists
      among current users of injectables in Ghana and is influenced by a variety of
      factors. Strategies to increase the uptake of injectables can go a long way to
      increase the contraceptive prevalence rate and reduce the unmet need for Family
      Planning in Ghana.

PMID- 29201398
TI  - The yield of endometrial aspiration in women with various risk factors and
      bleeding abnormalities.
AB  - Background: Even in the face of a substantial increase in the numbers of
      endometrial cancer cases and in the numbers of women who have risk factors, there
      is no clear agreement about the indications for assessing the endometria of women
      with abnormal bleeding or about the tools to use in that assessment. This study
      sought to determine in a group of high risk women with abnormal uterine bleeding,
      the probability that an outpatient endometrial aspiration would identify
      significant pathology. Methods: Retrospective cohort study of the histology from
      endometrial aspirations performed from 2001 to 2008 for abnormal uterine bleeding
      at Harbor-UCLA Medical Center and its satellite public health clinics. Medical
      records were reviewed in detail to assess risk factors, descriptions of bleeding
      abnormalities and histologic results. Results: The charts of 1601 women who
      underwent 1636 endometrial biopsies for a wide variety of abnormal uterine
      bleeding patterns yielded 73 (4.6 %) cases of endometrial carcinoma, 43 cases of
      atypical endometrial hyperplasia (2.7 %), for an overall yield of significant
      pathology of 7.2 %. Hyperplasia without atypia was found in another 83 cases (5.2
      %). Obesity, diabetes and postmenopausal age are associated with an increased
      risk of significant pathology. Bleeding patterns were so poorly documented that
      analysis of yield by this factor should be viewed with caution. Conclusions: The
      probability of detecting significant uterine pathology is greatest among obese,
      diabetic postmenopausal women with diabetes (26.3 %). Conversely, the probability
      of identifying significant pathology in younger women without risk factors is
      less than 2 %. For women who perceive their individualized risk estimate to be
      too small to justify an endometrial biopsy, it may be possible to offer oral
      higher dose progestin therapy on the condition that persistent abnormal bleeding
      will require more intensive evaluation. These estimates of absolute risk of being
      diagnosed with significant pathology on endometrial biopsy may be helpful to
      patients as they consider giving informed consent for the procedure.

PMID- 29201399
TI  - Renewing focus on family planning service quality globally.
AB  - Reducing the global unmet need for contraception is currently a priority for many
      governments, multi-lateral initiatives, non-governmental organizations, and
      donors. Evidence strongly suggests that the provision of quality family planning
      services can increase uptake, prevalence, and continuation of contraception.
      While an accepted framework to define the components of family planning service
      quality exists, translating this framework into assessment tools that are
      accessible, easily utilized, and valid for service providers has remained a
      challenge. We propose new approaches to improve the standardization and
      accessibility of family planning service quality assessment tools to simplify
      family planning service quality evaluation. With easier approaches to program
      evaluation, quality improvements can be performed more swiftly to help increase
      uptake and continuation of contraception to improve the health of women and their
      families.

PMID- 29201400
TI  - Elective single embryo transfer- the power of one.
AB  - Despite the highest historical live birth success rates for couples undergoing in
      vitro fertilization (IVF), there has been an epidemic of iatrogenic twin and
      higher order gestation conceived from this treatment. Continued improvement in
      cryopreservation techniques have allowed preservation of supernumerary embryos
      for use in future cycles, and refinements in culture systems and embryo selection
      have resulted in the transfer of fewer embryos while maintaining favorable
      pregnancy rates. The voluntary transfer of a single high quality embryo, elective
      single embryo transfer (eSET), has significantly reduced multiple gestation rates
      and maximized the rate of singleton pregnancy without compromising overall
      success rates. Although eSET is the standard of care in several developed
      countries, utilization in the United States has been slow. States with mandated
      IVF insurance have seen decreases in preterm birth rates yielding down stream
      health care savings. Herein, the evolution and future applications of this
      practice to reduce the risk of iatrogenic twins is reviewed.

PMID- 29201401
TI  - Identification and potential role of telocytes in human uterine leiomyoma.
AB  - Background: Telocytes are specialized interstitial tissue cell type. Our aim is
      to characterize telocytes in human uterine leiomyoma (ULM) and its adjacent
      myometrium (Myo-F) as well as normal myometrium (Myo-N). Methods: ULMs and Myo-F
      tissues were taken from hysterectomy specimens done to treat symptomatic uterine
      fibroids (N = 20). Myo-N is isolated from hysterectomies done on ULM- free uteri
      for other benign indications (N = 15).Telocytes were detected using
      immunohistochemistry to detect c-Kit (CD-117), as a surface marker expressed on
      telocytes, and electron microscopic examination to identify telocytes
      characteristic ultrastructure. Cellular count and electron microscopic features
      of telocytes in each of the studied tissues were compared. Results: Telocytes
      could be detected in ULMs, Myo-F and Myo-N using c-KIT immunostaining. Electron
      microscopy confirmed the presence of telocytes in the three types of tissues
      identifying their characteristic features including small triangular or fusiform
      cell bodies with extensive cellular prolongations. ULM telocytes showed
      ultrastructural features suggestive of high cellular activities. Cell counts of
      ULM telocytes (3.35 +/- 0.39) were significantly higher (P value = 0.00039) than
      that of Myo-F (1.39 +/- 0.13). Myo-N (2.6 +/- 0.36) contained higher telocyte
      numbers than Myo-F (1.39 +/- 0.13), but the difference did not reach statistical
      significance (P value = 0.19). Conclusions: Telocytes are detected in higher
      numbers and activity in ULMs than Myo-F or Myo-N. In ULMs, telocytes can work as
      a hormonal sensors for stem cells, provide scaffold for newly formed myocytes, or
      control important downstream signaling pathways.

PMID- 29201403
TI  - The effect of home exercise on ovulation induction using clomiphene citrate in
      overweight underserved women with polycystic ovarian syndrome.
AB  - Background: Age-adjusted rates of obesity are reported to be 35.8 % among US
      adult women and 49 % in some race/ethnicity, underserved populations. (1).
      Underserved populations often have less access to weight-loss intervention
      options and are at high risk for obesity related problems including anovulation,
      infertility, pregnancy-related complications and adverse long-term health
      outcomes. (2). The purpose of this study was to evaluate a home exercise plan
      using a pedometer on weight loss, ovulation induction and pregnancy rates in our
      overweight and obese underserved clinic population. Methods: Twenty one
      overweight (BMI >= 25-29.9) and obese I-II (BMI >= 30-39.9) 18-42 years old were
      recruited. Participants received an exercise/nutrition questionnaire at the
      initiation and completion and called weekly for 4 weeks. Ten participants were
      randomly assigned to the home exercise program (PedGp). PedGp received a
      pedometer, daily step-count goal, and were called to increase goal by 50 %
      weekly. All participants then underwent clomiphene stair-step ovulation
      induction. All study participants were referred to the University Wellness Clinic
      for diet and exercise counseling. Results: There were high percentages of women
      with co-morbidities in both groups including fatty liver, low vitamin D,
      hyperlipidemia, hypothyroidism, prediabetes and diabetes.1. Those completing the
      4-week home program increased baseline steps by 21.2 % weekly. Only 3/10 women
      reached at least one weekly goal of 50 % increase. Although the goal was rarely
      met, participants who completed study had increased number of daily steps.2.
      Greater number in PedGp lost weight or stayed the same (5/10 vs. 2/11).3. Greater
      number in PedGp spontaneously ovulated (4/10 vs. 1/11) or became pregnant (4/10
      vs. 3/11). (not statistically significant due to small sample size). Conclusion:
      There are high percentages of comorbidities in this population. Although the goal
      was rarely met, participants who completed study had increased number of daily
      steps. A greater number in PedGp lost weight or stayed the same. A greater number
      in PedGp spontaneously ovulated or became pregnant (not statistically significant
      due to small sample size). Importantly, 40 % of women who lost weight became
      pregnant. This is highly encouraging and suggests that the development of
      pedometer interventions may prove a cost effective option. Weight loss programs
      for this population hold promise and efficient hospital or community-based
      programs may prove beneficial.

PMID- 29201402
TI  - Association between contraceptive implant knowledge and intent with implant
      uptake among postpartum Malawian women: a prospective cohort study.
AB  - Background: Long-acting reversible contraception (LARC) can assist women with
      birth spacing and reduce unintended pregnancies. Sub-Saharan Africa has low
      uptake of the two available methods of LARC, the subdermal implant and
      intrauterine contraception (IUC). Our primary objectives were to: 1) calculate
      the incidence of LARC use among postpartum Malawian women, and 2) assess if LARC
      knowledge and intent to use LARC were associated with LARC uptake. Methods: This
      study was a prospective cohort study of 634 postpartum women who were recruited
      from the postpartum ward of Bwaila Hospital in Lilongwe, Malawi. Study
      participants completed a baseline survey in the postpartum ward. Follow-up
      telephone surveys about contraceptive use were conducted at 3, 6, and 12 months
      postpartum. Cox proportional hazards regression analysis was performed to
      evaluate if implant knowledge and intent to use implant were associated with
      implant uptake. Results: One hundred thirty-seven implant and 10 IUC placements
      were reported over 12 months of follow-up; given the low rate of IUC uptake,
      further analysis was only done for implant uptake. The incidence rate for implant
      uptake was 35.6 per 100 person-years (95 % CI 30.0, 42.2). Correct implant
      knowledge (adjusted HR = 1.69; 95 % CI 1.06, 2.68) and intent to use implant
      (adjusted HR 1.95; 95 % CI 1.28, 2.98) were both associated with implant uptake.
      Conclusions: More women reported implant use than IUC use in our study. Correct
      implant knowledge and intent to use implant were both associated with implant
      uptake, with a stronger association for intent. Interventions to increase LARC
      uptake should focus on improving LARC knowledge and removing barriers to LARC.
      Trial registration: Clinical Trial Registration #: NCT01893021.

PMID- 29201404
TI  - Young peoples' interface with providers of contraceptive care: a simulated client
      study in two Ugandan districts.
AB  - Background: Young people in Uganda have a large unmet need for modern
      contraception, and the reasons are unclear. This study describes young peoples'
      experiences of contraceptive care, client-provider interactions and its aftermath
      on choice, access and satisfaction. Methods: Simulated client method, with 128
      encounters with providers in public and private health care facilities was used.
      Semi-structured narrative debriefing and a structured questionnaire were used to
      collect data. Content analysis, descriptive and inferential statistics were
      applied. Results: Both qualitative and quantitative results highlight favorable
      reception, provider bias, low client satisfaction and reservations about
      contraceptive methods. Two thirds of the providers choose a contraceptive method
      for the client. The clients reported satisfaction with contraceptive services in
      29 % of the consultations. Privacy was reported to be observed in 42 % and
      clients felt respectfully treated in 50 % of the consultations. However, most
      clients would not recommend the visited facility to others. Client-provider
      interactions revealed contradictory views on methods to use, whether to first
      have children, and whether to use contraceptives at all. Younger clients seemed
      to be treated differently than older clients; contraceptives were provided after
      a prolonged debate. Inaccurate information about contraceptives was provided and
      costs were high. Providers conveyed potential adverse effects of contraceptives
      to young people in a way that indicated providers own fears and doubts.
      Conclusion: Young people are not able to exercise their rights to choose, obtain
      and use contraceptives when needed. Overall satisfaction with the services was
      rated low and client- provider interactions were often unfavorable.

PMID- 29201405
TI  - The CROWN Initiative: journal editors invite researchers to develop core outcomes
      in women's health.
AB  - ?.

PMID- 29201406
TI  - The affordable care act and family planning services: the effect of optional
      medicaid expansion on safety net programs.
AB  - Background: Title X of the Public Health Service Act provides funding for a range
      of reproductive health services, with a priority given to low-income persons. Now
      that many of these services are provided to larger numbers of people with low
      income since the passage of the Affordable Care Act and Medicaid expansion,
      questions remain on the continued need for the Title X program. The current
      project highlights the importance of these safety net programs. Methods: To help
      inform this policy issue, research was conducted to examine the revenue and
      service changes for Title X per state and compare those findings to the states'
      Medicaid expansion and demographics. The dataset include publicly available data
      from 2013 and 2014 Family Planning Annual Reports (FPAR). Paired samples
      differences of means t-tests were then used to compare the means of family
      planning participation rates for 2013 and 2014 across the different categories
      for Medicaid expansion states and non-expansion states. Results: The ACA has had
      an impact on Title X services, but the link is not as direct as previously
      thought. The findings indicate that all states' Title X funded clinics lost
      revenue; however, expansion states fared better than non-expansion states.
      Discussion: While the general statements from the FPAR National surveys certainly
      are supported in that Title X providers have decreased in number and scope of
      services, which has led to the decrease in total clients, these variations are
      not evenly applied across the states. The ACA has very likely had an impact on
      Title X services, but the link is not as obvious as previously thought.
      Conclusion: Title X funded clinics have helped increase access to health
      insurance at a greater rate in expansion states than non-expansion states. There
      was much concern from advocates that with the projected increased revenue from
      Medicaid and private insurance, that Title X programs could be deemed
      unnecessary. However, this revenue increase has yet to actually pan out. Title X
      still helps fill a much needed service gap for a vulnerable population.

PMID- 29201407
TI  - Long-acting family planning method switching among revisit clients of public
      health facilities in Dire Dawa, Ethiopia.
AB  - Background: "Contraceptive switching" from one method to another is a common
      phenomenon. Switching from a more effective long-acting method to a less
      effective method exposes women for unplanned pregnancy. The aim of this study was
      to assess the level and factors associated with long-acting family planning
      method switching to other methods. Method: A facility-based cross-sectional study
      was conducted from January to March 2013 on 634 women attending public health
      facilities in Dire Dawa City Administration, Ethiopia. Participants of the study
      were revisit clients of family planning service and were interviewed as they
      appear in the clinics. Data were analyzed using crude and adjusted logistic
      regression, and results were reported using OR and corresponding 95 % CI.
      Results: Long-acting family planning method switching among revisit clients was
      40.4 %; switching from implant was 29.8 % and from IUCD, it was 10.6 %. The main
      reasons for methods switching were side effects of the methods such as bleeding,
      weight loss, and feeling of arm numbness. The tendency of switching was less
      among married women (AOR = 2.41, 95 % CI: 1.01, 5.74), women who had 2-4 and 5
      and more children (AOR 3.00, 95 % CI: 1.59, 5.67) and (AOR 2.07, 95 % CI: 1.17,
      3.66), respectively. It was also less among women who want to stop birth (AOR
      5.11, 95 % CI: 1.15, 24.8), among those who mentioned health care providers as
      source of information for family planning (AOR 1.88, 95 % CI: 1.18, 3.01), and
      among women whose husbands were aware of their use of the methods (AOR 3.05, 95 %
      CI: 1.88, 4.94). Conclusions: Method switching from long-acting contraceptives to
      less effective methods is high. Method switching was significant among unmarried
      women, who had one child, plan to postpone fertility, and whose husbands were not
      aware of their wive's use of the method. In the provision of family planning
      service, the health care providers should give adequate information about each
      method and risks of method switching. Appropriate family planning Information
      Education and Communication (IEC) and Behavioral Change Communication (BCC)
      strategies should be emphasized.

PMID- 29201408
TI  - Effect of performance based financing home visiting on the use of modern methods
      of contraception in the kumbo east health district, Cameroon.
AB  - Background: The use of modern methods of contraception (MMC) as defined by the
      World Health Organization still remains a challenge in most of Sub-Saharan
      Africa. Performance Based Financing (PBF) home visit was introduced in 2012 to
      increase the use of those modern methods in the Kumbo East Health District
      (KEHD), Cameroon.We determined the utilization rates of MMC in areas in the KEHD
      with PBF home visits compared with those areas with no home visits. Methods: This
      was a cross sectional study carried out in the KEHD during the period February 1
      to May 31, 2015. A multistage cluster sampling method was used to recruit 262 and
      221 women aged 15-49 years in the intervention and nonintervention health areas,
      respectively. A structured, closed ended questionnaire was used. Results: The
      average age of women was similar in both groups 30.40 (SD 8.57); median 30 years
      in the intervention group and 30.49 (SD 7.84); median 30 years in controls. Most
      participants in the intervention health area (60.3 %) used modern methods of
      contraception compared to 46.6 % of those in the control group (aOR: 1.75 %; 95 %
      CI: 1.212.53) and the most commonly used MMC was medroxyprogesterone in the
      intervention group and condoms in the control area. Conclusion: Utilization of
      MMC was significantly higher in the area with PBF home visits than in areas
      without that service. While this indicates that the intervention has benefit,
      there may be other contributing factors.

PMID- 29201409
TI  - Knowledge, attitude and practice GAP in family planning usage: an analysis of
      selected cities of Uttar Pradesh.
AB  - Background: The GAP between the knowledge of contraception and its actual
      practice is well recognized in the literature of family welfare studies. The
      present study assessed the relation between the level of knowledge and practice
      of contraception among the women and sought to explore the reasons behind the
      Knowledge, Attitude, and Practice - GAP (KAP GAP) regarding contraceptive users
      in six cities of Uttar Pradesh. Method: Present analysis based on 17,643
      currently married women aged 15 to 49. A Bivariate analysis (chi2 test) and a
      multivariable logistic regression were performed for the study. Result: The
      highest percentages of respondents (women) were in the age group 35-49 (40-45 %)
      in all the districts considered. Knowledge of contraceptives was almost
      universal; tubal ligation and pill were the commonly known methods. Information
      about the contraceptive methods was mostly obtained through the husband. In the
      present study, there was a highly significant association (p < 0.01) of age
      group, educational status of respondents, the number of living children, the
      wealth of the respondent, media exposure and husband's education with the
      variable KAP GAP for all six cities. Health concern issues in all the districts
      were the most prominent reason for not using contraception. Conclusion: There
      differences in the socioeconomic and demographic factors exist, which lead to KAP
      GAP in the family planning (FP) usages. Therefore, in designing effective family
      planning programme, there is a need to understand the various factors which
      influence the practice of contraception.

PMID- 29201410
TI  - Barriers and facilitators to implementing a patient-centered model of
      contraceptive provision in community health centers.
AB  - Background: The Contraceptive CHOICE Project developed a patient-centered model
      for contraceptive provision including: (1) structured, evidence-based counseling;
      (2) staff and health care provider education; and (3) removal of barriers such as
      cost and multiple appointments to initiate contraception. In preparation for
      conducting a research study of the CHOICE model in three community health
      settings, we sought to identify potential barriers and facilitators to
      implementation. Methods: Using a semi-structured interview guide guided by a
      framework of implementation research, we conducted 31 qualitative interviews with
      female patients, staff, and health care providers assessing attitudes, beliefs,
      and barriers to receiving contraception. We also asked about current
      contraceptive provision and explored organizational practices relevant to
      implementing the CHOICE model. We used a grounded theory approach to identify
      major themes. Results: Many participants felt that current contraceptive
      provision could be improved by the CHOICE model. Potential facilitators included
      agreement about the necessity for improved contraceptive knowledge among patients
      and staff; importance of patient-centered contraceptive counseling; and benefits
      to same-day insertion of long-acting reversible contraception (LARC). Potential
      barriers included misconceptions about contraception held by staff and providers;
      resistance to new practices; costs associated with LARC; and scheduling
      challenges required for same-day insertion of LARC. Conclusions: In addition to
      staff and provider training, implementing a patient-centered model of
      contraceptive provision needs to be supplemented by strategies to manage patient
      and system-level barriers. Community health center staff, providers, and patients
      support patient-centered contraceptive counseling to improve contraception
      provision if organizations can address these barriers.

PMID- 29201411
TI  - Desire for birth spacing or limiting and non-use of long acting and permanent
      contraceptive methods among married women of reproductive age in Aksum Town,
      North Ethiopia.
AB  - Background: Long acting and permanent contraceptive methods are the most
      effective family planning (FP) methods to prevent pregnancy and thereby averting
      adverse consequences of too many and ill-timed pregnancies. However, long acting
      and permanent contraceptive methods (LAPMs) are underutilized in Ethiopia for
      little documented reasons. Therefore, this study is aimed to assess magnitude and
      factors associated with desire for birth spacing for at least 2 years or limiting
      child bearing and non-use of LAPMs among married women of reproductive age in
      Aksum town, Northern Ethiopia. Methods: A community-based cross-sectional study
      was conducted in Aksum town, North Ethiopia from May to June, 2015 among 779
      randomly selected married women of reproductive age. Data were collected using
      interviewer administered pre-tested questionnaire. Data were entered using Epi
      Info version 6.04 and exported to SPSS version 16 for analysis. Multivariate
      logistic regression models were fitted to identify factors associated with desire
      for birth spacing or limiting and not using LAPMs. Results: The total desire for
      birth spacing or limiting was 69 % and amongst those women 85.2 % were not using
      LAPM. Education, occupation, husband's attitude towards LAPMs, age, number of
      pregnancy, regular media exposure and decider on the number of children to bear
      were significantly associated with desire for birth spacing or limiting.
      Moreover; education, occupation, husband's attitude towards LAPMs, discussion on
      family planning with husband, knowledge, attitude and intention to use LAPMs were
      significantly associated with not using LAPMs. Conclusion: Desire for birth
      spacing or limiting and not using LAPMs is very high in the study area.
      Therefore, increasing access to family planning information and services with
      special emphasis on LAPMs and male involvement in the program are very important.

PMID- 29201413
TI  - High-risk sexual behaviors while on depot medroxyprogesterone acetate as compared
      to oral contraception.
AB  - Background: Depot medroxyprogesterone acetate (DMPA) contraceptive use is
      associated with an increased risk for Chlamydia infection. However, prior studies
      inadequately account for potential differences in sexual behavior between users
      of DMPA and users of other contraceptive methods. In this study we compare sexual
      risk-taking behavior in women using DMPA to women using oral contraceptive pills
      (OCP) to assess risk of Chlamydia trachomatis infection. Methods: In this cross
      sectional study of 630 reproductive-aged women seeking routine gynecologic care
      (449 OCP and 181 DMPA users) sexual risk-taking was evaluated by use of the Safe
      Sex Behavior Questionnaire, a validated measure of sexual behaviors and
      attitudes. All women were screened for Chlamydia. Logistic regression estimated
      the association of contraceptive choice, sexual behaviors, and Chlamydia
      infection. Results: Oral contraceptive pill users differed from DMPA users in
      age, race, marital status, education level, and pregnancy history (p-values all
      <0.05). Oral contraceptive pill users had used their method of contraception for
      longer average duration (p < 0.01) and reported greater frequency of condom use
      (p < 0.01). Eleven (2.5%) OCP and 2 (1.1%) DMPA users had Chlamydia (p = NS).
      Conclusions: Oral contraceptive pill and DMPA users differed with respect to both
      demographic factors and frequency of condom use. Odds of current Chlamydia
      infection did not differ between OCP and DMPA users when controlling for sexual
      risk-taking or demographic factors, though due to low Chlamydia rates in our
      population, this study was underpowered to detect this difference.

PMID- 29201412
TI  - Recent developments have made female permanent contraception an increasingly
      attractive option, and pregnant women in particular ought to be counselled about
      it.
AB  - Background: Despite the increased prevalence of reversible contraception, global
      unintended pregnancy rates are stable. Mistakes, method failures, side effects,
      alcohol, stock-outs, fears, costs, delays, myths, religious interference, doctors
      with other priorities, traditions and lack of health professionals may all factor
      in. Yet these unintended pregnancies - nearly a hundred million annually - cause
      much individual suffering, and in the long run, can aggravate conflicts, poverty,
      forced emigration and climate change. Presently, non-poor women postpone
      childbearing because of longer educational trajectories and careers.
      Sterilisations are therefore less often regretted or coerced. For poor-resourced
      women with a completed family, an unwanted pregnancy often has serious
      consequences, including crossing the (extreme) poverty line in the wrong
      direction, choosing an unsafe abortion, or even death. Caesarean sections (CSs),
      which currently stand at around 23 million annually, are increasing. On an
      "intention-never-to-become-pregnant-again" analysis, choosing a partial, and even
      more so a total bilateral tubectomy to be implemented during an - anyway
      performed - CS is by far the most reliable and safe contraceptive choice compared
      to meaning to start female or male sterilisation or any other contraceptive
      method later, and it reduces the chance of a future ovarian carcinoma
      substantially. CSs make subsequent pregnancies more dangerous. Simultaneously,
      they provide convenient, potentially cost-free opportunities for voluntary
      permanent contraception (PC): particularly important if there is no guaranteed
      future access to reliable contraception, safe abortion and well-supervised
      labour. Partial solution: Millions of women are within reach of attaining freedom
      from the "tyranny of excessive fertility" when they have a CS. Therefore, any
      woman who might conceivably be of the firm opinion that her family will be (over)
      completed after delivery should antenatally have "what if you have a CS"
      counselling to assess whether she would like a tubectomy/ligation. Yet many are
      not provided with this option: leading to frequent regret, more often than having
      been giving that choice would. Conclusion: Withholding antenatal counselling
      about the option of PC for in case the delivery might become a CS is very
      prevalent, yet often more medically risky, and morally questionable than when,
      even in labour, a doctor sometimes decides in the absence of earlier counselling,
      considering numerous factors, to provide the choice to undergo a concurrent
      sterilisation if s/he is convinced that would be in the patient's best interest.

PMID- 29201414
TI  - Determinants of contraceptive use among Nigerian couples: evidence from the 2013
      Demographic and Health Survey.
AB  - Background: Nigeria remains a focus for increasing contraceptive use, as it is
      one of the most populous countries in Sub-Saharan Africa. The objective of the
      current study was to investigate determinants of contraceptive use in Nigeria
      couples. Methods: Using the 2013 Nigeria Demographic and Health Survey, we
      estimated the likelihood of contraceptive use based on concordance with male
      partner desire for family size, male and female fertility preferences, female
      decision making power, and male partner attitudes toward contraceptive use.
      Results: Male partner perception that decisions regarding health should be made
      jointly or primarily by women was positively associated with use. Women were less
      likely to use contraceptives in couples in which male partners had greater
      earning power. Finally, men who viewed contraceptives as an enabler for
      promiscuity had female partners less likely to use contraceptives. Conclusions:
      These findings highlight the importance of male partners in women's contraceptive
      decision making.

PMID- 29201415
TI  - Contraceptive utilization and associated factors among women of reproductive age
      group in Southern Nations Nationalities and Peoples' Region, Ethiopia: cross
      sectional survey, mixed-methods.
AB  - Background: Though contraceptive utilization has comprehensive benefit for women,
      it was one of underutilized public intervention in Ethiopia and in the study
      area. Thus, assessing status and factors affecting contraceptive utilization
      among women of reproductive age group was found key step for program improvement.
      Methods: Community based cross-sectional study was conducted from March to April,
      2015 in Southern Nations and Nationalities Peoples' Region, Ethiopia. A
      multistage stratified cluster sampling method was used to select 3205 study
      subjects. Study used both quantitative and qualitative methods. Statistical
      Package for Social Sciences version 20 was used to analyze quantitative data. The
      association between variables was determined using odds ratio at 95% confidence
      interval. Results: Contraceptive utilization was 53.3% among women of
      reproductive age groups. Nearly three fourth, (73.6%), of current users were
      using short-term contraceptive methods. Factors associated with contraception
      utilization were overall knowledge of and attitude towards contraceptives, age,
      residence, number of alive children, experience of child death, marital status
      and deciding number of children. Contraceptive utilization was also affected by
      various misconceptions. Conclusion: Contraceptive utilization was below national
      Health Sector Development Program IV target. Program implementers need to address
      socio-cultural barriers. Gender myths and specific roles and power inequalities
      that can function as a barrier to contraceptive utilization should be assessed.

PMID- 29201416
TI  - Determinants of abortion among clients coming for abortion service at felegehiwot
      referral hospital, northwest Ethiopia: a case control study.
AB  - Background: According to the World Health Organization (WHO) estimate, one-third
      of pregnancies end in miscarriage, stillbirth, or induced abortion in the world.
      There are various reasons for a woman to seek induced abortion. However, limited
      information is available so far in the country and particularly in the study
      area. Therefore, the aim of the current study was to identify the determinants of
      induced abortion among clients coming for abortion care services at Bahirdar
      Felegehiwote referral hospital, Northwest Ethiopia. Methods: Institutional based
      unmatched case-control study was conducted from September to December 2014.
      Interview administered questioner was used to collect primary data. Enumeration
      and systematic random sampling (K = 3) method was used to select 175 cases and
      350 controls. A binary logistic regression model was fitted to identify
      determinant factors. Odds ratio with 95% CI was computed to assess the strength
      and significance of the association. Result: All sampled cases and controls were
      actually interviewed. The likelihood of abortion was higher among non-married
      women [AOR: 18.23, 95% CI: 8.04, 41.32], students [AOR: 11.46, 95% CI: 6.29,
      20.87], and women having a monthly income of less than 500 ETB [AOR: 11.46, 95%
      CI: 6.29, 20.87]. However, the likelihood of abortion was lower among women age
      greater than 24 years [AOR: 0.29, 95% CI: 0.11, 0.79] and who had the previous
      history of induced abortion [AOR: 0.31, 95% CI: 0.15, 0.65]. Conclusion: The
      study identified being non-married, student, women age less than 24 years, having
      the previous history of induced abortion, and low monthly income as an
      independent determinant of induced abortion. Interventions focused on the
      identified determinant factors are recommended.

PMID- 29201417
TI  - Cancer survivors of gynecologic malignancies are at risk for decreased
      opportunity for fertility preservation.
AB  - Background: Cancer survivors rate fertility as one of the most important
      determinants of their quality of life in the years after cancer treatment. We
      seek to describe the reproductive goals of women affected by gynecologic cancers
      and investigate their specific challenges during fertility preservation (FP)
      counseling. Methods: Univariate & multivariate logistic regression were used for
      quantitative analysis of objective FP counseling measures between women with
      gynecologic (GYN) and non-gynecologic (non-GYN) cancers from a cross sectional
      survey. Framework analysis was conducted on patient perception of physician
      patient interactions. Results: Of the 2537 women contacted, 1892 responded and
      1686 reported treatment with potential to impact fertility. Among women with GYN
      cancers 52% wanted future children. Women <35 years were interested in FP (74%).
      Women with Gyn cancers received less FP counseling than women with non Gyn cancer
      (OR 0.5 95% CI 0.4-0.6). Three hundred twenty-four patients gave qualitative
      answers. Patient identified barriers included incomplete FP information (59%),
      nondisclosure (29%), a disinterest in FP (5%), and a perceived urgency to start
      treatment (7%). Conclusions: Women with gynecologic cancers are less likely to be
      counseled about FP in comparison to women not affected by gynecologic cancers
      despite having similar fertility goals. We have identified patient perceived
      barriers to optimal FP counseling which may be improved upon to increase the
      value of FP and optimize quality of life for cancer survivors of gynecologic
      malignancies.

PMID- 29201418
TI  - Factors associated with contraceptive use among sexually active Nepalese youths
      in the Kathmandu Valley.
AB  - Background: In Nepal, evidence is sparse regarding the use of contraception at
      first and current relationships among sexually active young people. This study
      examined the factors associated with modern contraceptive use at first and
      current sexual relationships. Methods: A descriptive cross-sectional household
      survey conducted amongst young Nepalese men and women living in the urban areas
      of the Kathmandu valley. We used logistic regression to model the relationship
      between selected independent variables and outcome variables (use at first sexual
      intercourse and current use of modern contraception) among 492 ever sexually
      active youth aged 15-24 years. Results: We found that the key factors associated
      with current non-use of modern contraceptives among sexually active youth age 15
      24 were young age at first sexual contact and a relationship with someone other
      than a spouse, while significant factor associated with current use of
      contraception was religion, revealing that Hindu youths having lower odds of use
      compared to young people who belonged to other religions. Conclusions: The
      findings suggest that contraception education should be intensified and directly
      towards those entering adolescence to encourage youths to adopt contraception at
      the time of their first sexual relationship. The influence of religion on use of
      modern contraception needs further exploration.

PMID- 29201419
TI  - Patterns of postpartum contraceptive use among Somali immigrant women living in
      Minnesota.
AB  - Background: The postpartum period is a crucial time to provide family planning
      counseling and can decrease incidence of adverse reproductive outcomes. The
      purpose of this study was to characterize patterns of postpartum contraception
      and to investigate long acting reversible contraceptive (LARC) use among Somali
      women living in a metropolitan area of Minnesota in an effort to provide better
      family planning and reproductive health counseling in this growing immigrant
      population. Methods: A retrospective chart review was conducted of Somali women
      who delivered between January 1, 2011 and December 31, 2014. Information was
      collected regarding family planning counseling provided and contraceptive methods
      chosen at the postpartum clinic visit. Results: Of the 747 Somali women who
      delivered during this time period, 56.4% had no postpartum follow up visit. At
      the postpartum visit, 88.3% of women received family planning counseling and
      80.8% chose a contraceptive method with the remainder declining. The intrauterine
      device (IUD) was the most popular contraceptive method, chosen by 39.7% of women.
      Other than parity, no statistically significant differences were observed between
      women who chose LARC versus other contraceptive methods. Of the women that chose
      a LARC, 39.4% had it placed at the time of their postpartum visit; immediate
      placement was statistically significantly more likely with more recent delivery,
      lower BMI and obstetrician as the provider type. Conclusions: The IUD was the
      most popular method of postpartum contraception. There was a trend toward
      increase in LARC use with increasing parity. Same-day LARC placement was
      uncommon, but should be encouraged in this population given high loss to follow
      up rate.

PMID- 29201420
TI  - Knowledge, acceptance and utilisation of the female condom among women of
      reproductive age in Ghana.
AB  - Background: The female condom (FC) is the only safe and effective female
      initiated method that provides simultaneous protection against unintended
      pregnancy as well as sexually transmitted infections (STIs), including HIV/AIDS.
      Knowledge of FC use among women and the perceptions and attitudes towards condom
      use can contribute to its uptake as an important public health strategy for HIV
      prevention in Ghana. However, there is a dearth of empirical evidence in this
      area of public health research to inform interventions. This study seeks to
      examine women's knowledge, acceptance and utilisation of the FC and factors that
      influence its acceptance and utilisation. Methods: A descriptive cross-sectional
      survey design was used and a total of 380 females between the ages of 15 and 49
      years were sampled from the Hohoe Municipality of the Volta Region, Ghana. A self
      administered structured questionnaire measuring the study variables was used, and
      frequencies, percentages and Chi Square tests were used to analyse the data.
      Results: There is low level of FC use among the women as less than half (48.4%)
      of the sample were aware of the FC. It was further observed that 21.1, 21.8 and
      11.1% of the sample reported friends, media and a public lecture as their sources
      of knowledge of the FC respectively. It was also observed that there is a low
      level of FC acceptance and utilisation, and also limited access to the FC from
      nearby shops/pharmacies (1.8%) and health centres (7.4%). Conclusions: There is a
      generally low level of FC awareness, knowledge, acceptance and utilisation and
      therefore, there is the need for increased public education on the FC and its
      benefits to women in preventing unwanted pregnancies and sexually transmitted
      diseases (STDs).

PMID- 29201421
TI  - Process evaluation of a mobile phone-based intervention to support post-abortion
      contraception in Cambodia.
AB  - Background: The MObile Technology for Improved Family Planning (MOTIF) trial
      assessed a mobile phone-based intervention comprising voice messages and
      counsellor support to increase post-abortion contraception at four Marie Stopes
      International clinics in Cambodia. The aim of this process evaluation was to
      assess participants' interaction with the intervention from a service provider
      perspective. Methods: (1) We conducted a descriptive analysis to assess
      participants' interaction with the intervention. (2) In order to explore how the
      intervention might work, we assessed associations between interaction with the
      intervention and contraception use using logistic regression analysis. (3) We
      undertook a logistic regression analysis to assess associations between baseline
      socio-demographic factors and ever requesting to speak to a counsellor (pressing
      '1'), a variable found to be associated with contraception use. Results: Amongst
      249 women that received six interactive voice messages +/- counsellor support for
      contraception, around half actively requested to speak to a counsellor (pressed
      '1') and over 90% spoke to a counsellor at some stage. Women who spoke to the
      counsellor having requested to (by pressing '1') were more than four times as
      likely to be using effective contraception at four months compared to women who
      didn't request or speak to the counsellor (Odds Ratio 4.39; 95% CI: 1.15-16.71).
      There was a small, non-statistically significant increase in contraception use
      amongst women that spoke to the counsellor without requesting a call. Increased
      parity, a history of >2 previous induced abortions, lower socio-economic status,
      and medical abortion (after adjusting for age, socio-economic status and
      residence) were associated with requesting to speak to a counsellor. Conclusions:
      The interactive message can identify a subgroup of women in whom counselling will
      be more effective and appears to be equitable in terms of engaging those most in
      need. The intervention could be adapted based on the findings of this study.

PMID- 29201422
TI  - Demographic analysis of a low resource, socioculturally diverse urban community
      presenting for infertility care in a United States public hospital.
AB  - Background: Infertility is a prevalent disease of reproductive health that exerts
      an impact on an estimated 80 million people worldwide. For many, involuntary
      childlessness becomes a central and preoccupying issue in their lives, the impact
      of which is exacerbated by lack of access to basic care and treatment. These
      effects maybe further magnified among immigrant communities, a growing but highly
      marginalized population that has been shown in other areas of reproductive health
      to experience worse health outcomes and delays in access to care. To date, few
      studies have examined the unique medical and sociocultural considerations of
      infertility among immigrant populations in the United States. Methods: Our study
      is a cross-sectional analysis of women presenting for infertility evaluation at a
      county hospital serving a low resource, socioculturally diverse largely immigrant
      communities in comparison to infertile women from a largely affluent population
      presenting to a high resource, comprehensive fertility center. We employed
      surveys to evaluate demographics and socioeconomic parameters as well as
      abstracted data from medical records to obtain infertility diagnoses.
      Multivariate regression analysis was applied to examine impact of sociocultural
      factors as predictors of duration of untreated infertility disease burden
      experienced by patients. Results: Eighty-seven women were included in our
      analysis. In the county hospital/low resource clinic (LR), the mean age was 32.9
      +/- 4.9 vs 36.4 +/- 6.3 years in the fee-for-service/high resource clinic (HR).
      The mean reported duration of infertility in LR and HR patients was 3.4 +/- 3.0
      vs 2.3 +/- 1.5 years. 70% of LR patients were monolingual non-English speakers vs
      5.4% of HR patients. 59% of LR patients reported an annual household income of
      less than $25,000 and 70% did not have a college degree. 81.1% of HR patients
      reported an income of higher than $100,000, and 81.1% had completed college or
      graduate school. The most common infertility diagnosis in the LR was anovulation
      (38%) and tubal factor (28%) compared to diminished ovarian reserve (37.8%) and
      male factor (51.4%) in the HR. After controlling for age at the initiation of
      pregnancy attempt, lower education level, lower income, and immigrant status were
      significantly correlated with a longer duration of infertility. Conclusions:
      Women presenting for infertility care to a low resource county medical center
      represent immigrant communities and are generally of younger age, but with a
      longer duration of infertility. This study identifies lower educational level,
      income, and immigrant status as barriers in access to care.

PMID- 29201423
TI  - Patient satisfaction and wait times following outpatient manual vacuum aspiration
      compared to electric vacuum aspiration in the operating room: a cross-sectional
      study.
AB  - Background: Outpatient manual vacuum aspiration (MVA) is a safe and equally
      effective alternative to electric vacuum aspiration (EVA) in the operating room.
      This project was conducted to determine whether outpatient MVA expedites care
      while maintaining patient satisfaction. Methods: A cross-sectional study of a
      convenience sample of patients undergoing surgical management of spontaneous
      abortion, induced abortion, or retained products of conception with either
      outpatient MVA under local anesthesia or EVA in the operating room was conducted.
      Of 138 women completing surveys, 48 (34.8%) underwent outpatient MVA and 90
      (65.2%) underwent EVA in the operating room. Procedure length, time from decision
      to procedure, and patient satisfaction were assessed through a self-administered
      questionnaire completed post-procedure. Results: Most (77%) patients in the MVA
      group reported waiting fewer than 2 h from the time of their decision to the
      procedure, while most (74%) EVA patients reported waiting over 12 h (P < 0.001);
      the MVA group reported higher satisfaction with time to procedure (P = 0.02). The
      median procedure length was significantly shorter in the EVA group (10 vs. 20
      min, P < 0.001). There was no significant difference between groups in overall
      satisfaction with the procedure (P = 0.16). Conclusion: Outpatient MVA under
      local anesthesia is a suitable alternative to operating room-based EVA for
      management of spontaneous abortion, induced abortion, and retained products of
      conception. Outpatient MVA is associated with shorter decision-to-procedure time
      and is highly acceptable to patients. Integration of outpatient MVA into clinical
      settings can add time- and resource-saving options for uterine evacuation while
      maintaining a positive patient experience.

PMID- 29201424
TI  - Women's perceptions of contraceptive efficacy and safety.
AB  - Background: Adoption of contraceptive implants and intrauterine devices has been
      less than might be expected given their superior efficacy and convenience. The
      purpose of this study was to assess knowledge and beliefs held by women, which
      may influence their contraceptive choices and theirongoing utilization of
      contraceptive methods. Methods: English speaking, nonpregnant, reproductive-age
      women, who were not surgically sterilized, were individually interviewed to
      obtain limited demographic characteristics and to assess their knowledge about
      the efficacy of various contraceptive methods in typical use and about the
      relative safety of oral contraceptives. Results: A convenience sample of 500
      women aged 18-45 years, with education levels that ranged from middle school to
      postdoctoral level was interviewed. The efficacy in typical use of both combined
      oral contraceptives and male condoms was correctly estimated by 2.2%; over two
      thirds of women significantly overestimated the efficacy of each of those methods
      in typical use. Oral contraceptives were thought to be at least as hazardous to a
      woman's health as pregnancy by 56% of women. Conclusions: The majority of
      reproductive aged women surveyed substantially overestimated the efficacy of the
      two most popular contraceptive methods, often saying that they were 99%
      effective. Women with higher education levels were most likely to overestimate
      efficacy of oral contraceptives. Women of all ages and education levels
      significantly overestimated the health hazards of oral contraceptives compared to
      pregnancy. Overestimation of effectiveness of these methods of contraception, may
      contribute to lower adoption of implants and intrauterine devices. When
      individualizing patient counselling, misperceptions must be identified and
      addressed with women of all educational backgrounds. Trial registration: Not
      applicable.

PMID- 29201426
TI  - Unmet need for modern contraceptives and associated factors among women in the
      extended postpartum period in Dessie town, Ethiopia.
AB  - Background: The contraceptive use of women in the extended postpartum period is
      usually different from other times in a woman's life cycle due to the additional
      roles and presence of emotional changes. However, there is lack of evidence
      regarding women contraceptive need during this period and the extent they met
      their need. Therefore, the objective of this study was to assess unmet need for
      modern contraceptives and associated factors among women during the extended
      postpartum period in Dessie Town, North east Ethiopia in December 2014. Methods:
      A community-based cross-sectional study was conducted among women who gave birth
      one year before the study period. Systematic random sampling technique was
      employed to recruit a total of 383 study participants. For data collection, a
      structured and pretested standard questionnaire was used. Descriptive statistics
      were done to characterize the study population using different variables.
      Bivariate and multiple logistic regression models were fitted to control
      confounding factors. Odds ratios with 95% confidence intervals were computed to
      identify factors associated with unmet need. Results: This study revealed that
      44% of the extended post-partum women had unmet need of modern contraceptives of
      which 57% unmet need for spacing and 43% for limiting. Education of women (being
      illiterate) (AOR (adjusted odds ratio) =3.37, 95% CI (confidence interval) 1.22
      7.57), antenatal care service (no) (AOR = 2.41, 95% CI 1.11-5.79), Post-natal
      care service (no) (AOR = 3.63, CI 2.13-6.19) and knowledge of lactational
      amenorrhea method (AOR = 7.84 95% CI 4.10-15.02) were the factors positively
      associated with unmet need modern contraceptives in the extended postpartum
      period. Conclusion: The unmet need for modern contraception is high in the study
      area. There is need to improve the quality of maternal health service, girls
      education, information on postpartum risk of pregnancy on the recommended
      postpartum contraceptives to enable mothers make informed choices of
      contraceptives.

PMID- 29201425
TI  - Heavy menstrual bleeding diagnosis and medical management.
AB  - Heavy menstrual bleeding (HMB) is a common gynecological problem that has a
      significant impact on a woman's quality of life and the activities of daily
      living. Due to the difficulty in accurately describing menstrual bleeding
      abnormalities using older terminology, the PALM-COEIN classification system of
      the Federation Internationale de Gynecologie et d'Obstetrique was proposed to
      describe and identify the etiology of abnormal endometrial bleeding. As there is
      no single pathway that is associated with HMB, there are several therapeutic
      interventions involving different molecular pathways to reduce HMB. This article
      will highlight the current evidence as it relates to the etiology of HMB as well
      as medical modalities of treatment.

PMID- 29201427
TI  - Predictors of long acting and permanent contraceptive methods utilization among
      Women in Rural North Shoa, Ethiopia.
AB  - Background: According to available evidence, one in three married women in
      Ethiopia tends to avoid multiple children. On the other hand, women using Long
      Acting and Permanent Contraceptive Methods (LAPMs) are just 5 %. So, we aimed at
      identifying the factors associated with the utilization of LAPMs. Methods: We
      conducted a community based unmatched case control study among married women
      living in the rural areas of North Shoa zone, Ethiopia, in March 2015. The cases
      were married women using LAPMs, while controls were married women who were using
      modern short term methods. We recruited a total sample of 406 married women for
      this study on a 1:1 case to control ratio basis. We collected the data through
      interview using a pre tested questionnaire, and then a logistic regression model
      was fitted to the data to examine factors associated with the utilization of
      LAPMs. Adjusted Odds Ratio (AOR) with the corresponding 95% confidence interval
      was computed. Results: In our study, women whose husbands were daily laborers
      [AOR; 95% CI: 4.4(1.23,15.72)], who had $85-$140 monthly household income [AOR;
      95% CI: 1.8(1.10,3.14)], and who were aged less than 20 years and below when they
      gave the first birth [AOR; 95% CI: 1.78, 4.90) were more likely to use LAPMs
      compared to women whose husbands were government employees, who had less than $85
      monthly household income, and who were aged 20 years and above when they gave
      first child. Conclusion: We found that husbands' characteristics were more
      important than their wives characteristics in influencing women's utilization of
      LAPMs though such husband characteristics considered in this study were few in
      number. So, we recommend further research to examine the different
      characteristics of husbands responsible for women's utilization of LAPMs.

PMID- 29201429
TI  - Side effects and the need for secrecy: characterising discontinuation of modern
      contraception and its causes in Ethiopia using mixed methods.
AB  - Background: Contraceptive discontinuation is a major barrier to reducing global
      unmet needs for family planning, but the reasons why women discontinue
      contraception are poorly understood. Here we use data from Ethiopia to
      investigate (i) the magnitude of contraceptive discontinuation in 2005-2011, (ii)
      how the risk of discontinuation varies with method type and education level and
      (iii) the barriers to continuation. Our main hypothesis is that contraceptive
      discontinuation is driven by the experience of physiological side-effects
      associated with the use of hormonal contraception, rather than a lack of formal
      education. Methods: We used a mixed methods explanatory sequential design to
      explain the quantitative results in more details through the qualitative data.
      First, we analysed quantitative data from the 2011 Ethiopian Demographic and
      Health Survey to study patterns of contraceptive discontinuation and method
      choice using multilevel multiprocess models. Second, we conducted semi-structured
      interviews and focus group discussions in the 3 most populated regions of
      Ethiopia with individuals of reproductive age and health professionals. Results:
      The analysis of EDHS data shows that the rate of discontinuation has not reduced
      in the period 2005-2011 and remains high. Discontinuation mainly takes the form
      of abandonment, and is a function of method type, age and wealth but not of
      educational level. Interviews with women and health professionals reveal that the
      experience of debilitating physiological side effects, the need for secrecy and
      poverty are important barriers to continuation. Conclusions: Our findings
      together suggest that physiological and social side-effects of contraceptive use,
      not a lack of formal education, are the root causes of contraceptive abandonment
      in Ethiopia.

PMID- 29201430
TI  - Evaluation of the challenges faced in increasing contraceptive access within a
      community college population.
AB  - Background: Research demonstrates removing barriers to access, decreasing costs
      and offering same-day placement of long-acting reversible contraception (LARC)
      increases contraceptive uptake in young women. For those in community college
      (CC), LARC utilization might reduce the risk of dropout and improve degree
      completion. We identified a local school who had documented an unmet need for on
      campus services through a recent student assessment. We then established an on
      campus, same day contraceptive clinic at the CC as part of a clinical trial. We
      found that students did not use the service even after multiple attempts to
      increase awareness and we ended the study. Here, we report lessons learned from
      attempting research in this environment in addition to results from a follow-up
      survey to determine why students did not access the clinical resource. Students
      reported that they already had good access to contraception and preferred to get
      their healthcare off-campus. This study demonstrates the complexities of studying
      highly focused interventions to influence access to care in the current health
      care environment with ever changing regulations. Trial registration: NCT02735551
      . Registered April 6, 2016.

PMID- 29201428
TI  - Effect of aging on the female reproductive function.
AB  - Aging is a complex biological process that involves the accrual of bodily changes
      over a long life span. In humans, advanced maternal age is associated with
      infertility and adverse pregnancy complications. Cellular and organic senescence
      is hypothesized to contribute to the age-related decline in reproductive
      function. Accumulating evidence suggests that immune cells play pivotal roles in
      physiological reproductive function and pregnancy. The concept of "inflammaging"
      has recently emerged- an age-dependent, low-grade, chronic, and systemic
      inflammatory state induced by the senescence-associated secretory phenotype
      (SASP), which is produced by the innate immune, parenchymal, and nonparenchymal
      cells within the organs. In the present review, we discuss how cellular
      senescence and inflammaging accelerate reproductive failure in women by promoting
      SASP and immune-senescence during the establishment of pregnancy. In addition, we
      discuss the role of immune cells and their senescence in reproductive function,
      particularly in the ovaries (the corpus luteum), oviduct, and uterus.

PMID- 29201431
TI  - Indicators of young women's modern contraceptive use in Burkina Faso and Mali
      from Demographic and Health Survey data.
AB  - Background: High total fertility rates in Burkina Faso and Mali are leading to
      population growth beyond the agricultural and fiscal means of its citizens.
      Providing access to affordable family planning methods is a key step in driving
      the demographic transition where fertility and mortality rates decline.
      Furthermore, both nations face significant challenges as climate change is
      projected to disproportionately impact the western Sahel region undermining
      environmental, social and economic stability within the region. This analysis was
      included in formative research to inform family planning programming. The aim of
      this study was to examine possible indicators of long acting and permanent
      contraceptive method (LAPM) and short-term method (STM) use for young women in
      Burkina Faso and Mali. Methods: Secondary data analysis was conducted using the
      three most recent Demographic and Health Survey (DHS) datasets for Burkina Faso
      (1998, 2003, 2010) and Mali (2001, 2006, 2012). Women ages 15-24, at risk for
      unwanted pregnancy were included in these analyses. Summary descriptive
      statistics across all time points are reported and multinomial logistic
      regression was used with the most recent data to determine potential indicators
      of different types of modern contraceptive methods. Results: In Burkina Faso in
      2010, 24% of women ages 15-24 were using modern contraceptives. Only 2.9%
      reported using LAPMs in 2010, an increase from 0.3% in 1998. In Mali, modern
      contraceptive use increased more recently, rising from 9.4% in 2001 to 10.2% in
      2006 to 15.3% in 2012. LAPM use also increased from 0.3% in 2001 to 4.1% in 2012.
      Significant indicators of LAPM contraceptive use in both countries included
      educational attainment, ideal family size, home ownership and husband's desire
      for more children. Conclusions: Young women in Burkina Faso and Mali are
      increasingly using modern contraceptives for family planning; however, the LAPM
      contraceptive prevalence rate remains low. Our analysis indicates that social
      norms around ideal family size for both men and women continue to drive young
      women's choices around family planning and impede use of LAPMs. To increase
      modern contraceptive use and curb fertility rates, local governments and
      development organizations should focus on women's empowerment and include male
      partners.

PMID- 29201432
TI  - Tube construction by a tanaidacean crustacean using a novel mucus secretion
      system involving the anal opening.
AB  - Background: Animals in diverse aquatic groups construct tubes using mucus and
      filaments, and the acquisition of this capability has likely played an important
      role in the evolution and diversification of small benthic animals. Tanaidacea is
      a crustacean order that includes tube-constructing species, most of which belong
      to Tanaidoidea and Paratanaoidea, with a few in Kalliapseudidae (Apseudoidea).
      Two previously reported systems used in tube construction are the thoracic-gland
      system, with secretory glands in thoracic segments (pereonites), and the
      pereopodal-gland system, with glands in pereopods. Results: Parapseudidae
      (Apseudoidea) also includes a tube-constructing species, Parapseudes algicola
      (Shiino, 1952), which lacks large secretory glands in all pereonites and
      pereopods, but has a pair of acinar glands in the pleotelson, lateral to the gut.
      Each gland connects to the gut via a short duct, and thence to the exterior via
      the anal opening. Secretions released from these glands are used to construct
      tubes, and contain acidic and neutral mucopolysaccharides. Conclusion: We report
      in P. algicola a third, novel secretory system, here termed the pleotelsonal
      gland system, used for tube construction in Tanaidacea. It is similar to the
      secretory system in some "thalassinidean" decapods; both systems have secretory
      glands connecting to the gut and thence to the anal opening as the outlet;
      however, these gland systems likely evolved independently. Recent discoveries of
      novel secretory systems for tube construction in Tanaidacea suggest that
      information from smaller, less well-known groups will be necessary to understand
      how acquisitions of tube-constructing capability affected diversification in
      animals.

PMID- 29201433
TI  - Heart regeneration in the salamander relies on macrophage-mediated control of
      fibroblast activation and the extracellular landscape.
AB  - In dramatic contrast to the poor repair outcomes for humans and rodent models
      such as mice, salamanders and some fish species are able to completely regenerate
      heart tissue following tissue injury, at any life stage. This capacity for
      complete cardiac repair provides a template for understanding the process of
      regeneration and for developing strategies to improve human cardiac repair
      outcomes. Using a cardiac cryo-injury model we show that heart regeneration is
      dependent on the innate immune system, as macrophage depletion during early time
      points post-injury results in regeneration failure. In contrast to the transient
      extracellular matrix (ECM) that normally accompanies regeneration, this
      intervention resulted in a permanent, highly cross-linked extracellular matrix
      scar derived from alternative fibroblast activation and lysyl-oxidase enzyme
      synthesis. The activation of cardiomyocyte proliferation was not affected by
      macrophage depletion, indicating that cardiomyocyte replacement is an independent
      feature of the regenerative process, and is not sufficient to prevent fibrotic
      progression. These findings highlight the interplay between macrophages and
      fibroblasts as an important component of cardiac regeneration, and the prevention
      of fibrosis as a key therapeutic target in the promotion of cardiac repair in
      mammals.

PMID- 29201434
TI  - Influence of longitudinal position on the evolution of steady-state signal in
      cardiac cine balanced steady-state free precession imaging.
AB  - Background: Emerging quantitative cardiac magnetic resonance imaging (CMRI)
      techniques use cine balanced steady-state free precession (bSSFP) to measure
      myocardial signal intensity and probe underlying physiological parameters. This
      correlation assumes that steady-state is maintained uniformly throughout the
      heart in space and time. Purpose: To determine the effects of longitudinal
      cardiac motion and initial slice position on signal deviation in cine bSSFP
      imaging by comparing two-dimensional (2D) and three-dimensional (3D)
      acquisitions. Material and Methods: Nine healthy volunteers completed cardiac MRI
      on a 1.5-T scanner. Short axis images were taken at six slice locations using
      both 2D and 3D cine bSSFP. 3D acquisitions spanned two slices above and below
      selected slice locations. Changes in myocardial signal intensity were measured
      across the cardiac cycle and compared to longitudinal shortening. Results: For 2D
      cine bSSFP, 46% +/- 9% of all frames and 84% +/- 13% of end-diastolic frames
      remained within 10% of initial signal intensity. For 3D cine bSSFP the
      proportions increased to 87% +/- 8% and 97% +/- 5%. There was no correlation
      between longitudinal shortening and peak changes in myocardial signal. The
      initial slice position significantly impacted peak changes in signal intensity
      for 2D sequences (P < 0.001). Conclusion: The initial longitudinal slice location
      significantly impacts the magnitude of deviation from steady-state in 2D cine
      bSSFP that is only restored at the center of a 3D excitation volume. During
      diastole, a transient steady-state is established similar to that achieved with
      3D cine bSSFP regardless of slice location.

PMID- 29201435
TI  - Endothelial nitric oxide synthase gene polymorphisms in patients with slow
      coronary flow.
AB  - Background and aims: The aim of this study was to explore potential associations
      of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms
      of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow
      (SCF). The association between plasma nitrate and nitrite (NO x ) concentrations
      and eNOS gene polymorphisms was also assessed. Materials and methods: The intron
      4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated
      DNA blood samples obtained from the SCF patient group (n = 30) and healthy group
      consisted of age- and sex-matched controls (n = 61). Results: Plasma NO x level
      was significantly lower in patients with SCF than in controls. In addition,
      patients with SCF have significantly lower nitric oxide levels than control
      subjects within each genotype variants. The allele and genotyped frequencies of
      the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with
      SCF and the controls. Plasma NO x concentrations with respect to the relevant
      genotypes were found insignificant. Discussion and conclusion: Plasma NO x is
      lower in patients with SCF than in healthy subjects. Our findings may suggest the
      lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS
      gene and SCF.

PMID- 29201436
TI  - Therapeutic benefits of phosphodiesterase-5 inhibition in chronic heart failure:
      A meta-analysis.
AB  - Background: Phosphodiesterase-5 inhibitors (PDE5i) have been shown to be
      beneficial for patients with pulmonary arterial hypertension. However, several
      studies would have documented a useful effect of PDE5i even for pulmonary
      hypertension secondary to left-sided chronic heart failure (CHF). Methods: We
      performed a meta-analysis including randomized controlled trials (RCTs) which had
      compared PDE5i (mostly sildenafil) and placebo in CHF patients. Results: Fourteen
      studies enrolling a total of 928 patients were incorporated in the meta-analysis.
      In heart failure with reduced left ventricular ejection fraction (HFREF), PDE5i,
      compared to placebo, significantly improved the composite of death and
      hospitalization (OR = 0.28; 95% CI: 0.10-0.74). They also improved peak VO2
      [difference in means (MD): 3.76; 95% CI: 3.27-4.25], six-minute walking distance
      test (MD: 22.7 m; 95% CI: 8.19-37.21), and pulmonary arterial systolic pressure
      (MD: -11.52 mmHg; 95% CI: -15.56 to -7.49). Conversely, in CHF with preserved
      left ventricular ejection fraction (HFpEF), PDE5i proved not to yield any
      significant improvement of the investigated outcomes. Conclusions: In HFREF,
      PDE5i showed beneficial effects on the composite of death and hospitalization, as
      well as on exercise capacity and pulmonary hemodynamics. Conversely, in HFpEF, no
      significant clinical, spiroergometric, or hemodynamic improvement was achieved
      using PDE5i therapy.

PMID- 29201438
TI  - Pathomorphological peculiarities of tuberculous meningoencephalitis associated
      with HIV infection.
AB  - Background and aims: One of the most severe manifestation displays of
      tuberculosis (TB) generalization is meningitis/meningoencephalitis. The purpose
      of this work was to improve the diagnostic efficiency of TB central nervous
      system (CNS) affection in human immunodeficiency virus (HIV)-infected persons.
      Materials and methods: Meninges and cerebral tissues, taken from died patients,
      who were HIV-infected and dead from TB of CNS affection, were investigated
      histologically. Results and discussion: Our examination showed that clinical
      course of the pathologic process loses the peculiarity of TB-undulating
      character, and changes in tissues have monomorphism that appears in the presence
      of the same type of granulomas with a few Pirogov-Langhans cells. Alterative
      reactions with formation of the large fields of caseous necrosis, necrotic
      focuses, areas of infiltration with polymorphic cellular elements went out on the
      first plan in the disorder of cerebrum in patients with the terminal stage of HIV
      infection. The tendency to decrease in inflammatory-proliferative processes was
      observed, which is confirmed by the presence of the poorly expressed cellular
      reaction on the peripheries of focuses of caseous necrosis. Conclusion:
      Morphologic features of tuberculous meningoencephalitis in HIV-infected patients
      are the presence of edema, gliosis, trombovasculitis, small focal hemorrhage,
      tuberculous granuloma formation with a small number of Pirogov-Langhans cells,
      and the prevalence of alterative-exudative reactions.

PMID- 29201437
TI  - Impact of a multicomponent hand hygiene intervention strategy in reducing
      infection rates at a university hospital in Saudi Arabia.
AB  - Background and aims: Few studies have reported the correlation between hand
      hygiene (HH) practices and infection rates in Saudi Arabia. This work was aimed
      to study the effect of a multicomponent HH intervention strategy in improving HH
      compliance and reducing infection rates at King Fahd Hospital of the University,
      Al-Khobar, Saudi Arabia between January 2014 and December 2016. Methods: A
      yearlong multicomponent HH intervention, which included various strategies
      recommended by the World Health Organization, was introduced. HH compliance among
      staff and infection rates observed in the inpatient wards were assessed and
      compared at pre- and post-interventional phases. Results: There was a significant
      increase in mean HH compliance from 50.17% to 71.75% after the intervention (P <
      0.05). Hospital-acquired infection (HAI) and catheter-associated urinary tract
      infection (CAUTI) rates decreased from 3.37 to 2.59 and from 3.73 to 1.75,
      respectively (P < 0.05). HH compliance was found to be negatively correlated with
      HAI (r = -0.278) and CAUTI (r = -0.523) rates. Conclusions: Results show that
      multicomponent intervention is effective in improving HH compliance, and that an
      increase in HH compliance among hospital staff decreases infection rates. Further
      studies on cost-effectiveness of such a model could augment to these findings.

PMID- 29201439
TI  - Management of an acute ischemic stroke during thrombolytic treatment in a
      pregnant patient with prosthetic valve thrombosis.
AB  - Prosthetic valve thrombosis (PVT) is a life-threatening complication in pregnant
      women with mechanical prosthetic heart valves. Thrombolytic therapy (TT) has
      evolved as an effective treatment alternative to surgery, which is associated
      with very high maternal and fetal mortality and morbidity in these patients.
      Acute ischemic stroke may rarely occur during TT for PVT. Here, we present a
      pregnant patient who was complicated with cerebral thromboembolism during TT for
      PVT and successfully managed with continuation of TT.

PMID- 29201440
TI  - Evaluation of ghrelin levels and endothelial functions in patients with coronary
      slow flow phenomenon.
AB  - Background: Ghrelin has recently been reported to have beneficial effects on
      cardiac contractile functions and coronary blood flow. The main purpose of this
      study was to investigate the role of ghrelin in the pathogenesis of coronary slow
      flow (CSF) together with endothelial functions. Methods: Twenty-five patients
      having normal coronary arteries with CSF and 25 controls with normal coronary
      flow were included into the study. The quantitative measurement of coronary blood
      flow was performed for each coronary artery using the thrombolysis in myocardial
      infarction (TIMI) frame count (TFC) method. Ghrelin levels were measured using
      the enzyme-linked immunosorbent assay method from venous blood samples.
      Endothelial functions were evaluated from the brachial artery with the flow
      mediated dilation (FMD) and nitrate-related dilation methods. Results: There was
      a significant difference in terms of mean TFC values between the control and CSF
      groups (p < 0.001 for all coronary arteries). The mean FMD percentage among
      patients with CSF was lower than that of the control group (5.9 +/- 0.8 vs. 10.7%
      +/- 1.1%; p < 0.001). A moderate negative correlation was observed between the
      FMD percentages and the TFCs. There was no relationship between the TFC and
      ghrelin levels. Conclusion: Plasma ghrelin levels seem to be uninfluential while
      impaired endothelial functions play an important role in the etiopathogenesis of
      CSF.

PMID- 29201441
TI  - Sex differences of odontometrical indexes crowns of molars.
AB  - Modern reconstructive methods of dentistry (stopping, restoration, and
      prosthetics with different types of orthopedic constructions) require detailed
      examination of the anatomical structure of the teeth crowns, especially
      examination of the knowledge about the relief of masticatory surface. That is
      why, we conducted a detailed examination of the features of odontoglyphics of
      molars, according to the sex and determination the odontometrical teeth indices
      of the citizens of Ternopil region. To achieve the goals, we use the following
      research methods, such as odontological, odontometrical, and statistical.
      According to the odontometrical indices of the sizes of the crowns of the molars,
      women's processes of reduction are reflected more than men's. Sex differences of
      the crown sizes are specially defined on the second upper and second lower
      molars. In the result of the conducted researches, it was found and theoretically
      confirmed racial identity of Ternopil and Ternopil region citizens, and it was
      given the characteristics of the differences of odontometrical indices of molar
      crowns of males and females. The lore of these characteristics plays a great role
      in the clinic of prosthetic dentistry.

PMID- 29201442
TI  - Is there an association between ABO blood grouping and periodontal disease? A
      literature review.
AB  - Introduction: Although several studies have investigated the relationship between
      ABO blood group and medical diseases, few reports have explored the association
      with oral diseases, including periodontal disease (PD). Aim: The aim of this
      literature review was to assess the association between the ABO blood grouping
      and PD. Methods: We searched PubMed and Google Scholar databases using the
      following terms in different combinations: "ABO blood group," "periodontitis,"
      "aggressive periodontitis (AP)," "risk factor," and "Rhesus factor." Databases
      were searched for articles published from 1977 to August 2016. Titles and
      abstracts of articles were screened for English-language papers describing
      clinical studies, case reports, or retrospective studies of oral health status in
      patients with different ABO blood groups. Letters to the editor, historic
      reviews, and articles including unpublished data were excluded. Reference lists
      of included studies were reviewed for additional original and review studies.
      Results: We identified eight articles describing studies of the relationship
      between ABO blood groups and PD. The findings suggested a possible genetic basis
      in the association of the blood group AB with AP. Four studies showed that
      chronic periodontitis was more common among patients with blood group O.
      Conclusion: ABO blood subgroup and Rhesus factor could constitute risk predictors
      in the development of PD.

PMID- 29201445
TI  - The importance of knowledge: what's new in neuroendocrine thoracic tumors.

PMID- 29201443
TI  - Anatomical and morphological aspects of papillae, epithelium, muscles, and glands
      of rats' tongue: Light, scanning, and transmission electron microscopic study.
AB  - Purpose: The purpose of this paper is to describe the research results of the
      morphological structure of white laboratory rats' tongue at the macro-, micro-,
      and ultrastructural levels by scanning, light, and transmission electron
      microscopy. Results: Our results show that the tongue of these rats has a number
      of unique morphological features that are different from the tongue of other
      rodents consequently to allow identifying their species-specific features.
      Conclusions: Our findings have shown the features of the tongue structure of
      white laboratory rats at micro-, macro-, and ultrascopic levels. The data
      analysis revealed that mucous membrane of the tongue contains a large number of
      papillae, such as fungiform, filiform, foliate, vallate, and multifilamentary
      papillae. Each has a different shape, size, and location. The tongue's
      morphological feature consists of three types of filiform papillae, well
      developed foliate and multifilamentary papillae, as well as one large and similar
      smaller circumvallate papillae. The muscle of the tongue contains a large number
      of mitochondria of different shapes and sizes. However, we have received data for
      a complete picture of structure of this organ that will be useful in further
      experimental and morphological studies of the white laboratory rats.

PMID- 29201444
TI  - The interaction effects of resistance training and sustanon abuse on liver
      antioxidant activities and serum enzymes in male rats.
AB  - Background: Anabolic-androgenic steroids (AAS) are synthetic drugs derived from
      testosterone, the uncontrolled usage of which may lead to serious side effects.
      Previous studies have shown that resistance training (RT) is the main exercise
      modality practiced by AAS abusers. Thus, this work was carried out to evaluate
      the hepatotoxic effects of sustanon (Su) as an example of AAS in trained male
      rats. Methods: Rats were divided into sedentary/non-Su, sedentary/Su, RT/non-Su,
      and RT/Su. Su-administration groups received Su 10 mg/kg intramuscularly once a
      week for 8 weeks. In the 8-week RT, the rats climbed a vertical ladder 3
      days/week. Results: After Su administration, the mean values of serum parameters
      related to hepatic function were within normal ranges. Superoxide dismutase,
      glutathione peroxidase, and glutathione reductase activities were higher (P <
      0.05) in the liver of Su-treated rats. Chronic exercise alone did not change any
      of the above parameters. Conclusions: The present findings suggest that the 8
      week injection of Su, either with or without concurrent RT upregulation of
      enzymatic antioxidant activities and RT, did not attenuate the increase of
      enzymatic activities due to the Su administration. Furthermore, Su abuse in this
      dose did not make any severe liver damage.

PMID- 29201446
TI  - Surgical treatment of low and intermediate grade lung net.
AB  - Background: Carcinoids now constitute complex tumours which require a
      multidisciplinary approach and long-term follow-up. Surgical intervention is
      nowadays confirmed as the mainstay of treatment. Methods: From 1980 to 2015,
      EMETNE-SEPAR collected 1,339 patients treated surgically for bronchial carcinoid
      (1,154 typical and 185 atypical carcinoids). Standard and conservative procedures
      were considered with regard to surgical approach. All the patients with carcinoid
      were pathologically coded following the standards of the 7th edition 2009 TNM
      lung cancer staging. Statistical analyses were performed in order to determine
      whether histology, nodal affectation and surgical technique were associated with
      significant differences in survival, presence of metastases and local recurrence.
      Results: The influence of the surgical procedure on overall survival, the
      presence of metastases and local recurrence were demonstrated as no significant
      in our sample in central tumours (P>0.05). Sublobar resections in peripheral
      tumours are related to a decrease in survival in typical carcinoids (P=0.008)
      with nodal involvement and an increased number of recurrences in atypical
      carcinoids without nodal involvement (P=0.018). Conclusions: In central typical
      carcinoid, the use of lung-sparing bronchoplastic techniques could influence
      local recurrence in some cases. This observation demands the intraoperative
      pathologic verification of an adequate surgical margin by frozen section.
      Peripheral typical carcinoids have been surgically treated, occasionally, by
      sublobar resection. However, in peripheral atypical carcinoid after a limited
      sublobar resection the observed increase of the probability of local recurrence
      makes it, in our opinion, not advisable.

PMID- 29201447
TI  - Lung neuroendocrine tumors: pathological characteristics.
AB  - Lung neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms
      comprising four histologic types, namely typical and atypical carcinoid (TC and
      AC), large-cell neuroendocrine and small cell carcinoma (SCC). Classification
      criteria include the number of mitoses per 2 mm2, the occurrence and extent of
      necrosis, cytological and histological features and immunohistochemistry for
      neuroendocrine markers. The classification system and the diagnostic workflow of
      lung NETs are apparently easy to apply and well established. However, several
      unresolved issues still exist in classification and pathological characterization
      of these tumors, probably because inter-observer diagnostic reproducibility
      remains disappointing, likely due to inconsistency in recognizing necrosis,
      mitoses and cytological details, especially in small biopsy or cytological
      materials. Furthermore, the lack of strong prognostic and grading criteria leads
      to the incomplete interpretation of some rare intermediate entities that stand in
      between AC and large cell neuroendocrine carcinoma (LCNEC) categories.

PMID- 29201448
TI  - Neuroendocrine tumors of the thymus and mediastinum.
AB  - Neuroendocrine tumors of the thymus (tNET) and mediastinum are very rare
      neoplasms with scarce available data. All subtypes [typical and atypical
      carcinoid tumors (TC and AC), large cell neuroendocrine and small cell carcinoma
      (SCC)] observed elsewhere in the body occur also in the mediastinum and show only
      few if any organ-specific morphological differences. Although all available data
      suggest that the broad principles that govern the biology (and hence) the
      classification of these tumors in general apply also to tNET, there are a few
      noteworthy peculiarities related e.g., to risk factors, relative frequency and
      also to molecular genetic features. In this review, we will briefly summarize
      current knowledge on tNET with a special emphasis on shared and private features
      in comparison e.g., with pulmonary NET, which have traditionally been regarded
      the next closely related NET group.

PMID- 29201450
TI  - The role of surgery in high grade neuroendocrine tumours of the lung.
AB  - High grade lung neuroendocrine tumours are a heterogeneous subtype of pulmonary
      cancers including small cell lung cancer (SCLC) and large-cell neuroendocrine
      carcinoma (LCNEC). LCNEC represents approximately 2-3% of lung cancers, whereas
      SCLC represents 15-20% of lung cancers. Patients with SCLC and LCNEC have a poor
      prognosis compared with patients with non-small cell lung cancer (NSCLC). LCNEC
      is treated with primary surgical resection in stages I-II, which is similar to
      other NSCLCs. Neo-adjuvant treatment in stage III is similar to NSCLC but has not
      been well studied. LCNEC tumours have an unfavourable prognosis in higher stages
      but a more favourable prognosis in earlier stages. Surgery plays a minor role in
      treatment of SCLC because tumours are often locally advanced or have metastasized
      at the time of presentation and treatment relies on chemo- or chemoradiotherapy.
      However, patients with limited cancer may demonstrate better disease control upon
      surgical treatment. The resection rate of limited disease (LD) SCLC is low (1
      6%), but 5-year survival rates of 31-42% after surgical resection are encouraging
      and are significantly higher than the survival rates of comparable patients that
      did not have surgery. Curing SCLC in stage I is reported in up to 66% of cases.
      Local treatment with either resection or radiotherapy alone is followed by high
      rates of locoregional and distant recurrences, so preoperative or adjuvant
      treatment is recommended. Here, we summarise the similarities and differences of
      SCLC and LCNEC and highlight the role of surgery in the treatment of SCLC and
      LCNEC and its effect on local recurrence prevention.

PMID- 29201449
TI  - Molecular strategies in the management of bronchopulmonary and thymic
      neuroendocrine neoplasms.
AB  - Thoracic NETs [bronchopulmonary NETs (BPNETs) and thymic NETs (TNET)] share a
      common anatomic primary location, likely a common cell of origin, the "Kulchitsky
      cell" and presumably, a common etiopathogenesis. Although they are similarly
      grouped into well-differentiated [typical carcinoids (TC) and atypical carcinoids
      (AC)] and poorly differentiated neoplasms and both express somatostatin
      receptors, they exhibit a wide variation in clinical behavior. TNETs are more
      aggressive, are frequently metastatic, and have a lower 5-year survival rate
      (~50% vs. ~80%) than BPNETs. They are typically symptomatic, most often secreting
      ACTH (40% of tumors) but both tumor groups share secretion of common biomarkers
      including chromogranin A and 5-HIAA. Consistently effective and accurate
      circulating biomarkers are, however, currently unavailable. Surgery is the
      primary therapeutic tool for both BPNET and TNETs but there remains little
      consensus about later interventions e.g., targeted therapy, or how these can be
      monitored. Genetic analyses have identified different topographies (e.g.,
      significant alterations in chromatin and epigenetic remodeling in BPNETs versus
      frequent chromosomal abnormalities in TNETs) but there is an absence of
      clinically actionable mutations in both tumor groups. Liquid biopsies, tools that
      can measure neoplastic signatures in peripheral blood, can potentially be
      leveraged to detect disease early i.e., recurrence, predict tumors that may
      respond to specific therapies and serve as real-time monitors for treatment
      responses. Recent studies have identified that mRNA transcript analysis in blood
      effectively identifies both BPNET and TNETs. The clinical utility of this gene
      expression assay includes use as a diagnostic, confirmation of completeness of
      surgical resection and use as a molecular management tool to monitor efficacy of
      PRRT and other therapeutic strategies.

PMID- 29201451
TI  - Neuroendocrine tumors of the thymus.
AB  - Primary neuroendocrine tumors of the thymus (NETTs) are rare and biologically
      very aggressive neoplasms, usually located in the anterior mediastinal space.
      They are more frequently observed in males, in their fourth/fifth decades of
      life. In 50% of cases, NETTs are associated with endocrinopaties [Cushing's
      syndrome, acromegaly or Multiple Endocrine Neoplasia-1 (MEN-1) syndrome]. NETTs
      very often present with invasion of the surrounding mediastinal anatomical
      structures. Surgery, even in advanced stages, is the mainstay of treatment: a
      compete resection through a median sternotomy or a combined access (sternotomy +
      thoracotomy) should be always attempted. Induction chemotherapy (+/-
      radiotherapy) is usually administered in advanced neoplasms, with the aim to
      achieve tumor shinkage, increasing, therefore, the chance to obtain a complete
      resection. Postoperative radiotherapy (+/- chemotherapy) is administered in case
      of invasive lesions, or incomplete resections. NETTs long-term outcome is poor,
      even in case of completely resected tumors, due to high risk of recurrence or
      distant metastases development. Prognosis mainly depends on tumor stage,
      invasivity, completeness of resection, possible association with endocrinopaties
      and recurrence/distant metastases development.

PMID- 29201452
TI  - Neuroendocrine tumors of the thymus: the oncologist point of view.
AB  - Thymic malignancies represent a heterogeneous group of rare thoracic cancers,
      which are classified according to the World Health Organization (WHO)
      histopathologic classification that distinguishes thymomas from thymic carcinomas
      and neuroendocrine tumors; neuroendocrine thymic tumors (NETTs) exhibit the same
      histological spectrum as in other anatomical locations, although with different
      frequencies. NETTs represent around 2% of all neuroendocrine tumors, and about 5%
      of all thymic malignancies. Overall, the management of patients with NETTs tumors
      requires continuous multidisciplinary expertise at any step of the disease
      progression. Systemic treatment relies on cytotoxic chemotherapy, as well as on
      somatostatin analogues and everolimus. Systemic treatment may be delivered in a
      curative-intent approach, for patients presenting with locally-advanced tumor at
      the time of diagnosis, with invasion of intra-thoracic neighboring structures. In
      such cases, chemotherapy has been used in an induction setting, to reduce the
      tumor burden-possibly allowing subsequent surgery and/or radiotherapy-or as a
      postoperative treatment if the tumor was resectable upfront, to reduce the risk
      of recurrence and achieve prolonged disease control. Systemic therapies are also
      a palliative-intent treatment of unresectable, metastatic, and recurrent NETTs.
      Chemotherapy may then be an option for aggressive disease, but somatostatin
      analogues and everolimus are suitable as well. Alternative options are emerging
      through clinical trials. As no dedicated study has ever been conducted,
      recommendations for systemic treatment in NETTs have been mostly based on
      retrospective cohorts of limited numbers patients, especially in the advanced
      disease setting, and expert opinion based on experience from primary pulmonary,
      as well as gastro-intestinal neuroendocrine tumors, for which clinical trials
      have been conducted.

PMID- 29201453
TI  - The role of multimodal treatment in patients with advanced lung neuroendocrine
      tumors.
AB  - Lung neuroendocrine tumors (NETs) comprise typical (TC) and atypical carcinoids
      (AC). They represent the well differentiated (WD) or low/intermediate grade forms
      of lung neuroendocrine neoplasms (NENs). Unlike the lung poorly differentiated
      NENs, that are usually treated with chemotherapy, lung NETs can be managed with
      several different therapies, making a multidisciplinary interaction a key point.
      We critically discussed the multimodal clinical management of patients with
      advanced lung NETs. Provided that no therapeutic algorithm has been validate so
      far, each clinical case should be discussed within a NEN-dedicated
      multidisciplinary team. Among the systemic therapies available for metastatic
      lung NETs everolimus is the only approved drug, on the basis of the results of
      the phase III RADIANT-4 trial. Another phase III trial, the SPINET, is ongoing
      comparing lanreotide with placebo. Peptide receptor radionuclide therapy and
      chemotherapy were not studied within phase III trials for lung NETs, and they
      have been reported to be active within retrospective or phase II prospective
      studies. Temozolomide and oxaliplatin are two interesting chemotherapeutic agents
      in lung NETs. While some European Institutions were certificated as Centers of
      Excellence for gastroenteropancreatic NENs by the European Neuroendocrine Tumor
      Society (ENETS), an equivalent ENETS certification for lung NENs does not exist
      yet. Ideally a lung NEN-dedicated multidisciplinary tumor board should include
      NEN-dedicated medical oncologists, thoracic medical oncologist, thoracic
      surgeons, pathologists, interventional radiologists, endocrinologists,
      radiotherapists, interventional pneumologists, nuclear physician.

PMID- 29201454
TI  - The role of peptide receptor radionuclide therapy in advanced/metastatic thoracic
      neuroendocrine tumors.
AB  - Bronchopulmonary (BP) neuroendocrine tumors (NETs) comprise a spectrum of tumors
      that develop from respiratory neuroendocrine cells and represent ~20% of all lung
      neoplasia and ~30% of all NETs. The only curative treatment is surgical
      resection. For well-differentiated forms (typical and atypical carcinoids),
      medical therapy ranges from bioactive agents (e.g., somatostatin analogs), to
      biotherapy (e.g., everolimus), standard chemotherapy and peptide receptor
      radionuclide therapy (PRRT). PRRT with radiolabeled somatostatin analogs is an
      innovative treatment for inoperable or metastasized, well/moderately
      differentiated, NET. Initially developed for gastroenteropancreatic tumors, it is
      also used in BP-NET because these tumors express the target receptor. Two decades
      of clinical trials with either 90Y-octreotide or 177Lu-octreotate, have
      demonstrated the efficacy of PRRT, as measured by tumor response, symptom relief
      and quality of life (QoL) improvement. PRRT with 90Y- and 177Lu-peptides is
      generally well-tolerated and adverse events (kidney and bone marrow) are modest.
      The paper illustrates the history, technique and results of this treatment in the
      few dedicated studies and the many BP NET cases embedded within larger NET
      series. The limitations of the present body of information are addressed, and the
      future perspectives, in terms of prospective studies required to define the
      position of PRRT in the therapeutic algorithm of BP-NETs and the need for
      predictive molecular biomarkers to guide future studies, are discussed.

PMID- 29201455
TI  - Optofluidic Lab-on-a-Chip Fluorescence Sensor Using Integrated Buried ARROW
      (bARROW) Waveguides.
AB  - Optofluidic, lab-on-a-chip fluorescence sensors were fabricated using buried anti
      resonant reflecting optical waveguides (bARROWs). The bARROWs are impervious to
      the negative water absorption effects that typically occur in waveguides made
      using hygroscopic, plasma-enhanced chemical vapor deposition (PECVD) oxides.
      These sensors were used to detect fluorescent microbeads and had an average
      signal-to-noise ratio (SNR) that was 81.3% higher than that of single-oxide ARROW
      fluorescence sensors. While the single-oxide ARROW sensors were annealed at 300 
      degrees C to drive moisture out of the waveguides, the bARROW sensors required no
      annealing process to obtain a high SNR.

PMID- 29201456
TI  - Use of OCT Angiography in Choroidal Melanocytic Tumors.
AB  - Objective: To describe OCTA findings in choroidal melanocytic tumors, especially
      the microcirculation patterns, and to try to correlate with the histopathological
      studies. Methods: Cross-sectional, comparative, observational study. 70 cases,
      including 55 choroidal nevi and 15 choroidal melanomas. Three different observers
      evaluated specific variables in the choriocapillaris layer on AOCT images and
      searched for images which described histopathologic vascular patterns, and also,
      a general description of the images was made. Complementary multi-imaging studies
      included EDI SD-OCT, color and autofluorescence fundus imaging, Doppler
      ultrasound, and indocyanine/fluorescein angiography. Main Results: Good quality
      studies were acquired in 80% of the cases, with kappa indexes 0.768-0.958. Nevus
      OCTA images were described mainly as hyperreflective (72.7%), whereas choroidal
      melanoma as iso/hyporeflective (62.5%). Avascular areas were found in 50.96% and
      in 33.3% of choroidal nevus and choroidal melanomas, respectively. A neovascular
      membrane was found only in cases of choroidal nevus (16.3%). Only in cases of
      choroidal melanomas, we found vascular loops (6.6%) or vascular networks (6.6%).
      Conclusion: OCTA is a promising new technology that can be used to study in vivo
      the differential characteristics of microcirculations between posterior segment
      melanocytic lesions. Today, larger studies are needed to corroborate these
      findings and to correlate it with malignancy.

PMID- 29201457
TI  - The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal
      Neovascularization in Rats.
AB  - The aims of this study were to evaluate the effects of CM082 on the development
      of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to
      determine the drug concentration in the ocular tissues. After the laser-induced
      CNV model was established in rats, CM082 was orally administered. The effects of
      CM082 on the CNV lesions were assessed using fundus fluorescein angiography
      (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera
      eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were
      determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated
      that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly
      less neovascularization than did the control group. The total concentration of
      CM082 in the eyes (172.86 +/- 57.11 ng/g) was similar to that in the plasma
      (196.87 +/- 73.13 ng/ml). Within the eye, the concentrations of CM082 and its
      metabolites were highest in the retina-sclera. The orally administered CM082 thus
      effectively passed through the blood-retina barrier (BRB) to reach the retina in
      the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was
      able to reduce CNV lesions in the laser-induced CNV rat model.

PMID- 29201458
TI  - Switch to Aflibercept in the Treatment of Neovascular AMD: Long-Term Results.
AB  - Purpose: To report the long-term clinical outcomes after switching from
      intravitreal bevacizumab or ranibizumab to aflibercept therapy in eyes with AMD.
      Methods: Retrospective analysis of changes in BCVA, SD-OCT image, and frequency
      of injections after 1, 2, and 3 years of follow-up. Results: 164 eyes were
      analyzed, 101 eyes switched from bevacizumab (group 1) and 63 from ranibizumab
      (group 2). One year after the switch, there was an overall nonsignificant mean
      decrease of 2 ETDRS letters in BCVA. Three years after, there was an overall mean
      decrease of 7 ETDRS letters, which was statistically significant. A significant
      improvement in the mean CRT was found at 1, 2, and 3 years. There was a
      significant decrease in the mean number of injections per year (7.8 to 6.5, p <
      0.005) between the first and third year. Conclusion: Aflibercept can be useful in
      the management of refractory neovascular AMD, with a good morphological response.
      However, in the long-term, BCVA stabilization was not achieved.

PMID- 29201459
TI  - Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal
      Power in Keratoconus Eyes after Accelerated Corneal Collagen Crosslinking.
AB  - Purpose: To analyze the errors associated to corneal power calculation using the
      keratometric approach in keratoconus eyes after accelerated corneal collagen
      crosslinking (CXL) surgery and to obtain a model for the estimation of an
      adjusted corneal refractive index (nkadj ) minimizing such errors. Methods:
      Potential differences (DeltaPc) among keratometric (Pk ) and Gaussian corneal
      power (PcGauss) were simulated. Three algorithms based on the use of nkadj for
      the estimation of an adjusted keratometric corneal power (Pkadj ) were developed.
      The agreement between Pk(1.3375) (keratometric power using the keratometric index
      of 1.3375), PcGauss, and Pkadj was evaluated. The validity of the algorithm
      developed was investigated in 21 keratoconus eyes undergoing accelerated CXL.
      Results: Pk(1.3375) overestimated corneal power between 0.3 and 3.2 D in
      theoretical simulations and between 0.8 and 2.9 D in the clinical study
      (DeltaPc). Three linear equations were defined for nkadj to be used for different
      ranges of r1c. In the clinical study, differences between Pkadj and PcGauss did
      not exceed +/-0.8 D nk = 1.3375. No statistically significant differences were
      found between Pkadj and PcGauss (p > 0.05) and Pk(1.3375) and Pkadj (p < 0.001).
      Conclusions: The use of the keratometric approach in keratoconus eyes after
      accelerated CXL can lead to significant clinical errors. These errors can be
      minimized with an adjusted keratometric approach.

PMID- 29201460
TI  - Early Diagnosis of HIV among Infants Born to HIV-Positive Mothers on Option-B
      Plus in Kampala, Uganda.
AB  - Introduction: Globally, there is delay in accessing early HIV diagnosis (EID)
      among HIV exposed infants (HEIs). With paucity of data on EID use at Kisenyi
      Health Center, this study assessed factors associated with EID use among HEIs
      (HIV exposed infants). Method: This was a cross-sectional study of 246 HIV
      positive mother-baby pairs. Data was collected by structured questionnaire,
      double-entered in EpiData, and analyzed with STATA using multinomial logistic
      regression at 5% significance level. Results: 132 (53.7%) HEIs were not tested,
      60 (24.4%) tested outside EID guideline, and 54 (21.9%) tested per the guideline.
      Testing per guideline was associated with maternal age above 30 years (AOR =
      2.75; 95% CI: 1.20-6.34; P = 0.017); testing outside the guideline was associated
      with maternal HIV serostatus disclosure (AOR = 2.70; 95% CI: 1.10-6.63; P =
      0.003) and four or more antenatal care (ANC) visits (AOR = 3.25; 95% CI: 1.23
      8.59; P = 0.017). However, maternal knowledge of HIV transmission was associated
      with testing outside the guideline (AOR = 2.90; 95% CI: 1.10-7.65; P = 0.032) and
      per the guideline (AOR = 3.70; 95% CI: 1.39-9.88; P = 0.009). Conclusion: Timely
      EID testing was low. Improving maternal knowledge of EID during ANC visits and
      positive living empowerment is critical.

PMID- 29201461
TI  - Fluorinated Adenosine A2A Receptor Antagonists Inspired by Preladenant as
      Potential Cancer Immunotherapeutics.
AB  - Antagonism of the adenosine A2A receptor on T cells blocks the hypoxia
      adenosinergic pathway to promote tumor rejection. Using an in vivo immunoassay
      based on the Concanavalin A mouse model, a series of A2A antagonists were studied
      and identified preladenant as a potent lead compound for development. Molecular
      modeling was employed to assist drug design and subsequent synthesis of analogs
      and those of tozadenant, including fluorinated polyethylene glycol PEGylated
      derivatives. The efficacy of the analogs was evaluated using two in vitro
      functional bioassays, and compound 29, a fluorinated triethylene glycol
      derivative of preladenant, was confirmed as a potential immunotherapeutic agent.

PMID- 29201462
TI  - Efficacy of Second-Line Pemetrexed-Carboplatin in EGFR-Activating Mutation
      Positive NSCLC: Does Exon 19 Deletion Differ from Exon 21 Mutation?
AB  - Background: It is unknown whether the outcomes of second-line pemetrexed
      carboplatin chemotherapy administered after progression on gefitinib are
      dependent on type of EGFR mutation present at baseline. Method: Adult non-small
      cell lung cancer patients, with exon 19 deletion or exon 21 L858R mutation, who
      progressed on gefitinib and received pemetrexed-carboplatin chemotherapy were
      selected for this analysis. Result: 55 patients received pemetrexed-carboplatin
      as second-line treatment. Response rates in evaluable patients were 39.3% in exon
      19 patients (n = 28) and 33.3% in exon 21 patients (n = 15) (p = 0.752, Fisher's
      exact 2-sided p value). The median PFS in exon 19 and 21 cohorts was 5.900 months
      (95% CI: 4.274-7.526) and 4.767 months (95% CI: 1.374-8.159), respectively. The
      median overall survival in exon 19 patients was (11.8 months, 95% CI: 9.916
      13.684 months) significantly better than that seen in exon 21 mutation patients
      (6.2 months, 95% CI: 4.215-8.118 months, p = 0.024) on univariate analysis;
      however, on multivariate analysis, this association was not confirmed (HR =
      0.361, 95% CI: 0.090-1.439, p = 0.149). Conclusion: Exon 19 deletion has no
      impact on PFS and OS in EGFR-mutated patients treated with second-line pemetrexed
      carboplatin.

PMID- 29201463
TI  - Complex Monitoring of Biochemical and Radionuclide Parameters in Patients with
      Metastatic Renal Cell Carcinoma during Immunotherapy.
AB  - Study Objective: To study the effectiveness of complex monitoring of the kidney
      function, based on biochemical and radionuclide methods in patients with
      metastatic renal cell carcinoma (mRCC). Materials and Methods: 41 mRCC patients
      after nephrectomy received nivolumab (n = 23) and interferon-alpha (n = 18) from
      2015 to 2017. At baseline and 2 months after, all patients underwent blood
      chemistry, urinalysis, Rehberg test, and ELISA to determine serum levels of IL
      17A, TGF-beta, and erythropoietin. The monitoring of the renal function and
      urodynamics by complex renal scintigraphy (CRS) was used for all patients using a
      dual-detector gamma camera and simultaneous data recording in 2 projections. The
      interpretation of CRS data used the original SENS CRS technology. Study Results:
      Statistically significant correlations were established between IL-17A, TGF-beta,
      and D (excretion rate of 99mTc-technephore from the parenchyma) and Rnfsc (a
      stable sign of nephrosclerosis), respectively. A significant correlation was
      established between the parameters of the complex functional monitoring with the
      prognosis for the risk of renal failure (RF) and efficacy of immunotherapy in
      mRCC. Conclusions: All mRCC patients after nephrectomy were recommended to
      undergo biochemical monitoring with inclusion of TGF-beta and IL-17A, as well as
      radionuclide monitoring (CRS) to determine the RF risk at an early stage.

PMID- 29201464
TI  - Health Indicators of US Older Adults Who Received or Did Not Receive Meals Funded
      by the Older Americans Act.
AB  - Background: The Older Americans Act (OAA) requires that nutrition programs
      provide meals and related nutrition services that promote health and help manage
      chronic diseases. The purpose of this study was to compare health status, food
      security, functional limitations, and chronic diseases of older adults who
      received or did not receive OAA meals using data from a representative sample of
      US adults. Methods: Data were from the National Health and Nutrition Surveys 2011
      2014 for 2,392 older adults >= 65 years of age, including 187 Mexican Americans,
      212 other Hispanics, 521 non-Hispanic Blacks, 219 non-Hispanic Asians, and 1253
      non-Hispanic Whites. Results: Those receiving OAA meals had higher percent of
      food insecurity and functional disabilities. Adjusting for potential confounders,
      adults who received OAA meals had higher odds of emphysema (OR = 2.02; 1.05,
      3.89) and lower odds of good-to-excellent health (OR = 0.52; 0.36, 0.77). Women
      and minorities had poorer health status compared to non-Hispanic Whites.
      Conclusion: A higher proportion of older adults who received nutritional services
      reported poorer health as compared to older adults who do not participate in
      these services. Future studies should assess nutritional adequacy for older
      adults who participate in nutritional programs comparing sex and race/ethnicity.

PMID- 29201465
TI  - A Reliable and Reproducible Model for Assessing the Effect of Different
      Concentrations of alpha-Solanine on Rat Bone Marrow Mesenchymal Stem Cells.
AB  - Alphalpha-solanine (alpha-solanine) is a glycoalkaloid present in potato (Solanum
      tuberosum). It has been of particular interest because of its toxicity and
      potential teratogenic effects that include abnormalities of the central nervous
      system, such as exencephaly, encephalocele, and anophthalmia. Various types of
      cell culture have been used as experimental models to determine the effect of
      alpha-solanine on cell physiology. The morphological changes in the mesenchymal
      stem cell upon exposure to alpha-solanine have not been established. This study
      aimed to describe a reliable and reproducible model for assessing the structural
      changes induced by exposure of mouse bone marrow mesenchymal stem cells (MSCs) to
      different concentrations of alpha-solanine for 24 h. The results demonstrate that
      nonlethal concentrations of alpha-solanine (2-6 MUM) changed the morphology of
      the cells, including an increase in the number of nucleoli, suggesting elevated
      protein synthesis, and the formation of spicules. In addition, treatment with
      alpha-solanine reduced the number of adherent cells and the formation of colonies
      in culture. Immunophenotypic characterization and staining of MSCs are proposed
      as a reproducible method that allows description of cells exposed to the
      glycoalkaloid, alpha-solanine.

PMID- 29201466
TI  - Breast Cancer Status in Iran: Statistical Analysis of 3010 Cases between 1998 and
      2014.
AB  - Background: Breast cancer is the 5th leading cause of cancer death in Iranian
      women. This study analyzed 3010 women with breast cancer that had been referred
      to a cancer research center in Tehran between 1998 and 2014. Methods: In this
      retrospective study, we analyzed 3010 breast cancer cases with 32 clinical and
      paraclinical attributes. We checked the data quality rigorously and removed any
      invalid values or records. The method was data mining (problem definition, data
      preparation, data exploration, modeling, evaluation, and deployment). However,
      only the descriptive analyses' results of the variables are presented in this
      article. To our knowledge, this is the most comprehensive study on breast cancer
      status in Iran. Results: A typical Iranian breast cancer patient has been a 40-50
      year-old married woman with two children, who has a high school diploma and no
      history of abortion, smoking, or diabetes. Most patients were estrogen and
      progesterone receptor positive, human epidermal growth factor (HER) negative, and
      P53 negative. Most cases were detected in stage 2 with intermediate grade.
      Conclusion: This study revealed original findings which can be used in national
      policymaking to find the best early detection method and improve the care quality
      and breast cancer prevention in Iran.

PMID- 29201467
TI  - Constitutive Expression of Adiponectin in Endothelial Progenitor Cells Protects a
      Rat Model of Cerebral Ischemia.
AB  - Endothelial progenitor cells (EPCs), as precursors to endothelial cells, play a
      significant part in the process of endogenous blood vessel repair and maintenance
      of endothelial integrity. Adiponectin (APN) is an adipocyte-specific
      adipocytokine. In this study, we aim to test whether we transplant a combined
      graft of EPCs transfected with the adiponectin gene into a rat model of cerebral
      ischemia could improve functional recovery after middle cerebral artery occlusion
      (MCAO). Sprague-Dawley (SD) rats were randomly divided into a MCAO control group,
      a MCAO EPC treatment group, and a MCAO LV-APN-EPC treatment group. A focal
      cerebral ischemia and reperfusion model was induced by the intraluminal suture
      method. After 2 h of reperfusion, EPCs were transplanted by injection through the
      tail vein. A rotarod test was conducted to assess behavioral function before MCAO
      and on days 1, 7, and 14 after MCAO. After 14 d, TTC staining, CD31
      immunofluorescence, and TUNEL staining were used to evaluate infarct volume,
      microvessel density, and cell apoptosis. Results revealed that behavioral
      function, infarct area percentage, microvessel density, and cell apoptosis rates
      were more favorable in the LV-APN-EPC treatment group than in the EPC treatment
      group. These data suggested that gene-modified cell therapy may be a useful
      approach for the treatment of ischemic stroke.

PMID- 29201468
TI  - A Case Report of Recurrent Takotsubo Cardiomyopathy in a Patient during
      Myasthenia Crisis.
AB  - Introduction: Patients with myasthenia crisis can develop Takotsubo stress
      cardiomyopathy (SC) due to emotional or physical stress and high level of
      circulating catecholamines. We report a patient who developed recurrent Takotsubo
      cardiomyopathy during myasthenia crisis. Coexisting autoimmune disorders known to
      precipitate stress cardiomyopathy like Grave's disease need to be evaluated. Case
      Report: A 69-year-old female with seropositive myasthenia gravis (MG), Grave's
      disease, and coronary artery disease on monthly infusion of intravenous
      immunoglobulin (IVIG), prednisone, pyridostigmine, and methimazole presented with
      shortness of breath and chest pain. Electrocardiogram (ECG) showed ST elevation
      in anterolateral leads with troponemia. Coronary angiogram was unremarkable for
      occlusive coronary disease with left ventriculogram showing reduced wall motion
      with apical and mid left ventricle (LV) hypokinesis suggestive of Takotsubo
      stress cardiomyopathy. Her symptoms were attributed to MG crisis. Her symptoms,
      ECG, and echocardiographic findings resolved after five cycles of plasma exchange
      (PLEX). She had another similar episode one year later during myasthenia crisis
      with subsequent resolution in 10 days after PLEX. Conclusion: Takotsubo
      cardiomyopathy can be one of the manifestations of myasthenia crisis with or
      without coexisting Grave's disease. These patients might benefit from meticulous
      fluid status and cardiac monitoring while administering rescue treatments like
      IVIG and PLEX.

PMID- 29201469
TI  - Perforated Duodenal Diverticulum with Subtle Pneumoretroperitoneum on Abdominal X
      Ray.
AB  - Abdominal pain is one of the most common presenting complaints at the Emergency
      Department (ED). Given the myriad of possible differential diagnoses for
      abdominal pain, it becomes more important to diagnose conditions requiring
      emergent surgical intervention early. We present a case of an elderly male
      patient with abdominal pain secondary to perforated hollow viscus, subtle
      evidence of pneumoretroperitoneum on the initial supine abdominal X-ray, and
      review the signs of pneumoperitoneum and pneumoretroperitoneum on plain abdominal
      X-rays.

PMID- 29201470
TI  - A Novel Mutation of the CYP11B2 in a Saudi Infant with Primary Hypoaldosteronism.
AB  - Isolated hypoaldosteronism is a rare autosomal recessive disease presenting with
      severe salt wasting and failure to thrive in infancy. A 6-month-old Saudi girl
      born to consanguineous parents was referred from primary health care for failure
      to thrive and developmental delay. Laboratory tests revealed hyponatremia,
      hyperkalemia, and metabolic acidosis with high renin and low aldosterone. Blood
      samples were collected for endocrine and genetic studies. Sequence analysis of
      the CYP11B2 revealed a T to A transition at position 1398 + 2 in exon 8 of the
      gene in a homozygous state (c.1398+T>A). This result was confirmed by sequencing
      an independent PCR product. Given the position of the transition at a highly
      conserved nucleotide and the predictions of different bioinformatic algorithms,
      it is likely that the mutation is the pathogenic cause of this condition. This
      result was compared with the reference NM_000498.3. Here, we report a novel
      homozygous mutation resulting in aldosterone synthase deficiency. To the best of
      our knowledge, this mutation has not been described in the literature or in any
      database thus far. The mutation manifested as a rare inherited disease in an
      infant exhibiting critical salt loss. An adequate replacement treatment will give
      a good long-term prognosis.

PMID- 29201471
TI  - Metastatic Renal Cell Cancer to Thyroid Diagnosed by Endoscopic Ultrasound Guided
      Fine Needle Aspiration Technique.
AB  - Medical literature about the role of endoscopic ultrasound (EUS) in identifying
      thyroid lesions is limited. We present a case of secondary thyroid cancer from
      renal cell carcinoma (RCC) metastasis, diagnosed by thyroid EUS-fine needle
      aspiration (FNA) approach that was done for staging of esophageal adenocarcinoma,
      in a patient with 11-year history of complete right nephrectomy for RCC. An 81
      year-old female patient underwent EUS for the evaluation of a newly discovered
      distal esophageal cancer. A hypoechoic, round, and well-demarcated mass that
      measured 26.9 mm * 21.9 mm was noticed in the right lobe thyroid gland. Therefore
      FNA was performed. The cytological results were consistent with metastatic RCC.
      In conclusion, EUS-FNA of thyroid nodule is a feasible and safe technique that
      can be used to evaluate any suspicious thyroid nodule. This case emphasizes the
      importance of carefully examining the thyroid gland during routine upper
      esophageal EUS examinations in the presence of history of nonthyroidal cancer.

PMID- 29201472
TI  - Severe Cytomegalovirus Reactivation in Patient with Low-Grade Non-Hodgkin's
      Lymphoma after Standard Chemotherapy.
AB  - Clinically significant cytomegalovirus (CMV) reactivation is not uncommon in
      patients with severe immunodeficiency secondary to underlying medical disorders
      or following aggressive immunosuppressive therapy. However, it is less frequently
      found in patients with low-grade haematological malignancies after nonintensive
      chemotherapy. We treated a patient at our centre for stage IVB follicular
      lymphoma with standard chemotherapy who successively developed CMV colitis
      associated with a CMV viral load of >3 million copies/ml. Four lines of antiviral
      treatment were necessary to obtain biochemical remission with undetectable CMV
      levels, with an initially insufficient response to valganciclovir despite
      therapeutic pre- and posttreatment levels. Subsequently, our patient also
      developed an infection with Pneumocystis jirovecii pneumonia (PJP) as further
      evidence of severe immune compromise. This case report demonstrates the
      importance of including investigations for less common sources of infection when
      confronted with a patient with a low-grade haematological malignancy and a
      pyrexia of unknown origin.

PMID- 29201473
TI  - Recurrent Huge Left Bartholin's Gland Abscess for One Year in a Teenager.
AB  - Bartholin's gland abscess is the commonest worldwide reported abscess in
      gynaecological outpatient clinics; it has also been reported that Bartholin's
      gland abscess is three times more common in occurrences compared to Bartholin's
      gland cyst. It is more common in women who are at risk of acquiring sexually
      transmitted infections; however, other causes of infection should be investigated
      to exclude other causes of disease. We present the case of an 18-year-old female
      patient, a teenager of the reproductive age group, with the recurrent development
      of huge Bartholin's gland abscess in a period of one year. The marsupialization
      surgical technique of repair was performed successfully. She was discharged home
      and she was scheduled to visit STI's clinic where she was receiving regular
      screening for STI's and she was also given health education regarding preventive
      measures for STI's.

PMID- 29201474
TI  - Globus Pallidus Internus Deep Brain Stimulation for Disabling Diabetic
      Hemiballism/Hemichorea.
AB  - Unilateral hemichorea/hemiballism (HH) associated with contralateral neuroimaging
      abnormalities of the basal ganglia, which is characterized by T1 hyperintensity
      on magnetic resonance imaging (MRI) and is secondary to diabetic nonketotic
      hyperglycemia, is a rare and unique complication of poorly controlled diabetes
      mellitus (DM). Although almost all prior reports have documented rapid resolution
      of HH within days after normalization of blood glucose levels, medically
      refractory persistent HH has been noted. The experience of surgical intervention
      for persistent HH is limited. A 46-year-old, right-handed female patient with
      type 2 DM presented with refractory diabetic HH on the left side of 6 months'
      duration despite DM control and neuroleptic medication usage. Image-guided deep
      brain stimulation (DBS) on the right globus pallidus internus (GPi) was
      performed. A mechanical micropallidotomy effect was observed and chronic
      stimulation of GPi was quite effective in symptomatic control of diabetic HH
      until a 16-month follow-up visit. DBS of the GPi can be an effective treatment
      for medically refractory diabetic HH.

PMID- 29201475
TI  - A Rare Case of Glioblastoma Multiforme with Osseous Metastases.
AB  - Glioblastoma multiforme is the most common malignant primary central nervous
      system neoplasm in adults. It has a very aggressive natural history with a median
      overall survival estimated at 14.6 months despite multimodality treatment.
      Extracranial metastases are very rare with few case reports published to date. We
      report the case of a 65-year-old male who underwent maximal safe resection for a
      newly diagnosed brain mass after presentation with new neurologic symptoms. He
      then received standard postsurgical adjuvant treatment for glioblastoma.
      Subsequently, he underwent another resection for early progressive disease.
      Several months later, he was hospitalized for new-onset musculoskeletal
      complaints. Additional investigation revealed new metastatic osseous lesions
      which were initially felt to be a new malignancy. The patient opted for
      supportive care and died 12 days later. Despite choosing no treatment, he elected
      to undergo a bone biopsy to understand the new underlying process. Results were
      that of metastatic GBM and were reported after the patient expired. Physicians
      caring for patients with GBM and new nonneurologic symptoms may contemplate body
      imaging.

PMID- 29201476
TI  - Multimodal Imaging Analysis in a Case with Congenital Fovea-Involving Retinal
      Macrovessel and Excellent Visual Acuity.
AB  - Purpose: Congenital retinal macrovessels (CRM) represent rare aberrant
      vasculature of the retinal vessels that can supply or drain the macula. In this
      report, the optical coherence tomography angiography features of a congenital
      retinal macrovessel are discussed. Methods: The history and examination findings
      are presented alongside swept-source OCT angiography with corresponding B scan
      and en face OCT imaging. Patients: The case is a 12-year-old female patient with
      excellent best-corrected visual acuity in both eyes. Results: Swept-source OCT
      angiography demonstrated considerable loss of the foveal avascular zone at the
      levels of the superficial and deep capillary plexus. Discussion: In this case
      there was no detrimental effect on vision despite anatomical loss of the foveal
      avascular zone.

PMID- 29201477
TI  - A Case of Advanced Glaucoma with Increased Episcleral Venous Pressure in a 17
      Year-Old with Eisenmenger Syndrome.
AB  - Eisenmenger syndrome refers to reversal of shunt and central cyanosis due to
      pulmonary hypertension induced by congenital heart disease with a large systemic
      to-pulmonary shunt. We report a case of a 17-year-old man with Eisenmenger
      syndrome who presented with gradual deterioration in visual acuity and was
      diagnosed with advanced secondary open angle glaucoma. There have been reports of
      patients suffering from thrombosis due to hyperviscosity associated with this
      syndrome; however, to our knowledge, the association of secondary open angle
      glaucoma with Eisenmenger syndrome has not yet been documented.

PMID- 29201478
TI  - Historical Case of Cervical Penetrating Wound: From First Aid to Surgical
      Intervention.
AB  - Objective: We report a case of cervical penetrating wound by posing the problem
      of its support and by analyzing the chain of survival of a patient to human
      sacrifice. Case Report: It was an 11-year-old boy admitted to the hosting service
      of cervical penetrating wound emergency occurring in a context of human sacrifice
      by weapon (knife). On admission, the conscious patient had a left cervical
      hematoma at the level of the cervical zone II and severe signs of acute anemia.
      The exploratory cervicotomy, carried out 12 hours after the trauma under
      transfusion, allowed us to highlight a section of the front edge of the
      sternocleidomastoid and previous jugular muscles under hyoid. We noted the
      presence of a linear wound of 1 cm at the level of the left internal jugular
      vein. The wound of the internal jugular vein has been repaired with the Prolene
      4.O. The outcome was good, allowing the exit 10 days after cervicotomy.
      Conclusion: The causal circumstances of cervical penetrating wounds are diverse.
      Their importance or their severity depends on the causative circumstances
      dominated by aggression and attempts to autolysis. Human sacrifice, with use of
      the weapon, is an exceptional circumstance.

PMID- 29201479
TI  - Lingual Osseous Choristoma of the Tongue Base: Unusual Presentation of a Rare
      Entity.
AB  - Osseous lesions of the tongue, also referred to as osseous choristomas, are
      benign growths of bony tissue. These lesions are not true neoplasms but rather
      represent growth of normal tissue at an abnormal location. Clinically, they
      appear as exophytic masses of the tongue, and they are treated by surgical
      excision. Lingual osseous choristomas are rare entities, with only 71 reported
      cases in the literature. We present the case of a lingual osseous choristoma of
      the tongue base in a 21-year-old female. Of the cases of lingual osseous
      choristoma reported in the literature, ours is only the fifth case to involve
      this location.

PMID- 29201480
TI  - Cholesterol Granuloma in the Maxillary Sinus: Are Endodontically Treated Teeth
      Involved in Its Etiopathogenesis?
AB  - Cholesterol granuloma (CG) is a tissue reaction in response to the accumulation
      of cholesterol crystals rarely found in the maxillary sinus. The etiopathogenesis
      of maxillary sinus CG remains unclear. We reviewed the literature and added two
      new reports of cholesterol granuloma in maxillary sinus related to endodontically
      treated maxillary posterior teeth. The first report refers to a 45-year-old woman
      diagnosed with rhinitis, who was submitted to endodontic retreatment of maxillary
      molar, and subsequently showed maxillary sinus opacity with cystic appearance.
      The second case describes a young adult woman, who presented a cystic mass in
      maxillary sinus after endodontic treatment, in close association with the apex of
      the maxillary right second premolar. Both patients were treated by a classic
      Caldwell-Luc surgery and the microscopic analyses revealed maxillary sinus CG. In
      the following, the authors discuss the probable involvement of endodontically
      treated maxillary posterior teeth in the etiopathogenesis of maxillary sinus CG.

PMID- 29201481
TI  - Cystic Lymphangioma of the Chest Wall in a 5-Year-Old Male Patient: A Rare and
      Atypical Localization-A Case Report and Comprehensive Review of the Literature.
AB  - Lymphangioma is a benign congenital malformation. The extremely rare and atypical
      localization of a lymphangioma in the chest wall was the real motive for the
      present case study. A 5-year-old boy was admitted to the Emergency Department of
      the 1st Department of Pediatric Surgery, Aristotle University of Thessaloniki,
      due to the presence of a mildly painful swelling in the left lateral chest wall,
      which was first noticed three months ago, after a blunt injury during sport.
      Physical examination revealed the presence of a palpable, spherical, painful, nut
      sized subcutaneous lesion in the left lateral chest wall, respectively, with the
      anterior axillary line, at the height of the 6th to 7th intercostal space.
      Presence of ecchymosis on the overlying skin was also noticed. During palpation,
      we did not notice fluctuation, while transillumination was not feasible.
      Performance of ultrasonography, including Doppler color flow imaging, followed,
      depicting a subcutaneous cystic lesion, 2.1*3.2 cm in dimensions, without
      extension to the thoracic cavity. Scheduled surgical excision of the lesion was
      decided. Histopathological examination documented the diagnosis of cystic
      lymphangioma. Patient is still followed up on a 6-month basis. He remains
      asymptomatic, after 2 years, without indication of relapse.

PMID- 29201482
TI  - Deletion Involving the 7q31-32 Band at the CADPS2 Gene Locus in a Patient with
      Autism Spectrum Disorder and Recurrent Psychotic Syndrome Triggered by Stress.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by
      impairments in social functioning, language, communication, and behavior. Recent
      genome-wide association studies show some microdeletions on the 7q31-32 region,
      including the CADPS2 locus in autistic patients. This paper reports the case of a
      patient with ASD and recurrent psychotic syndrome, in which a deletion on the
      7q31-32 band at the CADPS2 gene locus was evidenced, as well as a brief review of
      the literature on the CADPS2 gene and its association with ASD.

PMID- 29201483
TI  - Purulent Appearing Material in an Endobronchial Ultrasound-Guided Transbronchial
      Needle Aspiration of Mediastinal Lymph Node: A Diagnostic Challenge.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has
      increasingly been performed for the diagnosis and staging of thoracic
      malignancies. Findings of a necrotic lymph node raise concern for infectious
      process and malignancy. A hypoechoic area on ultrasound/EBUS within a lymph node
      without blood flow is suggestive of pathologies like infections or malignancy.
      Inspection of the fluid could suggest a diagnosis; clear aspirates usually
      suggest bronchogenic or mediastinal cysts and purulent material suggests
      abscesses or necrotic lymph nodes. Growing tumor cells require a blood supply; if
      the vascular stroma is insufficient due to rapidly growing malignant tumors this
      could lead to large central areas of ischemic necrosis. Necrotic aspiration of
      lymph nodes is not always of infectious etiology. Aspiration of fluid in EBUS
      TBNA is a rare occurrence, and malignancy should be considered when purulent
      fluid material is obtained. We present an elderly woman who underwent
      bronchoscopy with EBUS-TBNA for evaluation of upper lung nodule and mediastinal
      lymphadenopathy. Pus-like material was obtained on needle aspiration and
      endobronchial biopsy and mediastinal core biopsy revealed squamous cell
      carcinoma.

PMID- 29201484
TI  - Intracranial Myeloid Sarcoma Metastasis Mimicking Acute Subdural Hematoma.
AB  - Myeloid sarcoma, a rare consequence of myeloproliferative disorders, is rarely
      seen in the central nervous system, most commonly in the pediatric population.
      Although there are a handful of case reports detailing initial presentation of
      CNS myeloid sarcoma in the adult population, we have been unable to find any
      reports of CNS myeloid sarcoma presenting as a large mass lesion in a herniating
      patient. Here, we present the case of a patient transferred to our facility for a
      very large subdural hematoma. Based on imaging characteristics, it was felt to be
      a spontaneous hematoma secondary to coagulopathy. No coagulopathy was found.
      Interestingly, he did have a history of acute myeloid leukemia (AML) diagnosed 2
      months previously, and intraoperatively he was found to have a confluent white
      mass invading both the subdural and subarachnoid spaces. There was minimal
      associated hemorrhage and final pathology showed myeloid sarcoma. This is the
      first report we are aware of in which CNS myeloid sarcoma presented as a subdural
      metastasis and also the first report in which we are aware of this etiology
      causing a herniation syndrome secondary to mass effect.

PMID- 29201485
TI  - Retroperitoneal Ectopic Pregnancy: Diagnosis and Therapeutic Challenges.
AB  - Background: Retroperitoneal ectopic pregnancy is extremely rare. This unusual
      location represents a great challenge for clinicians due to the difficulties of
      diagnosis and high risk of life-threatening complications. Case Report: We report
      the case of a spontaneous early pregnancy of undetermined location in a patient
      with a history of previous laparoscopic surgery. Diagnosis steps using clinical
      examination, ultrasound, and magnetic resonance imaging led to the localization
      of the pregnancy, in the left side of the para-aortic region, in the
      retroperitoneal space. Conclusion: Retroperitoneal ectopic pregnancy is an
      uncommon entity with rather complex pathogenesis. Clinicians should carefully
      interpret clinical signs, biological findings, and imaging features and be aware
      of unusual locations such as the retroperitoneum for ectopic pregnancies. Early
      diagnosis and appropriate management strategy are conditio sine qua non for
      successful treatment outcomes.

PMID- 29201486
TI  - Gallstone Pancreatitis: A Common but Often Overlooked Cause of Abdominal Pain in
      Post-Liver-Transplant Patients.
AB  - Introduction: In general population, gallstone pancreatitis is the most common
      cause of pancreatitis. However, there are very few literatures that address this
      topic in post-liver-transplant patients. Clinical Case: A 69-year-old female who
      had a liver transplant in 2015 due to hepatocellular carcinoma and nonalcoholic
      steatohepatitis (NASH) cirrhosis. She had a recent episode of acute cellular
      rejection that was treated with high dose methylprednisolone 1 week prior to
      admission. She presented with severe epigastric abdominal pain associated with
      nausea and vomiting. Her laboratory studies showed significantly elevated serum
      lipase, AST, and ALT from her baseline. She underwent urgent Endoscopic
      Ultrasound (EUS) with Endoscopic Retrograde Cholangiopancreatography (ERCP) that
      showed common bile duct stone that was extracted. Discussion: Biliary sludge and
      stones accounted for 22% of late onset acute pancreatitis after liver transplant.
      Corticosteroids have been identified as one of the potential causes of drug
      induced pancreatitis. However, she is more likely to have gall stone pancreatitis
      since she also had dilated common bile duct and intrahepatic duct. In addition,
      there was CBD stone noted on ERCP. Conclusion: Acute gallstone associated
      pancreatitis after liver transplant is not uncommon. Patients generally have good
      outcomes. Further prospective studies are warranted.

PMID- 29201487
TI  - Primary Malignancy in a Supernumerary Testicle Presenting as a Large Pelvic Mass.
AB  - Supernumerary testis, also known as polyorchidism, is a condition characterized
      by the presence of more than two testes. Another condition of the testes is
      seminoma, a common cause of testicular germ cell tumor. A 35-year-old male was
      transferred to our hospital with a diagnosis of abdominal mass causing abdominal
      pain. On physical exam, he had a palpable undescended left testicle in the left
      inguinal canal, which was determined to be seminoma. The mass was surgically
      removed, and the patient underwent chemotherapy. The report discusses his workup,
      treatment, and outcome. This case illustrates an unusual presentation of
      supernumerary testis with the extra testis harboring a seminoma. When presented
      with a case of testicular cancer with no tumor noted in the palpable testes,
      malignancy in an extranumerary testicle should be considered in the differential.

PMID- 29201488
TI  - Left Brachiocephalic Vein Stenosis due to the Insertion of a Temporal Right
      Subclavian Hemodialysis Catheter.
AB  - Central vein stenosis/occlusion is a common well-described sequel to the
      placement of hemodialysis catheters in the central venous system. The precise
      mechanisms by which central vein stenosis occurs are not well known. Current
      concepts in central vein stenosis pathophysiology focus on the response to vessel
      injury model, emphasizing the process of trauma. A case of left brachiocephalic
      vein stenosis due to the insertion and function of a temporary right subclavian
      hemodialysis catheter is presented. The purpose of the manuscript is to emphasize
      that, with the introduction of a temporary subclavian hemodialysis catheter via
      the right subclavian vein apart from causing concurrent stenosis/infarction of
      the right subclavian and right brachiocephalic vein, it is also possible to cause
      stenosis of the left brachiocephalic vein (close to its contribution to the
      superior vena cava) although the catheter tip is placed in the correct anatomical
      position in the superior vena cava.

PMID- 29201489
TI  - Factors Affecting Health Related Quality of Life in Hospitalized Patients with
      Heart Failure.
AB  - This study identified factors affecting health related quality of life (HRQOL) in
      300 hospitalized patients with heart failure (HF). Data were collected by the
      completion of a questionnaire which included patients' characteristics and the
      Minnesota Living with Heart Failure Questionnaire (MLHFQ). Analysis of data
      showed that the median of the total score of MLHFQ was 46 and the median of the
      physical and mental state was 22 and 6, respectively. Also, participants who were
      householders or had "other" professions had lower score of 17 points and
      therefore better quality of life compared to patients who were civil/private
      employees (p < 0.001 and p < 0.001, resp.). Patients not receiving anxiolytics
      and antidepressants had lower quality of life scores of 6 and 15.5 points,
      respectively, compared to patients who received (p = 0.003 and p < 0.001, resp.).
      Patients with no prior hospitalization had lower score of 7 points compared to
      those with prior hospitalization (p = 0.002), whereas patients not retired due to
      the disease had higher score of 7 points (p = 0.034). Similar results were
      observed for the physical and mental state. Improvement of HF patients' quality
      of life should come to the forefront of clinical practice.

PMID- 29201490
TI  - 18F-FDG Pet-Guided External Beam Radiotherapy in Iodine-Refractory Differentiated
      Thyroid Cancer: A Pilot Study.
AB  - Introduction: To evaluate the clinical response rate after a postoperative 18F
      FDG PET/CT guided external beam radiotherapy (EBRT) in Iodine-refractory
      differentiated thyroid cancer. Material and Methods: Patients with thyroid cancer
      locally recurrent after total thyroidectomy plus metabolic radiotherapy and
      treated with radical EBRT were included. Inclusion criteria were detectable
      thyroglobulin (Tg), negative postmetabolic radiotherapy whole body scintigraphy,
      and no surgical indications. The pretreatment 18F-FDG PET/CT resulted positive in
      all cases (loggia, lymph nodes, and lung). EBRT was delivered with IMRT-SIB
      technique. A 18F-FDG PET/CT revaluation and Tg dosage were performed 3 months
      after the treatment. Results: Sixteen consecutive patients were included in this
      analysis (median follow-up: 6-44 months). Post-EBRT 18F-FDG PET/CT showed CR in
      43.7%, PR in 31.2%, SD in 25.0% patients, and PD due to lung metastases in 12.5%.
      Overall response rate was 75.0% (CI 95%: 41.4-93.3%). Tg levels decreased in
      75.0% with a median Delta of 68.0%. Two-year PFS and OS rates were 80.0% and
      93.0%, respectively. Acute G3 toxicity occurred in 18.7% and late G2 toxicity in
      12.5%. Conclusions: 18F-FDG PET/CT was useful in target definition for
      radiotherapy planning, identifying positive areas not detected with 131I
      scintigraphy. IMRT based EBRT was feasible and our results encourage future
      prospective studies. This clinical trial is registered with ID: NCT03191643.

PMID- 29201491
TI  - Simultaneous Determination of Six Active Components in Oviductus Ranae via
      Quantitative Analysis of Multicomponents by Single Marker.
AB  - A method, quantitative analysis of multicomponents by single marker (QAMS), was
      established in this article to investigate the quality control of a traditional
      Chinese medicine, Oviductus Ranae. 7-Hydroxycholesterol, 7-ketocholesterol, 4
      cholesten-3-one, stigmasterol, 7-dehydrocholesterol, and cholesterol were
      selected as the indexes of quality evaluation of Oviductus Rana. The
      determination was achieved on an Agilent HC-C18 column (4.6 mm * 250 mm, 5 MUm)
      using methanol with water (87 : 13 v/v) as mobile phase at the flow rate of 2.0
      mL/min. Cholesterol was used as an internal standard to determine the relative
      correction factors between cholesterol and other steroidal constituents in
      Oviductus Ranae. The contents of those steroidal constituents were calculated at
      the same time. To evaluate the QAMS method, an external standard method was used
      to determine the contents of six steroidal constituents. No significant
      difference was observed when comparing the quantitative results of QAMS with the
      results of external standard method. The proposed QAMS method was proved to be
      accurate and feasible based on methodological experiments. QAMS provided a
      simple, efficient, economical, and accurate way to control the quality of
      Oviductus Ranae.

PMID- 29201492
TI  - Agropastoral Mobility and Rangelands Multiple Uses in the Miombo Frontier Ecozone
      of Tabora Region, Western Tanzania.
AB  - This study aimed to examine the argument of environmental resource-use conflict
      as the primary cause of crop farmers and agropastoralists conflicts in Tabora
      Region, Tanzania. It explored the multiple interdependent phenomena that affect
      livelihoods relationships between crop farmers and agropastoralists and the
      nature of their continuing conflicts over the ecozonal resources. A primary
      dataset of the two groups' conflicts was used. An ex post facto and multistage
      sampling design was adopted. A total of 252 respondents were interviewed in three
      separate villages drawn from agroecological zones fringing the miombo woodland
      where such tensions are high. Data were analyzed using logistic regression.
      Results indicate that education (beta = -1.215, .297; p = .050), household size
      (beta = .958, 2.607; p = .017), herd size (beta = 4.276, 7.197; p = 0.001), farm
      size (beta = -1.734, .048; p = .176), the police (beta = -.912, 4.582; p = .043),
      and village leaders (beta = -.122, .885; p = .012) were the most potent
      predictors of causes of conflicts. The study found no support for demographic
      variables, like age, sex, marital status, income, duration of residence, and
      distance to resource base. The study recommends population growth control and
      strengthening of local institutions and recommends local communities to sustain
      management of natural resources base in the area.

PMID- 29201493
TI  - Analysis of Microbial Diversity in Soil under Ginger Cultivation.
AB  - Ginger is a perennial monocotyledonous herb, which can be used as both a
      vegetable and a medicinal plant. However, it is susceptible to various plant
      pathogens. Microbial diversity in soil is related closely to the health and
      productivity of plant crops including ginger. In the current study, we compared
      microbial diversity from soil samples under ginger cultivation (disease incidence
      of >50% [relatively unhealthy sample] versus disease incidence of <10%
      [relatively healthy sample]). The bacterial and fungal taxa were analyzed by
      Illumina-based sequencing, with 16S and ITS identification, respectively. Both
      bacterial and fungal OTUs were significantly more in the healthy soil sample than
      the unhealthy sample. Moreover, the dominant bacterial and fungal genera were
      detected to be different in each sample. Rhodanobacter and Kaistobacter were the
      dominant bacterial genera in the healthy sample, while Rhodoplanes and
      Bradyrhizobium were the dominant genera in the unhealthy sample. For fungal
      analysis, Cladosporium, Cryptococcus, and Tetracladium were the dominant genera
      in the healthy sample, while Lecanicillium, Pochonia, and Rhodotorula were the
      dominant genera in the unhealthy sample. Collectively, the basic information of
      microbial diversity in ginger soil is helpful for elucidating the ginger-microbe
      interactions and potentially selecting suitable plant growth-promoting
      rhizobacteria and biocontrol agents for ginger production.

PMID- 29201494
TI  - Rural Panel Surveys in Developing Countries: A Selective Review.
AB  - Rural panel surveys are the most appropriate means to provide data for studying
      the unprecedented rapid migration and urbanization currently taking place in
      China and other developing countries. To maximize heterogeneity in urbanization
      and development over the last three decades, we selected rural panel surveys from
      five Asian countries, including India, Indonesia, Nepal, Thailand, and China.
      This paper provides a selective review, focusing on their panel survey
      methodology, which is organized based on our proposed four basics of panel
      surveys - representativeness, retrospect-prospect, multilevel tracking, and
      temporality. We analyzed the strengths and weaknesses of the selected panel
      surveys to provide directions for designing future rural panel studies in China
      and elsewhere in the developing world.

PMID- 29201495
TI  - Determination of velocity correction factors for real-time air velocity
      monitoring in underground mines.
AB  - When there are installations of air velocity sensors in the mining industry for
      real-time airflow monitoring, a problem exists with how the monitored air
      velocity at a fixed location corresponds to the average air velocity, which is
      used to determine the volume flow rate of air in an entry with the cross
      sectional area. Correction factors have been practically employed to convert a
      measured centerline air velocity to the average air velocity. However, studies on
      the recommended correction factors of the sensor-measured air velocity to the
      average air velocity at cross sections are still lacking. A comprehensive airflow
      measurement was made at the Safety Research Coal Mine, Bruceton, PA, using three
      measuring methods including single-point reading, moving traverse, and fixed
      point traverse. The air velocity distribution at each measuring station was
      analyzed using an air velocity contour map generated with Surfer(r). The
      correction factors at each measuring station for both the centerline and the
      sensor location were calculated and are discussed.

PMID- 29201496
TI  - Platelets prime hematopoietic and vascular niche to drive angiocrine-mediated
      liver regeneration.
AB  - In mammals, the livers regenerate after chemical injury or resection of hepatic
      lobe by hepatectomy. How liver regeneration is initiated after mass loss remains
      to be defined. Here, we report that following liver injury, activated platelets
      deploy SDF-1 and VEGF-A to stimulate CXCR7+ liver sinusoidal endothelial cell
      (LSEC) and VEGFR1+ myeloid cell, orchestrating hepatic regeneration. After carbon
      tetrachloride (CCl4) injection or hepatectomy, platelets and CD11b+VEGFR1+
      myeloid cells were recruited LSEC, and liver regeneration in both models was
      impaired in thrombopoietin-deficient (Thpo-/-) mice lacking circulating
      platelets. This impeded regeneration phenotype was recapitulated in mice with
      either conditional ablation of Cxcr7 in LSEC (Cxcr7iDelta/iDelta) or Vegfr1 in
      myeloid cell (Vegfr1lysM/lysM). Both Vegfr1lysM/lysM and Cxcr7iDelta/iDelta mice
      exhibited suppressed expression of hepatocyte growth factor and Wnt2, two crucial
      trophogenic angiocrine factors instigating hepatocyte propagation. Of note,
      administration of recombinant thrombopoietin restored the prohibited liver
      regeneration in the tested genetic models. As such, our data suggest that
      platelets and myeloid cells jointly activate the vascular niche to produce pro
      regenerative endothelial paracrine/angiocrine factors. Modulating this
      "hematopoietic-vascular niche" might help to develop regenerative therapy
      strategy for hepatic disorders.

PMID- 29201497
TI  - Fibromodulin reduces scar formation in adult cutaneous wounds by eliciting a
      fetal-like phenotype.
AB  - Blocking transforming growth factor (TGF)beta1 signal transduction has been a
      central strategy for scar reduction; however, this approach appears to be
      minimally effective. Here, we show that fibromodulin (FMOD), a 59-kD small
      leucine-rich proteoglycan critical for normal collagen fibrillogenesis,
      significantly reduces scar formation while simultaneously increasing scar
      strength in both adult rodent models and porcine wounds, which simulate human
      cutaneous scar repair. Mechanistically, FMOD uncouples pro-migration/contraction
      cellular signals from pro-fibrotic signaling by selectively enhancing SMAD3
      mediated signal transduction, while reducing AP-1-mediated TGFbeta1 auto
      induction and fibrotic extracellular matrix accumulation. Consequently, FMOD
      accelerates TGFbeta1-responsive adult fibroblast migration, myofibroblast
      conversion, and function. Furthermore, our findings strongly indicate that, by
      delicately orchestrating TGFbeta1 activities rather than indiscriminately
      blocking TGFbeta1, FMOD elicits fetal-like cellular and molecular phenotypes in
      adult dermal fibroblasts in vitro and adult cutaneous wounds in vivo, which is a
      unique response of living system undescribed previously. Taken together, this
      study illuminates the signal modulating activities of FMOD beyond its structural
      support functions, and highlights the potential for FMOD-based therapies to be
      used in cutaneous wound repair.

PMID- 29201498
TI  - Sperm function tests in clinical practice.
AB  - Conventional semen analysis solely is not completely adequate to predict
      pregnancy outcomes. Therefore, advanced sperm function tests have been developed
      and introduced to clinical practice. These tests use different methods and
      techniques to evaluate different stages of fertilization steps. In this review,
      we reported some commonly used sperm function tests: sperm penetration assay,
      sperm-zona pellucida binding test (hemizona assay), acrosomal reaction test,
      hyaluronan binding test, hypo-osmotic swelling test, magnetic-activated cell
      sorting and zeta sperm selection. We discussed the literature concerning these
      tests, the utilization techniques and also purpose and mechanism of each test. We
      emphasized the importance of sperm function tests in predicting in vitro
      fertilization and pregnancy outcomes and in the management of infertile couples
      and also the limitations of these tests. Along with improvements in molecular
      biology techniques, we believe that more applicative and beneficial tests will be
      developed in the near future.

PMID- 29201499
TI  - Biparametric MRI of the prostate.
AB  - Biparametric Magnetic Resonance Imaging (bpMRI) of the prostate combining both
      morphologic T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) is
      emerging as an alternative to multiparametric MRI (mpMRI) to detect, to localize
      and to guide prostatic targeted biopsy in patients with suspicious prostate
      cancer (PCa). BpMRI overcomes some limitations of mpMRI such as the costs, the
      time required to perform the study, the use of gadolinium-based contrast agents
      and the lack of a guidance for management of score 3 lesions equivocal for
      significant PCa. In our experience the optimal and similar clinical results of
      the bpMRI in comparison to mpMRI are essentially related to the DWI that we
      consider the dominant sequence for detection suspicious PCa both in transition
      and in peripheral zone. In clinical practice, the adoption of bpMRI standardized
      scoring system, indicating the likelihood to diagnose a clinically significant
      PCa and establishing the management of each suspicious category (from 1 to 4),
      could represent the rationale to simplify and to improve the current
      interpretation of mpMRI based on Prostate Imaging and Reporting Archiving Data
      System version 2 (PI-RADS v2). In this review article we report and describe the
      current knowledge about bpMRI in the detection of suspicious PCa and a simplified
      PI-RADS based on bpMRI for management of each suspicious PCa categories to
      facilitate the communication between radiologists and urologists.

PMID- 29201500
TI  - Metabesity and urological cancers.
AB  - Metabolic syndrome is one of today's most important health problems. Due to
      increased prevalence of metabolic syndrome in society, studies done on this topic
      have increased in number. Although metabolic syndrome was previously considered
      to be important only for cardiovascular health, it has been learned that with new
      data, human health is compromised more thoroughly by metabolic syndrome and is
      also a danger to malignancy. As a result, a new definition in the form of
      metabesity has been introduced. In this review, available information on
      metabesity and urological cancers is presented.

PMID- 29201502
TI  - Robotic surgery and malpractice.
AB  - Robotic surgery has undergone exponential growth since the last two decades.
      Employment of new technologies in surgery creates many ethical challenges
      concerning the advantages and disadvantages different from conventional surgery,
      ensuring safety of the new technology, giving permission to surgeons for using
      new technology, the way of informing patients before undergoing a new technology
      or technique, and the responsibilities of surgeons, firms and hospitals to the
      patients etc. In this review, robotic surgery was discussed from malpractice
      perspective.

PMID- 29201501
TI  - Alternative therapies in patients with non-muscle invasive bladder cancer.
AB  - Bladder cancer (BC) is one of the leading causes of cancer-related deaths
      worldwide. Despite, the majority of the cases were diagnosed as non-muscle
      invasive bladder cancer (NMIBC) with favorable prognosis, it has tendency to
      recur or progress to a higher grade or stage. The first line treatment of
      patients with NMIBC is transurethral resection with adjuvant therapies primarily
      intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, in a portion
      of patients whose BCG treatment failed, alternative treatments may be required.
      Furthermore, intravesical BCG may be contraindicated in or untolerated by a group
      of patients. For these patients, some treatment options are readily available and
      a variety of them are currently under clinical investigation. In this review,
      these alternative therapies have been summarized.

PMID- 29201503
TI  - Animal ethics in laparoscopic urology training.
AB  - Laparoscopic urologic operating techniques are in widespread use throughout the
      world and because of various advantages, over the years they have virtually
      become a gold standard surgical intervention method. As laparoscopy is a
      painstaking technique to learn, the training consists of different stages. Within
      these stages of training, wet laboratory training where animals are used, is the
      most sensitive stage. The widespread use of experimental animals in medical
      research necessitated standardization and the establishment of certain
      regulations. This standardization and organization of laws and regulations
      started to be discussed in Europe approximately a century ago and have been
      established on a certain foundation. In this rewiev article, we discuss some
      important points and ethic rules about laparoscopic urologic training practiced
      on live animals.

PMID- 29201504
TI  - Effect of sildenafil citrate in testosterone induced benign prostate hyperplasia
      rat model.
AB  - Objective: Efficacy of treatments for benign prostate hyperplasia (BPH) is
      limited because the disease has complex etiopathogenesis. Recent studies have
      demonstrated the presence of phosphodiesterase-5 (PDE-5) receptors in prostate
      tissue. We investigated efficacy of sildenafil citrate in testosteron - induced
      BPH in rats. Material and methods: The rats were divided into three groups. Each
      groups had 7 rats. Group 1 was control group. Testosteron propionate 3 mg/kg/day
      was injected subcutaneously for two weeks in Group 2. The same procedure was done
      for Group 3 and sildenafil citrate was added to water at daily doses of 2 mg/kg
      for two weeks. The rats were euthanized with intraperitoneal pentobarbital. The
      body weights were measured and the prostates were removed. Results: The mean
      weights of rats were 288+/-31.93, 345+/-23.23 and 294+/-32.86 g in Groups 1, 2
      and 3, respectively. The mean prostate weights of rats were 0.74+/-0.18, 1.3+/
      0.13 and 0.72+/-0.24 g in Groups 1, 2, and 3, respectively. Group 2 had
      statistically significantly higher prostate weights than the other groups
      (p<0.01). Relative prostate weight is calculated with ratio of prostate weight to
      body weight. BPH group showed an increase in relative prostate weight compared
      with other groups with significant difference (p=0.036 and p=0.040). There was
      statistical difference for acinar area between Group 2 and the others, no
      significant difference of number of acini, interstitial space and epithelial
      thickness. Group 2 has more papillary projections per acini than the other
      groups. Conclusion: Favourable effect of sildenafil citrate on dimensions of
      prostate but not all on histological parameters was observed. We expect that PDE
      5 inhibitors might be a treatment option for BPH patients if the studies support
      our findings in the future.

PMID- 29201505
TI  - Is there a relation between priapism occurring after penile doppler
      ultrasonography and international erectile function index score and erection
      hardness score levels?
AB  - Objective: The relation between Erection Hardness Score (EHS) and The
      International Erectile Function Index (IIEF) Questionnaire- Erectile Function
      Domain Score (IIEF-EF score) used in erectile dysfunction (ED) evaluation and the
      prevalence of priapism after penile Doppler ultrasonography (PDU) was examined in
      this study. Material and methods: A total of 62 patients who had PDU were
      included in the study. Patients were divided into two groups; there were 33
      patients in IIEF-EF score <=10, EHS <2 group (Group 1) and 29 patients in IIEF-EF
      score >10, EHS >=2 group (Group 2). The two groups separated according to their
      scores were compared for age, body mass index (BMI), prevalence of priapism,
      vascular comorbidities and duration of erection. Results: When compared to Group
      2, median age, rate of vascular comorbidities rate and BMI were detected to be
      higher in Group 1 with IIEF-EF score <=10 and EHS <2. But contrary to age and
      rate of vascular comorbidities (p=0.035, p=0.049 respectively), higher BMI was
      detected to be statistically insignificant (p=0.093). Duration of erection, IIEF
      EF score and number of cases with priapism were significantly higher in Group 2
      with IIEF-EF score >10 and EHS >=2 (p<0.001, p=0.027, p=0.049 respectively).
      Conclusion: High IIEF-EF and EHS scores, younger ages and lower rates of vascular
      comorbidities in patients from whom PDU was demanded increase the prevalence of
      priapism.

PMID- 29201506
TI  - Protective role of resveratrol on testicular germ cells in mice with testicular
      toxicity.
AB  - Objective: The aim of the present study was to investigate the possible
      beneficial effects of resveratrol in mice subjected to vinyl cyclohexene
      dieposide (VCD) -induced testicular toxicity. Material and methods: A total of
      thirty- six Swiss albino male mice aged 28-days were used in the present study.
      The study was composed of two stages where mice which received or did not receive
      VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into
      control and resveratrol-treated groups in the first stage and into groups of VCD-
      and VCD+resveratrol-treated groups in the second stage. At the end of the
      experiments, relative testicular weight (TW/BW) and dry/wet weight of testis
      (TDW/TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E)
      staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum
      testosterone, LH and FSH levels were measured by a commercially available ELISA
      kit. Results: Resveratrol caused a dose-dependent increase in TW/BW and decrease
      in TDW/TWW (p<0.05). Resveratrol at a dose of 20 mg/kg resulted in an improvement
      in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity
      (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height
      of testicular seminipherous tubuli significantly after VCD exposure (p<0.001).
      Conclusion: Results of the present study suggest that resveratrol can be used as
      a protective and/or therapeutic agent particularly for cases with male
      infertility caused by testicular toxicity.

PMID- 29201507
TI  - Computed tomography based evaluation of prostatic fiducial marker migration
      between the periods of insertion and simulation.
AB  - Objective: The aim of this study was to determine whether significant fiducial
      marker migration occurs between the periods of prostatic marker insertion and
      computed tomography (CT) performed for radiotherapy planning and if a waiting
      period is necessary. Material and methods: Thirty-nine patients with prostate
      adenocarcinoma underwent fiducial marker insertion before radiotherapy between
      June 2013 and December 2015. Three markers were inserted by one radiologist under
      the guidance of transrectal ultrasonography. All patients underwent CT three
      hours after insertion to confirm the number and position of fiducial markers.
      Radiotherapy planning CT was performed on an average of 11 days (range 7-20)
      after insertion. CT images were imported into treatment planning system to
      analyze the position of fiducial markers. Point- based marker match algorithm was
      used to find the distance of marker migration. The mean and maximum distances
      between each fiducial markers were calculated. Results: The mean distance of
      migration was 1.029+/-0.42 mm (range 0.23-1.93 mm) and the maximum distance was
      1.361+/-0.59 mm (range 0.25-2.74 mm). The distance of marker migration was not
      statistically significant for the groups organized according to the timing of
      marker insertion, prostate volume, patient age, prostate specific antigen level
      and Gleason score. Conclusion: According to our results significant fiducial
      marker migration did not occur during the interval between insertion and
      treatment planning CT. It should be taken into consideration that performing
      simulation on the same day as marker insertion might prevent increased cost and
      delayed radiation therapy by saving the patients from extra visits to the clinic.

PMID- 29201508
TI  - How localized is pathologically localized prostate cancer? The use of secondary
      circulating prostate cells as a marker of minimal residual disease and their
      association with patient outcome.
AB  - Objective: To determine the prognostic value of secondary circulating prostate
      cells (CPCs) in men with pT2 prostate cancer treated with radical prostatectomy.
      Material and methods: Prospective observational study was performed in men with
      pathologically confined prostate cancer who had been treated with radical
      prostatectomy. CPCs were obtained by differential gel centrifugation from 8 mL
      venous blood and identified by standard immunocytochemistry using anti-Prostate
      Specific Antigen (PSA) monoclonal antibody. A positive test was defined as >=1
      PSA staining cell/blood sample. Biochemical failure was defined as a serum PSA
      >0.2 ng/mL. Age, PSA at diagnosis, pT2a versus pT2b/c, Gleason score and the
      presence/absence of CPCs were compared with patient outcomes using Kaplan-Meier
      curves and Cox's hazard model. Results: Hundred and ninety-one men participated
      in the study, 107 (44.0%) had pT2b/c disease, 25 (13.1%) had a Gleason score >=7,
      and 39 (20.4%) were positive for CPCs. Biochemical failure occurred in 39 (20.4%)
      patients which was associated with a Gleason score >= 7 and CPCs (+). Survival
      rates at 3, 5 and 10 years for men with CPC (-) and CPC (+) were 100%, 100% and
      89.6%, and 74.4%, 64.1% and 18.5% respectively (HR: 18.70). The median time to
      failure was 5.1 years in CPC (+) men versus 8.1 years in CPC (-) patients.
      Conclusion: Secondary CPC is a marker for minimal residual disease and it is
      associated with a worse prognosis. The lead time to failure over serum PSA is
      approximately 5 years. However they do not define whether the failure is local or
      systemic.

PMID- 29201509
TI  - Adrenocortical carcinoma: Single center experience.
AB  - Objective: Adrenocortical carcinoma is an aggressive endocrine malignancy with an
      annual incidence of 0.5-2 cases per million. The most important factors that
      determine prognosis are tumor stage at the time of diagnosis and the success of
      surgery. However, advanced age, large tumor size, hormone secretion, high Ki-67
      index (>10%), tumor necrosis and high mitotic activity are other factors
      associated with poor prognosis. In the present study, we aimed to evaluate the
      contribution of the patient and treatment- related factors to the prognosis in
      adrenocortical carcinoma. Material and methods: We included 15 adrenocortical
      carcinoma patients who were followed in our center between 2005 and 2015. The
      effects of age, gender, tumor size, type of operation, postoperative resection
      status and adjuvant treatment on disease-free survival and overall survival were
      analyzed. Results: Disease-free survival was 23.32+/-3.69 months and overall
      survival was 36.60+/-10.78 months. Gender, tumor size, tumor stage, type of
      operation, hormonal activity, presence of necrosis, recurrence and development of
      metastasis were not found to be associated with disease-free survival and overall
      survival (p>0.05). Postoperatively applied adjuvant treatments including
      mitotane, chemotherapy and radiotherapy did not significantly affect disease-free
      survival in our study, but statistically significant increase in overall survival
      was observed in patients getting adjuvant treatments (p=0.006). Conclusion:
      Adrenocortical carcinoma has poor prognosis and short overall survival, and in
      its clinical course, recurrence and development of metastasis can be commonly
      observed even after complete resection of the tumor. Therefore, the patients
      should be evaluated carefully while determining the surgical procedure during the
      preoperative period, and the operation and post-operative follow-up should be
      performed in experienced centers. However, due to the positive effects of
      adjuvant treatments on survival, all patients should be evaluated postoperatively
      for the necessity of adjuvant treatments, especially mitotane.

PMID- 29201510
TI  - The efficacy and utilisation of preoperative multiparametric magnetic resonance
      imaging in robot-assisted radical prostatectomy: does it change the surgical
      dissection plan?
AB  - Objective: We investigated the effect of the use of multiparametric prostate
      magnetic resonance imaging (mp-MRI) on the dissection plan of the neurovascular
      bundle and the oncological results of our patients who underwent robot-assisted
      radical prostatectomy. Material and methods: We prospectively evaluated 60
      consecutive patients, including 30 patients who had (Group 1), and 30 patients
      who had not (Group 2) mp-MRI before robot-assisted radical prostatectomy. Based
      on the findings of mp-MRI, the dissection plan was changed as intrafascial,
      interfascial, and extrafascial in the mp-MRI group. Two groups were compared in
      terms of age, prostate-specific antigen (PSA), Gleason sum scores and surgical
      margin positivity. Results: There was no statistically significant difference
      between the two groups in terms of age, PSA, biopsy Gleason score, final
      pathological Gleason score and surgical margin positivity. mp-MRI changed the
      initial surgical plan in 18 of 30 patients (60%) in Group 1. In seventeen of
      these patients (56%) surgical plan was changed from non-nerve sparing to
      interfascial nerve sparing plan. In one patient dissection plan was changed to
      non-nerve sparing technique which had extraprostatic extension on final
      pathology. Surgical margin positivity was similar in Groups 1, and 2 (16% and
      13%, respectively) although, Group 1 had higher number of high- risk patients. mp
      MRI confirmed the primary tumour localisation in the final pathology in 27 of of
      30 patients (90%). Conclusion: Preoperative mp-MRI effected the decision to
      perform a nerve-sparing technique in 56% of the patients in our study; moreover,
      changing the dissection plan from non-nerve-sparing technique to a nerve sparing
      technique did not increase the rate of surgical margin positivity.

PMID- 29201511
TI  - Robot-assisted radical perineal prostatectomy: first experience of 15 cases.
AB  - Objective: Minimally invasive techniques are increasingly evolving and preferred
      to reduce surgical induced morbidity and mortality and minimize the challenges of
      surgical techniques. Especially radical perineal prostatectomy (RPP) includes
      some challenges like working in a deep and narrow space and challenging
      ergonomics for the surgeons. Because of these issues open RPP is still performed
      in experienced centers. In order to reduce these difficulties, robot- assisted
      radical perineal prostatectomy (r-RPP) is developed. In this study, we report our
      first clinical results for r-RPP. Material and methods: Between November 2016 and
      February 2017, 15 patients underwent r-RPP in our center. Multiparametric
      magnetic resonance imaging was performed for all patients to exclude locally
      advanced disease. The patients with chronic obstructive pulmonary disease and
      locally advanced prostate cancer were not chosen for r-RPP method. The patient
      was positioned in the exaggerated lithotomy with 15 degrees of Trendelenburg
      position. After incision and dissection of subcutaneous tissue, dissection was
      advanced to the margin of posterior recto-urethral muscle fibers. Then a
      GelPOINT(r) device was placed and robotic system was docked. Results: The mean
      age of the patients was 60.2+/-7.8 years. The mean body mass index of the
      patients was 28.8+/-1.9 kg/m2. Four patients had previous major abdominal
      surgeries. Preoperative mean prostate specific antigen value was 7.3+/-2.4 ng/mL.
      The mean prostate volume was 40.8+/-12.4 cc. Mean perineal dissection time was
      60+/-10.1 minutes. Mean console time and total operation time was 95+/-11.3 and
      167+/-37.4 minutes, respectively. The mean time of postoperative catheterization
      was 8.3+/-1.7 days. Early continence rate was 40% after urethral catheter removal
      and at 3rd month of the surgery mean continence rate was 94% for all patients.
      Conclusion: We demonstrate that r-RPP is a feasible and efficient method. But
      still this method needs for further studies in this area.

PMID- 29201512
TI  - Safety and efficacy of silodosin and tadalafil in ease of negotiation of large
      ureteroscope in the management of ureteral stone: A prosective randomized trial.
AB  - Objective: To evaluate the safety and efficacy of silodosin and tadalafil in ease
      of negotiation of large size ureteroscope (8/9.8 Fr) in the management of
      ureteral stone. Material and methods: Between June 2015 and May 2016, 86 patients
      presented with ureteral stone of size 6-15 mm were on consent randomly assigned
      to 1 of 3 outpatient treatment arms: silodosin (Group A), tadalafil (Group B),
      and placebo (Group C). After two weeks of therapy 67 patients underwent
      ureteroscopy, and ureteral orifice configuration, ureteroscopic negotiation,
      ureteral dilatation, operating time, procedural complication and drug related
      side effects were noted in each group. Results: Ureteral negotiation was
      significantly better in Groups A (73.9%) and B (69.6%) as compared to Group C
      (38.1%) (p<0.01). Statistically significant difference was noted in the
      requirement for dilatation in Group C (71.4%) as compared to Groups A (26.1%) and
      B (39.1%) (p<0.01). Ureteral orifice was found to be more dilated in Groups A
      (69.6%) and B (60.9%) as compared to Group C (28.6%). Mean operating time was
      statistically lower in Groups A (35.2 min) and B (34.91 min) as compared to Group
      C (41.14 min) (p<0.01). Conclusion: Both silodosin and tadalafil not only relax
      ureteral smooth muscle but also help in forward propagation of large size
      ureteroscope (8/9.8 Fr) without any significant risk of adverse events.

PMID- 29201513
TI  - Comparison of the outcomes of complete supine percutaneous nephrolithotomy in
      patients with radiopaque and radiolucent kidney stones.
AB  - Objective: This study compared the stone opacity effect in patients who had
      radiopaque and radiolucent stones in percutaneous nephrolithotomy (PCNL) results.
      Material and methods: The medical records of 171 complete supine PCNL procedures
      were gathered. Patients were categorized into two groups: those with radiopaque
      (n=141) and those with radiolucent (n=30) stones. Kidney, ureter and bladder x
      ray was done a day after PCNL and Ultrasound imaging was done two weeks later to
      evaluate the stone free rate. A stone free result was defined as having less than
      4 mm residual stone size. Outcome parameters were compared by univariate analysis
      and those which were significantly different between the two groups were assessed
      by multivariate binary logistic regression analysis. Results: There were no
      significant differences in age, sex, body mass index, hypertension, diabetes
      mellitus, pre-surgery hemoglobin, pre-surgery serum creatinine, stone and also
      surgery-related parameters between the two groups. Stone free rate, surgery time,
      complication-related parameters, hemoglobin drop, serum creatinine and glomerular
      filtration rate (GFR) changes were similar in both groups based on univariate
      analysis. The radiopaque group had higher post-surgery GFR (p=0.04) and longer
      hospital stay (p=0.009). However, opacity had no effect on these outcomes after
      multivariate analysis. Higher post-surgery GFR was seen in patient with higher
      GFR before surgery (p<0.0001). Also, higher hemoglobin before surgery was
      correlated with less hospital stay (p=0.001). Conclusion: The complete supine
      percutaneous nephrolithotomy outcomes are similar in patients with radiopaque and
      radiolucent stones.

PMID- 29201514
TI  - Does antegrade JJ stenting affect the total operative time during laparoscopic
      pyeloplasty?
AB  - Objective: We aimed to show the effect of retrograde JJ stenting and
      intraoperative antegrade JJ stenting techniques on operative time in patients who
      underwent laparoscopic pyeloplasty. Material and methods: A total of 34 patients
      were retrospectively investigated (15 male and 19 female) with ureteropelvic
      junction obstruction. Of the patients stentized under local anesthesia
      preoperatively, as a part of surgery, 15 were retrogradely stentized at the
      beginning of the procedure (Group 1), and 19 were antegradely stentized during
      the procedure (Group 2). A transperitoneal dismembered pyeloplasty technique was
      performed in all patients. The two groups were retrospectively compared in terms
      of complications, the mean total operative time, and the mean stenting times.
      Results: The mean ages of the patients were 31.5+/-15.5 and 33.2+/-15.5 years
      (p=0.09), and the mean body mass indexes were 25.8+/-5.6 and 26.2.3+/-8.4 kg/m2
      in Group 1 and Group 2, respectively. The mean total operative times were 128.9+/
      38.9 min and 112.7+/-21.9 min (p=0.04); the mean stenting times were 12.6+/-5.4
      min and 3.5+/-2.4 min (p=0.02); and the mean rates of catheterization-to-total
      surgery times were 0.1 and 0.03 (p=0.01) in Group 1 and 2, respectively. The mean
      hospital stays and the mean anastomosis times were similar between the two groups
      (p>0.05). Conclusion: Antegrade JJ stenting during laparoscopic pyeloplasty
      significantly decreased the total operative time.

PMID- 29201515
TI  - A novel method in decision making for the diagnosis of anterior urethral
      stricture: using methylene blue dye.
AB  - Objective: The use of methylene blue dye (MB) to highlight anatomical structures
      in urology has been well-established. Urethral stricture may extend about a
      centimeter beyond the abnormal area seen on urethrogram. Although the current
      literature suggests a tension-free and end- to- end anastomosis after excision of
      the strictured urethral segment with spongiofibrosis and surrounding corpus
      spongiosum in short bulbar strictures, some centers dealing with urethroplasty
      prefer anastomosis for short bulbar strictures while others prefer augmentation.
      With this study, use of MB for delineating stricture line and assessing
      spongiofibrosis in the diagnosis of urethral stricture was evaluated. Material
      and methods: Five cc MB including 10 mg/mL is diluted with 10 cc saline. In the
      first scenario, MB is gently injected into urethra via the meatus before the
      urethroplasty procedure. Meanwhile, the extent of urethral segment stained by MB
      is noted. In the second scenario (MB spongiosography) in short bulbar stricture,
      insulin needles are inserted in spongiosa of the stricture site distally and
      proximally. MB is gently injected with distal needle. The two remaining needles
      are then observed. Presence of MB efflux in proximal needle implies deficiency of
      significant spongiofibrosis, so buccal augmentation is performed. Absence of
      efflux of MB implies significant spongiofibrosis and anastomotik site excised.
      Results: Four hundred and ninety-two consecutive cases prospectively evaluated
      between 2010 and 2014. Precise staining of stricture was successfully observed in
      464 (94%) patients. Grossly normal appearing urothelium remained pink.
      Histopathology confirmed that the stained urethra had a stricture. Of the 22
      short bulbar idiopathic strictures, in 18 (82%) MB was seen across the stricture
      and urethral transection was avoided. Anastomosis was performed in 4 (18%) cases
      where no MB went across the primary excision. There were no known allergic
      complications. Conclusion: MB aids in delineating the urethral lumen and exact
      site of stricture that needs augmentation. MB Spongiography in short bulbar
      strictures could be used as a beneficial guide in relation to the type of
      urethral repair to be performed in terms of augmentation versus excision and
      anastomosis.

PMID- 29201516
TI  - Effectiveness of spinal anesthesia combined with obturator nerve blockade in
      preventing adductor muscle contraction during transurethral resection of bladder
      tumor.
AB  - Objective: To determine whether spinal anesthesia combined with obturator nerve
      blockade (SOB) is effective in preventing obturator nerve stimulation, jerking
      and bladder perforation during transurethral resection of bladder tumor (TURBT).
      Material and methods: In this clinical trial, 30 patients were randomly divided
      into two groups: spinal anesthesia (SA) and SOB. In SA group, 2.5 cc of 0.5%
      bupivacaine was injected intrathecally using a 25-gauge spinal needle and in SOB
      after spinal anesthesia, a classic obturator nerve blockade was performed by
      using nerve stimulation technique. Results: There was a statistically significant
      difference between jerking in both groups (p=0.006). During the TURBT, surgeon
      satisfaction was significantly higher in SOB group compared to SA group
      (p=0.006). There was no significant correlation between sex, patient age and
      location of bladder tumor between the groups (p>0.05). Conclusion: Obturator
      nerve blockade by using 15 cc lidocaine 1% is effective in preventing adductor
      muscle spasms during TURBT.

PMID- 29201517
TI  - Long-term outcome of laparoscopic vesicouterine fistula repair: Experience from a
      tertiary referral centre.
AB  - Objective: Vesicouterine fistula (VUF) is an uncommon cause of female genito
      urinary fistula. Most of these fistulas are due to lower segment uterine cesarean
      section (LSCS). Traditionally, open surgical repair has been the traditional
      treatment. However, laparoscopic repair of VUF is a minimally invasive technique
      and few case reports have been published with short term follow up. In the
      present study, we are presenting our long- term outcome of laparoscopic repair of
      VUF. Material and methods: A retrospective analysis of 8 patients with VUF was
      performed from 2010 to 2015. Approval of Institutional Review Committee was
      obtained. All had history of LSCS of whom 3 had history of prolonged obstructed
      labor. Radiological imaging included ultrasound of kidney, ureter and bladder for
      all patients and hysterosalphingography in 4 patients and contrast enhanced
      computed tomography scan in 4 patients. Results: Median age of the patient was
      25.5 years (range, 22-32), and median follow up was 2.3 years (range, 1 -4). The
      most common presentation was cyclical menstrual bleeding through urine (menouria)
      in all, associated amenorrhea in 6 and vaginal leakage of urine in 2 cases. All
      patients underwent laparoscopic repair with successful outcomes. The mean
      operating time was 155+/-14.5 min (range, 135-186 min) with a median blood loss
      of 100 mL (range, 50-210 mL). Successful pregnancy was completed in 2 patients
      and other patients were taking contraceptives. Conclusion: Laparoscopic repair of
      VUF is a safe and effective minimally invasive technique with successful
      pregnancy in long- term follow up.

PMID- 29201518
TI  - Transobturator four arms mesh in the surgical management of stress urinary
      incontinence with cystocele.
AB  - Objective: This study aims to evaluate safety and efficacy of four arms
      polypropylene mesh in the long- term follow-up in the management of stress
      urinary incontinence (SUI) associated with cystocele. Material and methods: This
      prospective study was conducted on 50 female patients with SUI associated with
      cystocele. Patients underwent placement of transobturator four-arms mesh
      implants. Stress incontinence was evaluated using cough stress test with and
      without prolapse reduction, Stamey's grading of SUI, the validated Arabic version
      of the International Consultation on Incontinence Questionnaire-Short Form and
      King Health Questionnaire forms. Perioperative parameters evaluated included age,
      body mass index, grade of SUI, time of procedure, hospital stay after surgery,
      difference between pre-, and postoperative serum hemoglobin values, and need for
      blood transfusion. Follow- up visits were planned at 3, 9 and 18 months after
      surgery. Results: The mean operative time was 37.4+/-10.2 (25-60) minutes. Blood
      transfusion was not required. The mean hospital stay was 30.5+/-10 (24-48) hrs.
      Five (10%) patients had fever and urinary tract infections were noticed in five
      (10%) patients. Two (4%) women had urine retention after catheter removal and
      vaginal mesh erosion was present in one (2%) patient. Forty (80%) patients were
      cured from SUI, 8 (16%) patients were improved and 2 (4%) patients failed to
      respond. Conclusion: Cystocele associated with SUI can be repaired with
      transobturator four-arms mesh with promising results, improved quality of life,
      and tolerable side effects.

PMID- 29201519
TI  - Glans wings are separated ventrally by the septum glandis and frenulum penis: MRI
      documentation and surgical implications.
AB  - Objective: In the normal human penis, the glans wings are in apposition in the
      midline ventrally, and are separated by the "septum glandis" and "frenulum" of
      the prepuce. However, most of the hypospadias repair techniques include
      dissection of the glans wings and their approximation enclosing the neourethra
      within the glans. Material and methods: In order to obtain detailed information
      about the normal anatomy of glans penis, magnetic resonance imaging (MRI)
      findings of the penis were studied in three adults. Transverse, and sagittal
      sections of the penis were performed with a 1.5-T MRI scanner. Results: The
      present MRI study has confirmed that the glans wings do not fuse at the ventral
      midline and they are seperated by a fibrous tissue (septum glandis). This fibrous
      tissue is connected to the frenulum, traversing the wings of the glans penis. The
      glanular urethra forming the fossa navicularis has a wider caliber than the
      proximal urethra, and its walls are radiologically seen as the extension of that
      fibrous tissue. Conclusion: The male urethra is not a uniform tubular structure
      and has distinct attachments in glans penis. The glans wings are separated
      ventrally by the septum glandis and frenulum. In hypospadias, the septum glandis
      and frenulum are entirely missing structures. Therefore, in hypospadias surgery,
      the anatomical features of the glanular urethra must be taken into consideration.

PMID- 29201520
TI  - Transurethral incision of ureteroceles in paediatric age group.
AB  - Objective: Ureteroceles are a great clinical challenge because of variations in
      anatomy and clinical presentations. We present our experience with primary
      transurethral incision of ureteroceles in children. Material and methods: Data of
      thirteen children managed for ureterocele from 2009 to 2016 was retrospectively
      analyzed with respect to age, sex, clinical presentation and symptomatology, type
      and localization of ureterocele, investigations, surgical management and follow
      up. Results: A total of 13 patients with ureteroceles were managed. There were 7
      males and 6 females. Six were neonates with antenatal diagnosis of ureteroceles.
      Five patients presented with urinary tract infection and two were diagnosed
      during ultrasound for abdominal pain. The ureteroceles were on the right side in
      7 patients and left in 6 patients. Six patients had a duplex system-five on right
      side and bilateral in one. Two patients had ureteroceles in solitary kidney. Four
      patients had associated hydronephrosis and hydroureter and two had only
      hydronephrosis alone. One patient had bilateral grade III reflux in the bilateral
      lower moieties of the patient with bilateral duplex system. Two patients had
      poorly functioning kidney on radionuclide scan. All patients underwent
      cystoscopic incision of the ureteroceles. Eleven had intravesical ureteroceles
      and two had large caeco-ureteroceles. Two patients required ureteric
      reimplantation during follow-up. Conclusion: Though the approach of managing a
      patient with ureterocele should be individualized, transurethral incision remains
      valuable as a primary intervention with regular follow up. It may even prove to
      be the only intervention required in most of the patients.

PMID- 29201521
TI  - Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1
      biomarkers for predicting renal scar in children with urinary tract infection.
AB  - Objective: Urinary tract infection occurs in 1.8-6.6% of children under 6 years
      old. The aim of this study was to assess the urinary concentrations of matrix
      metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1),
      in children with acute pyelonephritis (APN) and the potential to develop renal
      scarring. Material and methods: Children who had experienced an episode of APN
      were divided into 2 groups. Group 1 included children with APN who exhibited
      scarring and group 2 included children with APN who had a normal 99mTechnetium
      dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in
      the acute phase of infection. A receiver operating characteristic curve was
      generated to allow calculation of cut-off values. Results: Sixty-one children
      were enrolled across the 2 groups: group 1 contained 16 patients (all female);
      group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1
      were significantly higher in group 1 than in group 2 (p=0.037 and 0.022
      respectively). For comparison of groups 1 and 2, the cut-off values were measured
      as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value,
      PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%,
      specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75%
      specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9*TIMP1 levels,
      respectively. Conclusion: Evaluation of urinary MMP9 and TIMP1 levels may help to
      identify children with APN who are at risk of developing renal scarring.

PMID- 29201522
TI  - Clinical effect of discordance in empirical treatment of cases with urinary tract
      infection accompanied by bacteremia.
AB  - Objective: It has been shown in previous studies that inadequate empirical
      treatment is associated with mortality in a variety of infections caused by Gram
      negative bacteria. In this study, the clinical effect of discordance in empirical
      treatment was investigated in patients with urinary tract infection (UTI)
      accompanied by bacteremia. Material and methods: We retrospectively reviewed the
      files of adult (>18 years old) patients who were diagnosed with UTI in our clinic
      between January 2014 and December 2015. Cases in which the same causative
      microorganism grew in both blood and urine cultures were included in the study.
      Patients using ceftriaxone and carbapenem as empirical antibiotic therapy (EAT)
      were compared as two different groups. In cases that the ethiologic agents were
      extended- spectrum beta lactamase (ESBL)-producing Klebsiella pneumoniae and
      Escherichia coli isolates, if the microorganism was resistant to initial
      antibiotic treatment the situation was defined as EAT discordance, and if it was
      sensitive it was defined as EAT concordance. Results: After the exclusion
      criteria were applied, 65 of the 266 cases examined were taken into the study.
      Clinical and laboratory features of cases of ceftriaxone and carbapenem groups
      were similar. There was no statistically significant difference between the two
      groups in terms of hospital stay and survival (p>0.05). Of 28 cases of ESBL
      producing E. coli and K. pneumoniae, 18 were EAT discordant and 10 were EAT
      concordant. Clinical and laboratory features of EAT concordant and EAT discordant
      groups were similar. No statistically significant difference was found between
      the two groups in terms of hospital stay and survival (p>0.05). Conclusion: It
      was considered that ceftriaxone can still be a viable option in the EAT of UTI,
      which is accompanied by bacteremia without severe sepsis and septic shock
      findings. It was concluded that EAT discordance may not have a negative effect on
      the duration of hospital stay and survival rates in neither total cases nor ESBL
      positive ones.

PMID- 29201523
TI  - Surgical complications of open nephrectomy in living related donors in Yemen: a
      prospective study.
AB  - Objective: Renal transplantation from living related donor is the best treatment
      option for chronic renal failure with experience for more than 50 years. However,
      this procedure may expose the health and even the life of otherwise normal
      individuals to risk. In this prospective study we described the surgical
      complications of open donor nephrectomies by Clavien grading system. Material and
      methods: Between May 2002 and December 2014, one hundred and seventy-two
      potentially healthy kidney donors were admitted to Althawrah General Hospital,
      Ibn-Sina Hospital and Military Hospital. The median age was 34 years (19-60
      years) with male predominance in 64.5% of the cases. This prospective descriptive
      study reviews intra-, and post-operative surgical complications using Clavien
      grading system for surgical complications. Results: The procedure was done via
      supracostal lumbotomy incision (above 12th rib) in 112 cases (65.1%) and
      transcostal incision with resection of 11th rib in 60 cases (34.9%). Left kidney
      was taken in most of the cases (68%) while right kidney in the remaining 42% with
      an average warm ischemia time of 31 seconds (range, 22-34 seconds). Surgical
      complications by Clavien grading system were observed in 18.6% of the cases (32
      cases). Grade 1 in 28 (16.4%); Grade 2 in 2 (1.2%) and Grade 3 in 2 cases (1.2%)
      were detected. There was no grade 4 or 5 cases in our series. Median
      postoperative hospital stay was 3 days (range: 2-4 days). Conclusion: We found
      that most of the complications of open living donor nephrectomy are of grade I
      and higher grade complications are negligible compared to the advantages for the
      recipients.

PMID- 29201524
TI  - Recent discovery of phallic depictions in prehistoric cave art in Asia Minor.
AB  - It was more recently announced by archeological society that cave art about human
      being dated back to 8,000 years ago had been discovered at southern Asia Minor.
      The primitive human figures involved the phallus pointing the ground almost the
      same size with legs. The cave artists represented their masterpiece without any
      exaggeration with the exception of extraordinary phallus. The erected penis is
      regarded as the symbol of giver of life and linked with the creator of the
      Universe in the initial period of art. In this article, the recent archeological
      findings were discussed in the light of andrological literature.

PMID- 29201525
TI  - Complete penile skin necrosis.
AB  - Superficial penile skin infections may be presented in different clinical
      situations that vary from simple infection to organ loss and serious morbidity
      and mortality. Antibiotic treatment and, if necessary, urgent debridement is
      required. A 46-year-old male patient with the complaints of urethral discharge
      and pain admitted to our outpatient clinic. He declared that there were midpenil
      tenderness and erythema 14 days ago which occurred after sexual intercourse.
      Complete penile skin necrosis with purulent discharge was detected in physical
      examination. After wound debridement and 14-days of intravenous antibiotic
      treatment, wound site culture was negative and then full-thickness skin grafting
      was performed. Urgent antibiotic treatment should be given, especially for the
      skin infections of the genital area. Despite the rapid spread of antibiotic
      treatment, clinical presentation may worsen within hours. It should be noted that
      especially in diabetics and elderly patients with poor hygiene, the infection may
      spread to anogenital region and may lead to fulminant necrotizing fasciitis which
      can present with severe morbidity and mortality. Reconstructive surgery is
      planned after the control of infection and according to the amount of tissue
      loss.

PMID- 29201526
TI  - Male infertility associated with de novo pericentric inversion of chromosome 1.
AB  - Inversion occurs after two breaks in a chromosome have happened and the segment
      rotates 180 degrees  before reinserting. Inversion carriers have produced
      abnormal gametes if there is an odd number crossing- over between the inverted
      and the normal homologous chromosomes causing a duplication or deletion.
      Reproductive risks such as infertility, abortion, stillbirth and birth of
      malformed child would be expected in that case. A 54-year- old male patient was
      consulted to our clinic for primary infertility. The routine chromosome study
      were applied using peripheral blood lymphocyte cultures and analyzed by giemsa
      trypsin-giemsa (GTG) banding, and centromer banding (C-banding) stains. Y
      chromosome microdeletions in the azoospermia factor (AZF) regions were analyzed
      with polymerase chain reaction. Additional test such as fluorescence in situ
      hybridization (FISH) was used to detect the sex-determining region of the Y
      chromosome (SRY). Semen analysis showed azoospermia. A large pericentric
      inversion of chromosome 1 46,XY, inv(1) (p22q32) was found in routine chromosome
      analysis. No microdeletions were seen in AZF regions. In our patient the presence
      of SRY region was observed by using FISH technique with SRY-specific probe. Men
      who have pericentric inversion of chromosome 1, appear to be at risk for
      infertility brought about by spermatogenic breakdown. The etiopathogenic
      relationship between azoospermia and pericentric inversion of chromosome 1 is
      discussed.

PMID- 29201527
TI  - Intratesticular calcified nodule.
AB  - Since calcified nodule of the testis is seen very rarely, its etiology and
      diagnostic approach are not fully known. There have been a few cases reported in
      the literature. The objective of this study was to review the literature and
      report the case of a 30-year-old patient, who applied to our clinic due to a
      suspicious stiffness in his testis and underwent partial orchiectomy.

PMID- 29201528
TI  - Bilateral renal cell carcinoma with leiomyomatous stroma: A rare entity diagnosed
      synchronously and treated surgically in a staged fashion.
AB  - Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies
      and 90-95% of kidney neoplasms. Renal cell carcinoma with leiomyomatous stroma
      (RCCLS) is an extremely rare histopathological entity based on available
      literature data. Herein, we report a 31-year-old male with incidentally detected
      synchronous bilateral renal masses who was eventually found to harbor RCCLS after
      being operated sequentially via nephron-sparing surgery.

PMID- 29201529
TI  - A rare case of lobulated complete renal fusion with multiple hila and
      vasculature.
AB  - Complete renal fusion without crossed renal ectopia denotes the medial fusion of
      the renal parenchyma (with or without changes in the microarchitecture) in the
      pelvis with anteriorly placed short ureters terminating into the bladder. This
      could be due to the failure of renal analgen to ascent, lateral migration, axial
      rotation, and persistence of primitive vascular supply. Though remain
      asymptomatic such cases warrant concomitant congenital anomalies of other organ
      systems as well as the microarchitecture changes in the renal parenchyma.

PMID- 29201531
TI  - Stigma, Partners, Providers and Costs: Potential Barriers to PrEP Uptake among US
      Women.
AB  - Background: Pre-Exposure Prophylaxis (PrEP) use has remained low among US women
      while significantly increasing among men who have sex with men. Besides lack of
      awareness, women face several social and structural barriers in gaining access to
      and using PrEP. Methods: Four focus group discussions with 20 HIV-negative women
      who live in the Washington DC metropolitan area. Results: The women expressed
      concerns about social and structural barriers to PrEP use. They were afraid that
      stigma related to using "HIV medicines" could affect PrEP use as well. They are
      worried that family and friends may question their reasons for taking anti
      retrovirals and suspect that they were HIV-positive. They expected hostile
      reactions from male partners, including accusations of infidelity and introducing
      mistrust in their relationships. Communicating with health care providers about
      sexual matters in general and their need for PrEP in particular were identified
      as further barriers. Women reported that providers rarely ask about risk
      behaviors related to HIV acquisition; that short visits hinder establishing a
      trusting relationship to discuss sensitive matters. They were concerned that
      disclosure of risk behaviors may result in judgmental responses and harsh
      treatment from providers. Lastly, women were concerned that PrEP costs, including
      insurance coverage and copays, would keep PrEP out of their reach. While
      cognizant of the potential barriers, women were unwavering in their determination
      to find ways to circumvent challenges to PrEP access. Conclusion: Social and
      structural barriers may impede women's access to PrEP despite their own reported
      interest. Continued efforts to reduce HIV stigma, improve patient-provider
      relationships and ensure affordability of PrEP may increase the likelihood that
      women will use this important prevention modality.

PMID- 29201532
TI  - Clinical presentation, epidemiology, neurophysiological findings, treatment and
      outcome of nonconvulsive status epilepticus: a 3-year prospective, hospital-based
      study.
AB  - Objective: This study reports the prevalence of Nonconvulsive Status Epilepticus
      (NCSE) in patients with altered mental status (AMS), and describes the clinical
      presentation, etiology, neurophysiological findings, neuroimaging, treatment, and
      outcome of NCSE in Qatar. Recording duration of continuous EEG monitoring was
      also discussed. Methods: This was a 3-year, prospective, hospital-based study
      involving patients with AMS and continuous EEG monitoring admitted to the
      Emergency and ICUs of Hamad Hospital, Qatar. Patients with confirmed diagnosis of
      NCSE were compared to the patients who did not show EEG and clinical features
      compatible with NCSE. Descriptive statistics in terms of mean with standard
      deviation, as well as frequency and percentages for categorical variables, were
      calculated; Student's t test as well as Chi-square tests or Fisher's exact tests
      were applied. Logistic regressions NSCE was performed using significance level
      0.05 for independent variables at univariate analysis. Results: Number of
      patients with AMS and continuous EEG monitoring was 250. Number of patients with
      EEG compatible with NCSE: 65 (age range, 12-79 ys; m, 37; f, 28). Number of
      controls (defined as patients with EEG not compatible with NCSE): 185 (age range,
      12-80 ys; m, 101; f, 84). Rate of occurrence of NCSE in patients with AMS: 26%.
      NCSE group was younger than controls (p < .001). Twenty patients with NCSE (31%)
      and 35 patients in the control group (19%) died. Death was more frequent in
      comatose NCSE compared to controls (p < .0007). NCSE proper and comatose NCSE had
      longer hospital stays than controls (p < .02 and p < .03, respectively). Complete
      recovery occurred in 26 NCSE patients (40%) and in 98 controls (53%) (p < .08).
      Twenty-one patients (31%) presented with refractory NCSE: 12 patients survived, 9
      died. Conclusion: This was the first prospective study reporting a high number of
      NCSE in Qatar, a small country in the MENA region. This prevalence (26%) was in
      the middle range. NCSE patients did not perform better than controls, outcome
      being worse with comatose NCSE. NCSE is an emergent condition warranting
      expedited diagnosis and management. Three days of continuous EEG monitoring were
      able to diagnose most cases of NCSE.

PMID- 29201533
TI  - tRNAs as primers and inhibitors of retrotransposons.
AB  - The functional relationship between tRNAs and retrotransposons have been known
      for more than 35 years. tRNAs are used as primer molecules to guide the reverse
      transcription of retrotransposons. Recently, tRNAs have also emerge as important
      players in the postranscriptional regulation of retrotransposons by means of tRNA
      derived small RNAs. This surprisingly new layer of regulation indicates that
      tRNAs are used both in the promotion and the suppression of the reverse
      transcription of retrotransposons indicating their primary role in the life cycle
      of LTR retrotransposons. This adds another level of translational control to
      tRNAs. Here we review the different known levels of interactions of tRNAs and
      retrotransposons and highlight the unknown parts of this interaction.

PMID- 29201534
TI  - A Riemannian Framework for Linear and Quadratic Discriminant Analysis on the
      Tangent Space of Shapes.
AB  - We present a Riemannian framework for linear and quadratic discriminant
      classification on the tangent plane of the shape space of curves. The shape space
      is infinite dimensional and is constructed out of square root velocity functions
      of curves. We introduce the notion of mean and covariance of shape-valued random
      variables and samples from a tangent space to the pre-shapes (invariant to
      translation and scaling) and then extend it to the full shape space (rotational
      invariance). The shape observations from the population are approximated by
      coefficients of a Fourier basis of the tangent space. The algorithms for linear
      and quadratic discriminant analysis are then defined using reduced dimensional
      features obtained by projecting the original shape observations on to the
      truncated Fourier basis. We show classification results on synthetic data and
      shapes of cortical sulci, corpus callosum curves, as well as facial midline curve
      profiles from patients with fetal alcohol syndrome (FAS).

PMID- 29201535
TI  - Polymer Informatics: Opportunities and Challenges.
AB  - We are entering an era where large volumes of scientific data, coupled with
      algorithmic and computational advances, can reduce both the time and cost of
      developing new materials. This emerging field known as materials informatics has
      gained acceptance for a number of classes of materials, including metals and
      oxides. In the particular case of polymer science, however, there are important
      challenges that must be addressed before one can start to deploy advanced machine
      learning approaches for designing new materials. These challenges are primarily
      related to the manner in which polymeric systems and their properties are
      reported. In this viewpoint, we discuss the opportunities and challenges for
      making materials informatics as applied to polymers, or equivalently polymer
      informatics, a reality.

PMID- 29201536
TI  - The Challenges of Nutritional Assessment in Cirrhosis.
AB  - Purpose of Review: Nutritional status in patients with cirrhosis is very
      frequently associated with macro- and micronutrient deficiencies. Cirrhosis
      itself is the cause of malnutrition and nutritional deficiencies but these
      conditions have to be identified and addressed properly as they can worsen the
      prognosis of cirrhosis. The goals of this review are to 1) identify and describe
      the challenges associated with nutritional assessment in cirrhosis and 2)
      describe recent advancements when using clinical, laboratory, and instrumental
      tools in the evaluation of malnourished patients with liver diseases. Recent
      Findings: The most promising tools for nutritional assessment in cirrhosis
      include the evaluation of body composition with phase angle obtained by
      bioelectrical impedance analysis, computed tomography transverse images at the
      level of third lumbar vertebra. The Royal-Free Hospital global assessment
      algorithm appears to be helpful but needs further validation. Summary:
      Nutritional assessment in cirrhosis is challenging as several factors, including
      edema, can interfere with it and because of lack of a validated gold standard.
      Regardless, nutritional assessment methods have been developed in recent years
      and should gain relevance in the clinical practice.

PMID- 29201537
TI  - Electrical stimulation improved cognitive deficits associated with traumatic
      brain injury in rats.
AB  - Introduction: Cognitive deficits associated with traumatic brain injury (TBI)
      reduce patient quality of life. However, to date, there have been no effective
      treatments for TBI-associated cognitive deficits. In this study, we aimed to
      determine whether electrical stimulation (ES) improves cognitive deficits in TBI
      rats. Methods: Rats were randomly divided into three groups: the Sham control
      group, electrical stimulation group (ES group), and No electrical stimulation
      control group (N-ES group). Following fluid percussion injury, the rats in the ES
      group received ES treatment for 3 weeks. Potent cognitive function-relevant
      factors, including the escape latency, time percentage in the goal quadrant, and
      numbers of CD34+ cells, von Willebrand Factor+ (vWF +) vessels, and circulating
      endothelial progenitor cells (EPCs), were subsequently assessed using the Morris
      water maze (MWM) test, immunohistochemical staining, and flow cytometry. Results:
      Compared with the rats in the N-ES group, the rats in the ES group exhibited a
      shorter escape latency on day 3 (p = .025), day 4 (p = .011), and day 5 (p =
      .003), as well as a higher time percentage in the goal quadrant (p = .025) in the
      MWM test. After 3 weeks of ES, there were increased numbers of CD34+ cells (p =
      .008) and vWF + vessels (p = .000) in the hippocampus of injured brain tissue in
      the ES group compared with those in the N-ES group. Moreover, ES also
      significantly increased the number of EPCs in the peripheral blood from days 3 to
      21 after TBI in the ES group (p < .05). Conclusions: Taken together, these
      findings suggest that ES may improve cognitive deficits induced by TBI, and this
      protective effect may be a result, in part, of enhanced angiogenesis, which may
      be attributed to the increased mobilization of EPCs in peripheral blood.

PMID- 29201538
TI  - Vision In Stroke cohort: Profile overview of visual impairment.
AB  - Aim: To profile the full range of visual disorders from a large prospective
      observation study of stroke survivors referred by stroke multidisciplinary teams
      to orthoptic services with suspected visual problems. Methods: Multicenter
      prospective study undertaken in 20 acute Trust hospitals. Standardized
      screening/referral forms and investigation forms documented data on referral
      signs and symptoms plus type and extent of visual impairment. Results: Of 1,345
      patients referred with suspected visual impairment, 915 were recruited (59% men;
      mean age at stroke onset 69 years [SD 14]). Initial visual assessment was at
      median 22 days post stroke onset. Eight percent had normal visual assessment. Of
      92% with confirmed visual impairment, 24% had reduced central visual acuity <0.3
      logMAR and 13.5% <0.5 logMAR. Acquired strabismus was noted in 16% and acquired
      ocular motility disorders in 68%. Peripheral visual field loss was present in
      52%, most commonly homonymous hemianopia. Fifteen percent had visual inattention
      and 4.6% had other visual perceptual disorders. Overall 84% were visually
      symptomatic with visual field loss the most common complaint followed by blurred
      vision, reading difficulty, and diplopia. Treatment options were provided to all
      with confirmed visual impairment. Targeted advice was most commonly provided
      along with refraction, prisms, and occlusion. Conclusions: There are a wide range
      of visual disorders that occur following stroke and, frequently, with visual
      symptoms. There are equally a wide variety of treatment options available for
      these individuals. All stroke survivors require screening for visual impairment
      and warrant referral for specialist assessment and targeted treatment specific to
      the type of visual impairment.

PMID- 29201539
TI  - Assessment of cerebral blood flow with magnetic resonance imaging in children
      with sickle cell disease: A quantitative comparison with transcranial Doppler
      ultrasonography.
AB  - Introduction: Transcranial Doppler ultrasonography (TCD) is a clinical tool for
      stratifying ischemic stroke risk by identifying abnormal elevations in blood flow
      velocity (BFV) in the middle cerebral artery (MCA). However, TCD is not effective
      at screening for subtle neurologic injury such as silent cerebral infarcts. To
      better understand this disparity, we compared TCD measures of BFV with tissue
      level cerebral blood flow (CBF) using arterial spin-labeling MRI in children with
      and without sickle cell disease, and correlated these measurements against
      clinical hematologic measures of disease severity. Methods: TCD and MRI
      assessment were performed in 13 pediatric sickle cell disease patients and eight
      age-matched controls. Using MRI measures of MCA diameter and territory weight,
      TCD measures of BFV in the MCA [cm/s] were converted into units of CBF [ml min
      1100 g-1] for comparison. Results: There was no significant association between
      TCD measures of BFV in the MCA and corresponding MRI measures of CBF in patients
      (r = .28, p = .39) or controls (r = .10, p = .81). After conversion from BFV into
      units of CBF, a strong association was observed between TCD and MRI measures (r =
      .67, p = .017 in patients, r = .86, p = .006 in controls). While BFV in the MCA
      showed a lack of correlation with arterial oxygen content, an inverse association
      was observed for CBF measurements. Conclusions: This study demonstrates that BFV
      in the MCA cannot be used as a surrogate marker for tissue-level CBF in children
      with sickle cell disease. Therefore, TCD alone may not be sufficient for
      understanding and predicting subtle pathophysiology in this population,
      highlighting the potential clinical value of tissue-level CBF.

PMID- 29201540
TI  - Erythropoietin regulates immune/inflammatory reaction and improves neurological
      function outcomes in traumatic brain injury.
AB  - Introduction: Traumatic brain injury (TBI) remains a leading cause of disability
      and death among young people in China. Unfortunately, no specific pharmacological
      agents to block the progression of secondary brain injury have been approved for
      clinical treatment. Recently, neuroprotective effects of erythropoietin (EPO)
      have been demonstrated in addition to its principal function in erythropoiesis,
      and hence it is viewed as a potential drug for TBI. In this study, we have
      investigated the neuroprotective effects of EPO associated with
      immune/inflammatory modulation in a mouse experimental TBI model. Methods: EPO
      (5000 U/kg body weight, i.p.) was injected at 1 hr, 1, 2, and 3 days after TBI,
      and its effect on cognitive function, brain edema, immune/inflammatory cells
      including regulatory T cells (Tregs), neutrophils, CD3+ T cells, and microglia,
      cytokines including interleukin-10 (IL-10), transforming growth factor-beta (TGF
      beta), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha)
      were evaluated at different time points after treatment. Results: EPO treatment
      significantly decreased brain edema and improved cognitive function when compared
      to Saline-treated mice (p < .05). EPO treatment also significantly increased
      Tregs level in spleen and injured brain tissue as well as significantly reduced
      the infiltration and activation of immune/inflammatory cells (neutrophils, CD3+T
      cells, and microglia) in the injured hemisphere compared to Saline-treated
      control animals (p < .05). In addition, ELISA analysis demonstrated that EPO
      treatment increased the expression of anti-inflammatory cytokine IL-10, but
      decreased the expression of proinflammatory cytokine IL-1beta and TNF-alpha in
      the injured brain tissue (p < .05). Conclusions: These findings suggest that EPO
      could improve neurological and cognitive functional outcomes as well as regulate
      immune/inflammatory reaction in TBI.

PMID- 29201541
TI  - Pulsed radiofrequency stimulation suppresses palmar hyperhidrosis in an animal
      study.
AB  - Objectives: Palmar hyperhidrosis (PH) exhibits excessive and unpredictable
      sweating. The most effective treatment for permanent cure is the ablation of
      thoracic sympathetic ganglia innervating hands. However, sympathectomy of T2
      sympathetic ganglion by clipping or cauterization causes irreversible nerve
      damage, and results in a compensatory hyperhidrosis (CH). We herein used the
      pulsed radiofrequency (PRF) stimulation to reversibly block sympathetic ganglion
      to treat PH and avoid CH. Material and Methods: A bipolar electrode was implanted
      into the right T2 sympathetic trunk by endoscopic surgery and PRF was delivered
      through the electrode. The humidity (%) of right palm was measured to indicate
      sweating level. Results: Six out of 13 rats (46.2%) that received a 5-min PRF
      stimulation on the T2 sympathetic trunk showed a decrease in the right palm
      humidity during the surgery. PRF stimulation significantly reduced humidity from
      69.17% +/- 0.72% obtained from baseline condition to 66.93% +/- 0.69%. The
      humidity reduction was also observed at 10 min after the PRF stimulation. We
      further evaluated the effect of PRF stimulation 1 week after surgery and found
      that the PRF stimuli reduced right hand humidity in 5 out of 8 rats (62.5%). PRF
      stimulation significantly reduced humidity from 66.11% +/- 0.81% obtained from
      sham operation control to 63.62% +/- 0.82%. The percentage of right hand humidity
      obtained 10 min after PRF stimulation was also reduced to 63.38% +/- 0.80%.
      Anesthetics have no effect on humidity. Conclusions: These results indicate that
      PRF stimulation of T2 sympathetic trunk reduces palm sweating in rats.

PMID- 29201544
TI  - Occurrence of overt seizures in comatose survivor patients treated with targeted
      temperature.
AB  - Background: Unconscious patients after out-of-hospital cardiac arrest have a high
      risk of death. Therapeutic hypothermia is recommended by international
      resuscitation guidelines in order to attenuate secondary destructive
      physiological processes such as reperfusion injury, apoptosis, and cerebral
      edema. The target temperature to reach ranges between 32 and 34 degrees C for at
      least 24 hr. Hypothermia can induce metabolic disturbances. There are some
      reports in the literature indicating the presence of seizures during targeted
      temperature management. On the other hand, postanoxic seizures are a sign of
      unfavorable neurological outcome. The purpose of this study was to evaluate the
      occurrence of overt seizures in comatose survivor patients treated with targeted
      temperature in respect to overt seizures in a normal temperature group of
      comatose patients. Methods: This was a retrospective study of unconscious adults
      post cardiopulmonary resuscitation, hospitalized in the intensive care unit
      during the years 2008-2015. The patients were divided into two groups: those
      treated with hypothermia and those with normal body temperature. Both groups were
      evaluated for the appearance of overt seizures during their hospitalization which
      was the primary outcome of the study. Results: The data of 88 consecutive
      unconscious patients after out-of-hospital cardiac arrest were collected. Twenty
      six patients were treated with targeted temperature (32-34 degrees C) and 62
      patients with normal temperature. In the hypothermic group, 6 (23%) patients
      developed overt seizures during hospitalization compared to 11 (17%) in the
      normothermic group. The mortality rate was similar in both groups, 16 (61%) in
      the hypothermic group and 38 (61%) in the conservative group. According to the
      present study, overt seizures were more common in the group treated with
      hypothermia.

PMID- 29201542
TI  - Plasma sphingolipids and depressive symptoms in coronary artery disease.
AB  - Background: Depression is highly prevalent in individuals with coronary artery
      disease (CAD) and increases the risk of future cardiac events and mortality.
      Sphingolipids have been implicated in the pathophysiology of both CAD and
      depression. This study assessed the association between plasma sphingolipid
      concentrations and depressive symptoms in CAD subjects. Methods: Depressive
      symptoms were measured using the depression subscale of the self-reported
      Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were
      measured from fasting plasma samples using high-performance liquid chromatography
      coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear
      regression models were used to assess associations between log-transformed
      concentrations of plasma sphingolipids and depressive symptoms. Results: A total
      of 111 CAD patients (mean (SD) age = 63.6 +/- 6.4, 84.7% male) were included. In
      linear regression analyses, higher plasma concentrations of ceramides C16:0 (beta
      = 0.204, p = .026) and C18:0 (beta = 0.209, p = .023) and sphingomyelin SM18:1
      (beta = 0.210, p = .024) were significantly associated with higher HADS
      depression subscale score after adjusting for covariates. Conclusion:
      Sphingolipids, in particular the ceramide species C16:0 and C18:0 and the
      sphingomyelin species SM18:1, may be implicated in the pathophysiology of
      depression in CAD. The association between plasma sphingolipid concentrations and
      depression should be further examined in CAD patients and in other populations.

PMID- 29201543
TI  - Object words modulate the activity of the mirror neuron system during action
      imitation.
AB  - Background: Although research has demonstrated that the mirror neuron system
      (MNS) plays a crucial role in both action imitation and action-related semantic
      processing, whether action-related words can inversely modulate the MNS activity
      remains unclear. Methods: Here, three types of task-irrelevant words (body parts,
      verbs, and manufactured objects) were presented to examine the modulation effect
      of these words on the MNS activity during action observation and imitation.
      Twenty-two participants were recruited for the fMRI scanning and remaining data
      from 19 subjects were reported here. Results: Brain activity results showed that
      word types elicited different modulation effects over nodes of the MNS (i.e., the
      right inferior frontal gyrus, premotor cortex, inferior parietal lobule, and
      STS), especially during the imitation stage. Compared with other word conditions,
      action imitation following manufactured objects words induced stronger activation
      in these brain regions during the imitation stage. These results were consistent
      in both task-dependent and -independent ROI analysis. Conclusion: Our findings
      thus provide evidence for the unique effect of object words on the MNS during
      imitation of action, which may also confirm the key role of goal inference in
      action imitation.

PMID- 29201545
TI  - Different patterns of attentional bias in antenatal and postpartum depression.
AB  - Background: Biased information processing in attention, memory, and
      interpretation is proposed to be central cognitive alterations in patients with
      major depressive disorder, but studies in women with peripartum depression are
      scarce. Because of the many similarities with depression in nonperipartum states
      as regards symptom profile and risk factors, we hypothesized that women with
      antenatal and postpartum depression would display attentional bias to negatively
      and positively valenced words. Methods: One hundred and seventy-seven pregnant
      and 157 postpartum women were included. Among these, 40 suffered from antenatal
      depressive disorder and 33 from postpartum depressive disorder. An emotional
      Stroop task with neutral, positive, negative, and negatively valenced obstetric
      words was used. Results: No significant difference in emotional interference
      scores was noted between women with antenatal depression and nondepressed
      pregnant women. In contrast, women with postpartum depression displayed shorter
      reaction times to both positive (p = .028) and negative (p = .022) stimuli,
      compared with neutral words. Pregnant women on antidepressant treatment displayed
      longer reaction times to negatively valenced obstetric words in comparison with
      untreated depressed women (p = .012), and a trend toward greater interference in
      comparison with controls (p = .061). Conclusions: In contrast with the
      hypothesis, we found no evidence of attentional bias to emotionally valenced
      stimuli in women with untreated peripartum depression. However, the shorter
      reaction times to emotional stimuli in women with postpartum depression may
      indicate emotional numbing, which in turn, is a functional impairment that may
      have repercussions for child development and well-being. Our findings emphasize
      the need to identify and treat women with postpartum depression at the earliest
      possible time point to ensure swift recovery and support for the family.

PMID- 29201546
TI  - Neurologists dealing with sickness certification: Experiences of problems and
      need of competence.
AB  - Rationale and Aims: Most studies on physicians' sickness certification practices
      include general practitioners (GP) while there hardly is any knowledge on this
      regarding neurologists although neurological diseases often involve work
      incapacity and need of sick leave. Aim: The aim was to describe experiences among
      neurologists in Sweden concerning their work with sickness certification of
      patients. Method: A cross-sectional study of 265 neurologists' responses in a
      nationwide survey regarding their work with sickness certification of patients
      was conducted. Results: The majority (81.5%) had sickness certification
      consultations at least once a week and a third experienced problems every week in
      handling sickness certification. Among the 251 who at least sometimes had
      sickness certification consultations, the following two aspects were experienced
      as very or fairly problematic: "assess the degree to which the reduced functional
      capacity limits a patient's capacity to perform his/her work assignments" (67.3%)
      and "make a long-term prognosis about the future work capacity of patients on
      sick leave" (60.5%). At least once a week, 78.7% experienced lack of time
      regarding managing patient-related aspects of the sickness certification task.
      Moreover, 21.8% considered sickness certification to be a work environmental
      problem, at least once a week. In all, 84% stated that they had a large or fairly
      large need for more competence concerning sickness certification tasks.
      Conclusions: Sickness certification is a common task among neurologists,
      involving several problematic aspects related to, e.g., lack of competence in
      assessing function and work capacity and of time. There is a need for
      improvement.

PMID- 29201547
TI  - Decremental responses in patients with motor neuron disease.
AB  - Objective: Involvement of the neuromuscular junction (NMJ) in amyotrophic lateral
      sclerosis (ALS) has been reported and is increasingly recognized as an important
      pathophysiological aspect. The relationship between decrement and clinical
      measures for possible application as a biomarker has not been comprehensively
      explored. Methods: We performed routine repetitive nerve stimulation (RNS) of
      three nerves on patients with ALS. We captured measures of muscle strength, grip
      strength, fatigability, and calculated slow vital capacity (SVC) rates of change
      assessing for associations. Results: In 42 subjects, 210 muscles were studied.
      Negative correlation was found between the percentage of decrement and compound
      muscle action potential (CMAP) amplitude. Approximately half of the patients with
      hand weakness did not have decrement. There was no significant correlation
      between decrement and handgrip fatigue, SVC < 80% predicted, or more rapid
      worsening of SVC over time. Conclusions: Abnormal decremental responses are well
      described in ALS. We report that the degree of decremental response does not
      correlate with the degree of weakness. Abnormal decrement is only rarely present
      in nerve-muscle pairs with normal motor power. Our findings did not support a
      correlation between abnormal decrement and clinical measures suggesting that RNS
      may not be useful as a biomarker to monitor ALS progression.

PMID- 29201548
TI  - Risk factors of carotid plaque and carotid common artery intima-media thickening
      in a high-stroke-risk population.
AB  - Introduction: To analyze the risk factors of carotid plaque (CP) and carotid
      common artery intima-media thickening (CCAIMT) and the association between the
      risk factors and CP numbers and the side of the CCAIMT in a high-stroke-risk
      population. Methods: Carotid ultrasonography was conducted in 2025 participants
      with high stroke risk. Participants were divided into different groups according
      to the results of the ultrasound. The risk factors and blood biochemical indices
      were recorded. Results: The presence of CP and CCAIMT were 38.9% and 24.8%
      respectively. Multivariate logistic regression indicated that the risk factors of
      CP were age, high LDL-C and FBG levels, male gender, stroke, diabetes,
      hypertension, and tobacco use. Compared with participants without CPs, the
      participants who were male, and older in age, with risk factors of tobacco use,
      diabetes, high LDL-C levels, and a family history of hypertension were likely to
      have a single CP, whereas the participants with risk factors of tobacco use,
      diabetes, hypertension, male gender, older age, high LDL-C levels, stroke and AF
      or valvulopathy were prone to have multiple CPs. The risk factors of CCAIMT were
      male gender, stroke, hypertension, diabetes, AF or valvulopathy, tobacco use and
      age. Compared with the N-CCAIMT subgroup, the risk factors of left CCAIMT were
      tobacco use, diabetes, male gender, and age. The risk factors of right CCAIMT
      were male gender, high FBG levels, age, AF or valvulopathy. The risk factors of
      dual CCAIMT were high frequency of drinking milk, tobacco use, male gender, age,
      stroke, and hypertension. Conclusion: These findings revealed the risk factors of
      CP and CCAIMT, and an association between the risk factors and the CP numbers and
      the side of the CCAIMT.

PMID- 29201549
TI  - l-Dopa/carbidopa intestinal gel and subthalamic nucleus stimulation: Effects on
      cognition and behavior.
AB  - Objective: In Parkinson's disease (PD), effects on behavior and cognition of
      levodopa/carbidopa intestinal gel (LCIG) and subthalamic stimulation (STN-DBS)
      and their practical consequences remain controversial. This study was designed to
      analyze the possible effects of these therapies on cognition and behavior after 1
      year follow-up. Methods: This was an open-label, nonrandomized prospective study
      for pre- and postintervention analyses. Twenty-four patients were considered
      eligible to be candidates for complex therapies such as STN-DBS or LCIG; 23
      patients treated with standard medication were included as controls. Several
      cognitive, behavioral, and motor scales were administered before and at 6 and 12
      months after the intervention. Results: Patients treated with LCIG experienced
      significant improvement in specific neuropsychological functions when compared
      with patients receiving STN-DBS and conventional medical treatment after 1 year
      from the onset of the intervention. In this study, no significant cognitive or
      behavioral changes occurred in patients treated with subthalamic stimulation when
      compared to patients receiving conventional medical treatment at 1 year follow
      up. Conclusions: Patients treated with LCIG may significantly improve some
      specific neuropsychological functions when compared with patients receiving STN
      DBS and with patients receiving conventional medical treatment after 1 year from
      the intervention; there are not significant cognitive or behavioral changes in
      patients treated with STN-DBS when compared to PD patients receiving conventional
      medical treatment after 1 year from the intervention. The outcomes showed in the
      study can help to the selection of the appropriate candidates for STN-DBS and
      LCIG.

PMID- 29201550
TI  - Dehydration is a strong predictor of long-term prognosis of thrombolysed patients
      with acute ischemic stroke.
AB  - Background and Purpose: Dehydration was found to be involved in the poor
      prognosis of patients with acute ischemic stroke. It is unclear whether
      dehydration status before onset is related with prognosis of thrombolysed
      patients with acute ischemic stroke. If it is the case, quickly hydrating may
      improve the prognosis. The present study was designed to explore the issue.
      Methods: Eligible 294 patients with acute ischemic stroke after thrombolysis were
      enrolled in the present study according to inclusion/exclusion criteria.
      According to the modified Rankin scale (mRS) 90 days post stroke, the patients
      were divided into two groups: mRS 0-2 (n = 191) and mRS 3-6 (n = 103). In the
      present study, BUN/Cr >= 15 combined with USG > 1.010 or either of them were
      chosen as dehydration marker. Clinical data were analyzed between two groups.
      Univariate and multivariate statistical analyses were carried out. Results: Age,
      fibrinogen, blood glucose, BUN/Cr, NIHSS score at admission, the systolic blood
      pressure (SBP) before thrombolysis, dehydration status (BUN/Cr >= 15 plus USG >
      1.010), hyperlipidemia, USG and D-dimer on admission day, and TOAST
      classification showed significant difference between two groups (p < .05).
      Further stratification analysis showed that BUN/Cr >= 15, NIHSS >= 6, blood
      glucose >=8, and SBP > 150 were markedly associated with poor outcome (mRS 3-6, p
      < .05). After adjusting for age, fibrinogen, USG, D-dimer, dehydration status,
      NIHSS, blood glucose, SBP, hyperlipidemia, and BUN/Cr at admission, multivariate
      logistic regression showed that dehydration status, higher NIHSS, higher blood
      glucose, and higher SBP at admission were independent risk factors for predicting
      the long-term poor prognosis of thrombolysed patients. Conclusions: The present
      findings suggest that BUN/Cr >= 15 combined with USG > 1.010 as a marker of
      dehydration status was an independent risk factor for long-term poor prognosis of
      thrombolysed patients with acute ischemic stroke.

PMID- 29201551
TI  - Investigation of the COMT Val158Met variant association with age of onset of
      psychosis, adjusting for cannabis use.
AB  - Objective: COMT rs4680 (Val158Met) genotype moderates the effect of cannabis on
      the age of onset of psychosis (AoP). We investigated the association between
      rs4680 and AoP, after adjusting for relevant covariates, in a Canadian Caucasian
      sample. Methods: One hundred and sixty-nine subjects with psychosis were
      recruited. AoP, defined as age of DSM-IV diagnosis was established using the
      Structured Clinical Interview for DSM-IV. Cannabis use data were collected using
      a self-report computerized questionnaire. DNA was extracted from saliva and
      genotyping of the COMT Val158Met polymorphism was done by SNaPshot and TaqMan
      assays. Logistic regression and Kaplan-Meier analysis results are reported.
      Results: In those who had used cannabis before 20 years of age, rs4680 had a
      trend level effect on AoP (median AoP: Val/Val < Val/Met < Met/Met 19.37, 20.95,
      21.24 years, respectively; log-rank test p = .051). Conclusion: Our data are
      indicative of the need to further investigate the association between the COMT
      rs4680 variant and AoP in the context of adolescent cannabis use.

PMID- 29201552
TI  - ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR.
AB  - Background: Dyslexia is a specific learning disorder affecting reading and
      spelling abilities. Its prevalence is ~5% in German-speaking individuals.
      Although the etiology of dyslexia largely remains to be determined, comprehensive
      evidence supports deficient phonological processing as a major contributing
      factor. An important prerequisite for phonological processing is auditory
      discrimination and, thus, essential for acquiring reading and spelling skills.
      The event-related potential Mismatch Response (MMR) is an indicator for auditory
      discrimination capabilities with dyslexics showing an altered late component of
      MMR in response to auditory input. Methods: In this study, we comprehensively
      analyzed associations of dyslexia-specific late MMRs with genetic variants
      previously reported to be associated with dyslexia-related phenotypes in multiple
      studies comprising 25 independent single-nucleotide polymorphisms (SNPs) within
      10 genes. Results: First, we demonstrated validity of these SNPs for dyslexia in
      our sample by showing that additional inclusion of a polygenic risk score
      improved prediction of impaired writing compared with a model that used MMR
      alone. Secondly, a multifactorial regression analysis was conducted to uncover
      the subset of the 25 SNPs that is associated with the dyslexia-specific late
      component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were
      found to be associated with MMR stronger than expected from multiple testing. To
      explore potential pathomechanisms, we annotated these variants with functional
      data including tissue-specific expression analysis and eQTLs. Conclusion: Our
      findings corroborate the late component of MMR as a potential endophenotype for
      dyslexia and support tripartite relationships between dyslexia-related SNPs, the
      late component of MMR and dyslexia.

PMID- 29201553
TI  - Proinflammatory cytokines correlate with early exercise attenuating anxiety-like
      behavior after cerebral ischemia.
AB  - Background and Objective: Stroke may cause neuropsychiatric problems, which have
      negative effects on cognitive functions and behavior. Exercise plays an important
      role in reducing the occurrence and development of stroke, the concrete mechanism
      is not fully clarified. In this study, we attempted to determine whether early
      treadmill exercise attenuates anxiety-like behavior by regulation of inflammation
      after brain ischemia. Method: We subjected adult male rats to middle cerebral
      artery occlusion (MCAO) for 90 min and trained rats started to run on a treadmill
      from postoperative day 1 to day 14. The effects of treadmill on cognitive
      functions, anxiety-like behavior, and immune activation were analyzed by Morris
      water maze test, open field test, elevated plus maze test, and enzyme-linked
      immunosorbent assay. Results: Early treadmill exercise significantly improved
      cognitive function, alleviated anxiety-like behavior in ischemic rats model; this
      improvement was associated with significantly decreased activation of astrocytes
      and microglia cells and proinflammatory markers (platelet-activating factor
      [PAF], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-alpha],
      intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1
      [VCAM-1]). Conclusion: Our results indicated that early treadmill exercise
      attenuated anxiety-like behavior by decreasing inflammation response, exercise
      conferred a great benefit of attenuating anxiety-like behavior via anti
      inflammatory treatment may prove to be a novel neuroprotective strategy for
      stroke.

PMID- 29201554
TI  - Linking Y-chromosomal short tandem repeat loci to human male impulsive
      aggression.
AB  - Introduction: Men are more susceptible to impulsive behavior than women.
      Epidemiological studies revealed that the impulsive aggressive behavior is
      affected by genetic factors, and the male-specific Y chromosome plays an
      important role in this behavior. In this study, we investigated the association
      between the impulsive aggressive behavior and Y-chromosomal short tandem repeats
      (Y-STRs) loci. Methods: The collected biologic samples from 271 offenders with
      impulsive aggressive behavior and 492 healthy individuals without impulsive
      aggressive behavior were amplified by PowerPlexRY23 PCR System and the resultant
      products were separated by electrophoresis and further genotyped. Then,
      comparisons in allele and haplotype frequencies of the selected 22 Y-STRs were
      made in the two groups. Results: Our results showed that there were significant
      differences in allele frequencies at DYS448 and DYS456 between offenders and
      controls (p < .05). Univariate analysis further revealed significant frequency
      differences for alleles 18 and 22 at DYS448 (0.18 vs 0.27, compared to the
      controls, p = .003, OR=0.57,95% CI=0.39-0.82; 0.03 vs 0.01, compared to the
      controls, p = .003, OR=7.45, 95% CI=1.57-35.35, respectively) and for allele 17
      at DYS456 (0.07 vs 0.14, compared to the controls, p = .006, OR=0.48, 95% CI
      =0.28-0.82) between two groups. Interestingly, the frequency of haploid haplotype
      22-15 on the DYS448-DYS456 (DYS448-DYS456-22-15) was significantly higher in
      offenders than in controls (0.033 vs 0.004, compared to the control, p = .001, OR
      = 8.42, 95%CI =1.81-39.24). Moreover, there were no significant differences in
      allele frequencies of other Y-STRs loci between two groups. Furthermore, the
      unconditional logistic regression analysis confirmed that alleles 18 and 22 at
      DYS448 and allele 17 at DYS456 are associated with male impulsive aggression.
      However, the DYS448-DYS456-22-15 is less related to impulsive aggression.
      Conclusion: Our results suggest a link between Y-chromosomal allele types and
      male impulsive aggression.

PMID- 29201555
TI  - Background and distribution of lobar microbleeds in cognitive dysfunction.
AB  - Objectives: Cerebral microbleeds (CMBs) are often observed in memory clinic
      patients. It has been generally accepted that deep CMBs (D-CMBs) result from
      hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL-CMBs) result from
      cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's
      disease (AD). Mixed CMBs (M-CMBs) have been partially attributed to HV and also
      partially attributed to CAA. The aim of this study was to elucidate the
      differences between SL-CMBs and M-CMBs in terms of clinical features and regional
      distribution. Materials: We examined 176 sequential patients in our memory clinic
      for clinical features and CMB location using susceptibility-weighted images
      obtained on a 3T-MRI. The number of lobar CMBs in SL-CMBs and M-CMBs was counted
      in each cerebral lobe and their regional density was adjusted according to the
      volume of each lobe. Results: Of the total 176 patients, 111 patients (63.1%) had
      CMBs. Within the patients who had CMBs, M-CMBs were found in 54 patients (48.6%),
      followed by SL-CMBs in 35 (31.5%) and D-CMBs in 19 (17.1%). The SL-CMB group
      showed a significantly higher prevalence of family history of dementia, whereas
      the M-CMB group showed an increasing trend toward hypertension and smoking. The
      prevalence of AD was significantly higher in the SL-CMBs group, whereas the
      prevalence of AD with cerebrovascular disease was higher in the M-CMBs group. The
      regional density of lobar CMBs was significantly higher in the occipital lobe in
      the M-CMB group, whereas the SL-CMB group showed higher regional density between
      regions an increasing tendency in the parietal and occipital lobe. Conclusion:
      The between-group differences in clinical features and regional distribution
      indicate there to be an etiological relationship of SL-CMBs to AD and CAA, and M
      CMBs to both HV and CAA.

PMID- 29201556
TI  - NS-Pten knockout mice show sex- and age-specific differences in ultrasonic
      vocalizations.
AB  - Objective: The goal of this study was to identify changes in quantitative and
      qualitative aspects of neonatal ultrasonic vocalizations USVs in neuron-subset
      specific (NS-Pten) knockout males and females when compared with wild-type male
      and female mice. Background: One signaling cascade that plays a crucial role in
      the development of an autistic-like phenotype is the PI3K/Akt/mTOR pathway. Mouse
      models that illustrate this connection include Fmr1, Tsc1, and NS-Pten-deficient
      mice. While numerous studies have investigated ultrasonic vocalizations in Fmr1
      knockout and Tsc1 heterogenous mice, none have investigated USVs in NS-Pten
      knockout mice using a full spectrum recording system. Methods: We recorded
      ultrasonic vocalizations from NS-Pten wild-type and knockout male and female mice
      on postnatal days 8 and 11. On these days, we measured the number and quality of
      calls emitted from pups when they were removed from their mothers. Results: We
      found that knockout pups emitted fewer vocalizations for both sexes (p < .05).
      Knockout males had calls of a shorter duration and lower peak amplitude on day 8,
      while showing a shorter duration, lower peak amplitude, and higher peak and
      fundamental frequency on day 11 (p < .001). Knockout females vocalized at a lower
      peak amplitude and fundamental frequency, and a higher peak frequency on day 8,
      while showing a shorter duration and a higher peak and fundamental frequency on
      day 11 (p < .001). Spectrographic analyses also revealed significant differences
      in call type for both genotypes and sexes (p < .05). Conclusions: These findings
      demonstrate that deletion of NS-Pten results in significant decreases in
      vocalizations across both sexes. Additionally, our findings indicate that the
      aberrant vocalizations and increased call duration seen in other mTOR models are
      also present in NS-Pten knockout mice. Our study provides evidence of a
      connection between hyperactive mTOR signaling and neonatal ultrasonic
      vocalizations.

PMID- 29201557
TI  - Brain lesions affecting gait recovery in stroke patients.
AB  - Objectives: Gait recovery is an important goal in stroke patients. Several
      studies have sought to uncover relationships between specific brain lesions and
      the recovery of gait, but the effects of specific brain lesions on gait remain
      unclear. Thus, we investigated the effects of stroke lesions on gait recovery in
      stroke patients. Materials and Methods: In total, 30 subjects with stroke were
      assessed in a retrograde longitudinal observational study. To assess gait
      function, the functional ambulation category (FAC) was tested four times:
      initially (within 2 weeks) and 1, 3, and 6 months after the onset of the stroke.
      Brain lesions were analyzed via overlap, subtraction, and voxel-based lesion
      symptom mapping (VLSM). Results: Ambulation with FAC improved significantly with
      time. Subtraction analysis showed that involvement of the corona radiata,
      internal capsule, globus pallidus, and putamen were associated with poor recovery
      of gait throughout 6 months after onset. The caudate nucleus did influence poor
      recovery of gait at 6 months after onset. VLSM revealed that corona radiata,
      internal capsule, globus pallidus, putamen and cingulum were related with poor
      recovery of gait at 3 months after onset. Corona radiata, internal capsule,
      globus pallidus, putamen, primary motor cortex, and caudate nucleus were related
      with poor recovery of gait at 6 months after onset. Conclusion: Results
      identified several important brain lesions for gait recovery in patients with
      stroke. These results may be useful for planning rehabilitation strategies for
      gait and understanding the prognosis of gait in stroke patients.

PMID- 29201558
TI  - Human Genomics of Mycobacterium tuberculosis Infection and Disease.
AB  - Purpose of review: The study of the genetic basis of tuberculosis pathogenesis
      has benefited from powerful technological innovations, a more structured
      definition of latent and clinical manifestations of the disease, and the
      application of functional genomics approaches. This short review aims to
      summarize recent advances and to provide a link with results of previous human
      genetic studies of tuberculosis susceptibility. Recent findings: Transcriptomics
      has been shown to be a useful tool to predict progression from latency to
      clinical disease while functional genomics has traced the molecular events that
      link pathogen-triggered gene expression and host genetics. Resistance to
      infection with Mycobacterium tuberculosis has been revealed to be strongly
      impacted by host genetics. Host genomics of clinical disease has been shown to be
      most powerful when focusing on carefully selected clinical entities and possibly
      by considering host pathogen combinations. Summary: Future studies need to build
      on the latest molecular findings to define disease subtypes to successfully
      elucidate the human genetic component in tuberculosis pathogenesis.

PMID- 29201560
TI  - DNA barcoding reveals the mislabeling of fish in a popular tourist destination in
      Brazil.
AB  - The consumption of raw fish has increased considerably in the West, since it is
      said to be potentially healthier than processed fish (for containing omega 3 and
      6, essential amino acids and vitamins). However this potential benefit, as well
      as the taste, value and even the risk of extinction are not the same for all
      species of fish, constituting grounds for fraud. Using the principles of the DNA
      barcode we revealed mislabelling of fish in Japanese restaurants and fishmarkets
      in Florianopolis, a popular tourist capital in Brazil. We sequenced the COI gene
      of 65 samples from fisheries and 80 from restaurants and diagnosed 30% of
      mislabeled samples in fisheries and 26% in restaurants. We discussed that frauds
      may have occurred for different reasons: to circumvent surveillance on threatened
      species; to sell fish with sizes smaller than allowed or abundant species as
      being a much rarer species (law of supply); to induce product consumption using
      species with better taste. It should be noted that some substitutions are derived
      from incorrect identification and are not a fraud per se; they are due to
      confusion of popular names or misunderstanding by the sellers. Therefore, we
      suggest the implementation of a systematic regulatory program conducted by
      governmental agencies to reduce mislabelling in order to avoid further damage to
      the community (in health and financial issues) and fish stocks.

PMID- 29201559
TI  - Genomic characterization of a new endophytic Streptomyces kebangsaanensis
      identifies biosynthetic pathway gene clusters for novel phenazine antibiotic
      production.
AB  - Background: Streptomyces are well known for their capability to produce many
      bioactive secondary metabolites with medical and industrial importance. Here we
      report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy)
      carbonyl) phenazine-1-carboxylic acid (HCPCA) extracted from Streptomyces
      kebangsaanensis, an endophyte isolated from the ethnomedicinal Portulaca
      oleracea. Methods: The HCPCA chemical structure was determined using nuclear
      magnetic resonance spectroscopy. We conducted whole genome sequencing for the
      identification of the gene cluster(s) believed to be responsible for phenazine
      biosynthesis in order to map its corresponding pathway, in addition to
      bioinformatics analysis to assess the potential of S. kebangsaanensis in
      producing other useful secondary metabolites. Results: The S. kebangsaanensis
      genome comprises an 8,328,719 bp linear chromosome with high GC content (71.35%)
      consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We
      identified 24 gene clusters involved in polyketide, nonribosomal peptide,
      terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster
      predicted to be responsible for phenazine biosynthesis. Discussion: The HCPCA
      phenazine structure was hypothesized to derive from the combination of two
      biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2
      diol, originated from the shikimic acid pathway. The identification of a
      biosynthesis pathway gene cluster for phenazine antibiotics might facilitate
      future genetic engineering design of new synthetic phenazine antibiotics.
      Additionally, these findings confirm the potential of S. kebangsaanensis for
      producing various antibiotics and secondary metabolites.

PMID- 29201561
TI  - Phylogeographic and population insights of the Asian common toad (Bufo
      gargarizans) in Korea and China: population isolation and expansions as response
      to the ice ages.
AB  - The effects of ice ages on speciation have been well documented for many European
      and North American taxa. In contrast, very few studies have addressed the
      consequences of such environmental and topographical changes in North East Asian
      species. More precisely, the Korean Peninsula offers a unique model to assess
      patterns and processes of speciation as it hosts the northern- and eastern-most
      distribution limit of some widespread Asian taxa. Despite this, studies
      addressing phylogeographic patterns and population genetics in the peninsula and
      surrounding countries are few and studies for most families are lacking. Here we
      inferred the phylogenetic relationships of the common toad (Bufo gargarizans)
      from South Korea and their North East Asian counterpart populations, based on
      mitochondrial data. Korean B. gargarizans GenBank BLASTs matched few individuals
      from nearby China, but the presence of a Korean clade suggests isolation on the
      Korean Peninsula, previous to the last glacial maximum, linked to sea level
      resurgence. Molecular clock calibrations within this group were used to date the
      divergence between clades and their relationship to paleo-climatic events in the
      area. Lack of genetic structure among South Korean populations and strong
      homogeneity between the Korean and some Chinese localities suggest weak isolation
      and recent expansion. Geographical projection of continuous coalescent maximum
      clade-credibility trees shows an original Chinese expansion towards the Korean
      Peninsula through the Yellow Sea circa two million years ago with colonisation
      events dating circa 800 thousand years ago (K. y. a.). Following this
      colonisation, the data point to outgoing Korean Peninsula dispersal events
      throughout different periods, towards the North through land, and West through
      land bridge formations over the Yellow Sea during sea level falls. In accordance,
      demographic analyses revealed a population expansion in the Koran Peninsula circa
      300 K. y. a., likely attributed to glacial cycle fluctuations.

PMID- 29201562
TI  - Evaluation of potential reference genes for real-time qPCR analysis in a
      biparental beetle, Lethrus apterus (Coleoptera: Geotrupidae).
AB  - Hormones play an important role in the regulation of physiological, developmental
      and behavioural processes. Many of these mechanisms in insects, however, are
      still not well understood. One way to investigate hormonal regulation is to
      analyse gene expression patterns of hormones and their receptors by real-time
      quantitative polymerase chain reaction (RT-qPCR). This method, however, requires
      stably expressed reference genes for normalisation. In the present study, we
      evaluated 11 candidate housekeeping genes as reference genes in samples of
      Lethrus apterus, an earth-boring beetle with biparental care, collected from a
      natural population. For identifying the most stable genes we used the following
      computational methods: geNorm, NormFinder, BestKeeper, comparative delta Ct
      method and RefFinder. Based on our results, the two body regions sampled (head
      and thorax) differ in which genes are most stably expressed. We identified two
      candidate reference genes for each region investigated: ribosomal protein L7A and
      RP18 in samples extracted from the head, and ribosomal protein L7A and RP4
      extracted from the muscles of the thorax. Additionally, L7A and RP18 appear to be
      the best reference genes for normalisation in all samples irrespective of body
      region. These reference genes can be used to study the hormonal regulation of
      reproduction and parental care in Lethrus apterus in the future.

PMID- 29201563
TI  - Facilitative and competitive interaction components among New England salt marsh
      plants.
AB  - Intra- and interspecific interactions can be broken down into facilitative and
      competitive components. The net interaction between two organisms is simply the
      sum of these counteracting elements. Disentangling the positive and negative
      components of species interactions is a critical step in advancing our
      understanding of how the interaction between organisms shift along physical and
      biotic gradients. We performed a manipulative field experiment to quantify the
      positive and negative components of the interactions between a perennial forb,
      Aster tenuifolius, and three dominant, matrix-forming grasses and rushes in a New
      England salt marsh. Specifically, we asked whether positive and negative
      interaction components: (1) are unique or redundant across three matrix-forming
      species (two grasses; Distichlis spicata and Spartina patens, and one rush;
      Juncus gerardi), and (2) change across Aster life stages (seedling, juvenile, and
      adult). For adult Aster the strength of the facilitative component of the matrix
      forb interaction was stronger than the competitive component for two of the three
      matrix species, leading to net positive interactions. There was no statistically
      significant variation among matrix species in their net or component effects. We
      found little difference in the effects of J. gerardi on Aster at later life
      history stages; interaction component strengths did not differ between juveniles
      and adults. However, mortality of seedlings in neighbor removal plots was 100%,
      indicating a particularly strong and critical facilitative effect of matrix
      species on this forb during the earliest life stages. Overall, our results
      indicate that matrix forming grasses and rushes have important, yet largely
      redundant, positive net effects on Aster performance across its life cycle.
      Studies that untangle various components of interactions and their contingencies
      are critical to both expanding our basic understanding of community organization,
      and predicting how natural communities and their component parts will respond to
      environmental change.

PMID- 29201564
TI  - An exceptionally preserved armored dinosaur reveals the morphology and allometry
      of osteoderms and their horny epidermal coverings.
AB  - Although the evolution and function of "exaggerated" bony projections in
      ornithischian dinosaurs has been subject to significant debate recently, our
      understanding of the structure and morphology of their epidermal keratinized
      coverings is greatly limited. The holotype of Borealopelta, a new nodosaurid
      ankylosaur, preserves osteoderms and extensive epidermal structures (dark organic
      residues), in anatomic position across the entire precaudal length. Contrasting
      previous specimens, organic epiosteodermal scales, often in the form of horn-like
      (keratinous) sheaths, cap and exaggerate nearly all osteoderms, allowing for
      morphometric and allometric analyses of both the bony osteoderms and their horny
      sheaths. A total of 172 osteoderms were quantified, with osteoderm spine length
      and height being positively allometric with respect to basal length and width.
      Despite tight correlations between the different measures amongst all other
      osteoderms, the large parascapular spines represent consistent outliers.
      Thickness and relative contribution of the keratinized epiosteodermal
      scales/sheaths varies greatly by region, ranging from 2% to 6% for posterior
      thoracics, to ~25% (1.3*) for the parascapular spines-similar to horn sheaths in
      some bovid analogues. Relative to the bony cores, the horny portions of the
      spines are strongly positively allometric (slope = 2.3, CI = 1.8-2.8). Strong
      allometric scaling, species-specific morphology, and significant keratinous
      extension of the cervicoscapular spines is consistent with elaboration under
      socio-sexual selection. This marks the first allometric analysis of ornithischian
      soft tissues.

PMID- 29201565
TI  - Age-based and reproductive biology of the Pacific Longnose Parrotfish Hipposcarus
      longiceps from Guam.
AB  - The Pacific longnose parrotfish Hipposcarus longiceps (Valenciennes 1840)
      represents a prime fishery resource throughout much of the tropical Pacific. In
      this study, we sampled the species from the Guam commercial fishery market across
      five consecutive years to characterize reproductive and age-based demographic
      information imperative for informed fishery management. Compared with other
      parrotfishes, this species was found to be large-bodied, but has only a moderate
      life span of 10 + years. Hipposcarus longiceps was confirmed as a diandric
      protogynous hermaphrodite with highly sex-specific growth patterns and an overall
      mean asymptotic length of 434 mm fork length (FL). Females were estimated to
      reach median maturity at 329 mm FL (2.4 years) and have a median length at female
      to-male sex change of 401 mm FL. Life-history trait values derived here were used
      to update previous models relating life history and vulnerability to
      overexploitation. We found that enhancement of just one species' trait values
      improved model fits considerably, which strengthens the conclusion that life
      history traits are a strong determinant of species' vulnerability in the
      parrotfishes. This information is an imperative complement to other data sources
      facilitating formal stock assessment of a key fishery target.

PMID- 29201566
TI  - The presence of genes encoding enzymes that digest carbohydrates in coral genomes
      and analysis of their activities.
AB  - Numerous enzymes that digest carbohydrates, such as cellulases and chitinases,
      are present in various organisms (e.g., termites, nematodes, and so on).
      Recently, the presence of cellulases and chitinases has been reported in marine
      organisms such as urchin and bivalves, and their several roles in marine
      ecosystems have been proposed. In this study, we reported the presence of genes
      predicted to encode proteins similar to cellulases and chitinases in the genome
      of the coral Acropora digitifera, their gene expression patterns at various life
      stages, and cellulose- and chitin-degrading enzyme activities in several coral
      species (A. digitifera, Galaxea fascicularis, Goniastrea aspera, Montipora
      digitata, Pavona divaricata, Pocillopora damicornis, and Porites australiensis).
      Our gene expression analysis demonstrated the expressions of these cellulase- and
      chitinase-like genes during various life stages, including unfertilized eggs,
      fertilized eggs, zygotes, planula larvae, primary polyps and adults of A.
      digitifera. Agar plate assays confirmed cellulase and chitinase activities in the
      tissues extracted from adult branches of several coral species. These results
      suggested that corals are able to utilize cellulases and chitinases in their life
      histories.

PMID- 29201567
TI  - The zebrafish as a model system for analyzing mammalian and native alpha
      crystallin promoter function.
AB  - Previous studies have used the zebrafish to investigate the biology of lens
      crystallin proteins and their roles in development and disease. However, little
      is known about zebrafish alpha-crystallin promoter function, how it compares to
      that of mammals, or whether mammalian alpha-crystallin promoter activity can be
      assessed using zebrafish embryos. We injected a variety of alpha-crystallin
      promoter fragments from each species combined with the coding sequence for green
      fluorescent protein (GFP) into zebrafish zygotes to determine the resulting
      spatiotemporal expression patterns in the developing embryo. We also measured
      mRNA levels and protein abundance for all three zebrafish alpha-crystallins. Our
      data showed that mouse and zebrafish alphaA-crystallin promoters generated
      similar GFP expression in the lens, but with earlier onset when using mouse
      promoters. Expression was also found in notochord and skeletal muscle in a
      smaller percentage of embryos. Mouse alphaB-crystallin promoter fragments drove
      GFP expression primarily in zebrafish skeletal muscle, with less common
      expression in notochord, lens, heart and in extraocular regions of the eye. A
      short fragment containing only a lens-specific enhancer region increased lens and
      notochord GFP expression while decreasing muscle expression, suggesting that the
      influence of mouse promoter control regions carries over into zebrafish embryos.
      The two paralogous zebrafish alphaB-crystallin promoters produced subtly
      different expression profiles, with the aBa promoter driving expression equally
      in notochord and skeletal muscle while the alphaBb promoter resulted primarily in
      skeletal muscle expression. Messenger RNA for zebrafish alphaA increased between
      1 and 2 days post fertilization (dpf), alphaBa increased between 4 and 5 dpf, but
      alphaBb remained at baseline levels through 5 dpf. Parallel reaction monitoring
      (PRM) mass spectrometry was used to detect alphaA, aBa, and alphaBb peptides in
      digests of zebrafish embryos. In whole embryos, alphaA-crystallin was first
      detected by 2 dpf, peaked in abundance by 4-5 dpf, and was localized to the eye.
      alphaBa was detected in whole embryo at nearly constant levels from 1-6 dpf, was
      also localized primarily to the eye, and its abundance in extraocular tissues
      decreased from 4-7 dpf. In contrast, due to its low abundance, no alphaBb protein
      could be detected in whole embryo, or dissected eye and extraocular tissues. Our
      results show that mammalian alpha-crystallin promoters can be efficiently
      screened in zebrafish embryos and that their controlling regions are well
      conserved. An ontogenetic shift in zebrafish aBa-crystallin promoter activity
      provides an interesting system for examining the evolution and control of tissue
      specificity. Future studies that combine these promoter based approaches with the
      expanding ability to engineer the zebrafish genome via techniques such as
      CRISPR/Cas9 will allow the manipulation of protein expression to test hypotheses
      about lens crystallin function and its relation to lens biology and disease.

PMID- 29201568
TI  - Diagnostic value of serum procalcitonin, lactate, and high-sensitivity C-reactive
      protein for predicting bacteremia in adult patients in the emergency department.
AB  - Background: Few studies compared the diagnostic value of procalcitonin with a
      combination of other tests including lactate and high-sensitivity C-reactive
      protein in the prediction of pathogenic bacteremia in emergency department adult
      patients. Methods: We performed a retrospective study assessing the differences
      in performances of procalcitonin at a cutoff of 0.5 ng/mL, lactate at a cutoff of
      19.8 mg/dL, high-sensitivity C-reactive protein at a cutoff of 0.8 mg/dL and
      their combinations for predicting bacteremia in emergency department adult
      patients. Sensitivity, specificity, overall accuracy, positive-test and negative
      test likelihood, and diagnostic odds ratio with 95% confidence interval for each
      test combination were calculated for comparison. The receiver operating
      characteristic curve for every single test were compared using DeLong's method.
      We also performed a sensitivity analysis in two expanded patient cohorts to
      assess the discriminative ability of procalcitonin or test combination. Results:
      A total of 886 patients formed the initial patient cohort. The area under the
      receiver operating characteristic curve for discriminating positive blood culture
      was: procalcitonin = 0.72 (95% CI [0.69-0.75]) with a derived optimal cutoff at
      3.9 ng/mL; lactate 0.69 (0.66-0.72) with an optimal cutoff at 17.9 mg/dL; high
      sensitivity C-reactive protein 0.56 (0.53-0.59) with an optimal cutoff of 13
      mg/dL; with pairwise comparisons showing statistically significant better
      performance of either procalcitonin or lactate outperforming high-sensitivity C
      reactive protein. To predict positive blood cultures, the diagnostic odds ratio
      for procalcitonin was 3.64 (95% CI [2.46-5.51]), lactate 2.93 (2.09-4.14), and
      high-sensitivity C-reactive protein 0.91 (0.55-1.55; P = 0.79). About combined
      tests, the diagnostic odds ratio for procalcitonin and lactate increases were
      3.98 (95% CI [2.81-5.63]) for positive blood culture prediction. Elevated
      procalcitonin level rendered a six-fold increased risk of positive gram-negative
      bacteremia with a diagnostic odds ratio of 6.44 (95% CI [3.65-12.15]), which
      showed no further improvement in any test combinations. In the sensitivity
      analysis, as a single test to predict unspecified, gram-negative and gram
      positive bacteremia, procalcitonin performed even better in an expanded cohort of
      2,234 adult patients in terms of the diagnostic odds ratio. Discussions: For
      adult emergency patients, procalcitonin has an acceptable discriminative ability
      for bacterial blood culture and a better discriminative ability for gram-negative
      bacteremia when compared with lactate and high-sensitivity C-reactive protein.
      High-sensitivity C-reactive protein at a cutoff of 0.8 mg/dL performed poorly for
      the prediction of positive bacterial culture.

PMID- 29201569
TI  - Denitrifying metabolism of the methylotrophic marine bacterium Methylophaga
      nitratireducenticrescens strain JAM1.
AB  - Background: Methylophaga nitratireducenticrescens strain JAM1 is a
      methylotrophic, marine bacterium that was isolated from a denitrification reactor
      treating a closed-circuit seawater aquarium. It can sustain growth under anoxic
      conditions by reducing nitrate ([Formula: see text]) to nitrite ([Formula: see
      text]). These physiological traits are attributed to gene clusters that encode
      two dissimilatory nitrate reductases (Nar). Strain JAM1 also contains gene
      clusters encoding two nitric oxide (NO) reductases and one nitrous oxide (N2O)
      reductase, suggesting that NO and N2O can be reduced by strain JAM1. Here we
      characterized further the denitrifying activities of M. nitratireducenticrescens
      JAM1. Methods: Series of oxic and anoxic cultures of strain JAM1 were performed
      with N2O, [Formula: see text] or sodium nitroprusside, and growth and N2O,
      [Formula: see text], [Formula: see text] and N2 concentrations were measured.
      Ammonium ([Formula: see text])-free cultures were also tested to assess the
      dynamics of N2O, [Formula: see text] and [Formula: see text]. Isotopic labeling
      of N2O was performed in 15NH4+-amended cultures. Cultures with the
      JAM1DeltanarG1narG2 double mutant were performed to assess the involvement of the
      Nar systems on N2O production. Finally, RT-qPCR was used to measure the gene
      expression levels of the denitrification genes cytochrome bc-type nitric oxide
      reductase (cnorB1 and cnorB2) and nitrous oxide reductase (nosZ), and also nnrS
      and norR that encode NO-sensitive regulators. Results: Strain JAM1 can reduce NO
      to N2O and N2O to N2 and can sustain growth under anoxic conditions by reducing
      N2O as the sole electron acceptor. Although strain JAM1 lacks a gene encoding a
      dissimilatory [Formula: see text] reductase, [Formula: see text]-amended cultures
      produce N2O, representing up to 6% of the N-input. [Formula: see text] was shown
      to be the key intermediate of this production process. Upregulation in the
      expression of cnorB1, cnorB2, nnrS and norR during the growth and the N2O
      accumulation phases suggests NO production in strain JAM1 cultures. Discussion:
      By showing that all the three denitrification reductases are active, this
      demonstrates that M. nitratireducenticrescens JAM1 is one of many bacteria
      species that maintain genes associated primarily with denitrification, but not
      necessarily related to the maintenance of the entire pathway. The reason to
      maintain such an incomplete pathway could be related to the specific role of
      strain JAM1 in the denitrifying biofilm of the denitrification reactor from which
      it originates. The production of N2O in strain JAM1 did not involve Nar, contrary
      to what was demonstrated in Escherichia coli. M. nitratireducenticrescens JAM1 is
      the only reported Methylophaga species that has the capacity to grow under anoxic
      conditions by using [Formula: see text] and N2O as sole electron acceptors for
      its growth. It is also one of a few marine methylotrophs that is studied at the
      physiological and genetic levels in relation to its capacity to perform
      denitrifying activities.

PMID- 29201570
TI  - Impacts of diarrhea on the immune system, intestinal environment, and expression
      of PGRPs in New Zealand rabbits.
AB  - Diarrhea is a syndrome of digestive disorders in young rabbits and may lead to
      secondary infections resulting in reduced immunity and higher mortality in baby
      rabbits, with serious impacts on rabbit farming. In this study, we investigated
      the effects of diarrhea on the health of baby rabbits in terms of intestinal
      mucosal development, immune function, and intestinal microbial diversity. We
      found that the duodenal villus length and the villus/crypt ratio in rabbits with
      diarrhea were significantly reduced compared with those in healthy rabbits (P <
      0.01). Rabbits with diarrhea had significantly lower concentrations of acetic
      acid (P < 0.05), higher pH levels (P < 0.05), and higher levels of ammonia
      nitrogen (P < 0.01) in the cecum. Moreover, diarrhea in baby rabbits led to
      significantly reduced levels of total serum protein (P < 0.05) and markedly
      increased levels of alkaline phosphatase, urea nitrogen, TNF-alpha, and IL-6 (P <
      0.05). Transcriptional analysis of peptidoglycan recognition proteins (PGRPs,
      including PGLYRP-1, PGLYRP-2, and PGLYRP-3) using real-time PCR revealed that
      diarrhea induced the upregulation of PGRPs in the cecum and duodenum.
      Furthermore, through pyrosequencing of the 16S rRNA V4 region in cecum samples,
      we found that the total number and diversity of microbes were not significantly
      different between healthy rabbits and those with diarrhea, though there were
      noticeable differences in the prevalences of Clostridium, Roseburia, and
      Alistipes. Our results will contribute to a better understanding of the
      pathological mechanisms of diarrhea in young rabbits.

PMID- 29201572
TI  - Geological duration of ammonoids controlled their geographical range of fossil
      distribution.
AB  - The latitudinal distributions in Devonian-Cretaceous ammonoids were analyzed at
      the genus level, and were compared with the hatchling sizes (i.e., ammonitella
      diameters) and the geological durations. The results show that (1) length of
      temporal ranges of ammonoids effected broader ranges of fossil distribution and
      paleobiogeography of ammonoids, and (2) the hatchling size was not related to the
      geographical range of fossil distribution of ammonoids. Reducing the influence of
      geological duration in this analysis implies that hatchling size was one of the
      controlling factors that determined the distribution of ammonoid habitats at any
      given period in time: ammonoids with smaller hatchling sizes tended to have
      broader ammonoid habitat ranges. These relationships were somewhat blurred in the
      Devonian, Carboniferous, Triassic, and Jurassic, which is possibly due to (1) the
      course of development of a reproductive strategy with smaller hatchling sizes in
      the Devonian and (2) the high origination rates after the mass extinction events.

PMID- 29201571
TI  - Transcriptomic profiling of mTOR and ryanodine receptor signaling molecules in
      developing zebrafish in the absence and presence of PCB 95.
AB  - The mechanistic target of rapamycin (mTOR) and ryanodine receptor (RyR) signaling
      pathways regulate fundamental processes of neurodevelopment, and genetic
      mutations within these pathways have been linked to neurodevelopmental disorders.
      While previous studies have established that these signaling molecules are
      expressed in developing zebrafish, a detailed characterization of the ontogenetic
      profile of these signaling molecules is lacking. Thus, we evaluated the
      spatiotemporal expression of key transcripts in mTOR and RyR signaling pathways
      in wildtype zebrafish at 24, 72 and 120 hours post fertilization (hpf). We
      further determined whether transcriptional profiles of a subset of genes in both
      pathways were altered by exposure to PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a
      pervasive environmental contaminant known to cause developmental neurotoxicity in
      mammalian systems via RyR-dependent mechanisms. Quantitative PCR revealed that
      transcription generally increased across development. Genes in the signaling
      pathway upstream of the mTORC1 complex, and the RyR-paralogs, ryr2a and ryr3,
      were robustly upregulated, and in situ hybridization of ryr3 coincided with a
      transcriptional shift from muscle to neuronal tissue after 24 hpf. Static
      waterborne exposure to PCB 95 beginning at 6 hpf significantly altered
      transcription of genes in both pathways. These changes were concentration- and
      time-dependent, and included downregulation of rptor, a member of the mTORC1
      complex, at both 72 and 120 hpf, and increased transcript levels of the RyR
      paralog ryr2b and downstream target of RyR signaling, Wingless-type 2ba (wnt2ba)
      at 72 hpf. The detailed transcriptomic profiling of key genes within these two
      signaling pathways provides a baseline for identifying other environmental
      factors that modify normal spatiotemporal expression patterns of mTOR and RyR
      signaling pathways in the developing zebrafish, as illustrated here for PCB 95.

PMID- 29201573
TI  - On the relationship between tumour growth rate and survival in non-small cell
      lung cancer.
AB  - A recurrent question within oncology drug development is predicting phase III
      outcome for a new treatment using early clinical data. One approach to tackle
      this problem has been to derive metrics from mathematical models that describe
      tumour size dynamics termed re-growth rate and time to tumour re-growth. They
      have shown to be strong predictors of overall survival in numerous studies but
      there is debate about how these metrics are derived and if they are more
      predictive than empirical end-points. This work explores the issues raised in
      using model-derived metric as predictors for survival analyses. Re-growth rate
      and time to tumour re-growth were calculated for three large clinical studies by
      forward and reverse alignment. The latter involves re-aligning patients to their
      time of progression. Hence, it accounts for the time taken to estimate re-growth
      rate and time to tumour re-growth but also assesses if these predictors correlate
      to survival from the time of progression. I found that neither re-growth rate nor
      time to tumour re-growth correlated to survival using reverse alignment. This
      suggests that the dynamics of tumours up until disease progression has no
      relationship to survival post progression. For prediction of a phase III trial I
      found the metrics performed no better than empirical end-points. These results
      highlight that care must be taken when relating dynamics of tumour imaging to
      survival and that bench-marking new approaches to existing ones is essential.

PMID- 29201574
TI  - Penetrating Orbital Injuries: A Review.
AB  - Penetrating injuries to the orbit represent a small but very complicated portion
      of head injuries. Because of the close proximity to many vital structures, any
      penetrating orbital injury requires a multidisciplinary follow-up. Cases of
      penetrating injuries have flooded the literature, but no one has presented a
      systematic approach to the complications associated with these types of injuries.
      Herein, we present the complications associated with each orbital entry mode:
      superior, inferior, medial, lateral rims of the orbit, and extraorbital entry.

PMID- 29201576
TI  - Anatomical Study of the Zygomaticotemporal Branch Inside the Orbit.
AB  - The location of the opening of the zygomaticotemporal branch (ZTb) of the
      zygomatic nerve inside the orbit (ZTFIN) has significant surgical implications.
      This study was conducted to locate the ZTFIN and investigate the variations of
      the ZTb inside the orbit. A total of 20 sides from 10 fresh frozen cadaveric
      Caucasian heads were used in this study. The vertical distance between the
      inferior margin of the orbit and ZTFIN (V-ZTFIN), the horizontal distance between
      the lateral margin of the orbit and ZTFIN (H-ZTFIN), and the diameter of the
      ZTFIN (D-ZTFIN) were measured. The patterns of the ZTb inside the orbit were
      classified into five different groups: both ZTb and LN innervating the lacrimal
      gland independently (Group A), both ZTb and LN innervating the lacrimal gland
      with a communicating branch (Group B), ZTb joining the LN without a branch to the
      lacrimal gland (Group C), the ZTb going outside the orbit through ZTFIN without a
      branch to the lacrimal gland nor LN (Group D), and absence of the ZTb (Group E).
      The D-ZTFIN V-ZTFIN H-ZTFIN ranged from 0.2 to 1.1 mm, 6.6 to 21.5 mm, 2.0 to
      11.3 mm, respectively. The number of sides in Groups A, B, C, D, and E were 13
      sides (65%), three sides (15%), none (0%), two sides (10%), and two sides (10%),
      respectively. Such anatomical knowledge might reduce complications following
      surgery in and around the ZTb.

PMID- 29201575
TI  - Clinical and Echocardiographic Follow-up after Successful Percutaneous
      Transvenous Mitral Commissurotomy.
AB  - Background The objective of the study was to determine the long-term outcomes,
      including mitral restenosis and regurgitation, after successful percutaneous
      transvenous mitral commissurotomy (PTMC). Methods This cross-sectional
      prospective study was conducted at the cardiology department of Lady Reading
      Hospital, Peshawar, Pakistan, from January 2007 to December 2009. A total of 84
      patients were followed up for a period of 96 months. Pre and post percutaneous
      transvenous mitral commissurotomy echocardiography was done on the mitral valve
      area (MVA) using two-dimensional (2D) and color doppler echocardiography.
      Patients who had successful PTMC were followed up for MVA loss, mitral
      regurgitation (MR), and cardiac death. SPSS Software (IBM SPSS Statistics for
      Windows, Version 22.0, Armonk, NY: IBM Corp.; 2013) was used for data analysis.
      Results Of the 84 patients, 21 were male, and 63 were females. The mean age was
      35 +/- 11 years. After PTMC, the mean valve two-dimensional area increased from
      0.84 +/- 0.13 to 1.83 +/- 0.49 cm2 (p value <0.001). MR was mild in 49 patients
      (62.8%), moderate in 27 patients (34.6%), and severe in two patients (2.6%). Good
      results were achieved in 60 (71.4%). Patients with good results were younger (24
      +/- 4), and had a relatively lower Wilkin's score, with a mean value of (8.4 +/-
      2.8). Follow-up events were death in six patients, mitral valve replacement (MVR)
      in 10 patients, and restenosis in seven patients. The Kaplan-Meier curve was used
      for the follow-up end points. Patient who required PTMC for mitral restenosis
      survived for a longer time than those requiring MVR, and those who had cardiac
      death due to severe pulmonary hypertension or heart failure. Conclusion Patients
      who had favorable Wilkin's score and underwent PTMC for severe symptomatic mitral
      stenosis had better event-free survival in the long term follow-up.

PMID- 29201577
TI  - Orbital Blowout Fracture with Complete Dislocation of the Globe into the
      Maxillary Sinus.
AB  - This rare case report describes the diagnosis and treatment of an isolated left
      sided orbital floor fracture with a complete dislocation of the globe into the
      maxillary sinus and briefly discusses the indications of surgery and recovery for
      orbital floor fractures in general. Complete herniation of the globe through an
      orbital blow-out fracture is uncommon. However, the current case illustrates that
      such an occurrence should be in the differential diagnosis and should be
      considered, especially following high speed/impact injuries involving a foreign
      object. In these rare cases, surgical intervention is required.

PMID- 29201578
TI  - Vertebral Compression Fractures after Lumbar Instrumentation.
AB  - Lumbar spinal stenosis (LSS) is primarily found in an older population. This is a
      similar demographic group that develops both osteoporosis and vertebral
      compression fractures (VCF). This report reviewed a series of patients treated
      for VCF that had previous lumbar surgery for symptomatic spinal stenosis.
      Patients that only underwent laminectomy or fusion without instrumentation had a
      similar distribution of VCF as the non-surgical population in the mid-thoracic,
      or lower thoracic and upper lumbar spine. However, in the patients that had
      previous short-segment spinal instrumentation, fractures were found to be located
      more commonly in the mid-lumbar spine or sacrum adjacent to or within one or two
      spinal segments of the spinal instrumentation. Adjacent-level fractures that
      occur due to vertebral osteoporosis after long spinal segment instrumentation has
      been discussed in the literature. The purpose of this report is to highlight the
      previously unreported finding of frequent lumbar and sacral osteoporotic
      fractures in post-lumbar instrumentation surgery patients. Important additional
      factors found were lack of preventative medical treatment for osteoporosis, and
      secondary effects related to inactivity, especially during the first year after
      surgery.

PMID- 29201579
TI  - Overtube-Assisted Foreign Body Removal: A Review of Endoscopic Management and
      Case Illustration.
AB  - The ingestion of foreign bodies is a common medical emergency seen in both adults
      and children. In children, the most commonly ingested foreign bodies include
      coins, toys, magnets, and batteries. In adults, food bolus impaction represents
      the most common cause of foreign body ingestion. The majority of foreign bodies
      pass spontaneously. Sharp or pointed objects increase the risk of perforation.
      Emergent endoscopic intervention is indicated in cases of esophageal obstruction,
      ingestion of disk batteries, and sharp pointed objects in the esophagus. Flexible
      endoscopy is the therapeutic method of choice for removing foreign bodies. It is
      preferred due to its high success rate and low risk for complications.
      Additionally, the use of an overtube provides gastric and esophageal protection
      from mucosal laceration. We present a 27-year-old male who ingested six razor
      blades and a curtain hook and review endoscopic management.

PMID- 29201580
TI  - Multimodality 3D Superposition and Automated Whole Brain Tractography:
      Comprehensive Printing of the Functional Brain.
AB  - Whole brain tractography using diffusion tensor imaging (DTI) sequences can be
      used to map cerebral connectivity; however, this can be time-consuming due to the
      manual component of image manipulation required, calling for the need for a
      standardized, automated, and accurate fiber tracking protocol with automatic
      whole brain tractography (AWBT). Interpreting conventional two-dimensional (2D)
      images, such as computed tomography (CT) and magnetic resonance imaging (MRI), as
      an intraoperative three-dimensional (3D) environment is a difficult task with
      recognized inter-operator variability. Three-dimensional printing in neurosurgery
      has gained significant traction in the past decade, and as software, equipment,
      and practices become more refined, trainee education, surgical skills, research
      endeavors, innovation, patient education, and outcomes via valued care is
      projected to improve. We describe a novel multimodality 3D superposition (MMTS)
      technique, which fuses multiple imaging sequences alongside cerebral tractography
      into one patient-specific 3D printed model. Inferences on cost and improved
      outcomes fueled by encouraging patient engagement are explored.

PMID- 29201581
TI  - Contrast Enhancement of Aneurysm Sac Post-Pipeline Treatment Interpreted as
      Recanalization.
AB  - Multiple imaging modalities are available to evaluate aneurysms post-flow
      diverter (FD) placement. Though digital subtraction angiography (DSA) is the gold
      standard imaging modality post-FD placement, it is not perfect, and neither are
      other techniques, including contrast-enhanced magnetic resonance angiography (CE
      MRA) and magnetic resonance imaging (MRI). We present a case of a 73-year-old
      woman with a right internal carotid artery (ICA) aneurysm treated with a pipeline
      embolization device (PED). Initial follow-up post-PED placement by three
      dimensional time-of-flight (3D-TOF) MRA demonstrated aneurysm occlusion, which
      was confirmed by computed tomography angiography (CTA) and CE-MRA in subsequent
      follow-up appointments. However, repeat CE-MRA two years later suggested
      recanalization of the aneurysm. After discussion with neuroradiologists and
      follow-up with a dynamic MRA, this finding was determined to be false. These
      findings shed light on the potential pitfall of using CE-MRA alone or any single
      imaging modality in the assessment of aneurysms post-PED placement. Our case
      report explores various imaging modalities used in the assessment of aneurysms
      post-PED placement and highlights the need to use multiple techniques for an
      accurate assessment.

PMID- 29201582
TI  - Dissolved organic carbon fluxes in the Middle Atlantic Bight: An integrated
      approach based on satellite data and ocean model products.
AB  - Continental margins play an important role in global carbon cycle, accounting for
      15-21% of the global marine primary production. Since carbon fluxes across
      continental margins from land to the open ocean are not well constrained, we
      undertook a study to develop satellite algorithms to retrieve dissolved organic
      carbon (DOC) and combined these satellite data with physical circulation model
      products to quantify the shelf boundary fluxes of DOC for the U.S. Middle
      Atlantic Bight (MAB). Satellite DOC was computed through seasonal relationships
      of DOC with colored dissolved organic matter absorption coefficients, which were
      derived from an extensive set of in situ measurements. The multiyear time series
      of satellite-derived DOC stocks (4.9 Teragrams C; Tg) shows that freshwater
      discharge influences the magnitude and seasonal variability of DOC on the
      continental shelf. For the 2010-2012 period studied, the average total estuarine
      export of DOC into the MAB shelf is 0.77 Tg C yr-1 (year). The integrated DOC
      tracer fluxes across the shelf boundaries are 12.1 Tg C yr-1 entering the MAB
      from the southwest alongshore boundary, 18.5 Tg C yr-1 entering the MAB from the
      northeast alongshore boundary, and 29.0 Tg C yr-1 flowing out of the MAB across
      the entire length of the 100 m isobath. The magnitude of the cross-shelf DOC flux
      is quite variable in time (monthly) and space (north to south). The highly
      dynamic exchange of water along the shelf boundaries regulates the DOC budget of
      the MAB at subseasonal time scales.

PMID- 29201583
TI  - Spectral slopes of the absorption coefficient of colored dissolved and detrital
      material inverted from UV-visible remote sensing reflectance.
AB  - The spectral slope of the absorption coefficient of colored dissolved and
      detrital material (CDM), Scdm (units: nm-1), is an important optical parameter
      for characterizing the absorption spectral shape of CDM. Although highly variable
      in natural waters, in most remote sensing algorithms, this slope is either kept
      as a constant or empirically modeled with multiband ocean color in the visible
      domain. In this study, we explore the potential of semianalytically retrieving
      Scdm with added ocean color information in the ultraviolet (UV) range between 360
      and 400 nm. Unique features of hyperspectral remote sensing reflectance in the UV
      visible wavelengths (360-500 nm) have been observed in various waters across a
      range of coastal and open ocean environments. Our data and analyses indicate that
      ocean color in the UV domain is particularly sensitive to the variation of the
      CDM spectral slope. Here, we used a synthesized data set to show that adding UV
      wavelengths to the ocean color measurements will improve the retrieval of Scdm
      from remote sensing reflectance considerably, while the spectral band settings of
      past and current satellite ocean color sensors cannot fully account for the
      spectral variation of remote sensing reflectance. Results of this effort support
      the concept to include UV wavelengths in the next generation of satellite ocean
      color sensors.

PMID- 29201584
TI  - The warmer the ocean surface, the shallower the mixed layer. How much of this is
      true?
AB  - Ocean surface warming is commonly associated with a more stratified, less
      productive, and less oxygenated ocean. Such an assertion is mainly based on
      consistent projections of increased near-surface stratification and shallower
      mixed layers under global warming scenarios. However, while the observed sea
      surface temperature (SST) is rising at midlatitudes, the concurrent ocean record
      shows that stratification is not unequivocally increasing nor is MLD shoaling. We
      find that while SST increases at three study areas at midlatitudes,
      stratification both increases and decreases, and MLD deepens with enhanced
      deepening of winter MLDs at rates over 10 m  decade-1. These results rely on the
      estimation of several MLD and stratification indexes of different complexity on
      hydrographic profiles from long-term hydrographic time-series, ocean reanalysis,
      and Argo floats. Combining this information with estimated MLDs from buoyancy
      fluxes and the enhanced deepening/attenuation of the winter MLD trends due to
      changes in the Ekman pumping, MLD variability involves a subtle interplay between
      circulation and atmospheric forcing at midlatitudes. Besides, it is highlighted
      that the density difference between the surface and 200 m, the most widely used
      stratification index, should not be expected to reliably inform about changes in
      the vertical extent of mixing.

PMID- 29201585
TI  - Effects of iron nanoparticles on iron-corroding bacteria.
AB  - The toxicological effects of Fe3O4 nanoparticles were evaluated with an iron
      corroding bacterium (ICB) for preventing the biocorrosion of iron. Fe3O4
      nanoparticles of 18 nm were successfully prepared and characterized by
      transmission electron microscopy (TEM), X-ray diffraction (XRD) patterns and
      scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS). A
      halophilic ICB strain L4 was isolated from Ribandar saltpan Goa, India and
      identified biochemically and by 16S rRNA gene sequence analysis as Halanaerobium
      sp. The Fe3O4 nanoparticles in increasing doses (0.1-100 mg/L) caused
      transformation in growth and sulfide production of ICB strain L4. SEM-EDS
      analysis revealed a deformed cell structure with adsorption of nanoparticle on
      the cell surface and increased cell size. Comet assay revealed genotoxic effect
      of Fe3O4 nanoparticles on strain L4 which resulted in dose-dependent DNA damage
      by increasing percentage tail DNA from 5 to 88% with increasing Fe3O4
      nanoparticles concentration. Furthermore, sulfide production rate was reduced to
      11.8% in presence of 100 mg/L Fe3O4 nanoparticles which reduced the corroding
      property of ICB strain L4; thus, it was unable to corrode the iron nail in
      presence of Fe3O4 nanoparticle. This work suggests the possible application of
      Fe3O4 nanoparticle in addressing biocorrosion problems faced by different
      industries.

PMID- 29201586
TI  - Silicon bioavailability in exocarp of Cucumis sativus Linn.
AB  - Scanning electron microscopy (SEM) and electron probe micro-analyzer (EPMA)
      techniques have been used to detect the silicon bioavailability in the exocarp of
      warty cucumber surface. Warts appear at the time of anthesis and are remnant part
      of spines/trichomes which on further fruit maturation abscised from the exocarp.
      Results of EPMA and phytolith analysis clearly revealed that the surface of
      exocarp (fruit) of Cucumis sativus Linn. containing warts has greater quantity of
      silicon as compared to the other part of the fruit. Besides silicon, some other
      elements were also found, on the fruit exocarp and its surrounding area. The
      other elements are magnesium (Mg), aluminum (Al), phosphorus (P), sulfur (S),
      potassium (K), calcium (Ca), iron (Fe), nickel (Ni), copper (Cu), and sodium. The
      percentage of silica is highest followed by Ni, Ca, Al, P, Mg, Fe, S, Cu, K, and
      Cl. Thus, this study clearly demonstrates that Cucumis sativus Linn. fruits which
      are used as salads and appetizers on daily basis are loaded with silicon and
      other useful elements and possess numerous health benefits.

PMID- 29201587
TI  - Quinolone-resistant clinical strains of Pseudomonas aeruginosa isolated from
      University Hospital in Tunisia.
AB  - In this study, we examined mutations in the quinolone resistance-determining
      regions (QRDRs) of the gyrA and parC genes of Pseudomonas aeruginosa (P.
      aeruginosa) clinical isolates collected from patients hospitalized in University
      Hospital of Monastir, Tunisia. A total of 81 P. aeruginosa strains, obtained from
      clinical specimens, were included in the present study. Isolates were tested
      against 11 different antibiotics by a disk diffusion method. Minimum inhibitory
      concentrations (MICs) of ciprofloxacin were evaluated by E test method. The gyrA
      and parC sequences genes amplified by polymerase chain reaction (PCR) were
      sequenced. The highest resistance rates were found for ciprofloxacin (100%),
      gentamicin (96%) and ticarcillin (93%). The lower resistance rates were obtained
      for imipenem (74%) and ceftazidime (70%). Notably, 54% of isolates resistant to
      ciprofloxacin were determined to be multi-drug resistant. The investigation of
      mutations in the nucleotide sequences of the gyrA and parC genes showed that 77%
      of isolates have a single mutation in both gyrA (Thr-83 -> Ile) and parC (Ser-87 
      > Leu). The emergence of ciprofloxacin resistance in clinical P. aeruginosa
      requires the establishment of appropriate antibiotherapy strategies in order to
      prescribe the most effective antibiotic treatment for preventing the emergence of
      multi-drug-resistant (MDR) P. aeruginosa strains.

PMID- 29201588
TI  - Reminders make people adhere better to a self-help sleep intervention.
AB  - The experiment presented in this paper investigated the effects of different
      kinds of reminders on adherence to automated parts of a cognitive behavioural
      therapy for insomnia (CBT-I) delivered via a mobile device. Previous studies
      report that computerized health interventions can be effective. However,
      treatment adherence is still an issue. Reminders are a simple technique that
      could improve adherence. A minimal intervention prototype in the realm of sleep
      treatment was developed to test the effects of reminders on adherence. Two
      prominent ways to determine the reminder-time are: a) ask users when they want to
      be reminded, and b) let an algorithm decide when to remind users. The prototype
      consisted of a sleep diary, a relaxation exercise and reminders. A within subject
      design was used in which the effect of reminders and two underlying principles
      were tested by 45 participants that all received the following three different
      conditions (in random order): a) event-based reminders b) time-based reminders c)
      no reminders. Both types of reminders improved adherence compared to no
      reminders. No differences were found between the two types of reminders.
      Opportunity and self-empowerment could partly mediate adherence to filling out
      the sleep diary, but not to the number of relaxation exercises conducted.
      Although the study focussed on CBT-I, we expect that designers of other
      computerized health interventions benefit from the tested opportunity and self
      empowerment principles for reminders to improve adherence, as well.

PMID- 29201589
TI  - Designing an ICT self-management service: suggestions from persons with type 2
      diabetes.
AB  - This paper reports the wishes and needs of people with type 2 diabetes (T2DM) for
      a future information and communication technology (ICT) self-management service
      to help manage their condition and their everyday life. Diabetes is a chronic
      disease affecting more and more people and placing increasing demands on health
      care. The self-management of diabetes includes instrumental and, decision-making
      skills and skills in managing daily activities, which may be supported by an ICT
      service. In this study we used a participatory design including two sessions of
      Future Workshop (FW) as part of a larger research project on the self-management
      of diabetes. Adults with type 2 diabetes participated in two FW sessions in which
      their expressed wishes and needs for an ICT service all fell under the broad
      category of Acceptance of the diagnosis, with three other suggestions; Trust in
      partnerships, Communication, and Individualized information. The participants'
      experience of the FW as a democratic process and their appreciation of mutual
      learning contributed to these results, which are consistent with the aims of
      person-centred care.

PMID- 29201590
TI  - Investigating pH based evaluation of fetal heart rate (FHR) recordings.
AB  - Cardiotocography (CTG) is a standard tool for the assessment of fetal well-being
      during pregnancy and delivery. However, its interpretation is associated with
      high inter- and intra-observer variability. Since its introduction there have
      been numerous attempts to develop computerized systems assisting the evaluation
      of the CTG recording. Nevertheless these systems are still hardly used in a
      delivery ward. Two main approaches to computerized evaluation are encountered in
      the literature; the first one emulates existing guidelines, while the second one
      is more of a data-driven approach using signal processing and computational
      methods. The latter employs preprocessing, feature extraction/selection and a
      classifier that discriminates between two or more classes/conditions. These
      classes are often formed using the umbilical cord artery pH value measured after
      delivery. In this work an approach to Fetal Heart Rate (FHR) classification using
      pH is presented that could serve as a benchmark for reporting results on the
      unique open-access CTU-UHB CTG database, the largest and the only freely
      available database of this kind. The overall results using a very small number of
      features and a Least Squares Support Vector Machine (LS-SVM) classifier, are in
      accordance to the ones encountered in the literature and outperform the results
      of a baseline classification scheme proving the utility of using advanced data
      processing methods. Therefore the achieved results can be used as a benchmark for
      future research involving more informative features and/or better classification
      algorithms.

PMID- 29201592
TI  - Understanding Rates of Marijuana Use and Consequences Among Adolescents in a
      Changing Legal Landscape.
AB  - Purpose of Review: There is not one answer to address whether marijuana use has
      increased, decreased, or stayed the same given changes in state legalization of
      medical and non-medical marijuana in the USA. Recent Findings: Evidence suggests
      some health benefits for medical marijuana; however, initiation of marijuana use
      is a risk factor for developing problem cannabis use. Though use rates have
      remained stable over recent years, about one in three 10th graders report
      marijuana use, most adolescents do not view the drug as harmful, and over 650,000
      youth aged 12 to 17 struggle with cannabis use disorder. Summary: Although the
      health benefits of medical marijuana are becoming better understood, more
      research is needed. Intervention and prevention programs must better address
      effects of marijuana, acknowledging that while there may be some benefits
      medically, marijuana use can affect functioning during adolescence when the brain
      is still developing.

PMID- 29201591
TI  - Optofluidic bioanalysis: fundamentals and applications.
AB  - Over the past decade, optofluidics has established itself as a new and dynamic
      research field for exciting developments at the interface of photonics,
      microfluidics, and the life sciences. The strong desire for developing
      miniaturized bioanalytic devices and instruments, in particular, has led to novel
      and powerful approaches to integrating optical elements and biological fluids on
      the same chip-scale system. Here, we review the state-of-the-art in optofluidic
      research with emphasis on applications in bioanalysis and a focus on waveguide
      based approaches that represent the most advanced level of integration between
      optics and fluidics. We discuss recent work in photonically reconfigurable
      devices and various application areas. We show how optofluidic approaches have
      been pushing the performance limits in bioanalysis, e.g. in terms of sensitivity
      and portability, satisfying many of the key requirements for point-of-care
      devices. This illustrates how the requirements for bianalysis instruments are
      increasingly being met by the symbiotic integration of novel photonic
      capabilities in a miniaturized system.

PMID- 29201593
TI  - A Policy Perspective on the Global Use of Smokeless Tobacco.
AB  - Background: Globally, over 300 million people consume diverse smokeless tobacco
      (ST) products. They are addictive, cause cancer, increased cardiovascular
      mortality risks and poor pregnancy outcomes. Purpose of Review: To identify gaps
      in implementing key ST demand-reduction measures, focused literature reviews were
      conducted and findings synthesized according to relevant WHO Framework Convention
      on Tobacco Control (FCTC) Articles. Recent Findings: The literature supports
      implementation of ST demand-reduction measures. For taxation, labelling and
      packaging, most administrations have weaker policies for ST than cigarettes.
      Capacity to regulate ST contents and offer cessation support is lacking. There is
      poor compliance with bans on ST advertising, promotion and sponsorship. Summary:
      The literature on implementation of WHO FCTC for ST is limited. Although
      strengths of ST demand-control activities are currently identifiable from
      available literature, full implementation of FCTC is lacking. A wider evidence
      based response to WHO FCTC is proposed, particularly for countries facing the
      greatest disease burdens.

PMID- 29201594
TI  - Translational Genetic Modelling of 3D Craniofacial Dysmorphology: Elaborating the
      Facial Phenotype of Neurodevelopmental Disorders Through the "Prism" of
      Schizophrenia.
AB  - Purpose of Review: In the context of human developmental conditions, we review
      the conceptualisation of schizophrenia as a neurodevelopmental disorder, the
      status of craniofacial dysmorphology as a clinically accessible index of brain
      dysmorphogenesis, the ability of genetically modified mouse models of
      craniofacial dysmorphology to inform on the underlying dysmorphogenic process and
      how geometric morphometric techniques in mutant mice can extend quantitative
      analysis. Recent Findings: Mutant mice with disruption of neuregulin-1, a gene
      associated meta-analytically with risk for schizophrenia, constitute proof-of
      concept studies of murine facial dysmorphology in a manner analogous to clinical
      studies in schizophrenia. Geometric morphometric techniques informed on the
      topography of facial dysmorphology and identified asymmetry therein. Summary:
      Targeted disruption in mice of genes involved in individual components of
      developmental processes and analysis of resultant facial dysmorphology using
      geometric morphometrics can inform on mechanisms of dysmorphogenesis at levels of
      incisiveness not possible in human subjects.

PMID- 29201595
TI  - Microbes Tickling Your Tummy: the Importance of the Gut-Brain Axis in Parkinson's
      Disease.
AB  - Purpose of Review: Patients suffering from Parkinson's disease (PD) are known to
      experience gastrointestinal dysfunction that might precede the onset of motor
      symptoms by several years. Evidence suggests an important role of the gut-brain
      axis in PD pathogenesis. These interactions might be essentially influenced by
      the gut microbiota. Here, we review recent findings supporting that changes in
      the gut microbiota composition might be a trigger for inflammation contributing
      to neurodegeneration in PD. Recent Findings: Recent research revealed that PD
      patients exhibit a pro-inflammatory microbiota profile in their intestinal tract
      that might increase gut permeability, allowing leakage of bacterial products and
      inflammatory mediators from the intestines. Evidence in literature indicates that
      alpha-synuclein deposition might start in the enteric nervous system by pro
      inflammatory immune activity and then propagates to the CNS. Alternatively, the
      peripheral inflammatory response could impact the brain through systemic
      mechanisms. Summary: A better understanding of the gut-brain interactions and the
      role of the intestinal microbiota in the regulation of immune responses might
      bring new insights in PD pathological progression and might lead to novel
      diagnostics and therapeutic approaches.

PMID- 29201596
TI  - Definitions and Epidemiology of Endodontic Infections.
AB  - Purpose of Review: This review describes the recent findings from epidemiological
      studies on endodontic infections. The recent literature was screened for studies
      on the prevalence of primary apical periodontitis and posttreatment apical
      periodontitis in various populations. Recent Findings: Twenty-nine articles
      reporting data on the prevalence of primary or posttreatment apical periodontitis
      from all over the world were included. The prevalence of apical periodontitis
      varied between 7 and 86%, while that of posttreatment apical periodontitis varied
      between 10 and 62%. The quality of the coronal restoration and the root filling
      appears to be the major predictors of apical periodontitis. Summary: The recent
      findings from epidemiological studies on the prevalence of primary and
      posttreatment apical periodontitis in various populations are not substantially
      different from those from earlier years. It appears that the health of periapical
      tissues has not majorly improved in the general population.

PMID- 29201597
TI  - Current Concepts of Epigenetics and Its Role in Periodontitis.
AB  - Purpose: The focus of this review is to provide an overview of the recent
      findings on the role of epigenetic mechanisms in periodontal disease, including
      disease susceptibility, progression, and as potential treatment options. Recent
      Findings: The findings on the influence of oral pathogens on epigenetic
      regulation of pathogen recognition receptors, such as Toll-like receptors, as
      well as pro-inflammatory cytokines suggest an important role for epigenetics in
      the regulation of the host immune response. Recent studies also show that the
      epigenetic pattern in periodontitis lesions differ from that of healthy and
      gingivitis tissue. In addition, these patterns differ between tissues in the same
      individual. Research is also indicating a role for both DNA methylation and
      histone acetylation on cells osteogenic differentiation and bone regeneration.
      Summary: Knowledge of epigenetic pattern in periodontal diseases may add not only
      to the knowledge of susceptibility of the disease but may also be a diagnostic
      tool to identify patients at risk to develop the severe form of periodontitis. In
      addition, recent research within gene therapy and tissue engineering indicate a
      role for epigenetics also to improve regeneration of periodontal tissues.

PMID- 29201598
TI  - Use of Probiotics and Oral Health.
AB  - Purpose of Review: The purpose of this study is to critically assess recent
      studies concerning the use of probiotics to control periodontal diseases, dental
      caries and halitosis (oral malodour). Recent Findings: Clinical studies have
      shown that probiotics when allied to conventional periodontal treatment can
      ameliorate microbial dysbiosis and produce significant improvement in clinical
      indicators of disease. However, this effect is often not maintained by the host
      after the end of probiotic use. Current probiotics also show limited effects in
      treating caries and halitosis. Novel approaches based up on replacement therapy
      and using highly abundant health-associated oral species, including nitrate
      reducing bacteria, have been proposed to improve persistence of probiotic strains
      and maintain oral health benefits. Summary: Probiotics have potential in the
      management of multifactorial diseases such as the periodontal diseases and
      caries, by more effectively addressing the host-microbial interface to restore
      homeostasis that may not be achieved with conventional treatments.

PMID- 29201599
TI  - Combining Adoptive Treg Transfer with Bone Marrow Transplantation for
      Transplantation Tolerance.
AB  - Purpose of Review: The mixed chimerism approach is an exceptionally potent
      strategy for the induction of donor-specific tolerance in organ transplantation
      and so far the only one that was demonstrated to work in the clinical setting.
      Regulatory T cells (Tregs) have been shown to improve chimerism induction in
      experimental animal models. This review summarizes the development of innovative
      BMT protocols using therapeutic Treg transfer for tolerance induction. Recent
      Findings: Treg cell therapy promotes BM engraftment in reduced conditioning
      protocols in both, mice and non-human primates. In mice, transfer of polyclonal
      recipient Tregs was sufficient to substitute cytotoxic recipient conditioning.
      Treg therapy prevented chronic rejection of skin and heart allografts related to
      tissue-specific antigen disparities, in part by promoting intragraft Treg
      accumulation. Summary: Adoptive Treg transfer is remarkably effective in
      facilitating BM engraftment in reduced-intensity protocols in mice and non-human
      primates. Furthermore, it promotes regulatory mechanisms that prevent chronic
      rejection.

PMID- 29201600
TI  - Donation, Not Disease! A Multiple-Hit Hypothesis on Development of Post-Donation
      Kidney Disease.
AB  - Purpose of Review: The risks following living kidney donation has been the
      subject of rigorous investigation in the past several decades. How to utilize the
      burgeoning new knowledge base to better the risk assessment, education, and
      health maintenance of donors is unclear. We review the physiologic and
      epidemiologic evidences on the post-donation state and submit a multiple-hit
      hypothesis to reconcile the finite elevation in risk of kidney disease after
      donation with the benign course of most kidney donors. Recent Findings: The risk
      of end-stage kidney disease is higher in kidney donors compared to similarly
      healthy non-kidney donors. Nonetheless, post-donation kidney disease is uncommon
      and arises mostly in the setting of other "hits"-either a "first hit" present at
      birth or a "second hit" acquired later in life. Summary: The transplant
      community's focus should be directed toward (1) personalized risk assessment to
      inform consent before donation and (2) preventing and treating development of
      "second hits" following kidney donation.

PMID- 29201601
TI  - A tracked robot with novel bio-inspired passive "legs".
AB  - For track-based robots, an important aspect is the suppression design, which
      determines the trafficability and comfort of the whole system. The trafficability
      limits the robot's working capability, and the riding comfort limits the robot's
      working effectiveness, especially with some sensitive instruments mounted on or
      operated. To these aims, a track-based robot equipped with a novel passive bio
      inspired suspension is designed and studied systematically in this paper. Animal
      or insects have very special leg or limb structures which are good for motion
      control and adaptable to different environments. Inspired by this, a new track
      based robot is designed with novel "legs" for connecting the loading wheels to
      the robot body. Each leg is designed with passive structures and can achieve very
      high loading capacity but low dynamic stiffness such that the robot can move on
      rough ground similar to a multi-leg animal or insect. Therefore, the
      trafficability and riding comfort can be significantly improved without losing
      loading capacity. The new track-based robot can be well applied to various
      engineering tasks for providing a stable moving platform of high mobility, better
      trafficability and excellent loading capacity.

PMID- 29201602
TI  - Ethical framework of assistive devices: review and reflection.
AB  - The population of ageing is growing significantly over the world, and there is an
      emerging demand for better healthcare services and more care centres. Innovations
      of Information and Communication Technology has resulted in development of
      various types of assistive robots to fulfil elderly's needs and independency,
      whilst carrying out daily routine tasks. This makes it vital to have a clear
      understanding of elderly's needs and expectations from assistive robots. This
      paper addresses current ethical issues to understand elderly's prime needs. Also,
      we consider other general ethics with the purpose of applying these theories to
      form a proper ethics framework. In the ethics framework, the ethical concerns of
      senior citizens will be prioritized to satisfy elderly's needs and also to
      diminish related expenses to healthcare services.

PMID- 29201603
TI  - Characterizing dynamic behaviors of three-particle paramagnetic microswimmer near
      a solid surface.
AB  - Particle-based magnetically actuated microswimmers have the potential to act as
      microrobotic tools for biomedical applications. In this paper, we report the
      dynamic behaviors of a three-particle paramagnetic microswimmer. Actuated by a
      rotating magnetic field with different frequencies, the microswimmer exhibits
      simple rotation and propulsion. When the input frequency is below 8 Hz, it
      exhibits simple rotation on the substrate, whereas it shows propulsion with
      varied poses when subjected to a frequency between 8 and 15 Hz. Furthermore, a
      solid surface that enhances swimming velocity was observed as the microswimmer is
      actuated near a solid surface. Our simulation results testify that the surface
      enhanced swimming near a solid surface is because of the induced pressure
      difference in the surrounding fluid of the microagent.

PMID- 29201604
TI  - Improved 3D measurement with a novel preprocessing method in DFP.
AB  - Shadow and background are two common factors in digital fringe projection, which
      lead to ambiguity in three-dimensional measurement and thereby need to be
      seriously considered. Preprocessing is often needed to segment the object from
      invalid points. The existing segmentation approaches based on modulation normally
      perform well in pure dark background circumstances, which, however, lose accuracy
      in situations of white or complex background. In this paper, an accurate shadow
      and background removal technique is proposed, which segments the shadow by one
      threshold from modulation histogram and segments the background by the threshold
      in intensity histogram. Experiments are well designed and conducted to verify the
      effectiveness and reliability of the proposed method.

PMID- 29201605
TI  - Culture-Free Detection of Crop Pathogens at the Single-Cell Level by Micro-Raman
      Spectroscopy.
AB  - The rapid and sensitive identification of invasive plant pathogens has important
      applications in biotechnology, plant quarantine, and food security. Current
      methods are far too time-consuming and need a pre-enrichment period ranging from
      hours to days. Here, a micro-Raman spectroscopy-based bioassay for culture-free
      pathogen quarantine inspection at the single cell level within 40 min is
      presented. The application of this approach can readily and specifically detect
      plant pathogens Burkholderia gladioli pv. alliicola and Erwinia chrysanthemi that
      are closely related pathogenically. Furthermore, the single-bacterium detection
      was able to discriminate them from a reference Raman spectral library including
      multiple quarantine-relevant pathogens with broad host ranges and an array of
      pathogenic variants. To show the usefulness of this assay, Burkholderia gladioli
      pv. alliicola and Erwinia chrysanthemi are detected at single-bacterium level in
      plant tissue lesions without pre-enrichment. The results are confirmed by the
      plate-counting method and a genetic molecular approach, which display comparable
      recognition ratios to the Raman spectroscopy-based bioassay. The results
      represent a critical step toward the use of micro-Raman spectroscopy in rapid and
      culture-free discrimination of quarantine relevant plant pathogens.

PMID- 29201606
TI  - A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy
      (SMA) Actuators.
AB  - Underactive bladder or detrusor underactivity (DU) is defined as a reduction of
      contraction strength or duration of the bladder wall. Despite the serious
      healthcare implications of DU, there are limited solutions for affected
      individuals. A flexible 3D printed implantable device driven by shape memory
      alloys (SMA) actuators is presented here for the first time to physically
      contract the bladder to restore voluntary control of the bladder for individuals
      suffering from DU. This approach is used initially in benchtop experiments with a
      rubber balloon acting as a model for the rat bladder to verify its potential for
      voiding, and that the operating temperatures are safe for the eventual
      implantation of the device in a rat. The device is then implanted and tested on
      an anesthetized rat, and a voiding volume of more than 8% is successfully
      achieved for the SMA-based device without any surgical intervention or drug
      injection to relax the external sphincter.

PMID- 29201607
TI  - In Situ Ligation of High- and Low-Affinity Ligands to Cell Surface Receptors
      Enables Highly Selective Recognition.
AB  - This paper reports an entirely unexplored concept of simultaneously recognizing
      two receptors using high- and low-affinity ligands through ligating them in situ
      on the target cell surface. This de novo approach is inspired by the pretargeting
      strategy frequently applied in molecular imaging, and has now evolved as the
      basis of a new paradigm for visualizing target cells with a high imaging
      contrast. A distinct advantage of using a labeled low-affinity ligand such as
      glycan is that the excess labeled ligand can be washed away from the cells,
      whereas the ligand bound to the cell, even at the milli molar affinity level, can
      be anchored by a bioorthogonal reaction with a pretargeted high-affinity ligand
      on the surface. Consequently, nonspecific background is minimized, leading to
      improved imaging contrast. Importantly, despite previously unexplored for
      molecular imaging, a notoriously weak glycan/lectin interaction can now be
      utilized as a highly selective ligand to the targets.

PMID- 29201608
TI  - Toward Bioelectronic Medicine-Neuromodulation of Small Peripheral Nerves Using
      Flexible Neural Clip.
AB  - Neural modulation technology and the capability to affect organ function have
      spawned the new field of bioelectronic medicine. Therapeutic interventions depend
      on wireless bioelectronic neural interfaces that can conformally and easily
      attach to small (few hundred micrometers) nerves located deep in the body without
      neural damage. Besides size, factors like flexibility and compliance to attach
      and adapt to visceral nerves associated moving organs are of paramount importance
      and have not been previously addressed. This study proposes a novel flexible
      neural clip (FNC) that can be used to interface with a variety of different
      peripheral nerves. To illustrate the flexibility of the design, this study
      stimulates the pelvic nerve, the vagus nerve, and branches of the sciatic nerve
      and evaluates the feasibility of the design in modulating the function of each of
      these nerves. It is found that this FNC allows fine-tuning of physiological
      processes such as micturition, heart rate, and muscle contractions. Furthermore,
      this study also tests the ability of wirelessly powered FNC to enable remote
      modulation of visceral pelvic nerves located deep in the body. These results show
      that the FNC can be used with a range of different nerves, providing one of the
      critical pieces in the field of bioelectronics medicines.

PMID- 29201609
TI  - A New Electron Acceptor with meta-Alkoxyphenyl Side Chain for Fullerene-Free
      Polymer Solar Cells with 9.3% Efficiency.
AB  - A new small molecule acceptor, m-ITIC-OR, based on indacenodithieno[3,2
      b]thiophene core with meta-alkoxyphenyl side chains, is designed and synthesized.
      The m-ITIC-OR film shows broader and redshift absorption compared to its solution
      and matched energy levels with a hexafluoroquinoxaline-based polymer donor-HFQx
      T. Here, polymer solar cells (PSCs) by blending an HFQx-T donor and an m-ITIC-OR
      acceptor as an active layer deliver the power conversion efficiency (PCE) of
      6.36% without any posttreatment. The investigations demonstrate that the HFQx-T:m
      ITIC-OR blend films possess higher and more balanced charge mobility, negligible
      bimolecular recombination, and nanoscale interpenetrating morphology after
      thermal annealing (TA) treatment. Through a simple TA treatment at 150  degrees C
      for 5 min, an impressive PCE of 9.3% is obtained. This efficiency is among one of
      the highest PCEs for additive free PSCs. This is the first time alkoxyphenyl side
      chain is introduced into nonfullerene electron acceptor; more interestingly, the
      new electron acceptor (m-ITIC-OR) in this work shows a great potential for highly
      efficient photovoltaic properties.

PMID- 29201610
TI  - Single Nucleotide Polymorphism Genotyping in Single-Molecule Electronic Circuits.
AB  - Establishing low-cost, high-throughput, simple, and accurate single nucleotide
      polymorphism (SNP) genotyping techniques is beneficial for understanding the
      intrinsic relationship between individual genetic variations and their biological
      functions on a genomic scale. Here, a straightforward and reliable single
      molecule approach is demonstrated for precise SNP authentication by directly
      measuring the fluctuations in electrical signals in an electronic circuit, which
      is fabricated from a high-gain field-effect silicon nanowire decorated with a
      single hairpin DNA, in the presence of different target DNAs. By simply comparing
      the proportion difference of a probe-target duplex structure throughout the
      process, this study implements allele-specific and accurate SNP detection. These
      results are supported by the statistical analyses of different dynamic parameters
      such as the mean lifetime and the unwinding probability of the duplex
      conformation. In comparison with conventional polymerase chain reaction and
      optical methods, this convenient and label-free method is complementary to
      existing optical methods and also shows several advantages, such as simple
      operation and no requirement for fluorescent labeling, thus promising a
      futuristic route toward the next-generation genotyping technique.

PMID- 29201611
TI  - Realizing the Embedded Growth of Large Li2O2 Aggregations by Matching Different
      Metal Oxides for High-Capacity and High-Rate Lithium Oxygen Batteries.
AB  - Large Li2O2 aggregations can produce high-capacity of lithium oxygen (Li-O2)
      batteries, but the larger ones usually lead to less-efficient contact between
      Li2O2 and electrode materials. Herein, a hierarchical cathode architecture based
      on different discharge characteristics of alpha-MnO2 and Co3O4 is constructed,
      which can enable the embedded growth of large Li2O2 aggregations to solve this
      problem. Through experimental observations and first-principle calculations, it
      is found that alpha-MnO2 nanorod tends to form uniform Li2O2 particles due to its
      preferential Li+ adsorption and similar LiO2 adsorption energies of different
      crystal faces, whereas Co3O4 nanosheet tends to simultaneously generate Li2O2
      film and Li2O2 nanosheets due to its preferential O2 adsorption and different
      LiO2 adsorption energies of varied crystal faces. Thus, the composite cathode
      architecture in which Co3O4 nanosheets are grown on alpha-MnO2 nanorods can
      exhibit extraordinary synergetic effects, i.e., alpha-MnO2 nanorods provide the
      initial nucleation sites for Li2O2 deposition while Co3O4 nanosheets provide
      dissolved LiO2 to promote the subsequent growth of Li2O2. Consequently, the
      composite cathode achieves the embedded growth of large Li2O2 aggregations and
      thus exhibits significantly improved specific capacity, rate capability, and
      cyclic stability compared with the single metal oxide electrode.

PMID- 29201612
TI  - High Performance Solid Polymer Electrolytes for Rechargeable Batteries: A Self
      Catalyzed Strategy toward Facile Synthesis.
AB  - It is urgent to seek high performance solid polymer electrolytes (SPEs) via a
      facile chemistry and simple process. The lithium salts are composed of complex
      anions that are stabilized by a Lewis acid agent. This Lewis acid can initiate
      the ring opening polymerization. Herein, a self-catalyzed strategy toward facile
      synthesis of crosslinked poly(ethylene glycol) diglycidyl ether-based solid
      polymer electrolyte (C-PEGDE) is presented. It is manifested that the
      poly(ethylene glycol) diglycidyl ether-based solid polymer electrolyte possesses
      a superior electrochemical stability window up to 4.5 V versus Li/Li+ and
      considerable ionic conductivity of 8.9 * 10-5 S cm-1 at ambient temperature.
      Moreover, the LiFePO4/C-PEGDE/Li batteries deliver stable charge/discharge
      profiles and considerable rate capability. It is demonstrated that this self
      catalyzed strategy can be a very effective approach for high performance solid
      polymer electrolytes.

PMID- 29201613
TI  - Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a
      Gold Nanocluster/Lipid Core-Shell Nanocarrier.
AB  - The type II bacterial clustered, regularly interspaced, short palindromic repeats
      (CRISPR)-Cas9 (CRISPR-associated protein) system (CRISPR-Cas9) is a powerful
      toolbox for gene-editing, however, the nonviral delivery of CRISPR-Cas9 to cells
      or tissues remains a key challenge. This paper reports a strategy to deliver Cas9
      protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold
      nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV-1
      transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered
      into cell nuclei. This strategy is utilized to treat melanoma by designing sgRNA
      targeting Polo-like kinase-1 (Plk1) of the tumor. The nanoparticle (polyethylene
      glycol-lipid/GNs/Cas9 protein/sgPlk1 plasmid, LGCP) leads to >70% down-regulation
      of Plk1 protein expression of A375 cells in vitro. Moreover, the LGCP suppresses
      melanoma progress by 75% on mice. Thus, this strategy can deliver protein-nucleic
      acid hybrid agents for gene therapy.

PMID- 29201615
TI  - Nanoporous PbSe-SiO2 Thermoelectric Composites.
AB  - Nanoporous architecture has long been predicted theoretically for its proficiency
      in suppressing thermal conduction, but less concerned as a practical approach for
      better thermoelectric materials hitherto probably due to its technical
      challenges. This article demonstrates a study on nanoporous PbSe-SiO2 composites
      fabricated by a facile method of mechanical alloying assisted by subsequent wet
      milling and then spark plasma sintering. Owing to the formation of random
      nanopores and additional interface scattering, the lattice thermal conductivity
      is limited to a value as low as 0.56 W m-1 K-1 at above 600 K, almost the same
      low level achieved by introducing nanoscale precipitates. Besides, the room
      temperature electrical transport is found to be dominated by the grain-boundary
      potential barrier scattering, whose effect fades away with increasing
      temperatures. Consequently, a maximum ZT of 1.15 at 823 K is achieved in the PbSe
      + 0.7 vol% SiO2 composition with >20% increase in average ZT, indicating the
      great potential of nanoporous structuring toward high thermoelectric conversion
      efficiency.

PMID- 29201616
TI  - Realization of Quasi-Omnidirectional Solar Cells with Superior Electrical
      Performance by All-Solution-Processed Si Nanopyramids.
AB  - Large-scale (156 mm * 156 mm) quasi-omnidirectional solar cells are successfully
      realized and featured by keeping high cell performance over broad incident angles
      (theta), via employing Si nanopyramids (SiNPs) as surface texture. SiNPs are
      produced by the proposed metal-assisted alkaline etching method, which is an all
      solution-processed method and highly simple together with cost-effective.
      Interestingly, compared to the conventional Si micropyramids (SiMPs)-textured
      solar cells, the SiNPs-textured solar cells possess lower carrier recombination
      and thus superior electrical performances, showing notable distinctions from
      other Si nanostructures-textured solar cells. Furthermore, SiNPs-textured solar
      cells have very little drop of quantum efficiency with increasing theta,
      demonstrating the quasi-omnidirectional characteristic. As an overall result,
      both the SiNPs-textured homojunction and heterojunction solar cells possess
      higher daily electric energy production with a maximum relative enhancement
      approaching 2.5%, when compared to their SiMPs-textured counterparts. The quasi
      omnidirectional solar cell opens a new opportunity for photovoltaics to produce
      more electric energy with a low cost.

PMID- 29201614
TI  - CO2 Reduction: From the Electrochemical to Photochemical Approach.
AB  - Increasing CO2 concentration in the atmosphere is believed to have a profound
      impact on the global climate. To reverse the impact would necessitate not only
      curbing the reliance on fossil fuels but also developing effective strategies
      capture and utilize CO2 from the atmosphere. Among several available strategies,
      CO2 reduction via the electrochemical or photochemical approach is particularly
      attractive since the required energy input can be potentially supplied from
      renewable sources such as solar energy. In this Review, an overview on these two
      different but inherently connected approaches is provided and recent progress on
      the development, engineering, and understanding of CO2 reduction electrocatalysts
      and photocatalysts is summarized. First, the basic principles that govern
      electrocatalytic or photocatalytic CO2 reduction and their important performance
      metrics are discussed. Then, a detailed discussion on different CO2 reduction
      electrocatalysts and photocatalysts as well as their generally designing
      strategies is provided. At the end of this Review, perspectives on the
      opportunities and possible directions for future development of this field are
      presented.

PMID- 29201617
TI  - Mixed-Organic-Cation Tin Iodide for Lead-Free Perovskite Solar Cells with an
      Efficiency of 8.12.
AB  - In this work, a fully tin-based, mixed-organic-cation perovskite absorber (FA) x
      (MA)1-x SnI3 (FA = NH2CH = NH2+, MA = CH3NH3+) for lead-free perovskite solar
      cells (PSCs) with inverted structure is presented. By optimizing the ratio of FA
      and MA cations, a maximum power conversion efficiency of 8.12% is achieved for
      the (FA)0.75(MA)0.25SnI3-based device along with a high open-circuit voltage of
      0.61 V, which originates from improved perovskite film morphology and inhibits
      recombination process in the device. The cation-mixing approach proves to be a
      facile method for the efficiency enhancement of tin-based PSCs.

PMID- 29201618
TI  - A Facile Surface Reconstruction Mechanism toward Better Electrochemical
      Performance of Li4Ti5O12 in Lithium-Ion Battery.
AB  - Through a facile sodium sulfide (Na2S)-assisted hydrothermal treatment, clean and
      nondefective surfaces are constructed on micrometer-sized Li4Ti5O12 particles.
      The remarkable improvement of surface quality shows a higher first cycle
      Coulombic efficiency (~95%), a significantly enhanced cycling performance, and a
      better rate capability in electrochemical measurements. A combined study of Raman
      spectroscopy and inductive coupled plasma emission spectroscopy reveals that the
      evolution of Li4Ti5O12 surface in a water-based hydrothermal environment is a
      hydrolysis-recrystallization process, which can introduce a new phase of anatase
      TiO2. While, with a small amount of Na2S (0.004 mol L-1 at least), the spinel
      Li4Ti5O12 phase is maintained without a second phase. During this process, the
      alkaline environment created by Na2S and the surface adsorption of the sulfur
      containing group (HS- or S2-) can suppress the recrystallization of anatase-TiO2
      and renew the particle surfaces. This finding gives a better understanding of the
      surface-property relationship on Li4Ti5O12 and guidance on preparation and
      modification of electrode material other than coating or doping.

PMID- 29201619
TI  - Utilizing Co2+/Co3+ Redox Couple in P2-Layered Na0.66Co0.22Mn0.44Ti0.34O2 Cathode
      for Sodium-Ion Batteries.
AB  - Developing sodium-ion batteries for large-scale energy storage applications is
      facing big challenges of the lack of high-performance cathode materials. Here, a
      series of new cathode materials Na0.66Co x Mn0.66-x Ti0.34O2 for sodium-ion
      batteries are designed and synthesized aiming to reduce transition metal-ion
      ordering, charge ordering, as well as Na+ and vacancy ordering. An interesting
      structure change of Na0.66Co x Mn0.66-x Ti0.34O2 from orthorhombic to hexagonal
      is revealed when Co content increases from x = 0 to 0.33. In particular,
      Na0.66Co0.22Mn0.44Ti0.34O2 with a P2-type layered structure delivers a reversible
      capacity of 120 mAh g-1 at 0.1 C. When the current density increases to 10 C, a
      reversible capacity of 63.2 mAh g-1 can still be obtained, indicating a promising
      rate capability. The low valence Co2+ substitution results in the formation of
      average Mn3.7+ valence state in Na0.66Co0.22Mn0.44Ti0.34O2, effectively
      suppressing the Mn3+-induced Jahn-Teller distortion, and in turn stabilizing the
      layered structure. X-ray absorption spectroscopy results suggest that the charge
      compensation of Na0.66Co0.22Mn0.44Ti0.34O2 during charge/discharge is contributed
      by Co2.2+/Co3+ and Mn3.3+/Mn4+ redox couples. This is the first time that the
      highly reversible Co2+/Co3+ redox couple is observed in P2-layered cathodes for
      sodium-ion batteries. This finding may open new approaches to design advanced
      intercalation-type cathode materials.

PMID- 29201620
TI  - Anchoring CoFe2O4 Nanoparticles on N-Doped Carbon Nanofibers for High-Performance
      Oxygen Evolution Reaction.
AB  - The exploration of earth-abundant and high-efficiency electrocatalysts for the
      oxygen evolution reaction (OER) is of great significant for sustainable energy
      conversion and storage applications. Although spinel-type binary transition metal
      oxides (AB2O4, A, B = metal) represent a class of promising candidates for water
      oxidation catalysis, their intrinsically inferior electrical conductivity exert
      remarkably negative impacts on their electrochemical performances. Herein, we
      demonstrates a feasible electrospinning approach to concurrently synthesize
      CoFe2O4 nanoparticles homogeneously embedded in 1D N-doped carbon nanofibers
      (denoted as CoFe2O4@N-CNFs). By integrating the catalytically active CoFe2O4
      nanoparticles with the N-doped carbon nanofibers, the as-synthesized CoFe2O4@N
      CNF nanohybrid manifests superior OER performance with a low overpotential, a
      large current density, a small Tafel slope, and long-term durability in alkaline
      solution, outperforming the single component counterparts (pure CoFe2O4 and N
      doped carbon nanofibers) and the commercial RuO2 catalyst. Impressively, the
      overpotential of CoFe2O4@N-CNFs at the current density of 30.0 mA cm-2 negatively
      shifts 186 mV as compared with the commercial RuO2 catalyst and the current
      density of the CoFe2O4@N-CNFs at 1.8 V is almost 3.4 times of that on RuO2
      benchmark. The present work would open a new avenue for the exploration of cost
      effective and efficient OER electrocatalysts to substitute noble metals for
      various renewable energy conversion/storage applications.

PMID- 29201621
TI  - Thermal Release Transfer Printing for Stretchable Conformal Bioelectronics.
AB  - Soft neural electrode arrays that are mechanically matched between neural tissues
      and electrodes offer valuable opportunities for the development of disease
      diagnose and brain computer interface systems. Here, a thermal release transfer
      printing method for fabrication of stretchable bioelectronics, such as soft
      neural electrode arrays, is presented. Due to the large, switchable and
      irreversible change in adhesion strength of thermal release tape, a low-cost,
      easy-to-operate, and temperature-controlled transfer printing process can be
      achieved. The mechanism of this method is analyzed by experiments and fracture
      mechanics models. Using the thermal release transfer printing method, a
      stretchable neural electrode array is fabricated by a sacrificial-layer-free
      process. The ability of the as-fabricated electrode array to conform different
      curvilinear surfaces is confirmed by experimental and theoretical studies. High
      quality electrocorticography signals of anesthetized rat are collected with the
      as-fabricated electrode array, which proves good conformal interface between the
      electrodes and dura mater. The application of the as-fabricated electrode array
      on detecting the steady-state visual evoked potentials research is also
      demonstrated by in vivo experiments and the results are compared with those
      detected by stainless-steel screw electrodes.

PMID- 29201622
TI  - Self-Tuning n-Type Bi2(Te,Se)3/SiC Thermoelectric Nanocomposites to Realize High
      Performances up to 300  degrees C.
AB  - Bi2Te3 thermoelectric materials are utilized for refrigeration for decades, while
      their application of energy harvesting requires stable thermoelectric and
      mechanical performances at elevated temperatures. This work reveals that a steady
      zT of ~0.85 at 200 to 300  degrees C can be achieved by doping small amounts of
      copper iodide (CuI) in Bi2Te2.2Se0.8-silicon carbide (SiC) composites, where SiC
      nanodispersion enhances the flexural strength. It is found that CuI plays two
      important roles with atomic Cu/I dopants and CuI precipitates. The Cu/I dopants
      show a self-tuning behavior due to increasing solubility with increasing
      temperatures. The increased doping concentration increases electrical
      conductivity at high temperatures and effectively suppresses the intrinsic
      excitation. In addition, a large reduction of lattice thermal conductivity is
      achieved due to the "in situ" CuI nanoprecipitates acting as phonon-scattering
      centers. Over 60% reduction of bipolar thermal conductivity is achieved, raising
      the maximum useful temperature of Bi2Te3 for substantially higher efficiency. For
      module applications, the reported materials are suitable for segmentation with a
      conventional ingot. This leads to high device ZT values of ~0.9-1.0 and high
      efficiency up to 9.2% from 300 to 573 K, which can be of great significance for
      power generation from waste heat.

PMID- 29201623
TI  - Enhanced Charge Collection in MOF-525-PEDOT Nanotube Composites Enable Highly
      Sensitive Biosensing.
AB  - With the aim of a reliable biosensing exhibiting enhanced sensitivity and
      selectivity, this study demonstrates a dopamine (DA) sensor composed of
      conductive poly(3,4-ethylenedioxythiophene) nanotubes (PEDOT NTs) conformally
      coated with porphyrin-based metal-organic framework nanocrystals (MOF-525). The
      MOF-525 serves as an electrocatalytic surface, while the PEDOT NTs act as a
      charge collector to rapidly transport the electron from MOF nanocrystals. Bundles
      of these particles form a conductive interpenetrating network film that together:
      (i) improves charge transport pathways between the MOF-525 regions and (ii)
      increases the electrochemical active sites of the film. The electrocatalytic
      response is measured by cyclic voltammetry and differential pulse voltammetry
      techniques, where the linear concentration range of DA detection is estimated to
      be 2 * 10-6-270 * 10-6 m and the detection limit is estimated to be 0.04 * 10-6 m
      with high selectivity toward DA. Additionally, a real-time determination of DA
      released from living rat pheochromocytoma cells is realized. The combination of
      MOF5-25 and PEDOT NTs creates a new generation of porous electrodes for highly
      efficient electrochemical biosensing.

PMID- 29201624
TI  - Metallic Sn-Based Anode Materials: Application in High-Performance Lithium-Ion
      and Sodium-Ion Batteries.
AB  - With the fast-growing demand for green and safe energy sources, rechargeable ion
      batteries have gradually occupied the major current market of energy storage
      devices due to their advantages of high capacities, long cycling life, superior
      rate ability, and so on. Metallic Sn-based anodes are perceived as one of the
      most promising alternatives to the conventional graphite anode and have attracted
      great attention due to the high theoretical capacities of Sn in both lithium-ion
      batteries (LIBs) (994 mA h g-1) and sodium-ion batteries (847 mA h g-1). Though
      Sony has used Sn-Co-C nanocomposites as its commercial LIB anodes, to develop
      even better batteries using metallic Sn-based anodes there are still two main
      obstacles that must be overcome: poor cycling stability and low coulombic
      efficiency. In this review, the latest and most outstanding developments in
      metallic Sn-based anodes for LIBs and SIBs are summarized. And it covers the
      modification strategies including size control, alloying, and structure design to
      effectually improve the electrochemical properties. The superiorities and
      limitations are analyzed and discussed, aiming to provide an in-depth
      understanding of the theoretical works and practical developments of metallic Sn
      based anode materials.

PMID- 29201625
TI  - Sequentially Programmable and Cellularly Selective Assembly of Fluorescent
      Polymerized Vesicles for Monitoring Cell Apoptosis.
AB  - The introduction of controlled self-assembly into living organisms opens up
      desired biomedical applications in wide areas including bioimaging/assays, drug
      delivery, and tissue engineering. Besides the enzyme-activated examples reported
      before, controlled self-assembly under integrated stimuli, especially in the form
      of sequential input, is unprecedented and ultimately challenging. This study
      reports a programmable self-assembling strategy in living cells under
      sequentially integrated control of both endogenous and exogenous stimuli.
      Fluorescent polymerized vesicles are constructed by using cholinesterase
      conversion followed by photopolymerization and thermochromism. Furthermore, as a
      proof-of-principle application, the cell apoptosis involved in the overexpression
      of cholinesterase in virtue of the generated fluorescence is monitored, showing
      potential in screening apoptosis-inducing drugs. The approach exhibits multiple
      advantages for bioimaging in living cells, including specificity to
      cholinesterase, red emission, wash free, high signal-to-noise ratio.

PMID- 29201626
TI  - Rod-Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery.
AB  - Efficient microRNAs (miRNA) delivery into cells is a promising strategy for
      disease therapy, but is a major challenge because the available conventional
      nonviral vectors have significant drawbacks. In particular, after these vectors
      are entrapped in lysosomes, the escape efficiency of genes from lysosomes into
      the cytosol is less than 2%. Here, a novel approach for lethal-7a (let-7a)
      replacement therapy using rod-shaped active pure drug nanoparticles (~130 nm in
      length, PNPs) with a dramatically high drug-loading of ~300% as vectors is
      reported. Importantly, unlike other vectors, the developed PNPs/let-7a complexes
      (~178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the
      cytosol, achieving efficient intracellular delivery of let-7a and a 50% reduction
      in expression of the target protein (KRAS). Also, CNPs prolong the t1/2 of blood
      circulation by ~threefold and increase tumor accumulation by ~1.5-2-fold,
      resulting in significantly improved antitumor efficacies. Additionally, no damage
      to normal organs is observed following systemic injection of CNPs. In conclusion,
      rod-shaped active PNPs enable efficient and safe delivery of miRNA with
      synergistic treatment for disease. This nanoplatform would also offer a viable
      strategy for the potent delivery of proteins and peptides in vitro and in vivo.

PMID- 29201627
TI  - Dual-Color-Emitting Carbon Nanodots for Multicolor Bioimaging and Optogenetic
      Control of Ion Channels.
AB  - The development of intrinsically multicolor-emitting carbon nanodots (CNDs) has
      been one of the great challenges for their various fields of applications. Here,
      the controlled electronic structure engineering of CNDs is performed to emit two
      distinct colors via the facile surface modification with 4-octyloxyaniline. The
      so-called dual-color-emitting CNDs (DC-CNDs) can be stably encapsulated within
      poly(styrene-co-maleic anhydride) (PSMA). The prepared water-soluble DC-CNDs@PSMA
      can be successfully applied to in vitro and in vivo dual-color bioimaging and
      optogenetics. In vivo optical imaging can visualize the biodistribution of
      intravenously injected DC-CNDs@PSMA. In addition, the light-triggered activation
      of ion channel, channelrhodopsin-2, for optogenetic applications is demonstrated.
      As a new type of fluorophore, DC-CNDs offer a big insight into the design of
      charge-transfer complexes for various optical and biomedical applications.

PMID- 29201628
TI  - Aluminum-Doped Cesium Lead Bromide Perovskite Nanocrystals with Stable Blue
      Photoluminescence Used for Display Backlight.
AB  - Bright and stable blue emitters with narrow full-width at half-maxima are
      particularly desirable for applications in television displays and related
      technologies. Here, this study shows that doping aluminum (Al3+) ion into CsPbBr3
      nanocrystals (NCs) using AlBr3 can afford lead-halide perovskites NCs with stable
      blue photoluminescence. First, theoretical and experimental analyses reveal that
      the extended band gap and quantum confinement effect of elongated shape give rise
      to the desirable blueshifted emission. Second, the aluminum ion incorporation
      path is rationalized qualitatively by invoking fundamental considerations about
      binding relations in AlBr3 and its dimer. Finally, the absence of anion-exchange
      effect is corroborated when green CsPbBr3 and blue Al:CsPbBr3 NCs are mixed.
      Combinations of the above two NCs with red-emitting CdSe@ZnS NCs result in UV
      pumped white light-emitting diodes (LED) with an National Television System
      Committee (NTSC) value of 116% and ITU-R Recommendation B.T. 2020 (Rec. 2020) of
      87%. The color coordinates of the white LED are optimized at (0.32, 0.34) in CIE
      1931. The results suggest that low-cost, earth-abundant, solution-processable Al
      doped perovskite NCs can be promising candidate materials for blue down
      conversion layer in backlit displays.

PMID- 29201629
TI  - Rational Design of a Water-Storable Hierarchical Architecture Decorated with
      Amorphous Barium Oxide and Nickel Nanoparticles as a Solid Oxide Fuel Cell Anode
      with Excellent Sulfur Tolerance.
AB  - Solid oxide fuel cells (SOFCs), which can directly convert chemical energy stored
      in fuels into electric power, represent a useful technology for a more
      sustainable future. They are particularly attractive given that they can be
      easily integrated into the currently available fossil fuel infrastructure to
      realize an ideal clean energy system. However, the widespread use of the SOFC
      technology is hindered by sulfur poisoning at the anode caused by the sulfur
      impurities in fossil fuels. Therefore, improving the sulfur tolerance of the
      anode is critical for developing SOFCs for use with fossil fuels. Herein, a
      novel, highly active, sulfur-tolerant anode for intermediate-temperature SOFCs is
      prepared via a facile impregnation and limited reaction protocol. During
      synthesis, Ni nanoparticles, water-storable BaZr0.4Ce0.4Y0.2O3-delta (BZCY)
      perovskite, and amorphous BaO are formed in situ and deposited on the surface of
      a Sm0.2Ce0.8O1.9 (SDC) scaffold. More specifically, a porous SDC scaffold is
      impregnated with a well-designed proton-conducting perovskite oxide liquid
      precursor with the nominal composition of Ba(Zr0.4Ce0.4Y0.2)0.8Ni0.2O3-delta
      (BZCYN), calcined and reduced in hydrogen. The as-synthesized hierarchical
      architecture exhibits high H2 electro-oxidation activity, excellent operational
      stability, superior sulfur tolerance, and good thermal cyclability. This work
      demonstrates the potential of combining nanocatalysts and water-storable
      materials in advanced electrocatalysts for SOFCs.

PMID- 29201630
TI  - Avoidance of Harm From Treatment for ANCA-Associated Vasculitis.
AB  - Purpose of review With established immunosuppressant treatment regimens for anti
      neutrophil cytoplasm antibody-associated vasculitides (AAV), prognosis has
      significantly improved. The mainstay of treatment still comprises high-dose
      corticosteroids and cyclophosphamide for severe forms, although rituximab is
      being increasingly utilised instead of cyclophosphamide as induction therapy. AAV
      patients experience an excess of infections, malignancies and cardiovascular
      events as compared to the general population, which is a combination of the
      systemic inflammatory process associated with vasculitis and the adverse events
      from treatment. Recent findings Successful therapy should focus on suppressing
      disease activity and minimising treatment-related toxicity. Infection is the
      largest contributor to morbidity and mortality in the first year of treatment,
      and annual pneumococcal and influenza vaccinations, Pneumocystis jiroveci
      prophylaxis and tuberculosis (TB) and Hepatitis B virus screening are advised.
      Patients on high-dose corticosteroid treatment should have regular blood sugar
      monitoring, a FRAX assessment with vitamin D and calcium supplementation,
      consideration of prophylaxis for gastric ulcers and a cardiovascular risk
      assessment. Patients who are treated with cyclophosphamide could also receive
      MESNA to reduce the risk of chemical cystitis. Cyclophosphamide, methotrexate and
      azathioprine all require blood monitoring schedules due to the risk of bone
      marrow suppression, liver and renal toxicity. Hypogammaglobulinaemia is a
      recognised risk of rituximab treatment. Patients of reproductive age need to be
      counselled on the infertility risks with cyclophosphamide and the teratogenicity
      associated with it, methotrexate and mycophenolate mofetil. Summary A greater
      focus on identifying clinical and biological markers that will help identify
      those patients at greatest risk of relapse, e.g. GPA and PR3-ANCA specificity,
      from those patients at greatest risk of toxicity, e.g. increasing age and
      declining GFR, is required to allow treatment to be tailored accordingly.

PMID- 29201631
TI  - Infection: a Cause of and Cure for Cancer.
AB  - Purpose of Review: This article provides a brief overview of the role that
      infections play in cancer emergence and cancer treatment. Recent Findings: A
      select number of pathogens have been reported to increase the incidence of
      specific cancers (directly through altering gene expression or indirectly through
      inducing chronic inflammation). These have been referred to as oncogenic
      pathogens. Conversely, a subset of pathogens has been demonstrated to
      preferentially cause lysis of tumor cells, leading to tumor regression and
      improved anti-tumor immunity. These have been termed oncolytic pathogens.
      However, the contribution of non-oncogenic, non-oncolytic pathogens to both tumor
      growth and regression is likewise being increasingly recognized. Summary:
      Pathogens have both the ability to cause and cure cancer. However, the mechanisms
      underlying these pathogen-mediated outcomes are not fully understood. With the
      recent emergence of interest in the immunotherapy of cancer, it is important that
      future studies focus specifically on preventing the negative effects of oncogenic
      infections, deconstructing the positive role of oncolytic pathogens, and finally
      providing insight into the dual roles of non-oncolytic, non-oncogenic pathogens
      so that anti-pathogen immune responses can be harnessed as a transformative means
      to treat cancer.

PMID- 29201632
TI  - Active living in rural Appalachia: Using the rural active living assessment
      (RALA) tools to explore environmental barriers.
AB  - People residing in rural communities are more likely to be physically inactive
      and subsequently have elevated risks for chronic disease. Recent evidence has
      shown this could stem from environmental barriers, inadequate programming and
      policies directed at the promotion of physical activity (PA) in rural settings.
      The objective of this research was to assess active living features in rural
      towns and townships (n = 16) across seven counties in northwestern North Carolina
      (NC). The study utilized the Town-Wide and Street Segment components of the Rural
      Active Living Assessment (RALA) as well as the 2014 American Community Survey
      results. The assessments were conducted in the summer of 2016 in the rural
      Appalachia region of NC. Using the RALA town-wide assessment scoring system (0 -
      100), the range of scores was 18-84, with the mean being 50.06. Three towns had
      no sidewalks, nine towns had sidewalks on only one side of the main streets, and
      four had sidewalks on both sides of the main streets. One town was rated as
      highly walkable, seven towns as moderately walkable, five towns as moderately
      unwalkable, and three towns as highly unwalkable. The rural Appalachia region of
      NC offers unique topographic, geographic and environmental barriers to PA.
      However, our findings indicate many rural towns offer common PA amenities. Future
      research should utilize qualitative methods and a community-based participatory
      research approach to more fully understand the challenges with increasing PA in
      the rural and often isolated Appalachia communities.

PMID- 29201633
TI  - A peculiar case of asymptomatic spontaneous pneumomediastinum.
AB  - Objective: To present a case of asymptomatic spontaneous pneumomediastinum and
      review available evidence-based workup and management. Case presentation: A young
      Caucasian adult male with a history of inhalational drug use was admitted to the
      internal medicine service for evaluation of dehydration and mild rhabdomyolysis.
      Patient had been on the run from the police and had spent the last days prior to
      presentation without food, water, or shelter. On admission, patient had no
      complaints, except for thirst. It was detected on physical exam and chest x-ray
      that patient had subcutaneous emphysema and pneumomediastinum. The patient was
      treated conservatively and discharged after a period of observation. Conclusion:
      Spontaneous pneumomediastinum is benign and seen primarily in young adults. It is
      more commonly associated with symptoms like chest pain and/or dyspnea, making an
      asymptomatic case particularly distinctive. The etiologies and precipitating
      factors are varied and often an apparent cause isn't identified. The diagnostic
      approach involves chest x-ray and/or computed tomography (CT) chest with further
      workup being largely unnecessary. The tenants of management include bedrest,
      analgesics, and supplemental oxygen as needed.

PMID- 29201634
TI  - Innovative chest physiotherapy techniques (the MetaNeb(r) System) in the
      intubated child with extensive burns.
AB  - Introduction: The Metaneb(r) is a new generation Intrapulmonary Percussive
      Ventilation device utilised by the physiotherapist to assist airway clearance by
      providing calibrated oscillations during inspiration up to 3.8Hz. Predominantly
      used in the adult chronic respiratory patient, with anecdotal evidence in
      intubated patients, it was also proven to be safe in a paediatric lung model lab
      study. This case report outlines the first use of the Metaneb(r) with an
      intubated child in Australia. The 8 year old patient was retrieved to Lady
      Cilento Children's Hospital with 61% total body surface area flame burns. The
      child was difficult to ventilate, immobile, and had retained secretions. The
      chest x-ray (CXR) demonstrated multifocal regions of atelectasis. Study
      objectives: To report safe and effective use of the Metaneb(r) airway clearance
      in the paediatric intubated patient. Methods: The Metaneb(r) was applied using an
      open ended bagging circuit on Continuous High Frequency Oscillation mode for a
      period of 10 min per treatment. The circuit contained an inline nebuliser
      containing 5ml 0.9% normal saline. PEEP was maintained and variable volume
      breaths were delivered with suction performed as required. Outcome variables to
      be measured included sputum weight and quality, CXR, and Peak Inspiratory
      Pressure (PIP) values pre and post treatment. Vital signs were monitored
      throughout. Results: The patient's vital signs remained stable throughout
      intervention. After 4 days of treatment twice daily, there was resolution of
      focal changes on CXR, improvement in secretions, a reduction in PIP and the
      patient was extubated. Conclusion: The Metaneb(r) was used safely and effectively
      in this patient to assist in resolution of respiratory pathology. Metaneb(r)
      provided a new option for physiotherapy treatment when positioning and handling
      restrictions limited usual care. This ultimately optimised PICU Length of stay
      and patient morbidity and mortality. Metaneb(r) provided by Hill-Rom Australia.

PMID- 29201635
TI  - Successful use of guanfacine in a patient with chronic refractory cough: A case
      report.
AB  - Chronic idiopathic cough is a common and often frustrating complaint for patients
      as well as providers. When common etiologies of cough are ruled out and/or do not
      respond to usual treatments, neurogenic cough should be considered as a diagnosis
      of exclusion. Here, we report on a 58-year-old woman with an 8-year history of
      chronic, treatment-refractory cough of unknown etiology that we diagnosed as
      neurogenic cough and successfully treated with guanfacine monotherapy, with rapid
      and durable improvement in symptoms. This case was particularly challenging for a
      number of reasons, including a distant past smoking history and previous
      pneumonia, a significant psychiatric history, and a mildly deviated nasal septum
      and nasal osteophyte, all or some of which could have contributed to the etiology
      of the cough. This case illustrates that neurogenic cough should be a diagnostic
      consideration in patients presenting with chronic cough in whom other treatment
      modalities have failed, and also suggests that the therapeutic use of guanfacine
      in this clinical setting warrants future investigation.

PMID- 29201636
TI  - Laryngotracheoesophageal Cleft Type 3 and Severe Laryngotracheomalacia; Delayed
      Surgical Repair, a Treatment Challenge with an Excellent Outcome.
AB  - Laryngotracheoesophageal clefts (LTEC) are rare malformations which involve the
      upper respiratory and digestive tract. Surgical repair should be undertaken
      promptly to maintain a secure airway and prevent serious pulmonary aspiration.
      This paper reports the first case of LTEC type 3 with severe
      laryngotracheomalacia that was brought to Mofid children's hospital in late
      infancy with a poor health status. Delayed defect correction was our team
      strategy for the patient when she had achieved good weight gain. At the age of 22
      months in collaboration with the pediatric surgical and otolaryngologist team,
      the repair of the laryngeal cleft was done with lateral open approach method. She
      was discharged with tracheostomy and gastrostomy. In the next six months follow
      up after the surgery tracheostomy decannulation and gastrostomy tube removal were
      done and the infant is now in regular follow-up.

PMID- 29201637
TI  - Two patients with daptomycin induced eosinophilic pneumonia with different
      presentations and treatment.
AB  - We present two cases of daptomycin-induced eosinophilic pneumonia with
      characteristic chest x ray, CT scan and bronchoalveolar lavage (BAL) findings. It
      is not a commonly seen complication of Daptomycin but when it happens, it could
      cause a diagnostic and treatment dilemma. Patients could present acutely with
      hypoxic respiratory failure or a less dramatic chronic presentation is also
      possible. Our two patients presented with acute hypoxic respiratory failure and
      presentation resembles that of an infectious etiology. Diagnosis is confirmed by
      bronchoscopy with BAL in one of them and the other was treated empirically as the
      clinical and radiologic presentation was typical. Treatment includes removal of
      the offending agent, daptomycin. Corticosteroids are used if symptoms are severe
      and can result in rapid clinical improvement. There is no agreed upon dose and
      duration of steroids and we suggest a long taper of steroids for patients who
      present with severe symptoms and a short course steroid for patients with milder
      symptoms.

PMID- 29201638
TI  - Patterns of grey matter loss associated with motor subscores in early Parkinson's
      disease.
AB  - Classical motor symptoms of Parkinson's disease (PD) such as tremor, rigidity,
      bradykinesia, and axial symptoms are graded in the Movement Disorders Society
      Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. It is yet to be
      ascertained whether parkinsonian motor symptoms are associated with different
      anatomical patterns of neurodegeneration as reflected by brain grey matter (GM)
      alteration. This study aimed to investigate associations between motor subscores
      and brain GM at voxel level. High resolution structural MRI T1 scans from the
      Parkinson's Progression Markers Initiative (PPMI) repository were employed to
      estimate brain GM intensity of PD subjects. Correlations between GM intensity and
      total MDS-UPDRS III and its four subscores were computed. The total MDS-UPDRS III
      score was significantly negatively correlated bilaterally with putamen and
      caudate GM density. Lower anterior striatal GM intensity was significantly
      associated with higher rigidity subscores, whereas left-sided anterior striatal
      and precentral cortical GM reduction were correlated with severity of axial
      symptoms. No significant morphometric associations were demonstrated for tremor
      subscores. In conclusion, we provide evidence for neuroanatomical patterns
      underpinning motor symptoms in early PD.

PMID- 29201640
TI  - Connectome analysis with diffusion MRI in idiopathic Parkinson's disease:
      Evaluation using multi-shell, multi-tissue, constrained spherical deconvolution.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects
      extensive regions of the central nervous system. In this work, we evaluated the
      structural connectome of patients with PD, as mapped by diffusion-weighted MRI
      tractography and a multi-shell, multi-tissue (MSMT) constrained spherical
      deconvolution (CSD) method to increase the precision of tractography at tissue
      interfaces. The connectome was mapped with probabilistic MSMT-CSD in 21 patients
      with PD and in 21 age- and gender-matched controls. Mapping was also performed by
      deterministic single-shell, single tissue (SSST)-CSD tracking and probabilistic
      SSST-CSD tracking for comparison. A support vector machine was trained to predict
      diagnosis based on a linear combination of graph metrics. We showed that
      probabilistic MSMT-CSD could detect significantly reduced global strength,
      efficiency, clustering, and small-worldness, and increased global path length in
      patients with PD relative to healthy controls; by contrast, probabilistic SSST
      CSD only detected the difference in global strength and small-worldness. In
      patients with PD, probabilistic MSMT-CSD also detected a significant reduction in
      local efficiency and detected clustering in the motor, frontal temporoparietal
      associative, limbic, basal ganglia, and thalamic areas. The network-based
      statistic identified a subnetwork of reduced connectivity by MSMT-CSD and
      probabilistic SSST-CSD in patients with PD, involving key components of the
      cortico-basal ganglia-thalamocortical network. Finally, probabilistic MSMT-CSD
      had superior diagnostic accuracy compared with conventional probabilistic SSST
      CSD and deterministic SSST-CSD tracking. In conclusion, probabilistic MSMT-CSD
      detected a greater extent of connectome pathology in patients with PD, including
      those with cortico-basal ganglia-thalamocortical network disruptions. Connectome
      analysis based on probabilistic MSMT-CSD may be useful when evaluating the extent
      of white matter connectivity disruptions in PD.

PMID- 29201639
TI  - Visual feedback alters force control and functional activity in the visuomotor
      network after stroke.
AB  - Modulating visual feedback may be a viable option to improve motor function after
      stroke, but the neurophysiological basis for this improvement is not clear.
      Visual gain can be manipulated by increasing or decreasing the spatial amplitude
      of an error signal. Here, we combined a unilateral visually guided grip force
      task with functional MRI to understand how changes in the gain of visual feedback
      alter brain activity in the chronic phase after stroke. Analyses focused on brain
      activation when force was produced by the most impaired hand of the stroke group
      as compared to the non-dominant hand of the control group. Our experiment
      produced three novel results. First, gain-related improvements in force control
      were associated with an increase in activity in many regions within the
      visuomotor network in both the stroke and control groups. These regions include
      the extrastriate visual cortex, inferior parietal lobule, ventral premotor
      cortex, cerebellum, and supplementary motor area. Second, the stroke group showed
      gain-related increases in activity in additional regions of lobules VI and VIIb
      of the ipsilateral cerebellum. Third, relative to the control group, the stroke
      group showed increased activity in the ipsilateral primary motor cortex, and
      activity in this region did not vary as a function of visual feedback gain. The
      visuomotor network, cerebellum, and ipsilateral primary motor cortex have each
      been targeted in rehabilitation interventions after stroke. Our observations
      provide new insight into the role these regions play in processing visual gain
      during a precisely controlled visuomotor task in the chronic phase after stroke.

PMID- 29201641
TI  - Iron-related gene variants and brain iron in multiple sclerosis and healthy
      individuals.
AB  - Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet
      little is known about the association of common gene variants linked to iron
      regulation and pathological tissue changes in the brain. In this study, we
      investigated the association of genetic determinants linked to iron regulation
      with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC)
      and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched
      HCs were enrolled and obtained 3 T MRI examination. Three (3) single nucleotide
      polymorphisms (SNPs) associated with iron regulation were genotyped: two SNPs in
      the human hereditary hemochromatosis protein gene HFE: rs1800562 (C282Y mutation)
      and rs1799945 (H63D mutation), as well as the rs1049296 SNP in the transferrin
      gene (C2 mutation). The effects of disease and genetic status were studied using
      quantitative susceptibility mapping (QSM) voxel-based analysis (VBA) and region
      of-interest (ROI) analysis of the deep GM. The general linear model framework was
      used to compare groups. Analyses were corrected for age and sex, and adjusted for
      false discovery rate. We found moderate increases in susceptibility in the right
      putamen of participants with the C282Y (+ 6.1 ppb) and H63D (+ 6.9 ppb) gene
      variants vs. non-carriers, as well as a decrease in thalamic susceptibility of
      progressive MS patients with the C282Y mutation (left: - 5.3 ppb, right: - 6.7
      ppb, p < 0.05). Female MS patients had lower susceptibility in the caudate (- 6.0
      ppb) and putamen (left: - 3.9 ppb, right: - 4.6 ppb) than men, but only when they
      had a wild-type allele (p < 0.05). Iron-gene linked increases in putamen
      susceptibility (in HC and relapsing remitting MS) and decreases in thalamus
      susceptibility (in progressive MS), coupled with apparent sex interactions,
      indicate that brain iron in healthy and disease states may be influenced by
      genetic factors.

PMID- 29201642
TI  - The effect of duration of illness and antipsychotics on subcortical volumes in
      schizophrenia: Analysis of 778 subjects.
AB  - Background: The effect of duration of illness and antipsychotic medication on the
      volumes of subcortical structures in schizophrenia is inconsistent among previous
      reports. We implemented a large sample analysis utilizing clinical data from 11
      institutions in a previous meta-analysis. Methods: Imaging and clinical data of
      778 schizophrenia subjects were taken from a prospective meta-analysis conducted
      by the COCORO consortium in Japan. The effect of duration of illness and daily
      dose and type of antipsychotics were assessed using the linear mixed effect model
      where the volumes of subcortical structures computed by FreeSurfer were used as a
      dependent variable and age, sex, duration of illness, daily dose of
      antipsychotics and intracranial volume were used as independent variables, and
      the type of protocol was incorporated as a random effect for intercept. The
      statistical significance of fixed-effect of dependent variable was assessed.
      Results: Daily dose of antipsychotics was positively associated with left globus
      pallidus volume and negatively associated with right hippocampus. It was also
      positively associated with laterality index of globus pallidus. Duration of
      illness was positively associated with bilateral globus pallidus volumes. Type of
      antipsychotics did not have any effect on the subcortical volumes. Discussion: A
      large sample size, uniform data collection methodology and robust statistical
      analysis are strengths of the current study. This result suggests that we need
      special attention to discuss about relationship between subcortical regional
      brain volumes and pathophysiology of schizophrenia because regional brain volumes
      may be affected by antipsychotic medication.

PMID- 29201643
TI  - Relationships between brain metabolite levels, functional connectivity, and
      negative mood in urologic chronic pelvic pain syndrome patients compared to
      controls: A MAPP research network study.
AB  - Until recently, the predominant pathology of chronic pelvic pain conditions was
      thought to reside in the peripheral tissues. However, mounting evidence from
      neuroimaging studies suggests an important role of the central nervous system in
      the pathogenesis of these conditions. In the present cross-sectional study,
      proton magnetic resonance spectroscopy (1H-MRS) of the brain was conducted in
      female patients with urologic chronic pelvic pain syndrome (UCPPS) to determine
      if they exhibit abnormal concentrations of brain metabolites (e.g. those
      indicative of heightened excitatory tone) in regions involved in the processing
      and modulation of pain, including the anterior cingulate cortex (ACC) and the
      anterior and posterior insular cortices. Compared to a group of age-matched
      healthy subjects, there were significantly higher levels of choline (p = 0.006,
      uncorrected) in the ACC of UCPPS patients. ACC choline levels were therefore
      compared with the region's resting functional connectivity to the rest of the
      brain. Higher choline was associated with greater ACC-to-limbic system
      connectivity in UCPPS patients, contrasted with lower connectivity in controls
      (i.e. an interaction). In patients, ACC choline levels were also positively
      correlated with negative mood. ACC gamma-aminobutyric acid (GABA) levels were
      lower in UCPPS patients compared with controls (p = 0.02, uncorrected), but this
      did not meet statistical correction for the 4 separate regional comparisons of
      metabolites. These results are the first to uncover abnormal GABA and choline
      levels in the brain of UCPPS patients compared to controls. Low GABA levels have
      been identified in other pain syndromes and might contribute to CNS hyper
      excitability in these conditions. The relationships between increased ACC choline
      levels, ACC-to-limbic connectivity, and negative mood in UCPPS patients suggest
      that this metabolite could be related to the affective symptomatology of this
      syndrome.

PMID- 29201644
TI  - Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance
      of partial volume correction.
AB  - Mean diffusivity (MD) measured by diffusion tensor imaging can reflect
      microstructural alterations of the brain's gray matter (GM). Therefore, GM MD may
      be a sensitive marker of neurodegeneration related to Alzheimer's Disease (AD).
      However, due to partial volume effects (PVE), differences in MD may be
      overestimated because of a higher degree of brain atrophy in AD patients and in
      cases with mild cognitive impairment (MCI). Here, we evaluated GM MD changes in
      AD and MCI compared with healthy controls, and the effect of partial volume
      correction (PVC) on diagnostic utility of MD. We determined region of interest
      (ROI) and voxel-wise group differences and diagnostic accuracy of MD and volume
      measures between matched samples of 39 AD, 39 MCI and 39 healthy subjects before
      and after PVC. Additionally, we assessed whether effects of GM MD values on
      diagnosis were mediated by volume. ROI and voxel-wise group differences were
      reduced after PVC. When using these ROIs for predicting group separation in
      logistic models, both PVE corrected and uncorrected GM MD values yielded a poorer
      diagnostic accuracy in single predictor models than regional volume. For the
      discrimination of AD patients and healthy controls, the effect of GM MD on
      diagnosis was significantly mediated by volume of hippocampus and posterior
      cingulate ROIs. Our results suggest that GM MD measurements are strongly
      confounded by PVE in the presence of brain atrophy, underlining the necessity of
      PVC when using these measurements as specific metrics of microstructural tissue
      degeneration. Independently of PVC, regional MD was not superior to regional
      volume in separating prodromal and clinical stages of AD from healthy controls.

PMID- 29201645
TI  - Promoter haplotypes of interleukin-10 gene linked to cortex plasticity in
      subjects with risk of Alzheimer's disease.
AB  - The Alzheimer's disease (AD) aetiologic event is associated with brain
      inflammatory processes. In this study, we consider a haplotype of the IL-10 gene
      promoter region, - 1082A/- 819 T/- 592A (ATA haplotype), which is an additive and
      independent genetic risk factor for AD. Episodic memory change is the most
      striking cognitive alteration in AD. It remains unclear whether episodic memory
      networks can be affected by the ATA haplotype variant in amnestic mild cognitive
      impairment (aMCI), and if so, how this occurs. Thirty-nine aMCI patients and 30
      healthy controls underwent resting-state functional magnetic resonance imaging.
      An imaging genetics approach was then utilized to investigate disease-related
      differences in episodic memory networks between the groups based on ATA haplotype
      by-aMCI interactions. Gene-brain-behaviour relationships were then further
      examined. This study found that the ATA haplotype risk variant was associated
      with abnormal functional communications in the hippocampus-frontoparietal
      cortices, especially in the left hippocampal network. Moreover, these ATA
      haplotype carriers showed a distinct phase of hyperactivity in normal aging, with
      rapid declines of brain function in aMCI subjects when compared to non-ATA
      haplotype carriers. These findings added to the accumulating evidence that
      promoter haplotypes of IL-10 may be important modulators of the development of
      aMCI.

PMID- 29201646
TI  - Laser scanning laser diode photoacoustic microscopy system.
AB  - The development of low-cost and fast photoacoustic microscopy systems enhances
      the clinical applicability of photoacoustic imaging systems. To this end, we
      present a laser scanning laser diode-based photoacoustic microscopy system. In
      this system, a 905 nm, 325 W maximum output peak power pulsed laser diode with 50
      ns pulsewidth is utilized as the light source. A combination of aspheric and
      cylindrical lenses is used for collimation of the laser diode beam. Two
      galvanometer scanning mirrors steer the beam across a focusing aspheric lens. The
      lateral resolution of the system was measured to be ~21 MUm using edge spread
      function estimation. No averaging was performed during data acquisition. The
      imaging speed is ~370 A-lines per second. Photoacoustic microscopy images of
      human hairs, ex vivo mouse ear, and ex vivo porcine ovary are presented to
      demonstrate the feasibility and potentials of the proposed system.

PMID- 29201647
TI  - qPCR primer design revisited.
AB  - Primers are arguably the single most critical components of any PCR assay, as
      their properties control the exquisite specificity and sensitivity that make this
      method uniquely powerful. Consequently, poor design combined with failure to
      optimise reaction conditions is likely to result in reduced technical precision
      and false positive or negative detection of amplification targets. Despite the
      framework provided by the MIQE guidelines and the accessibility of wide-ranging
      support from peer-reviewed publications, books and online sources as well as
      commercial companies, the design of many published assays continues to be less
      than optimal: primers often lack intended specificity, can form dimers, compete
      with template secondary structures at the primer binding sites or hybridise only
      within a narrow temperature range. We present an overview of the main steps in
      the primer design workflow, with data that illustrate some of the unexpected
      variability that often occurs when theory is translated into practice. We also
      strongly urge researchers to report as much information about their assays as
      possible in their publications.

PMID- 29201648
TI  - Cultured fish epithelial cells are a source of alarm substance.
AB  - In various species of fishes, the importance of visual cues in the determination
      of environmental threat and subsequent predator avoidance is clear. Chemical cues
      also play an essential role facilitating predator avoidance. Among fish in the
      superorder Ostariophysi, club cells in the epidermis produce an alarm substance.
      Damage to the skin during a predation event releases an alarm substance (AS),
      which diffuses through the water column and binds to olfactory receptors of
      conspecifics. Fish then engage in a number of anti-predator behaviors that may
      include darting, schooling, or hiding. Behavioral responses to AS and
      physiological mechanisms that underlie those responses is an active area of
      study. However, because the precise chemical composition of the alarm substance
      is unknown, AS is not commercially available. Thus, when fish are challenged
      alarm substance in various experiments and assays it is obtained from skin
      extracts or via perfusion of shallow cuts in the epidermis. Both procedures are
      effective but require the animal to be sacrificed. In this manuscript, we report:
      *A non-invasive primary cell culture protocol to obtain alarm substance and does
      not require the model organism to be killed.*The demonstration of anti-predatory
      behaviors in fish exposed to alarm substance collected by this method.

PMID- 29201649
TI  - Direct deposition of silver nanoplates on quartz surface by sequence pre
      treatment hydroxylation and silanisation.
AB  - Silver nanoparticles deposited on quartz substrates are widely used as SERS
      substrates. The nanoparticles can be deposited directly from colloidal solution
      by dipping technique. However, the adhesion of the particles on the quartz
      surface is very poor. Normally the substrate is pre-treated with hydroxylation or
      silanisation process. In this paper, we have demonstrated that the application of
      the sequence pre-treatment hydroxylation and silanisation have improved the
      density of silver nanoplates desposited on the quartz surface. *Sequence
      hydroxylation and silanisation pre-treatment assists the deposition of the
      nanoplate on the surface.*Various immersion times of the quartz surface into the
      colloidal nanoplates determined size distributions and density surface of the
      nanoplates on the surface.

PMID- 29201650
TI  - Neutron microtomography of voids in gold.
AB  - Pilot attempt of the neutron microtomography of voids in gold carried out using
      the Neutron Microscope instrument is presented in the paper. The paper
      demonstrates that neutron microtomography provides viable alternative to X-ray
      imaging for the assessment of porosity in high atomic number materials. The model
      sample based on gold with artificially induced void system reveals segmented
      porosity with 5.4 micrometres voxel size and the spatial resolution close to 10
      micrometres.

PMID- 29201651
TI  - Mental disease, alcoholism and XDR-TB: loss to follow-up and resistance, the cost
      of an inadequate approach.

PMID- 29201652
TI  - Tackling latent tuberculous infection as part of a strategy for achieving
      tuberculosis elimination targets in China.

PMID- 29201653
TI  - Why are HIV-infected people not started on antiretroviral therapy? A mixed
      methods study from Gujarat, India.
AB  - Setting: Five purposively selected antiretroviral therapy (ART) centres in
      Gujarat, India. Objectives: To assess the proportion of ART-eligible people
      living with the human immunodeficiency virus (PLHIV) who were not initiated on
      ART within 2 months of being recorded as eligible, to identify factors associated
      with non-initiation and to explore reasons from the provider's perspective.
      Design: We used a mixed-methods design (triangulation) of 1) a quantitative phase
      involving record reviews and cohort analysis (Poisson regression) of PLHIV
      registered during April 2014-March 2015, and 2) a qualitative phase involving one
      to-one interviews with 25 providers. Results: Of 2079 ART-eligible PLHIV, 339
      (16%) were not started on ART within 2 months. PLHIV with CD4 counts of <350
      cells/MUl and patients who were labourers, hospitalised, bedridden or registered
      with certain ART centres were more likely not to be initiated on ART. Qualitative
      results were categorised into two broad themes: government health system- and
      patient-related challenges, which validated and complemented the quantitative
      findings. Conclusion: Several patient subgroups at greater risk of ART non
      initiation were identified, along with reasons for risk; this has important
      programme implications for achieving the UNAIDS 90-90-90 goal, and particularly
      the second 90 component of having 90% of diagnosed PLHIV start ART.

PMID- 29201654
TI  - Increasing isoniazid preventive therapy uptake in an HIV program in rural Papua
      New Guinea.
AB  - Setting: Tuberculosis (TB) is the leading cause of death among people living with
      the human immunodeficiency virus (PLHIV) in Papua New Guinea. Despite a policy
      for isoniazid preventive therapy (IPT) among PLHIV, implementation has been slow.
      Objective: We prospectively evaluated a standardized guided screening process,
      including TB diagnostic support, to increase IPT initiation in adult PLHIV on
      antiretro-viral treatment. Design: The guided process included a paper-based IPT
      screening tool that prompted review of patient history and TB symptoms and sputum
      analysis by smear microscopy and Xpert(r) MTB/RIF. Chest X-ray was performed at
      the provider's discretion. We quantified the yield of this guided process on IPT
      initiation and detection of TB and rifampicin resistance, and examined the
      contributions of each diagnostic modality. Results: Among 532 patients, TB was
      ruled out and IPT initiated in 450 (84%). TB was diagnosed and treatment was
      started in 82 (15%) patients. Xpert detected rifampicin resistance in one of 21
      patients (5%, 95%CI 0.24-21.3) with a positive Xpert result. All TB cases were
      diagnosed by chest X-ray and/or Xpert. No cases were diagnosed by sputum smear
      alone. Conclusion: A standardized guided process, including TB diagnostic
      support, successfully enabled IPT initiation and identified a large burden of
      undetected TB.

PMID- 29201655
TI  - Childhood tuberculosis in Mauritania, 2010-2015: diagnosis and outcomes in
      Nouakchott and the rest of the country.
AB  - Setting: The National Tuberculosis Programme, Mauritania. Objective: To compare
      the diagnosis and treatment outcomes of childhood tuberculosis (TB) cases (aged
      <15 years) registered between 2010 and 2015 inside and outside Nouakchott, the
      capital city. Design: This was a retrospective comparative cohort study. Results:
      A total of 948 children with TB were registered. The registration rate was 10
      times higher in Nouakchott. The proportion of children among all TB cases was
      higher inside than outside Nouakchott (7.5% vs. 4.6%, P < 0.01). Under-fives
      represented 225 (24%) of all childhood TB cases, of whom 204 (91%) were
      registered in Nouakchott. Extra-pulmonary TB was more common in Nouakchott, while
      smear-negative TB was less common. Treatment success was similar inside and
      outside Nouakchott (national rate 61%). The principal unsuccessful outcomes were
      loss to follow-up outside Nouakchott (21% vs. 11%, P < 0.01) while transfers out
      were more common in the city (25% vs. 14%, P = 0.01). Being aged <5 years (OR
      1.2, 95%CI 1.1-1.5) was associated with an unsuccessful outcome. Conclusion: This
      study indicates problems in the diagnosis and treatment of childhood TB in
      Mauritania, especially outside the city of Nouakchott. We suggest strengthening
      clinical diagnosis and management, improving communications between TB treatment
      centres and health services and pressing the TB world to develop more accurate
      and easy-to-use diagnostic tools for children.

PMID- 29201656
TI  - Age-stratified tuberculosis treatment outcomes in Zimbabwe: are we paying
      attention to the most vulnerable?
AB  - Setting: A high tuberculosis (TB) incidence, resource-limited urban setting in
      Zimbabwe. Objectives: To compare treatment outcomes among people initiated on
      first-line anti-tuberculosis treatment in relation to age and other explanatory
      factors. Design: This was a retrospective record review of routine programme
      data. Results: Of 2209 patients included in the study, 133 (6%) were children
      (aged <10 years), 132 (6%) adolescents (10-19 years), 1782 (81%) adults (20-59
      years) and 162 (7%) were aged ?60 years, defined as elderly. The highest
      proportion of smear-negative pulmonary TB cases was among the elderly (40%).
      Unfavourable outcomes, mainly deaths, increased proportionately with age, and
      were highest among the elderly (adjusted relative risk 3.8, 95%CI 1.3-10.7).
      Having previous TB, being human immunodeficiency virus positive and not on
      antiretroviral treatment or cotrimoxazole preventive therapy were associated with
      an increased risk of unfavourable outcomes. Conclusion: The elderly had the worst
      outcomes among all the age groups. This may be related to immunosuppressant
      comorbidities or other age-related diseases mis-classified as TB, as a
      significant proportion were smear-negative. Older persons need better adapted TB
      management and more sensitive diagnostic tools, such as Xpert(r) MTB/RIF.

PMID- 29201657
TI  - Tuberculosis among migrants in Bishkek, the capital of the Kyrgyz Republic.
AB  - Setting: Twenty-two first-line, two second-line and one tertiary health facility
      in Bishkek, the capital of Kyrgyzstan. Objectives: Among migrants, a marginalised
      population at risk for acquiring and transmitting tuberculosis (TB), we
      determined the proportion with TB among all registered TB cases. For those
      registered at primary-level facilities, we then reported on their demographic and
      clinical profiles and TB treatment outcomes. Design: This was a retrospective
      cohort analysis of 2012-2013 programme data. Results: Of 2153 TB patients
      registered in all health facilities, 969 (45%) were migrants, of whom 454 were
      registered in first-line facilities. Of these, 27% were cross-border migrants,
      50% had infectious TB and 12% had drug-resistant TB. Treatment success was 74%
      for new cases and 44% for retreatment TB (the World Health Organization target is
      ?85%). Failure in new and retreatment TB patients was respectively 8% and 25%.
      Twenty-six individuals started on a first-line anti-tuberculosis regimen failed
      due to multidrug-resistant TB. Eight (25%) of 32 individuals on a retreatment TB
      regimen also failed. Loss to follow-up was 10% for new and 19% for retreatment
      TB. Conclusion: Migrants constituted almost half of all TB patients, drug
      resistance is prevalent and treatment outcomes unsatisfactory. Fostering inter
      country collaboration and prioritising rapid TB diagnostics (Xpert(r) MTB/RIF)
      and innovative ways forward for improving treatment outcomes is urgent.

PMID- 29201658
TI  - Closing the gap: decentralising mental health care to primary care centres in one
      rural district of Rwanda.
AB  - Setting: Programmes that integrate mental health care into primary care settings
      could reduce the global burden of mental disorders by increasing treatment
      availability in resource-limited settings, including Rwanda. Objective: We
      describe patient demographics, service use and retention of patients in care at
      health centres (HC) participating in an innovative primary care integration
      programme, compared to patients using existing district hospital-based
      specialised out-patient care. Design: This was a retrospective cohort study using
      routinely collected data from six health centres and one district hospital from
      October 2014 to March 2015. Results: Of 709 patients, 607 were cared for at HCs;
      HCs accounted for 88% of the total visits for mental disorders. Patients with
      psychosis used HC services more frequently, while patients with affective
      disorders were seen more frequently at the district hospital. Of the 68% of
      patients who returned to care within 90 days of their first visit, 76% had a
      third visit within a further 90 days. There were no significant differences in
      follow-up rates between clinical settings. Conclusion: This study suggests that a
      programme of mentorship for primary care nurses can facilitate the
      decentralisation of out-patient mental health care from specialised district
      hospital mental health services to HCs in rural Rwanda.

PMID- 29201659
TI  - Mental disorders and drug/alcohol use in patients commencing extensively drug
      resistant tuberculosis treatment.
AB  - Mental disorders and alcohol/drug use worsen treatment outcomes for multidrug
      resistant tuberculosis (TB), but data are lacking for extensively drug-resistant
      (XDR) TB. We investigated the association of baseline mental disorders and
      alcohol/drug use on XDR-TB treatment outcomes in a retrospective study of 53 XDR
      TB Peruvian patients during 2010-2012. Logistic regression estimated the odds
      ratios for unfavourable XDR-TB treatment outcomes. Overall treatment success was
      25%. Mental disorders and drug/alcohol use were found in respectively 22.4% and
      20.4% of patients; neither were associated with unfavourable treatment outcomes.
      Future research should explore the relationship between mental health and
      drug/alcohol use in XDR-TB treatment outcomes.

PMID- 29201660
TI  - Operational aspects of bedaquiline implementation in Swaziland: report from the
      field.
AB  - Bedaquiline (BDQ) has been recommended by the World Health Organization for the
      treatment of multi-drug-resistant tuberculosis (MDR-TB) since 2013, but
      experience using the drug in high-burden, lower-income countries is limited and
      case studies are needed. Swaziland started using BDQ under national TB programme
      conditions in 2015 in four pilot sites. As of 1 December 2016, 93 patients had
      been initiated on BDQ, i.e., 19% of MDR-TB patients treated in the country.
      Swaziland has developed a systematic and efficient model for BDQ introduction in
      collaboration with several partners. This model is also being used to introduce
      other innovations and can serve as an example for other countries facing similar
      challenges.

PMID- 29201661
TI  - Occurrence of Clostridium perfringens in sausages sold in Meknes city, Morocco.
AB  - In Morocco, the consumption of meat products has experienced a sharp increase in
      recent years despite the presence of pathogenic bacteria due to hygiene failure.
      The present study was designed to determine the prevalence of Clostridium
      perfringens in sausages sold in Meknes city (Morocco) and to study the different
      factors affecting it contamination with this bacterium. To this end, 156 samples
      of sausages were taken in various shopping sites during one year from March 2014
      to February 2015. The microbiological analysis was carried out using the specific
      medium for isolation and identification of C. perfringens. ANOVA test was used
      for Statistical analysis (p< 0.05). The results of this study showed the presence
      of C. perfringens in 77.56% (121 of 156) samples, with 88.88% (32 of 36) in
      street vendors, 79.16% (19 of 24) in a weekly market, 70.83% (51 of 72) in
      butchery and 62.5% (15 of 24) in a supermarket. The average rate was 2.42 Log
      CFU/g, with a minimum value of 0 CFU/g recorded in several outlets and a maximum
      value of 6.05 Log CFU/g recorded in butchery. This study reveals that the
      contamination rate of sausages with C. perfringens is related to the sausages
      origin, retail sites and seasonal variations related to temperature increase.

PMID- 29201662
TI  - Treatment of severe mitral regurgitation caused by lesions in both leaflets using
      multiple mitral valve plasty techniques in a small dog.
AB  - Mitral valve plasty (MVP) is preferred over mitral valve replacement (MVR) for
      mitral regurgitation in humans because of its favorable effect on quality of
      life. In small dogs, it is difficult to repair multiple lesions in both leaflets
      using MVP. Herein, we report a case of severe mitral regurgitation caused by
      multiple severe lesions in the posterior leaflet (PL) in a mixed Chihuahua.
      Initially, we had planned MVR with an artificial valve. However, MVP combined
      with artificial chordal reconstruction of both leaflets, semicircular suture
      annuloplasty, and valvuloplasty using a newly devised direct scallop suture for
      the PL was attempted in this dog. The dog recovered well and showed no adverse
      cardiac signs, surviving two major operations. The dog died 4 years and 10 months
      after the MVP due to non-cardiovascular disease. Our additional technique of
      using a direct scallop suture seemed useful for PL repair involving multiple
      scallops in a small dog.

PMID- 29201663
TI  - Freeze all Policy: An Expanded Strategy Before Its Clinical Approval.

PMID- 29201664
TI  - Vitrification of Mouse MII Oocyte Decreases the Mitochondrial DNA Copy Number,
      TFAM Gene Expression and Mitochondrial Enzyme Activity.
AB  - Background: The objective of this study was determination of the changes in the
      reactive oxygen species (ROS) level, mitochondrial DNA (mtDNA) copy number and
      enzyme activity and transcription factor A (TFAM) gene expression in oocytes
      after vitrification. Methods: The oocytes at metaphase II (MII) stage (n=320)
      were collected from super-ovulated adult female mice (n=40). These oocytes were
      divided into vitrified and non-vitrified groups (n=160 in each group). After
      vitrification of oocytes, ROS level, mtDNA copy number; TFAM gene expression and
      mitochondrial enzymes activity (cytochrome C oxidase and succinate dehydrogenase)
      were assessed and compared with non-vitrified group. Visualization of the
      mitochondria was done using Mitotracker green staining under confocal microscope.
      Data were compared by independent T-test. Values of p<0.05 were considered as
      statistically significant. Results: The survival rate of oocytes after
      vitrification and warming was 96.05%. The intensity of cytochrome C oxidase
      activity, mtDNA copy number and TFAM gene expression in non-vitrified oocytes
      were significantly lower and the level of ROS was higher in vitrified oocytes in
      comparison with non-vitrified group (p<0.05). But the intensity of succinate
      dehydrogenase activity was not significantly different between the two groups.
      The pattern of mitochondrial distribution in two groups of study was similar but
      the intensity of Mitotracker green in non-vitrified oocytes was significantly
      higher than vitrified oocytes (p<0.05). Conclusion: This study showed that
      vitrification of mouse MII oocytes reduced the mtDNA copy number and
      mitochondrial cytochrome C oxidase activity by increasing ROS level, thus the
      subsequent embryo development may be affected.

PMID- 29201665
TI  - The Effect of Curcumin on TNF-alpha, IL-6 and CRP Expression in a Model of
      Polycystic Ovary Syndrome as an Inflammation State.
AB  - Background: Having low-grade chronic inflammation such as elevated C-reactive
      protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
      plays a crucial role in polycystic ovary syndrome (PCOS). This study aimed at
      investigating the therapeutic effects of curcumin on IL-6, CRP and TNF-alpha and
      symptoms of polycystic ovary syndrome. Methods: In this research, 72 female adult
      Wistar rats were divided into control (n=12), PCOS (n=12) and curcumin-treated
      PCOS groups (n=48). PCOS was induced by injection of estradiol valerate (2 mg/kg
      one-step). PCOS rats were divided into control and experimental groups which
      received daily intraperitoneal injection of curcumin. After 60 days of syndrome
      induction, ovaries were collected for histological and immunohistochemical
      evaluations. Serum IL-6 and CRP was detected by the ELISA kit. Data were analyzed
      using In-Stat 3 via one-way analysis of variance (ANOVA) and p<0.05 was
      considered statistically significant. Results: Histological studies showed a
      significant reduction in thickness of theca layer and increase in the number of
      corpus luteum (CL) diameter in the curcumin-treated group compared with the PCOS
      group; also inflammatory markers such as IL-6 and CRP significantly decreased in
      groups treated with curcumin compared with PCOS groups. Regarding
      immunohistochemical analysis, the expression of TNF-alpha in granulosa layer and
      follicular fluid of follicles and ovarian cysts in PCOS group was more than the
      control group's expression. However, expression of this factor in the ovaries
      treated with curcumin was decreased. Conclusion: This study showed that the anti
      inflammatory and antioxidant effects of curcumin on PCOS may be due to its
      inhibitory effect on expression and levels of TNF-alpha, serum IL-6 and CRP.

PMID- 29201666
TI  - Occult Form of Premature Ovarian Insufficiency in Women with Infertility and
      Oligomenorrhea as Assessed by Poor Ovarian Response Criteria.
AB  - Background: The purpose of this study was to evaluate the ability of poor ovarian
      response criteria to classify women presenting with infertility and
      oligomenorrhea as having "occult" premature ovarian insufficiency. Methods: This
      was a cross sectional study conducted at Aziz Medical Center, Karachi, Pakistan
      from 1st August 2015 to 31st July 2016. Women with infertility and oligomenorrhea
      were included. All eligible women underwent day 2 FSH level and an early
      follicular phase transvaginal ultrasound to assess the antral follicular count
      (AFC). All women then underwent the confirmatory test, of Anti-Mullerian Hormone
      (AMH) level. The main outcome measure was assignment to occult premature ovarian
      insufficiency (POI) after screening that used the criteria set out in fertility
      guideline for predicting the likely ovarian response to gonadotrophin
      stimulation. Another measure was to compare the sensitivity and specificity of
      the two index criteria, of FSH and AFC, relative to the emerging reference
      standard, of the AMH criterion. Results: The three criteria together classified
      59 (34.91%) women as occult POI in those with oligomenorrhea. The sensitivity,
      specificity, negative predictive value and positive predictive value of FSH
      relative to AMH for these women were 77.8%, 95.7%, 90.2% and 89.4%, respectively
      whereas the same values of AFC relative to AMH were 92.6%, 99.1 %, 96.6% and 98%,
      respectively. Conclusion: Women with menstrual irregularity and infertility are
      at a higher risk for satisfying criteria of poor ovarian response irrespective of
      age. A policy incorporating these surrogate markers can be used to screen these
      women for occult premature ovarian insufficiency.

PMID- 29201667
TI  - The Effects of Adjuvant Therapies on Embryo Transfer Success.
AB  - Background: Many adjuvant therapies are employed during IVF treatment in an
      attempt to improve outcomes. The objective of our study was to evaluate the
      impact of thirteen adjuvants (Intralipid, steroids, melatonin, coenzyme Q10,
      Filgrastim, testosterone, DHEA, growth hormone, antibiotics, hCG infusion,
      aspirin, enoxaparin/heparin and dopamine agonists) on the success of embryo
      transfers. Methods: This is a retrospective cohort study of all embryo transfers
      between January 2010 and April 2015 from a multi-site IVF clinic. To ensure data
      independence, random number was applied to each included transfer and used to
      pick an individual transfer for each patient (n=13,372). Outcomes were clinical
      pregnancy, live birth and pregnancy loss. Univariate comparison with Chi square
      testing and logistic regression analysis were used. The level of significance was
      p<0.05. Results: Steroid use was significantly associated with both reduced
      clinical pregnancy loss (aOR 0.39, CI 0.19-0.76) and improved live birth rates
      (aOR 1.40, CI 1.11-1.77). While aspirin was associated with improved live birth
      rates (aOR 1.48, CI 1.08-2.02), melatonin was linked with reduced rates (aOR
      0.66, CI 0.45-0.96). Analyses for all other adjuvant therapies did not reach
      statistical significance after logistic regression. Conclusion: Many of the
      interventions investigated in this study fail to significantly demonstrate any
      effects on the success of embryo transfers. Our analysis results show negative
      effects with the use of melatonin; however, use of aspirin or steroids
      demonstrated promising, potentially beneficial outcomes. Additional exploration
      is needed to guide evidence-based practice.

PMID- 29201668
TI  - Efficacy of Intrauterine Injection of Granulocyte Colony Stimulating Factor (G
      CSF) on Treatment of Unexplained Recurrent Miscarriage: A Pilot RCT Study.
AB  - Background: Endometrium undergoes several changes in structure and cellular
      composition during pregnancy. Granulocyte Colony-stimulating Factor (GCS-F) is an
      important cytokine with critical role in embryo implantation and pregnancy. The
      aim of the present study was to evaluate the impact of intrauterine injection of
      G-CSF in patients who suffer from unexplained recurrent miscarriage (RM).
      Methods: In the present randomized clinical trial, a total of 68 patients were
      randomly allocated into two study groups including intrauterine G-CSF (n=23, 300
      MUg) injection and control group (n=27, no G-CSF injection). Eighteen out of 68
      patients were excluded from the final analysis due to different reasons. All
      patients were in Ovulation Induction (I/O) cycle. In G-CSF group, intrauterine
      injection of G-CSF was done twice in the cycle. All enrolled patients were under
      40 years old and had at least two unexplained pregnancy losses. Pregnancy was
      evaluated by titer of betahCG, presence of gestational sac (implantation) and
      fetal heart rate (clinical pregnancy) was assessed by vaginal ultrasonography.
      Student's T test and Mann-Whitney U were used for analysis. The p<=0.05 was
      determined as statistically significant. Results: No significant differences were
      observed between the two study groups when the rates of chemical pregnancy (26.1%
      vs. 29.6%, p=0.781), implantation (26.1% vs. 22.2%, p=0.750), clinical pregnancy
      (17.4% vs. 11.1%, p=0.689) and abortion (33% vs. 37.5%, p=0.296) were compared.
      Conclusion: In our study, no significant difference was observed between the two
      study groups when the rates of chemical pregnancy, implantation, clinical
      pregnancy and abortion were compared.

PMID- 29201669
TI  - Comparison of Outcomes of IVF Cycles Between Transferred Frozen Thawed Embryos
      and Fresh Embryos by a 2 Year Survey.
AB  - Background: Infertility as one of most concerning topics in childbearing age
      mothers needs better managements with less complications and IVF can be assumed
      as an efficient method. This study aimed to compare pregnancy outcomes in fresh
      and frozen embryos transferred in IVF cycles. Methods: In a retrospective study,
      11201 patients underwent IVF cycles from 21st March 2013 to 20th March 2014 and
      they were categorized into two groups according to age, previous tubal disease
      and surgery, tubal ligation, and previous ectopic pregnancy variables. Clinical
      pregnancy, ectopic pregnancy, multiple pregnancy, spontaneous abortion and
      preterm labor rates were compared in both groups. Results: 11201 patients were
      categorized in two groups. Results of 4149 frozen-thawed embryo transfer cycles
      showed 1281 clinical pregnancies (30.9%) and 7052 fresh embryo transfer cycles
      which led to 2085 clinical pregnancies (29.6%) without significant differences
      between groups (p=0.14). Ectopic pregnancy rates in frozen and fresh groups were
      38 (3%) and 52 (2.5%), respectively (p=0.409). Spontaneous abortion rates in
      frozen and fresh groups were 8.4% and 9.4%, respectively (p=0.32). Preterm labor
      was seen in both frozen and fresh groups as 28.2% and 23.4%, respectively
      (p=0.002) and finally, multigestational pregnancy rate was 25.7% and 22.8% in
      frozen and fresh groups (p=0.06). Conclusion: According to this study, frozen and
      fresh embryo transfer cycles were not significantly different in clinical
      pregnancy, ectopic pregnancy, multigestational pregnancy rates, but preterm labor
      was dominant in frozen group, which should not be overlooked.

PMID- 29201670
TI  - Coexistent Circumvallate Placenta and Battledore Insertion of Umbilical Cord
      Resulting in Grave Obstetric Outcome: A Case Report.
AB  - Background: Various placental and cord abnormalities have been known to adversely
      affect the obstetric outcome. Circumvallate placenta and Battledore insertion of
      the umbilical cord are both rare and known to be associated with poor obstetric
      outcome individually. Case Presentation: In this case report, the woman presented
      at 8 months of gestation with preeclampsia with IUFD to North Easter Indira
      Gandhi Regional Institute of Health and Medical Science Shillong on 22/7/16 and
      delivered a macerated fetus vaginally. After delivery, examination revealed both
      a circumvallate placenta and Battledore insertion of umbilical cord. This might
      have attributed to preeclampsia and ultimately IUFD in this case as she had no
      other identifiable cause for IUFD. Conclusion: If such placental and cord
      abnormalities are suspected or diagnosed antenatally by ultrasonography, the
      pregnancy should be regarded as high risk. Such woman would require more
      stringent follow up in the antenatal period and continuous intrapartum monitoring
      to avoid any catastrophe and to achieve a favorable maternal and fetal outcome.

PMID- 29201671
TI  - Early Fertilization Abnormalities in the Human: An Exhausted Area of Research?

PMID- 29201672
TI  - ESICONs and Expectations by the Endocrine Society of India.

PMID- 29201673
TI  - The Next Steps...for IJEM.

PMID- 29201674
TI  - ESICON 2017.

PMID- 29201675
TI  - Prevalence and Risk Factors of Asymptomatic Gallstone Disease in North-East Part
      of Bangladesh.
AB  - Background: The study was designed to assess the prevalence of asymptomatic
      gallstone disease in North-East part of Bangladesh. Materials and methods:
      Randomly selected asymptomatic persons, unknown to have gallstone disease, from
      both rural and urban areas were enrolled. They were subjected to abdominal
      ultrasonography and findings were recorded in a data sheet. Results: Total 1,019
      persons (316 males and 703 females) were examined. Age of them varied from 18 to
      80 years with mean age of 37.22 years. Out of them, 61 (6%) persons were found to
      have gallstone. Among them, 14 were males and 47 were females. Both male and
      females of age below 40 years were more affected. Gallstone disease was found
      more commonly among housewives and middle class people. Among 61 patients with
      gallstone, seven were underweight (11.47%), 32 (52.45%) had normal weight and 22
      (36.06%) were overweight, obese or extremely obese. But, this difference was not
      statistically significant (p = 0.894). Conclusion: Prevalence of asymptomatic
      gallstone disease was found in 6% apparently healthy subjects of North-East part
      of Bangladesh. It was more prevalent among housewives and middle class group of
      population. It is also common among the people of age group below 40 years. How
      to cite this article: Saha M, Nahar K, Hosen MMA, Khan MH, Saha SK, Shil BC,
      Rahman MH. Prevalence and Risk Factors of Asymptomatic Gallstone Disease in North
      East Part of Bangladesh. Euroasian J Hepato-Gastroenterol 2015;5(1):1-3.

PMID- 29201676
TI  - Nonalcoholic Fatty Liver Disease: Study of Demographic and Predictive Factors.
AB  - Background: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of
      liver disease characterized by excess of fat in liver which ranges from simple
      steatosis to nonalcoholic steato-hepatitis (NASH), cirrhosis and hepatocellular
      carcinoma (HCC) in the absence of excessive alcohol consumption. Materials and
      methods: The study was carried out in 216 with serologically defined fatty liver.
      They underwent detailed history evaluation, clinical examination and
      anthropometric measurements, biochemical and serological tests. The cut-off
      values for central obesity were waist hip ratio (WHR) > 0.85 in women and > 0.9
      in men. Results: The prevalence of NAFLD was highest in the age group of 31 to 60
      years. It was more common in males than females. Twenty cases (11.7%) had
      discomfort at right upper abdomen. Hepatomegaly was found in 27 patients (13.2%),
      impaired glucose tolerance (IGT) in 29 (14.21%) and diabetes mellitus in 38
      (18.63%) patients. Overweight or obesity was found in 110 (53.92%) cases and
      central obesity was seen in 129 (63.23%) patients. Hence, metabolic syndrome
      (according to International Diabetes Federation Criteria) was present in 62.25%
      cases of NAFLD. Alanine aminotransferase (ALT) more than upper limit of normal
      was found in 36.76% cases. Conclusion: Risk factors for NAFLD in Bangladesh are
      similar to reported from the rest of the world. Age more than 30 years, male sex,
      WHR > 0.9 in men and more than 0.85 in female, BMI more than 25, glucose
      intolerance are predictive factors for NAFLD. How to cite this article: Shil BC,
      Saha M, Ahmed F, Dhar SC. Nonalcoholic Fatty Liver Disease: Study of Demographic
      and Predictive Factors. Euroasian J Hepato-Gastroenterol 2015;5(1):4-6.

PMID- 29201677
TI  - Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison
      between Indirect Immunofluorescence and Immunoperoxidase Method.
AB  - Background: Hepatitis B virus (HBV) infection has many faces. Precore and core
      promoter mutants resemble inactive carrier status. The identification of
      hepatitis B core antigen (HBcAg) in hepatocytes may have variable clinical
      significance. The present study was undertaken to detect HBcAg in chronic
      hepatitis B (CHB) patients and to assess the efficacy of detection system by
      indirect immunofluorescence (IIF) and indirect immunoperoxidase (IIP). Materials
      and methods: The study was done in 70 chronic HBV-infected patients. Out of 70
      patients, eight (11.4%) were hepatitis B e antigen (HBeAg) positive and 62
      (88.57%) were HBeAg negative. Hepatitis B core antigen was detected by indirect
      immunofluorescence (IIF) and indirect immunoperoxidase (IIP) methods in liver
      tissue. Results: All HBeAg positive patients expressed HBcAg by both IIF and IIP
      methods. Out of 62 patients with HBeAg-negative CHB, HBcAg was detected by IIF in
      55 (88.7%) patients and by IIP in 51 (82.26%) patients. A positive relation among
      viral load and HBcAg detection was also found. This was more evident in the case
      of HBeAg negative patients and showed a positive relation with HBV DNA levels.
      Conclusion: Hepatitis B core antigen can be detected using the IIF from formalin
      fixed paraffin block preparation and also by IIP method. This seems to reflect
      the magnitudes of HBV replication in CHB. How to cite this article: Raihan R,
      Tabassum S, Al-Mahtab M, Nessa A, Jahan M, Kabir CMS, Kamal M, Aguilar JC.
      Hepatitis B Core Antigen in Hepatocytes of Chronic Hepatitis B: Comparison
      between Indirect Immunofluorescence and Immunoperoxidase Method. Euroasian J
      Hepato-Gastroenterol 2015;5(1):7-10.

PMID- 29201678
TI  - Evaluation of a Rapid One-step Real-time PCR Method as a High-throughput
      Screening for Quantification of Hepatitis B Virus DNA in a Resource-limited
      Setting.
AB  - : Virological monitoring is the best predictor for the management of chronic
      hepatitis B virus (HBV) infections. Consequently, it is important to use the most
      efficient, rapid and cost-effective testing systems for HBV DNA quantification.
      The present study compared the performance characteristics of a one-step HBV
      polymerase chain reaction (PCR) vs the two-step HBV PCR method for quantification
      of HBV DNA from clinical samples. A total of 100 samples consisting of 85
      randomly selected samples from patients with chronic hepatitis B (CHB) and 15
      samples from apparently healthy individuals were enrolled in this study. Of the
      85 CHB clinical samples tested, HBV DNA was detected from 81% samples by one-step
      PCR method with median HBV DNA viral load (VL) of 7.50 * 103 lU/ml. In contrast,
      72% samples were detected by the two-step PCR system with median HBV DNA of 3.71
      * 103 lU/ml. The one-step method showed strong linear correlation with two-step
      PCR method (r = 0.89; p < 0.0001). Both methods showed good agreement at Bland
      Altman plot, with a mean difference of 0.61 log10 IU/ml and limits of agreement
      of -1.82 to 3.03 log10 IU/ml. The intra-assay and interassay coefficients of
      variation (CV%) of plasma samples (4-7 log10 IU/ml) for the one-step PCR method
      ranged between 0.33 to 0.59 and 0.28 to 0.48 respectively, thus demonstrating a
      high level of concordance between the two methods. Moreover, elimination of the
      DNA extraction step in the one-step PCR kit allowed time-efficient and
      significant labor and cost savings for the quantification of HBV DNA in a
      resource limited setting. How to cite this article: Rashed-Ul Islam SM, Jahan M,
      Tabassum S. Evaluation of a Rapid One-step Real-time PCR Method as a High
      throughput Screening for Quantification of Hepatitis B Virus DNA in a Resource
      limited Setting. Euroasian J Hepato-Gastroenterol 2015;5(1):11-15.

PMID- 29201679
TI  - The Value of Serum CA19-9 Levels in predicting Extent of Hepatic Fibrosis in
      Patients with Chronic Hepatitis B.
AB  - : This cross-sectional observational study was conducted to evaluate the
      implication of CA19-9 level in predicting the extent of hepatic fibrosis in
      patients with chronic hepatitis B (CHB). Fifty treatment-naive patients with CHB
      were divided into three groups: group I, patients with no fibrosis (F0; n = 3);
      group II, patients with mild fibrosis (F1; n = 25) and group III, patients with
      moderate fibrosis (F3; n = 22). There was no significant (p > 0.05) difference in
      levels of serum bilirubin, serum alanine aminotransferase, alkaline phosphatase,
      and alpha fetoprotein among groups I, II and III. Also, mean CA19-9 level did not
      differ among the three groups. It was observed that, for group II, AUC was 42.6%,
      sensitivity 52%, specificity 32%, considering cut-off value as 2.8 U/ml to
      predict F1 liver fibrosis. For group III, AUC was 57.7%, sensitivity 68%,
      specificity 50% considering cut-off value as 3.2 U/ml to predict F3 fibrosis. The
      levels of CA19-9 level do not seem to have significant predictive implication to
      assess hepatic fibrosis. How to cite this article: Haque MS, Sultana S, Al-Mahtab
      M, Al-Mamun A, Rahman S. The Value of Serum CA19-9 Levels in predicting Extent of
      Hepatic Fibrosis in Patients with Chronic Hepatitis B. Euroasian J Hepato
      Gastroenterol 2015;5(1):16-18.

PMID- 29201680
TI  - Current Concepts in Hepatocellular Carcinoma and Liver Transplantation: A Review
      and 2014 Update.
AB  - : Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide.
      Multiple treatment modalities for HCC are available, depending on size and number
      of tumor. Liver transplantation offers the most reasonable option for curative
      treatment, because it simultaneously removes the burden of the diseased liver.
      The Milan criteria currently remain the benchmark for the selection of patients
      with HCC for transplantation. However, there is considerable and promising
      interest in expanding the eligibility criteria to include the University of
      California San Francisco criteria. Liver transplantation (LT) has progressed
      during the past decade. The introduction of living donor LT has provided a means
      of expanding organ transplant, but with some inherent concerns. Herein, we
      reviewed the diagnosis and management of HCC with emphasis on the current
      concepts of liver transplantation for the treatment of HCC. How to cite this
      article: Ofosu A, Gurakar A. Current Concepts in Hepatocellular Carcinoma and
      Liver Transplantation: A Review and 2014 Update. Euroasian J Hepato-Gastroenterol
      2015;5(1):19-25.

PMID- 29201682
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in Cambodia.
AB  - : In Cambodia, the true burden of viral hepatitis has not been revealed, but many
      surveys were carried out focusing on specific population or on small scales.
      Different markers of viral hepatitis were found between 27 and 97% in children
      and almost 100% in adults. Viral hepatitis B in children was 3.5% in 2006 and
      dropped in 2011; and in adults, it ranged from 4.5 to 10.8%. Viral hepatitis C
      was between 0.87 and 14.7%. No data are available for hepatitis D in the country.
      Viral hepatitis E (anti-HEV IgG) went from 7.2 to 12.7%. The complications due to
      viral hepatitis including chronic liver diseases and hepatocellular carcinoma
      were reported in the health information system. Around 79% of the patients with
      high transaminase had at least one viral marker and about 45% of the adults with
      chronic hepatitis and liver cirrhosis were positive for Hepatitis B surface
      antigen (HBsAg). Hepatocellular carcinoma accounted for 19.1% of all reported
      cancer cases. Hepatitis B surface antigen was found in between 55 and 90% in
      adults with hepatocellular carcinoma and anti-HCV in one-fourth. The only
      intervention implemented in Cambodia is vaccination against viral hepatitis B
      (HepB vaccine). How to cite this article: Sreng B, Kimcheng HOK, Sovann LY, Huot
      ENG. Epidemiology of Viral Hepatitis and Liver Diseases in Cambodia. Euroasian J
      Hepato-Gastroenterol 2015;5(1):30-33.

PMID- 29201681
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in Bangladesh.
AB  - : Bangladesh is a South Asian country with a homogeneous population. However,
      some difference has been demonstrated in the distribution of liver disease in
      different parts of the country. Hepatitis E remains the principal cause of acute
      hepatitis in Bangladesh, while chronic liver disease in Bangladesh, including
      hepatocelullar carcinoma, is predominantly due to hepatitis B virus. Hepatitis B
      has been extensively studied and characterized in Bangladesh, and some major
      clinical trials with HBV-related antigens have also been conducted. How to cite
      this article: Al-Mahtab M. Epidemiology of Viral Hepatitis and Liver Diseases in
      Bangladesh. Euroasian J Hepato-Gastroenterol 2015;5(1):26-29.

PMID- 29201683
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in India.
AB  - : Diverse Indian population provides an excellent opportunity to study the
      prevalence and feature of hepatitis virus for understanding viral evaluation and
      viral pathogenesis. India is in intermediate zone of pathogenesis of hepatitis B
      (2-5%), and India is having around 40 million hepatitis B virus (HBV) carriers. A
      wide variation in prevalence of hepatitis B is observed from region to region and
      community to community. The prevalence of HBV is higher among tribal population,
      than nontribal. Population prevalence of hepatitis C virus (HCV) infection in
      India is 1%. Prevalence study among blood donors may reflect population
      prevalence. Hemodialysis increases the possibility of blood borne viral
      infection. Higher prevalence of HBV among tribal population is of paramount
      importance from public health point of view and hepatitis B vaccination. How to
      cite this article: Bhaumik P. Epidemiology of Viral Hepatitis and Liver Diseases
      in India. Euroasian J Hepato-Gastroenterol 2015;5(1):34-36.

PMID- 29201684
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in Mongolia.
AB  - : Mongolia which is located in Northern Asia between Russia and China is endowed
      with one of lowest population density in the world. Acute hepatitis due all types
      of hepatitis virus has been reported in Mongolia. Also, dual and triple hepatitis
      viruses, HBV, HDV and HCV are highly prevalent among patients with chronic liver
      disease living in Mongolia. Due to these facts, liver cancer is the leading cause
      of cancer mortality in Mongolia. The national immunization program including
      vaccination against hepatitis B was started in 1991 and screening of blood
      donations for HBsAg and anti-HCV was introduced in 1993 and 1997 respectively.
      The incidence of hepatitis viruses showing a downhill course in some parts of
      Mongolia, but comprehensive efforts are needed to control hepatitis viruses and
      containment of hepatitis related liver diseases and liver cancer in Mongolia. How
      to cite this article: Tsatsralt OB. Epidemiology of Viral Hepatitis and Liver
      Diseases in Mongolia. Euroasian J Hepato-Gastroenterol 2015;5(1):37-39.

PMID- 29201685
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in Nepal.
AB  - : Geographical and ethnic diversity in Nepal has led to interesting epidemiology
      of viral hepatitis and liver diseases. Before the epidemic of Biratnagar that
      occurred in April to June 2014, Kathmandu was the only known endemic region for
      hepatitis E virus infection (HEV), where at least four previous epidemics have
      been documented since 1973. Due to rapid urbanization with still low
      socioeconomic condition, other major cities are appreciated to be at increasing
      risk of outbreaks. Characteristics of HEV epidemics and genetic changes of HEV
      during last decade have been studied. While hepatitis A virus infection was only
      common during childhood till recent years, it is re-emerging as an important
      etiology of acute hepatitis in young adults. Nepal is classified as low endemic
      region for hepatitis B virus infection (HBV) with overall seroprevalence of 1.1%.
      But, some ethnic groups and geographical areas have high prevalence rates.
      Despite low endemicity, HBV accounts for majority of cases of hepatocellular
      carcinoma and liver cirrhosis in the country. Similarly, though hepatitis C virus
      (HCV) is present in only 0.4% of general population, high seroprevalence was
      found among intravenous drug abusers many of them with HIV coinfection. Apart
      from hepatitis viruses, alcohol use also contributes significantly to liver
      cirrhosis and chronic liver failure. A unique form of hepatic venous outflow
      obstruction called 'hepatic vena cava syndrome' has been identified as an
      important etiology of liver cirrhosis and hepatocellular carcinoma. How to cite
      this article: Shrestha A. Epidemiology of Viral Hepatitis and Liver Diseases in
      Nepal. Euroasian J Hepato-Gastroenterol 2015;5(1):40-42.

PMID- 29201686
TI  - Epidemiology of Viral Hepatitis and Liver Diseases in Pakistan.
AB  - : Pakistan is among ten most populous countries in world. All sorts of hepatitis
      are highly prevalent in Pakistan. Due to lack of proper mechanisms to handle
      sewerage, disinfection and lack of clean water supply across the country,
      hepatitis A and E are endemic in Pakistan. Moreover, Pakistan ranked in
      intermediate prevalence zone for hepatitis B and C. Also, prevailing
      socioeconomic conditions, political statuses and unstable healthcare delivery
      system are not suitable for tackling further progression of hepatitis viruses and
      its complications. The notable factors related to epidemiology of different
      hepatitis viruses have been described in this communication. How to cite this
      article: Butt AS. Epidemiology of Viral Hepatitis and Liver Diseases in Pakistan.
      Euroasian J Hepato-Gastroenterol 2015;5(1):43-48.

PMID- 29201687
TI  - Epidemiology of Hepatitis B and C Virus Infections and Liver Cancer in Vietnam.
AB  - : Vietnam has been a highly endemic country of hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infections with high hepatitis B surface antigen (HBsAg)
      rate (8.8-19.0%) and high anti-HCV rate (1.0-3.3%) among general population. High
      mortality rates of liver cancer were also estimated from 14.8 to 23.7 per
      100,000. Recently, the coverage of universal HB vaccination for infants has not
      been high as expected while there have been no other national programs against
      HBV and HCV infections yet. The burden of HBV and HCV-related diseases is
      predicted to remain a significant health problem in next decade. How to cite this
      article: Do SH. Epidemiology of Hepatitis B and C Virus Infections and Liver
      Cancer in Vietnam. Euroasian J Hepato-Gastroenterol 2015;5(1):49-51.

PMID- 29201688
TI  - A Case of Acute Pancreatitis developing after Extracorporeal Shock Wave
      Lithotripsy.
AB  - : Extracorporeal shock wave lithotripsy (ESWL) is a standard treatment method
      used for the treatment of renal calculi and upper ureteral calculi. Acute
      pancreatitis is a serious condition which develops due to multiple etiologic
      factors and is characterized by autodigestion of the pancreas. A case of acute
      pancreatitis which developed following ESWL performed for right renal calculi
      treatment is presented here. How to cite this article: Goral V, Sahin E, Arslan
      M. A Case of Acute Pancreatitis developing after Extracorporeal Shock Wave
      Lithotripsy. Euroasian J Hepato-Gastroenterol 2015;5(1):52-54.

PMID- 29201689
TI  - A Case Report of Decompensated Cirrhosis of Liver with Sideroblastic Anemia.
AB  - : A 35-year-old man was admitted to hospital with severe anemia. Two years back,
      he had presented with bleeding esophageal varices and subsequently diagnosed as a
      case of chronic liver disease with portal hypertension. He was then treated with
      esophageal band ligation. He tested positive for hepatitis B surface antigen with
      HBV DNA levels of 4 * 106 copies/ml by PCR. His repeat endoscopy showed grade 1
      esophageal varices with no evidence of recent or active bleeding. On further
      investigation, his bone marrow showed dimorphic erythroid hyperplasia with ring
      sideroblasts and diagnosis of sideroblastic anemia was made. Although rarely, it
      was suggested that as cirrhosis is a chronic process, it may cause nutritional
      deficiency, which in turn may lead to the development of anemia. How to cite this
      article: Al-Mahtab M, Rahim A, Noor-e-Alam SM, Khandokar FA, LutfulMubin A,
      Rahman S. A Case Report of Decompensated Cirrhosis of Liver with Sideroblastic
      Anemia. Euroasian J Hepato-Gastroenterol 2015;5(1):55-56.

PMID- 29201690
TI  - Abdominal Tuberculosis: A Diagnostic Dilemma.
AB  - : According to the World Health Organization, more than 2 billion people are
      estimated to be infected with tuberculosis (TB) and approximately 95% of
      tuberculosis cases occur in developing countries. Extrapulmonary forms of
      tuberculosis constitute approximately one-sixth of all cases and the prevalence
      of extrapulmonary tuberculosis (TB) seems to be rising, particularly due to
      increasing prevalence of acquired immunodeficiency syndrome (AIDS). In patients
      with extrapulmonary TB, abdomen is involved in 12% of patients. Gastrointestinal
      involvement is found in 66 to 75% of abdominal cases, with the terminal ileum and
      the ileocecal region being the most common sites of involvement. Here, we report
      a case of abdominal TB. How to cite this article: Tarafder AJ, Al-Mahtab M, Das
      SR, Karim R, Rahaman H, Rahman S. Abdominal Tuberculosis: A Diagnostic Dilemma.
      Euroasian J Hepato-Gastroenterol 2015;5(1):57-59.

PMID- 29201691
TI  - Epstein-Barr Virus and Cytomegalovirus induced Acute Hepatitis in Young Female
      Patient.
AB  - : Acute hepatitis is a disorder that goes with liver cell necrosis and liver
      inflammation. Among the causes of acute hepatitis, the most common reasons are
      viral hepatitis. About 95% of the acute hepatitis generate because of
      hepatotropic viruses. Epstein-barr virus (EBV) and cytomegalovirus (CMV) are from
      the family of herpes viruses and rare causes of acute hepatitis. In this case
      report, acute hepatitis due to EBV and CMV coinfection will be described. How to
      cite this article: Ates I, Kaplan M, Yilmaz N, Ciftci F. Epstein-Barr Virus and
      Cytomegalovirus induced Acute Hepatitis in Young Female Patient. Euroasian J
      Hepato-Gastroenterol 2015;5(1):60-61.

PMID- 29201692
TI  - Brain Death after Liver Transplantation for Fulminant Hepatic Failure: A Report
      of Two Cases.
AB  - : Cerebral injury may persist and brain death may occur following an emergency
      liver transplantation (LT) for fulminant hepatic failure (FHF) even if the graft
      functions well. We herein present two patients developing brain death following
      emergency LT for FHF. How to cite this article: Akoglu M, Surmelioglu A, Ozer I,
      Ercan M, Ulas M, Akdogan M, Bostanci EB. Brain Death after Liver Transplantation
      for Fulminant Hepatic Failure: A Report of Two Cases. Euroasian J Hepato
      Gastroenterol 2015;5(1):62-64.

PMID- 29201693
TI  - Complicated Hydatid Cyst: Ultrasonographic Illusion and Endoscopic Diagnosis.
AB  - : Liver cyst hydatic (LCH) is an important parasitic disease caused by
      Echinococcus spp. Rupture of the biliary tract is an important and serious
      complication. It is often diagnosed on a suspicious clinical findings by
      radiologic imaging procedures. But, complicated hydatid cyst disease can show
      different radiological images, as they can simulate any disease. Here, we
      reported a case which diagnosed cholangiocellular carcinoma in primary diagnosis
      by ultrasonographic evaluation but diagnosed hydatid cyst in endoscopy
      evaluation. A 30-year-old female patient was admitted to the hospital with 1 year
      continuous severe abdominal pain aggravated for 1 month. How to cite this
      article: Kefeli A, Basyigit S, Yeniova AO, Nazligul Y. Complicated Hydatid Cyst:
      Ultrasonographic Illusion and Endoscopic Diagnosis. Euroasian J Hepato
      Gastroenterol 2015;5(1):65-66.

PMID- 29201694
TI  - Editorial.

PMID- 29201695
TI  - Recording and Analysis of Bowel Sounds.
AB  - Background: The aim of this study was to construct an electronic bowel sound
      recording system and determine its usefulness for the diagnosis of appendicitis,
      mechanical ileus and diffuse peritonitis. Materials and methods: A group of 67
      subjects aged 17 to 88 years including 15 controls was examined. Bowel sounds
      were recorded using an electret microphone placed on the right side of the
      hypogastrium and connected to a laptop computer. The method of adjustable grids
      (converted into binary matrices) was used for bowel sounds analysis. Results:
      Significantly, fewer (p <= 0.05) sounds were found in the mechanical ileus
      (1004.4) and diffuse peritonitis (466.3) groups than in the controls (2179.3).
      After superimposing adjustable binary matrices on combined sounds (interval
      between sounds <0.01 s), significant relationships (p <= 0.05) were found between
      particular positions in the matrices (row-column) and the patient groups. These
      included the A1_T1 and A1_T2 positions and mechanical ileus as well as the A1_T2
      and A1_T4 positions and appendicitis. For diffuse peritonitis, significant
      positions were A5_T4 and A1_T4. Conclusion: Differences were noted in the number
      of sounds and binary matrices in the groups of patients with acute abdominal
      diseases. Certain features of bowel sounds characteristic of individual abdominal
      diseases were indicated. List of abbreviations: BS: bowel sound; APP:
      appendicitis; IL: mechanical ileus; PE: diffuse peritonitis; CG: control group;
      NSI: number of sound impulses; NCI: number of combined sound impulses; MBS: mean
      bit-similarity; TMIN: minimum time between impulses; TMAX: maximum time between
      impulses; TMEAN: mean time between impulses. How to cite this article: Zaborski
      D, Halczak M, Grzesiak W, Modrzejewski A. Recording and Analysis of Bowel Sounds.
      Euroasian J Hepato-Gastroenterol 2015;5(2):67-73.

PMID- 29201696
TI  - Expressions of TIMP-1, COX-2 and MMP-7 in Colon Polyp and Colon Cancer.
AB  - Objective: We aimed to investigate the relationship of expression of matrix
      metalloproteinase-7 (MMP-7), tissue inhibitor of metalloproteinase-1 (TIMP-1) and
      cyclooxygenase-2 (COX-2) in colon cancer and its predecessor colon polyp.
      Materials and methods: This study included 29 patients with colon polyp, 19
      patients with colon cancer and 65 healthy control subjects. The expressions of
      MMP-7, TIMP-1 and COX-2 were investigated by real time-polymerase chain reaction
      (RT-PCR). Results: The expressions of TIMP-1, COX-2 and MMP-7 levels were
      significantly higher in polyp tissue compared to normal tissue (p = 0.024, p <
      0.001, p = 0.009, respectively). Expression of TIMP-1, COX-2 and MMP-7 in cancer
      tissues were higher than both normal tissue and polyp tissue (p = 0.009 and p =
      0.001; p < 0.001 and p < 0.001; p = 0.029 and p = 0.008, respectively). In the
      cancer group, no significant relationship was detected between metastasis and MMP
      7, TIMP-1 and COX-2 expressions (p > 0.05). In the polyp tissues, no significant
      relationship was detected between the histologic type and size of polyps and MMP
      7, TIMP-1 and COX-2 levels (p > 0.05). The areas under the receiver operating
      characteristic (ROC) curve for the cancer group were 0.821 for TIMP-1, 0.888 for
      COX-2, and 0.880 for MMP-7 (p = 0 < 0.001). Conclusion: A role and implication of
      expressions of MMP-7, COX-2 and TIMP-1 in colon cancer is predicted. How to cite
      this article: Bengi G, Keles D, Topalak O, Yalcin M, Kiyak R, Oktay G.
      Expressions of TIMP-1, COX-2 and MMP-7 in Colon Polyp and Colon Cancer. Euroasian
      J Hepato-Gastroenterol 2015;5(2):74-79.

PMID- 29201697
TI  - Liver Transplantation in Cases with Acute Liver Failure.
AB  - Background: Acute liver failure (ALF) is a rare, life-threatening clinical
      condition that is characterized by severe hepatocellular necrosis, jaundice,
      coagulopathy and encephalopathy. The aim of this study was to evaluate patients
      who underwent liver transplantation at Dokuz Eylul University of Medicine Faculty
      (DEUMF) due to ALF. Materials and methods: The patients who underwent liver
      transplantation at DEUMF due to ALF were evaluated retrospectively. Results: All
      of the liver transplantations performed in this study were successful; toxicity
      was the major cause of ALF in these patients (84%). Conclusion: Results of this
      study may not be generalizable to all of Turkey since the patients included in
      this study were only from one region. However, our study is in accordance with
      others that show that liver transplantation is a very safe and effective method
      for the treatment of ALF. How to cite this article: Yalcin M, BengI G, Akarsu M,
      Inek T, Astarcioslu I. Liver Transplantation in Cases with Acute Liver Failure.
      Euroasian J Hepato-Gastroenterol 2015;5(2):80-82.

PMID- 29201698
TI  - Drug-induced Liver Disease in Patients with Diabetes Mellitus.
AB  - : The study presented here was accomplished to assess the course of drug-induced
      liver diseases in patient's rheumatoid arthritis receiving long-term methotrexate
      therapy. Diabetes mellitus was revealed as the most significant risk factor. The
      combination of diabetes mellitus with other risk factors (female sex) resulted in
      increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of
      hepatic functions. The effectiveness and safety of ursodeoxycholic acid and
      cytolytic type-with S-Adenosyl methionine was also evaluated. Abbreviations: 13C
      MBT: 13C-methacetin breath test; ALT: alanine aminotransferase; AP: alkaline
      phosphatase; AST: aspartic transaminase; DILD: drug-induced liver disease; DM:
      diabetes mellitus; HE: hepatic encephalopathy; HFM: hepatic functional mass;
      SAMe: S-Adenosyl methionine; UDCA: ursodeoxycholic acid. How to cite this
      article: Iryna K, Helen M, Elena S. Drug-induced Liver Disease in Patients with
      Diabetes Mellitus. Euroasian J Hepato-Gastroenterol 2015;5(2):83-86.

PMID- 29201699
TI  - Hyperbilirubinemia as a Diagnostic Tool for the Prediction of Appendicular
      Perforation: A Prospective Study.
AB  - Background: The certainty of diagnosing acute appendicitis in patients presenting
      with right iliac fossa pain still remains a mystery though acute appendicitis
      being the commonest surgical procedure done in emergency. In acute appendicitis,
      serum bilirubin levels are raised due to hepatocellular damage as a result of
      direct insult caused by Gram-negative bacterial endotoxemia. The need for the
      study is to conclude whether the serum bilirubin can be considered as a new
      laboratory marker to aid in the diagnosis of acute appendicitis and if so, does
      it have the predictive capacity to warn us about appendicular perforation.
      Materials and methods: This is a prospective study carried out at rural tertiary
      healthcare center and includes 213 patients clinically diagnosed as acute
      appendicitis. Results: Out of 213 patients, raised serum bilirubin >=1.2 mg/dl
      was present in 195 (91.5%) patients, out of which 194 (99.4%) patients had
      histopathologically inflamed appendix and this difference was statistically
      highly significant with p-value < 0.0001. In this study, 32 patients had
      perforated appendix. Out of those, 30 patients had bilirubin >= 4 mg/dl and 2
      patients had bilirubin level between 1.2 and < 4 mg/dl. Raised serum bilirubin
      (>=4 mg/dl) was present in 35 (17.9%) patients, out of which 30 (87.7%) patients
      had perforated appendix. How to cite this article: Saxena D, Tandon M, Shah Y,
      Gedam BS. Hyperbilirubinemia as a Diagnostic Tool for the Prediction of
      Appendicular Perforation: A Prospective Study. Euroasian J Hepato-Gastroenterol
      2015;5(2):87-89.

PMID- 29201700
TI  - Prevalence and Impact of Hepatitis on the Quality of Life of Patients.
AB  - Background: Hepatitis is a disorder which is emerging as major health problem
      with increasing morbidity and mortality. Inappropriate management of this disease
      leads to several complications that can impair the health related quality of life
      (HRQoL) of the individuals. There, we designed this study to assess the HRQoL in
      patients suffering from hepatitis. Materials and methods: This prospective,
      observational study was conducted for 2 months in patients with hepatitis. All
      patients with hepatitis were recruited in the study after giving written informed
      consent. The participants were given both World Health Organization Quality of
      Life-Bref (WHO QoL-Bref) and short form (SF-36) health survey questionnaires for
      assessing the quality of life (QoL) of patients. The participants were given
      counseling of lifestyle modification and underwent a thorough medical examination
      and a detailed history was taken. Results: A total of 65 volunteers participated
      in the study, out of which 30 were control and 35 were patients suffering from
      hepatitis; hepatitis C was found to be more prevalent. The patients with
      hepatitis had a significantly poor QoL as compared to control. In hepatitis
      patients, physical health and physical functioning was better in males as
      compared to females. Social relationships were also good in males than females.
      But females had higher score in role limitation due to physical health, emotional
      wellbeing, social functioning, pain, general health as per SF-36 scores but it
      was not statistically significant. Conclusion: Hepatitis affected the HRQoL in
      Indian population and parameters seem to be heterogeneously affected in males and
      females. How to cite this article: Mittal P, Matreja PS, Rao HK, Khanna PML.
      Prevalence and Impact of Hepatitis on the Quality of Life of Patients. Euroasian
      J Hepato-Gastroenterol 2015;5(2):90-94.

PMID- 29201701
TI  - Seroprevalence of Hepatitis A Virus Antibodies among the Patients with Chronic
      Hepatitis B in Turkey.
AB  - Background: Hepatitis A virus (HAV) can cause significant pathology in patients
      with chronic hepatitis B virus (HBV), however, HAV can be prevented by
      vaccination. The aim of this study was to determine the implication of
      vaccination against HAV vaccine in patients with chronic hepatitis B. Materials
      and methods: The seroprevalence of anti-HAV IgG antibodies was investigated in
      the patients with chronic hepatitis B. Anti-HAV IgG antibodies were detected by
      commercially available ELISA kit. Results: A total of 673 patients (354 males,
      319 females with age range of 17-78 years) with chronic hepatitis B were included
      the study. Hepatitis A virus seropositivity rate was 34% in the patients younger
      than 20 years, 79% in the age group of 20 to 29 years, and 100% after 35 years of
      age. Discussion: Hepatitis A virus vaccination may be recommended for young adult
      patients with chronic hepatitis B in Turkey. How to cite this article: Tulek N,
      Ozsoy M, Moroglu C, Sonmezer MC, Temocin F, Ertem GT, Erdinc FS. Seroprevalence
      of Hepatitis A Virus Antibodies among the Patients with Chronic Hepatitis B in
      Turkey. Euroasian J Hepato-Gastroenterol 2015;5(2):95-97.

PMID- 29201703
TI  - Autoimmune Hepatitis with Distal Renal Tubular Acidosis and Small Bowel Partial
      Malrotation.
AB  - : Renal tubular acidosis (RTA) is not uncommon in patient with chronic autoimmune
      hepatitis (AIH), but usually remains latent. Here, we report a case of renal
      tubular acidosis RTA who presented with AIH. She was also diagnosed to have
      partial bowel malrotation. A 9-year-old girl, a case of distal RTA, presented
      with jaundice, abdominal distension and altered sensorium. She was diagnosed to
      be AIH, which was successfully treated with steroids and azathioprine. Coexistent
      midgut partial malrotation with volvulus was diagnosed during the treatment. She
      was treated successfully with anti-tuberculous treatment for cervical
      lymphadenitis. Autoimmune hepatitis should not be ruled out in each case of RTA
      presenting with jaundice. How to cite this article: Modi TK, Parikh H, Sadalge A,
      Gupte A, Bhatt P, Shukla A. Autoimmune Hepatitis with Distal Renal Tubular
      Acidosis and Small Bowel Partial Malrotation. Euroasian J Hepato-Gastroenterol
      2015;5(2):107-109.

PMID- 29201702
TI  - Liver Transplantation Update: 2014.
AB  - : The first liver transplantation (LT) was performed by Thomas E Starzl five
      decades ago, and yet it remains the only therapeutic option offering gold
      standard treatment for end-stage liver disease (ESLD) and acute liver failure
      (ALF) and certain early-stage liver tumors. Post-liver transplantation survival
      has also dramatically improved over the last few decades despite increasing donor
      and recipient age and more frequent use of marginal organs to overcome the organ
      shortage. Currently, the overall 1 year survival following LT in the United
      States is reported as 85 to 90%, while the 10 years survival rate is ~50%
      (http://www.unos.org). The improvements are mainly due to progress in surgical
      techniques, postoperative intensive care, and the advent of new immunosuppressive
      agents. There are a number of factors that influence the outcomes prior to
      transplantation. Since 2002, the model for end-stage liver disease (MELD) score
      has been considered a predicting variable. It has been used to prioritize
      patients on the transplant waiting list and is currently the standard method used
      to assess severity in all etiologies of cirrhosis. Hepatocellular carcinoma (HCC)
      is the most common standard MELD exception because the MELD does not necessarily
      reflect the medical urgency of patients with HCC. The criteria for candidates
      with HCC for receiving LT have evolved over the past decade. Now, patients with
      HCC who do not meet the traditional Milan (MC) or UCSF criteria for LT often
      undergo downstaging therapy I an effort to shrink the tumor size. The shortage of
      donor organs is a universal problem. In some countries, the development of a
      deceased organ donation program has been prevented due to socioeconomic,
      cultural, legal and other factors. Due to the shortage of cadaveric donors,
      several innovative techniques have been developed to expand the organ donor pool,
      such as split liver grafts, marginal- or extended-criteria donors, live donor
      liver transplantation (LDLT), and the use of organs donated after cardiac death.
      Herein, we briefly summarize recent advances in knowledge related to LT. We also
      report common causes of death after liver transplant, including the recurrence of
      hepatitis C virus (HCV) and its management, and coronary artery disease (CAD),
      including the role of the cardiac calcium score in identifying occult CAD. How to
      cite this article: Dogan S, Gurakar A. Liver Transplantation Update: 2014.
      Euroasian J Hepato-Gastroenterol 2015;5(2):98-106.

PMID- 29201704
TI  - Obstructed Umbilical Hernia: A Normal Presentation with Abnormal Contents.
AB  - : Umbilical hernia is a common problem encountered in children. The rarity of
      finding cecum and appendix is probably due to the fact that the appendix is
      seldom found in the proximity of the umbilicus. It would, therefore, appear
      worthwhile to report the occurrence of cecum and an inflamed appendix with Ladd's
      bands in an umbilical hernia of a child. The last case with similar presentation
      was presented in 1950s. How to cite this article: Agrawal VP, Shetty NS,
      Narasimhaprasad A. Obstructed Umbilical Hernia: A Normal Presentation with
      Abnormal Contents. Euroasian J Hepato-Gastroenterol 2015;5(2):110-111.

PMID- 29201706
TI  - A Case Report of Ulcerative Colitis Induced by Therapy of Colorectal Carcinoma.
AB  - : Although patients with ulcerative colitis have an increased risk for colon
      cancer which is associated with disease activity, location of involvement or the
      accompanying primary sclerosing cholangitis, ulcerative colitis induced by
      resections for colorectal carcinoma or chemotherapy drugs are very rare as case
      presentations in the literature. Fifty-nine year-old female patient with the
      diagnosis of sigmoid colon carcinoma have been developed ulcerative colitis 2
      months after low anterior resection and oral capecitabine treatment. Development
      of colitis after colon cancer may be associated with some causes as mutual
      genetic factors that take part at the pathophysiological mechanisms liable from
      occurrence of ulcerative colitis and colorectal carcinoma, chemotherapy agents,
      perioperative stress and underlying silent ulcerative colitis. It is unclear
      which role is certain. Increasing reports like this case will be useful in
      resolving this issue. How to cite this article: Temel T, Ozgenel SM, Canaz F,
      Arik D, Tokmak S, Ozakyol AH. A Case Report of Ulcerative Colitis Induced by
      Therapy of Colorectal Carcinoma. Euroasian J Hepato-Gastroenterol 2015;5(2):115
      117.

PMID- 29201705
TI  - Hepatitis B Virus Reactivation under Treatment with Nilotinib.
AB  - : Hepatitis B virus (HBV) reactivation with imatinib, a tyrosine kinase
      inhibitor, has been reported in chronic myeloid leukemia. Nilotinib is a more
      potent second generation tyrosine kinase inhibitor and it inhibits the Src-family
      kinase LCK and hamper proliferation and function of CD8 (+) T lymphocytes. CD8
      (+) T lymphocytes are the main cellular subset responsible for viral clearance in
      patients with HBV infection. We report a case of HBV reactivation under treatment
      with nilotinib. Fatal HBV reactivation is not usually related to death in chronic
      myeloid leukemia patients who have an expectation of longevity with well
      tolerated oral drugs. Thus, screening for latent chronic HBV infections including
      assessment of hepatitis B surface antigen (HBsAg), antibody to hepatitis B core
      antigen (anti-HBc antibody) and antibody to hepatitis B surface antigen (anti
      HBs), especially at countries with intermediate and high prevalence of HBsAg is
      warranted. Treatment with nucleoside analogs and close monitoring may be life
      saving in this context. How to cite this article: Temel T, Gunduz E, Sadigova E,
      Teke HU, Ozgenel SM, Ozakyol AH. Hepatitis B Virus Reactivation under Treatment
      with Nilotinib. Euroasian J Hepato-Gastroenterol 2015;5(2):112-114.

PMID- 29201707
TI  - A Rare Variant of Pancreatic Sarcoidosis: Diagnostic Challenge.
AB  - : Pancreatic sarcoidosis is one of the variant of systemic sarcoidosis which is
      extremely rare in literature and opined as an enigma. Hence, its diagnosis is
      very challenging as its presentation mimics pancreatic carcinoma. In view of a
      better understanding, we are presenting a case of pancreatic sarcoidosis to
      emphasize the above. To clearly distinguish sarcoidosis from malignancy, repeated
      computed tomography scans, Positron emission tomography scans, fine needle
      aspiration cytology, endoscopic retrograde cholangio-pancreatography supplemented
      with histology and relevant blood tests proved it to be a pancreatic sarcoidosis
      then a malignancy. Over the course, concrete evidence was divulged from lymph
      node biopsy and histology in clinching the diagnosis which later transformed into
      a malignancy. Therefore, we concluded it is a rare variant of pancreatic
      sarcoidosis and careful serial investigations include repeated imaging, histology
      and blood tests are essential to establish and most importantly differentiate the
      diagnosis. How to cite this article: Khangura T, Uddin G, Davies A, Keating J. A
      Rare Variant of Pancreatic Sarcoidosis: Diagnostic Challenge. Euroasian J Hepato
      Gastroenterol 2015;5(2):118-121.

PMID- 29201709
TI  - Clinical Presentation of Ulcerative Colitis in Pakistani Adults.
AB  - Objective: The aim of this study was to determine the clinical presentation and
      severity of ulcerative colitis (UC) in Pakistani adult patients. Materials and
      methods: An observational study. Data were obtained by reviewing the medical
      records of patients who visited a gastroenterology clinic between 2008 and 2012.
      Results: There were 54 patients diagnosed as UC. The male to female ratio was
      1:1. Mean age at diagnosis of UC was 38.7 +/- 11.8 years (median 36.5, range 18
      64). The predominant presenting symptoms were mucus diarrhea in 49 (90.7%), gross
      blood in stools in 42 (77.8%), abdominal pain or cramps in 40 (74.1%) and weight
      loss in 15 (27.7%). Left-sided colitis was present in 23 (42.6%), pancolitis in
      15 (27.8%), extensive colitis in 11 (20.4%), and proctitis in five (9.2%). The
      severity of UC as judged by the Mayo scoring system showed that 68.5% were
      suffering from moderate to severe disease while 31.5% had mild disease. The extra
      intestinal manifestation were found only in seven patients; arthritis in five
      patients and anterior uveitis in two patients. The arthritis was unilateral and
      the sites were knee joint in three patients and sacroiliac joint in two patients.
      Conclusion: Ulcerative colitis presents in our adult patients may present at any
      age with no gender preponderance. The disease severity is moderate to severe in
      the majority of patients and more than half of them have left-sided colitis or
      pancolitis at the time of presentation. Extraintestinal manifestations were not
      common. How to cite this article: Qureshi M, Abbas Z. Clinical Presentation of
      Ulcerative Colitis in Pakistani Adults. Euroasian J Hepato-Gastroenterol
      2015;5(2):127-130.

PMID- 29201708
TI  - A Case of Antimitochondrial Antibody Negative Primary Biliary Cirrhosis from
      Bangladesh and Review of Literature.
AB  - : Primary biliary cirrhosis (PBC) is very closely associated with the presence of
      antimitochondrial antibodies (AMA). Nevertheless, 5 to 10% of patients with
      typical features of primary biliary cirrhosis do not have detectable AMA. They
      are referred to as AMA negative PBC. We report a case of PBC who was AMA
      negative. The patient was a middle-aged woman seeking help of dermatologist for
      her complaint of itching. The diagnosis was confirmed by histopathology, whereas
      other possible causes of cirrhosis were excluded. How to cite this article: Begum
      R, Mahtab MA, Mamun AA, Saha BK, Hossain SMS, Saha DC, Akbar SMF, Kamal M, Rahman
      S. A Case of Antimitochondrial Antibody Negative Primary Biliary Cirrhosis from
      Bangladesh and Review of Literature. Euroasian J Hepato-Gastroenterol
      2015;5(2):122-126.

PMID- 29201710
TI  - Variant of Ascitic Fluid Bacterial Infections in Patients of Liver Cirrhosis.
AB  - Background and aims: Bacterial infections of ascitic fluid of cirrhotic patients
      are related to high morbidity and mortality. The aim of the study was to
      determine the variants of ascitic fluid bacterial infection in patients with
      advanced cirrhosis (Child Pugh Class C). Materials and methods: We analyzed 35
      consecutive cirrhotic patients of Child Pugh Class C with ascites attending the
      outpatient department (OPD) of Hepatology Department, Bangabandhu Sheikh Mujib
      Medical University, Dhaka, Bangladesh from January 2008 to December 2009.
      Clinical and laboratory parameters of these patients were recorded. Results:
      Among the total 35 patients, eight patients were symptomatic and 27 patients were
      asymptomatic. Out of eight symptomatic patients, two had ascitic fluid bacterial
      infection (25%), whereas six of 27 asymptomatic patients (22.2%) had ascitic
      fluid bacterial infection. Conclusion: Bacterial infection should always be
      considered in patients with ascites with liver cirrhosis irrespective of their
      symptoms. How to cite this article: Sarker JA, Alam MS, Khan M, Mahtab MA, Ashraf
      MS, Khondaker FA. Variant of Ascitic Fluid Bacterial Infections in Patients of
      Liver Cirrhosis. Euroasian J Hepato-Gastro-enterol 2015;5(2):131-133.

PMID- 29201711
TI  - Propylthiouracil-related Toxic Hepatitis: Impact of Silent Cases.
AB  - : Liver is the main organ which can metabolize many drugs or chemical agents.
      Toxic events developed by drugs are one of the most common causes of liver
      damage. Toxic hepatitis can be encountered in different clinical situations, such
      as acute hepatitis, fulminant hepatitis chronic hepatitis or cirrhosis. We aimed
      to report a case of asymptomatic toxic hepatitis in a patient taking
      propylthiouracil (PTU). A 38 years old female patient admitted to hospital
      complained of fatigue. She had no special medical history except Graves' disease.
      She had been taking PTU 300 mg/day for 1 month. She had no history of another
      medication, eating mushroom, alcohol consumption, traveling, family history of
      liver disease. Her physical examination was normal. Laboratory analysis revealed
      that alanine aminotransferase-543 U/L, aspartate aminotransferase-227 U/L, gamma
      glutamyl transferase-66 U/L and alkaline phosphatase-136 U/L. Serum levels of
      bilirubin and albumin, INR, complete blood count and thyroid function tests were
      all normal. She had normal liver function test (LFT) before using PTU.
      Propylthiouracil was discontinued and she was given methimazole. She was examined
      for the etiology of abnormal LFT, but no specific etiology could be recorded. She
      was thought to have toxic hepatitis related to PTU. In her follow-up LFT has
      turned to normal level (Table 1). How to cite this article: Eser M, Basyigit S,
      Eser M, Nazligul Y. Propylthiouracil-related Toxic Hepatitis: Impact of Silent
      Cases. Euroasian J Hepato-Gastroenterol 2015;5(2):134-135.

PMID- 29201712
TI  - New Cutoff Point for Platelet Count/Spleen Diameter Ratio to Predict Esophageal
      Varices in Patients with Hepatitis C Virus-related Hepatic Cirrhosis.
AB  - : The esophagogastroduodenoscopy (EGD) with all its hazards remains the gold
      standard screening tool for esophageal varices. Noninvasive tools have been
      proposed and studied to replace the EGD. Platelet count (PC)/spleen diameter (SD)
      ratio as a noninvasive tool for predicting the presence of esophageal varices was
      proposed and studied in many previous studies. How to cite this article: El
      Sherbiny W, Elegezy M, Shaltout SW. New Cutoff Point for Platelet Count/ Spleen
      Diameter Ratio to Predict Esophageal Varices in Patients with Hepatitis C Virus
      related Hepatic Cirrhosis. Euroasian J Hepato-Gastroenterol 2015;5(2):136-137.

PMID- 29201713
TI  - Editorial.

PMID- 29201714
TI  - Study on Liver Dysfunction in Type 2 Diabetic Patients in Bangladesh.
AB  - Aim: Diabetes mellitus (DM) represents one of the major lifestyle-related
      pathological conditions; the incidence and prevalence of DM have reached an
      epidemic level around the world. Diabetes mellitus is usually associated with
      obesity, coronary diseases, and cerebral pathologies. However, more insights are
      required to evaluate a temporal relation between DM and hepatic functions. This
      study assesses whether and to what extent liver functions are modified in DM
      patients. Materials and methods: A total of 100 patients with type 2 DM and 100
      normal healthy controls were enrolled in this study following proper scrutiny of
      inclusion and exclusion criteria. Different parameters of liver function tests
      were measured in patients in the two groups. Data were analyzed to assess the
      extent and magnitude of abnormal liver functions in DM. Results: The levels of
      bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      albumin, and prothrombin time were 0.737 +/- 0.311 mg/dL, 39.00 +/- 24.21 IU/L,
      26.42 +/- 10.40 IU/L, 4.10 +/- 0.513 g/dL, and 16.46 +/- 2.78 seconds in patients
      with DM and 0.506 +/- 0.183 mg/dL, 28.26 +/- 6.67 IU/L, 18.90 +/- 4.75 IU/L, 4.12
      +/- 0.277 g/dL, and 14.23 +/- 1.04 seconds in control subjects. Statistical
      analyses revealed that most of these parameters of liver function test were
      significantly different in DM patients compared to control subjects (p < 0.05).
      Serum alkaline phosphatase level was 89.61 +/- 25.59 mg/dL in type 2 DM patients
      and 96.83 +/- 16.34 mg/dL in control subjects (p > 0.05). The prevalence of
      abnormal values of serum bilirubin, ALT, AST, prothrombin time, and albumin were
      5.17, 31.03, 5.17, 5.17, 43.10, and 10.34% respectively in type 2 DM patients and
      0, 2, 0, 2, 3, and 0% respectively in control subjects, indicating high
      prevalence of DM patients with abnormal liver functions. Conclusion: Abnormal
      liver functions of different extents and magnitudes have been found in type 2 DM
      patients, and the impact of abnormal liver function should be considered during
      the management of DM patients and also to assess their long-term follow-up
      prognosis. How to cite this article: Rashid MHO, Haque MZ, Rahman MK, Khan MMR,
      Rahman ASMM, Al-Mahtab M, Rahman MS, Roy PK, Islam MN. Study on Liver Dysfunction
      in Type 2 Diabetic Patients in Bangladesh. Euroasian J Hepato-Gastroenterol
      2016;6(1):1-4.

PMID- 29201715
TI  - Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy
      Volunteers.
AB  - Aims: To see the prevalence of lactose intolerance (LI) and related symptoms
      following oral lactose challenge in healthy volunteers. Materials and methods:
      Symptoms of abdominal pain, nausea, borborygmi, flatulence, and diarrhea were
      noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after
      25 gm oral lactose load to healthy volunteers. Failure to rise blood glucose
      level >= 1.1 mmol/l at 30 minutes after lactose intake from fasting level was
      taken as lactose malabsorption (LM), i.e., LI. Results: A total of 166 volunteers
      (123 males, 43 females) with a mean age 34.78 +/- 11.45 years participated in
      this study. Lactose intolerance was found among 85.54% (n = 142, M = 104, F =
      38). The main symptoms of LI were diarrhea (n = 83, 58.4.0%), borborygmi (n = 81,
      57.04%), abdominal pain (n = 35, 24.65%), and flatulence (n = 27, 19.0%).
      Conclusion: Lactose intolerance among healthy adults may be common in Bangladesh.
      Diarrhea and borborygmi were mostly associated symptoms of LI. How to cite this
      article: Saha M, Parveen I, Shil BC, Saha SK, Banik RK, Majumder M, Salam MU,
      Nazmul Islam ASM. Lactose Intolerance and Symptom Pattern of Lactose Intolerance
      among Healthy Volunteers. Euroasian J Hepato-Gastroenterol 2016;6(1):5-7.

PMID- 29201716
TI  - The Evaluation of Serum Ascites Albumin Gradient and Portal Hypertensive changes
      in Cirrhotic Patients with Ascites.
AB  - Introduction: Ascites is a common complication of chronic liver diseases and is
      related to the extent of portal hypertension. This study evaluated whether the
      serum ascites albumin gradient (SAAG) (the difference between the albumin level
      of serum and of ascitic fluid) is endowed with clinical implications. Materials
      and methods: This is a prospective study involving 50 patients with cirrhosis of
      liver with ascites. The SAAG was measured in all patients and its relation with
      portal hypertensive changes was analyzed. Results: Based on SAAG values, the
      patients were divided into three groups: Group 1 - SAAG value 1.1 to 1.49 gm/dL
      (n = 15); group 2 - SAAG value 1.5 to 1.99 gm/dL (n = 9); and group 3 - SAAG
      value 2.0 gm/dL (n = 26). In group 1, 14 patients had esophageal varices (93.3%)
      and 13 had gastropathy (86.6%). In group 2, all 9 patients had esophageal varices
      (100%), 7 (77.7%) had gastropathy, and 1 (11.1%) had gastric varices. In group 3,
      all 26 patients had esophageal varices (100%), 24 patients (92.3%) had
      gastropathy, and 1 patients (3.8%) had gastric varices. Conclusion: Serum ascites
      albumin gradient value is weakly related to the extent of portal hypertension in
      patients with liver cirrhosis and its implication seems to be limited in clinics.
      How to cite this article: Shahed FHM, Al-Mahtab M, Rahman S. The Evaluation of
      Serum Ascites Albumin Gradient and Portal Hypertensive changes in Cirrhotic
      Patients with Ascites. Euroasian J Hepato-Gastroenterol 2016;6(1):8-9.

PMID- 29201717
TI  - Plasma Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of
      Liver.
AB  - Introduction: Cirrhosis of the liver is a common complication of chronic liver
      disease and is associated with portal hypertension and esophageal varices. In
      this study, we checked the implication of prothrombin time, if any, in the
      genesis of esophageal varices. Materials and methods: Sixty patients with
      cirrhosis of the liver were randomly assigned into two groups: Group I - 30
      cirrhotic patients with esophageal varices, and group II - 30 cirrhotic patients
      without esophageal varices. The prothrombin time was checked for both groups.
      Results: A positive correlation was found between the prolonged plasma
      prothrombin time (> 4 seconds) and esophageal varices with a sensitivity of
      56.67% and specificity of 73.33%. The Child-Pugh score showed a correlation;
      however, the size of varices did not exhibit any such relation. Conclusion:
      Prothrombin time may be cautiously used to assess portal hypertension in a field
      level and rural setting where endoscopy is not available or feasible. How to cite
      this article: Islam MN, Khan M, Ahmad N, Al-Mahtab M, Karim MF. Plasma
      Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of Liver.
      Euroasian J Hepato-Gastroenterol 2016;6(1):10-12.

PMID- 29201718
TI  - Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver
      Disease.
AB  - Background and aims: Insulin resistance and cytokine production are key
      mechanisms leading to fatty change in the liver and may produce nonalcoholic
      steatohepatitis (NASH). Oxidative stress may also contribute to clinical
      progression from simple fatty liver (FL) to NASH. A therapy for insulin
      resistance and antioxidant has been applied to treat NASH, yet these treatments
      are not fully established. In the present study, we have evaluated whether an
      antioxidant agent, glutathione, prevents the development of NASH from FL.
      Materials and methods: Five patients with FL and 10 with NASH were enrolled in
      the study. Three hundred milligrams per day of glutathione was given orally to
      patients with nonalcoholic fatty liver disease (NAFLD) every day, and an
      oxidative stress marker and biochemical tests were analyzed before treatment and
      1 and 3 months after starting the treatment. We measured serum levels of 8
      hydroxy-2-deoxyguanosine (8-OHdG) and gamma-glutamyltranspeptidase (GGT).
      Immunohistochemistry for glutathione was performed on formalin fixed liver
      specimens obtained from liver biopsies. Results: Before treatment, the NASH group
      had higher serum 8-OHdG and lower serum glutathione levels than the FL group.
      Immunohistochemistry revealed that a strong expression of glutathione was
      observed in zone 3 in both NASH and FL before treatment. Serum levels of alanine
      transaminase and 8-OHdG were significantly decreased after treatment in the NASH
      group. Gamma-glutamyltranspeptidase was decreased after treatment, although the
      decrease was statistically not significant. Discussion: The present pilot study
      demonstrated that antioxidant therapy with glutathione may reduce the
      pathological oxidative stress in the liver in NASH, preventing the progression
      from NAFLD to NASH. How to cite this article: Irie M, Sohda T, Anan A, Fukunaga
      A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S.
      Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver
      Disease. Euroasian J Hepato-Gastroenterol 2016;6(1):13-18.

PMID- 29201719
TI  - High Functional Stability of a Low-cost HBV DNA qPCR Primer Pair and Plasmid
      Standard.
AB  - Aim: We studied the functional stability of a primer pair and the standard curve
      based on a plasmid carrying full-length HBV genome, from a novel low-cost real
      time quantitative polymerase chain reaction (qPCR) assay. The assay was developed
      at the Center for Genetic Engineering and Biotechnology (CIGB) in Havana, to
      quantify the serum hepatitis B virus (HBV) DNA from chronic HBV-infected (CHB)
      patients. Materials and methods: In-house generated oligonucleotides and plasmids
      were incubated at 37 degrees C during 1 month and compared with the same
      materials incubated at -20, 4, and 25 degrees C during the same time in qPCR
      experiments. Results: This work shows that the oligonucleotide pair and the
      plasmid for the quantitative standard curve are functionally stable in severe
      temperature conditions during 1 month. Polymerase chain reaction amplification
      with both materials after its incubation 30 days at 37 degrees C produced similar
      cycle threshold (CT) values and similar degree of sample quantifications compared
      with the same materials preserved using the conventional storage conditions at 
      20 degrees C. Conclusion: These results are indicative of the robustness of this
      low-cost qPCR system for HBV DNA quantification. These results also support that
      this qPCR assay can be used as a low-cost technology in clinical studies to
      monitor the viral load changes of serum HBV DNA of CHB patients, which could be
      used by poor people of third world countries, where there are frequent blackouts
      and temperature changes that can hinder the primer and plasmid stability. How to
      cite this article: Aguiar J, Garcia G, Leon Y, Canales E, Silva JA, Gell O,
      Estrada R, Moran I, Muzio V, Guillen G, Penton E, Aguilar JC. High Functional
      Stability of a Low-cost HBV DNA qPCR Primer Pair and Plasmid Standard. Euroasian
      J Hepato-Gastroenterol 2016;6(1):19-24.

PMID- 29201720
TI  - Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice
      Immunized with a Novel Therapeutic Formulation.
AB  - : The development of therapeutic vaccines against chronic hepatitis B requires
      the capacity of the formulation to subvert a tolerated immune response as well as
      the evaluation of histopathological damage resulting from the treatment. In the
      present study, the dynamicity of induced immune response to hepatitis B surface
      antigen (HBsAg) was evaluated in transgenic mice that constitutively express the
      HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate
      containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus
      (HBV), the effect of vaccination on clearance of circulating HBsAg and the
      potential histological alterations were examined. Transgenic (tg) and non
      transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC)
      routes simultaneously. A control group received phosphate-buffered saline (PBS)
      by IN route and aluminum by SC route. Positive responses, at both humoral and
      cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such
      responses were delayed and of lower intensity in tg mice, compared to vaccinated
      Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern.
      Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma
      interferon ELISPOT assay, histopathological alterations were not detected in any
      organ, including the liver and kidneys. Our study demonstrated, that it is
      possible to subvert the immune tolerance against HBsAg in tg mice, opening a
      window for new studies to optimize the schedule, dose, and formulation to improve
      the immune response to the therapeutic vaccine candidate. These results can be
      considered a safety proof to support clinical developments for the formulation
      under study. How to cite this article: Freyre FM, Blanco A, Trujillo H, Hernandez
      D, Garcia D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune
      Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a
      Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30.

PMID- 29201721
TI  - Impact of Periampullary Diverticula on Bile Duct Stones and Ampullary Carcinoma.
AB  - Introduction: Periampullary diverticula (PD) is caused by extraluminal pouching
      of duodenal mucosa. Using a very common endoscopic procedure to diagnose or treat
      gastrointestinal disorders, we encountered duodenal diverticulum. Materials and
      methods: This is a retrospective, single-center study. Three thousand and sixteen
      patients on whom endoscopic retrograde cholangiopancreatography (ERCP) was
      performed at Ankara University Medical School, Department of Gastroenterology,
      from June 2009 to June 2014 were included to the study. Results: Hundred and
      thirty patients (males 65, females 65) among the 3,016 had PD. Two hundred and
      sixty patients without diverticulum were randomly chosen from the 3,016 patients,
      as a control group [121 (47%) females, 139 (53%) males]. There was no statistical
      difference between the two groups. The mean age of the patients with PD was 69.9
      years, while the mean age was 62.3 years for patients without PD (p < 0.001).
      Incidence for PD was 4.6%. The papilla of Vater was located in the inter
      diverticular area (Type 1) in 9 patients (8.3%), at the edge of the diverticulum
      (Type 2) in 31 patients (28.4%), and at a distance of 2 to 3 cm from the papilla
      (Type 3) in 69 patients (63.3%). Discussion: Although numerically more common
      bile duct stones occurred in patients with PD compared to those without PD, there
      was no statistical difference between the two groups. The rate of pancreato
      biliary carcinomas was higher in patients without diverticulum. Cannulation was
      successful in both groups at the rate of 97.6 and 92% respectively, but
      cannulation failed more often in patients without PD. Duodenal perforation
      occurred in one patient with PD. Bleeding after sphincterotomy occurred in two
      patients without PD. How to cite this article: Ormeci N, Deda X, Kalkan C, Tuzun
      AE, Karakaya F, Dokmeci A, Bahar DK, Ozkan H, Idilman R, Cinar K. Impact of
      Periampullary Diverticula on Bile Duct Stones and Ampullary Carcinoma. Euroasian
      J Hepato-Gastroenterol 2016;6(1):31-34.

PMID- 29201723
TI  - Past, Present, and Future of Viral Hepatitis in Bangladesh.
AB  - : Viral hepatitis poses huge burden to the health care delivery system as well as
      to the economy of Bangladesh. Hepatitis E virus is the leading cause of acute
      hepatitis in this country, however with the improvement of economic status and
      sanitation this seems to be on the decline. Hepatitis B virus remains the leading
      cause in all forms of chronic liver diseases in this country. This virus has been
      extensively studied in Bangladesh, including from epidemiology to pathogenosis.
      Clinical trials with innovative therapy conducted in Bangladesh have shown
      promise. Hepatitis C virus follows hepatitis B virus as the second commonest
      cause of chronic liver diseases here. However patients in Bangladesh have started
      benefitting from the local generic versions of the newly introduced direct acting
      anti-virals. How to cite this article: Al-Mahtab M. Past, Present, and Future of
      Viral Hepatitis in Bangladesh. Euroasian J Hepato-Gastroenterol 2016;6(1):43-44.

PMID- 29201722
TI  - Tackling HCV-3 in Asia: Breakthroughs for Efficient and Cost-effective Treatment
      Strategies.
AB  - : Hepatitis C virus (HCV) is known to cause chronic hepatitis C, and its sequelae
      of cirrhosis and hepatocellular carcinoma. Hepatitis C genotype 3 (HCV-3) in
      particular is notorious for causing accelerated liver fibrosis, cardiovascular,
      and metabolic effects, thus increasing morbidity and mortality. It is the
      commonest variant in Asian countries like India and Pakistan. It is also one of
      the hardest-to-treat genotypes, especially among treatment-experienced and
      cirrhotic patients. Due to limited health care affordability and accessibility in
      these areas, many patients remain untreated. Until recently, the established
      therapy for HCV had been a combination of pegylated interferon + ribavirin.
      However, it was only effective in about half of patients and had severe adverse
      effects; hence a more efficacious option needed to be found. Recent advances have
      led to the development of sofosbuvir, an NS5B inhibitor that is fast becoming the
      standard of care, in combination with other novel drugs. It was initially
      marketed at $1,000 per pill, a cost that was too high for most. Thus, it has not
      been utilized as a global therapy as yet. Formulation of effective interferon
      free regimens is a huge milestone, and awareness needs to be raised regarding
      these new highly effective options in both the physician and the patient
      population. This article discusses the newest drugs and combinations that have
      been developed in the fight against HCV-3, as a treatment outline for HCV-3
      dominant areas. It also highlights recent breakthroughs in cost reductions of
      these drugs and the effort to make them globally accessible. How to cite this
      article: Saeed N, Gurakar A. Tackling HCV-3 in Asia: Breakthroughs for Efficient
      and Cost-effective Treatment Strategies. Euroasian J Hepato-Gastroenterol
      2016;6(1):35-42.

PMID- 29201724
TI  - Viral Hepatitis in Cambodia: Past, Present, and Future.
AB  - : The prevalence of viral hepatitis represents Cambodia as 1 of the highest
      endemic countries in the world. But the prevalence of viral hepatitis B among 5
      year-olds is on a decreasing trend due to the effect of nationwide vaccination
      against hepatitis B. There are key interventions to address viral hepatitis by
      the Cambodian Ministry of Health. There are so far no comprehensive national
      guidelines for the prevention, care, and treatment of viral hepatitis. In 2014,
      the coverage of hepatitis B vaccine at birth and HepB3 vaccine was very high, at
      87 and 97% respectively. Other interventions include the screening of viral
      hepatitis B and C among blood donors; the enhancement of infection prevention and
      control at health facilities; the program for People Who Use Drugs (PWUDs) and
      People Who Inject Drugs (PWIDs); control and prevention of HIV/AIDS and sexually
      transmitted diseases (STDs); and improved sanitation, clean water, and food
      safety. The diagnosis of viral hepatitis B and C could be made only at the
      national and provincial referral hospitals and there are no specific antiviral
      therapies for people who are infected with hepatitis B and C. How to cite this
      article: Sreng B, Sophal C, Srun S, Samnang C, Huot E. Viral Hepatitis in
      Cambodia: Past, Present, and Future. Euroasian J Hepato-Gastroenterol
      2016;6(1):45-48.

PMID- 29201725
TI  - Past, Present, and Future of Viral Hepatitis C in Japan.
AB  - : Of all the industrialized countries of the world, Japan has the highest rate of
      hepatitis C. It also has 1 of the oldest and most varied histories of hepatitis C
      in the world among the industrialized modern nations. Hepatitis C and its
      complications are the leading cause of liver cancer in Japan. Japan has the
      highest rate of liver cancer among the industrialized countries. From 2004 to
      2014, PegIFN/RBV treatment was the mainstream of hepatitis C treatment. In 2014,
      the first interferon-free therapy was approved in Japan. Subsequently, other
      interferon-free therapies have been approved. Hepatitis C virus disinfection in
      hepatitis C patients in Japan has become possible with a probability of 96% or
      more. How to cite this article: Yatsuhashi H. Past, Present, and Future of Viral
      Hepatitis C in Japan. Euroasian J Hepato-Gastroenterol 2016;6(1):49-51.

PMID- 29201726
TI  - Hepatitis in Malaysia: Past, Present, and Future.
AB  - : Malaysia is multiethnic, with a population of 31,127,247 comprising a mixture
      of Malays (50.1%), Chinese (22.6%), Indians (6.7%), Aborigines (11.8%), others
      (0.7%), and noncitizens (8.2%). Like other countries in the region, viral
      hepatitis is an important public health problem in Malaysia. The 3 most common
      causes for hepatitis in Malaysia are hepatitis A, B, and C. Hepatitis A has been
      a reportable disease in Malaysia since 1988. Due to the introduction of
      government control programs, the national incidence rate has dropped steadily. It
      is now estimated that 50% of Malaysians less than 30 years of age do not have
      antibodies to hepatitis A and are therefore susceptible to the disease, which can
      be prevented by reinforcing the hygiene status of the general population.
      Malaysia is a country of medium seroprevalence for the hepatitis B virus (HBV)
      surface antigen (HBsAg) in the general population (1.5-9.8%). The major route of
      transmission is from infected mother to fetus. There are an estimated 1 million
      people chronically infected with hepatitis B in Malaysia. Approximately 75% of
      all viral hepatitis cases are due to hepatitis B infection, with a male-to-female
      ratio of 2:1. Chronic hepatitis B (CHB) accounts for more than 80% of the
      hepatocellular carcinoma (HCC) cases seen in Malaysia and HCC is the 3rd most
      common malignant neoplasm and among the 10 leading causes of death. Most common
      genotypes are B and C. Incidence rates among Chinese, Malays, and Indians are 36,
      26, and 15% respectively. The hepatitis B vaccination program for children was
      introduced in 1989, which successfully managed to reduce the seroprevalence of
      infection among Malaysians to 0.01% (graph 4, 2014). But the disease burden will
      still remain high for some time as the infected people are getting older and
      living longer. Hepatitis C virus (HCV) infection is a growing problem in
      Malaysia. An estimated 453,700 people were living with HCV infection in Malaysia
      in 2009 (2.5% of the population aged 15-64 years), of whom 59% acquired their
      infection through injection and the most common genotypes found are genotype 3
      and 1. The HCV-related disease burden is already high and is forecast to rise
      steeply over the coming decades under current levels of antiviral treatment.
      Increased governmental resources to improve HCV screening and treatment rates and
      to reduce transmission are essential to address the high projected HCV disease
      burden in Malaysia. How to cite this article: Raihan R. Hepatitis in Malaysia:
      Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):52-55.

PMID- 29201727
TI  - Viral Hepatitis in Mongolia: Past, Present, and Future.
AB  - : Viral hepatitis is one of the major health concerns worldwide, particularly in
      Asian countries. Mongolia, which is located in northern Asia, between Russia and
      China, is confronting various infectious diseases, such as viral hepatitis and
      tuberculosis. As for healthy individuals in Mongolia, the reported prevalence of
      hepatitis B surface antigen (HBsAg) was 9 or 10% and the reported prevalence of
      anti-hepatitis C virus ranged from 11 to 25%. We reported a markedly high
      prevalence of hepatitis D virus RNA (83%) among apparently healthy individuals
      with HBsAg in Ulaanbaatar. Also due to lack of proper mechanisms to handle
      sewerage, disinfection, and lack of clean water supply across the country,
      hepatitis A is endemic in Mongolia. Moreover, Mongolia ranked in the high
      prevalence zone for hepatitis B, D, and C. How to cite this article: Tsatsralt-Od
      B. Viral Hepatitis in Mongolia: Past, Present, and Future. Euroasian J Hepato
      Gastroenterol 2016;6(1):56-58.

PMID- 29201728
TI  - Viral Hepatitis in Nepal: Past, Present, and Future.
AB  - : Over the last four decades, the diagnosis and therapy of viral hepatitis has
      evolved substantially all over the world. Although Nepal is a developing nation,
      it has been keeping pace with these developments in terms of the implementation
      of diagnostic and therapeutic strategies. However, because of a lack of
      infrastructure and logistics, Nepal still depends on its neighboring countries
      for molecular diagnostics in viral hepatitis B and C. Though most of the recent
      antivirals for hepatitis B and directly acting antivirals for hepatitis C are
      available at a highly subsidized cost, affordability still remains an issue. A
      lack of comprehensive national program for hepatitis B and C has been a major
      barrier for access to health care in patients with chronic viral hepatitis.
      Similarly, hepatitis E still remains an important public health issue with major
      epidemics at periodic intervals. Recent developments in understanding hepatitis E
      virus have unveiled important aspects of the virus, particularly with regard to
      why these epidemics occur. In this manuscript we try to elaborate the evolution
      in understanding, diagnosing, and treating viral hepatitis in Nepal. How to cite
      this article: Shrestha A. Viral Hepatitis in Nepal: Past, Present, and Future.
      Euroasian J Hepato-Gastroenterol 2016;6(1):59-61.

PMID- 29201729
TI  - Viral Hepatitis in Korea: Past, Present, and Future.
AB  - : Korea has been one of the endemic areas of hepatitis B virus (HBV; exclusively
      genotype C) infection since ancient times. The epidemiology of HBV in Korea is
      easily expected to have changed over the last two decades owing to the high
      coverage rate of universal HBV vaccination. The main mode of hepatitis C virus
      (HCV) infection may have been effectively blocked since 1992 when compulsory
      blood screening for anti-HCV was implemented, and consequently, the prevalence of
      anti-HCV is also expected to have markedly decreased during the last two decades.
      This review will briefly describe what really happened during the last couple of
      decades in the epidemiology of HBV and HCV and in the incidence and mortality
      rates of liver cirrhosis (hepatic failure) and hepatocellular carcinoma in Korea.
      How to cite this article: Lee H-S. Viral Hepatitis in Korea: Past, Present, and
      Future. Euroasian J Hepato-Gastroenterol 2016;6(1):62-64.

PMID- 29201730
TI  - Viral Hepatitis in Indonesia: Past, Present, and Future.
AB  - : Since Indonesia is a huge archipelago country, the prevalence of hepatitis
      virus infection highly varies among islands. In average the prevalence of
      clinical hepatitis in Indonesia was 0.6% in the year 2007. Of 82 clinical acute
      hepatitis patients treated in hospitals in several cities, acute hepatitis A
      accounted for 28.0%, acute hepatitis B 13.4%, and acute hepatitis C 1.2%; 35.4%
      patients were infected by unknown etiology. In 1980s, the prevalence of anti-HAV
      in the age group 10- to 14-years was almost 100% in smaller towns and 45 to 60%
      in big cities. About 30 years later, anti-HAV prevalence decreased to around 13%
      in the same smaller town. Outbreaks of hepatitis A were reported between 2006 and
      2009 in several cities in Java island. The prevalence of HBsAg in the islands
      other than Java island (8.5%) was significantly higher than in Java island
      (4.9%). In 1,409 viremic subjects, 4 genotypes of HBV were found, i.e., genotype
      B (60%), followed by genotype C (33%), genotype D (7%), and genotype A (0.3%). In
      contrast, the prevalence of hepatitis C was much higher in Java island compared
      to other islands. In blood donors in Java island, the prevalence of anti-HCV and
      HCV RNA were 1.5 and 1.1% respectively, while in other islands, the prevalence
      were only 0.7 and 0.2% respectively. Hepatitis D was very rare in Indonesia, and
      so was hepatitis E. Outbreaks of hepatitis E were reported between 1989 and 1993
      in West Kalimantan. Afterward, the incidence of hepatitis E was reported
      sporadically. How to cite this article: Mulyanto. Viral Hepatitis in Indonesia:
      Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):65-69.

PMID- 29201732
TI  - A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B
      Virus Earlier.
AB  - : Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver.
      Hepatitis B virus infection is one of the most important etilogical factors of
      HCC. In this case report, a patient with HCC previously infected and having
      ongoing immunity against hepatitis B virus will be discussed. How to cite this
      article: Ates I, Kaplan M, Demirci S, Altiparmak E. A Hepatocellular Carcinoma
      Case in a Patient Who had Immunity to Hepatitis B Virus Earlier. Euroasian J
      Hepato-Gastroenterol 2016;6(1):82-83.

PMID- 29201731
TI  - Viral Hepatitis in Pakistan: Past, Present, and Future.
AB  - : Viral hepatitis is a major cause of morbidity and mortality worldwide and a
      rising cause for concern in Asian countries. Weather it is blood borne or
      water/food borne hepatotropic virus, increasing burden is alarming for Asian
      countries. In this review we have evaluated the existing data to estimate the
      burden of viral hepatitis in populations of all age groups nationwide, along with
      an assessment of the risk factors and preventive and management strategies
      currently employed in Pakistan. The aim of our work is to consolidate and
      supplement the present knowledge regarding viral hepatitis in light of past and
      present trends and to provide future direction to the existing health policies.
      How to cite this article: Butt AS, Sharif F. Viral Hepatitis in Pakistan: Past,
      Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):70-81.

PMID- 29201733
TI  - Brunneroma: A Rare Cause of Duodeno-duodenal Intussusception.
AB  - : Brunner gland hamartoma (brunneroma) is a rare benign tumor of the duodenum. It
      is usually asymptomatic and detected incidentally by endoscopy or other imaging
      modality. The definitive diagnosis is based on histopathological findings. These
      may mimic tumors of other natures, such as gastrointestinal stromal tumors
      (GIST), carcinoids, lipomas, and leiomyomas. Here, we present a case of duodenal
      polyp presenting with abdominal pain and obstructive symptoms that caused
      duodenal intussusception. It was surgically removed and found to be a brunneroma
      on histopathology. How to cite this article: Patankar AM, Wadhwa AM, Bajaj A,
      Ingule A, Wagle P. Brunneroma: A Rare Cause of Duodeno-duodenal Intussusception.
      Euroasian J Hepato-Gastroenterol 2016;6(1):84-88.

PMID- 29201734
TI  - A Case of Organic Acidemia: Are Physicians Aware Enough?
AB  - : Diversity of clinical presentation of inborn errors of metabolism (IEM) gives a
      diagnostic challenge to the practicing physicians. In recent years there have
      been dramatic advances in the diagnosis and treatment of these fatal diseases,
      which shows improved prognosis of many of these conditions. The need for
      screening for IEM arises out of the fact that most cases take to irreversible
      effects as time progresses. Here, the main challenge is to recognize the early
      signs and symptoms that are also common to sick infants with other diseases. We
      describe a 32-day-old female infant who was finally diagnosed as a case of IEM
      (organic acidemia).The baby had a history of multiple neonatal intensive care
      unit admission. She died during her last hospital admission. The purpose of our
      case presentation is to provide clues to the true nature of the disease and to
      make physicians aware about the possibility of IEM. How to cite this article:
      Mosleh T, Dey SK, Mannan MA. A Case of Organic Acidemia: Are Physicians Aware
      Enough? Euroasian J Hepato-Gastroenterol 2016;6(1):89-90.

PMID- 29201735
TI  - Interstitial Pneumonitis Related to Pegylated Interferon Alfa-2a Treatment in a
      Patient with Chronic Hepatitis C.
AB  - Alkan E, Akin M, Adanir H, Tuna Y. Interstitial Pneumonitis Related to Pegylated
      Interferon Alfa-2a Treatment in a Patient with Chronic Hepatitis C. Euroasian J
      Hepato-Gastroenterol 2016;6(1):91-92.

PMID- 29201736
TI  - Editorial.

PMID- 29201737
TI  - Helicobacter pylori Infection among Patients with Dyspepsia and Intrafamilial
      Transmission.
AB  - Introduction: Recurrence is an important problem after Helicobacter pylori
      infection, and intrafamilial transmission has an important role in recurrence. In
      this study, we aimed to investigate the significance of intrafamilial
      transmission for recurrence development after treatment as well as its usefulness
      in prevention. Materials and methods: Of the 109 patients who had dyspepsia and
      underwent endoscopy, 74 patients had H. pylori infection and were enrolled in
      this study. Infected family members were also detected. Patients were randomly
      divided into groups I and II, with each group containing 37 individuals. In group
      I, patients and their infected family members were treated together at the same
      time. In group II, only the patients were treated. Treatment success was
      evaluated at the 1st month and evaluation for recurrence was carried out at the
      6th month. Results: Helicobacter pylori infection was detected in 67.8% of the
      patients with dyspepsia. Two patients in each group did not show up at the 1st
      month control. Eradication was achieved in 63 of the 70 patients (90.0%) who
      completed their treatment. After 6 months, patients with successful treatment had
      no recurrence in any of the 32 patients in group I. There were recurrence in 3 of
      the 31 patients (9.7%) in group II; however, there was no statistically
      significant difference between the groups (p = 0.113). Conclusion: Our study
      showed that eradication treatment in patients and family members with H. pylori
      infection resulted in a decrease in the number of recurrences even though it was
      not statistically significant. How to cite this article: Yalcin M, Yalcin A,
      Bengi G, Nak SG. Helicobacter pylori Infection among Patients with Dyspepsia and
      Intrafamilial Transmission. Euroasian J Hepato-Gastroenterol 2016;6(2):93-96.

PMID- 29201738
TI  - Histopathological Assessment of Dyspepsia in the Absence of Endoscopic Mucosal
      Lesions.
AB  - Introduction: Dyspepsia is a common symptom with an extensive differential
      diagnosis. Endoscopy alone may miss serious mucosal lesions in about 15 to 30% of
      cases. The aim was to determine histopathological features of gastric and
      duodenal mucosal biopsies in patients with dyspepsia and normal looking upper
      gastrointestinal (GI) endoscopy. Materials and methods: One hundred and five
      adult patients presenting with dyspepsia with no endoscopic mucosal lesions in
      the upper GI tract were included. Gastric biopsy specimens according to Sydney
      Houston system for grading gastritis and biopsy from duodenum were taken. The
      histopathological features were graded according to the Sydney-Houston system
      classification for grading gastritis. Results: The histological lesions were
      found in 65.7% (69 out of 105 endoscopy free dyspeptic patients). Chronic
      inflammation was the commonest finding. Neutrophilic activity, glandular atrophy,
      and mild degree of intestinal metaplasia were present in 27, 45, and 6 patients
      (22.8, 42.8, and 5.7% respectively). Helicobacter pylori was present in 54
      patients with histopathological lesions and in 6 patients without
      histopathological lesions, and the difference was significant (p = 0.045).
      Conclusion: The endoscopic diagnosis of dyspepsia correlated poorly with
      histopathological findings. The histopathological examination allowed detection
      and grading of gastric pathology in dyspepsia with normal endoscopy and the
      commonest finding was the moderate chronic gastritis. How to cite this article:
      Dawod HM, Emara MW. Histopathological Assessment of Dyspepsia in the Absence of
      Endoscopic Mucosal Lesions. Euroasian J Hepato-Gastroenterol 2016;6(2):97-102.

PMID- 29201739
TI  - Is There any Association Between Celiac Disease and Helicobacter pylori?
AB  - Objective: It was aimed to determine if there was a correlation between celiac
      disease (CD) and Helicobacter pylori (H. pylori) by comparing the prevalence of
      H. pylori in patients with and without CD. Materials and methods: The patients
      who were diagnosed with CD and tested for H. pylori and the patients who
      presented for gastroscopy and tested for H. pylori were evaluated retrospectively
      and the prevalence of H. pylori was compared. Results: Fifteen (48%) of 31
      patients who were diagnosed with CD and tested for H. pylori were males and had a
      mean age of 33.1 +/- 12.7 years (17-72). In the CD group, H. pylori was positive
      in 15 patients (48%), and 592 antrum biopsy that was performed were included as
      the control group. Of these patients, 299 (50.5%) were males and had a mean age
      of 44.4 +/- 17.05 years (16-96). Helicobacter pylori were positive in 316
      patients (53.4%). Helicobacter pylori prevalence was similar in the groups with
      and without CD (p > 0.5). Conclusion: Although the prevalence of H. pylori was
      lower in celiac patients compared to the control group, the difference was not
      statistically significant. Although no findings suggesting a correlation between
      CD and H. pylori was found, further studies should be conducted. How to cite this
      article: Uyanikoglu A, Dursun H, Yenice N. Is There any Association Between
      Celiac Disease and Helicobacter pylori? Euroasian J Hepato-Gastroenterol
      2016;6(2):103-105.

PMID- 29201740
TI  - Type 1 Gastric Carcinoid in the Indian Population and Its Association with
      Multifocal Gastric Atrophy.
AB  - Aim: Recent studies have shown an increase in the incidence of gastric
      neuroendocrine tumors (NETs) (carcinoids). This may be attributable to the
      frequent employment of endoscopy in clinical practice and the increasing use of
      proton pump inhibitors. From the literature that is available, it is interesting
      to note that the profile of patients with gastric carcinoids is different in the
      Asian population when compared to the western societies. As limited data is
      available from India, we evaluated retrospectively the clinical profile and
      pathology of gastric carcinoids presenting to our hospital. Materials and
      methods: A total of 31 patients with gastric carcinoids who presented to our
      institution from 2006 till 2013 were included in this study. The clinical data
      were obtained from the case files and the histopathology slides were reviewed.
      Results: Gastric carcinoids constituted about 32% of all gastrointestinal (GI)
      NETs and were second only to duodenal carcinoids in frequency. Men were more
      commonly affected (74%) and the majority were of type 1 (90%). Multifocal gastric
      atrophy with intestinal metaplasia was additional features seen in the majority
      of cases with type 1 carcinoids. Conclusion: This study, one of the largest
      series reported from India, shows that the frequency and profile of gastric
      carcinoids is different in this population when compared to the west. It also
      raises the possibility that Helicobacter pylori induced multifocal gastric
      atrophy might be a triggering factor for the most common type 1 gastric carcinoid
      rather than autoimmune gastritis. Clinical significance: Eradication of H.pylori
      may be a potential preventive strategy for the occurrence of gastric carcinoids.
      How to cite this article: Ananthamurthy A, Correa M, Patil M. Type 1 Gastric
      Carcinoid in the Indian Population and Its Association with Multifocal Gastric
      Atrophy. Euroasian J Hepato-Gastroenterol 2016;6(2):106-110.

PMID- 29201741
TI  - Profile of Acute Liver Failure from North-east India and Its Differences from
      other Parts of the Country.
AB  - Background: Acute liver failure (ALF) is a critical illness with a large number
      of viral and nonviral causes. Clinical course and etiologies in the Asian
      countries are different from those reported from the Western world and mortality
      is high. There may even be intracountry variations in large countries like India,
      which have differing culture, ethnicity, and environment. Data from North-east
      part of India is lacking. Materials and methods: Acute liver failure cases (>14
      years of age) seen over a period of 8 years (n = 255) were studied at a
      Government Medical College in Assam for their etiological and other demographic
      profile. Viral serology was carried out and revalidated at a laboratory in New
      Delhi. Results: Majority of cases were <30 years of age. Commonest etiology was
      nonviral (non-ABCE). Amongst viral causes, hepatitis A and E were common, while
      hepatitis B virus (HBV) was rare. Unknown herbal medication use was very frequent
      in our cases with a significantly higher mortality. Mortality was highest in
      cases in 3rd decade of life. Statistically, international normalized ratio (INR)
      was the strongest predictor of death. Conclusion: Unlike the rest of India,
      hepatitis virus is not the major cause of ALF in our part; hepatitis A being
      commoner than hepatitis E, and B is rare. Unknown herbal medications are major
      cause of mortality and is important medicosocial issue. Our study highlights the
      differences in the profile of ALF from other Indian and western studies, possibly
      due to sociocultural factors prevalent in this part. How to cite this article:
      Das AK, Begum T, Kar P, Dutta A. Profile of Acute Liver Failure from North-east
      India and Its Differences from other Parts of the Country. Euroasian J Hepato
      Gastroenterol 2016;6(2):111-115.

PMID- 29201742
TI  - Fecal Calprotectin for predicting Relapse and Activity in Patients with Crohn's
      Disease: A Meta-analysis.
AB  - Aims: We aimed to perform a meta-analysis of the predictive capacity of fecal
      calprotectin (FC) in activity and relapse of Crohn's disease (CD). Materials and
      methods: MEDLINE, EMBASE, and the Cochrane Library databases were searched
      systematically. Pooled sensitivity, specificity, and other diagnostic indices
      were evaluated. Results: A total of 1,252 CD patients from 18 different studies
      were analyzed. The pooled sensitivity and specificity of FC at a cutoff value of
      50 MUg/g to predict activity of CD were 0.91 [95% confidence interval (CI): 0.87
      0.95] and 0.47 (95% CI: 0.35-0.59) respectively. The pooled sensitivity and
      specificity of FC at a cutoff value of larger than 150 MUg/g to monitor relapse
      of CD was 0.75 (95% CI: 0.67-0.82) and 0.71 (95% CI: 0.66-0.76) respectively. The
      area under the summary receiver operating characteristic (SROC) curve of FC for
      detecting CD activity was 0.78 (50 MUg/g), 0.88 (100 MUg/g), 0.85 (>150 MUg/g),
      and the diagnostic odds ratio (DOR) was 10.21 (50 MUg/g), 10.20 (100 MUg/g),
      11.68 (>150 MUg/g) respectively. Conclusion: As a simple and noninvasive marker,
      FC is useful to predict the activity and relapse in CD patients, and the capacity
      of FC to predict CD activity was superior to its application in monitoring
      relapse of CD. How to cite this article: Zhuge Y, Huang Q-P, Li Q, Wang J-S.
      Fecal Calprotectin for predicting Relapse and Activity in Patients with Crohn's
      Disease: A Meta-analysis. Euroasian J Hepato-Gastroenterol 2016;6(2):116-124.

PMID- 29201743
TI  - Liver Echinococcosis complicated with Lesions of Bile Ducts in Azerbaijan.
AB  - : A total of 302 patients with liver echinococcosis (LE) complicated by lesions
      of bile duct during 1988 to 2015 were analyzed. The patients were divided into
      two groups. In the first group, 227 patients were included with lesions of
      segmental bile ducts in the form of cystobiliary and bilio-bronchial fistulas. In
      the second group, 75 patients with lesions of hepatic bile were enrolled.
      Diagnosis of LE and its complications was made by ultrasonography and computed
      tomography (CT). Surgical treatment included echinococcectomy with complete
      liquidation of a residual cavity (35.1%), echinococcectomy with suturing (46.0%),
      external drainage of a residual cavity (7.3%), pericystectomy (8.6%), and
      resection of a liver (3.0%). Postoperative complications related to operative
      intervention developed in 29 patients. Lethal outcomes took place in 6 cases
      (2.0%). The analysis has shown that the form of bile duct lesions, methods of
      surgical operation for liquidation of hydatid cysts, and its biliary
      complications had influenced the treatment outcome. More optimal results are
      received after complete liquidation of residual cavity in different ways and
      suturing of cystobiliary fistulas during operation. For prevention of
      complications related to the presence of residual cavity, laser processing of
      walls of a residual cavity by ozonized 17% hypertonic solution of NaCl was used
      and this procedure showed obvious (p < 0.05) advantages. How to cite this
      article: Aghayev RM. Liver Echinococcosis complicated with Lesions of Bile Ducts
      in Azerbaijan. Euroasian J Hepato-Gastroenterol 2016;6(2):125-130.

PMID- 29201744
TI  - Effects of Age on Liver Enzyme Levels of Obese Men following Moderate-intensity
      Interval Training.
AB  - : The present study aims to consider the effects of age on liver enzyme levels of
      obese men following 15 weeks of moderate-intensity interval training (MIIT). Ten
      obese middle-aged persons (aged 55.2 +/- 4.31 years; height 171.4 +/- 3.59 cm;
      weight 95.7 +/- 14.61 kg; and body mass index [BMI] 32.53 +/- 4.59 kg/m2) and 10
      obese young adults (age 22.7 +/- 1.25 years; height 177.4 +/- 3.94 cm; weight
      100.7 +/- 8.04 kg; and BMI 32 +/- 2.39 kg/m2) were enrolled in this study.
      Interval training was followed by 65 to 75% of VO2max, 1 set, 2 minutes and seven
      repetitions, 1 minute rest-relief interval with 50% of VO2max. Blood sampling was
      carried out in order to measure aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and alkaline phosphatase (ALP). All analyses were
      conducted by Statistical Package for the Social Sciences (SPSS) software (version
      16 for windows). A descriptive statistics including mean and standard deviation
      was obtained for all parameters. Analysis of covariance (ANCOVA) and test of
      normality (Shapiro-Wilk test) were used. Paired sample t-test was used to compare
      the pretest and posttest data in each group. Comparison between middle-aged and
      young adults has shown that MIIT causes significant increase of ALT levels in
      young adults. There is no significant difference between middle-aged and young
      adults on other variables. Also paired sample t-test shows that ALP was decreased
      in both groups. How to cite this article: Rohollah V, Sedigheh K, Yadollah M,
      Rahmatollah K, Mojtaba M. Effects of Age on Liver Enzyme Levels of Obese Men
      following Moderate-intensity Interval Training. Euroasian J Hepato-Gastroenterol
      2016;6(2):131-133.

PMID- 29201745
TI  - Study of Clinicopathological Profile of Sporadic Cases of Colorectal Cancer.
AB  - Objectives: Colorectal cancer (CRC) is the third leading cause of cancer-related
      deaths in the world. This study was carried out to see the epidemiological and
      clinicopathological profile of sporadic cases of CRC in Bangladesh. Materials and
      methods: The patients diagnosed to have colorectal carcinoma in two private
      medical centers of Bangladesh from January 2012 to December 2014 were enrolled in
      this study. Demographic data, clinical presentations, site of lesions, and
      histological types were analyzed. Results: Total 158 patients were included in
      this study. The mean age was 50.77 years and male to female ratio was 1.55:1.
      Rectal bleeding was the commonest symptom irrespective of age and sex followed by
      abdominal pain (33, 20.9%), weight loss (29, 18.3%), abdominal mass (26, 16.4%),
      and altered bowel habit (22, 13.9%). Common histological type was adenocarcinoma
      (156, 98.7%). Conclusion: Colorectal cancer commonly affects males >40 years of
      age. Most common site of involvement is rectum, which is followed by left colon.
      How to cite this article: Saha M, Shil BC, Saha SK, Banik RK, Perveen I,
      Chowdhury MKS, Nazmul Islam ASM, Saifullah ANM. Study of Clinicopathological
      Profile of Sporadic Cases of Colorectal Cancer. Euroasian J Hepato-Gastroenterol
      2016;6(2):134-136.

PMID- 29201747
TI  - Appropriateness of Upper Gastrointestinal Endoscopy: Will the Diagnostic Yield
      Improve by the use of American Society of Gastroenterology Guidelines?
AB  - Aim: Open access endoscopy allows physicians and general practitioners (GIs) to
      refer patients for endoscopy without prior outpatient consultation. This system
      was introduced to reduce waiting time to the procedure and subsequent diagnosis.
      Concerns have been raised regarding misuse of this system with increasing number
      of inappropriate referrals and hence more normal examinations, which has
      implications on a public-funded health system. The aim of this study was to
      assess the appropriate use of the open access system at a rural New Zealand
      hospital and to see if the diagnostic yield improves by following the American
      Society of Gastroenterology (ASGE) guidelines for upper gastrointestinal
      endoscopy [esophagogastroduodenoscopy (OGD)]. Materials and methods: This was a
      prospective study including all the patients who had OGD at Taranaki Base
      Hospital between December 2013 and 2014. A total of 1,019 patients had OGD during
      this time period. The ASGE guidelines were used to see the relationship between
      appropriateness of OGD and finding of a relevant endoscopic diagnosis. Results:
      Fifty-eight percent of the OGDs were judged to be appropriate and 42%
      inappropriate by the explicit criteria. No cancer was found in OGDs judged to be
      inappropriate. Upper gastrointestinal (GI) endoscopies judged appropriate yielded
      significantly more relevant lesions than those judged to be inappropriate [65% vs
      32%; odds ratio 3.94, 99% confidence interval (CI) 2.78, 5.57; p < 0.01].
      Conclusion: The use of ASGE guidelines increases diagnostic yield of OGDs done,
      which is crucial to cost-effectiveness of an open access system and makes the
      system more efficient in selecting and treating patients who need it the most, in
      an acceptable time span. How to cite this article: Tahir M. Appropriateness of
      Upper Gastrointestinal Endoscopy: Will the Diagnostic Yield Improve by the use of
      American Society of Gastroenterology Guidelines? Euroasian J Hepato-Gastroenterol
      2016;6(2):143-148.

PMID- 29201746
TI  - Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in
      Patients with Nonalcoholic Fatty Liver Disease.
AB  - Introduction: In this study, we aimed to investigate the histological and
      clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism
      in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of
      the disease. Materials and methods: Liver function tests, body mass index, waist
      circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c
      (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene
      polymorphism were evaluated in the NAFLD group and control group. The study group
      was evaluated by dividing the group into four subgroups by ACE gene polymorphism
      (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver
      biopsies were evaluated according to Brunt Classification. Results: A total of 31
      patients who were diagnosed with NAFLD and 40 healthy individuals were included
      in the study. The ACE level was found to be 11.69 +/- 1.99 in the NAFLD group and
      11.52 +/- 1.72 in the control group (p = 0.70). There was a negative correlation
      between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical
      parameters were not different among ACE gene polimorphism subgroups, except FBG
      (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in
      terms of grade and stage, no significant difference was found (for stage and
      grade p = 0.68). The ACE gene polymorphism subgroups did not differ by
      histopathologic findings; grade and stage (for grade p = 0.42, for stage p =
      0.92). Conclusion: In this study, we could not find a correlation of ACE and ACE
      gene polymorphism with metabolic risk factors and the disease severity in NAFLD.
      How to cite this article: Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan
      N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE
      Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J
      Hepato-Gastroenterol 2016;6(2):137-142.

PMID- 29201748
TI  - IP-10, p53, and Foxp3 Expression in Hepatocytes of Chronic Hepatitis B Patients
      with Cirrhosis and Hepatocellular Carcinoma.
AB  - Aim: Elucidating differences in gene expression may be useful in understanding
      the molecular pathogenesis and for developing specific markers for the outcome of
      hepatitis B virus (HBV) infection. In the present study, expressions of host gene
      interferon gamma-inducible protein (IP-10), p53, and Foxp3 were studied in
      hepatocytes of patients with chronic HBV infection to determine a possible link
      between selected host gene expression and the outcome of HBV infection. Materials
      and methods: The study was conducted in 60 patients with chronic HBV infection
      and they were divided into four groups: HBV-positive cirrhosis (n = 15), HBV
      negative cirrhosis (n = 15), HBV-positive hepatocellular carcinoma (HCC) (n = 15)
      and HBV-negative HCC (n = 15). Total messenger ribonucleic acid (mRNA) extraction
      was done followed by complementary deoxyribonucleic acid (cDNA) synthesis, and
      finally gene expression was performed using real-time polymerase chain reaction
      (PCR) technique. Results: IP-10 and p53 gene expressions were lower in HBV
      positive cirrhosis, and Foxp3 gene expression was upregulated in HBV-positive
      cirrhosis in comparison to HBV-negative cirrhosis. The expressions of all the
      three genes were upregulated among HBV-positive HCC in comparison to HBV-negative
      HCC. The expression of IP-10, p53, and Foxp3 genes was upregulated in HBV
      positive HCC in comparison to HBV-positive cirrhosis. Conclusion: This study
      indicates that there are variations in the expression of the selected genes among
      cirrhosis and HCC patients with or without HBV. All the three selected genes were
      more or less upregulated in HBV-positive HCC patients, but only Foxp3 expression
      was upregulated in HBV-positive cirrhosis. These three particular genes may have
      a role in the molecular pathogenesis and clinical outcome of HBV-positive
      cirrhosis and HCC patients. These aspects need further evaluation by studies with
      larger numbers of cirrhosis and HCC patients. How to cite this article: Shahera
      U, Munshi S, Jahan M, Nessa A, Alam S, Tabassum S. IP-10, p53, and Foxp3
      Expression in Hepatocytes of Chronic Hepatitis B Patients with Cirrhosis and
      Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2016;6(2):149-153.

PMID- 29201750
TI  - Cost Assessment of Hepatitis B Virus-related Hepatitis in Bangladesh.
AB  - : Hepatitis B virus (HBV) infection is endemic in Bangladesh. Studies have
      indicated that HBV is the major cause of chronic hepatitis B (CHB), liver
      cirrhosis (LC), and hepatocellular carcinoma (HCC) in this country. Recently, HBV
      related acute on chronic liver failure (HBV-ACLF) has emerged as a serious and
      emergent medical problem in Bangladesh. To develop a strategy to address HBV
      related problems and their influence on health care delivery system, proper
      understandings about extent of problems and nature of economic burden should be
      explored. Conservative estimates indicate that about 50 million or more of
      Bangladeshi have been infected by HBV at some point of their life. Out of the
      total Bangladeshi population, about 2 to 5% is chronically infected with HBV
      (about 3-8 million) (1-6%) and considerable number of these patients will
      eventually develop LC, HCC, or ACLF (about 1 million). Although proper statistics
      is lacking, it is estimated that HBV-related liver diseases account for a
      majority of hospital admissions and around 20,000 deaths every year in
      Bangladesh. In addition, complex clinical features of HBV-related liver diseases
      have been documented in Bangladesh that show similarity and differences from HBV
      infection in other Asian countries. Although vaccination against HBV and
      containment of horizontal transmission are in progress in Bangladesh for
      reduction of new HBV infection, there is a lack of national strategy for
      treatment of millions of chronic HBV-infected subjects. This paper will provide
      an insight regarding the economic impact of HBV in Bangladesh that may act as a
      primary impetus for developing national HBV eradication program, a goal set by
      World Health Organization (WHO). How to cite this article: Al Mahtab M, Chaudhury
      M, Uddin MH, Noor-E-Alam SM, Rahim MA, Alam MA, Moben AL, Khondaker FA, Choudhury
      MFI, Sarkar MJA, Poddar PK, Foez SA, Akbar SMF. Cost Assessment of Hepatitis B
      Virus-related Hepatitis in Bangladesh. Euroasian J Hepato-Gastroenterol
      2016;6(2):163-166.

PMID- 29201749
TI  - Nonalcoholic Fatty Liver Disease in South Asia.
AB  - : Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease in the West, and is also increasing alarmingly in South Asia, reaching an
      epidemic proportion of 30% because of epidemic of obesity and metabolic syndrome
      (MS) in younger South Asians in the last two decades. Prevalence of MS and fatty
      liver is escalating in geometric progression in South Asian countries, such as
      India, Pakistan, Sri Lanka, Bangladesh, Nepal, Bhutan, Burma, and Maldives
      because of sedentary lifestyle, poor health awareness, socioeconomic growth,
      affluence, urbanization, and dietary westernization. Almost 20% of world's
      population resides in South Asia, making it the most populous and most densely
      populated geographic region in the world, thereby having most of MS and NAFLD
      cases within its territory. The risk factors and course of NAFLD do not differ
      between South Asians and other ethnic populations, but the obesity epidemic is
      more recent in South Asia than elsewhere in the world. Nonalcoholic fatty liver
      disease may progress through stages of simple bland steatosis, nonalcoholic
      steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and finally hepatocellular
      carcinoma (HCC). It is frequently associated with obesity, MS, dyslipidemia,
      insulin resistance (IR), and type-2 diabetes mellitus (DM). Nonalcoholic fatty
      liver disease is frequently diagnosed with abdominal ultrasonography (US) study.
      Despite its high prevalence in the community till now, no definitive
      pharmacotherapy is available for NAFLD. However, modification of risk factors,
      such as dyslipidemia, control of diabetes, and weight reduction do help to some
      extent. The nonobese South Asians are also at increased risk of having NAFLD and
      NASH as, despite of absence of frank obesity in South Asians, they are
      metabolically more obese compared to other ethnic population and more prone to
      develop NAFLD-related complications. Therefore, the cost-effective US abdomen
      should be included in the list of tests for persons undergoing preemployment or
      master health checkups for early diagnosis of NAFLD in this resource-constraint
      South Asian region, so that early necessary measures can be undertaken to reduce
      NAFLD associated morbidity and mortality in the community. How to cite this
      article: Pati GK, Singh SP. Nonalcoholic Fatty Liver Disease in South Asia.
      Euroasian J Hepato-Gastroenterol 2016;6(2):154-162.

PMID- 29201751
TI  - A Case of Biliary Peritonitis following Spontaneous Common Bile Duct Perforation
      in a Child.
AB  - : Spontaneous common bile duct (CBD) perforation leading to biliary peritonitis
      is a rare entity in children. It is an unusual cause of acute abdomen and is
      potentially fatal. Preoperative diagnosis is rare. A 10-year-old girl was
      referred from a private hospital after laparotomy for acute abdomen.
      Intraoperatively, bile was found in the peritoneal cavity which was drained, and
      the patient was referred to Topiwala National Medical College. Endoscopic
      retrograde cholangiopancreaticography (ERCP) and stenting was done. The stent was
      removed after 8 weeks, and the girl is doing well during follow-up. How to cite
      this article: Sharma C, Desale J, Waghmare M, Shah H. A Case of Biliary
      Peritonitis following Spontaneous Common Bile Duct Perforation in a Child.
      Euroasian J Hepato-Gastroenterol 2016;6(2):167-169.

PMID- 29201752
TI  - A Case of Early detected Multidrug-resistant Acinetobacter baumannii Infection
      after Liver Transplantation.
AB  - : Invasive bacterial infections have become the leading cause of morbidity and
      mortality among solid organ transplant recipients (SOTRs). Acinetobacter
      baumannii can cause a serious infection in SOTRs. Multidrug-resistant A.
      baumannii (MDR-Ab) represents a major problem in liver transplant recipients.
      Here, we presented a respiratory infection related to MDR-Ab pathogenesis in a
      patient who underwent liver transplantation due to acute hepatic failure.
      Accordingly, it has been emphasized that infections after the liver
      transplantation should be accomplished after due consideration of all relevant
      facts with a multidisciplinary approach. How to cite this article: Balkan A,
      Balkan Y, Mete AO. A Case of Early detected Multidrug-resistant Acinetobacter
      baumannii Infection after Liver Transplantation. Euroasian J Hepato-Gastroenterol
      2016;6(2):170-172.

PMID- 29201753
TI  - How to approach Incidentally detected Gastrointestinal Stromal Tumor during
      Laparoscopic Sleeve Gastrectomy: A Report of Two Cases.
AB  - : Laparoscopic sleeve gastrectomy (LSG) is a frequently used bariatric surgery
      method. It is possible to incidentally detect gastrointestinal stromal tumors
      (GISTs) of stomach or other gastric tumors during this procedure. In the
      literature, there is limited data about cooccurrence of GIST in obesity, and
      treatment of such cases is still controversial. On the contrary, currently
      accepted treatment of local and nonmetastatic GIST cases is surgery alone, and of
      cases with systemic disease is surgery combined with imatinib mesylate therapy.
      Incidental detection of GIST during bariatric surgery may require a modification
      in the planned procedure, and an extensive exploration and picking a convenient
      surgical procedure will become necessary. Here, we present two cases - a gastric
      GIST and a GIST of small intestine - both of which were incidentally detected
      during LSG performed for obesity. How to cite this article: Atas H, Bulus H,
      Akkurt G, Yavuz A, Tantoglu U, Alimogullari M, Aydin A. How to approach
      Incidentally detected Gastrointestinal Stromal Tumor during Laparoscopic Sleeve
      Gastrectomy: A Report of Two Cases. Euroasian J Hepato-Gastroenterol
      2016;6(2):173-175.

PMID- 29201754
TI  - Complete Eradication of Bleeding Duodenal Varices with Endoscopic Polydocanol
      Sclerotherapy.
AB  - : Bleeding from duodenal varices is a rare complication of portal hypertension,
      occurring in only 0.4% of these patients and is often life-threatening because of
      the difficulty in diagnosis and treatment. Treatment options include surgical
      procedures and endoscopic and endovascular treatments. A 48-year-old female
      cirrhotic patient was admitted to our clinic with upper gastrointestinal (GI)
      tract bleeding. Endoscopic examination revealed nonbleeding Lm, Cb, RC (+), F3-F3
      F2 esophageal and nodular-bleeding-oozing duodenal varices. Esophageal varices
      were eradicated with band ligation at two sessions. After one session of 2%
      polydocanol sclerotheraphy, no signs of bleeding were determined. Complete
      eradication was achieved after five sessions and 1 year apart from the initial
      treatment duodenal varices were eradicated. Although duodenal varices are rare,
      they are frequently fatal. There are limited data regarding optimal treatment.
      Successful treatment depends both on patient factors (hepatic synthetic function,
      comorbidities, size/location of the varices) and center expertise. Long-term
      eradication is variable and may depend on the cause and extensiveness of the
      ectopic varices. How to cite this article: Temel T, Aktas A, Ozgenel SM, Ozakyol
      A. Complete Eradication of Bleeding Duodenal Varices with Endoscopic Polydocanol
      Sclerotherapy. Euroasian J Hepato-Gastroenterol 2016;6(2):176-178.

PMID- 29201755
TI  - A Rare Cause of Acute Abdomen: Diagnosis and Management of Adult Colonic
      Intussusception.
AB  - : Intussusception in adults is very rarely seen, and this cause acute abdomen. A
      computed tomography (CT) scan, clinical suspicion, history, and a physical
      examination are important for the diagnosis. We present two cases of colonic
      intussusceptions induced by lipoma. The cases had similar locations, diagnoses,
      and management. Both lipomas were located close to the cecum in the ascending
      colon, and a right segmental colon resection was performed in both cases. The
      follow-up of both cases was uneventful. Although benign lesions can cause colonic
      intussusception, the high incidence of malignancy in colonic lesions should
      always be considered. Therefore, oncologic surgical procedures should be applied.
      The definitive diagnosis can be made by histopathology. How to cite this article:
      Sertkaya M, Emre A, Pircanoglu EM, Yazar FM, Tepe M, Cengiz E, Isler A, Vicdan H.
      A Rare cause of Acute Abdomen: Diagnosis and Management of Adult Colonic
      Intussusception. Euroasian J Hepato-Gastroenterol 2016;6(2):179-182.

PMID- 29201756
TI  - Abdominal Inflammatory Myofibroblastic Tumor: A Rare Case.
AB  - : An inflammatory myofibroblastic tumor, also known as inflammatory pseudotumor,
      is a rare neoplasm characterized by myofibroblastic spindle and inflammatory
      cells that cause masses in many sites of body. It is often benign, but in some
      cases neoplastic transformation has been reported as a result of aggressive
      growing. In our case, an inflammatory myofibroblastic tumor was reported by
      biopsy of a 25 * 15 cm abdominal mass. How to cite this article: Tastekin F,
      Ersoy M, Temel T, Ozgenel SM, Canaz F, Ozakyol A. Abdominal Inflammatory
      Myofibroblastic Tumor: A Rare Case. Euroasian J Hepato-Gastroenterol
      2016;6(2):183-185.

PMID- 29201757
TI  - Giant Appendicular Mucocele Due to Mucinous Cystadenoma.
AB  - : Mucocele of the appendix is a rare clinicopathological entity simulating acute
      appendicitis. The most common form of the mucocele is cystadenoma, which is
      characterized by luminal dilatation producing large amounts of mucin. We present
      a new case of a giant mucocele of appendix with mucinous cystadenoma. A 61-year
      old female was admitted with complaints of severe lower right quadrant pain.
      Ultrasonography and computed tomography (CT) suggested that it was a mucocele,
      but due to severity of pain, she underwent an emergency operation. Fortunately,
      without a perforation, it was a giant mucocele and the operation was terminated
      with an uneventful appendectomy with segmental cecal resection. The
      histopathological evaluation of the specimen reported to be a mucocele with
      mucinous cystadenoma with negative surgical margins. The patient was discharged
      postoperative 6th day, and a control colonoscopy and abdominal CT was planned for
      6 months following surgery. Appendicular mucocele is rare and difficult to
      diagnose preoperatively, and sometimes it may be of large size which increases
      the risk of perforation. Pseudomyxoma peritonei (PP) is the most feared
      complication of mucocele perforation. Appendectomy with negative margins is a
      requirement for adequate treatment for most cases. Utmost care should be taken
      during surgery to avoid perforation of mucocele. How to cite this article:
      Sertkaya M, Emre A, Pircanoglu EM, Peker O, Cengiz E, Karaagac M. Giant
      Appendicular Mucocele Due to Mucinous Cystadenoma. Euroasian J Hepato
      Gastroenterol 2016;6(2):186-189.

PMID- 29201758
TI  - A Case of Severe Ulcerative Colitis with Colonic Dilatation caused by Renal
      Mucinous Tubular and Spindle Cell Carcinoma.
AB  - : We present a case of ulcerative colitis (UC) in a patient during the first
      severe relapse with colonic dilatation and coexisting of giant renal tumor.
      Kidney tumor was constricting on colon and imitating toxic megacolon (TM). The
      patient with severe acute colitis (SAC) was admitted to the Department of
      Gastroenterology and Hepatology with inflammatory bowel disease (IBD) diagnosed
      in the previous month, based on clinical symptoms, endoscopy, and histopathology
      results. Computed tomography (CT) revealed a giant left kidney tumor without
      evidence of infiltration, a dilatation of the transverse colon up to 6 cm, and
      narrow light of the descending colon. There were no signs of intestinal
      obstruction or perforation. The control X-rays revealed maintaining megacolon,
      with dilatation of splenic flexure projection up to 6.5 to 7.5 cm. The patient
      was treated conservatively with no apparent improvement and finally operated on.
      Intraoperatively, a large tumor of the kidney (12 cm) constricting intestine was
      revealed. Left-sided nephrectomy and partial resection of the colon with the
      emergence of a colostomy was performed. The histopathology exam revealed renal
      mucinous tubular and spindle cell carcinoma (RMTSCC), a very rare malignant
      kidney tumor of low malignant potential and relative good prognosis. It was
      identified in the past 20 years. To date, approximately 100 such cases of cancer
      have been described. How to cite this article: Kukulska M, Smola I, Halon A,
      Paradowski L, Poniewierka E, Kempinski R, Annabhani A. A Case of Severe
      Ulcerative Colitis with Colonic Dilatation caused by Renal Mucinous Tubular and
      Spindle Cell Carcinoma. Euroasian J Hepato-Gastroenterol 2016;6(2):190-193.

PMID- 29201759
TI  - Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder to cause
      Chronic Liver Disease.
AB  - : The Budd-Chiari syndrome (BCS) is a rare disorder due to chronic liver disease
      (CLD), which is caused by the obstruction of hepatic venous outflow that can be
      located at any place from the small hepatic venules up to the entrance of the
      inferior vena cava (IVC) into the right atrium. Among the causes of BCS, the
      rarer one is coagulation factor deficiencies. Here, we report a case of BCS
      associated with deficiency of protein C resulting in thrombus in IVC. The patient
      was a 50-year-old male, who had been suffering from recurrent abdominal and leg
      swelling for a long period of 7 years. He was evaluated thoroughly, and other
      causes of liver cirrhosis were excluded. How to cite this article: Begum R, Al
      Mahtab M, Al Mamun A, Moben AL, Hossain SMS, Das DC, Malakar D, Rashid HO, Roy
      PP, Rahman S. Budd-Chiari Syndrome Due to Protein C Deficiency: A Rare Disorder
      to cause Chronic Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):194
      197.

PMID- 29201760
TI  - Embryonal Testicular Cancer with Duodenal Metastasis: Could Nausea and Vomiting
      be Alarm Symptoms?
AB  - Aim: Duodenal metastasis of testicular cancer is an uncommon condition in
      clinical practice. Here, we have reported a case of this nature. Background:
      Testicular cancers are among the most seen cancer types among young men.
      Metastasis of testicular cancer generally occurs through hematogenous and
      lymphatic drainage. Gastrointestinal (GI) metastasis of testicular cancer has
      been reported rarely. Case report: A duodenal mass was seen in
      esophagogastroduodenoscopic examination in a man who was admitted into hospital
      for medical treatment of resistant nausea and vomiting. He was previously
      diagnosed with testicular cancer. Computed tomography (CT) views were compatible
      with primary duodenal tumor. The duodenal mass was compatible with germ cell
      neoplasm metastasis. He received chemotherapy regime which includes cisplatin,
      paclitaxel, and ifosfamid. Nausea and vomiting symptoms decreased and metastatic
      mass and lymph nodes were regressed. Conclusion: Duodenum metastasis of
      testicular cancer can be treated with a chemotherapy regimen, and patients can
      improve radiologically and symptomatically without the need of any surgery.
      Physicians should keep in mind that GI metastasis of testicular cancer may
      present with nausea and vomiting symptoms. How to cite this article: Duygulu ME,
      Kaymazli M, Goren I, Yildirim B, Sullu Y, Nural MS, Bektas A. Embryonal
      Testicular Cancer with Duodenal Metastasis: Could Nausea and Vomiting be Alarm
      Symptoms? Euroasian J Hepato-Gastroenterol 2016;6(2):198-201.

PMID- 29201761
TI  - Biochemical Scoring System for diagnosing Nonalcoholic Steatohepatitis.
AB  - Noor-E-Alam M, Alam S, Alam AKMK, Al Mahtab M, Rahman S. Biochemical Scoring
      System for diagnosing Nonalcoholic Steatohepatitis. Euroasian J Hepato
      Gastroenterol 2016;6(2):202-204.

PMID- 29201762
TI  - Editorial.

PMID- 29201763
TI  - Role of Clinical, Biochemical, and Imaging Parameters in predicting the Severity
      of Acute Pancreatitis.
AB  - Aim: The assessment of the severity of acute pancreatitis (AP) is important for
      proper management of the disease and for its prognosis. The aim was to correlate
      clinical, biochemical, and imaging diagnostic parameters and evaluate their
      prognostic values in the early assessment of severity of AP. Materials and
      methods: We prospectively studied 128 consecutive patients with AP. The
      predictors were clinical, biochemical, and imaging diagnostic parameters. The
      outcome measure was the occurrence of complications. Abdominal sonogram, contrast
      enhanced computer tomography, and pancreatitis-specific clinical and laboratory
      findings were done. Results: According to the Atlanta classification, 84 patients
      (65.6%) had mild and 44 (34.4%) had severe AP. The severity markers were
      significantly different between the mild and the severe groups (p < 0.001).
      Leukocyte count, serum albumin level, C-reactive protein (CRP), Ranson, acute
      physiology and chronic health evaluation II (APACHE II), and Glasgow score were
      the factors associated with radiological severity grade. Leukocyte count, CRP,
      Ranson score, APACHE II, and Glasgow score were the factors associated with the
      number and appearance of acute fluid collections (AFCs). A significant
      association was found between the number of AFCs and the occurrence of
      complications [odds ratio 4.4; 95% confidence interval 2.5-7.6]. Hospital stay
      was significantly longer in the group with severe disease as compared with the
      group with mild disease (p < 0.001). Conclusion: Clinical, biochemical, and
      imaging diagnostic parameters are related to the clinical course of AP and they
      can predict its severity. This allows us to determine the severity of the disease
      and to target the patients with high scores for close monitoring and more
      aggressive intervention.How to cite this article: Zerem D, Zerem O, Zerem E. Role
      of Clinical, Biochemical, and Imaging Parameters in predicting the Severity of
      Acute Pancreatitis. Euroasian J Hepato-Gastroenterol 2017;7(1):1-5.

PMID- 29201764
TI  - Predictive Value of Mean Platelet Volume in Variceal Bleeding due to Cirrhotic
      Portal Hypertension.
AB  - Aim: To investigate whether mean platelet volume (MPV) is a predictor of variceal
      bleeding in patients with cirrhotic portal hypertension. Materials and methods:
      This prospective cohort was performed in the internal medicine department of our
      tertiary care center. Cirrhotic patients were allocated into two groups: Group I
      consisted of 31 cases without a history of variceal bleeding, whereas group II
      was made up of 31 patients with a history of variceal bleeding. Data derived from
      medical history, physical examination, ultrasonography, gastrointestinal system
      endoscopy, complete blood count, hepatic, and renal function tests were recorded
      and compared between two groups. On physical examination, encephalopathy and
      ascites were evaluated and graded with respect to Child-Pugh-Turcotte
      classification. Results: There was no significant difference between the two
      groups in terms of age, duration of the disease, and gender of the patient. The
      only remarkable difference was that hemoglobin (p = 0.02) and hematocrit (p =
      0.02) values were lower in group II. Neither the etiology of bleeding was
      different between groups nor did MPV seem to have a noteworthy impact on
      bleeding. Interestingly, risk of variceal bleeding increased in parallel to the
      higher grade of varices. Conclusion: Our results imply that there is a
      correlation between the grade of varices and esophageal vari-ceal bleeding in
      cirrhotic patients. However, association between MPV and variceal bleeding could
      not be demonstrated. Utilization of noninvasive tests as predictors in these
      patients necessitates further controlled trials on larger series.How to cite this
      article: Erdogan MA, Benli AR, Acmali SB, Koroglu M, Atayan Y, Danalioglu A,
      Kayhan B. Predictive Value of Mean Platelet Volume in Variceal Bleeding due to
      Cirrhotic Portal Hypertension. Euroasian J Hepato-Gastroenterol 2017;7(1):6-10.

PMID- 29201765
TI  - Association of Severity of Helicobacter pylori Infection with Peripheral Blood
      Neutrophil to Lymphocyte Ratio and Mean Platelet Volume.
AB  - Aim: To determine the correlation of Helicobacter pylori infection with
      peripheral blood neutrophil/lymphocyte ratio (NLR) and mean platelet volume
      (MPV). Materials and methods: The NLR, MPV, platelets, leukocytes, neutrophils,
      and lymphocytes were calculated and the differences between groups were
      investigated. Results: A total of 199 patients were included in the study.
      Neutrophil/lymphocyte ratio was statistically lower in H. pylori-positive
      patients than in H. pylori-negative patients (1.94 +/- 0.79 vs 2.67 +/- 2.35
      respectively, p = 0.04). There was no significant difference between H. pylori
      negative patients and H. pylori-positive patients of severe intensity in terms of
      MPV. However, peripheral blood lymphocytes and platelets were statistically
      significantly higher in H. pylori-positive patients of severe intensity
      (lymphocytes 2150 +/- 826 vs 2954 +/- 2436 respectively, p = 0.000 and platelets
      258247 +/- 69494 vs 265611 +/- 113397 respectively, p = 0.02) compared with H.
      pylori-negative patients. Conclusion: A moderate increase in the intensity of H.
      pylori does not lead to a significant change in MPV as measured by hemogram;
      however, it gives rise to a statistically significant fall in NLR. Presence of
      severe H. pylori-positive intensity leads to a statistically significant increase
      in peripheral blood lymphocytes and platelets compared with H. pylori-negative
      patients.How to cite this article: Guclu M, Agan AF. Association of Severity of
      Helicobacter pylori Infection with Peripheral Blood Neutrophil to Lymphocyte
      Ratio and Mean Platelet Volume. Euroasian J Hepato-Gastroenterol 2017;7(1):11-16.

PMID- 29201766
TI  - Are Synbiotics added to the Standard Therapy to eradicate Helicobacter pylori in
      Children Beneficial? A Randomized Controlled Study.
AB  - Aim: We aimed to evaluate the role of the addition of Bifidobacterium /actis
      containing synbiotic to the triple therapy in the case of He/icobacter py/ori
      eradication, the dyspeptic symptoms, and reducing the side effects of
      antibiotics. Materials and methods: A total of 104 children aged between 5 and 17
      years, who were histopathologically diagnosed with H. py/ori were enrolled in
      this study, of whom 100 were included in the analysis. Patients were randomly
      classified into two groups. In the first group, 50 patients were administered
      amoxicillin + clarithromycin + lansoprazole for 14 days and B. /actis-containing
      synbiotic. In the second group, 50 patients were treated with the standard triple
      therapy. All patients were given information after completion of therapy.
      Results: H. py/ori eradication was achieved in 88% in group I who received
      standard therapy with additional synbiotic and 72% in group II (p = 0.046). The
      number of patients in the second group who suffered from abdominal pain between
      the 3rd and 14th day of the treatment was higher (p < 0.05). The addition of
      probiotics to the triple therapy significantly reduced the frequency of diarrhea,
      but no significant difference was detected in the frequency of metallic taste (p
      = 0.04, p = 0.418 respectively). Conclusion: The addition of synbiotic to the
      triple therapy is effective for eradicating H. py/ori infection in children and
      is usually helpful to reduce or eliminate dyspeptic symptoms like abdominal pain,
      diarrhea, and vomiting. This study suggest that improved tolerance to the
      eradication treatment also reduces the treatment failure by adding probiotics and
      encourages the future study using probiotic supplementation in H. py/ori
      treatment.How to cite this article: Sirvan BN, Usta MK, Kizilkan NU, Urganci N.
      Are Synbiotics added to the Standard Therapy to eradicate He/icobacter Py/ori in
      Children Beneficial? A Randomized Controlled Study. Euroasian J Hepato
      Gastroenterol 2017;7(1):17-22.

PMID- 29201767
TI  - Management of Liver Abscess in Children: Our Experience.
AB  - Introduction: Liver abscess is common in pediatric population in India. Children
      have unique set of predisposing factors and clinical features. Liver abscesses
      are infectious, space-occupying lesions in the liver; the two most common
      abscesses being pyogenic and amebic. Its severity depends on the source of the
      infection and the underlying condition of the patient. Materials and methods: A
      total of 34 patients less than 12 years were assessed in a retrospective study
      from January 2012 to 2016. Patients were assessed in terms of age of
      presentation, etiology, bacteriology, diagnosis, and modality of treatment.
      Results: The mean age of presentation was 6.3 years. Average volume of abscess
      was 164 cc. Nine patients (26.4%) underwent percutaneous needle aspiration under
      ultrasound guidance with wide bore needle (18 G disposable needle). Three
      patients required more than two sittings of aspiration. Patients with volume more
      than 80 cc were treated with catheter drainage. Twenty patients (58.8%) underwent
      ultrasound-guided percutaneous catheter drainage. Two patients required catheter
      drainage for large abscess and needle aspiration for the smaller abscess.
      Conclusion: Antimicrobial therapy along with percutaneous drainage constitutes
      the mainstay of treatment, whereas open surgical drainage should be reserved for
      selected cases.How to cite this article: Waghmare M, Shah H, Tiwari C, Khedkar K,
      Gandhi S. Management of Liver Abscess in Children: Our Experience. Euroasian J
      Hepato-Gastroenterol 2017;7(1):23-26.

PMID- 29201768
TI  - Prediction of Sustained Virological Response to Peginterferon-based Therapy for
      Chronic Hepatitis C: Regression Analysis of a Cohort from Rio Grande do Sul,
      Brazil.
AB  - Aim: Peginterferon plus ribavirin (peg-IFN/RBV) is still the standard of care for
      treatment of hepatitis C virus (HCV) in many countries. Given the high toxicity
      of this regimen, our study aimed to develop a prediction tool that can identify
      which patients are unlikely to benefit from peg-IFN/RBV and could thus postpone
      treatment in favor of new-generation direct-acting antivirals. Materials and
      methods: Binary regression was performed using demographic, clinical, and
      laboratory covariates and sustained virological response (SVR) outcomes from a
      prospective cohort of individuals referred for therapy from 2003 to 2008 in a
      public HCV treatment center in Rio Grande do Sul, Brazil. Results: Of the 743
      participants analyzed, 489 completed 48 weeks of treatment (65.8%). A total of
      202 of those who completed peg-IFN/RBV therapy achieved SVR (27.2% responders),
      196 did not (26.4%), and 91 had missing viral load (VL) at week 72 (12.2% loss to
      follow-up). The remainder discontinued therapy (n = 254 [34.2%]), 78 (30.7%)
      doing so due to adverse effects. Baseline covariates included in the regression
      model were sex, age, human immunodeficiency virus, infection status, aspartate
      transaminase, alanine transaminase, hemoglobin, platelets, serum creatinine,
      prothrombin time, pretreatment VL, cirrhosis on liver biopsy, and treatment
      naivety. A predicted SVR of 17.9% had 90.0% sensitivity for detecting true
      nonresponders. The negative likelihood ratio at a predicted SVR of 17.9% was
      0.16, and the negative predictive value was 92.6%. Conclusion: Easily obtainable
      variables can identify patients that will likely not benefit from peg-IFN-based
      therapy. This prediction model might be useful to clinicians. Clinical
      significance: To our knowledge, this is the only prediction tool that can
      reliably help clinicians to postpone peg-IFN/RBV therapy for HCV genotype 1
      patients.How to cite this article: Picon RV, Fendt L, Amaral K, Picon PD.
      Prediction of Sustained Virological Response to Peginterferon-based Therapy for
      Chronic Hepatitis C: Regression Analysis of a Cohort from Rio Grande do Sul,
      Brazil. Euroasian J Hepato-Gastroenterol 2017;7(1):27-33.

PMID- 29201770
TI  - Elimination of Hepatitis Viruses: Bangladesh Scenario.
AB  - The World Health Organization (WHO) has adopted targets unanimously at the World
      Health Assembly in July 2016, in Geneva, to significantly curtail hepatitis B and
      C viruses to near extinction by 2030. Preparations are now ongoing in all WHO
      member nations across the globe to reach this ambitious, but perhaps achievable
      target. In Bangladesh, hepatologists, nongovernmental organizations, civil
      society, and patients have joined hands with the government in this global fight
      against viral hepatitis. How to cite this article: Mahtab MA. Elimination of
      Hepatitis Viruses: Bangladesh Scenario. Euroasian J Hepato-Gastroenterol
      2017;7(1):40-42.

PMID- 29201769
TI  - Epidemiology, Diagnosis, and Risk Factors of Helicobacter pylori Infection in
      Children.
AB  - H. pylori infection is a global public health problem associated with some
      gastrointestinal diseases in children, especially in developing countries, since
      prevalence of H. pylori is low in the developed world. Both noninvasive (stool
      antigen test, urea breath test, and blood test) and invasive (histology, rapid
      urease test, and microbiological culture) tests have been utilized to detect H.
      pylori infection. However, a single test is not reliable enough and does not
      provide accurate enough data to determine H. pylori infection among children.
      Risk factors of H. pylori infection in children were related to ethnicities,
      household properties, geographic location, living conditions, water sources, type
      of housing, presence/absence of sewage systems, and garbage collection within the
      living environment. These risk factors were usually associated with the
      socioeconomic status of the family. This review article aims to determine the
      gaps in the knowledge of the epidemiology, risk factors, and diagnostic tests of
      H. pylori infection among children. How to cite this article: Ozbey G, Hanafiah
      A. Epidemiology, Diagnosis, and Risk Factors of Helicobacter pylori Infection in
      Children. Euroasian J Hepato-Gastroenterol 2017;7(1):34-39.

PMID- 29201771
TI  - Immunization against Viral Hepatitis B: Lessons Learnt from Kingdom of Cambodia.
AB  - An account of immunization against hepatitis B virus in Cambodia is given. How to
      cite this article: Sreng B, Vichit O, Vuthikol Y, Aun C, Samnang C. Immunization
      against Viral Hepatitis B: Lessons Learnt from Kingdom of Cambodia. Euroasian J
      Hepato-Gastroenterol 2017;7(1):43-47.

PMID- 29201772
TI  - Managing Encephalopathy in the Outpatient Setting.
AB  - In cirrhosis of liver, hepatic encephalopathy (HE) has an important impact on
      health-related quality of life. It is important to define whether HE is episodic,
      recurrent, or persistent; types A, B, or C; overt HE or covert HE; and
      spontaneous or precipitated. The overt HE is clinically evident and needs
      hospitalization. Nonabsorbable disaccharides, rifaximin, and probiotics are
      proven to be useful in the treatment of overt HE. Covert HE includes both minimal
      HE and grade I HE. It is not apparent on routine clinical examination. Presence
      of poor work productivity, increased accidental injuries on complex machinery and
      driving, etc., raise the suspicion of cognitive dysfunction. Specialized
      neurocognitive testing like psychometric HE, computerized tests like critical
      flicker frequency tests, inhibitory control tests, Stroop encephalopathy tests,
      and electroencephalography are needed to diagnose overt HE. Various studies have
      shown lactulose and rifaximin to be useful in overt HE. However, presence of
      persistent and recurrent HE in cirrhosis is an indication for liver transplant.
      Lactulose is effective both in improving reversal of minimal HE and in reducing
      the risk of development of overt HE. How to cite this article: Gupta T, Rathi S,
      Dhiman RK. Managing Encephalopathy in the Outpatient Setting. Euroasian J Hepato
      Gastroenterol 2017;7(1):48-54.

PMID- 29201773
TI  - Epidemiology of Hepatitis B and C in Republic of Indonesia.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections pose serious
      problems in terms of public health and clinical intervention in a country with
      approximately 250 million people, who live in more than 17,000 islands. Efforts
      to combat HBV and HCV have been made through the implementation of universal
      infant hepatitis B immunization, blood screening, and other health promotion
      actions, and building epidemiological data to develop intervention strategies. A
      nationwide study in 2013 revealed hepatitis B surface antigen (HBsAg) prevalence
      of 7.1%, which indicates that Indonesia has moved from high to moderate
      endemicity of hepatitis B, leaving the prevalence of 9.4% in 2007. The
      occurrences of new hepatitis B cases still continue in early childhood period,
      which may root from low coverage of birth-dose hepatitis B immunization in remote
      islands, and the potential mother-to-child transmission of HBV from HBsAg
      positive pregnant mothers. Other problems still exist including the high HBV
      infection rates among young adults in remote islands, the presence of occult
      hepatitis B, as well as the substantial prevalence of HCV infection in general
      population, who do not have access to diagnosis and treatment. Effective
      preventive and control strategies are being developed tailored to the local
      capacity, infrastructures, socioeconomics, and culture, as well as geographical
      aspects of the country. How to cite this article: Muljono DH. Epidemiology of
      Hepatitis B and C in Republic of Indonesia. Euroasian J Hepato-Gastroenterol
      2017;7(1):55-59.

PMID- 29201774
TI  - Hepatitis Action Plan and Changing Trend of Liver Disease in Japan: Viral
      Hepatitis and Nonalcoholic Fatty Liver Disease.
AB  - In Japan, the estimated number of chronic hepatitis B virus infections was 1.1 to
      1.4 million, and that of chronic hepatitis C virus was 1.9 to 2.3 million in
      2000. The mortality of hepatocellular carcinoma had been increasing and hit the
      peak at around 2002, which subsequently started to decrease. Japan has a national
      action plan for addressing viral hepatitis called Basic Act on Hepatitis
      Measures, established in 2009. In 2011, basic guidelines for promotion of control
      measures for hepatitis were issued, comprising nine principles in order to
      promote measures to prevent hepatitis B and C. According to these guidelines,
      national and local governments share screening costs for testing hepatitis B and
      C in residents who are over 40 years old. Thus, out-of-pocket expenses from
      examinees are nil or reduced to the minimum. In addition, for patients with
      chronic hepatitis B or C and on treatment, drug prices of nucleotide analogs,
      interferon (IFN) treatment, or IFN-free direct antiviral agents along with
      examination expenses should be covered by special programs for viral hepatitis.
      The national and local governments cover the amount in excess of 100 to 200 USD
      of the cost of treatment. The proportion of liver cancer with nonviral etiology
      has been increasing in Japan. For the screening and follow-up of patients with
      nonalcoholic fatty liver disease, we demonstrated that interleukin 34 is a
      feasible fibrosis marker. Several advantages have prevailed in the Japanese
      health care systems for patients with viral liver disease compared with those in
      countries in the Western Pacific region. Therefore, Japan should take a lead in
      helping the implementation of practical hepatitis action plans in every country
      when in need. How to cite this article: Kanto T, Yoshio S. Hepatitis Action Plan
      and Changing Trend of Liver Disease in Japan: Viral Hepatitis and Nonalcoholic
      Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2017;7(1):60-64.

PMID- 29201775
TI  - Chronic Viral Hepatitis in Malaysia: "Where are we now?"
AB  - Malaysia is a country where an estimated 1 million people are chronically
      infected with hepatitis B virus (HBV) and an estimated 2.5% of the adult
      population are positive for antibody to hepatitis C virus (HCV). Effective
      nationwide vaccine coverage seems to be a highly effective measure to prevent new
      HBV infection. Treatment of HCV infection is also a regular practice in Malaysia.
      These measures highlight the possibility to reach the World Health Organization
      elimination target by 2030. To achieve this target, the Health Ministry and other
      nongovernmental organizations, such as My Commitment to Cure (MyC2C) are working
      together to develop a strategic road map to reach the global elimination target
      in Malaysia by 2030. How to cite this article: Raihan R, Mohamed R, Hasan MRA,
      Rosaida MS. Chronic Viral Hepatitis in Malaysia: "Where are we now?" Euroasian J
      Hepato-Gastroenterol 2017;7(1):65-67.

PMID- 29201777
TI  - Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of
      Antivirals.
AB  - Hepatitis E virus (HEV) infection results in nearly 20 million new infections,
      resulting in 70,000 deaths globally each year. Previously thought as a disease
      limited to developing nations with poor sanitation and hygiene, it is
      increasingly recognized that even the most developed nations are not spared. A
      clear dichotomy in epidemiology of HEV is noted between developing and
      industrialized nations. The HEV genotypes 1 and 2 are common in Asia and Africa
      and are transmitted mainly by contaminated drinking water. Sporadic as well as
      large-scale epidemics of acute hepatitis have been noted with HEV genotype 1
      infection in developing countries of Asia and Africa. On the contrary, HEV
      genotypes 3 and 4 are common in industrialized nations and unlike genotypes 1 and
      2, they are transmitted by consumption of raw meat products, fruits, and blood
      transfusion. Large epidemics have not been reported with HEV genotypes 3 and 4
      and manifestation is usually indolent, though severe acute hepatitis has been
      reported. How to cite this article: Shrestha A, Gupta BP, Lama TK. Current
      Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals.
      Euroasian J Hepato-Gastroenterol 2017;7(1):73-77.

PMID- 29201776
TI  - Viral Hepatitis and Liver Diseases in Mongolia.
AB  - Mongolia is known for its high endemicity for viral hepatitis. Previous studies
      report that the seroprevalence of hepatitis B virus (HBV) is 11.8% (178/1,512)
      among the unvaccinated population in 13 provinces and Ulaanbaatar city. The
      serosurvey of adults (>20 years of age) conducted during 2013 among persons in
      four provinces and in Ulaanbaatar showed that the overall prevalence of hepatitis
      B surface antigen (HBsAg) positivity was 10.6%. The overall prevalence of anti
      hepatitis C virus (HCV) and HCV ribonucleic acid among 1,512 apparently healthy
      subjects was 15.6% (236/1,512) and 11.0% (167/1,512) respectively. In a previous
      study, we reported on the prevalence of HBV, HDV, and HCV infections in 110
      consecutive patients presenting with acute hepatitis at eight city hospitals in
      Ulaanbaatar. In that study, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were
      diagnosed as having acute hepatitis due to hepatitis A, B, C, HBV/HDV
      coinfection, and superinfection respectively. In the current study (2012-2014),
      results show that acute hepatitis A, B, C, and D was diagnosed in 47.9, 40.7,
      5.3, and 9% respectively. Chronic HBV and HCV infections, which are associated
      with cancer and cirrhosis respectively, are responsible for 95% of liver cancers
      in Mongolia. The most common etiology for hepatocellular carcinoma was HCV
      infection (n = 89, 45.6%), followed by HBV infection (n = 67, 34.4%). How to cite
      this article: Baatarkhuu O, Uugantsetseg G, Munkh-Orshikh D, Naranzul N, Badamjav
      S, Tserendagva D, Amarsanaa J, Young KD. Viral Hepatitis and Liver Diseases in
      Mongolia. Euroasian J Hepato-Gastroenterol 2017;7(1):68-72.

PMID- 29201778
TI  - Liver Disease in Sri Lanka.
AB  - Liver disease in Sri Lanka is mainly due to alcoholic liver disease and
      nonalcoholic fatty liver disease. In contrast to other South Asian countries, the
      prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A
      is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in
      people who have traveled to neighboring South Asian countries. Wilson's disease,
      autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary
      biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic
      and amebic liver abscesses and dengue infection are the other causes of liver
      disease. Some of the commonly used plants as traditional herbal medicine in Sri
      Lanka have been shown to have deleterious effects on the liver in animal studies.
      Considering the high popularity of traditional herbal medicine in the country, it
      is likely that herbal medicine is an etiological factor for liver disease in Sri
      Lanka, but no published data are available. Address reprint requests to:
      Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol
      2017;7(1):78-81.

PMID- 29201779
TI  - HBV Treatment in Turkey: The Value of Hepatitis B Surface Antigen Quantification
      of Chronic Hepatitis B Patients in the Long-term Follow-up-A Single-center Study.
AB  - Hepatitis B surface antigen (HBsAg) seems to have significant clinical
      implications to assess the prognosis of chronic hepatitis B (CHB). We assessed
      HBsAg levels serially in patients with CHB in a single center in Turkey. How to
      cite this article: Ozkan H. HBV Treatment in Turkey: The Value of Hepatitis B
      Surface Antigen Quantification of Chronic Hepatitis B Patients in the Long-term
      Follow-up-A Single-center Study. Euroasian J Hepato-Gastroenterol 2017;7(1):82
      83.

PMID- 29201780
TI  - Successful Conservative Management of Spontaneous Antegrade Migration of Feeding
      Jejunostomy.
AB  - Successful conservative management of spontaneous antegrade migration of feeding
      jejunostomy of a patient with dysphagia due to carcinoma of nasopharynx is
      reported. How to cite this article: Krishnamurthy G, Pandit N, Singh H, Singh R.
      Successful Conservative Management of Spontaneous Antegrade Migration of Feeding
      Jejunostomy. Euroasian J Hepato-Gastroenterol 2017;7(1):84-86.

PMID- 29201781
TI  - Scrotal Cystocele in a Sliding Left Inguinoscrotal Hernia: A Case Report and
      Review of Literature.
AB  - Inguinoscrotal bladder herniation has a reported incidence of 1 to 4%. Although
      small bladder herniations are noted at the time of inguinal hernia repair, large
      bladder herniation into the scrotum is rare. These patients have a unique
      presentation of signs and symptoms. We report a case of a male patient of age 64
      years who had a large inguinoscrotal hernia with bladder. He successfully
      underwent hernioplasty after repositioning of the bladder. Now, he is symptom
      free and on follow-up. How to cite this article: Mohan A, Srinivasan K. Scrotal
      Cystocele in a Sliding Left Inguinoscrotal Hernia: A Case Report and Review of
      Literature. Euroasian J Hepato-Gastroenterol 2017;7(1):87-88.

PMID- 29201782
TI  - Sclerosing Angiomatoid Nodular Transformation of the Spleen: An uncommon Cause of
      Abdominal Pain.
AB  - Sclerosing angiomatoid nodular transformation (SANT) is a rare and benign lesion
      arising from the red pulp of the spleen, with an unknown etiopathogenesis. These
      tumors are usually asymptomatic or cause nonspecific abdominal pain. Most SANTs
      are found incidentally on radiographic examination, or during surgery for an
      unrelated condition. Therefore, high clinical suspicion is of great importance
      for the diagnosis. Splenectomy provides complete cure, and no recurrence and/or
      malignant transformation was reported to date. In this study, a rare case of SANT
      was reported in a young adult male, and was discussed with the relevant
      literature. How to cite this article: Atas H, Bulus H, Akkurt G. Sclerosing
      Angiomatoid Nodular Transformation of the Spleen: An uncommon Cause of Abdominal
      Pain. Euroasian J Hepato-Gastroenterol 2017;7(1):89-91.

PMID- 29201783
TI  - Persistent Elevation of CA 19-9 Levels in the Long-term Follow-up before
      Laryngeal Cancer.
AB  - Introduction: CA 19-9 is used as a tumor marker in colon, pancreas, biliary, and
      gastric cancers. Laryngeal cancer is the most common malignant epithelial tumor
      among head and neck cancers and has no specific tumor marker. Case report: A 66
      year-old male patient had severe reflux symptoms during 5 years and had an
      isolated CA 19-9 elevation. Follow-up analysis revealed that he had larynx cancer
      and after laryngectomy, CA 19-9 levels decreased to normal range. Discussion:
      Currently, CA 19-9 is not a marker for malignancy. Laryngeal carcinoma has no
      specific tumor marker, but laryngeal squamous cell carcinoma may be manifested by
      elevated CA 19-9 levels.How to cite this article: Ozkan H, Karakaya F, Karaeren
      Z, Percinel S. Persistent Elevation of CA 19-9 Levels in the Long-term Follow-up
      before Laryngeal Cancer. Euroasian J Hepato-Gastroenterol 2017;7(1):92-94.

PMID- 29201784
TI  - Simultaneous Immunoglobulin G4-associated Autoimmune Hepatitis and Autoimmune
      Pancreatitis.
AB  - How to cite this article: Yilmaz B, Kiziltas S, Yildiz S, Gumus B, Cevik H.
      Simultaneous Immunoglobulin G4-associated Autoimmune Hepatitis and Autoimmune
      Pancreatitis. Euroasian J Hepato-Gastroenterol 2017;7(1):95-96.

PMID- 29201785
TI  - Synchronous Colon Carcinoma and Tuberculosis: Coincidence or Linked.
AB  - How to cite this article: Dayal S. Synchronous Colon Carcinoma and Tuberculosis:
      Coincidence or Linked. Euroasian J Hepato-Gastroenterol 2017;7(1):97-98.

PMID- 29201786
TI  - Long Segment Intestinal Invagination in an Adult Case.
AB  - How to cite this article: Karadeli E, Parlakgumus A, Tok S, Erbay G. Long Segment
      Intestinal Invagination in an Adult Case. Euroasian J Hepato-Gastroenterol
      2017;7(1):99-100.

PMID- 29201787
TI  - Probiotic Therapy in Patients with Nonalcoholic Steatohepatitis in Zagazig
      University Hospitals.
AB  - Aim: Nonalcoholic fatty liver disease (NAFLD) is probably the most common liver
      disorder in the world. A subgroup of NAFLD patients is characterized by injury to
      the hepatocytes and inflammation in addition to excessive fat (steatohepatitis),
      the latter condition is nominated nonalcoholic steatohepatitis (NASH). This work
      aimed to evaluate the role of probiotics on the outcome of NASH in patients
      admitted to the Tropical Medicine Department, Faculty of Medicine, Zagazig
      University (inpatients and outpatients). Materials and methods: This study was
      performed on 30 patients (17 males and 13 females), with body mass index from 30
      to 35 and average age of 44 years with bright fatty liver in ultrasonography and
      raised alanine transaminase (ALT) and aspartate transaminase (AST) and positive
      liver biopsy findings. The patients were divided into group I (case group) that
      included 15 patients who received probiotics and group II of 15 patients as
      control group who did not receive probiotics; the study was conducted between
      November 2014 and April 2016. Clinical assessment, laboratory evaluation, pelvic
      abdominal ultrasound, and liver biopsy of all cases were carried out. Results: In
      this study, there was significant decrease in liver enzymes (ALT and AST) and no
      statistically significant other laboratory findings. Also there was relief for
      dyspepsia in some patients. Conclusion: Probiotics treatment is effective, safe,
      well-tolerated, inexpensive, appropriate for long-term use, and optimally, works
      at multiple levels to downregulate inflammatory mediators, and therefore,
      probiotics could be an option in the treatment of NASH.How to cite this article:
      Monem SMA. Probiotic Therapy in Patients with Nonalcoholic Steatohepatitis in
      Zagazig University Hospitals. Euroasian J Hepato-Gastroenterol 2017;7(1):101-106.

PMID- 29201788
TI  - Prevalence of Hepatitis B Virus and Hepatitis C Virus in a Tea Garden of
      Bangladesh.
AB  - Introduction: The overall health status of workers of tea garden of Bangladesh is
      below the national standard. Also, almost nothing has been reported about status
      of hepatitis virus infection among these population and there is also a lack of
      consensus. Materials and methods: Several health-related facts, especially those
      of liver diseases, were collected from 130 workers of tea garden via
      questionnaire. Sera were also collected from these subjects to assess positivity
      of hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (anti
      HCV). Hepatitis B virus (HBV) genotype was also done using genotype-specific
      primers in HBsAg-positive sera. Results: Out of 130 tea garden workers, 5 were
      positive for HBsAg; however, none was reactive to anti-HCV. Genotyping of HBV
      deoxyribonucleic acid of 4 sera samples revealed that 2 belonged to genotype A, 1
      to genotype C, and 1 to genotype D. Various risk factors were documented in HBV
      infected subjects by analyzing the questionnaire. Conclusion: Hepatitis B virus
      in considerable high percentage is prevalent among workers of tea garden in
      Bangladesh, and immediate vaccination against HBV should be employed. Also,
      health education system should be accentuated in specific population like tea
      garden workers.How to cite this article: Al Mahtab M, Akhter S, Mollick KU, Uddin
      MH, Khan SI, Akbar SMF. Prevalence of Hepatitis B Virus and Hepatitis C Virus in
      a Tea Garden of Bangladesh. Euroasian J Hepato-Gastroenterol 2017;7(1):107-110.

PMID- 29201789
TI  - Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and
      Hepatocellular Carcinoma.
AB  - Introduction: Hepatitis B virus (HBV) infection is an established cause of
      hepatocellular carcinoma (HCC) and is associated with poor prognosis. High HBV
      deoxyribonucleic acid (DNA) load has been identified in HCC and hepatitis B
      surface antigen-positive patients. Materials and methods: This study was done in
      the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka,
      Bangladesh, from January 2006 to December 2007. Thirty patients with HBV
      infection-related HCC were enrolled. Another 30 patients with HBV-related liver
      diseases without HCC were analyzed as controls. Results: The HCC patients had a
      high viral load (>105 copies/mL), while all of the controls had low (<105
      copies/mL) viral load. Conclusion: It seems that patients with HCC bear high HBV
      DNA loads in Bangladesh, but the causes underlying this remain to be resolved.How
      to cite this article: Hussain MM, Al Mahtab M, Islam S, Ahmed N, Rahman S, Khan
      M. Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and
      Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2017;7(1):111-112.

PMID- 29201790
TI  - Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in
      a Tertiary Treatment Care Center of Bangladesh.
AB  - Introduction: Decompensated cirrhosis is associated with significantly high
      mortality resulting from hepatic failure, and liver transplantation seems to be
      the only viable indication for its management. The objective of this study is to
      assess if granulocyte colony-stimulating factor (G-CSF), a stimulatory of stem
      cell in vivo, may be of any benefit for patients with decompensated cirrhosis of
      liver. Materials and methods: Seventeen consecutive patients with decompensated
      cirrhosis of liver were recruited in this prospective study. They received
      injection of G-CSF (30 IU) over a period of 6 weeks (12 injections) in addition
      to standard of care. Results: Patients were followed up at the end of treatment
      and at 12 weeks of treatment. Treatment was well tolerated, and no significant
      adverse event was recorded in any patient. Fifteen out of 17 (88%) patients were
      alive at last follow-up. Although serum bilirubin, albumin, and prothrombin time
      improved in some patients, statistically significant improvement of Child-Pugh
      score could not be documented. Conclusion: The study establishes the safety of G
      CSF therapy in patients with decompensated cirrhosis of liver. Besides, such
      therapy may also have survival benefit, although long-term follow-up is needed to
      assess its real utility in clinical perspectives.How to cite this article: Al
      Mahtab M, Alam SMN, Moben AL, Raihan R, Alam MA, Rahim MA, Uddin MH, Akbar SMF.
      Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in
      a Tertiary Treatment Care Center of Bangladesh. Euroasian J Hepato-Gastroenterol
      2017;7(1):113-115.

PMID- 29201791
TI  - Psychological Results of 438 Patients with persisting Gastroesophageal Reflux
      Disease Symptoms by Symptom Checklist 90-Revised Questionnaire.
AB  - Aims and objectives: Gastroesophageal reflux disease (GERD) affects mental state
      and social activities. On the contrary, mental disorders may also play a crucial
      role in GERD symptoms. The purpose of the study was to analyze the data of
      Symptom Checklist 90-Revised (SCL-90-R) questionnaire from patients with
      persisting GERD and to explore the impact of psychological factors on them.
      Materials and methods: The patients accepted SCL-90-R questionnaire survey,
      following endoscopy, high-resolution manometry (HRM), and ambulatory impedance-pH
      monitoring. Based on these results, we divided patients into different groups.
      The result of SCL-90-R was also compared with degree of acid reflux, symptoms,
      symptom duration, and gender. Results: The data from 438 patients were analyzed.
      All patients were divided into reflux esophagitis (RE; 63, 14.38%); nonerosive
      gastroesophageal reflux disease (NERD; 106, 24.20%); functional heartburn (FH;
      123, 28.08%), hypersensitive esophagus (HE; 67, 15.29%), diffuse esophageal spasm
      (DES; 5: 1.14%), hypertensive (10, 3.42%); weak peristalsis (14, 3.20%);
      achalasia (50, 11.42%). There were significant differences between different
      groups regarding depression (DEP), anxiety (ANX), paranoid ideation (PAR), and
      psychoticism (PSY). The patients with >=2 years with GERD presented with
      increased scores in DEP, ANX, and PSY. Women had dramatically higher scores than
      men in each domain (p < 0.05). Conclusion: Data have shown that GERD patients
      exhibit differential levels of psychological symptoms. Long duration of GERD was
      related to typical plus atypical symptoms and females seem to be more prone to
      develop psychological disorders.How to cite this article: Chen X, Li P, Wang F,
      Ji G, Miao L, You S. Psychological Results of 438 Patients with persisting
      Gastroesophageal Reflux Disease Symptoms by Symptom Checklist 90-Revised
      Questionnaire. Euroasian J Hepato-Gastroenterol 2017;7(2):117-121.

PMID- 29201792
TI  - Does Chicago Classification address Symptom Correlation with High-resolution
      Esophageal Manometry?
AB  - Aim: To assess the correlation of symptoms with findings on esophageal high
      resolution manometry (HRM) in Indian patients. Materials and methods: Prospective
      data collection of all patients undergoing esophageal manometry was done at two
      centers in India-Indore and Chennai-over a period of 18 months. Symptom profile
      of the study group was divided into four: Motor dysphagia, noncardiac chest pain
      (NCCP), gastroesophageal reflux (GER), and esophageal belchers. The symptoms were
      correlated with manometric findings. Results: Of the study group (154), 35.71%
      patients had a normal study, while major and minor peristaltic disorders were
      noted in 31.16 and 33.76% respectively. In patients with symptoms of dysphagia,
      achalasia cardia was the commonest cause (45.1%), followed by ineffective
      esophageal motility (IEM) (22.53%) and normal study (19.71%). In patients with
      NCCP, normal peristalsis (50%) and ineffective motility (31.25%) formed the major
      diagnosis. Of the 56 patients with GER symptoms, 26 (46.4%) had normal manometry.
      An equal number had ineffective motility. Of the 11 esophageal belchers, 7
      (63.6%) of these had a normal study and 3 had major motility disorder. Dysphagia
      was the only symptom to have a high likelihood ratio and positive predictive
      value to pick up major motility disorder. Conclusion: Dysphagia correlates with
      high chance to pick up a major peristaltic abnormality in motor dysphagia. The
      role of manometry in other symptoms in Indian setting needs to be ascertained by
      larger studies. Clinical significance: The present study highlights lack of
      symptom correlation with manometry findings in Indian patients.How to cite this
      article: Jain M, Srinivas M, Bawane P, Venkataraman J. Does Chicago
      Classification address Symptom Correlation with High-resolution Esophageal
      Manometry? Euroasian J Hepato-Gastroenterol 2017;7(2):122-125.

PMID- 29201793
TI  - Intrahepatic Cholestasis of Pregnancy: Spontaneous vs in vitro Fertilization.
AB  - Aim: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease
      in pregnancy. Although it was shown that multiple pregnancy and hormone therapies
      increase the risk of ICP, there is limited information that compared spontaneous
      fertilization and in vitro fertilization (IVF) from the aspect of developing ICP.
      In our study, we investigated the potential relationship between ICP and IVF/
      spontaneous pregnancy. Materials and methods: We reviewed the records (between
      June 2007 and December 2014) of pregnancies with ICP who were referred to
      gastroenterology clinics in three different hospitals. Fifty-nine pregnancies (43
      spontaneous fertilization, 16 IVF) with ICP were analyzed from the aspect of age,
      fertilization type, multiple/singleton pregnancy, delivery week, and biochemical
      results. Results: We found that serum bile acid levels were higher in the IVF
      group than the spontaneous fertilization group (32.8 +/- 20 vs 19.6 +/- 19
      MUmol/L; p < 0.05). There was a significant inverse correlation between serum
      bile acid levels and gestational age (r = -0.42, p < 0.01) in the whole group.
      There was no difference between IVF and spontaneous fertilization groups in term
      of age, onset time of symptoms, serum alanine aminotransferase (ALT), alkaline
      phosphatase (ALP), total and direct bilirubin levels, prothrombin time (PT),
      international normalized ratio (INR), and platelet count. Conclusion: Our results
      suggest that the serum bile acid levels are higher in IVF than in spontaneous
      pregnancies with ICP, but its clinical implications are not clear. Further
      prospective studies with large number of ICP cases are needed to clarify the
      effect of IVF on ICP.How to cite this article: Bolukbas FF, Bolukbas C, Balaban
      HY, Aygun C, Ignak S, Ergul E, Yazicioglu M, Ersahin SS. Intrahepatic Cholestasis
      of Pregnancy: Spontaneous vs in vitro Fertilization. Euroasian J Hepato
      Gastroenterol 2017;7(2):126-129.

PMID- 29201794
TI  - Role of Probiotics in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta
      analysis.
AB  - Aim: Despite extensive ongoing research, there is scarcity of widely accepted
      therapeutic options for the treatment of nonalcoholic fatty liver disease
      (NAFLD). Probiotics are a promising treatment option for treating NAFLD; however,
      their effectiveness needs to be established. Since any single randomized
      controlled trial (RCT) cannot establish the role of probiotics in the treatment
      of NAFLD, this study aims at meta-analysis of different RCTs. Materials and
      methods: Extensive search was done by two independent observers for RCTs studying
      the role of probiotics in the treatment of NAFLD. The parameters under
      consideration were body mass index (BMI), aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), homeostatic model assessment of insulin
      resistance (HOMA-IR), serum triglycerides (TGs), and ultrasonographic grades of
      fatty liver. Jadad scale was used to select the articles for meta-analysis.
      Heterogeneity in the results was evaluated using chi-square test and I2.
      Significant heterogeneity in the results was decided based on p-value < 0.05 and
      the corresponding I2 close to 0%. Results: Seven studies qualified for meta
      analysis. Use of probiotics significantly caused reduction in BMI (p < 0.0001),
      ALT (p < 0.0001), AST (< 0.0001), HOMA-IR (p = 0.006), and ultrasonographic grade
      of fatty liver (p = 0.0051). Heterogeneity in other parameters was contributed
      mainly by couple of previous studies. Conclusion: Meta-analysis shows that
      variety of parameters has significant improvement after probiotic treatment in
      different RCTs. However, the magnitude of improvement is not uniform across
      studies due to varying strains, dose patterns, and treatment duration. In future,
      probiotics remain a promising option for treating NAFLD.How to cite this article:
      Lavekar AS, Raje DV, Manohar T, Lavekar AA. Role of Probiotics in the Treatment
      of Nonalcoholic Fatty Liver Disease: A Meta-analysis. Euroasian J Hepato
      Gastroenterol 2017;7(2):130-137.

PMID- 29201795
TI  - Pneumatic Balloon Dilatation for Achalasia Cardia: Outcome, Complications,
      Success, and Long-term Follow-up.
AB  - Background: Achalasia is a chronic disease that can be managed with effective
      endoscopic modalities. Aim: To evaluate the effectiveness of single setting of
      pneumatic balloon dilatation for achalasia and assess the long-term success and
      outcomes. Materials and methods: This is a retrospective study of all achalasia
      patients who underwent pneumatic balloon dilatation at our institute. Patients
      who could be contacted were inquired regarding their symptoms and dysphagia-free
      interval after dilatation. Results: A total of 72 patients were enrolled. Out of
      this, 14 patients lost to follow-up. Mean age of 58 patients was 45.02 +/- 16.51
      years. Male:female ratio was 13:16. Mean predilatation Eckardt score was 7.16 +/-
      0.834. Type I achalasia was present in 10 (17.2%), type II in 44 (75.9%), type
      III in 4 (6.9%). Predilatation basal integrated relaxation pressure (IRP) was
      28.14 +/- 14.76 mm Hg. Postdilatation Eckardt score was 2.40 +/- 1.67.
      Postdilatation dysphagia-free interval was 17.28 +/- 6.70 months. A total of 9
      patients (15.51%) failed to respond to first dilatation and 49 (84.48%) patients
      benefited from single setting of pneumatic dilatation. Esophageal perforation
      occurred in 2/58 (3.44%). We did not find any significant difference in gender
      distribution, age of presentation, duration of symptom, pre- and postdilatation
      Eckardt score, type of achalasia, and basal IRP on manometry between type of
      achalasia. Postdilatation dysphagia-free interval in type II achalasia (18.09 +/-
      5.976 months) was more than types I and III achalasia cardia (p = 0.066), which
      showed trend toward significance. Conclusion: Pneumatic balloon dilatation of
      achalasia cardia is a highly effective endoscopic procedure with minimal
      complications and mortality. Even the single setting of dilatation can have long
      lasting dysphagia-free interval.How to cite this article: Gupta SJ, Gaikwad NR,
      Samarth AR, Gattewar SR. Pneumatic Balloon Dilatation for Achalasia Cardia:
      Outcome, Complications, Success, and Long-term Follow-up. Euroasian J Hepato
      Gastroenterol 2017;7(2):138-141.

PMID- 29201796
TI  - Hepatic Venous Pressure Gradient Measurement in Bangladeshi Cirrhotic Patients: A
      Correlation with Child's Status, Variceal Size, and Bleeding.
AB  - Background: Hepatic venous pressure gradient (HVPG) reflects the portal pressure
      in patients with cirrhotic portal hypertension. The aim of the study was to
      assess the relation of HVPG to variceal size, Child-Pugh status, and variceal
      bleeding. Materials and methods: A total of 96 patients with cirrhosis of liver
      were enrolled prospectively and each patient's HVPG level was measured via the
      transfemoral route. Clinical and biochemical evaluation and upper
      gastrointestinal (GI) endoscopy were done in each subject. Severity of cirrhosis
      was assessed by Child's status. Results: The mean HVPG was higher in patients
      with Child's B and C (14.10 +/- 7.56 and 13.64 +/- 7.17 mm Hg respectively)
      compared with those of Child's A (10.15 +/- 5.63 mm Hg). The levels of HVPG
      differed significantly between Child's classes A and B (p = 0.011) and Child's A
      and C (p = 0.041). The mean HVPG was also higher in bleeders compared with
      nonbleeders with large varices (17.7 +/- 5.5 vs 14.9 +/- 4.7 mmHg respectively; p
      = 0.006). Conclusion: Hepatic venous pressure gradient seems to be important to
      assess the severity of liver cirrhosis.How to cite this article: Al Mahtab M,
      Noor E Alam SM, Rahim MA, Alam MA, Khondaker FA, Moben AL, Mohsena M, Akbar SMF.
      Hepatic Venous Pressure Gradient Measurement in Bangladeshi Cirrhotic Patients: A
      Correlation with Child's Status, Variceal Size, and Bleeding. Euroasian J Hepato
      Gastroenterol 2017;7(2):142-145.

PMID- 29201797
TI  - Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy Premedication.
AB  - Aim: Percutaneous needle liver biopsy (PLB) is frequently associated with pain
      and anxiety. This may discourage the patients for biopsy, and rebiopsies, if
      needed. We planned a study to investigate the efficacy of additional analgesia or
      sedation for PLB. Materials and methods: The study has been designed as a single
      center, prospective study. The PLB was planned for 18- to 65-year-old consecutive
      patients who were included in the study. The patients were divided into three
      premedication groups as control, Meperidine, and Midazolam. Hospital Anxiety and
      Depression Scale (HADS) was used to measure each subject's anxiety level. Fifteen
      minutes before the biopsy, 1 mL 0.9% NaCl subcutaneously (sc), 1 mg/kg (max 100
      mg) Meperidine sc, or 0.1 mg/kg (max 5 mg) Midazolam intravenously was
      administered to patients respectively. Then PLB was done with 16 G Menghini
      needle. The day after, the patients were asked about feelings regarding biopsy.
      Results: Groups were similar by gender and age. The HADS scores prior to PLB and
      on visual analog scale (VAS, 1-10 points) score during PLB were similar. In the
      three groups, 7, 12, and 7 patients, respectively, experienced no pain. Other
      patients explained pain as mild or moderate or severe. The number of patients who
      agreed for possible rebiopsy was higher in Meperidine and Midazolam groups than
      in the control group. Conclusion: Premedication with Meperidine or Midazolam in
      PLB would improve patients' tolerance, comfort, and attitude against a possible
      repeat PLB.How to cite this article: Sezgin O, Yaras S, Ates F, Altintas E,
      Saritas B. Effectiveness of Sedoanalgesia in Percutaneous Liver Biopsy
      Premedication. Euroasian J Hepato-Gastroenterol 2017;7(2):146-149.

PMID- 29201798
TI  - Adrenal Insufficiency in Cirrhosis Patients: Evaluation of 108 Case Series.
AB  - Aim: Adrenal insufficiency (AI) in cirrhosis is an issue that has recently gained
      momentum. It can be seen in both stable and critically ill (sepsis, septic shock,
      and gastrointestinal system bleeding) cirrhotic patients. Its prevalence exists
      in a wide range since standardization of diagnostic methods is lacking. We aimed
      to scrutinize this issue in a 108 case series. Materials and methods: We studied
      the presence of AI and its stage in patients with cirrhosis and its complications
      by using cross-sectional study. Standard-dose short synacthen test (SD-SST) was
      performed in 108 patients that had Child C decompensated cirrhosis without
      critical illness and it was aimed to determine the prevalence of AI based on
      basal cortisol, peak cortisol, and delta cortisol (basal total cortisol minus
      peak cortisol after stimulation) levels. Results: The prevalence of AI in
      cirrhosis was found to be 25% based on basal cortisol level of <140 nmol/L, 22.2%
      based on delta cortisol level of <250 nmol/L, and 29.6% based on peak cortisol
      level of <500 nmol/L. Conclusion: Prevalence of AI shows variation in
      decompensated cirrhosis without critical illness depending on different measures
      used. More definite results can be obtained when more standardized criteria are
      widely put into use.How to cite this article: Rakici H. Adrenal Insufficiency in
      Cirrhosis Patients: Evaluation of 108 Case Series. Euroasian J Hepato
      Gastroenterol 2017;7(2):150-153.

PMID- 29201799
TI  - Hemochromatosis Gene Polymorphism as a Predictor of Sustained Virological
      Response to Antiviral Treatment in Egyptian Chronic Hepatitis C Patients.
AB  - Aim: The aim of this article is to assess HFE C282Y gene mutations as a predictor
      of sustained virological response (SVR) to anti-hepatitis C virus (HCV) treatment
      in Egyptian patients. Materials and methods: One hundred and forty chronic
      hepatitis C (CHC) patients were divided into two groups: 70 patients achieved SVR
      and 70 patients were nonresponders (NRs). All patients were subjected to
      quantitative polymerase chain reaction (PCR) at baseline, 12 and 24 weeks after
      therapy commencement. Deoxyribonucleic acid (DNA) sequencing for HFE (C282Y) was
      done by restriction fragment length polymorphism PCR. Results: Sixty five
      patients did not have mutation and 5 patients had C282Y mutation (GA) with SVR.
      While 45 NRs had heterozygous C282Y mutation (GA), 4 patients (5.7%) had
      homozygous mutation (AA) and 21 patients (30%) had no mutation (GG). The
      parameters of elevated iron [transferrin saturation (TS; p < 0.001), S iron (p <
      0.02), total iron binding capacity (TIBC; p < 0.001), transferrin (p < 0.016),
      and soluble transferrin receptor (sTfR; p-value, 0.001)] were significantly
      associated with C282Y mutation. However, there was no significant difference
      regarding ferritin values and C282Y mutation in NR patients. Conclusion: Iron
      overload was frequently detected in CHC patients and associated with C282Y
      mutation, while biochemical markers of iron overload and C282Y HFE mutation were
      negative prognostic factor.How to cite this article: Mehrez MI, Fattah DSA, Azeem
      NAA, Saleh MA, Mostafa KM. Hemochromatosis Gene Polymorphism as a Predictor of
      Sustained Virological Response to Antiviral Treatment in Egyptian Chronic
      Hepatitis C Patients. Euroasian J Hepato-Gastroenterol 2017;7(2):154-157.

PMID- 29201800
TI  - Effect of Different Sedation Regimes on Cognitive Functions in Colonoscopy.
AB  - Aim: To compare the effects of propofol/remifentanil and meperidine/midazolam on
      postprocedure cognitive function. Materials and methods: A total of 100 American
      Society of Anesthesiologists (ASA) score I to III patients undergoing elective
      colonoscopy were taken into the study and divided into two groups. Exclusion
      criteria were patient refusal, mini mental test (MMT) <26, The Amsterdam
      Preoperative Anxiety and Information Scale (APAIS) >10, advanced cardiopulmonary
      or psychiatric disease, chronic alcohol abuse, morbid obesity, and known allergy
      to study drugs. In group MM, 2 mg midazolam and 20 mg meperidine was given
      intravenously and additional 1 to 2 mg midazolam and 20 mg meperidine (with a
      maximum total of 5 mg midazolam and 50 mg meperidine) was given when bispectral
      index (BIS) was >80. In group RP, 100 MUg/kg/minute propofol infusion and 1
      MUg/kg remifentanil bolus was administered and additional 0.5 MUg/kg remifentanil
      bolus was given when BIS was >80. Observer's Assessment of Alertness/Sedation
      scale (OAA/S) and Facial Pain Score (FPS) values were recorded. Cognitive
      function was measured by Trieger Dot Test (TDT) and Digit Symbol Substitution
      Test (DSST). Results: The study was concluded with 100 patients. Heart rate was
      slower and BIS values were lower in group RP throughout the procedure. Blood
      pressure was lower in group RP without clinical significance. There was no
      difference concerning recovery time and visual analog scores (VASs). In group MM,
      TDT scores were higher and DSST scores were lower. Satisfaction was higher in
      group RP. Conclusion: Propofol/remifentanil combination is better than
      meperidine/midazolam combination concerning cognitive function in sedation for
      colonoscopy. Clinical significance: The addition of BIS monitorization to
      evaluate the depth of sedation and the negative effects of midazolam meperidine
      combination on postprocedural cognitive function.How to cite this article:
      Ekmekci P, Erkan G, Yilmaz H, Kazbek BK, Koksoy UC, Doganay G, Tuzuner F. Effect
      of Different Sedation Regimes on Cognitive Functions in Colonoscopy. Euroasian J
      Hepato-Gastroenterol 2017;7(2):158-162.

PMID- 29201801
TI  - Viral Hepatitis in South Korea.
AB  - In South Korea (S. Korea), viral hepatitis is a major public health burden.
      Advances in healthcare policy, evidence-based medicine, and therapeutic
      strategies in S. Korea have brought a rapid change in the sociodemographic and
      clinical characteristics of viral hepatitis. This review discusses the innovative
      approaches that S. Korea has taken to curb the epidemic of viral hepatitis. In
      addition, the efficacy of various preventive and therapeutic modalities is
      discussed. This review aims to provide a brief overview to guide future research
      direction and healthcare policy changes. How to cite this article: Pak SC,
      Alastal Y, Khan Z, Darr U. Viral Hepatitis in South Korea. Euroasian J Hepato
      Gastroenterol 2017;7(2):163-165.

PMID- 29201803
TI  - Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative
      Management.
AB  - Typhoid fever is caused by gram-negative organism Salmonella typhi. The usual
      presentation is high-grade fever, but complications like gastrointestinal (GI)
      hemorrhage and perforation are also seen frequently. With the advent of
      antibiotics, these complications are rarely seen now. We present a case of a
      young female who was admitted with a diagnosis of typhoid fever presented with a
      massive GI bleed from ulcers in the terminal ileum and was managed conservatively
      without endotherapy and surgery. How to cite this article: Goel A, Bansal R.
      Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative
      Management. Euroasian J Hepato-Gastroenterol 2017;7(2):176-177.

PMID- 29201802
TI  - Hepatic Metastasis from Colorectal Cancer.
AB  - The liver is the most common site of metastasis in patients with colorectal
      cancer due to its anatomical situation regarding its portal circulation. About 14
      to 18% of patients with colorectal cancer present metastasis at the first medical
      consultation, and 10 to 25% at the time of the resection of the primary
      colorectal cancer. The incidence is higher (35%) when a computed tomography (CT)
      scan is used. In the last decades, a significant increase in the life expectancy
      of patients with colorectal cancer has been achieved with different diagnostic
      and treatment programs. Despite these improvements, the presence of metastasis,
      disease recurrence, and advanced local tumors continue to remain poor prognostic
      factors. Median survival without treatment is <8 months from the moment of its
      presentation, and a survival rate at 5 years of 11% is the best prognosis for
      those who present with local metastasis. Even in patients with limited metastatic
      disease, 5-year survival is exceptional. Patients with hepatic metastasis of
      colorectal cancer have a median survival of 5 to 20 months with no treatment.
      Approximately 20 to 30% of patients with colorectal metastasis have disease
      confined to the liver, and this can be managed with surgery. Modern surgical
      strategies at the main hepatobiliary centers have proved that hepatectomy of 70%
      of the liver can be performed, with a mortality rate of <5%. It is very important
      to have knowledge of predisposing factors, diagnostic methods, and treatment of
      hepatic metastasis. However, the establishment of newer, efficient, preventive
      screening programs for early diagnosis and adequate treatment is vital. How to
      cite this article: Valderrama-Trevino AI, Barrera-Mera B, Ceballos-Villalva JC,
      Montalvo-Jave EE. Hepatic Metastasis from Colorectal Cancer. Euroasian J Hepato
      Gastroenterol 2017;7(2):166-175.

PMID- 29201804
TI  - Aneurysm of Portosystemic Fistula: A Case Report and Review of Literature.
AB  - Aim: A case of asymptomatic aneurysm of spontaneous portosystemic venous fistula
      (SPVF) with the radiologic findings is described. Background: Although advances
      and more widespread use of ultrasound (US) and computed tomog -raphy angiography
      (CTA) have enabled more detection of SPVF in the liver, it is a rare entity. Case
      report: A 49-year-old male was referred to our hospital's nephrology outpatient
      clinic due to hypertension. Abdominal sonography examination detected a well
      defined cystic lesion adjacent to the middle hepatic vein in the liver. The
      lesion showed venous flow in the color Doppler US examination. Computed
      tomography angiography examination revealed an aneurysm of the fistula.
      Conclusion: Radiologists should be aware of this vascular anomaly and cyst-like
      lesions in the liver should be examined with color Doppler ultrasonography for
      possible vascularization, and be differentiated with CTA if necessary. Clinical
      significance: This condition is usually encountered incidentally and patients
      usually have no symptoms. However, severe complications, such as hepatopulmonary
      syndrome, liver tumors, encephalopathy, and heart failure can be seen.How to cite
      this article: Ulus S, Akan GE, Erol C. Aneurysm of Portosystemic Fistula: A Case
      Report and Review of Literature. Euroasian J Hepato-Gastroenterol 2017;7(2):178
      180.

PMID- 29201805
TI  - Porcelain Gallbladder.
AB  - Porcelain gallbladder or calcified gallbladder is a rare entity and is considered
      as the end stage of chronic cholecystitis. This disease is rarely diagnosed
      preoperatively and usually mimics carcinoma gallbladder. Hereby, we present a
      rare and interesting case of porcelain gallbladder that was diagnosed
      preoperatively and managed by cholecystectomy. How to cite this article: Goel A,
      Agarwal A, Gupta S, Bhagat TS, Kumar G, Gupta AK. Porcelain Gallbladder.
      Euroasian J Hepato-Gastroenterol 2017;7(2):181-182.

PMID- 29201806
TI  - A Rare Case of Complete Agenesis of Dorsal Pancreas.
AB  - Agenesis of dorsal pancreas (ADP) is an extremely rare congenital anomaly that
      results from defective development of pancreas. Most ADP patients are
      asymptomatic; if symptomatic, they present with epigastric pain. About half of
      affected individuals develop diabetes mellitus (DM), resulting from reduced islet
      cell mass secondary to the absence of endocrine structures. Being very rare, it
      is generally not kept in mind while dealing these cases and are not suspected
      until imaging investigations are not done. In our case study, ADP was diagnosed
      during evaluation of the patient for recurrent pain abdomen and generalized
      weakness. How to cite this article: Jain A, Singh M, Dey S, Kaura A, Diwakar G. A
      Rare Case of Complete Agenesis of Dorsal Pancreas. Euroasian J Hepato
      Gastroenterol 2017;7(2):183-184.

PMID- 29201807
TI  - Ascitic Fluid/Serum Bilirubin Ratio as an aid in Preoperative Diagnosis of
      Choleperitoneum in a Neglected Case of Spontaneous Common Bile Duct Perforation.
AB  - Spontaneous perforation of extrahepatic biliary system is a rare and potentially
      fatal cause of acute abdomen. Clinical presentation is as biliary peritonitis.
      This condition is rarely suspected as a cause of peritonitis preoperatively and
      correct diagnosis is made during surgery. If suspected, diagnosis can be made by
      various imaging techniques like hepatobiliary scintigraphy, magnetic resonance
      cholangiopancreatography (MRCP), and endoscopic retrograde
      cholangiopancreatography (ERCP). As these imaging techniques are not readily
      available, especially in low socioeconomic countries, we hereby report a case of
      spontaneous common bile duct (CBD) perforation, which was diagnosed
      preoperatively by estimation of ascitic fluid-to-serum bilirubin ratio, a simple,
      quick, and cost-effective test. How to cite this article: Huda F, Naithani M,
      Singh SK, Saha S. Ascitic Fluid/Serum Bilirubin Ratio as an aid in Preoperative
      Diagnosis of Choleperitoneum in a Neglected Case of Spontaneous Common Bile Duct
      Perforation. Euroasian J Hepato-Gastroenterol 2017;7(2):185-187.

PMID- 29201808
TI  - Management of Traumatic Liver and Bile Duct Laceration.
AB  - Posttraumatic major bile leak in children is uncommon, with few cases reported in
      the literature. These injuries are seen in high-grade liver trauma and are
      difficult to diagnose and manage. We describe a 7-year-old boy with grade IV
      hepatic trauma and bile leak following blunt abdominal trauma. The leak was
      successfully managed by percutaneous drainage and endoscopic retrograde
      cholangiopancreatography (ERCP) stenting of the injured hepatic duct. How to cite
      this article: Tiwari C, Shah H, Waghmare M, Khedkar K, Dwivedi P. Management of
      Traumatic Liver and Bile Duct Laceration. Euroasian J Hepato-Gastroenterol
      2017;7(2):188-190.

PMID- 29201809
TI  - Long Esophageal Stricture in a Brittle Diabetic.
AB  - Aim: We report a case of atypical esophageal stricture in a young diabetic woman.
      Background: Diabetes mellitus and gastroesophageal reflux disease (GERD) are two
      common disorders in modern society. Case report: A young diabetic woman developed
      a 6-cm-long esophageal stricture. This stricture was refractory to multiple
      esophageal dilation procedures. She underwent subtotal esophagectomy and had
      excellent treatment outcome. Conclusion: Gastroesophageal reflux disease can
      cause severe long esophageal stricture in a brittle diabetic. Clinical
      significance: Improving the awareness of their association between diabetes and
      GERD would greatly benefit the day-to-day practice of medicine.How to cite this
      article: Pak SC, Darr U, Alastal Y, Yoon Y. Long Esophageal Stricture in a
      Brittle Diabetic. Euroasian J Hepato-Gastroenterol 2017;7(2):191-192.

PMID- 29201810
TI  - Subcortical Aphasia After Stroke.
AB  - Objective: To evaluate the types and severity of subcortical aphasia after stroke
      and to determine the predictors of the degree of aphasic impairment. Methods:
      Medical records of 38 patients with post-stroke subcortical aphasia (19 males;
      mean age, 61.7+/-13.8 years) were reviewed retrospectively with respect to the
      following tests: the Korean version of the Western Aphasia Battery (K-WAB), the
      Korean version of the Modified Barthel Index (K-MBI), and the Fugl-Meyer Index
      (FMI). The severity of aphasia was evaluated by the aphasia quotient (AQ) and the
      language quotient (LQ). Results: Anomic aphasia was the most frequent type of
      aphasia (n=15, 39.5%), and the lesion most frequently observed in subcortical
      aphasia was located in the basal ganglia (n=19, 50.0%). Patients with lesions in
      the basal ganglia exhibited the lowest scores on the FMI for the upper
      extremities (p=0.04). Severity of aphasia was significantly correlated with the K
      MBI (Pearson correlation coefficient: gamma=0.45, p=0.01 for AQ and gamma=0.53,
      p=0.01 for LQ) and FMI scores for the lower extremities (gamma=0.43, p=0.03 for
      AQ and gamma=0.49, p=0.05 for LQ). In a multivariate logistic regression
      analysis, K-MBI remained the only explanatory variable closely associated with
      aphasia severity. Conclusion: This study showed the general characteristics of
      post-stroke subcortical aphasia, and it revealed that K-MBI was an associated and
      explanatory factor for aphasia severity.

PMID- 29201811
TI  - The Characteristics of Cognitive Impairment and Their Effects on Functional
      Outcome After Inpatient Rehabilitation in Subacute Stroke Patients.
AB  - Objective: To determine the frequency and characteristics of vascular cognitive
      impairment (VCI) in patients with subacute stroke who underwent inpatient
      rehabilitation and to analyze whether cognitive function can predict functional
      assessments after rehabilitation. Methods: We retrospectively reviewed the
      medical records of patients who were admitted to our rehabilitation center after
      experiencing a stroke between October 2014 and September 2015. We analyzed the
      data from 104 patients who completed neuropsychological assessments within 3
      months after onset of a stroke. Results: Cognitive impairment was present in 86
      out of 104 patients (82.6%). The most common impairment was in visuospatial
      function (65, 62.5%) followed by executive function (63, 60.5%), memory (62,
      59.6%), and language function (34, 32.6%). Patients with impairment in the
      visuospatial and executive domains had poor scores of functional assessments at
      both admission and discharge (p<0.05). A multivariate analysis revealed that age
      (beta=-0.173) and the scores on the modified Rankin Scale (beta=-0.178), Korean
      version of the Modified Barthel Index (K-MBI) (beta=0.489) at admission, and
      Trail-Making Test A (TMT-A) (beta=0.228) were related to the final K-MBI score at
      discharge (adjusted R2=0.646). Conclusion: In our study, VCI was highly prevalent
      in patients with stroke. TMT-A scores were highly predictive of their final K-MBI
      score. Collectively, our results suggest that post-stroke executive dysfunction
      is a significant and independent predictor of functional outcome.

PMID- 29201812
TI  - The Factors Associated With Health-Related Quality of Life in Stroke Survivors
      Age 40 and Older.
AB  - Objective: To evaluate the association between clinical and socio-demographic
      status and health-related quality of life (HR-QoL) in stroke survivors age 40 and
      older in the Korean population. Methods: The relationship between stroke and HR
      QoL was investigated using data from the Korea National Health and Nutrition
      Examination Survey (KNHANES), conducted from 2007-2012. The total number of
      respondents was 24,050 and 757 stroke survivors were included. Specifically, we
      investigated factors associated with the lowering of HR-QoL in a group of Korean
      adult stroke patients age 40 and older after adjusting for socio-demographic
      factors, anthropometric measurements, and clinical comorbidities. Adjusted
      effects of covariates on EuroQol-visual analog scales (EQ-VAS) scores were
      estimated with a complex-samples general linear model and multivariate-adjusted
      odds ratios of the lowest quintile versus highest quintile of the EQ-VAS scores
      in the stroke group were estimated with a complex-samples logistic regression
      model. Results: Socio-demographic, anthropometric factors, and clinical
      comorbidities significantly differed between the stroke and non-stroke groups,
      except regarding gender and residential area. The EQ-VAS was significantly lower
      in the stroke than non-stroke group. Anxiety/depression problems significantly
      lowered EQ-VAS, as did low education level, smoking, mobility and usual
      activities problems. Also, aging in 1-year increments and cardiovascular disease
      had a significant effect on lower EQ-VAS in stroke survivors. Conclusion: People
      with a stroke have significantly lower HR-QoL than healthy subjects. Therefore,
      managing depression, smoking, or cardiovascular disease and maintenance of
      physical function may be priority goals in improving HR-QoL after a stroke.

PMID- 29201813
TI  - Risk Factors and Functional Impact of Medical Complications in Stroke.
AB  - Objective: To determine the incidence and risk factors for medical complications
      in Korean patients suffering from stroke and the impact of such complications on
      post-stroke functional outcomes. Methods: We assessed patients enrolled in a
      prospective cohort study. All recruited patients had suffered a first acute
      stroke episode and been admitted to nine university hospitals in Korea between
      August 2012 and June 2015. We analyzed patient and stroke characteristics,
      comorbidities, prevalence of post-stroke medical complications, and functional
      outcomes at time of discharge and 3, 6, and 12 months after stroke onset.
      Results: Of 10,625 patients with acute stroke, 2,210 (20.8%) presented with
      medical complications including bladder dysfunction, bowel dysfunction, sleep
      disturbance, pneumonia, and urinary tract infection. In particular, complications
      occurred more frequently in older patients and in patients with hemorrhagic
      strokes, more co-morbidities, severe initial motor impairment, or poor swallowing
      function. In-hospital medical complications were significantly correlated with
      poor functional outcomes at all time points. Conclusion: Post-stroke medical
      complications affect functional recovery. The majority of complications are
      preventable and treatable; therefore, the functional outcomes of patients with
      stroke can be improved by providing timely, appropriate care. Special care should
      be provided to elderly patients with comorbid risk factors.

PMID- 29201814
TI  - Life Space Assessment in Stroke Patients.
AB  - Objective: To evaluate the reliability of the practical life space in post-stroke
      patients using the Korean version of the Life-Space Assessment (K-LSA)
      questionnaire and to assess the relationships between the K-LSA and physical
      function, daily activity, quality of life, and post-stroke depression. Methods:
      The LSA questionnaire was translated into Korean, and the translated version was
      authorized by the author of the LSA questionnaire. In a cross-sectional study,
      the performance of the K-LSA was evaluated in 34 stroke patients (20 males and 14
      females; mean age 65.11+/-2.39 years) who were receiving physical and
      occupational therapy at the outpatient clinic in the rehabilitation medicine
      department of a university medical center at the time of evaluation. Performances
      were assessed twice by one examiner at a 2-week interval to test the reliability.
      The patients were evaluated using the Functional Ambulation Category (FAC) scale,
      Functional Independence Measure (FIM) scale, and mobility subscale of the FIM to
      assess their relationships with the K-LSA. They were also evaluated using the
      EuroQol 5 Dimensions questionnaire (EQ-5D) and Geriatric Depression Scale (GDS)
      to determine the relationship with quality of life and post-stroke depression.
      Results: Test-retest reliability at the first (62.20+/-32.14) and second (63.15+/
      32.22) assessment was 0.993 (p<0.01). The K-LSA showed significant correlations
      with the FAC (r=0.848, p<0.01), FIM (r=0.765, p<0.01), mobility category of the
      FIM (r=0.764, p<0.01), GDS (r=-0.657, p<0.01), and EQ-5D (r=0.506, p<0.01).
      Conclusion: This study suggests that the practical life space of post-stroke
      patients, assessed by the K-LSA, has a significant correlation with patients'
      functional mobility, independence in daily activity, quality of life, and
      depression.

PMID- 29201815
TI  - Clinical Predictors of Oro-esophageal Tube Feeding Success in Brain Injury
      Patients With Dysphagia.
AB  - Objective: To identify possible clinical predictors of intermittent oro
      esophageal (OE) tube feeding success, and evaluate the clinical factors
      associated with OE tube treatment. Methods: A total of 135 dysphagic patients
      were reviewed, who received OE tube treatment and were hospitalized in the
      department of rehabilitation medicine between January 2005 and December 2014. The
      76 eligible cases enrolled were divided into two groups, based on the OE tube
      training success. Clinical factors assessed included age, cause of brain lesion,
      gag reflex, cognitive function and reasons for OE tube training failure. Results:
      Of the 76 cases enrolled, 56 study patients were assigned to the success group,
      with the remaining 20 in the failure group. There were significant differences
      between these two groups in terms of age, gag reflex, ability to follow commands,
      and the score of Korean version of Mini-Mental Status Examination (K-MMSE).
      Location of the brain lesion showed a borderline significance. Multivariable
      analysis using logistic regression revealed that age, cause of brain lesion, gag
      reflex, and K-MMSE were the main predictors of OE tube training success.
      Conclusion: A younger age, impaired gag reflex and higher cognitive function
      (specifically a K-MMSE score >=19.5) are associated with an increased probability
      of OE tube training success in dysphagic patients.

PMID- 29201816
TI  - Quantitative Analysis of Swallowing Function Between Dysphagia Patients and
      Healthy Subjects Using High-Resolution Manometry.
AB  - Objective: To compare swallowing function between healthy subjects and patients
      with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate
      the usefulness of HRM for detecting pharyngeal dysphagia. Methods: Seventy-five
      patients with dysphagia and 28 healthy subjects were included in this study.
      Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to
      measure pressure and timing information at the velopharynx (VP), tongue base
      (TB), and upper esophageal sphincter (UES). HRM parameters were compared between
      dysphagia and healthy groups. Optimal threshold values of significant HRM
      parameters for dysphagia were determined. Results: VP maximal pressure, TB
      maximal pressure, UES relaxation duration, and UES resting pressure were lower in
      the dysphagia group than those in healthy group. UES minimal pressure was higher
      in dysphagia group than in the healthy group. Receiver operating characteristic
      (ROC) analyses were conducted to validate optimal threshold values for
      significant HRM parameters to identify patients with pharyngeal dysphagia. With
      maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified
      with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a
      threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity
      and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure,
      dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES
      relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity,
      and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7%
      specificity for identifying dysphagia. Conclusion: We present evidence that HRM
      could be a useful evaluation tool for detecting pharyngeal dysphagia.

PMID- 29201817
TI  - Association Between Walking and Low Back Pain in the Korean Population: A Cross
      Sectional Study.
AB  - Objective: To investigate if walking is independently associated with low back
      pain (LBP) in the general population. Methods: This cross-sectional study used
      public data from the Fourth and Fifth Korean National Health and Nutrition
      Examination Survey. Subjects included 5,982 community-dwelling adults aged >=50
      years. Presence of current LBP was defined as LBP for 1 month or more in the past
      3 months. Walking was measured as total walking duration for the past week and
      subjects were divided into four quartiles. Independent effect of walking on LBP
      was determined using odds ratios (OR) adjusted for age, sex, osteoporosis,
      depression or anxiety, and radiographic lumbar spondylosis. Results: Prevalence
      of LBP was 26.4% in this population. Older people and women had higher prevalence
      of current LBP. Prevalence of obesity and osteoporosis was higher in subjects
      with current LBP and quality of life was poorer in subjects with current LBP.
      Adjusted logistic regression model revealed that older age (OR, 1.655; p=0.018),
      female sex (OR, 2.578; p<0.001), radiographic lumbar spondylosis (OR, 2.728;
      p<0.001), depression or anxiety (OR, 5.409; p<0.001), and presence of
      osteoporosis (OR, 1.467; p=0.002) were positively associated with current LBP.
      Walking decreased prevalence of current LBP proportionally (2nd quartile OR,
      0.795; 3rd quartile OR, 0.770; and 4th quartile OR, 0.686 compared with the 1st
      quartile of walking). Conclusion: Walking was negatively associated with LBP.
      Further studies are needed to reveal causal relationship of this phenomenon.

PMID- 29201818
TI  - Reliability and Validity of a New Method for Isometric Back Extensor Strength
      Evaluation Using A Hand-Held Dynamometer.
AB  - Objective: To investigate the reliability and validity of a new method for
      isometric back extensor strength measurement using a portable dynamometer.
      Methods: A chair equipped with a small portable dynamometer was designed (Power
      Track II Commander Muscle Tester). A total of 15 men (mean age, 34.8+/-7.5 years)
      and 15 women (mean age, 33.1+/-5.5 years) with no current back problems or
      previous history of back surgery were recruited. Subjects were asked to push the
      back of the chair while seated, and their isometric back extensor strength was
      measured by the portable dynamometer. Test-retest reliability was assessed with
      intraclass correlation coefficient (ICC). For the validity assessment, isometric
      back extensor strength of all subjects was measured by a widely used physical
      performance evaluation instrument, BTE PrimusRS system. The limit of agreement
      (LoA) from the Bland-Altman plot was evaluated between two methods. Results: The
      test-retest reliability was excellent (ICC=0.82; 95% confidence interval, 0.65
      0.91). The Bland-Altman plots demonstrated acceptable agreement between the two
      methods: the lower 95% LoA was -63.1 N and the upper 95% LoA was 61.1 N.
      Conclusion: This study shows that isometric back extensor strength measurement
      using a portable dynamometer has good reliability and validity.

PMID- 29201819
TI  - Asymmetric Atrophy of Paraspinal Muscles in Patients With Chronic Unilateral
      Lumbar Radiculopathy.
AB  - Objective: To assess the cross-sectional area (CSA) of the muscles for
      investigating the occurrence of asymmetry of the paraspinal (multifidus and
      erector spinae) and psoas muscles and its relation to the chronicity of
      unilateral lumbar radiculopathy using magnetic resonance imaging (MRI). Methods:
      This retrospective study was conducted between January 2012 to December 2014.
      Sixty one patients with unilateral L5 radiculopathy were enrolled: 30 patients
      had a symptom duration less than 3 months (group A) and 31 patients had a symptom
      duration of 3 months or more (group B). Axial MRI measured the CSA of the
      paraspinal and psoas muscles at the middle between the lower margin of the upper
      vertebra and upper margin of the lower vertebra, and obtained the relative CSA
      (rCSA) which is the ratio of the CSA of muscles to that of the lower margin of L4
      vertebra. Results: There were no differences in the demographics between the two
      groups. In group B, rCSA of the erector spinae at the L4-5 level, and that of
      multifidus at the L4-5 and L5-S1 levels, were significantly smaller on the
      involved side as compared with the uninvolved side. In contrast, no significant
      muscle asymmetry was observed in group A. The rCSA of the psoas was not affected
      in either group. Conclusion: The atrophy of the multifidus and erector spinae
      ipsilateral to the lumbar radiculopathy was observed only in patients suffering
      from unilateral radiculopathy for 3 months or more.

PMID- 29201820
TI  - Clinical Usefulness of X-Ray Findings for Non-specific Low Back Pain in Korean
      Farmers: FARM Study.
AB  - Objective: To elucidate the association between non-specific low back pain
      (NSLBP) and spinal X-ray findings in Korean farmers: Farmers' Cohort for
      Agricultural Work-Related Musculoskeletal disorders (FARM) study. Methods: A
      total of 835 farmers (391 males, 444 females; mean age, 56.6+/-7.4 years) without
      red-flag signs of specific LBP were recruited. Presence of LBP more than one week
      or once a month with more than moderate degree of pain severity during the last
      year was assessed with a binary questionnaire (yes or no). Spinal degenerative
      changes were classified into disc height change (DHC) of L4-5 and L5-S1 (grade 0
      5) and osteophyte formation of L5 (grade 0-5) by a radiologist based on X-ray
      findings. Additionally, spondylolisthesis, scoliosis and spondylolysis were
      assessed. Results: General prevalence of NSLBP was 40.7%, revealing a higher
      incidence of NSLBP in female and younger farmers compared to male and older
      farmers (chi2=23.3, p<0.001; chi2=4.54, p<05, respectively). Among X-ray
      findings, DHC (L5-S1) grade 4 revealed significantly higher relative risk of
      NSLBP compared to grade 0 (odds ratio, 5.00; 95% confidence interval, 2.05-12.20)
      after adjusting age and sex, while other X-ray findings were not associated with
      NSLBP. Conclusion: The NSLBP of Korean farmers was significantly related to
      lumbar disc degenerative changes, suggesting clinical usefulness of X-ray
      findings in assessing LBP in farmers.

PMID- 29201821
TI  - Effects of Early Combined Eccentric-Concentric Versus Concentric Resistance
      Training Following Total Knee Arthroplasty.
AB  - Objective: To investigate the effects of early combined eccentric-concentric (ECC
      CON) or concentric (CON) resistance training following total knee arthroplasty
      (TKA). Methods: Patients who underwent a primary TKA were randomly assigned to an
      ECC-CON group (n=16) or a CON group (n=18). All patients received early,
      progressive resistance training with five sessions per week for 2 weeks starting
      2 weeks after TKA. Isometric knee flexor and extensor strength of the surgical
      and non-surgical knees, instrumental gait analysis for spatiotemporal parameters,
      6-Minute Walk Test (6MWT), Timed Up and Go Test (TUG), Timed Stair Climbing Test
      (SCT) were used to evaluate performance-based physical function. The Western
      Ontario McMaster Universities Osteoarthritis Index (WOMAC) and EuroQOL five
      dimensions (EQ-5D) questionnaire were used to evaluate self-reported physical
      function and self-reported quality of life. All patients underwent these
      evaluations before and 1 month after TKA. Results: The ECC-CON group showed
      clinically meaningful improvements in extensor peak torque (PT) of the non
      surgical knee, gait speed, and 6MWT from preoperative values. The CON group had
      an increase in H/Q ratio of the surgical knee and improvement in SCT-ascent
      postoperatively. Both groups showed significant improvements in WOMAC-Pain,
      function, and EQ-5D scores. Although extensor PT of the surgical knee did not
      reach the preoperative level in either group, the postoperative change was
      significantly less in the ECC-CON group than the CON group. Conclusion: Early
      combined ECC-CON resistance training minimizes the loss in quadriceps strength of
      the surgical knee and improves endurance and gait speed after TKA.

PMID- 29201822
TI  - Effect of Extracorporeal Shockwave Therapy Versus Intra-articular Injections of
      Hyaluronic Acid for the Treatment of Knee Osteoarthritis.
AB  - Objective: To evaluate and compare the effects and outcomes of extracorporeal
      shock wave therapy (ESWT) and intra-articular injections of hyaluronic acid (HA)
      in patients with knee osteoarthritis (OA). Methods: Of the 78 patients recruited
      for the study, 61 patients met the inclusion criteria. The enrolled patients were
      randomly divided into two groups: the ESWT group and the HA group. The ESWT group
      underwent 3 sessions of 1,000 shockwave pulses performed on the affected knee
      with the dosage adjusted to 0.05 mJ/mm2 energy. The HA group was administered
      intra-articular HA once a week for 3 weeks with a 1-week interval between each
      treatment. The results were measured with the visual analogue scale (VAS),
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne
      index, 40-m fast-paced walk test, and stair-climb test (SCT). A baseline for each
      test was measured before treatment and then the effects of the treatments were
      measured by each test at 1 and 3 months after treatment. Results: In both groups,
      the scores of the VAS, WOMAC, Lequesne index, 40-m fast-paced walk test, and SCT
      were significantly improved in a time-dependent manner (p<0.01). There were no
      statistically significant differences measured at 1 and 3 months after treatment
      between the two groups (p>0.05). Conclusion: The ESWT can be an alternative
      treatment to reduce pain and improve physical functions in patients with knee OA.

PMID- 29201823
TI  - Speech and Linguistic Features of Children With Articulation Disorder.
AB  - Objective: To analyze speech and linguistic features in children with
      articulation disorder characterized by consonant and vowel phonological errors.
      Methods: Between February 2007 and June 2015, 117 children who showed
      articulation disorder were selected for the study. Based on comprehensive speech
      and language assessments, the subjects were classified into articulation
      dysfunction (AD), or AD overlapping with language delay. Detailed information of
      articulation, including percentage of consonants correct (PCC) and normal
      percentage of variable consonants derived from the Assessment of Phonology and
      Articulation for Children test, were compared between the two groups. Results:
      Totally, 55 children were diagnosed as AD and 62 as AD with language delay. Mean
      PCC was not significantly different between the two groups. In both groups, the
      acquisition order of consonants followed the universal developmental sequence.
      However, differences were observed in the nasal & plosive consonants abnormality
      between the two groups. When adjusted to their delayed language level in AD with
      language delay group, 53% of children had appropriate articulation function for
      their expressive language level. Conclusion: Speech and linguistic
      characteristics in children with articulation disorder were variable. Therefore,
      comprehensive assessment is required in children with inaccurate pronunciation,
      and a proper treatment plan based on the results of assessment should be
      followed.

PMID- 29201824
TI  - Assessment of Preterm Infants Using the Bayley-III Scales in Korea.
AB  - Objective: To assess the well-being of preterm newborns using the Bayley-III
      scales in a Korean-based population, and to evaluate the perinatal risk factors
      influencing developmental outcome. Methods: Using the Bayley-III scales, we
      assessed 120 preterm infants who were referred for evaluation of
      neurodevelopmental performance. We subdivided them into an extremely preterm
      group (n=18) and a very/moderate to late preterm group (n=102). Bayley-III mean
      scores and the rate of infants showing a delay were compared for both groups. The
      relationship between perinatal risk factors and Bayley-III scores was analyzed.
      The risk factors were considered as very low birth weight, history of neonatal
      medical problems, and abnormal radiologic findings in brain magnetic resonance
      images (MRIs). Results: Although no significant differences in mean scores were
      observed between the extremely preterm group and the very/moderate to late
      preterm group, the rate of babies showing developmental delay in motor composite
      scores was significantly higher in the extremely preterm group. The proportions
      of preterm infants with cognitive, language, and motor delays were 38.3%, 26.7%,
      and 35.0%, respectively. Very low birth weight was a significant risk factor for
      low cognitive, language, and motor composite scores. Also, abnormal radiologic
      findings on brain MRI were significant indicators of lower motor composite
      scores. Conclusion: Cognitive development was the most frequently delayed domain
      in preterm infants and motor development was more frequently delayed in the
      extremely preterm group. The very low birth weight and abnormal radiologic
      findings in brain MRI were predictive factors for neurodevelopmental outcome.

PMID- 29201826
TI  - Translation, Cross-cultural Adaptation and Psychometric Validation of the Korean
      Language Cardiac Rehabilitation Barriers Scale (CRBS-K).
AB  - Objective: To perform a translation and cross-cultural adaptation of the Cardiac
      Rehabilitation Barriers Scale (CRBS) for use in Korea, followed by psychometric
      validation. The CRBS was developed to assess patients' perception of the degree
      to which patient, provider and health system-level barriers affect their cardiac
      rehabilitation (CR) participation. Methods: The CRBS consists of 21 items
      (barriers to adherence) rated on a 5-point Likert scale. The first phase was to
      translate and cross-culturally adapt the CRBS to the Korean language. After back
      translation, both versions were reviewed by a committee. The face validity was
      assessed in a sample of Korean patients (n=53) with history of acute myocardial
      infarction that did not participate in CR through semi-structured interviews. The
      second phase was to assess the construct and criterion validity of the Korean
      translation as well as internal reliability, through administration of the
      translated version in 104 patients, principle component analysis with varimax
      rotation and cross-referencing against CR use, respectively. Results: The length,
      readability, and clarity of the questionnaire were rated well, demonstrating face
      validity. Analysis revealed a six-factor solution, demonstrating construct
      validity. Cronbach's alpha was greater than 0.65. Barriers rated highest included
      not knowing about CR and not being contacted by a program. The mean CRBS score
      was significantly higher among non-attendees (2.71+/-0.26) than CR attendees
      (2.51+/-0.18) (p<0.01). Conclusion: The Korean version of CRBS has demonstrated
      face, content and criterion validity, suggesting it may be useful for assessing
      barriers to CR utilization in Korea.

PMID- 29201825
TI  - The Validity of the Bayley-III and DDST-II in Preterm Infants With
      Neurodevelopmental Impairment: A Pilot Study.
AB  - Objective: To identify the usefulness of both the Bayley Scales of Infant and
      Toddler Development, 3rd edition (Bayley-III) and Denver Developmental Screening
      Test II (DDST-II) in preterm babies with neurodevelopmental impairment,
      considering the detection rate as regulation of criteria. Methods: Retrospective
      medical chart reviews which included the Bayley-III and DDST-II, were conducted
      for 69 preterm babies. Detection rate of neurodevelopmental impairment in preterm
      babies were investigated by modulating scaled score of the Bayley-III. The
      detection rate of DDST-II was identified by regarding more than 1 caution as an
      abnormality. Then detection rates of each corrected age group were verified using
      conventional criteria. Results: When applying conventional criteria, 22 infants
      and 35 infants were detected as preterm babies with neurodevelopmental
      impairment, as per the Bayley-III and DDST-II evaluation, respectively. Detection
      rates increased by applying abnormal criteria that specified as less than 11
      points in the Bayley-III scaled score. In DDST-II, detection rates rose from 50%
      to 68.6% using modified criteria. The detection rates were highest when performed
      after 12 months corrected age, being 100% in DDST II. The detection rate also
      increased when applying the modified criteria in both the Bayley-III and DDST-II.
      Conclusion: Accurate neurologic examination is more important for detection of
      preterm babies with neurodevelopmental impairment. We suggest further studies for
      the accurate modification of the detection criteria in DDST-II and the Bayley-III
      for preterm babies.

PMID- 29201827
TI  - Lumbar Scoliosis in Patients With Breast Cancer: Prevalence and Relationship With
      Breast Cancer Treatment, Age, Bone Mineral Density, and Body Mass Index.
AB  - Objective: To identify the prevalence of lumbar scoliosis in breast cancer
      patients and to investigate the potential risk factors of lumbar scoliosis.
      Methods: A retrospective chart review was performed in breast cancer patients
      aged more than 40 years who underwent dual energy X-ray absorptiometry (DEXA)
      scanning between January 2014 and December 2014. We divided the patients into
      control and experimental groups in order to investigate the influence of breast
      cancer treatment. The curvature of the lumbar spine was measured by using the
      Cobb method on a DEXA scan. Scoliosis was defined by the presence of a curvature
      10 degrees  or larger. The variables, including age, bone mineral density (BMD),
      body mass index (BMI), and breast cancer treatments, were also obtained from the
      medical chart. Prevalence of lumbar scoliosis was evaluated, and it was compared
      between the two groups. The relationships between lumbar scoliosis and these
      variables were also investigated. Results: Lumbar scoliosis was present in 16 out
      of our 652 breast cancer patients. There was no difference in the prevalence of
      lumbar scoliosis between the control group (7/316) and the experimental group
      (9/336) (p=0.70). According to the logistic regression analysis, lumbar scoliosis
      had no significant association with operation, chemotherapy, hormone therapy,
      BMI, and BMD (p>0.05). However, age showed a significant relationship with
      prevalence of lumbar scoliosis (p<0.001; odds ratio, 1.11; 95% confidence
      interval, 1.054-1.170). Conclusion: Prevalence of lumbar scoliosis in patients
      with breast cancer was 2.45%. Lumbar scoliosis had no association with breast
      cancer treatments, BMD, and BMI. Age was the only factor related to the
      prevalence of lumbar scoliosis.

PMID- 29201828
TI  - Hand Functions of Myoelectric and 3D-Printed Pressure-Sensored Prosthetics: A
      Comparative Study.
AB  - The loss of an upper limb significantly limits the functional activities of daily
      living. A huge emphasis is placed on the manipulation, shape, weight, and comfort
      of a prosthesis, to enable its use as an inherent body part. Even with
      technological advances, customized upper-extremity myoelectric prosthesis remain
      heavy and expensive. The high cost of upper-extremity prosthesis is an especially
      steep economic barrier for patients. Three-dimensional (3D) printing is a
      promising avenue for reducing the cost of prosthesis. We applied 3D-printed
      pressure-sensored prosthetics to a traumatic transradial amputee, and compared
      the hand functions with a customized myoelectric prosthesis. The 3D-printed
      pressure-sensored prosthetics showed low grip strength and decreased dexterity
      compared to the conventional myoelectric prosthesis. Although there were a few
      limitations, the fabrication of prosthesis with 3D printing technology can
      overcome previous problems such as high production cost, long fabrication period
      and heavy weight.

PMID- 29201830
TI  - Lymphedema Associated With Primary Amyloidosis: A Case Study.
AB  - We reported on a 60-year-old man presenting lymphedema of both lower extremities
      and scrotum for 3 years with unknown cause. We took a computed tomography scan of
      the lower extremities as a follow-up. There were diffuse subcutaneous edema in
      both lower extremities and multiple enlarged lymph nodes along the para-aortic
      and bilateral inguinal areas. For further evaluation, biopsy of an enlarged
      inguinal lymph node was taken, yielding a diagnosis of primary amyloidosis. A
      treatment of chemotherapy for amyloidosis was recommended for him. To our
      knowledge, this is the first report of lymphedema presenting with primary
      amyloidosis in Asia. This case suggests that primary amyloidosis could be one of
      the differential diagnoses in patients with lymphedema in the lower extremities.

PMID- 29201829
TI  - Patient With Delayed Development Resulting From De Novo Duplication of 7q36.1
      q36.3 and Deletion of 9p24.3.
AB  - Patients with a duplication from 7q36 to the terminus or a deletion of 9p24 have
      been reported, whereas those harboring both mutations have not. Here, we report a
      patient with simultaneous de novo 7q36.1-q36.3 duplication and 9p24.3 deletion. A
      6-year-old boy presented with speech developmental delay, microcephaly, and
      dysmorphic features, including a long face and small nose. Chromosome and array
      comparative genomic hybridization analyses revealed 46,XY,dup(7)(q36.1-q36.3) and
      del(9)(p24.3). The sizes of the duplication and deletion were 9.9 Mb and 1.9 Mb,
      respectively. The duplication of chromosome 7 contained 68 known genes, of which
      3 are related with entries in the Developmental Disorders Genotype-to-Phenotype
      (DDG2P) database. The deletion of chromosome 9 contained 6 known genes, of which
      2 are in the DDG2P database. We investigated the genotype and phenotype in this
      patient, and reviewed the relevant literatures for possible clinical presentation
      in these variations.

PMID- 29201831
TI  - An Infantile Case of Sandhoff Disease Presenting With Swallowing Difficulty.
AB  - Infants with Sandhoff disease typically appear normal until 3-6 months of age. As
      the disease progresses, they present with symptoms such as loss of motor skills,
      exaggerated startle response to loud noise, seizures, visual loss, and paralysis.
      We encountered a rare case of a 22-month-old girl with Sandhoff disease
      characterized by progressive motor weakness and dysphagia, who initially showed
      signs of aspiration at 20 months of age. The major problems related to dysphagia
      were oromotor dysfunction and abnormal feeding posture. Within 3 months of
      identification of difficulty in swallowing, the patient showed a significant
      decrease in food intake, with rapid deterioration of nutritional status. We
      report our case with a review of the literature.

PMID- 29201832
TI  - Letter to the Editor: Successful Extubation After Weaning Failure by Noninvasive
      Ventilation in Patients With Neuromuscular Disease - Do We Appreciate the Bigger
      Picture?

PMID- 29201834
TI  - Correction: Nerve Conduction Study of the Distal Branches of the Superficial
      Radial Nerve.
AB  - [This corrects the article on p. 557 in vol. 31.].

PMID- 29201833
TI  - In Reply: Successful Extubation After Weaning Failure by Non-invasive Ventilation
      in Patients With Neurmuscular Disease - Do We Appreciate the Bigger Picture?

PMID- 29201835
TI  - Correction: Idiopathic Retroperitoneal Fibrosis With Myofascial Pain Syndrome: A
      Case Report.
AB  - [This corrects the article on p. 123 in vol. 33.].

PMID- 29201836
TI  - Traumatic Cerebrospinal Fluid Leak: Diagnosis and Management.
AB  - Cerebrospinal fluid (CSF) leaks are one of the common complications after
      traumatic brain injuries (TBI). The risks of CSF leaks can be detrimental to the
      outcomes of the patients. Early diagnosis and proper management is imperative for
      it is strongly associated with a better long-term prognosis of the patients.
      Diagnostic tools for CSF leaks are still under debate. Nevertheless, many reports
      of successful treatments for CSF leaks have been published with introduction of
      various repair techniques for leakage sites even though it is surgically
      challenging. Hereby, we review about the pathophysiology, manifestations as well
      as the update of the clinical diagnosis and current management of CSF leaks.

PMID- 29201837
TI  - Expression of Aquaporin 1 and 4 in the Choroid Plexus and Brain Parenchyma of
      Kaolin-Induced Hydrocephalic Rats.
AB  - Objective: Aquaporin (AQP) is a recently discovered protein that regulates water
      homeostasis. The present study examines changes in AQP 1 and 4 in kaolin induced
      experimental hydrocephalic rats to elucidate the pathophysiology of water
      homeostasis in the disease. Methods: Hydrocephalus was induced by percutaneous
      intracisternal injection of kaolin. The brain parenchyma and choroid plexus were
      obtained at 3, 7, 14 and 30 days after injection. Protein expressions of AQP 1
      and 4 were measured by western blot, immunohistochemistry (IHC) and
      immunofluorescence (IF) stains. Results: In the choroid plexus of the kaolin
      induced hydrocephalus group, AQP 1 expression identified by western blot
      exhibited sharp decrease in the early stage (55% by the 3rd day and 22% by the
      7th day), but indicated a 2.2-fold increase in the later stage (30th day) in
      comparison with control groups. In the parenchyma, a quantitative measurement of
      AQP 4 expression revealed variable results on the 3rd and 7th days, but indicated
      expression 2.1 times higher than the control in the later stage (30th day). In
      addition, the IHC and IF findings supported the patterns of expression of AQP 1
      in the choroid plexus and AQP 4 in the parenchyma. Conclusion: Expression of AQP
      1 decreased sharply in the choroid plexus of acute hydrocephalus rats and
      increased at later stages. Expression of AQP 4 in the brain parenchyma was
      variable in the early stage in the hydrocephalus group, but was higher than in
      the control in the later stage. These findings suggest a compensating role of
      AQPs in water physiology in hydrocephalus.

PMID- 29201838
TI  - Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative
      Stress.
AB  - Objective: Traumatic brain injury causes tissue damage, breakdown of cerebral
      blood flow and metabolic regulation. This study aims to investigate the
      protective influence of antioxidant Ganoderma lucidum (G. lucidum)
      polysaccharides (GLPs) on brain injury in brain-traumatized rats. Methods:
      Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g
      weight from 1 m height. Groups were categorized as control, G. lucidum, trauma,
      trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were
      dissected from anesthetized rats 7 days after injury. For biochemical analysis,
      malondialdehyde, glutathione and myeloperoxidase values were measured. Results:
      In histopathological examination, neuronal damage in brain cortex and changes in
      blood brain barrier were observed. In the analysis of immunohistochemical and
      western blot, p38 mitogen-activated protein kinase, vascular endothelial growth
      factor and cluster of differentiation 68 expression levels were shown. These
      analyzes demonstrated the beneficial effects of GLPs on brain injury. Conclusion:
      We propose that GLPs treatment after brain injury could be an alternative
      treatment to decraseing inflammation and edema, preventing neuronal and glial
      cells degeneration if given in appropriate dosage and in particular time
      intervals.

PMID- 29201839
TI  - Trauma Patterns of Drowning after Falling from Bridges over Han River.
AB  - Objective: Recently, the number of patients who fell or jumped from bridges over
      Han River has rapidly increased. However, the injury patterns and outcomes of
      these patients have been poorly characterized. The aim of this study was to
      determine the injury characteristics of these patients. Methods: We reviewed the
      medical records of all patients who were transferred to the Emergency Room due to
      jumping or falling from bridges over Han River between 2011 and 2015. Results: A
      total of 203 patients were included. Among them, 14 (6.9%) patients were dead on
      arrival, 51 (25.1%) patients were expired in the hospital, and 138 (70%) patients
      were discharged alive, including a patient who had severe neurologic sequelae
      after resuscitation. Skeletal and internal organ injuries were identified based
      on radiologic images. The most injured organ was thorax (58.1%), followed by
      spine (23.1%), abdomen (11.1%), extremity (7.7%), and cranium (5.2%). Chest
      tubing for pneumothorax or hemothorax was performed in four (2.9%) patients.
      Surgical intervention was needed for four patients (2.9%). Conclusion: Trauma
      patterns were concentrating on the thorax and spine regions. Therefore, complete
      radiographic evaluation should be performed for these patients.

PMID- 29201840
TI  - Epidemiology and Risk Factors for Bicycle-Related Severe Head Injury: A Single
      Center Experience.
AB  - Objective: Head injury is the main cause of death and severe disability in
      bicycle-related injuries. The purpose of this study was to compare the
      demographic characteristics and injury mechanisms of bicycle-related head
      injuries according to the severity and outcome and determine the main risk
      factors and common types of accompanying injuries. Methods: A total of 205
      patients who were admitted to the neurosurgery department of our hospital for
      bicycle-related head injuries between 2007 and 2016 were analyzed. We categorized
      the patients into two groups according to severity and outcome of head injury,
      and then identified the differences in age, sex, and cause of injury between the
      two groups. Results: Collisions with a motor vehicle increased the risk of severe
      head injury (p=0.011), resulted in poor outcomes (Glasgow Outcome Scale [GOS]
      <=3; p=0.022), and caused more accompanying chest/abdominal (p<0.001) and
      pelvic/lower extremity injuries (p=0.001) than other mechanisms. Older age and
      high grade of head injury severity resulted in poor outcomes (p=0.028 and
      p<0.001, respectively), and caused more accompanying chest/abdominal injuries
      (p<0.032 and p<0.001, respectively) compared with younger age and low grade of
      head injury severity. Conclusion: In bicycle-related head injuries, collision
      with motor vehicle is one of the most important risk factor for high grade of
      head injury severity and outcome. In addition, bicycle-related head injuries are
      often accompanied by injuries of other parts of the body.

PMID- 29201841
TI  - The Combined Use of Cardiac Output and Intracranial Pressure Monitoring to
      Maintain Optimal Cerebral Perfusion Pressure and Minimize Complications for
      Severe Traumatic Brain Injury.
AB  - Objective: To show the effect of dual monitoring including cardiac output (CO)
      and intracranial pressure (ICP) monitoring for severe traumatic brain injury
      (TBI) patiens. We hypothesized that meticulous treatment using dual monitoring is
      effective to sustain maintain minimal intensive care unit (ICU) complications and
      maintain optimal ICP and cerebral perfusion pressure (CPP) for severe TBI
      patiens. Methods: We included severe TBI, below Glasgow Coma Scale (GCS) 8 and
      head abbreviation injury scale (AIS) >4 and performed decompressive craniectomy
      at trauma ICU of our hospital. We collected the demographic data, head AIS,
      injury severity score (ISS), initial GCS, ICU stay, sedation duration, fluid
      therapy related complications, Glasgow Outcome Scale (GOS) at 3 months and
      variable parameters of ICP and CO monitor. Results: Thirty patients with severe
      TBI were initially selected. Thirteen patients were excluded because 10 patients
      had fixed pupillary reflexes and 3 patients had uncontrolled ICP due to severe
      brain edema. Overall 17 patients had head AIS 5 except 2 patients and 10 patients
      (58.8%) had multiple traumas as mean ISS 29.1. Overall complication rate of the
      patients was 64.7%. Among the parameters of CO monitoring, high stroke volume
      variation is associated with fluid therapy related complications (p=0.043) and
      low cardiac contractibility is associated with these complications (p=0.009)
      statistically. Conclusion: Combined use of CO and ICP monitors in severe TBI
      patients who could be necessary to decompressive craniectomy and postoperative
      sedation is good alternative methods to maintain an adequate ICP and CPP and
      reduce fluid therapy related complications during postoperative ICU care.

PMID- 29201842
TI  - Clinical Features of Interhemispheric Subdural Hematomas.
AB  - Objective: Interhemispheric subdural hematoma (IHSDH) is uncommon, because of
      their unusual location. However, it is a distinct lesion with its unique
      characteristics. We investigated clinical features and outcomes of consecutive 42
      patients with IHSDH, retrospectively. Methods: From 2006 to 2015, we treated 105
      patients with IHSDH. All patients were diagnosed by computed tomography (CT) or
      magnetic resonance imaging. We selected 42 patients with thick (3 mm or more)
      IHSDH. We retrospectively reviewed the clinical and radiological findings,
      management and outcomes. Results: The male to female ratio was 2:1. Two thirds of
      the patients were over 60 years old. Slip or fall was the most common cause of
      trauma. The level of consciousness on admission was Glasgow Coma Scale (GCS) 13
      to 15 in 25 patients. The most common symptom was headache. All IHSDH was
      hyperdense in CT at the time of diagnosis. IHSDH frequently accompanied convexity
      subdural hematoma. The outcome was favorable in 27 patients, however, six
      patients were expired. Twenty-two patients were managed conservatively. Surgery
      was performed in ten patients to remove the concurrent lesion. The outcome was
      poor in spontaneous one, patients with low GCS, and patients with conservative
      treatment. Conclusion: IHSDH is rare especially the isolated one. The outcome was
      dependent to the severity of injury. Surgery may be helpful to remove the
      concurrent mass lesion, however, conservative treatment is generally preferred.

PMID- 29201843
TI  - Clinical Features and Outcomes of Bilateral Decompression Surgery for Immediate
      Contralateral Hematoma after Craniectomy Following Acute Subdural Hematoma.
AB  - Objective: Immediate contralateral epidural hematoma (EDH) and traumatic
      intracerebral hematoma (T-ICH) after craniectomy for traumatic subdural hematoma
      (SDH) are rare but devastating post-operative complications. Their clinical
      features and outcomes are not well studied. In this report, we present the
      clinical features and outcomes of immediate contralateral acute hematoma cases
      requiring a second operation. Methods: This study includes 10 cases of immediate
      contralateral EDH and T-ICH following bilateral craniectomy for the evacuation of
      traumatic SDH and contralateral hematoma between 2004 and 2015. Their medical
      records and radiographic findings were reviewed and analyzed retrospectively.
      Results: Ten of the 528 patients (1.89%) who underwent craniectomy for the
      evacuation of traumatic SDH developed post-operative EDH (n=5), T-ICH (n=5). The
      trauma was caused by a fall in 5 patients and by a traffic accident in 5
      patients. The patients who suffered trauma due to pedestrian accidents died.
      Seven patients had a low admission Glasgow Coma Scale (GCS; GCS<=8) score in the
      preoperative state (average admission GCS, 7.7; average discharge GCS, 3.4; and
      average discharge Glasgow Outcome Scale, 2.0). Severe intra-operative brain
      swelling was noted in all patients, while skull fracture was observed in 8.
      Multiple associated injuries and medication for heart disease were characteristic
      of patients who died. Conclusion: The prognosis of delayed contralateral hematoma
      was very poor. Multiple associated injuries, past medical history and traffic
      accidents, especially pedestrians were seemed to be associated with higher
      mortality rates. Finally, contralateral skull fractures can indicate high risk of
      delayed contralateral acute intracranial hematoma.

PMID- 29201844
TI  - Factors Affecting Optimal Time of Cranioplasty: Brain Sunken Ratio.
AB  - Objective: After a rigorous management of increased intracranial pressure by
      decompressive craniectomy (DC), cranioplasty (CP) is usually carried out for
      functional and cosmetic purposes. However, the optimal timing of CP remains
      controversial. Our study aims to analyze the relationship between the optimal
      timing of CP and the post-operative complications. Methods: From January 2013 to
      December 2015, ninety patients who underwent CP in a single institution were
      analyzed. We set the independent variables as follows: 1) patient
      characteristics; 2) the time interval between the DC and CP; 3) operation time;
      4) anesthesia time; and 5) pre-operative computed tomography (CT) findings such
      as a degree of sunken brain by ratio of A (the median length from scalp to
      midline) to B (the length from midline to inner table of skull at this level).
      The dependent variables of this study are the event of post-operative
      complications. Results: The overall complication rate was 33.3%. There was no
      statistical significance in the time interval between the DC and CP in the groups
      with and without complications of CP (p=0.632). However, there was a significant
      statistical difference in the degree of sunken brain by ratio (A/B) between the
      two groups (p<0.001). Conclusion: From this study, we conclude that it is better
      to determine the optimal timing of CP by the pre-operative CT finding than by the
      time interval between the DC and CP. Hereby, we suggest a potentially useful
      determinant of optimal timing of CP.

PMID- 29201845
TI  - Kummell's Disease Treated with Percutaneous Vertebroplasty: Minimum 1 Year Follow
      Up.
AB  - Objective: To evaluate the radiographic and clinical outcomes of percutaneous
      vertebroplasty (PVP) in patients with Kummell's disease. Methods: A retrospective
      review was conducted for 19 vertebrae in 18 patients, between January 2012 and
      June 2016. A visual analogue scale (VAS) score was used to determine each
      patient's subjective level of pain (0=no pain to 10=severe pain) preoperative,
      immediately postoperative and at the last follow-up (at least 12 months after
      PVP).Radiographic parameters such as regional and global kyphotic angle, lumbar
      lordosis (LL), thoracolumbar junction (TLJ) angle, vertebral height, cement
      leakage, refracture, and adjacent level fracture were evaluated by the clinician
      preoperative, immediate postoperative and at the last follow-up. Results: The
      mean VAS score significantly decreased after PVP and the decrease was maintained
      through to the final follow-up (p<0.05). However, the regional and global
      kyphotic angle, LL, and TLJ angle were not improved. Cement leakage was observed
      in 5 cases (26.3%): however, there were no cases of cement leakage into the
      spinal canal. No neurological deterioration was observed, even among patients
      with cement leakage. Adjacent level fractures were detected in 3 cases (15.8%).
      Conclusion: PVP can be considered as an effective treatment option for pain
      relief and maintenance of sagittal balance in patients with Kummell's disease.

PMID- 29201846
TI  - Comparison of Surgical Results between Soft Ruptured Disc and Foraminal Stenosis
      Patients in Posterior Cervical Laminoforaminotomy.
AB  - Objective: Posterior cervical laminoforaminotomy is used to relieve cervical
      nerve root compression caused by a laterally herniated soft cervical disc or
      spondylotic spur and its several advantages and disadvantages compared with
      anterior cervical discectomy were reported. We compared surgical results between
      soft ruptured disc and foraminal stenosis in posterior cervical
      laminoforaminotomy. Methods: We performed a retrospective review of 47 patients
      performed single level posterior cervical laminoforaminotomy for cervical
      radiculopathy between 2004 and 2012. We divided these patients into two groups,
      Group A: 27 patients for ruptured disc and Group B: 20 patients for foraminal
      stenosis and analyzed the demographic factors, amount of medial facetectomy,
      postoperative instability with neck pain and clinical outcomes. Results:
      According to the modified Odom's criteria, laminoforaminotomy for the ruptured
      disc showed 92.6% excellent results and 7.4% good results. For the foraminal
      stenosis, it was 55.0% excellent and 25.0% good results, which was statistically
      significant. However when both groups were included, overall success rate showed
      91.5%. The extent of medial facetectomy for ruptured disc (31.2%) was smaller
      than for stenosis (48.8%) and it was statistically significant. Thirteen patients
      complained of postoperative neck pain for 2 months. There was no instability on
      dynamic X-ray until the last follow up period and we had two cases complications
      (4.3%). Conclusion: Although the extent of facetectomy for ruptured disc was
      smaller than it for stenosis, posterior laminoforaminotomy for the ruptured disc
      showed the better outcomes than foraminal stenosis.

PMID- 29201847
TI  - The Efficacy of Fentanyl Transdermal Patch as the First-Line Medicine for the
      Conservative Treatment of Osteoporotic Compression Fracture.
AB  - Objective: There are no strong guidelines on how long or how we should undertake
      conservative treatment during the acute period of an osteoporotic vertebral
      compression fracture (VCF). Methods: We treated 202 patients with conservative
      treatment on VCF from March 2012 to August 2015. On inclusion criteria, 75
      patients (22 males and 53 females) were included in the final analysis. After
      admission, a transdermal fentanyl patch with low dose (12.5 ug) application was
      attempted in all patients. In an unresponsive patient, the fentanyl patch was
      increased by 25 ug. After identifying the tolerable toilet ambulation of the
      patient without any assistance, hospital discharge was recommended. We classified
      two patient groups into one favorable group and one unfavorable group and
      compared several clinical and radiological factors. Results: Among 75 patients,
      the clinical outcome of 57 patients (76%) was favorable, but that of 18 patients
      (24%) was unfavorable. In clinical outcomes, the numeric rating scale at 6 and 12
      months and Odom's criteria at 12 months was significantly different between the
      favorable and the unfavorable groups. The dose of the patches used showed
      statistically significant differences between the two groups (p=0.001).
      Conclusion: The only statistically significant affecting factor for an
      unfavorable outcome was the use of a higher dose fentanyl patch. Our data
      inferred that the unresponsiveness to a low-dose fentanyl patch could be helpful
      to select patients necessary for percutaneous vertebroplasty or kyphoplasty.

PMID- 29201848
TI  - Intraoperative Transcranial Sonography for Detection of Contralateral Hematoma
      Volume Change in Patients with Traumatic Brain Injury.
AB  - The authors present two clinical cases, in which intraoperative transcranial
      sonography (TCS) was used to detect a change in contralateral hematoma volume. A
      51-year-old female and a 5-year-old male underwent osteoplastic craniotomy for
      epidural hematoma removal. Scant contralateral hematoma was evident by
      preoperative computed tomography in both patients. Intraoperative TCS was used to
      detect changes in contralateral hematomas. After observing a volume change in one
      case, a second operation was performed immediately. Based in this experience, the
      authors recommend intraoperative TCS for the detection of contralateral hematoma
      volume changes.

PMID- 29201849
TI  - Concurrent Surgery of Craniectomy and Splenectomy as Initial Treatment in Severe
      Traumatic Head Injury: A Case Report.
AB  - It is not a common case for neurosurgery department and the other departments to
      perform joint operation at the same time. Patients with severe head injury are a
      condition in which vital signs are unstable due to severe brain swelling and
      increased intracranial pressure, and emergency surgery is required. A 44-year-old
      man visited the trauma center with a motorcycle accident. The Glasgow Coma Scale
      score at the time of emergency department was 3 points, and the pupil was fixed
      at 6 mm on both sides. His medical history was unknown. His vital signs including
      blood pressure (BP), heart rate, respiratory rate and oxygen saturation were
      stable. Associated injuries included multiple fractures of whole body. Brain
      computed tomography revealed subarachnoid hemorrhage, intraventricular hemorrhage
      and severe cerebral edema. During the preparation of the craniectomy, abdominal
      ultrasonography performed because of decreased BP resulted in a large amount of
      hemoperitoneum. The bi-coronal craniectomy and splenectomy were performed
      simultaneously for about 4 hours. After fifty days of treatment, he was
      discharged with Glasgow Outcome Scale-extended 4 points and is undergoing
      rehabilitation. In severe polytrauma patients, active concurrent surgery is a
      good method to save their lives.

PMID- 29201850
TI  - Remote Hemorrhage after Burr Hole Drainage of Chronic Subdural Hematoma.
AB  - Chronic subdural hematoma (CSDH) and symptomatic subdural hygroma are common
      diseases that require neurosurgical management. Burr hole trephination is the
      most popular surgical treatment for CSDH and subdural hygroma because of a low
      recurrence rate and low morbidity compared with craniotomy with membranectomy,
      and twist-drill craniotomy. Many reports suggest that placing a catheter in the
      subdural space for drainage can further reduce the rate of recurrence; however,
      complications associated with this type of drainage include acute subdural
      hematoma, cortical injury, and infection. Remote hemorrhage due to overdrainage
      of cerebrospinal fluid (CSF) is another possible complication of burr hole
      trephination with catheter drainage that has rarely been reported. Here, we
      present 2 cases of remote hemorrhages following burr hole trephination with
      catheter drainage for the treatment of CSDH and symptomatic subdural hygroma. One
      patient developed intracerebral hemorrhage and subarachnoid hemorrhage in the
      contralateral hemisphere, while another patient developed remote hemorrhage 3
      days after the procedure due to the sudden drainage of a large amount of subdural
      fluid over a 24-hour period. These findings suggest that catheter drainage should
      be carefully monitored to avoid overdrainage of CSF after burr hole trephination.

PMID- 29201851
TI  - Postoperative Subarachnoid Hemorrhage and Multipunctate Intracerebral Hemorrhages
      Following Evacuation of Bilateral Chronic Subdural Hematomas.
AB  - Chronic subdural hematoma (CSDH) can be easily treated by burr hole surgery.
      However, several complications including intracerebral hemorrhage (ICH),
      subarachnoid hemorrhage (SAH), and acute subdural hematoma are rare after
      evacuation of a CSDH. A 77-year-old man was admitted with right hemiparesis and
      dysarthria. A brain computed tomography (CT) scan revealed a bilateral CSDH with
      midline shifting toward the right side. The patient got the burr hole
      trephination with the catheters insertion in the both sides of parietal area
      under the local anesthesia. After burr hole surgery immediately, he developed
      left side weakness and decreased level of consciousness. Repeat CT scans detected
      a diffuse SAH and multiple small ICHs. He was treated conservatively and fully
      recovered at discharge after 1 month. To avoid these complications, slow and
      gradual drainage of the CSDH is needed. The authors report a rare case of SAH and
      multipunctate ICHs in both cerebral hemispheres after evacuation of a bilateral
      CSDH.

PMID- 29201852
TI  - Chronic Brain-Dead Patients Who Exhibit Lazarus Sign.
AB  - Lazarus sign, a complex reflex movement of the upper limbs after brain death, is
      a rare occurrence. We report two patients who showed a Lazarus sign following a
      diagnosis of brain death. It has been accepted that cardiac arrest usually occurs
      within 1 week after brain death; however, the two patients described herein
      survived for over 100 days after brain death was diagnosed. This report is
      intended to examine the relationship between the Lazarus sign and long-term
      survival after brain death, as well as to share our rare experience.

PMID- 29201853
TI  - Proper Management of Posttraumatic Tension Pneumocephalus.
AB  - Pneumocephalus is commonly seen after craniofacial injury. The pathogenesis of
      pneumocephalus has been debated as to whether it was caused by ball valve effect
      or combined episodic increased pressure within the nasopharynx on coughing.
      Discontinuous exchange of air and cerebrospinal fluid due to "inverted bottle"
      effect is assumed to be the cause of it. Delayed tension pneumocephalus is not
      common, but it requires an active management in order to prevent serious
      complication. We represent a clinical case of a 57-year-old male patient who fell
      down from 3 m height, complicated by tension pneumocephalus on 5 months after
      trauma. We recommend a surgical intervention, but the patient did not want that
      so we observe the patient. The patient was underwent seizure and meningitis after
      7 months after trauma, he came on emergency room on stupor mentality. Tension
      pneumocephalus may result in a neurologic disturbance due to continued air
      entrainment and it significantly the likelihood of intracranial infection caused
      by continued open channel. Tension pneumocephalus threat a life, so need a
      neurosurgical emergency surgical intervention.

PMID- 29201854
TI  - Traumatic Intracerebral and Subarachnoid Hemorrhage Due to a Ruptured
      Pseudoaneurysm of Middle Meningeal Artery Accompanied by a Medial Sphenoid Wing
      Dural Arteriovenous Fistula.
AB  - Traumatic pseudoaneurysms of middle meningeal artery (MMA) and medial sphenoid
      wing dural arteriovenous fistula (dAVF) are rare. These lesions usually result
      from traumatic brain injury, and associated with skull fracture. In this paper,
      the authors report a case of a patient with a ruptured traumatic pseudoaneurysm
      of MMA and medial sphenoid wing dAVF presented with an intracerebral hemorrhage
      in the left temporal region and subarachnoid hemorrhage. These lesions were
      completely obliterated by endovascular treatment, and the patient was recovered
      without any neurologic deficit. However, 18-day after the procedure, delayed
      neurologic deficits were developed due to cerebral vasospasm.

PMID- 29201855
TI  - Posterior Reversible Encephalopathy Syndrome after Head Trauma Surgery in
      Pediatric Patient without Any Underlying Disease.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder
      characterized by signs of posterior cerebral edema upon radiographic examination.
      A 16-year-old girl was involved in motorcycle accident and depressed frontal
      fracture was presented. She had generalized seizures 3 days after dural repair
      and fracture reduction. Signal changes was noted on both parietal lobes in the
      magnetic resonance images and it was completely resolved in 3 months follow-up.
      We would like to present the case that demonstrated PRES related hypertension
      after head trauma surgery for cerebrospinal fluid leakage in pediatric patient
      without any underlying disease.

PMID- 29201856
TI  - Complete Reversal of Diffusion Restriction after Treatment of Traumatic Carotid
      Cavernous Fistula.
AB  - A 15-year-old man presented with stupor following a motorcycle traffic accident.
      The patient was diagnosed with a traumatic left carotid cavernous fistula (CCF)
      with pseudoaneurysm of the left internal carotid artery. Brain magnetic resonance
      imaging (MRI) showed transiently restricted diffusion in the left centrum
      semiovale white matter and lower temporo-occipital area extending to the splenium
      of the corpus callosum, with high signal intensity on diffusion-weighted imaging.
      On the 35th day of admission, the patient had complete neurological recovery and
      a follow-up brain MRI revealed complete resolution of the lesions in the left
      centrum semiovale and splenium of the corpus callosum. These clinical and
      radiological features are highly suggestive of complete reversal of diffusion
      restriction after successful embolization of traumatic CCF.

PMID- 29201857
TI  - A Rare Complication of Lumbar Spinal Surgery: Pneumocephalus.
AB  - A 25-year-old male patient with severe thigh and right side pain was presented.
      In the lumbar magnetic resonance images, there was a contrasting spinal cord
      tumor image with 1 cm in diameter at the level of the L3 vertebra. The patient
      was operated and the tumor was totally removed. All the pain of the patient
      recovered. The patient's postoperative two days were very comfortable and the
      patient was early mobilized. On the third postoperative day, the patient
      complained of severe headache, nausea and vomiting. Immediate cranial computed
      tomography (CT) images was performed. Cerebral pneumocephalus was present in CT.
      The patient was treated with definite bed rest and plenty of fluid replacement.
      After three days, the patient's complaints were completely improved. This
      improvement was confirmed by performing a cerebral CT scan. In the formation of
      pneumocephalus, air is compressed into the intradural space during operation and
      this passes to the cerebral space. Definite bed rest, abundant fluid replacement
      and, in addition, highly inspired oxygen therapy are sufficient to correct the
      condition.

PMID- 29201858
TI  - Thoracolumbar Paraspinal Myonecrosis after Aortic Dissection.
AB  - Thoracolumbar paraspinal myonecrosis can be developed with various etiologies. It
      can induce compartment syndrome of spinal muscles and cause elevated pressure on
      back muscles, resulting in severe back pain. Thoracolumbar paraspinal myonecrosis
      is a very rare disease. There are only a few studies about paraspinal
      myonecrosis. Here we report a case of a spontaneous thoracolumbar paraspinal
      myonecrosis in a patient who had asymptomatic abdominal aortic dissection.
      Through this case, etiologies, clinical features, radiologic findings, and
      treatment options for thoracolumbar paraspinal myonecrosis are discussed.

PMID- 29201859
TI  - Predictable, Tunable Protein Production in Salmonella for Studying Host-Pathogen
      Interactions.
AB  - Here we describe the use of synthetic genetic elements to improve the
      predictability and tunability of episomal protein production in Salmonella. We
      used a multi-pronged approach, in which a series of variable-strength synthetic
      promoters were combined with a synthetic transcriptional terminator, and plasmid
      copy number variation. This yielded a series of plasmids that drive uniform
      production of fluorescent and endogenous proteins, over a wide dynamic range. We
      describe several examples where this system is used to fine-tune constitutive
      expression in Salmonella, providing an efficient means to titrate out toxic
      effects of protein production.

PMID- 29201861
TI  - Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and
      experimental approach.
AB  - Background: We had earlier reported that the extract of Pueraria tuberosa
      significantly inhibits DPP-IV enzyme, resulting in glucose tolerance response in
      rats. In this study, we have explored the active phytochemicals responsible for
      this potential. The results have been validated in both fasting and postprandial
      states in the plasma of normal rats and also in fasting blood and intestinal
      homogenates of diabetic models. Methods: Pueraria tuberosa water extract (PTWE)
      was administered to normal Charles Foster rats for 35 days and to diabetic model
      (65 mg/kg bw) for 10 days. After treatments, oral glucose tolerance test (OGTT)
      and insulin was done for 90 min, and the changes in the levels of GLP-1, GIP, and
      DPP-IV activities were monitored in fasting and postprandial states. In the case
      of the diabetic model, DPP-IV activity was measured in intestinal homogenate and
      basal insulin in plasma. The components of PTWE were analyzed via HPLC-MS based
      on their chemical formula, molecular mass, and retention time. Using the
      molecular docking study, we have selected the top five components having strong
      binding energy with DPP-IV. Results: The increase in secretion of GLP-1 and GIP
      was significantly higher in the postprandial state when compared to fasting
      condition. GLP-1 plasma concentration increased by 5.8 and 2.9 folds and GIP
      increased by 8.7 and 2.4 folds in PTWE and control rats, respectively. In
      contrast, the postprandial decrease in DPP-IV specific activities was recorded at
      2.3 and 1.4 folds. The response in OGTT and insulin was also consistent with
      these changes. In comparison to diabetic controls, PTWE-administered rats showed
      decreased DPP-IV activity in the intestine, leading to enhanced basal insulin
      concentration. Through molecular docking, we found Puerarone and Robinin to be
      the most potential phytochemicals of PTWE for DPP-IV inhibition. Binding energy
      (kcal/mol) and dissociation constant (pM) of Robinin with DPP-IV protein were
      found to be 7.543 and 2,957,383.75, respectively. For Puerarone, it was 7.376 and
      3,920,309, respectively. Conclusions: Thus, this study provides the novel active
      components that contribute to the DPP-IV inhibitory property of PTWE.

PMID- 29201860
TI  - Modulating Host Signaling Pathways to Promote Resistance to Infection by Candida
      albicans.
AB  - Candida albicans is a common human fungal pathogen capable of causing serious
      systemic infections that can progress to become lethal. Current therapeutic
      approaches have limited effectiveness, especially once a systemic infection is
      established, in part due to the lack of an effective immune response. Boosting
      the immune response to C. albicans has been the goal of immunotherapy, but it has
      to be done selectively to prevent deleterious hyperinflammation (sepsis).
      Although an efficient inflammatory response is necessary to fight infection, the
      typical response to C. albicans results in collateral damage to tissues thereby
      exacerbating the pathological effects of infection. For this reason, identifying
      specific ways of modulating the immune system holds promise for development of
      new improved therapeutic approaches. This review will focus on recent studies
      that provide insight using mutant strains of mice that are more resistant to
      bloodstream infection by C. albicans. These mice are deficient in signal
      transduction proteins including the Jnk1 MAP kinase, the Cbl-b E3 ubiquitin
      ligase, or the Sts phosphatases. Interestingly, the mutant mice display a
      different response to C. albicans that results in faster clearance of infection
      without hyper-inflammation and collateral damage. A common underlying theme
      between the resistant mouse strains is loss of negative regulatory proteins that
      are known to restrain activation of cell surface receptor-initiated signaling
      cascades. Understanding the cellular and molecular mechanisms that promote
      resistance to C. albicans in mice will help to identify new approaches for
      improving antifungal therapy.

PMID- 29201863
TI  - Predictive Assessment of Cancer Center Catchment Area from Electronic Health
      Records.
AB  - Healthcare facilities (HF) may identify catchment areas (CA) by selecting
      criteria that depend on various factors. These refer to hospital activities,
      geographical definition, patient covariates, and more. The analyses that were
      traditionally pursued have a limiting factor in the consideration of only static
      conditions. Instead, some of the CA determinants involve influences occurring at
      both temporal and spatial scales. The study of CA in the cancer context means
      choosing between HF, usually divided into general hospitals versus oncological
      centers (OCs). In the CA context, electronic health records (EHRs) promise to be
      a valuable source of information, one driving the next-generation patient-driven
      clinical decision support systems. Among the challenges, digital health requires
      the re-definition of a role of stochastic modeling to deal with emerging
      complexities from data heterogeneity. To model CA with cancer EHR, we have chosen
      a computational framework centered on a logistic model, as a reference, and on a
      multivariate statistical approach. We also provided a battery of tests for CA
      assessment. Our results indicate that a more refined CA model's structure yields
      superior discrimination power between health facilities. The increased
      significance was also visualized by comparative evaluations with ad hoc geo
      localized maps. Notably, a cancer-specific spatial effect can be noticed,
      especially for breast cancer and through OCs. To mitigate the data distributional
      influences, bootstrap analysis was performed, and gains in some cancer-specific
      and spatially concentrated regions were obtained. Finally, when the temporal
      dynamics are assessed along a 3-year timeframe, negligible differential effects
      appear between predicted probabilities observed between standard critical values
      and bootstrapped values. In conclusion, for interpreting CA in terms of both
      spatial and temporal dynamics, sophisticated models are required. The one here
      proposed suggests that bootstrap can improve test accuracy. We recommend that
      evidences from stochastic modeling are merged with visual analytics, as this
      combination may be exploited by policy-makers in support to quantitative CA
      assessment.

PMID- 29201862
TI  - The Influence of Different Caregivers on Infant Growth and Development in China.
AB  - Objective: An increasing number of parents in China ask grandparents or
      babysitters to care for their children. Modern parents are often the only child
      in their family because of China's One-Child Policy and thus may lack interaction
      with siblings. Accordingly, the present study aimed to explore whether different
      caregivers affect the physical and development of infants in China. Methods: In
      total, 2,514 infants were enrolled in our study. We assessed their weight-for
      age, supine length-for-age, weight-for-length, occipital-frontal circumference,
      and Denver Developmental Screening Test (DDST) results and recorded their general
      parental information and their primary caregivers. Results: The weights and
      lengths of 12-month-old infants under the care of babysitters were significantly
      lower than those of infants under the care of parents or grandparents (P < 0.05).
      Additionally, 12-month-old infants under the care of babysitters had the lowest
      DDST pass rate (75%) among the three groups (chi2 = 11.819, P = 0.012),
      especially for the fine motor-adaptive and language domains. Compared to 12-month
      old infants under the care of parents and babysitters, infants under the care of
      grandparents were more likely to be overweight or obese (P < 0.001). Conclusion:
      The study showed that caregivers had a dominant role in the physical and
      cognitive development of the infants. Specifically, compared with infants raised
      by grandparents and parents, 12-month-old infants under the care of babysitters
      had partially suppressed lengths and weights and lagged cognitively. The 12-month
      old infants under the care of grandparents were more overweight than those cared
      for by parents and babysitters.

PMID- 29201865
TI  - An Inexpensive High-Temporal Resolution Electronic Sun Journal for Monitoring
      Personal Day to Day Sun Exposure Patterns.
AB  - Exposure to natural sunlight, specifically solar ultraviolet (UV) radiation
      contributes to lifetime risks of skin cancer, eye disease, and diseases
      associated with vitamin D insufficiency. Improved knowledge of personal sun
      exposure patterns can inform public health policy; and help target high-risk
      population groups. Subsequently, an extensive number of studies have been
      conducted to measure personal solar UV exposure in a variety of settings. Many of
      these studies, however, use digital or paper-based journals (self-reported
      volunteer recall), or employ cost prohibitive electronic UV dosimeters (that
      limit the size of sample populations), to estimate periods of exposure. A cost
      effective personal electronic sun journal (ESJ) built from readily available
      infrared photodiodes is presented in this research. The ESJ can be used to
      complement traditional UV dosimeters that measure total biologically effective
      exposure by providing a time-stamped sun exposure record. The ESJ can be easily
      attached to clothing and data logged to personal devices (including fitness
      monitors or smartphones). The ESJ improves upon self-reported exposure recording
      and is a cost effective high-temporal resolution option for monitoring personal
      sun exposure behavior in large population studies.

PMID- 29201864
TI  - A Review of the Mycotoxin Enniatin B.
AB  - Mycotoxin enniatin B (ENN B) is a secondary metabolism product by Fusarium fungi.
      It is a well-known antibacterial, antihelmintic, antifungal, herbicidal, and
      insecticidal compound. It has been found as a contaminant in several food
      commodities, particularly in cereal grains, co-occurring also with other
      mycotoxins. The primary mechanism of action of ENN B is mainly due to its
      ionophoric characteristics, but the exact mechanism is still unclear. In the last
      two decades, it has been a topic of great interest since its potent mammalian
      cytotoxic activity was demonstrated in several mammalian cell lines. Moreover,
      the co-exposure in vitro with other mycotoxins enhances its toxic potential
      through synergic effects, depending on the concentrations tested. Despite its
      clear cytotoxic effect, European Food Safety Authority stated that acute exposure
      to ENNs, such as ENN B, does not indicate concern for human health, but a concern
      might be the chronic exposure. However, given the lack of relevant toxicity data,
      no firm conclusion could be drawn and a risk assessment was not possible. In
      fact, very few studies have been carried out in vivo and, in these studies, no
      adverse effects were observed. So, research on toxicological effects induced by
      ENN B is still on-going. Recently, some studies are dealing with new advances
      regarding ENN B. This review summarizes the information on biochemical and
      biological activity of ENN B, focusing on toxicological aspects and on the latest
      advances in research on ENN B.

PMID- 29201866
TI  - Getting Lost Behavior in Patients with Mild Alzheimer's Disease: A Cognitive and
      Anatomical Model.
AB  - Background: Getting lost behavior (GLB) in the elderly is believed to involve
      poor top-down modulation of visuospatial processing, by impaired executive
      functions. However, since healthy elderly and elderly with Alzheimer's disease
      (AD) experience a different pattern of cognitive decline, it remains unclear
      whether this hypothesis can explain GLB in dementia. Objective: We sought to
      identify whether poor executive functions and working memory modulate the
      relationship between visuospatial processing and prevalence of GLB in healthy
      elderly and patients with AD. Complementary to this, we explored whether brain
      regions critical for executive functions modulate the relationship between GLB
      and brain regions critical for visuospatial processing. Method: Ninety-two
      participants with mild AD and 46 healthy age-matched controls underwent
      neuropsychological assessment and a structural MRI. GLB was assessed using a
      semistructured clinical interview. Path analysis was used to explore interactions
      between visuospatial deficits, executive dysfunction/working memory, and
      prevalence of GLB, in AD and controls independently. Results: For both healthy
      controls and patients with mild AD, visuospatial processing deficits were
      associated with GLB only in the presence of poor working memory. Anatomically,
      GLB was associated with medial temporal atrophy in patients with mild AD, which
      was not strengthened by low frontal gray matter (GM) volume as predicted.
      Instead, medial temporal atrophy was more strongly related to GLB in patients
      with high frontal GM volumes. For controls, GLB was not associated with
      occipital, parietal, medial temporal, or frontal GM volume. Conclusion:
      Cognitively, a top-down modulation deficit may drive GLB in both healthy elderly
      and patients with mild AD. This modulation effect may be localized in the medial
      temporal lobe for patients with mild AD. Thus, anatomical substrates of GLB in
      mild AD may not follow the typical top-down modulation mechanisms often reported
      in the healthy aging population. Implications advance therapeutic practices by
      highlighting the need to target both working memory and visuospatial deficits
      simultaneously, and that anatomical substrates of GLB may be disease specific.

PMID- 29201867
TI  - Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer.
AB  - Inhibiting DNA synthesis is an important therapeutic strategy that is widely used
      to treat a number of hyperproliferative diseases including viral infections,
      autoimmune disorders, and cancer. This chapter describes two major categories of
      therapeutic agents used to inhibit DNA synthesis. The first category includes
      purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase
      activity. The second category includes DNA damaging agents including cisplatin
      and chlorambucil that modify the composition and structure of the nucleic acid
      substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on
      describing the molecular mechanisms of these inhibitory effects against
      chromosomal and mitochondrial DNA polymerases. Discussions are also provided on
      the mechanisms associated with resistance to these therapeutic agents. A primary
      focus is toward understanding the roles of specialized DNA polymerases that by
      pass DNA lesions produced by DNA damaging agents. Finally, a section is provided
      that describes emerging areas in developing new therapeutic strategies targeting
      specialized DNA polymerases.

PMID- 29201869
TI  - A Knot Polynomial Invariant for Analysis of Topology of RNA Stems and Protein
      Disulfide Bonds.
AB  - Knot polynomials have been used to detect and classify knots in biomolecules.
      Computation of knot polynomials in DNA and protein molecules have revealed the
      existence of knotted structures, and provided important insight into their
      topological structures. However, conventional knot polynomials are not well
      suited to study RNA molecules, as RNA structures are determined by stem regions
      which are not taken into account in conventional knot polynomials. In this study,
      we develop a new class of knot polynomials specifically designed to study RNA
      molecules, which considers stem regions. We demonstrate that our knot polynomials
      have direct structural relation with RNA molecules, and can be used to classify
      the topology of RNA secondary structures. Furthermore, we point out that these
      knot polynomials can be used to model the topological effects of disulfide bonds
      in protein molecules.

PMID- 29201868
TI  - The Scope of Big Data in One Medicine: Unprecedented Opportunities and
      Challenges.
AB  - Advances in high-throughput molecular biology and electronic health records
      (EHR), coupled with increasing computer capabilities have resulted in an
      increased interest in the use of big data in health care. Big data require
      collection and analysis of data at an unprecedented scale and represents a
      paradigm shift in health care, offering (1) the capacity to generate new
      knowledge more quickly than traditional scientific approaches; (2) unbiased
      collection and analysis of data; and (3) a holistic understanding of biology and
      pathophysiology. Big data promises more personalized and precision medicine for
      patients with improved accuracy and earlier diagnosis, and therapy tailored to an
      individual's unique combination of genes, environmental risk, and precise disease
      phenotype. This promise comes from data collected from numerous sources, ranging
      from molecules to cells, to tissues, to individuals and populations-and the
      integration of these data into networks that improve understanding of heath and
      disease. Big data-driven science should play a role in propelling comparative
      medicine and "one medicine" (i.e., the shared physiology, pathophysiology, and
      disease risk factors across species) forward. Merging of data from EHR across
      institutions will give access to patient data on a scale previously unimaginable,
      allowing for precise phenotype definition and objective evaluation of risk
      factors and response to therapy. High-throughput molecular data will give insight
      into previously unexplored molecular pathophysiology and disease etiology.
      Investigation and integration of big data from a variety of sources will result
      in stronger parallels drawn at the molecular level between human and animal
      disease, allow for predictive modeling of infectious disease and identification
      of key areas of intervention, and facilitate step-changes in our understanding of
      disease that can make a substantial impact on animal and human health. However,
      the use of big data comes with significant challenges. Here we explore the scope
      of "big data," including its opportunities, its limitations, and what is needed
      capitalize on big data in one medicine.

PMID- 29201870
TI  - Factors that influence blood loss and need for transfusion following total knee
      arthroplasty.
AB  - Background: Blood loss during total knee arthroplasty (TKA) remains a concern, as
      many patients require blood transfusions, which increase risks of allergic
      reactions, disease transmission, and thromboembolisms. The purpose was to
      determine factors associated with blood loss and need for transfusion in patients
      receiving routine TKA. Methods: The authors prospectively analyzed 150
      consecutive uncemented TKAs for age, gender, body mass index (BMI), anticoagulant
      medication, type of anesthesia, tranexamic acid (TXA) administration, tourniquet
      inflation, drain placement, pre- and post-operative Haemoglobin (Hb) level
      (g/dL), and whether transfusion was necessary. Univariable and multivariable
      regression analyses were performed to identify factors associated with Hb loss
      and need for transfusion with significance level set at P value<0.05. Results:
      The cohort comprised 92 women and 58 men, aged 69.5+/-8.9 years. The mean Hb loss
      was 3.7+/-1.3 g/dL. The 20 patients (13%) who had transfusions also had lower
      preoperative Hb (12.6+/-1.2 g/dL) compared to the remaining patients (14.3+/-1.2
      g/dL). Hb loss was significantly associated with preoperative Hb, TXA, and
      gender, but multivariable regression identified gender as a confounder and
      indicated that TXA reduced Hb loss by 0.92 g/dL. Multivariable regression
      revealed the need for transfusion was only significantly associated with
      preoperative Hb and indicated that a decrease of preoperative Hb by 1 g/dL nearly
      quadrupled the chances of needing transfusion. Conclusions: Hb loss was
      significantly associated with preoperative Hb levels and use of TXA, while the
      need for transfusion was only associated with preoperative Hb levels. These
      findings could help identify patients at risk for blood transfusions. Level of
      evidence: level III, prospective case series.

PMID- 29201872
TI  - Establishing an evaluation mode with multiple primary outcomes based on
      combination of diseases and symptoms in TCM clinical trials.
AB  - The development of a scientific evaluation tool is a prerequisite to reflect the
      efficacy of traditional Chinese medicine (TCM). At present, separate analysis of
      each outcome is the most commonly used method in randomized controlled trials
      (RCTs) of TCM, while this method has been reported to have some limitations.
      Combination evaluation of multiple primary outcomes including diseases and
      symptoms can reflect the efficacy of TCM comprehensively and objectively. Now,
      several multivariate statistical methods have been proposed to analyze RCTs with
      multiple clinical outcomes. In this article, we highlighted the two commonly used
      methods, global statistical test (GST) methodology and alpha-adjustment
      procedures, and introduced an evaluation mode. First, we used one stage adaptive
      adjustment strategy to estimate the correlation among multiple primary outcomes
      in blindness, which can resolve the inappropriate correlation estimation among
      multiple primary outcomes, then we introduced an adaptation of the Bonferroni
      procedure which can account for correlated data to calculate the alpha of
      individual outcome. GST using O'Brien ranking procedure and the corresponding
      global treatment effect (GTE) measure were used to assess the treatment's global
      impact. We will conduct a randomized, double-blind, controlled trial with
      compound Danshen dripping pills for stable angina to explore establishing the
      evaluation mode. We hope that the introduction of this approach can provide
      methodological aid for the assessment of therapeutic effect of TCM.

PMID- 29201871
TI  - Calcitonin gene-related peptide: neuroendocrine communication between the
      pancreas, gut, and brain in regulation of blood glucose.
AB  - Background: Calcitonin gene-related peptide (CGRP), a ubiquitous neuropeptide,
      plays a diverse and intricate role in chronic low-grade inflammation, including
      conditions such as obesity, type 2 diabetes, and diabetes of the exocrine
      pancreas. Diabetes of exocrine pancreas is characterised by chronic hyperglycemia
      and is associated with persistent low-grade inflammation and altered secretion of
      certain pancreatic and gut hormones. While CGRP may regulate glucose homeostasis
      and the secretion of pancreatic and gut hormones, its role in chronic
      hyperglycemia after acute pancreatitis (CHAP) is not known. The aim of this study
      was to investigate the association between CGRP and CHAP. Methods: Fasting blood
      samples were collected to measure insulin, HbA1c, CGRP, amylin, C-peptide,
      glucagon, pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide,
      glicentin, glucagon-like peptide-1 and 2, and oxyntomodulin. Modified Poisson
      regression analysis and linear regression analyses were conducted. Five
      statistical models were used to adjust for demographic, metabolic, and
      pancreatitis-related risk factors. Results: A total of 83 patients were
      recruited. CGRP was significantly associated with CHAP in all five models (P
      trend <0.005). Further, it was significantly associated with oxyntomodulin
      (P<0.005) and glucagon (P<0.030). Oxyntomodulin and glucagon independently
      contributed 9.7% and 7%, respectively, to circulating CGRP variance. Other
      pancreatic and gut hormones were not significantly associated with CGRP.
      Conclusions: CGRP is involved in regulation of blood glucose in individuals after
      acute pancreatitis. This may have translational implications in prevention and
      treatment of diabetes of the exocrine pancreas.

PMID- 29201873
TI  - An innovative robotic platform for magnetically-driven painless colonoscopy.
AB  - Colorectal cancer (CRC) represents a significant medical threat with a dramatic
      impact on the healthcare system with around 1.3 million patients worldwide,
      causing more than 700 thousand deaths annually. A key-aspect to successful and
      cost-effective disease management is represented by the early detection of CRC at
      asymptomatic stage. For this reason, population screening is highly recommended
      for patients older than 50 years or at high risk for familiarity. Currently, the
      standard endoscopic techniques do not meet this need. In recent years, innovative
      endoscopic robotic techniques and active locomotion devices have been developed
      as alternatives to conventional colonoscopy. The magnetically-driven robotic
      platform, presented by the authors, is conceived to perform less invasive and
      more comfortable colonoscopy with the aim to promote screening campaigns for
      detection of early colorectal neoplasm.

PMID- 29201874
TI  - A global perspective on capsule endoscopy.
AB  - A search of the internet today to quantify the estimated value of capsules from a
      global perspective, easily delivers figures stating around $200 million in 2014
      to about $400 million by 2020, which would be approximately 10% of the
      gastrointestinal endoscopic market. Is this a steep rise within just six years or
      could the capsule market do even better? What chances does this offer and what
      are the key aspects for future success? By 2020, more than 1 billion people are
      aged sixty or older and around one third of them will live in what the UN calls
      "more developed regions". Naturally, this brings an increased demand for
      colorectal cancer screening and surgery. But keeping in mind that basically every
      healthcare system, in any country, is already operating at its limits, how do we
      secure future treatment for a growing community? Surely more competition will
      steadily bring down prices for capsules. However, that does not ease the amount
      of time that is spent to properly read any video and issue a valid diagnosis for
      every patient. This article intends to give an overview about the current global
      market for capsule endoscopy (CE) with a perspective on typical patients, their
      indications, and how the capsules are used and by whom. Further aspects, such as
      standardization of training, reading and future trends will also be elaborated
      on.

PMID- 29201875
TI  - Surgical treatment of synchronous multiple neuroendocrine lung tumours (case
      series): is more always better?
AB  - Pulmonary neuroendocrine lung tumours are uncommon neoplasm; the presence of
      multiple and synchronous lesions is rare, and few case report are described in
      the literature. We present a case series of three patients without particular
      symptom and radiologic finding of multiple synchronous pulmonary nodules. All the
      patients underwent surgical treatment; histopathologic examination revealed
      typical carcinoid tumours in all three cases (one patient has a synchronous
      atypical carcinoid). No oncological progressions were observed at follow-up. A
      review of current literature is also presented with a suggested strategy
      management.

PMID- 29201876
TI  - EGFR mutation positive non-small cell lung cancer: can we identify predictors of
      benefit from immune checkpoint inhibitors.

PMID- 29201877
TI  - Eravacycline for treatment of complicated intra-abdominal infections: the fire is
      not ignited!

PMID- 29201879
TI  - Treatment recommendations by clinicians in stage I non-small cell lung cancer:
      better work-up leads to less discussion.

PMID- 29201878
TI  - Radiotherapy treatment strategies for squamous cell carcinoma of the cervical
      oesophagus: moving toward better outcomes.

PMID- 29201880
TI  - Towards a comprehensive framework for cell-free DNA analysis: lessons from
      TRACERx.

PMID- 29201881
TI  - Fasting and engineered diets as powerful tool in the medical practice: an old
      approach in the new era.

PMID- 29201882
TI  - Remote home monitoring to identify and prevent diabetic foot ulceration.

PMID- 29201883
TI  - The role of foot collateral vessels on angiosome-oriented revascularization.

PMID- 29201884
TI  - Increased cancer-specific mortality in individuals developing mental disorders
      after cancer diagnosis: biomedical factors versus psychosocial support.

PMID- 29201885
TI  - Alectinib can replace crizotinib as standard first-line therapy for ALK-positive
      lung cancer.

PMID- 29201886
TI  - Very early antiretroviral therapy permits CD8 T cells to keep HIV reservoirs at
      bay.

PMID- 29201887
TI  - The evidence system of traditional Chinese medicine based on the Grades of
      Recommendations Assessment, Development and Evaluation framework.

PMID- 29201888
TI  - Development of scoring system for risk stratification in clinical medicine: a
      step-by-step tutorial.
AB  - Risk scores play an important role in clinical medicine. With advances in
      information technology and availability of electronic healthcare record, scoring
      systems of less commonly seen diseases and population can be developed. The aim
      of the article is to provide a tutorial on how to develop and validate risk
      scores based on a virtual dataset by using R software. The dataset we generated
      including numeric and categorical variables and firstly the numeric variables
      would be converted to factor variables according to cutoff points identified by
      the LOESS smoother. Then risk points of each variable, which are related to the
      coefficients in logistic regression, are assigned to each level of the converted
      factor variables and other categorical variables. Finally, the total score is
      calculated for each subject to represent the prediction of the outcome event
      probability. The original dataset is split into training and validation subsets.
      Discrimination and calibration are evaluated in the validation subset. R codes
      with explanations are presented in the main text.

PMID- 29201889
TI  - Treating our patients with compassion & respect: interview with Dr. Zhaolin Lu of
      the Department of Endocrinology of Peking Union Medical College Hospital.

PMID- 29201890
TI  - Pareidolias in idiopathic RBD-an author response letter to the Editorial "What
      the 'man in the moon' can tell us about the future of our brains".

PMID- 29201891
TI  - Morbidity, mortality, and obesity paradox.

PMID- 29201892
TI  - Comment on "Mobile phone radiofrequency exposure has no effect on DNA double
      strand breaks (DSB) in human lymphocytes".

PMID- 29201893
TI  - Evidence of the Complexity of Gene Expression Analysis in Fish Wild Populations.
AB  - The present work examines the induction of the band 3 anion transport protein,
      mitogen-activated protein kinase, and lactate dehydrogenase, respectively related
      to osmolyte transport, cell volume regulation, and energy production in the gills
      of two tilapia strains exposed to either freshwater or hypersaline water.
      Overall, genes showed similar expression patterns between strains. However, a
      wild population survey across a range of natural habitats and salinities did not
      reveal the expected patterns. Although significant, the correlations between gene
      expression and salinity were slightly ambiguous and did not show any link with
      phenotypic differences in life history traits previously reported between the
      same populations. The differential expression was also not associated with the
      population genetic structure inferred from neutral markers. The results suggest
      that the differential expression observed is not the result of evolutionary
      forces such as genetic drift or adaptation by natural selection. Instead, it can
      be speculated that genes responded to various abiotic and biotic stressors,
      including factors intrinsic to animals. This study provides clear evidence of the
      complexity of gene expression analysis in wild populations and shows that more
      attention needs to be paid when selecting candidates as potential biomarkers for
      monitoring adaptive responses to a specific environmental perturbation.

PMID- 29201894
TI  - Genetics of Marbling in Wagyu Revealed by the Melting Temperature of
      Intramuscular and Subcutaneous Lipids.
AB  - Extreme marbling or intramuscular deposition of lipid is associated with Wagyu
      breeds and is therefore assumed to be largely inherited. However, even within
      100% full blood Wagyu prepared under standard conditions, there is unpredictable
      scatter of the degree of marbling. Here, we evaluate melting temperature (Tm ) of
      intramuscular fat as an alternative to visual scores of marbling. We show that
      "long fed" Wagyu generally has Tm below body temperature but with a considerable
      range under standardized conditions. Individual sires have a major impact
      indicating that the variation is genetic rather than environmental or random
      error. In order to measure differences of lower marbling breeds and at shorter
      feeding periods, we have compared Tm in subcutaneous fat samples from over the
      striploin. Supplementary feeding for 100 to 150 days leads to a rapid decrease in
      Tm of 50% Red Wagyu (Akaushi) : 50% European crosses, when compared to 100%
      European. This improvement indicates that the genetic effect of Wagyu is useful,
      predictable, and highly penetrant. Contemporaneous DNA extraction does not affect
      the measurement of Tm . Thus, provenance can be traced and substitution can be
      eliminated in a simple and cost-effective manner.

PMID- 29201895
TI  - Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential.
AB  - The present paper investigated the efficiency of Urtica dioica (U. dioica) on
      hemostatic and wound healing activities. U. dioica leaf extracts were evaluated
      for their antibacterial and antioxidant effects as well as their flavonoid and
      polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most
      potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid
      and polyphenol richness, was selected for hemostatic and wound healing
      evaluation. Twenty-four rats completing full-thickness wounds were split into
      four groups. The wounds were topically treated with saline solution, glycerol,
      "CICAFLORA," and U. dioica EtOH-H2OE (50 uL/mm2) until day 11. The wound healing
      effect was assessed by macroscopic, histological, and biochemical parameters.
      Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the
      control animals (60.91%) on the 11th day of wounding (P < 0.01).
      Histopathological and biochemical explorations showed full epidermal regeneration
      and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE
      treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of
      unsaturated fatty acids and a high concentration of lupeol known for their
      involvement in reepithelialization. These results prove the efficiency of U.
      dioica EtOH-H2OE in wound healing and supported its traditional use.

PMID- 29201896
TI  - Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of
      Postischemic Intestinal Mucosa.
AB  - Background: Intestinal ischemia is often caused by a malperfusion of the upper
      mesenteric artery. Since the intestinal mucosa is one of the most rapidly
      proliferating organs in human body, this tissue can partly regenerate itself
      after the onset of ischemia and reperfusion (I/R). Therefore, we investigated
      whether glycine, sodium pyruvate, and resveratrol can either support or
      potentially harm regeneration when applied therapeutically after reperfusion
      injury. Methods: I/R of the small intestine was initiated by occluding and
      reopening the upper mesenteric artery in rats. After 60 min of ischemia and 300
      min of reperfusion, glycine, sodium pyruvate, or resveratrol was administered
      intravenously. Small intestine regeneration was analyzed regarding tissue damage,
      activity of saccharase, and Ki-67 positive cells. Additionally, systemic
      parameters and metabolic ones were obtained at selected periods. Results:
      Resveratrol failed in improving the outcome after I/R, while glycine showed a
      partial beneficial effect. Sodium pyruvate ameliorated metabolic acidosis,
      diminished histopathologic tissue injury, and increased cell proliferation in the
      small intestine. Conclusion: While glycine could improve in part regeneration but
      not proliferation, sodium pyruvate seems to be a possible therapeutic agent to
      facilitate proliferation and to support mucosal regeneration after I/R injury to
      the small intestine.

PMID- 29201897
TI  - Combined Treatment with an Anticoagulant and a Vasodilator Prevents Steroid
      Associated Osteonecrosis of Rabbit Femoral Heads by Improving Hypercoagulability.
AB  - Steroid-associated osteonecrosis of the femoral head remains a challenging
      problem in orthopedics worldwide. One pathomechanism is ischemia of the femoral
      head, as a result of thrombus formation and vasoconstriction. The present study
      investigates the effects of combination prevention with enoxaparin and EGb 761 on
      steroid-associated ONFH in rabbits. Rabbits were randomly divided into 5 groups
      (control group, model group, enoxaparin group, ginkgo group, and combination
      group). With the exception of the control group, the groups of rabbits were
      modeled with lipopolysaccharide and methylprednisolone acetate. Starting with
      modeling, the enoxaparin group and ginkgo group were injected with 1 MUg/kg/day
      enoxaparin subcutaneously and orally given 40 mg/kg/day EGb 761 for 4 weeks,
      respectively; the combination group received both treatments. After modeling for
      6 weeks, the hematology data indicated prolonged PT and APTT in the three
      prevention groups. The micro-CT examination revealed higher bone density and
      better structure; histomorphometry revealed significant pathological changes.
      Immunohistochemistry revealed higher expression of BMP-2 and VEGF, thus revealing
      better osteogenesis and angiogenesis activities. Among the three prevention
      groups, the combination group had the most efficient results. In conclusion, the
      combined prevention with an anticoagulant and a vasodilator has the potential to
      decrease the incidence of steroid-associated ONFH in rabbits.

PMID- 29201898
TI  - Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by
      Modulating Multiple Cell Cycle Regulators.
AB  - Platelets (PLTs) are produced by megakaryocytes (MKs) that completed
      differentiation and endomitosis. Endomitosis is an important process in which the
      cell replicates its DNA without cytokinesis and develops highly polyploid MK. In
      this study, to gain a better PLTs production, four small molecules (Rho-Rock
      inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor
      (ABI)) and their combinations were surveyed as MK culture supplements for
      promoting polyploidization. Three leukemia cell lines as well as primary
      mononuclear cells were chosen in the function and mechanism studies of the small
      molecules. In an optimal culture method, cells were treated with different small
      molecules and their combinations. The impact of the small molecules on
      megakaryocytic surface marker expression, polyploidy, proliferation, and
      apoptosis was examined for the best MK polyploidization supplement. The elaborate
      analysis confirmed that the combination of SI and RRI together with our MK
      induction system might result in efficient ploidy promotion. Our experiments
      demonstrated that, besides direct downregulation on the expression of
      cytoskeleton protein actin, SI and RRI could significantly enhance the level of
      cyclins through the suppression of p53 and p21. The verified small molecule
      combination might be further used in the in vitro PLT manufacture and clinical
      applications.

PMID- 29201899
TI  - Cephalometric Soft Tissue Characteristics of Unilateral Cleft Lip and Palate
      Patients in Relation to Missing Teeth.
AB  - Objective: This study aimed to evaluate cephalometric soft tissue characteristics
      in individuals with unilateral complete cleft lip and palate (UCCLP) both with
      and without missing teeth. Design: A retrospective investigation of patient
      records, who are being treated at the cleft lip and palate (CLP) clinics at the
      College of Dentistry. Ninety-six consecutive records of nonsyndromic UCCLP
      subjects were recruited (33 subjects without missing teeth and 63 subjects with
      missing teeth). Linear and angular soft tissue measurements obtained from lateral
      cephalometric radiographs were evaluated and compared among the studied samples.
      Results: Lower lip was significantly retruded and shorter (p = 0.037), p = 0.015,
      respectively; in addition to the fact that shallower mentolabial sulcus (p =
      0.05) was found in the subjects with missing teeth, the rest of the soft tissue
      was not significantly different between the two groups. Conclusion: In subjects
      with a UCCLP anomaly, missing teeth have an effect on lower lip position and
      length, which influenced the mentolabial sulcus. Lower lip position and length
      differ between cleft patients who present with either multiple missing teeth or
      with no missing teeth, and this needs to be considered during orthodontic
      treatment planning and surgical management for the cleft defect.

PMID- 29201900
TI  - Abdominal Wall Reconstruction after Flap Surgery and the Effect on the Immune
      System.
AB  - Background: The aim of our study was to investigate the impact of abdominal wall
      reconstruction surgery on tissue anatomy and to explore how flap surgery
      influences the patient's immune status. Methods: Experimental abdominal wall
      defects were created in 8 Sus scrofa (swine) animal models. The animals were
      divided into two groups: 4 swine were euthanized one month after surgery for the
      biopsies retrieval purpose and the other 4 swine were kept alive and the
      collection of blood samples has been done 6 months after surgery. In order to
      evaluate the relative gene expression in operated-on animal cohorts we compared
      them with samples from 4 healthy swine used as controls. Results: The
      inflammatory process was present in all types of repairs. Collagen I deposition
      was higher in the flap repairs. The expression level for the genes related to
      immune response after 6 months from surgery was relatively similar to the control
      group except minor alteration registered in the case of two swine models.
      Conclusion: Our findings indicate a less pronounced proinflammatory response to
      surgical trauma in animal models after flap surgery. The postoperative levels of
      the inflammatory cytokines did not show significant differences after abdominal
      wall reconstruction using flap surgery.

PMID- 29201901
TI  - Development of an Indirect ELISA and Dot-Blot Assay for Serological Detection of
      Rice Tungro Disease.
AB  - Rice tungro disease (RTD) is one of the most destructive diseases of rice in
      South and Southeast Asia. RTD is routinely detected based on visual observation
      of the plant. However, it is not always easy to identify the disease in the field
      as it is often confused with other diseases or physiological disorders. Here we
      report the development of two serological based assays for ease of detection of
      RTD. In this study we had developed and optimized an indirect ELISA and dot-blot
      assay for detection of RTD. The efficiency of both assays was evaluated by
      comparing the specificity and sensitivity of the assays to PCR assay using
      established primer sets. The indirect ELISA showed 97.5% and 96.6%, while the dot
      blot assay showed 97.5% and 86.4% sensitivity and specificity, respectively, when
      compared to established PCR method. The high sensitivity and specificity of the
      two assays merit the use of both assays as alternative methods to diagnose RTD.
      Furthermore, the dot-blot assay is a simple, robust, and rapid diagnostic assay
      that is suitable for field test for it does not require any specialized
      equipment. This is a great advantage for diagnosing RTD in paddy fields,
      especially in the rural areas.

PMID- 29201902
TI  - In Vivo Studies on the Influence of Bacteriophage Preparations on the Autoimmune
      Inflammatory Process.
AB  - Phage preparations used for phage therapy may have not only direct antibacterial
      action but also immunomodulating effects mediated by phages themselves as well as
      by bacterial antigens. Therefore phage application in patients with immune
      disorders, and especially with autoimmune diseases, requires special attention.
      The aim of this study was to investigate the effect of phage lysates
      (staphylococcal phages A3/R, phi200, and MS-1 cocktail, enterococcal phage 15/P,
      Pseudomonas phage 119x, and E. coli T4 phage) as well as purified T4 phage on the
      course of murine collagen-induced arthritis (CIA), commonly used as an animal
      model of rheumatoid arthritis. Intraperitoneal application of phage lysates or
      purified T4 phage did not aggravate the course of autoimmune joint disease.
      Moreover, although endotoxins are known to potentiate CIA, the systemic
      administration of phage lysate of Pseudomonas aeruginosa, which contains debris
      of this Gram-negative bacillus, did not significantly influence CIA although the
      sonicate of the corresponding bacterial strain did. Interestingly, a purified T4
      phage revealed some anti-inflammatory activity when applied under the therapeutic
      scheme. Our preliminary results do not suggest that phages may aggravate the
      symptoms of rheumatoid arthritis. In contrast T4 phage may even exert an
      immunosuppressive effect.

PMID- 29201903
TI  - Cryoablation of Primary Breast Cancer in Patients with Metastatic Disease:
      Considerations Arising from a Single-Centre Data Analysis.
AB  - Background: Patients presenting with stage IV breast cancer might benefit by
      removal of the primary tumor. We report our experience with CT-guided
      cryoablation of the primary tumor, with the aim of evaluating its role in this
      subgroup of patients. Patients and Methods: Data of 35 patients with mean age of
      58 years with breast cancer at stage IV submitted to CT-guided cryoablation of
      the primary tumor between 2010 and 2016 were prospectively evaluated. All
      patients, except three, were preoperatively and postoperatively evaluated with
      breast MRI to assess the extent of tumor necrosis. Retreatment was performed in
      case of incomplete ablation. Results: Mean tumor size was 3.02 +/- 1.4 cm. Six
      patients had multicentric disease. Complete tumor necrosis was 85.7% and 100% at
      2-month and 6-month follow-up, respectively, as 5 patients with tumors > 3 cm
      required a redo cryoablation. No patient developed major complications. Minor
      side effects occurred in 30 patients (82%). All patients were discharged the same
      day of the procedure. During a mean follow-up of 46 months (range 3-84), 7
      patients (20%) experienced local recurrences that were treated with redo
      cryoablation, and 7 (20%) died for disease progression. Conclusions: Our results
      suggest that cryoablation of the primary tumor is safe and effective in the
      treatment of patients presenting with stage IV breast cancer.

PMID- 29201905
TI  - Evaluation of Resins for Stereolithographic 3D-Printed Surgical Guides: The
      Response of L929 Cells and Human Gingival Fibroblasts.
AB  - Additive manufacturing is becoming increasingly important in dentistry for the
      production of surgical guides. The development of cost-effective desktop
      stereolithography (SLA) printing systems and the corresponding resins makes this
      novel technique accessible to dental offices and dental laboratories. The aim of
      the study was to reveal the response of soft tissue cells to Clear and Dental SG
      resins used in desktop SLA printing systems at different stages of processing.
      Cell activity of L929 cells and gingival fibroblasts (GF) in response to the
      materials was examined in indirect and direct monolayer culture models and a
      direct spheroid culture model based on MTT, resazurin-based toxicity assays, and
      live-dead staining. Overall we found that the impact of Clear and Dental SG
      resins on L929 and GF depends on the processing stage of the materials. Liquid
      Clear resin induced a stronger reduction of cell activity compared to Dental SG
      resin. Printing and postcuring reduced the impact on cell activity and viability.
      As in-house 3D printing for surgical guides is getting integrated in the digital
      workflow, our data suggest that careful adherence to processing guidelines
      especially postcuring-is of clinical relevance.

PMID- 29201904
TI  - Correlation in the Coronal Angle between Knee and Hindfoot Was Observed in
      Patients with Rheumatoid Arthritis Unless Talocrural Joint Was Destroyed.
AB  - The purpose of this study is to investigate the compensatory correlation between
      knee and hindfoot in patients with rheumatoid arthritis (RA). This cross
      sectional study included 218 patients (407 lower extremities). Radiographs of the
      hindfoot and full-length posteroanterior hip-to-calcaneus standing radiographs
      were evaluated. The destruction of the hindfoot was evaluated using the Larsen
      grading system. The coronal angular deformity of the knee and hindfoot was
      evaluated by the femorotibial angle (FTA) and the angle between the tibial shaft
      and the entire hindfoot (tibiohindfoot angle, THFA). The correlation between FTA
      and THFA was determined by Pearson's coefficient. For all patients, FTA
      correlated to THFA (R = 0.28, p < 0.001). The correlation was observed as long as
      the talocrural joint was preserved (Larsen grade <= 2), even if the subtalar
      joint had been destroyed (Larsen grade >= 3). However, the correlation was not
      observed when the talocrural joint was destroyed (Larsen grade >= 3, R = -0.02, p
      = 0.94). The pain in the hindfoot did not correlate with FTA or THFA. In
      conclusion, a compensatory deformity of the hindfoot against the deformity of the
      knee was observed in RA, and the correlation was lost when talocrural joint was
      destroyed.

PMID- 29201906
TI  - Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age
      Adjusted D-Dimer Rule Out PE?
AB  - Risk assessment for pulmonary embolism (PE) currently relies on physician
      judgment, clinical decision rules (CDR), and D-dimer testing. There is still
      controversy regarding the role of D-dimer testing in low or intermediate risk
      patients. The objective of the study was to define the role of clinical decision
      rules and D-dimer testing in patients suspected of having a PE. Records of 894
      patients referred for computed tomography pulmonary angiography (CTPA) at a
      University medical center were analyzed. The clinical decision rules overall had
      an ROC of approximately 0.70, while signs of DVT had the highest ROC (0.80). A
      low probability CDR coupled with a negative age-adjusted D-dimer largely excluded
      PE. The negative predictive value (NPV) of an intermediate CDR was 86-89%, while
      the addition of a negative D-dimer resulted in NPVs of 94%. Thus, in patients
      suspected of having a PE, a low or intermediate CDR does not exclude PE; however,
      in patients with an intermediate CDR, a normal age-adjusted D-dimer increases the
      NPV.

PMID- 29201907
TI  - Developmental Testicular Expression, Cloning, and Characterization of Rat HDAC6
      In Silico.
AB  - We had previously reported presence of histone deacetylase 6 (HDAC6) in sperm and
      demonstrated its tubulin deacetylase activity and role in sperm motility in rat.
      In the present study we report its abundant expression in testis, epididymis,
      accessory sex organs, brain, and adrenal. In the testis, HDAC6 transcript and
      protein were observed throughout development. We therefore cloned the gene from
      rat testis using primers for hdac6 (accession number XM_228753.8) in order to
      determine the role of acetylation/deacetylation in spermatogenesis. The cloned
      rat hdac6 gene is ~3.5 kb with 28 exons and 1152 amino acids. We noted 4 single
      nucleotide polymorphisms (SNPs) on exons 2 (G/A), 5 (A/G), 7 (T/C), and 26 (G/T),
      respectively, in this sequence when compared to XM_228753.8. These were further
      validated at both cDNA and gene level. These SNPs resulted in 2 amino acids
      changes, namely, glycine -> arginine and valine -> phenylalanine at protein
      level. Cloned hdac6 overexpressed in HEK293T cells demonstrated significant
      overexpression by IIF. Alpha-tubulin acetylation analysis of the overexpressed
      cell lysate demonstrated that the protein was bioactive. This is the first study
      showing the ontogenic expression in the testis and reporting experimentally
      validated sequence of rat HDAC6 and its structural and functional annotation in
      silico. This sequence has been submitted to GenBank (Accession number Rattus
      KY009929.1).

PMID- 29201908
TI  - Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility:
      An Experimental Study.
AB  - Objectives: We aimed to investigate the effect of a carbohydrate-rich diet on
      detrusor contractility in rats. Materials and Methods: Sprague-Dawley rats were
      randomized into two groups. The control group received regular food and water.
      The study group received carbohydrate-rich diet for six weeks. The rats' detrusor
      muscle was isolated for pharmacological and histopathological examinations.
      Results: In the control and study groups, mean body weights were 431.5 +/- 27.6 g
      and 528.0 +/- 36.2 g, respectively (p < 0.001). Electrical stimulation of the
      detrusor strips of the control group resulted in gradual contraction. A decreased
      contractile response was shown in the study group. Acetylcholine in 10-7-10-3
      molar concentration produced a decreased contractile response in the study group,
      compared to the control group (p < 0.01). The study group showed marked
      subepithelial and intermuscular fibrosis in the bladder. Conclusion: Carbohydrate
      rich diet causes marked subepithelial and extracellular fibrosis and changes in
      contractility in the detrusor within a six-week period. Changes have higher costs
      in therapeutic choices and correction of these changes remains difficult. Putting
      an end to carbohydrate-rich diet would seem to be more cost-effective than
      dealing with the effects of consuming it in high proportions which should be the
      national policy worldwide.

PMID- 29201909
TI  - Quantitative Serum Proteomic Analysis of Essential Hypertension Using iTRAQ
      Technique.
AB  - Essential hypertension (EH) is a risk factor for some severe diseases. This study
      aimed to screen out serum special proteins and seek interaction between them,
      which would provide new therapeutic targets and elucidate the comprehensive
      pathophysiological mechanism for EH. Patients with EH (Group A, n = 47) and
      healthy controls (HC) (Group B, n = 47) were recruited in this study. Serums from
      the two groups were analyzed with isobaric tags for relative and absolute
      quantitation coupled two-dimensional liquid chromatography followed by
      electrospray ionization-tandem mass spectrometry technique, while the candidate
      special proteins were verified with ELISA and western blot. A total of 404
      proteins were identified, of which 30 proteins were upregulated (>1.2-fold, p <
      0.05) and 81 proteins were downregulated (<0.833-fold, p < 0.05) compared with HC
      group. With GO, KEGG analysis, and literature retrieval, 4 proteins, cathepsin G,
      transforming growth factor beta-1, hyaluronidase-1, and kininogen-1, were found
      jointly involved in the renin-angiotensin-aldosterone system and kallikrein-kinin
      system. The profiles of these 4 candidate proteins were confirmed with ELISA and
      western blot. The concentration variation of these 4 proteins could better
      predict the occurrence and illustrate the pathophysiological mechanism of EH. And
      their discovery may help pave the way for exploring new therapies of EH.

PMID- 29201910
TI  - Body Schema Illusions: A Study of the Link between the Rubber Hand and
      Kinesthetic Mirror Illusions through Individual Differences.
AB  - Background: The well-known rubber hand paradigm induces an illusion by having
      participants feel the touch applied to a fake hand. In parallel, the kinesthetic
      mirror illusion elicits illusions of movement by moving the reflection of a
      participant's arm. Experimental manipulation of sensory inputs leads to emergence
      of these multisensory illusions. There are strong conceptual similarities between
      these two illusions, suggesting that they rely on the same neurophysiological
      mechanisms, but this relationship has never been investigated. Studies indicate
      that participants differ in their sensitivity to these illusions, which provides
      a possibility for studying the relationship between these two illusions. Method:
      We tested 36 healthy participants to confirm that there exist reliable individual
      differences in sensitivity to the two illusions and that participants sensitive
      to one illusion are also sensitive to the other. Results: The results revealed
      that illusion sensitivity was very stable across trials and that individual
      differences in sensitivity to the kinesthetic mirror illusion were highly related
      to individual differences in sensitivity to the rubber hand illusion.
      Conclusions: Overall, these results support the idea that these two illusions may
      be both linked to a transitory modification of body schema, wherein the most
      sensitive people have the most malleable body schema.

PMID- 29201912
TI  - Relationship between Activities of Daily Living and Readmission within 90 Days in
      Hospitalized Elderly Patients with Heart Failure.
AB  - Aims: To examine the relationship between activities of daily living (ADL) and
      readmission within 90 days and assess the cutoff value of ADL to predict
      readmission in hospitalized elderly patients with heart failure (HF). Methods:
      This cohort study comprised 589 consecutive patients with HF aged >=65 years, who
      underwent cardiac rehabilitation from May 2012 to May 2016 and were discharged
      home. We investigated patients' characteristics, basic attributes, and ADL (motor
      and cognitive Functional Independence Measure [FIM]). We analyzed the data using
      the unpaired t-test, chi2 test, Cox proportional hazard model, receiver operating
      characteristic (ROC) curve, and Kaplan-Meier method. Results: Of 589 patients,
      113 met the criteria, and they were divided into the nonreadmission (n = 90) and
      readmission groups (n = 23). Age, body mass index, New York Heart Association
      class, hemoglobin level, and motor FIM score were significantly different between
      the two groups (p < 0.05). The body mass index (hazard ratio [HR]: 0.87; p <
      0.05) and motor FIM score (HR: 0.94; p < 0.01) remained statistically
      significant. The cutoff value for the motor FIM score determined by ROC curve
      analysis was 74.5 points (area under the curve = 0.78; p < 0.001). Conclusion:
      The motor FIM score in elderly patients with HF was an independent predictor of
      rehospitalization within 90 days.

PMID- 29201911
TI  - Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production
      of Interferon-beta through Its Deubiquitinase Activity.
AB  - Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute
      respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine
      epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus
      (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-)
      induced interferon (IFN-beta) production. Recently, the crystal structure of
      transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar
      to that of SARS-CoV PL2pro, which may antagonize host innate immunity. However,
      very little is known about whether TGEV PL1 can antagonize host innate immune
      response. Here, we presented evidence that TGEV PL1 encoded by the replicase gene
      could suppress the IFN-beta expression and inhibit the nuclear translocation of
      interferon regulatory factor 3 (IRF3). The ability to antagonize IFN-beta
      production was dependent on the intact catalytic activity of PL1. Furthermore,
      TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the
      retinoic acid-induced gene I- (RIG-1-) and stimulator of interferon gene- (STING
      ) dependent IFN expression. Our data collectively suggest that TGEV PL1 can
      inhibit the IFN-beta expression and interfere with RIG-1- and STING-mediated
      signaling through a viral DUB activity. Our study has yielded strong evidence for
      the TGEV PL1 mechanisms that counteract the host innate immunity.

PMID- 29201913
TI  - Proanthocyanidins Attenuation of H2O2-Induced Oxidative Damage in Tendon-Derived
      Stem Cells via Upregulating Nrf-2 Signaling Pathway.
AB  - Proanthocyanidins (PCs) have shown inhibition of oxidative damage by improving
      Nrf-2 expression in many tissues. However, the cytoprotective effects of PCs on
      H2O2-induced tendon damage have not been verified. The current study was aimed at
      assessing the cytoprotection of PCs on the oxidative cellular toxicity of tendon
      derived stem cells (TDSCs) induced by H2O2. The TDSCs were isolated from patellar
      tendons of Sprague Dawley (SD) rats, and the cells after third passage were used
      for subsequent experiments. The isolated cells were identified by flow cytometry
      assay and multidifferentiation potential assay. Cell Counting Kit-8 assay was
      performed to examine cell viability. Real-Time PCR and Western Blot were employed
      to, respectively, assess the mRNA and protein expressions of Nrf-2, GCLM, NQO-1,
      and HO-1. PCs significantly improved the cell viability of TDSCs. Furthermore,
      H2O2 upregulated Nrf-2, GCLM, NQO-1, and HO-1 without significant difference,
      while the proteins expressions were increased with significant difference in PCs
      group and PCs + H2O2 cotreated group. All the findings indicated that PCs could
      protect against the oxidative damage induced by H2O2 in TDSCs, and the
      cytoprotective effects might be due to the ability of PCs to activate the
      expressions of GCLM, HO-1, and NQO-1 via upregulating Nrf-2 signaling pathway.

PMID- 29201915
TI  - Exploring the Concept of Degrees of Maternal Morbidity as a Tool for Surveillance
      of Maternal Health in Latin American and Caribbean Settings.
AB  - Objectives: To assess a birth registry to explore maternal mortality and
      morbidity and their association with other factors. Study Design: Exploratory
      multicentre cross-sectional analysis with over 700 thousand childbirths from
      twelve Latin American and Caribbean countries between 2009 and 2012. The WHO
      criteria for maternal morbidity were employed to split women, following a
      gradient of severity of conditions, into (1) maternal death (MD); (2) maternal
      near miss (MNM); (3) potentially life-threatening conditions (PLTC); (4) less
      severe maternal morbidity (LSMM); (5) any maternal morbidity; and (6) women with
      no maternal morbidity. Their prevalence and estimated risks of adverse maternal
      outcomes were assessed. Results: 712,081 childbirths had a prevalence of MD and
      MNM of 0.14% and 3.1%, respectively, while 38% of women had experienced
      morbidity. Previous maternal morbidity was associated with higher risk of adverse
      maternal outcomes and also the extremes of reproductive ages, nonwhite ethnicity,
      no stable partner, no prenatal care, smoking, drug and alcohol use, elective C
      section, or induction of labour. Poorer perinatal outcomes were proportional to
      the severity of maternal outcomes. Conclusions: The findings corroborate WHO
      concept regarding continuum of maternal morbidity, reinforcing its importance in
      preventing adverse maternal outcomes and improving maternal healthcare in
      different settings.

PMID- 29201914
TI  - Acute Right Ventricular Dysfunction in Intensive Care Unit.
AB  - The role of the left ventricle in ICU patients with circulatory shock has long
      been considered. However, acute right ventricle (RV) dysfunction causes and
      aggravates many common critical diseases (acute respiratory distress syndrome,
      pulmonary embolism, acute myocardial infarction, and postoperative cardiac
      surgery). Several supportive therapies, including mechanical ventilation and
      fluid management, can make RV dysfunction worse, potentially exacerbating shock.
      We briefly review the epidemiology, pathophysiology, diagnosis, and
      recommendations to guide management of acute RV dysfunction in ICU patients. Our
      aim is to clarify the complex effects of mechanical ventilation, fluid therapy,
      vasoactive drug infusions, and other therapies to resuscitate the critical
      patient optimally.

PMID- 29201917
TI  - The Prognostic Value of Combined Smoking and Alcohol Consumption Habits for the
      Estimation of Cause-Specific Mortality in Middle-Age and Elderly Population:
      Results from a Long-Term Cohort Study in Lithuania.
AB  - Aim: To evaluate the prognostic value of combined smoking and alcohol consumption
      habits for the estimation of cause-specific mortality risk in middle-age and
      elderly population. Methods: The study presents data from the four surveys. A
      random sample of 6,729 subjects aged 35-64 years was selected for statistical
      analysis. During the follow-up of 31 years (1983-2014), there were 2,158 deaths
      from any cause. Multivariate Cox's proportional hazards models were used to
      estimate hazard ratios (HR) for all-cause mortality and Competing Risk Regression
      analysis was used to estimate subdistribution hazard risk (SHR) for cause
      specific mortality. Results: Smoking clearly increased the risk of all-cause
      mortality and mortality from cancer and cardiovascular disease (CVD), but alcohol
      use had little effect in men aged 35-64 years. However, heavy alcohol consumption
      (>14 units/week) increased the risk of all-cause mortality and mortality from
      external causes in the never-smokers men group who drank alcohol of 1-14
      units/week (HR 2 = 1.57 and SHR 2 = 2.40, resp.). Conclusions: The smoking habits
      and alcohol consumption are modifiable risk factors, and thus efforts to support
      abstinence from alcohol and smoking use should be a public health priority.

PMID- 29201916
TI  - Biochemical and Genetical Responses of Phoenix dactylifera L. to Cadmium Stress.
AB  - The cadmium (Cd), a heavy metal, causes toxicity, which leads to hampering the
      growth and development of the plant. The molecular and biochemical approaches
      were used for the investigation of antioxidant system response and genotoxicity
      in date palm (Phoenix dactylifera L.) cv. Sagai in pot experiment having Cd. The
      root length was more affected than the shoot length as more accumulation of Cd
      occurs in roots. Fresh weights of root and shoot were reduced significantly in
      treated plants as compared to the control. The proline content was increased at
      low concentration of Cd (300 uM-CdCl2) than the medium and high concentrations
      (600 and 900 uM-CdCl2), respectively. The thiobarbituric acid reactive substances
      (TBARS) content was increased at 600 and 900 uM-CdCl2 compared to the plants
      treated at 300 uM-CdCl2 and controls. Antioxidant enzymatic assay was performed
      under Cd stress and compared with control plants. The catalase (CAT) and
      superoxide dismutase (SOD) activities were found to be high in plants treated
      with CdCl2 at 300 uM compared to at 600 and 900 uM-CdCl2, respectively. The
      genotoxicity of Cd was assessed using the inter-simple sequence repeat (ISSR)
      marker where all treated and control plants were clustered into three main groups
      based on genetic similarity. P. dactylifera plants were found to be more
      divergent at high Cd stress as compared to control and plants treated at low
      concentration of Cd.

PMID- 29201919
TI  - Dynamics of Insulin Secretion from EndoC-betaH1 beta-Cell Pseudoislets in
      Response to Glucose and Other Nutrient and Nonnutrient Secretagogues.
AB  - The dynamics of insulin secretion were characterized in response to a variety of
      physiological and pharmacological stimulators and other compounds in perifused
      pseudoislets generated from cells of the EndoC-betaH1 beta-cell line. Perifusion
      of EndoC-betaH1 pseudoislets with the physiological stimulus glucose (16.7 mM)
      induced sustained insulin secretion, which was inhibited by mannoheptulose. The
      adenylate cyclase activators IBMX and forskolin strongly potentiated this
      secretion. Glibenclamide, a Kir 6.2 potassium channel blocker, and Bay K 8644, an
      opener of the voltage-sensitive Ca2+ channel, also potentiated glucose-induced
      insulin secretion. The dynamics of insulin secretion from EndoC-betaH1
      pseudoislets were characterized by an insulin secretory response to glucose
      starting within 1-2 min and passing over without interruption into a sustained
      phase of insulin release for the whole stimulation period. This lack of a
      transient decline between the first and the second phases of insulin release is
      an indication for a quick supply of insulin secretory granules from the reserve
      pool to the docking sites below the plasma membrane. Thereby, new secretory
      granules are directly made available for sustained exocytosis of insulin in EndoC
      betaH1 beta-cells. The study shows that EndoC-betaH1 beta-cell pseudoislets are
      well suited for kinetic analyses of insulin secretion.

PMID- 29201920
TI  - Diabetic Nephropathy: From Pathophysiology to Treatment.

PMID- 29201918
TI  - The Role of Insulin Receptor Isoforms in Diabetes and Its Metabolic and Vascular
      Complications.
AB  - The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and
      IRB. The differential physiological and pathological role of both isoforms is not
      completely known, and it is determinant the different binding affinity for
      insulin-like growth factor. IRB is more abundant in adult tissues and it exerts
      mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal
      and prenatal period and exerts mitogenic actions. However, the change in the
      expression profile of both IR isoforms and its dysregulation are associated with
      the development of different pathologies, such as cancer, insulin resistance,
      diabetes, obesity, and atherosclerosis. In some of them, there is a significant
      increase of IRA/IRB ratio conferring a proliferative and migratory advantage to
      different cell types and favouring IGF-II actions with a sustained detriment in
      the metabolic effects of insulin. This review discussed specifically the role of
      IR isoforms as well as IGF-IR in diabetes and its associated complications as
      obesity and atherosclerosis. Future research with new IR modulators might be
      considered as possible targets to improve the treatment of diabetes and its
      associated complications.

PMID- 29201921
TI  - Selective Screening Strategies for Gestational Diabetes: A Prospective Cohort
      Observational Study.
AB  - Aim: We aimed to develop a prediction model for the diagnosis of gestational
      diabetes and to evaluate the performance of published prediction tools on our
      population. Methods: We conducted a cohort study on nondiabetic women < 26 weeks
      gestation at a level 1 clinic in Johannesburg, South Africa. At recruitment,
      participants completed a questionnaire and random basal glucose and HbA1c were
      evaluated. A 75 g 2-hour OGTT was scheduled between 24-28 weeks gestation, as per
      FIGO guidelines. A score was derived using multivariate logistic regression.
      Published scoring systems were tested by deriving ROC curves. Results: In 554
      women, RBG, BMI, and previous baby >= 4000 g were significant risk factors
      included for GDM, which were used to derive a nomogram-based score. The logistic
      regression model for prediction of GDM had R2 0.143, Somer's Dxy rank correlation
      0.407, and Harrell's c-score 0.703. HbA1c did not improve predictive value of the
      nomogram at any threshold (e.g,. at probability > 10%, 25.6% of cases were
      detected without the HbA1c, and 25.8% of cases would have been detected with the
      HbA1c). The 9 published scoring systems performed poorly. Conclusion: We propose
      a nomogram-based score that can be used at first antenatal visit to identify
      women at high risk of GDM.

PMID- 29201922
TI  - Immunization with Bivalent Flagellin Protects Mice against Fatal Pseudomonas
      aeruginosa Pneumonia.
AB  - Pseudomonas aeruginosa lung infections present a major challenge to healthcare
      systems worldwide because they are commonly associated with high morbidity and
      mortality. Here, we demonstrate the protective efficacy of type a and b
      flagellins (bivalent flagellin) against acute fatal pneumonia in mice. Mice
      immunized intranasally with a bivalent flagellin vaccine were challenged by
      different flagellated strains of P. aeruginosa in an acute pneumonia model.
      Besides the protective effect of the vaccine, we further measured the host innate
      and cellular immunity responses. The immunized mice in our study were protected
      against both strains. Remarkably, active immunization with type a or b flagellin
      significantly improved survival of mice against heterologous strain compared to
      flagellin a or b antisera. We also showed that after an intranasal challenge by
      P. aeruginosa strain, neutrophils are recruited to the airways of vaccinated
      mice, and that the bivalent flagellin vaccine was proved to be protective by the
      generated CD4+IL-17+ Th17 cells. In conclusion, bivalent flagellin vaccine can
      confer protection against different strains of P. aeruginosa in an acute
      pneumonia mouse model by eliciting effective cellular and humoral immune
      responses, including increased IL-17 production and improved opsonophagocytic
      killing.

PMID- 29201923
TI  - Regulation of Leukocyte Recruitment to the Spleen and Peritoneal Cavity during
      Pristane-Induced Inflammation.
AB  - Chronic inflammation is associated with an increased number of leukocytes in the
      spleen, which are then redirected to the site of inflammation. However, it
      remains unknown how leukocyte recruitment is regulated. Herein, chronic
      inflammation was induced by intraperitoneal injection of pristane into mice.
      Leukocytes in the spleen or in the peritoneal cavity were quantified by flow
      cytometry. We found that the loss of IL-6 decreased macrophage recruitment to the
      spleen and the peritoneal cavity during pristane-induced inflammation. The loss
      of TNFalpha delayed the recruitment of neutrophils and macrophages to the spleen
      and inhibited the recruitment of neutrophils, macrophages, B cells, and T cells.
      The recruitment of neutrophils and macrophages into the spleen or peritoneal
      cavity was largely inhibited in the absence of LTalpha. The loss of TNFalpha
      receptor 1/2 resulted in reduced recruitment of neutrophils, macrophages, and
      dendritic cells into the spleen, but only neutrophil recruitment was inhibited in
      the peritoneal cavity. Similarly, a lack of B cells significantly impeded the
      recruitment of neutrophils, macrophages, and dendritic cells to the spleen.
      However, only macrophage recruitment was inhibited in the absence of T cells in
      the spleen. These data provide insight into the development of chronic
      inflammation induced by noninfectious substances.

PMID- 29201924
TI  - Flexion Gap in the Isolated Posterior Cruciate Ligament-Injured Knee Affects
      Symptom Relief After Conservative Treatment: A Case-Control Study.
AB  - Background: The posterior cruciate ligament (PCL) is a primary stabilizer of the
      knee in the posterior direction. However, PCL deficiency presents a clinical
      paradox because the outcome of PCL deficiency ranges from total disability to
      uninterrupted participation in competitive athletics. Purpose: To investigate
      whether posterior laxity (PL) and the flexion gap (FG) influence the results of
      the conservative treatment of isolated PCL injuries. Study Design: Case-control
      study; Level of evidence, 3. Methods: A total of 27 patients (23 men, 4 women;
      mean age, 33 +/- 14 years) with isolated PCL injuries between 2007 and 2013 were
      included in this study. All patients had been treated conservatively for more
      than 6 months. Nineteen patients achieved excellent relief of their symptoms
      (conservative treatment [C] group). Eight patients underwent PCL reconstruction
      owing to their symptoms (surgical treatment [S] group). Side-to-side differences
      of the FG and the PL were retrospectively measured on axial radiographs and on
      lateral radiographs with gravity sag views, respectively, and the degree of PCL
      injury was graded as I (PL, <5 mm) in 7 patients and II (PL, 5 to <10 mm) in 20
      patients. Results: The mean PL and FG were 6.9 +/- 2.5 mm and 2.0 +/- 1.8 mm,
      respectively. A mild positive correlation between the PL and the FG was observed
      (r = 0.47, P = .02). The mean PL and FG were 6.5 +/- 2.9 mm and 1.2 +/- 1.0 mm in
      the C group and 7.7 +/- 1.3 mm and 3.8 +/- 2.0 mm in the S group, respectively.
      The FG in the C group was significantly smaller than that in the S group (P <
      .05), although there was no significant difference between the groups for PL. All
      patients with grade I injury belonged to the C group, for which the FG was less
      than 2 mm in all cases. Eight of the patients with grade II injury were in the S
      group, and their FG was more than 2 mm, except in 1 patient. The FG performed
      better with an area under the receiver operating characteristic curve of 0.924
      (95% CI, 0.000-1.000) compared with 0.599 (95% CI, 0.388-0.809) for the PL.
      Discrimination between the C and S groups with a cutoff set at 2.30 mm for the FG
      and 7.45 mm for the PL showed a sensitivity of 75.0% and 75.0% and a specificity
      of 89.5% and 52.6%, respectively. Conclusion: Considering that the FG affects the
      outcome of conservative treatment, it could be a factor in the indication for the
      surgical treatment of isolated PCL injuries.

PMID- 29201925
TI  - A Comparison of Nonoperative and Operative Treatment of Complete Proximal
      Hamstring Ruptures.
AB  - Background: The early repair of acute proximal hamstring ruptures provides better
      clinical results than delayed repair. However, it is unclear how nonoperative
      treatment compares with the operative treatment of these injuries. Purpose: To
      compare the clinical results of the nonoperative and operative treatment of acute
      proximal hamstring ruptures. Study Design: Cohort study; Level of evidence, 3.
      Methods: A total of 25 patients with complete, retracted proximal hamstring
      ruptures presenting to 1 institution were retrospectively reviewed. All patients
      were given the option of proximal hamstring repair at the time of the initial
      evaluation. Patients with at least 12 months of follow-up from the time of
      surgery or injury were included in the evaluation. Both nonoperative and
      operative treatment groups were evaluated using the same outcome measures. The
      primary outcome measure was the Lower Extremity Functional Scale (LEFS).
      Secondary outcome measures included the Short Form-12 (SF-12) physical and mental
      component summaries, strength testing, a single-leg hop test, the patient's
      perception of strength, and the ability to return to activity. Results: There
      were 11 patients treated nonoperatively, with a mean follow-up of 2.48 +/- 3.66
      years, and 14 patients treated operatively, with a mean follow-up of 3.56 +/-
      2.11 years. The mean LEFS scores for the nonoperative and operative groups were
      68.50 +/- 7.92 and 74.71 +/- 5.38, respectively (P = .07). No statistical
      differences were found between the groups regarding SF-12 scores and mean single
      leg hop distance compared with the uninjured leg. Isometric testing of the
      injured hamstring in the nonoperative group demonstrated significant clinical
      weakness compared with the uninjured side at both 45 degrees  and 90 degrees  of
      flexion (57.54% +/- 7.8% and 67.73% +/- 18.8%, respectively). Isokinetic testing
      of the injured leg in the operative group demonstrated 90.87% +/- 16.3% strength
      of the uninjured leg. All patients in the operative group were able to return to
      preinjury activities, whereas 3 patients in the nonoperative group were unable to
      return (chi-square = 4.33, P = .07). Conclusion: Patients with acute proximal
      hamstring ruptures treated surgically regained approximately 90% strength of the
      uninjured extremity and tended to have a greater likelihood of returning to
      preinjury activities than patients treated nonoperatively.

PMID- 29201926
TI  - Factors Associated With Physician Loss in Anterior Cruciate Ligament
      Reconstruction Malpractice Lawsuits.
AB  - Background: Anterior cruciate ligament (ACL) reconstruction is among the most
      common orthopaedic procedures, with its incidence doubling over the past decade.
      To date, no studies have analyzed litigation after ACL reconstruction. Purpose:
      To characterize the causes of malpractice litigation after ACL reconstruction.
      Study Design: Cross-sectional study. Methods: A retrospective review of
      malpractice lawsuits after ACL reconstruction was performed using VerdictSearch,
      a large legal claims database encompassing nearly 180,000 legal cases, from
      February 1988 to May 2015. Settlement rates and physician loss rates were
      calculated along with 95% CIs for each complication type, and analysis of
      variance was used to compare all indemnity payments. Results: Of a total 30
      lawsuits, 5 (16.7%) settled out of court. The 3 most common complications leading
      to litigation were prolonged pain (n = 5, 16.7%), infection (n = 5, 16.7%), and
      malpositioned graft (n = 5, 16.7%). Of the 25 cases that went to court, 8 (32.0%)
      ended in favor of the plaintiff (physician loss). Damage to a neurovascular
      structure resulted in the highest indemnity payment (mean, $2,012,926 +/-
      $1,076,530; P = .021). Lawsuits for which pain or loss of range of motion was the
      only complication were significantly more likely to end in a physician victory (P
      = .04) and lower indemnity payments ($87,500 vs $678,715, respectively). Cases
      that involved a surgical technical error were more likely to result in a
      physician loss (P = .01), with malpositioned grafts having a significantly higher
      loss rate than average (75% vs 32%, respectively). Conclusion: After ACL
      reconstruction, physicians are more likely to win malpractice suits if pain or
      limited range of motion is the only complaint and less likely to win if a
      surgical error was alleged. These findings may help to set patient expectations
      and provide adequate guidance during the informed consent process.

PMID- 29201927
TI  - Radiographic Location Does Not Ensure a Precise Anatomic Location of the Femoral
      Fixation Site in Medial Patellofemoral Ligament Reconstruction.
AB  - Background: A frequently used method to determine the anatomic femoral fixation
      point in the operating room during medial patellofemoral ligament (MPFL)
      reconstruction is the radiographic method. However, the ability of this
      radiological method to establish an anatomic femoral attachment point might not
      be as accurate as expected. Purpose: (1) To evaluate the accuracy of the
      radiological method to locate the anatomic femoral fixation point in MPFL
      reconstruction surgery and (2) to determine the factors influencing the
      predictability of this method to obtain this objective. Study Design: Cohort
      study (diagnosis); Level of evidence, 2. Methods: A total of 100 consecutive 3
      dimensional computed tomography (3D CT) knee examinations were performed at 0
      degrees  of extension in 87 patients treated for chronic lateral patellar
      instability. For each knee, 2 virtual 7 mm-diameter femoral tunnels were created:
      1 using the adductor tubercle as a landmark (anatomic tunnel) and the other
      according to the radiological method described by Schottle et al (radiographic
      tunnel). We measured the percentage of overlap between both tunnels. Moreover, of
      the 100 included knees, 10 were randomly selected for a variability study.
      Results: Considering an overlap area greater than 50% as reasonable, the
      radiographic method achieved this in only 38 of the 100 knees. Intrarater and
      interrater reliability were excellent. There was a trend for female patients with
      severe trochlear dysplasia to have less overlap. This model accounted for 64.2%
      of the initial variability in the data. Conclusion: An exact anatomic femoral
      tunnel placement could not be achieved with the radiographic method. Radiography
      provided only an approximation and should not be the sole basis for the femoral
      attachment location. Moreover, in female patients with severe trochlear
      dysplasia, the radiographic method was less accurate in determining the anatomic
      femoral fixation point, although differences were not statistically significant.

PMID- 29201928
TI  - Abnormal Pain Response After a Compensable Shoulder Injury.
AB  - Background: The role of psychosocial factors has been established in patients
      with shoulder abnormalities. However, the prevalence of exaggerated pain
      behaviors and their association with the characteristics of injured workers have
      not been well studied. Purpose: To examine the prevalence of abnormal pain
      responses (APRs) in workers with active workers' compensation claims for a
      shoulder injury and to examine the differences between workers with APRs versus
      workers without APRs. Study Design: Cross-sectional study; Level of evidence, 3.
      Methods: An analysis of electronic data files of injured workers was completed.
      An APR was defined as an exaggerated pain response during a clinical examination,
      including facial grimacing, shaking, withdrawal, nonanatomic dermatome or myotome
      disturbances, increased tenderness, regional symptoms, and verbal utterances such
      as groaning, moaning, or gasping. To control for potential confounders, patients
      with positive APRs (APR group) were matched with injured workers without APRs
      (control group) seen in the same clinic and matched for sex, age, and surgical
      candidacy. Results: Data from 1000 workers who had sustained a shoulder injury at
      work and who were referred for an early assessment by an orthopaedic surgeon and
      a physical therapist were reviewed. A total of 86 (9%) injured workers (mean age,
      47 +/- 11 years; 55 [64%] female) demonstrated APRs and were matched with 86
      injured workers without APRs. There were no statistically significant between
      group differences in the wait time, mechanism of injury, coexisting comorbidity,
      type of abnormality, or medication consumption. The APR group reported higher
      levels of disability (P < .0001) and psychological problems (P < .0001),
      presented with more inconsistency in range of motion (P = .04), and had more
      limitations at work (P = .02). Conclusion: The presence of an APR after a
      compensable shoulder injury was associated with higher reports of disability and
      psychological problems. Patients with positive APRs were more likely to be off
      work and less likely to perform full duties.

PMID- 29201929
TI  - Evaluation of the Schottle Technique in the Pediatric Knee.
AB  - Background: The Schottle point is commonly used for anatomic femoral tunnel
      placement during medial patellofemoral ligament (MPFL) reconstruction. This
      technique has not been previously validated in the skeletally immature patient,
      in whom femoral tunnel placement may put the distal femoral physis at risk of
      iatrogenic injury. Hypothesis: Interobserver reliability for femoral tunnel
      placement will be higher in adult knees compared with pediatric knees. Study
      Design: Cross-sectional study (diagnosis); Level of evidence, 3. Methods: We
      selected 30 perfect lateral radiographs for this study: 20 from pediatric knees
      (mean patient age, 10 years; range, 8-11 years) and 10 from adult knees (mean
      patient age, 18.5 years; range, 18-23 years). Six observers with varying levels
      of clinical experience evaluated each radiograph and approximated the site of the
      MPFL femoral tunnel using the Schottle technique. Intra- and interobserver
      reliabilities for femoral tunnel placement were evaluated. Statistical analysis
      was used to compare measurements. Results: During initial interobserver
      measurements, the diameter of the composite perfect circles averaged 9.0 and 6.8
      mm in adult and pediatric knees, respectively (P = .004). At repeat measurement,
      circles averaged 9.8 and 7.3 mm in adult and pediatric knees, respectively (P =
      .0001). Femoral tunnel placement intraobserver variance averaged 2.9 mm in adult
      knees (range, 1.9-4.0 mm) and 2.3 mm in pediatric knees (range, 1.9-2.9 mm). This
      difference was not significant (P = .14). Conclusion: This study demonstrated
      that interobserver variance is actually greater in adult knees compared with
      pediatric knees, although interobserver variance was significantly different for
      both populations. Additionally, intraobserver variance is small on repeat
      measures, demonstrating that the Schottle technique is reproducible for
      individual observers. Sources of this increased variance between observers are
      differences in agreement on the bony landmarks required for the Schottle
      technique. Due to this variability in tunnel placement, we recommend caution when
      the Schottle technique is used in pediatric knees to avoid iatrogenic injury to
      the distal femoral physis during femoral tunnel placement.

PMID- 29201930
TI  - A Case of Sub-Diaphragmatic Abscess after Injection of Botulinum Toxin to Treat
      Achalasia.
AB  - Achalasia is a disorder of the esophagus characterized by decreased lower
      esophageal sphincter (LES) relaxation and absence of esophageal peristalsis.
      Botulinum toxin (BT) injection targeting the LES has been used in the treatment
      of achalasia and other esophageal motility disorders, and it is considered to be
      safe and effective for short-term symptomatic relief. Serious adverse events of
      this procedure are rare. We report the case of an 83-year-old woman treated with
      BT injection for achalasia who subsequently developed a subdiaphragmatic abscess.

PMID- 29201931
TI  - Colchicine-Induced Hepatotoxicity.
AB  - Drug-induced injury (DILI) is a frequent cause of abnormal liver tests and a
      leading cause of liver failure in the United States. Colchicine has long been
      used as a systemic anti-inflammatory agent for treatment of gout by inhibiting
      mitotic activity and neutrophil function. We present the first case of colchicine
      induced hepatoxicity, supported by histopathologic findings characteristic of
      colchicine-induced injury and resolution of liver enzyme abnormalities after its
      discontinuation. Colchicine-associated DILI has implications for the evaluation
      of patients with abnormal liver tests and gout, especially for patients with
      alcoholism and non-alcoholic fatty liver disease, in whom there is an increased
      incidence of gout.

PMID- 29201932
TI  - Novel Use of an Endoscopic Suturing Device to Repair a Cholecystoduodenal
      Fistula.

PMID- 29201933
TI  - RATA: A method for high-throughput identification of RNA bound transcription
      factors.
AB  - Long non-coding RNAs (lncRNAs) regulate critical cellular processes and their
      dysregulation contributes to multiple diseases. Although only a few lncRNAs have
      defined mechanisms, many of these characterized lncRNAs interact with
      transcription factors to regulate gene expression, suggesting a common mechanism
      of action. Identifying RNA-bound transcription factors is especially challenging
      due to inefficient RNA immunoprecipitation and low abundance of many
      transcription factors. Here we describe a highly sensitive, user-friendly, and
      inexpensive technique called RATA (RNA-associated transcription factor array),
      which utilizes a MS2-aptamer pulldown strategy coupled with transcription factor
      activation arrays for identification of transcription factors associated with a
      nuclear RNA of interest. RATA requires only ~5 million cells and standard
      molecular biology reagents for multiplexed identification of up to 96
      transcription factors in 2-3 d. Thus, RATA offers significant advantages over
      other technologies for analysis of RNA-transcription factor interactions.

PMID- 29201934
TI  - Evidence for rapid localist plasticity in the ventral visual stream: The example
      of words.
AB  - Our recent work has shown that the Visual Word Form Area (VWFA) in left
      occipitotemporal cortex contains an orthographic lexicon based on neuronal
      representations highly selective for individual written real words (RW) and that
      learning novel words selectively increases neural specificity in the VWFA. But,
      how quickly does this change in neural tuning occur and how much training is
      required for new words to be codified in the VWFA? Here we present evidence that
      plasticity in the VWFA from broad to tight tuning can be obtained in a short time
      span, with no explicit training, and with comparatively few exposures, further
      strengthening the case for a highly plastic visual lexicon in the VWFA and for
      localist representations in the visual processing hierarchy.

PMID- 29201935
TI  - A Review of Contemporary Assessment Tools for Use with Transgender and Gender
      Nonconforming Adults.
AB  - There is increasing recognition of the need for culturally sensitive services for
      individuals who identify as transgender or gender non-conforming (TGNC), and only
      recently have empirical studies appeared in the literature that inform best
      practices for TGNC people. Competent, culturally appropriate clinical services
      and research depend upon methodologically sound assessment of key constructs, but
      it is unclear whether appropriate self-report or clinician-rated assessment tools
      for adults exist. This paper reviewed existing published measures to identify
      areas of strength as well as existing gaps in the available research. The search
      strategy for this systematic review identified any published paper describing a
      self-report or clinician-rated scale for assessing transgender-related concerns.
      Each measure was reviewed for information on its scope, reliability, validity,
      strengths, limitations, and source. The majority of these questionnaires were
      developed with the TGNC communities and targeted important factors that affect
      quality of life for TGNC people. Limitations included limited evidence for
      validity, reliability, and sensitivity to change. Overall, the field is moving in
      the direction of TGNC-affirming assessment, and promising measures have been
      created to monitor important aspects of quality of life for TGNC people. Future
      research should continue to validate these measures for use in assessing clinical
      outcomes and the monitoring of treatment progress.

PMID- 29201937
TI  - Variance in Mood Symptoms Across Menstrual Cycles: Implications for Premenstrual
      Dysphoric Disorder.
AB  - Premenstrual dysphoric disorder (PMDD) remains a controversial diagnosis: Some
      authors have argued that it pathologizes normal mood changes, and others have
      questioned the need for daily mood reports across multiple cycles. In the present
      study, we examined changes in mood among psychologically healthy young
      participants with regular menstrual cycles. We collected daily reports of
      negative mood (depression, nervousness, irritability, and fatigue) across two to
      six consecutive cycles from 27 participants aged 18-35 years, and we used
      variance decomposition analyses to examine how much of the variance in these
      daily reports was due to day, cycle, and individual. The majority of variance
      (79%-98%) was due to daily fluctuations and did not conform to a standard pattern
      of premenstrual rise/postmenstrual fall. These findings suggest that PMDD is not
      simply an exaggeration of mood patterns typical for psychologically healthy
      people. Individual patterns were relatively stable from cycle to cycle; thus
      tracking deviations from a patient's own normative mood patterns may have greater
      clinical utility than deviation from a presumptive norm.

PMID- 29201936
TI  - Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin
      Pathway.
AB  - There is great potential for engineering cellular therapeutics by repurposing
      biological systems. Here, we report utilization of the granzyme-perforin pathway
      of cytotoxic lymphocytes as a cell-to-cell protein delivery module. We designed
      and constructed granzyme B-derived chaperone molecules fused to a fluorescent
      protein payload and expressed these constructs in natural killer (NK) cells.
      Using confocal microscopy and flow cytometry, we investigated the co-localization
      of the chaperones with lytic granules and the chaperone-mediated transfer of the
      fluorescent protein payload from NK to target cells in co-culture experiments. A
      synthetic chaperone consisting of the granzyme B ER signal peptide and a domain
      encompassing putative N-linked glycosylation sites in granzyme B is insufficient
      for payload transfer to target cells, whereas full-length granzyme B is
      sufficient for payload delivery. Combining our functional data with an analysis
      of the crystal structure of granzyme B suggests that the necessary motifs for
      granzyme B loading into lytic granules are dispersed throughout the primary amino
      acid sequence and are only functional when contiguous in the tertiary structure.
      These results illustrate that by using granzyme B as a molecular chaperone the
      granzyme-perforin pathway can be exploited as a programmable molecular delivery
      system for cell-based therapies.

PMID- 29201938
TI  - Classification of images based on small local features: a case applied to
      microaneurysms in fundus retina images.
AB  - Convolutional neural networks (CNNs), the state of the art in image
      classification, have proven to be as effective as an ophthalmologist, when
      detecting referable diabetic retinopathy. Having a size of [Formula: see text] of
      the total image, microaneurysms are early lesions in diabetic retinopathy that
      are difficult to classify. A model that includes two CNNs with different input
      image sizes, [Formula: see text] and [Formula: see text], was developed. These
      models were trained using the Kaggle and Messidor datasets and tested
      independently against the Kaggle dataset, showing a sensitivity [Formula: see
      text], a specificity [Formula: see text], and an area under the receiver
      operating characteristics curve [Formula: see text]. Furthermore, by combining
      these trained models, there was a reduction of false positives for complete
      images by about 50% and a sensitivity of 96% when tested against the DiaRetDB1
      dataset. In addition, a powerful image preprocessing procedure was implemented,
      improving not only images for annotations, but also decreasing the number of
      epochs during training. Finally, a feedback method was developed increasing the
      accuracy of the CNN [Formula: see text] input model.

PMID- 29201939
TI  - Phase-contrast imaging with a compact x-ray light source: system design.
AB  - X-ray phase-contrast imaging (XPCI) overcomes the problem of low contrast between
      different soft tissues achieved in conventional x-ray imaging by introducing x
      ray phase as an additional contrast mechanism. This work describes a compact x
      ray light source (CXLS) and compares, via simulations, the high quality XPCI
      results that can be produced from this source to those produced using a
      microfocus x-ray source. The simulation framework is first validated using an
      image acquired with a microfocus-source, propagation-based XPCI (PB-XPCI) system.
      The phase contrast for a water sphere simulating a simple cyst submersed in
      muscle is evaluated and the evolution of PB-XPCI signal as the object to detector
      distance is increased is demonstrated. The proposed design of a PB-XPCI system
      using the CXLS is described and simulated images of a coronary artery compared
      between CXLS and microfocus source PB-XPCI systems. To generate images with
      similar noise levels, a microfocus source would require a 3000 times longer
      exposure than would the CXLS. We conclude that CXLS technology has the potential
      to provide high-quality XPCI in a medical environment using extremely short
      exposure times relative to microfocus source approaches.

PMID- 29201940
TI  - Assessing computed tomography image quality for combined detection and estimation
      tasks.
AB  - Maintaining or even improving image quality while lowering patient dose is always
      the desire in clinical computed tomography (CT) imaging. Iterative reconstruction
      (IR) algorithms have been designed to allow for a reduced dose while maintaining
      or even improving an image. However, we have previously shown that the dose
      saving capabilities allowed with IR are different for different clinical tasks.
      The channelized scanning linear observer (CSLO) was applied to study clinical
      tasks that combine detection and estimation when assessing CT image data. The
      purpose of this work is to illustrate the importance of task complexity when
      assessing dose savings and to move toward more realistic tasks when performing
      these types of studies. Human-observer validation of these methods will take
      place in a future publication. Low-contrast objects embedded in body-size
      phantoms were imaged multiple times and reconstructed by filtered back projection
      (FBP) and an IR algorithm. The task was to detect, localize, and estimate the
      size and contrast of low-contrast objects in the phantom. Independent signal
      present and signal-absent regions of interest cropped from images were
      channelized by the dense-difference of Gauss channels for CSLO training and
      testing. Estimation receiver operating characteristic (EROC) curves and the areas
      under EROC curves (EAUC) were calculated by CSLO as the figure of merit. The one
      shot method was used to compute the variance of the EAUC values. Results suggest
      that the IR algorithm studied in this work could efficiently reduce the dose by
      [Formula: see text] while maintaining an image quality comparable to conventional
      FBP reconstruction warranting further investigation using real patient data.

PMID- 29201941
TI  - Assessment of a statistical AIF extraction method for dynamic PET studies with
      15O water and 18F fluorodeoxyglucose in locally advanced breast cancer patients.
AB  - Blood flow-metabolism mismatch from dynamic positron emission tomography (PET)
      studies with [Formula: see text]-labeled water ([Formula: see text]) and
      [Formula: see text]-labeled fluorodeoxyglucose (FDG) has been shown to be a
      promising diagnostic for locally advanced breast cancer (LABCa) patients. The
      mismatch measurement involves kinetic analysis with the arterial blood time
      course (AIF) as an input function. We evaluate the use of a statistical method
      for AIF extraction (SAIF) in these studies. Fifty three LABCa patients had
      dynamic PET studies with [Formula: see text] and FDG. For each PET study, two
      AIFs were recovered, an SAIF extraction and also a manual extraction based on a
      region of interest placed over the left ventricle (LV-ROI). Blood flow-metabolism
      mismatch was obtained with each AIF, and kinetic and prognostic reliability
      comparisons were made. Strong correlations were found between kinetic assessments
      produced by both AIFs. SAIF AIFs retained the full prognostic value, for
      pathologic response and overall survival, of LV-ROI AIFs.

PMID- 29201943
TI  - A Factor Analysis of PTSD with Latino Samples with Substance Use Disorders.
AB  - Objective: The Post - Traumatic Stress Disorder (PTSD) factor structure is not a
      generally agreed upon concept. It has remained controversial and its' efficacy
      regarding different trauma presentations is still in question. Therefore, it is
      imperative that we evaluate different conceptualizations of the PTSD factor
      structure. This study aims to understand how PTSD is structured when comorbid
      with Substance Use Disorder (SUD). Method: We evaluated presentations of PTSD -
      SUD from a Latino community based sample. This was done using several accepted
      models of the PTSD factor structure. We then performed an exploratory factor
      analysis of the factor structure of PTSD when comorbid with SUD. Results: We
      found that the factor structure of PTSD - SUD was different from the structure
      presented in the DSM - IV and other empirically validated structural models.
      Conclusion: The factor structure of PTSD may need to include a separate structure
      when PTSD is comorbid with SUD. Cultural differences when structuring the PTSD
      diagnosis should also be considered.

PMID- 29201942
TI  - Dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted
      magnetic resonance imaging for predicting the response of locally advanced breast
      cancer to neoadjuvant therapy: a meta-analysis.
AB  - This meta-analysis assesses the prognostic value of quantitative dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI)
      performed during neoadjuvant therapy (NAT) of locally advanced breast cancer. A
      systematic literature search was conducted to identify studies of quantitative
      DCE-MRI and DW-MRI performed during breast cancer NAT that report the sensitivity
      and specificity for predicting pathological complete response (pCR). Details of
      the study population and imaging parameters were extracted from each study for
      subsequent meta-analysis. Metaregression analysis, subgroup analysis, study
      heterogeneity, and publication bias were assessed. Across 10 studies that met the
      stringent inclusion criteria for this meta-analysis (out of 325 initially
      identified studies), we find that MRI had a pooled sensitivity of 0.91 [95%
      confidence interval (CI), 0.80 to 0.96] and specificity of 0.81(95% CI, 0.68 to
      0.89) when adjusted for covariates. Quantitative DCE-MRI exhibits greater
      specificity for predicting pCR than semiquantitative DCE-MRI ([Formula: see
      text]). Quantitative DCE-MRI and DW-MRI are able to predict, early in the course
      of NAT, the eventual response of breast tumors, with a high level of specificity
      and sensitivity. However, there is a high degree of heterogeneity in published
      studies highlighting the lack of standardization in the field.

PMID- 29201944
TI  - Bystander effects of nitric oxide in anti-tumor photodynamic therapy.
AB  - Ionizing radiation of specifically targeted cells in a given population is known
      to elicit pro-death or pro-survival responses in non-targeted bystander cells,
      which often make no physical contact with the targeted ones. We have recently
      demonstrated a similar phenomenon for non-ionizing photodynamic therapy (PDT),
      showing that prostate cancer cells subjected to targeted photodynamic stress
      stimulated growth and migration of non-stressed, non-contacting bystander cells.
      Diffusible nitric oxide (NO) generated by stress-upregulated inducible nitric
      oxide synthase (iNOS) was shown to play a dominant role in these responses.
      Moreover, target-derived NO stimulated iNOS/NO induction in bystanders,
      suggesting a NO-mediated feed-forward field effect driven by targeted cells
      surviving the photodynamic challenge. In this research highlight, we will review
      these findings and discuss their potential negative implications on clinical PDT
      outcomes and how these might be mitigated through pharmacologic use of select
      iNOS inhibitors.

PMID- 29201945
TI  - The physiology of adolescent sexual behaviour: A systematic review.
AB  - Objectives: To examine physiological influences of adolescent sexual behaviour,
      including associated psychosocial factors. Methods: Systematic review. Results:
      Thirteen studies met the inclusion criteria relating to adolescents, physiology
      and sexual behaviour. We excluded studies relating to abnormal development.
      Findings highlighted hormonal and gender differences. Females appear to be more
      influenced by psychosocial aspects, including the effects of peers, than males.
      Males may be more inclined to engage in unprotected sex with a greater number of
      partners. Early maturing adolescents are more likely to be sexually active at an
      early age. Conclusions: Hormonal, psychosocial context, and sexual preference
      need to be acknowledged in intervention development. Stage of readiness to
      receive information may differ according to gender and physiological maturity.

PMID- 29201946
TI  - Cell-free Fluorescent Intra-Golgi Retrograde Vesicle Trafficking Assay.
AB  - Intra-Golgi retrograde vesicle transport is used to traffic and sort resident
      Golgi enzymes to their appropriate cisternal locations. An assay was established
      to investigate the molecular details of vesicle targeting in a cell-free system.
      Stable cell lines were generated in which the trans-Golgi enzyme
      galactosyltransferase (GalT) was tagged with either CFP or YFP. Given that GalT
      is recycled to the cisterna where it is located at steady state, GalT-containing
      vesicles target GalT-containing cisternal membranes. Golgi membranes were
      therefore isolated from GalT-CFP expressing cells, while vesicles were prepared
      from GalT-YFP expressing ones. Incubating CFP-labelled Golgi with YFP-labelled
      vesicles in the presence of cytosol and an energy regeneration mixture at 37 
      degrees C produced a significant increase in CFP-YFP co-localization upon
      fluorescent imaging of the mixture compared to incubation on ice. The assay was
      validated to require energy, proteins and physiologically important trafficking
      components such as Rab GTPases and the conserved oligomeric Golgi tethering
      complex. This assay is useful for the investigation of both physiological and
      pathological changes that affect the Golgi trafficking machinery, in particular,
      vesicle tethering.

PMID- 29201947
TI  - Older Adults More Likely to Discuss Advance Care Plans With an Attorney Than With
      a Physician.
AB  - Adults are encouraged to discuss their end-of-life health care preferences so
      that their wishes will be known and hopefully honored. The purpose of this study
      was to determine with whom older adults had communicated their future health care
      wishes and the extent to which respondents themselves were serving as a surrogate
      decision maker. Results from the cross-sectional online survey with 294 persons
      aged 50 and older reveal that among the married, over 80% had a discussion with
      their spouse and among those with an adult child, close to two thirds (64%) had.
      Over a third had discussed preferences with an attorney and 23% with a physician.
      Close to half were currently serving as a surrogate decision maker or had been
      asked to and had signed papers to formalize their role. 18% did not think that
      they were a surrogate but were not sure. More education is needed to emphasize
      the importance of advance care planning with a medical professional, especially
      for patients with advanced chronic illness. More education and research about the
      role of surrogate medical decision makers is called for.

PMID- 29201948
TI  - Persistent Diabetes Mellitus Postadrenalectomy in Neonatal McCune-Albright
      Syndrome.

PMID- 29201949
TI  - Prevention Messages in Parent-Infant Bed-Sharing: Message Source, Credibility,
      and Effectiveness.
AB  - Objective. Despite educational outreach, bed-sharing prevalence is rising.
      Mothers' and fathers' bed-sharing practices, prevention message source, perceived
      source credibility, and the effectiveness of the prevention message were
      evaluated. Methods. Data were collected from 678 community parents via an online
      survey. Results were analyzed using descriptive statistics and phi tests.
      Results. Bed-sharing reasons focused on comfort and ease. Mothers were more
      likely to receive prevention messages from individual professionals or
      organizations, whereas fathers were more likely to hear prevention messages from
      spouses/coparents and grandfathers. Physicians were the most common source, and
      physicians and grandmothers were rated as the most credible and effective.
      Conclusions. Prevention message source varies between mothers and fathers,
      highlighting the need for continued research with fathers. Grandmothers and
      physicians are effective and credible sources of prevention messages. Although
      less frequent, prevention messages from grandmothers were most effective. There
      was no evidence of effective messages from educational campaigns.

PMID- 29201950
TI  - Using the Vape Shop Standardized Tobacco Assessment for Retail Settings (V-STARS)
      to Assess Product Availability, Price Promotions, and Messaging in New Hampshire
      Vape Shop Retailers.
AB  - Objectives: This is the first statewide census of the product availability, price
      promotions, and product messaging of vape shops. Methods: A comprehensive list of
      New Hampshire vape shops was developed through a previously validated online
      search method. Store audits were conducted in 55 stores between January and
      February 2016 using the Vape Shop Standardized Tobacco Assessment for Retail
      Settings (V-STARS). Results: Modifiable devices and cig-alikes were sold in 92.6%
      and 14.6% of stores, respectively. Cross-product promotions with tobacco products
      were rare, and messaging promoting e-cigarettes as effective cessation devices
      was found in 27.3% of all stores. Candy/fruit and menthol e-liquids were most
      commonly found in stores, and sampling of products was available in 83.6% of
      stores. Ten (18.2%) stores did not have a minimum age sign posted, and self
      service sampling displays were available in about one-fifth of stores.
      Conclusions: Using V-STARS to conduct retail assessments of vape shops is
      feasible and is important for assessing the changing retail environment of vape
      shops. Vape shops distinguish themselves from traditional tobacco product
      retailers and offer a variety of products to customize a consumer's experience.
      Regulations and effective enforcement ensuring accurate health messages is
      essential.

PMID- 29201951
TI  - Racial-ethnic differences in sexual risk behaviors: The role of substance use.
AB  - This research investigates the impact adolescent substance use has on adult
      sexual risk behaviors within racial-ethnic groups. Previous research has found
      support for this relationship, but often relies on concurrent measures of
      substance use and sexual risk behavior meaning that the causal direction of this
      relationship may be unclear. The data for this study come from the National
      Longitudinal Survey of Adolescent to Adult Health (Add Health), a nationally
      representative survey that followed respondents from adolescence in 1994 to
      adulthood in 2008. Results show that substance use correlates with sexual risk
      behavior, but the impact varies by race-ethnicity.

PMID- 29201952
TI  - An Echocardiography Training Program for Improving the Left Ventricular Function
      Interpretation in Emergency Department; a Brief Report.
AB  - Introduction: Focused training in transthoracic echocardiography enables
      emergency physicians (EPs) to accurately estimate the left ventricular function.
      This study aimed to evaluate the efficacy of a brief training program utilizing
      standardized echocardiography video clips in this regard. Methods: A before and
      after design was used to determine the efficacy of a 1 hour echocardiography
      training program using PowerPoint presentation and standardized echocardiography
      video clips illustrating normal and abnormal left ventricular ejection fraction
      (LVEF) as well as video clips emphasizing the measurement of mitral valve E-point
      septal separation (EPSS). Pre- and post-test evaluation used unique video clips
      and asked trainees to estimate LVEF and EPSS based on the viewed video clips.
      Results: 21 EPs with no prior experience with the echocardiographic technical
      methods completed this study. The EPs had very limited prior echocardiographic
      training. The mean score on the categorization of LVEF estimation improved from
      4.9 (95% CI: 4.1-5.6) to 7.6 (95%CI: 7-8.3) out of a possible 10 score
      (p<0.0001). Categorization of EPSS improved from 4.1 (95% CI: 3.1-5.1) to 8.1
      (95% CI: 7.6- 8.7) after education (p<0.0001). Conclusions: The results of this
      study demonstrate a statistically significant improvement of EPs' ability to
      categorize left ventricular function as normal or depressed, after a short
      lecture utilizing a commercially available DVD of standardized echocardiography
      clips.

PMID- 29201953
TI  - Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case
      Report.
AB  - Warfarin induced skin necrosis (WISN) is a rare but important side effect of
      warfarin. Early diagnosis may lessen the amount of permanent tissue damage and
      can prevent progression to full thickness skin necrosis. So, physicians should be
      aware of such a complication. Screening for protein C or S or anti-thrombin
      deficiencies, or presence of anti-phospholipid antibodies before beginning
      warfarin therapy, could be helpful to avoid high levels of international
      normalized ratio (INR). Here, we report a 54-year-old man who presented to the
      emergency department with acral and penile gangrene following prolonged use of
      warfarin.

PMID- 29201954
TI  - Accuracy of Endoscopy in Predicting the Depth of Mucosal Injury Following Caustic
      Ingestion; a Cross-Sectional Study.
AB  - Introduction: Esophagogastroduodenoscopy (EGD) is currently considered as the
      primary method of determining the degree of mucosal injury following caustic
      ingestion. The present study aimed to evaluate the screening performance
      characteristics of EGD in predicting the depth of gastrointestinal mucosal
      injuries following caustic ingestion. Methods: Adult patients who were referred
      to emergency department due to ingestion of corrosive materials, over a 7-year
      period, were enrolled to this diagnostic accuracy study. Sensitivity,
      specificity, positive and negative predictive values as well as negative and
      positive likelihood ratios of EGD in predicting the depth of mucosal injury was
      calculated using pathologic findings as the gold standard. Results: 54 cases with
      the mean age of 35 +/- 11.2 years were enrolled (59.25% male). Primary endoscopic
      results defined 28 (51.85%) cases as second grade and 26 (48.14%) as third grade
      of mucosal injury. On the other hand, pathologic findings reported 21 (38.88%)
      patients as first grade, 14 (25.92%) as second, and 19 patients (35.18%) as third
      grade. Sensitivity and specificity of endoscopy for determining grade II tissue
      injury were 50.00 (23.04-76.96) and 47.50 (31.51-63.87), respectively. These
      measures were 100.00 (82.35-100) and 80.00 (63.06-91.56), respectively for grade
      III. Accuracy of EGD was 87.03% for grade III and 48.14% for grade II.
      Conclusion: Based on the findings of the present study, endoscopic grading of
      caustic related mucosal injury based on the Zargar's classification has good
      accuracy in predicting grade III (87%) and fail accuracy in grade II injuries
      (48%). It seems that we should be cautious in planning treatment for these
      patients solely based on endoscopic results.

PMID- 29201955
TI  - The Relationship of ST Segment Changes in Lead aVR with Outcomes after Myocardial
      Infarction; a Cross Sectional Study.
AB  - Introduction: Among the 12 leads studied in electrocardiography (ECG), lead aVR
      can be considered as the most forgotten part of it since no attention is paid to
      it as the mirror image of other leads. Therefore, the present study has been
      designed with the aim of evaluating the prevalence of ST segment changes in lead
      aVR and its relationship with the outcome of these patients. Methods: In this
      retrospective cross sectional study medical profiles of patients who had
      presented to emergency department with the final diagnosis of myocardial
      infarction (MI) in a 4-year period were evaluated regarding changes of ST segment
      in lead aVR and its relationship with in-hospital mortality, the number of
      vessels involved, infarct location and cardiac ejection fraction. Results: 288
      patients with the mean age of 59.00 +/- 13.14 (18 - 91) were evaluated (79.2%
      male). 168 (58.3%) patients had the mentioned changes (79.2% male). There was no
      significant relationship between presence of ST changes in lead aVR with infarct
      location (p = 0.976), number of vessels involved (p = 0.269) and ejection
      fraction on admission (p = 0.801). However, ST elevation >= 1 mv in lead aVR had
      a significant relationship with mortality (Odds = 7.72, 95% CI: 3.07 - 19.42, p <
      0.001). Sensitivity, specificity, positive and negative predictive values and
      positive and negative likelihood ratios of ST elevation >= 1 for prediction of in
      hospital mortality were 41.66 (95% CI: 22.79 - 63.05), 91.53 (95% CI: 87.29 -
      94.50), 31.25 (95% CI: 16.74 - 50.13), 94.44 (95% CI: 90.65 - 96.81), 0.45 (95%
      CI: 0.25 - 0.79), and 0.05 (95% CI: 0.03 - 0.09), respectively. Conclusion: Based
      on the results of the present study, the prevalence of ST segment changes in lead
      aVR was estimated to be 58.3%. There was no significant relationship between
      these changes and the number of vessels involved in angiography, infarct location
      and cardiac ejection fraction. However, presence of ST elevation >= 1 in lead aVR
      was associated with 8 times increase in in-hospital mortality risk.

PMID- 29201956
TI  - Traumatic brain injury is unlikely precipitating Leigh syndrome due to the GJB2
      mutation c.35delG.

PMID- 29201957
TI  - Saline Flush versus Chest x ray in Confirmation of Central Venous Catheter
      Placement; a Diagnostic Accuracy Study.
AB  - Introduction: Central venous catheterization (CVC) is a commonly performed
      procedure in critically ill patients of emergency department. This study was
      designed to compare the diagnostic accuracy of saline flush with CXR in
      confirmation of above-the-diaphragm CVC placement. Methods: This prospective
      cross sectional study was conducted on adult patients in need of CVC placement in
      emergency department. Placement Confirmation was performed with saline flush
      method and CXR, then chest computed tomography (CT) was performed as the gold
      standard. The screening performance characteristics of the two methods were
      calculated and compared using SPSS 21 and STATA 11. Results: 103 cases with the
      mean age of 57.18+/-9.3 (35 -80) years were studied (52.4% male). The mean
      duration of procedure was 2.5+/-1.24 in saline flush and 32.11+/-5.52 minutes in
      CXR method (P<0.001(. The area under the ROC curves for saline flush and CXR in
      confirmation of CVC placement were 0.90 (95%CI: 0.70 - 0.100) and 0.80 (95%CI:
      0.55 - 0.100), respectively (p = 0.317). The sensitivity, specificity, positive
      and negative predictive value, and positive and negative likelihood ratio of
      saline flush were 80%, 100%, 100, 98.9%, Infinity, and 0.01, respectively. These
      measures were 60%, 100%, 100%, 98%, Infinity, and 0.02 for CXR, respectively.
      Conclusion: It seems that saline flush method could be considered as a safe,
      rapid, and accurate bedside method for CVC placement confirmation in emergency
      department.

PMID- 29201958
TI  - Perspectives of Patient Handover among Paramedics and Emergency Department
      Members; a Qualitative Study.
AB  - Introduction: Improving patient handover is currently considered as a patient
      safety goal and one of the top five WHO priorities. So, the aim of this study was
      to explore the perspectives of patient handover among paramedics and emergency
      department staff. Methods: This is a descriptive exploratory study with a
      qualitative content analysis approach. Twenty five paramedics and emergency
      department staff were selected through purposeful sampling. The data were
      collected through semi-structured interviews in 2015 and Qualitative Content
      Analysis was used to analyze the data. Result: One main theme and two major
      categories emerged through the data analysis. In general, data analysis indicated
      that patient handover is a sophisticated process, which is an encounter between
      two separate peninsulas with different extrinsic (different environments and
      different equipment) and intrinsic factors (different manpower and different
      expectations). Conclusion: Designing an appropriate environment, providing
      adequate equipment, recruiting appropriate manpower, and clarifying the
      expectations are some strategies for improving patient handover conditions.

PMID- 29201959
TI  - Demographics of Scorpion Sting in Iran; a Cross Sectional Study.
AB  - Introduction: Scorpion sting is an important public health problem in some
      countries, including Iran. This study aimed to describe the demographics of a
      large number of these victims in some endemic areas of Iran. Methods: This cross
      sectional study evaluated baseline characteristics, clinical findings,
      management, and disposition of scorpion stung cases in 26 cities of 4 provinces
      in the southwest quarter of Iran, during one year. Results: 3008 cases of
      scorpion sting with mean age of 27.07 +/- 16.58 years were studied (51.3%
      female). The mean time from sting to hospital was 1.89 +/- 1.04 hours. No first
      aid measures had been taken in 96.6% of cases. Lower (39.5%) and upper (35.7%)
      extremities were stung most frequently. Midnight to 6:00 am was the period of
      time most of stings occurred (34.2%). Local pain (77.2%) and erythema (63.5) were
      among the most common signs and symptoms. 2026 (67.3%) victims had been
      discharged; 326 (10.8%) were admitted or referred to other hospitals and 5 (0.2%)
      cases died. Conclusion: It seems that demographic characteristics of scorpion
      sting in Iran are not so different from those reported from other sites of the
      world, as signs and symptoms of local and systemic envenomations. Victims,
      companions, and healthcare providers perform many futile and maybe harmful
      measures and there is a need to educate all about all of these details.

PMID- 29201960
TI  - Demographics of Fall-Related trauma among the Elderly Presenting to Emergency
      Department; a Cross-Sectional Study.
AB  - Introduction: Falling is reported to be the most common cause of mortality due to
      trauma in individuals over the age of 75 years. The present study is designed
      with the aim of determining the demographics of fall-related trauma among the
      elderly presenting to emergency department (ED). Methods: The present prospective
      cross-sectional study was carried out on all elderly patients >= 60 years old
      presenting to ED of a major referral trauma center in North West of Iran during 1
      year. Demographic data, location and height of falling, duration of
      hospitalization, trauma severity and in-hospital outcome of the patients were
      gathered and reported via descriptive statistics. Results: 228 patients with the
      mean age of 70.96 +/- 5.2 years were studied (53.9% female). Most patients were
      in the 66-70 years age range (32.6%) and had a history of hypertension (22.3%),
      who had visited following a fall inside the house (69.3%), due to slipping
      (73.7%), and from a height equal to or less than 2m (71.9%). 6 (2.6%) patients
      died in the hospital. Mean trauma severity of patients based on ISS, RTS, and
      TRISS were 10.65 +/- 3.95 (3-19), 7.84 +/-.21 (1.4-14.5) and 1.66 +/-1.31 (-1.49
      3.82), respectively. Regarding need for hospitalization, only ISS shows a
      significant difference between outpatients and inpatients (p = 0.023). Patients
      who died had a significantly higher trauma severity based on ISS (p < 0.0001) and
      RTS (p < 0.0001). Conclusion: Based on the findings of the present study,
      slipping and syncope are the most common causes of falling in the studied elderly
      that had mostly happened inside the house and from a height less than 2m.
      Therefore, most patients were in the mild to moderate range of trauma severity.
      ISS and RTS were significantly higher in the 6 (2.6%) patients who died.

PMID- 29201961
TI  - Intranasal Lidocaine for Primary Headache Management in Emergency Department; a
      Clinical Trial.
AB  - Introduction: Most of the headache cases only require pain management in
      emergency department (ED). The present study aimed to evaluate the efficacy of
      intranasal lidocaine in this regard. Method: In this clinical trial, adult
      patients with primary headache were randomly treated with 7.5 mg intravenous (IV)
      chlorpromazine and 1 ml intranasal lidocaine 2% (treatment) or normal saline 0.9%
      (placebo), and were compared 5, 15, and 30 minutes later regarding success rate
      using SPSS 21. Result: 100 patients were assigned to either treatment or placebo
      group. Number needed to treat of intranasal lidocaine at 5, 15, and 30 minutes
      were 4 (95% CI: 2.2 - 6.6), 3 (95% CI: 1.7 - 3.5), and 4 (95% CI: 2.3 - 15.9),
      respectively. These measures for absolute risk reduction were 30 (95% CI: 15.2 -
      44.8), 44 (95% CI: 28.7 - 59.3), and 26 percent (95% CI: 6.3 - 44.3),
      respectively. Pain relapse occurred in 16% of treatment and 11% of control group
      within 1 hour of treatment (p = 0.402). Conclusion: It seems that, intranasal
      lidocaine along with IV chlorpromazine could result in more successful and faster
      management of primary headaches in ED.

PMID- 29201962
TI  - Characteristics of Methadone Intoxicated Children Presenting to Emergency
      Department; a Cross Sectional Study.
AB  - Introduction: Each year a large number of patients present to emergency
      departments (EDs) following accidental or intentional poisoning with methadone.
      This study was designed with the aim of demographic evaluation of methadone
      poisoning in children presenting to ED and proposing preventive measures to
      parents and the healthcare system. Methods: This cross sectional study was
      carried out on children under the age of 12 years presenting to ED of a poisoning
      referral center. Demographic characteristics of the child and parents, cause of
      poisoning, form of drug consumed, dose consumed, the symptoms of the child on
      admission, clinical examination, laboratory findings, and final outcome were
      recorded and reported using descriptive statistics. Results: 179 cases were
      studied (59.2% boys). Cause of consumption was accidental in 175 (97.8%) cases
      and consumed drug dose was unknown in 53 (53.6%) cases. On admission 6 cases were
      in deep coma, 133 (74.3%) had miotic pupils, and 52 (29.1%) were affected with
      respiratory apnea and cyanosis. In 132 (73.8%) cases drugs were obtained from
      unapproved stores and form of drug consumed was syrup in 146 (81.6%) cases. 177
      (98.9%) cases were discharged after 2 or3 days and 2 (1.1%) cases died.
      Conclusion: Based on the results of the present study, most cases of methadone
      poisoning were accidental, in children residing in poor and middle-class areas,
      with parents who had a low level of education and had obtained the drug from
      unapproved stores and stored it in improper containers or at improper places.
      Only 64.8% of the parents were educated regarding drug storage.

PMID- 29201963
TI  - Valsalva maneuver using a Handmade Device in Supraventricular Tachycardia
      Reversion; a Quasi Experimental Study.
AB  - Introduction: The use of vagal nerve stimulation is identified as a proper
      treatment option in patients with stable supraventricular tachycardia (SVT). This
      study aimed to assess the success of Valsalva maneuver via a handmade device in
      reversion of SVT. Methods: In this quasi experimental study, using a handmade
      device, vagus nerve stimulation was performed for SVT patients presenting to
      emergency department or cardiac intervention unit and the success rate and its
      related factors were assessed. Results: 100 patients with the mean age of 53.05
      +/- 13.70 years were studied (67% female). 12 (12%) cases were unable to do the
      maneuver. Out of the 88 (88.0%) patients who could perform the maneuver, 75
      (85.2%) cases were unsuccessful. Dysrhythmia was controlled in 6 (6.8%) cases on
      the first attempt and in 7 (8.0%) cases on the second one (14.8% total success
      rate). 12 of the 13 cases (92.3%) with successful maneuver had history of SVT (p
      = 0.031). There was not any significant association between success rate and sex
      (p = 0.084), age (p = 0.744), or other medical histories (p >= 0.05). Conclusion:
      Based on the results of the present study, the success rate of Valsalva maneuver
      with the mentioned handmade device was calculated to be 14.8%. The only
      independent related factor of successful reversion was SVT history.

PMID- 29201964
TI  - Intravenous Lidocaine Compared to Fentanyl in Renal Colic Pain Management; a
      Randomized Clinical Trial.
AB  - Introduction: Using alpha blockers such as intravenous (IV) lidocaine has been
      deemed effective in controlling acute pain. Therefore, the current study was
      designed with the aim of evaluating the efficiency of IV lidocaine in comparison
      to IV fentanyl in pain management of patients with renal colic in emergency
      department (ED). Methods: In this double blind clinical trial, 18-65 year old
      patients that presented to ED with colicky flank pain and met the inclusion
      criteria of the study were allocated to either lidocaine or fentanyl group using
      block randomization and compared regarding pain severity 5, 10, 15, and 30
      minutes after drug administration. Results: 90 patients with the mean age of
      35.75+/-8.87 years were divided into 2 groups of 45 (90% male). The 2 groups were
      not significantly different regarding the studied baseline variables. Pain
      severity was not significantly different between the 2 groups at various times
      after injection. Treatment failure rate 15 minutes after injection was 44.4% (20
      cases) in IV lidocaine and 17.8% (8 cases) in IV fentanyl group (p = 0.006).
      These rates were 26.6% (12 patients) versus 22.2% 30 minutes after injection (p =
      0.624). Absolute risk increase of treatment failure in case of using lidocaine
      was 26.7 (95% CI: 8.3-44.9) in the 15th minute and 4.4 (95% CI: 13.3-22.2) 30
      minutes after injection. Number needed to harm (NNH) in treatment with lidocaine
      15 and 30 minutes after injection were 4 (95% CI: 2.2-12.0) and 23, respectively.
      Conclusion: Although mean pain severity was not significantly different between
      IV fentanyl and lidocaine at various times after injection, treatment failure
      rate was significantly higher in the IV lidocaine group 15 minutes after
      injection.

PMID- 29201965
TI  - Salivary Chemical Factors in Relation with Oral Cancer in Smokers and Non
      Smokers: a Literature Review.
AB  - Squamous cell carcinoma of oral cavity is of malignant tumors, which causes
      cancerous complications. DNA damage, mainly because of products of oxidative
      stress like reactive oxygen species, is a frequent mutagenic that triggers
      carcinoma. Smoking increases the probability of cancer incidence. Saliva is the
      first biological medium to interact with external compounds, especially smoking
      substances. The present study overviews the salivary level of some remarkable
      compounds in relation with smoking and squamous cell carcinoma. To collect data,
      English literature was searched in databases including PubMed, ScienceDirect and
      Google Scholar. The keywords used for search were as follows: 'Carcinoma,
      Squamous Cell', 'Smoking', 'Saliva', and 'Biomarkers'. The inclusion criteria
      were the presence of salivary chemical factors in relation with oral cancer and
      influence by smoking. Out of 239 found articles, only 56 were selected. Our
      results demonstrated the potential role of salivary biochemistry to predict
      and/or treat complications with cancer in both smoker and non-smoker individuals.
      Changes in concentrations of salivary chemicals including antioxidants, total
      antioxidant, glutathione and uric acid, epithelial growth factor, cytokine
      biomarkers, superoxide dismutase activity, and transcriptome were related to
      squamous cell carcinoma and could be used as potential biomarkers for cancer
      prognosis; moreover, enhancement of antioxidant level might be a potential
      treatment.

PMID- 29201966
TI  - Morphology and Dimensions of Nasopalatine Canal: a Radiographic Analysis Using
      Cone Beam Computed Tomography.
AB  - Statement of the Problem: The surgical procedure of dental implantation in
      anterior maxillary area may be limited by the shape and size of nasopalatine
      canal (NPC). CBCT imaging provides three-dimensional information for surgical
      planning. Purpose: This study is designed to evaluate the anatomy of NPC in a
      selected Iranian population. Materials and Method: In this cross sectional study,
      CBCT images of 301 patients were evaluated for NPC characteristics. Five linear
      measurements including width and length of NPC were performed on reformatted
      sagittal cross sections. The shapes of NPC were also classified in three groups
      according to Bronstein et al. classification in CBCT coronal cross sections. The
      effects of age and gender on measured dimension were assessed. Student's t-test,
      one-way ANOVA/Tukey HSD tests, chi-square and Pearson's correlation coefficient
      were used for statistical analysis. Results: The study comprised 140 males
      (48.5%) and 161 females (53.5%) with mean age of 34.56+/-11.87. The mean length
      of NPC for men and women were 11.46 and 9.37 mm respectively, showing a
      significant statistical difference. Other dimensions of NPC and alveolar bone
      thickness were also greater in men with exception of buccal bone plate width in
      front of Stensen foramen (8.45+/-2.24 vs. 8.52+/-2.03 mm).Most of the cases
      showed Y-shape configuration. The diameter of oral opening of NPC (3.17+/-1.01
      mm) was positively correlated with the patients age (r= 0.138, p= 0.01), while
      buccal bone over the oral opening of NPC (7.05+/-1.38) mm showed negative
      correlation with age (r= -0.199, p= 0.001). Conclusion: All NPC dimensions are
      meaningfully greater in men except for buccal bone plate thickness in front of
      Stensen foramen. The type of canal has no effect on dimensions of the canal.

PMID- 29201967
TI  - Elite Dental Students: a Cross-Sectional Study on Different Aspects of Their Life
      Style.
AB  - Statement of the Problem: Lifestyle has a key role in having a life with quality.
      This is much more critical in academic community. Elite students are the
      scientific capital of each community; therefore, improvement of their life-style
      is a very crucial issue and is a way of esteeming them. Purpose: This study was
      aimed to scrutinize the life-style of elite dental students to provide a
      guideline for healthy life-style for their own and for other students, as well.
      Materials and Method: This descriptive and cross-sectional study was carried out
      on 115 Elite dental students, from a list 175 students, based upon their
      interest. The HPLP-II questionnaire was used which focuses on 6 behavioral
      fields: Spiritual Growth, Interpersonal Relations, Nutrition, Physical Activity,
      Health Responsibility, and Stress Management. The results also compared genders
      and marital status within the study group. The elite dental students were
      categorized in 3 age groups as 19>= yrs (Group I), 20-22 yrs (Group II), and 23<=
      yrs. (Group III) for comparison. Data were analyzed using SPSS version 19,
      independent t-test, one-way ANOVA, and Tukey's test. Results: The mean score of
      the HPLP-II questionnaire was 2.51+/-0.27 (out of score 4). Spiritual growth
      (2.85+/-0.42) and physical activity (2.16+/-0.58) were the highest and the lowest
      scores, respectively. Physical activity was the only subscale different between
      genders (p= 0.000). Marital status had not effect on life-style of students.
      Between the age groups, the physical activity was significantly different between
      group I and II (0.002). Conclusion: Elite dental students' life-style is most
      prominent in spiritual growth and interpersonal relationships dimensions, but is
      the weakest in physical activity and health responsibility behavioral attitudes.
      To improve the talent of all students, interventional workshops/courses aiming at
      modification and promotion of students' lifestyle is recommendable in the
      curriculum.

PMID- 29201968
TI  - Clinicopathologic Study of Intra- Osseous Lesions of the Jaws in Southern Iranian
      Population.
AB  - Statement of the Problem: It is necessary for surgeons and practitioners to know
      about relative incidence and clinicopathologic features of lesions for accurate
      diagnosis and approach of pathologic lesions. Data are limited about overall
      incidence of intra-osseous lesions of the jaws in Iranian patients. Purpose: This
      study evaluated the clinicopathologic features of intra- osseous lesions of the
      jaws in an Iranian population, in a 22-year period. Materials and Method: In this
      cross- sectional retrospective analytical study, 4500 specimens in a 22- year
      period were reviewed. Baseline data of all patients with intra- osseous lesions
      including type and location of lesions as well as patients' age and gender, were
      collected and analyzed by SPSS software using descriptive analysis and Chi-square
      test. Results: There were 1121 (25%) intra-osseous lesion. Odontogenic cysts and
      benign non- odontogenic bone lesions were the most common categories,
      respectively. The mean age of the patients was 30.1+/-16, the total male to
      female ratio was 1.1:1, and the most prevalent location of lesions was posterior
      of mandible. Conclusion: The results showed baseline information of intra-osseous
      lesions that were essentially similar to other populations; however, there were a
      few geographical differences. Further comprehensive studies in other parts of
      country are required to make a more reliable source of reference for clinicians
      and surgeons for evaluating and managing their patients more properly.

PMID- 29201969
TI  - The Effect of Disinfection with Chlorhexidine on the Shear Bond Strength of Equia
      Resin-Modified Glass Ionomer Cement to Dentin in Permanent Teeth after Two
      Thermocycling Protocols.
AB  - Statement of the Problem: There are some concerns regarding the effect of
      chlorhexidine (CHX) applied for cavity disinfection on the bond strength of
      adhesive restorations to dentin. Purpose: This study sought to assess the effect
      of CHX on the shear bond strength (SBS) of Equia resin-modified glass ionomer
      cement (RMGIC) to dentin in permanent teeth. Materials and Method: In this
      experimental study, the buccal surface of 84 freshly extracted human premolars
      was ground to expose the flat dentin. The samples were randomly assigned to four
      groups (n=21). The steps were as following in the group Ia: conditioning, Equia
      RMGIC, 500 thermal cycles; group Ib: conditioning, Equia RMGIC, 6000 thermal
      cycles; group IIa: conditioning, CHX, Equia RMGIC, 500 thermal cycles, and group
      IIb: conditioning, CHX, Equia RMGIC, and 6000 thermal cycles. Twenty samples from
      each group were subjected to SBS test and one sample was inspected under a
      scanning electron microscope. Data were analyzed using two-way ANOVA and t-test.
      Results: The SBS was significantly different among the groups (p= 0.007). The
      groups subjected to 500 thermal cycles showed significantly higher SBS to dentin
      when they were treated with CHX (p= 0.000). There was no significant difference
      between samples thermocycled for 6000 cycles with and without application of CHX
      (p= 0.269). The SBS in the groups that were thermocycled for 6000 cycles (Ib and
      IIb) was lower than those thermocycled for 500 cycles (Ia and IIa). This
      difference between IIa and IIb was statistically significant (p= 0.007).
      Conclusion: Chlorhexidine can positively affect the short term SBS of Equia RMGIC
      to dentin.

PMID- 29201970
TI  - Comparison of the Marginal Bone Loss in One-stage versus Two-stage Implant
      Surgery.
AB  - Statement of the Problem: Dental implant is one of the best choices for
      reconstruction of aesthetic and function. High success rate of these treatments
      are related to some considerations such as case selection, implant system
      selection and surgical methods. One-stage or two-stage surgical approaches are
      routine surgical methods in dental implant treatments. The minimum rate of bone
      loss around fixtures is the most important criteria for evaluation of implant
      treatment success that can be affected by different methods of surgery. Purpose:
      This experimental study has been done to compare the crestal bone loss at mesial
      and distal surface of implants installed through either one-stage or two-stage
      surgical approach. Materials and Method: In the present randomized clinical
      trial, 310 Astra Tech implant system were divided into two unequal groups to be
      used for 140 patients. One hundred and seventy implants were inserted through one
      stage and 140 through two-stage surgical approach. The baseline parallel
      periapical radiography was provided immediately after the surgery. Six months
      after the functional loading, another radiographic image was provided by using
      the same technique and machine. Marginal bone loss was calculated by using Adobe
      Photoshop CS5 software. Data were statistically analyzed with SPSS software. p
      values less than 0.05 were considered as significant. Results: The mean Bone loss
      on the mesial and distal surfaces of implants inserted through one-stage surgery
      and two-stage surgery was 0.76+/-0.04 and 0.842+/-0.04 mm respectively. No
      notable marginal bone change was observed between the maxilla (0.860mm) and
      mandible (0.729mm). Moreover, p Value was>0.05 in all samples, indicating no
      significant difference in the crestal bone loss. Conclusion: Accordingly, one
      stage surgical technique may provide better esthetic and function for dental
      implants. There is no significant difference between the two approaches
      concerning the marginal bone loss.

PMID- 29201971
TI  - The Effect of Autoclave Sterilization on Resistance to Cyclic Fatigue of Hero
      Endodontic File #642 (6%) at Two Artificial Curvature.
AB  - Statement of the Problem: File fracture can interfere with cleaning and shaping
      of the canal and compromise periradicular healing. Autoclave sterilization may
      prone the files to fracture. Purpose: The purpose of the present study was to
      determine the effect of autoclave sterilization on the cyclic fatigue resistance
      of Hero642 rotary instrument in two curvatures of 45 and 60 degrees. Materials
      and Method: For this experimental in-vitro study, 90 Nickel-Titanium HERO 642
      rotary files #30 with 0.06 taper were selected. They were divided into two groups
      (curvature of 45 and 60 degree) of 45 files. Each group was then subdivided into
      3 subgroups; group I: no sterilization, group II: 5 cycles of sterilization and
      group III: 10 cycles of sterilization. Files were used in artificial canals until
      fracture. The cyclic fatigue was measured as the number of cycles before
      fracture. The data was statically analyzed by Student's t-test and two-way
      analysis of variance. Results: There was a significant difference in cyclic
      fatigue of two curvature of 45 and 60 degrees (p= 0.001). However, sterilization
      process has no significant effect on cyclic fatigue of HERO files (p= 0.557).
      Conclusion: Sterilization had no effect on the cyclic fatigue of HERO 642 files
      when used in curvature of 45 or 60 degrees.

PMID- 29201972
TI  - A Survey of Knowledge, Attitude and Practice of Iranian Dentists and Pedodontists
      in Relation to Child Abuse.
AB  - Statement of the Problem: Since almost half of the child abuse cases affect the
      head and neck region, dentists have an important role in the diagnosis and report
      of oral and dental aspects of child abuse cases. Purpose: The objective of the
      current study was to evaluate the knowledge, attitude and practice of the general
      dentists and pedodontists regarding child abuse and child neglect. Materials and
      Method: This cross-sectional study was carried out on the participants of the
      12th congress of pedodontists of Iran. A self-administered questionnaire was used
      for evaluating their knowledge, attitude and practice toward child abuse. T-test
      and ANOVA were applied to analyze the data by SPSS software. p <0.05 was
      considered statistically significant. Results: The mean score of knowledge,
      attitude and practice of the participants regarding child abuse was 10.24+/-2.68,
      41.54+/-11.24 and 2.78+/-1.05, respectively. The knowledge of pedodontists was
      significantly higher than knowledge of general dentists. No statistically
      significant difference was observed in attitude and practice (p> 0.05).
      Conclusion: Dentists had a moderate knowledge, poor attitude and moderate
      practice regarding child abuse. Considering this fact, improvements in child
      abuse education for undergraduate students and continuing post-graduate training
      in this field are recommended.

PMID- 29201973
TI  - The Accuracy of Four Impression-making Techniques in Angulated Implants Based on
      Vertical Gap.
AB  - Statement of the Problem: Precision of the impression taken from implant
      positions significantly determines accurate fit of implant-supported prostheses.
      An imprecise impression may produce prosthesis misfit. Purpose: This study aimed
      to evaluate the accuracy of four impression-making techniques for angulated
      implants by stereomicroscope through measuring the vertical marginal gaps between
      the cemented metal framework and the implant analog. Materials and Method: A
      definitive cast with two 15 degrees  mesially angulated implants served as the
      standard reference for making all the impressions and later for accuracy
      evaluation. Four groups of five samples were evaluated: (1) closed-tray snap-fit
      transfer, (2) open-tray nonsplinted impression coping, (3) metal splinted
      impression coping, and (4) fabricated acrylic resin transfer cap. A gold
      palladium framework was fabricated over the angulated implant abutments, the fit
      of which was used as reference. The gaps between the metal framework and the
      implant analogs were measured in sample groups. Corresponding means for each
      technique and the definitive cast were compared by using ANOVA and post hoc
      tests. Results: The mean marginal gap was 38.16+/-0um in definitive cast, 89+/
      19.74um in group 1, 78.66+/-20.63um in group 2, 54.16+/-24.29um in group 3, and
      55.83+/-18.30um in group 4. ANOVA revealed significant differences between the
      definitive cast and groups 1 and 2, but not with groups 3 and 4 (p< 0.05).
      Conclusion: Vertical gap measurements showed that metal splinted impression
      coping and fabricated acrylic resin transfer cap techniques produced quite more
      accurate impressions than closed-tray snap-fit transfer and open-tray nonsplinted
      impression coping techniques do. The fabricated acrylic resin transfer cap
      technique seems to be a reliable impression-making method.

PMID- 29201974
TI  - The Risk Factors in Early Failure of Dental Implants: a Retrospective Study.
AB  - Statement of the Problem: Despite the low failure rate of dental implants,
      recognition of the risk factors can enhance the predictability of failure.
      Purpose: The aim of this study was to evaluate the risk factors for early implant
      failure. Materials and Method: This retrospective cohort study was conducted on
      two groups of patients, the patients with a failed implant before loading and
      those without a failed implant. Age, gender, implant type, implant surface,
      implant length, bone type, type of surgery (one- or two-stage) and immediate
      (fresh socket) or delayed placement of implant were the variables to be assessed
      in this study. Results: Out of the 1,093 evaluated implants, 73 cases (6.68%)
      failed in early stages. The two groups were significantly different in terms of
      implant surface, fresh socket placement, prophylactic use of antibiotics, and
      bone density (p< 0.05). Age, gender, implant height, implant type (cylindrical or
      tapered) and one-stage or two-stage placement were not significantly different
      between the two groups (p> 0.05). Conclusion: It seems that prophylactic
      antibiotic therapy, implant surface, bone density and placement in fresh
      extraction socket may contribute to dental implant failure.

PMID- 29201975
TI  - Angulated Implants for Fabrication of Implant Supported Fixed Partial Denture in
      the Maxilla.
AB  - Until recently, angled abutments have been the only solution to correcting the
      trajectory of the emergence profile of labially inclined implants in the maxilla.
      However, the clinical implications of angled abutments reveal several
      shortcomings. Newly designed angulated implants with a 12-degree restorative
      platform angulation are an alternative to angled abutments. The purpose of this
      article was to report a case utilizing new angulated implants (Co-axis, Keystone
      dental, Burlington, MA, USA) in the premaxilla thereby facilitating fabrication
      of a multi-unit implant retained fixed dental prosthesis.

PMID- 29201976
TI  - Palisaded Encapsulated (Solitary Circumscribed) Neuroma of the Buccal Mucosa: a
      Rare Case.
AB  - The rarity of oral soft tissue spindle cell tumors combined with overlapping
      microscopic patterns can make challenges in their diagnosis and treatment. Oral
      cavity palisaded encapsulated neuroma is an uncommon lesion which occurs often on
      the hard palate. It is essential for oral pathologists to be familiar with its
      histopathology of this lesion is essential since many lesions are probably
      diagnosed microscopically as neurofibroma or schwannoma. Here, we report a case
      of oral palisaded encapsulated (solitary circumscribed) neuroma in an unusual
      site.

PMID- 29201977
TI  - Mixed Emotions Within the Context of Goal Pursuit.
AB  - Development in adulthood occurs through the process of setting and working toward
      goals. Emotions link experiences to goals and action, and as such are integral to
      goal setting, evaluation of goal progress, and goal pursuit. When viewed in the
      context of goals, the simultaneous experience of positive and negative or "mixed"
      emotions coheres with the complexity of goal pursuit within the context of
      competing demands in daily life. Mixed emotions may be experienced as uncertainty
      in which goal to prioritize, ambiguity in whether an event served or impeded goal
      progress, or poignancy in a bittersweet moment of recognizing the losses that
      accompany gains. Mixed emotions therefore represent a problem that must be
      resolved-through either prioritization of conflicting goals, down-playing
      negative affective response, or goal disengagement-before goal pursuit can
      continue. Because mixed emotions must be resolved before they can be translated
      to action, the experience of mixed emotions may evoke a new awareness of
      priorities and available options that leads to better goal outcomes. Over time,
      openness to mixed emotions could result in outcomes such as better health and
      self-actualization.

PMID- 29201978
TI  - Power analysis data set for 4-Bit MOCLA adder.
AB  - In order to reduce the silicon area of the chip and optimize the power of
      arithmetic circuits, this paper proposes a low power carry look-ahead BCD (Binary
      Coded Decimal) adder which uses a four bit MOCLA (Multiplexer and Or gate based
      Carry Look Ahead Adder) that forms the basic building block. This proposed MOCLA
      style uses a 2 input MUX, OR gate and GDI (Gate Diffusion Input) based full adder
      and PG units and it is used for achieving low power in BCD adder circuits.

PMID- 29201979
TI  - Quantitative evaluation of pregnant women delivery status' records in Akure,
      Nigeria.
AB  - In this data article, monthly records (datasets) of total delivery, normal
      delivery, delivery through Caesarean section and number of still births from
      pregnant women in Akure, the capital city of Ondo state Nigeria, for a period of
      ten years, between January 2007 and December 2016 were considered. Correlational
      and time series analyses were conducted on the monthly records of total delivery,
      normal delivery (delivery through woman virginal), delivery through Caesarean
      section, and number of still births, in order to observe the patterns each of
      these indicators follows and to recommend appropriate model for forecasting their
      future values. The data were obtained in raw form from State Specialist Hospital
      (SSH), Akure, Ondo state, Nigeria. A clear description and variation in each of
      these indicators (total delivery, normal delivery, caesarean section, and still
      births) were considered separately using descriptive statistics and box plots.
      Different models were also proposed for each of these indicators using time
      series models.

PMID- 29201980
TI  - Experimental data of co-crystals of Etravirine and L-tartaric acid.
AB  - Etravirine is a drug used alongside other medication in the treatment of HIV and
      is a non-nucleoside reverse transcriptase inhibitor. It is a BCS class IV drug,
      having low solubility and high permeability (Drugbank,
      https://www.drugbank.ca/drugs/DB06414) [1]. As a result, large doses of the drug
      are required for treatment. Two pills have to be taken twice a day, making it a
      "pill burden" (Intelence, http://www.intelence.com/hcp/dosing/administration
      options) [2]. Therefore, attempts of co-crystallizing Etravirine are attractive
      as the solubility of the drug tends to increase in this solid form (Schultheiss
      and Newman, 2009) [3]. In this study Etravirine co-crystals were synthesized in
      the molar ratios 1:1, 1:2 and 2:1 with L-tartaric acid as the co-former. Both
      slow evaporation and physical mixture was performed to mix the components. DSC
      values of final products are presented as well as FTIR spectra to observe the
      altered intermolecular interactions. A chemical stability test was performed
      after seven days using area under curve data from an HPLC instrument.

PMID- 29201981
TI  - Data on the optimized sulphate electrolyte zinc rich coating produced through in
      situ variation of process parameters.
AB  - In this study, a comprehensive effect of particle loading and optimised process
      parameter on the developed zinc electrolyte was presented. The depositions were
      performed between 10-30 min at a stirring rate of 200 rpm at room temperature of
      30  degrees C. The effect of coating difference on the properties and interfacial
      surface was acquired, at a voltage interval between 0.6 and 1.0 V for the coating
      duration. The framework of bath condition as it influences the coating thickness
      was put into consideration. Hence, the electrodeposition data for coating
      thickness, and coating per unit area at constant distance between the anode and
      cathode with depth of immersion were acquired. The weight gained under varying
      coating parameter were acquired and could be used for designing and given typical
      direction to multifunctional performance of developed multifacetal coatings in
      surface engineering application.

PMID- 29201982
TI  - Dataset of the HOX1 gene sequences of the wheat polyploids and their diploid
      relatives.
AB  - The TaHOX-1 gene of common wheat Triticum aestivum L. (BAD-genome) encodes
      transcription factor (HD-Zip I) which is characterized by the presence of a DNA
      binding homeodomain (HD) with an adjacent Leucine zipper (LZ) motif. This gene
      can play a role in adapting plant to a variety of abiotic stresses, such as
      drought, cold, salinity etc., which strongly affect wheat production. However,
      it's both functional role in stress resistance and divergence during wheat
      evolution has not yet been elucidated. This data in brief article is associated
      with the research paper "Structural and functional divergence of homoeologous
      copies of the TaHOX-1 gene in polyploid wheats and their diploid ancestors". The
      data set represents a recent survey of the primary HOX-1 gene sequences isolated
      from the first wheat allotetraploids (BA-genome) and their corresponding Triticum
      and Aegilops diploid relatives. Specifically, we provide detailed information
      about the HOX-1 nucleotide sequences of the promoter region and both nucleotide
      and amino acid sequences of the gene. The sequencing data used here is available
      at DDBJ/EMBL/GenBank under the accession numbers MG000630-MG000698.

PMID- 29201983
TI  - Data on novel DNA methylation changes induced by valproic acid in human
      hepatocytes.
AB  - Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world.
      Despite its pharmacological importance, it may cause liver toxicity and
      steatosis. However the exact mechanism of the steatosis formation is unknown. The
      data presented in this DIB publication is used to further investigate the VPA
      induced mechanisms of steatosis by analyzing changes in patterns of methylation.
      Therefore, primary human hepatocytes (PHHs) were exposed to VPA at a
      concentration which was shown to cause steatosis without inducing overt
      cytotoxicity. VPA was administered for 5 days daily to PHHs. Furthermore, after 5
      days VPA-treatment parts of the PHHs were followed for a 3 days washout.
      Differentially methylated DNA regions (DMRs) were identified by using the
      'Methylated DNA Immuno-Precipitation - sequencing' (MeDIP-seq) method. The data
      presented in this DIB demonstrate induced steatosis pathways by all DMRs during
      VPA-treatment, covering interesting drug-induced steatosis genes (persistent DMRs
      upon terminating VPA treatment and the EP300 network). This was illustrated in
      our associated article (Wolters et al., 2017) [1]. MeDIP-seq raw data are
      available on ArrayExpress (accession number: E-MTAB-4437).

PMID- 29201984
TI  - Genome statistics and phylogenetic reconstructions for Southern Hemisphere whelks
      (Gastropoda: Buccinulidae).
AB  - This data article provides genome statistics, phylogenetic networks and trees for
      a phylogenetic study of Southern Hemisphere Buccinulidae marine snails [1]. We
      present alternative phylogenetic reconstructions using mitochondrial genomic and
      45S nuclear ribosomal cassette DNA sequence data, as well as trees based on short
      length DNA sequence data. We also investigate the proportion of variable sites
      per sequence length for a set of mitochondrial and nuclear ribosomal genes, in
      order to examine the phylogenetic information provided by different DNA markers.
      Sequence alignment files used for phylogenetic reconstructions in the main text
      and this article are provided here.

PMID- 29201985
TI  - Assessment of groundwater quality and evaluation of scaling and corrosiveness
      potential of drinking water samples in villages of Chabahr city, Sistan and
      Baluchistan province in Iran.
AB  - The aims of this study were to assess and analysis of drinking water quality of
      Chabahar villages in Sistan and Baluchistan province by water quality index (WQI)
      and to investigate the water stability in subjected area. The results illustrated
      that the average values of LSI, RSI, PSI, LS, and AI was 0.5 (+/-0.34), 6.76 (+/
      0.6), 6.50 (+/-0.99), 2.71 (+/-1.59), and 12.63 (+/-0.34), respectively. The
      calculation of WQI for groundwater samples indicated that 25% of the samples
      could be considered as excellent water, 50% of the samples were classified as
      good water category and 25% of the samples showed poor water category.

PMID- 29201986
TI  - Data describing the accuracy of non-numerical visual features in predicting fMRI
      responses to numerosity.
AB  - Here we took several stimulus configurations that have the same numerosity
      progression but vary considerably in their non-numerical visual features. We
      collected responses to these stimuli using ultra-high-field (7T) fMRI in a
      posterior parietal area that responds to changes in these stimuli. We first
      quantify the relationships between numerosity and several non-numerical visual
      features in each stimulus configuration. We then use population receptive field
      (pRF) modeling to quantify how well responses to each of these visual features
      predicts the observed responses to each stimulus configuration, and observed
      responses to all stimulus configurations together. We compare the predictive
      accuracy of responses to numerosity and to non-numerical visual features in
      explaining the observed responses. This provides the details of the analysis
      outcomes summarized in an accompanying article (10.1016/j.neuroimage.2017.02.012,
      NIMG-16-1350).

PMID- 29201987
TI  - Axillary lymph node metastasis in ovarian carcinoma: Two case reports and review
      of literature.
AB  - *Extra-peritoneal metastasis is uncommon in epithelial ovarian
      carcinoma.*Metastasis of epithelial ovarian carcinoma to axillary lymph node is
      rare.*Lymphatic drainage system can explain the rout of this distant
      metastasis.*Tissue diagnosis is the mainstay in identifying the origin of
      axillary metastasis.

PMID- 29201988
TI  - Solitary fibrous tumor of the vulva resulting in spinal metastasis: A case
      report.
AB  - *Solitary fibrous tumors are typically indolent tumors of the pleura.*Primary
      origin in the female reproductive organs is rare, as are aggressive forms.*We
      report a case of a vulvar solitary fibrous tumor, notable for extensive spinal
      metastasis.

PMID- 29201989
TI  - Geographic disparities in the distribution of the U.S. gynecologic oncology
      workforce: A Society of Gynecologic Oncology study.
AB  - A recent ASCO workforce study projects a significant shortage of oncologists in
      the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study
      aim was to determine the patterns of distribution of U.S. gynecologic oncologists
      (GO) and to identify provider-based attitudes and barriers that may prevent GOs
      from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited
      to participate in an on-line survey regarding geographic distribution and
      participation in outreach care. A total of 320 GOs (43%) responded; median age
      range was 35-45 years and 57% were male. Most practiced in an urban setting (72%)
      at a university hospital (43%). Only 13% of GOs practiced in an area with a
      population < 50,000. A desire to remain in academics and exposure to senior-level
      mentorship were the factors most influencing initial practice location.
      Approximately 50% believed geographic disparities exist in GO workforce
      distribution that pose access barriers to care; however, 39% "strongly agreed"
      that cancer patients who live in R/US regions should travel to urban cancer
      centers to receive care within a center of excellence model. GOs who practice
      within 50 miles of only 0-5 other GOs were more likely to provide R/US care
      compared to those practicing within 50 miles of >= 10 GOs (p < 0.0001). Most
      (39%) believed the major barriers to providing cancer care in R/US areas were
      volume and systems-based. Most also believed the best solution was a hybrid
      approach, with coordination of local and centralized cancer care services. Among
      GOs, a self-reported rural-urban disparity exists in the density of gynecologic
      oncologists. These study findings may help address barriers to providing cancer
      care in R/US practice environments.

PMID- 29201990
TI  - Retinal thickness correlates with parietal cortical atrophy in early-onset
      Alzheimer's disease and controls.
AB  - Introduction: The retina may reflect Alzheimer's disease (AD) neuropathological
      changes and is easily visualized with optical coherence tomography (OCT). Retinal
      thickness decrease has been correlated to AD, however, without information on
      amyloid status. We correlated retinal (layer) thickness to AD biomarkers in
      amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls.
      Methods: We measured macular thickness and peripapillary retinal nerve fiber
      layer thickness with OCT in 15 EOAD patients and 15 controls and correlated
      retinal thickness to visual rating scores for atrophy on magnetic resonance
      imaging. Results: Total macular thickness correlated to parietal cortical atrophy
      in both groups (Spearman rho -0.603, P = .001). Macular and peripapillary retinal
      nerve fiber layer thicknesses were not significantly decreased in EOAD compared
      to controls. Discussion: Retinal thickness does not discriminate EOAD from
      controls but is correlated to parietal cortical atrophy in both groups. These
      findings may suggest reflection of cerebral cortical changes in the retina,
      independent of amyloid.

PMID- 29201991
TI  - White matter signal abnormalities in former National Football League players.
AB  - Introduction: Later-life brain alterations in former tackle football players are
      poorly understood, particularly regarding their relationship with repetitive head
      impacts (RHIs) and clinical function. We examined white matter signal
      abnormalities (WMSAs) and their association with RHIs and clinical function in
      former National Football League (NFL) players. Methods: Eighty-six clinically
      symptomatic former NFL players and 23 same-age reportedly asymptomatic controls
      without head trauma exposure underwent magnetic resonance imaging and
      neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact
      index quantified RHIs. Results: In former NFL players, increased volume of WMSAs
      was associated with higher cumulative head impact index scores (P = .043) and
      worse psychomotor speed and executive function (P = .015). Although former NFL
      players had greater WMSA volume than controls (P = .046), these findings are
      inconclusive due to recruitment of controls based on lack of clinical symptoms
      and head trauma exposure. Discussion: In former NFL players, WMSAs may reflect
      long-term microvascular and nonmicrovascular pathologies from RHIs that
      negatively impact cognition.

PMID- 29201992
TI  - Probability of Alzheimer's disease in breast cancer survivors based on gray
      matter structural network efficiency.
AB  - Introduction: Breast cancer chemotherapy is associated with accelerated aging and
      potentially increased risk for Alzheimer's disease (AD). Methods: We calculated
      the probability of AD diagnosis from brain network and demographic and genetic
      data obtained from 47 female AD converters and 47 matched healthy controls. We
      then applied this algorithm to data from 78 breast cancer survivors. Results: The
      classifier discriminated between AD and healthy controls with 86% accuracy (P <
      .0001). Chemotherapy-treated breast cancer survivors demonstrated significantly
      higher probability of AD compared to healthy controls (P < .0001) and
      chemotherapy-naive survivors (P = .007), even after stratifying for
      apolipoprotein e4 genotype. Chemotherapy-naive survivors also showed higher AD
      probability compared to healthy controls (P = .014). Discussion: Chemotherapy
      treated breast cancer survivors who have a particular profile of brain structure
      may have a higher risk for AD, especially those who are older and have lower
      cognitive reserve.

PMID- 29201993
TI  - Traumatic exposures, posttraumatic stress disorder, and cognitive functioning in
      World Trade Center responders.
AB  - Introduction: This study examined whether World Trade Center (WTC)-related
      exposures and posttraumatic stress disorder (PTSD) were associated with cognitive
      function and whether WTC responders' cognition differed from normative data.
      Methods: A computer-assisted neuropsychological battery was administered to a
      prospective cohort study of 1193 WTC responders with no history of stroke or WTC
      related head injuries. Data were linked to information collected prospectively
      since 2002. Sample averages were compared to published norms. Results:
      Approximately 14.8% of sampled responders had cognitive dysfunction. WTC
      responders had worse cognitive function compared to normative data. PTSD symptom
      severity and working >5 weeks on-site was associated with lower cognition.
      Discussion: Results from this sample highlight the potential for WTC responders
      to be experiencing an increased burden of cognitive dysfunction and linked
      lowered cognitive functioning to physical exposures and to PTSD. Future research
      is warranted to understand the extent to which cognitive dysfunction is evident
      in neural dysfunction.

PMID- 29201994
TI  - Speed of processing training results in lower risk of dementia.
AB  - Introduction: Cognitive training improves cognitive performance and delays
      functional impairment, but its effects on dementia are not known. We examined
      whether three different types of cognitive training lowered the risk of dementia
      across 10 years of follow-up relative to control and if greater number of
      training sessions attended was associated with lower dementia risk. Methods: The
      Advanced Cognitive Training in Vital Elderly (NCT00298558) study was a randomized
      controlled trial (N = 2802) among initially healthy older adults, which examined
      the efficacy of three cognitive training programs (memory, reasoning, or speed of
      processing) relative to a no-contact control condition. Up to 10 training
      sessions were delivered over 6 weeks with up to four sessions of booster training
      delivered at 11 months and a second set of up to four booster sessions at 35
      months. Outcome assessments were taken immediately after intervention and at
      intervals over 10 years. Dementia was defined using a combination of interview-
      and performance-based methods. Results: A total of 260 cases of dementia were
      identified during the follow-up. Speed training resulted in reduced risk of
      dementia (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50-0.998, P =
      .049) compared to control, but memory and reasoning training did not (HR 0.79,
      95% CI 0.57-1.11, P = .177 and HR 0.79, 95% CI 0.56-1.10, P = .163,
      respectively). Each additional speed training session was associated with a 10%
      lower hazard for dementia (unadjusted HR, 0.90; 95% CI, 0.85-0.95, P < .001).
      Discussion: Initially, healthy older adults randomized to speed of processing
      cognitive training had a 29% reduction in their risk of dementia after 10 years
      of follow-up compared to the untreated control group.

PMID- 29201995
TI  - Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis
      patients.
AB  - Introduction: Rheumatoid arthritis is a systemic inflammatory disease, and
      classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy.
      It is unknown what impact cDMARDs might have on dementia as an outcome. Methods:
      Incident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to
      2011 were identified from the UK Clinical Practice Research Datalink. There were
      3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide
      range of confounders. Impact on dementia was assessed using survival models.
      Results: cDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95%
      confidence interval: 0.42-0.85). The effect was strongest in methotrexate users
      (hazard ratio: 0.52; 95% confidence interval; 0.34-0.82). Discussion: The strong
      effect of cDMARD use on halving of dementia risk requires replication in a trial
      and may provide an important therapeutic pharmacological treatment.

PMID- 29201996
TI  - A randomized, exploratory molecular imaging study targeting amyloid beta with a
      novel 8-OH quinoline in Alzheimer's disease: The PBT2-204 IMAGINE study.
AB  - Introduction: We are developing a second generation 8-OH quinoline (2
      (dimethylamino) methyl-5, 7-dichloro-8-hydroxyquinoline [PBT2, Prana
      Biotechnology]) for targeting amyloid beta (Abeta) in Alzheimer's disease (AD).
      In an earlier phase IIa, 3 month trial, PBT2 lowered cerebrospinal fluid Abeta by
      13% and improved cognition (executive function) in a dose-related fashion in
      early AD. We, therefore, sought to learn whether PBT2 could alter the Abeta-PET
      signal in subjects with prodromal or mild AD, in an exploratory randomized study
      over a 12-month phase in a double-blind and a 12-month open label extension phase
      trial design. Methods: For inclusion, the usual clinical criteria for prodromal
      or probable AD, Mini-Mental State Examination >=20, and global Pittsburgh
      compound B (PiB)-PET standardized uptake volume ratio (SUVR) >1.7 were used. As
      this was an exploratory study, we included contemporaneous matched control data
      from the Australian Imaging Biomarker and Lifestyle Study (AIBL). Other measures
      included fluorodeoxyglucose-positron emission tomography, magnetic resonance
      imaging volumetrics, blood Abeta biomarkers, and cognition and function. Results:
      Forty subjects completed the first 12-month double-blind phase (placebo = 15,
      PBT2 = 25), and 27 subjects completed the 12-month open label extension phase
      (placebo = 11, PBT2 = 16). Overall, PTB2 250 mg/day was safe and well tolerated.
      The mean PiB-PET SUVR at baseline was 2.51 +/- 0.59. After adjusting for baseline
      SUVR, in the double-blind phase, the placebo group showed a nonsignificant
      decline in PiB-PET SUVR, whereas the PBT2 group declined significantly (P =
      .048). Subjects who did not enter or complete the extension study had a
      significantly higher 12-month Abeta-PET SUVR (2.68 +/- 0.55) compared with those
      who completed (2.29 +/- 0.48). Both groups differed significantly from the rate
      of change over 12 months in the AIBL control group. In the open label 12-month
      extension study, the PiB-SUVR stabilized. There were no significant differences
      between PBT2 and controls in fluorodeoxyglucose-positron emission tomography,
      magnetic resonance imaging volumetrics, blood Abeta biomarkers, or
      cognition/function over the course of the double-blind phase. Discussion: There
      was no significant difference between PBT2 and controls at 12 months, likely due
      to the large individual variances over a relatively small number of subjects.
      PBT2 was associated with a significant 3% PiB-PET SUVR decline in the double
      blind phase and a stabilization of SUVR in the open-label phase. From this
      exploratory study, we have learned that the entry criterion of SUVR should have
      been set at >= 1.5 and <2.0, where we know from the AIBL study that subjects in
      this band are accumulating Abeta in a linear fashion and that subjects who
      withdrew from this type of study have much higher SUVRs, which if not taken into
      account, could distort the final results. Because of large individual variations
      in SUVR, future studies of PBT2 will require larger numbers of subjects (n > 90
      per arm) over a longer period (18 months or more). Further evaluation of higher
      doses of PBT2 in earlier stages of AD is warranted. Trial Registration: ACTRN
      12611001008910 and ACTRN 12613000777796.

PMID- 29201997
TI  - Cardiac rehabilitation in patients with cardiovascular disease leads various
      hemodynamic parameters obtained using simple non-invasive tests to their
      appropriate levels.
AB  - We evaluated whether comprehensive cardiac rehabilitation (CR) in patients with
      cardiovascular disease (CVD) could improve various hemodynamic parameters
      obtained using simple non-invasive tests. We analyzed 48 CVD patients with (n =
      38, CR group) or without (n = 10, non-CR group) a CR program, and prospectively
      followed them for 12 months. Various parameters were measured at baseline and
      after 12 months using 3 simple non-invasive tests: blood pressure (BP) and
      severity of atherosclerosis [arterial velocity pulse index (AVI) and atrial
      pressure volume index] were determined using PASESA(r), an index of total
      autonomic nerve activity and a coefficient of variation of the R-R interval
      (CVRR) were determined using eHEART(r), and the total peripheral resistance,
      stroke volume and cardiac index (CI) were determined using nico(r). The main
      hemodynamic parameters did not change between baseline and 12 months in both
      groups. Patients in the CR group were divided into higher (H-) and lower (L-)
      systolic BP (SBP) or AVI according to the average value of SBP or AVI at baseline
      in the CR group. Patients with H-SBP or H-AVI in the CR group showed a
      significant reduction of SBP or AVI at 12 months. In addition, patients in the CR
      group were divided into H- and L- CI or CVRR according to the average value of CI
      or CVRR at baseline in the CR group. Patients with L-CI or L-CVRR in the CR group
      significantly improved after 12 months. In conclusion, CR may lead various
      hemodynamic parameters obtained using simple non-invasive tests to their
      appropriate levels.

PMID- 29201998
TI  - Treatment and Outcome for Children with Esophageal Atresia from a Gender
      Perspective.
AB  - Background: Besides the incidence of esophageal atresia (EA) being higher in
      males, no other gender-specific differences in EA have been reported. The aim of
      this study was to search for gender-specific differences in EA. Methods: A
      retrospective study was conducted at a tertiary center for pediatric surgery. The
      medical charts of infants born with EA were reviewed. 20 girls were identified,
      and 20 boys were selected as matched controls with respect to concomitant
      malformations. Their treatment and outcome were evaluated. Results:
      Polyhydramnios was more common in pregnancies with boys, 40%, versus girls, 10%,
      with EA (p < 0.01). In total, 36 (90%) children had patent ductus arteriosus,
      without any gender difference (18 and 18, resp., p=1). The distribution of days
      at the different levels of care was not equally distributed between boys and
      girls. Boys with EA had significantly more postoperative days (median 5 days) in
      the ward than girls (median 5 and 2 days, resp., p=0.04). No other gender
      specific differences in surgical treatment, complications, or symptoms at follow
      up were identified. Conclusion: Polyhydramnios appears to be more frequent in
      pregnancies with boys than girls with EA. In this study, boys have longer stays
      than girls at the pediatric surgery ward.

PMID- 29201999
TI  - Clinical impact of prophylactic clip closure of mucosal defects after colorectal
      endoscopic submucosal dissection.
AB  - Background and study aims:  Endoscopic submucosal dissection (ESD) is useful for
      en bloc resection of superficial colorectal neoplasms to ensure accurate
      histologic diagnoses. However, colorectal ESD is associated with a high frequency
      of adverse events (AEs). We aimed to investigate the effectiveness of
      prophylactic clip closure (PCC) of mucosal defects for AEs after colorectal ESD.
      Patients and methods:  This study included 197 patients with 211 lesions who
      underwent colorectal ESD between June 2010 and August 2016. Patients who had
      delayed perforation, delayed bleeding, abdominal pain, or fever were defined as
      AEs after colorectal ESD. Complete PCC was defined as completely sutured mucosal
      defect using endoclips following colorectal ESD, whereas incomplete PCC was
      defined as the mucosal defects that did not enable PCC or were partially sutured.
      Clinical records were retrospectively reviewed and clinical outcomes evaluated.
      Results : AEs occurred in 29 lesions (13.7 %), including 12 with delayed
      bleeding, 12 with fever, 2 with abdominal pain, 2 with fever and abdominal pain,
      and 1 with delayed bleeding and fever. Delayed perforation was not observed in
      any patient. The frequency of AEs was significantly lower in the group with
      complete PCC than in the group with incomplete PCC (7.3 % [9/123] vs. 22.7 %
      [20/88]; P  < 0.001). Multivariate analysis revealed that AEs after colorectal
      ESD were significantly associated with tumor size and submucosal fibrosis.
      Subgroup analysis among the resected specimen size of < 40 mm revealed that there
      was no significant difference in AEs between the 2 groups (5.6 % [6/107] vs. 17.8
      % [8/45]; P  = 0.069). However, the frequency of fever with complete PCC was
      significantly lower than that with incomplete PCC (2.8 % [3/107] vs. 13.3 %
      [6/45]; P  = 0.020). Conclusions : Tumor size and submucosal fibrosis were
      independent risk factors for AEs after colorectal ESD. PCC may be effective in
      minimizing AEs after colorectal ESD, especially the frequency of fever.

PMID- 29202000
TI  - A short telephone-call reminder improves bowel preparation, quality indicators
      and patient satisfaction with first colonoscopy.
AB  - Background and study aims:  Addition of a reminder program to conventional
      indications improves colonoscopy. The aim of this study was to evaluate the
      effectiveness of a short telephone call reminder (STCR) on a patient's first
      colonoscopy. Patients and methods:  One day before colonoscopy, we made a STCR of
      < 10 minutes to 141 randomly selected patients of 258 recruited. The STCRs
      informed patients about the procedure date, indications for taking laxatives, and
      dietetic requirements. Questions were clarified only when patients asked
      directly. We evaluated bowel preparation, quality indicators, and patient
      satisfaction. Data were expressed as mean +/- SD and percentages. Statistical
      differences were evaluated by Student's t and Chi squared tests; alpha = 0.05.
      All authors had access to the study data and reviewed and approved the final
      manuscript. Results:  The STCR group had better bowel preparation which was
      demonstrated by higher completion frequency (97.16 % vs. 82.05 %), in less time
      (4.52 +/- 3.06 vs. 5.38 +/- 3.03 hours) intake of laxative, and higher Boston's
      scale (7.66 +/- 2.42 vs. 5.2 +/- 1.65). Quality indicators of colonoscopy were
      better in patients that received a STCR [cecal intubation rate: 100.00 % vs.
      87.18 %; polyp detection: 42.55 % vs. 9.4 %; and cecal arrival time (min): 12.09
      +/- 3.62 vs. 15.09 +/- 5.02]. STCR patients were more satisfied (97.87 % vs.
      55.56 %) and would repeat colonoscopy (21.99 % vs. 11.11 %). Conclusions:  A
      simple additional step such as a STCR improves quality of bowel preparation,
      quality indicators, and satisfaction of patients undergoing their first
      colonoscopy. Clinical trial registry in Mexico City General Hospital:
      DI/16/107/3/108.

PMID- 29202001
TI  - Validating bowel preparation scales.
AB  - Background and study aim:  Few scales assessing bowel preparation quality have
      been validated, and direct between-scale comparisons remain scarce. The aim of
      the study was to compare inter- and intra-rater reliability, predictive abilities
      for clinical outcomes, and ease of use for each scale. Methods:  Colonoscopy
      video recordings highlighting five colonic segments after washing were viewed
      independently by three physicians, and cleanliness was evaluated using the Boston
      Bowel Preparation Scale (BBPS), the Chicago Bowel Preparation Scale (CBPS), and
      the Harefield Cleansing Scale (HCS) in randomized order. Kappa or intraclass
      correlations quantified intra- and inter-rater reliability. Ease of use was
      evaluated (1 - 10 scale, 1 = easy), as were associations between scores, adenoma
      detection, and adequacy of preparation to exclude lesions >= 5 mm. Results: 
      Among 83 colonoscopy videos, indications included screening or surveillance in
      72.3 %. Mean (+/- SD) scores of the respective three raters were 5.17 +/- 1.57,
      6.49 +/- 1.48, and 5.12 +/- 1.21 for BBPS, and 23.73 +/- 6.01, 28.39 +/- 5.47,
      and 24.75 +/- 5.83 for CBPS, while successful HCS scores (grade A or B) were
      given for 76 %, 89 %, and 63 % of examinations. Intra-rater reliability ranges
      were 0.88 - 1.00, 0.83 - 1.00, and 0.62 - 1.00 for BBPS, CBPS, and HCS,
      respectively. Similarly, inter-rater reliability ranges were 0.50 - 0.79, 0.64 -
      0.83, and 0.28 - 0.52, respectively. Sources of disagreement included varying
      rater strictness, which was possibly most marked for preparations rated as
      intermediate. Overall, associations between preparation scores and adenoma
      detection lacked statistical significance. Conclusion:  The BBPS and CBPS showed
      the best inter- and intra-rater reliability, and the BBPS was considered the
      easiest to use. Further studies are needed to determine an optimal adequacy
      threshold for these scales, with the goal of predicting clinical outcomes and
      determining the appropriate interval to the next colonoscopy.

PMID- 29202002
TI  - A comparison of outcomes between a lumen-apposing metal stent with electrocautery
      enhanced delivery system and a bi-flanged metal stent for drainage of walled-off
      pancreatic necrosis.
AB  - Background and study aims:  Bi-flanged metal stents (BFMS) have shown promise in
      the drainage of walled-off pancreatic necrosis (WON), but their placement
      requires multiple steps and the use of other devices. More recently, a novel
      device consisting of a combined lumen-apposing metal stent (LAMS) and
      electrocautery-enhanced delivery system has been introduced. The aim of this
      study was to compare the placement and outcomes of the two devices. Patients and
      methods:  This was a retrospective review of consecutive patients undergoing
      endoscopic ultrasound-guided placement of BFMS or LAMS for drainage of
      symptomatic WON. Data from procedures between October 2012 and December 2016 were
      taken from a prospectively maintained database. We compared technical and
      clinical success, procedure time, costs, and composite end point of significant
      events (adverse events, stent migration, additional percutaneous drainage)
      between BFMS and LAMS. Results:  72 consecutive patients underwent placement of
      BFMS (40 patients, 44 stents) or LAMS (32 patients, 33 stents). Technical success
      was 91 % for BFMS and 97 % for LAMS. Clinical success was 65 % vs. 78 %,
      respectively. Median in-room procedure time was significantly shorter in the LAMS
      group (45 minutes [range 30 - 80]) than in the BFMS group (62.5 minutes [range 35
      - 135]; P  < 0.001) and fewer direct endoscopic necrosectomies (DEN) were
      performed (median 1 [0 - 2.0] vs. 2 [0 - 3.7], respectively; P  = 0.005). If only
      inpatients were considered (35 BFMS and 19 LAMS), there was no significant
      difference in DEN 2 (range 0 - 11) and 2 (range 0 - 8), respectively. The
      composite end point of 32 % vs. 24 % was not significantly different. Median
      procedural costs for all patients with successful stent placement for WON
      treatment was ?4427 (range 1630 - 12 926) for BFMS vs. ?3500 (range 2509 - 13
      393) for LAMS ( P  = 0.10). Conclusion:  LAMS was superior to BFMS in terms of
      procedure time, with comparable adverse events, success, and costs.

PMID- 29202003
TI  - Implementation of an optical diagnosis strategy saves costs and does not impair
      clinical outcomes of a fecal immunochemical test-based colorectal cancer
      screening program.
AB  - Background and study aims:  In an optical diagnosis strategy, diminutive polyps
      that are endoscopically characterized with high confidence are removed without
      histopathological analysis and distal hyperplastic polyps are left in situ. We
      evaluated the effectiveness and costs of optical diagnosis. Methods:  Using the
      Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model, we simulated
      biennial fecal immunochemical test (FIT) screening in individuals aged 55 - 75
      years. In this program, we compared an optical diagnosis strategy with current
      histopathology assessment of all diminutive polyps. Base-case assumptions
      included 76 % high-confidence predictions and sensitivities of 88 %, 91 %, and 88
      % for endoscopically characterizing adenomas, sessile serrated polyps, and
      hyperplastic polyps, respectively. Outcomes were colorectal cancer burden, number
      of colonoscopies, life-years, and costs. Results:  Both the histopathology
      strategy and the optical diagnosis strategy resulted in 21 life-days gained per
      simulated individual compared with no screening. For optical diagnosis, ?6 per
      individual was saved compared with the current histopathology strategy. These
      cost savings were related to a 31 % reduction in colonoscopies in which
      histopathology was needed for diminutive polyps. Projecting these results onto
      the Netherlands (17 million inhabitants), assuming a fully implemented FIT-based
      screening program, resulted in an annual undiscounted cost saving of ? 1.7 - 2.2
      million for optical diagnosis. Conclusion:  Implementation of optical diagnosis
      in a FIT-based screening program saves costs without decreasing program
      effectiveness when compared with current histopathology analysis of all
      diminutive polyps. Further work is required to evaluate how endoscopists
      participating in a screening program should be trained, audited, and monitored to
      achieve adequate competence in optical diagnosis.

PMID- 29202004
TI  - Should ESGE implement optical diagnosis in Europe?

PMID- 29202005
TI  - Side-by-side partially covered self-expandable metal stent placement for
      malignant hilar biliary obstruction.
AB  - Background and study aims:  This study investigated the feasibility of side-by
      side (SBS) partially covered self-expandable metal stent (PCSEMS) placement for
      unresectable malignant hilar biliary obstruction (MHBO). Patients and methods: 
      We retrospectively analyzed 33 patients from a single center who underwent
      endoscopic biliary drainage for unresectable MHBO from July 2013 to June 2015. In
      all patients with bilateral obstruction during complete bilateral intrahepatic
      cholangiograms, we performed endoscopic SBS placement of a 6-mm diameter PCSEMS
      using an 8-French delivery system. All patients underwent endoscopic
      sphincterotomy. Generally, patients with recurrent biliary obstruction (RBO)
      after stent placement underwent endoscopic reintervention. Our study outcomes
      included the technical and functional success rates, RBO rate, time to RBO
      (TRBO), reintervention rate, and incidence of adverse events. Results:  Seventeen
      patients with unresectable MHBO during complete bilateral intrahepatic
      cholangiograms underwent endoscopic SBS PCSEMS placement (median age, 78 years;
      men, 9). Lesions were Bismuth types II (n = 10), III (n = 1), and IV (n = 6),
      including 10 cholangiocarcinomas, 3 gallbladder cancers, and 4 metastatic
      cancers. In all patients, the PCSEMS was placed across the duodenal papilla. The
      technical and functional success rates were 100 % and 82 %, respectively. The
      median procedure time was 43 minutes (interquartile range [IQR]: 36 - 52
      minutes). Twelve patients had RBO (71 %), including 9 stent occlusions due to
      sludge and 3 stent migrations. The median TRBO was 79 days (IQR: 58 - 156 days)
      during the follow-up period (median 192 days [IQR: 88 - 551 days]). The median
      TRBO of patients with Bismuth type II lesions was significantly longer than that
      of patients with Bismuth types III and IV lesions (87 days [IQR: 70 - 244 days]
      vs. 54 days [IQR: 35 - 100 days]; P  = 0.030). Thirteen patients (76 %) required
      endoscopic reintervention. Endoscopic stent removal was possible in 6 patients
      without tumor ingrowth into the uncovered distal part of the stent. One late
      adverse event (>= 31 days) occurred (cholangitis). Conclusions:  Endoscopic SBS
      placement of a PCSEMS was feasible in patients with unresectable MHBO.
      Additionally, reinterventional stent removal was possible in the absence of tumor
      ingrowth.

PMID- 29202006
TI  - Can we insert a covered stent, partially or not, in case of hilar biliary
      stenosis?

PMID- 29202007
TI  - Epigenetic Advances in Behavioral and Brain Sciences have Relevance for Public
      Policy.
AB  - Nature and nurture work together to drive development, behavior, and health.
      Behavioral epigenetics research has uncovered the underlying mechanisms for how
      this happens. Children's early years in development may offer the greatest
      opportunity for environmental and experiential factors to influence epigenome
      (chemical compounds telling our genes what to do), but evidence suggests it is
      never too late. The policy implications of this research are vast, including
      relevance for child development, health, and disease intervention and prevention.

PMID- 29202008
TI  - Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific
      Inhibition of NF-kappaB.
AB  - Telomerase-specific replication-competent adenoviruses (Ads), i.e., TRADs, which
      possess an E1 gene expression cassette driven by the human telomerase reverse
      transcriptase promoter, are promising agents for cancer treatment. However, even
      though oncolytic Ads, including TRAD, are intratumorally administered, they are
      disseminated from the tumor to systemic circulation, causing concern about
      oncolytic Ad-mediated hepatotoxicity (due mainly to leaky expression of Ad genes
      in liver). We reported that inhibition of nuclear factor-kappaB (NF-kappaB) leads
      to the suppression of replication-incompetent Ad vector-mediated hepatotoxicity
      via reduction of the leaky expression of Ad genes in liver. Here, to develop a
      TRAD with an improved safety profile, we designed a TRAD that carries a liver
      specific promoter-driven dominant-negative IkappaBalpha (DNIkappaBalpha)
      expression cassette (TRAD-DNIkappaBalpha). Compared with a conventional TRAD,
      TRAD-DNIkappaBalpha showed hepatocyte-specific inhibition of NF-kappaB signaling
      and significantly reduced Ad gene expression and replication in the normal human
      hepatocyte cell line. TRAD-induced hepatotoxicity was largely suppressed in mice
      following intravenous administration of TRAD-DNIkappaBalpha. However, the
      replication profiles and oncolytic activities of TRAD-DNIkappaBalpha were
      comparable with those of the conventional TRAD in human non-hepatic tumor cells.
      These results indicate that oncolytic Ads containing the liver-specific
      DNIkappaBalpha expression cassette have improved safety profiles without
      inhibiting oncolytic activities.

PMID- 29202009
TI  - Structural Modeling of Mechanosensitivity in Non-Muscle Cells: Multiscale
      Approach to Understand Cell Sensing.
AB  - The contraction and spreading of nonmuscle cells are important phenomena in a
      number of cellular processes such as differentiation, morphogenesis, and tissue
      growth. Recent experimental work has shown that the topology and the mechanical
      properties of the underlying substrate play a significant role in directing the
      cell's response. In this work, we introduce a multiscale model to understand the
      sensing, activation, and contraction of the actin cytoskeleton of nonmuscle cells
      based on the idea that acto-myosin cross-bridges display a catch-bond response.
      After investigating the respective roles of bond catchiness and acto-myosin
      assembly on the mechano-sensitivity of stress fibers, we present full simulations
      of cells laying on arrays of micropillars. Model predictions show good
      qualitative agreements with experimental observation, suggesting that acto-myosin
      catch bonds are a major mechano-sensing element in nonmuscle cells.

PMID- 29202011
TI  - A Model for Accelerating Patient-to-Bench Research.

PMID- 29202010
TI  - Control over Silica Particle Growth and Particle-Biomolecule Interactions
      Facilitates Silica Encapsulation of Mammalian Cells with Thickness Control.
AB  - Over the last twenty years, many strategies utilizing sol-gel chemistry to
      integrate biological cells into silica-based materials have been reported. One
      such strategy, Sol-Generating Chemical Vapor into Liquid (SG-CViL) deposition,
      shows promise as an efficient encapsulation technique due to the ability to vary
      the silica encapsulation morphology obtained by this process through variation of
      SG-CViL reaction conditions. In this report, we develop SG-CViL as a tunable,
      multi-purpose silica encapsulation strategy by investigating the mechanisms
      governing both silica particle generation and subsequent interaction with
      phospholipid assemblies (liposomes and living cells). Using Dynamic Light
      Scattering (DLS) measurements, linear and exponential silica particle growth
      dynamics were observed which were dependent on deposition buffer ion constituents
      and ion concentration. Silica particle growth followed a cluster-cluster growth
      mechanism at acidic pH, and a monomer-cluster growth mechanism at neutral to
      basic pH. Increasing silica sol aging temperature resulted in higher rates of
      particle growth and larger particles. DLS measurements employing PEG coated
      liposomes and cationic liposomes, serving as model phospholipid assemblies,
      revealed electrostatic interactions promote more stable liposome-silica
      interactions than hydrogen bonding and facilitate silica coating on suspension
      cells. However, continued silica reactivity leads to aggregation of silica coated
      suspensions cells, revealing the need for cell isolation to tune deposited silica
      thickness. Utilizing these mechanistic study insights, silica was deposited onto
      adherent HeLa cells under biocompatible conditions with micron scale control over
      silica thickness, minimal cell manipulation steps, and retained cell viability
      over several days.

PMID- 29202012
TI  - A Conversation with Yuegang Zhang.

PMID- 29202013
TI  - A Home Away from Home.

PMID- 29202014
TI  - When Electrochemistry Met Methane: Rapid Catalyst Oxidation Fuels Hydrocarbon
      Functionalization.

PMID- 29202015
TI  - Immunity to alpha-Gal: Toward a Single-Antigen Pan-Vaccine To Control Major
      Infectious Diseases.

PMID- 29202016
TI  - Inhibition of NGLY1 Inactivates the Transcription Factor Nrf1 and Potentiates
      Proteasome Inhibitor Cytotoxicity.
AB  - Proteasome inhibitors are used to treat blood cancers such as multiple myeloma
      (MM) and mantle cell lymphoma. The efficacy of these drugs is frequently
      undermined by acquired resistance. One mechanism of proteasome inhibitor
      resistance may involve the transcription factor Nuclear Factor, Erythroid 2 Like
      1 (NFE2L1, also referred to as Nrf1), which responds to proteasome insufficiency
      or pharmacological inhibition by upregulating proteasome subunit gene expression.
      This "bounce-back" response is achieved through a unique mechanism. Nrf1 is
      constitutively translocated into the ER lumen, N-glycosylated, and then targeted
      for proteasomal degradation via the ER-associated degradation (ERAD) pathway.
      Proteasome inhibition leads to accumulation of cytosolic Nrf1, which is then
      processed to form the active transcription factor. Here we show that the
      cytosolic enzyme N-glycanase 1 (NGLY1, the human PNGase) is essential for Nrf1
      activation in response to proteasome inhibition. Chemical or genetic disruption
      of NGLY1 activity results in the accumulation of misprocessed Nrf1 that is
      largely excluded from the nucleus. Under these conditions, Nrf1 is inactive in
      regulating proteasome subunit gene expression in response to proteasome
      inhibition. Through a small molecule screen, we identified a cell-active NGLY1
      inhibitor that disrupts the processing and function of Nrf1. The compound
      potentiates the cytotoxicity of carfilzomib, a clinically used proteasome
      inhibitor, against MM and T cell-derived acute lymphoblastic leukemia (T-ALL)
      cell lines. Thus, NGLY1 inhibition prevents Nrf1 activation and represents a new
      therapeutic approach for cancers that depend on proteasome homeostasis.

PMID- 29202018
TI  - Precise Probing of Residue Roles by Post-Translational beta,gamma-C,N Aza-Michael
      Mutagenesis in Enzyme Active Sites.
AB  - Biomimicry valuably allows the understanding of the essential chemical components
      required to recapitulate biological function, yet direct strategies for
      evaluating the roles of amino acids in proteins can be limited by access to
      suitable, subtly-altered unnatural variants. Here we describe a strategy for
      dissecting the role of histidine residues in enzyme active sites using
      unprecedented, chemical, post-translational side-chain-beta,gamma C-N bond
      formation. Installation of dehydroalanine (as a "tag") allowed the testing of
      nitrogen conjugate nucleophiles in "aza-Michael"-1,4-additions (to "modify").
      This allowed the creation of a regioisomer of His (iso-His, Hisiso) linked
      instead through its pros-Npi atom rather than naturally linked via C4, as well as
      an aza-altered variant aza-Hisiso. The site-selective generation of these
      unnatural amino acids was successfully applied to probe the contributing roles
      (e.g., size, H-bonding) of His residues toward activity in the model enzymes
      subtilisin protease from Bacillus lentus and Mycobacterium tuberculosis
      pantothenate synthetase.

PMID- 29202019
TI  - Catalytic Methane Monofunctionalization by an Electrogenerated High-Valent Pd
      Intermediate.
AB  - Electrophilic high-valent metal ions are potent intermediates for the catalytic
      functionalization of methane, but in many cases, their high redox potentials make
      these intermediates difficult or impossible to access using mild stoichiometric
      oxidants derived from O2. Herein, we establish electrochemical oxidation as a
      versatile new strategy for accessing high-valent methane monofunctionalization
      catalysts. We provide evidence for the electrochemical oxidation of simple PdSO4
      in concentrated sulfuric acid electrolytes to generate a putative Pd2III,III
      species in an all-oxidic ligand field. This electrogenerated high-valent Pd
      complex rapidly activates methane with a low barrier of 25.9 (+/-2.6) kcal/mol,
      generating methanol precursors methyl bisulfate (CH3OSO3H) and methanesulfonic
      acid (CH3SO3H) via concurrent faradaic and nonfaradaic reaction pathways. This
      work enables new electrochemical approaches for promoting rapid methane
      monofunctionalization.

PMID- 29202017
TI  - Molecular Motor Dnm1 Synergistically Induces Membrane Curvature To Facilitate
      Mitochondrial Fission.
AB  - Dnm1 and Fis1 are prototypical proteins that regulate yeast mitochondrial
      morphology by controlling fission, the dysregulation of which can result in
      developmental disorders and neurodegenerative diseases in humans. Loss of Dnm1
      blocks the formation of fission complexes and leads to elongated mitochondria in
      the form of interconnected networks, while overproduction of Dnm1 results in
      excessive mitochondrial fragmentation. In the current model, Dnm1 is essentially
      a GTP hydrolysis-driven molecular motor that self-assembles into ring-like
      oligomeric structures that encircle and pinch the outer mitochondrial membrane at
      sites of fission. In this work, we use machine learning and synchrotron small
      angle X-ray scattering (SAXS) to investigate whether the motor Dnm1 can
      synergistically facilitate mitochondrial fission by membrane remodeling. A
      support vector machine (SVM)-based classifier trained to detect sequences with
      membrane-restructuring activity identifies a helical Dnm1 domain capable of
      generating negative Gaussian curvature (NGC), the type of saddle-shaped local
      surface curvature found on scission necks during fission events. Furthermore,
      this domain is highly conserved in Dnm1 homologues with fission activity.
      Synchrotron SAXS measurements reveal that Dnm1 restructures membranes into phases
      rich in NGC, and is capable of inducing a fission neck with a diameter of 12.6
      nm. Through in silico mutational analysis, we find that the helical Dnm1 domain
      is locally optimized for membrane curvature generation, and phylogenetic analysis
      suggests that dynamin superfamily proteins that are close relatives of human
      dynamin Dyn1 have evolved the capacity to restructure membranes via the induction
      of curvature mitochondrial fission. In addition, we observe that Fis1, an adaptor
      protein, is able to inhibit the pro-fission membrane activity of Dnm1, which
      points to the antagonistic roles of the two proteins in the regulation of
      mitochondrial fission.

PMID- 29202020
TI  - Computational Model and Dynamics of Monomeric Full-Length APOBEC3G.
AB  - APOBEC3G (A3G) is a restriction factor that provides innate immunity against HIV
      1 in the absence of viral infectivity factor (Vif) protein. However, structural
      information about A3G, which can aid in unraveling the mechanisms that govern its
      interactions and define its antiviral activity, remains unknown. Here, we built a
      computer model of a full-length A3G using docking approaches and molecular
      dynamics simulations, based on the available X-ray and NMR structural data for
      the two protein domains. The model revealed a large-scale dynamics of the A3G
      monomer, as the two A3G domains can assume compact forms or extended dumbbell
      type forms with domains visibly separated from each other. To validate the A3G
      model, we performed time-lapse high-speed atomic force microscopy (HS-AFM)
      experiments enabling us to get images of a fully hydrated A3G and to directly
      visualize its dynamics. HS-AFM confirmed that A3G exists in two forms, a globular
      form (~84% of the time) and a dumbbell form (~16% of the time), and can
      dynamically switch from one form to the other. The obtained HS-AFM results are in
      line with the computer modeling, which demonstrates a similar distribution
      between two forms. Furthermore, our simulations capture the complete process of
      A3G switching from the DNA-bound state to the closed state. The revealed dynamic
      nature of monomeric A3G could aid in target recognition including scanning for
      cytosine locations along the DNA strand and in interactions with viral RNA during
      packaging into HIV-1 particles.

PMID- 29202021
TI  - Bimetallic Effect of Single Nanocatalysts Visualized by Super-Resolution
      Catalysis Imaging.
AB  - Compared with their monometallic counterparts, bimetallic nanoparticles often
      show enhanced catalytic activity associated with the bimetallic interface. Direct
      quantitation of catalytic activity at the bimetallic interface is important for
      understanding the enhancement mechanism, but challenging experimentally. Here
      using single-molecule super-resolution catalysis imaging in correlation with
      electron microscopy, we report the first quantitative visualization of enhanced
      bimetallic activity within single bimetallic nanoparticles. We focus on
      heteronuclear bimetallic PdAu nanoparticles that present a well-defined Pd-Au
      bimetallic interface in catalyzing a photodriven fluorogenic disproportionation
      reaction. Our approach also enables a direct comparison between the bimetallic
      and monometallic regions within the same nanoparticle. Theoretical calculations
      further provide insights into the electronic nature of N-O bond activation of the
      reactant (resazurin) adsorbed on bimetallic sites. Subparticle activity
      correlation between bimetallic enhancement and monometallic activity suggests
      that the favorable locations to construct bimetallic sites are those monometallic
      sites with higher activity, leading to a strategy for making effective bimetallic
      nanocatalysts. The results highlight the power of super-resolution catalysis
      imaging in gaining insights that could help improve nanocatalysts.

PMID- 29202022
TI  - Reversible Self-Assembled Monolayers (rSAMs): Adaptable Surfaces for Enhanced
      Multivalent Interactions and Ultrasensitive Virus Detection.
AB  - We report on the design of pH-switchable monolayers allowing a reversible and
      ordered introduction of affinity reagents on sensor surfaces. The principal layer
      building blocks consist of alpha-(4-amidinophenoxy)alkanes decorated at the omega
      position with affinity ligands. These spontaneously self-assemble on top of
      carboxylic acid terminated SAMs to form reversible homo or mixed monolayers
      (rSAMs) that are tunable with respect to the nature of the head group, layer
      order and stability while featuring pH responsiveness and the dynamic nature of
      noncovalent build assemblies. We show that this results in a range of unique
      biosensor features. As a first example a sialic acid rSAM featuring strong lectin
      affinity is here used to sense hemagglutinin and influenza virus (H5N1) at the pM
      and fM level by in situ ellipsometry in a fully reversible fashion. We believe
      that the rSAM concept will find widespread use in surface chemistry and overall
      for boosting sensitivity in affinity biosensors.

PMID- 29202023
TI  - Combating Drug-Resistant Mutants of Anaplastic Lymphoma Kinase with Potent and
      Selective Type-I1/2 Inhibitors by Stabilizing Unique DFG-Shifted Loop
      Conformation.
AB  - Targeted inhibition of anaplastic lymphoma kinase (ALK) dramatically improved
      therapeutic outcomes in the treatment of ALK-positive cancers, but unfortunately
      patients invariably progressed due to acquired resistance mutations in ALK.
      Currently available drugs are all type-I inhibitors bound to the ATP-binding
      pocket and are most likely to be resistant in patients harboring genetic
      mutations surrounding the ATP pocket. To overcome drug resistance, we rationally
      designed a novel kind of "bridge" inhibitor, which specially bind into an
      extended hydrophobic back pocket adjacent to the ATP-binding site of ALK. The
      novel type-I1/2 inhibitors display excellent antiproliferation activity against
      ALK-positive cancer cells and appear superior to two clinically used drugs,
      crizotinib and ceritinib. Structural and molecular modeling analyses indicate
      that the inhibitor induces dramatic conformational transition and stabilizes
      unique DFG-shifted loop conformation, enabling persistent sensitivity to
      different genetic mutations in ALK. These data highlight a rationale for further
      development of next-generation ALK inhibitors to combat drug resistance.

PMID- 29202024
TI  - Highly Active Fe Sites in Ultrathin Pyrrhotite Fe7S8 Nanosheets Realizing
      Efficient Electrocatalytic Oxygen Evolution.
AB  - Identification of active sites in an electrocatalyst is essential for
      understanding of the mechanism of electrocatalytic water splitting. To be one of
      the most active oxygen evolution reaction catalysts in alkaline media, Ni-Fe
      based compounds have attracted tremendous attention, while the role of Ni and Fe
      sites played has still come under debate. Herein, by taking the pyrrhotite Fe7S8
      nanosheets with mixed-valence states and metallic conductivity for examples, we
      illustrate that Fe could be a highly active site for electrocatalytic oxygen
      evolution. It is shown that the delocalized electrons in the ultrathin Fe7S8
      nanosheets could facilitate electron transfer processes of the system, where d
      orbitals of FeII and FeIII would be overlapped with each other during the
      catalytic reactions, rendering the ultrathin Fe7S8 nanosheets to be the most
      efficient Fe-based electrocatalyst for water oxidation. As expected, the
      ultrathin Fe7S8 nanosheets exhibit promising electrocatalytic oxygen evolution
      activities, with a low overpotential of 0.27 V and a large current density of 300
      mA cm-2 at 0.5 V. This work provides solid evidence that Fe could be an efficient
      active site for electrocatalytic water splitting.

PMID- 29202025
TI  - Ultrafast dynamics of vibrational symmetry breaking in a charge-ordered
      nickelate.
AB  - The ability to probe symmetry-breaking transitions on their natural time scales
      is one of the key challenges in nonequilibrium physics. Stripe ordering
      represents an intriguing type of broken symmetry, where complex interactions
      result in atomic-scale lines of charge and spin density. Although phonon
      anomalies and periodic distortions attest the importance of electron-phonon
      coupling in the formation of stripe phases, a direct time-domain view of
      vibrational symmetry breaking is lacking. We report experiments that track the
      transient multi-terahertz response of the model stripe compound La1.75Sr0.25NiO4,
      yielding novel insight into its electronic and structural dynamics following an
      ultrafast optical quench. We find that although electronic carriers are
      immediately delocalized, the crystal symmetry remains initially frozen-as
      witnessed by time-delayed suppression of zone-folded Ni-O bending modes acting as
      a fingerprint of lattice symmetry. Longitudinal and transverse vibrations react
      with different speeds, indicating a strong directionality and an important role
      of polar interactions. The hidden complexity of electronic and structural
      coupling during stripe melting and formation, captured here within a single
      terahertz spectrum, opens new paths to understanding symmetry-breaking dynamics
      in solids.

PMID- 29202026
TI  - Spatial and temporal seismic velocity changes on Kyushu Island during the 2016
      Kumamoto earthquake.
AB  - Monitoring of earthquake faults and volcanoes contributes to our understanding of
      their dynamic mechanisms and to our ability to predict future earthquakes and
      volcanic activity. We report here on spatial and temporal variations of seismic
      velocity around the seismogenic fault of the 2016 Kumamoto earthquake [moment
      magnitude (Mw) 7.0] based on ambient seismic noise. Seismic velocity near the
      rupture faults and Aso volcano decreased during the earthquake. The velocity
      reduction near the faults may have been due to formation damage, a change in
      stress state, and an increase in pore pressure. Further, we mapped the post
      earthquake fault-healing process. The largest seismic velocity reduction observed
      at Aso volcano during the earthquake was likely caused by pressurized volcanic
      fluids, and the large increase in seismic velocity at the volcano's magma body
      observed ~3 months after the earthquake may have been a response to
      depressurization caused by the eruption. This study demonstrates the usefulness
      of continuous monitoring of faults and volcanoes.

PMID- 29202027
TI  - Seismic potential of weak, near-surface faults revealed at plate tectonic slip
      rates.
AB  - The near-surface areas of major faults commonly contain weak, phyllosilicate
      minerals, which, based on laboratory friction measurements, are assumed to creep
      stably. However, it is now known that shallow faults can experience tens of
      meters of earthquake slip and also host slow and transient slip events.
      Laboratory experiments are generally performed at least two orders of magnitude
      faster than plate tectonic speeds, which are the natural driving conditions for
      major faults; the absence of experimental data for natural driving rates
      represents a critical knowledge gap. We use laboratory friction experiments on
      natural fault zone samples at driving rates of centimeters per year to
      demonstrate that there is abundant evidence of unstable slip behavior that was
      not previously predicted. Specifically, weak clay-rich fault samples generate
      slow slip events (SSEs) and have frictional properties favorable for earthquake
      rupture. Our work explains growing field observations of shallow SSE and surface
      breaking earthquake slip, and predicts that such phenomena should be more widely
      expected.

PMID- 29202028
TI  - Provably secure and high-rate quantum key distribution with time-bin qudits.
AB  - The security of conventional cryptography systems is threatened in the
      forthcoming era of quantum computers. Quantum key distribution (QKD) features
      fundamentally proven security and offers a promising option for quantum-proof
      cryptography solution. Although prototype QKD systems over optical fiber have
      been demonstrated over the years, the key generation rates remain several orders
      of magnitude lower than current classical communication systems. In an effort
      toward a commercially viable QKD system with improved key generation rates, we
      developed a discrete-variable QKD system based on time-bin quantum photonic
      states that can generate provably secure cryptographic keys at megabit-per-second
      rates over metropolitan distances. We use high-dimensional quantum states that
      transmit more than one secret bit per received photon, alleviating detector
      saturation effects in the superconducting nanowire single-photon detectors used
      in our system that feature very high detection efficiency (of more than 70%) and
      low timing jitter (of less than 40 ps). Our system is constructed using
      commercial off-the-shelf components, and the adopted protocol can be readily
      extended to free-space quantum channels. The security analysis adopted to distill
      the keys ensures that the demonstrated protocol is robust against coherent
      attacks, finite-size effects, and a broad class of experimental imperfections
      identified in our system.

PMID- 29202029
TI  - Discriminating between natural versus induced seismicity from long-term
      deformation history of intraplate faults.
AB  - To assess whether recent seismicity is induced by human activity or is of natural
      origin, we analyze fault displacements on high-resolution seismic reflection
      profiles for two regions in the central United States (CUS): the Fort Worth Basin
      (FWB) of Texas and the northern Mississippi embayment (NME). Since 2009,
      earthquake activity in the CUS has increased markedly, and numerous publications
      suggest that this increase is primarily due to induced earthquakes caused by deep
      well injection of wastewater, both flowback water from hydrofracturing operations
      and produced water accompanying hydrocarbon production. Alternatively, some argue
      that these earthquakes are natural and that the seismicity increase is a normal
      variation that occurs over millions of years. Our analysis shows that within the
      NME, faults deform both Quaternary alluvium and underlying sediments dating from
      Paleozoic through Tertiary, with displacement increasing with geologic unit age,
      documenting a long history of natural activity. In the FWB, a region of ongoing
      wastewater injection, basement faults show deformation of the Proterozoic and
      Paleozoic units, but little or no deformation of younger strata. Specifically,
      vertical displacements in the post-Pennsylvanian formations, if any, are below
      the resolution (~15 m) of the seismic data, far less than expected had these
      faults accumulated deformation over millions of years. Our results support the
      assertion that recent FWB earthquakes are of induced origin; this conclusion is
      entirely independent of analyses correlating seismicity and wastewater injection
      practices. To our knowledge, this is the first study to discriminate natural and
      induced seismicity using classical structural geology analysis techniques.

PMID- 29202030
TI  - The prevalence of kilometer-scale heterogeneity in the source region of MORB
      upper mantle.
AB  - The source regions of mid-ocean ridge basalts (MORB) are heterogeneous,
      consisting of chemically and lithologically distinct domains of variable size.
      Partial melting of such heterogeneous mantle sources gives rise to diverse
      isotopic compositions of MORB and abyssal peridotites. Variations in radiogenic
      isotope ratios in MORB are attributed to mixing of melts derived from enriched
      and depleted mantle components. However, melt mixing alone cannot fully account
      for the difference between the average 143Nd/144Nd in abyssal peridotites and
      their spatially associated MORB. We show that the more depleted Nd isotope
      composition in abyssal peridotites is a natural consequence of melt migration
      induced mixing or smearing in the melting column. Sub-kilometer scale enriched
      mantle components or heterogeneities are significantly damped or homogenized in
      both the residue and erupted melt during their transit through the melting
      region. Heterogeneities with larger size and higher incompatible trace element
      abundance are more resistive to the mixing processes. The size-sensitive mixing
      depends on a parameter called the enrichment strength, which is the product of
      the heterogeneity size and the ratio between incompatible trace element abundance
      in the enriched and depleted mantle sources. Observed Nd-Hf isotope variations in
      MORB and abyssal peridotites can be reproduced if the enrichment strength is 20
      to 60 km. These heterogeneities could be on the kilometer scale and have similar
      isotope ratios to but less incompatible trace element abundances than recycled
      oceanic crust.

PMID- 29202031
TI  - Stitching h-BN by atomic layer deposition of LiF as a stable interface for
      lithium metal anode.
AB  - Defects are important features in two-dimensional (2D) materials that have a
      strong influence on their chemical and physical properties. Through the enhanced
      chemical reactivity at defect sites (point defects, line defects, etc.), one can
      selectively functionalize 2D materials via chemical reactions and thereby tune
      their physical properties. We demonstrate the selective atomic layer deposition
      of LiF on defect sites of h-BN prepared by chemical vapor deposition. The LiF
      deposits primarily on the line and point defects of h-BN, thereby creating seams
      that hold the h-BN crystallites together. The chemically and mechanically stable
      hybrid LiF/h-BN film successfully suppresses lithium dendrite formation during
      both the initial electrochemical deposition onto a copper foil and the subsequent
      cycling. The protected lithium electrodes exhibit good cycling behavior with more
      than 300 cycles at relatively high coulombic efficiency (>95%) in an additive
      free carbonate electrolyte.

PMID- 29202032
TI  - Biomass recycling and Earth's early phosphorus cycle.
AB  - Phosphorus sets the pace of marine biological productivity on geological time
      scales. Recent estimates of Precambrian phosphorus levels suggest a severe
      deficit of this macronutrient, with the depletion attributed to scavenging by
      iron minerals. We propose that the size of the marine phosphorus reservoir was
      instead constrained by muted liberation of phosphorus during the remineralization
      of biomass. In the modern ocean, most biomass-bound phosphorus gets aerobically
      recycled; but a dearth of oxidizing power in Earth's early oceans would have
      limited the stoichiometric capacity for remineralization, particularly during the
      Archean. The resulting low phosphorus concentrations would have substantially
      hampered primary productivity, contributing to the delayed rise of atmospheric
      oxygen.

PMID- 29202033
TI  - Synthetic "smart gel" provides glucose-responsive insulin delivery in diabetic
      mice.
AB  - Although previous studies have attempted to create "electronics-free" insulin
      delivery systems using glucose oxidase and sugar-binding lectins as a glucose
      sensing mechanism, no successful clinical translation has hitherto been made.
      These protein-based materials are intolerant of long-term use and storage because
      of their denaturing and/or cytotoxic properties. We provide a solution by
      designing a protein-free and totally synthetic material-based approach.
      Capitalizing on the sugar-responsive properties of boronic acid, we have
      established a synthetic polymer gel-based insulin delivery device confined within
      a single catheter, which exhibits an artificial pancreas-like function in vivo.
      Subcutaneous implantation of the device in healthy and diabetic mice establishes
      a closed-loop system composed of "continuous glucose sensing" and "skin layer"
      regulated insulin release. As a result, glucose metabolism was controlled in
      response to interstitial glucose fluctuation under both insulin-deficient and
      insulin-resistant conditions with at least 3-week durability. Our "smart gel"
      technology could offer a user-friendly and remarkably economic (disposable)
      alternative to the current state of the art, thereby facilitating availability of
      effective insulin treatment not only to diabetic patients in developing countries
      but also to those patients who otherwise may not be strongly motivated, such as
      the elderly, infants, and patients in need of nursing care.

PMID- 29202034
TI  - Race-Ethnicity and Prescription Drug Misuse: Does Self-esteem Matter?
AB  - The research here investigates race-ethnicity and self-esteem in the misuse of
      prescription drugs. While there has been much research into the demographic
      factors that predict prescription drug misuse (PDM), we lack a full accounting of
      psychosocial factors of possible importance in influencing patterns of race
      ethnicity and PDM. One possible influence is self-esteem. We use data from the
      National Longitudinal Survey on Adolescent Health to investigate race-ethnicity,
      PDM and self-esteem. Findings indicate first that race-ethnicity is significant
      is PDM. Secondly, results indicate that self-esteem is important in understanding
      patterns of prescription drug misuse among young adults, but only among whites.

PMID- 29202035
TI  - Through the Eustachian Tube and Beyond: A New Miniature Robotic Endoscope to See
      Into The Middle Ear.
AB  - This paper presents a novel miniature robotic endoscope that is small enough to
      pass through the Eustachian tube and provide visualization of the middle ear
      (ME). The device features a miniature bending tip previously conceived of as a
      small-scale robotic wrist that has been adapted to carry and aim a small chip-tip
      camera and fiber optic light sources. The motivation for trans-Eustachian tube ME
      inspection is to provide a natural-orifice-based route to the ME that does not
      require cutting or lifting the eardrum, as is currently required. In this paper,
      we first perform an analysis of the ME anatomy and use a computational design
      optimization platform to derive the kinematic requirements for endoscopic
      inspection of the ME through the Eustachian tube. Based on these requirements, we
      fabricate the proposed device and use it to demonstrate the feasibility of ME
      inspection in an anthropomorphic model, i.e. a 3D-printed ME phantom generated
      from patient image data. We show that our prototype provides > 74% visibility
      coverage of the sinus tympani, a region of the ME crucial for diagnosis, compared
      to an average of only 6.9% using a straight, non-articulated endoscope through
      the Eustachian Tube.

PMID- 29202037
TI  - Comparative Profiling of Ubiquitin Proteasome System Interplay with Influenza A
      Virus PB2 Polymerase Protein Recapitulating Virus Evolution in Humans.
AB  - The optimized exploitation of cell resources is one cornerstone of a successful
      infection. Differential mapping of host-pathogen protein-protein interactions
      (PPIs) on the basis of comparative interactomics of multiple strains is an
      effective strategy to highlight correlations between host proteome hijacking and
      biological or pathogenic traits. Here, we developed an interactomic pipeline to
      deliver high-confidence comparative maps of PPIs between a given pathogen and the
      human ubiquitin proteasome system (UPS). This subarray of the human proteome
      represents a range of essential cellular functions and promiscuous targets for
      many viruses. The screening pipeline was applied to the influenza A virus (IAV)
      PB2 polymerase proteins of five strains representing different levels of
      virulence in humans. An extensive PB2-UPS interplay has been detected that
      recapitulates the evolution of IAVs in humans. Functional validation with several
      IAV strains, including the seasonal H1N1pdm09 and H3N2 viruses, confirmed the
      biological relevance of most identified UPS factors and revealed strain
      independent and strain-specific effects of UPS factor invalidation on IAV
      infection. This strategy is applicable to proteins from any other virus or
      pathogen, providing a valuable resource with which to explore the UPS-pathogen
      interplay and its relationship with pathogenicity. IMPORTANCE Influenza A viruses
      (IAVs) are responsible for mild-to-severe seasonal respiratory illness of public
      health concern worldwide, and the risk of avian strain outbreaks in humans is a
      constant threat. Elucidating the requisites of IAV adaptation to humans is thus
      of prime importance. In this study, we explored how PB2 replication proteins of
      IAV strains with different levels of virulence in humans hijack a major protein
      modification pathway of the human host cell, the ubiquitin proteasome system
      (UPS). We found that the PB2 protein engages in an extended interplay with the
      UPS that evolved along with the virus's adaptation to humans. This suggests that
      UPS hijacking underlies the efficient infection of humans and can be used as an
      indicator for evaluation of the potential of avian IAVs to infect humans. Several
      UPS factors were found to be necessary for infection with circulating IAV
      strains, pointing to potential targets for therapeutic approaches.

PMID- 29202036
TI  - Free-radicals and advanced chemistries involved in cell membrane organization
      influence oxygen diffusion and pathology treatment.
AB  - A breakthrough has been discovered in pathology chemistry related to increasing
      molecular structure that can interfere with oxygen diffusion through cell
      membranes. Free radicals can crosslink unsaturated low-viscosity fatty acid oils
      by chain-growth polymerization into more viscous liquids and even solids. Free
      radicals are released by mitochondria in response to intermittent hypoxia that
      can increase membrane molecular organization to reduce fluidity and oxygen
      diffusion in a possible continuing vicious cycle toward pathological disease.
      Alternate computational chemistry demonstrates molecular bond dynamics in free
      energy for cell membrane physiologic movements. Paired electrons in oxygen and
      nitrogen atoms require that oxygen bonds rotate and nitrogen bonds invert to seek
      polar nano-environments and hide from nonpolar nano-environments thus creating
      fluctuating instability at a nonpolar membrane and polar biologic fluid
      interface. Subsequent mechanomolecular movements provide free energy to increase
      diffusion by membrane transport of molecules and oxygen into the cell, cell
      membrane signaling/recognition/defense in addition to protein movements for
      enzyme mixing. In other chemistry calcium bonds to membrane phosphates primarily
      on the outer plasma cell membrane surface to influence the membrane firing
      threshold for excitability and better seal out water permeation. Because calcium
      is an excellent metal conductor and membrane phosphate headgroups form a
      semiconductor at the biologic fluid interface, excess electrons released by
      mitochondria may have more broad dissipation potential by safe conduction through
      calcium atomic-sized circuits on the outer membrane surface. Regarding medical
      conditions, free radicals are known to produce pathology especially in age
      related disease in addition to aging. Because cancer cell membranes develop
      extreme polymorphism that has been extensively followed in research, accentuated
      easily-visualized free-radical models are developed. In terms of treatment, use
      of vitamin nutrient supplements purported to be antioxidants that remove free
      radicals has not proved worthwhile in clinical trials presumably due to errors
      with early antioxidant measurements based on inaccurate colorimetry tests.
      However, newer covalent-bond shrinkage tests now provide accurate measurements
      for free-radical inhibitor hydroquinone and other molecules toward drug therapy.

PMID- 29202038
TI  - A Novel Biomimetic Nanosponge Protects the Retina from the Enterococcus faecalis
      Cytolysin.
AB  - Intraocular infections are a potentially blinding complication of common ocular
      surgeries and traumatic eye injuries. Bacterial toxins synthesized in the eye can
      damage intraocular tissue, often resulting in poor visual outcomes. Enteroccocus
      faecalis causes blinding infections and is responsible for 8 to 17% of
      postoperative endophthalmitis cases. These infections are increasingly difficult
      to treat due to the emergence of multidrug-resistant strains. Virulent E.
      faecalis isolates secrete a pore-forming bicomponent cytolysin that contributes
      to retinal tissue damage during endophthalmitis. We hypothesized that a
      biomimetic nanosponge, which mimics erythrocytes, might adsorb subunits of the
      cytolysin and reduce retinal damage, protecting vision. To test the efficacy of
      nanosponges in neutralizing the cytolysin in vitro, hemoglobin release assays
      were performed on culture supernatants from cytolysin-producing E. faecalis with
      and without preincubation with nanosponges. Treatment with nanosponges for 30 min
      reduced hemolytic activity by ~70%. To determine whether nanosponges could
      neutralize the cytolysin in vivo, electroretinography was performed on mice 24 h
      after intravitreal injection with cytolysin-containing supernatants treated with
      nanosponges. Pretreatment of cytolysin-containing supernatants with nanosponges
      increased the A-wave retention from 12.2% to 65.5% and increased the B-wave
      retention from 21.0% to 77.0%. Histology revealed that in nanosponge-treated
      eyes, retinas remained intact and attached, with little to no damage. Rabbit
      nanosponges were also nontoxic and noninflammatory when injected into mouse eyes.
      In an experimental murine model of E. faecalis endophthalmitis, injection of
      nanosponges into the vitreous 6 h after infection with a wild-type cytolysin
      producing strain increased A-wave retention from 5.9% to 31% and increased B-wave
      retention from 12.6% to 27.8%. Together, these results demonstrated that
      biomimetic nanosponges neutralized cytolysin activity and protected the retinas
      from damage. These results suggest that this novel strategy might also protect
      eyes from the activities of pore-forming toxins of other virulent ocular
      bacterial pathogens. IMPORTANCE Endophthalmitis is a serious, potentially
      blinding infection that can result in vision loss, leaving a patient with only
      the ability to count fingers, or it may require enucleation of the globe. The
      incidence of postoperative endophthalmitis has markedly increased over the past 2
      decades, paralleling the rise in ocular surgeries and intravitreal therapies. E.
      faecalis is a leading cause of infection following ocular procedures, and such
      infections are increasingly difficult to treat due to multidrug resistance.
      Cytolysin is the primary virulence factor responsible for retinal tissue damage
      in E. faecalis eye infections. Treatment of these infections with antibiotics
      alone does not impede ocular damage and loss of visual function. Pore-forming
      toxins (PFTs) have been established as major virulence factors in endophthalmitis
      caused by several bacterial species. These facts establish a critical need for a
      novel therapy to neutralize bacterial PFTs such as cytolysin. Here, we
      demonstrate that biomimetic nanosponges neutralize cytolysin, protect the retina,
      preserve vision, and may provide an adjunct detoxification therapy for bacterial
      infections.

PMID- 29202039
TI  - Genomic, Network, and Phylogenetic Analysis of the Oomycete Effector Arsenal.
AB  - The oomycetes are a class of microscopic, filamentous eukaryotes within the
      stramenopiles-alveolate-Rhizaria (SAR) supergroup and include ecologically
      significant animal and plant pathogens. Oomycetes secrete large arsenals of
      effector proteins that degrade host cell components, manipulate host immune
      responses, and induce necrosis, enabling parasitic colonization. This study
      investigated the expansion and evolution of effectors in 37 oomycete species in 4
      oomycete orders, including Albuginales, Peronosporales, Pythiales, and
      Saprolegniales species. Our results highlight the large expansions of effector
      protein families, including glycoside hydrolases, pectinases, and necrosis
      inducing proteins, in Phytophthora species. Species-specific expansions,
      including expansions of chitinases in Aphanomyces astaci and Pythium oligandrum,
      were detected. Novel effectors which may be involved in suppressing animal immune
      responses in Ap. astaci and Py. insidiosum were also identified. Type 2 necrosis
      inducing proteins with an unusual phylogenetic history were also located in a
      number of oomycete species. We also investigated the "RxLR" effector complement
      of all 37 species and, as expected, observed large expansions in Phytophthora
      species numbers. Our results provide in-depth sequence information on all
      putative RxLR effectors from all 37 species. This work represents an up-to-date
      in silico catalogue of the effector arsenal of the oomycetes based on the 37
      genomes currently available. IMPORTANCE The oomycetes are a class of microscopic,
      filamentous eukaryotes and include ecologically significant animal and plant
      pathogens. Oomycetes secrete large arsenals of effector proteins that degrade
      host cell components, manipulate host immune responses, and induce necrosis,
      enabling parasitic colonization. In this study, we catalogued the number and
      evolution of effectors in 37 oomycete species whose genomes have been completely
      sequenced. Large expansions of effector protein families in Phytophthora species,
      including glycoside hydrolases, pectinases, and necrosis-inducing proteins, were
      observed. Species-specific expansions were detected, including chitinases in
      Aphanomyces astaci and Pythium oligandrum. Novel effectors which may be involved
      in suppressing animal immune responses were identified in Ap. astaci and Py.
      oligandrum. Type 2 necrosis-inducing proteins with an unusual phylogenetic
      history were also located. This work represents an up-to-date in silico catalogue
      of the effector arsenal of the oomycetes based on the 37 genomes currently
      available.

PMID- 29202040
TI  - A Simple and Universal System for Gene Manipulation in Aspergillus fumigatus: In
      Vitro-Assembled Cas9-Guide RNA Ribonucleoproteins Coupled with Microhomology
      Repair Templates.
AB  - CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 is a novel
      genome-editing system that has been successfully established in Aspergillus
      fumigatus. However, the current state of the technology relies heavily on DNA
      based expression cassettes for delivering Cas9 and the guide RNA (gRNA) to the
      cell. Therefore, the power of the technology is limited to strains that are
      engineered to express Cas9 and gRNA. To overcome such limitations, we developed a
      simple and universal CRISPR-Cas9 system for gene deletion that works across
      different genetic backgrounds of A. fumigatus. The system employs in vitro
      assembly of dual Cas9 ribonucleoproteins (RNPs) for targeted gene deletion.
      Additionally, our CRISPR-Cas9 system utilizes 35 to 50 bp of flanking regions for
      mediating homologous recombination at Cas9 double-strand breaks (DSBs). As a
      proof of concept, we first tested our system in the DeltaakuB (DeltaakuBku80 )
      laboratory strain and generated high rates (97%) of gene deletion using 2 ug of
      the repair template flanked by homology regions as short as 35 bp. Next, we
      inspected the portability of our system across other genetic backgrounds of A.
      fumigatus, namely, the wild-type strain Af293 and a clinical isolate, A.
      fumigatus DI15-102. In the Af293 strain, 2 ug of the repair template flanked by
      35 and 50 bp of homology resulted in highly efficient gene deletion (46% and 74%,
      respectively) in comparison to classical gene replacement systems. Similar
      deletion efficiencies were also obtained in the clinical isolate DI15-102. Taken
      together, our data show that in vitro-assembled Cas9 RNPs coupled with
      microhomology repair templates are an efficient and universal system for gene
      manipulation in A. fumigatus. IMPORTANCE Tackling the multifactorial nature of
      virulence and antifungal drug resistance in A. fumigatus requires the mechanistic
      interrogation of a multitude of genes, sometimes across multiple genetic
      backgrounds. Classical fungal gene replacement systems can be laborious and time
      consuming and, in wild-type isolates, are impeded by low rates of homologous
      recombination. Our simple and universal CRISPR-Cas9 system for gene manipulation
      generates efficient gene targeting across different genetic backgrounds of A.
      fumigatus. We anticipate that our system will simplify genome editing in A.
      fumigatus, allowing for the generation of single- and multigene knockout
      libraries. In addition, our system will facilitate the delineation of virulence
      factors and antifungal drug resistance genes in different genetic backgrounds of
      A. fumigatus.

PMID- 29202041
TI  - Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika
      Virus Infection.
AB  - Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne
      virus that has been implicated in the surge of the number of microcephaly
      instances in South America. The recent rapid spread of the virus led to its
      declaration as a global health emergency by the World Health Organization. The
      virus is transmitted mainly by the mosquito Aedes aegypti, which is also the
      vector of dengue virus; however, little is known about the interactions of the
      virus with the mosquito vector. In this study, we investigated the transcriptome
      profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7,
      and 14 days postinfection using transcriptome sequencing. Results showed changes
      in the abundance of a large number of transcripts at each time point following
      infection, with 18 transcripts commonly changed among the three time points. Gene
      ontology analysis revealed that most of the altered genes are involved in
      metabolic processes, cellular processes, and proteolysis. In addition, 486 long
      intergenic noncoding RNAs that were altered upon ZIKV infection were identified.
      Further, we found changes of a number of potential mRNA target genes correlating
      with those of altered host microRNAs. The outcomes provide a basic understanding
      of A. aegypti responses to ZIKV and help to determine host factors involved in
      replication or mosquito host antiviral response against the virus. IMPORTANCE
      Vector-borne viruses pose great risks to human health. Zika virus has recently
      emerged as a global threat, rapidly expanding its distribution. Understanding the
      interactions of the virus with mosquito vectors at the molecular level is vital
      for devising new approaches in inhibiting virus transmission. In this study, we
      embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to
      Zika virus infection. Results showed large changes in both coding and long
      noncoding RNAs. Analysis of these genes showed similarities with other
      flaviviruses, including dengue virus, which is transmitted by the same mosquito
      vector. The outcomes provide a global picture of changes in the mosquito vector
      in response to Zika virus infection.

PMID- 29202042
TI  - Relative Impact of Complement Receptors CD21/35 (Cr2/1) on Scrapie Pathogenesis
      in Mice.
AB  - Complement receptors 1 and 2 (CR1/2 or CD35/CD21) recognize complement-opsonized
      antigens to initiate innate and adaptive immunity, respectively. CD35 stimulates
      phagocytosis on macrophages and antigen presentation on follicular dendritic
      cells (FDCs). CD21 helps activate B cells as part of the B cell coreceptor with
      CD19 and CD81. Differential splicing of transcripts from the mouse Cr2 gene
      generates isoforms with both shared and unique complement binding capacities and
      cell-type expression. In mouse models, genetic depletion of Cr2 causes either a
      delay or complete prevention of prion disease, but the relative importance of
      CD35 versus CD21 in promoting prion disease remains unknown. Here we show that
      both isoforms act as high-affinity cell surface prion receptors. However, mice
      lacking CD21 succumbed to terminal prion disease significantly later than mice
      lacking CD35 or wild-type and hemizygous mice. CD21-deficient mice contained
      fewer splenic prions than CD35 knockout mice early after infection that
      contributed to delayed prion neuroinvasion and terminal disease, despite forming
      follicular networks closer to proximal nerves. While we observed no difference in
      B cell networks, PrPC expression, or number of follicles, CD21-deficient mice
      formed more fragmented, less organized follicular networks with fewer Mfge8
      positive FDCs and/or tingible body macrophages (TBMphis) than wild-type or CD35
      deficient mice. In toto, these data demonstrate a more prominent role for CD21
      for proper follicular development and organization leading to more efficient
      lymphoid prion replication and expedited prion disease than in mice expressing
      the CD35 isoform. IMPORTANCE Mammalian prion diseases are caused by prions,
      unique infectious agents composed primarily, if not solely, of a pathologic,
      misfolded form of a normal host protein, the cellular prion protein (PrPC).
      Prions replicate without a genetic blueprint, but rather contact PrPC and coerce
      it to misfold into more prions, which cause neurodegeneration akin to other
      protein-misfolding diseases like Alzheimer's disease. A single gene produces two
      alternatively spliced mRNA transcripts that encode mouse complement receptors
      CD21/35, which promote efficient prion replication in the lymphoid system and
      eventual movement to the brain. Here we show that CD21/35 are high-affinity prion
      receptors, but mice expressing only CD21 die from prion disease sooner than CD35
      expressing mice, which contain less prions early after infection and exhibit
      delayed terminal disease, likely due to their less organized splenic follicles.
      Thus, CD21 appears to be more important for defining splenic architecture that
      influences prion pathogenesis.

PMID- 29202044
TI  - Faecalibacterium Gut Colonization Is Accelerated by Presence of Older Siblings.
AB  - Faecalibacterium prausnitzii is a highly abundant human gut microbe in healthy
      individuals, but it is present at reduced levels in individuals with
      gastrointestinal inflammatory diseases. It has therefore been suggested to
      constitute a marker of a healthy gut and is associated with anti-inflammatory
      properties. However, factors affecting the colonization of F. prausnitzii in the
      human gut during early life are very poorly understood. By analysis of 16S rRNA
      amplicon sequencing data from three separate infant study populations, we
      determined the colonization dynamics of Faecalibacterium and factors affecting
      its establishment in the gut. We found that in particular, the presence of older
      siblings was consistently associated with Faecalibacterium gut colonization
      during late infancy and conclude that acquisition of Faecalibacterium is very
      likely to be accelerated through transfer between siblings.
      IMPORTANCEFaecalibacterium prausnitzii has been suggested to constitute a key
      marker of a healthy gut, yet the factors shaping the colonization of this highly
      oxygen-sensitive, non-spore-forming species in the intestinal environment remain
      poorly understood. Here, we provide evidence from three separate infant study
      populations that F. prausnitzii colonization in the gut happens during late
      infancy and is affected by the number of older siblings in the family. We
      conclude that Faecalibacterium acquisition is highly likely to be accelerated by
      contact between siblings. Bearing in mind the immunoregulatory properties of F.
      prausnitzii and the well-established protective effects against allergic
      disorders related to the presence of older siblings, early colonization of this
      species may have profound consequences for child health.

PMID- 29202043
TI  - Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during
      Primary B-Cell Transformation into Lymphoblastoid Cell Lines.
AB  - Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms
      primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model
      for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic
      aggregation, indicating that EBV induces molecules that mediate cell-cell
      adhesion. We report that EBV potently induced expression of the adhesion molecule
      CD226, which is not normally expressed on B cells. We found that early after
      infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein
      expression. CD226 levels increased further from early proliferating EBV-positive
      B cells to LCLs. We found that CD226 expression on B cells was independent of B
      cell activation as CpG DNA failed to induce CD226 to the extent of EBV infection.
      CD226 expression was high in EBV-infected B cells expressing the latency III
      growth program, but low in EBV-negative and EBV latency I-infected B-lymphoma
      cell lines. We validated this correlation by demonstrating that the latency III
      characteristic EBV NF-kappaB activator, latent membrane protein 1 (LMP1), was
      sufficient for CD226 upregulation and that CD226 was more highly expressed in
      lymphomas with increased NF-kappaB activity. Finally, we found that CD226 was not
      important for LCL steady-state growth, survival in response to apoptotic stress,
      homotypic aggregation, or adhesion to activated endothelial cells. These findings
      collectively suggest that EBV induces expression of a cell adhesion molecule on
      primary B cells that may play a role in the tumor microenvironment of EBV
      associated B-cell malignancies or facilitate adhesion in the establishment of
      latency in vivo. IMPORTANCE Epstein-Barr virus (EBV) is a common human
      herpesvirus that establishes latency in B cells. While EBV infection is
      asymptomatic for most individuals, immune-suppressed individuals are at
      significantly higher risk of a form of EBV latent infection in which infected B
      cells are reactivated, grow unchecked, and generate lymphomas. This form of
      latency is modeled in the laboratory by infecting B cells from the blood of
      normal human donors in vitro. In this model, we identified a protein called CD226
      that is induced by EBV but is not normally expressed on B cells. Rather, it is
      known to play a role in aggregation and survival signaling of non-B cells in the
      immune system. Cultures of EBV-infected cells adhere to one another in "clumps,"
      and while the proteins that are responsible for this cellular aggregation are not
      fully understood, we hypothesized that this form of cellular aggregation may
      provide a survival advantage. In this article, we characterize the mechanism by
      which EBV induces this protein and its expression on lymphoma tissue and cell
      lines and characterize EBV-infected cell lines in which CD226 has been knocked
      out.

PMID- 29202046
TI  - Two Phosphoglucomutase Paralogs Facilitate Ionophore-Triggered Secretion of the
      Toxoplasma Micronemes.
AB  - Paralogs of the widely prevalent phosphoglucomutase (PGM) protein called
      parafusin function in calcium (Ca2+)-mediated exocytosis across eukaryotes. In
      Toxoplasma gondii, the parafusin-related protein 1 (PRP1) has been associated
      with Ca2+-dependent microneme organelle secretion required for essential
      processes like host cell invasion and egress. Using reverse genetics, we observed
      PRP1 to be dispensable for completion of the lytic cycle, including host cell
      invasion and egress by the parasite. However, the absence of the gene affected
      increased microneme release triggered by A23187, a Ca2+ ionophore used to raise
      the cytoplasmic Ca2+ concentration mimicking the physiological role of Ca2+
      during invasion and egress. The basal levels of constitutive microneme release in
      extracellular parasites and phosphatidic acid-triggered microneme secretion were
      unaffected in the mutant. The phenotype of the deletion mutant of the second PGM
      encoding gene in Toxoplasma, PGM2, was similar to the phenotype of the PRP1
      deletion mutant. Furthermore, the ability of the tachyzoites to induce acute
      infection in the mice remained normal in the absence of both PGM paralogs. Our
      data thus reveal that the microneme secretion upon high Ca2+ flux is facilitated
      by the Toxoplasma PGM paralogs, PRP1 and PGM2. However, this protein-mediated
      release is neither essential for lytic cycle completion nor for acute virulence
      of the parasite. IMPORTANCE Ca2+-dependent exocytosis is essential for the life
      cycle of apicomplexan parasites. Toxoplasma gondii harbors a phosphoglucomutase
      (PGM) ortholog, PRP1, previously associated with Ca2+-dependent microneme
      secretion. Here it is shown that genetic deletion of either PRP1, its PGM2
      ortholog, or both genes is dispensable for the parasite's lytic cycle, including
      host cell egress and invasion. Depletion of the proteins abrogated high Ca2+
      mediated microneme secretion induced by the ionophore A23187; however, the
      constitutive and phosphatidic acid-mediated release remained unaffected.
      Secretion mediated by the former pathway is not essential for tachyzoite survival
      or acute in vivo infection in the mice.

PMID- 29202047
TI  - Subgingival Microbiome Colonization and Cytokine Production during Early Dental
      Implant Healing.
AB  - Little is known about longitudinal development of the peri-implant subgingival
      microbiome and cytokine production as a new sulcus forms after dental implant
      placement. Therefore, the purpose of this observational study was to evaluate
      simultaneous longitudinal changes in the oral microbiome and cytokine production
      in the developing peri-implant sulcus compared to control natural teeth. Four and
      12 weeks after implant placement and abutment connection, a dental implant and a
      natural tooth were sampled in 25 patients for subgingival plaque and gingival
      crevicular fluid (GCF [around teeth] and peri-implant crevicular fluid [PICF]
      around implants). DNA from plaque samples was extracted and sequenced using
      Illumina-based 16S rRNA sequencing. GCF and PICF samples were analyzed using a
      customized Milliplex human cytokine and chemokine magnetic bead panel. Beta
      diversity analysis revealed that natural teeth and implants had similar
      subgingival microbiomes, while teeth had greater alpha diversity than implants.
      At the genus level, however, few differences were noted between teeth and dental
      implants over 12 weeks. Specifically, Actinomyces and Selenomonas were
      significantly elevated around teeth versus dental implants at both 4 weeks and 12
      weeks, while Corynebacterium and Campylobacter were significantly elevated only
      at 4 weeks around teeth. The only difference between PICF and GCF biomarkers was
      significantly elevated granulocyte-macrophage colony-stimulating factor levels
      around teeth versus dental implants at the 4-week visit. The subgingival
      microbiome and cytokine production were similar between teeth and implants during
      early healing, suggesting that these profiles are driven by the patient following
      dental implant placement and are not determined by anatomical niche. IMPORTANCE
      Dental implants are a common treatment option offered to patients for tooth
      replacement. However, little is known regarding initial colonization of the
      subgingival microbiome and simultaneous longitudinal cytokine production in
      humans during the early healing phase following implant placement. We report
      findings from an in vivo study that assessed initial colonization of the
      subgingival microbiome and concomitant early cytokine production in a newly
      formed anatomical space, namely, an implant sulcus. This approach may be useful
      in future interventional studies to influence dental implant success. Our data
      showed that the subgingival microbiome and cytokine profile were similar for
      control natural teeth and dental implants at both 4 and 12 weeks after implant
      placement. These data suggest that these profiles are driven by the patient and
      not by anatomical location (i.e., tooth versus dental implant).

PMID- 29202045
TI  - Adaptation in a Fibronectin Binding Autolysin of Staphylococcus saprophyticus.
AB  - Human-pathogenic bacteria are found in a variety of niches, including free
      living, zoonotic, and microbiome environments. Identifying bacterial adaptations
      that enable invasive disease is an important means of gaining insight into the
      molecular basis of pathogenesis and understanding pathogen emergence.
      Staphylococcus saprophyticus, a leading cause of urinary tract infections, can be
      found in the environment, food, animals, and the human microbiome. We identified
      a selective sweep in the gene encoding the Aas adhesin, a key virulence factor
      that binds host fibronectin. We hypothesize that the mutation under selection
      (aas_2206A>C) facilitates colonization of the urinary tract, an environment where
      bacteria are subject to strong shearing forces. The mutation appears to have
      enabled emergence and expansion of a human-pathogenic lineage of S.
      saprophyticus. These results demonstrate the power of evolutionary genomic
      approaches in discovering the genetic basis of virulence and emphasize the
      pleiotropy and adaptability of bacteria occupying diverse niches.
      IMPORTANCEStaphylococcus saprophyticus is an important cause of urinary tract
      infections (UTI) in women; such UTI are common, can be severe, and are associated
      with significant impacts to public health. In addition to being a cause of human
      UTI, S. saprophyticus can be found in the environment, in food, and associated
      with animals. After discovering that UTI strains of S. saprophyticus are for the
      most part closely related to each other, we sought to determine whether these
      strains are specially adapted to cause disease in humans. We found evidence
      suggesting that a mutation in the gene aas is advantageous in the context of
      human infection. We hypothesize that the mutation allows S. saprophyticus to
      survive better in the human urinary tract. These results show how bacteria found
      in the environment can evolve to cause disease.

PMID- 29202048
TI  - Making It Last: Storage Time and Temperature Have Differential Impacts on
      Metabolite Profiles of Airway Samples from Cystic Fibrosis Patients.
AB  - Metabolites of human or microbial origin have the potential to be important
      biomarkers of the disease state in cystic fibrosis (CF). Clinical sample
      collection and storage conditions may impact metabolite abundances with clinical
      relevance. We measured the change in metabolite composition based on untargeted
      gas chromatography-mass spectrometry (GC-MS) when CF sputum samples were stored
      at 4 degrees C, -20 degrees C, or -80 degrees C with one or two freeze-thaw
      cycles. Daily measurements were taken for 1 week and then weekly for 4 weeks (4
      degrees C) and 8 weeks (-20 degrees C). The metabolites in samples stored at -20
      degrees C maintained abundances similar to those found at-80 degrees C over the
      course of 8 weeks (average change in Bray-Curtis distance, 0.06 +/- 0.04) and
      were also stable after one or two freeze-thaw cycles. However, the metabolite
      profiles of samples stored at 4 degrees C shifted after 1 day and continued to
      change over the course of 4 weeks (average change in Bray-Curtis distance, 0.31
      +/- 0.12). The abundances of several amino acids and other metabolites increased
      with time of storage at 4 degrees C but remained constant at -20 degrees C.
      Storage temperature was a significant factor driving the metabolite composition
      (permutational multivariate analysis of variance: r2 = 0.32 to 0.49, P < 0.001).
      CF sputum samples stored at -20 degrees C at the time of sampling maintain a
      relatively stable untargeted GC-MS profile. Samples should be frozen on the day
      of collection, as more than 1 day at 4 degrees C impacts the global composition
      of the metabolites in the sample. IMPORTANCE Metabolomics has great potential for
      uncovering biomarkers of the disease state in CF and many other contexts.
      However, sample storage timing and temperature may alter the abundance of
      clinically relevant metabolites. To assess whether existing samples are stable
      and to direct future study design, we conducted untargeted GC-MS metabolomic
      analysis of CF sputum samples after one or two freeze-thaw cycles and storage at
      4 degrees C and -20 degrees C for 4 to 8 weeks. Overall, storage at -20 degrees C
      and freeze-thaw cycles had little impact on metabolite profiles; however, storage
      at 4 degrees C shifted metabolite abundances significantly. GC-MS profiling will
      aid in our understanding of the CF lung, but care should be taken in studies
      using sputum samples to ensure that samples are properly stored.

PMID- 29202049
TI  - The odyssey of linking to and staying in HIV care among male sex workers in Peru.
AB  - Background: In Peru, there is little information about the HIV care continuum.
      Therefore, we conducted a study to describe the HIV care continuum among male sex
      workers (MSWs) in Lima. Methods: We applied close-ended surveys with 209 MSWs
      about their engagement in the HIV care continuum and open-ended surveys with 34
      MSWs who are people living with HIV (PLHIV) to explore their linkage to and
      retention in HIV care. Results: Of 209 MSWs, only 71% (n=148) reported a lifetime
      HIV test and 56% (n=116) of all MSWs received confirmatory HIV test results. Of
      the 34 MSWs who are PLHIV, 76% had received HIV care at least once, but only 59%
      were currently in care, 50% were currently taking ART(antiretroviral therapy) and
      an even lower 32% had been on ART for 6 months or more. The primary reason for
      non-linkage to HIV care is the multiple visits to link at the Ministry of Health
      (MOH). Remaining in care was also challenging, particularly at non-governmental
      organizations (NGOs). Conclusions: Substantial barriers linking to and remaining
      in HIV care result in significant delays in linkage and high proportions of PLHIV
      that remain unlinked or become unstably linked following initial linkage. Urgent
      implementation science research is needed to facilitate linkage to HIV care and
      strengthen retention in HIV care post-linkage.

PMID- 29202050
TI  - One Size Doesn't Fit All: Measuring Individual Privacy in Aggregate Genomic Data.
AB  - Even in the aggregate, genomic data can reveal sensitive information about
      individuals. We present a new model-based measure, PrivMAF, that provides
      provable privacy guarantees for aggregate data (namely minor allele frequencies)
      obtained from genomic studies. Unlike many previous measures that have been
      designed to measure the total privacy lost by all participants in a study,
      PrivMAF gives an individual privacy measure for each participant in the study,
      not just an average measure. These individual measures can then be combined to
      measure the worst case privacy loss in the study. Our measure also allows us to
      quantify the privacy gains achieved by perturbing the data, either by adding
      noise or binning. Our findings demonstrate that both perturbation approaches
      offer significant privacy gains. Moreover, we see that these privacy gains can be
      achieved while minimizing perturbation (and thus maximizing the utility) relative
      to stricter notions of privacy, such as differential privacy. We test PrivMAF
      using genotype data from the Wellcome Trust Case Control Consortium, providing a
      more nuanced understanding of the privacy risks involved in an actual genome-wide
      association studies. Interestingly, our analysis demonstrates that the privacy
      implications of releasing MAFs from a study can differ greatly from individual to
      individual. An implementation of our method is available at
      http://privmaf.csail.mit.edu.

PMID- 29202051
TI  - A new platform for global health research and policy exchange and communication.
AB  - Peer-reviewed publications are essential to promote the development of global
      health sciences. Wuhan University Global Health Institute, in partnership with
      BioMed Central, launches Global Health Research and Policy (GHRP) as an open
      access journal to meet the needs of all authors and readers who are interested in
      global health. Our publication priorities include both empirical and
      implementation research, research methodologies, and global health education, as
      well as opinions and discussion over the concept of global health sciences and
      its development in the future.

PMID- 29202052
TI  - Moving from medical to health systems classifications of deaths: extending verbal
      autopsy to collect information on the circumstances of mortality.
AB  - Background: Verbal autopsy (VA) is a health surveillance technique used in low
      and middle-income countries to establish medical causes of death (CODs) for
      people who die outside hospitals and/or without registration. By virtue of the
      deaths it investigates, VA is also an opportunity to examine social exclusion
      from access to health systems. The aims were to develop a system to collect and
      interpret information on social and health systems determinants of deaths
      investigated in VA. Methods: A short set of questions on care pathways,
      circumstances and events at and around the time of death were developed and
      integrated into the WHO 2012 short form VA (SF-VA). Data were subsequently
      analysed from two census rounds in the Agincourt Health and Socio-Demographic
      Surveillance Site (HDSS), South Africa in 2012 and 2013 where the SF-VA had been
      applied. InterVA and descriptive analysis were used to calculate cause-specific
      mortality fractions (CSMFs), and to examine responses to the new indicators and
      whether and how they varied by medical CODs and age/sex sub-groups. Results: One
      thousand two hundred forty-nine deaths were recorded in the Agincourt HDSS
      censuses in 2012-13 of which 1,196 (96 %) had complete VA data. Infectious and
      non-communicable conditions accounted for the majority of deaths (47 % and 39 %
      respectively) with smaller proportions attributed to external, neonatal and
      maternal causes (5 %, 2 % and 1 % respectively). 5 % of deaths were of
      indeterminable cause. The new indicators revealed multiple problems with access
      to care at the time of death: 39 % of deaths did not call for help, 36 % found
      care unaffordable overall, and 33 % did not go to a facility. These problems were
      reported consistently across age and sex sub-groups. Acute conditions and younger
      age groups had fewer problems with overall costs but more with not calling for
      help or going to a facility. An illustrative health systems interpretation
      suggests extending and promoting existing provisions for transport and financial
      access in this setting. Conclusions: Supplementing VA with questions on the
      circumstances of mortality provides complementary information to CSMFs relevant
      for health planning. Further contextualisation of the method and results are
      underway with health systems stakeholders to develop the interpretation sequence
      as part of a health policy and systems research approach.

PMID- 29202053
TI  - Protection motivation theory and cigarette smoking among vocational high school
      students in China: a cusp catastrophe modeling analysis.
AB  - Background: Tobacco use is one of the greatest public health problems worldwide
      and the hazards of cigarette smoking to public health call for better recognition
      of cigarette smoking behaviors to guide evidence-based policy. Protection
      motivation theory (PMT) provides a conceptual framework to investigate tobacco
      use. Evidence from diverse sources implies that the dynamics of smoking behavior
      may be quantum in nature, consisting of an intuition and an analytical process,
      challenging the traditional linear continuous analytical approach. In this study,
      we used cusp catastrophe, a nonlinear analytical approach to test the dual
      process hypothesis of cigarette smoking. Methods: Data were collected from a
      random sample of vocational high school students in China (n = 528). The
      multivariate stochastic cusp modeling was used and executed with the Cusp Package
      in R. The PMT-based Threat Appraisal and Coping Appraisal were used as the two
      control variables and the frequency of cigarette smoking (daily, weekly,
      occasional, and never) in the past month was used as the outcome variable.
      Results: Consistent with PMT, the Threat Appraisal (asymmetry, alpha1 = 0.1987, p
      < 0.001) and Coping Appraisal (bifurcation, beta2 = 0.1760, p < 0.05)
      significantly predicted the smoking behavior after controlling for covariates.
      Furthermore, the cusp model performed better than the alternative linear and
      logistic regression models with regard to higher R2 (0.82 for cusp, but 0.21 for
      linear and 0.25 for logistic) and smaller AIC and BIC. Conclusion: Study findings
      support the conclusion that cigarette smoking in adolescents is a quantum process
      and PMT is relevant to guide studies to understand smoking behavior for smoking
      prevention and cessation.

PMID- 29202054
TI  - Dilemma of healthcare reform and invention of new discipline of health fiscalogy.
AB  - Background: China's Reform and Open up Policy in 1980s has brought rapid economic
      development to Chinese society. With the deepening of economic reform, the
      withdrawal of the state in China has had visible and worrisome consequences for
      health and for the functioning of health services. The new round of healthcare
      reform after 2009 has made significant achievements on improving fundamental
      health and bringing back the nature of welfare of health. However, the financing
      mechanism of health system has not been established, and the underlying reason
      behind the healthcare reform dilemma and the theoretical solution need to be
      found. Methods: This study used the methods of literature review, theoretical
      research and comparative research to summarize and analyze the reasons and
      solutions of current dilemma in healthcare reform, and created the new discipline
      of health fiscalogy through theoretical analysis and vertical and horizontal
      comparison of healthcare system, especially health financing. Results: Dilemma in
      healthcare system emerged from the circumstances of rapid process of
      industrialization, urbanization and population aging, including the profit-driven
      phenomena, tendency of excessive marketization in public hospitals, strained
      doctor-patient relationship, high disease burden on individuals and families, and
      so on. It can be concluded that the theoretical basis of healthcare system and
      the nature of health resources are crucial in solving the dilemma of healthcare
      reform. The theoretical basis of healthcare reform should be health fiscalogy
      focusing on government as the main body of health care responsibility rather than
      health economics focusing on anti-monopoly. There are two key differences between
      health economics and health fiscalogy: responsible person/department of disease
      and health welfare, and nature of resource. The new discipline of health
      fiscalogy has universal and important implications on both China's healthcare
      reform and the healthcare reform in the world. Conclusions: China's healthcare
      reform should return from the paradigm of health economics and marketization
      financing model to the paradigm of health fiscalogy and government-led financing
      model, which is reflected in the main position of government and social welfare.

PMID- 29202055
TI  - Determinants of patient survival during the 2014 Ebola Virus Disease outbreak in
      Bong County, Liberia.
AB  - Background: The unprecedented size of the 2014 Ebola Virus Disease (EVD) outbreak
      in West Africa has allowed for a more extensive characterization of the clinical
      presentation and management of this disease. In this study, we report the trends
      in morbidity, mortality, and determinants of patient survival as EVD spread into
      Bong County, Liberia. Methods: An analysis of suspected, probable, or confirmed
      cases of EVD (n = 607) reported to the Liberian Ministry of Health and Social
      Welfare (MOHSW) between March 23rd and December 31st 2014 was conducted. The
      likelihood of infection given exposure factors was determined using logistic
      regression in individuals with a definitive diagnosis by RT-PCR (n = 321). The
      risk of short-term mortality (30 days) given demographic factors, clinical
      symptoms, and highest level of treatment received was assessed with Cox
      regression and survival analyses (n = 391). Results: The overall mortality rate
      was 53.5 % (95 % CI: 49 %, 58 %) and decreased as access to medical treatment
      increased. Those who reported contact with another EVD case were more likely to
      be infected (OR: 5.7), as were those who attended a funeral (OR: 3.9). Mortality
      increased with age (P < 0.001) and was higher in males compared to females (P
      =0.006). Fever (HR: 6.63), vomiting (HR: 1.93), diarrhea (HR: 1.99), and
      unexplained bleeding (HR: 2.17) were associated with increased mortality. After
      adjusting for age, hospitalized patients had a 74 % reduction in the risk of
      short term mortality (P < 0.001 AHR: 0.26; 95 % CI AHR: 0.18, 0.37), compared to
      those not given medical intervention. Conclusion: Even treatment with only basic
      supportive care such as intravenous rehydration therapy was able to significantly
      improve patient survival in suspected, probable, or confirmed EVD cases.

PMID- 29202056
TI  - Taking action on violence through research, policy, and practice.
AB  - Background: Violence is a critical public health problem associated with
      compromised health and social suffering that are preventable. The Centre for
      Global Health and Health Equity organized a forum in 2014 to identify: (1)
      priority issues related to violence affecting different population groups in
      Canada, and (2) strategies to take action on priority issues to reduce violence
      related health inequities in Canada. In this paper, we present findings from the
      roundtable discussions held at the Forum, offer insights on the socio-political
      implications of these findings, and provide recommendations for action to reduce
      violence through research, policy and practice. Methods: Over 60 academic
      researchers, health and social service agency staff, community advocates and
      graduate students attended the daylong Forum, which included presentations on
      structural violence, community violence, gender-based violence, and violence
      against marginalized groups. Detailed notes taken at the roundtables were
      analyzed by the first author using a thematic analysis technique. Findings: The
      thematic analysis identified four thematic areas: 1) structural violence
      perpetuates interpersonal violence - the historical, social, political and
      economic marginalization that contributes to personal and community violence. 2)
      social norms of gender-based violence-the role of dominant social norms in
      perpetuating the practice of violence, especially towards women, children and
      older adults; 3) violence prevention and mitigation programs-the need for policy
      and programming to address violence at the individual/interpersonal, community,
      and societal levels; and 4) research gaps-the need for comprehensive research
      evidence made up of systematic reviews, community-based intervention and
      evaluation of implementation research to identify effective programming to
      address violence. Conclusions: The proceedings from the Global Health and Health
      Equity Forum underscored the importance of recognizing violence as a public
      health issue that requires immediate and meaningful communal and structural
      investment to break its historic cycles. Based on our thematic analysis and
      literature review, four recommendations are offered: (1) Support and adopt
      policies to prevent or reduce structural violence; (2) Adopt multi-pronged
      strategies to transform dominant social norms associated with violence; (3)
      Establish standards and ensure adequate funding for violence prevention programs
      and services; and (4) Fund higher level ecological research on violence
      prevention and mitigation.

PMID- 29202058
TI  - Shifts in endocrine homeostasis and preventive hormone replacement therapy:
      extending the Women's Health Initiative globally.
AB  - Background: Reducing disease risk for women after menopause is global health
      issue. A major portion of the Women's Health Initiative (WHI) consisted of two
      clinical trials involving 161,809 post-menopausal women aged 50-79 that tested
      the effect of hormone replacement therapy (HRT) on reducing cardiovascular
      disease and other secondary outcomes. Previous analyses of the data reveal that
      HRT should not be recommended for post-menopausal women, but show potential
      benefits for younger women. Thus, there may be a critical period just prior to or
      during the early stages of menopause where HRT could be both safe and beneficial.
      Main body: Menopause marks the beginning of a process of non-reversible reduction
      in estrogen by which estrogen levels decline progressively, followed by a
      reduction in estrogen receptors. This results in periods of hormone-receptor
      imbalances, exacerbating the effects of lower serum estrogen and is considered
      the primarily endocrinal source of menopause symptoms. Eventually a hormone
      receptor balance is achieved at a lower level.Here, we purport that the negative
      outcomes from WHI trials were primarily due to the fact preventive HRT was
      initiated in women who had already achieved hormone-receptor equilibrium at lower
      hormonal levels. Conclusion: We argue for further HRT clinical trials in women at
      varying stages of menopause, including pre-menopause and early menopause, and in
      women from different countries. Variation across countries and subgroups in how
      women experience menopause and perceive menopause symptoms suggest that
      biocultural differences should be considered in both study design and measurement
      approaches to test the effectiveness of HRT. Particularly, we recommend
      longitudinal studies to assess changes in hormonal level over time, and to detect
      the "most effective period" for HRT to reduce health risk for women going through
      the whole menopause period.

PMID- 29202057
TI  - Potentially traumatic events, coping strategies and associations with mental
      health and well-being measures among conflict-affected youth in Eastern
      Democratic Republic of Congo.
AB  - Background: Youth in conflict and post-conflict settings are exposed to a variety
      of potentially-traumatic events that impact their mental health and well-being.
      The purposes of this study were to examine coping strategies among conflict
      affected youth exposed to potentially-traumatic events and the relationship to
      psychological symptoms and well-being in the Democratic Republic of Congo (DRC).
      Methods: A total of 434 male and female youth (ages 10-15 years) completed data
      collection with a trained Congolese interviewer. The survey instrument included
      measures of exposure to potentially traumatic events, an adapted coping
      strategies checklist, and measures of psychosocial distress and well-being.
      Exploratory factor analyses was used to identify coping strategies and
      Hierarchical regression was used to assess how coping strategies were associated
      with psychological symptoms including internalizing and externalizing problems
      and well-being outcomes including prosocial behavior and self-esteem. Results:
      Exploratory Factor analysis suggested four coping strategies; problem-focused,
      emotion-focused, avoidance and faith-based strategies. Problem-focused coping
      strategies were associated with greater internalizing and externalizing problems
      and lower prosocial behavior in both boys and girls. However, when problem
      focused strategies were used with emotion-focused coping strategies, the result
      was fewer internalizing problems in girls and fewer externalizing problems in
      boys and girls. Emotion-focused, avoidance and faith based strategies were
      associated with better self-esteem. Conclusion: These results suggest a complex
      relationship between coping strategies, psychological symptoms and well-being and
      contradict evidence that problem-focused strategies benefit mental health while
      emotion-focused strategies harm mental health, particularly in conflict and post
      conflict settings. The results suggest coping flexibility, or use of multiple
      coping strategies may be particularly useful to improving mental health and well
      being. The need for context specific understandings of coping strategies in
      conflict-affected populations is highlighted by the results of the study.

PMID- 29202059
TI  - Community-based management versus traditional hospitalization in treatment of
      drug-resistant tuberculosis: a systematic review and meta-analysis.
AB  - Background: Multidrug drug resistant Tuberculosis (MDR-TB) and extensively drug
      resistant Tuberculosis (XDR-TB) have emerged as significant public health threats
      worldwide. This systematic review and meta-analysis aimed to investigate the
      effects of community-based treatment to traditional hospitalization in improving
      treatment success rates among MDR-TB and XDR-TB patients in the 27 MDR-TB High
      burden countries (HBC). Methods: We searched PubMed, Cochrane, Lancet, Web of
      Science, International Journal of Tuberculosis and Lung Disease, and Centre for
      Reviews and Dissemination (CRD) for studies on community-based treatment and
      traditional hospitalization and MDR-TB and XDR-TB from the 27 MDR-TB HBC. Data on
      treatment success and failure rates were extracted from retrospective and
      prospective cohort studies, and a case control study. Sensitivity analysis,
      subgroup analyses, and meta-regression analysis were used to explore bias and
      potential sources of heterogeneity. Results: The final sample included 16 studies
      involving 3344 patients from nine countries; Bangladesh, China, Ethiopia, Kenya,
      India, South Africa, Philippines, Russia, and Uzbekistan. Based on a random
      effects model, we observed a higher treatment success rate in community-based
      treatment (Point estimate = 0.68, 95 % CI: 0.59 to 0.76, p < 0.01) compared to
      traditional hospitalization (Point estimate = 0.57, 95 % CI: 0.44 to 0.69, p <
      0.01). A lower treatment failure rate was observed in community-based treatment 7
      % (Point estimate = 0.07, 95 % CI: 0.03 to 0.10; p < 0.01) compared to
      traditional hospitalization (Point estimate = 0.188, 95 % CI: 0.10 to 0.28; p <
      0.01). In the subgroup analysis, studies without HIV co-infected patients,
      directly observed therapy short course-plus (DOTS-Plus) implemented throughout
      therapy, treatment duration > 18 months, and regimen with drugs >5 reported
      higher treatment success rate. In the meta-regression model, age of patients,
      adverse events, treatment duration, and lost to follow up explains some of the
      heterogeneity of treatment effects between studies. Conclusion: Community-based
      management improved treatment outcomes. A mix of interventions with DOTS-Plus
      throughout therapy and treatment duration > 18 months as well as strategies in
      place for lost to follow up and adverse events should be considered in MDR-TB and
      XDR-TB interventions, as they influenced positively, treatment success.

PMID- 29202060
TI  - Determinants of intentions to quit smoking among adult smokers in Bangladesh:
      findings from the International Tobacco Control (ITC) Bangladesh wave 2 survey.
AB  - Background: With about 22 million adult smokers, Bangladesh needs strong measures
      that would promote smoking cessation. Using data from Wave 2 of the International
      Tobacco Control (ITC) Survey, this study examined the factors associated with
      intention to quit smoking among Bangladeshi smokers. Methods: Data from Wave 2 of
      the International Tobacco Control (ITC) Survey in Bangladesh, a face to face
      survey of adult smokers, were analysed. In the ITC survey, households were
      sampled using a stratified multistage design and interviewed using a structured
      questionnaire. Results: Of the respondents (N = 2982), most were male (96 %),
      married (80 %), and Muslim (83 %); 33 % were illiterate and 54 % were aged below
      40. Almost two-thirds were from areas outside Dhaka, 78 % smoked cigarettes
      exclusively; and 36 % had an intention to quit smoking in the future. This study
      identified several predictors, comparable to other international studies, of
      intention to quit smoking: area of residence, number of cigarettes smoked daily,
      previous quit attempt, visiting a doctor in the past, having child aged 5 or
      below at home, perceived benefit from quitting, being worried about own health,
      knowledge of SHS, not enjoying smoking and workplace smoking policy. Conclusions:
      These findings suggest that the prevalence of intention to quit smoking is lower
      among Bangladeshi smokers than those among smokers in developed countries.
      However, the factors relating to quit intentions among Bangladeshi smokers are
      comparable to those found in Western countries. Population based tobacco control
      programs and policies should consider these predictors in the design of
      interventions to increase quitting among smokers in Bangladesh.

PMID- 29202061
TI  - Medical students' perceptions about the added educational value of student-run
      HIV/AIDS educational campaigns in the Dominican Republic.
AB  - Objective: This purpose of this report was to examine the perceptions of medical
      students about the strengths, limitations, and recommendations for improvement of
      the first known student-run HIV/AIDS educational campaigns in the Dominican
      Republic (DR), as they relate to the added value applied to their educational
      training. Methods: A retrospective review was conducted on evaluation reports
      completed by five medical students who coordinated the implementation of three
      annual HIV/AIDS educational campaigns in five DR communities, between 2012 and
      2014. Thematic analysis was used to identify emerging themes related to perceived
      strengths, limitations, and recommendations for improvement and develop an
      acronym related to program strengths as value added to medical education.
      Results: Students highlighted that program strengths were the use of social media
      technology to facilitate communication and culture-based creativity to capture
      the attention of target audiences; and limitations were inadequate financial
      support and HIV-related cultural stigma, due to lack of disease knowledge and
      awareness or perceived contrasts between the federal system and faith-based
      community. Recommendations for program improvement, such as comprehensive event
      preparation and knowing the target audience, were described as key to maximizing
      the delivery of health messages. Conclusions: Our results highlighted that
      medical students gained expertise in the effective use of social media
      technology, culture-based creativity, and team synergy to disseminate HIV/AIDS
      health information across five DR communities. Students participated in these
      extracurricular community health campaigns, strengthening skills in
      communication, health advocacy, and leadership for their medical training. They
      served as human resources for health and can pave the way as future clinicians
      and indispensable health educators in local and national health collaborations.

PMID- 29202062
TI  - Health system strengthening and hypertension management in China.
AB  - Background: Non-communicable diseases are the leading causes of global burden of
      diseases, and hypertension is one of the most important risk factors.
      Hypertension prevalence doubled in China in the past decade and affects more than
      300 million Chinese people. In the review we systematically searched peer
      reviewed publications that link health system level factors with hypertension
      management in China and provide the current knowledge on how to improve a
      country's health system to manage the hypertension epidemic. Methods: A framework
      was developed to guide the review. The database of PubMed, CNKI were
      systematically searched from inception to April 13, 2016. Two authors
      independently screened the searched results for inclusion, conducted data
      extraction and appraised the quality of studies. Key findings were described
      according to the framework. Findings: Five hundred seventy-two publications were
      identified, where 11 articles were left according to the inclusion and exclusion
      criteria. The study periods range from 2010 to 2015. All about 11 researches
      linked health system factors to the outcome of hypertension management. And the
      outcomes were just focused on the awareness, treatment and control of
      hypertension but not hypertension incidence. One study is about the role of
      health system governance, investigating the performance of different organized
      community health care centers; three studies were about health financing
      comparing differences in insurance coverage; three studies were about health
      information practicing the hypertension guidelines of China or the WHO, and the
      rest three about mechanisms of health service delivery. No researches were
      identified about physical resources for health and human resources for health.
      Conclusions: Hypertension prevalence has been rising rapidly in China and the
      management of hypertension in China is a detection problem rather than treatment
      problem. Limited evidence shows the positive effect of health system factors on
      hypertension management and joint efforts from health system and epidemiological
      researchers are warranted to extend knowledge in this area.

PMID- 29202063
TI  - The global spread of Middle East respiratory syndrome: an analysis fusing
      traditional epidemiological tracing and molecular phylodynamics.
AB  - Background: Since its discovery in 2012, over 1700 confirmed cases of Middle East
      Respiratory Syndrome (MERS) have been documented worldwide and more than a third
      of those cases have died. While the greatest number of cases has occurred in
      Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of
      Korea showed that a pandemic is a possibility that cannot be ignored. Due to the
      deficit of knowledge in transmission methodology, targeted treatment and possible
      vaccines, understanding this virus should be a priority. Our aim was to combine
      epidemiological data from literature with genetic information from viruses
      sequenced around the world to present a phylodynamic picture of MERS spread
      molecular level to global scale. Methods: We performed a qualitative meta
      analysis of all laboratory confirmed cases worldwide to date based on literature,
      with emphasis on international transmission and healthcare associated infections.
      In parallel, we used publicly available MERS-CoV genomes from GenBank to create a
      phylogeographic tree, detailing geospatial timeline of viral evolution. Results:
      Several healthcare associated outbreaks starting with the retrospectively
      identified hospital outbreak in Jordan to the most recent outbreak in Riyadh,
      Saudi Arabia have occurred. MERS has also crossed many oceans, entering multiple
      nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal
      history of MERS cases, as documented epidemiologically, was examined by Bayesian
      phylogenetic analysis. Distribution of sequences into geographic clusters and
      interleaving of MERS-CoV sequences from camels among those isolated from humans
      indicated that multiple zoonotic introductions occurred in endemic nations. We
      also report a summary of basic reproduction numbers for MERS-CoV in humans and
      camels. Conclusion: Together, these analyses can help us identify factors
      associated with viral evolution and spread as well as establish efficacy of
      infection control measures. The results are especially pertinent to countries
      without current MERS-CoV endemic, since their unfamiliarity makes them
      particularly susceptible to uncontrollable spread of a virus that may be imported
      by travelers.

PMID- 29202064
TI  - An instrument based on protection motivation theory to predict Chinese
      adolescents' intention to engage in protective behaviors against schistosomiasis.
AB  - Background: Further advancement in schistosomiasis prevention requires new tools
      to assess protective motivation, and promote innovative intervention program.
      This study aimed to develop and evaluate an instrument developed based on the
      Protection Motivation Theory (PMT) to predict protective behavior intention
      against schistosomiasis among adolescents in China. Methods: We developed the
      Schistosomiasis PMT Scale based on two appraisal pathways of protective
      motivation- threat appraisal pathway and coping appraisal pathway. Data from a
      large sample of middle school students (n = 2238, 51 % male, mean age 13.13 +/-
      1.10) recruited in Hubei, China was used to evaluated the validity and
      reliability of the scale. Results: The final scale contains 18 items with seven
      sub-constructs. Cronbach's Alpha coefficients for the entire instrument was 0.76,
      and for the seven sub-constructs of severity, vulnerability, intrinsic reward,
      extrinsic reward, response efficacy, self-efficacy and response cost was 0.56,
      0.82, 0.75, 0.80, 0.90, 0.72 and 0.70, respectively. The construct validity
      analysis revealed that the one level 7 sub-constructs model fitted data well (GFI
      = 0.98, CFI = 0.98, RMSEA = 0.03, Chi-sq/df = 3.90, p < 0.001). Predictive
      validity showed that both the PMT instrument score and the 7 sub-construct scores
      were significantly correlated with the intention engaged in protective behavior
      against schistosomiasis (p < 0.05). Conclusions: This study provides a reliable
      and valid tool to measure protective motivation in schistosomiasis prevention
      control. Further studies are needed to develop more effective intervention
      programs for schistosomiasis prevention.

PMID- 29202065
TI  - Dengue fever outbreaks in Eritrea, 2005-2015: A case for strengthening
      surveillance, control and reporting.
AB  - Background: The geographic distribution and burden of dengue is increasing
      globally. This study aims to evaluate dengue outbreaks and to substantiate the
      need for strengthened surveillance, reporting and control in Eritrea. Methods:
      Data from two cross-sectional dengue epidemic investigations in 2005 and 2010
      were analyzed. Samples were tested for dengue virus-specific IgM and IgG
      antibodies using capture enzyme-linked immunosorbent assays. Dengue vectors'
      breeding attributes were characterized and epidemic risk indices determined.
      National routine surveillance weekly reports from 2005 to the second quarter of
      2015 were analyzed for spatiotemporal trends. Results: Dengue outbreaks increased
      in Eritrea from 2005 to 2015 with clinical presentation varying markedly among
      patients. The house and container indices for Aedes aegypti were 40 and 39.6 %
      respectively, with containers having A. aeqypti varying significantly (P < 0.04).
      Serum from 33.3 % (n = 15) and 88 % (n = 26) of clinical dengue cases in Aroget
      sub-Zoba (district) of Gash Barka Zoba (region) contained anti-DENV IgM antibody
      in 2005 and 2006, respectively. The national surveillance data from 2005 to 2015
      indicate an overall spatiotemporal increase of dengue fever. Conclusions: The
      increase in dengue outbreaks has been confirmed in Eritrea and necessitates
      strengthening of surveillance and health worker and laboratory capacity, as well
      as targeted vector control interventions.

PMID- 29202066
TI  - Factors contributing to low uptake and renewal of health insurance: a qualitative
      study in Ghana.
AB  - Background: The effort to expand access to healthcare and reduce health
      inequalities in many low income countries have meant that many have adopted
      different levels of social health protection mechanisms. Ghana introduced a
      National Health Insurance Scheme (NHIS) in 2005 with the aim of removing previous
      barriers created by the user fees financing system. Although the NHIS has made
      health accessible to some category of people, the majority of Ghanaians (60 %)
      are not enroled on the scheme. Earlier studies have looked at various factors
      that account for this low uptake. However, we recognise that this qualitative
      study will nuance the depth of these barriers to enrolment. Methods: Minimally
      structured, qualitative interviews were conducted with key stakeholders at the
      district, regional and national levels. Focus group discussions were also
      undertaken at the community level. Using an inductive and content analytic
      approach, the transcripts were analyzed to identify and define categories that
      explain low uptake of health insurance. Results: The results are presented under
      two broad themes: sociocultural and systemic factors. Sociocultural factors
      identified were 1) vulnerability within certain groups such as the aged and the
      disabled groups which impeded access to the NHIS 2) cultural and religious norms
      which discouraged enrolment into the scheme. System-wide factors were 1)
      inadequate distribution of social infrastructure such as healthcare facilities,
      2) weak administrative processes within the NHIS, and 3) poor quality of care.
      Conclusions: Mapping the interplay of these dynamic relations between the NHIS,
      its clients and service providers, the study identifies critical factors at the
      policy-making level, service provider level, and client level (reflective in
      household and community level institutional arrangements) that affect enrolment
      in the scheme. Our findings inform a number of potential reforms in the area of
      distribution of health resources and cost containment to expand coverage,
      increase choices and meeting the needs of the end user.

PMID- 29202067
TI  - Pubertal development and screen time among South Korean adolescents: testing body
      mass index and psychological well-being as mediators.
AB  - Background: This study tested links between pubertal development and screen time
      among South Korean adolescent boys and girls. Methods: Secondary analysis was
      conducted on data from the Korean Children and Youth Panel Study (KCYPS)
      involving 2071 adolescents (age M = 13.14 years). Body mass index (BMI) at Grade
      8 (baseline), self-esteem and depression at Grade 9 were examined as mediators of
      the relationship between pubertal development and screen time after adjusting for
      household income and academic performance. Structural equation modeling was used
      to assess direct and indirect pathways between pubertal development at Grade 8
      and screen time at Grade 9. Results: No direct effect of pubertal development on
      screen time was found. But, an indirect effect existed for boys from pubertal
      development to screen time through BMI. Earlier pubertal development predicted
      higher BMI, and in turn, higher BMI predicted more time spent in screen time.
      Among girls, pubertal development negatively predicted BMI; however, no mediation
      effect of BMI between pubertal development and screen time was observed. No
      mediation effect of self-esteem or depression was found among boys or girls.
      Conclusions: Pubertal development appears to have an indirect influence on screen
      time through BMI for South Korean boys. More studies examining potential pathways
      between pubertal development and sedentary behavior are needed to build on these
      findings.

PMID- 29202068
TI  - Developing an approach to assessing the political feasibility of global
      collective action and an international agreement on antimicrobial resistance.
AB  - Background: Antimicrobial resistance (AMR) is a global issue. International
      trade, travel, agricultural practices, and environmental contamination all make
      it possible for resistant microbes to cross national borders. Global collective
      action is needed in the form of an international agreement or other mechanism
      that brings states together at the negotiation table and commits them to adopt or
      implement policies to limit the spread of resistant microorganisms. This article
      describes an approach to assessing whether political and stakeholder interests
      can align to commit to tackling AMR. Methods: Two dimensions affecting political
      feasibility were selected and compared across 82 countries: 1) states' global
      influence and 2) self-interest in addressing AMR. World Bank GDP ranking was used
      as a proxy for global influence, while human antibiotic consumption (10-year
      percent change) was used as a proxy for self-interest in addressing AMR. We used
      these data to outline a typology of four country archetypes, and discuss how
      these archetypes can be used to understand whether a proposed agreement may have
      sufficient support to be politically feasible. Results: Four types of countries
      exist within our proposed typology: 1) wealthy countries who have the expertise
      and financial resources to push for global collective action on AMR, 2) wealthy
      countries who need to act on AMR, 3) countries who require external assistance to
      act on AMR, and 4) neutral countries who may support action where applicable. Any
      international agreement will require substantial support from countries of the
      first type to lead global action, and from countries of the second type who have
      large increasing antimicrobial consumption levels. A large number of barriers
      exist that could derail efforts towards global collective action on AMR; issues
      of capacity, infrastructure, regulation, and stakeholder interests will need to
      be addressed in coordination with other actors to achieve an agreement on AMR.
      Conclusions: Achieving a global agreement on access, conservation, and innovation
      - the three pillars of AMR - will not be easy. However, smaller core groups of
      interested Initiator and Pivotal Countries could develop policy and resolve many
      issues. If highly influential countries take the lead, agreements could then be
      scaled up to achieve global action.

PMID- 29202069
TI  - The evolution of socioeconomic status-related inequalities in maternal health
      care utilization: evidence from Zimbabwe, 1994-2011.
AB  - Background: Inequalities in maternal health care are pervasive in the developing
      world, a fact that has led to questions about the extent of these disparities
      across socioeconomic groups. Despite a growing literature on maternal health
      across Sub-Saharan African countries, relatively little is known about the
      evolution of these inequalities over time for specific countries. This study
      sought to quantify and explain the observed differences in prenatal care use and
      professional delivery assistance in Zimbabwe. Methods: The empirical analysis
      uses four rounds of the nationwide Zimbabwe Demographic and Health Survey
      administered in 1994, 1999, 2005/06 and 2010/11. Two binary indicators were used
      as measures of maternal health care utilization; (1) the receipt of four or more
      antenatal care visits and (2) receiving professional delivery assistance for the
      most recent pregnancy. We measure inequalities in maternal health care use using
      the Erreygers corrected concentration index. A decomposition analysis was
      conducted to determine the underlying drivers of the measured disparities.
      Results: The computed concentration indices for professional delivery assistance
      and prenatal care reveal a mostly pro-rich distribution of inequalities between
      1994 and 2011. Particularly, the concentration index [95% confidence interval]
      for the receipt of prenatal care was 0.111 [0.056, 0.171] in 2005/06 and 0.094
      [0.057, 0.138] in 2010/11. For professional delivery assistance, the
      concentration index stood at 0.286 [0.244, 0.329] in 2005/06 and 0.324 [0.283,
      0.366] in 2010/11. The pro-rich inequality was also increasing in both rural and
      urban areas over time. The decomposition exercise revealed that wealth,
      education, religion and information access were the underlying drivers of the
      observed inequalities in maternal health care. Conclusions: In Zimbabwe,
      socioeconomic disparities in maternal health care use are mostly pro-rich and
      have widened over time regardless of the location of residence. Overall, we
      established that inequalities in wealth and education are amongst the top drivers
      of the observed disparities in maternal health care. These findings suggest that
      addressing inequalities in maternal health care utilization requires coordinated
      public policies targeting the more poor and vulnerable segments of the population
      in Zimbabwe.

PMID- 29202070
TI  - Identifying the poor for premium exemption: a critical step towards universal
      health coverage in Sub-Saharan Africa.
AB  - Premium exemption for the poor is a critical step towards achieving universal
      health coverage in sub-Saharan Africa due to the large proportion of the
      population living in extreme poverty who cannot pay premium. However, identifying
      the poor for premium exemption has been a big challenge for SSA countries. This
      paper is a succinct review of four methods available for identifying the poor,
      outlining the ideal conditions under which each of the methods should be used and
      the drawbacks associated with using each of the methods.

PMID- 29202071
TI  - Childhood anemia in Rural Haiti: the potential role of community health workers.
AB  - Background: Childhood iron deficiency anemia (IDA) is an important contributor to
      under-five mortality in the developing world. There is evidence that Community
      Health Worker (CHW) delivered programs to increase maternal knowledge of child
      health practices may decrease childhood IDA. This study reports findings on the
      association between a long standing CHW intervention and childhood anemia status
      in rural Haiti. Methods: Using structural equations and mediation analyses on
      data from a household-based survey of 621 mother/child dyads, we tested the
      hypothesis that CHW would have a direct positive effect on maternal knowledge and
      an indirect effect on childhood anemia in rural Haiti. Results: CHW contact was
      significantly associated with maternal knowledge of key child health practices
      (beta = 0.193, SE = 0.058, p = 0.001). However, knowledge was not associated with
      childhood anemia (beta = -0.008, SE = 0.009, p = 0.382). Maternal knowledge
      categories significantly affected by CHW contact included diarrheal prevention
      knowledge (beta = 0.111, SE = 0.045, p = 0.013) and signs of malnutrition (beta =
      0.217, SE = 0.071, p = 0.002). There was no significant association with
      knowledge of vitamin A and iron rich foods (beta = 0.057, SE = 0.032, p = 0.074),
      which is the intervention most likely to impact childhood anemia. In all path
      models tested, we identified the control variables low household socio-economic
      status, mothers' anemia status, and child's age less than 24 months as
      significant predictors of childhood anemia. Conclusions: CHWs delivered
      interventions are associated with improved maternal knowledge of child health
      practices in rural Haiti; however, this knowledge is not associated with improved
      childhood anemia. Concurrently with CHW-delivered programs, interventions
      household poverty are implied to impact childhood health outcomes in resource
      poor settings.

PMID- 29202072
TI  - Participatory approach to design social accountability interventions to improve
      maternal health services: a case study from the Democratic Republic of the Congo.
AB  - Background: Social accountability (SA) comprises a set of mechanisms aiming to,
      on the one hand, enable users to raise their concerns about the health services
      provided to them (voice), and to hold health providers (HPs) accountable for
      actions and decisions related to the health service provision. On the other hand,
      they aim to facilitate HPs to take into account users' needs and expectations in
      providing care. This article describes the development of a SA intervention that
      aims to improve health services responsiveness in two health zones in the
      Democratic Republic of the Congo. Methods: Beneficiaries including men, women,
      community health workers (CHWs), representatives of the health sector and local
      authorities were purposively selected and involved in an advisory process using
      the Dialogue Model in the two health zones: (1) Eight focus group discussions
      (FGDs) were organized separately during consultation aimed at sharing and
      discussing results from the situation analysis, and collecting suggestions for
      improvement, (2) Representatives of participants in previous FGDs were involved
      in dialogue meetings for prioritizing and integrating suggestions from FGDs, and
      (3) the integrated suggestions were discussed by research partners and set as
      intervention components. All the processes were audio-taped, transcribed and
      analysed using inductive content analysis. Results: Overall there were 121
      participants involved in the process, 51 were female. They provided 48
      suggestions. Their suggestions were integrated into six intervention components
      during dialogue meetings: (1) use CHWs and a health committee for collecting and
      transmitting community concerns about health services, (2) build the capacity of
      the community in terms of knowledge and information, (3) involve community
      leaders through dialogue meetings, (4) improve the attitude of HPs towards voice
      and the management of voice at health facility level, (5) involve the health
      service supervisors in community participation and; (6) use other existing
      interventions. These components were then articulated into three intervention
      components during programming to: create a formal voice system, introduce
      dialogue meetings improving enforceability and answerability, and enhance the
      health providers' responsiveness. Conclusions: The use of the Dialogue Model, a
      participatory process, allowed beneficiaries to be involved with other community
      stakeholders having different perspectives and types of knowledge in an advisory
      process and to articulate their suggestions on a combination of SA intervention
      components, specific for the two health zones contexts.

PMID- 29202073
TI  - What does the development of medical tourism in Barbados hold for health equity?
      an exploratory qualitative case study.
AB  - Background: Although the global growth of privatized health care services in the
      form of medical tourism appears to generate economic benefits, there is debate
      about medical tourism's impacts on health equity in countries that receive
      medical tourists. Studies of the processes of economic globalization in relation
      to social determinants of health suggest that medical tourism's impacts on health
      equity can be both direct and indirect. Barbados, a small Caribbean nation which
      has universal public health care, private sector health care and a strong tourism
      industry, is interested in developing an enhanced medical tourism sector. In
      order to appreciate Barbadians' understanding of how a medical tourism industry
      might impact health equity. Methods: We conducted 50 individual and small-group
      interviews in Barbados with stakeholders including government officials, business
      and health professionals. The interviews were coded and analyzed deductively
      using the schedule's questions, and inductively for novel findings, and discussed
      by the authors. Results: The findings suggest that in spite of Barbados'
      universal health care and strong population health indicators, there is expressed
      concern for medical tourism's impact on health equity. Informants pointed to the
      direct ways in which the domestic population might access more health care
      through medical tourism and how privately-provided medical tourism in Barbados
      could provide health benefits indirectly to the Barbadian populations. At the
      same time, they cautioned that these benefits may not materialize. For example,
      the transfer of public resources - health workers, money, infrastructure and
      equipment - to the private sector to support medical tourism with little to no
      return to government revenues could result in health inequity through reductions
      in access to and availability of health care for residents. Conclusions: In
      clarifying the direct and indirect pathways by which medical tourism can impact
      health equity, these findings have implications for health system stakeholders
      and decision-makers in Barbados and other countries attempting both to build a
      medical tourism industry and to protect health equity.

PMID- 29202074
TI  - Examining the changing health care seeking behavior in the era of health sector
      reforms in India: evidences from the National Sample Surveys 2004 & 2014.
AB  - Background: Health policy formulations in India have witnessed a shift from a
      reactive approach to a more proactive approach over the last decade. It is
      therefore important to understand the effectiveness of recent national health
      policies (such as the National Rural Health Mission and the National Urban Health
      Mission) in addressing the varied needs of the heterogeneous population of India.
      Methods: We use datasets from the National Sample Surveys carried out in 2004 and
      2014 to understand the change in the health seeking behavior as a result of these
      policies. The choice of health care facilities and the associated expenditures
      are compared through descriptive analyses. A multinomial logistic regression is
      used to identify the significant parameters which contribute towards the share of
      health care providers in India. The health status of two economically disparate
      Indian states (Bihar and Kerala) are also compared through specific metrics of
      performance. Results: It is seen that due to increased availability of facilities
      in close proximity, both rural and urban residents prefer to avail of those
      facilities which will result in minimization of transportation cost. The
      effectiveness of national health policies is found to vary on a regional scale.
      Literacy and health status have a strong correlation, thereby reinforcing that
      Bihar still lags far behind Kerala in terms of access to equitable health care.
      Conclusion: Therefore, a hierarchical system, incorporating medical pluralism and
      tailor-made policies targeted at diverse health care demands, needs to be put in
      place to achieve Goal 3 of the Sustainable Development Goals as decreed by the
      United Nations, i.e., "health for all".

PMID- 29202075
TI  - Aid effectiveness and programmatic effectiveness: a proposed framework for
      comparative evaluation of different aid interventions in a particular health
      system.
AB  - Background: Against a backdrop of changing concepts of aid effectiveness,
      development effectiveness, health systems strengthening, and increasing emphasis
      on impact evaluation, this article proposes a theory-driven impact evaluation
      framework to gauge the effect of aid effectiveness principles on programmatic
      outcomes of different aid funded programs in the health sector of a particular
      country. Methods: The foundation and step-by-step process of implementing the
      framework are described. Results: With empirical evidence from the field, the
      steps involve analysis of context, program designs, implementation mechanisms,
      outcomes, synthesis, and interpretation of findings through the programs'
      underlying program theories and interactions with the state context and health
      system. Conclusions: The framework can be useful for comparatively evaluating
      different aid interventions both in fragile and non-fragile state contexts.

PMID- 29202076
TI  - A globally networked hybrid approach to public health capacity training for
      maternal health professionals in low and middle income countries.
AB  - Background: MundoComm is a current NIH-funded project for sustainable public
      health capacity building in community engagement and technological advances aimed
      at improving maternal health issues. Two to four teams are selected annually,
      each consisting of three healthcare professionals and one technical person from
      specific low and middle income countries (LMICs) including Costa Rica, Dominican
      Republic, Honduras, and other LMICs. MundoComm is a course with three parts: in
      person workshops, online modules, and mentored community engagement development.
      Two annual 1-week on-site "short courses" convened in Costa Rica are supplemented
      with six monthly online training modules using the Moodle(r) online platform for
      e-learning, and mentored project development. The year-long course comprises over
      20 topics divided into the six modules - each module further segmented into 4
      week-long assignments, with readings and assigned tasks covering different
      aspects of community-engaged interventions. The content is peer reviewed by
      experts in the respective fields from University of Rochester, UCIMED in Costa
      Rica, and faculty from Costa Rica and the Dominican Republic who maintain regular
      contact with the trainees to mentor learning and project progress. The purpose of
      this paper is to report the first year results of the MundoComm project. Methods:
      Both quantitative and qualitative feedback (using online data capturing forms)
      assess baseline and post-training knowledge and skills in public health project
      strategies. Results: The course currently has one team each in Costa Rica, the
      Dominican Republic, and Honduras for a total of 12 trainees. The course and
      modules include best practices in information and communication technologies
      (ICTs), ethical reviews, community engagement, evidence-based community
      interventions, and e-Health strategies. To maximize successful and culturally
      appropriate training approaches, the multi-media didactic presentations, flexible
      distance learning strategies, and the use of tablets for offline data collection
      are offered to trainees, and then feedback from trainees and other lessons
      learned aid in the refinement of subsequent curricular improvements. Conclusions:
      Through remark and discussion, the authors report on 1) the feasibility of using
      a globally networked learning environment (GNLE) plus workshop approach to public
      health capacity training and 2) the capacity of LMIC teams to complete the
      MundoComm trainings and produce ICT-based interventions to address a maternal
      health issue in their respective regions.

PMID- 29202077
TI  - Eating practices during pregnancy: perceptions of select Maasai women in Northern
      Tanzania.
AB  - Background: Globally, pregnant women are challenged to meet sufficient and
      necessary dietary intake in order to improve maternal and neonatal outcomes.
      These challenges are amplified in traditional communities, such as the Maasai,
      where the historical and cultural practices may further curtail, or impact on
      this dyad's potential success. The research is intended to enhance understanding
      of Maasai women's pregnancy and nutrition traditions as well as their beliefs.
      Method: Interviews with 12 pregnant Maasai women, all originally from the
      (Ngorongoro Conservation Area Authority NCAA) area and have spent most or all of
      their adult lives in the NCAA, sought to answer two research questions: how do
      these women describe their current dietary pattern and what do they believe is
      the role of nutrition during pregnancy. Results: Interpretive description
      methodology was used to reveal five themes: (1) Eating less food makes baby come
      easier, (2) Not producing food means more dependence, (3) Working hard harms my
      baby, (4) Knowing what is needed for a good pregnancy and (5) Preferring our
      traditional ways for pregnancy and birth. Conclusions: There is an imperative to
      address nutrition throughout the perinatal period within the Maasai population
      and the women recognize how important nutrition is for them and their babies.
      Opportunities to incorporate cultural values and practices must be embedded in
      programmes/services to achieve success and sustainability. It is important for
      future prenatal programming with the Maasai in northern Tanzania and other
      vulnerable groups of pregnant women to build on the women's knowledge of what
      leads to good pregnancy outcomes.

PMID- 29202078
TI  - Global climate change: impact of heat waves under different definitions on daily
      mortality in Wuhan, China.
AB  - Background: There was no consistent definition for heat wave worldwide, while a
      limited number of studies have compared the mortality effect of heat wave as
      defined differently. This paper aimed to provide epidemiological evidence for
      policy makers to determine the most appropriate definition for local heat wave
      warning systems. Methods: We developed 45 heat wave definitions (HWs) combining
      temperature indicators and temperature thresholds with durations. We then
      assessed the impact of heat waves under various definitions on non-accidental
      mortality in hot season (May-September) in Wuhan, China during 2003-2010.
      Results: Heat waves defined by HW14 (daily mean temperature >= 99.0th percentile
      and duration >= 3 days) had the best predictive ability in assessing the
      mortality effects of heat wave with the relative risk of 1.63 (95% CI: 1.43,
      1.89) for total mortality. The group-specific mortality risk using official heat
      wave definition of Chinese Meteorological Administration was much smaller than
      that using HW14. We also found that women, and the elderly (age >= 65) were more
      susceptible to heat wave effects which were stronger and longer lasting.
      Conclusion: These findings suggest that region specific heat wave definitions are
      crucial and necessary for developing efficient local heat warning systems and for
      providing evidence for policy makers to protect the vulnerable population.

PMID- 29202079
TI  - Increasing protocol suitability for clinical trials in sub-Saharan Africa: a
      mixed methods study.
AB  - Background: The trial protocol is the most important document for clinical trials
      and describes not only the design and methodology of a study, but also all
      practical aspects. The suitability of the protocol has a direct impact on the
      execution and results of the trial. However, suitability is rarely addressed in
      trial practice and research. The aim of our study was to investigate protocol
      suitability and to identify suitability-enhancing measures for trials in sub
      Saharan Africa. Methods: We used an exploratory mixed methods design. First, we
      interviewed 36 trial staff at different organisational levels in Ghana, Burkina
      Faso and Senegal. Second, we conducted an online survey among trial staff in sub
      Saharan Africa to investigate trial protocol suitability based on the main themes
      distilled from the interviews. Results: Protocol suitability surfaced as a
      prominent topic in interviews with trial staff, critiqued for its lack of
      clarity, implementability and adaptation to trial participants as well as to the
      workforce and infrastructure available. Both qualitative and quantitative
      investigations identified local site staff involvement in protocol development as
      the most helpful mean of increasing protocol suitability. Careful assessment of
      the local context, capacity and cultures, and ensuring that staff understand the
      protocol were also cited as helpful measures. Conclusions: Our data suggests that
      protocol suitability can be increased by discussing and reviewing the protocol
      with trial staff in advance. Involving operationally experienced staff would be
      most useful. For multicentre trials, we suggest that at least one trial staff
      member from each of the sites with the highest expected recruitment rates be
      involved in developing the protocol. Carefully assessing the context prior to
      study start is indispensable to ensuring protocol suitability and should
      particularly focus on the workforce and infrastructure available, as well as the
      needs and availability of trial participants. To allow for protocol suitability
      enhancing measures, planners must allocate enough time for trial preparation and
      solicit feedback and information on context at an early stage. Such prospective
      planning would increase implementability, efficiency and quality of trials in the
      long run.

PMID- 29202080
TI  - A practical approach for scaling up the alternative strategy for the elimination
      of lymphatic filariasis in Loa loa endemic countries - developing an action plan.
AB  - Background: Lymphatic filariasis (LF) is a vector-borne parasitic disease that is
      being targeted for elimination through mass drug administration (MDA). The co
      distribution of Loa loa in Central Africa poses a significant barrier to the
      expansion of the MDA due to risk of severe adverse events (SAEs) associated with
      the drug ivermectin that is routinely used. National LF programmes are yet to
      significantly scale up in co-endemic areas and need a practical approach to make
      preliminary decisions based on the mapping status and potential treatment
      strategies. Methods: We reviewed relevant data available to WHO and in the
      literature for LF-L. loa endemic countries to develop a simple method to support
      the scale-up of MDA to eliminate LF. Results: A basic model for national LF
      programmes to work from at the administrative or implementation unit (IU) level
      has been developed for LF - L. loa co-endemic countries. The model includes five
      practical steps, which comprise the development of a national filarial database
      and a simple classification system to help determine the mapping status and most
      appropriate treatment strategy. Steps are colour-coded and linked to a general
      decision tree, which is also presented. Conclusions: This IU-level model is
      simple to follow and will help LF elimination programmes develop an action plan
      and scale up the implementation of alternative treatment strategies in L. loa co
      endemic areas. The model could be further developed to incorporate the additional
      complexity of IUs where an intervention is required to eliminate onchocerciasis,
      particularly in hypo-endemic areas where ivermectin has not been used.

PMID- 29202082
TI  - Assessment of the availability and rationality of unregistered fixed dose drug
      combinations in Nepal: a multicenter cross-sectional study.
AB  - Background: The medications that are registered and available in a country are
      meant for the prevention and treatment of ailments and diseases. However, a lack
      of effective regulatory bodies and operative control mechanisms, especially in
      developing countries, promotes irrational and inappropriate use of medicines.
      This study aims to evaluate the availability and rationality of unregistered
      fixed-dose drug combinations (FDCs) in Nepal. Methods: A snowball sampling method
      with visits to 20 retail pharmacies in each of five major cities in Nepal was
      used to assess the availability of unregistered FDCs. To justify the rationality
      of the FDCs obtained from these five cities, the toolkit developed by Health
      Action International Asia-Pacific (HAI-AP) was used. Results: Altogether, 41
      unregistered FDCs were obtained from the five cities. Among the total 41 FDCs, a
      majority were anti-inflammatory/analgesic/antipyretics. A maximum of eight drugs
      and a minimum of two drugs per combination were present among the total 41 FDCs,
      with a majority in the form of tablets followed by suspensions. The cost ranges
      from a minimum of 3.7 Nepalese Rupees (NRs) (= USD 0.05) to a maximum of 240 NRs
      (= USD 3.15). None of the FDCs fulfilled all the fundamental requirements as
      stated in the toolkit; thus, they were categorized as 'irrational'. Conclusions:
      Unregistered FDCs are available in the Nepalese pharmaceutical market. All the
      unregistered FDCs found in our study were 'irrational' as per the HAI-AP toolkit.
      Regulatory authorities should initiate strict monitoring and appropriate
      regulatory mechanisms to prohibit the use of unregistered and irrational FDCs.

PMID- 29202081
TI  - Phylodynamic applications in 21st century global infectious disease research.
AB  - Background: Phylodynamics, the study of the interaction between epidemiological
      and pathogen evolutionary processes within and among populations, was originally
      defined in the context of rapidly evolving viruses and used to characterize
      transmission dynamics. The concept of phylodynamics has evolved since the early
      21st century, extending its reach to slower-evolving pathogens, including
      bacteria and fungi, and to the identification of influential factors in disease
      spread and pathogen population dynamics. Results: The phylodynamic approach has
      now become a fundamental building block for the development of comparative
      phylogenetic tools capable of incorporating epidemiological surveillance data
      with molecular sequences into a single statistical framework. These innovative
      tools have greatly enhanced scientific investigations of the temporal and
      geographical origins, evolutionary history, and ecological risk factors
      associated with the growth and spread of viruses such as human immunodeficiency
      virus (HIV), Zika, and dengue and bacteria such as Methicillin-resistant
      Staphylococcus aureus. Conclusions: Capitalizing on an extensive review of the
      literature, we discuss the evolution of the field of infectious disease
      epidemiology and recent accomplishments, highlighting the advancements in
      phylodynamics, as well as the challenges and limitations currently facing
      researchers studying emerging pathogen epidemics across the globe.

PMID- 29202083
TI  - Escaping from poverty trap: a choice between government transfer payments and
      public services.
AB  - Background: Anti-poverty has always been an important issue to be settled. What
      policies should be selected to help individuals escaping from the poverty trap:
      by directly offering transfer payments or indirectly providing public services?
      This paper is among the first to explore the effects of public anti-poverty
      programs system in China. Methods: We Using unbalanced panel data of China Health
      and Nutrition Survey (CHNS) from 1989 to 2009, we demonstrate how the individual
      poverty status is determined through a four-staged simultaneous model. We choose
      the 3SLS (Three Staged Linear Squared) methodology to do the estimation. Results:
      GTPs (Government Transfer Payments) don't have positive effects on poverty
      reductions. The results demonstrate that GTPs increasing by 10% makes private
      transfer payments decrease by 3.9%. Meanwhile, GTPs increasing by 10% makes the
      household income decreased by 27.1%. However, public services (such as medical
      insurance, health services, hygiene protection etc.) have significantly positive
      impacts on poverty reduction. Public services share a part of living cost of the
      poor, and are conducive for people to gain higher household income. Conclusions:
      GTPs given by governments are not effective in reducing the poverty, as a result
      of "crowd-out effect" and "inductive effect". However, public services are
      suggested to be adopted by governments to help the poor out of the poverty trap.

PMID- 29202084
TI  - The market for reproductive tourism: an analysis with special reference to
      Greece.
AB  - Background: For many people, the need for parenthood remains unfulfilled due to
      biological reasons and a remedy for these individuals is assisted reproduction
      (AR). Because of widely differing and sometimes incompatible legislations around
      the world related to AR, there is considerable confusion across national borders.
      Within Europe, Greece seems to be in a comparatively favorable position because
      of lower restrictions and the availability of decent quality specialized medical
      facilities. This research is a market study with a business perspective and
      explores the emerging landscape of reproductive tourism (RT) in Greece. Methods:
      The research adopted mixed methods. First, open-ended questions were used to
      interview foreign medical tourists and staff in various AR clinics. Based on the
      insights from these interviews and guided by the extent literature, a survey
      instrument was prepared and administered among 130 patients. Results: Findings
      indicate that Greece still lack policies that nurture transparency and dynamic
      response to technological changes in AR. Also, the travel industry lack
      specialists who can effectively liaison with clinics, who understand the
      availability of AR technologies, regulations, and the unique needs of AR
      tourists. Conclusions: Globally, the need for assisted reproduction has
      tremendously increased; yet, the supply of facilities is lagging far behind.
      There is a unique advantage for clinics located in touristic locations in
      countries that offer cheaper treatment options. Given the shape of its debt
      ridden economy, Greece needs foreign exchange inflows and gaining first mover
      advantage in reproductive tourism is probably an important way to achieve this.
      This research draws up a reproductive tourism strategy for Greece.

PMID- 29202085
TI  - Body weight misperception and psychological distress among young South Korean
      adults: the role of physical activity.
AB  - Background: Emerging evidence suggests that body weight misperception may be
      associated with psychological distress among people in developed countries.
      Participating in physical activity (PA) may negate the association between weight
      misperception and psychological distress given the well-known benefits of PA on
      psychological health. This study examined the role of PA in associations between
      body weight misperception and psychological distress among young South Korean
      adults. Methods: Data from individuals aged 20 to 39 years who participated in
      the Fifth Korean National Health and Nutrition Examination Surveys 2010-2012 (N =
      6055) was included in the logistic regressions. Results: The proportions of the
      respondents under- and over-perceiving their body weight were 66.9% and 0.8%
      among men and 16.3% and 15.6% among women respectively. A moderating effect of PA
      participation was observed on the relationship between body weight over
      perception and depressed mood (Odds Ratio [OR] = 0.55; 95% Confidence Intervals
      [95% CI] = 0.34, 0.89). Among individuals who did not meet the recommended
      vigorous-intensity PA (>= 20 min/session and >= 3 day/week), body weight over
      perception was associated with depressed mood (OR = 1.71, 95% CI = 1.19, 2.46)
      compared to the accurate-perception group. However, no association was observed
      among those who met the recommended vigorous-intensity PA (OR = 1.52, 95% CI =
      0.45, 5.22). Similar patterns were found among physically active versus inactive
      individuals (recommended walking not met: OR = 2.02, 95% CI = 1.29, 3.15;
      recommended walking met: OR = 1.28, 95% CI = 0.66, 2.49; muscular strengthening
      exercises for < 2 day/week: OR = 1.74, 95% CI = 1.21, 2.51; muscular
      strengthening exercises for >= 2 day/week: OR = 1.38, 95% CI = 0.37, 5.14). No
      relationship existed between body weight over-perception and depressed mood after
      adjusting for PA. Conclusions: Participating in regular PA may buffer a potential
      negative impact of body weight over-perception on depressive mood.

PMID- 29202086
TI  - Strategies and governance to reduce health inequalities: evidences from a cross
      European survey.
AB  - Background: The main objective of the paper is to identify the governance system
      related to policies to reduce health inequalities in the European regions.
      Considering the Action Spectrum of inequalities and the check list of health
      equity governance, we developed a survey in the framework of the AIR Project -
      Addressing Inequalities Intervention in Regions - was an European project funded
      by the Executive Agency of Health and Consumers. Methods: A web-based qualitative
      questionnaire was developed that collected information about practiced strategies
      to reduce health inequalities. In total 28 questionnaires from 28 different
      regions, related to 13countries, were suitable for the analysis. Results:
      Progress in health equity strategies at the national and regional levels has been
      made by countries such as France, Portugal, Poland, and Germany. On the other
      hand, Spain, Italy, and Belgium have a variable situation depending on the
      region. However, the results of the survey indicate that the governance system
      for health equity different in terms of commitment, resources and tools.
      Conclusions: The survey highlights a weakness of governance system for the
      majority of countries in terms of evaluation actions and of impact of
      interventions in reducing inequalities, and the difficulties in having a clear
      and integrated vision between the national and regional levels.

PMID- 29202087
TI  - Factors influencing the tobacco control policy process in Egypt and Iran: a
      scoping review.
AB  - Introduction: Tobacco control policy is essential for addressing the growing
      tobacco consumption seen in the Eastern Mediterranean Region, the single greatest
      preventable contributor to the non-communicable disease epidemic. Egypt and Iran
      have had varied success in using policy to combat this issue. The study aims to
      identify and compare the factors which have influenced different stages of the
      policy process - evidence generation, development and implementation. Methods: A
      scoping review was conducted with a systematic search of 7 databases which was
      conducted along with searches of Google Scholar, and the World Health
      Organisation and Eastern Mediterranean Regional Office websites to identify
      influencing factors at each stage of the policy process. Results: Twenty-seven
      relevant articles were identified from the literature search. Factors identified
      as influencing tobacco control policy in these countries were lobbying by the
      tobacco industry, the rise of water-pipe smoking, lack of political commitment
      and the lack of resources to for policy implementation. Iran was found to be
      leading Egypt on all three areas of the policy process. Implementation was found
      to be the most pivotal part of the policy process and the area in which Egypt was
      weakest compared to Iran. Conclusion: This study addresses a gap in knowledge
      concerning tobacco control in the Middle East and has identified multiple factors
      which are potentially slowing the process of enforcing policy to address tobacco
      consumption. Iran is the regional leader for tobacco control and it is important
      for Egypt to assess the transferability of its tactics and immediately start
      implementing measures to control tobacco use.

PMID- 29202089
TI  - The role of risk perception in willingness to respond to the 2014-2016 West
      African Ebola outbreak: a qualitative study of international health care workers.
AB  - Background: The 2014-2016 West Africa Ebola Virus Disease (EVD) outbreak was an
      unprecedented public health event, and in addition to claiming over 11,000 lives,
      it resulted in the deaths of more healthcare workers than any outbreak in recent
      history. While a cadre of willing and able health workers is essential for an
      effective epidemic response, health workforce capacity in times of crisis may be
      significantly impacted by how risks are perceived by health staff. This study
      aimed to explore how risk perceptions influenced healthcare workers' willingness
      to respond during this outbreak. Methods: Through in-depth interviews with 11
      front-line international health care workers who chose to respond to the West
      Africa outbreak, this qualitative study explores how perceptions of risk
      developed and subsequently mediated the decision to respond to the outbreak. Data
      was thematically organized using NVivo 10. Results: We found that numerous
      individual and social-level factors played a role in modifying risk perception in
      health workers. Institutional trust emerged as a key risk attenuator, as did past
      experience, self-efficacy, duty of care, humanitarian ethos, and cognitive
      heuristics. Feelings of risk were amplified by infections of co-workers, and risk
      perceptions of family members and the public, which were mainly informed by media
      reports, also hampered willingness to respond in some cases. Conclusions:
      Understanding the risk perceptions of health workers, institutions, and the
      public, while complex and interdependent, are each crucial to understand for an
      effective public health response to epidemics, and as such should be taken into
      consideration in future program planning and research.

PMID- 29202088
TI  - "If we are waiting for the numbers alone, we will miss the point": a qualitative
      study of the perceived rise of food allergy and associated risk factors in the
      Greater Accra Region, Ghana.
AB  - Background: Globally, food allergy [FA] is considered a growing health epidemic.
      While much of what is known comes from developed countries, there is growing
      interest in the epidemiology of FA in developing regions such as sub-Saharan
      Africa. Indeed, researchers are beginning to document the incidence and
      prevalence of FA and sensitization. The results outlined in this paper stem from
      an exploratory qualitative study examining the emergence of the health risk of FA
      in Ghana, a country undergoing epidemiologic changes. Methods: Between June and
      August, 2015, we conducted thirty-seven (37) semi-structured in-depth interviews.
      This comprised seventeen (17) healthcare workers across 12 public and private
      hospitals and twenty (20) individuals with FA and families with allergic
      children. All interviews were recorded and transcribed verbatim. Transcripts were
      analyzed to develop thematic areas that characterize perceptions and experiences
      around FA. Results: Three key broad themes arise from this study. First, FA is an
      emerging health risk, whose incidence is perceived to be increasing. Second,
      participants expressed mixed perceptions about the public health burden of FA.
      Third, participants identified individual and societal factors that may be
      influencing FA risks and susceptibility. Conclusion: Our research suggests FA is
      a growing but unrecognized public health concern. There is the need for health
      policies and researchers to consider the full extent of ongoing epidemiologic
      changes for the health of populations in developing regions.

PMID- 29202090
TI  - Joint spatial modelling of disease risk using multiple sources: an application on
      HIV prevalence from antenatal sentinel and demographic and health surveys in
      Namibia.
AB  - Background: In disease mapping field, researchers often encounter data from
      multiple sources. Such data are fraught with challenges such as lack of a
      representative sample, often incomplete and most of which may have measurement
      errors, and may be spatially and temporally misaligned. This paper presents a
      joint model in the effort to deal with the sampling bias and misalignment.
      Methods: A joint (bivariate) spatial model was applied to estimate HIV prevalence
      using two sources: 2014 National HIV Sentinel survey (NHSS) among pregnant women
      aged 15-49 years attending antenatal care (ANC) and the 2013 Namibia Demographic
      and Health Surveys (NDHS). Results: Findings revealed that health districts and
      constituencies in the northern part of Namibia were found to be highly associated
      with HIV infection. Also, the study showed that place of residence, gender,
      gravida, marital status, number of kids dead, wealth index, education, and condom
      use were significantly associated with HIV infection in Namibia. Conclusion: This
      study had shown determinants of HIV infection in Namibia and had revealed areas
      at high risk through HIV prevalence mapping. Moreover, a joint modelling approach
      was used in order to deal with spatially misaligned data. Finally, it was shown
      that prediction of HIV prevalence using the NDHS data source can be enhanced by
      jointly modelling other HIV data such as NHSS data. These findings would help
      Namibia to tailor national intervention strategies for specific regions and
      groups of population.

PMID- 29202092
TI  - China's engagement with development assistance for health in Africa.
AB  - Background: As an emerging donor in health related development across the world,
      particularly towards Africa, the People's Republic of China (PRC) has been
      increasing its influence within the field of global public health over the past
      few decades. Yet between the period of 2000 and 2013, little is known about the
      scope, scale and priority of China's grant-making programs. Methods: Based on
      data sourced from the China Aid Database (version-1.2), descriptive analyses were
      applied to analyze the features of 531 health related projects that were
      undertaken between 2000 and 2013. Spearmen correlation was also performed to
      assess the relationship between China's export and aid to recipient countries.
      Results: The total value of China's grant-making programs in the health related
      sector between 2000 and 2013 was 5.67 billion USD, with 531 projects undertaken.
      During the five year period between 2004 and 2008, China had a contribution of
      1.54 billion USD, which increased to 3.8 billion USD during the five year period
      between 2009 and 2013 - an 146.26% increase. In terms of specific diseases, China
      is most concerned with building an African public health system through donations
      targeted towards general health (313 projects), combating Malaria (115 projects)
      and maternal, neonatal and child health (MNCH), (12 projects). When it comes to
      recipient countries, if counted in total value, Zimbabwe received the most
      financial assistance from China, totaling 1.08 billion USD and 19 projects, while
      Angola and Tanzania received more projects - 30 and 29 projects respectively. In
      terms of the channeling of aid funding, most projects were targeted towards
      infrastructure, equipment and medicine (304 projects in total), followed by
      medical teams (189 projects). Moreover, there is a statistically significant
      relationship between aid to Africa and Chinese exports to Africa. Conclusion:
      During the past decade, Chinese aid projects played an important role in the
      African public health system through providing funding for infrastructure,
      equipment and medicine, training health professionals, as well as disease
      treatment. However, very limited attention was paid towards disease prevention,
      health promotion and awareness initiatives, and health education. Furthermore,
      serious questions were raised regarding the long-term financial sustainability
      and actual impact these projects have on health development.

PMID- 29202091
TI  - Health financing policies in Sub-Saharan Africa: government ownership or donors'
      influence? A scoping review of policymaking processes.
AB  - Background: The rise on the international scene of advocacy for universal health
      coverage (UHC) was accompanied by the promotion of a variety of health financing
      policies. Major donors presented health insurance, user fee exemption, and
      results-based financing policies as relevant instruments for achieving UHC in Sub
      Saharan Africa. The "donor-driven" push for policies aiming at UHC raises
      concerns about governments' effective buy-in of such policies. Because the latter
      has implications on the success of such policies, we searched for evidence of
      government ownership of the policymaking process. Methods: We conducted a scoping
      review of the English and French literature from January 2001 to December 2015 on
      government ownership of decision-making on policies aiming at UHC in Sub-Saharan
      Africa. Thirty-five (35) results were retrieved. We extracted, synthesized and
      analyzed data in order to provide insights on ownership at five stages of the
      policymaking process: emergence, formulation, funding, implementation, and
      evaluation. Results: The majority of articles (24/35) showed mixed results (i.e.
      ownership was identified at one or more levels of policymaking process but not
      all) in terms of government ownership. Authors of only five papers provided
      evidence of ownership at all reviewed policymaking stages. When results
      demonstrated some lack of government ownership at any of the five stages, we
      noticed that donors did not necessarily play a role: other actors' involvement
      was contributing to undermining government-owned decision-making, such as the
      private sector. We also found evidence that both government ownership and donors'
      influence can successfully coexist. Discussion: Future research should look
      beyond indicators of government ownership, by analyzing historical factors behind
      the imbalance of power between the different actors during policy negotiations.
      There is a need to investigate how some national actors become policy champions
      and thereby influence policy formulation. In order to effectively achieve
      government ownership of financing policies aiming at UHC, we recommend
      strengthening the State's coordination and domestic funding mobilization roles,
      together with securing a higher involvement of governmental (both political and
      technical) actors by donors.

PMID- 29202093
TI  - Health status and health systems financing in the MENA region: roadmap to
      universal health coverage.
AB  - Background: Since the declaration of the Millennium Development Goals (MDGs) in
      1990, many countries of the Middle East and North Africa (MENA) region made some
      improvements in maternal and child health and in tackling communicable diseases.
      The transition to the global agenda of Sustainable Development Goals brings new
      opportunities for countries to move forward toward achieving progress for better
      health, well-being, and universal health coverage. This study provides a profile
      of health status and health financing approaches in the MENA region and their
      implications on universal health coverage. Methods: Time-series data on
      socioeconomics, health expenditures, and health outcomes were extracted from
      databases and reports of the World Health Organization, the World Bank and the
      United Nations Development Program and analyzed using Stata 12 statistical
      software. Countries were grouped according to the World Bank income categories.
      Descriptive statistics, tables and charts were used to analyze temporal changes
      and compare the key variables with global averages. Results: Non-communicable
      diseases (NCDs) and injuries account for more than three quarters of the
      disability-adjusted life years in all but two lower middle-income countries
      (Sudan and Yemen). Prevalence of risk factors (raised blood glucose, raised blood
      pressure, obesity and smoking) is higher than global averages and counterparts by
      income group. Total health expenditure (THE) per capita in most of the countries
      falls short of global averages for countries under similar income category.
      Furthermore, growth rate of THE per capita has not kept pace with the growth rate
      of GDP per capita. Out-of-pocket spending (OOPS) in all but the high-income
      countries in the group exceeds the threshold for catastrophic spending implying
      that there is a high risk of households getting poorer as a result of paying for
      health care. Conclusion: The alarmingly high prevalence of NCDs and injuries and
      associated risk factors, health spending falling short of the GDP and GDP growth
      rate, and high OOPS pose serious challenges for universal health coverage. Using
      multi-sector interventions, countries should develop and implement evidence
      informed health system financing roadmaps to address these obstacles and move
      forward toward universal health coverage.

PMID- 29202094
TI  - The 'experimental public' in longitudinal health research: views of local leaders
      and service providers in rural South Africa.
AB  - Background: The concept of 'experimental public' has been recently applied to
      publics involved in clinical trials. This term could also be applied to publics
      involved in longitudinal research such as health and demographic surveillance
      systems. The ethics of practice and public engagement with these experimental
      publics are of key importance and include issues of informed consent,
      confidentiality, collection of body tissue samples and fair local benefit.
      Methods: Individual (n = 11) and focus group (n = 5) qualitative semi-structured
      interviews were conducted with 56 local leaders and service providers regarding
      their views about research activities in a longitudinal health research study
      site run by the MRC/Wits Rural Public Health and Health Transitions Research Unit
      (Agincourt) in rural South Africa. Deductive and inductive thematic analysis was
      undertaken using NVivo software to identify the emergent themes. Results: There
      was an understanding of the usefulness of collecting demographic data, but
      reasons for gathering other contextual data such as on food security, as well as
      the reasons for collection of blood was less clear. While appreciation was
      expressed for feedback of individual results such as blood pressure levels during
      home-based data collection, there were requests for more results from biomarkers,
      and for these to be given at home, rather than at the clinic. There were reports
      of indirect refusals, and offers by leaders to assist in reducing refusal rates.
      There were concerns about confidentiality, especially in the publication of
      results. Some leaders would have liked to receive more individual level data for
      planning of services, although they understood this would breach confidentiality.
      Service providers were concerned about the withdrawal of some services post
      intervention trials. Conclusions: This experimental public has, over time,
      developed a nuanced understanding of the reasons for research and the procedures
      undertaken. Discussions concerning fair benefit ranged from requests for more
      individual clinically-relevant results for participants, to understanding how
      research results could assist in planning of public health services at local and
      national levels. The concerns illustrate the complexity of the ethics of practice
      which has implications for policy, practice and governance for those working in
      longitudinal health research sites globally.

PMID- 29202095
TI  - Anal sexual experience and HIV risk awareness among female sex workers in Dire
      Dawa, eastern Ethiopia.
AB  - Background: Female sex workers have been disproportionately affected with HIV and
      anal sexual experience elevate their vulnerability. Anal intercourse has more
      risk of HIV transmission than vaginal intercourse for receptors that coupled with
      low condom and proper lubricant use behavior during anal sex. Besides majority of
      them did not understand HIV transmission risk of anal intercourse. In Ethiopia,
      studies on anal sexual experience is almost none existent, so the purpose of this
      study is to explored anal sexual experience and HIV transmission risk awareness
      among female sex worker in Dire Dawa, Eastern Ethiopia. Method: Qualitative study
      with thematic analysis approach was conducted among 18 female sex workers and
      recruitment of study participants performed until saturation of information. The
      principal investigator conducted in-depth interviews using local language
      (Amharic) and it was recorded on audio recorder. Tape recorded data was
      transcribed and translated to English and entered into open code version 3.4 for
      coding and theme identification. Data collection conducted simultaneously with
      data analysis. Result: Female sex workers practiced anal sex for different themes
      like financial influence, coercion, intentionally, peer pressure and as a sign of
      intimacy and love. Coercion, negative attitudes, poor awareness about HIV
      transmission risks of anal sex and protection capacity of condom and proper
      lubricants are the identified themes for not using condom and proper lubricants
      during anal sex by female sex workers. Inaccessibility and unavailability of
      health services for issues related to anal sex was the core reason for female sex
      workers' misperception and risk anal sexual experience. Conclusion: Female sex
      workers practiced anal sex without risk reduction approaches and they did not
      understand exacerbated risk of anal sex to HIV transmission. Stakeholders
      including ministry of health need to incorporate potential awareness raising
      tasks and programs about risk of anal sex and methods of risk reduction for
      female sex workers.

PMID- 29202096
TI  - Trafficking of Vietnamese women and girls for marriage in China.
AB  - Background: Bride-trafficking has been a growing phenomenon in Southeast Asia,
      particularly in China, where one-child policies have resulted in demographic
      imbalances favoring males. Yet, empirical evidence about women and girls sold
      into marriage in China remains sparse. Methods: This study describes the
      experiences of 51 Vietnamese women and girls as young as 14 in post-trafficking
      services who were sold into marriage in China. A consecutive sample of
      individuals from five services in Vietnam were invited to be interviewed within
      the first 2 weeks of admission. It is part of a wider dataset for research on the
      health of men, women, and children in post-trafficking services in Cambodia,
      Thailand, and Vietnam, the largest study to date on human trafficking and health.
      We calculated proportions for all variables and conducted bivariate analyses
      using Fisher Exact Tests for their associations with mental health disorders
      symptoms. Results: Before leaving home, 31% (n = 15) participants were married.
      Participants reported high levels of sexual violence (n = 43; 86%) while
      trafficked and59% (n = 30) spent time in detention before returning to Vietnam.
      Once in post-trafficking care 52.9% (n = 27) reported probable depression,
      anxiety or post-traumatic stress disorders (PTSD), two women (4%) attempted
      suicide in the past month and 38 (75%) remained afraid of their trafficker. Ten
      (22%) became pregnant while trafficked, and seven (16%) were pregnant at the
      interview. Conclusions: The cross-border bride trade between Vietnam and China
      raises complex policy issues, including questions about detention and immigration
      rights and strategies for supported return processes, including maternal and
      child health services. As the repercussions of China's absent female population
      will persist, Vietnam and China must grapple with the political and social
      conditions to implement prevention strategies, and resources for women who fall
      prey to this cross-border bride trade.

PMID- 29202097
TI  - Targeted community based interventions improved malaria management competencies
      in rural Ghana.
AB  - Background: Malaria is one of the most challenging public health concerns in the
      developing world. To address its impact in endemic regions, several interventions
      are implemented by stakeholders. The Affordable Medicine Facility-malaria (AMFm)
      is an example of such interventions. Its activities include communication
      interventions to enhance the knowledge of caregivers of children under five
      years, licensed chemical sellers (LCS) and prescribers on malaria management with
      artemisinin-based combination therapy (ACT). This study was conducted to evaluate
      the effectiveness of the AMFm activities on malaria among targeted groups in two
      rural communities in Ghana. Methods: A communication intervention study was
      conducted in the Asante-Akim North and South Districts of Ghana. Repeated cross
      sectional pre and post surveys were deployed. Relevant malaria messages were
      designed and used to develop the information, education and communication (IEC)
      tools for the intervention. With the aid of posters and flipcharts developed by
      our study, community health workers (CHWs), prescribers, and licenced chemical
      sellers provided proper counselling to clients on malaria management. Trained
      CHWs and community based volunteers educated caregivers of children under five
      years on malaria management at their homes and at public gatherings such as
      churches, mosques, schools. Chi-square tests and logistic regression were run to
      determine associations and control for demographic differences respectively.
      Results: There was significantly high exposure to malaria/ACT interventions in
      the intervention district than in the comparison district (OR = 16.02; 95% CI =
      7.88-32.55) and same for malaria/ACT-related knowledge (OR = 3.63; 95% CI = 2.52
      5.23). The participants in the intervention district were also more knowledgeable
      about correct administration of dispersible drug for children <5 years than their
      counterparts in the unexposed district. Conclusion: Our data show that targeted
      interventions improve malaria based competences in rural community settings. The
      availability of subsidized ACTs and the intensity of the communication campaigns
      contributed to the AMFm-related awareness, improved knowledge on malaria/ACTs and
      management practices.

PMID- 29202098
TI  - Qatar steps up to Global Health security: a reflection on the joint external
      evaluation, 2016.
AB  - Since the commencement of the International Health Regulations in 2007, global
      public health security has been faced with numerous emerging and ongoing events.
      Moreover, the Joint External Evaluation is a voluntary tool developed in
      compliance with the Global Health Security Agenda that represents the high
      responsibility of international health community towards the increased incidence
      of emerging and re-emerging diseases. Against this background, between 29th May
      and 2nd June 2016, a team of World Health Organization consultants arrived to the
      State of Qatar to assess, in collaboration with national experts, the country's
      capacity to prevent, detect, and rapidly respond to threats of public health
      aspect. They identified areas of strength, weakness, and recommendations for
      improving national health security of Qatar in anticipation of the 2022 FIFA
      World Cup event. Qatar has demonstrated a leading role in the region through its
      commitment to International Health Regulations (2005) and population health.
      Similarly, the Qatar was the first Arab state and seventh volunteering country
      globally to undergo the Joint External evaluation process. In this review, we
      highlighted Qatar's achievements and shortcomings of International Health
      Regulations' core capacities to inform healthcare professionals and the
      scientific community about the country's contribution toward global health
      security.

PMID- 29202099
TI  - Predictors and consequences of rural clients' satisfaction level in the district
      public-private mixed health system of Bangladesh.
AB  - Background: We investigated predictors of the rural clients' satisfaction level
      (CSL), and interlinks between perceived specific service quality (PSSQ),
      perceived utility value (PUV), CSL, and clients' reactions (CR) towards current
      and future utilization of providers and facilities in the public-private mixed
      health system of Bangladesh. Methods: A quantitative study using interviewer
      administered questionnaire was conducted among 400 rural patients. CSL was
      measured both directly and indirectly. Clients' opinions of PSSQ relating to
      healthcare structure and process features were measured for indirectly assessing
      their satisfaction. PUV and CR were also measured indirectly. 5-point Likert
      scales were used to measure PSSQ, PUV, CSL and CR. Multiple regression and
      mediation were the models. Results: Clients' satisfaction was low in both health
      sectors with significantly lower in the public than private sector. Accessibility
      (financial) predicted commonly high variations in CSL both in the public (18.2%)
      and private sectors (25.0%). Availability predicted incomparably highest
      variations in CSL in the public sector (34.6%). Structural factors predicted
      higher variations in clients' satisfaction in the public sector, which in the
      private sector were service process-features. Clients' reaction was the ultimate
      outcome of PSSQ mediated through PUV and CSL. PUV mediated the effects of PSSQ on
      clients' reaction stronger than CSL. Conclusion: Financial accessibility is a
      crucial risk of impoverishment in both public and private sectors. Both
      structural and process features of healthcare are in ample needs for addressing
      existing low satisfaction in patients in rural Bangladesh.

PMID- 29202100
TI  - Immediate assessment of performance of medical laboratory scientists following a
      10-day malaria microscopy training programme in Nigeria.
AB  - Background: Rapid and precise diagnosis of malaria is an essential element in
      effective case management and control of malaria. Malaria microscopy is used as
      the gold standard for malaria diagnosis, however results remain poor as
      positivity rate in Nigeria is consistently over 90%. The United States
      President's Malaria Initiative (PMI) through the Malaria Action Program for
      States (MAPS) supported selected states in Nigeria to build capacity for malaria
      microscopy. This study demonstrates the effectiveness of in-service training on
      malaria microscopy amongst medical laboratory scientists. Method: The training
      was based on the World Health Organization (WHO) basic microscopy training
      manual. The 10-day training utilized a series of didactic lectures and
      examination of teaching slides using a CX 21 Olympus binocular microscope. All
      108 medical laboratory scientists trained from 2012 to 2015 across five states in
      Nigeria supported by PMI were included in the study. Evaluation of the training
      using a pre-and post-test method was based on written test questions; reading
      photographic slide images of malaria parasites; and prepared slides. Result:
      There was a significant improvement in the mean written pre-and post-tests scores
      from 37.9% (95% CI 36.2-39.6%) to 70.7% (95% CI 68.4-73.1%) (p < 0.001). The mean
      counting post-test score improved significantly from 4.2% (95% CI 2.6-5.7%) to
      27.9% (95% CI 25.3-30.5%) (p < 0.001). Mean post-test score for computer-based
      picture speciation test (63.0%) and picture detection test (89.2%) were
      significantly higher than the mean post-test score for slide reading speciation
      test (38.3%) and slide reading detection test (70.7%), p < 0.001 in both cases.
      Conclusion: Parasite detection and speciation using enhanced visual imaging was
      significantly improved compared with using direct microscopy. Regular in-service
      training and provision of functional and high resolution microscopes are needed
      to ensure quality routine malaria microscopy.

PMID- 29202101
TI  - Review on the prevalence of diabetes and risk factors and situation of disease
      management in floating population in China.
AB  - Objective: To give a comprehensive and basic understanding of diabetes and its
      risk factors in floating people in China. Method: We use "(diabetes or type 2
      diabetes or chronic disease) and (floating population or employed floating
      population)" as the key words to search in the China academic literature database
      (CNKI), Wan Fang database, PubMed and Web of Science for relevant literature and
      extract the data about the prevalence of diabetes, relevant risk factors and
      disease management of the floating population in China. Result: Twenty-one
      literatures are entered into analysis finally, one is English and the rest are
      Chinese. According to the national survey, the prevalence rate of diabetes in
      floating population in China was 5. 1% (95%CI, 4.9% - 5.3%), which is lower than
      that of the general population(11.6%,95%CI, 11.3%-11.8%),and is consistent with
      the results of the local surveys. The comparison result between the prevalence of
      floating population and that of local population in each region differs in local
      surveys. In addition, the prevalence of male floating population is lower than
      that of the female population. Finally, as the age of the population rises, so
      does the prevalence of diabetes. As for the risk factors of chronical diseases,
      the overweight rate in every region is similar but the obesity rate differs in
      different regions (Ningxia,26.0%;Xiangshan,14.0%), and the obesity rate of the
      floating population is less than half of that of the general people(4.7%,11.9%).
      The awareness rate, treatment rate and control rate in the floating patients
      differ in the regional researches, but they all can't meet the goals set by the
      local health departments. Conclusion: Compared with the general population, the
      prevalence of diabetes in the floating population are lower. However, Considering
      the growing population number and the poor disease management of the floating
      patients, the potential threat brought by the diabetes in floating population is
      imponderable. The government should establish the national surveillance system of
      diabetes for the floating population, strengthen the construction of the primary
      medical institutions, and optimize the existing funding system.

PMID- 29202102
TI  - Combinatorial treatment with natural compounds in prostate cancer inhibits
      prostate tumor growth and leads to key modulations of cancer cell metabolism.
AB  - High-throughput screening of a natural compound library was performed to identify
      the most efficacious combinatorial treatment on prostate cancer. Ursolic acid,
      curcumin and resveratrol were selected for further analyses and administered in
      vivo via the diet, either alone or in combination, in a mouse allograft model of
      prostate cancer. All possible combinations of these natural compounds produced
      synergistic effects on tumor size and weight, as predicted in the screens. A
      subsequent untargeted metabolomics and metabolic flux analysis using isotopically
      labeled glutamine indicated that the compound combinations modulated glutamine
      metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were
      modulated to a greater extent by the combinations compared to the individual
      compounds. Overall, this approach can be useful for identifying synergistic
      combinations of natural compounds for chemopreventive and therapeutic
      interventions.

PMID- 29202103
TI  - Early changes in glioblastoma metabolism measured by MR spectroscopic imaging
      during combination of anti-angiogenic cediranib and chemoradiation therapy are
      associated with survival.
AB  - Precise assessment of treatment response in glioblastoma during combined anti
      angiogenic and chemoradiation remains a challenge. In particular, early detection
      of treatment response by standard anatomical imaging is confounded by pseudo
      response or pseudo-progression. Metabolic changes may be more specific for tumor
      physiology and less confounded by changes in blood-brain barrier permeability. We
      hypothesize that metabolic changes probed by magnetic resonance spectroscopic
      imaging can stratify patient response early during combination therapy. We
      performed a prospective longitudinal imaging study in newly diagnosed
      glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular
      endothelial growth factor receptor inhibitor cediranib in combination with
      standard fractionated radiation and temozolomide (chemoradiation). Forty patients
      were imaged weekly during therapy with an imaging protocol that included magnetic
      resonance spectroscopic imaging, perfusion magnetic resonance imaging, and
      anatomical magnetic resonance imaging. Data were analyzed using receiver operator
      characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots.
      We observed that the ratio of total choline to healthy creatine after 1 month of
      treatment was significantly associated with overall survival, and provided as
      single parameter: (1) the largest area under curve (0.859) in receiver operator
      characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox
      proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan
      Meier survival plots. An inverse correlation was observed between total
      choline/healthy creatine and cerebral blood flow, but no significant relation to
      tumor volumetrics was identified. Our results suggest that in vivo metabolic
      biomarkers obtained by magnetic resonance spectroscopic imaging may be an early
      indicator of response to anti-angiogenic therapy combined with standard
      chemoradiation in newly diagnosed glioblastoma.

PMID- 29202104
TI  - A Health Profile of Senior-Aged Women Veterans: A Latent Class Analysis of
      Condition Clusters.
AB  - Background and Objectives: This study characterizes the multiple morbidities
      experienced by senior-aged women Veterans so that the Veterans Health
      Administration (VHA) and other healthcare systems may be better prepared to meet
      the healthcare needs of this growing cohort. Research Design and Methods: Using
      the VHA's Corporate Data Warehouse (CDW), we conducted a retrospective
      observational study of the 38,597 female veteran patients who were at least sixty
      five years old and received care in the VHA during 2013 and 2014. We use a latent
      class analysis model to cluster diagnoses associated with inpatient and
      outpatient events over the years. Results: The senior-aged women Veterans are
      characterized by six major classes of disease clusters. We defined these classes
      as: Healthy (16.24% of the cohort); Ophthalmological Disorders (13.84%);
      Musculoskeletal Disorders (14.22%); At Risk for Cardiovascular Disease (37.53%);
      Diabetic with Comorbidities (9.05%); and Multimorbid (9.12%). The patterns and
      prevalence of these condition classes vary by race, age and marital status.
      Discussion and Implications: Each of the six clusters can be used to develop
      clinical practice guidelines that are appropriate for senior-aged women Veterans.
      Consistent with past literature, the most common conditions in this cohort are
      hypertension and hyperlipidemia; together they form the most common class, "At
      Risk of Cardiovascular Disease (CVD)". Results also show evidence of race-related
      disparities, with Blacks being more likely to be in the highest risk classes.
      Also, members of the cohort who are currently married having improved chances of
      being in the healthy class. And finally, we see a "healthy survivor" effect with
      the oldest women in our cohort having low overall rates of disease.

PMID- 29202105
TI  - Biophotonic markers of malignancy: Discriminating cancers using wavelength
      specific biophotons.
AB  - Early detection is a critically important factor when successfully diagnosing and
      treating cancer. Whereas contemporary molecular techniques are capable of
      identifying biomarkers associated with cancer, surgical interventions are
      required to biopsy tissue. The common imaging alternative, positron-emission
      tomography (PET), involves the use of nuclear material which poses some risks.
      Novel, non-invasive techniques to assess the degree to which tissues express
      malignant properties are now needed. Recent developments in biophoton research
      have made it possible to discriminate cancerous cells from normal cells both in
      vitro and in vivo. The current study expands upon a growing body of literature
      where we classified and characterized malignant and non-malignant cell types
      according to their biophotonic activity. Using wavelength-exclusion filters, we
      demonstrate that ratios between infrared and ultraviolet photon emissions
      differentiate cancer and non-cancer cell types. Further, we identified photon
      sources associated with three filters (420-nm, 620-nm., and 950-nm) which
      classified cancer and non-cancer cell types. The temporal increases in biophoton
      emission within these wavelength bandwidths is shown to be coupled with
      intrisitic biomolecular events using Cosic's resonant recognition model.
      Together, the findings suggest that the use of wavelength-exclusion filters in
      biophotonic measurement can be employed to detect cancer in vitro.

PMID- 29202106
TI  - Proposing a new stroke-specific screening tool for depression: Examination of
      construct validity and reliability.
AB  - Objectives: The optimal tool for identifying depression after stroke is yet to be
      identified. In the present study, we propose a new context-specific screening
      tool for PSD and examined its construct validity and reliability within existing
      data on recent stroke survivors. Methods: We assessed baseline data being
      collected as part of an intervention to improve one-year blood pressure control
      among recent (<=one month) stroke survivors. Depression was measured using the
      Hospital Anxiety and Depression Scale (HADS-D). We also independently
      administered the 26-items Health Related Quality of Life in Stroke Patients
      (HRQOLISP-26), a stroke-specific measure developed from a large cross-cultural
      sample. Using standard protocol, we identified 6 psychoemotional-domain items of
      the HRQOLISP-26 fitting a single dimensional model with phenomenological and
      conceptual overlap with the depression framework in the 10th revision of the
      International Classification of Diseases (ICD-10). We examined construct validity
      by comparing HRQOLISP-E with the HADS-D, and known group validity by comparing
      with age, gender, and stroke severity using both the Pearson product moment
      coefficient and multivariate regression analyses. Internal consistency and split
      half reliability were also determined. Results: Each HRQOLISP-E item (r = -0.40
      to -0.53, all p < 0.001), as well as the total HRQOLISP-E score (-0.53, p <
      0.001) showed significant correlation with the HADS-D. The HRQOLISP-E scores also
      correlated significantly with age and stroke severity. Depression assessed using
      the HRQOLIPS-E was independently associated with older age and stroke severity.
      All HRQOLISP-E items scale correlations were> 0.8 (0.81-0.93) compared with 0.56
      0.68 for the HADS-D (Cronbach's alpha =0.939, versus 0.742 for the HADS-D, Split
      half reliability = 0.899, versus 0.739 for HADS-D). Conclusion: These results
      provides preliminary support for further development of the HRQOLISP-E as a
      context-specific screening tool for PSD through an investigation comparing the
      proposed measure against a referent-standard clinical diagnostic criteria such as
      the ICD 10 or Diagnostic and Statistical Manual of Fourth Edition of the
      Diagnostic and Statistical Manual of Mental Disorders.

PMID- 29202107
TI  - A multi-level spatial analysis of clinical malaria and subclinical Plasmodium
      infections in Pailin Province, Cambodia.
AB  - Background: The malaria burden is decreasing throughout the Greater Mekong
      Subregion, however transmission persists in some areas. Human movement,
      subclinical infections and complicated transmission patterns contribute to the
      persistence of malaria. This research describes the micro-geographical
      epidemiology of both clinical malaria and subclinical Plasmodium infections in
      three villages in Western Cambodia. Methods: Three villages in Western Cambodia
      were selected for the study based on high reported Plasmodium falciparum
      incidence. A census was conducted at the beginning of the study, including
      demographic information and travel history. The total population was 1766. Cross
      sectional surveys were conducted every three months from June 2013 to June 2014.
      Plasmodium infections were detected using an ultra-sensitive, high-volume,
      quantitative polymerase chain reaction (uPCR) technique. Clinical episodes were
      recorded by village health workers. The geographic coordinates (latitude and
      longitude) were collected for all houses and all participants were linked to
      their respective houses using a demographic surveillance system. Written informed
      consent was obtained from all participants. Results: Most clinical episodes and
      subclinical infections occurred within a single study village. Clinical
      Plasmodium vivax episodes clustered spatially in each village but only lasted for
      a month. In one study village subclinical infections clustered in geographic
      proximity to clusters of clinical episodes. The largest risk factor for clinical
      P. falciparum episodes was living in a house where another clinical P. falciparum
      episode occurred (model adjusted odds ratio (AOR): 6.9; CI: 2.3-19. 8).
      Subclinical infections of both P. vivax and P. falciparum were associated with
      clinical episodes of the same species (AOR: 5.8; CI: 1.5-19.7 for P. falciparum
      and AOR: 14.6; CI: 8.6-25.2 for P. vivax) and self-reported overnight visits to
      forested areas (AOR = 3.8; CI: 1.8-7. 7 for P. falciparum and AOR = 2.9; CI: 1.7
      4.8 for P. vivax). Discussion: Spatial clustering within the villages was
      transient, making the prediction of spatial clusters difficult. Interventions
      that are dependent on predicting spatial clusters (such as reactive case
      detection) would only have detected a small proportion of cases unless the entire
      village was screened within a limited time frame and with a highly sensitive
      diagnostic test. Subclinical infections may be acquired outside of the village
      (particularly in forested areas) and may play an important role in transmission.

PMID- 29202108
TI  - KRAS biomarker testing disparities in colorectal cancer patients in New Mexico.
AB  - Introduction: American Society of Clinical Oncology (ASCO) guidelines recommend
      that all patients with metastatic colorectal cancer (mCRC) receive KRAS testing
      to guide anti-EGFR monoclonal antibody treatment. The aim of this study was to
      assess for disparities in KRAS testing and mutational status. Methods: The New
      Mexico Tumor Registry (NMTR), a population-based cancer registry participating in
      the National Cancer Institute's Surveillance, Epidemiology and End Results
      program, was queried to identify all incident cases of CRC diagnosed among New
      Mexico residents from 2010 to 2013. Results: Six hundred thirty-seven patients
      were diagnosed with mCRC from 2010-2013. As expected, KRAS testing in Stage 4
      patients presented the highest frequency (38.4%), though testing in stage 3
      (8.5%), stage 2 (3.4%) and stage 1 (1.2%) was also observed. In those with
      metastatic disease, younger patients (<= 64 years) were more likely to have had
      testing than patients 65 years and older (p < 0.0001). Patients residing in urban
      areas received KRAS testing more often than patients living in rural areas (p =
      0.019). No significant racial/ethnic disparities were observed (p = 0.66). No
      significant differences were seen by year of testing. Conclusion: Age and
      geographic disparities exist in the rates of KRAS testing, while sex,
      race/ethnicity and the year tested were not significantly associated with
      testing. Further study is required to assess the reasons for these disparities
      and continued suboptimal adherence to current ASCO KRAS testing guidelines.

PMID- 29202109
TI  - ylmD and ylmE genes are dispensable for growth, cross-wall formation and
      sporulation in Streptomyces venezuelae.
AB  - Streptomycetes are Gram-positive filamentous soil bacteria that grow by tip
      extension and branching, forming a network of multinucleoid hyphae. These
      bacteria also have an elaborate process of morphological differentiation, which
      involves the formation of an aerial mycelium that eventually undergoes extensive
      septation into chains of uninucleoid cells that further metamorphose into spores.
      The tubulin-like FtsZ protein is essential for this septation process. Most of
      the conserved cell division genes (including ftsZ) have been inactivated in
      Streptomyces without the anticipated lethality, based on studies of many other
      bacteria. However, there are still some genes of the Streptomyces division and
      cell wall (dcw) cluster that remain uncharacterized, the most notable example
      being the two conserved genes immediately adjacent to ftsZ (i.e. ylmDE). Here,
      for the first time, we made a ylmDE mutant in Streptomyces venezuelae and
      analysed it using epifluorescence microscopy, scanning electron microscopy (SEM)
      and atomic force microscopy (AFM). The mutant showed no significant effects on
      growth, cross-wall formation and sporulation in comparison to the wild type
      strain, which suggests that the ylmDE genes do not have an essential role in the
      Streptomyces cell division cycle (at least under the conditions of this study).

PMID- 29202110
TI  - Aberrant Temporal Connectivity in Persons at Clinical High Risk for Psychosis.
AB  - Background: Schizophrenia, a neurodevelopmental disorder, involves abnormalities
      in functional connectivity (FC) across distributed neural networks, which are
      thought to antedate the emergence of psychosis. In a cohort of adolescents and
      young adults at clinical high risk (CHR) for psychosis, we applied data-driven
      approaches to resting-state fMRI data so as to systematically characterize FC
      abnormalities during this period and determine whether these abnormalities are
      associated with psychosis risk and severity of psychotic symptoms. Methods: Fifty
      one CHR participants and 47 matched healthy controls (HCs) were included in our
      analyses. Twelve of these CHR participants developed psychosis within 3.9 years.
      We estimated one multivariate measure of FC and studied its relationship to CHR
      status, conversion to psychosis and positive symptom severity. Results:
      Multivariate analyses revealed between-group differences in whole-brain
      connectivity patterns of bilateral temporal areas, mostly affecting their
      functional connections to the thalamus. Further, more severe positive symptoms
      were associated with greater connectivity abnormalities in the anterior cingulate
      and frontal cortex. Conclusions: Our study demonstrates that the well-established
      FC abnormalities of the thalamus and temporal areas observed in schizophrenia are
      also present in the CHR period, with aberrant connectivity of the temporal cortex
      most associated with psychosis risk.

PMID- 29202111
TI  - The role of natural processes and surface energy of inhaled engineered
      nanoparticles on aggregation and corona formation.
AB  - The surface chemistry of engineered nanoparticles (ENPs) becomes more important
      as their size decreases and enters the nanometer-range. This review explains the
      fundamental properties of the surface chemistry of nanoparticles, and argues that
      their agglomeration and the formation of corona around them are natural processes
      that reduce surface energy. ENP agglomeration and surface corona formation are
      further discussed in the context of inhaled ENPs, as the lung is a major port of
      ENP entry to the body. The pulmonary surfactant layer, which the inhaled ENPs
      first encounter as they land on the lung surface, represents a unique environment
      with a variety of well-defined biomolecules. Many factors, such as
      hydrophobicity, surface charge of ENPs, protein/phospholipid concentrations of
      the alveolar lining fluid, etc. influence the complex processes of ENP
      agglomeration and corona formation in the alveolar lining fluid, and these events
      occur even before the ENPs reach the cells. We suggest that molecular dynamic
      simulations can represent a promising future direction for research of the
      behavior of inhaled ENPs, complementing the experimental approaches. Moreover, we
      want to remind biologists working on ENPs of the importance relationship between
      ENP surface energy and size.

PMID- 29202113
TI  - Ten Years HIV Free: An Interview with "The Berlin Patient," Timothy Ray Brown.

PMID- 29202112
TI  - Epigenetic effects of environmental chemicals: insights from zebrafish.
AB  - Zebrafish have been extensively used for studying vertebrate development and
      modeling human diseases such as cancer. In the last two decades, they have also
      emerged as an important model for developmental toxicology research and, more
      recently, for studying the developmental origins of health and disease (DOHaD).
      It is widely recognized that epigenetic mechanisms mediate the persistent effects
      of exposure to chemicals during sensitive windows of development. There is
      considerable interest in understanding the epigenetic mechanisms associated with
      DOHaD using zebrafish as a model system. This review summarizes our current
      knowledge on the effects of environmental chemicals on DNA methylation, histone
      modifications and noncoding RNAs in the context of DOHaD, and suggest some key
      considerations in designing experiments for characterizating the mechanisms of
      action.

PMID- 29202114
TI  - Dihydrosanguinarine Enhances Glucose Uptake in Mouse 3T3-L1 Cells.
AB  - Recently, more studies have aimed at identifying selective peroxisome
      proliferator-activated receptor gamma (PPARgamma) modulators that transactivate
      the expression of PPARgamma-dependent genes as partial agonists to improve
      diabetic symptoms with fewer side effects compared to classic PPARgamma agonists
      such as thiazolidinediones. We found that dihydrosanguinarine (DHS) treatment
      induced preadipocyte differentiation and lipid droplet accumulation in 3T3-L1
      cells, but this effect is weaker than that elicited by the full PPARgamma agonist
      troglitazone. Furthermore, this effect was reduced by the addition of a PPARgamma
      antagonist, indicating the involvement of PPARgamma signaling. Our results
      suggest that the stimulatory effects of DHS on adipocyte differentiation and
      insulin sensitivity are mediated by suppressing adenosine monophosphate-activated
      protein kinase (AMPK) alpha, upregulating the expression of PPARgamma and its
      target genes (particularly Glut-4 and adiponectin) and reducing PPARgamma
      phosphorylation. DHS significantly enhanced the glucose uptake in 3T3-L1
      adipocytes without observable cytotoxicity at the effective concentration (5 MUM)
      applied.

PMID- 29202115
TI  - Rapid changes in peripheral lymphocyte concentrations during interferon-free
      treatment of chronic hepatitis C virus infection.
AB  - : Treatment of chronic hepatitis C virus infection with direct acting antivirals
      results in a rapid decline in viral load and markers of hepatic inflammation,
      including serum CXCL10 concentration, which is followed in most cases by a
      sustained virologic response. Whether parallel changes of significance occur in
      the cellular composition of peripheral blood is relatively unknown. We
      hypothesized that longitudinal characterization of peripheral blood during
      treatment would provide insight into cellular migration and immune activation,
      which would have implications for understanding host immunity both before and
      after HCV treatment and may relate to HCV clearance. We analyzed longitudinal
      peripheral innate and adaptive immune cell populations by flow cytometry from 95
      subjects enrolled in two direct acting antiviral clinical trials, and examined
      chemokine receptor expression on T-lymphocytes in 43 patients. Within 1-2 weeks
      of initiating treatment, significant increases were observed in the concentration
      of peripheral CD4+ and CD8+ T-lymphocytes, but not monocyte or natural killer
      cells. In tandem with these changes, the percent of both CD4+ and CD8+ T
      lymphocytes with an activated phenotype (HLA-DR+ and CD38+) decreased, and T
      lymphocyte surface expression of CXCR3, the chemokine receptor for CXCL10,
      increased. Conclusion: Rapid changes in peripheral cellular populations occur
      during DAA -treatment of HCV infection, which could potentially relate to hepatic
      efflux of tissue lymphocytes due to altered inflammation and chemokine receptor
      signaling, providing critical insight into the relationship between host immunity
      and viral clearance during hepatitis C virus infection.

PMID- 29202117
TI  - Association between intimate partner violence and mentally unhealthy days in
      women in the U.S.
AB  - Background: In the United States (U.S.), intimate partner violence (IPV) is a
      serious public health concern, mainly affecting the health and well-being of
      women. The objective of this study was to identify the IPV and socio-demographic
      factors associated with mentally unhealthy days among women in the U.S. of ages
      >=18 years. Methods: Data for this study were obtained from the 2007 Behavioral
      Risk Factor Surveillance System. Multivariable analyses were used to estimate
      adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs) for factors
      associated with IPV and 14 or more mentally unhealthy days per month. Analyses
      were conducted using SAS 9.3. Results: The analyses show that the following
      factors increase the likelihood of self-reported 14 or more mentally unhealthy
      days: having a high school level of education or less (AOR: 1.732; 95% CI: 1.415
      2.119) and having an income < $50,000. In addition, experiencing IPV such as:
      ever being threatened by a sex partner (AOR: 1.499; 95% CI: 1.264-1.779); having
      a sex partner ever attempt violence (AOR: 1.461; 95% CI: 1.224-1.743); having a
      sex partner ever become violent (AOR: 1.541; 95% CI: 1.303-1.823); and ever
      having unwanted sex with a partner (AOR: 1.929; 95% CI: 1.584-2.350) also
      increased the likelihood of self-reported 14 or more mentally unhealthy days per
      month. Conclusions: The results indicate that, for women in the U.S., IPV and
      socio-demographic factors have an effect on self-reported 14 or more mentally
      unhealthy days. Improving access to services that offer protection and guidance
      for women abused by their intimate partner could decrease the likelihood of
      selfreported 14 or more mentally unhealthy days and long-term negative mental
      health outcomes among women.

PMID- 29202118
TI  - Emergency Department Asthma Medication Delivery Program: An Initiative to Provide
      Discharge Prescriptions and Education.
AB  - Background: Prescription fill rates for children being discharged from the
      emergency department (ED) after asthma exacerbations are low, placing the child
      at risk for additional ED visits or admissions for asthma. This article describes
      the implementation of an ED asthma prescription delivery service designed to
      improve pharmacy prescription capture and decrease ED revisit rates. Methods: A
      core group developed a service to provide asthma prescriptions and education to
      patients in their ED room before discharge. The project assessed the percent of
      ED asthma patients who filled ED asthma prescriptions at the hospital outpatient
      pharmacy, 7-, 14-, and 30-day ED revisit rates, and patient satisfaction.
      Intervention: Patients/families who chose to participate in the service received
      asthma prescriptions and education at the ED bedside. Within 1-3 days, ED
      outreach nurses obtained patient satisfaction survey responses via telephone.
      Results: There was a statistically significant increase in the number of patients
      who filled ED asthma prescriptions at the hospital outpatient pharmacy (22.2%
      versus 33.8%; P < 0.0001). The decrease in 7-, 14-, or 30-day ED revisit rates
      for patients who received the medication delivery service compared with standard
      of care was not statistically significant. Patients were satisfied to very
      satisfied with the service. Conclusion: Postimplementation of a medication
      delivery program within the ED, there was an increase in the percentage of
      patients who filled ED asthma medication prescriptions at the hospital outpatient
      pharmacy. There was no difference in ED revisit rates for patients who enrolled
      in the prescription delivery service versus standard of care.

PMID- 29202116
TI  - Developmental corticosterone treatment does not program immune responses in zebra
      finches (Taeniopygia guttata).
AB  - Developmental conditions may impact the expression of immune traits throughout an
      individual's life. Early-life challenges may lead to immunological constraints
      that are mediated by endocrine-immune interactions. In particular, individual
      differences in the ability to mount immune responses may be programmed by
      exposure to stressors or glucocorticoid hormones during development. To test this
      hypothesis, we experimentally elevated levels of the glucocorticoid hormone
      corticosterone during the nestling and fledgling periods in captive zebra finches
      (Taeniopygia guttata). We subsequently challenged birds with the antigen
      lipopolysaccharide (LPS) on days 60 and 100 post-hatch to determine if
      developmental exposure to elevated corticosterone impacted the later response to
      LPS. As measures of immune function, we quantified bacteria killing ability,
      haptoglobin concentrations, and LPS-specific antibody responses at multiple time
      points. We also measured circulating corticosterone concentrations during the
      experimental period and on day 60 before and after endotoxin challenge. During
      the experimental period, corticosterone treatment elevated corticosterone levels.
      Corticosterone treatment did not induce programming effects on immune function or
      corticosterone production. Independent of treatment, individuals with higher
      corticosterone concentrations during the nestling period had lower bacteria
      killing ability on day 36 and higher baseline corticosterone concentrations on
      day 60 post-hatch. These results suggest a limited role for corticosterone
      exposure during early life to mediate immunological constraints later in life.
      Manipulation of cortisol may be necessary to conclusively determine if
      developmental glucocorticoid exposure can program immune function in birds. To
      determine if developmental stress can program the immune response, exposure to
      environmentally relevant stressors should also be manipulated.

PMID- 29202119
TI  - Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe
      Demyelinating Diseases.
AB  - Background: Our group has used deep sequencing to identify viral RNA signatures
      in human brain specimens. We have previously used this method to detect HSV1, GBV
      C, and measles virus sequence in brain tissue from deceased donors. Deep
      sequencing was performed on brain specimens from a cohort of patients who died
      with progressive forms of MS, revealing evidence of increased expression of some
      human endogenous retrovirus (HERV) domains. Objectives: Identify RNA sequences
      and new antigens involved in the pathogenesis of MS. Methods: Deep sequencing was
      performed on RNA extracted from 12 progressive MS, 2 neuromyelitis optica (MS/NMO
      = demyelination group), 14 normal control, and 7 other neurologic disease (OND)
      control frozen brain specimens. The resulting single-ended 50 bp sequences
      (reads) were compared to a non redundant viral database representing (NRVDB) all
      1.2 M viral records in GenBank. A retroviral gene catalog (RVGC) was prepared by
      identifying human genetic loci (GRCh37.p13) homologous to domains contained in
      the Gypsy 2.0 retro element database. Reads were aligned to the RVGC and human
      transcriptome with Bowtie2. The resulting viral hit rates (VHRs) were normalized
      by the number of high quality reads. The expression of human genes, including
      HERVs, was determined using Cufflinks. Comparisons between the groups were
      performed using the false discovery rate. Results: Fifty to 131 million high
      quality reads per specimen were obtained. Comparison of the reads to the NRVDB
      suggested that the demyelination and OND specimens had higher VHRs against some
      retroviral sequences compared with the controls. This was confirmed by retroviral
      domain averaging. Gene expression analysis showed differential expression among
      some HERV sequences. Single read mapping revealed one envelope and one reverse
      transcriptase sequence record that were significantly enriched among the
      demyelination samples compared to the normal controls. Less restrictive
      (comprehensive) read mapping showed that 2 integrase, 2 core, 2 envelope, and 3
      KRAB sequences that were overexpressed in the demyelination group. Conclusions:
      These data demonstrate that some endogenous retroviral sequences are
      significantly overexpressed in these demyelination brain tissue specimens, but
      the magnitude of this overexpression is small. This is consistent with the
      concept of HERV activation as a part of the innate immune response.

PMID- 29202120
TI  - Health Literacy Universal Precautions Are Still a Distant Dream: Analysis of U.S.
      Data on Health Literate Practices.
AB  - Background: Experts have recommended the adoption of health literacy universal
      precautions, whereby health care providers make all health information easier to
      understand, confirm everyone's comprehension, and reduce the difficulty of health
      related tasks. The U.S. Department of Health and Human Services selected three
      health literate practices to track progress in the adoption of health literacy
      universal precautions. Objectives: This study sought to examine whether there has
      been an increase in the delivery of health literate care and whether
      recommendations for health literacy universal precautions are being followed.
      Methods: This study used trend and multiple regression analyses of data from 2011
      to 2014 from the Medical Expenditure Panel Survey, a national household survey.
      Key Results: The proportion of adults in the U.S. who reported receiving health
      literate care increased from 2011 to 2014, but fell far short of health literacy
      universal precautions recommendations of delivering health literate care to
      everyone. In 2014, 70% of the population reported their providers always gave
      them instructions that were easy to understand, but only 29% were asked to Teach
      Back the instructions and only 17% were offered help with forms. Older, less
      educated, and racial and ethnic minority group members were more likely to report
      receiving health literate care than more advantaged groups. People who perceived
      their health and mental health as fair or poor were less likely to report
      receiving health literate care. Conclusions: Failure to adopt health literacy
      universal precautions in the face of the high prevalence of limited health
      literacy in the general population may perpetuate adverse health outcomes that
      are costly to society. Greater efforts should be made to increase providers'
      health literacy skills, particularly those who serve populations that are more
      likely to have limited health literacy, including those with poor health. Plain
      Language Summary: This study shows that some health care providers did not always
      check that their instructions were clear enough for patients to understand. Even
      fewer providers always offered help in filling out forms. People who were older,
      less educated, or members of racial or ethnic minority groups were more likely to
      be asked to confirm their understanding or be offered help with forms. More
      patients said that their provider was easy to understand, checked their
      understanding, or offered help with forms in 2014 than in 2011.

PMID- 29202121
TI  - Low level of the plasma sphingolipid, glucosylceramide, is associated with
      thrombotic diseases.
AB  - Background: One previous pilot study suggested the association of low plasma
      glucosylceramide (GlcCer) levels with venous thrombosis (VTE) risk. Objective: We
      aimed to confirm and evaluate the association of low plasma GlcCer levels with
      VTE and myocardial infarction (MI) occurrence, respectively. Patients and
      Methods: We evaluated the association of GlcCer in two independent case-control
      studies of Caucasian VTE populations (N = 210 and 636) and one case-control study
      of Caucasian MI patients (N = 345). Result: Plasma GlcCer levels in VTE patients
      were lower compared to controls in two independent VTE populations (5.0 vs 5.8
      MUg/mL, p = 0.003 for the Scripps registry, and 5.6 vs 6.0 MUg/mL, p = 0.001 for
      the Valencia registry, respectively). A low plasma GlcCer level (below 10th
      percentile of controls) was associated with increased VTE occurrence [odds ratio
      (OR) = 3.7 (95%CI, 1.8-7.9) for Scripps registry and OR = 2.1 (95%CI, 1.3-3.3)
      for Valencia registry, respectively). For the MI study, the median GlcCer plasma
      level was lower in MI patients than in controls (4.3 vs 5.6 MUg/mL, p<0.001), and
      a low level of GlcCer (below 10th percentile of control) was associated with
      higher MI occurrence [OR = 7.7, (95%CI, 4.3-13.8)]. Conclusion: Lower
      concentration of GlcCer was associated with VTE occurrence in two independent
      studies and also with MI occurrence in one study.

PMID- 29202123
TI  - Modern contraceptive methods utilization and associated factors among
      reproductive aged women in rural Dembia District, northwest Ethiopia: Community
      based cross-sectional study.
AB  - Background: Improving women's health through modern contraceptive methods
      utilization is the key strategy to prevent unwanted pregnancy and its
      complication. However, there was limited evidence on utilization of modern
      contraceptive methods in the study area. Objective: This study identified factors
      affecting utilization of modern contraceptive methods among women at reproductive
      age group in rural areas of Dembia district, 2015. Materials and Methods:
      Community based cross sectional study was conducted in 2015 in Dembia District.
      Multi-stage sampling technique was used to select a total of 616 study
      participants. Bivariate and multivariable logistic regression model was fitted to
      identify factors associated with modern contraceptive utilization. Odds ratio
      with 95% confidence interval (CI) was computed to determine the level of
      significance. Results: Modern contraceptive methods utilization was found to be
      31.7% 95%CI (28.0-35.3). Age [Adjusted odds ratio (AOR): 1.94, (95%CI: 1.170
      3.216)], women who has educated husband [AOR: 0.28, (95%CI: 0.117-0.666)],
      Marital status [AOR: 2.81, (95%CI: 1.344-5.855)] and Spousal announcement about
      family planning issues [AOR: 2.58, (95%CI: (1.276-5.202)] were factors associated
      with modern contraceptive methods utilization. Conclusion: Modern contraceptive
      methods utilization was found to be low. Providing educational opportunities,
      creating awareness about contraception and effective counseling would increase
      modern contraceptive methods utilization.

PMID- 29202122
TI  - Evaluation of vitamin D status and its correlation with oxidative stress markers
      in women with polycystic ovary syndrome.
AB  - Background: There is little evidence about antioxidant properties of vitamin D.
      Recent studies suggest that oxidative stress may play a major role in the
      pathophysiology of polycystic ovary syndrome (PCOS), but the association of
      vitamin D with oxidative stress is still not known in PCOS. Objective: The goal
      of the present study was to evaluate the correlation between serum 25-hydroxy
      vitamin D and oxidative stress markers in PCOS group compared to control group.
      Materials and Methods: 60 PCOS women (20-40 yr old) and 90 healthy women as
      control group were participated in this case-control study. Fasting serum level
      of 25(OH) D, glucose, insulin, calcium, malondialdehyde (MDA), protein carbonyl
      (PC), also homeostasis model assessment for insulin resistance (HOMA-IR) and
      fasting glucose to insulin ratio (FGIR) were measured. Results: It was found that
      the mean of serum 25(OH)D was lower in the PCOS group (10.76+/-4.17) than in the
      control group (12.07+/-6.26) but this difference was not statistically
      significant (p=0.125). Fasting insulin, HOMA-IR and MDA were significantly higher
      in the PCOS patients as compared to the controls, whereas PC level did not differ
      for the two groups (p=0.156). No significant correlations were found between
      25(OH)D levels and oxidative stress markers (MDA and PC). Conclusion: The
      findings indicated no significant differences in the serum 25(OH)D levels between
      the PCOS patients and the matched controls. Also, no correlation was found
      between the serum vitamin D levels and oxidative stress markers in both groups.

PMID- 29202124
TI  - Combined protective effect of zinc oxide nanoparticles and melatonin on
      cyclophosphamide-induced toxicity in testicular histology and sperm parameters in
      adult Wistar rats.
AB  - Background: Cyclophosphamide (CP) has been known as an anticancer drug with
      several side effects on various organs such as a male reproductive system that
      can cause infertility. Objective: To evaluate the possible combined effects of
      zinc oxide nanoparticles (nZno) and melatonin (Mel) on sperm parameters and
      histopathological changes of the testis in CP-treated rats. Materials and
      Methods: 42 adult male Wistar rats were divided into six groups. GI: control,
      GII: 60 mg/kg/wk CP, GIII and GIV, 10 mg/kg/wk Mel and 5mg/kg/wk nZno and GV: 5
      mg/kg/wk nZno and 10 mg/kg/wk Mel were given 2 hr prior to CP injection,
      respectively,GVI: 5mg/kg/wk nZno and 10 mg/kg/wk Mel simultaneously. After 8 wk
      of treatment, rats were sacrificed and testis and epididymis were harvested for
      further evaluation. Results: The CP-treated group showed significant decreases in
      the body, testes and epididymis weights and sperm parameters (sperm count,
      viability, motility) with an increase abnormal sperms when compared with the
      control (p<0.001), as well as many histological alterations included decreased
      diameters of seminiferous tubules and Johnsen's Testicular Score (with
      degeneration, desquamation, multi-nucleated giant cell formation), whereas
      combined treatment (GV), showed more protective effects on CP-induced
      reproductive system damage compared with groups III or IV (p<0.001). Conclusion:
      These results suggest simultaneous administration of Mel and nZno have more
      effectively protections against CP-induced reproductive damage than Mel or nZno
      alone.

PMID- 29202125
TI  - Gaussian Process Regression (GPR) Representation in Predictive Model Markup
      Language (PMML).
AB  - This paper describes Gaussian process regression (GPR) models presented in
      predictive model markup language (PMML). PMML is an extensible-markup-language
      (XML) -based standard language used to represent data-mining and predictive
      analytic models, as well as pre- and post-processed data. The previous PMML
      version, PMML 4.2, did not provide capabilities for representing probabilistic
      (stochastic) machine-learning algorithms that are widely used for constructing
      predictive models taking the associated uncertainties into consideration. The
      newly released PMML version 4.3, which includes the GPR model, provides new
      features: confidence bounds and distribution for the predictive estimations. Both
      features are needed to establish the foundation for uncertainty quantification
      analysis. Among various probabilistic machine-learning algorithms, GPR has been
      widely used for approximating a target function because of its capability of
      representing complex input and output relationships without predefining a set of
      basis functions, and predicting a target output with uncertainty quantification.
      GPR is being employed to various manufacturing data-analytics applications, which
      necessitates representing this model in a standardized form for easy and rapid
      employment. In this paper, we present a GPR model and its representation in PMML.
      Furthermore, we demonstrate a prototype using a real data set in the
      manufacturing domain.

PMID- 29202126
TI  - The Role of Sex Work Pay in Moderating the Effect of Mobile Phone Solicitation on
      Condom Practices: An Analysis of Female Sex Workers in India.
AB  - Mobile phones remain a largely untapped resource in the ongoing challenge to
      address Female Sex Worker (FSW) health, including HIV prevention services, in
      India. An important step towards designing effective mobile phone-based
      initiatives for FSWs is clarifying the contextual influences of mobile phone
      solicitation on sexual risk behavior. In this paper, we extend previously
      identified associations between mobile phone solicitation and condom practices by
      examining whether this association is moderated by sex work pay and offer key
      considerations for future research and implementation. Specifically, we conducted
      an analysis among 589 Indian FSWs, where FSWs who did not use mobile phones to
      solicit clients had the lowest mean sex work pay (INR 394/ USD 6.54) compared to
      FSWs who used both mobile and traditional strategies (INR 563/ USD 9.34). Our
      analysis indicate low paid FSWs who used mobile phones concurrently with
      traditional strategies had 2.46 times higher odds of inconsistent condom use
      compared to low paid FSWs who did not use mobile phones for client solicitation.
      No such effect was identified among high paid FSWs. These findings also
      identified group level differences among FSWs reporting different mobile phone
      solicitation strategies, including violence, client condom use and HIV status.
      Our results indicate that low pay does moderate the association between mobile
      phone solicitation and condom practices, but only among a sub-set of low paid
      FSWs. These findings also demonstrate the utility of classification by different
      mobile phone solicitation strategies for accurate assessment of sexual risk among
      mobile phone soliciting FSWs. In turn, this paves the way for novel approaches to
      utilize mobile phones for FSW HIV prevention. We discuss one such example, a
      mobile phone-based rapid screening tool for acute HIV infection targeting Indian
      FSWs.

PMID- 29202127
TI  - Obesity Does Not Exacerbate the Protumorigenic Systemic Environment in Sarcoma
      Subjects.
AB  - Sarcomas are a rare but fatal tumor type that accounts for <1% of adult solid
      malignancies and ~15% of childhood malignancies. Although the use of
      immunotherapy is being actively investigated for other solid tumors, advances in
      immunotherapy for sarcoma patients are lacking. To better understand the systemic
      immune environment in sarcoma patients, we performed a detailed multiplex
      analysis of serum cytokines, chemokines, and protumorigenic factors from
      treatment-naive subjects with localized, high-grade sarcoma. Because obesity is a
      major healthcare issue in the United States, we additionally examined the effects
      of obesity on serum protein profiles in our sarcoma subject cohort. We found that
      the systemic host environment is profoundly altered to favor tumor progression,
      with epidermal growth factor, angiopoietin-2, vascular endothelial growth factor
      A, IL-6, IL-8, and MIP-1beta all increased relative to tumor-free controls (all p
      < 0.05). Surprisingly, we found that obesity did not exacerbate this
      protumorigenic profile, as epidermal growth factor and IL-8 decreased with
      increasing subject body mass index (both p < 0.05 versus normal or overweight
      subjects). The Th2-related cytokines IL-4, IL-5, and IL-13 were also decreased in
      the presence of obesity. Thus, although the systemic environment in sarcoma
      subjects favors tumor progression, obesity does not further aggravate the
      production of protumorigenic factors.

PMID- 29202129
TI  - Statistical Framework for Uncertainty Quantification in Computational Molecular
      Modeling.
AB  - As computational modeling, simulation, and predictions are becoming integral
      parts of biomedical pipelines, it behooves us to emphasize the reliability of the
      computational protocol. For any reported quantity of interest (QOI), one must
      also compute and report a measure of the uncertainty or error associated with the
      QOI. This is especially important in molecular modeling, since in most practical
      applications the inputs to the computational protocol are often noisy,
      incomplete, or low-resolution. Unfortunately, currently available modeling tools
      do not account for uncertainties and their effect on the final QOIs with
      sufficient rigor. We have developed a statistical framework that expresses the
      uncertainty of the QOI as the probability that the reported value deviates from
      the true value by more than some user-defined threshold. First, we provide a
      theoretical approach where this probability can be bounded using Azuma-Hoeffding
      like inequalities. Second, we approximate this probability empirically by
      sampling the space of uncertainties of the input and provide applications of our
      framework to bound uncertainties of several QOIs commonly used in molecular
      modeling. Finally, we also present several visualization techniques to
      effectively and quantitavely visualize the uncertainties: in the input, final
      QOIs, and also intermediate states.

PMID- 29202130
TI  - Early Experiences Porting the NAMD and VMD Molecular Simulation and Analysis
      Software to GPU-Accelerated OpenPOWER Platforms.
AB  - All-atom molecular dynamics simulations of biomolecules provide a powerful tool
      for exploring the structure and dynamics of large protein complexes within
      realistic cellular environments. Unfortunately, such simulations are extremely
      demanding in terms of their computational requirements, and they present many
      challenges in terms of preparation, simulation methodology, and analysis and
      visualization of results. We describe our early experiences porting the popular
      molecular dynamics simulation program NAMD and the simulation preparation,
      analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware
      platforms. We report our experiences with compiler-provided autovectorization and
      compare with hand-coded vector intrinsics for the POWER8 CPU. We explore the
      performance benefits obtained from unique POWER8 architectural features such as 8
      way SMT and its value for particular molecular modeling tasks. Finally, we
      evaluate the performance of several GPU-accelerated molecular modeling kernels
      and relate them to other hardware platforms.

PMID- 29202131
TI  - Multifunctional System for Observing, Measuring and Analyzing Stimulation-Evoked
      Neurochemical Signaling.
AB  - The ability to measure neurotransmitter activity using implanted electrochemical
      sensors offers researchers a potent technique for analyzing neural activity
      across specific neural circuitry. We have developed a wirelessly controlled
      device, WINCS Harmoni, to observe and measure neurotransmitter dynamics at up to
      four separate sensors, with high temporal and spatial resolution. WINCS Harmoni
      also incorporates a versatile neurostimulator that can be synchronized with
      electrochemical recording. The WINCS Harmoni platform is thus optimally suited
      for probing the neurochemical effects of neurostimulation, and may in turn enable
      the development of personalized therapies for multiple brain disorders.

PMID- 29202128
TI  - "Toll-free" pathways for production of type I interferons.
AB  - Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular
      patterns (DAMPs) are recognized by different cellular pathogen recognition
      receptors (PRRs), which are expressed on cell membrane or in the cytoplasm of
      cells of the innate immune system. Nucleic acids derived from pathogens or from
      certain cellular conditions represent a large category of PAMPs/DAMPs that
      trigger production of type I interferons (IFN-I) in addition to pro-inflammatory
      cytokines, by specifically binding to intracellular Toll-like receptors or
      cytosolic receptors. These cytosolic receptors, which are not related to TLRs and
      we call them "Toll-free" receptors, include the RNA-sensing RIG-I like receptors
      (RLRs), the DNA-sensing HIN200 family, and cGAS, amongst others. Viruses have
      evolved myriad strategies to evoke both host cellular and viral factors to evade
      IFN-I-mediated innate immune responses, to facilitate their infection,
      replication, and establishment of latency. This review outlines these "Toll-free"
      innate immune pathways and recent updates on their regulation, with focus on
      cellular and viral factors with enzyme activities.

PMID- 29202132
TI  - Understanding Older Adult's Perceptions of Factors that Support Trust in Human
      and Robot Care Providers.
AB  - As the population of older adults increase so will the need for care providers,
      both human and robot. Trust is a key aspect to establish and maintain a
      successful older adult-care provider relationship. However, due to trust
      volatility it is essential to understand it within specific contexts. This
      proposed mixed methods study will explore what dimensions of trust emerge as
      important within the human-human and human-robot dyads in older adults and care
      providers. First, this study will help identify key qualities that support trust
      in a care provider relationship. By understanding what older adults perceive as
      needing to trust humans and robots for various care tasks, we can begin to
      provide recommendations based on user expectations for design to support trust.

PMID- 29202134
TI  - Subject-specific Estimation of Missing Cortical Thickness Maps in Developing
      Infant Brains.
AB  - To accurately chart the dynamic brain developmental trajectories in infants, many
      longitudinal neuroimaging studies prefer having a complete dataset.
      Unfortunately, missing data at certain time points are unavoidable in
      longitudinal datasets. To better use incomplete longitudinal data, we propose a
      novel method to estimate the subject-specific vertex-wise cortical thickness maps
      at missing time points, by using a customized regression forest, Dynamically
      Assembled Regression Forest (DARF). DARF ensures spatial smoothness of the
      estimated cortical thickness maps and also the computational efficiency. The
      proposed method can fully exploit the available information from the subjects
      both with and without missing scans. Our method has been applied to estimate the
      missing cortical thickness maps in a longitudinal infant dataset, which includes
      31 healthy subjects, with each having up to 5 scans. The experimental results
      indicate that our method can accurately estimate missing cortical thickness maps,
      with the average vertex-wise error less than 0.23 mm.

PMID- 29202133
TI  - The accuracy of hospital ICD-9-CM codes for determining Sickle Cell Disease
      genotype.
AB  - Sickle cell disease affects more than 100,000 individuals in the United States,
      among whom disease severity varies considerably. One factor that influences
      disease severity is the sickle cell disease genotype. For this reason, clinical
      prevention and treatment guidelines tend to differentiate between genotypes.
      However, previous research suggests caution when using a claimsbased
      determination of sickle cell disease genotype in healthcare quality studies. The
      objective of this study was to describe the extent of miscoding for the major
      sickle cell disease genotypes in hospital discharge data. Individuals with sickle
      cell disease were identified through newborn screening results or
      hemoglobinopathy specialty care centers, along with their sickle cell disease
      genotypes. These genotypes were compared to the diagnosis codes listed in
      hospital discharge data to assess the accuracy of the hospital codes in
      determining sickle cell disease genotype. Eighty-three percent (sickle cell
      anemia), 23% (Hemoglobin SC), and 31% (Hemoglobin Sbeta+ thalassemia) of
      hospitalizations contained a diagnosis code that correctly reflected the
      individual's true sickle cell disease genotype. The accuracy of the sickle cell
      disease genotype coding was indeterminate in 11% (sickle cell anemia), 12%
      (Hemoglobin SC), and 7% (Hemoglobin Sbeta+ thalassemia) and incorrect in 3%
      (sickle cell anemia), 61% (Hemoglobin SC), and 52% (Hemoglobin Sbeta+
      thalassemia) of the hospitalizations. The use of ICD-9-CM codes from hospital
      discharge data for determining specific sickle cell disease genotypes is
      problematic. Research based solely on these or other types of administrative data
      could lead to incorrect understanding of the disease.

PMID- 29202135
TI  - LATEST: Local AdapTivE and Sequential Training for Tissue Segmentation of
      Isointense Infant Brain MR Images.
AB  - Accurate segmentation of isointense infant (~6 months of age) brain MRIs is of
      great importance, however, a very challenging task, due to extremely low tissue
      contrast caused by ongoing myelination processes. In this work, we propose a
      novel learning method based on Local AdapTivE and Sequential Training (LATEST)
      for segmentation. Specifically, random forest technique is employed to train a
      local classifier (a single decision tree) for each voxel in the common space
      based on the neighboring training samples from atlases. Then, for each given
      voxel, all trained nearby individual classifiers (decision trees) are grouped
      together to form a forest. Moreover, the estimated probabilities are further used
      as additional source images to train the next set of local classifiers for
      refining tissue classification. By iteratively training the subsequent
      classifiers based on the updated tissue probability maps, a sequence of local
      classifiers can be built for accurate tissue segmentation.

PMID- 29202136
TI  - Explaining Radiological Emphysema Subtypes with Unsupervised Texture Prototypes:
      MESA COPD Study.
AB  - Pulmonary emphysema is traditionally subcategorized into three subtypes, which
      have distinct radiological appearances on computed tomography (CT) and can help
      with the diagnosis of chronic obstructive pulmonary disease (COPD). Automated
      texture-based quantification of emphysema subtypes has been successfully
      implemented via supervised learning of these three emphysema subtypes. In this
      work, we demonstrate that unsupervised learning on a large heterogeneous database
      of CT scans can generate texture prototypes that are visually homogeneous and
      distinct, reproducible across subjects, and capable of predicting accurately the
      three standard radiological subtypes. These texture prototypes enable automated
      labeling of lung volumes, and open the way to new interpretations of lung CT
      scans with finer subtyping of emphysema.

PMID- 29202137
TI  - Non-visual Web Browsing: Beyond Web Accessibility.
AB  - People with vision impairments typically use screen readers to browse the Web. To
      facilitate non-visual browsing, web sites must be made accessible to screen
      readers, i.e., all the visible elements in the web site must be readable by the
      screen reader. But even if web sites are accessible, screen-reader users may not
      find them easy to use and/or easy to navigate. For example, they may not be able
      to locate the desired information without having to listen to a lot of irrelevant
      contents. These issues go beyond web accessibility and directly impact web
      usability. Several techniques have been reported in the accessibility literature
      for making the Web usable for screen reading. This paper is a review of these
      techniques. Interestingly, the review reveals that understanding the semantics of
      the web content is the overarching theme that drives these techniques for
      improving web usability.

PMID- 29202138
TI  - Effects and time-kill assessment of amoxicillin used in combination with
      chloramphenicol against bacteria of clinical importance.
AB  - With the emergence of multidrug-resistant organisms in an era when drug
      development faces challenges causing pharmaceutical companies to curtail or
      abandon research on anti-infective agents, the use of combined existing
      antimicrobial agents may be an alternative. This study evaluated the effects of
      combining amoxicillin and chloramphenicol, to which many bacteria have become
      resistant, in vitro against Gram positive and Gram negative bacteria by agar
      diffusion, checkerboard and time-kill assays. The test isolates were susceptible
      to amoxicillin with minimum inhibitory concentrations (MICs) ranging between
      0.448 and 500 ug/ml and between 1.953 and 31.25 ug/ml for chloramphenicol. Upon
      combining these agents, there was a drastic reduction in their MICs indicating an
      increased antibacterial activity that showed synergistic interaction against all
      the bacteria. At the highest concentrations, the inhibition zones ranges were
      20.33-38.33+/-0.58 ug/ml for amoxicillin, 27.67-37.67+/-0.58 ug/ml for
      chloramphenicol and 31.67-39.33+/-0.58 ug/ml for the combined agents. The
      fractional inhibitory concentration indices (FICIs) showed synergy ranging from
      0.129 to 0.312 while FICIs for additive interaction were between 0.688 and 1.0.
      There was no antagonistic interaction. At the 1/2MICs of the combined
      antibiotics, all the tested bacteria, except for Klebsiella pneumoniae ATCC 4352,
      Proteus vulgaris CSIR 0030 and Enterococcus cloacae ATCC 13047 were eliminated
      before 24 h. At the MICs, all the tested bacteria were eliminated except
      Enterococcus cloacae ATCC 13047 which was almost totally eliminated. Post
      antibiotic assessment after 48 h showed that all the cultures were sterile except
      for that of Enterococcus cloacae ATCC 13047. The lack of antagonism between these
      antibacterial agents in checkerboard and time-kill assays suggested that
      combining amoxicillin with chloramphenicol can provide an improved therapy in
      comparison to the use of each antibiotic individually. The study indicates the
      potential beneficial value of combining amoxicillin and chloramphenicol in the
      treatment of microbial infections in clinical settings.

PMID- 29202139
TI  - Changes in the pancreas caused by different types of hypertension.
AB  - Hypertension is considered a lifestyle disease. Unfavorable forecasts predict a
      significant increase in the number of patients suffering from this disorder. Many
      changes in various organs have been observed as a result of ischemia. An
      interesting question arises of whether differences between the mechanisms
      occurring in different types of hypertension could produce different effects in
      the organs. It is well known that there is a close relationship between
      hypertension and insulin resistance. On the other hand, insulin resistance is the
      main cause of type 2 diabetes, which develops in parallel with changes in the
      pancreas. The pancreas is a very important organ since it produces enzymes
      crucial for the digestive process, as well as performs an important endocrine
      function. The work presented here focuses primarily on the latter issue. The
      authors present an overview of contemporary literature concerning the influence
      of different types of hypertension on the function of the pancreas.

PMID- 29202141
TI  - Let's get physical!

PMID- 29202140
TI  - Relation of the polymorphism of cyp51A sequence and the susceptibility of
      Aspergillus fumigatus isolates to triazoles determined by commercial gradient
      test (Etest) and by reference methods.
AB  - The aim of this study was to evaluate the accuracy of commercial gradient test
      (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates
      using reference microdilution methods and the analysis of sequences of the cyp
      51A gene. The study was performed on twenty clinical isolates which were
      identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2
      fragment of ribosomal DNA and the beta-tubulin gene, out of them seventeen
      isolates showed wild-type cyp51A sequence and three were positive for the
      mutation TR34/L98H. All isolates were tested for the susceptibility to
      itraconazole (ITZ), voriconazole (VOR) and posaconasole (POS) using microdilution
      methods, according to EUCAST and CLSI protocols, as well as using Etest. The
      results of microdilution and Etests were analysed separately according to
      clinical breakpoints (CBP) defined by EUCAST version 7.0 and epidemiological cut
      off values (ECV). Etest as well as reference methods excellently recognised the
      WT isolates, which were susceptible to all tested triazoles, regardless of the
      method and CBP or ECV criteria used. The Etest recognized three non-WT isolates
      as resistant or intermediately sensitive to ITZ and POS and one as resistant to
      VOR. The categorical concordance between Etests and EUCAST and Etests and the
      CLSI method ranged from 90 to 100%. The interpretation of the results obtained
      from routine A. fumigatus Etests requires great caution. The use of the
      confirmative examinations with reference AST methods as well as with molecular
      tests is recommended.

PMID- 29202142
TI  - Antibiotic overprescribing: Still a major concern.
AB  - Despite universal agreement that antibiotic overprescribing is a problem, the
      practice continues to vex us. Antibiotic use--whether appropriate or not--has
      been linked to rising rates of antimicrobial resistance, disruption of the gut
      microbiome leading to Clostridium difficile infections, allergic reactions, and
      increased health care costs. And yet, physicians continue to overprescribe this
      class of medication. A 2016 Centers for Disease Control and Prevention report
      estimates that at least 30% of antibiotics prescribed in US outpatient settings
      are unnecessary. Another report cites a slightly higher figure across a variety
      of health care settings. Pair these findings with the fact that there are
      currently few new drugs in development to target resistant bacteria, and you have
      the potential for a post-antibiotic era in which common infections could become
      lethal. Family practitioners are on the front lines of this battle. Here's what
      we can do now.

PMID- 29202143
TI  - The evaluation and management of female sexual dysfunction.
AB  - Female sexual dysfunction has complex physiologic and psychological components
      that require a detailed screening, history, and physical examination. Our goal in
      this review is to provide family physicians with insights and practical advice to
      help screen, diagnose, and treat female sexual dysfunction, which can have a
      profound impact on patients' most intimate relationships.

PMID- 29202144
TI  - Best uses of osteopathic manipulation.
AB  - With the growing number of DOs and the high utilization of osteopathic
      manipulative treatment (OMT), it is important for all physicians to understand
      the role OMT can play in the treatment of conditions ranging from low back pain
      to irritable bowel syndrome so that patients may be offered, or referred for, the
      treatment when appropriate.

PMID- 29202145
TI  - The benefits of physician-pharmacist collaboration.
AB  - Over the past decade, physician-pharmacist collaborative practices have gained
      traction in primary care as a way to implement team-based-care models. And there
      is evidence pointing to the effectiveness of this multidisciplinary heath care
      team approach, in which pharmacists are typically responsible for such things as
      obtaining medication histories, identifying barriers to adherence, and adjusting
      medication regimens. Several studies have shown the significant impact that
      physician-pharmacist collaborative management (PPCM) can have on blood pressure
      control among patients with hypertension. Additionally, PPCM may have positive
      effects on HbA1c reduction and diabetes control, suggesting that benefits may
      extend to other chronic diseases, too.

PMID- 29202147
TI  - Segmental distribution of nodules on trunk.
AB  - A 70-year-old Caucasian man presented with a longstanding history of numerous
      nontender, fleshy, skin-colored papules on his trunk, ranging from 3 to 8 mm in
      size. They were noted incidentally during an examination of unrelated nonhealing
      lesions on the patient's left cheek. He said the lesions on his trunk first
      appeared when he was 28 years old and had continued to grow in size and number.
      The patient said his son had at least one similar lesion on his upper back, but
      otherwise there was no family history of these lesions. A biopsy was performed on
      one of the nodules. WHAT IS YOUR DIAGNOSIS? HOW WOULD YOU TREAT THIS PATIENT?

PMID- 29202146
TI  - PURLs: Does azithromycin have a role in cesarean sections?
AB  - A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm.
      The patient reached complete cervical dilation after artificial rupture of
      membranes and oxytocin augmentation. After 4 hours of pushing, there has been
      minimal descent of the fetal vertex beyond +1 station with significant caput
      succedaneum. Her physician decides to proceed with cesarean delivery. What
      antibiotics should be administered prior to incision to reduce postoperative
      infection?

PMID- 29202148
TI  - Behavioral Health Consult: Ensuring prompt recognition and treatment of panic
      disorder.
AB  - Lorna D was seen by her primary care physician as follow-up to a visit she made
      to the emergency department (ED). The 37 year old had gone to the ED 4 times in
      the previous year. Each time she presented with tachycardia, dyspnea, nausea,
      numbness in her extremities, and a fear that she was having a heart attack. In
      spite of negative work-ups at each visit (electrocardiogram, cardiac enzymes,
      complete blood count, toxicology screen, Holter monitoring), Ms. D was terrified
      that the ED doctors were missing something. She was still "rattled" by the chest
      pain and shortness of breath she had experienced. Mild symptoms were persisting
      and she was worried that she would have a heart attack and die without the
      treatment she believed she needed. How would you proceed with this patient?

PMID- 29202149
TI  - Clinical Inquiries: Which interventions are effective in managing parental
      vaccine refusal?
AB  - It's unclear whether educational initiatives alone alter vaccine refusal.
      Although about a third of parents cite herd immunity as motivation for
      vaccination, its efficacy in addressing vaccine hesitancy isn't clear.
      Multifaceted interventions (encompassing improved access to vaccines,
      immunization mandates, and patient education) may produce a >=25% increase in
      vaccine uptake in groups with vaccine hesitancy and low utilization. Correcting
      false information about influenza vaccination improves perceptions about the
      vaccine, but may decrease intention to vaccinate in parents who already have
      strong concerns about safety. Discussions about vaccines that are more
      paternalistic (presumptive rather than participatory) are associated with higher
      vaccination rates, but lower visit satisfaction. Providers should thoroughly
      address patient concerns about safety and encourage vaccine use.

PMID- 29202150
TI  - Erythematous, friable nipple with loss of protrusion . history of breastfeeding .
      Dx?
AB  - A 34-year-old healthy woman presented to the breast surgical oncology clinic with
      skin changes to her left nipple after being referred by her primary care
      provider. She attributed the skin changes to shearing from breastfeeding her
      third child 5 years earlier. Physical examination revealed an erythematous and
      friable nipple with loss of protrusion. The patient reported routine bleeding
      from her nipple, but said the skin changes had remained stable and denied any
      breast masses. The patient's last mammogram was 2.5 years earlier and had only
      been remarkable for bilateral benign calcifications.

PMID- 29202151
TI  - Screening for tuberculosis: Updated recommendations.
AB  - Tuberculosis (TB) remains a significant public health problem worldwide with an
      estimated 10.4 million new cases and 1.7 million deaths having occurred in 2016.
      In that same year, there were 9287 new cases in the United States--the lowest
      number of TB cases on record. TB appears in one of 2 forms: active disease, which
      causes symptoms, morbidity, and mortality and is a source of transmission to
      others; and latent TB infection (LTBI), which is asymptomatic and noninfectious
      but can progress to active disease. The estimated prevalence of LTBI worldwide is
      23%, although in the United States it is only about 5%. The proportion of those
      with LTBI who will develop active disease is estimated at 5% to 10% and is highly
      variable depending on risks. In the United States, about two-thirds of active TB
      cases occur among those who are foreign born, whose rate of active disease is
      14.6/100,000. Five countries account for more than half of foreign-born cases:
      Mexico, the Philippines, India, Vietnam, and China.

PMID- 29202152
TI  - Subacute loss of vision in one eye . rash on hands and feet . plaques with
      scaling on genitals . Dx?
AB  - A 67-year-old man presented to the hospital with subacute loss of vision in his
      left eye. The visual changes began 2 weeks earlier, with a central area of visual
      loss that had since progressed to near complete vision loss in the left eye.
      Physical examination revealed patchy alopecia, a scaling and hyperkeratotic rash
      of his hands and feet, and blanching, erythematous plaques with associated
      scaling on the scrotum and glans penis. Ophthalmologic examination revealed 1/200
      vision in his left eye with a large plaque occupying a substantial portion of the
      superior quadrant, smaller perifoveal plaques in both of his eyes, and a small
      infiltrate above the left optic nerve head. The patient also described fatigue,
      loss of taste, and an unintentional weight loss of 7 to 10 kg over the previous 6
      months. He had seen his primary care provider 3 months prior for a burning
      sensation and scaling rash on his feet and hands, and was prescribed a topical
      steroid.

PMID- 29202153
TI  - Congressional Politics and Peer Review.
AB  - U.S. Senator Rand Paul (R-KY) believes that the public is better served by
      changing how peer review is conducted of research grant applications for federal
      money. Toward that end, on October 17, 2017, he introduced S. 1973, the BASIC
      Research Act, as a means of curtailing what he considers silly research. If
      enacted, the following would result.

PMID- 29202154
TI  - Changing Student Attitudes Toward Interprofessional Learning and Collaboration:
      Evidence for the Effectiveness of Partnering with Healthcare Mentors in the
      Academic Setting.
AB  - PURPOSE: Individuals living with chronic health conditions serving as healthcare
      mentors (HCM) allow the creation of high impact, authentic learning experiences.
      The purpose of this study was to examine the effectiveness of a 6-hour curricular
      experience involving HCM in changing student attitudes toward interprofessional
      learning (IPL) and collaboration (IPC). METHODS: Thirty-eight students from
      clinical psychology, nursing, physical therapy, and social work programs
      participated in either the learning intervention (n=19) or the control group
      (n=19). Students in the IPL group examined the HCMs, who were diagnosed with
      multiple sclerosis, shared the findings during an interprofessional team meeting,
      and collaboratively developed consensus-based interprofessional care
      recommendations. The Interdisciplinary Education Perception Scale, Readiness for
      Interprofessional Learning Scale, and Attitudes Toward Health Care Teams Scale
      were completed pre- and post-IPL. In addition, discipline-specific focus groups
      were also conducted. RESULTS: The IPL experience resulted in positive changes in
      student attitudes toward teamwork and collaboration. Teamwork among the students
      was reportedly characterized by open communication, mutual respect, and the
      incorporation of ideas from other disciplines. CONCLUSIONS: Positively changing
      students' attitudes and skills for IPC prior to licensure is an important first
      step in providing coordinated interprofessional care to patients/clients living
      with chronic health conditions.

PMID- 29202156
TI  - Informed Consent and the Limited English Patient: A Pilot Project with Dental
      Hygiene Students to Assess Student Knowledge, Perceptions, and Attitudes.
AB  - Informed consent is the process by which a patient agrees to or rejects a
      proposed plan of treatment after a discussion with the provider about the
      benefits, risks, and alternative treatments available. In the United States, a
      signed informed consent form is required before any treatment plan may be
      implemented. However, there is no literature addressing how students in health
      professions understand informed consent in the context of encounters with limited
      English proficient (LEP) patients. The purpose of this interprofessional,
      interdisciplinary pilot project was to explore and assess Idaho State
      University's dental hygiene students' knowledge, perceptions, and attitudes
      associated with the process of informed consent when working with LEP patients in
      a dental hygiene setting. Using mixed-methods methodology, we administered a pre
      immersion survey to 28 second-year dental hygiene students. These students then
      participated in a simulated encounter with Spanish-speaking mock-patients and
      trained interpreters. After the immersive experience, students completed a post
      immersion survey. Study results indicate overall positive increases in student
      knowledge, perceptions, and attitudes toward various aspects of the provider-LEP
      patient encounter.

PMID- 29202155
TI  - Changes in Health Professional Students' Attitudes Toward the Underserved: Impact
      of Extended Participation in an Interprofessional Student-Run Free Clinic.
AB  - This study assessed the impact of volunteering for 2 years in an
      interprofessional student-run free clinic (SRFC) on the attitudes of health
      professional students toward the medically underserved. The Health Professionals'
      Attitudes Toward the Homeless Inventory was administered to students from six
      different health professions at three time points: before, after 1 year, and
      after 2 years of volunteering in an SRFC. The results were compared to students
      who never applied to the SRFC and those who applied but were not accepted.
      Students who applied had similar attitude scores at baseline and differed
      significantly from those who did not apply. Although all three groups showed
      declining attitudes after the first year, students who volunteered had more
      favorable attitudes than the other two groups from this point forward. These
      results suggest that SRFCs have a protective effect against the declining
      attitudes toward the underserved that can occur as training progresses.

PMID- 29202157
TI  - Utilization of Ambulatory Physical Therapy and Occupational Therapy by the United
      States Population, 2009-2013.
AB  - PURPOSE: The aging of the U.S. population and insurance reforms in the Patient
      Protection and Affordable Care Act of 2010 have been postulated to increase
      future demand for physical therapy and occupational therapy. The purpose of this
      study was to develop population estimates for and describe the demographic
      characteristics of persons using ambulatory physical therapy and occupational
      therapy during 2009-2013. METHOD: From data from the Medical Expenditure Panel
      Survey-Household Component, population estimates of the number of persons
      utilizing ambulatory therapy services were developed for the total U.S.
      population and by selected demographic characteristics: age, sex, census region,
      race/ethnicity and income category. RESULTS: The ambulatory therapy patient
      population grew by an average rate of 5.9% to a total of 13.2 million persons in
      2013. The average annual growth rate was higher for persons aged 0-17, age over
      64, Asian-Americans, Black Americans, and persons living in low income and near
      poor households. The typical user was a working-age, Caucasian female living in a
      middle or high income household. CONCLUSIONS: While the typical user of
      ambulatory therapy services represents persons who traditionally have good access
      to health care, the results of this study point to an aging of the population
      using therapy services and improved access to ambulatory therapy services for
      historically underserved populations.

PMID- 29202158
TI  - Therapeutic Value of Medical Marijuana in New Jersey Patients: A Community
      Partnership Research Endeavor.
AB  - OBJECTIVE: The Public Health Program at Stockton University partnered with the
      Compassionate Care Foundation to ascertain the impact of medical marijuana on
      patients in New Jersey. METHODS: Patients volunteered to complete a survey once a
      month for 8 months. The survey explored their use, form, and strain of medical
      marijuana and its influence on pain and 12 other physical and mental health
      variables. Also, an increase or decrease in other medication taken and any
      unexpected outcomes were recorded. RESULTS: From a total of 955 patients,
      patients responding to the surveys varied from 501 for visit 1, 290 for visit 2,
      to 179 for visit 3. Results provide insight into the diagnoses for which patients
      used medical marijuana. Results indicate increased mood, general overall
      condition, and energy as the highest consequences; level of pain in the middle
      range; and most frequent usage as 3 to 4 times a day. Repeated measures done
      after visit 2 showed eight statistically significant differences for patients
      after using medical marijuana: an increase in general quality of life, mobility,
      and mood, with a decrease in inflammation, intraocular pressure, spasms,
      seizures, and pain. Results after visit 3 indicated seven significant differences
      compared to visit 1: decreased seizures, intraocular pressure, spasms, nausea,
      and pain, along with increased energy and mobility. No differences were found by
      patient diagnosis or age, but sex-related differences occurred in inflammation,
      mood, and energy. CONCLUSION: Results support positive therapeutic benefits of
      medical marijuana, and despite methodological limitations, our study contributes
      to the growing body of literature.

PMID- 29202159
TI  - Mammographic Phantoms Frequently Used to Determine Image Quality: A Comparative
      Study.
AB  - : Appropriate diagnosis depends on the image quality of the mammographic system.
      Phantoms are normally used, since they have physical properties similar to those
      of different human tissues, and are important tools for quality assurance of
      mammography equipment, evaluation of image quality, and accurate determination of
      patient dosage. The aim of this study was to evaluate various mammographic
      phantoms used to determine the image quality of digital mammographic equipment.
      METHODS: Three phantoms were used: an American College of Radiology accreditation
      phantom, an MTM 100/R, and a tissue-equivalent phantom. Tungsten/silver
      target/filter material was used with four variable exposures (25, 28, 30, and 32
      kVp). In total, there were 12 images. The images were evaluated by scoring the
      visibility of the structures, and a total score out of 100% was recorded.
      Statistical analysis was conducted using non-parametric tests. RESULTS: There was
      no significant difference in the visibility of structures among the phantoms at
      different kVp. However, there were significant differences (p=0.04) in the
      visibility of the tumor masses when the kVp was varied. In addition, visibility
      rates differed significantly between the three phantoms (p<=0.05). CONCLUSION:
      All the phantoms used in this study were suitable for evaluating digital
      mammography systems. However, the exposure setting for evaluation must be
      carefully considered. The tissue-equivalent phantom performed better in terms of
      the visibility rate to assess image quality in the digital mammography units.

PMID- 29202160
TI  - Benefits and Challenges of Supervising Physical Therapy Students in the State of
      Kuwait: A National Study.
AB  - One common component of allied health education is clinical fieldwork. It is the
      bridge between the didactic curriculum and clinical practice. Clinical
      supervisors perceive that being a clinical supervisor has both benefits and
      challenges. A modified questionnaire was distributed to 75 physical therapists
      who had previously or were currently engaged in supervising physical therapy
      students in 12 public hospitals in the State of Kuwait. In addition to
      demographic data, the questionnaire asked about the benefits and challenges
      associated with supervising students. The results indicated that the clinical
      fieldwork supervisors regarded their student supervision process as highly
      beneficial and reported that it improved their professionalism, problem-solving
      skills, and clinical reasoning. Challenges to supervision included students' lack
      of theoretical knowledge, poor hands-on skills, and poor writing/documentation
      skills. Suggestions are put forth to promote additional benefits and overcome
      existing challenges to develop a more successful physical therapy clinical
      education process for the supervisors and the students.

PMID- 29202161
TI  - Development of an Academic Professional Behaviors Assessment for Health
      Professions Faculty.
AB  - PURPOSE: An important component in educating health professionals is developing
      professional behaviors, which includes appropriate modeling by faculty. The
      purposes of this study were to: 1) determine examples of behaviors that faculty
      identify as important in measuring professional behaviors in themselves and
      colleagues, and 2) develop a tool that could be used in self- and peer-assessment
      for faculty. METHODS: Part I of this two-part study was a survey to determine
      which behaviors are considered valuable in seven categories of professional
      behaviors. Part II surveyed 113 faculty members across seven disciplines in one
      College of Health Professions to rank behaviors identified in Part I. Behaviors
      scored more than 2 SD below the mean were eliminated, and one-way ANOVA
      calculations were used to assess differences in rankings between professions.
      RESULTS: In Part I, 95 of 154 total behaviors were identified as most important
      at the end of round one; in round two, that number was reduced to 54. In Part II,
      46 of the 54 behaviors were ranked as most important with no significant
      differences among programs. The Academic Faculty Professional Behavior Assessment
      was developed from these behaviors. CONCLUSION: Results of this study led to the
      development of an assessment tool which can be used across various health
      professions faculty.

PMID- 29202162
TI  - Controversial Issues in Healthcare Policy: A Survey of Doctor of Physical Therapy
      Students in a Public University.
AB  - BACKGROUND: The recently passed legislation and proposed policy changes governing
      the healthcare system have been met with extensive debate and controversy.
      OBJECTIVE: The primary objective of the study was to determine the attitudes of
      Doctor of Physical Therapy (DPT) students towards some of these controversial
      issues. The secondary objective was to determine the demographic factors,
      including number of years in a physical therapy program, that contribute to their
      attitude formation. METHODS: The research design was a cross-sectional non
      experimental survey. Purposive sampling was used to recruit subjects in a public
      university. Subjects took the survey including nine Likert scale
      questions/statements on controversial issues inspired from legislative efforts
      and news media sources and one open-ended question. RESULTS: Of the 111
      recruited, 106 students agreed to participate as subjects and completed the
      survey. Only 18.9% agreed or strongly agreed that the Patient Protection and
      Affordable Care Act is a positive solution for the healthcare system in America.
      Political affiliation, class level, and developmental environment were associated
      with a few questions/statements. CONCLUSIONS: DPT students in the sample had very
      diverse attitudes towards controversial issues in healthcare policy. Some of
      these attitudes revealed very different paradigms from the results found among
      medical students and the general public.

PMID- 29202163
TI  - Amount of Genetics Education is Low Among Didactic Programs in Dietetics.
AB  - Nutritional genomics is a growing area of research. Research has shown registered
      dietitian nutritionists (RDNs) have limited knowledge of genetics. Limited
      research is available regarding how didactic programs in dietetics (DPDs) meet
      the genetics knowledge requirement of the Accreditation Council for Education in
      Nutrition and Dietetics (ACEND(r)). The purpose of this study was to determine
      the extent to which the study of nutritional genomics is incorporated into
      undergraduate DPDs in response to the Academy of Nutrition and Dietetics position
      statement on nutritional genomics. The sample included 62 DPD directors in the
      U.S. Most programs (63.9%) reported the ACEND genetics knowledge requirement was
      being met by integrating genetic information into the current curriculum.
      However, 88.7% of programs reported devoting only 1-10 clock hours to genetics
      education. While 60.3% of directors surveyed reported they were confident in
      their program's ability to teach information related to genetics, only 6
      directors reported having specialized training in genetics. The overall amount of
      clock hours devoted to genetics education is low. DPD directors, faculty, and
      instructors are not adequately trained to provide this education to students
      enrolled in DPDs. Therefore, the primary recommendation of this study is the
      development of a standardized curriculum for genetics education in DPDs.

PMID- 29202164
TI  - Lessons Learned by a Founding Dean: College of Health and Human Services at
      Western Kentucky University.
AB  - This article describes the process in the development and implementation of the
      College of Health and Human Services at Western Kentucky University. Lessons
      learned and insights gained as an inaugural dean are presented around four main
      themes: creating a culture of trust and transparency, leaders of change,
      strategic planning, and cultivating external resources. The application of change
      theory, transformational leadership, and systems thinking enabled the college to
      more than double its enrollment and to address critical workforce needs in health
      and human services. Using these themes, the role of a dean is to be a "builder"-
      building trust through empowerment that leads to the offering of academic
      programs that meet community needs.

PMID- 29202165
TI  - A Survey of Undergraduate Capstone Course Objectives in Communication Sciences
      and Disorders: Current Trends and Future Implications.
AB  - PURPOSE: Undergraduate capstone courses are culminating experiences that allow
      seniors to integrate and demonstrate the knowledge and skills gained during
      undergraduate studies. To date, there are no published studies about capstone
      course standards/designs in the discipline of communication sciences and
      disorders (CSD). The purpose of this study was to determine what capstone
      experiences are considered critical for CSD undergraduates. METHOD: Faculty from
      CSD programs nationwide were asked to rank-order 15 potential learning objectives
      (suitable to a senior capstone) based on their relative importance from most
      important to least important. Some respondents provided feedback, which was
      optional. RESULTS: Sixty-four CSD faculty responded to the nationally distributed
      survey. The three highest ranked objectives for capstone courses were: written
      and oral communication proficiency, understanding of human communication, and
      understanding theories of learning from a multidisciplinary perspective.
      Undergraduate research experiences received the lowest rankings. CONCLUSION:
      Survey results and faculty feedback are discussed in the context of the standards
      expected of a capstone course, undergraduate requirements in CSD, and enhancing
      student interest in research. The degree to which students are being prepared for
      evidence-based practice, the doctoral shortage, and the challenges to master's
      programs are also discussed.

PMID- 29202166
TI  - Team-Based Learning at the End of a Physical Therapy Curriculum.
AB  - Team-based learning (TBL) is used in health professions education, including
      physical therapist education. This retrospective analysis assessed the
      implementation of TBL in a diagnostic screening course. Ninety-two Doctor of
      Physical Therapy and post-professional international master's students
      participated. The students' perceptions were assessed by the Team-Based Learning
      Student Assessment Inventory (TBL-SAI). The students overall scores on the TBL
      SAI demonstrated a favorable experience with TBL. The students also displayed
      positive responses on the three subscales: Accountability, Preference for Lecture
      or TBL, and Student Satisfaction. Open-ended comments revealed that the students
      liked the course and found it improved their teamwork skills. Further research at
      other institutions is needed to determine if implementing a TBL format late in
      the curriculum is equally as effective as demonstrated in the present study.

PMID- 29202167
TI  - Introduction of Virtual Patient Software to Enhance Physician Assistant Student
      Knowledge in Palliative Medicine.
AB  - PURPOSE: The purpose of this project was to infuse palliative medicine and end-of
      life care creatively into physician assistant (PA) education. METHODS: Nine
      second-year PA students volunteered to participate in this quasi-experimental,
      pretest-posttest pilot study. Students initially completed an anonymous survey
      evaluating seven domains of knowledge in palliative medicine coupled with a self
      assessment in competence. Virtual patient software was then used to simulate
      clinical encounters that addressed major palliative care domains. Upon completion
      of these cases, the same survey, with the addition of three questions about their
      own personal feelings, was administered. RESULTS: Overall response was positive
      in regard to improved knowledge and the virtual patient experience. After
      completion of the cases, students rated their self-assessed skills higher in all
      domains than prior to completing the cases. Factual knowledge scores showed a
      slight but not significant improvement, with an average pre-survey score of 4.56
      and post-survey score of 4.67. DISCUSSION: Using virtual patient software can be
      a way of infusing palliative medicine and end-of-life care into PA education.
      These encounters can then be modified to include interprofessional encounters
      within the health professions.

PMID- 29202168
TI  - What Do Faculty in Health Professions Need to be Competent Educators? Results
      from a School-Wide Needs Assessment.
AB  - BACKGROUND: Teaching may be the one responsibility most distinctly identified
      with being a faculty member, but may be the one for which faculty is least
      prepared. We performed a needs assessment to understand the educational needs of
      health professions faculty. METHODS: Faculty completed a survey examining the
      extent to which they valued and felt competent in 36 education-related skills
      within six categories, including instructional methods, curriculum development,
      assessment, instructional design, learners and learning, and diversity and
      inclusion. Participants rated each item using a 1 (not at all valuable/competent)
      to 5 (extremely valuable/competent) scale. RESULTS: Ninety-five percent of
      faculty (n=19/20) responded. Value means per topic included diversity and
      inclusion (4.61+/-0.65), instructional methods (4.60+/-0.28), learners and
      learning (4.60+/-0.34), assessment (4.54+/-0.31), instructional design (4.27+/
      0.50), and curriculum development (4.21+/-0.28). Self-rated competence was
      highest for diversity and inclusion (4.18+/-0.76), followed by learners and
      learning (3.76+/-0.75), instructional methods (3.73+/-0.65), assessment (3.22+/
      0.95), curriculum development (3.07+/-0.88), and instructional design (2.71+/
      0.77). All value/competency comparisons found the value of these skills skills to
      be significantly greater than competence in that category (p<0.001 for each),
      with largest discrepancies in instructional design and assessment. CONCLUSIONS:
      Opportunities exist to improve alignment between valued educator skills and their
      perceived competency levels in these skills.

PMID- 29202169
TI  - Psychological Impact of Cognitive Rest Following Sport-Related Concussion on Low
      Socioeconomic Status Adolescent Patients.
AB  - PURPOSE: Describe the psychological impact of cognitive rest in adolescents
      recovering from concussion from sport-related concussion. METHODS: Eight male
      football players with a previous sport concussion and full recovery completed
      semi-structured interviews during focus group sessions. Using content analysis,
      the researchers independently analyzed notes and transcriptions to identify
      themes associated with the psychological impact of cognitive rest. RESULTS:
      Common themes included: 1) sport as social support, and 2) boredom-complicated
      recovery following cognitive rest. CONCLUSIONS: The current treatment protocol
      indicating cognitive rest and removal from school and sport may be detrimental in
      a population that is peer-dependent. Future research should explore
      generalizability and additional factors that may complicate psychological
      recovery of adolescent athletes following concussive injuries.

PMID- 29202170
TI  - The DASS-14: Improving the Construct Validity and Reliability of the Depression,
      Anxiety, and Stress Scale in a Cohort of Health Professionals.
AB  - OBJECTIVES: Considerable research has been undertaken in evaluating the DASS-21
      in a variety of clinical populations, but studies of the instrument's
      psychometric adequacy in healthcare professionals is lacking. This study aimed to
      establish and improve the construct validity and reliability of the DASS-21 in a
      cohort of Australian health professionals. METHODS: 343 rehabilitation health
      professionals completed the DASS-21, along with a demographic questionnaire.
      Principal components analysis was performed to identify potential factors in the
      DASS-21. Factors were interpreted against theoretical constructs underlying the
      instrument. Items loading on separate factors were then subjected to reliability
      analysis to determine internal consistency of subscales. Items that demonstrated
      poor fit, or loaded onto more than one factor, were deleted to maximise the
      reliability of each subscale. RESULTS: Principal components analysis identified
      three dimensions (depression, anxiety, stress) in a modified version of the DASS
      21 (renamed DASS-14), with appropriate construct validity and good reliability
      (a=0.73 to 0.88). The three dimensions accounted for over 62% of variance between
      items. CONCLUSION: The modified DASS-14 scale is a more parsimonious measure of
      depression, anxiety, and stress, with acceptable reliability and construct
      validity, in rehabilitation health professionals and is appropriate for use in
      studies of similar populations.

PMID- 29202171
TI  - The Multiple Mini-Interview: A Possible Solution to Problems Associated with the
      Interview Processes for a Selected Entry Allied Health Program.
AB  - BACKGROUND: Concerns have been raised about the effectiveness of traditional semi
      structured interviews in selected entry allied health programs in terms of
      whether they give applicants the best opportunity to demonstrate their personal
      qualities and whether the process itself is overly intimidating and impersonal.
      This in turn raises questions about the reliability and validity of interviews.
      In this study, a possible alternative process was examined, the multiple mini
      interview (MMI). The study investigated the MMI's perceived acceptability for use
      by a speech-language pathology program. METHODS: The MMI was administered prior
      to the beginning of the academic year. The study involved 43 applicants and 5
      faculty members. On completion of the MMI, participants were invited to complete
      an optional questionnaire about their perceptions of the process. CONCLUSIONS:
      Overall, applicants indicated that they found the MMI process to be fair, simple,
      and non-threatening. The faculty members who interviewed the students also
      indicated that the process was fairer than the traditional interview, easier for
      them to manage because they could focus on one specific aspect of the interview
      process, and gave them an opportunity to meet all of the applicants.

PMID- 29202172
TI  - Interprofessional Collaboration of Dental Hygiene and Communication Sciences &
      Disorders Students to Meet Oral Health Needs of Children with Autism.
AB  - PURPOSE: This pilot project was intended to introduce an authentic
      interprofessional education experience with students from Communication Sciences
      & Disorders (CSD) and Dental Hygiene (DH) to develop and apply strategies to
      assist children diagnosed with autism spectrum disorder (ASD) to decrease their
      anxiety and improve their ability to participate in an oral screening and
      prophylaxis appointment. The second purpose was for students to learn each
      other's scope of practice. METHODS: Four children diagnosed with ASD were
      identified as having dental anxiety and unmet dental needs. The students
      collaborated to develop visual support strategies to support the implementation
      of an oral screening and prophylaxis. RESULTS: Three participants were able to
      participate in the oral screening, instruction for brushing teeth, and
      prophylaxis. The students reported having a better understanding of each other's
      roles and responsibilities and feeling more confident working with a child with
      ASD. CONCLUSION: The DH students were better able to identify the characteristics
      associated with ASD and to develop and use visual supports to assist children
      with ASD control anxiety during dental prophylaxis procedures. The CSD students
      learned techniques that hygienists use and how to help parents prepare their
      children for dental hygiene treatments.

PMID- 29202173
TI  - DCC/NTN1 complex mutations in patients with congenital hypogonadotropic
      hypogonadism impair GnRH neuron development.
AB  - Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease
      characterized by absent puberty and infertility due to GnRH deficiency, and is
      often associated with anosmia [Kallmann syndrome (KS)]. The genetic etiology of
      CHH is heterogeneous, and more than 30 genes have been implicated in
      approximately 50% of patients with CHH. We hypothesized that genes encoding axon
      guidance proteins containing fibronectin type-III (FN3) domains (similar to
      ANOS1, the first gene associated with KS), are mutated in CHH. We performed whole
      exome sequencing in a cohort of 133 CHH probands to test this hypothesis, and
      identified rare sequence variants (RSVs) in genes encoding for the FN3-domain
      encoding protein deleted in colorectal cancer (DCC) and its ligand Netrin-1
      (NTN1). In vitro studies of these RSVs revealed altered intracellular signaling
      associated with defects in cell morphology, and confirmed five heterozygous DCC
      mutations in 6 probands-5 of which presented as KS. Two KS probands carry
      heterozygous mutations in both DCC and NTN1 consistent with oligogenic
      inheritance. Further, we show that Netrin-1 promotes migration in immortalized
      GnRH neurons (GN11 cells). This study implicates DCC and NTN1 mutations in the
      pathophysiology of CHH consistent with the role of these two genes in the
      ontogeny of GnRH neurons in mice.

PMID- 29202175
TI  - Commentary on: Computer-Assisted Planning and 3D Printing-Assisted Modeling for
      Chin Augmentation.

PMID- 29202174
TI  - Autosomal and Mitochondrial Adaptation Following Admixture: A Case Study on the
      Honeybees of Reunion Island.
AB  - The honeybee population of the tropical Reunion Island is a genetic admixture of
      the Apis mellifera unicolor subspecies, originally described in Madagascar, and
      of European subspecies, mainly A. m. carnica and A. m. ligustica, regularly
      imported to the island since the late 19th century. We took advantage of this
      population to study genetic admixing of the tropical-adapted indigenous and
      temperate-adapted European genetic backgrounds. Whole genome sequencing of 30
      workers and 6 males from Reunion, compared with samples from Europe, Madagascar,
      Mauritius, Rodrigues, and the Seychelles, revealed the Reunion honeybee
      population to be composed on an average of 53.2 +/- 5.9% A. m. unicolor nuclear
      genomic background, the rest being mainly composed of A. m. carnica and to a
      lesser extent A. m. ligustica. In striking contrast to this, only 1 out of the 36
      honeybees from Reunion had a mitochondrial genome of European origin, suggesting
      selection has favored the A. m. unicolor mitotype, which is possibly better
      adapted to the island's bioclimate. Local ancestry was determined along the
      chromosomes for all Reunion samples, and a test for preferential selection for
      the A. m. unicolor or European background revealed 15 regions significantly
      associated with the A. m. unicolor lineage and 9 regions with the European
      lineage. Our results provide insights into the long-term consequences of
      introducing exotic specimen on the nuclear and mitochondrial genomes of locally
      adapted populations.

PMID- 29202177
TI  - Distinctive Neuroanatomical Substrates for Depression in Bipolar Disorder versus
      Major Depressive Disorder.
AB  - No neuroanatomical substrates for distinguishing between depression of bipolar
      disorder (dBD) and major depressive disorder (dMDD) are currently known. The aim
      of the current multicenter study was to identify neuroanatomical patterns
      distinct to depressed patients with the two disorders. Further analysis was
      conducted on an independent sample to enable generalization of results. We
      directly compared MR images of these subjects using voxel-based morphometry (VBM)
      and a support vector machine (SVM) algorithm using 1531 participants. The VBM
      analysis showed significantly reduced gray matter volumes in the bilateral
      dorsolateral prefrontal (DLPFC) and anterior cingulate cortices (ACC) in patients
      with dBD compared with those with dMDD. Patients with the two disorders shared
      small gray matter volumes for the right ACC and left inferior frontal gyrus when
      compared with healthy subjects. Voxel signals in these regions during SVM
      analysis contributed to an accurate classification of the two diagnoses. The VBM
      and SVM results in the second cohort also supported these results. The current
      findings provide new evidence that gray matter volumes in the DLPFC and ACC are
      core regions in displaying shared and distinct neuroanatomical substrates and can
      shed light on elucidation of neural mechanism for depression within the
      bipolar/major depressive disorder continuum.

PMID- 29202178
TI  - Clinical and translational science in cardiovascular research: highlights from
      the American Heart Association Scientific Sessions 2017: Changing view on the
      concept of cardiovascular risk and blood pressure targets.

PMID- 29202176
TI  - Distribution and Evolution of Peroxisomes in Alveolates (Apicomplexa,
      Dinoflagellates, Ciliates).
AB  - The peroxisome was the last organelle to be discovered and five decades later it
      is still the Cinderella of eukaryotic compartments. Peroxisomes have a crucial
      role in the detoxification of reactive oxygen species, the beta-oxidation of
      fatty acids, and the biosynthesis of etherphospholipids, and they are assumed to
      be present in virtually all aerobic eukaryotes. Apicomplexan parasites including
      the malaria and toxoplasmosis agents were described as the first group of
      mitochondriate protists devoid of peroxisomes. This study was initiated to
      reassess the distribution and evolution of peroxisomes in the superensemble
      Alveolata (apicomplexans, dinoflagellates, ciliates). We established
      transcriptome data from two chromerid algae (Chromera velia, Vitrella
      brassicaformis), and two dinoflagellates (Prorocentrum minimum, Perkinsus olseni)
      and identified the complete set of essential peroxins in all four reference
      species. Our comparative genome analysis provides unequivocal evidence for the
      presence of peroxisomes in Toxoplasma gondii and related genera. Our working
      hypothesis of a common peroxisomal origin of all alveolates is supported by
      phylogenetic analyses of essential markers such as the import receptor Pex5.
      Vitrella harbors the most comprehensive set of peroxisomal proteins including the
      catalase and the glyoxylate cycle and it is thus a promising model organism to
      investigate the functional role of this organelle in Apicomplexa.

PMID- 29202179
TI  - Extensively re-organized systemic lymph nodes provide a feasible environment for
      self-reactivity in lupus-prone NZB * NZW F1 mice.
AB  - Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus,
      although the immunological role of lymph nodes (LNs) in systemic autoimmunity
      remains largely unknown. Here, we performed comprehensive and systematic analyses
      of LNs in lupus-prone NZB * NZW F1 (BWF1) mice, demonstrating extensive tissue re
      organization of the systemic LNs with follicular expansion, hyper germinal center
      (GC) formation, atrophy of the paracortical T-cell area and expansion of the
      medulla in aged BWF1 mice bearing glomerulonephritis. The proportion of B cells
      was significantly increased in these reactive LNs but not in the spleen, and
      lymphocyte subsets involved in antibody production, i.e. GC B cells, follicular
      helper T cells and plasma cells, were elevated. Draining LNs of the affected
      organs, such as the renal and cervical nodes, showed enhanced tissue re
      organization and accumulation of effector lymphocytes, suggesting the presence of
      a positive feedback loop of regional responses. LN cells isolated from disease
      bearing animals produced anti-DNA antibody, indicating activation of autoreactive
      lymphocytes in situ. The substantial development of disease and LN alterations in
      mice that received a splenectomy at a young age points to the importance of other
      secondary lymphoid organs, most likely LNs, for the progression of autoimmune
      responses independent of the spleen. Taken together, our findings highlight the
      value of taking LN alterations and activities into consideration for
      understanding the pathogenesis of systemic autoimmunity.

PMID- 29202180
TI  - Emergence and Spread of Epidemic Multidrug-Resistant Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa (P. aeruginosa) is one of the most common nosocomial
      pathogens worldwide. Although the emergence of multidrug-resistant (MDR) P.
      aeruginosa is a critical problem in medical practice, the key features involved
      in the emergence and spread of MDR P. aeruginosa remain unknown. This study
      utilized whole genome sequence (WGS) analyses to define the population structure
      of 185 P. aeruginosa clinical isolates from several countries. Of these 185
      isolates, 136 were categorized into sequence type (ST) 235, one of the most
      common types worldwide. Phylogenetic analysis showed that these isolates fell
      within seven subclades. Each subclade harbors characteristic drug resistance
      genes and a characteristic genetic background confined to a geographic location,
      suggesting that clonal expansion following antibiotic exposure is the driving
      force in generating the population structure of MDR P. aeruginosa. WGS analyses
      also showed that the substitution rate was markedly higher in ST235 MDR P.
      aeruginosa than in other strains. Notably, almost all ST235 isolates harbor the
      specific type IV secretion system and very few or none harbor the CRISPR/CAS
      system. These findings may help explain the mechanism underlying the emergence
      and spread of ST235 P. aeruginosa as the predominant MDR lineage.

PMID- 29202181
TI  - Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to
      temozolomide.
AB  - Intrinsic therapeutic resistance especially in cancer stem cells (CSCs) together
      with extensive tumor cell infiltration and restricted permeation of the blood
      brain barrier (BBB) by drugs may all contribute to the treatment failure in
      patients with glioblastoma multiforme (GBM). Accumulating evidence suggests that
      long non-coding RNA (lncRNA), metastasis-associated lung adenocarcinoma
      transcript 1 (MALAT1) plays a role in tumor cell infiltration and therapeutic
      resistance of GBM. Using our tumor-targeted nanocomplex, we have modulated the
      expression of MALAT1 and investigated its impact on GBM cells. Importantly, our
      nanocomplex is able to target CSCs that are considered to be the prime culprits
      in therapeutic resistance and recurrence of GBM. Attenuation of MALAT1 by RNA
      interference significantly lowered the growth, motility and stemness of GBM
      cells. In addition, silencing of MALAT1 clearly improved the sensitivity of GBM
      cells to chemotherapeutic agents including the current first-line therapy of GBM
      [temozolomide (TMZ)]. In animal models of GBM, tumor involution with a modest but
      statistically significant survival benefit was achieved with concurrent treatment
      of TMZ and nanocomplex-mediated silencing of MALAT1. These results suggest that
      combining standard TMZ treatment with lncRNA-targeting therapies using our
      nanocomplex could substantially enhance the very poor prognosis for GBM patients.

PMID- 29202182
TI  - Capped RNA primer binding to influenza polymerase and implications for the
      mechanism of cap-binding inhibitors.
AB  - Influenza polymerase uses short capped primers snatched from nascent Pol II
      transcripts to initiate transcription of viral mRNAs. Here we describe crystal
      structures of influenza A and B polymerase bound to a capped primer in a
      configuration consistent with transcription initiation ('priming state') and show
      by functional assays that conserved residues from both the PB2 midlink and cap
      binding domains are important for positioning the capped RNA. In particular,
      mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap,
      significantly and specifically decreases cap-dependent transcription. We also
      compare the configuration of the midlink and cap-binding domains in the priming
      state with their very different relative arrangement (called the 'apo' state) in
      structures where the potent cap-binding inhibitor VX-787, or a close analogue, is
      bound. In the 'apo' state the inhibitor makes additional interactions to the
      midlink domain that increases its affinity beyond that to the cap-binding domain
      alone. The comparison suggests that the mechanism of resistance of certain
      mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be
      rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA
      binding as well as stabilization of the transcriptionally inactive 'apo' state.

PMID- 29202184
TI  - Consideration of insects as a source of dietary protein for human consumption.
AB  - Consumption of sufficient dietary protein is fundamental to muscle mass
      maintenance and overall health. Conventional animal-based protein sources such as
      meat (ie, beef, pork, lamb), poultry, fish, eggs, and dairy are generally
      considered high-quality sources of dietary protein because they meet all of the
      indispensable amino-acid requirements for humans and are highly digestible.
      However, the production of sufficient amounts of conventional animal-based
      protein to meet future global food demands represents a challenge. Edible insects
      have recently been proposed as an alternative source of dietary protein that may
      be produced on a more viable and sustainable commercial scale and, as such, may
      contribute to ensuring global food security. This review evaluates the protein
      content, amino-acid composition, and digestibility of edible insects and
      considers their proposed quality and potential as an alternative protein source
      for human consumption.

PMID- 29202185
TI  - Clinical documentation variations and NLP system portability: a case study in
      asthma birth cohorts across institutions.
AB  - Objective: To assess clinical documentation variations across health care
      institutions using different electronic medical record systems and investigate
      how they affect natural language processing (NLP) system portability. Materials
      and Methods: Birth cohorts from Mayo Clinic and Sanford Children's Hospital (SCH)
      were used in this study (n = 298 for each). Documentation variations regarding
      asthma between the 2 cohorts were examined in various aspects: (1) overall corpus
      at the word level (ie, lexical variation), (2) topics and asthma-related concepts
      (ie, semantic variation), and (3) clinical note types (ie, process variation). We
      compared those statistics and explored NLP system portability for asthma
      ascertainment in 2 stages: prototype and refinement. Results: There exist notable
      lexical variations (word-level similarity = 0.669) and process variations
      (differences in major note types containing asthma-related concepts). However,
      semantic-level corpora were relatively homogeneous (topic similarity = 0.944,
      asthma-related concept similarity = 0.971). The NLP system for asthma
      ascertainment had an F-score of 0.937 at Mayo, and produced 0.813 (prototype) and
      0.908 (refinement) when applied at SCH. Discussion: The criteria for asthma
      ascertainment are largely dependent on asthma-related concepts. Therefore, we
      believe that semantic similarity is important to estimate NLP system portability.
      As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic
      level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully
      with proper adjustments to deal with the intrinsic corpus heterogeneity.

PMID- 29202186
TI  - Noncalcemic adverse effects and withdrawals in randomized controlled trials of
      long-term vitamin D2 or D3 supplementation: a systematic review and meta
      analysis.
AB  - Context: Recent randomized controlled trials (RCTs) provide evidence for a
      possible beneficial impact of vitamin D supplementation on health outcomes beyond
      bone health, but there are few reviews of noncalcemic adverse effects from long
      term supplementation. Objective: The aims of this systematic review of vitamin D
      supplementation in RCTs were as follows: to determine whether all adverse
      effects, when combined, are reported equally between treatment arms; to identify
      the most common noncalcemic adverse effects reported; and to ascertain whether
      withdrawal rates, as a marker of clinical adverse effects, differ between
      treatment arms. Data Sources: The MEDLINE Ovid, Embase, and Cochrane Library
      databases were searched systematically up to May 2016. Study Selection:
      Randomized controlled trials that met the following criteria were selected:
      administered vitamin D2 or D3 supplements for a minimum supplementation or follow
      up period of 24 weeks, had a placebo/control group, and were conducted among
      adults (>= 18 y). Data Extraction: Two researchers independently screened studies
      for eligibility, extracted data, and carried out quality assessment of selected
      studies. A total of 128 studies with 52 297 participants were identified. A
      random-effects model was used to calculate risk ratios in a meta-analysis.
      Results: Long-term vitamin D2 or D3 supplementation, compared with placebo, did
      not increase all adverse effects, when combined, as reported in 62 studies with
      19 389 participants (relative risk [RR] = 0.97; 95%CI, 0.92-1.02). Vitamin D also
      did not increase the risk of the most common noncalcemic adverse effects:
      gastrointestinal symptoms were reported in 27 studies with 9189 participants (RR
      = 1.01; 95%CI, 0.87-1.17), and dermatological symptoms were reported in 8 studies
      with 1695 participants (RR = 1.33; 95%CI, 0.82-2.15). Vitamin D did not increase
      withdrawals from 123 studies with 41 861 participants (RR = 1.03; 95%CI, 0.96
      1.09). However, participants given vitamin D were more likely to report
      withdrawals than those given placebo in studies in which calcium was given in
      both arms (RR = 1.16; 95%CI, 1.02-1.33) when compared with participants in
      studies in which calcium was not given in either arm (RR = 1.00; 95%CI, 0.95
      1.06; P for interaction = 0.009). Conclusions: Overall, these findings suggest
      that vitamin D, by itself, does not increase the risk of noncalcemic adverse
      effects.

PMID- 29202187
TI  - Identifying Anastrepha (Diptera; Tephritidae) Species Using DNA Barcodes.
AB  - Molecular identification of fruit flies in the genus Anastrepha (Diptera;
      Tephritidae) is important to support plant pest exclusion, suppression, and
      outbreak eradication. Morphological methods of identification of this
      economically important genus are often not sufficient to identify species when
      detected as immature life stages. DNA barcoding a segment of the mitochondrial
      cytochrome oxidase I gene has been proposed as a method to identify pests in the
      genus. The identification process for these fruit flies, however, has not been
      explained in prior DNA barcode studies. DNA barcode methods assume that available
      DNA sequence records are biologically meaningful. These records, however, can be
      limited to the most common species or lack population-level measurements of
      diversity for pests. In such cases, the available data used as a reference are
      insufficient for completing an accurate identification. Using 539 DNA sequence
      records from 74 species of Anastrepha, we demonstrate that our barcoding data can
      distinguish four plant pests: Anastrepha grandis (Macquart) (Diptera;
      Tephritidae), Anastrepha ludens (Loew), Anastrepha serpentina (Wiedemann), and
      Anastrepha striata Schiner. This is based on genetic distances of barcode records
      for the pests and expert evaluation of species and population representation in
      the data set. DNA barcoding of the cytochrome oxidase I gene alone cannot
      reliably diagnose the pests Anastrepha fraterculus (Wiedemann), Anastrepha
      obliqua (Macquart), and Anastrepha suspensa (Loew).

PMID- 29202188
TI  - Estimating the causal effects of chronic disease combinations on 30-day hospital
      readmissions based on observational Medicaid data.
AB  - Objective: Demonstrate how observational causal inference methods can generate
      insights into the impact of chronic disease combinations on patients' 30-day
      hospital readmissions. Materials and Methods: Causal effect estimation was used
      to quantify the impact of each risk factor scenario (ie, chronic disease
      combination) associated with chronic kidney disease and heart failure (HF) for
      adult Medicaid beneficiaries with initial hospitalizations in 2 New York State
      counties. The experimental protocol: (1) created matched risk factor and
      comparator groups, (2) assessed covariate balance in the matched groups, and (3)
      estimated causal effects and their statistical significance. Causality lattices
      summarized the impact of chronic disease comorbidities on readmissions. Results:
      Chronic disease combinations were ordered with respect to their causal impact on
      readmissions. Of disease combinations associated with HF, the combination of HF,
      coronary artery disease, and tobacco abuse (in that order) had the highest causal
      effect on readmission rate (+22.3%); of disease combinations associated with
      chronic kidney disease, the combination of chronic kidney disease, coronary
      artery disease, and diabetes had the highest effect (+9.5%). Discussion: Multi
      hypothesis causal analysis reveals the effects of chronic disease comorbidities
      on health outcomes. Understanding these effects will guide the development of
      health care programs that address unique care needs of different patient
      subpopulations. Additionally, these insights bring new attention to individuals
      at high risk for readmission based on chronic disease comorbidities, allowing for
      more personalized attention and prioritization of care. Conclusion: Multi
      hypothesis causal analysis, a new methodological tool, generates meaningful
      insights from health care claims data, guiding the design of care and
      intervention programs.

PMID- 29202189
TI  - Effects of Pesticides on the Survival of Rove Beetle (Coleoptera: Staphylinidae)
      and Insidious Flower Bug (Hemiptera: Anthocoridae) Adults.
AB  - This study determined the direct, indirect, or both effects of pesticides on the
      rove beetle, Dalotia coriaria (Kraatz) (Coleoptera: Staphylinidae), and the
      insidious flower bug, Orius insidiosus (Say) (Hemiptera: Anthocoridae). The
      pesticides evaluated were Capsicum oleoresin extract, garlic oil, and soybean
      oil; cyantraniliprole; flupyradifurone; GS-omega/kappa-Hxtx-Hv1; Isaria
      fumosorosea; tolfenpyrad; pyrethrins; and spinosad. One experiment was conducted
      in a greenhouse with rove beetle adults exposed to growing medium applications of
      cyantraniliprole. The number of live and dead rove beetle adults was determined
      after 10 d. Four additional experiments were conducted under laboratory
      conditions. Rove beetle or insidious flower bug adults were individually placed
      into Petri dishes with filter paper treated with the pesticides. After 24, 48,
      72, and 96 h, the number of live and dead adults of both natural enemies was
      recorded. GS-omega/kappa-Hxtx-Hv1 (VST-006340LC); tolfenpyrad; Capsicum oleoresin
      extract, garlic oil, and soybean oil (Captiva); and Isaria fumosorosea were not
      directly harmful to O. insidiosus (80-100% adult survival). Likewise, the
      pesticides such as tolfenpyrad, Captiva, and I. fumosoroea were not directly
      harmful to D. coriaria (80-100% adult survival). D. coriaria was more sensitive
      to VST-006340LC (40% survival) than O. insidiosus (100% survival), whereas O.
      insidiosus was more sensitive to flupyradifurone (0% survival) than D. coriaria
      (80% and 40% survival for both rates tested, respectively). The pesticides
      pyrethrins, spinosad, flupyradifurone, and combinations of tolfenpyrad and
      Captiva were directly harmful (<50% adult survival) to both natural enemies.
      However, none of the pesticides tested affected the ability of O. insidiosus
      adults to feed on western flower thrips adults.

PMID- 29202190
TI  - Lack of Truncated IFITM3 Transcripts in Cells Homozygous for the rs12252-C
      Variant That is Associated With Severe Influenza Infection.
AB  - Interferon-induced transmembrane 3 (IFITM3) is known to restrict the entry of a
      range of enveloped viruses. The single nucleotide polymorphism rs12252-C within
      IFITM3 has been shown to be associated with severe influenza A virus infection.
      It has been suggested that rs12252-C results in expression of a truncated IFITM3
      protein lacking the first 21 amino acids. By performing high-throughput RNA
      sequencing on primary dendritic cells and peripheral blood mononuclear cells
      isolated from pandemic H1N1 influenza and human immunodeficiency virus-1 (HIV-1)
      infected patients we show that full-length IFITM3 mRNA is dominantly expressed
      (>99%) across all rs12252 genotypes. Full-length IFITM3 protein can be detected
      in all genotypes.

PMID- 29202191
TI  - Effect of Fungal Species on the Development and Reproductive Traits of the Fungal
      Feeding Mite Rhizoglyphus robini (Astigmata: Acaridae).
AB  - The bulb mite, Rhizoglyphus robini (Claparede; Astigmata: Acaridae), is a
      cosmopolitan pest with a broad host range, including commercially grown edible
      fungi in China. In this study, we recorded the development and reproductive
      traits of the bulb mite reared on four mushroom species: Agaricus bisporus Lange,
      Pleurotus ostreatus Kumm, Pleurotus pulmonarius (Fr.) Quel., and Lentinula edodes
      (Berk.) Pegler at six constant temperatures ranging from 15 to 31 degrees C and
      80% RH. Developmental time for the immature stages was significantly affected by
      fungal species, ranging from 9.45 +/- 1.83 d (reared on L. edodes at 31 degrees
      C) to 26.39 +/- 2.10 d (reared on A. bisporus at 15 degrees C). Edible fungi
      species significantly affected intrinsic rates of natural increase (rm) at 31
      degrees C (varied from 0.23 to 0.28) as did the mite's net reproductive rates
      (R0) (103.78, 90.43, 70.77, and 97.45, respectively). Longevity, fecundity and
      female lifespan were dependent on host fungi.

PMID- 29202192
TI  - Enhancing nutrition with pulses: defining a recommended serving size for adults.
AB  - Pulses, defined as dry-harvested leguminous crops, include several varieties of
      beans, peas, lentils, and chickpeas. There is no consensus around a recommended
      serving size of pulses within a balanced diet, which prevents the development of
      transregional strategies that rely on consistent messaging to drive increases in
      consumption. The purpose of this review is to define and disseminate an
      appropriate target for a minimum serving size of pulses on any given day that can
      be used in international or collaborative strategies to promote the consumption
      of pulses. Relevant data were reviewed to examine dietary guidelines across
      jurisdictions, determine consumption levels of pulses across the globe, evaluate
      the nutritional composition of pulses in the context of dietary nutrient
      insufficiency, and assess the impact of pulses on dietary quality. Across a
      variety of pulses, 100 g of cooked pulses aligned with most regional serving
      sizes for pulses and provides significant levels of nutrients that are
      underconsumed by specific age-sex groups. Moreover, 100 g of pulses provides a
      number of nutrients that qualify for nutrient content claims under regional
      regulatory frameworks. The data demonstrate that 100 g or 125 mL (0.5 metric cup)
      of cooked pulses is a reasonable target for aligning strategies that promote the
      dietary and nutritional attributes of these legumes.

PMID- 29202193
TI  - SeekDeep: single-base resolution de novo clustering for amplicon deep sequencing.
AB  - PCR amplicon deep sequencing continues to transform the investigation of genetic
      diversity in viral, bacterial, and eukaryotic populations. In eukaryotic
      populations such as Plasmodium falciparum infections, it is important to
      discriminate sequences differing by a single nucleotide polymorphism. In
      bacterial populations, single-base resolution can provide improved resolution
      towards species and strains. Here, we introduce the SeekDeep suite built around
      the qluster algorithm, which is capable of accurately building de novo clusters
      representing true, biological local haplotypes differing by just a single base.
      It outperforms current software, particularly at low frequencies and at low input
      read depths, whether resolving single-base differences or traditional OTUs.
      SeekDeep is open source and works with all major sequencing technologies, making
      it broadly useful in a wide variety of applications of amplicon deep sequencing
      to extract accurate and maximal biologic information.

PMID- 29202194
TI  - Insights into the structural and mechanistic basis of multifunctional S.
      cerevisiae Pif1p helicase.
AB  - The Saccharomyces cerevisiae Pif1 protein (ScPif1p) is the prototypical member of
      the Pif1 family of DNA helicases. ScPif1p is involved in the maintenance of
      mitochondrial, ribosomal and telomeric DNA and suppresses genome instability at G
      quadruplex motifs. Here, we report the crystal structures of a truncated ScPif1p
      (ScPif1p237-780) in complex with different ssDNAs. Our results have revealed that
      a yeast-specific insertion domain protruding from the 2B domain folds as a bundle
      bearing an alpha-helix, alpha16. The alpha16 helix regulates the helicase
      activities of ScPif1p through interactions with the previously identified loop3.
      Furthermore, a biologically relevant dimeric structure has been identified, which
      can be further specifically stabilized by G-quadruplex DNA. Basing on structural
      analyses and mutational studies with DNA binding and unwinding assays, a
      potential G-quadruplex DNA binding site in ScPif1p monomers is suggested. Our
      results also show that ScPif1p uses the Q-motif to preferentially hydrolyze ATP,
      and a G-rich tract is preferentially recognized by more residues, consistent with
      previous biochemical observations. These findings provide a structural and
      mechanistic basis for understanding the multifunctional ScPif1p.

PMID- 29202196
TI  - Effects of DLC1 Deficiency on Endothelial Cell Contact Growth Inhibition and
      Angiosarcoma Progression.
AB  - Background: Deleted in Liver Cancer 1 (DLC1) is a tumor suppressor gene
      frequently deleted in cancer. However, DLC1 is not known to be deleted in
      angiosarcoma, an aggressive malignancy of endothelial cell derivation.
      Additionally, the physiologic functions of DLC1 protein in endothelial cells are
      poorly defined. Methods: We investigated the effects of shRNA-induced DLC1
      depletion in endothelial cells. Cell growth was measured by 3H thymidine
      incorporation, IncuCyte imaging, and population doublings; cell death by cell
      cycle analysis; gene expression by Affimetrix arrays and quantitative polymerase
      chain reaction; NF-kappaB activity by reporter assays; and protein levels by
      immunoblotting and immunofluorescence staining. We tested Tanespimycin/17-AAG and
      Fasudil treatment in groups of nine to 10 mice bearing ISOS-1 angiosarcoma. All
      statistical tests were two-sided. Results: We discovered that DLC1 is a critical
      regulator of cell contact inhibition of proliferation in endothelial cells,
      promoting statistically significant (P < .001) cell death when cells are
      confluent (mean [SD] % viability: control DLC1 = 15.6 [19.3]; shDLC1 = 73.4
      [13.1]). This prosurvival phenotype of DLC1-depleted confluent endothelial cells
      is attributable to a statistically significant and sustained increase of NF
      kappaB activity (day 5, P = .001; day 8, P = .03) associated with increased tumor
      necrosis factor alpha-induced protein 3 (TNFAIP3/A20) signaling. Consistently, we
      found that DLC1 is statistically significantly reduced (P < .001 in 5 of 6) and
      TNFAIP3/A20 is statistically significantly increased (P < .001 in 2 of 3 and P =
      0.02 in 1 of 3) in human angiosarcoma compared with normal adjacent endothelium.
      Treatment with the NF-kappaB inhibitor Tanespimycin/17-AAG statistically
      significantly reduced angiosarcoma tumor growth in mice (treatment tumor weight
      vs control, 0.50 [0.19] g vs 0.91 [0.21] g, P = .001 experiment 1; 0.66 [0.26] g
      vs 1.10 [0.31] g, P = .01 experiment 2). Conclusions: These results identify DLC1
      as a previously unrecognized regulator of endothelial cell contact inhibition of
      proliferation that is depleted in angiosarcoma and support NF-kappaB targeting
      for the treatment of angiosarcoma where DLC1 is lost.

PMID- 29202197
TI  - Unfertilized ovary pushes wheat flower open for cross-pollination.
AB  - Bread wheat is strongly autogamous; however, an opportunity for outcrossing
      occurs when self-pollination fails and florets open. The first phase of floret
      opening at anthesis is short and induced by lodicule turgidity. Some wheat
      florets re-open post-anthesis for several days, known as the 'second opening',
      for which the underlying mechanisms are largely unknown. We performed detailed
      physiological, anatomical, and histological investigations to understand the
      biological basis of the flower opening process. Wheat florets were observed open
      when the ovary was unfertilized. Unfertilized ovaries significantly increased in
      radial size post-anthesis, pushing the lemma and palea apart to open the florets.
      The absence of fertile pollen was not directly linked to this, but anther
      filament elongation coincided with initiation of ovary swelling. The pericarp of
      unfertilized ovaries did not undergo degeneration as normally seen in developing
      grains, instead pericarp cells remained intact and enlarged, leading to increased
      ovary radial size. This is a novel role for the ovary pericarp in wheat flower
      opening, and the knowledge is useful for facilitating cross-pollination in hybrid
      breeding. Ovary swelling may represent a survival mechanism in autogamous cereals
      such as wheat and barley, ensuring seed set in the absence of self-fertilization
      and increasing genetic diversity through cross-pollination.

PMID- 29202198
TI  - Adverse effects of gluten ingestion and advantages of gluten withdrawal in
      nonceliac autoimmune disease.
AB  - In light of the coincident surge in overall gluten intake and the incidence of
      autoimmune diseases, the possible biological adverse effects of gluten were
      explored. PubMed, MEDLINE, and the Cochrane Library databases were screened for
      reports published between 1964 and 2016 regarding the adverse effects of gluten
      as well as the effects of a gluten-free diet on autoimmune diseases. In vitro and
      in vivo studies describing gluten intake in animal models or cell lines and
      gluten-free diets in human autoimmune diseases were reviewed. Multiple
      detrimental aspects of gluten affect human health, including gluten-dependent
      digestive and extradigestive manifestations mediated by potentially immunological
      or toxic reactions that induce gastrointestinal inadequacy. Gluten affects the
      microbiome and increases intestinal permeability. It boosts oxidative stress and
      affects epigenetic behavior. It is also immunogenic, cytotoxic, and
      proinflammatory. Gluten intake increases apoptosis and decreases cell viability
      and differentiation. In certain nonceliac autoimmune diseases, gluten-free diets
      may help curtail the adverse effects of gluten. Additional in vivo studies are
      needed to unravel the puzzle of gluten effects in humans and to explore the
      potential beneficial effects of gluten-free diets in autoimmune diseases.

PMID- 29202195
TI  - Mechanisms of bacterial DNA replication restart.
AB  - Multi-protein DNA replication complexes called replisomes perform the essential
      process of copying cellular genetic information prior to cell division. Under
      ideal conditions, replisomes dissociate only after the entire genome has been
      duplicated. However, DNA replication rarely occurs without interruptions that can
      dislodge replisomes from DNA. Such events produce incompletely replicated
      chromosomes that, if left unrepaired, prevent the segregation of full genomes to
      daughter cells. To mitigate this threat, cells have evolved 'DNA replication
      restart' pathways that have been best defined in bacteria. Replication restart
      requires recognition and remodeling of abandoned replication forks by DNA
      replication restart proteins followed by reloading of the replicative DNA
      helicase, which subsequently directs assembly of the remaining replisome
      subunits. This review summarizes our current understanding of the mechanisms
      underlying replication restart and the proteins that drive the process in
      Escherichia coli (PriA, PriB, PriC and DnaT).

PMID- 29202199
TI  - Drosophila suzukii (Diptera: Drosophilidae) Contributes to the Development of
      Sour Rot in Grape.
AB  - This research aimed to more clearly describe the interactions of Drosophila
      suzukii (Matsumura; Diptera: Drosophilidae) with microorganisms that may
      contribute to spoilage or quality loss of wine grapes during harvest. Experiments
      were conducted in controlled laboratory experiments and under field conditions to
      determine these effects. Laboratory trials determined the role of insect contact
      and oviposition to vector spoilage bacteria onto wine grapes. In the field, the
      roles of key organoleptic parameters in grape fruit ripening were assessed to
      determine their relative contribution to oviposition potential as fruit ripened.
      Finally, field trials determined the relationships of egg and larval infestation
      to sour rot levels. Non-ovipositional trials indicated elevated levels of
      microbiota when D. suzukii was present. D. suzukii oviposition exponentially
      increased the concentration of acetic acid bacteria. Both incised and sound
      berries showed a significant increase in concentrations of acetic acid bacteria
      exposed to D. suzukii. Volatile acidity was higher in treatments infested with D.
      suzukii. Fruit with only eggs did not develop a significant increase of volatile
      acidity. Larva-infested grape berries in 9.5% of samples developed higher
      volatile acidity after 14 d. Sound grape berries were less susceptible to the
      development of microbiota associated with sour rot and spoilage. D. suzukii
      oviposition and larval development increase risk of spoilage bacteria vectored by
      D. suzukii adults. Acetic acid bacteria induced fermentation and produced several
      volatile compounds contributing to spoilage. Spoilage bacteria may create a
      positive feedback loop that attracts both D. suzukii and other drosophilids,
      which may contribute to additional spoilage.

PMID- 29202201
TI  - Prevalence and Seasonality of Fleas Associated With California Ground Squirrels
      and the Potential Risk of Tularemia in an Outdoor Non-Human Primate Research
      Facility.
AB  - Ectoparasites at primate research centers may be difficult to control, e.g.
      without exposing non-human primates (NHPs) to toxicants, but their impact on NHP
      health is poorly understood. In 2010, there was an epizootic of tularemia at the
      California National Primate Research Center (CNPRC) in Yolo County, California
      that resulted in 20 confirmed and suspect clinical cases in outdoors housed
      rhesus macaques (Macaca mulatta [Zimmermann]) and a 53% seroprevalence in the
      southern section of the colony. We studied ectoparasite burdens at the CNPRC in
      order to understand possible conditions at the time of the epizootic and provide
      data for the management of ectoparasites for the future. In 2015, we recorded 52
      California ground squirrel (Otospermophilus beecheyi [Richardson]) burrow systems
      in the southern colony and collected 560 fleas. The largest number of fleas (n =
      184) was collected in October and the most common species were Hoplopsyllus
      anomalus (Baker) (n = 331), Oropsylla montana (Baker) (n = 158), Echidnophaga
      gallinacea (Westwood) (n = 60), and Ctenocephalides felis (Bouche) (n = 11), all
      of which are opportunistically anthropophilic. Free, non-host-associated fleas
      included 12 H. anomalus, 9 C. felis, 6 O. Montana, and 1 E. gallinacea. We
      collected 1 H. anomalus from a rhesus macaque. Our results suggest a high
      potential for the rapid spread of zoonotic infectious diseases via flea
      transmission in primate facilities with ground squirrels and that flea control
      measures should be given a high priority.

PMID- 29202200
TI  - Alternative start and termination sites of transcription drive most transcript
      isoform differences across human tissues.
AB  - Most human genes generate multiple transcript isoforms. The differential
      expression of these isoforms can help specify cell types. Diverse transcript
      isoforms arise from the use of alternative transcription start sites,
      polyadenylation sites and splice sites; however, the relative contribution of
      these processes to isoform diversity in normal human physiology is unclear. To
      address this question, we investigated cell type-dependent differences in exon
      usage of over 18 000 protein-coding genes in 23 cell types from 798 samples of
      the Genotype-Tissue Expression Project. We found that about half of the expressed
      genes displayed tissue-dependent transcript isoforms. Alternative transcription
      start and termination sites, rather than alternative splicing, accounted for the
      majority of tissue-dependent exon usage. We confirmed the widespread tissue
      dependent use of alternative transcription start sites in a second, independent
      dataset, Cap Analysis of Gene Expression data from the FANTOM consortium.
      Moreover, our results indicate that most tissue-dependent splicing involves
      untranslated exons and therefore may not increase proteome complexity. Thus,
      alternative transcription start and termination sites are the principal drivers
      of transcript isoform diversity across tissues, and may underlie the majority of
      cell type specific proteomes and functions.

PMID- 29202202
TI  - Phlebotomus halepensis (Diptera: Psychodidae) Vectorial Capacity in Afyon and
      Nigde Province, Turkey.
AB  - Leishmaniasis is a one of the vector-borne diseases and has two clinical forms in
      Turkey: cutaneous and visceral. The aim of this study was to determine the sand
      fly fauna in Afyon and Nigde provinces where endemic foci of cutaneous
      leishmaniasis (CL) in Turkey. In Afyon, 2,259 sand flies were collected in 73
      locations in August 2009 and August 2010, using CDC light traps. In total, eight
      Phlebotomus species were identified; Phlebotomus halepensis (47.41%), Phlebotomus
      papatasi (31.42%), Phlebotomus neglectus/syriacus (9.38%), Phlebotomus balcanicus
      (7.48%), Phlebotomus simici (2.12%), Phlebotomus perfiliewi (1.90%), Phlebotomus
      sergenti (0.08%), Phlebotomus similis (0.13%), and Sergentomyia dentata (0.04%).
      A total of 418 sand fly specimens were caught by CDC light traps in 40 stations
      in Nigde in September 2009 and September 2010. In total, seven Phlebotomus
      species were identified; P. halepensis (74.16%), P. simici (13.87%), P. papatasi
      (3.82%), P. neglectus/syriacus (2.87%), P. balcanicus (2.63%), P. sergenti
      (2.39%), and Phlebotomus tobbi (0.23%). Collected sand flies were examined by
      microscope, and no promastigotes were found in their midguts. We categorized and
      pooled female specimens (1,031 females, 73 pools of 2-33 individuals). Leishmania
      species-specific ITS1 real-time PCR assay was performed for detection and
      identification of parasites. We detected 6 of the 73 pools with Leishmania
      tropica (Ross, 1903), (Trypanosomatidae). In conclusion, P. halepensis was found
      to be dominant species in both areas. We are in opinion that our findings support
      P. halepensis vectorial role for L. tropica in nature and it could be responsible
      for the transmission of L. tropica in these endemic areas.

PMID- 29202203
TI  - User needs analysis and usability assessment of DataMed - a biomedical data
      discovery index.
AB  - Objective: To present user needs and usability evaluations of DataMed, a Data
      Discovery Index (DDI) that allows searching for biomedical data from multiple
      sources. Materials and Methods: We conducted 2 phases of user studies. Phase 1
      was a user needs analysis conducted before the development of DataMed, consisting
      of interviews with researchers. Phase 2 involved iterative usability evaluations
      of DataMed prototypes. We analyzed data qualitatively to document researchers'
      information and user interface needs. Results: Biomedical researchers'
      information needs in data discovery are complex, multidimensional, and shaped by
      their context, domain knowledge, and technical experience. User needs analyses
      validate the need for a DDI, while usability evaluations of DataMed show that
      even though aggregating metadata into a common search engine and applying
      traditional information retrieval tools are promising first steps, there remain
      challenges for DataMed due to incomplete metadata and the complexity of data
      discovery. Discussion: Biomedical data poses distinct problems for search when
      compared to websites or publications. Making data available is not enough to
      facilitate biomedical data discovery: new retrieval techniques and user
      interfaces are necessary for dataset exploration. Consistent, complete, and high
      quality metadata are vital to enable this process. Conclusion: While available
      data and researchers' information needs are complex and heterogeneous, a
      successful DDI must meet those needs and fit into the processes of biomedical
      researchers. Research directions include formalizing researchers' information
      needs, standardizing overviews of data to facilitate relevance judgments,
      implementing user interfaces for concept-based searching, and developing
      evaluation methods for open-ended discovery systems such as DDIs.

PMID- 29202204
TI  - Cost-effectiveness of yoga for managing musculoskeletal conditions in the
      workplace.
AB  - Background: Back pain and musculoskeletal conditions negatively affect the health
      related quality of life (HRQL) of employees and generate substantial costs to
      employers. Aims: To assess the cost-effectiveness of yoga for managing
      musculoskeletal conditions. Methods: A randomized controlled trial evaluated an 8
      week yoga programme, with a 6-month follow-up, for National Health Service (NHS)
      employees. Effectiveness in managing musculoskeletal conditions was assessed
      using repeated-measures generalized linear modelling for the Roland-Morris
      Disability Questionnaire (RDQ) and the Keele STarT Back Screening Tool. Cost
      effectiveness was determined using area-under-the-curve linear regression for
      assessing HRQL from healthcare and societal perspectives. The incremental cost
      per quality-adjusted life year (QALY) was also calculated. Sickness absence was
      measured using electronic staff records at 6 months. Results: There were 151
      participants. At 6 months, mean differences between groups favouring yoga were
      observed for RDQ [-0.63 (95% CI, -1.78, 0.48)], Keele STarT [-0.28 (95% CI, 
      0.97, 0.07)] and HRQL (0.016 QALY gain). From a healthcare perspective, yoga
      yielded an incremental cost-effectiveness ratio of L2103 per QALY. Given a
      willingness to pay for an additional QALY of L20 000, the probability of yoga
      being cost-effective was 95%. From a societal perspective, yoga was the dominant
      treatment compared with usual care. At 6 months, electronic staff records showed
      that yoga participants missed a total of 2 working days due to musculoskeletal
      conditions compared with 43 days for usual care participants. Conclusions: Yoga
      for NHS employees may enhance HRQL, reduce disability associated with back pain,
      lower sickness absence due to musculoskeletal conditions and is likely to be cost
      effective.

PMID- 29202205
TI  - 3D-MICE: integration of cross-sectional and longitudinal imputation for multi
      analyte longitudinal clinical data.
AB  - Objective: A key challenge in clinical data mining is that most clinical datasets
      contain missing data. Since many commonly used machine learning algorithms
      require complete datasets (no missing data), clinical analytic approaches often
      entail an imputation procedure to "fill in" missing data. However, although most
      clinical datasets contain a temporal component, most commonly used imputation
      methods do not adequately accommodate longitudinal time-based data. We sought to
      develop a new imputation algorithm, 3-dimensional multiple imputation with
      chained equations (3D-MICE), that can perform accurate imputation of missing
      clinical time series data. Methods: We extracted clinical laboratory test results
      for 13 commonly measured analytes (clinical laboratory tests). We imputed missing
      test results for the 13 analytes using 3 imputation methods: multiple imputation
      with chained equations (MICE), Gaussian process (GP), and 3D-MICE. 3D-MICE
      utilizes both MICE and GP imputation to integrate cross-sectional and
      longitudinal information. To evaluate imputation method performance, we randomly
      masked selected test results and imputed these masked results alongside results
      missing from our original data. We compared predicted results to measured results
      for masked data points. Results: 3D-MICE performed significantly better than MICE
      and GP-based imputation in a composite of all 13 analytes, predicting missing
      results with a normalized root-mean-square error of 0.342, compared to 0.373 for
      MICE alone and 0.358 for GP alone. Conclusions: 3D-MICE offers a novel and
      practical approach to imputing clinical laboratory time series data. 3D-MICE may
      provide an additional tool for use as a foundation in clinical predictive
      analytics and intelligent clinical decision support.

PMID- 29202206
TI  - Ehrlichia and Anaplasma Infections: Serological Evidence and Tick Surveillance in
      Peninsular Malaysia.
AB  - Little information is available on human anaplasmosis and ehrlichiosis in
      Southeast Asia despite increasing reports of the detection of Anaplasma spp. and
      Ehrlichia spp. in the ticks. We report herein the serological findings against
      the tick-borne pathogens in a group of animal farm workers (n = 87) and
      indigenous people (n = 102) in Peninsular Malaysia. IgG antibodies against
      Ehrlichia chaffeensis were detected from 29.9% and 34.3% of farm workers and
      indigenous people, respectively, using commercial indirect immunofluorescence
      assays. Comparatively, only 6.9% of the indigenous people but none of the animal
      farm workers were seropositive to Anaplasma phagocytophilum. A polymerase chain
      reaction (PCR) assay targeting the 16S rRNA gene of Anaplasmataceae was used to
      identify Anaplastamataceae in ticks collected from various locations adjacent to
      the areas where the serological survey was conducted. In this study, a total of
      61.5% of ticks infesting farm animals, 37.5% of ticks infesting peri-domestic
      animals in rural villages, 27.3% of ticks collected from wildlife animals, and
      29.1% of questing ticks collected from forest vegetation were positive for
      Anaplasmataceae DNA. Sequence analyses of 16S rRNA gene region (238 bp) provide
      the identification for Anaplasma marginale, Anaplasma bovis, Anaplasma platys, A.
      phagocytophilum, and Anaplasma spp. closely related to Candidatus Cryptoplasma
      californiense in ticks. E. chaffeensis DNA was not detected from any ticks,
      instead, Ehrlichia sp. strain EBm52, Ehrlichia mineirensis and Candidatus
      Ehrlichia shimanensis are the only Ehrlichia sp. identified from cattle ticks in
      this study. Further investigation is required to ascertain the occurrence of
      zoonotic transmission of Ehrlichia and Anaplasma infections in Peninsular
      Malaysia.

PMID- 29202207
TI  - Tecarfarin: A Novel Vitamin K Antagonist.

PMID- 29202208
TI  - Therapeutic Shifts in the Management of Cancer-Associated Thrombosis.

PMID- 29202209
TI  - Dabigatran versus Warfarin for Acute Venous Thromboembolism in Elderly or
      Impaired Renal Function Patients: Pooled Analysis of RE-COVER and RE-COVER II.
AB  - Management of acute venous thromboembolism (VTE) with anticoagulants in elderly
      patients and those with chronic kidney disease poses special challenges. The RE
      COVER and RE-COVER II trials showed that dabigatran 150 mg twice daily was as
      effective as warfarin over 6 months in preventing recurrent VTE, with a lower
      bleeding risk. We now assess the effects of old age and renal impairment (RI) on
      pooled trial outcomes in 5,107 patients: 4,504 aged <75 years and 603 aged >=75
      years. The primary efficacy outcome was symptomatic VTE/VTE-related death. Safety
      outcomes were centrally adjudicated major bleeding events (MBEs), MBEs or
      clinically relevant non-major bleeding events (MBEs/CRBEs) and any bleeds.
      Baseline renal function was categorized as normal, mild RI or moderate RI. A
      total of 3,698 had normal renal function and 1,100 and 237 had mild and moderate
      RI, respectively (23 patients with severe RI and 49 with missing creatinine
      clearance data were not included). For dabigatran, VTE/VTE-related death
      decreased from 3.1% (normal renal function) to 1.9% for mild RI and to 0.0% for
      moderate RI. For warfarin, the event rates were 2.6, 1.6 and 4.1%, respectively.
      Overall, major bleeding increased with increasing RI (p = 0.0037) and with age (p
      = 0.4350), with no apparent difference between the dabigatran and warfarin
      patients. Dabigatran shows better efficacy than warfarin in RI and in the elderly
      patients, probably because of an increase in the concentration of dabigatran.
      However, bleeding risk increases with both dabigatran and warfarin in the
      presence of RI.

PMID- 29202210
TI  - Differential Effects on Haemostatic Markers by Metformin and the Contraceptive
      Pill: A Randomized Comparative Trial in PCOS.
AB  - Background Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive
      aged women with increased risks of cardiovascular disease and venous
      thromboembolic disease, related to metabolic and hormonal features, obesity and
      an apparent hypofibrinolytic state, possibly exacerbated by current PCOS
      treatments. Objective To investigate and compare haemostatic impacts of common
      pharmacological treatments and explore relationships with hormonal and metabolic
      variables in PCOS. Patients/Methods This mechanistic sub-study using biobanked
      samples from a 6-month randomized comparative trial of pharmacological treatments
      assessed pro- and anti-thrombotic markers and overall haemostatic activity.
      Overweight women of mean age 33.9 +/- 6.7 years and mean BMI (body mass index) of
      36.5 +/- 7.0 kg/m2 with PCOS (n = 60) were randomized to either metformin, higher
      dose oral contraceptive pill (OCP) or low-dose OCP + spironolactone (OCP + S).
      Primary outcome measures included changes in plasminogen activator inhibitor 1
      (PAI-1), asymmetric dimethylarginine (ADMA), prothrombin fragments 1 and 2 (PF1
      and 2), plasminogen, tissue plasminogen activator (tPA), thrombin activatable
      fibrinolysis inhibitor (TAFI) and thrombin generation (TG). Results PAI-1
      activity fell in all groups, ADMA fell in higher-dose OCP, PF1 and 2 increased
      with metformin and higher-dose OCP, TG rose and tPA fell in both OCP groups,
      plasminogen increased in all and TAFI increased after higher-dose OCP. Conclusion
      Endothelial function (primary haemostasis) improved with higher dose with some
      improvement in low-dose OCP + S and metformin. Aberrant coagulation was noted in
      both OCP groups, but not with metformin. Fibrinolysis was reduced with higher
      dose OCP. Our work suggests an additional dimension of treatment (haemostatic
      system effects) that favours metformin treatment over the OCP in PCOS.

PMID- 29202211
TI  - Acute Haemarthrosis in the Haemophilia A Rat Generates a Local and Systemic
      Proinflammatory Response.
AB  - Background Replacement therapy with coagulation factor VIII (FVIII) concurrent
      with bleeds (on-demand) in haemophilia A (HA) patients has been hypothesized to
      increase the risk for antidrug antibodies (inhibitors). A danger signal
      environment, characterized by tissue damage and inflammation at the site of a
      bleed, is thought to contribute to the anti-FVIII response. The nature of this
      inflammatory reaction is, however, not fully known, and new insights will be
      valuable for both managing inhibitors and understanding arthropathy development.
      Objective To characterize the inflammatory response, locally and systemically,
      during the first 24 hours following a joint bleed in the HA rat. Methods HA rats
      received a needle-induced knee joint bleed (n = 83) or a sham procedure (n = 41).
      Blood samples were collected at selected time points from 0 to 24 hours post
      injury/sham. Synovial fluid, intra-articular knee tissue and popliteal lymph
      nodes were collected at 24 hours. Cytokine/chemokine concentrations and gene
      expression were measured. Results Gene expression analysis revealed a rapid
      inflammatory response in the injured knees, accompanied by significantly
      increased levels of specific gene products in the synovial fluid; IL-1beta,
      TNFalpha, KC/GRO, IL-6, Eotaxin, MCP-1, MCP-3, MIP-1alpha, MIP-2, RANTES, A2M and
      AGP. Plasma analysis demonstrated significantly increased systemic levels of
      KC/GRO and IL-6 in injured rats already after 5 to 6 hours. Conclusion A rapid
      proinflammatory response, locally and systemically, characteristic of innate
      immunity, was demonstrated. Results reveal a more comprehensive inflammatory
      picture than previously shown, with resemblance to human haemophilic arthropathy,
      and with unique correlation between gene expression level, synovial concentration
      and plasma concentration in individual rats.

PMID- 29202212
TI  - Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through
      Alveolar Macrophages in a Rat Model of Acute Lung Injury.
AB  - Objective Alveolar macrophages play a key role in the development and resolution
      of acute respiratory distress syndrome (ARDS), modulating the inflammatory
      response and the coagulation cascade in lungs. Anti-coagulants may be helpful in
      the treatment of ARDS. This study investigated the effects of nebulized heparin
      on the role of alveolar macrophages in limiting lung coagulation and inflammatory
      response in an animal model of acute lung injury (ALI). Methods Rats were
      randomized to four experimental groups. In three groups, ALI was induced by
      intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized
      at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8
      hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes
      before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received
      nebulized saline 4 and 8 hours after injury. The control group received only
      saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue,
      bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF
      were analysed. Results LPS increased protein concentration, oedema and
      neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung
      tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI
      through decreasing procoagulant (tissue factor, thrombin-anti-thrombin complexes,
      fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis
      factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced
      expression of procoagulant genes and the effectors of transforming growth factor
      beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre
      treatment resulted in more pronounced attenuation. Conclusion Nebulized heparin
      reduced pulmonary coagulopathy and inflammation without producing systemic
      bleeding, partly by modulating alveolar macrophages.

PMID- 29202215
TI  - Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Dabigatran
      Etexilate Oral Liquid Formulation in Infants with Venous Thromboembolism.
AB  - Venous thromboembolism (VTE) is more frequent in infants than in older children.
      Treatment guidelines in children are adapted from adult VTE data, but do not
      currently include direct oral anticoagulant use. Dabigatran etexilate (DE) use in
      the paediatric population with VTE therefore requires verification. We
      investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationship, safety and
      tolerability of DE oral liquid formulation (OLF) in infants with VTE (aged < 12
      months) who had completed standard anticoagulant treatment in an open-label,
      phase IIa study. Patients received a single-dose of DE OLF (based on an age- and
      weight-adjusted nomogram) yielding an exposure comparable to 150 mg in adults.
      The PK end point was plasma concentration of total dabigatran; PD end points
      included activated partial thromboplastin time (aPTT), ecarin clotting time (ECT)
      and diluted thrombin time (dTT). Safety end points included incidence of all
      bleeding and other adverse events (AEs). Ten patients were screened; eight
      entered the study (age range, 41-169 days). The geometric mean (gMean) total
      dabigatran plasma concentrations 2 hours post-dose (around peak concentrations)
      were 120 ng/mL with a geometric coefficient of variation (gCV) of 62.1%. The
      gMean at 12 hours post-dosing was 60.4 ng/mL (gCV 30%). PK/PD relationship was
      linear for ECT and dTT (R2 = 0.858 and 0.920, respectively), while total
      dabigatran concentration and aPTT showed a non-linear correlation. There were no
      deaths, treatment discontinuations or treatment-related AEs. In conclusion, DE
      was well tolerated without any treatment-related AEs in infants. The observed
      PK/PD relationships were comparable with the established profile in older
      patients with VTE.

PMID- 29202217
TI  - DNA Modulates the Interaction of Genetically Engineered DNA-Binding Proteins and
      Gold Nanoparticles: Diagnosis of High-Risk HPV Infection.
AB  - Gene detection has an important role in diagnosing several serious diseases and
      genetic defects in modern clinical medicine. Herein, we report a fast and
      convenient gene detection method based on the modulation of the interaction
      between a heat-resistant double-stranded DNA (dsDNA)-binding protein (Sso7d) and
      gold nanoparticles (Au NPs). We prepared a recombinant Cys-Sso7d, which is Sso7d
      with an extra cysteine (Cys) residue in the N-terminus, through protein
      engineering to control the interaction between Sso7d and Au NPs. Cys-Sso7d
      exhibited a stronger affinity for Au NPs and more easily induced the aggregation
      of Au NPs than Sso7d. In addition, Cys-Sso7d retained its ability to bind with
      dsDNA. The aggregation of Au NPs induced by Cys-Sso7d was diminished in the
      presence of dsDNA, which could be utilized as a transduction mechanism for the
      detection of the polymerase chain reaction (PCR) products of human papillomavirus
      (HPV) gene fragments (HPV types 16 and 18). The Cys-Sso7d/Au NP probe could
      detect as few as 1 copy of the HPV gene. The sensitivity and specificity of the
      Cys-Sso7d/Au NP probe for Pap smear clinical specimens (n = 52) for HPV 16 and
      HPV 18 detection were 85.7%/100.0% and 85.7%/91.7%, respectively. Our results
      demonstrate that the Cys-Sso7d/Au NP probe can be used to diagnose high-risk HPV
      types in Pap smear samples with high sensitivity, specificity, and accuracy.

PMID- 29202216
TI  - Type II-C CRISPR-Cas9 Biology, Mechanism, and Application.
AB  - Genome editing technologies have been revolutionized by the discovery of
      prokaryotic RNA-guided defense system called CRISPR-Cas. Cas9, a single effector
      protein found in type II CRISPR systems, has been at the heart of this genome
      editing revolution. Nearly half of the Cas9s discovered so far belong to the type
      II-C subtype but have not been explored extensively. Type II-C CRISPR-Cas systems
      are the simplest of the type II systems, employing only three Cas proteins. Cas9s
      are central players in type II-C systems since they function in multiple steps of
      the CRISPR pathway, including adaptation and interference. Type II-C CRISPR
      systems are found in bacteria and archaea from very diverse environments,
      resulting in Cas9s with unique and potentially useful properties. Certain type II
      C Cas9s possess unusually long PAMs, function in unique conditions (e.g.,
      elevated temperature), and tend to be smaller in size. Here, we review the
      biology, mechanism, and applications of the type II-C CRISPR systems with
      particular emphasis on their Cas9s.

PMID- 29202218
TI  - Biocompatible Amphiphilic Hydrogel-Solid Dimer Particles as Colloidal
      Surfactants.
AB  - Emulsions of two immiscible liquids can slowly coalesce over time when stabilized
      by surfactant molecules. Pickering emulsions stabilized by colloidal particles
      can be much more stable. Here, we fabricate biocompatible amphiphilic dimer
      particles using a hydrogel, a strongly hydrophilic material, and achieve large
      contrast in the wetting properties of the two bulbs, resulting in enhanced
      stabilization of emulsions. We generate monodisperse single emulsions of alginate
      and shellac solution in oil using a flow-focusing microfluidics device. Shellac
      precipitates from water and forms a solid bulb at the periphery of the droplet
      when the emulsion is exposed to acid. Molecular interactions result in
      amphiphilic dimer particles that consist of two joined bulbs: one hydrogel bulb
      of alginate in water and the other hydrophobic bulb of shellac. Alginate in the
      hydrogel compartment can be cross-linked using calcium cations to obtain stable
      particles. Analogous to surfactant molecules at the interface, the resultant
      amphiphilic particles stand at the water/oil interface with the hydrogel bulb
      submerged in water and the hydrophobic bulb in oil and are thus able to stabilize
      both water-in-oil and oil-in-water emulsions, making these amphiphilic hydrogel
      solid particles ideal colloidal surfactants for various applications.

PMID- 29202219
TI  - Direct Single-Molecule Observation of Mode and Geometry of RecA-Mediated Homology
      Search.
AB  - Genomic integrity, when compromised by accrued DNA lesions, is maintained through
      efficient repair via homologous recombination. For this process the ubiquitous
      recombinase A (RecA), and its homologues such as the human Rad51, are of central
      importance, able to align and exchange homologous sequences within single
      stranded and double-stranded DNA in order to swap out defective regions. Here, we
      directly observe the widely debated mechanism of RecA homology searching at a
      single-molecule level using high-speed atomic force microscopy (HS-AFM) in
      combination with tailored DNA origami frames to present the reaction targets in a
      way suitable for AFM-imaging. We show that RecA nucleoprotein filaments move
      along DNA substrates via short-distance facilitated diffusions, or slides,
      interspersed with longer-distance random moves, or hops. Importantly, from the
      specific interaction geometry, we find that the double-stranded substrate DNA
      resides in the secondary DNA binding-site within the RecA nucleoprotein filament
      helical groove during the homology search. This work demonstrates that tailored
      DNA origami, in conjunction with HS-AFM, can be employed to reveal directly
      conformational and geometrical information on dynamic protein-DNA interactions
      which was previously inaccessible at an individual single-molecule level.

PMID- 29202220
TI  - One-Step Treatment of Spin-Orbit Coupling and Electron Correlation in Large
      Active Spaces.
AB  - In this work we demonstrate that the heat bath configuration interaction (HCI)
      and its semistochastic extension can be used to treat relativistic effects and
      electron correlation on an equal footing in large active spaces to calculate the
      low energy spectrum of several systems including halogen group atoms (F, Cl, Br,
      I), coinage atoms (Cu, Au), and the neptunyl(VI) dioxide radical. This work
      demonstrates that despite a significant increase in the size of the Hilbert space
      due to spin symmetry breaking by the spin-orbit coupling terms, HCI retains the
      ability to discard large parts of the low importance Hilbert space to deliver
      converged absolute and relative energies. For instance, by using just over 107
      determinants we get converged excitation energies for Au atom in an active space
      containing (150o,25e) which has over 1030 determinants. We also investigate the
      accuracy of five different two-component relativistic Hamiltonians in which
      different levels of approximations are made in deriving the one-electron and two
      electrons Hamiltonians, ranging from Breit-Pauli (BP) to various flavors of exact
      two-component (X2C) theory. The relative accuracy of the different Hamiltonians
      are compared on systems that range in atomic number from first row atoms to
      actinides.

PMID- 29202221
TI  - Sperm-Hybrid Micromotor for Targeted Drug Delivery.
AB  - A sperm-driven micromotor is presented as a targeted drug delivery system, which
      is appealing to potentially treat diseases in the female reproductive tract. This
      system is demonstrated to be an efficient drug delivery vehicle by first loading
      a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding
      it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the
      sperm cell to deliver the drug locally. The sperm release mechanism is designed
      to liberate the sperm when the biohybrid micromotor hits the tumor walls,
      allowing it to swim into the tumor and deliver the drug through the sperm-cancer
      cell membrane fusion. In our experiments, the sperm cells exhibited a high drug
      encapsulation capability and drug carrying stability, conveniently minimizing 
      toxic side effects and unwanted drug accumulation in healthy tissues. Overall,
      sperm cells are excellent candidates to operate in physiological environments, as
      they neither express pathogenic proteins nor proliferate to form undesirable
      colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a
      biocompatible platform with potential application in gynecological healthcare,
      treating or detecting cancer or other diseases in the female reproductive system.

PMID- 29202222
TI  - Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017-Utility and
      Limitations.
AB  - Pan-Assay Interference Compounds (PAINS) are very familiar to medicinal chemists
      who have spent time fruitlessly trying to optimize these nonprogressible
      compounds. Electronic filters formulated to recognize PAINS can process hundreds
      and thousands of compounds in seconds and are in widespread current use to
      identify PAINS in order to exclude them from further analysis. However, this
      practice is fraught with danger because such black box treatment is simplistic.
      Here, we outline for the first time all necessary considerations for the
      appropriate use of PAINS filters.

PMID- 29202223
TI  - Energy Gaps of Polyradicals from an Effective and Transferable Hamiltonian with
      through-Bond Interactions.
AB  - Current model Hamiltonians and ab initio many-body quantum treatments of pi
      conjugated polyradicals formed from hydrocarbons produce divergent results
      because of numerical complexity and large size of the basis-function set used. We
      propose an alternative, three-term Hamiltonian, to describe these various
      polyradicals that simplifies considerably the computational cost while providing
      a physical interpretation for all three terms and a high degree of model
      universality. The essential feature of this Hamiltonian is a term, not present in
      previous models, describing the three-sited through-bond interaction that governs
      the noninteracting spin-up and spin-down sectors. A computation of the lowest
      energy gaps and spin configurations for the smaller polyradicals demonstrates the
      efficacy of the model and its potential in applications in revealing electrical
      conductivity and ferromagnetism of the more complicated substituted polyradicals.

PMID- 29202224
TI  - Mussel-Inspired Self-Healing Double-Cross-Linked Hydrogels by Controlled
      Combination of Metal Coordination and Covalent Cross-Linking.
AB  - Mussel-inspired hydrogels held together by reversible catecholato-metal
      coordination bonds have recently drawn great attention owing to their attractive
      self-healing, viscoelastic and adhesive properties together with their pH
      responsive nature. A major challenge in these systems is to orchestrate the
      degree of catechol oxidation that occurs under alkaline conditions in air and has
      a great impact on the aforementioned properties because it introduces
      irreversible covalent cross-links to the system, which stiffens the hydrogels but
      consume catechols needed for self-healing. Herein, we present a catechol-based
      hydrogel design that allows for the degree of oxidative covalent cross-linking to
      be controlled. Double cross-linked hydrogels with tunable stiffness are
      constructed by adding the oxidizable catechol analogue, tannic acid, to an
      oxidation-resistant hydrogel construct held together by coordination of the
      dihydroxy functionality of 1-(2'-carboxyethyl)-2-methyl-3-hydroxy-4-pyridinone to
      trivalent metal ions. By varying the amount of tannic acid, the hydrogel
      stiffness can be customized to a given application while retaining the self
      healing capabilities of the hydrogel's coordination chemical component.

PMID- 29202225
TI  - Synthesis, Characterization, and Biomedical Applications of a Targeted Dual-Modal
      Near-Infrared-II Fluorescence and Photoacoustic Imaging Nanoprobe.
AB  - Our development of multifunctional dual-modal imaging probes aims to integrate
      the benefits from both second near-infrared (NIR-II) fluorescence (1000-1700 nm)
      and photoacoustic imaging with an ultimate goal of improving overall cancer
      diagnosis efficacy. Herein we designed a donor-acceptor chromophore based
      nanoparticle (DAP) as a dual-modal image contrast agent has strong absorption in
      the NIR-I window and a strong fluorescence emission peak in the NIR-II region.
      The dual-modal DAPs composed of D-pi-A-pi-D-type chromophores were PEGylated
      through nanoprecipitation. The multifunctional DAP surface was thus available for
      subsequent bioconjugation of EGFR Affibody (Ac-Cys-ZEGFR:1907) to target EGFR
      positive cancers. The Affibody-conjugated DAPs appeared as highly monodisperse
      nanoparticles (~30 nm) with strong absorption in the NIR-I window (at ca. 680 nm)
      and an extremely high fluorescence in the NIR-II region (maximum peak at 1000
      nm). Consequently, the Affibody-DAPs show significantly enhanced photoacoustic
      and NIR-II fluorescence contrast effects in both in vitro and in vivo
      experiments. Moreover, the Affibody-DAPs have the capability to selectively
      target EGFR-positive tumors in an FTC-133 subcutaneous mouse model with
      relatively high photoacoustic and fluorescent signals. By taking advantage of
      high spatial resolution and excellent temporal resolution, photoacoustic/NIR-II
      fluorescence imaging with targeted dual-modal contrast agents allows us to
      specifically image and detect various cancers and diseases in an accurate manner.

PMID- 29202226
TI  - Stretchable Ti3C2Tx MXene/Carbon Nanotube Composite Based Strain Sensor with
      Ultrahigh Sensitivity and Tunable Sensing Range.
AB  - It remains challenging to fabricate strain-sensing materials and exquisite
      geometric constructions for integrating extraordinary sensitivity, low strain
      detectability, high stretchability, tunable sensing range, and thin device
      dimensions into a single type of strain sensor. A percolation network based on
      Ti3C2Tx MXene/carbon nanotube (CNT) composites was rationally designed and
      fabricated into versatile strain sensors. This weaving architecture with
      excellent electric properties combined the sensitive two-dimensional (2D) Ti3C2Tx
      MXene nanostacks with conductive and stretchable one-dimensional (1D) CNT
      crossing. The resulting strain sensor can be used to detect both tiny and large
      deformations with an ultralow detection limit of 0.1% strain, high stretchability
      (up to 130%), high sensitivity (gauge factor up to 772.6), tunable sensing range
      (30% to 130% strain), thin device dimensions (<2 MUm), and excellent reliability
      and stability (>5000 cycles). The versatile and scalable Ti3C2Tx MXene/CNT strain
      sensors provide a promising route to future wearable artificial intelligence with
      comprehensive tracking ability of real-time and in situ physiological signals for
      health and sporting applications.

PMID- 29202227
TI  - Control of Doping Level in Semiconductors via Self-Limited Grafting of Phosphorus
      End-Terminated Polymers.
AB  - An effective bottom-up technology for precisely controlling the amount of dopant
      atoms tethered on silicon substrates is presented. Polystyrene and poly(methyl
      methacrylate) polymers with narrow molecular weight distribution and end
      terminated with a P-containing moiety were synthesized with different molar mass.
      The polymers were spin coated and subsequently end-grafted onto nondeglazed
      silicon substrates. P atoms were bonded to the surface during the grafting
      reaction, and their surface density was set by the polymer molar mass, according
      to the self-limiting nature of the "grafting to" reaction. Polymeric material was
      removed by O2 plasma hashing without affecting the tethered P-containing moieties
      on the surface. Repeated cycles of polymer grafting followed by plasma hashing
      led to a cumulative increase, at constant steps, in the dose of P atoms grafted
      to the silicon surface. P injection in the silicon substrate was promoted and
      precisely controlled by high-temperature thermal treatments. Sheet resistance
      measurements demonstrated effective doping of silicon substrate.

PMID- 29202228
TI  - Acid-Assisted Exfoliation toward Metallic Sub-nanopore TaS2 Monolayer with High
      Volumetric Capacitance.
AB  - Conductive porous structures are favorable as active electrode materials for
      energy storage by boosting the active sites and specific surface area but have
      been rarely achieved in transition metal dichalcogenides. Here, we developed acid
      assisted exfoliation for the first time, to successfully exfoliate TaS2 into very
      large-sized conductive monolayers with controllable in-plane sub-nanopores. By
      inducing both interlayer lattice expansion and basal in-plane etching, hydrogen
      ion, previously regarded disastrous in charged system, was creatively utilized as
      an efficient and easily accessible assistant in simultaneous exfoliation and
      controllable structural modification. Benefiting from pore size (~0.95 nm)
      matching well with electrolyte ion size, coexistence of ultrahigh conductivity
      and fast ion transport was achieved in metallic large-sized monolayers. Notably,
      the as-produced TaS2-based electrode delivers large volumetric capacitance (508
      F/cm3 at scan rate of 10 mV/s) and high energy density (58.5 Wh/L) when
      fabricated into a micro-supercapacitor. We anticipate acid-assisted exfoliation
      to be a promising strategy in constructing 2D nanomaterials with novel structure
      for wide energy applications.

PMID- 29202229
TI  - 18F-Radiolabeling and In Vivo Analysis of SiFA-Derivatized Polymeric Core-Shell
      Nanoparticles.
AB  - Nanoparticles represent the most widely studied drug delivery systems targeting
      cancer. Polymeric nanoparticles can be easily generated through a microemulsion
      polymerization. Herein, the synthesis, radiolabeling, and in vivo evaluation of
      nanoparticles (NPs) functionalized by an organosilicon fluoride acceptor (SiFA)
      are reported which can be radiolabeled without further chemical modifications.
      Four nanoparticles in the sub-100 nm range with distinct hydrodynamic diameters
      of 20 nm (NP1), 33 nm (NP2), 45 nm (NP3), and 72 nm (NP4), respectively, were
      synthesized under size-controlled conditions. The SiFA-labeling building block
      acted as an initiator for the polymerization of polymer P1. The nanoparticles
      were radiolabeled with fluorine-18 (18F) through simple isotopic exchange (IE)
      and analyzed in vivo in a murine mammary tumor model (EMT6). The facile 18F
      radiolabeling SiFA methodology, performed in ethanol under mild reaction
      conditions, gave radiochemical yields (RCYs) of 19-26% and specific activities
      (SA) of 0.2-0.3 GBq/mg. Based on preclinical PET analysis, the tumor uptake and
      clearance profiles were analyzed depending on particle size. The nanoparticle
      size of 33 nm showed the highest tumor accumulation of SUVmean 0.97 (= 4.4%ID/g)
      after 4 h p.i. through passive diffusion based on the Enhanced Permeability and
      Retention (EPR) effect. Overall, this approach exhibits a simple, robust, and
      reliable synthesis of 18F radiolabeled polymeric nanoparticles with a favorable
      in vivo evaluation profile. This approach represents a straightforward
      synthetically accessible alternative to produce radiolabeled nanoparticles
      without any further surface modification to attach a radioisotope.

PMID- 29202230
TI  - The Forbidden 11Bu- Excited Singlet State in Peridinin and Peridinin Analogues.
AB  - Theoretical studies have predicted the presence of a forbidden 11Bu- state in
      proximity to the strongly allowed 11Bu+ excited state in polyenes and
      carotenoids. The 11Bu- state is invariably predicted to have a very low
      oscillator strength, which precludes direct optical spectroscopic assignment. We
      report here a direct UV-vis optical spectroscopic feature assigned to the 11Bu-
      state of S-2-peridinin, a synthetic analogue of the naturally occurring
      carotenoid, peridinin. The shift of the ground state dipole of S-2-peridinin
      compared to natural peridinin enhances the oscillator strength of absorption from
      the ground state to the 11Bu- state by 2 orders of magnitude relative to
      peridinin. It is postulated that this is due to a quadrupolar electrostatic field
      generated from the more central location of the lactone ring along the polyene
      chain in S-2-peridinin. MNDO-PSDCI and EOM-CCSD calculations provide a
      theoretical basis for this assignment and explain the unique properties of the
      11Bu- state and why the transition from the ground state to this state has such a
      low oscillator strength in most other polyenes and carotenoids.

PMID- 29202231
TI  - Identification of Novel Aurora Kinase A (AURKA) Inhibitors via Hierarchical
      Ligand-Based Virtual Screening.
AB  - Aurora kinases are essential for cell mitosis, amplified, and overexpressed in
      various human malignancies. Therefore, Aurora kinases have been promising targets
      for anticancer therapies, which has prompted an intensive search for their small
      molecule inhibitors. In this work, we performed a hierarchical and time-efficient
      virtual screening cascade for scaffold hopping, aiming to obtain structurally
      novel and highly potent hit compounds targeting Aurora kinases. The cascade
      consisted of a shape- and an electrostatic-based protocol, combined with a QSAR
      based selection protocol. This virtual screening cascade was used to screen two
      databases, one commercial database named the J&K database containing about 5.2
      million diverse molecules and the Drugbank database. Experimental validations led
      to the identification of one structurally novel and highly potent hit compound
      (hit 1, found to possess an IC50 of 8.1 and 19 nM for Aurora kinases A and B,
      respectively), which can be a promising starting point for further exploration.
      Additionally, Aurora kinases were identified as off-targets for hits 2-6
      (Crizotinib, CI-1033, Dasatinib, Bosutinib, MLN-518), which are approved or
      investigational drugs as listed in Drugbank, plausibly suggesting targeting
      Aurora kinases may even contribute to their mechanism of action.

PMID- 29202232
TI  - Nucleic Acid Biosensor Synthesis of an All-in-One Universal Blocking Linker
      Recombinase Polymerase Amplification with a Peptide Nucleic Acid-Based Lateral
      Flow Device for Ultrasensitive Detection of Food Pathogens.
AB  - In this study, a whole-course nucleic-acid-constructed biosensor that combines
      the all-in-one concepts of the universal blocking linker recombinase polymerase
      amplification (UBLRPA) and a peptide nucleic acid (PNA)-based lateral flow device
      (PLFD) has been developed for the ultrasensitive detection of food pathogens.
      Using the preamplification UBLRPA principle, a universal linker and C3 space
      blocker were utilized to produce the universal linker single-duplex DNA products.
      The developed amplification system was employed to convert duplex products to a
      single strand. In the signal recognition strategy, a special PNA probe was
      successfully employed in the portable PLFD. The UBLRPA products were identified
      visually using the PLFD through dual hybridization (a PNA probe on the gold
      nanoparticle (Au-NP) was combined with a universal linker on the end of the
      products; a PNA capture probe was used on the test line and a universal linker on
      the other end of the products). The accumulation of Au-NPs produced a
      characteristic red band, enabling the visual detection of a food pathogen without
      further testing. To demonstrate the value of the all-in-one biosensor, Salmonella
      enterica subsp. enterica serovar typhimurium was used as a model organism. The
      biosensor showed high selectivity and extraordinary repeatability using S.
      typhimurium, and the limit of detection was 4 CFU mL-1. Furthermore, when milk
      samples artificially contaminated with S. typhimurium were analyzed, the analysis
      was completed within 30 min without complicated instrumentation. The results
      exhibited good precision and recovery. This portable all-in-one biosensor
      demonstrates great promise for the screening of pathogens in food and
      environmental samples.

PMID- 29202233
TI  - Synthesis and Investigation of Photophysical and Biological Properties of Novel S
      Containing Bacteriopurpurinimides.
AB  - Novel hybrid molecule containing 2-mercaptoethylamine was synthesized starting
      from O-propyloxime-N-propoxy bacteriopurpurinimide (dipropoxy-BPI), which was
      readily oxidized in oxygen atmosphere yielding the corresponding disulfide
      analogue (disulfide-BPI). Spectral, photophysical, photodynamic, and biological
      properties of compound were properly evaluated. Compounds bearing disulfide
      moiety can directly interact with glutathione (GSH), thereby reducing its
      intracellular concentration. Indeed, mice sarcoma S37 cell line was treated in
      vitro with disulfide-BPI, yielding a CC50 value of 0.05 +/- 0.005 MUM. A
      relatively high level of singlet oxygen was detected. It was demonstrated (by
      fluorescence) that the PS was rapidly accumulated in a cancer nest (S37) at a
      relatively high level after 2 h upon intravenous administration. After 24 h, no
      traces of the molecule were detected in the tumor mass. Moreover, high
      photodynamic efficiency was demonstrated at doses of 150-300 J/cm2 against two
      different in vivo tumor models, achieving 100% regression of cancer growth.

PMID- 29202234
TI  - Halogen Bonding Interactions: Revised Benchmarks and a New Assessment of Exchange
      vs Dispersion.
AB  - We present a new analysis of exchange and dispersion effects for calculating
      halogen-bonding interactions in a wide variety of complex dimers (69 total)
      within the XB18 and XB51 benchmark sets. Contrary to previous work on these
      systems, we find that dispersion plays a more significant role than exact
      exchange in accurately calculating halogen-bonding interaction energies, which
      are further confirmed by extensive SAPT analyses. In particular, we find that
      even if the amount of exact exchange is nonempirically tuned to satisfy known DFT
      constraints, we still observe an overall improvement in predicting dissociation
      energies when dispersion corrections are applied, in stark contrast to previous
      studies ( Kozuch, S.; Martin, J. M. L. J. Chem. Theory Comput. 2013 , 9 , 1918 -
      1931 ). In addition to these new analyses, we correct several (14)
      inconsistencies in the XB51 set, which is widely used in the scientific
      literature for developing and benchmarking various DFT methods. Together, these
      new analyses and revised benchmarks emphasize the importance of dispersion and
      provide corrected reference values that are essential for
      developing/parametrizing new DFT functionals, specifically for complex halogen
      bonding interactions.

PMID- 29202235
TI  - Tuning Nanoparticle-Micelle Interactions and Resultant Phase Behavior.
AB  - The evolution of the interaction between an anionic nanoparticle and a nonionic
      surfactant and their resultant phase behavior in aqueous solution in the presence
      of electrolyte and ionic surfactants have been studied. The mixed system of
      anionic silica nanoparticles (Ludox LS30) with nonionic surfactant decaethylene
      glycol monododecylether (C12E10) forms a highly stable clear phase over a wide
      concentration range of surfactant. Small-angle neutron scattering (SANS) and
      dynamic light scattering data show that the surfactant micelles adsorb on the
      surface of the nanoparticle, resulting in micellar-decorated nanoparticle
      structures. With the addition of a small amount of electrolyte into this system,
      the stability gets disturbed substantially and turns to a two-phase (turbid)
      system. The evolution of interaction in this system has been examined, and it was
      found that micelle-induced long-range depletion attraction (modeled by a double
      Yukawa potential) between nanoparticles leads to their aggregation.
      Interestingly, the addition of anionic surfactant sodium dodecyl sulfate (SDS) in
      this two-phase system transforms it to a transparent one-phase state, suppressing
      the depletion-mediated aggregation of nanoparticles. This is attributed to the
      formation of anionic C12E10-SDS mixed micelles, and it is their repulsive micelle
      micelle interaction that disrupts the depletion phenomenon. On the other hand,
      the addition of cationic surfactant dodecyl trimethylammonium bromide (DTAB) to
      the turbid LS30-C12E10 electrolyte system shows no change in the turbidity
      arising from an aggregated nanoparticle system. The driving interaction, in this
      case, is different from that of the surfactant-mediated depletion attraction; it
      is due to the attraction between the nanoparticles mediated by the presence of
      oppositely charged DTAB micelles between them, resulting in a charge-driven
      bridging aggregation of nanoparticles. Each of these multicomponent systems has
      been investigated using contrast variation SANS measurements for different
      contrast conditions where the role of individual components (nanoparticle or
      surfactant) in the mixed system has been selectively studied. These results thus
      show that nanoparticle-surfactant micelle interactions can be tuned by the
      presence of electrolyte and/or choice of surfactant combination.

PMID- 29202237
TI  - Impact of Solid-State Form on the Disproportionation of Miconazole Mesylate.
AB  - Approximately 50% of solid oral dosage forms utilize salt forms of the active
      pharmaceutical ingredient (API). A major challenge with the salt form is its
      tendency to disproportionate to produce the un-ionized API form, decreasing the
      solubility and negatively impacting product stability. However, many of the
      factors dictating the tendency of a given salt to undergo disproportionation
      remain to be elucidated. In particular, the role of the solid-state properties of
      the salt on the disproportionation reaction is unknown. Herein, various solid
      forms of a model salt, miconazole mesylate (MM), were evaluated for their
      tendency to undergo disproportionation when mixed with basic excipients, namely
      tribasic sodium phosphate dodecahydrate (TSPd) and croscarmellose sodium (CCS),
      and exposed to moderate relative humidity storage conditions. It was observed
      that the rate and extent of salt disproportionation were significantly different
      for the various solid forms of MM. As expected, the amorphous salt was highly
      susceptible to disproportionation, while the dihydrate salt form was resistant to
      conversion under the conditions tested. In addition, binary excipient blends of
      amorphous and anhydrous forms exhibited a reduced extent of disproportionation at
      a higher relative humidity storage condition. This was due to the competitive
      kinetics between disproportionation to the free base and conversion to the
      dihydrate salt form. The results of this study provide important insights into
      the impact of solid-state form on susceptibility to disproportionation that can
      be utilized for rationally designing robust pharmaceutical formulations.

PMID- 29202236
TI  - Vibrational Changes Induced by Electron Transfer in Surface Bound Azurin
      Metalloprotein Studied by Tip-Enhanced Raman Spectroscopy and Scanning Tunneling
      Microscopy.
AB  - The copper protein azurin, due to the peculiar coupling of its optical and
      vibronic properties with electron transfer (ET) and its biorecognition
      capabilities, is a very promising candidate for bioelectronic, bio-optoelectronic
      and biosensor applications. However, a complete understanding of the fundamental
      processes relating azurin ET and its optical and vibronic characteristics with
      the charge transport mechanisms occurring in proteins bound to a conductive
      surface, the typical scenario for a biosensor or bioelectronic component, is
      still lacking. We studied azurin proteins bound to a gold electrode surface by
      scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy (STM
      TERS). Robust TER spectra were obtained, and the protein's vibronic response
      under optical excitation in resonance with its ligand-to-metal charge transfer
      band was found to be affected by the tunneling parameters, indicating a direct
      involvement of the active site vibrations in the electron transport process.

PMID- 29202239
TI  - Capillary-Enhanced Immobilization of Nanoparticles.
AB  - The contact between a spherical nanoparticle and a planar substrate is surrounded
      by an annular wedge cavity. In adsorption processes, this acts like a small pore.
      Interfacial/capillarity effects lead to an accumulation of adsorbate in this
      region ("capillary condensation"). This effectively increases the contact area
      between the particles and the substrate. Thus, capillary-enhanced adsorbate
      accumulation increases the adhesion between the nanoparticles and the planar
      surface, which effectively immobilizes the particles.

PMID- 29202238
TI  - Finite-Size and Solvent Dependent Line Tension Effects for Nanoparticles at the
      Air-Liquid Surface.
AB  - The line tension for a nanoparticle (NP) at the air-liquid surface can be
      determined by examining the variation in NP solution surface tension with bulk NP
      concentration. In this publication the variation in line tension with liquid
      solvent is examined for the homologous series of liquids from n-decane through to
      n-octadecane. Finite-size line tension effects are also studied by examining the
      variation in line tension with NP size for NPs at the air-octadecane surface.
      Both the line tension variation with solvent and NP size can be qualitatively
      explained using an interface displacement model for the line tension.

PMID- 29202240
TI  - Anchoring Energy Measurements at the Aqueous Phase/Liquid Crystal Interface with
      Cationic Surfactants Using Magnetic Freedericksz Transition.
AB  - We constructed the apparatus to observe the Freedericksz transition of liquid
      crystal in contact with water. The Freedericksz transition is a distortion of
      nematic liquid crystals (LCs) induced by external fields. In the present system,
      sweeping homogeneous magnetic field was applied to the sample, and the distortion
      of the LC was visualized with a polarized light microscope with the crossed
      Nichols configuration. The anchoring energy (WAQ/LC) at the aqueous phase/LC
      interface was measured in the presence of surfactant from the threshold magnetic
      field of the Freedericksz transition. We studied two cationic surfactants:
      dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide. A
      nematic LC, 4-cyano-4'-pentylbiphenyl (5CB), was examined, which was confined in
      a copper grid on an octadecyltrichlorosilane-treated microscope glass plate.
      Measured WAQ/LC were reproducible and showed consistence with the reported region
      for the water/LC interface. Interfacial excess of surfactants was also measured
      by the pendant drop method, and the relationship between the obtained WAQ/LC and
      the interfacial excess was investigated. Experiments showed that an increase in
      the anchoring energy depends on the surfactant and its interfacial excess. The
      region of the interfacial coverage, at which WAQ/LC increases, varied with the
      chain length of the surfactant. The measurement of the anchoring energy will
      provide new fundamental information on aqueous phase/LC interface.

PMID- 29202241
TI  - Ranking the Stability of Transition-Metal Complexes by On-Surface Atom Exchange.
AB  - Surface-adsorbed macrocycles exhibit a number of interesting physical and
      chemical properties; many of them are determined by their transition-metal
      centers. The hierarchical exchange of the central metal atom in such surface
      adsorbed complexes is demonstrated, specifically in the porphyrin-like macrocycle
      pyrphyrin adsorbed on Cu(111). Using scanning tunneling microscopy and X-ray
      photoelectron spectroscopy, we show that Cu as central metal atom is easily
      exchanged with Ni or Fe atoms supplied in trace amounts to the surface. Atom
      exchange of Ni centers with Fe atoms also occurs, with moderate yield. These
      results allow ranking the stability of the surface-adsorbed Cu, Ni, and Fe
      complexes. The fact that the atom exchange occurs at 423 K shows that surface
      adsorbed macrocycles can be surprisingly easily transformed.

PMID- 29202242
TI  - Molybdenum Oxide Cluster Anion Reactions with C2H4 and H2O: Cooperativity and
      Chemifragmentation.
AB  - To probe the mechanism of sacrificial reagents in catalytic processes, product
      distributions from MoxOy- clusters reacting individually with C2H4 and H2O are
      compared with those from reactions with a C2H4 + H2O mixture, with the
      thermodynamics explored computationally. These molecules were chosen to model
      production of H2 from H2O via H2O + C2H4 -> H2 + CH3CHO, mediated by MoxOy-
      clusters. H2O is known to sequentially oxidize MoxOy- suboxide clusters while
      producing H2, resulting in less reactive clusters. MoxOy- (y ~ x) clusters
      undergo chemi-fragmentation reactions with C2H4, with MoxOyC2Hz- complexes
      forming as the cluster oxidation state increases. Unique species observed in
      reactions with the C2H4 + H2O mixture, Mo2O5C2H2- and MoO3C2H4-, suggest that the
      internal energy gained in new Mo-O bond formation from oxidation by H2O opens
      additional reaction channels. C2H3O- is observed uniquely in reactions with the
      C2H4 + H2O mixture, giving indirect evidence of CH3CHO formation via the cluster
      mediated H2O + C2H4 -> H2 + CH3CHO reaction; C2H3O- can form via dissociative
      electron attachment to CH3CHO. Calculations support mechanisms that invoke
      participation of two ethylene molecules on thermodynamically favorable pathways
      leading to experimentally observed products.

PMID- 29202243
TI  - Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross
      Coupling.
AB  - An asymmetric Ni-catalyzed reductive cross-coupling has been developed to prepare
      enantioenriched allylic silanes. This enantioselective reductive alkenylation
      proceeds under mild conditions and exhibits good functional group tolerance. The
      chiral allylic silanes prepared here undergo a variety of stereospecific
      transformations, including intramolecular Hosomi-Sakurai reactions, to set
      vicinal stereogenic centers with excellent transfer of chirality.

PMID- 29202244
TI  - Shear-Induced Alignment of Anisotropic Nanoparticles in a Single-Droplet
      Oscillatory Microfluidic Platform.
AB  - Flow-induced alignment of shape-anisotropic colloidal particles is of great
      importance in fundamental research and in the fabrication of structurally
      anisotropic materials; however, rheo-optical studies of shear-induced particle
      orientation are time- and labor-intensive and require complicated experimental
      setups. We report a single-droplet oscillatory microfluidic strategy integrated
      with in-line polarized light imaging as a strategy for studies of shear-induced
      alignment of rod-shape nanoparticles. Using an oscillating droplet of an aqueous
      isotropic suspension of cellulose nanocrystals (CNCs), we explore the effect of
      the shear rate and suspension viscosity on the flow-induced CNC alignment and
      subsequent relaxation to the isotropic state. The proposed microfluidic strategy
      enables high-throughput studies of shear-induced orientations in structured
      liquid under precisely controlled experimental conditions. The results of such
      studies can be used in the development of structure-anisotropic materials.

PMID- 29202245
TI  - Chemical and Physical Variability in Structural Isomers of an l/d alpha-Sheet
      Peptide Designed To Inhibit Amyloidogenesis.
AB  - There has been much interest in synthetic peptides as inhibitors of aggregation
      associated with amyloid diseases. Of particular interest are compounds that
      target the cytotoxic soluble oligomers preceding the formation of mature,
      nontoxic fibrils. This study explores physical and chemical differences between
      two de novo-designed peptides that share an identical primary structure but
      differ in backbone chirality at six key positions. We show that the presence of
      alternating l/d-amino acid motifs dramatically increases aqueous solubility,
      enforces alpha-sheet secondary structure, and inhibits aggregation of the beta
      amyloid peptide implicated in Alzheimer's disease, in addition to neutralizing
      its cytotoxicity. In contrast, the all-l-amino acid isomer does not form alpha
      sheet structure and is insoluble and inactive.

PMID- 29202247
TI  - Multicolor Spectral-Specific Silicon Nanodetectors based on Molecularly Embedded
      Nanowires.
AB  - Silicon-based photodetectors cannot distinguish between different wavelengths.
      Therefore, these detectors relay on color-specific filters to achieve color
      separation. Color filters add complexity to color sensitive device fabrication,
      and hinder miniaturization of such devices. Here, we report an ultrasmall (as
      small as ~20 nm by 300 nm), red-green-blue-violet (RGBV) filter-free spectrally
      gated field effect transistor (SGFET) detectors. These photodetectors are based
      on organic-silicon nanowire hybrid FET devices, capable of detecting specific
      visible wavelength spectrum with full width at half-maxima (fwhm) under 100 nm.
      Each SGFET is controlled by a distinctive RGBV spectral range, according to its
      specific organic fluorophore functionalization. The spectral-specific RGBV
      detection is accomplished via covalent attachment of different fluorophores. The
      fluorophore molecules inject electrons into the nanowire structure as a result of
      light absorption at the appropriate RGBV spectral range. These photoinduced
      electrons modify the occupancies of the oxide's surface states, shifting the
      device threshold voltage, thus changing its conductivity, and functioning as a
      negative stress bias in a p-type SiNW FETs. A positive biasing can be achieved
      via UV light-induced ionization, which leads to detrapping and translocation of
      electrons at the oxide layer. Furthermore, a novel theoretical model on the
      mechanism of action of these devices was developed. Also, we show that suspended
      SGFETs can function as nonvolatile memory elements, which unlike fast-relaxing on
      surface SGFETs, can store discrete "on" (RGBV illumination) and "off" (UV
      illumination) states for several days at ambient conditions. We also demonstrate
      a unique single-nanowire multicolor photodetector, enabling in principle a broad
      spectral detection over a single silicon nanowire element. These highly compact,
      spectral-controlled nanodevices have the potential to serve in various future
      novel optoelectric applications.

PMID- 29202246
TI  - O-GalNAcylation of RANTES Improves Its Properties as a Human Immunodeficiency
      Virus Type 1 Entry Inhibitor.
AB  - Many human proteins have the potential to be developed as therapeutic agents.
      However, side effects caused by direct administration of natural proteins have
      significantly slowed expansion of protein therapeutics into the clinic. Post
      translational modifications (PTMs) can improve protein properties, but because of
      significant knowledge gaps, we are considerably limited in our ability to apply
      PTMs to generate better protein therapeutics. Here, we seek to fill the gaps by
      studying the PTMs of a small representative chemotactic cytokine, RANTES. RANTES
      can inhibit HIV-1 infection by competing with it for binding to receptor CCR5 and
      stimulating CCR5 endocytosis. Unfortunately, RANTES can induce strong signaling,
      leading to severe inflammatory side effects. We apply a chemical biology approach
      to explore the potential of post-translationally modified RANTES as safe
      inhibitors of HIV-1 infection. We synthesized and systematically tested a library
      of RANTES isoforms for their ability to inhibit inflammatory signaling and
      prevent HIV-1 infection of primary human cells. Through this research, we
      revealed that most of the glycosylated variants have decreased inflammation
      associated properties and identified one particular glyco variant, a truncated
      RANTES containing a Galbeta1-3GalNAc disaccharide alpha-linked to Ser4, which
      stands out as having the best overall properties: relatively high HIV-1
      inhibition potency but also weak inflammatory properties. Moreover, our results
      provided a structural basis for the observed changes in the properties of RANTES.
      Taken together, this work highlights the potential importance of glycosylation as
      an alternative strategy for developing CCR5 inhibitors to treat HIV-1 infection
      and, more generally, for reducing or eliminating unwanted properties of
      therapeutic proteins.

PMID- 29202248
TI  - Bag Valve Mask Ventilation as a Perceptual-Cognitive Skill.
AB  - Objective This study used a high-fidelity infant mannequin to examine the
      relationship between the quality of bag valve mask ventilation (BVMV) and how
      providers of varying levels of experience use visual feedback (e.g., electronic
      vital signs) to guide their performance. Background BVMV is a common and critical
      procedure for managing pediatric respiratory emergencies. However, providers do
      not consistently deliver effective BVMV. Efforts to improve BVMV have ignored the
      question of how providers effectively use feedback often available during BVMV.
      Method Six expert and six novice respiratory therapists completed two simulations
      of an infant requiring BVMV. In one, the technology failed to display SpO2, an
      important but somewhat redundant visual cue. Eye movements, verbal reports, and
      ventilation rate (in breaths per minute) were measured in each simulation.
      Results Regardless of SpO2 availability, eye movements and verbal reports
      suggested that novices depended strongly on electronic vital signs and when SpO2
      was absent ventilated at a faster rate (exceeding the recommended range of
      ventilation rates) than when SpO2 was present. Experts' ventilation rates were
      comparable and within the recommended range in both conditions. When SpO2 was
      absent, experts emphasized information from direct observation of the patient
      that novices neglected. Conclusion Individual differences in the use of feedback
      during BVMV contribute to the quality of BVMV. This work bears on the theoretical
      discussions involving the use of automation and nontechnological cues to guide
      performance. Application These results have the potential to expand the current
      understanding of factors underlying effective BVMV with implications for training
      novice providers.

PMID- 29202249
TI  - Smoke-Free Home and Vehicle Policies Among Community College Smokers.
AB  - BACKGROUND: Personal smoke-free policies (home and vehicle) reduce secondhand
      smoke exposure, improve health, and increase quitting among smokers. Overall,
      83.0% and 78.1% of Americans report smoke-free homes and vehicles, respectively.
      However, little is known about such policies among 2-year community college (CC)
      students, who represent a large, diverse population with higher smoking rates and
      less negative attitudes toward smoking than 4-year college students. METHODS:
      Prevalence of, and factors associated with, personal smoke-free policies were
      examined for 2,475 CC smokers enrolled in a national trial of web-assisted
      tobacco intervention. RESULTS: Few students had smoke-free home policies (20.7%),
      smoke-free vehicles (17.0%), both smoke-free home and vehicle policy (4.2%), or
      any policy (home or vehicle; 31.2%). In logistic regression models, having
      children was associated with a smoke-free home or any policy but not with a smoke
      free vehicle, and among participants who had children, only 20% reported a smoke
      free home, and only 15% had a smoke-free vehicle. In addition, not living with
      other smokers, living with parents or roommates/siblings (vs. alone), smoking
      later than 30 minutes after awakening, believing that smoking affects the health
      of others, and confidence in quitting were associated with presence of a smoke
      free home or any policy; no variables were significantly associated with presence
      of a smoke-free vehicle. CONCLUSIONS: CC students represent a priority population
      for intervention regarding smoke-free homes and vehicles. Such intervention can
      decrease exposure of others, including children, and potentially increase the
      likelihood of quitting in this high-risk population.

PMID- 29202250
TI  - Systemic granulomatous disease in dairy cattle during a dicyandiamide feeding
      trial.
AB  - CASE HISTORY: Mature, in-calf, non-lactating, Friesian or Friesian-cross cows
      were fed dicyandiamide (DCD) at daily doses of 0.15 g/kg (Group 1; n=31), 0.45
      g/kg (Group 2; n=21) and 0.75 g/kg (Group 3; n=12), as part of a safety trial,
      which also included a control group (n=15). Daily health observations were
      carried out on each cow until Day 86 of the study. On Day 28 one cow from Group 3
      was observed with signs of disease, and subsequently disease was noted in other
      cows. CLINICAL FINDINGS: Clinical signs in the first case included depression,
      pyrexia (40.9 degrees C), salivation and dehydration, in addition to progressive
      weight loss, followed by death on Day 32. Other cows from all treatment groups
      developed clinical signs of disease resulting in euthanasia of seven animals.
      Disease occurred in 10/12 (83%) cows in Group 3, 11/21 (52%) cows in Group 2, and
      7/31 (23%) cows in Group 1. Clinical signs were variable and included dermatitis
      and pruritus of the head and neck, petechial haemorrhages, pyrexia, weight loss,
      thrombocytopenia, neutropenia, and regenerative anaemia. PATHOLOGICAL FINDINGS:
      Gross findings included generalised lymphadenopathy, subcutaneous oedema,
      petechiation of mucosal and serosal surfaces, and gastrointestinal haemorrhage.
      Histologically, multiple organs and tissues contained inflammatory foci
      characterised by infiltrates of lymphocytes, plasma cells, macrophages and
      occasionally prominent multinucleated giant cells and eosinophils. DIAGNOSIS:
      Multisystemic granulomatous and haemorrhagic syndrome resembling cell-mediated
      hypersensitivity, associated with DCD ingestion. CLINICAL RELEVANCE: This is the
      first report of toxicity in cattle associated with ingestion of DCD. The
      proportion of affected cows increased with increasing dose of DCD, but not all
      cattle in the high dose group developed disease, therefore additional factors may
      determine whether or not an individual cow will develop DCD-associated disease.

PMID- 29202251
TI  - Determining the optimum capacity to train: a challenge for the College of
      Intensive Care Medicine of Australia and New Zealand.

PMID- 29202252
TI  - The case for more pilot studies.

PMID- 29202253
TI  - The evolution of intensive care medicine: a personal journey.

PMID- 29202254
TI  - Incidence, correlates and outcomes associated with falls in the intensive care
      unit: a retrospective cohort study.
AB  - BACKGROUND: Falls among hospitalised patients contribute to avoidable morbidity
      and prolonged hospital stay. We aimed to describe the incidence, circumstances
      and outcomes associated with patient falls occurring in intensive care units.
      METHODS: Retrospective cohort study of adult admissions to an academic, tertiary
      ICU in Edmonton, Canada between 1 January 2013 and 30 April 2016. Fall events
      were ascertained by interrogation of an electronic health record. Each fall was
      independently adjudicated by two intensivists to confirm that a fall did occur,
      and to determine if the fall was potentially avoidable. Agreement was assessed by
      intraclass correlation (ICC). A matched cohort (one fall to five non-fall) was
      created to compare course and outcomes. RESULTS: Of 31 events identified, 26 were
      adjudicated as a fall (84%), for an estimated incidence of 5.2 per 1000 ICU
      admissions (95% CI, 3.4-7.6). Of these, 23 were judged as avoidable (89%) (ICC,
      0.69; 95% CI, 0.37-0.85). The mean age was 54.5 years (SD, 17.4 years), 20 of the
      falls (77%) involved men, and 10 (39%) were surgical admissions (eight [31%] for
      trauma). The median ICU stay before the falls was 10.6 days (interquartile range
      [IQR], 6.2-15.0 days), and 13 patients (50%) scored positive for delirium. At the
      time of the fall, three patients (12%) were invasively ventilated, and eight
      (31%) were classified as ward-ready. Eleven falls (42%) were witnessed and 12
      (46%) occurred after hours, of which nine involved patients (75%) who had
      delirium. Seven falls (27%) occurred within 2 hours of a nursing shift change and
      11 (42%) during a nursing break coverage. No patient sustained a major injury
      related to a fall but four (15%) reported minor injuries such as a laceration or
      abrasion. The median ICU stay after a fall was 2.2 days (IQR, 1.2-2.9 days).
      Compared with the matched non-fall cohort, patients who fell had a longer
      duration of ICU stay (median, 12.0 days [IQR, 8.3-18.6 days] v 4.7 days [IQR, 2.8
      8.4 days]; P < 0.0001). CONCLUSION: Falls in the ICU are infrequent and generally
      perceived as avoidable. Falls often occur at night, are unwitnessed and are
      associated with concomitant patient delirium and nursing shift changes and cross
      coverage.

PMID- 29202255
TI  - Patterns of organ donation in children in Australia and New Zealand.
AB  - OBJECTIVES: Paediatric organ donation (OD) represents a small proportion of total
      OD in Australia and New Zealand. Our aim was to describe the patterns of
      paediatric OD, specifically, the demographic characteristics and donation
      outcomes over two time periods. DESIGN: We performed a retrospective study using
      national OD and intensive care registry data from intensive care units in
      Australia and New Zealand from 1 January 2000 to 31 December 2015. Data were
      analysed between two time periods. Paediatric data were compared with adult data.
      PARTICIPANTS: Organ donors aged under 16 years in paediatric and mixed adult and
      paediatric ICUs. RESULTS: There were 267 paediatric organ donors, representing
      5.4% of all donors. The rate of OD as a percentage of ICU deaths was comparable
      to adults (6.0% v 4.6%; P < 0.001). Over the entire period, donations after brain
      death totalled 244 (91.4%), and donations after circulatory death (DCDs) totalled
      23 (8.6%). DCDs increased from 0.7% to 17% between the time periods (P < 0.001).
      Children aged under 2 years had a lower rate of donation than the general
      paediatric cohort (1.2% v 6.0%; P < 0.001). CONCLUSIONS: Paediatric OD rates have
      not changed over time but are comparable to adults when expressed as a percentage
      of ICU deaths. Paediatric DCD has increased significantly over time.

PMID- 29202256
TI  - Long-term mortality of critically ill patients with diabetes who survive
      admission to the intensive care unit.
AB  - OBJECTIVE: Long-term outcomes of critically ill patients with diabetes are
      unknown. Our objectives were to evaluate the effect of diabetes on both long-term
      survival rates and the average number of years of life lost for patients admitted
      to an intensive care unit who survived to hospital discharge. DESIGN AND
      PARTICIPANTS: A data linkage study evaluating all adult patients in South
      Australia between 2004 and 2011 who survived hospitalisation that required
      admission to a public hospital ICU. MAIN OUTCOME MEASURES: All patients were
      evaluated using hospital coding for diabetes, which was crossreferenced with
      registration with the Australian National Diabetes Services Scheme for a
      diagnosis of diabetes. This dataset was then linked to the Australian National
      Death Index. Longitudinal survival was assessed using Cox proportional hazards
      regression. Life-years lost were calculated using age- and sex-specific life
      tables from the Australian Bureau of Statistics. RESULTS: 5450 patients with
      diabetes and 17 023 patients without diabetes were included. Crude mortality
      rates were 105.5 per 1000 person-years (95% CI, 101.6-109.6 per 1000 person
      years) for patients with diabetes, and 67.6 per 1000 person-years (95% CI, 65.9
      69.3 per 1000 personyears) for patients without diabetes. Patients with diabetes
      were older and had higher illness severity scores on admission to the ICU, were
      more likely to die after hospital discharge (unadjusted hazard ratio [HR], 1.52
      [95% CI, 1.45-1.59]; adjusted HR, 1.16 [95% CI, 1.10-1.21]; P < 0.0001) and
      suffered a greater number of average lifeyears lost. CONCLUSIONS: Our study
      indicates that crude mortality for ICU survivors with pre-existing diabetes is
      considerable after hospital discharge, and the risk of mortality is greater than
      for survivors without diabetes.

PMID- 29202257
TI  - Maintenance fluid practices in paediatric intensive care units in Australia and
      New Zealand.
AB  - BACKGROUND: Maintenance fluid administration is a common practice in paediatric
      intensive care units (PICUs), contributing to daily fluid intake and fluid
      balance, but little is known about this practice. OBJECTIVES: To determine the
      volume and type of maintenance fluid delivered to PICU patients, and to assess
      changes in practice compared with a previous time point. METHODS: A prospective,
      observational, single-day, point prevalence study of paediatric patients from 11
      Australian and New Zealand PICUs, conducted in 2014. RESULTS: Seventy-two
      patients were enrolled. The median age and weight of infants aged < 1 year (n =
      34) were 2 months (interquartile range [IQR],1-4) and 5 kg (IQR, 4-6),
      respectively; while in children >= 1 year of age (n = 38), these were 4 years
      (IQR, 2-8) and 17 kg (IQR, 12-23), respectively. On the study day, 19 infants
      (56%) and 19 children aged >= 1 year (50%) received maintenance fluids. Infants
      received a median of 23 mL/kg (IQR, 12-45) of maintenance fluid in addition to 51
      mL/kg (IQR, 40-72) of fluid and nutrition from other sources; maintenance fluids
      contributed 29% (IQR, 13%-60%) of the total daily fluid intake. Children >= 1
      year of age received a median of 18 mL/kg (IQR, 9-37) of maintenance fluid in
      addition to 39 mL/kg (IQR, 25-53) of fluid and nutrition from other sources;
      maintenance fluids contributed 33% (IQR, 17%-69%) of the total daily fluid
      intake. When compared with similar data from 2011, there was no change in the
      amount of maintenance fluid given, which was administered mostly as isotonic
      fluids. CONCLUSION: Maintenance fluid contributes about a third of total fluid
      administration in children in Australian and New Zealand PICUs and is mostly
      administered as isotonic solutions.

PMID- 29202258
TI  - The SPICE III study protocol and analysis plan: a randomised trial of early
      goaldirected sedation compared with standard care in mechanically ventilated
      patients.
AB  - BACKGROUND: Sedation strategy in critically ill patients who are mechanically
      ventilated is influenced by patient-related factors, choice of sedative agent and
      the intensity or depth of sedation prescribed. The impact of sedation strategy on
      outcome, in particular when delivered early after initiation of mechanical
      ventilation, is uncertain. OBJECTIVES: To present the protocol and analysis plan
      of a large randomised clinical trial investigating the effect of a sedation
      strategy, in critically ill patients who are mechanically ventilated, based on a
      protocol targeting light sedation using dexmedetomidine as the primary sedative,
      termed "early goal-directed sedation", compared with usual practice. METHODS:
      This is a multinational randomised clinical trial in adult intensive care
      patients expected to require mechanical ventilation for longer than 24 hours. The
      main exclusion criteria include suspected or proven primary brain pathology or
      having already been intubated or sedated in an intensive care unit for longer
      than 12 hours. Randomisation occurs via a secured website with baseline
      stratification by site and suspected or proven sepsis. The primary outcome is 90
      day all-cause mortality. Secondary outcomes include death, institutional
      dependency, cognitive function and health-related quality of life 180 days after
      randomisation, as well as deliriumfree, coma-free and ventilation-free days at 28
      days after randomisation. A predefined subgroup analysis will also be conducted.
      Analyses will be on an intention-to-treat basis and in accordance with this pre
      specified analysis plan. CONCLUSION: SPICE III is an ongoing large scale clinical
      trial. Once completed, it will inform sedation practice in critically ill
      patients who are ventilated.

PMID- 29202259
TI  - Bedside lung ultrasound in the care of the critically ill.
AB  - OBJECTIVE: To describe the technique and review the utility of bedside lung
      ultrasound in acute care. SUMMARY: Lung ultrasound is a useful point-of-care
      investigation in acute care, especially in patients with dyspnoea or haemodynamic
      instability. Although normal lung parenchyma is not accessible to ultrasound,
      distinctive artefacts arising from parietal and visceral pleura indirectly imply
      the presence of normal lung. As aeration of lung tissue reduces with disease
      process, visual assessment of several pathologic entities by ultrasound becomes
      possible. Ultrasound can be used for qualitative and quantitative assessment as
      well as to guide intervention. Compared with supine anteroposterior chest x-rays,
      lung ultrasound is faster and superior at ruling out pneumothorax and diagnosing
      lung consolidation, pleural effusions or pulmonary oedema. It is a logical and
      highly valuable extension of echocardiography and can be incorporated into
      diagnostic algorithms for assessment of dyspnoea, hypotension, chest pain or
      trauma. It provides rapid information about potentially reversible pathology in
      cardiac arrest scenarios. Other advantages include bedside availability,
      repeatability, provision of dynamic diagnostic information, ease of use and the
      absence of radiation exposure.

PMID- 29202260
TI  - Interobserver agreement for post mortem renal histopathology and diagnosis of
      acute tubular necrosis in critically ill patients.
AB  - BACKGROUND: The renal histopathology of critically ill patients dying with acute
      kidney injury (AKI) in intensive care units of high income countries remains
      uncertain. METHODS: Retrospective observational assessment of interobserver
      agreement in the reporting of renal post mortem histopathology, and the ability
      of pathologists blinded to the clinical context to independently identify the
      presence of pre-mortem AKI from digital images of histological sections from 34
      critically ill patients dying in teaching hospitals in Australia and Canada.
      RESULTS: We identified a heterogeneous cohort with a median age of 65 years
      (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and
      sepsis as the most common admission diagnosis (12/34; 35%). The most common
      proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34;
      21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and
      21 patients (62%) receiving renal replacement therapy. Structured reporting for
      tubular inflammation showed excellent agreement (kappa = 1), but no other
      subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair
      agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of
      moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I
      or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%;
      pathologist B predicted AKI with an accuracy of 35.3%. CONCLUSIONS: Post mortem
      assessment of the renal histopathology in critically ill patients is neither
      robust nor reproducible; independent pathologists agree poorly on the diagnosis
      of ATN, and their structural assessment appears dissociated from ante-mortem
      renal function.

PMID- 29202262
TI  - Pharmacodynamics of intravenous frusemide bolus in critically ill patients.

PMID- 29202261
TI  - Intensive care unit randomised trial comparing two approaches to oxygen therapy
      (ICU-ROX): results of the pilot phase.
AB  - OBJECTIVE: The objective of the intensive care unit randomised trial comparing
      two approaches to oxygen therapy (ICU-ROX) pilot phase, which included the first
      100 patients of an overall sample of 1000, was to examine feasibility. DESIGN:
      Investigator-initiated, prospective, parallel-group, pilot randomised controlled
      trial. SETTING: Six medical-surgical intensive care units (ICUs) in Australia and
      New Zealand, with participants recruited from September 2015 through June 2016.
      PARTICIPANTS: 100 patients >= 18 years of age who required invasive mechanical
      ventilation in the ICU and were expected to be receiving it beyond the next
      calendar day at the time of randomisation. INTERVENTIONS: Conservative oxygen
      therapy or standard care. MAIN OUTCOME MEASURES: Eligibility, recruitment rate,
      and separation in oxygen exposure (fraction of inspired oxygen [FiO2] and oxygen
      saturation measured by pulse oximetry [SpO2Z]). RESULTS: 94 of 99 participants
      (94.9%) were confirmed by study monitors to fulfil the study eligibility
      criteria. 3.6 patients per site per month were enrolled (95% confidence interval
      [CI], 2.5-4.7). Patients allocated to conservative oxygen therapy spent
      significantly more time on an FiO2 of 0.21 in the ICU; median, 31.5 hours
      (interquartile range [IQR], 7-63.5) for conservative oxygen therapy patients v 0
      hours for standard oxygen therapy patients (IQR, 0-10; midpoint difference, 21.5
      hours; 95% CI, 9-34; P < 0.0001). Patients allocated to conservative oxygen
      therapy spent less time in the ICU with an SpO2Z of >= 97% than patients
      allocated to standard oxygen therapy; median, 18.5 hours (IQR, 5-46) for
      conservative oxygen therapy patients v 32 hours for standard oxygen therapy (IQR,
      17-80; midpoint difference, 13.5 hours; 95% CI, 2-25; P = 0.02). CONCLUSIONS: Our
      findings confirm the feasibility of completing the ICU-ROX trial without the need
      for substantive changes to the study protocol for the remaining 900 trial
      participants. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
      Registry (ANZCTRN 12615000957594).

PMID- 29202263
TI  - Does Graft Particle Type and Size Affect Ridge Dimensional Changes After Alveolar
      Ridge Split Procedure?
AB  - PURPOSE: The absence of an adequate volume of bone at implant sites requires
      augmentation procedures before the placement of implants. The aim of the present
      study was to assess the ridge width gain with the use of allografts and biphasic
      beta-tricalcium phosphate with hydroxyapatite (alloplast) in ridge split
      procedures, when each were used in small (0.25 to 1 mm) and large (1 to 2 mm)
      particle sizes. PATIENTS AND METHODS: A randomized controlled trial of 23
      subjects with severe atrophy of the mandible in the horizontal dimension was
      conducted in a private institute. The patients underwent placement of 49 dental
      implants after a staged ridge split procedure. The patients were randomly
      allocated to alloplast and allograft groups (predictor variable). In each group,
      the patients were randomly assigned to either small graft particle or large graft
      particle size (predictor variable). The gain in ridge width (outcome variable)
      was assessed before implant placement. A 2-way analysis of variance test and the
      Student unpaired t test were used for evaluation of the ridge width gain between
      the allograft and alloplast groups (predictor variable). Differences were
      considered significant if P values were < .05. RESULTS: The sample included 23
      patients (14 men and 9 women). The patients were randomly allocated to the
      alloplast (n = 11) or allograft (n = 12) group before the ridge split procedure.
      In each group, they were assigned to a small graft particle or large graft
      particle size (alloplast group, small particle in 5 and large particle size in 6
      patients; allograft group, small particle in 6 and large particle size in 6). A
      statistically significant difference was observed between the 2 graft types. The
      average ridge width gain was significantly greater in the alloplast group (large,
      4.40 +/- 0.24 mm; small, 3.52 +/- 0.59 mm) than in the allograft group (large,
      3.82 +/- 0.19 mm; small, 2.57 +/- 0.16 mm). For both graft types (alloplast and
      allograft), the large particle size graft resulted in a greater ridge width gain
      compared with the small particle size graft (P < .05). CONCLUSIONS: Within the
      limitations of the present study, we suggest the use of large particle alloplast
      as the graft material of choice for staged ridge split procedures in the
      posterior mandible.

PMID- 29202264
TI  - Is Augmentation Required to Correct Malar Deficiency With Maxillary Advancement?
AB  - PURPOSE: Patients with maxillary hypoplasia also have malar deficiency;
      therefore, planning can include consideration for simultaneous malar
      augmentation. The purpose of this study was to compare pre- and postoperative
      profiles of patients who underwent Le Fort I advancement, with and without malar
      augmentation, to assess the subjective perception of changes in malar eminence
      projection. MATERIALS AND METHODS: Patients who had maxillary advancement and
      mandibular setback with and without malar augmentation were evaluated through a
      survey consisting of pre- and postoperative photographs that were assessed by
      professionals and laypersons, and a visual analog scale was used to assess the
      malar region. Next, pre- and postoperative images were shown side by side and
      participants were asked to indicate which patients had undergone malar
      augmentation. Statistical analysis used Wilcoxon signed rank test, independent
      samples t test, Spearman rank order correlation, and Mann-Whitney U tests.
      RESULTS: Of 43 patients, 23 met the inclusion criteria and only 7 of the 23
      patients received simultaneous malarplasty. Patients in the 2 groups were
      perceived as having an increase in malar eminence projection postoperatively. In
      the malarplasty and non-malar cohorts, laypersons and professionals noted an
      increase in projection (P < .05). Laypersons tended to overestimate the number of
      malar procedures performed (sensitivity, 59.5%; specificity, 56.8%), whereas
      professionals were better able to accurately exclude malar augmentation
      (sensitivity, 44.2%; specificity, 69.9%). CONCLUSIONS: Most patients with
      maxillary hypoplasia undergoing Le Fort I advancement can expect a subjective
      improvement in malar projection. The decision for malar augmentation at the time
      of maxillary advancement should be considered based on patient desires, but, in
      general, maxillary advancement alone might be sufficient for an optimal malar
      esthetic outcome.

PMID- 29202265
TI  - Kernel Bayesian ART and ARTMAP.
AB  - Adaptive Resonance Theory (ART) is one of the successful approaches to resolving
      "the plasticity-stability dilemma" in neural networks, and its supervised
      learning model called ARTMAP is a powerful tool for classification. Among several
      improvements, such as Fuzzy or Gaussian based models, the state of art model is
      Bayesian based one, while solving the drawbacks of others. However, it is known
      that the Bayesian approach for the high dimensional and a large number of data
      requires high computational cost, and the covariance matrix in likelihood becomes
      unstable. This paper introduces Kernel Bayesian ART (KBA) and ARTMAP (KBAM) by
      integrating Kernel Bayes' Rule (KBR) and Correntropy Induced Metric (CIM) to
      Bayesian ART (BA) and ARTMAP (BAM), respectively, while maintaining the
      properties of BA and BAM. The kernel frameworks in KBA and KBAM are able to avoid
      the curse of dimensionality. In addition, the covariance-free Bayesian
      computation by KBR provides the efficient and stable computational capability to
      KBA and KBAM. Furthermore, Correntropy-based similarity measurement allows
      improving the noise reduction ability even in the high dimensional space. The
      simulation experiments show that KBA performs an outstanding self-organizing
      capability than BA, and KBAM provides the superior classification ability than
      BAM, respectively.

PMID- 29202266
TI  - On-line quantification and human health risk assessment of organic by-products
      from the removal of toluene in air using non-thermal plasma.
AB  - Harmful organic by-products, produced during the removal of volatile organic
      compounds (VOCs) from the air by treatment with non-thermal plasma (NTP), hinder
      the practical applications of NTP. An on-line quantification and risk assessment
      method for the organic by-products produced by the NTP removal of toluene from
      the air has been developed. Formaldehyde, methanol, ketene, acetaldehyde, formic
      acid, acetone, acetic acid, benzene, benzaldehyde, and benzoic acid were
      determined to be the main organic by-products by proton transfer reaction mass
      spectrometry (PTR-MS), a powerful technique for real-time and on-line
      measurements of trace levels of VOCs, and a health-related index (HRI) was
      introduced to assess the health risk of these organic by-products. The discharge
      power (P) is a key factor affecting the formation of the organic by-products and
      their HRI values. Higher P leads to a higher removal efficiency (eta) and lower
      HRI. However, higher P also means higher cost and greater production of discharge
      by-products, such as NOx and O3, which are also very dangerous to the environment
      and human health. In practical applications P, HRI, and eta must be balanced, and
      sometimes the risks posed by the organic by-products are even greater than those
      of the removed compounds. Our mechanistic study reveals that acetone is a crucial
      intermediate for the removal of toluene by NTP, and we found that toluene
      molecules first fragment into acetone molecules, followed by other by-products.
      These observations will guide the study of the mechanism of aromatic molecule
      dissociation in plasma.

PMID- 29202267
TI  - Decrease in male mouse fertility by hydrogen sulfide and/or ammonia can Be
      inheritable.
AB  - Numerous epidemiological studies suggest that air pollutants cause a decline in
      the quality of human spermatozoa and thus a reduction in fertility. However, the
      exact cause of infertility remains unknown. Air pollution gases, such as NH3 and
      H2S are either free or bound to airborne particular materials (PM) and are
      abundant and reactive. The aim of this current investigation was to explore the
      impacts of NH3 and/or H2S on male fertility and the underlying mechanisms. Male
      mouse exposed to H2S and/or NH3 and after two generations were used to evaluate
      the impacts on fertility. The fertility, and spermatozoa quality parameters and
      proteins involved in spermatogenesis were investigated. Our current investigation
      demonstrates: i) H2S and/or NH3 decrease male fertility by 20-30%, reduce the
      spermatozoa concentration about 20-40%, decrease 10-20%, increase around 30%; ii)
      the reduction in male fertility by H2S and/or NH3 can be inheritable; iii) H2S
      and/or NH3 can diminish male fertility through the disruption of spermatogenesis
      without affecting other body parameters such as body weight and organ index. One
      component of air pollutants, for example NH3, does not have a severe impact;
      however, two or more pollutants such as H2S and NH3 combined can cause serious
      health problems, especially with regard to male fertility. We suggest that
      greater attention should be paid to these air pollutants to improve human health
      and fertility.

PMID- 29202268
TI  - Metal(loid) accumulation in aquatic plants of a mining area: Potential for water
      quality biomonitoring and biogeochemical prospecting.
AB  - Aquatic bryophytes can accumulate extremely high levels of chemical elements
      because of their unique morphology and physiology which is markedly different
      from vascular plants. Four aquatic mosses-Fontinalis squamosa, Brachythecium
      rivulare, Platyhypnidium riparioides, Thamnobryum alopecurum-and a freshwater red
      alga Lemanea fluviatilis along with water samples from the streams of Gois mine
      region in Central Portugal were analyzed for 46 elements. Despite being below
      detection levels in the water samples, the elements Zr, V, Cr, Mo, Ru, Os, Rh,
      Ir, Pt, Ag, Ge and Bi were obtained in the plant samples. The moss T. alopecurum
      had the highest mean concentrations of 19 elements followed by B. rivulare (15
      elements). Maximum accumulation of Rb, Ta and Au, however, was seen in the alga
      L. fluviatilis. Bioconcentration factors > 106 were obtained for a few metals.
      The investigation confirms that aquatic bryophytes can be suitable for water
      quality biomonitoring and biogeochemical prospecting in fresh water bodies owing
      to their high accumulative capacity of multi-elements from their aquatic ambient.

PMID- 29202269
TI  - Opportunities and challenges in the use of mineral nutrition for minimizing
      arsenic toxicity and accumulation in rice: A critical review.
AB  - Growing rice on arsenic (As)-contaminated soil or irrigating with As-contaminated
      water leads to significant accumulation of As in grains. Moreover, rice
      accumulates more As into grains than other cereal crops. Thus, rice consumption
      has been identified as a major route of human exposure to As in many countries.
      Inorganic As species are carcinogenic and could pose a considerable health risk
      to humans even at low dietary concentration. Genotypic variation and
      concentration of nutrients such as iron, manganese, phosphate, sulfur and silicon
      are the two main factors that affect As accumulation in rice grains. Therefore,
      in addition to better growth and yield of plants, application of specific
      nutrients in optimum quantities offers an added benefit of decreasing As content
      in rice grains. These nutrient elements influence speciation of As in
      rhizosphere, compete with As for root uptake and interfere with As translocations
      to the shoot and ultimately accumulation in grains. This papers critically
      appraises the methods, forms and rate of application, mechanisms and extent of
      efficiency of different mineral nutrients in decreasing As accumulation in rice
      grains.

PMID- 29202270
TI  - Effects of neuromuscular electrical stimulation on contralateral quadriceps
      function.
AB  - Because maximal voluntary strength of the knee extensor muscles can be
      facilitated by the concomitant application of neuromuscular electrical
      stimulation (NMES) to the contralateral homologous muscle, we aimed to determine
      whether this was associated with an enhanced neural drive to the agonist muscles.
      A secondary goal of this study was to examine the potential dose-response
      relationship between NMES intensity and contralateral facilitation. Twelve
      healthy men (age: 30 +/- 7 yr) completed several maximal voluntary contractions
      (MVC) of the left knee extensors while the right quadriceps received low
      intensity NMES (10% MVC), high-intensity NMES (30% MVC) or no NMES. Supramaximal
      paired stimuli were delivered to the left quadriceps muscle during and
      immediately after the MVCs to assess voluntary activation. The EMG activity of
      vastus lateralis (VL) and biceps femoris (BF) was recorded. MVC torque, voluntary
      activation and VL EMG activity were higher for both low-intensity and high
      intensity NMES compared to no NMES (P < .05), with no difference between the two
      NMES conditions. The acute application of NMES to the right quadriceps
      facilitated MVC strength of the contralateral homonymous muscle by enhancing its
      efferent neural drive. No evident dose-response relationship between NMES
      intensity and contralateral facilitation was observed.

PMID- 29202271
TI  - Microbiota and environmental stress: how pollution affects microbial communities
      in Manila clams.
AB  - Given the crucial role of microbiota in host development, health, and
      environmental interactions, genomic analyses focusing on host-microbiota
      interactions should certainly be considered in the investigation of the adaptive
      mechanisms to environmental stress. Recently, several studies suggested that
      microbiota associated to digestive tract is a key, although still not fully
      understood, player that must be considered to assess the toxicity of
      environmental contaminants. Bacteria-dependent metabolism of xenobiotics may
      indeed modulate the host toxicity. Conversely, environmental variables (including
      pollution) may alter the microbial community and/or its metabolic activity
      leading to host physiological alterations that may contribute to their toxicity.
      Here, 16s rRNA gene amplicon sequencing has been applied to characterize the
      hepatopancreas microbiota composition of the Manila clam, Ruditapes
      philippinarum. The animals were collected in the Venice lagoon area, which is
      subject to different anthropogenic pressures, mainly represented by the
      industrial activities of Porto Marghera (PM). Seasonal and geographic differences
      in clam microbiotas were explored and linked to host response to chemical stress
      identified in a previous study at the transcriptome level, establishing potential
      interactions among hosts, microbes, and environmental parameters. The obtained
      results showed the recurrent presence of putatively detoxifying bacterial taxa in
      PM clams during winter and over-representation of several metabolic pathways
      involved in xenobiotic degradation, which suggested the potential for host
      microbial synergistic detoxifying actions. Strong interaction between seasonal
      and chemically-induced responses was also observed, which partially obscured such
      potentially synergistic actions. Seasonal variables and exposure to toxicants
      were therefore shown to interact and substantially affect clam microbiota, which
      appeared to mirror host response to environmental variation. It is clear that
      understanding how animals respond to chemical stress cannot ignore a key
      component of such response, the microbiota.

PMID- 29202272
TI  - Fish as a model to assess chemical toxicity in bone.
AB  - Environmental toxicology has been expanding as growing concerns on the impact of
      produced and released chemical compounds over the environment and human health
      are being demonstrated. Among the toxic effects observed in organisms exposed to
      pollutants, those affecting skeletal tissues (osteotoxicity) have been somehow
      overlooked in comparison to hepato-, immune-, neuro- and/or reproductive
      toxicities. Nevertheless, sub-lethal effects of toxicants on skeletal development
      and/or bone maintenance may result in impaired growth, reduced survival rate,
      increased disease susceptibility and diminished welfare. Osteotoxicity may occur
      by acute or chronic exposure to different environmental insults. Because of
      biologically and technically advantagous features - easy to breed and inexpensive
      to maintain, external and rapid rate of development, translucent larvae and the
      availability of molecular and genetic tools - the zebrafish (Danio rerio) has
      emerged in the last decade as a vertebrate model system of choice to evaluate
      osteotoxicity. Different experimental approaches in fish species and analytical
      tools have been applied, from in vitro to in vivo systems, from specific to high
      throughput methodologies. Current knowledge on osteotoxicity and underlying
      mechanisms gained using fish, with a special emphasis on zebrafish systems, is
      reviewed here. Osteotoxicants have been classified into four categories according
      to the pathway involved in the transduction of the osteotoxic effects:
      activation/inhibition of membrane and/or nuclear receptors, alteration of redox
      condition, mimicking of bone constituents and unknown pathways. Knowledge on
      these pathways is also reported here as it may provide critical insights into the
      development, production and release of future chemical compounds with none or low
      osteotoxicity, thus promoting the green/environmental friendly chemistry.

PMID- 29202273
TI  - Effects of barley variety, dietary fiber and beta-glucan content on bile acid
      composition in cecum of rats fed low- and high-fat diets.
AB  - Diet-induced obesity and insulin resistance have been linked to changes in bile
      acid (BA) profiles, which in turn are highly dependent on the dietary composition
      and activity of the gut microbiota. The objective of the present study was to
      investigate whether the type and level of fiber had an effect on cecal BA
      composition when included in low- and high-fat diets. Groups of rats were fed two
      barley varieties, which resulted in three test diets containing three levels of
      beta-glucans and two levels of dietary fiber. BAs were preconcentrated using
      hollow fiber liquid-phase microextraction and quantified by gas chromatography.
      The amount of the secondary BAs, lithocholic-, deoxycholic- and hyodexycholic
      acids was generally higher in groups fed high-fat diets compared with
      corresponding acids in groups fed low-fat diets (P<.05). In contrast, most of the
      primary and the secondary BAs, ursodeoxycholic acid and beta- and omega
      muricholic acids, were two to five times higher (P<.05) in groups fed low-fat
      diets than in groups fed high-fat diets. This was particularly true for groups
      fed the highest level of beta-glucans and in some cases also the medium level.
      The BA profile in the gut was strongly dependent on the amount and type of
      dietary fiber in the diet, which may be useful in the prevention/treatment of
      diseases associated with changes in BA profiles.

PMID- 29202275
TI  - Pupil mimicry and trust - Implication for depression.
AB  - Individuals suffering from depression often have difficulty trusting others.
      Previous research has shown a relationship between trust formation and pupil
      mimicry - the synchronization of pupil sizes between individuals. The current
      study therefore examined whether pupil mimicry is weaker in depressed individuals
      and an underlying factor of their low levels of trust. Forty-two patients with
      major depressive disorder (MDD) and 40 healthy control subjects played trust
      games with virtual partners. Images of these partners' eye regions were presented
      to participants before they had to make a monetary investment decision. Partners'
      pupils either dilated, constricted, or remained static over the course of 4-s
      interactions. During the task, participants' pupil sizes were recorded with eye
      tracking equipment to assess mimicry. The results confirm that patients with MDD
      were somewhat less trusting than controls and used another's pupillary cues
      differently when deciding to trust. Specifically, whereas healthy controls
      trusted partners with dilating pupils more than partners with constricting
      pupils, patients with MDD particularly trusted partners whose pupils changed in
      size less, regardless of whether partners' pupils were dilating or constricting.
      This difference in investment behavior was unrelated to differences in pupil
      mimicry, which was equally apparent in both groups and fostered trust to the same
      extent. Whereas lower levels of trust observed in patients with MDD could not be
      explained by differences in pupil mimicry, our data show that pupil dilation
      mimicry might help people to trust. These findings provide further evidence for
      the important role of pupil size and pupil mimicry in interpersonal trust
      formation and shed light on the pathophysiology of clinically low trust in
      patients with MDD.

PMID- 29202274
TI  - Red raspberries suppress NLRP3 inflammasome and attenuate metabolic abnormalities
      in diet-induced obese mice.
AB  - The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical
      role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry
      (RB) contains high amounts of dietary fibers and polyphenolic compounds, which
      are known for their anti-oxidative and anti-inflammatory effects. This study
      evaluated the preventive effects of RB supplementation on the NLRP3 inflammasome
      activation and associated metabolic abnormalities induced by high fat diet (HFD).
      Wild-type male mice (six weeks old) were randomized into 4 groups receiving a
      control or typical western HFD supplemented with or without 5% freeze-dried RB
      for 12 weeks, when mice were sacrificed for tissue collection. HFD feeding
      substantially increased body weight, which was alleviated by RB supplementation
      towards the end of the feeding trial. Dietary RB restored the baseline blood
      glucose level, ameliorating glucose intolerance and insulin resistance, which
      were aggravated by HFD. Additionally, HFD reduced O2 expenditure and CO2
      production, which were ameliorated by RB consumption. The liver is the key site
      for energy metabolism and a key peripheral tissue responsive to insulin. RB
      supplementation reduced hepatic lipid accumulation in HFD mice. In agreement, RB
      consumption suppressed hepatic NLRP3 inflammasome activation and reduced
      interleukin (IL)-1beta and IL-18 production in HFD mice, accompanied with
      normalized mitochondriogenesis. These results suggest that RB consumption
      improves insulin resistance and metabolic dysfunction in diet-induced obesity,
      which is concomitant with suppression of NLRP3 inflammasome elicited by HFD.
      Thus, dietary RB intake is a promising strategy for ameliorating diet-induced
      metabolic abnormalities.

PMID- 29202276
TI  - Academic misconduct - Helping students retain their moral compass.

PMID- 29202277
TI  - Optimizing clobazam treatment in patients with Lennox-Gastaut syndrome.
AB  - Given the complexities managing Lennox-Gastaut syndrome (LGS)-comorbid
      conditions, multiple associated seizure types that tend to be refractory to
      treatment-dosage optimization of antiepileptic drug (AED) treatment is a
      challenge. In the absence of clinical trial data on optimization of AED dosage in
      patients with LGS, dose titration is guided by personal experience, anecdotal
      evidence, and specific patient factors (age, comorbid conditions and medications,
      seizure types, etc.). The goal of this study was to determine whether a 20%
      increase in adjunctive clobazam was a reasonable benchmark for improved seizure
      response in patients with LGS who had responded to adjunctive clobazam treatment
      during a 12-week lead-in trial. This was a post hoc analysis of data from a long
      term, open-label extension (OLE) study, which comprised patients who completed 1
      of 2 pivotal clobazam lead-in studies. During the lead-in studies, patients
      received either placebo or clobazam (0.25, 0.50, or 1.0mg/kg/d) (maximum 40mg/d);
      during OLE, patients received clobazam up to 2.0mg/kg/d (maximum 80mg/d). The
      post hoc analysis population comprised patients who had >=25%, >=50%, or >=75%
      seizure reduction from baseline during lead-in clobazam treatment and >=12months
      of follow-up data during OLE. Successful dosage increase (i.e., dosage
      optimization) was defined as >=20% clobazam dosage increase from OLE baseline,
      and improved seizure control from OLE baseline (improvement in seizure responder
      status, or >50% reduction in total seizure frequency). Patients were stratified
      by responder status after lead-in treatment (OLE baseline) and by lead-in
      clobazam dosage received. The findings of the analysis indicated that clobazam
      dosage increases of >=20% during long-term treatment improved seizure control
      >80% of patients with LGS who responded to clobazam during lead-in treatment.
      Rates of successful dosage increase during OLE were high regardless of lead-in
      dosage received, with the highest rate of successful dosage increase among
      patients who received low-dosage clobazam during lead-in. Similarly, rates of
      successful dose increase were high regardless of lead-in seizure responder
      category, with the highest rates occurring in patients with the highest (>=75%)
      lead-in response.

PMID- 29202278
TI  - Treatment Outcomes of 257 Patients with Locoregionally Advanced Nasopharyngeal
      Carcinoma Treated with Nimotuzumab Plus Intensity-Modulated Radiotherapy with or
      without Chemotherapy: A Single-Institution Experience.
AB  - OBJECTIVES: To report the long-term outcome and toxicity of locoregionally
      advanced nasopharyngeal carcinoma (LA NPC) treated with nimotuzumab (h-R3) plus
      intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS:
      From May 2008 to March 2014, 3022 newly histology-proven, nonmetastatic NPC
      patients were retrospectively reviewed; among them, 257 patients treated with h
      R3 were enrolled in this study. The patients' age range was between 10 and 76
      years. The distribution of patients by disease stage was 150 (58.4%) in stage
      III, 88 (34.2%) in stage IV A, and 19 (7.4%) in stage IV B. All the patients
      received the treatment of h-R3 plus IMRT, and from them, 239 cases were also
      treated with cisplatin-based chemotherapy. Acute and late radiation-related
      toxicities were graded according to the Acute and Late Radiation Morbidity
      Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival
      was calculated according to the Kaplan-Meier method. Log-rank test was used to
      compare the survival difference. Multivariate analysis was performed using Cox's
      proportional-hazard model. RESULTS: All 257 patients had completed combined
      treatment; 231 patients received h-R3 plus IMRT with induction chemotherapy (IC),
      while 26 patients received only h-R3 plus IMRT. With a median follow-up of 48
      months (range, 13-75 months), the estimated 5-year local recurrence-free
      survival, regional recurrence-free survival, distant metastases-free survival,
      progression-free survival, and overall survival (OS) rates were 94.3%, 94.8%,
      91.9%, 83.4%, and 86.2%, respectively. Univariate analysis showed that age, T
      stage, clinical stage, and IC were related with OS. Multivariate analysis
      indicated that T stage and IC were independent prognostic factors for OS. The
      incidence of grade 3 to 4 acute mucositis and leukocytopenia was 10.9% and 19.8%,
      respectively, with no cases of skin rash and infusion reaction. Xerostomia was
      the most common late complication, and the degree of dry mouth in most survivors
      was mild to moderate at the last follow-up time. CONCLUSION: h-R3 plus IMRT with
      or without chemotherapy showed promising outcomes in terms of locoregional
      control and survival without increasing the incidence of radiation-related
      toxicities for patients.

PMID- 29202279
TI  - Cancer-Specific Inhibitory Effects of Genetically Engineered Stem Cells
      Expressing Cytosine Deaminase and Interferon-beta Against Choriocarcinoma in
      Xenografted Metastatic Mouse Models.
AB  - Cancer treatments using stem cells expressing therapeutic genes have been
      identified for various types of cancers. In this study, we investigated
      inhibitory effects of HB1.F3.CD and HB1.F3.CD.IFN-beta cells expressing
      Escherichia coli cytosine deaminase (CD) and human interferon-beta (IFN-beta)
      genes in intravenously (i.v.) injected mice with a metastasis model. In this
      treatment, pro-drug 5-fluorocytosine (5-FC) is converted to cytotoxic drug 5
      fluorouracil by hNSCs expressing the CD gene, which inhibits DNA synthesis in
      cancer cells. Moreover, IFN-beta induces apoptosis and reduces the growth of
      cancer cells. Upon MTT assay, proliferation of choriocarcinoma (JEG-3) cells
      decreased when co-cultured with hNSCs expressing CD and IFN-beta genes. To
      confirm the cancer-tropic effect of these stem cells, chemoattractant factors
      (VEGF, CXCR4, and C-kit) secreted from JEG-3 cells were identified by polymerase
      chain reaction. hNSCs migrate toward JEG-3 cells due to ligand-receptor
      interactions of these factors. Accordingly, the migration capability of hNSCs
      toward JEG-3 cells was confirmed using an in vitro Trans-well assay, in vivo
      subcutaneously (s.c.) injected mice groups (xenograft model), and metastasis
      model. Intravenously injected hNSCs migrated freely to other organs when compared
      to s.c. injected hNSCs. Thus, we confirmed the inhibition of lung and ovarian
      metastasis of choriocarcinoma by i.v. injected HB1.F3.CD or HB1.F3.CD.IFN-beta
      cells in the presence of 5-FC. Treatment of these stem cells also increased the
      survival rates of mice. In conclusion, this study showed that metastatic cancer
      was diminished by genetically engineered hNSCs and noncytotoxic drug 5-FC. This
      is the first report of the therapeutic potential of i.v. injected hNSCs in a
      metastasis model; therefore, the results indicate that this stem cell therapy can
      be used as an alternative novel tool to treat metastatic choriocarcinoma.

PMID- 29202280
TI  - No evidence for common processes of cognitive control and self-control.
AB  - Cognitive control and self-control are often used as interchangeable terms. Both
      terms refer to the ability to pursue long-term goals, but the types of controlled
      behavior that are typically associated with these terms differ, at least
      superficially. Cognitive control is observed in the control of attention and the
      overcoming of habitual responses, while self-control is observed in resistance to
      short-term impulses and temptations. Evidence from clinical studies and
      neuroimaging studies suggests that below these superficial differences, common
      control process (e.g., inhibition) might guide both types of controlled behavior.
      Here, we study this hypothesis in a behavioral experiment, which interlaced
      trials of a Simon task with trials of an intertemporal decision task. If
      cognitive control and self-control depend on a common control process, we
      expected conflict adaptation from Simon task trials to lead to increased self
      control in the intertemporal decision trials. However, despite successful
      manipulations of conflict and conflict adaptation, we found no evidence for this
      hypothesis. We investigate a number of alternative explanations of this result
      and conclude that the differences between cognitive control and self-control are
      not superficial, but rather reflect differences at the process level.

PMID- 29202281
TI  - Structure and properties of epoxy-siloxane-silica nanocomposite coatings for
      corrosion protection.
AB  - HYPOTHESIS: The fraction of the silica/siloxane phase is a crucial parameter,
      which determines the structure and thus the properties of epoxy-siloxane-silica
      hybrid coatings. A careful adjustment of the colloidal precursor formulation
      allows tuning the nanostructure towards a highly condensed and cross-linked
      hybrid nanocomposite, suitable as an efficient anticorrosive coating.
      EXPERIMENTS: Novel epoxy-siloxane-silica hybrids have been prepared through the
      curing reaction of poly(bisphenol A-co-epichlorohydrin) (DGEBA) with
      diethyltriamine (DETA) and (3-glycidoxypropyl)methyltriethoxysilane (GPTMS),
      followed by hydrolytic condensation of tetraethoxysilane (TEOS) and GPTMS. At a
      constant proportion of the organic phase, the effects of the varying molar
      proportions of siloxane (GPTMS) and silica (TEOS) on the film properties have
      been investigated. FINDINGS: A detailed structural analysis suggests for
      intermediate TEOS to GPTMS ratios a structure of highly condensed silica-siloxane
      domains covalently bonded to the embedding epoxy phase. The homogeneous
      distribution of the quasi-spherical sub-nonmetric silica-siloxane nodes is in
      agreement with low surface roughness (<5 nm), observed by atomic force
      microscopy. This dense nanostructure results in high thermal stability (>300 
      degrees C), strong adhesion to steel substrate and excellent barrier property in
      saline solution, with corrosion resistance in the GOmega cm2 range.

PMID- 29202282
TI  - Treatment of heavy metal polluted industrial wastewater by a new water treatment
      process: ballasted electroflocculation.
AB  - This laboratory study investigated the parameters efficiency of the new
      technology: ballasted electro-flocculation (BEF) using aluminum (Al) electrodes
      to remove cadmium and zinc from industrial mining wastewater (MWW). The principle
      of the BEF process is based on the use of micro-sand and polymer together to
      increase the weight of the flocs and the rate at which they settle is radically
      changing the electrocoagulation-electroflocculation settling methodology. Based
      on the examination of the operation parameters one by one, the best removal
      percentage was obtained at a current intensity of 2A, a the flow rate of 20L/h, a
      micro-sand dose of 6g/L, a polyethyleneimine (PEI) polymer dose of 100mg, the
      contact times of 30min, a stirring speed of 50 RPM, a monopolar configuration of
      the electrodes, and an electrodes number of 10. The results showed that the flow
      rate and the current density have a preponderant effect on the variability of the
      quality of the settled water. In comparison, filterability was found to be more
      sensitive to number of electrodes, micro sand dosages and current density. It was
      dependent on the ratio of microsand to PEI polymer dosage, and improved when this
      ratio increased. Response surface methodology was applied to evaluate the main
      effects and interactions among stirring speed, polymer dose, current intensity,
      and electrodes number. The removal of Cd and Zn from industrial MWW was done for
      very low cost of 0.1TND/m3 equivalent to 0.04?/m3. The investigation of BEF
      process proposes a highly cost-effective wastewater treatment method if compared
      to Actiflo TM and electrocoagulation.

PMID- 29202283
TI  - Brominated flame retardants and toxic elements in the meat and liver of red deer
      (Cervus elaphus), wild boar (Sus scrofa), and moose (Alces alces) from Latvian
      wildlife.
AB  - In order to evaluate the contamination status of terrestrial biota in Latvia,
      muscle and liver tissues of red deer (Cervus elaphus), wild boar (Sus scrofa),
      and moose (Alces alces) were analyzed for the content of polybrominated diphenyl
      ethers (PBDE), hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA), as
      well as cadmium and lead. The highest mean concentrations of PBDEs (46.6pgg-1 wet
      weight (w.w.)), cadmium (0.95mgkg-1 w.w.), and lead (0.22mgkg-1 w.w.) were
      observed in the tissues of moose, while the wild boar samples contained the
      highest levels of HBCD, with the mean concentration equal to 264pgg-1 w.w. in
      muscle tissues. Generally low mean concentrations of TBBPA from 0.52 to 4.54pgg-1
      w.w. were observed. The liver tissue of all analyzed specimens was found to
      contain higher concentrations of contaminants, compared to muscle tissue. The
      congener profile of PBDEs in the analyzed tissues indicated that the recently
      used "penta-BDE" formulation was a probable source, while components of HBCD,
      "octa-BDE", and "deca-BDE" technical mixtures are likely to undergo congener
      specific or diastereomer-specific bioaccumulation or metabolic degradation.
      Considering the reports from other regions, it can be concluded that the
      terrestrial biota in Latvia is less affected by the studied contaminants.

PMID- 29202284
TI  - Recent evolution of 129I levels in the Nordic Seas and the North Atlantic Ocean.
AB  - Most of the anthropogenic radionuclide 129I released to the marine environment
      from the nuclear fuel reprocessing plants (NFRP) at Sellafield (England) and La
      Hague (France) is transported to the Arctic Ocean via the North Atlantic Current
      and the Norwegian Coastal Current. 129I concentrations in seawater provides a
      powerful and well-established radiotracer technique to provide information about
      the mechanisms which govern water mass transport in the Nordic Seas and the
      Arctic Ocean and is gaining importance when coupled with other tracers (e.g. CFC,
      236U). In this work, 129I concentrations in surface and depth profiles from the
      Nordic Seas and the North Atlantic (NA) Ocean collected from four different
      cruises between 2011 and 2012 are presented. This work allowed us to i) update
      information on 129I concentrations in these areas, required for the accurate use
      of 129I as a tracer of water masses; and ii) investigate the formation of deep
      water currents in the eastern part of the Nordic Seas, by the analysis of 129I
      concentrations and temperature-salinity (T-S) diagrams from locations within the
      Greenland Sea Gyre. In the Nordic Seas, 129I concentrations in seawater are of
      the order of 109 at.kg-1, one or two orders of magnitude higher than those
      measured at the NA Ocean, not so importantly affected by the releases from the
      NFRP. 129I concentrations of the order of 108atoms.kg-1 at the Ellet Line and the
      PAP suggest a direct contribution from the NFRP in the NA Ocean. An increase in
      the concentrations in the Nordic Seas between 2002 and 2012 has been detected,
      which agrees with the temporal evolution of the 129I liquid discharges from the
      NFRPs in years prior to this. Finally, 129I profile concentrations, 129I
      inventories and T-S diagrams suggest that deep water formation occurred in the
      easternmost area of the Nordic Seas during 2012.

PMID- 29202285
TI  - A historical perspective on soil organic carbon in Mediterranean cropland (Spain,
      1900-2008).
AB  - Soil organic carbon (SOC) management is key for soil fertility and for mitigation
      and adaptation to climate change, particularly in desertification-prone areas
      such as Mediterranean croplands. Industrialization and global change processes
      affect SOC dynamics in multiple, often opposing, ways. Here we present a detailed
      SOC balance in Spanish cropland from 1900 to 2008, as a model of a Mediterranean,
      industrialized agriculture. Net Primary Productivity (NPP) and soil C inputs were
      estimated based on yield and management data. Changes in SOC stocks were modeled
      using HSOC, a simple model with one inert and two active C pools, which combines
      RothC model parameters with humification coefficients. Crop yields increased by
      227% during the studied period, but total C exported from the agroecosystem only
      increased by 73%, total NPP by 30%, and soil C inputs by 20%. There was a
      continued decline in SOC during the 20th century, and cropland SOC levels in 2008
      were 17% below their 1933 peak. SOC trends were driven by historical changes in
      land uses, management practices and climate. Cropland expansion was the main
      driver of SOC loss until mid-20th century, followed by the decline in soil C
      inputs during the fast agricultural industrialization starting in the 1950s,
      which reduced harvest indices and weed biomass production, particularly in woody
      cropping systems. C inputs started recovering in the 1980s, mainly through
      increasing crop residue return. The upward trend in SOC mineralization rates was
      an increasingly important driver of SOC losses, triggered by irrigation
      expansion, soil cover loss and climate change-driven temperature rise.

PMID- 29202286
TI  - PM10 concentration forecasting in the metropolitan area of Oviedo (Northern
      Spain) using models based on SVM, MLP, VARMA and ARIMA: A case study.
AB  - Atmospheric particulate matter (PM) is one of the pollutants that may have a
      significant impact on human health. Data collected over seven years in a city of
      the north of Spain is analyzed using four different mathematical models: vector
      autoregressive moving-average (VARMA), autoregressive integrated moving-average
      (ARIMA), multilayer perceptron (MLP) neural networks and support vector machines
      (SVMs) with regression. Measured monthly average pollutants and PM10 (particles
      with a diameter less than 10MUm) concentration are used as input to forecast the
      monthly averaged concentration of PM10 from one to seven months ahead.
      Simulations showed that the SVM model performs better than the other models when
      forecasting one month ahead and also for the following seven months.

PMID- 29202287
TI  - Combined use of geophysical and geochemical methods to assess areas of active,
      degrading and restored blanket bog.
AB  - Here we combine the use of geo-electrical techniques with geochemical analysis of
      the solid and liquid phase to determine subsurface properties and general
      peatland health. Active, degrading and restored peat locations were analysed from
      the same blanket bog site (ensuring they were under the same environmental
      conditions, such as rainfall and temperature) at the Garron Plateau, Northern
      Ireland. A normalized chargeability (ratio of resistivity (inverse of
      conductivity) and chargeability) profile was compared with organic composition
      analysis of the solid and liquid phases from active, degrading and restored
      locations. Results show that the degrading location is undergoing high rates of
      decomposition and loss of organic matter into the interstitial water, whereas the
      opposite is true for the active location. The restored peat is showing low rates
      of decomposition however has a high concentration of organic material in the
      porewater, primarily composing long chain aliphatic compounds, sourced from
      vascular plants. The ingression of vascular plants permits the diffusion of
      oxygen via roots into the subsurface and supports the oxidation of phenols by
      phenol oxidase, which produces phenoxy radicals and quinones (CO double bonds).
      This production of conjugated quinones, which are characterized by a CO double
      bond, in the aerated degrading and restored locations, increase the polarity,
      cation exchange capacity, and the normalized chargeability of the peat. This
      higher chargeability is not evident in the active peat due to decreased aerobic
      decomposition and a domination of sphagnum mosses.

PMID- 29202288
TI  - Role of chelant on Cu distribution and speciation in Lolium multiflorum by
      synchrotron techniques.
AB  - Chelants are known to enhance metal translocation in plants; however, the
      underlying mechanisms are still not fully understood. This study aimed to
      elucidate the distribution and speciation of Cu in ryegrass (Lolium multiflorum)
      in both absence and presence of the biodegradable chelant [S,S']-ethylenediamine
      disuccinic acid (EDDS). The results showed that EDDS increased the Cu
      translocation factor from root to shoot by 6-9 folds under CuEDDS in comparison
      with free Cu (50-250MUM). Synchrotron-based microscopic X-ray fluorescence (MU
      XRF) mapping revealed that EDDS alleviated Cu deposition in the root meristem of
      root apex and the junction of lateral root zone, and facilitated Cu transport to
      root stele for subsequent translocation upwards. X-ray absorption near edge
      structure (XANES) analysis found that free Cu was sequestered in plants as a
      mixture of Cu-organic ligands. In the EDDS treatment, Cu was primarily present as
      CuEDDS (49-67%) in plants with partial chemical transformation to Cu-histidine
      (21-36%) and Cu(I)-glutathione (0-24%). These results suggest that EDDS improves
      internal Cu mobility through forming CuEDDS, thus decreasing the root
      sequestration of Cu, and ultimately facilitating Cu transport to plant shoots.

PMID- 29202289
TI  - Concentrating mixtures of neuroactive pharmaceuticals and altered
      neurotransmitter levels in the brain of fish exposed to a wastewater effluent.
AB  - Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent
      discharges from wastewater treatment plants and concerns have arisen regarding
      their potential impacts on fish behaviour and ecology. In this study, we
      investigated the uptake of 14 neuroactive pharmaceuticals from a treated
      wastewater effluent into blood plasma and brain regions of roach (Rutilus
      rutilus) after exposure for 15days. We show that a complex mixture of
      pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin
      noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic
      antidepressants and a benzodiazepine, concentrate in different regions of the
      brain including the telencephalon, hypothalamus, optic tectum and hindbrain of
      effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were
      between 3-40 fold higher in brain compared with blood plasma, showing these
      neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for
      the potential for any adverse ecotoxicological effects, the effect ratio was
      calculated from human therapeutic plasma concentrations (HtPCs) and the measured
      or predicted fish plasma concentrations of pharmaceuticals. After accounting for
      a safety factor of 1000, the effect ratios indicated that fluoxetine,
      norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk
      assessment studies. Furthermore, although plasma concentrations of all the
      pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in
      serotonin, glutamate, acetylcholine and tryptophan concentrations were observed
      in different brain regions of effluent-exposed fish. This study highlights the
      importance of determining the potential health effects arising from the
      concentration of complex environmental mixtures in risk assessment studies.

PMID- 29202290
TI  - Insights about the toxic effects of tannery effluent on Lithobates catesbeianus
      tadpoles.
AB  - Tannery industries are considered highly polluting due to the large production of
      polluted wastewater [untreated tannery effluent (UTE)]. Although previous studies
      have already shown the consequences from fish, birds and mammals' exposure to
      this pollutant, little is known about its toxicological effect on representatives
      of class amphibian. Thus, we aim at assessing whether short-term UTE exposure,
      even at low concentrations (0.2% UTE diluted in water), would be able to induce
      behavioral, morphological and cyto-genotoxic changes in L. catesbeianus tadpoles.
      In order to do so, two experimental groups were set (control and tannery
      effluent) and exposed, or not, to UTE for seven days. A positive control group
      (cyclophosphamide) was included in the experimental design in order to assess
      cyto-genotoxicity. Our behavioral results showed that tadpoles exposed to the
      contaminant presented abnormal responses in the predator-response test;
      therefore, it evidenced losses in their capacity to recognize chemical olfactory
      cues of a potential predator. We also searched for changes in mouth length, in
      dentition, in body length before and after the eyes of animals exposed to UTE.
      Besides, we observed higher nuclear abnormality frequency in the circulating
      erythrocytes of tadpoles exposed to the contaminant, as well as in animals
      belonging to the positive control group. Some of the observed abnormalities were
      micronuclei, binucleated, notched, kidney-shaped and blebbed cells,
      multilobulated nuclei, as well as lower mitotic index. Therefore, our data
      confirm the hypothesis that UTE causes behavioral, morphological and cyto
      genotoxic changes in L. catesbeianus tadpoles, fact that opens new perspectives
      to other investigations about how and which UTE constituents were responsible for
      the observed effects.

PMID- 29202292
TI  - Letter to the editor, TiO2 nanoparticles in the marine environment: Impact on the
      toxicity of phenanthrene and Cd2+ to marine zooplankton Artemia salina.

PMID- 29202291
TI  - Modeling the effects of climatic and land use changes on phytoplankton and water
      quality of the largest Turkish freshwater lake: Lake Beysehir.
AB  - Climate change and intense land use practices are the main threats to ecosystem
      structure and services of Mediterranean lakes. Therefore, it is essential to
      predict the future changes and develop mitigation measures to combat such
      pressures. In this study, Lake Beysehir, the largest freshwater lake in the
      Mediterranean basin, was selected to study the impacts of climate change and
      various land use scenarios on the ecosystem dynamics of Mediterranean freshwater
      ecosystems and the services that they provide. For this purpose, we linked
      catchment model outputs to the two different processed-based lake models: PCLake
      and GLM-AED, and tested the scenarios of five General Circulation Models, two
      Representation Concentration Pathways and three different land use scenarios,
      which enable us to consider the various sources of uncertainty. Climate change
      and land use scenarios generally predicted strong future decreases in hydraulic
      and nutrient loads from the catchment to the lake. These changes in loads
      translated into alterations in water level as well as minor changes in
      chlorophyll a (Chl-a) concentrations. We also observed an increased abundance of
      cyanobacteria in both lake models. Total phosphorus, temperature and hydraulic
      loading were found to be the most important variables determining cyanobacteria
      biomass. As the future scenarios revealed only minor changes in Chl-a due to the
      significant decrease in nutrient loads, our results highlight that reduced
      nutrient loading in a warming world may play a crucial role in offsetting the
      effects of temperature on phytoplankton growth. However, our results also showed
      increased abundance of cyanobacteria in the future may threaten ecosystem
      integrity and may limit drinking water ecosystem services. In addition, extended
      periods of decreased hydraulic loads from the catchment and increased evaporation
      may lead to water level reductions and may diminish the ecosystem services of the
      lake as a water supply for irrigation and drinking water.

PMID- 29202293
TI  - Sulfur-modified rice husk biochar: A green method for the remediation of mercury
      contaminated soil.
AB  - Mercury (Hg) contamination of surface soils has increased by ~86Giga grams due to
      anthropogenic activities. There is an urgent need to find new, effective and
      preferably 'green' remediation technologies to protect human health and the
      environment. Sulfur-modification of sorbents can greatly enhance Hg sorption
      capacity - by forming low solubility HgS (cinnabar). However, S-modified sorbents
      are not considered suitable for soil remediation due to the economic cost and
      secondary environmental impacts of sorbents such as granulated activated carbon
      (GAC), and the toxicity of S-modifiers such as thiol compounds. It was previously
      found that if biochar is used as an alternative to GAC then the overall
      environmental impact can be significantly reduced. However, due to a lack of
      experimental evidence, the practicality of S-modified biochar remains uncertain.
      The present study was undertaken to provide a proof-of-concept for the 'green'
      remediation of Hg contaminated soils with rice husk biochar modified with non
      toxic elemental S. It was found that the S modification process increased the
      biochar S content from 0.2% to 13.04% via surface deposition or volume pore
      filling. This increased the biochar's Hg2+ adsorptive capacity (Qmax) by ~73%, to
      67.11mg/g. To assess the performance of S-modified rice husk biochar for soil
      remediation it was applied to a high 1000mg/kg Hg2+ contaminated soil. Treatment
      dosages of 1%, 2% and 5% (dry wt.) were found to reduce freely available Hg in
      TCLP (toxicity characterization leaching procedure) leachates by 95.4%, 97.4% and
      99.3%, respectively, compared to untreated soil. In comparison, unmodified rice
      husk biochar reduced Hg concentrations by 94.9%, 94.9% and 95.2% when applied at
      the same treatment dosage rates, respectively. This study has revealed that S
      modified rice husk biochar has potential to stabilize Hg as a 'green' method for
      the remediation of contaminated soils.

PMID- 29202294
TI  - Comparative live-imaging of in vivo EROD (ethoxyresorufin-O-deethylase) induction
      in zebrafish (Danio rerio) and fathead minnow (Pimephales promelas) embryos after
      exposure to PAHs and river sediment extracts.
AB  - The measurement of EROD (ethoxyresorufin-O-deethylase) activity to determine the
      induction of CYP1A after exposure to dioxin-like substances is a well-established
      biomarker in fish. For reasons of animal welfare and implementations of new
      chemicals regulations (REACh), in vivo methods using zebrafish (Danio rerio) and
      medaka (Oryzias latipes) embryos have recently been developed to quantify CYP1A
      induction, which is visualized as mean intensity of the autofluorescent resorufin
      formed in living anaesthetized embryos. In the present study, concentration
      ranges of three PAHs (benzo[a]pyrene, beta-naphthoflavone, benzo[k]fluoranthene)
      as examples of known CYP1A inducers as well as extracts of two well-characterized
      sediment samples of the lower Neckar river (Southern Germany) were used to
      determine the suitability of the fathead minnow (Pimephales promelas) embryo for
      the in vivo EROD assay. Data for zebrafish embryos were generated for comparison.
      Fathead minnow embryos were principally suitable to show in vivo EROD induction
      via live-imaging. Since in fathead minnow embryos both signal area and
      fluorescence intensities are lower than in zebrafish embryos, the induction
      potentials of the three model PAHs and the environmental samples proved to be
      species-dependent. Among the three PAHs tested, benzo[k]fluoranthene lead to the
      strongest EROD signal followed by beta-naphthoflavone and benzo[a]pyrene in
      comparison to the positive control. Whereas benzo[k]fluoranthene and beta
      naphthoflavone showed a dose-response relationship for the EROD induction,
      benzo[a]pyrene failed to induce a significant signal in fathead minnow embryos.
      If compared to the model PAHs, the extracts of both sediments from the lower
      Neckar River induced stronger EROD signals in both fathead minnow and zebrafish
      embryos. Observations thus documented fathead minnow embryos to be as suitable
      for biomonitoring purposes as are zebrafish embryos.

PMID- 29202295
TI  - Constitutive MAP-kinase activation suppresses germline apoptosis in NTH-1 DNA
      glycosylase deficient C. elegans.
AB  - Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires
      the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a
      well-established model to study phenotypic consequences and cellular responses to
      oxidative stress. To better understand how BER affects phenotypes associated with
      oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the
      only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1
      DNA glycosylase. We show that nth-1 mutants have mitochondrial dysfunction
      characterised by lower mitochondrial DNA copy number, reduced mitochondrial
      membrane potential, and increased steady-state levels of reactive oxygen species.
      Consistently, nth-1 mutants express markers of chronic oxidative stress with high
      basal phosphorylation of MAP-kinases (MAPK) but further activation of MAPK in
      response to the superoxide generator paraquat is attenuated. Surprisingly, nth-1
      mutants also failed to induce apoptosis in response to paraquat. The ability to
      induce apoptosis in response to paraquat was regained when basal MAPK activation
      was restored to wild type levels. In conclusion, the failure of nth-1 mutants to
      induce apoptosis in response to paraquat is not a direct effect of the DNA repair
      deficiency but an indirect consequence of the compensatory cellular stress
      response that includes MAPK activation.

PMID- 29202296
TI  - A performance study on three qPCR quantification kits and their compatibilities
      with the 6-dye DNA profiling systems.
AB  - DNA quantification plays an integral role in forensic DNA profiling. Not only
      does it estimate the total amount of amplifiable human autosomal and male DNA to
      ensure optimal amplification of target DNA for subsequent analysis, but also
      assesses the extraction efficiency and purity of the DNA extract. Latest DNA
      quantification systems even offer an estimate for the degree of DNA degradation
      in a sample. Here, we report the performance of three new generation qPCR kits,
      namely Investigator(r) Quantiplex HYres Kit from QIAGEN, Quantifiler(r) Trio DNA
      Quantification Kit from Applied BiosystemsTM, and PowerQuant(r) System from
      Promega, and their compatibilities with three 6-dye DNA profiling systems. Our
      results have demonstrated that all three kits generate standard curves with
      satisfactory consistency and reproducibility, and are capable of screening out
      traces of male DNA in the presence of 30-fold excess of female DNA. They also
      exhibit a higher tolerance to PCR inhibition than Quantifiler(r) Human DNA
      Quantification Kit from Applied BiosystemsTM in autosomal DNA quantification.
      PowerQuant(r), as compared to Quantiplex HYres and Quantifiler(r) Trio, shows a
      better precision for both autosomal and male DNA quantifications. Quantifiler(r)
      Trio and PowerQuant(r) in contrast to Quantiplex HYres offer better correlations
      with lower discrepancies between autosomal and male DNA quantification, and their
      additional degradation index features provide a detection platform for inhibited
      and/or degraded DNA template. Regarding the compatibility between these
      quantification and profiling systems: (1) both Quantifiler(r) Trio and
      PowerQuant(r) work well with GlobalFiler and Fusion 6C, allowing a fairly
      accurate prediction of their DNA typing results based on the quantification
      values; (2) Quantiplex HYres offers a fairly reliable IPC system for detecting
      any potential inhibitions on Investigator 24plex, whereas Quantifiler(r) Trio and
      PowerQuant(r) suit better for GlobalFiler and Fusion 6C.

PMID- 29202297
TI  - Finite element investigation of the effect of nucleus removal on vibration
      characteristics of the lumbar spine under a compressive follower preload.
AB  - Previous studies have reported the effect of removing the nucleus on
      biomechanical responses of the human spine to static loadings. However, few
      studies have dealt with the whole-body vibration condition. The purpose of this
      study was to investigate the effect of a single-level (L4-L5) nucleus removal on
      vibration characteristics of the whole lumbar spine in the presence of a
      physiologic compressive preload, and also to evaluate the preload effect on the
      vibration characteristics. A 3-D non-linear finite element model of the lumbar
      spine (L1 to sacrum) subjected to the physiologic conditions of a compressive
      follower preload was developed and validated. Comparative studies on forced
      vibration responses between the intact and denucleated models were conducted. The
      results from the forced-vibration (transient dynamic) analyses considering axial
      cyclic loading indicated that the nucleus removal increased the dynamic responses
      at all disc levels. For example, at the denucleated L4-L5 level, after nucleus
      removal the maximum response values of disc bulge and von-Mises stress in annulus
      increased by 63.9% and 110.5% respectively, and their vibration amplitudes
      increased by 97.9% and 139.7% respectively. At other levels, the predicted
      maximum response values and vibration amplitudes of the stresses and strains also
      produced 3.1-7.5% and 10.8-30.6% increases respectively due to the nucleus
      removal, and a relatively larger increase was observed at level L5-S1. It was
      also found that increasing the preload increased the stresses and strains at all
      levels but decreased their vibration amplitudes. Nucleus removal at a single
      level deteriorates the effects of vibration on whole lumbar spine. Also,
      increasing the preload alters vibration characteristics of the spine. These
      findings may be useful to provide a guideline for the patients suffering from
      lumbar disc degeneration to minimize the risk of further injury and discomfort.

PMID- 29202298
TI  - Impact of pH and application time of meta-phosphoric acid on resin-enamel and
      resin-dentin bonding.
AB  - PURPOSE: To evaluate the immediate microshear resin-enamel bond strength (MUSBS)
      and the immediate and 6-month microtensile bond strength (MUTBS) and nanoleakage
      (NL) of the adhesive interface performed by different pHs of 40% meta-phosphoric
      acid (MPA) were compared with conventional 37% ortho-phosphoric acid (OPA) under
      different application times. Additionally, the enamel etching patterns were
      evaluated and the chemical/morphological changes induced by these differents
      groups were evaluated. MATERIALS AND METHODS: One hundred and ninety-eight
      extracted human molars were randomly assigned into experimental groups according
      to the combination of independent variables: Acid [37% ortho-phosphoric acid
      (OPA), 40% meta-phosphoric acid (MPA) at pHs of: 0.5, 1 and 2] and Application
      Time [7, 15 and 30s]. Enamel-bond specimens were prepared and tested under MUSBS.
      Resin-dentin beams were tested under MUTBS tested immediately or after 6-months
      of water storage. Nanoleakage was evaluated using bonded-beams of each tooth/time
      period. Enamel etching pattern and chemical and ultra-morphology analyses were
      also performed. The MUSBS (MPa) data were subjected to a two-way repeated
      measures ANOVA (Acid vs. Application time). For MUTBS, Acid vs application time
      vs storage time data were subjected to three-way ANOVA and Tukey's test (alpha =
      0.05). RESULTS: MPA pH 0.5 showed MUTBS similar to OPA, independently of the
      application time on enamel (p>0.05) or dentin (p>0.05). OPA provided higher
      nanoleakage values than MPA (p = 0.003). Significant decreases in TBS and
      increases in NL were only observed for OPA after 6 months (p = 0.001). An
      increase in the application time resulted in a more pronounced etching pattern
      for MPA. Chemical analysis showed that dentin demineralized by MPA depicted peaks
      of brushite and octacalcium phosphate. MPA exposed less collagen than OPA.
      However, optimal results for MPA were dependent on pH/application time.
      CONCLUSION: The use of 40% meta-phosphoric acid with a pH of 0.5 is an
      alternative acid-etching agent for dentin and enamel bonding. Furthermore, the
      use of MPA preserves the resin-dentin interface over a 6-months period, due to
      presence of brushite and octacalcium phosphate and a reduced demineralization
      pattern.

PMID- 29202299
TI  - Repression of interferon beta-regulated cytokines by the JAK1/2 inhibitor
      ruxolitinib in inflammatory human macrophages.
AB  - Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor, currently used in the
      treatment of myeloproliferative neoplasms. It exerts potent anti-inflammatory
      activity, but the involved molecular and cellular mechanisms remain poorly
      understood. In order to gain insights about this point, ruxolitinib effects
      towards expression of main inflammatory cytokines were studied in human
      macrophages, which constitute a key-cell type implicated in inflammation.
      Analysis of mRNA expression of cytokines (n=84) by PCR array indicated that,
      among those induced by the pro-inflammatory stimulus lipopolysaccharide (LPS)
      (n=44), 61.4% (n=27) were repressed by 5MUM ruxolitinib. The major inflammatory
      cytokines, interleukin (IL) 6 and tumor necrosis factor alpha, were notably down
      regulated by ruxolitinib at both the mRNA and protein level. Other repressed
      cytokines included IL27 and the chemokines CCL2, CXCL9, CXCL10 and CXCL11, but
      not IL1beta. The interferon (IFN) beta/JAK/signal transducer and activator of
      transcription (STAT) pathway, well-activated by LPS in human macrophages as
      demonstrated by increased secretion of IFNbeta, STAT1 phosphorylation, and up
      regulation of reference IFNbeta-responsive genes, was concomitantly blocked by
      the JAK inhibitor. Most of cytokines targeted by ruxolitinib were shown to be
      regulated by IFNbeta in a JAK-sensitive manner. In addition, counteracting the
      IFNbeta/JAK/STAT cascade using a blocking monoclonal antibody directed against
      IFNbeta receptor resulted in a similar profile of cytokine repression to that
      observed in response to the JAK inhibitor. Overall, these data provide evidence
      for ruxolitinib-mediated repression of inflammatory cytokines in human
      macrophages through inhibition of the LPS/IFNbeta/JAK/STAT signalling pathway,
      which probably contributes to the anti-inflammatory effects of the JAK inhibitor.

PMID- 29202300
TI  - Dihydrofisetin exerts its anti-inflammatory effects associated with suppressing
      ERK/p38 MAPK and Heme Oxygenase-1 activation in lipopolysaccharide-stimulated RAW
      264.7 macrophages and carrageenan-induced mice paw edema.
AB  - Dihydrofisetin is a flavanonol derived from some edible wild herbs and
      traditional Chinese medicines. It has been found to possess many biological
      activities. However, the anti-inflammatory potential of Dihydrofisetin remains
      uncharacterized. The aim of the present study was to investigate the anti
      inflammatory activity of Dihydrofisetin and its underlying mechanisms. We found
      that Dihydrofisetin dose-dependently inhibited lipopolysaccharide-induced
      productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7
      macrophages, probably through suppressing the protein expressions of inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The expressions of pro
      inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and monocyte chemotactic
      protein (MCP-1) were also suppressed. We further demonstrated that Dihydrofisetin
      inhibited the activation of mitogen-activated protein kinases (MAPKs) pathway and
      phosphorylation of IkappaB-alpha whereas upregulated the expression of heme
      oxygenase-1 (HO-1). The in vivo carrageenan-induced mice paw edema study also
      indicated that treatment with 100 mg/kg of Dihydrofisetin could significantly
      inhibit carrageenan induced paw edema, decrease the levels of TNF-alpha, IL-6 and
      MDA, and increase the activity of GSH-Px in paw tissues. Taken together,
      Dihydrofisetin may act as a natural agent for treating inflammatory diseases by
      targeting MAPK, NF-kappaB and HO-1 pathways.

PMID- 29202301
TI  - Spleen tyrosine kinase inhibition ameliorates airway inflammation through
      modulation of NLRP3 inflammosome and Th17/Treg axis.
AB  - Repeated exposure to the fungal pathogen Aspergillus fumigates triggers spleen
      tyrosine kinase (SYK) signalling through dectin-1 activation, which is associated
      with deleterious airway inflammation. beta-Glucan-induced dectin-1 signalling
      activates the NLRP3 inflammasome, which in turn rapidly produces IL-1beta, a
      master regulator of inflammation. IL-1beta expression results in Th17/Treg
      imbalance, pulmonary inflammation, and bystander tissue injury. This study
      reports that 3,4 methylenedioxy-beta-nitrostyrene (MNS), a potent SYK inhibitor,
      markedly decreased the expression of pro-inflammatory cytokines and increased the
      expression of anti-inflammatory cytokines in vitro. Furthermore, SYK inhibition
      markedly decreased beta-glucan-induced IL-1beta expression, suggesting that SYK
      is indispensable for NLRP3 inflammasome activation. Decreased IL-1beta expression
      correlated with reduced Th17 response and enhanced immunosuppressive Treg
      response. Notably, SYK inhibition ameliorated inflammation caused by repeated
      intranasal beta-glucan challenge in BALB/C mice. SYK inhibition also restored the
      Th17/Treg balance via decreased Th17 and increased Treg responses, as evidenced
      by decreased IL-17 and ror-gamma levels. Additionally, inhibition of SYK
      increased IL-10 secreting CD4+FOXP3+ T cells that accompanied reduced T cell
      proliferation. Decreased IgA in the Bronchoalveolar lavage (BAL) fluid and serum
      also indicated the immunosuppressive potential of SYK inhibition. Histopathology
      data revealed that repeated beta-glucan challenge caused substantial pulmonary
      damage, as indicated by septal thickening and interstitial lymphocytic,
      neutrophil and granulocyte recruitment. These processes were effectively
      prevented by SYK inhibition, resulting in lung protection. Collectively, our
      findings suggest that SYK inhibition ameliorates dectin-1- mediated detrimental
      pulmonary inflammation and subsequent tissue damage. Therefore, SYK can be a new
      target gene in the therapeutic approach against fungal induced airway
      inflammation.

PMID- 29202302
TI  - Tin chemical shift anisotropy in tin dioxide: On ambiguity of CSA asymmetry
      derived from MAS spectra.
AB  - Two different axial symmetries of the 119Sn chemical shift anisotropy (CSA) in
      tin dioxide with the asymmetry parameter (eta) of 0 and 0.27 were reported
      previously based on the analysis of MAS NMR spectra. By analyzing the static
      powder pattern, we show that the 119Sn CSA is axially symmetric. A nearly axial
      symmetry and the principal axis system of the 119Sn chemical shift tensor in SnO2
      were deduced from periodic scalar-relativistic density functional theory (DFT)
      calculations of NMR parameters. The implications of fast small-angle motions on
      CSA parameters were also considered, which could potentially lead to a CSA
      symmetry in disagreement with a crystal symmetry. Our analysis of experimental
      spectra using spectral simulations and iterative fittings showed that MAS spectra
      recorded at relatively high frequencies do not show sufficiently distinct
      features in order to distinguish CSAs with eta ~ 0 and eta ~ 0.4. The example of
      SnO2 shows that both the MAS lineshape and spinning sideband analyses may
      overestimate the eta value by as much as ~0.3 and ~0.4, respectively. The results
      confirm that a static powder pattern must be analysed in order to improve the
      accuracy of the CSA asymmetry measurements. The measurements on SnO2
      nanoparticles showed that the asymmetry parameter of the 119Sn CSA increases for
      nm-sized particles with a larger surface area compared to MUm-sized particles.
      The increase of the eta value for tin atoms near the surface in SnO2 was also
      confirmed by DFT calculations.

PMID- 29202303
TI  - SPR imaging biosensor for the quantitation of fibronectin concentration in blood
      samples.
AB  - The purpose of this study was presentation of a new biosensor capable of
      determination of fibronectin. This biosensor was based on the specific
      interaction of anti-fibronectin antibody produced in rabbit with fibronectin. The
      surface plasmon resonance imaging (SPRI) technique was used as a detecting
      method. Optimization and characterization properties of the biosensor were
      studied. The determination of fibronectin concentration in natural samples was
      done. The results were compared with a reference method (Enzyme-Linked
      Immunosorbent Assay-ELISA). The analytically useful dynamic response range of
      biosensor is between 5 and 400ngmL-1. The detection limit is 1.5ngmL-1 and limit
      quantification is 5ngmL-1. The proposed SPRI biosensor showed good selectivity
      for potential interferences. It was applied to determine fibronectin
      concentrations in plasma of healthy donors and of patients after thermal injury.
      Good correlations between results obtained using the SPRI biosensor and ELISA
      test (correlation coefficients for healthy donors 0.996, for patients 0.984) were
      obtained. The average fibronectin concentration of healthy donors was 140.5+/
      24.6MUgmL -1 and the average fibronectin concentration of patients was 601.5+/
      72.1MUgmL -1, which was in agreement with results obtained by other
      investigators. The obtained results indicate that the developed biosensor may be
      a candidate for monitoring fibronectin concentration in blood samples.

PMID- 29202304
TI  - Development and validation of an UHPLC-MS/MS method for beta2-agonists
      quantification in human urine and application to clinical samples.
AB  - A fast analytical method for the simultaneous detection of 24 beta2-agonists in
      human urine was developed and validated. The method covers the therapeutic drugs
      most commonly administered, but also potentially abused beta2-agonists. The
      procedure is based on enzymatic deconjugation with beta-glucuronidase followed by
      SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic
      properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak
      resolution and rapid chromatographic separation, with reduced time and costs. The
      method was fully validated according ISO 17025:2005 principles. The following
      parameters were determined for each analyte: specificity, selectivity, linearity,
      limit of detection, limit of quantification, precision, accuracy, matrix effect,
      recovery and carry-over. The method was tested on real samples obtained from
      patients subjected to clinical treatment under chronic or acute therapy with
      either formoterol, indacaterol, salbutamol, or salmeterol. The drugs were
      administered using pressurized metered dose inhalers. All beta2-agonists
      administered to the patients were detected in the real samples. The method proved
      adequate to accurately measure the concentration of these analytes in the real
      samples. The observed analytical data are discussed with reference to the
      administered dose and the duration of the therapy.

PMID- 29202305
TI  - Development of a simple and sensitive liquid chromatography triple quadrupole
      mass spectrometry (LC-MS/MS) method for the determination of cannabidiol (CBD),
      Delta9-tetrahydrocannabinol (THC) and its metabolites in rat whole blood after
      oral administration of a single high dose of CBD.
AB  - The investigation of the possible conversion of cannabidiol (CBD) into Delta9
      tetrahydrocannabinol (THC) in vivo after oral administration of CBD is reported
      herein since recent publications suggested a rapid conversion in simulated
      gastric fluid. To this end, single high dose of CBD (50mg/kg) was administered
      orally to rats and their blood was collected after 3 and 6h. A highly sensitive
      and selective LC-MS/MS method was developed and fully validated in compliance
      with the Scientific Working Group of Forensic Toxicology (SWGTOX) standard
      practices for method validation in forensic toxicology. This method also involved
      the optimization of cannabinoids and their metabolites extraction in order to
      remove co-eluting phospholipids and increase the sensitivity of the MS detection.
      Neither THC nor its metabolites were detected in rat whole blood after 3 or 6h
      from CBD administration. After oral administration, the amount of CBD dissolved
      in olive oil was higher than that absorbed from an ethanolic solution. This could
      be explained by the protection of lipid excipients towards CBD from acidic
      gastric juice.

PMID- 29202306
TI  - Identification of cytotoxic metabolites from Mahonia aquifolium using 1H NMR
      based metabolomics approach.
AB  - Herein, we propose a 1H NMR-based metabolomics method to reveal cytotoxic
      metabolites from Mahonia aquifolium stem-bark. Primary and secondary metabolites
      in the Mahonia aquifolium extracts were identified by thorough analysis of 1H and
      2D NMR spectra, without prior isolation. An OPLS multivariate analysis method was
      used to correlate the chemical composition of the plant extracts with the results
      of cytotoxic activity against Human cervical adenocarcinoma cell line.
      Protoberberine alkaloids berberine and palmatine, along with
      bisbenzylisoquinoline alkaloid berbamine were identified as the most influential
      in the OPLS model, with the highest cytotoxic activity.

PMID- 29202307
TI  - The impact of free healthcare on women's capability: A qualitative study in rural
      Burkina Faso.
AB  - In March 2006, the government of Burkina Faso implemented an 80% subsidy for
      emergency obstetric and neonatal care (EmONC). To complement this subsidy, an NGO
      decided to cover the remaining 20% in two districts of the country, making EmONC
      completely free for women there. In addition, the NGO instituted fee exemptions
      for children under five years of age in those two districts. We conducted a
      qualitative study in 2011 to examine the impact of these free healthcare
      interventions on women's capability. We conducted semi-structured interviews with
      40 women, 16 members of health centre management committees, and eight healthcare
      workers in three health districts, as well as a documentary analysis. Results
      showed free healthcare helped reinforce women's capability to make health
      decisions by eliminating the need for them to negotiate access to household
      resources, which in turn helped shorten delays in health services use. Other
      effects were also observed, such as increased self-esteem among the women and
      greater respect within their marital relationship. However, cultural barriers
      remained, limiting women's capability to achieve certain things they valued, such
      as contraception. In conclusion, this study's results illustrate the
      transformative effect that eliminating fees for obstetric care can have on
      women's capability to make health decisions and their social position.
      Furthermore, if women's capability is to be strengthened, the results impel us to
      go beyond health and to organize social and economic policies to reinforce their
      positions in other spheres of social life.

PMID- 29202308
TI  - Morphology, cell-division, and phylogeny of Schmidingerothrix elongata spec. nov.
      (Ciliophora, Hypotricha), and brief guide to hypotrichs with Gonostomum-like oral
      apparatus.
AB  - The hypotrich Schmidingerothrix elongata spec. nov., discovered in saline
      (200/00) soil of the Longfeng Wetland, Daqing, northern China, was studied using
      live observation and protargol impregnation. It is characterized, inter alia, by
      colorless cortical granules arranged in short rows, three frontoventral cirral
      rows with the rightmost extending far posteriorly, and 4-8, usually six
      macronuclear nodules. Cell division proceeds as in congeners and confirms the
      lack of dorsal ciliature. In phylogenetic analyses based on SSU rDNA, S. elongata
      is sister of S. salinarum+Paracladotricha salina. A re-investigation of the type
      slides of P. salina, type of Paracladotricha, revealed a misobservation in the
      original description. Since P. salina lacks, like Schmidingerothrix spp., a
      dorsal ciliature, Paracladotricha becomes a junior, subjective synonym of
      Schmidingerothrix with S. salina comb. nov. as fourth species. A review of the
      phylogenetic analyses dealing with Schmidingerothrix shows that its position is
      variable. However, together with the gonostomatid oral apparatus it can be
      hypothesized that Schmidingerothrix is a member of the Gonostomatidae or a close
      relative. A list of genera (14) and species (58) which have - like
      Schmidingerothrix - a gonostomatid oral apparatus, as well as a key to these
      genera are provided.

PMID- 29202309
TI  - Thioautotrophic ectosymbiosis in Pseudovorticella sp., a peritrich ciliate
      species colonizing wood falls in marine mangrove.
AB  - Ciliates represent a diversified group of protists known to establish symbioses
      with prokaryotic micro-organisms. They are mainly phagotrophs and symbiotic
      relationships with bacteria can give them an important advantage in
      chemosynthetic environments. The aim of this study is to describe the thiotrophic
      association that occurs between the peritrich ciliate Pseudovorticella sp. and
      potential sulfur-oxidizing bacteria. Investigations at microscopic scale (LM,
      SEM, TEM) showed ectosymbiotic bacteria covering the surface of the body of
      Pseudovorticella sp. According to 16S rDNA phylogenetic analysis, these
      ectosymbiotic bacteria belong to gamma-proteobacteria and are phylogenetically
      close to the symbiont of the recently described Zoothamnium ignavum, which
      inhabits shallow-water wood falls. FISH experiments, using symbiont specific
      probes, clearly indicate that these ectosymbiotic bacteria are also ingested into
      food vacuoles. Electron lucent granules observed in TEM in the cytoplasm of the
      ectosymbiotic bacteria have been identified as sulfur granules by Raman
      microspectrometry analyses. Raman microspectrometry analyses confirmed the
      thiotrophic nature of this relationship already suggested by the results obtained
      by TEM and phylogeny. A complete sulfur map was then performed to investigate the
      sulfur distribution in the zooid. Results show that the relationship between this
      protist and its bacterial partner is a thiotrophic ectosymbiosis.

PMID- 29202310
TI  - Variation inflation factor-based regression modeling of anthropometric measures
      and temporal-spatial performance: Modeling approach and implications for clinical
      utility.
AB  - BACKGROUND: Understanding the relationship of underlying anthropometry to
      temporal-spatial performance is critical to appropriate assessment of patients
      with ambulatory dysfunction. The current body of literature has established the
      importance of limb length in this relationship. This study sought to re-examine
      these relationships in light of recent trends in body habitus and obesity, using
      Variation Inflation Factor analysis to optimize the model. METHODS: Elementary
      school children (n=452; ages 5-13) were tested during walking at a self-selected
      speed across an instrumented walkway. Temporal-spatial and anthropometric
      measures were compiled for all children. The relationship between temporal
      spatial and anthropometric measures was assessed using regression modeling with
      Variation Inflation Factor optimization. FINDINGS: Body weight was identified as
      a significant predictor of cycle duration, stride length, stance duration, and
      step width during initial modeling. However, it did not meet the constraints
      imposed during Variation Inflation Factor optimization and was removed from the
      final models. The final optimized models identified significant relationships
      between both temporal-spatial parameters of interest and other temporal-spatial
      measures, with the best fit identified for walking speed (R2=0.6148).
      INTERPRETATION: The use of the Variation Inflation Factor constraint during the
      regression modeling process ensured final models composed of truly independent
      predictor variables. The resulting models are highly robust and highlight the
      complex relationships between body structure, functional conditions, and walking
      performance. These models have value for routine clinical assessment of
      ambulatory dysfunction, and may provide a foundation for classifying temporal
      spatial performance in the context of multiple contributing parameters.

PMID- 29202311
TI  - Quantitative sensory response of the SCM muscle on sustained low level activation
      simulating co-contractions during bruxing.
AB  - OBJECTIVE: Bruxism is discussed as an etiological factor in the pathogenesis of
      orofacial and cervical pain. As the sternocleidomastoid muscle (SCM) is co
      activated during clenching, our aim was to investigate, whether the muscle
      loading leads to peripheral or central sensitizations. DESIGN: In twenty-one
      healthy female volunteers, somatosensory profiles of the SCM were recorded
      according to the test battery of the German Research Network on Neuropathic Pain
      (DFNS) prior to and after an isometric muscle exercise. QST comprised thermal and
      mechanical stimuli. A submaximal activation of the SCM (15% MVC) was kept for
      10min in sitting position. In separate test sessions one month apart, one sham
      and one verum experiment were conducted in randomized order. During the muscle
      loading, the parameters cold detection threshold (CDT), mechanical pain
      sensitivity (MPS) and pressure pain treshold (PPT) were tested and experimental
      pain recorded by visual analogoue scales (VAS). All test sessions were performed
      during the follicular phase of the menstrual cycle (day 5), to avoid effects on
      pain perception. Data were analyzed with Repeated Measures ANOVA (SPSS 22.0)
      RESULTS: No significant changes were found during or after (sham) loading except
      for stimulus-response-function (SR, P=0.01) and PPT (P=0.02) in the sham test. No
      effect was observed in the verum experiment (P=0.12 up to 1.0). CONCLUSION:
      Prolonged low level contraction of the SCM does not evoke painful sensitization.
      In contrast, submaximal muscle activation seems to have a protective effect
      corresponding to a training effect preventing sensitization.

PMID- 29202312
TI  - Bernstein's levels of movement construction: A contemporary perspective.
AB  - Explanation of how goal-directed movements are made manifest is the ultimate aim
      of the field classically referred to as "motor control". Essential to the sought
      after explanation is comprehension of the supporting functional architecture.
      Seven decades ago, the Russian physiologist and movement scientist Nikolai A.
      Bernstein proposed a hierarchical model to explain the construction of movements.
      In his model, the levels of the hierarchy share a common language (i.e., they are
      commensurate) and perform complementing functions to bring about dexterous
      movements. The science of the control and coordination of movement in the phylum
      Craniata has made considerable progress in the intervening seven decades. The
      contemporary body of knowledge about each of Bernstein's hypothesized functional
      levels is both more detailed and more sophisticated. A natural consequence of
      this progress, however, is the relatively independent theoretical development of
      a given level from the other levels. In this essay, we revisit each level of
      Bernstein's hierarchy from the joint perspectives of (a) the ecological approach
      to perception-action and (b) dynamical systems theory. We review a substantial
      and relevant body of literature produced in different areas of study that are
      accommodated by this ecological-dynamical version of Bernstein's levels.
      Implications for the control and coordination of movement and the challenges to
      producing a unified theory are discussed.

PMID- 29202313
TI  - Comparing interprofessional and interorganizational collaboration in healthcare:
      A systematic review of the qualitative research.
AB  - BACKGROUND: Interprofessional and interorganizational collaboration have become
      important components of a well-functioning healthcare system, all the more so
      given limited financial resources, aging populations, and comorbid chronic
      diseases. The nursing role in working alongside other healthcare professionals is
      critical. By their leadership, nurses can create a culture that encourages values
      and role models that favour collaborative work within a team context. OBJECTIVES:
      To clarify the specific features of conceptual frameworks of interprofessional
      and interorganizational collaboration in the healthcare field. This review,
      accordingly, offers insights into the key challenges facing policymakers,
      managers, healthcare professionals, and nurse leaders in planning, implementing,
      or evaluating interprofessional collaboration. DESIGN: This systematic review of
      qualitative research is based on the Joanna Briggs Institute's methodology for
      conducting synthesis. DATA SOURCES: Cochrane, JBI, CINAHL, Embase, Medline,
      Scopus, Academic Search Premier, Sociological Abstract, PsycInfo, and ProQuest
      were searched, using terms such as professionals, organizations, collaboration,
      and frameworks. METHODS: Qualitative studies of all research design types
      describing a conceptual framework of interprofessional or interorganizational
      collaboration in the healthcare field were included. They had to be written in
      French or English and published in the ten years between 2004 and 2014. RESULTS:
      Sixteen qualitative articles were included in the synthesis. Several concepts
      were found to be common to interprofessional and interorganizational
      collaboration, such as communication, trust, respect, mutual acquaintanceship,
      power, patient-centredness, task characteristics, and environment. Other concepts
      are of particular importance either to interorganizational collaboration, such as
      the need for formalization and the need for professional role clarification, or
      to interprofessional collaboration, such as the role of individuals and team
      identity. Promoting interorganizational collaboration was found to face greater
      challenges, such as achieving a sense of belonging among professionals when
      differences exist between corporate cultures, geographical distance, the
      multitude of processes, and formal paths of communication. CONCLUSIONS: This
      review sets a direction to follow for implementing changes that meet the
      challenge of a changing healthcare system and the transition towards non
      institutional care. It also shows that collaboration between nurses and
      healthcare professionals from different healthcare organizations is still poorly
      explored. This is a major limitation in the existing scientific literature,
      especially given the potential role that could be played by nurses in enhancing
      interorganizational collaboration.

PMID- 29202314
TI  - Serial evaluation of serum total reduction power potential by cyclic voltammetry
      in 30 dogs with gastric dilatation and volvulus- a randomised, controlled
      (lidocaine vs placebo), clinical trial.

PMID- 29202315
TI  - Effect of enrofloxacin and roxarsone on CYP450s in pig.
AB  - Enrofloxacin (ENR) and roxarsone (ROX) have been widely used in animal breeding.
      In this study, the daily clinical dosage of ENR and daily additive amount of ROX
      were administrated to Bama pigs. After 5days, the activity and protein expression
      of three important enzymes in the cytochrome P450 family were measured in the
      porcine liver. CYP1A2 was induced by both ENR and ROX independently. CYP2E1 and
      CYP3A4 were inhibited by ENR, but not affected by ROX. The combined
      administration of ENR and ROX were antagonistic to CYP1A2 and CYP2E1, but not to
      CYP3A4. Drug-drug interactions should be considered during the administration of
      ENR, ROX and for their co-administration with other drugs to minimize adverse
      reactions.

PMID- 29202316
TI  - Drug law reform, performativity and the politics of childhood.
AB  - Children are critical to debates about drug law reform. For both advocates of
      liberalisation and, especially, defenders of prohibition, the protection of
      children is an important rhetorical device in pressing for, or resisting, change.
      However, the privileged position of minors within such discussions, or talk about
      drugs in general, has rarely been explored in any depth in either drug and
      alcohol studies or legal research. Drawing on scholarship on performativity, and
      particularly John Law's work on 'collateral realities', this article will
      consider how constructs such as childhood and drugs are 'produced' and '(re)made'
      in such discourses. Through analysis of legal measures, policy
      documents/statements submitted to the UN General Assembly Special Session on
      Drugs (UNGASS) in 2016, and scientific discussion, it will be argued that such
      'realities' include the constitution of the child as the logical victim of drugs
      (and the natural beneficiary or casualty of reform), and the enactment of drugs
      as an inherent threat to children. It is suggested that drug policy research
      needs to pay attention to age as a social construct and cultural category, and
      that a critical awareness of the relevance of age in policy discourse is as
      necessary as, for example, race, class or gender. Moreover, attendance to the
      ontological politics of constructs such as 'childhood' and 'drugs' is important
      if law and policy measures are to account for young people's agency.

PMID- 29202317
TI  - Women victims of intentional homicide in Italy: New insights comparing Italian
      trends to German and U.S. trends, 2008-2014.
AB  - National statistics on female homicide could be a useful tool to evaluate the
      phenomenon and plan adequate strategies to prevent and reduce this crime. The aim
      of the study is to contribute to the analysis of intentional female homicides in
      Italy by comparing Italian trends to German and United States trends from 2008 to
      2014. This is a population study based on data deriving primarily from national
      and European statistical institutes, from the U.S. Federal Bureau of
      Investigation's Uniform Crime Reporting and from the National Center for Health
      Statistics. Data were analyzed in relation to trends and age by Chi-square test,
      Student's t-test and linear regression. Results show that female homicides,
      unlike male homicides, remained stable in the three countries. Regression
      analysis showed a higher risk for female homicide in all age groups in the U.S.
      Middle-aged women result at higher risk, and the majority of murdered women are
      killed by people they know. These results confirm previous findings and suggest
      the need to focus also in Italy on preventive strategies to reduce those
      precipitating factors linked to violence and present in the course of a
      relationship or within the family.

PMID- 29202318
TI  - Single session tDCS over the left DLPFC disrupts interference processing.
AB  - Whether single session tDCS can impact upon cognition in healthy subjects is
      currently a heated debate against the background of inconsistent results. In view
      of the current methodological discussion concerning tDCS we developed an
      alternative approach to measure effects of single session tDCS on the Stroop
      task. The left DLPFC was stimulated in a pre-post design using a new electrode
      set-up (a 9 cm2 electrode was placed over the left DLPFC while a 35 cm2 was
      placed over the parieto-occipital cortex) contrasting anodal versus cathodal
      stimulation. The Stroop task was optimized concerning confounding variables that
      were not controlled in previous attempts to measure the effects of single-session
      tDCS on the Stroop task. In our sample of N = 32 healthy students we observed a
      significant single session tDCS effect on the Stroop effect in the error data as
      in our study cathodal stimulation as compared to anodal stimulation of the left
      DLPFC disrupted interference processing. This result confirms previous studies
      suggesting that neuromodulation of the left DLPFC impacts interference
      processing. Single-session tDCS can impact upon cognitive processes. A rigorous
      methodical approach is emphasized as the effects seem to be only of small to
      medium size.

PMID- 29202319
TI  - Dimeric sesquiterpenoid-4H-chromone derivatives from agarwood of Aquilaria
      crassna and their cytotoxicity.
AB  - Six previously undescribed uncommon ester-bonded dimeric compounds
      (aquilacrassnins A-F) containing a sesquiterpenoid and a 5,6,7,8-tetrahydroxy-2
      (2-phenylethyl)-5,6,7,8-tetrahydro -4H-chromone units were isolated from the
      EtOAc extract of agarwood originating from Aquilaria crassna. Their structures
      were elucidated by spectroscopic (NMR, UV, IR, MS, and ECD) methods. All the
      compounds were tested for AChE inhibitory activity and cytotoxicity against K562,
      BEL-7402, SGC-7901, Hela, and A549 tumor cell lines. The results showed that
      aquilacrassnin A, B, and E exhibited weak cytotoxicity against the five tested
      cell lines, whereas all the compounds were inactive against AChE.

PMID- 29202320
TI  - Screening itself for disseminated intravascular coagulation may reduce mortality
      in sepsis: A nationwide multicenter registry in Japan.
AB  - OBJECTIVES: Screening of patients with sepsis for disseminated intravascular
      coagulation (DIC) has been recommended in several guidelines. However, DIC
      screening is still not widely accepted as an essential component of sepsis
      management, partly because of a lack of evidence that DIC screening has an effect
      on mortality. We investigated whether DIC screening was associated with a
      survival benefit in patients with sepsis. DESIGN: Post hoc analysis of a
      nationwide multicenter retrospective cohort study. SETTING: 42 intensive care
      units in Japan. PARTICIPANTS: 2663 adult patients diagnosed as having severe
      sepsis: 1893 (71.1%) patients were considered candidates for and 770 (28.9%)
      patients were not considered candidates for International Society of Thrombosis
      and Hemostasis (ISTH) overt DIC screening on ICU day 1. MAIN OUTCOME MEASURES:
      The primary outcome measure was all-cause in-hospital mortality. Patients were
      stratified according to whether DIC screening was performed at the time of ICU
      admission (day 1) to investigate the survival effect associated with DIC
      screening. We also evaluated survival benefit by classifying patients according
      to whether DIC screening was performed on day 1 and repeated on day 3. Effects of
      screening on mortality were assessed using Cox proportional hazards models
      adjusted by the inverse probability of treatment weighting (IPTW) method using
      propensity scoring. RESULTS: After adjustment for imbalances, ISTH overt DIC
      screening on day 1 was associated with significantly lower mortality (IPTW
      adjusted HR: 0.836; 95% confidence interval [CI]: 0.711-0.984), and this
      association became even stronger when ISTH overt DIC screening was repeated on
      day 3 (IPTW-adjusted HR: 0.727; 95% CI: 0.597-0.884). Besides, we observed an
      almost comparable effect on mortality associated with DIC screening using the
      Japanese Association for Acute Medicine criteria. CONCLUSION: DIC screening was
      associated with a reduction in mortality in patients with sepsis. This
      association could be even stronger by repeating DIC screening.

PMID- 29202321
TI  - Quantitative analysis of breast cancer diagnosis using a probabilistic modelling
      approach.
AB  - BACKGROUND: Breast cancer is the most prevalent cancer in women in most countries
      of the world. Many computer-aided diagnostic methods have been proposed, but
      there are few studies on quantitative discovery of probabilistic dependencies
      among breast cancer data features and identification of the contribution of each
      feature to breast cancer diagnosis. METHODS: This study aims to fill this void by
      utilizing a Bayesian network (BN) modelling approach. A K2 learning algorithm and
      statistical computation methods are used to construct BN structure and assess the
      obtained BN model. The data used in this study were collected from a clinical
      ultrasound dataset derived from a Chinese local hospital and a fine-needle
      aspiration cytology (FNAC) dataset from UCI machine learning repository. RESULTS:
      Our study suggested that, in terms of ultrasound data, cell shape is the most
      significant feature for breast cancer diagnosis, and the resistance index
      presents a strong probabilistic dependency on blood signals. With respect to FNAC
      data, bare nuclei are the most important discriminating feature of malignant and
      benign breast tumours, and uniformity of both cell size and cell shape are
      tightly interdependent. CONTRIBUTIONS: The BN modelling approach can support
      clinicians in making diagnostic decisions based on the significant features
      identified by the model, especially when some other features are missing for
      specific patients. The approach is also applicable to other healthcare data
      analytics and data modelling for disease diagnosis.

PMID- 29202322
TI  - Accident frequency and unrealistic optimism: Children's assessment of risk.
AB  - Accidental injury is a major cause of mortality and morbidity among children,
      warranting research on their risk perceptions. Three hundred and seven children
      aged 10-11 years assessed the frequency, danger and personal risk likelihood of 8
      accidents. Two social-cognitive biases were manifested. The frequency of rare
      accidents (e.g. drowning) was overestimated, and the frequency of common
      accidents (e.g. bike accidents) underestimated; and the majority of children
      showed unrealistic optimism tending to see themselves as less likely to suffer
      these accidents in comparison to their peers, offering superior skills or
      parental control of the environment as an explanation. In the case of pedestrian
      accidents, children recognised their seriousness, underestimated the frequency of
      this risk and regarded their own road crossing skill as protection. These
      findings highlight the challenging task facing safety educators who, when
      teaching conventional safety knowledge and routines, also need to alert children
      to the danger of over-confidence without disabling them though fear.

PMID- 29202323
TI  - Identifying traffic accident black spots with Poisson-Tweedie models.
AB  - This paper aims at the identification of black spots for traffic accidents, i.e.
      locations with accident counts beyond what is usual for similar locations, using
      spatially and temporally aggregated hospital records from Funen, Denmark.
      Specifically, we apply an autoregressive Poisson-Tweedie model, which covers a
      wide range of discrete distributions and handles zero-inflation as well as
      overdispersion. The estimated power parameter of the model was 1.6 (SE=0.06)
      suggesting a distribution close to the Polya-Aeppli distribution. We identified
      nine black spots consistently standing out in all six considered calendar years
      and calculated by simulations a probability of p=0.03 for these to be chance
      findings. Altogether, our results recommend these sites for further investigation
      and suggest that our simple approach could play a role in future area based
      traffic accident prevention planning.

PMID- 29202324
TI  - Sex differences evident in self-reported but not objective measures of driving.
AB  - It has been consistently reported that women self-regulate their driving more
      than men. Volunteer drivers aged 75 years and older from the suburban outskirts
      of Sydney, Australia joined a longitudinal study in 2012-2014. GPS in-vehicle
      monitoring was used to objectively measure driving and surveys of driving
      patterns. The study included 343 drivers (203/343, 59% men) with an average age
      of 80 years. Our results revealed that men were 3.85 times more likely to report
      driving beyond their local shire during the past year (95% CI 2.03-5.72) and 1.81
      times more likely to report that they do not avoid night driving (95% CI 1.21
      3.22). In contrast sex was not predictive of any objective measure of driving
      during a one-week period of monitoring. These findings suggest that men and women
      report different self-regulation practices but that actual driving exposure is
      quite similar. These findings can inform strategies to promote safe mobility.

PMID- 29202326
TI  - Substitution of Fried's performance-based physical frailty criteria with self
      report questions.
AB  - OBJECTIVE: To identify self-report questions that can substitute Fried's
      performance-based frailty measures for use in large-scale studies and daily
      practice. METHODS: A cross-sectional study was conducted among community dwelling
      older people (65+). Based on a literature search and interviews with older people
      and experts, 11 questions concerning walk time and 10 on handgrip strength were
      selected. All participants completed these sets of self-report questions as well
      as the original Fried criteria (including performance-based tests). Regression
      analyses were performed to find the questions that best substituted the
      performance-based tests. RESULTS: In total, 135 individuals (mean age 73.8+/-7.0,
      58.5% female) in different stages of frailty (non-frail 38.5%, pre-frail 40.7%,
      frail 20.7%) were included. Regression analyses revealed four questions for walk
      time and two for handgrip strength. Cut-off values of three for walk time (range
      0-5) and one for handgrip strength (range 0-3) seem most optimal. This resulted
      in a sensitivity of 69.2%, 86.1% specificity and 79.4% agreement for walk time
      and a sensitivity of 73.2%, 71.3% specificity and 71.9% agreement for handgrip
      strength. The comparison of frailty stages using frailty criteria including the
      performance-based measures and scores based solely on self-report questions,
      resulted in an observed agreement of 71.1% (kappa value=0.55). CONCLUSIONS:
      Considering the agreement between the questions and the performance-based tests,
      these two sets of questions might be used in settings where the performance-based
      tests of walk time and handgrip strength are unfeasible, such as in daily
      practice and large-scale research.

PMID- 29202325
TI  - Co-delivery of human cancer-testis antigens with adjuvant in protein
      nanoparticles induces higher cell-mediated immune responses.
AB  - Nanoparticles have attracted considerable interest as cancer vaccine delivery
      vehicles for inducing sufficient CD8+ T cell-mediated immune responses to
      overcome the low immunogenicity of the tumor microenvironment. Our studies
      described here are the first to examine the effects of clinically-tested human
      cancer-testis (CT) peptide epitopes within a synthetic nanoparticle.
      Specifically, we focused on two significant clinical CT targets, the HLA-A2
      restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging
      strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope
      (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2
      nanoparticle), resulted in a 25-fold increase in specific IFN-gamma secretion in
      HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity
      toward target cancer cells expressing the antigen. Immunization with a MAGE-A3
      epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in
      specific IFN-gamma secretion and cell lysis by 6-fold and 9-fold, respectively.
      Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2
      nanoparticles yielded an additive effect that increased lytic activity towards
      cells bearing NY-ESO-1+ and MAGE-A3+. Our investigations demonstrate that
      formulation of CT antigens within a nanoparticle can significantly enhance
      antigen-specific cell-mediated responses, and the combination of the two antigens
      in a vaccine can preserve the increased individual responses that are observed
      for each antigen alone.

PMID- 29202328
TI  - DNA damage signaling and polyploid macrophages in chronic inflammation.
AB  - Whole genome duplications, an important step in cancer development, also occur in
      the macrophage lineage in disease: large multinucleated macrophages found within
      compact, ordered aggregates of immune cells, called granulomas, are a well-known
      histologic entity. Very recent work suggests that granuloma macrophages
      remarkably acquire epithelial cell features and the genotoxic stress response
      instructs granuloma macrophage genome duplications, suggesting that granuloma
      macrophages and pre-malignant epithelial cells may share common mechanisms of
      adaptation to chronic genotoxic stress. Exploring these mechanisms is key for a
      better understanding of the pathogenesis of chronic inflammatory diseases. Here
      we review the mechanisms of macrophage polyploidization, the role of DNA damage
      signaling in this process and the function of polyploid macrophages, with a focus
      on chronic inflammation.

PMID- 29202327
TI  - Mesh electronics: a new paradigm for tissue-like brain probes.
AB  - Existing implantable neurotechnologies for understanding the brain and treating
      neurological diseases have intrinsic properties that have limited their
      capability to achieve chronically-stable brain interfaces with single-neuron
      spatiotemporal resolution. These limitations reflect what has been dichotomy
      between the structure and mechanical properties of living brain tissue and non
      living neural probes. To bridge the gap between neural and electronic networks,
      we have introduced the new concept of mesh electronics probes designed with
      structural and mechanical properties such that the implant begins to 'look and
      behave' like neural tissue. Syringe-implanted mesh electronics have led to the
      realization of probes that are neuro-attractive and free of the chronic immune
      response, as well as capable of stable long-term mapping and modulation of brain
      activity at the single-neuron level. This review provides a historical overview
      of a 10-year development of mesh electronics by highlighting the tissue-like
      design, syringe-assisted delivery, seamless neural tissue integration, and single
      neuron level chronic recording stability of mesh electronics. We also offer
      insights on unique near-term opportunities and future directions for neuroscience
      and neurology that now are available or expected for mesh electronics
      neurotechnologies.

PMID- 29202329
TI  - Relationship of ROS accumulation and superoxide dismutase isozymes in developing
      anther with floret fertility of rice under heat stress.
AB  - High temperature (HT) at meiosis stage is one of most important environment
      constraint affecting spikelet fertility and rice yield. In this paper, the
      effects of HT exposure at meiosis stage on the ROS (reactive oxygen species)
      accumulation, various superoxide dismutase (SOD, EC1.15.1.11) isozymes in
      developing anther, and its relationship with HT-induced decline in pollen
      viability and floret fertility were investigated by using four rice cultivars
      differing in heat tolerance under well-controlled climatic condition. Results
      showed that HT exposure significantly increased ROS level and malondialdehyde
      (MDA) content in rice anther, and this occurrence was strongly responsible for
      the HT-induced decline in pollen viability and harmful effect of HT adversity on
      floret fertility. However, the increased extent of ROS concentration in rice
      anther under HT exposure was greatly variable, depending on both the intensity
      and duration of HT exposure and different rice cultivars used. The SOD and CAT
      activities of HT-sensitive cultivars decreased more profoundly than those of HT
      tolerant cultivars under the same HT regimes. Among various types of SOD enzymes,
      Cu/Zn-SODa expressed highly in rice anther and responded sensitively to HT
      exposure, while Cu/Zn-SODb expressed weakly in rice anther and preferentially in
      rice leaves. HT exposure suppressed the expression of Cu/Zn-SODa in developing
      anther, which was closely associated with the down-regulated transcripts of
      cCu/Zn-SOD1 gene. Hence, Cu/Zn-SODa may play a central role in the regulation of
      total SOD activity and ROS detoxification in rice anther as affected by HT
      exposure at meiosis stage.

PMID- 29202330
TI  - Genetic alterations in sporadic triple negative breast cancer.
AB  - BACKGROUND: Recent studies have aimed to identify gene mutation profiles to
      explain the cause of TNBC therapy limitations. METHODS: The purpose of our study
      was to use Next Generation Sequencing (NGS) of 46 genes with a well-defined role
      in cancer in a cohort of TNBC patients in order to identify novel markers that
      could lead to the development of strategic, adjuvant, gene-targeted therapies.
      RESULTS: A total of 118 gene mutations in 35 genes, 75 mutations in BRCA1 and 92
      mutations in BRCA2 were identified. The clinical assessment of the identified
      mutations showed 27 to be possibly damaging and 59 to be damaging. TP53, KDR,
      PIK3CA (rs3729687), ATM, AKT1 and KIT were among the most frequently mutated
      genes in our TNBC cohort. The SNP AKT1 (rs3730358) was suggested to modify the
      risk of breast cancer. SNP PIK3CA (rs3729687) is a damaging mutation that we
      found to be correlated with the prognosis of TNBC. The survival curve analysis
      showed that the presence of AKT1, TP53, KDR, KIT, BRCA1 and BRCA2 mutations is
      correlated with a poor prognosis. CONCLUSION: We show a strong association
      between TNBC and mutations in BRCA1/2 genes and the poor outcome of these
      patients. Moreover, we identified several other unknown mutations putatively
      associated with the poor prognosis of TNBC tumors. We also discovered novel
      mutations never before associated with breast cancer that could putatively
      account for the poor prognosis of the TNBC tumors.

PMID- 29202331
TI  - Using the ICF in transition research and practice? Lessons from a scoping review.
AB  - BACKGROUND: The International Classification of Functioning, Disability and
      Health (ICF) and subsequent ICF-CY (child and youth version) recognize the
      importance of personal and environmental factors in facilitating holistic
      transition planning and service delivery for youth with chronic health conditions
      (YCHC). AIMS: The objective of this scoping review is to investigate the degree
      to which the ICF and ICF-CY have been used in transition research and practice
      since its initial publication. METHODS: Arksey and O'Malley's five-stage
      methodological framework guided the scoping review using the following databases:
      AMED, CINAHL, EMBASE, HealthSTAR, MEDLINE, and PsycINFO. Keywords included:
      'ICF', 'ICF-CY', and 'transition', which were adapted to each database. RESULTS:
      25 articles met final inclusion. Two key themes emerged regarding use of the ICF:
      1) the ICF enhances transdisciplinary processes to inform transition planning and
      interventions; and 2) the ICF facilitates comprehensive and developmentally
      appropriate transition services over a youth's lifecourse. The strengths and
      limitations of the ICF in guiding the planning and delivery of transition
      services are discussed. Some limitations include the large number of items
      inherent within the ICF and a lack of clarity between the components of activity
      and participation. CONCLUSION: Key recommendations include: i) further
      explanation and development of items for quality of life and well-being, personal
      factors, and psychological issues; and ii) additional research to advance
      knowledge towards developing empirically- based evidence for the application of
      the ICF in clinical practice to facilitate transition.

PMID- 29202332
TI  - Chloro(triphenylphosphine)gold(I) a forefront reagent in gold chemistry as
      apoptotic agent for cancer cells.
AB  - The antiproliferative activity of the gold complex [Au(tpp)Cl] (1)
      (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and
      normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound
      exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic
      pathway, especially though the mitochondrion damage was concluded by cell cycle
      arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and
      Propidium Iodide (PI) as indicators, assays and permeabilization of the
      mitochondrial membrane tests. The molecular mechanism of action of 1 was further
      studied by: (i) its catalytic activity on the oxidation of linoleic acid (an acid
      that partakes in membrane fluidity) to hyperoxolinoleic acid by oxygen and (ii)
      its binding affinity towards the calf thymus (CT) DNA. Since the deactivation of
      cisplatin by glutathione (GSH), is related with the development of cell
      resistance, the reaction of 1 with GSH was investigated by UV absorption
      spectroscopy. The absence of micronucleus in cells confirms that the complex has
      no in vitro toxicity. The in vivo genotoxicity caused by 1 was evaluated by
      Allium cepa test.

PMID- 29202333
TI  - Aortic atherosclerosis is a key modulator of the prognostic value of postural
      blood pressure changes.
AB  - BACKGROUND AND AIMS: Orthostatic blood pressure decrease or increase has been
      related to cardiovascular events in hypertensive patients. Large blood pressure
      changes after orthostatic stress are associated with autonomic and neurohormonal
      abnormalities; aortic atherosclerosis (ATS) may also play a role. METHODS: We
      investigated the interaction of ATS on the prognostic value of postural blood
      pressure changes. In a cohort of 958 hypertensive patients with an aortography
      (mean +/- standard deviation age 44 +/- 11 years, 61% men, mean blood pressure
      182/110 mmHg), blood pressure was measured after 10 min of rest in the supine
      position. Systolic blood pressure (SBP) was also measured in standing position, 1
      min after the supine position. Blood pressure changes were calculated as supine
      SBP minus standing SBP and analyzed as absolute or arithmetic means. ATS was
      assessed using an aortography score. RESULTS: After 15 years of follow-up, 280
      all-cause and 167 cardiovascular deaths occurred. In a multivariable Cox
      regression analysis adjusted for major cardiovascular risk factors and stratified
      according to ATS status, SBP changes were statistically associated with all-cause
      and cardiovascular mortality only in the presence of ATS: tertile 3 versus 1,
      2.99 (1.37-6.49) and 4.08 (1.55-10.72) respectively, tertile 3 versus 2, 2.89
      (1.29-6.46) and 4.82 (1.79-12.98), respectively (p for interaction: 0.003 for all
      cause and 0.003 for cardiovascular mortality) for absolute changes. The hazard
      associated with the magnitude of SBP changes was more important than that
      associated with its direction. CONCLUSIONS: The prognostic significance of
      postural SBP changes is markedly influenced by ATS in hypertensive patients.

PMID- 29202334
TI  - Berberine treatment increases Akkermansia in the gut and improves high-fat diet
      induced atherosclerosis in Apoe-/- mice.
AB  - BACKGROUND AND AIMS: Gut microbiota plays a major role in metabolic disorders.
      Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism
      underlying the role of berberine in modulating metabolic disorders is not fully
      clear because berberine has poor oral bioavailability. Thus, we evaluated whether
      the antiatherosclerotic effect of berberine is related to alterations in gut
      microbial structure and if so, whether specific bacterial taxa contribute to the
      beneficial effects of berberine. METHODS: Apoe-/- mice were fed either a normal
      chow diet or a high-fat diet (HFD). Berberine was administered to mice in
      drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established
      by high throughput sequencing of the V3-V4 region of the bacterial 16S ribosomal
      RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation
      and gut barrier integrity were also investigated. RESULTS: Berberine treatment
      significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance
      was markedly increased in HFD-fed mice treated with berberine. Moreover,
      berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and
      intestinal expression of proinflammatory cytokines and chemokines. Berberine
      treatment increased intestinal expression of tight junction proteins and the
      thickness of the colonic mucus layer, which are related to restoration of gut
      barrier integrity in HFD-fed mice. CONCLUSIONS: Modulation of gut microbiota,
      specifically an increase in the abundance of Akkermansia, may contribute to the
      antiatherosclerotic and metabolic protective effects of berberine, which is
      poorly absorbed orally. Our findings therefore support the therapeutic value of
      gut microbiota manipulation in treating atherosclerosis.

PMID- 29202335
TI  - Sweet taste preference in binge-eating disorder: A preliminary investigation.
AB  - Research suggests that individuals with high liking for sweets are at increased
      risk for binge eating, which has been minimally investigated in individuals with
      binge-eating disorder (BED). Forty-one adults (85% female, 83% white) with binge
      eating concerns completed a sweet taste test and measures of eating disorder
      behaviors and food cravings. A subset of participants with BED completed an oral
      glucose tolerance test (OGTT; N=21) and a 24-hour dietary recall (N=26).
      Regression models were used to compare highest sweet preferers (HSP [N=18]) to
      other sweet preferers (OSP [N=23]) and were used to assess associations between
      sweet taste preference and outcome variables. Effect sizes (etap2) for
      differences between HSP and OSP ranged from small (<=0.01) to large (>=0.24);
      group differences were statistically nonsignificant except for 24-hour caloric
      intake (etap2=0.16, p=0.04), protein intake (etap2=0.16, p=0.04), and insulin
      sensitivity index (etap2=0.24, p=0.04), which were higher in HSP, and
      postprandial insulin, which was smaller in HSP (etap2=0.27, p=0.03). Continuous
      analyses replicated postprandial insulin response. Compared with OSP, HSP
      reported numerically higher binge-eating frequency (etap2=0.04), over-eating
      frequency (etap2=0.06), and carbohydrate intake (etap2=0.14), and they exhibited
      numerically smaller postprandial glucose AUC (etap2=0.16). Sweet taste preference
      may have implications for glucose regulation, binge-eating frequency, and
      nutrient intake in BED.

PMID- 29202337
TI  - Using handwriting to infer a writer's country of origin for forensic intelligence
      purposes.
AB  - Forensic science has traditionally focused the majority of its resources and
      objectives towards addressing Court-related questions. However, this view
      restricts the contribution of forensic science to one process and results in a
      loss of information as the investigative and intelligence roles are largely
      neglected. A forensic science discipline suffering from this imbalance is
      handwriting examination, which may be characterised as a time consuming and
      subjective process that is mostly carried out towards the end of the
      investigation for the purpose of judicial proceedings. Individual and habitual
      characteristics are the major handwriting features exploited, however alternate
      information concerning the author's native language could potentially be used as
      a key element in an intelligence framework. This research focussed on the
      detection of characteristics that differentiate Vietnamese and English Australian
      writers based on their English handwriting. The study began with the extraction
      of handwriting characteristics from the writing of people from the two
      populations. The data was analysed using a logistic regression model and a
      classification and regression tree (CRT). Each recognised four class
      characteristics that were capable of distinguishing between the two
      nationalities. The logistic regression and CRT models were both capable of
      correctly predicting 93% of cases. Their predictive capabilities were then tested
      and supported using blind exemplars in order to mirror casework settings. It
      appeared that when using their respective class characteristics, the two models
      were capable of differentiating English Australians from Vietnamese in the data
      set. This proof of concept research demonstrated the plausibility of exploiting
      this additional information from a handwriting trace and taking advantage of it
      in an intelligence-led framework.

PMID- 29202336
TI  - Colonization, localization, and inflammation: the roles of H. pylori chemotaxis
      in vivo.
AB  - Helicobacter pylori is a Gram-negative bacterium that infects half of the world's
      population, causing gastritis, peptic ulcers, and gastric cancer. To establish
      chronic stomach infection, H. pylori utilizes chemotaxis, driven by a conserved
      signal transduction system. Chemotaxis allows H. pylori to sense an array of
      environmental and bacterial signals within the stomach, guiding its motility
      towards its preferred niche within the gastric mucosa and glands. Fine-tuned
      localization, regulated by the chemotaxis system, enables robust colonization
      during the acute stage of infection. During chronic infection, chemotaxis helps
      maintain bacterial populations and modulates the host immune response. Given its
      importance in host colonization and disease, chemotaxis is an attractive target
      for future treatments against H. pylori infections.

PMID- 29202338
TI  - Cranial trauma in handgun executions: Experimental data using polyurethane
      proxies.
AB  - Gun violence is a global phenomenon with regional variation in frequency and
      severity. Handguns are often used in violent deaths such as suicides and
      homicides. Hence, ballistic trauma is a critical subject of forensic
      investigations. Trauma patterns are fundamental evidence for the reconstruction
      of the incident and for the determination of the manner of death. This study
      investigated the differences in trauma patterns with a series of experiments
      using six different calibers (.22 LR, .38 Special, .380 ACP, 9*19mm, .40 S&W, and
      .45 ACP) and four different bullet types. Synbone(r) spheres (polyurethane bone
      proxies) were used for close range 30cm simulated executions. The polyurethane
      spheres constitute an excellent proxy for human crania at the macroscopic level
      as suggested by other studies. The results showed that the radius of the entrance
      wound is positively correlated (Pearson's correlation coefficient R=0.846,
      p<0.05) with the caliber dimension. As muzzle velocity increased, endocranial
      beveling increased. Bullet weight, conversely, does not seem to have an effect on
      the size of the endocranial beveling present in Synbone(r) spheres. The ballistic
      experiments exhibited similarities in entrance wound morphology; radial and
      concentric fracture patterns, hydraulic burst effect, circumferential
      delamination, and endocranial beveling with that of documented forensic cases
      with corresponding caliber shot. Synbone spheres seem appropriate for ballistic
      simulations of cranial injuries; yet, more research is needed to verify these
      observations.

PMID- 29202339
TI  - Heat-denatured lysozyme could be a novel disinfectant for reducing hepatitis A
      virus and murine norovirus on berry fruit.
AB  - Hepatitis A virus (HAV) is well known worldwide as a causative virus of acute
      hepatitis. In recent years, numerous cases of HAV infection caused by HAV
      contaminated berries have occurred around the world. Because berries are often
      consumed without prior heating, reliable disinfection of the raw fruit is
      important in order to prevent HAV outbreaks. Previous studies have found that
      murine norovirus strain 1 (MNV-1) and human norovirus GII.4 were inactivated in
      heat-denatured lysozyme solution. In this study, we investigated whether or not
      heat-denatured lysozyme is effective in inactivating HAV and whether it could be
      an effective disinfectant for berries contaminated with HAV or MNV-1. We examined
      the inactivating effect of heat-denatured lysozyme on three strains of HAV and
      found that it reduced the infectivity of all three strains. We then immersed
      blueberries and mixed berries into solutions of HAV or MNV-1, and disinfected
      them by soaking them in 1% heat-denatured lysozyme for 1min. Consequently, the
      infectious HAV and MNV-1 contaminating the berries were decreased by >3.1 log
      units in all samples. Our results demonstrate that heat-denatured lysozyme
      effectively inactivates HAV and suggest that heat-denatured lysozyme may be an
      effective disinfectant for berry fruit, which is a potential source of HAV food
      poisoning.

PMID- 29202340
TI  - MALDI-TOF MS as a tool to identify foodborne yeasts and yeast-like fungi.
AB  - Since food spoilage by yeasts causes high economic losses, fast and accurate
      identifications of yeasts associated with food and food-related products are
      important for the food industry. In this study the efficiency of the matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) to identify food related yeasts was evaluated. A CBS in-house MALDI-TOF MS
      database was created and later challenged with a blinded test set of 146 yeast
      strains obtained from food and food related products. Ninety eight percent of the
      strains were correctly identified with log score values>1.7. One strain, Mrakia
      frigida, gained a correct identification with a score value<1.7. Two strains
      could not be identified at first as they represented a mix of two different
      species. These mixes were Rhodotorula babjevae with Meyerozyma caribbica and
      Clavispora lusitaniae with Debaryomyces hansenii. After separation, all four
      species could be correctly identified with scores>1.7. Ambiguous identifications
      were observed due to two incorrect reference mass spectra's found in the
      commercial database BDAL v.4.0, namely Candida sake DSM 70763 which was re
      identified as Candida oleophila, and Candida inconspicua DSM 70631 which was re
      identified as Pichia membranifaciens. MALDI-TOF MS can distinguish between most
      of the species, but for some species complexes, such as the Kazachstania telluris
      and Mrakia frigida complexes, MALDI-TOF MS showed limited resolution and
      identification of sibling species was sometimes problematic. Despite this, we
      showed that the MALDI-TOF MS is applicable for routine identification and
      validation of foodborne yeasts, but a further update of the commercial reference
      databases is needed.

PMID- 29202341
TI  - Bridging the structural gap of glycoproteomics with ion mobility spectrometry.
AB  - Over the past two decades mass spectrometry (MS) has enabled high throughput
      studies on the level of a complex proteome. While it has similarly advanced
      glycobiology, the level of progress has been more restrained. This is in large
      part due to the diversity and complexity of carbohydrate structures. While MS is
      now routinely used for glycobiology, it suffers from a critical limitation, that
      is the inability to resolve isobaric structures. Since so many structurally and
      functionally distinct carbohydrates are indistinguishable by MS, additional
      techniques are needed for detailed structural analysis. Ion mobility spectrometry
      (IMS), with its ability to resolve closely related isobaric structures, presents
      such a tool for alleviating the current limitations of MS. In the past few years
      studies have demonstrated the utility and immense potential of combining IMS with
      MS (IM-MS) for glycomics and it is now approaching the point of enabling
      comprehensive structural studies on the level of the glycoproteome.

PMID- 29202342
TI  - D-Tyrosine loaded nanocomposite membranes for environmental-friendly, long-term
      biofouling control.
AB  - Strategies to control biofouling without using antimicrobial chemicals are needed
      to prevent the spread of antibiotic resistance genes and disruption of microbial
      activities in biological treatment. This study developed an environmentally
      friendly biofouling resistant membrane by incorporating d-tyrosine onto a
      commercial nanofiltration membrane using FAU type zeolite nanoparticles that
      covalently bound to the membrane surface as carriers for slow release. The d
      tyrosine loaded membrane had similar water permeability as the unmodified
      membrane, but greatly reduced initial cell attachment and strongly inhibited
      subsequent biofilm formation without inactivating the bacteria. The membrane
      slowly released d-tyrosine in the time course of over 5 days, and retained its
      anti-biofouling capability in repeated 24 h efficacy tests for as long as 6 days.
      In nanofiltration operation, the d-tyrosine incorporated zeolite coating
      completely inhibited cell adhesion on the membrane surface and significantly
      alleviated membrane flux decline.

PMID- 29202343
TI  - Interactive effects of water quality, physical habitat, and watershed
      anthropogenic activities on stream ecosystem health.
AB  - Ecological degradation of streams remains a major environmental concern
      worldwide. While stream restoration has received considerable attention,
      mitigation efforts focused on the improvement of physical habitat have not proven
      completely effective. Several small-scale studies have emphasized that effective
      restoration strategies require a more holistic understanding of the variables at
      play, although the generalization of the findings based on the small-scale
      studies remains unclear. Using a comprehensive statewide stream monitoring
      database from West Virginia (WV), a detailed landscape dataset, and a machine
      learning algorithm, this study explores the interactive impacts of water quality
      and physical habitat on stream ecosystem health as indicated by benthic
      macroinvertebrate scores. Given the long history of energy extraction in this
      region (i.e., coal mining and oil/gas production), investigation of energy
      extraction influences is highlighted. Our results demonstrate that a combination
      of good habitat and low specific conductance is generally associated with
      favorable benthic macroinvertebrate scores, whereas poor habitat combined with
      water quality conditions typically indicative of high ionic strength are
      associated with impaired stream status. In addition, streams impacted by both
      energy extraction and residential development had a higher percentage of
      impairment compared to those impacted predominantly by energy extraction or
      residential development alone. While water quality played a more important role
      in the ecosystem health of streams impacted primarily by energy extraction
      activities, habitat seems to be more influential in streams impacted by
      residential development. Together, these findings emphasize that stream
      restoration strategies should consider interactive effects of multiple
      environmental stressors tailored to specific sites or site types - as opposed to
      considering a single stressor or multiple stressors separately.

PMID- 29202344
TI  - Simultaneous improvement of waste gas purification and nitrogen removal using a
      novel aerated vertical flow constructed wetland.
AB  - Insufficient oxygen supply is identified as one of the major factors limiting
      organic pollutant and nitrogen (N) removal in constructed wetlands (CWs). This
      study designed a novel aerated vertical flow constructed wetland (VFCW) using
      waste gas from biological wastewater treatment systems to improve pollutant
      removal in CWs, its potential in purifying waste gas was also identified.
      Compared with unaerated VFCW, the introduction of waste gas significantly
      improved NH4+-N and TN removal efficiencies by 128.48 +/- 3.13% and 59.09 +/-
      2.26%, respectively. Furthermore, the waste gas ingredients, including H2S, NH3,
      greenhouse gas (N2O) and microbial aerosols, were remarkably reduced after
      passing through the VFCW. The removal efficiencies of H2S, NH3 and N2O were 77.78
      +/- 3.46%, 52.17 +/- 2.53%, and 87.40 +/- 3.89%, respectively. In addition, the
      bacterial and fungal aerosols in waste gas were effectively removed with removal
      efficiencies of 42.72 +/- 3.21% and 47.89 +/- 2.82%, respectively. Microbial
      analysis results revealed that the high microbial community abundance in the
      VFCW, caused by the introduction of waste gas from the sequencing batch reactor
      (SBR), led to its optimized nitrogen transformation processes. These results
      suggested that the VFCW intermittently aerated with waste gas may have potential
      application for purifying wastewater treatment plant effluent and waste gas,
      simultaneously.

PMID- 29202345
TI  - Effective removal of bromate in nitrate-reducing anoxic zones during managed
      aquifer recharge for drinking water treatment: Laboratory-scale simulations.
AB  - The removal of bromate (BrO3-) as a by-product of ozonation in subsequent managed
      aquifer recharge (MAR) systems, specifically in anoxic nitrate (NO3-)-reducing
      zones, has so far gained little attention. In this study, batch reactors and
      columns were used to explore the influence of NO3- and increased assimilable
      organic carbon (AOC) due to ozonation pre-treatment on BrO3- removal in MAR
      systems. 8 m column experiments were carried out for 10 months to investigate
      BrO3- behavior in anoxic NO3--reducing zones of MAR systems. Anoxic batch
      experiments showed that an increase of AOC promoted microbial activity and
      corresponding BrO3- removal. A drastic increase of BrO3- biodegradation was
      observed in the sudden absence of NO3- in both batch reactors and columns,
      indicating that BrO3- and NO3- competed for biodegradation by denitrifying
      bacteria and NO3- was preferred as an electron acceptor under the simultaneous
      presence of NO3- and BrO3-. However, within 75 days' absence of NO3- in the
      anoxic column, BrO3- removal gradually decreased, indicating that the presence of
      NO3- is a precondition for denitrifying bacteria to reduce BrO3- in NO3--reducing
      anoxic zones. In the 8 m anoxic column set-up (retention time 6 days), the BrO3-
      removal achieved levels as low as 1.3 MUg/L, starting at 60 MUg/L (98% removal).
      Taken together, BrO3- removal is likely to occur in vicinity of NO3--reducing
      anoxic zones, so MAR systems following ozonation are potentially effective to
      remove BrO3-.

PMID- 29202346
TI  - Storage effects on quantity and composition of dissolved organic carbon and
      nitrogen of lake water, leaf leachate and peat soil water.
AB  - This study aimed to evaluate the effects of freezing and cold storage at 4 
      degrees C on bulk dissolved organic carbon (DOC) and nitrogen (DON) concentration
      and SEC fractions determined with size exclusion chromatography (SEC), as well as
      on spectral properties of dissolved organic matter (DOM) analyzed with
      fluorescence spectroscopy. In order to account for differences in DOM composition
      and source we analyzed storage effects for three different sample types,
      including a lake water sample representing freshwater DOM, a leaf litter leachate
      of Phragmites australis representing a terrestrial, 'fresh' DOM source and
      peatland porewater samples. According to our findings one week of cold storage
      can bias DOC and DON determination. Overall, the determination of DOC and DON
      concentration with SEC analysis for all three sample types were little
      susceptible to alterations due to freezing. The findings derived for the sampling
      locations investigated here may not apply for other sampling locations and/or
      sample types. However, DOC size fractions and DON concentration of formerly
      frozen samples should be interpreted with caution when sample concentrations are
      high. Alteration of some optical properties (HIX and SUVA254) due to freezing
      were evident, and therefore we recommend immediate analysis of samples for
      spectral analysis.

PMID- 29202347
TI  - Butt Why? Exploring factors associated with cigarette scavenging behaviors among
      adult smokers enrolling in a clinical trial for smoking cessation.
AB  - INTRODUCTION: Cigarette smoking is associated with many adverse health effects
      and is an important public health concern. Increased understanding of smokers'
      behavior is central to developing effective interventions. Cigarette scavenging,
      a behavior that involves smoking shared or previously used cigarettes has thus
      far only been shown to be prevalent among homeless or incarcerated populations.
      The current study examines whether cigarette scavenging is prevalent in a more
      general population of adult smokers enrolling in a smoking cessation clinical
      trial, and whether engagement in this behavior is associated with demographic or
      smoking-related psychosocial factors. METHODS: Baseline data was obtained from
      adult smokers (N=227) enrolling in a randomized clinical trial for smoking
      cessation. Cigarette scavenging was assessed using three items: a) sharing a
      cigarette with a stranger; b) smoking a "found" cigarette and c) smoking a
      previously used cigarette "butt". Participants who endorsed engaging in at least
      one of these three behaviors were categorized as a scavenger. RESULTS:
      Approximately 32% of participants endorsed at least one cigarette scavenging
      behavior. A multiple logistic regression analysis found that scavengers were more
      likely to be: men (p<0.001), of younger age at smoking onset (p=0.012),
      unemployed (p=0.003), more likely to have used marijuana in the past 30days
      (p=0.005), single or living alone (p=0.003), and to have experienced higher
      withdrawal symptoms during previous quit attempts (p=0.044) as compared to non
      scavengers. CONCLUSIONS: Scavenging is common among adult smokers. Interventions
      that address cigarette scavenging behaviors may better meet the needs of this
      unique smoking subgroup.

PMID- 29202348
TI  - Upper lip reconstruction using a pedicel superficial temporal artery flap.
AB  - INTRODUCTION: The hair-bearing superficial temporal artery free flap has been
      used in men for total upper lip reconstruction. In this paper we present a case
      of a partial upper lip defect in a man that was reconstructed with a pedicle
      superficial temporal artery flap. PRESENTATION OF CASE: Following a car accident,
      a 35-year old man sustained a partial upper defect. The defect included the
      entire "outer lamella" (i.e. the skin and red lip) of the right hemi-lip as well
      as the outer part of the muscle (i.e. partial defect of the middle lamella). A
      pedicle superficial temporal artery flap was raised and utilized to reconstruct
      the upper lip defect. There were no post-operative complications. The cosmetic
      and functional outcomes were excellent. DISCUSSION: The hair-bearing pedicle
      superficial temporal artery flap is commonly used for eye-brow and beard
      reconstruction. Free superficial temporal artery flaps have also been utilized to
      reconstruct total upper lip defects. For the first time in the literature, our
      report introduces the use of the pedicle flap in partial upper lip defects.
      CONCLUSION: We demonstrate that the pedicle flap is much simpler than the free
      flap and is adequate for reconstruction of partial upper lip defects. We also
      demonstrate a good cosmetic and functional outcome; and highlight several
      technical points to ensure a satisfactory outcome.

PMID- 29202349
TI  - Chondrometaplasia of the vocal cord in an adult male.
AB  - INTRODUCTION: (Chondrometaplasia of the larynx is a rare disease. We report a
      case that presented at the otolaryngology department in our institute in 2015.)
      PRESENTATION OF CASE: A 62year old man without any history of trauma presented
      with progressive dysphonia, dyspnoea, without any dysphagia. A fibreoptic
      laryngoscopic examination revealed nodular mass arising at the junction of
      anterior 1/3rd and posterior 2/3rd of left vocal cord. DISCUSSION: A computed
      tomography scan of the neck region showed a rounded and circumscribed mass
      without infiltration of the surrounding tissues. Histological investigation of
      the lesion revealed the presence of fibroelastic cartilaginous tissue, surrounded
      by a thin rim of fibrous tissue, with rare hypercellular areas, occasional
      binucleated cells, slight hyperchromasia, and an irregular nuclear profile.
      Mitotic activity was absent. CONCLUSION: The patient didn't have history of
      laryngeal trauma. Subacute and progressive onset of clinical symptoms and
      histological and radiological findings helps to distinguish the
      chondrometaplastic nature from true laryngeal cartilaginous tumours, such as
      chondroma and low grade chondrosarcoma.

PMID- 29202350
TI  - Case report: Ectopic Cushing's syndrome in a young male with hidden lung
      carcinoid tumor.
AB  - INTRODUCTION: Ectopic Cushing syndrome is a form of Cushing's in which a tumor
      outside the pituitary gland produces adrenocorticotropic hormone (ACTH). Small
      cell carcinoma and carcinoid of the lung comprises half of its cases. The main
      purpose of this study is to present a case of ectopic Cushing syndrome caused by
      a hidden lung carcinoid and how to manage it. PRESENTATION OF CASE: Here we
      present a case of a 26year old young male complains of increased weight and
      appetite, proximal muscle weakness, easy bruising and appearing of purple striae
      on his abdomen, with a final diagnosis of ACTH secreting lung carcinoid.
      DISCUSSION: The diagnosis was made by non-invasive radiological procedures (CT
      scan and MRI) and serological tests. The management consisted of medical
      treatment which was not useful, then bilateral adrenalectomy to limit the patient
      symptoms. The ectopic spot was finally detected and excised surgically through
      thoracotomy. After six months of follow up there was no recurrence, signs and
      symptoms of Cushing syndrome begin to disappear. CONCLUSION: Ectopic cushing
      syndrome is a complicated medical problem especially when it comes to
      identification of the ectopic spot. The surgical treatment could be curative when
      the spot is determined.

PMID- 29202351
TI  - Psoas abscess masquerading as a prosthetic hip infection: A case report.
AB  - INTRODUCTION: Psoas abscess is an unusual condition and is defined as a
      collection of pus in the iliopsoas compartment. Due to the unique anatomy of
      psoas muscle it forms a conduit for spread of infection from upper part of body
      to hip joint in neglected cases. CASE PRESENTATION: A 67year old lady presented
      with left groin pain for three weeks. She underwent an uncemented unipolar
      hemiarthoplasty eight years back. Currently, she developed fever and was unable
      to do any active left hip range of motion. Passive motion of the left hip was
      restricted to 30 degrees  flexion, no internal rotation, 5 degrees  external
      rotation, and 10 degrees  abduction. Lab workup showed raised serum infective
      markers and radiographs of pelvis were normal with no evidence of any
      radiolucency. Ultrasound guided aspiration of left hip joint showed E coli.
      Arthrotomy revealed clear fluid in hip joint but pus was drained at psoas
      insertion. Later on, culture reported presence of E. coli and biopsy confirmed
      psoas abscess. Postoperatively CT scan abdomen showed pyelonephritis. Antibiotics
      were given for three months. Twenty months later, she remains asymptomatic
      without evidence of infection with normal gait. DISCUSSION: Psoas abscess is a
      rare clinical entity that may mimic symptoms of a primary prosthetic hip
      infection. Treatment outcomes are directly related to early detection with
      adequate dissection of the psoas muscle up to sites of attachment and complete
      eradication of infection. CONCLUSION: This case highlights importance of thorough
      initial clinical examination, lab workup and radiological assessment to rule out
      rare causes of hip joint pain.

PMID- 29202352
TI  - Intrahepatic portal vein thrombosis due to postoperative biliary obstruction
      successfully treated by a partial thrombectomy combined with thrombolytic drug
      therapy.
AB  - INTRODUCTION: This case report aims to inform pancreatic surgeons about our
      perioperative management of intrahepatic portal vein thrombosis caused by an
      obstruction of hepaticojejunostomy (HJ) after pancreaticoduodenectomy (PD). CASE
      PRESENTATION: A 65-year-old woman was diagnosed with pancreas head carcinoma
      involving the superior mesenteric vein (SMV). Pancreaticoduodenectomy combined
      with SMV resection was followed by HJ. Twisting or narrowing was not evident
      during anastomosis. Total bilirubin values progressively increased to 13mg/dL on
      day 5. At that time, we suspected anastomotic occlusion and found complete portal
      thrombosis of the left liver. Therefore, emergency re-anastomosis of the HJ was
      followed by thrombectomy, which was not completely successful and did not
      completely recover initial portal flow. Thrombolytic drugs improved obstructive
      jaundice, eradicated the organized thrombosis and recovered the portal flow by
      day 30. The post-operative course was uneventful. DISCUSSION: A thrombosis
      immediately formed in the portal vein due to biliary obstruction of an
      anastomotic site. We speculated that biliary dilation and related inflammation
      caused a relative increase in arterial flow and decreased portal flow at the
      localized part of the umbilical portion. Although early surgical thrombectomy was
      attempted soon after the primary operation, the organized thrombosis persisted.
      However, thrombolytic therapy eradicated the thrombosis. CONCLUSION: Careful
      anastomosis of HJ during PD was necessary to avoid postoperative biliary
      stricture. This type of complication affects intrahepatic blood flow,
      particularly via the portal vein. Although immediate re-anastomosis or
      thrombectomy is applied, organized thrombosis cannot always be surgically
      removed.

PMID- 29202353
TI  - Giant interparietal inguinal hernia with undescended testis-A Rare case report.
AB  - INTRODUCTION: An interparietal inguinal hernia is a rare form of hernia. In this
      type of hernia, the sac passes between the layers of the abdominal wall of the
      inguinal canal area. Although its treatment is very simple but pre-operative
      diagnosis is really a challenging issue. PRESENTATION OF CASE: A 62 years old
      male patient presented with complaint of a large swelling over right lower
      abdomen with absence of right testes since birth. The lump was measured 26*22cm
      in size. Ultrasonography (USG) and Contrast enhanced computed Tomography (CECT)
      failed to diagnose as interparietal inguinal hernia which was proved intra
      operatively. Few cases have been reported in the medical literature like this.
      DISCUSSION: Exploration revealed the large abdominal lump presenting as an
      interparietal inguinal hernia. Hernia sac was lying in between external &
      internal oblique muscles. The right testis was intraabdominal & atrophied. The
      external inguinal ring was almost completely obstructed. CONCLUSION: An
      interparietal hernia with undescended testis is a very rare presentation. Even
      with USG & CT scan diagnosis is very challenging and final diagnosis can be made
      only intraoperatively.

PMID- 29202354
TI  - Silica-covered star-shaped Au-Ag nanoparticles as new electromagnetic
      nanoresonators for Raman characterisation of surfaces.
AB  - One of the tools used for determining the composition of surfaces of various
      materials is shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS).
      SHINERS is a modification of "standard" surface-enhanced Raman spectroscopy
      (SERS), in which, before Raman spectra are recorded, the surfaces analysed are
      covered with a layer of plasmonic nanoparticles protected by a very thin layer of
      a transparent dielectric. The plasmonic cores of the core-shell nanoparticles
      used in SHINERS measurements generate a local enhancement of the electric field
      of the incident electromagnetic radiation, whereas the transparent coatings
      prevent the metal cores from coming into direct contact with the material being
      analysed. In this contribution, we propose a new type of SHINERS nanoresonators
      that contain spiky, star-shaped metal cores (produced from a gold/silver alloy).
      These spiky, star-shaped Au-Ag nanoparticles have been covered by a layer of
      silica. The small radii of the ends of the tips of the spikes of these plasmonic
      nanostructures make it possible to generate a very large enhancement of the
      electromagnetic field there, with the result that such SHINERS nanoresonators are
      significantly more efficient than the standard semi-spherical nanostructures. The
      Au-Ag alloy nanoparticles were synthesised by the reduction of a solution
      containing silver nitrate and chloroauric acid by ascorbic acid. The final
      geometry of the nanostructures thus formed was controlled by changing the ratio
      between the concentrations of AuCl4- and Ag+ ions. The shape of the synthesised
      star-shaped Au-Ag nanoparticles does not change significantly during the two
      standard procedures for depositing a layer of silica (by the decomposition of
      sodium silicate or the decomposition of tetraethyl orthosilicate).

PMID- 29202355
TI  - Preparation of cellophane-based substrate and its SERS performance on the
      detection of CV and acetamiprid.
AB  - Cellophane was taken as platform to fabricate a new SERS substrate via silver
      mirror action. From Raman spectra, it can be found that the Raman signal of Ag
      coated cellophane has little influence on the detection of analytes molecules.
      Raman mapping analysis showed that the cellophane-based SERS substrate has good
      uniformity. By using the Ag-coated cellophane, 10-6-10-9M crystal violet (CV)
      could be detected by this substrate and the reproducibility of the substrate was
      also involved. Acetamiprid was also detected via Ag-coated cellophane. The result
      showed that cellophane is suitable to be taken as platform for preparation of
      SERS substrates.

PMID- 29202356
TI  - Apraxia of object-related action does not depend on visual feedback.
AB  - Pantomime of tool use is typically affected in neurological patients with
      apraxia, while at the same time these patients are able to perform the use of the
      actual tool with less or no errors. This discrepancy is commonly explained by
      differences in afferent input, in particular a lack of visual online feedback
      from the object in pantomime. The present study investigated the role of visual
      feedback in apraxia of pantomime by testing neurological patients with apraxia
      and healthy controls in a task requiring the pantomime of tool use as well as
      real tool use. Visual feedback was systematically removed at different phases of
      the action using shutter glasses that were controlled online based on real-time
      motion-capturing. Data analyses revealed more errors in pantomime than in real
      tool use. These differences were similar in patients as well as in controls.
      Removal of visual feedback did not affect apractic errors specifically; it
      neither increased patients' apractic errors during pantomime of tool use nor
      transformed the patients' normal movements with a real tool into movements with
      apractic errors. Our findings contradict the hypothesis that apraxia patients
      pathologically over-rely on visual feedback. Instead, we propose that pantomime
      of tool use requires cognitive processes that are not necessary for real tool use
      and independent of visual online feedback.

PMID- 29202358
TI  - Increasing mediolateral standing sway is associated with increasing corticospinal
      excitability, and decreasing M1 inhibition and facilitation.
AB  - In standing, corticospinal excitability increases and primary motor cortex (M1)
      inhibition decreases in response to anterior posterior or direction unspecific
      manipulations that increase task difficulty. However, mediolateral (ML) sway
      control requires greater active neural involvement. Therefore, the primary
      purpose of this study was to determine the pattern of change in neural
      excitability when ML postural task difficulty is manipulated and to test whether
      the neural excitability is proportional to ML sway magnitude across conditions.
      Tibialis anterior corticospinal excitability was quantified using motor evoked
      potential (MEP) and postural sway was indexed using ML center of pressure (COP)
      velocity. Additionally, we examined inhibition and facilitation processes in the
      primary motor cortex using the paired pulse short interval intracortical
      inhibition (SICI) and intracortical facilitation (ICF) techniques respectively.
      Measurements were repeated in four conditions with quiet stance as a control.
      Differences between conditions were tested using one-way repeated measures
      ANOVAs, on log transformed data. Associations were quantified using Spearman's
      Rank Correlation Coefficient. There was a significant main effect of condition on
      all the neural excitability measures with MEP (p<0.001) being highest in the most
      difficult condition, and SICI (p=0.01), ICF (p<0.001) being lowest in the most
      difficult condition. Increasing ML COP velocity was significantly associated with
      increasing MEP amplitude (r=0.68, p<0.001), but decreasing SICI (r=0.24, p=0.03)
      and ICF (r=-0.54, p<0.001). Our results show that both corticospinal and M1
      excitability in standing are scaled in proportion to ML task difficulty.

PMID- 29202357
TI  - Effect of parameter selection on entropy calculation for long walking trials.
AB  - It is sometimes difficult to obtain uninterrupted data sets that are long enough
      to perform nonlinear analysis, especially in pathological populations. It is
      currently unclear as to how many data points are needed for reliable entropy
      analysis. The aims of this study were to determine the effect of changing
      parameter values of m, r, and N on entropy calculations for long gait data sets
      using two different modes of walking (i.e., overground versus treadmill).
      Fourteen young adults walked overground and on a treadmill at their preferred
      walking speed for one-hour while step time was collected via heel switches.
      Approximate (ApEn) and sample entropy (SampEn) were calculated using multiple
      parameter combinations of m, N, and r. Further, r was tested under two cases
      r*standard deviation and r constant. ApEn differed depending on the combination
      of r, m, and N. ApEn demonstrated relative consistency except when m=2 and the
      smallest r values used (rSD=0.015*SD, 0.20*SD; rConstant=0 and 0.003). For
      SampEn, as r increased, SampEn decreased. When r was constant, SampEn
      demonstrated excellent relative consistency for all combinations of r, m, and N.
      When r constant was used, overground walking was more regular than treadmill.
      However, treadmill walking was found to be more regular when using rSD for both
      ApEn and SampEn. For greatest relative consistency of step time data, it was best
      to use a constant r value and SampEn. When using entropy, several r values must
      be examined and reported to ensure that results are not an artifact of parameter
      choice.

PMID- 29202359
TI  - Integrated pharmacokinetics of ginsenosides after intravenous administration of
      YiQiFuMai powder injection in rats with chronic heart failure by UFLC-MS/MS.
AB  - YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese
      medicine (TCM) formula Shengmai San, is a modern preparation widely used to
      combat cardiovascular diseases, chronic heart failure (CHF) for example, in
      clinical practice in China. Ginsenosides are the major components of YQFM, which
      are responsible for its therapeutic effect. In this research, we developed a
      rapid, sensitive and simple method for simultaneous determination of ten
      ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography
      tandem mass spectrometry (UFLC-MS/MS). After solid phase extraction (SPE),
      chromatography was done on an Acquity UPLC HSS T3 column (1.8MUm, 100mm*2.1mm,
      i.d.) through an 8.0min gradient elution with acetonitrile and 0.1% formic acid
      in water, while mass spectrometry was performed in the positive ion electrospray
      ionization (ESI) mode. A good linearity was achieved for each analyte with
      correlation coefficient (r) >0.9920. The lower limits of quantification (LLOQ)
      were 1.25ng/mL for ginsenoside Rg1, Rd, Re and Rh1, 2.5ng/mL for ginsenoside Rf,
      Rg3, Rb2 and Rb3 and 5.0ng/mL for ginsenoside Rb1 and Rc, respectively. All the
      precision (RSD) data ranged from 1.7-14.5% and the accuracy (RE) data was within
      +/-13.73%. Moreover, the validated method has been applied to investigate the
      integrated pharmacokinetic profiles of ginsenosides in CHF rats following
      intravenous administration of YQFM successfully.

PMID- 29202360
TI  - Enhanced capillary electrophoretic screening of Alzheimer based on direct
      apolipoprotein E genotyping and one-step multiplex PCR.
AB  - Human apolipoprotein E (ApoE) is associated with high cholesterol levels,
      coronary artery disease, and especially Alzheimer's disease. In this study, we
      developed an ApoE genotyping and one-step multiplex polymerase chain reaction
      (PCR) based-capillary electrophoresis (CE) method for the enhanced diagnosis of
      Alzheimer's. The primer mixture of ApoE genes enabled the performance of direct
      one-step multiplex PCR from whole blood without DNA purification. The combination
      of direct ApoE genotyping and one-step multiplex PCR minimized the risk of DNA
      loss or contamination due to the process of DNA purification. All amplified PCR
      products with different DNA lengths (112-, 253-, 308-, 444-, and 514-bp DNA) of
      the ApoE genes were analyzed within 2min by an extended voltage programming (VP)
      based CE under the optimal conditions. The extended VP-based CE method was at
      least 120-180 times faster than conventional slab gel electrophoresis methods In
      particular, all amplified DNA fragments were detected in less than 10 PCR cycles
      using a laser-induced fluorescence detector. The detection limits of the ApoE
      genes were 6.4-62.0pM, which were approximately 100-100,000 times more sensitive
      than previous Alzheimer's diagnosis methods In addition, the combined one-step
      multiplex PCR and extended VP-based CE method was also successfully applied to
      the analysis of ApoE genotypes in Alzheimer's patients and normal samples and
      confirmed the distribution probability of allele frequencies. This combination of
      direct one-step multiplex PCR and an extended VP-based CE method should increase
      the diagnostic reliability of Alzheimer's with high sensitivity and short
      analysis time even with direct use of whole blood.

PMID- 29202361
TI  - A novel adenine-releasing assay for ribosome-inactivating proteins.
AB  - Ribosome-inactivating proteins (RIPs) are toxic enzymes that are mostly
      biosynthesized by plants. RIPs are N-glycosidases that cleave an essential
      adenine molecule from the 28S rRNA. This is followed by the irreversible
      inhibition of protein synthesis leading to cell death. By fusing RIPs to cancer
      cell specific targeting ligands RIPs have been utilized for targeted anti-tumor
      therapy. The anti-tumoral efficiency of such conjugates depends significantly on
      the N-glycosidase activity of the RIP domain. Different methods have been
      developed in order to determine the N-glycosidase activity of RIPs and RIP domain
      containing anti-tumor toxins. However the existing methods are elaborate and
      include radioassays, HPLC and enzymatic conversion assays. Here, a simple and
      cost effective N-glycosidase assay is presented, which is based on the direct
      determination of the released adenine by thin-layer chromatography (TLC) and TLC
      densitometry. An adenine based single stranded oligonucleotide is used as
      substrate. Following TLC development the released adenine is quantified on silica
      glass plates by UV absorbance at 260nm.

PMID- 29202362
TI  - Multi-residue analysis of sedative drugs in human plasma by ultra-high
      performance liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: Sedative drugs are often used for the treatment of depression,
      anxiety and insomnia and they are involved in many forensic cases. This work
      established a method for the simultaneous determination of multi-groups of
      sedative drugs (benzodiazepines, barbitals, phenothiazines, tricyclic
      antidepressant and butyrophenone) in human plasma for forensic analysis. A large
      number of sedative drugs with forensic interest can be analyzed in a short time
      with lower limits of quantification by combination of SPE extraction and ultra
      performance liquid chromatography-tandem mass spectrometry. METHODS: Sample
      preparation consisted of extraction of the plasma by hydrochloric acid solution
      and further purified by SLW solid phase extraction column. RESULTS: The method
      was fully validated to cover large concentration ranges of 50-1000MUg/L for 5
      Barbital drugs, while 1.0-50MUg/L for the other 14 sedative drugs. The average
      recoveries of the drugs spiked at three levels ranged from 65.3% to 114.3% with
      the relative standard deviation between 1.2% and 13.2%. The lowest limits of
      quantification (LLOQ) were 100MUg/L for Barbital drugs and1.0MUg/L for all the
      other 14 drugs. CONCLUSIONS: This validated method has been successfully used in
      emergency analysis of multi-residues of sedative drugs in plasma.

PMID- 29202363
TI  - Quantification of glycocholic acid in human serum by stable isotope dilution
      ultra performance liquid chromatography electrospray ionization tandem mass
      spectrometry.
AB  - A rapid, accurate and sensitive stable isotope dilution ultra performance
      liquidchromatography electrospray ionization tandem mass spectrometry (ID-UPLC
      ESI-MS/MS) method for the determination of glycocholic acid (GCA) in human serum
      was developed and validated. Serum samples were spiked with D5-glycocholic acid
      and then pretreated with protein precipitation. The analysis was performed on a
      Waters BEH C18 column (100 mm*2.1mm, 1.7MUm), followed by ESI-MS/MS detection in
      negative ion mode under multiple reaction monitoring mode. The calibration curves
      covered a concentration range from 0.2 to 400ng/mL. The limit of detection and
      limit of quantification was 0.01ng/mL and 0.05ng/mL, respectively. The method
      showed satisfactory precision on intra-day (2.3-6.1%) and inter-day (2.4-4.6%)
      analyses and achieved good recovery at three spiked levels (103.7-114.3%).
      Moreover, this established method was successfully applied for quantification of
      GCA in serum samples from healthy volunteers, patients with hepatocellular
      carcinoma (HCC) and patients with other cancers. We demonstrated that the level
      of GCA in patients with HCC was significantly higher not only than that in
      healthy controls, but also than that in patients with other cancer, whereas no
      significant difference of GCA level was observed between healthy control group
      and other cancers group.

PMID- 29202364
TI  - Perceptions of randomness in binary sequences: Normative, heuristic, or both?
AB  - When people consider a series of random binary events, such as tossing an
      unbiased coin and recording the sequence of heads (H) and tails (T), they tend to
      erroneously rate sequences with less internal structure or order (such as HTTHT)
      as more probable than sequences containing more structure or order (such as
      HHHHH). This is traditionally explained as a local representativeness effect:
      Participants assume that the properties of long sequences of random outcomes-such
      as an equal proportion of heads and tails, and little internal structure-should
      also apply to short sequences. However, recent theoretical work has noted that
      the probability of a particular sequence of say, heads and tails of length n,
      occurring within a larger (>n) sequence of coin flips actually differs by
      sequence, so P(HHHHH) <P(HTTHT). In this alternative account, people apply
      rational norms based on limited experience. We test these accounts. Participants
      in Experiment 1 rated the likelihood of occurrence for all possible strings of 4,
      5, and 6 observations in a sequence of coin flips. Judgments were better
      explained by representativeness in alternation rate, relative proportion of heads
      and tails, and sequence complexity, than by objective probabilities. Experiments
      2 and 3 gave similar results using incentivized binary choice procedures. Overall
      the evidence suggests that participants are not sensitive to variation in
      objective probabilities of a sub-sequence occurring; they appear to use
      heuristics based on several distinct forms of representativeness.

PMID- 29202365
TI  - Development of reduction scenarios for criteria air pollutants emission in Tehran
      Traffic Sector, Iran.
AB  - Transport-related pollution as the main source of air pollution must be reduced
      in Tehran mega-city. The performance of various developed scenarios including BAU
      (Business As Usual) as baseline scenario, ECV (Elimination of carburetor equipped
      Vehicle), NEM (New Energy Motorcycles), HES (Higher Emission Standard), VCR
      (Vehicle Catalyst Replacement), FQE (Fuel Quality Enhancement), DPF (Diesel
      Particulate Filter) and TSA (Total Scenarios Aggregation) are evaluated by
      International Vehicle Model up to 2028. In the short term, the ECV, VCR, and FQE
      scenarios provided high performance in CO, VOCs and NOx emissions control. Also
      FQE has an excellent effect on SOx emission reduction (86%) and DPF on PM
      emissions (20%). In the mid-term, the VCR, ECV, and FQE scenarios were presented
      desirable mean emission reduction on CO, VOCs, and NOx. Moreover, NOx emission
      reduction of DPF scenario is the most common (14%). Again FQE scenario proves to
      have great effect on SOx emission reduction in mid-term (86%), DPF and HES
      scenarios on PM (DPF: 49% and HES: 17%). Finally for the long term, VCR, ECV,
      FQE, and NEM scenarios were shown good performance in emission control on CO,
      VOCs and NOx. For SOx only FQE has a good effect in all time periods (FQE: 86%)
      and DPF and HES scenarios have the best effect on PM emission reduction
      respectively (DPF: 51% and HES: 27%) compared with BAU scenario. However, DPF
      scenario increases 12% SOx emission in long-term (2028). It can be generally
      concluded that VCR and ECV scenarios would achieve a significant reduction on
      gaseous pollutants emission except for SOx in general and FQE scenarios have
      desirable performance for all gaseous pollutants in the short term and also for
      SOx and VOCs in long term. In addition, the DPF and HES would be desirable
      scenario for emission control on PM in Tehran Traffic Sector.

PMID- 29202366
TI  - Nutrient release and uptake by littoral macrophytes during water level
      fluctuations.
AB  - Water level drawdown followed by rewetting in reservoirs/lakes can shift
      macrophytes from a nutrient sink to a source, thus changing nutrient dynamics and
      causing water quality problems. However, there is limited understanding of the
      effect of macrophyte growth versus decomposition on nitrogen (N) and phosphorus
      (P) dynamics during water level fluctuations (WLFs). This study examined nutrient
      release versus uptake by two submerged macrophytes, the invasive Cabomba
      caroliniana (Cabomba) and the native Hydrilla verticillata (Hydrilla), compared
      to bare sediments, after drying then rewetting. Overall, we examined the nutrient
      dynamics in treatments comparing 1) two macrophyte species, 2) macrophyte
      nutrient uptake versus release, and 3) the presence of macrophytes versus bare
      sediments. Our study showed that Cabomba litter had a higher nutrient release
      rate and resulted in higher water column chlorophyll a concentrations compared
      with Hydrilla litter. The decomposition impact of both species on water column P
      concentrations was greater than that for N, and proportionally less P was
      assimilated than released by macrophytes compared with N. This resulted in P
      accumulation and a decreased N:P ratio in the water column compared to bare
      sediments without macrophytes. Phosphorus accumulation in the water column during
      macrophyte decomposition increased phytoplankton growth in our study,
      highlighting the potential for phytoplankton blooms, especially in P-deficient
      lakes. Regrown Hydrilla had a higher potential for assimilating sediment N
      compared to Cabomba. In contrast, regrown Cabomba was more efficient at reducing
      water column N compared with Hydrilla, suggesting different pathways of
      assimilation. Neither regrown Cabomba nor Hydrilla significantly reduced water
      column P concentrations. This study highlights different nutrient impacts of
      macrophyte beds compared to bare sediments during WLFs, and the role of regrown
      macrophytes in assimilating the released nutrients from macrophyte decomposition.
      However, the scale of their role is dependent on macrophyte species, forms of
      nutrients and drying-wetting regimes.

PMID- 29202367
TI  - Remediation of aged diesel contaminated soil by alkaline activated persulfate.
AB  - The present work studies the efficiency of alkaline activated persulfate (PS) to
      remediate an aged diesel fuel contaminated soil from a train maintenance
      facility. The Total Petroleum Hydrocarbon (TPH) concentration in soil was
      approximately 5000mgkg-1 with a ratio of aliphatic:aromatic compounds of 70:30.
      Aromatic compounds were mainly naphtalenes and phenanthrenes. The experiments
      were performed in batch mode where different initial concentrations of persulfate
      (105mM, 210mM and 420mM) and activator:persulfate ratios (2 and 4) were
      evaluated, with NaOH used as activator. Runs were carried out during 56days.
      Complete TPH conversion was obtained with the highest concentration of PS and
      activator, whereas in the other runs the elimination of fuel ranged between 60
      and 77%. Besides, the abatement of napthalenes and phenantrenes was faster than
      aliphatic reduction (i. e. after 4days of treatment, the conversions of the
      aromatic compounds were around 0.8 meanwhile the aliphatic abatements were 0.55)
      and no aromatic oxidation intermediates from naphtalenes or phenantrenes were
      detected. These results show that this technology is effective for the
      remediation of aged diesel in soil with alkaline pH.

PMID- 29202368
TI  - Mussels can both outweigh and interact with the effects of terrestrial to
      freshwater resource subsidies on littoral benthic communities.
AB  - Litterfall is an important resource subsidy for lake ecosystems that primarily
      accumulates in littoral zones. Bivalves are abundant within littoral zones and
      may modify the effects of terrestrial resource subsidies through trophic
      interactions and engineering their surrounding habitat. Leaf inputs to lakes and
      freshwater mussel abundances are changing throughout the boreal ecoregion so we
      set out to investigate how the co-occurring benthic community might respond. We
      set up an in situ mesocosm experiment in Ramsey Lake, Sudbury, ON, Canada.
      Mesocosms contained sediments of either 5% or 35% terrestrial organic matter
      (tOM), into which we placed mussels (Elliptio complanata) at differing densities
      (0, 0.4 and 2musselsm-2, with a sham mussel treatment at 0.4musselsm-2). Over one
      month we recorded the sediment chemistry (dissolved organic carbon, nitrogen and
      phosphorus), littoral organisms (benthic algae and zooplankton) and mussel
      growth. At high mussel densities we recorded a 90%, 80%, 45% and 40% reduction in
      phosphorus, dissolved organic carbon, nitrogen and benthic diatoms, respectively,
      whereas at low mussel densities we observed a 3-fold increase in zooplankton. We
      discuss that these results were caused by a combination of bioturbation and
      trophic interactions. Benthic diatom concentrations were also reduced by 20% in
      sediments of 35% tOM, likely due to shading and competition with bacteria. Mussel
      growth increased at high mussel densities but was offset at high tOM, likely due
      to the organic matter interfering with filter feeding. Our results suggest that
      mussels can alter the geochemical composition of sediments and abundances of
      associated littoral organisms, in some cases regardless of tOM quantity.
      Therefore, the dominant top-down control exerted by freshwater mussels may
      outweigh bottom-up effects of tOM additions. Generally, our study reveals the
      importance of considering dominant species when studying the effects of cross
      ecosystem resource fluxes.

PMID- 29202369
TI  - Identification of fine scale and landscape scale drivers of urban aboveground
      carbon stocks using high-resolution modeling and mapping.
AB  - Urban areas are sources of land use change and CO2 emissions that contribute to
      global climate change. Despite this, assessments of urban vegetation carbon
      stocks often fail to identify important landscape-scale drivers of variation in
      urban carbon, especially the potential effects of landscape structure variables
      at different spatial scales. We combined field measurements with Light Detection
      And Ranging (LiDAR) data to build high-resolution models of woody plant
      aboveground carbon across the urban portion of Brisbane, Australia, and then
      identified landscape scale drivers of these carbon stocks. First, we used LiDAR
      data to quantify the extent and vertical structure of vegetation across the city
      at high resolution (5*5m). Next, we paired this data with aboveground carbon
      measurements at 219 sites to create boosted regression tree models and map
      aboveground carbon across the city. We then used these maps to determine how
      spatial variation in land cover/land use and landscape structure affects these
      carbon stocks. Foliage densities above 5m height, tree canopy height, and the
      presence of ground openings had the strongest relationships with aboveground
      carbon. Using these fine-scale relationships, we estimate that 2.2+/-0.4 TgC are
      stored aboveground in the urban portion of Brisbane, with mean densities of
      32.6+/-5.8MgCha-1 calculated across the entire urban land area, and 110.9+/
      19.7MgCha-1 calculated within treed areas. Predicted carbon densities within
      treed areas showed strong positive relationships with the proportion of
      surrounding tree cover and how clumped that tree cover was at both 1km2 and 1ha
      resolutions. Our models predict that even dense urban areas with low tree cover
      can have high carbon densities at fine scales. We conclude that actions and
      policies aimed at increasing urban carbon should focus on those areas where urban
      tree cover is most fragmented.

PMID- 29202370
TI  - Endocrine effects after ozonation of tamoxifen.
AB  - Ozonation is used as additional wastewater treatment option to remove
      recalcitrant micropollutants. It also removes the estrogenic activity found in
      wastewater but not always the anti-estrogenic activity. This can be explained by
      an incomplete removal of anti-estrogenic micropollutants or by formation of
      transformation products (TPs) which retain the activity. The present study
      investigates the degradation of the anti-estrogenic pharmaceutical tamoxifen in
      pure water, regarding TP formation and related anti-estrogenic effect using
      Arxula adeninivorans yeast estrogen screen (A-YES). In total, five transformation
      products were detected: three N-oxides and two further products (TP 270 and TP
      388). For the transformation product TP 270 a correlation of the extent of
      formation with an increase of the anti-estrogenic activity was determined,
      demonstrating that transformation products from ozonation can be more active in a
      bioassay than the parent compounds. Our study shows also that the transformation
      of tamoxifen to N-oxides reduces the anti-estrogenic activity. The reactivity of
      amines towards ozone typically increases with pH, since only deprotonated amines
      react with ozone. Hence, removal of the endocrine activity by N-oxide formation
      may be disfavored at low pH.

PMID- 29202371
TI  - Application of the 15N tracer method to study the effect of pyrolysis temperature
      and atmosphere on the distribution of biochar nitrogen in the biomass-biochar
      plant system.
AB  - Biochar nitrogen is key to improving soil fertility, but the distribution of
      biochar nitrogen in the biomass-biochar-plant system is still unclear. To provide
      clarity, the 15N tracer method was utilised to study the distribution of biochar
      nitrogen in the biochar both before and after its addition to the soil. The
      results can be summarised as follows. 1) The retention rate of 15N in biochar
      decreases from 45.23% to 20.09% with increasing pyrolysis temperature from 400 to
      800 degrees C in a CO2 atmosphere. 2) The retention rate of 15N in biochar
      prepared in a CO2 atmosphere is higher than that prepared in a N2 atmosphere when
      the pyrolysis temperature is below 600 degrees C. 3) Not only can biochar N
      slowly facilitate the adsorption of N by plants but the addition of biochar to
      the soil can also promote the supply of soil nitrogen to the plant; in contrast,
      the direct return of wheat straw biomass to the soil inhibits the absorption of
      soil N by plants. 4) In addition, the distribution of nitrogen was clarified;
      that is, when biochar was prepared by the pyrolysis of wheat straw at 400 degrees
      C in a CO2 atmosphere, the biochar retained 45.23% N, and after the addition of
      this biochar to the soil, 39.99% of N was conserved in the biochar residue, 4.55%
      was released into the soil, and 0.69% was contained in the wheat after growth for
      31days. Therefore, this study very clearly shows the distribution of nitrogen in
      the biomass-biochar-plant system.

PMID- 29202372
TI  - Groundwater chemistry and radon-222 distribution in Jerba Island, Tunisia.
AB  - The present study integrates hydrogeological, hydrochemical and radiogenic data
      of groundwater samples taken from the Plio-Quaternary unconfined aquifer of Jerba
      Island, southeastern Tunisia, in order to interpret the spatial variations of the
      groundwater quality and identify the main hydrogeochemical factors responsible
      for the high ion concentrations and radon-222 content in the groundwater
      analysed. Thirty-nine groundwater samples were collected from open wells
      widespread on the island. Physical parameters (EC, pH, TDS and T  degrees ) were
      measured, major ions (Ca2+, Mg2+, Na+, K+, Cl-, SO42-, NO3- and HCO3-) were
      analysed and 222Rn concentrations were determined using a RAD7-H2O.
      Hydrogeochemical characterisation revealed that groundwater from the Jerba
      aquifer has several origins. Basically, two water types exist in the island. The
      first one, characterized by a low to moderate salinity with a chemical facies
      CaMgClSO4, characterizes the central part of Jerba (a recharge area) due to
      carbonate and gypsum dissolution. The second water type with high salinities,
      dominated by NaKCl type, was observed in coastal areas and some parts having low
      topographic and piezometric levels. These areas seem to be affected by the
      seawater intrusion process. The 222Rn concentrations in groundwater samples in
      Jerba varied from 0 Bq.L-1 to 2860 Bq.L-1 with an average of 867 Bq.L-1. The
      highest values were registered in the western coastal wells and near the fault of
      Guellala. However, the central and eastern wells showed low radon levels.
      Compared to 222Rn activity in some countries with the same lithology, radon
      concentrations in the Jerba unconfined aquifer have higher values influenced by
      the structure of the aquifer and by seawater inflow enriched with 222Rn resulting
      from the decay of uranium derived from phosphogypsum deposits in the gulf of
      Gabes. The EC and 222Rn spatial variability in the study area were mapped using
      ARC Map 10.3 software. Hydrochemical results in addition to geological data and
      radon activities confirm the existence of vertical communication between the
      Miocene aquifer and the unconfined Plio-Quaternary aquifer through fault system
      and a lateral communication with the sea via seawater intrusion.

PMID- 29202373
TI  - Fate of 137Cs, 90Sr and 239+240Pu in soil profiles at a water recharge site in
      Basel, Switzerland.
AB  - An important process in the production of drinking water is the recharge of the
      withdrawn ground water with river water at protected recharge fields. While it is
      well known that undisturbed soils are efficiently filtering and adsorbing
      radionuclides, the goal of this study was to investigate their behaviour in an
      artificial recharge site that may receive rapid and additional input of
      radionuclides by river water (particularly when draining a catchment including
      nuclear power plants (NPP)). Soil profiles of recharge sites were drilled and
      analysed for radionuclides, specifically radiocesium (137Cs), radiostrontium
      (90Sr) and plutonium (239+240Pu). The distribution of the analysed radionuclides
      were compared with an uncultivated reference soil outside the recharge site. The
      main activity of 137Cs was located in the top soil (4.5-7.5 cm) and reached down
      to a depth of 84 cm and 48 cm for the recharge and the reference site,
      respectively. The found activities of 239+240Pu originate from the global fallout
      after 1950. 239+240Pu appeared to be strongly adsorbed onto soil particles. The
      shape of the depth profile was similar to 137Cs, but also similar between the
      recharge and the reference site. In contrast, 90Sr showed a uniform distribution
      over the entire depth of the recharge and reference profiles indicating that 90Sr
      already entered the gravel zone and the ground water. Elevated inventories of the
      radionuclides were observed for the recharge site. The soil of the recharge field
      exhibited a threefold higher activity of 137Cs compared to the reference soil.
      Also for 239+240Pu higher inventories where observed for the recharge sites
      (40%). 90Sr behaved differently, showing similar inventories between reference
      and recharge site. We estimate that 75-89% of the total inventory of 137Cs in the
      soil at the recharge site (7.000 Bq/m2) originated from the fallout of the
      Chernobyl accident and from emissions of Swiss NPPs. This estimate is based on
      the actual activity ratio of 137Cs/239+240Pu of 22 for global fallout. The
      investigations identified radiostrontium as potential threat to the ground water.

PMID- 29202374
TI  - Extraction and quantification system for environmental radioxenon sample
      analysis.
AB  - A xenon dynamic adsorption setup based on granular activated carbon packed column
      was developed. The adsorption behavior of xenon under different experimental
      conditions was studied and the results used to design an appropriate adsorber
      column for specific conditions. The resulting radioxenon gas extraction and
      quantification setup was evaluated based on an inter-comparison exercise and
      standard sample analysis results. The results showed that the quantification
      setup achieves experimental rules with uncertainty of +/-3%.

PMID- 29202375
TI  - Coronary versus carotid artery plaques. Similarities and differences regarding
      biomarkers morphology and prognosis.
AB  - Carotid and coronary artery disease are two major atherosclerotic conditions that
      have shown an increased prevalence in the last three decades that is associated
      with high morbidity and mortality. Recent data have revealed that the development
      of the atherosclerotic plaque-the basic entity in both diseases-may share similar
      characteristics and mechanisms irrespective of the location site. Even though the
      biology of atherosclerotic process is similar, there are differences in plaque
      morphology and characteristics. Indeed, plaque erosion, calcified nodules,
      fibrous cap thickness and macrophage accumulation may be different in the setting
      of coronary and carotid artery disease. The perivascular adipose tissue
      surrounding the coronary arteries (but not carotids) could also affect plaque
      biology. In this review we focus on comparative the characteristics of both types
      of atherosclerotic plaques and summarize existing knowledge to provide useful
      conclusions about current and future treatment strategies.

PMID- 29202376
TI  - Circadian rhythm in idiopathic normal pressure hydrocephalus.
AB  - OBJECTIVES: The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH)
      takes place in structures close to the cerebral ventricular system.
      Suprachiasmatic nucleus (SCN), situated close to the third ventricle, is involved
      in circadian rhythm. Diurnal disturbances are well-known in demented patients.
      The cognitive decline in iNPH is potentially reversible after a shunt operation.
      Diurnal rhythm has never been studied in iNPH. We hypothesize that there is a
      disturbance of circadian rhythm in iNPH-patients and the aim was to study any
      changes of the diurnal rhythm (mesor and circadian period) as well as any changes
      of the diurnal amplitude and acrophase of the activity in iNPH-patients before
      and after a shunt operation. PATIENTS AND METHODS: Twenty consecutive iNPH
      patients fulfilling the criteria of the American iNPH-guidelines, 9 males and 11
      females, mean age 73 (49-81) years were included. The patients underwent a pre
      operative clinical work-up including 10m walk time (w10mt) steps (w10ms), TUG
      time (TUGt) and steps (TUGs) and for cognitive function an MMSE score was
      measured. In order to receive circadian rhythm data actigraphic recordings were
      performed using the SenseWear 2 (BodyMedia Inc Pittsburgh, PA, USA) actigraph.
      Cosinor analyses of accelerometry data were performed in "R" using non-linear
      regression with Levenburg- Marquardt estimation. Pre- and post-operative data
      regarding mesor, amplitude and circadian period were compared using Wilcoxon-Mann
      Whitney test for paired data. RESULTS: Twenty patients were evaluated before and
      three month post-operatively. Motor function (w10mt, w10ms, TUGt, TUGs) was
      significantly improved while MMSE was not significantly changed. Actigraphic
      measurements (mesor, amplitude and circadian period) showed no significant
      changes after shunt operation. CONCLUSION: This is the first systematic study of
      circadian rhythm in iNPH-patients. We found no significant changes in circadian
      rhythm after shunt surgery. The conceptual idea of diurnal rhythm changes in
      hydrocephalus is still interesting from a theoretical standpoint and warrants
      further studies that could include a combination of better designed actigraphic
      studies in combination with neuroendocrine markers and imaging methods.

PMID- 29202377
TI  - Quantifying the prognostic significance in glioblastoma of seizure history at
      initial presentation: A systematic review and meta-analysis.
AB  - The role of prognostic factors in the management of glioblastoma (GBM) is very
      important given the stasis in improving its clinical outcomes. Patients who
      initially present with a positive seizure history at diagnosis have anecdotally
      experienced superior survival outcomes. The aim of this review was to perform a
      systematic review and meta-analysis to quantify the potential prognostic
      significance of positive seizure history in GBM patients. A search strategy was
      performed using the PRISMA guidelines for article identification, screening,
      eligibility and inclusion. Relevant articles were identified from six electronic
      databases from their inception to August 2017. These articles were screened
      against established criteria for inclusion into this study. Meta-analysis was
      conducted by pooling results with multivariate-adjusted hazard ratios (HRs).
      After screening, 6 relevant studies were included for analysis. There was a total
      cohort of 1836 GBM patients, of which 488 (27%) had a positive seizure history at
      initial presentation. There was a significant association found between positive
      seizure history in GBM patients and less mortality events, with an overall HR of
      0.71 (95%CI=0.63-0.81, p<0.00001, I2=4%). Positive seizure history at initial
      presentation of GBM can be associated with improved prognosis. However, there are
      a number of variables that need to be considered further, including genetic
      profiling, lead time bias, and anti-epileptic drug (AED) therapy. This review
      represents the highest level of evidence to date, and its result will be
      validated by future, prospective study of larger cohorts.

PMID- 29202378
TI  - Lacunar infarction in adult patients with moyamoya disease.
AB  - OBJECTIVES: Lacunar infarctions in moyamoya disease have rarely been described.
      We aimed to evaluate the features and prognosis of adult moyamoya patients with
      lacunar infarction. PATIENTS AND METHODS: We reviewed 696 consecutive moyamoya
      patients admitted to our hospital from 2009 to 2015 to identify patients with
      lacunar infarctions. We compared the clinical features and prognosis of adult
      moyamoya patients with lacunar infarction and those with non-lacunar infarction.
      Follow-up was conducted by face-to-face reviews or by a structured telephone
      interview. Outcome measures were recurrent stroke events and functional outcomes
      by modified Rankin Scale (mRS). RESULTS: We identified 32 patients with lacunar
      infarction among 197 adult moyamoya disease patients with infarctions. Patients
      with lacunar infarctions demonstrated similar angiographic features with patients
      with non-lacunar infarctions. During a mean follow-up of 33.02+/-20.49months, we
      observed recurrent stroke events in 1 patients with lacunar infarction and 14
      patients with non-lacunar infarction. The mean follow-up mRS was significantly
      better in the lacunar group than in the non-lacunar group (0.59+/-0.56 vs. 1.13+/
      1.24; P<0.001). CONCLUSION: We identified that the moyamoya patients with lacunar
      infarctions had better functional outcomes comparing with patients with non
      lacunar infarction after revascularization.

PMID- 29202379
TI  - Platelet monoamine oxidase activity and interpersonal violence in male suicide
      attempters.
AB  - Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central
      serotonergic functions, has been shown to correlate with criminal behavior in
      adolescents that come from an unfavorable psychosocial environment but not in
      adolescents from good conditions, indicating a link between environment, MAO-B
      activity and aggressive behavior. The purpose of this study was to examine the
      association between MAO-B activity and lifetime interpersonal violence in suicide
      attempters. The study included a total of 28 suicide attempters (18 men and 10
      women). Assessments of childhood exposure to and expressed interpersonal violence
      during childhood and as an adult were carried out with the Karolinska
      Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2
      phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations
      between platelet MAO-B activity and both exposure scores to interpersonal
      violence as a child and expressed lifetime interpersonal violence were
      significant in male suicide attempters (r = -0.61, p = 0.035; r = -0.84, p =
      0.0005), but not in women. Our finding of significant associations between
      interpersonal violence and low MAO-B activity need to be replicated in other
      cohorts of suicide attempters.

PMID- 29202380
TI  - Mortality, morbidity and medical resources utilization of patients with
      schizophrenia: A case-control community-based study.
AB  - Patients with schizophrenia have higher level of mortality and physical
      comorbidity compared to control population. However the association to primary-,
      secondary- and tertiary-medical resources utilization is not clear. We used a
      retrospective community-based cohort of patients with schizophrenia (n=1389; age
      37.53 years, 64.3% males) and, age-, gender-, and socioeconomic status-matched
      controls (n=4095; age 37.34 years; 64.3% males) who were followed-up for nine
      years. Mortality rate of patients was almost twice as high as that of matched
      controls (7% versus 3.8%). Diagnoses of ischemic heart disease and hypertension
      were more prevalent among controls than patients (8.2% versus 5%, and 21.6%
      versus 15.8%, respectively). Tertiary medical resources utilization was higher
      among patients with schizophrenia than control population (mean hospital
      admissions per year: 0.2 versus 0.12, emergency department visits: 0.48 versus
      0.36). Patients that died were more likely to have cardiovascular disease, to be
      admitted to general hospital and to spend more days in hospital than patients
      that did not die. There is a discrepancy between lower rates of cardiovascular
      disease diagnoses but higher rates of mortality and tertiary medical resources
      utilization among patients with schizophrenia when compared to control
      population. This may stem from an under-diagnosis and, eventually, under
      treatment of these patients.

PMID- 29202381
TI  - Set shifting and visuospatial organization deficits in body dysmorphic disorder.
AB  - Individuals with body dysmorphic disorder (BDD) over-attend to perceived
      defect(s) in their physical appearance, often becoming "stuck" obsessing about
      perceived flaws and engaging in rituals to hide flaws. These symptoms suggest
      that individuals with BDD may experience deficits in underlying neurocognitive
      functions, such as set-shifting and visuospatial organization. These deficits
      have been implicated as risk and maintenance factors in disorders with
      similarities to BDD but have been minimally investigated in BDD. The present
      study examined differences in neurocognitive functions among BDD participants (n
      = 20) compared to healthy controls (HCs; n = 20). Participants completed
      neuropsychological assessments measuring set-shifting (Cambridge
      Neuropsychological Test Automated Battery Intra-Extra Dimensional Set Shift [IED]
      task) and visuospatial organization and memory (Rey-Osterrieth Complex Figure
      Test [ROCF]). Results revealed a set-shifting deficit among BDD participants
      compared to HCs on the IED. On the ROCF, BDD participants exhibited deficits in
      visuospatial organization compared to HCs, but they did not differ in
      visuospatial memory compared to HCs. Results did not change when accounting for
      depression severity. Findings highlight neurocognitive deficits as potential
      endophenotype markers of clinical features (i.e., delusionality). Understanding
      neuropsychological deficits may clarify similarities and differences between BDD
      and related disorders and may guide targets for BDD treatment.

PMID- 29202382
TI  - Pesticide exposure, tobacco use, poor self-perceived health and presence of
      chronic disease are determinants of depressive symptoms among coffee growers from
      Southeast Brazil.
AB  - The lifestyle and other factors associated with the appearance of several health
      conditions that affect quality of life in rural zone is an issue that has been
      increasingly explored. Brazil is the largest coffee-producing nation in the world
      and has been a considerable consumer of pesticides since 2008. The aim of the
      present study was to investigate factors that could be contributing to the
      appearance of depressive symptoms in rural workers. Two hundred twenty male
      volunteers from nine cities in Southeast Brazil completed the Beck Depression
      Inventory-II (BDI-II) questionnaire about depressive symptoms and provided other
      information about socio-demographic characteristics and additional confounding
      factors. The adjusted multivariate logistic analysis demonstrated that pesticide
      exposure, tobacco use, poor self-perceived health and the presence of chronic
      disease contribute as risk factors for the appearance of depressive symptoms at a
      level above ups and downs considered normal in the BDI-II. This survey
      contributes to the search for solutions to improve quality of life and mental
      health in the rural living to the extent that social determinants of depression
      are being investigated.

PMID- 29202383
TI  - Correlation between interferon gamma and interleukin 6 with PTSD and resilience.
AB  - Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder with
      decreased general health prognosis and increased mortality. Inflammation has been
      hypothesised to be a link between PTSD and the most common co-morbid medical
      disorders. However, the relationship between inflammation and PTSD is not clear.
      Individual inflammatory markers have shown variable associations with PTSD. This
      study investigates the correlations between serum cytokines, PTSD and resilience
      in a cohort of Caucasian Vietnam combat veterans (n = 299). After correction for
      multiple testing, PTSD severity was correlated with small but significant
      decreases in interleukin 6 and interferon gamma (p = 0.004, p = 0.013,
      respectively) whereas resilience was correlated with increased levels of
      interleukin 6 and interferon gamma (p = 0.023; p = 0.007, respectively). Analyses
      of sub-symptoms of PTSD revealed that mood and arousal symptoms showed the most
      significant effect on interleukin 6 and interferon gamma. More research is needed
      to further elucidate the mechanisms underlying the relationship between cytokine
      levels, PTSD sub-symptoms and trauma outcomes to improve the knowledge base of
      differences in trauma response and the biological system.

PMID- 29202384
TI  - A comparison between the original and Tablet-based Symbol Digit Modalities Test
      in patients with schizophrenia: Test-retest agreement, random measurement error,
      practice effect, and ecological validity.
AB  - We aimed to compare the test-retest agreement, random measurement error, practice
      effect, and ecological validity of the original and Tablet-based Symbol Digit
      Modalities Test (T-SDMT) over five serial assessments, and to examine the
      concurrent validity of the T-SDMT in patients with schizophrenia. Sixty patients
      with chronic schizophrenia completed five serial assessments (one week apart) of
      the SDMT and T-SDMT and one assessment of the Activities of Daily Living Rating
      Scale III at the first time point. Both measures showed high test-retest
      agreement, similar levels of random measurement error over five serial
      assessments. Moreover, the practice effects of the two measures did not reach a
      plateau phase after five serial assessments in young and middle-aged
      participants. Nevertheless, only the practice effect of the T-SDMT became trivial
      after the first assessment. Like the SDMT, the T-SDMT had good ecological
      validity. The T-SDMT also had good concurrent validity with the SDMT. In
      addition, only the T-SDMT had discriminative validity to discriminate processing
      speed in young and middle-aged participants. Compared to the SDMT, the T-SDMT had
      overall slightly better psychometric properties, so it can be an alternative
      measure to the SDMT for assessing processing speed in patients with
      schizophrenia.

PMID- 29202385
TI  - Sensory over-responsivity in trichotillomania (hair-pulling disorder).
AB  - OBJECTIVE: This study was an initial investigation of sensory-over responsivity
      (SOR) to external sensations among individuals with trichotillomania (TTM).
      METHODS: Adults endorsing DSM-5 TTM criteria (N = 609) and a non-affected
      comparison sample (N = 268) completed a self-report survey. RESULTS: The majority
      of the TTM group endorsed SOR symptoms; three-quarters endorsed at least mild
      tactile and auditory SOR. About 15% endorsed SOR symptoms in the severe to
      extreme range. TTM participants had significantly higher mean scores in both
      auditory (t (652.89) = -6.51, p < .001, d = .45) and tactile (t (655.24) = -8.38,
      p < .001, d = .58) modalities than comparison participants, with medium effect
      sizes. Greater levels of SOR were related to greater levels of perfectionism and
      by-proxy pulling urges. SOR was significantly and positively correlated with
      functional impairment when controlling for TTM severity. CONCLUSION: This study
      expands prior work in obsessive-compulsive related disorders by contributing the
      first data about associations between TTM and over-responsivity to external
      sensations. Findings collectively suggest SOR may be related to maladaptive
      emotion regulation processes in TTM. A novel measure of SOR was developed and
      administered in this study.

PMID- 29202386
TI  - Vacuum FTIR study on the hygroscopicity of magnesium acetate aerosols.
AB  - Hygroscopicity and volatility of secondary organic aerosol (SOA) are two
      important properties, which determine the composition, concentration, size, phase
      state of SOA and thus chemical and optical properties for SOA. In this work,
      magnesium acetate (Mg(Ac)2) aerosol was used as a simple SOA model in order to
      reveal relationship between hygroscopicity and volatility. A novel approach was
      set up based on a combination of a vacuum FTIR spectrometer and a home-made
      relative humidity (RH) controlling system. The striking advantage of this
      approach was that the RH and the compositions of aerosols could be obtained from
      a same IR spectrum, which guaranteed the synchronism between RH and spectral
      features on a sub-second scale. At the constant RH of 90% and 80% for 3000s, the
      water content within Mg(Ac)2 aerosol particles decreased about 19.0% and 9.4%
      while there were 13.4% and 6.0% of acetate loss. This was attributed to a
      cooperation between volatile of acetic acid and Mg2+ hydrolysis in Mg(Ac)2
      aerosols, which greatly suppressed the hygroscopicity of Mg(Ac)2 aerosols. When
      the RH changed with pulsed mode between ~70% and ~90%, hygroscopicity relaxation
      was observed for Mg(Ac)2 aerosols. Diffuse coefficient of water in the relaxation
      process was estimated to be ~5*10-12m2.s-1 for the Mg(Ac)2 aerosols. Combining
      the IR spectra analysis, the decrease in the diffuse coefficient of water was due
      to the formation of magnesium hydroxide accompanying acetic acid evaporation in
      the aerosols.

PMID- 29202387
TI  - Successive ratio subtraction as a novel manipulation of ratio spectra for
      quantitative determination of a mixture of furosemide, spironolactone and
      canrenone.
AB  - Furosemide and spironolactone are commonly prescribed antihypertensive drugs.
      Canrenone is the main degradation product and main metabolite of spironolactone.
      Ratio subtraction and extended ratio subtraction spectrophotometric methods were
      previously applied for quantitation of only binary mixtures. An extension of the
      above mentioned methods; successive ratio subtraction, is introduced in the
      presented work for quantitative determination of ternary mixtures exemplified by
      furosemide, spironolactone and canrenone. Manipulating the ratio spectra of the
      ternary mixture allowed their determination at 273.6nm, 285nm and 240nm and in
      the concentration ranges of (2-16MUgmL-1), (4-32MUgmL-1) and (1-18MUgmL-1) for
      furosemide, spironolactone and canrenone, respectively. Method specificity was
      ensured by the application to laboratory prepared mixtures. The introduced method
      was ensured to be accurate and precise. Validation of the developed method was
      done with respect to ICH guidelines and its validity was further ensured by the
      application to the pharmaceutical formulation. Statistical comparison between the
      obtained results and those obtained from the reported HPLC method was achieved
      concerning student's t-test and F ratio test where no significant difference was
      observed.

PMID- 29202388
TI  - Comparison of three-way and four-way calibration for the real-time quantitative
      analysis of drug hydrolysis in complex dynamic samples by excitation-emission
      matrix fluorescence.
AB  - Multiway calibration in combination with spectroscopic technique is an attractive
      tool for online or real-time monitoring of target analyte(s) in complex samples.
      However, how to choose a suitable multiway calibration method for the resolution
      of spectroscopic-kinetic data is a troubling problem in practical application. In
      this work, for the first time, three-way and four-way fluorescence-kinetic data
      arrays were generated during the real-time monitoring of the hydrolysis of
      irinotecan (CPT-11) in human plasma by excitation-emission matrix fluorescence.
      Alternating normalization-weighted error (ANWE) and alternating penalty trilinear
      decomposition (APTLD) were used as three-way calibration for the decomposition of
      the three-way kinetic data array, whereas alternating weighted residual
      constraint quadrilinear decomposition (AWRCQLD) and alternating penalty
      quadrilinear decomposition (APQLD) were applied as four-way calibration to the
      four-way kinetic data array. The quantitative results of the two kinds of
      calibration models were fully compared from the perspective of predicted real
      time concentrations, spiked recoveries of initial concentration, and analytical
      figures of merit. The comparison study demonstrated that both three-way and four
      way calibration models could achieve real-time quantitative analysis of the
      hydrolysis of CPT-11 in human plasma under certain conditions. However, it was
      also found that both of them possess some critical advantages and shortcomings
      during the process of dynamic analysis. The conclusions obtained in this paper
      can provide some helpful guidance for the reasonable selection of multiway
      calibration models to achieve the real-time quantitative analysis of target
      analyte(s) in complex dynamic systems.

PMID- 29202389
TI  - EJC's biennial report on metastatic soft tissue sarcoma: State of the art and
      future perspectives.
AB  - In the last decade the limited treatment options for patients with metastatic
      soft tissue sarcoma have expanded considerably. With the addition of olaratumab
      to first-line treatment with doxorubicin, the introduction of several new agents
      in second-line treatment and beyond and other promising agents in the pipeline,
      perspectives of patients with metastatic soft tissue sarcoma are improving. Due
      to increasing insight into the biology of the different soft tissue sarcoma
      subtypes, choice of treatment has become much more histology-driven, although
      more prognostic and predictive factors are needed to further personalise therapy.
      This report summarises the current state of the art and discusses the promising
      developments in the treatment of patients with metastatic soft tissue sarcoma.

PMID- 29202390
TI  - Abnormal functional connectivity of high-frequency rhythms in drug-naive
      schizophrenia.
AB  - OBJECTIVE: The "dysconnection hypothesis" has been proposed as a core neural
      basis for schizophrenia. Although growing neuroimaging-based evidence suggests
      atypical functional connectivity in patients with schizophrenia, the results are
      inconsistent and the effects of antipsychotic treatment remain elusive. METHODS:
      We performed resting-state electroencephalography (EEG) in 21 drug-naive patients
      with schizophrenia (14 patients were re-evaluated after administration of
      antipsychotic treatment) and 31 age-matched healthy control subjects. We
      estimated functional connectivity, using the phase lag index (PLI), which
      captures the true synchronization of EEG signals. RESULTS: The patients had
      reduced functional connectivity of the beta band across frontal regions and of
      the gamma band throughout the scalp when compared to the control subjects. In the
      schizophrenia group, symptom severity did not seem associated with functional
      connectivity. Antipsychotic treatment led to no alterations in functional
      connectivity. CONCLUSIONS: Synchronous activity within and across brain areas
      over multiple frequencies reflect the integration of various types of information
      processing. Our findings of abnormal frequency- and region-specific functional
      connectivity patterns may provide further insight into the "dysconnection
      hypothesis" of schizophrenia. SIGNIFICANCE: The PLI may serve as a useful measure
      for the characterization and understanding of the intrinsic pathophysiological
      mechanisms of schizophrenia, and as a reliable biomarker for this disease.

PMID- 29202391
TI  - High-resolution ultrasound in patients with Wartenberg's migrant sensory
      neuritis, a case-control study.
AB  - OBJECTIVE: Wartenberg's migrant sensory neuritis (WMSN) is a rare, patchy, pure
      sensory neuropathy of unknown etiology. High-resolution ultrasonography (HRUS) is
      an emerging diagnostic technique for neuropathies, but it has not been applied in
      WMSN. In this study we aimed to determine HRUS abnormalities in WMSN. METHODS: We
      performed a case-control study of 8 newly diagnosed patients with WMSN and 22
      treatment-naive disease controls (16 patients with pure sensory axonal neuropathy
      and 6 with pure sensory chronic inflammatory demyelinating polyneuropathy (CIDP)
      or Lewis-Sumner syndrome (LSS)). All patients underwent routine diagnostic
      evaluations and a predefined HRUS protocol. RESULTS: We found multifocal nerve
      enlargement in all 8 WMSN patients. The median nerve in the upper arm and the
      sural nerve were significantly larger in WMSN than in axonal controls (p = 0.01
      and p = 0.04). In CIDP/LSS, sonographic enlargement was more extensive.
      Furthermore we found brachial plexus involvement in 3 of 8 (38%) WMSN patients.
      CONCLUSION: HRUS showed enlargement of multiple nerves in all WMSN patients even
      if clinical testing and NCS were normal. SIGNIFICANCE: The feature of multifocal
      nerve enlargement may be of additional value in establishing the diagnosis of
      WMSN and may support the suggestion of an auto-immune etiology.

PMID- 29202392
TI  - Serial hCG and progesterone levels to predict early pregnancy outcomes in
      pregnancies of uncertain viability: A prospective study.
AB  - OBJECTIVE: To assess the value of serial hCG and progesterone serum level in the
      diagnosis of early pregnancy viability. METHODS: It was a prospective cohort
      study. Women with a pregnancy of uncertain viability (PUV), defined as the
      presence of an intra-uterine embryo with a crown-rump length <7mm with no cardiac
      activity or an intra-uterine gestational sac size <25mm with no visible embryonic
      structure in a transvaginal ultrasound scan (TVS) were eligible. The diagnosis
      value of serial plasmatic hCG levels on the first day and 48h after as well as
      the initial progesterone level were evaluated to diagnose pregnancy viability.
      Pregnancy viability was assessed by TVS 7 to 14days after inclusion. RESULTS: The
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of an hCG H48/H0 ratio increase <11% to diagnose an early pregnancy
      loss were 70.6%, 100%, 100% and 85.3%, respectively. The sensitivity,
      specificity, PPV and NPV of a 6.2ng/ml progesterone level to diagnose an early
      pregnancy loss were 20%, 100%, 100% and 65.2%, respectively. The sensitivity,
      specificity, PPV and NPV of an hCG H48/H0 ratio increase >75% to diagnose a
      viable pregnancy were 100%, 31%, 45.9% and 100%, respectively. hCG H48/H0 ratio
      increase <11% was associated with early pregnancy loss in 100% of the cases. hCG
      H48/H0 ratio increase >75% was associated with 100% of viable pregnancies in 100%
      of the cases. CONCLUSION: Serial hCG levels alone permitted an early viability
      diagnosis within 48h for 41.1% of patients with PUV instead of 7 to 14days with
      TVS.

PMID- 29202393
TI  - Designing a lifestyle intervention to reduce risk of type 2 diabetes in
      postpartum mothers following gestational diabetes: An online survey with mothers
      and health professionals.
AB  - OBJECTIVE: The aim of this study was to identify what components of a postpartum
      lifestyle intervention would engage postpartum mothers who had a diagnosis of
      gestational diabetes. STUDY DESIGN: Two online surveys were conducted, one
      involving postnatal mothers with GDM (n=83), and a second for health
      professionals (n=46). RESULTS: Seventy-eight percent of mothers were aware that
      healthy eating, exercise and weight management were all important to reduce risk
      of subsequent type 2 diabetes. However, 80% of women in this survey were not
      ready to engage in a postpartum lifestyle intervention within the first 6 months
      of giving birth; in contrast 52% of health professionals recommended they should
      be engaged in the first six weeks. Group sessions were the most commonly chosen
      format to deliver an intervention (30%). A community setting was preferred to a
      medical one. Mothers wanted recipe ideas (95%) in preference to general dietary
      advice (76%) or cooking skills courses (39%). Walking was the main form of
      exercise for 79% of mothers in this sample. Women highlighted difficulty in
      focusing on their own health goals because of competing demands of looking after
      a baby (41% agreed, Median 3, IQR 2), tiredness (65% agreed, Md 4, IQR 1) and the
      need for childcare (64% agreed, Md 4, IQR 2). CONCLUSION: A walking programme,
      recipe ideas and weight monitoring may be useful components when designing a
      postpartum lifestyle intervention. Barriers to engagement are evident and the
      intervention should allow women to engage at a time that is appropriate for them.

PMID- 29202394
TI  - Common errors made in attempt to contract the pelvic floor muscles in women early
      after delivery: A prospective observational study.
AB  - OBJECTIVES: The ability to perform a correct pelvic floor muscle contraction
      (PFMC) is necessary to start pelvic floor muscle training after delivery. COMMOV
      are "c"ontractions of "o"ther "m"uscles (m. rectus abdominus, the gluteal
      muscles, and the adductors), and other "mov"ements (pelvic tilt, breath holding,
      and straining) performed in addition to or instead of the PFMC. COMMOV are
      probably the most common errors in attempt to contract the pelvic floor muscles
      during the first days after delivery. The aims of this study were to observe the
      prevalence of COMMOV, to investigate whether COMMOV influence the ability to
      perform a PFMC, and whether verbal instructions are effective to unlearn the
      COMMOV postpartum. STUDY DESIGN: A Prospective Observational Study was performed
      in women during the first through sixth day postpartum. PFMC and COMMOV were
      evaluated with visual observation. Women who did not show correct isolated PFMC
      received verbal instructions and were re-evaluated. Interobserver variability and
      agreement were calculated. Chi-square, Kappa, Risk Ratio, and McNemar were used.
      RESULTS: A total of 382 women participated, 2.36 (+/-1.2) days postpartum.
      Twohundred sixteen, 57%, CI (52-62%), showed COMMOV. The chance to perform a
      correct PFMC was 2.65 times higher without COMMOV (p=0.0001). Verbal feedback was
      effective (57% reduced to 3%) to abandon COMMOV during PFMC. CONCLUSION: COMMOV
      are common errors performed during attempts to contract the pelvic floor muscles
      after delivery. They can reduce the ability to contract the pelvic floor muscles,
      but can easily been unlearned with visual observation and verbal feedback.

PMID- 29202395
TI  - Generalized unprovoked vulvodynia; A retrospective study on the efficacy of
      treatment with amitriptyline, gabapentin or pregabalin.
AB  - OBJECTIVE: To describe patient characteristics of women diagnosed with
      generalized unprovoked vulvodynia (GUV) and to estimate efficacy and tolerability
      of treatment. MATERIAL AND METHODS: Retrospective observational study in 241
      women who presented with GUV at three vulvar disease clinics in Rotterdam, The
      Netherlands during 1996-2013. Main outcome was efficacy of amitriptyline,
      gabapentin or pregabalin treatment. RESULTS: The median duration of symptoms was
      24 months and median age 62 years (range 36-89). Most of the patients reported a
      burning sensation, often worsened by sitting, urinating or having intercourse.
      Treatment with either amitriptyline, gabapentin or pregabalin produced long
      lasting pain relief in 60% and temporary pain relief in 10%, while treatment was
      not successful in 30% of the patients. Around 30% of the patients had to stop
      their medication due to side effects. In 44 of the 241 (18%) women signs of
      vulvar dermatoses were present that could not explain the symptoms. These women
      experienced the same therapeutic efficacy as those without any visible
      abnormalities (chi-square goodness of fit p=0.49). CONCLUSIONS: Amitriptyline,
      gabapentin and pregabalin produced long lasting pain relief in most of the women
      with GUV. The 2015 International Society for the Study of Vulvovaginal Disease
      nomenclature acknowledges the concomitant presence of vulvar dermatoses and
      vulvodynia. This enables treatment of both conditions simultaneously, a situation
      that occurs regularly according to our study. We advocate that women with
      symptoms of GUV, with or without the presence of vulvar dermatoses, receive a
      therapeutic trial with drugs such as amitriptyline.

PMID- 29202396
TI  - Does coffee affect the bowel function after caesarean section?
AB  - OBJECTIVES: Postoperative ileus is a common consequence of abdominal surgery,
      which tends to prolong the duration of hospital stay and imposes considerable
      economic costs on healthcare system. Coffee is proved to have positive effects on
      gastrointestinal motility index in healthy young adults. Thus, the present study
      aims to examine effects of coffee on bowel function after caesarean section.
      MATERIAL AND METHOD: A total number 100 patients after elective caesarean section
      were randomly assigned before surgery into control and intervention groups. The
      intervention group received 100cc coffee at 8, 12 and 20h after the surgery,
      while the control group received 100cc hot water at the same intervals. First
      bowel sound, first passage of flatus, first defecation, and length of stay after
      surgery were compared in the two groups. FINDINGS: Mean time to first flatus
      passage was recorded in the control (22.54+/-5.09h) and intervention (17.28+/
      4.44h) groups and showed to be statistically significant (p=-0.000). However,
      average time of first defecation (intervention 37.22+/-16.31h; control 36.82+/
      16.5h; p=0.647) and mean time of hospital stay of patients (intervention 30.08+/
      9.50h; control 32.16+/-11.82h; p=0.518) and first bowel sound (intervention
      5.84+/-1.41h; control 6.16+/-1.33h; p=-0.326) were not statistically significant.
      DISCUSSION: Drinking coffee after a caesarean section reduces time to first
      flatus in patients. Nevertheless, further studies are needed to examine effects
      of coffee on ileus after elective caesarean section.

PMID- 29202397
TI  - Design, synthesis and biological evaluation of novel 2-aminobenzamides containing
      dithiocarbamate moiety as histone deacetylase inhibitors and potent antitumor
      agents.
AB  - A novel series of 2-aminobenzamides with dithiocarbamate as cap group were
      designed and synthesized as histone deacetylase (HDAC) inhibitors. Most newly
      synthesized compounds displayed potent antiproliferative activity against diverse
      human tumor cell lines. The most potent compounds, M101, M122 and M133 exhibited
      remarkably enhanced anticancer potency against 6 kinds of cancer cell lines with
      IC50 values of as low as 0.54-2.49 MUM compared with CS055 (2.28~ >26 MUM) and
      MS275 (0.47-6.74 MUM). HDAC isoform selectivity assay indicated that M101, M122
      and M133 are HDAC1 and HDAC2 selective inhibitors. We also rationalize the high
      potency and selectivity of compound M122 by molecular docking. Further
      investigation showed that M101, M122 and M133 could inhibit colony formation of
      human hepatocellular carcinoma cell line SMMC7721. Furthermore, M101, M122 and
      M133 remarkably induced apoptosis in SMMC7721 cancer cells. M101 and M133 were
      found to potently induce SMMC7721 cancer cell cycle arrest at G2/M phase. This
      study demonstrated that introducing dithiocarbamate as the capping group of 2
      aminobenzamide is effective for improving both HDAC inhibitory activity and
      antitumor activity. The most potent compounds, M101, M122 and M133 could be
      promising candidates for cancer therapy.

PMID- 29202398
TI  - Synthesis and biological characterization of ubenimex-fluorouracil conjugates for
      anti-cancer therapy.
AB  - Previously a novel ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified
      and validated as a potent CD13 inhibitor with marked in vitro and in vivo
      antitumor potency. Herein, further structural modifications of the linker part of
      BC-01 was carried out to get more potent and stable ubenimex-fluorouracil
      conjugates. It was striking that most of these conjugates showed even more potent
      CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor ubenimex.
      One representative compound 12a displayed significant in vitro anti
      proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13+ cell
      elimination effects. In vitro stability and in vivo pharmacokinetic study
      revealed that compound 12a could release ubenimex and 5-FU slowly, which could
      act as a mutual prodrug of ubenimex and 5-FU. Compared with 5-FU or 5-FU plus
      ubenimex, 12a exhibited superior in vivo antitumor growth efficiency, even in our
      mice model of 5-FU-resistant liver cancer. Moreover, 12a exhibited more potent in
      vivo anti-metastasis and lifespan extension effects compared to the approved 5-FU
      prodrug capecitabine. Collectively, these results suggest that further
      optimization and evaluation of 12a as a promising anticancer candidate are
      warranted to develop effective therapeutic agents for human liver cancer.

PMID- 29202399
TI  - Urokinase receptor derived peptides as potent inhibitors of the formyl peptide
      receptor type 1-triggered cell migration.
AB  - The receptor for the urokinase-type plasminogen activator (uPAR) is a widely
      recognized master regulator of cell migration. We and others have previously
      documented that the uPAR(84-95) sequence, interacts with the formyl peptide
      receptors (FPR)s, henceforth inducing cell migration of several cell lines,
      including leukocytes, and the synthetic shorter peptide (Ser88-Arg-Ser-Arg-Tyr92,
      SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have
      developed the head-to-tail cyclic analog [SRSRY], a new potent and stable
      inhibitor of monocyte trafficking. This prompted us to develop novel cyclic and
      linear analogs of [SRSRY] with the aim to broaden the knowledge about structure
      activity relationships of peptide [SRSRY]. Herein we report their synthesis,
      effects on cell migration, conformational and docking analyses which served to
      envisage a new pharmacophore model for inhibitors of FPR1-triggered cell
      migration.

PMID- 29202400
TI  - Discovery of caffeic acid phenethyl ester derivatives as novel myeloid
      differentiation protein 2 inhibitors for treatment of acute lung injury.
AB  - Myeloid differentiation protein 2 (MD2) is an essential molecule which recognizes
      lipopolysaccharide (LPS), leading to initiation of inflammation through the
      activation of Toll-like receptor 4 (TLR4) signaling. Caffeic acid phenethyl ester
      (CAPE) from propolis of honeybee hives could interfere interactions between LPS
      and the TLR4/MD2 complex, and thereby has promising anti-inflammatory properties.
      In this study, we designed and synthesized 48 CAPE derivatives and evaluated
      their anti-inflammatory activities in mouse primary peritoneal macrophages (MPMs)
      activated by LPS. The most active compound, 10s, was found to bind with MD2 with
      high affinity, which prevented formation of the LPS/MD2/TLR4 complex. The binding
      mode of 10s revealed that the major interactions with MD2 were established via
      two key hydrogen bonds and hydrophobic interactions. Furthermore, 10s showed
      remarkable protective effects against LPS-caused ALI (acute lung injury) in vivo.
      Taken together, this work provides new lead structures and candidates as MD2
      inhibitors for the development of anti-inflammatory drugs.

PMID- 29202401
TI  - Synthesis, biological evaluation and structure-activity relationship studies of
      hederacolchiside E and its derivatives as potential anti-Alzheimer agents.
AB  - Inspired by the previously reported neuroprotective activity of hederacolchiside
      E (1), we synthesized hederacolchiside E for the first time along with eleven of
      its derivatives. The neuroprotective effects of these compounds were further
      evaluated against H2O2- and Abeta1-42-induced injury using cell-based assays. The
      derivatives showed obvious differences in activity due to structural variations,
      and two of them exhibited better neuroprotective effects than 1 in the Abeta1-42
      induced injury model. Compound 7 was the most active derivative and had a
      relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce
      the release of lactate dehydrogenase (LDH), level of intracellular reactive
      oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from
      Abeta1-42 treatment, which demonstrated that these kinds of compounds show
      neuroprotective effects in Alzheimer's disease (AD) models via modulating
      oxidative stress. Compound 7 could be used as promising lead for the development
      of a new type of neuroprotective agent against AD.

PMID- 29202402
TI  - Design, synthesis, and biological evaluation of a series of resorcinol-based N
      benzyl benzamide derivatives as potent Hsp90 inhibitors.
AB  - Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is
      responsible for the stabilization and maturation of many oncogenic proteins.
      Therefore, Hsp90 has emerged as an attractive target in the field of cancer
      chemotherapy. In this study, we report the design, synthesis, and biological
      evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a
      significant Hsp90alpha inhibitory activity with IC50 value of 5.3 nM and an
      excellent growth inhibition with GI50 value of 0.42 MUM against non-small cell
      lung cancer cells, H1975. Compound 30f effectively reduces the expression levels
      of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently,
      compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8,
      indicating that 30f induces cancer cell death via apoptotic pathway. Moreover,
      cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on
      the activities of five major P450 isoforms (IC50 > 5 MUM for 1A2, 2C9, 2C19, 2D6,
      and 3A), suggesting that clinical interactions between 30f and the substrate
      drugs of the five major P450 isoforms are not expected. Compound 30f also
      inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975
      without noticeable abnormal behavior and body weight changes. The immunostaining
      and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of
      tumor further demonstrate a good agreement with the in vitro results.

PMID- 29202403
TI  - Design, synthesis and structure-activity relationship of a focused library of
      beta-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing
      mechanisms in breast cancer.
AB  - Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmudulin-dependent
      protein kinase, belonging to a small family of an atypical Ser/Thr-protein
      kinase. eEF2K has been recently reported to be highly activated or overexpressed
      in many types of cancer; therefore, eEF2K would be regarded as a promising
      therapeutic target. In this study, we discovered a beta-phenylalanine scaffold by
      virtual high-throughput screening, as well as designed and synthesized 46
      derivatives with assessment of inhibition activity against eEF2K and
      cytotoxicity. After several rounds of kinase and anti-proliferative activity
      screening, we discovered an eEF2K inhibitor (21l) with best eEF2K enzymatic
      activity (IC50 of 5.5 MUM) and anti-proliferative activity (MDA-MB-231 cells,
      IC50 of 12.6 MUM, MDA-MB-436 cells, IC50 of 19.8 MUM). Moreover, we found that
      21l could induce cell death via the apoptotic pathways in MDA-MB-231 and MDA-MB
      436 cells. Subsequently, we evaluated its anti-tumor activity and apoptosis
      inducing mechanisms in vivo. These results suggested that 21l inhibited tumor
      growth by apoptosis in the xenograft mouse model of breast cancer (MDA-MB-231 and
      MDA-MB-436). Collectively, our results demonstrate a novel small-molecule
      inhibitor targeting eEF2K with mechanism of apoptosis and a therapeutic potential
      in breast cancer.

PMID- 29202404
TI  - Discovery of a novel series of alpha-terpineol derivatives as promising anti
      asthmatic agents: Their design, synthesis, and biological evaluation.
AB  - A series of novel alpha-terpineol derivatives were designed and synthesized
      through structural derivatization of the tertiary hydroxyl moiety or reduction of
      the double bond. Of the resulting compounds, eight compounds enhanced relaxation
      of airway smooth muscle (ASM) compared to the alpha-terpineol precursor, and four
      compounds (4a, 4d, 4e, and 4i)were superior or comparable to aminophylline at a
      concentration of 0.75 mmol/L. Assays for 3'-5'-Cyclic adenosine monophpsphate
      (cAMP) activation revealed that some representative alpha-terpineol derivatives
      in this series were capable of upregulating the level of cAMP in ASM cells.
      Further in vivo investigation using the asthmatic rat model, illustrated that
      treatment with the compounds 4a and 4e resulted in significantly lowered lung
      resistance (RL) and enhanced dynamic lung compliance (Cldyn), two important
      parameters for lung fuction. Moreover, treatment with 4e downregulated the levels
      of both IL-4 and IL-17. Due to its several favorable physiological functions,
      including ASM relaxation activity, cAMP activation capability, and in vivo anti
      asthmatic efficacy, 4e is a promising remedy for bronchial asthma, meriting
      extensive development.

PMID- 29202405
TI  - Potent aromatase inhibitors and molecular mechanism of inhibitory action.
AB  - Estrogen is a significant factor in the maintenance and progression of hormone
      dependent breast cancer. As well known, aromatase mediates the production of
      estrogen. Thus, inhibition of aromatase with chemical molecules has been
      considered to be an effective treatment for estrogen receptor-positive (ER+)
      breast cancer. In this work, we designed and synthesized a series of novel non
      steroidal molecules containing 2-phenylindole scaffold and moiety of either
      imidazole or 1,2,4-triazole to enhance their binding capacity with the aromatase.
      Among these molecules, a compound named as 8o was confirmed experimentally to
      have the highest inhibitory activity to aromatase. Further cell activity assay
      proved that compound 8o has low cytotoxicity and is a promising lead for
      developing novel aromatase inhibitors. Molecular modeling and simulation
      techniques were performed to identify the binding modes of letrozole and 8o with
      the aromatase. Analysis of energy of the two compound-aromatase complexes
      revealed that the 8o has low binding energy (strong binding affinity) to the
      aromatase as compared to letrozole, which was in accordance with the experimental
      results. As concluded, a combination of experimental and computational approaches
      facilitates us to understand the molecular mechanism of inhibitory action and
      discover more potent non-steroidal AIs against aromatase, thereby opening up a
      novel therapeutic strategy for hormone-dependent breast cancer.

PMID- 29202406
TI  - Pyrano[3,2-a]carbazole alkaloids as effective agents against ischemic stroke in
      vitro and in vivo.
AB  - A series of pyrano[3,2-a]carbazole alkaloids were designed and synthesized as
      analogues of Claulansine F (Clau F, 10a) isolated from Clausena lansium. Some of
      compounds showed strong neuroprotective effects and were promising agents against
      ischemic stroke. Among these compounds, 7c was the most active in inhibiting the
      programmed death of PC12 cells and primary cortical neurons. This compound
      induced neuroprotection following ischemic reperfusion and decreased neurological
      deficit scores in treated animals. Furthermore, 7c could penetrate the blood
      brain barrier (BBB) in rats, and its exposure in the brain was 4.3-fold higher
      than that in plasma. More importantly, compared to edaravone, 7c exhibited
      stronger free radical scavenging activity. Our findings suggest that 7c may be
      promising for further evaluation as an intervention for ischemic stroke.

PMID- 29202407
TI  - Exploiting polypharmacology for improving therapeutic outcome of kinase
      inhibitors (KIs): An update of recent medicinal chemistry efforts.
AB  - Polypharmacology has been increasingly advocated for the therapeutic intervention
      in complex pathological conditions, exemplified by cancer. Although kinase
      inhibitors (KIs) have revolutionized the treatment for certain types of
      malignancies, some major medical needs remain unmet due to the relentless advance
      of drug resistance and insufficient efficacy of mono-target KIs. Hence, "multiple
      targets, multi-dimensional activities" represents an emerging paradigm for
      innovative anti-cancer drug discovery. Over recent years, considerable leaps have
      been made in pursuit of kinase-centric polypharmacological anti-cancer
      therapeutics, providing avenues to tackling the limitation of mono-target KIs. In
      the review, we summarize the clinically important mechanisms inducing KI
      resistance and depict a landscape of recent medicinal chemistry efforts on
      exploring kinase-centric polypharmacological anti-cancer agents that targeting
      multiple cancer-related processes. In parallel, some inevitable challenges are
      emphasized for the sake of more accurate and efficient drug discovery in the
      field.

PMID- 29202408
TI  - Synthesis and antimycobacterial activity of triterpeni? A-ring azepanes.
AB  - A series of A-ring azepanones and azepanes derived from betulonic, oleanonic and
      ursonic acids was synthesized and evaluated for their in vitro antimycobacterial
      activities against M. tuberculosis (MTB) H37Rv and SDR-TB in the National
      Institute of Allergy and Infectious Diseases. Triterpenic A-azepano-28-hydroxy
      derivatives were synthesized by the reduction with LiAlH4 of triterpenic
      azepanones available from the Beckmann rearrangement of the corresponding C3
      oximes. Modification of azepanes at NH-group and atoms S12, C20, C28 and C29 of
      triterpenic core led to the derivatives with oxo, epoxy, aminopropyl, oximino and
      acyl substituents. The primary assay of tested triterpenoids against MTB H37Rv
      demonstrated their MIC values ranged from 3.125 to >200 MUM. Ursane type A
      azepano-28-cinnamoates were the most active being 2 and 4 times more efficient
      than the initial 28-hydroxy-derivative. The follow-up testing revealed A-azepano
      28-cinnamoyloxybetulin as a leader compound with MIC 2 and MBC 4 MUM against MTB
      H37Rv and MICs 4, 1 and 1 MUM against INH, RIF and OFX resistant strains,
      respectively. Five oleanane and ursane azepanes pronounced better activity than
      isoniazid against INH-R1 and rifampicin against INH-R2 strains. This work opens a
      new direction in the design and synthesis of new antitubercular agents basing on
      azepanotriterpenoids.

PMID- 29202409
TI  - A fluorine scan of a tubulin polymerization inhibitor isocombretastatin A-4:
      Design, synthesis, molecular modelling, and biological evaluation.
AB  - A novel series of tubulin polymerization inhibitors, based on fluorinated
      derivatives of isocombretastatin A-4 was synthesized with the goal of evaluating
      the effect of these compounds on the proliferative activity. The introduction of
      fluorine atom was performed on the phenyl ring or at the linker between the two
      aromatic rings. The modification of isoCA-4 by introduction of difluoromethoxy
      group at the para-position (3i) and substitution of the two protons of the linker
      by two fluorine atoms (3m), produced the most active compounds in the series,
      with IC50 values of 0.15-2.2 nM (3i) and 0.1-2 nM (3m) respectively, against a
      panel of six cancer cell lines. Compounds 3i and 3m had greater antiproliferative
      activity in comparison with references CA-4 or isoCA-4, the presence of fluorine
      group leads to a significant enhancement of the antiproliferative activity.
      Molecular docking studies indicated that compounds 3i and 3m occupy the
      colchicine binding site of tubulin. Evaluation of cytotoxicity in Human noncancer
      cells indicated that the compounds 3i and 3m were practically ineffective in
      quiescent peripheral blood lymphocytes, and may have a selective
      antiproliferative activity against cancer cells. Analyses of cell cycle
      distribution, and morphological microtubules organization showed that compound 3m
      induced G2/M phase arrest and, dramatically disrupted the microtubule network.

PMID- 29202410
TI  - Discovery, optimization and biological evaluation for novel c-Met kinase
      inhibitors.
AB  - The c-Met kinase has emerged as an attractive target for developing antitumor
      agents because of its close relationship with the development of many human
      cancers, poor clinical outcomes and even drug resistance. A series of novel c-Met
      kinase inhibitors have been identified with multiple workflow in this work,
      including virtual screening, X-ray crystallography, biological evaluation and
      structural optimization. The experimentally determined crystal structure of the
      best hit compound HL-11 in c-Met kinase domain was highly consistent with the
      computational prediction. Comparison of the hit compounds with different c-Met
      kinase inhibitory activity by molecular dynamics simulations suggested the key
      protein-ligand interactions for structural optimization. Based on these,
      structural optimization produced compound 11e with better c-Met kinase inhibitory
      activity and improved anti-proliferative activity. These experimental findings
      proved the reliability and efficiency of our in silico methods. This strategy
      will facilitate further lead discovery and optimization for novel c-Met kinase
      inhibitors.

PMID- 29202411
TI  - Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine
      perfluorinated ligand shows strong activity towards colorectal cancer cells.
AB  - Three new compounds have been synthesized and completely characterized by
      analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand
      L1 and the new organometallic complex [Ru(eta5-MeCp)(PPh3)2Cl] (Ru1) crystalize
      in the centrosymmetric triclinic space group P1-. Analysis of the phenotypic
      effects induced by both organometallic complexes Ru1 and [Ru(eta5
      MeCp)(PPh3)(L1)][CF3SO3] (Ru2), on human colorectal cancer cells (SW480 and RKO)
      survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times
      higher than cisplatin, and induce apoptosis in these cells. Data obtained in a
      noncancerous cell line derived from normal colon epithelial cells (NCM460)
      revealed an intrinsic selectivity of Ru2 for malignant cells at low
      concentrations, showing the high potential of this compound as a selective
      anticancer agent.

PMID- 29202413
TI  - Alteration of host-pathogen interactions in the wake of climate change -
      Increasing risk for shellfish associated infections?
AB  - The potential for climate-related spread of infectious diseases through marine
      systems has been highlighted in several reports. With this review we want to draw
      attention to less recognized mechanisms behind vector-borne transmission pathways
      to humans. We have focused on how the immune systems of edible marine shellfish,
      the blue mussels and Norway lobsters, are affected by climate related
      environmental stressors. Future ocean acidification (OA) and warming due to
      climate change constitute a gradually increasing persistent stress with negative
      trade-off for many organisms. In addition, the stress of recurrent hypoxia,
      inducing high levels of bioavailable manganese (Mn) is likely to increase in line
      with climate change. We summarized that OA, hypoxia and elevated levels of Mn did
      have an overall negative effect on immunity, in some cases also with synergistic
      effects. On the other hand, moderate increase in temperature seems to have a
      stimulating effect on antimicrobial activity and may in a future warming scenario
      counteract the negative effects. However, rising sea surface temperature and
      climate events causing high land run-off promote the abundance of naturally
      occurring pathogenic Vibrio and will in addition, bring enteric pathogens which
      are circulating in society into coastal waters. Moreover, the observed
      impairments of the immune defense enhance the persistence and occurrence of
      pathogens in shellfish. This may increase the risk for direct transmission of
      pathogens to consumers. It is thus essential that in the wake of climate change,
      sanitary control of coastal waters and seafood must recognize and adapt to the
      expected alteration of host-pathogen interactions.

PMID- 29202412
TI  - Treatment of swine wastewater in continuous activated sludge systems under
      different dissolved oxygen conditions: Reactor operation and evaluation using
      modelling.
AB  - Swine wastewater was treated in two continuously aerated activated sludge (AS)
      systems at high (AS1: 1.7-2.6 mg/L) and low (AS2: 0.04-0.08 mg/L) dissolved
      oxygen (DO), and at three temperatures (10, 20, and 30  degrees C). Biochemical
      oxygen demand (BOD) removal was >94.8%. Meanwhile, total nitrogen (N) removal was
      significantly higher in AS2, at 64, 89, and 88%, than in AS1, at 12, 24, and 46%,
      for 10, 20, and 30  degrees C, respectively. The experimental data were
      considered in a simulation study using an AS model for BOD and N removal, which
      also included nitrite, free ammonia, free nitrous acid, and temperature.
      Simulations at high-DO showed that ammonium was partly oxidized into nitrate but
      not removed, whereas at low-DO ammonium was removed mainly through the nitrite
      shortcut in simultaneous nitrification-denitrification. This study demonstrates
      that treatment at low-DO is an effective method for removing N, and modelling a
      helpful tool for its optimization.

PMID- 29202414
TI  - Study on the tribological behavior of surgical suture interacting with a skin
      substitute by using a penetration friction apparatus.
AB  - Surgical sutures have different sizes, structures, whereas they are being used
      for various surgeries. The high friction performance of surgical sutures in the
      suturing process may cause inflammation and pain, leading to a longer recovery
      time. This paper presents an understanding of the tribological behavior of
      surgical suture with monofilament and multifilament structures, by means of a
      penetration friction apparatus (PFA). The results indicated that structure and
      surface topography of the surgical suture had a pronounced effect on the
      tribological interactions. It was found that the friction force and abrasion area
      of skin substitute with the penetration of polyglycolic acid (PGA) multifilament
      surgical suture were larger than that of Nylon monofilament surgical suture.
      Meanwhile, more abrasion at the pull-in boundary of skin substitute was observed
      compared with that at the pull-out boundary.

PMID- 29202415
TI  - The interplay between viperin antiviral activity, lipid droplets and Junin
      mammarenavirus multiplication.
AB  - Junin arenavirus infections are associated with high levels of interferons in
      both severe and fatal cases. Upon Junin virus (JUNV) infection a cell signaling
      cascade initiates, that ultimately attempts to limit viral replication and
      prevent infection progression through the expression of host antiviral proteins.
      The interferon stimulated gene (ISG) viperin has drawn our attention as it has
      been highlighted as an important antiviral protein against several viral
      infections. The studies of the mechanistic actions of viperin have described
      important functional domains relating its antiviral and immune-modulating actions
      through cellular lipid structures. In line with this, through silencing and
      overexpression approaches, we have identified viperin as an antiviral ISG against
      JUNV. In addition, we found that lipid droplet structures are modulated during
      JUNV infection, suggesting its relevance for proper virus multiplication.
      Furthermore, our confocal microscopy images, bioinformatics and functional
      results also revealed viperin-JUNV protein interactions that might be
      participating in this antiviral pathway at lipid droplet level. Altogether, these
      results will help to better understand the factors mediating innate immunity in
      arenavirus infection and may lead to the development of pharmacological agents
      that can boost their effectiveness thereby leading to new treatments for this
      viral disease.

PMID- 29202416
TI  - Evaluation of the toxic response induced by azoxystrobin in the non-target green
      alga Chlorella pyrenoidosa.
AB  - The top-selling strobilurin, azoxystrobin (AZ), is a broad-spectrum fungicide
      that protects against many kinds of pathogenic fungi by preventing their ATP
      production. The extensive use of AZ can have negative consequences on non-target
      species and its effects and toxic mechanisms on algae are still poorly
      understood. In this work, Chlorella pyrenoidosa that had been grown in BG-11
      medium was exposed to AZ (0.5-10 mg L-1) for 10 d. The physiological and
      molecular responses of the algae to AZ treatment, including photosynthetic
      efficiency, lipid peroxidation level, antioxidant enzyme activities, as well as
      transcriptome-based analysis of gene expression, were examined to investigate the
      potential toxic mechanism. Results shows that the photosynthetic pigment (per
      cell) increased slightly after AZ treatments, indicating that the photosystem of
      C. pyrenoidosa may have been strengthened. Glutathione and ascorbate contents
      were increased, and antioxidant enzyme activities were induced to relieve
      oxidative damage (e.g., from lipid peroxidation) in algae after AZ treatment.
      Transcriptome-based analysis of gene expression combined with physiological
      verification suggested that the 5 mg L-1 AZ treatment did not inhibit ATP
      generation in C. pyrenoidosa, but did significantly alter amino acid metabolism,
      especially in aspartate- and glutamine-related reactions. Moreover, perturbation
      of ascorbate synthesis, fat acid metabolism, and RNA translation was also
      observed, suggesting that AZ inhibits algal cell growth through multiple
      pathways. The identification of AZ-responsive genes in the eukaryotic alga C.
      pyrenoidosa provides new insight into AZ stress responses in a non-target
      organism.

PMID- 29202417
TI  - Metabolism of tri-n-butyl phosphate in earthworm Perionyx excavatus.
AB  - Tri-n-butyl phosphate (TBP) is widely used in various industrial processes and
      has been detected in all environmental matrices. So far, little work has been
      done regarding the metabolism of TBP on terrestrial invertebrates. We
      investigated the metabolism of TBP in the earthworm, Perionyx excavatus, after
      acute exposure to TBP for one and two days in filter paper contact test, as well
      as after chronic exposure for 28 days in soil experiment. Biotransformation
      products were identified by using liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometry, and by exploiting the information dependent
      acquisition in tandem mass spectrometry. TBP exhibited low accumulation in
      earthworm-soil ecosystem at 10 mg/kg and 50 mg/kg. The presence of earthworms
      significantly enhanced TBP degradation at 50 mg/kg in soil. Dibutyl phosphate and
      hydroxylated TBP were the major phase I metabolites. Three novel phase II
      metabolites were identified: ethanol dibutyl phosphate and its sulfate conjugate,
      and the phosphate conjugate of hydroxylated TBP. Hydroxylation and further
      phosphorylation dominated metabolism in chronic exposure. An extensive metabolic
      pathway of TBP in earthworm was proposed. This is the first report of TBP
      metabolism in terrestrial invertebrates and highlights the necessity to identify
      metabolites of contaminants when evaluating their bioaccumulation and toxicity.

PMID- 29202418
TI  - Prenatal urinary polycyclic aromatic hydrocarbon metabolites, global DNA
      methylation in cord blood, and birth outcomes: A cohort study in China.
AB  - BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a
      potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play
      a key role in which PAHs exert its effects. OBJECTIVE: Our study aimed to examine
      whether prenatal PAH exposure was associated with adverse birth outcomes and
      altered DNA methylation and to explore potential mediating roles of DNA
      methylation. METHODS: Ten urinary PAH metabolites were measured from 106 pregnant
      women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation
      in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as
      surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing.
      Multivariable linear regression was used to estimate the associations of urinary
      PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis
      was also conducted. RESULTS: Prenatal urinary 2-hydroxynaphthalene (2-OHNa),
      ?OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (?OH-PAHs) were
      associated with lower birth length (e.g., -0.80%, 95% CI: -1.39%, -0.20% for the
      third vs. first tertile of 2-OHNa; p for trend = 0.01). Prenatal urinary 2-OHNa
      and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1
      methylation (e.g., -1.88%, 95% CI: -3.73%, -0.10% for the third vs. first tertile
      tertile of 2-OHNa in Alu methylation; p for trend = 0.04). Mediation analysis
      failed to show a mediator effect of global DNA methylation in the association
      between prenatal urinary OH-PAHs and birth outcomes. CONCLUSIONS: Prenatal
      specific PAH exposures are associated with decreased birth length and global DNA
      methylation. However, global DNA methylation does not mediate the associations of
      prenatal PAH exposure with birth outcomes. Further studies are needed to confirm
      the results.

PMID- 29202419
TI  - Ultrafine particulate matter impairs mitochondrial redox homeostasis and
      activates phosphatidylinositol 3-kinase mediated DNA damage responses in
      lymphocytes.
AB  - Particulate matter (PM), broadly defined as coarse (2.5-10 MUm), fine (0.1-2.5
      MUm) and ultrafine particles (<=0.1 MUm), is a major constituent of ambient air
      pollution. Recent studies have linked PM exposure (coarse and fine particles)
      with several human diseases including cancer. However, the molecular mechanisms
      underlying ultrafine PM exposure induced cellular and sub-cellular repercussions
      are ill-defined. Since mitochondria are one of the major targets of different
      environmental pollutants, we herein aimed to understand the molecular
      repercussion of ultrafine PM exposure on mitochondrial machinery in peripheral
      blood lymphocytes. Upon comparative analysis, a significantly higher DCF
      fluorescence was observed in ultrafine PM exposed cells that confirmed the strong
      pro-oxidant nature of these particles. In addition, the depleted activity of
      antioxidant enzymes, glutathione reductase and superoxide dismutase suggested the
      strong association of ultrafine PM with oxidative stress. These results further
      coincided with mitochondrial membrane depolarization, altered mitochondrial
      respiratory chain enzyme activity and decline in mtDNA copy number. Moreover, the
      higher accumulation of DNA damage response proteins (gammaH2AX, pATM, p-p53),
      suggested that exposure to ultrafine PM induces DNA damage and triggers
      phosphatidylinositol 3 kinase mediated response pathway. Further, the alterations
      in mitochondrial machinery and redox balance among ultrafine PM exposed cells
      were accompanied by a considerably elevated pro-inflammatory cytokine response.
      Interestingly, the lower apoptosis levels observed in ultrafine particle treated
      cells suggest the possibility that the marked alterations may lead to the
      impairment of mitochondrial-nuclear cross talk. Together, our results showed that
      ultrafine PM, because of their smaller size possesses significant ability to
      disturb mitochondrial redox homeostasis and activates phosphatidylinositol 3
      kinase mediated DNA damage response pathway, an unknown molecular paradigm of
      ultrafine PM exposure. Our findings also indicate that maneuvering through the
      mitochondrial function might be a viable, indirect method to modulate lymphocyte
      homeostasis in air pollution associated immune disorders.

PMID- 29202420
TI  - Detecting sulfamethoxazole and carbamazepine in groundwater: Is ELISA a reliable
      screening tool?
AB  - In recent years, numerous studies have reported the prevalence of organic
      micropollutants in natural waters. There is an increasing interest in assessing
      the occurrence and transport of these contaminants in groundwater because a large
      number of people in the United States rely on groundwater for their drinking
      water. However, commonly used mass-spectrometry-based analytical methods are
      expensive and time-consuming. The enzyme-linked immunosorbent assay (ELISA)
      method offers an inexpensive analytical alternative that provides semi
      quantitative results in a relatively quick timeframe. We investigated the use of
      ELISA for two commonly detected micropollutants, sulfamethoxazole (SMX) and
      carbamazepine (CBZ), in groundwater collected as part of two different studies,
      one in Minnesota and the other in Iowa. The ELISA results were compared with two
      mass-spectrometry-based methods: (1) direct aqueous injection-high performance
      liquid chromatography/tandem mass spectrometry (HPLC) and (2) online solid-phase
      extraction with liquid chromatography/electrospray ionization-mass spectrometry
      (SPE LC). Differences in SMX and CBZ observations between ELISA and both HPLC and
      SPE LC were analyzed using the Paired Prentice-Wilcoxon test. Estimates of bias
      and limits of agreement between paired observations also were calculated. The SMX
      determinations by ELISA yielded results that were 30 and 14% greater than HPLC
      and SPE LC, respectively. The CBZ determinations by ELISA yielded results that
      were 25 and 9% greater than HPLC and SPE LC, respectively. The ELISA
      determinations were in presence-absence agreement with HPLC for 83% of samples
      for SMX and CBZ; and with SPE LC for 76 and 80% of samples for SMX and CBZ,
      respectively. Results indicate that ELISA for SMX and CBZ is a reliable and cost
      effective screening-tool alternative to more commonly used mass spectrometry
      based analytical methods.

PMID- 29202421
TI  - Impacts of sea-land and mountain-valley circulations on the air pollution in
      Beijing-Tianjin-Hebei (BTH): A case study.
AB  - In the study, observational data analyses and the WRF-CHEM model simulations are
      used to investigate the role of sea-land and mountain-valley breeze circulations
      in a severe air pollution event occurred in Beijing-Tianjin-Hebei (BTH) during
      August 9-10, 2013. Both the wind observations and the model simulations have
      clearly indicated the evolution of the sea-land and mountain-valley breeze
      circulations during the event. The WRF-CHEM model generally reproduces the local
      meteorological circulations and also performs well in simulating temporal
      variations and spatial distributions of fine particulate matters (PM2.5) and
      ozone (O3) concentrations compared to observations in BTH. The model results have
      shown that the offshore land breeze transports the pollutants formed in Shandong
      province to the Bohai Gulf in the morning, causing the formation of high O3 and
      PM2.5 concentrations over the gulf. The onshore sea breeze not only causes the
      formation of a convergence zone to induce upward movement, mitigating the surface
      pollution to some degree, also recirculates the pollutants over the gulf to
      deteriorate the air quality in the coastal area. The upward valley breeze brings
      the pollutants in the urban area of Beijing to the mountain area in the
      afternoon, and the downward mountain breeze transports the pollutants back during
      nighttime. The intensity of the mountain-valley breeze circulation is weak
      compared to the land-sea breeze circulation in BTH. It is worth noting that the
      local circulations play an important role when the large-scale meteorological
      conditions are relatively weak.

PMID- 29202422
TI  - Dependence of samarium-soil interaction on samarium concentration: Implications
      for environmental risk assessment.
AB  - The sorption and desorption behaviour of samarium (Sm), an emerging contaminant,
      was examined in soil samples at varying Sm concentrations. The obtained sorption
      and desorption parameters revealed that soil possessed a high Sm retention
      capacity (sorption was higher than 99% and desorption lower than 2%) at low Sm
      concentrations, whereas at high Sm concentrations, the sorption-desorption
      behaviour varied among the soil samples tested. The fractionation of the Sm
      sorbed in soils, obtained by sequential extractions, allowed to suggest the soil
      properties (pH and organic matter solubility) and phases (organic matter,
      carbonates and clay minerals) governing the Sm-soil interaction. The sorption
      models constructed in the present work along with the sorption behaviour of Sm
      explained in terms of soil main characteristics will allow properly assessing the
      Sm-soil interaction depending on the contamination scenario under study.
      Moreover, the sorption and desorption Kd values of radiosamarium in soils were
      strongly correlated with those of stable Sm at low concentrations (r = 0.98);
      indicating that the mobility of Sm radioisotopes and, thus, the risk of
      radioactive Sm contamination can be predicted using data from low concentrations
      of stable Sm.

PMID- 29202423
TI  - Suicide and self harm in Nepal: A scoping review.
AB  - BACKGROUND: Suicide and self harm behavior has become a major public health issue
      in recent years in Nepal. This small south Asian country was ranked 7th by
      suicide rate globally by the 2014 World Health Organization report with an
      estimated 6,840 suicides annually, or 24.9 suicides per 100,000 people. We
      decided to explore the epidemiology of suicidal behaviour and self harm, modes of
      attempt, associated risk factors and trends in specific population. METHODOLOGY:
      Two researchers independently reviewed 47 studies published in the US National
      Library of Medicine's PubMed electronic Database and Google Scholar till December
      2016. Finally, twenty articles meeting the objective were included. This article
      summarizes findings on epidemiology of suicidal behavior, associated patterns,
      risk factors and trend in specific population in Nepal. RESULTS: Most of the data
      available till date are hospital based and either cross-sectional or
      retrospective. Some of the studies have relied on mortality statistics whereas
      few have done community based screening. Some of the key findings include higher
      rate among women and younger age group, a rising trend among specific groups such
      as marginalized, migrant workers and disaster affected population. The studies
      also show role of mental illness, predominantly mood disorders and psycho-social
      factors such as interpersonal or marital conflicts and socio-economic issues in
      triggering suicide and self harm behavior. CONCLUSION: Overall, the studies
      provide satisfactory information about the burden of suicide in Nepal. Some of
      the limitations include discrepancy in suicide reporting, lack of longitudinal
      follow up and qualitative studies and absence of studies on preventive aspects.
      Further, more research is warranted in this area not only at the assessment level
      but also at an intervention level. Several challenges such as poor distribution
      of mental health resources, social attitude towards mental illness and suicide in
      particular need to be addressed.

PMID- 29202424
TI  - Genocide in the Philippines.

PMID- 29202425
TI  - Association study of methylenetetrahydrofolate reductase genetic polymorphism
      677C>T with schizophrenia in hospitalized patients in population of European
      Russia.
AB  - The purpose of the research was to investigate the association of
      methylenetetrahydrofolate reductase (hereinafter MTHFR) genetic polymorphism
      677C>T with schizophrenia in the Russian population in comparison with the
      control group of healthy blood donors. Also some characteristics of schizophrenia
      were examined in patients with/without defective T-allele of MTHFR677C>T
      polymorphism. 500 patients with schizophrenia and 499 blood donors were examined
      for T-allele carriage of polymorphism MTHFR677C>T by PCR method. 150 archival
      medical records were studied (in the first patients included in the study). The
      carriage of T-allele of genetic polymorphism MTHFR677C>T was significantly more
      common in patients than in healthy donors: 255/500 versus 219/499 (p=0,0287,
      chi2=4,79; OR=1,33, 95%CI [1037; 1707]). The number of patients with chronic type
      of schizophrenia onset was significantly more among T-allele carriers (n=77) than
      among normal CC-genotype carriers (n=73): r=0.038. The number of "incapacitated"
      persons in the group of patients with defective T-allele (n=77) was significantly
      higher than in patients with normal genotype (n=73, p=0.0439; OR=2.878,
      95%CI=1.111-7.456). The results suggest that T-allele of genetic polymorphism
      MTHFR677C>T in the population of European Russia may increase the risk of
      developing schizophrenia and its unfavorable prognosis, which requires further
      investigation.

PMID- 29202426
TI  - Efficacy and tolerability of long acting injectable antipsychotics (LAI) over
      oral formulations.

PMID- 29202427
TI  - Religiosity and religious delusions in schizophrenia - An observational study in
      a Hindu population.
AB  - BACKGROUND: Religion exerts a significant effect on the lives of many individuals
      including people with mental illness. As evidences keep accumulating, role of
      religion in mental illness is gaining importance. OBJECTIVES: The study was
      designed to study the effects of religiosity on religious delusions, its
      presentation, acute course and outcome in schizophrenia. METHOD: The study was a
      naturalistic observational study. Subjects with schizophrenia were grouped into
      those with religious (RG) and with non-religious delusions (NG). Their premorbid
      religiosity was assessed with Brief Multi-dimensional measurement of
      Religiosity/spirituality (BMMRS) and were rated on Scale for Assessment of
      Positive Symptoms (SAPS), Brown's Assessment of Belief Scale (BABS) and Positive
      and Negative Symptom Scale (PANSS) at baseline and 4 weeks. RESULTS: Scores on
      private religious practices, baseline scores of SAPS, BABS & PANSS and duration
      of untreated psychosis (DUP) were significantly higher for RG in comparison to
      NG. On component analysis, higher scores were seen on private praying, watching
      religious programs on TV, reading religious books and prayers at meals. But no
      significant correlation was found between the private religious practices and the
      baseline scores of (DUP), SAPS, BABS, PANSS and outcome measure. Also no
      significant difference was noted in measures of improvement between groups.
      CONCLUSION: Private religious practices are more prominent in patients of
      schizophrenia with religious delusions and this group of patient seems to present
      with a more severe illness, and a longer duration of untreated psychosis in
      comparison to those with non-religious delusions.

PMID- 29202428
TI  - Factors influencing participation of psychiatry inpatients in clinical trials.
AB  - Serious concerns have arisen in recent years regarding the unethical and illegal
      practices resorted to during clinical trials. Clinical trials in psychiatry are
      further complicated by issues such as 'validity of consent' and 'decision making
      capacity' of patients. This study was planned to explore the factors determining
      patient participation in clinical trials. A random sample of 123 consenting
      psychiatry inpatients were provided the information and consent-form of a
      hypothetical clinical drug trial. They were interviewed regarding their decision,
      the decision maker and factors that led to the decision. Family members tended to
      be the decision makers when patients were females, had low-income, were from
      rural background or had severe illnesses. Anticipated side effects and not
      wanting to interfere with existing treatment were the common reasons for refusal
      to participate while hope of betterment of the patient and benefit to humanity
      were cited for consent. The educated, urban, affluent class had more awareness
      regarding unethical trials and tended to be mistrustful of the medical community
      leading to higher rates of non-participation. Those who were adherent with
      ongoing treatment were also unwilling to participate. The lesser educated, low
      income patients and rural domicile patients on the other hand had lesser
      awareness regarding clinical trials, trusted doctors and were more likely to
      participate. A good doctor-patient relationship, detailed explanations and
      clarification regarding the study and its conduct, and building awareness
      regarding clinical trials among vulnerable groups is necessary to ensure a valid
      consent involving no coercion, removal of prejudices, and ethical conduct of
      trials.

PMID- 29202429
TI  - Low back pain and disability in individuals with plantar heel pain.
AB  - BACKGROUND: Lack of response to plantar heel pain (PHP) treatment may be related
      to unmanaged low back pain (LBP) and low back dysfunction, but a relationship
      between LBP and PHP has not been established. The purpose of this investigation
      was to compare the prevalence of LBP among individuals with and without PHP and
      to assess the association between low back disability and foot/ankle function.
      METHODS: A cross-sectional study compared the prevalence and likelihood of LBP in
      individuals with (n=27) and without (n=27) PHP matched to age, sex, BMI, foot
      posture, and foot mobility. In individuals with PHP, correlations were examined
      between foot/ankle function using the foot and ankle ability measure (FAAM), low
      back disability using the Oswestry low back disability questionnaire (OSW),
      duration of PHP symptoms, body mass index (BMI), and age. RESULTS: A greater
      percentage of individuals with PHP had LBP (74% versus 37% of controls, odds
      ratio=5.2, P=0.009) and higher levels of low back disability (17% higher OSW
      score than controls, P<0.001). In individuals with PHP, FAAM scores were
      correlated with OSW scores (rho=-0.463, P=0.015), but not with duration of PHP
      symptoms, BMI, or age (P>0.150). CONCLUSIONS: Individuals with PHP had a greater
      prevalence of LBP and higher low back disability that was correlated to reduced
      foot and ankle function. Treatment to address both local and proximal
      impairments, including impairments related to LBP, may be warranted to improve
      the management of PHP.

PMID- 29202430
TI  - A retrospective audit of lesion excision and rotation skin flap for the treatment
      of intractable plantar keratosis.
AB  - AIM: The purpose of this study was to evaluate the treatment of plantar skin
      lesions by excision and rotation skin flap closure with reference to patient
      satisfaction; patient reported outcomes and complication rates. METHOD: A
      retrospective audit of 54 consecutive patients who had undergone plantar lesion
      excision with rotation skin flap between May 2011 and November 2015 under the
      care of experienced consultant podiatric surgeons. A total of 36 patients were
      included in this study, 16 were lost to follow up, 2 patients were excluded due
      to non-related pathology. Outcomes were reviewed retrospectively via data
      extracted from PASCOM-10. This included the MOXFQ and also the PSQ-10 patient
      satisfaction questionnaire. Data extracted was analysed. RESULTS: The mean MOXFQ
      scores improved across the three domains. Walking/standing improved from 68.75
      (SD: 17.62) pre-operative to 41.38 (SD: 32.94) post-operative. Pain improved from
      63.47 (SD: 19.41) pre-operative to 36.53 (SD: 25.51) post-operative and social
      interaction improved from 53.88 (SD: 20.33) pre-operative to 29.13 (SD: 26.56)
      post-operative. Similarly, the PSQ-10 scores have shown positive outcomes where
      88.9% out of the cohort felt that their aims of surgery had been met. CONCLUSION:
      This audit has demonstrated that the Schrudde flap is an effective and
      alternative safe surgical procedure for the treatment of intractable plantar
      keratosis and viral warts.

PMID- 29202431
TI  - Triple negative breast cancer: Emerging therapeutic modalities and novel
      combination therapies.
AB  - Triple negative breast cancer (TNBC) is a complex and aggressive subtype of
      breast cancer which lacks oestrogen receptors, progesterone receptors and HER2
      amplification, thereby making it difficult to target therapeutically. In
      addition, TNBC has the highest rates of metastatic disease and the poorest
      overall survival of all breast cancer subtypes. Resultantly, development of
      targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular
      characterisation of TNBCs have revealed various emerging therapeutic targets
      including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints,
      androgen receptor and epigenetic proteins. Key successes include that of the PARP
      inhibitor, olaparib, which prolonged progression-free survival in a trial of BRCA
      mutated breast cancer and for which clinical approval (in this setting) appears
      imminent. Nevertheless, the heterogeneity of TNBC has limited the clinical
      benefits of many trialled therapies in 'unselected' patients. Further, drug
      resistance develops following use of many targeted monotherapies due to
      upregulation of compensatory signalling pathways. In this review, we evaluate the
      current status of investigational targeted treatments and present evidence for
      the role of novel biomarkers and combination therapies in increasing response
      rates and circumventing drug-induced resistance. Additionally, we discuss
      promising novel targets in metastatic TNBC identified through preclinical and/or
      epidemiological studies.

PMID- 29202432
TI  - Validation of the Prognosis for Prolonged Ventilation (ProVent) score in patients
      receiving 14days of mechanical ventilation.
AB  - PURPOSE: To evaluate the performance of the Prognosis for Prolonged Ventilation
      (ProVent) 14 score in patients requiring prolonged mechanical ventilation (PMV).
      MATERIALS AND METHODS: Data were obtained from 366 patients receiving at least
      14days of MV between January 2011 and December 2015 at a university-affiliated
      tertiary care hospital in Korea. ProVent 14 scores were assessed using the six
      standard variables. Model discrimination was assessed with the area under the
      receiver operating characteristic curve. Kaplan-Meier estimates were stratified
      according to the ProVent 14 score to predict 1-year survival. RESULTS: The median
      age of the study group was 62years (range, 50-72years); 65% were male, and
      medical patients comprised 66% of the group. Overall mortality at 1year was 43%.
      For ProVent 14 scores ranging from 0 to >=4, 1-year mortality rates were 7%, 22%,
      41%, 52%, and 75%, respectively (log-rank test, P<0.001). The area under the
      receiver operating characteristic curve of the ProVent 14 score predicting 1-year
      mortality was 0.74 (95% confidence interval, 0.69-0.78). CONCLUSIONS: The ProVent
      14 score accurately identified patients receiving PMV with a high 1-year
      mortality risk. Further validation in a larger sample is required.

PMID- 29202433
TI  - Exploring local people's views on the livelihood impacts of privately versus
      community managed conservation strategies in the Ruvuma landscape of North
      Mozambique-South Tanzania.
AB  - It is broadly acknowledged that natural resources conservation strategies affect
      the livelihoods of local communities. Moreover, evidence suggests that these
      livelihood impacts, in turn, can influence conservation achievements. Yet, what
      constitutes a conservation strategy that communities perceive as acceptable and
      thus they would be willing to commit to over time remains poorly understood. This
      study explores the perceptions of communities regarding the effects of two
      different conservation strategies in the Ruvuma landscape: governmental land
      concessions and licenses to private tourist operators in North Mozambique, versus
      community-managed protected areas supported by NGOs in South Tanzania. The study
      engages communities in a series of semi-structured discussions about natural
      resource use, impact of the conservation strategies on their livelihoods,
      pressures on natural resources, and ways to address such pressures and reach an
      acceptable conservation strategy, from a community perspective. Our findings
      suggest that communities perceive as non-affordable current opportunity and
      damage costs in subsistence agriculture. A strategy integrating improved
      agricultural production, common use of the forest managed by communities, and
      joint ventures between communities and private companies for getting more
      benefits from trophy hunting are identified as acceptable.

PMID- 29202434
TI  - Cypermethrin induced toxicities in fish and adverse health outcomes: Its
      prevention and control measure adaptation.
AB  - Pesticides are being widely employed in the modern agriculture, though in
      different quantities, across the globe. Although it is useful for crops yield
      enhancement, however, there are the serious environment, health and safety
      related concerns for aquatic and terrestrial living biomes that include humans,
      animals, and plants. Various in practice and emerging pesticides adversely affect
      the survival, development and biological systems stability. Several research
      efforts have been made to highlight the bio-safety and toxicological features of
      toxicants through risk assessment studies using different animal models, e.g.,
      different fish species. Among several pesticides, cypermethrin is extensively
      used in agriculture and households, and the reported concentrations of this
      pesticide in different water bodies including rivers and streams, soil and even
      in rainwater are threatening. Consequently, cypermethrin is considered for risk
      assessment studies to know about its deep and different level of toxicological
      effects subject to its dose, exposure time and route. The cypermethrin
      existence/persistence in the environment is posing a severe threat to humans as
      well as another non-target terrestrial and aquatic organism. Herein, the toxic
      effects of pesticides, with special reference to cypermethrin, on fish, the mode
      of toxicity, concerns regarding public health and harmful impacts on human beings
      are comprehensively reviewed. The information is also given on their appropriate
      control and prevention strategies.

PMID- 29202435
TI  - Surface modification of polymeric foams for oil spills remediation.
AB  - In the last decade, a continuous increasing research activity is focused on the
      surface functionalization of polymeric porous materials for the efficient removal
      of oil contaminants from water. This work reviews the most significant recent
      studies on the functionalization of polyurethane and melamine foams, materials
      commonly reported for oil-water separation applications. After the identification
      of the key features of the foams required to optimize their oil removal
      performance, a wide variety of physicochemical treatments are described together
      with their effect on the oil absorption selectivity and oil absorption capacity,
      both critical parameters for the application of the foams in the remediation of
      oil spills. The efficiencies of the different functionalization processes on the
      same type of foams are compared, determining the main advantages and
      potentialities of each treatment and remediation procedure.

PMID- 29202436
TI  - Visual detection of cyanide ions by membrane-based nanozyme assay.
AB  - In this paper, we report a simple one-step synthesis of well-dispersed amorphous
      cobalt hydroxide/oxide-modified graphene oxide (CoOxH-GO) possessing peroxidase
      like catalytic activity, and its application for the detection of H2O2, glucose,
      and CN- ions. CoOxH is formed and deposited in situ on the GO surface through the
      reaction between GO (size ~ 240nm) and Co2+ in basic solution at room
      temperature. We investigated the enzyme-mimicking activity of the CoOxH-GO
      nanohybrid in detail via the H2O2-mediated oxidation of Amplex Red (AR) to form
      fluorescent resorufin. The peroxidase-like activity of CoOxH-GO is utilized
      herein for the quantitation of H2O2 in a wide concentration range, from 100nM to
      100MUM. When coupled with glucose oxidase (GOD), the AR/CoOxH-GO system can
      determine glucose level in blood samples. Interestingly, cyanide ions (CN-)
      significantly inhibit the catalytic activity of the CoOxH-GO nanohybrid, which
      allows for the construction of a probe for the detection of CN- in water samples
      and laboratory wastes. We fabricated a membrane-based CoOxH-GO probe for the
      visual detection of CN- by preparing a thin film of CoOxH-GO on a positively
      charged and porous nylon membrane (N+M). The CoOxH-GO/N+M operates on the
      principle that CN- inhibits the catalytic activity of CoOxH-GO towards the H2O2
      mediated oxidation of AR to form reddish resorufin on the membrane. The intensity
      of the red color of the membrane decreases with increasing CN- concentration,
      which can be easily observed with the naked eye at the nanomolar level. This cost
      effective sensing system allows for the rapid and simple determination of the
      concentrations of CN- in complicated wastewater samples.

PMID- 29202437
TI  - Converting pyrophosphate generated during loop mediated isothermal amplification
      to ATP: Application to electrochemical detection of Nosema bombycis genomic DNA
      PTP1.
AB  - Traditionally, genomic DNA detection is relay on a rigorous DNA amplification
      process, which always accompanied with complicated gel electrophoresis or
      expensive fluorescence detection methods. In this work, we have translated
      genomic DNA detection into adenosine triphosphate (ATP) test based on a split
      aptamer-based electrochemical sandwich assay. The key characteristic of our
      method are list as follows: first, nucleic acid amplification of the target gene
      was performed by the use of a loop mediated isothermal amplification (LAMP)
      process. The pyrophosphate (PPi), which released as the byproduct during the LAMP
      reaction, were further converted into ATP in the presence of adenosine 5'
      phosphosulfate (APS) and ATP sulfurylase. Thereafter, the converted ATP was
      detected by constructing an electrochemical sandwich aptasensor. With such
      design, the conversion from the difficult detecting target (genomic DNA) into a
      convenient measured object (ATP) has been achieved. This proposed strategy was
      highly sensitive for Nosema bombycis genomic DNA PTP1 detection with a detection
      limit as low as 0.47 fg/MUL and a linear range from 0.001pg/MUL to 50ng/MUL. And
      we supposed that this novel target conversion electroanalytical strategy
      established a universal approach for quantitative analysis of any other kinds of
      nucleic acid in assistance of nucleic acid polymerization reaction.

PMID- 29202438
TI  - Spatial-resolved dual-signal-output electrochemiluminescent ratiometric strategy
      for accurate and sensitive immunoassay.
AB  - The identification of tumor markers is of great importance for clinical diagnosis
      but accurate detection with high sensitivity is still a great challenge. In
      present work, a spatial-resolved dual-signal-output electrochemiluminescent (ECL)
      ratiometric assay platform was constructed for sensitive detection of prostate
      specific antigen (PSA) on a dual-disk glassy carbon electrode. To fabricate the
      platform, flower-like CdS three-dimensional (3D) assemblies and Ru(bpy)32+
      conjugated silica nanoparticles (Ru(bpy)32+@RuSi NPs), were immobilized onto the
      two disks as cathodic and anodic ECL emitters, respectively. After the stepwise
      modification of the gold nanoparticles, antibody for PSA, and bovine serum
      albumin onto the two disks respectively, the Ru(bpy)32+@RuSi NPs-based disk were
      incubated with varied concentration of PSA as working electrode, whereas the
      flower-like CdS 3D assemblies-based disk with fixed concentration of PSA were
      taken as internal reference electrode. The label free assay of PSA was realized
      by the ratio of anodic ECL signal from working electrode to the cathodic ECL
      signal from the internal reference electrode (ECLanode/ECLcathode). On the basis
      of the spatial-resolved dual-signal-output ratiometric ECL sensor, the PSA can be
      detected accurately with a linear range of 0.001 - 50ng/mL at a concentration as
      low as 0.34pg/mL. Furthermore, the proposed method was applied for PSA
      determination in human serum samples with satisfying results. Thanks to the same
      modified process of the two disks, this universal design well avoids
      environmental errors including the interference caused in the biological
      recognition process, which effectively reduces the false positive or negative
      errors, exhibiting a greatly improved accuracy, reliability and sensitivity.

PMID- 29202439
TI  - Assessment of mefenamic acid polymorphs in commercial tablets using chemometric
      coupled to MIR and NIR spectroscopies. Prediction of dissolution performance.
AB  - Mefenamic Acid (MFA) is a widely-used non-steroidal anti-inflammatory drug. MFA
      presents four possible crystal forms; Form I and Form II being the only two pure
      crystals that have been isolated and fully characterized. Both Form I and Form II
      were prepared following the literature and completely characterized by middle
      (MIR) and near (NIR) infrared spectroscopy, digital optical microscopy,
      differential scanning calorimetry, melting point and dissolution properties. In
      order to develop quantitative models to assess Form I in formulated products, two
      sets of samples, training (n=10) and validation (n=8) sets, were prepared by
      mixing both polymorphs and the matrix of excipient (simulating commercial
      tablets). The particle size of the samples was homogenized by sieving and samples
      were mechanically mixed. A batch of commercial tablets was gently disaggregated,
      sieved and mechanically mixed for further analysis. For each sample, full MIR and
      NIR spectra were acquired and used as input of partial least squares (PLS)
      algorithm separately. Method optimization and internal validation were performed
      by leave one out procedure. Full spectra and 5 PLS-factors were used for MIR;
      while, 5 PLS-factors and mean center spectra of full spectra were the optimal
      conditions for NIR. Accuracy and precision were assessed by evaluation of the
      actual vs. predicted curve of validation set; and by calculating validation set
      recoveries and deviations (104.3+/-8.2% and 100.4+/-1.0% for MIR and NIR
      respectively). Only NIR-PLS yielded acceptable results and low deviations during
      commercial samples evaluation (102.8+/-0.1%). The same behavior was observed when
      spiked tablets were analyzed (103.5+/-0.5%). Additionally, for the calibration
      set ten dissolution profiles (average of 6 curves each), were obtained under
      optimized test conditions (900 ml of buffer phosphate pH 9 with surfactant,
      apparatus II USP, 100rpm, detection at 342nm). A multiple linear regression (MLR)
      was carried out using dissolution profiles and Form I content. The developed MLR
      model could correlate dissolution profiles and polymorphic richness. This
      approach, coupled to previously developed NIR-PLS, may act as a valid tool to
      estimate dissolution profiles from solid forms.

PMID- 29202440
TI  - Mixture design applied in compatibility studies of catechin and lipid compounds.
AB  - The aim of this work was to evaluate the compatibility of (+)-catechin (CA) and
      excipients commonly used to prepare micro and nanoemulsions using thermal
      analysis along with complementary assays. Lipid compounds labrasol, plurol and
      ethyl oleate were combined with CA according to a simplex centroid mixture design
      and possible interactions between them were determined. Differential scanning
      calorimetry and thermogravimetric analyses were carried out together with Fourier
      transform infrared spectroscopy (FTIR) and morphologic characterization of the
      samples. A quantitative evaluation of thermal events involved in CA melting peak
      and initial sample decomposition temperature were performed. FTIR evaluation
      suggested an initial decomposition of CA mixtures exposed to a thermal aging
      depending on their composition corroborated by the darkening of these samples.
      The multiple regression analysis considering the thermal data revealed a thermal
      interaction compromising CA stability in multicomponent samples. Mixtures
      containing ethyl oleate exhibited a negative synergic action of this fatty acid
      with the others two lipid compounds (negative coefficients for two-factor and
      three-factor interaction terms). Indeed, samples decomposition was anticipated by
      at least 10 degrees C in the case of ternary and quaternary mixtures containing
      ethyl oleate. In conclusion, CA formulations produced with lipid components must
      have their stability closely monitored and production process involving heating
      should be avoided, especially in formulations containing ethyl oleate.

PMID- 29202441
TI  - Income, egalitarianism and attitudes towards healthcare policy: a study on public
      attitudes in 29 countries.
AB  - OBJECTIVES: To evaluate the relationship between income and egalitarian values
      and attitudes towards healthcare policy. STUDY DESIGN: Cross-sectional and cross
      national study. METHODS: Data for 29 countries from the International Social
      Survey Programme (ISSP) 2011 were used. The dependent variables are a general
      attitude towards government involvement in healthcare provision and two attitudes
      regarding specific policies (taxes and public funding). Income and egalitarianism
      were also measured by using ISSP. Data were analysed using regression models that
      account for individual and country-level characteristics, and country-fixed
      effects. RESULTS: The effect of income is small and non-significant for attitudes
      towards government involvement and public funding. For willingness to pay (WTP)
      taxes to improve healthcare services, we find a positive association with income.
      Results for egalitarianism suggest a positive association with government
      involvement in healthcare provision and significant interactions with WTP taxes.
      CONCLUSIONS: The distinction of dimensions and mechanisms underlying policy
      attitudes appears as relevant. Citizens across socioeconomic groups are motivated
      to support state-funded healthcare, favouring the design of non-selfish policies.
      These findings suggest that there is space for policymakers who seek to increase
      healthcare spending encouraging either policies for specific groups or broader
      institutional changes.

PMID- 29202442
TI  - Molecular simulations of the ribosome and associated translation factors.
AB  - The ribosome is a macromolecular complex which is responsible for protein
      synthesis in all living cells according to their transcribed genetic information.
      Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo
      EM), the structure of the ribosome was resolved at atomic resolution in many
      functional and conformational states. Molecular dynamics simulations have added
      information on dynamics and energetics to the available structural information,
      thereby have bridged the gap to the kinetics obtained from single-molecule and
      bulk experiments. Here, we review recent computational studies that brought
      notable insights into ribosomal structure and function.

PMID- 29202443
TI  - Associations of mindful eating domains with depressive symptoms and depression in
      three European countries.
AB  - OBJECTIVE: To examine associations of mindful eating domains with depressive
      symptoms and depression in three European countries. Moderation by change in
      appetite-with increased appetite as marker for depression with atypical features 
      was also tested. METHODS: Data were collected in Denmark (n = 1522), Spain (n =
      1512) and the Netherlands (n = 1439). Multiple linear and logistic regression
      analyses segregated by country were used to test associations of four mindful
      eating domains (Mindful Eating Behaviour Scale; MEBS) with depressive symptoms
      (continuous score on the Center for Epidemiologic Studies Depression Scale; CES
      D) and depression (score above the CES-D cut-off value, and/or use of
      antidepressants, and/or psychological treatment). Moderation by change in
      appetite was tested with bias-corrected bootstrap confidence intervals. RESULTS:
      The domains Focused Eating, Eating with Awareness and Eating without Distraction
      were significantly negatively associated with depressive symptoms and depression
      in all three countries (e.g. Focused Eating Denmark: B = - 0.71, 95% CI: - 0.87, 
      0.54; OR = 0.89, 95% CI: 0.86, 0.93). The domain Hunger and Satiety Cues (only
      measured in the Netherlands) was significantly positively associated with
      depressive symptoms in the adjusted models (B = 0.09, 95% CI: 0.02, 0.16), but
      not with depression (OR = 1.02, 95% CI: 0.98, 1.05). These associations were
      found for both people with and without increased appetite. LIMITATIONS: The cross
      sectional design, which makes it impossible to draw causal conclusions.
      CONCLUSIONS: The present study indicates that higher scores on three mindful
      eating domains are consistently associated with a lower level of depressive
      symptoms and a lower likelihood of having depression in three European countries.

PMID- 29202444
TI  - Evaluation of the Hospital Anxiety and Depression Scale (HADS) in screening
      stroke patients for symptoms: Item Response Theory (IRT) analysis.
AB  - BACKGROUND: Variations have been reported in the number of underlying constructs
      and choice of thresholds that determine caseness of anxiety and /or depression
      using the Hospital Anxiety and Depression scale (HADS). This study examined the
      properties of each item of HADS as perceived by stroke patients, and assessed the
      information these items convey about anxiety and depression between 3 months to 5
      years after stroke. METHODS: The study included 1443 stroke patients from the
      South London Stroke Register (SLSR). The dimensionality of HADS was examined
      using factor analysis methods, and items' properties up to 5 years after stroke
      were tested using Item Response Theory (IRT) methods, including graded response
      models (GRMs). RESULTS: The presence of two dimensions of HADS (anxiety and
      depression) for stroke patients was confirmed. Items that accurately inferred
      about the severity of anxiety and depression, and offered good discrimination of
      caseness were identified as "I can laugh and see the funny side of things" (Q4)
      and "I get sudden feelings of panic" (Q13), discrimination 2.44 (se = 0.26), and
      3.34 (se = 0.35), respectively. Items that shared properties, hence replicate
      inference were: "I get a sort of frightened feeling as if something awful is
      about to happen" (Q3), "I get a sort of frightened feeling like butterflies in my
      stomach" (Q6), and "Worrying thoughts go through my mind" (Q9). Item properties
      were maintained over time. LIMITATIONS: Approximately 20% of patients were lost
      to follow up. CONCLUSION: A more concise selection of items based on their
      properties, would provide a precise approach for screening patients and for an
      optimal allocation of patients into clinical trials.

PMID- 29202446
TI  - Do employers reward physical attractiveness in transition countries?
AB  - This paper studies the labour market returns to physical attractiveness using
      data from three transition countries of the Caucasus: Armenia, Azerbaijan and
      Georgia. I estimate a large positive effect of attractive looks on males'
      probability of employment. Results from the most comprehensive model suggest a
      marginal effect of 11.1 percentage points. Using a partial identification
      approach, I show that this relationship is likely to be causal. After accounting
      for covariates, particularly measures of human capital, there is no evidence for
      a statistically significant link between females' attractiveness and employment.

PMID- 29202445
TI  - Balancing the benefits and harms of thyroid cancer surveillance in survivors of
      Childhood, adolescent and young adult cancer: Recommendations from the
      international Late Effects of Childhood Cancer Guideline Harmonization Group in
      collaboration with the PanCareSurFup Consortium.
AB  - Radiation exposure to the thyroid gland during treatment of childhood, adolescent
      and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC).
      Surveillance recommendations for DTC vary considerably, causing uncertainty about
      optimum screening practices. The International Late Effects of Childhood Cancer
      Guideline Harmonization Group, in collaboration with the PanCareSurFup
      Consortium, developed consensus recommendations for thyroid cancer surveillance
      in CAYAC survivors. These recommendations were developed by an international
      multidisciplinary panel that included 33 experts in relevant medical specialties
      who used a consistent and transparent process. Recommendations were graded
      according to the strength of underlying evidence and potential benefit gained by
      early detection and appropriate management. Of the two available surveillance
      strategies, thyroid ultrasound and neck palpation, neither was shown to be
      superior. Consequently, a decision aid was formulated to guide the health care
      provider in counseling the survivor. The recommendations highlight the need for
      shared decision making regarding whether to undergo surveillance for DTC and in
      the choice of surveillance modality.

PMID- 29202447
TI  - Bone-forming peptide-3 induces osteogenic differentiation of bone marrow stromal
      cells via regulation of the ERK1/2 and Smad1/5/8 pathways.
AB  - A bone-remodeling imbalance induced by increased bone resorption and osteoclast
      formation causes skeletal diseases such as osteoporosis. Induction of osteogenic
      differentiation of bone marrow stromal cells (BMSCs) leads to bone regeneration.
      Many researchers have tried to develop new adjuvants as specific stimulators of
      bone regeneration for therapeutic use in patients with bone resorption. We tried
      to develop a new adjuvant that has stronger osteogenic differentiation-promoting
      activity than bone morphogenetic proteins (BMPs). In this study, we identified a
      new peptide, which we called bone-forming peptide (BFP)-3, derived from the
      immature precursor of BMP-7. Upon osteogenic differentiation, BMSCs treated with
      BFP-3 exhibited higher alkaline phosphatase (ALP) activity and mineralization
      ability and significantly up-regulated expression of osteogenic genes such as
      ALP, osteocalcin (OC), Osterix, and Runx2 compared with control BMSCs.
      Furthermore, fluorescence-activated cell sorting (FACS) and immunofluorescence
      analyses demonstrated that BFP-3 treatment up-regulated CD44 expression.
      Interestingly, extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad1/5/8
      phosphorylation was increased by BFP-3 treatment during osteogenic
      differentiation. Furthermore, BFP-3-induced osteogenic differentiation was
      significantly decreased by treatment with ERK1/2- and Smad-specific inhibitors.
      These results suggest that BFP-3 plays an important role in regulating osteogenic
      differentiation of BMSCs through increasing levels of osteogenic-inducing factors
      and regulating the ERK1/2 and Smad1/5/8 signaling pathways. Our finding indicates
      that BFP-3 may be a potential new therapeutic target for promoting bone
      formation.

PMID- 29202448
TI  - CD11c+ resident macrophages drive hepatocyte death-triggered liver fibrosis in a
      murine model of nonalcoholic steatohepatitis.
AB  - Although recent evidence has pointed to the role of organ- and pathogenesis
      specific macrophage subsets, it is still unclear which subsets are critically
      involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Using
      melanocortin-4 receptor-deficient (MC4R-KO) mice fed Western diet (WD), which
      exhibit liver phenotypes similar to those of human NASH, we found a histological
      structure, termed hepatic crown-like structure (hCLS), in which CD11c+
      macrophages surround dead/dying hepatocytes, a prominent feature of NASH. Here,
      we demonstrate that hCLS-constituting macrophages could be a novel macrophage
      subset that drives hepatocyte death-triggered liver fibrosis. In an "inducible
      NASH model," hepatocyte death induces hCLS formation and liver fibrosis
      sequentially in the short term. In combination with the long-term WD feeding
      model, we also showed that resident macrophages are a major cellular source of
      CD11c+ macrophages constituting hCLS, which exhibited gene expression profiles
      distinct from CD11c- macrophages scattered in the liver. Moreover, depletion of
      CD11c+ macrophages abolished hCLS formation and fibrogenesis in NASH. Our
      clinical data suggest the role of CD11c+ macrophages in the disease progression
      from simple steatosis to NASH. This study sheds light on the role of resident
      macrophages, in addition to recruited macrophages, in the pathogenesis of NASH.

PMID- 29202449
TI  - Clonal relationships of CSF B cells in treatment-naive multiple sclerosis
      patients.
AB  - A role of B cells in multiple sclerosis (MS) is well established, but there is
      limited understanding of their involvement during active disease. Here, we
      examined cerebrospinal fluid (CSF) and peripheral blood (PB) B cells in treatment
      naive patients with MS or high-risk clinically isolated syndrome. Using flow
      cytometry, we found increased CSF lymphocytes with a disproportionate increase of
      B cells compared with T cells in patients with gadolinium-enhancing (Gd+) lesions
      on brain MRI. Ig gene heavy chain variable region (Ig-VH) repertoire sequencing
      of CSF and PB B cells revealed clonal relationships between intrathecal and
      peripheral B cell populations, which could be consistent with migration of B
      cells to and activation in the CNS in active MS. In addition, we found evidence
      for bystander immigration of B cells from the periphery, which could be supported
      by a CXCL13 gradient between CSF and blood. Understanding what triggers B cells
      to migrate and home to the CNS may ultimately aid in the rational selection of
      therapeutic strategies to limit progression in MS.

PMID- 29202450
TI  - Angiotensin-converting enzyme defines matrikine-regulated inflammation and
      fibrosis.
AB  - The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from
      collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE),
      and it is concomitantly degraded by extracellular leukotriene A4 hydrolase
      (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP,
      yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and
      can, thus, support a sustained neutrophilia. In this study, we sought to
      elucidate if an antiinflammatory system existed to degrade AcPGP that is
      analogous to the PGP-LTA4H axis. We demonstrate that AcPGP is degraded through a
      previously unidentified action of the enzyme angiotensin-converting enzyme (ACE).
      Pulmonary ACE is elevated during episodes of acute inflammation, as a consequence
      of enhanced vascular permeability, to ensure the efficient degradation of AcPGP.
      Conversely, we suggest that this pathway is aberrant in chronic obstructive
      pulmonary disease (COPD) enabling the accumulation of AcPGP. Consequently, we
      identify a potentially novel protective role for AcPGP in limiting pulmonary
      fibrosis and suggest the pathogenic function attributed to ACE in idiopathic
      pulmonary fibrosis (IPF) to be a consequence of overzealous AcPGP degradation.
      Thus, AcPGP seemingly has very divergent roles: it is pathogenic in its capacity
      to drive neutrophilic inflammation and matrix degradation in the context of COPD,
      but it is protective in its capacity to limit fibrosis in IPF.

PMID- 29202451
TI  - Akt3 inhibits adipogenesis and protects from diet-induced obesity via WNK1/SGK1
      signaling
AB  - Three Akt isoforms, encoded by 3 separate genes, are expressed in mammals. While
      the roles of Akt1 and Akt2 in metabolism are well established, it is not yet
      known whether Akt3 plays a role in metabolic diseases. We now report that Akt3
      protects mice from high-fat diet-induced obesity by suppressing an alternative
      pathway of adipogenesis via with no lysine protein kinase-1 (WNK1) and
      serum/glucocorticoid-inducible kinase 1 (SGK1). We demonstrate that Akt3
      specifically phosphorylates WNK1 at T58 and promotes its degradation via the
      ubiquitin-proteasome pathway. A lack of Akt3 in adipocytes increases the WNK1
      protein level, leading to activation of SGK1. SGK1, in turn, promotes
      adipogenesis by phosphorylating and inhibiting transcription factor FOXO1 and,
      subsequently, activating the transcription of PPARgamma in adipocytes. Akt3
      deficient mice have an increased number of adipocytes and, when fed a high-fat
      diet, display increased weight gain, white adipose tissue expansion, and impaired
      glucose homeostasis. Pharmacological blockade of SGK1 in high-fat diet-fed Akt3
      deficient mice suppressed adipogenesis, prevented excessive weight gain and
      adiposity, and ameliorated metabolic parameters. Thus, Akt3/WNK1/SGK1 represents
      a potentially novel signaling pathway controlling the development of obesity.

PMID- 29202452
TI  - Systemic inflammation is associated with exaggerated skeletal muscle protein
      catabolism in maintenance hemodialysis patients.
AB  - BACKGROUND: Systemic inflammation and muscle wasting are highly prevalent and
      coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the
      effects of systemic inflammation on skeletal muscle protein metabolism in MHD
      patients. METHODS: Whole body and skeletal muscle protein turnover were assessed
      by stable isotope kinetic studies. We incorporated expressions of E1, E214K,
      E3alphaI, E3alphaII, MuRF-1, and atrogin-1 in skeletal muscle tissue from
      integrin beta1 gene KO CKD mice models. RESULTS: Among 129 patients with mean (+/
      SD) age 47 +/- 12 years, 74% were African American, 73% were male, and 22% had
      diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP)
      concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically
      significant associations between hs-CRP and forearm skeletal muscle protein
      synthesis, degradation, and net forearm skeletal muscle protein balance (P <
      0.001 for all). The associations remained statistically significant after
      adjustment for clinical and demographic confounders, as well as in sensitivity
      analysis, excluding patients with diabetes mellitus. In attempting to identify
      potential mechanisms involved in this correlation, we show increased expressions
      of E1, E214K, E3alphaI, E3alphaII, MuRF-1, and atrogin-1 in skeletal muscle
      tissue obtained from an animal model of chronic kidney disease. CONCLUSION: These
      data suggest that systemic inflammation is a strong and independent determinant
      of skeletal muscle protein homeostasis in MHD patients, providing rationale for
      further studies using anticytokine therapies in patients with underlying systemic
      inflammation. FUNDING: This study was in part supported by NIH grants R01 DK45604
      and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the
      National Center for Advancing Translational Sciences, the Veterans Administration
      Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant
      Program, and the FDA grant 000943.

PMID- 29202453
TI  - Increased Ca2+ signaling through CaV1.2 promotes bone formation and prevents
      estrogen deficiency-induced bone loss.
AB  - While the prevalence of osteoporosis is growing rapidly with population aging,
      therapeutic options remain limited. Here, we identify potentially novel roles for
      CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a
      transgenic gain-of-function mutant CaV1.2 to stem bone loss in ovariectomized
      female mice. We show that endogenous CaV1.2 is expressed in developing bone
      within proliferating chondrocytes and osteoblasts. Using primary BM stromal cell
      (BMSC) cultures, we found that Ca2+ influx through CaV1.2 activates osteogenic
      transcriptional programs and promotes mineralization. We used Prx1-, Col2a1-, or
      Col1a1-Cre drivers to express an inactivation-deficient CaV1.2 mutant in
      chondrogenic and/or osteogenic precursors in vivo and found that the resulting
      increased Ca2+ influx markedly thickened bone not only by promoting osteogenesis,
      but also by inhibiting osteoclast activity through increased osteoprotegerin
      secretion from osteoblasts. Activating the CaV1.2 mutant in osteoblasts at the
      time of ovariectomy stemmed bone loss. Together, these data highlight roles for
      CaV1.2 in bone and demonstrate the potential dual anabolic and anticatabolic
      therapeutic actions of tissue-specific CaV1.2 activation in osteoblasts.

PMID- 29202454
TI  - Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in
      vitro and in vivo.
AB  - W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]
      benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]
      benzenesulfonamide) represent two emerging drugs of abuse chemically related to
      the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N
      phenylpropanamide). Here, we describe the comprehensive pharmacological profiles
      of W-18 and W-15, as examination of their structural features predicted that they
      might lack opioid activity. We found W-18 and W-15 to be without detectible
      activity at MU, delta, kappa, and nociception opioid receptors in a variety of
      assays. We also tested W-18 and W-15 for activity as allosteric modulators at
      opioid receptors and found them devoid of significant positive or negative
      allosteric modulatory activity. Comprehensive profiling at essentially all the
      druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no
      significant activity. Weak activity at the sigma receptors and the peripheral
      benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity
      in either the radiant heat tail-flick or the writhing assays and also did not
      induce classical opioid behaviors. W-18 is extensively metabolized, but its
      metabolites also lack opioid activity. Thus, although W-18 and W-15 have been
      suggested to be potent opioid agonists, our results reveal no significant
      activity at these or other known targets for psychoactive drugs.

PMID- 29202455
TI  - A simple, clinically relevant therapeutic vaccine shows long-term protection in
      an aggressive, delayed-treatment B lymphoma model.
AB  - Despite initial remission after successful treatments, B lymphoma patients often
      encounter relapses and resistance causing high mortality. Thus, there is a need
      to develop therapies that prevent relapse by providing long-term protection and,
      ultimately, lead to functional cure. In this study, our goal was to develop a
      simple, clinically relevant, and easily translatable therapeutic vaccine that
      provides durable immune protection against aggressive B cell lymphoma and
      identify critical immune biomarkers that are predictive of long-term survival. In
      a delayed-treatment, aggressive, murine model of A20 B lymphoma that mimics human
      diffuse large B cell lymphoma, we show that therapeutic A20 lysate vaccine
      adjuvanted with an NKT cell agonist, alpha-galactosylceramide (alpha-GalCer),
      provides long-term immune protection against lethal tumor challenges and the
      antitumor immunity is primarily CD8 T cell dependent. Using experimental and
      computational methods, we demonstrate that the initial strength of germinal
      center reaction and the magnitude of class-switching into a Th1 type humoral
      response are the best predictors for the long-term immunity of B lymphoma lysate
      vaccine. Our results not only provide fundamentally insights for successful
      immunotherapy and long-term protection against B lymphomas, but also present a
      simple, therapeutic vaccine that can be translated easily due to the facile and
      inexpensive method of preparation.

PMID- 29202456
TI  - Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with
      no effective treatment. We used simple genetic models of ALS to screen
      phenotypically for potential therapeutic compounds. We screened libraries of
      compounds in C. elegans, validated hits in zebrafish, and tested the most potent
      molecule in mice and in a small clinical trial. We identified a class of
      neuroleptics that restored motility in C. elegans and in zebrafish, and the most
      potent was pimozide, which blocked T-type Ca2+ channels in these simple models
      and stabilized neuromuscular transmission in zebrafish and enhanced it in mice.
      Finally, a short randomized controlled trial of sporadic ALS subjects
      demonstrated stabilization of motility and evidence of target engagement at the
      neuromuscular junction. Simple genetic models are, thus, useful in identifying
      promising compounds for the treatment of ALS, such as neuroleptics, which may
      stabilize neuromuscular transmission and prolong survival in this disease.

PMID- 29202457
TI  - Recapitulation of developmental mechanisms to revascularize the ischemic heart.
AB  - Restoring blood flow after myocardial infarction (MI) is essential for survival
      of existing and newly regenerated tissue. Endogenous vascular repair processes
      are deployed following injury but are poorly understood. We sought to determine
      whether developmental mechanisms of coronary vessel formation are intrinsically
      reactivated in the adult mouse after MI. Using pulse-chase genetic lineage
      tracing, we establish that de novo vessel formation constitutes a substantial
      component of the neovascular response, with apparent cellular contributions from
      the endocardium and coronary sinus. The adult heart reverts to its former
      hypertrabeculated state and repeats the process of compaction, which may
      facilitate endocardium-derived neovascularization. The capacity for angiogenic
      sprouting of the coronary sinus vein, the adult derivative of the sinus venosus,
      may also reflect its embryonic origin. The quiescent epicardium is reactivated
      and, while direct cellular contribution to new vessels is minimal, it supports
      the directional expansion of the neovessel network toward the infarcted
      myocardium. Thymosin beta4, a peptide with roles in vascular development, was
      required for endocardial compaction, epicardial vessel expansion, and smooth
      muscle cell recruitment. Insight into pathways that regulate endogenous vascular
      repair, drawing on comparisons with development, may reveal novel targets for
      therapeutically enhancing neovascularization.

PMID- 29202458
TI  - Integrating light-sheet imaging with virtual reality to recapitulate
      developmental cardiac mechanics.
AB  - Currently, there is a limited ability to interactively study developmental
      cardiac mechanics and physiology. We therefore combined light-sheet fluorescence
      microscopy (LSFM) with virtual reality (VR) to provide a hybrid platform for 3D
      architecture and time-dependent cardiac contractile function characterization. By
      taking advantage of the rapid acquisition, high axial resolution, low
      phototoxicity, and high fidelity in 3D and 4D (3D spatial + 1D time or spectra),
      this VR-LSFM hybrid methodology enables interactive visualization and
      quantification otherwise not available by conventional methods, such as routine
      optical microscopes. We hereby demonstrate multiscale applicability of VR-LSFM to
      (a) interrogate skin fibroblasts interacting with a hyaluronic acid-based
      hydrogel, (b) navigate through the endocardial trabecular network during
      zebrafish development, and (c) localize gene therapy-mediated potassium channel
      expression in adult murine hearts. We further combined our batch intensity
      normalized segmentation algorithm with deformable image registration to interface
      a VR environment with imaging computation for the analysis of cardiac
      contraction. Thus, the VR-LSFM hybrid platform demonstrates an efficient and
      robust framework for creating a user-directed microenvironment in which we
      uncovered developmental cardiac mechanics and physiology with high spatiotemporal
      resolution.

PMID- 29202459
TI  - Nasospheroids permit measurements of CFTR-dependent fluid transport.
AB  - Expansion of novel therapeutics to all patients with cystic fibrosis (CF)
      requires personalized CFTR modulator therapy. We have developed nasospheroids, a
      primary cell culture-based model derived from individual CF patients and healthy
      subjects by a minimally invasive nasal biopsy. Confocal microscopy was utilized
      to measure CFTR activity by analyzing changes in cross-sectional area over time
      that resulted from CFTR-mediated ion and fluid movement. Both the rate of change
      over time and AUC were calculated. Non-CF nasospheroids with active CFTR-mediated
      ion and fluid movement showed a reduction in cross-sectional area, whereas no
      changes were observed in CF spheroids. Non-CF spheroids treated with CFTR
      inhibitor lost responsiveness for CFTR activation. However, nasospheroids from
      F508del CF homozygotes that were treated with lumacaftor and ivacaftor showed a
      significant reduction in cross-sectional area, indicating pharmacologic rescue of
      CFTR function. This model employs a simple measurement of size corresponding to
      changes in CFTR activity and is applicable for detection of small changes in CFTR
      activity from individual patients in vitro. Advancements of this technique will
      provide a robust model for individualized prediction of CFTR modulator efficacy.

PMID- 29202460
TI  - Human liver-kidney model elucidates the mechanisms of aristolochic acid
      nephrotoxicity.
AB  - Environmental exposures pose a significant threat to human health. However, it is
      often difficult to study toxicological mechanisms in human subjects due to
      ethical concerns. Plant-derived aristolochic acids are among the most potent
      nephrotoxins and carcinogens discovered to date, yet the mechanism of
      bioactivation in humans remains poorly understood. Microphysiological systems
      (organs-on-chips) provide an approach to examining the complex, species-specific
      toxicological effects of pharmaceutical and environmental chemicals using human
      cells. We microfluidically linked a kidney-on-a-chip with a liver-on-a-chip to
      determine the mechanisms of bioactivation and transport of aristolochic acid I
      (AA-I), an established nephrotoxin and human carcinogen. We demonstrate that
      human hepatocyte-specific metabolism of AA-I substantially increases its
      cytotoxicity toward human kidney proximal tubular epithelial cells, including
      formation of aristolactam adducts and release of kidney injury biomarkers.
      Hepatic biotransformation of AA-I to a nephrotoxic metabolite involves
      nitroreduction, followed by sulfate conjugation. Here, we identify, in a human
      tissue-based system, that the sulfate conjugate of the hepatic NQO1-generated
      aristolactam product of AA-I (AL-I-NOSO3) is the nephrotoxic form of AA-I. This
      conjugate can be transported out of liver via MRP membrane transporters and then
      actively transported into kidney tissue via one or more organic anionic membrane
      transporters. This integrated microphysiological system provides an ex vivo
      approach for investigating organ-organ interactions, whereby the metabolism of a
      drug or other xenobiotic by one tissue may influence its toxicity toward another,
      and represents an experimental approach for studying chemical toxicity related to
      environmental and other toxic exposures.

PMID- 29202461
TI  - IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.
AB  - IL-7 regulates homeostatic mechanisms that maintain the overall size of the T
      cell pool throughout life. We show that, under steady-state conditions, IL-7
      signaling is principally mediated by activation of signal transducers and
      activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions,
      there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1
      and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered
      with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression
      was associated with reduced survival in CD4+ T cells undergoing lymphopenia
      induced proliferation (LIP). We propose a model in which T cells undergoing LIP
      upregulate STAT1 protein, "switching on" an alternate IL-7-dependent program.
      This mechanism could be a physiological process to regulate the expansion and
      size of the CD4+ T cell pool. During HIV infection, the virus could exploit this
      pathway, leading to the homeostatic dysregulation of the T cell pools observed in
      these patients.

PMID- 29202462
TI  - Paracrine osteoprotegerin and beta-catenin stabilization support synovial
      sarcomagenesis in periosteal cells.
AB  - Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma that is often
      discovered during adolescence and young adulthood. Despite the name, synovial
      sarcoma does not typically arise from a synoviocyte but instead arises in close
      proximity to bones. Previous work demonstrated that mice expressing the
      characteristic SS18-SSX fusion oncogene in myogenic factor 5-expressing (Myf5
      expressing) cells develop fully penetrant sarcomagenesis, suggesting skeletal
      muscle progenitor cell origin. However, Myf5 is not restricted to committed
      myoblasts in embryos but is also expressed in multipotent mesenchymal
      progenitors. Here, we demonstrated that human SS and mouse tumors arising from
      SS18-SSX expression in the embryonic, but not postnatal, Myf5 lineage share an
      anatomic location that is frequently adjacent to bone. Additionally, we showed
      that SS can originate from periosteal cells expressing SS18-SSX alone and from
      preosteoblasts expressing the fusion oncogene accompanied by the added
      stabilization of beta-catenin, which is a common secondary change in SS.
      Expression and secretion of the osteoclastogenesis inhibitory factor
      osteoprotegerin enabled early growth of SS18-SSX2-transformed cells, indicating a
      paracrine link between the bone and synovial sarcomagenesis. These findings
      explain the skeletal contact frequently observed in human SS and may provide
      alternate means of enabling SS18-SSX-driven oncogenesis in cells as
      differentiated as preosteoblasts.

PMID- 29202464
TI  - Hedgehog signaling drives medulloblastoma growth via CDK6.
AB  - Medulloblastoma, an aggressive cancer of the cerebellum, is among the most common
      pediatric brain tumors. Approximately one-third of medulloblastomas are
      associated with misactivation of the Hedgehog (Hh) pathway. GLI family zinc
      finger 2 (GLI2) coordinates the Hh transcriptional program; however, the GLI2
      targets that promote cancer cell proliferation are unknown. Here, we incorporated
      a Gli2-EGFP allele into 2 different genetic mouse models of Hh-associated
      medulloblastoma. Hh signaling induced GLI2 binding to the Cdk6 promoter and
      activated Cdk6 expression, thereby promoting uncontrolled cell proliferation.
      Genetic or pharmacological inhibition of CDK6 in mice repressed the growth of Hh
      associated medulloblastoma and prolonged survival through inhibition of cell
      proliferation. In human medulloblastoma, misactivation of Hh signaling was
      associated with high levels of CDK6, pointing to CDK6 as a direct transcriptional
      target of the Hh pathway. These results suggest that CDK6 antagonists may be a
      promising therapeutic approach for Hh-associated medulloblastoma in humans.

PMID- 29202463
TI  - Patients and animal models of CNGbeta1-deficient retinitis pigmentosa support
      gene augmentation approach.
AB  - Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million
      people worldwide. Mutations in cyclic nucleotide-gated channel beta 1 (CNGB1)
      cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows
      promise for treating inherited retinal degenerations; however, relevant animal
      models and biomarkers of progression in patients with RP are needed to assess
      therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for
      potential biomarkers of progression and compared human phenotypes with those of
      mouse and dog models of the disease. Additionally, we used gene augmentation
      therapy in a CNGbeta1-deficient dog model to evaluate potential translation to
      patients. CNGB1-deficient RP patients and mouse and dog models had a similar
      phenotype characterized by early loss of rod function and slow rod photoreceptor
      loss with a secondary decline in cone function. Advanced imaging showed promise
      for evaluating RP progression in human patients, and gene augmentation using
      adeno-associated virus vectors robustly sustained the rescue of rod function and
      preserved retinal structure in the dog model. Together, our results reveal an
      early loss of rod function in CNGB1-deficient patients and a wide window for
      therapeutic intervention. Moreover, the identification of potential biomarkers of
      outcome measures, availability of relevant animal models, and robust functional
      rescue from gene augmentation therapy support future work to move CNGB1-RP
      therapies toward clinical trials.

PMID- 29202465
TI  - Thioesterase-mediated control of cellular calcium homeostasis enables hepatic ER
      stress.
AB  - The incorporation of excess saturated free fatty acids (SFAs) into membrane
      phospholipids within the ER promotes ER stress, insulin resistance, and hepatic
      gluconeogenesis. Thioesterase superfamily member 2 (Them2) is a mitochondria
      associated long-chain fatty acyl-CoA thioesterase that is activated upon binding
      phosphatidylcholine transfer protein (PC-TP). Under fasting conditions, the
      Them2/PC-TP complex directs saturated fatty acyl-CoA toward beta-oxidation. Here,
      we showed that during either chronic overnutrition or acute induction of ER
      stress, Them2 and PC-TP play critical roles in trafficking SFAs into the
      glycerolipid biosynthetic pathway to form saturated phospholipids, which
      ultimately reduce ER membrane fluidity. The Them2/PC-TP complex activated ER
      stress pathways by enhancing translocon-mediated efflux of ER calcium. The
      increased cytosolic calcium, in turn, led to the phosphorylation of
      calcium/calmodulin-dependent protein kinase II, which promoted both hepatic
      insulin resistance and gluconeogenesis. These findings delineate a mechanistic
      link between obesity and insulin resistance and establish the Them2/PC-TP complex
      as an attractive target for the management of hepatic steatosis and insulin
      resistance.

PMID- 29202466
TI  - Loss of pleckstrin-2 reverts lethality and vascular occlusions in JAK2V617F
      positive myeloproliferative neoplasms.
AB  - V617F driver mutation of JAK2 is the leading cause of the Philadelphia-chromosome
      negative myeloproliferative neoplasms (MPNs). Although thrombosis is a leading
      cause of mortality and morbidity in MPNs, the mechanisms underlying their
      pathogenesis are unclear. Here, we identified pleckstrin-2 (Plek2) as a
      downstream target of the JAK2/STAT5 pathway in erythroid and myeloid cells, and
      showed that it is upregulated in a JAK2V617F-positive MPN mouse model and in
      patients with MPNs. Loss of Plek2 ameliorated JAK2V617F-induced
      myeloproliferative phenotypes including erythrocytosis, neutrophilia,
      thrombocytosis, and splenomegaly, thereby reverting the widespread vascular
      occlusions and lethality in JAK2V617F-knockin mice. Additionally, we demonstrated
      that a reduction in red blood cell mass was the main contributing factor in the
      reversion of vascular occlusions. Thus, our study identifies Plek2 as an effector
      of the JAK2/STAT5 pathway and a key factor in the pathogenesis of JAK2V617F
      induced MPNs, pointing to Plek2 as a viable target for the treatment of MPNs.

PMID- 29202467
TI  - Endothelial chimerism and vascular sequestration protect pancreatic islet grafts
      from antibody-mediated rejection.
AB  - Humoral rejection is the most common cause of solid organ transplant failure.
      Here, we evaluated a cohort of 49 patients who were successfully grafted with
      allogenic islets and determined that the appearance of donor-specific anti-HLA
      antibodies (DSAs) did not accelerate the rate of islet graft attrition,
      suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic
      targets expressed by islet cells and induced their destruction in vitro; however,
      passive transfer of the same DSAs did not affect islet graft survival in murine
      models. Live imaging revealed that DSAs were sequestrated in the circulation of
      the recipients and failed to reach the endocrine cells of grafted islets. We used
      murine heart transplantation models to confirm that endothelial cells were the
      only accessible targets for DSAs, which induced the development of typical
      microvascular lesions in allogeneic transplants. In contrast, the vasculature of
      DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of
      recipient capillaries reestablished blood flow in grafted islets. Thus, we
      conclude that endothelial chimerism combined with vascular sequestration of DSAs
      protects islet grafts from humoral rejection. The reduced immunoglobulin
      concentrations in the interstitial tissue, confirmed in patients, may have
      important implications for biotherapies such as vaccines and monoclonal
      antibodies.

PMID- 29202468
TI  - Polycomb subunit BMI1 determines uterine progesterone responsiveness essential
      for normal embryo implantation.
AB  - Natural and synthetic progestogens have been commonly used to prevent recurrent
      pregnancy loss in women with inadequate progesterone secretion or reduced
      progesterone sensitivity. However, the clinical efficacy of progesterone and its
      analogs for maintaining pregnancy is variable. Additionally, the underlying cause
      of impaired endometrial progesterone responsiveness during early pregnancy
      remains unknown. Here, we demonstrated that uterine-selective depletion of BMI1,
      a key component of the polycomb repressive complex-1 (PRC1), hampers uterine
      progesterone responsiveness and derails normal uterine receptivity, resulting in
      implantation failure in mice. We further uncovered genetic and biochemical
      evidence that BMI1 interacts with the progesterone receptor (PR) and the E3
      ligase E6AP in a polycomb complex-independent manner and regulates the PR
      ubiquitination that is essential for normal progesterone responsiveness. A close
      association of aberrantly low endometrial BMI1 expression with restrained PR
      responsiveness in women who had previously had a miscarriage indicated that the
      role of BMI1 in endometrial PR function is conserved in mice and in humans. In
      addition to uncovering a potential regulatory mechanism of BMI1 that ensures
      normal endometrial progesterone responsiveness during early pregnancy, our
      findings have the potential to help clarify the underlying causes of spontaneous
      pregnancy loss in women.

PMID- 29202469
TI  - H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition.
AB  - Uncovering the causes of pregnancy complications such as preterm labor requires
      greater insight into how the uterus remains in a noncontractile state until term
      and then surmounts this state to enter labor. Here, we show that dynamic
      generation and erasure of the repressive histone modification tri-methyl histone
      H3 lysine 27 (H3K27me3) in decidual stromal cells dictate both elements of
      pregnancy success in mice. In early gestation, H3K27me3-induced transcriptional
      silencing of select gene targets ensured uterine quiescence by preventing the
      decidua from expressing parturition-inducing hormone receptors, manifesting type
      1 immunity, and most unexpectedly, generating myofibroblasts and associated wound
      healing responses. In late gestation, genome-wide H3K27 demethylation allowed for
      target gene upregulation, decidual activation, and labor entry. Pharmacological
      inhibition of H3K27 demethylation in late gestation not only prevented term
      parturition, but also inhibited delivery while maintaining pup viability in a
      noninflammatory model of preterm parturition. Immunofluorescence analysis of
      human specimens suggested that similar regulatory events might occur in the human
      decidua. Together, these results reveal the centrality of regulated gene
      silencing in the uterine adaptation to pregnancy and suggest new areas in the
      study and treatment of pregnancy disorders.

PMID- 29202470
TI  - Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit
      adipogenesis.
AB  - The molecular mechanisms that transduce the osteoblast response to physical
      forces in the bone microenvironment are poorly understood. Here, we used genetic
      and pharmacological experiments to determine whether the polycystins PC1 and PC2
      (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a
      mechanosensing complex in osteoblasts. Compound-heterozygous mice lacking 1 copy
      of Pkd1 and Taz exhibited additive decrements in bone mass, impaired osteoblast
      mediated bone formation, and enhanced bone marrow fat accumulation. Bone marrow
      stromal cells and osteoblasts derived from these mice showed impaired
      osteoblastogenesis and enhanced adipogenesis. Increased extracellular matrix
      stiffness and application of mechanical stretch to multipotent mesenchymal cells
      stimulated the nuclear translocation of the PC1 C-terminal tail/TAZ (PC1-CTT/TAZ)
      complex, leading to increased runt-related transcription factor 2-mediated (Runx2
      mediated) osteogenic and decreased PPARgamma-dependent adipogenic gene
      expression. Using structure-based virtual screening, we identified a compound
      predicted to bind to PC2 in the PC1:PC2 C-terminal tail region with helix:helix
      interaction. This molecule stimulated polycystin- and TAZ-dependent
      osteoblastogenesis and inhibited adipogenesis. Thus, we show that polycystins and
      TAZ integrate at the molecular level to reciprocally regulate osteoblast and
      adipocyte differentiation, indicating that the polycystins/TAZ complex may be a
      potential therapeutic target to increase bone mass.

PMID- 29202471
TI  - Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor
      metastases in bone.
AB  - During tumor progression, immune system phagocytes continually clear apoptotic
      cancer cells in a process known as efferocytosis. However, the impact of
      efferocytosis in metastatic tumor growth is unknown. In this study, we observed
      that macrophage-driven efferocytosis of prostate cancer cells in vitro induced
      the expression of proinflammatory cytokines such as CXCL5 by activating Stat3 and
      NF-kappaB(p65) signaling. Administration of a dimerizer ligand (AP20187)
      triggered apoptosis in 2 in vivo syngeneic models of bone tumor growth in which
      apoptosis-inducible prostate cancer cells were either coimplanted with vertebral
      bodies, or inoculated in the tibiae of immunocompetent mice. Induction of 2
      pulses of apoptosis correlated with increased infiltration of inflammatory cells
      and accelerated tumor growth in the bone. Apoptosis-induced tumors displayed
      elevated expression of the proinflammatory cytokine CXCL5. Likewise, CXCL5
      deficient mice had reduced tumor progression. Peripheral blood monocytes isolated
      from patients with bone metastasis of prostate cancer were more efferocytic
      compared with normal controls, and CXCL5 serum levels were higher in metastatic
      prostate cancer patients relative to patients with localized prostate cancer or
      controls. Altogether, these findings suggest that the myeloid phagocytic
      clearance of apoptotic cancer cells accelerates CXCL5-mediated inflammation and
      tumor growth in bone, pointing to CXCL5 as a potential target for cancer
      therapeutics.

PMID- 29202472
TI  - Hyposialylated IgG activates endothelial IgG receptor FcgammaRIIB to promote
      obesity-induced insulin resistance.
AB  - Type 2 diabetes mellitus (T2DM) is a common complication of obesity. Here, we
      have shown that activation of the IgG receptor FcgammaRIIB in endothelium by
      hyposialylated IgG plays an important role in obesity-induced insulin resistance.
      Despite becoming obese on a high-fat diet (HFD), mice lacking FcgammaRIIB
      globally or selectively in endothelium were protected from insulin resistance as
      a result of the preservation of insulin delivery to skeletal muscle and resulting
      maintenance of muscle glucose disposal. IgG transfer in IgG-deficient mice
      implicated IgG as the pathogenetic ligand for endothelial FcgammaRIIB in obesity
      induced insulin resistance. Moreover, IgG transferred from patients with T2DM but
      not from metabolically healthy subjects caused insulin resistance in IgG
      deficient mice via FcgammaRIIB, indicating that similar processes may be
      operative in T2DM in humans. Mechanistically, the activation of FcgammaRIIB by
      IgG from obese mice impaired endothelial cell insulin transcytosis in culture and
      in vivo. These effects were attributed to hyposialylation of the Fc glycan, and
      IgG from T2DM patients was also hyposialylated. In HFD-fed mice, supplementation
      with the sialic acid precursor N-acetyl-D-mannosamine restored IgG sialylation
      and preserved insulin sensitivity without affecting weight gain. Thus, IgG
      sialylation and endothelial FcgammaRIIB may represent promising therapeutic
      targets to sever the link between obesity and T2DM.

PMID- 29202473
TI  - FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated
      intestinal inflammation and barrier dysfunction.
AB  - Foods high in fermentable oligosaccharides, disaccharides, monosaccharides, and
      polyols (FODMAPs) exacerbate symptoms of irritable bowel syndrome (IBS); however,
      their mechanism of action is unknown. We hypothesized that a high-FODMAP (HFM)
      diet increases visceral nociception by inducing dysbiosis and that the FODMAP
      altered gut microbial community leads to intestinal pathology. We fed rats an HFM
      and showed that HFM increases rat fecal Gram-negative bacteria, elevates
      lipopolysaccharides (LPS), and induces intestinal pathology, as indicated by
      inflammation, barrier dysfunction, and visceral hypersensitivity (VH). These
      manifestations were prevented by antibiotics and reversed by low-FODMAP (LFM)
      diet. Additionally, intracolonic administration of LPS or fecal supernatant (FS)
      from HFM-fed rats caused intestinal barrier dysfunction and VH, which were
      blocked by the LPS antagonist LPS-RS or by TLR4 knockdown. Fecal LPS was higher
      in IBS patients than in healthy subjects (HS), and IBS patients on a 4-week LFM
      diet had improved IBS symptoms and reduced fecal LPS levels. Intracolonic
      administration of FS from IBS patients, but not FS from HS or LFM-treated IBS
      patients, induced VH in rats, which was ameliorated by LPS-RS. Our findings
      indicate that HFM-associated gut dysbiosis and elevated fecal LPS levels induce
      intestinal pathology, thereby modulating visceral nociception and IBS
      symptomatology, and might provide an explanation for the success of LFM diet in
      IBS patients.

PMID- 29202474
TI  - ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming.
AB  - Metabolic reprogramming in breast tumors is linked to increases in putative
      oncogenic metabolites that may contribute to malignant transformation. We
      previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate
      (2HG), in breast tumors was associated with MYC signaling, but not with
      isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for
      increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant
      enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial
      enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast
      cancer oncogene that decreases patient survival. We found that MYC upregulates
      ADHFE1 through changes in iron metabolism while coexpression of both ADHFE1 and
      MYC strongly enhanced orthotopic tumor growth in MCF7 cells. Moreover, ADHFE1
      promoted metabolic reprogramming with increased formation of D-2HG and reactive
      oxygen, a reductive glutamine metabolism, and modifications of the epigenetic
      landscape, leading to cellular dedifferentiation, enhanced mesenchymal
      transition, and phenocopying alterations that occur with high D-2HG levels in
      cancer cells with IDH mutations. Together, our data support the hypothesis that
      ADHFE1 and MYC signaling contribute to D-2HG accumulation in breast tumors and
      show that D-2HG is an oncogenic metabolite and potential driver of disease
      progression.

PMID- 29202475
TI  - Discovery, characterization, and clinical development of the glucagon-like
      peptides.
AB  - The discovery, characterization, and clinical development of glucagon-like
      peptide-1 (GLP-1) spans more than 30 years and includes contributions from
      multiple investigators, science recognized by the 2017 Harrington Award Prize for
      Innovation in Medicine. Herein, we provide perspectives on the historical events
      and key experimental findings establishing the biology of GLP-1 as an insulin
      stimulating glucoregulatory hormone. Important attributes of GLP-1 action and
      enteroendocrine science are reviewed, with emphasis on mechanistic advances and
      clinical proof-of-concept studies. The discovery that GLP-2 promotes mucosal
      growth in the intestine is described, and key findings from both preclinical
      studies and the GLP-2 clinical development program for short bowel syndrome (SBS)
      are reviewed. Finally, we summarize recent progress in GLP biology, highlighting
      emerging concepts and scientific insights with translational relevance.

PMID- 29202478
TI  - gammadeltaTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation
      program.
AB  - gammadeltaT cells produce inflammatory cytokines and have been implicated in the
      pathogenesis of cancer, infectious diseases, and autoimmunity. The T cell
      receptor (TCR) signal transduction that specifically regulates the development of
      IL-17-producing gammadeltaT (gammadeltaT17) cells largely remains unclear. Here,
      we showed that the receptor proximal tyrosine kinase Syk is essential for
      gammadeltaTCR signal transduction and development of gammadeltaT17 in the mouse
      thymus. Zap70, another tyrosine kinase essential for the development of
      alphabetaT cells, failed to functionally substitute for Syk in the development of
      gammadeltaT17. Syk induced the activation of the PI3K/Akt pathway upon
      gammadeltaTCR stimulation. Mice deficient in PI3K signaling exhibited a complete
      loss of gammadeltaT17, without impaired development of IFN-gamma-producing
      gammadeltaT cells. Moreover, gammadeltaT17-dependent skin inflammation was
      ameliorated in mice deficient in RhoH, an adaptor known to recruit Syk. Thus, we
      deciphered lineage-specific TCR signaling and identified the Syk/PI3K pathway as
      a critical determinant of proinflammatory gammadeltaT cell differentiation.

PMID- 29202477
TI  - CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2.
AB  - Pharmacologically difficult targets, such as MYC transcription factors, represent
      a major challenge in cancer therapy. For the childhood cancer neuroblastoma,
      amplification of the oncogene MYCN is associated with high-risk disease and poor
      prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified
      neuroblastoma and found a preferential dependency on genes encoding the polycomb
      repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and
      pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and
      in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN
      amplified neuroblastomas expressed higher levels of EZH2. ChIP analysis showed
      that MYCN binds at the EZH2 promoter, thereby directly driving expression.
      Transcriptomic and epigenetic analysis, as well as genetic rescue experiments,
      revealed that EZH2 represses neuronal differentiation in neuroblastoma in a PRC2
      dependent manner. Moreover, MYCN-amplified and high-risk primary tumors from
      patients with neuroblastoma exhibited strong repression of EZH2-regulated genes.
      Additionally, overexpression of IGFBP3, a direct EZH2 target, suppressed
      neuroblastoma growth in vitro and in vivo. We further observed strong synergy
      between histone deacetylase inhibitors and EZH2 inhibitors. Together, these
      observations demonstrate that MYCN upregulates EZH2, leading to inactivation of a
      tumor suppressor program in neuroblastoma, and support testing EZH2 inhibitors in
      patients with MYCN-amplified neuroblastoma.

PMID- 29202476
TI  - Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL
      11-JAK/STAT3 pathway.
AB  - Germline mutations in the gene encoding tumor suppressor kinase LKB1 lead to
      gastrointestinal tumorigenesis in Peutz-Jeghers syndrome (PJS) patients and mouse
      models; however, the cell types and signaling pathways underlying tumor formation
      are unknown. Here, we demonstrated that mesenchymal progenitor- or stromal
      fibroblast-specific deletion of Lkb1 results in fully penetrant polyposis in
      mice. Lineage tracing and immunohistochemical analyses revealed clonal expansion
      of Lkb1-deficient myofibroblast-like cell foci in the tumor stroma. Loss of Lkb1
      in stromal cells was associated with induction of an inflammatory program
      including IL-11 production and activation of the JAK/STAT3 pathway in tumor
      epithelia concomitant with proliferation. Importantly, treatment of LKB1-defcient
      mice with the JAK1/2 inhibitor ruxolitinib dramatically decreased polyposis.
      These data indicate that IL-11-mediated induction of JAK/STAT3 is critical in
      gastrointestinal tumorigenesis following Lkb1 mutations and suggest that
      targeting this pathway has therapeutic potential in Peutz-Jeghers syndrome.

PMID- 29202479
TI  - SPOP mutation drives prostate neoplasia without stabilizing oncogenic
      transcription factor ERG.
AB  - Nearly 50% of prostate cancers harbor gene fusions that lead to overexpression of
      the transcription factor ERG, while a mutually exclusive 10% of prostate cancers
      harbor recurrent mutations in the gene encoding the E3 ubiquitin ligase SPOP.
      Recent reports suggest that SPOP acts as a ubiquitin ligase for ERG and propose
      that ERG stabilization is the oncogenic effector of SPOP mutation. Here, we used
      human prostate cancer samples and showed that the vast majority of human SPOP
      mutant cancers do not express ERG. Comparison of SPOP-mutant and ERG-fusion
      organoid models showed evidence of divergent, rather than common, transcriptional
      programs. Furthermore, expression of prostate cancer-associated SPOP mutations in
      genetically engineered mouse models of SPOP-mutant prostate cancer did not result
      in the expression of ERG protein in histologically normal prostate glands, high
      grade prostatic intraepithelial neoplasia, invasive adenocarcinoma, or prostate
      organoids. In summary, we found no evidence that ERG is an effector of SPOP
      mutation in human prostate cancer or mouse models.

PMID- 29202480
TI  - Differential impact of RB status on E2F1 reprogramming in human cancer.
AB  - The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to
      suppression of transcription factor E2F1-mediated cell cycle regulation. For
      multiple tumor types, loss of RB function is associated with poor clinical
      outcome. RB action is abrogated either by direct depletion or through
      inactivation of RB function; however, the basis for this selectivity is unknown.
      Here, analysis of tumor samples and cell-free DNA from patients with advanced
      prostate cancer showed that direct RB loss was the preferred pathway of
      disruption in human disease. While RB loss was associated with lethal disease, RB
      deficient tumors had no proliferative advantage and exhibited downstream effects
      distinct from cell cycle control. Mechanistically, RB loss led to E2F1 cistrome
      expansion and different binding specificity, alterations distinct from those
      observed after functional RB inactivation. Additionally, identification of
      protumorigenic transcriptional networks specific to RB loss that were validated
      in clinical samples demonstrated the ability of RB loss to differentially
      reprogram E2F1 in human cancers. Together, these findings not only identify tumor
      suppressive functions of RB that are distinct from cell cycle control, but also
      demonstrate that the molecular consequence of RB loss is distinct from RB
      inactivation. Thus, these studies provide insight into how RB loss promotes
      disease progression, and identify new nodes for therapeutic intervention.

PMID- 29202481
TI  - Bone marrow drives central nervous system regeneration after radiation injury.
AB  - Nervous system injury is a frequent result of cancer therapy involving cranial
      irradiation, leaving patients with marked memory and other neurobehavioral
      disabilities. Here, we report an unanticipated link between bone marrow and brain
      in the setting of radiation injury. Specifically, we demonstrate that bone marrow
      derived monocytes and macrophages are essential for structural and functional
      repair mechanisms, including regeneration of cerebral white matter and
      improvement in neurocognitive function. Using a granulocyte-colony stimulating
      factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell
      transplantation, MRI, and neurocognitive functional assessments, we demonstrate
      that bone marrow-derived G-CSF-responsive cells home to the injured brain and are
      critical for altering neural progenitor cells and brain repair. Additionally,
      compared with untreated animals, animals that received G-CSF following radiation
      injury exhibited enhanced functional brain repair. Together, these results
      demonstrate that, in addition to its known role in defense and debris removal,
      the hematopoietic system provides critical regenerative drive to the brain that
      can be modulated by clinically available agents.

PMID- 29202482
TI  - Ligand-activated BMP signaling inhibits cell differentiation and death to promote
      melanoma.
AB  - Oncogenomic studies indicate that copy number variation (CNV) alters genes
      involved in tumor progression; however, identification of specific driver genes
      affected by CNV has been difficult, as these rearrangements are often contained
      in large chromosomal intervals among several bystander genes. Here, we addressed
      this problem and identified a CNV-targeted oncogene by performing comparative
      oncogenomics of human and zebrafish melanomas. We determined that the gene
      encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP
      family, is recurrently amplified and transcriptionally upregulated in melanoma.
      GDF6-induced BMP signaling maintained a trunk neural crest gene signature in
      melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF
      and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting
      cell death, and promoting tumor growth. GDF6 was specifically expressed in
      melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were
      inversely correlated with patient survival. Our study has identified a
      fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene
      signature to promote melanoma progression, thus providing potential opportunities
      for targeted therapy to treat GDF6-positive cancers.

PMID- 29202483
TI  - PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A
      features in rodent models.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of
      peripheral myelin protein 22 (PMP22) and is the most common hereditary peripheral
      neuropathy. CMT1A is characterized by demyelination and axonal loss, which
      underlie slowed motor nerve conduction velocity (MNCV) and reduced compound
      muscle action potentials (CMAP) in patients. There is currently no known
      treatment for this disease. Here, we show that antisense oligonucleotides (ASOs)
      effectively suppress PMP22 mRNA in affected nerves in 2 murine CMT1A models.
      Notably, initiation of ASO treatment after disease onset restored myelination,
      MNCV, and CMAP almost to levels seen in WT animals. In addition to disease
      associated gene expression networks that were restored with ASO treatment, we
      also identified potential disease biomarkers through transcriptomic profiling.
      Furthermore, we demonstrated that reduction of PMP22 mRNA in skin biopsies from
      ASO-treated rats is a suitable biomarker for evaluating target engagement in
      response to ASO therapy. These results support the use of ASOs as a potential
      treatment for CMT1A and elucidate potential disease and target engagement
      biomarkers for use in future clinical trials.

PMID- 29202484
TI  - Usefulness of the Martin Method for Estimation of Low-Density Lipoprotein
      Cholesterol in Coronary Atherosclerosis.
AB  - OBJECTIVE: This study was conducted to validate the Martin method in coronary
      atherosclerosis in comparison with the Friedewald equation. SUBJECTS AND METHODS:
      A total of 299 participants with a coronary artery calcium score (CACS) >=300 and
      a serum triglyceride (TG) level <400 mg/dL at Seoul National University Hospital
      Healthcare System Gangnam Center, Seoul, Korea, were enrolled in this study. Low
      density lipoprotein cholesterol (LDL-C) was directly measured with a homogeneous
      assay (DLDL) and estimated by both the Friedewald equation (FLDL) and Martin
      method (MLDL). Overall concordances between DLDL and LDL-C estimates were
      calculated as the percent agreement. The McNemar test was used to compare the
      rate of reclassification of participants with FLDL and MLDL, and to determine
      which differed significantly from each other. RESULTS: Overall concordance
      between DLDL and MLDL was slightly higher than that between DLDL and FLDL (73.2
      vs. 70.9%, p < 0.001). The FLDL showed poor performance when the TG level was
      >=200 mg/dL, mostly by underestimation, which represented a 64.7% discordance
      with DLDL. The reclassification rate by MLDL, however, did not exceed 35.3% in
      all of the TG groups. CONCLUSIONS: The Martin method to estimate LDL-C using the
      strata-specific TG:VLDL ratio showed a 2-fold better concordance with LDL-C
      measured with a direct homogeneous assay in coronary atherosclerosis compared to
      the Friedewald equation when the TG level was >=200 mg/dL. This finding suggests
      that MLDL could be a better alternative for estimating LDL-C compared to FLDL
      when the TG level is >=200 mg/dL in coronary atherosclerosis.

PMID- 29202485
TI  - Selenite restores Pax6 expression in neuronal cells of chronically arsenic
      exposed Golden Syrian hamsters.
AB  - Arsenic is a worldwide environmental pollutant that generates public health
      concerns. Various types of cancers and other diseases, including neurological
      disorders, have been associated with human consumption of arsenic in drinking
      water. At the molecular level, arsenic and its metabolites have the capacity to
      provoke genome instability, causing altered expression of genes. One such target
      of arsenic is the Pax6 gene that encodes a transcription factor in neuronal
      cells. The aim of this study was to evaluate the effect of two antioxidants,
      alpha-tocopheryl succinate (alpha-TOS) and sodium selenite, on Pax6 gene
      expression levels in the forebrain and cerebellum of Golden Syrian hamsters
      chronically exposed to arsenic in drinking water. Animals were divided into six
      groups. Using quantitative real-time reverse transcriptase (RT)-PCR analysis, we
      confirmed that arsenic downregulates Pax6 expression in nervous tissues by 53 +/-
      21% and 32 +/- 7% in the forebrain and cerebellum, respectively. In the presence
      of arsenic, treatment with alpha-TOS did not modify Pax6 expression in nervous
      tissues; however, sodium selenite completely restored Pax6 expression in the
      arsenic-exposed hamster forebrain, but not the cerebellum. Although our results
      suggest the use of selenite to restore the expression of a neuronal gene in
      arsenic-exposed animals, its use and efficacy in the human population require
      further studies.

PMID- 29202486
TI  - Vitamin D status in patients with rheumatoid arthritis: a correlation analysis
      with disease activity and progression, as well as serum IL-6 levels.
AB  - OBJECTIVES: Recent epidemiological studies suggested an association between a
      poor vitamin D [25(OH)D] status, inflammatory mediators, and rheumatoid arthritis
      (RA). We have recently proposed that pro-inflammatory interleukin 6 (IL-6) may
      represent a good marker for disease activity of RA. The aim of this study was to
      investigate the relationship between serum 25(OH)D levels and disease activity,
      joint damage, as well as serum IL-6 levels in a Polish RA population. MATERIALS
      AND METHODS: Serum 25(OH)D levels were measured in 35 female RA patients and 38
      age- and gender-matched healthy controls. Statistical correlations between
      25(OH)D levels and the disease activity score 28 (DAS 28), joint damage based on
      the Steinbrocker criteria, as well as serum IL-6 levels were performed. RESULTS:
      There was no statistically significant difference between levels of 25(OH)D in RA
      (16.89+/-8.57 ng/ml) and healthy controls (14.12+/-7.51 ng/ml), and the vitamin D
      deficiency (<20 ng/ml) was found in 71.43% of RA patients and 73.68 % of healthy
      controls. While vitamin D status did not correlate with DAS 28 (r=0.265, p=0.149)
      and joint damage based on the Steinbrocker criteria (r=0.367, p=0.065), a
      positive correlation between 25(OH)D and IL-6 (r=0.537, p=0.002) was observed in
      RA. CONCLUSION: Although further studies on a larger group of patients will be
      needed to confirm the data presented here, it seems that hypovitaminosis D is
      common in the RA patients and middle-aged non-RA healthy women in the Polish
      population. 25(OH)D levels were similar in the RA patients and age- and gender
      matched healthy controls, and were not associated with joint damage and disease
      activity in patients.

PMID- 29202487
TI  - Maillard neoglycans as inhibitors for in vitro adhesion of F4+ enterotoxigenic
      Escherichia coli to piglet intestinal cells.
AB  - Adhesion of enterotoxigenic (ETEC) E. coli to host intestinal cells is mediated
      by lectin-like fimbriae that bind to specific glycan moieties on the surfaces of
      enterocytes. To prevent in vitro binding of E. coli F4 fimbriae (F4 ETEC+) to
      piglet enterocytes, neoglycans were synthesized by the Maillard reaction
      conjugating lactose (Lac), galacto-oligosaccharides (GOS) or chitin
      oligosaccharides (Ochit) to porcine serum albumin (PSA). Neoglycans were
      characterized by SDS-PAGE, intrinsic tryptophan fluorescence and recognition by
      plant lectins, as well as by F4 ETEC variants. Electrophoretic patterns suggested
      the binding to PSA of 63, 13 and 2 molecules of Lac, GOS and Ochit, respectively.
      All neoglycans displayed quenching of tryptophan fluorescence consistent with the
      degree of glycation estimated by SDS-PAGE. Plant lectins recognized the
      neoglycans according to their specificity, whereas antigenic variants of F4 ETEC
      (ab, ac and ad) recognized PSA-Ochit and PSA-Lac with higher affinity than that
      for GOS. Neoglycans partially hindered the in vitro binding of F4+ ETEC to piglet
      enterocytes in a dose-dependent manner. The most effective blocking was observed
      with PSA-Lac that partially inhibited the adhesion of bacteria to enterocytes in
      a dose dependent manner, as quantified by flow cytometry. Increased production of
      the cytokines IL-6 and TNF-alpha was observed in response to F4+ ETEC infection
      of enterocytes and production was reduced in the presence of PSA-Ochit and PSA
      GOS. These results suggest that neoglycans synthesized by the Maillard reaction
      could be useful in the prophylaxis of diarrhea in piglets.

PMID- 29202488
TI  - Acute tadalafil administration increases plasma fatty acids without changes in
      the inflammatory response in healthy men.
AB  - PURPOSE: Tadalafil, the phosphodiesterase type 5 inhibitor (PDE5I), has been
      shown to reduce visceral adipose tissue in rabbit and to improve lean mass
      content in non-obese men. In order to clarify this effect in humans, in the
      present study we determined the impact of an acute oral tadalafil administration
      on lipolysis by evaluating plasma free fatty acids (FFAs) and glycerol. FFAs are
      potential modulator of inflammation response that we evaluated through tumor
      necrosis factor alpha (TNFalpha), interleukin 6 (IL6), interleukin 8 (IL8) and
      interleukin 10 (IL10) plasma levels. Moreover, we determined whether the effects
      of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two
      important molecules involved in PDE5Is signaling. METHODS: Twelve healthy
      subjects were supplemented with 20 mg of tadalafil or a placebo, in a double
      blind, randomized, cross-over design. Blood samples were collected immediately
      before, and at 2, 6, and 24 hours post ingestion, and assayed for biochemical
      analysis. RESULTS: A condition effect was noted for FFAs and glycerol, with
      values higher for tadalafil when compared to the placebo group, at 2 and 6 hours
      post ingestion. No statistically significant effects were noted for glucose,
      cGMP, nitrate and nitrite. No inflammatory response was induced by tadalafil.
      CONCLUSION: Tadalafil, in human subjects, increases lipolysis as evidenced by a
      significant increase in circulating FFAs and glycerol, without affecting the
      plasma cGMP and NO levels; noticeably, the increase in FFAs did not develop an
      inflammatory response. Further well-controlled studies are warranted to assess
      the impact of tadalafil administration on weight/fat loss.

PMID- 29202489
TI  - [Physician - Pharmacist Communication about Potentially Severe Drug
      Interactions].
AB  - INTRODUCTION:  Potentially serious drug interactions are often detected by
      pharmacists. In such cases fast communication with the General Practitioner (GP)
      is required. However, contacting physicians by telephone is often difficult. In a
      previous project a fax template was developed allowing fast communication of
      serious drug interactions to the GP. Utilization of the template and interactions
      detected were assessed in this observational study. METHODS:  All pharmacists and
      GP in the city of Bremen were informed about the template. Severity of drug
      interactions was rated by the ABDA classification system (from 1
      "contraindication" to 8: "no action recommended"). Participating pharmacists were
      asked to send an anonymized copy of every template. A descriptive analysis of the
      interactions, actions recommended by the pharmacists and physicians' reactions
      was performed. RESULTS:  123 faxes were sent to the Pharmacist's Association in
      Bremen by 23 pharmacies (1 - 25 fax/pharmacy). In 108/123 cases (severe)
      interactions were reported. In the remaining cases the interaction could not be
      verified (n = 7) or unintended double medication (n = 8) was detected. GP gave
      feedback in 69.4 % (n = 75). The GP followed the recommendations made by the
      pharmacist changing their original prescription, discontinuing medication and or
      monitoring patient's therapy followed the recommendations made by the pharmacist
      (n = 23). Beside that GP, chose another strategy (n = 15) or gave feedback that
      the interaction was known and issued the prescription as planned (31.5 %, n =
      34). Check back with the patient was rarely recommended (n = 3). DISCUSSION:  Fax
      templates seem to be an accepted instrument by pharmacists reporting serious drug
      interactions and able to improve medication safety. Different than intended,
      pharmacists used template for reporting less severe drug interactions. Attention
      has to be paid to the risk of over alerting, reporting which can lead to
      unintended neglect of urgent problems. Pharmacists should therefore be encouraged
      to report only serious drug interactions.

PMID- 29202490
TI  - [Metastasation of cutaneous squamous cell carcinoma in the ENT-Area].
AB  - OBJECTIVES: Our aim was to investigate the metastasis behavior and its prognostic
      Factor for Survival, with our clinical data. MATERIALS AND METHODS: This
      retrospective study included 29 Caucasians, with a squamous cell carcinoma of the
      skin in the head and neck region, at our tertiary clinic between 2004 and 2016.
      All Patients received a Tumorresection and Neckdissection. We used either
      Ultrasound or Computer-Tomography (conventional or PET-CT) for our preoperative
      Staging and the Follow-up. The Patients were classified according to metastatic
      behavior and the corresponding survival rates were determined. RESULTS: We found
      11 patients with cervical metastases, 4 patients with parotideal metastases, 5
      patients had Metastasis in both locations. In 9 patients a prophylactic neck
      dissection was performed. A loco regional tumor recurrence occurred in a total of
      24 % of the cases, these cases were all associated with cervical metastasis. The
      5-year survival rate in these cases was 71 %; in contrast, it was 100 % when
      parotideal metastasis alone occurred. In the group with prophylactic neck
      dissection, one case was diagnosed with occult metastases. CONCLUSIONS: Cervical
      metastasis is associated with a poorer prognosis compared to parotideal
      metastasis. The survival rate after surgical therapy and, if necessary,
      additional adjuvant radiotherapy is generally good (79 %). The role of
      prophylactic neck dissection in cN0 with corresponding risk factors, has not been
      conclusively clarified.

PMID- 29202491
TI  - Diagnosis and Treatment of Primary Aldosteronism in 2017: Did We Achieve Our
      Goals?

PMID- 29202492
TI  - Subtyping of Patients with Primary Aldosteronism: An Update.
AB  - Primary aldosteronism (PA) comprises two main subtypes: unilateral aldosteronism,
      mainly caused by aldosterone-producing adenoma; and bilateral adrenal
      hyperplasia. Establishing the correct subtype in patients with PA is
      indispensible for choice of treatment. In addition to established methods,
      alternative tests are evolving for subtyping. Computed tomography (CT) and
      adrenal venous sampling (AVS) are currently recommended in the guidelines for the
      diagnostic work-up of patients with PA. CT cannot be used as a stand-alone test
      for subtyping because of its limited accuracy but may be used in combination with
      other tests such as AVS or functional imaging. Nevertheless CT remains mandatory
      to exclude adrenocortical carcinoma. AVS provides the most accurate test to
      detect excessive secretion of aldosterone from an adrenal mass but has several
      practical limitations and disadvantages. Therefore, alternative non-invasive and
      patient-friendly methods are required to determine the need for adrenalectomy.
      Functional imaging with specific molecular positron emission tomographic ligands
      is a potential alternative method that may replace AVS for subclassifying
      patients with PA. The results of preliminary studies of 11C-metomidate are
      promising but ligands incorporating radionuclides with longer half-lives that
      selectively bind to CYP11B2 are needed. Steroid profiling provides another method
      for subtyping and selecting patients for adrenalectomy, but this technology is in
      its infancy and prospective outcome-based studies are required to determine if
      this technique may provide an alternative to AVS.

PMID- 29202493
TI  - Health-Related Quality of Life and Mental Health in Primary Aldosteronism: A
      Systematic Review.
AB  - The aim of this review was to determine the impact of primary aldosteronism on
      health-related quality of life (HRQoL) and mental health. We performed a
      systematic literature search up to July 2017 in six electronic databases. First,
      we screened the articles derived from this search based on title and abstract.
      Second, the selected studies were systematically reviewed and checked for our
      predefined inclusion criteria. The search yielded 753 articles, of which 15
      studies met our inclusion criteria. Untreated patients with primary aldosteronism
      showed an impaired physical and mental HRQoL as compared to the general
      population. Multiple domains of HRQoL were affected. This applied to patients
      with both an aldosterone-producing adenoma and bilateral adrenal hyperplasia.
      Adrenalectomy improves HRQoL. Conflicting results have been reported on the
      extent of this improvement, the improvement after initiation of medical
      treatment, and whether there is a difference in HRQoL after both treatments.
      Similarly, psychopathological symptoms of anxiety, demoralization, stress,
      depression and nervousness were more frequently reported in untreated patients
      with primary aldosteronism than in the general population and patients with
      hypertension. Also an impaired sleep quality has been reported. Improvement of
      these symptoms was observed after treatment with both adrenalectomy and
      mineralocorticoid receptor antagonists. This review shows that HRQoL is impaired
      and psychopathology is more frequently reported in patients with primary
      aldosteronism. This seems to be at least partly reversible after treatment but
      the extent of improvement remains unknown. To assess HRQoL in these patients more
      precisely a primary aldosteronism-specific HRQoL questionnaire is required.

PMID- 29202494
TI  - Aldosterone-Producing Cell Clusters in Normal and Pathological States.
AB  - Primary aldosteronism (PA) significantly increases the risk of cardiovascular
      complications, and early diagnosis and targeted treatment based on its
      pathophysiology is warranted. Next-generation sequencing (NGS) has revealed
      recurrent somatic mutations in aldosterone-driving genes in aldosterone-producing
      adenoma (APA). By applying CYP11B2 (aldosterone synthase) immunohistochemistry
      and NGS to adrenal glands from normal subjects and PA patients, we and others
      have shown that CYP11B2-positive cells make small clusters, termed aldosterone
      producing cell clusters (APCC), beneath the adrenal capsule, and that APCC harbor
      somatic mutations in genes mutated in APA. We have shown that APCC are increased
      in CT-negative PA adrenals, while others showed potential progression from APCC
      to micro APA through mutations. These results suggest that APCC are a key factor
      for understanding the origin of PA, and further investigation on the relation
      between APCC and PA is highly needed.

PMID- 29202495
TI  - Disordered CYP11B2 Expression in Primary Aldosteronism.
AB  - Primary aldosteronism is the most common type of secondary hypertension affecting
      6-10% of patients with primary hypertension. PA is mainly caused by unilateral
      hyperaldosteronism due to an aldosterone-producing adenoma, unilateral
      hyperplasia with or without micronodules or bilateral zona glomerulosa
      hyperplasias with or without macro or micronodules. The development of antibodies
      against the terminal enzyme of aldosterone biosynthesis (CYP11B2) has permitted
      the further characterization of normal adrenals and resected adrenals from
      patients with primary aldosteronism. Normal adrenals exhibit two different
      patterns of cellular expression of CYP11B2: young individuals display a
      relatively uniform expression of the enzyme throughout the zona glomerulosa while
      the adrenals of older individuals have dispersed CYP11B2-expressing cells but
      have more groups of cells called aldosterone-producing cell clusters (APCC). APAs
      exhibit different patterns of CYP11B2 staining that vary from uniform to
      homogeneous. There are also a proportion of cells within the APA that co-express
      different enzymes that are not normally co-expressed in normal individuals.
      Approximately 30% of patients with unilateral hyperaldosteronism do not have an
      APA, but either have an increased number of CYP11B2 expressing micronodules or
      hyperplasia of the zona glomerulosa. In summary, the studies reported in this
      review are shedding new light on the pathophysiology of primary aldosteronism.
      The wide variation in histopathological features of the adenomas and concurrent
      presence of APCCs raises the possibility that most cases of unilateral production
      of aldosterone actually might represent bilateral asymmetric hyperplasia with
      nodules frequently due to the development of somatic aldosterone-driving
      mutations.

PMID- 29202496
TI  - Primary Aldosteronism and Obstructive Sleep Apnea: Is This A Bidirectional
      Relationship?
AB  - It has been suggested that the high prevalence of obstructive sleep apnea (OSA)
      in resistant hypertension (RHT) may be related to the high prevalence of primary
      aldosteronism (PA) in patients with RHT. It has been also hypothesized that the
      relationship between aldosterone and OSA might be bidirectional. In patients with
      RHT, it has been shown that aldosterone levels correlate with severity of OSA and
      that blockade of aldosterone reduces the severity of OSA. It has been postulated
      that aldosterone worsens OSA by promoting accumulation of fluid, which shifted in
      the supine position to the neck, contributes to increased upper airway
      resistance. Also there is growing data that PA is more frequent in patients with
      OSA and that the treatment of PA positively influences OSA course. Also in some
      studies it has been shown that patients with OSA are characterized by higher
      aldosterone levels and higher prevalence of PA than patients without OSA and that
      causal treatment of OSA might decrease aldosterone levels. Moreover, the recent
      guideline of the Endocrine Society on management of PA recommends to screen
      hypertensive patients with OSA for PA.

PMID- 29202498
TI  - Antibiotic Awareness Week - November 2017: Veterinary Surgeons - Leaders in
      Antimicrobial Stewardship?

PMID- 29202499
TI  - Evaluation of Intra- and Inter-observer Measurement Variability of a Radiographic
      Stifle Osteoarthritis Scoring System in Dogs.
AB  - Objectives To evaluate the intra- and inter-observer measurement variability of
      an existing osteoarthritis (OA) stifle scoring system. Methods Paired
      caudocranial and mediolateral canine stifle radiographs were selected randomly. A
      total of 15 assessment points were evaluated independently and graded twice
      (integer numeric scale: 1-4) at an interval of 2 weeks by three observers with
      different levels of experience. The grades for each of the 15 factors were summed
      to obtain the OA score for each patient. Results The 15 independent assessment
      points measured by the three observers showed high reproducibility and low intra
      observer variability. Inter-observer variability was also low (mean: 1.09 +/-
      4.99, 95% CI [confidence interval]: -0.35 to 2.55). The most discordant ratings
      among the three observers involved sesamoid bones of gastrocnemius muscle
      (assessment point 11 of 15) and popliteal surface of femur (assessment point 10
      of 15). Clinical Significance A validated and feasible OA scoring method is
      prerequisite for reliable radiographic assessment of OA progression. The low
      overall inter- and intra-observer variabilities among the 15 independent measures
      of the OA scoring system presented herein support its feasibility for application
      in clinical practice as an objective tool for radiographic scoring of stifle OA.

PMID- 29202500
TI  - Evaluation of the Environmental Bias on Accelerometer-Measured Total Daily
      Activity Counts and Owner Survey Responses in Dogs with Osteoarthritis.
AB  - Objective To determine if environmental variables affect the average daily
      activity counts (AC) of dogs with osteoarthritis (OA) and/or owners' perception
      of their dog's clinical signs or quality of life. Methods The AC and Canine Brief
      Pain Inventory (CBPI) owner questionnaires of 62 dogs with OA were compared with
      daily environmental variables including the following: average temperature (
      degrees C), high temperature ( degrees C), low temperature ( degrees C), relative
      humidity (%), total precipitation (mm), average barometric pressure (hPa) and
      total daylight hours. Results Daily AC significantly correlated with average
      temperature and total daylight hours, but average temperature and total daylight
      hours accounted for less than 1% of variation in AC. No other significant
      relationships were found between daily AC and daily high temperature, low
      temperature, relative humidity, total precipitation or average barometric
      pressure. No statistical relationship was found between daily AC and the CBPI,
      nor between environmental variables and the CBPI. Canine Brief Pain Inventory
      scores for pain severity and pain interference decreased significantly over the
      test period. Clinical Significance The relationship between daily AC and average
      temperature and total daylight hours was significant, but unlikely to be
      clinically significant. Thus, environmental variables do not appear to have a
      clinically relevant bias on AC or owner CBPI questionnaires. The decrease over
      time in CBPI pain severity and pain interference values suggests owners
      completing the CBPI in this study were influenced by a caregiver placebo effect.

PMID- 29202501
TI  - Assessment of T2 Relaxation Times for Normal Canine Knee Articular Cartilage by
      T2 Mapping Using 1.5-T Magnetic Resonance Imaging.
AB  - Objectives This study aims to assess and compare the T2 relaxation times for
      articular cartilage of normal canine stifle joints in four regions by T2 mapping
      using a 1.5-T magnetic resonance imaging (MRI). Methods In vivo prospective
      study: 20 hindlimbs (left and right) from 10 normal healthy beagle dogs (n = 20).
      The region of interest (ROI) was subdivided into medial and lateral condyles of
      femoral cartilage (MF and LF, respectively) and medial and lateral condyles of
      tibial cartilage (MT and LT, respectively). The T2 relaxation times were assessed
      in regions where the cartilage thickness was greater than 0.5 mm. Results The
      median maximum cartilage thickness (mm) of the four ROI were 0.7 (range: 0.9
      0.6), 0.6 (range: 0.7-0.5), 0.7 (range: 0.9-0.5) and 0.6 (range: 0.8-0.5) at MF,
      LF, MT and LT, respectively. The errors in the measurement (%) of the four ROI
      were 64.3 (range: 50.0-75.0), 75.0 (range: 64.3-90.0), 64.3 (range: 20.0-90.0)
      and 75.0 (range: 56.3-90.0) at MF, LF, MT and LT, respectively. The median T2
      relaxation times (ms) for the articular cartilage of the four ROI were 70.2
      (range: 57.9-87.9), 57.5 (range: 46.8-66.9), 65.0 (range: 52.0-92.0) and 57.0
      (range: 49.0-66.2) at MF, LF, MT and LT, respectively. The inter-observer
      correlation coefficient (ICC, 2.1) for the T2 relaxation times of MF was 0.644.
      Clinical Significance This study offers useful information on T2 relaxation times
      for articular cartilage of the stifle joint using a 1.5-T MRI in normal dogs.

PMID- 29202502
TI  - Variation in the Quantity of Elastic Fibres with Degeneration in Canine Cranial
      Cruciate Ligaments from Labrador Retrievers.
AB  - Objectives This study aims to quantify numbers of elastic fibres in cranial
      cruciate ligaments from a dog breed at high risk of cranial cruciate ligament
      disease. Methods Macroscopically normal cranial cruciate ligaments were harvested
      from six Labrador retrievers. Sequential histological sections were assessed for
      extracellular matrix degeneration (haematoxylin and eosin stain) and elastic
      fibre staining (Miller's stain). Elastic fibres were semi-quantified using
      previously published scoring systems. Each section was scored twice by two
      observers. Results Increased numbers of elastic fibres were seen with increasing
      cranial cruciate ligament degeneration (p = 0.001). Labrador retriever cranial
      cruciate ligaments had lower elastic fibre staining when compared with previous
      published findings in the racing greyhound. Clinical Significance The cranial
      cruciate ligaments from a dog breed at high risk of cranial cruciate ligament
      disease vary in the quantity of elastic fibres in association with ligament
      degeneration. Breed variation in the quantity of elastic fibres may reflect
      differing risk of cranial cruciate ligament disease.

PMID- 29202503
TI  - Quantitative Analysis and Development of the Fore Feet of Arabian Foals from
      Birth to 1 Year of Age.
AB  - Objectives The goal of this study was to quantify external and internal
      anatomical characteristics of the foal foot throughout the first year of age.
      Methods Digital radiographs and photographs were taken bimonthly of the forefeet
      of nine Arabian foals, beginning at about 2 weeks of age until 12 months of age.
      Sixty-eight linear and angular variables were measured using NIH (National
      Institutes of Health) Image J software. Statistical analyses were performed using
      piecewise random coefficient model and p-values < 0.05 were considered
      significant. Results Distinct changes in hoof development were identified between
      4 and 8 months of age. Distinct changes were identified in several external
      (conformational) measurements including hoof solar widths and lengths, palmar
      heel lengths, toe and heel angles and in several internal (radiographic)
      measurements including the widths and lengths of the phalanges and sesamoid bones
      as well as joint angles. Clinical Significance Existing knowledge of distal limb
      development in foals, particularly the foot, is limited. These findings define
      the measurable changes of the foal foot as it grows during the first year of
      life. These data provide an insight into the transformation of the hoof from its
      initial oval to a circular shape and from a club-like, cylindrical conformation
      to a more angled, conical conformation. This paper quantifies this development,
      ultimately allowing a better understanding of morphological changes in the foot
      of the growing foal.

PMID- 29202504
TI  - Computed Tomographic Analysis of Ventral Atlantoaxial Optimal Safe Implantation
      Corridors in 27 Dogs.
AB  - Objectives Ventral atlantoaxial stabilization techniques are challenging surgical
      procedures in dogs. Available surgical guidelines are based upon subjective
      anatomical landmarks, and limited radiographic and computed tomographic data. The
      aims of this study were (1) to provide detailed anatomical descriptions of
      atlantoaxial optimal safe implantation corridors to generate objective
      recommendations for optimal implant placements and (2) to compare anatomical data
      obtained in non-affected Toy breed dogs, affected Toy breed dogs suffering from
      atlantoaxial instability and non-affected Beagle dogs. Methods Anatomical data
      were collected from a prospectively recruited population of 27 dogs using a
      previously validated method of optimal safe implantation corridor analysis using
      computed tomographic images. Results Optimal implant positions and three
      dimensional numerical data were generated successfully in all cases. Anatomical
      landmarks could be used to generate objective definitions of optimal insertion
      points which were applicable across all three groups. Overall the geometrical
      distribution of all implant sites was similar in all three groups with a few
      exceptions. Clinical Significance This study provides extensive anatomical data
      available to facilitate surgical planning of implant placement for atlantoaxial
      stabilization. Our data suggest that non-affected Toy breed dogs and non-affected
      Beagle dogs constitute reasonable research models to study atlantoaxial
      stabilization constructs.

PMID- 29202505
TI  - Incidence of Abnormalities of the Second and Third Cervical Vertebral Junction in
      Dogs with Atlantoaxial Instability: A Multicentre Study.
AB  - Objective To evaluate the occurrence and frequency of abnormalities at the second
      and third cervical vertebral junction (C2/3) in dogs with and without
      atlantoaxial instability (AAI). Study Design Retrospective multi-institutional
      case-controlled case series. Animals One hundred and seventeen dogs with AAI and
      117 dogs without AAI. Methods Radiographs, together with computer tomographic
      images or magnetic resonance images or both, of the cranial cervical spine of
      dogs were reviewed for the presence or absence of intervertebral disc-related
      anomalies, osseous fusion of the vertebrae, spondylosis, or any other anomaly of
      the C2/3. Results The incidence of anomalies affecting the C2/3 in dogs with AAI
      was 38.46% (n = 45) and in the control group it was 11.97% (n = 14). The majority
      of the observed anomalies involved the intervertebral disc. In conjunction with
      AAI, intervertebral disc-related anomalies were noted in 33.34%, spondylosis in
      2.56%, osseous fusion in 1.71% and a hypoplasia of the spinous process in 0.85%
      of the cases. Summarized under the term intervertebral disc-related anomalies, a
      morphological alteration of the intervertebral disc was noted in 10 cases with
      AAI, characterized by a spherical outer shape and a minimally reduced size and a
      dorsal positioning in the intervertebral space. Conclusion There is a
      significantly higher incidence of anomalies affecting the C2/3 in association
      with AAI. In conjunction with AAI, intervertebral disc-related anomalies are the
      most frequent pathological finding affecting the C2/3.

PMID- 29202506
TI  - Effect of Facetectomy on the Three-Dimensional Biomechanical Properties of the
      Fourth Canine Cervical Functional Spinal Unit: A Cadaveric Study.
AB  - Objective To study the biomechanical effect of facetectomy in 10 large breed dogs
      (>24 kg body weight) on the fourth canine cervical functional spinal unit.
      Methods Canine cervical spines were freed from all muscles. Spines were mounted
      on a six-degrees-of-freedom spine testing machine for three-dimensional motion
      analysis. Data were recorded with an optoelectronic motion analysis system. The
      range of motion was determined in all three primary motions as well as range of
      motion of coupled motions on the intact specimen, after unilateral and after
      bilateral facetectomy. Repeated-measures analysis of variance models were used to
      assess the changes of the biomechanical properties in the three treatment groups
      considered. Results Facetectomy increased range of motion of primary motions in
      all directions. Axial rotation was significantly influenced by facetectomy.
      Coupled motion was not influenced by facetectomy except for lateral bending with
      coupled motion axial rotation. The coupling factor (coupled motion/primary
      motion) decreased after facetectomy. Symmetry of motion was influenced by
      facetectomy in flexion-extension and axial rotation, but not in lateral bending.
      Clinical Significance Facet joints play a significant role in the stability of
      the cervical spine and act to maintain spatial integrity. Therefore, cervical
      spinal treatments requiring a facetectomy should be carefully planned and if an
      excessive increase in range of motion is expected, complications should be
      anticipated and reduced via spinal stabilization.

PMID- 29202507
TI  - Effect of Limb Position at the Time of Skin Marker Application on Sagittal Plane
      Kinematics of the Dog.
AB  - Objectives To evaluate the effect of limb position during initial skin marker
      application on sagittal plane kinematics of the hindlimb. Methods Six healthy
      dogs (20-30 kg) were evaluated. An established two-dimensional kinematic model of
      the pelvic limb was utilized to describe sagittal plane motion. Kinematic markers
      were applied separately for each dog while standing in three different positions:
      (1) the limb extended cranially, (2) a normal standing limb position and (3) the
      limb extended caudally. Following marker application at each of the three
      positions, dynamic gait was recorded at a walk (velocity, 0.9-1.2 m/s;
      acceleration, 0.5m/s2). Five valid trials were used for comparison. Complete
      waveform analysis was performed with generalized indicator function analysis
      (GIFA). Maximum and minimum joint angles and joint range of motion were compared
      with a one-way repeated measures ANOVA with significance at p < 0.05. Results
      Significant differences were found between stifle waveforms. No differences were
      found between the hip or tarsus waveforms. Minimum and maximum joint angles were
      significantly different for the hip and stifle but not for the tarsus. No
      differences were found between ranges of motion for any joint evaluated. Clinical
      Significance Limb position at the time of skin marker application affects gait
      data and is an important consideration for kinematic analysis of the hindlimb in
      dogs.

PMID- 29202508
TI  - Outcome of Repair of Distal Radial and Ulnar Fractures in Dogs Weighing 4 kg or
      Less Using a 1.5-mm Locking Adaption Plate or 2.0-mm Limited Contact Dynamic
      Compression Plate.
AB  - Objectives Retrospective evaluation of repairing distal radial and ulnar
      fractures in small breed dogs with the Synthes 1.5-mm locking Adaption plate
      system and compare results in a similar group of patients repaired with the
      Synthes 2.0-mm limited contact-dynamic compression plate (LC-DCP). Methods
      Electronic medical records from one specialty referral centre were reviewed from
      March 21, 2010, to October 9, 2015, for patients weighing less than or equal to 4
      kg that had a distal one-third radial and ulnar fracture repaired with a Synthes
      1.5-mm locking adaption plate or Synthes 2.0-mm LC-DCP. Further inclusion
      criteria included application of the plate to the cranial surface of the radius
      via open reduction and internal fixation. Results Six 1.5-mm Adaption plates and
      7 2.0-mm LC-DCPs were used to repair 13 distal radial and ulnar fractures in 12
      dogs. There were three major complications in the 1.5-mm adaption plate group
      (one plate fracture, one screw pull-out and one fracture through a distal screw
      hole) and one major complication in the 2.0-mm LC-DCP group due to a re-fracture.
      All patients without a complication had good or excellent functional outcome.
      Clinical Significance The authors recommend that the 1.5-mm Adaption plate be
      used only when a 2.0-mm LC-DCP would not allow for a minimum of two screws in the
      distal segment and at the discretion of the surgeon.

PMID- 29202509
TI  - Locking T-Plate Repair of Ilial Fractures in Cats and Small Dogs.
AB  - Objectives To assess screw loosening and pelvic narrowing following the use of
      locking implants to stabilise ilial body fractures in cats and small dogs.
      Methods Review of clinical records and post operative and follow up radiography
      of 12 cats and five small dogs to evaluate accuracy of fracture reduction, screw
      purchase and subsequent screw loosening and reduction in pelvic diameter. Results
      No screw loosening or reduction in pelvic diameter was observed at follow up.
      Clinical Significance Locking T-plates may prevent complications reported
      following the use of conventional implant systems for the repair of ilial
      fractures in cats and small dogs.

PMID- 29202510
TI  - Extraction Method and Analysis of Cannabinoids in Cannabis Olive Oil
      Preparations.
AB  - Recently, an increasing number of pharmacists had to supply medicinal products
      based on Cannabis sativa L. (Cannabaceae), prescribed by physicians to individual
      patients. Cannabis olive oil preparation is the first choice as a concentrated
      extract of cannabinoids, even though standardized operative conditions for
      obtaining it are still not available. In this work, the impact of temperature and
      extraction time on the concentration of active principles was studied to
      harmonize the different compounding methods, optimize the extraction process, and
      reduce the variability among preparations. Moreover, starting from the cannabis
      inflorescence, the effect of temperature on tetrahydrocannabinolic acid
      decarboxylation was evaluated. For the analysis, a GC/MS method, as suggested by
      the Italian Ministry of Health, and a GC/flame ionization detection method were
      developed, validated, and compared.

PMID- 29202512
TI  - A Simple and Rapid UPLC-PDA Method for Quality Control of Nardostachys jatamansi.
AB  - Nardostachys jatamansi is a well-documented herbal agent used to treat digestive
      and neuropsychiatric disorders in oriental medicinal systems. However, few
      simple, rapid, and comprehensive methods were reported for quality assessment and
      control of N. jatamansi. Herein, a UPLC with photodiode array detection method
      was developed for both fingerprint investigation of N. jatamansi and simultaneous
      quantitative analysis of the six serotonin transporter modulatory constituents in
      N. jatamansi. For chromatographic fingerprinting, 24 common peaks were selected
      as characteristic peaks to assess the consistency of N. jatamansi samples from
      different retail sources. Six of the common peaks (5, 7, 12: , and 16:  - 18: )
      were identified as desoxo-narchinol A, buddleoside, isonardosinone, nardosinone,
      kanshone H, and (-)-aristolone, respectively, by phytochemical investigation.
      Five of the six compounds significantly either enhanced or inhibited serotonin
      transporter activity, while (-)-aristolone (18: ) didn't show any serotonin
      transporter activity. In quantitative analysis, the six compounds showed good
      linearity (r > 0.999) within test ranges. The precision, expressed as relative
      standard deviation, was in the range of 0.25 - 2.77%, and the recovery of the
      method was in the range of 92 - 105%. The UPLC-photodiode array detection-based
      fingerprint analysis and quantitative methods reported here could be used for
      routine quality control of N. jatamansi.

PMID- 29202511
TI  - In Vitro Anti-inflammatory Effects of Equisetum arvense Are Not Solely Mediated
      by Silica.
AB  - Equisetum arvense, known as common horsetail, is used for the treatment of
      inflammatory diseases and is the plant with the highest concentration of silica.
      Yet it is unknown if the medicinal properties are mediated by its silica content.
      In the current study, optimal conditions for silica-rich horsetail preparations
      were identified. Bioactivity of the preparations was analyzed in vitro using flow
      cytometry-based activity and functionality profiling of primary human lymphocytes
      as well as cytokine measurement using a classical ELISA technique. Experiments
      revealed that horsetail preparations suppress activation and proliferation of
      lymphocytes by an interleukin-2-dependent mechanism. The effect increased with
      the silica concentration in the decoctions. Lymphocytes' polyfunctionality was
      also influenced, shown by a downregulation of IFN-gamma. Analytical profiling by
      HPLC-UV-MS and bioactivity testing revealed relevant immunosuppressive
      concentrations of a component that has been identified as isoquercitrin. Our
      results show that both silica and isoquercitrin are active compounds of horsetail
      preparations.

PMID- 29202513
TI  - New Pharmacological Opportunities for Betulinic Acid.
AB  - Betulinic acid is a naturally occurring pentacyclic lupane-type triterpenoid
      usually isolated from birch trees, but present in many other botanical sources.
      It is found in different plant organs, both as a free aglycon and as glycosyl
      derivatives. A wide range of pharmacological activities has been described for
      this triterpenoid, including antiviral and antitumor effects. In addition,
      several other interesting properties have been identified in the fields of
      immunity and metabolism, namely antidiabetic, antihyperlipidemic, and anti
      inflammatory activities. Taken together, these latter three properties make
      betulinic acid a highly interesting prospect for treating metabolic syndrome. The
      present review focuses on the therapeutic potential of this agent, along with
      several of its semisynthetic derivatives, which could open new frontiers in the
      use of natural product-based medicines.

PMID- 29202515
TI  - Recent Progresses in Breast Reconstruction: Stem Cells, Biomaterials, and Growth
      Factors.
AB  - Breast cancer is one of the most deadly tumors in women, and new procedures for
      post- surgical breast reconstruction have been developed which includes
      autologous stromal vascular fraction (SVF), platelet-derived growth factors,
      biomaterials and various stem cells. Adipose derived-stem cells (ASCs) has been
      reported to be one of the most widely used stem cell for breast reconstruction
      because of their ability to form new functional adipose tissue and vessels and in
      combination with stromal vascular fraction has been also reported efficient for
      breast reconstruction. Biomaterials include acellular dermal matrix, bone
      substitutes, and injectable have also been reported to be applicable for several
      clinical applications, including breast reconstruction surgery. Nevertheless,
      further studies are needed to explicitly define methodological procedures and to
      confirm the safety of all theses procedures during post-surgical breast
      reconstruction. The purpose of this mini-review is to summarize various recent
      and old applications of stem cells, biomaterials as well as growth factors in
      breast reconstruction.

PMID- 29202514
TI  - Glycyrrhetic Acid Derivative TY501 Protects Against Lithocholic Acid-Induced
      Cholestasis.
AB  - The aim of the study is to investigate the protective effects of TY501 against
      LCA-induced cholestasis in mice and to explore the potential mechanisms. It was
      demonstrated that TY501(5, 15 or 45 mg/kg, i.g.) can markedly reduced the level
      of ALT, AST and ALP which increased by LCA treatment. Meanwhile, TY501 also
      lowered total bile acids, total bilirubin and total cholesterol levels in serum.
      Furthermore, TY501 can protect HepG2 cell cultures from LCA-induced cytotoxicity.
      RT-PCR and Western Blot analysis showed that TY501 recovered the expression of
      BSEP, MRP2 and NTCP which were down-regulated by LCA. Moreover, mRNA and protein
      of FXR was also observed in TY501 treated mice significantly accumulation in
      nucleus. Taken together, It can be concluded that TY501 exerted beneficial
      effects on LCA-induced cholestasis, possibly via activation of FXR mediated
      upregulation of BSEP, MRP2 and NTCP.

PMID- 29202516
TI  - [Weighted gene co-expression network analysis in biomedicine research].
AB  - High-throughput biological technologies are now widely applied in biology and
      medicine, allowing scientists to monitor thousands of parameters simultaneously
      in a specific sample. However, it is still an enormous challenge to mine useful
      information from high-throughput data. The emergence of network biology provides
      deeper insights into complex bio-system and reveals the modularity in
      tissue/cellular networks. Correlation networks are increasingly used in
      bioinformatics applications. Weighted gene co-expression network analysis (WGCNA)
      tool can detect clusters of highly correlated genes. Therefore, we systematically
      reviewed the application of WGCNA in the study of disease diagnosis, pathogenesis
      and other related fields. First, we introduced principle, workflow, advantages
      and disadvantages of WGCNA. Second, we presented the application of WGCNA in
      disease, physiology, drug, evolution and genome annotation. Then, we indicated
      the application of WGCNA in newly developed high-throughput methods. We hope this
      review will help to promote the application of WGCNA in biomedicine research.

PMID- 29202517
TI  - [Advances in isoprene synthase research].
AB  - Isoprene emission can lead to significant consequence for atmospheric chemistry.
      In addition, isoprene is a chemical compound for various industrial applications.
      In the organisms, isoprene is produced by isoprene synthase that eliminates the
      pyrophosphate from the dimethylallyl diphosphate. As a key enzyme of isoprene
      formation, isoprene synthase plays an important role in the process of natural
      emission and artificial synthesis of isoprene. So far, isoprene synthase has been
      found in various plants. Isoprene synthases from different sources are of
      conservative structural and similar biochemical properties. In this review, the
      biochemical and structural characteristics of isoprene synthases from different
      sources were compared, the catalytic mechanism of isoprene synthase was
      discussed, and the perspective application of the enzyme in bioengineering was
      proposed.

PMID- 29202518
TI  - [Construction of high-yield strain by optimizing lycopene cyclase for beta
      carotene production].
AB  - To optimize key enzymes, such as to explore the gene resources and to modify the
      expression level, can maximize metabolic pathways of target products. beta
      carotene is a terpenoid compound with important application value. Lycopene
      cyclase (CrtY) is the key enzyme in beta-carotene biosynthesis pathway,
      catalyzing flavin adenine dinucleotide (FAD)-dependent cyclization reaction and
      beta-carotene synthesis from lycopene precursor. We optimized lycopene cyclase
      (CrtY) to improve the synthesis of beta-carotene and determined the effect of
      CrtY expression on metabolic pathways. Frist, we developed a beta-carotene
      synthesis module by coexpressing the lycopene beta-cyclase gene crtY with crtEBI
      module in Escherichia coli. Then we simultaneously optimized the ribosome-binding
      site (RBS) intensity and the species of crtY using oligo-linker mediated DNA
      assembly method (OLMA). Five strains with high beta-carotene production capacity
      were screened out from the OLMA library. The beta-carotene yields of these
      strains were up to 15.79-18.90 mg/g DCW (Dry cell weight), 65% higher than that
      of the original strain at shake flask level. The optimal strain CP12 was further
      identified and evaluated for beta-carotene production at 5 L fermentation level.
      After process optimization, the final beta-carotene yield could reach to 1.9 g/L.
      The results of RBS strength and metabolic intermediate analysis indicated that an
      appropriate expression level of CrtY could be beneficial for the function of the
      beta-carotene synthesis module. The results of this study provide important
      insight into the optimization of beta-carotene synthesis pathway in metabolic
      engineering.

PMID- 29202519
TI  - [Cloning, expression, purification and structure analysis of protein tyrosine
      phosphatase of Bombyx mori].
AB  - Protein tyrosine phosphatase (PTP, EC 3.1.3.48) specifically catalyzes the
      removal of phosphate groups from phosphorylated tyrosine residues, resulting in
      protein dephosphorylation, thus regulates life activities such as cell growth,
      proliferation, differentiation and immunization. Protein tyrosine phosphatase h
      of Bombyx mori (BmPTP-h) is involved in the replication of nucleopolyhedrovirus
      (NPV) in Bombyx mori, but the structure and properties of BmPTP-h are little
      known so far. In this study, the coding sequence of BmPTP-h gene was cloned from
      the midgut of Bombyx mori, and its genomic structure, mRNA structure, sequence
      signature, secondary structure and the state in solution were analyzed.
      Homologous amino acid sequences alignment analysis indicated that BmPTP-h had a
      high similarity to PTP sequences of numbers of insect NPVs, implying that they
      may have a common ancestor and similar function. We constructed a prokaryotic
      expression vector, expressed and obtained the soluble recombinant BmPTP-h in
      Escherichia coli at 25 C, and purified BmPTP-h using Ni-NTA affinity
      chromatography. Gel filtration analysis showed that BmPTP-h was able to form
      aggregate and monomer in solution. Circular dichroism spectroscopy analysis
      showed that the recombinant BmPTP-h contained alpha-helix structure. Increasing
      temperature resulted in the unfolding of the alpha-helix structure of BmPTP-h and
      the decrease of the alpha-helix structure content of BmPTP-h. These studies
      provide a basis to better study the structure and regulation mechanism of BmPTP
      h.

PMID- 29202520
TI  - [Expression and purification of rabies virus glycoprotein and analysis of its
      specific binding capacity to memory B cells].
AB  - We aimed to express and purify three rabies virus glycoproteins with different
      tags and sizes. After analyzing their binding function, we wish to obtain a
      rabies virus glycoprotein with higher affinity and ability to specifically bind
      memory B cells. Experiments were carried out to express full length, as well as
      the ectodomain RVG by gene engineering method. Combined with the antibody of CD19
      and CD27, the candidate protein labeling with fluorescence was used to analyze
      its binding function. Flow cytometry was used to detect the anti-rabies virus
      specific memory B cells in PBMCs, and confirm the binding ability between the
      candidate proteins and anti-rabies virus-specific memory B cells. We successfully
      constructed three expression vectors pGEX-5X-1-RVG, pET28a-RVG and pET30a-G.
      Three glycoproteins GST-RVG, His-RVG and His-G were obtained by optimized
      expression and purification conditions. The antigen specificity of purified GST
      RVG, His-RVG and His-G were identified by Western blotting and ELISA. The
      affinity of these three purified glycoproteins to anti-rabies virus antibody were
      detected by competitive ELISA. Anti-rabies virus specific memory B cells in
      positive PBMCs gained from people who had ever been injected with the vaccine can
      be detected by flow cytometry. Thus, we got a recombinant rabies virus
      glycoprotein that had high-affinity and could sort antigen specific memory B
      cells.

PMID- 29202521
TI  - [Effects of Astragalus polysaccharides on adipogenic differentiation of bone
      marrow mesenchymal stem cells in low oxygen environment].
AB  - To study the effect of Astragalus polysaccharide (APS) on adipogenic
      differentiation of bone marrow mesenchymal stem cells (BMSCs) cultured in hypoxic
      environment. The optimal APS concentration, which could promote the proliferation
      of BMSCs, was screened by methyl thiazolyl tetrazolium method. The concentration
      was used to intervene in BMSCs-induced by adipogenic differentiation fluid
      growing in different oxygen concentrations (3%, 6%, 10% and 20%). The formation
      of lipid droplets in the BMSCs-intervened was observed by oil red O staining
      under the optical microscope. The mRNA and protein levels of the lipid relating
      genes peroxisome proliferator activated receptor gamma 2 (PPAR-gamma2) and
      lipoprotein lipase (LPL) were detected by Real-time PCR and Western blotting,
      respectively. The results showed that, comparing with the control group, 40
      MUg/mL APS could significantly promote the proliferation of BMSCs under low
      oxygen concentration. A large amount of lipid droplets existed in BMSCs growing
      in the adipogenic inducing fluid containing 40 MUg/mL APS and the hypoxic
      environment, and the protein and mRNA levels of PPAR-gamma2 and LPL also raised.
      It was worth noting that the phenomenon was more significant in 10% oxygen
      concentration, and the difference was statistically significant (P<0.05). 40
      MUg/mL APS had effect on promoting the proliferation and adipogenic
      differentiation of BMSCs cultured in hypoxic environment, and the effect was
      related to the concentration of oxygen of BMSCs-cultured.

PMID- 29202522
TI  - [Establishment of dual reverse phase chromatography combined parallel reaction
      monitoring for targeted quantitative proteomics].
AB  - Steady improvement in mass spectrometers technology has transformed the targeted
      proteome analysis into a new stage. Parallel reaction monitoring (PRM) technology
      has evolved from the basic multiple reaction monitoring (MRM) targeted proteomics
      methods in recent years. PRM performs with a higher sensitivity, throughput and
      reproducibility in targeted quantification, however its limitations in
      effectiveness and accurate quantification of samples with higher complexity still
      remain unsolved. In this study through improving the chromatographic conditions
      of PRM we established a simple and robust platform for targeted proteomic
      quantification. The newly established PRM system is equipped with columns with
      increased inner diameter (150 MUm) and decreased total length (8 cm); faster
      liquid phase elution rate (800 nL/min) and shortened elution gradient (35 min).
      These modifications enable PRM platform to combine with dual reverse phase
      chromatography, to quantify up to 400 low abundance peptides in human 293T cells
      whole cell extract. Our findings would benefit the promotion of PRM technology,
      especially providing a technical option for accurate quantification of low
      abundance proteins.

PMID- 29202523
TI  - [Preparation of isotope dilution mass spectrometry standards based on glucose
      pulse].
AB  - Isotope Dilution Mass Spectrometry (IDMS) is the most accurate method for high
      throughput detection of intracellular metabolite concentrations, and the key is
      getting the corresponding fully uniformly(U) 13C-labeled metabolites to be
      measured. The conventional procedure for getting fully U 13C-labeled metabolites
      is through batch cultivation, but intracellular metabolites concentrations by
      this method are generally low. By applying U 13C-labeled glucose pulse, combined
      with fast sampling and quenching, mixture of fully U 13C-labeled intracellular
      metabolites was successfully extracted with higher concentration from Pichia
      pastoris G/DSEL fed with fully U 13C-labeled glucose as only carbon source.
      Quantitative results from liquid chromatography tandem mass spectrometry (LC-MS)
      and gas chromatography tandem mass spectrometry (GC-MS) show that concentrations
      of organic acids, sugar phosphates, amino acids and nucleotides were 2-10 folds
      higher than those without glucose pulse. Therefore, the glucose pulse method can
      efficiently improve the usage of fully U 13C-labeled glucose converting to 13C
      labeled metabolites, and achieve the detection of intracellular metabolites with
      lower concentrate than the instrument detection limit.

PMID- 29202524
TI  - [Effect of PTS modifications on L-tryptophan production in Escherichia coli].
AB  - L-tryptophan, one of the aromatic amino acids, is widely used in the fields of
      medicine, food and feed additives. The phosphoenolpyruvate-carbohydrate
      phosphotransferase system (PTS) plays an important role in glucose transport and
      phosphorylation in Escherichia coli. PTS-mediated regulation dominates the
      carbohydrates' uptake and metabolism in E. coli. We constructed L-tryptophan
      producing bacteria containing two typical PTS mutations (ptsHIcrrglf- glk+ and
      ptsG-) by Red homologous recombination system, and studied in 50 L jar fermenter
      using fed-batch fermentation. Both PTS system mutants had a great impact on the
      biomass (increasing 47.0% and 17.6%, respectively), L-tryptophan production
      (increasing 25.9% and 9.4%, respectively), glucose conversion rate (increasing
      26.5% and 17.4%, respectively) and byproduct acetic acid generation (slightly
      increased and decreased,respectively).

PMID- 29202525
TI  - [Establishment of kinetics digital model for hyaluronate lyase production based
      on fermentation optimization of Arthrobacter globiformis A152].
AB  - In order to produce hyaluronate lyase of high yield, we optimized the
      fermentation Arthrobacter globiformis A152 in quadruple fermentation of 5 L, and
      studied the kinetics of fermentation. Both the highest biomass and enzyme
      activity could be achieved when the rotation speed was 400 r/min and the
      ventilation volume was 3.5 L/min. In addition, digital models of cell growth,
      product synthesis and substrate consumption were built by equation of logistic,
      luedeking-piret, product synthesis and substrate consumption. Nonlinear fitting
      and estimation of optimal parameters were obtained by MATLAB. The model
      correlated well between prediction and experimental data, and reflected the
      change rules of cell growth, hyaluronidase synthesis and substrate consumption
      during the process of producing hyaluronate lyase. The establishment of
      fermentation kinetics digital models could provide basis for controlling and
      prediction of the production process.

PMID- 29202526
TI  - [Production of L-citrulline by a recombinant Corynebacterium crenatum SYPA 5-5
      whole-cell biocatalyst].
AB  - Arginine deiminase (ADI) was first high-efficient expressed in Corynebacterium
      crenatum SYPA 5-5. The ADI was purified by Ni-NTA affinity chromatography and SDS
      PAGE analysis showed the molecular weight (MW) was 46.8 kDa. The optimal
      temperature and pH of ADI were 37 C and 6.5 respectively. The Michaelis constant
      was 12.18 mmol/L and the maximum velocity was 0.36 MUmol/(min.mL). Under optimal
      conditions, 300 g/L of arginine was transformed and the productivity reach 8
      g/(L.h). The recombinant strain was cultivated in a 5-L fermentor and used for
      whole-cell transformation of 300 g/L arginine, under repeated-batch
      bioconversion, the cumulative production reached 1 900 g/L.

PMID- 29202527
TI  - [Right heart function:from backstage to front stage].

PMID- 29202528
TI  - [The treatment of chronic lymphocytic leukemia in the new medicine era].

PMID- 29202529
TI  - [Characteristics of cognitive function, behavioral and psychological symptoms in
      patients with Alzheimer's disease versus behavioral variant frontotemporal
      dementia].
AB  - Objective: To compare the differences in cognitive function and behavioral and
      psychological symptoms between patients with Alzheimer's disease (AD) and
      behavioral variant frontotemporal dementia (bvFTD). Methods: Thirty-six AD
      patients and 20 bvFTD patients at mild-to-moderate stage, who were biomarker
      confirmed by positron emission tomography (PET), were assessed with a
      neuropsychological battery and neuropsychiatry inventory (NPI). Cognitive
      domains, including memory, language, information processing speed and executive
      function, and behavioral and psychological symptoms were assessed and compared.
      Results: AD patients had lower scores in immediate recall, delayed recall and
      recognition than bvFTD patients (all P<0.05); while bvFTD patients had poorer
      performance in language and executive function than AD patients (all P<0.05). The
      NPI total score was significantly higher in patients with bvFTD compared with
      patients with AD (17.5+/-5.7 vs 9.3+/-3.5, P<0.05). In respect to the 12 items of
      NPI, the incidence of agitation and irritability was higher in AD group than in
      bvFTD group (72.2% vs 35.0%, 55.6% vs 20.0%, all P<0.05); while the incidence of
      apathy, disinhibition, euphoria, aberrant motor behavior and appetite/eating was
      higher in bvFTD group than in AD group (65.0% vs 33.3%, 80.0% vs 5.5%, 70.0% vs
      5.6%, 40.0% vs 11.1%, 50.0% vs 5.6%, all P<0.05). Conclusion: Comprehensive
      neuropsychological assessment and evaluation of behavioral and psychological
      symptoms of patients with dementia are helpful in distinguishing AD from bvFTD.

PMID- 29202530
TI  - [A comparison between the revision of Atlanta classification and determinant
      based classification in acute pancreatitis].
AB  - Objective: To compare the performance of the revision of Atlanta classification
      (RAC) and determinant-based classification (DBC) in acute pancreatitis. Methods:
      Consecutive patients with acute pancreatitis admitted to a single center from
      January 2001 to January 2015 were retrospectively analyzed. Patients were
      classified into mild, moderately severe and severe categories based on RAC and
      were simultaneously classified into mild, moderate, severe and critical grades
      according to DBC. Disease severity and clinical outcomes were compared between
      subgroups. The receiver operating curve (ROC) was used to compare the utility of
      RAC and DBC by calculating the area under curve (AUC). Results: Among 1 120
      patients enrolled, organ failure occurred in 343 patients (30.6%) and infected
      necrosis in 74 patients(6.6%). A total of 63 patients (5.6%) died. Statistically
      significant difference of disease severity and outcomes was observed between all
      the subgroups in RAC and DBC (P<0.001). The category of critical acute
      pancreatitis (with both persistent organ failure and infected necrosis) had the
      most severe clinical course and the highest mortality (19/31, 61.3%). DBC had a
      larger AUC (0.73, 95%CI 0.69-0.78) than RAC (0.68, 95%CI 0.65-0.73) in
      classifying ICU admissions (P=0.031), but both were similar in predicting
      mortality(P=0.372) and prolonged ICU stay (P=0.266). Conclusions: DBC and RAC
      perform comparably well in categorizing patients with acute pancreatitis
      regarding disease severity and clinical outcome. DBC is slightly better than RAC
      in predicting prolonged hospital stay. Persistent organ failure and infected
      necrosis are risk factors for poor prognosis and presence of both is associated
      with the most dismal outcome.

PMID- 29202531
TI  - [Clinical features of hospitalized patients with deep venous thrombosis].
AB  - Objective: To increase the consciousness of incident deep venous thrombosis (DVT)
      in hospitalized patients. Methods: This is a retrospective study of hospitalized
      patients with DVT in Beijing Shijitan Hospital from 2007 to 2016. Clinical
      features of DVT patients who were admitted with no DVT were summarized. The
      demographic and epidemiological characteristics, involved site of veins,
      department of patients and risk factors were discussed. Results: A total of 5 063
      patients were complicated with DVT from 305 922 inpatients who were without DVT
      at the admission during past 10 years. Among them, 54.36% (2 752/5 063) were men.
      The age of the patients was (74.1+/-15.9) years old (range 1-103 years) with
      37.78% of them in 80 to 89 age group. The incidence of DVT in the hospital was
      1.65%. It increased yearly during the past decade (from 0.50% to 2.74%), and
      increased with age in patients from 1 to 99 years old (7.32% in 90-99 age group).
      Totally, 5 204 veins were involved in the patients. Most thrombosis involved
      inferior vena cava system (96.54%,5 024/5 204), especially deep veins of lower
      extremity (83.78%,4 360/5 204), some involved portal veins (8.61%,448/5 204) and
      a little was found in superior venae cava (3.46%, 180/5 204). More DVT patients
      were in department of internal medicine than those in department of surgery
      (2.95% vs 0.97%, P<0.01). ICU had the highest rate of DVT among the hospital
      departments (9.75%). No DVT occurred in department of newborn. Risk factors of
      DVT were inflammatory diseases (71.54%), age over 75 years old (67.25%), and
      heart diseases (58.98%). Conclusion: Sensitivity of detection on DVT should be
      emphasized in hospitalized patients with DVT risk, especially at the department
      with high incident of DVT.

PMID- 29202532
TI  - [Premature outflow tract ventricular contraction combined with complete bundle
      branch block: the characteristic electrocardiographic and ablation target
      potential features].
AB  - Objective: To explore the characteristics of electrocardiogram(ECG) and target
      potential features of premature ventricular contraction (PVC) in patients with
      complete left/right bundle branch block (CL/RBBB) and compare with those without
      CL/RBBB. Methods: A retrospective analysis was done in 8 outflow tract PVC
      patients with CL/RBBB, who successfully underwent radiofrequency ablation from
      August 2009 to June 2017. According to the bundle branch block chamber, patients
      were divided into the complete right bundle branch block (CRBBB) group (n=4) and
      the complete left bundle branch block (CLBBB) group (n=4). The control group were
      those who successfully underwent ablation at the same position as the above two
      groups but without CL/RBBB. The characteristics of ECG and target potential
      features were compared among groups. Results: One case in the CRBBB group was
      successfully ablated in the great cardiac vein with precordial R/S>1 transition
      at V(1) and one case in the CLBBB group was successfully ablated in the right
      coronary cusp with precordial R/S>1 transition at V(2), while other 6 cases were
      all with precordial R/S>1 transition at lead V(4). Precordial R/S>1 transition
      was not later than sinus rhythm (SR) in the CLBBB group. No statistical
      difference was found in the QRS complex duration between SR and PVC in the
      CL/RBBB patients [(134.38+/-23.80)ms vs (156.75+/-25.93)ms, P>0.05], while
      statistical difference was shown in the control group [(92.63+/-5.76)ms vs
      (140.25+/-15.97)ms, P<0.05]. Conclusion: Bundle branch block can lead to
      misjudgment of PVC origin with CL/RBBB during sinus rhythm, thus the origin
      chamber of the PVC should be determined according to the mapping and ablation
      result.

PMID- 29202533
TI  - [The clinicopathological characteristics of diabetic nephropathy and non-diabetic
      renal diseases in diabetic patients].
AB  - Objective: To analyze the clinicopathological characteristics of renal lesions in
      type 2 diabetic patients and to differentiate diabetic nephropathy (DN) from non
      diabetic renal diseases(NDRD). Methods: Type 2 diabetic patients who received
      renal biopsy in Ruijin Hospital from January 2011 to December 2015 were recruited
      in this study. Clinical history, laboratory results and pathological data were
      retrospectively collected. According to the pathological findings, the patients
      were divided into 3 groups: DN, NDRD, DN+NDRD. Logistic model was applied to
      explore the independent clinical predictive factors in differentiating DN from
      NDRD. Results: A total of 207 type 2 diabetic patients received renal biopsy,
      accounting for 6.82% of all biopsy population. Fifty-one patients were diagnosed
      with DN, 142 with NDRD and 14 with both DN and NDRD. In NDRD, membranous
      nephropathy(MN)(34.5%) was the most common finding, followed by IgA
      nephropathy(19.7%).By contrast, NDRD patients manifested a shorter diabetic
      course, a higher baseline hemoglobin level, a lower baseline serum creatinine, a
      higher prevalence of hematuria, a lower prevalence of hypertension and diabetic
      retinopathy, a better control of blood glucose, better compliance of monitoring
      blood glucose and less family history of diabetes. In multivariate logistic
      model, diabetic family history(OR=4.68, P=0.04) and long history of
      diabetes(OR=1.01, P=0.02) were risk factors of DN. Conclusion: There is a high
      prevalence of NDRD in diabetic patients with renal lesions. Family history of
      diabetes and duration of diabetes are independent predictors of DN.

PMID- 29202534
TI  - [Investigation of doctors' and nurses' perceptions and implementation of delirium
      management in intensive care unit].
AB  - Objective: To investigate doctors' and nurses' perceptions and implementation of
      delirium management in intensive care unit. Methods: A total of 197 doctors and
      nurses in 2 general ICUs and 3 special ICUs at Peking Union Medical College
      Hospital finished a self-designed questionnaire of delirium management. Results:
      There were 47 males and 150 females, 43 doctors and 154 nurses who participated
      in the survey.One hundred and twenty five participators were from general ICU and
      the others from special ICU. The ICU staff had a significant difference on the
      perceptions and implementation of delirium management(P< 0.001) including.
      Doctors and nurses scored lowest in "family engagement and empowerment" and
      "sleep management" with (4.620+/-2.393) and (5.430+/-2.153) respectively. There
      was a significant difference between nurses and doctors in the management of
      analgesia and sedation (P< 0.05).Doctors and nurses from different ICUs had
      significant discrepancy in the implementation of "delirium assessment" (P< 0.05).
      Conclusions: The ICU staff should improve the perceptions and the implementation
      of delirium management,especially in special ICUs. Delirium management should be
      included as a routine care in ICU to improve patients' outcome.

PMID- 29202535
TI  - [The safety and efficacy of golimumab in treatment of 25 patients with active
      ankylosing spondylitis].
AB  - Objective: To evaluate the efficacy and safety of golimumab in patients with
      active ankylosing spondylitis (AS). Methods: This was a randomized, double-blind,
      placebo-controlled trial. The subjects were randomized to receive either
      golimumab 50mg subcutaneously or placebo every 4 weeks. Patients in both groups
      received golimumab 50mg from week 24 to week 48. The primary endpoint was the
      proportion of at least 20% improvement in the Assessment of Spondyloarthritis
      International Society (ASAS20) at week 14. The secondary endpoints included at
      least 40% improvement in the Assessment of Spondyloarthritis International
      Society (ASAS40), ASAS partial-remission, Bath AS functional index, Bath AS
      disease activity index, Bath AS metrology index, enthesitis index and Jenkins
      sleep evaluation questionnaire. Results: A total of 25 subjects were included in
      this study, 13 with golimumab and 12 with placebo. At Week 14, 6(46.2%) subjects
      achieved ASAS20 in golimumab group and 2(16.7%) in placebo group. Significant
      improvements of other efficacy endpoints were also found in golimumab group.
      Golimumab was safe and well to lerated. Most of the adverse events were slightly
      impaired liver function, where as elevated aspartate aminotransferase and/or
      alanine aminotransferase returned to normal without drug with drawal. Conclusion:
      Golimumab improves AS activity, clinical symptoms and sleep disturbance in
      patients with active AS with good safety and tolerability.

PMID- 29202537
TI  - [The clinicopathological characteristics and genetic analysis of a case of late
      onset glycogen storage disease type II caused by a novel deletion mutation].

PMID- 29202536
TI  - [A comparative study of using Brix meter versus ultrasonic monitoring of gastric
      residual volume in patients with enteral nutrition].
AB  - To investigate the accuracy and feasibility of Brix value on monitoring gastric
      residual volume (GRV) in patients with enteral nutrition. Fifty patients with
      enteral nutrition via nasogastric tube were enrolled. The GRV was measured by
      both ultrasonography and Brix value. The results were compared according to the
      methods. The Pearson correlation coefficients showed that GRV measured by these
      two ways was positively correlated (r=0.986, P<0.05). Moreover paired sample t
      test showed that the discrepancy was not statistically significant (P>0.05)
      between different measurements. The consistency was analyzed by Bland-Altman
      graph, showing that the two measurements were consistent. Brix value is
      recommended to measure GRV due to its convenience and easy operation.

PMID- 29202538
TI  - [Cyclical Cushing syndrome due to pulmonary neuroendocrine tumor: a case report].

PMID- 29202539
TI  - [The clinical implications of Todd's paralysis mimicking stroke].

PMID- 29202540
TI  - [Cardiac cephalgia].

PMID- 29202541
TI  - [Advances on mechanisms and application of granulocyte colony-stimulating factor
      in treatment of liver failure].

PMID- 29202542
TI  - [Advances in myositis-specific autoantibodies].

PMID- 29202543
TI  - [Experts consensus on the management of the right heart function in critically
      ill patients].
AB  - To establish the experts consensus on the right heart function management in
      critically ill patients. The panel of consensus was composed of 30 experts in
      critical care medicine who are all members of Critical Hemodynamic Therapy
      Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE
      (Grading of Recommendations Assessment, Development, and Evaluation) principle.
      Then the Delphi method was adopted by 52 experts to reassess all the statements.
      (1) Right heart function is prone to be affected in critically illness, which
      will result in a auto-exaggerated vicious cycle. (2) Right heart function
      management is a key step of the hemodynamic therapy in critically ill patients.
      (3) Fluid resuscitation means the process of fluid therapy through rapid
      adjustment of intravascular volume aiming to improve tissue perfusion. Reversed
      fluid resuscitation means reducing volume. (4) The right ventricle afterload
      should be taken into consideration when using stroke volume variation (SVV) or
      pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload
      alone could lead to septal displacement and damage the diastolic function of the
      left ventricle. (6) The Starling curve of the right ventricle is not the same as
      the one applied to the left ventricle,the judgement of the different states for
      the right ventricle is the key of volume management. (7) The alteration of right
      heart function has its own characteristics, volume assessment and adjustment is
      an important part of the treatment of right ventricular dysfunction (8) Right
      ventricular enlargement is the prerequisite for increased cardiac output during
      reversed fluid resuscitation; Nonetheless, right heart enlargement does not
      mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance
      induced by a variety of factors could affect right heart function by obstructing
      the blood flow. (10) When pulmonary hypertension was detected in clinical
      scenario, the differentiation of critical care-related pulmonary hypertension
      should be a priority. (11) Attention should be paid to the change of right heart
      function before and after implementation of mechanical ventilation and adjustment
      of ventilator parameter. (12) The pulmonary arterial pressure should be monitored
      timingly when dealing with critical care-related pulmonary hypertension
      accompanied with circulatory failure.(13) The elevation of pulmonary aterial
      pressure should be taken into account in critical patients with acute right heart
      dysfunction. (14) Prone position ventilation is an important measure to reduce
      pulmonary vascular resistance when treating acute respiratory distress syndrome
      patients accompanied with acute cor pulmonale. (15) Attention should be paid to
      right ventricle-pulmonary artery coupling during the management of right heart
      function. (16) Right ventricular diastolic function is more prone to be affected
      in critically ill patients, the application of critical ultrasound is more
      conducive to quantitative assessment of right ventricular diastolic function.
      (17) As one of the parameters to assess the filling pressure of right heart,
      central venous pressure can be used to assess right heart diastolic function.
      (18). The early and prominent manifestation of non-focal cardiac tamponade is
      right ventricular diastolic involvement, the elevated right atrial pressure
      should be noticed. (19) The effect of increased intrathoracic pressure on right
      heart diastolic function should be valued. (20) Ttricuspid annular plane systolic
      excursion (TAPSE) is an important parameter that reflects right ventricular
      systolic function, and it is recommended as a general indicator of critically ill
      patient. (21) Circulation management with right heart protection as the core
      strategy is the key point of the treatment of acute respiratory distress
      syndrome. (22) Right heart function involvement after cardiac surgery is very
      common and should be highly valued. (23) Right ventricular dysfunction should not
      be considered as a routine excuse for maintaining higher central venous pressure.
      (24) When left ventricular dilation, attention should be paid to the effect of
      left ventricle on right ventricular diastolic function. (25) The impact of left
      ventricular function should be excluded when the contractility of the right
      ventricle is decreased. (26) When the right heart load increases acutely, the
      shunt between the left and right heart should be monitored. (27) Attention should
      be paid to the increase of central venous pressure caused by right ventricular
      dysfunction and its influence on microcirculation blood flow. (28) When the
      vasoactive drugs was used to reduce the pressure of pulmonary circulation,
      different effects on pulmonary and systemic circulation should be evaluated. (29)
      Right atrial pressure is an important factor affecting venous return. Attention
      should be paid to the influence of the pressure composition of the right atrium
      on the venous return. (30) Attention should be paid to the role of the right
      ventricle in the acute pulmonary edema. (31) Monitoring the difference between
      the mean systemic filling pressure and the right atrial pressure is helpful to
      determine whether the infusion increases the venous return. (32) Venous return
      resistance is often considered to be a insignificant factor that affects venous
      return, but attention should be paid to the effect of the specific
      pathophysiological status, such as intrathoracic hypertension, intra-abdominal
      hypertension and so on. Consensus can promote right heart function management in
      critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

PMID- 29202545
TI  - MMP9 Gene Expression Variation by Ingesting Tart Cherry and P-Coumaric Acid
      During Remyelination in the Cuprizone Mouse Model.
AB  - Matrix metalloproteinase-9 (GELB) as a member of gelatinases plays key role in
      the destruction of blood-brain barrier (BBB), T cells migration into the CNS, and
      demyelination induction. Considering remyelination induction in response to tart
      cherry extract and pure p-coumaric acid ingestion via tracking MMP9 gene
      expression in the cuprizone mouse model. Firstly, predicting the chemical
      interaction between p-coumaric acid and MMP9 protein was conducted through PASS
      and Swiss dock web services. Next, the content of p-coumaric acid in the tart
      cherry extract was analyzed by HPLC. Later, mice (male, female) were categorized
      into two groups: standard, cuprizone. After the demyelination period, mice
      classified into four groups: standard, natural chow, tart cherry extract, p
      coumaric acid. Finally, brains were extracted from the skull, and MMP9 gene
      expression was evaluated by real time RT-PCR. Bioinformatics analysis displayed p
      coumaric acid has potent inhibitory effect on MMP9 gene expression (Pa=0.818)
      with estimated DeltaG (kcal/mol) -8.10. In addition, during the demyelination
      period, MMP9 expression was increased significantly in the male group that is
      related to myelin destruction. However, MMP9 was declined throughout
      remyelination in both male and female. It's remarkable that pure p-coumaric acid
      and tart cherry extract ingestion could decrease the gene expression ratio more
      than natural chow. According to the results, it's deduced the male mouse is more
      appropriate gender for demyelination induction via cuprizone. In addition, tart
      cherry extract and pure p-coumaric acid ingestion could decrease MMP9 gene
      expression level considerably during remyelination.

PMID- 29202544
TI  - [The 460th case: lower extremity edema, positive fecal occult blood].
AB  - An 61-year-old woman presenting deep vein thrombosis and persistent positive
      anticardiolipin antibodies was diagnosed as antiphospholipid syndrome and treated
      with low molecular weight heparin. Before and after anticoagulant therapy,
      continuous positive fecal occult-blood was found asymptomatically. Colonoscopy
      confirmed rectal cancer. Antiphospholipid autoantibodies are non-specially
      positive in some malignances, especially in elder onset patients. Thus, routine
      screening of malignancies is strongly suggested.

PMID- 29202546
TI  - Correlation of Minichromosome Maintenance Protein 6 Expression Rate and Clinical
      Outcome in Patients With Hodgkin's Lymphoma.
AB  - Minichromosome maintenance complex component 6 (MCM-6) is one of the six proteins
      of the MCM family, which are involved in the initiation of DNA replication,
      represents a marker of proliferating cells. The goal of this study was to
      evaluate the prognostic relevance of the neoplastic cell proliferation rate in
      patients with Hodgkin's lymphoma (HL). We evaluated the formalin-fixed paraffin
      embedded lymph node biopsy specimens from 55 patients by using monoclonal
      antibody against MCM-6 and compared these findings with clinical data and
      treatment outcome. Median of MCM-6 expression was 85% (range: 35%-99%). In
      multivariate analysis, MCM-6 expression, B symptoms, and age were not
      statistically significant predictor for relapse in contrary to response (P=.001)
      and stage of disease (P=.048). Patients with lower MCM-6 expression rates showed
      higher relapse rate and lower disease-free survival (DFS). Meanwhile, patients
      with MCM-6 expression less than 85% showed shorter DFS (P=.031). We hypothesize
      that in group of patients with lower MCM-6 expression rate, a larger proportion
      of proliferating malignant cells are arrested in the very early phase of mitosis,
      in comparison to the group of patients with higher MCM-6 expression, and this
      could imply a shorter and probably higher relapse rate in the former group.

PMID- 29202547
TI  - Predictors of Glycemic Response and Change in HbA1c Following Newly Initiated
      Basal Insulin Among Insulin Naive Adults With Type 2 Diabetes.
AB  - This sub-analysis of the Iran-AFECT study was to determine the baseline
      characteristics are predicting the likelihood of attainment of HbA1c goal and
      changing in HbA1c after initiation of basal insulin glargine in insulin naive
      people with type 2 diabetes not adequately controlled with oral glucose-lowering
      drugs. Iran-AFECT was a 24-week, prospective, multicenter, observational study of
      people with type 2 diabetes initiated or switched to insulin glargine. In this
      sub-analysis, we included all insulin naive people. Glycemic response was defined
      as HbA1c<=7.0% and/or change in HbA1c at week 24. Data on 433 participants were
      included. The mean HbA1c was 8.9%+/-0.9% at baseline which decreased to 7.6%+/
      1.2% (P<0.001). By week 24, 36% of the participants reached HbA1c<=7.0%. In
      univariate analysis, the strongest association was for the baseline HbA1c
      (r2=0.32, P<0.001). In multivariate analysis, predictors of change in HbA1c were
      baseline HbA1c (r2=0.29, P<0.001), and dosing of glargine (r2=0.01, P=0.02). The
      baseline HbA1c was accounting for 88% of explainable variances in HbA1c. The best
      cut-off predicting glycemic response for baseline HbA1c was 8.5%. Among factors
      predicting response to initiating basal insulin therapy with insulin glargine,
      baseline HbA1c is the strongest predictor explaining most of the variances in
      HbA1c change.

PMID- 29202548
TI  - Comparing the Levels of Acute-Phase Reactants Between Smoker and Nonsmoker
      Diabetic Patients: More Predicted Risk for Cardiovascular Diseases in Smoker
      Compared to Nonsmoker Diabetics.
AB  - Due to a close link between cardiovascular disorders and increased acute phase
      responses, it is now proposed the relation of total sialic acid (TSA) and C
      Reactive Protein (CRP) as main components of acute phase proteins and
      cardiovascular risk profiles such as diabetes mellitus and smoking. We
      hypothesized that the elevation in the level of TSA along with other prototype
      acute phase reactants such as CRP is expected more in the coexistence of diabetes
      and smoking than in diabetes mellitus alone. Ninety diabetic patients were
      randomly selected and entered into this case-control study. Using block
      randomization method, the patients were randomly assigned into smokers (n=45) and
      nonsmokers (n=45). A group of ten healthy individuals was also included as the
      control. The serum levels of TSA, CRP, iron, and hemoglobin were measured by the
      specific techniques. Comparing laboratory parameters across the three groups
      indicated significantly higher levels of TSA and CRP in smoker diabetics as
      compared to non-smoker diabetics and the healthy controls, while there was no
      difference in other parameters including serum iron and hemoglobin. A significant
      positive correlation was also revealed between TCA and CRP (r=0.324, P=0.030),
      but no significant association was found between other parameters. In the
      background of smoking, increasing the level of both TSA and CRP is predicted more
      than the existence of diabetes mellitus alone. In fact, the increase in these
      biomarkers is more predictable in smoker than in nonsmoker diabetics. This
      finding emphasizes the increased risk for cardiovascular disorders in smoker
      compared to non-smoker diabetics.

PMID- 29202549
TI  - Clonidine Sedation Effects in Children During Electroencephalography.
AB  - It is very important to have proper management in children with Seizure.
      Electroencephalography (EEG) as a diagnostic instrument has a key role in
      determining the management method of seizure in children. Because of poor
      cooperation of some children (especially children with attention deficit
      hyperactivity disorders and developmental disorders) in performing EEG, it is the
      best choice to sedate children before EEG. The aim of present study is to
      evaluate the sedation efficacy of clonidine in children before EEG. In a
      randomized clinical trial, 45 children age 2 to 12 with seizure, who referred to
      Children Hospital of Tabriz University of Medical Sciences and candidate for EEG,
      were studied. Sedation before EEG induced by 0.5 to 2.0 mg clonidine orally.
      Sedation score (0 to 5) measured by using eyes condition, response to voice, and
      response to touch. Successful sedation, EEG performing, and hemodynamic stability
      were evaluated during sedation. Of all patients, 40 patients (88.88%) were
      sedated successfully, and EEG was performed for all of the children. Mean onset
      time of clonidine effect was 35.47+/-13.56 minutes and mean time of that the
      patients' level of consciousness back to the level before administrating of
      clonidine was 77.55+/-26.87 minutes. Hemodynamic states of all patients were
      stable during the study, and there were no significant changes in vital sign of
      patients. In conclusion, clonidine can be considered as a safe alternative
      medication for sedation for EEG, which is fortunately associated with no
      significant change in vital signs, which may complicate overall status of
      patients.

PMID- 29202550
TI  - The Normal Value of Tibial Tubercle Trochlear Groove Distance in Patients With
      Normal Knee Examinations Using MRI.
AB  - Patellar instability is a multifactorial common knee pathology that has a high
      recurrence rate, and the symptoms continue and ultimately predispose the patient
      to chondromalacia and osteoarthritis. Tibial tuberosity-trochlear groove distance
      (TTTG) is very important in the assessment of patellofemoral joint instability.
      The purpose of this study was to report the normal value of TTTG in males and
      females in different age groups and to assess the reliability of MRI in measuring
      TTTG. All patients presenting with knee pain and normal examinations of the knee
      joint, with a normal MRI report, referring to Shahid Sadoughi hospital of Yazd,
      Iran, from April 2014 to September 2014, were included in the study. MR images
      were studied once by two radiologists and for the second time by one radiologist.
      Mean value of TTTG was reported for males and females and in three age groups.
      Intra- and inter-observer reliability was calculated. A total of 98 patients were
      eligible to evaluate during 6 months (68 male and 30 female). Mean TTTG was
      10.9+/-2.5 mm in total, which was 10.8+/-2.8 mm and 11.3+/-2.3 mm in males and
      females, respectively (P>0.05). Mean TTTG in males <=30 years, 30-50 years and,
      >=51-year-old were 10.8+/-2.6 mm, 10.8+/-2.7 mm, and 10.8+/-2.6 mm, respectively;
      that was 12.1+/-3.4 mm, 11.4+/-1.9 mm, and 10.5+/-1.7 mm in females <=30 years,
      31-50 years and, >=51-year-old, respectively (95% CI). The coefficient of
      variation was <10% for both intra- and interobserver analysis. The results of the
      present study showed no significant difference in TTTG value between males and
      females in different age groups. In addition, it demonstrated that MRI is a
      reliable method in assessment of TTTG and identified normal value for TTTG at
      10.9+/-2.5 mm.

PMID- 29202551
TI  - Off-Pump Versus On-Pump Coronary Artery Bypass Graft Surgery Outcomes During 6
      Years: A Prospective Cohort Study.
AB  - Given the ongoing controversy over the risks and benefits of on-pump versus off
      pump coronary artery bypass graft surgery (CABG), we aimed to compare time trends
      in off- and on-pump CABG long-term outcomes. In this prospective cohort study,
      the patients who underwent primary isolated non-emergent CABG in Imam Reza
      Hospital in Mashhad, Iran, in 2006 were followed for 6 years. The patients were
      contacted to obtain long-term follow-up data such as death, rehospitalization,
      myocardial infarction, and normal physical activity. The obtained data were
      analyzed in SPSS software (V: 16) using t-test, Fisher's Exact, chi-square, and
      Mann-Whitney tests, and relative risk. The significant level was set at
      P<0.05.The study included 61 patients of whom n=40 (65.6%) underwent off-pump
      CABG. The mean age of the patients was 59.0+/-11.31 years, and n=43 (70.5%) were
      men. No significant differences were found between the two groups in terms of
      outcomes during the 6 years (e.g., death, rehospitalization, myocardial
      infarction, and normal physical activity). There was 1 (5.0%) death, overall.
      Risk-adjusted death did not differ significantly between the off-pump and on-pump
      groups during the 6 years (RR, 0.952; 95% CI 0.866 to 1.048).According to the
      results, the outcomes were similar between off-pump and on-pump CABG in patients
      who underwent primary isolated non-emergent CABG during the 6-year follow-up
      phase.

PMID- 29202552
TI  - Another Novel Missense Mutation in ARSB Gene in Iran.
AB  - Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder
      caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB
      activities subsequently. This enzyme is essential for the breaking of
      glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB
      dysfunction results in imperfect breakdown of GAGs and their accumulation in
      urine. Mutations in ARSB gene are the main players in MPS-VI disease and its
      clinical consequences. Most reported mutations are point mutations but there are
      some other examples in literature. Here we report a novel missense mutation in
      ARSB gene that is inherited as an autosomal recessive mode and probably explain
      the clinical status of the proband. This mutation replaces the threonine 92 by
      proline and alters ARSB structure. This is the most feasible scenario for
      clinical condition we described here. This novel mutation should be remarked for
      PND and PGD to improve the health and management of such families.

PMID- 29202554
TI  - Bowen's Disease Associated With Two Human Papilloma Virus Types.
AB  - Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most
      Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized
      to the genital region or distal extremities (periungual sites) in which HPV type
      16 is frequently detected. Patient was a 64-year-old construction worker for whom
      we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical
      and medial knee. Biopsy established the diagnosis of Bowen's disease and
      polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was
      referred for surgical excision.

PMID- 29202553
TI  - Extramammary Paget's Disease Associated With Genital Wart and Lichen Sclerosus.
AB  - Extramammary Paget's disease is an uncommon intraepithelial adenocarcinoma in
      genital and perianal regions. Genital wart is the most common sexually
      transmitted disease caused by human papilloma viruses and vulval lichen sclerosus
      is chronic pruritic dermatitis in genital area which could be able to change to
      invasive squamous cell carcinoma. We report a patient who had simultaneous lichen
      sclerosus, genital wart and extramammary Paget's disease of the vulva. We could
      not find any significant association between them in literature.

PMID- 29202555
TI  - Drug-Induced by Systemic Lupus Erythematosus Presenting as Recurrent Pericardial
      Effusion After Mitral Valve Repair.
AB  - We report a patient presented with recurrent pericardial effusion caused by drug
      induced systemic lupus Erythematosus (SLE) following mitral valve repair. The
      surgery was complicated by hemiparesis and convulsion in early postoperative
      period. The patient had been received carbamazepine for a paroxysmal seizure that
      occurred following mitral valve repair. The post operative computed tomography
      showed embolic stroke and its sequel (seizure) that treated with carbamazepine.
      In the 3rd month of follow-up, however, hemiparesis recovered by physiotherapy
      but carbamazepine was not discontinued as by request of neurologist. In the 6th
      month of surgery, the patient admitted by dyspnea and massive pericardial
      effusion that treated by subxiphoid drainage. This event was re occurred in two
      times in a short time frame and each event treated by surgical approach. The
      serologic exam in the last admission revealed drug-induced lupus erythematosus.
      The carbamazepine as an anti convulsive drug has been described to cause LE like
      disease in multiple case reports. Laboratory exam exhibited the possibility of
      carbamazepine-induced lupus in our case, with the extremely rare presentation of
      recurrent massive pericardial effusion.

PMID- 29202556
TI  - A Rare Reason of Abnormal Uterine Bleeding.

PMID- 29202558
TI  - Malar region rejuvenation through non-invasive techniques: hyaluronic acid
      fillers and lipofilling.
AB  - Contour enhancements of the midface make up a dominant aspect of aesthetic
      surgery. The goal of midface rejuvenation is to decrease the prominence of
      grooves and creases as well as to provide volume to atrophied tissue. There are
      various options, including autologous tissue grafts, allogenic tissue grafts and
      alloplastic materials. In turn, patients? needs have led to an increasing trend
      of less invasive treatments. In the present study, 82 implants were used for
      midface augmentation in 41 patients (38 women, 3 men) between January 2014 and
      January 2016. Twenty-five patients were treated with Hyaluronic acid implants
      while the remaining 16 patients were treated with lipofilling. For both groups
      and in all cases, good integration of the filled material was observed in the
      malar region, with no significant treatment complications and the last follow-up
      visit demonstrated good results and overall satisfaction. Hyaluronic acid fillers
      and lipofilling are therefore the ideal answer to patients who aim for a natural
      and immediate result with manageable complications, but, unlike Hyaluronic acid,
      autologous fat allows us to obtain a long-lasting effect over time, resulting the
      closest thing to an ideal facial filler.

PMID- 29202559
TI  - Hyaluronan: an overview.
AB  - Hyaluronic acid (HA) is a polyanionic natural polymer occurring as a linear
      polysaccharide composed of glucuronic acid and N-acetylglucosamine repeats.
      Hyaluronic acid has a wide range of applications with its excellent
      physicochemical properties such as biodegradability, biocompatibility, non
      toxicity, non-immunogenicity and serves as an excellent tool in biomedical
      applications such as osteoarthritis surgery, ocular surgery, plastic surgery,
      tissue engineering and drug delivery. This work provides an overview on
      hyaluronic acid, its chemistry and biochemistry and its medical applications.

PMID- 29202557
TI  - Non-alcoholic fatty liver disease and lifestyle modifications, focusing on
      physical activity.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease, and the prevalence of non-alcoholic steatohepatitis (NASH) with fibrosis
      is increasing as the population with NAFLD ages. To date, lifestyle modifications
      including weight loss, increased physical activity, and dietary changes remain
      the treatment of choice for NAFLD because there are no approved effective
      pharmacologic agents. Increased physical activity has therapeutic effects on
      NAFLD by reducing hepatic fat independent of weight reduction. Indeed, even
      minimal physical activity below the recommended threshold may have a beneficial
      impact on NAFLD. Aerobic activity and resistance training have similar effects on
      NAFLD. Universal recommendations for the optimal intensity and dose of physical
      activity have not been established. Therefore, physical activity should be
      tailored based on a patient's clinical characteristics, comorbidities, and
      fitness capacity. Physical activity also prevents the development of NAFLD and
      may represent a valuable strategy for reducing the public health burden. However,
      there are insufficient data supporting the effects of physical activity on the
      progression of non-alcoholic fatty liver to NASH with advanced fibrosis, and on
      extrahepatic disease-related morbidity and mortality. In this paper, we review
      the role of physical activity in the management of NAFLD.

PMID- 29202560
TI  - The use of hyaluronic acid in the treatment of shoulder capsulitis: a systematic
      review.
AB  - Adhesive capsulitis (AC) is a common pathological condition of the shoulder
      characterized by painful restriction of range of motion (ROM) of the glenohumeral
      joint. Currently, no consensus has been reached regarding the best treatment.
      Hyaluronic acid (HA) injection is a safe procedure that can result in significant
      improvement in active and passive ROM, alleviating pain and improving shoulder
      function. We systematically reviewed current literature in order to evaluate the
      best evidence about the effectiveness of intra-articular HA injection for the
      treatment of primary AC. We searched Medline, CINAHL, Embase, Google Scholar and
      Cochrane Library. We selected studies comparing clinical outcomes of patients
      treated with HA in association or not with conventional therapy. Seven studies
      were evaluated: 2 uncontrolled randomized studies and 5 prospective randomized
      clinical trials with level of evidence I. Clinical outcome measures used
      included, among other, ROM, Visual Analogic Scale (VAS) pain scores, Constant
      score, Activity of daily living, Shoulder Pain and Disability Index (SPADI),
      American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopedic Association
      Score (JOA score). Improvement was noted in terms of ROM, constant scores and
      pain in patients affected by AC treated with intra-articular HA injections. When
      compared with cortisone intra-articular injection, HA has equivalent clinical
      outcomes and ROM. The heterogeneity of treatments used in the studies reviewed,
      makes it difficult to draw a definite conclusion on the subject. HA injections do
      not seem to determine the final outcomes directly compared with conventional
      treatments. However, they could play an important role for early mobilization in
      the initial stages, during which, due to pain and inflammation, the patient keeps
      the shoulder immobilized for a long time, determining the direct cause of AC.
      Numerous variables, including use of lidocaine, different HA and AC stages, could
      influence the results and deserve to be accounted for in future investigations.

PMID- 29202561
TI  - Meniscal extrusion as booster of osteoarthritis.
AB  - Meniscal extrusion (ME) has shown to play a critical but still unclear role in
      osteoarthritis (OA) development. ME has been described as an important risk
      factor in the progression of knee OA, as it is involved in the thinning of
      articular cartilage, joint space narrowing, spontaneous osteonecrosis of the knee
      and subchondral bone marrow lesions. Meniscal damage of any degree of severity
      could cause ME in both compartments, but it is commonly associated with severe
      meniscal tears or root tears mainly in the medial meniscus. Magnetic resonance
      imaging is the most commonly used imaging modality in the assessment of ME, while
      ultrasonography may represent a valid alternative with high sensitivity and
      specificity. Conservative treatment for ME includes physical therapy and
      rehabilitation to maintain range of motion, corticosteroid injections and intra
      articular injections of hyaluronic acid to provide short-term relief of knee
      pain. The goal of this study is to review standards of current diagnosis and
      treatment of ME and its relationship to knee OA.

PMID- 29202562
TI  - Intrarticular injections of hyaluronic acid for trapezio-metacarpal
      osteoarthritis: a systematic review.
AB  - Osteoarthritis (OA) of the base of the thumb, also known as Trapezio-Metacarpal
      (TM) OA, is a disabling condition, which mainly affects women and manual workers.
      When TM OA is not adequately treated, patients develop deformity and loss of
      function of the thumb. The surgical approach is a widespread strategy to treat
      this condition, but there is still no consensus on the most effective procedure.
      Therefore, several conservative strategies are commonly used, such as
      nonsteroidal anti-inflammatory drugs (NSAIDs) administration, thumb strengthening
      exercise, splinting, steroid (CS) and hyaluronic acid (HA) intrarticular
      injections. The present review of the literature aims to summarize the available
      scientific evidence on the treatment of TM OA with injections of HA. Thirteen
      studies were included: 7 randomized controlled trials, 5 case series and a case
      control study. Among these, 5 studies compared HA versus CS injection. Results
      from most of them reported better outcomes with HA injections in terms of
      function (strength) and joint motion, while CS injections had greater effect on
      pain; moreover, CS action was faster but shorter, while HA required more time to
      obtain a therapeutic benefit and lasted longer. In non-comparative articles, this
      trend was also confirmed. Indeed, the authors reported an improvement in pain
      relief up to six months. Similarly, all studies indicated hand function
      improvement over time, measured though DASH score, pincher and grip strength
      tests. Available data from included studies show that there is no clear evidence
      to suggest a treatment with HA injections as the best advisable non-operative
      treatment for TM OA. However, promising potentials were shown by the randomized
      controlled trials, suggesting that there is some benefit and less comorbidities
      with the administration of HA. Further research, such as trials evaluating larger
      cohorts with validated scores for long-term follow-up, is still necessary.

PMID- 29202563
TI  - Topical hyaluronic acid in rhinitis medicamentosa: could our perspective be
      changed?
AB  - This study was designed to prospectively evaluate the role of nebulized
      hyaluronic acid (HA) administered for 10 days as treatment for patients with
      rhinitis medicamentosa (RM). RM is a pathological condition of the nasal mucosa
      induced by prolonged, excessive or improper use of topical decongestants. It is
      characterized by persistent nasal congestion that can lead the patient to
      increase the frequency of application and the quantity of the substance being
      applied, resulting in dependence on topical nasal decongestants. Twenty-five
      patients were treated with HA nebulized via Spray-sol twice a day for 10-days
      (T1) (HA Spray-sol treatment group). Subsequently, after 3 days of washout,
      patients were treated with physiological saline nebulized via Spray-sol twice a
      day for 10 days. (T2) (saline Spray-sol treatment group). The HA Spray-sol
      treatment group (tp) significantly improved visual analogue scale (VAS) scores
      (T0=6.25+/-1.64 vs T1=3.91+/-1.30; p less than 0.05), whereas there was no
      statistically significant difference in the saline Spray-sol treatment group (tp)
      (p>0.05), results confirmed by the anterior active rhinomanometry (AAR) data (HA
      Spray-sol tp T0=1.193+/-0.83 vs T1=0.44+/-0.25, p less than 0.05; saline Spray
      sol tp (p>0.05). An improvement in the Global Rhinitis Score (GRS) was recorded
      in both groups (T0=15.37+/-5.16 vs T1=5.54+/-3.23, p less than 0.05; saline Spray
      sol tp T0=15.37+/-5.16 vs T2=10. 7+/-5.43; p less than 0.05). Both groups showed
      a significant reduction in mucosal oedema and nasal secretions. Patients treated
      with HA Spray-sol reduced or even eliminated (11/25 patients) the use of topical
      decongestant within 10 days of treatment with HA. The results of this study
      suggest nebulized topical 9-mg sodium hyaluronate plays a pivotal role in the
      management of RM.

PMID- 29202564
TI  - Systematic review: the efficacy of topical hyaluronic acid on oral ulcers.
AB  - The management of oral ulcers is a challenge for clinicians. Whilst there is
      widespread use of topical corticosteroids, antibiotics and antimicrobial, there
      is only weak evidence for the effectiveness of any of the topical treatments.
      Hyaluronic Acid (HA) has been recently proposed for topical administration in the
      treatment of oral ulcers and other painful oral lesions. The aim of the study is
      to systematically review the published literature regarding all the therapeutic
      effects of HA on painful oral lesions such as oral ulcers and oral lichen planus.
      Relevant published studies were found in PubMed, Google Scholar and Ovid using a
      combined keyword search or medical subject headings. At the end of our study
      selection process, 4 relevant publications were included: two regarding oral
      lichen planus, one Behcet?s Disease and Recurrent Aphthous ulcer and one in oral
      ulcers in general. Both subjective parameters such as healing period, VAS for
      pain and objective assessments such as number of ulcers, maximal area of ulcer
      and inflammatory signs, significantly improved after HA treatment. These data
      allow us to suggest that HA may play a pivotal role in the treatment of oral
      ulcers.

PMID- 29202565
TI  - The efficacy of topical hyaluronan in rhinosinusitis: a systematic review.
AB  - Rhinosinusitis is one of the most common inflammatory conditions of the nasal
      cavity and paranasal sinuses and is one of the most common causes of absence from
      work and for visits to the family doctor. The treatment strategy in both acute
      rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) is to reduce the severity
      of the symptoms, minimize the duration of the disease and prevent complications.
      Topical therapy has become an important tool in otolaryngologists? armamentarium
      for rhinosinusitis treatment. Recently, topical hyaluronic acid (HA), the major
      component of many extracellular matrices that promotes tissue healing, including
      activation and moderation of the inflammatory responses, cell proliferation,
      migration and angiogenesis, has been proposed for ARS and CRS adjuvant tool. The
      aim of the study is to systematically review the published literature regarding
      all the therapeutic effects of HA on the ARS and CRS. Relevant published studies
      were found in PubMed, Google Scholar and Ovid, using a combined keyword search or
      medical subject headings. At the end of our study selection process, 5 relevant
      publications were included: 2 of them investigated the potential role of HA in
      reducing symptoms and preventing exacerbations of CRS in adult population, two of
      them in paediatric patients affected by upper respiratory tract infections and
      one of them in cystic fibrosis patients with bacterial rhinopharyngitis. Data
      deriving from the present review of 5 clinical studies showed that the use of
      topical HA represents a relevant therapeutic advance in rhinosinusitis to
      minimize symptoms and prevent reacutization with a significant improvement of
      their quality of life, as it avoids systemic side effects and increases local
      drug activity. Further studies on larger populations and with new specific
      nebulization devices for upper airway are needed to confirm these encouraging
      results.

PMID- 29202566
TI  - Post-operative nebulized sodium hyaluronate versus spray after functional
      endoscopic sinus surgery for chronic rhinosinusitis.
AB  - We prospectively evaluated the efficacy of nebulized Hyaluronic Acid (HA) as an
      adjuvant treatment to hasten the improvement of nasal respiration and to minimize
      patients? discomfort in the postoperative functional endoscopic sinus surgery
      (FESS) for chronic rhino-sinusitis (CRS). We enrolled 33 CRS adult patients who
      underwent endoscopic functional sinus surgery. They were randomly assigned into
      two groups: Spray-Sol group (18 patients) with HA nebulized with a new nasal
      device named Spray-Sol and Spray group (15 patients) with a HA nebulized with a
      common spray. Both groups were treated twice daily for 4 weeks. CRS
      questionnaire, Visual analogic scale (VAS) and nasal endoscopy were used to
      assess the outcomes of the treatments during the 1st month of follow up. The mean
      VAS score of the Spray-Sol group at 2 weeks was significantly lower than the
      Spray group (5.2+/-2.1 vs 10.5+/-3.7; p less than 0.05). The VAS score remained
      significantly lower in the Spray-Sol group also at the 4 weeks (2.9+/-0.8 vs
      6.1+/-3.4; p less than 0.05). The CRS score was significantly better at week 2
      and 4 in both groups in comparison with baseline values, with better results in
      the Spray-Sol group. Since the first visit the Spray-Sol group also showed
      significantly lower crusts, edema and secretions than the Spray group (p less
      than 0.05). The compliance to treatment was similar in both groups. The results
      of this prospective study suggest a role nebulized of HA through new device
      (Spray-sol) as a supportive treatment for faster improvement of nasal
      respiration, also minimizing patient discomfort, promoting nasal mucosa healing
      in postoperative FESS for CRS.

PMID- 29202567
TI  - The use of hyaluronic acid in the treatment of ankle osteoarthritis: a review of
      the evidence.
AB  - Ankle osteoarthritis (OA) is a progressive degenerative joint disease that causes
      ankle pain and functional limitation especially during walking. It tends to
      involve younger people with high functional request and has often a post
      traumatic origin. Symptoms control through conservative treatment is essential to
      procrastinate as long as possible the need for surgery. Although few data are
      present in literature about the use of local viscosupplementation in ankle OA,
      their potential use for ankle OA has been suggested. We systematically reviewed
      literature to evaluate the best evidence about short and long term effectiveness
      of intra-articular HA injections in the treatment of ankle OA. After having
      screened titles and abstracts from PubMed, Ovid, Cochrane Reviews, Google
      Scholar, we identified 14 full text articles and collected the outcome rates of
      intra-articular cycles of HA injections in patients with symptomatic ankle OA.
      Only 4 randomized control trials were included. Ankle Osteoarthritis Scales
      (AOS), American Orthopedic Foot, Ankle Society (AOFAS) clinical rating score,
      visual analog scales (VAS), Western Ontario and McMaster Universities (WOMAC) OA
      Index of Pain, Stiffness, and Physical Function Score were most frequently used
      to evaluate outcomes. Although randomized trials showed scores improvement also
      in placebo-treated patients, current evidence suggests that viscosupplementation
      for treatment of ankle OA is a safe and effective method. More randomized
      controlled trials with a large number of patients that compare not only the
      different types, dosages and frequency of HA injections, but also the
      effectiveness of HA versus corticosteroids infiltrations and HA versus other
      types of conservative treatment are still needed.

PMID- 29202568
TI  - Hybrid hyaluronic acid versus high molecular weight hyaluronic acid for the
      treatment of osteoarthritis in obese patients.
AB  - Osteoarthritis (OA) of the knee is one of the most relevant and debilitating
      health problems. Obesity represents one of the major risk factor for early
      development of OA. In the obese population, knee replacement should be delayed
      and eventually avoided and prefer conservative treatments including intrarticular
      hyaluronic acid (HA) viscosupplementation. In the present clinical randomized
      trial, we present a comparison between two groups of 24 obese patients which were
      randomized to be treated with two intrarticular injections of hybrid (low and
      high molecular weight) hyaluronic acid (Group A) or two injections of high
      molecular weight hyaluronic acid (Group B). Patients were followed-up through to
      6 months and assessed though IKDC and KOOS scores, pain was evaluated with VAS.
      All patients reported a significant improvement when compared to baseline value
      in all outcome measures. At 3-month follow-up, IKDC had significantly improved in
      patients of Group A, compared to Group B (53.1+/-1.9 vs 51.4+/-2.4, p=0.0079) and
      the same for KOOS (52.1+/-2.0 vs 50.1+/-2.9, p=0.010). Furthermore, the
      difference in KOOS was persistently significant at 6-month follow-up (54.7+/-2.3
      vs 51.7+/-4.9, p=0.014). The VAS reduced significantly more in Group A at 3
      months (3.7+/-0.5 vs 5.2+/-0.7, p less than 0.001). In an obese population, where
      basal inflammatory pattern increases symptoms of OA and conservative treatment is
      recommended, HA viscosupplementation improved function and pain of the knee. The
      treatment with hybrid HA showed better outcomes than high molecular weight HA in
      obese patients. The combination of the anti-inflammatory action of low molecular
      weight HA on chondrocytes and the biomechanical role of high molecular weight HA
      might explain the different results.

PMID- 29202569
TI  - The use of hyaluronic acid as an adjuvant in the management of gingivitis.
AB  - Recently, a specifically designed device was proposed that is able to nebulize
      particles with a diameter of approximately 16 micrometres to be used mainly in
      the management of diseases of the upper airway respiratory tract. The purpose of
      this pilot study is to evaluate the potential efficacy of nebulized hyaluronic
      acid in the management of gingivitis. The results of the statistical analysis
      demonstrate that there was no difference between the pocket depth as measured in
      the treated sites at time 0 (pre-treatment) and time 1 (15 days post-treatment).
      However, the difference between bleeding on probing as measured at time 0 and
      time 1 indicated an improvement on both sides, with a slightly greater
      improvement on the side treated with HA.

PMID- 29202570
TI  - The use of hyaluronic acid as an adjuvant in the management of mucositis.
AB  - In recent years, with an increase in the number of implants, there has been a
      related increase in cases of pathologies related to infections around the implant
      site and on the implant surface i.e. mucositis and peri-implantitis. The purpose
      of this pilot study is to evaluate the potential efficacy of nebulized hyaluronic
      acid in the management of mucositis. The results of the statistical analysis
      demonstrate that there was no difference between the pocket depth as measured in
      the treated sites at time 0 (pre-treatment) and time 1 (15 days weeks post
      treatment). However, the difference between bleeding on probing as measured at
      time 0 and time 1 indicated an improvement on both sides, with a slightly greater
      improvement on the side treated with HA.

PMID- 29202571
TI  - The use of hyaluronic acid as an adjuvant in the management of periodontitis.
AB  - The emollient and restructuring action exerted on the mucous membranes by
      hyaluronic acid is of particular significance. This is thanks to its reparative
      (it stimulates angiogenesis) and soothing properties (hyaluronic acid is used in
      wound care to improve the processes of wound healing), which are effective in
      treating the symptoms of local inflammation and irritation. The purpose of this
      clinical trial is to evaluate the potential efficacy of nebulized hyaluronic acid
      in the management of chronic periodontitis in adults. The results of the
      statistical analysis demonstrate that there was a slight improvement in the
      measurement of pocket depth in the side treated with HA at time 0 (pre-treatment)
      and time 1 (15 days post-treatment). Furthermore, the difference between bleeding
      on probing as measured at time 0 and time 1 indicated an improvement on both
      sides, with a slightly greater improvement on the side treated with HA.

PMID- 29202572
TI  - The use of hyaluronic acid as an adjuvant in the management of peri-implantitis.
AB  - It is well known in dentistry that there are numerous chronic conditions that
      require ongoing and constant management over time, the most noteworthy being
      periodontal disease, gingivitis and periodontitis. Yet, in recent years, with the
      increase in the number of implants being placed, mucositis and peri-implantitis
      have become more and more prevalent pathologies. The results of the statistical
      analysis demonstrate that there was a slight difference between the pocket depth
      as measured in the treated sites at time 0 (pre-treatment) and time 1 (15 days
      post-treatment), although the difference was so small as to render it
      statistically irrelevant. Bleeding on probing as measured at time 0 and time 1
      indicated an improvement on both sides, but with no greater improvement noted on
      the side treated with HA.

PMID- 29202573
TI  - The use of hyaluronic acid as a support of two different micronized biomaterials
      in crestal sinus lift procedures. A report on two case studies with volume
      comparison.
AB  - In the context of the trans crestal maxillary sinus lift, a wide variety of
      biomaterials have been used to fill the sub-antral space over the years. The
      materials that have a pasty consistency and are smooth and free from lumps are
      the most suitable to come into contact with the Schneiderian membrane which, if
      torn, cannot perform its graft containment function. In this study, a micronized
      heterologous bone in a collagen matrix of two different percentages was used in
      order to fill the maxillary sinus. Before using biomaterial as filler, a spray
      form of hyaluronic acid was used to disinfect the surgical site before and after
      the surgery, along with more consistent and pasty form of gel of hyaluronic acid
      being used in order to facilitate the detachment of the membrane. The surgical
      procedures were designed and carried out using computer-planned surgery. The
      filling volume obtained was measured with a comparative software programme and
      using an ellissoid formula. This technique allows the surgery to be performed in
      a way that is both minimally traumatic and invasive, fully careful of the
      membrane and represents a viable alternative to those surgical techniques for
      crestal sinus lift currently in use.

PMID- 29202574
TI  - Effect of biostimulation on oral fibroblast: a pilot study.
AB  - Bio-stimulation is a technique in aesthetic medicine in which different drugs
      such as nucleotides, antioxidants and glucosaminoglycans precursors are injected
      in the dermis to improving the anabolic function of dermal fibroblasts, i.e.,
      protein synthesis, replication and production of extracellular matrix components.
      It can be achieved with multiple intra-dermal injections, using two protocols: 1)
      Polydeoxyribonucleotide (PDRN) plus glucosamine sulphate (Gluc); 2) N
      acetylcysteine (NAC) and amino acids (Aa) (named Bio- NAC procedure). Since the
      role of drugs used in biostimulation on human dermal fibroblasts is not
      completely understood, the aim of this study is to evaluate the effect of these
      substances in primary cell cultures by using RT-PCR and a panel of specific genes
      (ELN, DSP, FN1, FBN1, ITGA1, ITGA2, ITGA5, ITGB1, COL1A1,COL3A1) to detect their
      effect on cell metabolism and extracellular matrix components. Both the
      treatments were responsible for Elastine and Desmoplakin genes activation. Only
      NAC plus Aa treatment enhance the expression of other genes related to tissue
      growth and elasticity like FBN1, ITGA1 and ITGB1. All the other genes
      investigated (FN1, ITGA5, ITGA2, COL1A1, COL3A1) were down-regulated by both
      treatments. Since the precise role of these proteins in tissue integrity and
      aging is not known, this study confirms the usefulness of biostimulation
      therapies in enhancing some of the genes responsible of cellular wellbeing. This
      study could be useful to consider the possibility of injective biostimulation in
      oral cavity, clinical applications in oral healing and in gingival atrophy as
      well.

PMID- 29202575
TI  - Biorevitalization: an in vitro study on gingival fibroblast.
AB  - Bio-revitalization is a therapy commonly used in aesthetic medicine to improve
      skin quality by di!rectly integrating hyaluronic acid alone or added to other
      molecules (i.e. vitamins) through intradermal injections. These injections are
      not aimed to fill roughness but to achieve extracellular matrix optimi!zation.
      The injective medical devices used in aesthetic medicine differ for hyaluronic
      acid content and for the presence of additional molecules that characterize the
      formulation of a particular company. The aim of the present study is to compare
      HA with different compounds in regard to their effects on cultured fibroblasts
      over time by using RT-PCR and a panel of genes (ELN, DSP, FN1, FBN1, ITGA1,
      ITGA2, ITGA5, ITGB1, COL1A1, COL3A1) involved in connective integrity. Bio
      revitalization is able to activate genes involved in tissue integrity. The
      reported data add new insight in the comprehension of molecular mechanism related
      to BR. These preliminary data have to be developed through additional
      experiments. However, an injective therapy seems to be effective in gingival
      fibroblast stimulation.

PMID- 29202576
TI  - Poisson Model To Generate Isotope Distribution for Biomolecules.
AB  - We introduce a simplified computational algorithm for computing isotope
      distributions (relative abundances and masses) of biomolecules. The algorithm is
      based on Poisson approximation to binomial and multinomial distributions. It
      leads to a small number of arithmetic operations to compute isotope distributions
      of molecules. The approach uses three embedded loops to compute the isotope
      distributions, as compared with the eight embedded loops in exact calculations.
      The speed improvement is about 3-fold compared to the fast Fourier transformation
      based isotope calculations, often termed as ultrafast isotope calculation. The
      approach naturally incorporates the determination of the masses of each molecular
      isotopomer. It is applicable to high mass accuracy and resolution mass
      spectrometry data. The application to tryptic peptides in a UniProt protein
      database revealed that the mass accuracy of the computed isotopomers is better
      than 1 ppm. Even better mass accuracy (below 1 ppm) is achievable when the method
      is paired with the exact calculations, which we term a hybrid approach. The
      algorithms have been implemented in a freely available C/C++ code.

PMID- 29202577
TI  - All-Graphene-Based Highly Flexible Noncontact Electronic Skin.
AB  - Noncontact electronic skin (e-skin), which possesses superior long-range and high
      spatial-resolution sensory properties, is becoming indispensable in fulfilling
      the emulation of human sensation via prosthetics. Here, we present an advanced
      design and fabrication of all-graphene-based highly flexible noncontact e-skins
      by virtue of femtosecond laser direct writing (FsLDW). The photoreduced graphene
      oxide patterns function as the conductive electrodes, whereas the pristine
      graphene oxide thin film serves as the sensing layer. The as-fabricated e-skins
      exhibit high sensitivity, fast response-recovery behavior, good long-term
      stability, and excellent mechanical robustness. In-depth analysis reveals that
      the sensing mechanism is attributed to proton and ionic conductivity in the low
      and high humidity conditions, respectively. By taking the merits of the FsLDW, a
      4 * 4 sensing matrix is facilely integrated in a single-step, eco-friendly, and
      green process. The light-weight and in-plane matrix shows high-spatial-resolution
      sensing capabilities over a long detection range in a noncontact mode. This study
      will open up an avenue to innovations in the noncontact e-skins and hold a
      promise for applications in wearable human-machine interfaces, robotics, and
      bioelectronics.

PMID- 29202578
TI  - Label-Free Detection of Microvesicles and Proteins by the Bundling of Gliding
      Microtubules.
AB  - Development of miniaturized devices for the rapid and sensitive detection of
      analyte is crucial for various applications across healthcare, pharmaceutical,
      environmental, and other industries. Here, we report on the detection of
      unlabeled analyte by using fluorescently labeled, antibody-conjugated
      microtubules in a kinesin-1 gliding motility assay. The detection principle is
      based on the formation of fluorescent supramolecular assemblies of microtubule
      bundles and spools in the presence of multivalent analytes. We demonstrate the
      rapid, label-free detection of CD45+ microvesicles derived from leukemia cells.
      Moreover, we employ our platform for the label-free detection of multivalent
      proteins at subnanomolar concentrations, as well as for profiling the cross
      reactivity between commercially available secondary antibodies. As the detection
      principle is based on the molecular recognition between antigen and antibody, our
      method can find general application where it identifies any analyte, including
      clinically relevant microvesicles and proteins.

PMID- 29202579
TI  - Design and Analysis of Compact DNA Strand Displacement Circuits for Analog
      Computation Using Autocatalytic Amplifiers.
AB  - A main goal in DNA computing is to build DNA circuits to compute designated
      functions using a minimal number of DNA strands. Here, we propose a novel
      architecture to build compact DNA strand displacement circuits to compute a broad
      scope of functions in an analog fashion. A circuit by this architecture is
      composed of three autocatalytic amplifiers, and the amplifiers interact to
      perform computation. We show DNA circuits to compute functions sqrt(x), ln(x) and
      exp(x) for x in tunable ranges with simulation results. A key innovation in our
      architecture, inspired by Napier's use of logarithm transforms to compute square
      roots on a slide rule, is to make use of autocatalytic amplifiers to do
      logarithmic and exponential transforms in concentration and time. In particular,
      we convert from the input that is encoded by the initial concentration of the
      input DNA strand, to time, and then back again to the output encoded by the
      concentration of the output DNA strand at equilibrium. This combined use of
      strand-concentration and time encoding of computational values may have impact on
      other forms of molecular computation.

PMID- 29202580
TI  - Morphological Effects of CuO Nanostructures on Fibrillation of Human Serum
      Albumin.
AB  - The influence of different morphologies of nanostructures on amyloid fibrillation
      has been investigated by monitoring the fibrillation of human serum albumin (HSA)
      in the presence of rod-, sphere-, flower-, and star-shaped copper oxide (CuO)
      nanostructures. The different morphologies of CuO have been synthesized from an
      aqueous solution-based precipitation method using various organic acids, viz.,
      acetic acid, citric acid, and tartaric acid. The fibrillation process of HSA has
      been examined using various biophysical techniques, e.g., Thioflavin T
      fluorescence, Congo red binding studies through UV spectroscopy, circular
      dichroism spectroscopy, and fluorescence microscopy. The monolayer protein
      coverage on the CuO nanostructures has been established through DLS studies, and
      the well-fitted Langmuir isotherm model has been used to interpret the
      differential adsorption behavior of HSA molecules on the CuO nanostructures. The
      nanostar-shaped CuO, by virtue of their higher specific surface area (94.45 m2 g
      1), presence of high indexed facets {211} and high positive surface charge
      potential (+16.2 mV at pH 7.0) was found to show the highest adsorption of the
      HSA monomers and thus was more competent to inhibit the formation of HSA fibrils
      compared to the other nanostructures of CuO.

PMID- 29202582
TI  - Globular, Sponge-like to Layer-like Morphological Transition in 1-n-Alkyl-3
      methylimidazolium Octylsulfate Ionic Liquid Homologous Series.
AB  - Segregation of polar and nonpolar domains in ionic liquids for which either the
      cation or anion is responsible for inducing nonpolar domains is well understood.
      On the other hand, information regarding the nanoscale heterogeneities
      originating due to the presence of nonpolar content on both the ions is
      rudimentary at this point. The present contribution is aimed at addressing this
      question and focuses on a molecular dynamics simulation study to probe nanoscale
      structural and aggregation features of the 1-n-alkyl-3-methylimidazolium [Cnmim]
      octylsulfate [C8SO4] ionic liquid homologous series (n = 2, 4, 6, 8, 10, and 12).
      The objective of this work is to determine the effect of increasing alkyl chain
      length in the cation on nonpolar domain formation, especially when the alkyl
      chain lengths from both the ions participate in defining such domains. The
      results indicate that all the ionic liquids form nonpolar domains, morphology of
      which gradually changes from globular, sponge-like to layer-like structure with
      increase in the cationic alkyl chain length. The length of the nonpolar domains
      calculated from the total structure factor for [C10mim][C8SO4] is considerably
      higher than that reported for other imidazolium-based ionic liquid containing
      smaller anions. The structure factor for [C12mim][C8SO4] ionic liquid contains
      multiple intermediate peaks separating the charge alternation peak and pre-peak,
      which points to nonpolar domains of varying lengths, an observation that remains
      to be validated. Analysis of the heterogeneous order parameters and orientational
      correlation functions of the alkyl chains further suggests an increase in the
      spatial heterogeneity and long-range order along the homologous series. The
      origin of rich diversity of structures obtained by introducing nonpolar content
      on both the ions is discussed.

PMID- 29202581
TI  - Development of a Pigment-Based Whole-Cell Zinc Biosensor for Human Serum.
AB  - Deficiencies in vitamins and minerals (micronutrients) are a critical global
      health concern, in part due to logistical difficulties in assessing population
      micronutrient status. Whole-cell biosensors offer a unique opportunity to address
      this issue, with the potential to move sample analysis from centralized, resource
      intensive clinics to minimal-resource, on-site measurement. Here, we present a
      proof-of-concept whole-cell biosensor in Escherichia coli for detecting zinc, a
      micronutrient for which deficiencies are a significant public health burden.
      Importantly, the whole-cell biosensor produces readouts (pigments) that are
      visible to the naked eye, mitigating the need for measurement equipment and thus
      increasing feasibility for sensor field-friendliness and affordability at a
      global scale. Two zinc-responsive promoter/transcription factor systems are used
      to differentially control production of three distinctly colored pigments in
      response to zinc levels in culture. We demonstrate strategies for tuning each
      zinc-responsive system to turn production of the different pigments on and off at
      different zinc levels, and we demonstrate production of three distinct color
      regimes over a concentration range relevant to human health. We also demonstrate
      the ability of the sensor cells to grow and produce pigment when cultured in
      human serum, the ultimate target matrix for assessing zinc nutritional status.
      Specifically, we present approaches to overcome innate immune responses that
      would otherwise hinder bacterial sensor survival, and we demonstrate production
      of multiple pigment regimes in human serum with different zinc levels. This work
      provides proof of principle for the development of low-cost, minimal-equipment,
      field-deployable biosensors for nutritional epidemiology applications.

PMID- 29202583
TI  - 2018: The 90th Volume of Analytical Chemistry and Still Growing.

PMID- 29202584
TI  - Treatment of acute portomesenteric venous thrombosis with thrombectomy through a
      transjugular intrahepatic portosystemic shunt: a single-center experience.
AB  - Background Acute portomesenteric venous thrombosis (PMVT) is a potentially life
      threatening condition and urgent treatment is required. Purpose To
      retrospectively evaluate the efficacy and safety of treating acute PMVT by the
      creation of a transjugular intrahepatic portosystemic shunt (TIPS) followed by
      thrombectomy. Material and Methods Six patients (all men, age range = 39-51
      years) presenting with acute PMVT were treated with transjugular thrombectomy
      (TT) through a TIPS created in the same session. The intervention included
      iterated venography through the TIPS one to three times within the first week
      after diagnosis and repeated thrombectomy if needed (n = 5). Results
      Recanalization was successful with persistent blood flow through the main
      superior mesenteric vein, portal vein, and TIPS in all six patients. Five
      patients were treated primarily with thrombectomy through a TIPS with clinical
      improvement. The final patient was initially treated with surgical thrombectomy
      and bowel resection. TIPS and TT was performed two days after surgery due to re
      thrombosis but the patient deteriorated and died of multi-organ failure.
      Procedure-related complications were transient hematuria (n = 3) and transient
      encephalopathy (n = 2). In-hospital time was <14 days in four of the five
      patients with primary TIPS and TT. No sign of re-thrombosis was noted during
      follow-up (mean = 18 months, range = 8-28 months). Conclusion Thrombectomy
      through a TIPS is feasible and can be effective in recanalization and symptom
      relief in acute PMVT.

PMID- 29202585
TI  - Wellness Programs With Financial Incentives Through Disparities Lens.
AB  - PURPOSE: To examine wellness programs with financial incentives and their effect
      on disparities in preventive care. DESIGN: Financial incentives were introduced
      by 15 large employers, from 2010 to 2013. SETTING: Fifteen private employers.
      SUBJECTS: A total of 299 436 employees and adult dependents. MEASURES: Preventive
      services and participation in financial incentives. ANALYSIS: Multivariate linear
      regression. RESULTS: Disparities in preventive services widened after
      introduction of financial incentives. Asians were 3% more likely and African
      Americans were 3% less likely to receive wellness rewards than whites and non
      Hispanics, controlling for other factors. CONCLUSION: Federal law limits
      targeting of wellness financial incentives by subgroups; thus, employers should
      consider outreach and culturally appropriate messaging.

PMID- 29202586
TI  - Pharmacological treatments available for the management of underactive bladder in
      neurological conditions.
AB  - INTRODUCTION: Underactive bladder (UAB) is a common cause of lower urinary tract
      dysfunction which has an increasing incidence with aging. It is characterized as
      an incompetent detrusor contraction with reduced strength and/or duration to
      completely empty the bladder. UAB is observed in both men and women. The exact
      definition, classification, and pathophysiological mechanism responsible for UAB
      is still debatable, however neurologic, myogenic, and iatrogenic causes are
      explained. The symptom complex related to UAB includes hesitancy, diminished
      sensation of bladder filling, a slow urinary stream, increased post-void residue,
      and etc. Areas covered: We reviewed the current understanding of UAB with special
      focus on pharmacological treatments and potential pharmacotherapy options
      particularly in neurological conditions. Also, the definition, etiology,
      symptoms, diagnosis and management of UAB were discussed in this review. Expert
      commentary: The underlying mechanism of UAB is not clear yet. Therefore; the lack
      of efficient pharmacotherapies is evident in such patients. Prior to any decision
      for pharmacological or surgical interventions, the underlying causes of UAB and
      detrusor impairment in each patient should be distinguished. Future researches
      need to address the exact dynamics of detrusor contraction and the muscular and
      neurological contributors to UAB.

PMID- 29202587
TI  - Focussing on the foot in psoriatic arthritis: pathology and management options.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory
      arthritis characterised by a range of musculoskeletal conditions including
      enthesitis, dactylitis and synovitis as well as skin and nail manifestations. The
      foot is a complex mixture of tissues, all of which can be involved in this
      disease and is frequently the presenting feature. Areas covered: In this under
      researched area, articles were reviewed from the authors' publications as well as
      from other known authors. This review will discuss how PsA affects the foot and
      ankle with a particular focus on synovitis, tenosynovitis, enthesitis,
      dactylitis, bone erosion and psoriatic skin and nail disease. The use of imaging
      is discussed. Conventional radiography is consistently used, however magnetic
      resonance imaging and ultrasound should be used routinely to diagnose, assess and
      monitor the disease appropriately. The complex nature of PsA in the foot and
      ankle should be considered when managing the condition and treatment should be
      individualized to relieve pain, maintain mobility and improve quality of life.
      Expert commentary: The foot and ankle remains a neglected area in PsA. Problems
      with the foot and ankle should be prioritised as they can significantly impact on
      patients' quality of life. Focussing treatment on the foot and ankle can
      significantly improve outcome.

PMID- 29202588
TI  - Therapeutic drug monitoring of anti-TNF therapy in children with inflammatory
      bowel disease.
AB  - INTRODUCTION: Although anti-TNF therapy has changed the scenery of pediatric
      inflammatory bowel diseases (IBD) immensely, there are still patients with an
      unfortunate outcome. Approximately one third of patients that initially respond
      to anti-TNF therapy will lose that response over time and need treatment
      optimization. Loss of response (LOR) is a big concern in IBD management and
      especially among pediatric patients where treatment options are more limited than
      in adults. In children it is even more important to sustain response with minimal
      toxicity. Therapeutic drug monitoring (TDM) is proposed as a tool to reach this
      goal. Areas covered: This review focuses on the importance of TDM of anti-TNF and
      the role TDM has in clinical practice of pediatric IBD. Expert opinion: Although
      TDM is not yet widely used in pediatric IBD, the available literature suggests it
      to be a promising tool, especially in patients with LOR to anti-TNF. There is
      increasing evidence that also in children, higher anti-TNF drug levels are
      associated with sustained response, and likewise low or undetectable trough
      levels increase the likelihood of LOR. TDM-based treat to target strategies are
      being designed in adult studies, but more prospective studies also in pediatric
      IBD populations looking at the role of proactive testing are needed.

PMID- 29202589
TI  - Interstitial lung disease in systemic autoimmune rheumatic diseases: a
      comprehensive review.
AB  - BACKGROUND: Interstitial lung diseases (ILDs) are among the most serious
      complications associated with systemic rheumatic diseases, and lead to
      significant morbidity and mortality; they may also be the first manifestation of
      connective tissue diseases (CTDs). The aim of this narrative review is to
      summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing
      features in different rheumatic diseseas. Areas covered: The pathogenesis,
      clinical aspects and treatment of ILD associated with rheumatic systemic diseases
      and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library
      databases for papers published between 1995 and February 2017 using combinations
      of words or terms. Articles not written in English were excluded. Expert
      commentary: The management of CTD-ILD is challenging because of the lack of
      robust data regarding the treatments used, the heterogeneity of the diseases
      themselves, and the scarcity of well-defined outcome measures. Treatment
      decisions are often made clinically on the basis of functional, radiographic
      progression, and exacerbating factors such as age and the burden of
      comorbidities. Given the complexities of diagnosis and the paucity of treatment
      trials, the management of CTD patients with ILD requires multidisciplinary
      collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

PMID- 29202590
TI  - Delayed diagnosis in X-linked agammaglobulinemia and its relationship to the
      occurrence of mutations in BTK non-kinase domains.
AB  - BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by the absence of
      immunoglobulin and B cells. Patients suffer from recurrent bacterial infections
      from early childhood, and require lifelong immunoglobulin replacement therapy.
      Mutations in BTK (Bruton's Tyrosine Kinase) are associated with this phenotype.
      Some patients that present XLA do not show typical clinical symptoms, resulting
      in delayed diagnosis due to the lack of a severe phenotype. This study presents a
      report of five XLA patients from four different families and attempts to
      determine a relationship between delayed diagnosis and the occurrence of BTK
      mutations. METHODS: Samples from patients with antibody deficiency were analyzed
      to determine BTK expression, immunophenotyping and mutation analysis. Clinical
      and laboratory data was analyzed and presented for each patient. RESULTS: Most
      patients presented here showed atypical clinical and laboratory data for XLA,
      including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK
      protein. Sequencing of BTK showed that these patients harbored missense mutations
      in the pleckstrin homology and Src-homology-2 domains. When it was compared to
      public databases, BTK sequencing exhibited a new change, along with three other
      previously reported changes. CONCLUSIONS: Delayed diagnosis and atypical
      manifestations in XLA might be related to mutation type and BTK expression.

PMID- 29202592
TI  - Infected pulmonary aneurysm following pulmonary artery banding.
AB  - A 1-month-old girl, diagnosed with a common atrioventricular canal, moderate
      atrioventricular valvular regurgitation, and pulmonary hypertension, underwent
      pulmonary artery banding. Postoperatively, methicillin-resistant Staphylococcus
      aureus wound infection was treated with antibiotics. One month later, emergency
      surgery was performed for oozing rupture of an infected pulmonary aneurysm. The
      pulmonary aneurysm was completely resected, the banding tape was removed, and
      pulmonary angioplasty was performed to create pulmonary stenosis without using
      foreign material. Methicillin-resistant Staphylococcus aureus was cultured from
      the resected tissues and banding tape. The patient was discharged after
      antibiotic administration. Correction was performed at 1 year of age, and she
      remains well.

PMID- 29202591
TI  - Venom immunotherapy in patients with allergic reactions to insect stings.
AB  - INTRODUCTION: Allergy to Hymenoptera (Apis mellifera, Vespula species, Polistes
      species, Vespa crabro) venom can be safely and effectively treated by venom
      immunotherapy (VIT), which in the 40 years since its introduction has been able
      to prevent reactions to stings, and to treatment as well, though systemic
      reactions, occasionally severe, are possible. Areas covered: We reviewed the
      recent literature on VIT by searching in PubMed for the terms 'venom
      immunotherapy' and 'Hymenoptera venom immunotherapy' to highlight the current
      status of VIT and the likely development in the coming years. Expert commentary:
      VIT, provided the correct choice of the venom and adequate venom preparations and
      maintenance doses are used, is a treatment of great value in preventing systemic
      reactions to Hymenoptera stings. A 5-year duration ensures a prolonged tolerance
      to stings following VIT discontinuation, unless patients suffer from
      mastocytosis. In fact, due to reports of fatal reactions after stopping VIT,
      patients with mastocytosis, or with very severe reactions to stings, need an
      indefinite duration of treatment.

PMID- 29202593
TI  - Ipragliflozin and sodium glucose transporter 2 inhibitors to reduce liver fat:
      will the prize we sought be won?

PMID- 29202594
TI  - Diagnosing and managing patients with drug hypersensitivity.
AB  - INTRODUCTION: Diagnosing and managing drug hypersensitivity is challenging
      because there are no clear limits between different types of drug reactions.
      Distinguishing between type A (predictable) and type B (hypersensitivity)
      reactions when a drug is introduced on the market is not easy. When many people
      use a drug, adverse reactions can occur, conditioned by diverse genetic profiles,
      viral infections or concomitant therapy. Occasionally the only tool clinicians
      have on which to base the diagnosis is the clinical history. Skins tests or in
      vitro tests sometimes have low sensitivity or are unavailable, and drug
      provocation tests may be dangerous or strictly forbidden in case of severe
      cutaneous reactions. Areas covered: This paper reviews the diagnosis and
      management of the two main types of immunological reactions: IgE-mediated
      immediate drug hypersensitivity reactions (IDHRs) and non-immediate drug
      hypersensitivity reactions (NIDHRs). Expert commentary: Although Europe and the
      United States use different diagnostic methods, patients with history of drug
      hypersensitivity must avoid the suspicious drug, and clinicians must assess
      tolerance to safe alternatives under medical surveillance. Sometimes
      desensitization may be required. There is a consensus about the need to perform
      genetic testing for specific drugs and give patients proper documentation to
      prevent future exposure to culprit drugs.

PMID- 29202595
TI  - Biological therapies targeting arrhythmias: are cells and genes the answer?
AB  - INTRODUCTION: Arrhythmias can cause symptoms ranging from simple dizziness to
      life-threatening circulatory collapse. Current management includes medical
      therapy and procedures such as catheter ablation or device implantation. However,
      these strategies still pose a risk of serious side effects, and some patients
      remain symptomatic. Advancement in our understanding of how arrhythmias develop
      on the cellular level has made more targeted approaches possible. In addition,
      contemporary studies have found that several genes are involved in the
      pathogenesis of arrhythmias. Areas covered: In the present review, the authors
      explore the cellular and genetic mechanisms leading to arrhythmias as well as the
      progress that has been made in using both gene and cell therapy to treat tachy-
      and bradyarrhythmias. They also consider why gene and cell therapy has resulted
      into a few clinical trials with promising results, however still not applicable
      in routine clinical practice. Expert opinion: The question currently is whether
      such biological therapies could replace current established approaches. The
      contemporary evidence suggests that despite recent advances in this field, it
      will need more work in experimental models before this is applied into clinical
      practice. Gene and cell studies targeting conduction and repolarization are
      promising, but still not ready for use in the clinical setting.

PMID- 29202596
TI  - 12-Epi-9-deacetoxyxenicin, new cytotoxic diterpenoid from a Bornean soft coral,
      Xenia sp.
AB  - One new compound, 12-epi-9-deacetoxyxenicin (1) along with a hydroperoxide
      product, 12-epi-9-deacetoxy-8-hydroperoxyxenicin (2) and two known
      sesquiterpenoids (3-4) were isolated from a population of Bornean soft coral
      Xenia sp. The structures of these secondary metabolites were elucidated based on
      their spectroscopic data. Compounds 1 and 2 showed cytotoxic activity against ATL
      cell line, S1T. In addition, compound 3 exhibited hyphal inhibition of Lagenidium
      thermophilum.

PMID- 29202597
TI  - A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots
      of Juglans mandshurica and their anti-inflammatory activities.
AB  - A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3
      methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3
      dihydroxy-5-O-beta-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4
      hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3),
      rhoiptelol B (4) and 3',4"-epoxy-2-O-beta-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7
      (3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans
      mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified
      based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1-5 were
      assayed for their inhibitory effects on the production of NO, TNF-alpha and IL-6
      in LPS-stimulated RAW264.7 cells.

PMID- 29202598
TI  - Speech-language pathologists as determiners of the human right to diversity in
      communication for school children in the US.
AB  - Article 19 of the Universal Declaration of Human Rights states that everyone has
      the right to freedom of opinion and expression - the right to communication.
      Communication is at the core of the speech-language pathology (SLP) profession.
      Yet, while we celebrate the 70th anniversary of the Universal Declaration of
      Human Rights some of our most vulnerable youth are being placed in special
      education at disproportional rates. School-based SLPs in the United States may be
      unwittingly contributing to this phenomenon, obstructing the human right to
      communication because of biased assessment procedures. However, increasing
      cultural competence, diversifying the profession, and utilising additional
      assessment measures are actions that can be taken to promote equity in assessment
      for all children.

PMID- 29202599
TI  - Bereaved Parents' Health Status During the First 6 Months After Their Child's
      Death.
AB  - PURPOSE: To examine bereaved parents' physical, mental, and social health during
      the first 6 months after their child's (<12 years) death from a life-threatening
      illness. BACKGROUND AND SIGNIFICANCE: Bereaved parents have higher mortality and
      morbidity rates when compared to nonbereaved parents. Acute illnesses,
      hospitalizations, and medication changes are highest in the first 6 months. An
      understanding of bereaved parents' health risk indicators can help inform
      development of health promotion and disease prevention measures. Methods and
      Analysis: A prospective descriptive study examined 8 parent dyads. Parents
      completed health surveys (Patient-Reported Outcomes Measurement Information
      System-global, social, and sleep; Brief Symptom Inventory [BSI] 18), which are
      used to assess parents' health at 3 and 6 months after their child's death.
      Demographic data included a medical history, hospital or emergency department
      visits, and smoking and alcohol intake. Descriptive statistics were used to
      compare parents' scores to US general population scores. FINDINGS: Mothers' and
      fathers' physical, mental, and sleep health scores were typically within 1 to 2
      standard deviations of the population norms. However, their social health scores
      were as low as 3 standard deviations and all parents' scores were below
      population norms. Four (25%) of the 16 parents had new diagnosis during the first
      6 months. Based on the BSI-18, 3 parents had their scores above population
      cutoffs, which warranted a need for further clinical evaluation. CONCLUSIONS:
      Health data highlight the "at-risk" health status of bereaved parents. Further
      validation of these data is required to support the development of health
      promotion and disease prevention programs.

PMID- 29202600
TI  - Structural and functional insight of New Delhi Metallo beta-lactamase-1 variants.
AB  - New Delhi Metallo beta-lactamase-1 (NDM-1) is a member of the Metallo-beta
      lactamase family, capable of catalyzing the hydrolysis of all beta-lactam
      antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a
      worldwide concern to health workers. Seventeen different variants of NDM have
      been reported so far, across the world. These variants varied in their sequences
      either by single or multiple amino acid substitutions. This review summarizes the
      crystal structure of NDM and provides a comparative analysis of all variants.
      Moreover, we have for the first time highlighted the role of alpha-helix, beta
      sheet and loop structures of NDM enzyme, having different mutations occurred in
      these regions. The effect of these substitutions on its structure and functional
      aspect has to be thoroughly understood to design effective inhibitors in future.

PMID- 29202601
TI  - Hematological Parameters Outperform Plasma Markers in Predicting Long-Term
      Mortality After Coronary Angiography.
AB  - High-sensitivity troponin I (hsTnI) and N-terminal pro-brain natriuretic peptide
      (NT-pro-BNP) are predictors of coronary artery disease. Recently, routine
      hematological parameters emerged as mortality predictors. We examined the
      predictive value of hematological parameters (from the Utrecht Patient Oriented
      Database) and hsTnI and NT-pro-BNP for mortality in a coronary angiography
      population (Utrecht Coronary Biobank n = 1913). Using Cox regression, receiver
      operating characteristics, integrated discrimination improvement (IDI), and
      continuous net reclassification improvement (cNRI) analysis, we compared the
      predictive properties of hematological parameters with hsTnI and NT-pro-BNP for
      mortality. During a median follow-up duration of 1.8 years, 77 deaths occurred. A
      panel of 7 hematological parameters (leukocyte count, reticulocyte mean
      corpuscular hemoglobin concentration, red blood cell [RBC] green (FL1)
      fluorescence, %neutrophils, %large [>120 fL] RBCs, %monocytes, and coefficient of
      variation of neutrophil complexity) was highly predictive. Added to clinical
      characteristics, hematological parameters (area under the curve [AUC]: 0.855, P <
      .001; IDI: 0.04, P = .02; cNRI: 0.41, P < .001) were better predictors than hsTnI
      (AUC: 0.818) or NT-pro-BNP (AUC: 0.834) alone or combined (AUC: 0.834).
      Hematological parameters may provide mortality risk information following
      coronary angiography and may be superior to hsTnI and/or NT-pro-BNP.

PMID- 29202602
TI  - Clinical significance of serum anti-GM-CSF autoantibody levels in autoimmune
      pulmonary alveolar proteinosis.
AB  - AIM: Precise clinical significance of antigranulocyte-macrophage colony
      stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar
      proteinosis (aPAP) has not been well studied. METHODS: We obtained sera from 50
      healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic
      interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP
      patients was assessed by scoring computed tomography images in 19 patients.
      RESULTS: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and
      other diffuse lung diseases was 2.8 MUg/ml with 100% sensitivity and 98%
      specificity. Antibody levels at baseline were significantly lower in the improved
      group than in the unimproved group (p = 0.008). CONCLUSION: Our results indicate
      the existence of threshold levels of serum anti-GM-CSF IgG for the development
      and persistence of aPAP.

PMID- 29202603
TI  - The Influence of Race on Plasma Thrombin Generation In Healthy Subjects In
      Singapore.
AB  - Race is touted as an independent risk factor for venous thromboembolism (VTE),
      although the basis for this is varied and contentious. Comparison of plasma
      thrombin generation (TG) using calibrated automated thrombogram (CAT) across
      races offers a modality that objectively measures global hemostatic function to
      evaluate this influence. Direct comparative data across races are currently not
      available. Aim is to establish the influence of race on plasma TG. Sixty normal
      participants, matched for age and gender, equally representing 4 races-Caucasian,
      Chinese, Indian, and Malay-were recruited. Thrombin generation parameters (lag
      time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet
      poor plasma were measured using CAT. The mean ETP (standard deviation) for the
      different races were Caucasians: 1338.18 (194.19) nM.min; Chinese, 1318.91
      (108.90) nM.min; Indians, 1389.81 (182.61) nM.min; and Malays, 1436.21 (184.24)
      nM.min. Caucasians had the longest mean lag time of 2.59 +/- 0.37 seconds;
      Indians had the highest mean peak of 284.22 +/- 30.74 nM, and Malays had the
      longest mean time to peak of 5.47 +/- 0.59 seconds. Analysis based on race did
      not demonstrate any significant difference for all TG parameters. The greatest
      mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM.min
      (95% confidence interval: -45.86 to 280.46 nM.min) which was within the
      predefined limit of equivalence. In a cohort of healthy participants, TG mediated
      by plasma factors is not influenced by race and does not explain the reported
      racial differences in VTE incidence. For the 4 racial groups studied, the use of
      separate normal ranges for plasma TG might not be essential.

PMID- 29202604
TI  - Characterization of Von Willebrand Factor Multimer Structure in Patients With
      Severe Aortic Stenosis.
AB  - Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis
      (AS) has been frequently subclassified into a subtype 2A based on the deficiency
      of high-molecular-weight (HMW) multimers as it is seen in inherited von
      Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type
      2A does not only include an HMW deficiency but also a decrease in intermediate
      molecular-weight (IMW) multimers and an abnormal inner triplet band pattern.
      These additional characteristics have not been evaluated in AVWS associated with
      severe AS. Therefore, we recruited N = 31 consecutive patients with severe AS and
      performed a high-resolution Western blot with densitometrical band quantification
      to characterize the von Willebrand factor (VWF) multimeric structure and
      reevaluate the AVWS subtype classification. Study patients showed an isolated HMW
      VWF multimer deficiency without additional abnormalities of the IMW portions and
      the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS
      associated with severe AS does neither resemble that seen in AVWS type 2A nor
      that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A
      should not be used.

PMID- 29202605
TI  - Toxic Epidermal Necrolysis Spectrum Management at Sunnybrook Health Sciences
      Centre: Our Multidisciplinary Approach After Review of the Current Evidence.
AB  - Toxic epidermal necrolysis spectrum (TENS) is a rare yet severe adverse drug
      reaction associated with a high mortality rate. Beyond supportive care, there is
      still no established therapy for TENS, although recent meta-analyses and UK
      guideline recommendations have attempted to offer a review of relevant literature
      on this difficult topic. As most directed treatments lack clear consensual
      evidence, care centres often resort to establishing their own strategies. As
      Canada's largest adult burn centre and the provincial reference centre for most
      burn patients in Ontario, our team at the Ross Tilley Burn Centre, in
      collaboration with the Department of Dermatology at Sunnybrook Health Sciences
      Centre, Toronto, Canada, has managed over 60 confirmed cases of TENS over the
      past 2 decades. We would like to share our management, experience, and present
      our treatment protocol that we recently established by a collaborative
      multidisciplinary team approach to help guide treatment of these complex patients
      not only in Canada but worldwide.

PMID- 29202606
TI  - Results From a Pilot Video Intervention to Increase Cervical Cancer Screening in
      Refugee Women.
AB  - Many refugee women emigrate from countries with high cervical cancer incidence
      rates and have low rates of cervical cancer screening both before and after
      resettlement. Refugee women face many barriers to cervical cancer screening,
      including limited knowledge of cervical cancer and screening recommendations and
      cultural and linguistic barriers to being screened. Our pilot study aimed to
      develop and evaluate educational videos to promote cervical cancer screening
      among Karen-Burmese and Nepali-Bhutanese refugees, two of the largest groups of
      refugees arriving to the United States in recent years. We developed culturally
      tailored narrative videos for each ethnic group. Karen-Burmese and Nepali
      Bhutanese women ( N = 40) were recruited through community health educators to
      participate in a pre- and posttest study. We assessed changes in cervical cancer
      knowledge and intentions to be screened, and satisfaction with the videos. We
      found that women were significantly more likely to report having heard of a test
      for cervical cancer and indicated significantly greater intentions to be screened
      after watching the video. Their knowledge about cervical cancer and screening
      also improved significantly, and they reported high levels of acceptability with
      the video. Our results suggest that culturally tailored narrative educational
      videos were acceptable to the target audiences and may be effective in increasing
      cervical cancer screening among refugee women. Further research should assess how
      health care and social service providers could implement video-based
      interventions to encourage women to be screened for cervical cancer during early
      resettlement.

PMID- 29202607
TI  - Anxiety-related symptomatology in young children on the autism spectrum.
AB  - Anxiety symptomatology is frequently reported in autistic children, and the
      prevalence of anxiety disorder is estimated at around 40%. However, most studies
      have focused upon children of age 8 years or above, so little is known about
      early signs of anxiety in younger children with autism. This study sought to
      describe anxiety-related symptomatology in 95 5- to 6-year-old autistic children
      using the Anxiety Scale for Children with Autism Spectrum Disorder. Wide
      variability was found in levels of symptomatology with the most frequently
      reported items within the 'uncertainty' subscale and the least frequently
      reported items in the 'anxious arousal' subscale. Comparisons of those with
      scores less than or greater than 70 on adaptive behaviour suggests some influence
      of ability on presentation of anxiety-related symptomatology.

PMID- 29202608
TI  - Impact of climate and air pollution on acute coronary syndromes: an update from
      the European Society of Cardiology Congress 2017.

PMID- 29202609
TI  - The ability of PAM50 risk of recurrence score to predict 10-year distant
      recurrence in hormone receptor-positive postmenopausal women with special
      histological subtypes.
AB  - INTRODUCTION: The Prosigna-PAM50 risk of recurrence (ROR) score has been
      validated in randomized clinical trials to predict 10-year distant recurrence
      (DR) in hormone receptor-positive breast cancer. Here, we examine the ability of
      Prosigna for predicting DR at 10 years in a subgroup of postmenopausal breast
      cancer patients with special histological subtypes. METHODS: Using the population
      based Danish Breast Cancer Group database, follow-up data were collected on all
      patients diagnosed from 2000 to 2003 with estrogen receptor (ER)-positive and
      human epidermal growth factor receptor 2 (HER2) normal breast cancer who by
      nationwide guidelines were treated with 5 year of endocrine therapy (N = 2558).
      Among patients with 1 to 3 positive lymph nodes or a tumor size >20 mm, we
      identified 1570 with invasive ductal carcinoma (IDC) and 89 with special
      histological subtypes (apocrine, medullary, mucinous, papillary, secretory,
      tubular, neuroendocrine) who were tested with Prosigna. Fine and Gray models were
      applied to determine the prognostic value of the Prosigna-PAM50 ROR score for DR
      special subtypes as compared to IDC. RESULTS: Median follow-up for DR was 9.2
      year and for OS 15.2 year. The 10-year DR rate for the special subtypes was 9.2%
      (95% CI: 4.0% to 17.2%) as compared to 13.7% (95% CI: 11.9% to 15.7%) for IDC.
      The 10-year OS was 74.2% (95% CI: 63.7% to 82.0%) for the special subtypes and
      75.4% (95% CI: 73.2% to 77.4%) for IDC. Prosigna showed a statistical significant
      association of the continuous ROR score with risk of DR for both IDC and the
      special subtypes (IDC: p < .0001; special subtypes: p = .01). CONCLUSION: In the
      present study, we demonstrated that Prosigna-PAM50 continuous ROR score added
      significant prognostic information for 10-year DR in postmenopausal patients with
      special subtypes (tumor size >20 mm or 1 to 3 positive lymph nodes) and ER
      positive, HER2-normal early breast cancer.

PMID- 29202610
TI  - Occult breast cancer in breast reduction specimens.

PMID- 29202611
TI  - Aurora kinase A as a possible marker for endocrine resistance in early estrogen
      receptor positive breast cancer.
AB  - BACKGROUND: Cell culture studies have disclosed that the mitotic Aurora kinase A
      is causally involved in both tamoxifen and aromatase inhibitor resistant cell
      growth and thus may be a potential new marker for endocrine resistance in the
      clinical setting. MATERIAL AND METHODS: Archival tumor tissue was available from
      1323 Danish patients with estrogen receptor (ER) positive primary breast cancer,
      who participated in the Breast International Group (BIG) 1-98 trial, comparing
      treatment with tamoxifen and letrozole and both in a sequence. The expression of
      Aurora A was determined by immunohistochemistry in 980 tumors and semi
      quantitively scored into three groups; negative/weak, moderate and high. The
      Aurora A expression levels were compared to other clinico-pathological parameters
      and outcome, defined as disease-free survival (DFS) and overall survival (OS).
      RESULTS: High expression of Aurora A was found in 26.9% of patients and moderate
      in 57.0%. High expression was significantly associated with high malignancy grade
      and HER2 amplification. High Aurora A expression was significantly more frequent
      in ductal compared to lobular carcinomas. We found no significant association
      between Aurora A expression and DFS or OS and no evidence of interaction between
      Aurora A expression and benefits from tamoxifen versus letrozole. CONCLUSIONS:
      Aurora A expression in breast tumors was associated with high malignancy grade
      III and with HER2 amplification. A trend as a prognostic factor for OS was found
      in patients with high Aurora A expression. No predictive property was observed in
      this study with early breast cancer.

PMID- 29202612
TI  - Cone beam computed tomography imaging of superior semicircular canal morphology:
      a retrospective comparison of cleft lip/palate patients and normal controls.
AB  - OBJECTIVE: This study evaluated the prevalence and morphological characteristics
      of the superior semicircular canal (SSCC) in cleft lip and palate (CL/P) patients
      using cone beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT images of
      53 CL/P patients (28 males and 25 females) and a control group of 76 patients (42
      males and 34 females) were evaluated. Retrospectively, 258 temporal bone images
      from 129 patients were evaluated in terms of SSCC morphology and divided into a
      normal pattern (0.6-1.7 mm in thickness), a papyraceous pattern (<0.5 mm), a
      thick pattern (>1.8 mm), a pneumatized pattern and dehiscent. The chi-squared
      test was used to compare differences among semicircular canal dehiscence (SSCD)
      patterns in the CL/P and control groups; p <= .05 was taken to reflect
      statistical significance. RESULTS: The characteristics of the SSCC were evaluated
      on CBCT images in patients with CL/P and controls. In total, 158 (61%) cases were
      normal (0.6-1.7 mm in thickness), 31 (12%) papyraceous (<0.5 mm), 8 (3%) thick,
      and 34 (13%) pneumatized. SSCD was observed in 27 (11%) cases. Statistically
      significant differences between the CL/P and control groups were evident in terms
      of SSCC morphology (p < .001). CONCLUSIONS: SSCD should be considered if a CL/P
      patient exhibits a vestibular system deficiency. Oral and maxillofacial
      radiologists should pay attention to SSCD when interpreting CBCT images. Future
      studies should use high-level spatial resolution CBCT to focus on cleft site and
      SSCC morphology in larger patient populations.

PMID- 29202613
TI  - The effects of infection on severe stroke patients in the neurological intensive
      care unit in China.
AB  - OBJECTIVE: To study the effects of infection on severe stroke patients in the
      neurological intensive care unit and to find the related risk factors for
      mortality of severe stroke patients. METHODS: We conducted a retrospective study
      including 343 patients with ischaemic or haemorrhagic stroke and staying for more
      than 2 patient-days in the neurological intensive care unit at Beijing Chaoyang
      Hospital from January 2011 to December 2015 to analyse the infection features of
      patients with severe stroke in the neurological intensive care unit. All analyses
      were conducted using SPSS 18.0. RESULTS: The mortality rate, hospital staying
      time and hospital costs between infected and uninfected stroke patients were
      higher in the infected patients than in the uninfected patients, P < 0.05, and
      except for the hospital staying time, the mortality rate and hospital costs were
      both significantly higher in the infected patients. Respiratory tract infection
      was the most common infection type at all time periods, P < 0.05. However,
      urinary tract infection increased at 72 h after stroke compared with infection
      within 72 h after stroke. Blood sugar level, mean arterial pressure, scores of
      APACHE II, history of stroke, history of heart diseases, infections and
      respiratory tract infection were significantly different in dead patients
      compared with the alive patients, P < 0.05. CONCLUSION: Infection can
      significantly influence the mortality rate and hospital costs of stroke patients,
      and is an independent risk factor for mortality of stroke patients.

PMID- 29202614
TI  - Liquid biopsies in gastrointestinal malignancies: when is the big day?
AB  - INTRODUCTION: Tumor tissue sample is currently the gold standard for diagnosing
      gastrointestinal cancers, but also for genomic/immune component analyses that can
      help in the selection of therapy. However, this approach of studying a
      'representative' sample of the tumor does not address inherent heterogeneity.
      Liquid biopsies, mainly represented by circulating tumor cells, circulating tumor
      DNA, tumor exosomes, and microRNAs, have the potential to assess various
      biomarkers for early detection of cancer, carrying out genomic/immune profiling
      for not only selection of appropriate therapy but also to monitor effect of
      therapy. Areas covered: This review summarizes the current evidence in the
      literature on liquid biopsies in gastrointestinal cancers concerning diagnosis,
      prognosis, and response to therapy. The following terms were used in PubMed:
      'esophageal', 'gastric', 'colorectal', 'cancer', 'circulating tumor cells',
      'circulating tumor DNA', microRNA', 'diagnosis', 'prognosis', 'response',
      'resistance'. Expert commentary: Data increasingly supports the potential of
      liquid biopsies for early detection, selection of therapy, and monitoring
      response to therapy. One major question is whether assaying various components of
      the blood would accommodate considerable context-dependent heterogeneity of
      gastrointestinal tumors. There are many potential strategies to exploit liquid
      biopsy use. To put them in to perspective, well-designed and meticulous
      prospective studies will be needed to prove their usefulness.

PMID- 29202615
TI  - The accuracy of preoperative staging of the axilla in primary breast cancer: a
      national register based study on behalf of Danish Breast Cancer Group (DBCG).

PMID- 29202616
TI  - Series: Practical guidance to qualitative research. Part 4: Trustworthiness and
      publishing.
AB  - In the course of our supervisory work over the years we have noticed that
      qualitative research tends to evoke a lot of questions and worries, so-called
      frequently asked questions (FAQs). This series of four articles intends to
      provide novice researchers with practical guidance for conducting high-quality
      qualitative research in primary care. By 'novice' we mean Master's students and
      junior researchers, as well as experienced quantitative researchers who are
      engaging in qualitative research for the first time. This series addresses their
      questions and provides researchers, readers, reviewers and editors with
      references to criteria and tools for judging the quality of qualitative research
      papers. The first article provides an introduction to this series. The second
      article focused on context, research questions and designs. The third article
      focused on sampling, data collection and analysis. This fourth article addresses
      FAQs about trustworthiness and publishing. Quality criteria for all qualitative
      research are credibility, transferability, dependability, and confirmability.
      Reflexivity is an integral part of ensuring the transparency and quality of
      qualitative research. Writing a qualitative research article reflects the
      iterative nature of the qualitative research process: data analysis continues
      while writing. A qualitative research article is mostly narrative and tends to be
      longer than a quantitative paper, and sometimes requires a different structure.
      Editors essentially use the criteria: is it new, is it true, is it relevant? An
      effective cover letter enhances confidence in the newness, trueness and
      relevance, and explains why your study required a qualitative design. It provides
      information about the way you applied quality criteria or a checklist, and you
      can attach the checklist to the manuscript.

PMID- 29202617
TI  - Prevalence of polycystic ovary syndrome in Thai University adolescents.
AB  - Polycystic ovarian syndrome (PCOS) is a common and complex condition
      characterized by endocrine features and influenced by genetic and environmental
      factors. In Southeast Asia and Thailand, the prevalence of PCOS is unknown. The
      aim of this study was to estimate the prevalence of and determine factors
      associated with PCOS in Thai adolescents. We administered a validated
      questionnaire to 600 university female participants aged 17-19 years from Mahidol
      University in Bangkok. Of these, 548 (91.33%) responded and agreed to
      participate. Two-hundred and seventy-nine girls (50.91%) were identified as
      likely having PCOS and defined as 'probable cases'. Of those 279 participants,
      248 (88.88%) were evaluated further for PCOS using the Rotterdam criteria. A
      complete history was taken, and a physical examination including trans-abdominal
      ultrasound was performed. Blood chemistry tests were performed to exclude similar
      conditions and to investigate potential co-morbidities. The prevalence of PCOS in
      Thai adolescents was found to be 5.29%. After multivariate analyses, moderate
      acne was the strongest risk factor for PCOS. The odd ratios (95% confidence
      interval) for the presence of mild acne, moderate acne, and oligo- or amenorrhea
      in participants with PCOS were 2.83 (1.01-7.90; p = .47), 31.69 (10.07-99.67; p <
      .001), and 5.89 (2.42-14.37; p < .001), respectively.

PMID- 29202619
TI  - Provision of data from the clinical database and of biological material from the
      tumor bank of the Danish Breast Cancer Cooperative Group 2008-2017.

PMID- 29202618
TI  - Synovial fluid proteomics in the pursuit of arthritis mediators: An evolving
      field of novel biomarker discovery.
AB  - Synovial fluid (SF) is a protein-rich fluid produced into the joint cavity by
      cells of the synovial membrane. Due to its direct contact with articular
      cartilage, surfaces of the bone, and the synoviocytes of the inner membrane, it
      provides a promising reflection of the biochemical state of the joint under
      varying physiological and pathophysiological conditions. This property of SF has
      been exploited within numerous studies in search of unique biomarkers of joint
      pathologies with the ultimate goal of developing minimally invasive clinical
      assays to detect and/or monitor disease states. Several proteomic methodologies
      have been employed to mine the SF proteome. From elementary immunoassays to high
      throughput analyses using mass spectrometry-based techniques, each has
      demonstrated distinct advantages and disadvantages in the identification and
      quantification of SF proteins. This review will explore the role of SF in the
      elucidation of the arthritis proteome and the extent to which high-throughput
      techniques have facilitated the discovery and validation of protein biomarkers
      from osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA),
      and juvenile idiopathic arthritis (JIA) patients.

PMID- 29202620
TI  - Influence of intra-tumoral heterogeneity on the evaluation of BCL2, E-cadherin,
      EGFR, EMMPRIN, and Ki-67 expression in tissue microarrays from breast cancer.
AB  - INTRODUCTION: The influence of intra-tumoral heterogeneity on the evaluation of
      immunohistochemical (IHC) biomarker expression may affect the analytical validity
      of new biomarkers substantially and hence compromise the clinical utility. The
      aim of this study was to examine the influence of intra-tumoral heterogeneity as
      well as inter-observer variability on the evaluation of various IHC markers with
      potential prognostic impact in breast cancer (BCL2, E-cadherin, EGFR, EMMPRIN and
      Ki-67). MATERIAL AND METHODS: From each of 27 breast cancer patients, two tumor
      containing paraffin blocks were chosen. Intra-tumoral heterogeneity was evaluated
      (1) within a single tumor-containing paraffin block ('intra-block agreement') by
      comparing information from a central, a peripheral tissue microarray (TMA) core
      and a whole slide section (WS), (2) between two different tumor-containing blocks
      from the same primary tumor ('inter-block agreement') by comparing information
      from TMA cores (central/peripheral) and WS. IHC markers on WS and TMA cores were
      evaluated by two observers independently, and agreements were estimated by Kappa
      statistics. RESULTS: For BCL2, E-cadherin and EGFR, an almost perfect intra- and
      inter-block agreement was found. EMMPRIN and Ki-67 showed a more heterogeneous
      expression with moderate to substantial intra-block agreements. For both
      stainings, there was a moderate inter-block agreement that improved slightly for
      EMMPRIN, when using WS instead of TMA cores. Inter-observer agreements were found
      to be almost perfect for BCL2, E-cadherin and EGFR (WS: kappa > 0.82, TMAs: kappa
      > 0.90), substantial for EMMPRIN (kappa > 0.63), but only fair to moderate for Ki
      67 (WS: kappa = 0.54, TMAs: kappa = 0.33). CONCLUSIONS: BCL2, E-cadherin and EGFR
      were found to be homogeneously expressed, whereas EMMPRIN and Ki-67 showed a more
      pronounced degree of intra-tumoral heterogeneity. The results emphasize the
      importance of securing the analytical validity of new biomarkers by examining the
      intra-tumoral heterogeneity of immunohistochemical stainings applied to TMA cores
      individually in each type of cancer.

PMID- 29202621
TI  - The clinical database and implementation of treatment guidelines by the Danish
      Breast Cancer Cooperative Group in 2007-2016.
AB  - BACKGROUND: Since 40 years, Danish Breast Cancer Cooperative Group (DBCG) has
      provided comprehensive guidelines for diagnosis and treatment of breast cancer.
      This population-based analysis aimed to describe the plurality of modifications
      introduced over the past 10 years in the national Danish guidelines for the
      management of early breast cancer. By use of the clinical DBCG database we
      analyze the effectiveness of the implementation of guideline revisions in
      Denmark. METHODS: From the DBCG guidelines we extracted modifications introduced
      in 2007-2016 and selected examples regarding surgery, radiotherapy (RT) and
      systemic treatment. We assessed introduction of modifications from release on the
      DBCG webpage to change in clinical practice using the DBCG clinical database.
      RESULTS: Over a 10-year period data from 48,772 patients newly diagnosed with
      malignant breast tumors were entered into DBCG's clinical database and 42,197 of
      these patients were diagnosed with an invasive carcinoma following breast
      conserving surgery (BCS) or mastectomy. More than twenty modifications were
      introduced in the guidelines. Implementations, based on prospectively collected
      data, varied widely; exemplified with around one quarter of the patients not
      treated according to a specific guideline within one year from the introduction,
      to an almost immediate full implantation. CONCLUSIONS: Modifications of the DBCG
      guidelines were generally well implemented, but the time to full implementation
      varied from less than one year up to around five years. Our data is registry
      based and does not allow a closer analysis of the causes for delay in
      implementation of guideline modifications.

PMID- 29202622
TI  - An inter-observer Ki67 reproducibility study applying two different assessment
      methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast
      cancer cooperative group (DBCG).
AB  - INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of
      pathology to define the intrinsic breast cancer subtypes by application of
      immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a
      specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning
      impaired reproducibility of Ki67 estimation and threshold inconsistency led to
      the initiation of this quality assurance study (2013-2015). The aim of the study
      was to investigate inter-observer variation for Ki67 estimation in malignant
      breast tumors by two different quantification methods (assessment method and
      count method) including measure of agreement between methods. MATERIAL AND
      METHODS: Fourteen experienced breast pathologists from 12 pathology departments
      evaluated 118 slides from a consecutive series of malignant breast tumors. The
      staining interpretation was performed according to both the Danish and Swedish
      guidelines. Reproducibility was quantified by intra-class correlation coefficient
      (ICC) and Lights Kappa with dichotomization of observations at the larger than
      (>) 20% threshold. The agreement between observations by the two quantification
      methods was evaluated by Bland-Altman plot. RESULTS: For the fourteen raters the
      median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by
      the count method. Light's Kappa was 0.664 for observation by the assessment
      method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the
      assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method. CONCLUSION:
      Although the study in general showed a moderate to good inter-observer agreement
      according to both ICC and Lights Kappa, still major discrepancies were identified
      in especially the mid-range of observations. Consequently, for now Ki67
      estimation is not implemented in the DBCG treatment algorithm.

PMID- 29202624
TI  - Breast cancer patient advocacy in Denmark.

PMID- 29202623
TI  - Nonclinical Development of ANX005: A Humanized Anti-C1q Antibody for Treatment of
      Autoimmune and Neurodegenerative Diseases.
AB  - ANX005 is a humanized immunoglobulin G4 recombinant antibody against C1q that
      inhibits its function as the initiating molecule of the classical complement
      cascade. The safety and tolerability of ANX005 are currently being evaluated in a
      phase I trial in healthy volunteers ( www.clinicaltrials.gov Identifier:
      NCT03010046). Inhibition of C1q can be applied therapeutically in a broad
      spectrum of diseases, including acute antibody-mediated autoimmune disease, such
      as Guillain-Barre syndrome (GBS), and in chronic diseases of the central nervous
      system involving complement-mediated neurodegeneration, such as Alzheimer's
      disease (AD). To support the clinical development of ANX005, several studies were
      conducted to assess the pharmacology, pharmacokinetics, and potential toxicity of
      ANX005. ANX-M1, the murine precursor of ANX005, functionally inhibits the
      classical complement cascade both in vitro and in vivo, to protect against
      disease pathology in mouse models of GBS and AD. Toxicology studies with ANX005,
      itself, showed that intravenous administration once weekly for 4 weeks was well
      tolerated in rats and monkeys, with no treatment-related adverse findings. Serum
      levels of ANX005 in monkeys correlate with a reduction in free C1q levels both in
      the serum and in the cerebrospinal fluid. In summary, ANX005 has shown proof of
      concept in in vitro and in vivo nonclinical pharmacology models, with no toxicity
      in the 4-week repeat-dose studies in rats and monkeys. The no observed adverse
      effect level was 200 mg/kg/dose, which is 200-fold higher than the first-in-human
      starting dose of 1 mg/kg in healthy volunteers.

PMID- 29202625
TI  - The relationship between the use of running applications and running-related
      injuries.
AB  - OBJECTIVES: Training errors are suggested to be an important cause of running
      related injuries (RRIs). As most runners train individually, digital coaching
      using running applications is becoming increasingly popular. However, the quality
      of these applications is unknown. The aim of the present cross-sectional study
      was to evaluate the relationship between the use of running applications and
      RRIs. METHODS: An online questionnaire was used to collect data on running
      activities of 1,029 runners, their injuries, and the association between the use
      of running applications and RRIs. Parametric and non-parametric tests for
      independent samples were used to analyze the baseline characteristics of the
      participants. Univariate logistic regression analyses and multiple logistic
      regression analysis (Enter procedure) were used to determine the association
      between the use of running applications and RRIs, while adjusting for confounding
      effects. RESULTS: Of all the 1,029 runners included in this study, 31% (n = 319)
      got injured and 44% (n = 453) used an application in the previous 12 months.
      Multiple logistic regression analysis showed no statistically significant
      association between the use of running applications and RRIs. CONCLUSIONS: Based
      on this study, the use of running applications was not associated with an
      increased or decreased risk of RRIs. Running applications can be used by runners
      without any further implications to guide their training activities. However,
      runners should be aware that the use of predefined running schemes is associated
      with RRI risk. It is important that following a previous RRI, athletes should be
      fully recovered before resuming their training sessions as hindrance from a
      previous RRI is highly associated with the occurrence of a new RRI.

PMID- 29202626
TI  - A Nurse-Led and Teacher-Assisted Adolescent Healthy Weight Program to Improve
      Health Behaviors in the School Setting.
AB  - Adolescents with overweight and obesity are at risk for future health problems.
      The purpose of this study was to examine the feasibility and initial efficacy of
      a weight management intervention to help adolescents develop healthy nutrition
      and physical activity behaviors and improve their anthropometrics. This study
      used a single-group repeated measures design in a small school in Durham, North
      Carolina (NC). The intervention consisted of a nurse-led and teacher-assisted
      nutrition and physical activity education and exercise classes that met twice
      each week for 45-60 minutes for 7 weeks. Data were collected at Time 1
      (baseline), Time 2 (after intervention completion), and Time 3 (after 3 months on
      their own). Interview feedback, low cost, and successful completion of all
      planned activities indicated that all stakeholders found the project beneficial
      and suitable for their school. This study suggests that a weight management
      intervention for adolescents was feasible in the school setting.

PMID- 29202627
TI  - Palliative treatment with carboplatin as late line therapy to patients with
      metastatic breast cancer.

PMID- 29202628
TI  - "I Kinda Feel Like Wonder Woman": An Interpretative Phenomenological Analysis of
      Pole Fitness and Positive Body Image.
AB  - The purpose of this research was to describe and interpret the positive body
      image experiences of women actively engaged in pole fitness. A total of seven
      women between the ages of 20 and 36 years participated in semistructured one-on
      one interviews and follow-up interviews. Participant observation was also used to
      generate data. Data were analyzed using an interpretative phenomenological
      analysis approach, and the positive body image experiences of women are
      represented by five themes: (a) observation and exposure fostering body
      acceptance, (b) performance promoting self-confidence, (c) personal growth and
      sexual expression, (d) unconditional community support creates comfort, and (e)
      body appreciation through physical skill development. Findings suggest that women
      engaging in pole fitness may experience positive body image, and the words of
      participants provide insight into the components of pole fitness that may foster
      positive body image. Pole fitness may provide a unique exercise context whereby
      women can develop and maintain positive body image.

PMID- 29202629
TI  - Adequate Muscular Strength May Help to Reduce Risk of Residual-Specific
      Mortality: Findings From the National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: Muscular strength has been shown to inversely associate with
      mortality. The purpose of this study was to examine the association between
      muscular strength and residual-specific mortality among a national sample of US
      adults, which has yet to be investigated. Here, residual-specific mortality is
      identified as deaths not inclusive of the 9 leading causes of death as identified
      by the International Classification of Diseases, 10th revision. METHODS: Data
      from the 1999-2002 National Health and Nutrition Examination Survey were used (N
      = 2171 adults, aged 50-85 y). Participants were followed through 2011, including
      a median follow-up of 125 months. Lower extremity muscular strength was assessed
      using maximal isokinetic contractions. RESULTS: After adjusting for all
      covariates (age, gender, race/ethnicity, body mass index, C-reactive protein,
      mean arterial pressure, self-report of meeting aerobic-based physical activity
      guidelines, and physician diagnoses of diabetes), the Cox proportional hazard
      model demonstrated that for every 25 N increase in lower extremity muscular
      strength, individuals had a 14% reduced risk of residual-specific death (hazard
      ratio = 0.86; 95% confidence interval, 0.78-0.96; P = .008). CONCLUSION: Lower
      body muscular strength is inversely and independently associated with residual
      specific mortality risk, underscoring the importance of adequate muscular
      strength to prolong survival.

PMID- 29202630
TI  - Concurrent new drug prescriptions and prognosis of early breast cancer: studies
      using the Danish Breast Cancer Group clinical database.
AB  - BACKGROUND: Myriad reports suggest that frequently used prescription drugs alter
      the viability of breast cancer cells in pre-clinical studies. Routine use of
      these drugs, therefore, may impact breast cancer prognosis, and could have
      important implications for public health. METHODS: The Danish Breast Cancer Group
      (DBCG) clinical database provides high-quality prospectively collected data on
      breast cancer diagnosis, treatment, and routine follow-up for breast cancer
      recurrence. Individual-level linkage of DBCG data to other population-based and
      medical registries in Denmark, including the Danish National Prescription
      Registry, has facilitated large population-based pharmacoepidemiology studies. A
      unique advantage of using DBCG data for such studies is the ability to
      investigate the association of drugs with breast cancer recurrence rather than
      breast cancer mortality - which may be misclassified - or all-cause mortality.
      Here we summarize findings from pharmacoepidemiological studies, based on DBCG
      data, on the association between routinely used prescription drugs and risk of
      breast cancer recurrence. RESULTS: Our findings suggest that concurrent use of
      glucocorticoids, ACE inhibitors, aspirin, NSAIDs, selective COX-2 inhibitors,
      digoxin, and opioids has little impact on breast cancer recurrence. Similarly,
      patients who use SSRIs concurrently with tamoxifen treatment are not at increased
      risk of recurrence. In contrast, post-diagnostic use of simvastatin, a lipophilic
      statin, correlates with a decreased risk of breast cancer recurrence, providing a
      rationale for a prospective randomized clinical trial investigating simvastatin
      as an adjuvant therapy for breast cancer. CONCLUSION: As a whole, findings of
      pharmacoepidemiological studies based on DBCG data provide reassurance to
      physicians and healthcare personnel who provide supportive care during and after
      cancer (including prescriptions for comedications) and to breast cancer survivors
      for whom the risk of breast cancer recurrence is a major concern.

PMID- 29202631
TI  - Vaping medical marijuana.

PMID- 29202632
TI  - Lower age increases the risk of revision for stemmed and resurfacing shoulder
      hemi arthroplasty.
AB  - Background and purpose - The number of patients where shoulder hemiarthroplasty
      (SHA) is an option is still substantial. Descriptive analyses performed by the
      Swedish Shoulder Arthroplasty Registry (SSAR) showed that while patients
      receiving SHA designs, i.e. resurfacing hemi (RH) and stemmed hemi (SH), reported
      similar shoulder functionality and quality of life, the revision rate for RH
      (12%) was larger than for SH (6.7%); this difference was studied. Patients and
      methods - All primary SHA (n = 1,140) for OA reported to SSAR between 1999 and
      2009 were analyzed regarding risk factors for revision and PROM outcome, 950
      shoulders with primary OA (POA), and 190 secondary OA (SOA). Mean age was 67.4
      years (SD 10.8). PROM including WOOS and EQ-5D were collected at 5 years, until
      December 31, 2014. Results - 76/950 prostheses because of POA and 16/190
      prosthesis because of SOA were revised. Age at primary surgery was the main
      factor that influenced the risk of revision, lower age increased the risk of
      revision, and was also the explanation for the difference between SH and RH. We
      also found that SH and RH had similar outcomes measured by PROM, but the POA
      group had higher scores than the SOA group with a clinically relevant difference
      of 10% in WOOS. Interpretation - The risk of revision for SH and RH is similar
      when adjusted for age and does not depend on primary diagnosis or sex. A lower
      age increases the risk of revision. Patients suffering from POA experience better
      shoulder functionality than SOA patients irrespective of implant type.

PMID- 29202633
TI  - Arthroscopic management of posterior instability of the shoulder: A systematic
      review of predictive factors associated with poorer surgical outcomes.
AB  - INTRODUCTION: We aimed to perform a systematic review to identify factors that
      may lead to poorer outcomes in arthroscopic surgery for posterior shoulder
      instability. METHODS: We searched MEDLINE, Embase and the Cochrane Database of
      Systematic Reviews for 757 unique articles. We eventually included 22 articles.
      Data were analysed using Review Manager 5.3. RESULTS: The presence of chondral
      damage was associated with poorer outcomes as reflected in a higher post
      operative Quick Disabilities of theArm, Shoulder and Hand score (mean difference
      (MD) = 17.1; 95% confidence interval (CI) = 2.82-31.4; p = 0.02), higher
      WesternOntario Shoulder Instability (WOSI) index (MD = 468.0; 95% CI = 136.5
      799.5; p = 0.006), lower Simple Shoulder Test score (MD = -2.40; 95% CI = -4.34
      to -0.46; p = 0.02) and a lower Single Assessment Numeric Evaluation score (MD = 
      15.4; 95% CI = -30.6 to -0.23; p = 0.05). The presence of previous shoulder
      surgery was associated with poorer outcomes as depicted by a lower American
      Shoulder and Elbow Society (ASES) score (MD = -93.1; 95% CI = -96.9 to -89.3; p <
      0.0001). The availability of workers' compensation was associated with poorer
      outcomes as revealed by a lower rate of return to work (odds ratio (OR) = 0.02;
      95% CI = 0.00-0.20; p = 0.0008). The presence of additional procedures while
      performing surgery for posterior shoulder instability was associated with poorer
      outcomes as reflected by lower ASES scores (MD = -6.70; 95% CI = -8.64 to -4.76;
      p < 0.0001), higher WOSI index (MD = 63.4; 95% CI = 33.0-93.8; p < 0.0001), lower
      University of California at Los Angeles (UCLA) scores (MD = -2.30; 95% CI = -2.81
      to -1.79; p < 0.0001), higher pain scores (MD = 0.72; 95% CI = 0.39-1.05; p <
      0.0001) and higher post-operative instability (MD = 0.80; 95% CI = 0.57-1.03; p <
      0.0001). CONCLUSION: The presence of chondral damage, previous shoulder surgery,
      concomitant surgery and workman's compensation was associated with poorer
      outcomes for arthroscopic repair of posterior shoulder instability. Further
      studies should be done to further validate these factors.

PMID- 29202634
TI  - Energy Cost of Common Physical Activities in Preschoolers.
AB  - BACKGROUND: To determine the energy cost of common physical activities in
      preschoolers and to compare it with the Compendium of Energy Expenditure for
      Youth (CEEY). METHODS: In total, 42 children [age: 4.8 (0.8) y; body mass index:
      15.3 (2.0) kg/m2; 22 boys] completed 13 common physical activities covering
      sedentary to vigorous intensities, while energy expenditure (EE) was measured
      continuously by indirect calorimetry. Activity-specific metabolic equivalents
      (AME) were calculated as the EE observed during each single activity divided by
      the EE during observed rest. Independent t tests were applied to analyze
      differences between boys and girls and between AME and CEEY. RESULTS: No
      significant differences in AME were observed between girls and boys. Except for
      playing hide-and-seek, all indoor activities revealed significantly higher energy
      costs compared with those stated in the compendium. Significant differences in
      outdoor activities were found for riding a tricycle [5.67 (95% confidence
      interval, 4.94-6.4) AME vs 6.2 metabolic equivalents, riding a bike, P < .05] and
      for fast walking [5.42 (95% confidence interval, 4.84-6.0) AME vs 4.6 metabolic
      equivalents, P < .05]. CONCLUSIONS: Applying the CEEY to preschoolers will lead
      to a substantial underestimation of EE. Therefore, we recommend that a CEEY for
      preschool children be developed if measurement of EE is not feasible.

PMID- 29202635
TI  - The coupled effect of nucleosome organization on gene transcription level and
      transcriptional plasticity.
AB  - Nucleosomes are the fundamental units of eukaryotic chromatin and can modulate
      the DNA accessibility for transcriptional regulatory elements. Many studies have
      demonstrated the effect of nucleosome organization on gene transcription level
      and transcriptional plasticity upon different conditions. Our recent study showed
      that nucleosome organization also plays an important role in modulating the
      plasticity of gene transcriptional status in maize. Here, we integrated our
      findings with previous studies on the role of nucleosome organization in
      regulation of gene transcription. We highlighted our recent finding that
      nucleosome organization plays an important role in determining the plasticity of
      gene transcription, beyond its role in regulating gene transcription level,
      particularly for intrinsically DNA-encoded nucleosome organization. We also
      discussed the features of sequence and structure of genes involved in affecting
      nucleosome organization around genes, as well as the potential mechanisms for
      overcoming the coupled effect of nucleosome organization on gene transcription
      level and transcriptional plasticity.

PMID- 29202636
TI  - Range of motion and ankle injury history association with sex in pediatric and
      adolescent athletes.
AB  - BACKGROUND: Ankle sprain is one of the most common musculoskeletal injuries among
      young athletes, and there remains a gap in the literature regarding
      susceptibility to such injuries among physically active youth. OBJECTIVE: The
      primary purpose of this study was to determine the associations between sex, a
      history of ankle sprain, and ankle range of motion (ROM) in pediatric and
      adolescent athletes. METHODS: Athletes under the age of 18 years old who
      presented to a sports injury prevention center underwent ankle ROM measurements
      including plantarflexion (PF), inversion (IV), and eversion (EV). A two-way
      analysis of covariance (ANCOVA) was performed to examine effect of sex and a
      history of ankle sprain on ROMs. Also, a binary logistic regression was performed
      to investigate variables that are associated with a history of ankle injury.
      RESULTS: Among 452 pediatric and adolescent athletes [268 females (13.6 +/- 2.3
      years old) and 184 males (13.3 +/- 2.5 years old)], 128 reported a history of
      previous ankle sprain. Females demonstrated significantly increased ROMs (PF and
      IV bilaterally, and right EV) compared to males while there was no effect of a
      history of ankle sprain on ROMs. Female sex was independently associated with a
      history of ankle sprain. CONCLUSION: There was a strong effect of female sex on
      ROMs rather than a history of ankle injury history. Additionally, pediatric and
      adolescent females have greater odds of a history of ankle sprain when compared
      to their male counterparts.

PMID- 29202637
TI  - Methods for Handling Unobserved Covariates in a Bayesian Update of a Cost
      effectiveness Model.
AB  - Health economic decision models often involve a wide-ranging and complicated
      synthesis of evidence from a number of sources, making design and implementation
      of such models resource-heavy. When new data become available and reassessment of
      treatment recommendations is warranted, it may be more efficient to perform a
      Bayesian update of an existing model than to construct a new model. If the
      existing model depends on many, possibly correlated, covariates, then an update
      may produce biased estimates of model parameters if some of these covariates are
      completely absent from the new data. Motivated by the need to update a cost
      effectiveness analysis comparing diagnostic strategies for coronary heart
      disease, this study develops methods to overcome this obstacle by either
      introducing additional data or using results from previous studies. We outline a
      framework to handle unobserved covariates, and use our motivating example to
      illustrate both the flexibility of the proposed methods and some potential
      difficulties in applying them.

PMID- 29202638
TI  - A Systematic Scoping Review of Engagement in Physical Activity Among LGBTQ+
      Adults.
AB  - BACKGROUND: LGBTQ+ (lesbian, gay, bisexual, transgender, queer, etc) persons are
      subject to elevated rates of chronic diseases and health concerns that can be
      addressed through regular participation in physical activity. However, LGBTQ+
      adults experience unique challenges to engaging in physical activity.
      Subsequently, the aim of this study is to describe the dominant narratives
      related to the complex intersection of sexual orientation, gender identity, and
      physical activity. METHODS: A systematic search and scoping review of existing
      literature was conducted in June 2016. Studies were identified by searching 9
      electronic databases. Data were then extracted, summarized, and organized by
      LGBTQ+ subgroups. Conceptual maps of prominent narratives were created. RESULTS:
      Separate narratives were identified for sexual minority men and women. The
      dominant trend for sexual minority men was increased physical activity levels,
      often motivated by a perceived body ideal of being thin and/or muscular. The
      dominant trend for sexual minority women was decreased physical activity levels,
      predicated on a social norm that emphasizes bodily acceptance. CONCLUSIONS:
      Sexual orientation affects engagement in physical activity differentially by
      gender. Our findings suggest that physical activity interventions should be
      targeted to unique subgroups of the LGBTQ+ population.

PMID- 29202639
TI  - Emotional responding in NSSI: examinations of appraisals of positive and negative
      emotional stimuli, with and without acute stress.
AB  - Non-suicidal self-injury (NSSI) is commonly used by young adults to regulate
      emotional responses. Yet, experimental examination of how people who self-injure
      appraise and respond to emotional stimuli is limited. We examined appraisals of,
      and responses to, emotive images in young adults who did and did not self-injure,
      and assessed whether these were impacted by exposure to a stressor. Study 1 (N =
      51) examined whether participants differed in their appraisals of emotional
      images. Study 2 (N = 78) assessed whether appraisals of images changed after
      exposure to the Trier Social Stress Test. Ratings of emotional valence and
      arousal were collected in both studies; skin conductance was measured as an
      indicator of physiological arousal in Study 2. In Study 1 participants reporting
      NSSI rated positively valenced images as less pleasant than participants not
      reporting NSSI. In Study 2, after acute stress, participants reporting NSSI
      displayed dampened physiological reactions to positive images whereas
      participants who did not self-injure displayed heightened physiological reactions
      to these and rated them as more pleasant. Individuals who self-injure seem less
      able to engage in strategic mood repair after exposure to stress compared to
      people who do not self-injure.

PMID- 29202640
TI  - A Comparative Assessment of Implant Site Viability in Humans and Rats.
AB  - Our long-term objective is to devise methods to improve osteotomy site
      preparation and, in doing so, facilitate implant osseointegration. As a first
      step in this process, we developed a standardized oral osteotomy model in
      ovariectomized rats. There were 2 unique features to this model: first, the rats
      exhibited an osteopenic phenotype, reminiscent of the bone health that has been
      reported for the average dental implant patient population. Second, osteotomies
      were produced in healed tooth extraction sites and therefore represented the
      placement of most implants in patients. Commercially available drills were then
      used to produce osteotomies in a patient cohort and in the rat model. Molecular,
      cellular, and histologic analyses demonstrated a close alignment between the
      responses of human and rodent alveolar bone to osteotomy site preparation. Most
      notably in both patients and rats, all drilling tools created a zone of dead and
      dying osteocytes around the osteotomy. In rat tissues, which could be collected
      at multiple time points after osteotomy, the fate of the dead alveolar bone was
      followed. Over the course of a week, osteoclast activity was responsible for
      resorbing the necrotic bone, which in turn stimulated the deposition of a new
      bone matrix by osteoblasts. Collectively, these analyses support the use of an
      ovariectomy surgery rat model to gain insights into the response of human bone to
      osteotomy site preparation. The data also suggest that reducing the zone of
      osteocyte death will improve osteotomy site viability, leading to faster new bone
      formation around implants.

PMID- 29202642
TI  - Physical Activity Barriers and Facilitators Among US Pacific Islanders and the
      Feasibility of Using Mobile Technologies for Intervention: A Focus Group Study
      With Tongan Americans.
AB  - BACKGROUND: Pacific Islanders experience an elevated risk of health conditions
      such as obesity and diabetes, which are related to a lack of physical activity
      (PA). However, little attention has been paid to understanding the determinants
      of PA and promoting PA among this racial/ethnic group in the United States.
      METHODS: We conducted focus group discussions with Tongan Americans, one of the
      major Pacific Islander groups in the United States, to gain a better
      understanding of their PA participation patterns, their barriers and
      facilitators, their attitudes toward PA, and their perceptions of how mobile
      technologies such as smartphones could help increase their PA levels. RESULTS:
      Results indicate that although the participants understand the various benefits
      of PA, they do not engage in much leisure-time PA for exercise purposes. A lack
      of time is cited as an important reason for insufficient PA participation. In
      addition, most participants report familiarity with smartphones, positive views
      of mobile technology, and interest in using smartphones to measure and promote
      PA. CONCLUSION: Multiple barriers were related with the low level of PA among
      Tongan Americans. Mobile technology is a promising way of enhancing PA among
      Tongan Americans and potentially other Pacific Islander subgroups. Culturally
      tailored strategies could significantly enhance the effectiveness of PA
      intervention.

PMID- 29202641
TI  - The management and survival outcomes of nasopharyngeal cancer in the Nordic
      countries<sup/>.

PMID- 29202643
TI  - Factor Structure of Responses to the Portuguese Version of Questions About Screen
      Time-Based Sedentary Behavior Among Adolescents.
AB  - BACKGROUND: This study aimed to examine the factor structure of responses to the
      Portuguese version of questions related to screen time-based sedentary behavior
      among adolescents. METHODS: This cross-sectional study with a sample of 1083
      adolescents aged 14-19 years was conducted in Brazil. The sample was randomly
      divided into 2 groups for an exploratory factor analysis and for a confirmatory
      factor analysis. Screen time was investigated by a Portuguese version of
      questions about time sitting in front of television, computer, and video games on
      weekdays and weekends. RESULTS: Scree plots showed 2 factors with eigenvalues
      above 1. One factor was formed by items about television and computer use, and
      the other factor was formed by items about video game use. The exploratory factor
      analysis with 2 factors resulted in factor loadings above .60. A second model
      with 1 factor was estimated and resulted in factor loadings above .55. A
      confirmatory factor analysis was estimated based on the 2-factor exploratory
      factor analysis and goodness-of-fit statistics were adequate. Confirmatory factor
      analysis with 1 factor had goodness-of-fit statistics adequate. CONCLUSIONS: The
      Portuguese language version of self-report screen time had 2 possible factor
      solutions, and items demonstrated good factor structure with reasonable
      reliability making it suitable for use in the future studies.

PMID- 29202644
TI  - Outpatient total hip and knee arthroplasty.
AB  - As a result of the introduction of fast-track programs, the length of hospital
      stay after arthroplasty has decreased to a point where some patients meet the
      discharge criteria on the day of surgery. In several studies, well-established
      fast-track centers have demonstrated the feasibility of outpatient procedures in
      selected patients. However, in literature the term "outpatient" is sometimes also
      used for patients who spend one or more nights in hospital. We therefore propose
      to use "outpatient" solely for patients who are discharged to their own home on
      the day of surgery and do not have an overnight stay at either the hospital or
      another non-home facility. Also, several challenges need to be overcome before
      this becomes an established procedure. The combination of preoperative high-dose
      steroids and multimodal opioid-sparing analgesia has enhanced patient recovery
      after arthroplasty, but efforts to control undesirable pathophysiological
      responses will be a prerequisite to improve the success rate of an outpatient
      setting. Also, care must be taken to avoid extra activities or investments solely
      to enable discharge on the day of surgery. Further cost analyses will have to be
      performed to establish the true financial benefit of outpatient treatment.

PMID- 29202645
TI  - Influence of specific comorbidities on survival after early-stage breast cancer.
AB  - BACKGROUND: While comorbidity indices are useful for describing trends in
      survival, information on specific comorbidities is needed for the clinician
      advising the individual breast cancer patient on her treatment. Here we present
      an analysis of overall survival, breast cancer-specific mortality, and effect of
      medical adjuvant treatment among breast cancer patients suffering from 12 major
      comorbidities compared with breast cancer patients without comorbidities.
      MATERIAL AND METHODS: The study population was identified from the Danish Breast
      Cancer Cooperative Group and included 59,673 women without prior cancer diagnosed
      with early-stage breast cancer in Denmark from 1990 to 2008 with an estimated
      median potential follow-up of 14 years and 10 months. Information on comorbidity
      and causes of death was derived from population-based registries. Multivariable
      proportional hazards regression models were used to assess the effect of
      comorbidities on mortality, all-cause and breast cancer specific, using patients
      without comorbidity as reference. RESULTS: At breast cancer diagnosis, 16% of
      patients had comorbidities and 84% did not. Compared with the latter, the risk of
      dying from all causes was significantly increased for all types of comorbidity,
      but the risk of dying from breast cancer was significantly increased only for
      peripheral vascular disease, dementia, chronic pulmonary disease, liver, and
      renal diseases. Comorbidities diagnosed within 5 years of breast cancer diagnosis
      correlated with a greater risk of dying than comorbidities diagnosed more than 5
      years before breast cancer diagnosis. With a few exceptions, the effect of
      adjuvant treatment on breast cancer mortality was similar among patients with and
      without comorbidity. CONCLUSION: Breast cancer mortality was not significantly
      elevated for patients with prior myocardial infarction, congestive heart failure,
      cerebrovascular disease, connective tissue disease, ulcer disease, and diabetes.
      The similar effect of adjuvant treatment in patients with and without comorbidity
      underlines the importance of adhering to guideline therapy.

PMID- 29202646
TI  - Submucosal Diclofenac for Acute Postoperative Pain in Third Molar Surgery: A
      Randomized, Controlled Clinical Trial.
AB  - Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID)
      for relief of inflammatory pain. A recent formulation combines this drug with
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) to improve its solubility and to
      enable subcutaneous administration. Previous studies confirmed the efficacy of
      this combination. This study's aim was to evaluate the efficacy, safety, and
      local tolerability of diclofenac HPbetaCD administered as a local submucosal
      injection prior to lower third molar surgery. We conducted a prospective,
      randomized, double-blind, placebo-controlled, parallel-group phase II single
      center study. Seventy-five patients requiring mandibular third molar surgery were
      randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPbetaCD, 12.5 mg/1 mL
      diclofenac HPbetaCD, 25 mg/1 mL diclofenac HPbetaCD, 50 mg/1 mL diclofenac
      HPbetaCD, or 1 mL placebo. The respective study drug was injected into the
      mucosal tissue surrounding the surgical site prior to surgery following
      achievement of local anesthesia. The primary outcome measure was the area under
      the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery.
      This demonstrated a global treatment effect between the active groups and
      placebo, hence confirming the study drug's efficacy ( P = 0.0126). Secondary
      outcome measures included the time until onset of pain and the time until
      patients required rescue medication, both showing statistical significance of the
      study drug compared to placebo ( P < 0.0161 and P < 0.0001, respectively). The
      time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac
      HPbetaCD) and 16 h (for 50 mg/1 mL diclofenac HPbetaCD). Interestingly, the 5
      mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions
      (time until rescue medication = 12.44 h). A total of 14% of patients experienced
      minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis.
      These resolved without further intervention. The study results overall indicate
      efficacy, safety, and relative tolerability of diclofenac HPbetaCD used locally
      as a submucosal injection prior to third molar surgery (ClinicalTrials.gov
      NCT01706588).

PMID- 29202647
TI  - Swallow presyncope in an athletic patient caused by third-degree atrioventricular
      block.
AB  - Introduction Swallow syncope is a neurally mediated syncope. Multiple causes have
      been described in literature. A rare cause is arrhythmias. Only a limited amount
      of cases present the association of swallow syncope and third degree AV-block.
      Case presentation A 39-year-old man presented with episodes of presyncope while
      eating. Further medical history, physical examination, resting 12-lead ECG, cyclo
      ergometry, transthoracic echocardiography and MRI of the heart were normal. 24 h
      Holter monitoring demonstrated high-grade third-degree atrioventricular (AV)
      block. The patient was scheduled for pacemaker implantation. Discussion
      Arrhythmia is a rare cause of swallow syncope. Reported arrhythmic causes are
      sinus bradycardia, sinoatrial block, atrioventricular block and complete atrial
      and ventricular asystole. Essential to the diagnosis is that (pre)syncope is
      preceded by swallowing and documentation of AV block on 24 h Holter monitoring.
      Treatment is guided by ESC guidelines which state that reflex syncope has a grade
      IIa recommendation for pacing, while current evidence suggests that asymptomatic
      vagally mediated AV block should not be treated until symptomatic.

PMID- 29202648
TI  - An algorithm to improve outcomes of radial forearm flap donor site.
AB  - : Abstarct Background: Due to the high rate of donor site complications the
      Radial Forearm Flap (RFF) has lost ground in favor of the Antero-lateral tight
      flap (ALT) and other flaps. We have designed a reconstruction algorithm for
      reconstruction of its donor site. The goal of this study was to retrospectively
      evaluate the impact of this algorithm on RFF donor site complication rates.
      METHODS: The authors analyzed retrospectively 31 patients who underwent free
      radial forearm flap reconstruction between November 2009 and May 2013. Donor site
      complications were compared with data from patients treated before introdutction
      of the algorithm. Within the group were compared patients in which the flap was
      harvested suprafascial with those in which the flap was harvested as subfascial.
      RESULTS: Before application of the algorithm, there was a 23.3% complication rate
      at the RFF donor site, in our experience. After introduction of the algorithm,
      complication rate has dropped to 3.2%, consisting in a partial skin graft
      necrosis treated by local wound-care and healed without further intervention.
      CONCLUSIONS: Application of the algorithm described has led to a significant
      reduction in RFF donor site complication rates. This demonstrates that if flap
      donor sites are analyzed and tailor treated in the same way as primary defects
      are, instead of being given secondary importance and just grafted, outcomes
      improve.

PMID- 29202649
TI  - The 'end of AIDS' project: Mobilising evidence, bureaucracy, and big data for a
      final biomedical triumph over AIDS.
AB  - Efforts are currently underway by major orchestrators and funders of the global
      AIDS response to realise the vision of achieving an end to AIDS by 2030. Unlike
      previous efforts to provide policy guidance or to encourage 'best practice'
      approaches for combatting AIDS, the end of AIDS project involves the promotion of
      a clear set of targets, tools, and interventions for a final biomedical solution
      to the epidemic. In this paper, we examine the bureaucratic procedures of one
      major AIDS funder that helped to foster a common vision and mission amongst a
      global AIDS community with widely divergent views on how best to address the
      epidemic. We focus on the methods, movements, and materials that are central to
      the project of ending AIDS, including those related to biomedical forms of
      evidence and big data science. We argue that these approaches have limitations
      and social scientists need to pay close attention to the end of AIDS project,
      particularly in contexts where clinical interventions might transform clinical
      outcomes, but where the social, economic, and cultural determinants of HIV and
      AIDS remain largely intact and increasingly obscured.

PMID- 29202650
TI  - Increasing the Elective Endovascular to Open Repair Ratio of Popliteal Artery
      Aneurysm.
AB  - BACKGROUND: Open repair (OR) for popliteal artery aneurysm (PAA) has recently
      been challenged by endovascular repair (ER) as the primary choice of treatment.
      The aim of the present study was to evaluate time trends in treatment modality
      and compare outcomes between OR and ER among electively operated patients after
      start of screening in 2010 for abdominal aortic aneurysm (AAA), a disease highly
      associated with PAA. METHODS: Between January 1, 2009, and April 30, 2017, 102
      procedures and 36 acute and 66 elective repairs for PAA were identified. RESULTS:
      Over time, a trend ( P = .089) for an increasing elective to acute repair ratio
      of PAA and an increase in elective ER to OR ratio ( P = .003) was found. Among
      electively repaired PAAs, the ER group was older ( P = .047) and had a higher
      ankle-brachial index (ABI; P = .044). The ER group had fewer wound infections ( P
      = .003), fewer major bleeding complications ( P = .046), and shorter in-hospital
      stay ( P < .001). After 1 year of follow-up, the ER group had a higher rate of
      major amputations ( P = .037). Amputation-free survival at the end of follow-up
      did not differ between groups ( P = .68). Among the 17 patients with PAA eligible
      for AAA screening, 4 (24%) were diagnosed with PAA through the screening program
      of AAA. CONCLUSION: The epidemiology of elective repair of PAA has changed toward
      increased ER, although ER showed a higher rate of major amputations at 1 year.
      Confounding was considerable and a randomized trial is needed for evaluation of
      the best therapeutic option.

PMID- 29202651
TI  - Why equity in health and in access to health care are elusive: Insights from
      Canada and South Africa.
AB  - Health and access to health care vary strikingly across the globe, and debates
      about this have been pervasive and controversial. Some comparative data in Canada
      and South Africa illustrate the complexity of achieving greater equity anywhere,
      even in a wealthy country like Canada. Potential bi-directional lessons relevant
      both to local and global public health are identified. Both countries should
      consider the implications of lost opportunity costs associated with lack of
      explicit resource allocation policies. While National Health Insurance is
      attractive politically, Canada's example cannot be fully emulated in South
      Africa. Short- and medium-term attempts to improve equity in middle-income
      countries should focus on equitable access to insurance to cover primary health
      care and on making more use of nurse practitioners and community health workers.
      In the longer-term, attention is needed to the economic and political power
      structures that influence health and health care and that ignore the social and
      societal determinants of sustainable good health locally and globally. This long
      term vision of health is needed globally to achieve improvements in individual
      and population health in a century characterised by limits to economic growth,
      widening disparities, continuing conflict and migration on a large scale and
      multiple adverse impacts of climate change.

PMID- 29202652
TI  - Corrigendum.

PMID- 29202653
TI  - Empathic Concern and the Desire to Help as Separable Components of Compassionate
      Responding.
AB  - When do people experience versus regulate responses to compassion-evoking
      stimuli? We hypothesized that compassionate responding is composed of two factors
      empathic concern and the desire to help-and that these would be differentially
      affected by perspective taking and self-affirmation. Exploratory (Study 1) and
      confirmatory (Study 2) factor analyses indicated that a compassion measure
      consisted of two factors corresponding to empathic concern and the desire to
      help. In Study 1 ( N = 237), participants with high emotion regulation ability
      reported less empathic concern for multiple children than for one, but
      perspective taking prevented this effect. In Study 2 ( N = 155), participants
      reported less desire to help multiple children, but only in the presence of self
      affirmation. In both the studies, empathic concern predicted greater distress
      while the desire to help predicted greater chances of donating. Compassionate
      responding may consist of two separable facets that collapse under distinct
      conditions and that predict distinct outcomes.

PMID- 29202654
TI  - Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life
      Depression and Cognitive Decline.
AB  - Recent research has linked age-related hearing loss to impaired performance
      across cognitive domains and increased risk for dementia diagnosis. The data
      linking hearing impairment to incident late-life depression are more mixed but
      suggest that diminished hearing does increase risk for depression. Behavioral
      mechanisms may explain these associations, such as the withdrawal of older adults
      from situations in which they may have difficulty hearing and communicating,
      which may contribute to the development of social isolation, loneliness, and
      consequent cognitive decline and depression. At a neural level, chronic hearing
      loss leads to reduced activation in central auditory pathways, resulting in
      compensatory increased activation in the cognitive control network, dysfunctional
      auditory-limbic connectivity, and deafferentation-induced atrophy in frontal
      brain regions. These pathologic changes decrease cognitive performance and
      increase depression risk by reducing cognitive reserve, increasing executive
      dysfunction, and disrupting normative emotion reactivity and regulation. Based on
      the available data and informed by this model, evidence-based suggestions are
      proposed for clinicians treating older adults, and a research agenda is advanced
      to facilitate the development of rationally designed and age-appropriate
      psychiatric treatments for older adults with age-related hearing loss. First and
      foremost, treating hearing loss should be investigated as a means of improving
      cognitive and depressive outcomes in well-designed studies incorporating
      comprehensive psychiatric assessments, randomization, objective documentation of
      compliance, and analyses of treatment mediators that will facilitate further
      therapeutic development. Multimodal neuroimaging studies integrating audiometric,
      neuropsychological, and clinical assessments also are needed to further evaluate
      the model proposed. [AJP at 175: Remembering Our Past As We Envision Our Future
      April 1995: Effect of Hearing Enhancement on Medical Status Ratings Twenty-one
      elderly psychiatric patients had lower levels of psychopathology when assessed
      while wearing hearing aids. (Am J Psychiatry 1995; 152:629-631 )].

PMID- 29202656
TI  - Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in
      Schizophrenia.
AB  - OBJECTIVE: Although patients with schizophrenia exhibit impaired suppression of
      the P50 event-related brain potential in response to the second of two identical
      auditory stimuli during a paired-stimulus paradigm, uncertainty remains over
      whether this deficit in inhibitory gating of auditory sensory processes has
      relevance for patients' clinical symptoms or cognitive performance. The authors
      examined associations between P50 suppression deficits and several core features
      of schizophrenia to address this gap. METHOD: P50 was recorded from 52 patients
      with schizophrenia and 41 healthy comparison subjects during a standard auditory
      paired-stimulus task. Clinical symptoms were assessed with the Scale for the
      Assessment of Positive Symptoms and the Scale for the Assessment of Negative
      Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure
      cognitive performance in a subsample of 39 patients. Correlation and regression
      analyses were conducted to examine P50 suppression in relation to clinical
      symptom and cognitive performance measures. RESULTS: Schizophrenia patients
      demonstrated a deficit in P50 suppression when compared with healthy subjects,
      replicating prior research. Within the patient sample, impaired P50 suppression
      covaried reliably with greater difficulties in attention, poorer working memory,
      and reduced processing speed. CONCLUSIONS: Impaired suppression of auditory
      stimuli was associated with core pathological features of schizophrenia,
      increasing confidence that P50 inhibitory processing can inform the development
      of interventions that target cognitive impairments in this chronic and
      debilitating mental illness.

PMID- 29202657
TI  - A case of gastric cancer metastasis to the breast in a female with BRCA2 germline
      mutation and literature review.
AB  - INTRODUCTION: Gastric cancer is a deadly disease. Common sites of distant
      metastasis of gastric cancer are the peritoneum, liver, lymph nodes, and lung.
      The breast is a rare site of metastasis in gastric cancer which occurs in males
      dominantly. PATIENTS AND METHODS: Here, we report the first case of metastatic
      gastric cancer to the breast in a patient with the breast cancer 2 (BRCA2)
      germline mutation. A 34-year-old female was admitted to the hospital with
      dyspepsia and a palpable mass in the left breast. Gastric cancer was confirmed to
      be signet ring cell adenocarcinoma. The breast mass exhibited histological
      properties consistent with gastric cancer. Immunohistochemistry results showed
      the breast tumor was CDX-2 and CK20-positive, but ER-, CK7-, and GATA3-negative.
      The BRCA1 gene had a wild-type sequence, but a heterozygous variant was
      discovered in BRCA2 in exon 10 (c.1744A > C, p.T582P); the significance of this
      variant is unknown. RESULTS: The patient received palliative XELOX (capecitabine
      + oxaliplatin) with radiation therapy to the stomach. The breast tumor resolved
      completely, but the overall response was partial. CONCLUSION: Gastric cancer
      metastasis to the breast is rare, but should be considered in young female
      patients with signet ring cell type gastric cancer.

PMID- 29202655
TI  - Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A
      Midazolam-Controlled Randomized Clinical Trial.
AB  - OBJECTIVE: Pharmacotherapy to rapidly relieve suicidal ideation in depression may
      reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine
      treatment has mostly been studied in patients with low levels of suicidal
      ideation. The authors tested the acute effect of adjunctive subanesthetic
      intravenous ketamine on clinically significant suicidal ideation in patients with
      major depressive disorder. METHOD: In a randomized clinical trial, adults (N=80)
      with current major depressive disorder and a score >=4 on the Scale for Suicidal
      Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were
      randomly assigned to receive ketamine or midazolam infusion. The primary outcome
      measure was SSI score 24 hours after infusion (at day 1). RESULTS: The reduction
      in SSI score at day 1 was 4.96 points greater for the ketamine group compared
      with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of
      responders (defined as having a reduction >=50% in SSI score) at day 1 was 55%
      for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95%
      CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood
      States depression subscale was greater at day 1 for the ketamine group compared
      with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect
      mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived,
      and clinical improvement was maintained for up to 6 weeks with additional
      optimized standard pharmacotherapy in an uncontrolled follow-up. CONCLUSIONS:
      Adjunctive ketamine demonstrated a greater reduction in clinically significant
      suicidal ideation in depressed patients within 24 hours compared with midazolam,
      partially independently of antidepressant effect.

PMID- 29202660
TI  - Abstracts of the 27th meeting of the Belgian Endocrine Society.

PMID- 29202658
TI  - Ambroise Pare (1510-1590) and His Innovative Work on the Treatment of War
      Injuries.
AB  - The purpose of this study is to summarize the innovations of Ambroise Pare (1510
      1590) on the treatment of war wounds and improving amputation technique through
      ligature in arteries and veins. Ambroise Pare debunked the widely accepted idea
      that gun powder was poisonous for wounds. He also minimized the use of cautery of
      wounds by his dressing methods and the application of ligature during
      amputations. All these innovative rationales revolutionized the practice of war
      surgery during the Renaissance and paved the way for the introduction of modern
      surgery. Nevertheless, although his wound dressing innovations became widely
      accepted, the same did not happen with ligature and amputation; those techniques
      could become widely applicable if one could somehow control bleeding until the
      blood vessels had been tied. This became possible much later in the 18th century
      when Jean Louis Petit invented the first useful and efficient tourniquet.

PMID- 29202659
TI  - The Cost of Caring: Economic Vulnerability, Serious Emotional Distress, and Poor
      Health Behaviors Among Paid and Unpaid Family and Friend Caregivers.
AB  - This study examined differences between paid and unpaid family/friend caregivers
      to better understand the consumer-driven caregiving workforce. We compared
      economic vulnerability, unhealthy behavior, and serious emotional distress for
      475 paid and 10,500 unpaid family/friend informal caregivers from the 2009
      California Health Interview Survey. We then estimated whether caregiver status
      moderated the relationship between economic vulnerability and health outcomes.
      Compared to unpaid family/friend caregivers, paid family/friend caregivers had a
      27% greater risk ( p = .002) of economic vulnerability. Among all family/friend
      caregivers, the probabilities of serious emotional distress and unhealthy
      behaviors increased by >100% and 28% for those with the greatest compared to the
      least economic vulnerability, and caregiver type did not moderate these
      relationships. To address economic and health vulnerabilities of paid informal
      caregivers, policy makers might increase wages in consumer-driven programs. These
      changes could prove beneficial to both paid informal caregivers and their care
      recipients, while reducing long-term inefficiencies in consumer-driven programs.

PMID- 29202661
TI  - Effects of backpack load and positioning on nonlinear gait features in young
      adults.
AB  - Overloaded backpacks can cause changes in posture and gait dynamic balance.
      Therefore, the aim of this study was to assess gait regularity and local dynamic
      stability in young adults as they carried a backpack in different positions, and
      with different loads. Twenty-one healthy young adults participated in the study,
      carrying a backpack that was loaded with 10 and 20% of their body weight (BW).
      The participants walked on a level treadmill at their preferred walking speeds
      for 4 min under different conditions of backpack load and position (i.e. with
      backpack positioned back bilaterally, back unilaterally, frontally or without a
      backpack). Results indicate that backpack load and positioning significantly
      influence gait stability and regularity, with the exception of the 10% BW
      bilateral back position. Therefore, the recommended safe load for school-age
      children and adolescents (10% of BW) should also be considered for young adults.
      Practitioner summary: Increase in load results in changes in posture, muscle
      activity and gait parameters, so we investigated the gait adaptations related to
      regularity and stability. Conditions with high backpack loads significantly
      influenced gait stability and regularity in a position-dependent manner, except
      for 10% body weight bilateral back position.

PMID- 29202662
TI  - Addressing Mental Health Needs of Refugees.
AB  - Throughout history, refugees have alternatively been seen as entitled victims of
      adversity or as threats or abusers of host countries scarce resources. Within the
      present globalized context, ambivalent public perceptions of refugees are
      shattering the protective nature of the post migratory environment in refugee
      receiving countries. This raises new challenges for refugees' mental health and
      calls for systemic responses to address both pre-migratory trauma and losses and
      post migratory adversities. Recent evidence on the effectiveness of mental health
      treatment for refugees confirms the utility of trauma-focused psychotherapy and
      the limits of psychopharmacology for stress related disorders in this group.
      Training of mental health professionals may improve the quality of care for
      refugees by deconstructing prevalent prejudices about them and promoting empathic
      understanding. Mental health professionals may also advocate by providing
      information about social determinants refugee mental health to policy makers and
      promoting psychosocial interventions and protective social policies.

PMID- 29202663
TI  - Experiences of Patients with Mental Illness' Interactions with Medical Students:
      A Systematic Review.
AB  - OBJECTIVES: Mental health is a key area for learning within undergraduate medical
      education. Given the nature of mental illness, interactions may have the
      potential to uniquely affect patients. This study set out to systematically
      review studies reporting experiences and perceptions of patients with mental
      illness' clinical interactions with medical students. This includes which factors
      encourage patients to interact with medical students and if patients perceive
      negative and positive effects from these interactions. METHOD: Studies reporting
      patient experiences of involvement in undergraduate medicine were included. A
      standardised search of online databases was carried out independently by 2
      authors and consensus reached on the inclusion of studies. Data extraction and
      quality assessment were also completed independently, after which a content
      analysis of interventions was conducted and key themes extracted. Studies were
      included from peer-reviewed journals, in any language. RESULTS: Eight studies
      from 5 countries were included, totaling 1088 patients. Most patients regarded
      interacting with medical students as a positive experience. Patients described
      feeling comfortable with medical students, and the majority believed it is
      important for students to 'see real patients'. Patients described benefits to
      them as enjoyment, being involved in student education, and developing an illness
      narrative. CONCLUSIONS: Results suggest that most patients with mental illness
      want to interact with medical students, and this should be encouraged during
      student placements. Further research, however, is required to understand in more
      depth what else can be done to improve the comfort and willingness for patients
      to interact with students, including barriers to this.

PMID- 29202664
TI  - Suicide Attempts and Completions among Mothers Whose Children Were Taken into
      Care by Child Protection Services: A Cohort Study Using Linkable Administrative
      Data.
AB  - OBJECTIVE: The objective of this study is to examine suicide attempts and
      completions among mothers who had a child taken into care by child protection
      services (CPS). These mothers were compared with their biological sisters who did
      not have a child taken into care and with mothers who received services from CPS
      but did not have a child taken into care. METHODS: A retrospective cohort of
      mothers whose first child was born in Manitoba, Canada, between April 1, 1992,
      and March 31, 2015, is used. Rates among discordant biological sisters (1872
      families) were compared using fixed-effects Poisson regression models, and
      mothers involved with CPS (children in care [ n = 1872] and received services [ n
      = 9590]) were compared using a Poisson regression model. RESULTS: Compared with
      their biological sisters and mothers who received services, the adjusted
      incidence rate ratio (aIRR) of death by suicide was greater among mothers whose
      child was taken into care by CPS (aIRR = 4.46 [95% confidence interval (CI), 1.39
      14.33] and ARR = 3.45 [95% CI, 1.61-7.40], respectively). Incidence rates of
      suicide attempts were higher among mothers with a child taken into care compared
      with their sisters (aIRR = 2.15; 95% CI, 1.40-3.30) and mothers receiving
      services (aIRR = 2.82; 95% CI, 2.03-3.92). CONCLUSIONS: Mothers who had a child
      taken into care had significantly higher rates of suicide attempts and
      completions. When children are taken into care, physician and social workers
      should inquire about maternal suicidal behaviour and provide appropriate mental
      health.

PMID- 29202665
TI  - The Social Determinants of Refugee Mental Health in the Post-Migration Context: A
      Critical Review.
AB  - With the global increase in the number of refugees and asylum seekers, mental
      health professionals have become more aware of the need to understand and respond
      to the mental health needs of forced migrants. This critical review summarizes
      the findings of recent systematic reviews and primary research on the impact of
      post-migration conditions on mental disorders and PTSD among refugees and asylum
      seekers. Historically, the focus of mental health research and interventions with
      these populations has been on the impact of pre-migration trauma. Pre-migration
      trauma does predict mental disorders and PTSD, but the post-migration context can
      be an equally powerful determinant of mental health. Moreover, post-migration
      factors may moderate the ability of refugees to recover from pre-migration
      trauma. The importance of post-migration stressors to refugee mental health
      suggests the need for therapeutic interventions with psychosocial elements that
      address the broader conditions of refugee and asylum seekers' lives. However,
      there are few studies of multimodal interventions with refugees, and even fewer
      with control conditions that allow for conclusions about their effectiveness.
      These findings are interpreted using a social determinants of health framework
      that connects the risk and protective factors in the material and social
      conditions of refugees' post-migration lives to broader social, economic and
      political factors.

PMID- 29202666
TI  - DBCG hypo trial validation of radiotherapy parameters from a national data bank
      versus manual reporting.
AB  - INTRODUCTION: The current study evaluates the data quality achievable using a
      national data bank for reporting radiotherapy parameters relative to the
      classical manual reporting method of selected parameters. METHODS: The data
      comparison is based on 1522 Danish patients of the DBCG hypo trial with data
      stored in the Danish national radiotherapy data bank. In line with standard DBCG
      trial practice selected parameters were also reported manually to the DBCG
      database. Categorical variables are compared using contingency tables, and
      comparison of continuous parameters is presented in scatter plots. RESULTS: For
      categorical variables 25 differences between the data bank and manual values were
      located. Of these 23 were related to mistakes in the manual reported value whilst
      the remaining two were a wrong classification in the data bank. The wrong
      classification in the data bank was related to lack of dose information, since
      the two patients had been treated with an electron boost based on a manual
      calculation, thus data was not exported to the data bank, and this was not
      detected prior to comparison with the manual data. For a few database fields in
      the manual data an ambiguity of the parameter definition of the specific field is
      seen in the data. This was not the case for the data bank, which extract all data
      consistently. CONCLUSIONS: In terms of data quality the data bank is superior to
      manually reported values. However, there is a need to allocate resources for
      checking the validity of the available data as well as ensuring that all relevant
      data is present. The data bank contains more detailed information, and thus
      facilitates research related to the actual dose distribution in the patients.

PMID- 29202667
TI  - Percutaneous microwave ablation of renal cell carcinoma using a high power
      microwave system: focus upon safety and efficacy.
AB  - OBJECTIVES: Percutaneous ablation is an expanding, minimally invasive approach
      for small- to medium-sized renal masses. The purpose of this study is to review
      safety, and mid-term efficacy of percutaneous microwave ablation (MWA) for Renal
      Cell Carcinoma (RCC) treatment using a high power microwave system. METHODS AND
      MATERIALS: Institutional database research identified 50 consecutive patients
      with a single lesion resembling renal cell carcinoma in CT and MRI who underwent
      percutaneous microwave ablation using a high power microwave system. All patients
      underwent biopsy on the same session with ablation using an 18G semi-automatic
      soft tissue biopsy needle. Contrast-enhanced computed tomography or magnetic
      resonance imaging was used for post-ablation follow-up. Patient and tumour
      characteristics, microwave technique, complications and pattern of recurrence
      were evaluated. RESULTS: Mean patient age was 74 years (male-female: 31-19).
      Average lesion size was 3.1 cm (range 2.0-4.3 cm). Biopsy results report RCC (n =
      48), inflammatory myofibroblastic tumour (n = 1), and non-diagnostic sample (n =
      1). The 3-year overall survival was 95.8% (46/48). Two patients died during the 3
      year follow-up period due to causes unrelated to the MW ablation and to the RCC.
      Minor complications including haematomas requiring nothing but observation
      occurred at 4% (2/50) of the cases. Local recurrence of 6.25% (3/48) was observed
      with 2/3 cases being re-treated achieving a total clinical success of 97.9%
      (47/48 lesions). CONCLUSIONS: Percutaneous microwave ablation of RCC using a high
      power microwave system is a safe and efficacious technique for the treatment of
      small- to medium-sized renal masses.

PMID- 29202668
TI  - Quality of life and care needs in women with estrogen positive metastatic breast
      cancer: a qualitative study.
AB  - BACKGROUND: In recent years, the prognosis of metastatic breast cancer (MBC) has
      improved with more effective therapies applicable to a wider range of patients.
      To many patients, a MBC diagnosis thus initiates a prolonged course of illness
      and treatment. This qualitative study aimed to explore the long-term health
      related quality of life (HRQoL) and support needs in MBC patients of all ages in
      the Danish context. MATERIAL AND METHODS: Eighteen MBC patients participated in
      five qualitative focus group interviews that were analyzed using content analysis
      and a constructivist approach. RESULTS: The participants described how MBC
      severely reduced their physical and psychosocial functioning and required a
      constant adaptation of their quality of life (QoL) standards in relation to their
      changing life situation and disease progression. Overall, they felt medically
      well-treated but lacked a multidisciplinary approach to care including
      psychological support, in particular, but also manual physiotherapy, health care
      coordination and social counseling. The participants called for continuity of
      care with the same health care professionals as this facilitated communication
      and flexibility in planning treatment and controls. They requested a reduction of
      precious time spend on treatment to enable them to focus on their most meaningful
      relations and activities. CONCLUSION: With the MBC diagnosis, the focus of
      treatment switches from disease eradication to prolonging survival, alleviating
      symptoms and improving QoL. To patients, MBC marks a shift in expectations from
      quantity to quality of life and a perpetual adaptation of their QoL standards. To
      sustain patients' HRQoL, it is important that along with improvements in life
      prolonging treatment, comprehensive care also supports their main psycho-social
      needs. These patients needed support in maintaining normality and role
      functioning enabling them to focus on living, not merely surviving, through this
      prolonged disease phase.

PMID- 29202669
TI  - The relationship between smell identification and neuropsychological domains:
      Results from a sample of community-dwelling adults suspected of dementia.
AB  - OBJECTIVE: This study aimed to test the theoretical relationships between smell
      identification and cognitive tasks based on existing neuroimaging and anatomical
      findings. METHOD: Utilizing data collected from a memory assessment clinic,
      theory-derived mediation and moderation models were tested. The sample used in
      this study consisted of 103 (39 male, 64 female) individuals referred for memory
      assessments. The sample's mean education was 12.4 years (SD = 3.2), and the mean
      age of the sample was 77.2 years (SD = 6.3). RESULTS: The University of
      Pennsylvania Smell Identification Test (UPSIT) was a significant, partial
      mediator of the relationship between the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) Immediate and Delayed Memory indexes. Olfactory
      identification did not mediate list learning and retrieval; however, olfactory
      identification was a significant partial mediator of the relationship between
      story encoding and later memory retrieval of the story. Olfactory identification
      also fully mediated the relationship between a visuospatial construction task and
      its reconstruction from memory after a short delay. The relationship between
      processing speed and the olfactory identification was significantly mediated by
      semantic memory. Finally, the UPSIT moderated the relationship between a measure
      of premorbid ability, the Wechsler Test of Adult Reading, and current global
      cognitive functioning. CONCLUSIONS: Our results support theoretical relationships
      between olfaction and neuropsychological domains. Additionally, our results
      suggest that the UPSIT may serve as a proxy for cerebral integrity and is likely
      related to the duration of neurodegeneration.

PMID- 29202670
TI  - Cardiovascular safety of non-steroidal anti-inflammatory drugs revisited.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to treat
      inflammatory pain for decades. More recently, newer NSAIDs were developed to
      target the inducible isoform of cyclooxygenase (COX), COX-2, with the aim of
      reducing gastrointestinal toxicity. While the COX-2 selective inhibitors were
      effective in reducing pain and gastrointestinal harm, they soon were associated
      with an increased risk of adverse cardiovascular events. Initially, the view
      emerged that selective inhibition of COX-2, and sparing of COX-1, was responsible
      for the increased cardiovascular harm observed. However, as more data from
      different human populations has become available this view has begun to be
      challenged. This review examines the current understanding of the role of
      prostaglandins and COX-1 and COX-2, particularly in platelets, the vasculature,
      and the kidney together with an overview of the cardiovascular and renal safety
      of both traditional NSAIDs and COX-2 selective inhibitors. Available data from
      active comparator randomized controlled trials, including the data from the
      PRECISION trial investigating the long term cardiovascular safety of patients
      exclusively with elevated baseline cardiovascular risk, are presented. The data,
      when considered holistically, support the idea that all NSAIDs carry some level
      of cardiovascular risk, be they traditional NSAIDs or COX-2 selective agents.
      There is also some evidence of heterogeneity of effect with NSAIDs particularly
      in relation to effects on blood pressure, with no clear demarcation based on the
      degree of COX-2 selectivity.

PMID- 29202671
TI  - Natural lymphatic ("atypical") actinobacillosis in cattle caused by
      Actinobacillus lignieresii.
AB  - Bovine actinobacillosis is typically characterized by pyogranulomatous glossitis
      (wooden tongue). The involvement of other tissues, generally the skin or lymph
      nodes, has been regarded as atypical or cutaneous. We describe herein 2 outbreaks
      of actinobacillosis affecting primarily the lymph nodes of the head and neck. The
      disease affected 40 of 540 lactating cows in a dairy herd, and 5 of 335 two-y-old
      steers in a beef herd. Multiple or single, occasionally ulcerated nodules were
      observed in the region of the mandible, neck, and shoulder, including the
      parotid, submandibular, retropharyngeal, and prescapular lymph nodes. The
      histologic lesions were multifocal pyogranulomatous lymphadenitis, dermatitis,
      and cellulitis with Splendore-Hoeppli material. One steer had an exophytic
      pyogranuloma in the gingiva and another died because of ruminal tympany secondary
      to oropharyngeal and esophageal obstruction by a pyogranulomatous mass.
      Actinobacillus lignieresii was isolated from the lesions and identified by
      amplification, sequencing, and analysis of the 16S ribosomal (r)DNA gene. Seven
      of 8 cows recovered after treatment with sodium iodide. Lymphatic
      actinobacillosis is a frequent disease in Uruguay, southern Brazil, and
      Argentina. Morbidity is 1-50%; mortality is <1%. A. lignieresii apparently
      penetrates the intact oral and pharyngeal mucosa, infecting primarily the
      regional lymph nodes. Later, lesions may extend to the subcutaneous tissue and
      the skin, causing ulceration. Affected cattle with draining pyogranulomas
      contaminate the environment, favoring disease transmission, and should be treated
      with sodium iodide or antibiotics and isolated from the herd in order to control
      the disease.

PMID- 29202672
TI  - Sensitivity and specificity levels of two rapid assays for antibodies to
      Anaplasma spp. in dogs.
AB  - Canine anaplasmosis is a tick-borne disease of dogs that results following
      infection with Anaplasma phagocytophilum or Anaplasma platys. The SNAP 4Dx Plus
      test (IDEXX Laboratories) and the VetScan Canine Anaplasma Rapid test (Abaxis)
      are commercial in-house rapid tests for the detection of antibody to these 2
      antigenically related Anaplasma species. We evaluated 2 tests using serum and
      whole blood samples obtained from reference laboratories and veterinary
      hospitals. Samples were obtained from regions of the country known to be habitats
      of the primary tick vectors. The A. phagocytophilum sample set comprised 236 dog
      sera from the northeastern and midwestern United States; the A. platys sample set
      comprised 179 sera from dogs living in the southwestern United States. An
      indirect immunofluorescent antibody (IFA) test and an A. platys species-specific
      ELISA were used as reference assays for the A. phagocytophilum and A. platys
      samples, respectively. The SNAP test demonstrated significantly higher
      sensitivity (84.7% for A. phagocytophilum and 83.1% for A. platys), compared to
      the VetScan test (39.0% for A. phagocytophilum and 57.6% for A. platys). The
      specificity of the SNAP test (95.8% for A. phagocytophilum and 99.2% for A.
      platys) was significantly greater than the VetScan test (85.6% for A.
      phagocytophilum and 82.5% for A. platys). In a separate clinic study, conducted
      within an A. phagocytophilum-endemic state (Minnesota) using 154 whole blood
      samples from client-owned dogs, the VetScan test was negative for 22 of 39 SNAP
      and IFA seropositive samples.

PMID- 29202673
TI  - Enzootic calcinosis in horses grazing Solanum glaucophyllum in Argentina.
AB  - Solanum glaucophyllum, a toxic plant known for its calcinogenic effects, causes
      enzootic calcinosis in ruminant and monogastric animals. We describe an outbreak
      of enzootic calcinosis that occurred in a herd of 110 horses grazing pastureland
      heavily contaminated with S. glaucophyllum in Buenos Aires province, Argentina.
      Ten horses developed clinical signs, and 6 horses died. Clinical signs included
      abnormal gait (stiff-legged action, short strides), stiffness, thoracolumbar
      kyphosis, reluctance to move, wide stance, chronic weight loss, weakness,
      recumbency, and difficulty standing. Autopsy of 2 horses revealed severe
      mineralization of the aorta, pulmonary arteries, heart, and lungs, consistent
      with enzootic calcinosis. Although horses usually have very selective grazing
      behavior, under food restriction conditions, they can ingest the toxic plants and
      can develop the disease. Enzootic calcinosis should be considered as a
      differential diagnosis in horses grazing S. glaucophyllum-invaded pasturelands
      with compatible clinical signs and lesions.

PMID- 29202674
TI  - Determination of the diversity of astroviruses in feces from cats in Florida.
AB  - Astroviruses are small, nonenveloped RNA viruses that have been linked to
      numerous diseases in a variety of species, including enteric disease in humans
      and cheetahs. Species Mamastrovirus 2, previously known as feline astrovirus, has
      been isolated from the feces of domestic cats and cheetahs. A total of 122 cat
      fecal samples from Alachua County, FL Animal Services and the Veterinary
      Community Outreach Program at the University of Florida were analyzed, and 35
      contained astroviral RNA that was amplified and identified using consensus RT-PCR
      and sequence analysis. Using phylogenetic analysis, 19 of the astroviral
      sequences were identified as Mamastrovirus 2, making it the most prevalent
      astrovirus in this population. Three samples were identified as an astrovirus
      similar to viruses previously identified in foxes in The Netherlands and a cat in
      California, and one was similar to a bat astrovirus. One astroviral sequence was
      identified as an Avastrovirus. Although a causative relationship between
      mamastroviruses and enteric disease in cats has yet to be established, it is
      clear that mamastroviruses are prevalent, and an understanding of prevalence of
      astroviral types may help direct future test development.

PMID- 29202676
TI  - Precision medicine for HIV: where are we?
AB  - To date, antiretroviral therapy is highly effective in HIV-affected patients, but
      the individualization of such a life-long therapy may be advised. This review
      briefly summarizes the main factors involved in the potential personalization of
      antiretroviral treatment. Relevant articles in English were identified by PubMed
      and recent congresses' abstracts. Foremost influences concerning
      pharmacodynamics, therapeutic drug monitoring, pharmacogenetics, comorbidities,
      immune recovery and viral characteristics affecting the healthcare of HIV
      positive patients are listed here. Furthermore, pharmacoeconomic aspects are
      mentioned. Applying pharmacokinetic and pharmacogenetic knowledge may be
      informative and guide the better choice of treatment in order to achieve long
      term efficacy and avoid adverse events. Randomized investigations of the clinical
      relevance of tailored antiretroviral regimens are needed in order to obtain a
      better management of HIV/AIDS-affected patients.

PMID- 29202675
TI  - Acute hepatic steatosis: a helpful diagnostic feature in metallic phosphide
      poisoned horses.
AB  - Metal phosphides, particularly zinc and aluminum phosphide, occasionally poison
      horses and other equids following their use as rodenticides and insecticides.
      Grain-based aluminum phosphide baits are used to control rodents such as prairie
      dogs. The clinical course in intoxicated horses is short (<24-48 h), and animals
      may be found dead. Hepatic lesions caused by phosphine poisoning are not well
      described. Laboratory confirmation depends on detecting phosphine gas in gastric
      contents. Eight horses and a mule were exposed to zinc phosphide used to control
      prairie dogs on a Wyoming ranch. Three of 9 exposed equids developed some
      combination of sweating, ataxia, anxiety, and colic; 2 died acutely, and 1
      recovered. A diagnosis of zinc phosphide was made by detecting phosphine in
      stomach contents from a horse and a mule. The liver was pale and swollen in the
      affected horse, which died after a clinical course of ~12 h. Other changes were
      generalized congestion and edema, pulmonary edema, and acute cerebrocortical
      edema. There was diffuse hepatocellular microvesicular steatosis. Similar
      histologic lesions were present in 7 equine livers from 2 previously published
      episodes of metallic phosphide poisoning. Older lesions (>24 h of clinical signs)
      had centrilobular hepatic necrosis with congestion and a mixture of
      microvesicular and macrovesicular steatosis. Phosphine poisoning should be
      considered in horses that die acutely and are found to have steatosis, either
      with or without hepatocellular necrosis.

PMID- 29202677
TI  - Cronkhite-Canada syndrome causing pouch outlet obstruction 5 years after roux-en
      y gastric bypass.
AB  - OBJECTIVE: We present the case of a 57-year-old man with a history of Roux-en-Y
      gastric bypass (RYGB) and colonic polyps who presented with an upper
      gastrointestinal obstruction based on massive stomach polyposis in the pouch.
      METHODS: Two months prior to this acute admission, he had undergone resection of
      the gastric remnant due to massive refractory intraluminal bleeding from a
      polypoid mass. Ten years earlier, right colectomy was performed due to
      hypertrophic polyposis unsuitable for endoscopic polypectomy. Upper
      gastrointestinal endoscopy showed a polypoid mass in the pouch causing
      obstruction. Benign biopsies were obtained. A resection of the stomach pouch with
      esophagojejunostomy was performed. Macroscopic evaluation of the pouch lumen
      showed massive polyposis with a sharp demarcation near the Z-line and at the
      gastrojejunostomy. On clinical examination, the presence of atrophic nail
      changes, alopecia, and palmar hyperpigmentation was noticed. RESULTS:
      Postoperative course was uneventful and feeding was restarted successfully.
      Histological analysis revealed hyperplastic polypoid tissue, which resembled the
      polyps in the stomach remnant and colon. Together with the ectodermal changes,
      the diagnose of Cronkhite-Canada syndrome was established. CONCLUSION: Diffuse
      polyposis in Cronkhite-Canada syndrome is a rare cause for pouch obstruction
      after RYGB. Clinical examination should focus on dermatologic findings.

PMID- 29202679
TI  - CME Opportunities and Save the Date.

PMID- 29202681
TI  - Medicare, Value-Based Purchasing, and the Law of Unintended Consequences.

PMID- 29202678
TI  - Approach to thrombosis at unusual sites: Splanchnic and cerebral vein thrombosis.
AB  - Splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) are two
      manifestations of unusual site venous thromboembolism (VTE). SVT includes
      thrombosis in the portal, mesenteric or splenic veins, and the Budd-Chiari
      syndrome. CVT encompasses thrombosis of the dural venous sinuses and thrombosis
      of the cerebral veins. Unusual site VTE often represents a diagnostic and
      therapeutic challenge because of the heterogeneity in clinical presentation, the
      limited evidence available in the literature on the acute and long-term prognosis
      of these diseases, and the lack of large randomized controlled trials evaluating
      different treatment options. This narrative review describes the approach to
      patients with SVT or CVT by examining the diagnostic process, the assessment of
      potential risk factors and the appropriate anticoagulant treatment.

PMID- 29202682
TI  - Severe Vitamin D Deficiency at Admission and Shock Reversal.

PMID- 29202683
TI  - Successful use of snare electrocautery via flexible fiberoptic bronchoscopy for
      removal of an endobronchial hamartoma causing chronic lung atelectasis and
      mimicking malignancy.
AB  - We present a rare case of giant endobronchial hamartoma coexisting with lung
      atelectasis for more than 3 years. The small specimen initially biopsied via
      bronchoscope did not reveal tissue features, but some features were suspicious
      for squamous cell carcinoma. The lesion was removed completely using snare
      electrocautery combined with argon plasma coagulation via flexible fiberoptic
      bronchoscopy. The patient made a satisfactory recovery, and a pathological
      diagnosis was made. This could be a useful option in selected endobronchial
      tumors.

PMID- 29202684
TI  - Voluntary cough intensity and its influencing factors differ by sex in community
      dwelling adults.
AB  - BACKGROUND: Cough peak flow (CPF) is widely used for measuring voluntary cough
      intensity. However, the respective factors that affect CPF are not known. The aim
      of this study was to determine the factors affecting CPF by sex in community
      dwelling adults. METHOD: We recruited participants using posters exhibited at a
      public gymnasium. Participation was voluntary, and all participants provided
      informed consent. Nonsmoking community residents (102 males, 49.6 +/- 20.2 years
      of age; 101 females, 51.4 +/- 18.4 years of age) participated in this study. The
      main outcome measures were sex differences in CPF, respiratory function,
      respiratory muscle strength, thorax extension, and grip strength. Factors
      affecting CPF by sex were analyzed using multiple regression analysis. RESULTS:
      All parameters were higher in men than in women. CPF was affected by thorax
      expansion at the tenth rib, inspiratory muscle strength and forced expiration in
      1 s in men, and thorax expansion at the tenth rib, inspiratory reserve volume,
      and expiratory muscle power in women. A weak negative correlation was observed
      between CPF and age ( p = -0.24, p < 0.05) in women. CONCLUSIONS: The factors
      affecting CPF differed by sex in community-dwelling adults. Clinical Trial
      Number: UMIN000023912.

PMID- 29202685
TI  - Accuracies of univariate and multivariate genomic prediction models in African
      cassava.
AB  - BACKGROUND: Genomic selection (GS) promises to accelerate genetic gain in plant
      breeding programs especially for crop species such as cassava that have long
      breeding cycles. Practically, to implement GS in cassava breeding, it is
      necessary to evaluate different GS models and to develop suitable models for an
      optimized breeding pipeline. In this paper, we compared (1) prediction accuracies
      from a single-trait (uT) and a multi-trait (MT) mixed model for a single
      environment genetic evaluation (Scenario 1), and (2) accuracies from a compound
      symmetric multi-environment model (uE) parameterized as a univariate multi-kernel
      model to a multivariate (ME) multi-environment mixed model that accounts for
      genotype-by-environment interaction for multi-environment genetic evaluation
      (Scenario 2). For these analyses, we used 16 years of public cassava breeding
      data for six target cassava traits and a fivefold cross-validation scheme with 10
      repeat cycles to assess model prediction accuracies. RESULTS: In Scenario 1, the
      MT models had higher prediction accuracies than the uT models for all traits and
      locations analyzed, which amounted to on average a 40% improved prediction
      accuracy. For Scenario 2, we observed that the ME model had on average (across
      all locations and traits) a 12% improved prediction accuracy compared to the uE
      model. CONCLUSIONS: We recommend the use of multivariate mixed models (MT and ME)
      for cassava genetic evaluation. These models may be useful for other plant
      species.

PMID- 29202686
TI  - Species-specific genes under selection characterize the co-evolution of
      slavemaker and host lifestyles.
AB  - BACKGROUND: The transition to a parasitic lifestyle entails comprehensive changes
      to the selective regime. In parasites, genes encoding for traits that facilitate
      host detection, exploitation and transmission should be under selection.
      Slavemaking ants are social parasites that exploit the altruistic behaviour of
      their hosts by stealing heterospecific host brood during raids, which afterwards
      serve as slaves in slavemaker nests. Here we search for evidence of selection in
      the transcriptomes of three slavemaker species and three closely related hosts.
      We expected selection on genes underlying recognition and raiding or defense
      behaviour. Analyses of selective forces in species with a slavemaker or host
      lifestyle allowed investigation into whether or not repeated instances of
      slavemaker evolution share the same genetic basis. To investigate the genetic
      basis of host-slavemaker co-evolution, we created orthologous clusters from
      transcriptome sequences of six Temnothorax ant species - three slavemakers and
      three hosts - to identify genes with signatures of selection. We further tested
      for functional enrichment in selected genes from slavemakers and hosts
      respectively and investigated which pathways the according genes belong to.
      RESULTS: Our phylogenetic analysis, based on more than 5000 ortholog sequences,
      revealed sister species status for two slavemakers as well as two hosts,
      contradicting a previous phylogeny based on mtDNA. We identified 309 genes with
      signs of positive selection on branches leading to slavemakers and 161 leading to
      hosts. Among these were genes potentially involved in cuticular hydrocarbon
      synthesis, thus species recognition, and circadian clock functionality possibly
      explaining the different activity patterns of slavemakers and hosts. There was
      little overlap of genes with signatures of positive selection among species,
      which are involved in numerous different functions and different pathways.
      CONCLUSIONS: We identified different genes, functions and pathways under positive
      selection in each species. These results point to species-specific adaptations
      rather than convergent trajectories during the evolution of the slavemaker and
      host lifestyles suggesting that the evolution of parasitism, even in closely
      related species, may be achieved in diverse ways.

PMID- 29202687
TI  - Total evidence phylogeny and evolutionary timescale for Australian faunivorous
      marsupials (Dasyuromorphia).
AB  - BACKGROUND: The order Dasyuromorphia is a diverse radiation of faunivorous
      marsupials, comprising >80 modern species in Australia and New Guinea. It
      includes dasyurids, the numbat (the myrmecobiid Myrmecobius fasciatus) and the
      recently extinct thylacine (the thylacinid Thylacinus cyncocephalus). There is
      also a diverse fossil record of dasyuromorphians and "dasyuromorphian-like" taxa
      known from Australia. We present the first total evidence phylogenetic analyses
      of the order, based on combined morphological and molecular data (including a
      novel set of 115 postcranial characters), to resolve relationships and calculate
      divergence dates. We use this information to analyse the diversification dynamics
      of modern dasyuromorphians. RESULTS: Our morphology-only analyses are poorly
      resolved, but our molecular and total evidence analyses confidently resolve most
      relationships within the order, and are strongly congruent with recent molecular
      studies. Thylacinidae is the first family to diverge within the order, and there
      is strong support for four tribes within Dasyuridae (Dasyurini, Phascogalini,
      Planigalini and Sminthopsini). Among fossil taxa, Ankotarinja and Keeuna do not
      appear to be members of Dasyuromorphia, whilst Barinya and Mutpuracinus are of
      uncertain relationships within the order. Divergence dates calculated using total
      evidence tip-and-node dating are younger than both molecular node-dating and
      total evidence tip-dating, but appear more congruent with the fossil record and
      are relatively insensitive to calibration strategy. The tip-and-node divergence
      dates indicate that Dasyurini, Phascogalini and Sminthopsini began to radiate
      almost simultaneously during the middle-to-late Miocene (11.5-13.1 MYA; composite
      95% HPD: 9.5-15.9 MYA); the median estimates for these divergences are shortly
      after a drop in global temperatures (the middle Miocene Climatic Transition), and
      coincide with a faunal turnover event in the mammalian fossil record of
      Australia. Planigalini radiated much later, during the latest Miocene to earliest
      Pliocene (6.5 MYA; composite 95% HPD: 4.4-8.9 MYA); the median estimates for
      these divergences coincide with an increase in grass pollen in the Australian
      palynological record that suggests the development of more open habitats, which
      are preferred by modern planigale species. CONCLUSIONS: Our results provide a
      phylogenetic and temporal framework for interpreting the evolution of modern and
      fossil dasyuromorphians, but future progress will require a much improved fossil
      record.

PMID- 29202688
TI  - Rethinking the evolution of eukaryotic metabolism: novel cellular partitioning of
      enzymes in stramenopiles links serine biosynthesis to glycolysis in mitochondria.
AB  - BACKGROUND: An important feature of eukaryotic evolution is metabolic
      compartmentalization, in which certain pathways are restricted to the cytosol or
      specific organelles. Glycolysis in eukaryotes is described as a cytosolic
      process. The universality of this canon has been challenged by recent genome data
      that suggest that some glycolytic enzymes made by stramenopiles bear
      mitochondrial targeting peptides. RESULTS: Mining of oomycete, diatom, and brown
      algal genomes indicates that stramenopiles encode two forms of enzymes for the
      second half of glycolysis, one with and the other without mitochondrial targeting
      peptides. The predicted mitochondrial targeting was confirmed by using
      fluorescent tags to localize phosphoglycerate kinase, phosphoglycerate mutase,
      and pyruvate kinase in Phytophthora infestans, the oomycete that causes potato
      blight. A genome-wide search for other enzymes with atypical mitochondrial
      locations identified phosphoglycerate dehydrogenase, phosphoserine
      aminotransferase, and phosphoserine phosphatase, which form a pathway for
      generating serine from the glycolytic intermediate 3-phosphoglycerate.
      Fluorescent tags confirmed the delivery of these serine biosynthetic enzymes to
      P. infestans mitochondria. A cytosolic form of this serine biosynthetic pathway,
      which occurs in most eukaryotes, is missing from oomycetes and most other
      stramenopiles. The glycolysis and serine metabolism pathways of oomycetes appear
      to be mosaics of enzymes with different ancestries. While some of the
      noncanonical oomycete mitochondrial enzymes have the closest affinity in
      phylogenetic analyses with proteins from other stramenopiles, others cluster with
      bacterial, plant, or animal proteins. The genes encoding the mitochondrial
      phosphoglycerate kinase and serine-forming enzymes are physically linked on
      oomycete chromosomes, which suggests a shared origin. CONCLUSIONS: Stramenopile
      metabolism appears to have been shaped through the acquisition of genes by
      descent and lateral or endosymbiotic gene transfer, along with the targeting of
      the proteins to locations that are novel compared to other eukaryotes.
      Colocalization of the glycolytic and serine biosynthesis enzymes in mitochondria
      is apparently necessary since they share a common intermediate. The results
      indicate that descriptions of metabolism in textbooks do not cover the full
      diversity of eukaryotic biology.

PMID- 29202689
TI  - Explorative visual analytics on interval-based genomic data and their metadata.
AB  - BACKGROUND: With the wide-spreading of public repositories of NGS processed data,
      the availability of user-friendly and effective tools for data exploration,
      analysis and visualization is becoming very relevant. These tools enable
      interactive analytics, an exploratory approach for the seamless "sense-making" of
      data through on-the-fly integration of analysis and visualization phases,
      suggested not only for evaluating processing results, but also for designing and
      adapting NGS data analysis pipelines. RESULTS: This paper presents abstractions
      for supporting the early analysis of NGS processed data and their implementation
      in an associated tool, named GenoMetric Space Explorer (GeMSE). This tool serves
      the needs of the GenoMetric Query Language, an innovative cloud-based system for
      computing complex queries over heterogeneous processed data. It can also be used
      starting from any text files in standard BED, BroadPeak, NarrowPeak, GTF, or
      general tab-delimited format, containing numerical features of genomic regions;
      metadata can be provided as text files in tab-delimited attribute-value format.
      GeMSE allows interactive analytics, consisting of on-the-fly cycling among steps
      of data exploration, analysis and visualization that help biologists and
      bioinformaticians in making sense of heterogeneous genomic datasets. By means of
      an explorative interaction support, users can trace past activities and quickly
      recover their results, seamlessly going backward and forward in the analysis
      steps and comparative visualizations of heatmaps. CONCLUSIONS: GeMSE effective
      application and practical usefulness is demonstrated through significant use
      cases of biological interest. GeMSE is available at
      http://www.bioinformatics.deib.polimi.it/GeMSE/ , and its source code is
      available at https://github.com/Genometric/GeMSE under GPLv3 open-source license.

PMID- 29202690
TI  - Distinct patterns of serum hepatitis B core-related antigen during the natural
      history of chronic hepatitis B.
AB  - BACKGROUND: The current clinical practice on chronic hepatitis B (CHB) requires
      better on-treatment monitoring of viral persistence. Quantified assays for
      hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold
      promise for further optimization of therapy. Here, we aimed to characterize
      HBcrAg during the natural course of CHB. METHODS: Four-hundred and forty four
      treatment naive CHB patients, who all underwent liver histology examination, were
      enrolled in this cross-sectional study. Their HBV DNA, HBsAg, HBeAg and HBcrAg
      titres were quantified and analyzed in the context of four distinct clinical
      phases. Correlation of HBcrAg and HBsAg with other markers were performed. The
      relationship between liver and serum antigen levels were also assessed. RESULTS:
      HBcrAg, like HBsAg, exhibited high degree of correlation with HBV DNA. However, a
      more significant linear relationship was found between HBcrAg and HBeAg titre in
      immune tolerant (IT) and immune clearance (IC) phases, while in HBeAg negative
      hepatitis (ENH) group, HBV DNA is a major determinant of HBcrAg. Significant
      difference was observed in liver HBcAg score and HBcrAg level in both IT and IC
      phases whereas barely significant positive correlations between liver HBsAg score
      and HBsAg titre was documented. CONCLUSION: HBcrAg titre exhibited distinct
      correlative profile in a phase-specific manner. In addition, its level is well
      related to the intrahepatic expression of core antigen. It has a considerable
      utility in monitoring and refining antiviral therapy.

PMID- 29202691
TI  - Performance of the marginal structural cox model for estimating individual and
      joined effects of treatments given in combination.
AB  - BACKGROUND: The Marginal Structural Cox Model (Cox-MSM), an alternative approach
      to handle time-dependent confounder, was introduced for survival analysis and
      applied to estimate the joint causal effect of two time-dependent nonrandomized
      treatments on survival among HIV-positive subjects. Nevertheless, Cox-MSM
      performance in the case of multiple treatments has not been fully explored under
      different degree of time-dependent confounding for treatments or in case of
      interaction between treatments. We aimed to evaluate and compare the performance
      of the marginal structural Cox model (Cox-MSM) to the standard Cox model in
      estimating the treatment effect in the case of multiple treatments under
      different scenarios of time-dependent confounding and when an interaction between
      treatment effects is present. METHODS: We specified a Cox-MSM with two treatments
      including an interaction term for situations where an adverse event might be
      caused by two treatments taken simultaneously but not by each treatment taken
      alone. We simulated longitudinal data with two treatments and a time-dependent
      confounder affected by one or the two treatments. To fit the Cox-MSM, we used the
      inverse probability weighting method. We illustrated the method to evaluate the
      specific effect of protease inhibitors combined (or not) to other antiretroviral
      medications on the anal cancer risk in HIV-infected individuals, with CD4 cell
      count as time-dependent confounder. RESULTS: Overall, Cox-MSM performed better
      than the standard Cox model. Furthermore, we showed that estimates were unbiased
      when an interaction term was included in the model. CONCLUSION: Cox-MSM may be
      used for accurately estimating causal individual and joined treatment effects
      from a combination therapy in presence of time-dependent confounding provided
      that an interaction term is estimated.

PMID- 29202692
TI  - A comparative analysis of nonhost resistance across the two Triticeae crop
      species wheat and barley.
AB  - BACKGROUND: Nonhost resistance (NHR) protects plants against a vast number of non
      adapted pathogens which implicates a potential exploitation as source for novel
      disease resistance strategies. Aiming at a fundamental understanding of NHR a
      global analysis of transcriptome reprogramming in the economically important
      Triticeae cereals wheat and barley, comparing host and nonhost interactions in
      three major fungal pathosystems responsible for powdery mildew (Blumeria graminis
      ff. ssp.), cereal blast (Magnaporthe sp.) and leaf rust (Puccinia sp.) diseases,
      was performed. RESULTS: In each pathosystem a significant transcriptome
      reprogramming by adapted- or non-adapted pathogen isolates was observed, with
      considerable overlap between Blumeria, Magnaporthe and Puccinia. Small subsets of
      these general pathogen-regulated genes were identified as differentially
      regulated between host and corresponding nonhost interactions, indicating a fine
      tuning of the general pathogen response during the course of co-evolution.
      Additionally, the host- or nonhost-related responses were rather specific for
      each pair of adapted and non-adapted isolates, indicating that the nonhost
      resistance-related responses were to a great extent pathosystem-specific. This
      pathosystem-specific reprogramming may reflect different resistance mechanisms
      operating against non-adapted pathogens with different lifestyles, or equally,
      different co-option of the hosts by the adapted isolates to create an optimal
      environment for infection. To compare the transcriptional reprogramming between
      wheat and barley, putative orthologues were identified. Within the wheat and
      barley general pathogen-regulated genes, temporal expression profiles of
      orthologues looked similar, indicating conserved general responses in Triticeae
      against fungal attack. However, the comparison of orthologues differentially
      expressed between host and nonhost interactions revealed fewer commonalities
      between wheat and barley, but rather suggested different host or nonhost
      responses in the two cereal species. CONCLUSIONS: Taken together, our results
      suggest independent co-evolutionary forces acting on host pathosystems mirrored
      by barley- or wheat-specific nonhost responses. As a result of evolutionary
      processes, at least for the pathosystems investigated, NHR appears to rely on
      rather specific plant responses.

PMID- 29202693
TI  - Functional analysis of the GRMZM2G174449 promoter to identify Rhizoctonia solani
      inducible cis-elements in maize.
AB  - BACKGROUND: Banded leaf and sheath blight (BLSB), caused by the necrotrophic
      fungus Rhizoctonia solani, is a highly devastating disease in most maize and rice
      growing areas of the world. However, the molecular mechanisms of perceiving
      pathogen signals are poorly understood in hosts. RESULTS: Here, we identified a
      Rhizoctonia solani-inducible promoter pGRMZM2G174449 in maize. Deletion analysis
      showed that the -574 to -455 fragment was necessary for pGRMZM2G174449 in
      responding to R. solani and this fragment contained the unknown pathogen
      inducible cis-elements according to the bioinformatics analysis. Furthermore,
      detailed quantitative assays showed that two cis-elements, GCTGA in the -567 to 
      563 region and TATAT in the -485 to -481 region, were specifically responsible
      for the R. solani-inducible activity. A series of point mutation analysis
      indicated that the two cis-elements have the conserved motifs of NHWGN and DWYWT,
      respectively. CONCLUSION: Our results indicated that pGRMZM2G174449 is a good R.
      solani-inducible promoter suitable for genetic engineering of BLSB resistance.
      And NHWGN and DWYWT are two R. solani-inducible cis-elements that play important
      roles in pGRMZM2G174449 responding to R. solani.

PMID- 29202694
TI  - Alternative patterns of sex chromosome differentiation in Aedes aegypti (L).
AB  - BACKGROUND: Some populations of West African Aedes aegypti, the dengue and zika
      vector, are reproductively incompatible; our earlier study showed that divergence
      and rearrangements of genes on chromosome 1, which bears the sex locus (M), may
      be involved. We also previously described a proposed cryptic subspecies SenAae
      (PK10, Senegal) that had many more high inter-sex FST genes on chromosome 1 than
      did Ae.aegypti aegypti (Aaa, Pai Lom, Thailand). The current work more thoroughly
      explores the significance of those findings. RESULTS: Intersex standardized
      variance (FST) of single nucleotide polymorphisms (SNPs) was characterized from
      genomic exome capture libraries of both sexes in representative natural
      populations of Aaa and SenAae. Our goal was to identify SNPs that varied in
      frequency between males and females, and most were expected to occur on
      chromosome 1. Use of the assembled AaegL4 reference alleviated the previous
      problem of unmapped genes. Because the M locus gene nix was not captured and not
      present in AaegL4, the male-determining locus, per se, was not explored. Sex
      associated genes were those with FST values >= 0.100 and/or with increased
      expected heterozygosity (H exp , one-sided T-test, p < 0.05) in males. There were
      85 genes common to both collections with high inter-sex FST values; all genes but
      one were located on chromosome 1. Aaa showed the expected cluster of high inter
      sex FST genes proximal to the M locus, whereas SenAae had inter-sex FST genes
      along the length of chromosome 1. In addition, the Aaa M-locus proximal region
      showed increased H exp levels in males, whereas SenAae did not. In SenAae,
      chromosomal rearrangements and subsequent suppressed recombination may have
      accelerated X-Y differentiation. CONCLUSIONS: The evidence presented here is
      consistent with differential evolution of proto-Y chromosomes in Aaa and SenAae.

PMID- 29202696
TI  - ROSC rates and live discharge rates after cardiopulmonary resuscitation by
      different CPR teams - a retrospective cohort study.
AB  - BACKGROUND: Previous studies have reported that the quality of cardiopulmonary
      resuscitation (CPR) is closely associated with patient outcomes. The aim of this
      study was to compare patient CPR outcomes across resident, emergency medicine,
      and rapid response teams. METHODS: The records of patients who underwent CPR at
      the Seoul National University Bundang Hospital from January 1, 2013 to December
      31, 2016 were analyzed retrospectively. Return of spontaneous circulation, 10-
      and 30-day survival, and live discharge after return of spontaneous circulation
      were compared across patients treated by the three CPR teams. RESULTS: Of the
      1145 CPR cases, 444 (39%) were conducted by the resident team, 431 (38%) by the
      rapid response team, and 270 (23%) by the emergency medicine team. The adjusted
      odds ratios for the return of spontaneous circulation and subsequent 10-day
      survival among patients who received CPR from the resident team compared to the
      rapid response team were 0.59 (P = 0.001) and 0.71 (P = 0.037), respectively.
      There were no significant differences in the 30-day survival and rate of live
      discharge between patients who received CPR from the rapid response and resident
      teams; likewise, no significant differences were observed between patients who
      received CPR from the emergency medicine and rapid response teams. CONCLUSIONS:
      Patients receiving CPR from the rapid response team may have higher 10-day
      survival and return of spontaneous circulation rates than those who receive CPR
      from the resident team. However, our results are limited by the differences in
      approach, time of CPR, and room settings between teams.

PMID- 29202695
TI  - Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver
      development.
AB  - BACKGROUND: The differentiation and maturation trajectories of fetal liver
      stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution,
      and a priori knowledge of limited biomarkers could restrict trajectory tracking.
      RESULTS: We employed marker-free single-cell RNA-Seq to characterize
      comprehensive transcriptional profiles of 507 cells randomly selected from seven
      stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver
      development, and also 52 Epcam-positive cholangiocytes from postnatal day 3.25
      mouse livers. LSPCs in developing mouse livers were identified via marker-free
      transcriptomic profiling. Single-cell resolution dynamic developmental
      trajectories of LSPCs exhibited contiguous but discrete genetic control through
      transcription factors and signaling pathways. The gene expression profiles of
      cholangiocytes were more close to that of embryonic day 11.5 rather than other
      later staged LSPCs, cuing the fate decision stage of LSPCs. Our marker-free
      approach also allows systematic assessment and prediction of isolation biomarkers
      for LSPCs. CONCLUSIONS: Our data provide not only a valuable resource but also
      novel insights into the fate decision and transcriptional control of self
      renewal, differentiation and maturation of LSPCs.

PMID- 29202697
TI  - Genetic diversity and association mapping of mineral element concentrations in
      spinach leaves.
AB  - BACKGROUND: Spinach is a useful source of dietary vitamins and mineral elements.
      Breeding new spinach cultivars with high nutritional value is one of the main
      goals in spinach breeding programs worldwide, and identification of single
      nucleotide polymorphism (SNP) markers for mineral element concentrations is
      necessary to support spinach molecular breeding. The purpose of this study was to
      conduct a genome-wide association study (GWAS) and to identify SNP markers
      associated with mineral elements in the USDA-GRIN spinach germplasm collection.
      RESULTS: A total of 14 mineral elements: boron (B), calcium (Ca), cobalt (Co),
      copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), molybdenum
      (Mo), sodium (Na), nickel (Ni), phosphorus (P), sulfur (S), and zinc (Zn) were
      evaluated in 292 spinach accessions originally collected from 29 countries.
      Significant genetic variations were found among the tested genotypes as evidenced
      by the 2 to 42 times difference in mineral concentrations. A total of 2402 SNPs
      identified from genotyping by sequencing (GBS) approach were used for genetic
      diversity and GWAS. Six statistical methods were used for association analysis.
      Forty-five SNP markers were identified to be strongly associated with the
      concentrations of 13 mineral elements. Only two weakly associated SNP markers
      were associated with K concentration. Co-localized SNPs for different elemental
      concentrations were discovered in this research. Three SNP markers,
      AYZV02017731_40, AYZV02094133_57, and AYZV02281036_185 were identified to be
      associated with concentrations of four mineral components, Co, Mn, S, and Zn.
      There is a high validating correlation coefficient with r > 0.7 among
      concentrations of the four elements. Thirty-one spinach accessions, which rank in
      the top three highest concentrations in each of the 14 mineral elements, were
      identified as potential parents for spinach breeding programs in the future.
      CONCLUSIONS: The 45 SNP markers strongly associated with the concentrations of
      the 13 mineral elements: B, Ca, Co, Cu, Fe, Mg, Mn, Mo, Na, Ni, P, S, and Zn
      could be used in breeding programs to improve the nutritional quality of spinach
      through marker-assisted selection (MAS). The 31 spinach accessions with high
      concentrations of one to several mineral elements can be used as potential
      parents for spinach breeding programs.

PMID- 29202698
TI  - Safety and applicability of a pre-stage public access ventilator for trained
      laypersons: a proof of principle study.
AB  - BACKGROUND: Contemporary resuscitation guidelines for basic life support
      recommend an immediate onset of cardiac compressions in case of cardiac arrest
      followed by rescue breaths. Effective ventilation is often omitted due to fear of
      doing harm and fear of infectious diseases. In order to improve ventilation a pre
      stage of an automatic respirator was developed for use by laypersons. METHODS:
      Fifty-two healthy volunteers were ventilated by means of a prototype respirator
      via a full-face mask in a pilot study. The pre-stage public access ventilator
      (PAV) consisted of a low-cost self-designed turbine, with sensors for
      differential pressure, flow, FO2, FCO2 and 3-axis acceleration measurement.
      Sensor outputs were used to control the respirator and to recognize conditions
      relevant for efficiency of ventilation and patients' safety. Different
      respiratory manoeuvres were applied: a) pressure controlled ventilation (PCV), b)
      PCV with controlled leakage and c) PCV with simulated airway occlusion. Sensor
      signals were analysed to detect leakage and airway occlusion. Detection based
      upon sensor signals was compared with evaluation based on clinical observation
      and additional parameters such as exhaled CO2. RESULTS: Pressure controlled
      ventilation could be realized in all volunteers. Leakage was recognized with
      93.5% sensitivity and 93.5% specificity. Simulated airway occlusion was detected
      with 91.8% sensitivity and 91.7% specificity. CONCLUSION: The pre-stage PAV was
      able to detect potential complications relevant for patients' safety such as
      leakage and airway occlusion in a proof of principle study. Prospectively, this
      device provides a respectable basis for the development of an automatic emergency
      respirator and may help to improve bystander resuscitation.

PMID- 29202699
TI  - Comparison of lipopolysaccharides composition of two different strains of
      Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic
      bacterium that is recognized as a major cause of chronic gastritis, peptic
      ulcers, and gastric cancer. Comparable to other Gram-negative bacteria,
      lipopolysaccharides (LPS) are an important cellular component of the outer
      membrane of H. pylori. The LPS of this organism plays a key role in its
      colonization and persistence in the stomach. In addition, H. pylori LPS modulates
      pathogen-induced host inflammatory responses resulting in chronic inflammation
      within the gastrointestinal tract. Very little is known about the comparative LPS
      compositions of different strains of H. pylori with varied degree of virulence in
      human. Therefore, LPS was analyzed from two strains of H. pylori with differing
      potency in inducing inflammatory responses (SS1 and G27). LPS were extracted from
      aqueous and phenol layer of hot-phenol water extraction method and subjected for
      composition analysis by gas chromatography - mass spectrometry (GC-MS) to sugar
      and fatty acid compositions. RESULTS: The major difference between the two
      strains of H. pylori is the presence of Rhamnose, Fucose and GalNAc in the SS1
      strain, which was either not found or with low abundance in the G27 strain. On
      the other hand, high amount of Mannose was present in G27 in comparison to SS1.
      Fatty acid composition of lipid-A portion also showed considerable amount of
      differences between the two strains, phenol layer of SS1 had enhanced amount of 3
      hydroxy decanoic acid (3-OH-C10:0) and 3-hydroxy dodecanoic acid (3-OH-C12:0)
      which were not present in G27, whereas myristic acid (C14:0) was present in G27
      in relatively high amount. CONCLUSION: The composition analysis of H. pylori LPS,
      revealed differences in sugars and fatty acids composition between a mouse
      adapted strain SS1 and G27. This knowledge provides a novel way to dissect out
      their importance in host-pathogen interaction in further studies.

PMID- 29202700
TI  - Characterization of lpaH2 gene corresponding to lipopeptide synthesis in Bacillus
      amyloliquefaciens HAB-2.
AB  - BACKGROUND: Bacillus spp. have prominent ability to suppress plant pathogens and
      corresponding diseases. Previous analyses of Bacillus spp. revealed numerous gene
      clusters involved in nonribosomal synthesis of cyclic lipopeptides with distinct
      antimicrobial action. The 4'-phosphopantetheinyl transferase (PPTase) encoded by
      sfp gene is a key factor in lipopeptide synthesis in Bacillus spp. In previous
      study, B. amyloliquefaciens strain HAB-2 was found to inhibit a broad range of
      plant pathogens, which was attributed to its secondary metabolite lipopeptide.
      RESULTS: A sfp homologue lpaH2 which encoded phosphopantetheinyl transferase but
      shared 71% sequence similarity was detected in strain HAB-2. Disruption of lpaH2
      gene resulted in losing the ability of strain HAB-2 to produce lipopeptide, as
      well as antifungal and hemolytic activities. When lpaH2 replaced sfp gene of B.
      subtilis strain 168, a non-lipopeptide producer, the genetically engineered
      strain 168 could produced lipopeptides and recovered antifungal activity.
      Quantitative PCR assays indicated that, the expression level of lpaH2 in B.
      subtilis 168 strain decrease to 0.27-fold compared that of the wild type B.
      amyloliquefaciens strain HAB-2. CONCLUSION: Few studies have reported about lpa
      gene which can replace sfp gene in the different species. Taken together, our
      study showed for the first time that lpaH2 from B. amyloliquefaciens could
      replace sfp gene.

PMID- 29202701
TI  - Effects of sevoflurane and propofol on the development of pneumonia after
      esophagectomy: a retrospective cohort study.
AB  - BACKGROUND: Postoperative pneumonia (PP) is one of the common complications
      following esophagectomy and associated with poor short- and long-term outcomes.
      Sevoflurane and propofol, which have inflammatory-modulating effects, are common
      used general anesthetics. This study aimed to compare the effects of anesthesia
      with sevoflurane and propofol on the development of PP after esophageal surgery
      for cancer. METHODS: The electronic medical records of patients who underwent
      elective esophagectomy between July 2013 and July 2016 were reviewed. We
      conducted univariate and multivariate logistics analysis and propensity score
      matching analysis to compare the effect of sevoflurane and propofol on the
      incidence of PP and to identify the risk factors for PP after esophagectomy.
      RESULTS: Overall, the incidence of postoperative pneumonia was 9.5%. There was no
      significant difference in the rates of PP between sevoflurane group and propofol
      group either before or after propensity score matching (9.6% vs 8.0%, P = 0.606;
      7.7% vs 6.4%, P = 0.754, respectively). Univariate and multivariate analysis
      revealed that alcohol use (OR 1.513; 95% CI 1.062-2.156), surgical procedure
      (Sweet: referent; Ivor-Lewis: OR 1.993; 95% CI 1.190-3.337; Three-incision: OR
      1.878; 95% CI 1.296-2.722) and surgeon experience (high-volume: referent; low
      volume: OR 1.525; 95% CI 1.090-2.135) were significant risk factors of
      postoperative pneumonia. CONCLUSIONS: Sevoflurane did not differ from propofol in
      terms of affecting the risk of PP development after esophagectomy.

PMID- 29202703
TI  - The ability of left ventricular end-diastolic volume variations measured by TEE
      to monitor fluid responsiveness in high-risk surgical patients during craniotomy:
      a prospective cohort study.
AB  - BACKGROUND: This study was aimed to evaluate the ability of left ventricular end
      diastolic volume variations (LVEDVV) measured by transesophageal echocardiography
      (TEE) compared with stroke volume variation (SVV) obtained by the FloTrac/Vigileo
      monitor to predict fluid responsiveness, in patients undergoing craniotomy with
      goal direct therapy. METHODS: We used SVV obtained by the FloTrac/Vigileo monitor
      to manage intraoperative hypotension in adult patients undergoing craniotomy (ASA
      III - IV) after obtaining IRB approval and informed consent. The LVEDVV were
      measured by TEE through the changes of left ventricular short diameter of axle
      simultaneously. When cardiac index (CI) <= 2.5 and SVV >= 15%, comparisons were
      made between the two devices before and after volume expansion. RESULTS: We
      enrolled twenty-six patients referred for craniotomy in this study and 145 pairs
      of data were obtained. Mean Vigileo-SVV and TEE-LVEDVV were 17.8 +/- 2.78% and
      22.1 +/- 7.25% before volume expansion respectively, and were 10.95 +/- 2.8% and
      13.58 +/- 3.78% after volume expansion respectively (P < 0.001). The relationship
      between Vigileo-SVV and TEE-LVEDVV was significant (r2 = 0.55; p < 0.001).
      Agreement between Vigileo-SVV and TEE-LVEDVV was 3.3% +/- 3.9% (mean bias +/- SD,
      Bland-Altman). CONCLUSIONS: For fluid responsiveness of patients during
      craniotomy in ASA III-IV, LVEDVV measured by left ventricular short diameter of
      axle using M type echocaidiographic measurement seems an acceptable monitoring
      indicator. This accessible method has promising clinical applications in
      situations where volume and cardiac function monitoring is of great importance
      during surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC
      13003583 , August 20, 2013.

PMID- 29202704
TI  - Prevention of tick bites: an evaluation of a smartphone app.
AB  - BACKGROUND: Lyme borreliosis (LB) is the most common reported tick-borne
      infection in Europe, and involves transmission of Borrelia by ticks. As long as a
      vaccine is not available and effective measures for controlling tick populations
      are insufficient, LB control is focused on preventive measures to avoid tick
      bites. To inform citizens about the risk of ticks, motivate them to check for
      tick bites, and encourage them to remove any attached tick as quickly as
      possible, a mobile app called 'Tekenbeet' (Dutch for 'tick bite') was developed
      and released. The aim of this study was to evaluate the usage and user
      satisfaction of the 'Tekenbeet' app and to investigate whether it affects users'
      knowledge, perceived severity, perceived susceptibility, self-efficacy, response
      efficacy, current behavior and intention to comply with preventive measures.
      METHODS: Usage of the app was evaluated with data obtained from Google Analytics.
      A survey among the Dutch general adult population with two data collection
      periods evaluated the usage, user satisfaction and its influence on
      abovementioned outcomes. RESULTS: Data obtained from Google Analytics showed the
      app was downloaded almost 40,000 in the 20 months following the launch. The 'tick
      radar' and 'tick diary' screens were viewed most often. In addition, a total of
      554 respondents completed an online survey. The mean user satisfaction score was
      7.44 (on a scale of 1-10) and 90.9% of respondents would recommend the app to
      others. On average, survey respondents who downloaded the app (n = 243) recorded
      significantly more often higher knowledge scores (OR 3.37; 95% CI 2.02-5.09) and
      had a higher intention to comply with preventive measures (OR 2.47; 95% CI 1.22
      5.85) compared to respondents who did not download the app (n = 311).
      CONCLUSIONS: The 'Tekenbeet' app is a frequently used and well-appreciated
      educational tool to increase public knowledge of ticks and tick bites. It also
      helps to improve the user's intention to apply preventive measures. The use of
      smartphones and apps is now commonplace in the Netherlands; the 'Tekenbeet' app
      feeds into this trend and thereby offers a modern day alternative to established
      formats such as an information leaflet and information provision on the Internet.

PMID- 29202702
TI  - C-reactive protein (CRP) but not the related pentraxins serum amyloid P and PTX3
      inhibits the proliferation and induces apoptosis of the leukemia cell line Mono
      Mac 6.
AB  - BACKGROUND: Pentraxins are a family of highly conserved secreted proteins that
      regulate the innate immune system, including monocytes and macrophages. C
      reactive protein (CRP) is a plasma protein whose levels can rise to 1000 MUg/ml
      from the normal <3 MUg/ ml during inflammation. RESULTS: We find that CRP
      inhibits proliferation of the human myeloid leukemia cell line Mono Mac 6 with an
      IC50 of 75 MUg/ ml by inducing apoptosis of these cells. The related proteins
      serum amyloid P (SAP) and pentraxin 3 (PTX3) do not inhibit Mono Mac 6
      proliferation. CRP has no significant effect on the proliferation of other
      leukemia cell lines such as HL-60, Mono Mac 1, K562, U937, or THP-1, or the
      survival of normal peripheral blood cells. The effect of CRP appears to be
      dependent on the CRP receptor FcgammaRI, and is negatively regulated by a
      phosphatidylinositol -3-kinase pathway. CONCLUSION: These data reveal
      differential signaling by pentraxins on immune cells, and suggest that CRP can
      regulate the proliferation of some myeloid leukemia cells.

PMID- 29202705
TI  - Differences in global gene expression in muscle tissue of Nellore cattle with
      divergent meat tenderness.
AB  - BACKGROUND: Meat tenderness is the consumer's most preferred sensory attribute.
      This trait is affected by a number of factors, including genotype, age, animal
      sex, and pre- and post-slaughter management. In view of the high percentage of
      Zebu genes in the Brazilian cattle population, mainly Nellore cattle, the
      improvement of meat tenderness is important since the increasing proportion of
      Zebu genes in the population reduces meat tenderness. However, the measurement of
      this trait is difficult once it can only be made after animal slaughtering. New
      technologies such as RNA-Seq have been used to increase our understanding of the
      genetic processes regulating quantitative traits phenotypes. The objective of
      this study was to identify differentially expressed genes related to meat
      tenderness, in Nellore cattle in order to elucidate the genetic factors
      associated with meat quality. Samples were collected 24 h postmortem and the meat
      was not aged. RESULTS: We found 40 differentially expressed genes related to meat
      tenderness, 17 with known functions. Fourteen genes were up-regulated and 3 were
      down-regulated in the tender meat group. Genes related to ubiquitin metabolism,
      transport of molecules such as calcium and oxygen, acid-base balance, collagen
      production, actin, myosin, and fat were identified. The PCP4L1 (Purkinje cell
      protein 4 like 1) and BoLA-DQB (major histocompatibility complex, class II, DQ
      beta) genes were validated by qRT-PCR. The results showed relative expression
      values similar to those obtained by RNA-Seq, with the same direction of
      expression (i.e., the two techniques revealed higher expression of PCP4L1 in
      tender meat samples and of BoLA-DQB in tough meat samples). CONCLUSIONS: This
      study revealed the differential expression of genes and functions in Nellore
      cattle muscle tissue, which may contain potential biomarkers involved in meat
      tenderness.

PMID- 29202706
TI  - Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.
AB  - BACKGROUND: Ancient Di-Qiang people once resided in the Ganqing region of China,
      adjacent to the Central Plain area from where Han Chinese originated. While gene
      flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence
      to support this view. Here we analyzed the human remains from an early Di-Qiang
      site (Mogou site dated ~4000 years old) and compared them to other ancient DNA
      across China, including an early Han-related site (Hengbei site dated ~3000 years
      old) to establish the underlying genetic relationship between the Di-Qiang and
      ancestors of Han Chinese. RESULTS: We found Mogou mtDNA haplogroups were highly
      diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10,
      M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup
      O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using
      targeted unique regions on the non-recombining region of the Y-chromosome. We
      compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of
      1793 individuals, and found that Mogou shared close genetic distances with
      Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We
      modeled their interactions using Approximate Bayesian Computation, and support
      was given to a potential admixture of ~13-18% between the Mogou and Northern Han
      around 3300-3800 years ago. CONCLUSIONS: Mogou harbors the earliest genetically
      identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and
      ~70% of its maternal haplogroups could be found in present-day Northern Han
      Chinese.

PMID- 29202707
TI  - Functional SNP allele discovery (fSNPd): an approach to find highly penetrant,
      environmental-triggered genotypes underlying complex human phenotypes.
AB  - BACKGROUND: Significant human diseases/phenotypes exist which require both an
      environmental trigger event and a genetic predisposition before the
      disease/phenotype emerges, e.g. Carbamazepine with the rare SNP allele of
      rs3909184 causing Stevens Johnson syndrome, and aminoglycosides with rs267606617
      causing sensory neural deafness. The underlying genotypes are fully penetrant
      only when the correct environmental trigger(s) occur, otherwise they are silent
      and harmless. Such diseases/phenotypes will not appear to have a Mendelian
      inheritance pattern, unless the environmental trigger is very common (>50% per
      lifetime). The known causative genotypes are likely to be protein-altering SNPs
      with dominant/semi-dominant effect. We questioned whether other diseases and
      phenotypes could have a similar aetiology. METHODS: We wrote the fSNPd program to
      analyse multiple exomes from a test cohort simultaneously with the purpose of
      identifying SNP alleles at a significantly different frequency to that of the
      general population. fSNPd was tested on trial cohorts, iteratively improved, and
      modelled for performance against an idealised association study under mutliple
      parameters. We also assessed the seqeuncing depath of all human exons to
      determine which were sufficiently well sequenced in an exome to be sued by fSNPd 
      by assessing forty exomes base by base. RESULTS: We describe a simple
      methodology for the detection of SNPs capable of causing a phenotype triggered by
      an environmental event. This uses cohorts of relatively small size (30-100
      individuals) with the phenotype being investigated, their exomes, and thence
      seeks SNP allele frequencies significantly different from expected to identify
      potentially clinically important, protein altering SNP alleles. The strengths and
      weaknesses of this approach for discovering significant genetic causes of human
      disease are comparable to Mendelian disease mutation detection and Association
      Studies. CONCLUSIONS: The fSNPd methodology is another approach, and has
      potentially significant advantage over Association studies in needing far fewer
      individuals, to detect genes involved in the pathogenesis of a
      diseases/phenotypes. Furthermore, the SNP alleles identified alter amino acids,
      potentially making it easier to devise functional assays of protein function to
      determine pathogenicity.

PMID- 29202708
TI  - ERDO - a framework to select an appropriate randomization procedure for clinical
      trials.
AB  - BACKGROUND: Randomization is considered to be a key feature to protect against
      bias in randomized clinical trials. Randomization induces comparability with
      respect to known and unknown covariates, mitigates selection bias, and provides a
      basis for inference. Although various randomization procedures have been
      proposed, no single procedure performs uniformly best. In the design phase of a
      clinical trial, the scientist has to decide which randomization procedure to use,
      taking into account the practical setting of the trial with respect to the
      potential of bias. Less emphasis has been placed on this important design
      decision than on analysis, and less support has been available to guide the
      scientist in making this decision. METHODS: We propose a framework that weights
      the properties of the randomization procedure with respect to practical needs of
      the research question to be answered by the clinical trial. In particular, the
      framework assesses the impact of chronological and selection bias on the
      probability of a type I error. The framework is applied to a case study with a 2
      arm parallel group, single center randomized clinical trial with continuous
      endpoint, with no-interim analysis, 1:1 allocation and no adaptation in the
      randomization process. RESULTS: In so doing, we derive scientific arguments for
      the selection of an appropriate randomization procedure and develop a template
      which is illustrated in parallel by a case study. Possible extensions are
      discussed. CONCLUSION: The proposed ERDO framework guides the investigator
      through a template for the choice of a randomization procedure, and provides easy
      to use tools for the assessment. The barriers for the thorough reporting and
      assessment of randomization procedures could be further reduced in the future
      when regulators and pharmaceutical companies employ similar, standardized
      frameworks for the choice of a randomization procedure.

PMID- 29202710
TI  - Parallel loss of introns in the ABCB1 gene in angiosperms.
AB  - BACKGROUND: The presence of non-coding introns is a characteristic feature of
      most eukaryotic genes. While the size of the introns, number of introns per gene
      and the number of intron-containing genes can vary greatly between sequenced
      eukaryotic genomes, the structure of a gene with reference to intron presence and
      positions is typically conserved in closely related species. Unexpectedly, the
      ABCB1 (ATP-Binding Cassette Subfamily B Member 1) gene which encodes a P
      glycoprotein and underlies dwarfing traits in maize (br2), sorghum (dw3) and
      pearl millet (d2) displayed considerable variation in intron composition.
      RESULTS: An analysis of the ABCB1 gene structure in 80 angiosperms revealed that
      the number of introns ranged from one to nine. All introns in ABCB1 underwent
      either a one-time loss (single loss in one lineage/species) or multiple
      independent losses (parallel loss in two or more lineages/species) with the
      majority of losses occurring within the grass family. In contrast, the structure
      of the closest homolog to ABCB1, ABCB19, remained constant in the majority of
      angiosperms analyzed. Using known phylogenetic relationships within the grasses,
      we determined the ancestral branch-points where the losses occurred. Intron 7,
      the longest intron, was lost in only a single species, Mimulus guttatus,
      following duplication of ABCB1. Semiquantitative PCR showed that the M. guttatus
      ABCB1 gene copy without intron 7 had significantly lower transcript levels than
      the gene copy with intron 7. We further demonstrated that intron 7 carried two
      motifs that were highly conserved across the monocot-dicot divide. CONCLUSIONS:
      The ABCB1 gene structure is highly dynamic, while the structure of ABCB19
      remained largely conserved through evolution. Precise removal of introns,
      preferential removal of smaller introns and presence of at least 2 bp of
      microhomology flanking most introns indicated that intron loss may have
      predominantly occurred through non-homologous end-joining (NHEJ) repair of double
      strand breaks. Lack of microhomology in the exon upstream of lost phase I introns
      was likely due to release of the selective constraint on the penultimate base
      (3rd base in codon) of the terminal codon by the splicing machinery. In addition
      to size, the presence of regulatory motifs will make introns recalcitrant to
      loss.

PMID- 29202711
TI  - Design and validation of a German version of the GSRS-IBS - an analysis of its
      psychometric quality and factorial structure.
AB  - BACKGROUND: Currently, a suitable questionnaire in German language is not
      available to monitor the progression and evaluate the severity of irritable bowel
      syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal
      Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to
      evaluate its psychometric qualities and factorial structure. METHODS: This study
      is based on a total sample of 372 participants [62.6% female, mean age = 41 years
      (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were
      receiving treatment for chronic inflammatory bowel disease, 12.1% of the
      participants were recruited from a psychosomatic clinic, and 50.5% belonged to a
      control group. All participants completed the German version of GSRS-IBS (called
      Reizdarm-Fragebogen, RDF), as well as the Giebetaen Subjective Complaints List
      (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D).
      RESULTS: The internal consistency of the RDF total scale was at least
      satisfactory in all subsamples (Cronbach's Alpha between .77 and .92), and for
      all subscales (Cronbach's Alpha between .79 and .91). The item difficulties
      (between .25 and .73) and the item-total correlations (between .48 and .83) were
      equally satisfactory. Principal axis analysis revealed a four-factorial structure
      of the RDF items, which mainly resembled the structure of the English original.
      Convergent validity was established based on substantial and significant
      correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01)
      and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of
      the HADS-D. CONCLUSION: The German version of the GSRS-IBS RDF proves to be an
      effective, reliable, and valid questionnaire for the assessment of symptom
      severity in IBS, which can be used in clinical practice as well as in clinical
      studies.

PMID- 29202709
TI  - Transcriptomic and metabolic responses of Calotropis procera to salt and drought
      stress.
AB  - BACKGROUND: Calotropis procera is a wild plant species in the family Apocynaceae
      that is able to grow in harsh, arid and heat stressed conditions. Understanding
      how this highly adapted plant persists in harsh environments should inform future
      efforts to improve the hardiness of crop and forage plant species. To study the
      plant response to droMUght and osmotic stress, we treated plants with
      polyethylene glycol and NaCl and carried out transcriptomic and metabolomics
      measurements across a time-course of five days. RESULTS: We identified a highly
      dynamic transcriptional response across the time-course including dramatic
      changes in inositol signaling, stress response genes and cytokinins. The
      resulting metabolome changes also involved sharp increases of myo-inositol, a key
      signaling molecule and elevated amino acid metabolites at later times.
      CONCLUSIONS: The data generated here provide a first glimpse at the expressed
      genome of C. procera, a plant that is exceptionally well adapted to arid
      environments. We demonstrate, through transcriptome and metabolome analysis that
      myo-inositol signaling is strongly induced in response to drought and salt stress
      and that there is elevation of amino acid concentrations after prolonged osmotic
      stress. This work should lay the foundations of future studies in adaptation to
      arid environments.

PMID- 29202712
TI  - Global gene expression reveals stress-responsive genes in Aspergillus fumigatus
      mycelia.
AB  - BACKGROUND: Aspergillus fumigatus is a human fungal pathogen that causes
      aspergillosis in immunocompromised hosts. A. fumigatus is believed to be exposed
      to diverse environmental stresses in the host cells. The adaptation mechanisms
      are critical for infections in human bodies. Transcriptional networks in response
      to diverse environmental challenges remain to be elucidated. To gain insights
      into the adaptation to environmental stresses in A. fumigatus mycelia, we
      conducted time series transcriptome analyses. RESULTS: With the aid of RNA-seq,
      we explored the global gene expression profiles of mycelia in A. fumigatus upon
      exposure to diverse environmental changes, including heat, superoxide, and
      osmotic stresses. From the perspective of global transcriptomes, transient
      responses to superoxide and osmotic stresses were observed while responses to
      heat stresses were gradual. We identified the stress-responsive genes for
      particular stresses, and the 266 genes whose expression levels drastically
      fluctuated upon exposure to all tested stresses. Among these, the 77
      environmental stress response genes are conserved in S. cerevisiae, suggesting
      that these genes might be more general prerequisites for adaptation to
      environmental stresses. Finally, we revealed the strong correlations among
      expression profiles of genes related to 'rRNA processing'. CONCLUSIONS: The time
      series transcriptome analysis revealed the stress-responsive genes underlying the
      adaptation mechanisms in A. fumigatus mycelia. These results will shed light on
      the regulatory networks underpinning the adaptation of the filamentous fungi.

PMID- 29202714
TI  - Improving quality of care for maternal and newborn health: a pre-post evaluation
      of the Safe Childbirth Checklist at a hospital in Bangladesh.
AB  - BACKGROUND: Bangladesh has achieved major gains in maternal and newborn survival,
      facility childbirth and skilled birth attendance between 1991 and 2010, but
      excess maternal mortality persists. High-quality maternal health care is
      necessary to address this burden. Implementation of WHO Safe Childbirth Checklist
      (SCC), whose items address the major causes of maternal deaths, is hypothesized
      to improve adherence of providers to essential childbirth practices. METHOD: The
      SCC was adapted for the local context through expert consultation meetings,
      creating a total of 27 checklist items. This study was a pre-post evaluation of
      SCC implementation. Data were collected over 8 months at Magura District
      Hospital. We analysed 468 direct observations of birth (main analysis using 310
      complete observations and sensitivity analysis with the additional 158 incomplete
      observations) from admission to discharge. The primary outcome of interest was
      the number of essential childbirth practices performed before compared to after
      SCC implementation. The change was assessed using adjusted Poisson regression
      models accounting for clustering by nurse-midwives. RESULT: After checklist
      introduction, significant improvements were observed: on average, around 70% more
      of these safe childbirth practices were performed in the follow-up period
      compared to baseline (from 11 to 19 out of 27 practices). Substantial increases
      were seen in communication between nurse-midwives and mothers (counselling), and
      in management of complications (including rational use of medicines). In
      multivariable models that included characteristics of the mothers and of the
      nurse-midwives, the rate of delivering the essential childbirth practices was
      1.71 times greater in the follow-up compared to baseline (95% CI 1.61-1.81).
      CONCLUSION: Implementation of SCC has the potential to improve essential
      childbirth practice in resource-poor settings like Bangladesh. This study
      emphasizes the need for health system strengthening in order to achieve the full
      advantages of SCC implementation.

PMID- 29202713
TI  - IntroMap: a signal analysis based method for the detection of genomic
      introgressions.
AB  - BACKGROUND: Breeding programs often rely on marker-assisted tests or variant
      calling of next generation sequence (NGS) data to identify regions of genomic
      introgression arising from the hybridization of two plant species. In this paper
      we present IntroMap, a bioinformatics pipeline for the screening of candidate
      plants through the application of signal processing techniques to NGS data, using
      alignment to a reference genome sequence (annotation is not required) that shares
      homology with the recurrent parental cultivar, and without the need for de novo
      assembly of the read data or variant calling. RESULTS: We show the accurate
      identification of introgressed genomic regions using both in silico simulated
      genomes, and a hybridized cultivar data set using our pipeline. Additionally we
      show, through targeted marker-based assays, validation of the IntroMap predicted
      regions for the hybrid cultivar. CONCLUSIONS: This approach can be used to
      automate the screening of large populations, reducing the time and labor
      required, and can improve the accuracy of the detection of introgressed regions
      in comparison to a marker-based approach. In contrast to other approaches that
      generally rely upon a variant calling step, our method achieves accurate
      identification of introgressed regions without variant calling, relying solely
      upon alignment.

PMID- 29202715
TI  - Epidemiology of influenza in West Africa after the 2009 influenza A(H1N1)
      pandemic, 2010-2012.
AB  - BACKGROUND: Over the last decade, capacity for influenza surveillance and
      research in West Africa has strengthened. Data from these surveillance systems
      showed influenza A(H1N1)pdm09 circulated in West Africa later than in other
      regions of the continent. METHODS: We contacted 11 West African countries to
      collect information about their influenza surveillance systems (number of sites,
      type of surveillance, sampling strategy, populations sampled, case definitions
      used, number of specimens collected and number of specimens positive for
      influenza viruses) for the time period January 2010 through December 2012.
      RESULTS: Of the 11 countries contacted, 8 responded: Burkina Faso, Cote d'Ivoire,
      Mali, Mauritania, Niger, Nigeria, Sierra Leone and Togo. Countries used standard
      World Health Organization (WHO) case definitions for influenza-like illness (ILI)
      and severe acute respiratory illness (SARI) or slight variations thereof. There
      were 70 surveillance sites: 26 SARI and 44 ILI. Seven countries conducted SARI
      surveillance and collected 3114 specimens of which 209 (7%) were positive for
      influenza viruses. Among influenza-positive SARI patients, 132 (63%) were
      influenza A [68 influenza A(H1N1)pdm09, 64 influenza A(H3N2)] and 77 (37%) were
      influenza B. All eight countries conducted ILI surveillance and collected 20,375
      specimens, of which 2278 (11%) were positive for influenza viruses. Among
      influenza-positive ILI patients, 1431 (63%) were influenza A [820 influenza
      A(H1N1)pdm09, 611 influenza A(H3N2)] and 847 (37%) were influenza B. A majority
      of SARI and ILI case-patients who tested positive for influenza (72% SARI and 59%
      ILI) were children aged 0-4 years, as were a majority of those enrolled in
      surveillance. The seasonality of influenza and the predominant influenza type or
      subtype varied by country and year. CONCLUSIONS: Influenza A(H1N1)pdm09 continued
      to circulate in West Africa along with influenza A(H3N2) and influenza B during
      2010-2012. Although ILI surveillance systems produced a robust number of samples
      during the study period, more could be done to strengthen surveillance among
      hospitalized SARI case-patients. Surveillance systems captured young children but
      lacked data on adults and the elderly. More data on risk groups for severe
      influenza in West Africa are needed to help shape influenza prevention and
      clinical management policies and guidelines.

PMID- 29202716
TI  - Prediction of postoperative inflammatory complications after esophageal cancer
      surgery based on early changes in the C-reactive protein level in patients who
      received perioperative steroid therapy and enhanced recovery after surgery care:
      a retrospective analysis.
AB  - BACKGROUND: Serum C-reactive protein (CRP) level can be an indicator of the early
      stage of infectious complications. However, its utility in advanced esophageal
      cancer patients who receive radical esophagectomy with two- or three-field lymph
      node dissection with perioperative steroid therapy and enhanced recovery after
      surgery (ERAS) care is unclear. METHODS: The present study retrospectively
      examined 117 consecutive esophageal cancer patients who received neoadjuvant
      chemotherapy followed by radical esophagectomy. All patients received
      perioperative steroid therapy and ERAS care. The utility of the CRP value in the
      early detection of serious infectious complications (SICs) was evaluated based on
      the area under the receiver operating characteristic curve (AUC). Univariate and
      multivariate logistic regression analyses were performed to identify the risk
      factors for SICs. RESULTS: SICs were observed in 20 patients (17.1%). The CRP
      level on postoperative day (POD) 4 had superior diagnostic accuracy for SICs (AUC
      0.778). The cut-off value for CRP was determined to be 4.0 mg/dl. A multivariate
      analysis identified CRP >= 4.0 mg/dl on POD 4 (odds ratio, 18.600; 95% confidence
      interval [CI], 4.610-75.200) and three-field lymph node dissection (odds ratio,
      7.950; 95% CI, 1.900-33.400) as independent predictive factors. CONCLUSIONS: CRP
      value on POD 4 may be useful for predicting SICs in esophageal cancer patients
      who receive radical esophagectomy with perioperative steroid therapy and ERAS
      care. This result may encourage the performance of imaging studies to detect the
      focus and thereby lead to the early medical and/or surgical intervention to
      improve short-term outcomes.

PMID- 29202717
TI  - Ten years follow-up after surgery for a foveal detachment due to optic disc pit:
      a case report of outer retinal layer healing.
AB  - BACKGROUND: To report a case of complete progressive visual recovery and healing
      of outer retinal layers after vitrectomy for foveal detachment associated with
      optic disc pit. CASE PRESENTATION: Optical coherence tomography (OCT) follow-up
      was performed on a 15-year-old boy with deep optic disc pit and foveal
      detachment, before and for 10 years after vitrectomy with gas. The foveal
      detachment was successfully reattached with complete reapplication of the retina.
      OCT scans showed a progressive long-term retinal healing with reappearance of the
      ellipsoid line and visual acuity improved from 20/100 before surgery to 20/25, 10
      years after surgery. CONCLUSIONS: Photoreceptor regeneration after foveal
      detachment surgery has been already described only in zebrafish but never humans.
      However, we highlight with this case that in humans, a healing process of the
      outer retinal layers can occur with reappearance of the ellipsoid zone on OCT.
      This healing process may take several years and allow a complete functional
      restoration.

PMID- 29202718
TI  - Google as a cancer control tool in Queensland.
AB  - BACKGROUND: Recent advances in methodologies utilizing "big data" have allowed
      researchers to investigate the use of common internet search engines as a real
      time tool to track disease. Little is known about its utility with tracking
      cancer incidence. This study aims to investigate the potential correlates of
      monthly internet search volume indexes (SVIs) and observed monthly age
      standardised incidence rates (ASRs) for breast cancer, colorectal cancer,
      melanoma and prostate cancer. METHODS: The monthly ASRs for the four cancers in
      Queensland were calculated using data from the Queensland Cancer Registry between
      January 2006 and December 2012. The monthly SVIs of the respective cancer search
      terms in Queensland were accessed from Google Trends for the same period. A time
      series seasonal decomposition method was performed to detect the seasonal
      patterns of SVIs and ASRs. Pearson's correlation coefficient and time series
      cross-correlation analysis were used to assess the associations between SVIs and
      ASRs. Linear regression models were used to examine the power of SVIs to predict
      monthly in ASRs. RESULTS: Increases in the monthly ASRs of the four cancers were
      significantly correlated with increases in the monthly SVIs of the respective
      cancers except for colorectal cancer. The predictive power of the SVIs to explain
      variances in the corresponding ASRs varied by cancer type, with the percent
      explained ranging from 5.6% for breast cancer to 17.9% for skin cancer (SVI) with
      melanoma (ASR). Some improvement in the variation explained was obtained by
      including more search terms or lagged SVIs for the respective cancers in the
      linear regression models. The seasonal analysis indicated that the SVIs peaked
      periodically at around their respective cancer awareness months. CONCLUSIONS:
      Using SVIs from a popular internet search engine was only able to explain a small
      portion of changes in the respective ASRs. While an expanded regression model
      explained a higher proportion of variability, the interpretation of this was
      difficult. Further development and refinement of this approach will be needed
      before search-based cancer surveillance can provide useful information regarding
      resource deployment to guide cancer control and track the impact of cancer
      awareness and education programmes.

PMID- 29202719
TI  - An in vitro splicing assay reveals the pathogenicity of a novel intronic variant
      in ATP6V0A4 for autosomal recessive distal renal tubular acidosis.
AB  - BACKGROUND: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare
      hereditary disease caused by pathogenic variants in the ATP6V0A4 gene or ATP6V1B1
      gene, and characterized by hyperchloremic metabolic acidosis with normal anion
      gap, hypokalemia, hypercalciuria, hypocitraturia and nephrocalcinosis. Although
      several intronic nucleotide variants in these genes have been detected, all of
      them fell in the apparent splice consensus sequence. In general, transcriptional
      analysis is necessary to determine the effect on function of the novel intronic
      variants located out of splicing consensus sequences. In recent years, functional
      splicing analysis using minigene construction was used to assess the
      pathogenicity of novel intoronic variant in various field. METHODS: We
      investigated a sporadic case of dRTA with a compound heterozygous mutation in the
      ATP6V0A4 gene, revealed by next generation sequencing. One variant was already
      reported as pathogenic; however, the other was a novel variant in intron 11
      (c.1029 + 5G > A) falling outside of the apparent splicing consensus sequence.
      Expression of ATP6V0A4 was not detected in peripheral leukocytes by RT-PCR
      analysis. Therefore, an in vitro functional splicing study using minigene
      construction was conducted to analyze the splicing pattern of the novel variant.
      RESULTS: A minigene assay revealed that the novel intronic variant leads to a 104
      bp insertion immediately following exon 11. In addition, this result was
      confirmed using RNA extracted from the patient's cultured leukocytes. CONCLUSION:
      These results proved the pathogenicity of a novel intronic variant in our
      patient. We concluded that the minigene assay is a useful, non-invasive method
      for functional splicing analysis of inherited kidney disease, even if standard
      transcriptional analysis could not detect abnormal mRNA.

PMID- 29202720
TI  - High-precision radiotherapy of motor deficits due to metastatic spinal cord
      compression (PRE-MODE): a multicenter phase 2 study.
AB  - BACKGROUND: For metastatic spinal cord compression (MSCC), conventional
      radiotherapy with 10 * 3 Gy in 2 weeks results in better local progression-free
      survival (LPFS) than 5 * 4 Gy in 1 week. Since patients with MSCC are often
      significantly impaired, an overall treatment time of 1 week would be preferable
      if resulting in similar outcomes as longer programs. This may be achieved with 5
      * 5 Gy in 1 week, since the biologically effective dose is similar to 10 * 3 Gy.
      It can be expected that 5 * 5 Gy (like 10 * 3) Gy results in better LPFS than 5 *
      4 Gy in 1 week. METHODS/DESIGN: This phase 2 study investigates LPFS after high
      precision RT with 5 * 5 Gy in 1 week. LPFS is defined as freedom from both
      progression of motor deficits during RT and new or progressive motor deficits dur
      to an in-field recurrence of MSCC following RT. Considering the tolerance dose of
      the spinal cord, 5 * 5 Gy can be safely administered with high-precision
      radiotherapy such as volumetric modulated arc therapy (VMAT) or stereotactic body
      radiotherapy (SBRT). Maximum dose to the spinal cord should not exceed 101.5% of
      the prescribed dose to keep the risk of radiation myelopathy below 0.03%. Primary
      endpoint is LPFS at 6 months following radiotherapy; secondary endpoints include
      motor function/ability to walk, sensory function, sphincter dysfunction, LPFS
      directly and 1 and 3 months following radiotherapy, overall survival, pain
      relief, quality of life and toxicity. Follow-up visits will be performed directly
      and at 1, 3 and 6 months following radiotherapy. After completion of this phase 2
      study, patients will be compared to a historical control group receiving
      conventional radiotherapy with 5 * 4 Gy in 1 week. Forty-four patients will be
      included assuming 5 * 5 Gy will provide the same benefit in LPFS when compared to
      5 * 4 Gy as reported for 10 * 3 Gy. DISCUSSION: If superiority regarding LPFS is
      shown for high-precision radiotherapy with 5 * 5 Gy when compared to conventional
      radiotherapy with 5 * 4 Gy, patients with MSCC would benefit from 5 * 5 Gy, since
      high LPFS rates could be achieved with 1 week of radiotherapy instead of 2 weeks
      (10 * 3 Gy). TRIAL REGISTRATION: clinicaltrials.gov NCT03070431 . Registered 27
      February 2017.

PMID- 29202721
TI  - Portable acuity screening for any school: validation of patched HOTV with
      amblyopic patients and Bangerter normals.
AB  - BACKGROUND: We needed to validate and calibrate our portable acuity screening
      tools so amblyopia could be detected quickly and effectively at school entry.
      METHODS: Spiral-bound flip cards and download pdf surround HOTV acuity test box
      with critical lines were combined with a matching card. Amblyopic patients
      performed critical line, then threshold acuity which was then compared to patched
      E-ETDRS acuity. 5 normal subjects wore Bangerter foil goggles to simulate blur
      for comparative validation. RESULTS: The 31 treated amblyopic eyes showed: logMAR
      HOTV = 0.97(logMAR E-ETDRS)-0.04 r2 = 0.88. All but two (6%) fell less than 2
      lines difference. The five showed logMAR HOTV = 1.09 ((logMAR E-ETDRS) + .15 r2 =
      0.63. The critical-line, test box was 98% efficient at screening within one line
      of 20/40. CONCLUSION: These tools reliably detected acuity in treated amblyopic
      patients and Bangerter blurred normal subjects. These free and affordable tools
      provide sensitive screening for amblyopia in children from public, private and
      home schools. Changing "pass" criteria to 4 out of 5 would improve sensitivity
      with somewhat slower testing for all students.

PMID- 29202722
TI  - Eradication of P. aeruginosa biofilm in endotracheal tubes based on lock therapy:
      results from an in vitro study.
AB  - BACKGROUND: Despite the several strategies available for the management of
      biofilm-associated ventilator-associated pneumonia, data regarding the efficacy
      of applying antibiotics to the subglottic space (SS) are scarce. We created an in
      vitro model to assess the efficacy of antibiotic lock therapy (ALT) applied in
      the SS for eradication of Pseudomonas aeruginosa biofilm in endotracheal tubes
      (ETTs). METHODS: We applied 2 h of ALT to a P. aeruginosa biofilm in ETTs using a
      single dose (SD) and a 5-day therapy model (5D). We used sterile saline lock
      therapy (SLT) as the positive control. We compared colony count and the
      percentage of live cells between both models. RESULTS: The median (IQR) cfu
      counts/ml and percentage of live cells in the SD-ALT and SD-SLT groups were,
      respectively, 3.12 * 105 (9.7 * 104-0) vs. 8.16 * 107 (7.0 * 107-0) (p = 0.05)
      and 53.2% (50.9%-57.2%) vs. 91.5% (87.3%-93.9%) (p < 0.001). The median (IQR) cfu
      counts/ml and percentage of live cells in the 5D-ALT and 5D-SLT groups were,
      respectively, 0 (0-0) vs. 3.2 * 107 (2.32 * 107-0) (p = 0.03) and 40.6% (36.6%
      60.0%) vs. 90.3% (84.8%-93.9%) (p < 0.001). CONCLUSION: We demonstrated a
      statistically significant decrease in the viability of P. aeruginosa biofilm
      after application of 5D-ALT in the SS. Future clinical studies to assess ALT in
      patients under mechanical ventilation are needed.

PMID- 29202724
TI  - EpCAM expression in squamous cell carcinoma of the uterine cervix detected by
      monoclonal antibody to the membrane-proximal part of EpCAM.
AB  - BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is a promising biomarker
      for squamous cell carcinoma (SCC) of the uterine cervix, because it is over
      expressed in various cancers of epithelial origin. However, EpCAM expression
      reported in previous immunohistochemistry (IHC) studies was inconsistent. We
      hypothesize that the membrane-distal part of EpCAM may be lost during tissue
      preparation, leaving only the membrane-proximal part of EpCAM available for
      antibody binding and IHC staining. METHODS: Two new anti-EpCAM MAbs to the
      membrane-proximal part (WC-2) and the membrane-distal part (WC-1) of EpCAM were
      generated and characterized. WC-2 was selected for its ability to detect EpCAM in
      cervical tissues by IHC. One hundred thirty-five archival paraffin-embedded
      tissues previously diagnosed as cervical SCC (n=44), high-grade (HSIL) (n=43), or
      low-grade (LSIL) (n=48) squamous intraepithelial lesions were examined. IHC score
      was collected, recorded, and analyzed for distribution, intensity, and percentage
      of cancer cells stained for EpCAM. RESULTS: EpCAM expression was consistently
      detected on cervical tissues by WC-2, but not by WC-1. EpCAM was expressed with
      high IHC score in the majority of cervical SCC (37/44), but not in normal
      epithelial area adjacent to SCC. EpCAM was also highly expressed on precancerous
      lesion of the cervix, particularly in HSIL. More importantly, EpCAM expression
      could be used to distinguish between HSIL and LSIL, according to staining
      distribution. HSIL tissues displayed EpCAM expression in two-thirds to full
      thickness of the epithelium, while in LSIL the staining was limited to the lower
      one-third of the thickness. The IHC score of EpCAM expression was strongly
      correlated with cervical cancer and grades of precancerous lesions (r=0.875,
      p<0.001). CONCLUSION: Only the anti-EpCAM MAb to the membrane-proximal part is
      able to detect EpCAM on paraffin-embedded cervical cancer tissues. A strong
      positive correlation between EpCAM expression level and the grades of SILs
      provides the possibility that EpCAM can be used to predict prognosis and severity
      in these patients.

PMID- 29202723
TI  - Changes in urinary risk profile after short-term low sodium and low calcium diet
      in recurrent Swiss kidney stone formers.
AB  - BACKGROUND: Kidney stone disease is common in industrialized countries. Recently,
      it has attracted growing attention, because of its significant association with
      adverse renal outcomes, including end stage renal disease. Calcium-containing
      kidney stones are frequent with high recurrence rates. While hypercalciuria is a
      well-known risk factor, restricted intake of animal protein and sodium, combined
      with normal dietary calcium, has been shown to be more effective in stone
      prevention compared with a low-calcium diet. Notably, the average sodium intake
      in Switzerland is twice as high as the WHO recommendation, while the intake of
      milk and dairy products is low. METHODS: We retrospectively analyzed Swiss
      recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in
      combination with a low-calcium diet on the urinary risk profile. In patients with
      recurrent calcium oxalate containing stones, we investigated both, the
      consequence of a low-sodium diet on urinary volume and calcium excretion, and the
      influence of a low-sodium low-calcium diet on urinary oxalate excretion. RESULTS:
      Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at
      baseline. The diet resulted in a highly significant reduction in 24-h urinary
      sodium and calcium excretion: from 201 +/- 89 at baseline to 128 +/- 88 mmol/d
      for sodium (p < 0.0001), and from 5.67 +/- 3.01 to 4.06 +/- 2.46 mmol/d (p <
      0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no
      increase in oxalate excretion occurred on the restricted diet (0.39 +/- 0.26 vs
      0.39 +/- 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation)
      values were only predictive for the risk of calcium phosphate stones. CONCLUSION:
      A diet low in sodium and calcium in recurrent calcium oxalate stone formers
      resulted in a significant reduction of urinary calcium excretion, but no change
      in urine volume. In this population with apparently low intake of dairy products,
      calcium restriction does not necessarily result in increased urinary oxalate
      excretion. However, based on previous studies, we recommend a normal dietary
      calcium intake to avoid a potential increase in urinary oxalate excretion and
      unfavorable effects on bone metabolism in hypercalciuric KSFs.

PMID- 29202725
TI  - Complete occlusion of anterior capsulorhexis after uneventful cataract surgery,
      treated with YAG laser capsulotomy.
AB  - BACKGROUND: Capsular contraction syndrome (CCS) has been reported as an uncommon
      complication after an cataract extraction surgery with intact anterior
      capsulorhexis. This report is written to present a case of complete occlusion of
      the anterior capsulorhexis opening after an uneventful cataract surgery, which
      was treated with non-invasive treatment. CASE PRESENTATION: A 69-year-old woman
      complained of decreased visual acuity in her right eye, which had started 2
      months ago. She underwent phacoemulsification with an uneventful anterior
      capsulorhexis before 3 months. A total occlusion of the anterior capsulorhexis
      opening with capsular phimosis was identified on slit-lamp biomicroscopy, and a
      circular anterior capsulotomy using neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser was performed immediately. The capsulotomy site remained clear
      after a couple of years. CONCLUSIONS: It is supposed that proliferation of
      fibrotic tissue was relatively prominent in this case, rather than the appearance
      of capsular phimosis. This case can be an uncommon showing a total occlusion of
      the anterior capsulorhexis opening with prominent fibrotic proliferation pattern
      after an uneventful cataract surgery. Additionally, the occlusion could be
      removed with a non-invasive procedure, and was maintained clearly for several
      years.

PMID- 29202726
TI  - Large reductions in cesarean delivery rates in China: a qualitative study on
      delivery decision-making in the era of the two-child policy.
AB  - BACKGROUND: In 2010, China's cesarean delivery (CD) rates increased to one of the
      highest in the world, a significant proportion of which were without medical
      indication. However, recent studies have indicated some declines, coinciding with
      national and local efforts to promote vaginal birth, as well as the relaxation of
      the one-child policy. Considering these trends, we aimed to qualitatively explore
      attitudes towards childbirth and experiences of delivery decision-making among
      women and physicians. METHODS: Semi-structured interviews were conducted with 45
      postpartum women and 7 healthcare providers at one county-level and one
      provincial-level maternity hospital in Zhejiang Province. We also collected
      routine data from 2007 to 2016 and observed doctor-patient interactions and
      hospital facilities as context for the interviews. Interviews were recorded,
      translated and transcribed into English, and then analyzed using a framework
      approach. RESULTS: From 2007 to 2016, cesarean delivery rates at the county-level
      and provincial-level hospital decreased from 46% to 32% and 68% to 44%,
      respectively. For low-risk women, vaginal birth was the primary choice of
      delivery method, encouraged by doctors and nurse-midwives. Elective CD was not as
      widely accepted, in contrast to previous years. Women were aware of and took into
      consideration the consequences of CD for future pregnancies. Among those who
      delivered vaginally, women viewed the existing pain relief methods, epidurals and
      transcutaneous electrical nerve stimulation, with caution or uncertainty. Even
      when requested, epidurals were only given under certain circumstances. For
      multiparas with previous CD, repeat CD remains the norm. Both women and
      professionals were cautious about vaginal birth after cesarean delivery (VBAC)
      given the associated risks. CONCLUSION: In China, changes in family planning
      policy and efforts to promote vaginal birth have greatly changed the culture of
      delivery decision-making, leading to decreased CD rates. This demonstrates the
      powerful role social factors and public policy can play, and provides a model for
      other countries with high CD rates. Further research should explore changes in
      other reproductive decisions during this new multiparous era, particularly across
      provinces.

PMID- 29202727
TI  - Atrial fibrillation is not uncommon among patients with ischemic stroke and
      transient ischemic stroke in China.
AB  - BACKGROUND: Atrial fibrillation (AF) is reported to be a less frequent cause of
      ischemic stroke in China than in Europe and North America, but it is not clear
      whether this is due to underestimation. Our aim was to define the true frequency
      of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF
      in Chinese stroke patients, and to elucidate predictors of newly detected AF.
      METHODS: Patients with acute ischemic stroke or transient ischemic attack (TIA)
      were enrolled in a prospective, multicenter cohort study of 6-day Holter
      monitoring within 7 days after stroke onset at 20 sites in China between 2013 and
      2015. Independent predictors of newly-detected AF were determined by multivariate
      analysis. RESULTS: Among 1511 patients with ischemic stroke and TIA (mean age 63
      years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF
      newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring
      (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5),
      advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI,
      1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13),
      together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were
      independently associated with newly-detected AF. CONCLUSIONS: Contrary to
      previous reports, AF-associated stroke is frequent (20%) in China if systemically
      sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF
      detection in patients with recent ischemic stroke and TIA in China. Advanced age,
      history of heart failure, and higher admission NIHSS and higher level of HDL were
      independent indicators of newly-detected AF. TRIAL REGISTRATION: NCT02156765
      (June 5, 2014).

PMID- 29202728
TI  - Non-tunneled versus tunneled dialysis catheters for acute kidney injury requiring
      renal replacement therapy: a prospective cohort study.
AB  - BACKGROUND: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is
      associated with high morbidity, mortality and resource utilization. The type of
      vascular access placed for AKI-RRT is an important decision, for which there is a
      lack of evidence-based guidelines. METHODS: We conducted a prospective cohort
      study over a 16-month period with 154 patients initiated on AKI-RRT via either a
      non-tunneled dialysis catheter (NTDC) or a tunneled dialysis catheter (TDC) at an
      academic hospital. We compared differences in renal replacement delivery and
      mechanical and infectious outcomes between NTDCs and TDCs. RESULTS: Patients who
      received TDCs had significantly better RRT delivery, both with continuous
      venovenous hemofiltration (CVVH) and intermittent hemodialysis (IHD), compared to
      patients who received NTDCs; these findings were confirmed after multivariable
      adjustment for AKI-specific disease severity score, history of chronic kidney
      disease, renal consult team, and AKI cause. In CVVH and IHD, the median venous
      and arterial blood flow pressures were significantly higher with TDCs compared to
      NTDCs (p < 0.001). Additionally for CVVH, the median number of interruptions per
      catheter was higher with NTDCs compared to TDCs (Rate Ratio (RR) 2.7; p < 0.001),
      and for IHD, a higher median blood flow was seen with TDCs (p < 0.001). There
      were a significantly higher number of mechanical complications with NTDCs (RR
      13.6 p = 0.001). No significant difference was observed between TDCs and NTDCs
      for positive blood cultures per catheter. CONCLUSIONS: Compared to NTDCs, TDCs
      for patients with AKI-RRT had improved RRT delivery and fewer mechanical
      complications. Initial TDC placement for AKI-RRT should be considered when not
      clinically contraindicated given the potential for improved RRT delivery and
      outcomes.

PMID- 29202729
TI  - Changes in prevalence and perinatal outcomes of congenital hydrocephalus among
      Chinese newborns: a retrospective analysis based on the hospital-based birth
      defects surveillance system.
AB  - BACKGROUND: Little is known about the epidemiology of congenital hydrocephalus
      (CH) in China. This study aimed to depict recent changes in CH prevalence and
      perinatal outcomes of the affected newborns. METHODS: Data were obtained from the
      Chinese Birth Defects Monitoring Network (CBDMN), which collects demographic
      information on all newborns above 28 weeks of gestation, and clinical information
      on neonates with congenital anomalies. CH cases delivered during 2005-2012 were
      analyzed. Poisson regression was used to calculate prevalence ratios (PR) and 95%
      confidence intervals, and linear chi-square test was used to examine time trend
      of CH prevalence. RESULTS: Five thousand two hundred forty-five isolated and 1245
      associated CH cases were identified among 10,574,061 newborns, yielding the
      prevalence of 4.96, 1.18 and 6.14 per 10,000 births for the isolated, associated
      and overall hydrocephalus, respectively. The annual prevalence of CH presented a
      decreasing trend (from 7.52 to 5.98 per 10,000 births, P < 0.001). Higher
      prevalence was found in both younger (<20 years, PR: 1.81, 95% CI: 1.56-2.10) and
      older (>=35 years, PR: 1.48, 95% CI: 1.36-1.61) maternal-age groups in comparison
      with the maternal-age group of 20 to 24 years. Higher prevalence was also found
      in infants born to mothers resided in rural areas, male infants, and multiple
      births. Of non-aborted infants with congenital hydrocephalus, 38.11% were born
      with low birth weight, 37.53% were preterm birth, and 20.69% died within 7 days
      after birth. CONCLUSIONS: Our findings present a relatively high prevalence and
      poor perinatal outcomes of CH in China, which can serve as a baseline for future
      study.

PMID- 29202730
TI  - Selection bias in clinical stroke trials depending on ability to consent.
AB  - BACKGROUND: Clinical trials are the hallmark of evidence-based medicine, but
      recruitment is often challenging, especially in stroke trials investigating
      patients not being able to give informed consent. In some nations, ethics
      committees will not approve of inclusion in a clinical study via consent of a
      legal representative. The ethical dilemma of including or excluding those
      patients has not been properly addressed, as there is little data on the effect
      of stroke characteristics on the ability to give informed consent. METHODS: To
      examine differences between patients able and unable to consent at inclusion to
      an acute stroke trial, we conducted a post-hoc analysis of monitoring records
      from a multicentric interventional trial. These records listed patients who gave
      informed consent by themselves and those who needed a legal representative to do
      so. This exemplary STRAWINSKI trial aimed at improving stroke outcome by
      biomarker-guided antibiotic treatment of stroke associated pneumonia and included
      patients within 40 h after stroke onset, suffering from MCA infarctions with an
      NIHSS score > 9 at admission. Standard descriptive and associative statistics
      were calculated to compare baseline characteristics and outcome measures between
      patients who were able to consent and those who were not. RESULTS: We identified
      the person giving consent in 228 out of 229 subjects. Patients with inability to
      consent were older (p < 0.01), suffered from more left-hemispheric (p < 0.01) and
      more severe strokes (NIHSS, p < 0.01), were more likely to die during
      hospitalisation (p < 0.01) or have unfavourable outcome at discharge (mRS, p <
      0.01), to develop fever (p < 0.01) and tended to be more susceptible to
      infections (p = 0.06) during the acute course of the disorder. CONCLUSIONS:
      Demographics, stroke characteristics and outcomes significantly affect stroke
      patients in their ability to consent. Where selection criteria and primary
      outcome measures of a trial are significantly affected by ability to consent,
      excluding patients unable to consent might be unethical. TRIAL REGISTRATION: URL
      http://www.clinicaltrials.gov . Unique identifier: NCT01264549 .

PMID- 29202731
TI  - Economic evaluation of emergency obstetric care training: a systematic review.
AB  - BACKGROUND: Training healthcare providers in Emergency Obstetric Care (EmOC) has
      been shown to be effective in improving their capacity to provide this critical
      care package for mothers and babies. However, little is known about the costs and
      cost-effectiveness of such training. Understanding costs and cost-effectiveness
      is essential in guaranteeing value-for-money in healthcare spending. This study
      systematically reviewed the available literature on cost and cost-effectiveness
      of EmOC trainings. METHODS: Peer-reviewed and grey literature was searched for
      relevant papers published after 1990. Studies were included if they described an
      economic evaluation of EmOC training and the training cost data were available.
      Two reviewers independently searched, screened, and selected studies that met the
      inclusion criteria, with disagreements resolved by a third reviewer. Quality of
      studies was assessed using the Consolidated Health Economic Evaluation Reporting
      Standards statement. For comparability, all costs in local currency were
      converted to International dollar (I$) equivalents using purchasing power parity
      conversion factors. The cost per training per participant was calculated.
      Narrative synthesis was used to summarise the available evidence on cost
      effectiveness. RESULTS: Fourteen studies (five full and nine partial economic
      evaluations) met the inclusion criteria. All five and two of the nine partial
      economic evaluations were of high quality. The majority of studies (13/14) were
      from low- and middle-income countries. Training equipment, per diems and resource
      person allowance were the most expensive components. Cost of training per person
      per day ranged from I$33 to I$90 when accommodation was required and from I$5 to
      I$21 when training was facility-based. Cost-effectiveness of training was
      assessed in 5 studies with differing measures of effectiveness (knowledge,
      skills, procedure cost and lives saved) making comparison difficult. CONCLUSIONS:
      Economic evaluations of EmOC training are limited. There is a need to scale-up
      and standardise processes that capture both cost and effectiveness of training
      and to agree on suitable economic evaluation models that allow for comparability
      across settings. TRIAL REGISTRATION: PROSPERO_CRD42016041911 .

PMID- 29202732
TI  - Sex differences in response to targeted kyphosis specific exercise and posture
      training in community-dwelling older adults: a randomized controlled trial.
AB  - BACKGROUND: Hyperkyphosis, an excessive anterior curvature in the thoracic spine,
      is associated with reduced health status in older adults. Hyperkyphosis is highly
      prevalent, more common in older women than men. There is no standard intervention
      to reduce age-related hyperkyphosis. Sex differences in response to a kyphosis
      specific exercise intervention are not known. METHODS: We conducted a randomized
      controlled trial of a targeted kyphosis-specific exercise and postural training
      program on the primary outcome Cobb angle of kyphosis, and investigated whether
      the magnitude of change differed between men and women. One hundred twelve
      participants aged >=60 years with kyphosis >=40 degrees  were enrolled and
      randomized to exercise or waitlist control, and 101 participants had analyzable
      baseline and follow-up radiographs for Cobb angle measurements. A group
      intervention including 10 participants per group was delivered by a physical
      therapist, 1-h, twice a week for 3-months. Controls were placed on a waitlist for
      3 months before receiving a delayed intervention. Primary outcome was change from
      baseline to 3-months in Cobb angle measured from standing lateral spine
      radiographs. Secondary outcomes included change over 3-months in kyphometer
      measured kyphosis, physical function and quality of life. Groups were combined
      for analysis after both received the intervention, and sex differences in
      response to the intervention were tested with ANOVA. RESULTS: Participants (60
      women, 41 men) were 70.0 (SD = 5.7) years old with mean Cobb angle 55.9 (SD =
      12.2) degrees at baseline. The active group had higher baseline modified Physical
      Performance Test scores than control, p = 0.03. Men had greater baseline
      kyphometer-measured kyphosis, p = 0.09, and higher bone mineral density (BMD),
      spine strength, more vertebral fractures and diffuse idiopathic skeletal
      hyperostosis (DISH) than women, p <= 0.01. There was no statistically significant
      difference between groups in change in Cobb at 3-months, p = 0.09, however change
      in kyphometer-measured kyphosis differed by 4.8 (95% CI:-6.8,-2.7) degrees, p <
      0.001, favoring the active group. There were no differences between men and women
      in change in either kyphosis measurement after intervention, p > 0.1.
      CONCLUSIONS: A 3-month targeted spine strengthening exercise and posture training
      program reduced kyphometer-measured, but not radiographic-measured kyphosis.
      Despite sex differences in baseline kyphosis, BMD, spine strength, fractures and
      DISH, sex did not affect treatment response. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01766674.

PMID- 29202734
TI  - A tandem CBM25 domain of alpha-amylase from Microbacterium aurum as potential
      tool for targeting proteins to starch granules during starch biosynthesis.
AB  - BACKGROUND: Starch-binding domains from carbohydrate binding module family 20
      have been used as a tool for starch engineering. Previous studies showed that
      expression of starch binding domain fusion proteins in planta resulted in
      modified starch granule structures and physicochemical properties. However,
      although 13 carbohydrate binding module families have been reported to contain
      starch-binding domains, only starch-binding domains from carbohydrate binding
      module family 20 have been well studied and introduced into plants successfully.
      In this study, two fragments, the tandem CBM25 domain and the tandem CBM25 with
      multiple fibronectin type III (FN3) domains of the alpha-amylase enzyme from
      Microbacterium aurum, were expressed in the tubers of a wild type potato cultivar
      (cv. Kardal) and an amylose-free (amf) potato mutant. RESULTS: The (CBM25)2 and
      FN3 protein were successfully accumulated in the starch granules of both Kardal
      and amf transformants. The accumulation of (CBM25)2 protein did not result in
      starch morphological alterations in Kardal but gave rise to rough starch granules
      in amf, while the FN3 resulted in morphological changes of starch granules
      (helical starch granules in Kardal and rough surface granules in amf) but only at
      a very low frequency. The starches of the different transformants did not show
      significant differences in starch size distribution, apparent amylose content,
      and physico-chemical properties in comparison to that of untransformed controls.
      CONCLUSION: These results suggest that the starch-binding domains from
      carbohydrate binding module family 25 can be used as a novel tool for targeting
      proteins to starch granules during starch biosynthesis without side-effects on
      starch morphology, composition and properties.

PMID- 29202733
TI  - Expression of micro-RNAs and genes related to angiogenesis in ccRCC and
      associations with tumor characteristics.
AB  - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the third most common
      urological cancer in adults. Our aim is to evaluate genes and miRNAs expression
      profiles involved with angiogenesis and tumor characteristics in ccRCC. METHODS:
      The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b;
      29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-alpha, VHL,
      PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples
      from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as
      control. The expression levels of miRNAs and genes were related to tumor size,
      Fuhrman nuclear grade and microvascular invasion. RESULTS: miR99a was
      overexpressed in most samples and its target gene mTOR was underexpressed, this
      also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR
      200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression
      was associated with Fuhrman's low grade (p = 0.03). CONCLUSIONS: Our results show
      that in ccRCC there are changes in miRNAs expression affecting gene expression
      that could be important in determining the aggressiveness of this lethal
      neoplasia.

PMID- 29202735
TI  - Use of medical administrative data for the surveillance of psychotic disorders in
      France.
AB  - BACKGROUND: Psychotic disorders are among the most severe psychiatric disorders
      that have great effects on the individuals and the society. For surveillance of
      chronic low prevalence conditions such as psychotic disorders, medical
      administrative databases can be useful due to their large coverage of the
      population, their continuous availability and low costs with possibility of
      linkage between different databases. The aims of this study are to identify the
      population with psychotic disorders by different algorithms based on the French
      medical administrative data and examine the prevalence and characteristics of
      this population in 2014. METHODS: The health insurance system covers the entire
      population living in France and all reimbursements of ambulatory care in private
      practice are included in a national health insurance claim database, which can be
      linked with the national hospital discharge databases. Three algorithms were used
      to select most appropriately persons with psychotic disorders through data from
      hospital discharge databases, reimbursements for psychotropic medication and full
      insurance coverage for chronic and costly conditions. RESULTS: In France in 2014,
      estimates of the number of individuals with psychotic disorders were 469,587
      (54.6% males) including 237,808 with schizophrenia (63.6% males). Of those, 77.0%
      with psychotic disorders and 70.8% with schizophrenia received exclusively
      ambulatory care. Prevalence rates of psychotic disorders were 7.4 per 1000
      inhabitants (8.3 in males and 6.4 in females) and 3.8 per 1000 inhabitants (4.9
      in males and 2.6 in females) for schizophrenia. Prevalence of psychotic disorders
      reached a maximum of 14 per 1000 in males between 35 and 49 years old then
      decreased with age while in females, the highest rate of 10 per 1000 was reached
      at age 50 without decrease with advancing age. No such plateau was observed in
      schizophrenia. DISCUSSION: This study is the first in France using an exhaustive
      sample of medical administrative data to derive prevalence rates for psychotic
      disorders. Although only individuals in contact with healthcare services were
      included, the rates were congruent with reported estimates from systematic
      reviews. The feasibility of this study will allow the implementation of a
      national surveillance of psychotic disorders essential for healthcare management
      and policy planning.

PMID- 29202736
TI  - Peer teacher training (PTT) program for health professional students:
      interprofessional and flipped learning.
AB  - BACKGROUND: The need for developing healthcare professional students' peer
      teaching skills is widely acknowledged, and a number of discipline-based peer
      teacher training programs have been previously reported. However, a consensus on
      what a student peer teaching skills program across the health professions should
      entail, and the associated benefits and challenges, has not been previously
      described. The purpose of this study was to demonstrate the design and
      implementation of an interprofessional Peer Teacher Training (PTT) program, and
      explore outcomes and participant perceptions, using Experience-Based Learning
      (ExBL) theory. METHODS: In 2016, an interprofessional team of academics from
      across three healthcare faculties: Medicine, Pharmacy and Health Sciences,
      developed and implemented a six module, flipped learning, interprofessional PTT
      program. Pre- and post questionnaires, using a Likert scale of 1-5, as well as
      open ended questions, were distributed to students. Descriptive statistics were
      used to analyse quantitative data, and thematic analysis was used to analyse
      qualitative data. RESULTS: Ninety senior students from across the three faculties
      participated. Eighty nine percent of participants completed a pre- and post
      course questionnaire. Students felt the required pre-class preparation, including
      online pre-reading, discussion board, videos, and teaching activities enhanced
      their face-to-face learning experience. In class, students valued the small-group
      activities, and the opportunities to practice their teaching skills with
      provision of feedback. Students reported increased confidence to plan and deliver
      peer teaching activities, and an increased awareness of the roles and
      responsibilities of health professionals outside of their own discipline, and use
      of different terminology and communication methods. Students' suggestions for
      improving the PTT, included; less large group teaching; more online delivery of
      theory; and inclusion of a wider range of health professional disciplines.
      CONCLUSION: The PTT program provided a theoretically informed framework where
      students could develop and practice their teaching skills, helping to shape
      students' professional values as they assume peer teaching responsibilities and
      move towards healthcare practice. The flipped learning, interprofessional format
      was successful in developing students' skills, competence and confidence in
      teaching, assessment, communication and feedback. Importantly, participation
      increased students' awareness and understanding of the various roles of health
      professionals.

PMID- 29202737
TI  - German Beck Scale for Suicide Ideation (BSS): psychometric properties from a
      representative population survey.
AB  - BACKGROUND: Suicidal ideation has been identified as one of the major predictors
      of attempted or actual suicide. Routinely screening individuals for endorsing
      suicidal thoughts could save lives and protect many from severe psychological
      consequences following the suicide of loved ones. The aim of this study was to
      validate the German version of the Beck Scale for Suicide Ideation (BSS) in a
      sample representative for the Federal Republic of Germany. METHODS: All 2450
      participants completed the first part of the Scale, the BSS-Screen. A risk group
      of n = 112 individuals (4.6%) with active or passive suicidal ideation was
      identified and subsequently completed the entire BSS. RESULTS: Satisfactory
      internal reliability (alpha = .97 for the BSS-Screen; alpha = .94 for the entire
      BSS) and excellent model fit indices for the one-dimensional factorial structure
      of the BSS-Screen (CFI = .998; TLI = .995; RMSEA = .045 [95%-CI: .030-.061]) were
      confirmed. Measurement invariance analyses supported strict invariance across
      gender, age, and depression status. We found correlations with related self
      report measures in expected directions comparable to previous studies, indicating
      satisfactory construct validity. LIMITATIONS: Our study involved cross sectional
      data, hence neither predictive validity nor retest-reliability were examined. As
      only the risk group of n = 112 individuals completed the entire measure,
      confirmatory factor analyses could not be conducted for the full BSS. CONCLUSION:
      The German translation of the BSS is a reliable and valid instrument for
      assessing suicidal ideation in the general population. Using it as a screening
      device in general and specialized medical care could substantially advance
      suicide prevention.

PMID- 29202738
TI  - Effects of mistletoe products on pharmacokinetic drug turnover by inhibition and
      induction of cytochrome P450 activities.
AB  - BACKGROUND: European mistletoe (Viscum album) products used in cancer therapy are
      frequently combined with other anti-cancer-drugs. Hence, potential herb-drug
      interactions have become a major safety concern in mistletoe therapy. METHODS:
      Three European mistletoe products (Helixor(r) A, Helixor(r) M and Helixor(r) P
      from mistletoe grown on firs, apple trees and pines, respectively) were tested
      for inhibition of nine major cytochrome P450 (CYP) isoenzymes in a test system
      using pooled human liver microsomes and for induction of five CYP isoforms in
      human hepatocytes cultivated in vitro according to the relevant guideline.
      RESULTS: Major inhibition did not occur in any of the CYP marker reactions. For
      some CYP isoenzymes, a minor or intermediate inhibition could be observed, but
      without dose effect relationship. Induction activity (>= 1.5-fold increase) was
      not found with any of the three mistletoe products. CONCLUSION: Since no
      induction capacity was found and major inhibition above 50% did not occur even
      with the highest concentration used, which is approximately 100,000-fold higher
      than the clinically relevant dose in plasma, a clinically relevant herb-drug
      interaction is not expected for Helixor(r) A, M, and P.

PMID- 29202739
TI  - The lung microbiome in patients with pneumocystosis.
AB  - BACKROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal
      infection that is associated with a high morbidity and mortality in
      immunocompromised individuals. In this study, we analysed the microbiome of the
      lower respiratory tract from critically ill intensive care unit patients with and
      without pneumocystosis. METHODS: Broncho-alveolar fluids from 65 intubated and
      mechanically ventilated intensive care unit patients (34 PCP+ and 31 PCP-
      patients) were collected. Sequence analysis of bacterial 16S rRNA gene V3/V4
      regions was performed to study the composition of the respiratory microbiome
      using the Illumina MiSeq platform. RESULTS: Differences in the microbial
      composition detected between PCP+ and PCP- patients were not statistically
      significant on class, order, family and genus level. In addition, alpha and beta
      diversity metrics did not reveal significant differences between PCP+ and PCP-
      patients. The composition of the lung microbiota was highly variable between PCP+
      patients and comparable in its variety with the microbiota composition of the
      heterogeneous collective of PCP- patients. CONCLUSIONS: The lower respiratory
      tract microbiome in patients with pneumocystosis does not appear to be determined
      by a specific microbial composition or to be dominated by a single bacterial
      species.

PMID- 29202740
TI  - The pleural fluid lactate dehydrogenase/adenosine deaminase ratio differentiates
      between tuberculous and parapneumonic pleural effusions.
AB  - BACKGROUND: Although pleural fluid lactate dehydrogenase (LDH) and adenosine
      deaminase (ADA) levels are often used to distinguish between tuberculous pleural
      effusion (TPE) and parapneumonic pleural effusion (PPE), this can be challenging
      as the LDH level may vary from normal to severely increased in PPE and a
      significantly elevated ADA is frequently measured in both conditions. In this
      study, we evaluated use of the pleural fluid LDH/ADA ratio as a new parameter to
      discriminate TPE from PPE. METHODS: A retrospective study was conducted in
      patients with pathologically-confirmed TPE (n = 72) and PPE (n = 47) to compare
      pleural fluid LDH and ADA levels and LDH/ADA ratios between the 2 groups. A
      receiver operating characteristic (ROC) curve was constructed for identifying
      TPE. RESULTS: The median pleural fluid LDH and ADA levels and LDH/ADA ratios in
      the TPE and PPE groups were: 364.5 U/L vs 4037 U/L (P < .001), 33.5 U/L vs 43.3
      U/L (P = .249), and 10.88 vs 66.91 (P < .0001), respectively. An area under the
      ROC curve of 0.9663 was obtained using the LDH/ADA ratio as the indicator for TPE
      identification, and the sensitivity, specificity, positive likelihood ratio
      (PLR), and negative likelihood ratio (NLR) were, respectively, 93.62%, 93.06%,
      13.48, and 0.068 at a cut-off level of 16.20. CONCLUSIONS: The pleural fluid
      LDH/ADA ratio, which can be determined from routine biochemical analysis, is
      highly predictive of TPE at a cut-off level of 16.20. Measurement of this
      parameter may be helpful for clinicians in distinguishing between TPE and PPE.

PMID- 29202741
TI  - The influence of Osmunda regalis root extract on head and neck cancer cell
      proliferation, invasion and gene expression.
AB  - BACKGROUND: According to only a handful of historical sources, Osmunda regalis,
      the royal fern, has been used already in the middle age as an anti-cancer remedy.
      To examine this ancient cancer cure, an ethanolic extract of the roots was
      prepared and analysed in vitro on its effectiveness against head and neck cancer
      cell lines. METHODS: Proliferation inhibition was measured with the MTT assay.
      Invasion inhibition was tested in a spheroid-based 3-D migration assay on
      different extracellular matrix surfaces. Corresponding changes in gene expression
      were analysed by qRT-PCR array. Induction of apoptosis was measured by
      fluorescence activated cell sorting (FACS) with the Annexin V binding method. The
      plant extract was analysed by preliminary phytochemical tests, liquid
      chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC).
      Anti-angiogenetic activity was determined by the tube formation assay. RESULTS:
      O. regalis extract revealed a growth inhibiting effect on the head and neck
      carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially
      modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less
      sensitive. O. regalis extract inhibited the invasion of cell lines on diverse
      extracellular matrix substrates significantly. Especially the dispersion of the
      highly motile cell line HlaC78 on laminin was almost completely abrogated.
      Motility inhibition on laminin was accompanied by differential gene regulation of
      a variety of genes involved in cell adhesion and metastasis. Furthermore, O.
      regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube
      formation of endothelial cells. Preliminary phytochemical analysis proved the
      presence of tannins, glycosides, steroids and saponins. Liquid
      chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown
      substance with a molecular mass of 864.15 Da, comprising about 50% of the total
      extract. Thin layer chromatography identified ferulic acid to be present in the
      extract. CONCLUSION: The presented results justify the use of royal fern extracts
      as an anti-cancer remedy in history and imply a further analysis of ingredients.

PMID- 29202742
TI  - Milestones-based direct observation tools in internal medicine resident
      continuity clinic.
AB  - BACKGROUND: With milestones-based assessment, there is an increased need for
      tools to facilitate direct observation of clinical trainees. This study was
      designed to compare a Mini-CEX tool to new direct observation tools (DOTs) linked
      to internal medicine milestones. METHODS: A web based survey was used to examine
      satisfaction and usefulness of DOTs compared to the Mini-CEX. Residents and
      preceptors were surveyed three times over 6 months with half serving as control
      (using mini-CEX) compared to those using the DOTs. Likert scale quantitative
      answers and qualitative comments were analyzed using generalized estimating
      equations. RESULTS: Out of 94 residents and 32 faculty 81 and 90% completed the
      survey for at least one time point. In adjusted models, there was no significant
      change in resident evaluation comparing the tools on a number of questions
      including overall satisfaction and resident perception of receiving high quality
      feedback. By contrast, faculty preceptors reported increased ratings on many of
      the questions evaluating their use of the new tools including ability to provide
      higher quality feedback and overall satisfaction. A number of challenges and
      benefits of the new tools were identified in qualitative feedback by both
      residents and preceptors. CONCLUSIONS: All parties recognized the value and
      limitations of direct observation. Overall these new office based DOTs were
      perceived similarly to the mini-CEX by residents while faculty reported higher
      satisfaction. The DOTs are a useful addition to the tool box available for the
      assessment of clinical skills of medical trainees, especially from the viewpoint
      of faculty preceptors.

PMID- 29202743
TI  - Posterior intervertebral space debridement, annular bone grafting and
      instrumentation for treatment of lumbosacral tuberculosis.
AB  - BACKGROUND: The choice of surgical methods for lumbosacral tuberculosis is
      controversial due to the complex anterior anatomy and peculiar biomechanics of
      the lumbosacral junction. The objective of this study was to explore the clinical
      effect of posterior intervertebral space debridement with annular bone graft
      fusion and fixation for the treatment of lumbosacral tuberculosis. METHODS: We
      retrospectively analysed data from 23 patients with lumbosacral tuberculosis who
      had undergone posterior intervertebral space debridement with annular bone fusion
      and fixation between January 2008 and September 2014. The mean age of the
      patients was 49.0 years (range, 27-71), and the mean duration of disease until
      treatment was 10.2 months (range, 6-20). The lumbosacral angle, visual analogue
      scale (VAS) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
      level, American Spinal Injury Association (ASIA) grade and Social Functioning-36
      (SF-36) score were determined to ascertain the clinical effects of the treatment.
      RESULTS: All patients underwent follow-up observation. The mean follow-up time
      was 34.2 months (range, 18-45), the mean operation time was 167.0 min (range, 130
      210) and the mean blood loss was 767.4 ml (range, 500-1150). The lumbosacral
      angle was 21.0 degrees  +/- 2.1 degrees  before operation, rising to 28.8 degrees
      +/- 1.7 degrees  after operation (p < 0.05) and being maintained thereafter. The
      mean VAS score before operation was 8.1 +/- 0.6, decreasing to 1.2 +/- 0.5 (p <
      0.05) at the final follow-up. The mean ESR and CRP values were 49.1 +/- 5.6 mm
      and 64.9 +/- 11.9 mg/L, respectively, before operation, decreasing to normal at
      the final follow-up. The preoperative ASIA grade was C in 6 patients, D in 12 and
      E in 5. At the final follow-up, all patients had an ASIA grade of E except for
      one patient with a grade of D. For all patients, the SF-36 score at the final
      follow-up was higher than the preoperative and postoperative scores. CONCLUSIONS:
      Posterior intervertebral space debridement with annular bone graft fusion and
      fixation is an effective treatment for lumbosacral spine tuberculosis.

PMID- 29202745
TI  - The association of N-terminal pro-brain-type natriuretic peptide with
      hemodynamics and functional capacity in therapy-naive precapillary pulmonary
      hypertension: results from a cohort study.
AB  - BACKGROUND: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is
      currently used as a surrogate marker for disease severity in pulmonary
      hypertension (PH). However, NT-proBNP tends to have a high variability and may
      insufficiently correlate with hemodynamics and exercise capacity. METHODS: To
      investigate the association of NT-proBNP with hemodynamics and cardio-pulmonary
      exercise testing (CPET) in 84 therapy-naive patients with precapillary PH.
      RESULTS: NT-proBNP levels were significantly correlated with hemodynamics and
      CPET parameters except for cardiac index, diffusion capacity, PaO2 at peak
      exercise, and peak minute ventilation. NT-proBNP correlated best with
      hemodynamics and CPET in women and patients >65 years. NT-proBNP correlated
      better with CPET in pulmonary arterial hypertension compared to chronic
      thromboembolic PH (CTEPH). CONCLUSION: NT-proBNP is associated with disease
      severity in precapillary PH. The association might be age- and gender-dependent.
      NT-proBNP may insufficiently correlate with disease severity in CTEPH, possibly
      due to comorbidity.

PMID- 29202744
TI  - Biomarkers of collagen turnover are related to annual change in FEV1 in patients
      with chronic obstructive pulmonary disease within the ECLIPSE study.
AB  - BACKGROUND: Change in forced expiratory volume in one second (FEV1) is important
      for defining severity of chronic obstructive pulmonary disease (COPD).
      Serological neoepitope markers of collagen turnover may predict rate of change in
      FEV1. METHODS: One thousand COPD subjects from the observational, multicentre,
      three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive
      Surrogate Endpoints) study (NCT00292552, trial registration in February 2006)
      were included. Matrix metalloproteinase (MMP)-generated fragments of collagen
      type I, and type VI (C1M and C6M) were assessed in month six serum samples. A
      random-coefficient model with both a random intercept and a random slope was used
      to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD
      FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator
      reversibility, prior exacerbations, emphysema and chronic bronchitis status at
      baseline. RESULTS: Annual change of PD-FEV1 was estimated from a linear model for
      the two-year study period. Serum C1M and C6M were independent predictors of lung
      function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma
      hsCRP and emphysema were also significant predictors. The effect estimate between
      annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M
      was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with
      baseline FEV1. CONCLUSION: We demonstrated that markers of tissue turnover were
      significantly associated with lung function change. These markers may function as
      prognostic biomarkers and possibly as efficacy biomarkers in clinical trials
      focusing on lung function change in COPD. TRIAL REGISTRATION: NCT00292552 ,
      Retrospectively registered, trial registration in February 2006.

PMID- 29202747
TI  - Seroprevalence of toxoplasmosis and risk factors of Toxoplasma gondii infection
      among pregnant women in Sri Lanka: a cross sectional study.
AB  - BACKGROUND: Toxoplasma gondii is an intracellular protozoan infecting humans and
      animals. Infection in adults usually causes mild disease but greater importance
      lies in preventing transplacental transmission which can cause major foetal
      anomalies and is vital to identify infection in pregnancy. Research on this
      regard in Sri Lanka is scarce and would be beneficial in developing antenatal
      care strategies for improved foetal outcome. METHODS: A random sample of 536
      pregnant women attending antenatal care in Teaching Hospital Peradeniya from 2010
      to 2013 was recruited for this study. Blood samples were tested for Toxoplasma
      gondii IgG and IgM antibodies from the participants by using a commercial ELISA
      kit with a cut-off OD value of >1 and a structured questionnaire was used to
      identify the exposure to risk. Bivariate analysis using the Chi Square test was
      used to calculate associations between documented risk factors and seropositivity
      and a p value of <0.05 was taken as significant. RESULTS: Among the participants
      160 (29.9%) were positive for T. gondii IgG antibodies and 2 (0.37%) were IgM
      positive. The seroprevalence in the first, second and third trimesters were
      30.4%, 30.6% and 26.1% respectively. Of the risk factors studied, preparation and
      selling raw meat (p = 0.05) and household gardening (p = 0.01) were significant
      whereas the presence of domesticated cats and dogs, eating locally produced meat
      or dairy products did not show significant associations. CONCLUSIONS:
      Seroprevalence of T. gondii present among pregnant women attending antenatal care
      in Peradeniya was 29.9% indicating high level of transmission among the study
      population. However 70.1% of the study population were seronegative and were
      susceptible to primary acute infection during pregnancy and possible foetal
      anomalies. Therefore implementing health education especially on the
      aforementioned risk factors is recommended.

PMID- 29202746
TI  - Translation of the humeral head scale is associated with success of rotator cuff
      repair for large-massive tears.
AB  - BACKGROUND: Although a loss of rotator cuff integrity leads to the superior
      migration of the humeral head, the parameters that characterize the anterolateral
      migration of the humeral head have not been established. The purpose of this
      study was to investigate the correlation between the translation of the humeral
      head scale (T-scale) and clinical outcomes of rotator cuff repair, as well as the
      correlation between the T-scale and radiologic parameters. METHODS: One hundred
      thirty-five consecutive patients with full-thickness rotator cuff tears underwent
      primary rotator cuff repair. The T-scale, which indicates the distance from the
      center of the humeral head to the lateral coracoacromial arch, was measured on
      axial computed tomography scans, and the acromiohumeral interval (AHI) was
      measured radiographically. The correlation of the two parameters with the
      clinical scores of the Japanese Orthopaedic Association and University of
      California-Los Angeles scores and active forward elevation (FE) were evaluated at
      the preoperative and postoperative stages, respectively. RESULTS: The
      postoperative T-scale and AHI correlated well with the postoperative FE and
      clinical scores in the patients with large-massive tears but not in those
      patients with small-medium tears and preoperative large-massive tears. A
      significant correlation was observed between the postoperative T-scale and AHI.
      The T-scale was subject to cuff repair integrity. CONCLUSIONS: We demonstrated
      that the postoperative T-scale was well correlated with the clinical results and
      postoperative AHI after rotator cuff repair for large-massive tears, indicating
      that poor outcomes are associated with combined superior and anterolateral
      migration of the humeral head following retears.

PMID- 29202748
TI  - Two occurrences of delayed epidural hematoma in different areas following
      decompressive craniectomy for acute subdural hematoma in a single patient: a case
      report.
AB  - BACKGROUND: Delayed epidural hematoma (DEH) following evacuation of traumatic
      acute subdural hematoma (ASDH) or acute epidural hematoma (EDH) is a rare but
      devastating complication, especially when it occurs sequentially in a single
      patient. CASE PRESENTATION: A 19-year-old man who developed contralateral DEH
      following craniotomy for evacuation of a traumatic right-side ASDH and then
      developed a left-side DEH of the posterior cranial fossa after craniotomy for
      evacuation of the contralateral DEH. He was immediately returned to the operating
      room for additional surgeries and his neurological outcome was satisfactory.
      CONCLUSIONS: Although DEH occurring after evacuation of ASDH or acute EDH is a
      rare event, timely recognition is critical to prognosis.

PMID- 29202749
TI  - Inhibitory or excitatory? Optogenetic interrogation of the functional roles of
      GABAergic interneurons in epileptogenesis.
AB  - Alteration in the excitatory/inhibitory neuronal balance is believed to be the
      underlying mechanism of epileptogenesis. Based on this theory, GABAergic
      interneurons are regarded as the primary inhibitory neurons, whose failure of
      action permits hyperactivity in the epileptic circuitry. As a consequence,
      optogenetic excitation of GABAergic interneurons is widely used for seizure
      suppression. However, recent evidence argues for the context-dependent, possibly
      "excitatory" roles that GABAergic cells play in epileptic circuitry. We reviewed
      current optogenetic approaches that target the "inhibitory" roles of GABAergic
      interneurons for seizure control. We also reviewed interesting evidence that
      supports the "excitatory" roles of GABAergic interneurons in epileptogenesis.
      GABAergic interneurons can provide excitatory effects to the epileptic circuits
      via several distinct neurological mechanisms. (1) GABAergic interneurons can
      excite postsynaptic neurons, due to the raised reversal potential of GABA
      receptors in the postsynaptic cells. (2) Continuous activity in GABAergic
      interneurons could lead to transient GABA depletion, which prevents their
      inhibitory effect on pyramidal cells. (3) GABAergic interneurons can synchronize
      network activity during seizure. (4) Some GABAergic interneurons inhibit other
      interneurons, causing disinhibition of pyramidal neurons and network
      hyperexcitability. The dynamic, context-dependent role that GABAergic
      interneurons play in seizure requires further investigation of their functions at
      single cell and circuitry level. New optogenetic protocols that target GABAergic
      inhibition should be explored for seizure suppression.

PMID- 29202750
TI  - Assessment of tetralogy of Fallot-associated congenital extracardiac vascular
      anomalies in pediatric patients using low-dose dual-source computed tomography.
AB  - BACKGROUND: To investigate the diagnostic value of dual-source computed
      tomography (DSCT) in the evaluation of tetralogy of Fallot (TOF)-associated
      extracardiac vascular abnormalities in pediatric patients compared with
      transthoracic echocardiography (TTE). METHODS: One hundred and twenty-three
      pediatric patients diagnosed with TOF were included in this retrospective study.
      All patients underwent DSCT and TTE preoperatively. All associated extracardiac
      vascular abnormalities and their percentages were recorded. The diagnostic
      performances of DSCT and TTE were compared based on the surgical results. The
      image quality of DSCT was rated, and the effective radiation dose (ED) was
      calculated. RESULTS: A total of 159 associated extracardiac vascular deformities
      were confirmed by surgery. Patent ductus arteriosus (36, 22.64%), right-sided
      aortic arch (29, 18.24%), and pulmonary valve stenosis (23, 14.47%) were the most
      common associated extracardiac vascular abnormalities. DSCT was superior to TTE
      in demonstrating associated extracardiac anomalies (diagnostic accuracy: 99.13%
      vs. 97.39%; sensitivity: 92.45% vs. 77.07%; specificity: 99.81% vs. 99.42%). The
      agreement on grading the image quality of DSCT was excellent (kappa = 0.80), and
      the mean score of the image quality was 3.39 +/- 0.50. The mean ED of DSCT was
      0.86 +/- 0.47 mSv. CONCLUSIONS: Compared to TTE, low-dose DSCT has high
      diagnostic accuracy in the depiction of associated extracardiac vascular
      anomalies in pediatric patients with TOF, and could provide more morphological
      details for surgeons.

PMID- 29202751
TI  - Walnut consumption in a weight reduction intervention: effects on body weight,
      biological measures, blood pressure and satiety.
AB  - BACKGROUND: Dietary strategies that help patients adhere to a weight reduction
      diet may increase the likelihood of weight loss maintenance and improved long
      term health outcomes. Regular nut consumption has been associated with better
      weight management and less adiposity. The objective of this study was to compare
      the effects of a walnut-enriched reduced-energy diet to a standard reduced-energy
      density diet on weight, cardiovascular disease risk factors, and satiety.
      METHODS: Overweight and obese men and women (n = 100) were randomly assigned to a
      standard reduced-energy-density diet or a walnut-enriched (15% of energy) reduced
      energy diet in the context of a behavioral weight loss intervention. Measurements
      were obtained at baseline and 3- and 6-month clinic visits. Participants rated
      hunger, fullness and anticipated prospective consumption at 3 time points during
      the intervention. Body measurements, blood pressure, physical activity, lipids,
      tocopherols and fatty acids were analyzed using repeated measures mixed models.
      RESULTS: Both study groups reduced body weight, body mass index and waist
      circumference (time effect p < 0.001 for each). Change in weight was -9.4 (0.9)%
      vs. -8.9 (0.7)% (mean [SE]), for the standard vs. walnut-enriched diet groups,
      respectively. Systolic blood pressure decreased in both groups at 3 months, but
      only the walnut-enriched diet group maintained a lower systolic blood pressure at
      6 months. The walnut-enriched diet group, but not the standard reduced-energy
      density diet group, reduced total cholesterol and low-density lipoprotein
      cholesterol (LDL-C) at 6 months, from 203 to 194 mg/dL and 121 to 112 mg/dL,
      respectively (p < 0.05). Self-reported satiety was similar in the groups.
      CONCLUSIONS: These findings provide further evidence that a walnut-enriched
      reduced-energy diet can promote weight loss that is comparable to a standard
      reduced-energy-density diet in the context of a behavioral weight loss
      intervention. Although weight loss in response to both dietary strategies was
      associated with improvements in cardiovascular disease risk factors, the walnut
      enriched diet promoted more favorable effects on LDL-C and systolic blood
      pressure. TRIAL REGISTRATION: The trial is registered at ( NCT02501889 ).

PMID- 29202752
TI  - Correction to: Integrative analysis associates monocytes with insufficient
      erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques.
AB  - After publication of the article [1], it was brought to our attention that
      several symbols were missing from Fig. 1, including some cited in the figure's
      key. The correct version of the figure is shown below and has now been updated in
      the original article.

PMID- 29202753
TI  - Development of triptolide-nanoemulsion gels for percutaneous administration:
      physicochemical, transport, pharmacokinetic and pharmacodynamic characteristics.
AB  - BACKGROUND: This work aimed to provide useful information on the use of
      nanoemulsions for the percutaneous administration of triptolide. Lipid
      nanosystems have great potential for transdermal drug delivery. Nanoemulsions and
      nanoemulsion gels were prepared to enhance percutaneous permeation.
      Microstructure and in vitro/in vivo percutaneous delivery characteristics of
      triptolide (TPL)-nanoemulsions and TPL-nanoemulsion gels were compared. The
      integrity of the nanoemulsions and nanoemulsion gels during transdermal delivery
      and its effects on the surface of skin were also investigated. The penetration
      mechanisms of nanoemulsions and nanoemulsion gels were investigated by
      differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (FTIR). The transport characteristics of fluorescence-labelled
      nanoemulsions were probed using laser scanning confocal microscopy. A chronic
      dermatitis/eczema model in mice ears and the pharmacodynamic of the TPL
      nanoemulsion gels were also investigated. RESULTS: Compared to TPL gels,
      significantly greater cumulative amounts of TPL-nanoemulsion gels and TPL
      nanoemulsions penetrated rat skin in vitro. The in vivo microdialysis showed the
      concentration-time curve AUC0-t for TPL-NPs is bigger than the TPL-gels. At the
      same time, TPL-NPs had a larger effect on the surface of skin. By hydrating
      keratin and changing the structure of both the stratum corneum lipids and
      keratin, nanoemulsions and nanoemulsion gels influence skin to promote
      percutaneous drug penetration. Both hairfollicles and the stratum corneum are
      also important in this transdermal drug delivery system. Moderate and high
      dosages of the TPL-nanoemulsion gels can significantly improve the symptoms of
      dermatitis/eczema inflammation and edema erythematic in mice ears and can reduce
      the expression of IFN-gamma and IL-4. Moreover, the TPL-nanoemulsion gels cause
      less gastrointestinal damage than that of the Tripterygium wilfordii oral tablet
      does. CONCLUSIONS: Nanoemulsions could be suitable for transdermal stably
      releasing drugs and maintaining the effective drug concentration. The TPL
      nanoemulsion gels provided higher percutaneous amounts than other carriers did.
      These findings suggest that nanoemulsion gels could be promising percutaneous
      carriers for TPL. The TPL-nanoemulsion gels have a significant treatment effect
      on dermatitis/eczema in the mice model and is expected to provide a new, low
      toxicity and long-term preparation for the clinical treatment of
      dermatitis/eczema in transdermal drug delivery systems.

PMID- 29202754
TI  - Institutional context and VCT practitioner narratives: possibilities and
      limitations for HIV prevention in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Voluntary Counseling and Testing (VCT) is an HIV prevention strategy
      that promotes the principles of confidentiality and informed consent.
      International research has highlighted VCT counselors' isolation from service
      planning and the contradictions they negotiate between local values and global
      testing recommendations. In Brazil, studies have identified many limitations,
      including counselors' difficulties to implement a vulnerability approach to HIV
      prevention as recommended in the country's national guidelines. These studies,
      however, have not considered the particularities of the institutional contexts
      where counselors work. This research addresses these gaps in the VCT literature
      by exploring how VCT services are organized and how counselors perceive and
      perform their practices in the state of Rio de Janeiro, Brazil. METHODS: This is
      a case study of VCT services in the state of Rio de Janeiro. The research design
      included individual structured interviews with seven VCT service coordinators and
      twenty individual semi-structured interviews with VCT counselors. Participants
      were sampled according to gender, undergraduate degree and work trajectory to
      capture a diverse range counselor narratives. RESULTS: The VCT services were
      relatively homogenous in terms of functioning and had a similar restricted roll
      of activities including individual counseling and occasional external prevention
      activities with groups vulnerable to HIV. All VCT services reported reductions in
      staff size. Some counselors used dialogical practices to build trust, guarantee
      confidentiality and adjust their practices in accordance with their clients'
      values and practices. Others emphasized imperative messages or focused on risk
      and individual responsibility. Connections between how counselors perceive their
      practices and the organization of their work environment were observed.
      CONCLUSIONS: Due to the importance of counseling as a prevention strategy we
      recommend rethinking the relationship between counselors' practices and the
      organization of VCT services. The challenges brought about by the expansion of
      "test and treat" programs globally and other social and symbolic aspects of the
      HIV epidemic, such as gender inequalities, must also be taken into account.
      Further reflection is also needed on the relationship between counseling
      guidelines and practices within the vulnerability approach to HIV prevention.

PMID- 29202755
TI  - H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada
      syndrome by modulating DNA methylation of SCN5A promoters.
AB  - BACKGROUND: A common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves
      sodium channel activity in mutated channels and known to be a genetic modifier of
      Brugada syndrome patients (BrS). We investigated clinical manifestations and
      underlying mechanisms of H558R in BrS. METHODS AND RESULTS: We genotyped H558R in
      100 BrS (mean age 45 +/- 14 years; 91 men) and 1875 controls (mean age 54 +/- 18
      years; 1546 men). We compared clinical parameters in BrS with and without H558R
      (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections
      from 30 patients during aortic aneurysm operations and compared SCN5A expression
      and methylation with or without H558R. H558R was less frequent in BrS than
      controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly
      lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in
      H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level
      was significantly higher and the methylation rate was significantly lower in
      sections with H558R (N = 10) than those without (0.98 +/- 0.14 vs. 0.83 +/- 0.19,
      P = 0.04; 0.7 +/- 0.2% vs. 1.6 +/- 0.1%, P = 0.004, respectively). In BrS with
      heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G
      allele expression. CONCLUSION: The SCN5A polymorphism H558R may be a modifier
      that protects against VF occurrence in BrS. The H558R decreased the SCN5A
      promoter methylation and increased the expression level in cardiac tissue. An
      allelic expression imbalance in BrS with a heterozygous H558R may also contribute
      to the protective effects in heterozygous mutations.

PMID- 29202756
TI  - Pestivirus infection in cattle dairy farms: E2 glycoprotein ELISA reveals the
      presence of bovine viral diarrhea virus type 2 in northwestern Italy.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) types 1 and 2 are members of the
      Pestivirus genus of the Flaviviridae family. This genus also includes the HoBi
      like virus, tentatively classified as BVDV type 3. BVDV-1 is widely distributed
      in Italy despite the extensive use of BVDV-1-based vaccines, while BVDV-2 and
      HoBi-like Pestivirus have been detected occasionally. Monitoring the occurrence
      of sporadic or atypical pestiviruses is a useful approach to evaluate the need
      for additional vaccine strains that can be used in BVDV control programs.
      RESULTS: In this study we developed a multiwell antibody ELISA based on the
      recombinant E2 protein of the three bovine pestiviruses. We evaluated the assay's
      applicability for surveillance purposes using pooled milk samples, each prepared
      from a maximum of 35 lactating cows and collected from 176 dairy herds. As
      expected, the majority of the pooled samples reacted to a greater extent against
      the BVDV-1 E2 antigen. All three milk pools from a single farm reacted to the
      BVDV-2 antigen, however. Further analysis using spot tests, antigen detection,
      and sequence analysis of the 5'-UTR region confirmed the presence of five
      persistently infected calves carrying a BVDV-2a strain. CONCLUSIONS: This study
      highlights for the first time that sporadic circulation of BVDV-2 can be
      predicted by immunoenzymatic methods in the absence of specific vaccination.

PMID- 29202757
TI  - Spatially balanced provision of health equipment: a cross-sectional study
      oriented to the identification of challenges to access promotion.
AB  - BACKGROUND: Access to health services is in part defined by the spatial
      distribution of healthcare equipment. To ensure equity in the provision of health
      services, it is important to examine availability across different health care
      providers taking into account population demand. Given the importance of the
      equitable provision of health equipment, we evaluate its spatial distribution in
      Brazil. METHODS: This study is classified as cross-sectional with an ecological
      design. We evaluate Brazilian data on distance to available health equipment
      considering: dialysis machines (385), magnetic resonance imaging (MRI) (257),
      hospital beds (3675) and bone densitometers (429). We define two distance
      thresholds (50 km and 200 km) from a municipality to the center of services
      provision. The balance between infrastructure capacity and potential demand was
      evaluated to identify a lack or surplus of health services. RESULTS: The
      distribution of dialysis equipment and bone densitometers is not balanced across
      Brazilian states, and unmet demand is high. With respect to MRIs, the large
      capacity of this equipment results in a large excess of supply. However, this
      characteristic alone cannot account for excesses of supply of over 700%, as is
      the case of the Federal District when the range is limited to 50 km. At the same
      time, four states in the Northeastern region of Brazil show a net excess of
      demand. Some regions do not meet the standard amount of supply defined by
      Brazilian Ministry of Health. The quantity and distribution of hospital beds are
      not sufficient to provide full coverage to the population. CONCLUSION: Our main
      focus was to evaluate the network of the provision of health equipment in Brazil,
      considering both private and public sectors conjointly. We take into account two
      main aspects of a spatially balanced health system: the regional availability of
      health equipment and the geographic distance between its demand and supply at the
      municipality level. Some regions do not meet the minimum requirement defined by
      the Brazilian Ministry of Health regarding the supply of health services.

PMID- 29202758
TI  - Health related quality of life among myocardial infarction survivors in the
      United States: a propensity score matched analysis.
AB  - BACKGROUND: Little is known regarding the health-related quality of life among
      myocardial infarction (MI) survivors in the United States. The purpose of this
      population-based study was to identify differences in health-related quality of
      life domains between MI survivors and propensity score matched controls. METHODS:
      This retrospective, cross-sectional matched case-control study examined
      differences in health-related quality of life (HRQoL) among MI survivors of
      myocardial infarction compared to propensity score matched controls using data
      from the 2015 Behavioral Risk Factor Surveillance System (BRFSS) survey.
      Propensity scores were generated via logistic regression for MI survivors and
      controls based on gender, race/ethnicity, age, body mass index (BMI), smoking
      status, and comorbidities. Chi-square tests were used to compare differences
      between MI survivors to controls for demographic variables. A multivariate
      analysis of HRQoL domains estimated odds ratios. Life satisfaction, sleep
      quality, and activity limitations were estimated using binary logistic
      regression. Social support, perceived general health, perceived physical health,
      and perceived mental health were estimated using multinomial logistic regression.
      Significance was set at p < 0.05. RESULTS: The final sample consisted of 16,729
      MI survivors matched to 50,187 controls (n = 66,916). Survivors were
      approximately 2.7 times more likely to report fair/poor general health compared
      to control (AOR = 2.72, 95% CI: 2.43-3.05) and 1.5 times more likely to report
      limitations to daily activities (AOR = 1.46, 95% CI: 1.34-1.59). Survivors were
      more likely to report poor physical health >15 days in the month (AOR = 1.63, 95%
      CI: 1.46-1.83) and poor mental health >15 days in the month (AOR = 1.25, 95% CI:
      1.07-1.46) compared to matched controls. There was no difference in survivors
      compared to controls in level of emotional support (rarely/never: AOR = 0.75, 95%
      CI: 0.48-1.18; sometimes: AOR = 0.73, 95% CI: 0.41-1.28), hours of recommended
      sleep (AOR = 1.14, 95% CI: 0.94-1.38), or life satisfaction (AOR = 1.62, 95% CI:
      0.99-2.63). CONCLUSION: MI survivors experienced lower HRQoL on domains of
      general health, physical health, daily activity, and mental health compared to
      the general population.

PMID- 29202759
TI  - Effects of intramuscularly administered enrofloxacin on the susceptibility of
      commensal intestinal Escherichia coli in pigs (sus scrofa domestica).
AB  - BACKGROUND: In the European Union, various fluoroquinolones are authorised for
      the treatment of food producing animals. Each administration poses an increased
      risk of development and spread of antimicrobial resistance. The aim of this study
      was to investigate the impact of parenteral administration of enrofloxacin on the
      prevalence of enrofloxacin and ciprofloxacin susceptibilities in the commensal
      intestinal E. coli population. METHODS: E. coli isolates from faeces of twelve
      healthy pigs were included. Six pigs were administered enrofloxacin on day 1 to 3
      and after two weeks for further three days. The other pigs formed the control
      group. MIC values were determined. Virulence and resistance genes were detected
      by PCR. Phylogenetic grouping was performed by PCR. Enrofloxacin and
      ciprofloxacin were analysed in sedimentation samples by HPLC. RESULTS:
      Susceptibility shifts in commensal E. coli isolates were determined in both
      groups. Non-wildtype E. coli could be cultivated from two animals of the
      experimental group for the first time one week after the first administration and
      from one animal of the control group on day 28. The environmental load with
      enrofloxacin in sedimentation samples showed the highest amount between days one
      and five. The repeated parenteral administration of enrofloxacin to pigs resulted
      in rapidly increased MIC values (day 28: MIC up to 4 mg/L, day 35: MIC >=
      32mg/L). E. coli populations of the control group in the same stable without
      direct contact to the experimental group were affected. CONCLUSION: The
      parenteral administration of enrofloxacin to piglets considerably reduced the
      number of the susceptible intestinal E. coli population which was replaced by E.
      coli strains with increased MIC values against enrofloxacin. Subsequently also
      pigs of the control were affected suggesting a transferability of strains from
      the experimental group through the environment to the control group especially as
      we could isolate the same PFGE strains from both pig groups and the environment.

PMID- 29202760
TI  - Injections frequency and health care costs in patients treated with aflibercept
      compared to ranibizumab: new real-life evidence from Switzerland.
AB  - BACKGROUND: Previous analyses of real-life data indicated that injection
      frequency and health care costs did not differ for anti-VEGF treatment with
      aflibercept and ranibizumab. The objective of this study was to investigate
      whether this finding persisted when analysing a longer time period after
      licensing. METHODS: Retrospective analysis of health insurance claims data of two
      large Swiss basic health insurance plans including 28% of the Swiss population.
      Patients qualified for inclusion if aflibercept or ranibizumab treatment had been
      initiated between June 1, 2013 and November 1, 2014. Within this set, patients
      with at least 12 months of continuous insurance enrolment in the previous year,
      12-month follow-up, and without change of anti-VEGF drug were considered. We
      examined the distribution of demographic data and patient characteristics between
      those receiving ranibizumab and those receiving aflibercept. Numbers of
      injections and associated health care expenditures observed during the 12-month
      follow-up period after incident treatment were the two outcomes considered. In
      multivariate regression analyses, controlling for possible confounding factors,
      we compared differences in these two outcomes between patients treated with
      aflibercept as compared to ranibizumab. RESULTS: A total of 3'058 patients were
      analysed, 790 (26%) receiving aflibercept and 2'268 receiving ranibizumab (74%).
      The use of aflibercept (average number of injections 6.2) as compared to
      ranibizumab (average number of injections 5.7) in the follow-up period of 1 to 12
      months, was associated with a 12% increase in the injection frequency (95%
      confidence interval (CI) 6-17%; p < 0.001). CONCLUSIONS: Real-life data
      contradicts the assumption that aflibercept is used less frequently as compared
      to ranibizumab. This results in similar total health care expenditures for both
      anti-VEGF agents.

PMID- 29202761
TI  - Hilbert-Schmidt and Sobol sensitivity indices for static and time series Wnt
      signaling measurements in colorectal cancer - part A.
AB  - BACKGROUND: Ever since the accidental discovery of Wingless [Sharma R.P.,
      Drosophila information service, 1973, 50, p 134], research in the field of Wnt
      signaling pathway has taken significant strides in wet lab experiments and
      various cancer clinical trials, augmented by recent developments in advanced
      computational modeling of the pathway. Information rich gene expression profiles
      reveal various aspects of the signaling pathway and help in studying different
      issues simultaneously. Hitherto, not many computational studies exist which
      incorporate the simultaneous study of these issues. RESULTS: This manuscript ?
      explores the strength of contributing factors in the signaling pathway, ?
      analyzes the existing causal relations among the inter/extracellular factors
      effecting the pathway based on prior biological knowledge and ? investigates the
      deviations in fold changes in the recently found prevalence of psychophysical
      laws working in the pathway. To achieve this goal, local and global sensitivity
      analysis is conducted on the (non)linear responses between the factors obtained
      from static and time series expression profiles using the density (Hilbert
      Schmidt Information Criterion) and variance (Sobol) based sensitivity indices.
      CONCLUSION: The results show the advantage of using density based indices over
      variance based indices mainly due to the former's employment of distance measures
      & the kernel trick via Reproducing kernel Hilbert space (RKHS) that capture
      nonlinear relations among various intra/extracellular factors of the pathway in a
      higher dimensional space. In time series data, using these indices it is now
      possible to observe where in time, which factors get influenced & contribute to
      the pathway, as changes in concentration of the other factors are made. This
      synergy of prior biological knowledge, sensitivity analysis & representations in
      higher dimensional spaces can facilitate in time based administration of target
      therapeutic drugs & reveal hidden biological information within colorectal cancer
      samples.

PMID- 29202763
TI  - Classification and sensitivity analysis of the transmission dynamic of hepatitis
      B.
AB  - BACKGROUND: Hepatitis B infection caused by the hepatitis B virus is one of the
      most serious viral infections and a global health problem. In the transmission of
      hepatitis B infection, three different phases, i.e. acute infected, chronically
      infected, and carrier individuals, play important roles. Carrier individuals are
      especially significant, because they do not exhibit any symptoms and are able to
      transmit the infection. Here we assessed the transmissibility associated with
      different infection stages of hepatitis B and generated an epidemic model.
      METHODS: To demonstrate the transmission dynamic of hepatitis B, we investigate
      an epidemic model by dividing the infectious class into three subclasses, namely
      acute infected, chronically infected, and carrier individuals with both
      horizontal and vertical transmission. RESULTS: Numerical results and sensitivity
      analysis of some important parameters are presented to show that the proportion
      of births without successful vaccination, perinatally infected individuals, and
      direct contact rate are highest risk factors for the spread of hepatitis B in the
      community. CONCLUSION: Our work provides a coherent platform for studying the
      full dynamics of hepatitis B and an effective direction for theoretical work.

PMID- 29202764
TI  - Influence of different sample preparation strategies on the proteomic
      identification of stress biomarkers in porcine saliva.
AB  - BACKGROUND: The influence of two different sample treatments comprising the
      enrichment of glycoproteins by boronic acid and dynamic range compression by
      hexapeptide libraries, on the detection of stress markers in saliva of pigs was
      evaluated in this study. For this purpose, saliva samples collected before and
      after the application of an acute stress model consisting of nasal restraining in
      pigs were processed without any treatment and with the two different treatments
      mentioned above. Protein separation by two-dimensional gel electrophoresis (2-DE)
      followed by identification of proteins using MALDI-TOF/TOF mass spectrometry (MS)
      was used as proteomic technique. RESULTS: The application of each of the two
      different sample treatment protocols allowed the identification of unique
      proteins that could be potential salivary acute stress markers in pigs: lipocalin
      1, protein S100-A8 and immunoglobulin M by enrichment of glycoproteins; protein
      S100-A9, double headed protease inhibitor submandibular gland, and haemoglobin by
      dynamic range compression; and protein S100-A12 by both protocols. Salivary
      lipocalin, prolactin inducible protein, light chain of immunoglobulins, adenosine
      deaminase and carbonic anhydrase VI were identified as potential markers in
      untreated saliva as well as one of the other treatments. CONCLUSION: The use of
      different procedures allowed the detection of different potential stress markers.
      Although from a practical point of view, the use of saliva without further
      treatment as well as the enrichment of glycoproteins are less expensive and easy
      to do procedures.

PMID- 29202765
TI  - A novel technique for modified all-inside repair of bucket-handle meniscus tears
      using standard arthroscopic portals.
AB  - BACKGROUND: Bucket-handle meniscus tears (BHMT) are often displaced and unstable.
      The inside-out technique of repairing such tears is currently the gold standard.
      All-inside repair with meniscal fixators is getting increasingly popular.
      Shortcomings of the inside-out technique include neurovascular complications,
      especially saphenous nerve palsy, and retention of a non-resorbable suture which
      can result in discomfort to patient, granuloma formation, and a foci of
      infection. Hence, the purpose of this project was to innovate a novel all-inside
      technique to precisely reduce and fix BHMT while avoiding neurovascular
      complications and retention of a non-resorbable suture. METHODS: Routine
      arthroscopic portals were created on a patient's left knee with a displaced BHMT.
      Through the anteromedial portal, a conjoint pseudo double lumen cannula was
      inserted. Two limbs of a reduction suture were passed through the cannula, one
      over the "femoral" surface of the meniscus, one over the "tibial" surface of the
      meniscus anterior to the biceps femoris tendon, with the knee flexed at 20
      degrees  to avoid injury to the saphenous nerve. Suture limbs were passed out
      percutaneously and tensioned. RESULTS: Anatomic reduction was ensured under
      arthroscopic visualization with ease. All inside repair was performed using the
      vertical mattress suture configuration. Reduction sutures were subsequently
      removed by cutting flush to the skin and pulling on one suture limb. The patient
      was back to full activities with minimal discomfort 8 months post-operatively.
      CONCLUSION: The technique described is superior to existing techniques for the
      following reasons: (1) Reduction of the displaced meniscal tear is "extra
      meniscal," avoiding further trauma to a damaged meniscus. (2) Tensioning of the
      two suture limbs created promotes better control of reduction through tensioning.
      (3) Risk of discomfort, infection, and neurovascular damage caused by a retained
      suture is reduced. (4) No additional portals/equipment is required. We encourage
      this novel technique to be attempted by surgeons.

PMID- 29202767
TI  - Dose selection for glycopyrrolate/eFlow(r) phase III clinical studies: results
      from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic
      Nebulizer) phase II dose-finding studies.
AB  - BACKGROUND: Long-acting muscarinic antagonists (LAMAs) are recommended for the
      treatment of chronic obstructive pulmonary disease (COPD).
      Glycopyrrolate/eFlow(r) is an investigational drug-device combination of the LAMA
      glycopyrrolate administered by an eFlow(r) Closed System (eFlow(r) CS) nebulizer.
      The GOLDEN 2 (NCT01706536) and GOLDEN 6 (NCT02038829) Phase II, multicenter
      studies were conducted to inform dose selection for the GOLDEN Phase III clinical
      trials. Bronchodilator responses and safety assessments supported dose selection.
      METHODS: Subjects with moderate-to-severe COPD were randomized into 28-day
      parallel-group (GOLDEN 2) or 7-day crossover (GOLDEN 6) studies and received
      placebo, glycopyrrolate (3, 6.25, 12.5, 25, 50 or 100 MUg twice daily [BID]) or
      aclidinium bromide 400 MUg BID. The primary endpoint of both studies was change
      from baseline in trough forced expiratory volume in 1 s (FEV1). Safety
      assessments included the incidence of treatment-emergent adverse events (TEAEs),
      treatment-emergent serious adverse events, and discontinuation due to TEAE. Lung
      function data collected in both studies were pooled. RESULTS: The combined GOLDEN
      2 (n = 282) and GOLDEN 6 (n = 96) studies included 378 subjects. On Days 7 and 28
      there were dose-ordered, statistically significant and clinically important lung
      function improvements in glycopyrrolate treatment groups. Specifically, on Day 7,
      glycopyrrolate produced >0.100 L placebo-adjusted changes from baseline in trough
      FEV1 (12.5 MUg BID: 0.122 L; 25 MUg BID: 0.123 L; 50 MUg BID: 0.137 L) and FEV1
      AUC0-12 (12.5 MUg BID: 0.145 L; 25 MUg BID: 0.178 L; 50 MUg BID: 0.180 L). The
      improvements in lung function for the glycopyrrolate 25 and 50 MUg BID doses were
      comparable to those with aclidinium bromide 400 MUg BID (FEV1: 0.149 L; FEV1 AUC0
      12: 0.172 L). Acceptable safety profiles were observed across all groups in both
      studies. CONCLUSIONS: The efficacy and safety findings supported selection of
      glycopyrrolate 25 and 50 MUg BID doses for the Phase III GOLDEN studies and
      provided preliminary evidence for the use of nebulized glycopyrrolate as a
      maintenance therapy for COPD.

PMID- 29202766
TI  - Transcriptomic analysis of wound xylem formation in Pinus canariensis.
AB  - BACKGROUND: Woody plants, especially trees, usually must face several injuries
      caused by different agents during their lives. Healing of injuries in stem and
      branches, affecting the vascular cambium and xylem can take several years. In
      conifers, healing takes place mainly from the remaining vascular cambium in the
      margin of the wound. The woundwood formed in conifers during healing usually
      presents malformed and disordered tracheids as well as abundant traumatic resin
      ducts. These characteristics affect its functionality as water conductor and its
      technological properties. RESULTS: In this work we analyze for the first time the
      transcriptomic basis of the formation of traumatic wood in conifers, and reveal
      some differences with normal early- and late-wood. Microarray analysis of the
      differentiating traumatic wood, confirmed by quantitative RT-PCR, has revealed
      alterations in the transcription profile of up to 1408 genes during the first
      period of healing. We have grouped these genes in twelve clusters, according to
      their transcription profiles, and have distinguished accordingly two main phases
      during this first healing. CONCLUSIONS: Wounding induces a complete rearrangement
      of the transcriptional program in the cambial zone close to the injuries. At the
      first instance, radial growth is stopped, and a complete set of defensive genes,
      mostly related to biotic stress, are induced. Later on, cambial activity is
      restored in the lateral borders of the wound, even at a high rate. During this
      second stage certain genes related to early-wood formation, including genes
      involved in cell wall formation and transcription factors, are significantly
      overexpressed, while certain late-wood related genes are repressed. Additionally,
      significant alterations in the transcription profile of abundant non annotated
      genes are reported.

PMID- 29202769
TI  - Impact of systolic blood pressure limits on the diagnostic value of triage
      algorithms.
AB  - BACKGROUND: Major incidents are characterized by a lack of resources compared to
      an overwhelming number of casualties, requiring a prioritization of medical
      treatment. Triage algorithms are an essential tool for prioritizing the urgency
      of treatment for patients, but the evidence to support one over another is very
      limited. We determined the influence of blood pressure limits on the diagnostic
      value of triage algorithms, considering if pulse should be palpated centrally or
      peripherally. METHODS: We used a database representing 500 consecutive HEMS
      patients. Each patient was allocated a triage category (T1/red, T2/yellow,
      T3/green) by a group of experienced doctors in disaster medicine, independent of
      any algorithm. mSTaRT, ASAV, Field Triage Score (FTS), Care Flight (CF), "Model
      Bavaria" and two Norwegian algorithms (Nor and TAS), all containing the question
      "Pulse palpable?", were translated into Excel commands, calculating the triage
      category for each patient automatically. We used 5 blood pressure limits ranging
      from 130 to 60 mmHg to determine palpable pulse. The resulting triage categories
      were analyzed with respect to sensitivity, specificity and Youden Index (J)
      separately for trauma and non-trauma patients, and for all patients combined.
      RESULTS: For the entire population of patients within all triage algorithms the
      Youden Index (J) was highest for T1 (J between 0,14 and 0,62). Combining trauma
      and non-trauma patients, the highest J was obtained by ASAV (J = 0,62 at 60
      mmHg). ASAV scored the highest within trauma patients (J = 0,87 at 60 mmHg),
      whereas Model Bavaria (J = 0,54 at 80 mmHg) reached highest amongst non-trauma
      patients. FTS performed worst for all patients (J = 0,14 at 60 mmHg), showing a
      lower score for trauma patients (J = 0,0 at 60 mmHg). Change of blood pressure
      limits resulted in different diagnostic values of all algorithms. DISCUSSION: We
      demonstrate that differing blood pressure limits have a remarkable impact on
      diagnostic values of triage algorithms. Further research is needed to determine
      the lowest blood pressure value that is possible to palpate at a peripheral
      artery compared to a central artery. CONCLUSION: As a consequence, it might be
      important in which location pulses are palpated according to the algorithm at
      hand during triage of patients.

PMID- 29202768
TI  - Assessing the precision of a time-sampling-based study among GPs: balancing
      sample size and measurement frequency.
AB  - BACKGROUND: Our research is based on a technique for time sampling, an innovative
      method for measuring the working hours of Dutch general practitioners (GPs),
      which was deployed in an earlier study. In this study, 1051 GPs were questioned
      about their activities in real time by sending them one SMS text message every 3
      h during 1 week. The required sample size for this study is important for health
      workforce planners to know if they want to apply this method to target groups who
      are hard to reach or if fewer resources are available. In this time-sampling
      method, however, standard power analyses is not sufficient for calculating the
      required sample size as this accounts only for sample fluctuation and not for the
      fluctuation of measurements taken from every participant. We investigated the
      impact of the number of participants and frequency of measurements per
      participant upon the confidence intervals (CIs) for the hours worked per week.
      METHODS: Statistical analyses of the time-use data we obtained from GPs were
      performed. Ninety-five percent CIs were calculated, using equations and
      simulation techniques, for various different numbers of GPs included in the
      dataset and for various frequencies of measurements per participant. RESULTS: Our
      results showed that the one-tailed CI, including sample and measurement
      fluctuation, decreased from 21 until 3 h between one and 50 GPs. As a result of
      the formulas to calculate CIs, the increase of the precision continued and was
      lower with the same additional number of GPs. Likewise, the analyses showed how
      the number of participants required decreased if more measurements per
      participant were taken. For example, one measurement per 3-h time slot during the
      week requires 300 GPs to achieve a CI of 1 h, while one measurement per hour
      requires 100 GPs to obtain the same result. CONCLUSIONS: The sample size needed
      for time-use research based on a time-sampling technique depends on the design
      and aim of the study. In this paper, we showed how the precision of the
      measurement of hours worked each week by GPs strongly varied according to the
      number of GPs included and the frequency of measurements per GP during the week
      measured. The best balance between both dimensions will depend upon different
      circumstances, such as the target group and the budget available.

PMID- 29202770
TI  - A 10-year clinical outcome of radiotherapy as an adjuvant or definitive treatment
      for primary tracheal adenoid cystic carcinoma.
AB  - BACKGROUND: To evaluate the role of radiotherapy (RT) as an adjuvant or
      definitive treatment in primary tracheal adenoid cystic carcinoma (ACC) for local
      tumor control and survival. METHODS: A retrospective chart review was performed
      in 22 patients treated with adjuvant or definitive RT for primary tracheal ACC at
      a single center between November 1994 and December 2008. RESULTS: Thirteen and 9
      patients received adjuvant and definitive RT, respectively. Microscopic residual
      disease after surgery was pathologically reported in 11 patients. The median RT
      dose was 59.4 Gy for adjuvant and 74.4 Gy for definitive RT. The overall response
      rate for definitive RT was 77.8%. Six patients in the definitive RT group
      exhibited local progression (LP), whereas 14 patients in both groups exhibited
      distant metastasis. The most common recurrence site in cases of treatment failure
      was the lung parenchyma. The median follow-up duration was 123 months, and the 10
      year overall survival (OS) rate was 54.2%. Although LP was the most common cause
      of death (4 patients), two-thirds of the patients treated with definitive RT
      lived for >5 years. The 5-year and 10-year LP-free survival (LPFS) rates in the
      definitive RT group were 66.7 and 26.7%, respectively. Patients with higher RT
      dose by brachytherapy boost had good 5-year OS, 83.3%, and showed no local
      progression till 5-years. Most of the RT-induced side-effects were mild and
      tolerable, but 2 patients died of tracheal stenosis without any tumor recurrence.
      CONCLUSIONS: Adjuvant RT may be suitable for controlling microscopic residual
      disease, whereas definitive RT may yield appropriate long-term survival in >50%
      patients with unresectable tracheal ACC. Dose escalation should be considered to
      warrant long-term survival in definitive RT.

PMID- 29202762
TI  - Myocyte membrane and microdomain modifications in diabetes: determinants of
      ischemic tolerance and cardioprotection.
AB  - Cardiovascular disease, predominantly ischemic heart disease (IHD), is the
      leading cause of death in diabetes mellitus (DM). In addition to eliciting
      cardiomyopathy, DM induces a 'wicked triumvirate': (i) increasing the risk and
      incidence of IHD and myocardial ischemia; (ii) decreasing myocardial tolerance to
      ischemia-reperfusion (I-R) injury; and (iii) inhibiting or eliminating responses
      to cardioprotective stimuli. Changes in ischemic tolerance and cardioprotective
      signaling may contribute to substantially higher mortality and morbidity
      following ischemic insult in DM patients. Among the diverse mechanisms implicated
      in diabetic impairment of ischemic tolerance and cardioprotection, changes in
      sarcolemmal makeup may play an overarching role and are considered in detail in
      the current review. Observations predominantly in animal models reveal DM
      dependent changes in membrane lipid composition (cholesterol and triglyceride
      accumulation, fatty acid saturation vs. reduced desaturation, phospholipid
      remodeling) that contribute to modulation of caveolar domains, gap junctions and
      T-tubules. These modifications influence sarcolemmal biophysical properties,
      receptor and phospholipid signaling, ion channel and transporter functions,
      contributing to contractile and electrophysiological dysfunction, cardiomyopathy,
      ischemic intolerance and suppression of protective signaling. A better
      understanding of these sarcolemmal abnormalities in types I and II DM (T1DM,
      T2DM) can inform approaches to limiting cardiomyopathy, associated IHD and their
      consequences. Key knowledge gaps include details of sarcolemmal changes in models
      of T2DM, temporal patterns of lipid, microdomain and T-tubule changes during
      disease development, and the precise impacts of these diverse sarcolemmal
      modifications. Importantly, exercise, dietary, pharmacological and gene
      approaches have potential for improving sarcolemmal makeup, and thus myocyte
      function and stress-resistance in this ubiquitous metabolic disorder.

PMID- 29202771
TI  - Selective proliferative response of microglia to alternative polarization
      signals.
AB  - BACKGROUND: Microglia are resident myeloid cells of the central nervous system
      (CNS) that are maintained by self-renewal and actively participate in tissue
      homeostasis and immune defense. Under the influence of endogenous or pathological
      signals, microglia undertake biochemical transformations that are schematically
      classified as the pro-inflammatory M1 phenotype and the alternatively activated
      M2 state. Dysregulated proliferation of M1-activated microglia has detrimental
      effects, while an increased number of microglia with the alternative, pro
      resolving phenotype might be beneficial in brain pathologies; however, the
      proliferative response of microglia to M2 signals is not yet known. We thus
      evaluated the ability of interleukin-4 (IL-4), a typical M2 and proliferative
      signal for peripheral macrophages, to induce microglia proliferation and compared
      it with other proliferative and M2 polarizing stimuli for macrophages, namely
      colony-stimulating factor-1 (CSF-1) and the estrogen hormone, 17beta-estradiol
      (E2). METHODS: Recombinant IL-4 was delivered to the brain of adult mice by
      intracerebroventricular (i.c.v.) injection; whole brain areas or ex vivo-sorted
      microglia were analyzed by real-time PCR for assessing the mRNA levels of genes
      related with cell proliferation (Ki67, CDK-1, and CcnB2) and M2 polarization
      (Arg1, Fizz1, Ym-1) or by FACS analyses of in vivo BrdU incorporation in
      microglia. Primary cultures of microglia and astrocytes were also tested for
      proliferative effects. RESULTS: Our results show that IL-4 only slightly modified
      the expression of cell cycle-related genes in some brain areas but not in
      microglia, where it strongly enhanced M2 gene expression; on the contrary, brain
      delivery of CSF-1 triggered proliferation as well as M2 polarization of microglia
      both in vivo and in vitro. Similar to IL-4, the systemic E2 administration failed
      to induce microglia proliferation while it increased M2 gene expression.
      CONCLUSIONS: Our data show that, in contrast to the wider responsiveness of
      peripheral macrophages, microglia proliferation is stimulated by selected M2
      polarizing stimuli suggesting a role for the local microenvironment and
      developmental origin of tissue macrophages in regulating self-renewal following
      alternative activating stimuli.

PMID- 29202772
TI  - Evidence use in decision-making on introducing innovations: a systematic scoping
      review with stakeholder feedback.
AB  - BACKGROUND: A range of evidence informs decision-making on innovation in health
      care, including formal research findings, local data and professional opinion.
      However, cultural and organisational factors often prevent the translation of
      evidence for innovations into practice. In addition to the characteristics of
      evidence, it is known that processes at the individual level influence its impact
      on decision-making. Less is known about the ways in which processes at the
      professional, organisational and local system level shape evidence use and its
      role in decisions to adopt innovations. METHODS: A systematic scoping review was
      used to review the health literature on innovations within acute and primary care
      and map processes at the professional, organisational and local system levels
      which influence how evidence informs decision-making on innovation. Stakeholder
      feedback on the themes identified was collected via focus groups to test and
      develop the findings. RESULTS: Following database and manual searches, 31 studies
      reporting primary qualitative data met the inclusion criteria: 24 were of
      sufficient methodological quality to be included in the thematic analysis.
      Evidence use in decision-making on innovation is influenced by multi-level
      processes (professional, organisational, local system) and interactions across
      these levels. Preferences for evidence vary by professional group and health
      service setting. Organisations can shape professional behaviour by requiring
      particular forms of evidence to inform decision-making. Pan-regional
      organisations shape innovation decision-making at lower levels. Political
      processes at all levels shape the selection and use of evidence in decision
      making. CONCLUSIONS: The synthesis of results from primary qualitative studies
      found that evidence use in decision-making on innovation is influenced by
      processes at multiple levels. Interactions between different levels shape
      evidence use in decision-making (e.g. professional groups and organisations can
      use local systems to validate evidence and legitimise innovations, while local
      systems can tailor or frame evidence to influence activity at lower levels).
      Organisational leaders need to consider whether the environment in which
      decisions are made values diverse evidence and stakeholder perspectives. Further
      qualitative research on decision-making practices that highlights how and why
      different types of evidence come to count during decisions, and tracks the
      political aspects of decisions about innovation, is needed.

PMID- 29202774
TI  - Pre-hospital advanced airway management in children: a challenge that training
      can handle.
AB  - We respond to the Tarpgaard et al. article reporting on pre-hospital endotracheal
      intubation (PHETI) success and complications by Danish critical care teams
      including critical care anaesthetists. We compare the authors' results with
      previously published results from our service's experience with PHETI in a
      similar patient population, also with physician and paramedic medical teams. From
      25 children <16 years of age, the Danish study reports overall success, and first
      pass success, and complication rates of 96, 75 and 20%, respectively. A recently
      published study of 82 patients that we completed revealed the following results:
      100, 91 and 14%, respectively. We propose training and operating protocols we
      believe contribute to this relative success in paediatric PHETI.

PMID- 29202773
TI  - Process evaluation of the systematic medical appraisal, referral and treatment
      (SMART) mental health project in rural India.
AB  - BACKGROUND: Availability of basic mental health services is limited in rural
      areas of India. Health system and individual level factors such as lack of mental
      health professionals and infrastructure, poor awareness about mental health,
      stigma related to help seeking, are responsible for poor awareness and use of
      mental health services. We implemented a mental health services delivery model
      that leveraged technology and task sharing to facilitate identification and
      treatment of common mental disorders (CMDs) such as stress, depression, anxiety
      and suicide risk in rural areas of the state of Andhra Pradesh, India. The
      intervention was delivered by lay village health workers (Accredited Social
      Health Activists - ASHAs) and primary care doctors. An anti-stigma campaign was
      implemented prior to this activity. This paper reports the process evaluation of
      the intervention using mixed methods. METHODS: A mixed methods pre-post
      evaluation assessed the intervention using quantitative service usage analytics
      from the server, and qualitative interviews with different stakeholders. Barriers
      and facilitators in implementing the intervention were identified. RESULTS:
      Health service use increased significantly at post-intervention, ASHAs could
      followup 78.6% of those who had screened positive, and 78.6% of the 1243
      Interactive Voice Response System calls made, were successful. Most respondents
      were aware of the intervention. They indicated that knowledge received through
      the intervention empowered them to approach ASHAs and share their mental health
      symptoms. ASHAs and doctors opined that EDSS was useful and easy to use. Medical
      camps organized in villages to increase access to the doctor were received
      positively by all. However, some aspects or facilitators of the intervention need
      to be improved, including network connectivity, booster training, anti-stigma
      campaigns, quality of mental health services provided by doctors, provision of
      psychotropic medications at primary health centers and frequency of health camps.
      CONCLUSION: The respondents' views helped to understand the barriers and
      facilitators for improving the likely effectiveness of the intervention using
      Andersen's Modified Behavioral Model of Health Services Use, and identify the
      mechanisms by which those factors affected mental health services uptake in the
      community. TRIAL REGISTRATION: The study is registered with Clinical Trials
      Registry India (Applied - 16/07/14-Ref2014/07/007256; registration received -
      04/10/17-CTRI/2017/10/009992 ).

PMID- 29202775
TI  - Nam Dia long, a Vietnamese folk formula, induces apoptosis in MCF-7 cells through
      various mechanisms of action.
AB  - BACKGROUND: The holistic approach of traditional medicine renders the
      identification of its mechanisms of action difficult. Microarray technology
      provides an efficient way to analyze the complex genome-wide gene expression of
      cells treated with mixtures of medicinal ingredients. We performed
      transcriptional profiling of MCF-7 cells treated with Nam Dia Long (NDL), a
      Vietnamese traditional formula, to explore the mechanism of action underlying the
      apoptosis inducing effect of this formula reported in a previous study. METHODS:
      MCF-7 cells were treated with aqueous extracts of NDL at the IC50 concentration
      for 24, 36 and 48 h. Total RNAs at 24 h and 48 h were subsequently extracted,
      reverse transcribed and submitted to microarray expression profiling using the
      Human HT-12 v4.0 Expression Bead Chip (Illumina). Functional analyses were
      performed using the Database for Annotation, Visualization and Integrated
      Discovery and the Ingenuity Pathways Analysis. The expression level from selected
      genes at the three time points were assessed by quantitative real-time RT-PCR and
      Western blot. RESULTS: Fifty-four and 601 genes were differentially expressed at
      24 and 48 h of NDL treatment, respectively. Genes with altered expression at 24 h
      were mostly involved in cell responses to xenobiotic stress whereas genes
      differentially expressed at 48 h were related to endoplasmic reticulum stress,
      DNA damage and cell cycle control. Apoptosis of NDL treated MCF-7 cells resulted
      from a combination of different mechanisms including the intrinsic and extrinsic
      pathways, cell cycle arrest- and oxidative stress-related cell death. CONCLUSION:
      NDL elicited a two-stage response in MCF-7 treated cells with apoptosis as the
      ultimate result. The various mechanisms inducing apoptosis reflected the
      complexity of the formula composition.

PMID- 29202776
TI  - 'Image-navigated 3-dimensional late gadolinium enhancement cardiovascular
      magnetic resonance imaging: feasibility and initial clinical results'.
AB  - BACKGROUND: Image-navigated 3-dimensional late gadolinium enhancement (iNAV-3D
      LGE) is an advanced imaging technique that allows for direct respiratory motion
      correction of the heart. Its feasibility in a routine clinical setting has not
      been validated. METHODS: Twenty-three consecutive patients referred for
      cardiovascular magnetic resonance (CMR) examination including late gadolinium
      enhancement (LGE) imaging were prospectively enrolled. Image-navigated free
      breathing 3-dimensional (3D) T1-weighted gradient-echo LGE and two-dimensional
      (2D LGE) images were acquired in random order on a 1.5 T CMR system. Images were
      assessed for global, segmental LGE detection and transmural extent. Objective
      image quality including signal-to-noise (SNR), contrast-to-noise (CNR) and
      myocardial/blood sharpness were performed. RESULTS: Interpretable images were
      obtained in all 2D-LGE and in 22/23 iNAV-3D LGE exams, resulting in a total of 22
      datasets and 352 segments. LGE was detected in 5 patients with ischemic pattern,
      in 7 with non-ischemic pattern, while it was absent in 10 cases. There was an
      excellent agreement between 2D and 3D data sets with regard to global, segmental
      LGE detection and transmurality. Blood-myocardium sharpness measurements were
      also comparable between the two techniques. SNRblood and CNRblood-myo was
      significantly higher for 2D LGE (P < 0.001, respectively), while SNRmyo was not
      statistically significant between 2D LGE and iNAV-3D LGE. CONCLUSION: Diagnostic
      performance of iNAV-3D LGE was comparable to 2D LGE in a prospective clinical
      setting. SNRblood and CNRblood-myo was significantly lower in the iNAV-3D LGE
      group.

PMID- 29202777
TI  - Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically
      in melanoma as a promising target for combination therapy.
AB  - BACKGROUND: Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene
      aberrations has been described in many cancer types. In this study, we aim to
      explore the coexistence status of BRAF V600E mutation and the copy number
      variation of EZH2 and explore the potential of this combination as a therapeutic
      target. METHODS: A total of 138 cases of melanoma samples harboring BRAF V600E
      mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA
      Assays. Clinical pathological distinction between patient groups with or without
      EZH2 amplification (hereafter referred to as EZH2 gain) was statistically
      analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft
      (PDX) models containing BRAF V600E mutation with or without EZH2 gain to
      vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of
      both agents was evaluated. RESULTS: In our cohort, the coexistence rate of BRAF
      V600E mutation and EZH2 gain was up to 29.0%, and significant differences in
      overall survival and disease-free survival were found between no EZH2 copy number
      gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain
      groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed
      better inhibitory efficacy in melanoma prevention compared with vemurafenib
      monotherapy. More importantly, this improved therapeutic effect was observed
      especially in melanoma cell lines and PDX models containing concurrently BRAF
      V600E mutation and EZH2 gain. CONCLUSIONS: Coexistence of BRAF V600E mutation and
      EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the
      feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with
      concurrent BRAF V600E mutation and EZH2 gain.

PMID- 29202778
TI  - Regulator of oligodendrocyte maturation, miR-219, a potential biomarker for MS.
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating and degenerative disease
      of the central nervous system. Normally, demyelination is followed by
      remyelination, which requires repopulation of a demyelinated area by
      oligodendrocyte precursor cells. Although large numbers of precursor cells are
      present in MS lesions, remyelination often fails, in part by the inability of
      precursor cells to differentiate into mature myelin-forming cells. In mouse and
      rat, miR-219 is required for this differentiation. Previously, we identified
      decreased miR-219 expression in tissue of MS patients compared to controls. Cell
      free miRNAs have been detected in many different body fluids including
      cerebrospinal fluid (CSF) and may reflect disease processes going on in the
      central nervous system. This prompted us to investigate the biomarker performance
      of CSF miR-219 for MS diagnosis. METHODS: Quantitative PCR was performed
      measuring miR-219 levels in CSF of MS patients and controls in three independent
      cohorts. RESULTS: All three cohorts of MS patients and controls revealed that
      absence of miR-219 detection in CSF is consistently associated with MS.
      CONCLUSIONS: We have been able to identify and validate absence of miR-219
      detection in CSF of MS patients compared to controls, suggesting that it may
      emerge as a candidate biomarker for MS diagnosis.

PMID- 29202779
TI  - Correlates of poor mental health in early pregnancy in obese European women.
AB  - BACKGROUND: Depression during pregnancy is associated with higher maternal
      morbidity and mortality, and subsequent possible adverse effects on the
      cognitive, emotional and behavioral development of the child. The aim of the
      study was to identify maternal characteristics associated with poor mental
      health, in a group of overweight/obese pregnant women in nine European countries,
      and thus, to contribute to better recognition and intervention for maternal
      depression. METHODS: In this cross-sectional observational study, baseline data
      from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle
      Intervention for gestational diabetes mellitus prevention) study were analyzed.
      Maternal mental health was assessed with the World Health Organization Well-Being
      Index (WHO-5). Women were classified as having a low (WHO-5 <= 50) or high
      wellbeing. RESULTS: A total of 735 pregnant women were included. The prevalence
      of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis
      showed independent associations between low wellbeing and European ethnicity, OR
      = .44, 95% CI [.25, .77], shift work, OR = 1.81, 95% CI [1.11, 2.93],
      insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95%
      CI [.92, .98], social support, OR = .94, 95% CI [.90, .99], and pregnancy-related
      worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI
      [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). CONCLUSIONS: Mental
      health problems are common in European overweight/obese pregnant women. The
      identified correlates might help in early recognition and subsequent treatment of
      poor mental health problems during pregnancy. This is important to reduce the
      unfavorable effects of poor mental health on pregnancy outcomes. TRIAL
      REGISTRATION: ISRCTN70595832 , 02.12.2011.

PMID- 29202780
TI  - Transforming growth factor beta (TGF-beta) in adolescent chronic fatigue
      syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition
      among adolescent. The disease mechanisms are unknown. Previous studies have
      suggested elevated plasma levels of several cytokines, but a recent meta-analysis
      of 38 articles found that of 77 different cytokines measured in plasma,
      transforming growth factor beta (TGF-beta) was the only one that was elevated in
      patients compared to controls in a sufficient number of articles. In the present
      study we therefore compared the plasma levels of the three TGF-beta isoforms in
      adolescent CFS patients and healthy controls. In addition, the study explored
      associations between TGF-beta levels, neuroendocrine markers, clinical markers
      and differentially expressed genes within the CFS group. METHODS: CFS patients
      aged 12-18 years (n = 120) were recruited nation-wide to a single referral center
      as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case
      definition of CFS was applied, requiring 3 months of unexplained, disabling
      chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were
      necessary. Healthy controls (n = 68) were recruited from local schools. The three
      isoforms of TGF-beta (TGF-beta1, TGF-beta2, TGF-beta3) were assayed using
      multiplex technology. Neuroendocrine markers encompassed plasma and urine levels
      of catecholamines and cortisol, as well as heart rate variability indices.
      Clinical markers consisted of questionnaire scores for symptoms of post
      exertional malaise, inflammation, fatigue, depression and trait anxiety, as well
      as activity recordings. Whole blood gene expression was assessed by RNA
      sequencing in a subgroup of patients (n = 29) and controls (n = 18). RESULTS:
      Plasma levels of all three isoforms of TGF-beta were equal in the CFS patients
      and the healthy controls. Subgrouping according to the Fukuda and Canada 2003
      criteria of CFS did not reveal differential results. Within the CFS group, all
      isoforms of TGF-beta were associated with plasma cortisol, urine norepinephrine
      and urine epinephrine, and this association pattern was related to fatigue score.
      Also, TGF-beta3 was related to expression of the B cell annotated genes TNFRSF13C
      and CXCR5. CONCLUSIONS: Plasma levels of all TGF-beta isoforms were not altered
      in adolescent CFS. However, the TGF-beta isoforms were associated with
      neuroendocrine markers, an association related to fatigue score. Furthermore, TGF
      beta3 might partly mediate an association between plasma cortisol and B cell gene
      expression. Trial registration Clinical Trials NCT01040429.

PMID- 29202781
TI  - ACTA2 mutation and postpartum hemorrhage: a case report.
AB  - BACKGROUND: ACTA2 encodes smooth muscle specific alpha-actin, a critical
      component or the contractile complex of vascular smooth muscle. Mutations in
      ACTA2 are the most common genetic cause of thoracic aortic aneurysm, and are also
      the cause of other disorders, including Moyamoya disease, coronary artery disease
      and stroke as well as Multisystemic Smooth Muscle Dysfunction Syndrome. We note
      that ACTA2 is also expressed in uterine smooth muscle, and this raises the
      possibility that women harboring ACTA2 mutations might exhibit uterine smooth
      muscle dysfunction. CASE PRESENTATION: We present a young woman whose ACTA2
      mutation was ascertained during pregnancy because of her father's history of
      dissecting aneurysms. She was delivered at full term by cesarean section and
      subsequently had severe uterine hemorrhage due to uterine atony. Although her
      atony was successfully treated with uterotonic medications, she required blood
      transfusion. CONCLUSIONS: This case raises the possibility that women with ACTA2
      mutations may be at risk of uterine muscle dysfunction and hemorrhage.
      Obstetricians should be alerted to and prepared for this possibility.

PMID- 29202782
TI  - Studying de-implementation in health: an analysis of funded research grants.
AB  - BACKGROUND: Studying de-implementation-defined herein as reducing or stopping the
      use of a health service or practice provided to patients by healthcare
      practitioners and systems-has gained traction in recent years. De-implementing
      ineffective, unproven, harmful, overused, inappropriate, and/or low-value health
      services and practices is important for mitigating patient harm, improving
      processes of care, and reducing healthcare costs. A better understanding of the
      state-of-the-science is needed to guide future objectives and funding
      initiatives. To this end, we characterized de-implementation research grants
      funded by the United States (US) National Institutes of Health (NIH) and the
      Agency for Healthcare Research and Quality (AHRQ). METHODS: We used systematic
      methods to search, identify, and describe de-implementation research grants
      funded across all 27 NIH Institutes and Centers (ICs) and AHRQ from fiscal year
      2000 through 2017. Eleven key terms and three funding opportunity announcements
      were used to search for research grants in the NIH Query, View and Report (QVR)
      system. Two coders identified eligible grants based on inclusion/exclusion
      criteria. A codebook was developed, pilot tested, and revised before coding the
      full grant applications of the final sample. RESULTS: A total of 1277 grants were
      identified through the QVR system; 542 remained after removing duplicates. After
      the multistep eligibility assessment and review process, 20 grant applications
      were coded. Many grants were funded by NIH (n = 15), with fewer funded by AHRQ,
      and a majority were funded between fiscal years 2015 and 2016 (n = 11). Grant
      proposals focused on de-implementing a range of health services and practices
      (e.g., medications, therapies, screening tests) across various health areas
      (e.g., cancer, cardiovascular disease) and delivery settings (e.g., hospitals,
      nursing homes, schools). Grants proposed to use a variety of study designs and
      research methods (e.g., experimental, observational, mixed methods) to accomplish
      study aims. CONCLUSIONS: Based on the systematic portfolio analysis of NIH- and
      AHRQ-funded research grants over the past 17 years, relatively few have focused
      on studying the de-implementation of ineffective, unproven, harmful, overused,
      inappropriate, and/or low-value health services and practices provided to
      patients by healthcare practitioners and systems. Strategies for raising the
      profile and growing the field of research on de-implementation are discussed.

PMID- 29202783
TI  - Influences on anticipated time to ovarian cancer symptom presentation in women at
      increased risk compared to population risk of ovarian cancer.
AB  - BACKGROUND: In the absence of routine ovarian cancer screening, promoting help
      seeking in response to ovarian symptoms is a potential route to early diagnosis.
      The factors influencing women's anticipated time to presentation with potential
      ovarian cancer symptoms were examined. METHODS: Cross-sectional questionnaires
      were completed by a sample of women at increased familial risk (n = 283) and
      population risk (n = 1043) for ovarian cancer. Measures included demographic
      characteristics, symptom knowledge, anticipated time to symptom presentation, and
      health beliefs (perceived susceptibility, worry, perceived threat, confidence in
      symptom detection, benefits and barriers to presentation). Structural equation
      modelling was used to identify determinants of anticipated time to symptomatic
      presentation in both groups. RESULTS: Associations between health beliefs and
      anticipated symptom presentation differed according to risk group. In increased
      risk women, high perceived susceptibility (r = .35***), ovarian cancer worry (r =
      .98**), perceived threat (r = -.18**), confidence (r = .16**) and perceiving more
      benefits than barriers to presentation (r = -.34**), were statistically
      significant in determining earlier anticipated presentation. The pattern was the
      same for population risk women, except ovarian cancer worry (r = .36) and
      perceived threat (r = -.03) were not statistically significant determinants.
      CONCLUSIONS: Associations between underlying health beliefs and anticipated
      presentation differed according to risk group. Women at population risk had
      higher symptom knowledge and anticipated presenting in shorter time frames than
      the increased risk sample. The cancer worry component of perceived threat was a
      unique predictor in the increased risk group. In increased risk women, the worry
      component of perceived threat may be more influential than susceptibility aspects
      in influencing early presentation behaviour, highlighting the need for ovarian
      symptom awareness interventions with tailored content to minimise cancer-related
      worry in this population.

PMID- 29202784
TI  - Sprint and jump performance in elite male soccer players following a 10-week
      Nordic Hamstring exercise Protocol: a randomised pilot study.
AB  - OBJECTIVE: The preseason Nordic Hamstring Protocol (NHP) reduces hamstring strain
      injuries in football players. Despite persisting injury rates, elite clubs are
      reluctant to apply the NHP often over concerns of negative impacts on
      performance. This pilot study investigated if sprint or jump-performance outcomes
      tended to increase or decrease following implementation of the NHP in elite male
      soccer-players. RESULTS: Nineteen male soccer players from the Danish 1st
      division were randomised to perform NHP (27 sessions) during pre-season, or to
      control group (CG). Sprint performance (30 m with 5 and 10 m split times) and
      countermovement jump (CMJ height) was measured before the mid-seasonal break and
      again after 10 weeks of performing the NHP at the end of pre-season. Dropouts
      were due to transfers and injuries unrelated to performing NHP (NHP = 0, CG = 5).
      Sprint performance on the short split distances improved for most players in the
      NHP (6 out of 9 improved, median changes for 5 m split: - 0.068 s; 10 m split: -
      0.078 s), but not CG (2 out of 5 improved, median changes for 5 m split: + 0.1 s;
      10 m split: CG: + 0.11 s), but both groups had small declines at 30 m sprint
      (NHP: 7 out of 9 declined, median changes: + 0.116 s; CG: 4 out of 5 declined,
      median changes: + 0.159 s). CMJ height mostly improved in both groups (NHP: 6 out
      of 9 improved, median changes: + 2.1 cm; CG: 4 out of 8 improved, median changes:
      + 0.55 cm). Performing the NHP in elite soccer players did therefore not seem to
      negatively affect sprint and vertical jump performance outcomes in the present
      study, while in fact showing some promise for the more explosive characteristics
      such as the short 5 and 10 m split-times and maximal CMJ height, which all are
      highly relevant performance parameters in elite football.

PMID- 29202785
TI  - Anti-aggregant tau mutant promotes neurogenesis.
AB  - BACKGROUND: The microtubule-associated protein Tau plays a role in
      neurodegeneration as well as neurogenesis. Previous work has shown that the
      expression of the pro-aggregant mutant Tau repeat domain causes strong
      aggregation and pronounced neuronal loss in the hippocampus whereas the anti
      aggregant form has no deleterious effects. These two proteins differ mainly in
      their propensity to form beta structure and hence to aggregate. METHODS: To
      elucidate the basis of these contrasting effects, we analyzed organotypic
      hippocampal slice cultures (OHSCs) from transgenic mice expressing the repeat
      domain (RD) of Tau with the anti-aggregant mutation (TauRDDeltaKPP) and compared
      them with slices containing pro-aggregant TauRDDeltaK. Transgene expression in
      the hippocampus was monitored via a sensitive bioluminescence reporter gene assay
      (luciferase). RESULTS: The expression of the anti-aggregant TauRDDeltaKPP leads
      to a larger volume of the hippocampus at a young age due to enhanced
      neurogenesis, resulting in an increase in neuronal number. There were no signs of
      activation of microglia and astrocytes, indicating the absence of an inflammatory
      reaction. Investigation of signaling pathways showed that Wnt-5a was strongly
      decreased whereas Wnt3 was increased. A pronounced increase in hippocampal stem
      cell proliferation (seen by BrdU) was observed as early as P8, in the CA regions
      where neurogenesis is normally not observed. The increase in neurons persisted up
      to 16 months of age. CONCLUSION: The data suggest that the expression of anti
      aggregant TauRDDeltaKPP enhances hippocampal neurogenesis mediated by the
      canonical Wnt signaling pathway, without an inflammatory reaction. This study
      points to a role of tau in brain development and neurogenesis, in contrast to its
      detrimental role in neurodegeneration at later age.

PMID- 29202786
TI  - PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for
      patients admitted to acute settings with hip fracture identified as experiencing
      confusion: study protocol for a feasibility cluster randomized controlled trial.
AB  - BACKGROUND: Health and social care provision for an ageing population is a global
      priority. Provision for those with dementia and hip fracture has specific and
      growing importance. Older people who break their hip are recognised as
      exceptionally vulnerable to experiencing confusion (including but not
      exclusively, dementia and/or delirium and/or cognitive impairment(s)) before,
      during or after acute admissions. Older people experiencing hip fracture and
      confusion risk serious complications, linked to delayed recovery and higher
      mortality post-operatively. Specific care pathways acknowledging the differences
      in patient presentation and care needs are proposed to improve clinical and
      process outcomes. METHODS: This protocol describes a multi-centre, feasibility,
      cluster-randomised, controlled trial (CRCT) to be undertaken across ten National
      Health Service hospital trusts in the UK. The trial will explore the feasibility
      of undertaking a CRCT comparing the multicomponent PERFECTED enhanced recovery
      intervention (PERFECT-ER), which acknowledges the differences in care needs of
      confused older patients experiencing hip fracture, with standard care. The trial
      will also have an integrated process evaluation to explore how PERFECT-ER is
      implemented and interacts with the local context. The study will recruit 400 hip
      fracture patients identified as experiencing confusion and will also recruit
      "suitable informants" (individuals in regular contact with participants who will
      complete proxy measures). We will also recruit NHS professionals for the process
      evaluation. This mixed methods design will produce data to inform a definitive
      evaluation of the intervention via a large-scale pragmatic randomised controlled
      trial (RCT). DISCUSSION: The trial will provide a preliminary estimate of
      potential efficacy of PERFECT-ER versus standard care; assess service delivery
      variation, inform primary and secondary outcome selection, generate estimates of
      recruitment and retention rates, data collection difficulties, and completeness
      of outcome data and provide an indication of potential economic benefits. The
      process evaluation will enhance knowledge of implementation delivery and receipt.
      TRIAL REGISTRATION: ISRCTN, 99336264 . Registered on 5 September 2016.

PMID- 29202787
TI  - Efficacy and safety of eribulin in patients with locally advanced or metastatic
      breast cancer not meeting trial eligibility criteria: a retrospective study.
AB  - BACKGROUND: The efficacy and safety of eribulin in patients with locally advanced
      or metastatic breast cancer has been demonstrated in phase III trials. However,
      as patients receiving eribulin in daily practice do not necessarily meet all the
      eligibility criteria of clinical trials, data for such patients are limited.
      METHODS: We identified patients with locally advanced or metastatic breast
      cancer, treated with eribulin monotherapy between July 2011 and December 2015 at
      the National Cancer Center Hospital, Tokyo, Japan. Patients who would have met
      the following eligibility criteria from the EMBRACE trial were included in the
      eligible group, and the rest were included in the ineligible group: 1) Eastern
      Cooperative Oncology Group Performance status 0-2; 2) adequate function of
      principal organs; and 3) absence of active infection. We compared the relative
      dose intensity (RDI), tumor response, progression-free survival (PFS), overall
      survival (OS), and adverse events between the groups. Nominal and continuous
      values were compared using the Fisher's exact test and Mann-Whitney U test,
      respectively. Survival outcomes were determined using Kaplan-Meier estimation,
      and between-group differences were assessed using the log-rank test. RESULTS: Of
      the 203 patients included, 34 were classified into the ineligible group and 169
      into the eligible group. Initial dose reduction and treatment discontinuation due
      to adverse events (AEs) were more common in the ineligible group (initial dose
      reduction: 23.5% in the ineligible group vs. 7.7% in the eligible group, p =
      0.011; treatment discontinuation due to AEs: 11.8% vs. 3.0%, p = 0.045). However,
      RDI (66% vs. 71%, p = 0.130), response rate (15.6% vs. 18.1%, p = 1.000), PFS
      (3.7 months vs. 4.0 months, p = 0.913), OS (11.5 months vs. 16.1 months, p =
      0.743), AEs requiring hospitalization (5.9% vs. 6.5%, p = 1.000), and grade 3/4
      AEs were similar in both groups. PFS, OS, AEs requiring hospitalization, and
      discontinuation due to AEs in the eligible group were comparable to those found
      in previous phase III trials. CONCLUSION: The safety and efficacy of eribulin
      monotherapy was demonstrated in a broader patient population than that eligible
      for clinical trials. Eribulin may be a treatment option in these patients with
      locally advanced or metastatic breast cancer, considering dose reduction and pre
      existing dysfunctions.

PMID- 29202788
TI  - MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta
      analysis from 16 case-control studies.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in
      the hyperhomocysteinemia, which is a risk factor related to the occurrence of
      congenital heart defect (CHD). However, the association between MTHFR
      polymorphism and CHD has been inconclusive. METHODS: We conducted an updated meta
      analysis to provide comprehensive evidence on the role of MTHFR A1298C
      polymorphism in CHD. Databases were searched and a total of 16 studies containing
      2207 cases and 2364 controls were included. RESULTS: We detected that a
      significant association was found in the recessive model (CC vs. AA + AC: OR =
      1.38, 95% CI: 1.10-1.73) for the overall population. Subgroup analysis showed
      that associations were found in patients without Down Syndrome in genetic models
      for CC vs. AA (OR = 1.47, 95% CI: 1.01-2.14), CC vs. AC (OR = 1.29, 95% CI: 1.00
      1.66) and recessive model (OR = 1.44, 95% CI: 1.14-1.82). We conducted a meta
      regression analysis, Galbraith plots and a sensitivity analysis to assess the
      sources of heterogeneity. CONCLUSIONS: In summary, our present meta-analysis
      supports the MTHFR 1298C allele as a risk factor for CHD. However, further
      studies should be conducted to investigate the correlation of plasma homocysteine
      levels, enzyme activity, and periconceptional folic acid supplementation with the
      risk of CHD.

PMID- 29202789
TI  - Paracetamol clinical dosing routine leads to paracetamol underexposure in an
      adult severely ill sub-Saharan African hospital population: a drug concentration
      measurement study.
AB  - BACKGROUND: Hospitals in sub-Saharan Africa (SSA) continue to receive high
      numbers of severely ill (HIV-infected) patients with physical pain that may
      suffer from hepatic and renal dysfunction. Paracetamol is widely used for pain
      relief in this setting but it is unknown whether therapeutic drug concentrations
      are attained. The aim of this study was to assess the occurrence of therapeutic,
      sub-therapeutic and toxic paracetamol concentrations in SSA adult hospital
      population. METHODS: In a cross-sectional study, plasma paracetamol
      concentrations were measured in patients with an oral prescription in a referral
      hospital in Mozambique. From August to November 2015, a maximum of four blood
      samples were drawn on different time points for paracetamol concentration
      measurement and biochemical analysis. Study endpoints were the percentage of
      participants with therapeutic (>= 10 and <= 20 mg/L), sub-therapeutic (< 10 mg/L)
      and toxic (> 75 mg/L) concentrations. RESULTS: Seventy-six patients with a median
      age of 37 years, a body mass index of 18.2, a haemoglobin concentration of 10.3
      g/dL and an albumin of 29 g/L yielded 225 samples. 13.4% of participants had one
      or more therapeutic paracetamol concentrations. 86.6% had a sub-therapeutic
      concentration at all time points and 70.2% had two or more concentrations below
      the lower limit of quantification. No potentially toxic concentrations were
      found. CONCLUSIONS: Routine oral dosing practices in a SSA hospital resulted in
      substantial underexposure to paracetamol. Palliation is likely to be sub-standard
      and oral palliative drug pharmacokinetics and dispensing procedures in this
      setting need further investigation.

PMID- 29202790
TI  - Depression: point-prevalence and risk factors in a North Cyprus household adult
      cross-sectional study.
AB  - BACKGROUND: Depression is one of the most common diagnosed psychiatric disorders
      in the world. Besides individual risk factors, it is also found that environment
      and socio-cultural factors are the other main risk factors for depression. In
      this article, the results of the 2016 national household survey of depression in
      North Cyprus (NC) are presented. The aim of the study is to determine the
      prevalence and possible risk factors of depression in NC households. METHODS: The
      study was conducted between April and June 2016, the sample consisting of Turkish
      speaking individuals between 18 and 88 years of age living permanently in NC. A
      multi-stage stratified (randomized) quota was used in the survey, and 978 people
      were selected according to the 2011 census. A 21 item questionnaire prepared by
      the researchers and a Turkish version of the Beck Depression Inventory scales
      were used for obtaining data. RESULTS: This cross-sectional study found a point
      prevalence of 23.4% for relatively high BDI scores (>=17) suggesting clinical
      depression. Being female, a widow, unemployed, having a limited education and low
      income level, having a physical illness, living alone, and using illicit
      substances were defined as possible risk factors for depression. CONCLUSIONS:
      When we consider the world prevalence, NC has one of the higher depression
      prevalence. NC has environmental and socio-cultural characteristics such as a
      history of war, migration and colonization, high unemployment rates,
      socioeconomic problems, similar to other extremely high prevalence depression
      countries and regions, which give a strong indication of the importance of socio
      cultural factors on depression.

PMID- 29202791
TI  - Factors associated with unwillingness to seek professional help for depression: a
      web-based survey.
AB  - OBJECTIVE: Depression is a prevalent disorder that has a substantial impact on
      not only individuals but also society as a whole. Despite many effective
      depression interventions, delay in initial treatment contact is problematic. The
      Internet is a possible tool for low-cost dissemination of appropriate information
      and awareness raising about depressive disorders among the general public. This
      study aimed to identify factors associated with unwillingness to seek
      professional help for depression in Internet users. RESULTS: This web-based cross
      sectional study surveyed 595 participants who scored over the cutoff point for
      depression on a self-rated mental-health questionnaire for depression, had never
      been assessed or treated by a mental health professional, and were experiencing
      depressive symptoms for at least 6 months. Among the 595 participants, 329
      (55.3%) reported they were unwilling to seek professional help for depression.
      Regression analysis indicated that unwillingness to seek professional help for
      depression was associated with male sex and financial issues as a depression
      trigger, and that willingness to seek professional help was associated with
      problems with interpersonal relationships. The Internet warrants further
      complementary investigation to elucidate factors associated with unwillingness to
      seek professional help for depression.

PMID- 29202792
TI  - The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can
      be downregulated by minocycline: possible implications for long-term treatment of
      HTLV-1-associated myelopathy/tropical spastic paraparesis.
AB  - BACKGROUND: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated
      monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2
      cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated
      that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine
      anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that
      plays a major role in inflammatory processes, we investigated the role of CCL1 in
      the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). RESULTS: The results showed
      that: (1) CCL1 was preferentially expressed in HAM/TSP-derived HTLV-1-infected T
      cell lines, (2) CCL1 expression was induced along with Tax expression in the Tax
      inducible T-cell line JPX9, (3) transient Tax expression in an HTLV-1-negative T
      cell line activated the CCL1 gene promoter, (4) plasma levels of CCL1 were
      significantly higher in patients with HAM/TSP than in HTLV-1-seronegative
      patients with multiple sclerosis and HTLV-1-infected asymptomatic healthy
      carriers, and (5) minocycline inhibited the production of CCL1 in HTLV-1-infected
      T-cell lines. CONCLUSIONS: The present results suggest that elevated CCL1 levels
      may be associated with the pathogenesis of HAM/TSP. Although further studies are
      required to determine the in vivo significance, minocycline may be considered as
      a potential candidate for the long-term treatment of HAM/TSP via its anti
      inflammatory effects, which includes the inhibition of CCL1 expression.

PMID- 29202793
TI  - Androgen receptor CAG repeat polymorphism is not associated with insulin
      resistance and diabetes among South Asian males.
AB  - OBJECTIVE: To study relationship between androgen receptor (AR) CAG repeat
      polymorphism, insulin resistance (IR), beta-cell function and other
      clinical/biochemical parameters in ethnic South Asian adults. A case (males with
      diabetes), control (males without diabetes) study, was conducted and 110 males
      were invited. Anthropometry, blood pressure and biochemical parameters (fasting
      Insulin, blood sugar, HbA1c and lipid profile) were measured. IR and beta-cell
      function was calculated. A multiple-linear-regression analysis was performed,
      using number of AR CAG repeats as the continuous dependent variable. RESULTS:
      Sample size was 100 (response rate-90.9%, cases-53). Mean age was 49.6 +/- 10.7
      years. CAG repeat length did not show any significant correlation with IR or beta
      cell function. In all males there was a significant correlation between number of
      AR CAG repeats and systolic blood pressure (r = 0.25; p = 0.016), diastolic blood
      pressure (r = 0.21; p = 0.045), total cholesterol (r = - 0.22; p = 0.037) and low
      density lipoprotein cholesterol (r = - 0.22; p = 0.037). Only total cholesterol
      (beta = - 4.41; p < 0.001) and estrogen (beta = 2.25; p = 0.03) were
      significantly associated with number of AR CAG repeats in regression analysis. In
      conclusion, AR CAG repeat length did not show any significant correlation with IR
      or beta-cell function. Positive association of AR CAG with systolic and diastolic
      blood pressure and negative association of AR CAG with total and low-density
      lipoprotein cholesterol deserves further attention.

PMID- 29202794
TI  - Predictors of poor blood pressure control among Iranian hypertensive patients.
AB  - OBJECTIVE: The aim of this study is to investigate factors associated with poor
      blood pressure (BP) control in older hypertensive patients living in Iran. Poorly
      controlled hypertension was defined as blood pressure greater than or equal to
      140/90 mmHg. Multiple logistic regressions were performed to identify factors
      associated with poor BP control. RESULTS: More than half of the patients (55.1%)
      had poor control of hypertension. Multivariate logistic regression analysis
      showed that being over 60 years of age (OR 1.67; 95% CI 1.18-2.37; p = .003),
      being widowed or divorced (OR 1.56; 95% CI 1.03-2.35; p = .035], smoking (OR
      1.78; 95% CI 1.07-2.65; p = .01], BMI > 25 kg/m2 (OR 1.51 95% CI 1.05-2.78),
      having a waist circumference >= 90 cm (OR 1.7; 95% CI 1.2-2.42; p = .003], the
      use of calcium channel blockers (OR 2.69; 95% CI 1.26-5.72; p = .01], and the use
      of angiotensin converting enzyme inhibitors (OR 1.66; 95% CI 1.01-2.72; p = .044]
      contributed significantly to poor control of hypertension. Making a key BP
      control screening target (such as age over 60 and waist circumference of 90 cm or
      more) for cardiovascular specialists and other health care practitioners is
      needed for elderly patients at risk for poor BP control.

PMID- 29202795
TI  - Validation of an algorithm that determines stroke diagnostic code accuracy in a
      Japanese hospital-based cancer registry using electronic medical records.
AB  - BACKGROUND: This study aimed to validate an algorithm that determines stroke
      diagnostic code accuracy, in a hospital-based cancer registry, using electronic
      medical records (EMRs) in Japan. METHODS: The subjects were 27,932 patients
      enrolled in the hospital-based cancer registry of Osaka University Hospital,
      between January 1, 2007 and December 31, 2015. The ICD-10 (international
      classification of diseases, 10th revision) diagnostic codes for stroke were
      extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60);
      intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient
      cerebral ischemic attacks and related syndromes and transient cerebral ischemic
      attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both
      "definite" and "suspected," and brain imaging information were extracted from the
      database. We set the algorithm with the combination of the diagnostic code and/or
      the brain imaging information, and manually reviewed the presence or absence of
      the acute cerebrovascular disease with medical charts. RESULTS: A total of 2654
      diagnostic codes, 1991 "definite" and 663 "suspected," were identified. After
      excluding duplicates, the numbers of "definite" and "suspected" diagnostic codes
      were 912 and 228, respectively. The proportion of the presence of the disease in
      the "definite" diagnostic code was 22%; this raised 51% with the combination of
      the diagnostic code and the use of brain imaging information. When adding the
      interval of when brain imaging was performed (within 30 days and within 1 day) to
      the diagnostic code, the proportion increased to 84% and 90%, respectively. In
      the algorithm of "definite" diagnostic code, history of stroke was the most
      common in the diagnostic code, but in the algorithm of "definite" diagnostic code
      and the use of brain imaging within 1 day, stroke mimics was the most frequent.
      CONCLUSIONS: Combining the diagnostic code and clinical examination improved the
      proportion of the presence of disease in the diagnostic code and achieved
      appropriate accuracy for research. Clinical research using EMRs require outcome
      validation prior to conducting a study.

PMID- 29202796
TI  - Discharge service as a determinant of 30-day readmission in a cohort of
      maintenance hemodialysis patients: a retrospective cohort study.
AB  - BACKGROUND: End stage renal disease (ESRD) patients on maintenance hemodialysis,
      are high utilizers of inpatient services. Because of data showing improved
      outcomes in medical patients admitted to hospitalist-run, non-teaching services,
      we hypothesized that discharge from a hospitalist-run, non-teaching service is
      associated with lower risk of 30-day re-hospitalization in a cohort of patients
      on hemodialysis. METHODS: One thousand and 84 consecutive patients with ESRD on
      maintenance hemodialysis who were admitted to Montefiore, a tertiary care center,
      in 2014 were analyzed using the electronic medical records. We evaluated factors
      associated with 30-day readmission in multivariable regression models. We then
      tested the association of care by a hospitalist-run, non-teaching service with 30
      day readmission in a propensity score matched analysis. RESULTS: Patients cared
      for on the hospitalist-run, non-teaching service had lower socio-economic scores
      (SES) and had longer lengths of stay (LOS), as compared to a standard teaching
      service, but otherwise the populations were similar. In multivariable testing,
      severity of illness, (OR 2.40, (95%CI: 1.43-4.03) for highest quartile) number of
      previous hospitalizations (OR 1.22 (95%CI:1.16-1.28) for each admission), and
      discharge to a skilled nursing facility (SNF)(OR 1.56 (95%CI:1.01-2.43) were
      significantly associated with 30-day re-admissions. Care by the non-teaching
      service was associated with a lower risk of 30-day readmission, even after
      adjusting for clinical factors and matching based on propensity score (OR
      0.65(95%CI:0.46-0.91) and 0.71(95%CI:0.66-0.77) respectively). CONCLUSIONS:
      Patients with ESRD on hemodialysis discharged from a hospitalist-run, non
      teaching medicine service had lower odds of readmission as compared to those
      patients discharged from a standard teaching service.

PMID- 29202797
TI  - Clinical and economic impact of the introduction of a nucleic acid amplification
      assay for Clostridium difficile.
AB  - BACKGROUND: The clinical outcomes and cost implications of a diagnostic shift
      from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have
      not been completely described in the literature. METHODS: The impact of the PCR
      based assay on the incidence and duration of CDI therapy was compared to the EIA
      assay for patients with a negative CDI diagnostic result. Secondary clinical and
      economic outcomes were also evaluated. Independent predictors of receipt of
      antibiotic therapy were assessed via logistic regression. RESULTS: 141 EIA and
      140 PCR patients were included. Significantly more patients were started or
      continued on anti-CDI antibiotic therapy after a known negative assay result in
      the EIA group (26 patients vs. 8 patients, P = 0.002). Duration of antibiotic
      therapy after a known negative result was significantly shorter in the PCR group
      (1 vs. 4 days, P = 0.029) and a 23% reduction in the number of tests obtained per
      patient was observed (1.41 +/- 0.86 vs. 1.82 +/- 1.35, P = 0.007). The over
      fourfold difference in per-test cost of the EIA assay ($8.33 vs. $42.86, P <
      0.0001) was offset by the overall medication costs required for the increased
      treatment in the EIA group ($546.60 vs. $188.96, P = 0.191). Utilization of the
      EIA-based CDI assay was associated with increased odds of CDI treatment after a
      negative test (aOR 4.71, 95% CI 1.93-11.46, P = 0.001). CONCLUSION: The
      transition from an EIA to PCR-based assay for diagnosing CDI resulted in a
      significant decrease in the number of patients treated and the duration of
      treatment in response to a negative test result. This significant decrease in
      treatment resulted in decreased costs offsetting the utilization of a more
      expensive molecular test for patients with a negative CDI diagnostic result.

PMID- 29202798
TI  - Intention to vaccinate universally against varicella, rotavirus gastroenteritis,
      meningococcal B disease and seasonal influenza among parents in the Netherlands:
      an internet survey.
AB  - OBJECTIVE: For the decision-making process regarding introduction of new vaccines
      into the National Immunisation Programme (NIP), advance insight into the
      potential acceptance among the population is relevant. We studied the intention
      of parents to have their child vaccinated against four diseases not currently
      covered by the NIP in the Netherlands. The results on varicella have been
      published before; this article adds the results on vaccination against rotavirus
      gastroenteritis, meningococcal B disease, and seasonal influenza. RESULTS: We
      invited a random sample from the national immunisation register of 1500 parents
      for an internet survey which was completed by 491 parents (33% response). The
      intention to vaccinate was highest for meningococcal B disease (83% positive
      intention), followed by rotavirus gastroenteritis (38%), and lowest for varicella
      (28%) and seasonal influenza (15%). Prediction analyses were performed to
      determine which out of seven questionnaire statements was most informative in
      predicting the intention to vaccinate. Main drivers of intention were the
      perceived importance of vaccination against the particular disease and the
      perception of whether or not the disease is severe enough to justify vaccination.
      The results of this study can be informative in the decision-making process
      whether or not to introduce new vaccines into the NIP.

PMID- 29202799
TI  - Routine blood tests and probability of cancer in patients referred with non
      specific serious symptoms: a cohort study.
AB  - BACKGROUND: Danish cancer patients have lower survival rates than patients in
      many other western countries. Half of the patients present with non-alarm
      symptoms and thus have a long diagnostic pathway. Consequently, an urgent
      referral pathway for patients with non-specific serious symptoms was implemented
      throughout Denmark in 2011-2012. As part of the diagnostic workup, a panel of
      blood tests are performed for all patients referred by their general practitioner
      (GP) to the urgent referral pathway. In this study, we analysed the probability
      of being diagnosed with cancer in GP-referred patients with abnormal blood test
      results. METHOD: We performed a cohort study that included all patients aged 18
      years or older referred by their GP to Silkeborg Regional Hospital for analysis
      of a panel of blood tests. All patients were followed for 3 months for a cancer
      diagnosis in the Danish Cancer Registry. The likelihood ratio and post-test
      probability of subsequently finding cancer were calculated in relation to
      abnormal blood test results. RESULTS: Among the 1499 patients included in the
      study, 12.2% were subsequently diagnosed with cancer. The probability of cancer
      increased with the number of abnormal blood tests. Patients with specific
      combinations of two abnormal blood tests had a 23-62% probability of cancer. Only
      a few single abnormal blood tests were linked with a high post-test probability
      of cancer, and most abnormalities were not specific to cancer. CONCLUSIONS: A
      number of specific abnormal blood tests and combinations of abnormal blood tests
      markedly increased the probability of cancer being diagnosed. Still, abnormal
      blood test results should be interpreted cautiously as most are non-specific to
      cancer. Thus, results from the blood test panel may strengthen the suspicion of
      cancer, but blood tests cannot be used as a stand-alone tool to rule out cancer.

PMID- 29202801
TI  - Applying quantitative bias analysis to estimate the plausible effects of
      selection bias in a cluster randomised controlled trial: secondary analysis of
      the Primary care Osteoarthritis Screening Trial (POST).
AB  - BACKGROUND: Selection bias is a concern when designing cluster randomised
      controlled trials (c-RCT). Despite addressing potential issues at the design
      stage, bias cannot always be eradicated from a trial design. The application of
      bias analysis presents an important step forward in evaluating whether trial
      findings are credible. The aim of this paper is to give an example of the
      technique to quantify potential selection bias in c-RCTs. METHODS: This analysis
      uses data from the Primary care Osteoarthritis Screening Trial (POST). The
      primary aim of this trial was to test whether screening for anxiety and
      depression, and providing appropriate care for patients consulting their GP with
      osteoarthritis would improve clinical outcomes. Quantitative bias analysis is a
      seldom-used technique that can quantify types of bias present in studies. Due to
      lack of information on the selection probability, probabilistic bias analysis
      with a range of triangular distributions was also used, applied at all three
      follow-up time points; 3, 6, and 12 months post consultation. A simple bias
      analysis was also applied to the study. RESULTS: Worse pain outcomes were
      observed among intervention participants than control participants (crude odds
      ratio at 3, 6, and 12 months: 1.30 (95% CI 1.01, 1.67), 1.39 (1.07, 1.80), and
      1.17 (95% CI 0.90, 1.53), respectively). Probabilistic bias analysis suggested
      that the observed effect became statistically non-significant if the selection
      probability ratio was between 1.2 and 1.4. Selection probability ratios of > 1.8
      were needed to mask a statistically significant benefit of the intervention.
      CONCLUSIONS: The use of probabilistic bias analysis in this c-RCT suggested that
      worse outcomes observed in the intervention arm could plausibly be attributed to
      selection bias. A very large degree of selection of bias was needed to mask a
      beneficial effect of intervention making this interpretation less plausible.

PMID- 29202800
TI  - Genistein induces apoptosis of colon cancer cells by reversal of epithelial-to
      mesenchymal via a Notch1/NF-kappaB/slug/E-cadherin pathway.
AB  - BACKGROUND: Genistein has been known to inhibit proliferation and induce
      apoptosis in several kinds of cancer cells. While knowledge of genistein in
      regulating epithelial mesenchymal transition (EMT) of colon cancer cells is
      unknown. METHODS: To investigate the effects and mechanisms of genistein on EMT
      of colon cancer cells, HT-29 cells were used and treated by genistein and TNF
      alpha in this paper. EMT was determined by cell invasion assays using a transwell
      chamber and the expression changes of EMT-related markers were confirmed by RT
      PCR, Western blotting, and immunofluorescence staining. RESULTS: Genistein
      inhibited cell migration at 200 MUmol/L. Genistein reversed the EMT of colon
      cancer cells by upregulation of E-cadherin and downregulation of N-cadherin,
      accompanied by the suppression of EMT related makers, such as Snail2/slug, ZEB1,
      ZEB2, FOXC1, FOXC2 and TWIST1. Moreover, genistein can inhibit the expression of
      notch-1, p-NF-kappaB and NF-kappaB, while promote the expression of Bax/Bcl-2 and
      caspase-3 in HT-29 cells. CONCLUSION: The present study demonstrated that
      genistein suppressed the migration of colon cancer cells by reversal the EMT via
      suppressing the Notch1/NF-kappaB/slug/E-cadherin pathway. Genistein may be
      developed as a potential antimetastasis agent to colon cancer.

PMID- 29202802
TI  - Histopathology, microbiology and the inflammatory process associated with
      Sarcoptes scabiei infection in the Iberian ibex, Capra pyrenaica.
AB  - BACKGROUND: Sarcoptic mange has been identified as the most significant
      infectious disease affecting the Iberian ibex (Capra pyrenaica). Despite several
      studies on the effects of mange on ibex, the pathological and clinical picture
      derived from sarcoptic mange infestation is still poorly understood. To further
      knowledge of sarcoptic mange pathology, samples from ibex were evaluated from
      histological, microbiological and serological perspectives. METHODS: Samples of
      skin, non-dermal tissues and blood were collected from 54 ibex (25 experimentally
      infected, 15 naturally infected and 14 healthy). Skin biopsies were examined at
      different stages of the disease for quantitative cellular, structural and
      vascular changes. Sixteen different non-dermal tissues of each ibex were taken
      for histological study. Acetylcholinesterase and serum amyloid A protein levels
      were evaluated from blood samples from ibex with different lesional grade.
      Samples of mangy skin, suppurative lesions and internal organs were characterized
      microbiologically by culture. Bacterial colonies were identified by a
      desorption/ionization time-of-flight mass spectrometry system (MALDI TOF/TOF).
      RESULTS: The histological study of the skin lesions revealed serious acanthosis,
      hyperkeratosis, rete ridges, spongiotic oedema, serocellular and eosinophilic
      crusts, exocytosis foci, apoptotic cells and sebaceous gland hyperplasia. The
      cellular response in the dermis was consistent with type I and type IV
      hypersensitivity responses. The most prominent histological findings in non
      dermal tissues were lymphoid hyperplasia, leukocytosis, congestion and the
      presence of amyloid deposits. The increase in serum concentrations of
      acetylcholinesterase and amyloid A protein correlated positively with the
      establishment of the inflammatory response in mangy skin and the presence of
      systemic amyloidosis. A wide variety of bacterial agents were isolated and the
      simultaneous presence of these in mangy skin, lymph nodes and internal organs
      such as lungs, liver, spleen and kidney was compatible with a septicaemic pattern
      of infection. CONCLUSIONS: The alteration of biomarkers of inflammation and its
      implication in the pathogenesis of the disease and development of lesions in non
      dermal tissues and septicaemic processes are serious conditioners for the
      survival of the mangy ibex. This severe clinical picture could be an important
      factor when considering the decision to eliminate animals that exceed a certain
      disease threshold from a population.

PMID- 29202803
TI  - Emerging mechanisms and novel targets in allergic inflammation and asthma.
AB  - Airway inflammation is key to the severity and persistence of asthma. Recent
      studies have revealed novel immune mechanisms that target dendritic cells, T
      helper 2 cytokines, regulatory T cells, and type 2 innate lymphoid cells in
      allergic inflammation, as well as novel approaches that target airway smooth
      muscle in asthma. These advances inform the development of new targeted
      treatments for allergic inflammation and asthma with the potential to provide
      therapeutic benefit.

PMID- 29202804
TI  - Prevalence and determinants of differences in cystatin C and creatinine-based
      estimated glomerular filtration rate in community-dwelling older adults: a cross
      sectional study.
AB  - BACKGROUND: Differences in cystatin C and creatinine-based estimated glomerular
      filtration rate (eGFR) can lead to clinical uncertainty. Existing eGFR equations
      perform poorly in a subset of individuals. This study aims to describe the
      prevalence of differences between cystatin C-based (eGFRcys) and creatinine-based
      (eGFRcreat) eGFR in older adults and to explore which subsets of individuals may
      be most affected by differing estimations. METHODS: In this cross-sectional
      study, participants from a cohort of community-dwelling older adults were
      examined at a baseline visit in 2001-2004 as part of the larger "Good Aging in
      Skane" study. Exposure variables were obtained from questionnaires, interviews,
      examinations, and medical records. Blood samples were taken during the baseline
      visit, cryopreserved, and analyzed at a later time for biomarkers. The CKD-EPI
      equations were used to estimate GFR. Initial descriptive analyses were performed
      on 2931 individuals. A total of 2532 participants were included in the final
      multiple linear regression. RESULTS: Nearly two-thirds of participants had eGFR
      differences exceeding 10%, with nearly 20 % of participants having eGFR
      differences exceeding 30%. Smoking, age, body mass index (BMI), C-reactive
      protein (CRP), glucocorticoid use, and mean eGFR were correlated with differences
      between eGFRcreat and eGFRcys. CONCLUSIONS: Differences between eGFRcreat and
      eGFRcys are common and often of large magnitude in this community-dwelling
      population of older adults. The finding of multiple non-GFR determinants
      correlated to differences in GFR estimations can help direct future research to
      improve eGFR equations for subgroups prone to conflicting GFR estimations or to
      guide choice of biomarker for GFR estimation in these subgroups.

PMID- 29202805
TI  - Clinical significance of PCDH10 promoter methylation in diffuse large B-cell
      lymphoma.
AB  - BACKGROUND: PCDH10, one of the non-clustered protocadherins, is identified as a
      tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10
      was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes,
      suggesting that its epigenetic aberrance is essential to the lymphomagenesis.
      However, there are few studies on the clinicopathological relevance and
      prognostic significance of PCDH10 methylation status in DLBCL. METHODS: One
      hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to
      extract genomic DNA and perform bisulfite modification. Their methylation status
      of PCDH10 promoter were accessed by methylation-specific PCR (MSP) with
      methylated and unmethylated primers. Analysis of overall survival and
      clinicopathological correlation were conducted. RESULTS: PCDH10 hypermethylation
      were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive
      lymph node/follicular hyperplasia. In RCHOP-treated cohort, promoter methylation
      of PCDH10 is an independent prognostic indicator of worse overall survival (p =
      0.017; HR 4.045; 95%CI 1.287-12.711) and worse progress-free survival (p = 0.014;
      HR 2.977; 95%CI 1.245-7.119). Whereas, PCDH10 hypermethylation wasn't correlated
      with MYC translocation and cell of origin classification using Hans model.
      CONCLUSIONS: PCDH10 methylation status could serve as a valuable biomarker for
      risk classification, and a potential therapeutic target for demethylating drugs
      in DLBCL in the future.

PMID- 29202806
TI  - Risk factors for joint replacement in knee osteoarthritis; a 15-year follow-up
      study.
AB  - BACKGROUND: To evaluate whether clinical, radiographic or MRI findings are
      associated with long term risk for total knee arthroplasty (TKA) in persons with
      knee osteoarthritis. METHODS: We performed a follow-up analysis of 100 persons
      with knee osteoarthritis who participated in a clinical trial between 2000 and
      2002. Clinical data as well as radiography and MRI of the inclusion knee were
      obtained in all participants. Data on TKA procedures were extracted from The
      Danish National Patient Register. Clinical, radiographic and MRI findings were
      analyzed for associations with subsequent TKA. RESULTS: During a mean follow-up
      period of 15 years, 66% received a TKA in the included knee (target knee); 37%
      also received a TKA in the other knee. The degree of joint space narrowing was
      highly associated with subsequent TKA (adjusted odds ratio (OR) 5.0 (95%
      confidence interval (95% CI) 2.6 - 9.9)) as was a radiological sum score
      comprising joint space narrowing, osteophytes, subchondral sclerosis and cysts
      (adjusted OR 1.7 (95% CI 1.3 - 2.1)). MRI detected bone marrow lesions, synovitis
      and effusion were similarly associated with subsequent TKA with an adjusted OR of
      2.3 (95% CI 1.3 - 4.0), 2.8 (95% CI 1.5 - 5.2) and 1.9 (95% CI 1.2 - 3.1),
      respectively. Increased body mass index (BMI) was not associated with subsequent
      TKA in the target knee but was associated with TKA in the other knee (OR 2.3 (95%
      CI 1.2 - 4.3). CONCLUSIONS: Radiographic findings including joint space narrowing
      and MRI detected bone marrow lesions, synovitis and effusion were all
      significantly associated with the long term risk of TKA in persons with knee
      osteoarthritis.

PMID- 29202807
TI  - Granatum: a graphical single-cell RNA-Seq analysis pipeline for genomics
      scientists.
AB  - BACKGROUND: Single-cell RNA sequencing (scRNA-Seq) is an increasingly popular
      platform to study heterogeneity at the single-cell level. Computational methods
      to process scRNA-Seq data are not very accessible to bench scientists as they
      require a significant amount of bioinformatic skills. RESULTS: We have developed
      Granatum, a web-based scRNA-Seq analysis pipeline to make analysis more broadly
      accessible to researchers. Without a single line of programming code, users can
      click through the pipeline, setting parameters and visualizing results via the
      interactive graphical interface. Granatum conveniently walks users through
      various steps of scRNA-Seq analysis. It has a comprehensive list of modules,
      including plate merging and batch-effect removal, outlier-sample removal, gene
      expression normalization, imputation, gene filtering, cell clustering,
      differential gene expression analysis, pathway/ontology enrichment analysis,
      protein network interaction visualization, and pseudo-time cell series
      construction. CONCLUSIONS: Granatum enables broad adoption of scRNA-Seq
      technology by empowering bench scientists with an easy-to-use graphical interface
      for scRNA-Seq data analysis. The package is freely available for research use at
      http://garmiregroup.org/granatum/app.

PMID- 29202808
TI  - Group cognitive behavioural therapy with compassion training for depression in a
      Japanese community: a single-group feasibility study.
AB  - OBJECTIVE: Depression is a representative mental problem, and more than 350
      million people are suffering in the world. Cognitive behavioural therapy (CBT) in
      individual or group formats is mainly recommended in major guidelines. However,
      patients with high self-criticism have a poor response to CBT. To treat such
      patients, psychotherapies focusing on compassion are gaining attention. Although
      trials have begun to be reported, there are relatively few studies examining the
      effectiveness of group CBT with compassion work for managing depression. The
      purpose of this study was to evaluate the feasibility and acceptability and the
      estimate effect size of group CBT with compassion training for future controlled
      studies. RESULTS: Fourteen participants were enrolled in the trial, of which 13
      completed the intervention, and 12 completed a 6-month follow-up assessment.
      Participants received a 1 h group-based CBT with compassion training session
      every week for 10 weeks. The effect of the intervention on participants' Beck
      Depression Inventory score was examined using a general linear mixed model. This
      analysis showed an effect size of d = 1.12 at post intervention and d = 0.92 at 6
      month follow-up. Group cognitive behavioural therapy with compassion training for
      depression shows feasibility and acceptability in a Japanese community. Trial
      Registration UMIN000015007.

PMID- 29202809
TI  - Five years' follow-up of dental fear and anxiety, experience of dental care and
      oral health behaviour in Swedish preterm and full-term adolescents.
AB  - BACKGROUND: There is rising concern about how preterm birth affects long-term
      health later in life. The various effects that preterm birth have on
      developmental outcomes, cognitive profiles and medical health may also affect
      levels of cooperation in the dental care situation in addition to general oral
      health and other oral health-related habits. Oral health is an integral part of
      one's general health and well-being; however, less is known about how prematurity
      affects oral health and other related areas such as dental care, and including
      dental fear and anxiety (DFA) in individuals during adolescence and adulthood.
      This is considered of special interest to study, as preterm children during the
      preschool and school period were reported to have behavioural problems during
      dental treatments and less than favourable oral hygiene. METHODS: A questionnaire
      was used of self-report design and structured into behavioural aspects relating
      to dental treatment, oral health-related factors, and medical health. This
      questionnaire at 17-19 years of age was a follow-up from 12 to 14 years of age
      and considered a predictor for planning future dental care for this group of
      patients. The 145 participating adolescents were all preterm, born between 23 and
      32 weeks of gestation and 140 full-term controls, born >=37 weeks of gestation.
      RESULTS: Dental fear and anxiety, oral health behaviour, and intake of sweets and
      sugary drinks of 17-19-year old adolescents born preterm was comparable to that
      of the full-term control group. Medical health problems as well as the intake of
      sweets and sugary drinks increased from the time of early adolescence to late
      adolescence in both groups. CONCLUSIONS: Preterm as well as full-term adolescents
      between 17 and 19 years of age are satisfied with their dental care and display
      low prevalence of dental fear and anxiety (DFA). The findings in this study
      indicate that adolescents born very preterm and extremely preterm are well
      prepared for transition to dental care in adult life with expectations of being
      able to take responsibility for their oral health.

PMID- 29202810
TI  - Trajectories of body mass index among Canadian seniors and associated mortality
      risk.
AB  - BACKGROUND: This study aims to characterize the heterogeneity in BMI trajectories
      and evaluate how different BMI trajectories predict mortality risk in Canadian
      seniors. METHODS: Data came from the Canadian National Population Health Survey
      (NPHS, 1994-2011) and 1480 individuals aged 65-79 years with at least four BMI
      records were included in this study. Group-based trajectory model was used to
      identify distinct subgroups of longitudinal trajectories of BMI measured over 19
      years for men and women. Cox proportional hazards models were used to examine the
      association between BMI trajectories and mortality risks. RESULTS: Distinct
      trajectory patterns were found for men and women: 'Normal Weight-Down'(N-D),
      'Overweight-Normal weight' (OV-N), 'Obese I-Down' (OB I-D), and 'Obese II- Down'
      (OB II-D) for women; and 'Normal Weight-Down' (N-D), 'Overweight-Normal weight'
      (OV-N), 'Overweight-Stable' (OV-S), and 'Obese-Stable' (OB-S) for men. Comparing
      with OV-N, men in the OV-S group had the lowest mortality risk followed by the N
      D (HR = 1.66) and OB-S (HR = 1.98) groups, after adjusting for covariates.
      Compared with OV-N, women in the OB II-D group with three or more chronic health
      conditions had higher mortality risk (HR = 1.61); however, women in OB II-D had
      lower risk (HR = 0.56) if they had less than three conditions. CONCLUSION: The
      course of BMI over time in Canadian seniors appears to follow one of four
      different patterns depending on gender. The findings suggest that men who were
      overweight at age 65 and lost weight over time had the lowest mortality risk.
      Interestingly, obese women with decreasing BMI have different mortality risks,
      depending on their chronic health conditions. The findings provide new insights
      concerning the associations between BMI and mortality risk.

PMID- 29202811
TI  - High prevalence of prescription of psychotropic drugs for older patients in a
      general hospital.
AB  - BACKGROUND: Many elderly patients receive psychotropic drugs. Treatment with
      psychotropic agents is associated with serious side effects including an
      increased risk of falls and fractures. Several psychotropic drugs are considered
      potentially inappropriate for treatment of the elderly. METHODS: A retrospective
      chart review was conducted covering all patients aged >= 65 years who were
      admitted to Evangelisches Krankenhaus Gottingen-Weende between 01/01/2013 and
      03/31/2013. Psychotropic drugs reviewed for included benzodiazepines, Z-drugs,
      antidepressants and neuroleptics, but not drugs for sedation during artificial
      ventilation or pre-medication before surgery. Potentially inappropriate drugs
      were identified according to the PRISCUS list. To assess which factors were
      associated with the administration of psychotropic drugs, univariate and
      multivariable logistic regression analyses were performed. RESULTS: The charts of
      2130 patients (1231 women) were analyzed. 53.9% of all patients received at least
      one psychotropic medication (29.5% benzodiazepines, 12.6% Z-drugs, 22.2%
      antidepressants, 11.9% neuroleptics). The mean number of psychotropic drugs
      prescribed per patient with at least one prescription was 1.6. Patients treated
      in the geriatric department most often received antidepressants (45.0%),
      neuroleptics (20.6%) and Z-drugs (27.5%). Benzodiazepines and Z-drugs were
      prescribed mostly as medication on demand (77.7% of benzodiazepines, 73.9% of Z
      drugs). Surgical patients most frequently received benzodiazepines (37.1%).
      Nearly one-third of all patients >= 65 years was treated with at least one
      potentially inappropriate psychotropic medication. The mean number of potentially
      inappropriate psychotropic medications per patient with at least one psychotropic
      prescription was 0.69. The percentage of patients with potentially inappropriate
      psychotropic medication was highest in the surgical departments (74.1%). Female
      gender (adjusted OR 1.36; 95% CI 1.14 to 1.63), stay in the Department of
      Geriatrics (2.69; 2.01 to 3.60) or the interdisciplinary intensive care unit
      (1.87; 1.33 to 2.64) and age >= 85 years (1.33; 1.10 to 1.60) were associated
      with psychotropic drug treatment. CONCLUSIONS: A high percentage of patients aged
      >= 65 years received psychotropic drugs. The chance that a potentially
      inappropriate psychotropic drug would be administered was highest in the surgical
      departments. Antidepressants, neuroleptics and Z-drugs were used surprisingly
      often in geriatric medicine. Educational strategies could reduce the use of
      psychotropic drugs and the prescription of potentially inappropriate medications.

PMID- 29202812
TI  - Celastrol improves self-renewal and differentiation of human tendon-derived stem
      cells by suppressing Smad7 through hypoxia.
AB  - BACKGROUND: We aimed to evaluate the potential enhancing effect of celastrol on
      the stemness of human tendon-derived stem cells (hTSCs) in vitro and the
      underlying molecular mechanisms. METHODS: The capability of hTSC self-renewal was
      assessed by cell proliferation and colony formation as determined with the CCK-8
      kit. Adipogenesis, chondrogenesis, and osteogenesis were determined by Oil Red O,
      Alcian Blue, and Alizarin Red staining, respectively. The relative mRNA levels of
      Sox9, PPARgamma, Runx2, Smad7, and HIF1alpha were determined by real-time
      polymerase chain reaction (PCR). The levels of Smad7 and HIF1alpha protein were
      measured by immunoblotting. The chromatin immunoprecipitation (ChIP) assay was
      used to assess the direct binding of HIF1alpha to the Smad7 promoter. Suppression
      of Smad7 induced by hypoxia was examined using the luciferase reporter assay.
      RESULTS: We found that treatment with celastrol resulted in improvement in both
      the multi-differentiation potential and self-renewal capability of hTSCs.
      Celastrol elicited hypoxia and subsequently suppressed the expression of Smad7
      through direct association with the hypoxia response element consensus sequence.
      Further, we demonstrated that both Smad7 and HIF1alpha were involved in the
      beneficial effects of celastrol on the differentiation and self-renewal of hTSCs.
      CONCLUSIONS: We demonstrated the positive effect of celastrol on the stemness of
      hTSCs and elucidated the essential role of the HIF1alpha-Smad7 pathway in this
      process.

PMID- 29202813
TI  - A predominance of hypertensive heart disease among patients with cardiac disease
      in Buea, a semi-urban setting, South West Region of Cameroon.
AB  - OBJECTIVE: The pattern of heart disease is diverse within and among world
      regions. The little data on the spectrum of heart disease in Cameroon has been so
      far limited to major cities. We sought to describe the pattern of heart disease
      in Buea, the South West Region of Cameroon, a semi-urban setting. This was a
      descriptive cross-sectional study. Between June 2016 and April 2017 the
      echocardiography register of the Buea Regional Hospital was surveyed. We
      extracted data on the age, sex and echocardiographic diagnosis. RESULTS: Out of
      529 patients who underwent echocardiography, 239 (45.2%) had a definite heart
      disease. There were 137 (57.3%) females. The mean age was 58 years (range 3-94
      years). The most common echocardiographic diagnoses were hypertensive heart
      disease (43.2%), dilated cardiomyopathies (17.6%), ischemic heart diseases
      (9.6%), and cor pulmonale (8.8%). Rheumatic heart disease affected 6.7% of the
      patients. The most common rheumatic heart disease was mitral stenosis followed by
      mitral regurgitation. Congenital heart disease represented 2.1% and 5 patients
      (2.1%) had pulmonary hypertension. Hypertensive heart disease is the most common
      cardiac disease in this semi-urban region in Cameroon. Rheumatic heart disease
      still affects a sizable proportion of patients. Prevention of cardiac disease in
      our setting should focus on mass screening, the treatment and control of
      hypertension.

PMID- 29202814
TI  - Occurrence of spontaneous bilateral tubal pregnancy in a low-income setting in
      rural Cameroon: a case report.
AB  - BACKGROUND: Ectopic pregnancy is a life-threatening emergency warranting
      immediate recognition and prompt intervention. Bilateral tubal pregnancy is the
      rarest form of ectopic pregnancy with very limited data on its occurrence
      reported in sub-Saharan Africa. CASE PRESENTATION: We report the case of a 40
      year-old multigravida with chief complains of lower abdominal pain evolving for 5
      days in whom an intraoperative diagnosis of spontaneous bilateral tubal pregnancy
      (plus ruptured right tube) was made. CONCLUSIONS: Ectopic pregnancy is one of the
      major causes of maternal mortality in sub-Saharan Africa. Thus, clinicians should
      maintain a high index of suspicion, even in the absence of hallmark features and
      thorough clinical examination undertaken especially in resource-limited settings.
      Examination of both tubes at laparotomy for ectopic pregnancy should be routine
      and mandatory.

PMID- 29202815
TI  - Normothermia after decompressive surgery for space-occupying middle cerebral
      artery infarction: a protocol-based approach.
AB  - BACKGROUND: Moderate hypothermia after decompressive surgery might not be
      beneficial for stroke patients. However, normothermia may prove to be an
      effective method of enhancing neurological outcomes. The study aims were to
      evaluate the application of a pre-specified normothermia protocol in stroke
      patients after decompressive surgery and its impact on temperature load, and to
      describe the functional outcome of patients at 12 months after treatment.
      METHODS: We analysed patients with space-occupying middle cerebral artery (MCA)
      infarction treated with decompressive surgery and a pre-specified temperature
      management protocol. Patients treated primarily with device-controlled
      normothermia or hypothermia were excluded. The individual temperature load above
      36.5  degrees C was calculated for the first 96 h after hemicraniectomy as the
      Area Under the Curve, using  degrees C x hours. The effect of temperature load on
      functional outcome at 12 months was analysed by logistic regression. RESULTS: We
      included 40 stroke patients treated with decompressive surgery (mean [SD] age:
      58.9 [10.1] years; mean [SD] time to surgery: 30.5 [16.7] hours). Fever
      (temperature > 37.5  degrees C) developed in 26 patients during the first 96 h
      after surgery and mean (SD) temperature load above 36.5  degrees C in this time
      period was 62,3 (+/- 47,6)  degrees C*hours. At one year after stroke onset, a
      moderate to moderately severe disability (modified Rankin Scale score of 3 or 4)
      was observed in 32% of patients, and a severe disability (score of 5) in 37% of
      patients, respectively. The lethality in the cohort at 12 months was 32%. The
      temperature load during the first 96 h was not an independent predictor for 12
      month lethality (OR 0.986 [95%-CI:0.967-1.002]; p < 0.12). CONCLUSIONS:
      Temperature control in surgically treated patients with space-occupying MCA
      infarction using a pre-specified protocol excluding temperature management
      systems resulted in mild hyperthermia between 36.8  degrees C and 37.2  degrees C
      and a low overall temperature load. Future prospective studies on larger cohorts
      comparing different strategies for normothermia treatment including temperature
      management devices are needed.

PMID- 29202816
TI  - The treatment of migraine patients within chiropractic: analysis of a nationally
      representative survey of 1869 chiropractors.
AB  - BACKGROUND: While the clinical role of manual therapies in migraine management is
      unclear, the use of chiropractors for this condition is considerable. The aim of
      this study is to evaluate the prevalence and characteristics of chiropractors who
      frequently manage patients with migraine. METHODS: A national cross-sectional
      survey of chiropractors collected information on practitioner characteristics,
      clinical management characteristics and practice settings. A secondary analysis
      was conducted on 1869 respondents who reported on their migraine caseload to
      determine the predictors associated with the frequent management of patients with
      migraine. RESULTS: A large proportion of chiropractors report having a high
      migraine caseload (HMC) (n = 990; 53.0%). The strongest factors predicting a
      chiropractor having a HMC include the frequent treatment of patients with axial
      neck pain (OR = 2.89; 95%CI: 1.18, 7.07), thoracic pain (referred/radicular) (OR
      = 2.52; 95%CI: 1.58, 3.21) and non-musculoskeletal disorders (OR = 3.06; 95%CI:
      2.13, 4.39). CONCLUSIONS: Several practice-setting and clinical management
      characteristics are associated with chiropractors managing a HMC. These findings
      raise key questions about the therapeutic approach to chiropractic migraine
      management that deserves further examination. There is a need for more primary
      research to assess the approach to headache and migraine management provided by
      chiropractors and to understand the prevalence, burden and comorbidities
      associated with migraine found within chiropractic patient populations. This
      information is vital in helping to inform safe, effective and coordinated care
      for migraine sufferers within the wider health system.

PMID- 29202817
TI  - Use of cardiovascular magnetic resonance in the evaluation of a giant right
      atrial appendage aneurysm: a case report and review of the literature.
AB  - BACKGROUND: Right atrial appendage aneurysms are rare entities that may have
      significant clinical consequences. When co-existing with atrial fibrillation,
      patients are at risk of developing pulmonary or paradoxical systemic emboli. CASE
      PRESENTATION: An elderly patient presented to medical attention with symptoms of
      acute diverticulitis. On abdominal computed tomography, a massively enlarged
      right atrial appendage aneurysm was discovered incidentally. The aneurysm caused
      marked compression of the right ventricle and contained an area of
      hypoenhancement concerning for an intraluminal thrombus. Gadolinium-enhanced
      cardiovascular magnetic resonance was performed and first-pass perfusion images
      demonstrated that the area of hypoenhancement was in fact poorly mixing blood.
      The patient was therefore managed medically. CONCLUSION: Right atrial appendage
      aneurysms are infrequently encountered cardiac abnormalities. In the literature,
      surgery has been offered to patients who are young, symptomatic, or have evidence
      of thrombotic disease, although whether this practice pattern is associated with
      superior clinical outcomes is unclear. In the present case, gadolinium-enhanced
      cardiovascular magnetic resonance imaging was used to exclude the presence of
      intraluminal thrombus in an elderly patient, which helped orient the patient's
      treating team towards medical-rather than surgical-therapy.

PMID- 29202818
TI  - The development of a nursing subset of patient problems to support
      interoperability.
AB  - BACKGROUND: Since the emergence of electronic health records, nursing information
      is increasingly being recorded and stored digitally. Several studies have shown
      that a wide range of nursing information is not interoperable and cannot be re
      used in different health contexts. Difficulties arise when nurses share
      information with others involved in the delivery of nursing care. The aim of this
      study is to develop a nursing subset of patient problems that are prevalent in
      nursing practice, based on the SNOMED CT terminology to assist in the exchange
      and comparability of nursing information. METHODS: Explorative qualitative focus
      groups were used to collect data. Mixed focus groups were defined. Additionally,
      a nursing researcher and a nursing expert with knowledge of terminologies and a
      terminologist participated in each focus group. The participants, who work in a
      range of practical contexts, discussed and reviewed patient problems from various
      perspectives. RESULTS: Sixty-seven participants divided over seven focus groups
      selected and defined 119 patient problems. Each patient problem could be
      documented and coded with a current status or an at-risk status. Sixty-six
      percent of the patient problems included are covered by the definitions
      established by the International Classification of Nursing Practice, the
      reference terminology for nursing practice. For the remainder, definitions from
      either an official national guideline or a classification were used. Each of the
      119 patient problems has a unique SNOMED CT identifier. CONCLUSIONS: To support
      the interoperability of nursing information, a national nursing subset of patient
      problems based on a terminology (SNOMED CT) has been developed. Using
      unambiguously defined patient problems is beneficial for clinical nursing
      practice, because nurses can then compare and exchange information from different
      settings. A key strength of this study is that nurses were extensively involved
      in the development process. Further research is required to link or associate
      nursing patient problems to concepts from a nursing classification with the same
      meaning.

PMID- 29202819
TI  - Guidance by physicians and pharmacists during antidepressant therapy: patients'
      needs and suggestions for improvement.
AB  - BACKGROUND: Guidance of patients treated with antidepressants is paramount for
      successful therapy. The aim was to assess patients' needs and suggestions for
      improvement of guidance by physicians and pharmacists during second generation
      antidepressant (SGA) therapy. METHODS: Five focus group discussions were held
      with a total of 34 patients using an SGA. The discussions were conducted flexibly
      and responsively using a semi-structured topic list. All focus group discussions
      were video-recorded and transcripts were analyzed using ATLAS.ti for coding,
      thematic and open analysis. RESULTS: Participants stated they were in need of
      better guidance. They suggested improving content of information during
      decisional moments, patient-health care professional communication and
      communication between health care professionals, and finally, organization of
      guidance. Barriers to achieving improved guidance were cited. CONCLUSIONS:
      Content, communication and organization of guidance are pivotal for achieving
      optimal guidance. Participants mentioned their current experienced guidance had
      limitations and brought up solutions for improvement. A next step would be to
      discuss the suggested solutions with health care professionals to assess their
      views and to discuss the possibility for implementation. After implementation,
      future studies could be aimed at determination of its impact on patients'
      treatment efficacy, quality of life, treatment satisfaction and healthcare costs.

PMID- 29202820
TI  - Hand-assisted laparoscopic surgery versus laparoscopic right colectomy: a meta
      analysis.
AB  - OBJECTIVE: The objective of this study is to systematically assess the clinical
      efficacy of hand-assisted laparoscopic surgery (HALS) and laparoscopic right
      colectomy (LRC). METHODS: The randomized controlled trials (RCTs) and non-RCTs
      were collected by searching electronic databases (Pubmed, Embase, and the
      Cochrane Library). The outcomes included intraoperative outcomes, postoperative
      outcomes, postoperative morbidity, and oncologic outcomes. Meta-analysis was
      performed using of RevMan 5.3 software. RESULTS: A total of five studies
      involving 438 patients were finally included, with 202 cases in HALS group and
      236 cases in LRC group. Results of meta-analysis showed that there was no
      statistical difference between HALS and LRC in terms of conversion rate, length
      of hospital stay, reoperation rate, postoperative morbidity, and oncologic
      outcomes. The operative time was 6.5 min shorter in HALS group; however, it was
      not a clinically significant difference. Although the incision length was longer
      in HALS, it did not influence the postoperative recovery. CONCLUSIONS: HALS can
      be considered an alternative to LRC which combines the advantages of open as well
      as laparoscopic surgery.

PMID- 29202821
TI  - Effects of treatment changes on asthma phenotype prevalence and airway neutrophil
      function.
AB  - BACKGROUND: Asthma inflammatory phenotypes are often defined by relative cell
      counts of airway eosinophils/neutrophils. However, the importance of neutrophilia
      remains unclear, as does the effect of ICS treatment on asthma phenotypes and
      airway neutrophil function. The purpose of this study was to assess asthma
      phenotype prevalence/characteristics in a community setting, and, in a nested
      preliminary study, determine how treatment changes affect phenotype stability and
      inflammation, with particular focus on airway neutrophils. METHODS: Fifty adult
      asthmatics and 39 non-asthmatics were assessed using questionnaires, skin prick
      tests, spirometry, exhaled nitric oxide (FENO) measurement, and sputum induction.
      Twenty-one asthmatics underwent further assessment following treatment
      optimisation (n = 11) or sub-optimisation (n = 10). RESULTS: Forty percent
      (20/50) had eosinophilic asthma (EA) and 8% had neutrophilic asthma. EA was
      associated with increased FENO, bronchodilator reversibility (BDR) and reduced
      lung function (p < 0.05). Following optimisation/sub-optimisation, the EA/NEA
      (non-eosinophilic asthma) phenotype changed in 11/21 (52%) asthmatics. In
      particular, fewer subjects had EA post treatment optimisation, but this was not
      statistically significant. However, a significant (p < 0.05) reduction in FENO,
      ACQ7 score, and BDR was observed after treatment optimisation, as well as an
      increase in FEV1-% predicted (p < 0.05). It was also associated with reduced
      eosinophils (p < 0.05) and enhanced neutrophil phagocytosis (p < 0.05) in EA
      only, and enhanced neutrophil oxidative burst in both EA and NEA (p < 0.05).
      CONCLUSIONS: In this community based population, non-eosinophilic asthma was
      common, less severe than EA, and at baseline most asthmatics showed no evidence
      of inflammation. In the nested change in treatment study, treatment optimisation
      was associated with reduced sputum eosinophils, improved symptoms and lung
      function, and enhanced neutrophil function, but a significant reduction in EA
      could not be demonstrated. TRIAL REGISTRATION: The nested change in treatment
      component of this study is registered at the Australia and New Zealand Clinical
      Trial Registry ( www.ANZCTR.org.au ) ACTRN12617001356358 . Registration date
      27/09/2017. Retrospectively registered.

PMID- 29202822
TI  - The p75NTR-mediated effect of nerve growth factor in L6C5 myogenic cells.
AB  - OBJECTIVE: During muscle development or regeneration, myocytes produce nerve
      growth factor (NGF) as well as its tyrosine-kinase and p75-neurotrophin (p75NTR)
      receptors. It has been published that the p75NTR receptor could represent a key
      regulator of NGF-mediated myoprotective effect on satellite cells, but the
      precise function of NGF/p75 signaling pathway on myogenic cell proliferation,
      survival and differentiation remains fragmented and controversial. Here, we
      verified the role of NGF in the growth, survival and differentiation of p75NTR
      expressing L6C5 myogenic cells, specifically inquiring for the putative
      involvement of the nuclear factor kappaB (NFkappaB) and the small heat shock
      proteins (sHSPs) alphaB-crystallin and Hsp27 in these processes. RESULTS:
      Although NGF was not effective in modulating myogenic cell growth or survival in
      both standard or stress conditions, we demonstrated for the first time that,
      under serum deprivation, NGF sustained the activity of some key enzymes involved
      in energy metabolism. Moreover, we confirmed that NGF promotes myogenic fusion
      and expression of the structural protein myosin heavy chain while modulating
      NFkappaB activation and the content of sHSPs correlated with the differentiation
      process. We conclude that p75NTR is sufficient to mediate the modulation of L6C5
      myogenic differentiation by NGF in term of structural, metabolic and functional
      changes.

PMID- 29202823
TI  - Trastuzumab emtansine delays and overcomes resistance to the third-generation
      EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines.
AB  - BACKGROUND: Osimertinib is a third-generation EGFR-TKI with a high selective
      potency against T790M-mutant NSCLC patients. Considering that osimertinib can
      lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a
      mechanism of resistance to osimertinib, this study was addressed to investigate
      the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in
      order to improve the efficacy of osimertinib and delay or overcome resistance in
      NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2
      amplification. METHODS: The effects of osimertinib combined with T-DM1 on cell
      proliferation, cell cycle, cell death, antibody-dependent cell-mediated
      cytotoxicity (ADCC), and acquisition of osimertinib resistance was investigated
      in PC9, PC9-T790M and H1975 cell lines. The potential of overcoming osimertinib
      resistance with T-DM1 was tested in a PC9/HER2c1 xenograft model. RESULTS: T-DM1
      exerted an additive effect when combined with osimertinib in terms of inhibition
      of cell proliferation, cell death and ADCC induction in PC9, PC9-T790M and H1975
      cell lines. Combining osimertinib and T-DM1 using different schedules in long
      term growth experiments revealed that the appearance of osimertinib-resistance
      was prevented in PC9-T790M and delayed in H1975 cells when the two drugs were
      given together. By contrast, when osimertinib was followed by T-DM1 an
      antagonistic effect was observed on cell proliferation, cell death and resistance
      acquisition. In xenograft models, we demonstrated that HER-2 amplification was
      associated with osimertinib-resistance and that T-DM1 co-administration is a
      potential strategy to overcome this resistance. CONCLUSIONS: Our data suggest
      that concomitant treatment with osimertinib and T-DM1 may be a promising
      therapeutic strategy for EGFR-mutant NSCLC.

PMID- 29202824
TI  - Cathodal transcranial direct-current stimulation over right posterior parietal
      cortex enhances human temporal discrimination ability.
AB  - BACKGROUND: Time perception associated with durations from 1 s to several minutes
      involves activity in the right posterior parietal cortex (rPPC). It is unclear
      whether altering the activity of the rPPC affects an individual's timing
      performance. Here, we investigated the human timing performance under the
      application of transcranial direct-current stimulation (tDCS) that altered the
      neural activities of the rPPC. METHODS: We measured the participants' duration
      discrimination threshold by administering a behavioral task during the tDCS
      application. The tDCS conditions consisted of anodal, cathodal, and sham
      conditions. The electrodes were placed over the P4 position (10-20 system) and on
      the left supraorbital forehead. On each task trial, the participant observed two
      visual stimuli and indicated which was longer. The amount of difference between
      the two stimulus durations was varied repeatedly throughout the trials according
      to the participant's responses. The correct answer rate of the trials was
      calculated for each amount of difference, and the minimum amount with the correct
      answer rate exceeding 75% was selected as the threshold. The data were analyzed
      by a linear mixed-effects models procedure. RESULTS: Nineteen volunteers
      participated in the experiment. We excluded three participants from the analysis:
      two who reported extreme sleepiness while performing the task and one who could
      recognize the sham condition correctly with confidence. Our analysis of the 16
      participants' data showed that the average value of the thresholds observed under
      the cathodal condition was lower than that of the sham condition. This suggests
      that inhibition of the rPPC leads to an improvement in temporal discrimination
      performance, resulting in improved timing performance. CONCLUSIONS: In the
      present study, we found a new effect that cathodal tDCS over the rPPC enhances
      temporal discrimination performance. In terms of the existence of anodal/cathodal
      tDCS effects on human timing performance, the results were consistent with a
      previous study that investigated temporal reproduction performance during tDCS
      application. However, the results of the current study further indicated that
      cathodal tDCS over the rPPC increases accuracy of observed time duration rather
      than inducing an overestimation as a previous study reported.

PMID- 29202825
TI  - Antibacterial activity and effects of Colla corii asini on Salmonella typhimurium
      invasion in vitro and in vivo.
AB  - BACKGROUND: Salmonella enterica serovar Typhimurium is a foodborne pathogen that
      triggers inflammatory responses in the intestines of humans and livestock. Colla
      corii asini is a traditional medicine used to treat gynecologic and chronic
      diseases in Korea and China. However, the antibacterial activity of Colla corii
      asini has been unknown. In this study, we investigated the antibacterial activity
      and effects of Colla corii asini extract on Salmonella typhimurium invasion.
      METHODS: To tested for antibacterial effects of Colla corii asini extracts, we
      confirmed the agar diffusion using Luria solid broth medium. Also, we determined
      the MIC (minimum inhibitory concentration) and the MBC (minimum bactericidal
      concentration) value of the Colla corii asini ethanol extract (CEE) by using two
      fold serial dilution methods. We evaluated the expression of salmonella invasion
      proteins including SipA, SipB and SipC by using Western blot and qPCR at the
      concentration of CEE without inhibition of bacterial growth. In vitro and vivo,
      we determined the inhibitory effect of invasion of S. typhimurium on CEE by using
      gentamicin assay and S. typhimurium-infected mice. RESULTS: CEE significantly
      inhibited the growth of Salmonella typhimurium in an agar diffuse assay and had
      an MIC of 0.78 mg/ml and an MBC of 1.56 mg/ml. Additionally, CEE reduced
      Salmonella typhimurium cell invasion via the inhibition of Salmonella typhimurium
      invasion proteins, such as SipA, SipB and SipC. Furthermore, CEE significantly
      suppressed invasion in the small intestines (ilea) of mice injected with
      Salmonella typhimurium. CONCLUSION: These findings show that Colla corii asini
      exerts antibacterial activity and suppresses Salmonella typhimurium invasion in
      vitro and in vivo. Together, these findings demonstrate that Colla corii asini is
      a potentially useful therapeutic herbal medicine for treating salmonella-mediated
      diseases.

PMID- 29202826
TI  - Autonomic nervous system involvement in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease
      characterized by increased pulmonary vascular resistance (PVR) leading to right
      ventricular (RV) failure. Autonomic nervous system involvement in the
      pathogenesis of PAH has been demonstrated several years ago, however the extent
      of this involvement is not fully understood. PAH is associated with increased
      sympathetic nervous system (SNS) activation, decreased heart rate variability,
      and presence of cardiac arrhythmias. There is also evidence for increased renin
      angiotensin-aldosterone system (RAAS) activation in PAH patients associated with
      clinical worsening. Reduction of neurohormonal activation could be an effective
      therapeutic strategy for PAH. Although therapies targeting adrenergic receptors
      or RAAS signaling pathways have been shown to reverse cardiac remodeling and
      improve outcomes in experimental pulmonary hypertension (PH)-models, the
      effectiveness and safety of such treatments in clinical settings have been
      uncertain. Recently, novel direct methods such as cervical ganglion block,
      pulmonary artery denervation (PADN), and renal denervation have been employed to
      attenuate SNS activation in PAH. In this review, we intend to summarize the
      multiple aspects of autonomic nervous system involvement in PAH and overview the
      different pharmacological and invasive strategies used to target autonomic
      nervous system for the treatment of PAH.

PMID- 29202827
TI  - Risk of disability pension in first and second generation immigrants: the role of
      age and region of birth in a prospective population-based study from Sweden.
AB  - BACKGROUND: In several countries, immigrants have higher disability pension (DP)
      rates than natives. Reasons for this are poorly understood. The aim of this study
      was to investigate if the risk of diagnosis-specific DP differed in first,
      second, and second/intermediate generation immigrants compared to natives, in
      general and across regions of birth, and stratified by age. METHODS: A population
      based prospective cohort study of all 3,507,055 individuals aged 19-50 years and
      living in Sweden in 2004 with a 6-year follow-up period. Hazard ratios (HR) and
      95% confidence intervals (CI) for mental and somatic DP were estimated by Cox
      regression for first, second, and second/intermediate generation immigrants
      compared to natives, across regions of birth and stratified by age. RESULTS:
      After multivariate adjustment, HRs for both mental and somatic DP were higher at
      follow-up in the first generation compared to natives: mental HR 1.17 (CI 1.12
      1.22) and somatic 1.15 (1.09-1.22) for individuals <35 years; 1.74 (1.69-1.79)
      and 1.70 (1.66-1.74) >=35 years (median), respectively. Immigrants born in Europe
      outside EU25, and countries outside Europe had particularly elevated HRs. Also in
      the second generation, HRs were higher in mental 1.29 (1.21-1.37) and somatic DP:
      1.30 (1.19-1.42) in those <35 years; and 1.18 (1.10-1.27); and 1.10 (1.03-1.17)
      for those >=35 years, respectively. Among second generation immigrants there were
      no strong differences in HRs between regions of birth. CONCLUSIONS: Compared to
      natives, the risk of DP was higher in first and second generation immigrants.
      Higher estimates were seen for immigrants from Europe outside EU25 and from the
      rest of the world in the first generation. No considerable differences in
      estimates regarding mental or somatic DP diagnoses were found.

PMID- 29202828
TI  - Calculation of the disease burden associated with environmental chemical
      exposures: application of toxicological information in health economic
      estimation.
AB  - Calculation of costs and the Burden of Disease (BoD) is useful in developing
      resource allocation and prioritization strategies in public and environmental
      health. While useful, the Disability-Adjusted Life Year (DALY) metric disregards
      subclinical dysfunctions, adheres to stringent causal criteria, and is hampered
      by gaps in environmental exposure data, especially from industrializing
      countries. For these reasons, a recently calculated environmental BoD of 5.18% of
      the total DALYs is likely underestimated. We combined and extended cost
      calculations for exposures to environmental chemicals, including neurotoxicants,
      air pollution, and endocrine disrupting chemicals, where sufficient data were
      available to determine dose-dependent adverse effects. Environmental exposure
      information allowed cost estimates for the U.S. and the EU, for OECD countries,
      though less comprehensive for industrializing countries. As a complement to these
      health economic estimations, we used attributable risk valuations from expert
      elicitations to as a third approach to assessing the environmental BoD. For
      comparison of the different estimates, we used country-specific monetary values
      of each DALY. The main limitation of DALY calculations is that they are available
      for few environmental chemicals and primarily based on mortality and impact and
      duration of clinical morbidity, while less serious conditions are mostly
      disregarded. Our economic estimates based on available exposure information and
      dose-response data on environmental risk factors need to be seen in conjunction
      with other assessments of the total cost for these environmental risk factors, as
      our estimate overlaps only slightly with the previously estimated environmental
      DALY costs and crude calculations relying on attributable risks for environmental
      risk factors. The three approaches complement one another and suggest that
      environmental chemical exposures contribute costs that may exceed 10% of the
      global domestic product and that current DALY calculations substantially
      underestimate the economic costs associated with preventable environmental risk
      factors. By including toxicological and epidemiological information and data on
      exposure distributions, more representative results can be obtained from
      utilizing health economic analyses of the adverse effects associated with
      environmental chemicals.

PMID- 29202829
TI  - Prevalence and risk factors of moderate to severe obstructive sleep apnea
      syndrome in major depression: a observational and retrospective study on 703
      subjects.
AB  - BACKGROUND: Several studies have investigated the prevalence and risk factors of
      depression in subjects with obstructive sleep apnea syndrome. However, few
      studies have investigated the prevalence and risk factors for obstructive sleep
      apnea syndrome in major depression. The aim of this study was to examine the
      prevalence and risk factors of moderate to severe obstructive sleep apnea
      syndrome in a large sample of individuals with major depression. METHODS: Data
      from 703 individuals with major depression recruited from the research database
      of the sleep laboratory of the Erasme Hospital were analysed. An apnea-hypopnea
      index of >=15 events per hour was used as cut-off score for moderate to severe
      obstructive sleep apnea syndrome. Logistic regression analyses were conducted to
      examine clinical and demographic risk factors of moderate to severe obstructive
      sleep apnea syndrome in major depression. RESULTS: The prevalence of moderate to
      severe obstructive sleep apnea syndrome in major depression is 13.94%.
      Multivariate logistic regression analysis revealed that male gender, snoring,
      excessive daytime sleepiness, lower insomnia complaint, presence of metabolic
      syndrome, age >= 50 years, BMI >30 kg/m2, ferritin >300 MUg/L, CRP >7 mg/L and
      duration of sleep >=8 h were significant risk factors of moderate to severe
      obstructive sleep apnea syndrome in major depression. CONCLUSION: Moderate to
      severe obstructive sleep apnea syndrome is a common pathology in major
      depression. The identification of these different risk factors advances a new
      perspective for more effective screening of moderate to severe obstructive sleep
      apnea syndrome in major depression.

PMID- 29202830
TI  - Experiences from the anatomy track in the ontology alignment evaluation
      initiative.
AB  - BACKGROUND: One of the longest running tracks in the Ontology Alignment
      Evaluation Initiative is the Anatomy track which focuses on aligning two anatomy
      ontologies. The Anatomy track was started in 2005. In 2005 and 2006 the task in
      this track was to align the Foundational Model of Anatomy and the OpenGalen
      Anatomy Model. Since 2007 the ontologies used in the track are the Adult Mouse
      Anatomy and a part of the NCI Thesaurus. Since 2015 the data in the Anatomy track
      is also used in the Interactive track of the Ontology Alignment Evaluation
      Initiative. RESULTS: In this paper we focus on the Anatomy track in the years
      2007-2016 and the Anatomy part of the Interactive track in 2015-2016. We describe
      the data set and the changes it went through during the years as well as the
      challenges it poses for ontology alignment systems. Further, we give an overview
      of all systems that participated in the track and the techniques they have used.
      We discuss the performance results of the systems and summarize the general
      trends. CONCLUSIONS: About 50 systems have participated in the Anatomy track.
      Many different techniques were used. The most popular matching techniques are
      string-based strategies and structure-based techniques. Many systems also use
      auxiliary information. The quality of the alignment has increased for the best
      performing systems since the beginning of the track and more and more systems
      check the coherence of the proposed alignment and implement a repair strategy.
      Further, interacting with an oracle is beneficial.

PMID- 29202831
TI  - Heterologous expression, purification and function of the extracellular domain of
      human RANK.
AB  - BACKGROUND: Receptor activator of NF-kappaB ligand (RANKL)/RANK signaling
      essentially functions within the skeletal system, particularly participating in
      osteoclastogenesis and bone resorption. In addition, this signaling pathway has
      also been shown to influence tumor progression as well as the development and
      function of the immune system. Therefore, blocking the interaction between RANKL
      and RANK is a new therapeutic approach to prevent bone-related diseases and
      cancer. RESULTS: The coding sequence encoding the extracellular domain of human
      RANK (RANK-N) was codon optimized for Pichia pastoris and cloned into the pPIC9K
      vector, and the recombinant plasmid was then transformed into P. pastoris. The
      expression of RANK-N protein was confirmed using SDS-PAGE with Coomassie
      Brilliant Blue stain and western blotting. Recombinant RANK-N protein was
      purified by a multistep process including ultrafiltration (UF), Sephadex G-50
      size-exclusion chromatography and Q-Sepharose Fast Flow ion exchange
      chromatography, which resulted in a purity >95%. We found that the RANK-N protein
      can block RANKL-RANK signaling both in vitro and in vivo. Furthermore, using a
      patient-derived xenograft of human colon cancer, we found that the recombinant
      RANK-N protein can inhibit the growth of colorectal cancer. CONCLUSIONS: The
      results show that a simple system to express and purify functional RANK-N protein
      has been developed. This work has thus laid a foundation for further research and
      clinical applications of RANK-N protein in treating bone-related diseases or even
      colorectal cancer.

PMID- 29202832
TI  - Inevitability of the emergence and persistence of genetic parasites caused by
      evolutionary instability of parasite-free states.
AB  - : Genetic parasites, including viruses and mobile genetic elements, are
      ubiquitous among cellular life forms, and moreover, are the most abundant
      biological entities on earth that harbor the bulk of the genetic diversity. Here
      we examine simple thought experiments to demonstrate that both the emergence of
      parasites in simple replicator systems and their persistence in evolving life
      forms are inevitable because the putative parasite-free states are evolutionarily
      unstable. REVIEWERS: This article has been reviewed by Yitzhak Pilpel, Bojan
      Zagrovic, and Eric van Nimwegen.

PMID- 29202833
TI  - Correction to: Diabetes-related information-seeking behaviour: a systematic
      review.
AB  - CORRECTION: During the production process for this article [1] some errors were
      introduced into Table 2. The correct version of Table 2 can be found below; the
      original article [1] has also been updated with the correct version of Table 2.
      BMC apologises to the authors and to readers for this error.

PMID- 29202834
TI  - Development and validation of a preoperative prognostic index independent of TNM
      stage in resected non-small cell lung cancer.
AB  - BACKGROUND: Previously reported prognostic tools for patients with resected non
      small cell lung cancer (NSCLC) include factors found postoperatively, but not
      preoperatively. However, it would be important to predict patient prognosis
      before NSCLC resection. To suggest a novel preoperative prognostic tool, we
      evaluated the relationship of preoperative prognostic factors with the survival
      of patients with resected NSCLC. METHODS: We retrospectively reviewed the data of
      two independent cohorts of patients with completely resected NSCLC. To develop
      the prognostic index in one cohort, the overall survival (OS) was evaluated using
      the Cox proportional hazards model. We assessed the disease-free survival (DFS)
      and OS of three risk groups defined according to the prognostic index. Then, the
      prognostic index was validated in the other cohort. RESULTS: Seven independent
      risk factors for OS were selected: age >= 70 years, ever-smokers, vital capacity
      <80%, neutrophil-to-lymphocyte ratio >= 2.1, cytokeratin 19 fragment >normal
      limit, non-usual interstitial pneumonia (UIP) pattern, and UIP pattern. Three
      risk groups were defined: low-risk (36.9%), intermediate-risk (54.0%), and high
      risk (9.1%). In the derivation cohort, the 5-year DFS rate was 77.8%, 58.8%, and
      22.6% (P < 0.001), and the 5-year OS rate was 95.2%, 70.4%, and 28.9% (P <
      0.001), respectively. Multivariate analyses showed that the prognostic index
      predicted DFS and OS, independent of pathological stage and tumor histology, in
      both derivation and validation cohorts. CONCLUSIONS: We developed and validated a
      simple preoperative prognostic index composed of seven variables, which may help
      clinicians predict prognosis before surgery in patients with NSCLC.

PMID- 29202835
TI  - Coinfection modulates inflammatory responses, clinical outcome and pathogen load
      of H1N1 swine influenza virus and Haemophilus parasuis infections in pigs.
AB  - BACKGROUND: Respiratory co-infections are important factor affecting the
      profitability of pigs production. Swine influenza virus (SIV) may predispose to
      secondary infection. Haemophilus parasuis (Hps) can be a primary pathogen or be
      associated with other pathogens such as SIV. To date, little is known about the
      effect of coinfection with SIV and Hps on the disease severity and inflammatory
      response and the role of Hps in the induction of pneumonia in the absence of
      other respiratory pathogens. In the study we investigated the influence of SIV
      and Hps coinfection on clinical course, inflammatory response, pathogens shedding
      and load at various time points following intranasal inoculation. The correlation
      between local concentration of cytokines and severity of disease as well as serum
      acute phase proteins (APP) concentration has been also studied. RESULTS: All co
      infected pigs had fever, while in single inoculated pigs fever was observed only
      in part of animals. Necropsy revealed lesions in the lungs all SIV-inoculated and
      co-inoculated pigs, while in Hps-single inoculated animals only 1 out of 11 pigs
      revealed gross lung lesions. The SIV shedding was the highest in co-inoculated
      pigs. There were no differences between Hps-single inoculated and co-inoculated
      groups with regard to Hps shedding. The significant increase in Hps titre in the
      lung has been found only in co-inoculated group. All APP increased after co
      infection. In single-inoculated animals various kinetics of APP response has been
      observed. The lung concentrations of cytokines were induced mostly in SIV + Hps
      pigs in the apical and middle lobe. These results correlated well with
      localization of gross lung lesions. CONCLUSIONS: The results revealed that SIV
      increased the severity of lung lesions and facilitated Hps (PIWetHps192/2015)
      replication in the porcine lung. Furthermore, Hps influenced the SIV nasal
      shedding. Enhanced Hps and SIV replication, together with stronger systemic and
      local inflammatory response contributed to a more severe clinical signs and
      stronger, earlier immune response in co-inoculated animals. We confirmed the
      previous evidence that single-Hps infection does not produce significant
      pneumonic lesions but it should be in mind that other strains of Hps may produce
      lesions different from that reported in the present study.

PMID- 29202836
TI  - Global incidence and case fatality rate of pulmonary embolism following major
      surgery: a protocol for a systematic review and meta-analysis of cohort studies.
AB  - BACKGROUND: Pulmonary embolism (PE) is a life-threatening condition common after
      major surgery. Although the high incidence (0.3-30%) and mortality rate (16.9
      31%) of PE in patients undergoing major surgical procedures is apparent from
      findings of contemporary observational studies, there is a lack of a summary and
      meta-analysis data on the epidemiology of postoperative PE in this same regard.
      Hence, we propose to conduct the first systematic review to summarise existing
      data on the global incidence, determinants and case fatality rate of PE following
      major surgery. METHODS: Electronic databases including MEDLINE, EMBASE, SCOPUS,
      WHO global health library (including LILACS), Web of Science and Google scholar
      from inception to April 30, 2017, will be searched for cohort studies reporting
      on the incidence, determinants and case fatality rate of PE occurring after major
      surgery. Data from grey literature will also be assessed. Two investigators will
      independently perform study selection and data extraction. Included studies will
      be evaluated for risk of bias. Appropriate meta-analytic methods will be used to
      pool incidence and case fatality rate estimates from studies with identical
      features, globally and by subgroups of major surgical procedures. Random-effects
      and risk ratio with 95% confidence interval will be used to summarise
      determinants and predictors of mortality of PE in patients undergoing major
      surgery. DISCUSSION: This systematic review and meta-analysis will provide the
      most up-to-date epidemiology of PE in patients undergoing major surgery to inform
      health authorities and identify further research topics based on the remaining
      knowledge gaps. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017065126.

PMID- 29202838
TI  - Development of a Saw Bones Model for training pedicle screw placement in
      scoliosis.
AB  - OBJECTIVE: The purpose of this study was to determine if a Sawbones Scoliosis
      Model could be used as a simulator to train residents in placing pedicle screws-a
      complex procedure with a steep learning curve. Surgical simulation, a common tool
      teaching residents complex procedures in a safe environment, was staged using a
      Sawbones Scoliosis Model. Ten junior and ten senior residents out of 25 total
      possible residents (80%) were instructed how to place pedicle screws using the
      free-hand technique. They were then asked to place them unilaterally from T4 to
      L4 and were assessed on completion time, accuracy placement accuracy, and overall
      competency using an objective rating scale. RESULTS: Senior residents had an
      average time to completion of 38.9 +/- 4.7 min vs. junior's 50.1 +/- 11.7 min,
      and a pedicle screw accuracy of 43.6 +/- 6.4% vs. junior's 44.4 +/- 17.4%.
      Overall competency scores were similar for both groups; however, senior residents
      scored higher in the time and motion subdomain. Senior residents had a faster
      completion time and were more efficient, suggesting greater experience in spine
      surgery. The low rate of screw accuracy in both groups validates that simulation
      is a safe way for trainees to learn complex tasks.

PMID- 29202837
TI  - Predictive power of splenic thickness for post-hepatectomy liver failure in HBV
      associated hepatocellular carcinoma patients.
AB  - BACKGROUND: The purpose of this case series is to investigate the relationship
      between splenic thickness (ST) and postoperative outcomes after hepatic resection
      in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients.
      METHODS: The clinical data of 320 patients with HBV-associated HCC who had
      undergone liver resection were retrospectively analyzed. The value of ST in
      predicting postoperative outcomes was evaluated. RESULTS: A total of 320 patients
      were enrolled in the study. An increase in ST was significantly associated with
      an increase in portal vein diameter (PVD), indocyanine green retention rate 15
      min (ICG R15), and total bilirubin (TBIL); however, it was negatively correlated
      with platelet count (PLT). Post-hepatectomy liver failure (PHLF) occurred in 35
      (10.9%) patients. Multivariate logistic regression analysis showed that ST was an
      independent predictor of morbidity and mortality after hepatectomy. Meanwhile, ST
      was associated with an almost sixfold increased risk for developing perioperative
      complications (OR 5.678; 95% CI 2.873 to 11.224; P < 0.001) and almost 13-fold
      increased risk for mortality after hepatectomy (OR 13.007; 95% CI 1.238 to
      136.627; P = 0.033).The area under the receiver operating characteristic (ROC)
      curve (AUC) of ST for predicting the incidence of PHLF was 0.754 (95% confidence
      interval (CI) 0.667 to 0.841; P < 0.001), with a sensitivity of 57.1% and a
      specificity of 82.5%, which were significantly greater than those of the ICG R15
      level (AUC 0.670; 95% CI 0.560 to 0.779; P < 0.001). The critical value of ST was
      43.5 mm. CONCLUSIONS: ST, which is an easy, inexpensive, and routinely available
      perioperative marker, showed a favorable predictive value for postoperative
      outcomes in HBV-associated HCC patients.

PMID- 29202839
TI  - Choice of surrogate tissue influences neonatal EWAS findings.
AB  - BACKGROUND: Epigenomes are tissue specific and thus the choice of surrogate
      tissue can play a critical role in interpreting neonatal epigenome-wide
      association studies (EWAS) and in their extrapolation to target tissue. To
      develop a better understanding of the link between tissue specificity and
      neonatal EWAS, and the contributions of genotype and prenatal factors, we
      compared genome-wide DNA methylation of cord tissue and cord blood, two of the
      most accessible surrogate tissues at birth. METHODS: In 295 neonates, DNA
      methylation was profiled using Infinium HumanMethylation450 beadchip arrays.
      Sites of inter-individual variability in DNA methylation were mapped and compared
      across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To
      ascertain the similarity to target tissues, DNA methylation profiles of surrogate
      tissues were compared to 25 primary tissues/cell types mapped under the Epigenome
      Roadmap project. Tissue-specific influences of genotype on the variable CpGs were
      also analyzed. Finally, to interrogate the impact of the in utero environment,
      EWAS on 45 prenatal factors were performed and compared across the surrogate
      tissues. RESULTS: Neonatal EWAS results were tissue specific. In comparison to
      cord blood, cord tissue showed higher inter-individual variability in the
      epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal
      tissues were good surrogates for target tissues of mesodermal origin. They also
      showed distinct phenotypic associations, with effect sizes of the overlapping
      CpGs being in the same order of magnitude. CONCLUSIONS: The inter-relationship
      between genetics, prenatal factors and epigenetics is tissue specific, and
      requires careful consideration in designing and interpreting future neonatal
      EWAS. TRIAL REGISTRATION: This birth cohort is a prospective observational study,
      designed to study the developmental origins of health and disease, and was
      retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

PMID- 29202840
TI  - Patient-targeted Googling and social media: a cross-sectional study of senior
      medical students.
AB  - BACKGROUND: Social media and Internet technologies present several emerging and
      ill-explored issues for a modern healthcare workforce. One issue is patient
      targeted Googling (PTG), which involves a healthcare professional using a social
      networking site (SNS) or publicly available search engine to find patient
      information online. The study's aim was to address a deficit in data and
      knowledge regarding PTG, and to investigate medical student use of SNSs due to a
      close association with PTG. METHOD: The authors surveyed final year medical
      students at the Otago Medical School, University of Otago in January 2016. A
      subset completed focus groups that were analysed using thematic analysis to
      identify key themes relating to students' attitudes towards PTG, and reasons why
      they might engage in PTG. RESULTS: Fifty-four students completed the survey
      (response rate = 65.1%), which showed that PTG was uncommon (n = 9, 16.7%).
      Attitudes were varied and context dependent. Most participants saw problems with
      PTG and favoured more explicit guidance on the issue (n = 29, 53.7%). SNS usage
      was high (n = 51, 94.4%); participants were concerned by the content of their SNS
      profiles and who they were connecting with online. Participants showing high SNS
      use were 1.83 times more likely to have conducted PTG than lower use groups.
      CONCLUSIONS: The diverse attitudes uncovered in this study indicated that
      teaching or guidelines could be useful to healthcare professionals considering
      PTG. Though ethically problematic, PTG may be important to patient care and
      safety. The decision to conduct PTG should be made with consideration of ethical
      principles and the intended use of the information.

PMID- 29202841
TI  - The response of canine faecal microbiota to increased dietary protein is
      influenced by body condition.
AB  - BACKGROUND: High protein diets shift the faecal microbiota into a more
      unfavourable composition in obese humans. In lean dogs, higher protein
      consumption is accompanied with increased production of putrefactive fermentation
      products, whereas obese dogs have a different gut microbiota compared to lean
      dogs. Still, the impact of high dietary protein on gut microbiota in obese dogs
      remains unclear. The aim of this study was to investigate faecal microbial
      changes in lean and obese dogs in response to two different levels of dietary
      protein. Six healthy lean and six obese Beagles were fed a high protein diet (HP)
      and a low protein diet (LP) for 28 days each in a crossover design. Denaturing
      gradient gel electrophoresis and quantitative PCR were performed on faecal
      samples for microbial profiling. Plasma acylcarnitine and fermentation
      metabolites were measured. RESULTS: Dogs fed HP had higher concentrations of
      protein fermentation metabolites including faecal ammonia, isovalerate,
      isobutyrate, phenol, indole, serum indoxyl sulphate and plasma 3-OH
      isovalerylcarnitine compared to dogs fed LP, whereas no changes in faecal
      concentrations of acetate and butyrate were observed. The abundances of
      clostridial clusters IV and XIVa, covering the majority of butyrate-producing
      bacteria, and of the butyrate kinase gene, one of the terminal genes of the
      butyrate synthesis pathway were higher in dogs on HP compared to LP. Significant
      interactions between diet and body condition were found for the abundance of
      Firmicutes, Lactobacillus and clostridial cluster I. The similarity coefficient
      of faecal microbiota between the two diets was smaller in obese dogs than in lean
      dogs. CONCLUSIONS: High protein diet increased the abundance and activity of
      butyrate-producing bacteria in Beagles independent of the body condition. In
      addition, increasing dietary protein content had a greater overall impact on
      faecal microbiota in obese compared to lean dogs.

PMID- 29202842
TI  - Preclinical and clinical aspects of TNF-alpha and its receptors TNFR1 and TNFR2
      in breast cancer.
AB  - Breast cancer is the most common malignancy in women and a public health problem
      worldwide. Breast cancer is often accompanied by an inflammatory process
      characterized by the presence of proinflammatory cytokines such as tumor necrosis
      factor (TNF-alpha), which has important implications in the course of the
      disease. Inflammation has been described primarily as a favorable environment for
      tumor development. However, under certain conditions TNF-alpha can promote
      signals for activation, differentiation, survival or cell death, so the study of
      the variants of this cytokine, its receptors, the presence of polymorphisms and
      its implication in different phenotypes of breast cancer is necessary. Although
      the clinical application of TNF-alpha has been limited by its toxicity and side
      effects, preclinical and clinical studies have shown that these effects may
      partially be avoided via tumor-targeted delivery strategies. In this manner, TNF
      alpha alone or combined with chemotherapy and radiotherapy can function as an
      adjuvant in the treatment of breast cancer.

PMID- 29202843
TI  - Socioeconomic inequalities of outpatient and inpatient service utilization in
      China: personal and regional perspectives.
AB  - BACKGROUND: China's health system has shown remarkable progress in health
      provision and health outcomes in recent decades, however inequality in health
      care utilization persists and poses a serious social problem. While government
      pro-poor health policies addressed affordability as the major obstacle to
      equality in health care access, this policy direction deserves further
      examination. Our study examines the issue of health care inequalities in China,
      analyzing both regional and individual socioeconomic factors associated with the
      inequality, and provides evidence to improve governmental health policies.
      METHODS: The China Health and Nutrition Survey (CHNS) 1991-2011 data were used to
      analyze the inequality of health care utilization. The random effects logistic
      regression technique was used to model health care utilization as the dependent
      variable, and income and regional location as the independent variables,
      controlling for individuals' age, gender, marital status, education, health
      insurance, body mass index (BMI), and period variations. The dynamic trend of
      1991-2011 regional disparities was estimated using an interaction term between
      the regional group dummy and the wave dummy. RESULTS: The probability of using
      outpatient service and inpatient services during the previous 4 weeks was 8.6 and
      1.1% respectively. Compared to urban residents, suburban (OR: 0.802, 95% CI:
      0.720-0.893), town (OR: 0.722, 95% CI: 0.648-0.804), rich (OR: 0.728, 95% CI:
      0.656-0.807) and poor village (OR: 0.778, 95% CI: 0.698-0.868) residents were
      less likely to use outpatient service; and rich (OR: 0.609, 95% CI: 0.472-0.785)
      and poor village (OR: 0.752, 95% CI: 0. 576-0.983) residents were less likely to
      use inpatient health care. But the differences between income groups were not
      significant, except the differences between top and bottom income group in
      outpatient service use. CONCLUSION: Regional location was a more important factor
      than individual characteristics in determining access to health care. Besides
      demand-side subsidies, Chinese policy makers should pay enhanced attention to
      health care resource allocation to address inequity in health care access.

PMID- 29202844
TI  - Associations between fruit and vegetable, and antioxidant nutrient intake and age
      related macular degeneration by smoking status in elderly Korean men.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of
      irreversible blindness. The objective of this study was to determine whether
      there is any relationship between dietary intake of fruits and vegetables (F&V)
      and antioxidant nutrients including carotenoids and AMD according to smoking
      status in elderly men. METHODS: We performed a cross-sectional analysis using
      nationally representative samples of elderly aged >= 65 years (n = 1414) from the
      Korea National Health and Nutrition Examination Survey (KNHANES, 2010-2012).
      RESULTS: The current smokers consumed less food in total, and, in particular,
      less cereals/potatoes/sugar products, fruits and vegetables than the nonsmokers
      and former smokers (p < 0.05). Intake of energy, thiamin, vitamin C, vitamin A,
      and beta-carotene were significantly lower in the current smokers than in the
      nonsmokers and the former smokers. For current smokers, the ORs of the highest
      tertile compared with the lowest tertile were 0.36 (95% CI: 0.14-0.96, p for
      trend = 0.0576) for F&V, 0.32 (95% CI: 0.12-0.85, p for trend = 0.0561) for
      vitamin C, 0.23 (95% CI: 0.08-0.67, p for trend = 0.0038) for alpha-carotene,
      0.13 (95% CI: 0.04-0.46, p for trend = 0.0003) for beta-carotene after adjusting
      for confounding factors. In contrast, there was no association between
      antioxidant nutrient intake and AMD among the nonsmokers and former smokers.
      CONCLUSIONS: These results suggest that increased consumption of fruits and
      vegetables containing antioxidant components such as vitamin C, alpha-carotene,
      and beta-carotene may have a protective effect on AMD. These effects may be more
      evident among current smokers.

PMID- 29202845
TI  - Robotic assisted gait as a tool for rehabilitation of individuals with spinal
      cord injury: a systematic review.
AB  - BACKGROUND: Spinal cord injury (SCI) is characterized by a total or partial
      deficit of sensory and motor pathways. Impairments of this injury compromise
      muscle recruitment and motor planning, thus reducing functional capacity. SCI
      patients commonly present psychological, intestinal, urinary, osteomioarticular,
      tegumentary, cardiorespiratory and neural alterations that aggravate in chronic
      phase. One of the neurorehabilitation goals is the restoration of these abilities
      by favoring improvement in the quality of life and functional independence.
      Current literature highlights several benefits of robotic gait therapies in SCI
      individuals. OBJECTIVES: The purpose of this study was to compare the robotic
      gait devices, and systematize the scientific evidences of these devices as a tool
      for rehabilitation of SCI individuals. METHODS: A systematic review was carried
      out in which relevant articles were identified by searching the following
      databases: Cochrane Library, PubMed, PEDro and Capes Periodic. Two authors
      selected the articles which used a robotic device for rehabilitation of spinal
      cord injury. RESULTS: Databases search found 2941 articles, 39 articles were
      included due to meet the inclusion criteria. The robotic devices presented
      distinct features, with increasing application in the last years. Studies have
      shown promising results regarding the reduction of pain perception and spasticity
      level; alteration of the proprioceptive capacity, sensitivity to temperature,
      vibration, pressure, reflex behavior, electrical activity at muscular and
      cortical level, classification of the injury level; increase in walking speed,
      step length and distance traveled; improvements in sitting posture, intestinal,
      cardiorespiratory, metabolic, tegmental and psychological functions. CONCLUSIONS:
      This systematic review shows a significant progress encompassing robotic devices
      as an innovative and effective therapy for the rehabilitation of individuals with
      SCI.

PMID- 29202846
TI  - Haplotypes inside the beta-globin gene: use as new biomarkers for beta
      thalassemia prenatal diagnosis in north of Iran.
AB  - BACKGROUND: Beta-thalassemia is common in the Mediterranean area as well as the
      Middle East and India. Official report in Iran revealed the average prevalence
      rate of carriers about 4%. More than 20 restriction fragment length polymorphisms
      (RFLPs) are known in the beta-globin gene cluster and used in the prenatal
      diagnosis (PND) services. Some of these locations may have low allele frequency
      and are not informative in the prenatal diagnosis. The current study aims to find
      new haplotypes and polymorphisms with high allele frequency in the local
      population. METHODS: Two thousand three hundred fifty samples (1,321 male and
      1,029 female) from the northern Iran, whom suspected to be the carriers either
      for alpha or beta thalassemia and referred to the local diagnostic laboratory as
      a routine services were investigated during five years, (2010-2015). The beta
      globin gene was sequenced for all samples. RESULTS: Heterozygosity for five SNPs
      in the beta-globin gene was calculated separately. 383 individuals (16.29%)
      showed no sign of nucleotide change in the beta-globin gene sequence. In total,
      codon2 (C/T) 31.72%, IVSII-16 (C/G) 31.72%, IVSII-74 (G/T) 54.71%, IVSII-81 (C/T)
      19.47%, and IVSII-666 (T/C) 31.72% were seen respectively. Although all five
      polymorphisms showed reasonably high heterozygosity, IVSII-74 (G/T) [GG wild type
      (36.5%), G/T (54.71%) and TT (8.8%)] revealed the highest heterozygosity rate.
      Four combinations of these five SNPs were defined as new haplotypes named M1 to
      M4. ARMS-PCR also were designed and applied to detect IVSII-74 (G/T) nucleotide
      position. CONCLUSIONS: This study represents an intragenic polymorphism, IVSII
      74, a reliable position with high heterozygosity rates in Iranian population for
      PND analysis. TRIAL REGISTRATION: Retrospectively registered.

PMID- 29202847
TI  - Effects of adenosine and regadenoson on hemodynamics measured using
      cardiovascular magnetic resonance imaging.
AB  - BACKGROUND: Adenosine or regadenoson vasodilator stress cardiovascular magnetic
      resonance (CMR) is an effective non-invasive strategy for evaluating symptomatic
      coronary artery disease. Vasodilator injection typically precedes ventricular
      functional sequences to efficiently reduce overall scanning times, though the
      effects of vasodilators on CMR-derived ventricular volumes and function are
      unknown. METHODS: We prospectively enrolled 25 healthy subjects to undergo
      consecutive adenosine and regadenoson administration. Short axis CINE datasets
      were obtained on a 1.5 T scanner following adenosine (140mcg/kg/min IV for 6 min)
      and regadenoson (0.4 mg IV over 10 s) at baseline, immediately following
      administration, at 5 min intervals up to 15 min. Hemodynamic response, bi
      ventricular volumes and ejection fractions were determined at each time point.
      RESULTS: Peak heart rate was observed early following administration of both
      adenosine and regadenoson. Heart rate returned to baseline by 10 min post
      adenosine while remaining elevated at 15 min post-regadenoson (p = 0.0015). Left
      ventricular (LV) ejection fraction (LVEF) increased immediately following both
      vasodilators (p < 0.0001 for both) and returned to baseline following adenosine
      by 10 min (p = 0.8397). Conversely, LVEF following regadenoson remained increased
      at 10 min (p = 0.003) and 15 min (p = 0.0015) with a mean LVEF increase at 15 min
      of 4.2 +/- 1.3%. Regadenoson resulted in a similar magnitude reduction in both LV
      end-diastolic volume index (LVEDVi) and LV end-systolic volume index (LVESVi) at
      15 min whereas LVESVi resolved at 15 min following adenosine and LVEDVi remained
      below baseline values (p = 0.52). CONCLUSIONS: Regadenoson and adenosine have
      significant and prolonged impact on ventricular volumes and LVEF. In patients
      undergoing vasodilator stress CMR where ventricular volumes and LVEF are critical
      components to patient care, ventricular functional sequences should be performed
      prior to vasodilator use or consider the use of aminophylline in the setting of
      regadenoson. Additionally, heart rate resolution itself is not an effective
      surrogate for return of ventricular volumes and LVEF to baseline.

PMID- 29202848
TI  - Downregulation of miR-141-3p promotes bone metastasis via activating NF-kappaB
      signaling in prostate cancer.
AB  - BACKGROUND: Clinically, prostate cancer (PCa) exhibits a high avidity to
      metastasize to bone. miR-141-3p is an extensively studied miRNA in cancers and
      downregulation of miR-141-3p has been widely reported to be involved in the
      progression and metastasis of several human cancer types. However, the clinical
      significance and biological roles of miR-141-3p in bone metastasis of PCa are
      still unclear. METHODS: miR-141-3p expression was examined in 89 non-bone
      metastatic and 52 bone metastatic PCa tissues by real-time PCR. Statistical
      analysis was performed to investigate the clinical correlation between miR-141-3p
      expression levels and clinicopathological characteristics in PCa patients. The
      biological roles of miR-141-3p in bone metastasis of PCa were evaluated both in
      vitro and a mouse intracardial model in vivo. Bioinformatics analysis, Western
      blot, luciferase reporter and miRNA immunoprecipitation assays were performed to
      explore and examine the relationship between miR-141-3p and its potential
      targets. Clinical correlation of miR-141-3p with its targets was examined in
      clinical PCa tissues. RESULTS: miR-141-3p expression is reduced in bone
      metastatic PCa tissues compared with non-bone metastatic PCa tissues. Low
      expression of miR-141-3p positively correlates with serum PSA levels, Gleason
      grade and bone metastasis status in PCa patients. Furthermore, upregulating miR
      141-3p suppresses the EMT, invasion and migration of PCa cells in vitro.
      Conversely, silencing miR-141-3p yields an opposite effect. Importantly,
      upregulating miR-141-3p dramatically reduces bone metastasis of PC-3 cells in
      vivo. Our results further show that miR-141-3p inhibits the activation of NF
      kappaB signaling via directly targeting tumor necrosis factor receptor-associated
      factor 5(TRAF5) and 6 (TRAF6), which further suppresses invasion, migration and
      bone metastasis of PCa cells. The clinical negative correlation of miR-141-3p
      expression with TRAF5, TRAF6 and NF-kappaB signaling activity is demonstrated in
      PCa tissues. CONCLUSION: Our findings unravel a novel mechanism underlying the
      bone metastasis of PCa, suggesting that miR-141-3p mimics might represent a
      potential therapeutic avenue for the treatment of PCa bone metastasis.

PMID- 29202849
TI  - Designing healthy communities: creating evidence on metrics for built environment
      features associated with walkable neighbourhood activity centres.
AB  - BACKGROUND: Evidence-based metrics are needed to inform urban policy to create
      healthy walkable communities. Most active living research has developed metrics
      of the environment around residential addresses, ignoring other important walking
      locations. Therefore, this study examined: metrics for built environment features
      surrounding local shopping centres, (known in Melbourne, Australia as
      neighbourhood activity centres (NACs) which are typically anchored by a
      supermarket); the association between NACs and transport walking; and, policy
      compliance for supermarket provision. METHODS: In this observational study,
      cluster analysis was used to categorize 534 NACs in Melbourne, Australia by their
      built environment features. The NACS were linked to eligible Victorian Integrated
      Survey of Travel Activity 2009-2010 (VISTA) survey participants (n=19,984).
      Adjusted multilevel logistic regressions estimated associations between each
      cluster typology and two outcomes of daily walking: any transport walking; and,
      any 'neighbourhood' transport walking. Distance between residential dwellings and
      closest NAC was assessed to evaluate compliance with local planning policy on
      supermarket locations. RESULTS: Metrics for 19 built environment features were
      estimated and three NAC clusters associated with walkability were identified.
      NACs with significantly higher street connectivity (mean:161, SD:20), destination
      diversity (mean:16, SD:0.4); and net residential density (mean:77, SD:65) were
      interpreted as being 'highly walkable' when compared with 'low walkable' NACs,
      which had lower street connectivity (mean:57, SD:15); destination diversity
      (mean:11, SD:3); and net residential density (mean:10, SD:3). The odds of any
      daily transport walking was 5.85 times higher (95% CI: 4.22, 8.11), and for any
      'neighborhood' transport walking 8.66 (95% CI: 5.89, 12.72) times higher, for
      residents whose closest NAC was highly walkable compared with those living near
      low walkable NACs. Only highly walkable NACs met the policy requirement that
      residents live within 1km of a local supermarket. CONCLUSIONS: Built environment
      features surrounding NACs must reach certain levels to encourage walking and
      deliver walkable communities. Research and metrics about the type and quantity of
      built environment features around both walking trip origins and destinations is
      needed to inform urban planning policies and urban design guidelines.

PMID- 29202851
TI  - Female genital tuberculosis and infertility: serial cases report in Bandung,
      Indonesia and literature review.
AB  - BACKGROUND: Female genital tuberculosis (FGTB) is a Mycobacterium infection in
      the reproductive organs which often leads to infertility. FGTB is either
      asymptomatic or causes uncharacteristic clinical presentations, making an early
      diagnosis is challenging. Our aims were to evaluate the clinical presentations,
      the process to confirm the diagnosis and followed-up the patients who had
      undergone laparoscopy at our center. FGTB has been reported from many countries,
      but has never been reported from Indonesia. Here we present case studies to
      document the presence of FGTB in Indonesia. CASES PRESENTATION: There were three
      patients admitted to our center; two patients were admitted with irregular
      menstrual cycle as their chief complaint, while one patient came due to
      infertility. The results from laparoscopy were suggestive of FGTB; including the
      presence of caseating granulomas surrounded by epithelioid cells, lymphocytes,
      plasma cells, and Langhans giant cells. Additionally, PCR testing confirmed
      presence of MTB. Subsequent to diagnosis, continuous TB medications was
      administered with excellent clinical outcome in two patients (pregnant in 18
      months after under gone laparoscopy). The infertile patient remain in one of the
      treated patient above. CONCLUSION: In infertile patients who live in countries
      where Tuberculosis is an endemic disease, such as Indonesia, a comprehensive
      history taking, along with ultrasonography results can be used to diagnose FGTB.
      Confirmation of this diagnosis can be achieved through polymerase chain reactions
      result. Timely diagnosis and treatment are imperative to prevent any permanent
      injury to patient's reproductive organs.

PMID- 29202850
TI  - Objectively-assessed physical activity and weight change in young adults: a
      randomized controlled trial.
AB  - BACKGROUND: Reductions in physical activity (PA) are common throughout young
      adulthood and low PA is associated with weight gain. The SNAP Trial previously
      reported that two self-regulation approaches to weight gain prevention reduced
      weight gain over a 2-year period in 18-35 year olds. Presented here are secondary
      analyses examining changes in PA and the relationship between PA and weight
      change over 2 years. METHODS: 599 young adults (age: 27.4 +/- 4.4 yrs.; BMI: 25.4
      +/- 2.6 kg/m2) were randomly assigned to 1 of 3 treatment arms: Small Changes
      (reduce calorie intake by 100 kcals/day & add 2000 steps/day), Large Changes
      (lose 2.3-4.5 kg initially & increase PA to >=250 min/wk), or Self-guided
      (control condition). Small and Large Changes received 10, face-to-face group
      sessions (months 1-4), and two 4-week refresher courses each subsequent year.
      Body weight and PA were objectively-measured at baseline, 4 months, 1 and 2
      years. Daily steps and bout-related moderate-to-vigorous intensity PA (MVPA: >=3
      METs, >=10-min bouts) was calculated. RESULTS: Changes in bout-related MVPA and
      daily steps did not differ among treatment groups over the 2-year period (p's >
      0.16). Collapsed across groups, participants gaining >1 lb. (n = 187; 39.6%) had
      smaller changes in bout-related MVPA at 4 months, 1 and 2 years relative to those
      maintaining or losing weight (<=1 lb. weight gain; n = 282, 60.4%, p's < 0.05).
      Averaged across time points, this difference equated to 47.8 min/week. Those
      gaining and not gaining >1 lb. did not differ on daily steps (p's > 0.10). Among
      participants engaging in >=250 min/wk. of MVPA at 2 years (n = 181), 30% gained
      >1 lb. from baseline to 2 years, which was not different from those engaging in
      150-250 min/wk. (n = 87; 36%; p = 0.40), but this percentage was significantly
      lower when compared to those engaging in <150 min/wk. (n = 176; 49%; p < 0.001).
      CONCLUSIONS: On average, PA differences were not observed between young adults
      assigned to small or large changes self-regulation interventions to prevent
      weight gain. Regardless of group assignment, higher levels of MVPA were
      associated with better weight gain prevention over 2 years. Our data suggest that
      achieving >150 min/week of MVPA is needed for weight gain prevention and that
      increasing MVPA, rather than steps, should be targeted. TRIAL REGISTRATION:
      www.clinicaltrials.gov (NCT01183689). Registered Aug 13, 2010.

PMID- 29202852
TI  - Nutrition education for cardiovascular disease prevention in individuals with
      spinal cord injuries: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Individuals with chronic spinal cord injuries (SCIs) have an
      increased prevalence of cardiovascular disease (CVD) and associated risk factors
      compared with age-matched control subjects. Exercise has been shown to improve
      selected CVD risk factors in individuals with SCI, but using nutrition education
      as an intervention has not been evaluated in this population. This paper
      describes our research plan for evaluating the effect of nutrition education on
      individuals with SCI. In the present study, called Eat Smart, Live Better, we are
      using a randomized controlled design to test an intervention adapted from an
      existing evidence-based program that showed a positive effect on nutrition
      knowledge and behavior of older adults from the general population. There will be
      an inpatient group (n = 100) and a community group (n = 100). The aims of our
      study are to compare the intervention and control groups for (1) changes in
      nutritional behavior, nutritional knowledge, and dietary quality by participants
      in the program; (2) levels of adiposity and metabolic CVD risk factors at 12
      month follow-up; and (3) differential effects among individuals with SCI in the
      acute rehabilitation setting and those living in the community. METHODS/DESIGN:
      This is a randomized controlled trial of nutrition education. The treatment
      groups receive six nutrition education sessions. The control groups receive the
      one "standard of care" nutrition lecture that is required by the Commission on
      Accreditation of Rehabilitation Facilities. Treatment groups include both an
      inpatient group, comprising patients who have been admitted to an acute
      rehabilitation facility because of their recent SCI, and an outpatient group,
      consisting of community-dwelling adults who are at least 1 year after their SCI.
      A total of 200 participants will be randomized 1:1 to the intervention or control
      group, stratified by location (acute rehabilitation facility or community
      dwelling). DISCUSSION: To our knowledge, this will be the first reported study of
      nutrition education in individuals with SCI. The low cost and feasibility of the
      intervention, if shown to improve nutritional behavior, suggests that it could be
      implemented in rehabilitation facilities across the country. This has the
      potential of lowering the burden of CVD and CVD risk factors in this high-risk
      population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02368405 . Registered on
      February 10, 2015.

PMID- 29202853
TI  - Increased PKMzeta activity impedes lateral movement of GluA2-containing AMPA
      receptors.
AB  - Protein kinase M zeta (PKMzeta), a constitutively active, atypical protein kinase
      C isoform, maintains a high level of expression in the brain after the induction
      of learning and long-term potentiation (LTP). Further, its overexpression
      enhances long-term memory and LTP. Thus, multiple lines of evidence suggest a
      significant role for persistently elevated PKMzeta levels in long-term memory.
      The molecular mechanisms of how synaptic properties are regulated by the increase
      in PKMzeta, however, are still largely unknown. The alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) mediates most of the
      fast glutamatergic synaptic transmission in the brain and is known to be critical
      for the expression of synaptic plasticity and memory. Importance of AMPAR
      trafficking has been implicated in PKMzeta-mediated cellular processes, but the
      detailed mechanisms, particularly in terms of regulation of AMPAR lateral
      movement, are not well understood. In the current study, using a single-molecule
      live imaging technique, we report that the overexpression of PKMzeta in
      hippocampal neurons immobilized GluA2-containing AMPARs, highlighting a potential
      novel mechanism by which PKMzeta may regulate memory and synaptic plasticity.

PMID- 29202854
TI  - Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain
      during acute virus infection.
AB  - BACKGROUND: Viral encephalitis is a dangerous compromise between the need to
      robustly clear pathogen from the brain and the need to protect neurons from
      bystander injury. Theiler's murine encephalomyelitis virus (TMEV) infection of
      C57Bl/6 mice is a model of viral encephalitis in which the compromise results in
      hippocampal damage and permanent neurological sequelae. We previously identified
      brain-infiltrating inflammatory monocytes as the primary driver of this
      hippocampal pathology, but the mechanisms involved in recruiting these cells to
      the brain were unclear. METHODS: Chemokine expression levels in the hippocampus
      were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte
      infiltration during acute TMEV infection was measured by flow cytometry. CCL2
      levels were manipulated by immunodepletion and by specific removal from neurons
      in mice generated by crossing a line expressing the Cre recombinase behind the
      synapsin promoter to animals with floxed CCL2. RESULTS: Inoculation of the brain
      with TMEV induced hippocampal production of the proinflammatory chemokine CCL2
      that peaked at 6 h postinfection, whereas inoculation with UV-inactivated TMEV
      did not elicit this response. Immunofluorescence revealed that hippocampal
      neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2
      and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of
      inflammatory monocytes into the brain during acute infection. Specific genetic
      deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and
      inhibited inflammatory monocyte infiltration into the brain. CONCLUSIONS: We
      conclude that intracranial inoculation with infectious TMEV rapidly induces the
      expression of CCL2 in neurons, and this cellular source is necessary for CCR2
      dependent infiltration of inflammatory monocytes into the brain during the most
      acute stage of encephalitis. These findings highlight a unique role for neuronal
      production of chemokines in the initiation of leukocytic infiltration into the
      infected central nervous system.

PMID- 29202855
TI  - Soluble CD73 as biomarker in patients with metastatic melanoma patients treated
      with nivolumab.
AB  - BACKGROUND: Nivolumab is an anti-PD1 checkpoint inhibitor active in patients with
      advanced melanoma and as adjuvant therapy in high-risk metastatic melanoma
      patients. METHODS: In this single-center retrospective analysis, we investigated
      the CD73 enzyme activity in patients with metastatic melanoma stage IV and its
      correlation with the response to nivolumab. The soluble CD73 (sCD73) enzyme
      activity was measured in the serum of 37 melanoma patients before receiving
      nivolumab and the Harrel's C index was used to find the best cut-off for this
      biomarker. The multivariate Cox proportional hazard model was used to evaluate
      the prognostic value of CD73 enzyme activity for survival and progression-free
      survival. RESULTS: Our results show that high levels of sCD73 enzyme activity
      were significantly associated with poor overall survival and progression-free
      survival in patients with metastatic melanoma. The median progression-free
      survival was 2.6 months [95% confidence interval (CI) 1.9-3.3] in patients with
      high sCD73 enzyme activity (> 27.8 pmol/min/mg protein), and 14.2 months (95% CI
      4.6-23.8) in patients with lower CD73 enzyme activity, when patients were follow
      up for a median of 24 months range. The median overall survival was not reached
      in patients with low sCD73 activity (< 27.8 pmol/min/mg protein) compared with
      6.1 months (95% CI 0-14.8) in patients with higher sCD73 activity. In
      multivariate analyses, the sCD73 enzyme activity emerged as the strongest
      prognostic factor for overall survival and progression-free survival. Elevated
      basal levels of sCD73 enzyme activity, before starting nivolumab treatment, were
      associated with lower response rates to therapy. CONCLUSIONS: We observed a
      significant association between the activity of sCD73 in the blood and clinical
      outcomes in patients with metastatic melanoma stage IV, receiving nivolumab.
      Although our results need to be confirmed and validated, we suggest that sCD73
      might be used as serologic prognostic biomarker. Potentially evaluating sCD73
      enzyme activity in the peripheral blood before treatment could help to estimate
      the response to nivolumab.

PMID- 29202857
TI  - Medication adherence and its associated factors among diabetic patients at
      Zewditu Memorial Hospital, Addis Ababa, Ethiopia.
AB  - OBJECTIVE: Diabetes is a global problem with devastating human, social and
      economic impact. Anti-diabetic medications play a major role in the glycemic
      control of patients with diabetes. However, inadequate adherence compromises
      safety and treatment effectiveness, leading to increased mortality and morbidity.
      The aim of this study was to assess adherence to anti-diabetic medications and
      associated factors among patient with diabetes mellitus receiving care at Zewditu
      Memorial Hospital. RESULTS: Among the total of 146 diabetic patients (mean age
      46.5 +/- 14.7), the level of adherence to anti diabetic medication was 54.8% (80)
      whilst 45.2% (66) of the participants were non adherent. Multiple logistic
      regression showed that knowledge of medication (AOR = 4.905, 95% CI 1.64-14.62,
      medication availability (AOR = 0.175, 95% CI 0.031-0.987) and education level
      (AOR = 13.65, 95% CI 1.45-128.456) were reasons for non-adherence.

PMID- 29202856
TI  - Sulfosuccinimidyl oleate sodium is neuroprotective and alleviates stroke-induced
      neuroinflammation.
AB  - BACKGROUND: Ischemic stroke is one of the main causes of death and disability
      worldwide. It is caused by the cessation of cerebral blood flow resulting in the
      insufficient delivery of glucose and oxygen to the neural tissue. The
      inflammatory response initiated by ischemic stroke in order to restore tissue
      homeostasis in the acute phase of stroke contributes to delayed brain damage.
      METHODS: By using in vitro models of neuroinflammation and in vivo model of
      permanent middle cerebral artery occlusion, we demonstrate the neuroprotective
      and anti-inflammatory effects of sulfosuccinimidyl oleate sodium (SSO). RESULTS:
      SSO significantly reduced the lipopolysaccharide/interferon-gamma-induced
      production of nitric oxide, interleukin-6 and tumor necrosis factor-alpha, and
      the protein levels of inflammatory enzymes including nitric oxide synthase 2,
      cyclooxygenase-2 (COX-2), and p38 mitogen-activated protein kinase (MAPK) in
      microglia, without causing cell toxicity. Although SSO failed to directly
      alleviate glutamate-induced excitotoxicity in murine cortical neurons, it
      prevented inflammation-induced neuronal death in microglia-neuron co-cultures.
      Importantly, oral administration of SSO in Balb/c mice subjected to permanent
      occlusion of the middle cerebral artery reduced microglial activation in the peri
      ischemic area and attenuated brain damage. This in vivo neuroprotective effect of
      SSO was associated with a reduction in the COX-2 and heme oxygenase-1
      immunoreactivities. CONCLUSIONS: Our results suggest that SSO is an anti
      inflammatory and a possible therapeutic candidate in diseases such as stroke
      where inflammation is a central hallmark.

PMID- 29202858
TI  - Molecular and biochemical characterization of calmodulin from Echinococcus
      granulosus.
AB  - BACKGROUND: Echinococcus granulosus is a harmful cestode parasite that causes
      cystic echinococcosis in humans as well as various livestock species and wild
      animals. Calmodulin (CaM), a Ca2+ sensor protein, is widely expressed in
      eukaryotes and mediates a variety of cellular signaling activities. METHODS: In
      the present study, the cDNA encoding CaM in Echinococcus granulosus (rEgCaM) was
      successfully cloned and the molecular and biochemical characterizations carried
      out. The antigenicity and immunoreactivity of rEgCaM was detected and the
      preliminary enzyme-linked immunosorbent assay (ELISA)-based serodiagnostic
      potential of EgCaM was assessed. The locations of this protein in the adult worm
      and larval stage, and the mRNA expression in different states of E. granulosus
      protoscoleces (PSCs) were defined clearly. Moreover, the Ca2+-binding properties
      of EgCaM were measured. RESULTS: rEgCaM is a highly conserved calcium-binding
      protein, consisting of 149 amino acids. Immunoblotting analysis revealed that
      rEgCaM could be identified using E. granulosus infected sheep serum. The use of
      rEgCaM as an antigen was evaluated by indirect ELISA which exhibited a high
      sensitivity (90.3%), but low specificity (47.1%). rEgCaM was ubiquitously
      expressed in protoscoleces and adults of E. granulosus, as well as in the
      germinal layer of the cyst wall. The mRNA expression level of rEgCaM was
      increased from the start of H2O2 exposure and then gradually decreased because of
      the increased apoptosis of PSCs. In electrophoretic mobility tests and 1
      anilinonaphthalene-8-sulfonic acid assays, rEgCaM showed a typical characteristic
      of a calcium-binding protein. CONCLUSIONS: To our knowledge, this is the first
      report on CaM from E. granulosus and rEgCaM is likely to be involved in some
      important biological function of E. granulosus as a calcium-binding protein.

PMID- 29202859
TI  - Complications of lumbar disc herniations following trans-sacral epiduroscopic
      lumbar decompression: a single-center, retrospective study.
AB  - BACKGROUND: Trans-sacral epiduroscopic lumbar decompression (SELD) is an emerging
      procedure for the treatment of lumbar disc herniation (LDH), with favorable
      outcomes having been reported. However, the complications associated with SELD
      have not been comprehensively evaluated to date. Therefore, the aim of our study
      was to describe the incidence rate, types, and characteristics of complications
      following SELD and management outcomes. METHODS: Retrospective analysis of the
      surgical and clinical outcomes for 127 patients (average age, 42.2 +/- 15.2
      years) who underwent SELD for LDH at L2-3, L3-4, L4-5, and/or L5-S1, performed by
      a single experienced spine surgeon at a single center, between January 2015 and
      April 2017, was conducted. RESULTS: All procedures were successful, with a mean
      follow-up of 12.3 +/- 2.3 months. Complications were identified in 8 patients
      (6.3%), including 3 cases of incomplete decompression (2.4%), 2 cases of
      recurrent disc herniation (1.6%), and one case each of hematoma, dural tearing,
      and subchondral osteonecrosis (0.8%). Among these cases with complications, only
      2 cases with incomplete decompression and one case with recurrent LDH did not
      improve with conservative treatment and required re-operation using an open
      approach. The rate of complications decreased from 12.6% when considering only
      the first 50 cases to 2.6% for cases 51-127. CONCLUSIONS: Incomplete
      decompression, recurrent herniation, epidural hematoma, dural tear, and
      subchondral osteonecrosis were identified as complications of SELD, although the
      overall rate of complications was low. Practice with the procedure and careful
      patient selection can lower the risk of complications.

PMID- 29202860
TI  - A giant popliteal lipoblastoma in a 23-month-old girl: a case report.
AB  - BACKGROUND: Lipoblastomas are rare benign tumors that arise from embryonic white
      fat and almost always occur in babies and children. Here, we report a case of a
      giant popliteal lipoblastoma in a 23-month-old Japanese girl that was
      successfully treated via complete resection. CASE PRESENTATION: Our patient was a
      23-month-old Japanese girl. At 6 months of age, she presented at a nearby
      hospital with a mass on the popliteal side of her lower right leg. She had no
      symptoms and was diagnosed as having a benign adipose tumor via magnetic
      resonance imaging. The mass gradually increased in size, and she was referred to
      our hospital at 1 year and 11 months of age. A physical examination and radiology
      revealed a localized mass 13 * 10 * 7 cm in size in the aforementioned area that
      restricted knee movement and caused proximal tibia deformity. Magnetic resonance
      imaging showed a giant circumscribed subcutaneous mass with multiple partitions
      that was hyperintense on T1-weighted and T2-weighted images but not fat-saturated
      on T2-weighted images. Based on these findings, she was diagnosed as having a
      lipoblastoma. Because the mass surrounded her popliteal artery and vein and part
      of the popliteal nerve, surgical resection was considered risky, and we opted to
      simply observe her. However, owing to rapid growth of the mass and the worsening
      of symptoms, she underwent complete resection at 2 years and 6 months of age. A
      histological examination confirmed the diagnosis of a lipoblastoma. She was
      discharged from our hospital 3 days after surgery with no symptoms. She could
      walk without pain at the 6-month follow-up, and no local recurrence was observed.
      CONCLUSIONS: We successfully treated a giant popliteal lipoblastoma without
      complications by performing a total resection. Our report provides evidence that
      lipoblastomas should be considered for surgical resection when they progress or
      symptoms appear.

PMID- 29202861
TI  - The McMaster Toronto Arthritis patient preference questionnaire (MACTAR): a
      methodological study of reliability and minimal detectable change after a 6 week
      period of acupuncture treatment in patients with rheumatoid arthritis.
AB  - OBJECTIVES: The McMaster Toronto Arthritis patient preference questionnaire
      (MACTAR) is a semi-structured interview consisting of a baseline and a follow-up
      interview. The MACTAR baseline is reliable and valid, however the reliability of
      the MACTAR follow-up is scarcely described. The aim of this study was to describe
      aspects of reliability and ability to detect changes of the Swedish MACTAR follow
      up following acupuncture treatment in individuals with rheumatoid arthritis.
      RESULTS: The study was of Single Subject Experimental Design, with a 2-week non
      interventional A-phase and a 6-week intervention B-phase. Eight individuals with
      RA, age 30-68 years, were included. MACTAR baseline was performed once followed
      by five assessments with MACTAR follow-up during the A-phase and another ten
      assessments during the B-phase. Reliability statistics were calculated for
      measurements 1-3 during the A-phase and the ability to detect effects of
      acupuncture treatment was tested by celeration lines in the B-phase. The MACTAR
      follow-up was highly reliable (ICC = 0.7-0.9, SEM = 2.3-4.3, and SDD = 6.2-11.7).
      Visual and statistical analyses indicated that the MACTAR follow-up could detect
      effects on individual- and group levels after acupuncture treatment, indicating
      that the MACTAR follow-up seems to be reliable and is able to detect effects of
      acupuncture treatment in RA.

PMID- 29202862
TI  - Coping with Unusual ExperienceS for 12-18 year olds (CUES+): a transdiagnostic
      randomised controlled trial of the effectiveness of cognitive therapy in reducing
      distress associated with unusual experiences in adolescent mental health
      services: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Childhood 'unusual experiences' (such as hearing voices that others
      cannot, or suspicions of being followed) are common, but can become more
      distressing during adolescence, especially for young people in contact with Child
      and Adolescent Mental Health Services (CAMHS). Unusual experiences that are
      distressing or have adverse life impact (UEDs) are associated with a range of
      current and future emotional, behavioural and mental health difficulties.
      Recommendations for psychological intervention are based on evidence from adult
      studies, with some support from small, pilot, child-specific evaluations.
      Research is needed to ensure that the recommendations suit children as well as
      adults. The CUES+ study (Coping with Unusual ExperienceS for 12-18 year olds)
      aims to find out whether cognitive behaviour therapy for UEDs (CBT-UED) is a
      helpful and cost-effective addition to usual community care for 12-18 year olds
      presenting to United Kingdom National Health Service Child and Adolescent Mental
      Health Services in four London boroughs. METHODS: The CUES+ study is a randomised
      controlled trial comparing CBT-UED plus routine care to routine care alone. CBT
      UED comprises up to 16 sessions, including up to 12 individual and up to four
      family support meetings, each lasting around 45-60 min, delivered weekly. The
      primary outcome is emotional distress. Secondary outcomes are change in UEDs,
      risk events (self-harm, attendance at emergency services, other adverse events)
      and health economic outcomes. Participants will be randomised in a 1:1 ratio
      after baseline assessment. Randomisation will be stratified by borough and by
      severity of mental health presentation: 'severe' (an identified psychotic or
      bipolar disorder) or any 'other' condition. Outcomes will be assessed by a
      trained assessor blind to treatment condition at 0, 16 and 24 weeks. Recruitment
      began in February, 2015 and is ongoing until the end of March, 2017. DISCUSSION:
      The CUES+ study will contribute to the currently limited child-specific evidence
      base for psychological interventions for UEDs occurring in the context of
      psychosis or any other mental health presentation. TRIAL REGISTRATION:
      International Standard Randomised Controlled Trials, ID: ISRCTN21802136 .
      Prospectively registered on 12 January 2015. Protocol V3 31 August 2015 with
      screening amended.

PMID- 29202863
TI  - A novel Family Dignity Intervention (FDI) for enhancing and informing holistic
      palliative care in Asia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The lack of a holistic approach to palliative care can lead to a
      fractured sense of dignity at the end of life, resulting in depression,
      hopelessness, feelings of being a burden to others, and the loss of the will to
      live among terminally ill patients. Building on the clinical foundation of
      Dignity Therapy, together with the empirical understanding of dignity-related
      concerns of Asian families facing terminal illness, a novel Family Dignity
      Intervention (FDI) has been developed for Asian palliative care. FDI comprises a
      recorded interview with a patient and their primary family caregiver, which is
      transcribed, edited into a legacy document, and returned to the dyads for sharing
      with the rest of the patient's family. The aims of this study are to assess the
      feasibility, acceptability and potential effectiveness of FDI in reducing
      psychosocial, emotional, spiritual, and psychophysiological distress in community
      dwelling and in-patient, Asian, older terminally ill patients and their families
      living in Singapore. METHODS/DESIGN: An open-label randomized controlled trial.
      One hundred and twenty-six patient-family dyads are randomly allocated to one of
      two groups: (1) an intervention group (FDI offered in addition to standard
      psychological care) and (2) a control group (standard psychological care). Both
      quantitative and qualitative outcomes are assessed in face-to-face interviews at
      baseline, 3 days and 2 weeks after intervention, as well as during an exit
      interview with family caregivers at 2 months post bereavement. Primary outcome
      measures include sense of dignity for patients and psychological distress for
      caregivers. Secondary outcomes include meaning in life, quality of life,
      spirituality, hopefulness, perceived support, and psychophysiological wellbeing,
      as well as bereavement outcomes for caregivers. Qualitative data are analyzed
      using the Framework method. DISCUSSION: To date, there is no available palliative
      care intervention for dignity enhancement in Asia. This first-of-its-kind study
      develops and tests an evidence-based, family driven, psycho-socio-spiritual
      intervention for enhancing dignity and wellbeing among Asian patients and
      families facing mortality. It addresses a critical gap in the provision of
      holistic palliative care. The expected outcomes will contribute to advancements
      in both theories and practices of palliative care for Singapore and its
      neighboring regions while serving to inform similar developments in other Asian
      communities. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03200730 . Registered
      on 26 June 2017.

PMID- 29202864
TI  - Consideration of non-canonical splice sites improves gene prediction on the
      Arabidopsis thaliana Niederzenz-1 genome sequence.
AB  - OBJECTIVE: The Arabidopsis thaliana Niederzenz-1 genome sequence was recently
      published with an ab initio gene prediction. In depth analysis of the predicted
      gene set revealed some errors involving genes with non-canonical splice sites in
      their introns. Since non-canonical splice sites are difficult to predict ab
      initio, we checked for options to improve the annotation by transferring
      annotation information from the recently released Columbia-0 reference genome
      sequence annotation Araport11. RESULTS: Incorporation of hints generated from
      Araport11 enabled the precise prediction of non-canonical splice sites. Manual
      inspection of RNA-Seq read mapping and RT-PCR were applied to validate the
      structural annotations of non-canonical splice sites. Predictions of untranslated
      regions were also updated by harnessing the potential of Araport11's information,
      which was generated by using high coverage RNA-Seq data. The improved gene set of
      the Nd-1 genome assembly (GeneSet_Nd-1_v1.1) was evaluated via comparison to the
      initial gene prediction (GeneSet_Nd-1_v1.0) as well as against Araport11 for the
      Col-0 reference genome sequence. GeneSet_Nd-1_v1.1 contains previously missed non
      canonical splice sites in 1256 genes. Reciprocal best hits for 24,527 (89.4%) of
      all nuclear Col-0 genes against the GeneSet_Nd-1_v1.1 indicate a high gene
      prediction quality.

PMID- 29202865
TI  - Prevalence and intensity of Schistosoma mansoni infections among schoolchildren
      attending primary schools in an urban setting in Southwest, Ethiopia.
AB  - OBJECTIVE: To determined both prevalence and intensity of Schistosoma mansoni
      infections among schoolchildren attending primary schools in Jimma town, an urban
      setting, Southwest, Ethiopia. RESULTS: The prevalence of S. mansoni infections
      was 8.4%. S. mansoni infections were found in all 17 schools, but the school
      prevalence ranged from 1.7 to 26.7%. This variation in prevalence could be
      explained by the proximity of the schools to the river crossing the town and
      water bodies near the schools. Boys were more infected compared to girls (chi 2 =
      31.587, P value = 0.001; 95% CI), and the infection rate increased as a function
      of age (chi 2 = 21.187; P value = 0.001; 95 %CI). The majority of the infection
      intensities were of low intensity (57%), the mean number of eggs per stool equal
      to 17 eggs per gram of stool. Based on the prevalence (8.4%) school children in
      Jimma Town is considered as a low risk of morbidity caused by S. mansoni
      (prevalence <= 10% according to WHO threshold), for which it is recommended to
      implement MDA once every 3 years which should be supplemented with health
      information to create awareness about Schistosomiasis transmission. Male students
      were more infected than females with majority of the infection intensity were
      low.

PMID- 29202866
TI  - Tracheostomy decannulation methods and procedures in adults: a systematic scoping
      review protocol.
AB  - BACKGROUND: The indications for and the number of tracheostomy procedures has
      increased with advances in critical care. Studies are indicating likely continued
      increase in number of tracheostomies. Despite the important benefits of a
      tracheostomy, its presence is associated with adverse health complications and
      lowered patient quality of life. Hence, it must be decannulated as soon as it is
      no longer indicated in a safe and effective manner. There is, however, no agreed
      universal standard of care for tracheostomy decannulation (TD) in adults. The
      aims of our study are to systematically map the literature on the decannulation
      process, reveal knowledge gaps and inform further research. METHODS: The search
      strategy of this systematic scoping review will involve the following electronic
      databases: PubMed/MEDLINE, Google Scholar, Union Catalogue of Theses and
      Dissertations (UCTD) via SABINET Online and WorldCat Dissertations and Theses via
      OCLC. Articles will also be searched through the "Cited by" search as well as
      citations included in the reference lists of included articles. Studies from the
      databases will be title screened and duplicates removed followed by a parallel
      two-independent reviewer screening of abstracts followed by full articles of
      selected studies both guided by eligibility criteria. We will extract data from
      the included studies and the emerging themes will be analysed. The relationship
      of the emerging themes to the research question will be critically examined. The
      quality of the included studies will be determined by Mixed Method Appraisal Tool
      (MMAT). We will use NVIVO version 10 to extract the relevant outcomes and
      thematic analysis of the studies. DISCUSSION: We anticipate to find studies that
      highlight evidence and preference as well as acceptability of TD methods and
      procedures. We hope to expose knowledge gaps and inform future research. Findings
      will be disseminated electronically, in print and through peer presentation,
      conferences and congresses. SYSTEMATIC REVIEW REGISTRATION: Our systematic review
      has been registered in PROSPERO: CRD42017072050 .

PMID- 29202867
TI  - Testing the 4Rs and 2Ss Multiple Family Group intervention: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Oppositional defiant disorder (ODD) is a major mental health concern
      and highly prevalent among children living in poverty-impacted communities.
      Despite that treatments for ODD are among the most effective, few children living
      in poverty receive these services due to substantial barriers to access, as well
      as difficulties in the uptake and sustained adoption of evidence-based practices
      (EBPs) in community settings. The purpose of this study is to examine
      implementation processes that impact uptake of an evidence-based practice for
      childhood ODD, and the impact of a Clinic Implementation Team (CIT)-driven
      structured adaptation to enhance its fit within the public mental health clinic
      setting. METHODS/DESIGN: This study, a Hybrid Type II effectiveness
      implementation research trial, blends clinical effectiveness and implementation
      research methods to examine the impact of the 4Rs and 2Ss Multiple Family Group
      (MFG) intervention, family level mediators of child outcomes, clinic/provider
      level mediators of implementation, and the impact of CITs on uptake and long-term
      utilization of this model. All New York City public outpatient mental health
      clinics have been invited to participate. A sampling procedure that included
      randomization at the agency level and a sub-study to examine the impact of clinic
      choice upon outcomes yielded a distribution of clinics across three study
      conditions. Quantitative data measuring child outcomes, organizational factors
      and implementation fidelity will be collected from caregivers and providers at
      baseline, 8, and 16 weeks from baseline, and 6 months from treatment completion.
      The expected participation is 134 clinics, 268 providers, and 2688
      caregiver/child dyads. We will use mediation analysis with a multi-level
      Structural Equation Modeling (SEM) (MSEM including family level variables,
      provider variables, and clinic variables), as well as mediation tests to examine
      study hypotheses. DISCUSSION: The aim of the study is to generate knowledge about
      effectiveness and mediating factors in the treatment of ODDs in children in the
      context of family functioning, and to propose an innovative approach to the
      adaptation and implementation of new treatment interventions within clinic
      settings. The proposed CIT adaptation and implementation model has the potential
      to enhance implementation and sustainability, and ultimately increase the extent
      to which effective interventions are available and can impact children and
      families in need of services for serious behavior problems. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT02715414 . Registered on 3 March 2016.

PMID- 29202869
TI  - Prognostic significance of hepatocyte growth factor activator inhibitor type 1
      (HAI-1) immunoreactivity in pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a
      membrane-bound serine protease inhibitor that is expressed on the surface of
      epithelial cells. Evidence has suggested that decreased cell surface HAI-1 in
      carcinoma cells results in enhanced invasiveness. However, little is known
      regarding the expression of HAI-1 in pancreatic ductal adenocarcinoma (PDAC).
      This study aimed to analyze HAI-1 expression in PDAC and its impact on patient
      prognosis. RESULTS: HAI-1 immunohistochemistry was performed on samples from 67
      PDAC cases. HAI-1 expression was increased in intraepithelial neoplasia compared
      to the adjacent non-neoplastic ductal epithelium. Of the 67 samples tested, 58%
      (39/67) of PDAC cases showed diffuse (> 75%) immunoreactivity in PDAC cells. The
      remaining cases showed reduced HAI-1 immunoreactivity in a substantial number of
      cancer cells. Although there was no correlation between HAI-1 status and tumor
      size, histologic grade or lymph node metastasis, diffuse HAI-1 positive cases
      showed longer disease-free survival (DFS; p = 0.006, log-rank test). In
      conclusion, HAI-1 is upregulated in pancreatic intraepithelial neoplasia and
      broadly expressed in PDAC cells. However, PDAC cases having areas of reduced HAI
      1 immunoreactivity may show shorter DFS.

PMID- 29202868
TI  - SP-A2 contributes to miRNA-mediated sex differences in response to oxidative
      stress: pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved.
AB  - BACKGROUND: Human innate host defense molecules, surfactant protein A1 (SP-A1),
      and SP-A2 differentially affect the function and proteome of the alveolar
      macrophage (AM). We hypothesized that SP-A genes differentially regulate the AM
      miRNome. METHODS: Humanized transgenic mice expressing SP-A1 and SP-A2 were
      subjected to O3-induced oxidative stress (OxS) or filtered air (FA), AMs were
      isolated, and miRNA levels were measured. RESULTS: In SP-A2 males, we found
      significant changes in miRNome in terms of sex and sex-OxS effects, with 11
      miRNAs differentially expressed under OxS. Their mRNA targets included BCL2, CAT,
      FOXO1, IL6, NF-kB, SOD2, and STAT3. We followed the expression of these
      transcripts as well as key cytokines, and we found that (a) the STAT3 mRNA
      significantly increased at 4 h post OxS and returned to baseline at 18 h post
      OxS. (b) The anti-oxidant protein SOD2 level significantly increased, but the CAT
      level did not change after 4 h post OxS compared to control. (c) The anti
      apoptotic BCL2 mRNA increased significantly (18 h post OxS), but the levels of
      the other transcripts were decreased. The presence of the SP-A2 gene had a
      protective role in apoptosis of AMs under OxS compared to mice lacking SP-A
      (knockout, KO). (d) Pro-inflammatory cytokine IL-6 protein levels were
      significantly increased in SP-A2 mice compared to KO (4 and 18 h post OxS), which
      signifies the role of SP-A2 in pro-inflammatory protein expression. (e) SOD2 and
      CAT mRNAs changed significantly in OxS indicating a plausible role of SP-A2 in
      the homeostasis of reactive oxygen species. (f) Gonadectomy of transgenic mice
      showed that sex hormones contribute to significant changes of the miRNome
      expression. CONCLUSIONS: We conclude that SP-A2 influences the miRNA-mediated sex
      specific differences in response to OxS. In males, these differences pertain to
      inflammatory, anti-apoptotic, and anti-oxidant pathways.

PMID- 29202870
TI  - Clinical predictors of chronic rhinosinusitis: do the Canadian clinical practice
      guidelines for acute and chronic rhinosinusitis predict CT-confirmation of
      disease?
AB  - BACKGROUND: The diagnosis of chronic rhinosinusitis (CRS) based on clinical
      presentation alone remains challenging. To improve the accuracy of clinical
      diagnosis, the Canadian Rhinosinusitis Guidelines recommend the use of specific
      symptom and endoscopic criteria. Our study objective was to determine whether
      symptom and endoscopic criteria, as defined by the Canadian Rhinosinusitis
      Guidelines, accurately predict CT-confirmed CRS diagnosis. METHODS: A
      retrospective cohort study of 126 patients who underwent CT sinuses based on
      clinical suspicion of possible CRS. The presence of symptom and endoscopic
      criteria, as defined by the Canadian Rhinosinusitis Guidelines, were compared
      between patients with and without a CT-confirmed CRS diagnosis using two-tailed
      Fisher's exact tests. Positive predictive values and likelihood ratios were
      determined for each symptom and endoscopic finding. RESULTS: Overall, 56.3% of
      patients had a CT-confirmed diagnosis of CRS. With the exception of nasal polyps,
      none of the symptom or endoscopic criteria had a statistically significant
      correlation with positive CT sinuses. For symptom criteria, positive predictive
      values ranged from 52.4% to 63.4%; likelihood ratios ranged from 0.85 to 1.34.
      For endoscopic criteria, positive predictive values and likelihood ratios were
      71.4% and 1.94 (edema); 63.0% and 1.32 (discharge); and 92.9% and 10.1 (nasal
      polyps). 35.2% of patients with CT-confirmed CRS had normal endoscopic exams.
      CONCLUSION: The Canadian Rhinosinusitis Guidelines' symptom and endoscopic
      criteria for CRS, with the exception of nasal polyps on endoscopy, do not
      accurately predict CT-confirmed disease. In addition, a normal endoscopic exam
      does not rule out CRS.

PMID- 29202871
TI  - Mesenchymal stem cell-derived extracellular vesicles for kidney repair: current
      status and looming challenges.
AB  - Novel therapies are urgently needed to address the rising incidence and
      prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD).
      Mesenchymal stem/stromal cells (MSCs) have shown promising results in
      experimental AKI and CKD, and have been used in the clinic for more than a decade
      with an excellent safety profile. The regenerative effects of MSCs do not rely on
      their differentiation and ability to replace damaged tissues, but are primarily
      mediated by the paracrine release of factors, including extracellular vesicles
      (EVs), composed of microvesicles and exosomes. MSC-derived EVs contain genetic
      and protein material that upon transferring to recipient cells can activate
      several repair mechanisms to ameliorate renal injury. Recent studies have shown
      that MSC-derived EV therapy improved renal outcomes in several animal models of
      AKI and CKD, including ischemia-reperfusion injury, drug/toxin-induced
      nephropathy, renovascular disease, ureteral obstruction, and subtotal
      nephrectomy. However, data about the renoprotective effects of EV therapy in
      patients with renal failure are scarce. This review summarizes current knowledge
      of MSC-derived EV therapy in experimental AKI and CKD, and discusses the
      challenges that need to be addressed in order to consider MSC-derived EVs as a
      realistic clinical tool to treat patients with these conditions.

PMID- 29202872
TI  - Patterns of HIV testing, drug use, and sexual behaviors in people who use drugs:
      findings from a community-based outreach program in Phnom Penh, Cambodia.
AB  - BACKGROUND: People who use drugs are an important priority for HIV programs.
      However, data related to their utilization of HIV services are limited. This
      paper reports patterns of HIV testing, drug use, and risk and service perception
      among people who use drugs. Study participants were receiving HIV and harm
      reduction services from a community-based program in Phnom Penh, comprised of
      itinerant peer-led outreach and static drop-in centers. METHODS: This was a mixed
      methods study conducted in 2014, comprising of a quantitative survey using a
      structured questionnaire, followed by two focus group discussions among a sub
      sample of survey participants. Participants were recruited from hotspots in five
      HIV high-burden communes using a two-stage cluster sampling method. Quantitative
      descriptive analyses and qualitative thematic analyses were performed. RESULTS:
      This study included 151 people who use drugs with a mean age of 31.2 (SD = 6.5)
      years; 77.5% were male and 39.1% were married. The most common drugs used were
      methamphetamines (72.8%) and heroin (39.7%), and 38.0% injected drugs in the past
      3 months. Overall, 83.3% had been tested for HIV in the past 6 months, of whom
      62.5% had been tested by peers through community-based outreach. However, there
      were ongoing HIV risks: 37.3% were engaging in sex on drugs, only 35.6% used a
      condom at last sexual intercourse, and 10.8% had had a sexually transmitted
      infection in the last 6 months. Among people who reported injecting drugs in the
      past 3 months, 27.5% reported re-using needles/syringes. Almost half (46.5%)
      perceived themselves as being at lower risk of HIV compared to the general
      population. Qualitative results contextualized the findings of low perception of
      HIV risks and suggested that although services were often unavailable on
      weekends, at night, or during national holidays, peer-led community-based
      outreach was highly accepted. CONCLUSIONS: A peer-led community-based approach
      was effective in reaching people who use drugs with HIV and harm reduction
      interventions. To mitigate ongoing HIV risks, expanding access to combination
      prevention interventions and implementing strategies to enable people who use
      drugs to objectively assess their HIV risks are required. Additionally, community
      based programs should collect data along the care continuum, to enable
      decentralized tracking of progress towards 90-90-90 goals at local levels.

PMID- 29202873
TI  - Gene expression in the chicken caecum is dependent on microbiota composition.
AB  - Gut microbiota is of considerable importance for each host. Despite this, germ
      free animals can be obtained and raised to sexual maturity and consequences of
      the presence or absence of gut microbiota on gene expression of the host remain
      uncharacterised. In this study, we performed an unbiased study of protein
      expression in the caecum of germ-free and colonised chickens. The major
      difference between these two groups was in the expression of immunoglobulins
      which were essentially absent in the germ-free chickens. Microbiota also caused a
      minor decrease in the expression of focal adhesion and extracellular matrix
      proteins and an increase in the expression of argininosuccinate synthase ASS1,
      redox potential sensing, fermentative metabolic processes and detoxification
      systems represented by sulfotransferases SULT1C3 or SULT1E1. Since we also
      analysed expression in the caecum of E. coli Nissle and E. faecium DSM7134 mono
      associated chickens, we concluded that at least immunoglobulin expression and
      expression of cystathionine synthase (CBS) was dependent on microbiota
      composition with E. coli Nissle stimulating more immunoglobulin and PIGR
      expression and E. faecium DSM7134 stimulating more CBS expression. Gut microbiota
      and its composition therefore affected protein expression in the chicken caecum
      though except for immunoglobulin production, the remaining differences were
      unexpectedly low.

PMID- 29202874
TI  - Sensitive detection of HIV-1 resistance to Zidovudine and impact on treatment
      outcomes in low- to middle-income countries.
AB  - BACKGROUND: Thymidine analogs, namely AZT (Zidovudine or RetrovirTM) and d4T
      (Stavudine or ZeritTM) are antiretroviral drugs still employed in over 75% of
      first line combination antiretroviral therapy (cART) in Kampala, Uganda despite
      aversion to prescribing these drugs for cART in high income countries due in part
      to adverse events. For this study, we explored how the continued use of these
      thymidine analogs in cART could impact emergence of drug resistance and impact on
      future treatment success in Uganda, a low-income country. METHODS: We examined
      the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients
      failing a first line combined antiretroviral treatment containing either AZT or
      d4T, which represents approximately 5% of the patients at the Joint Clinical
      Research Center receiving a AZT or d4T containing treatment. Next generation
      sequencing (DEEPGENTMHIV) and multiplex oligonucleotide ligation assays
      (AfriPOLA) were then performed on a subset of patient samples to detect low
      frequency drug resistant mutations. CD4 cell counts, viral RNA loads, and
      treatment changes were analyzed in a cohort of treatment success and failures.
      RESULTS: Over 80% of patients failing first line AZT/d4T-containing cART had
      predicted drug resistance to 3TC (Lamivudine) and non-nucleoside RT inhibitors
      (NNRTIs) in the treatment regimen but only 45% had resistance AZT/d4T associated
      resistance mutations (TAMs). TAMs were however detected at low frequency within
      the patients HIV quasispecies (1-20%) in 21 of 34 individuals who were failing
      first-line AZT-containing cART and lacked TAMs by Sanger. Due to lack of TAMs by
      Sanger, AZT was typically maintained in second-line therapies and these patients
      had a low frequency of subsequent virologic success. CONCLUSIONS: Our findings
      suggest that continued use of AZT and d4T in first-line treatment in low-to
      middle income countries may lead to misdiagnosis of HIV-1 drug resistance and
      possibly enhance a succession of second- and third-line treatment failures.

PMID- 29202875
TI  - Postoperative changes of the microbiome: are surgical complications related to
      the gut flora? A systematic review.
AB  - BACKGROUND: The purpose of this review was to identify the relationship between
      the gut microbiome and the development of postoperative complications like
      anastomotic leakage or a wound infection. Recent reviews focusing on underlying
      molecular biology suggested that postoperative complications might be influenced
      by the patients' gut flora. Therefore, a review focusing on the available
      clinical data is needed. METHODS: In January 2017 a systematic search was carried
      out in Medline and WebOfScience to identify all clinical studies, which
      investigated postoperative complications after gastrointestinal surgery in
      relation to the microbiome of the gut. RESULTS: Of 337 results 10 studies were
      included into this analysis after checking for eligibility. In total, the studies
      comprised 677 patients. All studies reported a postoperative change of the gut
      flora. In five studies the amount of bacteria decreased to different degrees
      after surgery, but only one study found a significant reduction. Surgical
      procedures tended to result in an increase of potentially pathogenic bacteria and
      a decrease of Lactobacilli and Bifidobacteria. The rate of infectious
      complications was lower in patients treated with probiotics/symbiotics compared
      to control groups without a clear relation to the systemic inflammatory response.
      The treatment with synbiotics/probiotics in addition resulted in faster recovery
      of bowel movement and a lower rate of postoperative diarrhea and abdominal
      cramping. CONCLUSIONS: There might be a relationship between the gut flora and
      the development of postoperative complications. Due to methodological
      shortcomings of the included studies and uncontrolled bias/confounding factors
      there remains a high level of uncertainty.

PMID- 29202876
TI  - Application of two-parameter scoliometer values for predicting scoliotic Cobb
      angle.
AB  - BACKGROUND: Adolescent idiopathic scoliosis, in which obvious curves are visible
      in radiographic images, is also seen in combination with lumps in the back. These
      lumps contribute to inclination, which can be measured by a scoliometer. To the
      authors' knowledge, there are no previous formulas combining thoracic and lumbar
      scoliometer values simultaneously to predict thoracic and lumbar Cobb angles,
      respectively. This study aimed to create more accurate two-parameter mathematical
      formulas for predicting thoracic and lumbar Cobb angles. METHODS: Between Dec.
      2012 and Jan. 2013, patients diagnosed with idiopathic scoliosis in an outpatient
      clinic were enrolled. The maximal trunk rotations at the thoracic and lumbar
      regions were recorded with a scoliometer. Right asymmetry hump was deemed
      positive (+), and left asymmetry hump was deemed negative (-). The Cobb angles
      were measured with a Picture Archiving and Communication System. Statistical
      analysis included Pearson's correlation coefficient, multivariate regression and
      Bland-Atman analysis. RESULTS: One-hundred and one patients were enrolled in our
      study. The average thoracic curve (TC) was 23.3 +/- 1.8 degrees , while the
      average lumbar curve (LC) was - 23.3 +/- 1.4 degrees . The thoracic inclination
      (TI) and lumbar inclination (LI) were 4.5 +/- 0.7 and - 5.9 +/- 0.6,
      respectively. The one-parameter formula for the thoracic curve was TC = 2.0 TI +
      14.3 (r = 0.813); for the lumbar curve, it was LC = 0.9 LI - 16.9 (r = 0.409). By
      multivariate regression, the two-parameter formulas for the thoracic and lumbar
      curves were TC = 2.6 TI - 1.4 LI (r = 0.931) and LC = - 1.5 TI + 2.0 LI (r =
      0.874), respectively. The two-parameter formulas were more accurate than the one
      parameter formulas. CONCLUSIONS: Based on the results of these two-parameter
      formulas for thoracic and lumbar curves, the Cobb angles can be predicted more
      accurately by the readings of the scoliometer. Physicians and other healthcare
      practitioners can thus evaluate patients with scoliosis more precisely than
      before with a scoliometer.

PMID- 29202877
TI  - Folate receptor-targeted molecular imaging improves identification of malignancy
      during pulmonary resection: a case report.
AB  - BACKGROUND: During minimally invasive pulmonary resection, both limited
      visualization and tactile feedback can make localization of pulmonary nodules and
      assessment for synchronous disease challenging. Intraoperative molecular imaging
      is an emerging technology that can enhance a surgeon's ability to detect cancers
      at the time of resection. CASE PRESENTATION: In this report, we describe the
      application of a folate receptor-targeted, near infrared optical contrast agent
      (OTL38) for the detection of an invasive pulmonary adenocarcinoma. During
      molecular imaging, an otherwise undetectable synchronous nodule was also
      identified. This finding resulted in intraoperative upstaging and operative plan
      modifications. CONCLUSION: This report marks the first successful utilization of
      a targeted, near infrared intraoperative molecular imaging probe useful for
      thoracic malignancies. This rapidly evolving technology may enhance the surgeon's
      ability to perform a number of oncologic procedures including tumor localization,
      margin assessment and intraoperative staging.

PMID- 29202878
TI  - Translation, cross-cultural adaptation and psychometric properties of the Nepali
      versions of numerical pain rating scale and global rating of change.
AB  - BACKGROUND: Pain intensity and patients' impression of global improvement are
      widely used patient-reported outcome measures (PROMs) in clinical practice and
      research. They are commonly assessed using the Numerical Pain Rating Scale (NPRS)
      and Global Rating of Change (GROC) questionnaires. The GROC is essential as an
      anchor for evaluating the psychometric properties of PROMs. Both of these PROMs
      are translated to many languages and have shown excellent psychometric
      properties. Their availability in Nepali would facilitate pain research and cross
      cultural comparison of research findings. Therefore, the objectives of this study
      were to translate and cross-culturally adapt the NPRS and GROC into Nepali and to
      assess the psychometric properties of the Nepali version of the NPRS (NPRS-NP).
      METHODS: After translating and cross-culturally adapting the NPRS and GROC into
      Nepali using recommended guidelines, NPRS-NP was administered to 104 individuals
      with musculoskeletal pain twice. The Nepali version of the GROC (GROC-NP) was
      administered at the follow-up for anchor-based assessment. (1) Test-retest
      reliability and minimum detectable change (MDC) among the stable group, (2)
      construct validity (by single sample t-test within the improved group and
      independent sample t-test between groups), and (3) concurrent validity were
      assessed. Receiver operating characteristic (ROC) curves were plotted to
      determine the responsiveness of the NPRS-NP using the area under the curve (AUC),
      and minimum important changes (MIC) for small, medium and large improvements.
      RESULTS: Significant cultural adaptations were required to obtain relevant Nepali
      versions of both the NPRS and GROC. The NPRS-NP showed excellent test-retest
      reliability and a MDC of 1.13 points. NPRS-NP demonstrated a good construct
      validity by significant within-group difference in mean of NPRS score- t(63)=
      7.57, P < 0.001 and statistically significant difference of mean score- t(98)= 
      4.24, P < .001 between the stable and improved groups. It demonstrated moderate
      concurrent correlation with the GROC-NP; r = 0.43, P < 0.01. Responsiveness of
      the NPRS-NP was shown at three levels with AUC = 0.68-0.82, and MIC = 1.17-1.33.
      CONCLUSIONS: The NPRS and GROC were successfully translated and culturally
      adapted into Nepali. The NPRS-NP demonstrated good reliability, validity and
      responsiveness in assessing musculoskeletal pain intensity in a Nepali
      population.

PMID- 29202879
TI  - The effect of prone and supine treatment positions for the pre-operative
      treatment of rectal cancer on organ-at-risk sparing and setup reproducibility
      using volumetric modulated arc therapy.
AB  - BACKGROUND AND PURPOSE: To compare organ-at-risk doses and setup reproducibility
      using the prone and supine orientations in volumetric modulated arc therapy
      (VMAT) for rectal cancer. MATERIALS AND METHODS: Seventeen consecutive rectal
      cancer patients undergoing preoperative radiation were selected and setup in
      either the prone (N = 8) or supine (N = 9) position. All patients were treated
      using posteriorly-applied VMAT. Bladder and small bowel dose and cone beam CT
      (CBCT) reproducibility metrics were retrospectively collected. RESULTS: Dose
      metrics for bladder and small bowel did not show significant differences between
      the prone and supine orientations. The prone data had a trend for smaller
      irradiated volumes than supine for the small bowel at lower doses-V20 (prone: 135
      +/- 99 cm3; supine: 201 +/- 162 cm3) and V30 (prone: 78 +/- 71 cm3; supine: 105
      +/- 106 cm3). At higher doses, the trend reversed as exemplified by the small
      bowel V50.4 (prone: 20 +/- 28 cm3; supine: 10 +/- 14 cm3). CBCT data showed that
      rotational errors in pitch and roll were significantly larger for the prone vs.
      supine orientation (pitch: 2.0 degrees  +/- 1.3 degrees  vs. 0.8 degrees  +/- 1.1
      degrees  p < 0.001; roll: 1.0 degrees  +/- 0.9 degrees  vs. 0.3 degrees  +/- 0.5
      degrees , p < 0.001). CONCLUSIONS: Bladder and small bowel doses were not
      significantly different when comparing VMAT plans developed for the prone and
      supine orientations. The supine orientation demonstrated improved setup
      reproducibility.

PMID- 29202880
TI  - A retrospective study on tuberculosis treatment outcomes at Jinka General
      Hospital, southern Ethiopia.
AB  - OBJECTIVE: Information on tuberculosis (TB) treatment outcomes would be useful
      for the improvement of the TB control program. The aim of the present study was
      to evaluate treatment outcomes of TB and identify associated factors in TB
      patients at the Jinka General Hospital (JGH), remote Zone of Ethiopia. RESULT:
      The result showed that 13.1% (154/1172) of the cases were cured, 60.9% treatment
      completed, 10.2% died and 9.1% were lost to follow-up. Thus, the overall
      treatment success rate was 74%. Male patients [AOR = 0.70 (0.52-0.93)] and HIV co
      infected patients [AOR = 0.67 (0.45-0.98)] were associated with unsuccessful
      treatment outcomes.

PMID- 29202881
TI  - Modifiable lifestyle risk factors for stroke among a high risk hypertensive
      population in Greater Kampala, Uganda; a cross-sectional study.
AB  - OBJECTIVE: To describe the modifiable lifestyle risk factors for stroke among a
      high risk population for stroke. Africa suffers from rapid population growth,
      adoption of harmful western diets, and increased prevalence of hypertension and
      obesity. RESULTS: A total of 440 study participants were screened and 87
      individuals with hypertension plus at least one other known stroke risk factor
      were enrolled. The prevalence of hypertension and diabetes mellitus in the
      screened population was 19.7 and 1.8%, respectively. Among those with
      hypertension only 2.3% (2/87) had ever had serum lipid assessment. Seventy-two
      percent (68/87) had very high serum LDL-cholesterol, while 33.3% (29/87) had low
      levels of HDL-cholesterol, and 67.8% had mean blood pressures greater than
      160/100 mmHg and 40% (35/87) were obese, with a BMI >=30. Targeting individuals
      with modifiable stroke risk factors and implementing self-management programs may
      be a way to reduce stroke burden in Uganda.

PMID- 29202882
TI  - Age and seasons influence on at-home pulse oximetry results in children evaluated
      for suspected obstructive sleep apnea.
AB  - BACKGROUND: Seasonal variability on obstructive sleep apnea has already been
      studied by polysomnography in children. Winter and spring season emerged as
      critical periods. No data are currently available for pulse oximetry performed at
      home. The aim of our study was to evaluate the effect of seasonality and age on
      the results of at-home pulse oximetry performed in children referred for
      suspected OSA. METHODS: We retrospectively studied 781 children (64.3% Males),
      aged 4.9 +/- 2.5 years. For all patients, we evaluated both pulse oximetry
      metrics and the McGill Oximetry Score. Variables for seasonal groups were
      assessed using Kruskal-Wallis test. A logistic regression model was performed to
      assess the relationship between patients' main characteristics, season period and
      the likelihood to have an abnormal McGill Oximetry Score. RESULTS: Patients
      recorded during winter were significantly younger (p < 0.02), nadir SpO2 was
      significantly lower (p < 0.002) and DI4 significantly higher than during others
      seasons (p < 0.005). Moreover, patients recorded during winter were nearly 2
      times more likely to have an abnormal MOS (aOR 1.949). The logistic regression
      showed that also younger age (p < 0.0001) was associated with a higher risk to
      find an abnormal pulse oximetry. CONCLUSIONS: In our study, the winter season
      confirms to be a critical period for pulse-oximetry and it should be taken into
      account by clinicians for a correct interpretation of tests. Our data show that
      also younger age affects the prevalence of abnormal at-home pulse oximetry in
      children.

PMID- 29202884
TI  - Do Experts Understand Performance Measures? A Mixed-Methods Study of Infection
      Preventionists.
AB  - : OBJECTIVE Central line-associated bloodstream infection (CLABSI) is associated
      with significant morbidity and mortality. Despite a nationwide decline in CLABSI
      rates, individual hospital success in preventing CLABSI is variable. Difficulty
      in interpreting and applying complex CLABSI metrics may explain this problem.
      Therefore, we assessed expert interpretation of CLABSI quality data. DESIGN:
      Cross-sectional survey PARTICIPANTS. Members of the Society for Healthcare
      Epidemiology of America (SHEA) Research Network (SRN) METHODS. We administered a
      10-item test of CLABSI data comprehension. The primary outcome was percent
      correct of attempted questions pertaining to the CLABSI data. We also assessed
      expert perceptions of CLABSI reporting. RESULTS The response rate was 51%
      (n=67).Among experts, the average proportion of correct responses was 73% (95%
      confidence interval [CI], 69%-77%). Expert performance on unadjusted data was
      significantly better than risk-adjusted data (86% [95% CI, 81%-90%] vs 65% [95%
      CI, 60%-70%]; P<.001). Using a scale of 1 to 100 (0, never reliable; 100, always
      reliable), experts rated the reliability of CLABSI data as 61. Perceived
      reliability showed a significant inverse relationship with performance (r=-0.28;
      P=.03), and as interpretation of data improved, perceptions regarding reliability
      of those data decreased. Experts identified concerns regarding understanding and
      applying CLABSI definitions as barriers to care. CONCLUSIONS Significant
      variability in the interpretation of CLABSI data exists among experts. This
      finding is likely related to data complexity, particularly with respect to risk
      adjusted data. Improvements appear necessary in data sharing and public policy
      efforts to account for this complexity. Infect Control Hosp Epidemiol 2018;39:71
      76.

PMID- 29202883
TI  - Sexual health, risky sexual behavior and condom use among adolescents young
      adults and older adults in Chiang Mai, Thailand: findings from a population based
      survey.
AB  - BACKGROUND: Sexual health is one of the key dimensions of health across all ages.
      Understanding risky sexual behaviors remains an important area of public health
      research. This study aimed to explore sexual health, risky sexual behaviors and
      factors associated with recent condom use as condom use is considered a main
      intervention proven to reduce negative health consequences of risky sexual
      behaviors, specifically related to sexually transmitted infections and unintended
      pregnancies. A stratified two-stage cluster sampling technique survey was
      conducted in Chiang Mai, Thailand. Information was obtained about age of first
      sexual intercourse, sexual activity, condom use, number of partners and history
      of drug/alcohol use prior to sexual activities within the past 3 months. A
      weighted analysis was performed to account for data clustering. RESULTS: It is
      estimated that most men (93%) and women (86%) in Chiang Mai have engaged in
      sexual intercourse. More than 70% of the people in Chiang Mai over age 30
      remained sexually active in the past 3 months, even for populations over age 50.
      Eight percent of male teenagers reported having more than one sexual partner in
      the past 3 months. Regular condom use was reported in less than 5% of the
      population (6.6% men and 3.1% women). CONCLUSIONS: Our study demonstrated that
      sexual health is an important public health issue across all age groups. Condom
      use has been promoted as one way to minimize and prevent unintended consequences
      of sexual behavior but overall use remains low.

PMID- 29202885
TI  - The COMMAND trial of cognitive therapy to prevent harmful compliance with command
      hallucinations: predictors of outcome and mediators of change.
AB  - BACKGROUND: Acting on harmful command hallucinations is a major clinical concern.
      Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR =
      0.45, 95% CI 0.23-0.88, p = 0.021). The focus of the therapy was a single
      mechanism, the power dimension of voice appraisal, was also significantly
      reduced. We hypothesised that voice power differential (between voice and voice
      hearer) was the mediator of the treatment effect. METHODS: The trial sample (n =
      197) was used. A logistic regression model predicting 18-month compliance was
      used to identify predictors, and an exploratory principal component analysis
      (PCA) of baseline variables used as potential predictors (confounders) in their
      own right. Stata's paramed command used to obtain estimates of the direct,
      indirect and total effects of treatment. RESULTS: Voice omnipotence was the best
      predictor although the PCA identified a highly predictive cognitive-affective
      dimension comprising: voices' power, childhood trauma, depression and self-harm.
      In the mediation analysis, the indirect effect of treatment was fully explained
      by its effect on the hypothesised mediator: voice power differential. CONCLUSION:
      Voice power and treatment allocation were the best predictors of harmful
      compliance up to 18 months; post-treatment, voice power differential measured at
      nine months was the mediator of the effect of treatment on compliance at 18
      months.

PMID- 29202886
TI  - Rhythm and rate control of atrial fibrillation in the emergency department - A
      large community-based observational study.
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia presentation to
      the emergency department (ED) and frequently results in admission to the
      hospital. Although rarely life-threatening and not usually an emergent condition,
      AF places a large burden on our health-care system. The objective of this study
      was to describe the practices of ED physicians in the management of AF in a large
      urban Canadian city. METHODS: From January 1, 2010 to December 31, 2010, patients
      with a primary diagnosis of AF were identified across 10 EDs in Toronto, Canada
      (N=2,609). Fifty patients were selected at random from each hospital for a
      detailed chart review (n=500). RESULTS: Two hundred thirty-two patients (46%)
      received rate control, and 129 (26%) received rhythm control with the remainder
      (28%) receiving neither therapy. Sixty-seven percent of patients were discharged
      home. Most patients (79%) were symptomatic on arrival; however, only a minority
      of these (31%) received rhythm control. Factors that were associated with rhythm
      control included younger age, duration of palpitations <= 48 hours, a lower
      CHADS2 score, and the absence of left ventricular dysfunction. CONCLUSION: Our
      data suggest a wide range of practice amongst ED physicians treating patients
      presenting to the ED with a primary diagnosis of AF. A randomized trial is needed
      to better understand the optimal management strategy in this patient population
      and setting.

PMID- 29202887
TI  - The effects of gelled konjac glucomannan fibre on appetite and energy intake in
      healthy individuals: a randomised cross-over trial.
AB  - Konjac glucomannan (KGM) is a viscous dietary fibre that can form a solid, low
      energy gel when hydrated and is commonly consumed in a noodle form (KGM-gel).
      Increased meal viscosity from gel-forming fibres have been associated with
      prolonged satiety, but no studies to date have evaluated this effect with KGM
      gel. Thus, our objective was to evaluate subsequent food intake and satiety of
      KGM-gel noodles when replacing a high-carbohydrate preload, in a dose-response
      manner. Utilising a randomised, controlled, cross-over design, sixteen healthy
      individuals (twelve females/four males; age: 26.0 (sd 11.8) years; BMI: 23.1 (sd
      3.2) kg/m2) received 325 ml volume-matched preloads of three KGM-gel noodle
      substitution levels: (i) all pasta with no KGM-gel (1849 kJ (442 kcal), control),
      half pasta and half KGM-gel (1084 kJ (259 kcal), 50-KGM) or no pasta and all KGM
      gel (322 kJ (77 kcal), 100-KGM). Satiety was assessed over 90 min followed by an
      ad libitum dessert. Compared with control, cumulative energy intake was 47 % (
      1761 kJ (-421 kcal)) and 23 % (-841 kJ (-201 kcal)) lower for 100-KGM and 50-KGM,
      respectively (both P<0.001), but no differences in subsequent energy intake was
      observed. Ratings of hunger were 31 % higher (P=0.03) for 100-KGM when compared
      with control, and were 19 % lower (P=0.04) for fullness and 28 % higher (P=0.04)
      for prospective consumption when comparing 100-KGM to 50-KGM. Palatability was
      similar across all treatments. Replacement of a high-carbohydrate preload with
      low-energy KGM-gel noodles did not promote additional food intake despite large
      differences in energy. The energy deficit incurred from partial KGM-gel
      substitution may have relevance in weight loss regimens, and should be further
      evaluated beyond the healthy population.

PMID- 29202888
TI  - Octreotide for the treatment of intentional insulin aspart overdose in a non
      diabetic patient.
AB  - Intentional insulin overdose may lead to severe and refractory hypoglycemia.
      Exogenous dextrose administration is the mainstay of therapy for these patients
      and is effective in most cases. However, in patients with a functional pancreas,
      exogenous dextrose administration may precipitate endogenous insulin release
      leading to rebound hypoglycemia. We describe a case report of a 41-year-old woman
      who injected 300 units of insulin aspart with suicidal intent. Her initial blood
      glucose was 2.3 mmol/L (41 mg/dL). Over the next 12 hours, she experienced
      recurrent hypoglycemic episodes despite 10% dextrose infusions and 14 ampoules of
      50% dextrose. Our patient experienced complications, including peripheral edema,
      related to the large volumes of intravenous dextrose required to attempt to
      maintain euglycemia. Octreotide, a somatostatin analogue, may help prevent
      dextrose-induced hypoglycemia and improve the management in select insulin
      overdose patients; large infusion volumes resulted in significant peripheral
      edema. Treatment with octreotide was initiated 12.5 hours post-injection and was
      followed by a stabilization of blood glucose concentration in this non-diabetic
      patient.

PMID- 29202889
TI  - Rapid protein disappearance rates along the small intestine advantage poultry
      performance and influence the post-enteral availability of amino acids.
AB  - A foundation diet, an intermediate blend and a summit diet were formulated with
      different levels of soyabean meal, casein and crystalline amino acids to compare
      'slow' and 'rapid' protein diets. The diets were offered to male Ross 308 chicks
      from 7 to 28 d post-hatch and assessed parameters included growth performance,
      nutrient utilisation, apparent digestibility coefficients and disappearance rates
      of starch and protein (N) in four small intestinal segments. Digestibility
      coefficients and disappearance rates of sixteen amino acids in three small
      intestinal segments and amino acid concentrations in plasma from portal and
      systemic circulations from the foundation and summit diets were determined. The
      dietary transition significantly accelerated protein (N) disappearance rates in
      the distal jejunum and ileum. The transition from foundation to summit diets
      significantly increased starch digestibility coefficients in the ileum and
      disappearance rates in all four small intestinal segments. These starch responses
      were associated with significant enhancements in nutrient utilisation. The
      dietary transition linearly increased digestibility coefficients and
      disappearance rates of amino acids in the majority of cases. The summit diet
      increased plasma concentrations of five amino acids but decreased those of four
      amino acids relative to the foundation diet to significant extents. Plasma
      concentrations of free amino acids were higher in the portal than systemic
      circulations. Rapid protein disappearance rates advantaged poultry performance
      and influenced post-enteral availability of amino acids. If the underlying
      mechanisms are to be identified, further research into the impact of protein
      digestive dynamics on broiler performance is required but appears justified.

PMID- 29202890
TI  - The validity of a web-based FFQ assessed by doubly labelled water and multiple 24
      h recalls.
AB  - The aim of this study was to validate the estimated habitual dietary intake from
      a newly developed web-based FFQ (WebFFQ), for use in an adult population in
      Norway. In total, ninety-two individuals were recruited. Total energy expenditure
      (TEE) measured by doubly labelled water was used as the reference method for
      energy intake (EI) in a subsample of twenty-nine women, and multiple 24-h recalls
      (24HR) were used as the reference method for the relative validation of
      macronutrients and food groups in the entire sample. Absolute differences,
      ratios, crude and deattenuated correlations, cross-classifications, Bland-Altman
      plot and plots between misreporting of EI (EI-TEE) and the relative misreporting
      of food groups (WebFFQ-24HR) were used to assess the validity. Results showed
      that EI on group level was not significantly different from TEE measured by
      doubly labelled water (0.7 MJ/d), but ranking abilities were poor (r -0.18). The
      relative validation showed an overestimation for the majority of the variables
      using absolute intakes, especially for the food groups 'vegetables' and 'fish and
      shellfish', but an improved agreement between the test and reference tool was
      observed for energy adjusted intakes. Deattenuated correlation coefficients were
      between 0.22 and 0.89, and low levels of grossly misclassified individuals (0-3
      %) were observed for the majority of the energy adjusted variables for
      macronutrients and food groups. In conclusion, energy estimates from the WebFFQ
      should be used with caution, but the estimated absolute intakes on group level
      and ranking abilities seem acceptable for macronutrients and most food groups.

PMID- 29202891
TI  - Impact of different approaches of primary care mental health on the prevalence of
      mental disorders.
AB  - : AimTo compare the impact of three different approaches to primary care mental
      health on the prevalence of mental disorders. BACKGROUND: Millions of people
      suffer from mental disorders. As entry point into the health service, primary
      healthcare plays an important role in providing mental health prevention and
      treatment. METHODS: Random sample of households in three different areas of the
      city of Ribeirao Preto (state of Sao Paulo, Brazil) were selected, and 20 trained
      medical students conducted interviews using a mental health screening instrument,
      the Mini-Screening of Mental Disorders, and a socio-demographic datasheet.
      Primary care mental health was provided in each area through a specific approach.
      The influence of the area of residence and the socio-demographic variables on the
      prevalence of mental disorder was explored and analyzed by univariate binary
      logistic regression and then by a multiple logistic regression model.FindingsA
      total of 1545 subjects were interviewed. Comparison between the three areas
      showed a significantly higher number of people with mental disorders in the area
      covered by the primary care team that did not have physicians with specific
      primary care mental health training, even when this association was adjusted for
      the influence of age, education, and socio-economic status.Our results suggest
      that residing in areas with family physicians with mental health training is
      associated with a lower prevalence of mental disorders.

PMID- 29202892
TI  - Risk Factors for Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae
      Carriage Upon Pediatric Intensive Care Unit Admission.

PMID- 29202893
TI  - The role of the early social environment on Epstein Barr virus infection: a
      prospective observational design using the Millennium Cohort Study.
AB  - : Epstein-Barr virus (EBV) is a highly prevalent herpesvirus linked to infectious
      mononucleosis and several malignancies. This paper aims to study the association
      between children's early life social environment at 9 months and EBV infection at
      3 years of age. METHODS: We used data on children included in the UK Millennium
      Cohort Study. We described the social environment using area-level and material
      factors as well as socioeconomic position (SEP) at 9 months. EBV was measured at
      3 years of age (n = 12 457). RESULTS: Lower rates of EBV infection were observed
      in children living in towns and rural areas compared with those living in cities.
      Lower SEP and overcrowding in the household increased the odds of being infected.
      Children whose parents were social tenants were more likely to be infected than
      homeowners. In the overall model, the strength of the association between
      material factors and EBV infection weakened. CONCLUSIONS: We showed that early
      life material deprivation was associated with a higher risk of EBV infection
      among 3-year-olds. Children living in more deprived social conditions may be more
      likely to become EBV carriers at an earlier age.

PMID- 29202894
TI  - Failure to detect the action of antidepressants in the forced swim test in Swiss
      mice.
AB  - OBJECTIVE: The aims of this study were to replicate previously published
      experiments and to modify the protocol to detect the effects of chronic
      antidepressant treatment in mice. METHODS: Male Swiss mice (n=6-8/group) housed
      in reversed light/dark cycle were randomly assigned into receive vehicle (10%
      sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30
      mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant,
      sodium butyrate (1-30 mg/kg) per gavage (p.o.) 1 h before the forced swim test
      (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2,
      respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or
      vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in
      reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST.
      Video recordings of behavioural testing were used for blind assessment of the
      outcomes. RESULTS: According to the expected, doses of antidepressants considered
      sub-effective failed to affect the immobility time of mice in the FST.
      Surprisingly, acute and chronic treatment with the high doses of bupropion,
      desipramine, and fluoxetine or sodium butyrate also failed to reduce the
      immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in
      the FST when injected i.p. or in mice housed in normal light/dark cycle.
      CONCLUSION: Data suggest the lack of efficacy of orally administered bupropion,
      desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high
      and low immobility mice, may explain the limited effects of the treatments.

PMID- 29202895
TI  - Bilateral ischaemic lesions of the medial prefrontal cortex are anxiogenic in the
      rat.
AB  - OBJECTIVE: Stroke patients often suffer from delayed disturbances of mood and
      cognition. In rodents, the prefrontal cortex (PFC) is involved in both higher
      order cognition and emotion. Our objective was to determine if bilateral focal
      ischaemic lesions restricted to the medial prefrontal cortex (mPFC) could be used
      to model post-stroke anxiety and/or cognitive deficits. METHODS: Groups of adult
      male Sprague-Dawley rats (n=9) received bilateral injections of either endothelin
      1 (ET-1) (400 pmol) or vehicle (artificial cerebrospinal fluid) into the mPFC and
      were tested at various times using both a test of temporal order memory and in an
      elevated plus maze. Lesions were verified histologically. RESULTS: ET-1 lesioned
      rats had reduced mobility on post-surgery day 8 that had resolved by day 29 at
      which time they spent significantly more time in the closed arm of the plus maze
      CONCLUSION: We conclude that ischaemic lesions localised to the mPFC can be used
      to model post-stroke anxiety in rats.

PMID- 29202896
TI  - Letter to the Editor: Affordable virtual reality tools for the treatment of
      mental health problems.

PMID- 29202897
TI  - Prevalence of MRSA ST398 Carriage in Nursing Home Residents in an Area of Spain
      With a High Density of Pig Farming.
AB  - MRSA nasal carriage was detected in 15.7% of 204 residents from 6 nursing homes
      (NHs) in the Osona region (Barcelona, Spain), and the MRSA-ST398 lineage was
      identified in 15.6% of MRSA-positive residents and in 2.5% of all NH residents
      evaluated. Most MRSA-ST398 carriers (4 of 5) had direct or indirect contact with
      pig farms. Infect Control Hosp Epidemiol 2018;39:90-93.

PMID- 29202898
TI  - Isolated psychosis during exposure to very high and extreme altitude -
      characterisation of a new medical entity.
AB  - BACKGROUND: Psychotic episodes during exposure to very high or extreme altitude
      have been frequently reported in mountain literature, but not systematically
      analysed and acknowledged as a distinct clinical entity. METHODS: Episodes
      reported above 3500 m altitude with possible psychosis were collected from the
      lay literature and provide the basis for this observational study. Dimensional
      criteria of the Diagnostic and Statistical Manual of Mental Disorders were used
      for psychosis, and the Lake Louise Scoring criteria for acute mountain sickness
      and high-altitude cerebral oedema (HACE). Eighty-three of the episodes collected
      underwent a cluster analysis to identify similar groups. Ratings were done by two
      independent, trained researchers (kappa values 0.6-1).FindingsCluster 1 included
      51% (42/83) episodes without psychosis; cluster 2 22% (18/83) cases with
      psychosis, plus symptoms of HACE or mental status change from other origins; and
      cluster 3 28% (23/83) episodes with isolated psychosis. Possible risk factors of
      psychosis and associated somatic symptoms were analysed between the three
      clusters and revealed differences regarding the factors 'starvation' (chi2 test,
      p = 0.002), 'frostbite' (p = 0.024) and 'supplemental oxygen' (p = 0.046).
      Episodes with psychosis were reversible but associated with near accidents and
      accidents (p = 0.007, odds ratio 4.44). CONCLUSIONS: Episodes of psychosis during
      exposure to high altitude are frequently reported, but have not been specifically
      examined or assigned to medical diagnoses. In addition to the risk of suffering
      from somatic mountain illnesses, climbers and workers at high altitude should be
      aware of the potential occurrence of psychotic episodes, the associated risks and
      respective coping strategies.

PMID- 29202899
TI  - Assessment of Recovery of Milk Protein Allergens from Processed Food for Mass
      Spectrometry Quantification.
AB  - Assessing the recovery of food allergens from solid processed matrixes is one of
      the most difficult steps that needs to be overcome to enable the accurate
      quantification of protein allergens by immunoassay and MS. A feasibility study is
      described herein applying International System of Units (SI)-traceably quantified
      milk protein solutions to assess recovery by an improved extraction method.
      Untargeted MS analysis suggests that this novel extraction method can be further
      developed to provide high recoveries for a broad range of food allergens. A
      solution of alpha-casein was traceably quantified to the SI for the content of
      alpha-S1 casein. Cookie dough was prepared by spiking a known amount of the SI
      traceable quantified solution into a mixture of flour, sugar, and soya spread,
      followed by baking. A novel method for the extraction of protein food allergens
      from solid matrixes based on proteolytic digestion was developed, and its
      performance was compared with the performance of methods reported in the
      literature.

PMID- 29202900
TI  - Food Allergen Labeling: A Latin American Approach.
AB  - Food allergy is a public health concern almost all over the world. Although most
      of the countries that regulate the declaration of allergens in prepackaged foods
      include the list recommended by the Codex Alimentarius, some countries have added
      other allergens to this list due to prevalence data and regional incidence,
      whereas others have incorporated exceptions for some products derived from
      allergenic foods. Within this context, the situation in Latin America regarding
      these regulations is diverse. Data about prevalence of food hypersensitivity are
      very limited in the region. The countries that have established regulations are
      Brazil, Colombia, Costa Rica, Guatemala, Honduras, El Salvador, Nicaragua, Chile,
      Mexico, and Venezuela. Argentina has approved a regulation for the labeling of
      food allergens in November 2016. It only needs to be published in the Official
      Bulletin to go into effect. All countries follow the Codex list that includes
      latex and excludes sulfites, except Brazil. On the other hand, Argentina is the
      only country that includes exceptions. As for the methodologies for the detection
      of allergens in foods, this issue is a serious problem for both the food industry
      and control laboratories. Available methodologies are based mainly on commercial
      ELISA kits; currently, there are no Latin American companies that produce them,
      so ELISA kits are expensive and their acquisition is complicated. There is an
      initiative in Argentina to address all these gaps in the region through the
      Platform of Food Allergens (PFA), a nonprofit organization that integrates health
      professionals, patients, representatives of the food industry, government, and
      scientists. The different actions carried out by the PFA have made it possible to
      contact different scientific groups from other Latin American countries in order
      to expand this initiative and thereby promote and strengthen both public and
      private capacities in the region.

PMID- 29202901
TI  - European Regulations for Labeling Requirements for Food Allergens and Substances
      Causing Intolerances: History and Future.
AB  - Food allergens and intolerances have been diagnosed by doctors for decades, but
      have received heightened attention in the last two decades because diagnosis and
      awareness have increased. Consequently, regulators in many jurisdictions have
      addressed this topic by introducing labeling requirements for substances causing
      allergies and intolerance reactions in affected individuals. Mandatory labeling
      of food allergens allows persons suffering from these to make informed choices.
      However, regulations in some geographic areas have resulted in significant
      problems for manufacturers as well as consumers. This has been mainly due to
      frequent changes and amendments, and it has been difficult for all stakeholders
      to follow and understand the status quo of legislation. The present paper
      describes the development of European directives and regulations for the labeling
      of food allergens and intolerances to substances like gluten over the past
      decades and provides an outlook of what can reasonably be expected to change in
      the coming years. It also identifies existing gaps, like a lack of threshold
      levels for adventitious contamination and consequently a proliferation of
      precautionary allergen labeling, which neither benefits the consumer nor the food
      industry in its current form.

PMID- 29202902
TI  - Action Levels for Food Allergens: An Approach for Official Food Control in
      Germany.
AB  - Official food control laboratories in Germany have established internal action
      values for the assessment of analytical results of food allergens especially
      obtained from samples without declaration of the specified allergen. A pragmatic
      approach was chosen considering the current situation for European food
      information legislation. Accordingly, when a positive result is obtained for an
      unlabeled allergen, it is not necessarily an irregularity if it can be
      demonstrated that the result was caused by cross-contamination. Action values
      take into account current analytical experiences as well as published
      allergologic reference doses. They are considered as internal de minimis
      thresholds by food control authorities that are used to support laboratories in
      the decision-making process and when a written expert opinion is requested by an
      enforcement authority. If only minor traces are detected at concentrations below
      the action values, further investigation of the issue and inspections at the
      location of manufacture can be abandoned. The present report includes a
      collection of results from official food control laboratories in Germany that
      have been evaluated in line with the aforementioned system of action levels.

PMID- 29202903
TI  - Food Allergen Management in Australia.
AB  - Food allergies are increasing globally, including numbers of allergens, the
      sensitization rate, and the prevalence rate. To protect food-allergic individuals
      in the community, food allergies need to be appropriately managed. This paper
      describes current Australian food allergen management practices. In Australia,
      the prevalence of food allergies, the anaphylaxis rate, and the fatal anaphylaxis
      rate are among the highest in the world. Interagency and stakeholder
      collaboration is facilitated and enhanced as Australia moves through past,
      current, and ongoing food allergen challenges. As a result, Australia has been a
      global leader in regulating the labeling of common allergens in packaged foods
      and their disclosure in foods not required to bear a label. Moreover, the food
      industry in Australia and New Zealand has developed a unique food allergen risk
      management tool, the Voluntary Incidental Trace Allergen Labelling program, which
      is managed by the Allergen Bureau. This paper summarizes insights and information
      provided by the major stakeholders involved to protect food-allergic consumers
      from any allergic reaction. Stakeholders include government; consumer protection,
      regulation, and enforcement agencies; the food industry; and food allergen
      testing and food allergen/allergy research bodies in Australia. The ongoing goal
      of all stakeholders in food allergen management in Australia is to promote best
      practice food allergen management procedures and provide a wide choice of foods,
      while enabling allergic consumers to manage their food allergies and reduce the
      risk of an allergic reaction.

PMID- 29202904
TI  - A Global Reflection on Food Allergen Regulations, Management, and Analysis.

PMID- 29202905
TI  - Undeclared Food Allergens and Gluten in Commercial Food Products Analyzed by
      ELISA.
AB  - Undeclared allergen(s) in commercial food products are responsible for many food
      recalls, as reported by regulatory agencies in various countries, including the
      United States. Correct allergen labeling practices are essential for the safety
      of food-allergic consumers. However, this practice may be hindered by the
      introduction of allergens all along the food supply chain, including
      unintentionally through cross-contact. To understand the pervasiveness of
      undeclared allergen(s) in commercial food products, the objective of this review
      is to summarize the prevalence of undeclared milk, egg, hazelnut, peanut, soy,
      and gluten as detected by ELISA from previously published surveys. The prevalence
      of undeclared allergen(s) in products with or without an advisory statement was
      also summarized and compared. As compiled by this review, there are some food
      categories that may be at higher risk for containing undeclared allergen(s).
      However, the data on prevalence and amount of allergen present may vary widely
      within any particular allergen or food category. Factors, such as food survey
      product selection, geography, awareness of allergen/gluten issues, and/or the
      choice of ELISA method, may be responsible for such differences.

PMID- 29202906
TI  - Managing Food Allergens in the U.K. Retail Supply Chain.
AB  - The U.K. food and grocery market is highly significant financially and dominated
      by 10 retailers within a regulated and extremely economically competitive
      environment. We summarize the approach of U.K. retailers to allergen risk
      assessment (RA) and risk management (RM) within the U.K. legal framework and
      explore public visibility of retailers' allergen policies. RA and RM of allergens
      appear effective in curtailing retail-triggered severe food allergy reactions.
      However, allergen recalls remain high, precautionary allergen labeling (PAL)
      remains an area of confusion, and there is no consistent Web-based provision of
      information for consumers who have allergies. Resolution of PAL awaits an agreed
      on threshold framework, but a key challenge is to engage with patients and gain
      their trust rather than thrust education at them. It would be helpful for
      retailers to publish their allergen RA and RM policies. A target should be agreed
      on between government and retailers for a reduction in the proliferation of PAL
      wording variants by a given date within the next 3 years. A further hurdle is
      potentially flawed allergen analysis-development of reference methods and
      reference materials are acknowledged needs. Laboratories should report allergen
      results in an informative manner, communicating uncertainty and caveats. Ideally
      a laboratory representative would be included on any incident control team.
      Efforts must continue to standardize preparedness for protecting and defending
      food and drink from deliberate attack.

PMID- 29202907
TI  - Challenges and Path Forward on Mandatory Allergen Labeling and Voluntary
      Precautionary Allergen Labeling for a Global Company.
AB  - For food manufacturers, the label on a food package is a tool meant to alert
      consumers to the presence of specific allergens, allowing consumers to make
      informed decisions and not unnecessarily limit their food choices. Mandatory
      allergen labeling is used when the allergen is an intentionally added ingredient,
      whereas voluntary allergen labeling is used when the presence of the allergen is
      unintentional and may be in the finished product as a result of cross-contact. In
      a globalized economy, ensuring food safety is a growing challenge for
      manufacturers. When ingredients and technologies are sourced worldwide from
      multiple business partners, complexity rises, which can increase the chance for
      errors, leading to potential harm. Threshold science, Voluntary Incidental Trace
      Allergen Labelling (VITAL) reference doses, fit-for-purpose analytical
      technology, and common sense enable us to optimize allergen management for the
      benefit of allergic consumers. This is a good strategy because all stakeholders
      share the common goal of making foods safe and wholesome for all. Herein, we
      recommend that (1) senior management make science-based thresholds a priority for
      both regulatory authorities and the food industry; (2) VITAL 2.0 be adopted as a
      risk assessment and risk management tool for precautionary allergen labeling
      (PAL); (3) a standardized message for PAL, i.e., "may contain x," be used to make
      it easily understandable to allergic consumers so they can make informed food
      choices; and (4) validated fit-for-purpose allergen methods be used to meet
      analytical needs. This is an opportunity for us to speak with one voice and
      demonstrate that food safety is not a competitive issue, but a shared
      responsibility. This approach could significantly improve allergic consumers'
      lives.

PMID- 29202908
TI  - Japanese Food Allergen Labeling Regulation: An Update.
AB  - The Japanese food allergen labeling regulation was designed to match real
      Japanese food allergy circumstances and also to be enforced effectively; thus,
      (1) regulated food allergens were selected by prevalence and seriousness
      according to food allergy surveys in Japan; (2) the detection criterion for ELISA
      monitoring, 10 MUg food allergen protein/g (or mL) food, was set up as the
      threshold value to regulate commercial prepackaged foods; and (3) official food
      allergen analytical methods, which can determine the threshold value accurately,
      were developed. These three points are distinctive from other countries.
      Furthermore, as an on-going project, the regulation has been amended according to
      food allergy circumstances and requirements of society. This paper presents
      recent changes regarding the Japanese food allergen labeling regulation. To date,
      the Japanese food allergen labeling regulation has been enforced for more than 15
      years and seems to be working effectively. Now would be an opportune time to
      review the regulation for its next level of development.

PMID- 29202909
TI  - Commercial ELISA Measurement of Allergens and Gluten: What We Can Learn from Case
      Studies.
AB  - During the last decade, results from ELISA test kits have often been criticized
      as being flawed. Therefore, it may appear counterintuitive that ELISAs are used
      for most food allergen and gluten analytical needs. One reason, in addition to
      the nonavailability of comparable alternative methods, is the fact that the
      methods used underwent a long validation and learning period in the market. This
      publication presents several case studies on interference, cross-reactivity
      issues, calibrators, fragmented allergens and gluten, matrix influences, and
      misunderstood intended-use statements. Afterward, the relevant validation
      parameter LOD, LOQ, selectivity, and precision are discussed. Finally, a
      comprehensive list of practical recommendations for ELISA test kit users is
      presented.

PMID- 29202910
TI  - A Targeted LC-MS/MS Method for the Simultaneous Detection and Quantitation of
      Egg, Milk, and Peanut Allergens in Sugar Cookies.
AB  - Food allergy is a growing public health concern, with many individuals reporting
      allergies to multiple food sources. Compliance with food labeling regulations and
      prevention of inadvertent cross-contact in manufacturing requires the use of
      reliable methods for the detection and quantitation of allergens in processed
      foods. In this work, a novel liquid chromatography-tandem mass spectrometry
      multiple-reaction monitoring method for multiallergen detection and quantitation
      of egg, milk, and peanut was developed and evaluated in an allergen-incurred
      baked sugar cookie matrix. A systematic evaluation of method parameters,
      including sample extraction, concentration, and digestion, were optimized for
      candidate allergen peptide markers. The optimized method enabled the reliable
      detection and quantitation of egg, milk, and peanut allergens in sugar cookies,
      with allergen concentrations as low as 5 ppm allergen-incurred ingredient.

PMID- 29202911
TI  - The Allergen Bureau VITAL Program.
AB  - This paper sets out the role of the Allergen Bureau and the Voluntary Incidental
      Trace Allergen Labelling (VITAL) Program from its origin in 2007 to its current
      iteration, VITAL 2. Herewith are outlined the scientific principles that support
      the program; the program's application in the food chain; and the benefits of the
      program's use to the food industry, clinicians, and the allergic consumer. VITAL
      was developed by the Australian and New Zealand food industry in consultation
      with multiple stakeholders, including consumer organizations, industry bodies,
      regulators, and retailers, to provide a standardized, science-based risk
      assessment process for the investigation of the potential presence of food
      allergens due to cross-contact and to determine whether, for cases in which the
      allergen is unable to be removed or controlled consistently, precautionary
      statements are required. The aim of the program is to provide a consistent
      process, a standardized approach, and a relevant cross-contact statement to allow
      the allergic consumer to make an informed decision regarding consumption of food.

PMID- 29202912
TI  - Assessing Almond and Peanut Allergens Using Commercially Available
      Immunoanalytical Kits and LC-MS/MS: A Case Study.
AB  - With an ever-increasing allergic population and an emerging market for allergen
      free foods, accurate detection of allergens in foods has never been more
      important. Although ELISA-based methods are the most widely used for detection of
      allergens in food, there is a need for the development of orthogonal approaches.
      A commercial ELISA detected a relatively high concentration of peanut and almond
      in an allergen-free product. However, another commercial ELISA declared a low
      peanut concentration and was negative for almond. Further testing using a
      commercial almond lateral-flow device confirmed the results from the second ELISA
      kit and demonstrated that the positive detection of almond was due to cross
      reactivity. An MS method was used for final confirmation that the reported
      results were negative for both almond and peanut.

PMID- 29202913
TI  - ILSI Europe's Food Allergy Task Force: From Defining the Hazard to Assessing the
      Risk from Food Allergens.
AB  - The International Life Sciences Institute (ILSI) Europe Food Allergy Task Force
      was founded in response to early public concerns about the growing impact of food
      allergies almost coincidentally with the publication of the 1995 Food and
      Agriculture Organization-World Health Organization Technical Consultation on Food
      Allergies. In line with ILSI principles aimed to foster collaboration between
      stakeholders to promote consensus on science-based approaches to food safety and
      nutrition, the task force has played a central role since then in the development
      of risk assessment for food allergens. This ranged from consideration of the
      criteria to be applied to identifying allergens of public health concern through
      methodologies to determine the relationship between dose and the proportion of
      allergic individuals reacting, as well as the nature of the observed responses.
      The task force also promoted the application of novel, probabilistic risk
      assessment methods to better delineate the impact of benchmarks, such as
      reference doses, and actively participated in major European food allergy
      projects, such as EUROPREVALL, the European Union (EU)-funded project "The
      prevalence, cost and basis of food allergy across Europe;" and iFAAM, "Integrated
      approaches to food allergen and allergy risk management," also an EU-funded
      project. Over the years, the task force's work has evolved as answers to initial
      questions raised further issues: Its current work program includes a review of
      analytical methods and how different ones can best be deployed given their
      strengths and limitations. Another activity, which has just commenced, aims to
      develop a framework for stakeholders to achieve consensus on acceptable risk.

PMID- 29202914
TI  - Integrating Allergen Analysis Within a Risk Assessment Framework: Approaches to
      Development of Targeted Mass Spectrometry Methods for Allergen Detection and
      Quantification in the iFAAM Project.
AB  - Allergen analysis is central to implementing and monitoring food allergen risk
      assessment and management processes by the food industry, but current methods for
      the determination of allergens in foods give highly variable results. The
      European Union-funded "Integrated Approaches to Food Allergen and Allergy Risk
      Management" (iFAAM) project has been working to address gaps in knowledge
      regarding food allergen management and analysis, including the development of
      novel MS and immuno-based allergen determination methods. Common allergenic food
      ingredients (peanut, hazelnut, walnut, cow's milk [Bos domesticus], and hen's egg
      [Gallus domesticus]) and common food matrixes (chocolate dessert and cookie) have
      been used for both clinical studies and analytical method development to ensure
      that the new methods are clinically relevant. Allergen molecules have been used
      as analytical targets and allergenic ingredients incurred into matrixes at levels
      close to reference doses that may trigger the use of precautionary allergen
      labeling. An interlaboratory method comparison has been undertaken for the
      determination of peanut in chocolate dessert using MS and immuno-based methods.
      The iFAAM approach has highlighted the need for methods to report test results in
      allergenic protein. This will allow food business operators to use them in risk
      assessments that are founded on clinical study data in which protein has been
      used as a measure of allergenic potency.

PMID- 29202915
TI  - Novel Approaches for the MS-Based Detection of Food Allergens: High Resolution,
      MS3, and Beyond.
AB  - The prevalence of allergic reactions to food is believed to be increasing in
      industrialized countries worldwide. One of the major tasks in risk management is,
      therefore, the analytical surveillance of allergen contamination in food and
      targeted proteomics using MS, which is of hugely growing interest due to its
      specificity and sensitivity and the possibility to analyze multiple allergens in
      parallel. Though approximately 200 different foods have been described as having
      the potential to elicit allergic reactions, current regional labeling
      requirements are focused on the 5-14 priority allergens that elicit the vast
      majority of severe reactions or that pose a risk as hidden allergens in food
      production. MS-based detection methods have been published for the majority of
      priority allergens, and this review provides an overview of the different
      methodological approaches, namely multiple-reaction monitoring-, high-resolution
      MS-, and triple-stage MS-based methods. In addition, requirements for the
      identification and validation of specific marker peptides and the influence of
      thermal processing and structural heterogeneity of allergens are discussed.

PMID- 29202916
TI  - The Use of Visual Examination for Determining the Presence of Gluten-Containing
      Grains in Gluten Free Oats and Other Grains, Seeds, Beans, Pulses, and Legumes.
AB  - Obtaining representative test samples for antibody-based testing is challenging
      when analyzing whole grains for gluten. When whole grains are ground into flour
      for testing, confocal microscopy studies have shown that gluten tends to exist as
      aggregates within the starch background, making single-sample testing inaccurate
      and complicating the ability to arrive at an accurate average from multiple
      samples. In addition, whole-grain products present a unique risk to gluten free
      consumers, in that any contamination is localized to specific servings rather
      than being distributed across the product lot. This makes parts-per-million
      values less relevant for whole-grain products. Intact grains, seeds, beans,
      pulses, and legumes offer an alternative opportunity for gluten detection, in
      that contaminating gluten-containing grains (GCGs) are visible and identifiable
      to the trained eye or properly calibrated optical sorting equipment. The purpose
      of the current study was to determine a Gluten Free Certification Organization
      threshold level for the maximum number of GCGs within a kilogram of nongluten
      grains sold as specially processed gluten free product and to determine the
      feasibility of this threshold by evaluating visual examination data from two
      major oat processors.

PMID- 29202917
TI  - Development and Validation of a Quantitative ELISA for the Detection of Almond
      Residues in Foods.
AB  - Neogen Corp. has developed Veratox for Almond Allergen for use in the
      quantitative analysis and screening of almond protein residues in food products,
      such as cookies, crackers, chocolate bars, cereals, beverages, and clean-in-place
      rinses. Quantitation with Veratox for Almond Allergen ranges from 2.5 to 25 ppm
      and, with dilution, it can be extended for highly positive samples. This paper
      describes the findings of internal testing and validation studies designed to
      establish product claims for the assay of Veratox for Almond Allergen.

PMID- 29202918
TI  - Almond or Mahaleb? Orthogonal Allergen Analysis During a Live Incident
      Investigation by ELISA, Molecular Biology, and Protein Mass Spectrometry.
AB  - It is now well known that an incident investigated in the United Kingdom in 2015
      of cumin alleged to be contaminated with almond, a risk for people with almond
      allergy, was caused by the Prunus species, Prunus mahaleb. In the United Kingdom,
      the Government Chemist offers a route of technical appeal from official findings
      in the food control system. Findings of almond in two official samples, cumin and
      paprika, which had prompted action to exclude the consignments from the food
      chain, were so referred. Herein are described the approaches deployed to resolve
      the analytical issues during the investigation of the incidents. The cross
      reactivity of ELISA to Prunus species was confirmed, and although this is useful
      in screening for the genus, orthogonal techniques are required to identify the
      species and confirm its presence. Two novel PCR assays were developed: one
      specific for P. mahaleb and the other a screening method capable of identifying
      common Prunus DNA. Peptides unique to almond and mahaleb were identified,
      permitting LC-tandem MS and criteria were developed for peptide identification to
      forensic standards. This work enables a staged approach to be taken to any future
      incident thought to involve Prunus species and provides a template for the
      investigation of similar incidents.

PMID- 29202919
TI  - Stakeholders' Guidance Document for Consumer Analytical Devices with a Focus on
      Gluten and Food Allergens.
AB  - Until recently, analytical tests for food were performed primarily in
      laboratories, but technical developments now enable consumers to use devices to
      test their food at home or when dining out. Current consumer devices for food can
      determine nutritional values, freshness, and, most recently, the presence of food
      allergens and substances that cause food intolerances. The demand for such
      products is driven by an increase in the incidence of food allergies, as well as
      consumer desire for more information about what is in their food. The number and
      complexity of food matrixes creates an important need for properly validated
      testing devices with comprehensive user instructions (definitions of technical
      terms can be found in ISO 5725-1:1994 and the International Vocabulary of
      Metrology). This is especially important with food allergen determinations that
      can have life-threatening consequences. Stakeholders-including food regulators,
      food producers, and food testing kit and equipment manufacturers, as well as
      representatives from consumer advocacy groups-have worked to outline voluntary
      guidelines for consumer food allergen- and gluten-testing devices. These
      guidelines cover areas such as kit validation, user sampling instructions, kit
      performance, and interpretation of results. The recommendations are based on (1)
      current known technologies, (2) analytical expertise, and (3) standardized AOAC
      INTERNATIONAL allergen community guidance and best practices on the analysis of
      food allergens and gluten. The present guidance document is the first in a series
      of papers intended to provide general guidelines applicable to consumer devices
      for all food analytes. Future publications will give specific guidance and
      validation protocols for devices designed to detect individual allergens and
      gluten, as statistical analysis and review of any validation data, preferably
      from an independent third party, are necessary to establish a device's fitness
      for-purpose. Following the recommendations of these guidance documents will help
      ensure that consumers are equipped with sufficient information to make an
      informed decision based on an analytical result from a consumer device. However,
      the present guidance document emphasizes that consumer devices should not be used
      in isolation to make a determination as to whether a food is safe to eat. As
      advances are made in science and technology, these recommendations will be
      reevaluated and revised as appropriate.

PMID- 29202920
TI  - Target Selection Strategies for LC-MS/MS Food Allergen Methods.
AB  - The detection and quantitation of allergens as contaminants in foods using MS is
      challenging largely due to the requirement to detect proteins in complex, mixed,
      and often processed matrixes. Such methods necessarily rely on the use of
      proteotypic peptides as indicators of the presence and amount of allergenic
      foods. These peptides should represent the allergenic food in question in such a
      way that their use is both sensitive (no false-negatives) and specific (no false
      positives). Choosing such peptides to represent food allergens is beset with
      issues, including, but not limited to, separated ingredients (e.g., casein and
      whey), extraction difficulties (particularly from thermally processed foods), and
      incomplete sequence information, as well as the more common issues associated
      with protein quantitation in biological samples. Here, we review the workflows
      that have been used to select peptide targets for food allergen detection. We
      describe the use and limitations of both in silico-based analyses and
      experimental methods relying on high-resolution MS. The variation in the way in
      which target selection is performed highlights a lack of standardization, even
      around the principles describing what the detection method should achieve. A lack
      of focus on the food matrixes to which the method will be applied is also
      apparent during the peptide target selection process. It is hoped that
      highlighting some of these issues will assist in the generation of MS-based
      allergen detection methods that will encourage uptake and use by the analytical
      community at large.

PMID- 29202921
TI  - Highly Sensitive Matrix-Independent Quantification of Major Food Allergens Peanut
      and Soy by Competitive Real-Time PCR Targeting Mitochondrial DNA.
AB  - The development of two competitive real-time PCR assays for the quantitative
      detection of trace amounts of two major food allergens, peanut and soybean, is
      reported. In order to achieve very low detection levels for both allergens, we
      established PCR primers and probes targeting mitochondrial DNA sequences. We were
      able to demonstrate that this approach led to an increase in detection
      sensitivity in the range of at least 1 order of magnitude compared with published
      assays targeting nuclear DNA. Furthermore, we generated corresponding competitor
      molecules, which were used as internal standards to compete with matrix effects
      that are evident during DNA extraction and PCR amplification in heterogeneous
      analytical matrixes like food. According to the recently described competitive
      quantitative PCR method published by Holzhauser et al. (2014), we performed
      threshold calibration against milk powder spiked with 10 ppm peanut and soy.
      Matrix-independent quantitative determination of peanut and soy could be
      demonstrated for three different calibrated food matrix standards in a range
      between 1 and 100 ppm. The data presented indicate that both assay concepts are
      powerful analytical tools for the quantitative detection of trace amounts of
      peanut and soy in commercial food products.

PMID- 29202922
TI  - Simultaneous Analysis of Multiple Allergens in Food Products by LC-MS/MS.
AB  - There is currently no cure for food allergies, and sufferers can only rely on the
      correct labeling of foods to avoid allergens. Hence, it is important that
      analytical methods are sensitive and accurate enough to screen for the presence
      of multiple allergens in food products. In this study, we developed an LC-tandem
      MS method that is able to simultaneously screen or quantify the signature tryptic
      peptides of multiple allergen commodities. This method is capable of screening
      and identifying egg white, skim milk, peanut, soy, and tree nuts (almond, Brazil
      nut, cashew, hazelnut, pecan, pine nut, pistachio, and walnut) at a detection
      limit of 10 ppm in incurred bread and cookies. It was further tested for the
      quantitative analysis of whole-egg, whole-milk, peanut butter, and hazelnut
      commodities, which are incurred or spiked into selected food matrixes as defined
      in AOAC INTERNATIONAL Standard Method Performance Requirement (SMPR(r)) 2016.002.
      The method demonstrated excellent sensitivity with a Method quantitative limit of
      3 ppm for whole egg and 10 ppm for the remaining three allergen commodities. It
      also demonstrated good recovery (60-119%) and repeatability (RSDr <20%), with an
      analytical range of 10-1000 ppm for each allergen commodity and was able to meet
      the minimum performance requirements of the SMPR.

PMID- 29202923
TI  - Allergens: An Enhanced Focus.
AB  - Food Allergy Awareness Week was created with the purpose of placing a spotlight
      on the seriousness of food allergies. Recognized in the United States in mid-May
      every year, Food Allergy Awareness Week serves as a reminder of the over 15
      million Americans who suffer from food allergies. The importance of allergies and
      allergen labeling can be seen when looking at U.S. Food and Drug Administration
      recall data: of the 764 recalls in 2016, 305 (representing more than 40%) were
      due to undeclared allergens. However, recalls for undeclared allergens are a
      complex issue with numerous factors. The implementation of prevention-based
      systems with the necessary management components and further error-proofing the
      systems, along with allergen awareness embedded throughout a company's food
      safety culture, can likely help reduce the number of recalls for undeclared
      allergens. As a resource to manufacturers, the Grocery Manufacturers Association
      and the Food Allergy Research and Resource Program have developed several
      resources to assist with developing robust allergen management programs. By
      reducing the number of recalls for undeclared allergens, the food industry will
      likely increase and maintain consumer confidence and trust of the food-allergic
      community. This enhanced consumer confidence and trust could eventually open the
      door for further collaboration with the food-allergic community and, potentially,
      advance allergen-related policies.

PMID- 29202924
TI  - Mental health consultations in the perinatal period: a cost-analysis of Medicare
      services provided to women during a period of intense mental health reform in
      Australia.
AB  - Objective To quantify total provider fees, benefits paid by the Australian
      Government and out-of-pocket patients' costs of mental health Medicare Benefits
      Schedule (MBS) consultations provided to women in the perinatal period (pregnancy
      to end of the first postnatal year).Method A retrospective study of MBS
      utilisation and costs (in 2011-12 A$) for women giving birth between 2006 and
      2010 by state, provider-type, and geographic remoteness was undertaken.Results
      The cost of mental health consultations during the perinatal period was
      A$17.5million for women giving birth in 2007, rising to A$29million in 2010.
      Almost 9% of women giving birth in 2007 had a mental health consultation compared
      with more than 14% in 2010. An increase in women accessing consultations, along
      with an increase in the average number of consultations received, were the main
      drivers of the increased cost, with costs per service remaining stable. There was
      a shift to non-specialist care and bulk billing rates increased from 44% to 52%
      over the study period. In 2010, the average total cost (provider fees) per woman
      accessing mental health consultations during the perinatal period was A$689, and
      the average cost per service was A$133. Compared with women residing in regional
      and remote areas, women residing in major cities where more likely to access
      consultations, and these were more likely to be with a psychiatrist rather than
      an allied health professional or general practitioner.Conclusion Increased access
      to mental health consultations has coincided with the introduction of recent
      mental health initiatives, however disparities exist based on geographic
      location. This detailed cost analysis identifies inequities of access to
      perinatal mental health services in regional and remote areas and provides
      important data for economic and policy analysis of future mental health
      initiatives.What is known about the topic? The mental healthcare landscape in
      Australia has changed significantly over the last decade, with the introduction
      of numerous policies aimed at prevention, screening and improving access to
      treatment. Several of these policies have been aimed at perinatal depression,
      which affects 15% of women giving birth.What does this paper add? This is the
      first population-based, cost analysis of mental health consultations during the
      perinatal period (pregnancy to end of the first postnatal year) in Australia.
      Almost 9% of women giving birth in 2007 had a mental health consultation funded
      though the MBS, compared with more than 14% in 2010. Over the same period there
      was a shift from psychiatric consultations to allied health and primary care
      consultations. In 2010, the total cost (provider fee) of these consultations was
      A$29million, equating to an average cost per woman of A$689 and A$133 per
      service. Despite the changing policy environment, significant disparities exist
      in access to care according to geographic remoteness.What are the implications
      for practitioners? Recent policy initiatives have resulted in increasing access
      to mental health consultations for women around the time of childbirth. However,
      policies are needed that target women outside of major cities. Furthermore,
      evidence is needed on whether the increase in access has resulted in improved
      mental health outcomes for women at this vulnerable time. The cost data provided
      by this study are unique and will inform future mental health policy development
      and health economic evaluations.

PMID- 29202927
TI  - Looking inside the cell.
AB  - Advances in imaging techniques have shed new light on the structure of vesicles
      formed by COPI protein complexes.

PMID- 29202925
TI  - The Investigation of Suspected Fracture-a Comparison of Ultrasound With
      Conventional Imaging.
AB  - BACKGROUND: Ultrasound imaging can be used to diagnose fractures in patients with
      acute trauma. Its main advantages over conventional imaging are the absence of
      radiation exposure and its greater availability. METHODS: A systematic search in
      electronic databases (Medline, Embase, Cochrane CENTRAL) was supplemented by a
      manual search on the Internet and in the reference lists of pertinent
      publications. The QUADAS-2 instrument was used to assess the quality of the
      individual studies retrieved. In the metaanalysis, the sensitivity and
      specificity of the individual studies were pooled. RESULTS: The available
      information on the diagnostic accuracy of ultrasound in the detection of
      fractures compared with that of conventional imaging (x-ray, CT, MRI) in patients
      with acute non-life-threatening trauma is summarized. The database search yielded
      2153 hits, among which there were 48 studies that were suitable for inclusion in
      this review. The pooled sensitivity and specificity were 0.91 (95% confidence
      interval [0.90; 0.92]) and 0.94 [0.93; 0.95], although the analyzed studies were
      markedly heterogeneous (I2: sensitivity 74%, specificity 81%). The sensitivity of
      ultrasound was higher for the detection of fractures of the humerus, the forearm,
      the ankle, and the long bones in general, as well as fractures in children, and
      lower for fractures of the short bones of the hands and feet, and in adults.
      CONCLUSION: Strong evidence supports the use of ultrasound imaging for certain
      indications in the detection of fractures.

PMID- 29202926
TI  - Impingement Syndrome of the Shoulder.
AB  - BACKGROUND: Shoulder pain is the third most common musculoskeletal complaint in
      orthopedic practice. It is usually due to a defect of the rotator cuff and/or an
      impingement syndrome. METHODS: This review is based on pertinent literature
      retrieved by a selective search of the Medline database. RESULTS: Patients with
      shoulder impingement syndrome suffer from painful entrapment of soft tissue
      whenever they elevate the arm. The pathological mechanism is a structural
      narrowing in the subacromial space. A multiplicity of potential etiologies makes
      the diagnosis more difficult; it is established by the history and physical
      examination and can be confirmed with x-ray, ultra - sonography, and magnetic
      resonance imaging. The initial treatment is conservative, e.g., with nonsteroidal
      antiinflammatory drugs, infiltrations, and patient exercises. Conservative
      treatment yields satisfactory results within 2 years in 60% of cases. If symptoms
      persist, decompressive surgery is performed as long as the continuity of the
      rotator cuff is preserved and there is a pathological abnormality of the bursa.
      The correct etiologic diagnosis and choice of treatment are essential for a good
      outcome. The formal evidence level regarding the best treatment strategy is low,
      and it has not yet been determined whether surgical or conservative treatment is
      better. CONCLUSION: Randomized controlled therapeutic trials are needed so that a
      standardized treatment regimen can be established.

PMID- 29202930
TI  - A Difference That Makes a Difference.

PMID- 29202928
TI  - Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar
      invagination.
AB  - Several human diseases are associated with a lack of caveolae. Yet, the functions
      of caveolae and the molecular mechanisms critical for shaping them still are
      debated. We show that muscle cells of syndapin III KO mice show severe reductions
      of caveolae reminiscent of human caveolinopathies. Yet, different from other
      mouse models, the levels of the plasma membrane-associated caveolar coat proteins
      caveolin3 and cavin1 were both not reduced upon syndapin III KO. This allowed for
      dissecting bona fide caveolar functions from those supported by mere caveolin
      presence and also demonstrated that neither caveolin3 nor caveolin3 and cavin1
      are sufficient to form caveolae. The membrane-shaping protein syndapin III is
      crucial for caveolar invagination and KO rendered the cells sensitive to membrane
      tensions. Consistent with this physiological role of caveolae in counterpoising
      membrane tensions, syndapin III KO skeletal muscles showed pathological
      parameters upon physical exercise that are also found in CAVEOLIN3 mutation
      associated muscle diseases.

PMID- 29202929
TI  - Live imaging of heart tube development in mouse reveals alternating phases of
      cardiac differentiation and morphogenesis.
AB  - During vertebrate heart development, two progenitor populations, first and second
      heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of
      the heart tube (HT), with the FHF contributing the left ventricle and part of the
      atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac
      differentiation and morphogenesis by tracking individual cells in live analysis
      of mouse embryos. We report that during an initial phase, FHF precursors
      differentiate rapidly to form a cardiac crescent, while limited morphogenesis
      takes place. In a second phase, no differentiation occurs while extensive
      morphogenesis, including splanchnic mesoderm sliding over the endoderm, results
      in HT formation. In a third phase, cardiac precursor differentiation resumes and
      contributes to SHF-derived regions and the dorsal closure of the HT. These
      results reveal tissue-level coordination between morphogenesis and
      differentiation during HT formation and provide a new framework to understand
      heart development.

PMID- 29202931
TI  - Less-Intensive Screening Does Not Reduce the Frequency of Overdiagnosis.

PMID- 29202932
TI  - Breast Cancer Screening Frequency and Overdiagnosis.

PMID- 29202933
TI  - The Search for the Thyroid Nodule of Interest.

PMID- 29202934
TI  - Authors' Reply.

PMID- 29202935
TI  - Author's Reply-Re: Burnout: A Clinical and Sociological Reflection.

PMID- 29202936
TI  - Refining the Wild Wild West of Point-of-Care Ultrasound at an Academic Community
      Hospital.

PMID- 29202937
TI  - Youth Sport-Related Concussions: Perceived and Measured Baseline Knowledge of
      Concussions Among Community Coaches, Athletes, and Parents.
AB  - OBJECTIVE: To assess concussion knowledge of athletes, coaches, and
      parents/guardians in a community setting and to understand trends/gaps in
      knowledge among subgroups to tailor efforts toward creating educational
      interventions. PARTICIPANTS AND METHODS: This prospective cross-sectional study
      involved 262 individuals (142 [55%] female): 115 athletes participating in
      noncontact and contact sports (ages 13-19 years), 15 coaches, and 132 parents.
      Recruitment occurred from August 30, 2015, through August 30, 2016, at 3 local
      high schools. Participants completed a questionnaire developed by the
      investigators to assess concussion experience and basic knowledge. RESULTS:
      Females, health care employees, and parents showed stronger concern for potential
      long-term sequelae of concussion, whereas athletes were most concerned about not
      being able to return to sport. Those with higher perceived concussion knowledge
      were slightly older (median age, 42.5 vs 33 years), more educated (college or
      higher: 42 [70%] vs 100 [50%]), and more likely to be health care workers (22
      [37.9%] vs 34 [17.7%]) and scored higher on knowledge questions (average correct:
      75.5% vs 60%). Most participants could identify potential concussion sequelae,
      but only 86 (34.3%) identified a concussion as a brain injury. Of the subgroups,
      coaches scored highest on knowledge questions. Those with a concussion history
      tended to consider themselves more knowledgeable but were also less concerned
      about sequelae. Overall, those with a concussion history scored slightly higher
      on knowledge questions (average correct: 69.8% vs 61.9%). Participants involved
      in contact sports were more likely to have had a concussion vs those in
      noncontact sports (57 [26%] vs 4 [10.3%]). CONCLUSION: Significant differences in
      perceived and actual concussion knowledge across different subgroups of study
      participants involved in high school sports were identified.

PMID- 29202938
TI  - Prevalence of Monoclonal Gammopathy in Wild-Type Transthyretin Amyloidosis.
AB  - OBJECTIVE: To evaluate the prevalence of monoclonal gammopathy (MG) in patients
      with wild-type transthyretin amyloidosis (ATTRwt) (formerly known as senile
      amyloidosis). PATIENTS AND METHODS: We retrospectively analyzed the serum protein
      electrophoresis and serum immunofixation results, free light chain (FLC) levels,
      and renal function of 113 consecutive patients with ATTRwt seen at the Brigham
      and Women's Hospital's Cardiac Amyloidosis Program between February 21, 2006, and
      November 9, 2016. Monoclonal gammopathy was defined as a monoclonal protein
      present in the serum. Light chain MG was defined as an abnormal serum FLC
      kappa/lambda ratio with an elevated FLC level in the absence of a monoclonal
      protein. In patients with renal dysfunction, the renal FLC reference range was
      used. RESULTS: The mean age of the population was 75 years, 3 of the 113 patients
      (3%) were female, and 110 (97%) were white. Monoclonal gammopathy was present in
      26 patients (23%), 24 of whom had monoclonal protein present and 2 others who met
      criteria for light chain MG. Most clones (12 of 20 [60%]) were lambda restricted.
      Another 7 patients had an abnormal FLC kappa/lambda ratio in the setting of renal
      dysfunction. CONCLUSION: In this study, MG was present in 23% of patients with
      ATTRwt. The finding of MG or an abnormal FLC kappa/lambda ratio in an elderly man
      may cause diagnostic confusion during subtyping of amyloidosis. A high degree of
      clinical suspicion for ATTRwt and precise tissue typing using mass spectrometry
      may overcome such diagnostic challenges.

PMID- 29202939
TI  - Risk Factors for Herpes Zoster: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: To systematically review studies examining risk factors for herpes
      zoster (HZ). METHODS: We performed a literature search using PubMed, EMBASE, and
      Web of Science for articles published from January 1, 2003, to February 1, 2017.
      A random-effects model was used to summarize the risk ratio (RR) or odds ratio
      (OR) and 95% CI. RESULTS: Of the 3450 studies screened, we included 84 studies in
      the systematic review and conducted meta-analysis in 62 studies. Women were at
      increased risk of HZ compared with men (pooled adjusted RR, 1.31; 95% CI, 1.27
      1.34). Black individuals had almost half the risk of HZ as white individuals
      (pooled RR, 0.54; 95% CI, 0.47-0.63). Family history was found to be a risk
      factor for HZ (pooled OR, 3.59; 95% CI, 2.39-5.40). Autoimmune diseases,
      including rheumatoid arthritis (pooled RR, 1.67; 95% CI, 1.41-1.98) and systemic
      lupus erythematosus (pooled RR, 2.10; 95% CI, 1.40-3.15), were associated with an
      elevated risk of HZ. Other comorbidities were associated with an increased risk
      of HZ, with the pooled RRs ranging from 1.25 (95% CI, 1.13-1.39) for asthma to
      1.30 (95% CI, 1.17-1.45) for diabetes mellitus and 1.31 (95% CI, 1.22-1.41) for
      chronic obstructive pulmonary disease. CONCLUSION: Our review revealed that
      female sex, race/ethnicity, family history, and comorbidities are risk factors
      for HZ. Efforts are needed to increase the uptake of zoster vaccination.

PMID- 29202940
TI  - Genitourinary Syndrome of Menopause: Management Strategies for the Clinician.
AB  - Genitourinary syndrome of menopause (GSM), previously known as atrophic vaginitis
      or vulvovaginal atrophy, affects more than half of postmenopausal women. Caused
      by low estrogen levels after menopause, it results in bothersome symptoms,
      including vaginal dryness, itching, dyspareunia, urinary urgency and increased
      frequency, and urinary tract infections. Even though women with GSM can have
      sexual dysfunction that interferes with partner relationships, women are often
      embarrassed to seek treatment, and health care professionals do not always
      actively screen for GSM. As a result, GSM remains underdiagnosed and
      undertreated. Several effective treatments exist, but low-dose vaginal estrogen
      therapy is the criterion standard. It is effective and safe for most patients,
      but caution is suggested for survivors of hormone-sensitive cancers. Newer
      treatment options include selective estrogen receptor modulators, vaginal
      dehydroepiandrosterone, and laser therapy. Nonprescription treatments include
      vaginal lubricants, moisturizers, and dilators. Pelvic floor physical therapy may
      be indicated for some women with concomitant pelvic floor muscle dysfunction. Sex
      therapy may be helpful for women with sexual dysfunction. This concise review
      presents a practical approach to the evaluation and management of GSM for the
      primary care physician.

PMID- 29202941
TI  - 24-Year-Old Man With Acute Chest Pain.

PMID- 29202944
TI  - Correction.

PMID- 29202942
TI  - Microbiome at the Frontier of Personalized Medicine.
AB  - The genomic revolution promises to transform our approach to treat patients by
      individualizing treatments, reducing adverse events, and decreasing health care
      costs. The early advances using this have been realized primarily by optimizing
      preventive and therapeutic approaches in cancer using human genome sequencing.
      The ability to characterize the microbiome, which includes all the microbes that
      reside within and upon us and all their genetic elements, using next-generation
      sequencing allows us to now incorporate this important contributor to human
      disease into developing new preventive and therapeutic strategies. In this review
      we highlight the importance of the microbiome in all aspects of human disease,
      including pathogenesis, phenotype, prognosis, and response to treatment, as well
      as their role as diagnostic and therapeutic biomarkers. We provide a role for
      next-generation sequencing in both precise microbial identification of infectious
      diseases and characterization of microbial communities and their function. Taken
      together, the microbiome is emerging as an integral part of precision medicine
      approach as it not only contributes to interindividual variability in all aspects
      of a disease but also represents a potentially modifiable factor that is amenable
      to targeting by therapeutics.

PMID- 29202943
TI  - U-Shaped Association Between Body Mass Index and Psychological Distress in a
      Population Sample of 114,218 British Adults.

PMID- 29202945
TI  - Diffuse Venous Thrombosis.

PMID- 29202946
TI  - Ductal Carcinoma in Situ of the Breast.

PMID- 29202947
TI  - 59-Year-Old Woman With Fatigue, Dyspnea, and Lower Extremity Edema.

PMID- 29202949
TI  - Looking Back, Looking Ahead, Revisited.

PMID- 29202948
TI  - Queen Anne's Lace, Gooseneck Loosestrife, Untitled (Poppy Maidenhair Fern),
      Blushing Deathcap, Untitled (Trillium), and Untitled (Trillium, Pear Blossom,
      Salamander) by Victor Schrager.
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- 29202950
TI  - Strings of the Heart.

PMID- 29202951
TI  - Sometimes You Have to Tilt Your Head and Strain to Take a Picture of the Truth.

PMID- 29202953
TI  - ASE Foundation Needs Your Support!

PMID- 29202954
TI  - Looking Back and Forward.

PMID- 29202952
TI  - Factors Influencing Pediatric Outpatient Transthoracic Echocardiography
      Utilization Before Appropriate Use Criteria Release: A Multicenter Study.
AB  - BACKGROUND: Although pediatric appropriate use criteria (AUC) for outpatient
      transthoracic echocardiography (TTE) are available, little is known about TTE
      utilization patterns before their release. The aims of this study were to
      determine the relation between AUC and TTE utilization and to identify patient
      and physician factors associated with discordance between the AUC and clinical
      practice. METHODS: A retrospective review of 3,000 initial outpatient pediatric
      cardiology encounters at six centers was performed. Investigator-determined
      indications were classified using AUC definitions. Concordance between AUC and
      TTE utilization was determined. Multivariate analysis was performed to identify
      patient and physician factors associated with TTE's being performed for rarely
      appropriate and TTE's not being performed for appropriate indications. RESULTS:
      Concordance between AUC and TTE utilization was 88%. TTE was performed for rarely
      appropriate indications in 9% and was associated with patient age < 3 months,
      indications of murmur, noninvasive imaging physician subspecialty, and physician
      volume. No TTE was ordered for appropriate indications in 3% and was associated
      with indications including prior test result (primarily abnormal
      electrocardiographic findings), older patients, and physician subspecialty other
      than generalist or imaging. There was high variability in TTE utilization among
      centers. CONCLUSIONS: There was a reasonable degree of concordance between AUC
      and clinical practice before AUC publication. Several patient and physician
      factors were associated with discordance with the AUC. These findings should be
      considered in efforts to disseminate the AUC and in the development of future
      iterations. The causes for variation among centers deserve further exploration.

PMID- 29202955
TI  - Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis
      and pelvic pain or infertility-related gynecologic disorders.
AB  - OBJECTIVE: To investigate the usefulness of soluble galectin-9 (Gal-9) in the
      noninvasive laboratory diagnosis of endometriosis and various gynecologic
      disorders. DESIGN: Prospective case-control study. SETTING: University medical
      centers. PATIENT(S): A total of 135 women of reproductive age were involved in
      the study, 77 endometriosis patients, 28 gynecologic controls, and 30 healthy
      women. INTERVENTION(S): Diagnostic laparoscopy and collection of tissue biopsies,
      peritoneal cells, and native peripheral blood from different case groups of
      gynecology patients and healthy women. MAIN OUTCOME MEASURE(S): The expression of
      mRNA and serum concentration of Gal-9. RESULT(S): Semiquantitative reverse
      transcription-polymerase chain reaction analysis and serum soluble Gal-9 ELISA
      were performed on three different cohorts of patients: those with endometriosis,
      those with benign gynecologic disorders, and healthy controls. Differences in the
      Gal-9 concentrations between the investigated groups and the stability of Gal-9
      in the serum and diagnostic characteristics of Gal-9 ELISA were determined by
      statistical evaluation and receiver operating characteristic (ROC) curve
      analysis. Significantly elevated Gal-9 levels were found in both minimal-mild (I
      II) and moderate-severe (III-IV) stages of endometriosis in comparison with
      healthy controls. At a cutoff of 132 pg/mL, ROC analysis revealed an excellent
      diagnostic value of Gal-9 ELISA in endometriosis (area under the curve = 0.973)
      with a sensitivity of 94% and specificity of 93.75%, indicating better diagnostic
      potential than that of other endometriosis biomarkers. Furthermore, various
      pelvic pain or infertility-associated benign gynecologic conditions were also
      associated with increased serum Gal-9 levels. CONCLUSION(S): Our results suggest
      that Gal-9 could be a promising noninvasive biomarker of endometriosis and a
      predictor of various infertility or pelvic pain-related gynecologic disorders.

PMID- 29202957
TI  - Parental influences on sperm banking attempts among adolescent males newly
      diagnosed with cancer.
AB  - OBJECTIVE: To investigate the influence of parental sociodemographic,
      communication, and psychological factors on sperm collection attempts among at
      risk adolescent males newly diagnosed with cancer. DESIGN: Prospective, single
      group, observational study design. SETTING: Pediatric oncology centers.
      PATIENT(S): Parents (N = 144) of 122 newly diagnosed adolescent males at
      increased risk for infertility secondary to cancer therapy. INTERVENTION(S):
      Survey-based assessment of parent factors associated with adolescent collection
      attempts. MAIN OUTCOME MEASURE(S): Attempt of manual collection of sperm.
      RESULT(S): Parental recommendation to bank sperm (odds ratio [OR] 3.72; 95%
      confidence interval [CI] 1.18-11.76) and perceived self-efficacy to facilitate
      banking (OR 1.20; 95% CI 1.02-1.41) were associated with an increased likelihood
      of making a collection attempt. CONCLUSION(S): Parental recommendation to bank is
      a critical influence for sperm banking among adolescent males newly diagnosed
      with cancer. These findings highlight the importance of effective communication
      between parents, patients, and health-care teams when discussing preservation
      options. Parent perceptions of their ability to facilitate sperm banking at the
      time of diagnosis should also be targeted in future interventions. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT01152268.

PMID- 29202956
TI  - Admixture mapping of uterine fibroid size and number in African American women.
AB  - OBJECTIVE: To evaluate the relationship between genetic ancestry and uterine
      fibroid characteristics. DESIGN: Cross-sectional study. SETTING: Not applicable.
      PATIENT(S): A total of 609 African American participants with image- or surgery
      confirmed fibroids in a biorepository at Vanderbilt University electronic health
      record biorepository and the Coronary Artery Risk Development in Young Adults
      studies were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome
      measures include fibroid number (single vs. multiple), volume of largest fibroid,
      and largest fibroid dimension of all fibroid measurements. RESULT(S): Global
      ancestry meta-analyses revealed a significant inverse association between
      percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78;
      95% confidence interval 0.66, 0.93; P=6.05 * 10-3). Local ancestry meta-analyses
      revealed five suggestive (P<4.80 * 10-3) admixture mapping peaks in 2q14.3
      2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of
      fibroids and one suggestive admixture mapping peak (P<1.97 * 10-3) in 10q24.1
      10q24.32 for volume of largest fibroid. Single variant association meta-analyses
      of the strongest associated region from admixture mapping of fibroid number
      (10q21.1) revealed a strong association at single nucleotide polymorphism variant
      rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 * 10-6)
      that was significant after correction for multiple testing. CONCLUSION(S):
      Increasing African ancestry is associated with multiple fibroids but not with
      fibroid size. Local ancestry analyses identified several novel genomic regions
      not previously associated with fibroid number and increasing volume. Future
      studies are needed to explore the genetic impact that ancestry plays into the
      development of fibroid characteristics.

PMID- 29202958
TI  - Transcriptome-wide association study revealed two novel genes associated with
      nonobstructive azoospermia in a Chinese population.
AB  - OBJECTIVE: To investigate the associations between genetically cis-regulated gene
      expression levels and nonobstructive azoospermia (NOA) susceptibility. DESIGN:
      Transcriptome-wide association study (TWAS). SETTING: Medical university.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The cis-hg2 values for each gene
      were estimated with GCTA software. The effect sizes of cis-single-nucleotide
      polymorphisms (SNPs) on gene expression were measured using GEMMA software. Gene
      expression levels were entered into our existing NOA GWAS cohort using GEMMA
      software. The TWAS P-values were calculated using logistic regression models.
      RESULT(S): Expression levels of 1,296 cis-heritable genes were entered into our
      existing NOA GWAS data. The TWAS results identified two novel genes as
      statistically significantly associated with NOA susceptibility: PILRA and ZNF676.
      In addition, 6p21.32, previously reported in NOA GWAS, was further validated to
      be a susceptible region to NOA risk. CONCLUSION(S): Analysis with TWAS provides
      fruitful targets for follow-up functional studies.

PMID- 29202959
TI  - Antimullerian hormone levels and antral follicle counts are not reduced compared
      with community controls in patients with rigorously defined unexplained
      infertility.
AB  - OBJECTIVE: To test the hypothesis that women with unexplained infertility
      demonstrate evidence of diminished ovarian reserve when compared with a
      population of community controls. DESIGN: Cross-sectional study. SETTING:
      Multicenter university-based clinical practices. PATIENT(S): Study participants
      included 277 healthy, normo-ovulatory female partners with rigorously defined
      unexplained infertility randomly selected from a multicenter trial (Assessment of
      Multiple Intrauterine Gestations from Ovarian Stimulation). Controls included 226
      healthy, normo-ovulatory women not seeking treatment for fertility from a
      community-based cohort (Ovarian Aging study). INTERVENTION(S): Serum
      antimullerian hormone (AMH) assay at a central laboratory, FSH, fasting serum
      metabolic testing, transvaginal ultrasonography for antral follicle counts
      (AFCs), anthropometric measurements. MAIN OUTCOME MEASURE(S): Average AMH, AFC,
      and AMH/AFC were compared between infertile and control women by age. Analyses of
      covariance compared these outcomes while controlling for confounders, including
      age, race, body mass index, smoking history, and study site. RESULT(S): In our
      models, AMH, AFC, and AMH/AFC ovarian reserve indices did not differ between
      infertile women and community-based controls, after controlling for age, race,
      body mass index, smoking history, and study site. CONCLUSION(S): Currently
      utilized predictors of ovarian reserve do not discriminate women with rigorously
      defined unexplained infertility from healthy community-based women of similar
      demographic characteristics. Contrary to our hypothesis, among women with FSH in
      the normal range (<=12 IU/L), women with unexplained infertility did not show
      evidence of decreased ovarian reserve as measured by AMH and AFC. Ovarian reserve
      markers in isolation may not serve as predictors of future fertility.

PMID- 29202961
TI  - Erratum.

PMID- 29202960
TI  - Polycystic ovary syndrome is a risk factor for diabetes and prediabetes in middle
      aged but not elderly women: a long-term population-based follow-up study.
AB  - OBJECTIVE: To study the incidence rate and hazard ratios of diabetes and
      prediabetes between women with PCOS and healthy subjects. DESIGN: Prospective
      population-based study. SETTING: Not applicable. PATIENT(S): Women with PCOS (n =
      178) and eumenorrheic, nonhirsute, healthy women as controls (n = 1,524), all
      followed for a median time of 12.9 years. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Incidence rate and hazard ratios of diabetes and prediabetes between
      women with PCOS and healthy controls. RESULT(S): We analyzed the participants on
      two pathways. First, for detecting new diabetes mellitus (DM) events, we selected
      participants who were free of DM at baseline (n = 39). Second, for detecting new
      pre-DM events, we selected participants who were free of pre-DM and DM at
      baseline (n = 222) from the baseline population. The rest of the population were
      included for final analysis to calculate the incidence rates and hazard ratio of
      diabetes and prediabetes events. The incidence rates of diabetes were 12.9 and
      4.9 per 1,000 person-years for PCOS and controls, respectively. This incidence
      rate in women younger than 40 with and without PCOS was 13.4 and 4.2,
      respectively. The adjusted hazard ratio (HR) for women <=40 was 4.9 (95%
      confidence interval [CI], 2.5-9.3). There were no statistically significant
      differences between the two groups studied after age 40. The incidence rates of
      prediabetes were 29.7 and 25.9 per 1,000 person-years for PCOS and healthy women,
      respectively. The incidence rate in women younger than 40 with and without PCOS
      was 30.3 and 23.9, respectively. The adjusted HR for women <=40 years, 1.7 (95%
      CI, 1.1-2.6), disappeared after age 40. CONCLUSION(S): These data suggest that
      routine screening for diabetes in prevention strategies does not need to be
      emphasized for PCOS patients at late reproductive ages if they have not been
      affected by glucose intolerance up to that point.

PMID- 29202962
TI  - Introduction: From pathogenesis to therapy, deep endometriosis remains a source
      of controversy.
AB  - Deep endometriosis remains a source of controversy. A number of theories may
      explain its pathogenesis and many arguments support the hypothesis that genetic
      or epigenetic changes are a prerequisite for development of lesions into deep
      endometriosis. Deep endometriosis is frequently responsible for pelvic pain,
      dysmenorrhea, and/or deep dyspareunia, but can also cause obstetrical
      complications. Diagnosis may be improved by high-quality imaging. Therapeutic
      approaches are a source of contention as well. In this issue's Views and Reviews,
      medical and surgical strategies are discussed, and it is emphasized that
      treatment should be designed according to a patient's symptoms and individual
      needs. It is also vital that referral centers have the knowledge and experience
      to treat deep endometriosis medically and/or surgically. The debate must continue
      because emerging trends in therapy need to be followed and investigated for
      optimal management.

PMID- 29202963
TI  - Diagnosis of deep endometriosis: clinical examination, ultrasonography, magnetic
      resonance imaging, and other techniques.
AB  - The aim of the present review was to evaluate the contribution of clinical
      examination and imaging techniques, mainly transvaginal sonography and magnetic
      resonance imaging (MRI) to diagnose deep infiltrating (DE) locations using prisma
      statement recommendations. Clinical examination has a relative low sensitivity
      and specificity to diagnose DE. Independently of DE locations, for all
      transvaginal sonography techniques a pooled sensitivity and specificity of 79%
      and 94% are observed approaching criteria for a triage test. Whatever the
      protocol and MRI devices, the pooled sensitivity and specificity for pelvic
      endometriosis diagnosis were 94% and 77%, respectively. For rectosigmoid
      endometriosis, pooled sensitivity and specificity of MRI were 92% and 96%,
      respectively fulfilling criteria of replacement test. In conclusion, advances in
      imaging techniques offer high sensitivity and specificity to diagnose DE with at
      least triage value and for rectosigmoid endometriosis replacement value imposing
      a revision of the concept of laparoscopy as the gold standard.

PMID- 29202964
TI  - Obstetrical complications of endometriosis, particularly deep endometriosis.
AB  - Over the past few years, a new topic in the field of endometriosis has emerged:
      the potential impact of the disease on pregnancy outcomes. This review aims to
      summarize in detail the available evidence on the relationship between
      endometriosis, particularly deep endometriosis (DE), and obstetrical outcomes.
      Acute complications of DE, such as spontaneous hemoperitoneum, bowel perforation,
      and uterine rupture, may occur during pregnancy. Although these events represent
      life-threatening conditions, they are rare and unpredictable. Therefore, the
      current literature does not support any kind of prophylactic surgery before
      pregnancy to prevent such complications. Results on the impact of DE on
      obstetrical outcomes are debatable and characterized by several limitations,
      including small sample size, lack of adjustment for confounders, lack of adequate
      control subjects, and other methodologic flaws. For these reasons, it is not
      possible to draw conclusions on this topic. The strongest evidence shows that DE
      is associated with higher rates of placenta previa; for other obstetrical
      outcomes, such as miscarriage, intrauterine growth restriction, preterm birth and
      hypertensive disorders, results are controversial. Although it is unlikely that
      surgery of DE may modify the impact of the disease on the course of pregnancy, no
      study has yet investigated this issue.

PMID- 29202965
TI  - Role of medical therapy in the management of deep rectovaginal endometriosis.
AB  - Defining whether medical therapy is effective in women with deep rectovaginal
      endometriosis and in which circumstances it can be considered an alternative to
      surgery is important for patients and physicians. Numerous observational and some
      randomized controlled studies demonstrated that different hormonal drugs improved
      pain and other symptoms in approximately two-thirds of women with deep
      rectovaginal endometriosis. Because major differences in the effect size of
      various compounds were not observed, much importance should be given to safety,
      tolerability, and cost of medications when counseling patients. Progestins seem
      to offer the best therapeutic balance when long-term treatments are planned.
      Women should be informed that hormonal drugs control but do not cure
      endometriosis and that, to avoid surgery, they should be used for years. Medical
      therapy is not an alternative to surgery in women with hydronephrosis, severe
      subocclusive bowel symptoms, and in those wishing a natural conception. A
      progestin should systematically be chosen as a comparator in future randomized
      trials on novel medications for deep endometriosis. In the meantime, the use of
      existing drugs should be optimized, and medical and surgical treatments could be
      viewed as subsequent stages of a stepwise approach. In general, there is no
      absolute "best" choice, and women must be thoroughly informed of potential
      benefits, potential harms, and costs of different therapeutic options and allowed
      to choose what they deem is better for them.

PMID- 29202966
TI  - Choosing the right surgical technique for deep endometriosis: shaving, disc
      excision, or bowel resection?
AB  - Deep endometriosis (DE) remains the most difficult endometriotic entity to treat.
      Medical treatment for DE can reduce symptoms but does not cure the disease, and
      surgical removal of the lesion is required when lesions are symptomatic,
      impairing bowel, urinary, sexual, and reproductive functions. Although several
      surgical techniques such as laparoscopic bowel resection, disc excision, and
      rectal shaving have been described, there is no consensus regarding the choice of
      technique or the timing of surgery. Our review of publications reporting results
      and complications of surgery for rectovaginal DE reveals a relatively higher
      complication rate after bowel resection compared with shaving and disc excision,
      especially for rectovaginal fistulas, anastomotic leakage, delayed hemorrhage,
      and long-term bladder catheterization. Data show that shaving is feasible even in
      advanced disease. The risk of immediate complications after shaving and disc
      excision is probably lower than after colorectal resection, allowing for better
      functional outcomes. The presumed higher risk of recurrence related to shaving
      has not been demonstrated. For these reasons, surgeons should consider rectal
      shaving as a first-line surgical treatment of rectovaginal DE, regardless of
      nodule size or association with other digestive localizations. When the result of
      rectal shaving is unsatisfactory (rare cases), disc excision may be performed
      either exclusively by laparoscopy or by using transanal staplers. Segmental
      resection may ultimately be reserved for advanced lesions responsible for major
      stenosis or for several cases of multiple nodules infiltrating the rectosigmoid
      junction or sigmoid colon.

PMID- 29202967
TI  - Does cumulative live birth plateau beyond a certain ovarian response?

PMID- 29202968
TI  - Child-rearing ability and the provision of fertility services: an Ethics
      Committee opinion.
AB  - Fertility programs may withhold services from prospective patients on the basis
      of well-grounded reasons that those patients will be unable to provide minimally
      adequate or safe care for offspring. This document was reviewed and updated; this
      version replaces the previous version of this document, last published July 2013
      (Fertil Steril 2013;100:50-53).

PMID- 29202969
TI  - Markers of ovarian reserve: is it possible to estimate an ovarian age?

PMID- 29202970
TI  - Male factors affect success of assisted reproductive technology.

PMID- 29202971
TI  - Unlocking the cause of increased adverse singleton pregnancy outcomes: the role
      of the assisted reproductive technology derived embryo.

PMID- 29202972
TI  - Jack LaLanne got it right.

PMID- 29202973
TI  - Does the risk of diabetes and heart disease in women with polycystic ovary
      syndrome lessen with age?

PMID- 29202974
TI  - Embryo aneuploidy is not impacted by selective serotonin reuptake inhibitor
      exposure.
AB  - OBJECTIVE: To study whether maternal exposure to selective serotonin reuptake
      inhibitors (SSRIs) has any influence on rates of blastocyst aneuploidy and/or in
      vitro fertilization (IVF) cycle outcomes. DESIGN: Retrospective cohort analysis.
      SETTING: Private and academic IVF center. PATIENT(S): Patients who underwent IVF
      with preimplantation genetic treatment with trophectoderm biopsy (n = 4,355
      cycles) and patients who underwent a single-embryo transfer (SET) between January
      2012 and June-2017 (n = 2,132 cycles). INTERVENTION(S): Comprehensive chromosome
      screening and euploid SET. MAIN OUTCOME MEASURE(S): Odds of embryo aneuploidy.
      RESULT(S): Of 19,464 embryos analyzed, 3.9% (n = 743) were exposed to a SSRI, and
      the remaining 96.1% (n = 18,721) were not. The embryo euploid rate was 52.1%, and
      the aneuploid rate was 42.5%; 5.4% of the reports were inconclusive. No
      differences were found in clinical and IVF characteristics among the cohorts.
      After controlling for cofounders, there was no statistically significant
      associations between exposure to SSRIs and the odds of aneuploidy (adjusted odds
      ratio [OR] 0.04; 95% confidence interval [CI], -0.04-0.09). In a subanalysis
      including 2,132 thawed SET cycles, no differences were observed in implantation
      rate (71.3% vs. 70.1%; OR 0.60; 95% CI, 0.60-1.47), clinical pregnancy rate
      (58.2% vs. 59.7%; OR 0.70; 95% CI, 0.70-1.61), loss rate (18.5% vs. 11.49%; OR
      1.54; 95% CI, 0.94-2.54), or multiple pregnancy rate (0.6% vs. 0; OR 0.7; 95% CI,
      0.02-7.32) between cohorts. CONCLUSION(S): Patients exposed to SSRIs in vivo are
      not susceptible to an increased rate of embryo aneuploidy in IVF. The IVF
      outcomes of patients exposed to SSRIs do not differ from those of unexposed
      patients.

PMID- 29202976
TI  - Perinatal outcomes after natural conception versus in vitro fertilization (IVF)
      in gestational surrogates: a model to evaluate IVF treatment versus maternal
      effects.
AB  - OBJECTIVE: To study the perinatal outcomes between singleton live births achieved
      with the use of commissioned versus spontaneously conceived embryos carried by
      the same gestational surrogate. DESIGN: Retrospective cohort study. SETTING:
      Academic in vitro fertilization center. PATIENT(S): Gestational surrogate.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, gestational
      age at birth, birth weight, perinatal complications. RESULT(S): We identified 124
      gestational surrogates who achieved a total of 494 pregnancies. Pregnancy
      outcomes for surrogate and spontaneous pregnancies were significantly different
      (P<.001), with surrogate pregnancies more likely to result in twin pregnancies:
      33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies,
      there were 352 singleton live births: 103 achieved from commissioned embryos and
      249 conceived spontaneously. Surrogate births had lower mean gestational age at
      delivery (38.8 +/- 2.1 vs. 39.7 +/- 1.4), higher rates of preterm birth (10.7%
      vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from
      surrogacy had birth weights that were, on average, 105 g lower. Surrogate births
      had significantly higher obstetrical complications, including gestational
      diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic
      requirement during labor, and cesarean section. CONCLUSION(S): Neonates born from
      commissioned embryos and carried by gestational surrogates have increased adverse
      perinatal outcomes, including preterm birth, low birth weight, hypertension,
      maternal gestational diabetes, and placenta previa, compared with singletons
      conceived spontaneously and carried by the same woman. Our data suggest that
      assisted reproductive procedures may potentially affect embryo quality and that
      its negative impact can not be overcome even with a proven healthy uterine
      environment.

PMID- 29202978
TI  - Evidence based review of literature on detriments to healing of diabetic foot
      ulcers.
AB  - BACKGROUND: Diabetes mellitus places a substantial burden on society worldwide.
      Diabetic foot ulcers are a challenging problem for clinicians. Seven generally
      accepted detriments to healing of diabetic foot ulcers were identified:
      infection, glycaemic control, vascular supply, smoking, nutrition, deformity and
      offloading. The aim of this paper is to present a comprehensive evidence based
      review of the literature available on detriments to healing of diabetic foot
      ulcers. METHOD: A research question was generated for each of the detriments to
      healing and a comprehensive review of the literature was performed using the
      Pubmed database in July 2014. All articles were assessed for relevancy and a
      level of evidence was assigned. An analysis of the total body of literature was
      used to assign a grade of recommendation to each detriment. RESULTS: Grade A
      recommendation was assigned to offloading as there was good evidence supporting
      this intervention. Grade B recommendation was assigned to deformity as there was
      fair evidence consistent with the hypothesis. Infection and vascular supply had
      poor quality evidence supporting the research question and grade C recommendation
      was assigned. Grade I recommendation was assigned to glycaemic control, smoking
      and nutrition as there was insufficient and conflicting evidence available.
      CONCLUSION: Our literature review revealed good evidence for some factors and
      insufficient literature on others. Further studies are needed to provide quality
      evidence regarding detriments to healing of diabetic ulcers.

PMID- 29202975
TI  - Diminished ovarian reserve as measured by means of baseline follicle-stimulating
      hormone and antral follicle count is not associated with pregnancy loss in
      younger in vitro fertilization patients.
AB  - OBJECTIVE: To assess the relationship between diminished ovarian reserve and
      pregnancy outcomes in a large cohort of women achieving pregnancy through in
      vitro fertilization (IVF). We evaluated antral follicle count (AFC) and baseline
      FSH as a measure of ovarian reserve. Secondarily, we assessed whether diminished
      ovarian reserve was associated with aneuploidy among spontaneous abortions.
      DESIGN: Retrospective cohort study. SETTING: Multicenter private practice.
      PATIENT(S): All patients aged 21-44 years undergoing fresh autologous IVF cycles
      during 2009-2013 that resulted in positive serum hCG with recorded baseline FSH
      levels. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live births per early
      pregnancy, biochemical pregnancies, clinical pregnancy losses, and aneuploidy
      rates in products of conception among pregnancy losses. RESULT(S): A total of
      9,489 cycles among 8,214 patients were analyzed. There was no association between
      live birth and ovarian reserve among pregnant IVF patients under the age of 35
      years. Among patients 35 years of age and older, elevated baseline FSH was
      associated with a higher risk of pregnancy loss, which increased with increasing
      age. AFC was not significantly associated with pregnancy loss at any age. No
      associations were found between ovarian reserve measures and aneuploidy in
      products of conception in age-adjusted analyses, although the power to
      effectively evaluate this was limited. CONCLUSION(S): Diminished ovarian reserve
      is not associated with an increase in miscarriage among younger women achieving
      pregnancy through IVF. Elevated FSH is associated with a higher risk of IVF
      pregnancy loss among older patients. We found no evidence to confirm that
      diminished ovarian reserve is associated with increased aneuploidy among
      spontaneous abortions.

PMID- 29202979
TI  - The functional outcome and quality of life after treatment of isolated medial
      malleolar fractures.
AB  - BACKGROUND: The optimal treatment of isolated medial malleolar fractures is
      widely debated. The aim of this study is to analyse the different treatment
      methods. METHODS: The study included 137 patients with an isolated medial
      malleolar fracture treated at our hospital between 2000 and 2010. Functional
      outcome was assessed using Olerud-Molander score and health-related quality-of
      life (HRQoL) was measured with RAND36 item health survey. Patients were sent
      follow-up questionnaires after an average of 9.5 years (4.3-15.2) from the date
      of treatment. RESULTS: The overall improvement in function was equivalent in both
      operative and non-operative treatment groups. However, the outcome scores
      declined in both groups as the primary displacement increased, regardless of the
      treatment method. HRQoL was similar in both groups. CONCLUSIONS: If maximal
      fracture displacement is <=2mm, isolated medial malleolar fractures can be
      treated non-operatively with good outcome, but the operative treatment may also
      be performed without serious complications. The degree of fracture displacement
      is an independent risk factor for inferior functional result, regardless of the
      treatment method. LEVEL OF EVIDENCE: Therapeutic level of evidence: IV,
      retrospective cohort study.

PMID- 29202980
TI  - Computed tomography measurements of the lesser metatarsal heads: Anatomic
      considerations for surgeons performing distal metatarsal osteotomies.
AB  - BACKGROUND: The purpose of the current study was to provide a standardized,
      anatomical description of the lesser metatarsals to assist surgeons when planning
      distal metatarsal surgery and fixation. METHODS: Eighty CT scans were included
      for assessment, based on a priori power analysis. Patient age was a mean 52.7+/
      16.6 years (24-83). Metatarsals two through five were assessed in all patients.
      Three independent observers completed measurements for all metatarsals. Three
      measurements were made on all metatarsals, including a vertical height and
      metatarsal head and neck measurements. Statistical analysis was performed (alpha
      value 0.05). Inter-observer reliability was assessed for all measurements and
      intra-class correlation (ICC) reported. RESULTS: A sequential decrease in
      metatarsal measurements was noted from the second to the fifth metatarsal. A mean
      vertical height measurement of 16.1+/-1.4mm (range, 13.4-19.4) was recorded for
      the second metatarsal, decreasing 13.0+/-1.1mm (range, 10.3-16.1) for fifth.
      There were no significant differences in metatarsal measurements based on gender
      in our study. Similar patient and metatarsal variability was seen head and neck
      measurements. Intraclass correlation coefficients (ICC) for metatarsal
      measurements were greater than 0.9 [95% CI; 0.936-0.991] correlation, denoting an
      'excellent' interobserver reliability. CONCLUSION: This study provides a baseline
      anatomical description of the distal metatarsals. These findings, including the
      variation found between patients and between metatarsal two through five, are
      relevant to surgeons planning and performing distal metatarsal osteotomies.

PMID- 29202981
TI  - Matrix-associated stem cell transplantation (MAST) in chondral defects of the
      ankle is safe and effective - 2-year-followup in 130 patients.
AB  - BACKGROUND: The aim of the study was to assess the 2-year-follow-up of matrix
      associated stem cell transplantation (MAST) in chondral defects of the ankle.
      METHODS: In a prospective consecutive non-controlled clinical follow-up study,
      all patients with chondral defect that were treated with MAST from October 1,
      2011 to July 31, 2013 were analyzed. Size and location of the chondral defects,
      method-associated problems and the Visual Analogue Scale Foot and Ankle (VAS FA)
      before treatment and at follow-up were analyzed. Stem cell-rich blood was
      harvested from the ipsilateral pelvic bone marrow and centrifuged (10min,
      1500rpm). The supernatant was used to impregnate a collagen I/III matrix (Chondro
      Gide). The matrix was fixed into the chondral defect with fibrin glue. RESULTS:
      One hundred and forty-four patients with 150 chondral defects were included in
      the study. The age of the patients was 35 years on average (range, 12-68 years),
      85 (59%) were male. The VAS FA before surgery was 48.5 on average (range, 16.5
      78.8). The defects were located as follows, medial talar shoulder, n=62; lateral
      talar shoulder, n=66 (medial and lateral talar shoulder, n=6), tibia, n=22. The
      defect size was 1.6cm2 on average (range, .6-6cm2). 130 patients (90%) completed
      2-year-follow-up. The VAS FA improved to an average of 87.5 (range, 62.1-100; t
      test (comparison with preoperative scores), p=.01). CONCLUSIONS: MAST led to
      improved and high validated outcome scores. No method related complications were
      registered. Even though a control group is missing, we conclude that MAST is a
      safe and effective method for the treatment of chondral defects of the ankle.

PMID- 29202982
TI  - Comparison of outcomes of osteosynthesis in type II accessory navicular by
      variable fixation methods.
AB  - BACKGROUND: To compare the outcomes of fixation methods for osteosynthesis of a
      type II symptomatic accessory navicular between screw and tension band wiring.
      METHODS: Forty-four patients (mean age, 29.2 years; range, 13-54 years; 21 males
      and 23 females) who had undergone operative treatment after failed conservative
      treatment were chosen for the study between 2007 and 2014. The patients were
      divided into two groups by the method of osteosynthesis: group 1 (screw) and
      group 2 (tension band wiring). Pre and postoperative evaluations were performed,
      using the midfoot scale from the American Orthopaedic Foot and Ankle Society
      (AOFAS), a visual analog scale, time to return to social activities, and plain
      radiography. RESULTS: The AOFAS midfoot and visual analog scale scores of both
      groups were improved at the last postoperative follow-up. The time to return to
      social activities was 12.3 weeks in the screw group and 11.9 weeks in the tension
      band wiring group (p=0.394). A broken screw was observed in one case in the screw
      group and a broken k-wire was detected in two cases in the tension band wiring
      group. Nonunion was observed in two cases in each group. CONCLUSION: The tension
      band wiring technique could be another treatment choice of osteosynthesis for
      fixation of the accessory navicular bone. LEVEL OF EVIDENCE: Level III,
      Retrospective Case Control Study.

PMID- 29202983
TI  - Influence of tibialis posterior muscle activation on foot anatomy under axial
      loading: A biomechanical CT human cadaveric study.
AB  - BACKGROUND: Collapse of the medial longitudinal arch and subluxation of the
      subtalar joint are common occurrences in adult flatfoot deformity. Controversy
      exists about the role of the tibialis posterior (TP) tendon as first and/or
      essential lesion. Subtle changes in the foot configuration can occur under weight
      bearing. PURPOSE: This human cadaveric study is designed to investigate the
      effect that isolated actuation of the TP tendon has on the medial longitudinal
      arch and the hindfoot configuration under simulated weight bearing. METHODS: A
      radiolucent frame was developed to apply axial loading on cadaveric lower legs
      during computer tomography (CT) examinations. Eight pairs of fresh-frozen
      specimens were imaged in neutral position under foot-flat loading (75N) and under
      single-leg stance weight bearing (700N) without and with addition of 150N pulling
      force on the TP tendon. Measurements of subtalar joint subluxation, forefoot arch
      angle and talo-first metatarsal angle were conducted on each set of CT scans.
      RESULTS: Subtalar subluxation, talo-first metatarsal angle and talo-navicular
      coverage angle significantly increased under single-leg stance weight bearing,
      whereas forefoot arch angle significantly decreased. Actuation of the TP tendon
      under weight bearing did not restore the forefoot arch angle or correct subtalar
      subluxation and talo-metatarsal angle. CONCLUSION: Significant effect that weight
      bearing has on the medial longitudinal arch and the subtalar joint configuration
      is demonstrated in an ex-vivo model. In absence of other medial column
      derangement, actuation of the TP tendon alone does not seem to reconstitute the
      integrity of the medial longitudinal arch or correct the hindfoot subluxation
      under weight bearing. CLINICAL RELEVANCE: The findings of this study together
      with the developed model for ex-vivo investigation provide a further insight in
      foot anatomy.

PMID- 29202984
TI  - Screwless scarf osteotomy for hallux valgus: Evaluation of radiologic correction.
AB  - BACKGROUND: The scarf osteotomy is a standard procedure to correct hallux valgus.
      Recent modifications in the technique allow for important translations of the
      bone fragments without the need for screw fixation. We performed the first
      prospective analysis of radiographic parameters after a screwless scarf
      osteotomy. Prospective study of pre- and postoperative standing radiographs of
      the feet let us quantify angle reduction and shortening, lengthening or lowering
      of the first metatarsal. METHODS: 100 patients undergoing a screwless scarf
      osteotomy were evaluated radiographically before and after surgery. The 1-2 IM
      angle, HVA, length of the first metatarsal, protrusion length and height of the
      first metatarsal head were measured. RESULTS: The mean 1-2 IM angle was reduced
      significantly, to a normal range. The mean reduction of the first metatarsal
      length and protrusion length was 0.3 and 0.14cm respectively. The metatarsal head
      was lowered 0.3cm on average. CONCLUSIONS: A minimal mean reduction of the first
      metatarsal length was observed, but it is possible to lengthen the first
      metatarsal if necessary. In 23% of cases, an increase of protrusion length was
      obtained. The screwless scarf osteotomy results in a good correction of the 1-2
      IM angle and HVA. If necessary, plantarisation of the first metatarsal head could
      be obtained. Secondary displacement was seen in 1 patient. LEVEL OF EVIDENCE:
      IIa, prospective controlled trial.

PMID- 29202985
TI  - Surgical resident involvement in foot and ankle surgery.
AB  - BACKGROUND: Surgical resident participation in the operating room is necessary
      for education and progression toward safe and independent practice. However, the
      impact of resident involvement on patient outcomes in foot and ankle surgery is
      unknown. METHODS: The American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP) database (2005-2012) was used to identify common
      foot and ankle procedures (by Current Procedural Taxonomy (CPT) code) performed
      by orthopedic surgeons. Resident participation was determined using the NSQIP
      collected variable 'pgy'; cases missing the pgy variable were excluded.
      Multivariate regression models were constructed to determine an association
      between resident involvement and 30-day morbidity (total, medical, and surgical
      complications) and 30-day mortality, when controlling for patient demographics,
      comorbidities, American Society for Anesthesiologist (ASA) status, body mass
      index (BMI), and smoking status. RESULTS: A total of 13,685 cases were analyzed
      for 24 common foot and ankle operations. Overall mortality rate was 3.60%.
      Overall complication rate was 16.9%; 10.9% had medical and 8.3% had surgical
      complications. Residents were involved in 55.6% of cases. In unadjusted analyses,
      resident cases were less likely to be emergent, but were performed on more
      complicated patients (i.e. higher comorbidity burden, higher ASA scores).
      Resident cases had increased total morbidity (18.8% vs. 14.6%, p<0.001), medical
      complications (12.5% vs. 9.0%, p<0.001), and surgical complications (8.7% vs.
      7.7%, p=0.03), but similar mortality frequency (3.8% vs. 3.3%, p=0.2). In
      multivariable analyses, resident cases did not correlate with 30-day mortality,
      30-day total morbidity, or 30-day surgical complications; resident cases were,
      however, associated with increased medical complications [Odds Ratio (OR) 1.18
      (95% Confidence Interval (CI) 1.02-1.37, p=0.03)] and longer length of stay
      [Coeff 2.38 (1.68-3.09), p<0.001]. Subgroup analyses of orthopedic-only cases
      demonstrated no statistical association between resident involvement and
      mortality, total morbidity, or medical complications; a decrease in surgical
      complications was observed for open reduction internal fixation cases [OR 0.23
      (0.06-0.82), p=0.02]. CONCLUSIONS: Resident involvement in foot and ankle surgery
      is not associated with changes in 30-day mortality, 30-day total morbidity, or 30
      day surgical complication rates. Residents operate on more medically complex
      patients who experience higher medical complication rates and longer
      postoperative length of stay; however, the cause and directionality of this
      relationship remains to be determined. Efforts to improve the quality of foot and
      ankle surgery with resident involvement should target reductions in post
      operative medical complications. LEVEL OF EVIDENCE: Prognostic study, Level II.

PMID- 29202986
TI  - Arthrodesis of the first metatarsophalangeal joint-A biomechanical comparison of
      four fixation techniques.
AB  - BACKGROUND: Arthrodesis of the first metatarsophalangeal joint is a commonly
      performed orthopaedic procedure. The optimum method of fixation and joint surface
      preparation has yet to be determined. METHODS: This study compared four fixation
      techniques: Biomechanical grade sawbones were used. The dorsal plate used was a
      titanium, anatomically contoured locked plate. Testing was performed using an
      Instron machine applying force from the plantar aspect of the fused joint. Each
      fused sample was tested to failure. Stiffness, as calculated from the force
      displacement curve, and ultimate load tolerated were recorded for each sample.
      The method of failure of each sample was also documented. RESULTS: Constructs
      arthrodesed using dorsal plate with separate screw groups, regardless of method
      of joint preparation, were the stiffest (p<0.001). The weakest construct was
      dorsal plate alone without interfragmenary screw. There was no difference in
      stiffness between planar and cup-cone joint preparation (p=0.99). Maximum load
      tolerated was similar when comparing Crossed Screws with dorsal plate with screw
      with either cup-cone or planar reaming (p=0.93, p=0.89 respectively). Dorsal
      plating alone tolerated a significantly lower maximum load than Plate with Screw
      Groups or Crossed Screws (p<0.001). CONCLUSION: This study confirms that an IFS
      combined with a dorsally positioned locked-plate is the ideal construct, with the
      joint preparation technique of little consequence.

PMID- 29202987
TI  - Development and reliability of the Achilles Tendon Length Measure and comparison
      with the Achilles Tendon Resting Angle on patients with an Achilles tendon
      rupture.
AB  - BACKGROUND: There is a need for a valid, reliable, and easily applicable clinical
      measure of the length of the Achilles tendon (AT) after rupture. This study
      examines the reliability of a new ruler based measurement, the Achilles Tendon
      Length Measure (ATLM) in comparison with the goniometer-based Achilles Tendon
      Resting Angle (ATRA). METHODS: Measurements were performed by two independent
      physiotherapists eight weeks after AT rupture on 28 patients treated non
      operatively. RESULTS: The mean (SD) injured ATLM was 56.5 (2.3)cm, ICC2.1 0.91(CI
      [0.72-0.97]), SEM 0.7cm (SEM% 1.2), MDC 1.9cm (MDC% 3.4). Corresponding data for
      the injured ATRA was mean 64.4 degrees  (3.9 degrees ), ICC2.1 0.84 (CI [0.68-0
      92]), SEM 1.5 degrees  (SEM% 2.4), MDC 4.3 degrees  (MDC% 6.6). CONCLUSION: Both
      ATLM and ATRA showed excellent inter-rater reliability with low measurement
      error. Both measurements seem easy to use in clinical practice and potentially
      providing an indirect measure of the length of the AT after rupture.

PMID- 29202988
TI  - Mobile phone generated vibrations used to detect diabetic peripheral neuropathy.
AB  - BACKGROUND: In the current United Kingdom population the incidence of diabetic
      peripheral neuropathy is increasing. The presence of diabetic neuropathy affects
      decision making and treatment options. This study seeks to evaluate if the
      vibrations generated from a mobile phone can be used to screen patients for
      diabetic peripheral neuropathy. METHODS: This study comprised of 61 patients; a
      control group of 21 patients; a lower limb injury group of 19 patients; a
      diabetic peripheral neuropathy group of 21 patients. The control and injury group
      were recruited randomly from fracture clinics. The diabetic peripheral neuropathy
      group were randomly recruited from the diabetic foot clinic. The 61 patients were
      examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a
      vibrating mobile phone. The points tested were, index finger, patella, lateral
      malleoli, medial malleoli, heel, first and fifth metatarsal heads. RESULTS: The
      most accurate location of all the clinical tests was the head of the 1st
      metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten
      gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group
      felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The
      neuropathic group felt 216 of 441 tests (48%). There is a significant difference
      in the number of tests felt between the control and both the injury and
      neuropathic groups. p<0.0001 using N-1 Two Proportion Test. CONCLUSION: A mobile
      phone is an accurate screening tool for diabetic peripheral neuropathy. The most
      accurate location to test for diabetic peripheral neuropathy is the head of the
      1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger
      and patella were inaccurate. An injury to the lower limb affects the patient's
      vibration sensation, we would therefore recommend screening the contralateral
      limb to the injury. LEVEL OF EVIDENCE: This study represents level II evidence of
      a new diagnostic investigation.

PMID- 29202989
TI  - Cadaveric experiments to evaluate pressure wave generated by radial shockwave
      treatment of plantar fasciitis.
AB  - BACKGROUND: Shockwave treatment is increasingly used for plantar fasciitis and
      Achilles tendinopathy. To be effective it is believed that high pressure must be
      achieved in the tissues. We report on the first human cadaveric experiments to
      characterize pressure from radial shockwave therapy (rSWT) for plantar fasciitis.
      METHODS: The pressure from rSWT was measured in two cadaveric feet using a needle
      hydrophone. Maximal pressure and energy flux were calculated from the
      measurements. RESULTS: The pressure persisted longer than supposed, for up to
      400MUs. The peak negative pressure was up to two Mega Pascal. The predicted
      energy in the tissue strongly depended on the time interval used in calculations.
      CONCLUSIONS: The measured pressure may be sufficiently high to cause cavitation
      in the tissue, which is one of the proposed healing mechanisms associated with
      rSWT. The results suggest that the energy is imparted to the tissues for much
      longer than previously thought.

PMID- 29202990
TI  - Biological reconstruction of large osteochondral lesions of the talar dome with a
      modified "sandwich" technique-Midterm results.
AB  - BACKGROUND: Surgical treatment for large osteochondral lesions of the talar dome
      (OLTD) must restore the convexity and curvature of the talus. Here, we present
      midterm results and describe the modified "sandwich" reconstruction procedure.
      Bone defects were restored using a biological inlay consists of autologous bone
      chips that were mixed with bone marrow concentrate and fibrin glue and covered
      with a xenogeneic collagen membrane infiltrated with bone marrow concentrate and
      stabilized by fibrin glue. METHODS: Ten patients who were treated using a
      modified "sandwich" OLTD reconstruction were assessed after an average follow-up
      period of 46.4 (+/-18) months, using the clinical American Orthopaedic Foot and
      Ankle Society Ankle Hindfoot Scale (AOFAS) score and radiological magnetic
      resonance observation of cartilage repair tissue (MOCART) score. RESULTS: The
      mean AOFAS score increased significantly from 58.3 (+/-8.5) points to 81.8 (+/
      15.5) points as well the mean VAS score reduced significantly from 5.58 (+/-0.97)
      to 1.83 (+/-0.93) points. The average MOCART score was 69.5% (+/-16.7%) in the
      final follow-up. CONCLUSIONS: The presented modified "sandwich" technique
      permanently recreates the convexity and curvature in large osteochondral lesions
      of the talar dome with a single step surgical procedure.

PMID- 29202991
TI  - Osteochondral Lesions of the Talus Treatment With Fresh Frozen Allograft.
AB  - INTRODUCTION: Symptomatic talar osteochondral lesions are about 50% refractory to
      conservative treatment requiring a surgical solution. In the case of large
      chronic lesions, the use of bone graft taken from tissue bank is an alternative
      that enables to fill the defect without causing donor site morbidity. MATERIAL
      AND METHODS: Eight patients treated with talar osteochondral allograft in lesions
      greater than 20mm in diameter were analyzed - 4 males and 4 females aging 39.5
      years old on average. Evaluation was performed according to AOFAS scale and VAS
      as well as incorporation and continuation evaluations according to CT and MRI
      studies. A follow-up of 46.8 months on average was done. RESULTS: A 34.6-point
      improvement on average according to AOFAS. A 6.7-point pain improvement on
      average according to VAS. Incorporation in 100% of the cases. Two cases showed
      partial resorption and one case showed peri-graft lysis less than 30%. There was
      no collapse. CONCLUSIONS: Fresh frozen osteochondral allografts are a viable
      alternative when treating large osteochondral lesions, thereby avoiding morbidity
      of autologous donor areas or arthrodesis procedures.

PMID- 29202992
TI  - Beneficial clinical effects but limited tissue quality following osteochondral
      repair with a cell-free multilayered nano-composite scaffold in the talus.
AB  - BACKGROUND: The treatment of larger osteochondral lesions of the talus remains an
      operative challenge. In addition to micro fracturing and osteochondral
      transplantation one promising strategy could be the operative repair with a cell
      free multilayered nano-composite scaffold with the potential to regenerate bone
      and cartilage in one treatment. METHODS: In this prospective case series four
      consecutive patients who suffered from a single osteochondral lesion (>=1.5cm2)
      on the medial talus were enrolled. The repair potential of the implant was
      assessed using MRI based biochemical, compositional MR sequences (T2 mapping) as
      well as semi-quantitative morphological analyses (MOCART score) at 18 months
      follow-up after the surgery. The clinical outcome was determined at 6-, 12-, 18-,
      and 24 months follow-up by using the Ankle Disability Index and the AOFAS score.
      RESULTS: At 18 months after the surgery, the clinical outcome was significantly
      improved compared to the preoperative baseline. Global T2 relaxation times of the
      repair tissue were significantly increased compared to the healthy control
      cartilage. CONCLUSIONS: Osteochondral repair with a cell-free, biomimetic
      scaffold provides good clinical, short-term results. However, biochemical MR
      imaging provides strong evidence for limited repair tissue quality at 18 months
      after the implantation. LEVEL OF EVIDENCE: IV.

PMID- 29202993
TI  - Wide-awake foot and ankle surgery: A retrospective analysis.
AB  - BACKGROUND: The "wide-awake" approach to foot and ankle surgery is characterized
      by a surgeon-administered mixture of local anesthetic and epinephrine. No
      tourniquet, sedation, or general anesthesia are required for surgery. This paper
      describes a retrospective survey of the initial patients to undergo wide-awake
      foot and ankle surgery at our center. METHODS: Thirty former wide-awake patients
      were surveyed about their perioperative anxiety, pain, and satisfaction. RESULTS:
      Twenty-seven of 30 patients (90%) completed the survey. Patients received a
      variety of forefoot, hindfoot, and lower leg procedures. In general, they
      reported a decrease in anxiety over the course of the perioperative period
      (p=0.005). Pain fell from the preoperative to the intraoperative period, then
      rose to preoperative levels during recovery (p<0.001). Most patients said that
      the surgery was better than expected (83%); would choose wide-awake surgery for a
      subsequent procedure (87%); and would recommend wide-awake surgery to someone who
      required surgery (88%). CONCLUSIONS: Results indicate that the wide-awake
      approach to foot and ankle surgery causes little discomfort to patients who
      receive many common procedures. The removal of hindfoot hardware under local
      anesthesia is contraindicated.

PMID- 29202994
TI  - Functional outcomes following surgical-site infections after operative fixation
      of closed ankle fractures.
AB  - BACKGROUND: To compare the functional outcomes between patients with and without
      postoperative surgical-site infection (SSI) after surgical treatment in closed
      ankle fractures. METHODS: Retrospective cohort study with prospective follow-up.
      Of 1011 treated patients, 959 were eligible for inclusion in a postal survey.
      Functional outcomes were assessed using three self-reported questionnaires.
      RESULTS: In total 567 patients responded a median of 4.3 years (range 3.1-6.2
      years) after surgery. In total 29/567 had an SSI. The mean Olerud and Molander
      Ankle Score was 19.8 points lower for patients with a deep SSI (p=0.02), the
      Lower Extremity Functional Scale score was 10.2 points lower (p<0.01) and the
      Self-Reported Foot & Ankle Questionnaire score was 5.0 points higher (p=0.10)
      than for those without an SSI, after adjusting for age, sex, smoking status,
      diabetes, physical status, fracture classification and duration of surgery.
      CONCLUSIONS: Patients with a deep SSI had worse long-term functional outcomes
      than those without an SSI.

PMID- 29202995
TI  - An evaluation of the Herscovici classification for fractures of the medial
      malleolus.
AB  - BACKGROUND: Despite its use in the literature, the application of the Herscovici
      classification system for medial malleolus fractures has not been evaluated.
      METHODS: We aimed to determine the reliability and accuracy of the Herscovici
      classification. The blinded radiographs of 130 patients were independently
      classified by four orthopaedic trauma surgeons. We held a consensus meeting where
      observers agreed on a final classification and this served as our reference
      standard. We used weighted kappa (kappa) coefficients of agreement. RESULTS:
      Twenty-four fractures (18%) were deemed unclassifiable. The classification system
      demonstrated moderate inter-observer reliability (kappa=0.54, 95% CI 0.40-0.68)
      but substantial reproducibility (kappa=0.64, 95% CI 0.51-0.79). Accuracy, when
      compared with the reference standard, was kappa=0.54 (95% CI 0.40-0.66).
      CONCLUSIONS: The obliquity of the fracture line, and fracture extension, created
      difficulty in classification in 26% of cases. 18% of our cases could not be
      classified by majority decision. Our results emphasise the challenges faced in
      classifying these fractures. Future work should focus on refining the Herscovici
      classification.

PMID- 29202996
TI  - Epidemiology of calcaneal fractures in Finland.
AB  - BACKGROUND: The purpose of this study was to assess the nationwide incidence (per
      100,000 person-years) of operative treatment and hospitalization due to calcaneal
      fractures (CF) in Finland. METHODS: The study was based on the Finnish National
      Hospital Discharge Register. All patients aged 18-years or older admitted to
      Finnish hospitals for primary treatment of CF in 1987-2012 were included.
      RESULTS: During the 26-year study period 5977 patients were hospitalized with
      main or secondary diagnosis of a CF. The incidence of hospitalization due to CF
      remained relatively stable: (12.5)/100,000 in men and 3.9/100,000 in women. The
      men were younger (median 43 years) than the women (median 61 years). CONCLUSIONS:
      The incidence of the hospitalization due to CF in Finland has remained at steady
      level during the past 26 years. The incidence of CF is three times higher in men.
      In 2012 22% of the fractures were operatively treated.

PMID- 29202997
TI  - Arthroscopic treatment of intra-artricularly localised pigmented villonodular
      synovitis of the ankle: 4 cases with long-term follow-up.
AB  - BACKGROUND CONTEXT: Pigmented villonodular synovitis (PVNS) is a rare, locally
      aggressive benign proliferative pathology of synovial tissue. Lesions are
      classified regarding location as diffuse or localised which are same as
      histologically. Intra-articularly localised type is relatively rare, especially
      in the ankle joint. Because of the high recurrence rate and aggressive nature,
      localised lesions should be excised totally. PURPOSE: We performed a
      retrospective study of 4 patients with intra-articularly localised PVNS in the
      ankle joint who were treated by total arthroscopic excision and evaluated for
      functional results and recurrence rate. STUDY DESIGN: Case series. PATIENT
      SAMPLE: The mean age of the patients was 27 (17-46) years at the time of
      arthroscopic surgery. The mean follow-up time was 33 (24-48) months. METHODS:
      Functional evaluation according to the Musculoskeletal Tumour Society Score was
      performed, and patients were evaluated for recurrence by MR imaging. RESULTS: In
      all patients, functional results were excellent and there was no recurrence.
      CONCLUSIONS: This study demonstrates that the intra-articularly localised PVNS
      can be successfully treated with arthroscopic procedures without recurrence.

PMID- 29202998
TI  - A rare cause of lateral ankle pain: A symptomatic talus secundarius.
AB  - The talus secundarius is one of the rarest accessory tarsal bones, being present
      in 0.01% of all ankles. It is located at the lateral side of the talus, distally
      to the tip of the fibula. Hitherto, only five cases of a symptomatic talus
      secundarius have been described in literature. We presented a case of bilateral
      symptomatic talus secundarius in a young gymnast. There was a difference in size
      of the two accessory bones. The large talus secundarius in the left ankle was
      fixated, in the right ankle the fragment was excised. Both excision and fixation
      in the presented patient led to satisfactory results, both in the short and long
      term outcome.

PMID- 29202999
TI  - Epithelioid sarcoma of the plantar fascia mimicking Morbus Ledderhose - A severe
      pitfall for clinical and histopathological misinterpretation.
AB  - Plantar fibromatosis, also known as Morbus Ledderhose, is a well known and
      frequently encountered disorder of the planta pedis. When conservative treatment
      fails, surgical therapy with complete resection is the therapeutical procedure of
      choice. Soft tissue sarcoma is a heterogeneous and rare malignant disease of the
      musculoskeletal system with over 50 histopathological subtypes which can
      potentially arise in any localization but is most commonly found at the
      extremities. Here, we report the case of an epithelioid sarcoma of the sole of
      the foot which was initially and repeatedly clinically and histopathologically
      misinterpreted as plantar fibromatosis, receiving insufficient resection and
      subsequently ending in amputation of the lower leg.

PMID- 29203000
TI  - Revision with suture-tape augmentation after failed collateral ligament
      reconstruction for chronic interphalangeal instability of the hallux.
AB  - Chronic varus instability or recurrent subluxation following isolated
      interphalangeal dislocation of the hallux is a rare injury. No consensus has been
      reached regarding the best joint-salvage procedure for patients with the failed
      collateral ligament reconstruction using tendon graft. We report a case who
      achieved satisfactory clinical outcome through a modified surgical procedure
      (revision collateral ligament reconstruction augmented with suture-tape).

PMID- 29203001
TI  - Technique using the modified rolling hitch for split peroneus brevis tendon
      transfer in lateral ankle stabilization.
AB  - We report our technique for split peroneus brevis lateral ankle stabilization
      using the modified rolling hitch for tendon graft fixation. Applying the modified
      rolling hitch for tendon grasping in this procedure was useful, and it could
      decrease the surgical time and avoid the tendon injury caused by the needle.

PMID- 29203002
TI  - Complete tendon Achilles rupture following injection of Aethoxysklerol
      (polidocanol) for the treatment of chronic Achilles tendinopathy.
AB  - Achilles tendinopathy can be a chronic disabling condition affecting both
      athletic and sedentary patients. Multiple new treatment approaches have
      developed, including shock wave therapy and various types of injection. One of
      the novel treatment methods used is the injection of Aethoxysklerol or
      polidocanol, a sclerosing substance injected under ultrasound guidance targeting
      areas of neovascularisation. We report the case of a 78-year-old lady who
      suffered a complete Achilles tendon rupture following injection of
      Aethoxysklerol. This is the first case of Achilles tendon rupture following
      Aethoxysklerol injection in isolation to our knowledge in the literature and the
      first published complication of this treatment.

PMID- 29203003
TI  - Long term follow-up and development of foot complaints in a surgically treated
      mirror foot-A case report and review of literature.
AB  - BACKGROUND: Mirror foot is a rare anomaly and limited long term follow-up
      information is available. METHODS: Seven years after operation a mirror foot
      patient returned with foot complaints and was evaluated using radiographs and
      clinical examination. A systematic literature search was conducted to study foot
      complaints in mirror feet. RESULTS: Different origins of foot pain were
      considered in our patient; tibia length difference, deformed talus and accessory
      osseous structures in the tarsal region. Literature search resulted in 118 mirror
      feet. Based on cases reporting osseous structures, 74.2% showed tibia
      abnormalities and 94.5% an abnormal tarsal region. Only three cases mentioned a
      normal talus. Nine cases reported a follow-up period of more than five years.
      CONCLUSION: Osseous abnormalities are not always visible at birth, but are often
      present. Therefore, detailed examination of the affected limb in mirror foot
      patients with foot pain is important, in order to localize the origin.

PMID- 29203004
TI  - Fatal crashes involving large numbers of vehicles and weather.
AB  - INTRODUCTION: Adverse weather has been recognized as a significant threat to
      traffic safety. However, relationships between fatal crashes involving large
      numbers of vehicles and weather are rarely studied according to the low
      occurrence of crashes involving large numbers of vehicles. METHOD: By using all
      1,513,792 fatal crashes in the Fatality Analysis Reporting System (FARS) data,
      1975-2014, we successfully described these relationships. RESULTS: We found: (a)
      fatal crashes involving more than 35 vehicles are most likely to occur in snow or
      fog; (b) fatal crashes in rain are three times as likely to involve 10 or more
      vehicles as fatal crashes in good weather; (c) fatal crashes in snow [or fog] are
      24 times [35 times] as likely to involve 10 or more vehicles as fatal crashes in
      good weather. If the example had used 20 vehicles, the risk ratios would be 6 for
      rain, 158 for snow, and 171 for fog. CONCLUSIONS: To reduce the risk of
      involvement in fatal crashes with large numbers of vehicles, drivers should slow
      down more than they currently do under adverse weather conditions. Driver deaths
      per fatal crash increase slowly with increasing numbers of involved vehicles when
      it is snowing or raining, but more steeply when clear or foggy. PRACTICAL
      APPLICATIONS: We conclude that in order to reduce risk of involvement in crashes
      involving large numbers of vehicles, drivers must reduce speed in fog, and in
      snow or rain, reduce speed by even more than they already do.

PMID- 29203006
TI  - Letter from the Editors.

PMID- 29203005
TI  - STEADI: CDC's approach to make older adult fall prevention part of every primary
      care practice.
AB  - INTRODUCTION: Primary care providers play a critical role in protecting older
      adult patients from one of the biggest threats to their health and independence
      falls. A fall among an older adult patient cannot only be fatal or cause a
      devastating injury, but can also lead to problems that can effect a patient's
      overall quality of life. METHODS: In response, the Centers for Disease Control
      and Prevention (CDC) developed the STEADI initiative to give health care
      providers the tools they need to help reduce their older adult patient's risk of
      a fall. RESULTS: CDC's STEADI resources have been distributed widely and include
      practical materials and tools for health care providers and their patients that
      are designed to be integrated into every primary care practice. CONCLUSION: As
      the population ages, the need for fall prevention efforts, such as CDC's STEADI,
      will become increasingly critical to safeguard the health of Americans. PRACTICAL
      APPLICATIONS: STEADI's electronic health records (EHRs), online trainings,
      assessment tools, and patient education materials are available at no-cost and
      can be downloaded online at www.cdc.gov/STEADI. Health care providers should look
      for opportunities to integrate STEADI materials into their practice, using a team
      based approach, to help protect their older patients.

PMID- 29203007
TI  - The 5th International Symposium on Naturalistic Driving Research.

PMID- 29203008
TI  - A validation of the low mileage bias using naturalistic driving study data.
AB  - INTRODUCTION: This paper evaluated the low mileage bias (LMB) phenomenon for
      senior drivers using data mined from the Second Strategic Highway Research
      Program (SHRP 2) Naturalistic Driving Study. Supporters of the LMB construct
      postulate that it is only those seniors who drive the lowest annual mileage who
      are primarily responsible for the increased crash rates traditionally attributed
      to this population in general. METHOD: The current analysis included 802
      participants, all aged 65 or older who were involved in 163 property damage and
      injury crashes, and deemed to be at-fault in 123 (75%) of those instances.
      Poisson regression models were used to evaluate the association between
      annualized mileage driven and crash risk. RESULTS: Results show that the crash
      rate for drivers with lower annualized mileage (i.e., especially for those
      driving fewer than approximately 3000miles per year) was significantly higher
      than that of drivers with higher annualized mileage, and that 25% of the overall
      sample were low- mileage drivers according to this criterion. Data were also
      evaluated by gender and meta-age group (i.e., younger-old: 65-74 and older-old:
      75-99), and the results were consistent across these sub-groups. CONCLUSIONS:
      This study provides strong support for the existence of the LMB. PRACTICAL
      APPLICATIONS: These results can help to reshape how transportation safety
      stakeholders view senior drivers in general and help them to focus their efforts
      on those seniors most in need of either risk-reducing countermeasures or
      alternative means of transportation.

PMID- 29203009
TI  - Motorcyclists' self-reported riding mileage versus actual riding mileage in the
      following year.
AB  - INTRODUCTION: Accurate motorcyclist mileage estimates are important because self
      evaluation of riding experience is related to riding behavior, the relationship
      of self-reported to actual or future mileage is necessary in targeting training
      and considering survey responses, and motorcycle crash statistics require
      accurate travel data. METHOD: This study collected real-world data from
      motorcyclists over the course of two months to two years per rider. This paper
      explores motorcyclists' self-reported annual riding mileage (obtained via pre
      study surveys) and the actual amount of riding during the study (based upon
      odometer readings and GPS data). RESULTS: Of the 91 riders who had been riding
      for at least a year before the study, significantly more (73%) rode less the
      following year than reported for the previous year. The recorded annualized
      mileage averaged 89% of the reported mileage from the previous year. Analyses
      based on estimated average annual mileage were similar to those using the
      previous year estimation, and the pattern held regardless of age group,
      motorcycle type, or gender. The exception was novice or returning riders, who
      tended to either significantly underestimate or increase actual mileage as they
      began (or continued) to ride. CONCLUSIONS: Motorcyclists' estimation of riding
      experience expressed as mileage may not be indicative of current or future
      mileage. PRACTICAL APPLICATIONS: Reliance on self-reported mileage during
      training to categorize groups, for interpretation of studies, or to develop
      motorcycle travel data and safety statistics may be unrealistic. Certainly any
      use of self-reported mileage should incorporate the concept that mileage
      overestimation seems likely. Because questions about previous year and average
      annual mileage may elicit similar responses, motorcyclist surveys should be
      constructed to prompt the most thoughtful responses in terms of mileage
      estimations. In general, reported mileage should not be relied upon as an
      accurate predictor of future actual mileage.

PMID- 29203011
TI  - Automated recognition of rear seat occupants' head position using KinectTM 3D
      point cloud.
AB  - INTRODUCTION: Child occupant safety in motor-vehicle crashes is evaluated using
      Anthropomorphic Test Devices (ATD) seated in optimal positions. However, child
      occupants often assume suboptimal positions during real-world driving trips. Head
      impact to the seat back has been identified as one important injury causation
      scenario for seat belt restrained, head-injured children (Bohman et al., 2011).
      There is therefore a need to understand the interaction of children with the
      Child Restraint System to optimize protection. METHOD: Naturalistic driving
      studies (NDS) will improve understanding of out-of-position (OOP) trends. To
      quantify OOP positions, an NDS was conducted. Families used a study vehicle for
      two weeks during their everyday driving trips. The positions of rear-seated child
      occupants, representing 22 families, were evaluated. The study vehicle -
      instrumented with data acquisition systems, including Microsoft KinectTM V1 -
      recorded rear seat occupants in 1120 driving 26 trips. Three novel analytical
      methods were used to analyze data. To assess skeletal tracking accuracy, analysts
      recorded occurrences where KinectTM exhibited invalid head recognition among a
      randomly-selected subset (81 trips). Errors included incorrect target detection
      (e.g., vehicle headrest) or environmental interference (e.g., sunlight). When
      head data was present, KinectTM was correct 41% of the time; two other algorithms
      - filtering for extreme motion, and background subtraction/head-based depth
      detection are described in this paper and preliminary results are presented.
      Accuracy estimates were not possible because of their experimental nature and the
      difficulty to use a ground truth for this large database. This NDS tested methods
      to quantify the frequency and magnitude of head positions for rear-seated child
      occupants utilizing KinectTM motion-tracking. RESULTS: This study's results
      informed recent ATD sled tests that replicated observed positions (most common
      and most extreme), and assessed the validity of child occupant protection on
      these typical CRS uses. SUMMARY: Optimal protection in vehicles requires an
      understanding of how child occupants use the rear seat space. This study explored
      the feasibility of using KinectTM to log positions of rear seated child
      occupants. Initial analysis used the KinectTM system's skeleton recognition and
      two novel analytical algorithms to log head location. PRACTICAL APPLICATIONS:
      This research will lead to further analysis leveraging KinectTM raw data - and
      other NDS data - to quantify the frequency/magnitude of OOP situations, ATD sled
      tests that replicate observed positions, and advances in the design and testing
      of child occupant protection technology.

PMID- 29203012
TI  - Fleet analysis of headway distance for autonomous driving.
AB  - INTRODUCTION: Modern automobiles are going through a paradigm shift, where the
      driver may no longer be needed to drive the vehicle. As the self-driving vehicles
      are making their way to public roads the automakers have to ensure the
      naturalistic driving feel to gain drivers' confidence and accelerate adoption
      rates. METHOD: This paper filters and analyzes a subset of radar data collected
      from SHRP2 with focus on characterizing the naturalistic headway distance with
      respect to the vehicle speed. RESULTS: The paper identifies naturalistic headway
      distance and compares it with the previous findings from the literature.
      CONCLUSION: A clear relation between time headway and speed was confirmed and
      quantified. A significant difference exists among individual drivers which
      supports a need to further refine the analysis. PRACTICAL APPLICATIONS: By
      understanding the relationship between human driving and their surroundings, the
      naturalistic driving behavior can be quantified and used to increase the adoption
      rates of autonomous driving. Dangerous and safety-compromising driving can be
      identified as well in order to avoid its replication in the control algorithms.

PMID- 29203010
TI  - Teen drivers' awareness of vehicle instrumentation in naturalistic research.
AB  - INTRODUCTION: Naturalistic driving methods require the installation of
      instruments and cameras in vehicles to record driving behavior. A critical, yet
      unexamined issue in naturalistic driving research is the extent to which the
      vehicle instruments and cameras used for naturalistic methods change human
      behavior. We sought to describe the degree to which teenage participants' self
      reported awareness of vehicle instrumentation changes over time, and whether that
      awareness was associated with driving behaviors. METHOD: Forty-two newly-licensed
      teenage drivers participated in an 18-month naturalistic driving study. Data on
      driving behaviors including crash/near-crashes and elevated gravitational force
      (g-force) events rates were collected over the study period. At the end of the
      study, participants were asked to rate the extent to which they were aware of
      instruments in the vehicle at four time points. They were also asked to describe
      their own and their passengers' perceptions of the instrumentation in the vehicle
      during an in-depth interview. The number of critical event button presses was
      used as a secondary measure of camera awareness. The association between self
      reported awareness of the instrumentation and objectively measured driving
      behaviors was tested using correlations and linear mixed models. RESULTS: Most
      participants' reported that their awareness of vehicle instrumentation declined
      across the duration of the 18-month study. Their awareness increased in response
      to their passengers' concerns about the cameras or if they were involved in a
      crash. The number of the critical event button presses was initially high and
      declined rapidly. There was no correlation between driver's awareness of
      instrumentation and their crash and near-crash rate or elevated g-force events
      rate. CONCLUSION: Awareness was not associated with crash and near-crash rates or
      elevated g-force event rates, consistent with having no effect on this measure of
      driving performance. PRACTICAL APPLICATIONS: Naturalistic driving studies are
      likely to yield valid measurements of driving behavior.

PMID- 29203013
TI  - Examining drivers' eye glance patterns during distracted driving: Insights from
      scanning randomness and glance transition matrix.
AB  - INTRODUCTION: Visual attention to the driving environment is of great importance
      for road safety. Eye glance behavior has been used as an indicator of distracted
      driving. This study examined and quantified drivers' glance patterns and features
      during distracted driving. METHOD: Data from an existing naturalistic driving
      study were used. Entropy rate was calculated and used to assess the randomness
      associated with drivers' scanning patterns. A glance-transition proportion matrix
      was defined to quantity visual search patterns transitioning among four main eye
      glance locations while driving (i.e., forward on-road, phone, mirrors and
      others). All measurements were calculated within a 5s time window under both cell
      phone and non-cell phone use conditions. RESULTS: Results of the glance data
      analyses showed different patterns between distracted and non-distracted driving,
      featured by a higher entropy rate value and highly biased attention transferring
      between forward and phone locations during distracted driving. Drivers in general
      had higher number of glance transitions, and their on-road glance duration was
      significantly shorter during distracted driving when compared to non-distracted
      driving. CONCLUSIONS: Results suggest that drivers have a higher scanning
      randomness/disorder level and shift their main attention from surrounding areas
      towards phone area when engaging in visual-manual tasks. PRACTICAL APPLICATIONS:
      Drivers' visual search patterns during visual-manual distraction with a high
      scanning randomness and a high proportion of eye glance transitions towards the
      location of the phone provide insight into driver distraction detection. This
      will help to inform the design of in-vehicle human-machine interface/systems.

PMID- 29203015
TI  - Crashes and near-crashes on horizontal curves along rural two-lane highways:
      Analysis of naturalistic driving data.
AB  - INTRODUCTION: Prior research has shown the probability of a crash occurring on
      horizontal curves to be significantly higher than on similar tangent segments,
      and a disproportionally higher number of curve-related crashes occurred in rural
      areas. Challenges arise when analyzing the safety of horizontal curves due to
      imprecision in integrating information as to the temporal and spatial
      characteristics of each crash with specific curves. METHODS: The second Strategic
      Highway Research Program(SHRP 2) conducted a large-scale naturalistic driving
      study (NDS),which provides a unique opportunity to better understand the
      contributing factors leading to crash or near-crash events. This study utilizes
      high-resolution behavioral data from the NDS to identify factors associated with
      108 safety critical events (i.e., crashes or near-crashes) on rural two-lane
      curves. A case-control approach is utilized wherein these events are compared to
      216 normal, baseline-driving events. The variables examined in this study include
      driver demographic characteristics, details of the traffic environment and
      roadway geometry, as well as driver behaviors such as in-vehicle distractions.
      RESULTS: Logistic regression models are estimated to discern those factors
      affecting the likelihood of a driver being crash-involved. These factors include
      high-risk behaviors, such as speeding and visual distractions, as well as curve
      design elements and other roadway characteristics such as pavement surface
      conditions. CONCLUSIONS: This paper successfully integrated driver behavior,
      vehicle characteristics, and roadway environments into the same model. Logistic
      regression model was found to be an effective way to investigate crash risks
      using naturalistic driving data. PRACTICAL APPLICATIONS: This paper revealed a
      number of contributing factors to crashes on rural two-lane curves, which has
      important implications in traffic safety policy and curve geometry design. This
      paper also discussed limitations and lessons learned from working with the SHRP 2
      NDS data. It will benefit future researchers who work with similar type of data.

PMID- 29203014
TI  - Teens' distracted driving behavior: Prevalence and predictors.
AB  - INTRODUCTION: Teen drivers' over-involvement in crashes has been attributed to a
      variety of factors, including distracted driving. With the rapid development of
      in-vehicle systems and portable electronic devices, the burden associated with
      distracted driving is expected to increase. The current study identifies
      predictors of secondary task engagement among teenage drivers and provides basis
      for interventions to reduce distracted driving behavior. We described the
      prevalence of secondary tasks by type and driving conditions and evaluated the
      associations between the prevalence of secondary task engagement, driving
      conditions, and selected psychosocial factors. METHODS: The private vehicles of
      83 newly-licensed teenage drivers were equipped with Data Acquisition Systems
      (DAS), which documented driving performance measures, including secondary task
      engagement and driving environment characteristics. Surveys administered at
      licensure provided psychosocial measures. RESULTS: Overall, teens engaged in a
      potentially distracting secondary task in 58% of sampled road clips. The most
      prevalent types of secondary tasks were interaction with a passenger,
      talking/singing (no passenger), external distraction, and texting/dialing the
      cell phone. Secondary task engagement was more prevalent among those with primary
      vehicle access and when driving alone. Social norms, friends' risky driving
      behaviors, and parental limitations were significantly associated with secondary
      task prevalence. In contrast, environmental attributes, including lighting and
      road surface conditions, were not associated with teens' engagement in secondary
      tasks. CONCLUSIONS: Our findings indicated that teens engaged in secondary tasks
      frequently and poorly regulate their driving behavior relative to environmental
      conditions. Practical applications: Peer and parent influences on secondary task
      engagement provide valuable objectives for countermeasures to reduce distracted
      driving among teenage drivers.

PMID- 29203016
TI  - Investigate moped-car conflicts in China using a naturalistic driving study
      approach.
AB  - PROBLEM: Mopeds are a popular transportation mode in Europe and Asia. Moped
      related traffic accidents account for a large proportion of crash fatalities. To
      develop moped-related crash countermeasures, it is important to understand the
      characteristics of moped-related conflicts. METHOD: Naturalistic driving study
      data were collected in Shanghai, China from 36 car drivers. The data included
      2,878h and 78,296km driven from 13,149 trips. Moped-car conflicts were identified
      and examined from the passenger car driver's perspective using kinematic trigger
      algorithms and manual video reduction. RESULTS: A total of 119 moped-car
      conflicts were identified, including 74 high g-force conflicts and 45 low g-force
      events. These conflicts were classified into 22 on-road configurations where both
      similarities and differences were found as compared to Western Countries. The
      majority of the conflicts occurred on secondary main roads and branch roads. Hard
      braking was the primary response that the car drivers made to these conflicts
      rather than hard steering. DISCUSSIONS: The identified on-road vehicle-moped
      conflict configurations in Shanghai, China may be attributed to the complicated
      traffic environment and risky behavior of moped riders. The lower prevalence of
      hard steering in Shanghai as compared to the United States may be due to the
      lower speeds at event onsets or less available steering space, e.g., less
      available shoulder area on Chinese urban roads. CONCLUSIONS: The characteristics
      of moped-car conflicts may impact the design of active safety countermeasures on
      passenger cars. The pilot data from Shanghai urban areas suggest that
      countermeasures developed for China may require some modifications to those
      developed for the United States and European countries, although this
      recommendation may not be conclusive given the small sample size of the study.
      Future studies with large samples may help better understand the characteristics
      of moped-car conflicts.

PMID- 29203017
TI  - Driver behavior analysis for right-turn drivers at signalized intersections using
      SHRP 2 naturalistic driving study data.
AB  - INTRODUCTION: Understanding driver behavior is important for traffic safety and
      operation, especially at intersections where different traffic movements
      conflict. While most driver-behavior studies are based on simulation, this paper
      documents the analysis of driver-behavior at signalized intersections with the
      SHRP 2 Naturalistic Driving Study (NDS) data. This study analyzes the different
      influencing factors on the operation (speed control) and observation of right
      turn drivers. METHOD: A total of 300 NDS trips at six signalized intersections
      were used, including the NDS time-series sensor data, the forward videos and
      driver face videos. Different factors of drivers, vehicles, roads and
      environments were studied for their influence on driver behavior. An influencing
      index function was developed and the index was calculated for each influencing
      factor to quantitatively describe its influencing level. The influencing index
      was applied to prioritize the factors, which facilitates development and
      selection of safety countermeasures to improve intersection safety. Drivers'
      speed control was analyzed under different conditions with consideration of the
      prioritized influencing factors. RESULTS: Vehicle type, traffic signal status,
      conflicting traffic, conflicting pedestrian and driver age group were identified
      as the five major influencing factors on driver observation. CONCLUSIONS: This
      research revealed that drivers have high acceleration and low observation
      frequency under Right-Turn-On-Red (RTOR), which constituted potential danger for
      other roadway users, especially for pedestrians. PRACTICAL APPLICATIONS: As speed
      has a direct influence on crash rates and severities, the revealed speed patterns
      of the different situations also benefit selection of safety countermeasures at
      signalized intersections.

PMID- 29203018
TI  - Driver speed selection and crash risk: Insights from the naturalistic driving
      study.
AB  - INTRODUCTION: This study investigates how speed limits affect driver speed
      selection, as well as the related crash risk, while controlling for various
      confounding factors such as traffic volumes and roadway geometry. Data from a
      naturalistic driving study are used to examine how driver speed selection varies
      among freeways with different posted speed limits, as well as how the likelihood
      of crash/near-crash events change with respect to mean speed and standard
      deviation. METHOD: Regression models are estimated to assess three measures of
      interest: the average speed of vehicles during the time preceding crash/near
      crash and baseline (i.e., normal) driving events; the variation in travel speeds
      leading up to each event as quantified by the standard deviation in speeds over
      this period; and the probability of a specific event resulting in a crash/near
      crash based on speed selection and other factors. RESULTS: Speeds were relatively
      stable across levels-of-service A and B, within a range of 1.5mph on average.
      Speeds were marginally lower (3.3mph) on freeways posted at 65mph versus 70mph.
      In comparison, speeds were approximately 10.2 to 13.4mph lower on facilities
      posted at 55mph or 60mph. Speeds were shown to be 2.5mph lower in rainy weather
      and 11mph lower under snow or sleet. CONCLUSIONS: Significant correlation was
      observed with respect to speed selection behavior among the same individuals.
      Mean speeds are shown to increase with speed limits. However, these increases are
      less pronounced at higher speed limits. Drivers tend to reduce their travel
      speeds in presence of junctions and work zones, under adverse weather conditions,
      and particularly under heavy congestion. Crash risk increased with the standard
      deviation in speed, as well as on vertical curves and ramp junctions, and among
      the youngest and oldest age groups of drivers.

PMID- 29203019
TI  - Using naturalistic driving study data to investigate the impact of driver
      distraction on driver's brake reaction time in freeway rear-end events in car
      following situation.
AB  - INTRODUCTION: The rear-end crash is one of the most common freeway crash types,
      and driver distraction is often cited as a leading cause of rear-end crashes.
      Previous research indicates that driver distraction could have negative effects
      on driving performance, but the specific association between driver distraction
      and crash risk is still not fully revealed. This study sought to understand the
      mechanism by which driver distraction, defined as secondary task distraction,
      could influence crash risk, as indicated by a driver's reaction time, in freeway
      car-following situations. METHOD: A statistical analysis, exploring the causal
      model structure regarding drivers' distraction impacts on reaction times, was
      conducted. Distraction duration, distraction scenario, and secondary task type
      were chosen as distraction-related factors. Besides, exogenous factors including
      weather, visual obstruction, lighting condition, traffic density, and
      intersection presence and endogenous factors including driver age and gender were
      considered. RESULTS: There was an association between driver distraction and
      reaction time in the sample freeway rear-end events from SHRP 2 NDS database.
      Distraction duration, the distracted status when a leader braked, and secondary
      task type were related to reaction time, while all other factors showed no
      significant effect on reaction time. CONCLUSIONS: The analysis showed that driver
      distraction duration is the primary direct cause of the increase in reaction
      time, with other factors having indirect effects mediated by distraction
      duration. Longer distraction duration, the distracted status when a leader
      braked, and engaging in auditory-visual-manual secondary task tended to result in
      longer reaction times. PRACTICAL APPLICATIONS: Given drivers will be distracted
      occasionally, countermeasures which shorten distraction duration or avoid
      distraction presence while a leader vehicle brakes are worth considering. This
      study helps better understand the mechanism of freeway rear-end events in car
      following situations, and provides a methodology that can be adopted to study the
      association between driver behavior and driving features.

PMID- 29203020
TI  - Evidence-based safety (EBS) management: A new approach to teaching the practice
      of safety management (SM).
AB  - INTRODUCTION: In safety management (SM), it is important to make an effective
      safety decision based on the reliable and sufficient safety-related information.
      However, many SM failures in organizations occur for a lack of the necessary
      safety-related information for safety decision-making. Since facts are the
      important basis and foundation for decision-making, more efforts to seek the best
      evidence relevant to a particular SM problem would lead to a more effective SM
      solution. Therefore, the new paradigm for decision-making named "evidence-based
      practice (EBP)" can hold important implications for SM, because it uses the
      current best evidence for effective decision-making. METHODS: Based on a
      systematic review of existing SM approaches and an analysis of reasons why we
      need new SM approaches, we created a new SM approach called evidence-based safety
      (EBS) management by introducing evidence-based practice into SM. RESULTS: It was
      necessary to create new SM approaches. A new SM approach called EBS was put
      forward, and the basic questions of EBS such as its definition and core were
      analyzed in detail. Moreover, the determinants of EBS included manager's
      attitudes towards EBS; evidence-based consciousness in SM; evidence sources;
      technical support; EBS human resources; organizational culture; and individual
      attributes. CONCLUSIONS: EBS is a new and effective approach to teaching the
      practice of SM. Of course, further research on EBS should be carried out to make
      EBS a reality. Practical applications: Our work can provide a new and effective
      idea and method to teach the practice of SM. Specifically, EBS proposed in our
      study can help safety professionals make an effective safety decision based on a
      firm foundation of high-grade evidence.

PMID- 29203021
TI  - Graduated driver licensing (GDL) in the United States in 2016: A literature
      review and commentary.
AB  - This is the sixth in a series of reviews of research on graduated driver
      licensing (GDL) published in the Journal of Safety Research, the present review
      covering the period mid-2012 through 2016. In the two decades since GDL programs
      began to be introduced on a widespread basis in the United States, a vast amount
      of research has been published. The current review discusses recent research and
      the present state of knowledge on the following topics: characteristics of the
      novice driver population; effects of GDL on crashes for ages 16-19; the learner
      and intermediate periods; night and passenger restrictions; cellphone laws; GDL
      for older novices; enforcement of GDL rules; and programs attempting to influence
      GDL compliance and safe driving practices in general. GDL stands out as a
      successful policy for reducing teen driver crashes and is worth building on to
      extend its benefits. Strengthening existing GDL programs has the most potential
      for producing further crash reductions.

PMID- 29203022
TI  - Promotion of alternative-sized personal protective equipment.
AB  - INTRODUCTION: With more diversity in the workforce, companies are producing PPE
      such as hard hats, safety glasses, coveralls, foot protection, and safety
      harnesses for a larger range of body shapes and sizes. However, gray literature
      reports suggest that barriers exist to getting alternate sized PPE from the
      manufacturer to the workers who need it. The purpose of this study is to
      determine the extent to which alternative-sized PPE is marketed. METHOD: A web
      based review of seven major manufacturers of PPE was conducted to determine: (a)
      whether or not they offer alternative-sized products, (b) if these products are
      clearly labeled, and (c) if images used to display PPE are representative of a
      diverse workforce. RESULTS: Of the seven PPE manufacturers investigated, six had
      at least one product that was marketed as gender and/or size alternatives
      however, alternative sizes were more common for larger body types. Alternative
      sized products rarely included size charts, and the models used to display PPE
      were overwhelmingly white males of average size. CONCLUSIONS: Despite the growing
      availability of alternative-sized PPE, it can be difficult to find these
      products, which suggests that they are rarely promoted or labeled as alternative
      sized. Our study indicates that companies should expand their product lines and
      more aggressively market and promote these items. Guidance on how to properly fit
      their products would also be extremely helpful to the end-user. PRACTICAL
      APPLICATIONS: Manufacturers could improve the availability of alternative-sized
      PPE and increase their promotion of these products on their websites and in their
      catalogs. Individual companies and safety professionals may assist in this
      process by demonstrating demand for alternative-sized PPE.

PMID- 29203023
TI  - Identifying compensatory driving behavior among older adults using the
      situational avoidance questionnaire.
AB  - INTRODUCTION: Driving self-regulation is considered a means through which older
      drivers can compensate for perceived declines in driving skill or more general
      feelings of discomfort on the road. One form of driving self-regulation is
      situational avoidance, the purposeful avoidance of situations perceived as
      challenging or potentially hazardous. This study aimed to validate the
      Situational Avoidance Questionnaire (SAQ, Davis, Conlon, Ownsworth, & Morrissey,
      2016) and identify the point on the scale at which drivers practicing
      compensatory avoidance behavior could be distinguished from those whose driving
      is unrestricted, or who are avoiding situations for other, non-compensatory
      reasons (e.g., time or convenience). METHOD: Seventy-nine Australian drivers
      (Mage=71.48, SD=7.16, range: 55 to 86years) completed the SAQ and were classified
      as a compensatory-restricted or a non-restricted driver based on a semi
      structured interview designed to assess the motivations underlying avoidance
      behavior reported on the SAQ. RESULTS: Using receiver-operator characteristic
      (ROC) analysis, the SAQ was found to have high diagnostic accuracy (sensitivity:
      85%, specificity: 82%) in correctly classifying the driver groups. Group
      comparisons confirmed that compensatory-restricted drivers were self-regulating
      their driving behavior to reduce the perceived demands of the driving task. This
      group had, on average, slower hazard perception reaction times, and reported
      greater difficulty with driving, more discomfort when driving due to difficulty
      with hazard perception skills, and greater changes in cognition over the past
      five years. CONCLUSIONS: The SAQ is a psychometrically sound measure of
      situational avoidance for drivers in baby boomer and older adult generations.
      PRACTICAL APPLICATIONS: Use of validated measures of driving self-regulation that
      distinguish between compensatory and non-compensatory behavior, such as the SAQ,
      will advance our understanding of the driving self-regulation construct and its
      potential safety benefits for older road users.

PMID- 29203024
TI  - Rage against the machine? Google's self-driving cars versus human drivers.
AB  - INTRODUCTION: Automated driving represents both challenges and opportunities in
      highway safety. Google has been developing self-driving cars and testing them
      under employee supervision on public roads since 2009. These vehicles have been
      involved in several crashes, and it is of interest how this testing program
      compares to human drivers in terms of safety. METHODS: Google car crashes were
      coded by type and severity based on narratives released by Google. Crash rates
      per million vehicle miles traveled (VMT) were computed for crashes deemed severe
      enough to be reportable to police. These were compared with police-reported crash
      rates for human drivers. Crash types also were compared. RESULTS: Google cars had
      a much lower rate of police-reportable crashes per million VMT than human drivers
      in Mountain View, Calif., during 2009-2015 (2.19 vs 6.06), but the difference was
      not statistically significant. The most common type of collision involving Google
      cars was when they got rear-ended by another (human-driven) vehicle. Google cars
      shared responsibility for only one crash. CONCLUSIONS: These results suggest
      Google self-driving cars, while a test program, are safer than conventional human
      driven passenger vehicles; however, currently there is insufficient information
      to fully examine the extent to which disengagements affected these results.
      PRACTICAL APPLICATION: Results suggest that highly-automated vehicles can perform
      more safely than human drivers in certain conditions, but will continue to be
      involved in crashes with conventionally-driven vehicles.

PMID- 29203025
TI  - Demographic determinants of chemical safety information recall in workers and
      consumers in South Africa: A cross sectional study.
AB  - BACKGROUND: Chemical hazard communication is intended to alert users of the
      potential hazards of chemicals. Hazard information needs to be understood and
      recalled. Recall of hazard communication is critical when the written form of the
      information is not available at the time it is required. METHODS: A cross
      sectional study investigating associations between recall of chemical safety
      information on labels amongst 402 participants including 315 workers and 87
      consumers in two provinces of South Africa. RESULTS: Respondents were
      predominantly male (67.7%), the median age was 37 years (IQR: 30-46years) and
      less than half of the participants completed high school (47.5%). Multivariate
      analysis identified the following positive associations with the recall of all
      the label elements listing the strongest association: call appropriate services
      and industrial vs consumer sector (OR=2.4; 95% CI: 1.2; 4.6 ); call appropriate
      services and transport vs consumer sector (OR=4.4; 95% CI: 1.2; 16.0); flammable
      symbol and male vs female gender (OR=2.3; 95% CI: 1.0; 5.3); flammable symbol and
      home language English vs African languages (OR=6.6; 95% CI: 2.1; 21.2); any
      hazard statement and home language Afrikaans vs African languages (OR=14.0; 95%
      CI: 3.6; 54.2), any first aid statement and further education vs none (OR=3.3;
      95% CI: 1.3; 8.0), correct chemical name and industry blue collar workers vs non
      industry blue collar workers (OR=2.6; 95% CI: 1.1; 6.1), correct chemical name
      and non-industry white collar occupations vs non-industry blue collar workers
      (OR=2.7; 95% CI: 1.0; 7.1). CONCLUSION: The study found a number of potential
      positive associations which influence recall of label elements of which some
      (e.g., sector, gender, occupation) suggest further research. Relevant policies in
      South Africa should ensure that the safety information on chemical labels is
      clearly visible to read and understandable which aids recall and the reduction in
      harmful chemical exposures.

PMID- 29203026
TI  - Perceptions of alcohol-impaired driving and the blood alcohol concentration
      standard in the United States.
AB  - INTRODUCTION: Although the number of alcohol-impaired driving (AID) fatalities
      has declined over the past several years, AID continues to be a serious public
      health problem. The purpose of this effort was to gain a better understanding of
      the U.S. driving population's perceptions and thoughts about the impacts of
      lowering the blood alcohol concentration (BAC) driving standard below.08% on AID,
      health, and other outcomes. METHODS: A questionnaire was administered to a
      nationally representative sample of licensed drivers in the U.S. (n=1011) who
      were of age 21 or older on driving habits, alcohol consumption habits, drinking
      and driving habits, attitudes about drinking and driving, experiences with and
      opinions of drinking and driving laws, opinions about strategies to reduce
      drinking and driving, general concerns about traffic safety issues, and
      demographics. RESULTS: One-third of participants supported lowering the legal BAC
      standard, and participants rated a BAC standard of .05% to be moderately
      acceptable on average. 63.9% indicated that lowering 30 the BAC to .05% would
      have no effect on their decisions to drink and drive. Nearly 60% of respondents
      lacked accurate knowledge of their state's BAC standard. CONCLUSIONS: Public
      support for lowering the BAC standard was moderate and was partially tied to
      beliefs about the impacts of a change in the BAC standard. The results suggest
      that an opportunity for better educating the driving population about existing
      AID policy and the implications for lowering the BAC level on traffic injury
      prevention. PRACTICAL APPLICATIONS: The study results are useful for state
      traffic safety professionals and policy makers to have a better understanding of
      the public's perceptions of and thoughts about BAC standards. There is a clear
      need for more research into the effects of lowering the BAC standard on crashes,
      arrests, AID behavior, and alcohol-related behaviors.

PMID- 29203027
TI  - Thrill and adventure seeking in risky driving at work: The moderating role of
      safety climate.
AB  - Introduction Within many industrialized countries, the leading cause of worker
      fatalities and serious injuries can be attributed to road trauma. In non
      occupational research, high levels of sensation seeking personality, and
      specifically thrill and adventure seeking, have been associated with risky
      driving behaviors. In work driving literature, high organizational safety climate
      has been associated with reduced risky driving in work drivers. However, the
      extent that factors such as safety climate and thrill seeking interact in regard
      to work driving safety remains unclear, and the current research examined this
      interaction. Methods A total of 1,011 work drivers from four organizations
      participated in the research. Surveys were distributed online and hardcopies were
      sent via mail. The survey included measures of thrill and adventure seeking,
      safety climate and work-related driving behaviors, as well as questions relating
      to participant demographics and information about their work driving. Results The
      results demonstrated that safety climate significantly moderated the effect of
      thrill and adventure seeking trait on driving errors, driving violations, and
      driving while fatigued. Conclusion These results suggest that the development of
      a strong safety climate has the potential to improve work driving safety outcomes
      by reducing the impact of particular personality traits such as thrill seeking
      within an organizational context. Practical application To improve work driving
      safety, organizations and management need to develop strategies to encourage and
      foster positive work driving safety climate, particularly within work settings
      that may attract thrill and adventure seeking employees.

PMID- 29203028
TI  - Investigating ethnic minorities' perceptions of safety climate in the
      construction industry.
AB  - INTRODUCTION: An increasing number of ethnic minorities (EMs) have been employed
      in the construction industry to alleviate severe labor shortages in many
      countries. Unfortunately, statistics show that EMs have higher fatal and non
      fatal occupational injury rates than their local counterparts. However, EMs are
      often underrepresented in safety climate (SC) research as they are difficult to
      reach and gauge their perception. A positive relationship has been widely found
      between SC and safety performance. Understanding the safety perceptions of EMs
      helps to reduce injuries and improve their safety performance. METHOD: Based on a
      sample of 320 EMs from 20 companies in the construction industry, exploratory
      factor analysis (EFA) and confirmatory factor analysis (CFA) were used to
      identify the SC factors of EMs, and validate the extracted factors, respectively.
      Multivariate analysis of variance was undertaken to examine mean differences in
      perceptions of SC by personal characteristics. RESULTS: Three SC factors for EMs
      encapsulating 16 variables were identified through EFA. The hypothesized CFA
      model for a three-factor structure derived from EFA showed a satisfactory
      goodness-of-fit, composite reliability, and construct validity. CONCLUSIONS:
      Three SC factors were identified, namely: (a) safety management commitment,
      safety resources, and safety communication; (b) employee's involvement and
      workmate's influence; and (c) perception of safety rules, procedures and risks.
      The perceptions of SC differed significantly by nationality, marital status, the
      number of family members supported, and drinking habit. PRACTICAL APPLICATIONS:
      This study reveals the perception of EMs toward SC. The findings highlight the
      areas for safety improvement and provide leading indicators for safety
      performance of EMs. The findings are also enlightening for countries with a
      number of EMs, such as the United Sates, the United Kingdom, Australia,
      Singapore, and the Middle East.

PMID- 29203029
TI  - Modeling pedestrian gap crossing index under mixed traffic condition.
AB  - INTRODUCTION: There are a variety of challenges faced by pedestrians when they
      walk along and attempt to cross a road, as the most recorded accidents occur
      during this time. Pedestrians of all types, including both sexes with numerous
      aging groups, are always subjected to risk and are characterized as the most
      exposed road users. The increased demand for better traffic management strategies
      to reduce the risks at intersections, improve quality traffic management, traffic
      volume, and longer cycle time has further increased concerns over the past
      decade. METHOD: This paper aims to develop a sustainable pedestrian gap crossing
      index model based on traffic flow density. It focusses on the gaps accepted by
      pedestrians and their decision for street crossing, where (Log-Gap) logarithm of
      accepted gaps was used to optimize the result of a model for gap crossing
      behavior. Through a review of extant literature, 15 influential variables were
      extracted for further empirical analysis. Subsequently, data from the observation
      at an uncontrolled mid-block in Jalan Ampang in Kuala Lumpur, Malaysia was
      gathered and Multiple Linear Regression (MLR) and Binary Logit Model (BLM)
      techniques were employed to analyze the results. RESULTS AND CONCLUSIONS: From
      the results, different pedestrian behavioral characteristics were considered for
      a minimum gap size model, out of which only a few (four) variables could explain
      the pedestrian road crossing behavior while the remaining variables have an
      insignificant effect. Among the different variables, age, rolling gap, vehicle
      type, and crossing were the most influential variables. The study concludes that
      pedestrians' decision to cross the street depends on the pedestrian age, rolling
      gap, vehicle type, and size of traffic gap before crossing. PRACTICAL
      APPLICATIONS: The inferences from these models will be useful to increase
      pedestrian safety and performance evaluation of uncontrolled midblock road
      crossings in developing countries.

PMID- 29203030
TI  - Attitudes toward mandatory ignition interlocks for all offenders convicted of
      driving while intoxicated.
AB  - INTRODUCTION: Ignition interlocks are effective in reducing alcohol-impaired
      driving recidivism for all offenders, including first-time offenders. Despite
      their effectiveness, interlock use among persons convicted of driving while
      intoxicated from alcohol (DWI) remains low. This cross-sectional survey of U.S.
      adults assessed public support for requiring ignition interlocks for all
      convicted DWI offenders including first-time offenders. The goal was to update
      results from a similar 2010 survey in light of new state requirements and
      increased interlock installations. METHODS: Questions were included in the Porter
      Novelli FallStyles survey, which was fielded from September 28 to October 16,
      2015. Participants were the 3,536 individuals who provided an opinion toward
      requiring ignition interlocks for all offenders. For analyses, opinion toward
      requiring interlocks for all offenders was dichotomized into 'agree' and
      'neutral/disagree.' To handle missing data, 10 imputed datasets were created and
      pooled using fully conditional specification (FCS). RESULTS: Fifty-nine percent
      of adults supported requiring interlocks for all DWI offenders. Multivariate
      analysis revealed that persons who did not report alcohol-impaired driving (AID)
      were 60% more likely to support requiring interlocks than those who reported AID.
      Having heard of interlocks also increased support. Support was generally
      consistent across demographic subgroups. CONCLUSIONS: Interlocks for all
      offenders have majority support nationwide in the current survey, consistent with
      previous reports. Support is lowest among those who have reported alcohol
      impaired driving in the past 30days. These results suggest that communities with
      higher levels of alcohol-impaired driving may be more resistant to requiring
      ignition interlocks for all convicted DWI offenders. Future studies should
      examine this association further. Practical applications: These results indicate
      that the majority of adults recognize DWI as a problem and support requiring
      interlocks for all offenders.

PMID- 29203031
TI  - The clinical anatomy of the temporal and parietal lobes.

PMID- 29203032
TI  - Detection and prediction of driver drowsiness using artificial neural network
      models.
AB  - Not just detecting but also predicting impairment of a car driver's operational
      state is a challenge. This study aims to determine whether the standard sources
      of information used to detect drowsiness can also be used to predict when a given
      drowsiness level will be reached. Moreover, we explore whether adding data such
      as driving time and participant information improves the accuracy of detection
      and prediction of drowsiness. Twenty-one participants drove a car simulator for
      110min under conditions optimized to induce drowsiness. We measured physiological
      and behavioral indicators such as heart rate and variability, respiration rate,
      head and eyelid movements (blink duration, frequency and PERCLOS) and recorded
      driving behavior such as time-to-lane-crossing, speed, steering wheel angle,
      position on the lane. Different combinations of this information were tested
      against the real state of the driver, namely the ground truth, as defined from
      video recordings via the Trained Observer Rating. Two models using artificial
      neural networks were developed, one to detect the degree of drowsiness every
      minute, and the other to predict every minute the time required to reach a
      particular drowsiness level (moderately drowsy). The best performance in both
      detection and prediction is obtained with behavioral indicators and additional
      information. The model can detect the drowsiness level with a mean square error
      of 0.22 and can predict when a given drowsiness level will be reached with a mean
      square error of 4.18min. This study shows that, on a controlled and very
      monotonous environment conducive to drowsiness in a driving simulator, the
      dynamics of driver impairment can be predicted.

PMID- 29203033
TI  - Recessive Dystrophic Epidermolysis Bullosa and Pregnancy.
AB  - Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations
      in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis
      bullosa) is characterized by the absence or considerably reduced expression of
      type VII collagen, which leads to marked fragility of the skin and mucous
      membranes and subsequent blister formation, whether spontaneously or following
      minimal injury. There have been very few reports of this disease in pregnant
      women. We present 2 cases of pregnant women with recessive dystrophic
      epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital
      Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean
      delivery, with no further complications for mother or child. Although recessive
      dystrophic epidermolysis bullosa increases the risk of maternal complications, a
      patient is not advised against pregnancy. With adequate monitoring, these
      patients can fulfil their desire to become mothers.

PMID- 29203034
TI  - Atypical Presentation of Herpes Simplex Virus Type 2 Infection Refractory to
      Treatment With Acyclovir in 2 Hematologic Patients.
AB  - Herpesvirus infections are not uncommon in hematologic patients. Our first
      patient, diagnosed with chronic lymphatic leukemia, presented extensive genital
      herpes infection refractory to treatment with acyclovir and with a partial
      response to foscarnet, which had to be withdrawn due to systemic adverse effects.
      The second patient, diagnosed with follicular Hodgkin lymphoma, presented
      hypertrophic herpes infection refractory to treatment with acyclovir but that
      responded to intralesional cidofovir and topical imiquimod. As in other
      immunodepressed patients, herpesvirus infection in hematologic patients can
      present atypical manifestations, as well as resistance to treatments that act via
      the viral thymidine kinase. A high level of clinical suspicion is therefore
      needed to make an early diagnosis, together with extensive knowledge of the
      different treatments available.

PMID- 29203035
TI  - [Perspective of the transition from reusable instruments to single use ancillary
      in orthopedic surgery].
AB  - OBJECTIVES: Since 2009, single-use (SU) ancillaries for total knee arthroplasty
      (TKA) and total hip arthroplasty (THA) have been marketed to replace reusable
      ancillaries. The concept is not innovative but their use in orthopedics is still
      uncommon. An assessment has been done for the use of SU ancillary in Assistance
      publique-hopitaux de Paris with the consequences for the patient, the surgeon and
      the hospital. METHODS: A technical and a clinical review has been done with those
      devices in 2015. The economic and organizational impacts were identified and
      submitted for opinion to committee experts in orthopedics. RESULTS: Three SU
      ancillaries are commercialized. No clinical studies are currently available.
      There is no reimbursement for SU ancillaries whereas reusable ancillaries are
      included in prosthesis reimbursement price. Although SU ancillaries (TKA and THA)
      saving costs for sterilization, the annual additional budget estimated for their
      purchase would approximately be 2.5 times higher. Nevertheless, indirect savings
      could be also considered in the long-term period (global costs for sterilization,
      volume effect...). For the same quality, according to the experts, organizational
      impacts are low for the patient and the surgeon but potentially important for the
      hospital, the nursing and pharmaceutical staff, and logistical activities.
      CONCLUSIONS: On logistic, clinical and financial aspects, SU ancillaries need
      more evaluation. The switch to SU ancillaries allows saving sterilization costs
      and time, and provided an immediate mobilization of the equipment but their
      interest must be demonstrated by clinical and economic data.

PMID- 29203036
TI  - Comparison of the Prognostic Usefulness of the European Society of Cardiology and
      American Heart Association/American College of Cardiology Foundation Risk
      Stratification Systems for Patients With Hypertrophic Cardiomyopathy.
AB  - Implantable cardiodefibrillators (ICDs) have proven benefit in preventing sudden
      cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk
      stratification essential. Data on the predictive accuracy on the European Society
      of Cardiology (ESC) risk scoring system have been conflicting. We independently
      evaluated the ESC risk scoring system in our cohort of patients with HC from a
      large tertiary center and compared this with previous guidance by the American
      College of Cardiology Foundation and Heart Association (ACCF/AHA). Risk factor
      profiles, 5-year SCD risk estimates, and ICD recommendations, as defined by the
      ACCF/AHA and ESC guidelines, were retrospectively ascertained for 288 HC patients
      with and without SCD or equivalent events at our center. In the SCD group (n =
      14), a significantly higher proportion of patients would not have met the
      criteria for an ICD implant using the ESC scoring algorithm compared with
      ACCF/AHA guidance (43% vs 7%, p = 0.029). In those without SCD events (n = 274),
      a larger proportion of individuals not requiring an ICD was identified using the
      ESC risk score model compared with the ACCF/AHA model (82% vs 57%; p < 0.0001).
      Based on risk stratification criteria alone, 5 more individuals with a previously
      aborted SCD event would not have received an ICD with the ESC risk model compared
      with the ACCF/AHA risk model. In conclusion, we found that the current ESC
      scoring system potentially leaves more high-risk patients unprotected from sudden
      death in our cohort of patients.

PMID- 29203037
TI  - Near infrared perfusion assessment of gastric conduit during minimally invasive
      Ivor Lewis esophagectomy.
AB  - INTRODUCTION: Anastomotic leak and conduit necrosis are devastating complications
      following Ivor Lewis esophagectomy. Near infrared imaging (NIR) using IndoCyanine
      Green allows for real time tissue perfusion assessment which may reduce
      anastomotic leak during minimally invasive Ivor Lewis esophagectomy (MIE).
      METHODS: Forty consecutive MIE were performed by a single surgeon at a tertiary
      referral center. The first 20 were assessed for gastric conduit perfusion by
      clinical criteria (Group 1). The second 20 were also assessed using NIR
      laparoscopic system (Group 2). RESULTS: Comparing Group 1 to Group 2, no
      significant differences were found in overall complication rate, readmission or
      reoperation rate. NIR resulted in resection of the non perfused proximal portion
      of the conduit in 30% (6/20). Two patients in group 2 group developed anastomotic
      leak (2/20) compared to 0 in Group 1 (p = 0.49). Graft necrosis led to one
      mortality in Group 1, while there were 0 mortalities in Group 2. (p = 1.0).
      CONCLUSION: Although NIR plays a role in assessment of tissue perfusion, in our
      study its use did not result in reduction of anastomotic leak rate.

PMID- 29203038
TI  - Trends in Medicaid beneficiaries' receipt of breast reconstruction procedures
      following Pre-Affordable Care Act (ACA) Medicaid expansion in New York State.
AB  - BACKGROUND: Expanding eligibility will increase the demand for surgical services
      within Medicaid but little is known of the response to such increase in demand.
      We examined how much of the increased demand for breast reconstruction was met
      after expansion of Medicaid eligibility. METHODS: We used New York state
      databases from 1998 to 2006 and a population of non-elderly adults (19-64) who
      underwent breast cancer treatment and reconstructive procedures. We used an
      Interrupted Time-Series design to examine the association between Medicaid
      expansion in 2001 and changes in the percentages of treatment and reconstructive
      procedures covered by Medicaid. RESULTS: After expansion, there was an increase
      of 9.6% in the percentage of treatment procedures covered by Medicaid (added
      demand for breast reconstruction). However, there was a 6.8% increase in the
      percentage of reconstructive procedures covered by Medicaid. CONCLUSIONS: The
      smaller increase in Medicaid percentage of reconstructive procedures suggests
      that the added demand for reconstruction was not met.

PMID- 29203039
TI  - [Vascular calcification in pseudoxanthoma elasticum in children].
AB  - INTRODUCTION: Vascular calcifications are associated with several diseases that
      affect vascular connective tissue and skin and cause considerable morbidity and
      mortality. The prototype of these conditions is pseudoxanthoma elasticum. We
      report, in this study, 4 pediatric cases of vascular calcifications diagnosed as
      elastic pseudoxanthoma. OBSERVATIONS: These 4 children were 2-11 years old and
      presented variable clinical features. Vascular involvement and arterial
      hypertension was observed in all patients, skin involvement in 2 cases,
      gastrointestinal involvement in 2 cases, neurological impairment in one case, and
      cardiac involvement in one case. Demonstration of ABCC6 gene mutations provided
      diagnostic confirmation in all cases. CONCLUSION: Pseudoxanthoma elasticum is a
      rare genetic disease, which can lead to many complications. Appropriate knowledge
      and early diagnosis are essential.

PMID- 29203040
TI  - [Management of traumatic and iatrogenic arterial pseudoaneurysms in a tropical
      environment].
AB  - A false aneurysm or pseudoaneurysm (PA) is the formation of a pulsatile and
      encapsulated hematoma in communication with the lumen of a perforated artery. Its
      origin is different but most cases are associated with a traumatic event.
      Currently, the referenced treatment is endovascular surgery but it is not
      feasible for the majority of vascular surgeons working in a tropical environment.
      The aim of this study was to describe the diagnostic and therapeutic aspects of
      arterial PA (APA) encountered in our institution and to evaluate the place of
      open surgical technique in their management. This was a 30-month retrospective
      and descriptive study carried out in our institution (CHU-JRA, Antananarivo,
      Madagascar). Between 2012 and 2014, ten cases of APA were operated. There were 8
      men with an average age of 30 years. The etiologies were accidental trauma (n=6)
      or iatrogenic vascular injury (n=4). Most patients had a painful and pulsatile
      swelling (n=8). The presence of a wound scar located on the swelling was observed
      in 5 patients. The false aneurysms were localized in the radial (n=3), femoral
      (n=2), brachial (n=2), carotid (n=2) and ulnar (n=1) arteries. The diagnosis was
      confirmed by ultrasound Doppler in all patients. The treatment was an open
      surgical procedure and consisted of lateral suture (n=4), resection with direct
      end-to-end anastomosis (n=1) or using autologous saphenous vein graft (n=2) or
      ligation (n=3). Postoperative courses and outcomes at last follow-up were
      uneventful with optimal patency rate.

PMID- 29203041
TI  - [Management of isolated iliac aneurysms: A Tunisian center experience].
AB  - Isolated aneurysms of the iliac arteries are rare. The diagnoses of these
      aneurysms become easier with non-invasive radiologic investigations. The
      development of endovascular treatment is a recent alternative to surgical
      treatment. We report our experience in the management of 8 cases of isolated
      iliac aneurysms in the department of cardiovascular and thoracic surgery of the
      Habib Bourguiba Hospital of Sfax.

PMID- 29203042
TI  - [Treatment of radiation-induced iliofemoral arterial complications with groin
      radionecrosis].
AB  - Long-term iliofemoral complications induced by radiation include vascular
      (arterial and venous) lesions, nervous lesions and soft tissue loss that can be
      cutaneous and subcutaneous and potentially lead to radionecrosis with vessel
      exposure. We present five cases of groin radionecrosis. There were three men and
      two women (age 30-73 years). Radiotherapy had been delivered 15 years earlier in
      three cases, and 2 years earlier in two cases. Symptoms were intermittent
      claudication (n=1), critical ischemia (n=1), and septic hemorrhage (n=1). Two
      patients had no vascular symptoms. Four patients underwent scheduled surgery
      after complete cardiac and cardiovascular evaluation with duplex-Doppler, CT scan
      and/or intra-arterial angiography. One woman underwent emergency surgery after
      septic hemorrhage of a previous in situ femoral revascularization fashioned 2
      months earlier. Revascularization was achieved with trans-iliac (n=3), trans
      muscular (n=1, and in situ (n=1) iliofemoral bypass. A retroperitoneal approach
      with section of large muscles was used. In three cases, a trans-iliac route was
      used by perforating the iliac wing with a 8-mm PTFE graft. Proximal anastomosis
      was done on the abdominal aorta (n=1) and the homolateral common iliac artery
      (n=2). Distal anastomosis was done on the distal profunda artery and popliteal
      artery (n=1) and on the distal femoral superficial artery (n=2). In two cases, an
      iliofemoral bypass was done with a 7-mm PTFE vascular graft. The proximal
      anastomosis was done on the proximal external iliac artery and the distal
      anastomosis on the proximal superficial femoral artery. A plastic procedure was
      performed in four cases. Three patients had a homolateral (n=1) or controlateral
      (n=2) rectus abdominis flap. In one case, plastic coverage was done with an
      antebrachial flap (Chinese flap), which has been released at 6 weeks. One patient
      had post-radiotherapy iliofemoral vascular disease, but there was no vascular
      exposure, and no plastic coverage was necessary. The postoperative course was
      uneventful in four cases. The patient treated with an in situ bypass developed
      septic hemorrhage at day 10, requiring revision. The patient died of multiple
      organ system failure, with a patent graft and a viable flap. The other four
      patients had no early or late complications. These patients have been followed
      annually for clinical examinations and duplex scans, and angio-scans. One patient
      died of ischemic heart disease. The three other patients are alive with a patent
      bypass with 11, 8 and 3 years follow-up. One patient had a late occlusion of the
      bypass treated by thrombectomy after 7 and 10 years. In conclusion, patients with
      femoral radionecrosis can be treated by an extra-anatomic bypass, with plastic
      coverage. The trans-iliac is a relatively simple and safe procedure.

PMID- 29203043
TI  - [Blood pressure target in 2017].
AB  - OBJECTIVE: The issue of how far blood pressure (BP) should be lowered under
      antihypertensive treatment is still an important matter of scientific debate. The
      aim of the present review is to consider the clinical relevance of individualized
      BP goal under treatment in hypertensive patients according to their age,
      comorbidities or established cardio-vascular (CV) disease. DATA FROM THE
      LITERATURE: The French and European recommendations propose a systolic BP target
      between 130 and 139mmHg (<150mmHg after 80 years) and diastolic BP target <90mmHg
      in hypertensive patients whatever their level of risk. The results of the recent
      SPRINT study suggest that a more ambitious systolic BP target, <120mmHg,
      significantly reduces CV morbidity and mortality, but with an increased
      iatrogenic risk. Several questions in everyday practice have to be considered. An
      important issue concerns BP measurement methods in this clinical trial (Dinamap)
      versus in routine clinical practice and the implications on BP treatment targets.
      In addition, close monitoring of participants in clinical trials and active
      orthostatic hypotension research limit the incidence of adverse events related to
      intensive treatement. Finally, in the presence of an established CV disease, an
      intensive therapeutic approach could be associated with a J-curve relationship
      between BP level and CV events. CONCLUSION: An early and strict BP control in
      young or middle-aged hypertensive patients in primary prevention should be a
      priority. In this hypertensive population with low to moderate CV risk, without
      established CV or renal diseases, more stringent than recommended BP-lowering
      treatment could potentially prevent hypertensive arterial damage and thus correct
      the increased residual CV risk later in life. The tolerance of an intensive
      therapeutic approach should remain a concern in elderly patients and in patients
      with established CV disease.

PMID- 29203044
TI  - [New international guidelines for curative treatment and prophylaxis for venous
      thromboembolism (VTE) in cancer patients and the dedicated smartphone
      application].
AB  - Venous thromboembolism (VTE) is a frequent and serious complication in cancer
      patients, and the second leading cause of death in this setting. Cancer patients
      are also more likely to present recurrent VTE and major bleeding while taking
      anticoagulants. Management of VTE in these patients is always challenging and
      remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis
      and Cancer (ITAC-CME) released international guidelines for the treatment and
      prophylaxis of VTE and central venous catheter-associated thrombosis, based on a
      systematic review of the literature ranked according to the Grading of
      Recommendations Assessment, Development, and Evaluation scale. An update of these
      ITAC-CME consensus guidelines, including the use of direct oral anticoagulants,
      was recently published. In this review, we summarize these updated guidelines.
      Better adherence to the international guidelines, involving an adequate
      educational and active implementation strategies, will substantially decrease the
      burden of VTE and allow to increase survival in cancer patients.

PMID- 29203045
TI  - Anaphylactic shock with an ultrasound contrast agent.
AB  - Echo contrast agents, such as SonoVue(r), (Bracco, Milan, Italy) are often used
      to enhance diagnosis. Although their use is safe, some rare side effects could be
      severe or even fatal. We are reporting a case of severe systemic allergic
      reaction after infusion of SonoVue(r). After a brief review of the literature,
      the aim of this paper is to draw attention to this risk and recall the safety
      instructions coming with the use of ultrasound contrast agents.

PMID- 29203046
TI  - [Post-traumatic carotido-jugular fistula: Case report and review of the
      literature].
AB  - The neck, being not protected by skeleton, is vulnerable to external trauma and
      injury which can involve blood vessels, muscles, nerves, and trachea. Carotid
      injuries can be potentially life-threatening by hemorrhage and stroke. We present
      a case of a 26-year-old manual worker who presented a neck injury caused by a
      metallic projectile. The injury involved the right common carotid artery with an
      internal jugular vein fistula, and tracheal damage. The patient was managed with
      surgical repair of the tracheal lesion, reconstruction of the carotid section
      using a PTFE graft bypass, and ligation of the internal jugular vein. In the
      immediate postoperative period, the patient presented with no neurological
      deficits, but he did develop a pulmonary infection that resolved with antibiotic
      therapy. The follow-up is now 3months. The patient is doing well without any
      neurological disorder.

PMID- 29203047
TI  - [Fibromuscular dysplasia exposes to early natural impregnation with
      progesterone].

PMID- 29203048
TI  - A Review of the Management of Loss of Pregnancy in the Emergency Department.
AB  - INTRODUCTION: Women frequently seek ED care for complications in early pregnancy,
      including loss of pregnancy. This review evaluates the current literature and
      discusses the care of patients experiencing loss of pregnancy in the emergency
      department. METHODS: A review of pertinent studies identified through multiple
      database searches was conducted to determine the existing body of knowledge for
      the care of ED patients diagnosed with loss of pregnancy. Each of the studies was
      examined for inclusion criteria and a subsequent analysis of the included studies
      identified themes related to the care of the women. RESULTS: Thirty-two original
      research articles and systematic reviews published between 1990 and 2016 were
      included in the review. Eleven articles addressed recommendations for clinical
      practice, 5 reported statistics related to pregnancy outcome and clinical
      presentation, 4 discussed the use of speculum examinations, 4 discussed
      interventions to decrease ED length of stay, and 3 investigated the use of
      ultrasound in the emergency department. Only 5 of the articles reviewed discussed
      emotional support and/or experiences of women with loss of pregnancy in the
      emergency department. CONCLUSION: Although there are multiple recommendations for
      the clinical management of loss of pregnancy in the emergency department, the
      psychological and emotional support of women was addressed infrequently.
      Additional studies investigating holistic care would be beneficial for ED
      providers in the management of early loss of pregnancy.

PMID- 29203049
TI  - The Use of Clinical Cervical Spine Clearance in Trauma Patients: A Literature
      Review.
AB  - INTRODUCTION: Five million patients in America are placed in spinal
      immobilization annually, with only 1% to 2% of these patients suffering from an
      unstable cervical spine injury. Prehospital agencies are employing selective and
      limited immobilization practices, but there is concern that this practice misses
      cervical spine injuries and therefore possibly predisposes patients to worsening
      injuries. METHODS: A systematic review was conducted that examined literature
      from the last 5 years that reviewed cervical spine immobilization application
      and/or clearance in alert trauma patients. RESULTS: Prehospital selective
      immobilization protocols and bedside clinical clearance examinations are becoming
      more commonplace, with few missed injuries or poor outcomes. Prehospital
      providers can evaluate patients in the field safely to assess who needs or does
      not need cervical collars; similar criteria can be used in the emergency
      department. Harm from cervical collars is increasingly documented, with concerns
      that risks exceed possible benefits. DISCUSSION: The literature suggests that
      alert trauma patients can be cleared from cervical spine immobilization safely
      through a structured algorithm in either the prehospital or ED setting. The
      evidence is primarily observational. Thus, many providers who fear missing
      cervical injuries may be reluctant to follow the recommendations despite few or
      no published cases of sudden deterioration from missed cervical spine injuries.

PMID- 29203050
TI  - Integrins: Integrating the Biology and Therapy of Cell-cell Interactions.
AB  - PURPOSE: Although the role of integrins has been described in a variety of
      diseases, these roles seem to be distinct. To date, no study has attempted to
      provide links to the various pathways by which such integrins can be involved in
      these diverse disease settings. The purpose of this review was to address this
      gap in our knowledge with the hypothesis that there is, in fact, a common pathway
      by which integrins may function. METHODS: This article provides an in-depth
      perspective on the discovery, development, and design of therapeutics that
      modulate cellular function by targeting integrin:ligand interactions by reviewing
      the literature on this subject; the review included the most recent results of
      clinical and subclinical studies. A MEDLINE search was conducted for articles
      pertaining to the various issues related to integrins, and the most relevant
      articles are discussed (ie, not only those published in journals with a higher
      impact factor). FINDINGS: It seems that the ligation of the integrins with their
      cognate ligands plays a major role in translating membrane dialogue into
      biological function. In addition, they also seem to play a major regulatory role
      that can enhance or inhibit biological function depending on the context within
      which such receptor:ligand interactions occur and the organ and tissues at which
      interactions occurs and is manipulated. Those studies that used statistical
      analyses have been included where appropriate. IMPLICATIONS: Our findings show
      that anti-integrin treatment has the potential to become a valid coadjuvant in
      the treatment of several diseases including cancer, inflammatory diseases, HIv
      infection and cardiovascular diseases.

PMID- 29203051
TI  - Thiamazole-Induced Agranulocytosis Leading to Abscessus Pneumonia-Rare, But
      Challenging.

PMID- 29203052
TI  - Impact of Passive Smoking on Lung Function and Asthma Severity in Children.

PMID- 29203053
TI  - Insulin-like Growth Factor 1 Mediates Adrenal Development Dysfunction in
      Offspring Rats Induced by Prenatal Food Restriction.
AB  - BACKGROUND: Our previous study demonstrated that prenatal food restriction (PFR)
      could induce the dysfunction of the hypothalamic-pituitary-adrenal axis and
      glucocorticoid-related glucose and lipid metabolic alterations in adult offspring
      rats. AIM OF THE STUDY: To investigate the intrauterine programming mechanism of
      adrenal dysfunction in the PFR offspring rats. METHODS: From gestational days
      (GDs) 11-20, pregnant Wistar rats were fed a restricted diet (50% of the daily
      food intake of control rats, 60 g/kg.d). Some were executed at GD20, while the
      others survived to full-term delivery; all pups were fed a high-fat diet (HFD)
      after weaning. The serum corticosterone concentration, expression level of
      adrenal steroidal synthetase, and insulin-like growth factor 1 (IGF1) signaling
      pathway were tested. RESULTS: We confirmed that the fetal body weight of the PFR
      group was lower than that of the control group, and the mRNA expression of
      adrenal steroidogenic acute regulatory protein, cytochrome P450 cholesterol side
      chain cleavage, 3beta-hydroxysteroid dehydrogenase, and steroid 11beta
      hydroxylase (P450c11) were decreased in the PFR fetal rats. The maternal and
      fetal serum corticosterone levels were significantly increased in the PFR groups.
      Furthermore, the expression of the adrenal IGF1 signaling pathway (including
      IGF1, IGF1R, and Akt1) was suppressed. However, after a post-weaning HFD, the
      body weight gain rates and serum corticosterone levels were elevated, and the
      expression of adrenal steroid 21-hydroxylase and P450c11, as well as the IGF1
      signaling pathway, were significantly increased in the PFR group. CONCLUSIONS:
      These results showed that a higher level of circulation corticosterone by PFR in
      utero inhibited adrenal IGF1 signaling and steroidogenesis, whereas post-weaning
      HFD induced adrenal steroidogenesis by an enhanced IGF1 signaling.

PMID- 29203054
TI  - On the Search to Elucidate the Role of Microbiota in the Genesis of Cancer: The
      Cases of Gastrointestinal and Cervical Cancer.
AB  - The microbiota that inhabits the human body plays an important role in health and
      disease, by their fundamental role in food digestion, training of the immune
      system or protection against pathogen colonization. However, when the equilibrium
      with its host is altered, some diseases like cancer might be promoted. In this
      review we describe the information collected in recent studies between the
      microbiota and its association with cancer. We conducted the review of the
      relation of microbiome and cancer etiology focusing on the gastrointestinal and
      cervical cancer. The MEDLINE database was used for the search. The
      gastrointestinal tract harbours a diverse and site specific microbiota, and
      several studies have demonstrated that perturbation of these microbial
      communities might be associated with different types of cancer. In particular,
      alteration of the colorectal, gastric and oesophageal microbiota have been
      reported associated with cancer development. Likewise, cervical microbiome
      studies suggest that some members of the cervical microbiota are possible
      modifiers of the cytokine profile of the cervical microenvironment during the
      development of cervical lesions and cervical cancer. Larger prospective studies
      are needed to examine whether microbiome dysbiosis could cause cancer, and to
      evaluate the utility of microbiome profiles as biomarkers for prevention and
      early diagnosis. This is an important area of research if we consider that
      microbiota may be a modifiable factor by the use of pre- and probiotics, in order
      to prevent cancer evolution or even to potentiate cancer treatment.

PMID- 29203055
TI  - Does this robot have a mind? Schizophrenia patients' mind perception toward
      humanoid robots.

PMID- 29203056
TI  - Immunohistochemistry as confirmatory test for current Helicobacter pylori
      infection in patients treated with proton pump inhibitors.

PMID- 29203057
TI  - Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status
      epilepticus revealing autoimmune encephalitis due to GABAAR antibodies.
AB  - BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) has been
      described as an epileptic encephalopathy of unknown etiology affecting previously
      healthy children following febrile illness. Despite large investigations on
      autoimmune pathogenesis no membrane antibodies has been associated since now.
      CASE STUDY: We report a 13 years-old girl with negative history for neurological
      or autoimmune disease that developed at the sixth day of high fever a super
      refractory status epilepticus. All investigations, including the most common
      antibodies related to immune-mediated encephalitis were negative. Seizures
      continued despite several therapeutic trials with anesthetics (midazolam,
      propofol) and antiepileptic agents as well as i.v. immunoglobulins but responded,
      at day 10 from the onset, to ketamine and high dose i.v. steroids. Due the high
      suspicion of autoimmune encephalitis we tested patient's CSF and plasma on mouse
      brain with positive response. We subsequently detected a high titre of GABAAR
      antibodies. After the resolution of the status epilepticus the patient achieved
      complete recovery of neurological functions. CONCLUSION: this is the first
      reported case of a FIRES-like condition due to autoimmune encephalitis mediated
      by GABAAR antibodies. Our case suggests that GABAAR antibodies should be
      investigated FIRES.

PMID- 29203058
TI  - Potential impact of the herbicide 2,4-dichlorophenoxyacetic acid on human and
      ecosystems.
AB  - The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is applied directly to
      aquatic and conventional farming systems to control weeds, and is among the most
      widely distributed pollutants in the environment. Non-target organisms are
      exposed to 2,4-D via several ways, which could produce toxic effects depending on
      the dose, frequency of exposure, and the host factors that influence
      susceptibility and sensitivity. An increasing number of experimental evidences
      have shown concerns about its presence/detection in the environment, because
      several investigations have pointed out its potential lethal effects on non
      target organisms. In this review, we critically evaluated the environmental fate
      and behavior of 2,4-D along with its eco-toxicological effects on aquatic, plants
      and human life to provide concise assessment in the light of recently published
      reports. The findings demonstrate that 2,4-D is present in a low concentration in
      surface water of regions where its usage is high. The highest concentrations of
      2,4-D were detected in soil, air and surface water surrounded by crop fields,
      which suggest that mitigation strategies must be implanted locally to prevent the
      entry of 2,4-D into the environment. A general public may have frequent exposure
      to 2,4-D due to its wide applications at home lawns and public parks, etc.
      Various in vivo and in vitro investigations suggest that several species (or
      their organs) at different trophic levels are extremely sensitive to the 2,4-D
      exposure, which may explain variation in outcomes of reported investigations.
      However, implications for the prenatal exposure to 2,4-D remain unknown because
      2,4-D-induced toxicity thresholds in organism have only been derived from
      juveniles or adults. In near future, introduction of 2,4-D resistant crops will
      increase its use in agriculture, which may cause relatively high and potentially
      unsafe residue levels in the environment. The recent findings indicate the urgent
      need to further explore fate, accumulation and its continuous low level exposure
      impacts on the environment to generate reliable database which is key in drafting
      new regulation and policies to protect the population from further exposure.

PMID- 29203059
TI  - Increased glutamate + glutamine levels in the thalamus of patients with essential
      tremor: A preliminary proton MR spectroscopic study.
AB  - INTRODUCTION: The aim of this study was to investigate the thalamic biochemical
      profile in patients with essential tremor (ET), using proton magnetic resonance
      spectroscopy (1H-MRS), and to explore the correlations between clinical and
      biochemical data. METHODS: Sixteen patients with ET and 14 healthy controls
      participated in this study. After conventional MR imaging, single-voxel 1H-MRS
      (TR = 2000 ms; TE = 28 ms) was performed by using a PROBE-SV system implemented
      on a 3-T scanner. A voxel of 10 * 10 * 15 mm involving the ventrointermediate
      (Vim) nucleus was acquired in each thalamus of all subjects. Peak areas of N
      acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine + phosphocreatine
      (Cr), glycerophosphocholine + phosphocholine (Cho), and glutamate + glutamine
      (Glx) were calculated using a version 6.3-1 K of the fitting program LCModel for
      each voxel. Comparative and correlation analyses were performed on the NAA, Cr,
      Cho, and Glx concentrations, as well as on the values of the NAA/Cr, a neural
      density marker, Cho/Cr, a membrane marker, and Glx/Cr, an intracellular
      neurotransmitter marker. RESULTS: Patients with ET showed a significant increase
      in Glx concentration and Glx/Cr ratio values in both thalami, compared to healthy
      controls, whereas no difference inter-group was found for the other metabolites
      and NAA/Cr and Cho/Cr ratio values. Of note, the tremor severity was positively
      related to increased Glx concentrations and Glx/Cr ratio values in ET group.
      CONCLUSIONS: Our study shows that 1H-MRS can highlight in vivo metabolic
      abnormalities in the thalami of ET patients, supporting the evidence that the
      increase of thalamic glutamatergic transmission can play a role in developing of
      tremor in ET.

PMID- 29203060
TI  - Prevalence of metabolic syndrome in Middle-East countries: Meta-analysis of cross
      sectional studies.
AB  - OBJECTIVE: Metabolic syndrome is an important metabolic disorder which impose
      noticeable burden on health system. We aimed to review and imply the prevalence
      of it in Middle-East countries. METHODS: present study was a systematic review to
      present overview about metabolic disorder in Middle East. Electronic literature
      search of Medline database and Google scholar were done for English-language
      articles without time filtering, as well as for population-based or national
      studies of the prevalence of metabolic syndrome. The fallowing search terms were
      used simultaneously: prevalence of "metabolic syndrome" and "national study",
      "prevalence of metabolic syndrome in Middle East", "prevalence of metabolic
      syndrome" and "name of country", "metabolic syndrome &name of country".
      Additionally, relevant articles in bibliography were searched. Analysis of data
      was carried out in STATA version 11.0. RESULTS: out of 456 studies in first-step
      searching (selecting by title) 59 studies were recruited and reviewed. Prevalence
      of metabolic syndrome fluctuated by country and time of study. This amount was
      2.2-44% in Turkish, 16-41% in Saudi-Arabia, 14-63 in Pakistan, 26-33 in Qatar, 9
      36 in Kuwait, 22-50 in Emirate, 6-42 in Iran, and up to 23 in Yemen. Pooled
      estimate was 25%. Attributable risk for cardiovascular disease, coronary heart
      disease, and stroke was 15.87, 11.7, and 16.23, respectively. CONCLUSION: The
      prevalence rate of metabolic syndrome is high and it is noticeable cause for
      stroke, coronary heart disease, and cardiovascular disease.

PMID- 29203061
TI  - Answer to the article: "Serratia marcescens bacteraemia outbreak in
      hemodialysis". Comment on "Serratia marcescens bacteraemia outbreak in
      haemodialysis patients with tunnelled catheters due to colonisation of antiseptic
      solution. Experience at 4 hospitals".

PMID- 29203062
TI  - Serratia marcescens bacteraemia outbreak in hemodialysis. Comment on "Serratia
      marcescens bacteraemia outbreak in haemodialysis patients with tunnelled
      catheters due to colonisation of antiseptic solution. Experience from 4
      hospitals".

PMID- 29203063
TI  - Complex regional pain syndrome associated with erythropoietin therapy.

PMID- 29203064
TI  - Use of diazoxide in hypoglycemia with hyperinsulinemia in hemodialysis.

PMID- 29203065
TI  - [Severe ipilimumab-induced ulcerative colitis remitting after infliximab therapy
      and secondary switching with pembrolizumab].

PMID- 29203066
TI  - [The sural medial perforator flap: Anatomical bases, surgical technique and
      indications in head and neck reconstruction].
AB  - INTRODUCTION: The medial sural artery perforator (MSAP) flap is defined as a thin
      cutaneo-adipose perforator flap harvested on the medial aspect of the leg. The
      aims of this study were to describe the anatomical basis as well as the surgical
      technique and discuss the indications in head and neck reconstructive surgery.
      MATERIAL AND METHODS: We harvested 10 MSAP flap on 5 fresh cadavers. For each
      case, the number and the location of the perforators were recorded. For each
      flap, the length of pedicle, the diameter of source vessels and the thickness of
      the flap were studied. Finally, we performed a clinical application of a MSAP
      flap. RESULTS: A total of 23 perforators with a diameter superior than 1mm were
      dissected on 10 legs. The medial sural artery provided between 1 and 4
      musculocutaneous perforators. Perforators were located in average at 10.3cm+/-2cm
      from the popliteal fossa and at 3.6cm+/-1cm from the median line of the calf. The
      mean pedicle length was 12.1cm+/-2.5cm. At its origin, the source artery diameter
      was 1.8mm+/-0.25mm and source veins diameters were 2.45mm+/-0.9mm in average.
      There was no complication in our clinical application. DISCUSSION: This study
      confirms the reliability of previous anatomical descriptions of the medial sural
      artery perforator flap. This flap was reported as thin and particularly adapted
      for oral cavity reconstruction and for facial or limb resurfacing. Sequelae might
      be reduced as compared to those of the radial forearm flap with comparable
      results.

PMID- 29203067
TI  - Personalized Prediction of Glaucoma Progression Under Different Target
      Intraocular Pressure Levels Using Filtered Forecasting Methods.
AB  - PURPOSE: To generate personalized forecasts of how patients with open-angle
      glaucoma (OAG) experience disease progression at different intraocular pressure
      (IOP) levels to aid clinicians with setting personalized target IOPs. DESIGN:
      Secondary analyses using longitudinal data from 2 randomized controlled trials.
      PARTICIPANTS: Participants with moderate or advanced OAG from the Collaborative
      Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention
      Study (AGIS). METHODS: By using perimetric and tonometric data from trial
      participants, we developed and validated Kalman Filter (KF) models for fast-,
      slow-, and nonprogressing patients with OAG. The KF can generate personalized and
      dynamically updated forecasts of OAG progression under different target IOP
      levels. For each participant, we determined how mean deviation (MD) would change
      if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or
      24 mmHg) over the next 5 years. We also model and predict changes to MD over the
      same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the
      level attained in the trials. MAIN OUTCOME MEASURES: Personalized estimates of
      the change in MD under different target IOP levels. RESULTS: A total of 571
      participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a
      mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on
      average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under
      target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on
      average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same
      target IOPs and time frame. When using our tool to quantify the OAG progression
      dynamics for all 571 patients, we found no statistically significant differences
      over 5 years between progression for black versus white, male versus female, and
      CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all).
      CONCLUSIONS: To our knowledge, this is the first clinical decision-making tool
      that generates personalized forecasts of the trajectory of OAG progression at
      different target IOP levels. This approach can help clinicians determine
      appropriate, personalized target IOPs for patients with OAG.

PMID- 29203068
TI  - Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing
      Frequencies for Treatment of Keratoconus and Corneal Ectasia.
AB  - PURPOSE: To investigate whether the riboflavin dosing frequency affects corneal
      cross-linking efficacy or safety, given that isotonic riboflavin solution is
      viscous and each installation coats the corneal surface with a film that absorbs
      some of the incident ultraviolet A light. DESIGN: Prospective, randomized, single
      center equivalence trial. PARTICIPANTS: Patients with progressive keratoconus or
      ectasia after refractive surgery (n = 510). METHODS: One eye per patient was
      prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with
      standard corneal cross-linking (epithelial removal and 30-minute irradiation with
      3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable
      representation of keratoconus and ectasia after refractive surgery in the 2
      treatment arms. Treatment equivalence was assessed using the 2 one-sided test.
      Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the
      safety analysis. MAIN OUTCOME MEASURES: The primary hypothesis was equivalent
      change in the topography-derived maximum keratometry value from baseline to 6
      months with 2-minute vs. 5-minute dosing. A +/-0.75-diopter margin of equivalence
      for the treatment difference between dosing regimens was considered clinically
      relevant. Adverse events and changes from baseline to 6 months in corrected
      distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum
      corneal thickness were assessed. RESULTS: The mean reduction in maximum
      keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin
      dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90%
      confidence interval for treatment difference, -0.23 to 0.66; per-protocol
      population). With both dosing intervals, the mean improvement in CDVA was 0.07
      logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the
      635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost
      2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1
      (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent
      epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS: The 2
      riboflavin dosing regimens produced equivalent reduction in the maximum
      keratometry value, with a favorable safety profile.

PMID- 29203069
TI  - Thinking critically about health and human-animal relations: Therapeutic affect
      within spaces of care farming.
AB  - This article draws on a more-than-representational approach to reconsider how
      geographers engage with ideas of 'health'. Health can be understood as the
      constant reshaping of an individual's capacity to affect and be affected, the way
      in which a body's powers to act are dynamically augmented or diminished by
      different affective relations. The article also addresses calls for health
      geography to engage with the more-than-human. The article mobilises a qualitative
      study of 'care farming' within England and Wales to highlight the generative
      potential of human-animal relations in (re)shaping the diverse affective
      relations gathered together to produce new bodily capacities. The article
      demonstrates how animal presence and agency can break down barriers, allowing
      people to navigate and negotiate adverse contexts and access support in a manner
      and space in which they feel comfortable. Additionally, human-animal relations
      are shown to produce affective experiences that act to re-place identities,
      understandings, and ways of 'being-with' the world that can enact what different
      actants may become. Human-animal relations matter for health.

PMID- 29203071
TI  - MiStent: just another example of non-inferiority?

PMID- 29203070
TI  - A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an
      everolimus-eluting durable polymer stent (Xience) after percutaneous coronary
      intervention (DESSOLVE III): a randomised, single-blind, multicentre, non
      inferiority, phase 3 trial.
AB  - BACKGROUND: MiStent is a drug-eluting stent with a fully absorbable polymer
      coating containing and embedding a microcrystalline form of sirolimus into the
      vessel wall. It was developed to overcome the limitation of current durable
      polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of
      MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting
      stents has not been investigated in a large randomised trial in an all-comer
      population. METHODS: We did a randomised, single-blind, multicentre, phase 3
      study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland.
      Eligible participants were any patients aged at least 18 years who underwent
      percutaneous coronary intervention in a lesion and had a reference vessel
      diameter of 2.50-3.75 mm. We randomly assigned patients (1:1) to implantation of
      either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus
      eluting durable polymer stent (Xience). Randomisation was done by local
      investigators via web-based software with random blocks according to centre. The
      primary endpoint was a non-inferiority comparison of a device-oriented composite
      endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically
      indicated target lesion revascularisation-between the groups at 12 months after
      the procedure assessed by intention-to-treat. A margin of 4.0% was defined for
      non-inferiority of the MiStent group compared with the Xience group. All
      participants were included in the safety analyses. This trial is registered with
      ClinicalTrials.gov, number NCT02385279. FINDINGS: Between March 20, and Dec 3,
      2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with
      1037 lesions were assigned to MiStent, of whom 697 received the index procedure,
      and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received
      the index procedure. At 12 months, the primary endpoint had occurred in 40
      patients (5.8%) in the sirolimus-eluting stent group and in 45 patients (6.5%) in
      the everolimus-eluting stent group (absolute difference -0.8% [95% CI -3.3 to
      1.8], pnon-inferiority=0.0001). Procedural complications occurred in 12 patients
      (1.7%) in the sirolimus-eluting stent group and ten patients (1.4%) in the
      everolimus-eluting stent group; no clinical adverse events could be attributed to
      these dislodgements through a minimum of 12 months of follow-up. The rate of
      stent thrombosis, a safety indicator, did not differ between groups and was low
      in both treatment groups. INTERPRETATION: The sirolimus-eluting bioabsorbable
      polymer stent was non-inferior to the everolimus-eluting durable polymer stent
      for a device-oriented composite clinical endpoint at 12 months in an all-comer
      population. MiStent seems a reasonable alternative to other stents in clinical
      practice. FUNDING: The European Cardiovascular Research Institute, Micell
      Technologies (Durham, NC, USA), and Stentys (Paris, France).

PMID- 29203072
TI  - Practical and theoretical considerations on the fracture toughness testing of
      dental restorative materials.
AB  - BACKGROUND: An important tool in materials research, development and
      characterization regarding mechanical performance is the testing of fracture
      toughness. A high level of accuracy in executing this sort of test is necessary,
      with strict requirements given in extensive testing standard documents.
      Proficiency in quality specimen fabrication and test requires practice and a
      solid theoretical background, oftentimes overlooked in the dental community.
      AIMS: In this review we go through some fundamentals of the fracture mechanics
      concepts that are relevant to the understanding of fracture toughness testing,
      and draw attention to critical aspects of practical nature that must be fulfilled
      for validity and accuracy in results. We describe our experience with some
      testing methodologies for CAD/CAM materials and discuss advantages and
      shortcomings of different tests in terms of errors in testing the applicability
      of the concept of fracture toughness as a single-value material-specific
      property.

PMID- 29203073
TI  - Effect of the Glide Path Establishment on the Torque Generation to the Files
      during Instrumentation: An In Vitro Measurement.
AB  - INTRODUCTION: The purpose of this study was to compare in vitro torque generation
      during instrumentation with or without glide path establishment. METHODS: Endo
      training resin blocks with J-shaped canals were randomly divided into 2 groups
      according to glide path establishment (with or without) and subdivided into 2
      subgroups with shaping instruments (WaveOne [Dentsply Maillefer, Ballaigues,
      Switzerland] or WaveOne Gold [Dentsply Maillefer]) (n = 15). For the glide path
      established group, the glide path was prepared using ProGlider (Dentsply
      Maillefer). During the instrumentation with WaveOne or WaveOne Gold, in vitro
      torque was measured. The acquired data were analyzed with software. The maximum
      torque and total torque (the sum of the generated torque) were calculated. The
      data were statistically evaluated using 2-way analysis of variance and the Duncan
      post hoc comparison to examine any correlation of torque generation with glide
      path establishment and nickel-titanium instruments. The significance level was
      set at 95%. RESULTS: The generated total torque by WaveOne Gold was significantly
      reduced by glide path establishment (P < .05), whereas glide path establishment
      did not induce significant changes in the maximum torque for both file systems.
      WaveOne Gold with a glide path showed the lowest total torque generation among
      all groups (P < .05). WaveOne generated a higher maximum torque than WaveOne Gold
      regardless of the establishment of a glide path (P < .05). CONCLUSIONS: Under the
      limitations of this study, glide path establishment and the mechanical property
      of instruments have a significant influence on torque generation. It is
      recommended to create the glide path and use a flexible file to reduce torque
      generation and, consequently, the risk of file fracture and root dentin damage.

PMID- 29203074
TI  - Microscopic biliary and perineural invasion and clinical outcome after
      neoadjuvant bevacizumab-based chemotherapy and liver resection in patients with
      colorectal liver metastases.
AB  - BACKGROUND: The value of microscopic biliary and perineural invasion as
      prognostic biomarkers in patients with resectable colorectal liver metastases
      (CLM) who undergo neoadjuvant chemotherapy and liver resection is still unclear.
      This retrospective study was performed to elucidate this issue. METHODS:
      Histologic slides of resected CLM of patients who underwent neoadjuvant
      bevacizumab-based chemotherapy and liver resection were investigated with respect
      to biliary and perineural invasion. Presence of invasion was correlated with
      radiologic and histologic response, recurrence-free survival (RFS) and overall
      survival (OS). RESULTS: One hundred forty-one patients were enrolled. There was a
      significant association between biliary and perineural invasion, respectively (P
      = 0.001). Moreover, both biliary and perineural invasion were associated with
      bilobar metastatic spread and higher number of metastases, while perineural
      invasion was also associated with a higher Fong score. No significant association
      was found with response. In univariable analysis, biliary and perineural invasion
      were associated with shorter RFS (median 10.1 vs. 13.5 months, HR 2.09, P = 0.010
      and 7.6 vs. 14.0, HR 2.23, P = 0.001, respectively). Biliary invasion was also
      associated with shorter OS (median 32.8 months vs. not reached, HR 2.78, P =
      0.010), however these results did not remain significant in multivariable
      analysis. CONCLUSIONS: In patients with resectable colorectal liver metastases
      undergoing neoadjuvant bevacizumab-based chemotherapy and liver resection,
      biliary and perineural invasion are associated with higher tumor load but may not
      be prognostic biomarkers.

PMID- 29203075
TI  - The role of ultrasonography of the axilla and fine-needle aspiration cytology in
      breast cancer patients in the era of neo-adjuvant chemotherapy and axillary
      radiation; prevention of futile sentinel node procedures revisited.

PMID- 29203076
TI  - The decay of engineered wood products and paper excavated from landfills in
      Australia.
AB  - Large volumes of engineered wood products (EWPs) and paper are routinely placed
      in landfills in Australia, where they are assumed to decay. However, the extent
      of decay for EWPs is not well-known. This study reports carbon loss from EWPs and
      paper buried in landfills in Sydney, Brisbane and Cairns in Australia, located in
      temperate, subtropical and tropical climates, respectively. The influence of pulp
      type (mechanical and chemical) and landfill type (municipal solid waste - MSW and
      construction and demolition - C&D) on decay levels were investigated. Carbon loss
      for EWPs ranged from 0.6 to 9.0%; though there is some uncertainty in these
      values due to limitations associated with sourcing appropriate controls. Carbon
      loss for paper products ranged from 0 to 58.9%. Papers produced from
      predominantly mechanical pulps generally had lower levels of decay than those
      produced via chemical or partly chemical processes. Typically, decay levels for
      paper products were highest for the tropical Cairns landfill, suggesting that
      climate may be a significant factor to be considered when estimating emissions
      from paper in landfills. For EWPs, regardless of the landfill type and climate,
      carbon losses were low, confirming results from previous laboratory studies.
      Lower carbon losses were observed for EWP and paper excavated from the Sydney C&D
      landfill, compared with the Sydney MSW landfill, confirming the hypothesis that
      conditions in C&D landfills are less favourable for decay. These results have
      implications for greenhouse gas inventory estimations, as carbon losses for EWPs
      were lower than the commonly assumed values of 23% (US EPA) and 50%
      (Intergovernmental Panel on Climate Change). For paper types, we suggest that
      separate decay factors should be used for papers dominated by mechanical pulp and
      those produced from mostly chemical pulps, and also for papers buried in tropical
      or more temperate climates.

PMID- 29203077
TI  - Waste wood as bioenergy feedstock. Climate change impacts and related emission
      uncertainties from waste wood based energy systems in the UK.
AB  - Considering the urgent need to shift to low carbon energy carriers, waste wood
      resources could provide an alternative energy feedstock and at the same time
      reduce emissions from landfill. This research examines the climate change impacts
      and related emission uncertainties of waste wood based energy. For this,
      different grades of waste wood and energy application have been investigated
      using lifecycle assessment. Sensitivity analysis has then been applied for supply
      chain processes and feedstock properties for the main emission contributing
      categories: transport, processing, pelletizing, urea resin fraction and related
      N2O formation. The results show, depending on the waste wood grade, the
      conversion option, scale and the related reference case, that emission reductions
      of up to 91% are possible for non-treated wood waste. Compared to this, energy
      from treated wood waste with low contamination can achieve up to 83% emission
      savings, similar to untreated waste wood pellets, but in some cases emissions
      from waste wood based energy can exceed the ones of the fossil fuel reference -
      in the worst case by 126%. Emission reductions from highly contaminated
      feedstocks are largest when replacing electricity from large-scale coal and
      landfill. The highest emission uncertainties are related to the wood's resin
      fraction and N2O formation during combustion and, pelletizing. Comparing wood
      processing with diesel and electricity powered equipment also generated high
      variations in the results, while emission variations related to transport are
      relatively small. Using treated waste wood as a bioenergy feedstock can be a
      valid option to reduce emissions from energy production but this is only
      realisable if coal and landfill gas are replaced. To achieve meaningful emission
      reduction in line with national and international climate change targets, pre
      treatment of waste wood would be required to reduce components that form N2O
      during the energy conversion.

PMID- 29203078
TI  - Response to Arteaga et al.

PMID- 29203079
TI  - Residual pressure gradient across the implanted stent: An important factor of
      post-PCI physiological results.
AB  - BACKGROUND: Instantaneous wave-free ratio (iFR) has the potential to improve the
      accuracy of the prediction of the physiological result of percutaneous coronary
      intervention (PCI). The aim of this study was to evaluate the accuracy of iFR to
      predict the final physiological results following PCI, and investigate the
      factors for failed prediction. METHODS: In 73 lesions, iFR pullback recordings
      were measured and comparisons were made between the predicted improvement
      following PCI and the observed result. RESULTS: iFR predicted-observed difference
      was 0.036+/-0.037. Multivariate analysis showed residual iFR pressure gradient
      across the implanted stent (odds ratio, 2.329; 95% confidence interval, 1.408
      3.853; p=0.0010) as an independent risk factor for error in iFR prediction.
      CONCLUSIONS: iFR predicted-observed difference was 0.036+/-0.037. Residual in
      stent iFR pressure gradient following PCI is the only independent risk factor for
      failed prediction.

PMID- 29203080
TI  - Diastolic wall strain is associated with incident heart failure in African
      Americans: Insights from the atherosclerosis risk in communities study.
AB  - BACKGROUND: Increased left ventricular (LV) myocardial stiffness may be
      associated with impaired LV hemodynamics and incident heart failure (HF).
      However, an indicator that estimates LV myocardial stiffness easily and non
      invasively is lacking. The purpose of this study was to determine whether
      diastolic wall strain (DWS), an echocardiographic estimator of LV myocardial
      stiffness, is associated with incident HF in a middle-aged community-based cohort
      of African Americans. METHODS AND RESULTS: We investigated associations between
      DWS and incident HF among 1528 African Americans (mean age 58.5 years, 66% women)
      with preserved LV ejection fraction (EF >=50%) and without a history of
      cardiovascular disease in the Atherosclerosis Risk in Communities Study.
      Participants with the smallest DWS quintile (more LV myocardial stiffness) had a
      higher LV mass index, higher relative wall thickness, and lower arterial
      compliance than those in the larger four DWS quintiles (p<0.01 for all). Over a
      mean follow-up of 15.6 years, there were 251 incident HF events (incidence rate:
      10.9 per 1000 person-years). After adjustment for traditional risk factors and
      incident coronary artery disease, both continuous and categorical DWS were
      independently associated with incident HF (HR 1.21, 95%CI 1.04-1.41 for 0.1
      decrease in continuous DWS, p=0.014, HR 1.40, 95%CI 1.05-1.87 for the smallest
      DWS quintile vs other combined quintiles, p=0.022). CONCLUSIONS: DWS was
      independently associated with an increased risk of incident HF in a community
      based cohort of African Americans. DWS could be used as a qualitative estimator
      of LV myocardial stiffness.

PMID- 29203081
TI  - Semi-automated QRS score as a predictor of survival in CRT treated patients with
      strict left bundle branch block.
AB  - BACKGROUND: Cardiac Resynchronization Therapy (CRT) is widely used for treating
      selected heart failure patients, but patients with myocardial scar respond worse
      to treatment. The Selvester QRS scoring system estimates myocardial scar burden
      using 12-lead ECG. This study's objective was to investigate the scores
      correlation to mortality in a CRT population. METHODS AND RESULTS: Data on
      consecutive CRT patients was collected. 401 patients with LBBB and available ECG
      data were included in the study. QuAReSS software was used to perform Selvester
      scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The
      endpoint was death or heart transplant; outcome was analyzed using Cox
      proportional hazards models. A Selvester score >8 was significantly associated
      with higher risk of the combined endpoint (HR 1.59, p=.014, CI 1.09-2.3).
      CONCLUSION: Higher Selvester scores correlate to mortality in CRT patients with
      strict LBBB and might be of value in prognosticating survival.

PMID- 29203082
TI  - Training tomorrow's doctors to explain 'medically unexplained' physical symptoms:
      An examination of UK medical educators' views of barriers and solutions.
AB  - OBJECTIVE: Co-occuring physical symptoms, unexplained by organic pathology (known
      as Functional Syndromes, FS), are common and disabling presentations. However, FS
      is absent or inconsistently taught within undergraduate medical training. This
      study investigates the reasons for this and identifies potential solutions to
      improved implementation. METHODS: Twenty-eight medical educators from thirteen
      different UK medical schools participated in semi-structured interviews. Thematic
      analysis proceeded iteratively, and in parallel with data production. RESULTS:
      Barriers to implementing FS training are beliefs about the complexity of FS,
      tutors' negative attitudes towards FS, and FS being perceived as a low priority
      for the curriculum. In parallel participants recognised FS as ubiquitous within
      medical practice and erroneously assumed it must be taught by someone. They
      recommended that students should learn about FS through managed exposure, but
      only if tutors' negative attitudes and behaviour are also addressed. CONCLUSION:
      Negative attitudes towards FS by educators prevents designing and delivering
      effective education on this common medical presentation. Whilst there is
      recognition of the need to implement FS training, recommendations are
      multifaceted. PRACTICE IMPLICATIONS: Increased liaison between students, patients
      and educators is necessary to develop more informed and effective teaching
      methods for trainee doctors about FS and in order to minimise the impact of the
      hidden curriculum.

PMID- 29203083
TI  - Effect of different formats for information on side effects regarding medicine
      users' understanding: A randomized controlled trial.
AB  - OBJECTIVE: The objective of this randomized controlled trial was to evaluate the
      efficacy of presenting information on the risks of side effects from a medicine,
      presented in different formats. METHODS: A randomized, parallel-group, single
      center controlled trial was conducted among adult users of a training pharmacy.
      The information was categorized into the following groups: verbal
      descriptors+percentage range, percentage range and absolute percentage. The main
      outcomes were gist understanding and verbatim understanding, classified either as
      adequate or inadequate. The analyses were performed using ANOVA and Pearson's chi
      square test. RESULTS: A total of 393 participants were recruited from June to
      October 2015. Adequate levels of gist understanding and verbatim understanding
      were respectively 65.6% and 53.9% for the verbal descriptors+percentage range
      (n=128), 63.4% and 44.3% for percentage range (n=131), and 62.3% and 48.5% for
      absolute percentage (n=131), with no statistically significant difference between
      the groups (p=0.852 and p=0.299, respectively). CONCLUSION: The understanding of
      the information was similar in all three formats, but the percentages of adequate
      understanding were low. PRACTICAL IMPLICATIONS: The percentage of inadequate
      understanding demonstrated in this study indicates that alternative formats for
      reporting adverse reactions need to be evaluated.

PMID- 29203085
TI  - Large-Scale Gradients in Human Cortical Organization.
AB  - Recent advances in mapping cortical areas in the human brain provide a basis for
      investigating the significance of their spatial arrangement. Here we describe a
      dominant gradient in cortical features that spans between sensorimotor and
      transmodal areas. We propose that this gradient constitutes a core organizing
      axis of the human cerebral cortex, and describe an intrinsic coordinate system on
      its basis. Studying the cortex with respect to these intrinsic dimensions can
      inform our understanding of how the spectrum of cortical function emerges from
      structural constraints.

PMID- 29203084
TI  - The impact of genetic counselors' use of facilitative strategies on cognitive and
      emotional processing of genetic risk disclosure for Alzheimer's disease.
AB  - OBJECTIVES: To determine the impact of genetic counselor (GC) communication on
      cognitive and emotional processing of Alzheimer's disease (AD) risk information
      during discussions with patients with clinical diagnoses of mild cognitive
      impairment and their companion. METHODS: 79 recordings and transcripts of AD risk
      disclosure sessions collected as part of the fourth REVEAL Trial were coded using
      the Roter Interaction Analysis System (RIAS) and the Linguistic Inquiry Word
      Count (LIWC). Multilevel analyses were used to determine the association between
      GCs' use of communication facilitation strategies and patient and companion use
      of words indicative of cognitive and emotional processing. RESULTS: GC used
      somewhat more cognitive (14%) than emotional (10%) facilitation strategies. Both
      patients and companions used more words indicative of cognitive (18% and 17%)
      than emotional (6% and 5%) processing. GC use of facilitative strategies and
      patient and companion use of cognitive and emotional processing words were
      significantly associated in both unadjusted and adjusted models (all p
      values<0.01). CONCLUSIONS: GCs' use of facilitative strategies assist in
      cognitive and emotional processing in a way that may be linked to therapeutic
      benefit. PRACTICE IMPLICATIONS: These findings highlight mechanisms through which
      GCs may assist patients and companions to better understand and cope with risk
      information.

PMID- 29203086
TI  - Editorial overview: Making evolutionary sense of everything.

PMID- 29203087
TI  - Rebuttal to the Letter to the Editor by Siamak Sabour, MEDDOS-D-17-00095.

PMID- 29203088
TI  - Ontogenetic prey size selection in snakes: predator size and functional
      limitations to handling minimum prey sizes.
AB  - As body size increases, some predators eliminate small prey from their diet
      exhibiting an ontogenetic shift toward larger prey. In contrast, some predators
      show a telescoping pattern of prey size in which both large and small prey are
      consumed with increasing predator size. To explore a functional explanation for
      the two feeding patterns, I examined feeding effort as both handling time and
      number of upper jaw movements during ingestion of fish of consistent size. I used
      a range of body sizes from two snake species that exhibit ontogenetic shifts in
      prey size (Nerodia fasciata and N. rhombifer) and a species that exhibits
      telescoping prey size with increased body size (Thamnophis proximus). For the two
      Nerodia species, individuals with small or large heads exhibited greater
      difficulty in feeding effort compared to snakes of intermediate size. However,
      for T. proximus measures of feeding effort were negatively correlated with head
      length and snout-vent length (SVL). These data indicate that ontogenetic shifters
      of prey size develop trophic morphology large enough that feeding effort
      increases for disproportionately small prey. I also compared changes in body size
      among the two diet strategies for active foraging snake species using data
      gleaned from the literature to determine if increased change in body size and
      thereby feeding morphology is observable in snakes regardless of prey type or
      foraging habitat. Of the 30 species sampled from literature, snakes that exhibit
      ontogenetic shifts in prey size have a greater magnitude of change in SVL than
      species that have telescoping prey size patterns. Based upon the results of the
      two data sets above, I conclude that ontogenetic shifts away from small prey
      occur in snakes due, in part, to growth of body size and feeding structures
      beyond what is efficient for handling small prey.

PMID- 29203089
TI  - Multivariate analysis of risk factors for postoperative wound infection following
      oral and oropharyngeal cancer surgery.
AB  - PURPOSE: The goal of this study was to identify risk factors for wound infections
      in patients with oral cancer who underwent surgical procedures. MATERIALS AND
      METHODS: This study included 195 patients who underwent surgical treatment of
      oral and oropharyngeal cancer over a 7-year period. Wound infection was defined
      as the occurrence of purulent content from the wound or as an appearance of
      exudate with signs of local infection and positive cultures taken from the wound.
      For every patient who was suspected to have a wound infection, a swab from the
      wound was taken, and microbiological analysis was performed. The patients were
      divided into 2 groups: patients with postoperative wound infections, and patients
      with postoperative wound infection. RESULTS: Wound infection was present in 155
      patients (59%). Univariate analysis indicated that the following factors were
      significantly related to the occurrence of wound infection: gender, smoking,
      tumor localization, size and stage of the tumor, type of surgery, neck
      dissection, type of reconstruction, nasogastric sonde, gastrostomy and
      tracheotomy. On multivariate analysis, statistically significant predictors of
      wound infection were gender, tumor localization and type of reconstruction.
      CONCLUSIONS: The occurrence of wound infection is high despite antibiotic
      prophylaxis. To minimize the risk of wound infection and for prompt recognition
      of risk factors, surgeons managing oral tumor patients should have a better
      understanding of the risk factors such as gender, tumor localization and type of
      reconstruction.

PMID- 29203090
TI  - Regional patterns of gray matter volume, hypometabolism, and beta-amyloid in
      groups at risk of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by the presence of beta-amyloid (Abeta)
      deposition and neurodegeneration. To seek for signs of such pathologies, we
      compared regional biomarker degrees and patterns of Abeta deposition, glucose
      hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD.
      In elderly carriers of the apolipoprotein E epsilon4 (APOE4, n = 17), patients
      with subjective cognitive decline (n = 16), and patients with mild cognitive
      impairment (n = 30), head-to-head intermodality comparisons were performed on
      cross-sectional structural magnetic resonance images as well as 18F
      fluorodeoxyglucose and 18F-florbetapir positron emission tomography scans. In
      mild cognitive impairment patients, 3 distinct biomarker patterns were recovered,
      similarly seen in AD patients: (1) in medial temporal regions, local GMV
      reduction exceeded hypometabolism, (2) in temporoparietal regions, hypometabolism
      predominated over GMV reduction, and (3) in frontal regions, Abeta deposition
      exceeded GMV reduction and hypometabolism. In subjective cognitive decline
      patients, only pattern 1 was detected, while APOE4 carriers demonstrated only
      pattern 3. Our findings highlight that regional AD-like biomarker patterns may
      vary across different at-risk populations, potentially reflecting differential
      mediators of these risks.

PMID- 29203091
TI  - Re-irradiation of Vertebral Body Metastases: Treatment in the Radiosurgery Era.
AB  - Vertebral bodies remain one of the most common sites of metastases. In cases
      where surgical intervention is not indicated or appropriate, conventional
      external radiation therapy (cEBRT) has been the standard treatment modality.
      Unfortunately, cEBRT is typically limited, with low complete response and poor
      local control rates. Disappointing results with re-irradiation using cEBRT
      highlight the need for innovative salvage therapeutic strategies, such as
      stereotactic body radiotherapy. A detailed description of this complex treatment
      strategy is outlined, as is a systematic review of current literature. Although
      data are limited to single institution series, re-irradiation has consistently
      been found to be effective with respect to local control (1 year rates range from
      66 to 90%) and pain response. Importantly, the treatment is shown to be safe,
      with the crude rate of radiation myelopathy <1% and a rate of vertebral
      compression fracture of 12%. As further research and technologic advances
      continue to refine therapy, stereotactic body radiotherapy is now a recommended
      option for the treatment of previously irradiated vertebral body metastases.

PMID- 29203092
TI  - Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator
      activated receptor alpha modulator, in patients with dyslipidemia: Results from a
      24-week, randomized, double blind, active-controlled, phase 3 trial.
AB  - BACKGROUND: To overcome the concerns associated with the use of fibrates,
      pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor
      modulator, was developed. In a previous phase 2 trial, we showed excellent
      efficacy and safety of pemafibrate in patients with dyslipidemia. OBJECTIVE: The
      objective of the study was to evaluate the efficacy and safety of pemafibrate
      over 24 weeks in adults with dyslipidemia in comparison with fenofibrate.
      METHODS: In this multicenter, 24-week, double-blind, clinical study, 225 patients
      with high triglyceride (TG; >=150 mg/dL [1.7 mmol/L] and <500 mg/dL [5.7 mmol/L])
      and relatively low high-density lipoprotein cholesterol (<50 mg/dL [1.3 mmol/L]
      in men or 55 mg/dL [1.4 mmol/L] in women) levels were randomized to receive
      either pemafibrate at 0.2 or 0.4 mg/d or fenofibrate 106.6 mg/d. RESULTS:
      Pemafibrate 0.2, 0.4 mg/d and fenofibrate significantly reduced TG levels from
      baseline by -46.2%, -45.9%, and -39.7%, respectively. As compared with
      fenofibrate, the least squares mean differences (95% confidence intervals) in TG
      were -6.5% (-12.0, -1.1) and -6.2% (-11.6, -0.8) in pemafibrate 0.2 and 0.4 mg/d
      respectively, which showed the superiority of these doses of pemafibrate to 106.6
      mg/d of fenofibrate. The incidence rates of adverse drug reactions in pemafibrate
      groups (2.7% and 6.8%) were significantly lower than that in the fenofibrate
      group (23.7%). Pemafibrate significantly decreased alanine aminotransferase and
      gamma-glutamyltransferase levels, whereas fenofibrate increased both of them. The
      increments of serum creatinine and cystatin C were smaller in pemafibrate than
      those in fenofibrate. CONCLUSIONS: Pemafibrate was superior to fenofibrate in
      terms of serum TG-lowering effect and hepatic and renal safety.

PMID- 29203093
TI  - The growth and development of gerontological nurse leaders in policy.
AB  - BACKGROUND: The National Hartford Center of Gerontological Nursing Excellence
      (NHCGNE) Scholars/Fellows Award Program was designed to promote the growth and
      development of nurse scientists, educators, and leaders in aging. PURPOSE:
      McBride's conceptual framework of the growth and development of nurse leaders was
      used to examine the NHCGNE impact on health and aging policy work among
      scholars/fellows, including barriers, facilitators, and resources. METHODS: A
      multimethod two-phased approach included an online survey (phase I) focused on
      research and policy impact at local, state, or national level. Telephone
      interviews (phase II) were conducted to further understand the nature, depth, and
      focus of respondents' policy work. DISCUSSION: Based on our findings, we propose
      multilevel recommendations for advancing nurse scientists' capacity to be leaders
      in shaping policy. Keen research skills are influential in policy advancement but
      not sufficient to advance policy. Preparing nurse scientists with competencies in
      translating research into policy can ultimately transform health and health care
      for older adults.

PMID- 29203094
TI  - Percutaneous stent placement for malignant hilar biliary obstruction: a
      comparison between criss-cross and T-configuration techniques.
AB  - AIM: To compare the clinical effectiveness of percutaneous stent placement
      between T and criss-cross configuration techniques in patients with advanced
      malignant hilar biliary obstruction. MATERIALS AND METHODS: Between January 2009
      and December 2014, 59 patients who underwent percutaneous stent placement for
      malignant hilar obstruction were included in this retrospective study. T
      configured stent placement (T group) was performed in 33 patients and criss-cross
      configured stent placement (criss-cross group) in 26 patients. Technical and
      clinical success, complications, patient survival, and stent patency were
      compared between the two groups. RESULTS: Stent placement was technically
      successful in all patients of the two groups. Clinical success was achieved in 30
      (90.9%) patients of T group and 25 (96.9%) of criss-cross group (p=0.62). Two
      patients in the T group (6.1%) required additional stent placement for internal
      drainage of undrained sector. There were no major complications. Median survival
      was not statistically different between the two groups (128 days in the T group
      versus 183 days in the criss-cross group; p=0.33). Stent occlusion occurred in 15
      patients in the T group and seven patients in the criss-cross group. The stent
      patency of the criss-cross group (median 330 days) was longer than that of the T
      group (median 132 days; p=0.0007). CONCLUSIONS: Early clinical effectiveness is
      comparable between the two techniques; however, additional intervention is
      occasionally required for drainage of an undrained sector after T-configured
      stent placement. Stent placement with criss-cross configuration provides longer
      stent patency than T-configuration technique.

PMID- 29203095
TI  - Curved multiplanar reconstruction of CT scans for demonstration of multifocal
      metastatic lung nodules in children in a single image.

PMID- 29203096
TI  - Meningococcal disease, a clinical and epidemiological review.
AB  - Meningococcal disease is the acute infection caused by Neisseria meningitidis,
      which has humans as the only natural host. The disease is widespread around the
      globe and is known for its epidemical potential and high rates of lethality and
      morbidity. The highest number of cases of the disease is registered in the semi
      arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional
      outbreaks, epidemics and sporadic cases occurring throughout the year, especially
      in the winter. The major epidemics of the disease occurred in Brazil in the 70's
      caused by serogroups A and C. Serogroups B, C and Y represent the majority of
      cases in Europe, the Americas and Australia. However, there has been a growing
      increase in serogroup W in some areas. The pathogen transmission happens for
      respiratory route (droplets) and clinically can lead to meningitis and sepsis
      (meningococcemia). The treatment is made with antimicrobial and supportive care.
      For successful prevention, we have some measures like vaccination,
      chemoprophylaxis and droplets' precautions. In this review, we have described and
      clarify clinical features of the disease caused by N. meningitidis regarding its
      relevance for healthcare professionals.

PMID- 29203097
TI  - Euclea undulata Thunb.: Review of its botany, ethnomedicinal uses, phytochemistry
      and biological activities.
AB  - Euclea undulata (E. undulata) is traditionally used for the treatment of body
      pains, chest complaints, cough, diabetes, diarrhoea, headaches, heart diseases
      and toothaches in southern Africa. This study was aimed at reviewing the botany,
      ethnopharmacology and biological activities of E. undulata in southern Africa.
      Results presented in this study are based on review of literature using search
      engines such as Science Direct, Springerlink, Scopus, PubMed, Web of Science,
      BioMed Central and Google Scholar. Herbal medicine is prepared from the
      decoctions of the roots, bark and leaves, and extracts of these plant parts have
      demonstrated anticholinesterase, anti-inflammatory, antimicrobial,
      antimycobacterial, antiplasmodial, antioxidant and hypoglycaemic activities.
      Multiple classes of phytochemical compounds such alkaloids, diterpenes, fatty
      acids, flavonoids, glycosides, naphthoquinones, phenolics, phytosterols, reducing
      sugars, saponins and tannins have been isolated from the species. E. undulata has
      a lot of potential as herbal medicine in tropical Africa, and advanced research
      is required aimed at correlating its medicinal uses with the phytochemistry and
      pharmacological properties.

PMID- 29203098
TI  - Pattern of hepatitis C virus genotypes and subtypes circulating in war-stricken
      Khyber Pakhtunkhwa, Pakistan: Review of published literature.
AB  - Infection due to hepatitis C virus (HCV) is a major cause of fibrosis and
      hepatocellular carcinoma in Pakistan. In the current review, pattern of HCV
      genotypes and subtypes in Khyber Pakhtunkhwa province was ascertained in light of
      the available literature. After thorough analysis, genotype 3 (58.27%) was
      determined to be the leading HCV genotype, followed by genotypes 2 (12.39%), 1
      (9.54%) and 4 (0.86%). The proportions of genotypes 5 and 6 were recorded as
      0.09% and 0.22% respectively. Subtype wise, 3a accounted for 48.67%, followed by
      subtype 2a (10.91%), 3b (9.43%), 1a (5.84%), 1b (3.66%), 2b (1.45%) and genotype
      4 with its undefined subtypes contributed a portion of 0.86%. The cumulative
      share of subtypes 1c, 2c, 3c, 5a and 6a was less than 1%. In 11.51% cases, the
      subtype was untypeable while in 7.17% cases mixed subtypes were recorded. Gender
      wise, proportions of most HCV subtypes were marginally higher among males as
      compared to females. On the basis of studied groups, 3a was pervasive among all
      groups except in intravenous drug users where 2a was the major HCV subtype.
      Similarly, based on various geographical locations (provincial divisions),
      subtype 3a revealed a ubiquitous distribution. Conclusively, HCV 3a persists to
      be the principal subtype across the province of Khyber Pakhtunkhwa. The
      considerable number of untypeable subtypes in most studies urges for an improved
      genotyping system on the basis of local sequence data and practice of sequencing
      for determination of underlying subtype in untypeable cases. Further, studies on
      identification of subtypes transmission pattern are imperative for assessment of
      transmission origin and reinforcement of efficient control strategies. In
      addition, the current review emphasizes the need of attention toward HCV risk
      groups and ignored southern side of Khyber Pakhtunkhwa province for better
      holistic understanding of HCV genotype distribution pattern in the province.

PMID- 29203099
TI  - Effects of 8-Hydroxyisocapnolactone-2-3-diol and friedelin on mast cell
      degranulation.
AB  - OBJECTIVE: To investigate the effects of friedelin (terpenoid) and 8
      hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 MUM, 30 MUM, and
      100 MUM on inhibiting mast cells (MCs) degranulation. METHODS: The investigation
      was performed in vitro by administering each compound into rat peritoneal MCs and
      rat basophilic leukemia-2H3 cells followed by activation with 50 MUg/mL of
      compound 48/80 or 1 MUM of ionomycin. The concentration of histamine released
      from each group was measured by a high-performance liquid chromatography
      fluorometry system with post-column derivatization using o-phthalaldehyde.
      RESULTS: 8-Hydroxyisocapnolactone-2-3-diol inhibited degranulation of compound
      48/80 activated-rat peritoneal MCs with the histamine release percentages of
      74.57%, 72.21% and 51.79% when the 10 MUM, 30 MUM and 100 MUM concentrations were
      used, respectively. Where as about 81% histamine was released by the control
      group. Degranulation inhibition ability was also observed in ionomycin-activated
      rat basophilic leukemia-2H3 cells. In contrast, friedelin failed to inhibit
      degranulation in either cell type. The inhibition of 8-hydroxyisocapnolactone-2-3
      diol was not related to the depletion of histamine synthesis as implied by the
      total histamine measurement. CONCLUSIONS: These results exhibit the promising of
      8-hydroxyisocapnolactone-2-3-diol is a potential parent structure for developing
      a MCs stabilizer.

PMID- 29203100
TI  - Antioxidant, anti-inflammatory and antinociceptive potential of Ternstroemia
      sylvatica Schltdl. & Cham.
AB  - OBJECTIVE: To evaluate the anti-inflammatory, analgesic, antioxidant and acute
      toxicity of extracts obtained from a successive extraction with solvents of
      ascending polarity [hexane, hex; chloroform, CHCl3 and ethanol (EtOH)] of
      Ternstroemia sylvatica Schltdl. & Cham. METHODS: The antioxidant potential was
      evaluated by 2,2 diphenyl-1-picrylhydrazyl, the ferric reducing/antioxidant power
      assays and by determining the total phenolic content. The anti-inflammatory and
      antinociceptive effects were evaluated using the in vivo croton oil-induced ear
      edema, phorbol 12-myristate 13-acetate induced ear edema, carrageenan-induced paw
      edema, acetic acid-induced writhing and formalin murine models. The acute
      toxicity was tested using the Lorke's method in mice. RESULTS: The EtOH extract
      was the most active for the antioxidant potential tests diphenyl-1-picrylhydrazyl
      (68.70% inhibition), ferric reducing/antioxidant power [(2431.30 +/- 102.10) mmol
      Fe2+ and total polyphenols content (215.80 +/- 8.50) meqAG/g]. The anti
      inflammatory activity was evaluated by topical application of croton oil (2
      mg/ear dose) where the EtOH extract showed the strongest activity compared to the
      control group (45.13% inhibition), whereas in the phorbol 12-myristate 13-acetate
      model, at the same dose, the CHCl3 extract showed the highest inhibition
      (42.88%). In the carrageenan induced edema model, the EtOH extract showed a
      stronger inhibition compared to indomethacin (56.34% and 50.70% at doses of 250
      and 500 mg/kg of extract, respectively) during the first hour. Similarly, the
      same extract showed the highest analgesic activity (30.60% inhibition) in the
      acetic acid contortion assay, and in the formalin test it showed a greater effect
      with respect to the control group in both phases. CONCLUSIONS: Our work confirms
      the value of Ternstroemia sylvatica as an important anti-inflammatory and
      analgesic plant, whose mechanism seems to be associated to its antioxidant
      effects, and supports its uses in the Mexican traditional medicine.

PMID- 29203101
TI  - Efficient hepatoprotective activity of cranberry extract against CCl4-induced
      hepatotoxicity in Wistar albino rat model: Down-regulation of liver enzymes and
      strong antioxidant activity.
AB  - OBJECTIVE: To investigate the hepatoprotective efficacy of cranberry extract
      (CBE) against carbon tetrachloride (CCl4)-induced hepatic injury using in-vivo
      animal model. METHODS: The hepatoprotective efficacy of CBE (200 and 400 mg/kg)
      was investigated against CCl4 (4 mL/kg)-induced hepatotoxicity, elevated liver
      enzymes [ALT (alanine aminotransferase), AST (aspartate aminotransferase), and
      alkaline phosphatase (ALP)], and total protein (TP) contents in the serum.
      Moreover, CBE-aided antioxidant defense against hepatotoxic insult of CCl4 was
      measured by evaluating a number of anti-oxidative biomarkers including reduced
      glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and
      malondialdehyde (MDA) in the serum by using spectrophotometric analyses. RESULTS:
      Results showed that the exposure of experimental animals to CCl4 did induce
      significant hepatotoxicity compared to the non-induced (untreated) group. The
      oral administration of CBE demonstrated a significant dose-dependent alleviation
      in the liver enzymes (AST, ALT, and ALP), increased antioxidant defense (GSH,
      SOD, and CAT), and reduced MDA levels in the serum of treated animals compared to
      the animals without treatment. The resulting data showed that the administration
      of CBE decreased the serum levels of ALT, AST, and ALP compared to the CCl4
      induced group. CONCLUSIONS: The resulting data evidenced that CBE exhibits
      promising hepatoprotective potential against the chemical induced hepatotoxicity,
      maintains homeostasis in liver enzymes, and can provide significant antioxidant
      defense against free radicals-induced oxidative stress.

PMID- 29203102
TI  - Antimicrobial resistance and underlying mechanisms in Staphylococcus aureus
      isolates.
AB  - OBJECTIVE: To investigate the antimicrobial susceptibility of 97 clinical
      Staphylococcus aureus (S. aureus) strains against 14 antimicrobials and
      corresponding resistance mechanisms. METHODS: The antimicrobial susceptibility of
      the isolates was determined using a disk diffusion method and antimicrobial
      resistance genes were screened by polymerase chain reaction. Mutations
      responsible for ciprofloxacin and rifampicin resistance were investigated by
      polymerase chain reaction and DNA sequencing. RESULTS: All isolates were found to
      be susceptible to vancomycin. Various rates of resistance to penicillin (83.5%),
      ampicillin (77.3%), erythromycin (63.9%), tetracycline (16.5%),
      amoxicillin/clavulanic acid (16.5%), ciprofloxacin (15.5%),
      trimethoprim/sulfamethoxazole (15.5%), oxacillin (13.4%), fusidic acid (12.4%),
      rifampin (6.2%), clindamycin (6.2%), gentamicin (6.2%) and mupirocin (5.2%) were
      determined. In addition, different combinations of resistance genes were
      identified among resistant isolates. Ciprofloxacin resistant isolates had
      mutations in codon 84 (Ser84Leu) and 106 (Gly106Asp) in the gyrA gene. Mutations
      in grlA were mostly related to Ser80Phe substitution. Leu466Ser mutation in the
      rpoB gene was detected in all rifampin resistant isolates. All methicillin
      resistant S. aureus isolates were SCCmec type V. CONCLUSIONS: In conclusion, it
      was determined that the isolates were resistant to different classes of
      antimicrobials at varying rates and resistance was mediated by different genetic
      mechanisms. Therefore, continuous monitoring of resistance in S. aureus strains
      is necessary to control their resistance for clinically important antimicrobials.

PMID- 29203103
TI  - Association of TNFA (-308G/A), IFNG (+874 A/T) and IL-10 (-819 C/T) polymorphisms
      with protection and susceptibility to dengue in Brazilian population.
AB  - OBJECTIVE: To evaluate gene polymorphisms and their association with
      susceptibility to dengue. METHODS: A retrospective case-control study was
      performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue
      hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic
      profiles were identified using polymerase chain reaction based in real time and
      amplification-refractory mutation system. RESULTS: We observed a protective
      association of IL-10 (-819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34-0.91)
      against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01-4.38) and T/T (P =
      0.008, OR = 3.82, CI = 1.38-10.59) genotypes were associated with DHF and DF,
      respectively. The dominant model TNFA -308 GA + AA (P = 0.043, OR = 0.45, CI =
      0.20-1.00) genotypes were found to have protective effect against dengue
      infection. A protective association among the IFNG (+874 A/T) A/T genotype
      against DF (P = 0.02, OR = 0.46, CI = 0.24-0.89) and DHF (P = 0.034, OR = 0.43,
      CI = 0.19-0.95) was observed. When the studied single-nucleotide polymorphism was
      analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18
      7.41) was statistically significantly associated with susceptibility to DF and
      the combination GCT (P = 0.035, OR = 0.28, CI = 0.08-0.90) with protection
      against the development of DHF. CONCLUSIONS: This research identifies the
      association of the IFNG (+874 A/T), TNFA (-308G/A), IL-10 (-819 C/T) genotypes as
      a factor for protection, susceptibility and severity to dengue.

PMID- 29203104
TI  - Evaluating the effect of Myrtus communis on programmed cell death in hydatid cyst
      protoscolices.
AB  - OBJECTIVE: To evaluate the possible involvement of programmed cell death strategy
      in hydatid cyst protoscolices following treatment with Myrtus communis (M.
      communis) as an herbal medicine. METHODS: Protoscolices were aseptically
      collected from sheep liver hydatid cysts. Evaluating the effect of M. communis
      extract on programmed cell death and increased activity of caspases 3, 8, and 9
      in hydatid cyst protoscolices was conducted by treating the protoscolices with
      different concentration (5, 50, and 100 mg/mL) of M. communis extract at 37 
      degrees C and 5% CO2 for 4 h by using the Bradford test and ELISA commercial
      kits. RESULTS: The extract of M. communis at all concentrations led to initiation
      of programmed cell death in protoscolices and this effect, was only significant
      at 50 and 100 mg/mL concentrations, compared to the negative control (P < 0.05).
      Also, the activity of caspases 3, 8, and 9 in hydatid cyst protoscolices, was
      shown that the extract at all 3 concentrations could only increase the activity
      of caspases 3 and 9. Moreover, a significant increase in the activity of caspase
      3 was only observed at concentrations 50 and 100 mg/mL by 37.00% and 66.19% while
      a significant increase in the activity of caspase 9 at the same concentrations
      was observed by 20.89% and 63.67%, respectively (P < 0.05). CONCLUSIONS: The
      extract of M. communis at different concentrations could increase the activity of
      caspases 3 and 9 and caused programmed cell death in hydatid cyst protoscolices
      however, this effect was significant at high concentrations of the extract.

PMID- 29203105
TI  - Bartonella infection in asymptomatic horses and donkeys from Tuscany, Central
      Italy.
AB  - OBJECTIVE: To investigate the occurrence of Bartonella sp. infection in
      asymptomatic horses and donkeys living in Tuscany, Central Italy. METHODS: Blood
      samples were collected from 77 horses and 15 donkeys and tested by indirect
      immunofluorescent test to detect antibodies against Bartonella sp. and by PCR to
      detect the pathogen. RESULTS: Fifty-four (58.69%; 95% CI: 47.95%-68.87%) animals,
      9 donkeys and 45 horses, were seropositive with antibody titers ranging from 1:64
      to 1:512. PCR assays detected 9 horses positive for Bartonella sp. and 3 donkeys
      for Bartonella henselae genotype I. CONCLUSIONS: The detected sero-prevalence
      suggests a common and frequent exposure of equids living in Central Italy to
      bartonellae and PCR results show that Bartonella sp. infection is possible both
      in horses and donkeys. At the best of our knowledge, this is the first report of
      Bartonella henselae infection in donkeys.

PMID- 29203106
TI  - Oral pharmacological treatment for patent ductus arteriosus in premature neonates
      with hemodynamic repercussions.
AB  - OBJECTIVE: To evaluate the efficacy of oral indomethacin, ibuprofen, and
      paracetamol in oral dosage form on patent ductus arteriosus (PDA) in premature
      neonates with significant clinical and hemodynamic repercussions (CHRs) and to
      determine the effect of these respective treatments on renal function. METHODS: A
      retrospective study of cases of PDA in premature neonates in the Neonatal
      Intensive Care Unit was conducted. The treatments consisted of indomethacin [0.2
      mg/(kg.d), 3-day cycle], ibuprofen [10 mg/(kg.d) followed by 5 mg/(kg.d), 3-day
      cycle], and paracetamol (15 mg/kg every 6 h, 5-day cycle). The drugs were
      administered as an oral solution. The following variables were considered:
      gestational age, newborn weight at birth, Apgar score, diuresis, serum creatinine
      and urea levels, and serum electrolyte levels (sodium and potassium). RESULTS:
      Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus
      with a mean outcome period of 3.5 d. In premature neonates with CHRs and
      contraindications for indomethacin, the initial treatment with either ibuprofen
      or paracetamol failed to close the ductus. However, when this treatment was
      followed by indomethacin, closure occurred in 66.7% of the neonates, with an
      outcome period of 9.66 d. The initial treatment with one cycle of ibuprofen
      followed by one or two cycles of paracetamol failed to close the ductus.
      CONCLUSIONS: Oral indomethacin was effective for closure of the PDA in premature
      neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in
      premature neonates with severe CHRs and contraindications for indomethacin was
      ineffective. However, results in clinical improvements of neonates allowed the
      subsequent use of indomethacin and successful closure of the ductus. A
      significant reduction of diuresis occurred in neonates who were treated with
      indomethacin, either as a first-line treatment or after the failure of ibuprofen
      or paracetamol.

PMID- 29203107
TI  - Glypican-3-specific cytotoxic T lymphocytes induced by human leucocyte antigen
      A*0201-restricted peptide effectively kill hepatocellular carcinoma cells in
      vitro.
AB  - OBJECTIVE: To investigate potential human leucocyte antigen (HLA)-A2-restricted
      epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide
      specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC)
      cells. METHODS: The potential HLA-A*0201-restricted GPC3 peptides were screened
      using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA
      A*0201 complex assay. The peptide-specific CTLs were generated and their
      cytotoxicity against GPC3+ SMMC 7721 and HepG2 cells was detected using IFN-gamma
      based enzyme-linked immunospot and lactate dehydrogenase release assays in vitro.
      RESULTS: A total of six peptides were identified for bindings to HAL-A2 and the
      GPC3 522-530 and GPC3 229-237 peptides with HLA-A*0201 molecules displayed high
      binding affinity and stability. The CTLs induced by the GPC3 522-530 or positive
      control GPC3 144-152 peptide responded to the peptide by producing IFN-gamma,
      which were abrogated by treatment with anti-HLA-A2 antibody. The GPC3 522-530
      specific CTLs responded to and killed SMMC 7721 and HepG2 cells, instead of GPC3
      silenced SMMC 7721 or HepG2 cells. GPC3 522-530-specific CTLs response to HCC
      cells was blocked by anti-HLA-A2 antibody. CONCLUSIONS: The GPC3 522-530 peptide
      contains antigen-determinant and its specific CTLs can effectively kill HCC in a
      HLA-A2-restricted and peptide-dependent manner. Our findings suggest that this
      peptide may be valuable for development of therapeutic vaccine.

PMID- 29203108
TI  - Effect of taurine on immune function in mice with T-cell lymphoma during
      chemotherapy.
AB  - OBJECTIVE: To observe the effect of taurine on immune function in mice with T
      cell lymphoma during chemotherapy. METHODS: A total of 40 C57BL/6 mice were
      selected and randomly divided into 4 groups, namely model group, chemotherapy
      group, taurine group and chemotherapy + taurine group, each containing 10 mice.
      Hypodermic injection was adopted to inoculate EL-4 cells in order to establish
      model of T-cell lymphoma. When the tumor achieved the size of 1 cm3, intervention
      treatments were given to the groups respectively. Mice in model group received
      0.2 mL of normal saline which was intraperitoneally injected on Days 1, 8 and 15
      with 3 weeks as a cycle; mice in chemotherapy group were administered with 80
      mg/kg body weight of gemcitabine which was also intraperitoneally injected on
      Days 1, 8 and 15 with 3 weeks as a cycle; mice in taurine group were administered
      with 80 mg/kg body weight of taurine intraperitoneally injected daily for
      consecutive 8 d; mice in chemotherapy + taurine group were treated in the same
      manner as the mice in taurine group and chemotherapy group. Five mice were
      sacrificed at 2 and 3 weeks after intervention respectively, and the tumor
      tissues were collected and weighted after removal of auxiliary tissue, then the
      tumor inhibition rate was calculated. The thymus and spleen of mice sacrificed at
      3 weeks after intervention were collected and weighted, and thymus and spleen
      indexes were calculated. Enzyme linked immunosorbent assay was used to detect the
      serum levels of IL-4, IL-10, IL-12 and IFN-gamma in mice of each group. RESULTS:
      The tumor weights in chemotherapy group, taurine group and chemotherapy + taurine
      group after 2 and 3 weeks of treatment were significantly lower than that in
      model group (P < 0.05); the tumor weight in chemotherapy + taurine group after 2
      and 3 weeks of treatment was significantly lower than that in chemotherapy group
      (P < 0.05); the tumor inhibition rate in chemotherapy + taurine group was
      significantly higher than that in chemotherapy group and taurine group (P <
      0.05); the thymus and spleen indexes in taurine group and chemotherapy + taurine
      group were significantly higher than those in chemotherapy group and model group
      (P < 0.05); the thymus and spleen indexes in chemotherapy group were
      significantly lower than those in model group (P < 0.05); after 3 weeks of
      treatment, the serum levels of IL-4, IL-12 and IFN-gamma in chemotherapy group,
      taurine group and chemotherapy + taurine group were significantly lower than
      those in model group (P < 0.05); the IL-4 level in taurine group and chemotherapy
      + taurine group was significantly lower than that in chemotherapy group (P <
      0.05); the serum level of IL-10 in chemotherapy group and chemotherapy + taurine
      group was significantly higher than that in model group and taurine group (P <
      0.05); the serum level of IFN-gamma in taurine group and chemotherapy + taurine
      group was significantly lower than that in model group and chemotherapy group (P
      < 0.05); after treatment of 3 weeks, the serum levels of IL-4 and IL-10 in
      chemotherapy group, taurine group and chemotherapy + taurine group were
      significantly lower than those in model group (P < 0.05), and IL-12 level was
      significantly higher than that in model group (P < 0.05); the level of IFN-gamma
      in taurine group and chemotherapy + taurine group was significantly higher than
      that in model group (P < 0.05), while the level of IFN-gamma in chemotherapy
      group was significantly lower than that in the other 3 groups (P < 0.05).
      CONCLUSIONS: Taurine can effectively enhance the immune function of mice with T
      cell lymphoma during chemotherapy, reduce the toxicity of chemotherapy.

PMID- 29203109
TI  - Influence of light intensity and water content of medium on total dendrobine of
      Dendrobium nobile Lindl.
AB  - OBJECTIVE: To ascertain the influence of light intensity and water content of
      medium on the total dendrobine of Dendrobium nobile (D. nobile). METHOD: The
      principal component analysis combined with total dendrobine accumulation was
      conducted to assess the yield and quality of D. nobile in all treatments. In the
      experiment, D. nobile plants were cultivated in greenhouse as tested materials,
      and complete test of 9 treatments was adopted with relative light intensities
      75.02%, 39.74%, 29.93% and relative water content of medium 50%, 65%, 80%. The
      plants were treated in June and harvested till December. Indexes including
      agronomic traits, fresh weight and dry weight of stem and leaf, ash content,
      extract, and dendrobine were measured. RESULTS: Under the light intensity
      treatments of 75.02% with 50%, 65%, 80% water content of medium, the basal stems
      of plants were comparatively thicker with more leaves, and the fresh weight and
      dry weight of stems and leaves were significantly higher than other 6 treatments.
      Leaves in all treatments contained dendrobine. Under the light intensity
      treatments of 75.02% with 50%, 65%, 80% water content of medium, dendrobine
      content of leaves was lower while dendrobine contents of other treatments were
      more than 0.60%. After comprehensive assessment through the principal component
      analysis and total dendrobine accumulation, the results showed that 3 treatments
      with relative light intensity of 75.02% ranked the top three. CONCLUSIONS: In
      brief, the moderately strong light intensity and water content of medium from low
      to medium can facilitate the growth and yield of D. nobile plants, while light
      intensity from moderately weak to weak can enhance the dendrobine content.

PMID- 29203110
TI  - An atypical case of disseminated cutaneous leishmaniasis due to Leishmania
      peruviana in the valleys of Ancash-Peru.
AB  - We present an atypical case of disseminated cutaneous leishmaniasis in the Sihuas
      district, located in the Andean valleys of Ancash-Peru. A 62-year-old man with no
      particular medical history presented multiple lesions located on the inferior
      abdomen, lumbar region and the right anterior thigh. Histological analysis found
      leishmanial amastigotes in the lesion sample, the Montenegro reaction was
      positive for Leishmania spp, and the polymerase chain reaction was positive for
      Leishmania peruviana. In conclusion, the atypical presentation of this disease
      may be related to the presence of an uncommon parasite strain or host immune
      deficiencies. The molecular identification of the etiology for disseminated
      leishmaniasis, will allow a better understanding of the presentation and proper
      treatment, as well as associated risk factors.

PMID- 29203111
TI  - Staphylococcal (phospho)lipases promote biofilm formation and host cell invasion.
AB  - Most Staphylococcus aureus strains secrete two lipases SAL1 and SAL2 encoded by
      gehA and gehB. These two lipases differ with respect to their substrate
      specificity. Staphylococcus hyicus secretes another lipase, SHL, which is in
      contrast to S. aureus lipases Ca2+-dependent and has a broad-spectrum lipase and
      phospholipase activity. The aim of this study was to investigate the role of
      staphylococcal (phospho) lipases in virulence. For this we constructed a gehA
      gehB double deletion mutant in S. aureus USA300 and expressed SHL in agr-positive
      (accessory gene regulator) and agr-negative S. aureus strains. The lipases
      themselves have no hemolytic or cytotoxic activity. However, in agr-negative
      strains SHL-expression caused an upregulation of hemolytic activity. We further
      show that SHL-expression significantly enhanced biofilm formation probably due to
      an increase of extracellular DNA release. SHL-expression also increased host cell
      invasion 4-6-fold. Trioleate, a main triacylglycerol component of mammalian skin,
      induced lipase production. Finally, in the mouse sepsis and skin colonization
      models the lipase producing and mutant strain showed no significant difference
      compared to the WT strain. In conclusion, we show that staphylococcal lipases
      promote biofilm formation and host cell invasion and thereby contribute to S.
      aureus virulence.

PMID- 29203112
TI  - Suitability of 1-hexyl-3-methylimidazolium ionic liquids for the analysis of
      pharmaceutical formulations containing tricyclic antidepressants.
AB  - The reversed-phase chromatographic behaviour of six tricyclic antidepressants
      (amitryptiline, clomipramine, doxepin, imipramine, nortryptiline and maprotiline)
      was examined in this work with acetonitrile-water mobile phases, in the absence
      and presence of the ionic liquids 1-hexyl-3-methylimidazolium chloride and 1
      hexyl-3-methylimidazolium tetrafluoroborate, which have interesting features for
      the separation of basic compounds, in terms of peak shape combined with reduced
      retention. Tricyclic antidepressants are low polarity drugs that strongly
      associate to the alkyl chains of conventional stationary phases. They are also
      positively charged in the usual working pH range (2-8) in reversed-phase liquid
      chromatography, due to their strong basic character. In consequence, they may
      interact with the residual ionised silanols present in conventional silica-based
      stationary phases, which is translated in stronger retention, and tailed and
      broad peaks. A simple chromatographic procedure for the control of tricyclic
      antidepressants in pharmaceutical formulations was developed using a C8 column
      and a mobile phase containing 30% acetonitrile/10 mM 1-hexyl-3-methylimidazolium
      chloride at pH 3, with UV detection. Intra- and inter-day precisions were usually
      below +1.0%, and intra- and inter-day bias (trueness) ranged between -2.1% and
      +2.4%, and between -3.0% and +2.3%, respectively. Sample preparation was simple
      and only required solubilisation and filtration previous to injection.

PMID- 29203113
TI  - Improved separation by at-column dilution in preparative hydrophilic interaction
      chromatography.
AB  - We evaluated at-column dilution (ACD) as a possible approach to reduce peak
      distortion caused by the injection of strong solvents in preparative hydrophilic
      interaction chromatography (HILIC). Three model compounds, namely uridine,
      cytidine and guanosine were selected and injected either in conventional or ACD
      conditions, using various proportions of water and acetonitrile in the sample
      diluent. Plate number and peak capacity were systematically investigated under
      both isocratic and gradient elution conditions, respectively. In isocratic
      conditions, ACD was found to provide higher plate numbers with sample diluent
      containing more than 40% water, but lower plate numbers with injections of less
      than 40% water, in comparison to a conventional injection system at the
      preparative scale. These contrasting results were attributed to the fact that i)
      efficiency was fundamentally reduced in ACD, due to the low make-up flow rate
      that was used to flush the injection loop, but ii) the trend was reversed for
      highly aqueous injection thanks to the capacity of ACD to maintain similar
      efficiency regardless of the injection solvent. On the other hand, peak capacity
      was comparable between ACD and conventional systems in gradient elution for
      injections containing low amounts of water. However, ACD became increasingly
      advantageous as the proportion of water in the injection solvent and/or the
      injection volume increased. This was confirmed by the separation of a plant root
      aqueous extract. Altogether, our findings suggest that ACD is beneficial both in
      isocratic and gradient modes when strongly aqueous solutions are injected,
      offering an attractive approach to increase loadability, while preserving peak
      shapes in preparative HILIC.

PMID- 29203114
TI  - A simultaneous screening and quantitative method for the multiresidue analysis of
      pesticides in spices using ultra-high performance liquid chromatography-high
      resolution (Orbitrap) mass spectrometry.
AB  - A novel screening and quantitation method is reported for non-target multiresidue
      analysis of pesticides using ultra-HPLC-quadrupole-Orbitrap mass spectrometry in
      spice matrices, including black pepper, cardamom, chili, coriander, cumin, and
      turmeric. The method involved sequential full-scan (resolution = 70,000), and
      variable data independent acquisition (vDIA) with nine consecutive fragmentation
      events (resolution = 17,500). Samples were extracted by the QuEChERS method. The
      introduction of an SPE-based clean-up step through hydrophilic-lipophilic-balance
      (HLB) cartridges proved advantageous in minimizing the false negatives. For
      coriander, cumin, chili, and cardamom, the screening detection limit was largely
      at 2 ng/g, while it was 5 ng/g for black pepper, and turmeric. When the method
      was quantitatively validated for 199 pesticides, the limit of quantification
      (LOQ) was mostly at 10 ng/g (excluding black pepper, and turmeric with LOQ = 20
      ng/g) with recoveries within 70-120%, and precision-RSDs <20%. Furthermore, the
      method allowed the identification of suspected non-target analytes through
      retrospective search of the accurate mass of the compound-specific precursor and
      product ions. Compared to LC-MS/MS, the quantitative performance of this Orbitrap
      MS method had agreements in residue values between 78-100%.

PMID- 29203115
TI  - In situ preparation of multilayer coated capillary column with HKUST-1 for
      separation of neutral small organic molecules by open tubular capillary
      electrochromatography.
AB  - The popularity of novel nanoparticles coated capillary column has aroused
      widespread attention of researchers. Metal organic frameworks (MOFs) with special
      structure and chemical properties have received great interest in separation
      sciences. This work presents the investigation of HKUST-1 (Hong Kong University
      of Science and Technology-1, called Cu3(BTC)2 or MOF-199) nanoparticles as a new
      type of coating material for capillary electrochromatography. For the first time,
      three layers coating (3-LC), five layers coating (5-LC), ten layers coating (10
      LC), fifteen layers coating (15-LC), twenty layers coating(20-LC) and twenty-five
      layers coating (25-LC) capillary columns coated with HKUST-1 nanoparticles were
      synthesized by covalent bond with in situ, layer-by-layer self-assembly approach.
      The results of scanning electron microscopy (SEM), X-ray diffraction (XRD) and
      plasma atomic emission spectrometry (ICP-AES) indicated that HKUST-1 was
      successfully grafted on the inner wall of the capillary. The separating
      performances of 3-LC, 5-LC, 10-LC, 15-LC, 20-LC and 25-LC open tubular (OT)
      capillary columns were studied with some neutral small organic molecules. The
      results indicated that the neutral small organic molecules were separated
      successfully with 10-LC, 15-LC and 20-LC OT capillary columns because of the size
      selectivity of lattice aperture and hydrophobicity of organic ligands. In
      addition, 10-LC and 15-LC OT capillary columns showed better performance for the
      separation of certain phenolic compounds. Furthermore, 10-LC, 15-LC and 20-LC OT
      capillary columns exhibited good intra-day repeatability with the relative
      standard deviations (RSDs; %) of migration time and peak areas lying in the range
      of 0.3-1.2% and 0.5-4.2%, respectively. For inter-day reproducibility, the RSDs
      of the three OT capillary columns were found to be lying in the range of 0.3-5.5%
      and 0.3-4.5% for migration time and peak area, respectively. The RSDs of
      retention times for column-to-column for three batches of 10-LC, 15-LC and 20-LC
      OT capillary columns were in the range from 2.3% to 7.2%. Moreover, the
      fabricated 10-LC, 15-LC and 20-LC OT capillary columns exhibited good
      repeatability and stability for separation, which could be used successively for
      more than 120 runs with no observable changes on the separation efficiency.

PMID- 29203116
TI  - Diagnosis and management of metastatic neoplasms with unknown primary.
AB  - In cancer of unknown primary (CUP), metastases are clinically and histologically
      confirmed, but the primary tumor site remains elusive after extensive work-up.
      CUPs make up for 2-3% of all epithelial malignancies. The two prevailing
      histologies are adenocarcinomas and undifferentiated carcinomas, whereas squamous
      cell carcinomas, neuroendocrine carcinomas and rare histologies account for the
      remaining 10%. The diagnostic work-up in CUP relies strongly on a detailed
      immunohistological (IHC) analysis in order to characterize the tumor type,
      nowadays aided by molecular techniques. Diagnostics also include a thorough
      clinical examination, a basic lab draw with the most relevant tumor markers, and
      cross sectional imaging. Additional PET-CT is recommended in cervical lymph nodes
      suggestive of head and neck cancer and in limited metastases potentially
      treatable in curative intent. As for treatment, it is paramount to identify
      patients who fall into one of the six well defined "favorable" subset categories,
      namely extragonadal germ cell tumors, adenocarcinoma with isolated unilateral
      axillary lymph nodes in female patients, squamous cell carcinoma with neck lymph
      nodes, squamous cell carcinoma with inguinal lymph nodes, serous papillary
      peritoneal carcinomatosis in females and blastic bone metastasis in males with
      elevated PSA. These subsets are distinct both regarding the required treatment
      and the comparably favorable prognosis. Within the remaining "unfavorable" group,
      patients of colon and renal cancer type should be identified based on IHC and
      clinical picture, since the prognosis of these patients seems to improve with the
      use of therapy tailored to the presumed primary as well. For the few patients
      with limited metastases it should be assessed whether they are candidates for
      surgery, radiotherapy or surgery followed by irradiation in curative intent. The
      remaining majority of patients are treated with empiric palliative chemotherapy,
      typically a platinum - paclitaxel combination, though the level of evidence for
      this therapy recommendation is low. Gemcitabine alone or in combination can be
      used as an alternative. Decoding of the molecular profiles in CUP offers the
      prospect of targeted therapy with novel agents. However, there appears to be no
      uniform molecular pattern for CUP, and the observed molecular diversity thus
      poses a challenge to respective clinical trials.

PMID- 29203117
TI  - The Principles and Techniques of Benefit-Finding for Dementia Caregivers: Reply
      to Gersdorf.

PMID- 29203118
TI  - Emerging Trends in Undergraduate Medical Education: Implications for Geriatric
      Psychiatry.

PMID- 29203119
TI  - How the detector resolution affects the clinical significance of SBRT pre
      treatment quality assurance results.
AB  - PURPOSE: Aim of this work was to study how the detector resolution can affect the
      clinical significance of SBRT pre-treatment volumetric modulated arc therapy
      (VMAT) verification results. METHODS: Three detectors (PTW OCTAVIUS 4D 729, 1500
      and 100 SRS) used in five configurations with different resolution were compared:
      729, 729 merged, 1500, 1500 merged and 1000 SRS. Absolute local gamma passing
      rates of 3D pre-treatment quality assurance (QA) were evaluated for 150 dose
      distributions in 30 plans. Five different kinds of error were introduced in order
      to establish the detection sensitivity of the three devices. Percentage
      dosimetric differences were evaluated between planned dosevolume histogram (DVH)
      and patients' predicted DVH calculated by PTW DVH 4D(r) software. RESULTS: The
      mean gamma passing rates and the standard deviations were 92.4% +/- 3.7%, 94.6%
      +/- 1.8%, 95.3% +/- 4.2%, 97.4% +/- 2.5% and 97.6% +/- 1.4 respectively for 729,
      729 merged, 1500, 1500 merged and 1000 SRS with 2% local dose/2mm criterion. The
      same trend was found on the sensitivity analysis: using a tight gamma analysis
      criterion (2%L/1mm) only the 1000 SRS detected every kind of error, while 729 and
      1500 merged detected three and four kinds of error respectively. Regarding dose
      metrics extracted from DVH curves, D50% was within the tolerance level in more
      than 90% of cases only for the 1000 SRS. CONCLUSIONS: The detector resolution can
      significantly affect the clinical significance of SBRT pre-treatment verification
      results. The choice of a detector with resolution suitable to the investigated
      field size is of main importance to avoid getting false positive.

PMID- 29203120
TI  - Migfilin promotes migration and invasion in glioma by driving EGFR and MMP-2
      signalings: A positive feedback loop regulation.
AB  - Glioma is the most common type of primary brain tumors in the central nervous
      system (CNS). Migfilin occurs in human glioma and enhances cellular motility via
      the epidermal growth factor receptor (EGFR) pathway. However, the underlying
      molecular mechanism is not fully understood. In this study, we found that
      Migfilin promoted matrix metalloproteinase-2 (MMP-2) activity, and restrained the
      expression of tissue inhibitor of metalloproteinase 2 (TIMP2), which is an MMP-2
      inhibitor. Functional and structural studies showed that the LIM1 domain of
      Migfilin was required for Migfilin-mediated TIMP2 expression inhibition and MMP-2
      activity, and was also necessary in promoting cell motility. Furthermore,
      Migfilin-induced EGFR phosphorylation was greatly reduced by MMP-2 inhibitor
      (GM6001) or siRNA, while Migfilin-induced MMP-2 activation was also blocked by
      the EGFR inhibitor (AG1478) or siRNA. MMP-2 and EGFR inhibitors and their siRNAs
      can block Migfilin-induced migration and invasion, respectively. These results
      demonstrated that EGFR and MMP-2 signalings may form a positive feedback loop to
      enhance Migfilin-induced migration and invasion. Finally, we detected that the
      expression of Migfilin, EGFR phosphorylation (Tyr1173) and MMP-2 activity had a
      positive correlation in the clinical glioma sample. Taken together, these results
      suggest that Migfilin is a critical regulator in cellular motility by driving the
      EGFR-MMP-2 feedback loop, and may be considered as a potential therapeutic target
      in glioma.

PMID- 29203122
TI  - Inducing chondrogenesis in MSC/chondrocyte co-cultures using exogenous TGF-beta:
      a mathematical model.
AB  - The differentiation of mesenchymal stem cells (MSCs) into chondrocytes (native
      cartilage cells), or chondrogenesis, is a key step in the tissue engineering of
      articular cartilage, where the motility and high proliferation rate of MSCs used
      as seed cells are exploited. Chondrogenesis is regulated by transforming growth
      factor-beta (TGF-beta), a short-lived cytokine whose effect is prolonged by
      storage in the extracellular matrix. Tissue engineering applications require the
      complete differentiation of an initial population of MSCs, and two common
      strategies used to achieve this in vitro are (1) co-culture the MSCs with
      chondrocytes, which constitutively produce TGF-beta; or (2) add exogenous TGF
      beta. To investigate these strategies we develop an ordinary differential
      equation model of the interactions between TGF-beta, MSCs and chondrocyte. Here
      the dynamics of TGF-beta are much faster than those of the cell processes; this
      difference in time-scales is exploited to simplify subsequent model analysis.
      Using our model we demonstrate that under strategy 1 complete chondrogenesis will
      be induced if the initial proportion of chondrocytes exceeds a critical value.
      Similarly, under strategy 2 we find that there is a critical concentration of
      exogenous TGF-beta above which all MSCs will ultimately differentiate. Finally,
      we use the model to demonstrate the potential advantages of adopting a hybrid
      strategy where exogenous TGF-beta is added to a co-culture of MSCs and
      chondrocytes, as compared to using either strategy 1 or 2 in isolation.

PMID- 29203123
TI  - Unifying relationships between complexity and stability in mutualistic ecological
      communities.
AB  - Conserving ecosystem function and associated services requires deep understanding
      of the underlying basis of system stability. While the study of ecological
      dynamics is a mature and diverse field, the lack of a general model that predicts
      a broad range of theoretical and empirical observations has allowed unresolved
      contradictions to persist. Here we provide a general model of mutualistic
      ecological interactions between two groups and show for the first time how the
      conditions for bi-stability, the nature of critical transitions, and identifiable
      leading indicators in time-series can be derived from the basic parameters
      describing the underlying ecological interactions. Strong mutualism and
      nonlinearity in handling-time are found to be necessary conditions for the
      occurrence of critical transitions. We use the model to resolve open questions
      concerning the effects of heterogeneity in inter-species interactions on both
      resilience and abundance, and discuss these in terms of potential trade-offs in
      real systems. This framework provides a basis for rich investigations of
      ecological system dynamics, and may be generalizable across many ecological
      contexts.

PMID- 29203121
TI  - Using a memory systems lens to view the effects of estrogens on cognition:
      Implications for human health.
AB  - Understanding the organizing and activating effects of gonadal steroids on adult
      physiology can guide insight into sex differences in and hormonal influences on
      health and disease, ranging from diabetes and other metabolic disorders, emotion
      and stress regulation, substance abuse, pain perception, immune function and
      inflammation, to cognitive function and dysfunction accompanying neurological
      disorders. Because the brain is highly sensitive to many forms of estrogens, it
      is not surprising that many adult behaviors, including cognitive function, are
      modulated by estrogens. Estrogens are known for their facilitating effects on
      learning and memory, but it is becoming increasingly clear that they also can
      impair learning and memory of some classes of tasks and may do so through direct
      actions on specific neural systems. This review takes a multiple memory systems
      approach to understanding how estrogens can at the same time enhance hippocampus
      sensitive place learning and impair striatum-sensitive response learning by
      exploring the role estrogen receptor signaling may play in the opposing cognitive
      effects of estrogens. Accumulating evidence suggests that neither receptor
      subtype nor the timing of treatment, i.e. rapid vs slow, explain the
      bidirectional effects of estrogens on different types of learning. New findings
      pointing to neural metabolism and the provision of energy substrates by
      astrocytes as a candidate mechanism for cognitive enhancement and impairment are
      discussed.

PMID- 29203124
TI  - Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies
      model.
AB  - The tumor microenvironment is an integral component in promoting tumor
      development. Cancer-associated fibroblasts (CAFs), which reside in the tumor
      stroma, produce Hepatocyte Growth Factor (HGF), an important trigger for invasive
      and metastatic tumor behavior. HGF contributes to a pro-tumorigenic environment
      by activating its cognate receptor, c-Met, on tumor cells. Tumor cells, in turn,
      secrete growth factors that upregulate HGF production in CAFs, thereby
      establishing a dynamic tumor-host signaling program. Using a spatiotemporal
      multispecies model of tumor growth, we investigate how the development and spread
      of a tumor is impacted by the initiation of a dynamic interaction between tumor
      derived growth factors and CAF-derived HGF. We show that establishment of such an
      interaction results in increased tumor growth and morphological instability, the
      latter due in part to increased cell species heterogeneity at the tumor-host
      boundary. Invasive behavior is further increased if the tumor lowers
      responsiveness to paracrine pro-differentiation signals, which is a hallmark of
      neoplastic development. By modeling anti-HGF and anti-c-Met therapy, we show how
      disruption of the HGF/c-Met axis can reduce tumor invasiveness and growth,
      thereby providing theoretical evidence that targeting tumor-microenvironment
      interactions is a promising avenue for therapeutic development.

PMID- 29203125
TI  - Vascular Access Outcomes Reported in Maintenance Hemodialysis Trials: A
      Systematic Review.
AB  - BACKGROUND: Many randomized controlled trials have been performed with the goal
      of improving outcomes related to hemodialysis vascular access. If the reported
      outcomes are relevant and measured consistently to allow comparison of
      interventions across trials, such trials can inform decision making. This study
      aimed to assess the scope and consistency of vascular access outcomes reported in
      contemporary hemodialysis trials. STUDY DESIGN: Systematic review. SETTING &
      POPULATION: Adults requiring maintenance hemodialysis. SELECTION CRITERIA: All
      randomized controlled trials and trial protocols reporting vascular access
      outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane
      Kidney and Transplant Specialized Register from January 2011 to June 2016.
      INTERVENTIONS: Any hemodialysis-related intervention. OUTCOMES: The frequency and
      characteristics of vascular access outcome measures were analyzed and classified.
      RESULTS: From 168 relevant trials, 1,426 access-related outcome measures were
      extracted and classified into 23 different outcomes. The 3 most common outcomes
      were function (136 [81%] trials), infection (63 [38%]), and maturation (31
      [18%]). Function was measured in 489 different ways, but most frequently reported
      as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses"
      (30 [22%]). Infection was assessed in 136 different ways, with "number of access
      related infections" being the most common measure. Maturation was assessed in 44
      different ways at 15 different time points and most commonly characterized by
      vein diameter and blood flow. Patient-reported outcomes, including pain (19
      [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority
      of trials used previously standardized outcome definitions. LIMITATIONS:
      Restricted sampling frame for feasibility and focus on contemporary trials.
      CONCLUSIONS: The reporting of access outcomes in hemodialysis trials is very
      heterogeneous, with limited patient-reported outcomes and infrequent use of
      standardized outcome measures. Efforts to standardize outcome reporting for
      vascular access are critical to optimizing the comparability, reliability, and
      value of trial evidence to improve outcomes for patients requiring hemodialysis.

PMID- 29203126
TI  - ADPKD Progression in Patients With No Apparent Family History and No Mutation
      Detected by Sanger Sequencing.

PMID- 29203127
TI  - "Green Smoothie Cleanse" Causing Acute Oxalate Nephropathy.
AB  - Oxalate nephropathy is an uncommon condition that causes acute kidney injury with
      the potential for progression to end-stage renal disease. Diagnosis is based on
      the kidney biopsy findings of abundant polarizable calcium oxalate crystals in
      the epithelium and lumen of renal tubules. We report a case of acute oxalate
      nephropathy in a 65-year-old woman, temporally associated with the consumption of
      an oxalate-rich green smoothie juice "cleanse" prepared from juicing oxalate-rich
      green leafy vegetables and fruits. Predisposing factors included a remote history
      of gastric bypass and recent prolonged antibiotic therapy. She had normal kidney
      function before using the cleanse and developed acute kidney injury that
      progressed to end-stage renal disease. Consumption of such juice cleanses
      increases oxalate absorption, causing hyperoxaluria and acute oxalate nephropathy
      in patients with predisposing risk factors. Given the increasing popularity of
      juice cleanses, it is important that both patients and physicians have greater
      awareness of the potential for acute oxalate nephropathy in susceptible
      individuals with risk factors such as chronic kidney disease, gastric bypass, and
      antibiotic use.

PMID- 29203128
TI  - Arsenic Exposure in Incident Hemodialysis Patients.

PMID- 29203129
TI  - Corticosteroids in IgA Nephropathy.

PMID- 29203130
TI  - A pilot study of subthalamic theta frequency deep brain stimulation for cognitive
      dysfunction in Parkinson's disease.

PMID- 29203131
TI  - Electroconvulsive therapy and subsequent epilepsy in patients with affective
      disorders: A register-based Danish cohort study.
AB  - OBJECTIVE: It has been suggested that Electroconvulsive Therapy (ECT) might
      increase the risk of epilepsy but the few patient studies with retrospective data
      from medical records do not support the hypothesis. The aim of this study was to
      examine the relationship between ECT and subsequent incident epilepsy in patients
      with affective disorder. We also explored whether any association varied with
      number of ECTs and time since last treatment. METHODS: All 169,457 patients with
      first hospital contact for an affective disorder between January 2005 and
      December 2015 were identified in the Danish National Patient Registry and
      followed for incident epilepsy from January 2005 until November 2016. The
      association between ECT and epilepsy was examined using Cox proportional hazard
      regression with adjustment for gender, age, educational level, comorbid
      schizophrenia, previous stroke and antidepressant and antipsychotic medication
      use. RESULTS: A total of 5875 patients had at least one ECT and 1873 patients
      developed epilepsy (Incidence rate: 213 pr. 100,000 person years) during the
      follow-up of mean 5 years. In patients below age 40 years, ECT was associated
      with a higher rate of epilepsy after adjustment for covariables (Hazard Ratio
      (HR) = 1.84; 95% Confidence Intervals (CI) = [1.24-2.74]). In patients aged 41-60
      years ECT was not associated with epilepsy, while for those above 60 treated with
      ECT the rate was lower (HR = 0.57; (95% CI = [0.37-0.89]). CONCLUSION: In
      patients with affective disorders, we found a weak positive association between
      ECT and subsequent diagnosis of epilepsy in those younger than 40 years, and a
      weak negative association in patients older than 60 years. The associations might
      be subject to residual confounding from risk factors related to ECT.

PMID- 29203132
TI  - Deaths in France: Characteristics, place of death, hospitalisations and use of
      palliative care during the year before death.
AB  - AIM: Only limited data are available concerning the diseases managed and the
      hospital pathway before death. The aim of this study was to describe diseases,
      hospitalisations, and use of palliative care one year before death as well as
      place of death in France. METHODS: French health insurance general scheme
      beneficiaries who died in 2013 were identified in the National Health Insurance
      Information System (SNIIRAM) with a selection of information concerning their
      various hospital stays, including hospital palliative care (HPC) and nursing home
      care. Diseases were identified by algorithms from reimbursement data recorded in
      the SNIIRAM database. RESULTS: A total of 347 253 people were included (61% of
      all deaths in France). The mean age of death was 77 years (SD 15.1). Diseases
      managed before death were cardiovascular/neurovascular diseases (56%), cancers
      (42%), neurological and degenerative diseases (25%), diabetes (21%) and chronic
      respiratory diseases (20%). Deaths occurred in hospital in 60% of cases: 51% in
      acute wards, 6% in rehabilitation units, 3% in hospital at home (HaH), and 13% in
      nursing homes. During the year preceding death, 84% of people were hospitalised
      at least once and 29% received HPC. People receiving HPC more often died in
      hospital than people not receiving HPC (69% vs. 44%). CONCLUSION: Health
      administrative data from the SNIIRAM database can refine our knowledge of the
      care pathway prior to death and of the use of hospital palliative care and can be
      useful to evaluate the new governmental palliative care plan recently deployed in
      France.

PMID- 29203134
TI  - Proteomic profiling of large myofibrillar proteins from dried and long-term
      stored polyacrylamide gels.
AB  - A method for the utilization of dried polyacrylamide gels from the pre-proteomic
      era is described in order to enable the mass spectrometric analysis of long-term
      stored protein preparations. The in-gel digestion of high-molecular-mass proteins
      embedded in a 20-year old gel was carried out following gel re-swelling and
      resulted in the proteomic identification of a large number of proteins, including
      3400 kDa titin, 800 kDa nebulin and myosin heavy chains of 220 kDa from rabbit
      skeletal muscle. These findings demonstrate that dried protein gels from past
      biochemical analyses can be successfully reused and analyzed by modern and
      refined mass spectrometric techniques.

PMID- 29203133
TI  - [Primary care: A definition of the field to develop research].
AB  - BACKGROUND: Research in the field of primary care has dramatically increased in
      France in recent years, especially since 2013 with the introduction of primary
      care as a thematic priority for research proposals launched by the Ministry of
      Health (Direction generale de l'offre de soins). MATERIAL AND METHODS: The RECaP
      (Research in Clinical Epidemiology and Public Health) network is a French
      research network supported by Inserm, which recently implemented a specific
      working group focusing on research in primary care, based on a multidisciplinary
      approach. Researchers from different specialties participate in this group. The
      first aim of the group was to reach a common definition of the perimeter and of
      the panel of healthcare professionals and structures potentially involved in the
      field of primary care. For this purpose, a selection of different data sets of
      sources defining primary care was analyzed by the group, each participant
      collecting a set of sources, from which a synthesis was made and discussed.
      RESULTS: A definition of primary care at different levels (international,
      European and French) was summarized. A special attention was given to the French
      context in order to adapt the perimeter to the characteristics of the French
      healthcare system, notably by illustrating the different key elements of the
      definition with the inclusion of primary care actors and the type of practice
      premises. CONCLUSION: In conclusion, this work illustrates the diversity of
      primary care in France and the potential offered for research purposes.

PMID- 29203135
TI  - Exploring three different expression systems for recombinant expression of
      globins: Escherichia coli, Pichia pastoris and Spodoptera frugiperda.
AB  - Globins are among the best investigated proteins in biological and medical
      sciences and represent a prime tool for the study of the evolution of genes and
      the structure-function relationship of proteins. Here, we explore the recombinant
      expression of globins in three different expression systems: Escherichia coli,
      Pichia pastoris and the baculovirus infected Spodoptera frugiperda. We expressed
      two different human globin types in these three expression systems: I) the well
      characterized neuroglobin and II) the uncharacterized, circular permutated globin
      domain of the large chimeric globin androglobin. It is clear from the literature
      that E.coli is the most used expression system for expression and purification of
      recombinant globins. However, the major disadvantage of E. coli is the formation
      of insoluble aggregates. We experienced that, for more complex multi-domain
      globins, like the chimeric globin androglobin, it is recommended to switch to a
      higher eukaryotic expression system.

PMID- 29203136
TI  - Microplate chemiluminescent assay for HBV DNA detection using 3-(10'
      phenothiazinyl)propionic acid/N-morpholinopyridine pair as enhancer of HRP
      catalyzed chemiluminescence.
AB  - A sensitive sandwich assay for hepatitis B virus (HBV) DNA detection based on use
      of commercial CL-ELISA microplates was developed. To reveal the target the
      covalent conjugate of reporter oligonucleotide and horseradish peroxidase (HRP)
      was synthesized. An employment of enhanced chemiluminescence reaction, where 3
      (10'-phenothiazinyl)propionic acid/N-morpholinopyridine pair was used as enhancer
      of HRP-catalyzed chemiluminescence, permitted to measure the enzyme activity of
      the conjugate with high sensitivity. Under the favorable conditions the limit of
      detection and a linear range of the assay were 3 pM and 0.07-2.0 nM,
      respectively. The coefficient of variation (CV) for determination of HBV DNA
      concentrations within the working range was lower than 4%. The obtained results
      demonstrated that the developed assay had high sensitivity and precision.

PMID- 29203137
TI  - Mucoadhesive chitosan-coated solid lipid nanoparticles for better management of
      tuberculosis.
AB  - Taking into consideration the potential mucoadhesion properties of systems in
      lung delivery, this paper describes the preparation and characterization of
      chitosan-coated solid lipid nanoparticles (C-SLNs) loaded with rifampicin (RIF)
      as anti-tuberculosis (anti-TB) drug. The process of development and
      characterization of the NPs in terms of size, surface charge, encapsulation
      efficiency (EE), morphology, in vitro drug release, differential scanning
      calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vitro
      assessment of mucoadhesive property, cell viability and permeability studies are
      documented. Results showed that the SLNs had a smooth spherical shape with a size
      of ca. 245-344 nm and with a zeta potential around -30 mV for SLNs and +40 mV for
      C-SLNs. The surface charge variation from negative to positive charge and FTIR
      analysis demonstrated the successful process of coating the nanoparticles (NPs)
      surface with chitosan. The DSC thermograms were in agreement with the
      nanostructure of the SLNs. The EE of drug was found to be higher than 90% and the
      loading capacity (LC) around 4.5%. C-SLNs show higher in vitro muchoadesive
      properties and a higher permeability in alveolar epithelial cells A549 than
      uncoated SLNs, indicating that the developed C-SLNs can be used as a promising
      carrier for sasfer and efficient management of TB.

PMID- 29203138
TI  - Systemic Israeli acute paralysis virus (IAPV) infection in bumblebees (Bombus
      terrestris) through feeding and injection.
AB  - Israeli acute paralysis virus (IAPV) can cause a systemic infection, resulting in
      mortality in both Apis and Bombus spp. bees. However, little is known about the
      virus infection dynamics within bee tissues. Here, we established systemic IAPV
      infections in reared bumblebee Bombus terrestris workers through feeding and
      injection and investigated the mortality, tissue tropism and viral localization.
      Injection of approximately 500 IAPV (IAPVinj stock) particles resulted in acute
      infection, viral loads within tissues that were relatively stable from bee to
      bee, and a distinctive tissue tropism, making this method suitable for studying
      systemic IAPV infection in bumblebees. Feeding with approximately 1 * 106
      particles of the same virus stock did not result in systemic infection. A high
      concentration stock of IAPV (IAPVfed stock) allowed us to feed bumblebees with
      approximately 1 * 109 viral particles, which induced both chronic and acute
      infection. We also observed a higher variability in viral titers within tissues
      and less clear tissue tropism during systemic infection, making feeding with
      IAPVfed stock less optimal for studying IAPV systemic infection. Strikingly, both
      infection methods and stocks with different viral loads gave a similar viral
      localization pattern in the brain and midgut of bumblebees with an acute
      infection. The implications of these findings in the study of the local immunity
      in bees and barriers to oral transmission are discussed. Our data provide useful
      information on the establishment of a systemic viral infection in bees.

PMID- 29203139
TI  - Structural Mapping of Adenosine Receptor Mutations: Ligand Binding and Signaling
      Mechanisms.
AB  - The four adenosine receptors (ARs), A1, A2A, A2B, and A3, constitute a subfamily
      of G protein-coupled receptors (GPCRs) with exceptional foundations for structure
      based ligand design. The vast amount of mutagenesis data, accumulated in the
      literature since the 1990s, has been recently supplemented with structural
      information, currently consisting of several inactive and active structures of
      the A2A and inactive conformations of the A1 ARs. We provide the first integrated
      view of the pharmacological, biochemical, and structural data available for this
      receptor family, by mapping onto the relevant crystal structures all site
      directed mutagenesis data, curated and deposited at the GPCR database (available
      through http://www.gpcrdb.org). This analysis provides novel insights into ligand
      binding, allosteric modulation, and signaling of the AR family.

PMID- 29203140
TI  - Coordination or Coincidence? The Relationship between Prolactin and Gonadotropin
      Secretion.
AB  - A recent paper demonstrates that kisspeptin can stimulate the secretion of both
      prolactin and luteinizing hormone (LH). This provides novel insight into
      mechanisms that could account for previous observations of concordant patterns of
      secretion of the two hormones, such as pulsatile secretion with simultaneous
      pulses, as well as the preovulatory surges of both prolactin and LH.

PMID- 29203141
TI  - Interacting Cancer Machineries: Cell Signaling, Lipid Metabolism, and
      Epigenetics.
AB  - Cancer-specific perturbations of signaling, metabolism, and epigenetics can be a
      cause and/or consequence of malignant transformation. Evidence indicates that
      these regulatory systems interact with each other to form highly flexible and
      robust cybernetic networks that promote malignant growth and confer treatment
      resistance. Deciphering these plexuses using holistic approaches known from
      systems biology can be instructive for the future design of novel anticancer
      strategies. In this review, I discuss novel findings elucidating the multiple
      molecular interdependence among cancer-specific signaling, cell metabolism, and
      epigenetics to provide an insightful understanding of how major cancer
      machineries interact with each other during cancer development and progression,
      and how this knowledge may be used for future co-targeting strategies.

PMID- 29203142
TI  - Synthesis and evaluation of a potent, well-balanced EP2/EP3 dual agonist.
AB  - A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is
      described. Optimization of the lead compound was accomplished in consideration of
      the relative agonist activity against each EP subtype receptor and the
      pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4
      hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4
      carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0
      nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold).
      Further fine-tuning of compound 10 led to identification of ONO-8055 as a
      clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg,
      po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey
      model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly
      promising drug for UAB.

PMID- 29203144
TI  - A broad-host range dual-fluorescence reporter system for gene expression analysis
      in Gram-negative bacteria.
AB  - Fluorescence-based reporter systems are valuable tools for studying gene
      expression dynamics in living cells. Here we describe a dual-fluorescence
      reporter system carrying the red fluorescent marker mCherry and the blue
      fluorescent protein EBFP2 enabling the simultaneous analysis of two promoters in
      broad-host range autofluorescent Gram-negative bacteria.

PMID- 29203143
TI  - Synthesis and bioevaluation study of novel N-methylpicolinamide and
      thienopyrimidine derivatives as selectivity c-Met kinase inhibitors.
AB  - Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing
      pyridazinone were designed and synthesized and evaluated for the IC50 values
      against three cancer cell lines (A549, HepG2 and MCF-7) and some selected
      compounds were further evaluated for the activity against c-Met, Flt-3, VEGFR-2,
      c-Kit and EGFR kinases. Three compounds (35, 39 and 43) showed more active than
      positive control Foretinib against A549, HepG2 and MCF-7 cell lines. The most
      promising compound 43 showed superior activity against A549, HepG2 and MCF-7,
      with the IC50 values of 0.58 +/- 0.15 uM, 0.47 +/- 0.06 uM and 0.74 +/- 0.12 uM,
      which were 3.73-5.39-fold more activity than Foretinib, respectively. The
      experiments of enzyme-based showed that 43 restrain the c-Met selectively, with
      the IC50 values of 16 nM, which showed equal activity to Foretinib (14 nM) and
      better than the compound 5 (90 nM). Moreover, AO and Annexin V/PI staining and
      docking studies were carried out.

PMID- 29203145
TI  - Global gene expression analysis of macrophage response induced by nonporous and
      porous silica nanoparticles.
AB  - Little is known about the global gene expression profile of macrophages in
      response to changes in size and porosity of silica nanoparticles (SNPs).
      Spherical nonporous SNPs of two different diameters, and mesoporous spherical
      SNPs with comparable size were characterized. Reactive oxygen species,
      mitochondrial membrane potential, lysosome degradation capacity, and lysosome pH
      were measured to evaluate the influence of nonporous and mesoporous SNPs on
      mitochondrial and lysosomal function. RNA-sequencing was utilized to generate
      transcriptional profiles of RAW264.7 macrophages exposed to non-toxic SNP doses.
      DESeq2, limma, and BinReg2 software were used to analyze the data based on both
      unsupervised and supervised strategies to identify genes with greatest
      differences among NP treatments. Utilizing GATHER and DAVID software, possible
      induced pathways were studied. We found that mesoporous silica nanoparticles are
      capable of altering gene expression in macrophages at doses that do not elicit
      acute cytotoxicity, while gene transcription was minimally affected by nonporous
      SNPs.

PMID- 29203147
TI  - Interrelation of periodontal parameters between asthmatics and nonasthmatics
      subjects: a systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this systematic review (SR) is to evaluate the association
      between asthma and periodontal parameters. METHODS: An electronic search without
      date or language restrictions was carried out in MEDLINE, Cochrane, Web of
      Science, and LILACS until May 2017. In addition, manual search and in the grey
      literature were also conducted. The search process, data analysis, and quality
      assessment were performed by two independent reviewing authors. Eligibility
      criteria included prospective and retrospective cohort studies, case-controls,
      and randomized clinical trials. For the meta-analysis, the inverse variance
      method was used in fixed or random effect models, which were chosen according to
      heterogeneity. The estimates of the intervention effects were expressed as the
      mean differences. RESULTS: The search and selection process yielded 21 studies,
      published between 1979 and 2017. The meta-analysis showed a statistically
      significant difference for the parameters of gingival bleeding, plaque index, and
      gingival index for asthmatic participants with P<0.0001, P<0.0001, and P=0.0005,
      respectively. CONCLUSIONS: The data from this SR suggest that asthmatic patients
      may be more susceptible to negative periodontal changes, althought further high
      quality research wuold be welcome.

PMID- 29203146
TI  - Toward detection of toxoplasmosis from urine in mice using hydro-gel
      nanoparticles concentration and parallel reaction monitoring mass spectrometry.
AB  - Diagnosis of clinical toxoplasmosis remains a challenge, thus limiting the
      availability of human clinical samples. Though murine models are an approximation
      of human response, their definitive infection status and tissue availability make
      them critical to the diagnostic development process. Hydrogel mesh nanoparticles
      were used to concentrate antigen to detectable levels for mass spectrometry.
      Seven Toxoplasma gondii isolates were used to develop a panel of potential
      peptide sequences for detection by parallel reaction monitoring (PRM) mass
      spectrometry. Nanoparticles were incubated with decreasing concentrations of
      tachyzoite lysate to explore the limits of detection of PRM. Mice whose
      toxoplasmosis infection status was confirmed by quantitative real-time PCR had
      urine tested by PRM after hydrogel mesh concentration for known T. gondii
      peptides. Peptides from GRA1, GRA12, ROP4, ROP5, SAG1, and SAG2A proteins were
      detected by PRM after nanoparticle concentration of urine, confirming detection
      of T. gondii antigen in the urine of an infected mouse.

PMID- 29203148
TI  - Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin;
      involvement of autophagy, inflammation and oxidative stress.
AB  - Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus
      (DM), remains as one of the major causes of vision loss worldwide. The release of
      pro-inflammatory cytokines and the adhesion of leukocytes to retinal capillaries
      are initial events in DR development. Inflammation, ER stress, oxidative stress
      and autophagy are major causative factors involved in the pathogenesis of DR.
      Diabetes associated hyperglycemia leads to mitochondrial electron transport chain
      dysfunction culminating in a rise in ROS generation. Since mitochondria are the
      major source of ROS production, oxidative stress induced by mitochondrial
      dysfunction also contributes to the development of diabetic retinopathy.
      Autophagy increases in the retina of diabetic patients and is regulated by ER
      stress, oxidative stress and inflammation-related pathways. Autophagy functions
      as a double-edged sword in DR. Under mild stress, autophagic activity can lead to
      cell survival while during severe stress, dysregulated autophagy results in
      massive cell death and may have a role in initiation and exacerbation of DR.
      Melatonin and its metabolites play protective roles against inflammation, ER
      stress and oxidative stress due to their direct free radical scavenger activities
      and indirect antioxidant activity via the stimulation antioxidant enzymes
      including glutathione reductase, glutathione peroxidase, superoxide dismutase and
      catalase. Melatonin also acts as a cell survival agent by modulating autophagy in
      various cell types and under different conditions through amelioration of
      oxidative stress, ER stress and inflammation. Herein, we review the possible
      effects of melatonin on diabetic retinopathy, focusing on its ability to regulate
      autophagy processes.

PMID- 29203149
TI  - Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate
      brachytherapy.
AB  - PURPOSE: Hydrogel spacers have been suggested to limit rectal radiation dose with
      improvements in clinical outcomes in patients undergoing external beam radiation
      treatment for prostate cancer. No studies to date have assessed the utility and
      dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and
      Drug Administration-approved hydrogel rectal spacer, for high-dose-rate (HDR)
      brachytherapy. METHODS: Eighteen consecutive patients scheduled for HDR
      brachytherapy in the treatment of prostate cancer underwent transperineal
      ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter
      implantation. Treatment plans were generated using an inverse planning simulated
      annealing algorithm. Rectal dosimetry for these 18 patients was compared with the
      36 preceding patients treated with HDR brachytherapy without SpaceOAR. RESULTS:
      Fifty-four plans were analyzed. There was no difference in age, pretreatment
      prostate-specific antigen, Gleason score, clinical stage, prostate volume, or
      contoured rectal volume between those who received SpaceOAR and those who did
      not. Patients who received SpaceOAR hydrogel had significantly lower dose to the
      rectum as measured by percent of contoured organ at risk (median, V80 < 0.005%
      vs. 0.010%, p = 0.003; V75 < 0.005% vs. 0.14%, p < 0.0005; V70 0.09% vs. 0.88%, p
      < 0.0005; V60 = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for
      rectal volume in cubic centimeters. One patient who received SpaceOAR developed a
      perineal abscess 1 month after treatment. CONCLUSIONS: Transperineal insertion of
      SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases
      rectal radiation dose. Further investigation is needed to assess the clinical
      impact of this dosimetric improvement and potential toxicity reduction.

PMID- 29203150
TI  - Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and
      Infused HIV and Oncology Patients.
AB  - Replication-competent retrovirus/lentivirus (RCR/L) and insertional oncogenesis
      are potential safety risks with integrating viruses in gene-modified cell
      therapies. As such, the Food and Drug Administration guidances outline RCR/L
      monitoring methods throughout the entire gene therapy treatment cycle. We present
      data for 17 vector lots, 375 manufactured T cell products, and 308 patients post
      infusion across both HIV and oncology indications, showing no evidence of RCR/L.
      Given our data, a Poisson probability model estimates that a single patient, or a
      group of patients, would need to be followed for at least 52.8 years to observe
      one positive RCR/L event, highlighting the unlikelihood of RCR/L development.
      Additionally, we estimate the median time for lentivirus-modified T cell products
      to fall below the 1% vector sequence threshold in peripheral or whole blood that
      would trigger vector integration site analysis. These estimated times are 1.4
      months in hematologic malignancies, 0.66 month in solid tumors, and 0.92 month in
      HIV. Based on these considerable safety data in HIV and oncology and recent
      Biologics License Applications filed for lentiviral-modified T cell products for
      hematologic malignancies, this may be an opportune time to re-evaluate the
      current guidelines for T cell gene therapy product testing and long-term patient
      monitoring.

PMID- 29203151
TI  - Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of
      midazolam containing cyclodextrin.
AB  - INTRODUCTION: In the absence of a licensed formulation in many countries
      worldwide, ADV6209, an innovative 2mg/ml oral solution of midazolam containing
      cyclodextrin, has been developed for moderate sedation in paediatric patients.
      Population pharmacokinetics for ADV6209 is reported. METHODS: Plasma
      concentration data were collected from 37 paediatric patients and 12 healthy
      adults recruited in a single dose, open-label phase II pharmacokinetic study and
      in a single dose, randomised, open-label two-period crossover bioavailability
      study, respectively. Data were analysed using non-linear mixed effect modelling.
      Plasma concentrations of midazolam were described by a two-compartment model. An
      additional one-compartment model was added for alpha- hydroxymidazolam. RESULTS:
      The body weight covariate was found to have a significant impact on midazolam and
      alpha-hydroxymidazolam clearance, and on midazolam volume of distribution. The
      population pharmacokinetic model indicated that 77% of the midazolam dose was
      absorbed within 30min after oral administration. Parameter estimations for a
      subject of 34kg indicated values of midazolam clearance of 34.7l.h-1, a central
      volume of distribution of 27.9l and a peripheral volume of distribution of 413l.
      A higher metabolic ratio and a higher midazolam clearance per body weight were
      observed in the youngest group of subjects, in accordance with literature data.
      The clearance per body weight of alpha-hydroxymidazolam remained constant over
      the different age groups. CONCLUSION: Pharmacokinetic parameters were close to
      those reported in the literature with midazolam extemporaneous oral solutions or
      syrups, demonstrating that cyclodextrin had no significant effect on measured
      parameters.

PMID- 29203152
TI  - Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery
      of sumatriptan succinate.
AB  - In-vitro permeation studies were conducted to assess the feasibility of
      fabricating dissolving-microneedle-array systems to release sumatriptan
      succinate. The formulations consisted mainly of the encapsulated active
      ingredient and a water-soluble biologically compatible polymer,
      polyvinylpyrrolidone (PVP), approved by the U.S. Food and Drug Administration
      (FDA). Tests with Franz-type diffusion cells and Gottingen minipig skins showed
      an increase of the transdermal flux compared to passive diffusion. A preparation,
      containing 30% by mass of PVP and 8.7mg sumatriptan, produced a delivery rate of
      395+/-31MUg/cm2h over a 7-hour period after a negligible lag time of
      approximately 39min. Theoretically, a 10.7cm2 microneedle-array patch loaded with
      118.8mg of the drug would provide the required plasma concentration, 72ng/mL, for
      nearly 7h.

PMID- 29203153
TI  - Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's
      disease: a pilot study.
AB  - BACKGROUND: Ablative neurosurgery has been used to treat Parkinson's disease for
      many decades. MRI-guided focused ultrasound allows focal lesions to be made in
      deep brain structures without skull incision. We investigated the safety and
      preliminary efficacy of unilateral subthalamotomy by focused ultrasound in
      Parkinson's disease. METHODS: This prospective, open-label pilot study was done
      at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del
      Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly
      asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic
      surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric
      disease, or a skull density ratio of 0.3 or less were excluded. Enrolled patients
      underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus
      was targeted by means of brain images acquired with a 3-Tesla MRI apparatus.
      Several sonications above the definitive ablation temperature of 55 degrees C
      were delivered and adjusted according to clinical response. The primary outcomes
      were safety and a change in the motor status of the treated hemibody as assessed
      with part III of the Movement Disorders Society-Unified Parkinson's Disease
      Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6
      months. Adverse events were monitored up to 48 h after treatment and at scheduled
      clinic visits at 1, 3, and 6 months after treatment. The study is registered with
      ClinicalTrials.gov, number NCT02912871. FINDINGS: Between April 26 and June 14,
      2016, ten patients with markedly asymmetric parkinsonism that was poorly
      controlled pharmacologically were enrolled for focused ultrasound unilateral
      subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been
      recorded, none of which were serious or severe. Seven adverse events were present
      at 6 months. Three of these adverse events were directly related to
      subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost
      resolved by 6 months); on-medication dyskinesia in the treated arm (one patient,
      resolved after levodopa dose reduction); and subjective speech disturbance (one
      patient). Four of the adverse events present at 6 months were related to medical
      management (anxiety and fatigue [one patient each] and weight gain [two
      patients]). The most frequent adverse events were transient gait ataxia (related
      to subthalamotomy, six patients), transient pin-site head pain (related to the
      head frame, six patients), and transient high blood pressure (during the
      procedure, five patients). Transient facial asymmetry (one patient) and moderate
      impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in
      the treated hemibody improved by 53% from baseline to 6 months in the off
      medication state (16.6 [SD 2.9] vs 7.5 [3.9]) and by 47% in the on-medication
      state (11.9 [3.1] vs 5.8 [3.5]). INTERPRETATION: MRI-guided focused ultrasound
      unilateral subthalamotomy was well tolerated and seemed to improve motor features
      of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large
      randomised controlled trials are necessary to corroborate these preliminary
      findings and to assess the potential of such an approach to treat Parkinson's
      disease. FUNDING: Fundacion de investigacion HM Hospitales and Insightec.

PMID- 29203154
TI  - Subthalamotomy for Parkinson's disease: back to the future?

PMID- 29203155
TI  - Special Issue on Bioconversion of Food Wastes.

PMID- 29203156
TI  - [IgG4-related kidney disease: Urologist trap?]

PMID- 29203157
TI  - [Anticoagulation impact on bleeding risk during HoLEP: Monocentric study of 156
      patients].
AB  - OBJECTIVE: Compare the length of hospital stay and the complications after HoLEP
      between three groups of patients: a control group, a group with antiplatelet
      therapy, a group with anticoagulation therapy. MATERIALS: Retrospective cohort
      study that included all consecutive patients who underwent HoLEP for prostatic
      hyperplasia in our center from may 2013 to may 2016. Anticoagulated patients and
      patients under clopidogrel had respectively a relay with heparine and aspirine.
      Patients were seen after surgery at 1 and 3 months. RESULTS: A hundred and fifty
      six patients were analysed, mean age was 70.7 years (DS 6.8), mean prostate
      volume 88.8g (DS 34.1). 106 patients were in the control group, 34 had
      antiplatelet therapy and 16 had anticoagulation therapy. There were no difference
      between the 3 groups for mean age, mean prostatic volume, PSA. There was also no
      difference for length of intervention, irrigated volume and length of
      morcellation between the three groups. There were no difference between patients
      in the control group and patients with antiplatelet therapy for length of
      hospital stay (2.1 days vs 2.0 days), lenght of urethral catheterization (1.6
      days vs 1.5 days). There was a statistical difference between patients in the
      control group and patients with anticoagulation therapy for lenght of hospital
      stay (2.0 days vs 4.4 days; P=0.01), length of bladder irrigation (0.9 day vs 1.8
      days; P=0.01), lenght of urethral catheterization (1.6 days vs 3.5 days; P=0.01).
      Transfusion rate was 18.75% (n=3) for patients with anticoagulation, 2.9% (n=1)
      for patients under antiplatelet therapy and 0.9% (n=1) for patients in the
      control group. CONCLUSION: Anticoagulation during HoLEP is a valid option but
      need to be proceed with carefully management. LEVEL OF PROOF: 4.

PMID- 29203158
TI  - Are concurrent systematic cores needed at the time of targeted biopsy in patients
      with prior negative prostate biopsies?
AB  - INTRODUCTION AND OBJECTIVES: MRI-guided targeted biopsies are advised in patients
      who have undergone an initial series of negative systematic biopsies, in whom
      prostate cancer (PCa) suspicion remains elevated. The aim of the study was to
      evaluate whether, in men with prior negative prostate biopsies, systematic cores
      are also warranted at the time of an MRI-targeted repeat biopsy. MATERIAL AND
      METHODS: We enrolled patients with prior negative biopsy undergoing real time
      MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016.
      Patients with at least one index lesion on multiparametric MRI were included. All
      eligible patients underwent both systematic random biopsies (12-14 cores) and
      targeted biopsies (2-4 cores). RESULTS: The study included 74 men with a median
      age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The
      overall PCa detection rate and the clinically significant cancer detection rate
      were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar
      clinically significant PCa detection rate compared to systematic cores (33.8% vs.
      28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination
      approach was significantly superior to a targeted-only in overall PCa detection
      (+16.7% overall detection rate, P=0.007). Although differences in clinically
      significant PCa detection were statistically non-significant (P=0.13), a
      combination approach did allow detecting 7 extra clinically significant PCas
      (+13.8%). CONCLUSIONS: In patients with elevated PSA and prior negative biopsies,
      concurrent systematic sampling may be needed at the time of targeted biopsy in
      order to maximize PCa detection rate. Larger studies are needed to validate our
      findings. LEVEL OF EVIDENCE: 4.

PMID- 29203159
TI  - Long-term follow-up of tonsillectomy efficacy in children with PFAPA syndrome.
AB  - INTRODUCTION: The role of tonsillectomy in the periodic fever, aphthous
      stomatitis, pharyngitis, and adenitis, PFAPA syndrome, is controversial. Although
      some studies reported high success rates with tonsillectomy, further
      investigations are needed with larger numbers of patients. OBJECTIVE: To seek the
      long-term outcomes of tonsillectomy in PFAPA syndrome. METHODS: Case series;
      multi-center study. The study comprised 23 patients with PFAPA syndrome who
      underwent surgery (tonsillectomy with or without adenoidectomy) between January
      2009 and November 2014. RESULTS: 21 (91%) of 23 patients had complete resolution
      immediately after surgery. One patient had an attack 24h after surgery, but has
      had no further attacks. One patient had three attacks with various intervals, and
      complete remission was observed after 3 months. CONCLUSIONS: Tonsillectomy is a
      good option for the treatment of PFAPA syndrome.

PMID- 29203160
TI  - Myocardial strain may predict exercise tolerance in patients with reduced and mid
      range ejection fraction.
AB  - BACKGROUND: Conventional echocardiographic parameters, such as rest ejection
      fraction, perform poorly in the prediction of exercise tolerance in heart
      failure. The aim of the present study was to evaluate the contribution of
      hemodynamic instability in the observed lower functional capacity and investigate
      the role of left ventricular strain for the prediction of stress test duration in
      obese hypertensive patients with reduced ejection fraction. METHODS: Sixty-one
      patients with reduced ejection fraction underwent treadmill exercise
      echocardiography. Systolic and diastolic echocardiographic parameters were
      recorded. Moreover, the presence of hemodynamic instability was assessed through
      N-terminal pro B-type natriuretic peptide (NT-proBNP) measurements at baseline
      and peak exercise. RESULTS: Rest and peak NT-proBNP levels, and their difference,
      were significantly correlated with mean global strain at peak, which was the only
      parameter associated with changes in NT-proBNP levels. Rest and peak mean global
      strain were found to be predictive for the duration of treadmill stress test. In
      particular, mean global strain, but not left ventricular ejection fraction, was
      independently correlated with exercise ability. CONCLUSIONS: Stress
      echocardiography may provide important information regarding exercise tolerance
      in obese hypertensive patients with reduced ejection fraction, mainly through the
      evaluation of left ventricular strain. The obtained evidence may also have
      prognostic value, particularly in the early stages of the syndrome.

PMID- 29203161
TI  - Echocardiography and cardiac arrhythmias.
AB  - Cardiac arrhythmias refer to any abnormality or disturbance in the normal
      activation sequence of the myocardium and may be indicative of structural heart
      disease and the cause of significant cardiovascular complications and sudden
      cardiac death. The following review summarizes the current state-of-the-art
      knowledge on the role of echocardiography in the management of cardiac
      arrhythmias and focuses on atrial fibrillation and ventricular arrhythmias where
      echocardiography presents a particular diagnostic and prognostic interest.
      Moreover, a brief reference is made to the effect of cardiac arrhythmias and
      conduction abnormalities on echocardiographic examination.

PMID- 29203162
TI  - Diabetes mellitus doubles the risk of type 2 cardiorenal syndrome: results from
      the NHANES trial.

PMID- 29203163
TI  - Novel biomarkers in heart failure: How they change clinical decision?

PMID- 29203164
TI  - Atrial fibrillation and hypertrophic cardiomyopathy: co-existing conditions with
      additive risks.

PMID- 29203165
TI  - Sex hormone levels in the brain of d-aspartate-treated rats.
AB  - d-Aspartate (d-Asp) is an endogenous amino acid present in the central nervous
      system and endocrine glands of various animal taxa. d-Asp is implicated in
      neurotransmission, physiology of learning, and memory processes. In gonads, it
      plays a crucial role in sex hormone synthesis. We have investigated the effects
      of chronic (30 days d-Asp drinking solution) and acute (i.p. injection of
      2MUmol/g bw d-Asp) treatments on sex steroid synthesis in rat brain. Furthermore,
      to verify the direct effect of d-Asp on neurosteroidogenic enzyme activities,
      brain homogenates were incubated with different substrates (cholesterol,
      progesterone, or testosterone) with or without the addition of d-Asp. Enzyme
      activities were measured by evaluating the in vitro conversion rate of (i)
      cholesterol to progesterone, testosterone, and 17beta-estradiol, (ii)
      progesterone to testosterone and 17beta-estradiol, (iii) testosterone to 17beta
      estradiol. We found that d-Asp oral administration produced an increase of
      approximately 40% in progesterone, 110% in testosterone, and 35% in 17beta
      estradiol. Similarly, the results of the acute experiment showed that at 30min
      after d-Asp treatment, the progesterone, testosterone, and 17beta-estradiol
      levels increased by 29-35%, and at 8h they further increased by a 100% increment.
      In vitro experiments demonstrate that the addition of d-Asp to brain
      homogenate+substrate induces a significant increase in progesterone, testosterone
      and 17beta-estradiol suggesting that the amino acid upregulates the local
      activity of steroidogenic enzymes.

PMID- 29203166
TI  - Current Status of Cardio-Oncology in Spain: A National Multidisciplinary Survey.

PMID- 29203167
TI  - Antithrombotic Therapy After Percutaneous Aortic Valve Implantation: Large Gaps
      for a Matter of Extreme Importance.

PMID- 29203168
TI  - Selection of the Best of 2017 in Clinical Cardiology. Therapeutic Novelties.

PMID- 29203169
TI  - Antithrombotic Therapy After Percutaneous Aortic Valve Implantation: Large Gaps
      for a Matter of Extreme Importance. Response.

PMID- 29203170
TI  - Diameter of fluorescent microspheres determines their distribution throughout the
      cortical watershed area in mice.
AB  - A hemodynamic mechanism has long been assumed to play an important role in
      watershed infarction. In recent years, however, clinical evidence has indicated
      that an embolic mechanism is involved. The mechanism by which emboli are trapped
      preferentially in watershed areas remains unclear. In the present study, we
      developed a mouse embolus model using fluorescent microspheres with different
      diameters and evaluated the role of the microspheres' diameters in the generation
      of a watershed-patterned distribution. We injected fluorescent microspheres of
      four different diameters (i.e., 13, 24, 40, and 69 MUm) into the internal carotid
      artery of C57BL/6 mice either (1) without ligation of the common carotid artery
      (normal perfusion pressure model: NPPM) or (2) with ligation of the common
      carotid artery (low perfusion pressure model: LPPM). Left common carotid artery
      ligation induced reductions in local cerebral blood flow in both the periphery
      and the core area of the left middle cerebral artery. A greater reduction in the
      border-zone area between the left anterior cerebral artery and the middle
      cerebral artery was also noted. After 24 h, the brains were removed and the
      distribution of the microspheres in the brain was evaluated using a fluorescence
      microscope. The 24-MUm microspheres were distributed in the watershed area more
      frequently than the other microsphere sizes (P < .05, ANOVA followed by Tukey's
      test). Meanwhile, the distribution rates were similar between the NPPM and LPPM
      models for all microsphere sizes. This study suggested that the distribution
      pattern of the microspheres was only affected by the microspheres' diameters.

PMID- 29203171
TI  - The NLRP3 Inflammasome Renders Cell Death Pro-inflammatory.
AB  - NLRP3 is the most studied inflammasome sensor due to its crucial involvement in
      sterile and infection-triggered inflammation. Although its molecular mode of
      activation remains to be defined, it is well established that low intracellular
      potassium concentrations result in its activation. This functionality allows the
      classical NLRP3 pathway to serve as a highly sensitive, but non-specific
      surveillance mechanism responding to any type of perturbation that breaches
      plasma membrane integrity and the associated potassium gradient across the
      membrane. Here, we review our current knowledge on potassium efflux-dependent
      NLRP3 activation, with a special focus on how major cell death programs are
      rendered pro-inflammatory by secondary NLRP3 activation. Apart from the
      "alternative inflammasome" as the major exception to the rule, this connection
      explains the fundamental importance of NLRP3 in cell death-associated
      inflammation and firmly establishes NLRP3 as a principal surveillance mechanism
      of cellular integrity.

PMID- 29203172
TI  - How much do cancer specialists earn? A comparison of physician fees and
      remuneration in oncology and radiology in high-income countries.
AB  - The main driver of higher spending on health care in the US is believed to be
      substantially higher fees paid to US physicians in comparison with other
      countries. We aim to compare physician incomes in radiology and oncology
      considering differences in relation to fees paid, physician capacity and volume
      of services provided in five countries: the United States, Canada, Australia,
      France and the United Kingdom. The fee for a consultation with a specialist in
      oncology varies threefold across countries, and more than fourfold for
      chemotherapy. There is also a three to fourfold variation in fees for ultrasound
      and CT scans. Physician earnings in the US are greater than in other countries in
      both oncology and radiology, more than three times higher than in the UK;
      Canadian oncologists and radiologists earn considerably more than their European
      counterparts. Although challenging, benchmarking earnings and fees for similar
      health care activities across countries, and understanding the factors that
      explain any differences, can provide valuable insights for policy makers trying
      to enhance efficiency and quality in service delivery, especially in the face of
      rising care costs.

PMID- 29203173
TI  - Evaluation of the dynamic predictors of fluid responsiveness in dogs receiving
      goal-directed fluid therapy.
AB  - OBJECTIVES: Goal-directed fluid therapy (GDFT) based on pulse pressure variation
      (PPV) was used in anaesthetized dogs undergoing abdominal surgeries. The aims
      were 1) to evaluate the success rate of the PPV >=13% in detecting fluid
      responsiveness [delta stroke volume (DeltaSV) >=10%]; 2) to assess the
      correlation between PPV, systolic pressure variation (SPV), Plethysmograph
      Variability Index (PVI) and central venous pressure (CVP) and 3) to establish the
      threshold value for the PVI that would predict a PPV value of >=13% and
      indirectly discriminate responders from nonresponders to fluid therapy. STUDY
      DESIGN: Clinical, prospective, interventional study. ANIMALS: A total of 63
      client-owned dogs scheduled for abdominal procedures. METHODS: PPV and SPV were
      calculated manually from the invasive blood pressure trace on the Datex monitor.
      PVI was recorded from the Masimo pulse oximeter. Fluid challenge (10 mL kg-1
      Compound Sodium Lactate) was performed when PPV was >=13% and/or mean arterial
      pressure (MAP) < 60 mmHg. Fluid responsiveness was assessed by the
      transoesophageal Doppler probe. Cardiovascular parameters (heart rate, MAP, PPV,
      SPV, PVI, SV and if available, CVP) were measured before and after each fluid
      intervention. RESULTS: PPV >= 13% reliably predicted fluid responsiveness in
      82.9% of cases. There was positive correlation between PPV and SPV (r = 0.84%),
      PPV and logPVI (r = 0.46) as well as SPV and logPVI (r = 0.45). Noninvasive PVI
      value >=13% should predict PPV threshold value (13%) with 97% sensitivity and 68%
      specificity. There was no statistically significant correlation between PPV and
      CVP. CONCLUSIONS: PPV is a useful clinical tool to detect occult hypovolaemia and
      predict cardiovascular response to fluid challenge. Use of PPV is recommended as
      a part of GDFT in dogs undergoing abdominal procedures.

PMID- 29203174
TI  - The efficacy and safety of first-line single-agent chemotherapy regimens in low
      risk gestational trophoblastic neoplasia: A network meta-analysis.
AB  - OBJECTIVE: There is no consensus regarding what should be the optimal single
      agent regimen in low-risk gestational trophoblastic neoplasia(LRGTN). we
      performed this network meta-analysis(NMA) and our aim is to synthesize all
      efficacy evidence, enabling a comparison of all single-agent methotrexate(MTX)
      based or actinomycin-d(Act-D)-based regimens in LRGTN. METHODS: We performed a
      literature search of PubMed, Embase, and the Cochrane Library for all relevant
      articles. Seven randomized controlled trials and four retrospective studies met
      the study eligibility criteria. Overall, 987 patients were included. Treatments
      were grouped into weekly intramuscular MTX(w-IM MTX), five-day intramuscular
      MTX(5d-IM MTX), five-day intravenous MTX(5d-IV MTX), eight-day intramuscular MTX
      with folinic acid(MTX-FA), five-day intravenous Act-D(5d-IV Act-D), and bi-weekly
      pulsed intravenous Act-D (pulsed IV Act-D) treatments. P-score was used to rank
      the treatments. RESULTS: Values of P-score indicated that the Act-D-based
      regimens had superior efficacy compared with the MTX-based regimens. Namely, 5d
      IV Act-D had the highest probability of being the best treatment arm for CR,
      followed by pulsed IV Act-D and 5d-IV MTX. Similar results were observed in the
      subgroup analysis from the prospective studies. Toxicity analysis indicated that
      5d-IM MTX showed increased toxicity in nausea and vomiting, as measured by their
      P-scores. In contrast, 5d-IV Act-D had the highest probability of being the least
      toxic regimen in terms of nausea and vomiting. Grade 3/4 adverse events (AEs),
      though infrequent, were more frequently observed in 5d-IM MTX, followed by 5d-IV
      Act-D and 5d-IV MTX. CONCLUSIONS: Our NMA provides a systematic evaluation of the
      relative efficacy of available single-agent MTX-based and Act-D-based regimes in
      LRGTN. Until new evidence becomes available, 5d-IV Act-D and pulsed IV Act-D
      appear to be the best treatment options in LRGTN.

PMID- 29203175
TI  - Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical
      cancers treated with radical radio (chemo) therapy - A prospective observational
      study.
AB  - OBJECTIVE: With an aim to investigate the impact of Human Papilloma Virus (HPV)
      16/18 infection on clinical outcomes in locally advanced cervical cancers treated
      with radical radio (chemo) therapy, we undertook this prospective study. METHODS:
      Between May 2010 and April 2012, 150 histologically proven cervical cancer
      patients treated with radio (chemo) therapy were accrued. Cervical
      biopsies/brushings were collected at pre-treatment, end of treatment and at 3
      monthly intervals up to 24months. Quantitative estimation of HPV 16/18 was done
      using real-time polymerase chain reaction (RT-PCR) and correlated with various
      clinical end-points. RESULTS: Out of 150 patients accrued, 135 patients were
      considered for final analysis. Pre-treatment HPV16/18 DNA was detected in 126
      (93%) patients, with HPV-16 present in 91%. The mean log (+/-SD) HPV-16 and HPV
      18 viral load at pre-treatment was 4.76 (+/-2.5) and 0.14 (+/-2.1) copies/10ng of
      DNA, respectively. Though significant decline in viral load was observed on
      follow-ups (p<0.0001); by 9-month follow-up, 89 (66%) patients had persistence of
      HPV infection. Patients with persistent HPV 16/18 infection had a significantly
      higher overall and loco-regional relapses [44/89 (49%) and 29/89 (32%)] as
      compared to HPV clearance by 9months [12/43 (28%) and 5/43 (11%)] with p=0.024
      and p=0.02, respectively. Also, persistent HPV infection by 24-month showed a
      significant impact on loco-regional control (LRC) and recurrence-free survival
      (RFS). CONCLUSION: In locally advanced cervical cancers treated with radical
      radio (chemo) therapy, persistent HPV 16/18 infection is significantly high in
      immediate post-treatment period and correlated with higher loco-regional, overall
      relapses and was also associated with early relapses.

PMID- 29203176
TI  - Corrigendum to "Indications for and complications of transfusion and the
      management of gynecologic malignancies" [Gynecol. Oncol. 146 (2017) 416-426].

PMID- 29203177
TI  - Characterisation, analysis of expression and localisation of the opsin gene
      repertoire from the perspective of photoperiodism in the aphid Acyrthosiphon
      pisum.
AB  - Organisms exhibit a wide range of seasonal responses as adaptions to predictable
      annual changes in their environment. These changes are originally caused by the
      effect of the Earth's cycles around the sun and its axial tilt. Examples of
      seasonal responses include floration, migration, reproduction and diapause. In
      temperate climate zones, the most robust variable to predict seasons is the
      length of the day (i.e. the photoperiod). The first step to trigger photoperiodic
      driven responses involves measuring the duration of the light-dark phases, but
      the molecular clockwork performing this task is poorly characterized.
      Photopigments such as opsins are known to participate in light perception, being
      part of the machinery in charge of providing information about the luminous state
      of the surroundings. Aphids (Hemiptera: Aphididae) are paradigmatic photoperiodic
      insects, exhibiting a strong induction to diapause when the light regime mimics
      autumn conditions. The availability of the pea aphid (Acyrthosiphon pisum) genome
      has facilitated molecular approaches to understand the effect of light stimulus
      in the photoperiodic induction process. We have identified, experimentally
      validated and characterized the expression of the full opsin gene repertoire in
      the pea aphid. Among identified opsin genes in A. pisum, arthropsin is absent in
      most insects sequenced to date (except for dragonflies and two other hemipterans)
      but also present in a crustacean, an onychophoran and chelicerates. We have
      quantified the expression of these genes in aphids exposed to different
      photoperiodic conditions and at different times of the day and localized their
      transcripts in the aphid brain. Clear differences in expression patterns were
      found, thus relating opsin expression with the photoperiodic response.

PMID- 29203178
TI  - Fruit flies may face a nutrient-dependent life-history trade-off between
      secondary sexual trait quality, survival and developmental rate.
AB  - Optimal life-history strategies are those that best allocate finite environmental
      resources to competing traits. We used the geometric framework for nutrition to
      evaluate life-history strategies followed by Drosophila melanogaster by measuring
      the condition-dependent performance of life-history traits, including the
      morphology of male secondary sexual characters, sex combs. We found that
      depending on their rearing environment flies faced different forms of trait trade
      offs and accordingly followed different life-history strategies. High-energy,
      high-carbohydrate, low-protein diets supported development of the largest and
      most symmetrical sex combs, however, consistent with handicap models of sexual
      selection these foods were associated with reduced fly survival and developmental
      rate. Expressing the highest quality sex combs may have required secondary sexual
      trait quality to be traded-off with developmental rate, and our results indicated
      that flies unable to slow development died. As larval nutritional environments
      are predominantly determined by female oviposition substrate choice, we tested
      where mated female flies laid the most eggs. Mothers chose high-energy, high
      protein foods associated with rapid larval development. Mothers avoided high
      carbohydrate foods associated with maximal sex comb expression, showing they may
      avoid producing fewer 'sexy' sons in favour of producing offspring that develop
      rapidly.

PMID- 29203180
TI  - In this Issue November 2017.

PMID- 29203179
TI  - Neurotransmitters in the mediation of cerebral ischemic injury.
AB  - Under physiological conditions, neurotransmitters shape neuronal networks and
      control several cellular and synaptic functions. In the mammalian central nervous
      system (CNS), excitatory and inhibitory neurotransmission are mediated in large
      part by glutamate and gamma-aminobutyric acid (GABA), which are excitatory and
      inhibitory neurotransmitters, respectively. Glutamate and GABA also play crucial
      roles in neurological disorders such as cerebral ischemia. Glutamate in
      particular causes excitotoxicity, known as one of the hallmark mechanisms in the
      pathophysiology of cerebral ischemic injury for more than thirty years.
      Excitotoxicity occurs due to excessive glutamate release leading to
      overactivation of postsynaptic glutamate receptors, which evokes a downstream
      cascade that eventually leads to neuronal dysfunction and degeneration. Also, a
      reduction in GABA receptor response after ischemia impedes these inhibitory
      effectors from attenuating excitotoxicity and thereby further enabling the
      excitotoxic insult. This review focuses on the mechanisms by which glutamate and
      GABA mediate excitotoxicity and ischemic injury. This article is part of the
      Special Issue entitled 'Cerebral Ischemia'.

PMID- 29203181
TI  - Rotavirus strain diversity in Eastern and Southern African countries before and
      after vaccine introduction.
AB  - BACKGROUND: The African Rotavirus Surveillance Network has been detecting and
      documenting rotavirus genotypes in the African sub-continent since 1998 in
      anticipation of the rollout of rotavirus vaccination in routine Expanded
      Programme on Immunisation. This paper reports distribution of the rotavirus
      strains circulating in 15 Eastern and Southern African (ESA) countries from 2010
      2015 as part of active World Health Organization (WHO) rotavirus surveillance,
      and investigates possibility of emergence of non-vaccine or unusual strains in
      six selected countries post-vaccine introduction. MATERIAL AND METHODS: Stool
      samples were collected from children <5 years of age presenting with acute
      gastroenteritis at sentinel hospitals pre- and post-rotavirus vaccine
      introduction. Samples were tested for group A rotavirus using an enzyme
      immunoassay by the national and sentinel laboratories. At the WHO Rotavirus
      Regional Reference Laboratory in South Africa, molecular characterisation was
      determined by PAGE (n = 4186), G and P genotyping (n = 6447) and DNA sequencing
      for both G and P types (n = 400). RESULTS: The six-year surveillance period
      demonstrated that 23.8% of the strains were G1P[8], followed by G2P[4] (11.8%),
      G9P[8] (10.4%), G12P[8] (4.9%), G2P[6] (4.2%) and G3P[6] (3.7%) in 15 ESA
      countries. There was no difference in circulating strains pre- and post-rotavirus
      vaccine introduction with yearly fluctuation of strains observed over time.
      Atypical rotavirus G and P combinations (such as G1P[4], G2P[8], G9P[4] and
      G12P[4]) that might have arisen through inter-genogroup or inter-genotypes
      reassortment were detected at low frequency (2%). Close genetic relationship of
      African strains were reflected on the phylogenetic analysis, strains segregated
      together to form an African cluster in the same lineages/sub-lineage or
      monophyletic branch. CONCLUSION: There has been considerable concern about strain
      replacement post-vaccine introduction, it was not clear at this early stage
      whether observed cyclical changes of rotavirus strains were due to vaccine
      pressure or this was just part of natural annual fluctuations in the six ESA
      countries, long-term surveillance is required.

PMID- 29203183
TI  - The IL-1 family of cytokines. Do they have a role in scleroderma fibrosis?
AB  - Systemic sclerosis is a profibrotic autoimmune disease mediated by the
      dysregulation in collagen synthesis, leading to the increased deposition of
      collagens, primarily type I and III, and the deposition of other extracellular
      matrix proteins in the skin and internal organs, in a mechanism that is thought
      to be an over active wound healing process. These patients experience significant
      morbidity and the mortality rate in this disease is high. Indeed, scleroderma is
      the most deadly of diseases in the autoimmune spectrum. Recent evidence has
      placed the assembly and chronic activation of the inflammasome as a central
      driver of fibrosis. Once assembled, the inflammasome is a large protein complex
      that regulates the release of IL-1, IL-18, and IL-33, which are thought to play a
      role in the fibrotic response. IL-36 also belongs to the IL-1 family of cytokines
      and is a new comer to this field of research. Recent analyses of the IL-1 family
      of cytokines have demonstrated that many of them play a role in skin inflammation
      and fibrosis and their corresponding antagonists (IL-1RA and IL-36RA) can
      abrogate this pathology. Understanding how these cytokines are regulated and how
      they contribute to fibrosis will be important to understanding this pathology and
      may shed light in new areas for therapeutic development.

PMID- 29203182
TI  - The generation of a simian adenoviral vectored HCV vaccine encoding genetically
      conserved gene segments to target multiple HCV genotypes.
AB  - BACKGROUND: Hepatitis C virus (HCV) genomic variability is a major challenge to
      the generation of a prophylactic vaccine. We have previously shown that HCV
      specific T-cell responses induced by a potent T-cell vaccine encoding a single
      strain subtype-1b immunogen target epitopes dominant in natural infection.
      However, corresponding viral regions are highly variable at a population level,
      with a reduction in T-cell reactivity to these variants. We therefore designed
      and manufactured second generation simian adenovirus vaccines encoding genomic
      segments, conserved between viral genotypes and assessed these for
      immunogenicity. METHODS: We developed a computer algorithm to identify HCV
      genomic regions that were conserved between viral subtypes. Conserved segments
      below a pre-defined diversity threshold spanning the entire HCV genome were
      combined to create novel immunogens (1000-1500 amino-acids), covering variation
      in HCV subtypes 1a and 1b, genotypes 1 and 3, and genotypes 1-6 inclusive. Simian
      adenoviral vaccine vectors (ChAdOx) encoding HCV conserved immunogens were
      constructed. Immunogenicity was evaluated in C57BL6 mice using panels of genotype
      specific peptide pools in ex-vivo IFN-Upsilon ELISpot and intracellular cytokine
      assays. RESULTS: ChAdOx1 conserved segment HCV vaccines primed high-magnitude,
      broad, cross-reactive T-cell responses; the mean magnitude of total HCV specific
      T-cell responses was 1174 SFU/106 splenocytes for ChAdOx1-GT1-6 in C57BL6 mice
      targeting multiple genomic regions, with mean responses of 935, 1474 and 1112
      SFU/106 against genotype 1a, 1b and 3a peptide panels, respectively. Functional
      assays demonstrated IFNg and TNFa production by vaccine-induced CD4 and CD8 T
      cells. In silico analysis shows that conserved immunogens contain multiple
      epitopes, with many described in natural HCV infection, predicting immunogenicity
      in humans. CONCLUSIONS: Simian adenoviral vectored vaccines encoding genetic
      segments that are conserved between all major HCV genotypes contain multiple T
      cell epitopes and are highly immunogenic in pre-clinical models. These studies
      pave the way for the assessment of multi-genotypic HCV T-cell vaccines in humans.

PMID- 29203184
TI  - A Novel Modification of Transurethral Enucleation and Resection of the Prostate
      in Patients With Prostate Glands Larger than 80 mL: Surgical Procedures and
      Clinical Outcomes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the modified transurethral
      enucleation and resection of the prostate (M-TUERP) vs the conventional bipolar
      transurethral resection of the prostate (B-TURP) for the treatment of prostates
      larger than 80 mL. METHODS: From April 2012 to May 2014, 86 patients with a
      prostate volume of >80 mL were divided into 2 groups to undergo M-TUERP and B
      TURP. In the M-TUERP group, we proposed combining the 12-mm trocar suprapubic
      cystostomy and using the techniques of "umbrella-shaped resection," "point
      resection," and "segmental enucleation" to modify the transurethral enucleation
      and resection of the prostate procedure. The perioperative clinical data were
      recorded and analyzed. RESULTS: There were no significant differences in
      preoperative characteristics between the 2 groups. Both groups were similar with
      the operative time. The M-TUERP group was significantly superior to the B-TURP
      group in terms of the weight of the resected tissue, the mean intraoperative
      bladder pressure, hemoglobin decrease, bladder irrigation duration, and urethral
      catheterization time. No transurethral resection syndrome and incontinence
      occurred in either group. Compared with the B-TURP group, none of the patients in
      the M-TUERP group suffered blood transfusion, clot retention, recatheterization,
      dysuria and reoperation. At the 3-year follow-up, patients who underwent M-TUERP
      had better international prostate symptom scores, maximum urinary flow rates, and
      quality of life scores. CONCLUSION: Our modification of the transurethral
      enucleation and resection of the prostate procedure is a safe and effective
      method for the surgical treatment of large-volume benign prostatic hyperplasia.
      It can simplify the surgical procedures, reduce complications, lower difficulties
      and shorten the learning curve. At 3-year follow-up, the M-TUERP shows a superior
      and durable clinical outcome than the B-TURP.

PMID- 29203185
TI  - Conservative Management of High-grade Renal Trauma Does Not Lead to Prolonged
      Hospital Stay.
AB  - OBJECTIVE: To evaluate the effect of conservative management of high-grade renal
      trauma on length of hospitalization, we aim to describe characteristics of
      patients with high-grade renal trauma that are associated with an increased
      length of stay (LOS) and the effect of conservative vs surgical management on
      hospital LOS. METHODS: A retrospective review of all patients who suffered
      unilateral high-grade renal trauma (grade 3 or higher) from September 1977 to
      August 2012 at San Francisco General Hospital in San Francisco, CA was performed.
      Patients' demographic information, mechanism of injury, injury grade, data about
      associated injuries, hospital LOS, and management were collected. Descriptive
      analysis was performed using chi-square, ordered logistic regression, and linear
      regression analysis. Multivariable analysis was performed using a Fine-Gray model
      of competing risks survival analysis, adjusting for trauma type, grade, surgery,
      associated injury, and complications. RESULTS: The cohort consisted of 408
      patients with high-grade unilateral renal trauma of which 257 patients underwent
      renal exploration. The adjusted multivariable analysis revealed that trauma type,
      injury grades, nongenitourinary surgery, associated injuries, and complications
      were associated with increased hospital LOS (P <.01 for all). Renal exploration
      compared to conservative management for high-grade renal trauma was not
      associated with an increased hospital LOS (P = .10). CONCLUSION: There is no
      significant difference between conservative and surgical management of high-grade
      renal trauma in terms of hospital LOS. Conservative management of high-grade
      renal trauma does not impact patients' length of hospitalization.

PMID- 29203186
TI  - Direction of Rotation in Testicular Torsion and Identification of Predictors of
      Testicular Salvage.
AB  - OBJECTIVES: To identify the rate at which testicular torsion occurs in a lateral
      direction and identify any predictors of direction of testicular rotation and
      orchiectomy. MATERIALS AND METHODS: We performed a retrospective review of 104
      cases of emergent scrotal exploration performed for testicular torsion by 3
      pediatric urologists from 2003 to 2017. Patients with neonatal torsion, negative
      scrotal exploration, or exploration for presumed intermittent testicular torsion
      were excluded. Univariable logistic regression was performed to assess if any
      factors predicted direction of testicular rotation. Univariable and multivariable
      logistic regression was used to identify predictors of testicular salvage.
      RESULTS: Of 104 cases of acute testicular torsion, information regarding the
      direction of testicular rotation was available in 81 patients. Lateral testicular
      rotation occurred in 38 cases (46%). No factors were found to be predictive of
      direction of torsion. Orchiectomy for testicular nonviability was performed in 50
      of 104 cases (48%). On univariable analysis, younger age (p = .002), absence of
      gastrointestinal symptoms (P = .02), time to exploration (P < .001), testicular
      size differential on ultrasound (p = .002), absence of hydrocele (P = .01),
      abnormal ultrasound echotexture (P < .001), and degree of torsion (P = .04) were
      associated with orchiectomy. With the exception of absence of gastrointestinal
      symptoms, all predictors of orchiectomy remained statistically significant on
      multivariable analysis. CONCLUSION: Testicular rotation occurs in a lateral
      direction in 46% of cases. Lateral manual detorsion should be performed only with
      awareness of the potential for increasing the degree of testicular rotation. New
      independent predictors of testicular salvage were identified.

PMID- 29203187
TI  - Paratesticular Liposarcoma Masquerading as an Inguinal Hernia.
AB  - A man with left scrotal swelling felt to represent inguinal hernia underwent
      computed tomography scan for reported bleeding after prostate biopsy. Computed
      tomography scan revealed a 15-cm extratesticular left scrotal mass containing
      both fat and soft tissue components, raising concern for dedifferentiated
      liposarcoma. At surgery and pathology, the mass was separate from the left
      testis, epididymis, and spermatic cord. Histopathologic findings were consistent
      with paratesticular dedifferentiated liposarcoma.

PMID- 29203188
TI  - Congenital Segmental Megaureter in an Ectopic Kidney.
AB  - We describe the imaging findings of a 19-year-old female patient who presented
      with recurrent urinary tract infections and pain abdomen which was diagnosed to
      be due to a left-sided focal segmental megaureter with a calculus. The highlights
      of the case are functioning moiety with no other associated anomalies like
      vesicoureteral reflux, Duplex system, and so on.

PMID- 29203189
TI  - Inhibition of Jun N-terminal Kinase Improves Erectile Function by Alleviation of
      Cavernosal Apoptosis in a Rat Model of Cavernous Nerve Injury.
AB  - OBJECTIVE: To determine whether Jun N-terminal kinase (JNK) inhibition could
      alleviate erectile dysfunction (ED) through suppressing cavernosal apoptosis in a
      rat model of carvernosal nerve crush injury (CNCI), thereby providing potential
      therapeutic strategy for alleviating postradical prostatectomy ED. MATERIALS AND
      METHODS: Fifty-six 11-week-old male Sprague-Dawley rats were categorized equally
      into the following 4 groups: (1) sham surgery (S), (2) CNCI (I), (3) CNCI treated
      with low-dose JNK inhibitor (L), and (4) CNCI treated with high-dose JNK
      inhibitor (H). The L and H groups received daily intraperitoneal injection of JNK
      inhibitors (1.0 mg/kg for the L group and 10.0 mg/kg for the H group) for 2 weeks
      starting from the following day after surgery. Erectile response, Western blot,
      and immunohistochemistry were assessed. RESULTS: At 2 weeks after surgery,
      intracavernous pressure-mean arterial pressure and area under the curve-mean
      arterial pressure in group I were significantly decreased compared with those in
      group S. Erectile responses in group H were significantly improved compared with
      those in group I. Group I showed decreased smooth muscle (SM) content, increased
      apoptosis, increased apoptotic or SM cells positive for phosphorylated c-Jun,
      increased c-Jun phosphorylation, and decreased Bcl2-to-Bax ratio compared with
      group S. Group H showed significant improvements in histologic alterations and
      dysregulation of the JNK-driven pathway. CONCLUSION: Our data suggest that JNK
      inhibition can improve erectile function by alleviating cavernosal apoptosis
      through restoring the JNK-related pathway toward normal. Thus, an early
      therapeutic strategy targeting the JNK pathway might be able to alleviate
      cavernosal SM apoptosis and postradical prostatectomy ED caused by cavernous
      nerve injury.

PMID- 29203190
TI  - Organ Preservation for Recurrent Urethral Adenocarcinoma With Concurrent
      Chemotherapy and Radiation.
AB  - Urethral adenocarcinoma of males is a rare disease with limited prospective data
      to define optimal treatment. Surgical excision remains the primary treatment for
      early-stage disease. Multimodality therapy with a combination of chemotherapy,
      radiation, or surgery has been explored in patients with locally advanced
      disease. We present the case of a 45-year-old-man with a locally recurrent
      urethral adenocarcinoma after initial surgical resection managed successfully
      with combined weekly cisplatinum and radiation therapy.

PMID- 29203191
TI  - A Simple Neobladder Using a Porcine Model: The Double Limb U-Pouch.
AB  - OBJECTIVE: To create a simple neobladder and determine whether the double-limb U
      Pouch (D-LUP) has the same capacity and compliance as a Studer or Camey I
      neobladder. To develop an orthotopic diversion that can be applied to robotic
      surgery with laboratory data supporting the concept. MATERIALS AND METHODS:
      Kidneys, ureters, bladders, and small intestine were obtained from pigs at the
      time of scheduled autopsy after completion of institutionally approved
      investigational trauma protocols. A Camey I neobladder, spherical neobladder, and
      D-LUP, were constructed from 40-cm segments of small intestine. They were
      compared for capacity, compliance, and pouch-to-urethra anastomotic distance.
      RESULTS: The cystometric capacity at 30 cm H2O for the Camey I, Studer, and D-LUP
      neobladders were 250 mL, 350 mL, and 430 mL, respectively. The pouch-to-urethra
      anastomotic distance was 0 cm for the Camey I, 10 cm for the spherical reservoir,
      and 0 cm for the D-LUP. Compliance was 10 mL/cm H20 for the Camey 1, 15 mL/cm H2O
      for the sphere, and 16 mL/cm H20 for the D-LUP. CONCLUSION: The D-LUP neobladder
      was simple to construct, had a more dependent ileo-urethrostomy site, larger
      capacity, and similar compliance when compared with a spherical neobladder.

PMID- 29203192
TI  - Herd-Level Monitoring and Prevention of Displaced Abomasum in Dairy Cattle.
AB  - Displaced abomasum (DA) is a postpartum disease that causes significant economic
      losses in the dairy industry. Abomasal atony and excessive production of gas have
      been reported as prerequisites for the development of DA. The exact cause of DA
      is unknown, yet infectious and metabolic disease, diet composition and physical
      form, cow comfort, and management of dairy cows during the transition period have
      been associated with the occurrence of this disorder. This review article
      discusses different factors that lead to the development of DA and strategies for
      monitoring DA and its comorbidities at the herd level.

PMID- 29203193
TI  - Fructose-1,6-bisphosphatase deficiency as a cause of recurrent hypoglycemia and
      metabolic acidosis: Clinical and molecular findings in Malaysian patients.
AB  - BACKGROUND: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal
      recessive inborn error of gluconeogenesis. We reported the clinical findings and
      molecular genetic data in seven Malaysian patients with FBPase deficiency.
      METHODS: All patients diagnosed with FBPase deficiency from 2010 to 2015 were
      included in this study. Their clinical and laboratory data were collected
      retrospectively. RESULTS: All the patients presented with recurrent episodes of
      hypoglycemia, metabolic acidosis, hyperlactacidemia and hepatomegaly. All of them
      had the first metabolic decompensation prior to 2 years old. The common
      triggering factors were vomiting and infection. Biallelic mutations in FBP1 gene
      (MIM*611570) were identified in all seven patients confirming the diagnosis of
      FBPase deficiency. In four patients, genetic study was prompted by detection of
      glycerol or glycerol-3-phosphate in urine organic acids analysis. One patient
      also had pseudo-hypertriglyceridemia. Seven different mutations were identified
      in FBP1, among them four mutations were new: three point deletions (c.392delT,
      c.603delG and c.704delC) and one splice site mutation (c.568-2A > C). All four
      new mutations were predicted to be damaging by in silico analysis. One patient
      presented in the neonatal period and succumbed due to sepsis and multi-organ
      failure. Among six survivors (current age ranged from 4 to 27 years), four have
      normal growth and cognitive development. One patient had short stature and
      another had neurological deficit following status epilepticus due to profound
      hypoglycemia. CONCLUSION: FBPase deficiency needs to be considered in any
      children with recurrent hypoglycemia and metabolic acidosis. Our study expands
      the spectrum of FBP1 gene mutations.

PMID- 29203194
TI  - Hepatoblastoma in an extremely low birth-weight infant with Beckwith-Wiedemann
      syndrome.

PMID- 29203195
TI  - 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients
      on Oral Anticoagulants: A Report of the American College of Cardiology Task Force
      on Expert Consensus Decision Pathways.

PMID- 29203196
TI  - Hepatorenal protective effects of medicinal herbs in An-Gong-Niu-Huang Wan (AGNH)
      against cinnabar- and realgar-induced oxidative stress and inflammatory damage in
      mice.
AB  - An-Gong-Niu-Huang Wan (AGNH) is a famous traditional Chinese medicine
      prescription that contains cinnabar (HgS) and realgar (As2S2); the clinical
      practice of AGNH is hindered because both mercury and arsenic are hepatorenal
      toxic metalloids. It is noted that the cinnabar and realgar in AGNH are not used
      alone, but rather combined with different kinds of medicinal herbs as a formula
      to use. In this study, we evaluated the hepatorenal protective effects of the
      medicinal herbs in AGNH after co-exposure to cinnabar and realgar for 4 weeks in
      mice. The combination of the herbs in AGNH alleviated cinnabar and realgar
      induced histopathological alterations and oxidative stress in the liver and
      kidneys. Furthermore, in cinnabar and realgar-treated mice, the increased
      expression levels of inducible enzymes (COX-2 and iNOS) and proinflammatory
      mediators (IL-1beta, TNF-alpha, PGE2 and NO) in the liver and kidneys were
      consistently down-regulated when medicinal herbs were combined as a formula. We
      also found that the herbs could reduce the inflammatory response by the
      inactivation of the MAPK and PI3K/Akt signaling pathway and the resulting
      blockade of NF-kappaB activation. Overall, our data indicates that the herbal
      medicines in AGNH attenuate cinnabar and realgar-induced hepatorenal toxicity by
      improving antioxidant competence and suppressing inflammatory injury.

PMID- 29203197
TI  - Safety evaluation of dietary levels of 25-hydroxyvitamin D3 in growing calves.
AB  - The objective of this study was to evaluate the safety of 25-OH-D3 addition to
      the diet of bovine calves. The investigation was conducted as a feeding
      experiment for 90 days. 40 calves were allotted to four groups: T1 - control
      group which received 30 IU vitamin D3/kg feed, and three experimental groups,
      which received 25-OH-D3 in increasing dosages: T2 - 25-OH-D3 at 1.7 MUg/kg, T3 -
      25-OH-D3 at 5.1 MUg/kg and T4 - 25-OH-D3 at 8.5 MUg/kg. All calves in the four
      groups gained weight continually: no growth depression was observed. No adverse
      effects of 25- OH-D3 were observed for any of the hematology and serum chemistry
      parameters measured or during the routine clinical examinations. Plasma 25-OH-D3
      concentration was higher (p<0.05) in groups T2, T3 and T4 compared to that
      observed in group T1. Tissues content of 25-OH-D3 was significantly higher in in
      groups T2, T3 and T4 than in group T1. In the post-mortem evaluation, no adverse
      effects of the different 25-OH-D3 doses were observed, neither during the gross
      pathology nor in the histological examination. The results of this study show
      explicitly that there were no adverse effects of 25-OH-D3 compared to the control
      group, supplemented with vitamin D3.

PMID- 29203198
TI  - Phylogeny and expression patterns of two apolipoprotein E genes in the flatfish
      Senegalese sole.
AB  - The apolipoprotein E (ApoE) is a key component of several lipoproteins involved
      in lipid homeostasis. In this study, two cDNA sequences encoding ApoE (referred
      to as apoEa and apoEb) were characterized in the flatfish Solea senegalensis. The
      predicted peptides contained conserved structural blocks related with their
      capacity for lipid binding and lipoprotein receptor interaction. At genomic
      level, both genes contained five exons and four introns and they were organized
      into two tandem arrays with apoA-IV gene copies. The phylogenetic analysis
      clearly separated them into two well-supported clusters that matched with their
      organization in the genome of teleosts. Whole-mount in situ hybridization located
      the apoEa signal in the yolk syncytial layer (YSL) of lecitothrophic larval
      stages (0dph) and in the anterior intestine of exotrophic larvae and benthic
      fish. In the case of apoEb, hybridization signals were located in the YSL, tail
      bud, eyes and mouth at 0dph and in the otic vesicle, hindbrain, eyes, pharynx,
      mouth, heart and intestine at 1dph. In exotrophic larvae, apoEb was ubiquitously
      expressed in several tissues such as taste buds, brain, mouth, nostril, gills,
      intestine, liver and around the neuromasts and eyes. Quantification of mRNA
      levels in pools of whole larvae confirmed distinct expression patterns with a
      significant reduction of apoEa and an increase of apoEb mRNA levels throughout
      larval development. Moreover, only apoEa transcripts increased in response to
      food supply suggesting that this paralog mostly participates in the absorption
      and transport of dietary lipids and the apoEb in the redistribution of endogenous
      lipids as well as in neural tissue regeneration.

PMID- 29203199
TI  - Overexpression of OCT4 induced by modulation of histone marks plays crucial role
      in breast cancer progression.
AB  - OCT4 is known as the gatekeeper of pluripotent embryonic state as it is
      responsible for maintenance of pluripotency via self-renewal of embryonic stem
      cells and acquisition of induced pluripotency via somatic cell reprogramming.
      OCT4 is responsible for oncogenic transformation by disrupting pre-scheduled
      differentiation programs and in general, favoring evolution of cancer cells into
      a more aggressive cancer stem cell phenotype. In this study, we have investigated
      in details, the epigenetic regulatory mechanisms responsible for over-expression
      and subsequent aberrant function of OCT4 in breast cancer. Expression of OCT4 in
      breast cancer tissues and cell lines was determined by qRT-PCR, Western blot,
      immunohistochemistry and immunocytochemistry followed by investigation of pro
      tumorigenic properties such as cell proliferation, migration and apoptosis by
      gene knockdown and treatment with epigenetic modulators. Ectopic treatment of
      epigenetic modulators was done followed by MS-PCR and chromatin
      immunoprecipitation. OCT4 is over-expressed in both of the breast cancer cell
      lines; MCF7 and MDA-MB-231 and its inhibition resulted in drastic decrease in
      rate of cell proliferation, metastatic ability and induced apoptosis. After
      treatment with epigenetic modulators, general increase in expression of OCT4 was
      observed at both gene and protein levels; however, changes of promoter DNA
      methylation was not found to be significant during OCT4 over-expression. Active
      histone marks especially H3K4me3 and H3K9acS10p were enriched in the promoter
      region with very low levels of repressive marks H3K9me3 and H3K27me3 indicating
      that active histone modifications are the deciding factor in inducing over
      expression of OCT4 during breast carcinogenesis. These findings could provide the
      basis on which epigenetic therapy, targeting reversible epigenetic modifications
      and their perpetuating enzymes, can be designed for effective treatment of
      aggressive breast cancer.

PMID- 29203200
TI  - Traumatic skull fractures in children and adolescents: A retrospective
      observational study.
AB  - OBJECTIVE: To investigate the epidemiological features of child and adolescent
      (<=18 years old) patients managed for traumatic skull fractures (TSKFs) and
      associated traumatic brain injury (TBI). DESIGN: 393 Patients who were children
      and adolescent who had TSKFs admitted to our university affiliated hospitals
      between January 2003 and December 2010. The incidence and patterns were
      summarized with respect to different age group, admission time and etiology.
      SETTING: Two university-affiliated hospitals from January 2003 to May 2010.
      RESULTS: The most common etiologies were motor vehicle collisions (MVCs) (166,
      42.2%) and high fall (101, 25.7%). The most common skull fracture sites were
      parietal fractures (n=111, 28.2%) and basilar skull fracture (n=111, 28.2%). A
      total of 300 (76.3%) patients suffered TBI and 23 (5.9%) patients suffered OCI.
      The most common intracranial hemorrhage was epidural hemorrhage (n=94, 23.9%).
      The frequencies of emergency admission, medical insurance and associated injuries
      were 56.2% (n=221), 22.4% (n=88) and 37.2% (n=146). The frequencies of TBI and
      associated injuries were significantly increased from 53.45% to 76.3% and from
      6.9% to 41.6% with age, respectively. CONCLUSIONS: MVCs were the most common
      etiologies. Parietal and basilar skull fractures, epidural hemorrhages were the
      most common fracture sites and intracranial hemorrhage.

PMID- 29203201
TI  - Combat-related acetabular fractures: Outcomes of open versus closed injuries.
AB  - INTRODUCTION: Since the onset of the Global War on Terror close to 50,000 United
      States service members have been injured in combat, many of these injuries would
      have previously been fatal. Among these injuries, open acetabular fractures are
      at an increased number due to the high percentage of penetrating injuries such as
      high velocity gunshot wounds and blast injuries. These injuries lead to a greater
      degree of contamination, and more severe associated injuries. There is a
      significantly smaller proportion of the classic blunt trauma mechanism typically
      seen in civilian trauma. METHODS: We performed a retrospective review of the
      Department of Defense Trauma Registry into which all US combat-injured patients
      are enrolled, as well as reviewed local patient medical records, and radiologic
      studies from March 2003 to April 2012. Eighty seven (87) acetabular fractures
      were identified with 32 classified as open fractures. Information regarding
      mechanism of injury, fracture pattern, transfusion requirements, Injury Severity
      Score (ISS), and presence of lower extremity amputations was analyzed. RESULTS:
      The mechanism of injury was an explosive device in 59% (n=19) of patients with an
      open acetabular fracture; the remaining 40% (n=13) were secondary to ballistic
      injury. In contrast, in the closed acetabular fracture cohort 38% (21/55) of
      fractures were due to explosive devices, and all remaining (n=34) were secondary
      to blunt trauma such as falls, motor vehicle collisions, or aircraft crashes.
      Patients with open acetabular fractures required a median of 17units of PRBC
      within the first 24h after injury. The mean ISS was 32 in the open group compared
      with 22 in the closed group (p=0.003). In the open fracture group nine patients
      (28%) sustained bilateral lower extremity amputations, and 10 patients (31%)
      ultimately underwent a hip disarticulation or hemi-pelvectomy as their final
      amputation level. DISCUSSION: Open acetabular fractures represent a significant
      challenge in the management of combat-related injuries. High ISS and massive
      transfusion requirements are common in these injuries. This is one of the largest
      series reported of open acetabular fractures. Open acetabular fractures require
      immediate damage control surgery and resuscitation as well as prolonged
      rehabilitation due to their severity. The dramatic number of open acetabular
      fractures (37%) in this review highlights the challenge in treatment of combat
      related acetabular fractures.

PMID- 29203202
TI  - Does it fit? - Impaired affordance perception after stroke.
AB  - Affordance perception comprises the evaluation of whether our given bodily
      capabilities and properties of the environment allow particular actions. Typical
      impairments after left brain damage in motor cognition as well as after right
      brain damage in visuo-spatial abilities may affect the evaluation of whether
      interactions with objects are possible. Further it is unclear whether deficient
      motor function is accounted for when deciding upon action opportunities. For
      these purposes we developed a paradigm with two tasks that differ in their type
      of demands on affordance perception and tested it in healthy young adults
      (Randerath and Frey, 2016). Here, we applied one of these two tasks in stroke
      patients and age matched healthy participants. A sample of 34 stroke patients
      with either left (LBD) or right brain damage (RBD) and 29 healthy controls made
      decisions about whether their hands would fit through a defined horizontal
      aperture presented in various sizes, while they remained still. Data was analyzed
      using a detection theory approach and included criterion, perceptual sensitivity
      and diagnostic accuracy as dependent variables. In addition we applied modern
      voxel based lesion analyses to explore neural correlates. Compared to controls,
      both patient groups demonstrated lower perceptual sensitivity. As predicted,
      increased motor cognitive deficiencies after left brain damage and visuo-spatial
      deficits after right brain damage were associated with worse performance.
      Preliminary lesion analyses demonstrated that next to lesions in ventro-dorsal
      regions, damage in the cortex-claustrum-cingulate pathway may affect perceptual
      sensitivity. Results were similar for left and right brain damage suggesting a
      bilateral network. Accordingly, we propose that perceptual sensitivity for
      affordance based judgments is a capability depending on motor-cognitive and visuo
      spatial processing, which frequently is deficient after left or right brain
      damage, respectively. Further research on diagnostics and training in affordance
      perception after brain damage is needed.

PMID- 29203203
TI  - A new insight into sentence comprehension: The impact of word associations in
      sentence processing as shown by invasive EEG recording.
AB  - The effect of word association on sentence processing is still a matter of
      debate. Some studies observe no effect while others found a dependency on
      sentence congruity or an independent effect. In an attempt to separate the
      effects of sentence congruity and word association in the spatio-temporal domain,
      we jointly recorded scalp- and invasive-EEG (iEEG). The latter provides highly
      localized spatial (unlike scalp-EEG) and high temporal (unlike fMRI) resolutions.
      We recorded scalp- and iEEG in three patients with refractory epilepsy. The
      stimuli consisted of 280 sentences with crossed factors of sentence congruity and
      within sentence word-association. We mapped semantic retrieval processes involved
      in sentence comprehension onto the left temporal cortex and both hippocampi, and
      showed for the first time that certain localized regions participate in the
      processing of word-association in sentence context. Furthermore, simultaneous
      recording of scalp- and iEEG gave us a direct overview of signal change due to
      its propagation across the head tissues.

PMID- 29203204
TI  - Component deficits of visual neglect: "Magnetic" attraction of attention vs.
      impaired spatial working memory.
AB  - Visual neglect is a disabling consequence of right hemisphere damage, whereby
      patients fail to detect left-sided objects. Its precise mechanisms are debated,
      but there is some consensus that distinct component deficits may variously
      associate and interact in different patients. Here we used a touch-screen based
      procedure to study two putative component deficits of neglect, rightward
      "magnetic" attraction of attention and impaired spatial working memory, in a
      group of 47 right brain-damaged patients, of whom 33 had signs of left neglect.
      Patients performed a visual search task on three distinct conditions, whereby
      touched targets could (1) be tagged, (2) disappear or (3) show no change.
      Magnetic attraction of attention was defined as more left neglect on the tag
      condition than on the disappear condition, where right-sided disappeared targets
      could not capture patients' attention. Impaired spatial working memory should
      instead produce more neglect on the no change condition, where no external cue
      indicated that a target had already been explored, than on the tag condition.
      Using a specifically developed analysis algorithm, we identified significant
      differences of performance between the critical conditions. Neglect patients as a
      group performed better on the disappear condition than on the no change condition
      and also better in the tag condition comparing with the no change condition. No
      difference was found between the tag condition and the disappear condition. Some
      of our neglect patients had dissociated patterns of performance, with predominant
      magnetic attraction or impaired spatial working memory. Anatomical results issued
      from both grey matter analysis and fiber tracking were consistent with the
      typical patterns of fronto-parietal and occipito-frontal disconnection in
      neglect, but did not identify lesional patterns specifically associated with one
      or another deficit, thus suggesting the possible co-localization of attentional
      and working memory processes in fronto-parietal networks. These findings give
      support to the hypothesis of the co-occurrence of distinct cognitive deficits in
      visual neglect and stress the necessity of multi-component models of visuospatial
      disorders.

PMID- 29203205
TI  - Effects of intentionality and subliminal information in free-choices to inhibit.
AB  - Stopping an action at the very last moment is an important feature of human
      behavioural flexibility. Intentional inhibition has been defined as the ability
      to inhibit an action on the basis of an internal decision process. Without this
      ability, actions would be impulsive and would leave little space to correct
      misguided decisions. Previous research suggests that making a choice between
      action alternatives activates a specific "choice network" that includes the
      rostral cingulate zone (RCZ), the anterior insula (AI), the dorsolateral
      prefrontal cortex (DLPFC) and the inferior parietal lobe (IPL). The activity of
      this network has shown to be influenced by non-conscious (subliminal) stimuli. In
      this study, we tested whether the same regions are recruited by free-choices to
      inhibit and modulated by unconscious information as reported in the case of free
      choices to act. Using functional magnetic resonance imaging (fMRI) we manipulated
      the degree of 'freedom' of the choice between acting and inhibiting an action by
      introducing explicit cues or leaving the participants free to choose between
      action alternatives. We included subliminal masked primes to test whether
      responses to targets were facilitated and/or obstructed by conditions of
      congruency and incongruency between primes and targets. Our findings confirmed
      higher activation of the "choice network" in free-choice trials when compared to
      cued choices. However subliminal priming failed to significantly influence
      participants' responses, in free-choice conditions.

PMID- 29203206
TI  - Expression of hypothalamic kisspeptin, neurokinin B, and dynorphin A neurons
      attenuates in female Zucker fatty rats.
AB  - Zucker fatty (ZF) rats are considered to be an obese model due to leptin receptor
      abnormality and such rats show infertility. Pulsatile gonadotropin-releasing
      hormone/luteinizing hormone (LH) secretion, which is important for follicular
      development in females, is considered to be controlled by KNDy neurons
      coexpressing kisspeptin, neurokinin B (NKB), and dynorphin A (DynA), encoded by
      Kiss1, Tac3, and Pdyn, respectively, in the hypothalamic arcuate nucleus (ARC).
      The purpose of this study is to examine the expression of KNDy neurons in female
      ZF rats by histochemical approach because pulsatile LH secretion is suppressed.
      Zucker lean (ZL) rats served as a control group. Animals were ovariectomized and
      subcutaneously implanted with a silicon tube containing estradiol to produce
      plasma level of estradiol during diestrus. Plasma LH levels decreased in ZF rats
      compared with ZL rats. The expressions of each mRNA (Kiss1, Tac3, and Pdyn) and
      each peptide (kisspeptin, NKB, and DynA) in the ARC significantly decreased in ZF
      rats compared with ZL rats. However, the number of Kiss1 neurons in the anterior
      ventral periventricular nucleus did not significantly differ between the two
      groups. These results suggest that dysfunction of leptin signaling negatively
      affects KNDy neurons in the ARC, resulting in reproductive dysfunction caused by
      suppression of the LH pulse.

PMID- 29203207
TI  - Suppression of autophagy in the brain of transgenic mice with overexpression of
      A53T-mutant alpha-synuclein as an early event at synucleinopathy progression.
AB  - Transgenic overexpression of alpha-synuclein is a common model of Parkinson's
      disease (PD). Accumulation of A53T-mutant alpha-synuclein induces three autophagy
      cell responses: the inhibition of autophagy caused by the accumulation of alpha
      synuclein, compensatory activation of macroautophagy in response to inhibition of
      the chaperone-mediated autophagy, and toxic effects of mutant alpha-synuclein
      accompanied by the activation of autophagy. The overall effect of long-term
      overexpression of mutant alpha-synuclein in vivo remains unclear. Here we
      evaluated the activity of autophagy in the frontal cortex, striatum and s.nigra
      of transgenic mice with overexpression of A53T-mutant alpha-synuclein. We
      revealed low autophagic activity in the dopaminergic structures of 5 mo.
      transgenic B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J mice as compared to controls C57Bl/6J
      mice. The results were further supported by the data on tyrosine hydroxylase
      immunostaining that indicated its significant decrease in the striatum but not in
      s.nigra of transgenic mice and might be more related to earlier damage of
      dopaminergic neurites than to the somas due to disturbed formation of
      autophagosomes at the neuron periphery. The results provide evidence of a
      possible contribution of suppressed autophagy to the development of PD-like
      condition as an early event at synucleinopathy progression. Activation of
      autophagy at early stages of PD seems to be a promising therapeutic tool while
      B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J mice are suggested as a suitable and adequate
      model for studying the neuroprotective potential and value of this approach.

PMID- 29203208
TI  - Systems consolidation revisited, but not revised: The promise and limits of
      optogenetics in the study of memory.
AB  - Episodic memories (in humans) and event-like memories (in non-human animals)
      require the hippocampus for some time after acquisition, but at remote points
      seem to depend more on cortical areas instead. Systems consolidation refers to
      the process that promotes this reorganization of memory. Various theoretical
      frameworks accounting for this process have been proposed, but clear evidence
      favoring one or another of these positions has been lacking. Addressing this
      issue, a recent study deployed some of the most advanced neurobiological
      technologies - optogenetics and calcium imaging - and provided high resolution,
      precise observations regarding brain systems involved in recent and remote
      contextual fear memories. We critically review these findings within their
      historical context and conclude that they do not resolve the debate concerning
      systems consolidation. This is because the relevant question concerning the
      quality of memory at recent and remote time points has not been answered: Does
      the memory reorganization taking place during systems consolidation result in
      changes to the content of memory?

PMID- 29203209
TI  - Comparative efficacy of two paclitaxel-coated balloons with different excipient
      coatings in patients with coronary in-stent restenosis: A pooled analysis of the
      Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug
      Eluting Stent In-Stent Restenosis 3 and 4 (ISAR-DESIRE 3 and ISAR-DESIRE 4)
      trials.
AB  - BACKGROUND: Angioplasty with paclitaxel-coated balloons (PCB) is recommended for
      treatment of patients with coronary in-stent restenosis (ISR) according to
      European clinical practice guidelines. Most clinical trials have investigated
      iopromide-based PCB and there is a paucity of data comparing efficacy against
      butyryl-tri-hexyl citrate (BTHC)-based PCB. Our aim was to compare the
      performance of two widely-used PCB in the treatment of coronary ISR. METHODS: We
      analysed patients treated with BTHC- or iopromide-PCB for treatment of drug
      eluting stent ISR in the setting of 2 consecutive trials with identical inclusion
      and exclusion criteria. The primary endpoint was diameter stenosis at 6-8month
      angiographic surveillance. The secondary endpoint of interest was the composite
      of death, myocardial infarction (MI) or target-lesion revascularisation (TLR) at
      1year. Multivariate analysis was performed to adjust for differences in baseline
      characteristics between groups. RESULTS: In total, 264 patients were treated with
      BTHC-PCB (n=127) or iopromide-PCB (n=137). Baseline patient characteristics were
      similar for both groups. Post-procedure stenosis was slightly larger with BTHC
      PCB (22.3 [SD 8.2]% vs. 18.4 [SD 9.9]%, P=0.001). At 6-8month angiography,
      diameter stenosis was 40.4 [SD 21.9]% vs. 37.4 [SD 21.4]% in the BTHC-PCB and
      iopromide-PCB groups, respectively (P=0.16, Padjusted=0.32). At 1year, death, MI
      or TLR occurred in 29 (23.2%) vs. 32 (23.4%) patients in the BTHC-PCB and
      iopromide-PCB groups, respectively (HR 1.03 [95% CI 0.62-1.70], P=0.91,
      Padjusted=0.96). CONCLUSIONS: In patients undergoing intervention for ISR,
      angioplasty with BTHC-PCB showed similar angiographic and clinical results at
      1year compared with iopromide-PCB.

PMID- 29203210
TI  - Indoxyl sulfate upregulates the cannabinoid type 1 receptor gene via an ATF3/c
      Jun complex-mediated signaling pathway in the model of uremic cardiomyopathy.
AB  - BACKGROUND: The risk of cardiovascular disease is notably increased in patients
      with chronic kidney disease (CKD) and cannabinoid receptor type 1 (CB1R) plays an
      important role in the development of uremic cardiomyopathy. However, the
      molecular mechanism underlying the uremic toxin-induced upregulation of CB1R
      remains elusive. METHODS: The expression of the ATF3/c-Jun complex and CB1R in
      both in vivo and in vitro models of CKD were measured. We also determined the
      impact of the ATF3/c-Jun complex on CB1R expression by transfecting H9c2 cells
      with dominant negative mutants of ATF3 or c-Jun. Inhibitors of organic anion
      transport, specific MAPK pathways and oxidative DNA damage were also used to
      assess the pathways mediating the effects of indoxyl sulfate (IS). RESULTS: CB1R
      upregulation was associated with increased ATF3 expression and c-Jun
      phosphorylation in CKD both in vivo and in vitro. Expression of dominant-negative
      ATF3 or c-Jun mutants in IS-treated cells significantly reduced CB1R mRNA levels.
      Moreover, Co-IP revealed that the ATF3/c-Jun complex is formed and ChIP confirmed
      its binding to the CB1R promoter, suggesting that this complex directly
      stimulates CB1R transcription in CKD. Blocking the cellular entry of IS using an
      organic anion transport inhibitor, as well as inhibiting the ERK1/2 and/or JNK
      pathways, abrogated the effects of IS on CB1R, ATF3, and c-Jun expression. The IS
      induced reactive oxygen species (ROS) was observed in the mitochondria.
      CONCLUSIONS: We demonstrate that uremic toxins induce ATF3/c-Jun complex-mediated
      CB1R expression both in vivo and in vitro, possibly by modulating the ERK1/2 and
      JNK signaling pathways and ROS.

PMID- 29203211
TI  - QTc interval, cardiovascular events and mortality in patients with atrial
      fibrillation.
AB  - BACKGROUND: A longer QTc interval has been associated with more adverse
      cardiovascular events and death in the general population. Little evidence is
      available on these relationships among patients with atrial fibrillation (AF).
      METHODS: We performed a prospective observational multicenter cohort study of
      1413 patients with AF. A resting 12-lead electrocardiogram (ECG) was performed at
      baseline. QT interval was corrected for heart rate using the Bazett formula
      (QTc). Endpoints for this study included hospitalizations for congestive heart
      failure (CHF), a combination of cardiovascular death, myocardial infarction,
      stroke, systemic arterial embolism (MACE) and all-cause mortality. RESULTS: Mean
      age of our population was 68+/-12years and 420 (30%) participants were female.
      Median QTc was 432ms (interquartile range 409; 457). The mean follow-up time was
      3.6+/-1.5years. After multivariable adjustment, there was a linear increase in
      risk with increasing QTc interval for incident CHF (hazard ratio (HR) per 1-SD
      increase in QTc 1.3 [95% CI 1.1; 1.6], p=0.008), MACE (HR 1.2 [1.0; 1.4], p=0.02)
      and all-cause mortality (HR 1.3 [1.0; 1.6], p=0.002). Results were consistent
      whether or not patients were in sinus rhythm on the baseline ECG (HR for CHF 1.7
      versus 1.3, p interaction 0.08; HR for MACE 1.3 versus 1.2, p interaction 0.9; HR
      for all-cause mortality 1.4 versus 1.4, p interaction 0.9). CONCLUSIONS: In this
      large well-characterized cohort of AF patients, QTc interval was independently
      associated with adverse outcomes. These results were independent of the rhythm on
      the baseline ECG.

PMID- 29203213
TI  - Examining the role of extracorporeal membrane oxygenation in patients following
      suspected or confirmed suicide attempts: A case series.
AB  - The decision to offer extracorporeal membrane oxygenation (ECMO) is based on a
      risk/benefit assessment and the likelihood of a treatable underlying condition or
      the feasibility of destination therapy (durable mechanical support or thoracic
      organ transplantation) should heart-lung function fail to improve. Patients who
      present following suspected suicide attempts who fail medical therapy may pose a
      dilemma for clinicians. An assessment to determine if a patient has a high
      likelihood of psychiatric recovery such that bridging with ECMO or ultimately
      destination therapy could or should be offered is not always feasible in the
      setting of critical illness. This case series reviews our institution's
      experience with ECMO in the management of five patients who presented following
      suspected or confirmed suicide attempts. All five patients survived to hospital
      discharge. Two had subsequent psychiatric admissions, one following a repeat
      suicide attempt. A discussion of these cases demonstrates the effectiveness of
      ECMO in supporting this group of patients in the short-term. The self-limited
      natural history of many psychiatric episodes, poisonings and traumatic injuries
      makes the use of ECMO a potentially reasonable support strategy. However, careful
      consideration must be given to psychiatric history and follow-up given the
      substantial commitment of resources, potential for complications and for
      stranding patients on extracorporeal therapy without definitive destination
      therapy.

PMID- 29203212
TI  - Transcriptional basis of enhanced photoinduction of carotenoid biosynthesis at
      low temperature in the fungus Neurospora crassa.
AB  - Stimulation by light of carotenoid biosynthesis in the mycelia of the fungus
      Neurospora crassa starts with transient transcriptional induction of the
      structural genes of the pathway triggered by the White Collar photoreceptor
      complex. Most studies on this process were carried out under standard growth
      conditions, but photoinduced carotenoid accumulation is more efficient if the
      fungus is incubated at low temperatures, from 6 to 12  degrees C. We have
      investigated the transcriptional photoresponse at 8  degrees C of the genes for
      proteins that participate in the carotenoid pathway. Exposure to light pulses of
      different light intensities revealed higher sensitivity if the mycelia were
      subsequently incubated at 8  degrees C compared to 30  degrees C. Illumination of
      precooled mycelia resulted in delayed kinetics of mRNA accumulation for the
      structural genes, and high mRNA accumulation for a longer time. Additionally,
      after a light pulse, stronger reduction in mRNAs for carotenoid genes was
      observed at 30  degrees C compared to 8  degrees C. A similar pattern was found
      for mRNAs of the photoreceptor genes wc-1 and vvd, the latter involved in
      photoadaptation. These results suggest that the increased efficiency in
      carotenoid photoinduction at low temperature is due to the higher mRNA levels of
      the structural genes under these conditions.

PMID- 29203214
TI  - Unravelling the differences: comparative proteomic analysis of a clonal virulent
      and an attenuated Histomonas meleagridis strain.
AB  - The current study focused on Histomonas meleagridis, a unicellular protozoan,
      responsible for histomonosis in poultry. Recently, the occurrence of the disease
      increased due to the ban of effective chemotherapeutic drugs. Basic questions
      regarding the molecular biology, virulence mechanisms or even life cycle of the
      flagellate are still puzzling. In order to address some of these issues, we
      conducted a comparative proteomic analysis of a virulent and an attenuated H.
      meleagridis strain traced back to a single cell and propagated in vitro as
      monoxenic mono-eukaryotic cultures. Using two-dimensional electrophoresis (2-DE)
      for proteome visualization with computational 2-DE gel image and statistical
      analysis, upregulated proteins in either of the two H. meleagridis strains were
      detected. Statistical analysis fulfilling two criteria (>=threefold upregulation
      and P < 0.05) revealed 119 differentially expressed protein spots out of which 62
      spots were noticed in gels with proteins from the virulent and 57 spots in gels
      with proteins from the attenuated culture. Mass spectrometric analysis of 32
      protein spots upregulated in gels of the virulent strain identified 17 as H.
      meleagridis-specific. The identification revealed that these spots belonged to
      eight different proteins, with the majority related to cellular stress
      management. Two ubiquitous cellular proteins, actin and enolase, were upregulated
      in multiple gel positions in this strain, indicating either post-translational
      modification or truncation, or even both. Additionally, a known virulence factor
      named legumain cysteine peptidase was also detected. In contrast to this, mass
      spectrometric analysis of 49 protein spots, upregulated in gels of the attenuated
      strain, singled out 32 spots as specific for the flagellate. These spots were
      shown to correspond to 24 different proteins that reflect the increased
      metabolism, in vitro adaptation of the parasite, and amoeboid morphology. In
      addition to H. meleagridis proteins, the analysis identified differential
      expression of Escherichia coli DH5alpha proteins that could have been influenced
      by the co-cultivated H. meleagridis strain, indicating a reciprocal interaction
      of these two organisms during monoxenic cultivation.

PMID- 29203215
TI  - Transapical mitral replacement with anterior leaflet splitting: A novel technique
      to avoid left ventricular outflow tract obstruction.

PMID- 29203217
TI  - Facile conversion from biologic to mechanical prosthesis: A bailout for a hostile
      aortic root.

PMID- 29203216
TI  - The presence of multiple variants affects the clinical phenotype and prognosis in
      left ventricular noncompaction after surgery.

PMID- 29203218
TI  - The modern Hydra: Perioperative stroke and cardiac surgery.

PMID- 29203219
TI  - Through the looking glass: Avoiding a retrospective approach to new technology
      acquisition.

PMID- 29203220
TI  - Bilateral spontaneous anterior shoulder dislocation: A missed orthopedic injury
      mistaken as proximal neuropathy.
AB  - A number of orthopedic injuries can occur during epileptic seizures. Anterior
      shoulder dislocation is one such orthopedic injury that is quite rare. The
      shoulder dislocation may injure the brachial plexus. Besides seizures, the nerves
      can also be damaged by anticonvulsive therapy. Muscle wasting following a seizure
      can misguide a clinician to investigate only neural or muscular pathologies. We
      report here an individual with epilepsy who was referred to us for
      electrodiagnostic evaluation of proximal muscle wasting related to a suspected
      proximal neuropathy. He was found to have a normal electrodiagnostic evaluation
      and later on discovered to have had bilateral shoulder dislocation on X-rays.
      This report advocates a thorough clinical appraisal, radiographs, and
      electrodiagnostic evaluation in a case with muscle wasting following a seizure.

PMID- 29203221
TI  - Distal femoral physeal crush injury with metaphyseal comminution - A report of
      two cases and a new perspective to physeal injury.
AB  - The physis of a long bone may get 'sandwiched' and crushed between the metaphysis
      and the epiphysis if it is traumatically loaded along its long axis. Such a
      physeal injury may lead to complications like angular deformities and growth
      restrictions and hence, management of such injuries requires adequate planning
      and attentive execution. Two patients with distal femoral physeal crush injury
      were treated using a ring fixator such that one ring had the wires passing
      through the epiphysis and the other through the femoral shaft. On table image
      intensifier controlled distraction of the crushed physis was done to bring the
      height of the physis similar to that of the opposite limb. Patients were followed
      up for more than two years clinically and radiologically. There was no clinical
      or radiological angular deformity of the operated limbs. MRI scans showed intact
      physes with no physeal bar formation in either of the two patients. The
      distraction obtained by the ring fixator appears to have provided ample
      'breathing space' to the compressed physis and that the growth potential may have
      been re-gained by the procedure. However, two years is a relatively short
      duration of follow-up and further follow-up of longer duration and in greater
      number of patients is needed to gauge the actual effectiveness of the technique
      used by us.

PMID- 29203222
TI  - Methanol assimilation in Escherichia coli is improved by co-utilization of
      threonine and deletion of leucine-responsive regulatory protein.
AB  - Methane, the main component of natural gas, can be used to produce methanol which
      can be further converted to other valuable products. There is increasing interest
      in using biological systems for the production of fuels and chemicals from
      methanol, termed methylotrophy. In this work, we have examined methanol
      assimilation metabolism in a synthetic methylotrophic E. coli strain.
      Specifically, we applied 13C-tracers and evaluated 25 different co-substrates for
      methanol assimilation, including amino acids, sugars and organic acids. In
      particular, co-utilization of threonine significantly enhanced methylotrophy.
      Through our investigations, we proposed specific metabolic pathways that, when
      activated, correlated with increased methanol assimilation. These pathways are
      normally repressed by the leucine-responsive regulatory protein (lrp), a global
      regulator of metabolism associated with the feast-or-famine response in E. coli.
      By deleting lrp, we were able to further enhance the methylotrophic ability of
      our synthetic strain, as demonstrated through increased incorporation of 13C
      carbon from 13C-methanol into biomass.

PMID- 29203223
TI  - Expression of heterologous non-oxidative pentose phosphate pathway from Bacillus
      methanolicus and phosphoglucose isomerase deletion improves methanol assimilation
      and metabolite production by a synthetic Escherichia coli methylotroph.
AB  - Synthetic methylotrophy aims to develop non-native methylotrophic microorganisms
      to utilize methane or methanol to produce chemicals and biofuels. We report two
      complimentary strategies to further engineer a previously engineered
      methylotrophic E. coli strain for improved methanol utilization. First, we
      demonstrate improved methanol assimilation in the presence of small amounts of
      yeast extract by expressing the non-oxidative pentose phosphate pathway (PPP)
      from Bacillus methanolicus. Second, we demonstrate improved co-utilization of
      methanol and glucose by deleting the phosphoglucose isomerase gene (pgi), which
      rerouted glucose carbon flux through the oxidative PPP. Both strategies led to
      significant improvements in methanol assimilation as determined by 13C-labeling
      in intracellular metabolites. Introduction of an acetone-formation pathway in the
      pgi-deficient methylotrophic E. coli strain led to improved methanol utilization
      and acetone titers during glucose fed-batch fermentation.

PMID- 29203224
TI  - Mantle Cell Lymphoma Presenting as Lymphomatous Polyposis.

PMID- 29203225
TI  - Mucosal Healing and Long-term Outcomes of Patients With Inflammatory Bowel
      Diseases Receiving Clinic-Based vs Trough Concentration-Based Dosing of
      Infliximab.
AB  - BACKGROUND & AIMS: The Trough Concentration Adapted Infliximab Treatment (TAXIT)
      trial demonstrated that maintaining infliximab trough concentrations at 3 to 7
      MUg/mL is most effective at inducing remission in patients with inflammatory
      bowel diseases (IBDs), with fewer flares than clinic-based dosing. We performed a
      follow-up analysis of study participants to explore the correlation between
      trough dosing strategy and mucosal healing, continued infliximab use, and rates
      of hospitalization, surgery, and steroid use. METHODS: This was a retrospective
      single-center study of 226 patients with IBD who completed the maintenance phase
      of TAXIT, performed at the University Hospitals of Leuven in Belgium. Baseline
      patient characteristics, laboratory test results, and endoscopic data were
      obtained at the end of that study between June 2012 and December 2013 (n = 125).
      Long-term outcome data (IBD-related hospitalization, abdominal surgery, and
      systemic steroid use) were collected from the time of the last TAXIT study visit
      (August 2012-April 2013) until April 1, 2016. We also collected data on continued
      use of infliximab and trough concentrations. RESULTS: At baseline, 91% of
      patients in the clinic-based dosing group and 90% of patients in the trough
      concentration-based dosing group had mucosal healing. After a median follow-up
      time of 41 months (interquartile range, 39-42 mo), infliximab treatment was
      continued by 81 of 108 patients (75%) from the clinic-based dosing group and 86
      of 107 (80%) from the trough concentration-based dosing group. However, within 1
      year, infliximab was discontinued by 10 of 27 patients (37%) from the clinic
      based dosing group and 2 of 21 patients (10%) from the trough concentration-based
      dosing group (P = .04). The rates of hospitalization, surgery, and steroid use
      were below 15% in both groups. CONCLUSIONS: At the end of a trial of clinic-based
      dosing vs trough concentration-based dosing of infliximab in patients with IBD,
      most patients had mucosal healing. Most patients (>=75%) in both groups continued
      taking infliximab for more than 3 years after the trial, but a significantly
      higher proportion of patients in the clinic-based dosing group discontinued
      infliximab in the first year after the end of the trial. Both groups had low
      rates of hospitalization, surgery, and steroid use.

PMID- 29203226
TI  - Innately versatile: gammadelta17 T cells in inflammatory and autoimmune diseases.
AB  - IL-17-producing gammadelta (gammadelta17) T cells form a versatile subset of
      cells that respond rapidly to innate stimuli and support the pro-inflammatory
      functions of different myeloid and lymphoid lineages, being particularly critical
      in the early stages of inflammatory and autoimmune responses. In mice, under
      homeostatic conditions, these innate-like lymphocytes are pre-programmed in the
      fetal thymus, through an intricate process involving both T cell receptor
      dependent and -independent signals, which allows them to readily produce IL-17
      upon stimulation. However, given their transcriptional and epigenetic wiring,
      gammadelta17 T cells are permissive to different environmental instructions, and
      can readily acquire the ability to co-produce multiple cytokines, such as IFN
      gamma, IL-22 and GM-CSF, that further propagate inflammation. Moreover, strong IL
      23 signals, which are abundantly found in autoinflammatory conditions, are able
      to induce de novo differentiation of gammadelta17 T cells from uncommitted
      precursors, both in mice and humans. This notwithstanding, the exact mechanisms
      responsible for gammadelta17 T cell pathogenicity and multifunctionality are
      still poorly understood, especially in humans. The pathogenic roles attributed to
      gammadelta17 T cells in autoimmune diseases stem mainly from their ability to
      recruit different inflammatory myeloid populations to the target tissue, and to
      modulate alphabeta T cell function, either by enhancing inflammatory TH17
      responses, or by restraining regulatory Treg cell activity. Given their capacity
      to link key inflammatory axes of innate and adaptive immunity, a better
      understanding of the molecular basis underpinning gammadelta17 T cell plasticity,
      and how much this feature accounts for their pathophysiological roles, may be
      critical for developing novel therapeutic approaches. In this review, we discuss
      the importance of gammadelta17 T cells in breaking tolerance and enhancing
      inflammation in various autoimmune diseases, such as multiple sclerosis,
      psoriasis and rheumatoid arthritis under the light of their basic biological
      traits, e.g. development, activation, effector functions and plasticity.

PMID- 29203227
TI  - Behavior of Adult 5-HT1A Receptor Knockout Mice Exposed to Stress During Prenatal
      Development.
AB  - Chronic maternal stress during pregnancy can have long-term, detrimental
      consequences for the offspring. An understanding of the mechanisms responsible
      for mediating these effects is essential for devising therapeutic interventions.
      Here, we examined whether serotonin 1A receptor (5-HT1AR) mediates the effects of
      maternal stress on the behavioral outcomes of the offspring as adults.
      Heterozygous (HET) mouse dams were bred with HET males and were randomly assigned
      to stress or control groups. Pregnant dams in the stress group were exposed to a
      regime of chronic unpredictable stress from embryonic day 7 to 18. At two months
      of age, groups of male and female wildtype (WT), HET, and knockout (KO) offspring
      underwent a comprehensive behavioral test battery that included tests of social
      behavior, memory, aggression, anxiety, sensorimotor information processing, and
      exploratory and risk assessment behaviors. Independent of genotype, prenatal
      stress resulted in a change in locomotor activity and fear memory in male mice
      and a change in prepulse inhibition in female animals. 5-HT1AR KO affected
      anxiety in male mice, and fear memory and prepulse inhibition in female mice. 5
      HT1AR genotype moderated the effects of maternal prenatal stress exposure on
      social behavior of male offspring and on activity levels of female offspring. Our
      findings indicate that 5-HT1A receptor availability can affect outcomes of the
      offspring resulting from maternal prenatal stress exposure, and that these
      effects are sex-specific.

PMID- 29203229
TI  - Effects on Hedonic Feeding, Energy Expenditure and Balance of the Non-opioid
      Peptide DYN-A2-17.
AB  - The dynorphin (DYN) peptide family includes opioid and non-opioid peptides, yet
      the physiological role of the non-opioid DYN peptides remains poorly understood.
      Recent evidence shows that administering the non-opioid peptide DYN-A2-17 into
      the paraventricular hypothalamic nucleus (PVN) simultaneously increased short
      term intake of standard rodent chow and spontaneous physical activity (SPA). The
      present studies aimed to expand upon the mechanisms and role of DYN-A2-17 on food
      intake and energy expenditure. Injection of DYN-A2-17 in PVN increased SPA,
      energy expenditure and wheel running in the absence of food. Repeated DYN-A2-17
      injection in PVN increased short-term chow intake, but this effect habituated
      over time and failed to alter cumulative food intake, body weight or adiposity.
      Pre-treatment with a CRF receptor antagonist into PVN blocked the effects of DYN
      A2-17 on food intake while injection of DYN-A2-17 in PVN increased plasma ACTH.
      Finally, as DYN peptides are co-released with orexin peptides, we compared the
      effects of DYN-A2-17 to orexin-A and the opioid peptide DYN-A1-13 on food choice
      and intake in PVN when palatable snacks and chow were available. DYN-A1-13
      selectively increased intake of palatable snacks. DYN-A2-17 and orexin-A
      decreased palatable snack intake while orexin-A also increased chow intake. These
      findings demonstrate that the non-opioid peptide DYN-A2-17 acutely regulates
      physical activity, energy expenditure and food intake without long-term effects
      on energy balance. These data also propose different roles of opioid, non-opioid
      DYN and orexin peptides on food choice and intake when palatable and non
      palatable food options are available.

PMID- 29203228
TI  - Mild Fluid Percussion Injury Induces Diffuse Axonal Damage and Reactive Synaptic
      Plasticity in the Mouse Olfactory Bulb.
AB  - Despite the regenerative capacity of the olfactory bulb (OB), head trauma causes
      olfactory disturbances in up to 30% of patients. While models of olfactory nerve
      transection, olfactory receptor neuron (ORN) ablation, or direct OB impact have
      been used to examine OB recovery, these models are severe and not ideal for study
      of OB synaptic repair. We posited that a mild fluid percussion brain injury
      (mFPI), delivered over mid-dorsal cortex, would produce diffuse OB
      deafferentation without confounding pathology. Wild type FVB/NJ mice were
      subjected to mFPI and OB probed for ORN axon degeneration and onset of reactive
      synaptogenesis. OB extracts revealed 3 d postinjury elevation of calpain-cleaved
      150-kDa alphaII-spectrin, an indicator of axon damage, in tandem with reduced
      olfactory marker protein (OMP), a protein specific to intact ORN axons. Moreover,
      mFPI also produced a 3-d peak in GFAP+ astrocyte and IBA1+ microglial reactivity,
      consistent with postinjury inflammation. OB glomeruli showed disorganized ORN
      axons, presynaptic degeneration, and glial phagocytosis at 3 and 7 d postinjury,
      all indicative of deafferentation. At 21 d after mFPI, normal synaptic structure
      re-emerged along with OMP recovery, supporting ORN afferent reinnervation. Robust
      21 d postinjury upregulation of GAP-43 was consistent with the time course of ORN
      axon sprouting and synapse regeneration reported after more severe olfactory
      insult. Together, these findings define a cycle of synaptic degeneration and
      recovery at a site remote to non-contusive brain injury. We show that mFPI models
      diffuse ORN axon damage, useful for the study of time-dependent reactive
      synaptogenesis in the deafferented OB.

PMID- 29203230
TI  - Maternal Consumption of High-fat Diet in Mice Alters Hypothalamic Notch Pathway,
      NPY Cell Population and Food Intake in Offspring.
AB  - Studies show that maternal consumption of a high-fat diet (HFD) can impair the
      formation of hypothalamic neuronal circuits in mouse offspring. This damage can
      be mediated by Notch1/Hes5 signaling activation, leading to repression of
      proneural factors such as Mash1 and Ngn2/3, which are essential for neuronal
      differentiation and neurogenesis. Thus, we aimed to investigate the effects of
      maternal HFD consumption during gestation and lactation on the Notch1/Mash1
      pathway in the hypothalamus and arcuate nucleus (ARC) of mouse offspring
      (neonates and 28 days old). Our results showed that maternal HFD consumption
      increases body weight and adiposity of mouse offspring, accompanied by increased
      levels of Il-1beta mRNA compared to those in control offspring. We noticed high
      mRNA levels of Hes5 accompanied by diminished mRNA levels of Ascl1 (Mash1). The
      number of Mash1-labeled cells in the ARC was diminished in HFD-O. Additionally,
      the population of NPY neurons was increased in these animals. Mash1 is important
      for the development of POMC and NPY neurons in the ARC. Therefore, the reduction
      in Mash1-labeled cells could be related to modification of the NPY neuron
      population in the ARC. This scenario favors hyperphagia and weight gain, and
      could be responsible for the development of obesity in adulthood.

PMID- 29203231
TI  - A test of four innominate bone age assessment methods in a modern skeletal
      collection from Medellin, Colombia.
AB  - Studying bone collections with known data has proven to be useful in assessing
      reliability and accuracy of biological profile reconstruction methods used in
      Forensic Anthropology. Thus, it is necessary to calibrate these methods to
      clarify issues such as population variability and accuracy of estimations for the
      elderly. This work considers observations of morphological features examined by
      four innominate bone age assessment methods: (1) Suchey-Brooks Pubic Symphysis,
      (2) Lovejoy Iliac Auricular Surface, (3) Buckberry and Chamberlain Iliac
      Auricular Surface, and (4) Rouge-Maillart Iliac Auricular Surface and Acetabulum.
      This study conducted a blind test of a sample of 277 individuals from two
      contemporary skeletal collections from Universal and San Pedro cemeteries in
      Medellin, for which known pre-mortem data support the statistical analysis of
      results obtained using the four age assessment methods. Results from every method
      show tendency to increase bias and inaccuracy in relation to age, but Buckberry
      Chamberlain and Rouge-Maillart's methods are the most precise for this particular
      Colombian population, where Buckberry-Chamberlain's is the best for analysis of
      older individuals.

PMID- 29203232
TI  - Thioredoxin-interacting protein deficiency ameliorates diabetic retinal
      angiogenesis.
AB  - Diabetic retinopathy is the leading cause of blindness among working-aged adults
      around the world. Hyperglycemia and intraocular vascular endothelial growth
      factor (VEGF) over-accumulation are essential for the progression of diabetic
      retinopathy, which eventually results in proliferative diabetic retinopathy,
      characterized by pathologic angiogenesis and impaired vision. Thioredoxin
      interacting protein (TXNIP) was highly induced in retinal endothelial cells under
      diabetic conditions. However, the role of TXNIP in diabetes-associated retinal
      angiogenesis remains elusive. Here, we investigated whether the absence of TXNIP
      alters diabetes-associated retinal angiogenesis. Exposure of human retinal
      microvascular endothelial cells (HRMECs) to moderately high glucose (MHG)
      promoted cell migration and tube formation, but not proliferation. Knockdown of
      TXNIP suppressed moderately high glucose (MHG)-induced reactive oxygen species
      (ROS) generation, migration, tube formation and activation of Akt/mTOR pathway in
      HRMECs. Moreover, gene silencing of TXNIP inhibited VEGF-induced angiogenic
      response by blocking VEGFR2 and downstream signal pathway Akt/mTOR activation in
      HRMECs. Furthermore, TXNIP knockout inhibited VEGF or VEGF and MHG-induced
      retinal angiogenesis ex vivo compared with wild-type mice. In conclusion, our
      study demonstrated that TXNIP deficiency inhibited VEGF or/and MHG-induced
      angiogenic response in HRMECs and mice retinas and suggested TXNIP may be a
      potential therapy target for treating proliferative diabetic retinopathy.

PMID- 29203234
TI  - Development of a brief assessment of activity limitations in children with food
      allergy.

PMID- 29203233
TI  - Glycerophosphodiesterase GDE2/GDPD5 affects pancreas differentiation in
      zebrafish.
AB  - Notch signaling plays an essential role in the proliferation, differentiation and
      cell fate determination of various tissues, including the developing pancreas.
      One regulator of the Notch pathway is GDE2 (or GDPD5), a transmembrane ecto
      phosphodiesterase that cleaves GPI-anchored proteins at the plasma membrane,
      including a Notch ligand regulator. Here we report that Gdpd5-knockdown in
      zebrafish embryos leads to developmental defects, particularly, impaired motility
      and reduced pancreas differentiation, as shown by decreased expression of insulin
      and other pancreatic markers. Exogenous expression of human GDE2, but not
      catalytically dead GDE2, similarly leads to developmental defects. Human GDE2
      restores insulin expression in Gdpd5a-depleted zebrafish embryos. Importantly,
      zebrafish Gdpd5 orthologues localize to the plasma membrane where they show
      catalytic activity against GPI-anchored GPC6. Thus, our data reveal functional
      conservation between zebrafish Gdpd5 and human GDE2, and suggest that strict
      regulation of GDE2 expression and catalytic activity is critical for correct
      embryonic patterning. In particular, our data uncover a role for GDE2 in
      regulating pancreas differentiation.

PMID- 29203235
TI  - Sensibility and specificity of laser speckle contrast imaging according to Endo
      PAT index in type 1 diabetes.
AB  - OBJECTIVES: To find out an normality value for microvascular response
      (physiological and pharmacological) assessed through laser speckle contrast
      imaging (LSCI) based on Endo-PAT, which identifies the ones with Endothelial
      Dysfunction (ED) in patients with Type 1 Diabetes (T1D). METHODS: Patients with
      T1D, aged >=12years underwent a clinical-epidemiological questionnaire. Fasting
      blood samples were obtained (lipid profile, glycemic control and levels of C
      reactive protein). Vascular reactivity was assessed in the forearm through the
      technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH)
      and during iontophoresis of acetylcholine (ACh) and peripheral arterial tonometry
      was performed by supplying the RHI through Endo-PAT device. RESULTS: 189 patients
      were evaluated, 97 women (51.3%) with T1D, aged 32+/-13years and with a disease
      duration of 16 (6-21) years and mean A1c of 9.2% (+/-2.2). Receiver Operating
      Characteristics curve (ROC) analysis according to RHI showed that the Area under
      curve (AUC) of ACh of 10,369 Laser Speckle Perfusion Unit (LSPU) presented
      sensitivity and specificity of 65% and 87,5%, respectively, (p=0.002) in those
      patients with T1D's duration <5years. Overall, no test of vascular reactivity was
      able to distinguish the ideal cuttoff based on RHI. CONCLUSION: In the present
      study, we could find an ideal cut off value of microcirculation assessment
      through endothelium-dependent vasodilation to ACh using LSCI according to Endo
      PAT's score, only in those under 5years of disease duration. Further prospective
      studies shall be conducted to evaluate its predictive cardiovascular value.

PMID- 29203236
TI  - Amylin - Its role in the homeostatic and hedonic control of eating and recent
      developments of amylin analogs to treat obesity.
AB  - BACKGROUND: Amylin is a pancreatic beta-cell hormone that produces effects in
      several different organ systems. One of its best-characterized effects is the
      reduction in eating and body weight seen in preclinical and clinical studies.
      Amylin activates specific receptors, a portion of which it shares with calcitonin
      gene-related peptide (CGRP). Amylin's role in the control of energy metabolism
      relates to its satiating effect, but recent data indicate that amylin may also
      affect hedonic aspects in the control of eating, including a reduction of the
      rewarding value of food. Recently, several amylin-based peptides have been
      characterized. Pramlintide (Symlin(r)) is currently the only one being used
      clinically to treat type 1 and type 2 diabetes. However other amylin analogs with
      improved pharmacokinetic properties are being considered as anti-obesity
      treatment strategies. Several other studies in obesity have shown that amylin
      agonists could also be useful for weight loss, especially in combination with
      other agents. SCOPE OF REVIEW: This review will briefly summarize amylin
      physiology and pharmacology and then focus on amylin's role in food reward and
      the effects of amylin analogs in pre-clinical testing for anti-obesity drugs.
      CONCLUSION: We propose here that the effects of amylin may be homeostatic and
      hedonic in nature.

PMID- 29203237
TI  - Adiponectin release and insulin receptor targeting share trans-Golgi-dependent
      endosomal trafficking routes.
AB  - OBJECTIVE: Intracellular vesicle trafficking maintains cellular structures and
      functions. The assembly of cargo-laden vesicles at the trans-Golgi network is
      initiated by the ARF family of small GTPases. Here, we demonstrate the role of
      the trans-Golgi localized monomeric GTPase ARFRP1 in endosomal-mediated vesicle
      trafficking of mature adipocytes. METHODS: Control (Arfrp1flox/flox) and
      inducible fat-specific Arfrp1 knockout (Arfrp1iAT-/-) mice were metabolically
      characterized. In vitro experiments on mature 3T3-L1 cells and primary mouse
      adipocytes were conducted to validate the impact of ARFRP1 on localization of
      adiponectin and the insulin receptor. Finally, secretion and transferrin-based
      uptake and recycling assays were performed with HeLa and HeLa M-C1 cells.
      RESULTS: We identified the ARFRP1-based sorting machinery to be involved in
      vesicle trafficking relying on the endosomal compartment for cell surface
      delivery. Secretion of adiponectin from fat depots was selectively reduced in
      Arfrp1iAT-/- mice, and Arfrp1-depleted 3T3-L1 adipocytes revealed an accumulation
      of adiponectin in Rab11-positive endosomes. Plasma adiponectin deficiency of
      Arfrp1iAT-/- mice resulted in deteriorated hepatic insulin sensitivity, increased
      gluconeogenesis and elevated fasting blood glucose levels. Additionally, the
      insulin receptor, undergoing endocytic recycling after ligand binding, was less
      abundant at the plasma membrane of adipocytes lacking Arfrp1. This had
      detrimental effects on adipose insulin signaling, followed by insufficient
      suppression of basal lipolytic activity and impaired adipose tissue expansion.
      CONCLUSIONS: Our findings suggest that adiponectin secretion and insulin receptor
      surface targeting utilize the same post-Golgi trafficking pathways that are
      essential for an appropriate systemic insulin sensitivity and glucose
      homeostasis.

PMID- 29203238
TI  - Targeting erythropoietin protects against proteinuria in type 2 diabetic patients
      and in zebrafish.
AB  - OBJECTIVE: Adult human kidneys produce erythropoietin (EPO), which regulates red
      blood cell formation; however, whether EPO also functions directly on kidney
      development and controls diabetic kidney disease remains unknown. Here we
      analyzed the role of EPO in kidney development and under hyperglycemic conditions
      in zebrafish and in humans. METHODS: Diabetic patients and respective controls
      were enrolled in two cohorts. Serum EPO level and urine protein change upon human
      EPO administration were then analyzed. Transient knockdown and permanent knockout
      of EPO and EPOR in renal TG(WT1B:EGFP) zebrafish were established using the
      morpholino technology and CRISPR/Cas9 technology. Zebrafish embryos were
      phenotypically analyzed using fluorescence microscopy, and functional assays were
      carried out with the help of TexasRed labeled 70 kDa Dextran. Apoptosis was
      determined using the TUNEL assay and Annexin V staining, and caspase inhibitor
      zVADfmk was used for rescue experiments. RESULTS: In type 2 diabetic patients,
      serum EPO level decreased with the duration of diabetes, which was linked to
      reduced kidney function. Human recombinant EPO supplementation ameliorated
      proteinuria in diabetic nephropathy patients. In zebrafish, loss-of-function
      studies for EPO and EPOR, showed morphological and functional alterations within
      the pronephros, adversely affecting pronephric structure, leading to slit
      diaphragm dysfunction by increasing apoptosis within the pronephros. Induction of
      hyperglycemia in zebrafish embryos induced pronephros alterations which were
      further worsened upon silencing of EPO expression. CONCLUSIONS: EPO was
      identified as a direct renal protective factor, promoting renal embryonic
      development and protecting kidneys from hyperglycemia induced nephropathy.

PMID- 29203239
TI  - Piperine induces osteoblast differentiation through AMPK-dependent Runx2
      expression.
AB  - Piperine is an alkaloid responsible for the pungency of black pepper and long
      pepper. It is reported to have various biological actions such as anti-oxidative
      and anti-inflammatory, and aids cancer prevention. Antioxidants have been shown
      to promote osteoblast differentiation. However, osteoblast differentiation by
      piperine has not yet been elucidated. Piperine-induced expression of the
      osteogenic genes such as distal-less homeobox 5 (Dlx5), inhibitor of DNA binding
      1 (Id1), and runt-related transcription factor 2 (Runx2) was investigated using
      RT-PCR. In addition, alkaline phosphatase (ALP) activity and mineralization was
      found to be increased by piperine treatment. Finally, we confirmed that piperine
      induced phosphorylation of AMPK in MC3T3-E1 cells. Taken together, these results
      demonstrate that piperine enhance osteoblast differentiation through AMPK
      phosphorylation in MC3T3-E1 cells.

PMID- 29203240
TI  - IL-13 regulates IL-17C expression by suppressing NF-kappaB-mediated
      transcriptional activation in airway epithelial cells.
AB  - The cytokine interleukin (IL)-17C is highly expressed in epithelial tissues and
      involved in innate immune responses; however, the regulation of IL-17C expression
      in the airways remains poorly understood. Here, we show that IL-1beta strongly
      induces both IL-17C mRNA and protein expression in primary normal human bronchial
      epithelial cells. Conversely, IL-13 significantly reduced the IL-1beta-induced IL
      17C expression. Attenuation of the nuclear factor (NF)-kappaB-signaling pathway
      using an NF-kappaB-subunit p65-specific small-interfering RNA (siRNA), reduced IL
      1beta-induced IL-17C expression, demonstrating the importance of NF-kappaB
      signaling in IL-17C regulation. The inhibitory effects of IL-13 on IL-17C
      expression were abolished when the Janus kinase (JAK)/signal transducer and
      activator of transcription 6 (STAT6)-signaling pathway was impaired, using either
      the JAK inhibitor ruxolitinib or a STAT6-specific siRNA. Western blot analysis
      demonstrated that IL-1beta promoted both IkappaB-alpha phosphorylation and
      degradation, and p65 nuclear translocation. Although IL-13 induced STAT6
      phosphorylation and nuclear translocation, it did not affect the activation of
      the IL-1beta-mediated NF-kappaB-pathway. Using chromatin immunoprecipitation, we
      confirmed that IL-1beta enhanced p65 binding to regions within the IL-17C
      promoter that flank putative NF-kappaB-binding sites (-130/-120 and -157/-147).
      Interestingly, IL-13 treatment reduced the IL-1beta-mediated p65 binding to these
      regions. These findings demonstrate that NF-kappaB-mediated transcriptional
      mechanisms are critically involved in the IL-1beta-mediated IL-17C induction, and
      that IL-13 negatively regulates this induction by suppressing NF-kappaB-based
      transcriptional activation.

PMID- 29203242
TI  - An actin-based nucleoskeleton involved in gene regulation and genome
      organization.
AB  - In eukaryotic cells gene regulation is dependent on global genome organization.
      This is achieved, in response to favorable environmental conditions, through
      spatial redistribution of chromatin and changes in global epigenetic levels. This
      eventually drives movement of gene-rich chromatin loops and formation of DNA
      loops, consolidating neighborhoods of gene expression and silencing. One of the
      challenges for future work is to examine how these neighborhoods are formed and
      whether they host genes involved in the same cellular functions for sustained
      expression or silencing over time. In the present review, we summarize evidence
      that actin and actin-associated proteins regulate gene activity. Furthermore we
      discuss how these specific nuclear tasks in which actin is engaged are important
      to organize and consolidate the mammalian genome, ensuring gene activation and
      repression of gene programs important to establish cellular identity. We propose
      that these mechanisms are essential to control cellular development and
      differentiation.

PMID- 29203241
TI  - The splicing factor transformer2 (tra2) functions in the Drosophila fat body to
      regulate lipid storage.
AB  - Excess nutrients are stored as triglycerides mainly in the adipose tissue of an
      animal and these triglycerides are located in structures called lipid droplets.
      Previous genome-wide RNAi screens in Drosophila cells identified splicing factors
      as playing a role in lipid droplet formation. Our lab has recently identified the
      SR protein, 9G8, as an important factor in fat storage as decreasing its levels
      results in augmented triglyceride storage in the fat body. Previous in vitro
      studies have implicated 9G8 in the regulation of splicing of the sex
      determination gene doublesex (dsx) by binding to transformer (tra) and
      transformer2 (tra2); however, any function of these sex determination proteins in
      regulating metabolism is unknown. In this study, we have uncovered a role of tra2
      to regulate fat storage in vivo. Inducing tra2dsRNA in the adult fat body
      resulted in an increase in triglyceride levels but had no effect on glycogen
      storage. Consistent with the triglyceride phenotype, tra2 knockdown flies lived
      longer under starvation conditions. In addition, this increase in triglycerides
      is due to more fat storage per cell and not an increase in the number of fat
      cells. Interestingly, the splicing of CPT1, an enzyme involved in the breakdown
      of lipids, was altered in flies with decreased tra2. The less-catalytically
      active isoform of CPT1 accumulated in tra2dsRNA flies suggesting a decrease in
      lipid breakdown, which is consistent with the increased triglyceride levels
      observed in these flies. Together, these results suggest a link between mRNA
      splicing, sex determination and lipid metabolism and may provide insight into the
      mechanisms underlying tissue-specific splicing and nutrient storage.

PMID- 29203243
TI  - Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.
AB  - Rottlerin has been reported to exert its anti-tumor activity in various types of
      human cancers. However, the underlying molecular mechanism has not been fully
      elucidated. In the current study, we explored whether rottlerin exhibits its
      tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay
      results showed that rottlerin inhibited cell growth in hepatocellular carcinoma
      cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell
      cycle arrest at G1 phase. Furthermore, our wound healing assay result
      demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma
      cells. Additionally, rottlerin suppressed cell migration and invasion. Notably,
      we found that rottlerin upregulated DDX3 expression and subsequently
      downregulated Cyclin D1 expression and increased p21 level. Importantly, down
      regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function,
      whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our
      study suggests that rottlerin exhibits its anti-cancer activity partly due to
      upregulation of DDX3 in hepatocellular carcinoma cells.

PMID- 29203244
TI  - MicroRNA-126 alleviates endothelial cells injury in atherosclerosis by restoring
      autophagic flux via inhibiting of PI3K/Akt/mTOR pathway.
AB  - MicroRNAs (miRNAs) have emerged as critical modulators of ECs function and play a
      vital role in the development of cardiovascular disease. Among them, miR-126 is a
      crucial regulator of atherosclerosis. Endothelial cells (ECs) death and autophagy
      have been described in cells to cope with the progression of atherosclerosis.
      Hence, the aim of this study is to investigate the effects of miR-126 on
      atherosclerosis in oxidized low-density lipoprotein (ox-LDL)-stimulated human
      umbilical vein endothelial cells (HUVECs) and the potential roles of autophagy
      flux in these processes. Our results showed that miR-126 level was significantly
      reduced in ox-LDL-treated HUVECs and miR-126 overexpression induced by miR-126
      mimics remarkably blocked ox-LDL-induced HUVECs injury as evidenced by the
      reduced cell viability, and the increased LDH release, caspase-3 activity and
      apoptosis ratio. In addition, ox-LDL increased LC3-II, Beclin 1, and p62
      expressions in HUVECs, while these changes were nullified in the presence of
      treatment with bafilomycin A1 (BafA1, an inhibit autophagic flux inhibitor).
      However, we found that ox-LDL-induced impaired autophagy flux was recused by miR
      126 mimics. Subsequently, we found that Bafi A1 pretreatment reversed the
      protection of miR-126 mimics against ox-LDL-induced HUVECs injury. Finally, our
      results showed that miR-126 mimics rescued ox-LDL-induced impaired autophagy flux
      through inhibiting PI3K/Akt/mTOR signaling. Taken together, our findings
      suggested that miR-126 alleviates ox-LDL-induced HUVECs injury through restoring
      autophagy flux via repressing PI3K/Akt/mTOR pathway, and further implicate the
      potential therapeutic targets to reverse atherosclerosis.

PMID- 29203245
TI  - KLF4 protects brain microvascular endothelial cells from ischemic stroke induced
      apoptosis by transcriptionally activating MALAT1.
AB  - In this study, we investigated the expression profile and functional role of
      Kruppel-like family of transcription factor 4 (KLF4) in mouse cerebral
      microvascular endothelial cells (MECs) after focal cerebral ischemia and in
      cultured b.End3 cells after oxygen-glucose deprivation (OGD). Its downstream
      regulation was also studied. Our data showed that KLF4 was significantly
      upregulated in the cerebral MECs after transient ischemic insult and in cultured
      b.End3 cells after 24 h OGD exposure. In in vitro b.End3 cell model, KLF4 shRNA
      significantly increased OGD-induced activation of caspase-3 and also increased
      OGD-induced b.End3 cell death. KLF4 shRNA substantially enhanced OGD induced Bim
      and Bax expression at mRNA and protein levels and also aggravated OGD induced
      upregulation of E-selectin, MCP-1 and IL-6. Bioinformatic analysis suggested that
      MALAT1 promoter has a possible KLF4 binding site. In this study, we validated
      this possible binding site and also demonstrated that enforced KLF4 expression
      increased MALAT1 transcription. Functionally, knockdown of MALAT1 phenocopied the
      effect of KLF4 shRNA on enhancing OGD induced cell apoptosis and OGD induced
      upregulation of pro-apoptotic factors and pro-inflammatory cytokines. Based on
      these findings, we infer that MALAT1 is a transcriptional target of KLF4 in its
      protective role in cerebral MECs after ischemic insult.

PMID- 29203246
TI  - The role of Protein Disulfide Isomerase and thiol bonds modifications in
      activation of integrin subunit alpha11.
AB  - Integrins belong to a family of transmembrane receptors that mediate cell
      migration and adhesion to ECM. Extracellular domains of integrin heterodimers
      contain cysteine-rich regions, which are potential sites of thiol-disulfide
      exchanges. Rearrangements of extracellular disulfide bonds regulate activation of
      integrin receptors by promoting transition from an inactive state into a ligand
      binding competent state. Modifications of integrin disulfide bonds dependent on
      oxidation-reduction can be mediated by Protein Disulfide Isomerse (PDI). This
      paper provides evidences that binding to integrin ligands initiate changes in
      free thiol pattern on cell surface and that thiol-disulfide exchange mediated by
      PDI leads to activation of integrin subunit alpha11. By employing co
      immunoprecipitation and confocal microscopy analysis we showed that alpha11beta1
      and PDI create complexes bounded by disulfide bonds. Using surface plasmon
      resonance we provide biochemical evidence that PDI can interact directly with
      integrin subunit alpha11.

PMID- 29203247
TI  - Co-administration of APD668, a G protein-coupled receptor 119 agonist and
      linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in mice
      fed on a high trans-fat diet.
AB  - Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic
      Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic
      steatosis, oxidative stress, inflammation, hepatocyte injury with or without
      fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for
      the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present
      study, we investigated the effect of APD668, a GPR119 agonist alone or in
      combination with linagliptin, a DPPIV inhibitor on the progression of
      steatohepatitis in mice fed on a high trans-fat diet. In this study, monotherapy
      with either APD668 or linagliptin caused a reduction in the levels of ALT, AST,
      glucose, cholesterol and epididymal fat mass but the effect was more pronounced
      upon treatment with combination of both drugs. On the other hand, combined
      treatment of APD668 with linagliptin demonstrated a non-significant additive
      effect in reduction of hepatic triglyceride (-78%) and cholesterol (-56%)
      compared to monotherapy groups. Moreover, co-administration of APD668 and
      linagliptin resulted in enhanced levels of active GLP-1 with additional benefit
      of significant synergistic decrease in body weight gain (-19%) in mice. We
      speculated that the enhanced effect observed with the combination treatment could
      be due to either 1) direct activation of GPR119 receptors present in liver and
      intestine or 2) enhanced active GLP-1 levels or 3) decreased degradation of GLP-1
      in-vivo through DPPIV inhibition. Therefore, these findings clearly suggest that
      GPR119 receptor agonists in combination with DPPIV inhibitors may represent a
      promising therapeutic strategy for the treatment of non-alcoholic
      steatohepatitis.

PMID- 29203248
TI  - Vms1: A Cytosolic CAT-Tailing Antagonist to Protect Mitochondria.
AB  - In eukaryotes, a cytosolic ribosome quality control complex recycles erroneously
      stalled ribosomes and modifies faulty nascent chains by ubiquitination and by C
      terminal Ala- and Thr-extension (CAT-tailing). Reported recently in Cell, Izawa
      et al. identify cytosolic Vms1 (VCP/Cdc48-associated mitochondrial stress
      responsive 1) as an inhibitor of CAT-tailing, which prevents mitochondrial
      dysfunction caused by imported CAT-tailed polypeptides.

PMID- 29203249
TI  - Silent Acute Interstitial Nephritis: Suspicion Is the Key to Diagnosis.

PMID- 29203250
TI  - NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in
      colorectal cancer via the enhancement of CHK1 signaling.
AB  - As a third-generation platinum drug, oxaliplatin has been widely applied in
      colorectal cancer (CRC); however, acquired resistance to oxaliplatin has become a
      major obstacle. In the present study, we found that the nuclear transcription
      factor Y subunit beta (NFYB) and E2F transcription factor 1 (E2F1) expression
      levels were significantly higher in oxaliplatin-resistant DLD1 and RKO CRC (OR
      CRC) cells than in non-resistant cells. Additionally, highly expressed NFYB
      transactivated the E2F1 gene, which is important to maintain oxaliplatin
      resistance in OR-CRC cells. And Sirt1-dependent deacetylation suppresses the
      proapoptotic activity of E2F1 in OR-CRC cells. Through profiling the
      transcriptome of OR-CRC cells following E2F1 knockdown, CHK1 was identified as a
      target of E2F1. Deprivation of CHK1 sensitized OR-CRC cells to oxaliplatin. In
      vitro and in vivo phenotype experiments confirmed that an intact NFYB-E2F1-CHK1
      axis was required to suppress oxaliplatin-induced apoptosis and maintain the
      tumorigenicity in OR-CRC cells. Knockdown of E2F1 in OR-CRC cells also decreased
      the expression of Pol kappa, which was essential for CHK1 activation.
      Consistently, a high level of NFYB, E2F1, or CHK1 predicted poor survival in CRC
      patients, especially with oxaliplatin treatment. Collectively, the NFYB-E2F1
      pathway displays a crucial role in the chemoresistance of OR-CRC by inducing the
      expression and activation of CHK1, providing a possible therapeutic target for
      oxaliplatin resistance in CRC.

PMID- 29203251
TI  - Androgen receptor (AR) degradation enhancer ASC-J9(r) in an FDA-approved
      formulated solution suppresses castration resistant prostate cancer cell growth.
AB  - ASC-J9(r) is a recently-developed androgen receptor (AR)-degradation enhancer
      that effectively suppresses castration resistant prostate cancer (PCa) cell
      proliferation and invasion. The optimal half maximum inhibitory concentrations
      (IC50) of ASC-J9(r) at various PCa cell confluences (20%, 50%, and 100%) were
      assessed via both short-term MTT growth assays and long-term clonogenic
      proliferation assays. Our results indicate that the IC50 values for ASC-J9(r)
      increased with increasing cell confluency. The IC50 values were significantly
      decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal
      prostate cells. This suggests that ASC-J9(r) may function mainly via targeting
      the AR-positive PCa cells with limited unwanted side-effects to suppress the
      surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9(r)
      might function via altering the apoptosis signals to suppress the PCa AR-negative
      PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in
      vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells
      demonstrated that ASC-J9(r) has similar AR degradation effects when dissolved in
      FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5),
      DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together,
      results from preclinical studies suggest a potential new therapy with AR
      degradation enhancer ASC-J9(r) may potentially be ready to be used in human
      clinical trials in order to better suppress PCa at later castration resistant
      stages.

PMID- 29203252
TI  - Occurrence and improvement of renal dysfunction and serum potassium abnormality
      during administration of liposomal amphotericin B in patients with hematological
      disorders: A retrospective analysis.
AB  - Liposomal amphotericin B (L-AMB) has the potential to cause two major adverse
      events, renal dysfunction and serum potassium abnormality; however, appropriate
      clinical management of these events remains unclear. We retrospectively analyzed
      data regarding 128 hematology patients who received L-AMB in our institute and
      examined the association between clinical characteristics and renal dysfunction
      or serum potassium abnormality. We found that the median weight-normalized dose
      of L-AMB was 2.69mg/kg and the median administration period was 16days. The
      overall occurrence rates of renal dysfunction and hypokalemia were 55.7% and
      76.6%, respectively. Multivariate analysis revealed that pre-existing renal
      dysfunction (P=0.017) and concomitant use of nephrotoxic (P<0.0001) or antifungal
      drugs (P=0.012) were independent risk factors for renal dysfunction. A higher
      infusion volume did not mitigate the risk of renal dysfunction. Hypokalemia
      occurred significantly less often in men (P=0.028) and in patients who
      concomitantly used nephrotoxic drugs (P=0.013). Approximately 40% of the adverse
      events were improved at 30days after L-AMB termination and there was no
      significant association between these adverse events improvement and L-AMB dosage
      or infusion volume. Of note, hyperkalemia was observed in more patients who
      received allogeneic hematopoietic stem cell transplantation (P=0.0303) and
      concomitant treatment with nephrotoxic drugs (P=0.0281). These results suggest
      that imprudent reduction of L-AMB dose or redundant intravenous infusion may have
      minimal benefit for critical patients with suspected invasive fungal infection.

PMID- 29203253
TI  - Type 2 diabetes mellitus management among Ghanaian migrants resident in three
      European countries and their compatriots in rural and urban Ghana - The RODAM
      study.
AB  - AIMS: To compare Type 2 Diabetes Mellitus (T2DM) awareness, treatment and control
      between Ghanaians resident in Ghana and Europe. METHODS: Comparisons were made
      for the 530 participants of the Research on Obesity and Diabetes among African
      Migrants (RODAM) study with T2DM (25-70 years) living in Amsterdam, Berlin,
      London, urban Ghana and rural Ghana. We used logistic regression to assess
      disparities with adjustment for age, sex and education. RESULTS: T2DM awareness
      was 51% in rural Ghana. This was lower than levels in Europe ranging from 73% in
      London (age-sex adjusted odds ratio (OR) = 2.7; 95%CI = 1.2-6.0) to 79% in
      Amsterdam (OR = 4.7; 95%CI = 2.3-9.6). T2DM treatment was also lower in rural
      Ghana (37%) than in urban Ghana (56%; OR = 2.6; 95%CI = 1.3-5.3) and European
      sites ranging from 67% in London (OR = 3.4; 95%CI = 1.5-7.5) to 73% in Berlin (OR
      = 6.9; 95%CI = 2.9-16.4). In contrast, T2DM control in rural Ghana (63%) was
      comparable to Amsterdam and Berlin, but higher than in London (40%; OR = 0.4;
      95%CI = 0.2-0.9) and urban Ghana (28%; OR = 0.3; 95%CI = 0.1-0.6). CONCLUSIONS:
      Our findings suggest that improved detection and treatment of T2DM in rural
      Ghana, and improved control for people with diagnosed T2DM in London and urban
      Ghana warrant prioritization. Further work is needed to understand the factors
      driving the differences.

PMID- 29203254
TI  - Ethnic dependent differences in diagnostic accuracy of glycated hemoglobin
      (HbA1c) in Canadian adults.
AB  - AIM: Previous studies have shown varying sensitivity and specificity of
      hemoglobin A1c (HbA1c) to identify diabetes and prediabetes, compared to 2-h oral
      glucose tolerance testing (OGTT) and fasting plasma glucose (FPG), in different
      ethnic groups. Within the Canadian population, the ability of HbA1c to identify
      prediabetes and diabetes in First Nations, Metis and Inuit, East and South Asian
      ethnic groups has yet to be determined. METHODS: We collected demographic,
      lifestyle information, biochemical results of glycemic status (FPG, OGTT, and
      HbA1c) from an ethnically diverse Canadian population sample, which included a
      purposeful sampling of First Nations, Metis, Inuit, South Asian and East Asian
      participants. RESULTS: Sensitivity and specificity using Canadian Diabetes
      Association (CDA) recommended cut-points varied between ethnic groups, with
      greater variability for identification of prediabetes than diabetes. Dysglycemia
      (prediabetes and diabetes) was identified with a sensitivity and specificity
      ranging from 47.1% to 87.5%, respectively in Caucasians to 24.1% and 88.8% in
      Inuit. Optimal HbA1c ethnic-specific cut-points for dysglycemia and diabetes were
      determined by receiver operating characteristic (ROC) curve analysis.
      CONCLUSIONS: Our sample showed broad differences in the ability of HbA1c to
      identify dysglycemia or diabetes in different ethnic groups. Optimal cut-points
      for dysglycemia or diabetes in all ethnic groups were substantially lower than
      CDA recommendations. Utilization of HbA1c as the sole biochemical diagnostic
      marker may produce varying degrees of false negative results depending on the
      ethnicity of screened individuals. Further research is necessary to identify and
      validate optimal ethnic specific cut-points used for diabetic screening in the
      Canadian population.

PMID- 29203255
TI  - Increasing prevalence of type 2 diabetes mellitus and impact of ethnicity in
      north Sudan.
AB  - BACKGROUND: Diabetes mellitus constitutes a global health threat, with increasing
      burden of disease in low and middle-income countries witnessing ongoing
      epidemiological transition including Sudan. AIMS: To study the prevalence of type
      2 diabetes mellitus (T2DM) and prediabetes and determine the relationship to
      gender, age, waist circumference, body mass index, residence and ethnicity among
      the adult population in north Sudan. METHODS: A cross-sectional, population-based
      study in Northern State and River Nile State using random multi-stage cluster
      sampling targeting 5376 participants from 14 localities divided into 60 urban and
      40 rural clusters. In each cluster, 60 households were studied. Blood glucose
      level and anthropometric measurements were recorded and a questionnaire
      containing demographic data was obtained from each participant. RESULTS: The
      prevalence of T2DM among participants was 18.7% and prediabetes was 12.9%. Among
      people living with T2DM, 694(71.0%) were known cases of T2DM, whereas 284(29.0%)
      were newly diagnosed cases. The significant associated risk factors for T2DM
      included urban residence (AOR 1.23, 95%CI 1.09-1.41), age above 60 years (AOR
      4.77, 95%CI 4.04-5.63), obese BMI (AOR 1.26, 95%CI 1.03-1.55) and central obesity
      (AOR 1.39, 95%CI 1.14-1.68). Compared to indigenous population, individuals of
      Egyptian descents (AOR 1.28, 95%CI 1.04-1.57) and mixed origin (AOR 1.24, 95%CI
      1.04-1.48) had increased risk of T2DM. CONCLUSION: The prevalence of T2DM and
      prediabetes in north Sudan have increased significantly since 1996 with
      variations between ethnicities which showed to be an independent risk factor for
      T2DM. Health authorities are recommended to set plans to meet the health needs of
      these communities.

PMID- 29203256
TI  - Relationship between several surrogate estimates of insulin resistance and a
      direct measure of insulin-mediated glucose disposal: Comparison of fasting versus
      post-glucose load measurements.
AB  - AIMS: The study aim was to determine the correlation of several surrogate
      estimates of insulin resistance with a direct measure of insulin action and the
      ability of these estimates to identify insulin resistant persons. METHODS:
      Retrospective analysis of 454 apparently healthy individuals studied in a
      clinical research center. The correlations between 11 surrogate estimates of
      insulin resistance, using either fasting or post-oral glucose challenge values,
      and a direct measure of insulin-mediated glucose uptake (SSPG concentration
      during the Insulin Suppression Test) were determined as well as the ability of
      the surrogate estimates to identify insulin resistant individuals. RESULTS: All
      surrogate estimates were significantly (P < .001) correlated with SSPG
      concentrations and successfully identified insulin resistant persons. These
      relationships were of lesser magnitude when estimates were based on fasting data,
      with the exception of the McAuley index-derived from fasting data, but resembling
      post-glucose challenge estimates. Moreover, correlation with SSPG concentration,
      and positive identification of insulin resistance, varied considerably among
      estimates. CONCLUSION: All 11 surrogate estimates of insulin resistance
      significantly correlated with insulin-mediated glucose disposal and identified
      insulin resistant persons with a reasonable degree of sensitivity and
      specificity. For identification of insulin resistant individuals, indices based
      on post-glucose challenge measurements performed better than those based on
      fasting measurements, with the exception of McAuley index. The quantitative
      information derived from this analysis should help investigators select the
      surrogate marker of insulin resistance best suited for their study.

PMID- 29203257
TI  - The contribution of illness perceptions and metacognitive beliefs to anxiety and
      depression in adults with diabetes.
AB  - AIMS: Anxiety and depression are highly prevalent in people with diabetes (PwD).
      The most widely used psychological model to explain anxiety and depression in PwD
      is the Common-Sense Model, which gives a central role to illness perceptions. The
      Self-Regulatory Executive Function (S-REF) model proposes metacognitive beliefs
      are key to understanding the development and maintenance of emotional disorders.
      To test the potential utility of the S-REF model in PwD, the study explored if
      metacognitive beliefs explained additional variance in anxiety and depression
      after controlling for demographic and illness perceptions. METHODS: 614 adults
      with either Type 1 (n = 335) or Type 2 (n = 279) diabetes participated in a cross
      sectional online survey. All participants completed questionnaires on anxiety,
      depression, illness perceptions and metacognitive beliefs. RESULTS: Regression
      analyses showed that metacognitive beliefs were associated with anxiety and
      depression in PwD and explained additional variance in both anxiety and
      depression after controlling for demographics and illness perceptions.
      CONCLUSIONS: This is the first study to demonstrate that metacognitive beliefs
      are associated with anxiety and depression in PwD. The clinical implications of
      the study are illustrated.

PMID- 29203258
TI  - The importance, impact and influence of group clinical supervision for graduate
      entry nursing students.
AB  - This paper will report on an evaluation of group clinical supervision (CS)
      facilitated for graduate entry nursing (GEN) students whilst on clinical
      placement. The literature suggests educational forums which enable GEN students
      to engage in critical dialogue, promote reflective practice and ongoing support
      are an essential element of GEN curricula. The model of supervision employed was
      informed by Proctor's three function interactive CS model and Inskipp and
      Proctor's Supervision Alliance. Both emphasise the normative, formative and
      restorative functions of CS as task areas within an overarching humanistic
      supervisory approach. The three-function model informed the design of a
      questionnaire which intended to measure their importance, impact and influence
      through both structured and open-ended questions. Findings suggest the
      restorative function of supervision is most valued and is facilitated in an
      environment where humanistic principles of non-judgement, empathy and trust are
      clearly present. Also the opportunity to learn from others, consider alternative
      perspectives and question personal assumptions regarding capability and
      confidence are a priority for this student group. It is suggested that the
      restorative function of CS should be prioritised within future developments and
      models which view this function as a key purpose of CS should be explored.

PMID- 29203259
TI  - Multicentre study of patient-reported and clinical outcomes following immediate
      and delayed Autologous Breast Reconstruction And Radiotherapy (ABRAR study).
AB  - BACKGROUND: Timing of autologous breast reconstruction in patients requiring
      adjuvant radiotherapy remains contentious. The primary objective of this study
      was to assess clinical and patient reported outcomes in immediate reconstruction
      with radiotherapy compared to delayed reconstruction after radiotherapy, the two
      relevant clinical pathways for patients who need radiotherapy. METHODS: This
      retrospective UK multi-centre study grouped patients into three categories:
      immediate reconstruction with post-operative radiotherapy (IBR); delayed
      reconstruction after radiotherapy (DBR); control group of immediate
      reconstruction without radiotherapy (noRT). Data collection utilised clinician
      questionnaire, patient questionnaire (BreastQ) and medical examination.
      Examination assessed fat necrosis, texture, symmetry and overall result. RESULTS:
      412 patients were recruited (IBR 104; DBR 119; noRT 189) with median follow-up
      time of 57 months. Post-operative complications were higher in IBR & noRT (p
      <0.001). Total number of operations for completion of reconstruction was similar
      in all groups. Completion of reconstruction after mastectomy was three years
      longer in DBR versus IBR. BreastQ domain scores were lower in IBR versus DBR and
      noRT (p <0.01) but all scores were within acceptable range (satisfaction with
      outcome: IBR 71; DBR 85; noRT 81). Examination scores were similar for IBR and
      DBR but lower than noRT (p <0.01). Correlation between BreastQ and examination
      scores was poor. CONCLUSIONS: Acceptable results are observed with either IBR or
      DBR, with high rates of patient and clinician satisfaction, low rates of
      complications, and a similar number of operations to complete reconstruction in
      all groups suggesting all options should be considered for patients.

PMID- 29203260
TI  - The Helsinki Face Transplantation: Surgical aspects and 1-year outcome.
AB  - BACKGROUND: Since 2005, at least 38 facial transplantations have been performed
      worldwide. We herein describe the surgical technique and 1-year clinical outcome
      in Finland's first face transplant case. METHODS: A 34-year-old male who had a
      severe facial deformity following ballistic trauma in 1999 underwent facial
      transplantation at the Helsinki University Hospital on 8th February 2016. Three
      dimensional (3D) technology was used to manufacture donor and recipient patient
      specific osteotomy guides and a donor face mask. The facial transplant consisted
      of a Le Fort II maxilla, central mandible, lower 2/3 of the midface muscles,
      facial and neck skin, oral mucosa, anterior tongue and floor of mouth muscles,
      facial nerve (three bilateral branches), and bilateral hypoglossal and buccal
      nerves. RESULTS: At 1-year follow-up, there have thus far been no clinical or
      histological signs of rejection. The patient has a good aesthetic outcome with
      symmetrical restoration of the mobile central part of the face, with recovery of
      pain and light touch sensation to almost the entire facial skin and intraoral
      mucosa. Electromyography at 1 year has confirmed symmetrical muscle activity in
      the floor of the mouth and facial musculature, and the patient is able to produce
      spontaneous smile. Successful social and psychological outcome has also been
      observed. Postoperative complications requiring intervention included early
      (nasopalatinal fistula, submandibular sialocele, temporomandibular joint pain and
      transient type 2 diabetes) and late (intraoral wound and fungal infection, renal
      impairment and hypertension) complications. CONCLUSION: At 1 year, we report an
      overall good functional outcome in Finland's first face transplant.

PMID- 29203261
TI  - Preoperative Computed Tomography-Guided Pulmonary Lesion Marking in Preparation
      for Fluoroscopic Wedge Resection-Rates of Success, Complications, and Pathology
      Outcomes.
AB  - PURPOSE: In this study, we describe our experience of lesion marking with
      fiducial markers (FM) and microcoils (MC) facilitating same-day surgical wedge
      resection, including success rates, pathology outcomes, and complications. We
      also explored patient/nodular characteristics associated with developing
      complications. MATERIALS AND METHODS: An IRB-approved single-institutional
      retrospective study of 136 patients who had 148 pulmonary nodules was conducted.
      All patients had CT-guided pulmonary nodule labeling with either FM (121) or MC
      (15) patients with plan for same-day fluoroscopic-guided wedge resection.
      RESULTS: Of 136 (98%) patients, 133 had successful same-day wedge resection as
      planned; 2 had delayed but successful wedge resection surgery due to
      complications at the time of marker placement (fiducial embolization and
      hemorrhage/pneumothorax, respectively). A third patient ultimately needed
      lobectomy due to deep lesion location. Eighty percent [118/148] of resected
      nodules were malignant. Further, 68% of the total group of patients [93/136] had
      mild complications of various types including hemorrhage [44/136, 32%],
      pneumothorax [35/136, 26%], a combination of both hemorrhage and pneumothorax
      [10/136, 7%], or migration/embolization [4/136, 3%]. Depth of nodule from skin (P
      = 0.011) and pleura (P = 0.027) was significantly associated with complications.
      CONCLUSION: CT-guided marking of small or deep pulmonary lesions using either
      fiducial markers or microcoils provides an effective means to aid surgeons to
      accomplish minimally invasive wedge resection. The importance of the success of
      this technique is supported by the high incidence (80%) of malignant lesion
      etiology found at postresection pathology. Although complications occurred, the
      vast majority were mild and did not alter planned same-day resection.

PMID- 29203262
TI  - Computed Tomography Coronary Angiography for Evaluation of Children With Kawasaki
      Disease.
AB  - OBJECTIVE: We sought to assess the feasibility of computed tomography coronary
      angiography (CTCA) on a 128-slice, dual source scanner in children with acute and
      convalescent phase Kawasaki disease (KD). MATERIALS AND METHODS: A prospective
      study of 49 children with KD (12 at presentation and 37 in the convalescent
      phase) was conducted between November 2013 and April 2015. CTCA was performed
      with either prospective (n = 37) or retrospective (n = 12) electrocardiographic
      gating. A radiologist blinded to clinical profile and echocardiogram evaluated
      each scan. RESULTS: Median age (36 boys and 13 girls) was 7 years. Median dose
      length product value and median effective CT radiation dose was 32mGycm
      (interquartile range [IQR]: 21-74) and 0.54 miliSieverts (mSv) (IQR: 0.77-3.2)
      for all scans, and 27mGycm (IQR: 18.5-33.75) and 0.48mSv (IQR: 0.18-1.17) for
      prospectively triggered scans (n = 37). Fourteen subjects (30 coronary segments)
      showed abnormalities by CTCA including aneurysms (n = 27) and stenoses (n = 3).
      In the acute phase (n = 12), aneurysms were detected in 5 children (18 segments).
      CONCLUSION: CTCA allows comprehensive evaluation of coronary arteries in children
      with KD.

PMID- 29203263
TI  - Use of Shoulder Imaging in the Outpatient Setting: A Pilot Study.
AB  - PURPOSE: Characterize the clinical utility of diagnostic shoulder imaging
      modalities commonly used in the outpatient workup of shoulder pain.
      MATERIALS/METHODS: Retrospective review of adults imaged for outpatient shoulder
      pain from 1/1/2013 to 9/1/2015. To be categorized as "useful", a study had to
      meet one of the following criteria: change the clinical diagnosis or treatment
      plan, provide a final diagnosis, or guide definitive treatment. A utility score
      was assigned to each study based on the number of utility criteria met (range 0
      4). A score of 1 was considered low utility; a score of greater than or equal to
      2 was considered high utility. Statistical analysis included binary logistic
      regression and generalized estimating equations. RESULTS: 210 subjects (65%
      male); mean age 47 (range 18-84), underwent 302 imaging studies (159 X-ray, 137
      MRI, 2 CT, 4 ultrasound) during the study period. 92.1% of all studies met
      minimum criteria for utility (score >1). Most commonly, diagnostic studies
      obtained during the outpatient workup of shoulder pain were found to guide
      definitive treatment (70.5%) or provide a final diagnosis (53%). Most X-rays were
      categorized as no or low utility (85.5%). 97.8% of the MRI studies were
      categorized as useful with most being high utility (73%). Overall, MRI was the
      most useful modality in all clinical scenarios (P = 0.002) and more likely to be
      high utility (P < 0.001) compared to X-rays. None of the investigated patient or
      injury characteristics were significant predictors of useful imaging. CONCLUSION:
      Our study suggests that both radiographs and MRI are useful in the evaluation of
      adult unilateral shoulder pain in the outpatient setting. MRI appears to be the
      most useful imaging modality in terms of helping guide diagnosis and treatment
      selection. This serves as a potential first step towards the development of
      evidence based imaging algorithms that can be used and tested in future studies.

PMID- 29203264
TI  - Identification of genes regulating GABAergic interneuron maturation.
AB  - During embryonic development, GABAergic interneurons, a main inhibitory component
      in the cerebral cortex, migrate tangentially from the ganglionic eminence (GE) to
      cerebral cortex. After reaching the cerebral cortex, they start to extend their
      neurites for constructing local neuronal circuits around the neonatal stage.
      Aberrations in migration or neurite outgrowth are implicated in neurological and
      psychiatric disorders such as epilepsy, schizophrenia and autism. Previous
      studies revealed that in the early phase of cortical development the neural
      population migrates tangentially from the GE in the telencephalon and several
      genes have been characterized as regulators of migration and specification of
      GABAergic interneurons. However, much less is known about the molecular
      mechanisms of GABAergic interneurons-specific maturation at later stages of
      development. Here, we performed genome-wide screening to identify genes related
      to the later stage by flow cytometry based-microarray (FACS-array) and identified
      247 genes expressed in cortical GABAergic interneurons. Among them, Dgkg, a
      member of diacylglycerol kinase family, was further analyzed. Correlational
      analysis revealed that Dgkg is dominantly expressed in somatostatin (SST)
      expressing GABAergic interneurons. The functional study of Dgkg using GE neurons
      indicated alteration in neurite outgrowth of GABAergic neurons. This study shows
      a new functional role for Dgkg in GABAergic interneurons as well as the
      identification of other candidate genes for their maturation.

PMID- 29203265
TI  - A low blood copper concentration is a co-morbidity burden factor in Parkinson's
      disease development.
AB  - Parkinson's disease (PD) patients are often characterized by copper
      dyshomeostasis, which is responsible for ROS formation and fibrillogenesis.
      However, the relationships between copper metabolism and PD development are
      unclear. In this study in 50 patients with PD (pPD) and 50 age-matched healthy
      individuals, the serum total copper concentration, oxidase activity,
      ceruloplasmin and SOD3 protein concentrations were measured; and amount of copper
      atoms per ceruloplasmin molecule was calculated. These parameters were lower in
      pPD relatively to healthy volunteers. Decrease in concentrations of SOD3,
      ceruloplasmin, and copper but increase of interleukin-6 levels were associated
      with a risk of PD. Two consistent patterns were identified. First, a low serum
      copper concentration related with PD development and predominantly affected the
      non-motor symptoms of PD. There was no correlation between copper concentration
      and ceruloplasmin oxidase activity level (r = 0.27) in pPD. Second, Chelex 100
      treatment revealed that pPD ceruloplasmin compared with ceruloplasmin of healthy
      individuals displayed smaller content of labile copper atoms. The presence or
      absence of these atoms had no effect on ceruloplasmin enzymatic activities. Our
      findings suggest that cuproenzyme deficiency, which is typical for PD, can be
      caused by violation of metabolic incorporation of the labile copper atoms into
      ceruloplasmin molecule.

PMID- 29203266
TI  - Addiction: A multi-determined chronic disease.

PMID- 29203267
TI  - The significance of diminished sTWEAK and P-selectin content in platelets of
      patients with pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterized by
      proliferative changes in pulmonary arteries. There is growing evidence suggesting
      that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P
      selectin could be involved in PAH development and progression. Here we
      investigate whether circulating platelets may be a source of sTWEAK and
      contribute to diminished availability of sTWEAK and P-selectin in PAH patients.
      We have prospectively enrolled two independent study groups of stable patients
      with confirmed PAH and age matched controls: derivation (10 PAH; 15 controls) and
      validation (20 PAH; 12 controls). P-selectin and sTWEAK concentrations were
      measured in platelet-poor plasma and platelet lysate. To avoid procedural bias,
      in each group we employed different protocols for platelet isolation.
      Consistently, both in derivation and validation groups PAH patients presented
      significantly lower sTWEAK content in platelets than control group with no
      significant differences in plasma levels. Similarly, patients presented
      comparable to controls plasma P-selectin concentrations and lower concentration
      in platelet lysate. Kaplan-Meier analysis revealed that patients with low
      platelet sTWEAK/total protein concentration ratio had more frequently detoriation
      of PAH in the follow-up (16.51 +/- 3.32 months), log-rank test, p = .03. Patients
      diagnosed with pulmonary arterial hypertension present diminished sTWEAK and P
      selectin storage capacity in platelets. Thrombocytes appear to be a major source
      of sTWEAK that could be released upon local injury and its decreased availability
      could have an impact on pathophysiology and prognosis in PAH.

PMID- 29203268
TI  - Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in
      the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.
AB  - PURPOSE: We compared blue light flexible cystoscopy with white light flexible
      cystoscopy for the detection of bladder cancer during surveillance. MATERIALS AND
      METHODS: Patients at high risk for recurrence received hexaminolevulinate
      intravesically before white light flexible cystoscopy and randomization to blue
      light flexible cystoscopy. All suspicious lesions were documented. Patients with
      suspicious lesions were referred to the operating room for repeat white and blue
      light cystoscopy. All suspected lesions were biopsied or resected and specimens
      were examined by an independent pathology consensus panel. The primary study end
      point was the proportion of patients with histologically confirmed malignancy
      detected only with blue light flexible cystoscopy. Additional end points were the
      false-positive rate, carcinoma in situ detection and additional tumors detected
      only with blue light cystoscopy. RESULTS: Following surveillance 103 of the 304
      patients were referred, including 63 with confirmed malignancy, of whom 26 had
      carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence
      was seen only with blue light flexible cystoscopy (p <0.0001). Five of these
      cases were confirmed as carcinoma in situ. Operating room examination confirmed
      carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue
      light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light
      cystoscopy identified additional malignant lesions in 29 of the 63 patients
      (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None
      of the 12 adverse events during surveillance were serious. CONCLUSIONS: Office
      based blue light flexible cystoscopy significantly improves the detection of
      patients with recurrent bladder cancer and it is safe when used for surveillance.
      Blue light cystoscopy in the operating room significantly improves the detection
      of carcinoma in situ and detects lesions that are missed with white light
      cystoscopy.

PMID- 29203269
TI  - Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk
      Stratification, Shared Decision Making, and Care Options.
AB  - PURPOSE: This guideline is structured to provide a clinical framework stratified
      by cancer severity to facilitate care decisions and guide the specifics of
      implementing the selected management options. The summary presented represents
      Part I of the two-part series dedicated to Clinically Localized Prostate Cancer:
      AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer
      severity. MATERIALS AND METHODS: The systematic review utilized in the creation
      of this guideline was completed by the Agency for Healthcare Research and Quality
      and through additional supplementation by ECRI Institute. This review included
      articles published between January 2007 and March 2014 with an update search
      conducted through August 2016. When sufficient evidence existed, the body of
      evidence for a particular treatment was assigned a strength rating of A (high), B
      (moderate), or C (low) for support of Strong, Moderate, or Conditional
      Recommendations. Additional information is provided as Clinical Principles and
      Expert Opinions (table 2 in supplementary unabridged guideline,
      http://jurology.com/). RESULTS: The AUA (American Urological Association), ASTRO,
      and SUO (Society of Urologic Oncology) formulated an evidence-based guideline
      based on a risk stratified clinical framework for the management of localized
      prostate cancer. CONCLUSIONS: This guideline attempts to improve a clinician's
      ability to treat patients diagnosed with localized prostate cancer, but higher
      quality evidence in future trials will be essential to improve the level of care
      for these patients. In all cases, patient preferences should be considered when
      choosing a management strategy.

PMID- 29203270
TI  - B-1 cells upregulate CD8 T lymphocytes and increase proinflammatory cytokines
      serum levels in oral encephalitozoonosis.
AB  - Microsporidia are intracellular pathogens that cause severe disease in
      immunocompromised humans and animals. We recently demonstrated that XID mice are
      more susceptible to Encephalitozoon cuniculi infection by intraperitoneal route,
      evidencing the role of B-1 cells in resistance against infection. The present
      study investigated the resistance and susceptibility against E. cuniculi oral
      infection, including the role of B-1 cells. BALB/c and BALB/c XID (B-1 cells
      deficient) mice were orally infected with E. cuniculi spores. No clinical
      symptoms were observed in infected animals; histopathology showed
      lymphoplasmocytic enteritis with degeneration of the apexes of the villi in all
      infected groups. Higher parasite burden was observed in infected BALB/c XID mice.
      In the spleen and peritoneum, all infected mice showed a decrease of lymphocytes,
      including CD8+ T cells, mostly in infected BALB/c XID mice. Adoptive transfer of
      B-1 cells (XID + B-1) was associated with a lower parasite burden. Pro
      inflammatory cytokines (IFN-gamma, TNF-alpha and IL-6) increased mostly in
      infected XID + B1 mice. Together, the present results showed that BALB/c XID mice
      infected by the oral route were more susceptible to encephalitozoonosis than
      BALB/c mice, demonstrating the B-1 cells importance in the control of the immune
      response against oral E. cuniculi infection.

PMID- 29203272
TI  - Comparison of the inducible effects of licorice products with or without heat
      processing and pre-treatment with honey on granulocyte colony-stimulating factor
      secretion in cultured enterocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (the roots and rhizomes of Glycyrrhiza
      uralensis Fisch.) is occasionally used as crude drug following processing
      including roasting or honey-roasting (soaking with honey before roasting) in
      traditional Japanese Kampo medicine and traditional Chinese medicine (TCM). AIM
      OF THE STUDY: We investigated the differences in the inducible effect of
      processed licorice products on granulocyte colony-stimulating factor (G-CSF)
      secretion in cultured intestinal epithelial cells and elucidated the active
      ingredients in both unprocessed and processed licorice products. MATERIALS AND
      METHODS: We prepared heat-processed licorice with or without pretreatment with
      honey, and fractionated the extracts by Sephadex G-100. Enterocyte-like
      differentiated MCE301 cells were incubated in media comprising a hot water
      extract of licorice products for 24h, and the concentrations of G-CSF in the
      media were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Licorice extract induced G-CSF secretion in MCE301 cells, and the active
      ingredients of licorice were high molecular compounds. Although the roasted
      licorice extract exhibited the activity similar to that of the unprocessed
      licorice extract, honey-roasted licorice extracts exhibited a significantly
      higher inducible effect on G-CSF secretion in the cells than that of unprocessed
      or roasted licorice extracts without pretreatment with honey. This enhanced
      activity was dependent on the temperature and heating time. CONCLUSIONS: The
      enhanced inducible effect of honey-roasted licorice on G-CSF secretion might be
      attributed to the combined effect of licorice-derived high molecular compounds
      and heated-honey-derived compounds. The results of this study can scientifically
      explain the objective of processing via honey-roasting in TCM theory.

PMID- 29203271
TI  - Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane
      targeting.
AB  - For decades oncogenic RAS proteins were considered undruggable due to a lack of
      accessible binding pockets on the protein surfaces. Seminal early research in RAS
      biology uncovered the basic paradigm of post-translational isoprenylation of RAS
      polypeptides, typically with covalent attachment of a farnesyl group, leading to
      isoprenyl-mediated RAS anchorage at the plasma membrane and signal initiation at
      those sites. However, the failure of farnesyltransferase inhibitors to translate
      to the clinic stymied anti-RAS therapy development. Over the past ten years, a
      more complete picture has emerged of RAS protein maturation, intracellular
      trafficking, and location, positioning and retention in subdomains at the plasma
      membrane, with a corresponding expansion in our understanding of how these
      properties of RAS contribute to signal outputs. Each of these aspects of RAS
      regulation presents a potential vulnerability in RAS function that may be
      exploited for therapeutic targeting, and inhibitors have been identified or
      developed that interfere with RAS for nearly all of them. This review will
      summarize current understanding of RAS membrane targeting with a focus on
      highlighting development and outcomes of inhibitors at each step.

PMID- 29203274
TI  - The effect of a modular education program for children with epilepsy and their
      parents on disease management.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy of Modular
      Education Program for Children with Epilepsy and Their Parents on disease
      management. The program was prepared by researchers in an interdisciplinary team.
      METHOD: Children with epilepsy and their parents were included in a randomized
      controlled study using a pre-posttest design. All participants of the modular
      education program (n=184 (92 children and their 92 parents')) answered a lot of
      scales immediately before the program. The researcher presented the modular
      education program, which included eight modules (four for the children and four
      for the parents), to the children and parents in the intervention group using
      interactive teaching methods. And all participants of the modular education
      program answered all scales immediately after the program and one-month, three
      month follow-ups. The control group not participating in the modular education
      program (n=100 (50 children, 50 parents)) also answered all scales in all follow
      ups. Scales used the study comprised epilepsy-specific outcome measures (e.g.,
      knowledge, self-efficacy related to seizures, quality of life and anxiety). The
      statistical analyses of the study data were performed using SAS 9.3 software.
      RESULTS: Children in intervention group significantly improved in knowledge
      (p<0.001), self-efficacy about seizures (p<0.001), and quality of life (p<0.001)
      compared with the control group. The parents in the intervention group also
      significantly improved in knowledge about epilepsy (p<0.001) compared with the
      control group. However, anxiety of the parents in the intervention group
      significantly increased (p<0.001). CONCLUSION: The efficacy of the Modular
      Education Program for Children with Epilepsy and Their Parents on disease
      management was confirmed. The results indicate that using interactive teaching
      methods help children with epilepsy and their parents in improving knowledge,
      self-efficacy about seizures and quality of life. All health professionals who
      work with children with epilepsy and their parents should provide these modular
      education programs regularly.

PMID- 29203273
TI  - The traditional use of Vachellia nilotica for sexually transmitted diseases is
      substantiated by the antiviral activity of its bark extract against sexually
      transmitted viruses.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Vachellia (Acacia) nilotica and other plants of
      this genus have been used in traditional medicine of Asian and African countries
      to treat many disorders, including sexually transmitted diseases, but few studies
      were performed to validate their anti-microbial and anti-viral activity against
      sexually transmitted infections. AIM OF THE STUDY: The present study was
      undertaken to explore whether the ethnomedical use of V.nilotica to treat genital
      lesions is substantiated by its antiviral activity against the human
      immunodeficiency virus (HIV), the herpes simplex virus (HSV) and the human
      papillomavirus (HPV). MATERIALS AND METHODS: The antiviral activity of V.nilotica
      was tested in vitro by virus-specific inhibition assays using HSV-2 strains,
      sensible or resistant to acyclovir, HIV-1IIIb strain and HPV-16 pseudovirion
      (PsV). The potential mode of action of extract against HSV-2 and HPV-16 was
      further investigated by virus inactivation and time-of-addition assays on cell
      cultures. RESULTS: V.nilotica chloroform, methanolic and water bark extracts
      exerted antiviral activity against HSV-2 and HPV-16 PsV infections; among these,
      methanolic extract showed the best EC50s with values of 4.71 and 1.80ug/ml
      against HSV-2 and HPV-16, respectively, and it was also active against an
      acyclovir-resistant HSV-2 strain with an EC50 of 6.71ug/ml. By contrast, no
      suppression of HIV infection was observed. Investigation of the mechanism of
      action revealed that the methanolic extract directly inactivated the infectivity
      of the HPV-16 particles, whereas a partial virus inactivation and interference
      with virus attachment (EC50 of 2.74ug/ml) were both found to contribute to the
      anti-HSV-2 activity. CONCLUSIONS: These results support the traditional use of
      V.nilotica applied externally for the treatment of genital lesions. Further work
      remains to be done in order to identify the bioactive components.

PMID- 29203275
TI  - Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment
      options and future research directions.
AB  - Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred
      years. However, its exact pathomechanisms are still incompletely understood and
      there is no specific therapy available so far. In this systematic review, studies
      published between January 2000 and July 2017 involving pathomechanisms and
      experimental treatments of SM-induced skin lesions were analyzed to summarize
      current knowledge on SM pathology, to provide an overview on novel treatment
      options, and to identify promising targets for future research to more
      effectively counter SM effects. We suggest that future studies should focus on
      (I) systemic effects of SM intoxication due to its distribution throughout the
      body, (II) removal of SM depots that continuously release active compound
      contributing to chronic skin damage, and (III) therapeutic options that
      counteract the pleiotropic effects of SM.

PMID- 29203276
TI  - Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism.
AB  - The use of diclofenac is associated with rare but severe drug-induced liver
      injury (DILI) in a very small number of patients. The factors which predispose
      susceptible patients to hepatotoxicity of diclofenac are still incompletely
      understood. Formation of protein-reactive metabolites by UDP-glucuronosyl
      transferases and cytochromes P450 is commonly considered to play an important
      role, as indicated by the detection of covalent protein adducts and antibodies in
      the serum of patients suffering from diclofenac-induced liver injury. Since no
      associations have been found with HLA-alleles, polymorphisms of genes encoding
      for proteins involved in the disposition of diclofenac may be important. Previous
      association studies showed that possession of the UGT2B7*2 and CYP2C8*4 alleles
      is more common in cases of diclofenac-induced DILI. In the present study, the
      metabolism of diclofenac by UGT2B7*2 and CYP2C8*4 was compared with their
      corresponding wild-type enzymes. Enzyme kinetic analysis revealed that
      recombinant UGT2B7*2 showed an almost 6-fold lower intrinsic clearance of
      diclofenac glucuronidation compared to UGT2B7*1. The mutant CYP2C8*4 showed
      approximately 35% reduced activity in the 4'-hydroxylation of diclofenac acyl
      glucuronide. Therefore, a decreased hepatic exposure to diclofenac acyl
      glucuronide is expected in patients with the UGT2B7*2 genotype. The increased
      risk for hepatotoxicity, therefore, might be the result from a shift to oxidative
      bioactivation to cytotoxic quinoneimines.

PMID- 29203277
TI  - Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat
      cells.
AB  - Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to
      increase oxidative stress by altering membrane ion permeability and uncoupling
      oxidative phosphorylation. A toxicogenomic study was performed to investigate
      gene expression changes triggered by BEA exposure (1.5, 3 and 5 MUM; 24 h) in
      Jurkat cells through RNA-sequencing and differential gene expression analysis.
      Perturbed gene expression was observed in a concentration dependent manner, with
      43 differentially expressed genes (DEGs) overlapped in the three studied
      concentrations. Gene ontology (GO) analysis showed several biological processes
      related to electron transport chain, oxidative phosphorylation, and cellular
      respiration significantly altered. Molecular functions linked to mitochondrial
      respiratory chain and oxidoreductase activity were over-represented (q-value <
      0.01). Pathway analysis revealed oxidative phosphorylation and electron transport
      chain as the most significantly altered pathways in all studied doses (z-score >
      1.96; adj p-value < 0.05). 77 genes involved in the respiratory chain were
      significantly down-regulated at least at one dose. Moreover, 21 genes related to
      apoptosis and programmed cell death, and 12 genes related to caspase activity
      were significantly altered, mainly affecting initiator caspases 8, 9 and 10. The
      results demonstrated BEA-induced mitochondrial damage affecting the respiratory
      chain, and pointing to apoptosis through the caspase cascade in human
      lymphoblastic T cells.

PMID- 29203278
TI  - Importance of tau in cognitive decline as revealed by developmental exposure to
      lead.
AB  - Previous reports by us have determined that developmental exposure to the heavy
      metal lead (Pb) resulted in cognitive impairment in aging wildtype mice, and a
      latent induction in biomarkers associated with both the tau and amyloid pathways.
      However, the relationship between these two pathways and their correlation to
      cognitive performance needs to be scrutinized. Here, we investigated the impact
      of developmental Pb (0.2%) exposure on the amyloid and tau pathways in a
      transgenic mouse model lacking the tau gene. Cognitive function, and levels of
      intermediates in the amyloid and tau pathways following postnatal Pb exposure
      were assessed on young adult and mature transgenic mice. No significant
      difference in behavioral performance, amyloid precursor protein (APP), or amyloid
      beta (Abeta) levels was observed in transgenic mice exposed to Pb. Regulators of
      the tau pathway were impacted by the absence of tau, but no additional change was
      imparted by Pb exposure. These results revealed that developmental Pb exposure
      does not cause cognitive decline or change the expression of the amyloid pathway
      in the absence of tau. The essentiality of tau to mediate cognitive decline by
      environmental perturbations needs further investigation.

PMID- 29203279
TI  - Homeostatic Cell Growth Is Accomplished Mechanically through Membrane Tension
      Inhibition of Cell-Wall Synthesis.
AB  - Feedback mechanisms are required to coordinate balanced synthesis of subcellular
      components during cell growth. However, these coordination mechanisms are not
      apparent at steady state. Here, we elucidate the interdependence of cell growth,
      membrane tension, and cell-wall synthesis by observing their rapid re
      coordination after osmotic shocks in Gram-positive bacteria. Single-cell
      experiments and mathematical modeling demonstrate that mechanical forces dually
      regulate cell growth: while turgor pressure produces mechanical stress within the
      cell wall that promotes its expansion through wall synthesis, membrane tension
      induces growth arrest by inhibiting wall synthesis. Tension inhibition occurs
      concurrently with membrane depolarization, and depolarization arrested growth
      independently of shock, indicating that electrical signals implement the negative
      feedback characteristic of homeostasis. Thus, competing influences of membrane
      tension and cell-wall mechanical stress on growth allow cells to rapidly correct
      for mismatches between membrane and wall synthesis rates, ensuring balanced
      growth.

PMID- 29203280
TI  - Reduced post-stroke glial scarring in the infant primate brain reflects age
      related differences in the regulation of astrogliosis.
AB  - Ischemic stroke remains a leading cause of disability worldwide. Surviving
      patients often suffer permanent neurological impairments, and spontaneous
      recovery rarely occurs. However, observations that early-life brain injuries,
      including strokes, elicit less severe long-term functional impairments, compared
      to adults, continue to intrigue. While much research has focussed on neuronal
      changes and plasticity, less is known regarding the regulation of astrogliosis
      and glial scar formation after a stroke at different stages of life. Therefore,
      we investigated the cellular, molecular and temporal differences in chronic scar
      development in the infant and adult nonhuman primate (NHP) post-stroke as it
      bears greater clinical relevance in the close temporal and pathophysiological
      homology with humans. This project utilized the endothelin-1 model of focal
      ischemic stroke in the infant and adult primary visual cortex and investigated
      differences in the subacute and chronic period. We report here that the post
      stroke infant neocortex generates a smaller, more discrete chronic scar,
      correlating to greater neuronal sparing. Reactive astrocytes that comprise the
      chronic scar are generated earlier in infants compared to adults, and the
      expression of critical markers of astrocyte reactivity differs in the subacute
      period between post-stroke infants and adults. Most importantly, we report that
      unlike adults, infant astrocyte reactivity is not dependent on several crucial
      regulators: signal transducer and activator of transcription 3, lipocalin2 and
      collagen I. Our results demonstrate that infant reactive astrocytes are not
      regulated by the same intrinsic and extrinsic factors that control these
      processes in adults, resulting in a more discrete chronic glial scar that is more
      permissible to neuronal sparing.

PMID- 29203282
TI  - Modulation of Mcl-1 transcription by serum deprivation sensitizes cancer cells to
      cisplatin.
AB  - BACKGROUND: The development of approaches that increase therapeutic effects of
      anti-cancer drugs is one of the most important tasks of oncology. Caloric
      restriction in vivo or serum deprivation (SD) in vitro has been shown to be an
      effective tool for sensitizing cancer cells to chemotherapeutic drugs. However,
      the detailed mechanisms underlying the enhancement of apoptosis in cancer cells
      by SD remain to be elucidated. METHODS: Flow cytometry, caspase activity assay
      and western blotting were used for cell death rate evaluation. Western blotting,
      gel-filtration, siRNA approach and qRT-PCR were used to elucidate the mechanism
      underlying cell death potentiation upon SD. RESULTS: We demonstrated that SD
      sensitizes cancer cells to treatment with chemotherapeutic agent cisplatin. This
      effect is independent on activation of caspases-2 and -8, apical caspases
      triggering apoptosis in response to genotoxic stress. SD potentiates cell death
      via downregulation of the anti-apoptotic protein Mcl-1. In fact, SD reduces the
      Mcl-1 mRNA level, which consequently decreases the Mcl-1 protein level and
      renders cells more susceptible to apoptosis induction via the formation of
      apoptosome. CONCLUSIONS: Mcl-1 protein is an important regulator of sensitivity
      of cancer cells to apoptotic stimuli upon SD. GENERAL SIGNIFICANCE: This study
      identifies Mcl-1 as a new target for the sensitization of human cancer cells to
      cell death by SD, which is of great significance for the development of efficient
      anti-cancer therapies.

PMID- 29203281
TI  - Bliverdin reductase-A improves neurological function in a germinal matrix
      hemorrhage rat model.
AB  - Germinal matrix hemorrhage is induced by stereotaxic injection of collagenase
      into the germinal matrix of P7 Sprague-Dawley rats. Hemoglobin assay, western
      blot, immunofluorescence and neurobehavioral tests were used to test the effects
      of BLVRA on hematoma resolution and anti-inflammatory response. We showed that
      BLVRA triggered a signaling cascade that ameliorated post-hemorrhagic
      neurological deficits in both short-term and long-term neurobehavioral tests in a
      GMH rat model. Specifically, BLVRA inhibited toll-like receptor 4 (TLR4)
      expression by translocating to the nucleus in an endothelial nitric oxide
      (eNOS)/nitric oxide (NO)-dependent manner. BLVRA also induced the upregulation of
      CD36 scavenger receptor level in microglia/microphages, of which the prominent
      role is to enhance hematoma resolution. However, the beneficial effects of BLVRA
      were abolished with the knockdown of eNOS, indicating that the eNOS/NO system is
      an important downstream factor of BLVRA. Our results demonstrate a mechanism of
      BLVRA modulating hematoma resolution and suppressing inflammation through
      eNOS/NO/TLR4 pathway in the GMH rat model.

PMID- 29203283
TI  - Understanding the structural and energetic basis of PD-1 and monoclonal
      antibodies bound to PD-L1: A molecular modeling perspective.
AB  - BACKGROUND: The inhibitors blocking the interaction between programmed cell death
      protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune
      response of T cell and eliminate cancer cells. The crystallographic studies have
      provided structural insights of the interactive interfaces between PD-L1 and its
      protein ligands. However, the hotspot residues on PD-L1 as well as structural and
      energetic basis for different protein ligands still need to be further
      investigated. METHODS: Molecular modeling methods including molecular dynamics
      simulation, per-residue free energy decomposition, virtual alanine scanning
      mutagenesis and residue-residue contact analysis were used to qualitatively and
      quantitatively analyze the interactions between PD-L1 and different protein
      ligands. RESULTS: The results of virtual alanine scanning mutagenesis suggest
      that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The
      residue-residue contact analysis further shows that PD-1 interacts with PD-L1
      mainly by F and G strands while monoclonal antibodies like avelumab and BMS
      936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain.
      CONCLUSIONS: A structurally similar beta-hairpin peptide with 13 or 14 residues
      was extracted from each protein ligand and these beta-hairpin peptides were found
      tightly binding to the putative hotspot residues on PD-L1. GENERAL SIGNIFICANCE:
      This study recognizes the hotspot residues on PD-L1 and uncovers the common
      structural and energetic basis of different protein ligands binding to PD-L1.
      These results will be valuable for the design of small molecule or peptide
      inhibitors targeting on PD-L1.

PMID- 29203284
TI  - Intermediate-term survival and quality of life outcomes in patients with advanced
      colorectal liver metastases undergoing associating liver partition and portal
      vein ligation for staged hepatectomy.
AB  - BACKGROUND: Associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) is an innovative, 2-staged hepatectomy which has elicited
      controversy within the international hepatobiliary community. Uptake of ALPPS has
      been limited due to concerns related to evidence of high morbidity and mortality,
      and scant oncologic and outcome data on quality of life (Qol). Demonstrating
      reasonable long-term benefits with a short-term risk is necessary to support more
      widespread endorsement of ALPPS. Our aim was to describe the intermediate-term
      survival and patient-reported quality of life outcomes after an ALPPS. METHODS:
      Prospectively collected data from 2 high-volume ALPPS centers, who were pioneers
      with the technique, were combined and analyzed for disease-free and overall
      survival from date of the ALLPS. Only patients treated for colorectal liver
      metastases with >6 month postoperative follow-up were included. All patients had
      bilateral colorectal liver metastases with an initially unresectable tumor load,
      and received preoperative chemotherapy. Information concerning the demographics
      of the patients, characteristics of the tumor, and treatment were analyzed. The
      well-validated European Organization for Research and Treatment for Cancer
      Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess
      patient quality of life. RESULTS: A total of 58 patients underwent ALPPS for
      colorectal liver metastases, and 47 patients met our inclusion criteria. There
      were no perioperative mortalities, and the rate of severe complications was 21%.
      At 3 years post-ALPPS, the overall survival was 50%, while the disease-free
      survival was 13%. The commonest site of first recurrence was the liver alone
      (38%). Patient-reported quality of life after ALPPS was similar to reference
      values for general population. CONCLUSION: In select patients operated at
      experienced centers, ALPPS results in low perioperative risk, satisfactory
      overall survival, and excellent quality of life. Hepatic recurrence and not
      systemic recurrence is the most common site of relapse after ALPPS.

PMID- 29203285
TI  - Retroperitoneal sarcomas: does the center really matter?

PMID- 29203286
TI  - An opportunity for improvement in trauma care: 8-week booster vaccination
      adherence among patients after trauma splenectomy.
AB  - BACKGROUND: Splenectomies are common after abdominal trauma, and measures must be
      taken to prevent infection, namely, the administration of available conjugate
      vaccinations against encapsulated organisms. While initial immunization is
      frequently completed prior to discharge, the Advisory Council on Immunization
      Practices recommends administration of an 8-week vaccination booster against S.
      pneumoniae, and compliance with this practice is unknown. We hypothesized that
      patients undergoing splenectomy for trauma would not routinely receive the
      recommended immunization and subsequent booster. METHODS: All trauma admissions
      at our center who required splenectomy secondary to trauma between 2010 and 2015
      were included. Demographic and injury data, splenectomy dates, immunization
      documentation, subsequent boosters received, and outcomes were collected from the
      medical record. RESULTS: Of the 9,965 patients observed, 44 patients underwent
      splenectomy, with 31 patients meeting inclusion/exclusion criteria. Two patients
      received subsequent boosters during office or hospital visits; however, no
      patient received any booster within Advisory Council on Immunization Practices'
      recommended timeframe with median time to subsequent boosters of 22 months. Seven
      patients have had a subsequent admission for infection or sepsis, with one
      presenting with S. pneumoniae meningitis. None of the patients subsequently
      admitted for infection or sepsis had received boosters. CONCLUSION: While trauma
      patients at our institution receive recommended immunizations after splenectomy
      prior to discharge, they receive boosters at a suboptimal rate and beyond the
      advised timeframe. We speculate that this phenomenon is widespread in the
      American trauma population. These data suggest a need for improved patient and
      provider education and coordination with primary care practitioners to ensure
      ideal defense against infectious complications.

PMID- 29203287
TI  - Effects of endurance training on serum lipids.
AB  - BACKGROUND AND AIMS: Physical activity is recommended as part of the lifestyle
      modification for the treatment of hyperlipidemia, however, the literature reports
      heterogeneous quantitative effects of exercise on serum lipids. We therefore
      reviewed the effects of aerobic exercise on serum lipids with special focus on
      the training effectiveness. METHODS: Data regarding effects of endurance training
      (ET) on total Cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C)
      and triglycerides (TG) were evaluated in a selective literature search. To
      account for the observed heterogeneity of the training interventions, studies
      were analyzed according to effectiveness (duration, intensity, frequency) of
      training. RESULTS: Unselected training intervention studies did not exert
      significant effects on serum LDL-C but showed minor positive effects on HDL-C and
      TG. Effective endurance training - defined as endurance training performed by an
      intensity of 65-75% of the heart rate reserve (corresponding to 75-85% maximum
      heart rate or 65-80% VO2max) for a duration of 40-50min per training unit on 3
      4days/week over a period of 26-40weeks showed improvement of serum lipids.
      Effective training lowered TC by -3.75% (p=0.0006), LDL-C by -4.76% (p=0.0015),
      TG by -8.24% (p=0.0004) and increased HDL-C by +4.43% (p=0.0061). CONCLUSION: The
      analysis suggests that a minimum exercise threshold is necessary to produce
      effects on serum lipids. Overall, the quantitative effect of physical activity on
      serum lipids is small.

PMID- 29203288
TI  - Veno-arterial extracorporeal membrane oxygenation in a case of amniotic fluid
      embolism with coexisting hemorrhagic shock: lessons learned.

PMID- 29203289
TI  - Time and dose-related changes in lung perfusion after definitive radiotherapy for
      NSCLC.
AB  - BACKGROUND AND PURPOSE: To examine radiation-induced changes in regional lung
      perfusion per dose level in 58 non-small-cell lung cancer (NSCLC) patients
      treated with intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: NSCLC
      patients receiving chemo-radiotherapy (RT) of minimum 60 Gy were included
      prospectively in the study. Lung perfusion single-photon emission computed
      tomography (SPECT/CT) was performed before and serially after RT. Changes
      (relative to baseline, %) in regional lung perfusion were correlated with
      regional dose. Toxicity outcome was radiation pneumonitis (RP) CTC grades 2-5.
      RESULTS: Perfusion changes were associated with dose. Dose-dependent reduction in
      regional perfusion was observed at 3, 6 and 12 months of follow-up. Relative
      perfusion loss per dose bin was 4% at 1 month, 14% at 3 months, 13% at 6 months
      and 21% at 12 months after RT. In patients with RP, perfusion reduction was
      larger in high dose lung regions, compared to those without RP. Low dose regions,
      on the contrary, revealed perfusion gain in the patients with RP. CONCLUSION:
      Progressive dose dependent perfusion loss is manifested on SPECT up to 12 months
      following IMRT. These findings suggest that the dynamic change in perfusion may
      have prognostic value in predicting radiation pneumonitis in NSCLC patients
      treated with IMRT.

PMID- 29203290
TI  - Patterns of locoregional failure in locally advanced non-small cell lung cancer
      treated with definitive conformal radiotherapy: Results from the Gating 2006
      trial.
AB  - PURPOSE: To determine the patterns of locoregional failure (LRF) in patients with
      locally advanced non-small cell lung cancer treated with definitive radiotherapy
      (RT). PATIENTS AND METHODS: One hundred and fifty-four patients from the Gating
      2006 prospective randomized trial were treated with conformal RT with or without
      respiratory motion management. For patients with a LRF as first event, treatment
      planning with simulation CT, pre-treatment 18FDG PET-CT and post-treatment images
      demonstrating recurrence were registered and analyzed. Measurable LRF was
      contoured (rGTV) and classified as in-field, marginal, or out-of-field. RESULTS:
      Median follow-up was 27.8 months. Forty-eight patients presented with LRF. One
      year and 2-year locoregional disease-free survival rates were 77% (95% CI 70-83)
      and 72% (95% CI 64-79) respectively. 79% of the patients with LRF as first event
      relapsed within the RT field (55% isolated), 30% had marginal LRF component.
      Isolated out-of-field failure occurred in only 3% of all patients. The regions of
      highest FDG-uptake on pre-treatment PET-CT were located within the recurrence in
      91% of patients with in-field LRF. CONCLUSION: In-field failure was the most
      common pattern of failure. Escalated dose RT with high-dose fractions guided by
      PET parameters warrants further investigation.

PMID- 29203291
TI  - Independent component analysis for rectal bleeding prediction following prostate
      cancer radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate the benefit of independent component analysis
      (ICA)-based models for predicting rectal bleeding (RB) following prostate cancer
      radiotherapy. MATERIALS AND METHODS: A total of 593 irradiated prostate cancer
      patients were prospectively analyzed for Grade >=2 RB. ICA was used to extract
      two informative subspaces (presenting RB or not) from the rectal DVHs, enabling a
      set of new pICA parameters to be estimated. These DVH-based parameters, along
      with others from the principal component analysis (PCA) and functional PCA, were
      compared to "standard" features (patient/treatment characteristics and DVH bins)
      using the Cox proportional hazards model for RB prediction. The whole cohort was
      divided into: (i) training (N = 339) for ICA-based subspace identification and
      Cox regression model identification and (ii) validation (N = 254) for RB
      prediction capability evaluation using the C-index and the area under the
      receiving operating curve (AUC), by comparing predicted and observed toxicity
      probabilities. RESULTS: In the training cohort, multivariate Cox analysis
      retained pICA and PC as significant parameters of RB with 0.65 C-index. For the
      validation cohort, the C-index increased from 0.64 when pICA was not included in
      the Cox model to 0.78 when including pICA parameters. When pICA was not included,
      the AUC for 3-, 5-, and 8-year RB prediction were 0.68, 0.66, and 0.64,
      respectively. When included, the AUC increased to 0.83, 0.80, and 0.78,
      respectively. CONCLUSION: Among the many various extracted or calculated
      features, ICA parameters improved RB prediction following prostate cancer
      radiotherapy.

PMID- 29203292
TI  - Pitfalls in the detection of citrullination and carbamylation.
AB  - Carbamylation and citrullination are both post-translational modifications
      against which (auto)antibodies can be detected in sera of rheumatoid arthritis
      (RA) patients. Carbamylation is the chemical modification of a lysine into a
      homocitrulline, whereas citrullination is an enzymatic conversion of an arginine
      into a citrulline. It is difficult to distinguish between the two resulting amino
      acids due to similarities in structure. However, differentiation between
      citrulline and homocitrulline is important to understand the antigens that induce
      antibody production and to determine which modified antigens are present in
      target tissues. We have observed in literature that conclusions are frequently
      drawn regarding the citrullination or carbamylation of proteins based on reagents
      that are not able to distinguish between these two modifications. Therefore, we
      have analyzed a wide spectrum of methods and describe here which method we
      consider most optimal to distinguish between citrulline and homocitrulline. We
      have produced several carbamylated and citrullinated proteins and investigated
      the specificity of (commercial) antibodies by both ELISA and western blot.
      Furthermore, detection methods based on chemical modifications, such as the anti
      modified citrulline-"Senshu" method and also mass spectrometry were investigated
      for their capacity to distinguish between carbamylation and citrullination. We
      observed that some antibodies are able to distinguish between carbamylation and
      citrullination, but an overlap in reactivity is often present in the commercially
      available anti-citrulline antibodies. Finally, we conclude that the use of mass
      spectrometry is currently essential to differentiate between citrullinated and
      carbamylated proteins present in complex biological samples.

PMID- 29203293
TI  - Association between prenatal exposure to organochlorine pesticides and the mental
      and psychomotor development of infants at ages 6 and 18 months: The Hokkaido
      Study on Environment and Children's Health.
AB  - Organochlorine pesticides (OCPs) are environmental contaminants that persist in
      the environment and bioaccumulate through the food chain in humans and animals.
      Although previous studies have shown an association between prenatal OCP exposure
      and subsequent neurodevelopment, the levels of OCPs included in these studies
      were inconsistent. A hospital-based prospective birth cohort study was conducted
      to examine the associations between prenatal exposure to relatively low levels of
      OCPs and neurodevelopment in infants at 6 (n=164) and 18 (n=115)months of age.
      Blood samples were analyzed using gas chromatography/mass spectrometry techniques
      to quantify 29 OCPs. The Bayley Scales of Infant Development 2nd edition (BSID
      II) was used to assess the Mental and Psychomotor Developmental Index. After
      controlling for confounders, we found an inverse association between prenatal
      exposure to cis-heptachlor epoxide and the Mental Developmental Index at 18
      months of age. Furthermore, infants born to mothers with prenatal concentrations
      of cis-heptachlor epoxide in the highest quartile had Mental Developmental Index
      scores -9.8 (95% confidence interval: -16.4, -3.1) lower than that recorded for
      infants born to mothers with concentrations of cis-heptachlor epoxide in the
      first quartile (p for trend <0.01). These results support the hypothesis that
      prenatal exposure to OCPs, especially cis-heptachlor epoxide, may have an adverse
      effect on the neurodevelopment of infants at specific ages, even at low levels.

PMID- 29203294
TI  - Subclinical atrial fibrillation: The significance of progression to longer
      episodes.

PMID- 29203295
TI  - Deployment of a Sapien 3 Transcatheter Valve for Severe Tricuspid Insufficiency
      in a Patient With Non-obstructive Cor Triatriatum Dexter.

PMID- 29203296
TI  - LVADs and Infections: How Can We Help?

PMID- 29203297
TI  - Does Statin Reloading Before Cardiac Surgery Improve Postoperative Outcomes?

PMID- 29203298
TI  - The Genetic and Molecular Bases for Hypertrophic Cardiomyopathy: The Role for
      Calcium Sensitization.
AB  - Hypertrophic cardiomyopathy (HCM) affects millions of people around the world as
      one of the most common genetic heart disorders and leads to cardiac ischemia,
      heart failure, dysfunction of other organ systems, and increased risk for sudden
      unexpected cardiac deaths. HCM can be caused by single-point mutations, insertion
      or deletion mutations, or truncation of cardiac myofilament proteins. The
      molecular mechanism that leads to disease progression and presentation is still
      poorly understood, despite decades of investigations. However, recent research
      has made dramatic advances in the understanding of HCM disease development.
      Studies have shown that increased calcium sensitivity is a universal feature in
      HCM. At the molecular level, increased crossbridge force (or power) generation
      resulting in hypercontractility is the prominent feature. Thus, calcium
      sensitization/hypercontractility is emerging as the primary stimulus for HCM
      disease development and phenotypic expression. Cross-bridge inhibition has been
      shown to halt HCM presentation, and myofilament desensitization appears to reduce
      lethal arrhythmias in animal models of HCM. These advances in basic research will
      continue to deepen the knowledge of HCM pathogenesis and are beginning to
      revolutionize the management of HCM.

PMID- 29203299
TI  - Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung
      Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2
      Device.
AB  - OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by
      the PiCCO2 device to assess cardiac index and pulmonary edema during the
      postoperative course after single-lung transplantation. DESIGN: Prospective
      observational study. SETTINGS: Intensive care unit, university hospital (single
      center). PARTICIPANTS: Single-lung transplant patients. INTERVENTIONS: The
      authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter
      and assessed pulmonary edema using extravascular lung water index and pulmonary
      vascular permeability index measured by PiCCO2. MEASUREMENTS AND MAIN RESULTS: A
      Bland-Altman method was used to compare cardiac index measured by PiCCO2 and
      pulmonary artery catheter. Extravascular lung water index and pulmonary vascular
      permeability index were compared according to the PaO2/FiO2 ratio with a
      threshold value of 150 mmHg. Ten single-lung transplant patients were included.
      Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2
      (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (
      0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular
      lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index
      was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water
      index was higher in the group of PaO2/FiO2 ratio <=150 mmHg compared with the
      group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary
      vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06).
      CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared
      with pulmonary artery catheter. However, it might be useful to assess pulmonary
      edema in acute respiratory failure after single-lung transplantation.

PMID- 29203300
TI  - Atypical Venous Valve of the Internal Jugular Vein.

PMID- 29203301
TI  - Ischemic Mitral Regurgitation: A Paradigm Shift in Surgical Management?

PMID- 29203302
TI  - Immunomodulatory effects of a rationally designed peptide mimetic of human
      IFNbeta in EAE model of multiple sclerosis.
AB  - The efficiency of interferon beta (IFNbeta)-based drugs is considerably limited
      due to their undesirable properties, especially high immunogenicity. In this
      study, for the first time we investigated the impact of a computationally
      designed peptide mimetic of IFNbeta, called MSPEP27, in the animal model of MS. A
      peptide library was constructed using the Rosetta program based on the
      predominant IFNAR1-binding site of IFNbeta. Molecular docking studies were
      carried out using ClusPro and HADDOCK tools. The GROMACS package was subsequently
      used for molecular dynamics (MD) simulations. Validation of peptide-receptor
      interaction was carried out using intrinsic fluorescence measurements. To explore
      in silico findings further, experimental autoimmune encephalomyelitis (EAE) was
      induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein
      (MOG35-55). Mice were then separated into distinct groups and intravenously
      received 10 or 20mgkg-1 of MSPEP27 or IFNbeta. The inflammatory mediators were
      monitored by immunohistochemistry (IL17, CD11b, CD45), quantitative real-time PCR
      (MMP2, MMP9, TIMP-1) and enzyme-linked immunosorbent assay (IL1beta, TNFalpha)
      methods. Among the library of tolerated peptides, MSPEP27, a peptide with
      favorable physicochemical properties, was chosen for further experiments. This
      peptide was shown to significantly interact with IFNAR1 in a dose-dependent
      manner. Like IFNbeta, MSPEP27 could efficiently bind to IFNAR1 and form a stable
      peptide-receptor complex during 30ns MD simulations. In vivo analyses revealed
      that MSPEP27 could lessen inflammation by modulating the levels of inflammatory
      mediators. According to our results, MSPEP27 peptide could efficiently bind to
      IFNAR1 and suppress neuroinflammation in vivo. We conclude that MSPEP27 has
      protective effects against MOG-induced EAE via reduction of immune dysfunction
      and inflammation.

PMID- 29203303
TI  - Interactive effects of morphine and nicotine on memory function depend on the
      central amygdala cannabinoid CB1 receptor function in rats.
AB  - The present study investigated the possible involvement of the central amygdala
      (CeA) cannabinoid receptors type-1 (CB1Rs) in the interactive effects of morphine
      and nicotine on memory formation in a passive avoidance learning task. Our
      results showed that systemic administration of morphine (3 and 6mg/kg, s.c.)
      immediately after training phase impaired memory consolidation and induced
      amnesia. Administration of nicotine (0.3 and 0.6mg/kg, s.c.) before testing phase
      significantly restored morphine-induced amnesia, suggesting a cross state
      dependent learning between morphine and nicotine. The results showed that while
      the administration of the lower dose of nicotine (0.1mg/kg, s.c.) per se did not
      induce a significant effect on morphine-induced amnesia, intra-CeA injection of
      arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor agonist (3 and
      4ng/rat), significantly potentiated the nicotine response. Furthermore, the
      blockade of the CeA cannabinoid CB1 receptors by the injection of AM251 (0.75 and
      1ng/rat) reversed the potentiative effect of nicotine (0.6mg/kg, s.c.) on
      morphine-induced amnesia. It should be considered that bilateral injection of the
      same doses of ACPA or AM251 (0.5-1ng/rat) into the CeA by itself had no effect on
      morphine response in a passive avoidance learning task. Confirmed by the cubic
      interpolation planes, the dose-response data revealed a cross-state-dependent
      learning between morphine and nicotine which may be mediated by the CeA
      endocannabinoid system via CB1 receptors.

PMID- 29203304
TI  - Post-chikungunya chronic inflammatory rheumatism: Follow-up of cases after 1 year
      of infection in Tolima, Colombia.
AB  - INTRODUCTION: Chronic Inflammatory Rheumatism (CIR) is one of the recognized and
      increasingly reported consequence post-chikungunya infection (pCHIK) in Colombia
      and Latin America. METHODS: Retrospective cohort study of 128 patients with CHIK
      that persisted with pCHIK-CIR after 59-68 weeks (1.13-1.31 years). This
      information was evaluated by means of a telephone survey and according to
      validated criteria (WHO 2015) previously (patients with >12 weeks post-CHIK with
      >=1 manifestations [continuous/recurrent]: chronic polyarthralgia [pCHIK-CPA],
      stiffness and/or joint edema). RESULTS: Of the total CHIK-infected subjects
      finally included (n = 65), 28 (43.1%) reported pCHIK-CPA; and 38 patients (58.5%)
      at least one persistent rheumatological symptoms over the last year (pCHIK-CIR);
      38.5% of them, morning stiffness, 18.5% joint edema, and 3.1% joint redness. No
      significant sex differences were found; 60% of patients with pCHIK-CPA aged> 40
      years (RR = 3.75; 95%CI 1.47-9.53). The 29.2% of patients required medical
      attention because of symptoms. CONCLUSIONS: Nearly half of patients with CHIK had
      at least one rheumatologic symptom persistent over a year, and the third of them,
      pCHIK-CPA. These results are comparable with previous estimates obtained in other
      cohorts in the country (Risaralda and Sucre) and are consistent with results from
      other studies in France and India.

PMID- 29203305
TI  - Infectious complications in paediatric patients treated with extracorporeal
      membrane oxygenation.
AB  - INTRODUCTION: The aim of this study was to analyse the incidence, treatment and
      evolution of infections in children treated with ECMO. METHODS: A retrospective
      study based on a prospective database was performed. Children under the age of 18
      years treated with ECMO from September 2006 to November 2015 were included. The
      patients' clinical characteristics were collected, together with ECMO technique,
      cultures and treatment of infection. RESULTS: One hundred patients with a median
      age of 11 months were analysed. Heart disease was diagnosed in 94 patients. An
      infection was suspected and antibiotic treatment was initiated in 51 patients,
      although only 22 of them were microbiologically confirmed. The most common
      infection was sepsis (49%), followed by pneumonia (35.3%) and urinary tract
      infection (9.8%). There were no differences in haematological parameters and
      acute phase reactants between children with infection and those without. Children
      who died had a higher incidence of infection during ECMO (60.4%) than the
      survivors (40.3%), but the difference did not reach statistical significance
      (P=.07). The duration of admission in the PICU was 57 days in patients with
      infection vs 37 days in patients without infection but the difference was not
      statistically significant (P=.067). CONCLUSIONS: Infection in children with ECMO
      is common. There are no specific infection parameters and less than half of the
      clinical infections are confirmed microbiologically. There was no statistically
      significant correlation between infection and mortality or duration of PICU stay.

PMID- 29203306
TI  - Reducing Variability of Radiation Dose in CT: The New Frontier in Patient Safety.
AB  - PURPOSE: Although reducing radiation dose in CT examinations is an important
      goal, also important in the management of radiation dose is ensuring consistency
      of dose administered for a given type of examination. We have implemented an
      approach to reducing variance in CT radiation dose by standardizing protocols and
      implementing software that decreases variance. METHODS: A multifaceted approach
      to reducing variance in CT radiation dose was utilized: (1) establishment of the
      Radiation Dose Optimization Committee, (2) standardization of protocols, and (3)
      implementation of scanner software. Two periods of data were collected: pre
      intervention (January 1, 2013, to July 31, 2014) and postintervention (January 1,
      2016, to December 31, 2016). The period from August 1, 2014, to December 31,
      2015, represented the time the major interventions were performed. RESULTS: The
      average radiation dose for all CT exams performed during the pre-intervention
      period (n = 39,314) was 22.3 CTDIvol with an SD of 17.0. The average radiation
      dose for all CT exams performed during the postintervention period (n = 49,863)
      was 13.6 CTDIvol with an SD of 9.01. The postintervention variance was
      significantly decreased (P < .0001). CONCLUSIONS: A significant decrease in the
      variability of our network CT radiation dose was achieved as a result of a
      combination of standardizing protocols across the network and implementation of
      advanced software that effectively managed radiation dose, all overseen by the
      Radiation Dose Optimization Committee.

PMID- 29203307
TI  - Development of a Severe Traumatic Brain Injury Consensus-Based Treatment Protocol
      Conference in Latin America.
AB  - BACKGROUND: Severe traumatic brain injury (sTBI) is a significant global health
      problem disproportionately affecting low- and middle-income countries (LMICs).
      Management of intracranial hypertension in sTBI is crucial to survival and
      optimal recovery. Practitioners in high-income countries routinely use
      intracranial pressure (ICP) monitors although their usefulness has been
      questioned. ICP monitors are usually unavailable in LMICs. No consensus
      based/tested protocols or literature exists for sTBI treatment without ICP
      monitoring. METHODS: Investigators developed serial SurveyMonkey surveys for
      Latin American neurointensivists and neurosurgeons to determine current practice.
      These clinicians had extensive routine ongoing experience in sTBI without ICP
      monitoring. Surveys were administered and analyzed before/during/after a 2015
      Buenos Aires consensus conference. Investigators identified areas of convergence
      blinded from colleagues' responses. A 47-clinician task force, representing 15
      countries, who routinely manage patients with sTBI without monitors developed
      consensus-based treatment guidelines during a 3-day facilitated conference.
      RESULTS: Elements were added to the protocol at an 80% agreement threshold.
      Follow-on surveys resolved remaining elements to 97% agreement. The protocol
      addresses both tapering (on improvement) and neuroworsening. Staged treatment
      options were identified, plus unique clinical practice issues. This process
      introduced a research method to a large multidisciplinary group of LMIC
      clinicians. This report describes the process used to develop an LMIC-specific
      protocol that is transferable to other diseases/injuries. The protocol is being
      tested in 5 LMICs. CONCLUSIONS: We derived consensus-based guidelines for sTBI
      treatment without ICP monitoring, and introduced a research method to a large
      multidisciplinary group of LMIC clinicians naive to such methods.

PMID- 29203308
TI  - Magnetic Resonance Imaging Undetectable Epiduroscopic Hotspot in Chronic
      Diskogenic Back Pain-Does Sinuvertebral Neuropathy Actually Exist?
AB  - BACKGROUND: The causes of chronic diskogenic back pain have not yet been clearly
      identified. Neural ingrowth around the annulus is widely considered to be one of
      the possible cause. However, neuropathy around the annulus has yet to be observed
      visually. We report a case of a hotspot that was observed in an epiduroscopic
      view, but not in imaging findings. CASE DESCRIPTION: A 46-year-old woman was
      admitted with pain in the back, left buttock, and posterior thigh for 2 years. A
      straight leg raising test was positive on the left side, and left great toe
      dorsiflexion was decreased to grade 3/5. The Visual Analog Scale pain score was
      7/10. On the basis of her symptoms, epidural block, medial branch block,
      sacroiliac joint block, piriformis muscle injection, physical therapy, and
      medication were attempted, but no improvement in symptoms was observed. A
      provocation test was performed at the L3-L4, L4-L5, and L5-S1 intervertebral
      disks, and severe pain was induced in the L5-S1 intervertebral disk, which was
      not suspicious on magnetic resonance imaging. We performed transforaminal
      epiduroscopic laser ablation on L5-S1 and found a hotspot on L5-S1 during the
      procedure. During laser provocation of the hotspot, the patient complained of
      severe pain in her lower back and legs, and her pain decreased after ablation of
      hotspot with laser and improvement in motor weakness was noticed. CONCLUSION: In
      this study, we observed annulus hotspots, which have not been observed in imaging
      studies such as computed tomography or magnetic resonance imaging in patients
      with chronic back pain and leg pain, and observed remarkable symptom improvement
      after transforaminal epiduroscopic laser ablation.

PMID- 29203309
TI  - Spontaneous Acute Arterial Subdural Hematoma.
AB  - BACKGROUND: Spontaneous acute arterial subdural hematoma (SDH) is a rare entity
      caused by hemorrhage from a cortical perisylvian artery without a known
      precipitant. CASE DESCRIPTION: A 53-year-old man presented with a 2-day history
      of acute-onset headache and dysphasia. He had a generalized seizure on arrival to
      hospital and no history of trauma. A computed tomography demonstrated an acute
      left-sided SDH. A computed tomography angiogram and a digital subtraction
      angiogram demonstrated active contrast extravasation into the SDH. A craniotomy
      was performed to evacuate the hematoma; the bleeding perisylvian artery was
      visualized and coagulated. CONCLUSIONS: We report a rare case of acute SDH and
      present a review of the literature. The etiology, investigation, and management
      of this rare neurosurgical emergency are discussed.

PMID- 29203310
TI  - Rosiglitazone Infusion Therapy Following Minimally Invasive Surgery for
      Intracranial Hemorrhage Evacuation Decreased Perihematomal Glutamate Content and
      Blood-Brain Barrier Permeability in Rabbits.
AB  - OBJECTIVE: To observe effects of rosiglitazone (RSG) infusion therapy on
      perihematomal peroxisome-proliferator-activated receptor gamma (PPARgamma),
      glutamate, blood-brain barrier (BBB) permeability, and brain edema. METHODS:
      Fifty male rabbits (2.8-3.4 kg) were randomly assigned to a normal control (NC)
      group, model control (MC) group, RSG group, minimally invasive surgery (MIS)
      group, or MIS and RSG (MIS+RSG) group. Intracranial hemorrhage was induced in all
      rabbits except for the NC group. MIS procedures were performed to evacuate the
      intracranial hemorrhage 6 hours after the intracranial hemorrhage model was
      prepared successfully. The animals were sacrificed on day 7, and the
      perihematomal brain tissue was obtained to determine PPARgamma, glutamate, and
      BBB permeability. RESULTS: Compared with the MC group, the MIS group displayed a
      remarkable decrease in PPARgamma, glutamate, and BBB permeability. The RSG group
      showed similar results in glutamate level and BBB permeability but a significant
      increase in PPARgamma. The MIS+RSG group displayed an increase in PPARgamma and a
      more significant decrease in glutamate, BBB permeability, and neurologicl deficit
      scores compared with the other groups. CONCLUSIONS: Performing MIS followed by
      RSG infusion therapy might increase PPARgamma expression and might be more
      efficacious for reducing glutamate level and BBB permeability and improving
      neurologic function than MIS or RSG therapy used alone.

PMID- 29203311
TI  - Lateral Ventricular Volume Asymmetry Predicts Poor Outcome After Spontaneous
      Intracerebral Hemorrhage.
AB  - BACKGROUND: Midline shift (MLS) has been a known predictor for prognosis after
      spontaneous intracerebral hemorrhage (ICH), whereas it is secondary to lateral
      ventricular compression. In this study, we investigated whether lateral
      ventricular volume (LVV) asymmetry caused by ventricular compression was
      independently associated with poor outcome of ICH. METHODS: We retrospectively
      studied clinical patients with spontaneous ICH from January 2010 to January 2017.
      LVV was calculated using slicer software. LVV ratio (LVR) was then determined to
      quantitatively evaluate LVV asymmetry, and its relationship with poor outcome was
      tested by logistic regression model. Receiver operating characteristic (ROC)
      curve analysis was performed to identify the optimized baseline LVR cutoff point
      to predict poor outcome. RESULTS: 188 patients were included, of whom 41%
      (77/188) experienced a poor outcome. Multivariate logistic regression analysis
      identified baseline LVR as an independent predictor for poor outcome after ICH.
      The predictive value of baseline LVR was confirmed by ROC analysis (area under
      the curve = 0.742; P < 0.001). The optimized baseline LVR cutoff point was 3.7,
      with a sensitivity of 64.9% and specificity of 80.2%. Using LVR >3.7 as an
      exposure factor yielded an odds ratio of 7.49 (P < 0.001), and a risk ratio of
      2.98 (P < 0.001). CONCLUSIONS: LVV asymmetry was associated with clinical
      prognosis after ICH, and high LVR (>3.7) might independently predict poor
      outcome.

PMID- 29203312
TI  - Microvascular Decompression for Treatment of Trigeminal Neuralgia: Factors That
      Predict Complete Pain Relief and Study of Efficacy and Safety in Older Patients.
AB  - OBJECTIVE: Microvascular decompression (MVD) is an effective method for directly
      treating the etiology of trigeminal neuralgia (TGN). This study aims to
      investigate the factors that predict complete pain relief after MVD for treatment
      of TGN, and to study efficacy and safety in older patients. METHODS: This study
      was conducted in patients with TGN that were treated by MVD at Siriraj Hospital
      between 2004 and 2015. Cases with secondary TGN were excluded. Data was gathered
      from medical records, preoperative magnetic resonance imaging, intraoperative
      findings, and by telephone in patients lost to follow-up. RESULTS: Of 110
      included patients, 68 and 42 patients were younger and older than 60 years,
      respectively. Median age was 53.6 years old. Typical type of TGN, paroxysmal
      pain, large offending vessel on preoperative magnetic resonance imaging, and
      multiple locations of trigeminal nerve compression were associated with early
      postoperative pain-free status. No variables were associated with long-term
      outcome. Multivariate analysis using binary logistic regression revealed typical
      type of TGN to be the only factor associated with early postoperative pain-free
      status. No significant difference was observed between the <60 and >=60 age
      groups for surgical outcome and rate of complications. CONCLUSIONS: Presence of
      typical type TGN was the only factor found to independently predict a pain-free
      outcome in the early postoperative period. No factors were associated long-term
      pain-free outcome. MVD is an effective and safe operative procedure, and it
      should be regarded as a safe and viable alternative for treating intractable TGN
      in older patients.

PMID- 29203313
TI  - Determining the Lower Limit of Cerebral Perfusion Pressure in Patients Undergoing
      Decompressive Craniectomy Following Traumatic Brain Injury.
AB  - BACKGROUND: In patients with severe traumatic brain injury (TBI), maintaining
      systolic blood pressure >90 mm Hg, intracranial pressure (ICP) <20 mm Hg and
      cerebral perfusion pressure (CPP) >60-70 mm Hg is recommended to improve clinical
      outcomes. A recommended CPP value for patients treated with decompressive
      craniectomy (DC) has not been clearly studied. We aimed to determine whether the
      targeted CPP can be lowered in patients treated with DC. METHODS: This
      retrospective analysis included 191 patients who underwent DC for TBI. All
      patients were monitored for ICP and blood pressure during and after DC. CPP was
      calculated every 2 hours after DC. Patient outcomes were evaluated 6 months after
      initial treatment. RESULTS: Mean patient age was 50.8 years (median 52 years),
      and 79.1% of patients were male. Initial Glasgow Coma Scale score was 6.2 (median
      6). Comparing clinical outcome based on postoperative ICP >25 mm Hg and <25 mm
      Hg, Extended Glasgow Outcome Scale score was 1.4 (>25 mm Hg) and 4.9 (<25 mm Hg)
      (P = 0.000). In patients maintained at ICP <25 mm Hg, mortality was increased
      significantly with CPP between 35 mmHg and 30 mm Hg (chi2, P = 0.029 vs. P =
      0.062). CONCLUSIONS: Patients with TBI who underwent DC with postoperative ICP
      maintained <25 mm Hg and CPP >35 mm Hg may have similar mortality as patients
      with CPP >60-70 mm Hg who did not undergo DC. For patients with TBI who undergo
      DC, targeted CPP might be lowered to 35 mm Hg if ICP is maintained <25 mm Hg.

PMID- 29203314
TI  - Endoscopic Transseptal Approach with Posterior Nasal Spine Removal: A Wide
      Surgical Corridor to the Craniovertebral Junction and Odontoid: Technical Note
      and Case Series.
AB  - BACKGROUND: The transnasal approach to lesions involving the craniovertebral
      junction represents a technical challenge because of limited inferior exposure.
      The endoscopic transseptal approach (EtsA) with posterior nasal spine (PNS)
      removal is described. This technique can create a wide exposure of the
      craniovertebral junction, thereby increasing the caudal exposure. METHODS: On
      patients undergoing anterior craniovertebral junction decompression, we
      calculated the degree of exposure on the sagittal plan through a paraseptal
      route, an EtsA without and with PNS removal. The horizontal exposure and working
      area with the latter approach were also evaluated. RESULTS: Five patients
      underwent the transnasal procedure. The age of patients ranged from 34-71 years.
      All patients harbored basilar impression. The mean postoperative Nurick grade (1,
      8) was improved versus the average preoperative grade (3). The average follow-up
      duration was 16 months. All patients underwent occipitocervical fixation. The
      mean vertical distances, from the clinoid recess to the inferior most limit with
      the paraseptal approach, EtsA without and with PNS removal were 38.52, 44.12, and
      51.16 mm, respectively. The difference between our approach and a standard
      paraseptal route was statistically significant (P = 0.041; P< 0.05). The mean
      horizontal distances were 31.68 mm (mononostril entry) and 35.37 mm (binostril
      entry). The mean working area was 1795.53 mm2. CONCLUSIONS: Endoscopic endonasal
      approaches to the craniovertebral junction are increasing, but the downward
      extension on the anterior cervical spine represents a limit. Therefore, many
      surgeons prefer transoral or transcervical approaches. The EtsA with PNS removal
      allows for a more caudal exposure than the standard paraseptal approach, with
      reduced nasal trauma.

PMID- 29203315
TI  - Long-Term Remission of Recurrent Brainstem Pilocytic Astrocytoma with Neuraxis
      Dissemination Using Recombinant Human Endostatin After Failure of Vincristine and
      Carboplatin.
AB  - BACKGROUND: There is no standard salvage treatment for recurrent and/or
      unresectable brainstem low-grade gliomas after failure from carboplatin and
      vincristine chemotherapy. Recombinant human endostatin (rh-ES), a mild inhibitor
      of angiogenesis, has been used for treating lung cancer. But so far as we know,
      there is no experience for brainstem gliomas. CASE DESCRIPTION: The authors
      present a pediatric case of recurrent brainstem pilocytic astrocytoma with
      neuraxis dissemination who experienced tumor progression with carboplatin and
      vincristine chemotherapy but then had a dramatic and long-term remission for at
      least 29 months after combined treatment of rh-ES with carboplatin and
      vincristine. CONCLUSION: This case suggests that the addition of rh-ES to
      carboplatin and vincristine regimens may be synergistic and results in a long
      term remission in patients with brainstem low-grade gliomas, even if the tumor is
      widely spread in the central nervous system.

PMID- 29203316
TI  - Cervical Rib Prevalence and its Association with Thoracic Outlet Syndrome: A Meta
      Analysis of 141 Studies with Surgical Considerations.
AB  - BACKGROUND: Cervical ribs (CR) are supernumerary ribs that arise from the seventh
      cervical vertebra. In the presence of CR, the boundaries of the interscalene
      triangle can be further constricted and result in neurovascular compression and
      thoracic outlet syndrome (TOS). The aim of our study was to provide a
      comprehensive evidence-based assessment of CR prevalence and their association
      with TOS as well as surgical approach to excision of CR and surgical patients'
      characteristics. METHODS: A thorough search of major electronic databases was
      conducted to identify any relevant studies. Data on the prevalence, laterality,
      and side of CR were extracted from the eligible studies for both healthy
      individuals and patients with TOS. Data on the type of TOS and surgical approach
      to excision of CR were extracted as well. RESULTS: A total of 141 studies (n =
      77,924 participants) were included into the meta-analysis. CR was significantly
      more prevalent in patients with TOS than in healthy individuals, with pooled
      prevalence estimates of 29.5% and 1.1%, respectively. More than half of the
      patients had unilateral CR in both the healthy and the TOS group. The analysis
      showed that 51.3% of the symptomatic patients with CR had vascular TOS, and 48.7%
      had neurogenic TOS. Most CR were surgically excised in women using a
      supraclavicular approach. CONCLUSIONS: CR ribs are frequent findings in patients
      with TOS. We recommended counseling asymptomatic patients with incidentally
      discovered CR on the symptoms of TOS, so that if symptoms develop, the patients
      can undergo prompt and appropriate workup and treatment.

PMID- 29203317
TI  - Long-Term Outcome of Repeat Microvascular Decompression for Hemifacial Spasm.
AB  - OBJECTIVE: Although repeat microvascular decompression (MVD) for hemifacial spasm
      (HFS) in patients with failed prior MVD is potentially curative, little is known
      about the long-term results of repeat MVD. We aimed to evaluate the long-term
      outcomes and complications after repeat MVD for HFS. METHODS: We performed repeat
      MVD on 78 consecutive patients who had undergone a prior MVD >1 year previously.
      Follow-up data were available for 58 patients, with a median follow-up period of
      8.6 years (range, 6.9-10.2 years). The patients were assessed for intraoperative
      findings, relief results, and complications at discharge and at follow-up, as
      well as the associations between the preoperative characteristics and outcomes.
      RESULTS: At discharge, of 78 patients with repeat MVD, 72 (92.3%) achieved
      complete spasm resolution and 1 (2.6%) had significantly improved spasm
      resolution. Of all patients, 9% (7 of 78) presented short-term complications,
      including partial hearing loss, hemifacial paresis, and cerebrospinal fluid leak.
      At follow-up, 45 of 58 (77.6%) patients had complete relief and 10 of 58 (17.2%)
      had improved relief. Permanent complications occurred in 14 patients (24.1%),
      with partial hearing loss and mild hemifacial paresis being the most common.
      Despite the complications, 51 of 58 patients (91.4%) reported an excellent life
      quality. No significant correlation was found between preoperative
      characteristics, such as age, interval to prior MVD, or interval to recurrence,
      and outcomes including short-term or long-term relief results and complications.
      CONCLUSIONS: Repeat MVD provides lasting relief for most patients with persistent
      or recurrent HFS, albeit with a relatively high complication rate.

PMID- 29203318
TI  - Lymph node ratio as a prognostic factor for survival in patients with head and
      neck squamous cell carcinoma.
AB  - OBJECTIVE: The purpose of this study is to validate the concept of lymph node
      ratio (LNR) in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of
      63 patients with HNSCC who underwent resection of the primary tumor combined with
      neck dissection in our institution were analyzed in this study. LNR was defined
      as the number of positive lymph nodes divided by the total number of lymph nodes
      excised. LNR was categorized into two groups (<0.068 and >=0.068) according to
      the results of receiver-operating characteristic plots for determination of the
      cut-off value. RESULTS: LNR>=0.068 was associated with poor overall survival
      (OS), progression-free survival (PFS) and locoregional recurrence-free survival
      (LRFS) after resection of the primary tumor combined with neck dissection in
      patients with HNSCC. Univariate and multivariate data analysis showed that
      LNR>=0.068 was an independent prognostic factor for OS, PFS and LRFS. Both
      pathological T stage status (pT3 or 4) and >=3 positive LNs were also an
      independent prognostic factors for PFS in patients with HNSCC in our univariate
      and multivariate analysis. CONCLUSION: These results suggested that LNR could be
      useful tools in identifying HNSCC patients with poor outcomes.

PMID- 29203319
TI  - Critical power: How different protocols and models affect its determination.
AB  - : In cycling, critical power (CP) and work above CP (W') can be estimated through
      linear and nonlinear models. Despite the concept of CP representing the upper
      boundary of sustainable exercise, overestimations may be made as the models
      possess inherent limitations and the protocol design is not always appropriate.
      OBJECTIVES: To measure and compare CP and W' through the exponential (CPexp), 3
      parameter hyperbolic (CP3-hyp), 2-parameter hyperbolic (CP2-hyp), linear
      (CPlinear), and linear 1/time (CP1/time) models, using different combinations of
      TTE trials of different durations (approximately 1-20min). DESIGN: Repeated
      measures. METHODS: Thirteen healthy young cyclists (26+/-3years; 69.0+/-9.2kg;
      174+/-10cm; 60.4+/-5.9mLkg-1min-1) performed five TTE trials on separate days. CP
      and W' were modeled using two, three, four, and/or five trials. All models were
      compared against a criterion method (CP3-hyp with five trials; confirmed using
      the leaving-one-out cross-validation analysis) using smallest worthwhile change
      (SWC) and concordance correlation coefficient (CCC) analyses. RESULTS: CP was
      considerably overestimated when only trials lasting less than 10min were
      included, independent of the mathematical model used. Following CCC analysis, a
      number of alternative methods were able to predict our criterion method with
      almost a perfect agreement. However, the application of other common approaches
      resulted in an overestimation of CP and underestimation of W', typically these
      methods only included TTE trials lasting less than 12min. CONCLUSIONS:
      Estimations from CP3-hyp were found to be the most accurate, independently of TTE
      range. Models that include two trials between 12 and 20min provide good agreement
      with the criterion method (for both CP and W').

PMID- 29203321
TI  - Lipopolysaccharide impairs mucin secretion and stimulated mucosal immune stress
      response in respiratory tract of neonatal chicks.
AB  - The chicken immune system is immature at the time of hatching. The development of
      the respiratory immune system after hatching is vital to young chicks. The aim of
      this study was to investigate the effect of LPS on respiratory mucin and IgA
      production in chicks. In this study, we selected 7days old AA broilers of similar
      weigh randomly; LPS atomized at 1mg/kg body weigh dose in the confined space of 1
      cubic meter. The chickens exposed for 2h. Then collect samples after 4h and 8h
      respectively. Compared to control, LPS inhibited mucus production in BALF, caused
      a rising trend of the concentration of IgA in serum and BALF, and increased the
      protein expression of IgA in lung tissue. And LPS treat induced a decreasing
      trend of the mRNA expression of IL-6 and TGF-beta and significantly decreased the
      gene expression of TGF-alpha and EGFR after 4h. After 8h the LPS suppressed the
      TGF-beta mRNA expression significantly. In addition, LPS treatment stimulated
      airway epithelial cilia sparse after 4h. Therefore, results proved: LPS can
      impair mucin expression and stimulated mucosal immune stress reaction of
      respiratory tract. This study suggested that LPS involved in respiratory tract
      mucosal immune response in chicks by regulating gene expression of cytokines and
      epithelial growth factors.

PMID- 29203322
TI  - Effects of in ovo exposure to benzo[k]fluoranthene (BkF) on CYP1A expression and
      promoter methylation in developing chicken embryos.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are toxic environmental pollutants that
      are potent teratogens. Recent research suggests that early life exposure to PAHs
      can affect health outcomes later in life. Some of these latent responses may be
      mediated by epigenetic mechanisms such as DNA methylation. The role of DNA
      methylation in regulating responses to PAHs in birds is currently unknown. Here,
      we assess the effect of in ovo exposure to the model PAH, benzo[k]fluoranthene
      (BkF), on aryl hydrocarbon receptor (AHR) mediated cytochrome P4501A (CYP1A) gene
      expression and promoter methylation in chicken embryos. Fertilized chicken eggs
      were injected with BkF (0-100MUg/kg) prior to incubation. BkF exposure was
      associated with an increase in CYP1A4 and CYP1A5 mRNA levels at mid-incubation
      (embryonic day 10), which dropped to baseline levels towards the end of the
      incubation period (embryonic day 19). The transient induction in CYP1A expression
      was accompanied by small but significant increases in CYP1A promoter methylation,
      which persisted until after shortly after hatching. Methylation within the CYP1A
      promoter was correlated with levels of CYP1A5, but not CYP1A4 mRNA.
      Characterization of the role of DNA methylation in the AHR response pathway may
      increase our understanding of the effects of early life exposure to PAHs in
      birds.

PMID- 29203323
TI  - [Association between type 2 diabetes and physical activity in individuals with
      family history of diabetes].
AB  - OBJECTIVE: To investigate whether the association between type 2 diabetes (T2D)
      and family history of diabetes is modified by the levels of physical activity in
      the Chilean population. METHOD: In this study were included 5129 participants
      from the cross-sectional 2009-2010 National Health Survey. Physical activity
      level was assessed using the Global Physical Activity Questionnaire and family
      history of T2D, through self-reporting. The association between diabetes, family
      history of diabetes and physical activity was determined using logistic
      regression. RESULTS: The odds of developing T2D in people with family history of
      this pathology is high, independent of their levels of physical activity and
      adiposity. Both men and women with family history of T2D have a higher
      probability of developing T2D. The odds ratio for having T2D was 5,49 (95%CI:
      3,85-7,84; p <0,0001) in women, and 8,16 (95%CI: 4,96-13,4; p <0,0001) in men
      with family history of T2D and low levels of physical activity in comparison to
      those with high levels of physical activity and without a family history.
      CONCLUSION: Given the elevated risk of developing T2D presented by individuals
      with a family history of this pathology, and the effect of physical activity in
      reducing such risk, people with family history of diabetes may need higher levels
      of physical activity to attenuate their susceptibility to T2D.

PMID- 29203320
TI  - Characterization of basal gene expression trends over a diurnal cycle in
      Xiphophorus maculatus skin, brain and liver.
AB  - Evolutionarily conserved diurnal circadian mechanisms maintain oscillating
      patterns of gene expression based on the day-night cycle. Xiphophorus fish have
      been used to evaluate transcriptional responses after exposure to various light
      sources and it was determined that each source incites distinct genetic responses
      in skin tissue. However, basal expression levels of genes that show oscillating
      expression patterns in day-night cycle, may affect the outcomes of such
      experiments, since basal gene expression levels at each point in the circadian
      path may influence the profile of identified light responsive genes. Lack of
      knowledge regarding diurnal fluctuations in basal gene expression patterns may
      confound the understanding of genetic responses to external stimuli (e.g., light)
      since the dynamic nature of gene expression implies animals subjected to stimuli
      at different times may be at very different stages within the continuum of
      genetic homeostasis. We assessed basal gene expression changes over a 24-hour
      period in 200 select Xiphophorus gene targets known to transcriptionally respond
      to various types of light exposure. We identified 22 genes in skin, 36 genes in
      brain and 28 genes in liver that exhibit basal oscillation of expression
      patterns. These genes, including known circadian regulators, produced the
      expected expression patterns over a 24-hour cycle when compared to circadian
      regulatory genes identified in other species, especially human and other
      vertebrate animal models. Our results suggest the regulatory network governing
      diurnal oscillating gene expression is similar between Xiphophorus and other
      vertebrates for the three Xiphophorus organs tested. In addition, we were able to
      categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit
      circadian based oscillating expression patterns.

PMID- 29203324
TI  - [Towards a social determinants-oriented approach to public health: workshop
      report].
AB  - This article is the result of a workshop with public health experts held in
      Granada (Spain) in October 2015 in order to reflect upon the components of the
      framework that should be part of a public health approach based on the social
      determinants of health. Advocacy and training professionals in health advocacy
      were identified as key elements where this was needed. During the workshop, it
      was agreed that the gender perspective, the salutogenic approach,
      interdisciplinary work and particular attention to disadvantaged groups are
      crucial. The importance of working from a human rights' framework and promoting
      legislative changes were also mentioned. Moreover, the group mentioned that even
      though much progress has been made identifying social determinants of health and
      creating conceptual frameworks, there is limited knowledge about how to intervene
      to reduce health inequality gaps in our societies.

PMID- 29203325
TI  - [Multiple sclerosis, loss of functionality and gender].
AB  - OBJECTIVE: To identify the type of support and assistance that patients with
      multiple sclerosis need in order to cope with the loss of functionality, and to
      show how gender affects the perception of these needs. METHOD: Interpretative
      phenomenological qualitative study. LOCATION: Granada (Spain). Year: 2014.
      Intentional sample: 30 patients and 20 family caregivers. Data were gathered from
      26 interviews and 4 focus groups. The data were coded and analysed with the NVivo
      programme. RESULTS: The multiple sclerosis patients and family caregivers had
      different perceptions of the loss of capacity to undertake activities of daily
      living. Being able to self care was considered the last vestige of autonomy. The
      women with multiple sclerosis tried to take on the responsibility of housework,
      but the male caregivers became gradually involved in these tasks. Gender roles
      were redefined with respect to housekeeping. The multiple sclerosis patients
      showed a need for emotional support. Some of the men had abandoned the stereotype
      of the strong male as a result of the decline in their health. Adaptations in the
      home took place without planning them in advance. The use of mobility devices
      started on an occasional basis. A fear of stigma was an obstacle for regular use
      of assistive technology. CONCLUSIONS: Health care for people with multiple
      sclerosis should include family caregivers. Gender influences the perception that
      caregivers and patients have of the assistance they require to maximise their
      quality of life. This flags up several intervention areas for the follow-up and
      long-term care of these patients by the healthcare system.

PMID- 29203326
TI  - Crosstalk between reactive oxygen species and nitric oxide in plants: Key role of
      S-nitrosoglutathione reductase.
AB  - Nitric oxide (.NO) acts as signaling molecule in plants being involved in diverse
      physiological processes such as germination, root growth, stomata closing and
      response to biotic and abiotic stress. S-Nitrosoglutathione (GSNO) is the storage
      and transport form of.NO and has a very important function in.NO signaling since
      it can transfer its.NO moiety to other proteins (trans-nitrosylation). The level
      of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO
      reductase (GSNOR). In this way, this enzyme regulates the S-nitrosothiol levels
      and plays a balancing role in fine-tuning.NO signaling. Interestingly, oxidative
      post-translationally modification of GSNOR inhibited the activity of this enzyme
      suggesting a direct crosstalk between ROS- and RNS-signaling. In this review
      article the regulatory effects of ROS on GSNOR are highlighted and their
      physiological function in context of crosstalk between ROS and.NO and species in
      plants are discussed.

PMID- 29203327
TI  - ROS-induced ROS release in plant and animal cells.
AB  - Reactive oxygen species (ROS) play a key signaling role in plant and animal
      cells. Among the many cellular mechanisms used to generate and transduce ROS
      signals, ROS-induced ROS release (RIRR) is emerging as an important pathway
      involved in different human pathologies and plant responses to environmental
      stress. RIRR is a process in which one cellular compartment or organelle
      generates or releases ROS, triggering the enhanced production or release of ROS
      by another compartment or organelle. It was initially described in animal cells
      and proposed to mediate mitochondria-to-mitochondria communication, but later
      expanded to include communication between mitochondria and plasma membrane
      localized NADPH oxidases. In plants a process of RIRR was demonstrated to mediate
      long distance rapid systemic signaling in response to biotic and abiotic stress.
      This process is thought to involve the enhanced production of ROS by one cell
      that triggers the enhanced production of ROS by a neighboring cell in a process
      that propagates the enhanced "ROS production state" all the way from one part of
      the plant to another. In contrast to the intracellular nature of the RIRR process
      of animal cells, the plant RIRR process is therefore primarily studied at the
      cell-to-cell communication level. Studies on intracellular (organelle-to
      organelle, or organelle-to-NADPH oxidase) RIRR pathways are very scarce in
      plants, whereas studies on cell-to-cell RIRR are very scarce in animals. Here we
      will attempt to highlight what is known in both systems and what each system can
      learn from the other.

PMID- 29203328
TI  - Response to comment on "Indoor terrestrial gamma dose rate mapping in France: A
      case study using two different geostatistical models" by Warnery et al.
AB  - Elements to answer the points raised in the Letter in question are proposed,
      notably about exposure metrics and their influence on the results and statistical
      power of epidemiological studies.

PMID- 29203329
TI  - Bruch's membrane opening on optical coherence tomography in pediatric papilledema
      and pseudopapilledema.
AB  - PURPOSE: To determine whether the diameter of Bruch's membrane opening (BMO) can
      distinguish mild papilledema from pseudopapilledema using optical coherence
      tomography (OCT). METHODS: The medical records of pediatric patients with
      pseudopapilledma due to optic nerve head (ONH) drusen, patients with papilledema,
      and normal control subjects were retrospectively reviewed. All eyes underwent OCT
      imaging of the BMO and retinal nerve fiber layer (RNFL). Transverse horizontal
      diameter of the BMO and papillary height were measured. Mean BMO, papillary
      height, and RNFL were compared and receiver operating characteristic (ROC) curves
      were used to calculate the area under the curve (AUC) and determine BMO and RNFL
      cut-offs for papilledema and pseudopapilledema. RESULTS: A total of 90 eyes of 90
      subjects were included: 58 with pseudopapilledema, 19 with papilledema, and 13
      controls. In eyes with papilledema, mean BMO, papillary height, and RNFL
      decreased as papilledema resolved (1893.8 vs 1582.2 [P = 0.0003], 193.0 vs 108.9
      [P < 0.0001], 893.3 vs 695.5 [P = 0.0007], resp.). Eyes with mild papilledema had
      greater mean BMO and RNFL than those with pseudopapilledema and controls (1893.8
      vs 1541.9 vs 1628.8 [P < 0.0001, P = 0.0265] and 193.0 vs 108.7 vs 104.1 [P <
      0.0001, P < 0.0001], resp.). Papillary height in mild papilledema was similar to
      pseudopapilledema but greater than controls (893.3 vs 863.2 vs 593.5 [P = 0.47
      and P = 0.0001], resp.). ROC showed good diagnostic discrimination for BMO (AUC =
      0.81; 95% CI, 0.70-0.92) and RNFL (AUC = 0.96; 95% CI, 0.93-1.0) in
      distinguishing mild papilledema from pseudopapilledema. CONCLUSIONS: The
      horizontal transverse diameter of BMO is enlarged in eyes with mild papilledema
      and narrows as papilledema resolves. BMO and RNFL can be used together to help
      distinguish mild papilledema from pseudopapilledema in children.

PMID- 29203330
TI  - Changes in Caenorhabditis elegans gene expression following exposure to
      Photorhabdus luminescens strain TT01.
AB  - Photorhabdus bacteria enter into a mutualistic symbiosis with Heterorhabditis
      nematodes to infect insect larvae. However, they rapidly kill the model nematode
      Caenorhabditis elegans. One hypothesis for these divergent outcomes is that the
      nematode defense responses differ. To begin testing this hypothesis, we have
      systematically analyzed available data on the transcriptional response of C.
      elegans to P. luminescens strain Hb. From a starting pool of over 7000
      differentially expressed genes, we carefully chose 21 Heterorhabditis-conserved
      genes to develop as comparative markers. Using newly designed and validated qRT
      PCR primers, we measured expression of these genes in C. elegans exposed to the
      sequenced TT01 strain of P. luminescens, on two different media types. Almost all
      (18/21) of the genes showed a significant response to P. luminescens strain TT01.
      One response is dependent on media type, and a subset of genes may respond
      differentially to distinct strains. Overall, we have established useful resources
      and generated new hypotheses regarding how C. elegans responds to P. luminescens
      infection.

PMID- 29203331
TI  - A crucial role of paralogous beta-defensin genes in the Chinese alligator innate
      immune system revealed by the first determination of a Crocodilia defensin
      cluster.
AB  - The beta-defensin, one of the antimicrobial peptides (AMPs), is a significant
      component of the innate immune with a broad range of antimicrobial activities.
      Differing from the widely-studied mammals and birds, limited information about
      beta-defensins has been reported in reptiles, especially in crocodilians. As a
      same ancient species as dinosaurs and the most endangered species of 23
      crocodilians, the survival of Chinese alligator (Alligator sinensis) means a
      powerful immune system and possible involvement of AMPs in its immune resistance.
      In this study, we identified 20 novel Alligator sinensisbeta-defensin genes
      (AsBDs) from a 390 kb region using bioinformatic and experimental approaches, and
      successfully distinguished six orthologous AsBDs to birds and nine paralogous
      AsBDs undergoing gene duplication events. The amino acid alignment shows that the
      AsBD paralogs, like alpha-defensins, encode a significantly longer pro-piece
      comparing with the orthologs. The calculation of non-synonymous (dN) and
      synonymous (dS) substitutions in the mature peptide reveals that the AsBD
      paralogs experience a significantly higher selective pressure (dN/dS) than the
      orthologs, but a similar evolutionary force to alpha-defensins. The gene
      expression result indicates that the AsBD paralogs have a significantly higher
      expression level than the orthologos in gastrointestinal tract where the host is
      vulnerable to enteric pathogenic bacteria, as observed in alpha-defensins. These
      three pieces of evidence demonstrate that the AsBD paralogs do play an important
      role in maintaining long-term survival of this endangered reptile. Thus, this
      survey of AsBDs on the genomic structure, evolutionary characteristics, and
      expression pattern provides a genetic and immunological foundation for further
      investigating their antimicrobial function and alternative antibiotics
      potentiality.

PMID- 29203332
TI  - Toll-like receptor (TLR) 22, a non-mammalian TLR in Asian seabass, Lates
      calcarifer: Characterisation, ontogeny and inductive expression upon exposure
      with bacteria and ligands.
AB  - Toll-like receptor (TLR) 22 is a non-mammalian TLR found mostly in teleosts and
      characterized initially as a cell surface surveillance receptor for detecting
      extracellular long dsRNA. In the current study, the full-length cDNA sequence
      consisting of 3312 nucleotides encoding for 960 amino acids in Asian seabass
      (Lates calcarifer) TLR22 (AsTLR22) was identified. From the putative protein
      sequence, signature TLR domains such as 18 LRR domains, two transmembrane
      domains, a single LRR_CT domain and an intracellular TIR domain could be
      predicted. Phylogenetic analysis showed that AsTLR22 is clustered with other
      teleost TLR22 and is distinctly different from the other TLR groups. The
      transcript of AsTLR22 was ubiquitously expressed in all the tissues tested of
      healthy juveniles with the highest expression in gill followed by hindgut, spleen
      and skin. The AsTLR22 mRNA transcript was also detected in all the developmental
      stages as early as unfertilized eggs with higher expression in later stages such
      as neurula and early embryo. The dsRNA viral analogue, poly (I:C) and Gram
      negative bacterium, Vibrio alginolyticus, were found to modulate the AsTLR22
      expression in different tissues with the highest expression in kidney and liver.
      Gram-positive bacterium, Staphylococcus aureus, was also found to regulate the
      AsTLR22 expression at certain time-points with the highest expression in gill.
      Similarly, noticeable change in AsTLR22 expression was detected in SISK cell line
      induced with different ligands such as poly (I:C), LPS and PGN. The findings
      indicate that AsTLR22 responds in transcript level towards bacteria-borne PAMPs
      and extracellular dsRNA in the euryhaline teleost Asian seabass. Further, this
      might act as an important pathogen surveillance receptor during early
      developmental stages.

PMID- 29203333
TI  - Perinatal fluoxetine increases hippocampal neurogenesis and reverses the lasting
      effects of pre-gestational stress on serum corticosterone, but not on maternal
      behavior, in the rat dam.
AB  - There is increasing evidence that mental health concerns, stress-related mental
      illnesses, and parental stress prior to conception have long-term effects on
      offspring outcomes. However, more work is needed to understand how pre
      gestational stress might affect neurobehavioral outcomes in the mother. We
      investigated how chronic stress prior to gestation affects maternal behavior and
      related physiology, and aimed to determine the role that perinatal SSRIs have in
      altering these stress effects. To do this, female Sprague-Dawley rats were
      subject to chronic unpredictable stress (CUS) prior to breeding. During the
      perinatal period they were administered fluoxetine (10mg/kg/day). Four groups of
      dams were studied: Control+Vehicle, Pre-gestational Stress+Vehicle,
      Control+Fluoxetine and Pre-gestational Stress+Fluoxetine. Maternal weight,
      breeding success, and maternal caregiving behaviors were recorded. Measures of
      serum corticosterone and corticosteroid-binging globulin (CBG) and the number of
      immature neurons in the dorsal hippocampus were also assessed in the late
      postpartum. Main findings show pre-gestational stress resulted in poor
      reproductive success and maintenance of pregnancy. Pre-gestationally stressed
      dams also showed higher levels of nursing and fewer bouts of licking/grooming
      offspring in the first week postpartum - behaviors that were not reversed by
      perinatal fluoxetine treatment. In the dam, perinatal fluoxetine treatment
      reversed the effect of pre-gestational maternal stress on serum corticosterone
      levels and increased serum CBG levels as well as neurogenesis in the dorsal
      hippocampus. Maternal corticosterone levels significantly correlated with blanket
      and passive nursing. This work provides evidence for a long-term impact of stress
      prior to gestation in the mother, and shows that perinatal SSRI medications can
      prevent some of these effects.

PMID- 29203334
TI  - Sex differences in olfactory-induced neural activation of the amygdala.
AB  - Olfactory signals, including the scent of urine, are thought to be processed by
      specific brain regions, such as the medial amygdala (Me), and regulate sexual
      behavior in a sex-dependent manner. We aimed to reveal the sex-specific neural
      circuit from the accessory olfactory bulb (AOB) to Me by using a transgenic
      mouse. We quantified the long-lasting green fluorescent protein (GFP) expression
      profile, which was controlled by the c-fos promotor in a sex-dependent manner by
      the scent of urine. Female urine predominantly activated neurons of the
      posterodorsal medial amygdala (MePD) in male mice and the posteroventral medial
      amygdala (MePV) in female mice. Male urine, in contrast, generated the opposite
      pattern of activation in the Me. Secondary, the selective artificial activation
      of these circuits was used to examine their specific behavioral function, by
      using a dual Cre-loxP viral infection. AAV-hSyn-FLEX-hM3Dq-EGFP-the designer
      receptor exclusively activated by a designer drug-was infused into the AOB after
      infection with trans-synaptic AAV(DJ)-CMV-mCherry-2A-Cre-TTC into either the MePD
      or the MePV. Double virus-transfected mice were injected with hM3Dq activator and
      their sexual behavior was monitored. However, selective activation of sex
      dependent circuits, i.e., the AOB-MePD or AOB-MePV, did not significantly alter
      mounting or attack behavior in male mice. There were clear sex differences in the
      pheromone conveying circuits in the AOB-Me of mice. The sex-dependent functional
      activation of the Me, however, no effect on behavior. This suggests that a
      diverse number of nuclei and brain areas are likely to function in concert to
      successfully facilitate sexual and aggressive behaviors.

PMID- 29203335
TI  - Hex Maze: A new virtual maze able to track acquisition and usage of three
      navigation strategies.
AB  - Spatial navigation is a complex and multi-faceted skill that, in humans, is
      understood to encompass two distinct navigational strategies, namely allocentric
      and egocentric navigation. These differ in the frame of reference used and the
      brain networks activated. However, egocentric navigation can be further divided
      into two, equally distinct strategies depending on whether the navigator is using
      subject-to-object relations (egocentric-cue) or direction of body turns
      (egocentric-response) to navigate. To date, there are no experimental paradigms
      able to distinguish between participants' employment of allocentric, egocentric
      cue and egocentric-response strategies, and to track their usage over time. The
      current study presents the Hex Maze: a novel virtual environment that can not
      only distinguish between the three navigational strategies, but can also be used
      to index aspects of strategy use such as preference, acquisition, stability and
      competence. To illustrate this, 32 male and 32 female participants were presented
      with the Hex Maze and sex differences in strategy usage were explored. While the
      results offer some support for previously identified sex differences in strategy
      preference, there were no significant sex differences in the novel measures of
      strategy acquisition, stability, or multi-strategy competence. Additionally, our
      results suggest that strategy preference does not preclude learning to
      competently navigate using other strategies. Importantly, the current study
      offers validation for the Hex Maze as an unbiased method of exploring spatial
      navigation, and it is anticipated that this easy-to-use tool will be valuable
      across research and clinical settings.

PMID- 29203337
TI  - Shati/Nat8l knockout mice show behavioral deficits ameliorated by atomoxetine and
      methylphenidate.
AB  - We previously identified a novel molecule, SHATI/NAT8L, as having an inhibitory
      effect on methamphetamine dependence. We generated Shati/Nat8l knockout (KO) mice
      and found that they showed neurochemical changes and behavioral abnormalities
      related to attention deficit/hyperactivity disorder (AD/HD). In this study, we
      assessed validities of the Shati/Nat8l KO mice as a new animal model for AD/HD
      through a behavioral pharmacology approach. We conducted a locomotor activity
      test in a novel environment, a cliff avoidance test, and an object-based
      attention assay using Shati/Nat8l KO mice at the ages of 4 and 8 weeks. We found
      that at the ages of both 4 and 8 weeks, Shati/Nat8l KO mice showed hyperactivity
      in locomotor activity test, shortened jumping latency in cliff avoidance test,
      and lower recognition index in object-based recognition test. Moreover, we
      evaluated the effects of atomoxetine (ATX) and methylphenidate (MPH) on the
      behavioral deficits in Shati/Nat8l KO mice. As the result, almost all behavioral
      deficits were improved by the treatment of both ATX and MPH. Our findings suggest
      that Shati/Nat8l KO mice have an impaired neural system similar to AD/HD
      pathophysiology. Shati/Nat8l KO mice might serve as a novel and a useful animal
      model for the pathophysiology of AD/HD.

PMID- 29203336
TI  - Spontaneous recovery of traumatic brain injury-induced functional deficits is not
      hindered by daily administration of lorazepam.
AB  - Agitation and aggression are common sequelae of traumatic brain injury (TBI) and
      pose a challenge to physicians and other health providers during acute patient
      care and subsequent neurorehabilitation. Antipsychotic drugs (APDs) are routinely
      administered to manage TBI patients displaying such maladaptive behaviors despite
      several clinical and preclinical studies demonstrating that they hinder recovery.
      A potentially viable alternative to APDs may be the benzodiazepines, which have
      differing mechanisms of action. Hence, the aim of the study was to test the
      hypothesis that lorazepam (LOR) would not impede recovery after TBI. Anesthetized
      adult male rats received a cortical impact or sham injury and then were
      intraperitoneally administered LOR (0.1mg/kg, 1.0mg/kg, or 2.0mg/kg) or vehicle
      (VEH; 1mL/kg) commencing 24-h after surgery and once daily for 19days. Motor and
      cognitive outcomes were assessed on post-operative days 1-5 and 14-19,
      respectively. No differences were revealed among the four sham control groups and
      thus they were pooled into one inclusive SHAM group. The SHAMs performed better
      than all TBI groups on all assessments (p<0.05). Regarding TBI, the 2.0mg/kg LOR
      group performed better than the VEH and 0.1mg/kg or 1.0mg/kg LOR groups on every
      task (p<0.05); no differences were observed among the latter three groups on any
      endpoint (p>0.05). Overall, these preclinical behavioral data support the
      hypothesis and reveal a therapeutic benefit with the higher dose of LOR. The
      findings suggest that LOR may be an alternative, to APDs, for controlling
      agitation without compromising spontaneous recovery and perhaps could afford a
      dual benefit by also promoting therapeutic efficacy.

PMID- 29203338
TI  - The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation.
AB  - The Rvb1-Rvb2-Tah1-Pih1/prefoldin-like (R2TP/PFDL) complex is a unique chaperone
      that provides a platform for the assembly and maturation of many key multiprotein
      complexes in mammalian cells. Here, we propose to rename R2TP/PFDL as PAQosome
      (particle for arrangement of quaternary structure) to more accurately represent
      its unique function.

PMID- 29203339
TI  - Head and neck Merkel cell carcinoma: a retrospective case series and critical
      literature review with emphasis on treatment and prognosis.
AB  - OBJECTIVE: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high
      recurrence and mortality rates. More than half of MCCs occur in the head and neck
      region. This paper aims to present a retrospective case series study of primary
      MCCs of the head and neck treated in our department over 12 years. STUDY DESIGN:
      Six patients were identified, and their characteristics, treatment modalities,
      and outcomes are reported. A critical review of the current literature is also
      included to provide up-to-date information on MCCs with special emphasis on
      treatment modalities and disease prognosis. RESULTS: Management of head and neck
      MCCs requires early and accurate diagnosis and includes surgery, radiotherapy,
      and/or combination chemotherapy. Accurate cervical nodal staging is of paramount
      importance before establishing the definite treatment plan. CONCLUSIONS: The
      results of both our case series and literature data review indicate that elective
      management of regional lymph nodes is recommended instead of an observation
      approach for patients with no identifiable disease in the lymph nodes (cN0).
      Because the majority of MCCs arise in the head and neck region, oral and
      maxillofacial surgeons are likely be the first professionals who will encounter
      this disease and should therefore be aware of the current diagnostic and
      treatment modalities.

PMID- 29203340
TI  - Decidual ACVR2A regulates extravillous trophoblast functions of adhesion,
      proliferation, migration and invasion in vitro.
AB  - Decidual stromal cells form the largest proportion of maternal cells at the
      maternal-fetal interface. Our aim was to investigate the role of the pre
      eclampsia associated decidual activin receptor, ACVR2A, in regulating trophoblast
      functions at this interface. St-T1b and HTR-8/SVneo cell lines were used to model
      decidual stromal and trophoblast cells respectively. St-T1b conditioned medium
      inhibited HTR-8/SVneo adhesion, proliferation, migration and invasion; all
      effects that were attenuated by decidual ACVR2A siRNA transfection. These
      findings suggest that altered decidual ACVR2A expression perturbs the maternal
      fetal crosstalk involved in regulating trophoblast function at the interface,
      which may affect placentation and lead to pre-eclampsia.

PMID- 29203342
TI  - Effect of early second-look hysteroscopy on reproductive outcomes after
      hysteroscopic adhesiolysis in patients with intrauterine adhesion, a
      retrospective study in China.
AB  - OBJECTIVE: The aim of this study was to assess the effect of early second-look
      hysteroscopy after hysteroscopic adhesiolysis for intrauterine adhesions (IUAs)
      on the pregnancy rate (PR) and live birth rate (LBR). STUDY DESIGN: It is a
      retrospective, observational study of 151 women were referred to our institution
      from January 2010 to January 2016. Operative hysteroscopy for treatment of IUAs
      and office hysteroscopic follow-up to assess IUAs. We investigated demographic
      characteristics, menstrual pattern, previous intrauterine surgery, reproductive
      history, ovarian preservation assessment, tubal patency examination, husband's
      semen test, obstetric parameters, and surgical variables to evaluate the effect
      of early second-look hysteroscopy after hysteroscopic adhesiolysis on the PR and
      LBR. RESULTS: Of 151 women treated for IUAs, the general PR was 71.5% and LBR was
      53.0%. The PR and LBR were higher in the earlier second-look group (compared with
      second hysteroscopy later than 2 months group) and the group which received less
      than three times adhesiolysis (p < 0.05). The PR was higher in the amenorrhea
      group (compared with normal menses group) and recurrent miscarriage group
      (compared with infertility group) (p < 0.05). Logistic regression showed that the
      second-look time interval, times of operation to relieve adhesion, and pregnancy
      history were associated with the PR, while age and the second-look time interval
      were associated with the LBR. CONCLUSIONS: Early second-look hysteroscopic
      examinations within 2 months may increase the cumulative PR and LBR.

PMID- 29203343
TI  - Wide variation in organisation and clinical practice of paediatric intestinal
      failure teams: an international survey.
AB  - BACKGROUND & AIMS: We aimed to assess the current organisation and clinical
      practice of teams treating children with intestinal failure (IF) across Europe
      and compare the results with the current guideline. METHODS: A two-part online
      survey was sent to all the major European specialist IF services. The first part
      concerned general information about the team and patients monitored. The second
      part concerned important care topics such as vascular access and monitoring of
      complications. No patient identifiers were collected. RESULTS: Seventy-three
      respondents completed the first part, representing 61 teams in 20 countries. The
      median number of children on parenteral nutrition (PN) at home per team was 15
      (range 1-125). Teams consisted of the following members: paediatric
      gastroenterologist (present in 100% of the teams), dietitian (95%), specialist
      nurse (92%), paediatric surgeon (89%), pharmacist (82%), psychologist (66%),
      social worker (62%), speech therapist (48%), physiotherapist (38%), general
      paediatrician (33%). The second part was completed by 67/73 respondents (59/61
      teams). Vascular access care was comparable with the guideline. Somatostatin
      analogues were prescribed by 14% of the IF teams and probiotics by 44% of the
      teams. Prophylactic anticoagulation was used by 46% of the teams. In 81% of the
      teams a multicomponent lipid emulsion containing fish oil was routinely used.
      Bone densitometry was regularly performed in 75% of teams, but never performed in
      19%. CONCLUSIONS: In conclusion, there is a wide diversity of composition of IF
      teams and their number of patients treated. Overall, there is good compliance to
      the current guideline. Clinical practice that varied most was the standard use of
      medication such as probiotics and somatostatin analogues, and standard monitoring
      of long-term complications. Experience regarding specific treatment options
      should be shared. Moreover, international agreement on standards of care with
      focus on implementation of the guideline is needed to optimise care and improve
      outcomes of children with IF.

PMID- 29203341
TI  - In vitro to in vivo extrapolation for high throughput prioritization and decision
      making.
AB  - In vitro chemical safety testing methods offer the potential for efficient and
      economical tools to provide relevant assessments of human health risk. To realize
      this potential, methods are needed to relate in vitro effects to in vivo
      responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available
      IVIVE approaches need to be refined before they can be utilized for regulatory
      decision-making. To explore the capabilities and limitations of IVIVE within this
      context, the U.S. Environmental Protection Agency Office of Research and
      Development and the National Toxicology Program Interagency Center for the
      Evaluation of Alternative Toxicological Methods co-organized a workshop and
      webinar series. Here, we integrate content from the webinars and workshop to
      discuss activities and resources that would promote inclusion of IVIVE in
      regulatory decision-making. We discuss properties of models that successfully
      generate predictions of in vivo doses from effective in vitro concentration,
      including the experimental systems that provide input parameters for these
      models, areas of success, and areas for improvement to reduce model uncertainty.
      Finally, we provide case studies on the uses of IVIVE in safety assessments,
      which highlight the respective differences, information requirements, and
      outcomes across various approaches when applied for decision-making.

PMID- 29203344
TI  - Child Neurology Residency Program Directors and Program Coordinators 2016
      Workforce Survey.
AB  - BACKGROUND: Responsibilities of Program Directors' (PDs) and Program
      Coordinators' (PCs) roles continue to evolve within Graduate Medical Education
      (GME). METHODS: In 2016, the authors conducted an anonymous electronic survey of
      Child Neurology and Neurodevelopmental Disabilities PDs (n = 76) and PCs (n = 68)
      to address workforce characteristics, challenges related to implementing
      Accreditation Council of Graduate Medical Education (ACGME) requirements, and
      institutional support. Responses were characterized with descriptive statistics.
      RESULTS: Response rate was 72% (46 of 76 PDs, 57 of 68 PCs). PD median clinical
      workloads were five half-day clinics weekly plus three months as hospital
      attending yearly. Most PDs (61%) reported having less, and many (43%) believed
      requirements were less, protected time than the ACGME requires. Most PCs have
      clerical titles (58%), no designated GME career path (79%), inaccurate job
      descriptions (86%), little to no formal GME training (61%), work-hours exceeding
      those scheduled (68%), and time allocation below ACGME recommendations (69%).
      More than half (54%) of hourly PCs reported responding to communications after
      hours, with nearly all (92%) unpaid for such work. Shared PD-PC concerns include
      faculty completion of resident evaluations (80%), inadequate protected time
      (71%), and low PC salary (70%). For both PDs and PCs, median time in the job was
      four years. CONCLUSIONS: Child neurology and neurodevelopmental disability
      residency PDs and PCs report problems that likely increase turnover and interfere
      with training. The ACGME should consider revising, formalizing, and disseminating
      requirements for protected time for PDs and PCs, based on realistic assessments
      of current administrative requirements, and monitoring compliance as part of
      program evaluations.

PMID- 29203345
TI  - Midline Facial Defects With Associated Brain Anomaly.

PMID- 29203347
TI  - Effect of dry heat treatment on physical property and in vitro starch
      digestibility of high amylose rice starch.
AB  - The influence of dry heat treatment (DHT) of high amylose rice starch was
      investigated on starch digestibility and physical properties and their
      characteristics were compared through the PCA analysis. High amylose rice starch
      was prepared by DHT under different temperatures (110, 130, and 150 degrees C)
      and times (0, 1, 2, and 4h). The gelatinization temperature and enthalpy
      decreased as temperature and time increased, revealing the change of semi
      crystalline region. There were significant increases in gel strength and pasting
      viscosity above 130 degrees C, whereas gel strength and pasting viscosity were
      reduced with increasing heating time. On in vitro starch digestibility of DHT
      starch gel, the rapidly digestible starch and predicted glycemic index of DHT
      starches were lower than those of native starch. Both the lowest predicted
      glycemic index and the highest gel strength was observed at 130 degrees C for 1h.
      In the results of PCA analysis, the heating temperature was negatively correlated
      with in vitro starch digestibility as well as pasting viscosity and gel strength.
      These results demonstrated that DHT could be useful of enhancing the physical and
      nutritional properties of high amylose rice starch.

PMID- 29203346
TI  - FTO demethylase activity is essential for normal bone growth and bone
      mineralization in mice.

PMID- 29203348
TI  - Secretory expression of recombinant small laccase from Streptomyces coelicolor
      A3(2) in Pichia pastoris.
AB  - This work reports for the first time the secretory expression of the small
      laccase (SLAC) from Streptomyces coelicolor A3(2) in Pichia pastoris. Using an
      AOX1 promoter and alpha factor as a secretion signal, the recombinant P. pastoris
      harbouring the laccase gene (rSLAC) produced high titres of extracellular laccase
      (500 +/- 10 U/l), which were further increased seven fold by pre-incubation at 80
      degrees C for 30 min. The enzyme (~38 kDa) had an optimum activity at 80 
      degrees C, but optimum pH varied with substrate used. Km values for ABTS, SGZ and
      2,6-DMP were 142.85 MUM, 10 MUM and 54.55 MUM and the corresponding kcat values
      were 60.6 s-1, 25.36 s-1 and 27.84 s-1, respectively. The t1/2 values of the
      rSLAC at 60  degrees C, 70  degrees C, 80  degrees C were 60 h, 32 h and 10 h,
      respectively. The enzyme deactivation energy (Ed) was 117.275 kJ/mol while
      DeltaG, DeltaH and DeltaS for thermal inactivation of the rSLAC were all
      positive. The rSLAC decolourised more than 90% of Brilliant Blue G and Trypan
      Blue dye in 6 h without the addition of a mediator. High titres of SLAC expressed
      in P. pastoris enhance its potential for various industrial applications.

PMID- 29203349
TI  - Interventions to improve the uptake of cervical cancer screening among lower
      socioeconomic groups: A systematic review.
AB  - Cervical cancer is the fourth most common cancer in women worldwide. Screening
      can reduce both the incidence and mortality of the disease but is often not
      utilized by lower socioeconomic groups. A systematic review, including studies of
      interventions to improve breast and cervical cancer screening uptake, up to 2006,
      found targeted interventions could be effective. A formal update has been
      conducted on the effectiveness of interventions to improve the uptake of cervical
      cancer screening among lower socioeconomic groups. A systematic computerized
      literature search was undertaken in June 2016 for relevant papers published since
      2006. Data was extracted on study participants, setting, intervention and control
      using a predefined extraction tool and a full quality assessment was undertaken
      using the Cochrane risk of bias tool. This update yielded 16 studies of mixed
      quality, in addition to the 13 studies from the original review. The
      interventions were categorized into local interventions including HPV self
      testing, lay health advisors, inreach, outreach and mixed, and strategies
      enhancing attendance within an organized program. This review has found two
      large, randomized controlled trials for the use of HPV self-testing to increase
      cervical screening uptake. Both reviews have found varying success using lay
      health advisors, with the majority of included papers reporting a statistically
      significant increase in screening uptake. HPV self-testing can improve uptake of
      cervical cancer screening among lower socioeconomic groups. This is a relatively
      new method of cervical screening that was not included in the earlier review. The
      findings of this updated review largely support that of the 2006 review for the
      use of lay health advisors.

PMID- 29203350
TI  - Molecular characterization of a proteolytic bacterium in Panchagavya: An organic
      fertilizer mixture.
AB  - Fermented product of combination of five major substances obtained from cow,
      viz., urine, milk, ghee, curd, and dung, is known as Panchagavya. Its pro
      agricultural and medicinal value has been traditionally known to Indian farmers
      from Vedic period. In this study, the proteolytic properties of Panchagavya were
      investigated using Skim Milk Agar (SMA) form, a commercially available
      Panchagavya product. Proteolytic bacteria, SNCK-3, was successfully isolated.
      Further identification using 16s rDNA sequencing revealed that SNCK-3 belonged to
      Acinetobacter spp., which is a species of biofertilizer group. This observation
      justified the pro-agricultural role of Panchagavya. The present study represents
      primary data and it is essential to develop a new area of research for exposing
      the invisible or dormant Vedic biotechnological concepts, like Panchagavya.

PMID- 29203351
TI  - Tamarindus indica seeds improve carbohydrate and lipid metabolism: An in vivo
      study.
AB  - BACKGROUND: The tamarind seeds have a lot of nutrients that may be used to
      control cholesterol or glucose levels. OBJECTIVES: The effects of tamarind seeds
      (T) on lipid and carbohydrate metabolism in rats were studied. Rats were offered
      basal diet (BD) with T (2%, 4% or 8%) or without T. MATERIALS AND METHODS:
      Feeding and growth performance in rats were measured and samples of liver and
      blood were analyzed for glycogen content and levels of cholesterol and glucose
      respectively. RESULTS: The inclusion of T in the diet influences the feeding and
      growth performance in rats. The serum cholesterol level was reduced (p < 0.05) in
      Sprague Dawley (SD) rats fed on basal diet (BD) containing 4% and 8% T (0.24 +/-
      0.14 g/l and 0.31 +/- 0.06 g/l respectively) compared to control (0.79 +/- 0.04
      g/l). The serum glucose levels in the spontaneous hypertensive rats (SHR) was
      lower (50.74 +/- 2.50 mg/dl; p < 0.05) than control (93.52 +/- 10.83 mg/dl) at 4%
      T. Incorporation of increasing doses of T resulted in linear increase of glycogen
      storage in livers of SD rats fed on BD and high sucrose diet. CONCLUSION:
      Tamarind seeds can lower blood glucose and serum cholesterol and enhance storage
      of glycogen in rats.

PMID- 29203352
TI  - In vivo evaluation of antipyretic effects of some homeopathic ultra-high
      dilutions on Baker's yeast-induced fever on Similia principle.
AB  - BACKGROUND: Homeopathy is a controversial alternative system of medicine. The
      action of homeopathic medicines is considered slow and it is assumed that
      homeopathic medicines are ineffective in acute conditions such as fever.
      OBJECTIVE: In the present study, effects of 3 homeopathic medicines on baker's
      yeast induced fever were investigated. MATERIALS AND METHODS: 42 local strain
      rabbits were equally divided into 7 groups. Normal saline was orally administered
      to group 1 (normal control) rabbits without fever induction. Group 2 underwent
      baker's yeast-induced fever (negative control). Groups 3, 4, 5, 6 and 7 underwent
      baker's yeast-induced fever and were thereafter treated orally with paracetamol,
      Nux vomica 200C and 1M, Calcarea phos 200C and Belladonna 200C respectively.
      Rectal temperature was checked hourly. The abdominal writhing and frequency of
      loose stools were also monitored. ANOVA was applied for checking statistical
      significance. p <= 0.05 was considered significant. RESULTS: The rectal
      temperature increased significantly (p < 0.05) in the negative control group when
      compared to the normal control. Abdominal writhing and loose stools monitoring
      showed increased writhing and loose stools frequency of group 2, 3, 6 and 7
      rabbits. However, treatment of paracetamol significantly reduced rectal
      temperature. Group 4 & 5 showed significant reduction of rectal temperature
      together with abatement of abdominal writhing and loose stools. CONCLUSION: N.
      vomica ultra-high dilutions have normalized rectal temperature and prevented the
      abdominal writhing and loose stools in baker's yeast-induced fever model of
      rabbits. It could be due to antidotal activity of N. vomica ultra-high dilutions.
      Therefore, N. vomica ultra-high dilutions can be useful antipyretic agents and
      can treat conditions associated with gastrointestinal symptoms. However, fixed
      conclusion can't be asserted due to caveat of small sample size.

PMID- 29203353
TI  - Calcipotriol as pretreatment prior to daylight-mediated photodynamic therapy in
      patients with actinic keratosis: A case series.
AB  - This split-face design study evaluated the effect of pretreatment with
      calcipotriol prior to daylight-mediated photodynamic therapy (DL-PDT) in patients
      with actinic keratosis (AK). The study included 11 subjects with grade I-III AK
      (mean age: 55 years). Subjects used once-daily calcipotriol 50 mcg/g ointment on
      half the face/scalp for 15 days prior to DL-PDT. Evaluations of efficacy, safety
      and subject satisfaction were conducted 48 h and 7 days after treatment, and at 1
      and 3-month follow-ups. Three months after treatment with calcipotriol/DL-PDT
      and DL-PDT alone, the complete response rate was 85% and 70%, respectively. The
      partial response rate was 12% and 25%, respectively. During calcipotriol
      pretreatment, 6 subjects reported erythema and moderate desquamation. In 7
      subjects, calcipotriol/DL-PDT was associated with more marked erythema than that
      observed with DL-PDT alone. Eight subjects reported they preferred DL-PDT alone
      due to the inconvenience caused by the daily application of calcipotriol and the
      related erythema and desquamation. Although calcipotriol improved the efficacy of
      DL-PDT, it may not be applicable to all patients. DL-PDT is a simpler, safer and
      more convenient option than conventional-PDT. Therefore, the use of additional
      agents prolonging the course of treatment and increasing cost may diminish the
      advantages currently offered by DL-PDT.

PMID- 29203354
TI  - Unicompartmental Knee Arthroplasty vs High Tibial Osteotomy for Knee
      Osteoarthritis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Prior studies have compared unicompartmental knee arthroplasty (UKA)
      with high tibial osteotomy (HTO) suggesting that both procedures had good
      clinical outcomes. However, which treatment is more beneficial for
      unicompartmental knee osteoarthritis is still a controversy. The purpose of our
      study is to obtain postoperative outcomes of revision rate, complications,
      function results, range of motion (ROM), and pain between the 2 procedures.
      METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      (PRISMA) guidelines were followed and study protocol was published online at
      PROSPERO under registration number CRD42016049316. We searched the databases
      MEDLINE, EMBASE, Cochrane Library, and Web of Science up to May 2017. Articles
      that directly compared postoperative outcomes of UKA to HTO were included.
      RESULTS: A total of 10 comparative studies were included in our meta-analysis.
      UKA patients showed less revision rate, less complications, and less
      postoperative pain than HTO patients; however, HTO patients obtained more ROM. No
      significant difference was observed between the group accruing to the knee
      function scores and excellent/good surgical results. CONCLUSION: UKA offers a
      safe and efficient alternative to osteoarthritis reduced postoperative pain, less
      postoperative complication, and revision. The 2 surgical techniques showed
      satisfactory function results for the patients; however, the HTO group achieved
      superior ROM compared to the UKA group. HTO may be suitable for patients with
      high activity requirements. Treatment options should be carefully considered for
      each patient in accordance with their age, body mass index, grade of
      osteoarthritis, and patients' activity levels.

PMID- 29203355
TI  - A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide,
      drisapersen, in Duchenne muscular dystrophy.
AB  - This 48-week, randomized, placebo-controlled phase 3 study (DMD114044;
      NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6
      mg/kg/week in 186 ambulant boys aged >=5 years, with Duchenne muscular dystrophy
      (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was
      generally well tolerated, with injection-site reactions and renal events as most
      commonly reported adverse events. A nonsignificant treatment difference (P =
      0.415) in the change from baseline in six-minute walk distance (6MWD; primary
      efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week
      48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair
      climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings.
      Lack of statistical significance was thought to be largely due to greater data
      variability and subgroup heterogeneity. The increased standard deviation alone,
      due to less stringent inclusion/exclusion criteria, reduced the statistical power
      from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was
      performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise
      from floor. A statistically significant improvement in 6MWD of 35.4 meters (P =
      0.039) in favor of drisapersen was observed in this subpopulation. Results
      suggest that drisapersen could have benefit in a less impaired population of DMD
      subjects.

PMID- 29203357
TI  - The Health Correlates of Culture: Examining the Association Between Ethnic-Racial
      Identity and Diurnal Cortisol Slopes.
AB  - PURPOSE: The objective of this study was to examine the link between ethnic
      racial identity (ERI) components (exploration, resolution, and affirmation) and
      youths' diurnal cortisol slopes. METHODS: A sample of 103 U.S.-Mexican
      adolescents (Mage = 15.29 years) living in the Southwest participated in an in
      home interview and 3-day salivary sampling protocol. RESULTS: ERI affirmation,
      but not exploration or resolution, was related to steeper diurnal slopes (greater
      declines in cortisol from waking to bedtime) after controlling for adolescents'
      life stressors, acculturation level, ethnic-racial discrimination, and daily
      behaviors (i.e., caffeine use, hours of exercise, hours of sleep, and medication
      level). CONCLUSIONS: This study provides initial evidence of the physiological
      benefits of ERI affirmation. Given that steeper diurnal slopes are thought of as
      an indicator of positive health, our findings point to the importance of
      examining cultural processes in the well-being of ethnic-racial minority youth.

PMID- 29203356
TI  - 226th ENMC International Workshop:: Towards validated and qualified biomarkers
      for therapy development for Duchenne muscular dystrophy 20-22 January 2017,
      Heemskerk, The Netherlands.

PMID- 29203358
TI  - Dietary Fish Oil Supplementation Enhances Expression of Genes Involved in
      Cornified Cell Envelope Formation in Rat Skin.

PMID- 29203359
TI  - Bone Marrow-Derived Stem Cells Migrate into Intraepidermal Skin Defects of a
      Desmoglein-3 Knockout Mouse Model but Preserve their Mesodermal Differentiation.
AB  - Inherited forms of epidermolysis bullosa are blistering diseases of the skin and
      mucosa resulting from various gene mutations. Transplantation of bone marrow
      derived stem cells might be a promising systemic treatment for severe dystrophic
      or junctional epidermolysis bullosa, but many key questions remain unresolved.
      Two open questions of clinical interest are whether systemically transplanted
      bone marrow-derived stem cells of mesodermal origin might be able to
      transdifferentiate into keratinocytes with an ectodermal phenotype and whether
      these cells are also capable of repairing a specific intraepidermal gene defect.
      To address these questions, we transplanted bone marrow-derived stem cells into
      mice with a blistering disease exclusively localized to the epidermis resulting
      from a functional knockout of desmoglein-3 (Dsg3). We found that Dsg3+ donor
      derived cells migrate into the recipient epidermis. However, these cells failed
      to restore the missing Dsg3 mRNA and DSG3 protein expression in the transplanted
      Dsg3-/- mice. The donor-derived cells found in the epidermis preserved their
      CD45+ hematopoietic origin, and no transdifferentiation into integrin alpha6+
      keratinocytes or integrin alpha6+/CD34+ epidermal stem cells occurred. Our
      results indicate that bone marrow-derived stem cells preserve their mesodermal
      fate after systemic transplantation and are not capable of treating patients with
      epidermolysis bullosa with an intraepidermal skin defect.

PMID- 29203360
TI  - The Genetics of Seborrheic Dermatitis: A Candidate Gene Approach and Pilot Genome
      Wide Association Study.

PMID- 29203361
TI  - Extracellular Vesicles as Biomarkers for the Detection of a Tumor Marker Gene in
      Epidermolysis Bullosa-Associated Squamous Cell Carcinoma.

PMID- 29203362
TI  - HLA-DQB1*03:01 as a Biomarker for Genetic Susceptibility to Bullous Pemphigoid
      Induced by DPP-4 Inhibitors.

PMID- 29203363
TI  - Mechanism of Action of G-Quadruplex-Forming Oligonucleotide Homologous to the
      Telomere Overhang in Melanoma.
AB  - T-oligo, a guanine-rich oligonucleotide homologous to the 3'-telomeric overhang
      of telomeres, elicits potent DNA-damage responses in melanoma cells; however, its
      mechanism of action is largely unknown. Guanine-rich oligonucleotides can form G
      quadruplexes (G4), which are stabilized by the hydrogen bonding of guanine
      residues. In this study, we confirmed the G4-forming capabilities of T-oligo
      using nondenaturing PAGE, nuclear magnetic resonance, and immunofluorescence.
      Using an anti-G-quadruplex antibody, we showed that T-oligo can form G4 in the
      nuclei of melanoma cells. Furthermore, using DNase I in a nuclease degradation
      assay, G4-T-oligo was found to be more stable than single-stranded T-oligo. G4-T
      oligo had decreased antiproliferative effects compared with single-stranded T
      oligo. However, G4-T-oligo has similar cellular uptake as single-stranded T
      oligo, as shown by FACS analysis. Inhibition of JNK, which causes DNA damage
      induced apoptosis, partially reversed the antiproliferative activity of T-oligo.
      T-oligo also inhibited mRNA expression of human telomerase reverse transcriptase,
      a catalytic subunit of telomerase that was reversed by JNK inhibition.
      Furthermore, two shelterin complex proteins TRF2/POT1 were found to be up
      regulated and bound by T-oligo, suggesting that T-oligo may mediate dissociation
      of these proteins from the telomere overhang. These studies show that T-oligo can
      form a G-quadruplex and that the antitumor effects of T-oligo may be mediated
      through POT1/TRF2 and via human telomerase reverse transcriptase inhibition
      through JNK activation.

PMID- 29203364
TI  - The presence of IL-8 +781 T/C polymorphism is associated with the parameters of
      severe Clostridium difficile infection.
AB  - PURPOSE: There is large variation in the clinical manifestations of Clostridium
      difficile infection (CDI). We also still can not predict which patients are more
      susceptible to reinfection with CDI. The aim of our study was to evaluate the
      effect of gene single nucleotide polymorphisms (SNP) of proinflammatory
      cytokines, specifically IL-1beta, IL-8 on the development, clinical course and
      recurrence of CDI. METHODS: We performed a prospective study of adults (130
      people >= 18 years) including 65 patients with CDI treated in tertiary hospital
      and 65 healthy persons. The following 3 variants were analyzed for the occurrence
      of gene polymorphisms in patients with CDI versus the control group: IL-1beta
      +3953 A/G (rs1143634), IL-1beta -31 A/G (rs1143627), and IL-8 +781 T/C
      (rs2227306). Then, we assessed the correlation between these genetic
      polymorphisms and biochemical parameters important in CDI course, CDI severity as
      well as CDI recurrence. RESULTS AND CONCLUSIONS: The presence of genetic
      polymorphisms of IL-1beta +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an
      effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C
      polymorphism is associated with the severe CDI.

PMID- 29203366
TI  - Commentary to 'Reduction and standardization of surgical instruments in pediatric
      inguinal hernia repair'.

PMID- 29203365
TI  - Antibacterial activities, phytochemical analysis and chemical composition
      Makhlaseh extracts against the growth of some pathogenic strain causing poisoning
      and infection.
AB  - The aim of this study was to investigate the antibacterial activities and
      phytochemical analysis of extracts against the growth of some pathogenic strain
      causing poisoning and infection (Staphylococcus aureus, Streptococcus pyogenes,
      Staphylococcus epidermidis, Enterobacter aerogenes, Escherichia coli and Shigella
      flexneri). Makhlaseh components were identified via gas chromatography/mass
      spectrometry (GC/MS). Total phenolic content (TPC), alkaloids, tannins and
      saponins were determined. Antioxidant activity was determined calorimetrically
      for 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. Antimicrobial
      effect of extracts was evaluated by five methods, pour plate, well diffusion,
      disk diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal
      concentration (MBC). Camphor was the major compound of Makhlaseh. The TPC of
      aqueous and ethanolic Makhlaseh extracts was equal to 79.45 +/- 1.15 and 115.26
      +/- 1.23 MUg GAE/mg, respectively. The antioxidant activity (IC50) test of
      aqueous and ethanolic Makhlaseh extracts showed 315.50 +/- 1.12 and 118.35 +/-
      1.08 MUg/ml, respectively. MIC of the aqueous extract of Makhlaseh for
      Enterobacter aerogenes, Escherichia coli, Shigella flexneri, Staphylococcus
      aureus, Staphylococcus epidermidis and Streptococcus pyogenes were 32, 32, 16,
      16, 8 and 8 mg/ml, respectively, and the MIC of the ethanolic extract were 16,
      16, 16, 8, 4, and 4 mg/ml, respectively. The MBCs of the Makhlaseh extracts
      varied from 4 mg/ml to 128 mg/ml. Increasing concentration of Makhlaseh extracts
      had a significant effect (p <= 0.05) on inhibition zone diameter. In conclusion,
      using Makhlaseh extracts as a natural antibacterial composite in vitro have
      significant antibacterial ability over the studied strains.

PMID- 29203367
TI  - Cross-talk between hydrogen sulfide and carbon monoxide in the mechanism of
      experimental gastric ulcers healing, regulation of gastric blood flow and
      accompanying inflammation.
AB  - Hydrogen sulfide (H2S) and carbon monoxide (CO) exert gastroprotection against
      acute gastric lesions. We determined the cross-talk between H2S and CO in gastric
      ulcer healing process and regulation of gastric blood flow (GBF) at ulcer margin.
      Male Wistar rats with acetic acid-induced gastric ulcers were treated i.g.
      throughout 9 days with vehicle (control), NaHS (0.1-10 mg/kg) +/- zinc
      protoporphyrin (ZnPP, 10 mg/kg), d,l-propargylglycine (PAG, 30 mg/kg), CO
      releasing CORM-2 (2.5 mg/kg) +/- PAG. GBF was assessed by laser flowmetry, ulcer
      area was determined by planimetry/histology. Gastric mucosal H2S production was
      analysed spectrophotometrically. Protein and/or mRNA expression at ulcer margin
      for vascular endothelial growth factor (VEGF)A, epidermal growth factor receptor
      (EGFr), cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS), 3
      mercaptopyruvate sulfurtransferase (3-MST), heme oxygenases (HOs), nuclear factor
      (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-2, inducible nitric
      oxide synthase (iNOS), IL-1beta, TNF-alpha and hypoxia inducible factor (HIF)
      1alpha were determined by real-time PCR or western blot. IL-1alpha, IL-1beta, IL
      2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IFN-gamma, TNF-alpha, GM-CSF plasma
      concentration was assessed using Luminex platform. NaHS dose-dependently
      decreased ulcer area and increased GBF but ZnPP attenuated these effects. PAG
      decreased H2S production but failed to affect CORM-2-mediated ulcer healing and
      vasodilation. NaHS increased Nrf-2, EGFr, VEGFA and decreased pro-inflammatory
      markers expression and IL-1beta, IL-2, IL-13, TNF-alpha, GM-CSF plasma
      concentration. CORM-2 decreased IL-1beta and GM-CSF plasma levels. We conclude
      that NaHS accelerates gastric ulcer healing increasing microcirculation and Nrf
      2, EGFr, VEGFA expression. H2S-mediated ulcer healing involves endogenous CO
      activity while CO does not require H2S. NaHS decreases systemic inflammation more
      effectively than CORM-2.

PMID- 29203368
TI  - Modulating autophagy in cancer therapy: Advancements and challenges for cancer
      cell death sensitization.
AB  - Autophagy is a major protein degradation pathway capable of upholding cellular
      metabolism under nutrient limiting conditions, making it a valuable resource to
      highly proliferating tumour cells. Although the regulatory machinery of the
      autophagic pathway has been well characterized, accurate modulation of this
      pathway remains complex in the context of clinical translatability for improved
      cancer therapies. In particular, the dynamic relationship between the rate of
      protein degradation through autophagy, i.e. autophagic flux, and the
      susceptibility of tumours to undergo apoptosis remains largely unclear. Adding to
      inefficient clinical translation is the lack of measurement techniques that
      accurately depict autophagic flux. Paradoxically, both increased autophagic flux
      as well as autophagy inhibition have been shown to sensitize cancer cells to
      undergo cell death, indicating the highly context dependent nature of this
      pathway. In this article, we aim to disentangle the role of autophagy modulation
      in tumour suppression by assessing existing literature in the context of
      autophagic flux and cellular metabolism at the interface of mitochondrial
      function. We highlight the urgency to not only assess autophagic flux more
      accurately, but also to center autophagy manipulation within the unique and
      inherent metabolic properties of cancer cells. Lastly, we discuss the challenges
      faced when targeting autophagy in the clinical setting. In doing so, it is hoped
      that a better understanding of autophagy in cancer therapy is revealed in order
      to overcome tumour chemoresistance through more controlled autophagy modulation
      in the future.

PMID- 29203370
TI  - Pregnancy Around the Clock.
AB  - A recent study introduced the existence of an 'immune clock' in pregnancy; during
      the course of gestation, peripheral blood cells from pregnant women were analyzed
      by mass cytometry using a single-cell signaling-based elastic net algorithm. The
      insights will undoubtedly promote the testing of such a clock - possibly in
      synergy with other pacemakers - to potentially predict pregnancy complications.

PMID- 29203369
TI  - Gasotransmitter hydrogen sulfide signaling in neuronal health and disease.
AB  - Hydrogen sulfide is a gaseous signaling molecule or gasotransmitter which plays
      important roles in a wide spectrum of physiologic processes in the brain and
      peripheral tissues. Unlike nitric oxide and carbon monoxide, the other major
      gasotransmitters, research on hydrogen sulfide is still in its infancy. One of
      the modes by which hydrogen sulfide signals is via a posttranslational
      modification termed sulfhydration/persulfidation, which occurs on reactive
      cysteine residues on target proteins, where the reactive SH group is converted to
      an SSH group. Sulfhydration is a substantially prevalent modification, which
      modulates the structure or function of proteins being modified. Thus, precise
      control of endogenous hydrogen sulfide production and metabolism is critical for
      maintenance of optimal cellular function, with excess generation and paucity,
      both contributing to pathology. Dysregulation of the reverse transsulfuration
      pathway which generates hydrogen sulfide occurs in several neurodegenerative
      diseases such as Parkinson's disease, Huntington's disease and Alzheimer's
      disease. Accordingly, treatment with donors of hydrogen sulfide or stimulation of
      the reverse transsulfuration have proved beneficial in several neurodegenerative
      states. In this review we focus on hydrogen sulfide mediated neuronal signaling
      processes that contribute to neuroprotection.

PMID- 29203371
TI  - High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway
      in keratinocytes: A potential mechanism and therapeutic target for diabetic small
      fiber neuropathy.
AB  - Small fiber neuropathy (SFN) is a common complication in diabetes, and is
      characterized by decreased intraepidermal nerve fiber density (IENFD). Semaphorin
      3A (Sema3A), which is produced by keratinocytes, has a chemorepulsive effect on
      intraepidermal nerve fibers. mTOR signaling can mediate local protein synthesis
      that is critical for growth of axons and dendrites. Therefore, this study aimed
      to investigate whether Sema3A is up-regulated in diabetic keratinocytes via the
      mTOR-mediated p70 S6K and 4E-BP1 signaling pathways, and furthermore whether it
      is involved in the pathogenesis of diabetic SFN. IENFD, expression of Sema3A, and
      mTOR signaling, were evaluated in the skin of diabetic patients with SFN as well
      as control subjects. Sema3A and mTOR signaling were also assessed in HaCaT cells
      which had been treated with high glucose (HG) or recombinant Sema3A (rSema3A) in
      the presence or absence of rapamycin. Small fiber dysfunction was evaluated by
      examining IENFD and using behavioral tests in control and streptozotocin-induced
      diabetic rats treated with or without rapamycin. We found that higher Sema3A
      expression and over-activation of mTOR signaling, was accompanied by reduced
      IENFD in the skin of diabetic patients compared with control subjects. The
      expression of Sema3A, and mTOR signaling were up-regulated in HaCaT cells
      incubated with HG or rSema3A, and this could be attenuated by rapamycin.
      Hyperalgesia, reduced IENFD, and up-regulated Sema3A and mTOR signaling were also
      detected in diabetic rats. These effects were ameliorated by rapamycin treatment.
      Our data indicate that HG up-regulates Sema3A expression by activating mTOR
      signaling in diabetic keratinocytes. This pathway may therefore play a critical
      role in diabetic SFN.

PMID- 29203372
TI  - ROS production and glutathione response in keratinocytes after application of
      beta-carotene and VIS/NIR irradiation.
AB  - The skin is exposed to many stress factors which, in turn, can promote a shift of
      the antioxidant (AO) network towards the prooxidative side, supporting the
      development of various skin disorders. A balanced diet, in combination with a
      healthy lifestyle could reduce oxidative stress. Carotenoids are essential
      nonenzymatic AOs and main components of the exogenous AO system. To examine the
      interdependence between endogenous and exogenous AOs, secondary keratinocytes
      (HaCaT) were treated with various Beta (beta-)-carotene concentrations with
      subsequent stress treatment by moderate irradiation (700-2000 nm). To facilitate
      the uptake of beta-carotene, an innovative nanocrystal solution was used. Cell
      viability assay was applied to HaCaT cells to evaluate suitable concentration of
      beta-carotene, whereby the uptake was measured by resonant Raman spectroscopy.
      The redox status was determined before and after supplementation with two
      selected beta-carotene concentrations (0.02 and 0.1 MUg/ml) and irradiation.
      Reactive oxygen species (ROS) were measured by electron paramagnetic resonance
      spectroscopy and the AO glutathione (GSH) by a fluorescent-based assay for
      evaluating the endogenous redox status. An increase of ROS and a reduction of GSH
      after irradiation was observed. Interestingly, the applied beta-carotene, already
      induce oxidative stress. Nevertheless, an effective protection against
      irradiation could be observed for the lower dose. The high dose turned pro
      oxidative.

PMID- 29203373
TI  - Betulinic, oleanolic and ursolic acids inhibit the enzymatic and biological
      effects induced by a P-I snake venom metalloproteinase.
AB  - Betulinic acid (BA), Oleanolic acid (OA) and Ursolic acid (UA), are pentacyclic
      triterpenoids with widespread occurrence throughout the plant kingdom, these
      compounds are widely recognized by their pharmacological and biological
      properties, such as, anti-tumoral, anti-inflammatory, anti-microbial and
      hepatoprotective activity. In this work we determined the inhibitory ability of
      these compounds on the enzymatic, hemorrhagic, myotoxic and edema-inducing
      activities of Batx-I, a P-I metalloproteinase isolated from Bothrops atrox venom.
      BA, UA and OA inhibited the proteolytic activity of Batx-I on gelatin with IC50
      values of 115.3, 223.0 and 357.3 MUM, respectively. Additionally, these compounds
      showed inhibition of the hemorrhagic activity of Batx-I in skin with IC50 345.7,
      643.5 and 1077.0 MUM for BA, UA and OA in preincubation experiments. In studies
      with independent-injection, in which Batx-I was injected and then, at the same
      site, a concentration of 600 MUM of each compound were administered at either 0,
      5 or 10 min, BA showed a significant reduction of hemorrhage at 0 and 5 min. In
      addition, these compounds inhibited myotoxicity and edema-forming activity of
      Batx-I at 600 MUM concentration. Molecular docking studies suggested that these
      compounds could occupy part of the substrate binding cleft of the enzyme
      affecting its catalytic cycle. In this manner, triterpenic acids are candidates
      for the development of inhibitors for the prevention of local tissue damage in
      snakebite envenomation.

PMID- 29203374
TI  - Crystal structure of UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) from
      Mycobacterium tuberculosis.
AB  - The biosynthesis of UDP-N-acetylmuramic acid (UDP-MurNAc) by reduction of UDP-N
      acetylglucosamine-enolpyruvate (UDP-GlcNAc-EP) in an NADPH and FAD-dependent
      reaction in bacteria is one of the key steps in peptidoglycan biosynthesis
      catalyzed by UDP-N-acetylglucosamine-enolpyruvate reductase (MurB). Here, we
      present the crystal structure of Mycobacterium tuberculosis MurB (MtbMurB) with
      FAD as the prosthetic group at 2.0A resolution. There are six molecules in
      asymmetric unit in the form of dimers. Each protomer can be subdivided into three
      domains and the prosthetic group, FAD is bound in the active site between domain
      I and domain II. Comparison of MtbMurB structure with the structures of the
      Escherichia coli MurB (in complex with UDP-GlcNAc-EP) and Pseudomonas aeruginosa
      MurB (in complex with NADPH) showed all three structures share similar domain
      architecture and residues in the active site. The nicotinamide and the enol
      pyruvyl moieties are well aligned upon superimposition, both positioned in
      suitable position for hydride transfer to and from FAD. The comparison studies
      and MD simulations demonstrate that the two lobes of domain-III become more
      flexible. The substrates (NADPH and UDP-GlcNAc-EP) binding responsible for open
      conformation of MurB, suggesting that NADPH and UDP-GlcNAc-EP interactions are
      conformationally stable. Our findings provide a detail mechanism about the closed
      to open state by binding of NADPH and UDP-GlcNAc-EP induces the conformational
      changes of MurB structure that may trigger the MurB catalytic reaction.

PMID- 29203376
TI  - Corrigendum to "Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase
      and Histone Deacetylase as a Therapy for Colorectal Cancer" (EBioMedicine Aug
      2016; 10: 124-36).

PMID- 29203375
TI  - Free energy calculations on the stability of the 14-3-3zeta protein.
AB  - Mutations of cysteine are often introduced to e.g. avoid formation of non
      physiological inter-molecular disulfide bridges in in-vitro experiments, or to
      maintain specificity in labeling experiments. Alanine or serine is typically
      preferred, which usually do not alter the overall protein stability, when the
      original cysteine was surface exposed. However, selecting the optimal mutation
      for cysteines in the hydrophobic core of the protein is more challenging. In this
      work, the stability of selected Cys mutants of 14-3-3zeta was predicted by free
      energy calculations and the obtained data were compared with experimentally
      determined stabilities. Both the computational predictions as well as the
      experimental validation point at a significant destabilization of mutants C94A
      and C94S. This destabilization could be attributed to the formation of
      hydrophobic cavities and a polar solvation of a hydrophilic side chain. A L12E,
      M78K double mutant was further studied in terms of its reduced dimerization
      propensity. In contrast to naive expectations, this double mutant did not lead to
      the formation of strong salt bridges, which was rationalized in terms of a
      preferred solvation of the ionic species. Again, experiments agreed with the
      calculations by confirming the monomerization of the double mutants. Overall, the
      simulation data is in good agreement with experiments and offers additional
      insight into the stability and dimerization of this important family of
      regulatory proteins.

PMID- 29203377
TI  - Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A
      Consensus Proposal.
AB  - Cancer evolution is a step-wise non-linear process that may start early in life
      or later in adulthood, and includes pre-malignant (indolent) and malignant
      phases. Early somatic changes may not be detectable or are found by chance in
      apparently healthy individuals. The same lesions may be detected in pre-malignant
      clonal conditions. In some patients, these lesions may never become relevant
      clinically whereas in others, they act together with additional pro-oncogenic
      hits and thereby contribute to the formation of an overt malignancy. Although
      some pre-malignant stages of a malignancy have been characterized, no global
      system to define and to classify these conditions is available. To discuss open
      issues related to pre-malignant phases of neoplastic disorders, a working
      conference was organized in Vienna in August 2015. The outcomes of this
      conference are summarized herein and include a basic proposal for a nomenclature
      and classification of pre-malignant conditions. This proposal should assist in
      the communication among patients, physicians and scientists, which is critical as
      genome-sequencing will soon be offered widely for early cancer-detection.

PMID- 29203378
TI  - Occurrence of Acanthamoeba genotypes in Central West Malaysian environments.
AB  - Acanthamoeba species are ubiquitous free-living protozoa that can be found
      worldwide. Occasionally, it can become parasitic and the causative agent of
      acanthamoebic keratitis (AK) and Granulomatous Amoebic Encephalitis (GAE) in man.
      A total of 160 environmental samples and 225 naturally-infected animal corneal
      swabs were collected for Acanthamoeba cultivation. Acanthamoeba was found to be
      high in samples collected from environments (85%, 136/160) compared to infected
      animal corneas (24.89%, 56/225) by microscopic examination. Analysis of
      nucleotide sequence of 18S rRNA gene of all the 192 cultivable Acanthamoeba
      isolates revealed 4 genotypes (T3, T4. T5 and T15) with T4 as the most prevalent
      (69.27%, 133/192) followed by T5 (20.31%), T15 (9.90%) and T3 (0.52%). Genotype
      T4 was from the strain of A. castellanii U07401 (44.27%), A. castellanii U07409
      (20.83%) and A. polyphagaAY026243 (4.17%), but interestingly, only A. castellanii
      U07401 was detected in naturally infected corneal samples. In environmental
      samples, T4 was commonly detected in all samples including dry soil, dust, wet
      debris, wet soil and water. Among the T4, A. castellanii (U07409) strains were
      detected high occurrence in dry (45%) followed by aquatic (32.50%) and moist
      (22.50%) samples but however A. castellanii (U07401) strains were dominant in dry
      samples of soil and dust (93.10%). Subsequently, genotype T5 of A. lenticulata
      (U94741) strains were dominant in samples collected from aquatic environments
      (58.97%). In summary, A. castellanii (U07401) strains were found dominant in both
      environmental and corneal swab samples. Therefore, these strains are possibly the
      most virulent and dry soil or dusts are the most possible source of Acanthamoeba
      infection in cats and dogs corneas.

PMID- 29203379
TI  - Arthroscopic Reconstruction of the Ligamentum Teres: A Guide to Safe Tunnel
      Placement.
AB  - PURPOSE: To provide a quantitative guide to tunnel placement concurrently through
      the femur and acetabulum during a ligamentum teres reconstruction, minimizing the
      risk of injury to the obturator neurovascular bundle. METHODS: Nine human
      cadaveric pelvises, complete with femurs (mean age, 59.6 years; age range, 47-65
      years), were studied. Before dissection, a 3-dimensional coordinate-measuring
      device was used to record the neutral orientation of the femur in the acetabulum.
      The specimens were then dissected free of all extra-articular soft tissue, except
      for the ligamentum teres and the obturator neurovascular bundle, and digitized.
      An anatomic femoral reconstruction tunnel through the femoral neck was simulated
      and extended along its axis into the acetabulum. The femur was digitally rotated
      internally from 0 degrees  to 30 degrees  and externally from 0 degrees  to 40
      degrees , as well as abducted from 0 degrees  to 30 degrees  and adducted from 0
      degrees  to 20 degrees , in increments of 1 degrees . At each position, the
      location of the simulated acetabular reconstruction tunnel was measured with
      respect to the obturator bundle and the edge of the acetabular fossa. RESULTS:
      The anatomic reconstruction tunnel entered the lateral side of the femur at a
      mean distance of 7.0 mm distal and 5.8 mm anterior to the center of the vastus
      ridge. By angling the femur at 15 degrees  of internal rotation and 15 degrees 
      of abduction, the obturator neurovascular bundle was avoided in 100% of
      specimens. CONCLUSIONS: The most important finding of this study was that a
      ligamentum teres reconstruction tunnel could be reamed through the femoral neck
      and safely positioned in the acetabulum by angling the femur at 15 degrees  of
      internal rotation and 15 degrees  of abduction. CLINICAL RELEVANCE: These
      quantitative descriptions of the ligamentum teres reconstruction tunnels can be
      used to guide arthroscopic surgical interventions designed to address ligamentum
      teres pathology.

PMID- 29203380
TI  - Periarticular Injection Versus Femoral Nerve Block for Pain Relief After Anterior
      Cruciate Ligament Reconstruction: A Randomized Controlled Trial.
AB  - PURPOSE: To compare the effectiveness and safety of periarticular injection (PI)
      with those of femoral nerve block (FNB) after anterior cruciate ligament (ACL)
      reconstruction. METHODS: A total of 129 patients scheduled for ACL reconstruction
      were randomly assigned to receive PI or FNB. Other perioperative interventions
      were identical for all patients. The primary outcome was the postoperative pain
      score 24 hours after surgery, which was measured using a 100-mm visual analog
      scale (VAS). The pain scores were also assessed to determine whether the VAS
      score would reach the threshold values reported for the minimal clinically
      important difference (MCID) and patient acceptable symptomatic state (PASS).
      RESULTS: The PI group had significantly lower VAS scores 24 hours after ACL
      reconstruction than the FNB group (21 mm vs 39 mm; P < .0001). Consequently, the
      primary outcome reached the level of clinical significance as indicated by the
      threshold values of an MCID of 9.9 and a PASS of 33. The PI group also had a
      significantly lower VAS score at rest at 4 hours, 8 hours, and 2 days after
      surgery (30 mm vs 39 mm [P = .025], 25 mm vs 33 mm [P = .022], and 22 mm vs 32 mm
      [P = .0022], respectively). The opioid consumption during the initial 24 hours
      was significantly lower in the PI group (354 MUg vs 503 MUg; P = .0003). The
      complication rate, including opioid-related complications, was not significantly
      different between groups. CONCLUSION: The patients treated with PI had
      significantly better pain scores and lower opioid consumption than those treated
      with FNB without elevating the complication rate. LEVEL OF EVIDENCE: Level I,
      randomized controlled trial.

PMID- 29203381
TI  - Accuracy of 3 Clinical Tests to Diagnose Proximal Hamstrings Tears With and
      Without Sciatic Nerve Involvement in Patients With Posterior Hip Pain.
AB  - PURPOSE: To determine the diagnostic accuracy of the active hamstring test at 30
      degrees  (A-30) and 90 degrees  (A-90) of knee flexion, the long stride heel
      strike (LSHS) test, and combination of the 3 tests for individuals with hamstring
      tendon tears, with and without sciatic nerve involvement. METHODS: A
      retrospective review of 564 consecutive clinical records identified 42 subjects
      with a mean age of 50.31 +/- 15 years who underwent a standard physical
      examination prior to magnetic resonance imaging (MRI) evaluation and diagnostic
      injection for posterior hip. The physical examination included the A-30, A-90,
      and LSHS tests. Sensitivity, specificity, positive likelihood ratio, negative
      likelihood ratio, and diagnostic odds ratio were calculated to determine the
      diagnostic accuracy of these 3 tests. RESULTS: Forty-two subjects (female = 32
      and male = 10) with a mean age of 50.31 years (range 15-77, +/- SD 14.52) met the
      inclusion criteria and were included in the review. Based on MRI and/or
      injection, 64.28% (27/42) of subjects were diagnosed with hamstring tear.
      Fourteen (51.85%) presented with sciatic nerve involvement. The sensitivity,
      specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic
      odds ratio for each test were as follows: A-30 knee flexion: 0.73, 0.97, 23.43,
      0.28, and 84.73; A-90 knee flexion: 0.62, 0.97, 20.00, 0.39, and 51.67; LSHS:
      0.55, 0.73, 2.08, 0.61, and 3.44. The most accurate findings were obtained when
      the results of the A-30 and A-90 were combined, with sensitivity, specificity,
      positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio
      of 0.84, 0.97, 26.86, 0.17, and 161.89, respectively. CONCLUSION: The combination
      of the active hamstring A-30 and A-90 tests proved to be a highly accurate and
      valuable tool to diagnose proximal hamstring tendons tears with or without
      sciatic nerve involvement in subjects presenting with posterior hip pain. LEVEL
      OF EVIDENCE: Level III, diagnostic study.

PMID- 29203382
TI  - Thirteen years' experience of 893 PGD cycles for monogenic disorders in a
      publicly funded, nationally regulated regional hospital service.
AB  - This study provides an overview of preimplantation genetic diagnosis (PGD) for
      single gene diseases and the management of expanding indications in the context
      of a fully financially covered service at Montpellier's regional hospital centre.
      Within the framework of a restrictive law ruling PGD in France, only the parental
      genetic risk can be studied in embryos (concurrent aneuploidy screening is not
      allowed). PCR-based techniques were developed combining mutation detection and
      closely linked short tandem repeat markers within or flanking the affected genes,
      and set up more than 100 different robust fluorescent multiplex assays for 61
      monogenic disorders. This strategy was used to analyse blastomeres from cleavage
      stage embryos. Overall, 893 cycles were initiated in 384 couples; 727 cycles
      proceeded to oocyte retrieval and 608 cycles to embryo transfer, resulting in 184
      deliveries. Clinical pregnancy rate per transfer, implantation and miscarriage
      rates were 33.6%, 25.1% and 8.8%, respectively. Our PGD programme resulted in the
      birth of 214 healthy babies for 162 out of 358 couples (45.3%), constituting a
      relevant achievement within an organizational framework that does not allow
      aneuploidy screening but provides equal access to PGD, both geographically and
      socioeconomically. This is a rare example of a fully free-of-charge PGD service.

PMID- 29203383
TI  - Comprehensive chromosomal and mitochondrial copy number profiling in human IVF
      embryos.
AB  - Single cell whole genome sequencing helps to decipher the genome heterogeneity
      within a cell population and facilitates the analysis of trace amounts of genetic
      material, such as is found in human embryos. The mitochondrial genome, although
      an important part of the genetic composition of eukaryotic cells, is often
      neglected in single cell genome analysis. A recently developed single cell whole
      genome amplification method was used, known as multiple annealing and looping
      based amplification cycles (MALBAC-NGS), for simultaneous analysis of chromosomal
      and mitochondrial genomes at the single cell level. The platform was validated by
      a series of technical and biological replicates and used for chromosomal and
      mitochondrial copy number analysis in 399 in-vitro fertilized embryos from 81
      couples. A positive correlation of maternal age with increased mitochondria
      quantity (beta = 0.176, P = 0.001) was observed after adjusting for the impact of
      cell type. Lower numbers of mitochondria were detected in successfully implanted
      embryos, although the difference was not significant. It is proposed that MALBAC
      NGS could potentially be used for an advanced pre-implantation genetic screening
      procedure with both chromosomal constitution and mitochondrial copy number being
      evaluated.

PMID- 29203384
TI  - Do endometriomas grow during ovarian stimulation for assisted reproduction? A
      three-dimensional volume analysis before and after ovarian stimulation.
AB  - Whether endometriomas grow because of supraphysiological oestradiol levels
      attained during ovarian stimulation for assisted reproduction techniques is a
      concern. In this prospective study, 25 women with 28 endometriomas underwent
      three-dimensional ultrasound using sono-automated volume calculation software.
      Endometrioma volume was measured on the first day of gonadotrophin injection (V1)
      and the day of ovulation trigger (V2). Nine (36%) women were stimulated in a
      gonadotrophin releasing hormone antagonist protocol (GnRH), 13 (52%) in a long,
      and three (12%) in an ultra-long GnRH agonist protocol. Mean duration of
      stimulation was 10.3 days with median total gonadotrophin dose of 4500 IU/day.
      Median number of cumulus oocyte complexes was five, and metaphase-two oocytes was
      four. None of the endometriomas were punctured during oocyte retrieval. Median V1
      was 22.2 ml (12-30 ml) and median V2 was 24.99 ml (11.2-37.4 ml) with P = 0.001.
      Twenty-three out of 28 endometriomas (82%) grew to some extent during ovarian
      stimulation. Endometrioma growth was positively correlated with prestimulation
      cyst volume (Correlation coefficient 0.664; P < 0.01). Although the 3-ml average
      growth was statistically significant, it could be regarded as clinically
      insignificant.

PMID- 29203385
TI  - The effect of DNA-PKcs gene silencing on proliferation, migration, invasion and
      apoptosis, and in vivo tumorigenicity of human osteosarcoma MG-63 cells.
AB  - The purpose of this study was to explore the role by which the DNA-dependent
      protein kinase complex catalytic subunit (DNA-PKcs) influences osteosarcoma MG-63
      cell apoptosis, proliferation, migration and invasion. Osteosarcoma tissues and
      adjacent normal tissues were obtained from 57 osteosarcoma patients. Human
      osteosarcoma MG-63 cells were assigned into designated groups including the
      blank, siRNA-negative control (NC) and siRNA-DNA-PKcs groups. RT-qPCR and Western
      blotting methods were employed to evaluate the mRNA and protein expressions of
      DNA-PKcs. A cell counting kit-8 (CCK-8) assay was performed to assess cell
      viability. The evaluation of cell migration and invasion were conducted by means
      of Scratch test and Transwell assay. Flow cytometry with PI and annexin V/PI
      double staining was applied for the analysis of the cell cycle and apoptosis.
      Twenty-Four Balb/c nude mice were recruited and randomly divided into the blank,
      siRNA-NC and siRNA-DNA-PKcs groups. Tumorigenicity of the Balb/c nude mice was
      conducted to evaluate the rate of tumor formation, as well as for the assessment
      of tumor size and weight, and confirm the number of lung metastatic nodules in
      the mice post transfection. Osteosarcoma tissues were found to possess greater
      expression of DNA-PKcs than that of the adjacent normal tissues. DNA-PKcs
      expression in osteosarcoma tissues were correlated with the clinical stage and
      metastasis. Compared with the blank and siRNA-NC groups, proliferation, miration,
      as well as the invasion abilities of the MG-63 cells increased. Furthermore, an
      increase in apoptosis and cells at the G1 stage in the MG-63 cells was observed,
      while there were reductions in the cells detected at the S stage. The mRNA and
      protein expressions of CyclinD1, PCNA, Bcl-2 decreased while those of Bax
      increased in the siRNA-DNA-PKcs group. The tumor formation rate, tumor diameter,
      weight and lung metastatic nodules among the nude mice in the siRNA-DNA-PKcs
      group were all lower than those in the blank and siRNA-NC groups. The
      observations and findings of the study suggested that the silencing of DNA-PKcs
      inhibits the proliferation, migration and invasion, while acting to promote cell
      apoptosis in MG-63 cells and osteosarcoma growth in nude mice.

PMID- 29203386
TI  - Procalcitonin: The marker of pediatric bacterial infection.
AB  - Timely recognition of systemic bacterial infections in pediatric care setting is
      the basis for effective treatment and control. This review provides an overview
      of procalcitonin (PCT) as an early marker for the detection of severe, invasive
      bacterial infection in children. Almost all articles on biochemical property and
      clinical studies in PubMed and Scopus databases regarding their use in pediatric
      infections and the use of PCT as a marker of bacterial infections were examined.
      Various methods and analyzers are currently available for the evaluation of PCT.
      Employment of PCT in the identification of neonatal bacterial infection is a
      complex process in some conditions. Age specific cut-off, underlying syndrome,
      and maternal antibiotics usage should be considered when PCT is to be applied in
      neonates. PCT might be false-negative in these conditions. However, if used
      appropriately, it can lead to a higher specificity than other immunologic
      markers. Due to its correlation with the severity of infection, PCT can
      consequently be used as a prognostic indicator especially for sepsis and urinary
      tract infection. It is, therefore, a practical supplementary means for the
      identification of bacterial infections in pediatric health settings.

PMID- 29203387
TI  - Alpinumisoflavone protects against glucocorticoid-induced osteoporosis through
      suppressing the apoptosis of osteoblastic and osteocytic cells.
AB  - The long-term use of glucocorticoids is found to cause osteoporosis. This study
      is designed to evaluate the protective effect of alpinumisoflavone (AIF), a
      naturally occurring flavonoid compound, on dexamethasone(Dex)-induced
      osteoporosis. We use a rat model to investigate the apoptosis of osteoblastic and
      osteocytic cells. The results indicate that AIF effectively protects against
      dexamethasone-induced osteoporosis. Moreover, AIF effectively reversed
      dexamethasone-induced apoptosis in osteoblastic and osteocytic cells through
      inhibiting ROS overproduction and regulating the Nrf2 pathway. In conclusion, the
      AIF activated Nrf2 signaling pathway was observed to suppress Dex-induced ROS
      production in osteoblastic and osteocytic cells, which may explain its anti
      osteoporotic effects against dexamethasone-induced osteoporosis.

PMID- 29203389
TI  - Leopoldina Symposium "Seasonal Rhythms", Leuven Belgium, 25. 8. 2016.

PMID- 29203388
TI  - The occurrence of intersex fishes in Boulder Creek, Colorado, is a recent
      phenomenon.
AB  - Gonads were examined visually and histologically from white sucker (Catostomus
      commersoni) and fathead minnows (Pimephales promelas) isolated from museum
      specimens collected from Boulder Creek, Colorado. These fishes were collected
      between 42 and 102 years ago before addition of large quantities of estrogenic
      chemicals via wastewater effluent was reported to disrupt reproductive structures
      and functions in white suckers living in Boulder Creek downstream of the
      wastewater treatment facility (WWTF) and in test exposures of fathead minnows to
      wastewater effluent at the WWTF. No evidence of abnormal external gonad
      appearance or histology (e.g., testicular oocytes, mixed gonadal tissue) were
      observed in male or female museum specimens of either species supporting the
      conclusion that observations of reproductive abnormalities, feminization,
      demasculinization, and altered sex ratios are recent phenomena.

PMID- 29203390
TI  - Ending the Global Tuberculosis Epidemic by 2030 - The Moscow Declaration and
      achieving a Major Translational Change in Delivery of TB Healthcare.

PMID- 29203391
TI  - Identification of a peptide derived from the heptad repeat 2 region of the
      porcine epidemic diarrhea virus (PEDV) spike glycoprotein that is capable of
      suppressing PEDV entry and inducing neutralizing antibodies.
AB  - Heptad repeat (HR) regions are highly conserved motifs located in the
      glycoproteins of enveloped viruses that form a six-helix bundle structure and is
      important in the process of virus fusion. Peptides derived from the HR regions of
      some viruses have also been shown to inhibit viral entry. Porcine epidemic
      diarrhea virus (PEDV) was predicted to have HR regions (HR1 and HR2) in the spike
      glycoprotein S2 subunit. Based on this analysis, six peptides derived from HR1
      and HR2 were selected, expressed in Escherichia coli, purified, and
      characterized. Three peptides (HR2M, HR2L and HR2P) were identified as potential
      competitive inhibitors in PEDV in vitro infection assays, with the HR2P peptide
      representing the most potent inhibitor. Further study indicated that immunization
      of HR2P in mice elicited antibodies capable of neutralizing PEDV infection in
      vitro. These results demonstrate that the HR2P peptide and anti-HR2P antibody can
      serve as a tool for dissecting the fusion mechanism of PEDV, guiding the search
      for potent inhibitors with therapeutic value against PEDV infection.

PMID- 29203392
TI  - Role of imaging-based biomarkers in NAFLD: Recent advances in clinical
      application and future research directions.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a major public health problem
      afflicting approximately one billion individuals worldwide. Liver biopsy is
      considered the gold standard for assessment of liver disease severity in patients
      with NAFLD. However, it is invasive, has high inter-observer variability, and is
      associated with adverse effects, including pain, infection and, albeit rarely,
      death. It is also impractical because of the large number of individuals who have
      NAFLD. Therefore, tools to non-invasively assess disease severity in NAFLD are
      urgently needed. Over the last two decades, tremendous advances have been made in
      the assessment of NAFLD by non-invasive imaging. In this review, we will discuss
      the different non-invasive imaging modalities available to quantify liver fat and
      liver fibrosis. We will also discuss the limitations of current modalities to
      detect the progressive form for NAFLD, termed non-alcoholic steatohepatitis.
      Finally, we will discuss the comparative efficacy of various imaging-based
      elastographic modalities for detection of advanced fibrosis or cirrhosis, as well
      as their diagnostic characteristics.

PMID- 29203395
TI  - Outcomes and Direct Costs of Inferior Vena Cava Filter Placement and Retrieval
      within the IR and Surgical Settings.
AB  - PURPOSE: To compare the outcomes and costs of inferior vena cava (IVC) filter
      placement and retrieval in the interventional radiology (IR) and surgical
      departments at a tertiary-care center. MATERIALS AND METHODS: Retrospective
      review was performed of 142 sequential outpatient IVC filter placements and 244
      retrievals performed in the IR suite and operating room (OR) from 2013 to 2016.
      Patient demographic data, procedural characteristics, outcomes, and direct costs
      were compared between cohorts. RESULTS: Technical success rates of 100% were
      achieved for both IR and OR filter placements, and 98% of filters were
      successfully retrieved by IR means, compared with 83% in the OR (P < .01).
      Fluoroscopy time was similar for IR and OR filter insertions, but IR retrievals
      required half the fluoroscopy time, with an average of 9 minutes vs 18 minutes in
      the OR (P = .02). There was no significant difference between cohorts in the
      incidences of complications for filter retrievals, but more postprocedural
      complications were observed for OR placements (8%) vs IR placements (1%; P =
      .05). The most severe complication occurred during an OR filter retrieval,
      resulting in entanglement of the snare device and conversion to an emergent open
      filter removal by vascular surgery. Direct costs were approximately 20% higher
      for OR vs IR IVC filter placements ($2,246 vs $2,671; P = .01). CONCLUSIONS:
      Filter placements are equally successfully performed in IR and OR settings, but
      OR patients experienced significantly higher postprocedural complication rates
      and incurred higher costs. In contrast, higher technical success rates and
      shorter fluoroscopy times were observed for IR filter retrievals compared with
      those performed in the OR.

PMID- 29203393
TI  - Pyrin Inflammasome Regulates Tight Junction Integrity to Restrict Colitis and
      Tumorigenesis.
AB  - BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) increase risk for colorectal
      cancer. Mutations in the Mediterranean fever gene (MEFV or pyrin) are associated
      with hereditary autoinflammatory disease and severe IBD. Expression of MEFV, a
      sensor protein that the initiates assembly of the inflammasome complex, is
      increased in colon biopsies from patients with IBD. We investigated the role of
      pyrin in intestinal homeostasis in mice. METHODS: Mefv-/- mice and C57/BL6 mice
      (controls) were given azoxymethane followed by multiple rounds of dextran sodium
      sulfate (DSS) to induce colitis and tumorigenesis. In some experiments, Mefv-/-
      mice were given injections of recombinant interleukin 18 (rIL18) or saline
      (control) during DSS administration. Colon tissues were collected at different
      time points during colitis development and analyzed by histology,
      immunohistochemistry, immunoblots, or ELISAs (to measure cytokines). Spleen and
      mesenteric lymph node were collected, processed, and analyzed by flow cytometry.
      Colon epithelial permeability was measured in mice with colitis by gavage of
      fluorescent dextran and quantification of serum levels. RESULTS: MEFV was
      expressed in colons of control mice and expression increased during chronic and
      acute inflammation; high levels were detected in colon tumor and adjacent non
      tumor tissues. Mefv-/- mice developed more severe colitis than control mice, with
      a greater extent of epithelial hyperplasia and a larger tumor burden. Levels of
      inflammatory cytokines (IL6) and chemokines were significantly higher in colons
      of Mefv-/- mice than control mice following colitis induction, whereas the level
      IL18, which depends on the inflammasome for maturation and release, was
      significantly lower in colons of Mefv-/- mice. Mefv-/- mice had increased
      epithelial permeability following administration of DSS than control mice, and
      loss of the tight junction proteins occludin and claudin-2 from intercellular
      junctions. STAT3 was activated (phosphorylated) in inflamed colon tissues from
      Mefv-/-, which also had increased expression of stem cell markers (OLFM4, BMI1,
      and MSI1) compared with colons from control mice. Administration of rIL18 to Mefv
      /- mice reduced epithelial permeability, intestinal inflammation, the severity of
      colitis, and colon tumorigenesis. CONCLUSIONS: In studies with DSS-induced
      colitis, we found that pyrin (MEFV) is required for inflammasome activation and
      IL18 maturation, which promote intestinal barrier integrity and prevent colon
      inflammation and tumorigenesis. Strategies to increase activity of MEFV or IL18
      might be developed for the treatment of IBD and prevention of colitis-associated
      tumorigenesis.

PMID- 29203394
TI  - Percutaneous Microwave versus Radiofrequency Ablation of Colorectal Liver
      Metastases: Ablation with Clear Margins (A0) Provides the Best Local Tumor
      Control.
AB  - PURPOSE: To identify and compare predictors of local tumor progression (LTP)-free
      survival (LTPFS) after radiofrequency (RF) ablation and microwave (MW) ablation
      of colorectal liver metastases (CLMs). MATERIALS AND METHODS: This is a
      retrospective review of CLMs ablated from November 2009 to April 2015 (110
      patients). Margins were measured on contrast-enhanced computed tomography (CT) 6
      weeks after ablation. Clinical and technical predictors of LTPFS were assessed
      using a competing risk model adjusted for clustering. RESULTS: Technique
      effectiveness (complete ablation) was 93% (79/85) for RF ablation and 97% (58/60)
      for MW ablation (P = .47). The median follow-up period was significantly longer
      for RF ablation than for MW ablation (56 months vs. 29 months) (P < .001). There
      was no difference in the local tumor progression (LTP) rates between RF ablation
      and MW ablation (P = 0.84). Significant predictors of shorter LTPFS for RF
      ablation on univariate analysis were ablation margins 5 mm or smaller (P < .001)
      (hazard ratio [HR]: 14.6; 95% confidence interval [CI]: 5.2-40.9) and
      perivascular tumors (P = .021) (HR: 2.2; 95% CI: 1.1-4.3); both retained
      significance on multivariate analysis. Significant predictors of shorter LTPFS on
      univariate analysis for MW ablation were ablation margins 5 mm or smaller (P <
      .001) (subhazard ratio: 11.6; 95% CI: 3.1-42.7) and no history of prior liver
      resection (P < .013) (HR: 3.2; 95%: 1.3-7.8); both retained significance on
      multivariate analysis. There was no LTP for tumors ablated with margins over 10
      mm (median LTPFS: not reached). Perivascular tumors were not predictive for MW
      ablation (P = .43). CONCLUSIONS: Regardless of the thermal ablation modality
      used, margins larger than 5 mm are critical for local tumor control, with no LTP
      noted for margins over 10 mm. Unlike RF ablation, the efficiency of MW ablation
      was not affected for perivascular tumors.

PMID- 29203396
TI  - [Exclusive salpingectomy or prophylactic salpingo-oophorectomy? Critical analysis
      of the latest French guidelines].

PMID- 29203397
TI  - Pro-arrhythmic effects of low plasma [K+] in human ventricle: An illustrated
      review.
AB  - Potassium levels in the plasma, [K+]o, are regulated precisely under
      physiological conditions. However, increases (from approx. 4.5 to 8.0mM) can
      occur as a consequence of, e.g., endurance exercise, ischemic insult or kidney
      failure. This hyperkalemic modulation of ventricular electrophysiology has been
      studied extensively. Hypokalemia is also common. It can occur in response to
      diuretic therapy, following renal dialysis, or during recovery from endurance
      exercise. In the human ventricle, clinical hypokalemia (e.g., [K+]o levels of
      approx. 3.0mM) can cause marked changes in both the resting potential and the
      action potential waveform, and these may promote arrhythmias. Here, we provide
      essential background information concerning the main K+-sensitive ion channel
      mechanisms that act in concert to produce prominent short-term ventricular
      electrophysiological changes, and illustrate these by implementing recent
      mathematical models of the human ventricular action potential. Even small changes
      (~1mM) in [K+]o result in significant alterations in two different K+ currents,
      IK1 and HERG. These changes can markedly alter in resting membrane potential
      and/or action potential waveform in human ventricle. Specifically, a reduction in
      net outward transmembrane K+ currents (repolarization reserve) and an increased
      substrate input resistance contribute to electrophysiological instability during
      the plateau of the action potential and may promote pro-arrhythmic early after
      depolarizations (EADs). Translational settings where these insights apply
      include: optimal diuretic therapy, and the interpretation of data from Phase II
      and III trials for anti-arrhythmic drug candidates.

PMID- 29203398
TI  - Metyrapone prevents acute glucose hypermetabolism and short-term brain damage
      induced by intrahippocampal administration of 4-aminopyridine in rats.
AB  - Intracerebral administration of the potassium channel blocker 4-aminopyridine (4
      AP) triggers neuronal depolarization and intense acute seizure activity followed
      by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat
      model of status epilepticus (SE), a single administration of metyrapone, an
      inhibitor of the 11beta-hydroxylase enzyme, had protective properties of
      preventive nature against signs of brain damage and neuroinflammation. Herein,
      our aim was to investigate to which extent, pretreatment with metyrapone (150
      mg/kg, i.p.) was also able to prevent eventual changes in the acute brain
      metabolism and short-term neuronal damage induced by intrahippocampal injection
      of 4-AP (7 MUg/5 MUl). To this end, regional brain metabolism was assessed by 2
      deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET)
      during the ictal period. Three days later, markers of neuronal death and
      hippocampal integrity and apoptosis (Nissl staining, NeuN and active caspase-3
      immunohistochemistry), neurodegeneration (Fluoro-Jade C labeling), astrogliosis
      (glial fibrillary acidic protein (GFAP) immunohistochemistry) and microglia
      mediated neuroinflammation (in vitro [18F]GE180 autoradiography) were evaluated.
      4-AP administration acutely triggered marked brain hypermetabolism within and
      around the site of injection as well as short-term signs of brain damage and
      inflammation. Most important, metyrapone pretreatment was able to reduce ictal
      hypermetabolism as well as all the markers of brain damage except microglia
      mediated neuroinflammation. Overall, our study corroborates the neuroprotective
      effects of metyrapone against multiple signs of brain damage caused by seizures
      triggered by 4-AP. Ultimately, our data add up to the consistent protective
      effect of metyrapone pretreatment reported in other models of neurological
      disorders of different etiology.

PMID- 29203399
TI  - Anti-thyroid antibodies and thyroid function in anti-N-methyl-d-aspartate
      receptor encephalitis.

PMID- 29203401
TI  - Skeletal muscle from aged American Quarter Horses shows impairments in
      mitochondrial biogenesis and expression of autophagy markers.
AB  - Aging is associated with decreased mitochondrial content and function in skeletal
      muscle, possibly due to compromised biogenesis and autophagic removal of
      dysfunctional mitochondria. The aim of this study was to compare markers of
      mitochondrial content and biogenesis and of autophagy between skeletal muscle
      from young and aged American Quarter Horses. Citrate synthase protein and mtDNA
      copy number were decreased in triceps brachii (TB) muscle (P<0.05) from aged
      horses, suggesting an age-related decline in mitochondrial content.
      Concomitantly, mRNA expression of PGC-1alpha and TFAM, regulators of
      mitochondrial biogenesis, was lower in aged compared to young TB (P<0.05).
      Expression of autophagy markers suggested an age-associated decline of autophagy.
      The autophagosomal cargo protein SQSTM/p62 accumulated with age in both muscles
      (P<0.05). Expression of Autophagy-related protein Atg5 (P<0.05) and the
      autophagosome-bound form of Microtubule-associated protein light chain 3 (LC3-II;
      P<0.05) were lower in aged compared to young TB. While LC3 transcript level was
      elevated in aged compared to young GM (P<0.001), protein expression of LC3-II was
      unaffected. Gene expression of Lysosomal Membrane-Associated Protein 2 (LAMP2)
      was not affected by age in either muscle. However, LAMP2 protein expression
      declined with age (P<0.05), suggesting a decline in autophagosome-lysosome
      fusion. Taken together, our data indicate that equine skeletal muscle
      mitochondrial content and biogenesis were impaired with age. Further,
      autophagosome formation and lysosomal degradation were negatively affected in
      aged TB and GM, respectively. Future research needs to explore whether
      interventions targeting these cellular processes can prolong health and
      performance of aging American Quarter Horses.

PMID- 29203400
TI  - Decreased NLRP3 inflammasome expression in aged lung may contribute to increased
      susceptibility to secondary Streptococcus pneumoniae infection.
AB  - Post-viral pneumococcal pneumonia is a leading morbidity and mortality in older
      patients (>=65years of age). The goal of our current study is to understand the
      impact of chronological aging on innate immune responses to a secondary, post
      viral infection with Streptococcus pneumoniae, a causative agent of bacterial
      pneumonia. Using aged murine models of infection, our findings demonstrate
      increased morbidity and mortality in aged mice within 48h post-secondary S.
      pneumoniae infection. Increased susceptibility of aged mice was associated with
      decreased TLR1, TLR6, and TLR9 mRNA expression and diminished IL1beta mRNA
      expression. Examination of NLRP3 inflammasome expression illustrated decreased
      NLRP3 mRNA expression and decreased IL1beta production in aged lung in response
      to secondary S. pneumoniae infection.

PMID- 29203402
TI  - Lamin A expression in circulating osteoprogenitors as a potential biomarker for
      frailty: The Nepean Osteoporosis and Frailty (NOF) Study.
AB  - Lamin A is a protein of the nuclear lamina. Low levels of lamin A expression are
      associated with osteosarcopenia in mice. In this study, we hypothesized that low
      lamin A expression is also associated with frailty in humans. We aimed to develop
      a non-invasive method to quantify lamin A expression in epithelial and
      circulating osteoprogenitor (COP) cells, and to determine the relationship
      between lamin A expression and frailty in older individuals. COP cells and buccal
      swabs were obtained from 66 subjects (median age 74; 60% female; 26 non-frail, 23
      pre-frail, and 17 frail) participating at the Nepean Osteoporosis and Frailty
      (NOF) Study. We quantified physical performance and disability, and stratified
      frailty in this population. Lamin A expression in epithelial and COP cells was
      quantified by flow cytometry. Linear regression models estimated the relationship
      between lamin A expression in buccal and COP cells, and prevalent disability and
      frailty. Lamin A expression in buccal cells showed no association with either
      disability or frailty. Low lamin A expression values in COP cells were associated
      with frailty. Frail individuals showed 60% lower levels of lamin A compared to
      non-frail (95% CI -36 to -74%, p<0.001) and 62% lower levels compared to pre
      frail (95%CI -40 to -76%, p<0.001). In summary, we have identified lamin A
      expression in COP cells as a strong indicator of frailty. Further work is needed
      to understand lamin A expression as a risk stratifier, biomarker, or therapeutic
      target in frail older persons.

PMID- 29203403
TI  - Carcinogenicity assessment of baricitinib in Tg.rasH2 mice and Sprague-Dawley
      (Crl:CD) rats.
AB  - Baricitinib is a potent and selective Janus kinase (JAK)1 and JAK2 inhibitor, and
      is approved for the treatment of moderately to severely active RA in adults in
      Europe, Japan, and other countries. This study evaluated the carcinogenic
      potential of baricitinib in Tg. rasH2 mice and Sprague-Dawley (Crl:CD) rats.
      Baricitinib was administered daily by oral gavage to Crl:CD rats for up to 94
      weeks (dose levels of 0, 1, 3, or 8 mg/kg for males and 0, 3, 8, or 25 mg/kg for
      females) and to Tg. rasH2 mice for 26 weeks (dose levels of 0, 15, 40, or 300
      mg/kg for males and 0, 10, 30, or 150 mg/kg for females). Baricitinib was well
      tolerated with no incidence of compound-related neoplasms at any dose levels in
      rats and mice. In mice, non-neoplastic events observed were bone marrow
      hypocellularity and increased adipocytes. In rats, baricitinib administration was
      associated with a dose-dependent increase in survival, with a decreased incidence
      of neoplasm (hematopoietic and mammary), potentially secondary to drug-related
      decreased weight gain. The incidence of proliferative changes such as neoplastic
      and hyperplastic lesions in the mammary glands of females and in the livers of
      males and females also decreased. In conclusion, baricitinib is not considered to
      be carcinogenic.

PMID- 29203404
TI  - The imaging FCS diffusion law in the presence of multiple diffusive modes.
AB  - The cellular plasma membrane is the barrier over which cells exchange materials
      and communicate with their surroundings, and thus plays the central role in
      cellular sensing and metabolism. Therefore, the investigation of plasma membrane
      organization and dynamics is required for understanding of cellular functions.
      The plasma membrane is a heterogeneous matrix. The presence of structures such as
      lipid and protein domains and the cytoskeleton meshwork poses a hindrance to the
      free diffusion of membrane associated biomolecules. However, these domains and
      the cytoskeleton meshwork barriers are below the optical diffraction limit with
      potentially short lifetimes and are not easily detected even in super-resolution
      microscopy. Therefore, dynamic measurements are often used to indirectly prove
      the existence of domains and barriers by analyzing the mode of diffusion of probe
      molecules. One of these tools is the Fluorescence Correlation Spectroscopy (FCS)
      diffusion law. The FCS diffusion law is a plot of diffusion time (taud) versus
      observation area. For at least three different diffusive modes - free, domain
      confined, and meshwork hindered hop diffusion - the expected plots have been
      characterized, typically by its y-intercept (tau0) when fit with a linear model,
      and have been verified in many cases. However, a description of tau0 has only
      been given for pure diffusive modes. But in many experimental cases it is not
      evident that a protein will undergo only one kind of diffusion, and thus the
      interpretation of the tau0 value is problematic. Here, we therefore address the
      question about the absolute value of tau0 in the case of complex diffusive modes,
      i.e. when either one molecule is domain confined and cytoskeleton hindered or
      when two molecules exhibit different diffusive behavior at the same position in a
      sample. In addition, we investigate how tau0 changes when the diffusive mode of a
      probe alters upon disruption of domains or the cytoskeleton by drug treatments.
      By a combination of experimental studies and simulations, we show that tau0 is
      not influenced equally by the different diffusive modes as typically found in
      cellular environments, and that it is the relative change of tau0 rather than its
      absolute value that provides information on the mode of diffusion.

PMID- 29203405
TI  - Inactivation of the arn operon and loss of aminoarabinose on lipopolysaccharide
      as the cause of susceptibility to colistin in an atypical clinical isolate of
      proteus vulgaris.
AB  - Colistin has become a last-line antibiotic for the treatment of multidrug
      resistant bacterial infections; however, resistance to colistin has emerged in
      recent years. Some bacteria, such as Proteus and Serratia spp., are intrinsically
      resistant to colistin although the exact mechanism of resistance is unknown. Here
      we identified the molecular support for intrinsic colistin resistance in Proteus
      spp. by comparative genomic, transcriptomic and proteomic analyses of colistin
      susceptible (CSUR P1868_S) and colistin-resistant (CSUR P1867_R) strains of an
      atypical Proteus vulgaris. A significant difference in outer membrane glycoside
      structures in both strains that was corroborated by MALDI-TOF/MS analysis was
      found, which showed an absence of 4-amino-4-deoxy-l-arabinose (L-Ara4N) in the
      outer membrane lipid A moiety of the susceptible strain. Comparative genomic
      analysis with other resistant strains of P. vulgaris available in a local
      database found a mutation in the arnBCADTEF operon of the susceptible strain.
      Transcriptomic analysis of genes belonging to the arnBCADTEF operon showed a
      significant decrease in mRNA expression level of these genes in the susceptible
      strain, supporting addition of L-Ara4N in the outer membrane lipid A moiety as an
      explanation for colistin resistance. Insertion of the arnD gene that was
      suggested to be altered in the susceptible strain by in silico analysis led to a
      16-fold increase of colistin MIC in the susceptible strain, confirming its role
      in colistin resistance in this species. Here we show that constitutive activation
      of the arn operon and addition of L-Ara4N is the main molecular mechanism of
      colistin resistance in P. vulgaris.

PMID- 29203406
TI  - Acid and nonacid gastroesophageal reflux after single anastomosis gastric bypass.
      An objective assessment using 24-hour multichannel intraluminal impedance-pH
      metry.
AB  - BACKGROUND: Single anastomosis gastric bypass (SaGB) was introduced in 2001 as an
      alternative to "loop" gastric bypass. It was considered as a procedure that would
      eliminate alkaline reflux and associated esophagitis. OBJECTIVES: Existing
      evidence about the postoperative incidence of gastroesophageal reflux (GERD)
      after SaGB is based on studies using symptom questionnaires. The aim of our study
      was to evaluate GERD 12 months after SaGB by using 24-hour multichannel
      intraluminal impedance pH metry (24-h MIIpH). SETTING: Surgical department of a
      university hospital METHODS: Morbidly obese candidates for SaGB underwent 24-hour
      MIIpH prior and 12 months after their bariatric procedure. RESULTS: There were 11
      patients included in this prospective study. Results of 24-hour MIIpH revealed
      that DeMeester score (40.48 versus 24.16, P = .339) had an increasing trend 12
      months after SaGB. Acid reflux episodes decreased, whereas nonacid reflux
      episodes increased postoperatively, both in proximal and distal esophagus. Total
      median bolus clearance time and acid clearance time increased. De novo GERD
      developed in 2 patients (28.6%) and worsening of already existing GERD developed
      in all patients with preoperative evidence of GERD. CONCLUSION: The use of
      symptom questionnaires to assess postoperative GERD after SaGB may not accurately
      depict the real image. Twenty-four-hour MIIpH in 12 months after SaGB revealed an
      increase of total number of nonacid reflux episodes and a decrease of total
      number of acid reflux episodes, with longer duration of each acid reflux episode.
      Close postoperative follow-up with reflux testing and possibly endoscopy could
      eliminate the risk of complicated GERD.

PMID- 29203407
TI  - Optimising workflow processes in an advanced medication dispensary.
AB  - The workload measurement of an inpatient hospital dispensary is critical to
      improve efficiency in the face of limited budgets. This single-centre pilot study
      used work sampling to observe and identify areas to improve efficiency of
      dispensing prescribed medications at one tertiary level acute care teaching
      hospital. Workload sampling was conducted at a 1096-bed hospital in Calgary,
      Alberta, Canada. The dispensary services the entire hospital, 24 h per day, seven
      days per week. Pharmacists are solely involved in clinical screening. The
      hospital uses a tech-check-tech practice. The observer was a registered
      pharmacist who collected data in the dispensary over two-hour blocks during
      November 14-24, 2017. A pre-made data collection sheet was used to record
      observations. Pharmacists duplicated tasks performed by dispensary technicians,
      such as ensuring STAT orders were delivered or identifying floor stock
      medications. Assistants inconsistently organised orders for filling. The
      assistant delivering STAT medications was difficult to find. Not all STAT
      medications were delivered first on a scheduled delivery route. Overall, areas
      for improvement in the dispensary process may include reinforcing the pharmacist
      clinical duties, establishing clinical competency baseline, supporting the full
      scope of practice of registered technicians, and consistent training of
      assistants, and clarifying communication processes.

PMID- 29203408
TI  - Medication non-adherence and uncertainty: Information-seeking and processing in
      the Danish LIFESTAT survey.
AB  - BACKGROUND: Statins are widely prescribed to lower cardiovascular morbidity and
      mortality. However, statin non-adherence is very high. PURPOSE: The aim of this
      paper was to investigate reasons for stopping statin treatment in the general
      population and to study how aspects of information-seeking and processing is
      associated with statin non-adherence. METHODS: This study used a population
      survey on 3050 Danish residents aged 45-65 years. Reasons for statin
      discontinuation was studied among those who were previous statin users. The
      association between information seeking and processing and statin discontinuation
      were analysed using multivariate logistical regression models. RESULTS:
      Experience of side effects and fear of side effects played an important role in
      the discontinuation of statin treatment. Feelings of uncertainty and confusion
      regarding information on statins predicted statin discontinuation. This applied
      to information from both mass media and from general practitioners. There was no
      clear pattern of information seeking and statin non-adherence. CONCLUSIONS: The
      article point to the impact of information-seeking on the decision to take
      cholesterol-lowering medication. This included contributions from information
      disseminated by media outlets. Side effects and fear of side effects should be
      addressed in clinical practice. Health care professionals should pay attention to
      emotional aspects of how information is disseminated and perceived by statin
      users.

PMID- 29203409
TI  - Nanoelectronics enabled chronic multimodal neural platform in a mouse ischemic
      model.
AB  - BACKGROUND: Despite significant advancements of optical imaging techniques for
      mapping hemodynamics in small animal models, it remains challenging to combine
      imaging with spatially resolved electrical recording of individual neurons
      especially for longitudinal studies. This is largely due to the strong
      invasiveness to the living brain from the penetrating electrodes and their
      limited compatibility with longitudinal imaging. NEW METHOD: We implant arrays of
      ultraflexible nanoelectronic threads (NETs) in mice for neural recording both at
      the brain surface and intracortically, which maintain great tissue compatibility
      chronically. By mounting a cranial window atop of the NET arrays that allows for
      chronic optical access, we establish a multimodal platform that combines
      spatially resolved electrical recording of neural activity and laser speckle
      contrast imaging (LSCI) of cerebral blood flow (CBF) for longitudinal studies.
      RESULTS: We induce peri-infarct depolarizations (PIDs) by targeted
      photothrombosis, and show the ability to detect its occurrence and propagation
      through spatiotemporal variations in both extracellular potentials and CBF. We
      also demonstrate chronic tracking of single-unit neural activity and CBF over
      days after photothrombosis, from which we observe reperfusion and increased
      firing rates. COMPARISON WITH EXISTING METHOD(S): This multimodal platform
      enables simultaneous mapping of neural activity and hemodynamic parameters at the
      microscale for quantitative, longitudinal comparisons with minimal perturbation
      to the baseline neurophysiology. CONCLUSION: The ability to spatiotemporally
      resolve and chronically track CBF and neural electrical activity in the same
      living brain region has broad applications for studying the interplay between
      neural and hemodynamic responses in health and in cerebrovascular and
      neurological pathologies.

PMID- 29203410
TI  - Breathing disturbances in a model of Rett syndrome: A potential involvement of
      the glycine receptor alpha3 subunit?
AB  - The glycine receptor alpha3 subunit is known to be a target for cAMP/PKA-mediated
      phosphorylation and regulation. Mice that lack this subunit are apparently normal
      but the 5-HT1A-receptor mediated modulation of respiratory network activity is
      disturbed. Since the intracellular cAMP-concentration is reduced in mice that
      lack the transcriptional modulator methyl-CpG-binding protein 2 (MeCP2) gene, we
      aimed to test if the alpha3 subunit of the glycine receptor is involved in the
      development of the breathing phenotype of MeCP2-deficient mice (Mecp2-/y).
      Therefore, we generated a double knock-out mouse line that lacks both the Mecp2
      gene as well as the gene (Glra3) for the alpha3 subunit of the ionotropic glycine
      receptor. As compared to WT and Glra3-/- mice, both Mecp2-/y mice and Mecp2-/y;
      Glra3-/- mice (DKO) showed a slower respiratory rate and a tendency towards
      higher numbers of apneas. Interestingly, the irregularity of the breathing was
      significantly reduced in DKO as compared to Mecp2-/y littermates. In the light of
      the unaltered survival of DKO mice, however, the contribution of the glycine
      receptor alpha3 subunit for development and progression of the breathing
      disturbances in the mouse model of Rett syndrome appears to be only of minor
      relevance.

PMID- 29203411
TI  - Controlled-shed poultry farming practices in Pakistan select for antibiotic
      resistant Escherichia coli.

PMID- 29203412
TI  - Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic
      Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia.
AB  - Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic
      hematopoietic cell transplantation (HCT) for cure. With the evolution of
      conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have
      improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD
      HCT; n = 17) and AD-HCT (n = 57) performed for FA-associated SAA at a single
      institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD
      HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet
      recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD)
      was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was
      0 versus 7%, with no statistically significant differences by type of transplant.
      The use of UCB was associated with decreased rates of neutrophil recovery in AD
      HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher
      serious infection density before day +100 post-HCT was observed in AD-HCT
      compared with MSD-HCT (P = .02). These data demonstrate that AD-HCT should be
      considered at the same time as MSD-HCT for patients with FA-associated SAA.

PMID- 29203413
TI  - Targeted Magnetic Intra-Lysosomal Hyperthermia produces lysosomal reactive oxygen
      species and causes Caspase-1 dependent cell death.
AB  - Therapeutic strategies using drugs which cause Lysosomal Cell Death have been
      proposed for eradication of resistant cancer cells. In this context, nanotherapy
      based on Magnetic Intra-Lysosomal Hyperthermia (MILH) generated by magnetic
      nanoparticles (MNPs) that are grafted with ligands of receptors overexpressed in
      tumors appears to be a very promising therapeutic option. However, mechanisms
      whereby MILH induces cell death are still elusive. Herein, using Gastrin-grafted
      MNPs specifically delivered to lysosomes of tumor cells from different cancers,
      we provide evidences that MILH causes cell death through a non-apoptotic
      signaling pathway. The mechanism of cell death involves a local temperature
      elevation at the nanoparticle periphery which enhances the production of reactive
      oxygen species through the lysosomal Fenton reaction. Subsequently, MILH induces
      lipid peroxidation, lysosomal membrane permeabilization and leakage of lysosomal
      enzymes into the cytosol, including Cathepsin-B which activates Caspase-1 but not
      apoptotic Caspase-3. These data highlight the clear potential of MILH for the
      eradication of tumors overexpressing receptors.

PMID- 29203414
TI  - Complement activation in vitro and reactogenicity of low-molecular weight dextran
      coated SPIONs in the pig CARPA model: Correlation with physicochemical features
      and clinical information.
AB  - The unique magnetic properties of superparamagnetic iron oxide nanoparticles
      (SPIONs) have led to their increasing use in drug delivery and imaging
      applications. Some polymer-coated SPIONs, however, share with many other
      nanoparticles the potential of causing hypersensitivity reactions (HSRs) known as
      complement (C) activation-related pseudoallergy (CARPA). In order to explore the
      roles of iron core composition and particle surface coating in SPION-induced
      CARPA, we measured C activation by 6 different SPIONs in a human serum that is
      known to react to nanoparticles (NPs) with strong C activation. Remarkably, only
      the carboxymethyldextran-coated (ferucarbotran, Resosvist(r)) and dextran-coated
      (ferumoxtran-10, Sinerem(r)) SPIONs caused significant C activation, while the
      citric acid, phosphatidylcholine, starch and chitosan-coated SPIONs had no such
      effect. Focusing on Resovist and Sinerem, we found Sinerem to be a stronger
      activator of C than Resovist, although the individual variation in 15 different
      human sera was substantial. Further analysis of C activation by Sinerem indicated
      biphasic dose dependence and significant production of C split product Bb but not
      C4d, attesting to alternative pathway C activation only at low doses. Consistent
      with the strong C activation by Sinerem and previous reports of HSRs in man,
      injection of Sinerem in a pig led to dose-dependent CARPA, while Resovist was
      reaction-free. Using nanoparticle tracking analysis, it was further determined
      that Sinerem, more than Resovist, displayed multimodal size distribution and
      significant fraction of aggregates - factors which are known to promote C
      activation and CARPA. Taken together, our findings offer physicochemical insight
      into how key compositional factors and nanoparticle size distribution affect
      SPION-induced CARPA, a knowledge that could lead to the development of SPIONs
      with improved safety profiles.

PMID- 29203415
TI  - Microneedles as the technique of drug delivery enhancement in diverse organs and
      tissues.
AB  - Microneedles is the technique of drug delivery enhancement, which was primarily
      designed for facilitating percutaneous drug delivery. Started from the
      development of simple solid microneedles, providing microporation of stratum
      corneum and therefore enhancement of topical drug delivery, for two decades the
      technique has progressed in various modifications such as hollow, coated,
      dissolving and hydrogel forming microneedles. In their turn, the modifications
      have resulted in new mechanisms of drug delivery enhancement and followed by the
      expansion of applicability range in terms of targeted tissues and organs. Thus,
      in addition to percutaneous drug delivery, microneedles have been considered as
      an efficient technique facilitating ocular, oral mucosal, gastrointestinal,
      ungual and vaginal drug administration. It is anticipated that the technique of
      microneedle-assisted drug delivery will soon become relevant for majority of
      organs and tissues.

PMID- 29203416
TI  - Quantitative contributions of processes by which polyanion drugs reduce
      intracellular bioavailability and transfection efficiency of cationic siRNA
      lipoplex.
AB  - RNA Interference (RNAi) is a potentially useful tool to correct the detrimental
      effects of faulty genes; several RNAi are undergoing clinical evaluation in
      various diseases. The present study identified the relative contributions of
      three mechanisms by which polyanion drugs reduced the gene silencing activity of
      Lipoplex, a complex of small interfering RNA (siRNA) and cationic liposomes. The
      study used a siRNA against the chemoresistance gene survivin and two model
      polyanion drugs (suramin, heparin). Products of Lipoplex destabilization were
      separated, identified, and/or quantified using ultrafiltration, gel
      electrophoresis, and RT-qPCR (quantitative reverse transcription polymerase chain
      reaction). Cell binding and endocytosis of fluorescence-labeled Lipoplex and the
      amount of siRNA at its site of action RISC (RNA-induced silencing complex) were
      evaluated using endocytosis markers, confocal microscopy, quantitative image
      analysis, immunoprecipitation, and RT-qPCR. The results show suramin and heparin
      exerted multiple concentration-dependent effects. First, these agents altered
      several Lipoplex properties (i.e., reduced particle size, changed surface charge,
      modified composition of protein biocorona). Second, both caused Lipoplex
      destabilization to release double- and single-strand siRNA and/or smaller siRNA
      lipid complexes with reduced siRNA cargo. Third, both prevented the cell surface
      binding and internalization of Lipoplex, diminished the siRNA concentration in
      RISC, and retarded the mRNA knockdown. Suramin and heparin yielded qualitatively
      and quantitatively different results. Analysis of the experimental results of
      suramin using quantitative pharmacology (QP) modeling indicated the major cause
      of gene silencing activity loss depended on drug concentration, changing from
      inhibition of endocytosis at lower concentration (accounting for 60% loss at
      ~9MUM) to inhibition of cell surface binding and loss of siRNA cargo at higher
      concentrations (accounting for 64% and 27%, respectively, at 70MUM). In summary,
      the present study demonstrates the complex and dynamic interactions between
      polyanions and Lipoplex, and the use of QP modeling to delineate the
      contributions of three mechanisms to the eventual loss of gene silencing
      activity.

PMID- 29203417
TI  - Phase behavior in the biologically important oleic acid/sodium oleate/water
      system.
AB  - The phase behavior in the oleic acid/sodium oleate/normal saline (0.15M NaCl
      aqueous solution) system has been determined. For this purpose visual inspection
      of samples between crossed polarizers, and Small Angle X-ray diffraction was used
      to identify the various phases and their unit cell dimensions. A rich phase
      behavior was observed for the ternary system, featuring reverse micellar,
      micellar cubic, hexagonal, and cubic phases, and large regions with lamellar
      phases. As expected the ratio the 'oleic acid/sodium oleate' determines the pH
      and as a consequence the phase behavior. The results could be modeled by an
      extended Henderson-Hasselbalch (HH) equation, which takes into account the
      electrostatic potential at the aqueous lipid interface. The knowledge obtained is
      important for understanding the lipolysis of triglycerides, as the phase behavior
      of the end-product of the reaction regulates how well the insoluble product can
      be dispersed and consequently the kinetics of the process.

PMID- 29203418
TI  - Electronic medical records can be used to emulate target trials of sustained
      treatment strategies.
AB  - OBJECTIVE: To emulate three target trials: single treatment vs. no treatment,
      joint treatment vs. no treatment, and head-to-head comparison of two treatments,
      we explain how to estimate the observational analogs of intention-to-treat and
      per-protocol effects, using hazard ratios and survival curves. For per-protocol
      effects, we describe two methods for adherence adjustment via inverse-probability
      weighting. STUDY DESIGN AND SETTING: Prospective observational study using
      electronic medical records of individuals aged 55-84 with coronary heart disease
      from >500 practices in the United Kingdom between 2000 and 2010. RESULTS: The
      intention-to-treat mortality hazard ratio (95% confidence interval) was 0.90
      (0.84, 0.97) for statins vs. no treatment, 0.88 (0.73, 1.06) for statins plus
      antihypertensives vs. no treatment, and 0.91 (0.77, 1.06) for atorvastatin vs.
      simvastatin. When censoring nonadherent person-times, the per-protocol mortality
      hazard ratio was 0.74 (0.64, 0.85) for statins vs. no treatment, 0.55 (0.35,
      0.87) for statins plus antihypertensives vs. no treatment, and 1.13 (0.88, 1.45)
      for atorvastatin vs. simvastatin. We estimated per-protocol hazard ratios for a 5
      year treatment using different dose-response marginal structural models and
      standardized survival curves for each target trial using intention-to-treat and
      per-protocol analyses. CONCLUSION: When randomized trials are not available or
      feasible, observational analyses can emulate a variety of target trials.

PMID- 29203419
TI  - Flaws in the application and interpretation of statistical analyses in systematic
      reviews of therapeutic interventions were common: a cross-sectional analysis.
AB  - OBJECTIVES: The objective of the study was to investigate the application and
      interpretation of statistical analyses in a cross-section of systematic reviews
      (SRs) of therapeutic interventions, without restriction by journal, clinical
      condition, or specialty. STUDY DESIGN AND SETTING: We evaluated a random sample
      of SRs assembled previously, which were indexed in MEDLINE(r) during February
      2014, focused on a treatment or prevention question, and reported at least one
      meta-analysis. The reported statistical methods used in each SR were extracted
      from articles and online appendices by one author, with a 20% random sample
      extracted in duplicate. RESULTS: We evaluated 110 SRs; 78/110 (71%) were non
      Cochrane SRs and 55/110 (50%) investigated a pharmacological intervention. The
      SRs presented a median of 13 (interquartile range: 5-27) meta-analytic effects.
      When considering the index (primary or first reported) meta-analysis of each SR,
      just over half (62/110 [56%]) used the random-effects model, but few (5/62 [8%])
      interpreted the meta-analytic effect correctly (as the average of the
      intervention effects across all studies). A statistical test for funnel plot
      asymmetry was reported in 17/110 (15%) SRs; however, in only 4/17 (24%) did the
      test include the recommended number of at least 10 studies of varying size.
      Subgroup analyses accompanied 42/110 (38%) index meta-analyses, but findings were
      not interpreted with respect to a test for interaction in 29/42 (69%) cases, and
      the issue of potential confounding in the subgroup analyses was not raised in any
      SR. CONCLUSIONS: There is scope for improvement in the application and
      interpretation of statistical analyses in SRs of therapeutic interventions. The
      involvement of statisticians on the SR team and establishment of partnerships
      between researchers with specialist expertise in SR methods and journal editors
      may help overcome these shortcomings.

PMID- 29203420
TI  - Compound action potential inhibition produced by various antidepressants in the
      frog sciatic nerve.
AB  - Although an inhibition of action potential conduction in nerve fibers possibly
      contributes to at least a part of antinociception produced by analgesics and the
      adjuvants, it has not been fully examined yet how the conduction inhibition
      differs in extent among their drugs. We investigated the effects of various
      antidepressants used as analgesic adjuvants on compound action potentials (CAPs)
      recorded from the frog sciatic nerve by using the air-gap method. The results
      were compared with those of the other adjuvants that were reported previously.
      Antidepressants, duloxetine (serotonin and noradrenaline reuptake inhibitor,
      SNRI), fluoxetine (selective serotonin reuptake inhibitor, SSRI), amitriptyline
      (tricyclic tertiary amine), desipramine (tricyclic secondary amine) and
      maprotiline (tetracyclic secondary amine), reduced the peak amplitude of the CAP
      with half-maximal inhibitory concentration (IC50) values of 0.23, 1.5, 0.26, 1.6
      and 0.95mM, respectively. Trazodone (non-SNRI, -SSRI, -tricyclic and -tetracyclic
      antidepressant) at 1.0mM reduced CAP amplitude by about 50%. The duloxetine and
      amitriptyline values were comparable to those of lamotrigine and carbamazepine
      (antiepileptics), dexmedetomidine (alpha2-adrenoceptor agonist) and ropivacaine,
      levobupivacaine and pramoxine (local anesthetics). The fluoxetine, desipramine,
      maprotiline and trazodone values were similar to those of oxymetazoline (alpha2
      adrenoceptor agonist) and lidocaine, cocaine, procaine and prilocaine (local
      anesthetics). The antidepressants' IC50 values were much larger than that of
      tetracaine (local anesthetic). In conclusion, the six antidepressants inhibited
      CAPs with efficacies comparable to some antiepileptics, alpha2-adrenoceptor
      agonists and local anesthetics. It was suggested that antidepressants inhibit
      nerve conduction with efficacies comparable to those of the other adjuvants.

PMID- 29203421
TI  - Executive function performance in obesity and overweight individuals: A meta
      analysis and review.
AB  - Prior research has suggested that obesity/overweight may be associated with
      deficits in executive function. If true, this has important clinical
      implications. In this review, we synthesize the current literature by conducting
      a meta-analysis of studies comparing executive functions in overweight/obese
      individuals to normal weight controls. We identified 72 studies-with 4904
      overweight/obese participants-that met our inclusion criteria. Effect sizes were
      analyzed using the robust variance estimation random effects meta-regression
      technique. It was found that obese participants showed broad impairments on
      executive function, including on tasks primarily utilizing inhibition, cognitive
      flexibility, working memory, decision-making, verbal fluency, and planning;
      overweight participants only showed significant deficits in inhibition and
      working memory. The only moderator of effects of obesity to emerge significant
      was the task used to assess the respective executive function, which moderated
      effects of obesity on working memory and decision-making. There were not enough
      studies of overweight individuals to make strong claims about moderating effects
      in those studies. In sum, current evidence supports the existence of broad
      executive function deficits in obese individuals, and inhibition and working
      memory deficits in overweight individuals.

PMID- 29203423
TI  - Compulsivity-related neurocognitive performance deficits in gambling disorder: A
      systematic review and meta-analysis.
AB  - Compulsivity is a core feature of addictive disorders, including gambling
      disorder. However, it is unclear to what extent this compulsive behavior in
      gambling disorder is associated with abnormal compulsivity-related neurocognitive
      functioning. Here, we summarize and synthesize the evidence for compulsive
      behavior, as assessed by compulsivity-related neurocognitive tasks, in
      individuals with gambling disorder compared to healthy controls (HCs). A total of
      29 studies, comprising 41 task-results, were included in the systematic review;
      32 datasets (n=1072 individuals with gambling disorder; n=1312 HCs) were also
      included in the meta-analyses, conducted for each cognitive task separately. Our
      meta-analyses indicate significant deficits in individuals with gambling disorder
      in cognitive flexibility, attentional set-shifting, and attentional bias.
      Overall, these findings support the idea that compulsivity-related performance
      deficits characterize gambling disorder. This association may provide a possible
      link between impairments in executive functions related to compulsive action. We
      discuss the practical relevance of these results, their implications for our
      understanding of gambling disorder and how they relate to neurobiological factors
      and other 'disorders of compulsivity'.

PMID- 29203424
TI  - Depression subtyping based on evolutionary psychiatry: From reactive short-term
      mood change to depression.

PMID- 29203422
TI  - Pavlovian conditioned diminution of the neurobehavioral response to threat.
AB  - An important function of emotion is that it motivates us to respond more
      effectively to threats in our environment. Accordingly, healthy emotional
      function depends on the ability to appropriately avoid, escape, or defend against
      threats we encounter. Thus, from a functional perspective, it is important to
      understand the emotional response to threat. However, prior work has largely
      focused on the emotional response in anticipation of threat, rather than the
      emotional response to the threat itself. The current review is focused on recent
      behavioral, psychophysiological, and neural findings from Pavlovian conditioning
      research that is centered on the expression and regulation of the emotional
      response to threat. The current evidence suggests that a neural network that
      includes the prefrontal cortex, hippocampus, and amygdala underlies learning,
      expression, and regulation processes that modulate emotional responses to threat.
      This line of research has important implications for our understanding of emotion
      regulation and stress resilience.

PMID- 29203425
TI  - TGFbeta1 transduction enhances immunomodulatory capacity of neural stem cells in
      experimental autoimmune encephalomyelitis.
AB  - Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE,
      an animal model of multiple sclerosis. However, the beneficial effect is
      suboptimal due to the limited immunomodulatory capacity of these cells. In this
      study, we engineered BM-NSCs with inducible TGFbeta1, a potent immunosuppressive
      cytokine, to enhance their anti-inflammatory capacity. We found that i.v.
      injected TGFbeta1-BM-NSCs more effectively suppressed clinical severity,
      inflammation and demyelination of the central nervous system of EAE mice.
      Transduction of TGFbeta1 resulted in a higher percentage of Tregs and lower
      percentage of Th1 and Th17 cells in the periphery, with increased production of
      IL-10, and reduced production of IFN-gamma, IL-17 and GM-CSF. Moreover, myelin
      specific splenic proliferation was also inhibited more profoundly by TGFbeta1-BM
      NSCs. We also found that TGFbeta1-BM-NSCs have the capacity to switch microglia
      from M1 to M2 phenotype. On the other hand, transduction of TGFbeta1 did not
      affect proliferative ability and differentiating potential of BM-NSCs in vitro
      and in vivo. Together, these findings demonstrate that transduction of TGFbeta1
      significantly enhanced the immunomodulatory capacity of BM-NSCs for EAE
      treatment, through inducing Tregs and an M2 phenotype of macrophages/microglia,
      while retaining their capacity for neural cell differentiation. Thus, our study
      provides an easily accessible, inducible and effective therapy for CNS
      inflammatory demyelination.

PMID- 29203426
TI  - Effects of structurally stabilized EGF and bFGF on wound healing in type I and
      type II diabetic mice.
AB  - : Diabetes mellitus comprises a multiple metabolic disorder that affects millions
      of people worldwide and consequentially poses challenges for clinical treatment.
      Among the various complications, diabetic ulcer constitutes the most prevalent
      associated disorder and leads to delayed wound healing. To enhance wound healing
      capacity, we developed structurally stabilized epidermal growth factor (ST-EGF)
      and basic fibroblast growth factor (ST-bFGF) to overcome limitations of
      commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life
      and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was
      toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF.
      We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a
      biocompatible carrier, and tested the effectiveness of this system in promoting
      wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded
      with 0.3 MUg/cm2 ST-EGF or 1 MUg/cm2 ST-bFGF showed a more rapid rate of tissue
      repair as compared to the control in type I and II diabetes models. Our results
      indicate that an HDC matrix loaded with 0.3 MUg/cm2 ST-EGF or 1 MUg/cm2 ST-bFGF
      can promote wound healing in diabetic ulcers and are suitable for use in wound
      dressings owing to their stability for long periods at room temperature.
      STATEMENT OF SIGNIFICANCE: Various types of dressing materials loaded with growth
      factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair.
      However, such growth factor-loaded materials have several limitations for use as
      therapeutic agents in healing-impaired diabetic wounds. To overcome these
      limitations, we have developed new materials containing structurally stabilized
      EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly
      developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing
      [HCD] matrix), we applied these matrices in type I and type II diabetic wounds.
      Notably, these matrices were able to accelerate wound healing including re
      epithelialization, neovascularization, and collagen deposition. Consequentially,
      these ST-EGF and ST-bFGF-loaded HCD matrix may be used as future therapeutic
      agents in patients with diabetic foot ulcers.

PMID- 29203428
TI  - Calibration by commutable control materials is able to reduce inter-method
      differences of current high-performance methods for HbA2.
AB  - BACKGROUND: Most of the current methods used for the determination of HbA2 seem
      not well aligned. A comparison among the best performing techniques and the
      commutability of some control materials currently available and under development
      has been evaluated. METHODS: Forty blood samples were analyzed in duplicate over
      two separate days by different HPLC and capillary electrophoresis systems. The
      commutabilities of different control materials (NIBSC WHO reagent, Bio-Rad
      Lyphochek, and home prepared lyophilized controls RP1-3) have been assessed by
      analyzing the controls in quadruplicate over two consecutive days together with
      the blood samples. RESULTS: The mean within-run imprecision of HbA2 measurement
      on blood samples (CV, %) was between 0.6% and 10.1% for HbA2 values <3.5%, and
      between 1.1 and 3.1 for HbA2>=3.5%. The different methods were highly correlated
      (r between 0.9941 and 0.9995) although biased each other. The NIBSC WHO reagent
      was found not commutable in 15 over 28 comparisons, the Lyphochek 2 in 18/28, and
      RP3 in 4/28. Recalibration of all methods by RP1 and RP2 materials was able to
      reduce the overall variability from 6.8% to 3.4% at HbA2<=3.0% and from 6.7% to
      3.0% at HbA2>=4.6%. CONCLUSION: The use of adequate commutable control materials
      as calibrators may reduce the inter-method variability of routine methods to an
      extent closer to the current analytical goals of bias based on biological
      variability.

PMID- 29203427
TI  - The association between plasma homocysteine and ambulatory blood pressure
      variability in patients with untreated hypertension.
AB  - BACKGROUND: Both homocysteine (Hcy) and blood pressure variability (BPV) are
      independent predictors of stroke, however, their relationship is rarely evaluated
      before. This study aimed to investigate the association Hcy and ambulatory BPV in
      subjects with untreated primary hypertension. METHODS: A total of 252 eligible
      patients were recruited. Plasma Hcy was measured and 24-h ambulatory blood
      pressure monitoring was performed for each subject. The systolic and diastolic
      BPV values were calculated as the SD of individual blood pressure values during
      24h, daytime and nighttime, and then stratified by the tertiles of Hcy
      concentration (T1 to T3). Univariate and multivariate linear regression models
      were used to assess the relationships between Hcy tertiles and BPV variables.
      RESULTS: The mean values of Hcy from T1 to T3 were 7.51+/-1.21MUmol/l, 11.09+/
      1.07MUmol/l and 19.14+/-6.26MUmol/l, respectively. Systolic and diastolic mean
      blood pressures were similar among subjects with different Hcy tertiles. However,
      both systolic and diastolic BPV variables, no matter in 24-h, daytime or
      nighttime, were increasing significantly along with the rises in Hcy tertiles
      (all p<0.05 for linear trends analysis). Multivariate linear regression analysis
      indicated that Hcy tertiles were significantly associated with BPV variables,
      independently of mean blood pressures other confounding factors. In subgroup
      analysis, the associations between Hcy tertiles and BPV variables were enhanced
      by the increased risk stratification of hypertension. CONCLUSIONS: Plasma Hcy was
      positively and independently associated with ambulatory BPV in patients with
      untreated hypertension.

PMID- 29203429
TI  - Oxidative stress in urea cycle disorders: Findings from clinical and basic
      research.
AB  - Inborn errors of metabolism (IEM) comprise a group of over 600 disorders, each
      with a specific metabolic impairment due to a genetic defect. Urea cycle
      disorders (UCD) are IEM that affect the nitrogen disposal system, leading to
      hyperammonemia and the accumulation of other toxic metabolites in tissues of
      affected patients. UCD arise from mutations in the genes coding any of the
      enzymes participating in the urea cycle, either directly or as regulators of this
      pathway, causing severe respiratory alkalosis. Considering that the exact
      mechanisms underlying the damage found in UCD, the purpose of this minireview is
      to obtain data and search for links between UCD and oxidative stress, a
      phenomenon common to several IEM. In vitro studies and animal models of UCD
      suggest that, not only the accumulation of ammonia, but also of the other
      metabolites involved in each UCD may impair redox status. Nitric oxide metabolism
      also seems to play an interesting role in the maintenance of redox balance in
      these conditions. Clinical research provides little information on the subject,
      but, studies appear to support the role of oxidative stress in pathologic
      mechanisms of UCD.

PMID- 29203430
TI  - Optimization of perioperative management of proximal femoral fracture in the
      elderly.
AB  - Proximal femoral fracture in elderly subjects is a major event that is life
      threatening in the medium-to-long term. Advanced age, male gender and number of
      comorbidities largely account for high mortality and require geriatric expertise.
      Protein-energy malnutrition and bone demineralization increase mortality.
      Mortality can, on the other hand, be reduced by acting on two variables
      accessible to medical intervention: daily activities and nutritional status.
      Functional and neurocognitive assessment allow the risk of dependency to be
      evaluated, and global geriatric work-up can prevent sudden breakdown of
      homeostasis. In the emergency setting, pain is to be alleviated, polymedication
      and anticoagulation therapy checked, and instability (notably cardiac and
      pulmonary) and confusion syndrome screened for on geriatric and anesthesiologic
      opinions. Surgery should be implemented without delay, within 48hours of
      admission, preferably using multimodal anesthesia. The technique should be geared
      to allow early weight-bearing and mobilization. The most comprehensive care plan
      involves team-work between emergency physicians, surgeons, orthopedic
      specialists, anesthesiologists, geriatricians, pharmacists, rehabilitation
      specialists and nursing staff, to reduce mortality and readmission and improve
      functional results. Post-fracture coordination seeks to prevent falls and further
      fractures and to treat bone demineralization.

PMID- 29203431
TI  - Surgical reduction of congenital hip dislocation.
AB  - Surgical reduction of congenital hip dislocation is technically challenging. In
      our practice, surgical reduction is usually reserved for patients who have failed
      non-operative treatment, which is the first-line strategy. However, primary
      surgery may be indicated if the dislocation is diagnosed late and can be
      performed until 8 years of age. The reduction step is crucial. It starts with
      painstaking exposure of the capsule. Identifying the lower part of the acetabulum
      is the key to accurate repositioning of the epiphysis. The main intra-articular
      procedures are resection of the ligament teres, adipose tissue within the
      acetabular cavity, and transverse acetabular ligament; and eversion of the
      radially incised limbus. In patients younger than 1 year of age, surgical
      reduction can be performed via the anterior approach or, in some cases, the
      obturator approach. No complementary steps are needed. If the diagnosis is made
      late, in contrast, reduction of the hip must be combined with corrective
      procedures on the femur and acetabulum designed to stabilise the reduction before
      the capsulorrhaphy, with the goal of optimising hip stability and minimising the
      risk of residual dysplasia. Femoral shortening and derotation osteotomy was
      classically reserved for children older than 3 years but has now been shown to be
      a useful and prudent procedure in younger patients. This osteotomy decreases
      pressure on the epiphysis, facilitates the reduction, and diminishes the risk of
      recurrence and avascular necrosis of the femoral head, which are the two dreaded
      complications. The outcome depends on the care directed to the procedure and on
      the quality of postoperative management.

PMID- 29203432
TI  - Cutibacterium acnes prosthetic joint infection: Diagnosis and treatment.
AB  - Cutibacterium acnes is a commensal skin bacterium, regularly implicated in
      prosthetic joint infection, particularly of the shoulder. Diagnosis has been
      improved by progress in bacteriological techniques: longer culture time, liquid
      medium culture, MALDI-TOF mass spectrography, and universal 16S rRNA PCR,
      associated by some authors to sonication of ablated implants. C. acnes
      pathogenicity involves many virulence factors, notably including biofilm
      formation. C. acnes may lead to infection that is clinically evident or,
      frequently, relatively asymptomatic. C. acnes is an anaerobic Gram-positive
      bacterium, susceptible to many antibiotics that are regularly used in bone and
      joint infection: beta-lactams, quinolone, rifampicin and clindamycin. It shows
      increasing resistance to clindamycin and natural resistance to metronidazole.
      Treatment is medical and surgical, associating synovectomy or complete 1- or 2
      step revision depending on time to treatment, and antibiotic therapy. Antibiotic
      therapy is typically for three months with an initial 2-6 weeks' intravenous
      phase. Prognosis is generally favorable with well-conducted treatment. Late
      discovery of positive samples after apparently aseptic implant change is an at
      risk situation, usually managed by antibiotic therapy, but with late initiation
      and hence increased risk of failure. Adverse secondary progression requires
      repeat revision under good conditions.

PMID- 29203433
TI  - Management of soft tissue tumors of the musculoskeletal system.
AB  - A palpable mass in the musculoskeletal system is a common reason for
      consultation. The main issue is that a malignant tumor must not be missed.
      Inappropriate initial treatment can have direct consequences on the risk of local
      recurrence, the patient's future function and life expectancy. A mass more than
      5cm in diameter, a subfascial location and a recent increase in size are signs
      that should lead the physician to question whether the lesion is truly benign and
      to carry out diagnostic examinations. MRI is the gold standard imaging exam.
      Biopsy, which is now mainly percutaneous and imaging-guided, must be performed
      for any subfascial mass more than 5cm long or a smaller mass with a high risk of
      postoperative functional sequelae. Referring the patient to a specialized cancer
      center has direct benefits on the patient's recurrence-free survival and reduces
      time lost during the diagnostic and treatment phases. For malignant tumors,
      surgical treatment requires resection margins that comply with cancer guidelines.
      Preservation of the limb and its function may require multidisciplinary
      reconstruction techniques. Pre- or post-operative radiation therapy or
      chemotherapy should be proposed only after discussion in a multidisciplinary team
      meeting.

PMID- 29203434
TI  - Efficacy and rapid activity of omalizumab retreatment in chronic spontaneous
      urticaria.

PMID- 29203435
TI  - Occurrence of vismodegib-induced cramps (muscular spasms) in the treatment of
      basal cell carcinoma: A prospective study in 30 patients.

PMID- 29203436
TI  - A cross-sectional survey of long-term outcomes for patients with diffuse
      capillary malformation with overgrowth.

PMID- 29203437
TI  - Effect of alcohol-based hand rub on hand microbiome and hand skin health in
      hospitalized adult stem cell transplant patients: A pilot study.

PMID- 29203438
TI  - Risk of venous thromboembolism in patients with mycosis fungoides and
      parapsoriasis: A Danish nationwide population-based cohort study.
AB  - BACKGROUND: Mycosis fungoides (MF) and parapsoriasis are characterized by
      malignant proliferation and chronic inflammation, which may affect the risk for
      venous thromboembolism (VTE). OBJECTIVES: To examine the risk for VTE in patients
      with MF and parapsoriasis. METHODS: We conducted a nationwide population-based
      cohort study in Denmark to examine the relative risk (RR) of VTE in 525 patients
      with MF and 634 patients with parapsoriasis compared with that in sex- and age
      matched controls from the general population. RESULTS: In patients with MF, the
      10-year absolute risk for VTE was 3.4% (95% confidence interval [CI], 2.0-5.4).
      The adjusted RRs were 2.41 (95% CI, 1.49-3.90) for VTE and 4.01 (95% CI, 2.16
      7.46) for pulmonary embolism. Notably, within the first 5 years after diagnosis
      with MF, the RR of pulmonary embolism was increased 6.7-fold (to 6.71 [95% CI,
      2.86-15.72]). Patients with parapsoriasis had a 2.7-fold increased RR of VTE (to
      2.67 [95% CI, 1.32-5.40]) in the absence of other established VTE risk factors.
      LIMITATIONS: We had no information regarding disease stage of MF and prescribed
      drugs. CONCLUSION: Patients with MF and parapsoriasis had an increased RR of VTE,
      although the absolute risk remained low. These findings should increase awareness
      of comorbidities in patients with MF and parapsoriasis.

PMID- 29203439
TI  - An age-dependent interaction between sex and geographical UV index in melanoma
      risk.
AB  - BACKGROUND: UV exposure may not equally impact melanoma development in different
      sexes and ages. Whether and how these factors interact with each other in
      melanoma risk is unknown. OBJECTIVE: This study attempts to estimate interactions
      among UVI, sex and age in melanoma risk. METHODS: Melanoma incidence data was
      collected from 42 cancer registries. Geographical UV index (UVI) was collected
      from local satellite stations. Negative binomial regression models were used to
      estimate the impact of each risk factor and their interactions. RESULTS: Sex, UVI
      and age, as well as interactions between any two of these factors were
      significantly associated with melanoma risk. In younger age groups, the female
      sex is an independent risk factor for melanoma that is not impacted by ambient UV
      exposure. In older age groups, however, the female sex interacts with UV exposure
      as a risk factor, exhibiting a protective effect. The switching age category is
      45-49, which correlates with dramatic hormonal changes. LIMITATIONS: the
      interaction between sex and UVI is measured at an ecological level. CONCLUSION:
      The interaction between sex and UVI is age-dependent. The female sex is an
      independent risk factor for early onset melanoma, but the female sex also
      protects against UV-associated melanoma in older age groups.

PMID- 29203442
TI  - N-3 PUFA diet enrichment prevents amyloid beta-induced depressive-like phenotype.
AB  - Among neuropsychiatric diseases, depression is one of the most prevalent. Many
      pathologies have been indicated as comorbid with depression and in particular,
      neurodegenerative disorders such as Alzheimer's diseases (AD). In this regard,
      several evidences endorse a strong relationship between depression and AD, so
      much that this mental illness has been proposed either as a risk factor for AD or
      as a prodromic AD phase. Furthermore, amyloid beta (Abeta) peptide, the main
      constituent of amyloid plaques commonly considered the principal hallmark of AD
      brains, has been shown to be increased, in its soluble form, in depressed
      patients. Accordingly, we have previously found that Abeta,
      intracerebroventricularly (i.c.v.) injected, is able to evoke a depressive-like
      profile in rats accompanied by low cortical serotonin and reduced neurotrophin
      content. Taking into account the great increase in AD and depression prevalence,
      many environmental factors have been under study, particularly dietary factors,
      and the role of polyunsaturated fatty acids (PUFA) is becoming central in this
      field of research. Thus, aim of the present study was to evaluate the
      neurobehavioral effects of lifelong exposure to either n-3 PUFA rich or n-3 PUFA
      poor diet after Abeta central administration. Results showed that n-3 PUFA
      enriched diet prevented the Abeta- induced depressive-like behaviors, as reveled
      by the reduction in the immobility time in the FST test. Furthermore, n-3 PUFA
      rich diet exposure reverted also serotonin and neurotrophin level reduction in
      prefrontal cortex of Abeta treated rats. Taken together, our data support the
      concept that supplementation of diet with n-3 PUFA represents a valid approach to
      reduce the risk of developing depressive symptoms, as well as reducing the risk
      of Abeta-related pathologies, such as AD.

PMID- 29203443
TI  - Examination of emotion-induced changes in eating: A latent profile analysis of
      the Emotional Appetite Questionnaire.
AB  - It is now recognized that emotions can influence food intake. While some people
      report eating less when distressed, others report either no change of eating or
      eating more in the same condition. The question whether this interindividual
      variability also occurs in response to positive emotions has been overlooked in
      most studies on Emotional Eating (EE). Using the Emotional Appetite Questionnaire
      (EMAQ) and Latent Profile Analysis, this study aimed to examine the existence of
      latent emotion-induced changes in eating profiles, and explore how these profiles
      differ by testing their relations with 1) age and sex, 2) BMI and risk for eating
      disorders (ED) and 3) factors that are known to be associated with EE such as
      perceived positive/negative feelings, depression, anxiety, stress symptoms and
      impulsivity. Among 401 university students (245 females) who completed the EMAQ,
      3 profiles emerged (P1:11.2%, P2:60.1%, P3:28.7%), with distinct patterns of
      eating behaviors in response to negative emotions and situations but few
      differences regarding positive ones. Negative emotional overeaters (P1) and
      negative emotional undereaters (P3) reported similar levels of emotional distress
      and positive feelings, and were at greater risk for ED. However, the people in
      the former profile i) reported decreasing their food intake in a positive
      context, ii) were in majority females, iii) had higher BMI and iv) were more
      prone to report acting rashly when experiencing negative emotions. Our findings
      suggest that a person-centred analysis of the EMAQ scores offers a promising way
      to capture the inter-individual variability of emotionally-driven eating
      behaviors. These observations also add to the growing literature underscoring the
      importance of further investigating the role of different facets of impulsivity
      in triggering overeating and to develop more targeted interventions of EE.

PMID- 29203444
TI  - Stress and eating behaviors in children and adolescents: Systematic review and
      meta-analysis.
AB  - It is well established that stress is linked to changes in eating behaviors.
      Research using adult populations has shown that stress is associated with both
      increases and decreases in the amount and type of food consumed. However, due to
      a lack of research reviews, the relationship between stress and eating behaviors
      in children is unclear. This systematic research review and meta-analysis aimed
      to identify whether stress is associated with healthy and unhealthy eating
      behaviors in children aged 8-18 years. Studies were included in the review if
      they measured stress and included a measure of food consumption. All unique
      studies retrieved (N = 28,070) were assessed for their eligibility at title,
      abstract and full text levels. A total of 13 studies were included in the final
      review and data were analysed using Comprehensive Meta-Analysis. Using random
      effects modelling, overall stress was not associated with a change in overall
      eating behaviors. However, additional analyses indicated stress was associated
      with unhealthy eating behaviors in both younger (Hedge's g = 0.283, p < 0.001)
      and older (Hedge's g = 0.274, p = 0.001) children. In contrast, stress was not
      associated with healthy eating behaviors in younger children (Hedge's g = 0.093,
      p = 0.156), but was negatively associated with healthy eating behaviors in older
      children (Hedge's g = -0.384, p < 0.001). The current findings are concerning as
      they suggest the impact of stress on unhealthy eating may begin as early as 8 or
      9 years old. Future research ought to investigate further the role of
      psychological, behavioral and endocrine factors in the development of stress
      related eating in children.

PMID- 29203441
TI  - Therapeutic targeting of oncogenic transcription factors by natural products in
      eye cancer.
AB  - Carcinogenesis has a multifactorial etiology, and the underlying molecular
      pathogenesis is still not entirely understood, especially for eye cancers.
      Primary malignant intraocular neoplasms are relatively rare, but delayed
      detection and inappropriate management contribute to poor outcomes. Conventional
      treatment, such as orbital exenteration, chemotherapy, or radiotherapy, alone
      results in high mortality for many of these malignancies. Recent sequential
      multimodal therapy with a combination of high-dose chemotherapy, followed by
      appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has
      helped dramatically improve management. Transcription factors are proteins that
      regulate gene expression by modulating the synthesis of mRNA. Since transcription
      is a dominant control point in the production of many proteins, transcription
      factors represent key regulators for numerous cellular functions, including
      proliferation, differentiation, and apoptosis, making them compelling targets for
      drug development. Natural compounds have been studied for their potential to be
      potent yet safe chemotherapeutic drugs. Since the ancient times, plant-derived
      bioactive molecules have been used to treat dreadful diseases like cancer, and
      several refined pharmaceutics have been developed from these compounds.
      Understanding targeting mechanisms of oncogenic transcription factors by natural
      products can add to our oncologic management toolbox. This review summarizes the
      current findings of natural products in targeting specific oncogenic
      transcription factors in various types of eye cancer.

PMID- 29203440
TI  - CAR-T cells and combination therapies: What's next in the immunotherapy
      revolution?
AB  - Cancer immunotherapies are dramatically reshaping the clinical management of
      oncologic patients. For many of these therapies, the guidelines for
      administration, monitoring, and management of associated toxicities are still
      being established. This is especially relevant for adoptively transferred,
      genetically-modified T cells, which have unique pharmacokinetic properties, due
      to their ability to replicate and persist long-term, following a single
      administration. Furthermore, in the case of CAR-T cells, the use of synthetic
      immune receptors may impact signaling pathways involved in T cell function and
      survival in unexpected ways. We, herein, comment on the most salient aspects of
      CAR-T cell design and clinical experience in the treatment of solid tumors. In
      addition, we discuss different possible scenarios for combinations of CAR-T cells
      and other treatment modalities, with a special emphasis on kinase inhibitors,
      elaborating on the strategies to maximize synergism. Finally, we discuss some of
      the technologies that are available to explore the molecular events governing the
      success of these therapies. The young fields of synthetic and systems biology are
      likely to be major players in the advancement of CAR-T cell therapies, providing
      the tools and the knowledge to engineer patients' T lymphocytes into intelligent
      cancer-fighting micromachines.

PMID- 29203445
TI  - Rapid monitoring of vancomycin-resistant Enterococcus faecium in hospital
      departments by repetitive element palindromic polymerase chain reaction.
AB  - BACKGROUND: The current increase in nosocomial infections caused by vancomycin
      resistant enterococci (VRE) warrants improvement of detection methods and hygiene
      measures. Knowledge of the local epidemiology is important for monitoring
      compliance of medical personnel with hygiene measures. AIM: To evaluate semi
      automated repetitive element palindromic polymerase chain reaction (rep-PCR) for
      rapid molecular typing of VRE. METHODS: Primary VRE isolates were collected
      during an observation period of one year and retrospectively typed by rep-PCR.
      Molecular typing was performed on isolates from two departments with elevated VRE
      rates and patients with increased risk for systemic VRE infections. Typing
      results were correlated with temporal and spatial information on patient moves,
      VRE laboratory results and multi-locus sequence typing (MLST). FINDINGS:
      Approximately 70% of VRE isolates within a department could be assigned to
      similarity clusters. Spread of VRE was limited to the individual departments.
      There was no evidence for spread of endemic VRE strains within the geographical
      catchment area of the hospital. Our results demonstrate the utility of rep-PCR
      typing on a department level. However, a Diversilab(r) threshold of >=98% had to
      be applied to claim similarity, and suspected transmissions needed to be
      confirmed by vanA/B genotyping and compiled information on spatial and temporal
      patient contact. MLST verified the findings. CONCLUSION: Spread of predominantly
      detected vancomycin-resistant Enterococcus faecium was limited to the department
      level with no evidence for wider dissemination within the hospital. Well
      standardized and validated (semi-)automated rep-PCR systems are useful for rapid
      detection of possible VRE transmission. However, suspected transmissions need to
      be confirmed by clinical and microbiological parameters.

PMID- 29203447
TI  - Reducing Escherichia coli bacteraemia associated with catheter-associated urinary
      tract infections in the secondary care setting.

PMID- 29203446
TI  - Update on Clostridium difficile from the European Congress of Clinical
      Microbiology and Infectious Diseases (ECCMID), Vienna, Austria, April 22-25,
      2017.

PMID- 29203448
TI  - Surface disinfection challenges for Candida auris: an in-vitro study.
AB  - The emerging pathogenic multidrug-resistant yeast Candida auris is an important
      source of healthcare-associated infections and of growing global clinical
      concern. The ability of this organism to survive on surfaces and withstand
      environmental stressors creates a challenge for eradicating it from hospitals. A
      panel of C. auris clinical isolates was evaluated on different surface
      environments against the standard disinfectant sodium hypochlorite and high-level
      disinfectant peracetic acid. C. auris was shown to selectively tolerate
      clinically relevant concentrations of sodium hypochlorite and peracetic acid in a
      surface-dependent manner, which may explain its ability to successfully persist
      within the hospital environment.

PMID- 29203449
TI  - Dietary leucine modulates growth performance, Nrf2 antioxidant signaling pathway
      and immune response of juvenile blunt snout bream (Megalobrama amblycephala).
AB  - The present study assessed the effects of dietary leucine on growth performance,
      antioxidant status and immunity in juvenile blunt snout bream. Fish were fed six
      practical diets of graded leucine levels ranging from 0.90% to 2.94% of dry basis
      for 8 weeks. Trail results showed that compared to control group (0.90%), 1.72%
      dietary leucine level significantly improved final weight (FW), weight gain rate
      (WG) and specific growth rate (SGR), and significantly lowered feed conversion
      ratio (FCR). Based on WG and SGR, the optimal dietary leucine level was obtained
      at 1.40% and 1.56%, respectively. Whole body crude lipid and protein contents
      were improved with increasing dietary leucine up to 2.14% and thereafter showed a
      downward trend, while whole body moisture content showed a converse trend. No
      significant change was found in whole body ash content. 1.72% dietary leucine
      level significantly improved the antioxidant capacity of fish by regulating the
      plasma superoxide dismutase (SOD) activity, glutathione peroxidase (GPx)
      activity, total antioxidant capacity (T-AOC) activity, catalase (CAT) activity,
      aspartate aminotransferase (AST) activities and malondialdehyde (MDA) content,
      furthermore, 1.72% dietary leucine level also significantly improved the
      antioxidant genes expressions of associated with Nrf2 signaling pathway by
      regulating heme oxygenase-1 (HO-1), GPx, copperezinc superoxide dismutase (Cu/Zn
      SOD), manganese superoxide dismutase (Mn-SOD), 2.14% dietary leucine levels also
      significantly improved glutathione transferase (GST) mRNA level. Dietary leucine
      levels significantly affected plasma immunity parameters such as the contents of
      plasma complement component 3 (C3), immunoglobulin M (IgM) and lowered the
      hepatopancreas genes expressions of pro-inflammatory factor by regulating
      interleukin 1beta (IL-1beta), interleukin 8 (IL-8) and tumour necrosis factor
      alpha (TNF-alpha) mRNA levels. The present study indicated that optimal dietary
      leucine level plays an important role in improving growth, enhancing antioxidant
      and immune status to maintain the health in juvenile blunt snout bream.

PMID- 29203450
TI  - The drug discrimination assay: Interpretative value of partial generalization for
      drug schedule control actions.
AB  - The U.S. Food & Drug Administration (FDA) has issued a final guidance document on
      the preclinical determination of abuse potential that must be conducted in
      animals for all new molecular entities (NMEs) submitted for a new drug
      application (NDA). Under statutory restrictions government guidance documents
      serve only as a guide or an expression of the agency's current thinking on the
      topic. Guidelines do not legally bind the agency or its registrants to any
      content in the guidance. There are no statutory (legal) descriptions of what
      study designs or methodology must be submitted to the Drug Enforcement
      Administration with respect to drug scheduling review. This paper describes the
      utility of an alternate method used, worldwide, to assess the internal subjective
      effects of drugs to predict the abuse liability that provides additional
      information to address the relative aspects of that liability.

PMID- 29203451
TI  - An improved CPRG colorimetric ligand-receptor signal transduction assay based on
      beta-galactosidase activity in mammalian BWZ-reporter cells.
AB  - INTRODUCTION: Reporter cells expressing a chimeric receptor that activates a
      reporter can be used for screening ligand-mediated signal transduction. In this
      study, we used reporter cells harboring an NFAT/lacZ construct that express beta
      galactosidase when the chimeric receptor is stimulated. A colorimetric beta
      galactosidase substrate, chlorophenol-red beta-d-galactopyranoside (CPRG), was
      used to detect enzymatic activity. Sub-optimal conditions have unfortunately
      extensively been reported with such reporter-based beta-galactosidase assays.
      Here, we aimed to improve the CPRG-based colorimetric assay such that receptor
      ligands could be effectively screened with reporter cells. METHODS: After
      stimulation of reporter cells, we determined beta-galactosidase activity by
      absorbance measurement of beta-galactosidase-dependent CPRG hydrolysis. We
      systematically examined each component in a standard lysis buffer most commonly
      reported for this type of reporter cells. Furthermore, we evaluated literature in
      the field. RESULTS: An increased CPRG substrate concentration combined with a
      different detergent, Saponin, and an optimal wavelength recording markedly
      increased the sensitivity for the detection of beta-galactosidase activity (~4
      fold increase). Moreover, the improved protocol resulted in increased linear time
      dependent recording of enzymatic activity once cells had been lysed, and a more
      stable and reproducible assay to detect a ligand-stimulus with the reporter
      cells. The optimal time length of exposure to a stimulus was ligand-dependent.
      DISCUSSION: In conclusion, we provide an improved protocol with an optimized
      lysis buffer that gives up to a six-fold higher and more robust specific signal
      when NFAT/lacZ-based receptor-expressing reporter cells are exposed to a
      stimulus.

PMID- 29203452
TI  - A spatio-temporal reference model of the aging brain.
AB  - Both normal aging and neurodegenerative disorders such as Alzheimer's disease
      (AD) cause morphological changes of the brain. It is generally difficult to
      distinguish these two causes of morphological change by visual inspection of
      magnetic resonance (MR) images. To facilitate making this distinction and thus
      aid the diagnosis of neurodegenerative disorders, we propose a method for
      developing a spatio-temporal model of morphological differences in the brain due
      to normal aging. The method utilizes groupwise image registration to characterize
      morphological variation across brain scans of people with different ages. To
      extract the deformations that are due to normal aging we use partial least
      squares regression, which yields modes of deformations highly correlated with
      age, and corresponding scores for each input subject. Subsequently, we determine
      a distribution of morphologies as a function of age by fitting smooth percentile
      curves to these scores. This distribution is used as a reference to which a
      person's morphology score can be compared. We validate our method on two
      different datasets, using images from both cognitively normal subjects and
      patients with Alzheimer disease (AD). Results show that the proposed framework
      extracts the expected atrophy patterns. Moreover, the morphology scores of
      cognitively normal subjects are on average lower than the scores of AD subjects,
      indicating that morphology differences between AD subjects and healthy subjects
      can be partly explained by accelerated aging. With our methods we are able to
      assess accelerated brain aging on both population and individual level. A spatio
      temporal aging brain model derived from 988 T1-weighted MR brain scans from a
      large population imaging study (age range 45.9-91.7y, mean age 68.3y) is made
      publicly available at www.agingbrain.nl.

PMID- 29203453
TI  - A transferable high-intensity intermittent exercise improves executive
      performance in association with dorsolateral prefrontal activation in young
      adults.
AB  - Although growing attention has been drawn to attainable, high-intensity
      intermittent exercise (HIE)-based intervention, which can improve cardiovascular
      and metabolic health, for sedentary individuals, there is limited information on
      the impact and potential benefit of an easily attainable HIE intervention for
      cognitive health. We aimed to reveal how acute HIE affects executive function
      focusing on underlying neural substrates. To address this issue, we examined the
      effects of acute HIE on executive function using the color-word matching Stroop
      task (CWST), which produces a cognitive conflict in the decision-making process,
      and its neural substrate using functional near infrared spectroscopy (fNIRS).
      Twenty-five sedentary young adults (mean age: 21.0 +/- 1.6 years; 9 females)
      participated in two counter-balanced sessions: HIE and resting control. The HIE
      session consisted of two minutes of warm-up exercise (50 W load at 60 rpm) and
      eight sets of 30 s of cycling exercise at 60% of maximal aerobic power (mean: 127
      W +/- 29.5 load at 100 rpm) followed by 30 s of rest on a recumbent-ergometer.
      Participants performed a CWST before and after the 10-minute exercise session,
      during both of which cortical hemodynamic changes in the prefrontal cortex were
      monitored using fNIRS. Acute HIE led to improved Stroop performance reflected by
      a shortening of the response time related to Stroop interference. It also evoked
      cortical activation related to Stroop interference on the left-dorsal-lateral
      prefrontal cortex (DLPFC), which corresponded significantly with improved
      executive performance. These results provide the first empirical evidence using a
      neuroimaging method, to our knowledge, that acute HIE improves executive
      function, probably mediated by increased activation of the task-related area of
      the prefrontal cortex including the left-DLPFC.

PMID- 29203454
TI  - Framework for shape analysis of white matter fiber bundles.
AB  - Diffusion imaging coupled with tractography algorithms allows researchers to
      image human white matter fiber bundles in-vivo. These bundles are three
      dimensional structures with shapes that change over time during the course of
      development as well as in pathologic states. While most studies on white matter
      variability focus on analysis of tissue properties estimated from the diffusion
      data, e.g. fractional anisotropy, the shape variability of white matter fiber
      bundle is much less explored. In this paper, we present a set of tools for shape
      analysis of white matter fiber bundles, namely: (1) a concise geometric model of
      bundle shapes; (2) a method for bundle registration between subjects; (3) a
      method for deformation estimation. Our framework is useful for analysis of shape
      variability in white matter fiber bundles. We demonstrate our framework by
      applying our methods on two datasets: one consisting of data for 6 normal adults
      and another consisting of data for 38 normal children of age 11 days to 8.5
      years. We suggest a robust and reproducible method to measure changes in the
      shape of white matter fiber bundles. We demonstrate how this method can be used
      to create a model to assess age-dependent changes in the shape of specific fiber
      bundles. We derive such models for an ensemble of white matter fiber bundles on
      our pediatric dataset and show that our results agree with normative human head
      and brain growth data. Creating these models for a large pediatric longitudinal
      dataset may improve understanding of both normal development and pathologic
      states and propose novel parameters for the examination of the pediatric brain.

PMID- 29203455
TI  - Quantitative MRI provides markers of intra-, inter-regional, and age-related
      differences in young adult cortical microstructure.
AB  - Measuring the structural composition of the cortex is critical to understanding
      typical development, yet few investigations in humans have charted markers in
      vivo that are sensitive to tissue microstructural attributes. Here, we used a
      well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*,
      PD*) that differ in their sensitivity to facets of the tissue microstructural
      environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic
      ions, i.e., iron; PD*: free water content). Mapping these parameters across
      cortical regions in a young adult cohort (18-39 years, N = 93) revealed expected
      patterns of increased macromolecular content as well as reduced tissue water
      content in primary and primary adjacent cortical regions. Mapping across cortical
      depth within regions showed decreased expression of myelin and related processes 
      but increased tissue water content - when progressing from the grey/white to the
      grey/pial boundary, in all regions. Charting developmental change in cortical
      microstructure cross-sectionally, we found that parameters with sensitivity to
      tissue myelin (R1 & MT) showed linear increases with age across frontal and
      parietal cortex (change 0.5-1.0% per year). Overlap of robust age effects for
      both parameters emerged in left inferior frontal, right parietal and bilateral
      pre-central regions. Our findings afford an improved understanding of ontogeny in
      early adulthood and offer normative quantitative MR data for inter- and intra
      cortical composition, which may be used as benchmarks in further studies.

PMID- 29203457
TI  - Non-invasive estimation of [11C]PBR28 binding potential.
AB  - [11C]PBR28 is a PET radioligand used to estimate densities of the 18 kDa
      translocator protein (TSPO) in vivo. Since there is no suitable reference region,
      arterial blood samples are required for full quantification. Here, we evaluate a
      methodology for full quantification of [11C]PBR28 PET data that does not require
      either a reference region or blood samples. Simultaneous estimation (SIME) uses
      time-activity curves from several brain regions to estimate binding potential
      (BPND), a theoretically more sensitive outcome measure than total distribution
      volume. SIME can be employed with either a measured arterial input function (AIF)
      or a template input function (tIF) that has similar shape as the AIF, but with
      arbitrary amplitude. We evaluated the ability of SIME to detect group differences
      in TSPO densities using PET and arterial plasma data from 21 Alzheimer's disease
      (AD) patients and 15 controls that underwent [11C]PBR28 imaging. Regional BPND
      obtained with tIFs were compared to those obtained using measured AIFs. Standard
      kinetic modeling was also employed for comparison. The sensitivity of each method
      to detect group differences in TSPO densities were assessed by comparing
      estimated effect sizes between AD patients and controls. For this purpose, BPND
      estimated for one region with high pathological burden (inferior temporal
      cortex), and for one region with low pathological burden (cerebellum) was used.
      BPND estimates obtained with SIME and tIFs were close to identical to those
      obtained with AIF (3.0 +/- 21% difference, r2 = 0.78). In this dataset, the
      effect sizes between AD patients and controls for both SIME with AIF and SIME
      with tIF were similar (30.3%, p = 0.001 and 31.0%, p = 0.004, respectively) and
      were each greater than the effect size observed using the two-tissue compartment
      model (16.1%, p = 0.12). None of the tested methods showed difference in TSPO
      binding in cerebellum. These results demonstrate that BPND can be estimated for
      [11C]PBR28 using SIME, and may be useful in clinical studies. In addition,
      arterial sampling may not be necessary if tIFs can be reliably estimated.

PMID- 29203456
TI  - Non-invasive laminar inference with MEG: Comparison of methods and source
      inversion algorithms.
AB  - : Magnetoencephalography (MEG) is a direct measure of neuronal current flow; its
      anatomical resolution is therefore not constrained by physiology but rather by
      data quality and the models used to explain these data. Recent simulation work
      has shown that it is possible to distinguish between signals arising in the deep
      and superficial cortical laminae given accurate knowledge of these surfaces with
      respect to the MEG sensors. This previous work has focused around a single
      inversion scheme (multiple sparse priors) and a single global parametric fit
      metric (free energy). In this paper we use several different source inversion
      algorithms and both local and global, as well as parametric and non-parametric
      fit metrics in order to demonstrate the robustness of the discrimination between
      layers. We find that only algorithms with some sparsity constraint can
      successfully be used to make laminar discrimination. Importantly, local t
      statistics, global cross-validation and free energy all provide robust and
      mutually corroborating metrics of fit. We show that discrimination accuracy is
      affected by patch size estimates, cortical surface features, and lead field
      strength, which suggests several possible future improvements to this technique.
      This study demonstrates the possibility of determining the laminar origin of MEG
      sensor activity, and thus directly testing theories of human cognition that
      involve laminar- and frequency-specific mechanisms. This possibility can now be
      achieved using recent developments in high precision MEG, most notably the use of
      subject-specific head-casts, which allow for significant increases in data
      quality and therefore anatomically precise MEG recordings. SECTION: Analysis
      methods. CLASSIFICATIONS: Source localization: inverse problem; Source
      localization: other.

PMID- 29203458
TI  - Evaluating In-Car Movements in the Design of Mindful Commute Interventions:
      Exploratory Study.
AB  - BACKGROUND: The daily commute could be a right moment to teach drivers to use
      movement or breath towards improving their mental health. Long commutes, the
      relevance of transitioning from home to work, and vice versa and the privacy of
      commuting by car make the commute an ideal scenario and time to perform mindful
      exercises safely. Whereas driving safety is paramount, mindful exercises might
      help commuters decrease their daily stress while staying alert. Increasing
      vehicle automation may present new opportunities but also new challenges.
      OBJECTIVE: This study aimed to explore the design space for movement-based
      mindful interventions for commuters. We used qualitative analysis of simulated
      driving experiences in combination with simple movements to obtain key design
      insights. METHODS: We performed a semistructured viability assessment in 2 parts.
      First, a think-aloud technique was used to obtain information about a driving
      task. Drivers (N=12) were given simple instructions to complete movements
      (configural or breath-based) while engaged in either simple (highway) or complex
      (city) simulated urban driving tasks using autonomous and manual driving modes.
      Then, we performed a matching exercise where participants could experience
      vibrotactile patterns from the back of the car seat and map them to the prior
      movements. RESULTS: We report a summary of individual perceptions concerning
      different movements and vibrotactile patterns. Beside describing situations
      within a drive when it may be more likely to perform movement-based
      interventions, we also describe movements that may interfere with driving and
      those that may complement it well. Furthermore, we identify movements that could
      be conducive to a more relaxing commute and describe vibrotactile patterns that
      could guide such movements and exercises. We discuss implications for design such
      as the influence of driving modality on the adoption of movement, need for
      personal customization, the influence that social perception has on participants,
      and the potential role of prior awareness of mindful techniques in the adoption
      of new movement-based interventions. CONCLUSIONS: This exploratory study provides
      insights into which types of movements could be better suited to design mindful
      interventions to reduce stress for commuters, when to encourage such movements,
      and how best to guide them using noninvasive haptic stimuli embedded in the car
      seat.

PMID- 29203459
TI  - Mobile Phone Apps for Quality of Life and Well-Being Assessment in Breast and
      Prostate Cancer Patients: Systematic Review.
AB  - BACKGROUND: Mobile phone health apps are increasingly gaining attention in
      oncological care as potential tools for supporting cancer patients. Although the
      number of publications and health apps focusing on cancer is increasing, there
      are still few specifically designed for the most prevalent cancers diagnosed:
      breast and prostate cancers. There is a need to review the effect of these apps
      on breast and prostate cancer patients' quality of life (QoL) and well-being.
      OBJECTIVE: The purposes of this study were to review the scientific literature on
      mobile phone apps targeting breast or prostate cancer patients and involving QoL
      and well-being (anxiety and depression symptoms) and analyze the clinical and
      technological characteristics, strengths, and weaknesses of these apps, as well
      as patients' user experience with them. METHODS: We conducted a systematic review
      of peer-reviewed literature from The Cochrane Library, Excerpta Medica Database,
      PsycINFO, PubMed, Scopus, and MEDLINE to identify studies involving apps focused
      on breast and/or prostate cancer patients and QoL and/or well-being published
      between January 1, 2000, and July 12, 2017. Only trial studies which met the
      inclusion criteria were selected. The systematic review was completed with a
      critical analysis of the apps previously identified in the health literature
      research that were available from the official app stores. RESULTS: The
      systematic review of the literature yielded 3862 articles. After removal of
      duplicates, 3229 remained and were evaluated on the basis of title and abstract.
      Of these, 3211 were discarded as not meeting the inclusion criteria, and 18
      records were selected for full text screening. Finally, 5 citations were included
      in this review, with a total of 644 patients, mean age 52.16 years. Four studies
      targeted breast cancer patients and 1 focused on prostate cancer patients. Four
      studies referred to apps that assessed QoL. Only 1 among the 5 analyzed apps was
      available from the official app store. In 3 studies, an app-related intervention
      was carried out, and 2 of them reported an improvement on QoL. The lengths of the
      app-related interventions varied from 4 to 12 weeks. Because 2 of the studies
      only tracked use of the app, no effect on QoL or well-being was found.
      CONCLUSIONS: Despite the existence of hundreds of studies involving cancer
      focused mobile phone apps, there is a lack of rigorous trials regarding the QoL
      and/or well-being assessment in breast and/or prostate cancer patients. A strong
      and collective effort should be made by all health care providers to determine
      those cancer-focused apps that effectively represent useful, accurate, and
      reliable tools for cancer patients' disease management. TRIAL REGISTRATION:
      PROSPERO CRD42017073069;
      https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID= CRD42017073069
      (Archived by WebCite at http://www.webcitation.org/6v38Clb9T).

PMID- 29203460
TI  - Treatment of Low Back Pain with a Digital Multidisciplinary Pain Treatment App:
      Short-Term Results.
AB  - BACKGROUND: Even though modern concepts of disease management of unspecific low
      back pain (LBP) postulate active participation of patients, this strategy is
      difficult to adapt unless multidisciplinary pain therapy is applied. Recently,
      mobile health solutions have proven to be effective aides to foster self
      management of many diseases. OBJECTIVE: The objective of this paper was to report
      on the retrospective short-term results of a digital multidisciplinary pain app
      for the treatment of LBP. METHODS: Kaia is a mobile app that digitalizes
      multidisciplinary pain treatment and is in the market as a medical product class
      I. For the current study, the data of anonymized Kaia users was retrospectively
      analyzed. User data were evaluated for 12 weeks regarding duration of use and
      effect on in-app user reported pain levels, using the numerical rating scale
      (NRS), depending on whether LBP was classified as acute, subacute, or chronic
      back pain according to current guidelines. RESULTS: Data of 180 users were
      available. The mean age of the users was 33.9 years (SD 10.9). Pain levels
      decreased from baseline NRS 4.8 to 3.75 for all users at the end of the
      observation period. Users who completed 4, 8, or 12 weeks showed an even more
      pronounced decrease in pain level NRS (baseline 4.9 [SD 1.7] versus 3.6 [SD 1.5]
      at 4 weeks; baseline 4.7 [SD 1.8] versus 3.2 [SD [2.0] at 8 weeks; baseline 4.6
      [SD 2.2] versus 2.6 [SD 2.0] at 12 weeks). In addition, subgroup analysis of
      acute, subacute, or chronic classification revealed no significant main effect of
      group (P>.30) on the reduction of pain. Conclusions: This retrospective study
      showed that in a pre-selected population of app users, an app digitalizing
      multidisciplinary rehabilitation for the self-management of LBP reduced user
      reported pain levels significantly. The observed effect size was clinically
      relevant. Ongoing prospective randomized controlled trials (RCTs) will adjust for
      potential bias and selection effects. CONCLUSIONS: This retrospective study
      showed that in a pre-selected population of app users, an app digitalizing
      multidisciplinary rehabilitation for the self-management of LBP reduced user
      reported pain levels significantly. The observed effect size was clinically
      relevant. Ongoing prospective RCTs will adjust for potential bias and selection
      effects.

PMID- 29203462
TI  - Ban evergreening and restricting generics to reduce drug prices, says US academy.

PMID- 29203463
TI  - Contractile reserve as a predictor of prognosis in non-ischaemic systolic heart
      failure: a systematic review and meta-analysis.
AB  - OBJECTIVE: Patients with non-ischaemic systolic heart failure (HF) and idiopathic
      dilated cardiomyopathy (DCM) are a heterogenous group with varied morbidity and
      mortality. Prognostication in this group is challenging. We performed a
      systematic review and meta-analysis to examine the significance of the presence
      of contractile reserve as assessed via stress imaging on mortality and
      hospitalisation. METHODS: A search for studies that non-invasively assessed
      contractile reserve in patients with DCM or non-ischaemic HF with reduced
      ejection fraction; stress imaging with follow up data comparing outcomes. A range
      of imaging modalities and stressors were included. We examined primary end points
      of mortality; secondary endpoints of combined cardiovascular events including HF
      progression or hospitalisation. Our analysis compared endpoints in patients with
      contractile reserve and those without. RESULTS: Nine prospective cohort studies
      were identified describing a total of 787 patients. These studies are
      methodologically but not statistically heterogenous (I2 = 31%). Using a random
      effects model, the presence of contractile reserve was associated with
      significantly lower risk of mortality and cardiovascular events odds ratios of
      0.20 (CI 0.11, 0.39) ( p <0.00001) and 0.13 (CI 0.04, 0.40) (p = 0.0004)
      respectively. CONCLUSION: Regardless of stressor and imaging modality and despite
      the significant methodological heterogeneity within the current data (imaging
      techniques and parameters), patients with non-ischaemic cardiomyopathy and
      reduced EF who demonstrate contractile reserve have a lower mortality, and lower
      events / hospitalisations. The presence of contractile reserve therefore offers a
      potential positive prognostic indicator when managing these patients.

PMID- 29203461
TI  - Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models
      of Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancers (TNBC) are genetically characterized by
      aberrations in TP53 and a low rate of activating point mutations in common
      oncogenes, rendering it challenging in applying targeted therapies. We performed
      whole-exome sequencing (WES) and RNA sequencing (RNA-seq) to identify somatic
      genetic alterations in mouse models of TNBCs driven by loss of Trp53 alone or in
      combination with Brca1 Amplifications or translocations that resulted in elevated
      oncoprotein expression or oncoprotein-containing fusions, respectively, as well
      as frameshift mutations of tumor suppressors were identified in approximately 50%
      of the tumors evaluated. Although the spectrum of sporadic genetic alterations
      was diverse, the majority had in common the ability to activate the MAPK/PI3K
      pathways. Importantly, we demonstrated that approved or experimental drugs
      efficiently induce tumor regression specifically in tumors harboring somatic
      aberrations of the drug target. Our study suggests that the combination of WES
      and RNA-seq on human TNBC will lead to the identification of actionable
      therapeutic targets for precision medicine-guided TNBC treatment.Significance:
      Using combined WES and RNA-seq analyses, we identified sporadic oncogenic events
      in TNBC mouse models that share the capacity to activate the MAPK and/or PI3K
      pathways. Our data support a treatment tailored to the genetics of individual
      tumors that parallels the approaches being investigated in the ongoing NCI-MATCH,
      My Pathway Trial, and ESMART clinical trials. Cancer Discov; 8(3); 354-69.
      (c)2017 AACR.See related commentary by Natrajan et al., p. 272See related article
      by Matissek et al., p. 336This article is highlighted in the In This Issue
      feature, p. 253.

PMID- 29203464
TI  - Undernutrition and severe acute malnutrition in children.

PMID- 29203465
TI  - Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic
      review, network meta-analysis, and cost effectiveness analysis.

PMID- 29203466
TI  - Visa problems mean NHS is losing UK trained GPs, doctors warn.

PMID- 29203467
TI  - Margaret McCartney: If this was cancer there'd be an outcry-but it's mental
      health.

PMID- 29203468
TI  - EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of
      endocrine disrupters.
AB  - Human semen quality is declining in many parts of the world, but the causes are
      ill defined. In rodents, impaired sperm production can be seen with early life
      exposure to certain endocrine-disrupting chemicals, but the effects of combined
      exposures are not properly investigated. In this study, we examined the effects
      of early exposure to the painkiller paracetamol and mixtures of human relevant
      endocrine-disrupting chemicals in rats. One mixture contained four estrogenic
      compounds; another contained eight anti-androgenic environmental chemicals and a
      third mixture contained estrogens, anti-androgens and paracetamol. All exposures
      were administered by oral gavage to time-mated Wistar dams rats (n = 16-20)
      throughout gestation and lactation. In the postnatal period, testicular histology
      was affected by the total mixture, and at the end of weaning, male testis weights
      were significantly increased by paracetamol and the high doses of the total and
      the anti-androgenic mixture, compared to controls. In all dose groups, epididymal
      sperm counts were reduced several months after end of exposure, i.e. at 10 months
      of age. Interestingly, the same pattern of effects was seen for paracetamol as
      for mixtures with diverse modes of action. Reduced sperm count was seen at a dose
      level reflecting human therapeutic exposure to paracetamol. Environmental
      chemical mixtures affected sperm count at the lowest mixture dose indicating an
      insufficient margin of safety for the most exposed humans. This causes concern
      for exposure of pregnant women to paracetamol as well as environmental endocrine
      disrupters.

PMID- 29203469
TI  - Scottish GPs back new contract making them "expert medical generalists".

PMID- 29203470
TI  - Quality and Outcomes Framework could be a unique new national information
      resource.

PMID- 29203471
TI  - Primary care: how can you judge value without measuring outcomes?

PMID- 29203472
TI  - Cellular Concentrations of the Transporters DctA and DcuB and the Sensor DcuS of
      Escherichia coli and the Contributions of Free and Complexed DcuS to
      Transcriptional Regulation by DcuR.
AB  - In Escherichia coli, the catabolism of C4-dicarboxylates is regulated by the DcuS
      DcuR two-component system. The functional state of the sensor kinase DcuS is
      controlled by C4-dicarboxylates (like fumarate) and complexation with the C4
      dicarboxylate transporters DctA and DcuB, respectively. Free DcuS (DcuSF) is
      known to be constantly active even in the absence of fumarate, whereas the DcuB
      DcuS and DctA-DcuS complexes require fumarate for activation. To elucidate the
      impact of the transporters on the functional state of DcuS and the concentrations
      of DcuSF and DcuB-DcuS (or DctA-DcuS), the absolute levels of DcuS, DcuB, and
      DctA were determined in aerobically or anaerobically grown cells by mass
      spectrometry. DcuS was present at a constant very low level (10 to 20 molecules
      DcuS/cell), whereas the levels of DcuB and DctA were higher (minimum, 200
      molecules/cell) and further increased with fumarate (12.7- and 2.7-fold,
      respectively). Relating DcuS and DcuB contents with the functional state of DcuS
      allowed an estimation of the proportions of DcuS in the free (DcuSF) and the
      complexed (DcuB-DcuS) states. Unexpectedly, DcuSF levels were always low (<2% of
      total DcuS), ruling out earlier models that show DcuSF as the major species under
      noninducing conditions. In the absence of fumarate, when DcuSF is responsible for
      basal dcuB expression, up to 8% of the maximal DcuB levels are formed. These
      suffice for DcuB-DcuS complex formation and basal transport activity. In the
      presence of fumarate (>100 MUM), the DcuB-DcuS complex drives the majority of
      dcuB expression and is thus responsible for induction.IMPORTANCE Two-component
      systems (TCS) are major devices for sensing by bacteria and adaptation to
      environmental cues. Membrane-bound sensor kinases of TCS often use accessory
      proteins of unknown function. The DcuS-DcuR TCS responds to C4-dicarboxylates and
      requires formation of the complex of DcuS with C4-dicarboxylate transporters DctA
      or DcuB. Free DcuS (DcuSF) is constitutively active in autophosphorylation and
      was supposed to have a major role under specific conditions. Here, absolute
      concentrations of DcuS, DcuB, and DctA were determined under activating and
      nonactivating conditions by mass spectrometry. The relationship of their absolute
      contents to the functional state of DcuS revealed their contribution to the
      control of DcuS-DcuR in vivo, which was not accessible by other approaches,
      leading to a revision of previous models.

PMID- 29203473
TI  - Perioperative THR-184 and AKI after Cardiac Surgery.
AB  - AKI after cardiac surgery is associated with mortality, prolonged hospital length
      of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR
      184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI
      after cardiac surgery. We conducted a randomized, double-blind, placebo
      controlled, multidose comparison of the safety and efficacy of perioperative THR
      184 using a two-stage seamless adaptive design in 452 patients between 18 and 85
      years of age who were scheduled for nonemergent cardiac surgery requiring
      cardiopulmonary bypass and had recognized risk factors for AKI. The primary
      efficacy end point was the proportion of patients who developed AKI according to
      Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of
      patients who developed AKI within 7 days of surgery was similar in THR-184
      treatment groups and placebo groups (range, 74%-79%; P=0.43). Prespecified
      secondary end point analysis did not show significant differences in the severity
      of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of
      death, dialysis, or sustained impaired renal function by day 30 after surgery did
      not differ between groups (range, 11%-20%; P=0.46). Safety-related outcomes were
      similar across all treatment groups. In conclusion, compared with placebo,
      administration of perioperative THR-184 through a range of dose exposures failed
      to reduce the incidence, severity, or duration of AKI after cardiac surgery in
      high-risk patients.

PMID- 29203474
TI  - Skyline Performs as Well as Vendor Software in the Quantitative Analysis of Serum
      25-Hydroxy Vitamin D and Vitamin D Binding Globulin.

PMID- 29203475
TI  - HDL Particle Measurement: Comparison of 5 Methods.
AB  - BACKGROUND: HDL cell cholesterol efflux capacity has been documented as superior
      to HDL cholesterol (HDL-C) in predicting cardiovascular disease risk. HDL
      functions relate to its composition. Compositional assays are easier to perform
      and standardize than functional tests and are more practical for routine testing.
      Our goal was to compare measurements of HDL particles by 5 different separation
      methods. METHODS: HDL subfractions were measured in 98 samples using vertical
      auto profiling (VAP), ion mobility (IM), nuclear magnetic resonance (NMR), native
      2-dimensional gel electrophoresis (2D-PAGE), and pre-beta1-ELISA. VAP measured
      cholesterol in large HDL2 and small HDL3; IM measured particle number directly in
      large, intermediate, and small HDL particles; NMR measured lipid signals in
      large, medium, and small HDL; 2D-PAGE measured apolipoprotein (apo) A-I in large
      (alpha1), medium (alpha2), small (alpha3-4), and pre-beta1 HDL particles; and
      ELISA measured apoA-I in pre-beta1-HDL. The data were normalized and compared
      using Passing-Bablok, Lin concordance, and Bland-Altman plot analyses. RESULTS:
      With decreasing HDL-C concentration, NMR measured a gradually lower percentage of
      large HDL, compared with IM, VAP, and 2D-PAGE. In the lowest HDL-C tertile, NMR
      measured 8% of large HDL, compared with IM, 22%; VAP, 20%; and 2D-PAGE, 18%.
      There was strong discordance between 2D-PAGE and NMR in measuring medium HDL (R2
      = 0.356; rc = 0.042) and small HDL (R2 = 0.376; rc = 0.040). The 2D-PAGE assay
      measured a significantly higher apoA-I concentration in pre-beta1-HDL than the
      pre-beta1-ELISA (9.8 vs 1.6 mg/dL; R2 = 0.246; rc = 0.130). CONCLUSIONS: NMR
      agreed poorly with the other methods in measuring large HDL, particularly in low
      HDL-C individuals. Similarly, there was strong discordance in pre-beta1-HDL
      measurements between the ELISA and 2D-PAGE assays.

PMID- 29203477
TI  - PnuT uses a facilitated diffusion mechanism for thiamine uptake.
AB  - Membrane transporters of the bacterial pyridine nucleotide uptake (Pnu) family
      mediate the uptake of various B-type vitamins. For example, the PnuT transporters
      have specificity for vitamin B1 (thiamine). It has been hypothesized that Pnu
      transporters are facilitators that allow passive transport of the vitamin
      substrate across the membrane. Metabolic trapping by phosphorylation would then
      lead to accumulation of the transported substrates in the cytoplasm. However,
      experimental evidence for such a transport mechanism is lacking. Here, to
      determine the mechanism of thiamine transport, we purify PnuTSw from Shewanella
      woodyi and reconstitute it in liposomes to determine substrate binding and
      transport properties. We show that the electrochemical gradient of thiamine
      solely determines the direction of transport, consistent with a facilitated
      diffusion mechanism. Further, PnuTSw can bind and transport thiamine as well as
      the thiamine analogues pyrithiamine and oxythiamine, but does not recognize the
      phosphorylated derivatives thiamine monophosphate and thiamine pyrophosphate as
      substrates, consistent with a metabolic trapping mechanism. Guided by the crystal
      structure of the homologous nicotinamide riboside transporter PnuC, we perform
      mutagenesis experiments, which reveal residues involved in substrate binding and
      gating. The facilitated diffusion mechanism of transport used by PnuTSw contrasts
      sharply with the active transport mechanisms used by other bacterial thiamine
      transporters.

PMID- 29203476
TI  - UCP1 deficiency increases adipose tissue monounsaturated fatty acid synthesis and
      trafficking to the liver.
AB  - Uncoupling protein-1 (UCP1) facilitates thermogenesis in brown and beige
      adipocytes and can promote energy expenditure by decreasing mitochondrial
      respiratory efficiency. Defects in UCP1 and brown adipose tissue thermogenesis
      subject animals to chronic cold stress and elicit compensatory responses to
      generate heat. How UCP1 regulates white adipose tissue (WAT) lipid biology and
      tissue crosstalk is not completely understood. Here, we probed the effect of UCP1
      deficiency on FA metabolism in inguinal and epididymal WAT and investigated how
      these metabolic perturbations influence hepatic lipid homeostasis. We report that
      at standard housing temperature (21 degrees C), loss of UCP1 induces inguinal WAT
      de novo lipogenesis through transcriptional activation of the lipogenic gene
      program and elevated GLUT4. Inguinal adipocyte hyperplasia and depot expansion
      accompany the increase in lipid synthesis. We also found that UCP1 deficiency
      elevates adipose stearoyl-CoA desaturase gene expression, and increased inguinal
      WAT lipolysis supports the transport of adipose-derived palmitoleate (16:1n7) to
      the liver and hepatic triglyceride accumulation. The observed WAT and liver
      phenotypes were resolved by housing animals at thermoneutral housing (30 degrees
      C). These data illustrate depot-specific responses to impaired BAT thermogenesis
      and communication between WAT and liver in UCP1-/- mice.

PMID- 29203478
TI  - Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin
      Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis.
AB  - Recent data conflict on the clinical efficacy of later-generation
      fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of
      multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but
      susceptible to moxifloxacin. The purpose of the present study was to evaluate
      whether later-generation fluoroquinolones can improve treatment outcomes in
      patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A
      retrospective cohort study was performed on 208 patients with moxifloxacin
      susceptible MDR-TB who were treated between 2006 and 2011. Later-generation
      fluoroquinolones were used for all patients. Overall, 171 patients (82%) had
      ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible
      group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB
      (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the
      ofloxacin-resistant group was more likely to have a history of MDR-TB treatment
      (P < 0.001) and cavitary lesions on chest radiography (P < 0.001). In addition,
      the ofloxacin-resistant group was more likely than the ofloxacin-susceptible
      group to have resistance to the drugs pyrazinamide (P = 0.003), streptomycin (P =
      0.015), prothionamide (P < 0.001), and para-aminosalicylic acid (P < 0.001).
      Favorable outcomes were more frequently achieved for the ofloxacin-susceptible
      group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37],
      respectively [P < 0.001]). In multivariable regression logistic analysis, the
      ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to
      18.53) times more likely than the ofloxacin-resistant group (P < 0.001) to have
      favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency
      of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly
      lower than that for ofloxacin-susceptible MDR-TB, even when later-generation
      fluoroquinolones were used, indicating that more-aggressive therapies may be
      needed for ofloxacin-resistant MDR-TB.

PMID- 29203479
TI  - Host-Pathogen-Treatment Triad: Host Factors Matter Most in Methicillin-Resistant
      Staphylococcus aureus Bacteremia Outcomes.
AB  - Previous studies have separately emphasized the importance of host, pathogen, and
      treatment characteristics in determining short-term or in-hospital mortality
      rates for patients with methicillin-resistant Staphylococcus aureus (MRSA)
      bloodstream infections. Less is known about the relative importance of these
      factors and their interactions in determining short-, medium-, and long-term
      mortality rates. This is an observational cohort study in which data for all
      patients admitted to the University of New Mexico (UNM) Health Sciences Center
      (HSC) between July 2002 and August 2013 with MRSA-positive blood cultures were
      recorded. We collected patients' demographics and treatment data, as well as data
      on genetic markers of the MRSA isolates. Outcomes of interest were determinants
      of short-term (within 30 days), medium-term (30 to 90 days), and long-term (>90
      days) mortality rates. This study included 273 patients with MRSA bacteremia.
      Short-, medium-, and long-term mortality rates were 18.7%, 26.4%, and 48%,
      respectively. Thirty-day mortality rates were influenced by host variables and
      host-pathogen interaction characteristics. Pitt bacteremia scores, malignancy,
      and health care exposure contributed to 30- to 90-day mortality rates, while
      treatment duration of >4 weeks had a protective effect. Age remained a
      significant risk factor for death at >90 days, while admission leukocytosis was
      protective. Infection represented the most frequent cause of death for all three
      time frames; rates varied from 72.6% in the first 30 days and 60% for 30 to 90
      days to 35.7% for >90 days (P = 0.003). Host characteristics affect short-,
      medium-, and long-term mortality rates for MRSA bloodstream infections more than
      do pathogen genetic markers and treatment factors.

PMID- 29203480
TI  - Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive
      Candidiasis Murine Model Using an Extended-Interval Dosing Design.
AB  - Echinocandins are important in the prevention and treatment of invasive
      candidiasis but limited by current dosing regimens that include daily intravenous
      administration. The novel echinocandin CD101 has a prolonged half-life of
      approximately 130 h in humans, making it possible to design once-weekly dosing
      strategies. The present study examined the pharmacodynamic activity of CD101
      using the neutropenic invasive candidiasis mouse model against select Candida
      albicans (n = 4), C. glabrata (n = 3), and C. parapsilosis (n = 3) strains. The
      CD101 MIC ranged from 0.03 to 1 mg/liter. Plasma pharmacokinetic measurements
      were performed using uninfected mice after intraperitoneal administration of 1,
      4, 16, and 64 mg/kg. The elimination half-life was prolonged at 28 to 41 h.
      Neutropenic mice were infected with each strain by lateral tail vein injection,
      treated with a single dose of CD101, and monitored for 7 days, at which time the
      organism burden was enumerated from the kidneys. Dose-dependent activity was
      observed for each organism. The pharmacokinetic/pharmacodynamic (PK/PD) index of
      the area under the concentration-time curve over 24 h in the steady state divided
      by the MIC (AUC/MIC index) correlated well with efficacy (R2, 0.74 to 0.93). The
      median stasis 24-h free-drug AUC/MIC targets were as follows: for C. albicans,
      2.92; for C. glabrata, 0.07; and for C. parapsilosis, 2.61. The PK/PD targets for
      1-log10 kill endpoint were 2- to 4-fold higher. Interestingly, the aforementioned
      PK/PD targets of CD101 were numerically lower for all three species than those of
      other echinocandins. In summary, CD101 is a promising, novel echinocandin with
      advantageous pharmacokinetic properties and potent in vivo pharmacodynamic
      activity.

PMID- 29203482
TI  - Presence of an mcr-3 Variant in Aeromonas caviae, Proteus mirabilis, and
      Escherichia coli from One Domestic Duck.

PMID- 29203481
TI  - Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients.
AB  - Effective concentrations of antibiotics in brain tissue are essential for
      antimicrobial therapy of brain infections. However, data concerning cerebral
      penetration properties of antibiotics for treatment or prophylaxis of central
      nervous system infections are rare. Six patients suffering subarachnoid
      hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were
      included in this study. Free interstitial concentrations of cefuroxime after
      intravenous application of 1,500 mg were measured by microdialysis in brain
      tissue, as well as in plasma at steady-state (n = 6) or after single-dose
      administration (n = 1). At steady state, free area under the concentration-time
      curve from 0 to 24 h (AUC0-24) values of 389.0 +/- 210.3 mg/liter.h and 131.4 +/-
      72.8 mg/liter.h were achieved for plasma and brain, respectively, resulting in a
      brain tissue penetration ratio (AUC0-24 brain/AUC0-24 free plasma) of 0.33 +/-
      0.1. Plasma and brain tissue concentrations at individual time points correlated
      well (R = 0.59, P = 0.001). At steady-state time over MIC (t>MIC) values of >40%
      of dosing interval were achieved up to an MIC of 16 mg/liter for plasma and 4
      mg/liter for brain tissue. Although MIC90 values could not be achieved in brain
      tissue for relevant bacteria, current dosing strategies of cefuroxime might be
      sufficient to treat pathogens with MIC values up to 4 mg/liter. The activity of
      cefuroxime in brain tissue might be overestimated when relying exclusively on
      plasma levels. Although currently insufficient data after single dose
      administration exist, lower brain-plasma ratios observed after the first dose
      might warrant a loading dose for treatment and perioperative prophylaxis.

PMID- 29203483
TI  - Intermittent Antibiotic Therapy for Recurrent Nodular Bronchiectatic
      Mycobacterium avium Complex Lung Disease.
AB  - Intermittent, three-times-weekly oral antibiotic therapy is recommended for the
      initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium
      complex (MAC) lung disease. However, intermittent therapy is not recommended for
      patients who have been previously treated. We evaluated 53 patients with
      recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for
      >=12 months with daily therapy (n = 26) or intermittent therapy (n = 27) between
      January 2008 and December 2015. Baseline characteristics were comparable between
      daily therapy and intermittent therapy groups. Sputum culture conversion rates
      did not differ between daily therapy (21/26, 81%) and intermittent therapy
      (22/27, 82%) groups. Compared to the etiologic organism at the time of previous
      treatment, recurrent MAC lung disease was caused by the same MAC species in 38
      patients (72%) and by a different MAC species in 15 patients (28%). Genotype
      analysis in patients with sequenced paired isolates revealed that 86% (12/14) of
      cases with same species recurrence were due to reinfection with a new MAC
      genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases
      were caused by reinfection rather than relapse. Intermittent antibiotic therapy
      is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.

PMID- 29203484
TI  - Novel Treatment of Staphylococcus aureus Device-Related Infections Using
      Fibrinolytic Agents.
AB  - Staphylococcal infections involving biofilms represent a significant challenge in
      the treatment of patients with device-related infections. Staphylococcus aureus
      biofilms have been shown to be SaeRS regulated and dependent on the coagulase
      catalyzed conversion of fibrinogen into fibrin on surfaces coated with human
      plasma. Here we investigated the treatment of staphylococcal biofilm device
      related infections by digesting the fibrin biofilm matrix with and without
      existing antimicrobials. The fibrinolytic agents plasmin, streptokinase, and
      nattokinase, and TrypLE, a recombinant trypsin-like protease, were used to digest
      and treat S. aureus biofilms grown in vitro using in vivo-like static biofilm
      assays with and without antimicrobials. Cytotoxicity, the potential to induce a
      cytokine response in whole human blood, and the risk of induction of tolerance to
      fibrinolytic agents were investigated. A rat model of intravascular catheter
      infection was established to investigate the efficacy of selected fibrinolytic
      agents in vivo Under biomimetic conditions, the fibrinolytic agents effectively
      dispersed established S. aureus biofilms and, in combination with common
      antistaphylococcal antimicrobials, effectively killed bacterial cells being
      released from the biofilm. These fibrinolytic agents were not cytotoxic and did
      not affect the host immune response. The rat model of infection successfully
      demonstrated the activity of the selected fibrinolytic agents alone and in
      combination with antimicrobials on established biofilms in vivo TrypLE and
      nattokinase most successfully removed adherent cells from plasma-coated surfaces
      and significantly improved the efficacy of existing antimicrobials against S.
      aureus biofilms in vitro and in vivo These biofilm dispersal agents represent a
      viable future treatment option for S. aureus device-related infections.

PMID- 29203485
TI  - In Vitro and In Vivo Studies of the Trypanocidal Effect of Novel Quinolines.
AB  - Therapies for human African trypanosomiasis and Chagas disease, caused by
      Trypanosoma brucei and Trypanosoma cruzi, respectively, are limited, providing
      minimal therapeutic options for the millions of individuals living in very poor
      communities. Here the effects of 10 novel quinolines are evaluated in silico and
      by phenotypic studies using in vitro and in vivo models. Absorption,
      distribution, metabolism, excretion, and toxicity (ADMET) properties revealed
      that most molecules did not infringe on Lipinski's rules, which is a prediction
      of good oral absorption. These quinolines showed high probabilities of Caco2
      permeability and human intestinal absorption and low probabilities of
      mutagenicity and of hERG1 inhibition. In vitro screens against bloodstream forms
      of T. cruzi demonstrated that all quinolines were more active than the reference
      drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187,
      DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations
      (EC50s) of <3 MUM (4-fold lower than that of Bz). Nine quinolines were more
      effective than Bz (2.7 MUM) against amastigotes, showing EC50s ranging from 0.6
      to 0.1 MUM. All quinolines were also highly active in vitro against African
      trypanosomes, showing EC50s of <=0.25 MUM. The most potent and highly selective
      candidates for each parasite species were tested in in vivo models. Results for
      DB2186 were promising in mice with T. cruzi and T. brucei infections, reaching a
      70% reduction of the parasitemia load for T. cruzi, and it cured 2 out of 4 mice
      infected with T. brucei DB2217 was also active in vivo and cured all 4 mice (100%
      cure rate) with T. brucei infection.

PMID- 29203486
TI  - In Vitro, In Silico, and In Vivo Analyses of Novel Aromatic Amidines against
      Trypanosoma cruzi.
AB  - Five bis-arylimidamides were assayed as anti-Trypanosoma cruzi agents by in
      vitro, in silico, and in vivo approaches. None were considered to be pan-assay
      interference compounds. They had a favorable pharmacokinetic landscape and were
      active against trypomastigotes and intracellular forms, and in combination with
      benznidazole, they gave no interaction. The most selective agent (28SMB032)
      tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5
      days intraperitoneally) but without mortality protection. In silico target
      fishing suggested DNA as the main target, but ultrastructural data did not match.

PMID- 29203487
TI  - Role of smeU1VWU2X Operon in Alleviation of Oxidative Stresses and Occurrence of
      Sulfamethoxazole-Trimethoprim-Resistant Mutants in Stenotrophomonas maltophilia.
AB  - Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an
      important mechanism for bacteria to combat antimicrobials. RND efflux pumps are
      also critical for bacterial physiology, such as oxidative stress tolerance.
      Stenotrophomonas maltophilia, a multidrug-resistant opportunistic pathogen,
      harbors eight RND-type efflux pump operons. Of these, the smeU1VWU2X operon is
      unique for its possession of two additional genes, smeU1 and smeU2, which encode
      proteins of the short-chain dehydrogenase/reductase (SDR) family. Overexpression
      of the SmeVWX pump is known to contribute to the acquired resistance to
      chloramphenicol, quinolone, and tetracycline; however, SmeU1 and SmeU2 are little
      involved in this phenotype. In the study described in this article, we further
      linked the smeU1VWU2X operon to oxidative stress alleviation and sulfamethoxazole
      trimethoprim (SXT)-resistant mutant occurrence. The smeU1VWU2X operon was
      inducibly expressed upon challenge with menadione (MD), plumbagin (PL), and
      hydrogen peroxide (H2O2), as verified by the use of the chromosomal smeU1VWU2X
      xylE transcriptional fusion construct and quantitative real-time PCR (qRT-PCR).
      The MD-mediated smeU1VWU2X upexpression was totally dependent on SoxR and
      partially relied on SmeRv but was less relevant to OxyR. SmeRv, but not SoxR and
      OxyR, played a regulatory role in the H2O2-mediated smeU1VWU2X upexpression. The
      significance of smeU1VWU2X upexpression was investigated with respect to
      oxidative stress alleviation and SXT-resistant mutant occurrence. Overexpression
      of the smeU1VWU2X operon contributed to the alleviation of MD-mediated oxidative
      stress. Of the encoded proteins, the SmeVWX pump and SmeU2, rather than SmeU1,
      participated in MD tolerance. Furthermore, we also demonstrated that the MD
      mediated expression of the smeU1VWU2X operon decreased the SXT resistance
      frequency when S. maltophilia was grown in a reactive oxygen species (ROS)-rich
      environment.

PMID- 29203488
TI  - Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from
      the China CRE Network.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in
      China, but estimates of the infection burden are lacking. We established the
      incidence of CRE infection from a multicenter study that covered 25 tertiary
      hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible
      Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella
      pneumoniae infections during January to December 2015 were collected and reviewed
      from medical records. Antimicrobial susceptibility testing and carbapenemase gene
      identification were performed. Among 664 CRE cases, most were caused by K.
      pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The
      overall CRE infection incidence per 10,000 discharges was 4.0 and differed
      significantly by region, with the highest in Jiangsu (14.97) and the lowest in
      Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the
      median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients
      were male. Lower respiratory tract infections (65.4%) were the most common,
      followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%),
      and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All
      isolates showed nonsusceptibility to carbapenems and cephalosporins. The
      susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher
      susceptibility rate against E. coli than against K. pneumoniae (90.9% versus
      40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a
      majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases
      among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0
      per 10,000 discharges. The patient-based disease burden in tertiary hospitals in
      China is severe, suggesting an urgent need to enhance infection control.

PMID- 29203489
TI  - Distribution and Molecular Characterization of Acinetobacter baumannii
      International Clone II Lineage in Japan.
AB  - Multidrug-resistant (MDR) Acinetobacter spp. have been globally disseminated in
      association with the successful clonal lineage Acinetobacter baumannii
      international clone II (IC II). Because the prevalence of MDR Acinetobacter spp.
      in Japan remains very low, we characterized all Acinetobacter spp. (n = 866) from
      76 hospitals between October 2012 and March 2013 to describe the entire molecular
      epidemiology of Acinetobacter spp. The most prevalent species was A. baumannii (n
      = 645; 74.5%), with A. baumannii IC II (n = 245) accounting for 28.3% of the
      total. Meropenem-resistant isolates accounted for 2.0% (n = 17) and carried
      ISAba1-blaOXA-23-like (n = 10), blaIMP (n = 4), or ISAba1-blaOXA-51-like (n = 3).
      Multilocus sequence typing of 110 representative A. baumannii isolates revealed
      the considerable prevalence of domestic sequence types (STs). A. baumannii IC II
      isolates were divided into the domestic sequence type 469 (ST469) (n = 18) and
      the globally disseminated STs ST208 (n = 14) and ST219 (n = 4). ST469 isolates
      were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced
      the intrinsic AmpC beta-lactamase. A. baumannii IC II and some A. baumannii non
      IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone
      resistance. This study revealed that carbapenem-susceptible A. baumannii IC II
      was moderately disseminated in Japan. The low prevalence of acquired
      carbapenemase genes and presence of domestic STs could contribute to the low
      prevalence of MDR A. baumannii A similar epidemiology might have appeared before
      the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone
      resistance associated with A. baumannii IC II may provide insight into the
      significance of A. baumannii epidemic clones.

PMID- 29203490
TI  - Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a
      Role in beta-Lactam Resistance in Helicobacter cinaedi.
AB  - beta-Lactams are often used to treat Helicobacter cinaedi infections; however,
      the mechanism underlying beta-lactam resistance is unknown. In this study, we
      investigated beta-lactam resistance in an H. cinaedi strain, MRY12-0051 (MICs of
      amoxicillin [AMX] and ceftriaxone [CRO], 32 and 128 MUg/ml; obtained from human
      feces). Based on a comparative whole-genome analysis of MRY12-0051 and the CRO
      susceptible H. cinaedi strain MRY08-1234 (MICs of AMX and CRO, 1 and 4 MUg/ml;
      obtained from human blood), we identified five mutations in genes encoding
      penicillin-binding proteins (PBPs), including two in pbpA, one in pbp2, and two
      in ftsI Transformation and penicillin binding assays indicated that CRO
      resistance was mainly associated with mutations in pbpA; mutations in ftsI also
      led to increased resistance to AMX. Knocking out cmeB and cmeD, which encode
      resistance-nodulation-division-type efflux pump components, in H. cinaedi type
      strain CCUG18818 (AMX MIC, 4 to 8 MUg/ml) resulted in 8- and 64-fold decreases,
      respectively, in the AMX MIC. Hence, MICs of AMX in H. cinaedi become similar to
      those of Helicobacter pylori isolates in the absence of cmeD In conclusion, the
      difference in susceptibility to beta-lactams between H. pylori and H. cinaedi is
      explained by differences in efflux pump components. Mutations in pbpA are the
      primary determinant of high resistance to beta-lactams in H. cinaedi.

PMID- 29203491
TI  - Chemogenomic Profiling of the Fungal Pathogen Candida albicans.
AB  - There is currently a small number of classes of antifungal drugs, and these drugs
      are known to target a very limited set of cellular functions. We derived a set of
      approximately 900 nonessential, transactivator-defective disruption strains from
      the tetracycline-regulated GRACE collection of strains of the fungal pathogen
      Candida albicans This strain set was screened against classic antifungal drugs to
      identify gene inactivations that conferred either enhanced sensitivity or
      increased resistance to the compounds. We examined two azoles, fluconazole and
      posaconazole; two echinocandins, caspofungin and anidulafungin; and a polyene,
      amphotericin B. Overall, the chemogenomic profiles within drug classes were
      highly similar, but there was little overlap between classes, suggesting that the
      different drug classes interacted with discrete networks of genes in C. albicans
      We also tested two pyridine amides, designated GPI-LY7 and GPI-C107; these drugs
      gave very similar profiles that were distinct from those of the echinocandins,
      azoles, or polyenes, supporting the idea that they target a distinct cellular
      function. Intriguingly, in cases where these gene sets can be compared to genetic
      disruptions conferring drug sensitivity in other fungi, we find very little
      correspondence in genes. Thus, even though the drug targets are the same in the
      different species, the specific genetic profiles that can lead to drug
      sensitivity are distinct. This implies that chemogenomic screens of one organism
      may be poorly predictive of the profiles found in other organisms and that drug
      sensitivity and resistance profiles can differ significantly among organisms even
      when the apparent target of the drug is the same.

PMID- 29203492
TI  - Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum.
AB  - Tuberculosis (TB) recently became the leading infectious cause of death in
      adults, while attempts to shorten therapy have largely failed. Dormancy,
      persistence, and drug tolerance are among the factors driving the long therapy
      duration. Assays to measure in situ drug susceptibility of Mycobacterium
      tuberculosis bacteria in pulmonary lesions are needed if we are to discover new
      fast-acting regimens and address the global TB threat. Here we take a first step
      toward this goal and describe an ex vivo assay developed to measure the cidal
      activity of anti-TB drugs against M. tuberculosis bacilli present in cavity
      caseum obtained from rabbits with active TB. We show that caseum M. tuberculosis
      bacilli are largely nonreplicating, maintain viability over the course of the
      assay, and exhibit extreme tolerance to many first- and second-line TB drugs.
      Among the drugs tested, only the rifamycins fully sterilized caseum. A similar
      trend of phenotypic drug resistance was observed in the hypoxia- and starvation
      induced nonreplicating models, but with notable qualitative and quantitative
      differences: (i) caseum M. tuberculosis exhibits higher drug tolerance than
      nonreplicating M. tuberculosis in the Wayne and Loebel models, and (ii)
      pyrazinamide is cidal in caseum but has no detectable activity in these classic
      nonreplicating assays. Thus, ex vivo caseum constitutes a unique tool to evaluate
      drug potency against slowly replicating or nonreplicating bacilli in their native
      caseous environment. Intracaseum cidal concentrations can now be related to the
      concentrations achieved in the necrotic foci of granulomas and cavities to
      establish correlations between clinical outcome and lesion-centered
      pharmacokinetics-pharmacodynamics (PK-PD) parameters.

PMID- 29203493
TI  - Prospective Trial on the Use of Trough Concentration versus Area under the Curve
      To Determine Therapeutic Vancomycin Dosing.
AB  - We hypothesized that dosing vancomycin to achieve trough concentrations of >15
      mg/liter overdoses many adults compared to area under the concentration-time
      curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin
      dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians
      targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and
      controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing
      with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of
      >=400, with a maximum AUC value of 800 mg . h/liter, regardless of trough
      concentration. For Bayesian estimation of AUCs, we used trough samples in years 1
      and 2 and optimally timed samples in year 3. We enrolled 252 adults who were >=18
      years old with >=1 available vancomycin concentration. Only 19% of all trough
      concentrations were therapeutic versus 70% of AUCs (P < 0.0001). After
      enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9
      mg/liter (P = 0.005), with 36%, 7%, and 6% over 15 mg/liter (P < 0.0001).
      Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional
      blood samples per subject (3.6, 2.0, and 2.4; P = 0.003), shorter therapy
      durations (8.2, 5.4, and 4.7 days; P = 0.03), and reduced nephrotoxicity (8%, 0%,
      and 2%; P = 0.01). The median inpatient stay was 20 days among nephrotoxic
      patients versus 6 days (P = 0.002). There was no difference in efficacy by year,
      with 42% of patients having microbiologically proven infections. Compared to
      trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin
      dosing was associated with decreased nephrotoxicity, reduced per-patient blood
      sampling, and shorter length of therapy, without compromising efficacy. These
      benefits have the potential for substantial cost savings. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT01932034.).

PMID- 29203494
TI  - Evaluation of Activity and Emergence of Resistance of Polymyxin B and ZTI-01
      (Fosfomycin for Injection) against KPC-Producing Klebsiella pneumoniae.
AB  - ZTI-01 (fosfomycin for injection) is a broad-spectrum antibiotic with a novel
      mechanism of action and is currently under development in the United States for
      treatment of complicated urinary tract infections. Globally, fosfomycin and
      polymyxin B are increasingly being used to treat multidrug-resistant Gram
      negative infections. The objectives were to evaluate the pharmacodynamic activity
      of polymyxin B and fosfomycin alone and in combination against KPC-producing
      Klebsiella pneumoniae and to assess the rate and extent of emergence of
      resistance to different antibiotic regimens. Two clinical isolates, BRKP26 (MIC
      of polymyxin B[MICPMB], 0.5 mg/liter; MIC of fosfomycin [MICFOF], 32 mg/liter)
      and BRKP67 (MICPMB, 8 mg/liter; MICFOF, 32 mg/liter) at an initial inoculum of
      107 CFU/ml, were evaluated over 168 h in a hollow-fiber infection model
      simulating clinically relevant polymyxin B (2.5-mg/kg loading dose as a 2 h
      infusion followed by 1.5-mg/kg dose every 12 h [q12h] as a 1-h infusion) and
      fosfomycin (6 g q6h as a 1-h or 3-h infusion) regimens alone and in combination.
      Population analysis profiles (PAPs) and MIC testing were performed to assess
      emergence of resistance. Polymyxin B or fosfomycin monotherapy was ineffective
      and selected for resistance by 24 h. Polymyxin B plus a fosfomycin 1-h infusion
      demonstrated sustained bactericidal activity by 4 h, with undetectable colony
      counts beyond 144 h. Polymyxin B plus a fosfomycin 3-h infusion demonstrated
      bactericidal activity at 4 h, followed by regrowth similar to that of the control
      by 144 h. PAPs revealed resistant subpopulations by 120 h. The combination of
      polymyxin B and a fosfomycin 1-h infusion is a promising treatment option for KPC
      producing K. pneumoniae and suppresses the emergence of resistance. Further
      evaluation of novel dosing strategies is warranted to optimize therapy.

PMID- 29203495
TI  - PA5470 Counteracts Antimicrobial Effect of Azithromycin by Releasing Stalled
      Ribosome in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa causes various acute and chronic infections in humans.
      Treatment with azithromycin (AZM) has been shown to benefit patients with chronic
      P. aeruginosa infections. By binding to the exit tunnel of the 50S ribosome, AZM
      causes ribosome stalling and depletion of the intracellular tRNA pool. It has
      been shown that AZM is able to kill stationary-phase P. aeruginosa cells and
      repress quorum sensing-regulated virulence factors as well as swarming motility.
      In P. aeruginosa, the PA5470 gene encodes a putative peptide chain release factor
      whose expression is highly induced by macrolide antibiotics. However, its
      function remains unknown. Here, we found that overexpression of PA5470 increased
      bacterial tolerance against AZM and alleviated the repression of swarming
      motility. Ribosome pulldown assays revealed that PA5470 contributes to the
      release of ribosome stalled by AZM. We further demonstrate that overexpression of
      PA5470 counteracts AZM-mediated repression of the translation of the quorum
      sensing regulator RhlR. Overall, our results revealed a novel role of PA5470 in
      the bacterial response to AZM.

PMID- 29203496
TI  - Extended Linkers Improve the Detection of Protein-protein Interactions (PPIs) by
      Dihydrofolate Reductase Protein-fragment Complementation Assay (DHFR PCA) in
      Living Cells.
AB  - Understanding the function of cellular systems requires describing how proteins
      assemble with each other into transient and stable complexes and to determine
      their spatial relationships. Among the tools available to perform these analyses
      on a large scale is Protein-fragment Complementation Assay based on the
      dihydrofolate reductase (DHFR PCA). Here we test how longer linkers between the
      fusion proteins and the reporter fragments affect the performance of this assay.
      We investigate the architecture of the RNA polymerases, the proteasome and the
      conserved oligomeric Golgi (COG) complexes in living cells and performed large
      scale screens with these extended linkers. We show that longer linkers
      significantly improve the detection of protein-protein interactions and allow to
      measure interactions further in space than the standard ones. We identify new
      interactions, for instance between the retromer complex and proteins related to
      autophagy and endocytosis. Longer linkers thus contribute an enhanced additional
      tool to the existing toolsets for the detection and measurements of protein
      protein interactions and protein proximity in living cells.

PMID- 29203497
TI  - Outer Membrane Vesicles (OMV)-based and Proteomics-driven Antigen Selection
      Identifies Novel Factors Contributing to Bordetella pertussis Adhesion to
      Epithelial Cells.
AB  - Despite high vaccination coverage world-wide, whooping cough, a highly contagious
      disease caused by Bordetella pertussis, is recently increasing in occurrence
      suggesting that novel vaccine formulations targeted at the prevention of
      colonization and transmission should be investigated. To identify new candidates
      for inclusion in the acellular formulation, we used spontaneously released outer
      membrane vesicles (OMV)1 as a potential source of key adhesins. The enrichment of
      Bvg+ OMV with adhesins and the ability of anti-OMV serum to inhibit the adhesion
      of B. pertussis to lung epithelial cells in vitro were demonstrated. We employed
      a proteomic approach to identify the differentially expressed proteins in OMV
      purified from bacteria in the Bvg+ and Bvg- virulence phases, thus comparing the
      outer membrane protein pattern of this pathogen in its virulent or avirulent
      state. Six of the most abundant outer membrane proteins were selected as
      candidates to be evaluated for their adhesive properties and vaccine potential.
      We generated E. coli strains singularly expressing the selected proteins and
      assessed their ability to adhere to lung epithelial cells in vitro Four out of
      the selected proteins conferred adhesive ability to E. coli Three of the
      candidates were specifically detected by anti-OMV mouse serum suggesting that
      these proteins are immunogenic antigens able to elicit an antibody response when
      displayed on the OMV. Anti-OMV serum was able to inhibit only BrkA-expressing E.
      coli adhesion to lung epithelial cells. Finally, stand-alone immunization of mice
      with recombinant BrkA resulted in significant protection against infection of the
      lower respiratory tract after challenge with B. pertussis Taken together, these
      data support the inclusion of BrkA and possibly further adhesins to the current
      acellular pertussis vaccines to improve the impact of vaccination on the
      bacterial clearance.

PMID- 29203499
TI  - Comment on 'End of the road for Essure(r)?'

PMID- 29203498
TI  - Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality,
      and Characterization.
AB  - BACKGROUND: Perioperative myocardial injury (PMI) seems to be a contributor to
      mortality after noncardiac surgery. Because the vast majority of PMIs are
      asymptomatic, PMI usually is missed in the absence of systematic screening.
      METHODS: We performed a prospective diagnostic study enrolling consecutive
      patients undergoing noncardiac surgery who had a planned postoperative stay of
      >=24 hours and were considered at increased cardiovascular risk. All patients
      received a systematic screening using serial measurements of high-sensitivity
      cardiac troponin T in clinical routine. PMI was defined as an absolute high
      sensitivity cardiac troponin T increase of >=14 ng/L from preoperative to
      postoperative measurements. Furthermore, mortality was compared among patients
      with PMI not fulfilling additional criteria (ischemic symptoms, new ECG changes,
      or imaging evidence of loss of viable myocardium) required for the diagnosis of
      spontaneous acute myocardial infarction versus those that did. RESULTS: From 2014
      to 2015 we included 2018 consecutive patients undergoing 2546 surgeries. Patients
      had a median age of 74 years and 42% were women. PMI occurred after 397 of 2546
      surgeries (16%; 95% confidence interval, 14%-17%) and was accompanied by typical
      chest pain in 24 of 397 patients (6%) and any ischemic symptoms in 72 of 397
      (18%). Crude 30-day mortality was 8.9% (95% confidence interval [CI], 5.7-12.0)
      in patients with PMI versus 1.5% (95% CI, 0.9-2.0) in patients without PMI
      (P<0.001). Multivariable regression analysis showed an adjusted hazard ratio of
      2.7 (95% CI, 1.5-4.8) for 30-day mortality. The difference was retained at 1 year
      with mortality rates of 22.5% (95% CI, 17.6-27.4) versus 9.3% (95% CI, 7.9-10.7).
      Thirty-day mortality was comparable among patients with PMI not fulfilling any
      other of the additional criteria required for spontaneous acute myocardial
      infarction (280/397, 71%) versus those with at least 1 additional criterion
      (10.4%; 95% CI, 6.7-15.7, versus 8.7%; 95% CI, 4.2-16.7; P=0.684). CONCLUSIONS:
      PMI is a common complication after noncardiac surgery and, despite early
      detection during routine clinical screening, is associated with substantial short
      and long-term mortality. Mortality seems comparable in patients with PMI not
      fulfilling any other of the additional criteria required for spontaneous acute
      myocardial infarction versus those patients who do. CLINICAL TRIAL REGISTRATION:
      URL: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.

PMID- 29203500
TI  - Two women with extended use of contraceptive implants.

PMID- 29203501
TI  - Effect of a newly designed observation, response and discharge chart in the Post
      Anaesthesia Care Unit on patient outcomes: a quasi-expermental study in
      Australia.
AB  - OBJECTIVES: This study aimed to evaluate whether use of a discharge criteria tool
      for nursing assessment of patients in Post Anaesthesia Care Unit (PACU) would
      enhance nurses' recognition and response to patients at-risk of deterioration and
      improve patient outcomes. METHODS: A prospective non-randomised pre-post
      intervention study was conducted in three hospitals in Australia. Participants
      were adults undergoing elective surgery before (n=723) and after (n=694)
      implementation of the Post-Anaesthetic Care Tool (PACT). RESULTS: Nursing
      response to patients at-risk of deterioration was higher using PACT, with more
      medical consultations initiated by PACU nurses (19% vs 30%, P<0.001) and more
      patients with Medical Emergency Team activation criteria modified by an
      anaesthetist while in PACU (6.5% vs 13.8%, P<0.001). There were higher rates of
      analgesia administration (37.3% vs 54.2%, P=0.001), nursing assessment of pain
      and documentation of ongoing analgesia prior to discharge (55% vs 85%, P<0.001).
      More adverse events were recorded in PACU after introduction of the PACT (8.3% vs
      16.7%, P<0.001). The rate of adverse events after discharge from PACU remained
      constant (16.5%), but the rate of cardiac events (5.1% vs 2.6%, P=0.021) and
      clinical deterioration (8.7% vs 4.3%, P=0.001) following PACU discharge
      significantly decreased, using the PACT. Despite the increased number of patients
      with adverse events in phase 2, healthcare costs did not increase significantly.
      Length of stay in PACU and length of hospital admission for those patients who
      had an adverse event in PACU were significantly reduced after implementation of
      the PACT. CONCLUSION: This study found that using a structured discharge criteria
      tool, the PACT, enhanced nurses' recognition and response to patients who
      experienced clinical deterioration, reduced length of stay for patients who
      experienced an adverse event in PACU and was cost-effective.

PMID- 29203502
TI  - Characteristics of NPS use in patients admitted to acute psychiatric services in
      Southeast Scotland: a retrospective cross-sectional analysis following public
      health interventions.
AB  - OBJECTIVES: Assess the impact of selective prohibition and seizure of novel
      psychoactive substances (NPS) supply on NPS use prevalence within psychiatric
      admissions and evaluate demographic characteristics of current NPS users. DESIGN:
      A 6-month retrospective cross-sectional analysis of discharge letters between 1
      October 2015 and 31 March 2016. SETTING: General psychiatry inpatients and
      intensive home treatment team (IHTT) community patients at a psychiatric hospital
      in a Scottish city. PARTICIPANTS: All participants were between the ages of 18
      and 65 years. After application of exclusion criteria, 473 discharge letters of
      general psychiatry patients were deemed suitable for analysis and 264 IHTT
      patient discharge letters were analysed. INTERVENTIONS: A nationwide temporary
      class drug order (TCDO) was placed on 10 April 2015 reclassifying methylphenidate
      related compounds as class B substances. On 15 October 2015, local forfeiture
      orders were granted to trading standards permitting the seizure of NPS supplies.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was to
      determine the prevalence of NPS use in two cohorts. Second, demographic features
      of patients and details regarding their psychiatric presentation were analysed.
      RESULTS: The prevalence of NPS use in general psychiatry and IHTT patients was
      6.6% and 3.4%, respectively. Inpatients using NPS compared with non-users were
      more likely to be men (OR 2.92, 95% CI 1.28 to 6.66, P=0.009), have a forensic
      history (OR 5.03, CI 2.39 to 10.59, P<0.001) and be detained under an Emergency
      Detention Certificate (OR 3.50, CI 1.56 to 7.82, P=0.004). NPS users were also
      more likely to be diagnosed under International Statistical Classification of
      Diseases and Related Health Problems, Version 10, F10-19 (OR 9.97, CI 4.62 to
      21.49, P<0.001). CONCLUSIONS: Compared with previous work, psychiatric inpatient
      NPS use has fallen. NPS continue to be used by a demographic previously described
      resulting in presentations consistent with a drug-induced psychosis and at times
      requiring detention under the Mental Health Act. Further research is required to
      evaluate the effectiveness of the recent prohibition of all NPS.

PMID- 29203503
TI  - Multicentre prospective randomised single-blind controlled study protocol of the
      effect of an additional parent-administered sensorimotor stimulation on
      neurological development of preterm infants: Primebrain.
AB  - INTRODUCTION: Preterm and very low birthweight infants are at increased risk for
      neurodevelopmental disorders, including cerebral palsy, sensory impairment and
      intellectual disability. Several early intervention approaches have been designed
      in the hope of optimising neurological development in this context. It seems
      important that the intervention takes into account parental mental health,
      focuses on parent-child interactions and lasts sufficiently long. This study aims
      to evaluate the effects of a stimulation programme administered by parents until
      6 months post-term on motor and neurophysiological development of infants born
      preterm. METHODS AND ANALYSIS: Participants will be infants born <32 weeks'
      gestation and/or with a birth weight <1500 g recruited prospectively from two
      tertiary neonatal intensive care units. They will be randomly assigned to receive
      nationally recommended follow-up only (control group) or also a stimulation
      programme between 37 weeks' gestation and 6 months' corrected age. Perinatal,
      clinical neurodevelopmental, socio-demographic and neuroimaging (ultrasonography
      or MRI) data will be collected. Bayley Scales of Infant Development will be used
      up to 24 months' corrected age and Parental Stress Index at 6, 12, 18 and 24
      months' corrected age. High-density (64 or 128 electrodes) EEG, visual,
      somatosensory and long latency auditory evoked potentials will be recorded at
      term age, 3, 6, 12, 18 and 24 months' corrected age. They will be analysed for
      spatiotemporal frequency bands contents and source localisation. ETHICS AND
      DISSEMINATION: The study was approved by the Ethics Committees of the Hopital
      Universitaire des Enfants Reine Fabiola and CHU Saint-Pierre. Results
      dissemination will be made for stakeholders and families, reports will be written
      for parents, healthcare providers and policymakers, and scientific papers will be
      published. TRIAL REGISTRATION NUMBER: NCT02159534; Pre-results.

PMID- 29203504
TI  - Frequencies and ethnic distribution of ABO and RhD blood groups in China: a
      population-based cross-sectional study.
AB  - OBJECTIVES: ABO and RhD blood groups are key factors affecting blood transfusion
      safety. The distribution of ABO and RhD blood groups varies globally, but limited
      data exist for ethnic distributions of these blood groups in Asian populations.
      We aimed to evaluate the distribution of ABO and RhD blood groups among Chinese
      ethnic groups. DESIGN: A population-based cross-sectional study. SETTING: Data on
      ABO groups and ethnicities were obtained from the National Free Preconception
      Health Examination Project (NFPHEP) with participants from 220 counties of 31
      provinces in China PARTICIPANTS: There were 3 832 034 participants aged 21-49
      years who took part in the NFPHEP from January 2010 to December 2012 and were
      included in this study. OUTCOME MEASURES: The proportion of ABO and RhD blood
      groups among different ethnic groups was calculated. RESULTS: ABO and RhD blood
      distribution was significantly different among nine ethnic groups (P<0.001).
      Compared with other ethnic groups, the Yi group had more A phenotypes (34.0%),
      and the Manchu (33.7%) and Mongolian (33.3%) ethnic groups had more B phenotypes.
      The Zhuang group had the greatest proportion of O phenotypes (41.8%), followed by
      the Miao group (37.7%). AB phenotypes were more frequent in the Uygur ethnic
      group (10.6%) but lower in the Zhuang group (5.5%). Meanwhile, RhD negativity
      (RhD-) was greater in the Uygur group (3.3%) than in the Mongolian (0.3%) and
      Manchu ethnic groups (0.4%). O RhD- blood groups were more frequent in the Uygur
      group (0.8%) than in the other ethnic groups (0.1%-0.4%, P<0.001). CONCLUSION:
      ABO and RhD blood phenotypes vary across different ethnic groups in China. The
      diversity in the distribution of the ABO and RhD blood groups in different ethnic
      groups should be considered when developing rational and evidence-based
      strategies for blood collection and management.

PMID- 29203505
TI  - Obesity prevalence among healthcare professionals in England: a cross-sectional
      study using the Health Survey for England.
AB  - OBJECTIVE: To estimate obesity prevalence among healthcare professionals in
      England and compare prevalence with those working outside of the health services.
      DESIGN: Cross-sectional study based on data from 5 years (2008-2012) of the
      nationally representative Health Survey for England. SETTING: England.
      PARTICIPANTS: 20 103 adults aged 17-65 years indicating they were economically
      active at the time of survey classified into four occupational groups: nurses
      (n=422), other healthcare professionals (n=412), unregistered care workers
      (n=736) and individuals employed in non-health-related occupations (n=18 533).
      OUTCOME MEASURE: Prevalence of obesity defined as body mass index >=30.0 with 95%
      CIs and weighted to reflect the population. RESULTS: Obesity prevalence was high
      across all occupational groups including: among nurses (25.1%, 95% CI 20.9% to
      29.4%); other healthcare professionals (14.4%, 95% CI 11.0% to 17.8%); non-health
      related occupations (23.5%, 95% CI 22.9% to 24.1%); and unregistered care workers
      who had the highest prevalence of obesity (31.9%, 95% CI 28.4% to 35.3%). A
      logistic regression model adjusted for sociodemographic composition and survey
      year indicated that, compared with nurses, the odds of being obese were
      significantly lower for other healthcare professionals (adjusted OR (aOR) 0.52,
      95% CI 0.37 to 0.75) and higher for unregistered care workers (aOR 1.46, 95% CI
      1.11 to 1.93). There was no significant difference in obesity prevalence between
      nurses and people working in non-health-related occupations (aOR 0.94, 95% CI
      0.74 to 1.18). CONCLUSIONS: High obesity prevalence among nurses and unregistered
      care workers is concerning as it increases the risks of musculoskeletal
      conditions and mental health conditions that are the main causes of sickness
      absence in health services. Further research is required to better understand the
      reasons for high obesity prevalence among healthcare professionals in England to
      inform interventions to support individuals to achieve and maintain a healthy
      weight.

PMID- 29203506
TI  - Effectiveness of preoperative medical consultations by internal medicine
      physicians: a systematic review.
AB  - OBJECTIVE: Clinics have been established to provide preoperative medical
      consultations, and enable the anaesthetist and surgeon to deliver the best
      surgical outcome for patients. However, there is uncertainty regarding the effect
      of such clinics on surgical, in-hospital and long-term outcomes. A systematic
      review of the literature was conducted to determine the effectiveness of
      preoperative medical consultations by internal medicine physicians for patients
      listed for elective surgery. DESIGN: Systematic searches of MEDLINE, EMBASE,
      CINAHL, PubMed, Current Contents and the NHS Centre for Reviews and Dissemination
      were conducted up to 30 April 2017. SETTING: Elective surgery. STUDY SELECTION:
      Randomised controlled trials and non-randomised comparative studies conducted in
      adults. OUTCOME MEASURES: Length of hospital stay, perioperative morbidity and
      mortality, costs and quality of life. RESULTS: The one randomised trial reported
      that preadmission preoperative assessment was more effective than the option of
      an inpatient medical assessment in reducing the frequency of unnecessary
      admissions with significantly fewer surgical cancellations following admission
      for surgery. A small reduction in length of stay in patients was also observed.
      The three non-randomised studies reported increased lengths of stay, costs and
      postoperative complications in patients who received preoperative assessment. The
      timing and delivery of the preoperative medical consultation in the intervention
      group differed across the included studies. CONCLUSION: Further research is
      required to inform the design and implementation of coordinated involvement of
      physicians and surgeons in the provision of care for high-risk surgical patients.
      A standardised approach to perioperative decision-making processes should be
      developed with a clear protocol or guideline for the assessment and management of
      surgical patients.

PMID- 29203507
TI  - The short-term health and economic burden of gestational diabetes mellitus in
      China: a modelling study.
AB  - OBJECTIVES: Gestational diabetes mellitus (GDM) is associated with a higher risk
      for adverse health outcomes during pregnancy and delivery for both mothers and
      babies. This study aims to assess the short-term health and economic burden of
      GDM in China in 2015. DESIGN: Using TreeAge Pro, an analytical decision model was
      built to estimate the incremental costs and quality-of-life loss due to GDM, in
      comparison with pregnancy without GDM from the 28th gestational week until and
      including childbirth. The model was populated with probabilities and costs based
      on current literature, clinical guidelines, price lists and expert interviews.
      Deterministic and probabilistic sensitivity analyses were performed to test the
      robustness of the results. PARTICIPANTS: Chinese population who gave birth in
      2015. RESULTS: On average, the cost of a pregnancy with GDM was Y6677.37 (in 2015
      international $1929.87) more (+95%) than a pregnancy without GDM, due to
      additional expenses during both the pregnancy and delivery: Y4421.49 for GDM
      diagnosis and treatment, Y1340.94 (+26%) for the mother's complications and
      Y914.94 (+52%) for neonatal complications. In China, 16.5 million babies were
      born in 2015. Given a GDM prevalence of 17.5%, the number of pregnancies affected
      by GDM was estimated at 2.90 million in 2015. Therefore, the annual societal
      economic burden of GDM was estimated to be Y19.36 billion (international $5.59
      billion). Sensitivity analyses were used to confirm the robustness of the
      results. Incremental health losses were estimated to be approximately 260 000
      quality-adjusted life years. CONCLUSION: In China, the GDM economic burden is
      significant, even in the short-term perspective and deserves more attention and
      awareness. Our findings indicate a clear need to implement GDM prevention and
      treatment strategies at a national level in order to reduce the economic and
      health burden at both the population and individual levels.

PMID- 29203508
TI  - Early warning scores for detecting deterioration in adult hospital patients: a
      systematic review protocol.
AB  - INTRODUCTION: Early warning scores (EWSs) are used extensively to identify
      patients at risk of deterioration in hospital. Previous systematic reviews
      suggest that studies which develop EWSs suffer methodological shortcomings and
      consequently may fail to perform well. The reviews have also identified that few
      validation studies exist to test whether the scores work in other settings. We
      will aim to systematically review papers describing the development or validation
      of EWSs, focusing on methodology, generalisability and reporting. METHODS: We
      will identify studies that describe the development or validation of EWSs for
      adult hospital inpatients. Each study will be assessed for risk of bias using the
      Prediction model Risk of Bias ASsessment Tool (PROBAST). Two reviewers will
      independently extract information. A narrative synthesis and descriptive
      statistics will be used to answer the main aims of the study which are to assess
      and critically appraise the methodological quality of the EWS, to describe the
      predictors included in the EWSs and to describe the reported performance of EWSs
      in external validation. ETHICS AND DISSEMINATION: This systematic review will
      only investigate published studies and therefore will not directly involve
      patient data. The review will help to establish whether EWSs are fit for purpose
      and make recommendations to improve the quality of future research in this area.
      PROSPERO REGISTRATION NUMBER: CRD42017053324.

PMID- 29203509
TI  - Protocol for a feasibility study and randomised pilot trial of a low-intensity
      psychological intervention for depression in adults with autism: the Autism
      Depression Trial (ADEPT).
AB  - INTRODUCTION: High rates of co-occurring depression are reported in autism
      spectrum disorder (ASD), a neurodevelopmental condition characterised by social
      communication impairments and repetitive behaviours. Cognitive-behavioural
      interventions adapted for ASD have been effective for anxiety problems. There
      have been evaluation studies of group cognitive-behavioural therapy for co
      occurring depression, but no randomised trials investigating low-intensity
      psychological interventions as recommended in clinical guidelines for mild
      moderate depression. METHODS AND ANALYSIS: A feasibility study comprising a
      randomised controlled trial (RCT) and nested qualitative evaluation is under way
      as preparation for a definitive RCT. Participants (n=70) will be randomised to
      Guided Self-Help: a low-intensity psychological intervention based on behavioural
      activation adapted for ASD or treatment as usual. Outcomes including depression
      symptoms, anxiety, social function and service use will be measured at 10, 16 and
      24 weeks postrandomisation and will be blind to group allocation for measures
      that are not self-administered. The analysis will aim to establish the rates of
      recruitment and retention for a larger-scale RCT as well as the most appropriate
      measure of depression to serve as primary outcome. The qualitative study will
      purposively sample up to 24 participants from each treatment group to consider
      the acceptability and feasibility of the intervention and the trial design.
      ETHICS AND DISSEMINATION: Ethical approval has been received from WALES REC 3
      (IRAS project ID: 191558) and the Health Research Authority with R&D approval
      from Avon and Wiltshire Mental Health Partnership and Northumberland, Tyne and
      Wear Foundation NHS Trusts. To our knowledge, this is the first study of a low
      intensity intervention for depression in adults with autism. The results will
      inform the design of a definitive RCT. Dissemination will include peer-reviewed
      journal publications reporting the quantitative and qualitative research findings
      of the study and presentations at national and international conferences. TRIAL
      REGISTRATION NUMBER: ISRCTN54650760; Pre-results.

PMID- 29203510
TI  - Mechanisms to Elevate Endogenous GLP-1 Beyond Injectable GLP-1 Analogs and
      Metabolic Surgery.
AB  - Therapeutic engineering of glucagon-like peptide 1 (GLP-1) has enabled
      development of new medicines to treat type 2 diabetes. These injectable analogs
      achieve robust glycemic control by increasing concentrations of "GLP-1
      equivalents" (~50 pmol/L). Similar levels of endogenous GLP-1 occur after gastric
      bypass surgery, and mechanistic studies indicate glucose lowering by these
      procedures is driven by GLP-1. Therefore, because of the remarkable signaling and
      secretory capacity of the GLP-1 system, we sought to discover mechanisms that
      increase GLP-1 pharmacologically. To study active GLP-1, glucose-dependent
      insulinotropic polypeptide receptor (Gipr)-deficient mice receiving background
      dipeptidyl peptidase 4 (DPP4) inhibitor treatment were characterized as a model
      for evaluating oral agents that increase circulating GLP-1. A somatostatin
      receptor 5 antagonist, which blunts inhibition of GLP-1 release, and agonists for
      TGR5 and GPR40, which stimulate GLP-1 secretion, were investigated alone and in
      combination with the DPP4 inhibitor sitagliptin; these only modestly increased
      GLP-1 (~5-30 pmol/L). However, combining molecules to simultaneously intervene at
      multiple regulatory nodes synergistically elevated active GLP-1 to unprecedented
      concentrations (~300-400 pmol/L), drastically reducing glucose in Gipr null and
      Leprdb/db mice in a GLP-1 receptor-dependent manner. Our studies demonstrate that
      complementary pathways can be engaged to robustly increase GLP-1 without invasive
      surgical or injection regimens.

PMID- 29203511
TI  - Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body
      Composition, Liver Lipid Content, and Hepatic Insulin Signaling.
AB  - Disruption of hepatocyte growth hormone (GH) signaling through disruption of Jak2
      (JAK2L) leads to fatty liver. Previously, we demonstrated that development of
      fatty liver depends on adipocyte GH signaling. We sought to determine the
      individual roles of hepatocyte and adipocyte Jak2 on whole-body and tissue
      insulin sensitivity and liver metabolism. On chow, JAK2L mice had hepatic
      steatosis and severe whole-body and hepatic insulin resistance. However,
      concomitant deletion of Jak2 in hepatocytes and adipocytes (JAK2LA) completely
      normalized insulin sensitivity while reducing liver lipid content. On high-fat
      diet, JAK2L mice had hepatic steatosis and insulin resistance despite protection
      from diet-induced obesity. JAK2LA mice had higher liver lipid content and no
      protection from obesity but retained exquisite hepatic insulin sensitivity. AKT
      activity was selectively attenuated in JAK2L adipose tissue, whereas hepatic
      insulin signaling remained intact despite profound hepatic insulin resistance.
      Therefore, JAK2 in adipose tissue is epistatic to liver with regard to insulin
      sensitivity and responsiveness, despite fatty liver and obesity. However,
      hepatocyte autonomous JAK2 signaling regulates liver lipid deposition under
      conditions of excess dietary fat. This work demonstrates how various tissues
      integrate JAK2 signals to regulate insulin/glucose and lipid metabolism.

PMID- 29203513
TI  - IL-3 Differentially Regulates Membrane and Soluble RANKL in Osteoblasts through
      Metalloproteases and the JAK2/STAT5 Pathway and Improves the RANKL/OPG Ratio in
      Adult Mice.
AB  - Bone remodeling comprises balanced activities between osteoclasts and
      osteoblasts, which is regulated by various factors, including hormones and
      cytokines. We previously reported that IL-3 inhibits osteoclast differentiation
      and pathological bone loss. IL-3 also enhances osteoblast differentiation and
      bone formation from mesenchymal stem cells. However, the role of IL-3 in
      regulation of osteoblast-osteoclast interactions and underlying mechanisms is not
      yet delineated. In this study, we investigated the role of IL-3 on the regulation
      of osteoblast-specific molecules, receptor activator of NF-kappaB ligand (RANKL),
      and osteoprotegerin (OPG) that modulate bone homeostasis. We found that IL-3
      increases RANKL expression at both the transcriptional and translational levels,
      and it showed no effect on OPG expression in calvarial osteoblasts. The increased
      RANKL expression by IL-3 induces mononuclear osteoclasts; however, it does not
      induce multinuclear osteoclasts. Interestingly, IL-3 decreases soluble RANKL by
      reducing ectodomain shedding of membrane RANKL through downregulation of
      metalloproteases mainly a disintegrin and metalloproteinase (ADAM)10, ADAM17,
      ADAM19, and MMP3. Moreover, IL-3 increases membrane RANKL by activating the
      JAK2/STAT5 pathway. Furthermore, IL-3 enhances RANKL expression in mesenchymal
      stem cells of wild-type mice but not in STAT5a knockout mice. Interestingly, IL-3
      restores RANKL expression in adult mice by enhancing bone-specific RANKL and
      decreasing serum RANKL. Furthermore, IL-3 increases the serum OPG level in adult
      mice. Thus, our results reveal, to our knowledge for the first time, that IL-3
      differentially regulates two functional forms of RANKL through metalloproteases
      and the JAK2/STAT5 pathway, and it helps in restoring the decreased RANKL/OPG
      ratio in adult mice. Notably, our studies indicate the novel role of IL-3 in
      regulating bone homeostasis in important skeletal disorders.

PMID- 29203512
TI  - Glucocorticoids Reprogram beta-Cell Signaling to Preserve Insulin Secretion.
AB  - Excessive glucocorticoid exposure has been shown to be deleterious for pancreatic
      beta-cell function and insulin release. However, glucocorticoids at physiological
      levels are essential for many homeostatic processes, including glycemic control.
      We show that corticosterone and cortisol and their less active precursors 11
      dehydrocorticosterone (11-DHC) and cortisone suppress voltage-dependent Ca2+
      channel function and Ca2+ fluxes in rodent as well as in human beta-cells.
      However, insulin secretion, maximal ATP/ADP responses to glucose, and beta-cell
      identity were all unaffected. Further examination revealed the upregulation of
      parallel amplifying cAMP signals and an increase in the number of membrane-docked
      insulin secretory granules. Effects of 11-DHC could be prevented by lipotoxicity
      and were associated with paracrine regulation of glucocorticoid activity because
      global deletion of 11beta-hydroxysteroid dehydrogenase type 1 normalized Ca2+ and
      cAMP responses. Thus, we have identified an enzymatically amplified feedback loop
      whereby glucocorticoids boost cAMP to maintain insulin secretion in the face of
      perturbed ionic signals. Failure of this protective mechanism may contribute to
      diabetes in states of glucocorticoid excess, such as Cushing syndrome, which are
      associated with frank dyslipidemia.

PMID- 29203514
TI  - Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin.
AB  - An important entraining signal for the endogenous circadian clock, independent of
      light, is food intake. The circadian and immune systems are linked; forced
      desynchrony of the circadian clock via nighttime light exposure or genetic
      ablation of core clock components impairs immune function. The timing of food
      intake affects various aspects of the circadian clock, but its effects on immune
      function are unknown. We tested the hypothesis that temporal desynchrony of food
      intake alters innate immune responses. Adult male Swiss Webster mice were
      provided with food during the night, the day, or ad libitum for 4 wk, followed by
      administration of LPS prior to the onset of either the active phase (zeitgeber
      time [ZT]12: Experiment 1) or the inactive phase (ZT0: Experiment 2). Three hours
      after LPS administration, blood was collected, and serum was tested for bacteria
      killing capacity against Escherichia coli, as a functional assay of immune
      function. Additionally, cytokine expression was examined in the serum (protein),
      spleen, and hypothalamus (mRNA). Day-fed mice suppressed bacteria-killing
      capacity and serum cytokine responses to LPS during the active phase (ZT12).
      Night-fed mice increased bactericidal capacity, as well as serum and hypothalamic
      mRNA responses of certain proinflammatory cytokines during the active phase. Only
      day-fed mice enhanced serum cytokine responses when LPS challenge occurred during
      the inactive phase (ZT0); this did not result in enhanced bactericidal capacity.
      These data suggest that mistimed feeding has functional relevance for immune
      function and provide further evidence for the integration of the circadian,
      metabolic, and immune systems.

PMID- 29203518
TI  - DNA methylation in epigenetic inheritance of metabolic diseases through the male
      germ line.
AB  - The global rise in metabolic diseases can be attributed to a complex interplay
      between biology, behavior and environmental factors. This article reviews the
      current literature concerning DNA methylation-based epigenetic inheritance
      (intergenerational and transgenerational) of metabolic diseases through the male
      germ line. Included are a presentation of the basic principles for DNA
      methylation in developmental programming, and a description of windows of
      susceptibility for the inheritance of environmentally induced aberrations in DNA
      methylation and their associated metabolic disease phenotypes. To this end,
      escapees, genomic regions with the intrinsic potential to transmit acquired
      paternal epigenetic information across generations by escaping the extensive
      programmed DNA demethylation that occurs during gametogenesis and in the zygote,
      are described. The ongoing descriptive and functional examinations of DNA
      methylation in the relevant biological samples, in conjugation with analyses of
      non-coding RNA and histone modifications, hold promise for improved delineation
      of the effect size and mechanistic background for epigenetic inheritance of
      metabolic diseases.

PMID- 29203515
TI  - Brucella abortus Triggers a cGAS-Independent STING Pathway To Induce Host
      Protection That Involves Guanylate-Binding Proteins and Inflammasome Activation.
AB  - Immunity against microbes depends on recognition of pathogen-associated molecular
      patterns by innate receptors. Signaling pathways triggered by Brucella abortus
      DNA involves TLR9, AIM2, and stimulator of IFN genes (STING). In this study, we
      observed by microarray analysis that several type I IFN-associated genes, such as
      IFN-beta and guanylate-binding proteins (GBPs), are downregulated in STING
      knockout (KO) macrophages infected with Brucella or transfected with DNA.
      Additionally, we determined that STING and cyclic GMP-AMP synthase (cGAS) are
      important to engage the type I IFN pathway, but only STING is required to induce
      IL-1beta secretion, caspase-1 activation, and GBP2 and GBP3 expression.
      Furthermore, we determined that STING but not cGAS is critical for host
      protection against Brucella infection in macrophages and in vivo. This study
      provides evidence of a cGAS-independent mechanism of STING-mediated protection
      against an intracellular bacterial infection. Additionally, infected IFN
      regulatory factor-1 and IFNAR KO macrophages had reduced GBP2 and GBP3 expression
      and these cells were more permissive to Brucella replication compared with wild
      type control macrophages. Because GBPs are critical to target vacuolar bacteria,
      we determined whether GBP2 and GBPchr3 affect Brucella control in vivo. GBPchr3
      but not GBP2 KO mice were more susceptible to bacterial infection, and small
      interfering RNA treated-macrophages showed reduction in IL-1beta secretion and
      caspase-1 activation. Finally, we also demonstrated that Brucella DNA colocalizes
      with AIM2, and AIM2 KO mice are less resistant to B. abortus infection. In
      conclusion, these findings suggest that the STING-dependent type I IFN pathway is
      critical for the GBP-mediated release of Brucella DNA into the cytosol and
      subsequent activation of AIM2.

PMID- 29203517
TI  - Uroguanylin: a new actor in the energy balance movie.
AB  - Uroguanylin (UGN) is a potential target in the fight against obesity. The mature
      protein is released after enzymatic cleavage from its natural precursor, proUGN.
      UGN is mostly produced in the gut, and its production is regulated by nutritional
      status. However, UGN is also produced in other tissues such as the kidneys. In
      the past, UGN has been widely studied as a natriuretic peptide owing to its
      involvement in several different pathologies such as heart failure, cancer and
      gastrointestinal diseases. However, recent studies have suggested that UGN also
      acts as a regulator of body weight homeostasis because it modulates both food
      intake and energy expenditure. This ultimately results in a decrease in body
      weight. This action is mediated by the sympathetic nervous system. Future studies
      should be directed at the potential effects of UGN agonists in regulating body
      weight in human obesity.

PMID- 29203516
TI  - Alternative Splicing Transcripts of Zebrafish LGP2 Gene Differentially Contribute
      to IFN Antiviral Response.
AB  - In mammals, RIG-I like receptors (RLRs) RIG-I and melanoma differentiation
      associated gene 5 (MDA5) sense cytosolic viral RNA, leading to IFN antiviral
      response; however, LGP2 exhibits controversial functions. The same happens to
      fish LGP2. In this study we report that three zebrafish LGP2 splicing
      transcripts, a full-length LGP2, and two truncating variants, LGP2v1 and LGP2v2,
      play distinct roles during IFN antiviral response. Overexpression of the full
      length LGP2 not only potentiates IFN response through the RLR pathway, in the
      absence or presence of poly(I:C) at limited concentrations, but also inhibits IFN
      response by relative high concentrations of poly(I:C) through functional
      attenuation of signaling factors involved in the RLR pathway; however, LGP2v1 and
      LGP2v2 only retain the inhibitory role. Consistently, LGP2 but not LGP2v1 and
      LGP2v2 confers protection on fish cells against spring viremia of carp virus
      (SVCV) infection and at limited expression levels, LGP2 exerts more significant
      protection than either RIG-I or MDA5. Further data suggest that in the early
      phase of SVCV infection, LGP2 functions as a positive regulator but along with
      SVCV replicating in cells up to a certain titer, which leads to a far more robust
      expression of IFN, LGP2 switches to a negative role. These in vitro results
      suggest an ingenious mechanism where the three zebrafish LGP2 splicing
      transcripts work cooperatively to shape IFN antiviral responses.

PMID- 29203519
TI  - S1P1 Modulator-Induced G alphai Signaling and beta-Arrestin Recruitment Are Both
      Necessary to Induce Rapid and Efficient Reduction of Blood Lymphocyte Count In
      Vivo.
AB  - S1P1 (sphingosine-1-phosphate receptor 1) agonists prevent lymphocyte egress from
      secondary lymphoid organs and cause a reduction in the number of circulating
      blood lymphocytes. We hypothesized that S1P1 receptor modulators with pathway
      selective signaling properties could help to further elucidate the molecular
      mechanisms involved in lymphocyte trapping. A proprietary S1P1 receptor modulator
      library was screened for compounds with clear potency differences in beta
      arrestin recruitment and G protein alpha i subunit (G alphai) protein-mediated
      signaling. We describe here the structure-activity relationships of highly potent
      S1P1 modulators with apparent pathway selectivity for beta-arrestin recruitment.
      The most differentiated compound, D3-2, displayed a 180-fold higher potency in
      the beta-arrestin recruitment assay (EC50 0.9 nM) compared with the G alphai
      activation assay (167 nM), whereas ponesimod, a S1P1 modulator that is currently
      in advanced clinical development in multiple sclerosis, was equipotent in both
      assays (EC50 1.5 and 1.1 nM, respectively). Using these novel compounds as
      pharmacological tools, we showed that although a high potency in beta-arrestin
      recruitment is required to fully internalize S1P1 receptors, the potency in
      inducing G alphai signaling determines the rate of receptor internalization in
      vitro. In contrast to ponesimod, the compound D3-2 did not reduce the number or
      circulating lymphocytes in rats despite high plasma exposures. Thus, for rapid
      and maximal S1P1 receptor internalization a high potency in both G alphai
      signaling and beta-arrestin recruitment is mandatory and this translates into
      efficient reduction of the number of circulating lymphocytes in vivo.

PMID- 29203520
TI  - Opioids and Operations.

PMID- 29203521
TI  - Persistent Opioid Use Among Pediatric Patients After Surgery.
AB  - BACKGROUND: Despite efforts to reduce nonmedical opioid misuse, little is known
      about the development of persistent opioid use after surgery among adolescents
      and young adults. We hypothesized that there is an increased incidence of
      prolonged opioid refills among adolescents and young adults who received
      prescription opioids after surgery compared with nonsurgical patients. METHODS:
      We performed a retrospective cohort study by using commercial claims from the
      Truven Health Marketscan research databases from January 1, 2010, to December 31,
      2014. We included opioid-naive patients ages 13 to 21 years who underwent 1 of 13
      operations. A random sample of 3% of nonsurgical patients who matched eligibility
      criteria was included as a comparison. Our primary outcome was persistent opioid
      use, which was defined as >=1 opioid prescription refill between 90 and 180 days
      after the surgical procedure. RESULTS: Among eligible patients, 60.5% filled a
      postoperative opioid prescription (88 637 patients). Persistent opioid use was
      found in 4.8% of patients (2.7%-15.2% across procedures) compared with 0.1% of
      those in the nonsurgical group. Cholecystectomy (adjusted odds ratio 1.13; 95%
      confidence interval, 1.00-1.26) and colectomy (adjusted odds ratio 2.33; 95%
      confidence interval, 1.01-5.34) were associated with the highest risk of
      persistent opioid use. Independent risk factors included older age, female sex,
      previous substance use disorder, chronic pain, and preoperative opioid fill.
      CONCLUSIONS: Persistent opioid use after surgery is a concern among adolescents
      and young adults and may represent an important pathway to prescription opioid
      misuse. Identifying safe, evidence-based practices for pain management is a top
      priority, particularly among at-risk patients.

PMID- 29203522
TI  - E-Cigarettes: A 1-Way Street to Traditional Smoking and Nicotine Addiction for
      Youth.

PMID- 29203523
TI  - Trajectories of E-Cigarette and Conventional Cigarette Use Among Youth.
AB  - BACKGROUND: Electronic cigarette (e-cigarette) use is common among youth, and
      there are concerns that e-cigarette use leads to future conventional cigarette
      use. We examined longitudinal associations between past-month cigarette and e
      cigarette use to characterize the stability and directionality of these tobacco
      use trajectories over time. METHODS: High school students (N = 808, 53% female)
      completed surveys across 3 waves (2013, 2014, and 2015) in 3 public schools in
      Connecticut. Using autoregressive cross-lagged models, we examined bidirectional
      relationships between past-month cigarette and e-cigarette use over time. Models
      were adjusted for covariates related to tobacco use (ie, sex, race/ethnicity,
      socioeconomic status, and use of other tobacco products). RESULTS: Past-month e
      cigarette use predicted future cigarette use (wave 1-2: odds ratio [OR] = 7.08,
      95% confidence interval [CI] = 2.34-21.42; wave 2-3: OR = 3.87, 95% CI = 1.86
      8.06). However, past-month cigarette use did not predict future e-cigarette use
      (wave 1-2: OR = 2.02, 95% CI = 0.67-6.08; wave 2-3: OR = 1.90, 95% CI = 0.77
      4.71). Additionally, frequency of cigarette and e-cigarette use increased over
      time. By wave 3, 26% of cigarette users and 20.5% of e-cigarette users reported
      using 21-30 days out of the past month. CONCLUSIONS: E-cigarette use was
      associated with future cigarette use across 3 longitudinal waves, yet cigarette
      use was not associated with future e-cigarette use. Future research needs to
      examine mechanisms through which e-cigarette use leads to cigarette use. E
      cigarette regulation and prevention programs may help prevent future use of
      cigarettes among youth.

PMID- 29203524
TI  - Trends in adolescent mental health during economic upturns and downturns: a
      multilevel analysis of Swedish data 1988-2008.
AB  - BACKGROUND: A long-term trend of increasing mental health problems among
      adolescents in many Western countries indicates a great need to investigate if
      and how societal changes have contributed to the reported increase. Using seven
      waves of repeated cross-sectional data collected between 1988 and 2008 in Sweden,
      the current study examined if economic factors at the societal level
      (municipality unemployment rate) and at the individual level (worry about family
      finances), and their interaction could explain a secular trend in mental health
      problems. METHODS: Participants were 17 533 students of age 15-16 years (49.3%
      girls), from 14 municipalities in a county of Sweden. Data on adolescents' mental
      health (psychosomatic problems) and worry about family finances were obtained
      using a self-report questionnaire. A series of multilevel regression analyses
      were conducted in order to explain the trends in adolescents' mental health.
      RESULTS: The results indicated that the individual-level predictor (worry about
      family finances) significantly explained the increasing rates of adolescents'
      psychosomatic problems. This was particularly the case during the mid-1990s,
      which was characterised by a severe recession in Sweden with high unemployment
      rates. For example, after accounting for adolescents' worry, a significant
      increase in psychosomatic symptoms between 1988 and 1998 among girls (b=0.112,
      P<0.05) disappeared (b=0.018, P>0.05) and a non-significant decrease between 1988
      and 1995 among boys (b=-0.017, P>0.05) became significant (b=-0.142, P<0.05).
      Neither municipality unemployment rate nor its interaction with adolescents'
      worry explained psychosomatic problems. CONCLUSIONS: The findings demonstrate the
      effects of adolescents' worry about family finances on a secular trend in mental
      health problems during an economically bleak period of time. The study highlights
      the need for repeated measurements including a large number of time points over a
      long time period in order to analyse time-specific putative explanatory factors
      for trends in adolescent mental health problems.

PMID- 29203525
TI  - Methodological, political and legal issues in the assessment of the effects of
      nanotechnology on human health.
AB  - Engineered nanomaterials (ENMs) raise questions among the scientific community
      and public health authorities about their potential risks to human health.
      Studying a prospective cohort of workers exposed to ENMs would be considered the
      gold standard for identifying potential health effects of nanotechnology and
      confirming the 'no effect' levels derived from cellular and animal models.
      However, because only small, cross-sectional studies have been conducted in the
      past 5 years, questions remain about the health risks of ENMs. This essay
      addresses the scientific, methodological, political and regulatory issues that
      make epidemiological research in nanotechnology-exposed communities particularly
      complex. Scientific challenges include the array of physicochemical parameters
      and ENM production conditions, the lack of universally accepted definitions of
      ENMs and nanotechnology workers, and the lack of information about modes of
      action, target organs and likely dose-response functions of ENMs. Standardisation
      of data collection and harmonisation of research protocols are needed to
      eliminate misclassification of exposures and health effects. Forming ENM worker
      cohorts from a combination of smaller cohorts and overcoming selection bias are
      also challenges. National or international registries for monitoring the
      exposures and health of ENM workers would be helpful for epidemiological studies,
      but the creation of such a registry and ENM worker cohorts will require political
      support and dedicated funding at the national and international levels. Public
      authorities and health agencies should consider carrying out an ENM awareness
      campaign to educate and engage all stakeholders and concerned communities in
      discussion of such a project.

PMID- 29203526
TI  - Caveolin-1 regulates lipid droplet metabolism in endothelial cells via autocrine
      prostacyclin-stimulated, cAMP-mediated lipolysis.
AB  - Lipid droplets (LD) are dynamic organelles involved in intracellular lipid
      metabolism in almost all eukaryotic cells, and LD-associated proteins tightly
      regulate their dynamics. One LD coat protein is caveolin-1 (Cav-1), an essential
      component for caveola assembly in highly differentiated cells, including
      adipocytes, smooth muscle cells, and endothelial cells (EC). However, the role of
      Cav-1 in LD dynamics is unclear. Here we report that EC lacking Cav-1 exhibit
      impaired LD formation. The decreased LD formation is due to enhanced lipolysis
      and not caused by reduced triglyceride synthesis or fatty acid uptake.
      Mechanistically, the absence of Cav-1 increased cAMP/PKA signaling in EC, as
      indicated by elevated phosphorylation of hormone-sensitive lipase and increased
      lipolysis. Unexpectedly, we also observed enhanced autocrine production of
      prostaglandin I2 (PGI2, also called prostacyclin) in Cav-1 KO EC, and this PGI2
      increase appeared to stimulate cAMP/PKA pathways, contributing to the enhanced
      lipolysis in Cav-1 KO cells. Our results reveal an unanticipated role of Cav-1 in
      regulating lipolysis in non-adipose tissue, indicating that Cav-1 is required for
      LD metabolism in EC and that it regulates cAMP-dependent lipolysis in part via
      the autocrine production of PGI2.

PMID- 29203530
TI  - Visualization of a spinal capillary telangiectasia with 2D DSA and cone-beam CT.

PMID- 29203531
TI  - Editors' Note.

PMID- 29203527
TI  - A novel chemical inducer of Streptococcus quorum sensing acts by inhibiting the
      pheromone-degrading endopeptidase PepO.
AB  - Bacteria produce chemical signals (pheromones) to coordinate behaviors across a
      population in a process termed quorum sensing (QS). QS systems comprising peptide
      pheromones and their corresponding Rgg receptors are widespread among Firmicutes
      and may be useful targets for manipulating microbial behaviors, like suppressing
      virulence. The Rgg2/3 QS circuit of the human pathogen Streptococcus pyogenes
      controls genes affecting resistance to host lysozyme in response to short
      hydrophobic pheromones (SHPs). Considering that artificial activation of a QS
      pathway may be as useful in the objective of manipulating bacteria as inhibiting
      it, we sought to identify small-molecule inducers of the Rgg2/3 QS system. We
      report the identification of a small molecule, P516-0475, that specifically
      induced expression of Rgg2/3-regulated genes in the presence of SHP pheromones at
      concentrations lower than typically required for QS induction. In searching for
      the mode of action of P516-0475, we discovered that an S. pyogenes mutant
      deficient in pepO, a neprilysin-like metalloendopeptidase that degrades SHP
      pheromones, was unresponsive to the compound. P516-0475 directly inhibited
      recombinant PepO in vitro as an uncompetitive inhibitor. We conclude that this
      compound induces QS by stabilizing SHP pheromones in culture. Our study indicates
      the usefulness of cell-based screens that modulate pathway activities to identify
      unanticipated therapeutic targets contributing to QS signaling.

PMID- 29203528
TI  - Elevated sodium chloride drives type I interferon signaling in macrophages and
      increases antiviral resistance.
AB  - Type I IFN production and signaling in macrophages play critical roles in innate
      immune responses. High salt (i.e. high concentrations of NaCl) has been proposed
      to be an important environmental factor that influences immune responses in
      multiple ways. However, it remains unknown whether high salt regulates type I IFN
      production and signaling in macrophages. Here, we demonstrated that high salt
      promoted IFNbeta production and its signaling in both human and mouse
      macrophages, and consequentially primed macrophages for strengthened immune
      sensing and signaling when challenged with viruses or viral nucleic acid
      analogues. Using both pharmacological inhibitors and RNA interference we showed
      that these effects of high salt on IFNbeta signaling were mediated by the p38
      MAPK/ATF2/AP1 signaling pathway. Consistently, high salt increased resistance to
      vesicle stomatitis virus (VSV) infection in vitro. In vivo data indicated that a
      high-salt diet protected mice from lethal VSV infection. Taken together, these
      results identify high salt as a crucial regulator of type I IFN production and
      signaling, shedding important new light on the regulation of innate immune
      responses.

PMID- 29203529
TI  - Crystal and solution structures of human protein-disulfide isomerase-like protein
      of the testis (PDILT) provide insight into its chaperone activity.
AB  - Protein-disulfide isomerase-like protein of the testis (PDILT), a member of the
      protein-disulfide isomerase family, is a chaperone essential for the folding of
      spermatogenesis-specific proteins in male postmeiotic germ cells. However, the
      structural mechanisms that regulate the chaperone function of PDILTs are unknown.
      Here, we report the structures of human PDILT (hPDILT) determined by X-ray
      crystallography to 2.4 A resolution and small-angle X-ray scattering (SAXS).
      Distinct from previously reported U-like structures of related PDI family
      proteins, our structures revealed that hPDILT folds into a compact L-like
      structure in crystals and into an extended chain-like structure in solution. The
      hydrophobic regions and the hydrophobic pockets in hPDILT, which are important
      for substrate recognition, were clearly delineated in the crystal structure.
      Moreover, our results of the SAXS analysis and of structure-based substitutions
      and truncations indicated that the C-terminal tail in hPDILT is required for
      suppression of aggregation of denatured proteins, suggesting that the tail is
      crucial for the chaperone activity of PDILT. Taken together, our findings have
      identified the critical regions and conformational changes of PDILT that enable
      and control its activity. These results advance our understanding of the
      structural mechanisms involved in the chaperone activity of PDILT.

PMID- 29203532
TI  - Letter re: Evaluation of hyperacute infarct volume using ASPECTS and brain CT
      perfusion core volume.

PMID- 29203533
TI  - Letter re: Evaluation of hyperacute infarct volume using ASPECTS and brain CT
      perfusion core volume.

PMID- 29203534
TI  - Author response: Evaluation of hyperacute infarct volume using ASPECTS and brain
      CT perfusion core volume.

PMID- 29203535
TI  - Child Neurology: Primary angiitis of the CNS.

PMID- 29203536
TI  - Teaching NeuroImages: A rare case of giant perivascular spaces in the midbrain
      manifesting as atypical parkinsonism.

PMID- 29203537
TI  - Teaching Video NeuroImages: Epilepsia partialis continua in an adolescent with
      preexisting focal epilepsy.

PMID- 29203538
TI  - High mobility group box 1 orchestrates tissue regeneration via CXCR4.
AB  - Inflammation and tissue regeneration follow tissue damage, but little is known
      about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a
      nuclear protein that, when released on injury, triggers inflammation. We
      previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas
      a disulfide bond makes it a proinflammatory cytokine. Here we report that fully
      reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas
      disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced
      glycation end products) are not involved. Injection of HMGB1 accelerates tissue
      repair by acting on resident muscle stem cells, hepatocytes, and infiltrating
      cells. The nonoxidizable HMGB1 mutant 3S, in which serines replace cysteines,
      promotes muscle and liver regeneration more efficiently than the wild-type
      protein and without exacerbating inflammation by selectively interacting with
      CXCR4. Overall, our results show that the reduced form of HMGB1 coordinates
      tissue regeneration and suggest that 3S may be used to safely accelerate healing
      after injury in diverse clinical contexts.

PMID- 29203539
TI  - Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for
      glioma T cell therapy.
AB  - The median overall survival for children with diffuse intrinsic pontine glioma
      (DIPG) is less than one year. The majority of diffuse midline gliomas, including
      more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to
      methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell
      clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide
      encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR)
      alpha- and beta-chains were cloned into a retroviral vector. TCR-transduced HLA
      A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and
      HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly
      suppressed the progression of glioma xenografts in mice. Alanine-scanning assays
      suggested the absence of known human proteins sharing the key amino acid residues
      required for recognition by the TCR, suggesting that the TCR could be safely used
      in patients. These data provide us with a strong basis for developing T cell
      based therapy targeting this shared neoepitope.

PMID- 29203540
TI  - Toward Tuberculosis Vaccine Development: Recommendations for Nonhuman Primate
      Study Design.
AB  - Clinical trials of novel tuberculosis (TB) vaccines are expensive, while global
      resources for TB vaccine development are limited. Therefore, there is a need for
      robust and predictive preclinical data to support advancement of candidate
      vaccines into clinical trials. Here, we provide a rationale for using the
      nonhuman primate as an essential component of these efforts, as well as guidance
      to the TB community for standardizing experimental design and aligning endpoints
      to facilitate development of new TB vaccines.

PMID- 29203541
TI  - NanI Sialidase Can Support the Growth and Survival of Clostridium perfringens
      Strain F4969 in the Presence of Sialyated Host Macromolecules (Mucin) or Caco-2
      Cells.
AB  - Enterotoxin-producing Clostridium perfringens type A strains cause human
      gastrointestinal (GI) infections, including a very common food poisoning and 5 to
      10% of all cases of antibiotic-associated diarrhea. This bacterium can utilize
      free sialic acid for growth, but most sialic acids in the GI tract are
      sequestered on macromolecules, such as the mucin proteins of mucus or
      glycoconjugates in host cells. However, many C. perfringens strains produce
      sialidases that might promote growth and survival by generating free sialic acid
      from those sialyated host macromolecules or by exposing underlying carbohydrates
      or proteins for digestion by other enzymes. The current study tested that
      possibility and found that the C. perfringens nonfoodborne human GI disease
      strain F4969 can use either a mucin preparation or Caco-2 cells, which are human
      enterocyte-like cells, to support its growth and survival. An isogenic nanI null
      mutant and complemented strain were used to show that this enhanced growth and
      survival using mucin or Caco-2 cells involved NanI, which is the major
      exosialidase of F4969 and many other C. perfringens strains. Experiments also
      suggested that, at least in part, this growth promotion involves utilization of
      NanI-generated sialic acid. In addition, a sialidase inhibitor named siastatin B
      reduced the growth and survival of F4969 growing with either the mucin
      preparation or Caco-2 cells. These findings suggest that, when produced, NanI may
      be a significant contributor to C. perfringens human GI infections by promoting
      the intestinal growth and survival of this bacterium. They also suggest the
      possibility that sialidase inhibitors might inhibit C. perfringens infections.

PMID- 29203542
TI  - Proinflammatory Role of Monocyte-Derived CX3CR1int Macrophages in Helicobacter
      hepaticus-Induced Colitis.
AB  - Cells of the monocyte/macrophage lineage play important roles in the pathogenesis
      of inflammatory bowel diseases, but they are also present in the normal healthy
      intestine, where they are critical for maintaining homeostasis. It has been
      unclear whether the proinflammatory roles of intestinal macrophages reflect
      altered behavior of the existing resident cells, or whether they involve
      recruitment of a distinct cell type. Here, we have explored these ideas using the
      model of colitis induced by Helicobacter hepaticus in the context of
      neutralization or deletion of interleukin-10 (IL-10). Granulocytes and monocytes
      made up most of the inflammatory myeloid infiltrates found in the colon of H.
      hepaticus-infected colitic mice, rising to a peak within 2 weeks of H. hepaticus
      inoculation but taking several months to resolve completely. The inflammatory
      response was dependent on the combined presence of H. hepaticus and absence of IL
      10 and was accompanied by increased production of inflammatory mediators such as
      IL-1beta, tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-23p19 by
      infiltrating myeloid cells, mostly relatively immature cells of the macrophage
      lineage that express intermediate levels of CX3CR1. In contrast, the population
      of mature CX3CR1hi macrophages did not expand as markedly during colitis, and
      these cells made little contribution to inflammatory mediator production. Taking
      into account their numerical dominance in the myeloid compartment, we conclude
      that newly recruited monocytes are the main source of proinflammatory mediators
      in colitis induced in the absence of IL-10 signaling and that altered behavior of
      mature macrophages is not a major component of this pathology.

PMID- 29203543
TI  - Novel Mechanism behind the Immunopathogenesis of Vulvovaginal Candidiasis:
      "Neutrophil Anergy".
AB  - For over 3 decades, investigators have studied the pathogenesis of vulvovaginal
      candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal
      models. While there was considerable consensus that susceptibility was not
      associated with any apparent deficiencies in adaptive immunity, protective immune
      mechanisms and the role of innate immunity remained elusive. It was not until an
      innovative live-challenge design was conducted in women that a fuller
      understanding of the natural history of infection/disease was achieved. These
      studies revealed that symptomatic infection is associated with recruitment of
      polymorphonuclear neutrophils (PMNs) into the vaginal lumen. Subsequent studies
      in the established mouse model demonstrated that infiltrating PMNs were incapable
      of reducing the fungal burden, which supported the hypothesis that VVC/RVVC was
      an immunopathology, whereby Candida and the host response drive symptomatic
      disease. Further studies in mice revealed the requirement for C. albicans hyphae
      and identified pattern recognition receptors (PRRs) and proinflammatory mediators
      responsible for the PMN response, all of which are critical pieces of the
      immunopathogenesis. However, a mechanism explaining PMN dysfunction at the
      vaginal mucosa remained an enigma. Ultimately, by employing mouse strains
      resistant or susceptible to chronic VVC, it was determined that heparan sulfate
      (HS) in the vaginal environment of susceptible mice serves as a competitive
      ligand for Mac-1 on PMNs, which effectively renders the PMNs incapable of binding
      to Candida to initiate killing. Hence, the outcome of symptomatic VVC/RVVC is
      postulated to be dependent on a PMN-mediated immunopathogenic response involving
      HS that effectively places the neutrophils in a state of functional anergy.

PMID- 29203544
TI  - Mapping Protective Regions on a Three-Dimensional Model of the Moraxella
      catarrhalis Vaccine Antigen Oligopeptide Permease A.
AB  - A vaccine against Moraxella catarrhalis would reduce tremendous morbidity,
      mortality, and financial burden by preventing otitis media in children and
      exacerbations of chronic obstructive pulmonary disease (COPD) in adults.
      Oligopeptide permease A (OppA) is a candidate vaccine antigen that is (i) a
      nutritional virulence factor expressed on the bacterial cell surface during
      infection, (ii) widely conserved among strains, (iii) highly immunogenic, and
      (iv) a protective antigen based on its capacity to induce protective responses in
      immunized animals. In the present study, we show that the antibodies to OppA
      following vaccination mediate accelerated clearance in animals after pulmonary
      challenge. To identify regions of OppA that bind protective antibodies, truncated
      constructs of OppA were engineered and studied to map regions of OppA with
      surface-accessible epitopes that bind high-avidity antibodies following
      vaccination. Protective epitopes were located in the N and C termini of the
      protein. Immunization of mice with constructs corresponding to these regions (T5
      and T8) induced protective responses. Studies of overlapping peptide libraries of
      constructs T5 and T8 with OppA immune serum identified two discrete regions on
      each construct. These potentially protective regions were mapped on a three
      dimensional computational model of OppA, where regions with solvent-accessible
      amino acids were identified as three potentially protective epitopes. In all,
      these studies revealed two regions with three specific epitopes in OppA that
      induce potentially protective antibody responses following vaccination. Detection
      of antibodies to these regions could serve to guide vaccine formulation and as a
      diagnostic tool for monitoring development of protective responses during
      clinical trials.

PMID- 29203545
TI  - Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of
      Bronchial Epithelial Layers.
AB  - The airway epithelium restricts the penetration of inhaled pathogens into the
      underlying tissue and plays a crucial role in the innate immune defense against
      respiratory infections. The whooping cough agent, Bordetella pertussis, adheres
      to ciliated cells of the human airway epithelium and subverts its defense
      functions through the action of secreted toxins and other virulence factors. We
      examined the impact of B. pertussis infection and of adenylate cyclase toxin
      hemolysin (CyaA) action on the functional integrity of human bronchial epithelial
      cells cultured at the air-liquid interface (ALI). B. pertussis adhesion to the
      apical surface of polarized pseudostratified VA10 cell layers provoked a
      disruption of tight junctions and caused a drop in transepithelial electrical
      resistance (TEER). The reduction of TEER depended on the capacity of the secreted
      CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl
      cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a
      decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused
      actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin
      6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8
      chemokine and of the antimicrobial peptide beta-defensin 2. These results
      indicate that CyaA toxin activity compromises the barrier and innate immune
      functions of Bordetella-infected airway epithelia.

PMID- 29203546
TI  - Use of Proteins Identified through a Functional Genomic Screen To Develop a
      Protein Subunit Vaccine That Provides Significant Protection against Virulent
      Streptococcus suis in Pigs.
AB  - Streptococcus suis is a bacterium that is commonly carried in the respiratory
      tract and that is also one of the most important invasive pathogens of swine,
      commonly causing meningitis, arthritis, and septicemia. Due to the existence of
      many serotypes and a wide range of immune evasion capabilities, efficacious
      vaccines are not readily available. The selection of S. suis protein candidates
      for inclusion in a vaccine was accomplished by identifying fitness genes through
      a functional genomics screen and selecting conserved predicted surface-associated
      proteins. Five candidate proteins were selected for evaluation in a vaccine trial
      and administered both intranasally and intramuscularly with one of two different
      adjuvant formulations. Clinical protection was evaluated by subsequent intranasal
      challenge with virulent S. suis While subunit vaccination with the S. suis
      proteins induced IgG antibodies to each individual protein and a cellular immune
      response to the pool of proteins and provided substantial protection from
      challenge with virulent S. suis, the immune response elicited and the degree of
      protection were dependent on the parenteral adjuvant given. Subunit vaccination
      induced IgG reactive against different S. suis serotypes, indicating a potential
      for cross protection.

PMID- 29203547
TI  - Regulated release of cryptococcal polysaccharide drives virulence and suppresses
      immune infiltration into the central nervous system.
AB  - Cryptococcus neoformans is a common environmental yeast and opportunistic
      pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality
      primarily results from meningoencephalitis, which occurs when fungal cells
      disseminate to the brain from the initial pulmonary infection site. A key C.
      neoformans virulence trait is the polysaccharide capsule. Capsule shields C.
      neoformans from immune-mediated recognition and destruction. The main capsule
      component, glucuronoxylomannan (GXM), is found both attached to the cell surface
      and free in the extracellular space (as exo-GXM). Exo-GXM accumulates in patient
      serum and cerebrospinal fluid at MUg/mL concentrations, has well-documented
      immunosuppressive properties, and correlates with poor patient outcomes. However,
      it is poorly understood whether exo-GXM release is regulated or the result of
      shedding during normal capsule turnover. We demonstrate that exo-GXM release is
      regulated by environmental cues and inversely correlates with surface capsule
      levels. We identified genes specifically involved in exo-GXM release that do not
      alter surface capsule thickness. The first mutant, liv7Delta, released less GXM
      than wild-type cells when capsule is not induced. The second mutant,
      cnag_00658Delta, released more exo-GXM under capsule-inducing conditions. Exo-GXM
      release observed in vitro correlated with polystyrene adherence, virulence, and
      fungal burden during murine infection. Additionally, we find that exo-GXM reduces
      cell size and capsule thickness in capsule-inducing conditions, potentially
      influencing dissemination. Finally, we demonstrated that exo-GXM prevents immune
      cell infiltration into the brain during disseminated infection and highly
      inflammatory intracranial infection. Our data suggest that exo-GXM performs a
      different role from capsule GXM during infection, altering cell size and
      suppressing inflammation.

PMID- 29203548
TI  - Utilization of host polyamines in alternatively activated macrophages promotes
      chronic infection by Brucella abortus.
AB  - Treatment of intracellular bacterial pathogens with antibiotic therapy often
      requires a long course of multiple antibiotics. A barrier to developing
      strategies that enhance antibiotic efficacy against these pathogens is our poor
      understanding of the intracellular nutritional environment that maintains
      bacterial persistence. The intracellular pathogen Brucella abortus survives and
      replicates preferentially in alternatively activated macrophages (AAM), however
      knowledge of the metabolic adaptations promoting exploitation of this niche is
      limited. Here we show that one mechanism promoting enhanced survival in AAM is a
      shift in macrophage arginine utilization from production of nitric oxide (NO) to
      biosynthesis of polyamines, induced by IL-4/IL-13 treatment. B. abortus is unable
      to synthesize polyamines, however production of polyamines by infected AAM
      promoted both intracellular survival of bacteria and chronic infection in mice,
      as inhibition of macrophage polyamine synthesis or inactivation of the B. abortus
      putrescine transporter potIHGF reduced both intracellular survival in AAM and
      persistence in mice. These results demonstrate that increased intracellular
      availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced
      AAM promotes chronic persistence of B. abortus within this niche and suggest that
      targeting of this pathway may aid in eradicating chronic infection.

PMID- 29203549
TI  - Adapting QOF to focus on wellbeing and health.

PMID- 29203550
TI  - Basic Review of Radiation Biology and Terminology.
AB  - The purpose of this paper is to review basic radiation biology and associated
      terminology to impart a better understanding of the importance of basic concepts
      of ionizing radiation interactions with living tissue. As health care workers in
      a field that utilizes ionizing radiation, nuclear medicine technologists are
      concerned about the possible acute and chronic effects of occupational radiation
      exposure. Technologists should have a clear understanding of what they are
      exposed to and how their safety could be affected. Furthermore, technologists
      should be knowledgeable about radiation effects so that they can adequately
      assuage possible patient fears about undergoing a nuclear medicine procedure.
      After reading this article, the nuclear medicine technologist will be familiar
      with basic radiation biology concepts; types of interactions of radiation with
      living tissue, and possible effects from that exposure; theoretic dose-response
      curves and how they are used in radiation biology; stochastic versus
      nonstochastic effects of radiation exposure, and what these terms mean in
      relation to both high- and low-dose radiation exposure; and possible acute and
      chronic radiation exposure effects.

PMID- 29203551
TI  - Erratum.

PMID- 29203552
TI  - Thanks to All Who Make This Journal Possible.

PMID- 29203553
TI  - The New SNMMI-TS Strategic Plan: Establishing a Firm Foundation for the Future.

PMID- 29203554
TI  - The clinical and prognostic relevance of driver mutations in 203 Taiwanese
      patients with primary myelofibrosis.
AB  - AIMS: We investigated the clinical and prognostic relevance of the mutational
      status of driver genes with allele burden and endogenous erythroid colony (EEC)
      growth in 203 Taiwanese patients with primary myelofibrosis (PMF). METHODS:
      Pyrosequencing was used to detect JAK2V617F mutational status and measure allele
      burden, while MPL (exon 10) mutations were analysed by PCR assay and then by
      direct sequencing. CALR exon 9 mutations were first screened for length changes
      by GeneScan followed by sequencing. The allele burden of the mutated CALR gene
      was measured by pyrosequencing. The EEC assay was conducted using a serum-free
      culture system. RESULTS: The frequencies of the three driver mutations and triple
      negative status were similarly distributed between pre-PMF and overt PMF
      patients, except that pre-PMF patients had a higher incidence of CALR type 2/type
      2 like mutations and a lower JAK2V617F allele burden. EEC growth and CALR
      mutations conferred favourable overall survival (OS). A lower JAK2V617F allele
      burden and grade 3 bone marrow fibrosis were associated with shorter OS and
      decreased leukaemia-free survival (LFS). Type 2/type 2-like CAL mutations were
      associated with better LFS compared with type1/type 1-like mutations. Patients
      with triple-negative mutation status had significantly worse OS and LFS. The
      allele burden of CALR mutations remained unchanged, while some JAK2V617F
      mutations showed clonal expansion in patients during secondary acute myeloid
      leukaemia transformation. CONCLUSIONS: Our study showed that EEC growth, a higher
      JAK2V617F allele burden and CALR mutations, especially type 2, were independent
      predictors for better outcomes in PMF. The allele burden of CALR mutations
      remained stable, but the allele burden of JAK2V617Fmutations was variable during
      leukaemia transformation.

PMID- 29203555
TI  - Physical activity investments that work-Get Scotland walking: a National Walking
      Strategy for Scotland.

PMID- 29203556
TI  - NDH-PSI Supercomplex Assembly Precedes Full Assembly of the NDH Complex in
      Chloroplast.
AB  - The chloroplast NADH dehydrogenase-like (NDH) complex is structurally similar to
      respiratory complex I and mediates PSI cyclic electron flow. In Arabidopsis
      (Arabidopsis thaliana), chloroplast NDH is composed of at least 29 subunits and
      associates with two copies of PSI to form the NDH-PSI supercomplex. Here, we
      found that CHLORORESPIRATORY REDUCTION3 (CRR3) is an assembly factor required for
      the accumulation of subcomplex B (SubB) of chloroplast NDH. In Suc density
      gradient centrifugation, CRR3 was detected in three protein complexes.
      Accumulation of the largest peak III complex was impaired in mutants defective in
      the SubB subunits PnsB2-PnsB5. The oligomeric form of CRR3 likely functions to
      assemble the core of SubB to form the peak III complex as an assembly
      intermediate. A defect in the PnsL3 subunit increased the level of the peak III
      complex, suggesting that CRR3 was released from the assembly intermediate after
      PnsL3 binding. Unlike PnsB2-PnsB5 and PnsL3, PnsB1 was not absolutely necessary
      for stabilizing SubB. PnsB1 is likely incorporated into the intermediate at the
      final step during SubB assembly. Lhca6 is a linker protein mediating NDH-PSI
      supercomplex formation, and its site of contact with NDH was suggested to be
      SubB. In the lhca6 mutant, accumulation of the peak III complex was impaired,
      suggesting that SubB interacted with Lhca6 during the step of SubB assembly. The
      process of supercomplex formation was triggered before the completion of the NDH
      assembly. Consistent with its predicted function, CRR3 accumulated in young
      leaves, where the NDH complex was assembled.

PMID- 29203557
TI  - A Single Oxidosqualene Cyclase Produces the Seco-Triterpenoid alpha-Onocerin.
AB  - 8,14-seco-Triterpenoids are characterized by their unusual open C-ring. Their
      distribution in nature is rare and scattered in taxonomically unrelated plants.
      The 8,14-seco-triterpenoid alpha-onocerin is only known from the evolutionarily
      distant clubmoss genus Lycopodium and the leguminous genus Ononis, which makes
      the biosynthesis of this seco-triterpenoid intriguing from an evolutionary
      standpoint. In our experiments with Ononis spinosa, alpha-onocerin was detected
      only in the roots. Through transcriptome analysis of the roots, an oxidosqualene
      cyclase, OsONS1, was identified that produces alpha-onocerin from squalene
      2,3;22,23-dioxide when transiently expressed in Nicotiana bethamiana In contrast,
      in Lycopodium clavatum, two sequential cyclases, LcLCC and LcLCD, are required to
      produce alpha-onocerin in the N. benthamiana transient expression system.
      Expression of OsONS1 in the lanosterol synthase knockout yeast strain GIL77,
      which accumulates squalene-2,3;22,23-dioxide, verified the alpha-onocerin
      production. A phylogenetic analysis predicts that OsONS1 branches off from
      specific lupeol synthases and does not group with the known L. clavatum alpha
      onocerin cyclases. Both the biochemical and phylogenetic analyses of OsONS1
      suggest convergent evolution of the alpha-onocerin pathways. When OsONS1 was
      coexpressed in N. benthamiana leaves with either of the two O. spinosa squalene
      epoxidases, OsSQE1 or OsSQE2, alpha-onocerin production was boosted, most likely
      because the epoxidases produce higher amounts of squalene-2,3;22,23-dioxide.
      Fluorescence lifetime imaging microscopy analysis demonstrated specific protein
      protein interactions between OsONS1 and both O. spinosa squalene epoxidases.
      Coexpression of OsONS1 with the two OsSQEs suggests that OsSQE2 is the preferred
      partner of OsONS1 in planta. Our results provide an example of the convergent
      evolution of plant specialized metabolism.

PMID- 29203558
TI  - SEIPIN Proteins Mediate Lipid Droplet Biogenesis to Promote Pollen Transmission
      and Reduce Seed Dormancy.
AB  - Lipid droplets (LDs) are ubiquitous organelles in plant cells, but their
      physiological roles are largely unknown. To gain insight into the function of LDs
      in plants, we have characterized the Arabidopsis homologs of SEIPIN proteins,
      which are crucial factors for LD biogenesis in yeast and animals. SEIPIN1 is
      expressed almost exclusively in embryos, while SEIPIN2 and SEIPIN3 have broader
      expression profiles with maximal levels in embryos and pollen, where LDs
      accumulate most abundantly. Genetic analysis demonstrates that all three SEIPINs
      contribute to proper LD biogenesis in embryos, whereas in pollen, only SEIPIN2
      and SEIPIN3 play a significant role. The double seipin2 seipin3 and triple seipin
      mutants accumulate extremely enlarged LDs in seeds and pollen, which hinders
      their subsequent mobilization during germination. Interestingly, electron
      microscopy analysis reveals the presence of nuclear LDs attached to type I
      nucleoplasmic reticulum in triple seipin mutant embryos, supporting that SEIPINs
      are essential for maintaining the correct polarity of LD budding at the nuclear
      envelope, restricting it to the outer membrane. In pollen, the perturbations in
      LD biogenesis and turnover are coupled to reduced germination in vitro and with
      lower fertilization efficiency in vivo. In seeds, germination per se is not
      affected in seipin2 seipin3 and triple seipin mutants, but there is a striking
      increase in seed dormancy levels. Our findings reveal the relevance of SEIPIN
      dependent LD biogenesis in pollen transmission and in adjusting the timing of
      seed germination, two key adaptive traits of great importance in agriculture.

PMID- 29203561
TI  - Correction to: Symptom Diary Use and Improved Survival for Patients With Heart
      Failure.

PMID- 29203559
TI  - Membrane Dynamics and Multiple Functions of Oil Bodies in Seeds and Leaves.

PMID- 29203560
TI  - Roles for Light, Energy, and Oxygen in the Fate of Quiescent Axillary Buds.

PMID- 29203563
TI  - Detection of Urinary Mulberry Bodies Leads to Diagnosis of Fabry Cardiomyopathy:
      A Simple Clue in the Urine Sediment.

PMID- 29203564
TI  - Learning From Major Clinical Trials: Bending Without Breaking.

PMID- 29203562
TI  - Impaired Protein Quality Control During Left Ventricular Remodeling in Mice With
      Cardiac Restricted Overexpression of Tumor Necrosis Factor.
AB  - BACKGROUND: Sustained inflammation in the heart is sufficient to provoke left
      ventricular dysfunction and left ventricular remodeling. Although inflammation
      has been linked to many of the biological changes responsible for adverse left
      ventricular remodeling, the relationship between inflammation and protein quality
      control in the heart is not well understood. METHODS AND RESULTS: To study the
      relationship between chronic inflammation and protein quality control, we used a
      mouse model of dilated cardiomyopathy driven by cardiac restricted overexpression
      of TNF (tumor necrosis factor; Myh6-sTNF). Myh6-sTNF mice develop protein
      aggregates containing ubiquitin-tagged proteins within cardiac myocytes related
      to proteasome dysfunction and impaired autophagy. The 26S proteasome was
      dysfunctional despite normal function of the core 20S subunit. We found an
      accumulation of autophagy substrates in Myh6-sTNF mice, which were also seen in
      tissue from patients with end-stage heart failure. Moreover, there was evidence
      of impaired autophagosome clearance after chloroquine administration in these
      mice indicative of impaired autophagic flux. Finally, there was increased
      mammalian target of rapamycin complex 1 (mTORC1) activation, which has been
      linked to inhibition of both the proteasome and autophagy. CONCLUSIONS: Myh6-sTNF
      mice with sustained inflammatory signaling develop proteasome dysfunction and
      impaired autophagic flux that is associated with enhanced mTORC1 activation.

PMID- 29203565
TI  - The Tale of an Innocent: Intensive Treatment and the J-Curve in the SPRINT Trial
      (Systolic Blood Pressure Intervention Trial).

PMID- 29203566
TI  - Echocardiographic Detection of Latent Rheumatic Heart Disease: A Pandora's Box?

PMID- 29203567
TI  - FUNDC1: A Novel Protein in Cardiac Health.

PMID- 29203568
TI  - Increased Inflammation in Pericardial Fluid Persists 48 Hours After Cardiac
      Surgery.

PMID- 29203569
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Genotype-Phenotype Correlation
      of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of
      Probands With Brugada Syndrome: A Japanese Multicenter Registry".

PMID- 29203570
TI  - Response by Yamagata et al to Letter Regarding Article, "Genotype-Phenotype
      Correlation of SCN5A Mutation for the Clinical and Electrocardiographic
      Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter
      Registry".

PMID- 29203571
TI  - Letter by Kotsiou and Gourgoulianis Regarding Article, "Pathophysiology of
      Takotsubo Syndrome".

PMID- 29203572
TI  - Letter by Stiermaier and Eitel Regarding Article, "Pathophysiology of Takotsubo
      Syndrome".

PMID- 29203573
TI  - Mechanisms of beta-cell dedifferentiation in diabetes: recent findings and future
      research directions.
AB  - Like all the cells of an organism, pancreatic beta-cells originate from embryonic
      stem cells through a complex cellular process termed differentiation.
      Differentiation involves the coordinated and tightly controlled
      activation/repression of specific effectors and gene clusters in a time-dependent
      fashion thereby giving rise to particular morphological and functional cellular
      features. Interestingly, cellular differentiation is not a unidirectional
      process. Indeed, growing evidence suggests that under certain conditions, mature
      beta-cells can lose, to various degrees, their differentiated phenotype and
      cellular identity and regress to a less differentiated or a precursor-like state.
      This concept is termed dedifferentiation and has been proposed, besides cell
      death, as a contributing factor to the loss of functional beta-cell mass in
      diabetes. beta-cell dedifferentiation involves: (1) the downregulation of beta
      cell-enriched genes, including key transcription factors, insulin, glucose
      metabolism genes, protein processing and secretory pathway genes; (2) the
      concomitant upregulation of genes suppressed or expressed at very low levels in
      normal beta-cells, the beta-cell forbidden genes; and (3) the likely upregulation
      of progenitor cell genes. These alterations lead to phenotypic reconfiguration of
      beta-cells and ultimately defective insulin secretion. While the major role of
      glucotoxicity in beta-cell dedifferentiation is well established, the precise
      mechanisms involved are still under investigation. This review highlights the
      identified molecular mechanisms implicated in beta-cell dedifferentiation
      including oxidative stress, endoplasmic reticulum (ER) stress, inflammation and
      hypoxia. It discusses the role of Foxo1, Myc and inhibitor of differentiation
      proteins and underscores the emerging role of non-coding RNAs. Finally, it
      proposes a novel hypothesis of beta-cell dedifferentiation as a potential
      adaptive mechanism to escape cell death under stress conditions.

PMID- 29203574
TI  - Blunt chest trauma: a clinical chameleon.
AB  - The incidence of blunt chest trauma (BCT) is greater than 15% of all trauma
      admissions to the emergency departments worldwide and is the second leading cause
      of death after head injury in motor vehicle accidents. The mortality due to BCT
      is inhomogeneously described ranging from 9% to 60%. BCT is commonly caused by a
      sudden high-speed deceleration trauma to the anterior chest, leading to a
      compression of the thorax. All thoracic structures might be injured as a result
      of the trauma. Complex cardiac arrhythmia, heart murmurs, hypotension, angina
      like chest pain, respiratory insufficiency or distention of the jugular veins may
      indicate potential cardiac injury. However, on admission to emergency departments
      symptoms might be missing or may not be clearly associated with the injury.
      Accurate diagnostics and early management in order to prevent serious
      complications and death are essential for patients suffering a BCT. Optimal
      initial diagnostics includes echocardiography or CT, Holter-monitor recordings,
      serial 12-lead electrocardiography and measurements of cardiac enzymes. Immediate
      diagnostics leading to the appropriate therapy is essential for saving a
      patient's life. The key aspect of the entire management, including diagnostics
      and treatment of patients with BCT, remains an interdisciplinary team involving
      cardiologists, cardiothoracic surgeons, imaging radiologists and trauma
      specialists working in tandem.

PMID- 29203575
TI  - Chronic Delta9-THC in Rhesus Monkeys: Effects on Cognitive Performance and
      Dopamine D2/D3 Receptor Availability.
AB  - Cannabis-related impairments to cognitive function may represent novel
      therapeutic targets for cannabis-use disorder, although the nature, persistence,
      and reversibility of such deficits remain unclear. Adult male rhesus monkeys (N =
      6) responded in the morning on tasks designed to assess different cognitive
      domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB)
      touchscreens followed by responding maintained under a fixed-ratio (FR) 10
      schedule of food presentation in different operant chambers. First, the acute
      effects of Delta9-tetrahydrocannabinol (THC; 0.01-0.56 mg/kg, i.v.) on cognitive
      performance, FR responding, and body temperature were determined. Next, THC (1.0
      2.0 mg/kg, s.c.) was administered daily after FR 10 sessions for 12 weeks, during
      which the residual effects of THC (i.e., 22 hours after administration) on
      cognition were examined and the acute effects of THC were redetermined. In a
      subgroup of monkeys, dopamine D2/D3 receptor availability was assessed after 4
      weeks of chronic THC exposure and compared with drug-naive controls using
      positron emission tomography and [11C]-raclopride (N = 4/group). Acute THC
      pretreatments dose-dependently decreased FR responding and body temperature, and
      impairment to cognitive performance was task specific. During chronic treatment,
      THC produced persistent residual impairment only to working memory; tolerance
      differentially developed to acute cognitive impairments. There was recovery from
      residual cognitive impairments to working memory within 2 weeks of abstinence.
      Compared with controls, D2/D3 receptor availability was not altered during
      chronic THC treatment. In conclusion, THC-induced disruptions in cognition were
      task-specific, as was tolerance development, and not related to changes in D2/D3
      receptor availability. Intervention strategies for cannabis-use disorder that
      enhance working memory performance may facilitate positive treatment outcomes.

PMID- 29203577
TI  - HIV and herpes simplex virus type 2 epidemiological synergy: misguided
      observational evidence? A modelling study.
AB  - OBJECTIVES: To investigate whether observational studies of HIV and herpes
      simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2
      epidemiological synergy. METHODS: An individual-based Monte Carlo model was used
      to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological
      interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional
      observational studies were simulated by sampling individuals from the population
      to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta
      analyses were conducted to estimate the pooled mean ORs. Impact of under
      reporting of sexual behaviour and miscapture of high-risk individuals was
      assessed through sensitivity analyses. RESULTS: Assuming no HIV/HSV-2 biological
      interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled
      mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners
      over last year, over lifetime and for both partner numbers simultaneously reduced
      the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54
      (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction,
      the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI
      7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90),
      3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under
      reporting of partners reduced the confounder-adjustment effects. Miscapture of
      high-risk individuals considerably lowered the estimated ORs. CONCLUSIONS: It is
      difficult to control for sexual-behaviour confounding in observational studies.
      The observed HIV/HSV-2 association appears more consistent with two infections
      sharing the same mode of transmission, rather than with HSV-2 enhancing HIV
      acquisition.

PMID- 29203576
TI  - Dimethoxy-etomidate: A Nonhypnotic Etomidate Analog that Potently Inhibits
      Steroidogenesis.
AB  - Cushing's syndrome is characterized by the overproduction of adrenocortical
      steroids. Steroidogenesis inhibitors are mainstays of medical therapy for
      Cushing's syndrome; unfortunately, adverse side effects and treatment failures
      are common with currently available drugs. The general anesthetic induction agent
      etomidate is among the most potent inhibitors of adrenocortical steroidogenesis.
      However, its use as a treatment of Cushing's syndrome is complicated by its
      sedative-hypnotic activity and ability to produce myoclonus, central nervous
      system actions thought to be mediated by the GABAA receptor. Here, we describe
      the pharmacology of the novel etomidate analog (R)-ethyl 1-(1-(3,5
      dimethoxyphenyl)ethyl)-1H-imidazole-5-carboxylate (dimethoxy-etomidate). In
      contrast to etomidate, dimethoxy-etomidate minimally enhanced GABA-evoked GABAA
      receptor-mediated currents even at a near-saturating aqueous concentration. In
      Sprague-Dawley rats, dimethoxy-etomidate's potency for producing loss of righting
      reflexes-an animal model of sedation/hypnosis-was 2 orders of magnitude lower
      than that of etomidate, and it did not produce myoclonus. However, similar to
      etomidate, dimethoxy-etomidate potently suppressed adrenocortical steroid
      synthesis primarily by inhibiting 11beta-hydroxylase. [3H]etomidate binding to
      rat adrenocortical membranes was inhibited by dimethoxy-etomidate in a biphasic
      manner with IC50 values of 8.2 and 3970 nM, whereas that by etomidate was
      monophasic with an IC50 of 22 nM. Our results demonstrate that, similar to
      etomidate, dimethoxy-etomidate potently and dose-dependently suppresses
      adrenocortical steroid synthesis by inhibiting 11beta-hydroxylase. However, it is
      essentially devoid of etomidate's GABAA receptor positive modulatory and sedative
      hypnotic activities and produces no myoclonus, providing proof of concept for the
      design of etomidate analogs without important central nervous system actions for
      the pharmacologic treatment of Cushing's syndrome.

PMID- 29203578
TI  - Left Ventricular Thrombi in Takotsubo Syndrome: Incidence, Predictors, and
      Management: Results From the GEIST (German Italian Stress Cardiomyopathy)
      Registry.
AB  - BACKGROUND: Left ventricular (LV) thrombi during Takotsubo syndrome represent a
      potential complication and can be associated with cerebrovascular embolic events.
      The aim of this study was to evaluate the exact incidence, predictors, and
      management strategies of LV thrombi in patients with Takotsubo syndrome. METHODS
      AND RESULTS: We enrolled 541 consecutive patients in a multicenter international
      registry. Clinical features and echocardiographic data at admission, during
      hospitalization, and after 3 months were evaluated. Survival rates for long-term
      follow-up (mean 984+/-908 days) were recorded. Twelve Takotsubo syndrome patients
      (2.2%) developed LV thrombi (all female presenting with apical ballooning
      pattern). All patients with LV thrombi were treated with oral anticoagulation
      therapy; however, 2 (17%) had a stroke before treatment initiation. These
      patients were characterized by a higher prevalence of ST-elevation (56% versus
      16%; P<0.001) and higher troponin I levels (10.8+/-18.3 ng/mL versus 3.5+/-4.3
      ng/mL; P=0.001) as compared with those without LV thrombi. At multivariate
      analysis including age, sex, LV ejection fraction, ST-elevation at admission, and
      apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for
      LV thrombosis (hazard ratio 6.6, confidence interval, 1.01-40.0; P=0.04). After 3
      months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted
      in all patients except 1. At long-term follow-up, the survival rate was not
      different between patients with and without LV thrombi (84% versus 85%; P=0.99).
      CONCLUSIONS: LV thrombi have a relatively low incidence among patients with
      Takotsubo syndrome and were detected in female patients with apical ballooning
      pattern and increased troponin levels. Oral anticoagulation therapy for 3 months
      seems reasonable in these high-risk patients.

PMID- 29203579
TI  - Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain
      Natriuretic Peptide.
AB  - BACKGROUND: Besides the relevant role of brain-type natriuretic peptide (BNP) as
      biomarker of cardioembolic strokes, new experimental evidences suggest that this
      peptide may mediate neuroprotective effects. In this study, we have evaluated for
      the first time the clinical association between BNP (by means of proBNP) and good
      outcome in ischemic stroke patients, and analyzed the effect of blood BNP
      increase in an ischemic animal model. METHODS AND RESULTS: A retrospective study
      with 2 different cohorts (262 patients in cohort I and 610 in cohort II) from the
      same prospective stroke registry was performed. proBNP concentration was analyzed
      within the first 12 hours from stroke onset. The primary predictor variable was
      functional outcome evaluated by modified Rankin Scale at 3 months. For the
      experimental study, BNP pretreatment was tested in an ischemic animal model
      subjected to a transient occlusion of the cerebral artery, and the infarct volume
      and sensorimotor deficit were evaluated for 14 days. Cardioembolic strokes
      presented a positive correlation between proBNP concentration and modified Rankin
      Scale at 3 months; however, noncardioembolic strokes presented a negative
      correlation. In the logistic regression analysis, noncardioembolic strokes with
      concentrations of proBNP >=340 pg/mL were associated with a good outcome. In line
      with these clinical findings, the experimental study revealed that those BNP
      pretreated animals presented a reduction on infarct volumes at 24 hours and
      functional recovery at days 7 and 14 compared with the control groups.
      CONCLUSIONS: These clinical and experimental evidences support the potential role
      of BNP as a protective factor against cerebral ischemia.

PMID- 29203580
TI  - Thrombocytopenia as a Preoperative Risk Assessment Tool in Patients With
      Rheumatic Heart Disease Undergoing Valve Replacement Surgery.
AB  - BACKGROUND: Postoperative thrombocytopenia has been reported to be correlated
      with adverse events, but the prognostic value of baseline thrombocytopenia is
      unclear. This study was undertaken to evaluate the relationship between
      preoperative thrombocytopenia and adverse outcomes in patients with rheumatic
      heart disease who underwent valve replacement surgery. METHODS AND RESULTS: A
      total of 1789 patients with rheumatic heart disease undergoing valve replacement
      surgery were consecutively enrolled and postoperatively followed up for 1 year.
      Patients were stratified on the basis of presence (n=495) or absence (n=1294) of
      thrombocytopenia (platelet count, <150*109/L), according to hospital admission
      platelet counts. During the hospitalization period, 69 patients (3.9%) died. The
      in-hospital all-cause mortality rate was significantly higher in the
      thrombocytopenic group (6.9% versus 2.7%; P<0.001). Multivariate analyses
      revealed that thrombocytopenia was independently associated with in-hospital all
      cause mortality (odds ratio, 2.21; 95% confidence interval, 1.29-3.80; P=0.004).
      Platelet counts could predict in-hospital all-cause mortality for patients both
      with and without previous atrial fibrillation (areas under the curve, 0.708
      [P<0.001] and 0.610 [P=0.025], respectively). One-year survival was significantly
      lower in patients with thrombocytopenia compared with controls (91.3% versus
      96.1%; log-rank=14.65; P<0.001). In addition, thrombocytopenia was an independent
      predictor for postoperative 1-year all-cause mortality in multivariate Cox
      regression analysis. CONCLUSIONS: Platelet counts, as simple and inexpensive
      indexes, were reliable to be used as a preoperative risk assessment tool for
      patients with rheumatic heart disease undergoing valve replacement surgery.

PMID- 29203582
TI  - Morning Enzymatic Activity of DPP-4 Is Differentially Altered by Sleep Loss in
      Women and Men.

PMID- 29203581
TI  - Cardiac Insulin Signaling Regulates Glycolysis Through Phosphofructokinase 2
      Content and Activity.
AB  - BACKGROUND: The healthy heart has a dynamic capacity to respond and adapt to
      changes in nutrient availability. Diabetes mellitus disrupts this metabolic
      flexibility and promotes cardiomyopathy through mechanisms that are not
      completely understood. Phosphofructokinase 2 (PFK-2) is a primary regulator of
      cardiac glycolysis and substrate selection, yet its regulation under normal and
      pathological conditions is unknown. This study was undertaken to determine how
      changes in insulin signaling affect PFK-2 content, activity, and cardiac
      metabolism. METHODS AND RESULTS: Streptozotocin-induced diabetes mellitus, high
      fat diet feeding, and fasted mice were used to identify how decreased insulin
      signaling affects PFK-2 and cardiac metabolism. Primary adult cardiomyocytes were
      used to define the mechanisms that regulate PFK-2 degradation. Both type 1
      diabetes mellitus and a high-fat diet induced a significant decrease in cardiac
      PFK-2 protein content without affecting its transcript levels. Overnight fasting
      also induced a decrease in PFK-2, suggesting it is rapidly degraded in the
      absence of insulin signaling. An unbiased metabolomic study demonstrated that
      decreased PFK-2 in fasted animals is accompanied by an increase in glycolytic
      intermediates upstream of phosphofructokianse-1, whereas those downstream are
      diminished. Mechanistic studies using cardiomyocytes showed that, in the absence
      of insulin signaling, PFK-2 is rapidly degraded via both proteasomal- and
      chaperone-mediated autophagy. CONCLUSIONS: The loss of PFK-2 content as a result
      of reduced insulin signaling impairs the capacity to dynamically regulate
      glycolysis and elevates the levels of early glycolytic intermediates. Although
      this may be beneficial in the fasted state to conserve systemic glucose, it
      represents a pathological impairment in diabetes mellitus.

PMID- 29203583
TI  - How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation
      Analysis of the EMPA-REG OUTCOME Trial.
AB  - OBJECTIVE: In the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in
      Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial involving 7,020
      patients with type 2 diabetes and established cardiovascular (CV) disease,
      empagliflozin given in addition to standard of care reduced the risk of CV death
      by 38% versus placebo (hazard ratio [HR] 0.62 [95% CI 0.49, 0.77]). This
      exploratory mediation analysis assesses the extent to which treatment group
      differences in covariates during the trial contributed to CV death risk reduction
      with empagliflozin. RESEARCH DESIGN AND METHODS: Effects of potential mediators,
      identified post hoc, on the HR for CV death with empagliflozin versus placebo
      were analyzed by Cox regression models, with treatment group adjusted for the
      baseline value of the variable and its change from baseline or updated mean
      (i.e., considering all prior values), each as a time-dependent covariate. HRs
      were compared with a model without adjustment for covariates. Multivariable
      analyses also were performed. RESULTS: Changes in hematocrit and hemoglobin
      mediated 51.8% and 48.9%, respectively, of the effect of empagliflozin versus
      placebo on the risk of CV death on the basis of changes from baseline, with
      similar results in analyses on the basis of updated means. Smaller mediation
      effects (maximum 29.3%) were observed for uric acid, fasting plasma glucose, and
      HbA1c. In multivariable models, which incorporated effects of empagliflozin on
      hematocrit, fasting glucose, uric acid, and urine albumin:creatinine ratio, the
      combined changes from baseline provided 85.2% mediation, whereas updated mean
      analyses provided 94.6% mediation of the effect of empagliflozin on CV death.
      CONCLUSIONS: In this exploratory analysis from the EMPA-REG OUTCOME trial,
      changes in markers of plasma volume were the most important mediators of the
      reduction in risk of CV death with empagliflozin versus placebo.

PMID- 29203585
TI  - Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and
      Waldenstrom macroglobulinemia.
AB  - Novel therapies are needed for patients with relapsed or refractory multiple
      myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological
      malignancies to assess the safety, efficacy, and recommended phase 2 dose (RP2D)
      of oral selinexor, a selective inhibitor of the nuclear export protein XPO1. In
      the dose-escalation phase, 25 patients with heavily pretreated MM (22) or
      Waldenstrom macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8
      or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM
      received selinexor at 45 or 60 mg/m2 with 20 mg dexamethasone, twice weekly in 28
      day cycles, or selinexor (40 or 60 mg flat dose) without corticosteroids in 21
      day cycles. The most common nonhematologic adverse events (AEs) were nausea
      (75%), fatigue (70%), anorexia (64%), vomiting (43%), weight loss (32%), and
      diarrhea (32%), which were primarily grade 1 or 2. The most common grade 3 or 4
      AEs were hematologic, particularly thrombocytopenia (45%). Single-agent selinexor
      showed modest efficacy with an objective response rate (ORR) of 4% and clinical
      benefit rate of 21%. In contrast, the addition of dexamethasone increased the ORR
      with all responses of >=partial response occurring in the 45 mg/m2 selinexor plus
      20 mg dexamethasone twice weekly cohort (ORR = 50%). Furthermore, 46% of all
      patients showed a reduction in MM markers from baseline. Based on these findings,
      we conclude that selinexor in combination with dexamethasone is active in heavily
      pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone
      given twice weekly. This trial was registered at clinicaltrials.gov as
      #NCT01607892.

PMID- 29203586
TI  - COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8
      and CCL3 to recruit leukocytes via FPR2.
AB  - A natural leukocyte chemoattractant was isolated from bovine serum by an
      established four-step purification procedure. Based on its relative molecular
      mass of 7287 and NH2-terminal sequence, the protein was identified as a carboxy
      terminal peptide of the acute phase protein serum amyloid A (SAA) 1. This SAA1(46
      112) fragment and its human equivalent SAA1(47-104) were chemically synthesized.
      Unlike intact SAA1alpha, these SAA fragments failed to directly chemoattract
      neutrophils and monocytes, to induce chemokines and to stimulate downstream ERK
      signaling in monocytes. However, the SAA fragments potently synergized with CCL3
      to induce monocyte migration and with CXCL8 to stimulate neutrophil shape change
      and chemotaxis. Unlike intact SAA1alpha, SAA1(46-112) did not induce CXCL6 ex
      vivo, but provoked a cooperative intraperitoneal neutrophil recruitment in mice
      when co-injected with CXCL6 into the peritoneal cavity. Moreover, SAA1(47-104)
      desensitized the synergy between intact SAA1alpha and CXCL8 in neutrophil
      chemotaxis, suggesting that this peptide binds formyl peptide receptor (FPR) 2.
      This was evidenced by a complete blockade of synergy between the COOH-terminal
      SAA1 fragments and CXCL8 or CCL3 in neutrophil and monocyte chemotaxis,
      respectively, by the FPR2 antagonist WRW4 Thus, SAA1 is degraded into fragments
      lacking chemokine-inducing capacity, whilst keeping synergy with cytokine-induced
      chemokines to sustain limited inflammation.

PMID- 29203584
TI  - Fc-independent immune thrombocytopenia via mechanomolecular signaling in
      platelets.
AB  - Immune thrombocytopenia (ITP) is a prevalent autoimmune disease characterized by
      autoantibody-induced platelet clearance. Some ITP patients are refractory to
      standard immunosuppressive treatments such as intravenous immunoglobulin (IVIg).
      These patients often have autoantibodies that target the ligand-binding domain
      (LBD) of glycoprotein Ibalpha (GPIbalpha), a major subunit of the platelet
      mechanoreceptor complex GPIb-IX. However, the molecular mechanism of this Fc
      independent platelet clearance is not clear. Here, we report that many anti-LBD
      monoclonal antibodies such as 6B4, but not AK2, activated GPIb-IX in a shear
      dependent manner and induced IVIg-resistant platelet clearance in mice. Single
      molecule optical tweezer measurements of antibodies pulling on full-length GPIb
      IX demonstrated that the unbinding force needed to dissociate 6B4 from the LBD
      far exceeds the force required to unfold the juxtamembrane mechanosensory domain
      (MSD) in GPIbalpha, unlike the AK2-LBD unbinding force. Binding of 6B4, not AK2,
      induced shear-dependent unfolding of the MSD on the platelet, as evidenced by
      increased exposure of a linear sequence therein. Imaging flow cytometry and
      aggregometry measurements of platelets and LBD-coated platelet-mimetic beads
      revealed that 6B4 can sustain crosslinking of platelets under shear, whereas 6B4
      Fab and AK2 cannot. These results suggest a novel mechanism by which anti-LBD
      antibodies can exert a pulling force on GPIb-IX via platelet crosslinking,
      activating GPIb-IX by unfolding its MSD and inducing Fc-independent platelet
      clearance.

PMID- 29203587
TI  - NAMPT Is a Potent Oncogene in Colon Cancer Progression that Modulates Cancer Stem
      Cell Properties and Resistance to Therapy through Sirt1 and PARP.
AB  - Purpose: Colorectal cancer is the second most common cancer in women and the
      third most common in men worldwide. However, despite current progress, many
      patients with advanced and metastatic tumors still die from the malignancy.
      Refractory disease often relies on nicotinamide adenine dinucleotide (NAD)
      dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are
      required to maintain tissue homeostasis and metabolism. However, high levels of
      NAD confer therapy resistance to tumors.Experimental Design: Ectopic
      overexpression of nicotinamide phosphoribosil transferase (NAMPT) and shRNAs in
      colorectal cancer cell lines, tumorigenic and stemness properties and
      transcription measurement in culture and in vivo Transcriptional analysis in
      public databases. Therapeutic approaches.Results: NAMPT, the rate-limiting enzyme
      responsible for the highest source of physiologic NAD biosynthesis, increases
      tumorigenic properties and induces cancer stem cell-like properties through
      pathways that control stem cell signaling, thus enriching the cancer-initiating
      cell (CIC) population. Furthermore, NAMPT expression correlated with high levels
      of CIC-like cells in colon tumors directly extracted from patients, and
      transcription meta-analysis revealed that NAMPT is also a key factor that induces
      cancer stem pathways in colorectal cancer tumors. This effect is mediated by PARP
      and SIRT1. In addition, we report a novel NAMPT-driven signature that stratifies
      prognosis from high to low expression groups. The NAMPT signature contained SIRT1
      and PARP1 levels as well as other cancer stem cell-related genes. Finally, NAMPT
      inhibition increased the sensitivity to apoptosis in both NAMPT-expressing cells
      and tumorspheres.Conclusions: NAMPT represents a novel therapeutic target in
      colon cancer progression and relapse, particularly the CIC subset of human colon
      cancers. Clin Cancer Res; 24(5); 1202-15. (c)2017 AACR.

PMID- 29203588
TI  - Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel
      Immunotherapy Target in Human Non-Small Cell Lung Cancer.
AB  - Purpose: Determine the localized expression pattern and clinical significance of
      VISTA/PD-1H in human non-small cell lung cancer (NSCLC).Experimental Design:
      Using multiplex quantitative immunofluorescence (QIF), we performed localized
      measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3
      independent cohorts represented in tissue microarray format. The targets were
      selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T cells, CD4+ T
      helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes and CD68+ tumor
      associated macrophages. We determined the association between the targets,
      clinicopathological/molecular variables and survival. Genomic analyses of lung
      cancer cases from TCGA were also performed.Results: VISTA protein was detected in
      99% of NSCLCs with a predominant membranous/cytoplasmic staining pattern.
      Expression in tumor and stromal cells was seen in 21% and 98% of cases,
      respectively. The levels of VISTA were positively associated with PD-L1, PD-1,
      CD8+ T cells and CD68+ macrophages. VISTA expression was higher in T-lymphocytes
      than in macrophages; and in cytotoxic T cells than in T-helper cells. Elevated
      VISTA was associated with absence of EGFR mutations and lower mutational burden
      in lung adenocarcinomas. Presence of VISTA in tumor compartment predicted longer
      5-year survival.Conclusions: VISTA is frequently expressed in human NSCLC and
      shows association with increased tumor-infiltrating lymphocytes, PD-1 axis
      markers, specific genomic alterations and outcome. These results support the
      immunomodulatory role of VISTA in human NSCLC and suggests its potential as
      therapeutic target. Clin Cancer Res; 24(7); 1562-73. (c)2017 AACR.

PMID- 29203589
TI  - Lymph Node Metastases in Colon Cancer Are Polyclonal.
AB  - Purpose: Recent studies have highlighted the existence of subclones in tumors.
      Lymph nodes are generally the first location of metastasis for most solid
      epithelial tumors, including colorectal cancer. We sought to understand the
      genetic origin of lymph node metastasis in colorectal cancer by evaluating the
      relationship between colorectal cancer subclones present in primary tumors and
      lymph nodes.Experimental Design: A total of 33 samples from seven colorectal
      cancers, including two or three spatially disparate regions from each primary
      tumor and one to four matched lymph nodes for each tumor, underwent next
      generation whole-exome DNA sequencing, Affymetrix OncoScan SNP arrays, and
      targeted deep confirmatory sequencing. We performed mapping between SNPs and copy
      number events from the primary tumor and matched lymph node samples, allowing us
      to profile heterogeneity and the mutational origin of lymph node metastases. The
      computational method PyClone was used to define subclones within each tumor. The
      method Clonality Inference in Tumors Using Phylogeny (CITUP) was subsequently
      used to infer phylogenetic relationships among subclones.Results: We found that
      there was substantial heterogeneity in mutations and copy number changes among
      all samples from any given patient. For each patient, the primary tumor regions
      and matched lymph node metastases were each polyclonal, and the clonal
      populations differed from one lymph node to another. In some patients, the cancer
      cell populations in a given lymph node originated from multiple distinct regions
      of a tumor.Conclusions: Our data support a model of lymph node metastatic spread
      in colorectal cancer whereby metastases originate from multiple waves of seeding
      from the primary tumor over time. Clin Cancer Res; 24(9); 2214-24. (c)2017
      AACRSee related commentary by Gerlinger, p. 2032.

PMID- 29203590
TI  - A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15
      (rhIL15) in Adults with Advanced Solid Tumors.
AB  - Purpose: Preclinical data established IL15 as a homeostatic factor and powerful
      stimulator of NK and CD8+ T-cell function, the basis for clinical
      testing.Experimental Design: A first-in-human outpatient phase I dose escalation
      trial of subcutaneous (SC) rhIL15 was conducted in refractory solid tumor cancer
      patients. Therapy consisted of daily (Monday-Friday) subcutaneous injections of
      rhIL15 for two consecutive weeks (10 total doses/cycle). Clinical response was
      assessed by RECIST. Pharmacokinetics of rhIL15 and immune biomarkers were
      evaluated.Results: Nineteen patients were treated with rhIL15 at dose levels of
      0.25, 0.5, 1, 2, and 3 mcg/kg/day. Fourteen patients completed >= 2 cycles of
      therapy that was well tolerated. One serious adverse event (SAE), grade 2
      pancreatitis, required overnight hospitalization. Enrollment was halted after a
      patient receiving 3 mcg/kg/day developed a dose-limiting SAE of grade 3 cardiac
      chest pain associated with hypotension and increased troponin. No objective
      responses were observed; however, several patients had disease stabilization
      including a renal cell carcinoma patient who continued protocol treatment for 2
      years. The treatment induced profound expansion of circulating NK cells,
      especially among the CD56bright subset. A proportional but less dramatic increase
      was found among circulating CD8+ T cells with maximal 3-fold expansion for the 2
      and 3 mcg/kg patients.Conclusions: SC rhIL15 treatment was well tolerated,
      producing substantial increases in circulating NK and CD8+ T cells. This protocol
      establishes a safe outpatient SC rhIL15 regimen of 2 mcg/kg/day dosing amenable
      to self-injection and with potential as a combination immunotherapeutic agent.
      Clin Cancer Res; 24(7); 1525-35. (c)2017 AACR.

PMID- 29203591
TI  - Redundant let-7a suppresses the immunomodulatory properties of BMSCs by
      inhibiting the Fas/FasL system in osteoporosis.
AB  - Bone marrow-derived mesenchymal stem cell (BMSC) cytotherapy has emerged as a
      promising treatment strategy for refractory immune diseases; however, the
      influence of the pathologic conditions of donors on the immunomodulatory
      properties of BMSCs is still poorly understand. Here, we found that BMSCs that
      were derived from donors with osteoporosis were ineffective as cytotherapy for
      patients with experimental colitis and graft- vs.-host disease (GVHD). In vivo
      and in vitro assays revealed that the capacity of osteoporotic BMSCs to induce T
      cell apoptosis declined as a result of decreased Fas and FasL protein. Additional
      analysis revealed that let-7a, a microRNA induced by TNF-alpha in osteoporosis,
      inhibited the expression of the Fas/FasL system via post-transcriptional
      regulation. By knocking down let-7a expression, we successfully recovered the
      immunosuppressive capacity of osteoporotic BMSCs and improved their therapy for
      experimental colitis and GVHD. Taken together, our study demonstrates that the
      immunomodulatory properties of BMSCs are suppressed in osteoporosis and
      illustrates the molecular mechanism that underlies this suppression. These
      findings might have important implications for the development of targeted
      strategies to improve BMSC cytotherapy.-Liao, L., Yu, Y., Shao, B., Su, X., Wang,
      H., Kuang, H., Jing, H., Shuai, Y., Yang, D., Jin, Y. Redundant let-7a suppresses
      the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in
      osteoporosis.

PMID- 29203593
TI  - Loss of p53 compensates osteopenia in murine Mysm1 deficiency.
AB  - Histone modifications critically contribute to the epigenetic orchestration of
      bone homeostasis-in part, by modifying the access of transcription factors to
      specific genes involved in the osteogenic differentiation process of bone marrow
      mesenchymal stem cells (MSCs) and osteoblasts. Based on our previous finding that
      histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53 axis in
      hematopoiesis and tissue development, we analyzed the molecular basis of the
      skeletal phenotype of Mysm1-deficient mice and dissected the underlying p53
      dependent and -independent mechanisms. Visible morphologic, skeletal deformations
      of young Mysm1-deficient mice-including a kinked and truncated tail and shortened
      long bones-were associated with osteopenia of long bones. On the cellular level,
      Mysm1-deficient primary osteoblasts displayed reduced potential to differentiate
      into mature osteoblasts, as indicated by decreased expression of osteogenic
      markers. Reduced osteogenic differentiation capacity of Mysm1-deficient
      osteoblasts was accompanied by an impaired induction of osteogenic transcription
      factor Runx2. Osteogenic differentiation of Mysm1-/- MSCs, however, was not
      compromised in vitro. In line with defective hematopoietic development of Mysm1
      deficient mice, Mysm1-/- osteoclasts had reduced resorption activity and were
      more prone to apoptosis in TUNEL assays. Skeletal alterations and osteopenia of
      Mysm1-deficient mice were phenotypically completely rescued by simultaneous
      ablation of p53 in p53-/-Mysm1-/- double-deficient mice-although p53 deficiency
      did not restore Runx2 expression in Mysm1-/- osteoblasts on the molecular level
      but, instead, enhanced proliferation and osteogenic differentiation of MSCs. In
      summary, our results demonstrate novel roles for Mysm1 in osteoblast
      differentiation and osteoclast formation, resulting in osteopenia in Mysm1
      deficient mice that could be abrogated by the loss of p53 from increased
      osteogenic differentiation of Mysm1-/-p53-/- MSCs.-Haffner-Luntzer, M., Kovtun,
      A., Fischer, V., Prystaz, K., Hainzl, A., Kroeger, C. M., Krikki, I., Brinker, T.
      J., Ignatius, A., Gatzka, M. Loss of p53 compensates osteopenia in murine Mysm1
      deficiency.

PMID- 29203592
TI  - Correction of GSK3beta at young age prevents muscle pathology in mice with
      myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by
      expanded CUG repeats, which misregulate RNA metabolism through several RNA
      binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1
      (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and
      alter CUGBP1 activity via a glycogen synthase kinase 3beta (GSK3beta)-cyclin D3
      cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3beta
      corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA,
      containing long repeats ( HSALR) model]. Here, we show that the inhibition of
      GSK3beta in young HSALR mice prevents development of DM1 muscle pathology.
      Skeletal muscle in 1-yr-old HSALR mice, treated at 1.5 mo for 6 wk with the
      inhibitors of GSK3, exhibits high fiber density, corrected atrophy, normal fiber
      size, with reduced central nuclei and normalized grip strength. Because CUG
      GSK3beta-cyclin D3-CDK4 converts the active form of CUGBP1 into a form of
      translational repressor, we examined the contribution of CUGBP1 in myogenesis
      using Celf1 knockout mice. We found that a loss of CUGBP1 disrupts myogenesis,
      affecting genes that regulate differentiation and the extracellular matrix.
      Proteins of those pathways are also misregulated in young HSALR mice and in
      muscle biopsies of patients with congenital DM1. These findings suggest that the
      correction of GSK3beta-CUGBP1 pathway in young HSALR mice might have a positive
      effect on the myogenesis over time.-Wei, C., Stock, L., Valanejad, L., Zalewski,
      Z. A., Karns, R., Puymirat, J., Nelson, D., Witte, D., Woodgett, J., Timchenko,
      N. A., Timchenko, L. Correction of GSK3beta at young age prevents muscle
      pathology in mice with myotonic dystrophy type 1.

PMID- 29203595
TI  - Increased Mortality and Health Risk Behaviors of Midlife White North Carolinians:
      A Marked Contrast to Nonwhites.
AB  - BACKGROUND Death rates for white, middle-aged Americans are increasing after
      decades of steady decline. In this paper, mortality and health behavior trends
      are examined for midlife North Carolinians.METHODS Mortality rates were
      calculated for midlife whites from 2000 to 2013 for the state as a whole and in
      counties grouped by level of economic distress. Trend lines were used to estimate
      future death rates, and comparisons were made to rates for nonwhites. Current and
      past health risk behaviors were also analyzed.RESULTS The all-cause mortality
      rate for midlife whites in North Carolina was higher than the 2000 base in 11 of
      13 years; white midlife mortality increased by 5.9%. In contrast, nonwhite
      mortality decreased by 30.6%. By 2020, midlife mortality for whites is predicted
      to increase by 9.1%; for nonwhites, there is a predicted decrease of 47.2%.
      Midlife white mortality increased most in economically distressed counties. Major
      contributors were suicide and liver disease. Risk factors that increased were
      drinking, obesity, and lack of health insurance.LIMITATIONS Mortality and risk
      factor data could not be analayzed by ethnicity. Deaths due to drug and alcohol
      poisoning were not included.CONCLUSIONS The statewide mortality rate for midlife
      whites in North Carolina is increasing and is in marked contrast to the
      decreasing rate for nonwhites. The racial disparity in this metric is likely to
      be eliminated by 2020, perhaps even reversed. Midlife white mortality increased
      most dramatically in the state's poorest counties. Policymakers should consider
      links between economic issues and health behaviors involved in midlife mortality
      and why they may affect whites and nonwhites differently.

PMID- 29203596
TI  - Policy Forum. More than Just a Pretty Smile.

PMID- 29203594
TI  - Responding to a Community's Concern: A Comparison of Breast Cancer
      Characteristics and Initial Treatment in Three Selected North Carolina Counties.
AB  - BACKGROUND A 2007 national report identified North Carolina's Edgecombe County as
      having among the highest breast cancer incidence and mortality rates nationally,
      motivating the initiation of a task force and other local efforts to address the
      problem. The goal of this study is to examine county breast cancer
      characteristics before and after the report, including whether geographic
      variation may mask racial disparities in this majority African American
      community.METHOD With guidance from community partners, breast cancer cases from
      2000 to 2012 in Edgecombe, Nash, and Orange Counties (N = 2,641) were obtained
      from the North Carolina Central Cancer Registry. Bivariate and trend analyses of
      tumor and treatment characteristics were examined by county and race.RESULTS
      Women in Edgecombe and Nash Counties were diagnosed with more advanced stage,
      higher grade tumors. African Americans in Edgecombe and Nash Counties were
      diagnosed with advanced disease more often than African Americans in Orange
      County. Average time-to-treatment was well within guideline recommendations.
      Incidence and mortality rates appear to have declined, with variation in measures
      of racial differences over time.LIMITATIONS Changes in coding standards across
      the observation period required reliance on coarse measures that may partially
      mute useful findings.CONCLUSIONS Racial disparities remain a concern in North
      Carolina; however, they appear to be less profound than in the 2007 national
      report. The portentous statistics in the report represent an all-time high, after
      which some, but not all, measures reflect positive change amidst ongoing local
      efforts to improve breast cancer knowledge and care.

PMID- 29203597
TI  - Perspectives on Innovations in Oral Health Care.
AB  - A downward trend in dental caries in permanent teeth of children that began in
      the 1970s has leveled out at historic lows. Severe periodontal disease affects a
      small percentage of people, and tooth loss has plummeted so that complete tooth
      loss, once a common occurrence, now is almost non-existent in upper socioeconomic
      groups. But not all people have benefited equally from these positive trends.
      Dental problems continue to affect the disadvantaged in society at unacceptable
      rates, and their disease burden is likely to increase because of trends in social
      determinants of oral diseases.Personal dental care alone usually is unable to
      provide a sufficient buffer against these risks to maintain adequate oral health.
      Extensive disease in young children too often requires treatment in the hospital
      with a high chance of relapse. A national health goal is to "achieve health
      equity, eliminate disparities, and improve the health of all groups." Achieving
      this goal in oral health requires that things be done differently.This issue of
      the North Carolina Medical Journal highlights several approaches being tried here
      in North Carolina and elsewhere to address oral health problems. Initiatives fall
      into 4 categories: advocacy, workforce policies, integration of oral health and
      primary care, and the medical management of caries.

PMID- 29203598
TI  - Community Dental Health Coordinators: Cultural "Connectors" for Oral Health.
AB  - The American Dental Association's Community Dental Health Coordinator program was
      designed to teach community health worker skills to dental auxiliaries. Case
      management, a valued skill utilized by medical providers, is largely unknown in
      the dental profession. When case management is incorporated into a dental
      professional's practice, prevention becomes amplified, leading to decreased costs
      and increased access.

PMID- 29203599
TI  - A Commentary on Pediatric Oral Health in North Carolina.
AB  - Pediatric oral health care in North Carolina has taken a unique path to its
      current form and will require similar innovation to counter headwinds to its
      continued success. This commentary describes that path and attempts to set a
      vision and strategy for the future that leverages Community Care of North
      Carolina's infrastructure and continues to promote the expansion of clinical
      guidelines for pediatric preventive oral health care for vulnerable populations.

PMID- 29203600
TI  - Highlights of North Carolina Oral Health Section's 2015-2016 Kindergarten
      Assessment Data.

PMID- 29203601
TI  - Why an Equity Lens is Essential for Achieving Oral Health for All: Exploring
      Collaboration as a Path to Systems Change.
AB  - To overcome persistent disparities in oral health access and status, it is vital
      we adopt a paradigm shift from addressing symptoms to also addressing root
      causes. This article delineates why an equity lens and a collaborative systems
      change approach are essential elements.

PMID- 29203602
TI  - A New Way to Measure Geographic Access to Dentists in North Carolina.

PMID- 29203603
TI  - Silver Diamine Fluoride: Changing the Caries Management Paradigm and Potential
      Societal Impact.
AB  - Silver diamine fluoride is a topically-applied agent for managing dental caries.
      It stops caries lesion progression, turning them black and hard in a high
      percentage of cases. Populations including pediatric, geriatric, special health
      care needs, and those with limited access to oral health care can all benefit
      from silver diamine fluoride. This commentary addresses some of the many
      questions that have arisen with the availability of SDF and marked gaps in our
      knowledge.

PMID- 29203604
TI  - The Journey to Improving Access to Dental Services for Individuals in Assisted
      Living Facilities Across North Carolina.
AB  - Access to oral health services for individuals within assisted living facilities
      had never been investigated on a statewide level. This commentary provides an
      overview of this issue and discusses a recent statewide surveillance survey that
      can help improve outcomes and access to dental services for residents of assisted
      living facilities.

PMID- 29203606
TI  - Integrating Oral Health and Primary Care in the Changing Health Care Landscape.
AB  - The bi-directional relationship among oral health and other systemic diseases and
      conditions provides a strong rationale for integration of oral health and primary
      care practice. Patient care services may be coordinated across different times,
      places, and professional disciplines to provide a team approach to care for
      overall health.

PMID- 29203605
TI  - Integrating Oral Health Care Services Within Medicare.
AB  - The idea of a Medicare oral health benefit is attracting attention. Models for
      care that focus on screening, prevention, and early intervention have been
      developed. East Carolina University's Community Service Learning Centers are well
      positioned to work with community partners to extend care to older adults in
      rural areas.

PMID- 29203607
TI  - Connecting Oral and Physical Health via the Health Information Exchange.
AB  - In 2015 North Carolina passed the Health Information Exchange Act, which mandates
      that all providers who receive state funds for the provision of health care
      services must connect and submit patient clinical and demographic data to the
      state-designated health information exchange by certain dates in 2018 and 2019.
      This article explains the statute and the benefits of health information exchange
      to support better oral health care.

PMID- 29203608
TI  - The Critical Role Youth Play in Addressing Oral Health Inequities.

PMID- 29203609
TI  - Running the Numbers: Oral Health Trends from the North Carolina Behavioral Risk
      Factor Surveillance System, 2012-2016.

PMID- 29203610
TI  - Philanthropy Profile: Working Together for Oral Health in the Carolinas.

PMID- 29203611
TI  - NCIOM Issue Brief: Metrics to Drive Improvements in Health October 2017.

PMID- 29203612
TI  - The Danger of Carbon Monoxide Poisoning Associated with Hookah Use: An Emergency
      Physician's Perspective.

PMID- 29203613
TI  - Nfe2l1-silenced insulinoma cells acquire aggressiveness and chemoresistance.
AB  - The transcription factor nuclear factor erythroid 2-like 1 (NFE2L1 or NRF1) is
      involved in various critical cell processes such as maintenance of ubiquitin
      proteasome system and regulation of the cellular antioxidant response. We
      previously determined that pancreatic beta-cell-specific Nfe2l1-knockout mice had
      hyperinsulinemia and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma
      beta-cells induced elevated basal insulin release and altered glucose metabolism.
      Hypoglycemia is a major issue with aggressive insulinomas, although a role of
      NFE2L1 in this pathology is not defined. In the present work, we studied the
      tumorigenicity of Nfe2l1-deficient insulinoma MIN6 cells (Nfe2l1-KD) and
      sensitivity to chemotherapy. Nfe2l1-KD cells grew faster and were more aggressive
      than Scramble cells in vitro In a mouse allograft transplantation model,
      insulinomas arising from Nfe2l1-KD cells were more aggressive and chemoresistant.
      The conclusion was amplified using streptozotocin (STZ) administration in an
      allograft transplantation model in diabetic Akita background mice. Furthermore,
      Nfe2l1-KD cells were resistant to damage by the chemotherapeutic drugs STZ and 5
      fluorouracil, which was linked to binding of hexokinase 1 with mitochondria,
      enhanced mitochondrial membrane potential and closed mitochondrial potential
      transition pore. Overall, both in vitro and in vivo data from Nfe2l1-KD
      insulinoma cells provided evidence of a previously un-appreciated action of
      NFE2L1 in suppression of tumorigenesis. Nfe2l1 silencing desensitizes insulinoma
      cells and derived tumors to chemotherapeutic-induced damage, likely via metabolic
      reprograming. These data indicate that NFE2L1 could potentially play an important
      role in the carcinogenic process and impact chemosensitivity, at least within a
      subset of pancreatic endocrine tumors.

PMID- 29203614
TI  - Copy number profiling of oncogenes in ductal carcinoma in situ of the male
      breast.
AB  - Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis
      is challenging because of the rarity of this disease. We investigated copy number
      status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS)
      and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males
      using multiplex ligation-dependent probe amplification (MLPA). Results were
      compared to female BC and correlated with survival. Overall, copy number ratio
      and aberration frequency including all 22 genes showed no significant difference
      between the 3 groups. Individual unpaired analysis revealed a significantly
      higher MTDH copy number ratio in IC compared to DCIS-AIC and pure DCIS (P = 0.009
      and P = 0.038, respectively). ADAM9 showed a significantly lower copy number
      aberration frequency in male BC, compared to female BC (P = 0.020). In DCIS-AIC,
      MTDH, CPD, CDC6 and TOP2A showed a lower frequency of copy number increase in
      males compared to females (P < 0.001 for all 4 genes). In IC, CPD gain and CCNE1
      gain were independent predictors of poor overall survival. In conclusion, male
      DCIS and IC showed a similar copy number profile for 21 out of 22 interrogated BC
      related genes, illustrating their clonal relation and the genetically advanced
      state of male DCIS. MTDH showed a higher copy number ratio in IC compared to
      adjacent and pure DCIS and may therefore play a role in male breast
      carcinogenesis. Differences were detected between male and female DCIS for 4
      genes pointing to differences in breast carcinogenesis between the sexes.

PMID- 29203615
TI  - Charting age-associated cognitive decline.

PMID- 29203616
TI  - Validation and diagnostic accuracy of predictive curves for age-associated
      longitudinal cognitive decline in older adults.
AB  - BACKGROUND: The Mini-Mental State Examination continues to be used frequently to
      screen for cognitive impairment in older adults, but it remains unclear how to
      interpret changes in its score over time to distinguish age-associated cognitive
      decline from an early degenerative process. We aimed to generate cognitive charts
      for use in clinical practice for longitudinal evaluation of age-associated
      cognitive decline. METHODS: We used data from the Canadian Study of Health and
      Aging from 7569 participants aged 65 years or older who completed a Mini-Mental
      State Examination at baseline, and at 5 and 10 years later to develop a linear
      regression model for the Mini-Mental State Examination score as a function of age
      and education. Based on this model, we generated cognitive charts designed to
      optimize accuracy for distinguishing participants with dementia from healthy
      controls. We validated our model using a separate data set of 6501 participants
      from the National Alzheimer's Coordinating Center's Uniform Data Set. RESULTS:
      For baseline measurement, the cognitive charts had a sensitivity of 80% (95%
      confidence interval [CI] 75% to 84%) and a specificity of 89% (95% CI 88% to 90%)
      for distinguishing healthy controls from participants with dementia. Similar
      sensitivities and specificities were observed for a decline over time greater
      than 1 percentile zone from the first measurement. Results in the validation
      sample were comparable, albeit with lower sensitivities. Negative predictive
      value was 99%. INTERPRETATION: Our innovative model, which factors in age and
      education, showed validity and diagnostic accuracy for determining whether older
      patients show abnormal performance on serial Mini-Mental State Examination
      measurements. Similar to growth curves used in pediatrics, cognitive charts allow
      longitudinal cognitive evaluation and enable prompt initiation of investigation
      and treatment when appropriate.

PMID- 29203619
TI  - Majocchi granuloma in a 58-year-old man with treatment-resistant annular scaling
      plaque.

PMID- 29203618
TI  - Congenitally transmitted Chagas disease in Canada: a family cluster.

PMID- 29203617
TI  - Diagnosis and treatment of obstructive sleep apnea in adults.

PMID- 29203620
TI  - Could changes in pharmacotherapy peripregnancy contribute to the shift in means
      of suicide?

PMID- 29203621
TI  - Mental health care and suicide in pregnancy and postpartum.

PMID- 29203622
TI  - Quebec medical schools slow to adopt pass/fail system.

PMID- 29203623
TI  - Postsecondary campuses responding to record anxiety and depression levels.

PMID- 29203624
TI  - Quebec grants health minister power to impose duties on doctors.

PMID- 29203626
TI  - Exaggerated Sympathetic Neurovascular Transduction as a Mechanism of Neurogenic
      Hypertension: It Is Not All About Activity.

PMID- 29203625
TI  - Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe
      and Early-Onset Preeclampsia.
AB  - Preeclampsia is a vascular pregnancy disorder that often involves impaired
      placental development. HO-1 (heme oxygenase 1, encoded by HMOX1) is a stress
      response enzyme crucial for endothelial and placental function. Long version of
      the guanine-thymine (GTn) microsatellite in the HMOX1 promoter decreases HO-1
      expression, and the long maternal repeat is associated with late-onset
      preeclampsia. Our aim was to study whether the length of fetal repeat is
      associated with mother's preeclampsia, whether the length of fetal and maternal
      repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1
      levels are altered in preeclampsia. We genotyped the repeat in the cord blood of
      609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in
      36 placental samples, and in the first (222 cases/243 controls) and third (176
      cases/53 controls) pregnancy trimester serum samples using enzyme-linked
      immunosorbent assay. The long fetal GTn repeat was associated with preeclampsia
      and its severe and early-onset subtypes. Interaction analysis suggested the
      maternal and fetal effects to be independent. Placental or serum HO-1 levels were
      not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia.
      Carriers of the long fetal and maternal repeats had lower placental and serum HO
      1 levels, respectively, providing functional evidence for the association. We
      conclude that the long fetal GTn repeat may increase mother's risk for especially
      severe and early-onset preeclampsia. The fetal and maternal risk alleles likely
      predispose to different disease subtypes.

PMID- 29203627
TI  - Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.
AB  - Obese patients have vascular dysfunction related to impaired insulin-stimulated
      vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to
      the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting
      enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic
      benefits in experimental models through stimulation of the Mas receptor. We,
      therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and
      endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial
      infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in
      unstimulated forearm flow (P=0.03), an effect that was not affected by the Mas
      receptor antagonist A779 (10 nmol/min; P>0.05). In the absence of
      hyperinsulinemia, however, forearm flow responses to graded doses of
      acetylcholine and sodium nitroprusside were not different during Ang-(1-7)
      administration compared with saline (both P>0.05). During infusion of regular
      insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator
      response to acetylcholine was significantly enhanced by Ang-(1-7) (P=0.04 versus
      saline), whereas endothelium-independent response to sodium nitroprusside was not
      modified (P=0.91). Finally, Ang-(1-7) decreased the vasodilator response to
      endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6+/-1%
      versus 93+/-17%; P<0.001); nitric oxide inhibition by l-N-monomethylarginine (4
      umol/min) during concurrent endothelin A antagonism resulted in similar
      vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) (P=0.69). Our
      findings indicate that in obese patients Ang-(1-7) has favorable effects not only
      to improve insulin-stimulated endothelium-dependent vasodilation but also to
      blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support
      for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human
      obesity.

PMID- 29203628
TI  - Predicting Out-of-Office Blood Pressure in the Clinic for the Diagnosis of
      Hypertension in Primary Care: An Economic Evaluation.
AB  - Clinical guidelines in the United States and United Kingdom recommend that
      individuals with suspected hypertension should have ambulatory blood pressure
      (BP) monitoring to confirm the diagnosis. This approach reduces misdiagnosis
      because of white coat hypertension but will not identify people with masked
      hypertension who may benefit from treatment. The Predicting Out-of-Office Blood
      Pressure (PROOF-BP) algorithm predicts masked and white coat hypertension based
      on patient characteristics and clinic BP, improving the accuracy of diagnosis
      while limiting subsequent ambulatory BP monitoring. This study assessed the cost
      effectiveness of using this tool in diagnosing hypertension in primary care. A
      Markov cost-utility cohort model was developed to compare diagnostic strategies:
      the PROOF-BP approach, including those with clinic BP >=130/80 mm Hg who receive
      ambulatory BP monitoring as guided by the algorithm, compared with current
      standard diagnostic strategies including those with clinic BP >=140/90 mm Hg
      combined with further monitoring (ambulatory BP monitoring as reference, clinic,
      and home monitoring also assessed). The model adopted a lifetime horizon with a 3
      month time cycle, taking a UK Health Service/Personal Social Services
      perspective. The PROOF-BP algorithm was cost-effective in screening all patients
      with clinic BP >=130/80 mm Hg compared with current strategies that only screen
      those with clinic BP >=140/90 mm Hg, provided healthcare providers were willing
      to pay up to L20 000 ($26 000)/quality-adjusted life year gained. Deterministic
      and probabilistic sensitivity analyses supported the base-case findings. The
      PROOF-BP algorithm seems to be cost-effective compared with the conventional BP
      diagnostic options in primary care. Its use in clinical practice is likely to
      lead to reduced cardiovascular disease, death, and disability.

PMID- 29203630
TI  - Angiotensin-(1-7) and Vascular Function: The Clinical Context.

PMID- 29203629
TI  - Exaggerated Vasoconstriction to Spontaneous Bursts of Muscle Sympathetic Nerve
      Activity in Healthy Young Black Men.
AB  - Blacks have the highest prevalence of hypertension, putting them at greater risk
      of cardiovascular disease and death. Previous studies have reported that,
      relative to whites, healthy black men have augmented pressor responses to
      sympathoexcitatory stressors. Although important, these studies do not inform
      about the resting state and the influence of spontaneous changes in resting
      muscle sympathetic nerve activity (MSNA). Likewise, little is known about the
      transduction of MSNA into a vascular response at rest on a beat-to-beat basis.
      Accordingly, we tested the hypothesis that relative to whites, blacks would
      exhibit greater vasoconstriction and pressor responses following spontaneous
      bursts of MSNA. Mean arterial pressure, common femoral artery blood flow, and
      MSNA were continuously recorded during 20 minutes of supine rest in 35 young
      healthy men (17 blacks and 18 whites). Signal averaging was used to characterize
      changes in leg vascular conductance, total vascular conductance, and mean
      arterial pressure following spontaneous MSNA bursts. Blacks demonstrated
      significantly greater decreases in leg vascular conductance (blacks: -15.0+/
      1.0%; whites: -11.5+/-1.2%; P=0.042) and total vascular conductance (blacks: 
      8.6+/-0.9%; whites: -5.1+/-0.4%; P=0.001) following MSNA bursts, which resulted
      in greater mean arterial pressure increases (blacks: +5.2+/-0.6 mm Hg; whites:
      +3.9+/-0.3 mm Hg; P=0.04). These exaggerated responses in blacks compared with
      whites were present whether MSNA bursts occurred in isolation (singles) or in
      combination (multiples) and were graded with increases in burst height.
      Collectively, these findings suggest that healthy young black men exhibit
      augmented sympathetic vascular transduction at rest and provide novel insight
      into potential mechanism(s) by which this population may develop hypertension
      later in life.

PMID- 29203631
TI  - Hyperuricemia: Does It Matter for the Progression From Prehypertension to
      Hypertension?

PMID- 29203633
TI  - 'Twitterland': a brave new world?

PMID- 29203632
TI  - Uric Acid Is a Strong Risk Marker for Developing Hypertension From
      Prehypertension: A 5-Year Japanese Cohort Study.
AB  - Prehypertension frequently progresses to hypertension, a condition associated
      with high morbidity and mortality from cardiovascular diseases and stroke.
      However, the risk factors for developing hypertension from prehypertension remain
      poorly understood. We conducted a retrospective cohort study using the data from
      3584 prehypertensive Japanese adults (52.1+/-11.0 years, 2081 men) found to be
      prehypertensive in 2004 and reexamined in 2009. We calculated the cumulative
      incidences of hypertension over 5 years, examined risk factors, and calculated
      odds ratios (ORs) for developing hypertension after adjustments for age, sex,
      body mass index, smoking and drinking habits, baseline systolic and diastolic
      blood pressure, pulse rate, diabetes mellitus, dyslipidemia, chronic kidney
      disease, and serum uric acid levels. The additional analysis evaluated whether
      serum uric acid (hyperuricemia) constituted an independent risk factor for
      developing hypertension. The cumulative incidence of hypertension from
      prehypertension over 5 years was 25.3%. There were no significant differences
      between women and men (24.4% versus 26.0%; P=0.28). The cumulative incidence of
      hypertension in subjects with hyperuricemia (n=726) was significantly higher than
      those without hyperuricemia (n=2858; 30.7% versus 24.0%; P<0.001). After
      multivariable adjustments, the risk factors for developing hypertension from
      prehypertension were age (OR, 1.023; P<0.001), female sex (OR, 1.595; P<0.001),
      higher body mass index (OR, 1.051; P<0.001), higher baseline systolic (OR, 1.072;
      P<0.001) and diastolic blood pressure (OR, 1.085; P<0.001), and higher serum uric
      acid (OR, 1.149; P<0.001). Increased serum uric acid is a strong risk marker for
      developing hypertension from prehypertension. Further studies are needed to
      determine whether treatment of hyperuricemia in prehypertensive subjects could
      impede the onset of hypertension.

PMID- 29203635
TI  - Epitranscriptomics and Flowering: mRNA Methylation/Demethylation Regulates
      Flowering Time.

PMID- 29203634
TI  - Mediator Complex Subunits MED2, MED5, MED16, and MED23 Genetically Interact in
      the Regulation of Phenylpropanoid Biosynthesis.
AB  - The phenylpropanoid pathway is a major global carbon sink and is important for
      plant fitness and the engineering of bioenergy feedstocks. In Arabidopsis
      thaliana, disruption of two subunits of the transcriptional regulatory Mediator
      complex, MED5a and MED5b, results in an increase in phenylpropanoid accumulation.
      By contrast, the semidominant MED5b mutation reduced epidermal fluorescence4-3
      (ref4-3) results in dwarfism and constitutively repressed phenylpropanoid
      accumulation. Here, we report the results of a forward genetic screen for
      suppressors of ref4-3. We identified 13 independent lines that restore growth
      and/or phenylpropanoid accumulation in the ref4-3 background. Two of the
      suppressors restore growth without restoring soluble phenylpropanoid
      accumulation, indicating that the growth and metabolic phenotypes of the ref4-3
      mutant can be genetically disentangled. Whole-genome sequencing revealed that all
      but one of the suppressors carry mutations in MED5b or other Mediator subunits.
      RNA-seq analysis showed that the ref4-3 mutation causes widespread changes in
      gene expression, including the upregulation of negative regulators of the
      phenylpropanoid pathway, and that the suppressors reverse many of these changes.
      Together, our data highlight the interdependence of individual Mediator subunits
      and provide greater insight into the transcriptional regulation of
      phenylpropanoid biosynthesis by the Mediator complex.

PMID- 29203636
TI  - Identification of potential pathogenic genes associated with osteoporosis.
AB  - OBJECTIVES: Osteoporosis is a chronic disease. The aim of this study was to
      identify key genes in osteoporosis. METHODS: Microarray data sets GSE56815 and
      GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples,
      were obtained from the Gene Expression Omnibus database. Differentially expressed
      genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta
      MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment
      analyses were performed to identify biological functions. Furthermore, the
      transcriptional regulatory network was established between the top 20 DEGs and
      transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating
      characteristic (ROC) analysis was applied to investigate the diagnostic value of
      several DEGs. RESULTS: A total of 1320 DEGs were obtained, of which 855 were up
      regulated and 465 were down-regulated. These differentially expressed genes were
      enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes
      pathways, mainly associated with gene expression and osteoclast differentiation.
      In the transcriptional regulatory network, there were 6038 interactions pairs
      involving 88 transcriptional factors. In addition, the quantitative reverse
      transcriptase-polymerase chain reaction result validated the expression of
      several genes (VPS35, FCGR2A, TBCA, HIRA, TYROBP, and JUND). Finally, ROC
      analyses showed that VPS35, HIRA, PHF20 and NFKB2 had a significant diagnostic
      value for osteoporosis. CONCLUSION: Genes such as VPS35, FCGR2A, TBCA, HIRA,
      TYROBP, JUND, PHF20, NFKB2, RPL35A and BICD2 may be considered to be potential
      pathogenic genes of osteoporosis and may be useful for further study of the
      mechanisms underlying osteoporosis.Cite this article: B. Xia, Y. Li, J. Zhou, B.
      Tian, L. Feng. Identification of potential pathogenic genes associated with
      osteoporosis. Bone Joint Res 2017;6:640-648. DOI: 10.1302/2046-3758.612.BJR-2017
      0102.R1.

PMID- 29203637
TI  - Can zinc protect cells from the cytotoxic effects of cobalt ions and
      nanoparticles derived from metal-on-metal joint arthroplasties?
AB  - OBJECTIVES: Recently, high failure rates of metal-on-metal (MOM) hip implants
      have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt
      nanoparticles (CoNPs) and cobalt ions (Co2+) during wear of MOM hip implants, but
      the toxic mechanism is not clear. METHODS: To evaluate the protective effect of
      zinc ions (Zn2+), Balb/3T3 mouse fibroblast cells were pretreated with 50 MUM
      Zn2+ for four hours. The cells were then exposed to different concentrations of
      CoNPs and Co2+ for four hours, 24 hours and 48 hours. The cell viabilities,
      reactive oxygen species (ROS) levels, and inflammatory cytokines were measured.
      RESULTS: CoNPs and Co2+ can induce the increase of ROS and inflammatory
      cytokines, such as tumour necrosis factor alpha (TNF-alpha), interleukin-1beta
      (IL-1beta) and interleukin-6 (IL-6). However, Zn pretreatment can significantly
      prevent cytotoxicity induced by CoNPs and Co2+, decrease ROS production, and
      decrease levels of inflammatory cytokines in Balb/3T3 mouse fibroblast cells.
      CONCLUSION: These results suggest that Zn pretreatment can provide protection
      against inflammation and cytotoxicity induced by CoNPs and Co2+ in Balb/3T3
      cells.Cite this article: Y. Liu, H. Zhu, H. Hong, W. Wang, F. Liu. Can zinc
      protect cells from the cytotoxic effects of cobalt ions and nanoparticles derived
      from metal-on-metal joint arthroplasties? Bone Joint Res 2017;6:649-655. DOI:
      10.1302/2046-3758.612.BJR-2016-0137.R2.

PMID- 29203638
TI  - Cytokines in tendon disease: A Systematic Review.
AB  - OBJECTIVES: Emerging evidence indicates that tendon disease is an active process
      with inflammation that is critical to disease onset and progression. However, the
      key cytokines responsible for driving and sustaining inflammation have not been
      identified. METHODS: We performed a systematic review of the literature using
      MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017.
      Studies reporting the expression of interleukins (ILs), tumour necrosis factor
      alpha (TNF-alpha) and interferon gamma in diseased human tendon tissues, and
      animal models of tendon injury or exercise in comparison with healthy control
      tissues were included. RESULTS: IL-1beta, IL-6, IL-10, and TNF-alpha are the
      cytokines that have been most frequently investigated. In clinical samples of
      tendinopathy and tendon tears, the expression of TNF-alpha tended not to change
      but IL-6 increased in tears. Healthy human tendons showed increased IL-6
      expression after exercise; however, IL-10 remained unchanged. Animal tendon
      injury models showed that IL-1beta, IL-6, and TNF-alpha tend to increase from the
      early phase of tendon healing. In animal exercise studies, IL-1beta expression
      showed a tendency to increase at the early stage after exercise, but IL-10
      expression remained unchanged with exercise. CONCLUSIONS: This review highlights
      the roles of IL-1beta, IL-6, IL-10, and TNF-alpha in the development of tendon
      disease, during tendon healing, and in response to exercise. However, there is
      evidence accumulating that suggests that other cytokines are also contributing to
      tendon inflammatory processes. Further work with hypothesis-free methods is
      warranted in order to identify the key cytokines, with subsequent mechanistic and
      interaction studies to elucidate their roles in tendon disease development.Cite
      this article: W. Morita, S. G. Dakin, S. J. B. Snelling, A. J. Carr. Cytokines in
      tendon disease: A Systematic Review. Bone Joint Res 2017;6:656-664. DOI:
      10.1302/2046-3758.612.BJR-2017-0112.R1.

PMID- 29203639
TI  - A Knock-In Tristetraprolin (TTP) Zinc Finger Point Mutation in Mice: Comparison
      with Complete TTP Deficiency.
AB  - Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that can bind to AU
      rich element-containing mRNAs and promote their decay. TTP knockout mice develop
      a severe inflammatory syndrome, largely due to excess tumor necrosis factor
      (TNF), whose mRNA is a direct target of TTP binding and destabilization. TTP's
      RNA binding activity and its ability to promote mRNA decay are lost when one of
      the zinc-coordinating residues of either zinc finger is mutated. To address
      several long-standing questions about TTP activity in intact animals, we
      developed a knock-in mouse with a cysteine-to-arginine mutation within the first
      zinc finger. Homozygous knock-in mice developed a severe inflammatory syndrome
      that was essentially identical to that of complete TTP deficiency, suggesting
      that TTP's critical anti-inflammatory role in mammalian physiology is secondary
      to its ability to bind RNA. In addition, there was no evidence for a "dominant
      negative" effect of the mutant allele in heterozygotes, as suggested by previous
      experiments. Finally, mRNA decay experiments in mutant macrophages demonstrated
      that TTP can regulate the stability of its own mRNA, albeit to a minor extent.
      These studies suggest that RNA binding is an essential first step in the
      physiological activities of members of this protein family.

PMID- 29203640
TI  - Transforming Growth Factor beta-Induced Proliferative Arrest Mediated by TRIM26
      Dependent TAF7 Degradation and Its Antagonism by MYC.
AB  - Recognition of gene promoters by RNA polymerase II is mediated by general
      transcription factor IID (TFIID), which has been thought to be a static complex
      and to play a passive role in the regulation of gene expression under the
      instruction of gene-specific transcription factors. Here we show that
      transforming growth factor beta (TGF-beta) induced degradation of the TFIID
      subunit TAF7 in cultured mouse mammary epithelial cells and that this effect was
      required for proliferative arrest in response to TGF-beta stimulation. TGF-beta
      stimulated transcription of the gene for the ubiquitin ligase TRIM26, which was
      shown to ubiquitylate TAF7 and thereby to target it for proteasomal degradation.
      Sustained exposure of cells to TGF-beta resulted in recovery from proliferative
      arrest in association with amplification of the Myc proto-oncogene, with MYC
      inhibiting TRIM26 induction by TGF-beta. Our data thus show that TFIID is not
      simply a general mediator of transcription but contributes to the regulation of
      transcription in response to cell stimulation, playing a key role in the
      cytostatic function of TGF-beta.

PMID- 29203641
TI  - Shp2-Mitogen-Activated Protein Kinase Signaling Drives Proliferation during
      Zebrafish Embryo Caudal Fin Fold Regeneration.
AB  - Regeneration of the zebrafish caudal fin following amputation occurs through
      wound healing, followed by formation of a blastema, which produces cells to
      replace the lost tissue in the final phase of regenerative outgrowth. We show
      that ptpn11a-/- ptpn11b-/- zebrafish embryos, lacking functional Shp2, fail to
      regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a
      functional signaling role, requiring its catalytic activity and SH2 domains but
      not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression
      of Shp2a variants with increased and reduced catalytic activity, respectively,
      rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and
      junbb, indicative of formation of the wound epidermis and distal blastema,
      respectively, suggested that these processes occurred in ptpn11a-/- ptpn11b-/-
      zebrafish embryos. However, cell proliferation and MAPK phosphorylation were
      reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos
      phenocopied loss of Shp2. Our results suggest an essential role for Shp2a-mitogen
      activated protein kinase (MAPK) signaling in promoting cell proliferation during
      zebrafish embryo caudal fin fold regeneration.

PMID- 29203642
TI  - Nuclear Phosphatidylinositol-Phosphate Type I Kinase alpha-Coupled Star-PAP
      Polyadenylation Regulates Cell Invasion.
AB  - Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase
      (PAP), couples with type I PI phosphate kinase alpha (PIPKIalpha) and controls
      gene expression. We show that Star-PAP and PIPKIalpha together regulate 3'-end
      processing and expression of pre-mRNAs encoding key anti-invasive factors
      (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the
      endogenous Star-PAP level is negatively correlated with the cellular invasiveness
      of breast cancer cells. While silencing Star-PAP or PIPKIalpha increases cellular
      invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases
      invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level
      dependent manner. However, expression of the PIPKIalpha-noninteracting Star-PAP
      mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular
      invasiveness. These results strongly indicate that PIPKIalpha interaction and
      Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of
      cancer cell invasion and give specificity to target anti-invasive gene
      expression. Our study establishes Star-PAP-PIPKIalpha-mediated 3'-end processing
      as a key anti-invasive mechanism in breast cancer.

PMID- 29203643
TI  - The N-Terminal CCHC Zinc Finger Motif Mediates Homodimerization of Transcription
      Factor BCL11B.
AB  - The BCL11B gene encodes a Kruppel-like, sequence-specific zinc finger (ZF)
      transcription factor that acts as either a repressor or an activator, depending
      on its posttranslational modifications. The importance of BCL11B in numerous
      biological processes in multiple organs has been well established in mouse
      knockout models. The phenotype of the first de novo monoallelic germ line
      missense mutation in the BCL11B gene (encoding N441K) strongly implies that the
      mutant protein acts in a dominant-negative manner by neutralizing the unaffected
      protein through the formation of a nonfunctional dimer. Using a Forster resonance
      energy transfer-assisted fluorescence-activated cell sorting (FACS-FRET) assay
      and affinity purification followed by mass spectrometry (AP-MS), we show that the
      N-terminal CCHC zinc finger motif is necessary and sufficient for the formation
      of the BCL11B dimer. Mutation of the CCHC ZF in BCL11B abolishes its
      transcription-regulatory activity. In addition, unlike wild-type BCL11B, this
      mutant is incapable of inducing cell cycle arrest and protecting against DNA
      damage-driven apoptosis. Our results confirm the BCL11B dimerization hypothesis
      and prove its importance for BCL11B function. By mapping the relevant regions to
      the CCHC domain, we describe a previously unidentified mechanism of transcription
      factor homodimerization.

PMID- 29203644
TI  - CITED2 restrains pro-inflammatory macrophage activation and response.
AB  - Macrophages are strategically distributed in mammalian tissues and play an
      essential role in priming immune response. However, macrophages need to
      constantly strike a balance between activation and inhibition state to avoid a
      futile inflammatory reaction. Herein, we identify the CBP/p300-interacting
      transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2
      (CITED2) as a potent repressor of macrophage pro-inflammatory activation. Gain-
      and loss-of-function studies revealed that CITED2 is required for optimal
      peroxisome proliferator-activated receptor gamma (PPARgamma) activation and
      attendant select anti-inflammatory gene expression in macrophages. More
      importantly, deficiency of CITED2 resulted in significant attenuation in
      rosiglitazone-induced PPARgamma activity, PPARgamma recruitment to target gene
      promoters and anti-inflammatory target gene expression in macrophages.
      Interestingly, deficiency of Cited2 strikingly heightened pro-inflammatory gene
      expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1alpha)
      protein in macrophages. Further, overexpression of Egln3 or inhibition of
      HIF1alpha in Cited2-deficient macrophages completely reversed elevated pro
      inflammatory cytokine/chemokine gene expression. Importantly, mice bearing a
      myeloid-specific deletion of Cited2 were highly susceptible to endotoxin-induced
      sepsis symptomatology and mortality. Collectively, our observations identify
      CITED2 as a novel negative regulator of macrophage pro-inflammatory activation
      and protect the host from inflammatory insults.

PMID- 29203645
TI  - Downstream promoter interactions of TFIID TAFs facilitate transcription
      reinitiation.
AB  - TFIID binds promoter DNA to recruit RNA polymerase II and other basal factors for
      transcription. Although the TATA-binding protein (TBP) subunit of TFIID is
      necessary and sufficient for in vitro transcription, the TBP-associated factor
      (TAF) subunits recognize downstream promoter elements, act as coactivators, and
      interact with nucleosomes. In yeast nuclear extracts, transcription induces
      stable TAF binding to downstream promoter DNA, promoting subsequent activator
      independent transcription reinitiation. In vivo, promoter responses to TAF
      mutations correlate with the level of downstream, rather than overall, Taf1 cross
      linking. We propose a new model in which TAFs function as reinitiation factors,
      accounting for the differential responses of promoters to various transcription
      factor mutations.

PMID- 29203646
TI  - Structural and biochemical characterization of the catalytic domains of GdpP
      reveals a unified hydrolysis mechanism for the DHH/DHHA1 phosphodiesterase.
AB  - The Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing
      phosphodiesterases (PDEs) that catalyze degradation of cyclic di-adenosine
      monophosphate (c-di-AMP) could be subdivided into two subfamilies based on the
      final product [5'-phosphadenylyl-adenosine (5'-pApA) or AMP]. In a previous
      study, we revealed that Rv2837c, a stand-alone DHH/DHHA1 PDE, employs a 5'-pApA
      internal flipping mechanism to produce AMPs. However, why the membrane-bound
      DHH/DHHA1 PDE can only degrade c-di-AMP to 5'-pApA remains obscure. Here, we
      report the crystal structure of the DHH/DHHA1 domain of GdpP (GdpP-C), and
      structures in complex with c-di-AMP, cyclic di-guanosine monophosphate (c-di
      GMP), and 5'-pApA. Structural analysis reveals that GdpP-C binds nucleotide
      substrates quite differently from how Rv2837c does in terms of substrate-binding
      position. Accordingly, the nucleotide-binding site of the DHH/DHHA1 PDEs is
      organized into three (C, G, and R) subsites. For GdpP-C, in the C and G sites c
      di-AMP binds and degrades into 5'-pApA, and its G site determines nucleotide
      specificity. To further degrade into AMPs, 5'-pApA must slide into the C and R
      sites for flipping and hydrolysis as in Rv2837c. Subsequent mutagenesis and
      enzymatic studies of GdpP-C and Rv2837c uncover the complete flipping process and
      reveal a unified catalytic mechanism for members of both DHH/DHHA1 PDE
      subfamilies.

PMID- 29203647
TI  - Molecular basis for the integration of environmental signals by FurB from
      Anabaena sp. PCC 7120.
AB  - FUR (Ferric uptake regulator) proteins are among the most important families of
      transcriptional regulators in prokaryotes, often behaving as global regulators.
      In the cyanobacterium Anabaena PCC 7120, FurB (Zur, Zinc uptake regulator)
      controls zinc and redox homeostasis through the repression of target genes in a
      zinc-dependent manner. In vitro, non-specific binding of FurB to DNA elicits
      protection against oxidative damage and avoids cleavage by deoxyribonuclease I.
      The present study provides, for the first time, evidence of the influence of
      redox environment in the interaction of FurB with regulatory zinc and its
      consequences in FurB-DNA-binding affinity. Calorimetry studies showed that, in
      addition to one structural Zn(II), FurB is able to bind two additional Zn(II) per
      monomer and demonstrated the implication of cysteine C93 in regulatory Zn(II)
      coordination. The interaction of FurB with the second regulatory zinc occurred
      only under reducing conditions. While non-specific FurB-DNA interaction is Zn(II)
      independent, the optimal binding of FurB to target promoters required loading of
      two regulatory zinc ions. Those results combined with site-directed mutagenesis
      and gel-shift assays evidenced that the redox state of cysteine C93 conditions
      the binding of the second regulatory Zn(II) and, in turn, modulates the affinity
      for a specific DNA target. Furthermore, differential spectroscopy studies showed
      that cysteine C93 could also be involved in heme coordination by FurB, either as
      a direct ligand or being located near the binding site. The results indicate that
      besides controlling zinc homeostasis, FurB could work as a redox-sensing protein
      probably modifying its zinc and DNA-binding abilities depending upon
      environmental conditions.

PMID- 29203648
TI  - Musical training sharpens and bonds ears and tongue to hear speech better.
AB  - The idea that musical training improves speech perception in challenging
      listening environments is appealing and of clinical importance, yet the
      mechanisms of any such musician advantage are not well specified. Here, using
      functional magnetic resonance imaging (fMRI), we found that musicians
      outperformed nonmusicians in identifying syllables at varying signal-to-noise
      ratios (SNRs), which was associated with stronger activation of the left inferior
      frontal and right auditory regions in musicians compared with nonmusicians.
      Moreover, musicians showed greater specificity of phoneme representations in
      bilateral auditory and speech motor regions (e.g., premotor cortex) at higher
      SNRs and in the left speech motor regions at lower SNRs, as determined by
      multivoxel pattern analysis. Musical training also enhanced the intrahemispheric
      and interhemispheric functional connectivity between auditory and speech motor
      regions. Our findings suggest that improved speech in noise perception in
      musicians relies on stronger recruitment of, finer phonological representations
      in, and stronger functional connectivity between auditory and frontal speech
      motor cortices in both hemispheres, regions involved in bottom-up spectrotemporal
      analyses and top-down articulatory prediction and sensorimotor integration,
      respectively.

PMID- 29203649
TI  - pH-sensitive vibrational probe reveals a cytoplasmic protonated cluster in
      bacteriorhodopsin.
AB  - Infrared spectroscopy has been used in the past to probe the dynamics of internal
      proton transfer reactions taking place during the functional mechanism of
      proteins but has remained mostly silent to protonation changes in the aqueous
      medium. Here, by selectively monitoring vibrational changes of buffer molecules
      with a temporal resolution of 6 us, we have traced proton release and uptake
      events in the light-driven proton-pump bacteriorhodopsin and correlate these to
      other molecular processes within the protein. We demonstrate that two distinct
      chemical entities contribute to the temporal evolution and spectral shape of the
      continuum band, an unusually broad band extending from 2,300 to well below 1,700
      cm-1 The first contribution corresponds to deprotonation of the proton release
      complex (PRC), a complex in the extracellular domain of bacteriorhodopsin where
      an excess proton is shared by a cluster of internal water molecules and/or ionic
      E194/E204 carboxylic groups. We assign the second component of the continuum band
      to the proton uptake complex, a cluster with an excess proton reminiscent to the
      PRC but located in the cytoplasmic domain and possibly stabilized by D38. Our
      findings refine the current interpretation of the continuum band and call for a
      reevaluation of the last proton transfer steps in bacteriorhodopsin.

PMID- 29203650
TI  - Point-of-care device to diagnose and monitor neonatal jaundice in low-resource
      settings.
AB  - Newborns are at increased risk of jaundice, a condition in which excess bilirubin
      accumulates in blood. Left untreated, jaundice can lead to neurological
      impairment and death. Jaundice resulting from unconjugated hyperbilirubinemia is
      easily treated with exposure to blue light, and phototherapy systems have been
      developed for low-resource settings; however, there are no appropriate solutions
      to diagnose and monitor jaundice in these settings. To address this need we
      present BiliSpec, a low-cost reader and disposable lateral flow card designed to
      measure the concentration of total bilirubin from several drops of blood at the
      point of care. We evaluated the performance of BiliSpec, using blood from normal
      volunteers spiked with varying amounts of bilirubin; results measured using
      BiliSpec correlated well with a reference laboratory bilirubinometer (r = 0.996).
      We then performed a pilot clinical study using BiliSpec to measure total
      bilirubin in neonates at risk for jaundice at Queen Elizabeth Central Hospital in
      Blantyre, Malawi. Concentrations measured using BiliSpec correlated well with
      those measured using a laboratory reference standard in 94 patient samples
      ranging from 1.1 mg/dL to 23.0 mg/dL in concentration (r = 0.973). The mean
      difference between bilirubin levels measured with BiliSpec and the reference
      standard was 0.3 mg/dL (95[Formula: see text] CI: -1.7-2.2 mg/dL).

PMID- 29203651
TI  - Development and validation of a high-throughput transcriptomic biomarker to
      address 21st century genetic toxicology needs.
AB  - Interpretation of positive genotoxicity findings using the current in vitro
      testing battery is a major challenge to industry and regulatory agencies. These
      tests, especially mammalian cell assays, have high sensitivity but suffer from
      low specificity, leading to high rates of irrelevant positive findings (i.e.,
      positive results in vitro that are not relevant to human cancer hazard). We
      developed an in vitro transcriptomic biomarker-based approach that provides
      biological relevance to positive genotoxicity assay data, particularly for in
      vitro chromosome damage assays, and propose its application for assessing the
      relevance of the in vitro positive results to carcinogenic hazard. The
      transcriptomic biomarker TGx-DDI (previously known as TGx-28.65) readily
      distinguishes DNA damage-inducing (DDI) agents from non-DDI agents. In this
      study, we demonstrated the ability of the biomarker to classify 45 test agents
      across a broad set of chemical classes as DDI or non-DDI. Furthermore, we
      assessed the biomarker's utility in derisking known irrelevant positive agents
      and evaluated its performance across analytical platforms. We correctly
      classified 90% (9 of 10) of chemicals with irrelevant positive findings in in
      vitro chromosome damage assays as negative. We developed a standardized
      experimental and analytical protocol for our transcriptomics biomarker, as well
      as an enhanced application of TGx-DDI for high-throughput cell-based genotoxicity
      testing using nCounter technology. This biomarker can be integrated in genetic
      hazard assessment as a follow-up to positive chromosome damage findings. In
      addition, we propose how it might be used in chemical screening and assessment.
      This approach offers an opportunity to significantly improve risk assessment and
      reduce cost.

PMID- 29203652
TI  - Divergence of regulatory networks governed by the orthologous transcription
      factors FLC and PEP1 in Brassicaceae species.
AB  - Genome-wide landscapes of transcription factor (TF) binding sites (BSs) diverge
      during evolution, conferring species-specific transcriptional patterns. The rate
      of divergence varies in different metazoan lineages but has not been widely
      studied in plants. We identified the BSs and assessed the effects on
      transcription of FLOWERING LOCUS C (FLC) and PERPETUAL FLOWERING 1 (PEP1), two
      orthologous MADS-box TFs that repress flowering and confer vernalization
      requirement in the Brassicaceae species Arabidopsis thaliana and Arabis alpina,
      respectively. We found that only 14% of their BSs were conserved in both species
      and that these contained a CArG-box that is recognized by MADS-box TFs. The CArG
      box consensus at conserved BSs was extended compared with the core motif. By
      contrast, species-specific BSs usually lacked the CArG-box in the other species.
      Flowering-time genes were highly overrepresented among conserved targets, and
      their CArG-boxes were widely conserved among Brassicaceae species. Cold-regulated
      (COR) genes were also overrepresented among targets, but the cognate BSs and the
      identity of the regulated genes were usually different in each species. In cold,
      COR gene transcript levels were increased in flc and pep1-1 mutants compared with
      WT, and this correlated with reduced growth in pep1-1 Therefore, FLC orthologs
      regulate a set of conserved target genes mainly involved in reproductive
      development and were later independently recruited to modulate stress responses
      in different Brassicaceae lineages. Analysis of TF BSs in these lineages thus
      distinguishes widely conserved targets representing the core function of the TF
      from those that were recruited later in evolution.

PMID- 29203653
TI  - Rapid diagnostic testing platform for iron and vitamin A deficiency.
AB  - Micronutrient deficiencies such as those of vitamin A and iron affect a third of
      the world's population with consequences such as night blindness, higher child
      mortality, anemia, poor pregnancy outcomes, and reduced work capacity. Many
      efforts to prevent or treat these deficiencies are hampered by the lack of
      adequate, accessible, and affordable diagnostic methods that can enable better
      targeting of interventions. In this work, we demonstrate a rapid diagnostic test
      and mobile enabled platform for simultaneously quantifying iron (ferritin),
      vitamin A (retinol-binding protein), and inflammation (C-reactive protein)
      status. Our approach, enabled by combining multiple florescent markers and
      immunoassay approaches on a single test, allows us to provide accurate
      quantification in 15 min even though the physiological range of the markers of
      interest varies over five orders of magnitude. We report sensitivities of 88%,
      100%, and 80% and specificities of 97%, 100%, and 97% for iron deficiency
      (ferritin <15 ng/mL or 32 pmol/L), vitamin A deficiency (retinol-binding protein
      <14.7 MUg/mL or 0.70 MUmol/L) and inflammation status (C-reactive protein >3.0
      MUg/mL or 120 nmol/L), respectively. This technology is suitable for point-of
      care use in both resource-rich and resource-limited settings and can be read
      either by a standard laptop computer or through our previously developed
      NutriPhone technology. If implemented as either a population-level screening or
      clinical diagnostic tool, we believe this platform can transform nutritional
      status assessment and monitoring globally.

PMID- 29203654
TI  - Relationship between season of birth, temperature exposure, and later life
      wellbeing.
AB  - We study how exposure to extreme temperatures in early periods of child
      development is related to adult economic outcomes measured 30 y later. Our
      analysis uses administrative earnings records for over 12 million individuals
      born in the United States between 1969 and 1977, linked to fine-scale, daily
      weather data and location and date of birth. We calculate the length of time each
      individual is exposed to different temperatures in utero and in early childhood,
      and we estimate flexible regression models that allow for nonlinearities in the
      relationship between temperature and long-run outcomes. We find that an extra day
      with mean temperatures above 32  degrees C in utero and in the first year after
      birth is associated with a 0.1% reduction in adult annual earnings at age 30.
      Temperature sensitivity is evident in multiple periods of early development,
      ranging from the first trimester of gestation to age 6-12 mo. We observe that
      household air-conditioning adoption, which increased dramatically over the time
      period studied, mitigates nearly all of the estimated temperature sensitivity.

PMID- 29203655
TI  - Evaluating the environmental impacts of dietary recommendations.
AB  - Dietary choices drive both health and environmental outcomes. Information on
      diets come from many sources, with nationally recommended diets (NRDs) by
      governmental or similar advisory bodies the most authoritative. Little or no
      attention is placed on the environmental impacts within NRDs. Here we quantify
      the impact of nation-specific NRDs, compared with an average diet in 37 nations,
      representing 64% of global population. We focus on greenhouse gases (GHGs),
      eutrophication, and land use because these have impacts reaching or exceeding
      planetary boundaries. We show that compared with average diets, NRDs in high
      income nations are associated with reductions in GHG, eutrophication, and land
      use from 13.0 to 24.8%, 9.8 to 21.3%, and 5.7 to 17.6%, respectively. In upper
      middle-income nations, NRDs are associated with slight decrease in impacts of 0.8
      12.2%, 7.7-19.4%, and 7.2-18.6%. In poorer middle-income nations, impacts
      increase by 12.4-17.0%, 24.5-31.9%, and 8.8-14.8%. The reduced environmental
      impact in high-income countries is driven by reductions in calories (~54% of
      effect) and a change in composition (~46%). The increased environmental impacts
      of NRDs in low- and middle-income nations are associated with increased intake in
      animal products. Uniform adoption of NRDs across these nations would result in
      reductions of 0.19-0.53 Gt CO2 eq?a-1, 4.32-10.6 Gt [Formula: see text] eq?a-1,
      and 1.5-2.8 million km2, while providing the health cobenefits of adopting an
      NRD. As a small number of dietary guidelines are beginning to incorporate more
      general environmental concerns, we anticipate that this work will provide a
      standardized baseline for future work to optimize recommended diets further.

PMID- 29203657
TI  - Percolative core formation in planetesimals enabled by hysteresis in metal
      connectivity.
AB  - The segregation of dense core-forming melts by porous flow is a natural mechanism
      for core formation in early planetesimals. However, experimental observations
      show that texturally equilibrated metallic melt does not wet the silicate grain
      boundaries and tends to reside in isolated pockets that prevent percolation. Here
      we use pore-scale simulations to determine the minimum melt fraction required to
      induce porous flow, the percolation threshold. The composition of terrestrial
      planets suggests that typical planetesimals contain enough metal to overcome this
      threshold. Nevertheless, it is currently thought that melt segregation is
      prevented by a pinch-off at melt fractions slightly below the percolation
      threshold. In contrast to previous work, our simulations on irregular grain
      geometries reveal that a texturally equilibrated melt network remains connected
      down to melt fractions of only 1 to 2%. This hysteresis in melt connectivity
      allows percolative core formation in planetesimals that contain enough metal to
      exceed the percolation threshold. Evidence for the percolation of metallic melt
      is provided by X-ray microtomography of primitive achondrite Northwest Africa
      (NWA) 2993. Microstructural analysis shows that the metal-silicate interface has
      characteristics expected for a texturally equilibrated pore network with a
      dihedral angle of ~85 degrees . The melt network therefore remained close to
      textural equilibrium despite a complex history. This suggests that the hysteresis
      in melt connectivity is a viable process for percolative core formation in the
      parent bodies of primitive achondrites.

PMID- 29203656
TI  - Enigmatic origin of the poxvirus membrane from the endoplasmic reticulum shown by
      3D imaging of vaccinia virus assembly mutants.
AB  - The long-standing inability to visualize connections between poxvirus membranes
      and cellular organelles has led to uncertainty regarding the origin of the viral
      membrane. Indeed, there has been speculation that viral membranes form de novo in
      cytoplasmic factories. Another possibility, that the connections are too short
      lived to be captured by microscopy during a normal infection, motivated us to
      identify and characterize virus mutants that are arrested in assembly. Five
      conserved vaccinia virus proteins, referred to as Viral Membrane Assembly
      Proteins (VMAPs), that are necessary for formation of immature virions were
      found. Transmission electron microscopy studies of two VMAP deletion mutants had
      suggested retention of connections between viral membranes and the endoplasmic
      reticulum (ER). We now analyzed cells infected with each of the five VMAP
      deletion mutants by electron tomography, which is necessary to validate membrane
      continuity, in addition to conventional transmission electron microscopy. In all
      cases, connections between the ER and viral membranes were demonstrated by 3D
      reconstructions, supporting a role for the VMAPs in creating and/or stabilizing
      membrane scissions. Furthermore, coexpression of the viral reticulon-like
      transmembrane protein A17 and the capsid-like scaffold protein D13 was sufficient
      to form similar ER-associated viral structures in the absence of other major
      virion proteins. Determination of the mechanism of ER disruption during a normal
      VACV infection and the likely participation of both viral and cell proteins in
      this process may provide important insights into membrane dynamics.

PMID- 29203658
TI  - Molecular and functional resemblance of differentiated cells derived from
      isogenic human iPSCs and SCNT-derived ESCs.
AB  - Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear
      reprogramming by transcription factors (i.e., induced pluripotent stem cells,
      iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and
      preclinical application of differentiated cells generated by different
      reprogramming mechanisms have yet to be evaluated. Here we investigated the
      molecular and functional features, and drug response of cardiomyocytes (PSC-CMs)
      and endothelial cells (PSC-ECs) derived from genetically relevant sets of human
      iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro
      fertilization embryo-derived ESCs (IVF-ESCs). We found that differentiated cells
      derived from isogenic iPSCs and nt-ESCs showed comparable lineage gene
      expression, cellular heterogeneity, physiological properties, and metabolic
      functions. Genome-wide transcriptome and DNA methylome analysis indicated that
      iPSC derivatives (iPSC-CMs and iPSC-ECs) were more similar to isogenic nt-ESC
      counterparts than those derived from IVF-ESCs. Although iPSCs and nt-ESCs shared
      the same nuclear DNA and yet carried different sources of mitochondrial DNA, CMs
      derived from iPSC and nt-ESCs could both recapitulate doxorubicin-induced
      cardiotoxicity and exhibited insignificant differences on reactive oxygen species
      generation in response to stress condition. We conclude that molecular and
      functional characteristics of differentiated cells from human PSCs are primarily
      attributed to the genetic compositions rather than the reprogramming mechanisms
      (SCNT vs. iPSCs). Therefore, human iPSCs can replace nt-ESCs as alternatives for
      generating patient-specific differentiated cells for disease modeling and
      preclinical drug testing.

PMID- 29203659
TI  - TRPV1 is a physiological regulator of MU-opioid receptors.
AB  - Opioids are powerful analgesics, but also carry significant side effects and
      abuse potential. Here we describe a modulator of the MU-opioid receptor (MOR1),
      the transient receptor potential channel subfamily vanilloid member 1 (TRPV1). We
      show that TRPV1 binds MOR1 and blocks opioid-dependent phosphorylation of MOR1
      while leaving G protein signaling intact. Phosphorylation of MOR1 initiates
      recruitment and activation of the beta-arrestin pathway, which is responsible for
      numerous opioid-induced adverse effects, including the development of tolerance
      and respiratory depression. Phosphorylation stands in contrast to G protein
      signaling, which is responsible for the analgesic effect of opioids. Calcium
      influx through TRPV1 causes a calcium/calmodulin-dependent translocation of G
      protein-coupled receptor kinase 5 (GRK5) away from the plasma membrane, thereby
      blocking its ability to phosphorylate MOR1. Using TRPV1 to block phosphorylation
      of MOR1 without affecting G protein signaling is a potential strategy to improve
      the therapeutic profile of opioids.

PMID- 29203660
TI  - Terminal attack trajectories of peregrine falcons are described by the
      proportional navigation guidance law of missiles.
AB  - The ability to intercept uncooperative targets is key to many diverse flight
      behaviors, from courtship to predation. Previous research has looked for simple
      geometric rules describing the attack trajectories of animals, but the underlying
      feedback laws have remained obscure. Here, we use GPS loggers and onboard video
      cameras to study peregrine falcons, Falco peregrinus, attacking stationary
      targets, maneuvering targets, and live prey. We show that the terminal attack
      trajectories of peregrines are not described by any simple geometric rule as
      previously claimed, and instead use system identification techniques to fit a
      phenomenological model of the dynamical system generating the observed
      trajectories. We find that these trajectories are best-and exceedingly well
      modeled by the proportional navigation (PN) guidance law used by most guided
      missiles. Under this guidance law, turning is commanded at a rate proportional to
      the angular rate of the line-of-sight between the attacker and its target, with a
      constant of proportionality (i.e., feedback gain) called the navigation constant
      (N). Whereas most guided missiles use navigation constants falling on the
      interval 3 <= N <= 5, peregrine attack trajectories are best fitted by lower
      navigation constants (median N < 3). This lower feedback gain is appropriate at
      the lower flight speed of a biological system, given its presumably higher error
      and longer delay. This same guidance law could find use in small visually guided
      drones designed to remove other drones from protected airspace.

PMID- 29203661
TI  - Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors.
AB  - Histone deacetylases (HDACs) regulate myriad cellular processes by catalyzing the
      hydrolysis of acetyl-l-lysine residues in histone and nonhistone proteins. The
      Zn2+-dependent class IIb enzyme HDAC6 regulates microtubule function by
      deacetylating alpha-tubulin, which suppresses microtubule dynamics and leads to
      cell cycle arrest and apoptosis. Accordingly, HDAC6 is a target for the
      development of selective inhibitors that might be useful in new therapeutic
      approaches for the treatment of cancer, neurodegenerative diseases, and other
      disorders. Here, we present high-resolution structures of catalytic domain 2 from
      Danio rerio HDAC6 (henceforth simply "HDAC6") complexed with compounds that
      selectively inhibit HDAC6 while maintaining nanomolar inhibitory potency: N
      hydroxy-4-[(N(2-hydroxyethyl)-2-phenylacetamido)methyl)-benzamide)] (HPB), ACY
      1215 (Ricolinostat), and ACY-1083. These structures reveal that an unusual
      monodentate Zn2+ coordination mode is exploited by sterically bulky HDAC6
      selective phenylhydroxamate inhibitors. We additionally report the ultrahigh
      resolution structure of the HDAC6-trichostatin A complex, which reveals two Zn2+
      binding conformers for the inhibitor: a major conformer (70%) with canonical
      bidentate hydroxamate-Zn2+ coordination geometry and a minor conformer (30%) with
      monodentate hydroxamate-Zn2+ coordination geometry, reflecting a free energy
      difference of only 0.5 kcal/mol. The minor conformer is not visible in lower
      resolution structure determinations. Structural comparisons of HDAC6-inhibitor
      complexes with class I HDACs suggest active site features that contribute to the
      isozyme selectivity observed in biochemical assays.

PMID- 29203662
TI  - Methylprednisolone acetate induces, and Delta7-dafachronic acid suppresses,
      Strongyloides stercoralis hyperinfection in NSG mice.
AB  - Strongyloides stercoralis hyperinfection causes high mortality rates in humans,
      and, while hyperinfection can be induced by immunosuppressive glucocorticoids,
      the pathogenesis remains unknown. Since immunocompetent mice are resistant to
      infection with S. stercoralis, we hypothesized that NSG mice, which have a
      reduced innate immune response and lack adaptive immunity, would be susceptible
      to the infection and develop hyperinfection. Interestingly, despite the presence
      of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG
      mice, no hyperinfection was observed even when the mice were treated with a
      monoclonal antibody to eliminate residual granulocyte activity. NSG mice were
      then infected with third-stage larvae and treated for 6 wk with
      methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of
      infected mice resulted in 50% mortality and caused a significant >10-fold
      increase in the number of parasitic female worms compared with infected untreated
      mice. In addition, autoinfective third-stage larvae, which initiate
      hyperinfection, were found in high numbers in MPA-treated, but not untreated,
      mice. Remarkably, treatment with Delta7-dafachronic acid, an agonist of the
      parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA
      treated mice undergoing hyperinfection with S. stercoralis Overall, this study
      provides a useful mouse model for S. stercoralis autoinfection and suggests a
      therapeutic strategy for treating lethal hyperinfection.

PMID- 29203663
TI  - Selected reaction monitoring approach for validating peptide biomarkers.
AB  - We here describe a selected reaction monitoring (SRM)-based approach for the
      discovery and validation of peptide biomarkers for cancer. The first stage of
      this approach is the direct identification of candidate peptides through
      comparison of proteolytic peptides derived from the plasma of cancer patients or
      healthy individuals. Several hundred candidate peptides were identified through
      this method, providing challenges for choosing and validating the small number of
      peptides that might prove diagnostically useful. To accomplish this validation,
      we used 2D chromatography coupled with SRM of candidate peptides. We applied this
      approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM),
      to plasma from cancer patients and discovered two peptides encoded by the
      peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased
      in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels
      of at least one of these two peptides was detected in 43 (68.3%) of 63 women with
      ovarian cancer but in none of 50 healthy controls. In addition to providing a
      potential biomarker for ovarian cancer, this approach is generally applicable to
      the discovery of peptides characteristic of various disease states.

PMID- 29203664
TI  - Structural insights into how GTP-dependent conformational changes in a
      metallochaperone UreG facilitate urease maturation.
AB  - The ability of metallochaperones to allosterically regulate the binding/release
      of metal ions and to switch protein-binding partners along the metal delivery
      pathway is essential to the metallation of the metalloenzymes. Urease, catalyzing
      the hydrolysis of urea into ammonia and carbon dioxide, contains two nickel ions
      bound by a carbamylated lysine in its active site. Delivery of nickel ions for
      urease maturation is dependent on GTP hydrolysis and is assisted by four urease
      accessory proteins UreE, UreF, UreG, and UreH(UreD). Here, we determined the
      crystal structure of the UreG dimer from Klebsiella pneumoniae in complex with
      nickel and GMPPNP, a nonhydrolyzable analog of GTP. Comparison with the structure
      of the GDP-bound Helicobacter pylori UreG (HpUreG) in the UreG2F2H2 complex
      reveals large conformational changes in the G2 region and residues near the
      66CPH68 metal-binding motif. Upon GTP binding, the side chains of Cys66 and His68
      from each of the UreG protomers rotate toward each other to coordinate a nickel
      ion in a square-planar geometry. Mutagenesis studies on HpUreG support the
      conformational changes induced by GTP binding as essential to dimerization of
      UreG, GTPase activity, in vitro urease activation, and the switching of UreG from
      the UreG2F2H2 complex to form the UreE2G2 complex with the UreE dimer. The nickel
      charged UreE dimer, providing the sole source of nickel, and the UreG2F2H2
      complex could activate urease in vitro in the presence of GTP. Based on our
      results, we propose a mechanism of how conformational changes of UreG during the
      GTP hydrolysis/binding cycle facilitate urease maturation.

PMID- 29203666
TI  - Structure and function of a compound eye, more than half a billion years old.
AB  - Until now, the fossil record has not been capable of revealing any details of the
      mechanisms of complex vision at the beginning of metazoan evolution. Here, we
      describe functional units, at a cellular level, of a compound eye from the base
      of the Cambrian, more than half a billion years old. Remains of early Cambrian
      arthropods showed the external lattices of enormous compound eyes, but not the
      internal structures or anything about how those compound eyes may have
      functioned. In a phosphatized trilobite eye from the lower Cambrian of the
      Baltic, we found lithified remnants of cellular systems, typical of a modern
      focal apposition eye, similar to those of a bee or dragonfly. This shows that
      sophisticated eyes already existed at the beginning of the fossil record of
      higher organisms, while the differences between the ancient system and the
      internal structures of a modern apposition compound eye open important insights
      into the evolution of vision.

PMID- 29203665
TI  - Structural studies of Chikungunya virus maturation.
AB  - Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3
      glycoproteins before assembly with the nucleocapsid is the key to producing
      fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-A
      resolution structure of an "immature" Chikungunya virus in which the cleavage
      site has been mutated to inhibit proteolysis. The spikes in the immature virus
      have a larger radius and are less compact than in the mature virus. Furthermore,
      domains B on the E2 glycoproteins have less freedom of movement in the immature
      virus, keeping the fusion loops protected under domain B. In addition, the
      nucleocapsid of the immature virus is more compact than in the mature virus,
      protecting a conserved ribosome-binding site in the capsid protein from exposure.
      These differences suggest that the posttranslational processing of the spikes and
      nucleocapsid is necessary to produce infectious virus.

PMID- 29203667
TI  - Electrostatic confinement and manipulation of DNA molecules for genome analysis.
AB  - Very large DNA molecules enable comprehensive analysis of complex genomes, such
      as human, cancer, and plants because they span across sequence repeats and
      complex somatic events. When physically manipulated, or analyzed as single
      molecules, long polyelectrolytes are problematic because of mechanical
      considerations that include shear-mediated breakage, dealing with the massive
      size of these coils, or the length of stretched DNAs using common experimental
      techniques and fluidic devices. Accordingly, we harness analyte "issues" as
      exploitable advantages by our invention and characterization of the "molecular
      gate," which controls and synchronizes formation of stretched DNA molecules as
      DNA dumbbells within nanoslit geometries. Molecular gate geometries comprise
      micro- and nanoscale features designed to synergize very low ionic strength
      conditions in ways we show effectively create an "electrostatic bottle." This
      effect greatly enhances molecular confinement within large slit geometries and
      supports facile, synchronized electrokinetic loading of nanoslits, even without
      dumbbell formation. Device geometries were considered at the molecular and
      continuum scales through computer simulations, which also guided our efforts to
      optimize design and functionalities. In addition, we show that the molecular gate
      may govern DNA separations because DNA molecules can be electrokinetically
      triggered, by varying applied voltage, to enter slits in a size-dependent manner.
      Lastly, mapping the Mesoplasmaflorum genome, via synchronized dumbbell formation,
      validates our nascent approach as a viable starting point for advanced
      development that will build an integrated system capable of large-scale genome
      analysis.

PMID- 29203668
TI  - Epigenetic therapy activates type I interferon signaling in murine ovarian cancer
      to reduce immunosuppression and tumor burden.
AB  - Ovarian cancer is the most lethal of all gynecological cancers, and there is an
      urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is
      characterized by an immune suppressive microenvironment, and response of ovarian
      cancers to immune therapies has thus far been disappointing. We now find, in a
      mouse model of EOC, that clinically relevant doses of DNA methyltransferase and
      histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune
      suppressive microenvironment through type I IFN signaling and improve response to
      immune checkpoint therapy. These data indicate that the type I IFN response is
      required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine
      (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune
      cells and the percentage of active CD8+ T and natural killer (NK) cells in the
      tumor microenvironment, while reducing tumor burden and extending survival. AZA
      also increases viral defense gene expression in both tumor and immune cells, and
      reduces the percentage of macrophages and myeloid-derived suppressor cells in the
      tumor microenvironment. The addition of an HDACi to AZA enhances the modulation
      of the immune microenvironment, specifically increasing T and NK cell activation
      and reducing macrophages over AZA treatment alone, while further increasing the
      survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the
      immune checkpoint inhibitor alpha-PD-1 provides the best antitumor effect and
      longest overall survival, and may be an attractive candidate for future clinical
      trials in ovarian cancer.

PMID- 29203669
TI  - Islet cells share promoter hypomethylation independently of expression, but
      exhibit cell-type-specific methylation in enhancers.
AB  - DNA methylation at promoters is an important determinant of gene expression.
      Earlier studies suggested that the insulin gene promoter is uniquely unmethylated
      in insulin-expressing pancreatic beta-cells, providing a classic example of this
      paradigm. Here we show that islet cells expressing insulin, glucagon, or
      somatostatin share a lack of methylation at the promoters of the insulin and
      glucagon genes. This is achieved by rapid demethylation of the insulin and
      glucagon gene promoters during differentiation of Neurogenin3+ embryonic
      endocrine progenitors, regardless of the specific endocrine cell-type chosen.
      Similar methylation dynamics were observed in transgenic mice containing a human
      insulin promoter fragment, pointing to the responsible cis element. Whole
      methylome comparison of human alpha- and beta-cells revealed generality of the
      findings: genes active in one cell type and silent in the other tend to share
      demethylated promoters, while methylation differences between alpha- and beta
      cells are concentrated in enhancers. These findings suggest an epigenetic basis
      for the observed plastic identity of islet cell types, and have implications for
      beta-cell reprogramming in diabetes and diagnosis of beta-cell death using
      methylation patterns of circulating DNA.

PMID- 29203670
TI  - Kras mutant genetically engineered mouse models of human cancers are genomically
      heterogeneous.
AB  - KRAS mutant tumors are largely recalcitrant to targeted therapies. Genetically
      engineered mouse models (GEMMs) of Kras mutant cancer recapitulate critical
      aspects of this disease and are widely used for preclinical validation of targets
      and therapies. Through comprehensive profiling of exomes and matched
      transcriptomes of >200 KrasG12D-initiated GEMM tumors from one lung and two
      pancreatic cancer models, we discover that significant intratumoral and
      intertumoral genomic heterogeneity evolves during tumorigenesis. Known oncogenes
      and tumor suppressor genes, beyond those engineered, are mutated, amplified, and
      deleted. Unlike human tumors, the GEMM genomic landscapes are dominated by copy
      number alterations, while protein-altering mutations are rare. However,
      interspecies comparative analyses of the genomic landscapes demonstrate fidelity
      between genes altered in KRAS mutant human and murine tumors. Genes that are
      spontaneously altered during murine tumorigenesis are also among the most
      prevalent found in human indications. Using targeted therapies, we also
      demonstrate that this inherent tumor heterogeneity can be exploited preclinically
      to discover cancer-specific and genotype-specific therapeutic vulnerabilities.
      Focusing on Kras allelic imbalance, a feature shared by all three models, we
      discover that MAPK pathway inhibition impinges uniquely on this event, indicating
      distinct susceptibility and fitness advantage of Kras-mutant cells. These data
      reveal previously unknown genomic diversity among KrasG12D-initiated GEMM tumors,
      places them in context of human patients, and demonstrates how to exploit this
      inherent tumor heterogeneity to discover therapeutic vulnerabilities.

PMID- 29203671
TI  - Early childhood stress exposure, reward pathways, and adult decision making.
AB  - Individuals who have experienced chronic and high levels of stress during their
      childhoods are at increased risk for a wide range of behavioral problems, yet the
      neurobiological mechanisms underlying this association are poorly understood. We
      measured the life circumstances of a community sample of school-aged children and
      then followed these children for a decade. Those from the highest and lowest
      quintiles of childhood stress exposure were invited to return to our laboratory
      as young adults, at which time we reassessed their life circumstances, acquired
      fMRI data during a reward-processing task, and tested their judgment and decision
      making. Individuals who experienced high levels of early life stress showed lower
      levels of brain activation when processing cues signaling potential loss and
      increased responsivity when actually experiencing losses. Specifically, those
      with high childhood stress had reduced activation in the posterior
      cingulate/precuneus, middle temporal gyrus, and superior occipital cortex during
      the anticipation of potential rewards; reduced activation in putamen and insula
      during the anticipation of potential losses; and increased left inferior frontal
      gyrus activation when experiencing an actual loss. These patterns of brain
      activity were associated with both laboratory and real-world measures of
      individuals' risk taking in adulthood. Importantly, these effects were predicated
      only by childhood stress exposure and not by current levels of life stress.

PMID- 29203672
TI  - Earliest hydraulic enterprise in China, 5,100 years ago.
AB  - Here we present one of the world's oldest examples of large-scale and formalized
      water management, in the case of the Liangzhu culture of the Yangtze Delta, dated
      at 5,300-4,300 years cal B.P. The Liangzhu culture represented a peak of early
      cultural and social development predating the historically recorded Chinese
      dynasties; hence, this study reveals more about the ancient origins of hydraulic
      engineering as a core element of social, political, and economic developments.
      Archaeological surveys and excavations can now portray the impressive extent and
      structure of dams, levees, ditches, and other landscape-transforming features,
      supporting the ancient city of Liangzhu, with an estimated size of about 300 ha.
      The results indicate an enormous collective undertaking, with unprecedented
      evidence for understanding how the city, economy, and society of Liangzhu
      functioned and developed at such a large scale. Concurrent with the evidence of
      technological achievements and economic success, a unique relationship between
      ritual order and social power is seen in the renowned jade objects in Liangzhu
      elite burials, thus expanding our view beyond the practicalities of water
      management and rice farming.

PMID- 29203673
TI  - Evidence for sortilin modulating regional accumulation of human tau prions in
      transgenic mice.
AB  - Misfolding of tau proteins into prions and their propagation along neural
      circuits are thought to result in neurodegeneration causing Alzheimer's disease,
      progressive supranuclear palsy, chronic traumatic encephalopathy, and other
      tauopathies. Little is known about the molecular processes mediating tau prion
      replication and spreading in different brain regions. Using transgenic (Tg) mice
      with a neuronal promoter driving expression of human mutant (P301S) tau, we found
      that tau prion formation and histopathologic deposition is largely restricted to
      the hindbrain. Unexpectedly, tau mRNA and protein levels did not differ between
      the forebrain and hindbrain, suggesting that other factors modulating the
      conversion of tau into a prion exist and are region specific. Using a cell-based
      prion propagation assay, we discovered that tau prion replication is suppressed
      by forebrain-derived inhibitors, one of which is sortilin, a lysosomal sorting
      receptor. We also show that sortilin expression is higher in the forebrain than
      the hindbrain across the life span of the Tg mice, suggesting that sortilin, at
      least in part, inhibits forebrain tau prion replication in vivo. Our findings
      provide evidence for selective vulnerability in mice resulting in highly
      regulated levels of tau prion propagation, thus affording a model for
      identification of additional molecules that could mitigate the levels of tau
      prions in human tauopathies.

PMID- 29203674
TI  - Structural insights into the roles of the IcmS-IcmW complex in the type IVb
      secretion system of Legionella pneumophila.
AB  - The type IVb secretion system (T4BSS) of Legionella pneumophila is a multiple
      component apparatus that delivers ~300 virulent effector proteins into host
      cells. The injected effectors modulate host cellular processes to promote
      bacterial infection and proliferation. IcmS and IcmW are two conserved small,
      acidic adaptor proteins that form a binary complex to interact with many
      effectors and facilitate their translocation. IcmS and IcmW can also interact
      with DotL, an ATPase of the type IV coupling protein complex (T4CP). However, how
      IcmS-IcmW recognizes effectors, and what the roles of IcmS-IcmW are in T4BSSs are
      unclear. In this study, we found that IcmS and IcmW form a 1:1 heterodimeric
      complex to bind effector substrates. Both IcmS and IcmW adopt new structural
      folds and have no structural similarities with known effector chaperones. IcmS
      has a compact global structure with an alpha/beta fold, while IcmW adopts a fully
      alpha-folded, relatively loose architecture. IcmS stabilizes IcmW by binding to
      its two C-terminal alpha-helices. Photocrosslinking assays revealed that the IcmS
      IcmW complex binds its cognate effectors via an extended hydrophobic surface,
      which can also interact with the C terminus of DotL. A crystal structure of the
      DotL-IcmS-IcmW complex reveals extensive and highly stable interactions between
      DotL and IcmS-IcmW. Moreover, IcmS-IcmW recruits LvgA to DotL and assembles a
      unique T4CP. These data suggest that IcmS-IcmW also functions as an inseparable
      integral component of the DotL-T4CP complex in the bacterial inner membrane. This
      study provides molecular insights into the dual roles of the IcmS-IcmW complex in
      T4BSSs.

PMID- 29203675
TI  - Extending density functional embedding theory for covalently bonded systems.
AB  - Quantum embedding theory aims to provide an efficient solution to obtain accurate
      electronic energies for systems too large for full-scale, high-level quantum
      calculations. It adopts a hierarchical approach that divides the total system
      into a small embedded region and a larger environment, using different levels of
      theory to describe each part. Previously, we developed a density-based quantum
      embedding theory called density functional embedding theory (DFET), which
      achieved considerable success in metals and semiconductors. In this work, we
      extend DFET into a density-matrix-based nonlocal form, enabling DFET to study the
      stronger quantum couplings between covalently bonded subsystems. We name this
      theory density-matrix functional embedding theory (DMFET), and we demonstrate its
      performance in several test examples that resemble various real applications in
      both chemistry and biochemistry. DMFET gives excellent results in all cases
      tested thus far, including predicting isomerization energies, proton transfer
      energies, and highest occupied molecular orbital-lowest unoccupied molecular
      orbital gaps for local chromophores. Here, we show that DMFET systematically
      improves the quality of the results compared with the widely used state-of-the
      art methods, such as the simple capped cluster model or the widely used ONIOM
      method.

PMID- 29203676
TI  - STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm
      migration in the mouse embryo.
AB  - Regulated mesoderm migration is necessary for the proper morphogenesis and organ
      formation during embryonic development. Cell migration and its dependence on the
      cytoskeleton and signaling machines have been studied extensively in cultured
      cells; in contrast, remarkably little is known about the mechanisms that regulate
      mesoderm cell migration in vivo. Here, we report the identification and
      characterization of a mouse mutation in striatin-interacting protein 1 (Strip1)
      that disrupts migration of the mesoderm after the gastrulation epithelial-to
      mesenchymal transition (EMT). STRIP1 is a core component of the biochemically
      defined mammalian striatin-interacting phosphatases and kinase (STRIPAK)
      complexes that appear to act through regulation of protein phosphatase 2A (PP2A),
      but their functions in mammals in vivo have not been examined. Strip1-null
      mutants arrest development at midgestation with profound disruptions in the
      organization of the mesoderm and its derivatives, including a complete failure of
      the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants
      and mouse embryonic fibroblasts from null mutants shows that the mesoderm
      migration defect is correlated with decreased cell spreading, abnormal focal
      adhesions, changes in the organization of the actin cytoskeleton, and decreased
      velocity of cell migration. The results show that STRIPAK complexes are essential
      for cell migration and tissue morphogenesis in vivo.

PMID- 29203677
TI  - Dynamics of translation can determine the spatial organization of membrane-bound
      proteins and their mRNA.
AB  - Unlike most macromolecules that are homogeneously distributed in the bacterial
      cell, mRNAs that encode inner-membrane proteins can be concentrated near the
      inner membrane. Cotranslational insertion of the nascent peptide into the
      membrane brings the translating ribosome and the mRNA close to the membrane. This
      suggests that kinetic properties of translation can determine the spatial
      organization of these mRNAs and proteins, which can be modulated through
      posttranscriptional regulation. Here we use a simple stochastic model of
      translation to characterize the effect of mRNA properties on the dynamics and
      statistics of its spatial distribution. We show that a combination of the rate of
      translation initiation, the availability of secretory apparatuses, and the
      composition of the coding region determines the abundance of mRNAs near the
      membrane, as well as their residence time. We propose that the spatiotemporal
      dynamics of mRNAs can give rise to protein clusters on the membrane and determine
      their size distribution.

PMID- 29203678
TI  - Multiple oscillatory rhythms determine the temporal organization of perception.
AB  - Incoming sensory input is condensed by our perceptual system to optimally
      represent and store information. In the temporal domain, this process has been
      described in terms of temporal windows (TWs) of integration/segregation, in which
      the phase of ongoing neural oscillations determines whether two stimuli are
      integrated into a single percept or segregated into separate events. However, TWs
      can vary substantially, raising the question of whether different TWs map onto
      unique oscillations or, rather, reflect a single, general fluctuation in cortical
      excitability (e.g., in the alpha band). We used multivariate decoding of
      electroencephalography (EEG) data to investigate perception of stimuli that
      either repeated in the same location (two-flash fusion) or moved in space
      (apparent motion). By manipulating the interstimulus interval (ISI), we created
      bistable stimuli that caused subjects to perceive either integration
      (fusion/apparent motion) or segregation (two unrelated flashes). Training a
      classifier searchlight on the whole channels/frequencies/times space, we found
      that the perceptual outcome (integration vs. segregation) could be reliably
      decoded from the phase of prestimulus oscillations in right parieto-occipital
      channels. The highest decoding accuracy for the two-flash fusion task (ISI = 40
      ms) was evident in the phase of alpha oscillations (8-10 Hz), while the highest
      decoding accuracy for the apparent motion task (ISI = 120 ms) was evident in the
      phase of theta oscillations (6-7 Hz). These results reveal a precise relationship
      between specific TW durations and specific oscillations. Such oscillations at
      different frequencies may provide a hierarchical framework for the temporal
      organization of perception.

PMID- 29203679
TI  - Naturalization of European plants on other continents: The role of donor
      habitats.
AB  - The success of European plant species as aliens worldwide is thought to reflect
      their association with human-disturbed environments. However, an explicit test
      including all human-made, seminatural and natural habitat types of Europe, and
      their contributions as donor habitats of naturalized species to the rest of the
      globe, has been missing. Here we combine two databases, the European Vegetation
      Checklist and the Global Naturalized Alien Flora, to assess how human influence
      in European habitats affects the probability of naturalization of their plant
      species on other continents. A total of 9,875 native European vascular plant
      species were assigned to 39 European habitat types; of these, 2,550 species have
      become naturalized somewhere in the world. Species that occur in both human-made
      habitats and seminatural or natural habitats in Europe have the highest
      probability of naturalization (64.7% and 64.5% of them have naturalized). Species
      associated only with human-made or seminatural habitats still have a
      significantly higher probability of becoming naturalized (41.7% and 28.6%,
      respectively) than species confined to natural habitats (19.4%). Species
      associated with arable land and human settlements were recorded as naturalized in
      the largest number of regions worldwide. Our findings highlight that plant
      species' association with native-range habitats disturbed by human activities,
      combined with broad habitat range, play an important role in shaping global
      patterns of plant invasions.

PMID- 29203680
TI  - Developing a written action plan for children with eczema: a qualitative study.
AB  - BACKGROUND: Eczema is common in children but adherence to treatments is poor.
      Written action plans (WAPs) have been shown to help in asthma but the potential
      value, format, and content of an eczema WAP is unknown. AIM: To explore the
      potential role of an eczema WAP, and to design an eczema-specific WAP. DESIGN AND
      SETTING: A qualitative study of parents of children with eczema, primary and
      secondary care health professionals, and other stakeholders. METHOD: A total of
      41 semi-structured one-to-one interviews and two focus groups were audiorecorded,
      transcribed, and analysed thematically. RESULTS: Reported challenges of managing
      eczema included: parental confusion about treatment application; lack of verbal
      and written advice from GPs; differing beliefs about the cause and management of
      eczema; re-prescribing of failed treatments; and parents feeling unsupported by
      their GP. An eczema WAP was viewed as an educational tool that could help address
      these problems. Participants expressed a preference for a WAP that gives clear,
      individualised guidance on treatment use, presented in a step-up/step-down
      approach. Participants also wanted more general information about eczema, its
      potential triggers, and how to manage problem symptoms. CONCLUSION: An eczema WAP
      may help overcome some of the difficulties of managing eczema, and support
      families and clinicians in the management of the condition. Further evaluation is
      needed to determine if the eczema WAP the authors have developed is both
      acceptable and improves the outcomes for affected children and their families.

PMID- 29203681
TI  - Patients' views on interactions with practitioners for type 2 diabetes: a
      longitudinal qualitative study in primary care over 10 years.
AB  - BACKGROUND: It has been suggested that interactions between patients and
      practitioners in primary care have the potential to delay progression of
      complications in type 2 diabetes. However, as primary care faces greater
      pressures, patient experiences of patient-practitioner interactions might be
      changing. AIM: To explore the views of patients with type 2 diabetes on factors
      that are of significance to them in patient-practitioner interactions in primary
      care after diagnosis, and over the last 10 years of living with the disease.
      DESIGN AND SETTING: A longitudinal qualitative analysis over 10 years in UK
      primary care. METHOD: The study was part of a qualitative and quantitative
      examination of patient experience within the existing ADDITION-Cambridge and
      ADDITION-Plus trials from 2002 to 2016. The researchers conducted a qualitative
      descriptive analysis of free-text comments to an open-ended question within the
      CARE measure questionnaire at 1 and 10 years after diagnosis with diabetes. Data
      were analysed cross-sectionally at each time point, and at an individual level
      moving both backwards and forwards between time points to describe emergent
      topics. RESULTS: At the 1-year follow-up, 311 out of 1106 (28%) participants had
      commented; 101 out of 380 (27%) participants commented at 10-year follow-up; and
      46 participants commented at both times. Comments on preferences for face-to-face
      contact, more time with practitioners, and relational continuity of care were
      more common over time. CONCLUSION: This study highlights issues related to the
      wider context of interactions between patients and practitioners in the
      healthcare system over the last 10 years since diagnosis. Paradoxically, these
      same aspects of care that are valued over time from diagnosis are also
      increasingly unprotected in UK primary care.

PMID- 29203682
TI  - Reasons why people do not attend NHS Health Checks: a systematic review and
      qualitative synthesis.
AB  - BACKGROUND: The NHS Health Check programme is a prevention initiative offering
      cardiovascular risk assessment and management advice to adults aged 40-74 years
      across England. Its effectiveness depends on uptake. When it was introduced in
      2009, it was anticipated that all those eligible would be invited over a 5-year
      cycle and 75% of those invited would attend. So far in the current cycle from
      2013 to 2018, 33.8% of those eligible have attended, which is equal to 48.5% of
      those invited to attend. Understanding the reasons why some people do not attend
      is important to maximise the impact of the programmes. AIM: To review why people
      do not attend NHS Health Checks. DESIGN AND SETTING: A systematic review and
      thematic synthesis of qualitative studies. METHOD: An electronic literature
      search was carried out of MEDLINE, Embase, Health Management Information
      Consortium, Cumulative Index to Nursing and Allied Health Literature, Global
      Health, PsycINFO, Web of Science, OpenGrey, the Cochrane Library, NHS Evidence,
      Google Scholar, Google, ClinicalTrials.gov, and the ISRCTN registry from 1
      January 1996 to 9 November 2016, and the reference lists of all included papers
      were also screened manually. Inclusion criteria were primary research studies
      that reported the views of people who were eligible for but had not attended an
      NHS Health Check. RESULTS: Nine studies met the inclusion criteria. Reasons for
      not attending included lack of awareness or knowledge, misunderstanding the
      purpose of the NHS Health Check, aversion to preventive medicine, time
      constraints, difficulties with access to general practices, and doubts regarding
      pharmacies as appropriate settings. CONCLUSION: The findings particularly
      highlight the need for improved communication and publicity around the purpose of
      the NHS Health Check programme and the personal health benefits of risk factor
      detection.

PMID- 29203683
TI  - Possible missed opportunities for diagnosing colorectal cancer in Dutch primary
      care: a multimethods approach.
AB  - BACKGROUND: Early detection of colorectal cancer (CRC) is important to achieve
      better survival. Discriminating symptoms suggestive of CRC from benign conditions
      is a challenge for GPs because most known 'alarm symptoms' have low predictive
      values. AIM: To further understand the diagnostic process of CRC in general
      practice in terms of healthcare use and by analysing factors related to
      diagnostic intervals. DESIGN AND SETTING: A multimethod approach comprising a
      historical, prospective registry study and qualitative content analysis. METHOD:
      Healthcare use in the year before referral for colonoscopy was compared between
      patients diagnosed with CRC and an age-, sex,- and GP-matched control population.
      Qualitative content analysis was performed on free texts in electronic patient
      records from a purposive sample of patients with CRC. RESULTS: Patients with CRC
      (n = 287) had 41% (25-59%) more face-to-face contacts and 21% (7-37%) more
      medication prescriptions than controls (n = 828). Forty-six per cent of patients
      with CRC had two or more contacts for digestive reasons, compared with 12.2% of
      controls, more often for symptoms than diagnoses. From qualitative analysis two
      themes emerged: 'possible missed diagnostic opportunities' and 'improvements in
      diagnostic process unlikely'. Possible missed diagnostic opportunities were
      related to patients waiting before presenting symptoms, doctors attributing
      symptoms to comorbid conditions or medication use, or doctors sticking to an
      initial diagnosis. CONCLUSION: Fewer missed diagnostic opportunities might occur
      if GPs are aware of pitfalls in diagnosing CRC: the assumption that symptoms are
      caused by comorbid conditions or medication, or relating complaints to pre
      existing medical conditions. GPs also need to be aware that repeated digestive
      complaints warrant rethinking an earlier diagnosis.

PMID- 29203684
TI  - Nonpharmacological Management of Atrial Fibrillation in Patients at High
      Intracranial Hemorrhage Risk.

PMID- 29203685
TI  - Cerebral Venous Thrombosis in Older Patients.
AB  - BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is rare in older
      patients. We investigated whether clinical features and outcomes differ in older
      and younger patients. METHODS: We used data from a multicenter observational
      registry of consecutive adult patients with CVT admitted between 1987 and 2016.
      We compared demographics, clinical manifestations, and outcomes between older
      (upper quartile of the age distribution) and younger (lower 3 quartiles of the
      age distribution) patients. RESULTS: Data for 843 patients with CVT were
      available. The median age was 43 years (interquartile range, 30-55 years). Older
      patients (>=55 years; n=222) were less often women than younger patients (48%
      versus 71%; P<0.001) and less often reported headache (63% versus 87%; P<0.001).
      Cancer was more common in older patients (24% versus 9%; P<0.001), especially
      solid malignancies (19% versus 5%; P<0.001). Outcome at follow-up was worse in
      older patients (modified Rankin Scale, 3-6; adjusted odds ratio, 2.68; 95%
      confidence interval, 1.78-4.03; mortality, adjusted odds ratio, 2.13; 95%
      confidence interval, 1.09-4.19). CONCLUSIONS: The sex ratio of CVT is evenly
      distributed in older patients, probably because of the dissipation of hormonal
      influences. Malignancy should be considered as a potential precipitant in older
      patients with CVT.

PMID- 29203687
TI  - How Nurses Can Partner With National Institutes of Health StrokeNet to Deliver
      Best Research and Care to Stroke Patients.

PMID- 29203686
TI  - Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major
      Vascular Events.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate whether pulse pressure
      (PP) obtained during the acute stage of ischemic stroke can be used as a
      predictor for future major vascular events. METHODS: Using a multicenter
      prospective stroke registry database, patients who were hospitalized for ischemic
      stroke within 48 hours of onset were enrolled in this study. We analyzed blood
      pressure (BP) data measured during the first 3 days from onset. Primary and
      secondary outcomes were time to a composite of stroke recurrence, myocardial
      infarction, all-cause death, and time to stroke recurrence, respectively.
      RESULTS: Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial
      infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional
      hazards models including both linear and quadratic terms of PP, PP had a
      nonlinear J-shaped relationship with primary (for a quadratic term of PP,
      P=0.004) and secondary (P<0.001) outcomes. The overall effects of PP and other BP
      parameters on primary and secondary outcomes were also significant (P<0.05). When
      predictive power of BP parameters was compared using a statistic of -2 log
      likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus
      5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56),
      and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and
      secondary outcomes, respectively. CONCLUSIONS: Our study shows that PP when
      measured in the acute period of ischemic stroke has nonlinear J-shaped
      relationships with major vascular events and stroke recurrence, and may have a
      stronger predictive power than other commonly used BP parameters.

PMID- 29203688
TI  - Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm
      Rupture.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested a protective effect of
      diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports
      are inconsistent, and objective measures of hyperglycemia in these studies are
      lacking. Our aim was to investigate the association between aneurysmal
      subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin
      levels. METHODS: The medical records of 4701 patients with 6411 intracranial
      aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts
      General Hospital and Brigham and Women's Hospital between 1990 and 2016 were
      reviewed and analyzed. Patients were separated into ruptured and nonruptured
      groups. Univariate and multivariate logistic regression analyses were performed
      to determine the association between aneurysmal subarachnoid hemorrhage and
      antihyperglycemic agents and glycated hemoglobin levels. Propensity score
      weighting was used to account for selection bias. RESULTS: In both unweighted and
      weighted multivariate analysis, antihyperglycemic agent use was inversely and
      significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58;
      95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence
      interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not
      significantly associated with rupture status. CONCLUSIONS: Antihyperglycemic
      agent use rather than hyperglycemia is associated with decreased risk of
      aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of
      glucose-lowering agents in the pathogenesis of aneurysm rupture.

PMID- 29203689
TI  - Novel Interactive Data Visualization: Exploration of the ESCAPE Trial
      (Endovascular Treatment for Small Core and Anterior Circulation Proximal
      Occlusion With Emphasis on Minimizing CT to Recanalization Times) Data.
AB  - BACKGROUND AND PURPOSE: The ESCAPE (Endovascular Treatment for Small Core and
      Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to
      Recanalization Times) randomized clinical trial collected a large diverse data
      set. However, it is difficult to fully understand the effects of the study on
      certain patient groups and disease progression. We developed and evaluated an
      interactive visualization of the ESCAPE trial data. METHODS: We iteratively
      designed an interactive visualization using Python's Bokeh software library. The
      design was evaluated through a user study, which quantitatively evaluated its
      efficiency and accuracy against traditional modified Rankin Scalegraphic.
      Qualitative feedback was also evaluated. RESULTS: The novel interactive
      visualization of the ESCAPE data are publicly available at
      http://escapevisualization.herokuapp.com/. There was no difference in the
      efficiency and accuracy when comparing the use of the novel with the traditional
      visualization. However, users preferred the novel visualization because it
      allowed for greater exploration. Some insights obtained through exploration of
      the ESCAPE data are presented. CONCLUSIONS: Novel interactive visualizations can
      be applied to acute stroke trial data to allow for greater exploration of the
      results. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01778335.

PMID- 29203690
TI  - Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A
      Prospective Observational Study.
AB  - BACKGROUND AND PURPOSE: Central autonomic dysfunction increases stroke morbidity
      and mortality. We aimed to investigate whether poststroke autonomic dysfunction
      graded by Ewing battery can predict clinical outcome. METHODS: In this
      prospective observational study, we assessed autonomic function of ischemic
      stroke patients within 7 days from symptom onset by Ewing battery. On the basis
      of the magnitude of autonomic dysfunction, we stratified patients into
      significant (definite, severe, or atypical) or minor (normal or early) autonomic
      function impairment groups and correlated the impairment with the 3-month
      modified Rankin Scale score (good outcome: modified Rankin Scale score 0~2; poor
      outcome: modified Rankin Scale score 3~6). RESULTS: Among the 150 patients
      enrolled (mean age, 66.4+/-9.9 years; 70.7% males), minor autonomic dysfunction
      was identified in 36 patients (24.0%), and significant autonomic dysfunction was
      identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor
      functional outcome was found in 32.5% of significant group patients compared with
      13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of
      autonomic dysfunction and 3-month unfavorable functional outcome after acute
      ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P=0.036). After
      adjusting for confounding variables with statistical significance between the 2
      functional outcome subgroups identified in univariate analysis (including sex and
      National Institutes of Health Stroke Scale score on admission), the magnitude of
      autonomic dysfunction still independently predicted an unfavorable outcome, with
      an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P=0.027).
      CONCLUSIONS: Autonomic dysfunction gauged by Ewing battery predicts poor
      functional outcome after acute ischemic stroke.

PMID- 29203693
TI  - Precision Medicine: Progress, Pitfalls, and Promises.

PMID- 29203694
TI  - Path toward Precision Oncology: Review of Targeted Therapy Studies and Tools to
      Aid in Defining "Actionability" of a Molecular Lesion and Patient Management
      Support.
AB  - Precision medicine trials and targeted therapies have shifted to the forefront of
      oncology. Although targeted therapies have shown initial promise, implementation
      across the broad landscape of oncology has many challenges. These limitations
      include an incomplete understanding of the functional significance of variant
      alleles as well as the need for clinical research and practice models that are
      more patient-centered and account for the complexity of individual patient
      tumors. Furthermore, successful implementation of targeted therapies will also be
      predicated on efforts to standardize the framework for patient management
      support. Here, we review current implementations of targeted therapies in
      precision oncology and discuss how "actionability" is defined for molecular
      targets in cancer therapeutics. We also comment on the growing need for
      bioinformatics tools and data platforms to complement advances in precision
      oncology. Finally, we discuss current frameworks for integrating precision
      oncology into patient management and propose an integrated model that combines
      features of molecular tumor boards and decision support systems. Mol Cancer Ther;
      16(12); 2645-55. (c)2017 AACRSee related article by Pilie et al., p. 2641.

PMID- 29203695
TI  - Random Factors: An Interview with 2017 Thomas Hunt Morgan Medal Recipient Richard
      C. Lewontin.
AB  - The Thomas Hunt Morgan Medal is awarded to an individual member of the Genetics
      Society of America for lifetime achievement in the field of genetics. It
      recognizes the full body of work of an exceptional geneticist. The 2017 recipient
      is Richard C. Lewontin, whose contributions and influence have profoundly shaped
      the field of evolutionary genetics. As a testament to this legacy, his nomination
      for the Morgan Medal was cosigned by 160 faculty members from around the world. A
      student of Theodosius Dobzhansky, Lewontin's early work established the two-locus
      theory, which laid the foundation for our understanding of linkage
      disequilibrium. In the 1960s, he collaborated with biochemist Jack Hubby on a
      method to quantify natural genetic variation using protein gel electrophoresis.
      This approach helped launch the field of molecular evolution and spurred a great
      influx of data into a formerly theory-dominated domain. The subsequent
      contributions of Lewontin and his group helped set the stage for much of modern
      population genetics and genomics research. As well as this direct impact,
      Lewontin influenced the field through his guidance and inspiration, as well as
      through his capacity to spur vigorous but productive debates. His prominent role
      as a writer and social commentator included highlighting problems with the
      inference of heritability, concepts of race, and the overemphasis of genetic
      influences on phenotypes.

PMID- 29203696
TI  - Treasure Your Exceptions: An Interview with 2017 George Beadle Award Recipient
      Susan A. Gerbi.
AB  - THE Genetics Society of America's (GSA) George W. Beadle Award honors individuals
      who have made outstanding contributions to the community of genetics researchers
      and who exemplify the qualities of its namesake. The 2017 recipient is Susan A.
      Gerbi, who has been a prominent leader and advocate for the scientific community.
      In the course of her research on DNA replication, Gerbi helped develop the method
      of Replication Initiation Point (RIP) mapping to map replication origins at the
      nucleotide level, improving resolution by two orders of magnitude. RIP mapping
      also provides the basis for the now popular use of lambda-exonuclease to enrich
      nascent DNA to map replication origins genome-wide. Gerbi's second area of
      research on ribosomal RNA revealed a conserved core secondary structure, as well
      as conserved nucleotide elements (CNEs). Some CNEs are universally conserved,
      while other CNEs are conserved in all eukaryotes but not in archaea or bacteria,
      suggesting a eukaryotic function. Intriguingly, the majority of the eukaryotic
      specific CNEs line the tunnel of the large ribosomal subunit through which the
      nascent polypeptide exits. Gerbi has promoted the fly Sciara coprophila as a
      model organism ever since she used its enormous polytene chromosomes to help
      develop the method of in situ hybridization during her Ph.D. research in Joe
      Gall's laboratory. The Gerbi laboratory maintains the Sciara International Stock
      Center and manages its future, actively spreading Sciara stocks to other
      laboratories. Gerbi has also served in many leadership roles, working on issues
      of science policy, women in science, scientific training, and career preparation.
      This is an abridged version of the interview. The full interview is available on
      the Genes to Genomes blog, at genestogenomes.org/gerbi.

PMID- 29203697
TI  - Frontiers of Knowledge: An Interview with 2017 Edward Novitski Prize Recipient
      Jonathan Hodgkin.
AB  - The Genetics Society of America's Edward Novitski Prize recognizes a single
      experimental accomplishment or a body of work in which an exceptional level of
      creativity and intellectual ingenuity has been used to design and execute
      scientific experiments to solve a difficult problem in genetics. The 2017 winner,
      Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination
      pathway in Caenorhabditis elegans He inferred the order of genes in the pathway
      and their modes of regulation using epistasis analyses-a powerful tool that was
      quickly adopted by other researchers. He expanded the number and use of
      informational suppressor mutants in C. elegans that are able to act on many
      genes. He also introduced the use of collections of wild C. elegans to study
      naturally occurring genetic variation, paving the way for SNP mapping and QTL
      analysis, as well as studies of hybrid incompatibilities between worm species.
      His current work focuses on nematode-bacterial interactions and innate immunity.

PMID- 29203698
TI  - Beautiful Piles of Bones: An Interview with 2017 Genetics Society of America
      Medal Recipient David M. Kingsley.
AB  - The Genetics Society of America Medal is awarded to an individual for outstanding
      contributions to the field of genetics in the last 15 years. Recipients of the
      GSA Medal are recognized for elegant and highly meaningful contributions to
      modern genetics, exemplifying the ingenuity of GSA membership. The 2017 recipient
      is David M. Kingsley, whose work in mouse, sticklebacks, and humans has shifted
      paradigms about how vertebrates evolve. Kingsley first fell in love with genetics
      in graduate school, where he worked on receptor mediated endocytosis with Monty
      Krieger. In his postdoctoral training he was able to unite genetics with his
      first scientific love: vertebrate morphology. He joined the group of Neal
      Copeland and Nancy Jenkins, where he led efforts to map the classical mouse
      skeletal mutation short ear Convinced that experimental genetics had a unique
      power to reveal the inner workings of evolution, Kingsley then established the
      stickleback fish as an extraordinarily productive model of quantitative trait
      evolution in wild species. He and his colleagues revealed many important
      insights, including the discoveries that major morphological differences can map
      to key loci with large effects, that regulatory changes in essential
      developmental control genes have produced advantageous new traits, and that
      nature has selected the same genes over and over again to drive the stickleback's
      skeletal evolution. Recently, Kingsley's group has been using these lessons to
      reveal more about how our own species evolved.This is an abridged version of the
      interview. The full interview is available on the Genes to Genomes blog, at
      genestogenomes.org/kingsley/.

PMID- 29203700
TI  - Previous Recipients of GSA Awards.

PMID- 29203699
TI  - Inside the Literature: An Interview with Sally G. Hoskins, 2017 Recipient of the
      Elizabeth W. Jones Award for Excellence in Education.
AB  - The Genetics Society of America's Elizabeth W. Jones Award for Excellence in
      Education recognizes significant and sustained impact on genetics education. The
      2017 recipient is Sally G. Hoskins, in recognition of her role in developing and
      promoting the transformative science education method CREATE (Consider, Read,
      Elucidate hypotheses, Analyze and interpret data, and Think of the next
      Experiment). This innovative approach uses primary literature to engage students,
      allowing them to experience for themselves the creativity and challenge of study
      design, analysis, interpretation, collaboration, and debate. Comprehensive
      evaluation of CREATE has consistently found that students improve in difficult-to
      teach skills like critical thinking and experimental design, while showing
      improved attitudes and beliefs about science.This is an abridged version of the
      interview. The full interview is available on the Genes to Genomes blog, at
      genestogenomes.org/hoskins/.

PMID- 29203703
TI  - Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.

PMID- 29203702
TI  - Gene Tagging Strategies To Assess Protein Expression, Localization, and Function
      in Drosophila.

PMID- 29203701
TI  - Regulation of Carbohydrate Energy Metabolism in Drosophila melanogaster.
AB  - Carbohydrate metabolism is essential for cellular energy balance as well as for
      the biosynthesis of new cellular building blocks. As animal nutrient intake
      displays temporal fluctuations and each cell type within the animal possesses
      specific metabolic needs, elaborate regulatory systems are needed to coordinate
      carbohydrate metabolism in time and space. Carbohydrate metabolism is regulated
      locally through gene regulatory networks and signaling pathways, which receive
      inputs from nutrient sensors as well as other pathways, such as developmental
      signals. Superimposed on cell-intrinsic control, hormonal signaling mediates
      intertissue information to maintain organismal homeostasis. Misregulation of
      carbohydrate metabolism is causative for many human diseases, such as diabetes
      and cancer. Recent work in Drosophila melanogaster has uncovered new regulators
      of carbohydrate metabolism and introduced novel physiological roles for
      previously known pathways. Moreover, genetically tractable Drosophila models to
      study carbohydrate metabolism-related human diseases have provided new insight
      into the mechanisms of pathogenesis. Due to the high degree of conservation of
      relevant regulatory pathways, as well as vast possibilities for the analysis of
      gene-nutrient interactions and tissue-specific gene function, Drosophila is
      emerging as an important model system for research on carbohydrate metabolism.

PMID- 29203706
TI  - Heat shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective.
AB  - Many heat shock proteins (HSPs) are essential to survival as a consequence of
      their role as molecular chaperones, and play a critical role in maintaining
      cellular proteostasis by integrating the fundamental processes of protein folding
      and degradation. HSPs are arguably among the most prominent classes of proteins
      that have been broadly linked to many human disorders, with changes in their
      expression profile and/or intracellular/extracellular location now being
      described as contributing to the pathogenesis of a number of different diseases.
      Although the concept was initially controversial, it is now widely accepted that
      HSPs have additional biological functions over and above their role in
      proteostasis (so-called 'protein moonlighting'). Most importantly, these new
      insights are enlightening our understanding of biological processes in health and
      disease, and revealing novel and exciting therapeutic opportunities. This theme
      issue draws on therapeutic insights from established research on HSPs in cancer
      and other non-communicable disorders, with an emphasis on how the intracellular
      function of HSPs contrasts with their extracellular properties and function, and
      interrogates their potential diagnostic and therapeutic value to the prevention,
      management and treatment of chronic diseases.This article is part of the theme
      issue 'Heat shock proteins as modulators and therapeutic targets of chronic
      disease: an integrated perspective'.

PMID- 29203707
TI  - Extracellular cell stress (heat shock) proteins-immune responses and disease: an
      overview.
AB  - Extracellular cell stress proteins are highly conserved phylogenetically and have
      been shown to act as powerful signalling agonists and receptors for selected
      ligands in several different settings. They also act as immunostimulatory 'danger
      signals' for the innate and adaptive immune systems. Other studies have shown
      that cell stress proteins and the induction of immune reactivity to self-cell
      stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60,
      Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties,
      depending on the context in which they encounter responding immune cells. The
      burgeoning literature reporting the presence of stress proteins in a range of
      biological fluids in healthy individuals/non-diseased settings, the association
      of extracellular stress protein levels with a plethora of clinical and
      pathological conditions and the selective expression of a membrane form of Hsp70
      on cancer cells now supports the concept that extracellular cell stress proteins
      are involved in maintaining/regulating organismal homeostasis and in disease
      processes and phenotype. Cell stress proteins, therefore, form a biologically
      complex extracellular cell stress protein network having diverse biological,
      homeostatic and immunomodulatory properties, the understanding of which offers
      exciting opportunities for delivering novel approaches to predict, identify,
      diagnose, manage and treat disease.This article is part of the theme issue 'Heat
      shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203708
TI  - Protein moonlighting: what is it, and why is it important?
AB  - Members of the GroEL/HSP60 protein family have been studied for many years
      because of their critical roles as ATP-dependent molecular chaperones, so it
      might come as a surprise that some have important functions in ATP-poor
      conditions, for example, when secreted outside the cell. At least some members of
      each of the HSP10, HSP70, HSP90, HSP100 and HSP110 heat shock protein families
      are also 'moonlighting proteins'. Moonlighting proteins exhibit more than one
      physiologically relevant biochemical or biophysical function within one
      polypeptide chain. In this class of multifunctional proteins, the multiple
      functions are not due to gene fusions or multiple proteolytic fragments. Several
      hundred moonlighting proteins have been identified, and they include a diverse
      set of proteins with a large variety of functions. Some participate in multiple
      biochemical processes by using an active site pocket for catalysis and a
      different part of the protein's surface to interact with other proteins.
      Moonlighting proteins play a central role in many diseases, and the development
      of novel treatments would be aided by more information addressing current
      questions, for example, how some are targeted to multiple cellular locations and
      how a single function can be targeted by therapeutics without targeting a
      function not involved in disease.This article is part of the theme issue 'Heat
      shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203709
TI  - Heat shock proteins and cancer: intracellular chaperones or extracellular
      signalling ligands?
AB  - Heat shock proteins (HSPs) are found at elevated concentrations in tumour cells,
      and this increase reflects the proteotoxic stress experienced by the cells due to
      expanding levels of the mutated oncoproteins that drive tumorigenesis. The
      protection of oncogenic proteins by HSPs offers a window of vulnerability in
      tumour metabolism that has been exploited using Hsp90-targeting drugs. Such
      compounds have been shown to cause inhibition and degradation of a wide range of
      proteins essential for oncogenesis. Recently, Hsp90 has also been shown to be
      secreted by tumour cells and to interact in autocrine or paracrine manners with
      the surfaces of adjacent cells, leading to increased growth and metastasis.
      Future studies will address a number of key questions associated with these
      findings, including the relative importance of intracellular versus extracellular
      HSPs in tumorigenesis, as well as overcoming potential problems with normal
      tissue toxicity associated with Hsp90 drugs. Targeting individual members of HSP
      families and inactivating extracellular HSPs may be desirable future approaches
      that offer increased selectivity in targeting HSPs in cancer.This article is part
      of the theme issue 'Heat shock proteins as modulators and therapeutic targets of
      chronic disease: an integrated perspective'.

PMID- 29203710
TI  - The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from
      proteomic stability to oncogenesis.
AB  - The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is
      characterized by induction of heat-shock proteins (HSPs). As molecular
      chaperones, HSPs facilitate the folding, assembly, transportation and degradation
      of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator
      of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR
      is essential to proteome homeostasis, or proteostasis, thereby resisting stress
      and antagonizing protein misfolding diseases and ageing. Contrasting with these
      benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas
      HSF1 remains latent in primary cells without stress, it becomes constitutively
      activated within malignant cells, rendering them addicted to HSF1 for their
      growth and survival. Highlighting the HSR/HPSR as an integral component of the
      oncogenic network, several key pathways governing HSF1 activation by
      environmental stressors are causally implicated in malignancy. Importantly, HSF1
      impacts the cancer proteome systemically. By suppressing tumour-suppressive
      amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant
      state, both providing insight into how HSF1 enables tumorigenesis and suggesting
      disruption of cancer proteostasis as a therapeutic strategy. This review provides
      an overview of the role of HSF1 in oncogenesis, mechanisms underlying its
      constitutive activation within cancer cells and its pro-oncogenic action, as well
      as potential HSF1-targeting strategies.This article is part of the theme issue
      'Heat shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203712
TI  - Heat shock protein 90: its inhibition and function.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable
      protein maturation, stabilization of aggregation-prone proteins, quality control
      of misfolded proteins and assists in keeping proteins in activation-competent
      conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90
      utilizing a co-chaperone-assisted cycle. Co-chaperones play a role in client
      transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90
      conformational states. Many of the proteins chaperoned by Hsp90 (Hsp90 clients)
      are essential for the progression of various diseases, including cancer,
      Alzheimer's disease and other neurodegenerative diseases, as well as viral and
      bacterial infections. Given the importance of these clients in different diseases
      and their dynamic interplay with the chaperone machinery, it has been suggested
      that targeting Hsp90 and its respective co-chaperones may be an effective method
      for combating a large range of illnesses.This article is part of the theme issue
      'Heat shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203711
TI  - Membrane heat shock protein 70: a theranostic target for cancer therapy.
AB  - Members of the 70 kDa stress protein family are found in nearly all subcellular
      compartments of nucleated cells where they fulfil a number of chaperoning
      functions. Heat shock protein 70 (HSP70), also termed HSPA1A, the major stress
      inducible member of this family is overexpressed in a large variety of different
      tumour types. Apart from its intracellular localization, a tumour-selective HSP70
      membrane expression has been determined. A membrane HSP70-positive tumour
      phenotype is associated with aggressiveness and therapy resistance, but also
      serves as a recognition structure for targeted therapies. Furthermore, membrane
      bound and extracellularly residing HSP70 derived from tumour cells play pivotal
      roles in eliciting anti-tumour immune responses. Herein, we want to shed light on
      the multiplicity of different activities of HSP70, depending on its
      intracellular, membrane and extracellular localization with the goal to use
      membrane HSP70 as a target for novel therapies including nanoparticle-based
      approaches for the treatment of cancer.This article is part of the theme issue
      'Heat shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203713
TI  - Therapeutic potential of heat shock protein induction for muscular dystrophy and
      other muscle wasting conditions.
AB  - Duchenne muscular dystrophy is the most common and severe of the muscular
      dystrophies, a group of inherited myopathies caused by different genetic
      mutations leading to aberrant expression or complete absence of cytoskeletal
      proteins. Dystrophic muscles are prone to injury, and regenerate poorly after
      damage. Remorseless cycles of muscle fibre breakdown and incomplete repair lead
      to progressive and severe muscle wasting, weakness and premature death. Many
      other conditions are similarly characterized by muscle wasting, including
      sarcopenia, cancer cachexia, sepsis, denervation, burns, and chronic obstructive
      pulmonary disease. Muscle trauma and loss of mass and physical capacity can
      significantly compromise quality of life for patients. Exercise and nutritional
      interventions are unlikely to halt or reverse the conditions, and strategies
      promoting muscle anabolism have limited clinical acceptance. Heat shock proteins
      (HSPs) are molecular chaperones that help proteins fold back to their original
      conformation and restore function. Since many muscle wasting conditions have
      pathophysiologies where inflammation, atrophy and weakness are indicated,
      increasing HSP expression in skeletal muscle may have therapeutic potential. This
      review will provide evidence supporting HSP induction for muscular dystrophy and
      other muscle wasting conditions.This article is part of the theme issue 'Heat
      shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203714
TI  - Exercise, heat shock proteins and insulin resistance.
AB  - Best known as chaperones, heat shock proteins (HSPs) also have roles in cell
      signalling and regulation of metabolism. Rodent studies demonstrate that heat
      treatment, transgenic overexpression and pharmacological induction of HSP72
      prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin
      resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to
      increase endurance running capacity nearly twofold and increase mitochondrial
      content by 50%. A positive correlation between HSP72 mRNA expression and
      mitochondrial enzyme activity has been observed in human skeletal muscle, and
      HSP72 expression is markedly decreased in skeletal muscle of insulin resistant
      and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate
      with insulin resistance and non-alcoholic fatty liver disease progression in
      livers from obese patients. These data suggest the targeted induction of HSPs
      could be a therapeutic approach for preventing metabolic disease by maintaining
      the body's natural stress response. Exercise elicits a number of metabolic
      adaptations and is a powerful tool in the prevention and treatment of insulin
      resistance. Exercise training is also a stimulus for increased HSP expression.
      Although the underlying mechanism(s) for exercise-induced HSP expression are
      currently unknown, the HSP response may be critical for the beneficial metabolic
      effects of exercise. Exercise-induced extracellular HSP release may also
      contribute to metabolic homeostasis by actively restoring HSP72 content in
      insulin resistant tissues containing low endogenous levels of HSPs.This article
      is part of the theme issue 'Heat shock proteins as modulators and therapeutic
      targets of chronic disease: an integrated perspective'.

PMID- 29203716
TI  - Immune tolerance therapies for autoimmune diseases based on heat shock protein T
      cell epitopes.
AB  - Experimental models of autoimmune diseases have revealed the disease protective
      role of heat shock proteins (HSPs). Both the administration of exogenous
      extracellular, mostly recombinant, HSP and the experimental co-induction of
      endogenous intracellular HSP in models have been shown to lead to production of
      disease protective regulatory T cells (Tregs). Similar to HSP taken up from
      extracellular bodily fluids, due to stress-related autophagy upregulated HSP also
      from intracellular sources is a major provider for the major histocompatibility
      class II (MHCII) ligandome; therefore, both extracellular and intracellular HSP
      can be prominent targets of Treg. The development of therapeutic peptide vaccines
      for the restoration of immune tolerance in inflammatory diseases is an area of
      intensive research. In this area, HSPs are a target for tolerance-inducing T-cell
      therapy, because of their wide expression in inflamed tissues. In humans, in whom
      the actual disease trigger is frequently unknown, HSP peptides offer chances for
      tolerance-promoting interventions through induction of HSP-specific Treg.
      Recently, we have shown the ability of a bacterial HSP70-derived peptide, HSP70
      B29, to induce HSP-specific Tregs that suppressed arthritis by cross-recognition
      of their mammalian HSP70 homologues, abundantly present in the MHCII ligandome of
      stressed mouse and human antigen-presenting cells in inflamed tissues.This
      article is part of the theme issue 'Heat shock proteins as modulators and
      therapeutic targets of chronic disease: an integrated perspective'.

PMID- 29203715
TI  - The role of heat shock proteins and co-chaperones in heart failure.
AB  - The ongoing contractile and metabolic demands of the heart require a tight
      control over protein quality control, including the maintenance of protein
      folding, turnover and synthesis. In heart disease, increases in mechanical and
      oxidative stresses, post-translational modifications (e.g., phosphorylation), for
      example, decrease protein stability to favour misfolding in myocardial
      infarction, heart failure or ageing. These misfolded proteins are toxic to
      cardiomyocytes, directly contributing to the common accumulation found in human
      heart failure. One of the critical class of proteins involved in protecting the
      heart against these threats are molecular chaperones, including the heat shock
      protein70 (HSP70), HSP90 and co-chaperones CHIP (carboxy terminus of Hsp70
      interacting protein, encoded by the Stub1 gene) and BAG-3 (BCL2-associated
      athanogene 3). Here, we review their emerging roles in the maintenance of
      cardiomyocytes in human and experimental models of heart failure, including their
      roles in facilitating the removal of misfolded and degraded proteins, inhibiting
      apoptosis and maintaining the structural integrity of the sarcomere and
      regulation of nuclear receptors. Furthermore, we discuss emerging evidence of
      increased expression of extracellular HSP70, HSP90 and BAG-3 in heart failure,
      with complementary independent roles from intracellular functions with important
      therapeutic and diagnostic considerations. While our understanding of these major
      HSPs in heart failure is incomplete, there is a clear potential role for
      therapeutic modulation of HSPs in heart failure with important contextual
      considerations to counteract the imbalance of protein damage and endogenous
      protein quality control systems.This article is part of the theme issue 'Heat
      shock proteins as modulators and therapeutic targets of chronic disease: an
      integrated perspective'.

PMID- 29203719
TI  - An Ediacaran pre-placozoan alternative to the pre-sponge route towards the
      Cambrian explosion of animal life: a comment on Cavalier-Smith 2017.

PMID- 29203717
TI  - Hsp90 and FKBP51: complex regulators of psychiatric diseases.
AB  - Mood disorders affect nearly a quarter of the world's population. Therefore,
      understanding the molecular mechanisms underlying these conditions is of great
      importance. FK-506 binding protein 5 (FKBP5) encodes the FKBP51 protein, a heat
      shock protein 90 kDa (Hsp90) co-chaperone, and is a risk factor for several
      affective disorders. FKBP51, in coordination with Hsp90, regulates glucocorticoid
      receptor (GR) activity via a short negative feedback loop. This signalling
      pathway rapidly restores homeostasis in the hypothalamic-pituitary-adrenal (HPA)
      axis following stress. Expression of FKBP5 increases with age through reduced DNA
      methylation. High levels of FKBP51 are linked to GR resistance and reduced stress
      coping behaviour. Moreover, common allelic variants in the FKBP5 gene are
      associated with increased risk of developing affective disorders like anxiety,
      depression and post-traumatic stress disorder (PTSD). This review highlights the
      current understanding of the Hsp90 co-chaperone, FKBP5, in disease from both
      human and animal studies. In addition, FKBP5 genetic implications in the clinic
      involving life stress exposure, gender differences and treatment outcomes are
      discussed.This article is part of the theme issue 'Heat shock proteins as
      modulators and therapeutic targets of chronic disease: an integrated
      perspective'.

PMID- 29203720
TI  - Vendozoa and selective forces on animal origin and early diversification: reply
      to Dufour and McIlroy (2017).

PMID- 29203721
TI  - Correction to 'Lost in transmission...?'

PMID- 29203718
TI  - DNAJ Proteins in neurodegeneration: essential and protective factors.
AB  - Maintenance of protein homeostasis is vitally important in post-mitotic cells,
      particularly neurons. Neurodegenerative diseases such as polyglutamine expansion
      disorders-like Huntington's disease or spinocerebellar ataxia (SCA), Alzheimer's
      disease, fronto-temporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and
      Parkinson's disease-are often characterized by the presence of inclusions of
      aggregated protein. Neurons contain complex protein networks dedicated to protein
      quality control and maintaining protein homeostasis, or proteostasis. Molecular
      chaperones are a class of proteins with prominent roles in maintaining
      proteostasis, which act to bind and shield hydrophobic regions of nascent or
      misfolded proteins while allowing correct folding, conformational changes and
      enabling quality control. There are many different families of molecular
      chaperones with multiple functions in proteostasis. The DNAJ family of molecular
      chaperones is the largest chaperone family and is defined by the J-domain, which
      regulates the function of HSP70 chaperones. DNAJ proteins can also have multiple
      other protein domains such as ubiquitin-interacting motifs or clathrin-binding
      domains leading to diverse and specific roles in the cell, including targeting
      client proteins for degradation via the proteasome, chaperone-mediated autophagy
      and uncoating clathrin-coated vesicles. DNAJ proteins can also contain ER-signal
      peptides or mitochondrial leader sequences, targeting them to specific organelles
      in the cell. In this review, we discuss the multiple roles of DNAJ proteins and
      in particular focus on the role of DNAJ proteins in protecting against
      neurodegenerative diseases caused by misfolded proteins. We also discuss the role
      of DNAJ proteins as direct causes of inherited neurodegeneration via mutations in
      DNAJ family genes.This article is part of the theme issue 'Heat shock proteins as
      modulators and therapeutic targets of chronic disease: an integrated
      perspective'.

PMID- 29203722
TI  - What do polymorphisms tell us about the mechanisms of COPD?
AB  - COPD (chronic obstructive pulmonary disease) is characterized by irreversible
      lung airflow obstruction. Cigarette smoke is the major risk factor for COPD
      development. However, only a minority number of smokers develop COPD, and there
      are substantial variations in lung function among smokers, suggesting that
      genetic determinants in COPD susceptibility. During the past decade, genome-wide
      association studies and exome sequencing have been instrumental to identify the
      genetic determinants of complex traits, including COPD. Focused studies have
      revealed mechanisms by which genetic variants contribute to COPD and have led to
      novel insights in COPD pathogenesis. Through functional investigations of causal
      variants in COPD, from the proteinase-antiproteinase theory to emerging roles of
      developmental pathways (such as Hedgehog and Wnt pathways) in COPD, we have
      greatly expanded our understanding on this complex pulmonary disease. In this
      review, we critically review functional investigations on roles of genetic
      polymorphisms in COPD, and discuss future challenges and opportunities in
      discovering novel mechanisms of functional variants.

PMID- 29203724
TI  - Treatments for genital tract chlamydia infections during pregnancy.

PMID- 29203723
TI  - Oxidative stress and reactive oxygen species: a review of their role in ocular
      disease.
AB  - For many years, oxidative stress arising from the ubiquitous production of
      reactive oxygen species (ROS) has been implicated in the pathogenesis of various
      eye diseases. While emerging research has provided some evidence of the important
      physiological role of ROS in normal cell function, disease may arise where the
      concentration of ROS exceeds and overwhelms the body's natural defence against
      them. Additionally, ROS may induce genomic aberrations which affect cellular
      homoeostasis and may result in disease. This literature review examines the
      current evidence for the role of oxidative stress in important ocular diseases
      with a view to identifying potential therapeutic targets for future study. The
      need is particularly pressing in developing treatments for conditions which
      remain notoriously difficult to treat, including glaucoma, diabetic retinopathy
      and age-related macular degeneration.

PMID- 29203725
TI  - OTC miconazole oral gel contraindicated in patients taking warfarin.

PMID- 29203726
TI  - DOACs and risk of major bleeding with concomitant medicines.

PMID- 29203727
TI  - Anti-IL-5 therapies for asthma.

PMID- 29203728
TI  - Outcomes for cancer drugs approved in Europe.

PMID- 29203729
TI  - Interstitial fluid glucose monitoring system.

PMID- 29203730
TI  - Assessment of HPV vaccination programme.

PMID- 29203731
TI  - Mechanical thrombectomy and rescue therapy for intracranial large artery
      occlusion with underlying atherosclerosis.
AB  - OBJECTIVE: To investigate the safety and efficacy of mechanical thrombectomy plus
      rescue therapy for intracranial large artery occlusion (ILAO) with underlying
      intracranial atherosclerosis (ICAS). METHODS: Patients enrolled in the
      intervention group of EAST (Endovascular Therapy for Acute ischemic Stroke Trial)
      were analyzed. For underlying ICAS identified during the stent retrieval
      procedure, rescue treatment was required for those with (1) a degree of arterial
      stenosis >70% or (2) any degree of arterial with blood flow impairment or (3)
      evidence of re-occlusion. Outcomes were compared between the ICAS group and the
      embolic group. Multivariate logistic regression was performed to determine
      independent predictors of functional independence at 90 days. RESULTS: Among the
      140 patients included in the analysis, underlying ICAS was identified in 47
      (34%), and 30 patients (21.4%) were considered to be eligible to receive rescue
      treatment. Of the 30 patients, 27 (90%) actually received rescue therapy.
      Recanalization rate (95.7% vs 96.8%, P=0.757) and functional independence at 90
      days (63.8% vs 51.6%, P=0.169) were comparable between the ICAS group and the
      embolic group. No significant difference in symptomatic hemorrhage (4.3% vs 4.3%,
      P=1.000) or death (12.8% vs 12.9%, P=0.982) was found between the two groups.
      National Institutes of Health Stroke Scale score at presentation (OR=0.865, 95%
      CI 0.795 to 0.941; P=0.001) and modified Thrombolysis in Cerebral Infarction
      after the procedure (OR=2.864, 95% CI 1.018 to 8.061; P=0.046) were independently
      associated with functional independence at 90 days. CONCLUSIONS: Mechanical
      thrombectomy is safe in patients with ILAO with underlying ICAS. By employing a
      standard rescue therapy, favorable outcomes could be achieved in such patients.
      CLINICAL TRIAL REGISTRATION: NCT02350283 (Post-results).

PMID- 29203732
TI  - X-ray angiography perfusion imaging with an intra-arterial injection: comparative
      study with 15O-gas/water positron emission tomography.
AB  - BACKGROUND: X-ray angiography perfusion (XAP) is a perfusion imaging technique
      based on conventional DSA. OBJECTIVE: In this study, we aimed to validate
      parameters derived from XAP by comparing them with 15O-gas/water positron
      emission tomography (PET), using data from patients with chronic ischemic
      cerebrovascular disease. METHODS: 18 consecutive patients were included. XAP was
      performed with intra-arterial infusion of contrast media, and a time-density
      curve was constructed for each cerebral hemisphere. From the curves, the relative
      values of mean transit time (rMTT) and wash-in rate (rWiR) were obtained by
      dividing the values of the right hemisphere by those of the left hemisphere.
      These were then compared with the relative values of cerebral blood flow (rCBF)
      and rMTT calculated from the PET data. RESULTS: XAP rWiR correlated strongly with
      PET rCBF (r=0.86, P<0.0001). rMTT measurements from the two modalities were also
      strongly correlated (r=0.85, P<0.0001). Bland-Altman analysis revealed a bias of
      0.14+/-0.18 (95% limits of agreement -0.22 to 0.51) for PET rCBF versus XAP rWiR,
      and 0.016+/-0.093 (95% limits of agreement -0.17 to 0.20) for rMTT between the
      two modalities. CONCLUSIONS: The relative values obtained from XAP were validated
      across a population of patients with chronic ischemic cerebrovascular disease.

PMID- 29203733
TI  - [Assessment of knowledge about hypothermia among the medical personnel of polish
      medical air rescue].
AB  - : Polish Medical Air Rescue is tasked to deal with the most serious incidents
      associated with life threatening situations, in multiple circumstances. As a
      consequence, medical personnel have to meet high standards of education and show
      a continuous theoretical and practical development of the skills which are
      necessary during medical treatment. Thanks to the introduction of ECMO treatment
      for accidental hypothermia patients, new clinical and operational possibilities
      have arisen, so more patients can be saved with a very good neurological outcome.
      AIM: To analyze the data on hypothermia collected by the personnel of Polish
      Medical Air Rescue and to assess the e-learning platform as an educational tool.
      MATERIALS AND METHODS: 123 persons were involved. The subject of analysis were
      the e-learning platform results of the Polish Medical Air Rescue medical
      personnel. The e-learning consisted of a pre-test, 8 lessons followed by MCQ's
      (multi choice questions) and a post-test. RESULTS AND CONCLUSIONS: We could not
      prove a statistically significant difference in the knowledge about hypothermia
      between doctors and other medical professionals. Post-traumatic hypothermia and
      associated coagulation disturbances are two important topics requiring particular
      focus during the design of further educational and training projects. As a
      consequence of the training, both groups significantly improved their knowledge:
      i.e. a statistically significant improvement of knowledge about hypothermia
      between pre-test and post-test results in both groups was shown. The hypothermia
      e-learning platform for medical personnel is an effective educational tool.

PMID- 29203734
TI  - Effect of pioglitazone on insulin resistance, progression of atherosclerosis and
      clinical course of coronary heart disease.
AB  - INTRODUCTION: Pioglitazone, a medication of thiazolidinedione group, is capable
      of triggering the peroxisome proliferator-activated receptors (PPAR-gamma).
      Activation of receptor PPAR-gamma regulates carbohydrate and lipid metabolism,
      immune and inflammatory responses in heart tissues. THE AIM: Our aim was to study
      the effect of pioglitazone on insulin resistance, the clinical course of
      atherosclerosis and coronary heart disease (CHD). MATERIALS AND METHODS: The
      study included 43 patients with coronary artery disease. Patients were divided
      into the main group - 20 patients, in whom pioglitazone (Pioglar, Ranbaxy, India)
      was included in the combined therapy at a dose of 15 mg 1 time per day in the
      morning, and the comparison group - 23 patients receiving standard complex drug
      therapy over 6 months. Patients underwent clinical examination, ultrasound of
      neck vessels, study of carbohydrate and lipid metabolism. RESULTS: Joining
      pioglitazone to standard therapy resulted in the reduction of systolic (p<0.05)
      and diastolic (p<0.05) blood pressure; decrease in the duration of pain attacks
      (p<0.05); reduction in the frequency of angina attacks (p<0.05); regression of
      atherosclerosis of the carotid vessels (p<0.05), decrease in the thickness of the
      intima-media complex (p<0.05). The decline in oral glucose tolerance test
      (p<0.05), hyperglycemic factor (p<0.05), total cholesterol (p<0.05), and low
      density lipoproteins (p<0.05) were observed, as well as increased high-density
      lipoprotein (p<0.05). CONCLUSION: Long-term treatment with pioglitazone at low
      doses against the background of standard therapy contributes to functional and
      clinical condition of patients, promotes the prevention of atherosclerosis and
      reduction of insulin resistance, thereby improving the clinical manifestations of
      coronary heart disease.

PMID- 29203735
TI  - Histomorphologic changes of esophageal mucosa in experimental third degree
      stricture.
AB  - INTRODUCTION: Nowadays the level of early and late complications after the
      operations for esophageal corrosive strictures such as esophago-organ anastomotic
      leak, development of infections, pneumonia, pleural empyema, mediastinitis,
      peritonitis, postoperative corrosive stricture development etc. remains rather
      high. Besides, postoperative mortality rate is high as well - 3.5-30 %. For that
      reason, an experimental model of esophageal stricture was suggested and
      ultrastructural mucosal changes in the stricture itself were studied to elaborate
      the unified pathogenic approach in treatment of esophageal stricture and
      improvement of its results. The aim of our work was to study the dynamics of
      ultrastructural changes both in normal esophageal walls and in third degree
      esophageal stricture Materials and Methods: The experiment was carried out on
      white male rats weighting 250-300 grams, to whom the third degree esophageal
      stricture model was created. After layer-by-layer incision of anterior abdominal
      wall abdominal portion of the esophagus was completely ligated (10 rats). In the
      control group (6 rats) anterior abdominal wall was opened with its subsequent
      layered closure. The animals were withdrawn from the experiment on the third day
      by ketamine overdose, and the samples were taken for ultrastructural study.
      RESULTS: Electron microscopic study of submicroscopic organization of basal,
      prickle, superficial epithelial cells in stratified non-squamous epithelium,
      smooth myocytes of muscle plate and contractile elements in esophageal muscular
      layer was carried out. Nuclear membrane, membranes of mitochondria, endoplasmic
      reticulum and cytoplasmic Golgi complex were found to be subjected to focal
      lysis. The third degree esophageal stricture caused destructive lesions in
      ultrastructural architectonics of stratified non-squamous epithelium cells,
      smooth myocytes of muscle plate and contractile elements in esophageal muscular
      layer of rats. CONCLUSION: Thus, catabolic processes leading to organelle
      disintegration develop in esophageal cells of rats with third degree stricture.

PMID- 29203736
TI  - The exchange of monoamines during the experimental neurosis on the background of
      using of amide "2-hydroxy-n-naphthalen-1-yl-2-(2-oxo-,2-dihydroindol-3-ylidene)".
AB  - INTRODUCTION: Incessant increase in the frequency and distribution of anxiety
      disorders stipulates searching, research and study of the mechanism of action of
      new substances for their correction, including the group of 2-oxoindolin-3
      glyoxylic acid derivatives. THE AIM: To research the effect of N-(1-naphthyl)
      amide-2-oxoindolin-3-glyoxylic acid on monoaminergic system of subjected to
      experimental neurosis of rats. MATERIALS AND METHODS: The experiments were
      performed on male Wistar rats, who have weight 180-220g and were researching the
      effect of 2-hydro-N-naphthalen-1-yl-2-(2-oxy-1,2-dihydroindol-3-ylidene)
      acetamide (compound 18) at a dose (12 mg/kg), by intragastric drug injection of
      subjected to experimental neurosis rats, during 30 days (1 time in three days),
      for monoamines content (epinephrine, norepinephrine, dopamine and serotonin) in
      the blood, their decay products (homovanillic acid, vanillylmandelic acid and 5
      oxyindolacetic acid) in the urine and the ratio of end products of the reaction
      to their predecessors. RESEARCH: It was established that during the preventive
      therapeutic application of N-(1-naphthyl)amide-2-oxoindolin-3-glyoxylic acid, it
      effectively adjusts the level of monoamines, reducing the content of adrenaline
      and increasing the content of noradrenaline, dopamine and 5-HT in the blood. The
      compound also reduces the content of products exchange of mediators (HVA,VMA and
      5-OIAA) in the urine. The 2-oxoindolin derivatives reduces the ratio between
      HVA/dopamine, VMA/(noradrenaline + adrenaline) and 5-OIAA/5-HT, it testifies
      about the normalizing of enzymes activity, which are involved in the process of
      exchange and maintaining the constancy of monoamines. The results show that in
      the mechanisms of anxiolytic action of compound 18, a significant role plays the
      normalization of content and exchange of neurotransmitters in the organism, which
      caused an experimental neurosis. CONCLUSION: Compound 2-hydro-N-naphthalen-1-yl-2
      (2-oxo-1,2-dihydroindol-3-ylidene)-acetamide by the experimental 30-day neurosis,
      was reducing the expression of neurotransmitter imbalance in the blood,
      apparently due to correction of enzymatic synthesis links and biotransformation
      of monoamines.

PMID- 29203737
TI  - [Pertussis in children with incomplete active immunization].
AB  - INTRODUCTION: In recent years, a significant increase in the incidence of
      pertussis among children has been observed both in Ukraine and worldwide. Infants
      who were partially vaccinated or children who became ill in a short time after
      complete active immunization with primary vaccination complex against pertussis
      are more often referred to our clinic with the diagnosis of "pertussis". THE AIM:
      The clinical peculiarities of pertussis study in partially vaccinated infants and
      infants who are in the process of vaccination against pertussis. MATERIALS AND
      METHODS: 83 infants aged 3-12 months in Lviv Regional Hospital of Infectious
      Diseases were kept under observation. The course of the disease and some
      laboratory dates have been investigated. Severity of pertussis was estimated by
      the Preziosi & Halloran score. RESULTS: Pertussis catarrhal period lasted
      significantly longer in partially vaccinated children. A shorter period of time
      during which cough with reprises persisted has been determined; a significant
      lower leukocytes levels and absolute amount of lymphocytes have been revealed
      both on admission and in the dynamics of the disease in vaccinated children as
      compared with unvaccinated patients. CONCLUSIONS: We have concluded that the
      children, who received 1, 2 and/or 3 inoculations during primary vaccination
      against pertussis in epidemics period, are at high risk for pertussis. The course
      of the disease in these children is reliably milder, with longer catarrhal
      period, less duration of spasmodic cough, fewer episodes of cough during the day,
      lower rate of complications.

PMID- 29203738
TI  - Mathematical model of diabetic encephalopathy.
AB  - INTRODUCTION: Diabetes mellitus (DM) is one of the leading risk factors for
      cerebrovascular disorders. The risk of stroke is 3-4 times higher in this
      population. In 10% of cases of vascular accidents in diabetic patients leads to
      fatal. The mortality rate for ischemic stroke is undergoing 50-60% and 70-95% of
      hemorrhagic form. It is known that diabetes increases the course of acute
      disorders of cerebral circulation. At the same time, there are data that about
      415 million of the inhabitants of the planet suffer from diabetes, in 95% of
      cases they have type 2 diabetes, which is the second risk factor for the
      development of ischemic stroke after an arterial hypertension. This determines
      the relevance of studying the factors that affect the development of the ischemic
      process in patients with diabetes The aim of this research is to optimize the
      methods for diagnosis of diabetic encephalopathy based on a study of indicators
      of cerebrovascular hemodynamics, functional state of the brain, metabolic
      disorders and morphological characteristics of the brain tissue. MATERIALS AND
      METHODS: It was carried out a comprehensive survey of 537 patients with diabetes,
      including type 1 diabetes is set to 342 (63.7%) type 2 diabetes - in 195 (36.3%)
      patients. In 108 (20.1%) patients with diabetes, the clinical syndrome DE not
      identified in 429 (79.9%) - found DE I, II and stage III disease. CONCLUSIONS:
      Construction of mathematical model allows to objectify the diagnosis where with
      the help of clinical and metabolic parameters without expensive equipment. At the
      same time, the availability of informative indicators identified will allow the
      doctor to diagnose DE the early stages or to predict its development and to
      discover at the preclinical stage.

PMID- 29203739
TI  - 4 and 6 interleukin's action in the pathogenesis of periodontitis, gingivitis and
      dental alveolitis.
AB  - INTRODUCTION: The paper presents the results of studying the role of interleukins
      4 and 6 in the pathogenesis of periodontal tissue diseases, specifically, in
      periodontitis, gingivitis and alveolitis. THE AIM: To study the nature of
      participation of IL-4 and IL-6 in the mechanisms of development of periodontitis,
      gingivitis and alveolitis. MATERIALS AND METHODS: Studies were carried out on 80
      nonlinear male rats with a body weight of 200.0 to 220.0 g divided into four
      groups of 20 animals each. The serum level of cytokines was determined by an
      enzyme immunoassay on the Multiscane Biotech analyzer using test systems
      manufactured by Caltag laboratories (USA). Statistical processing of the obtained
      digital results was processed with the help of the program "Statistica 8.0".
      Indicators of the reliability of changes between the control and intact groups
      also used the Student's test and the Excel program. The confidence level was
      taken at p <0.05. RESULTS: As a result of our experiments, noticeable changes in
      the anti-inflammatory cytokine IL-4 were observed in rats with experimental
      periodontitis. The level of IL-4 cytokine in rats with alveolitis did not differ
      from control. The level of proinflammatory cytokine IL-6 from all groups of
      animals with periodontal disease differed from control only in rats with
      gingivitis, where it decreased by 74% and its level became less with alveolitis
      and periodontitis, since in these diseases the level of IL-6 was practically the
      same from the control (p <0,05). We also succeeded in revealing that at a low
      level of profibrogenic IL-6, there is not enough stimulation of collagen
      synthesis in the periodontal bone tissue. The increased level of IL-4 in a group
      of animals with gingivitis, on the contrary, indicates the realization of a
      pathological reaction of the organism. CONCLUSIONS: The change in the levels of
      pro- and anti-inflammatory interleukins, especially with gingivitis, indicates a
      decrease in the body's adaptive reserves and may affect the further dynamics of
      the inflammatory process in the periodontal tissues.

PMID- 29203740
TI  - Optical density of upper jaw in patients with malocclusion.
AB  - INTRODUCTION: The growth and formation of facial skeleton is in interrelation
      with growth of cervical spine. Computer tomography plays an important role to
      examine and investigate the density of bony tissue resulting from total increase
      of osteopenic diseases and diseases of periodontal tissue. The aim of the paper
      is to compare indices of mineral density of bony tissue of the upper jaw and
      mineral density of the second cervical vertebra in patients with malocclusion.
      MATERIALS AND METHODS: 37 orthodontic patients were involved in the
      investigation. They were divided into three age groups depending on the period of
      formation of dentofacial system. Density measurement of bone of the second
      cervical vertebra was done and also density measurement of upper jaw in the area
      of alveolar process between central incisors, canines and the first premolar on
      the level of the middle of roots, in the area of the first molars under the level
      of bifurcation and in cusp was performed. RESULTS: Optical density of bone of the
      second cervical vertebra with age increases from 501+/-61,06 to 587,6+/-48,81.
      The densest area on the upper jaw is alveolar process between central incisors,
      which increases with age from 1045,14+/-59,81 to 1318+/-69,28. The least indices
      of optical density were determined in area of the cusp of the upper jaw: the
      first group presented 174,21+/-38,94, and the third one included 338,87+/-26,91.
      CONCLUSIONS: Densitometry of bony tissue with computer tomography is
      diagnostically informative and available method for investigation and it can be
      used for diagnostics of bony tissue condition and for evaluation of orthodontic
      treatment.

PMID- 29203741
TI  - [Studying of life's quality changes among children of the first three year of
      life with visual analyzer's congenital pathology as instrument of their social
      adaptation's formation in the future became a research objective].
AB  - INTRODUCTION: The study of the composite qualities of life is an important
      component of the quality of provided medical aid. The way of our investigation
      that was chosen by us, the quality of life of the children of first years of life
      with the congenital pathology of vision arises the significant problem of
      assessment of its changes, because children of these ages can't take part in an
      interview and we adapted the standard questionnaire "Children Visual Function
      Questionnaire" (CVFQ) with its help the components of quality of the children of
      first years of life assess their parents. THE AIM: Studying of life's quality
      changes among children of the first three year of life with visual analyzer's
      congenital pathology as instrument of their social adaptation's formation in the
      future became a research objective. MATERIALS AND METHODS: Out-patient and
      polyclinic units of Kyiv's healthcare institutions in which the medical care is
      provided to children of the first three years of life, particularly with
      congenital ophthalmic pathology (3 institutions) were scientific base of a
      research. We have been used the adapted version of the standardized questionnaire
      of Children's Visual Function Questionnaire (CVFQ) Felius et al were primary
      material. (2004) - 498 questionnaires, from them 398 of the main group and 100 of
      control. The purpose of a research required using the complex of research
      methods, a basis for which is a system approach, namely: medico-statistical and
      sociological (the respondents were informed about the purpose and research
      problems and timely gave the oral voluntary agreement in anonymous poll before
      the filling of questionnaires) methods. RESULTS: The results of a research has
      established that parents of children from control group have estimated the
      general condition of children's vision totally in 89,75 +/- 1,33 points vs 60,25
      +/- 1,96 points according to a total score of children's parents from the main
      group (the difference was 32,87%, at r<0,001). In general, the total number of
      points was 64,89 +/- 1,01 vs 84,67 +/- 0,92, with a difference in 23,4% (r<0,001)
      in the main group, according to life's quality total score of early years
      children's parents. Our research proves existence of children's life quality
      changes at the presence of visual violations among them that substantiates
      expediency of strengthening of early identification and treatment measures of
      visual function's violations at children, within the approved medico
      technological documents. CONCLUSION: Interaction in form of cooperation between
      the family doctor and children's ophthalmologist within the competences on
      maintaining children with visual analyzer's violation of functions from the first
      days of life, allows to perform effective long observation of a family,
      preventing development of medico-social disadaptation both the child, and a
      family in which it appeared. Research results of life's quality components
      changes are informative for a future social functioning of the child, his family,
      the parent's attitude to a child's disease and it's treatments, and performance
      of disease's treatment.

PMID- 29203742
TI  - Neutrophil bactericidal activity through the stages of placement of different
      dental implants depending on their chemical composition.
AB  - INTRODUCTION: The analysis of data provided by implant system manufacturers has
      demonstrated that implants, i.e. parts screwed into the bone, are of different
      chemical composition of the implant. Sometimes they have little amount of metal
      contaminants,which are not biologically passive. THE AIM: To explore the effects
      produced by dental titanium implants containing metal contaminants on the
      stimulation of antimicrobial properties of neutrophils. MATERIAL AND METHODS: A
      total of 24 patients who had from 1 to 4 titanium implants with different
      chemical compositions were subjected to the comprehensive check-up to this end.
      The functional activity of neutrophils was evaluated by nitroblue tetrazolium
      (NBT) reduction test. It was dynamically in 5-7 days after the implant fitting
      into the bone, and in 3 months after the procedure of implant placement. RESULTS:
      On the 5-7th day following the placement of implants with weight percentage of
      titanium (Ti) in the composition from 25 to 50%, the share of active neutrophils
      significantly increased compared with share of active neutrophils prior the
      surgical procedure. However, after 3 months, this parameter in patients with
      implants, whose titanium content was low, remained significantly high.
      CONCLUSIONS: The placement of dental implants systems led to an increase in the
      share of active neutrophils in the peripheral blood of the patients in 5-7 days
      following the procedure of implant insertion. However, this indicator for implant
      systems with a higher content of Ti in the remote period returned to its original
      value, which indicates their higher biocompatibility with the tissues of the
      human body.

PMID- 29203743
TI  - Analysis of major risk factors affecting those working in the agrarian sector
      (based on a sociological survey).
AB  - INTRODUCTION: Issues related to labour potential, its state and problems have
      consistently been a focus of attention for the International Labour Organisation
      (ILO). Its respective analysis shows that labour potential problems remain
      unresolved in many countries of the world. According to the World Health
      Organisation (WHO), adverse working conditions are among major factors of
      occupational disease development in Europe and the reason for disabilities of
      economically active population during 2.5% of their lifetime. The aim of the
      present study is to identify and analyse major risk factors, which have a bearing
      on people working in agriculture in the course of exercising their occupation,
      with account of forms of ownership of agricultural enterprises. MATERIAL AND
      METHODS: Carried out was a cross-sectional study involving a sociological survey
      of 412 respondents - those working in agriculture - who made up the primary group
      and the control group. The study revealed 21 risk factors, 9 of which were work
      related. A modified elementary cybernetic model of studying impact efficiency was
      developed with the view of carrying out a structural analysis of the sample group
      and choosing relevant methodological approaches. RESULTS: It has been established
      that harmful factors related to working environment and one's lifestyle are
      decisive in the agrarian sector, particularly for workers of privately owned
      businesses. For one out of three respondents harmful working conditions
      manifested themselves as industrial noise (31.7+/-3.4), vibration (29.0+/-2.1)
      trunk bending and constrained working posture (36.6+/-3.4). The vast majority of
      agricultural workers (91.6+/-2.5) admitted they could not afford proper rest
      during their annual leave; male respondents abused alcohol (70.6+/-3.0) and
      smoking (41.4+/-2.0 per 100 workers). CONCLUSION: The research established the
      structure of risk factors, which is sequentially represented by the following
      groups: behavioral (smoking, drinking of alcohol, rest during annual leave,
      physical culture), working environment and work activities (occupation, work
      experience, safety measures, working environment, organization and management),
      socioeconomic (education, financial situation).

PMID- 29203744
TI  - Differences in clinical manifestations of odontogenic and non-odontogenic
      lymphadenitis.
AB  - INTRODUCTION: The acute suppurative lymphadenitis and its chronic forms prevail
      in the structure of inflammatory processes of the maxillofacial area in children.
      High incidence of the acute and chronic forms of lymphadenitis of both
      odontogenic and nonodontogenic origin is caused by the anotomophysiological
      peculiarities of the structure of the teeth and soft tissues in children in
      different age periods. THE AIM: The paper was aimed at comparison of clinical
      manifestations of the acute and chronic odontogenic and non-odontogenic
      lymphadenitis. MATERIALS AND METHODS: The results of the checkup and 5-year
      period treatment of 324 children with the acute and chronic forms of the
      nonspecific lymphadenitis of the maxilifacial area have been used. Four study
      groups have been formed. The first and the second group included 16 (38,0%) and
      26 (62%) children with the acute submandibular suppurative lymphadenitis of the
      odontogenic and nonodontogenic origin, respectively. 12 (35,3%) and 22 (64,7)
      individuals with chronic hyperplastic lymphadenitis have been assigned to the
      third and the fourth group, respectively. RESULTS: The clinical course of the
      acute submandibular suppurative lymphadenitis of various etiologies is different.
      Rapid development of the local clinical manifestations with its dramatic
      progressing is specific to odontogenic lymphadenitis. Its clinical course is
      characterized by the more apparent overall response of the body, increase of the
      body temperature, and these symptoms are more manifested than in nonodontogenic
      lymphadenitis. The clinical course of chronic hyperplastic lymphadenitis is
      accompanied by the enlarged regional lymph nodes of various size and shapes and
      dense-elastic consistency. Clinical manifestations of nonodontogenic
      lymphadenitis were less apparent and the overall sate was normal in both forms of
      lymphadenitis. CONCLUSIONS: Nonodontogenic lymphadenitis prevailed in all
      nosological forms of the acute and chronic nonspecific lymphadenitis.

PMID- 29203745
TI  - The use of morphological study technique for investigation of labial and palatine
      glands.
AB  - INTRODUCTION: Due to the deterioration of environmental conditions that promotes
      the onset of inflammatory and autoimmune diseases, and the progress in the
      diagnosis, the frequency of registration of intercurrent pathology of salivary
      glands has markedly risen in recent years, demonstrating the increased scientific
      interest in the research of the common and distinctive features of their
      structure. THE AIM: The paper was aimed at the development of the method of
      morphological study of human minor salivary (labial and palatine) glands by the
      use of plastic wax reconstruction to obtain the plastic model of the acini and
      ducts of human minor salivary glands. MATERIALS AND METHODS: Specimens of the
      glandular area of the hard palate mucosa and labial mucosa in its middle third
      have been studied. To gain the objective of the investigation the technique for
      morphological study of the human minor salivary (labial and palatine) glands is
      to be developed, encompassing the analysis of the spatial organization of the
      glandular epithelium of the labial and palatine glands together with blood
      microcirculatory flow by fixing the obtained specimens of the minor salivary
      glands in 4% glutaraldehyde solution and osmium tetroxide with subsequent
      embedding into the Epon-812, staining the serial semi-thin sections with
      phosphate buffered 0,1% toluidine blue solution, photomacrography of the
      distinguished boundaries of the investigated structures and obtaining of
      photoreconstructions. RESULTS AND CONCLUSIONS: Thus, the use of suggested
      technique enables to obtain the megascopic reconstruction of the acini and ducts
      of the labial and palatine glands, which can be studied from different sides,
      getting the full visualization of the shape and size, as well as to explore the
      glands' inner configuration, the geometry of the lumen of the epithelial
      excretory ducts, to determine changes in the thickness of the wall, to get a
      visual representation of the microtopographic interactions between the different
      parts of blood microcirculatory flow and excretory ducts of the minor salivary
      glands.

PMID- 29203746
TI  - [Effectiveness of early physiotherapy treatment for ischaemic stroke patients
      suffering intercurrently from post-stroke depression and/or hemispatial neglect
      syndromes].
AB  - Wstep: Depresja poudarowa i zespol pomijania stronnego sa jednymi z szeregu
      zaburzen neurologicznych wystepujacych jako konsekwencje incydentu udarowego. Oba
      zaburzenia uwaza sie za czynniki negatywnie wplywajace na szybszy powrot pacjenta
      do zdrowia. Zadaniem wczesnej fizjoterapii po incydencie udarowym jest poprawa
      funkcji motorycznych oraz poprawa jakosci zycia pacjenta. Material i metody: W
      badaniu wzielo udzial 51 pacjentow zakwalifikowanych do wziecia udzialu w
      "Narodowym Programie Profilaktyki i Leczenia Chorob Ukladu Sercowo-Naczyniowego
      na lata 2006-2008 POLCARD". Wyniki badan pacjentow notowano w skali Barthel, NIH
      oraz Geriatrycznej Skali Oceny Depresji. Analiza statystyczna zostala wykonana w
      programie STATISTICA 6PL za pomoca testu Wilcoxona dla prob zaleznych. Wyniki:
      Analiza wynikow wykazala, ze osoby z zespolem zaniedbywania osiagnely wiekszy
      przyrost punktow w skali Barthel niz osoby bez zespolu pomijania stronnego
      (p<=0,05). Natomiast badanie osob z depresja poudarowa wykazaly wiekszy przyrost
      punktow w skali Barthel niz pacjenci, u ktorych depresja nie zostala stwierdzona.
      Wnioski: Skutecznosc wczesnej fizjoterapii zalezy od ciezkosci udaru, stopnia
      niepelnosprawnosci oraz czynnikow zaburzajacych, takich jak m.in. agnozja
      wzrokowo-przestrzenna lub depresja. Jednakze pacjenci ze wspolistniejacymi
      zespolami neurologicznymi poddani kompleksowej fizjoterapii we wczesnym okresie
      po udarze mozgu maja prawdopodobnie wieksza rezyliencje w zakresie motywacji,
      zdolnosci adaptacyjno-kompensacyjnych, czyli generalnie dotyczacych plastycznosci
      mozgu.

PMID- 29203747
TI  - [Effect of antioxidants on human primary and metastatic colon cancer cells at
      hypoxia and normoxia].
AB  - THE AIM: Evaluation of some antioxidants on human colon cancer cells viability
      and proliferation at various oxygen levels. MATERIAL AND METHODS: Human primary
      (SW480) and metastatic (SW620) colon cancer cells were cultured at hypoxia (1%
      oxygen), tissues (10% oxygen) and atmospheric (21% oxygen) normoxia with
      quercetin, epigallocatechin gallate, lipoic acid, hydroxycitric acid, their
      mixture, and without studied compounds (control). Antioxidants were used at
      physiological concentrations. The cell viability was determined by trypan blue
      dye exclusion and proliferation by MTT assay. RESULTS: The viability of each line
      ranged from 80% to 97%, and it was independent on the compound and oxygen
      availability. At hypoxia the cell count of both lines was lower than for the
      controls in the presence of each studied compound. At tissue normoxia the cell
      count of primary cancer cells was decreased only with epigallocatechin gallate,
      whereas metastatic cells were sensitive for each antioxidant. CONCLUSIONS: Our
      results indicated, that the studied antioxidants were not cytotoxic at
      physiological levels for both pirmary and metastatic colon cancer. Their
      cytostatic effect depend on the type of cell, oxygen availability and antioxidant
      concentration.

PMID- 29203748
TI  - International legal regulation of impact of occupational injuries and diseases on
      agricultural workers' health.
AB  - INTRODUCTION: Agricultural workers' health depends on many factors: working
      conditions, security arrangements, medicine, quality of drugs, the environment,
      etc. Occupational injuries and diseases are also among the factors that can
      negatively affect their health. THE AIM: To analyze provisions of the
      international legislation and scientific literature concerning existence of
      restrictions on impact of occupational injuries and diseases on agricultural
      workers' health. MATERIALS AND METHODS: International acts, data of international
      organizations and conclusions of scientists have been examined and used in the
      study. The article also integrates information from scientific journals and
      monographs from a medical and legal point of view with scientific methods. This
      article is based on dialectical, comparative, analytic, synthetic and
      comprehensive research methods. Impact of occupational injuries and diseases on
      agricultural workers' health has been studied within the system approach, as well
      as analysis and synthesis. CONCLUSIONS: The level of occupational morbidity,
      traumatism and above all standard of agricultural workers' health depends on the
      way of occupational safety organization. Working conditions and safety in
      agricultural industry and therefore the appropriate standard of health remain
      unsatisfactory in many countries.

PMID- 29203749
TI  - Didactic aspects of cognition of human as a bio-psycho-socio-cultural
      personality.
AB  - Modern education, according to leading Ukrainian scientists, requires the
      development of a new paradigm, which will consider the phenomenon of man
      holistically. The article describes didactic aspects of cognition of human as a
      bio-psycho-socio-cultural personality, as social fact, as a phenomenon. For the
      actualization of the didactic aspects of the problem, the authors used the
      methods of scientific literature analysis, systemic analysis and generalizations,
      analysis own practice of didactic and methodological character. Reforming the
      systems of education and medicine should occur in the context of providing
      active, creative, productive human life. Practice of system analysis proved that
      man as a subject of study should be considered as a biological entity, a social
      being, the bearer of consciousness and culture. A holistic approach to the study
      of man, viewing him as creatures of the natural (bodily) and social individual
      (society, culture) and the subject of mental and spiritual (creative and
      deliberate) activity can reveal its unique originality. The uniqueness of the
      phenomenon of man as the subject and object of research lies in its
      indivisibility, which is based on the unity of the laws of nature and society.
      Therefore, when studying the person should take into account the interests of
      social and natural Sciences. This once again confirms the idea of the necessity
      of human studies with the help of a systematic approach, which generates true and
      holistic view of the person, that involves the development of meta-perception of
      world and ourselves.

PMID- 29203750
TI  - Concept of waste and its impact on human health.
AB  - INTRODUCTION: Impact of the environment on human health is increasingly being
      paid attention both at the international level and at the level of individual
      countries. Among the factors that anyhow can affect it negatively, various
      objects are distinguished and waste is not of the last consequence. It has
      different nature of origin, ways of further utilization and a degree of impact on
      human health and the environment. Its generation, utilization and neutralization
      are determined by the relevant processes; their research allows continuous
      improvement and reduction of their negative impact on human health and the
      environment. THE AIM: To analyze provisions of the international legislation
      concerning the concept of waste and its classification, as well as its potential
      impacts on human health and the environment. MATERIALS AND METHODS: The study
      analyzes and uses international legal documents, data of international
      organizations and scientists' deductions. Furthermore, the study integrates
      information from scientific journals with scientific methods from the medical and
      legal point of view. Within the framework of the system approach, as well as
      analysis and synthesis, the concept of waste, its classification and impact on
      human health and the environment have been researched. RESULTS: In consequence of
      the conducted study, it has been found that at the European level, considerable
      attention is paid to waste in the context of its possible negative impact on
      human health and the environment. Solution of this problem is carried out with
      the integrated approach, which is expressed both in enacting statutory acts and
      amending existing ones, as well as elucidating various aspects at the scientific,
      methodological, statistical and other levels. CONCLUSIONS: Waste in itself has
      different nature of origin, negative impact, ways of its further utilization.
      Some kinds of it can be used further in order to achieve other goals and needs
      that are not related to their generation, others can no longer be used for human
      benefits taking into account existing achievements.

PMID- 29203751
TI  - [Metabolic syndrome - a new look at a known problem].
AB  - Civilization changes over the past decades have been associated with an increase
      in the incidence of various metabolic disorders, especially in the carbohydrate
      lipid metabolism, which are not always associated with obesity. Metabolic
      syndrome, despite changing criteria of recognition, is a clinically established
      risk factor for civilization diseases development. On the other side, the
      incidence of complex metabolic disorders in non-obese people is increasing, which
      is referred to in the literature as metabolic obesity with normal body mass.
      Both, excess visceral fatty tissue and insulin resistance are common components
      in the diagnosis of these syndromes and their occurrence is associated with an
      increased risk of developing type 2 diabetes and cardiovascular disease. Some
      researchers also point out the possibility of occurrence of so-called
      metabolically healthy obesity. Identify people with such a constellation of
      disorders is still difficult in clinical practice because of different and
      changing diagnostic criteria. Data from the literature about epidemiology of
      these disorders are inconclusive and do not allow for a reliable assessment of
      such disorders prevalence in population. The increasing rate of the metabolic
      syndrome and metabolic obesity with normal body weight occurrence in the general
      population pays attention to the importance of this problem, especially in
      primary health care. Preventive programs are primarily aimed at older people with
      high risk of cardiovascular diseases development and focused on detecting
      metabolic syndrome traits. Nevertheless, very often, young, potentially healthy
      individuals, are not subject to screening programs, even though incidence of
      metabolic obesity with normal body weight in this population is very high
      nowadays.

PMID- 29203752
TI  - [Cytotoxicity in vitro as the principal parameter for evaluation of
      biocompatibility of medical devices].
AB  - According to the Polish Ministry of Health decree, the medical devices and all
      raw materials used for their manufacturing are in force to be compatible with
      biological tissues, cells and body fluids regarding its clinical use. It is
      defined as biocompatibility. The scope of the methods proposed in the norm PN-EN
      ISO 10993-1 makes possible to get full preclinical characteristics of the medical
      device and allows to form the opinion about safety of it to the patients after
      its marketing. The test directed as the principal to make, independently on
      characteristics, kind, contact duration and clinical use of the device is
      cytotoxicity in vitro. This test defines the impact of the device on the cells
      through microscopic evaluation or through activities of the enzymes specific for
      living cells. Toxicity of the material to the cells may be reflected in: change
      of single cells or whole cell culture morphology, change of cellular metabolic
      activity, DNA damage or disadvantage of cell proliferation. Biocompatibility of
      the medical devices is one of the main elements considered in a risk management
      process at the stage of designing and manufacturing as well of the raw materials
      as the final product and the critical point in this matter is sterilization.

PMID- 29203753
TI  - [Definition and treatment of stroke over the centuries].
AB  - Stroke was already diagnosed in the ancient times. For hundreds of years the
      treatment of this disease has changed radically. According to the current WHO
      definition, stroke is a clinical syndrome caused by focal or generalized brain
      injury that lasts more than 24 hours or leads to death and has no other cause
      than vascular. Stroke constitutes a big social and economic problem, as it can
      lead to death or disability. In the highly developed countries stroke is the
      third most common cause of adult deaths, the second leading cause of dementia,
      and the most common cause of disability. The consequences of stroke also include
      epilepsy and depression. In the twentieth century, stroke was only treated
      symptomatically and rehabilitation was limited to passive exercises. The first
      breakthrough in ischemic stroke therapy was the introduction of aspirin (ASA),
      followed by intravenous thrombolysis using recombinant tissue plasminogen
      activator (rtPA), initially available in our country only in the drug programs,
      and since 2009 it has been reimbursed by the National Health Fund (NFZ).
      Gradually invasive stroke treatment has been developed. Mechanical thrombectomy
      is currently only performed in selected centers, giving hope for more effective
      stroke treatment. The purpose of this work was to show how stroke treatment has
      changed over the centuries.

PMID- 29203754
TI  - [Scientific research results commercialization as an opportunity for the
      physiotherapy development].
AB  - Physiotherapy is under the very intensive development. The research carried out
      around the world result in implementing new forms of therapy. For several years
      higher education institutions are trying to support scientists in an attempt to
      commercialize the results of research, although the process is complex. The
      practice in the world shows that the cooperation of science and business is
      possible and results in the implementation of modern solutions as real
      applications. It is important to scientists and people planning a career in
      science knew the rules and limitations of the above process.

PMID- 29203755
TI  - Churg-strauss syndrome: a case report.
AB  - A clinical case of Churg-Strauss syndrome has been reported on the 53-year-old
      female patient Ts. with bronchial asthma and allergic rhinitis. The main clinical
      signs and syndromes depending on the stage of the disease are presented, as well
      as therapeutic treatment of patients with this disease.

PMID- 29203756
TI  - 12 years of fighting liposarcoma: a case report.
AB  - The proportion of liposarcoma in the structure of cancer incidence is from 10 to
      35% of all mesenchymal tumors. This clinical observation describes an 12-year
      struggle with myxoid liposarcoma of the left upper arm, during which 17 surgeries
      were performed due to local recurrences, 17 radiation therapy courses and 5
      chemotherapy courses were conducted. Clinical observation shows the whole
      complexity of myxoid liposarcoma treatment. The effectiveness of therapeutic
      management is determined by persistent surgery, and also by the lack of
      expression of Pgp, glutathione-S-transferase, metallothionein and mutant p53 in
      tumor structure.

PMID- 29203757
TI  - Variant of myocardial infarction course in the patient with left ventricular non
      compaction.
AB  - Non-compacted left ventricle in adults is a rare occurrence, though it is
      diagnosed even more rarely. As a rule in patients with non-compacted left
      ventricle (LVNC) other pathologic condition is diagnosed, notably hypertrophic or
      dilated cardiomyopathy. The majority of LVNC cases are diagnosed in early infancy
      but currently there are asymptomatic cases detected by means of echocardiographic
      examination. Real prevalence of LVNC is unknown. According to many authors LVNC
      occurs in 9.2-9.5% of children with diagnosed cardiomyopathies. The majority of
      such children do not survive till adulthood because of progressive severe heart
      failure, fatal arrhythmias and thromboembolisms. This value ranges from 0.014 to
      0.05% in adult population. The article presents a clinical case illustrating the
      stages in establishing the diagnosis of non-compacted left ventricle in a young
      patient with myocardial infarction and congestive heart failure. Common
      characteristics of non-compacted left ventricle and connective tissue dysplasia
      syndrome in the patient suggested etiopathogenetic relationship between these two
      pathologic states. The basic common characteristic feature of both non-compacted
      left ventricle and connective tissue dysplasia syndrome proved to be multiple
      abnormal chords of the left ventricle. The patient was supposed to have some
      coronary circulation abnormality inherited together with non-compacted left
      ventricle and connective tissue dysplasia syndrome. Adverse prognosis and high
      mortality in non-compacted left ventricle require its early recognition and
      differentiated approach to treatment depending on the severity of the disease and
      using all modern methods of treatment both conservative and surgical.

PMID- 29203758
TI  - [Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (dipnech) - an
      overview of the cases diagnosed at the department of thoracic surgery in the
      years 2010-2014].
AB  - INTRODUCTION: Pulmonary neuroendocrine cells (PNEC) are present in the normal
      lungs with the incidence of 1 in 2500 epithelial cells. They usually proliferate
      in the presence of reactive processes related to inflammation and fibrosis of the
      lung parenchyma. The division of pulmonary neuroendocrine cell hyperplasia
      proposed by Travis et al. additionally distinguished diffuse idiopathic pulmonary
      neuroendocrine cell hyperplasia (DIPNECH) or proliferation that occurs in people
      without reactive hyperplasia risk factors. The confirmation of the DIPNECH
      diagnosis requires staining of biopsy specimens using the immunohistochemical
      technique for neuroendocrine markers. AIM: The aim of this study is to overview
      the cases of 5 patients in whom the histopathological DIPNECH diagnosis was made
      in the process of invasive diagnostics performed at the Department of Thoracic
      Surgery. The aim of the study is to evaluate typical clinical, functional,
      radiological and histopathological features of this rare disease syndrome.
      MATERIAL AND METHODS: In the period from April 2010 to June 2014, five patients
      with lesions in the lungs were subjected to invasive diagnostics.
      Histopathological and immunohistochemical examinations of the collected specimens
      were used to make the DIPNECH diagnosis in these patients. The natural history of
      the disease was traced based on a 5-year follow-up in one of the patients. In
      addition, we analyzed the literature with regard to the described cases.
      CONCLUSIONS: Thanks to the early diagnosis of non-specific lesions in the lungs,
      typical carcinoid which develops on the basis of discussed DIPNECH, was found in
      the resected material in two out of five operated patients. The accurate
      diagnosis of DIPNECH allows for the implementation of appropriate treatment and
      channels further management of the patient into the right direction.

PMID- 29203759
TI  - [Right hemicolectomy under spinal anesthesia due to cancer of ascending large
      bowel - case report].
AB  - Surgery procedures of the abdomen cavity are commonly performed in general
      anaesthesia. Patients from high risk group with circulatory insufficiency,
      respiratory failure pose a problem. They undergo surgical procedures for life
      indications and emergency cases. Regional anaesthesia can be an alternative for
      general anaesthesia, and makes planned surgical treatment possible for this group
      of patients. The study presents the case of 79-year-old male with chronic
      obstructive pulmonary disease, after left lung upper lobectomy, arterial
      hypertension, who underwent operation due to ascending large bowel cancer under
      spinal anaesthesia as planned.

PMID- 29203760
TI  - Developing a framework for evaluating the impact of Healthcare Improvement
      Science Education across Europe: a qualitative study.
AB  - PURPOSE: Frontline healthcare professionals are well positioned to improve the
      systems in which they work. Educational curricula, however, have not always
      equipped healthcare professionals with the skills or knowledge to implement and
      evaluate improvements. It is important to have a robust and standardized
      framework in order to evaluate the impact of such education in terms of
      improvement, both within and across European countries. The results of such
      evaluations will enhance the further development and delivery of healthcare
      improvement science (HIS) education. We aimed to describe the development and
      piloting of a framework for prospectively evaluating the impact of HIS education
      and learning. METHODS: The evaluation framework was designed collaboratively and
      piloted in 7 European countries following a qualitative methodology. The present
      study used mixed methods to gather data from students and educators. The
      framework took the Kirkpatrick model of evaluation as a theoretical reference.
      RESULTS: The framework was found to be feasible and acceptable for use across
      differing European higher education contexts according to the pilot study and the
      participants' consensus. It can be used effectively to evaluate and develop HIS
      education across European higher education institutions. CONCLUSION: We offer a
      new evaluation framework to capture the impact of HIS education. The
      implementation of this tool has the potential to facilitate the continuous
      development of HIS education.

PMID- 29203761
TI  - Pulmonary Vein Stenosis Following Single-Lung Transplantation Successfully
      Treated with Intravascular Ultrasound-Guided Angioplasty and Stent Placement.

PMID- 29203762
TI  - Emodin Impairs Radioresistance of Human Osteosarcoma Cells by Suppressing Sonic
      Hedgehog Signaling.

PMID- 29203763
TI  - Harnessing heterogeneous nucleation to control tin orientations in electronic
      interconnections.
AB  - While many aspects of electronics manufacturing are controlled with great
      precision, the nucleation of tin in solder joints is currently left to chance.
      This leads to a widely varying melt undercooling and different crystal
      orientations in each joint, which results in a different resistance to
      electromigration, thermomechanical fatigue, and other failure modes in each
      joint. Here we identify a family of nucleants for tin, prove their effectiveness
      using a novel droplet solidification technique, and demonstrate an approach to
      incorporate the nucleants into solder joints to control the orientation of the
      tin nucleation event. With this approach, it is possible to change tin nucleation
      from a stochastic to a deterministic process, and to generate single-crystal
      joints with their c-axis orientation tailored to best combat a selected failure
      mode.

PMID- 29203764
TI  - 3D genome of multiple myeloma reveals spatial genome disorganization associated
      with copy number variations.
AB  - The Hi-C method is widely used to study the functional roles of the three
      dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome
      sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple
      myeloma (MM) and how it associates with genomic variation and gene expression.
      Our results show that Hi-C interaction matrices are biased by copy number
      variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS
      data can improve the detection of translocations. We find that CNV breakpoints
      significantly overlap with topologically associating domain (TAD) boundaries.
      Compared to normal B cells, the numbers of TADs increases by 25% in MM, the
      average size of TADs is smaller, and about 20% of genomic regions switch their
      chromatin A/B compartment types. In summary, we report a 3D genome interaction
      map of aneuploid MM cells and reveal the relationship among CNVs, translocations,
      3D genome reorganization, and gene expression regulation.

PMID- 29203765
TI  - Internalization of a polysialic acid-binding Escherichia coli bacteriophage into
      eukaryotic neuroblastoma cells.
AB  - Eukaryotic organisms are continuously exposed to bacteriophages, which are
      efficient gene transfer agents in bacteria. However, bacteriophages are
      considered not to pass the eukaryotic cell membrane and enter nonphagocytic
      cells. Here we report the binding and penetration of Escherichia coli PK1A2
      bacteriophage into live eukaryotic neuroblastoma cells in vitro. The phage
      interacts with cell surface polysialic acid, which shares structural similarity
      with the bacterial phage receptor. Using fluorescence and electron microscopy, we
      show that phages are internalized via the endolysosomal route and persist inside
      the human cells up to one day without affecting cell viability. Phage capsid
      integrity is lost in lysosomes, and the phage DNA is eventually degraded. We did
      not detect the entry of phage DNA into the nucleus; however, we speculate that
      this might occur as a rare event, and propose that this potential mechanism could
      explain prokaryote-eukaryote gene flow.

PMID- 29203766
TI  - A new stem sarcopterygian illuminates patterns of character evolution in early
      bony fishes.
AB  - Discoveries of putative stem sarcopterygians from the late Silurian and Early
      Devonian of South China have increased our knowledge of the initial
      diversification of osteichthyans while also highlighting incongruities in
      character evolution in this major jawed vertebrate group. Character-rich
      endocrania are incompletely preserved for early bony fishes, limiting a detailed
      understanding of complex internal morphology and evolutionary changes in the
      cranium. Here we report a new sarcopterygian (Ptyctolepis brachynotus gen. et sp.
      nov.) from the Pragian (Early Devonian) of South China, which preserves a unique
      example of a completely ossified otoccipital division of the braincase in a stem
      lobe-finned fish. The hyomandibular facets are paired but lie dorsal to the
      jugular canal, representing a hitherto unobserved combination of derived and
      primitive character states. This new taxon prompts a reassessment of early
      osteichthyan interrelationships, including the phylogenetic placement of
      psarolepids, which might branch from the osteichthyan-rather than sarcopterygian
      stem.

PMID- 29203767
TI  - Crystal plasticity as an indicator of the viscous-brittle transition in magmas.
AB  - Understanding the flow of multi-phase (melt, crystals and bubbles) magmas is of
      great importance for interpreting eruption dynamics. Here we report the first
      observation of crystal plasticity, identified using electron backscatter
      diffraction, in plagioclase in andesite dome lavas from Volcan de Colima, Mexico.
      The same lavas, deformed experimentally at volcanic conduit temperature and load
      conditions, exhibit a further, systematic plastic response in the crystalline
      fraction, observable as a lattice misorientation. At higher stress, and higher
      crystal fraction, the amount of strain accommodated by crystal plasticity is
      larger. Crystal plastic distortion is highest in the intact segments of broken
      crystals, which have exceeded their plastic limit. We infer that crystal
      plasticity precludes failure and can punctuate the viscous-brittle transition in
      crystal-bearing magmas at certain shallow magmatic conditions. Since crystal
      plasticity varies systematically with imposed conditions, this raises the
      possibility that it may be used as a strain marker in well-constrained systems.

PMID- 29203768
TI  - Direct evidence of hidden local spin polarization in a centrosymmetric
      superconductor LaO0.55 F0.45BiS2.
AB  - Conventional Rashba spin polarization is caused by the combination of strong spin
      orbit interaction and spatial inversion asymmetry. However, Rashba-Dresselhaus
      type spin-split states are predicted in the centrosymmetric LaOBiS2 system by
      recent theory, which stem from the local inversion asymmetry of active BiS2
      layer. By performing high-resolution spin- and angle-resolved photoemission
      spectroscopy, we have investigated the electronic band structure and spin texture
      of superconductor LaO0.55F0.45BiS2. Here we present direct spectroscopic evidence
      for the local spin polarization of both the valence band and the conduction band.
      In particular, the coexistence of Rashba-like and Dresselhaus-like spin textures
      has been observed in the conduction band. The finding is of key importance for
      fabrication of proposed dual-gated spin-field effect transistor. Moreover, the
      spin-split band leads to a spin-momentum locking Fermi surface from which
      superconductivity emerges. Our demonstration not only expands the scope of
      spintronic materials but also enhances the understanding of spin-orbit
      interaction-related superconductivity.

PMID- 29203769
TI  - Three distinct developmental pathways for adaptive and two IFN-gamma-producing
      gammadelta T subsets in adult thymus.
AB  - Murine gammadelta T cells include subsets that are programmed for distinct
      effector functions during their development in the thymus. Under pathological
      conditions, different gammadelta T cell subsets can be protective or can
      exacerbate a disease. Here we show that CD117, CD200 and CD371, together with
      other markers, identify seven developmental stages of gammadelta T cells. These
      seven stages can be divided into three distinct developmental pathways that are
      enriched for different TCRdelta repertoires and exhibit characteristic expression
      patterns associated with adaptive (gammadeltaTn), IFN-gamma-producing
      (gammadeltaT1) and IFN-gamma/IL-4-co-producing gammadelta T cells
      (gammadeltaNKT). Developmental progression towards both IFN-gamma-producing
      subsets can be induced by TCR signalling, and each pathway results in thymic
      emigration at a different stage. Finally, we show that gammadeltaT1 cells are the
      predominating IFN-gamma-producing subset developing in the adult thymus. Thus,
      this study maps out three distinct development pathways that result in the
      programming of gammadeltaTn, gammadeltaT1 and gammadeltaNKT cells.

PMID- 29203770
TI  - The transcript cleavage factor paralogue TFS4 is a potent RNA polymerase
      inhibitor.
AB  - TFIIS-like transcript cleavage factors enhance the processivity and fidelity of
      archaeal and eukaryotic RNA polymerases. Sulfolobus solfataricus TFS1 functions
      as a bona fide cleavage factor, while the paralogous TFS4 evolved into a potent
      RNA polymerase inhibitor. TFS4 destabilises the TBP-TFB-RNAP pre-initiation
      complex and inhibits transcription initiation and elongation. All inhibitory
      activities are dependent on three lysine residues at the tip of the C-terminal
      zinc ribbon of TFS4; the inhibition likely involves an allosteric component and
      is mitigated by the basal transcription factor TFEalpha/beta. A chimeric variant
      of yeast TFIIS and TFS4 inhibits RNAPII transcription, suggesting that the
      molecular basis of inhibition is conserved between archaea and eukaryotes. TFS4
      expression in S. solfataricus is induced in response to infection with the S
      ulfolobus turreted icosahedral virus. Our results reveal a compelling functional
      diversification of cleavage factors in archaea, and provide novel insights into
      transcription inhibition in the context of the host-virus relationship.

PMID- 29203771
TI  - Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple
      myeloma.
AB  - Despite novel therapies, relapse of multiple myeloma (MM) is virtually
      inevitable. Amplification of chromosome 1q, which harbors the inflammation
      responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in
      30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine
      RNA editing has recently emerged as a driver of cancer progression, genomic
      amplification combined with inflammatory cytokine activation of ADAR1 could
      stimulate MM progression and therapeutic resistance. Here, we report that high
      ADAR1 RNA expression correlates with reduced patient survival rates in the MMRF
      CoMMpass data set. Expression of wild-type, but not mutant, ADAR1 enhances Alu
      dependent editing and transcriptional activity of GLI1, a Hedgehog (Hh) pathway
      transcriptional activator and self-renewal agonist, and promotes immunomodulatory
      drug resistance in vitro. Finally, ADAR1 knockdown reduces regeneration of high
      risk MM in serially transplantable patient-derived xenografts. These data
      demonstrate that ADAR1 promotes malignant regeneration of MM and if selectively
      inhibited may obviate progression and relapse.

PMID- 29203773
TI  - Temperature Dependence in Heterogeneous Nucleation with Application to the Direct
      Determination of Cluster Energy on Nearly Molecular Scale.
AB  - A re-examination of measurements of heterogeneous nucleation of water vapor on
      silver nanoparticles is presented here using a model-free framework that derives
      the energy of critical cluster formation directly from measurements of nucleation
      probability. Temperature dependence is correlated with cluster stabilization by
      the nanoparticle seed and previously found cases of unusual increasing nucleation
      onset saturation ratio with increasing temperature are explained. A necessary
      condition for the unusual positive temperature dependence is identified, namely
      that the critical cluster be more stable, on a per molecule basis, than the bulk
      liquid to exhibit the effect. Temperature dependence is next examined in the
      classical Fletcher model, modified here to make the energy of cluster formation
      explicit in the model.  The contact angle used in the Fletcher model is
      identified as the microscopic contact angle, which can be directly obtained from
      heterogeneous nucleation experimental data by a recently developed analysis
      method. Here an equivalent condition, increasing contact angle with temperature,
      is found necessary for occurrence of unusual temperature dependence. Our findings
      have immediate applications to atmospheric particle formation and nanoparticle
      detection in condensation particle counters (CPCs).

PMID- 29203774
TI  - Author Correction: Antagonistic evolution of an antibiotic and its molecular
      chaperone: how to maintain a vital ectosymbiosis in a highly fluctuating habitat.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has notbeen fixed in the paper..

PMID- 29203775
TI  - Glandular Morphometrics for Objective Grading of Colorectal Adenocarcinoma
      Histology Images.
AB  - Determining the grade of colon cancer from tissue slides is a routine part of the
      pathological analysis. In the case of colorectal adenocarcinoma (CRA), grading is
      partly determined by morphology and degree of formation of glandular structures.
      Achieving consistency between pathologists is difficult due to the subjective
      nature of grading assessment. An objective grading using computer algorithms will
      be more consistent, and will be able to analyse images in more detail. In this
      paper, we measure the shape of glands with a novel metric that we call the Best
      Alignment Metric (BAM). We show a strong correlation between a novel measure of
      glandular shape and grade of the tumour. We used shape specific parameters to
      perform a two-class classification of images into normal or cancerous tissue and
      a three-class classification into normal, low grade cancer, and high grade
      cancer. The task of detecting gland boundaries, which is a prerequisite of shape
      based analysis, was carried out using a deep convolutional neural network
      designed for segmentation of glandular structures. A support vector machine (SVM)
      classifier was trained using shape features derived from BAM. Through cross
      validation, we achieved an accuracy of 97% for the two-class and 91% for three
      class classification.

PMID- 29203772
TI  - Integrative transcriptomic analysis reveals key drivers of acute peanut allergic
      reactions.
AB  - Mechanisms driving acute food allergic reactions have not been fully
      characterized. We profile the dynamic transcriptome of acute peanut allergic
      reactions using serial peripheral blood samples obtained from 19 children before,
      during, and after randomized, double-blind, placebo-controlled oral challenges to
      peanut. We identify genes with changes in expression triggered by peanut, but not
      placebo, during acute peanut allergic reactions. Network analysis reveals that
      these genes comprise coexpression networks for acute-phase response and pro
      inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4,
      IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of
      coregulated networks in response to peanut. Leukocyte deconvolution analysis
      identifies changes in neutrophil, naive CD4+ T cell, and macrophage populations
      during peanut challenge. Analyses in 21 additional peanut allergic subjects
      replicate major findings. These results highlight key genes, biological
      processes, and cell types that can be targeted for mechanistic study and
      therapeutic targeting of peanut allergy.

PMID- 29203776
TI  - Non-Water-Suppressed 1H MR Spectroscopy with Orientational Prior Knowledge Shows
      Potential for Separating Intra- and Extramyocellular Lipid Signals in Human
      Myocardium.
AB  - Conditions such as type II diabetes are linked with elevated lipid levels in the
      heart, and significantly increased risk of heart failure; however, metabolic
      processes underlying the development of cardiac disease in type II diabetes are
      not fully understood. Here we present a non-invasive method for in vivo
      investigation of cardiac lipid metabolism: namely, IVS-McPRESS. This technique
      uses metabolite-cycled, non-water suppressed 1H cardiac magnetic resonance
      spectroscopy with prospective and retrospective motion correction. High-quality
      IVS-McPRESS data acquired from healthy volunteers allowed us to investigate the
      frequency shift of extramyocellular lipid signals, which depends on the
      myocardial fibre orientation. Assuming consistent voxel positioning relative to
      myofibres, the myofibre angle with the magnetic field was derived from the voxel
      orientation. For separation and individual analysis of intra- and
      extramyocellular lipid signals, the angle myocardial fibres in the spectroscopy
      voxel take with the magnetic field should be within +/-24.5 degrees . Metabolite
      and lipid concentrations were analysed with respect to BMI. Significant
      correlations between BMI and unsaturated fatty acids in intramyocellular lipids,
      and methylene groups in extramyocellular lipids were found. The proposed IVS
      McPRESS technique enables non-invasive investigation of cardiac lipid metabolism
      and may thus be a useful tool to study healthy and pathological conditions.

PMID- 29203777
TI  - Constraints from the dehydration of antigorite on high-conductivity anomalies in
      subduction zones.
AB  - Regions with high electrical conductivities in subduction zones have attracted a
      great deal of attention. Determining the exact origin of these anomalies could
      provide critical information about the water storage and cycling processes during
      subduction. Antigorite is the most important hydrous mineral within deep
      subduction zones. The dehydration of antigorite is believed to cause high
      conductivity anomalies. To date, the effects of dehydration on the electrical
      conductivity of antigorite remain poorly understood. Here, we report new
      measurements of the electrical conductivity of both natural and hot-pressed
      antigorite at pressures of 4 and 3 GPa, respectively, and at temperatures
      reaching 1073 K. We observed significantly enhanced conductivities when the
      antigorite was heated to temperatures beyond its thermodynamic stability field.
      Sharp increases in the electrical conductivity occurred at approximately 848 and
      898 K following the decomposition of antigorite to forsterite, enstatite and
      aqueous fluids. High electrical conductivities reaching 1 S/m can be explained by
      the presence of an interconnected network of conductive aqueous fluids. Based on
      these results for the electrical conductivity of antigorite, we conclude that
      high-conductivity regions associated with subduction zones can be attributed to
      dehydration-induced fluids and the formation of interconnected networks of
      aqueous fluids during the dehydration of antigorite.

PMID- 29203778
TI  - Kiwifruit R2R3-MYB transcription factors and contribution of the novel AcMYB75 to
      red kiwifruit anthocyanin biosynthesis.
AB  - Red kiwifruit (Actinidia chinensis) is a popular fresh fruit with a high market
      value due to its unique color, caused by anthocyanin accumulation. The R2R3-MYB
      transcription factors (TFs) have important roles in plant development and
      anthocyanin metabolism. In this first comprehensive study of R2R3-MYBs in
      kiwifruit, a total of 93 R2R3-MYB genes, including five novel previously
      unannotated AcMYBs, were identified. Their phylogenic relationship, exon-intron
      structures, and conserved motifs were analyzed. Based on transcriptome data, 60
      AcMYBs were expressed (FPKM > 1) across seven developmental stages of kiwifruit,
      revealing five expression patterns. One of the 5 newly identified R2R3 TFs,
      AcMYB75, showed an anthocyanin accumulation-linked expression pattern during
      fruit development. AcMYB75 localized to the nucleus and has an active
      transactivation domain, verifying it as a transcription factor. AcMYB75 protein
      specifically bound the promoter of the anthocyanin biosynthesis gene ANS in yeast
      one-hybrid system and in vivo. In 35 S:AcMYB75 Arabidopsis plants, anthocyanin
      significantly accumulated in leaves, and the expression of anthocyanin
      biosynthetic genes was greatly up-regulated. Together, these results suggest that
      AcMYB75 is involved in anthocyanin biosynthesis in kiwifruit. These findings will
      increase our understanding of AcMYBs involved in anthocyanin biosynthesis, and
      also benefit further functional characterization of R2R3-MYB genes in kiwifruit.

PMID- 29203779
TI  - Plasma channel undulator excited by high-order laser modes.
AB  - The possibility of utilizing plasma undulators and plasma accelerators to produce
      compact ultraviolet and X-ray sources, has attracted considerable interest for a
      few decades. This interest has been driven by the great potential to decrease the
      threshold for accessing such sources, which are mainly provided by a few
      dedicated large-scale synchrotron or free-electron laser (FEL) facilities.
      However, the broad radiation bandwidth of such plasma devices limits the source
      brightness and makes it difficult for the FEL instability to develop. Here, using
      multi-dimensional particle-in-cell (PIC) simulations, we demonstrate that a
      plasma undulator generated by the beating of a mixture of high-order laser modes
      propagating inside a plasma channel, leads to a few percent radiation bandwidth.
      The strength of the undulator can reach unity, the period can be less than a
      millimeter, and the number of undulator periods can be significantly increased by
      a phase locking technique based on the longitudinal tapering. Polarization
      control of such an undulator can be achieved by appropriately choosing the phase
      of the modes. According to our results, in the fully beam loaded regime, the
      electron current in the plasma undulator can reach 0.3 kA level, making such an
      undulator a potential candidate towards a table-top FEL.

PMID- 29203780
TI  - microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration
      and Comparative Analysis.
AB  - Breast cancer (BC) has a higher incidence in young Lebanese woman as compared to
      the West. We assessed the microRNA (miRNA) microarray profile of tissues derived
      from Lebanese patients with early BC and performed mRNA-miRNA integration
      analysis. 173 miRNAs were significantly dysregulated in 45 BC versus 17 normal
      adjacent breast tissues, including 74 with a fold change more than two of which
      17 were never reported before in cancer. Integration analysis of mRNA-miRNA
      microarray data revealed a potential role of 51 dysregulated miRNA regulating 719
      tumor suppressive or oncogenic mRNA associated with increased proliferation and
      decreased migration and invasion. We then performed a comparative miRNA
      microarray profile analysis of BC tissue between these 45 Lebanese and 197
      matched American BC patients. Notably, Lebanese BC patients had 21 exclusively
      dysregulated miRNA (e.g. miR-31, 362-3p, and 663) and 4 miRNA with different
      expression manner compared to American patients (e.g. miR-1288-star and 324-3p).
      Some of these differences could reflect variation in patient age at diagnosis or
      ethnic variation affecting miRNA epigenetic regulation or sequence of miRNA
      precursors. Our data provide a basis for genetic/epigenetic investigations to
      explore the role of miRNA in early stage BC in young women, including ethnic
      specific differences.

PMID- 29203781
TI  - A genomic perspective of the pink-headed duck Rhodonessa caryophyllacea suggests
      a long history of low effective population size.
AB  - The first molecular phylogenetic hypothesis for the possibly extinct pink-headed
      duck Rhodonessa caryophyllacea unambiguously shows that it belongs to the pochard
      radiation that also includes the genera Aythya and Netta. It is the sister to all
      modern-day pochards and belongs to a lineage that branched off from the others
      more than 2.8 million years ago. Rhodonessa caryophyllacea is believed to never
      have been common in modern time and we show this has probably been the situation
      for as long as 100,000 years. Our results suggest that their effective population
      size varied between 15,000 and 25,000 individuals during the last 150,000 years
      of the Pleistocene. The reasons behind this are largely unknown as very little is
      known about the life-history and biology of this species. Presumably it is due to
      factors related to feeding or to breeding, but we may never know this for sure.

PMID- 29203782
TI  - Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes.
AB  - Smoking is a major cause of respiratory conditions. To date, the genetic
      pleiotropy between smoking behavior and lung function/chronic obstructive
      pulmonary disease (COPD) have not been systematically explored. We leverage large
      data sets of smoking behavior, lung function and COPD, and addressed two
      questions, (1) whether the genetic predisposition of nicotine dependence
      influence COPD risk and lung function; and (2) the genetic pleiotropy follow
      causal or independent model. We found the genetic predisposition of nicotine
      dependence was associated with COPD risk, even after adjusting for smoking
      behavior, indicating genetic pleiotropy and independent model. Two known nicotine
      dependent loci (15q25.1 and 19q13.2) were associated with smoking adjusted lung
      function, and 15q25.1 reached genome-wide significance. At various suggestive p
      value thresholds, the smoking adjusted lung function traits share association
      signals with cigarettes per day and former smoking, substantially greater than
      random chance. Empirical data showed the genetic pleiotropy between nicotine
      dependence and COPD or lung function. The basis of pleiotropic effect is rather
      complex, attributable to a large number of genetic variants, and many variants
      functions through independent model, where the pleiotropic variants directly
      affect lung function, not mediated by influencing subjects' smoking behavior.

PMID- 29203783
TI  - Dietary amino acids and incidence of hypertension: A principle component analysis
      approach.
AB  - The current study aimed to investigate the association between dietary amino acid
      patterns and incidence of hypertension, using principal components factor
      analyses. This study was conducted within the framework of Tehran Lipid and
      Glucose Study on 4288 adults, who were free of hypertension at baseline (2008
      2011) and were followed for three years (2011-2014). Principal component factor
      analyses were conducted based on eight amino acid groups and three amino acid
      patterns were extracted. The first pattern was characterized by branched chain,
      aromatic, and alcoholic amino acids, and proline. Acidic amino acids and proline
      were highly loaded in the second pattern and the third was characterized by
      sulphuric and small amino acids. Adjusted odds ratio of the highest quartile of
      the first pattern was 1.83 (95%CI: 1.21-2.77, P for trend = 0.002) compared to
      the lowest one. The first pattern had high positive correlation with dietary
      intakes of animal protein and dairy, but was negatively correlated with plant
      protein, fruit, and vegetable. There was no significant association for the
      second and third patterns. Findings indicate that the dietary amino acid pattern,
      rich in branched chain, aromatic, and alcoholic amino acids, and proline could
      increase the risk of hypertension.

PMID- 29203784
TI  - Construction of a system using a deep learning algorithm to count cell numbers in
      nanoliter wells for viable single-cell experiments.
AB  - For single-cell experiments, it is important to accurately count the number of
      viable cells in a nanoliter well. We used a deep learning-based convolutional
      neural network (CNN) on a large amount of digital data obtained as microscopic
      images. The training set consisted of 103 019 samples, each representing a
      microscopic grayscale image. After extensive training, the CNN was able to
      classify the samples into four categories, i.e., 0, 1, 2, and more than 2 cells
      per well, with an accuracy of 98.3% when compared to determination by two trained
      technicians. By analyzing the samples for which judgments were discordant, we
      found that the judgment by technicians was relatively correct although cell
      counting was often difficult by the images of discordant samples. Based on the
      results, the system was further enhanced by introducing a new algorithm in which
      the highest outputs from CNN were used, increasing the accuracy to higher than
      99%. Our system was able to classify the data even from wells with a different
      shape. No other tested machine learning algorithm showed a performance higher
      than that of our system. The presented CNN system is expected to be useful for
      various single-cell experiments, and for high-throughput and high-content
      screening.

PMID- 29203785
TI  - Key site residues of pheromone-binding protein 1 involved in interacting with sex
      pheromone components of Helicoverpa armigera.
AB  - Pheromone binding proteins (PBPs) are widely distributed in insect antennae, and
      play important roles in the perception of sex pheromones. However, the detail
      mechanism of interaction between PBPs and odorants remains in a black box. Here,
      a predicted 3D structure of PBP1 of the serious agricultural pest, Helicoverpa
      armigera (HarmPBP1) was constructed, and the key residues that contribute to
      binding with the major sex pheromone components of this pest, (Z)-11- hexadecenal
      (Z11-16:Ald) and (Z)-9- hexadecenal (Z9-16:Ald), were predicted by molecular
      docking. The results of molecular simulation suggest that hydrophobic
      interactions are the main linkage between HarmPBP1 and the two aldehydes, and
      four residues in the binding pocket (Phe12, Phe36, Trp37, and Phe119) may
      participate in binding with these two ligands. Then site-directed mutagenesis and
      fluorescence binding assays were performed, and significant decrease of the
      binding ability to both Z11-16:Ald and Z9-16:Ald was observed in three mutants of
      HarmPBP1 (F12A, W37A, and F119A). These results revealed that Phe12, Trp37, and
      Phe119 are the key residues of HarmPBP1 in binding with the Z11-16:Ald and Z9
      16:Ald. This study provides new insights into the interactions between pheromone
      and PBP, and may serve as a foundation for better understanding of the pheromone
      recognition in moths.

PMID- 29203786
TI  - Antigen-specific oncolytic MV-based tumor vaccines through presentation of
      selected tumor-associated antigens on infected cells or virus-like particles.
AB  - Recombinant vaccine strain-derived measles virus (MV) is clinically tested both
      as vaccine platform to protect against other pathogens and as oncolytic virus for
      tumor treatment. To investigate the potential synergism in anti-tumoral efficacy
      of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor
      antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity,
      both antigens were presented by retroviral virus-like particle produced in situ
      during MV-infection. All recombinant MV revealed normal growths, genetic
      stability, and proper expression and presentation of both antigens. Potent
      antigen-specific humoral and cellular immunity were found in immunized MV
      susceptible IFNAR-/--CD46Ge mice. These immune responses significantly inhibited
      metastasis formation or increased therapeutic efficacy compared to control MV in
      respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine
      melanoma cells. These data indicate the potential of MV to trigger selected tumor
      antigen-specific immune responses on top of direct tumor lysis for enhanced
      efficacy.

PMID- 29203788
TI  - Highly-Sensitive Thin Film THz Detector Based on Edge Metal-Semiconductor-Metal
      Junction.
AB  - Terahertz (THz) detectors have been extensively studied for various applications
      such as security, wireless communication, and medical imaging. In case of metal
      insulator-metal (MIM) tunnel junction THz detector, a small junction area is
      desirable because the detector response time can be shortened by reducing it. An
      edge metal-semiconductor-metal (EMSM) junction has been developed with a small
      junction area controlled precisely by the thicknesses of metal and semiconductor
      films. The voltage response of the EMSM THz detector shows the clear dependence
      on the polarization angle of incident THz wave and the responsivity is found to
      be very high (~2,169 V/W) at 0.4 THz without any antenna and signal amplifier.
      The EMSM junction structure can be a new and efficient way of fabricating the
      nonlinear device THz detector with high cut-off frequency relying on extremely
      small junction area.

PMID- 29203787
TI  - CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting
      Brca1, Pten and Nf1, and correlation with platinum sensitivity.
AB  - Transplantable murine models of ovarian high grade serous carcinoma (HGSC) remain
      an important research tool. We previously showed that ID8, a widely-used
      syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC,
      and used CRISPR/Cas9 gene editing to generate derivatives with deletions in Trp53
      and Brca2. Here we have used one ID8 Trp53 -/- clone to generate further mutants,
      with additional mutations in Brca1, Pten and Nf1, all of which are frequently
      mutated or deleted in HGSC. We have also generated clones with triple deletions
      in Trp53, Brca2 and Pten. We show that ID8 Trp53 -/-;Brca1 -/- and Trp53 -/
      ;Brca2 -/- cells have defective homologous recombination and increased
      sensitivity to both platinum and PARP inhibitor chemotherapy compared to Trp53 -/
      . By contrast, loss of Pten or Nf1 increases growth rate in vivo, and reduces
      survival following cisplatin chemotherapy in vivo. Finally, we have also targeted
      Trp53 in cells isolated from a previous transgenic murine fallopian tube
      carcinoma model, and confirmed that loss of p53 expression in this second model
      accelerates intraperitoneal growth. Together, these CRISPR-generated models
      represent a new and simple tool to investigate the biology of HGSC, and the ID8
      cell lines are freely available to researchers.

PMID- 29203789
TI  - Prevalence of malaria in two highly endemic Community Health Centers in the
      Bastar district, Chhattisgarh showing mixed infections with Plasmodium species.
AB  - Malaria is a major public health problem in India and in the Chhattisgarh state.
      The diagnosis of malaria presents a major challenge in remote areas The
      prevalence of malaria in Darbha and Kilepal Community Health Centers (CHCs) of
      the Jagdalpur district, Chhattisgarh affected by conflict was determined using
      microscopy and polymerase chain reaction (PCR). In the year 2015, 29.4% and 21.5%
      cases were found to be positive for malaria at the Darbha and Kilepal CHCs,
      respectively, by microscopy, and 7.4% and 1.6% of cases had mixed infections,
      respectively. Among the suspected cases of mixed infections and doubtful
      diagnoses, 21% had mixed infections with two or more species at the Darbha CHC,
      and 17% from the Kilepal CHC, as determined by PCR. Both the P. vivax subspecies
      Pv210 (56%) and Pv247 (44%) and the P. ovale curtisi subspecies were found in
      this area. The high proportion of mixed malaria parasitic infections detected in
      this study indicate the need to adequately train health staff involved in
      diagnosing malaria. This study showed that there is a need for site-specific data
      to understand the epidemiological picture and to develop appropriate intervention
      strategies and management guidelines for controlling and eliminating malaria in
      India.

PMID- 29203790
TI  - Author Correction: How visual experience impacts the internal and external
      spatial mapping of sensorimotor functions.
AB  - A correction has been published and is appended to both the HTML and PDF versions
      of this paper. The error has been fixed in the paper.

PMID- 29203791
TI  - Identification of insulin-sensitizing molecules acting by disrupting the
      interaction between the Insulin Receptor and Grb14.
AB  - Metabolic diseases are characterized by a decreased action of insulin. During the
      course of the disease, usual treatments frequently fail and patients are finally
      submitted to insulinotherapy. There is thus a need for innovative therapeutic
      strategies to improve insulin action. Growth factor receptor-bound protein 14
      (Grb14) is a molecular adapter that specifically binds to the activated insulin
      receptor (IR) and inhibits its tyrosine kinase activity. Molecules disrupting
      Grb14-IR binding are therefore potential insulin-sensitizing agents. We used
      Structure-Based Virtual Ligand Screening to generate a list of 1000 molecules
      predicted to hinder Grb14-IR binding. Using an acellular bioluminescence
      resonance energy transfer (BRET) assay, we identified, out of these 1000
      molecules, 3 compounds that inhibited Grb14-IR interaction. Their inhibitory
      effect on insulin-induced Grb14-IR interaction was confirmed in co
      immunoprecipitation experiments. The more efficient molecule (C8) was further
      characterized. C8 increased downstream Ras-Raf and PI3-kinase insulin signaling,
      as shown by BRET experiments in living cells. Moreover, C8 regulated the
      expression of insulin target genes in mouse primary hepatocytes. These results
      indicate that C8, by reducing Grb14-IR interaction, increases insulin signalling.
      The use of C8 as a lead compound should allow for the development of new
      molecules of potential therapeutic interest for the treatment of diabetes.

PMID- 29203792
TI  - Uncovering the Pharmacological Mechanism of Astragalus Salvia Compound on
      Pregnancy-Induced Hypertension Syndrome by a Network Pharmacology Approach.
AB  - To uncover the pharmacological mechanism of Astragalus Salvia compound (ASC) on
      pregnancy-induced hypertension syndrome (PIH), to provide useful information for
      clinical, as well as to connect the basic and clinical by a network
      pharmacological approach, we used network pharmacological approach. We collected
      ASC's compounds by traditional Chinese Medicine databases, and input them into
      PharmMapper to got their targets. Then we acquired PIH targets from Genecards and
      OMIM, collected the interactions of all the targets and other human proteins via
      String and INACT. We also constructed the network by Cytoscape and analyze it by
      MCODE so as to get clusters. Finally, we put all the targets of clusters into
      DAVID to do GO enrichment analysis. After these, four networks are constructed by
      Cytoscape; they are PIH network, compound-compound target network of ASC, ASC-PIH
      network, and compound target-PIH target-other human proteins' PPI network.
      According to the results, we think that ASC may directly regulate several
      biological processes and their genes in "endothelial cell activation and injury"
      and "placental or trophoblast cell ischemia" models to treat PIH. And it may
      indirectly act on the rest of the biological process to treat PIH or may not.

PMID- 29203793
TI  - Environmental DNA reveals tropical shark diversity in contrasting levels of
      anthropogenic impact.
AB  - Sharks are charismatic predators that play a key role in most marine food webs.
      Their demonstrated vulnerability to exploitation has recently turned them into
      flagship species in ocean conservation. Yet, the assessment and monitoring of the
      distribution and abundance of such mobile species in marine environments remain
      challenging, often invasive and resource-intensive. Here we pilot a novel, rapid
      and non-invasive environmental DNA (eDNA) metabarcoding approach specifically
      targeted to infer shark presence, diversity and eDNA read abundance in tropical
      habitats. We identified at least 21 shark species, from both Caribbean and
      Pacific Coral Sea water samples, whose geographical patterns of diversity and
      read abundance coincide with geographical differences in levels of anthropogenic
      pressure and conservation effort. We demonstrate that eDNA metabarcoding can be
      effectively employed to study shark diversity. Further developments in this field
      have the potential to drastically enhance our ability to assess and monitor
      elusive oceanic predators, and lead to improved conservation strategies.

PMID- 29203794
TI  - Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination
      development.
AB  - We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine.
      Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein
      (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We
      have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates
      behavioral deficits that are not rescued by single NAA supplementation, although
      the reason for which is still not clarified. It is possible that the
      developmental impairment results from deletion of SHATI/NAT8L in the mouse brain,
      because NAA is involved in myelination through lipid synthesis in
      oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in
      brain development. In this study, we found that the expression of Shati/Nat8l
      mRNA was increased with brain development in mice, while there was a reduction in
      the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but
      not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces
      several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment
      ameliorates the behavioral impairments and normalizes the reduced protein level
      of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is
      involved in myelination in the juvenile mouse brain via supplementation of
      acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental
      neuronal dysfunction.

PMID- 29203795
TI  - Water depth affects reproductive allocation and reproductive allometry in the
      submerged macrophyte Vallisneria natans.
AB  - In freshwater ecosystems, shifts in hydrological regimes have profound effects on
      reproductive output (R), along with vegetative biomass (V) and survival of
      plants. Because reproductive allocation (RA) is allometric, it remains unclear
      whether the observed variation of RA in response to water level variability is
      due to fixed patterns of development or plasticity in the developmental
      trajectories. Here, we investigated shifts in RA of a submerged macrophyte
      Vallisneria natans in response to water depth to test the hypothesis that
      allometric trajectories of RA are highly plastic. Plants were grown at three
      water depths (50, 100 and 150 cm) and measured after 26 weeks of growth. The
      relationships between R and V among treatments were compared. Deep water affected
      both biomass and number of fruits produced per plant, leading to less sexual
      reproduction. Plants in deep water started flowering at a smaller size and
      despite their small mature size, had a relatively high RA. Furthermore, these
      plants had a much lower log R-log V relationship than shallow- or intermediate
      water plants. In conclusion, reproduction of V. natans is highly variable across
      water depth treatments, and variations in reproductive allometry represent
      different strategies under an important stress gradient for these freshwater
      angiosperms.

PMID- 29203797
TI  - The interfacial nature of proximity-induced magnetism and the Dzyaloshinskii
      Moriya interaction at the Pt/Co interface.
AB  - The Dzyaloshinskii-Moriya interaction has been shown to stabilise Neel domain
      walls in magnetic thin films, allowing high domain wall velocities driven by spin
      current effects. The interfacial Dzyaloshinskii-Moriya interaction (IDMI) occurs
      at the interface between ferromagnetic and heavy metal layers with strong spin
      orbit coupling, but details of the interaction remain to be understood and the
      role of proximity induced magnetism (PIM) in the heavy metal is unknown. Here
      IDMI and PIM are reported in Pt determined as a function of Au and Ir spacer
      layers in Pt/Co/Au,Ir/Pt. Both interactions are found to be sensitive to sub
      nanometre changes in the spacer thickness, correlating over sub-monolayer spacer
      thicknesses, but not for thicker spacers where IDMI continues to change even
      after PIM is lost.

PMID- 29203798
TI  - Relevance of MIC-1 in the Era of PSA as a Serum Based Predictor of Prostate
      Cancer: A Critical Evaluation.
AB  - To reduce the ambiguity of contradictory observations in different studies
      regarding the expression level of Macrophage Inhibitory Cytokine-1 (MIC-1) in
      serum in prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy
      controls (HC), we designed this double-blind study. The study comprises 240 sera
      from PC, BPH and HC subjects. The expression level of MIC-1 in PC, BPH and HC
      were appraised using Western blot (WB) and ELISA based approach. WB and ELISA
      appraisal reveals that the expression level of MIC-1 is significantly higher in
      PC than in HC or BPH subjects. Regression analysis revealed a significant
      correlation between MIC-1 vs. PSA (r = 0.09; p < 0.001) and MIC-1 vs. GS (r =
      0.7; p < 0.001). ROC analysis using discriminant predicted probability revealed
      that the MIC-1 was better than PSA. Moreover, the combination of MIC-1 and PSA
      was allowing 99.1% AUC for the differentiation of BPH + PC from HC, 97.9% AUC for
      differentiation of BPH from HC, 98.6% AUC for differentiation of PC from HC, and
      96.7% AUC for the differentiation of PC from BPH. The augmented expression of MIC
      1 in PC compared to BPH and HC subjects is in concurrent of the over-expression
      of MIC-1 in PC reports and confiscates the contradictory findings of other
      studies.

PMID- 29203796
TI  - Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse
      model of Down syndrome.
AB  - Down syndrome (DS) is caused by the triplication of human chromosome 21 and
      represents the most frequent genetic cause of intellectual disability. The
      trisomic Ts65Dn mouse model of DS shows synaptic deficits and reproduces the
      essential cognitive disabilities of the human syndrome. Aerobic exercise improved
      various neurophysiological dysfunctions in Ts65Dn mice, including hippocampal
      synaptic deficits, by promoting synaptogenesis and neurotransmission at
      glutamatergic terminals. Most importantly, the same intervention also prompted
      the recovery of hippocampal adult neurogenesis and synaptic plasticity and
      restored cognitive performance in trisomic mice. Additionally, the expression of
      brain-derived neurotrophic factor (BDNF) was markedly decreased in the
      hippocampus of patients with DS. Since the positive effect of exercise was
      paralleled by increased BDNF expression in trisomic mice, we investigated the
      effectiveness of a BDNF-mimetic treatment with 7,8-dihydroxyflavone at
      alleviating intellectual disabilities in the DS model. Pharmacological
      stimulation of BDNF signaling rescued synaptic plasticity and memory deficits in
      Ts65Dn mice. Based on our findings, Ts65Dn mice benefit from interventions aimed
      at promoting brain plasticity, and we provide evidence that BDNF signaling
      represents a potentially new pharmacological target for treatments aimed at
      rescuing cognitive disabilities in patients with DS.

PMID- 29203799
TI  - Essential involvement of the CX3CL1-CX3CR1 axis in bleomycin-induced pulmonary
      fibrosis via regulation of fibrocyte and M2 macrophage migration.
AB  - The potential role of macrophages in pulmonary fibrosis (PF) prompted us to
      evaluate the roles of CX3CR1, a chemokine receptor abundantly expressed in
      macrophages during bleomycin (BLM)-induced PF. Intratracheal BLM injection
      induced infiltration of leukocytes such as macrophages into the lungs, which
      eventually resulted in fibrosis. CX3CR1 expression was mainly detected in the
      majority of macrophages and in a small portion of alpha-smooth muscle actin
      positive cells in the lungs, while CX3CL1 was expressed in macrophages. BLM
      induced fibrotic changes in the lungs were reduced without any changes in the
      number of leukocytes in Cx3cr1 -/- mice, as compared with those in the wild-type
      (WT) mice. However, intrapulmonary CX3CR1+ macrophages displayed pro-fibrotic M2
      phenotypes; lack of CX3CR1 skewed their phenotypes toward M1 in BLM-challenged
      lungs. Moreover, fibrocytes expressed CX3CR1, and were increased in BLM
      challenged WT lungs. The number of intrapulmonary fibrocytes was decreased in
      Cx3cr1 -/- mice. Thus, locally-produced CX3CL1 can promote PF development
      primarily by attracting CX3CR1-expressing M2 macrophages and fibrocytes into the
      lungs.

PMID- 29203800
TI  - Cortical organization restored by cochlear implantation in young children with
      single sided deafness.
AB  - Early treatment of single sided deafness in children has been recommended to
      protect from neurodevelopmental preference for the better hearing ear and from
      social and educational deficits. A fairly homogeneous group of five young
      children (<=3.6 years of age) with normal right sided hearing who received a
      cochlear implant to treat deafness in their left ears were studied. Etiology of
      deafness was largely cytomegalovirus (n = 4); one child had an enlarged
      vestibular aqueduct. Multi-channel electroencephalography of cortical evoked
      activity was measured repeatedly over time at: 1) acute (0.5 +/- 0.7 weeks); 2)
      early chronic (1.1 +/- 0.2 months); and 3) chronic (5.8 +/- 3.4 months) cochlear
      implant stimulation. Results indicated consistent responses from the normal right
      ear with marked changes in activity from the implanted left ear. Atypical
      distribution of peak amplitude activity from the implanted ear at acute
      stimulation marked abnormal lateralization of activity to the ipsilateral left
      auditory cortex and recruitment of extra-temporal areas including left frontal
      cortex. These abnormalities resolved with chronic implant use and contralateral
      aural preference emerged in both auditory cortices. These findings indicate that
      early implantation in young children with single sided deafness can rapidly
      restore bilateral auditory input to the cortex needed to improve binaural
      hearing.

PMID- 29203801
TI  - De novo design of RNA-binding proteins with a prion-like domain related to
      ALS/FTD proteinopathies.
AB  - Aberrant RNA-binding proteins form the core of the neurodegeneration cascade in
      spectrums of disease, such as amyotrophic lateral sclerosis (ALS)/frontotemporal
      dementia (FTD). Six ALS-related molecules, TDP-43, FUS, TAF15, EWSR1,
      heterogeneous nuclear (hn)RNPA1 and hnRNPA2 are RNA-binding proteins containing
      candidate mutations identified in ALS patients and those share several common
      features, including harboring an aggregation-prone prion-like domain (PrLD)
      containing a glycine/serine-tyrosine-glycine/serine (G/S-Y-G/S)-motif-enriched
      low-complexity sequence and rich in glutamine and/or asparagine. Additinally,
      these six molecules are components of RNA granules involved in RNA quality
      control and become mislocated from the nucleus to form cytoplasmic inclusion
      bodies (IBs) in the ALS/FTD-affected brain. To reveal the essential mechanisms
      involved in ALS/FTD-related cytotoxicity associated with RNA-binding proteins
      containing PrLDs, we designed artificial RNA-binding proteins harboring G/S-Y-G/S
      motif repeats with and without enriched glutamine residues and nuclear
      import/export-signal sequences and examined their cytotoxicity in vitro. These
      proteins recapitulated features of ALS-linked molecules, including insoluble
      aggregation, formation of cytoplasmic IBs and components of RNA granules, and
      cytotoxicity instigation. These findings indicated that these artificial RNA
      binding proteins mimicked features of ALS-linked molecules and allowed the study
      of mechanisms associated with gain of toxic functions related to ALS/FTD
      pathogenesis.

PMID- 29203802
TI  - Cooling-rate induced softening in a colloidal glass.
AB  - Contrary to crystalline solids, amorphous solids always become softer when
      vitrifying the melts under higher cooling rates. Understanding this phenomenon is
      of utmost importance in providing a basis for the mechanical-performance control
      of amorphous solids. However, the underlying mechanisms leading to this cooling
      rate-induced softening of amorphous solids have remained elusive, especially the
      dynamic reasons are neglected. Here, we use a colloidal glass as the model system
      to directly study this issue. Shear modulus is used as the representative
      parameter to monitor the stress-bearing properties of colloidal glass. The space
      spanning immobile particles, whose population is sensitive to the cooling rate,
      are found to make the dominant contribution to the shear modulus. The rapid
      solidification induced softening of colloidal glass is observed to originate from
      fewer immobile particles formed at higher cooling rates.

PMID- 29203803
TI  - Brain Structural Bases of Tendency to Forgive: evidence from a young adults
      sample using voxel-based morphometry.
AB  - Tendency to forgive refers to one's global dispositional level of forgiveness
      across situations and relationships. Brain imaging studies examined activation
      patterns underlying forgiving response, yet focal differences in brain structures
      related to tendency to forgive have never been investigated. In this study, voxel
      based morphometry was used to investigate relations between gray matter/white
      matter volume (GMV/WMV) and individual differences in tendency to forgive in a
      large young sample. Participants were 199 young students (60 men) who completed
      the tendency to forgive scale (TTF) and underwent an anatomical magnetic
      resonance imaging scan. Results showed that higher TTF scores were associated
      with larger GMV in the regions of dorsolateral prefrontal cortex, and smaller GMV
      in the regions of the right insular cortex and inferior frontal gyrus (IFG).
      Moreover, higher TTF scores were also related to smaller WMV in the regions of
      the left IFG. Together, these findings suggest structural variations for
      individual differences in the tendency to forgive, distributed across different
      brain regions associated with empathic response and cognitive control.

PMID- 29203804
TI  - KIF1Bbeta increases ROS to mediate apoptosis and reinforces its protein
      expression through O 2- in a positive feedback mechanism in neuroblastoma.
AB  - Relapse-prone, poor prognosis neuroblastoma is frequently characterized by
      deletion of chr1p36 where tumor suppressor gene KIF1Bbeta resides. Interestingly,
      many 1p36-positive patients failed to express KIF1Bbeta protein. Since altered
      cellular redox status has been reported to be involved in cell death and protein
      modification, we investigated the relationship between reactive oxygen species
      (ROS) and KIF1Bbeta. Here, we showed that wild-type KIF1Bbeta protein expression
      positively correlates with superoxide (O2-) and total ROS levels in neuroblastoma
      cells, unlike apoptotic loss-of-function KIF1Bbeta mutants. Overexpression of
      KIF1Bbeta apoptotic domain variants increases total ROS and, specifically O2-,
      whereas knockdown of endogenous KIF1Bbeta decreases ROS and O2-. Interestingly,
      O2- increases KIF1Bbeta protein expression, independent of the proteasomal
      degradation pathway. Scavenging O2- or ROS decreases KIF1Bbeta protein expression
      and subsequent apoptosis. Moreover, treatment with investigational redox compound
      Gliotoxin increases O2-, KIF1Bbeta protein expression, apoptosis and colony
      formation inhibition. Overall, our findings suggest that ROS and O2- may be
      important downstream effectors of KIF1Bbeta-mediated apoptosis. Subsequently, O2-
      produced may increase KIF1Bbeta protein expression in a positive feedback
      mechanism. Therefore, ROS and, specifically O2-, may be critical regulators of
      KIF1Bbeta-mediated apoptosis and its protein expression in neuroblastoma.

PMID- 29203805
TI  - A novel paradigm to study interpersonal threat-related learning and extinction in
      children using virtual reality.
AB  - Disruptions in fear-extinction learning are centrally implicated in a range of
      stress-related disorders, including anxiety and posttraumatic stress disorder.
      Given that these disorders frequently begin in childhood/adolescence, an
      understanding of fear-extinction learning in children is essential for (1)
      detecting the source of developmental susceptibility, (2) identifying mechanisms
      leading to pathology, and (3) informing the development and/or more judicious
      application of treatments for youth. Here, we offer and validate a novel virtual
      reality paradigm to study threat-related learning and extinction in children that
      models real-world cues, environments, and fear-inducing events that children are
      likely to experience, and are linked to the development of fear- and stress
      related pathologies. We found that our paradigm is well tolerated in children as
      young as 6 years, that children show intact fear and extinction learning, and
      show evidence of divergence in subjective, physiological, and behavioral measures
      of conditioned fear. The paradigm is available for use in 3-D and in 2-D (e.g.,
      for the MRI scanner) upon request at www.tnp2lab.org .

PMID- 29203806
TI  - Reduced cell size, chromosomal aberration and altered proliferation rates are
      characteristics and confounding factors in the STHdh cell model of Huntington
      disease.
AB  - Huntington disease is a fatal neurodegenerative disorder caused by a CAG repeat
      expansion in the gene encoding the huntingtin protein. Expression of the mutant
      protein disrupts various intracellular pathways and impairs overall cell
      function. In particular striatal neurons seem to be most vulnerable to mutant
      huntingtin-related changes. A well-known and commonly used model to study
      molecular aspects of Huntington disease are the striatum-derived STHdh cell lines
      generated from wild type and huntingtin knock-in mouse embryos. However, obvious
      morphological differences between wild type and mutant cell lines exist, which
      have rarely been described and might not have always been considered when
      designing experiments or interpreting results. Here, we demonstrate that STHdh
      cell lines display differences in cell size, proliferation rate and chromosomal
      content. While the chromosomal divergence is considered to be a result of the
      cells' tumour characteristics, differences in size and proliferation, however,
      were confirmed in a second non-immortalized Huntington disease cell model.
      Importantly, our results further suggest that the reported phenotypes can
      confound other study outcomes and lead to false conclusions. Thus, careful
      experimental design and data analysis are advised when using these cell models.

PMID- 29203807
TI  - Mitochondrial genomic variation and phylogenetic relationships of three groups in
      the genus Scaphoideus (Hemiptera: Cicadellidae: Deltocephalinae).
AB  - The widespread leafhopper genus Scaphoideus Uhler is the most diverse genus in
      Scaphoideini and includes some species that are serious pests and vectors of
      plant pathogens. Here the first Scaphoideus mitogenome sequences are provided for
      three species, S. maai, S. nigrivalveus and S. varius, representing three main
      species groups in the Oriental region based on color pattern. The lengths of
      these three mitogenomes were 15,188, 15,235 and 15,207 bp, respectively. Gene
      order of three mitogenomes is highly conserved and identical to that of the
      putative ancestral insect. All three mitogenomes exhibited similar AT nucleotide
      bias, AT-, GC-skews and codon usage. One large 101 bp intergenic spacer between
      trnY and cox1 was in S. varius. All 22 tRNA genes had typical cloverleaf
      secondary structures, except for trnS1 (AGN) which appears to lack the
      dihydrouridine arm. Genes atp8, nad6 and nad2 were highly variable while cox1
      showed the lowest nucleotide diversity. Phylogenetic analyses of three
      concatenated nucleotide datasets using maximum likelihood and Bayesian methods,
      comprising all 13 mitogenomes currently available for Membracoidea plus
      mitogenomes for eight outgroup species representing other cicadomorphan
      superfamilies, yielded the same topology in which Scaphoideus species formed a
      monophyletic group within a larger clade comprising three other included
      Deltocephalinae.

PMID- 29203808
TI  - Association between smoking and the peripheral vestibular disorder: a
      retrospective cohort study.
AB  - Common inner ear diseases include peripheral vestibular disorder (PVD) and
      hearing impairment. The association between smoking and peripheral vestibular
      disorder (PVD) is unclear. We examined associations between smoking and new PVD
      events. In this retrospective study, we consecutively enrolled 393 participants
      aged >=20 years [mean age 65.3 years; males 133 (33.8%)] treated for
      hypertension, dyslipidaemia, or diabetes mellitus at a primary care clinic
      between November 2011 and March 2013. Participants were categorized as ever
      smokers (including current and past -smokers; divided per <30 and >=30 pack
      years), and never-smokers. New PVD events were reported over a 1-year follow-up
      period. Hazard ratios (HR) for new onset PVD were estimated using the Cox
      proportional hazard regression model. Compared to never-smokers, the adjusted HR
      was 2.22 for ever-smokers and 2.70 for all ever-smokers with >=30 pack-years
      among all 393 participants. Among male participants, compared to never-smokers,
      the adjusted HR was 4.41 for ever-smokers with >=30 pack-years. A smoking history
      of >=30 pack-years was strongly associated with the risk of new onset PVD in
      males but not, females. This study may assist patients with smoking cessation for
      the prevention of new PVD events among males.

PMID- 29203809
TI  - Femtosecond-Resolved Excited State Relaxation Dynamics of Copper (II)
      Tetraphenylporphyrin (CuTPP) After Soret Band Excitation.
AB  - Excited state relaxation dynamics of Copper (II) tetraphenylporphyrin (CuTPP)
      after Soret band excitation have been investigated in various solvents by
      femtosecond broadband transient absorption spectroscopy. Significant role of
      charge transfer state has been confirmed from fast relaxation of triplet CuTPP in
      pyridine, giving tau ~ 26.5 ps. In piperidine, the transient measured at 480 nm
      shows biexponential behavior with distinct time constants of 300 fs and 27.4 ps.
      The fast component with tau ~ 300 fs is attributed to relaxation of the CuTPP
      piperidine adduct populated in the ground state, giving the intrinsic relaxation
      rate of the CuTPP exciplex for the first time. For CuTPP in O-coordinating
      solvents of 1,4-dioxane and tetrahydrofuran (THF), a completely new relaxation
      channel via the 2[dz2, dx2-y2] state is opened. As the exciplex formation is
      diffusion controlled, triplet CuTPP lifetimes in pure solvents employed here are
      all measured to be more or less same to give ~30 ps, whereas the 2[dz2, dx2-y2]
      exciplex formed by the ligation with O-coordinating solvents is found to relax
      much slowly to the ground state, giving lifetimes of ~360 and ~270 ps in 1,4
      dioxane and THF, respectively.

PMID- 29203810
TI  - Effective litmus gene test for monitoring the quality of blood samples:
      Application to Alzheimer's disease diagnostics.
AB  - Gene expression profiles reflect the biologically diverse activities of cells
      under specific cell environments. Using the transcriptional response of cultured
      cells to blood composition, we developed a litmus gene assay to discriminate
      blood samples reflecting different sample qualities or disease conditions. This
      cell-based litmus gene assay identified six genes (CCL20, CEMIP, IL1B, IL8, PRG2,
      PTGS2) as potential biomarkers of plasma quality control and the SPC25 gene as a
      diagnostic biomarker of Alzheimer's disease (AD). In addition, the SPC25 gene
      expression level was significantly increased in the cell-based assay using serum
      samples from patients with mild cognitive impairment (MCI). In conclusion, we
      demonstrated the effectiveness and potential of a litmus gene assay to detect the
      orchestrated effects of circulating systemic factors, leading to the successful
      diagnosis of AD and MCI. This method is broadly applicable to the diagnosis of
      disease subtypes or patho-physiological stages of complex diseases and tumors.

PMID- 29203811
TI  - Characteristics of soil C:N ratio and delta13C in wheat-maize cropping system of
      the North China Plain and influences of the Yellow River.
AB  - To better understand the characteristics of soil organic matter (SOM) in the
      North China Plain, we evaluate the large scale variations of soil organic carbon
      (SOC), total nitrogen (TN), carbon to nitrogen (C:N) ratio and stable carbon
      isotopic compositions (delta13C) in SOC over 0-100 cm. To assess the influence of
      the Yellow River, 31 sites are selected from the wheat-maize double cropping
      system, and grouped into two: 10 sites near and 21 sites far from the river. Our
      data show that mean soil C:N ratio is low (7.6-9.9) across the region, and not
      affected by the Yellow River. However, SOC and TN are significantly (P < 0.05)
      lower in subsoil near the Yellow River (2.0 and 0.2-0.3 g kg-1 for SOC and TN)
      than far away (3.1 and 0.4 g kg-1); delta13C is significantly more negative below
      60 cm near the river (-23.3 to -22.60/00) than far away (-21.8 to -21.40/00). We
      estimate that the contributions of wheat and maize to SOC are 61.3-68.1% and 31.9
      38.8%, respectively. Our analyses indicate that the overall low levels of SOC in
      the North China Plain may be associated with the low soil C:N ratio and less clay
      content. The hydrological processes may also partly be responsible, particularly
      for those near the Yellow River.

PMID- 29203812
TI  - A highly printable and biocompatible hydrogel composite for direct printing of
      soft and perfusable vasculature-like structures.
AB  - Vascularization is one major obstacle in bioprinting and tissue engineering. In
      order to create thick tissues or organs that can function like original body
      parts, the presence of a perfusable vascular system is essential. However, it is
      challenging to bioprint a hydrogel-based three-dimensional vasculature-like
      structure in a single step. In this paper, we report a new hydrogel-based
      composite that offers impressive printability, shape integrity, and
      biocompatibility for 3D bioprinting of a perfusable complex vasculature-like
      structure. The hydrogel composite can be used on a non-liquid platform and is
      printable at human body temperature. Moreover, the hydrogel composite supports
      both cell proliferation and cell differentiation. Our results represent a
      potentially new vascularization strategy for 3D bioprinting and tissue
      engineering.

PMID- 29203813
TI  - Comparison of single- and double-balloon catheters for labor induction: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: There is a paucity of head-to-head randomized trials that compare
      single- and double-balloon catheters, and the results of the available data in
      terms of time from catheter insertion to delivery and delivery mode are mixed.
      This meta-analysis of randomized controlled trials compares the efficacy of
      single- and double-balloon catheters in women undergoing labor induction. STUDY
      DESIGN: Searches were made in MEDLINE, EMBASE, PubMed, ClinicalTrials.gov, and
      the Cochrane Library from inception through June 2016. Peer-reviewed randomized
      and quasi-randomized trials that compared single- and double-balloon catheters
      head-to-head for cervical ripening or labor induction were identified. Eligible
      study populations consisted of women with singleton pregnancies that had any
      indication for labor induction and were randomly assigned to undergo induction
      with a single- or a double-balloon catheter. The primary outcome was time from
      catheter insertion to delivery and delivery mode. The secondary outcomes were
      intrapartum fever or chorioamnionitis, woman's satisfaction, and neonatal Apgar
      score. RESULTS: Of the 520 records identified, five randomized trials (996 women;
      491 with single-balloon and 505 with double-balloon catheters) were considered
      eligible and included in the meta-analysis. Time from catheter insertion to
      delivery did not differ between the two types of catheter (p = 0.527; WMD -0.87;
      95% CI: -3.55, 1.82). The incidence of cesarean delivery also did not differ (p =
      0.844; RR 0.97; 95% CI: 0.69, 1.35). Delivery within 24 h, delivery mode,
      incidences of intrapartum fever or chorioamnionitis, and neonatal Apgar score <7
      at 5 min did not differ between the two types of catheter as well. Women who were
      induced with the single-balloon catheter were more satisfied (p = 0.029; WMD
      0.56; 95% CI: 0.06, 1.06). CONCLUSION: Time from catheter insertion to delivery
      and delivery mode were comparable between the two types of catheter.

PMID- 29203814
TI  - A label-free fiber optic SPR biosensor for specific detection of C-reactive
      protein.
AB  - A highly sensitive and label-free fiber optic surface plasmon resonance (SPR)
      biosensor for specific detection of C-reactive protein (CRP) is proposed and
      demonstrated. We take dopamine as a cross-linking agent to immobilize the anti
      CRP monoclonal antibody, which is an efficient and simple method for specific
      modification of the fiber optic SPR sensor. The modified sensor can successfully
      detect CRP specifically. We realize the fabrication of a disposable fiber optic
      SPR sensor for the CRP specific detection. Through optimizing the immobilization
      time of anti-CRP monoclonal antibody and the reaction time of antigen and
      antibody experimentally, the sensor shows a satisfactory linear response (R2 =
      0.97) to CRP concentration within the range from 0.01 to 20 MUg/ml. Moreover, the
      highest CRP sensitivity is obtained at 1.17 nm per lg (MUg/ml). With the
      advantages of simple structure and easy fabrication, our sensor is convenient to
      be batch produced and controlled with good consistency, which is especially
      suitable for the fabrication of disposable biosensor. It makes sense that our
      detection can effectively avoid the cross pollution caused by repeated use of the
      sensor.

PMID- 29203815
TI  - Role of ventral medullary catecholaminergic neurons for respiratory modulation of
      sympathetic outflow in rats.
AB  - Sympathetic activity displays rhythmic oscillations generated by brainstem
      inspiratory and expiratory neurons. Amplification of these rhythmic respiratory
      related oscillations is observed in rats under enhanced central respiratory drive
      or during development of neurogenic hypertension. Herein, we evaluated the
      involvement of ventral medullary sympatho-excitatory catecholaminergic C1
      neurons, using inhibitory Drosophila allatostatin receptors, for the enhanced
      expiratory-related oscillations in sympathetic activity in rats submitted to
      chronic intermittent hypoxia (CIH) and following activation of both peripheral
      (hypoxia) and central chemoreceptors (hypercapnia). Pharmacogenetic inhibition of
      C1 neurons bilaterally resulted in reductions of their firing frequency and
      amplitude of inspiratory-related sympathetic activity in rats in normocapnia,
      hypercapnia or after CIH. In contrast, hypercapnia or hypoxia-induced enhanced
      expiratory-related sympathetic oscillations were unaffected by C1 neuronal
      inhibition. Inhibition of C1 neurons also resulted in a significant fall in
      arterial pressure and heart rate that was similar in magnitude between
      normotensive and CIH hypertensive rats, but basal arterial pressure in CIH rats
      remained higher compared to controls. C1 neurons play a key role in regulating
      inspiratory modulation of sympathetic activity and arterial pressure in both
      normotensive and CIH hypertensive rats, but they are not involved in the enhanced
      late-expiratory-related sympathetic activity triggered by activation of
      peripheral or central chemoreceptors.

PMID- 29203816
TI  - Re-entrant spin glass transitions: new insights from acoustic absorption by
      domain walls.
AB  - Re-entrant spin glass (RSG) transitions in Ni-Mn and Au-Fe have been reassessed
      by acoustic measurements of the magneto-mechanical damping by domain walls.
      Stress-induced non-thermally activated domain wall dynamics is progressively
      replaced by an intense thermally activated relaxational response when the
      temperature approaches the RSG freezing point. A "frozen" state with negligible
      motion of domain walls on atomic and mesoscopic scales occurs in the RSG. We
      propose that RSG freezing has its origin in intrinsic properties of domain walls.

PMID- 29203817
TI  - High expression of beta-catenin contributes to the crizotinib resistant phenotype
      in the stem-like cell population in neuroblastoma.
AB  - ALK has been identified as a novel therapeutic target in neuroblastoma (NB), but
      resistance to ALK inhibitors (such as crizotinib) is well recognized. We recently
      published that the crizotinib sensitivity in NB cells strongly correlates with
      the crizotinib-ALK binding, and beta-catenin effectively hinders this interaction
      and confers crizotinib resistance. Here, we asked if these observations hold true
      for the stem-like cells in NB cells, which were purified based on their
      responsiveness to a Sox2 reporter. Compared to bulk, reporter unresponsive (RU)
      cells, reporter responsive (RR) cells had significantly higher neurosphere
      formation ability, expression of CD133/nestin and chemo-resistance. Using the
      cellular thermal shift assay, we found that RR cells exhibited significantly
      weaker crizotinib-ALK binding and higher crizotinib resistance than RU cells. The
      suboptimal crizotinib-ALK binding in RR cells can be attributed to their high
      beta-catenin expression, since siRNA knockdown of beta-catenin restored the
      crizotinib-ALK binding and lowered the crizotinib resistance to the level of RU
      cells. Enforced expression of beta-catenin in RU cells resulted in the opposite
      effects. To conclude, high expression of beta-catenin in the stem-like NB cells
      contributes to their crizotinib resistance. Combining beta-catenin inhibitors and
      ALK inhibitors may be useful in treating NB patients.

PMID- 29203818
TI  - Associations between general and central obesity and hypertension among children:
      The Childhood Obesity Study in China Mega-Cities.
AB  - In this study, we examined the associations of general and central obesity and
      hypertension among Chinese children. Data was collected from 1626 children aged 7
      16 years and their parents in four mega-cities across China. Mixed effect models
      examined associations of general and central obesity with hypertension, and
      between body mass index (BMI), waist circumference (WC), waist-to-height ratio
      (WHtR), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The
      prevalence of general obesity, central obesity, and hypertension among the
      children was 11.1%, 19.7%, and 9.0%, respectively. More boys had general and
      central obesity than girls (15.2% vs. 6.9%; 27.4% vs. 11.7%, respectively; both P
      < 0.0001). Sex difference in hypertension rate was not statistically significant
      (9.3% in boys vs. 8.8% in girls, P = 0.7341). Both SBP and DBP were positively
      associated with BMI, WC, and WHtR, regardless of sex and region. General obesity
      (OR = 5.94, 95% confidence interval [CI]: 3.69-9.55) and central obesity (OR =
      3.45, 95% CI: 2.27-5.23) were strongly associated with hypertension. The
      prevalence of general obesity, central obesity, and hypertension was high among
      Chinese children in the four mega-cities across China. Children's BMI, WC, and
      WHtR were positively associated with their SBP and DBP. Obese children were 3-6
      times more likely to have hypertension.

PMID- 29203819
TI  - Author Correction: Mining of efficient microbial UDP-glycosyltransferases by
      motif evolution cross plant kingdom for application in biosynthesis of
      salidroside.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29203820
TI  - Hydrogen and the Light-Induced Bias Instability Mechanism in Amorphous Oxide
      Semiconductors.
AB  - Hydrogen is known to be present as an impurity in amorphous oxide semiconductors
      at the 0.1% level. Using amorphous ZnO as a simplified model system, we show that
      the hydrogens pair up at oxygen vacancies in the amorphous network, where they
      form metal-H-metal bridge bonds. These bonds are shown to create filled defect
      gap states lying just above the valence band edge and they are shown to give a
      consistent mechanism to explain the negative bias illumination stress instability
      found in oxide semiconductors like In-Ga-Zn-O (IGZO).

PMID- 29203821
TI  - Localized solutions of Lugiato-Lefever equations with focused pump.
AB  - Lugiato-Lefever (LL) equations in one and two dimensions (1D and 2D) accurately
      describe the dynamics of optical fields in pumped lossy cavities with the
      intrinsic Kerr nonlinearity. The external pump is usually assumed to be uniform,
      but it can be made tightly focused too-in particular, for building small pixels.
      We obtain solutions of the LL equations, with both the focusing and defocusing
      intrinsic nonlinearity, for 1D and 2D confined modes supported by the localized
      pump. In the 1D setting, we first develop a simple perturbation theory, based in
      the sech ansatz, in the case of weak pump and loss. Then, a family of exact
      analytical solutions for spatially confined modes is produced for the pump
      focused in the form of a delta-function, with a nonlinear loss (two-photon
      absorption) added to the LL model. Numerical findings demonstrate that these
      exact solutions are stable, both dynamically and structurally (the latter means
      that stable numerical solutions close to the exact ones are found when a specific
      condition, necessary for the existence of the analytical solution, does not
      hold). In 2D, vast families of stable confined modes are produced by means of a
      variational approximation and full numerical simulations.

PMID- 29203822
TI  - Fluorescence brightness and photostability of individual copper (I) oxide
      nanocubes.
AB  - Conventional organic fluorophores lose their ability to fluoresce after repeated
      exposure to excitation light due to photobleaching. Therefore, research into
      emerging bright and photostable nanomaterials has become of great interest for a
      range of applications such as bio-imaging and tracking. Among these emerging
      fluorophores, metal oxide-based nanomaterials have attracted significant
      attention as a potential multifunctional material with photocatalytic and
      angeogenisis abilities in addition to fluorescnce applications. However, most of
      these applications are highly dependent on size, morphology, and chemo-physical
      properties of individual particles. In this manuscript, we present a method to
      study the intrinsic optical characteristics of individual copper (I) oxide (Cu2O)
      nanocubes. When excited at 520 nm using only 11 uW excitation power (1.7 W/cm2),
      individual nanocubes were observed to emit light with peak wavelengths ~760 nm
      which is conveniently within the near-infrared 1 (NIR1) biological window where
      tissue autofluorescence is minimal. Bright and photostable fluorescence was
      observed with intensities up to 487 K counts/s under constant illumination for at
      least 2 minutes with a brightness approximately four times higher than the
      autofluorescence from a fixed cumulus-oocyte complex. With near-IR emission, high
      fluorescence brightness, and outstanding photostability, Cu2O nanocubes are
      attractive candidates for long-term fluorescent bioimaging applications.

PMID- 29203824
TI  - Genetic engineering in nonhuman primates for human disease modeling.
AB  - Nonhuman primate (NHP) experimental models have contributed greatly to human
      health research by assessing the safety and efficacy of newly developed drugs,
      due to their physiological and anatomical similarities to humans. To generate NHP
      disease models, drug-inducible methods, and surgical treatment methods have been
      employed. Recent developments in genetic and developmental engineering in NHPs
      offer new options for producing genetically modified disease models. Moreover, in
      recent years, genome-editing technology has emerged to further promote this trend
      and the generation of disease model NHPs has entered a new era. In this review,
      we summarize the generation of conventional disease model NHPs and discuss new
      solutions to the problem of mosaicism in genome-editing technology.

PMID- 29203823
TI  - Three-dimensional organotypic matrices from alternative collagen sources as pre
      clinical models for cell biology.
AB  - Organotypic co-cultures bridge the gap between standard two-dimensional culture
      and mouse models. Such assays increase the fidelity of pre-clinical studies, to
      better inform lead compound development and address the increasing attrition
      rates of lead compounds within the pharmaceutical industry, which are often a
      result of screening in less faithful two-dimensional models. Using large-scale
      acid-extraction techniques, we demonstrate a step-by-step process to isolate
      collagen I from commercially available animal byproducts. Using the well
      established rat tail tendon collagen as a benchmark, we apply our novel kangaroo
      tail tendon collagen as an alternative collagen source for our screening-ready
      three-dimensional organotypic co-culture platform. Both collagen sources showed
      equal applicability for invasive, proliferative or survival assessment of well
      established cancer models and clinically relevant patient-derived cancer cell
      lines. Additional readouts were also demonstrated when comparing these
      alternative collagen sources for stromal contributions to stiffness, organization
      and ultrastructure via atomic force microscopy, second harmonic generation
      imaging and scanning electron microscopy, among other vital biological readouts,
      where only minor differences were found between the preparations. Organotypic co
      cultures represent an easy, affordable and scalable model to investigate drug
      responses within a physiologically relevant 3D platform.

PMID- 29203825
TI  - Adjuvant imatinib for patients with high-risk gastrointestinal stromal tumors: a
      retrospective cohort study.
AB  - The duration of adjuvant imatinib for high-risk patients with gastrointestinal
      stromal tumors (GISTs) is still controversial. Therefore, we retrospectively
      analyzed the data of high-risk patients with GISTs to investigate the appropriate
      duration. All 185 patients were divided into 4 groups: <1 year (Group A), 1-2
      years (Group B), 2-3 years (Group C) and >3 years (Group D). The mean recurrence
      free survival (RFS) in Groups A, B, and C were 44.3, 62.1, and 86.8 months,
      respectively (P < 0.001); the mean overall survival (OS) in Groups A, B and C was
      75.2, 88.1, and 94.7 months, respectively (P = 0.009). The 5-year RFS in Groups
      A, B, C, and D was 15%, 26%, 83%, and 100%, respectively (P < 0.001); and the 5
      year OS was 64%, 88%, 88%, and 100%, respectively (P < 0.001). The greatest
      impact on unfavorable outcomes was the tumor mitotic rate (HR, 2.01, 95% CI, 1.38
      2.94; P < 0.001). Duration of adjuvant imatinib was the only favorable factor
      (HR, -0.95, 95% CI, 0.93-0.97; P < 0.001). For high-risk patients with high tumor
      size or mitotic rate, or non-gastric GISTs, we recommend that more than 3 years
      of adjuvant imatinib is feasible.

PMID- 29203826
TI  - Blink associated resetting eye movements (BARMs) are functionally complementary
      to microsaccades in correcting for fixation errors.
AB  - Blinks do not only protect the eye, but they do also correct for torsional eye
      position deviations by blink-associated resetting eye movements (BARMs). Although
      BARMs are functionally distinct from other eye movements in the torsional
      dimension, it has remained open if BARMs observed in the horizontal and vertical
      dimensions (fixational BARMs) are not simply microsaccades coinciding with
      blinks. We show here that fixational BARMs are functionally distinct and
      complementary to microsaccades in the following way: First, they compensate for
      large fixational error more efficiently than microsaccades, secondly, their
      probability to be executed in eccentric eye positions is higher, and thirdly,
      they reset the eyes into a position zone that is broader as compared to
      microsaccades. This suggests that BARMs help to keep the eyes in a working range
      wherein microsaccades guarantee high acuity vision. Moreover, we establish that
      fixational BARMs operate in a retina-centric frame.

PMID- 29203827
TI  - Identification of early ammonium nitrate-responsive genes in rice roots.
AB  - Ammonium has long been used as the predominant form of nitrogen source for paddy
      rice (Oryza sativa). Recently, increasing evidence suggests that nitrate also
      plays an important role for nitrogen acquisition in the rhizosphere of
      waterlogged paddy rice. Ammonium and nitrate have a synergistic effect on
      promoting rice growth. However, the molecular responses induced by simultaneous
      treatment with ammonium and nitrate have been less studied in rice. Here, we
      performed transcriptome analysis to identify genes that are rapidly regulated by
      ammonium nitrate (1.43 mM, 30 min) in rice roots. The combination of ammonium and
      nitrate preferentially induced the expression of nitrate-responsive genes. Gene
      ontology enrichment analysis revealed that the early ammonium nitrate-responsive
      genes were enriched in "regulation of transcription, DNA-dependent" and "protein
      amino acid phosphorylation" indicating that some of the genes identified in this
      study may play an important role in nitrogen sensing and signaling. Several
      defense/stress-responsive genes, including some encoding transcription factors
      and mitogen-activated protein kinase kinase kinases, were also rapidly induced by
      ammonium nitrate. These results suggest that nitrogen metabolism, signaling, and
      defense/stress responses are interconnected. Some of the genes identified here
      may be involved in the interaction of nitrogen signaling and defense/stress
      response pathways in plants.

PMID- 29203828
TI  - FOXP2 variation in great ape populations offers insight into the evolution of
      communication skills.
AB  - The gene coding for the forkhead box protein P2 (FOXP2) is associated with human
      language disorders. Evolutionary changes in this gene are hypothesized to have
      contributed to the emergence of speech and language in the human lineage.
      Although FOXP2 is highly conserved across most mammals, humans differ at two
      functional amino acid substitutions from chimpanzees, bonobos and gorillas, with
      an additional fixed substitution found in orangutans. However, FOXP2 has been
      characterized in only a small number of apes and no publication to date has
      examined the degree of natural variation in large samples of unrelated great
      apes. Here, we analyzed the genetic variation in the FOXP2 coding sequence in 63
      chimpanzees, 11 bonobos, 48 gorillas, 37 orangutans and 2 gibbons and observed
      undescribed variation in great apes. We identified two variable polyglutamine
      microsatellites in chimpanzees and orangutans and found three nonsynonymous
      single nucleotide polymorphisms, one in chimpanzees, one in gorillas and one in
      orangutans with derived allele frequencies of 0.01, 0.26 and 0.29, respectively.
      Structural and functional protein modeling indicate a biochemical effect of the
      substitution in orangutans, and because of its presence solely in the Sumatran
      orangutan species, the mutation may be associated with reported population
      differences in vocalizations.

PMID- 29203829
TI  - IL-4 driven transcription factor FoxQ1 is expressed by monocytes in atopic
      dermatitis and stimulates monocyte migration.
AB  - Monocytes are actively recruited at sites of chronic inflammation. However,
      molecular factors involved in this process are not fully elucidated. Here, we
      show that cytokine IL-4 which is implicated in the development of chronic
      inflammatory disease atopic dermatitis (AD) induces expression of transcription
      factor FoxQ1 in human monocytes and macrophages. FoxQ1 mRNA levels were elevated
      in monocytes of AD patients compared to healthy donors. Overexpression of FoxQ1
      in RAW 264.7 monocytic cells facilitated their migration towards MCP-1 and was
      associated with decreased expression of migration-regulating genes (claudin 11
      and plexin C1). Furthermore, FoxQ1 overexpression in RAW cells accelerated
      TNFalpha secretion after LPS challenge. Overall, our results indicate that FoxQ1
      stimulates monocyte motility, increases pro-inflammatory potential, and directs
      monocyte migration towards MCP-1 that is crucial for monocyte influx into
      inflammatory sites. This mechanism could contribute to the pathogenesis of
      chronic inflammatory disorders such as AD.

PMID- 29203830
TI  - Cascaded gain-switching in the mid-infrared region.
AB  - In this report, we demonstrate mid-infrared dual-waveband (i.e., ~3 MUm and ~2
      MUm) pulses from a cascaded gain-switched Ho3+-doped ZBLAN fiber laser by the use
      of hybrid pumping of 1150 nm CW and pulse LDs for the first time. Stable ~3 MUm
      gain-switched pulses with the maximum output power 262.14 mW and shortest pulse
      duration of 0.824 MUs were first gained at the repetition rate of 80 kHz and
      wavelength of 2928.5 nm. Then stable ~2 MUm gain-switched pulses at 2068 nm were
      achieved at a switchable repetition rate between 40 kHz and 80 kHz. The maximum
      output power and shortest pulse duration were 75.23 mW and 0.787 MUs,
      respectively (not simultaneously). Between them, there is a power-dependent MUs
      order time delay. This dual-waveband laser source has great potential in laser
      surgery, material processing.

PMID- 29203831
TI  - Germanium-doped Metallic Ohmic Contacts in Black Phosphorus Field-Effect
      Transistors with Ultra-low Contact Resistance.
AB  - In this work, we demonstrate for the first time an ultra-low contact resistance
      few-layered black phosphorus (BP) transistor with metallic PGex contacts formed
      by rapid thermal annealing (RTA). The on-state current of the transistor can be
      significantly improved and the ION/IOFF ratio increases by almost 2 order. The
      hole mobility is enhanced by 25 times to 227 cm2V-1s-1. The contact resistance
      extracted by the transfer length method is 0.365 kOmega?MUm, which is the lowest
      value in black phosphorus transistors without degradation of ION/IOFF ratio. In
      addition, the I-V curve of the transistor with PGex contact is linear compared to
      that with Ti contact at 80 K, indicating that a metallic ohmic contact is
      successfully formed. Finally, X-ray photoelectron spectroscopy is used to
      characterize the PGex compound. A signal of P-Ge bond is first observed, further
      verifying the doping of Ge into BP and the formation of the PGex alloy.

PMID- 29203832
TI  - Efficient and flexible implementation of Langevin simulation for gene burst
      production.
AB  - Gene expression involves bursts of production of both mRNA and protein, and the
      fluctuations in their number are increased due to such bursts. The Langevin
      equation is an efficient and versatile means to simulate such number fluctuation.
      However, how to include these mRNA and protein bursts in the Langevin equation is
      not intuitively clear. In this work, we estimated the variance in burst
      production from a general gene expression model and introduced such variation in
      the Langevin equation. Our approach offers different Langevin expressions for
      either or both transcriptional and translational bursts considered and saves
      computer time by including many production events at once in a short burst time.
      The errors can be controlled to be rather precise (<2%) for the mean and <10% for
      the standard deviation of the steady-state distribution. Our scheme allows for
      high-quality stochastic simulations with the Langevin equation for gene
      expression, which is useful in analysis of biological networks.

PMID- 29203833
TI  - Bayesian analysis of genome-wide inflammatory bowel disease data sets reveals new
      risk loci.
AB  - Genome-wide association studies (GWAS) have identified and validated 200 risk
      loci for inflammatory bowel disease (IBD) to date, including risk loci for both
      Crohn's disease and ulcerative colitis. Previously studies mainly used single SNP
      testing methods and only reported the most significant association within each
      locus. Advanced methods are needed to detect additional joint effects of multiple
      SNPs and fine map causal variants in presence of strong linkage disequilibrium.
      In this study, we applied a powerful Bayesian method to analyze an existing
      Immunochip data sets for IBD from the international inflammatory bowel disease
      genetics consortium. The method jointly tested single and set-based SNPs in a
      unified framework and filtered indirect associations due to linkage
      disequilibrium, thereby fine-mapping the most likely IBD variants. Using an
      independent collection of individuals from 11 IBD GWAS as validation, our
      approach discovered and validated 9 completely new IBD loci and 5 independent
      signals (excluding the major histocompatibility complex) near known IBD loci
      reaching genome-wide significance. Several of the replicated new loci implicated
      functionally more interpretable genes than previous reports. The epigenetic marks
      at our detected IBD signals demonstrated significant activation signatures in
      blood cell types and correspondingly substantial repression in stem cells,
      suggesting regulatory links between genetic variants and IBD. Our analysis of the
      currently largest IBD datasets therefore added new insights that will be integral
      to the ongoing efforts in IBD genetics.

PMID- 29203834
TI  - Molecular and cellular issues of KMT2A variants involved in Wiedemann-Steiner
      syndrome.
AB  - Variants in KMT2A, encoding the histone methyltransferase KMT2A, are a growing
      cause of intellectual disability (ID). Up to now, the majority of KMT2A variants
      are non-sense and frameshift variants causing a typical form of Wiedemann-Steiner
      syndrome. We studied KMT2A gene in a cohort of 200 patients with unexplained
      syndromic and non-syndromic ID and identified four novel variants, one splice and
      three missense variants, possibly deleterious. We used primary cells from the
      patients and molecular approaches to determine the deleterious effects of those
      variants on KMT2A expression and function. For the putative splice variant
      c.11322-1G>A, we showed that it led to only one nucleotide deletion and loss of
      the C-terminal part of the protein. For two studied KMT2A missense variants,
      c.3460C>T (p.(Arg1154Trp)) and c.8558T>G (p.(Met2853Arg)), located at the
      cysteine-rich CXXC domain and the transactivation domain of the protein,
      respectively, we found altered KMT2A target genes expression in patient's
      fibroblasts compared to controls. Furthermore, we found a disturbed subcellular
      distribution of KMT2A for the c.3460C>T mutant. Taken together, our results
      demonstrated the deleterious impact of the splice variant and of the missense
      variants located at two different functional domains and suggested reduction of
      KMT2A function as the disease-causing mechanism.

PMID- 29203836
TI  - Lung cancer: Osimertinib strengthens the frontline.

PMID- 29203835
TI  - Purification and functional comparison of nine human Aquaporins produced in
      Saccharomyces cerevisiae for the purpose of biophysical characterization.
AB  - The sparse number of high-resolution human membrane protein structures severely
      restricts our comprehension of molecular physiology and ability to exploit
      rational drug design. In the search for a standardized, cheap and easily handled
      human membrane protein production platform, we thoroughly investigated the
      capacity of S. cerevisiae to deliver high yields of prime quality human AQPs,
      focusing on poorly characterized members including some previously shown to be
      difficult to isolate. Exploiting GFP labeled forms we comprehensively optimized
      production and purification procedures resulting in satisfactory yields of all
      nine AQP targets. We applied the obtained knowledge to successfully upscale
      purification of histidine tagged human AQP10 produced in large bioreactors.
      Glycosylation analysis revealed that AQP7 and 12 were O-glycosylated, AQP10 was N
      glycosylated while the other AQPs were not glycosylated. We furthermore performed
      functional characterization and found that AQP 2, 6 and 8 allowed flux of water
      whereas AQP3, 7, 9, 10, 11 and 12 also facilitated a glycerol flux. In
      conclusion, our S. cerevisiae platform emerges as a powerful tool for isolation
      of functional, difficult-to-express human membrane proteins suitable for
      biophysical characterization.

PMID- 29203837
TI  - Urothelial cancer in 2017: Changes in expectations for metastatic urothelial
      carcinoma.

PMID- 29203838
TI  - Immunotherapy: New or second CARs for ALL.

PMID- 29203839
TI  - Generation of photonic entanglement in green fluorescent proteins.
AB  - Recent development of spectroscopic techniques based on quantum states of light
      can precipitate many breakthroughs in observing and controlling light-matter
      interactions in biological materials on a fundamental quantum level. For this
      reason, the generation of entangled light in biologically produced fluorescent
      proteins would be promising because of their biocompatibility. Here we
      demonstrate the generation of polarization-entangled two-photon state through
      spontaneous four-wave mixing in enhanced green fluorescent proteins. The
      reconstructed density matrix indicates that the entangled state is subject to
      decoherence originating from two-photon absorption. However, the prepared state
      is less sensitive to environmental decoherence because of the protective beta
      barrel structure that encapsulates the fluorophore in the protein. We further
      explore the quantumness, including classical and quantum correlations, of the
      state in the decoherence environment. Our method for photonic entanglement
      generation may have potential for developing quantum spectroscopic techniques and
      quantum-enhanced measurements in biological materials.

PMID- 29203840
TI  - Enhancement of eruption explosivity by heterogeneous bubble nucleation triggered
      by magma mingling.
AB  - We present new evidence that shows magma mingling can be a key process during
      highly explosive eruptions. Using fractal analysis of the size distribution of
      trachybasaltic fragments found on the inner walls of bubbles in trachytic
      pumices, we show that the more mafic component underwent fracturing during
      quenching against the trachyte. We propose a new mechanism for how this magmatic
      interaction at depth triggered rapid heterogeneous bubble nucleation and growth
      and could have enhanced eruption explosivity. We argue that the data support a
      further, and hitherto unreported contribution of magma mingling to highly
      explosive eruptions. This has implications for hazard assessment for those
      volcanoes in which evidence of magma mingling exists.

PMID- 29203841
TI  - Asymmetric adiabatic couplers for fully-integrated broadband quantum-polarization
      state preparation.
AB  - Spontaneous parametric down-conversion (SPDC) is a widely used method to generate
      entangled photons, enabling a range of applications from secure communication to
      tests of quantum physics. Integrating SPDC on a chip provides interferometric
      stability, allows to reduce a physical footprint, and opens a pathway to true
      scalability. However, dealing with different photon polarizations and wavelengths
      on a chip presents a number of challenging problems. In this work, we demonstrate
      an on-chip polarization beam-splitter based on z-cut titanium-diffused lithium
      niobate asymmetric adiabatic couplers (AAC) designed for integration with a type
      II SPDC source. Our experimental measurements reveal unique polarization beam
      splitting regime with the ability to tune the splitting ratios based on
      wavelength. In particular, we measured a splitting ratio of 17 dB over broadband
      regions (>60 nm) for both H- and V-polarized lights and a specific 50%/50%
      splitting ratio for a cross-polarized photon pair from the AAC. The results show
      that such a system can be used for preparing different quantum polarization-path
      states that are controllable by changing the phase-matching conditions in the
      SPDC over a broad band. Furthermore, we propose a fully integrated electro
      optically tunable type-II SPDC polarization-path-entangled state preparation
      circuit on a single lithium niobate photonic chip.

PMID- 29203842
TI  - Tolerability and adequate therapeutic dosage of oral clomipramine for the
      treatment of premature ejaculation: A randomized, double-blind, placebo
      controlled, fixed-dose, parallel-grouped clinical study.
AB  - To evaluate the adequate therapeutic dosage of clomipramine 15 mg/day and
      clomipramine 30 mg/day in male patients with premature ejaculation (PE), this
      study enrolled men aged 20-65 years who met diagnostic criteria for PE including
      Intravaginal Ejaculation Latency Time (IELT) less than 2 min for at least 75% of
      their sexual intercourses. Subjects received placebo, clomipramine 15 mg, or
      clomipramine 30 mg prn (2~6 h before intercourse) for 4 weeks. Efficacy was
      assessed using fold change, percentile change, and mean change of IELT, as well
      as Drug Coitus Interval Time (DCIT). A total of 101 patients were randomized into
      the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group.
      Analyses of fold changes of IELT in each group revealed that the IELT of both the
      clomipramine 15 mg group and clomipramine 30 mg group was significantly increased
      4 weeks after administration than the placebo group. Adverse events were reported
      by 11.76, 32.35, and 57.57% of patients in the placebo group, clomipramine 15 mg
      group, and clomipramine 30 mg group, respectively. Most common adverse events in
      the clomipramine treatment groups were gastrointestinal disorders and psychiatric
      disorders of mild to moderate severity. On-demand regimen of clomipramine 15 mg
      resulted in a significant improvement in IELT and was superior to a regimen of
      clomipramine 30 mg in terms of risk-to-benefit ratio.

PMID- 29203843
TI  - Bisexuality among a cohort of university students: prevalence and psychological
      distress.
AB  - Sociocultural prejudices and pressures may impair the mental health of bisexual
      people. We aim to evaluate psychological status according to sexual orientation
      in a sample of Italian university students, with specific attention to
      bisexuality and its frequency. Among a recruited sample of 551 university
      students, we found the following percentages for sexual orientation:
      heterosexuals 96.9% (n = 534), homosexuals 1.1% (n = 6), bisexuals 2% (n = 11).
      The cross-sectional analysis for psychological symptoms, with the Symptoms Check
      List-90 Revised (SCL-90-R), revealed that bisexual subjects have statistically
      significant higher scores on some symptomatic scales compared to heterosexuals.
      In particular, obsession-compulsion, paranoid ideation, hostility were
      significantly higher in bisexuals. Therefore, if heterosexual or homosexual
      orientation are not specified by particular psychological symptoms, bisexuality
      is characterized by a strong link with some facets of psychological distress,
      which are likely caused by a peculiar double stigma. In conclusion, through a
      specific psychometric tool, we found an association between bisexuality and
      various forms of psychological suffering. This evidence should further encourage
      clinicians to accurately assess the psychological health in young bisexual
      people.

PMID- 29203844
TI  - Complications, functional and quality of life outcomes following primary and
      secondary implantation of penile prosthesis at a tertiary referral center.
AB  - The implantation of a penile prosthesis (PP) may be recommended in patients with
      severe erectile dysfunction (ED) who do not respond to conservative treatments.
      The aim of this study was to evaluate complications, as well as functional and
      quality of life outcomes following primary and secondary implantation of PP at a
      tertiary referral center. In this retrospective study, a total of 51 patients (41
      patients with primary (PPP) and 10 with secondary PP (SPP)) were included.
      Patients and operative characteristics were recorded and complications were
      analyzed using the Clavien-Dindo classification. To evaluate satisfaction of
      patients and their partners, as well as PP long-term function, follow-up data
      were collected by using questionnaires (Erectile Dysfunction Inventory of
      Treatment Satisfaction (EDITS) and QLQC30). Fifty-one patients with a median age
      of 61 years (IQR 52-68) received PP implantation (44 AMS 700, 7 Coloplast Titan).
      Main causes of ED were after radical prostatectomy (27.5%), diabetes (21,6%), and
      other unknown reasons (43.1%). Median time of intervention was 94.5 min (IQR 80.8
      110.3) with no significant difference between PPP and SPP. Only one patient
      undergoing PPP surgery had grade 3 complication. Follow-up data from a total of
      43 patients (84.3%) with a median follow-up of 26 months (IQR 17-41 mo) was
      recorded. At the time of follow-up, 88.4% of the PPs were still functional (PPP n
      = 34 (94.4%), SPP n = 4 (57.1%), p = 0.024). Overall estimated mean PP survival
      was 63.0 mo ((95% CI) 56.2-70.8 mo) with no significant difference between PPP
      and SPP. Overall satisfaction (EDITS und QLQC30) was high in both groups with no
      significant difference. PP implantation shows to be a safe treatment option in
      the management of severe ED.

PMID- 29203845
TI  - Enteral Tube Feeding in Paediatric Mitochondrial Diseases.
AB  - We investigated the effects of enteral tube feeding in Korean children with
      mitochondrial diseases. We performed a retrospective chart review of 68
      paediatric patients with mitochondrial diseases on enteral tube feeding at a
      tertiary referral centre. The outcome of enteral nutrition was evaluated by
      decrease in gastrointestinal (GI) symptoms, weight gain, and increase in
      developmental quotient (DQ) among patients with data available. Among 68
      patients, 56 (82%) were on gastrostomy and 12 (18%) were on prolonged nasogastric
      (NG) tube feeding. Decrease of GI symptoms was present in 37 of 48 patients
      (77%). Weight gain was present in 18 of 64 patients (28%) and was more prominent
      in the gastrostomy group (n = 17/54, 32%). Increase in DQ was similar between the
      NG tube and gastrostomy groups (total n = 10/48, 21%). Complications occurred in
      42% (n = 5/12) of the NG tube group and 64% (n = 36/56) of the gastrostomy group.
      They varied in range, from mild to severe. Most complications were minor; there
      were 5 cases (9%) requiring gastrostomy removal or additional procedure and 2
      cases (4%) of gastrostomy-related morbidity. Our results show that in paediatric
      patients with mitochondrial diseases, enteral tube feeding could help enhance
      quality of life by relieving GI symptoms, ameliorate growth failure and enhance
      development.

PMID- 29203846
TI  - Sero-catalytic and Antibody Acquisition Models to Estimate Differing Malaria
      Transmission Intensities in Western Kenya.
AB  - We sought to identify a subset of Plasmodium falciparum antibody targets that
      would inform monitoring efforts needed to eliminate malaria in high transmission
      settings. IgG antibodies to 28 recombinant Pf antigens were measured in residents
      of two communities in western Kenya examined in 2003 and 2013, when the
      respective prevalence of asymptomatic parasitemia among children was 81 and 15
      percent by microscopy. Annual seroconversion rates based on a sero-catalytic
      model that dichotomised antibody values to negative versus positive showed that
      rates were higher in 2003 than 2013 for 1 pre-erythrocytic and 7 blood-stage
      antigens. Antibody acquisition models that considered antibody levels as
      continuous variables showed that age-related antibody levels to Circumsporozoite
      Protein and 10 merozoite proteins increased at different rates with age in 2003
      versus 2013. Both models found that antibodies to 5 proteins of the Merozoite
      Surface Protein 1 complex were differentially acquired between the cohorts, and
      that changes in antibody levels to Apical Membrane Antigen 1 suggested a decrease
      in transmission that occurred ~10 years before 2013. Further studies evaluating
      antibodies to this subset of Pf antigens as biomarkers of malaria exposure and
      naturally acquired immunity are warranted in endemic settings where transmission
      has been reduced but persists.

PMID- 29203848
TI  - BDNF release and signaling are required for the antidepressant actions of GLYX
      13.
AB  - Conventional antidepressant medications, which act on monoaminergic systems,
      display significant limitations, including a time lag of weeks to months and low
      rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that
      acts as an N-methyl-D-aspartate (NMDA) modulator with glycine-like partial
      agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces
      rapid antidepressant actions in depressed patients and in preclinical rodent
      models. However, the mechanisms underlying the antidepressant actions of GLYX-13
      have not been characterized. Here we use a combination of neutralizing antibody
      (nAb), mutant mouse and pharmacological approaches to test the role of brain
      derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TrkB) signaling in
      the actions of GLYX-13. The results demonstrate that the antidepressant effects
      of GLYX-13 are blocked by intra-medial prefrontal cortex (intra-mPFC) infusion of
      an anti-BDNF nAb or in mice with a knock-in of the BDNF Val66Met allele, which
      blocks the processing and activity-dependent release of BDNF. We also demonstrate
      that pharmacological inhibitors of BDNF-TrkB signaling or of L-type voltage
      dependent Ca2+ channels (VDCCs) block the antidepressant behavioral actions of
      GLYX-13. Finally, we examined the role of the Rho GTPase proteins by injecting a
      selective inhibitor into the mPFC and found that activation of Rac1 but not RhoA
      is involved in the antidepressant effects of GLYX-13. Together, these findings
      indicate that enhanced release of BDNF through exocytosis caused by activation of
      VDCCs and subsequent TrkB-Rac1 signaling is required for the rapid and sustained
      antidepressant effects of GLYX-13.

PMID- 29203847
TI  - Reconceptualization of translocator protein as a biomarker of neuroinflammation
      in psychiatry.
AB  - A great deal of interest in psychiatric research is currently centered upon the
      pathogenic role of inflammatory processes. Positron emission tomography (PET)
      using radiolabeled ligands selective for the 18 kDa translocator protein (TSPO)
      has become the most widely used technique to assess putative neuroimmune
      abnormalities in vivo. Originally used to detect discrete neurotoxic damages,
      TSPO has generally turned into a biomarker of 'neuroinflammation' or 'microglial
      activation'. Psychiatric research has mostly accepted these denotations of TSPO,
      even if they may be inadequate and misleading under many pathological conditions.
      A reliable and neurobiologically meaningful diagnosis of 'neuroinflammation' or
      'microglial activation' is unlikely to be achieved by the sole use of TSPO PET
      imaging. It is also very likely that the pathological meanings of altered TSPO
      binding or expression are disease-specific, and therefore, not easily
      generalizable across different neuropathologies or inflammatory conditions. This
      difficulty is intricately linked to the varying (and still ill-defined)
      physiological functions and cellular expression patterns of TSPO in health and
      disease. While altered TSPO binding or expression may indeed mirror ongoing
      neuroinflammatory processes in some cases, it may reflect other
      pathophysiological processes such as abnormalities in cell metabolism, energy
      production and oxidative stress in others. Hence, the increasing popularity of
      TSPO PET imaging has paradoxically introduced substantial uncertainty regarding
      the nature and meaning of neuroinflammatory processes and microglial activation
      in psychiatry, and likely in other neuropathological conditions as well. The
      ambiguity of conceiving TSPO simply as a biomarker of 'neuroinflammation' or
      'microglial activation' calls for alternative interpretations and complimentary
      approaches. Without the latter, the ongoing scientific efforts and excitement
      surrounding the role of the neuroimmune system in psychiatry may not turn into
      therapeutic hope for affected individuals.

PMID- 29203849
TI  - An integrated brain-behavior model for working memory.
AB  - Working memory (WM) is a central construct in cognitive neuroscience because it
      comprises mechanisms of active information maintenance and cognitive control that
      underpin most complex cognitive behavior. Individual variation in WM has been
      associated with multiple behavioral and health features including demographic
      characteristics, cognitive and physical traits and lifestyle choices. In this
      context, we used sparse canonical correlation analyses (sCCAs) to determine the
      covariation between brain imaging metrics of WM-network activation and
      connectivity and nonimaging measures relating to sensorimotor processing,
      affective and nonaffective cognition, mental health and personality, physical
      health and lifestyle choices derived from 823 healthy participants derived from
      the Human Connectome Project. We conducted sCCAs at two levels: a global level,
      testing the overall association between the entire imaging and behavioral-health
      data sets; and a modular level, testing associations between subsets of the two
      data sets. The behavioral-health and neuroimaging data sets showed significant
      interdependency. Variables with positive correlation to the neuroimaging variate
      represented higher physical endurance and fluid intelligence as well as better
      function in multiple higher-order cognitive domains. Negatively correlated
      variables represented indicators of suboptimal cardiovascular and metabolic
      control and lifestyle choices such as alcohol and nicotine use. These results
      underscore the importance of accounting for behavioral-health factors in
      neuroimaging studies of WM and provide a neuroscience-informed framework for
      personalized and public health interventions to promote and maintain the
      integrity of the WM network.

PMID- 29203850
TI  - Polygenic prediction of obsessive compulsive symptoms.

PMID- 29203851
TI  - Dynamic landscape of the local translation at activated synapses.
AB  - The mammalian target of rapamycin (mTOR) signaling pathway is the central
      regulator of cap-dependent translation at the synapse. Disturbances in mTOR
      pathway have been associated with several neurological diseases, such as autism
      and epilepsy. RNA-binding protein FMRP, a negative regulator of translation
      initiation, is one of the key components of the local translation system.
      Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and
      dephosphorylation by PP2A phosphatase, respectively. S6 kinase and PP2A
      phosphatase are activated in response to mGluR receptor stimulation through
      different signaling pathways and at different rates. The dynamic aspects of this
      system are poorly understood. We developed a mathematical model of FMRP-dependent
      regulation of postsynaptic density (PSD) protein synthesis in response to mGluR
      receptor stimulation and conducted in silico experiments to study the regulatory
      circuit functioning. The modeling results revealed the possibility of generating
      oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of
      postsynaptic protein synthesis as well as the presence of multiple attractors in
      a wide range of parameters of the local translation system. The results suggest
      that autistic disorders associated with mTOR pathway hyperactivation may be due
      to impaired proteome stability associated with the formation of complex dynamic
      regimes of PSD protein synthesis in response to stimulation of mGluR receptors on
      the postsynaptic membrane of excitatory synapses on pyramidal hippocampal cells.

PMID- 29203852
TI  - The dynamics of stress: a longitudinal MRI study of rat brain structure and
      connectome.
AB  - Stress is a well-established trigger for a number of neuropsychiatric disorders,
      as it alters both structure and function of several brain regions and its
      networks. Herein, we conduct a longitudinal neuroimaging study to assess how a
      chronic unpredictable stress protocol impacts the structure of the rat brain and
      its functional connectome in both high and low responders to stress. Our results
      reveal the changes that stress triggers in the brain, with structural atrophy
      affecting key regions such as the prelimbic, cingulate, insular and
      retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices,
      the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed
      nucleus of the stria terminalis, the thalamus and several brain stem nuclei.
      These structural changes are associated with increasing functional connectivity
      within a network composed by these regions. Moreover, using a clustering based on
      endocrine and behavioural outcomes, animals were classified as high and low
      responders to stress. We reveal that susceptible animals (high responders)
      develop local atrophy of the ventral tegmental area and an increase in functional
      connectivity between this area and the thalamus, further spreading to other areas
      that link the cognitive system with the fight-or-flight system. Through a
      longitudinal approach we were able to establish two distinct patterns, with
      functional changes occurring during the exposure to stress, but with an
      inflection point after the first week of stress when more prominent changes were
      seen. Finally, our study revealed differences in functional connectivity in a
      brainstem-limbic network that distinguishes resistant and susceptible responders
      before any exposure to stress, providing the first potential imaging-based
      predictive biomarkers of an individual's resilience/vulnerability to stressful
      conditions.

PMID- 29203853
TI  - Quantitative Analysis of Inflammation in Orbital Fat of Thyroid-associated
      Ophthalmopathy Using MRI Signal Intensity.
AB  - We quantitatively analyzed inflammation in orbital fat from cases of thyroid
      associated ophthalmopathy (TAO) using short-tau inversion recovery (STIR)
      sequences from magnetic resonance imaging. The signal intensity ratios (SIRs) of
      orbital fat as well as the superior rectus (SR), inferior rectus (IR), lateral
      rectus (LR), medial rectus (MR), and superior oblique (SO) muscles on STIR images
      were measured in 70 eyes from 70 treatment-naive TAO patients (active TAO group,
      19 patients; inactive TAO group, 51 patients) and 20 eyes from 20 controls. The
      mean SIR in the active TAO group was significantly higher than that in the
      inactive TAO group and controls (P < 0.001). The SIR of orbital fat in all TAO
      patients was significantly (P < 0.001) positively correlated with that of the
      extraocular muscles: SR (r = 0.64), IR (r = 0.55), LR (r = 0.58), MR (r = 0.71),
      and SO (r = 0.65). The SIR of orbital fat had a significant positive correlation
      with the CAS (r = 0.53, P < 0.001). The measurements of SIRs in orbital fat may
      be useful in evaluating the activity in tissues of TAO patients.

PMID- 29203855
TI  - Effect of consolidation chemotherapy following definitive chemoradiotherapy in
      patients with esophageal squamous cell cancer.
AB  - Definitive chemoradiotherapy (dCRT) is a treatment option for patients with
      localized esophageal squamous cell carcinoma (ESCC). We investigated
      consolidation chemotherapy (CCT) in patients with ESCC who attained clinical
      complete response after dCRT. Between January 2009 and December 2012, medical
      records of ESCC patients treated with dCRT were retrospectively reviewed, and
      those who attained CCR were identified. Progression-free survival and overall
      survival rates were estimated by the Kaplan-Meier method. The Cox regression
      model was used to determine prognostic factors. Of the 522 patients treated with
      dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy
      (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not
      prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95%
      CI, 0.48-1.04); however, CCT improved the median overall survival (53.4 vs 27.0
      months, P = 0.04, HR = 0.67, 95% CI, 0.44-0.99) compared with dCRT alone. CCT
      remained a favorable prognostic factor for overall survival in a multivariate
      analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to
      show an additional overall survival benefit with CCT. In the present analysis,
      CCT did not improve progression-free survival but may have extended overall
      survival in ESCC patients who achieved complete clinical response after dCRT.

PMID- 29203854
TI  - Distributed neural representation of saliency controlled value and category
      during anticipation of rewards and punishments.
AB  - An extensive literature from cognitive neuroscience examines the neural
      representation of value, but interpretations of these existing results are often
      complicated by the potential confound of saliency. At the same time, recent
      attempts to dissociate neural signals of value and saliency have not addressed
      their relationship with category information. Using a multi-category valuation
      task that incorporates rewards and punishments of different nature, we identify
      distributed neural representation of value, saliency, and category during outcome
      anticipation. Moreover, we reveal category encoding in multi-voxel blood-oxygen
      level-dependent activity patterns of the vmPFC and the striatum that coexist with
      value signals. These results help clarify ambiguities regarding value and
      saliency encoding in the human brain and their category independence, lending
      strong support to the neural "common currency" hypothesis. Our results also point
      to potential novel mechanisms of integrating multiple aspects of decision-related
      information.

PMID- 29203856
TI  - Somatic CLL mutations occur at multiple distinct hematopoietic maturation stages:
      documentation and cautionary note regarding cell fraction purity.

PMID- 29203857
TI  - CO2 fixation in above-ground biomass of summer maize under different tillage and
      straw management treatments.
AB  - This study was conducted to quantify the potential for CO2 fixation in the above
      ground biomass of summer maize (Zea mays L.) under different tillage and residue
      retention treatments. The treatments were paired and included conventional
      tillage with straw removed (CT0), conventional tillage with straw retained (CTS),
      no-till with straw removed (NT0), no-till with straw retention (NTS), subsoiling
      with straw removed (SS0), and subsoiling with straw retained (SSS). The results
      indicated that NTS and SSS can enhance translocation of photosynthates to grains
      during the post-anthesis stage. SSS showed the highest total production (average
      of 7.8 Mg ha-1), carbon absorption by crop (Cd) (average of 9.2 Mg C ha-1), and
      total C absorption (Ct) (average of 40.4 Mg C ha-1); and NTS showed the highest
      contribution of post-anthesis dry matter translocation to grain yield (average of
      74%). Higher CO2 emission intensity and CO2 fixation efficiency (CFE) were
      observed for straw retention treatments. In comparison with CTS, the mean CFE (%)
      over four years increased by 26.3, 19.0, 16.5, and 9.4 for NT0, SS0, NTS, and
      SSS, respectively. Thus, SSS and NTS systems offer the best options for removing
      CO2 from the atmosphere while enhancing crop productivity of summer maize in the
      North China Plain.

PMID- 29203858
TI  - Complete 3-Qubit Grover search on a programmable quantum computer.
AB  - The Grover quantum search algorithm is a hallmark application of a quantum
      computer with a well-known speedup over classical searches of an unsorted
      database. Here, we report results for a complete three-qubit Grover search
      algorithm using the scalable quantum computing technology of trapped atomic ions,
      with better-than-classical performance. Two methods of state marking are used for
      the oracles: a phase-flip method employed by other experimental demonstrations,
      and a Boolean method requiring an ancilla qubit that is directly equivalent to
      the state marking scheme required to perform a classical search. We also report
      the deterministic implementation of a Toffoli-4 gate, which is used along with
      Toffoli-3 gates to construct the algorithms; these gates have process fidelities
      of 70.5% and 89.6%, respectively.

PMID- 29203859
TI  - Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote
      glioblastoma multiforme.
AB  - The interleukin-13 receptor alpha2 (IL-13Ralpha2) is a cancer-associated receptor
      overexpressed in human glioblastoma multiforme (GBM). This receptor is
      undetectable in normal brain which makes it a highly suitable target for
      diagnostic and therapeutic purposes. However, the pathological role of this
      receptor in GBM remains to be established. Here we report that IL-13Ralpha2 alone
      induces invasiveness of human GBM cells without affecting their proliferation. In
      contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13Ralpha2 promotes
      GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic
      domain of IL-13Ralpha2 specifically binds to EGFRvIII, and this binding
      upregulates the tyrosine kinase activity of EGFRvIII and activates the
      RAS/RAF/MEK/ERK and STAT3 pathways. Our findings support the "To Go or To Grow"
      hypothesis whereby IL-13Ralpha2 serves as a molecular switch from invasion to
      proliferation, and suggest that targeting both receptors with STAT3 signaling
      inhibitor might be a therapeutic approach for the treatment of GBM.

PMID- 29203860
TI  - Adipose tissue mitochondrial capacity associates with long-term weight loss
      success.
AB  - OBJECTIVES: We investigated whether (1) subcutaneous adipose tissue (SAT)
      mitochondrial capacity predicts weight loss success and (2) weight loss
      ameliorates obesity-related SAT mitochondrial abnormalities. METHODS: SAT
      biopsies were obtained from 19 clinically healthy obese subjects (body mass index
      (BMI) 34.6+/-2.7 kg m-2) during a weight loss intervention (0, 5 and 12 months)
      and from 19 lean reference subjects (BMI 22.7+/-1.1 kg m-2) at baseline. Based on
      1-year weight loss outcome, the subjects were divided into two groups: continuous
      weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures
      included SAT mitochondrial pathways from transcriptomics, mitochondrial amount
      (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts,
      oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the
      mitochondrial branched-chain amino-acid catabolism (BCAA) pathway. SAT and
      visceral adipose tissue (VAT) glucose uptake was measured with positron emission
      tomography. RESULTS: Despite similar baseline clinical characteristics, SAT in
      the WL group exhibited higher gene expression level of nuclear-encoded
      mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle,
      P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1
      (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline
      mitochondrial parameters correlated with WL success, and with SAT and VAT glucose
      uptake. During WL, the nuclear-encoded mitochondrial pathways were downregulated,
      together with increased plasma metabolite levels of BCAAs in both groups. MtDNA
      copy number increased in the WR group at 5 months (P=0.012), but decreased to
      baseline level between 5 and 12 months (P=0.015). The only significant change in
      the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The
      levels of Porin did not change in either group upon WL. CONCLUSIONS: Higher
      mitochondrial capacity in SAT predicts good long-term WL success. WL does not
      ameliorate SAT mitochondrial downregulation and based on pathway expression, may
      paradoxically further reduce it.Data availability:The transcriptomics data
      generated in this study have been deposited to the Gene Expression Omnibus public
      repository, accession number GSE103769.

PMID- 29203862
TI  - Diversification of human plasmacytoid predendritic cells in response to a single
      stimulus.
AB  - Innate immune cells adjust to microbial and inflammatory stimuli through a
      process termed environmental plasticity, which links a given individual stimulus
      to a unique activated state. Here, we report that activation of human
      plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine
      stimulus triggers cell diversification into three stable subpopulations (P1-P3).
      P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for
      type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic
      morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both
      innate and adaptive functions. Each subpopulation expressed a specific coding-
      and long-noncoding-RNA signature and was stable after secondary stimulation. P1
      pDCs were detected in samples from patients with lupus or psoriasis. pDC
      diversification was independent of cell divisions or preexisting heterogeneity
      within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine
      communication loop. Our findings reveal a novel mechanism for diversity and
      division of labor in innate immune cells.

PMID- 29203864
TI  - Van der Waals epitaxial growth and optoelectronics of large-scale WSe2/SnS2
      vertical bilayer p-n junctions.
AB  - High-quality two-dimensional atomic layered p-n heterostructures are essential
      for high-performance integrated optoelectronics. The studies to date have been
      largely limited to exfoliated and restacked flakes, and the controlled growth of
      such heterostructures remains a significant challenge. Here we report the direct
      van der Waals epitaxial growth of large-scale WSe2/SnS2 vertical bilayer p-n
      junctions on SiO2/Si substrates, with the lateral sizes reaching up to millimeter
      scale. Multi-electrode field-effect transistors have been integrated on a single
      heterostructure bilayer. Electrical transport measurements indicate that the
      field-effect transistors of the junction show an ultra-low off-state leakage
      current of 10-14 A and a highest on-off ratio of up to 107. Optoelectronic
      characterizations show prominent photoresponse, with a fast response time of 500
      MUs, faster than all the directly grown vertical 2D heterostructures. The direct
      growth of high-quality van der Waals junctions marks an important step toward
      high-performance integrated optoelectronic devices and systems.

PMID- 29203863
TI  - ORAI channels are critical for receptor-mediated endocytosis of albumin.
AB  - Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has
      been highlighted in diabetic nephropathy (DN), but little is known about the
      underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially
      expressed in PTECs and downregulated in patients with DN. Hyperglycemia or
      blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of
      ORAI channels by BTP2 and diethylstilbestrol or silencing of ORAI expression
      impairs albumin uptake. Transgenic mice expressing a dominant-negative Orai1
      mutant (E108Q) increases albuminuria, and in vivo injection of BTP2 exacerbates
      albuminuria in streptozotocin-induced and Akita diabetic mice. The albumin
      endocytosis is Ca2+-dependent and accompanied by ORAI1 internalization.
      Amnionless (AMN) associates with ORAIs and forms STIM/ORAI/AMN complexes after
      Ca2+ store depletion. STIM1/ORAI1 colocalizes with clathrin, but not with
      caveolin, at the apical membrane of PTECs, which determines clathrin-mediated
      endocytosis. These findings provide insights into the mechanisms of protein
      reabsorption and potential targets for treating diabetic proteinuria.

PMID- 29203866
TI  - Rpgrip1 is required for rod outer segment development and ciliary protein
      trafficking in zebrafish.
AB  - Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber
      congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod
      dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has
      been proposed to have a role in ciliary protein transport; however, its function
      remains elusive. Here, we describe a new zebrafish model carrying a nonsense
      mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer
      segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1
      in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of
      rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1
      mutants. The degeneration of rod cells is early onset, followed by the death of
      cone cells. These phenotypes are similar to that observed in LCA and juvenile RP
      patients. Our data indicate RPGRIP1 is necessary for rod outer segment
      development through regulating ciliary protein trafficking. The rpgrip1 mutant
      zebrafish may provide a platform for developing therapeutic treatments for RP
      patients.

PMID- 29203865
TI  - Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer
      immunotherapy.
AB  - Subunit vaccines have been investigated in over 1000 clinical trials of cancer
      immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy
      but have rarely been clinically translated. By conjugating molecular vaccines
      with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop
      clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo
      from AlbiVax and endogenous albumin for efficient vaccine delivery and potent
      cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and
      flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and
      antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete
      Freund's adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent
      peripheral antigen-specific CD8+ cytotoxic T lymphocytes with immune memory than
      IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of
      established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination
      with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates
      most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for
      combination cancer immunotherapy.

PMID- 29203868
TI  - A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate
      cancer risk and aggressiveness.
AB  - Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of
      two to six nucleotides. We hypothesized that STRs are associated with prostate
      cancer development and/or progression. We undertook RNA sequencing analysis of
      prostate tumors and adjacent non-malignant cells to identify polymorphic STRs
      that are readily expressed in these cells. Most of the expressed STRs in the
      clinical samples mapped to intronic and intergenic DNA. Our analysis indicated
      that three of these STRs (TAAA-ACTG2, TTTTG-TRIB1, and TG-PCA3) are polymorphic
      and differentially expressed in prostate tumors compared to adjacent non
      malignant cells. TG-PCA3 STR expression was repressed by the anti-androgen drug
      enzalutamide in prostate cancer cells. Genetic analysis of prostate cancer
      patients and healthy controls (N > 2,000) showed a significant association of the
      most common 11 repeat allele of TG-PCA3 STR with prostate cancer risk (OR = 1.49;
      95% CI 1.11-1.99; P = 0.008). A significant association was also observed with
      aggressive disease (OR = 2.00; 95% CI 1.06-3.76; P = 0.031) and high mortality
      rates (HR = 3.0; 95% CI 1.03-8.77; P = 0.045). We propose that TG-PCA3 STR has
      both diagnostic and prognostic potential for prostate cancer. We provided a proof
      of concept to be applied to other RNA sequencing datasets to identify disease
      associated STRs for future clinical exploratory studies.

PMID- 29203867
TI  - Sensory Stream Adaptation in Chaotic Networks.
AB  - Implicit expectations induced by predictable stimuli sequences affect neuronal
      response to upcoming stimuli at both single cell and neural population levels.
      Temporally regular sensory streams also phase entrain ongoing low frequency brain
      oscillations but how and why this happens is unknown. Here we investigate how
      random recurrent neural networks without plasticity respond to stimuli streams
      containing oddballs. We found the neuronal correlates of sensory stream
      adaptation emerge if networks generate chaotic oscillations which can be phase
      entrained by stimulus streams. The resultant activity patterns are close to
      critical and support history dependent response on long timescales. Because
      critical network entrainment is a slow process stimulus response adapts gradually
      over multiple repetitions. Repeated stimuli generate suppressed responses but
      oddball responses are large and distinct. Oscillatory mismatch responses persist
      in population activity for long periods after stimulus offset while individual
      cell mismatch responses are strongly phasic. These effects are weakened in
      temporally irregular sensory streams. Thus we show that network phase entrainment
      provides a biologically plausible mechanism for neural oddball detection. Our
      results do not depend on specific network characteristics, are consistent with
      experimental studies and may be relevant for multiple pathologies demonstrating
      altered mismatch processing such as schizophrenia and depression.

PMID- 29203869
TI  - TRPM7 kinase activity is essential for T cell colonization and alloreactivity in
      the gut.
AB  - The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a
      cation channel and a serine/threonine kinase, has been implicated in thymopoiesis
      and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant
      (Trpm7 R/R ) mice, that the enzymatic activity of the receptor is not essential
      for thymopoiesis, but is required for CD103 transcription and gut-homing of intra
      epithelial lymphocytes. Defective T cell gut colonization reduces MHCII
      expression in intestinal epithelial cells. Mechanistically, TRPM7 kinase activity
      controls TGF-beta-induced CD103 expression and pro-inflammatory T helper 17, but
      not regulatory T, cell differentiation by modulating SMAD2. Notably, we find that
      the TRPM7 kinase activity promotes gut colonization by alloreactive T cells in
      acute graft-versus-host disease. Thus, our results unravel a function of TRPM7
      kinase in T cell activity and suggest a therapeutic potential of kinase
      inhibitors in averting acute graft-versus-host disease.

PMID- 29203870
TI  - IFT proteins spatially control the geometry of cleavage furrow ingression and
      lumen positioning.
AB  - Cytokinesis mediates the physical separation of dividing cells and, in 3D
      epithelia, provides a spatial landmark for lumen formation. Here, we unravel an
      unexpected role in cytokinesis for proteins of the intraflagellar transport (IFT)
      machinery, initially characterized for their ciliary role and their link to
      polycystic kidney disease. Using 2D and 3D cultures of renal cells, we show that
      IFT proteins are required to correctly shape the central spindle, to control
      symmetric cleavage furrow ingression and to ensure central lumen positioning.
      Mechanistically, IFT88 directly interacts with the kinesin MKLP2 and is essential
      for the correct relocalization of the Aurora B/MKLP2 complex to the central
      spindle. IFT88 is thus required for proper centralspindlin distribution and
      central spindle microtubule organization. Overall, this work unravels a novel non
      ciliary mechanism for IFT proteins at the central spindle, which could contribute
      to kidney cyst formation by affecting lumen positioning.

PMID- 29203871
TI  - CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.
AB  - Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly
      discovered immunomodulator, has been confirmed to have a stronger
      immunoregulation than Propionibacterium acnes (P. acnes) of the traditional
      immune adjuvant, by previous experiments with model antigen ovalbumin and sheep
      red blood cells. Here, it was designed to assess its ability to resist
      methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram
      positive pathogen is characterized by high morbidity and mortality. In this
      report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN)
      could help to be against bloodstream infection of MRSA with raised survival rate,
      decreased bacteria load and alleviated systemic inflammation, and these effects
      of CP-PGN were more pronounced. However, the whole CP was inclined to prevent
      localized abdominal infection of MRSA from progressing to a systemic infection.
      And they showed the potential as a therapeutic drug alone or combined with
      vancomycin. The diversity of capacity of activating macrophages induced by CP and
      CP-PGN may result in distinct resistance to MRSA in different infection models.
      Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its
      PGN could act as promising immune agents to treat and prevent MRSA infection.

PMID- 29203872
TI  - DNA metabarcoding data unveils invisible pollination networks.
AB  - Animal pollination, essential for both ecological services and ecosystem
      functioning, is threatened by ongoing global changes. New methodologies to
      decipher their effects on pollinator composition to ecosystem health are urgently
      required. We compare the main structural parameters of pollination networks based
      on DNA metabarcoding data with networks based on direct observations of insect
      visits to plants at three resolution levels. By detecting numerous additional
      hidden interactions, metabarcoding data largely alters the properties of the
      pollination networks compared to visit surveys. Molecular data shows that
      pollinators are much more generalist than expected from visit surveys. However,
      pollinator species were composed of relatively specialized individuals and formed
      functional groups highly specialized upon floral morphs. We discuss pros and cons
      of metabarcoding data relative to data obtained from traditional methods and
      their potential contribution to both current and future research. This molecular
      method seems a very promising avenue to address many outstanding scientific
      issues at a resolution level which remains unattained to date; especially for
      those studies requiring pollinator and plant community investigations over macro
      ecological scales.

PMID- 29203873
TI  - Multiyne chains chelating osmium via three metal-carbon sigma bonds.
AB  - Although the formation of metal-carbon sigma bonds is a fundamental principle in
      organometallic chemistry, the direct bonding of one organic molecule with one
      metal center to generate more than two metal-carbon sigma bonds remains a
      challenge. Herein, we report an aromaticity-driven method whereby multiyne chains
      are used to construct three metal-carbon sigma bonds in a one-pot reaction under
      mild conditions. In this method, multiyne chains act as ligand precursors capable
      of chelating an osmium center to yield planar metallapolycycles, which exhibit
      aromaticity and good stability. The direct assembly of various multiyne chains
      with commercially available metal complexes or even simple metal salts provides a
      convenient and efficient strategy for constructing all carbon-ligated chelates on
      the gram scale.

PMID- 29203874
TI  - The Posterior Insula Shows Disrupted Brain Functional Connectivity in Female
      Migraineurs Without Aura Based on Brainnetome Atlas.
AB  - Long-term headache attacks may cause human brain network reorganization in
      patients with migraine. In the current study, we calculated the topologic
      properties of functional networks based on the Brainnetome atlas using graph
      theory analysis in 29 female migraineurs without aura (MWoA) and in 29 female age
      matched healthy controls. Compared with controls, female MWoA exhibited that the
      network properties altered, and the nodal centralities decreased/increased in
      some brain areas. In particular, the right posterior insula and the left medial
      superior occipital gyrus of patients exhibited significantly decreased nodal
      centrality compared with healthy controls. Furthermore, female MWoA exhibited a
      disrupted functional network, and notably, the two sub-regions of the right
      posterior insula exhibited decreased functional connectivity with many other
      brain regions. The topological metrics of functional networks in female MWoA
      included alterations in the nodal centrality of brain regions and disrupted
      connections between pair regions primarily involved in the discrimination of
      sensory features of pain, pain modulation or processing and sensory integration
      processing. In addition, the posterior insula decreased the nodal centrality, and
      exhibited disrupted connectivity with many other brain areas in female
      migraineurs, which suggests that the posterior insula plays an important role in
      female migraine pathology.

PMID- 29203875
TI  - The individual environment, not the family is the most important influence on
      preferences for common non-alcoholic beverages in adolescence.
AB  - Beverage preferences are an important driver of consumption, and strong liking
      for beverages high in energy (e.g. sugar-sweetened beverages [SSBs]) and dislike
      for beverages low in energy (e.g. non-nutritive sweetened beverages [NNSBs]) are
      potentially modifiable risk factors contributing to variation in intake. Twin
      studies have established that both genes and environment play important roles in
      shaping food preferences; but the aetiology of variation in non-alcoholic
      beverage preferences is unknown. 2865 adolescent twins (18-19-years old) from the
      Twins Early Development Study were used to quantify genetic and environmental
      influence on variation in liking for seven non-alcoholic beverages: SSBs; NNSBs;
      fruit cordials, orange juice, milk, coffee, and tea. Maximum Likelihood
      Structural Equation Modelling established that beverage preferences have a
      moderate to low genetic basis; from 18% (95% CI: 10%, 25%) for orange juice to
      42% (36%, 43%) for fruit cordials. Aspects of the environment that are not shared
      by twin pairs explained all remaining variance in drink preferences. The sizeable
      unique environmental influence on beverage preferences highlights the potential
      for environmental modification. Policies and guidelines to change preferences for
      unhealthy beverages may therefore be best directed at the wider environment.

PMID- 29203876
TI  - The relationship between personality and the response to acute psychological
      stress.
AB  - The present study examined the relationship between personality traits and the
      response to acute psychological stress induced by a standardized laboratory
      stress induction procedure (the Trier Social Stress Test, TSST). The stress
      response was measured with a combination of cardiovascular reactivity,
      hypothalamic-pituitary-adrenal axis reactivity, and subjective affect (including
      positive affect, negative affect and subjective controllability) in healthy
      individuals. The Generalized Estimating Equations (GEE) approach was applied to
      account for the relationship between personality traits and stress responses.
      Results suggested that higher neuroticism predicted lower heart rate stress
      reactivity, lower cortisol stress response, more decline of positive affect and
      lower subjective controllability. Individuals higher in extraversion showed
      smaller cortisol activation to stress and less increase of negative affect. In
      addition, higher openness score was associated with lower cortisol stress
      response. These findings elucidate that neuroticism, extraversion and openness
      are important variables associated with the stress response and different
      dimensions of personality trait are associated with different aspects of the
      stress response.

PMID- 29203877
TI  - Formation of carbyne-like materials during low temperature pyrolysis of
      lignocellulosic biomass: A natural resource of linear sp carbons.
AB  - The exploration, understanding and potential applications of 'Carbyne', the one
      dimensional sp allotrope of carbon, have been severely limited due to its extreme
      reactivity and a tendency for highly exothermic cross-linking. Due to ill-defined
      materials, limited characterization and a lack of compelling definitive evidence,
      even the existence of linear carbons has been questioned. We report a first-ever
      investigation on the formation of carbyne-like materials during low temperature
      pyrolysis of biobased lignin, a natural bioresource. The presence of carbyne was
      confirmed by detecting acetylenic -C=C- bonds in lignin chars using NMR, Raman
      and FTIR spectroscopies. The crystallographic structure of this phase was
      determined as hexagonal: a = 6.052 A, c = 6.96 A from x-ray diffraction results.
      HRSEM images on lignin chars showed that the carbyne phase was present as
      nanoscale flakes/fibers (~10 nm thick) dispersed in an organic matrix and showed
      no sign of overlapping or physical contact. These nanostructures did not show any
      tendency towards cross-linking, but preferred to branch out instead. Overcoming
      key issues/challenges associated with their formation and stability, this study
      presents a novel approach for producing a stable condensed phase of sp-bonded
      linear carbons from a low-cost, naturally abundant, and renewable bioresource.

PMID- 29203879
TI  - QuPath: Open source software for digital pathology image analysis.
AB  - QuPath is new bioimage analysis software designed to meet the growing need for a
      user-friendly, extensible, open-source solution for digital pathology and whole
      slide image analysis. In addition to offering a comprehensive panel of tumor
      identification and high-throughput biomarker evaluation tools, QuPath provides
      researchers with powerful batch-processing and scripting functionality, and an
      extensible platform with which to develop and share new algorithms to analyze
      complex tissue images. Furthermore, QuPath's flexible design makes it suitable
      for a wide range of additional image analysis applications across biomedical
      research.

PMID- 29203880
TI  - Evidence for a novel function of Awd in maintenance of genomic stability.
AB  - The abnormal wing discs (awd) gene encodes the Drosophila homolog of NME1/NME2
      metastasis suppressor genes. Awd acts in multiple tissues where its function is
      critical in establishing and maintaining epithelial integrity. Here, we analysed
      awd gene function in Drosophila epithelial cells using transgene-mediated RNA
      interference and genetic mosaic analysis. We show that awd knockdown in larval
      wing disc epithelium leads to chromosomal instability (CIN) and induces apoptosis
      mediated by activation of c-Jun N-terminal kinase. Forced maintenance of Awd
      depleted cells, by expressing the cell death inhibitor p35, downregulates
      atypical protein kinase C and DE-Cadherin. Consistent with their loss of cell
      polarity and enhanced level of matrix metalloproteinase 1, cells delaminate from
      wing disc epithelium. Furthermore, the DNA content profile of these cells
      indicates that they are aneuploid. Overall, our data demonstrate a novel function
      for awd in maintenance of genomic stability. Our results are consistent with
      other studies reporting that NME1 down-regulation induces CIN in human cell lines
      and suggest that Drosophila model could be successfully used to study in vivo the
      impact of NME/Awd - induced genomic instability on tumour development and
      metastasis formation.

PMID- 29203878
TI  - ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair
      pathway choice.
AB  - CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand
      break (DSB) repair. However, how it regulates this repair process is poorly
      understood. Here we uncover that CSB interacts via its newly identified winged
      helix domain with RIF1, an effector of 53BP1, and that this interaction mediates
      CSB recruitment to DSBs in S phase. At DSBs, CSB remodels chromatin by evicting
      histones, which limits RIF1 and its effector MAD2L2 but promotes BRCA1
      accumulation. The chromatin remodeling activity of CSB requires not only damage
      induced phosphorylation on S10 by ATM but also cell cycle-dependent
      phosphorylation on S158 by cyclin A-CDK2. Both modifications modulate the
      interaction of the CSB N-terminal region with its ATPase domain, the activity of
      which has been previously reported to be autorepressed by the N-terminal region.
      These results suggest that ATM and CDK2 control the chromatin remodeling activity
      of CSB in the regulation of DSB repair pathway choice.

PMID- 29203881
TI  - In vivo tropism of Salmonella Typhi toxin to cells expressing a multiantennal
      glycan receptor.
AB  - Typhoid fever is a life-threatening disease, but little is known about the
      molecular bases for its unique clinical presentation. Typhoid toxin, a unique
      virulence factor of Salmonella Typhi (the cause of typhoid fever), recapitulates
      in an animal model many symptoms of typhoid fever. Typhoid toxin binding to its
      glycan receptor Neu5Ac is central, but, due to the ubiquity of Neu5Ac, how
      typhoid toxin causes specific symptoms remains elusive. Here we show that typhoid
      toxin displays in vivo tropism to cells expressing multiantennal glycoprotein
      receptors, particularly on endothelial cells of arterioles in the brain and
      immune cells, which is in line with typhoid symptoms. Neu5Ac displayed by
      multiantennal N-glycans, rather than a single Neu5Ac, appears to serve as the
      high-affinity receptor, as typhoid toxin possesses five identical binding pockets
      per toxin. Human counterparts also express the multiantennal Neu5Ac receptor.
      Here we also show that mice immunized with inactive typhoid toxins and challenged
      with wild-type typhoid toxin presented neither the characteristic in vivo tropism
      nor symptoms. These mice were protected against a lethal-dose toxin challenge,
      but Ty21a-vaccinated mice were not. Cumulatively, these results reveal remarkable
      features describing how a bacterial exotoxin induces virulence exclusively in
      specific cells at the organismal level.

PMID- 29203882
TI  - PASTA repeats of the protein kinase StkP interconnect cell constriction and
      separation of Streptococcus pneumoniae.
AB  - Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats
      are key membrane regulators of bacterial cell division. How PASTA repeats govern
      eSTK activation and function remains elusive. Using evolution- and structural
      guided approaches combined with cell imaging, we disentangle the role of each
      PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three
      membrane-proximal PASTA repeats behave as interchangeable modules required for
      the activation of StkP independently of cell wall binding, they also control the
      septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA
      repeat directs StkP localization at the division septum and encompasses a
      specific motif that is critical for final cell separation through interaction
      with the cell wall hydrolase LytB. We propose a model in which the extracellular
      four-PASTA domain of StkP plays a dual function in interconnecting the
      phosphorylation of StkP endogenous targets along with septal cell wall
      remodelling to allow cell division of the pneumococcus.

PMID- 29203884
TI  - A homeostatic apical microtubule network shortens cells for epithelial folding
      via a basal polarity shift.
AB  - Epithelial folding is typically driven by localized actomyosin contractility.
      However, it remains unclear how epithelia deform when myosin levels are low and
      uniform. In the Drosophila gastrula, dorsal fold formation occurs despite a lack
      of localized myosin changes, while the fold-initiating cells reduce cell height
      following basal shifts of polarity via an unknown mechanism. We show that cell
      shortening depends on an apical microtubule network organized by the CAMSAP
      protein Patronin. Prior to gastrulation, microtubule forces generated by the
      minus-end motor dynein scaffold the apical cell cortex into a dome-like shape,
      while the severing enzyme Katanin facilitates network remodelling to ensure
      tissue-wide cell size homeostasis. During fold initiation, Patronin redistributes
      following basal polarity shifts in the initiating cells, apparently weakening the
      scaffolding forces to allow dome descent. The homeostatic network that ensures
      size/shape homogeneity is thus repurposed for cell shortening, linking epithelial
      polarity to folding via a microtubule-based mechanical mechanism.

PMID- 29203883
TI  - ABIN-1 regulates RIPK1 activation by linking Met1 ubiquitylation with Lys63
      deubiquitylation in TNF-RSC.
AB  - Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation
      of RIPK1, a kinase critically involved in mediating multiple TNFalpha-activated
      deleterious events. However, the molecular mechanism that coordinates different
      types of ubiquitylation modification to regulate the activation of RIPK1 kinase
      remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is
      recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating
      complex LUBAC to regulate the recruitment of A20 to control Lys63
      deubiquitylation of RIPK1. ABIN-1 deficiency reduces the recruitment of A20 and
      licenses cells to die through necroptosis by promoting Lys63 ubiquitylation and
      activation of RIPK1 with TNFalpha stimulation under conditions that would
      otherwise exclusively activate apoptosis in wild-type cells. Inhibition of RIPK1
      kinase and RIPK3 deficiency block the embryonic lethality of Abin-1 -/- mice. We
      propose that ABIN-1 provides a critical link between Met1 ubiquitylation mediated
      by the LUBAC complex and Lys63 deubiquitylation by phospho-A20 to modulate the
      activation of RIPK1.

PMID- 29203885
TI  - Monocyte gene expression in childhood obesity is associated with obesity and
      complexity of atherosclerosis in adults.
AB  - Childhood obesity coincides with increased numbers of circulating classical
      CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in
      the development and exacerbation of atherosclerosis, which prompts the question
      as to whether the monocytosis in childhood obesity contributes to atherogenesis
      over the years. Here, we dissected the monocyte gene expression profile in
      childhood obesity using an Illumina microarray platform on sorted monocytes of 35
      obese children and 16 lean controls. Obese children displayed a distinctive
      monocyte gene expression profile compared to lean controls. Upon validation with
      quantitative PCR, we studied the association of the top 5 differentially
      regulated monocyte genes in childhood obesity with obesity and complexity of
      coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for
      ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and
      TMEM134 in childhood obesity was also observed in obese adults. Moreover,
      downregulation of monocyte TMEM134 was associated with a higher SYNTAX
      atherosclerosis score in adults. In conclusion, childhood obesity entails
      monocyte gene expression alterations associated with obesity and enhanced
      complexity of coronary atherosclerosis in adults.

PMID- 29203886
TI  - Transcriptomic profiling of the human brain reveals that altered synaptic gene
      expression is associated with chronological aging.
AB  - Aging is a biologically universal event, and yet the key events that drive aging
      are still poorly understood. One approach to generate new hypotheses about aging
      is to use unbiased methods to look at change across lifespan. Here, we have
      examined gene expression in the human dorsolateral frontal cortex using RNA- Seq
      to populate a whole gene co-expression network analysis. We show that modules of
      co-expressed genes enriched for those encoding synaptic proteins are liable to
      change with age. We extensively validate these age-dependent changes in gene
      expression across several datasets including the publically available GTEx
      resource which demonstrated that gene expression associations with aging vary
      between brain regions. We also estimated the extent to which changes in cellular
      composition account for age associations and find that there are independent
      signals for cellularity and aging. Overall, these results demonstrate that there
      are robust age-related alterations in gene expression in the human brain and that
      genes encoding for neuronal synaptic function may be particularly sensitive to
      the aging process.

PMID- 29203887
TI  - Age-dependent increase of oxidative stress regulates microRNA-29 family
      preserving cardiac health.
AB  - The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model
      for aging studies. Here, we investigated its age-associated cardiac function. We
      observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in
      the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40
      week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with
      age. MiR-29 family turned out as one of the most up-regulated miRNAs during
      aging. MiR-29 family increase induces a decrease of known targets like collagens
      and DNA methyl transferases (DNMTs) paralleled by 5'methyl-cytosine (5mC) level
      decrease. To further investigate miR-29 family role in the fish heart we
      generated a transgenic zebrafish model where miR-29 was knocked-down. In this
      model we found significant morphological and functional cardiac alterations and
      an impairment of oxygen dependent pathways by transcriptome analysis leading to
      hypoxic marker up-regulation. To get insights the possible hypoxic regulation of
      miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic
      condition we found miR-29 down-modulation responsible for the accumulation of
      collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation
      might represent an endogenous mechanism aimed at ameliorating the age-dependent
      cardiac damage leading to hypertrophy and fibrosis.

PMID- 29203888
TI  - Insight into the molecular recognition mechanism of the coactivator NCoA1 by
      STAT6.
AB  - Crucial for immune and anti-inflammatory cellular responses, signal transducer
      and activator of transcription 6 (STAT6) regulates transcriptional activation in
      response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct
      interaction with coactivators. The interaction of STAT6 with nuclear coactivator
      1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that
      includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite
      the availability of an X-ray structure of the PAS-B domain/ Leu794-Gly814-STAT6
      complex, the mechanistic details of this interaction are still poorly understood.
      Here, we determine the structure of the NCoA1257-385/STAT6783-814 complex using
      Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6783-814
      peptide binds with additional N-terminal amino acids to NCoA1257-385, compared to
      the STAT6794-814 peptide, explaining its higher affinity. Secondary and tertiary
      structures existing in the free peptide are more highly populated in the complex,
      suggesting binding by conformational selection.

PMID- 29203889
TI  - Single-molecule imaging reveals dimerization/oligomerization of CXCR4 on plasma
      membrane closely related to its function.
AB  - Dimerization and oligomerization of G-protein coupled receptors (GPCRs) have
      emerged as important characters during their trans-membrane signal transduction.
      However, until now the relationship between GPCR dimerization and their trans
      membrane signal transduction function is still uncovered. Here, using pertussis
      toxin (PTX) to decouple the receptor from G protein complex and with single
      molecule imaging, we show that in the presence of agonist, cells treated with PTX
      showed a decrease in the number of dimers and oligomers on the cell surface
      compared with untreated ones, which suggests that oligomeric status of CXCR4
      could be significantly influenced by the decoupling of G protein complex during
      its signal transduction process. Moreover, with chlorpromazine (CPZ) to inhibit
      internalization of CXCR4, it was found that after SDF-1alpha stimulation, cells
      treated with CPZ showed more dimers and oligomers on the cell surface than
      untreated ones, which suggest that dimers and oligomers of CXCR4 tend to
      internalize more easily than monomers. Taken together, our results demonstrate
      that dimerization and oligomerization of CXCR4 is closely related with its G
      protein mediated pathway and beta-arrestin mediated internalization process, and
      would play an important role in regulating its signal transduction functions.

PMID- 29203890
TI  - Increased pollinator service and reduced pollen limitation in the fixed dune
      populations of a desert shrub.
AB  - Evaluations of restoration success usually focus on the structural aspects of
      ecosystems. Pollination, as an important functional aspect, is often overlooked.
      Here, the shifts in pollinator assemblage and pollen limitation in the desert
      shrub Caragana microphylla were examined along a restoration gradient in Horqin
      Sand Land, northern China. We identified seven species of bees; however, only
      four bee species were found to be effective pollinators, with Xanthosaurus remota
      dominating in the fixed dunes, and with no bee species or only a single species,
      X. remota, being observed in the semi-fixed and mobile dunes. Flower visitation
      rate was nearly ten times higher in the fixed dunes than in the mobile and semi
      fixed dunes. Experimental floral manipulations revealed that the fixed dune
      populations experienced less pollen limitation, along with the increase in
      pollinator availability. Between the mobile and semi-fixed dune populations,
      pollen limitation was severe and at similar levels. The intensity of pollen
      limitation was negatively related to pollinator abundance and richness. Overall,
      the dependence on pollinators for reproduction may be an important constraint
      that limits persistence in this system. Increased pollinator service during the
      restoration process may ameliorate pollen limitation, benefiting the restoration
      of vegetation in this semiarid sandy area.

PMID- 29203891
TI  - Deep mutational scanning of S. pyogenes Cas9 reveals important functional
      domains.
AB  - RNA-guided endonucleases (RGENs) have invigorated the field of site-specific
      nucleases. The success of Streptococcus pyogenes Cas9 (SpCas9) has led to the
      discovery of several other CRISPR-associated RGENs. As more RGENs become
      available, it will be necessary to refine their activity before they can be
      translated into the clinic. With this in mind, we sought to demonstrate how deep
      mutational scanning (DMS) could provide details about important functional
      regions in SpCas9 and speed engineering efforts. Consequently, we developed a
      nuclease screening platform which could distinguish active Cas9 mutants. We
      screened a library of 1.9 * 107 with over 8500 possible non-synonymous mutations
      and inferred the effects of each mutation using DMS. We demonstrate that the RuvC
      and HNH domains are the least tolerant regions to mutation. In contrast, the Rec2
      and PI domains tolerate mutation better than other regions. The mutation
      information defined in this work provides a foundation for further SpCas9
      engineering. Together, our results demonstrate how DMS can be a powerful tool to
      uncover features important to RGEN function. Application of this approach to
      emerging RGENs should enhance their engineering and optimization for therapeutic
      and other applications.

PMID- 29203892
TI  - Metabolic syndrome and smoking are associated with an increased risk of nocturia
      in male patients with benign prostatic enlargement.
AB  - BACKGROUND: To evaluate the relationship between cigarette smoking, metabolic
      syndrome (MetS) and nocturia in patients with lower urinary tract symptoms (LUTS)
      and benign prostatic enlargement (BPE). METHODS: From 2009 onward, a consecutive
      series of patients with LUTS/BPE were enrolled. Symptoms were assessed using the
      International Prostate Symptom Score (IPSS). Age, body mass index (BMI), smoker
      status, prostate volume (PV), prostate-specific antigen (PSA) levels, fasting
      glucose levels, triglyceride levels, and high-density lipoprotein levels were
      recorded. MetS was defined according to Adult Treatment Panel III criteria.
      Moderate/severe nocturia was defined as nocturnal micturition episodes >=2.
      RESULTS: Overall 492 patients were enrolled with median age and BMI of 68 years
      (IQR 61/74) and 26.5 kg/m2 (IQR: 24/29), respectively. Moderate/severe nocturia
      was reported in 212 (43.1%) patients. MetS was diagnosed in 147 (29.9%) patients
      and out of them 89 (60.5%) complained moderate/severe nocturia (p = 0.001).
      Overall 187 (38%) patients were current smokers and out of them 99 (52%)
      presented moderate/severe nocturia(p = 0.034). Patients with moderate/severe
      nocturia were older (p = 0.001) and with larger prostate volume (p = 0.003). On
      multivariate analysis, age (OR: 1.067 per year, 95% CI: 1.036-1.098; p = 0.001),
      PV (OR: 1.011 per ml, 95% CI: 1.003-1.019; p = 0.006), MetS (OR: 2.509, 95% CI:
      1.571-4.007; p = 0.001) and smoking (OR: 1.690, 95% CI: 1.061-2.693; p = 0.027)
      were associated with nocturia severity. CONCLUSIONS: MetS and smoking doubled the
      risk of moderate/severe nocturia in patients with LUTS and BPE. Assessing smoking
      and metabolic status in LUTS/ BPE patients is suggested.

PMID- 29203895
TI  - Baseline prostate atrophy is associated with lower tumor volume in men with
      prostate cancer on repeat biopsy.
AB  - BACKGROUND: Prostate atrophy (PA) is commonly identified in prostate biopsies.
      Previous studies suggest PA may be associated with lower PCa risk. However, it
      remains unclear whether PA is associated with smaller, less aggressive, and less
      advanced tumors. Thus, we sought to determine whether the presence and severity
      of baseline PA in men with initial biopsy negative for prostate cancer (PCa) is
      associated with PCa volume at 2- and 4-year repeat biopsy. METHODS: We performed
      a retrospective analysis of 927 men 50-75-years-old with negative baseline biopsy
      and positive 2- or 4-year repeat biopsy for PCa in the Reduction by Dutasteride
      of PCa Events study. PA (present or absent), PA severity (mild or
      moderate/marked), and tumor volume were determined by central pathology. The
      association of baseline PA with repeat biopsy PCa volume was evaluated with
      linear and Poisson regressions in uni- and multivariable analyses. RESULTS: PA
      was identified in 559 (60%) baseline biopsies and was mild in 491 (88%) and
      moderate/marked in 68 (12%). PA was associated with larger prostate volumes (P <
      0.001). At 2-year biopsy, PA was associated with lower overall mean total tumor
      volume (2.21 vs. 2.94 uL; P = 0.016), mean number of biopsy cores involved (1.85
      vs. 2.08; P = 0.016), mean percent of cores involved (18.4% vs. 20.7%; P =
      0.008), average core involvement (0.23 vs. 0.29 uL; P = 0.019) and overall mean
      percent tumor involvement (1.82% vs. 2.33%; P = 0.018). Similar results were
      found in multivariable analysis and analysis of 4-year repeat biopsies. Compared
      to mild PA, moderate/marked PA was associated with greater reduction in tumor
      volume. CONCLUSION: Amongst subjects with repeat prostate biopsy positive for PCa
      after negative baseline biopsy, the presence and severity of baseline PA were
      associated with lower PCa volume. This suggests PA may be associated with less
      aggressive PCa.

PMID- 29203894
TI  - Combining intratumoral Treg depletion with androgen deprivation therapy (ADT):
      preclinical activity in the Myc-CaP model.
AB  - BACKGROUND: Immune checkpoint blockade has shown promising antitumor activity
      against a variety of tumor types. However, responses in castration-resistant
      prostate cancer remain relatively rare-potentially due to low baseline levels of
      infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought to
      understand the immune infiltrate induced by androgen deprivation therapy (ADT)
      and to leverage that infiltration toward therapeutic benefit. METHODS: Using flow
      cytometry, qPCR and IHC, we quantified ADT-induced immune infiltration in terms
      of cell type and function. Preclinical treatment studies tested the combinatorial
      effects of ADT and immune checkpoint blockade using tumor outgrowth and overall
      survival as end points. RESULTS: ADT induces a complex pro-inflammatory
      infiltrate. This pro-inflammatory infiltrate was apparent in the early
      postcastration period but diminished as castration resistance emerged. Combining
      ADT with tumor-infiltrating regulatory T cell (Treg) depletion using a depleting
      anti-CTLA-4 antibody significantly delayed the development of castration
      resistance and prolonged survival of a fraction of tumor-bearing mice.
      Immunotherapy as a monotherapy failed to provide a survival benefit and was
      ineffective if not administered in the peri-castration period. CONCLUSIONS: The
      immune infiltrate induced by ADT is diverse and varies over time. Therapeutic
      strategies focusing on depleting Tregs in the peri-castration period are of
      particular interest.

PMID- 29203893
TI  - Phase II prospective randomized trial of weight loss prior to radical
      prostatectomy.
AB  - BACKGROUND: Obesity is associated with poorly differentiated and advanced
      prostate cancer and increased mortality. In preclinical models, caloric
      restriction delays prostate cancer progression and prolongs survival. We sought
      to determine if weight loss (WL) in men with prostate cancer prior to radical
      prostatectomy affects tumor apoptosis and proliferation, and if WL effects other
      metabolic biomarkers. METHODS: In this Phase II prospective trial, overweight and
      obese men scheduled for radical prostatectomy were randomized to a 5-8 week WL
      program consisting of standard structured energy-restricted meal plans (1200-1500
      Kcal/day) and physical activity or to a control group. The primary endpoint was
      apoptotic index in the radical prostatectomy malignant epithelium. Secondary
      endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body
      weight, body mass index (BMI), waist to hip ratio, body composition, and serum
      PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin,
      adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF
      binding protein 1. RESULTS: In total 23 patients were randomized to the WL
      intervention and 21 patients to the control group. Subjects in the intervention
      group had significantly more weight loss (WL:-3.7 +/- 0.5 kg; Control:-1.6 +/-
      0.5 kg; p = 0.007) than the control group and total fat mass was significantly
      reduced (WL:-2.1 +/- 0.4; Control: 0.1 +/- 0.3; p = 0.015). There was no
      significant difference in apoptotic or proliferation index between the groups.
      Among the other biomarkers, triglyceride, and insulin levels were significantly
      decreased in the WL compared with the control group. CONCLUSIONS: In summary,
      this short-term WL program prior to radical prostatectomy resulted in
      significantly more WL in the intervention vs. the control group and was
      accompanied by significant reductions in body fat mass, circulating
      triglycerides, and insulin. However, no significant changes were observed in
      malignant epithelium apoptosis or proliferation. Future studies should consider a
      longer term or more intensive weight loss intervention.

PMID- 29203896
TI  - Proteomic analysis of postsynaptic proteins in regions of the human neocortex.
AB  - The postsynaptic proteome of excitatory synapses comprises ~1,000 highly
      conserved proteins that control the behavioral repertoire, and mutations
      disrupting their function cause >130 brain diseases. Here, we document the
      composition of postsynaptic proteomes in human neocortical regions and integrate
      it with genetic, functional and structural magnetic resonance imaging, positron
      emission tomography imaging, and behavioral data. Neocortical regions show
      signatures of expression of individual proteins, protein complexes, biochemical
      and metabolic pathways. We characterized the compositional signatures in brain
      regions involved with language, emotion and memory functions. Integrating large
      scale GWAS with regional proteome data identifies the same cortical region for
      smoking behavior as found with fMRI data. The neocortical postsynaptic proteome
      data resource can be used to link genetics to brain imaging and behavior, and to
      study the role of postsynaptic proteins in localization of brain functions.

PMID- 29203897
TI  - Flexible timing by temporal scaling of cortical responses.
AB  - Musicians can perform at different tempos, speakers can control the cadence of
      their speech, and children can flexibly vary their temporal expectations of
      events. To understand the neural basis of such flexibility, we recorded from the
      medial frontal cortex of nonhuman primates trained to produce different time
      intervals with different effectors. Neural responses were heterogeneous,
      nonlinear, and complex, and they exhibited a remarkable form of temporal
      invariance: firing rate profiles were temporally scaled to match the produced
      intervals. Recording from downstream neurons in the caudate and from thalamic
      neurons projecting to the medial frontal cortex indicated that this phenomenon
      originates within cortical networks. Recurrent neural network models trained to
      perform the task revealed that temporal scaling emerges from nonlinearities in
      the network and that the degree of scaling is controlled by the strength of
      external input. These findings demonstrate a simple and general mechanism for
      conferring temporal flexibility upon sensorimotor and cognitive functions.

PMID- 29203898
TI  - An interactive framework for whole-brain maps at cellular resolution.
AB  - To deconstruct the architecture and function of brain circuits, it is necessary
      to generate maps of neuronal connectivity and activity on a whole-brain scale.
      New methods now enable large-scale mapping of the mouse brain at cellular and
      subcellular resolution. We developed a framework to automatically annotate,
      analyze, visualize and easily share whole-brain data at cellular resolution,
      based on a scale-invariant, interactive mouse brain atlas. This framework enables
      connectivity and mapping projects in individual laboratories and across imaging
      platforms, as well as multiplexed quantitative information on the molecular
      identity of single neurons. As a proof of concept, we generated a comparative
      connectivity map of five major neuron types in the corticostriatal circuit, as
      well as an activity-based map to identify hubs mediating the behavioral effects
      of cocaine. Thus, this computational framework provides the necessary tools to
      generate brain maps that integrate data from connectivity, neuron identity and
      function.

PMID- 29203899
TI  - 661W is a retinal ganglion precursor-like cell line in which glaucoma-associated
      optineurin mutants induce cell death selectively.
AB  - A photoreceptor cell line, 661W, derived from a mouse retinal tumor that
      expresses several markers of cone photoreceptor cells has been described earlier.
      However, these cells can be differentiated into neuronal cells. Here, we report
      that this cell line expressed certain markers specific to retinal ganglion cells
      such as Rbpms, Brn3b (Pou4f2), Brn3c (Pou4f3), Thy1 and gamma-synuclein (Sncg),
      and some other markers of neuronal cells (beta-III tubulin, NeuN and MAP2). These
      cells also expressed Opn1mw, a cone-specific marker and nestin, a marker for
      neural precursor cells. Two glaucoma-associated mutants of OPTN, E50K and M98K,
      but not an amyotrophic lateral sclerosis-associated mutant, E478G, induced cell
      death selectively in 661W cells. However, in a motor neuron cell line, NSC34,
      E478G mutant of OPTN but not E50K and M98K induced cell death. We conclude that
      661W is a retinal ganglion precursor-like cell line, which shows properties of
      both retinal ganglion and photoreceptor cells. We suggest that these cells could
      be utilized for exploring the mechanisms of cell death induction and
      cytoprotection relevant for glaucoma pathogenesis. RGC-5 cell line which probably
      arose from 661W cells showed expression of essentially the same markers of
      retinal ganglion cells and neuronal cells as seen in 661W cells.

PMID- 29203901
TI  - Seismogenesis of dual subduction beneath Kanto, central Japan controlled by fluid
      release.
AB  - Dual subduction represents an unusual case of subduction where one oceanic plate
      subducts on top of another, creating a highly complex tectonic setting. Because
      of the complex interaction between the two subducted plates, the origin of
      seismicity in such region is still not fully understood. Here we investigate the
      thermal structure of dual subduction beneath Kanto, central Japan formed as a
      consequence of a unique case of triple trench junction. Using high-resolution
      three-dimensional thermo-mechanical models tailored for the specific dual
      subduction settings beneath Kanto, we show that, compared with single-plate
      subduction systems, subduction of double slabs produces a strong variation of
      mantle flow, thermal and fluid release pattern that strongly controls the
      regional seismicity distribution. Here the deepening of seismicity in the Pacific
      slab located under the Philippine Sea slab is explained by delaying at greater
      depths (~150 km depth) of the eclogitization front in this region. On the other
      hand, the shallower seismicity observed in the Philippine Sea slab is related to
      a young and warm plate subduction and probably to the presence of a hot mantle
      flow traveling underneath the slab and then moving upward on top of the slab.

PMID- 29203900
TI  - Intracellular immunization against HIV infection with an intracellular antibody
      that mimics HIV integrase binding to the cellular LEDGF protein.
AB  - Preventing the protein-protein interaction of the cellular chromatin binding
      protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency
      virus (HIV) integrase is an important possible strategy for anti-viral treatment
      for AIDS. We have used Intracellular Antibody Capture technology to isolate a
      single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF
      VH complex reveals that the single domain antibody mimics the effect of binding
      of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T
      cell lines were constructed to constitutively express the LEDGF-binding VH and
      these cells showed interference with HIV viral replication, assayed by virus
      capsid protein p24 production. Therefore, pre-conditioning cells to express
      antibody fragments confers effective intracellular immunization for preventing
      chronic viral replication and can be a way to prevent HIV spread in infected
      patients. This raises the prospect that intracellular immunization strategies
      that focus on cellular components of viral integrase protein interactions can be
      used to combat the problems associated with latent HIV virus re-emergence in
      patients. New genome editing development, such as using CRISPR/cas9, offer the
      prospect intracellularly immunized T cells in HIV+ patients.

PMID- 29203902
TI  - Amniotic fluid stem cell-derived vesicles protect from VEGF-induced endothelial
      damage.
AB  - Injection of amniotic fluid stem cells (AFSC) delays the course of progression of
      renal fibrosis in animals with Alport Syndrome, enhancing kidney function and
      improving survival. The mechanisms responsible for these protective outcomes are
      still largely unknown. Here, we showed that vascular endothelial growth factor
      (VEGF) signaling within the glomeruli of Alport mice is strongly elevated early
      on in the disease, causing glomerular endothelial cell damage. Intraventricular
      injected AFSC that homed within the glomeruli showed strong modulation of the
      VEGF activity, particularly in glomerular endothelial cells. To investigate this
      phenomenon we hypothesized that extracellular vesicles (EVs) produced by the AFSC
      could be responsible for the observed renoprotection. AFSC derived EVs presented
      exosomal and stem cell markers on their surface membrane, including VEGFR1 and
      VEGFR2. EVs were able to modulate VEGF in glomerular endothelial cells by
      effectively trapping the excess VEGF through VEGFR1-binding preventing cellular
      damage. In contrast, VEGFR1/sVEGFR1 knockout EVs failed to show similar
      protection, thus indicating that VEGF trapping is a potentially viable mechanism
      for AFSC-EV mediated renoprotection. Taken together, our findings establish that
      EVs secreted by AFSC could target a specific signaling pathway within the
      glomerulus, thus representing a new potential glomerulus-specific targeted
      intervention.

PMID- 29203903
TI  - Structures of PPARgamma complexed with lobeglitazone and pioglitazone reveal key
      determinants for the recognition of antidiabetic drugs.
AB  - Peroxisome proliferator-activator receptor (PPAR) gamma is a nuclear hormone
      receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte
      function. PPARgamma is a target for thiazolidinedione (TZD) class of drugs which
      are widely used for the treatment of type 2 diabetes. Recently, lobeglitazone was
      developed as a highly effective TZD with reduced side effects by Chong Kun Dang
      Pharmaceuticals. To identify the structural determinants for the high potency of
      lobeglitazone as a PPARgamma agonist, we determined the crystal structures of the
      PPARgamma ligand binding domain (LBD) in complex with lobeglitazone and
      pioglitazone at 1.7 and 1.8 A resolutions, respectively. Comparison of ligand
      bound PPARgamma structures revealed that the binding modes of TZDs are well
      conserved. The TZD head group forms hydrogen bonds with the polar residues in the
      AF-2 pocket and helix 12, stabilizing the active conformation of the LBD. The
      unique p-methoxyphenoxy group of lobeglitazone makes additional hydrophobic
      contacts with the Omega-pocket. Docking analysis using the structures of TZD
      bound PPARgamma suggested that lobeglitazone displays 12 times higher affinity to
      PPARgamma compared to rosiglitazone and pioglitazone. This structural difference
      correlates with the enhanced affinity and the low effective dose of lobeglitazone
      compared to the other TZDs.

PMID- 29203904
TI  - Spatial blurring in laser speckle imaging in inhomogeneous turbid media.
AB  - Laser speckle imaging (LSI) has developed into a versatile tool to image
      dynamical processes in turbid media, such as subcutaneous blood perfusion and
      heterogeneous dynamics in soft materials. Spatially resolved information about
      local dynamics is obtained by measuring time-dependent correlation functions of
      multiply scattered light. Due to the diffusive nature of photons in highly
      scattering media, the measured signal is a convolution of the local dynamics in
      the material and the spatial distribution of photons. This spatial averaging
      inevitably leads to a loss of resolution, which must be taken into account for a
      correct interpretation of LSI measurements. In this paper we derive analytical
      expressions to quantify the effects of spatial blurring in backscatter LSI for
      materials with heterogeneous dynamics. Using the diffusion approximation, we
      calculate the photon density distribution for a semi-infinite material, and we
      predict the effect of dynamic heterogeneity on the measured correlation function.
      We verify our theoretical expressions using random walk simulations. Our results
      show that LSI measurements in dynamically heterogeneous materials should be
      interpreted with caution, especially when only a single wavelength and
      correlation time are used to obtain the dynamical map.

PMID- 29203905
TI  - Rainbow trout exposed to benzo[a]pyrene yields conserved microRNA binding sites
      in DNA methyltransferases across 500 million years of evolution.
AB  - The objective of this study was to examine the regulation of DNA methylation
      following acute (24 h) and prolonged (14 d) exposure to low (1 ng/L) and high (10
      ng/L) benzo[a]pyrene. However, with the recent release of the rainbow trout
      genome, we were able to conduct a more detailed analysis regarding the regulation
      of the enzymes involved in DNA methylation; DNA methyltransferases (DNMTs).
      Bioinformatic approaches were used to identify candidate microRNA (miRNA) that
      potentially bind to the DNMT1 and DNMT3a 3'UTR. Results indicated a significant
      decrease in global methylation in both liver and muscle, with an associated
      decrease in DNA methyltransferase activity and DNMT3a transcript abundance. There
      was a significant increase in one specific candidate miRNA (miR29a) that was
      predicted to bind to DNMT3a. Taking a comparative genomics approach, the binding
      sites of miR29a to the DNMT3a 3'UTR was compared across species, spanning fish to
      mammals, and revealed a highly conserved binding motif that has been maintained
      since the vertebrate ancestor, approximately 500 million years ago. This research
      establishes that miRNA act as an essential mediator between the environment and
      DNA methylation patterns via DNMTs, which is further confirmed by a genomic
      regulatory mechanism that has been deeply conserved throughout evolution.

PMID- 29203906
TI  - Hydrothermal treatment and butylphosphonic acid derived self-assembled monolayers
      for improving the surface chemistry and corrosion resistance of AZ61 magnesium
      alloy.
AB  - The hydrothermal treatment followed by a self-assembled monolayer (SAM) of 1
      butylphosphonic acid through the tethering by aggregation and growth (T-BAG)
      method was employed to produce protective surface coatings on the Mg-6Al-1Zn
      alloy (AZ61) for reducing the degradation rate in physiological environments.
      Potentiodynamic polarization measurements revealed that the organic self
      assembled monolayer and Mg(OH)2 coating can further enhance the surface chemical
      stability and corrosion resistance of Mg alloys. SAM-treated Mg(OH)2 coatings can
      be served as a more passive surface layer as a result of their much higher charge
      transfer resistance and the presence of Warburg impedance in electrochemical
      impedance spectroscopy measurement.

PMID- 29203907
TI  - The sensitivity and stability of bacterioplankton community structure to wind
      wave turbulence in a large, shallow, eutrophic lake.
AB  - Lakes are strongly influenced by wind-driven wave turbulence. The direct physical
      effects of turbulence on bacterioplankton community structure however, have not
      yet been addressed and remains poorly understood. To examine the stability of
      bacterioplankton communities under turbulent conditions, we simulated conditions
      in the field to evaluate the responses of the bacterioplankton community to
      physical forcing in Lake Taihu, using high-throughput sequencing and flow
      cytometry. A total of 4,520,231 high quality sequence reads and 74,842 OTUs were
      obtained in all samples with alpha-proteobacteria, gamma-proteobacteria and
      Actinobacteria being the most dominant taxa. The diversity and structure of
      bacterioplankton communities varied during the experiment, but were highly
      similar based on the same time of sampling, suggesting that bacterioplankton
      communities are insensitive to wind wave turbulence in the lake. This stability
      could be associated with the traits associated with bacteria. In particular,
      turbulence favored the growth of bacterioplankton, which enhanced biogeochemical
      cycling of nutrients in the lake. This study provides a better understanding of
      bacterioplankton communities in lake ecosystems exposed to natural
      mixing/disturbances.

PMID- 29203908
TI  - Relationship between body mass and ambulatory blood pressure: comparison with
      office blood pressure measurement and effect of treatment.
AB  - Epidemiologic studies assessing the relationship between blood pressure (BP),
      body mass, and cardiovascular events have primarily been based on office BP
      measurements, and few data are available in the elderly. The aim of the present
      study was to evaluate the relationship between body mass index (BMI) and BP
      values obtained by ambulatory blood pressure monitoring (ABPM) as compared to
      office BP measurements, and the effect of anti-hypertensive treatment on the
      relationship. The study population consisted of 813 subjects participating in the
      cardiovascular abnormalities and brain lesions (CABL) study who underwent 24-h
      ABPM. Office BP (mean of two measurements) was found to be associated with
      increasing BMI, for both SBP (p <= 0.05) and DBP (p <= 0.001). In contrast, there
      was no association seen of increasing BMI with ABPM parameters in the overall
      cohort, even after adjusting for age and gender. However, among subjects not on
      anti-hypertensive treatment, office SBP and DBP measurements were significantly
      correlated with increasing BMI (p <= 0.01) as were daytime SBP and 24-h SBP,
      although with a smaller spread across BMI subgroups compared with office
      readings. In treated hypertensives, there was only a trend toward increasing
      office DBP and increasing DBP variability with higher BMI. Our results suggest
      that body mass may have a less significant influence on BP values in the elderly
      when ABPM rather than office measurements are considered, particularly in
      patients receiving anti-hypertensive treatment.

PMID- 29203909
TI  - Dynamic epigenomic landscapes during early lineage specification in mouse
      embryos.
AB  - In mammals, all somatic development originates from lineage segregation in early
      embryos. However, the dynamics of transcriptomes and epigenomes acting in concert
      with initial cell fate commitment remains poorly characterized. Here we report a
      comprehensive investigation of transcriptomes and base-resolution methylomes for
      early lineages in peri- and postimplantation mouse embryos. We found allele
      specific and lineage-specific de novo methylation at CG and CH sites that led to
      differential methylation between embryonic and extraembryonic lineages at
      promoters of lineage regulators, gene bodies, and DNA-methylation valleys. By
      using Hi-C experiments to define chromatin architecture across the same
      developmental period, we demonstrated that both global demethylation and
      remethylation in early development correlate with chromatin compartments. Dynamic
      local methylation was evident during gastrulation, which enabled the
      identification of putative regulatory elements. Finally, we found that de novo
      methylation patterning does not strictly require implantation. These data reveal
      dynamic transcriptomes, DNA methylomes, and 3D chromatin landscapes during the
      earliest stages of mammalian lineage specification.

PMID- 29203911
TI  - A synthetic lethal bullet.

PMID- 29203910
TI  - TET proteins safeguard bivalent promoters from de novo methylation in human
      embryonic stem cells.
AB  - TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC),
      which can lead to DNA demethylation. However, direct connections between TET
      mediated DNA demethylation and transcriptional output are difficult to establish
      owing to challenges in distinguishing global versus locus-specific effects. Here
      we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells
      (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall
      corresponding decrease in gene expression in the undifferentiated state. Focusing
      on the bivalent PAX6 locus, we find that increased DNMT3B binding is associated
      with promoter hypermethylation, which precipitates a neural differentiation
      defect and failure of PAX6 induction during differentiation. dCas9-mediated locus
      specific demethylation and global inactivation of DNMT3B in TKO hESCs partially
      reverses the hypermethylation at the PAX6 promoter and improves differentiation
      to neuroectoderm. Taking these findings together with further genome-wide
      methylation and TET1 and DNMT3B ChIP-seq analyses, we conclude that TET proteins
      safeguard bivalent promoters from de novo methylation to ensure robust lineage
      specific transcription upon differentiation.

PMID- 29203912
TI  - Bacterial resistance to silver nanoparticles and how to overcome it.
AB  - Silver nanoparticles have already been successfully applied in various biomedical
      and antimicrobial technologies and products used in everyday life. Although
      bacterial resistance to antibiotics has been extensively discussed in the
      literature, the possible development of resistance to silver nanoparticles has
      not been fully explored. We report that the Gram-negative bacteria Escherichia
      coli 013, Pseudomonas aeruginosa CCM 3955 and E. coli CCM 3954 can develop
      resistance to silver nanoparticles after repeated exposure. The resistance stems
      from the production of the adhesive flagellum protein flagellin, which triggers
      the aggregation of the nanoparticles. This resistance evolves without any genetic
      changes; only phenotypic change is needed to reduce the nanoparticles' colloidal
      stability and thus eliminate their antibacterial activity. The resistance
      mechanism cannot be overcome by additional stabilization of silver nanoparticles
      using surfactants or polymers. It is, however, strongly suppressed by inhibiting
      flagellin production with pomegranate rind extract.

PMID- 29203913
TI  - Humidity-controlled rectification switching in ruthenium-complex molecular
      junctions.
AB  - Although molecular rectifiers were proposed over four decades ago 1,2 , until
      recently reported rectification ratios (RR) were rather moderate 2-11 (RR ~ 101).
      This ceiling was convincingly broken using a eutectic GaIn top contact 12 to
      probe molecular monolayers of coupled ferrocene groups (RR ~ 105), as well as
      using scanning tunnelling microscopy-break junctions 13-16 and mechanically
      controlled break junctions 17 to probe single molecules (RR ~ 102-103). Here, we
      demonstrate a device based on a molecular monolayer in which the RR can be
      switched by more than three orders of magnitude (between RR ~ 100 and RR >= 103)
      in response to humidity. As the relative humidity is toggled between 5% and 60%,
      the current-voltage (I-V) characteristics of a monolayer of di-nuclear Ru-complex
      molecules reversibly change from symmetric to strongly asymmetric (diode-like).
      Key to this behaviour is the presence of two localized molecular orbitals in
      series, which are nearly degenerate in dry circumstances but become misaligned
      under high humidity conditions, due to the displacement of counter ions (PF6-).
      This asymmetric gating of the two relevant localized molecular orbital levels
      results in humidity-controlled diode-like behaviour.

PMID- 29203915
TI  - Thermoelectric spin voltage in graphene.
AB  - In recent years, new spin-dependent thermal effects have been discovered in
      ferromagnets, stimulating a growing interest in spin caloritronics, a field that
      exploits the interaction between spin and heat currents 1,2 . Amongst the most
      intriguing phenomena is the spin Seebeck effect 3-5 , in which a thermal gradient
      gives rise to spin currents that are detected through the inverse spin Hall
      effect 6-8 . Non-magnetic materials such as graphene are also relevant for spin
      caloritronics, thanks to efficient spin transport 9-11 , energy-dependent carrier
      mobility and unique density of states 12,13 . Here, we propose and demonstrate
      that a carrier thermal gradient in a graphene lateral spin valve can lead to a
      large increase of the spin voltage near to the graphene charge neutrality point.
      Such an increase results from a thermoelectric spin voltage, which is analogous
      to the voltage in a thermocouple and that can be enhanced by the presence of hot
      carriers generated by an applied current 14-17 . These results could prove
      crucial to drive graphene spintronic devices and, in particular, to sustain pure
      spin signals with thermal gradients and to tune the remote spin accumulation by
      varying the spin-injection bias.

PMID- 29203914
TI  - Synthetically lethal nanoparticles for treatment of endometrial cancer.
AB  - Uterine serous carcinoma, one of the most aggressive types of endometrial cancer,
      is characterized by poor outcomes and mutations in the tumour suppressor p53. Our
      objective was to engender synthetic lethality to paclitaxel (PTX), the frontline
      treatment for endometrial cancer, in tumours with mutant p53 and enhance the
      therapeutic efficacy using polymeric nanoparticles (NPs). First, we identified
      the optimal NP formulation through comprehensive analyses of release profiles and
      cellular-uptake and cell viability studies. Not only were PTX-loaded NPs superior
      to PTX in solution, but the combination of PTX-loaded NPs with the antiangiogenic
      molecular inhibitor BIBF 1120 (BIBF) promoted synthetic lethality specifically in
      cells with the loss-of-function (LOF) p53 mutation. In a xenograft model of
      endometrial cancer, this combinatorial therapy resulted in a marked inhibition of
      tumour progression and extended survival. Together, our data provide compelling
      evidence for future studies of BIBF- and PTX-loaded NPs as a therapeutic
      opportunity for LOF p53 cancers.

PMID- 29203916
TI  - A model for 'sustainable' US beef production.
AB  - Food production dominates land, water and fertilizer use and is a greenhouse gas
      source. In the United States, beef production is the main agricultural resource
      user overall, as well as per kcal or g of protein. Here, we offer a possible, non
      unique, definition of 'sustainable' beef as that subsisting exclusively on grass
      and by-products, and quantify its expected US production as a function of
      pastureland use. Assuming today's pastureland characteristics, all of the
      pastureland that US beef currently use can sustainably deliver ~45% of current
      production. Rewilding this pastureland's less productive half (~135 million ha)
      can still deliver ~43% of current beef production. In all considered scenarios,
      the ~32 million ha of high-quality cropland that beef currently use are
      reallocated for plant-based food production. These plant items deliver 2- to 20
      fold more calories and protein than the replaced beef and increase the delivery
      of protective nutrients, but deliver no B12. Increased deployment of rapid
      rotational grazing or grassland multi-purposing may increase beef production
      capacity.

PMID- 29203917
TI  - Foraging constraints reverse the scaling of activity time in carnivores.
AB  - The proportion of time an animal spends actively foraging in a day determines its
      long-term fitness. Here, we derive a general mathematical model for the scaling
      of this activity time with body size in consumers. We show that this scaling can
      change from positive (increasing with size) to negative (decreasing with size) if
      the detectability and availability of preferred prey sizes is a limiting factor.
      These predictions are supported by a global dataset on 73 terrestrial carnivore
      species from 8 families spanning >3 orders of magnitude in size. Carnivores
      weighing ~5 kg experience high foraging costs because their diets include
      significant proportions of relatively small (invertebrate) prey. As a result,
      they show an increase in activity time with size. This shifts to a negative
      scaling in larger carnivores as they shift to foraging on less costly vertebrate
      prey. Our model can be generalized to other classes of terrestrial and aquatic
      consumers and offers a general framework for mechanistically linking body size to
      population fitness and vulnerability in consumers.

PMID- 29203918
TI  - The beef with sustainability.

PMID- 29203919
TI  - Climatic niche shifts are common in introduced plants.
AB  - Our understanding of how climate influences species distributions and our ability
      to assess the risk of introduced species depend on the assumption that species'
      climatic niches remain stable across space and time. While niche shifts have been
      detected in individual invasive species, one assessment of ~50 plants in Europe
      and North America concluded that niche shifts were rare, while another concluded
      the opposite. These contradictory findings, limited in species number and
      geographic scope, leave open a need to understand how often introduced species
      experience niche shifts and whether niche shifts can be predicted. We found
      evidence of climatic niche shifts in 65-100% of 815 terrestrial plant species
      introduced across five continents, depending on how niche shifts were measured.
      Individual species responses were idiosyncratic, but we generally saw that niche
      shifts reflected changes in climate availability at the continent scale and were
      largest in long-lived and cultivated species. Smaller intercontinental niche
      shifts occurred within species' native ranges. Overall, the climatic niches of
      terrestrial plant species were not conserved as they crossed continents. These
      results have major consequences for applying environmental niche models to assess
      the risk of invasive species and for predicting species responses to climate
      change. Our findings challenge the tenet that species' niches are conserved
      aspects of their ecology.

PMID- 29203921
TI  - The ecological importance of intraspecific variation.
AB  - Human activity is causing wild populations to experience rapid trait change and
      local extirpation. The resulting effects on intraspecific variation could have
      substantial consequences for ecological processes and ecosystem services.
      Although researchers have long acknowledged that variation among species
      influences the surrounding environment, only recently has evidence accumulated
      for the ecological importance of variation within species. We conducted a meta
      analysis comparing the ecological effects of variation within a species
      (intraspecific effects) with the effects of replacement or removal of that
      species (species effects). We evaluated direct and indirect ecological responses,
      including changes in abundance (or biomass), rates of ecological processes and
      changes in community composition. Our results show that intraspecific effects are
      often comparable to, and sometimes stronger than, species effects. Species
      effects tend to be larger for direct ecological responses (for example, through
      consumption), whereas intraspecific effects and species effects tend to be
      similar for indirect responses (for example, through trophic cascades).
      Intraspecific effects are especially strong when indirect interactions alter
      community composition. Our results summarize data from the first generation of
      studies examining the relative ecological effects of intraspecific variation. Our
      conclusions can help inform the design of future experiments and the formulation
      of strategies to quantify and conserve biodiversity.

PMID- 29203920
TI  - Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against
      transposable elements.
AB  - In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence
      transposable elements (TEs), protecting the germline from genomic instability and
      mutation. piRNAs have been detected in the soma in a few animals, but these are
      believed to be specific adaptations of individual species. Here, we report that
      somatic piRNAs were probably present in the ancestral arthropod more than 500
      million years ago. Analysis of 20 species across the arthropod phylum suggests
      that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods.
      The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs,
      spiders and scorpions) suggests that arthropods originally used a plant-like RNA
      interference mechanism to silence TEs. Our results call into question the view
      that the ancestral role of the piRNA pathway was to protect the germline and
      demonstrate that small RNA silencing pathways have been repurposed for both
      somatic and germline functions throughout arthropod evolution.

PMID- 29203923
TI  - Social polymorphism is favoured by the co-evolution of dispersal with social
      behaviour.
AB  - Dispersal determines gene flow among groups in a population and so plays a major
      role in many ecological and evolutionary processes. As gene flow shapes kin
      structure, dispersal is important to the evolution of social behaviours that
      influence reproduction within groups. Conversely, dispersal depends on kin
      structure and social behaviour. Dispersal and social behaviour therefore co
      evolve, but the nature and consequences of this interplay are not well
      understood. Here, we show that it readily leads to the emergence of two social
      morphs: a sessile, benevolent morph expressed by individuals who tend to increase
      the reproduction of others within their group relative to their own; and a
      dispersive, self-serving morph expressed by individuals who tend to increase
      their own reproduction. This social polymorphism arises due to a positive linkage
      between the loci responsible for dispersal and social behaviour, leading to
      benevolent individuals preferentially interacting with relatives and self-serving
      individuals with non-relatives. We find that this linkage is favoured under a
      large spectrum of conditions, suggesting that associations between dispersal and
      other social traits should be common in nature. In line with this prediction,
      dispersers across a wide range of organisms have been reported to differ in their
      social tendencies from non-dispersers.

PMID- 29203922
TI  - Local loss and spatial homogenization of plant diversity reduce ecosystem
      multifunctionality.
AB  - Biodiversity is declining in many local communities while also becoming
      increasingly homogenized across space. Experiments show that local plant species
      loss reduces ecosystem functioning and services, but the role of spatial
      homogenization of community composition and the potential interaction between
      diversity at different scales in maintaining ecosystem functioning remains
      unclear, especially when many functions are considered (ecosystem
      multifunctionality). We present an analysis of eight ecosystem functions measured
      in 65 grasslands worldwide. We find that more diverse grasslands-those with both
      species-rich local communities (alpha-diversity) and large compositional
      differences among localities (beta-diversity)-had higher levels of
      multifunctionality. Moreover, alpha- and beta-diversity synergistically affected
      multifunctionality, with higher levels of diversity at one scale amplifying the
      contribution to ecological functions at the other scale. The identity of species
      influencing ecosystem functioning differed among functions and across local
      communities, explaining why more diverse grasslands maintained greater
      functionality when more functions and localities were considered. These results
      were robust to variation in environmental drivers. Our findings reveal that plant
      diversity, at both local and landscape scales, contributes to the maintenance of
      multiple ecosystem services provided by grasslands. Preserving ecosystem
      functioning therefore requires conservation of biodiversity both within and among
      ecological communities.

PMID- 29203924
TI  - Nemertean and phoronid genomes reveal lophotrochozoan evolution and the origin of
      bilaterian heads.
AB  - Nemerteans (ribbon worms) and phoronids (horseshoe worms) are closely related
      lophotrochozoans-a group of animals including leeches, snails and other
      invertebrates. Lophotrochozoans represent a superphylum that is crucial to our
      understanding of bilaterian evolution. However, given the inconsistency of
      molecular and morphological data for these groups, their origins have been
      unclear. Here, we present draft genomes of the nemertean Notospermus geniculatus
      and the phoronid Phoronis australis, together with transcriptomes along the adult
      bodies. Our genome-based phylogenetic analyses place Nemertea sister to the group
      containing Phoronida and Brachiopoda. We show that lophotrochozoans share many
      gene families with deuterostomes, suggesting that these two groups retain a core
      bilaterian gene repertoire that ecdysozoans (for example, flies and nematodes)
      and platyzoans (for example, flatworms and rotifers) do not. Comparative
      transcriptomics demonstrates that lophophores of phoronids and brachiopods are
      similar not only morphologically, but also at the molecular level. Despite
      dissimilar head structures, lophophores express vertebrate head and neuronal
      marker genes. This finding suggests a common origin of bilaterian head
      patterning, although different heads evolved independently in each lineage.
      Furthermore, we observe lineage-specific expansions of innate immunity and toxin
      related genes. Together, our study reveals a dual nature of lophotrochozoans,
      where conserved and lineage-specific features shape their evolution.

PMID- 29203925
TI  - Publisher Correction: Ecological and evolutionary approaches to managing honeybee
      disease.
AB  - In the HTML version of this Review originally published, a technical error led to
      the images in Box 2 being swapped over. This was corrected on 28 August 2017.

PMID- 29203927
TI  - Author Correction: Generation of convergent light beams by using surface plasmon
      locked Smith-Purcell radiation.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29203926
TI  - Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic
      cell death.
AB  - The risk of emerging pandemic influenza A viruses (IAVs) that approach the
      devastating 1918 strain motivates finding strain-specific host-pathogen
      mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting
      cells that activate T cells, linking innate to adaptive immunity. DC infection
      with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces
      global RNA degradation. Here, we show that DC infection with seasonal IAV causes
      immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic
      DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV,
      enhance maturation of uninfected DC and T cell proliferation. In vivo,
      circulating T cell levels are reduced after pandemic, but not seasonal, IAV
      infection. Using recombinant viruses, we identify the HA genomic segment as the
      mediator of cell death inhibition. These results show how pandemic influenza
      viruses subvert the immune response.

PMID- 29203928
TI  - Author Correction: Differential electron emission from polycyclic aromatic
      hydrocarbon molecules under fast ion impact.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29203929
TI  - Foraging and recruitment hotspot dynamics for the largest Atlantic loggerhead
      turtle rookery.
AB  - Determining patterns of migratory connectivity for highly-mobile, wide-ranging
      species, such as sea turtles, is challenging. Here, we combined satellite
      telemetry and stable isotope analysis to estimate foraging locations for 749
      individual loggerheads nesting along the east central Florida (USA) coast, the
      largest rookery for the Northwest Atlantic population. We aggregated individual
      results by year, identified seven foraging hotspots and tracked these summaries
      to describe the dynamics of inter-annual contributions of these geographic areas
      to this rookery over a nine-year period. Using reproductive information for a
      subset of turtles (n = 513), we estimated hatchling yields associated with each
      hotspots. We found considerable inter-annual variability in the relative
      contribution of foraging areas to the nesting adults. Also reproductive success
      differed among foraging hotspots; females using southern foraging areas laid
      nests that produced more offspring in all but one year of the study. These
      analyses identified two high priority areas for future research and conservation
      efforts: the continental shelf adjacent to east central Florida and the Great
      Bahama Bank, which support higher numbers of foraging females that provide higher
      rates of hatchling production. The implementation of the continuous-surface
      approach to determine geographic origins of unknown migrants is applicable to
      other migratory species.

PMID- 29203930
TI  - Downregulation of liver-intestine cadherin enhances cisplatin-induced apoptosis
      in human gastric cancer BGC823 cells.
AB  - Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin
      (CDH17) has been found to be involved in the proliferation and apoptosis of
      gastric cancer cells. Cisplatin is one of the most widely used antineoplastic
      agents in the treatment of solid tumor and hematological malignancies. However,
      the mechanism of enhancing cisplatin-inducing effects on human gastric cancer
      BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be
      clarified. In this study, we investigated the signaling pathway by which
      cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823
      cells. Our results indicate that down-expression of CDH17 gene can enhance
      apoptosis-inducing effects of cisplatin on human gastric cancer BGC823 cells. The
      expression levels of Bax and Cyt-c proteins were upregulated, but the expression
      levels of Bcl-2 and Bcl-xL proteins were downregulated by blocking CDH17 gene in
      gastric cancer BGC823 cells after treatment with cisplatin. Moreover, down
      expression of CDH17 enhanced the efficacy of cisplatin-induced inhibition of
      tumor growth in nude mice via apoptosis induction. Down-expression of CDH17 gene
      can significantly improve apoptosis-inducing effects of cisplatin in vitro and in
      vivo, which is a new strategy to improve chemotherapeutic effects on gastric
      cancer.

PMID- 29203931
TI  - Focusing light through scattering media by polarization modulation based
      generalized digital optical phase conjugation.
AB  - Optical scattering prevents light from being focused through thick biological
      tissue at depths greater than ~1 mm. To break this optical diffusion limit,
      digital optical phase conjugation (DOPC) based wavefront shaping techniques are
      being actively developed. Previous DOPC systems employed spatial light modulators
      that modulated either the phase or the amplitude of the conjugate light field.
      Here, we achieve optical focusing through scattering media by using polarization
      modulation based generalized DOPC. First, we describe an algorithm to extract the
      polarization map from the measured scattered field. Then, we validate the
      algorithm through numerical simulations and find that the focusing contrast
      achieved by polarization modulation is similar to that achieved by phase
      modulation. Finally, we build a system using an inexpensive twisted nematic
      liquid crystal based spatial light modulator (SLM) and experimentally demonstrate
      light focusing through 3-mm thick chicken breast tissue. Since the polarization
      modulation based SLMs are widely used in displays and are having more and more
      pixel counts with the prevalence of 4 K displays, these SLMs are inexpensive and
      valuable devices for wavefront shaping.

PMID- 29203934
TI  - Veterinary Medical Ethics.

PMID- 29203933
TI  - One health and a new Canadian vet school?

PMID- 29203935
TI  - Viral enteritis in calves.
AB  - A complex community of bacteria, viruses, fungi, protists, and other
      microorganisms inhabit the gastrointestinal tract of calves and play important
      roles in gut health and disease. The viral component of the microbiome (the
      virome) is receiving increasing attention for its role in neonatal calf diarrhea
      (NCD). Rotavirus and coronavirus have for a long time been associated with NCD
      and commercial vaccines have been produced against these agents. Recently,
      several other viruses which may play a role in diarrhea have been discovered in
      calf fecal samples, mostly by sequence-based methods. These viruses include
      torovirus, norovirus, nebovirus, astrovirus, kobuvirus, and enterovirus. Most
      studies have involved epidemiologic investigations seeking to show association
      with diarrhea for each virus alone or in combination with potential pathogens.
      However, determining the contribution of these viruses to calf diarrhea has been
      challenging and much uncertainty remains concerning their roles as primary
      pathogens, co-infection agents, or commensals.

PMID- 29203936
TI  - Incidence of gastric dilatation-volvulus following a splenectomy in 238 dogs.
AB  - There is contradicting information in the veterinary literature regarding canine
      splenectomy and the increased risk for subsequent gastric dilatation-volvulus.
      The main purpose of this study was to determine the rate of occurrence of gastric
      dilatation-volvulus following splenectomy in medium to large breed dogs compared
      with a control group undergoing other abdominal procedures. Follow-up was
      performed by reviewing the medical records and conducting phone interviews.
      Weight, gender, and presence of a hemoabdomen at the time of surgery were not
      significantly associated with occurrence of gastric dilatation-volvulus, while
      increasing age was. Ten of 238 (4%) dogs in the splenectomy group and 3/209
      (1.4%) dogs in the control group subsequently developed gastric dilatation
      volvulus, which was not significantly different (P = 0.08). While the findings
      approach significance and support a need for future investigation, the current
      recommendation for gastropexy at time of splenic removal should be made on a case
      by case basis and while considering previously documented risk factors.

PMID- 29203937
TI  - Comparison of surgical time and complication rate of subcutaneous and skin
      closure using barbed suture or traditional knotted suture in dogs.
AB  - This prospective study evaluated the handling, intraoperative and postoperative
      complication rates of a barbed knotless suture for closure of subcutaneous tissue
      and skin in 17 client-owned dogs (group A) following a tibial plateau leveling
      osteotomy procedure. Clinical characteristics, surgical time, and complication
      rates were compared to a control group of 17 client-owned dogs (group B) with
      subcutaneous tissue and skin closure using traditional suture material.
      Signalment was not significantly different between groups and did not have an
      effect on complication rates. Surgical times were not significantly different for
      subcutaneous tissue or skin closure between the 2 groups. There were
      significantly more intraoperative complications in the barbed suture group (A:
      4/17; B: 0/17; P = 0.033) but no difference in minor or major postoperative
      complication rates (minor A: 2/16; B: 1/14; P = 0.626, major A: 2/16; B: 0/14; P
      = 0.171).

PMID- 29203938
TI  - Short-term effects of dietary supplementation with amino acids in dogs with
      proteinuric chronic kidney disease.
AB  - This retrospective study investigated the impact of amino acid supplementation on
      body weight, serum albumin, creatinine and urea concentrations, and urine protein
      to-creatinine (UPC) ratio in proteinuric dogs with chronic kidney disease (CKD).
      Forty-six client-owned azotemic dogs with spontaneous proteinuric CKD already on
      a renal diet and in therapy with enalapril were included. After approximately 1
      month of treatment (baseline), 29 dogs received oral amino acid supplementation
      daily (group A) and 17 dogs did not (group B). The parameters under investigation
      were determined at baseline and after 4 to 8 weeks in both groups. Compared to
      baseline, body weight and serum albumin increased (P < 0.01, P < 0.05,
      respectively) at follow-up in group A, but did not change in group B. Serum
      creatinine concentration did not change in both groups; urea concentration (P <
      0.05) and UPC ratio (P < 0.01) decreased in group B, but not in group A.
      Supplementation with amino acids increased body weight and serum albumin
      concentration in these dogs but it might have prevented a decrease in proteinuria
      and urea concentration.

PMID- 29203939
TI  - A retrospective study of owner-requested testing as surveillance for equine
      infectious anemia in Canada (2009-2012).
AB  - This retrospective study was undertaken to estimate i) the surveillance coverage
      for equine infectious anemia (EIA) based on owner-requested testing, and ii) the
      incidence of case detection from this surveillance activity to inform a review of
      Canada's national disease control strategy. Based on sample submissions by
      accredited veterinarians to laboratories CFIA-approved for EIA testing between
      2009 and 2012, the estimated national surveillance coverage was 14% for all
      years, and 72 cases of EIA were detected. The annual national incidence of EIA
      detection ranged from 0.03 to 0.08 cases/1000 horses. On average, a greater
      proportion of the horse population was tested in eastern Canada (32%) than in
      western Canada (6%, P < 0.0001). The cumulative incidence of EIA detection was
      higher in western Canada (0.25 cases/1000 horses) than in eastern Canada (0.02
      cases/1000 horses, P < 0.0001). This study identified regional differences in
      owner-requested EIA testing and case detection resulting from this testing
      activity.

PMID- 29203940
TI  - Effects of probiotic VSL#3 on glomerular filtration rate in dogs affected by
      chronic kidney disease: A pilot study.
AB  - The aim of this study was to evaluate the effects of probiotic VSL#3 on
      glomerular filtration rate (GFR) in dogs affected by chronic kidney disease
      (CKD). The treatment group (n = 30) received prescription renal diet and
      probiotic VSL#3 (112 to 225 * 109 lyophilized bacteria per 10 kg body weight, PO,
      q24h for 2 months); the control group (n = 30) received prescription renal diet
      and standard therapy. All dogs underwent GFR measurement at the beginning of the
      study (T0) and were re-evaluated by GFR measurement after 2 months (T1). The GFR
      was significantly higher (P = 0.0001) in the treatment group compared to the
      control group at T1. In the treatment group, the GFR was significantly higher (P
      = 0.0008) at T1 compared to T0. In the control group, the GFR was significantly
      lower (P = 0.001) at T1 compared to T0. VSL#3 supplementation seemed to be
      efficient in reducing deterioration of GFR over time in dogs affected by CKD.

PMID- 29203941
TI  - Atypical hypocalcemia in 2 dairy cows, after having been fed discarded vegetable
      cooking oil.
AB  - Two mid-lactation dairy cows were presented sternally recumbent 4 days after the
      herd had been fed discarded vegetable cooking oil ad libitum. In both affected
      animals hypocalcemia was confirmed by clinical chemistry and response to
      treatment. This atypical presentation of hypocalcemia associated with feeding
      discarded cooking oil is previously unreported.

PMID- 29203942
TI  - Inguinal herniation of a mineralized paraprostatic cyst in a dog.
AB  - A firm mass was noted in the right inguinal subcutaneous region of an 11-year-old
      intact male Labrador retriever dog presented for right pelvic limb weakness.
      Pelvic radiographs showed 2 large ovoid structures with circumferential thin
      eggshell-like mineralization in the right external inguinal region. The
      structures were confirmed sonographically, and on magnetic resonance imaging as a
      large folded herniated mineralized paraprostatic cyst through a defect in the
      right inguinal wall. To the author's knowledge, this is the first published
      report of an inguinal herniated mineralized paraprostatic cyst.

PMID- 29203944
TI  - One Health and the expansion of veterinary education and practice in Canada.

PMID- 29203943
TI  - Severe upper airway obstruction following bilateral ventral bulla osteotomy in a
      cat.
AB  - A cat that underwent bilateral ventral bulla osteotomy (VBO) for treatment of
      otitis media and otitis interna secondary to bilateral inflammatory polyps,
      developed upper airway obstruction (UAO) soon after tracheal extubation. The cat
      was re-intubated but the UAO did not resolve at the next extubation. Eventually,
      tracheostomy was performed. Upper airway obstruction is a potential postoperative
      complication of bilateral VBO in cats.

PMID- 29203945
TI  - Is there an application for wireless capsule endoscopy in horses?
AB  - This pilot study assessed wireless capsule endoscopy in horses. Image
      transmission was achieved with good image quality. Time to exit the stomach was
      variable and identified as one limitation, together with gaps in image
      transmission, capsule tumbling, and inability to accurately locate the capsule.
      Findings demonstrate usefulness and current limitations.

PMID- 29203946
TI  - Unusual case of pyometra in a bichon frise dog.
AB  - An intact female bichon frise dog with anorexia and chronic vaginal discharge,
      was clinically diagnosed with an open pyometra upon workup and
      ovariohysterectomy. Two cystic structures were identified protruding from the
      uterine body and the wall appeared thickened. Histopathology revealed pyometra,
      cystic endometria hyperplasia, and adenomyosis with squamous metaplasia.

PMID- 29203947
TI  - Human-animal emotional contagion and client communication.

PMID- 29203948
TI  - Optimal detection of weak positive latent dependence between two sequences of
      multiple tests.
AB  - It is frequently of interest to jointly analyze two paired sequences of multiple
      tests. This paper studies the problem of detecting whether there are more pairs
      of tests that are significant in both sequences than would be expected by chance.
      The asymptotic detection boundary is derived in terms of parameters such as the
      sparsity of non-null cases in each sequence, the effect sizes of the signals, and
      the magnitude of the dependence between the two sequences. A new test for
      detecting weak dependence is also proposed, shown to be asymptotically adaptively
      optimal, studied in simulations, and applied to study genetic pleiotropy in 10
      pediatric autoimmune diseases.

PMID- 29203949
TI  - Simultaneous Wireless Power Transfer and Data Communication Using Synchronous
      Pulse-Controlled Load Modulation.
AB  - Wireless Power Transfer (WPT) and wireless data communication are both important
      problems of research with various applications, especially in medicine. However,
      these two problems are usually studied separately. In this work, we present a
      joint study of both problems. Most medical electronic devices, such as smart
      implants, must have both a power supply to allow continuous operation and a
      communication link to pass information. Traditionally, separate wireless channels
      for power transfer and communication are utilized, which complicate the system
      structure, increase power consumption and make device miniaturization difficult.
      A more effective approach is to use a single wireless link with both functions of
      delivering power and passing information. We present a design of such a wireless
      link in which power and data travel in opposite directions. In order to
      aggressively miniaturize the implant and reduce power consumption, we eliminate
      the traditional multi-bit Analog-to-Digital Converter (ADC), digital memory and
      data transmission circuits all together. Instead, we use a pulse stream, which is
      obtained from the original biological signal, by a sigma-delta converter and an
      edge detector, to alter the load properties of the WPT channel. The resulting WPT
      signal is synchronized with the load changes therefore requiring no memory
      elements to record inter-pulse intervals. We take advantage of the high
      sensitivity of the resonant WPT to the load change, and the system dynamic
      response is used to transfer each pulse. The transient time of the WPT system is
      analyzed using the coupling mode theory (CMT). Our experimental results show that
      the memoryless approach works well for both power delivery and data transmission,
      providing a new wireless platform for the design of future miniaturized medical
      implants.

PMID- 29203950
TI  - Self-management program participation and social support in Parkinson's disease:
      Mixed methods evaluation.
AB  - Aims: To explore the potential influence of the Stanford Chronic Disease Self
      Management Program (CDSMP) on social support in Parkinson disease (PD). Methods:
      This was a quasi-experimental mixed methods design. Volunteers with PD (n=27) and
      care partners (n=6) completed the CDSMP, questionnaires of social support and
      self-management outcomes, and an interview about social support in relation to
      CDSMP participation. PD participants (n=19) who did not participate in the CDSMP
      completed the questionnaires for quantitative comparison purposes. Results:
      Regarding the quantitative data, there were no significant effects of CDSMP
      participation on social support questionnaire scores; however, there were some
      positive correlations between changes in social support and changes in self
      management outcomes from pre- to post-CDSMP participation. Three qualitative
      themes emerged from the interviews: lack of perceived change in amount and
      quality of social support, positive impact on existing social networks, and
      benefit from participating in a supportive PD community. Conclusions: Although
      participants did not acknowledge major changes in social support, there were some
      social support-related benefits of CDSMP participation for PD participants and
      care partners. These findings provide a starting point for more in-depth studies
      of social support and self-management in this population.

PMID- 29203952
TI  - Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle
      immunogenicity on primary and metastatic cancer.
AB  - Although there is long association of medical hyperthermia and immune
      stimulation, the relative lack of a quantifiable and reproducible effect has
      limited the utility and advancement of this relationship in preclinical/clinical
      cancer and non-cancer settings. Recent cancer-based immune findings (immune
      checkpoint modulators etc.) including improved mechanistic understanding and
      biological tools now make it possible to modify and exploit the immune system to
      benefit conventional cancer treatments such as radiation and hyperthermia. Based
      on the prior experience of our research group including; cancer-based heat
      therapy, magnetic nanoparticle (mNP) hyperthermia, radiation biology, cancer
      immunology and Cowpea Mosaic Virus that has been engineered to over express
      antigenic proteins without RNA or DNA (eCPMV/VLP). This research was designed to
      determine if and how the intra-tumoral delivery of mNP hyperthermia and VLP can
      work together to improve local and systemic tumor treatment efficacy. Using the
      C3H mouse/MTG-B mammary adenocarcinoma cell model and the C57-B6 mouse/B-16-F10
      melanoma cancer cell model, our data suggests the appropriate combination of
      intra-tumoral mNP heat (e.g. 43 degrees C/30-60 minutes) and VLP (100 MUg/200 mm3
      tumor) not only result in significant primary tumor regression but the creation a
      systemic immune reaction that has the potential to retard secondary tumor growth
      (abscopal effect) and resist tumor rechallenge. Molecular data from these
      experiments suggest treatment based cell damage and immune signals such as Heat
      Shock Protein (HSP) 70/90, calreticulin, MTA1 and CD47 are potential targets that
      can be exploited to enhance the local and systemic (abscopal effect) immune
      potential of hyperthermia cancer treatment.

PMID- 29203951
TI  - Hypo-fractionated Radiation, Magnetic Nanoparticle Hyperthermia and a Viral
      Immunotherapy Treatment of Spontaneous Canine Cancer.
AB  - It has recently been shown that cancer treatments such as radiation and
      hyperthermia, which have conventionally been viewed to have modest immune based
      anti-cancer effects, may, if used appropriately stimulate a significant and
      potentially effective local and systemic anti-cancer immune effect (abscopal
      effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral
      melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that
      hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia
      (2 X 43 degrees C / 45 minutes) and/or an immunogenic virus-like nanoparticle
      (VLP, 2 x 200 MUg) are capable of delivering a highly effective cancer treatment
      that includes an immunogenic component. Two tumors received all three therapeutic
      modalities, one tumor received radiation and hyperthermia, two tumors received
      radiation and VLP, and three tumors received only mNP hyperthermia. The treatment
      regimen is conducted over a 14-day period. All patients tolerated the treatments
      without complication and have had local and distant tumor responses that
      significantly exceed responses observed following conventional therapy (surgery
      and/or radiation). The results suggest that both hypofractionated radiation and
      hyperthermia have effective immune responses that are enhanced by the
      intratumoral VLP treatment. Molecular data from these tumors suggest Heat Shock
      Protein (HSP) 70/90, calreticulin and CD47 are targets that can be exploited to
      enhance the local and systemic (abscopal effect) immune potential of radiation
      and hyperthermia cancer treatment.

PMID- 29203955
TI  - Stabilizers of edaravone aqueous solution and their action mechanisms. 1. Sodium
      bisulfite.
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used as a free radical
      scavenging drug for the treatment of acute ischemic stroke in Japan since 2001.
      Edaravone is given to patients intravenously; therefore, it is distributed in the
      form of an aqueous solution. However, aqueous solutions of edaravone are very
      unstable because it is present as edaravone anion, which is capable of
      transferring an electron to free radicals including oxygen, and becomes edaravone
      radical. We observed the formation of hydrogen peroxide and edaravone trimer when
      aqueous edaravone solution was kept at 60 degrees C for 4 weeks. We proposed the
      mechanism of edaravone trimer formation from edaravone radicals. Lowering the pH
      and deoxygenation can effectively increase the stability of aqueous edaravone
      solution, since the former reduces edaravone anion concentration and the latter
      inhibits edaravone radical formation. Addition of sodium bisulfite partially
      stabilized aqueous edaravone solutions and partially inhibited the formation of
      edaravone trimer. Formation of bisulfite adduct was suggested by 13C NMR and HPLC
      studies. Therefore, the stabilizing effect of sodium bisulfite is ascribed to the
      formation of a bisulfite adduct of edaravone and, consequently, reduction in the
      concentration of edaravone anion.

PMID- 29203953
TI  - Are Heart Failure and Coronary Artery Bypass Surgery Patients Meeting Physical
      Activity Guidelines?
AB  - Purpose: The purpose of this study was to describe subjective and objective
      physical activity (PA) levels of two groups of cardiovascular patients who were
      either post-coronary artery bypass graft (CABG) surgery or diagnosed with heart
      failure (HF). Design: A descriptive comparative design was used for this
      secondary analysis of data from two prior studies. Methods: A convenience sample
      of 62 outpatients was used to examine PA objectively (Actiheart accelerometer)
      and subjectively (PA interview). Findings: Objectively, 33% of CABG patients and
      no HF patients met PA recommendations of >= 150 min/week. Subjectively, 56% of
      CABG and 38% of HF patients reported meeting PA recommendations. Conclusions: Few
      patients in the current study met PA recommendations. Clinical Relevance:
      Innovative rehabilitation nursing practice strategies are needed (e.g., use of
      activity trackers, making PA a vital sign) to assist patients in gaining the
      knowledge and skills to be more active and adhere to PA recommendations.

PMID- 29203954
TI  - Estimating bounds on causal effects in high-dimensional and possibly confounded
      systems.
AB  - We present an algorithm for estimating bounds on causal effects from
      observational data which combines graphical model search with simple linear
      regression. We assume that the underlying system can be represented by a linear
      structural equation model with no feedback, and we allow for the possibility of
      latent confounders. Under assumptions standard in the causal search literature,
      we use conditional independence constraints to search for an equivalence class of
      ancestral graphs. Then, for each model in the equivalence class, we perform the
      appropriate regression (using causal structure information to determine which
      covariates to adjust for) to estimate a set of possible causal effects. Our
      approach is based on the IDA procedure of Maathuis et al. (2009), which assumes
      that all relevant variables have been measured (i.e., no latent confounders). We
      generalize their work by relaxing this assumption, which is often violated in
      applied contexts. We validate the performance of our algorithm in simulation
      experiments.

PMID- 29203956
TI  - Stabilizers of edaravone aqueous solution and their action mechanisms. 2.
      Glutathione.
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has garnered attention since its
      approval for amyotrophic lateral sclerosis in Japan (2015) and the United States
      (2017). Edaravone is administered intravenously, and as such, is distributed in
      the form of an aqueous solution. However, aqueous solutions of edaravone are very
      unstable because they present as edaravone anions, which become edaravone
      radicals when the anion donates an electron to free radicals including oxygen. In
      this study, glutathione (GSH) stabilized an aqueous edaravone solution during
      storage at 60 degrees C for 4 weeks, and prevented the formation of potentially
      carcinogenic phenylhydrazine, while cysteine did not. One possible explanation is
      that GSH undergoes intermolecular hydrogen bonding with edaravone anions, while
      cysteine does not, as it favors intramolecular hydrogen boding. The combination
      of GSH and sodium bisulfite (NaHSO3) stabilized aqueous edaravone at room
      temperature for more than 1 year even under aerobic conditions. However, the U.S.
      Food and Drug Administration cautioned that NaHSO3 may cause allergic reactions.
      Therefore, we developed a stable edaravone aqueous solution without using NaHSO3,
      namely a combination of GSH with deoxygenation, which resulted in better
      stabilization of aqueous edaravone than the combination of GSH and NaHSO3.

PMID- 29203957
TI  - Parabanic acid is the singlet oxygen specific oxidation product of uric acid.
AB  - Uric acid quenches singlet oxygen physically or reacts with it, but the oxidation
      product has not been previously characterized. The present study determined that
      the product is parabanic acid, which was confirmed by LC/TOFMS analysis.
      Parabanic acid was stable at acidic pH (<5.0), but hydrolyzed to oxaluric acid at
      neutral or alkaline pH. The total yields of parabanic acid and oxaluric acid
      based on consumed uric acid were ~100% in clean singlet oxygen production systems
      such as UVA irradiation of Rose Bengal and thermal decomposition of 3-(1,4
      dihydro-1,4-epidioxy-4-methyl-1-naphthyl)propionic acid. However, the ratio of
      the amount of uric acid consumed to the total amount of singlet oxygen generated
      was less than 1/180, indicating that most of the singlet oxygen was physically
      quenched. The total yields of parabanic acid and oxaluric acid were high in the
      uric acid oxidation systems with hydrogen peroxide plus hypochlorite or
      peroxynitrite. They became less than a few percent in peroxyl radical-,
      hypochlorite- or peroxynitrite-induced oxidation of uric acid. These results
      suggest that parabanic acid could be an in vivo probe of singlet oxygen formation
      because of the wide distribution of uric acid in human tissues and extracellular
      spaces. In fact, sunlight exposure significantly increased human skin levels of
      parabanic acid.

PMID- 29203958
TI  - Role of catalytic iron and oxidative stress in nitrofen-induced congenital
      diaphragmatic hernia and its amelioration by Saireito (TJ-114).
AB  - Congenital diaphragmatic hernia (CDH) is a life-threatening neonatal disease that
      leads to lung hypoplasia and pulmonary hypertension. We recently found that
      maternal prenatal administration of Saireito (TJ-114) ameliorates fetal CDH in a
      nitrofen-induced rat model. Here, we studied the role of iron and oxidative
      stress in neonates of this model and in lung fibroblasts IMR90-SV in association
      with nitrofen and Saireito. We observed increased immunostaining of 8-hydroxy-2'
      deoxyguanosine in the lungs of neonates with CDH, which was ameliorated by
      maternal Saireito intake. Pulmonary transferrin receptor expression was
      significantly decreased in both CDH and CDH after Saireito in comparison to
      normal controls, indicating functional lung immaturity, whereas catalytic Fe(II)
      and pulmonary DMT1/ferroportin expression remained constant among the three
      groups. Saireito revealed a dose-dependent scavenging capacity with electron spin
      resonance spin trapping in vitro against hydroxyl radicals but not against
      superoxide. Finally, nitrofen revealed dose-dependent cytotoxicity to IMR90-SV
      cells, accompanied by an increase in oxidative stress, as seen by 5(6)
      chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and catalytic Fe(II).
      Saireito ameliorated all of these in IMR90-SV cells. In conclusion, catalytic
      Fe(II)-dependent oxidative stress by nitrofen may be the pathogenic cause of CDH,
      and the antioxidative activity of Saireito is at least partially responsible for
      improving nitrofen-induced CDH.

PMID- 29203959
TI  - Cancer cell-specific mitochondrial reactive oxygen species promote non-heme iron
      uptake and enhance the proliferation of gastric epithelial cancer cell.
AB  - Iron is an essential nutrient for life and is involved in many important
      processes such as oxygen transport and DNA synthesis. However, excess amounts of
      iron can cause carcinogenesis by producing reactive oxygen species. Thus, the
      cellular transport of iron must be tightly regulated. In the human body, iron may
      be present as heme or non-heme iron. The mechanisms governing the cellular
      transport of these forms have not been clearly elucidated. We previously reported
      that the expression of an important heme transporter, heme carrier protein 1 was
      regulated by cancer-specific reactive oxygen species derived from mitochondria.
      In this study, we have asked if mitochondrial reactive oxygen species may also be
      related with non-heme iron transport. In order to address this question, we have
      investigated the relationship between mitochondrial reactive oxygen species and
      accumulation of cellular non-heme iron in a rat gastric normal, cancer and
      manganese superoxide dismutase-overexpressing cancer cell line, in which reactive
      oxygen species from mitochondria are specifically scavenged. We have also
      analyzed the expression of divalent metal transporter 1 and ferroprotin, involved
      in the incorporation and excretion of non-heme iron, respectively, as well as a
      hypoxia-related transcription factor HIF-1alpha, to elucidate the molecular
      mechanism of non-heme iron accumulation.

PMID- 29203960
TI  - Monascus purpureus induced apoptosis on gastric cancer cell by scavenging
      mitochondrial reactive oxygen species.
AB  - Monascus purpureus is a red dye derived from yeast rice and has been used as
      color additives for food in East Asia. Monascus purpureus consists of several
      bioactive components. Some of these components work as a radical scavenger, thus
      monascus purpureus would also eliminate reactive oxygen species. Cancer cells
      maintain the high level of reactive oxygen species than normal cell and are death
      by imbalance in pro-oxidant/antioxidant homeostasis. In this study, we
      investigated whether monascus purpureus induced cancer specific cell death by
      scavenging reactive oxygen species. Compared to normal cell, monascus purpureus
      had cancer specific cytotoxicity. Monascus purpureus and lovastatin, its
      component, scavenged free radicals caused by a xanthine/xanthine oxidase system,
      thus Monascus purpureus is likely to scavenge reactive oxygen species by a
      synergistic effect between lovastatin and other components. Monascus purpureus
      also decreased reactive oxygen species derived from mitochondria in cancer cells,
      and cellular apoptosis was induced via activation of caspase-9. Induction of
      apoptosis by reduction of reactive oxygen species generation decreased acid
      ceramidase, and this mechanism could be involved with increasing ceramide
      accumulation in cells.

PMID- 29203961
TI  - Oleuropein improves insulin resistance in skeletal muscle by promoting the
      translocation of GLUT4.
AB  - As the beneficial effects of the Mediterranean diet on human health are well
      established, the phenolic compounds in olive oil have been gaining interest.
      Oleuropein, a major phenolic compound in olives, is known to reduce the blood
      glucose levels in alloxan-induced diabetic rats and rabbits, however, its effect
      on type 2 diabetes caused by obesity is not clear. The purpose of this study is
      clarifying the effect of oleuropein on the glucose tolerance in skeletal muscle
      under the condition of lipotoxicity caused by type 2 diabetes. Oleuropein
      enhanced glucose uptake in C2C12 cells without insulin. Translocation of glucose
      transporter 4 (GLUT4) into the cell membrane was promoted by activation of
      adenosine monophosphate-activated protein kinase (AMPK) but not protein kinase B
      (Akt). Physiological concentration of oleuropein (10 uM) was sufficient to
      express beneficial effects on C2C12 cells. Oleuropein prevented palmitic acid
      induced myocellular insulin resistance. Furthermore, in gastrocnemius muscles of
      mice fed a high fat diet, oleuropein also induced the GLUT4 localization into
      cell membrane. These results suggest the possibility of oleuropein to be
      effective for type 2 diabetes by reducing insulin resistance in skeletal muscles.

PMID- 29203962
TI  - Sake lees hydrolysate protects against acetaminophen-induced hepatotoxicity via
      activation of the Nrf2 antioxidant pathway.
AB  - Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen
      causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we
      investigated the protective effects of sake lees hydrolysate against
      acetaminophen-induced hepatotoxicity in mice. Sake lees hydrolysate was
      administered orally to ICR mice for seven days. Six hours after acetaminophen
      treatment, the mice were sacrificed, and blood and liver samples were collected
      for analysis. Treatment with acetaminophen markedly increased the levels of serum
      alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and
      alkaline phosphatase. Pretreatment with sake lees hydrolysate significantly
      prevented the increases in the serum levels of these enzymes and inhibited
      acetaminophen-mediated glutathione depletion. In addition, histopathological
      evaluation of the livers also revealed that sake lees hydrolysate prevented
      acetaminophen-induced centrilobular necrosis. The expression of gamma
      glutamylcysteine synthetase (gamma-GCS), hemeoxygenase-1 (HO-1) and nuclear
      factor erythroid 2-related factor 2 (Nrf2) in the liver were decreased after
      acetaminophen treatment, whereas pretreatment with sake lees hydrolysate led to
      an increased expression of all three proteins. Furthermore, sake lees hydrolysate
      induced the expression of these proteins in HepG2. These results suggested that
      sake lees hydrolysate could induces HO-1 and gamma-GCS expression via activation
      of the Nrf2 antioxidant pathway, and protects against acetaminophen-induced
      hepatotoxicity in mice.

PMID- 29203963
TI  - Ingestion of green tea with lowered caffeine improves sleep quality of the
      elderly via suppression of stress.
AB  - Epidemiological and animal studies have demonstrated that ingestion of green tea
      enhances healthy life. However, caffeine in green tea can interfere with sleep.
      In this report, we examined the effect of green tea with lowered caffeine, low
      caffeine green tea, on stress and sleep of the elderly. The participants (n = 10,
      mean age 89.3 +/- 4.2 years) drank five cups/day of standard green tea for 1
      week. Subsequently, they drank five cups/day of low-caffeine green tea for 2
      weeks. Salivary alpha-amylase activity (sAA) was measured as a stress marker.
      Sleep stages were measured using a portable electroencephalography (n = 7, 6
      female and 1 male). The level of sAA in the morning (sAAm) was significantly
      lower when the participants drank low-caffeine green tea than standard green tea.
      While the levels of sAAm were different among individuals, lower sAAm correlated
      with a higher quality of sleep. In those participants whose sAAm was lowered by
      the ingestion of low-caffeine green tea, some sleep parameters improved. Daily
      ingestion of low-caffeine green tea may be a beneficial tool for improving the
      quality of sleep of the elderly via the suppression of stress, although further
      research is required to fortify this hypothesis.

PMID- 29203964
TI  - Prediction of functional profiles of gut microbiota from 16S rRNA metagenomic
      data provides a more robust evaluation of gut dysbiosis occurring in Japanese
      type 2 diabetic patients.
AB  - We assessed whether gut microbial functional profiles predicted from 16S rRNA
      metagenomics differed in Japanese type 2 diabetic patients. A total of 22
      Japanese subjects were recruited from our outpatient clinic in an observational
      study. Fecal samples were obtained from 12 control and 10 type 2 diabetic
      subjects. 16S rRNA metagenomic data were generated and functional profiles
      predicted using "Phylogenetic Investigation of Communities by Reconstruction of
      Unobserved States" software. We measured the parameters of glucose metabolism,
      gut bacterial taxonomy and functional profile, and examined the associations in a
      cross-sectional manner. Eleven of 288 "Kyoto Encyclopedia of Genes and Genomes"
      pathways were significantly enriched in diabetic patients compared with control
      subjects (p<0.05, q<0.1). The relative abundance of almost all pathways,
      including the Insulin signaling pathway and Glycolysis/Gluconeogenesis, showed
      strong, positive correlations with hemoglobin A1c (HbA1c) and fasting plasma
      glucose (FPG) levels. Bacterial taxonomic analysis showed that genus Blautia
      significantly differed between groups and had negative correlations with HbA1c
      and FPG levels. Our findings suggest a novel pathophysiological relationship
      between gut microbial communities and diabetes, further highlighting the
      significance and utility of combining prediction of functional profiles with
      ordinal bacterial taxonomic analysis (UMIN Clinical Trails Registry number:
      UMIN000026592).

PMID- 29203965
TI  - The preventive effect of the impaired liver function for antiemetic therapy
      against chemotherapy-induced nausea and vomiting in hepatocellular carcinoma
      patients.
AB  - Transarterial chemoembolization and hepatic arterial infusion chemotherapy are
      recommended for the treatment in patients with intermediate stage of
      hepatocellular carcinoma. Impaired liver function was sometime observed in
      patients with hepatocellular carcinoma after transarterial chemoembolization or
      hepatic arterial infusion chemotherapy. However, what kinds of factors deeply
      influence in impaired liver function are not clear. A retrospective study was
      performed to evaluate the risk factors of impaired liver function in cisplatin
      naive patients treated with these therapies using cisplatin. Prior to and 2
      months after these therapies, we analyzed the liver function by Child-Pugh score
      in these patients. For assessing the severity of chemotherapy-induced nausea and
      vomiting, we utilized the Common Terminology Criteria for Adverse Events ver.
      4.0. In hepatocellular carcinoma patients received these therapies using
      cisplatin, the cancer stage and treatment without neurokinin-1 (NK1) antagonist
      were found to be independent risk factors of the impaired liver function. The
      treatment with NK1 antagonist was effective in reducing chemotherapy-induced
      nausea and vomiting and patients treated with NK1 antagonist kept their liver
      functions after cisplatin-used these therapies. The treatment with NK1 antagonist
      was effective in chemotherapy-induced nausea and vomiting and prevented the
      impaired liver function associated with cisplatin-used these therapies in
      hepatocellular carcinoma patients.

PMID- 29203966
TI  - Microvascular endothelial function in Japanese early adolescents.
AB  - Endothelial dysfunction is the early predictive factor for the development of
      atherosclerosis and future cardiovascular diseases in adulthood. The prevalence
      of endothelial dysfunction in children and early adolescents is increasing
      worldwide. Peripheral arterial tonometry is a noninvasive technique for assessing
      peripheral microvascular function and is used as a validated marker of
      endothelial function. We assessed anthropometric parameters, blood pressure,
      arterial stiffness, and peripheral endothelial function in 157 Japanese early
      adolescents (75 boys and 82 girls). We measured peripheral endothelial function
      by using peripheral arterial tonometry to determine the reactive hyperemia index,
      and assessed the association of reactive hyperemia index with parameters of
      anthropometry and arterial stiffness. The mean reactive hyperemia index of all
      subjects was 1.85 +/- 0.6, and there was no difference of reactive hyperemia
      index according to sex. Reactive hyperemia index was significantly associated
      with systolic and diastolic blood pressures, and had no correlation with
      anthropometric parameters and arterial stiffness markers. The reactive hyperemia
      index values among Japanese early adolescents were similar to those reported in
      previous studies on children and early adolescents. This noninvasive technique
      may be useful for the assessment of microvascular endothelial function among
      children and early adolescents.

PMID- 29203967
TI  - Patients' Rights in Cross-border Healthcare (Directive 2011/24/EU) and How It
      Applies to Turkey as a Negotiating Candidate Country.
AB  - Cross-border healthcare and patient mobility across European Union Member States
      has been on the agenda of EU Commission for the last decade. Directive 2011/24/EU
      on the application of patients' rights in cross-border healthcare went into force
      in 2013. The Directive mainly addresses the responsibilities of Member States in
      cross-border healthcare, regulates reimbursement procedure, and coordinates
      European reference networks and health technology assessment in the EU. The
      Directive has direct and indirect implications on Turkish health system. In this
      article, first an overview of Directive 2011/24/EU is addressed with special
      attention to its relation to patient rights and other EU legislations. Then,
      Turkish citizens' position in the scope of EU legislation on patient rights is
      considered. Finally, the ethical implications of the Directive, conceptualisation
      of cross-border patient mobility, and Turkey's particular position among other
      candidate countries regarding cross-border healthcare is discussed.

PMID- 29203968
TI  - 'I should have thought that Wales was a wet part of the world': Drought, Rural
      Communities and Public Health, 1870-1914.
AB  - From 1884 onwards, Britain experienced a series of major droughts, which reached
      their peak in the 'Long Drought' (1890-1909). Despite being imagined as a wet
      part of the world, rural Wales was hard hit as many communities did not have
      access to reliable water supplies. As medical officers of health and newspapers
      talked about water famines, alarm focused on questions of purity and disease as
      drought was presented as a serious health risk. Using rural Wales as a case
      study, this essay explores vulnerabilities to water scarcity during periods of
      drought to examine the material and socio-political impact of water scarcity and
      the resulting public health problems faced in rural areas. In addressing how
      droughts in rural communities were physical and social phenomena that generated
      considerable alarm about infectious disease, this essay also reveals how periods
      of water scarcity were an important determinant in improvements to rural water
      provision.

PMID- 29203971
TI  - Incidence of spinal epidural lipomatosis in patients with spinal stenosis.
AB  - Inroduction: Spinal Epidural Lipomatosis (SEL) is believed to be a rare disorder.
      The incidence and prevalence of clinically symptomatic SEL in patients with
      spinal stenosis has never been reported in the literature. Our study aims to
      determine the prevalence, incidence, and associated risk factors of SEL in
      patients with the diagnosis of spinal stenosis. Methods: This is a retrospective
      study. We reviewed the charts of 831 patients with the diagnosis of spinal
      stenosis over a 30 month period. All patients had spinal MRIs. Grading of SEL was
      performed using the Borre method. Results: 52 patients (21 female and 31 male)
      had symptomatic moderate and severe SEL. We found a prevalence of 6.26% and an
      annual incidence of 2.5%. SEL was most commonly seen at L5-S1 level. 27% had
      received corticosteroids. All SEL patients were overweight and 79% were obese.
      Conclusions: SEL is not uncommon in patients with spinal stenosis. SEL should be
      considered as a possible diagnosis in those with symptoms of spinal stenosis
      especially in those with associated risk factors.

PMID- 29203972
TI  - Current Status and Future Directions in Colorectal Cancer.

PMID- 29203970
TI  - Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis
      Herpetiformis.
AB  - A family of eleven proteins comprises the Janus kinases (JAK) and signal
      transducers and activators of transcription (STAT) signaling pathway, which
      enables transduction of signal from cytokine receptor to the nucleus and
      activation of transcription of target genes. Irregular functioning of the cascade
      may contribute to pathogenesis of autoimmune diseases; however, there are no
      reports concerning autoimmune bullous diseases yet to be published. The aim of
      this study was to evaluate the expression of proteins constituting the JAK/STAT
      signaling pathway in skin lesions and perilesional area in dermatitis
      herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group.
      Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from
      10 healthy volunteers. The localization and expression of selected STAT and JAK
      proteins were examined by immunohistochemistry and immunoblotting. We found
      significantly higher expression of JAK/STAT proteins in skin lesions in patients
      with BP and DH, in comparison to perilesional skin and the control group, which
      may be related to proinflammatory cytokine network and induction of inflammatory
      infiltrate in tissues. Our findings suggest that differences in the JAK and STAT
      expression may be related to distinct cytokines activating them and mediating
      neutrophilic and/or eosinophilic infiltrate.

PMID- 29203969
TI  - Cardiovascular Disease in Ageing: An Overview on Thoracic Aortic Aneurysm as an
      Emerging Inflammatory Disease.
AB  - Medial degeneration associated with thoracic aortic aneurysm and acute aortic
      dissection was originally described by Erdheim as a noninflammatory lesion
      related to the loss of smooth muscle cells and elastic fibre fragmentation in the
      media. Recent evidences propose the strong role of a chronic immune/inflammatory
      process in aneurysm evocation and progression. The coexistence of inflammatory
      cells with markers of apoptotic vascular cell death in the media of ascending
      aorta with aneurysms and type A dissections raises the possibility that activated
      T cells and macrophages may contribute to the elimination of smooth muscle cells
      and degradation of the matrix. On the other hand, several inflammatory pathways
      (including TGF-beta, TLR-4 interferon-gamma, chemokines, and interferon-gamma)
      seem to be involved in the medial degeneration related to aged and dilated aorta.
      This is an overview on thoracic aortic aneurysm as an emerging inflammatory
      disease.

PMID- 29203973
TI  - Long-Term Functional and Oncological Outcomes Following Intersphincteric
      Resection for Low Rectal Cancers.
AB  - Surgery for low rectal cancer often involves a permanent stoma. Intersphincteric
      resection (ISR) with colo-anal anastomosis is a valuable sphincter sparing
      surgical procedure that avoids the need for permanent stoma in patients with low
      rectal cancer. The aim of this study was to analyze the long-term functional and
      oncological outcomes following ISR. This was a retrospective analysis of patients
      with low rectal cancer who underwent ISR with colo-anal anastomosis in our
      institution between 2007 and 2015. All patients had a diversion stoma. Bowel
      function outcomes were assessed prospectively using Wexner incontinence score,
      low anterior resection syndrome score (LARS), and the Cancer Institute Quality of
      Life (QoL) questionnaire. The histological reports were reviewed to assess the
      oncological adequacy of the surgery. Patterns of recurrence and survival were
      analyzed in this group of patients. Thirty-three patients who underwent an ISR
      were eligible for this study. Laparoscopic resection was performed in five
      patients. All the patients received neoadjuvant chemoradiation except the two who
      received short course radiation and one who did not receive any neoadjuvant
      treatment. The median distance from the anal verge to the distal edge of the
      tumor was 3 cm (range 1.5-5 cm). Distal resection margins and circumferential
      resection margins were negative in all the patients. The 30-day post-operative
      mortality rate was 3.03%. In 20 patients with a median follow-up of 48 months,
      the 3-year overall survival was 95%. One patient had recurrence in the para
      aortic nodes. No patient had a local recurrence. Bowel function was assessed in
      18 patients who had a minimum stoma free period of 1 year. After a median of 43
      months following stoma closure, the median Wexner score was 3.56 (range 0-19),
      median LARS score was 4.78 (range 0-33), and the mean Cancer Institute QoL score
      was 151.56 +/- 15.741. The QoL was average to very high with an overall
      acceptable quality of life. In this study, ISR was associated with acceptable
      long-term functional and oncological outcomes. It can be considered as a safe
      alternative to a permanent stoma in selected patients with low rectal cancer.

PMID- 29203974
TI  - Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a
      Perspective Study Amongst Hospital Attending Eastern Indian Populations.
AB  - Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting
      colorectal carcinoma (CRC) progression. It is also evident that microsatellite
      instability (MSI) which results in a hypermutable phenotype of genomic DNA is
      common in CRC. Owing to the scarcity of reports from India, our aim of this study
      was to understand the clinicopathological correlations of CEA status with surgery
      and chemotherapy, correlate the same with socio-demographic status of the
      patients, determine the MSI status amongst them and understand the prognostic
      implications of CEA and MSI as CRC progression marker amongst patients. The serum
      CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme
      assay was carried out following the manufacturer's instructions using auto
      analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried
      out by PCR-SSCP. From our study, most frequently detected colorectal cancer was
      in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed
      a significant association with higher TNM staging, tumour size, smoking habit and
      MSI status (p < 0.05) but not with sex and site of cancer (p > 0.05). After
      surgery and chemotherapy, CEA and WBCs were decreased significantly (p < 0.05),
      while liver enzymes did not change significantly (p > 0.05). Overall,
      microsatellite instability was observed in approximately 40% of the populations.
      From our study, it was also evident that for both, MSI and abnormal CEA level
      predicted poor prognosis for the patient (by using Kaplan-Meier survival
      analysis; p = 0.04). Thus, CEA and initial MSI status can be used as prognostic
      markers of CRC.

PMID- 29203975
TI  - A Prospective Study of Distal Microscopic Spread in Rectal Cancer After
      Neoadjuvant Chemoradiation in Pinned and Unpinned Specimen.
AB  - The most important margin in determining the prognosis of rectal cancer is
      circumferential resection margin (CRM). But, the type of surgery is determined by
      distal rectal margin (DRM), whether sphincter saving procedure is possible or
      patient needs an abdominoperineal resection. There are no standardized uniform
      guidelines for measurement of DRM. The purpose of this study is to assess the
      distal microscopic spread beyond gross margin after neoadjuvant concurrent
      chemoradiation (CCRT) in rectal cancers, the factors influencing the distal
      microscopic spread, the shrinkage of the distal margin in pinned and unpinned
      fresh and fixed specimen, and to find out the best method of measurement of
      distal rectal margin. A prospective analytical study was conducted from May 2013
      through February 2015 in 47 cases of carcinoma rectum (both AR and APR) who had
      received neoadjuvant CCRT. Fresh specimen was collected within 30 min of specimen
      retrieval and a longitudinal cut was made in the distal margin of all specimens.
      One side of the specimen was pinned onto a cork board and the other side was left
      unpinned. Measurements were made from the distal end of clinical gross tumor. DRM
      was determined in both pinned and unpinned sides in fresh and fixed specimen. Of
      the 47 patients, 2 patients (4.2%) had small focus of tumor beyond gross margins,
      1 at 6 mm and another at 3.5 mm on the unpinned side. The average margin for
      fresh and fixed pinned specimens was 3.67 and 3.47 cm, respectively, with
      percentage shrinkage of 5.4% for the pinned specimens. The average margin for
      fresh and fixed unpinned specimens was 3.32 and 2.84 cm, respectively, with
      percentage shrinkage of 14.4% for the unpinned specimens. Six patients (12.7%)
      had complete pathological response. Correlation of distal margin was better in
      pinned specimen. A correction factor of 15% for shrinkage needs to be taken into
      account while assessing unpinned specimen. Only in 4.2% of patients, there was
      distal submucosal spread beyond gross margin. Long-term follow up is required for
      assessing adequacy of DRM post neoadjuvant CCRT.

PMID- 29203976
TI  - Laparoscopic Versus Open Approach for Intersphincteric Resection-Results from a
      Tertiary Cancer Center in India.
AB  - The study aims to compare open intersphincteric resection (OISR) with
      laparoscopic intersphincteric resection (LISR) in terms of short-term oncological
      and clinical outcomes. This is a retrospective review of a prospectively
      maintained database including all the patients of rectal cancer who underwent
      intersphincteric resection (ISR) at Tata Memorial Centre between 1st July 2013
      and 30th November 2015. Short-term oncological parameters evaluated included
      circumferential resection margin involvement (CRM), distal resection margin
      involvement, and number of nodes harvested. Perioperative outcomes included blood
      loss, length of hospital stay and 30-day postoperative morbidity and mortality.
      Chi-square test was used to compare the results between the two groups. Thirty
      nine cases of OISR and 34 cases of LISR were included in the study. Median BMI
      was higher in LISR group; otherwise, the two groups were comparable in all
      aspects. There were no conversions in LISR group. CRM involvement was seen in
      four patients (10%) in the conventional group compared to none in the LISR group.
      Median hospital stay was comparable between the two groups. Laparoscopic ISR is
      safe and can be performed with low conversion rate in selected group of patients.

PMID- 29203977
TI  - Radical Treatment of Rectal Cancer in Elderly Is Feasible than Feared: Results
      from a Tertiary Care Centre.
AB  - The thought of subjecting an elderly patient with rectal cancer to protocol-based
      neoadjuvant chemoradiation (NACTRT), surgery and adjuvant chemotherapy is sought
      with fear due to their multiple comorbidities and impaired functional status
      associated with the process of ageing. Hence, many a times the treatment is
      compromised and it is a fact that this subgroup of patients is underrepresented
      in most of the clinical trials. This study was aimed at analysing the
      perioperative and oncologic outcomes after protocol-based treatment of rectal
      cancer in the elderly patients, defined here as those with age >=70 years.
      Prospective analysis of medical records of rectal cancer patients was done who
      were >=70 years of age and were diagnosed and treated at Regional Cancer Centre
      (RCC), Thiruvanathapuram from 2008 to 2012. In this 5-year period, a total of 339
      rectal cancer patients underwent surgery as part of multimodality treatment with
      curative intent. Of them, 75 patients were >=70 years of age. Half of them had
      one or more comorbidities (54%) and majority were locally advanced at
      presentation (77%). Forty-seven (62%) cases received NACTRT and all of them
      tolerated RT dose (50.4 Gy) without modification. Anterior resection (AR) was
      performed in 48 (64%) and abdominoperineal resection (APR) in remaining.
      Diverting stoma was made in four; of which three remained permanent. Two
      colostomies were performed for delayed leaks. Three patients (4%) died within 30
      days due to leak, sepsis and cardiopulmonary causes. Two thirds (49/75) received
      adjuvant chemotherapy (ACT) but only 55% of them (27/49) could complete all the
      cycles without dose modification. The median survival was 28 months. The 3-year
      disease-free survival (DFS) and overall (OS) were 80.1 and 83.9%, respectively.
      There were 11 distant recurrences including two locoregional recurrences. The
      morbidity and mortality of multimodality therapy is reasonable to proceed with
      radical treatment with curative intent in the elderly patients with rectal
      cancer.

PMID- 29203978
TI  - Colorectal Cancer in India: An Audit from a Tertiary Center in a Low Prevalence
      Area.
AB  - Colorectal cancer (CRC) is a common cancer worldwide with a low reported
      incidence in India. There is significant geographical variation in the incidence
      rates, and the presentation may also vary. There are few studies evaluating the
      clinical profile of CRC in Indian patients. We analyzed a prospective database
      maintained at the Tata Memorial Hospital, a referral cancer center in Mumbai, of
      consecutive patients with CRC between August 2013 and August 2014. We captured
      details regarding the demography, symptoms, pathology, stage, and treatment plan.
      The aim was to assess the demographic and clinical details of patients with CRC
      in India and compare it with those of the reported literature. Eight hundred new
      patients with CRC were seen in the colorectal clinic in one year. The mean age
      was 47.2 years. Sixty-five percent were males. Patients were symptomatic for an
      average period of 4 months prior to presentation. The commonest symptoms were
      rectal bleeding (57%), pain (44%), and altered bowel habits (26%). Thirteen
      percent of the patients had signet ring tumors. The median CEA (carcinoembryonic
      antigen) level was 5.8 ng/mL. Most patients had localized or locally advanced
      disease. Twenty-eight percent of the patients had metastatic disease with liver
      being the commonest site of metastases (14%) followed by peritoneum and lung.
      More than half of the patients received treatment with a curative intent.
      Colorectal cancer in India differs from that described in the Western countries.
      We had more young patients, higher proportion of signet ring carcinomas, and more
      patients presenting with an advanced stage. Inadequate access to healthcare and
      socioeconomic factors may play a role in some of these differences.

PMID- 29203979
TI  - Young Vs Old Colorectal Cancer in Indian Subcontinent: a Tertiary Care Center
      Experience.
AB  - This study aims to compare patient, tumor, treatment-related factors and survival
      between young (<45 years) and old (>45 years) Indian colorectal cancer (CRC)
      patients. Total 778 patients of CRC were registered at tertiary cancer center in
      India between 1 August 2013 and 31 July 2014. Patients were followed up for
      median period of 27.73 months. Data regarding patient, tumor, treatment and
      survival-related factors were collected. Patients were divided in young (<=45
      years) and old (>45 years) age groups. Statistical analysis was done with SPSS
      software version 23. Young age group patients presented more commonly with poor
      histology, node-positive disease, and rectal site. Younger age group patients
      received multiple lines of neoadjuvant treatment. There was no significant
      overall survival difference in both groups of patients. On stratified stage-wise
      analysis, no significant overall survival (OS) difference was found between two
      groups (young vs old-1- and 3-year OS: 85.2 and 61.5% vs 81.5 and 64.5%,
      respectively; P = 0.881). On univariate analysis, gender, performance status,
      site, stage, differentiation, TRG, CRM status, signet ring type, and CEA level
      were significant prognostic factors. In disease-free survival (DFS) analysis, it
      is found that there is statistically significant difference in DFS (young vs old:
      1 and 3 years; 77.6 and 62.8% vs 85.8 and 74.1%, respectively; P value, 0.02),
      but when OS was analyzed for same group of patient, there was no statistical
      difference (P = 0.302). This study confirms the high incidence rates of CRC in
      young Indian patients. There is no OS difference between two age groups. In
      operated group of patients, there is higher DFS in older patients but no OS
      advantage at 3 years follow-up. Further long-term follow-up is required to see
      any OS difference.

PMID- 29203980
TI  - Quality of Life After "Total Mesorectal Excision (TME)" for Rectal Carcinoma: a
      Study from a Tertiary Care Hospital in Northern India.
AB  - Quality of life (QoL) is a key element in rectal cancer (RC) patients. There is
      not much data regarding this from North India. This study assesses QoL following
      low anterior resection (LAR) and abdominoperineal resection (APR), operated for
      low rectal tumors at a high-volume center in northern India. One-hundred-thirty
      patients of rectal carcinoma were prospectively assessed for quality of life
      using the European Organization for Cancer QLQ-30 and CR29 questionnaires and
      compared with reference data population. There was no significant difference in
      the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
      functional or symptom score between the study group and reference data
      population. Specific functional and symptom QoL scores of the study group were
      comparable to that of reference data population. There was no significant
      difference in the EORTC QLQ-C30 functional or symptom score between APR and LAR
      groups, except for the symptom of nausea and vomiting which was reported
      significantly more by the LAR group patients than APR group (p = 0.001). LAR
      patients had significantly higher scores with regard to nausea and vomiting than
      patients with an APR (p < 0.05). APR patients had significantly higher scores
      with regards to urinary frequency (p = 0.0001), abdominal pain (p = 0.0001), and
      embarrassment (p = 0.0001) than LAR patients. Quality of life after APR and LAR
      for rectal carcinoma was found to be comparable to the reference data population,
      and the QoL after APR was similar to that after LAR barring a few symptoms.

PMID- 29203981
TI  - Triple Test-a Predictor of Anastomotic Integrity in Patients Undergoing Low
      Anterior Resection After Neoadjuvant Chemoradiotherapy.
AB  - Anastomotic leak after low anterior resection for rectal cancer is a dreaded
      complication. Diversion stoma helps tiding over this crisis and it is routinely
      practised in most centres, especially in post chemoradiotherapy setting. But a
      diversion stoma has got its own problems. In this study, we attempt to use the
      triple test as a predictor of anastomotic integrity and thereby avoid a diverting
      stoma, and patients undergoing low anterior resection after neoadjuvant
      chemoradiotherapy were spared the trouble of a diverting stoma if the on table
      triple test was negative. Two hundred such consecutive patients were
      prospectively followed up in the postoperative period. The incidence of
      anastomotic leak and the factors predicting the same were analysed in this group
      of patients. The incidence of anastomotic leak in our study was 7%, which is much
      less when compared to published literature. The triple test was a reliable
      predictor of the integrity of anastomosis and if the test is negative, a
      diverting stoma can be avoided. Age more than 60 years and end-to-end anastomosis
      were found to be associated with increased incidence of leak, and patients with a
      negative triple test need not routinely undergo diversion stoma after a low
      anterior resection even in post chemoradiotherapy setting.

PMID- 29203982
TI  - Patterns and the Occurrence of KRAS Mutations in Metastatic Colorectal Cancers-a
      Study from Indian Regional Cancer Centre.
AB  - Mutation analysis of the KRAS oncogene is established as a predictive biomarker
      in Colorectal cancer (CRC). Many prospective clinical trials have shown that only
      CRCs with wild-type KRAS respond to anti-epidermal growth factor receptor (EGFR)
      treatment. Hence, mutation analysis is mandatory before treatment of metastatic
      CRCs. There are very few studies on the KRAS mutation status in the Indian
      setting. Hence, this study was done to document the patterns of KRAS mutations in
      CRCs reporting to a regional cancer centre in South India. Among 150 cases of
      metastatic colorectal cancer reporting over a period of 20 months, 48 random
      cases were analyzed for the KRAS mutational status of codons 12 and 13 of the
      KRAS gene by genomic sequencing. KRAS mutations in codons 12 and 13 were present
      in 9/48 (18.75%) of all analyzed CRCs. The common types of mutations were glycine
      to aspartate on codon 12 (p.G12D), glycine to valine on codon 12 (p.G12 V), and
      glycine to aspartate on codon 13 (p.G13D).

PMID- 29203983
TI  - Role of Hepatic Resection for HCC in the era of Transplantation; an Experience of
      Two Tertiary Egyptian Centers.
AB  - The surgical treatments of hepatocellular carcinoma (HCC) in a cirrhotic liver
      include both hepatic resection and liver transplant. While the liver transplant
      is considered as a golden therapy, it has some obstacles including shortage of
      organs especially living donors, economic circumstances, and the progression of a
      tumor while waiting for the transplant so the second choice which is resection
      should have a role. In this study, 84 patients with HCC (who were legible for
      transplant according to Milan and extended selection criteria) were enrolled for
      hepatic resection. The outcome including complication and the oncologic outcome
      was evaluated. We followed our patients for 15 months as a median follow-up
      (range from 3 to 50 months); we noticed 10 tumor relapse (11.7%) and seven lost
      (8.3%). We also noticed no recurrence. Patients' overall survival showed a median
      of 15 and 50 months, respectively. We can conclude that there is reasonability
      for HR as an effective optional treatment for patients with HCC who are legible
      for transplant particularly for patients with a Child-A scoring.

PMID- 29203984
TI  - Ovarian Metastases of Colorectal Origin: Treatment Patterns and Factors Affecting
      Outcomes.
AB  - The purpose of this study is to evaluate the patterns of treatment and factors
      affecting outcomes in ovarian metastases of colorectal origins treated at our
      institution and to assess the response of ovarian metastases to chemotherapy.
      Survival in R0 and R+ resections and patients receiving only chemotherapy is also
      analyzed. This is a retrospective study of 25 patients registered between January
      2012 and December 2015. Patient's age, disease status, mode of presentation,
      disease spread, mode of treatment, response to chemotherapy, completeness of
      resection, histology, and outcomes were considered as variables for analysis.
      There were 21 synchronous presentations and 4 metachronous presentations. In
      synchronous presentations, only 2 had extra-abdominal disease. Of these patients,
      15 underwent surgeries of various extents. The remaining 6 patients were treated
      with chemotherarpy initially. Only one of them could come up to surgery later. In
      R0 resections, disease recurred between 1 and 9 months (median 3.5 months). The
      recurrence was in peritoneum and ovaries. In operated cases, 12 of 15 patients
      received chemotherapy and 9 patients progressed on first line chemotherapy. In
      all 4 metachronous patients, the disease was in the peritoneum. No one underwent
      surgery for the recurrence due to the extensive nature of the disease. All
      received chemotherapy. Sixty-six percent ovarian metastases showed progression on
      chemotherapy. There was no significant difference in the median survival between
      patients treated with surgery plus chemotherapy (23 months) vs. those treated
      with chemotherapy alone (28 months). Age and presence of disease at other sites
      did not affect the outcomes. Non-signet ring cell histologies showed better
      outcomes compared to signet ring cell histology (p = 0.02). Synchronous
      presentation, R0 resections, and responsive disease showed better survival,
      however it was clinically not significant. Treatment of ovarian metastases of
      colorectal origins is varied but has consistently poor outcome. Non-signet
      histology was the only prognostic factor which showed better outcome. Survival
      was not different between patients treated with surgery+chemotherapy and
      chemotherapy alone but majority of ovarian metastases progressed on chemotherapy.
      Considering the poor response to chemotherapy and peritoneum being the most
      common site of disease, both in primary and recurrent setting, R0 resection
      should always be attempted after selecting the correct patients using PET scan,
      laparoscopy and standard exploratory protocols. Treatment should be tailored upon
      patient's status and disease burden with an aim to do complete cytoreduction
      whenever possible. CRS+HIPEC (cytoreductive surgery + hyperthermic
      intraperitoneal chemotherapy) can be considered on case to case basis as even R0
      resections tend to recur.

PMID- 29203985
TI  - Setting up of the Indian HIPEC Registry: A Registry for Indian Patients with
      Peritoneal Surface Malignancies.
AB  - There are various registries for patients with peritoneal metastases (PM) that
      aid pooling of data and generate evidence that dictates current clinical
      practice. This manuscript describes the setting up of the Indian HIPEC registry
      that was set up with a similar goal by a group of Indian surgeons. This is a
      registry for patients with PM treated with CRS and HIPEC in India. It also acts
      as a database for storing treatment-related information. Patients with PM from
      colorectal ovarian, gastric, appendiceal tumors, and other rare peritoneal
      tumors/metastases from rare tumors are enrolled in the registry. A coordinator
      updates the disease status of patients on a yearly basis. A private organization
      maintains the database. A non-disclosure agreement is signed between the company
      and each surgeon contributing to the registry to maintain confidentiality. For
      enrolling patients, securing institutional permission depends on the requirement
      of each institute; patient consent is mandatory. Data entry can be prospective or
      retrospective. To propose and conduct a study, the approval of a scientific
      committee linked to the registry is required. The Indian HIPEC registry is a
      practical database for Indian surgeons. There is no regulatory body that mandates
      collection and publication of scientific data in India. The onus is on each
      surgeon to capture valuable information pertaining to these common and rare
      diseases that could contribute to the existing scientific knowledge and guide the
      treatment of these patients in the future. The next challenge will be to enter
      data into the registry.

PMID- 29203986
TI  - CRS and HIPEC for PMP-Use of the LC-CUSUM to Determine the Number of Procedures
      Required to Attain a Minimal Level of Proficiency in Delivering the Combined
      Modality Treatment.
AB  - The learning curve for cytoreductive surgery (CRS) and hyperthermic
      intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) which peaks
      at 90 procedures for the surgeon may take several years to reach. The cumulative
      summation (CUSUM) test of the learning curve (LC-CUSUM) was used to assess the
      safety of the procedure (minimal level of proficiency for the surgeon) in terms
      of morbidity, mortality, and completeness of cytoreduction and early oncological
      failure before the peak of the learning curve had been reached. The limits for h0
      and h1 were set based on the results of large series of such cases published
      before. From 2011 to 2016, 77 patients with PMP underwent CRS and HIPEC. The mean
      peritoneal cancer index (PCI) was 28 and 75% of the patients had a CC-0/1
      resection. The grade 3-4 morbidity was 42.6% and the mortality was 5.2%. The 5
      year overall survival (OS) was 62.3% and the 3-year disease-free survival (DFS)
      was 71%. The LC-CUSUM analysis showed that for in-hospital mortality, acceptable
      limits are reached after the 57th case, after the 38th case for the grade 3-4
      morbidity and CC-2/3 resections both and after the 70th case for early
      oncological failure. The number of cases required to attain a minimal level of
      proficiency for each prognostic variable is different. Using the CUSUM test,
      surgeons can analyze their performance and determine the areas in which they need
      to improve before the peak of the learning curve is reached. These outcomes
      reflect the performance of the multidisciplinary team and not the surgeon alone.

PMID- 29203987
TI  - Ovarian Cancer in Young Women.
AB  - It is not clear how often epithelial tumours affect young women. This study aimed
      to evaluate the clinico-pathological pattern and survival outcome of women, 40
      years and younger, with cancer ovary. Women 40 years and younger, operated
      between 2008 and 2012 for ovarian cancer, were retrospectively recruited and
      followed up. The study design was descriptive as well as a survival analysis. A
      hybrid of retrospective and prospective cohort design was used for risk factor
      analysis. Of the 115 women less than 40 years being operated for probable ovarian
      cancer, 22 were excluded for various reasons. Demographic details, clinical
      presentations, histopathological features, treatments and survival outcomes were
      studied. The primary outcomes looked for were death and recurrence. Secondary
      outcomes were complications of treatment and fertility. The predominant histology
      in the study population was epithelial tumour (70%), and serous adenocarcinoma
      was the commonest tumour type. The overall survival rate was 87%, and progression
      free survival was 63%. Time to death and recurrence were dependent on stage of
      disease, histology of tumour, primary treatment and residual disease at surgery.
      In multivariate analysis, the hazard ratio for recurrence in advanced stages was
      12.6 (95% CI 3.5 to 45.5; p < 0.001) as compared to early stage disease.
      Epithelial ovarian cancers are common in young women. Death and recurrence are
      more likely in women with epithelial cancers, advanced stage disease and in those
      with residual tumour at cytoreductive surgery.

PMID- 29203988
TI  - Correlation of Transabdominal Ultrasonography and Cystoscopy in Follow-up of
      Patients with Non-muscle Invasive Bladder Cancer.
AB  - Cystoscopy (CS) is considered to be the gold standard in the follow-up of non
      muscle invasive bladder cancer. However, CS is invasive, time-consuming, and
      expensive. On the other hand, modern sensitive transducers have improved the
      imaging of urinary tract rendering transabdominal ultrasonography (US) more
      effective in visualizing intraluminal filling defects in the bladder than it was
      in the past. Twenty-five follow-up patients of low-risk bladder cancer meeting
      the inclusion and exclusion criteria were included in study. Ultrasonography of
      the bladder was performed by a single senior radiologist, and subsequently, these
      patients were subjected to flexible cystoscopy under local anesthesia. Pain score
      was calculated for each of the cystoscopies done. Findings of transabdominal
      ultrasound of the bladder were correlated and compared with those of cystoscopy.
      Subjects with US and/or CS findings suggestive of recurrence underwent
      transurethral resection of bladder tumor (TURBT) under general anesthesia and
      confirmation of the bladder carcinoma was achieved by the histopathological
      examination. Mean patient age was 60.56 years with range of 29 to 77 years. The
      sensitivity of modern ultrasonographic techniques was found to be 84.61% with
      specificity of 91.7% taking flexible cystoscopy as the gold standard for
      detection of recurrence. The accuracy of US was 88% with positive predictive
      value of 91.7% and negative predictive value of 84.61%. Technological evolution
      has improved the accuracy of ultrasonography in diagnosis of bladder carcinoma.
      It represents a valuable surveillance tool in selected sub group of low risk non
      muscle invasive bladder cancer patients.

PMID- 29203989
TI  - Strategies for Differentiating Gallbladder Carcinoma from Xanthogranulomatous
      Cholecystitis-a Tertiary Care Centre Experience.
AB  - Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic
      cholecystitis, characterized by focal or diffuse destructive inflammatory
      process. The importance of XGC is that it mimics gallbladder carcinoma (GBC) both
      preoperatively and intra-operatively, since it can present with pericholecystic
      infiltration, hepatic involvement and lymphadenopathy. As a result of this
      misdiagnosis which is not infrequent, the patient may need to undergo an
      unnecessary radical cholecystectomy rather than only a cholecystectomy which is
      associated with greater morbidity and mortality. Patients who underwent
      gallbladder and gallbladder-related operations during period of 5 years between
      2010 and 2014 were reviewed (n = 462). A comparison of clinical, biochemical,
      radiological and operative features were made between patients with carcinoma
      gallbladder (n = 101) and xanthogranulomatous cholecystitis (n = 22). Patient
      with a long history of recurrent abdominal pain with leucocytosis and who on
      imaging are found to have a diffusely thickened gallbladder wall (p < 0.01), with
      cholelithiasis, choledocholithiasis and sub-mucosal hypoattenuated nodules (p <
      0.05) are likely to have XGC while those with anorexia, weight loss, focal
      thickening of the gallbladder wall on imaging (p < 0.01) and dense local organ
      infiltration are more likely to have GBC. The presence of lymph nodes on imaging
      and the loss of fat plane interface between the liver and gallbladder are not
      differentiating factors. Differentiating XGC from GBC in preoperative setting is
      necessary to avoid radical procedures being done for a benign process. Certain
      clinical, radiological and intra-operative features aid in differentiating these
      benign and malignant process. However, the definitive diagnosis still remains a
      histopathological examination to avoid radical resection in patients who have a
      benign condition.

PMID- 29203990
TI  - Squamous Cell and Adenosquamous Carcinoma of Gall Bladder: a Clinicopathological
      Study of 8 Cases Isolated in 94 Cancers.
AB  - Adenosquamous/squamous cell carcinoma (AS/SCC) of the gall bladder is a rare
      histopathologic subtype that accounts for 1 to 12% of all the gall bladder
      carcinomas (GBC). Literature on these malignancies is limited. A retrospective
      analysis of 8 cases (study group) of pathologically proven AS/SCC of the
      gallbladder among 94 patients who underwent surgery for GBC from January 2001 to
      December 2014 was done. Twenty-four conventional gall bladder adenocarcinoma
      cases were selected as control group after matching for age and gender. Mean
      patient age was 57.8 years and six were females. Clinical presentation did not
      seem to be too different among the study and control group. Average tumor
      thickness was significantly higher in AS/SCC cases as compared to the control
      group (mean 3.1 versus 1.44 cm; p = 0.001). Immunohistochemistry for Ki-67 in
      adenosquamous carcinoma of the gall bladder showed much higher proliferative
      index in squamoid area than the adenocarcinoma areas (mean 31.3 versus 16.8%; p =
      0.0004). Study group showed 87.5% patients were in higher stage whereas only
      37.5% of the patients in control group presented at a higher stage. AS/SCC of the
      gall bladder presented at an advanced stage. Higher proliferation index in
      squamous component of adenosquamous carcinomas may account for higher T stage in
      these malignancies.

PMID- 29203991
TI  - Postoperative Delirium in Indian Patients Following Major Abdominal Surgery for
      Cancer: Risk Factors and Associations.
AB  - Postoperative delirium (POD) is not uncommon following major abdominal surgery
      with its incidence ranging between five and 51%. As cancer affects
      disproportionately, the population older than 65 years and as delirium is more
      common in the elderly, surgical oncology patients are at a higher risk of
      developing POD. The present study was undertaken to explore the impact and
      associations of POD in Indian patients undergoing oncological major abdominal
      surgery. A retrospective review of the electronic medical records in a tertiary
      cancer care institution of all postoperative patients who had undergone major
      gastrointestinal gynaecological and urological abdominal surgery for cancer and
      required psycho-oncology referral was performed. Patient, surgery and
      postoperative outcome-related data were collected. Statistical analysis was
      performed using univariate and multivariate logistic regression analysis. Out of
      824 patients who underwent major abdominal surgery, 33 patients (4.0%) were
      diagnosed with POD. In univariate analysis, older age and history of addiction
      were found to be statistically significantly associated with POD (p < 0.001).
      Among the postoperative factors, respiratory complications (p < 0.001), sepsis (p
      < 0.05), ICU stay > 24 h (p < 0.05) and electrolyte impairment (p < 0.05) were
      the significant associations with the POD. Thirty-day mortality was higher in the
      POD group (p < 0.05). In multivariate logistic regression analysis, advanced age,
      addictions, respiratory complications and sepsis were found to be significant
      associations with POD, p < 0.001. Postoperative delirium is associated with
      higher mortality. Older age, postoperative respiratory complications and sepsis
      are common contributory factors of postoperative delirium.

PMID- 29203992
TI  - Molecular Landscape and Treatment Options for Patients with Metastatic Colorectal
      Cancer.
AB  - Over the last 20 years, median survival for patients with metastatic colorectal
      cancer (CRC) has remarkably improved from about 12 to over 30 months, mainly
      because of the development of new agents and patient selection using predictive
      biomarkers. However, the identification of the most effective treatment for an
      individual patient is still a challenge. Molecular profiling of CRC has made
      great progress, but it is limited by tumor heterogeneity and absence of driver
      mutation. However, RAS, BRAF, and microsatellite instability are validated
      biomarker recommended by NCCN and ESMO. In this review, we discuss recent
      advances and future developments.

PMID- 29203993
TI  - Minimally Invasive Surgery for Rectal Cancer: Current Status and Future
      Perspectives.
AB  - Although laparoscopic resection for colon cancer has been proven safe and
      feasible when compared with open resection, currently no clear evidence is
      available regarding minimally invasive surgery for rectal cancer. This type of
      surgery may benefit patients by allowing fast recovery of normal dietary intake
      and bowel function, reduced postoperative pain, and shorter hospitalization.
      Therefore, minimally invasive surgeries such as laparoscopic or robot surgery
      have become the predominant treatment option for colon cancer. Specifically, the
      proportion of laparoscopic colorectal cancer surgery in Korea increased from 42.6
      to 64.7% until 2013. However, laparoscopic surgery for rectal cancer is more
      difficult and technically demanding. In addition, the procedure requires a
      prolonged learning curve to achieve equivalent outcomes relative to open surgery.
      It is very challenging to approach the deep and narrow pelvis using laparoscopic
      instruments. However, robotic surgery provides better vision with a high
      definition three-dimensional view, exceptional ergonomics, Endowrist technology,
      enhanced dexterity of movement, and a lack of physiologic tremor, facilitated by
      the use of an assistant in the narrow and deep pelvis. Recently, an increasing
      number of reports have compared the outcomes of laparoscopic and open surgery for
      colon cancer. Such reports have prompted a discussion of the outcomes of
      minimally invasive surgery, including robotic surgery, for rectal cancer. The aim
      of this review is to summarize current data regarding the clinical outcomes,
      including oncologic outcomes, of minimally invasive surgery for rectal cancer.

PMID- 29203994
TI  - An Overview of the Current Management of Bilobar Colorectal Liver Metastases.
AB  - Bilobar colorectal liver metastases (BCRLM) present a challenging scenario for
      liver surgeons globally. The following article aims to provide an overview of the
      different strategies which may be utilised in order to successfully manage
      advanced BCRLM.

PMID- 29203995
TI  - Management of Borderline Ovarian Tumors-Still a Gray Zone.
AB  - Borderline ovarian tumors (BOTs) are a heterogeneous group of non-invasive
      epithelial ovarian tumors that occur at a younger age, present in early stage,
      frequently associated with infertility but are easily curable. Although they may
      have symptomatic long-term recurrences, they have an excellent prognosis in spite
      of peritoneal spread. Among the epithelial tumors of the ovary, BOTs fall in the
      spectrum lying between cystadenomas (benign) and cystadenocarcinomas (malignant).
      Their oncological behavior is more aggressive than benign ovarian tumors but
      relatively less than that of malignant ovarian tumors. Since the age group
      affected is usually young females, preservation of fertility is an important
      aspect of treatment protocol. Although the management of these tumors has been
      extensively discussed, it still remains a controversial gray zone. In this
      review, epidemiology, pathogenesis, histologic subtypes, various surgical
      approaches, follow-up, and management of recurrence have been discussed. Choosing
      the best treatment still poses a challenge for the treating oncosurgeon.

PMID- 29203996
TI  - Metachronous Synchronous Sternal and Colonic Metastasis with Asymptomatic Colo
      colic Fistula from Carcinoma Ovary Rare Presentation of Ovarian Cancer.
AB  - Ovarian cancer is one of the most common gynecological cancers worldwide. It is
      the third leading cause of cancer among women in India. Metastatic disease to the
      visceral organs from ovarian cancer occurs as a terminal event in the natural
      history of the disease. In particular, spread to the bone and large bowel is
      infrequently described. The risk of distant metastasis increases in a recurrent
      setting. We describe a case of a 77-year-old lady, who was diagnosed for ovarian
      carcinoma in 2007 and underwent primary cytoreductive surgery, stage IIIc. She
      presented to us with asymptomatic rising cancer antigen (CA) 125 levels during
      follow-up. On evaluation she was found to have sternal and colonic deposits. She
      underwent left hemicolectomy and biopsy of sternal deposit. Histopathology
      revealed metastasis from the carcinoma ovary to the colon and sternum. This case
      report highlights the rare synchronous metastatic disease in a metachronous
      setting from ovarian carcinoma.

PMID- 29203997
TI  - Perianal Paget's Disease-a Case Report and a Review of Current Diagnosis and
      Management.
AB  - Paget's disease is an intraepithelial adenocarcinoma arising from the apocrine
      gland component of the skin. Paget's disease is most common in the breast but
      extra mammary disease is also seen. Perianal Paget's disease is a rare form of
      extramammary disease with few cases reported in literature. It can be primary
      arising from the skin or secondary-cutaneous metastases of anorectal or
      genitourinary malignancy. We hereby wish to report a case of perianal Paget's
      disease that presented as an eczematous lesion and was diagnosed incidentally on
      biopsy. After appropriate staging, the patient underwent wide local excision till
      negative margins were obtained. The resultant tissue defect was successfully
      covered by split-thickness skin grafting.

PMID- 29203998
TI  - Optimal Management of a Synchronous Diagnosis of Phaeochromocytoma and Colorectal
      Neoplasia.
AB  - The incidence rates of phaeochromocytoma and colorectal cancer (CRC) are
      approximately 1 and 65 per 100,000 per year, respectively. Simultaneous
      presentation of these conditions is rare and poses unique management challenges.
      We report on treatment strategies and clinical outcomes in a series of patients
      with colorectal neoplasia and phaeochromocytoma. Demographic and clinical details
      of four patients over a 4-year period were reviewed. The median (range) age at
      first presentation was 66 (52-70) years. Phaeochromocytoma (2.5-12.5 cm) was
      confirmed on biochemistry after incidental detection of an adrenal mass on CT
      scan-three had CT for staging of CRC and one had CT scan for weight loss.
      Adrenalectomy (three retroperitoneoscopic and one open procedure) was first
      performed after maximally tolerated alpha blockade; no significant complications
      were observed. Normalisation of biochemistry was confirmed and the patients then
      underwent colorectal surgery-laparoscopic right hemicolectomy, open right
      hemicolectomy (with further extensive surgery) for locally advanced cancer,
      laparoscopic low anterior resection and open high anterior resection. One
      respiratory infection and a seroma were the post-operative complications seen. In
      patients with a simultaneous diagnosis of phaeochromocytoma and CRC, surgical
      interventions should be staged. Adrenalectomy should first be performed to avoid
      haemodynamic instability during colorectal resection. A retroperitoneoscopic
      approach to the adrenal in patients with ipsilateral colonic tumours avoids
      transgressing the planes for colorectal resection. The synchronous diagnosis of
      these two rare conditions and the reported stimulatory effect of catecholamines
      on colorectal epithelia raise the possibility of an increased incidence of
      colorectal neoplasia in patients with phaeochromocytoma.

PMID- 29203999
TI  - Precocious Paratesticular Metastasis From Well-Differentiated Neuroendocrine
      Tumour of Ileocaecal Junction: A Case Report and Review.

PMID- 29204000
TI  - Malignant Gastrointestinal Neuroectodermal Tumor: a Unique Rare Neoplasm.
AB  - Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant
      tumor. It is also referred to as clear cell sarcoma-like gastrointestinal tumor
      (CCSLGT). It is an aggressive tumor with a high rate of local recurrence,
      metastases, and early death from disease. Its pathogenesis is not known. It shows
      evidence of neural differentiation and lacks immunohistochemical and
      ultrastructural evidence of melanocytic differentiation. It needs to be
      distinguished from various mimickers owing to its aggressive course. Herein, we
      report a case of GNET in a 55-year-old female patient.

PMID- 29204001
TI  - Primary Mucin Secreting Adenocarcinoma Bladder: a Case Series.
AB  - Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer.
      These tumours may have varied presenting complains with isolated mucusuria in
      some patients. As it is difficult to differentiate primary from secondary
      tumours, it is often a diagnostic dilemma. We narrate three cases of primary
      mucinous adenocarcinoma bladder and try to bring out the clinical and
      pathological features unique to this tumour along with the diagnostic importance
      of immunohistochemistry.

PMID- 29204002
TI  - Tailoring the Best Technique in the Surgical Management of IVC Thrombosis.

PMID- 29204003
TI  - Reoperation in Spinal Dysraphism.

PMID- 29204004
TI  - Neurocardiology and Atherosclerosis: The Effect of Ethnic Differences on Heart
      brain Interaction.

PMID- 29204005
TI  - Is Indocyanine Green Videoangiography a Good Substitute for Postoperative Digital
      Subtraction Angiography.

PMID- 29204006
TI  - Knowledge, Attitude, and Practice among Practitioners Regarding Epilepsy in
      Bhutan: A Rural and a Remote Country.
AB  - Purpose: Epilepsy is a major neurological disorder with many countries as
      scientifically silent and little-to-nothing known on various aspects of epilepsy.
      Methods: Taking background of a first multinational seminar on epilepsy in Bhutan
      and a short valid questionnaire pertaining to various aspects of epilepsy, before
      participation. Results: Large participation was achieved (76 out of 87
      approached, 87.3%; 53.0% males). Based on the responses of 76.0% lecturers and
      clinician and medical administration, 21.0% nurses, and 3.0% traditional
      practitioners, important derivations were obtained: positively, (a) event
      provided at least an opportunity to bring service providers at a common platform
      toward initiating particular epilepsy goals, (b) none regarded epilepsy as
      contagious or due to past sins, (c) all responded favorably to that "they found
      this event useful' and 'this event added something meaningful to them personally
      or professionally," (d) large participation indicated acceptance, need, and
      common interest among a number of stakeholders. Negatively, significant knowledge
      deficit was noted: for 38.4% electroencephalogram is essential for diagnosis,
      48.0% responded with incorrect definition of epilepsy, etc. Conclusions: Events,
      such as this, provides, for scientifically silent countries, basis for not only
      bringing service providers to a common platform but also to discuss to initiate
      particular epilepsy goals, to provide additional professional knowledge for
      strengthening service development, and to determine need and social acceptance
      around epilepsy. Important knowledge deficit was identified which cannot be fully
      explained through lack of time or limited training. There might be a need to
      reappraise the approach to teaching medical professionals about epilepsy.

PMID- 29204007
TI  - How Long does Denervation Take in Poliomyelitis? Or is it a Lifetime?"
AB  - Background and Objective: This study aims to determine the period of
      reinnervation in patients with poliomyelitis. This research was conducted to
      identify the appearance of denervation potentials in patients with poliomyelitis
      as indicators for reinnervation. Materials and Methods: A total of 246 male
      patients with poliomyelitis were assessed electrophysiologically between 1988 and
      2007. The mean age was 22.8 (18-42). It has been an average of 19.9 +/- 4.9 years
      since the beginning of complaints from the patients. Results: The patients had no
      complaints of newly developing muscle weakness, fatigue, muscle and joint pain,
      and difficulties in breathing and swallowing. Neurological examinations revealed
      the absence of myotomal pain and sensory loss. Upon assessment of the patients'
      limbs, the following findings were revealed: two patients had left upper and
      lower limb involvement, two patients had left upper and right lower limb
      involvement, 6 patients had left upper limb involvement, 12 patients had both
      lower limb involvement, 105 patients had left lower limb involvement, 1 patient
      had both upper limb involvement, 2 patients had right lower and upper limb
      involvement, 12 patients had right upper limb involvement, 6 patients had both
      lower limb involvement, 95 patients had right lower limb involvement, and 3 had
      all the three extremities affected. The needle electromyography revealed the
      presence of denervation potentials in 25.2% (62) of the patients. Conclusion:
      When poliovirus attacks the motor neuron, this neuron may be completely
      destroyed, damaged, or unaffected. Reinnervation occurs when nearby functioning
      motor units send out terminal axon sprouts to reinnervate the damaged muscle
      fibers. As a consequence of poliomyelitis, several muscle fibers become atrophic
      and fibrotic, but others continue to survive. This study showed that patients
      with a history of poliomyelitis experienced denervation with subsequent
      reinnervation for many years.

PMID- 29204008
TI  - A Clinical and Electrophysiological Study of Peripheral Neuropathies in
      Predialysis Chronic Kidney Disease Patients and Relation of Severity of
      Peripheral Neuropathy with Degree of Renal Failure.
AB  - Objective: To study the prevalence, clinical features, electrophysiological
      features, and severity of peripheral neuropathy in predialysis chronic kidney
      disease (CKD) patients with respect to severity of renal failure and presence of
      diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200
      predialysis CKD patients were assessed prospectively. Results: The prevalence of
      peripheral neuropathy in predialysis CKD patients in the present study was 45%
      based on clinical symptoms and 90% electrophysiologically. Mean age of 200
      predialysis CKD patients who participated in the study was 53.2 +/- 13.2 years.
      One hundred and thirty-six (68%) patients were male and 64 (32%) patients were
      female. Mean duration of disease was 2.2 +/- 1.6 years. Nearly 45% patients of
      patients had asymptomatic peripheral neuropathy in the present study, which was
      more common in mild-to-moderate renal failure group. One hundred twenty-six
      patients (63%) had definite damage and 54 patients (27%) had early damage. In
      mild-to-moderate renal failure (n = 100) and severe renal failure patients (n =
      100), 88% and 92% had significant peripheral neuropathy, respectively. Most
      common nerves involved were sural nerve, median sensory nerve, and ulnar sensory
      nerve. Diabetic patients (97%) showed more severe and high prevalence of
      peripheral neuropathy when compared to nondiabetic patients (83%). Most common
      patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor
      neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients,
      prevalence and severity of which increases as renal failure worsens. Predialysis
      patients with diabetes show higher prevalence and severity of peripheral
      neuropathy when compared with nondiabetics.

PMID- 29204010
TI  - Predictors of Dropout from Outpatient Mental Health Services; A Study from
      Rohtak, India.
AB  - Context: Dropout from mental health services is problematic in both developed and
      developing nations and often leads to poor outcomes. There is a lack of hospital
      based studies assessing the factors responsible for treatment dropout from mental
      health services in Indian settings. This study aims to contribute in that
      direction by presenting a study done in a tertiary care hospital in North India.
      Methodology: This was a hospital-based retrospective chart review carried out on
      randomly selected 139 patients at a tertiary hospital from January 1, 2014, to
      June 30, 2014. For this chart review, an abstraction form was designed that
      recorded six sociodemographic variables, nine clinical factors, and two outcome
      variables (more than one follow-up and active follow-up till 6 months). Results:
      Out of 139 patients, 53 patients dropped out after the first visit and 105
      patients dropped out by the end of 6 months. Lower education status (odds ratio
      [OR] = 8.2, 95% confidence interval [CI]: 2.30-29.50), severe mental illness (OR
      = 2.6, 95% CI: 1.05-6.49), and early referral to clinical psychologist (CP) (OR =
      7.8, 95% CI: 1.87-6.49) were predictors of better rates of follow-up after first
      visit. Lower education status (OR = 4.9, 95% CI: 1.45-17.08), early referral to
      CP (OR = 5.8, 95% CI: 2.09-38.35), and previous treatment history (OR = 8.9, 95%
      CI: 1.97-17.52) were predictors of better rates of follow-up at the end of 6
      months. Conclusion: The findings that education status, diagnosis, utilizing
      services of CP, and psychiatric services in past are correlated with dropout
      rates may be helpful in targeting patients who are more vulnerable to dropping
      out of care in the given setting.

PMID- 29204009
TI  - Outcome of Early versus Delayed Evacuation of Spontaneous Lobar Hematomas in
      Unconscious Adults.
AB  - Objective: To explore the difference in outcomes of medium-sized lobar hematomas
      evacuated in early versus delayed fashion among unconscious noncomatose
      individuals. Methods: A retrospective analysis of demographic, clinical, and
      radiological data of unconscious patients admitted with lobar hematomas during 18
      years was performed. Time to surgery was compared in various patient variables
      and characteristics. Outcome groups (favorable and poor) were also compared to
      find out any association with surgery timing, as well as potential indicators of
      outcome and mortality. Results: The mean follow-up period in this study was 7.5
      months after discharge. Two-thirds of the patients carried favorable prognosis at
      final follow-up with mortality (7.3%) included among poor cases. Time to surgery
      was not associated to any of the patient characteristics, except for
      international normalized ratio and associated chest problems which represented
      the main indicators of delayed surgery. Rebleeding after evacuation was
      associated with shorter time to surgery in clots <=35 cc but not in the whole
      group. Poor outcome was significantly associated with higher basal glucose
      levels, bigger hematomas, rebleeding after surgery, and delayed evacuation of
      clots >35 cc. The presence of mild intraventricular hemorrhage (IVH) per se was
      not associated with increased mortality or poor outcome; however, its volume was.
      Conclusion: Smaller lobar hematomas (<=35 cc) in unconscious adults (Glasgow Coma
      Scale 8-13) may be managed with initial conservative treatment, while larger
      hematomas (>35 cc) are better evacuated as early as possible. Basal glucose
      levels and volume of mild IVH should be considered in the future management
      planes.

PMID- 29204011
TI  - Effect of Scapular Stabilization Exercise during Standing on Upper Limb Function
      and Gait Ability of Stroke Patients.
AB  - Background: The purpose of this study was to determine the effect of scapular
      stabilization exercise during standing on a paretic side on upper limb function
      and gait ability of stroke patients. Methods: This study was a hospital-based,
      randomized controlled trial with a blinded assessor. A total of 17 patients with
      hemiplegic diagnosis after stroke were divided into two groups (9 patients in a
      study group and 8 patients in a control group). The study group received physical
      therapy and scapular stabilization exercise on a paretic side. Participants were
      subjected to initial evaluation before the treatment. Subjects were subsequently
      re-evaluated 4 and 8 weeks later to compare the changes. Measurements of hand
      function and gait ability were performed. Results: Based on multivariate analysis
      of variance for repeated-measures, there was a significant time effect for Timed
      Up and Go test (TUG) (F = 13.816, P = 0.000), Functional Gait Assessment (FGA) (F
      = 18.613, P = 0.000), and manual function test (MFT) (F = 16.777, P = 0.000). The
      group * time interaction effect was also significant for FGA (F = 4.966, P =
      0.024) and MFT (F = 6.946, P = 0.003), but not for TUG test (F = 3.343, P =
      0.069). Conclusion: Results of the present study indicated that scapular
      stabilization exercise during standing on a paretic side for 8 weeks had an
      effect on hand function and gait ability of hemiplegic patients after stroke.
      Further studies are needed to find the most proper exercise for stroke patients
      who have gait disability and upper limb dysfunction.

PMID- 29204012
TI  - Use of Preoperative Ependymal Enhancement on Magnetic Resonance Imaging Brain as
      a Marker of Grade of Glioma.
AB  - Objectives: Neural stem cells within the subventricular zone (SVZ) are thought to
      be responsible for the origin and the heterogeneous nature of the gliomas. The
      relationship of the gliomas to the SVZ can be appreciated as ependymal
      enhancement on contrast magnetic resonance imaging (MRI). This study evaluates
      the rate of ependymal enhancement and its association with the histopathological
      grade of gliomas. Patients and Methods: Seventy-five patients with radiological
      features of glioma were recruited. Preoperative MRI was evaluated for the
      presence of ependymal enhancement and fluid-attenuated inversion recovery (FLAIR)
      signal proximity of tumor to ependyma, and the association to grade was
      investigated. Results: Seventy-five patients studied showed a male predominance
      (62.66%) with a mean age of 44.91 +/- 13.64 years. Evidence of ependymal
      enhancement was positive in 24% (n = 18), 46.67% (n = 35) showed no evidence, and
      in 29.33% (n = 22), assessment was inconclusive. According to WHO grading, 76% (n
      = 57) were high-grade gliomas (HGGs) including Grade III (n = 17) and Grade IV (n
      = 40) and 24% (n = 18) were low-grade gliomas (LGGs) Grade II. HGGs were
      significantly associated with ependymal enhancement (P < 0.01) and FLAIR signal
      proximity to the ependyma (P < 0.001). Among HGGs, rate of ependymal enhancement
      and FLAIR signal proximity was more in Grade IV than Grade III but was not
      statistically significant (P > 0.05). Conclusion: SVZ is associated with HGGs.
      These MRI features can be helpful in predicting the tumor grade preoperatively
      and by including LGGs, the role of SVZ in the heterogeneous disease process of
      glioma can be studied as a whole, not only in the glioblastoma (GBM).

PMID- 29204013
TI  - A Family Study of Consanguinity in Children with Intellectual Disabilities in
      Barwani, India.
AB  - Background: Intellectual disability (ID) can be inherited in families through
      consanguineous marriage. The ID in an individual can be associated with the ID,
      epilepsy, and mental illness in their parents. Such connections can be seen more
      closely among consanguineous marriages in tribal and nontribal population in
      India. Objective: This study shows a few common patterns of the consanguineous
      relationship in the parents of children with ID in India. Materials and Methods:
      This is a case series research design. Extreme or deviant case sampling was
      applied. Data were collected in homes, camps, and clinical settings in the
      Barwani district of Madhya Pradesh, India. The patterns of consanguineous
      marriages and the relationship between children with ID and their relatives with
      ID, epilepsy, and mental illness were analyzed and reported with pedigree charts.
      Results: Multiple patterns of consanguineous marriages in tribal and nontribal
      populations were observed. ID was found to be associated in children with their
      relatives of the first, second, and third generations. Conclusion: ID may inherit
      in individuals from their relatives of the first, second, and third generations
      who have ID, epilepsy, or mental illness and married in the relationship.
      Appropriate knowledge, guidance, and counseling may be provided to potential
      couples before planning a consanguineous marriage.

PMID- 29204014
TI  - Mental Healthcare Delivery in Rural Greece: A 10-year Account of a Mobile Mental
      Health Unit.
AB  - Introduction: Patients living in rural and remote areas may have limited access
      to mental healthcare due to lack of facilities and socioeconomic reasons, and
      this is the case of rural areas in Eastern Europe countries. In Greece, community
      mental health service delivery in rural areas has been implemented through the
      development of the Mobile Mental Health Units (MMHUs). Methods: We present a 10
      year account of the operation of the MMHU of the prefectures of Ioannina and
      Thesprotia (MMHU I-T) and report on the impact of the service on mental health
      delivery in the catchment area. The MMHU I-T is a multidisciplinary community
      mental health team which delivers services in rural and mountainous areas of
      Northwest Greece. Results: The MMHU I-T has become an integral part of the local
      primary care system and is well known to the population of the catchment area. By
      the end of 2016, the majority of patients (60%) were self-referred or family
      referred, compared to 24% in the first 2 years. Currently, the number of active
      patients is 293 (mean age 63 years, 49.5% are older adults), and the mean
      caseload for each member of the team is 36.6. A significant proportion of
      patients (28%) receive care with regular domiciliary visits, and the provision of
      home-based care was correlated with the age of the patients. Within the first 2
      years of operation of the MMHU I-T hospitalizations of treatment, engaged
      patients were reduced significantly by 30.4%, whereas the treatment engagement
      rates of patients with psychotic disorders were 67.2% in 5 years. Conclusions:
      The MMHU I-T and other similar units in Greece are a successful paradigm of a low
      cost service which promotes mental health in rural, remote, and deprived areas.
      This model of care may be informative for clinical practice and health policy
      given the ongoing recession and health budget cuts. It suggests that rural mental
      healthcare may be effectively delivered by integrating generic community mental
      health mobile teams into the primary care system.

PMID- 29204015
TI  - Clinical Profile of Cognitive Decline in Patients with Parkinson's Disease,
      Progressive Supranuclear Palsy, and Multiple System Atrophy.
AB  - Background: There are very less data on the comparison between the cognitive
      profile in Parkinson's disease (PD) and Parkinson's-plus groups, especially in
      India. Aims: The aim of this study is to compare the cognitive profile across PD,
      progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) groups
      and compare them using Mini-Mental State Examination (MMSE), frontal assessment
      battery (FAB), and verbal fluency tests. Settings and Design: This was a cross
      sectional study. Materials and Methods: MMSE, FAB, and verbal fluency tests were
      administered in a total of 73 patients constituting 22 patients in MSA, 26
      patients in PD, and 25 patients in PSP group, respectively. Twenty-six
      participants both age- and gender-matched were enrolled in control group.
      Statistical Analysis: Statistical analysis was done using SPSS Version 20.0.
      Descriptive statistics were done to find out the mean and standard deviation of
      different variables. ANOVA was done for followed by post hoc Bonferroni test to
      assess the cognitive function in three groups. Results: ANOVA showed that there
      is a significant difference for MMSE scores (P = 0.038) being worse scores for
      PSP and maximum for MSA. A significant difference was found for FAB scores within
      three groups. There is a significant difference for FAB scores (P = 0.00003)
      being worse scores for PSP and highest scores obtained for PD. All the subtests
      of FAB test differed significantly except motor programming across MSA, PSP, and
      PD groups. Conclusions: Our data suggest that global cognitive impairment and
      executive dysfunction are worst in PSP among the three groups. Patients with MSA
      had significant cognitive decline as opposed to previous experience. FAB scores
      and verbal fluency tests are good tests to assess cognitive impairment in these
      diseases. Subsets of FAB score have significant differences but cannot help
      differentiating conclusively between these three diseases.

PMID- 29204016
TI  - Usefulness of Pulsed Arterial Spin Labeling Magnetic Resonance Imaging in New
      onset Seizure Patients and Its Comparison with Dynamic Susceptibility Contrast
      Magnetic Resonance Imaging.
AB  - Introduction: Dynamic susceptibility contrast (DSC) perfusion and pulsed arterial
      spin labeling (PASL) imaging are newer advanced magnetic resonance sequences
      which are capable of detecting vascular changes in patients with new-onset
      seizure disorder even when no significant abnormalities are visualized on
      conventional sequences. The purpose of our study is to establish utility of
      arterial spin labeling (ASL) in new-onset seizure patients and compare ASL with
      DSC perfusion sequence. Materials and Methods: Twenty-six patients coming to
      emergency department with new-onset seizure disorder were evaluated using DSC and
      ASL sequence. Perfusion asymmetry was assessed using region of interests taken at
      places where signal asymmetry was maximal. Results: PASL sequence showed focal
      vascular changes in form of hyperperfusion in four patients, hypoperfusion in
      nine patients, and normal perfusion in 13 patients. Altered perfusion whether
      hypo/hyperperfusion was detected in five out of 16 patients even when
      conventional sequences were normal. There was strong positive linear correlation
      between ASL and DSC with P = 0.001. Conclusion: Noninvasive PASL is capable of
      detecting vascular changes induced by seizure and is comparable to DSC sequence.
      Thus, it is recommended when there is a need for repeated evaluations; in follow
      up/therapy response assessment and when contrast administration is
      contraindicated.

PMID- 29204017
TI  - Clinical Evaluation and Diagnostic Utilities of Different Nerve Conduction Tests
      in 100 Patients with Carpal Tunnel Syndrome.
AB  - Background and Purpose: The purpose of the study is to determine whether the
      clinical profile of patients with carpal tunnel syndrome (CTS) has been same over
      the years with the help of routine and comparative electrodiagnostic tests.
      Methods: A prospective study of 100 patients with suspected CTS was conducted
      without controls. Three provocative maneuvers were performed. Routine and
      comparison nerve conduction tests were performed, i.e., second lumbrical
      interossei motor latency difference (2 LIMLD), digit 4 median-ulnar sensory
      latency difference (D4MUSLD), palm wrist distal sensory latency difference
      (PWDSLD), and digit 1 median-radial sensory latency difference (D1MRSLD). Data
      entry, analysis, and statistical evaluation were done using International
      Business Machines Corporation Statistical Package for the Social Sciences
      statistics package (IBM, SPSS). Results: A total of 195 hands of 100 patients met
      the criteria for CTS. Forty-three percentage of patients were homemakers.
      Considering the rapidly changing communication technology, we observed 84%
      patients had aggravation of symptoms with continuous long-term daily mobile phone
      use (>30 min per session per day). We noted positive Tinel's sign in only 25%.
      Phalen's sign was positive in 53 right hands with mean duration of 11.49s
      (standard deviation [SD] +/- 2.54 s) and was positive in 26 left hands with mean
      being 10.4 s (SD +/- 1.91 s). The mean motor distal latency of median was 4.67 ms
      (SD +/- 1.71 ms) and mean sensory distal latency of median was 3.24 ms (SD +/- 1
      ms). On internal comparison testing, mean difference in 2 LIMLD was 0.7 +/- 0.3
      ms, in D4MUSLD was 0.81 +/- 0.32, in PWDSLD was 0.71 +/- 0.20, and in D1MRSLD was
      0.76 +/- 0.32. Conclusion: Further analysis of clinical profile needs to be done,
      and new risk or provoking factors should be analyzed in patients with CTS.

PMID- 29204018
TI  - Role of Biomarkers in Differentiating New-onset Seizures from Psychogenic
      Nonepileptic Seizures.
AB  - Introduction: Review of literature revealed very limited studies considering a
      combination of serum prolactin (PRL) and serum creatine kinase (CK) as markers
      for differentiating epileptic and psychogenic nonepileptic seizures (PNES).
      Therefore, in the present study, we analyzed the role of serum PRL and serum CK,
      individually and in combination. Methodology: This prospective study was
      conducted in a tertiary care medical teaching hospital over a period of 18
      months. Patients aged over 15 years suspected to have new-onset seizures
      presenting within 5 h of ictus were included in this study. CK, serum PRL was
      measured at 0-1, 1-3, and 3-5 h after seizures. Results: Hundred subjects were
      studied for the role of serum PRL and serum CK in differentiating epileptic and
      PNES. The mean age was 42.24 years with a male:female ratio of 1.27:1. All
      patients of generalized tonic-clonic seizures (GTCS), who presented within 1 h,
      had elevated PRL, whereas 75% of patients with partial seizures had elevated PRL
      within 1 h of presentation. Nearly 91.66% of patients with GTCS who presented
      within 1 h had elevated CPK, whereas 70% of patients with partial seizures had
      elevated CPK. None of the patients diagnosed with PNES showed rise in either of
      the markers. Conclusion: In the present study, none of the patients with PNES
      showed raise in either serum PRL or CK. However, there was no correlation between
      the types of seizure and PRL or serum CK levels.

PMID- 29204019
TI  - Histologically Confirmed Intracranial Tumors Managed at Enugu, Nigeria.
AB  - Background: There is controversy about the global distribution of intracranial
      tumors (ICTs). The previous reports from Africa suggested low frequency and
      different pattern of distribution of brain tumors from what obtains in other
      continents. The limitations at that time, including paucity of diagnostic
      facilities and personnel, have improved. Objective: The objective of this study
      is to analyze the current trend and distribution of histology confirmed brain
      tumors managed in Enugu, in a decade. Methods: A retrospective analysis of ICTs
      managed between 2006 and 2015 at Memfys Hospital, Enugu. Only cases with
      conclusive histology report were analyzed. The World Health Organization ICT
      classification was used. Results: This study reviewed 252 patients out of 612
      neuroimaging diagnosed brain tumors. Mean age was 42.8 years and male-to-female
      ratio was 1.2:1.0. Annual frequency increased from 11 in 2006 to 55 in 2015.
      Metastatic brain tumors accounted for 5.6%, and infratentorial tumors represented
      16.3%. Frequency of the common primary tumors were meningioma (32.9%), glioma
      (23.8%), pituitary adenomas (13.5%), and craniopharyngioma (7.5%) (P = 0.001).
      Vestibular schwannoma accounted for 1.2%. Meningioma did not have gender
      difference (P = 0.714). Medulloblastoma, glioma, and craniopharyngioma were the
      most common pediatric tumors. About 8.7% presented unconscious (P < 0.001). There
      was no significant difference between radiology and histology diagnosis (P =
      0.932). Conclusion: Meningioma is the most frequent tumor with increasing male
      incidence, but the frequency of glioma is increasing. Metastasis, acoustic
      schwannoma, lymphoma, and germ cell tumors seem to be uncommon. Late presentation
      is the rule.

PMID- 29204020
TI  - Predictors of In-hospital Mortality of Acute Ischemic Stroke in Adult Population.
AB  - Introduction: Stroke is the second most common cause of mortality worldwide. Data
      regarding the predictors of mortality of acute ischemic stroke are widely
      discordant. Identifying the predictors and providing the utmost care to a high
      risk patient is still an unmet need in middle- to low-income countries. We did
      this study to identify the predictor of in-hospital mortality of acute ischemic
      stroke. Materials and Methods: We conducted a retrospective study of patients
      with acute ischemic stroke presented to the tertiary care center in eastern Nepal
      from January 2012 to December 2016. We enrolled patients of age 18 years and
      older with acute ischemic stroke in this study. The primary outcome of the study
      was in-hospital mortality of enrolled patients. Predictors of mortality were
      analyzed by comparing the patients with acute ischemic stroke who had mortality
      with those who survived. Results: The mean age of enrolled patients was 66 years.
      Among 257, the in-hospital mortality rate was 20.5%. The patients with in
      hospital mortality had lower Glasgow coma scale (GCS) score (9 vs. 12, P < 0.001)
      compared to those who survived. During admission, a patient with in-hospital
      mortality had significantly lower arterial oxygen saturation (92 vs. 95, P <
      0.001), higher pulse rate (91 vs. 83, P = 0.009), and higher respiratory rate (24
      vs. 21, P < 0.001) than those patients with acute ischemic stroke who survived.
      Conclusion: Lower GCS score, baseline higher pulse rate, higher respiratory rate,
      and lower arterial oxygen saturation are the predictors of in-hospital mortality
      of adult with acute ischemic stroke.

PMID- 29204021
TI  - Cranioplasty Using Autoclaved Autologous Skull Bone Flaps Preserved at Ambient
      Temperature.
AB  - Context: Decompressive craniectomy followed by cranioplasty (CP) uses autologous
      craniectomy flaps or synthetic materials like titanium. Sterilization and
      preservation methods for the autologous bone flaps continue to be the surgeon's
      choice. Aim: This study aimed to assess the short-term as well as long-term
      clinical outcomes of CP using autoclaved autologous bone grafts. Settings and
      Design: This retrospective observational study was performed on patients admitted
      in a tertiary care teaching neurosurgery department. Patients and Methods:
      Seventy-two patients who underwent CP with autoclaved autologous skull flaps
      preserved under ambient conditions with strict aseptic precautions were included
      in the study. Statistical Analysis Used: Frequencies and percentages of the
      various characteristics before and after the surgery were tabulated. Continuous
      variables were summarized as means and standard deviations. Results: The primary
      CP had a satisfactory clinical outcome in 62 cases (86.11%). Osteomyelitis was
      observed in four patients (5.56%) nearly 2 months after the surgery.
      Radiologically significant bone resorption was noted in a single patient (1.39%)
      after 1 year. Five patients (6.94%) developed bone fragmentation or fracture, and
      the mean time taken for this was about 36 months. In all these ten cases,
      secondary CP was successfully done using a prefabricated, patient-specific
      titanium mesh. Conclusions: The efficacy and safety of the studied craniectomy
      flaps used for cranial reconstruction showed a good patient outcome. Further
      retrospective studies with larger cohorts and prospective case-control studies
      are essential so as to issue standard guidelines for sterilization and
      preservation of autologous bone flaps.

PMID- 29204022
TI  - Impact of Road Traffic Injury to Pediatric Traumatic Brain Injury in Southern
      Thailand.
AB  - Background: Motor vehicle is a major transportation in Southern Thailand as the
      result of road traffic injury and death. Consequently, severe disability and
      mortality in pediatric traumatic brain injury (TBI) were observed from traffic
      accident, particularly motorcycle accident. To identify the risk of intracranial
      injury in children, the association of treatment outcome with various factors
      including mechanisms of injury, clinical characteristics, and intracranial
      pathology can be assessed. Materials and Methods: This was a retrospective study
      conducted on children, who were younger than 15 years old with TBI and were
      enrolled from 2004 to 2015. Several clinically relevant issues were reviewed and
      statistically analyzed. Results: A total of 948 casualties were enrolled.
      Compared with falling down, the motorcycle accident was significantly associated
      with intracranial injury (odds ratio 1.73, 95% confidence interval [CI] 1.08
      2.76). Other factors associated with intracranial injury were hemiparesis (odds
      ratio 5.69, 95% CI 1.44-22.36), positive of basal skull fracture signs (odds
      ratio 15.66, 95% CI 3.44-71.28), and fixed reaction to light of both pupils (odds
      ratio 5.74, 95% CI 1.71-19.23). Mortality found in thirty cases (3.2%).
      Furthermore, the risk of death correlated with motorcycle accident (P = 0.02) and
      severe head injury (P < 0.001). Neurosurgical intervention was not associated
      with outcome, but severe head injury, hemorrhagic shock, epidural, and subdural
      hematoma were impact factors. Conclusion: The findings demonstrate road traffic
      injury, especially motorcycle accident leading to brain injury and death.
      Prevention program is a necessary key to decrease mortality and disability in
      pediatric TBI.

PMID- 29204023
TI  - Trend of Neuropsychiatric Morbidity in Sub-Himalayan Region: An Audit of
      Retrospective Data Mining.
AB  - Background: There is a paradigm shift in health loss due to premature mortality
      and disability from neuropsychiatric disorders with major burden in low- and
      middle-income countries. Objective: To study the trend of admissions with
      neuropsychiatric and substance-use disorders in 3 years in psychiatry and
      medicine wards of tertiary care hospital in rural Himachal Pradesh. Methodology:
      A retrospective data mining was done from records of Inpatient wards of Dr. R. P.
      Government Medical College, Tanda, Himachal Pradesh, for the year 2013-2015.
      Demographic details and diagnosis of neuropsychiatric disorders, licit and
      illicit drug use, and their consequences in the form of hanging and poisoning
      were analyzed. Results: Majority of admissions were attributed to alcohol abuse
      which increased in 3 years significantly in the months of July-September (P =
      0.02) and October-December (P = 0.00). Almost all cases of neuropsychiatric
      disorders and majority of poisoning (58.2%) were observed among females. The
      productive young and middle age group (21-40 years) was mostly affected by all
      cause neuropsychiatric disorders (80.9%) and presented with poisoning (66.2%).
      Illicit drug abuse was on increasing drift among females. Conclusion: Indoor
      admissions were attributed to alcohol use and poisoning while neuropsychiatric
      disorders and substance abuse were probably dealt with at outpatient level.
      Treatment pertaining to mental illnesses was sought in severe cases only. Data
      demonstrating population burden are needed urgently to address the barriers to
      treatment to reduce burden.

PMID- 29204024
TI  - Behavioral Problems and Intelligence Quotient Changes in Pediatric Epilepsy: A
      Case-Control Study.
AB  - Background: Epilepsy is the most common chronic neurological disease and has
      neurological impairment as an important comorbidity. Objective: To find
      behavioral problems and intelligence quotient (IQ) changes associated with
      epilepsy and to know the association of variables such as frequency, type of
      seizures, and duration of disease with cognitive impairment. Materials and
      Methods: A descriptive cross sectional study, consisting of 50 cases (patients of
      epilepsy) and 50 controls (other patients of same socioeconomic status) was
      conducted at S.P. Medical College, Bikaner. The patients were subjected to
      detailed clinical history, thorough examination, Pediatric Symptom Checklist, and
      Bhatia's Battery of Performance intelligence Test. Data analysis was carried out
      with the help of SPSS 22 software. Results: The prevalence of behavioral problems
      in generalized and partial seizure group was high (42% and 53.8%) as compared to
      control group (9%). Low IQ was present more in the patients (44%) of generalized
      and partial seizure group as compared with the control group, and results were
      statistically significant. Furthermore, behavioral problems were more in patients
      who were having more number of seizures (>=3 per year) with significant P values
      (chi2 = 5.067, P = 0.024). Conclusion: We conclusively found that behavioral
      problems and cognitive factors, apart from control of seizures, must be kept in
      mind to determine how well a child with epilepsy progresses toward independence.

PMID- 29204025
TI  - Sacroiliac Pain: A Clinical Approach for the Neurosurgeon.
AB  - Pain originating from sacroiliac joint may also cause pain in the lumbar and
      gluteal region in 15% of the population. The clinical manifestation represents a
      public health problem due to the great implications on the quality of life and
      health-related costs. However, this is a diagnosis that is usually ignored in the
      general clinical practice; probably because of the unknown etiology, making
      harder to rule out the potential etiologies of this pathology, or maybe because
      the clinical criteria that support this pathology are unknown. By describing
      several diagnostic techniques, many authors have studied the prevalence of this
      pathology, finding more positive data than expected; coming to the conclusion
      that even though there is no diagnostic gold standard yet, an important amount of
      cases might be detected by properly applying several tests at the physical
      examination. Thus, it is necessary to have knowledge of the physiopathology and
      clinical presentation so that diagnosis can be made to those patients that
      manifest this problem. We present a clinical approach for the neurosurgeon.

PMID- 29204026
TI  - Commentary.

PMID- 29204027
TI  - A Simplified Overview of World Health Organization Classification Update of
      Central Nervous System Tumors 2016.
AB  - After 8 years, an update of central nervous system (CNS) tumors was published in
      2016 after 2007. First time ever, molecular markers along with histology have
      been used in classification of any tumor. Major changes are seen in glioma and
      medulloblastoma groups. Few entities have been added such as diffuse midline
      glioma, H3 K27M-mutant, RELA fusion-positive ependymoma, embryonal tumor with
      multilayered rosettes, C19MC-altered, and hybrid nerve sheath tumors. Few
      variants and patterns that no longer have diagnostic and/or biological relevance
      and have been deleted such as glioblastoma cerebri, protoplasmic and fibrillary
      astrocytoma, and cellular ependymoma. Other changes include deletion of term
      "primitive neuroectodermal tumor," addition of criterion of brain invasion in
      atypical meningioma, separation of melanotic schwannoma from other schwannoma,
      and combination of solitary fibrous tumors and hemangiopericytoma as one entity.
      There is also expansion of entities in nerve sheath tumors and
      hematopoietic/lymphoid tumors of the CNS. In this review article, we tried to
      review CNS tumors 2016 classification update in a simplified manner; comparing
      the differences between 2016 and 2007 CNS tumors classifications with brief
      description of important molecular markers and finally utility as well as
      challenges of this classification.

PMID- 29204028
TI  - Spontaneous Spinal Discitis and Spondylodiscitis: Clinicotherapeutic Remarks.

PMID- 29204029
TI  - Sir Hugh Cairns: The Neurosurgeon Who Introduced Crash Helmets.
AB  - Statistics prove that more Indians die in Road traffic related accidents than in
      wars. Prior to World War II, the death toll across the world used to be very
      high. It was at this juncture that a Military Neurosurgeon named Hugh Cairns
      introduced the compulsory wearing of crash helmets and brought about a reduction
      in mortality by more than 50%. Within a decade of introduction of crash helmets
      in Britain, the entire world followed suit. The results of his efforts are here
      for all of us to see. This innovative military neurosurgeon is credited as the
      one who introduced the concept of mobile neurosurgical units during world war and
      also the first proponent of usage of penicillin in war. His concepts in war
      surgery are still followed by militaries across the world. This article comes as
      a tribute to this great Neurosurgeon who helped in saving millions of lives.

PMID- 29204030
TI  - Symptoms of Neurotoxicity among Carpenters Living in Rural Ecuador: A Population
      based Study (The Atahualpa Project).
AB  - Background: There is no information on the prevalence of symptoms related to
      neurotoxicity among carpenters working in underserved populations. To assess the
      magnitude of the problem, we conducted a population-based study in Atahualpa, a
      rural Ecuadorian village, where most men work as carpenters under poor safety
      conditions. Methods: All men aged 40-75 years living in Atahualpa were identified
      during a door-to-door survey and evaluated with a general demographic
      questionnaire, the Q16 questionnaire, the depression axis of the Depression
      Anxiety Stress Scale-21, and the Montreal Cognitive Assessment (MoCA). Results:
      Among 230 participants, 63% were carpenters. Seventy participants (30%) had a
      positive Q16 questionnaire (>=6 points), which suggested neurotoxicity. In a
      logistic regression model adjusted for age, education, alcohol intake, symptoms
      of depression, and MoCA score, the proportion of Q16 positive persons was 39.1%
      for carpenters and 15.9% for noncarpenters (odds ratio: 3.53, 95% confidence
      interval: 1.75-7.15, P < 0.0001). In a generalized linear model, adjusted mean
      scores in the Q16 questionnaire were 4.9 for carpenters and 3.6 for noncarpenters
      (beta: 1.285, standard error: 0.347, P < 0.0001). There was no correlation
      between scores in the Q16 questionnaire and the MoCA (Pearson correlation
      coefficient = -0.02), and the only significant covariate in the multivariate
      linear model was age, with every 10 years of age difference contributing 0.64
      points in the Q16 questionnaire. Conclusion: This study shows a high prevalence
      of symptoms associated with neurotoxicity among carpenters after adjusting for a
      number of confounders. Long-term exposure to toxic solvents is the most likely
      explanation to this finding.

PMID- 29204031
TI  - Intracranial Ossified Metaplastic Meningioma: Unusual Cause of Headache.

PMID- 29204032
TI  - Subarachnoid Hemorrhage Due to Ruptured Intracranial Aneurysm Arising from a
      Vertebral Artery-Bihemispheric Posterior Inferior Cerebellar Artery Bifurcation.
AB  - Although the anatomy of the posterior inferior cerebellar artery (PICA) is highly
      variable, a solitary PICA supplying both hemispheres of the cerebellum is rare. A
      76-year-old woman presented with severe headache and subsequent loss of
      consciousness and was admitted to our hospital. Initial computed tomography
      showed subarachnoid hemorrhage. Three-dimensional digital subtraction angiography
      revealed a saccular aneurysm arising from the right vertebral artery (VA)-PICA
      bifurcation. The PICA branching from the right VA was enlarged, tortuous, and
      crossed the midline to supply both cerebellar hemispheres. This right PICA was
      interpreted as a bihemispheric PICA. Recognizing this variant preoperatively
      could help prevent complications of surgery. Careful follow-up studies are
      necessary in cases with bihemispheric PICA to monitor for the development of
      aneurysm at the junction between the bihemispheric PICA and the VA or the distal
      portion of the bihemispheric PICA.

PMID- 29204033
TI  - White Matter Changes in Corpus Callosum in a Patient with Idiopathic Normal
      Pressure Hydrocephalus.
AB  - Idiopathic normal pressure hydrocephalus (INPH) is characterized by the clinical
      triad of gait and cognitive dysfunction and urinary incontinence.
      Ventriculoperitoneal (VP) shunting is often required for treatment. Review of
      literature shows few case reports discussing benign magnetic resonance imaging
      (MRI) T2 hyperintense changes in the corpus callosum of NPH patients after
      shunting due to mechanical compression of the middle and posterior regions of the
      body against falx cerebri leading to ischemic demyelination. These changes can be
      a delayed phenomenon and may interfere with clinical evaluation and may lead to
      unnecessary procedures and investigations. We present a patient with NPH who was
      admitted to the neurocritical care unit in coma with quetiapine and trazodone
      overdose. Diffuse changes in the body of the corpus callosum were seen on MRI
      suspicious for acute vasogenic edema due to drug overdose. However, it was later
      determined to be due to the VP shunting for the NPH. We report this case to raise
      the awareness of neuroimaging changes in patients with NPH who have VP shunting.

PMID- 29204034
TI  - Chromosome 15 Duplication and Attention-Deficit Hyperactivity Disorder.
AB  - Chromosome 15 duplication has been associated with a number of psychiatric
      illnesses including psychosis and autism. However, literature on association with
      attention-deficit hyperactivity disorder (ADHD) is scant. This case report
      describes a patient with chromosome 15 duplication diagnosed with ADHD in our
      neurodevelopmental clinic. The possible biological underpinnings are discussed
      along with possible challenges in diagnosis and management. The need for better
      understanding ADHD as a behavioral phenotype in such cases along with need for
      tailored management strategies is emphasized.

PMID- 29204035
TI  - Commentary.

PMID- 29204036
TI  - Flow-diverting Stent-assisted Coil Embolization of a Ruptured Internal Carotid
      Artery Blister Aneurysm with the Pipeline Flex Embolization Device.
AB  - Internal carotid artery (ICA) blister aneurysms are rare and challenging to
      successfully treat, using contemporary surgical or endovascular approaches,
      without partial or complete compromise of the parent vessel. We describe the use
      of a resheathable flow diverter, the Pipeline Flex Embolization Device (PFED) to
      perform stent-assisted coiling of a ruptured supraclinoid ICA blister aneurysm in
      a 56-year-old female who presented with a high-grade subarachnoid hemorrhage
      (SAH). The first PFED was deployed across the aneurysm neck to jail a
      microcatheter within the aneurysm dome, and then, two small coils were delivered
      into the aneurysm. After removing the coiling microcatheter, the second PFED was
      telescoped into the first PFED. There were no postprocedural complications, and
      follow-up magnetic resonance angiography 15 months after embolization showed
      complete aneurysm obliteration. Flow-diverting stent-assisted coiling should be
      considered as a reconstructive, vessel-preserving, endovascular treatment option
      for appropriately selected patients with ruptured ICA blister aneurysms. However,
      future studies are necessary to assess the periprocedural safety in the setting
      of acute SAH.

PMID- 29204037
TI  - Staged Multimodality Treatment of a Large Ruptured Fusiform Supraclinoid Internal
      Carotid Artery Aneurysm: Microsurgical Clip-assisted Endovascular Coiling.
AB  - In the contemporary era of aneurysm management, large fusiform aneurysms
      presenting with subarachnoid hemorrhage (SAH) remain particularly challenging
      lesions to successfully manage. We describe a staged, multimodal treatment
      strategy for a 71-year-old patient who presented with a large ruptured fusiform
      aneurysm of the supraclinoid internal carotid artery (ICA) and a fetal posterior
      communicating artery which originated from the inferomedial aspect of the
      aneurysm. In the first stage, we performed a partial microsurgical clip
      reconstruction of the fusiform aneurysm and secured its rupture site, which was
      identified intraoperatively. This left two residual saccular components of the
      aneurysm, which were targeted with endovascular coiling in the same
      hospitalization after the patient had convalesced from the SAH and was beyond the
      vasospasm window. We believe that this combined approach of clip-assisted coiling
      can be employed instead of endovascular flow diversion or microsurgical bypass
      for appropriately selected patients with ruptured fusiform ICA aneurysms.

PMID- 29204038
TI  - Venous Sinus Stenting using Transcranial Access for the Treatment of Idiopathic
      Intracranial Hypertension in a Pediatric Patient.
AB  - A 4-year-old male with headaches, papilledema, intracranial hypertension, and
      bilateral transverse sinus (TS) stenosis underwent attempted percutaneous
      placement of a right TS stent. Stent deployment was not technically feasible due
      to the stiffness of the stent and tortuosity of the patient's jugular bulb.
      Therefore, the patient underwent hybrid endovascular stenting of the right TS
      using neuronavigation and direct access of the TS following a single burr hole
      craniectomy. Two Express 8 mm * 17 mm balloon-mounted stents were deployed into
      the right TS, which resulted in obliteration of the preexisting trans-stenosis
      pressure gradient and decreased intracranial parenchymal pressure as monitored
      through an intracranial pressure bolt. The patient's headaches and papilledema
      resolved, and follow-up imaging demonstrated no in-stent or stent-adjacent
      stenosis. This case demonstrates the feasibility of combining minimally invasive
      open surgical access to allow direct cannulation for venous sinus stenting.

PMID- 29204039
TI  - Commentary.

PMID- 29204040
TI  - Postepidural Spinal Intradural Arachnoid Cyst: A Rare Case Report.
AB  - Compression of the neural structures in spine by an intradural arachnoid cyst is
      a rare entity. At times such a cyst is an incidental finding. Spinal epidural
      injection is one of the few rare etiological factors for its development.
      Symptomatic cysts can present with variable neurological manifestations depending
      on the spinal level involved. This includes back pain, lower limb weakness, and
      sphincteric dysfunction. If asymptomatic, they can be followed radiologically.
      Surgical decompression along with a histological diagnosis is reserved for cysts
      that are enlarging, symptomatic or the ones for whom the diagnosis is uncertain.
      Incomplete excision of cyst wall or simple fenestration and decompression
      mandates close follow-up, clinically and radiologically for further recurrences.

PMID- 29204041
TI  - Delayed Visual Loss Following Transcranial Surgery for Tuberculum Sella
      Meningioma.
AB  - Postoperative visual loss is a dreaded complication following transcranial
      excision of tuberculum sella meningioma. Visual deterioration is commonly noticed
      immediately after surgery, and delayed deterioration after 72 h is uncommon. We
      report a case of delayed postoperative deterioration in a 48-year-old female and
      discuss the possible mechanisms.

PMID- 29204042
TI  - Papilledema: A Comprehensive Assessment.

PMID- 29204043
TI  - Simultaneous Convexity Meningioma and Prolactinoma.

PMID- 29204044
TI  - Intraventricular Bleed following Surgery for Giant Cystic Vestibular Schwannoma:
      A Rare Complication.

PMID- 29204045
TI  - Proprioceptive-Induced Reflex Postinfarct Seizures: A Rare Occurrence.

PMID- 29204046
TI  - International Neurosurgery Rotation in New Zealand: Analysis of Operative
      Experience.

PMID- 29204047
TI  - Friedreich Ataxia: Clinical Feature and Electrophysiological Symptoms.

PMID- 29204048
TI  - Hydrocephalus Caused by H3N2 Type A Influenza Virus or Cerebellopontine Angle
      Schwannoma?

PMID- 29204049
TI  - Commentary.

PMID- 29204050
TI  - Current and emerging pharmacological therapy for non-alcoholic fatty liver
      disease.
AB  - The main treatment of patients with non-alcoholic fatty liver disease (NAFLD) is
      life style modification including weight reduction and dietary regimen. Majority
      of patients are safely treated with this management and pharmacologic
      interventions are not recommended. However, a subgroup of NAFLD patients with non
      alcoholic steatohepatitis (NASH) who cannot achieve goals of life style
      modification may need pharmacological therapy. One major obstacle is measurement
      of histological outcome by liver biopsy which is an invasive method and is not
      recommended routinely in these patients. Several medications, mainly targeting
      baseline mechanism of NAFLD, have been investigated in clinical trials for
      treatment of NASH with promising results. At present, only pioglitazone acting as
      insulin sensitizing agent and vitamin E as an anti-oxidant have been recommended
      for treatment of NASH by international guidelines. Lipid lowering agents
      including statins and fibrates, pentoxifylline, angiotensin receptor blockers,
      ursodeoxycholic acid, probiotics and synbiotics are current agents with
      beneficial effects for treatment of NASH but have not been approved yet. Several
      emerging medications are in development for treatment of NASH. Obeticholic acid,
      liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical
      trials or are completing trials. Here in, current and upcoming medications with
      promising results in clinical trial for treatment of NAFLD were reviewed.

PMID- 29204051
TI  - Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key
      players in the pathogenesis of celiac disease.
AB  - Celiac disease (CD) is a chronic immune-mediated disorder triggered by the
      ingestion of gluten in genetically predisposed individuals. Before activating the
      immune system, gluten peptides are transferred by the epithelial barrier to the
      mucosal lamina propria, where they are deamidated by intestinal tissue
      transglutaminase 2. As a result, they strongly bind to human leucocyte antigens
      (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells.
      This induces an inflammatory response, which results in small bowel enteropathy.
      Although gluten is the main external trigger activating both innate and adaptive
      (specific) immunity, its presence in the intestinal lumen does not fully explain
      CD pathogenesis. It has been hypothesized that an early disruption of the gut
      barrier in genetically susceptible individuals, which would result in an
      increased intestinal permeability, could precede the onset of gluten-induced
      immune events. The intestinal barrier is a complex functional structure, whose
      functioning is dependent on intestinal microbiota homeostasis, epithelial layer
      integrity, and the gut-associated lymphoid tissue with its intraepithelial
      lymphocytes (IELs). The aim of this paper was to review the current literature
      and summarize the role of the gut microbiota, epithelial cells and their
      intercellular junctions, and IELs in CD development.

PMID- 29204053
TI  - Induction of precocious intestinal maturation in T-cell deficient athymic
      neonatal rats.
AB  - AIM: To investigate whether gut maturation could be induced precociously in an
      athymic T-cell deficient neonatal rat model. METHODS: Fourteen day-old athymic
      (nude) rats (NIH-Foxn1rnu) were gavaged with either phytohaemagglutinin - a
      lectin from red kidney beans (PHA); trypsin - a protease (Prot); or water -
      vehicle (control) as a single dose on one day or once a day for 3-day. The nude
      rats were either nurtured by their mothers or cross-fostered by conventional
      foster dams of the Sprague-Dawley strain from days 3-5 after birth. At 17 d of
      age, 72 h after administration of the first treatment, intestinal macromolecular
      permeability was tested in vivo, prior to euthanasia, after which blood and gut
      organs were sampled. RESULTS: Provocation with both, PHA and protease, resulted
      in increased gut growth and maturation in nude rat pups independent of nursing.
      Foetal-type enterocytes were replaced by non-vacuolated adult-type enterocytes in
      the distal small intestine epithelium. Decreased intestinal macromolecular
      permeability (gut closure) was observed, with reduced permeability markers (BIgG
      and BSA, P < 0.001) in circulation. Increased pancreatic function, with an
      increased trypsin to protein ratio in pancreas homogenates, was observed
      independent of nursing in the nude pups. Immunostaining showed the presence of a
      few CD3+-cells in the intestinal mucosa of the nude pups. The number of CD3+
      cells remained unaltered by provocation and no differences were observed between
      the nursing sets. Growth and vitality of the nude pups were dependent on
      nurturing, since cross-fostering by conventional dams increased their
      macromolecular absorptive capacity (BSA, P < 0.05), as well as their passive
      immunity (RIgG, P < 0.05). CONCLUSION: Precocious gut maturation can be induced
      by enteral provocation in athymic rat pups, similarly to in euthymic pups, thus
      showing an independence from thymus-derived T-cells.

PMID- 29204052
TI  - Pregnane X receptor and constitutive androstane receptor modulate differently
      CYP3A-mediated metabolism in early- and late-stage cholestasis.
AB  - AIM: To ascertain whether cholestasis affects the expression of two CYP3A
      isoforms (CYP3A1 and CYP3A2) and of pregnane X receptor (PXR) and constitutive
      androstane receptor (CAR). METHODS: Cholestasis was induced by bile duct ligation
      in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls.
      Severity of cholestasis was assessed on histological examination of liver
      sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin.
      Gene and protein expressions of PXR, CAR, CYP3A1 and CYP3A2 were assessed by
      means of qRT-PCR and Western blot, respectively. Alterations in CYP3A activity
      were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam
      hydroxylation, marker reactions for CYP3A enzymes. RESULTS: The mRNA and protein
      expression of CYP3A1 increased significantly in mild cholestasis (P < 0.01). At
      variance, mRNA and protein expression of CYP3A2 didn't change in mild
      cholestasis, whereas the expression and activity of both CYP3A1 and CYP3A2
      decreased dramatically when cholestasis became severe. Consistently with these
      observations, the nuclear expression of both PXR and CAR, which was measured
      because they both translocate into the cell nucleus after their activation,
      virtually disappeared in the late stage of cholestatic injury, after an initial
      increase. These results indicate that early- and late-stage cholestasis affects
      CYP3A-mediated drug metabolism differently, probably as consequence of the
      different activation of PXR and CAR. CONCLUSION: Early- and late-stage
      cholestasis affects CYP3A-mediated drug metabolism differently. PXR and CAR might
      be targeted therapeutically to promote CYP3A-mediated liver detoxification.

PMID- 29204054
TI  - Nuclear heat shock protein 110 expression is associated with poor prognosis and
      hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal
      metastasis.
AB  - AIM: To investigate the significance of heat shock protein 110 (HSP110) in
      gastric cancer (GC) patients with peritoneal metastasis undergoing hyperthermo
      chemotherapy. METHODS: Primary GC patients (n = 14) with peritoneal metastasis or
      positive peritoneal lavage cytology who underwent distal or total gastrectomy
      between April 2000 and December 2011 were enrolled in this study. The patients
      underwent postoperative intraperitoneal hyperthermo-chemotherapy using a
      Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear
      HSP110 expression in surgically resected tumors using immunohistochemistry.
      Additionally, the effect of HSP110 suppression on hyptherthermo-chemosensitivity
      was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437.
      RESULTS: HSP110 immnohistochemical staining in 14 GC patients showed that five
      (35.7%) samples belonged to the low expression group, and nine (64.3%) samples
      belonged to the high expression group. Progression-free survival was
      significantly shorter in the HSP110 high-expression group than in the low
      expression group (P = 0.0313). However, no significant relationships were
      identified between HSP110 expression and the clinicopathological characteristics
      of patients. Furthermore, high HSP110 expression was not an independent
      prognostic factor in GC patients with peritoneal metastasis (P = 0.0625). HSP110
      expression in MKN45 cells was suppressed by KNK437 at the hyperthermic
      temperature of 43  degrees C in vitro. Comparison of MKN45 cell proliferation in
      the presence and absence of KNK437 at 43  degrees C, revealed that proliferation
      was significantly decreased when HSP110 was inhibited by KNK437. Additionally,
      HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to
      hyperthermo-chemotherapy in vitro. CONCLUSION: The expression of nuclear HSP110
      in GC patients might be a new marker of chemosensitivity and a therapeutic target
      for patients who are tolerant to existing hyperthermo-chemotherapies.

PMID- 29204055
TI  - Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated
      radioimmunotherapy and PI3K/mTOR inhibitor.
AB  - AIM: To investigate the therapeutic effect of combined integrin alpha6beta4
      targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic
      cancer model. METHODS: Phosphorylation of Akt, mTOR, the downstream effectors
      eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal
      protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with
      Yttrium-90 (90Y) labeled anti-integrin alpha6beta4 antibody (ITGA6B4) and BEZ235
      by western blotting. The cytotoxic effect of BEZ235 was investigated using a
      colony formation assay. Therapeutic efficacy enhancement by oral BEZ235
      administration was assessed using mice bearing BxPC-3 xenograft tumors. Tumor
      volume measurements and immunohistochemical analyses (cell proliferation marker
      Ki-67, DNA damage marker p-H2AX and p-4EBP1 staining) of tumors were performed
      for evaluation of combined treatment with 90Y-ITGA6B4 plus BEZ235, or each arm
      alone. RESULTS: We found that phosphorylation of Akt (p-Akt), 4EBP1 (p-4EBP1) and
      S6 (p-S6) was inhibited by BEZ235. Colony formation in BxPC-3 cells was
      additively suppressed by the combination of 90Y-ITGA6B4 and BEZ235. Pretreatment
      with BEZ235 before 90Y-ITGA6B4 exposure resulted in significant reduction of
      cells plating efficiency (PE) (0.54 +/- 0.11 vs 2.81 +/- 0.14 with 185 kBq/mL 90Y
      ITGA6B4 exposure, P < 0.01; 0.39 +/- 0.08 vs 1.88 +/- 0.09 with 370 kBq/mL 90Y
      ITGA6B4 exposure, P < 0.01) when 5 * 103 cells per dish were plated. In vivo, the
      combined treatment with 90Y-ITGA6B4 plus BEZ235 enhanced the inhibition of tumor
      growth and statistically significant differences of relative tumor volume were
      observed for 27 d after the treatment start date when compared with the 90Y
      ITGA6B4 single injection treatment (1.03 +/- 0.38 vs 1.5 +/- 0.15 at Day 27, P <
      0.05), and for 41 d when compared with the BEZ235 treatment alone (1.8 +/- 0.7 vs
      3.14 +/- 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction
      in volumes, decreased Ki-67-positive cells, increased p-H2AX-positive cells and
      decreased p-4EBP1 expression. CONCLUSION: The therapeutic efficacy of 90Y-ITGA6B4
      RIT can be improved by combining with dual PI3K and mTOR inhibitor, BEZ235, in a
      pancreatic cancer model suggesting potential clinical application.

PMID- 29204056
TI  - Effects of Hemp seed soft capsule on colonic ion transport in rats.
AB  - AIM: To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion
      transport and its related mechanisms in constipation rats. METHODS: Sprague
      Dawley male rats were randomly divided into three groups: normal group,
      constipation group and HSSC group. Rats in the constipation and HSSC groups were
      administrated loperamide 3 mg/kg per day orally for 12 d to induce the
      constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by
      gavage for 7 d. The normal and constipation groups were treated with distilled
      water. After the treatment, the fecal wet weight and water content were measured.
      The basal short-circuit current (Isc) and resistance were measured by an Ussing
      Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug
      application experiment was also conducted. The accumulative concentrations of
      HSSC (0.1 mg/mL, 0.5 mg/mL, 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 10.0 mg/mL and 25.0
      mg/mL) were added to the normal isolated colonic mucosa and the Isc was recorded.
      Further, after the application of either ion (Cl- or HCO3-) substitution, ion
      channel-related inhibitor (N-phenylanthranilic acid, glybenclamide, 4,4
      diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway
      inhibitor [tetrodotoxin (TTX), atropine, or hexamethonium], the Isc induced by
      HSSC was also measured. RESULTS: In the constipation group, the fecal wet weight
      and the water content were decreased in comparison with the normal group (P <
      0.01). After the treatment with HSSC, the fecal wet weight and the water content
      in the HSSC group were increased, compared with the constipation group (P <
      0.01). In the constipation group, the basal Isc was decreased and resistance was
      increased, in comparison with the normal group (P < 0.01). After the treatment
      with HSSC, the basal Isc was increased (P < 0.05) and resistance was decreased (P
      < 0.01) in the HSSC group compared with the constipation group. In the in vitro
      experiment, beginning with the concentration of 1.0 mg/mL, differences in Isc
      were found between the experimental mucosa (with HSSC added) and control mucosa.
      The Isc of experimental mucosa was higher than that of control mucosa under the
      same concentration (1.0 mg/mL, P < 0.05; 2.5-25 mg/mL, P < 0.01). After the Cl-
      or HCO3- removal and pretreated with different inhibitors (cAMP-dependent and
      Ca2+-dependent Cl- channels, Na+-K+-2Cl- cotransporter (NKCC), Na+-HCO3-
      cotransporter or Cl-/HCO3- exchanger inhibitor), there were differences between
      experimental mucosa and control mucosa; the Isc of experimental mucosa was lower
      than that of control mucosa under the same concentration (P < 0.05). Meanwhile,
      after pretreatment with neural pathway inhibitor (TTX, atropine, or
      hexamethonium), there were no differences between experimental mucosa and control
      mucosa under the same concentration (P > 0.05). CONCLUSION: HSSC ameliorates
      constipation by increasing colonic secretion, which is mediated via the coaction
      of cAMP-dependent and Ca2+-dependent Cl- channels, NKCC, Na+-HCO3- cotransporter
      or Cl-/HCO3- exchanger.

PMID- 29204057
TI  - Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure.
AB  - AIM: To establish a simplified, reproducible D-galactosamine-induced cynomolgus
      monkey model of acute liver failure having an appropriate treatment window.
      METHODS: Sixteen cynomolgus monkeys were randomly divided into four groups (A, B,
      C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine
      at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight,
      respectively, was injected via the small saphenous vein. Vital signs, ICP,
      biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48,
      72, 96, and 120 h after D-galactosamine administration. Progression of clinical
      manifestations, survival times, and results of H&E staining, TUNEL, and Masson
      staining were recorded. RESULTS: Cynomolgus monkeys developed different degrees
      of debilitation, loss of appetite, and jaundice after D-galactosamine
      administration. Survival times of groups A, B, and C were 56 +/- 8.7 h, 95 +/-
      5.5 h, and 99 +/- 2.2 h, respectively, and in group D all monkeys survived the
      144-h observation period except for one, which died at 136 h. Blood levels of
      ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin,
      and inflammatory markers [(tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, and IL-6)] significantly increased compared with baseline values in
      different groups (P < 0.05). Pathological results showed obvious liver cell
      necrosis that was positively correlated with the dose of D-galactosamine.
      CONCLUSION: We successfully established a simplified, reproducible D
      galactosamine-induced cynomolgus monkey model of acute liver failure, and the
      single or divided dosage of 0.25 g/kg is optimal for creating this model.

PMID- 29204058
TI  - Diversity of bacterial lactase genes in intestinal contents of mice with
      antibiotics-induced diarrhea.
AB  - AIM: To investigate the diversity of bacterial lactase genes in the intestinal
      contents of mice with antibiotics-induced diarrhea. METHODS: Following 2 d of
      adaptive feeding, 12 specific pathogen-free Kunming mice were randomly divided
      into the control group and model group. The mouse model of antibiotics-induced
      diarrhea was established by gastric perfusion with mixed antibiotics (23.33 mL.kg
      1.d-1) composed of gentamicin sulfate and cephradine capsules administered for 5
      days, and the control group was treated with an equal amount of sterile water.
      Contents of the jejunum and ileum were then collected and metagenomic DNA was
      extracted, after which analysis of bacterial lactase genes using operational
      taxonomic units (OTUs) was carried out after amplification and sequencing.
      RESULTS: OTUs were 871 and 963 in the model group and control group,
      respectively, and 690 of these were identical. There were significant differences
      in Chao1 and ACE indices between the two groups (P < 0.05). Principal component
      analysis, principal coordination analysis and nonmetric multidimensional scaling
      analyses showed that OTUs distribution in the control group was relatively
      intensive, and differences among individuals were small, while in the model
      group, they were widely dispersed and more diversified. Bacterial lactase genes
      from the intestinal contents of the control group were related to Proteobacteria,
      Actinobacteria, Firmicutes and unclassified bacteria. Of these, Proteobacteria
      was the most abundant phylum. In contrast, the bacterial population was less
      diverse and abundant in the model group, as the abundance of Bradyrhizobium sp.
      BTAi1, Agrobacterium sp. H13-3, Acidovorax sp. KKS102, Azoarcus sp. KH32C and
      Aeromonas caviae was lower than that in the control group. In addition, of the
      known species, the control group and model group had their own unique genera,
      respectively. CONCLUSION: Antibiotics reduce the diversity of bacterial lactase
      genes in the intestinal contents, decrease the abundance of lactase gene, change
      the lactase gene strains, and transform their structures.

PMID- 29204059
TI  - Potential rat model of anxiety-like gastric hypersensitivity induced by
      sequential stress.
AB  - AIM: To establish a rat model of anxiety-like gastric hypersensitivity (GHS) of
      functional dyspepsia (FD) induced by novel sequential stress. METHODS: Animal
      pups were divided into two groups from postnatal day 2: controls and the
      sequential-stress-treated. The sequential-stress-treated group received maternal
      separation and acute gastric irritation early in life and restraint stress in
      adulthood; controls were reared undisturbed with their mothers. Rats in both
      groups were followed to adulthood (8 wk) at which point the anxiety-like
      behaviors and visceromotor responses to gastric distention (20-100 mmHg) and
      gastric emptying were tested. Meanwhile, alterations in several anxiety-related
      brain-stomach modulators including 5-hydroxytryptamine (5-HT), gamma-aminobutyric
      acid (GABA), brain-derived neurotrophic factor (BDNF) and nesfatin-1 in the rat
      hippocampus, plasma and gastric fundus and the 5-HT1A receptor (5-HT1AR) in the
      hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.
      RESULTS: Sequential-stress-treated rats simultaneously demonstrated anxiety-like
      behaviors and GHS in dose-dependent manner compared with the control group.
      Although rats in both groups consumed similar amount of solid food, the rate of
      gastric emptying was lower in the sequential-stress-treated rats than in the
      control group. Sequential stress significantly decreased the levels of 5-HT
      (51.91 +/- 1.88 vs 104.21 +/- 2.88, P < 0.01), GABA (2.38 +/- 0.16 vs 5.01 +/-
      0.13, P < 0.01) and BDNF (304.40 +/- 10.16 vs 698.17 +/- 27.91, P < 0.01) in the
      hippocampus but increased the content of nesfatin-1 (1961.38 +/- 56.89 vs 1007.50
      +/- 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT
      (47.82 +/- 2.29 vs 89.45 +/- 2.61, P < 0.01) and BDNF (257.05 +/- 12.89 vs 536.71
      +/- 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it
      (1391.75 +/- 42.77 vs 737.88 +/- 33.15, P < 0.01); significantly decreased the
      levels of 5-HT (41.15 +/- 1.81 vs 89.17 +/- 2.31, P < 0.01) and BDNF (226.49 +/-
      12.10 vs 551.36 +/- 16.47, P < 0.01) in the gastric fundus but increased the
      content of nesfatin-1 in the same site (1534.75 +/- 38.52 vs 819.63 +/- 38.04, P
      < 0.01). The expressions of 5-HT1AR in the hippocampal CA1 subfield and the
      mucosa of the gastric fundus were down-regulated measured by IHC (Optical Density
      value: Hippocampus 15253.50 +/- 760.35 vs 21149.75 +/- 834.13; gastric fundus
      15865.25 +/- 521.24 vs 23865.75 +/- 1868.60; P < 0.05, respectively) and WB (0.38
      +/- 0.01 vs 0.57 +/- 0.03, P < 0.01) (n = 8 in each group). CONCLUSION:
      Sequential stress could induce a potential rat model of anxiety-like GHS of FD,
      which could be used to research the mechanisms of this intractable disease.

PMID- 29204060
TI  - Post-colonoscopy colorectal cancer rate in the era of high-definition
      colonoscopy.
AB  - AIM: To investigate the post-colonoscopy colorectal cancer (PCCRC) rate for high
      definition (HD) colonoscopy compared with that for standard-definition
      colonoscopy reported previously. METHODS: Using medical records at Sano Hospital
      (SH) and Dokkyo Medical University Koshigaya Hospital (DMUKH), we retrospectively
      obtained data on consecutive patients diagnosed as having CRC between January
      2010 and December 2015. The definition of PCCRC was diagnosis of CRC between 7
      and 36 mo after initial high-definition colonoscopy that had detected no cancer,
      and patients were divided into a PCCRC group and a non-PCCRC group. The primary
      outcome was the rate of PCCRC for HD colonoscopy. The secondary outcomes were
      factors associated with PCCRC and possible reason for occurrence of early and
      advanced PCCRC. RESULTS: Among 892 CRC patients, 11 were diagnosed as having
      PCCRC and 881 had non-PCCRC. The PCCRC rate was 1.7% (8/471) at SH and 0.7%
      (3/421) at DMUKH. In comparison with the non-PCCRC group, the PCCRC group had a
      significantly higher preponderance of smaller tumors (39 mm vs 19 mm, P = 0.002),
      a shallower invasion depth (T1 rate, 25.4% vs 63.6%, P = 0.01), a non-polypoid
      macroscopic appearance (39.0% vs 85.7%, P = 0.02) and an earlier stage (59.7% vs
      90.9%, P = 0.03). Possible reasons for PCCRC were "missed or new" in 9 patients
      (82%), "incomplete resection" in 1 (9%), and "inadequate examination'" in 1 (9%).
      Among 9 "missed or new" PCCRC, the leading cause was non-polypoid shape for early
      PCCRC and blinded location for advanced PCCRC. CONCLUSION: The PCCRC rate for HD
      colonoscopy was 0.7%-1.7%, being lower than that for standard-definition
      colonoscopy (1.8%-9.0%) reported previously employing the same methodology.

PMID- 29204061
TI  - Right- and left-sided colorectal cancers respond differently to traditional
      Chinese medicine.
AB  - AIM: To explore the differences in the responses of left-sided colorectal cancer
      (LSCRC) and right-sided colon cancer (RSCC) to traditional Chinese medicine
      (TCM). METHODS: Patients with postoperative stage I-III colorectal cancer (CRC)
      were enrolled and divided into the LSCRC with or without TCM and RSCC with or
      without TCM groups depending on the primary tumor side and TCM administration.
      Patients in the TCM group were given TCM for at least 6 mo. Our research adopted
      disease-free survival (DFS) as the primary endpoint. We applied a Cox
      proportional hazards regression model for the multivariate factor analysis using
      Stata 12.0 and SPSS 22.0 software for data analysis. RESULTS: Of the 817 patients
      included in our study, 617 had LSCRC (TCM group, n = 404; Non-TCM group, n =
      213), and 200 had RSCC (TCM group, n = 132; Non-TCM group, n = 68). The 6-year
      DFS for patients with LSCRC was 56.95% in the TCM group and 41.50% in the Non-TCM
      group (P = 0.000). For patients with RSCC, the 6-year DFS was 52.92% in the TCM
      group and 37.19% in the Non-TCM group (P = 0.003). Differences between LSCRC and
      RSCC were not statistically significant regardless of TCM ingestion. CONCLUSION:
      Patients with either LSCRC or RSCC and who took TCM experienced longer DFS;
      furthermore, patients with RSCC benefited more from TCM in DFS.

PMID- 29204062
TI  - Hepatitis B virus outreach to immigrant population in Greater Boston Area: Key to
      improving hepatitis B knowledge.
AB  - AIM: To characterize the understanding of hepatitis B virus (HBV) and determine
      if outreach improves HBV understanding among Greater Boston Area immigrants.
      METHODS: Six outreach sessions were held in various community venues in the
      Greater Boston Area. Verbal consent was obtained from participants prior to
      starting each session. Each session included a pre-session questionnaire,
      followed by a teaching session, and then a post-session questionnaire. In person
      interpreters were present for translation during the teaching session and
      assistance for questionnaire completion when needed. The questions were developed
      based on the HBV clinical experience of physicians who serve largely immigrant
      populations. Questionnaires included Likert-type scale, open-ended, and true
      false questions. All results were anonymous. RESULTS: One hundred and one people
      participated in this study. Participants were 30% male with ages ranging from 19
      to 87 years. The study population included immigrants from 21 countries, as well
      as seven United States-born participants. The greatest numbers of participants
      were from Somalia (44%), Morocco (10%), and Cameroon (8%). Pre session
      questionnaires revealed that 42% of participants were unaware that HBV can cause
      cancer, and 50% were unaware that therapies for HBV exist. Our brief teaching
      intervention led to improved scores on post session questionnaires. For example,
      at baseline, 58% of participants responded correctly to the question "HBV
      infection can cause scarring of the liver and liver cancer", whereas 79% of
      participants responded correctly after the teaching session (P = 0.01).
      Furthermore, the mean of total correct answers in the true or false portion of
      the questionnaire increased from 5.5 to 7.6 (P < 0.001). CONCLUSION: A teaching
      session targeting Boston Immigrants at-risk for HBV helped improve scores on HBV
      knowledge questionnaires. Outreach may empower at-risk patients to pro-actively
      seek HBV care.

PMID- 29204063
TI  - Predictors of healthcare-seeking behavior among Chinese patients with irritable
      bowel syndrome.
AB  - AIM: To analyze predictors of healthcare-seeking behavior among Chinese patients
      with irritable bowel syndrome (IBS) and their satisfaction with medical care.
      METHODS: Participating patients met IBS Rome III criteria (excluding those with
      organic diseases) and were enrolled in an IBS database in a tertiary university
      hospital. Participants completed IBS questionnaires in face-to-face interviews.
      The questionnaires covered intestinal and extra-intestinal symptoms, medical
      consultations, colonoscopy, medications, and self-reported response to
      medications during the whole disease course and in the past year. Univariate
      associations and multivariate logistic regression were used to identify
      predictors for frequent healthcare-seeking behavior (>= 3 times/year), frequent
      colonoscopies (>= 2 times/year), long-term medications, and poor satisfaction
      with medical care. RESULTS: In total, 516 patients (293 males, 223 females) were
      included. Participants' average age was 43.2 +/- 11.8 years. Before study
      enrollment, 55.2% had received medical consultations for IBS symptoms. Ordinary
      abdominal pain/discomfort (non-defecation) was an independent predictor for
      healthcare-seeking behavior (OR = 2.07, 95%CI: 1.31-3.27). Frequent colonoscopies
      were reported by 14.7% of patients (3.1 +/- 1.4 times per year). Sensation of
      incomplete evacuation was an independent predictor for frequent colonoscopies (OR
      = 2.76, 95%CI: 1.35-5.67). During the whole disease course, 89% of patients took
      medications for IBS symptoms, and 14.7% reported they were satisfied with medical
      care. Patients with anxiety were more likely to report dissatisfaction with
      medical care (OR = 2.08, 95%CI: 1.20-3.59). In the past year, patients with
      severe (OR = 1.74, 95%CI: 1.06-2.82) and persistent (OR = 1.66, 95%CI: 1.01-2.72)
      IBS symptoms sought medical care more frequently. CONCLUSION: Chinese patients
      with IBS present high rates of frequent healthcare-seeking behavior,
      colonoscopies, and medications, and low satisfaction with medical care.
      Intestinal symptoms are major predictors for healthcare-seeking behavior.

PMID- 29204064
TI  - Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease.
AB  - AIM: To determine the vaccination rates in pediatric immunosuppression-dependent
      inflammatory bowel disease (IBD) and review the safety and efficacy of
      vaccinations in this population. METHODS: The electronic medical records from
      October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age
      or younger and prescribed anti-tumor necrosis factor alpha (anti-TNF-alpha)
      therapy were reviewed for clinical history, medication history, vaccination
      history, and hepatitis B and varicella titers. Literature discussing vaccination
      response in IBD patients were identified through search of the MEDLINE database
      and reviewed using the key words "inflammatory bowel disease", "immunization",
      "vaccination", "pneumococcal", "varicella", and "hepatitis B". Non-human and non
      English language studies were excluded. Search results were reviewed by authors
      to select articles that addressed safety and efficacy of immunizations in
      inflammatory bowel disease. RESULTS: A total of 51 patients diagnosed with IBD
      prior to the age of 10 and receiving anti-TNF-alpha therapy were identified.
      Thirty-three percent of patients (17/51) had incomplete or no documentation of
      vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and
      randomized trials were determined through review of the literature to describe
      the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations
      in adult and pediatric patients with IBD. These studies showed that patients
      safely tolerated the vaccines without significant adverse effects. Importantly,
      IBD patients receiving immunosuppressive medications, particularly anti-TNF-alpha
      treatment, have decreased vaccine response compared to controls. However, the
      majority of patients are still able to achieve protective levels of specific
      antibodies. CONCLUSION: Immunizations have been shown to be well-tolerated and
      protective immunity can be achieved in patients with IBD requiring
      immunosuppressive therapy.

PMID- 29204065
TI  - Anal Cancer and Anal Cancer precursors in Women with a History of HPV-Related
      Dysplasia and Cancer.
AB  - The epidemiology of anal cancer in the U.S. has changed over the past 3 decades.
      During this period the incidence of anal cancer has increased among both men and
      women. Of note, women with a history of anogenital HPV infection are at higher
      risk than the general population for anal cancer. The increased risk ranged from
      increased incidence rate ratios ranging from 1.82 to 6.3 in women with a history
      of cervical cancer, to 4.2-16.4 in women with a history of prior cervical
      intraepithelial neoplasia 3 (CIN 3). In addition, studies describing screening
      women with a previous history of anogential HPV infection (including CIN 3) for
      anal HPV and anal pre-cancers demonstrate that the prevalence of anal HPV is
      measureable in this population. The prevalence of anal high grade squamous
      intraepithelial lesions (HSIL) in this population was relatively low, which may
      have been related to the fact that many of these studies had insufficient
      samples, and the numbers of patients undergoing HRA remain low. Future studies
      evaluating anal cancer screening strategies in this high-risk group are needed.

PMID- 29204066
TI  - Alcohol Use and Sexual Risk Behaviors among Adolescents with Psychiatric
      Disorders: A Systematic Review and Meta-Analysis.
AB  - Adolescents with psychiatric disorders appear to be at increased risk for
      acquiring HIV and other sexually transmitted infections; however, little is known
      about the prevalence of behavioral risk factors in this population. This meta
      analysis aimed to assess the prevalence of alcohol use and sexual risk behaviors
      among adolescents with psychiatric disorders. Electronic database searches
      identified studies sampling adolescents diagnosed with psychiatric disorders and
      assessing both alcohol and sexual risk behaviors. Fourteen studies sampling 3,029
      adolescents with psychiatric disorders were included. The majority of adolescents
      with psychiatric disorders report alcohol use and sexual risk behaviors. Risk
      reduction interventions targeting these two behaviors are needed.

PMID- 29204067
TI  - Heterozygous mutation in OTX2 associated with early-onset retinal dystrophy with
      atypical maculopathy.
AB  - Purpose: Heterozygous mutations in OTX2 have been associated with a range of
      ocular and pituitary abnormalities. We report a novel heterozygous deletion in
      OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Methods:
      Clinical examination included electroretinography and multimodal retinal imaging.
      Molecular genetic testing was composed of next-generation sequencing of a panel
      of retinal dystrophy genes. Results: A now 17-year-old boy presented 12 years
      earlier with a history of progressively poor vision since birth, nyctalopia, and
      early-onset retinal dystrophy with atypical maculopathy. He also had bilateral
      microphthalmos and a slim prepubertal appearance; growth hormone levels were
      within normal ranges. Next-generation sequencing of a retinal dystrophy gene
      panel revealed a heterozygous deletion c.485delC (p.Pro162G.Infs*24) in exon 5 of
      OTX2. Conclusions: This second report of maculopathy associated with a
      heterozygous mutation in OTX2 confirms that mutations in OTX2 should be
      considered in the differential diagnosis of atypical hereditary maculopathy, with
      or without rod-cone dystrophy.

PMID- 29204069
TI  - The Role of Focal Laser in the Anti-Vascular Endothelial Growth Factor Era.
AB  - Introduction: To review important studies examining focal laser for diabetic
      macular edema (DME), to examine real-world data regarding actual treatments
      patients are receiving, to present long-term visual outcomes in real-world
      practice, and to suggest an evidence-based approach for the use of focal laser.
      Methods: This study is a review of landmark studies evaluating focal laser and
      pharmacologic therapy for DME. In addition, the authors include a retrospective
      review of 102 consecutive eyes of 53 patients in our practice setting in rural
      Alabama. A chart review was performed, and patients were included if they were
      diagnosed with DME and were treated with both focal laser and bevacizumab.
      Bevacizumab and focal laser were given on a "as needed basis" at the discretion
      of one treating physician (J.O.M.). Worse visual acuity or worsening macular
      edema were indications for additional treatment. Statistical analysis was
      performed using frequencies and percentages. Best-corrected visual acuity (BCVA)
      was recorded at baseline and at the end of treatment (mean of 5 years) in the
      medical record. Primary outcome measures were BCVA, patients with better than
      20/40 BCVA, patients with worse than 20/200 BCVA, and patients with stable BCVA.
      Results: Anti-vascular endothelial growth factor (VEGF) therapies are the first
      line treatment for DME, but real-world claims data suggest that diabetic patients
      cannot come in for monthly injections as in large clinical trials. In our series,
      after a mean of 5 lasers and 5.5 injections, 90% of eyes had stable or better
      BCVA, 65% were >=20/40, and only 13% were <=20/200. Conclusions: Laser treatment
      for DME remains an important adjunctive therapy.

PMID- 29204068
TI  - alpha-adrenergic agonist brimonidine control of experimentally induced myopia in
      guinea pigs: A pilot study.
AB  - Purpose: To investigate the efficacy of alpha-adrenergic agonist brimonidine
      either alone or combined with pirenzepine for inhibiting progressing myopia in
      guinea pig lens-myopia-induced models. Methods: Thirty-six guinea pigs were
      randomly divided into six groups: Group A received 2% pirenzepine, Group B
      received 0.2% brimonidine, Group C received 0.1% brimonidine, Group D received 2%
      pirenzepine + 0.2% brimonidine, Group E received 2% pirenzepine + 0.1%
      brimonidine, and Group F received the medium. Myopia was induced in the right
      eyes of all guinea pigs using polymethyl methacrylate (PMMA) lenses for 3 weeks.
      Eye drops were administered accordingly. Intraocular pressure was measured every
      day. Refractive error and axial length measurements were performed once a week.
      The enucleated eyeballs were removed for hematoxylin and eosin (H&E) and Van
      Gieson (VG) staining at the end of the study. Results: The lens-induced myopia
      model was established after 3 weeks. Treatment with 0.1% brimonidine alone and
      0.2% brimonidine alone was capable of inhibiting progressing myopia, as shown by
      the better refractive error (p=0.024; p=0.006) and shorter axial length (p=0.005;
      p=0.0017). Treatment with 0.1% brimonidine and 0.2% brimonidine combined with 2%
      pirenzepine was also effective in suppressing progressing refractive error
      (p=0.016; p=0.0006) and axial length (p=0.017; p=0.0004). The thickness of the
      sclera was kept stable in all groups except group F; the sclera was much thinner
      in the lens-induced myopia eyes compared to the control eyes. Conclusions:
      Treatment with 0.1% brimonidine alone and 0.2% brimonidine alone, as well as
      combined with 2% pirenzepine, was effective in inhibiting progressing myopia. The
      result indicates that intraocular pressure elevation is possibly a promising
      mechanism and potential treatment for progressing myopia.

PMID- 29204070
TI  - The characteristics and distribution of dentist workforce in Saudi Arabia: A
      descriptive cross-sectional study.
AB  - Background: The Kingdom of Saudi Arabia has shown steady growth in the dental
      workforce over the last 20 years. Although the number of dental colleges has
      significantly increased in the last decade, there is not any study so far that
      described the status of the licensed dentist workforce in the kingdom. The
      present study aimed to explore the demographic distribution and professional
      characteristics of licensed dentist workforce in Saudi Arabia. Methods: This was
      a descriptive cross-sectional study using the Saudi Commission for Health
      Specialties (SCFHS) database to identify the number of licensed dentists in Saudi
      Arabia as well as their professional and demographic characteristics as of
      December 2016. The data was categorized based on gender, nationality, dental
      specialty, health sector, geographic location, and professional rank. Results:
      The number of licensed dentists working in the kingdom as of December 2016 was
      16887 dentists, and the vast majority of them are professionally registered as
      general dentists (70.27%). The percentage of general dentists among the
      professionally registered female dentists is significantly higher than their male
      counterparts (79.71% vs. 64.80%; P < 0.001). Only 22.08% of the dentists working
      in the kingdom are Saudi. Most of the dentist workforce in the kingdom are male
      (61.06%). The mean age of the Saudi dentists is slightly but significantly
      younger than non-Saudi dentists (37.7 vs. 40.7 years; P < 0.001). Over 80% of the
      Saudi dentists are working in the regions of Riyadh, Makkah, and Eastern
      province. About 66% of the Saudi dentists are working in the public health sector
      in comparison to only 20.46% of the non-Saudi dentists (P < 0.001). Conclusions:
      Most of the dental care in Saudi Arabia is provided by non-Saudi dentists in both
      private and public health sectors. With the rising unemployment rate among Saudi
      dentists, the governmental bodies that are responsible of dental labor market
      regulations such as the ministries of health, economy and planning, and labor
      should come up with a policy to gradually but carefully replace the non-Saudi
      dentists in both public and private sectors with Saudi dentists.

PMID- 29204071
TI  - The pharmaceutical applications of a biopolymer isolated from Trigonella foenum
      graecum seeds: Focus on the freeze-dried matrix forming capacity.
AB  - The aim of the present study was to evaluate the funtion of fenugreek seed
      mucilage (FSM) as potential matrix forming agent for orodispersible
      pharmaceutical lyophilisates. The FSM was isolated and characterized. FSM
      colloidal dispersions were prepared and the rheological evaluation was performed.
      Oral lyophilisates (OLs) with different FSM concentrations, containing meloxicam
      as model drug were prepared by freeze drying method. The OLs were characterized
      and compared to gelatin containing tablets, prepared under the same conditions.
      The FSM dispersions revealed shear thinning flow type. Based on colloidal
      dispersions' rheological properties, five FSM concentrations were taken forward
      to the lyophilization step. Completely dry and elegant tablets were obtained.
      Texture analysis indicated highly porous structures, confirmed by SEM analysis,
      which explain the fast disintegration properties. All the prepared tablets
      disintegrated in less than 47 s. The disintegration process was prolonged by the
      increase in FSM content, due to the high viscosity the polymer creates in aqueous
      media. FSM tablets presented longer disintegration times, as compared to gelatin
      tablets, but also higher crushing strength. Considering the fast disintegration
      and the high crushing strength, FSM is a good candidate as matrix forming agent
      for fast disintegrating dosage forms or other freeze-dried preparations.

PMID- 29204072
TI  - Comparative nutritional value and antimicrobial activities between three
      Euphorbia species growing in Saudi Arabia.
AB  - Plants are excellent sources of nutrition and highly bioactive substances that
      might use in the development of new drugs and pharmaceutical agents. Three
      species of the Genus Euphorbia (Family Euphorpiaceae), namely; Euphorbia
      granulata Forssk, Euphorbia helioscobia L., and Euphorbia hirta Linn growing in
      Ryiadh, KSA were air-dried, powdered, and their active materials were extracted
      with alcohol. The nutritional value phytochemical constituents and antimicrobial
      activity of the plants were determined. The chemical contents were similar in the
      three species; however, lipid profile of the plants showed that the stearic acid
      and lignoceric acid were detected only in E. helioscopia and E. hirta, while
      palmitoleic acid was detected only in E. hirta. The percentage of unsaturated
      fatty acid methyl esters were 52.48%, 69.39% and 66.52% in Euphorbia granulate,
      Euphorbia helioscobia, E. hirta, respectively. Three compounds, 1
      ethoxypentacosane, heptacosan-1-ol and beta-sitosterol were isolated from the
      three plant extracts and identified using different spectroscopic analysis. The
      percentage of crude protein was 43.65%, 25.00% and 18.75% in E. granulata, E.
      helioscobia, and E. hirta, respectively. The free amino acids and amino acid
      composition were quantitatively determined using amino acid analyzer. All the
      plant extracts were active against bacterial and fungal test organisms, however,
      the antimicrobial activity were varied according to both the Euphorbia species
      and the test organism.

PMID- 29204073
TI  - Drive-thru pharmacy service: Assessments of awareness, perception and barriers
      among pharmacists in Jordan.
AB  - Objective: Drive-thru pharmacy services have become widely recognized service
      worldwide. Despite its proven success, there were doubts in its ability to
      maintain safe practice. Thus, the aim of the current study was to investigate the
      awareness, perception and barriers of drive-thru pharmacy services among
      pharmacists in Jordan. Methods: A cross-sectional study was conducted in Amman
      Jordan between February-May 2017. During the study period, 226 pharmacists were
      approached. Pharmacists were interviewed to assess their perception toward drive
      thru services, and to assess their opinions regarding the advantages and
      disadvantages of this system using validated questionnaire. Results: Although the
      majority of pharmacists reported that they were aware about the concept of drive
      thru pharmacy service (n = 194, 85.5%), but only 27.9% (n = 63) reported that
      they are willing to register with this service. The most important advantage of
      drive-thru pharmacy service was serving sick patients, elderly, disabled people
      or women with child in the car (n = 166, 88.0%). Most of pharmacists agreed that
      drive-thru pharmacy service may negatively affect the image of pharmacy
      profession (n = 168, 74.6%), and it makes pharmacists feel more like a fast food
      worker than a pharmacist (n = 147, 65.9%). Pharmacists working in chain community
      pharmacies showed better perception to drive-thru pharmacy service compared to
      pharmacists who are working in independent community pharmacies (p-value =
      0.004). Conclusion: Most of the study pharmacists showed relatively poor
      perception toward drive-thru pharmacy service and were unwilling to use this
      service. More effort is needed to better introduce the concept of drive-thru
      pharmacy service among pharmacists in Jordan since the benefit of this service is
      well established across the world.

PMID- 29204074
TI  - Academic stress-induced changes in Th1- and Th2-cytokine response.
AB  - Psychological stress stimulates physiological responses releasing catecholamines
      and corticoids, which act via corresponding receptors on immune cells, producing
      a shift in the cytokine balance. These responses are variable depending on the
      nature of stressors. The effect of the academic stress on the production of the
      Th1-cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL-2, IL-6 and IL-8) and Th2
      cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students
      after completing their questionnaires was investigated. Blood samples were taken
      at three stages; baseline stage at the beginning, midterm and final academic
      examination stages. Plasma cortisol and cytokines were measured during the three
      stages. The last two stages were compared with the baseline non-stress period.
      Results of the stress induced during the final examination stage were the highest
      with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release
      with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage
      did not show significant reduction in Th1-cytokines except for TNF-alpha, with an
      increase in IFN-gamma level that was reduced in the third stage. Th2 cytokine, IL
      1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-gamma in the
      second stage and IL-6 cytokine in the third stage. Cortisol was positively
      correlated with IL-8 in the last stage and heart rates had negative correlation
      with IL-10 in the first and last stages. Findings of this study indicate that
      exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines.
      In conclusion, Cortisol might have a role in suppressing the release of Th1-
      mediated cellular immune response which could increase the vulnerability among
      the students to infectious diseases.

PMID- 29204075
TI  - Comparative anticancer and antimicrobial activity of aerial parts of Acacia
      salicina, Acacia laeta, Acacia hamulosa and Acacia tortilis grown in Saudi
      Arabia.
AB  - The standardized ethanol extract (EE) of aerial parts of four Acacia species [A.
      salicina (ASEE), A. laeta (ALEE), A. hamulosa (AHEE), and A. tortilis (ATEE)]
      were examined in order to compare their cytotoxic and antimicrobial activities.
      All the extracts were standardized by UPLC- PDA method using rutin as standard
      compound. The extracts ALEE, AHEE and ATEE were found to contain rutin along with
      several other phytoconstituents while rutin was absent in ASEE. All the extracts
      showed varying level of antimicrobial activity with zone of inhibition ranged
      from 11 to 21 mm against Staphylococcus aureus, Escherichia coli, Pseudomonas
      aeruginosa and Candida albicans. The ALEE and ATEE showed relatively high
      antimicrobial potency (MIC = 0.2 to 1.6 mg mL-1) in comparison to other extracts.
      All the extracts were found to reduce the biofilm of P. aeruginosa PAO1 strain
      significantly in comparison to the untreated control. The cytotoxic property of
      ASEE, ALEE, AHEE, ATEE were evaluated against HepG2 (Liver), HEK-293 (Kidney),
      MCF-7 (Breast) and MDA-MB 231 (Breast) cancer cells. Of these, ALEE, AHEE and
      ATEE exhibited moderate cytotoxic property against human liver carcinoma cells
      (HepG2; IC50 = 46.2, 39.2 and 42.3 MUg mL-1, respectively) and breast cancer cell
      lines (MCF-7; IC50 = 57.2, 55.3 and 65.7 MUg mL-1, respectively). The ATEE and
      ALEE showed moderate cytotoxicity against HEK-293 (kidney) cells with IC50 = 49.1
      and 53.5 MUg mL-1, respectively. Since, Acacia species (A. laeta and A. hamulosa)
      contains numerous polyphenols which might prove to be highly cytotoxic and
      antimicrobial agents, we suggest that these species can be further subjected to
      the isolation of more cytotoxic and antimicrobial compounds.

PMID- 29204076
TI  - Editorial: Genomics and Functional Genomics of Stress-mediated Signaling in
      Plants: Volume I.

PMID- 29204077
TI  - A Functional Genomic Perspective on Drought Signalling and its Crosstalk with
      Phytohormone-mediated Signalling Pathways in Plants.
AB  - Introduction: Drought stress is one of the most important abiotic stresses that
      negatively influence crop performance and productivity. Plants acclimatize to
      drought stress conditions through altered molecular, biochemical and
      physiological responses. Gene and/or protein expression and regulation are
      thought to be modulated upon stress perception and signal transduction for
      providing requisite endurance to plants.Plant growth regulators or phytohormones
      are important molecules required for various biological processes in plants and
      are also central to stress signalling pathways. Among various phytohormones,
      Abscisic Acid (ABA) and Ethylene (ET) are considered to be the most vital growth
      regulators implicated in drought stress signalling and tolerance. Besides the
      above two known classical phytohormones, Salicylic Acid (SA) and Jasmonic Acid
      (JA) have also been found to potentially enhance abiotic stress tolerance
      particularly that of drought, salinity, and heat stress tolerance in plants.
      Apart from these several other growth regulators such as Cytokinins (CKs), Auxin
      (AUX), Gibberellic Acid (GA), Brassinosteroids (BRs) and Strigolactones (SLs)
      have also been reported to actively participate in abiotic stress responses and
      tolerance in plants. The abiotic stress signalling in plants regulated by these
      hormones further depends upon the nature, intensity, and duration of exposure to
      various environmental stresses. It has been reported that all these phytohormones
      are also involved in extensive crosstalk and signal transduction among themselves
      and/or with other factors. Conclusion: This review thus summarizes the molecular
      mechanism of drought signalling and its crosstalk with various phytohormone
      signalling pathways implicated in abiotic stress response and tolerance.

PMID- 29204078
TI  - Transcription Factors and Their Roles in Signal Transduction in Plants under
      Abiotic Stresses.
AB  - In agricultural production, abiotic stresses are known as the main disturbance
      leading to negative impacts on crop performance. Research on elucidating plant
      defense mechanisms against the stresses at molecular level has been addressed for
      years in order to identify the major contributors in boosting the plant tolerance
      ability. From literature, numerous genes from different species, and from both
      functional and regulatory gene categories, have been suggested to be on the list
      of potential candidates for genetic engineering. Noticeably, enhancement of plant
      stress tolerance by manipulating expression of Transcription Factors (TFs)
      encoding genes has emerged as a popular approach since most of them are early
      stress-responsive genes and control the expression of a set of downstream target
      genes. Consequently, there is a higher chance to generate novel cultivars with
      better tolerance to either single or multiple stresses. Perhaps, the difficult
      task when deploying this approach is selecting appropriate gene(s) for
      manipulation. In this review, on the basis of the current findings from molecular
      and post-genomic studies, our interest is to highlight the current understanding
      of the roles of TFs in signal transduction and mediating plant responses towards
      abiotic stressors. Furthermore, interactions among TFs within the stress
      responsive network will be discussed. The last section will be reserved for
      discussing the potential applications of TFs for stress tolerance improvement in
      plants.

PMID- 29204080
TI  - Genomics of Metal Stress-Mediated Signalling and Plant Adaptive Responses in
      Reference to Phytohormones.
AB  - Introduction: As a consequence of a sessile lifestyle, plants often have to face
      a number of life threatening abiotic and biotic stresses. Plants counteract the
      stresses through morphological and physiological adaptations, which are imparted
      through flexible and well-coordinated network of signalling and effector
      molecules, where phytohormones play important role. Hormone synthesis, signal
      transduction, perception and cross-talks create a complex network. Omics
      approaches, which include transcriptomics, genomics, proteomics and metabolomics,
      have opened new paths to understand such complex networks. Objective: This review
      concentrates on the importance of phytohormones and enzymatic expressions under
      metal stressed conditions. Conclusion: This review sheds light on gene
      expressions involved in plant adaptive and defence responses during metal stress.
      It gives an insight of genomic approaches leading to identification and
      functional annotation of genes involved in phytohormone signal transduction and
      perception. Moreover, it also emphasizes on perception, signalling and cross
      talks among various phytohormones and other signalling components viz., Reactive
      Oxygen Species (ROS) and Reactive Nitrogen Species (RNS).

PMID- 29204083
TI  - Salinity Tolerance Mechanism of Osmotin and Osmotin-like Proteins: A Promising
      Candidate for Enhancing Plant Salt Tolerance.
AB  - Introduction: Salt stress is one of the most important abiotic stress factors
      which severely affect agricultural production. Osmotins and OLPs (osmotin like
      proteins) are kinds of proteins which were produced during plant adapting to the
      environmental stress. Objective: These proteins were closely related to osmotic
      regulation and resistance stress. They are widely distributed in plants. Their
      expression for these genes was induced by salt stress, which played important
      roles in plants responding to salt stress. Conclusion: During salt stress,
      osmotin can help accumulate proline, and quench reactive oxygen species and free
      radicals.

PMID- 29204079
TI  - An Overview of Signaling Regulons During Cold Stress Tolerance in Plants.
AB  - Plants, being sessile organisms, constantly withstand environmental fluctuations,
      including low-temperature, also referred as cold stress. Whereas cold poses
      serious challenges at both physiological and developmental levels to plants
      growing in tropical or sub-tropical regions, plants from temperate climatic
      regions can withstand chilling or freezing temperatures. Several cold inducible
      genes have already been isolated and used in transgenic approach to generate cold
      tolerant plants. The conventional breeding methods and marker assisted selection
      have helped in developing plant with improved cold tolerance, however, the
      development of freezing tolerant plants through cold acclimation remains an
      unaccomplished task. Therefore, it is essential to have a clear understanding of
      how low temperature sensing strategies and corresponding signal transduction act
      during cold acclimation process. Herein, we synthesize the available information
      on the molecular mechanisms underlying cold sensing and signaling with an aim
      that the summarized literature will help develop efficient strategies to obtain
      cold tolerant plants.

PMID- 29204082
TI  - Looking at Halophytic Adaptation to High Salinity Through Genomics Landscape.
AB  - Soil salinity is an important stress factor that limits plant growth and
      productivity. For a given plant species, it is critical to sense and respond to
      salt stimuli followed by activation of multitude of mechanisms for plants to
      survive. Halophytes, the wonders of saline soils, have demonstrated ability to
      withstand and reproduce in at least 200 mM NaCl concentration, which makes them
      an ideal system to study mechanism of salt adaptation for imparting salt
      tolerance in glycophytes. Halophytes and salt sensitive glycophytes adapt
      different defense strategies towards salinity stress. These responses in
      halophytes are modulated by a well orchestrated network of signaling pathways,
      including calcium signaling, reactive oxygen species and phytohormones. Moreover,
      constitutive expression of salt stress response related genes, which is only salt
      inducible in glycophytes, maintains salt tolerance traits in halophytes. The
      focus of this review is on the adaptive considerations of halophytes through the
      genomics approaches from the point of view of sensing and signaling components
      involved in mediating plant responses to salinity.

PMID- 29204081
TI  - Recent Advances in Substrate Identification of Protein Kinases in Plants and
      Their Role in Stress Management.
AB  - Protein phosphorylation-dephosphorylation is a well-known regulatory mechanism in
      biological systems and has become one of the significant means of protein
      function regulation, modulating most of the biological processes. Protein kinases
      play vital role in numerous cellular processes. Kinases transduce external signal
      into responses such as growth, immunity and stress tolerance through
      phosphorylation of their target proteins. In order to understand these cellular
      processes at the molecular level, one needs to be aware of the different
      substrates targeted by protein kinases. Advancement in tools and techniques has
      bestowed practice of multiple approaches that enable target identification of
      kinases. However, so far none of the methodologies has been proved to be as good
      as a panacea for the substrate identification. In this review, the recent
      advances that have been made in the identifications of putative substrates and
      the implications of these kinases and their substrates in stress management are
      discussed.

PMID- 29204085
TI  - Immune complex negatively regulates toll-like receptor 3-triggered tumour
      necrosis factor alpha production in B cells.
AB  - Inappropriate activation of toll-like receptor 3 (TLR3) has been implicated in
      the pathogenesis of autoimmune diseases, so the negative regulation of TLR3
      triggered immune response has received increasing attention. Nonpathogenic immune
      complex (IC) has been used as treatment for many inflammatory and autoimmune
      diseases. However, the role of IC in the regulation of TLR3-triggered immune
      responses and the underlying mechanisms need to be investigated. In this study we
      demonstrate that IC or intravenous immunoglobulin (Ig) stimulation of B cells
      attenuates polyinosinic:polycytidylic acid (poly I:C)-induced CD40 expression;
      IC, but not Ig, can significantly inhibit poly I:C-induced pro-inflammatory
      tumour necrosis factor alpha (TNF-alpha) production by B cells. Moreover, IC/Ig
      stimulation does not alter the expression of TLR3 in B cells. Further experiments
      suggest that receptor for the Fc portion of IgGIIb (FcgammaRIIb) is involved in
      the suppressive effect of IC on TLR3-mediated TNF-alpha production, but not CD40
      expression. Thus, we provide a new means of negative regulation of TLR3-triggered
      immune responses in B cells via FcgammaRIIb, and we provide a new mechanistic
      explanation of the therapeutic effect of nonpathogenic IC on inflammatory or
      autoimmune diseases.

PMID- 29204084
TI  - Improving Salt Tolerance of Chickpea Using Modern Genomics Tools and Molecular
      Breeding.
AB  - Introduction: The high protein value, essential minerals, dietary fibre and
      notable ability to fix atmospheric nitrogen make chickpea a highly remunerative
      crop, particularly in low-input food production systems. Of the variety of
      constraints challenging chickpea productivity worldwide, salinity remains of
      prime concern owing to the intrinsic sensitivity of the crop. In view of the
      projected expansion of chickpea into arable and salt-stressed land by 2050,
      increasing attention is being placed on improving the salt tolerance of this
      crop. Considerable effort is currently underway to address salinity stress and
      substantial breeding progress is being made despite the seemingly highly-complex
      and environment-dependent nature of the tolerance trait. Conclusion: This review
      aims to provide a holistic view of recent advances in breeding chickpea for salt
      tolerance. Initially, we focus on the identification of novel genetic resources
      for salt tolerance via extensive germplasm screening. We then expand on the use
      of genome-wide and cost-effective techniques to gain new insights into the
      genetic control of salt tolerance, including the responsive genes/QTL(s), gene(s)
      networks/cross talk and intricate signalling cascades.

PMID- 29204086
TI  - Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study.
AB  - This study was conducted to assess the in vivo and ex vivo immunomodulatory
      effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For
      this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral
      dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the
      immunomodulatory effect was assessed on the 6th day following the ingestion. In
      the (non-functional) assessment, the effect of the extract on the body weight,
      relative lymphoid organ weight, splenic cellularity and peripheral blood
      hematologic parameters were evaluated. While in the immunomodulation assessment
      (functional), we investigated the effect of the extract on the proliferative
      capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen
      blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The
      ingestion of M. peregrina extract caused a significant increase in the body
      weight, weight and number of cells of spleen and lymph nodes of the treated mice.
      Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV
      % were increased by the extract treatment in a dose-dependent manner. M.
      peregrina enhanced the proliferative responses of splenic lymphocytes for both T
      cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has
      revealed a T-cell dependent proliferation enhancement in the extract treated
      mice. Moreover, the oral administration of M. peregrina leaves extracts
      significantly increased PFCs/106 splenocytes in a dose-dependent manner. In
      conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant
      potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg.

PMID- 29204087
TI  - The effect of Aeromonas hydrophila infection on the non-specific immunity of
      blunt snout bream (Megalobrama amblycephala).
AB  - Aeromonas hydrophila is the main reason of epidemic septicaemia for freshwater
      fish. In the present study, the effect of Aeromonas hydrophila infection on the
      non-specific immunity of blunt snout bream (Megalobrama amblycephala) was
      studied. After Aeromonas hydrophila challenge, lysozyme activity was
      significantly increased at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d. An increased level
      of lysozyme activity indicated a natural protective mechanism in fish. The
      significant increases of superoxide dismutase activity and catalase activity in
      treatment group were detected at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d after
      Aeromonas hydrophila challenge. Increase in the superoxide anion and H2O2 is
      considered to be beneficial for self-protection from disease. Acid phosphatase
      activity increased significantly at 1 d, 3 d and 5 d after Aeromonas hydrophila
      challenge. Alkaline phosphatase activity in treatment group showed significant
      increase at 4 h, 1 d, 3 d, 5 d, 14 d and 21 d compared to control group.
      Increased phosphatase activity indicates higher breakdown of the energy reserve,
      which is utilized for the growth and survival of fish. These results revealed
      that the non-specific immunity of fish played an important role in self
      protection after pathogens infection.

PMID- 29204088
TI  - Terminally differentiated memory T cells are increased in patients with common
      variable immunodeficiency and selective IgA deficiency.
AB  - Introduction: Previous studies showed that several lymphocyte abnormalities seen
      in the most frequent symptomatic immunoglobulin deficiency, common variable
      immunodeficiency (CVID), were also observed in a genetically related asymptomatic
      disorder - selective IgA deficiency (IgAD). In this study we searched for
      abnormalities in the differentiation stages of T cells as well as for
      similarities of these abnormalities in CVID and IgAD patients. Material and
      methods: Using flow cytometry in 80 patients with IgAD, 48 patients with CVID,
      and 80 control persons we determined T-lymphocyte subsets: both CD4 and CD8 were
      divided into the naive CD45RO-CD27+, early differentiated CD45RO+CD27+, late
      differentiated CD45RO+CD27- and fully differentiated effector CD45RO-CD27- memory
      T cells, as well as Treg cells, defined as CD4+CD25highCD127low T cells. Results:
      An increase of CD4+ and CD8+ late differentiated memory cells was observed
      comparing CVID patients to controls, as well as comparing IgAD patients to
      controls. In CVID patients an increase of CD4+ early differentiated memory cells,
      a decrease of CD8+ intermediate memory cells, and CD4+ and CD8+ naive cells were
      found as well. The abnormalities in IgAD patients might be explained by higher
      CMV seropositivity observed in our IgAD. We confirmed the repeatedly published
      decrease of Treg cells in CVID patients, while Treg cells in IgAD patients were
      increased compared to controls. Conclusions: Our results show T-cell activation
      not only in CVID, but also in IgAD patients. The increase in IgAD patients may be
      influenced by a more frequent CMV infection in our group of IgAD patients.

PMID- 29204089
TI  - Subpopulations of natural killer-T-like cells before and after surgical treatment
      of laryngeal cancer.
AB  - Introduction: Tumours connected with head and neck comprise about 5% of all
      tumours. The most frequent histological type of laryngeal carcinoma is squamous
      cell carcinoma. Different research projects suggest that the role of T
      lymphocytes might be significant in tumour development. iNKT cells are a new
      subpopulation of T cells and show cytotoxic activity against tumours. iNKT cells
      participate in modulating the function of other cells which have anti-tumour
      properties and secrete cytokines, which have pro-inflammatory and anti
      inflammatory effects. In animal models the significance of iNKT cells in various
      diseases including cancer was shown. Aim of the study: The aim of this study was
      to determine the percentages of iNKT cells, CD161+ cells, CD161- cells, iNKT CD4+
      cells, and iNKT CD8+ cells, NK cells, NKT-like cells, and T cells subsets present
      in peripheral blood of patients with laryngeal cancer before and two months after
      the tumour resection, in comparison to healthy volunteers. Materials and methods:
      This study included material from laryngeal patients who were treated at the
      Department of Otolaryngology and Laryngological Oncology (Medical University of
      Lublin) between 2012 and 2013. A total of 50 patients (40 men and 10 women) aged
      between 45 and 77 years (median age: 60 years) were enrolled. Based on the TNM
      classification, the patients were classified as having stage I-IV laryngeal
      cancer. The control group was composed of 15 healthy volunteers (12 men and three
      women) aged between 43 and 82 years (median age: 61 years). The protocol of the
      study was approved by the Local Bioethical Committee at the Medical University of
      Lublin.Peripheral blood samples (15 ml) from the basilic vein were collected by
      venipuncture using sterile, sodium heparin-treated tubes (20 units per ml of
      blood) and used for cytometric analyses. Results: iNKT cells were analysed among
      T CD3+ cells. The percentage of CD3+ and CD3+CD4+ T cells before tumour resection
      was higher than in the control group, but the increase of CD3+ T cells was not
      significant. The T CD3+CD4+ / T CD3+CD8+ cell ratio was significantly higher than
      in healthy donors. After tumour resection a decreased percentage of CD3+CD4+ T
      cells but an increased percentage of CD8+CD3+T cells was noted. The T CD3+CD4+ /
      T CD3+CD8+ cell ratio was significantly higher in patients before and after the
      surgery than in the control group. The amount of NKT-like cells increased after
      resection and was significantly higher than in the control group. Conclusions:
      Our study exhibited the change in percentage of iNKT, NK, NKT-like cells, and T
      lymphocytes after tumour resection in patients with laryngeal cancer. The
      research explains the contribution of those cells in immunological response
      against tumour.

PMID- 29204090
TI  - Autoantibodies, C-reactive protein, erythrocyte sedimentation rate and serum
      cytokine profiling in monitoring of early treatment.
AB  - Introduction: Currently used clinical scale and laboratory markers to monitor
      patients with early rheumatoid arthritis (RA) seem to be not sufficient. It has
      been demonstrated that disease- related cytokines may be elevated very early in
      RA development and cytokines are considered as the biomarkers potentially useful
      for RA monitoring. Material and methods: The group of patients with
      undifferentiated arthritis (UA) developing RA (UA->RA) was identified from a
      total of 121 people with arthralgia. UA->RA (n = 16) and healthy control (n = 16)
      subjects underwent clinical and laboratory evaluation, including acute phase
      reactants (APRs) and autoantibodies. Cytokines IFN-gamma, IL-10, TNF, IL-17A, IL
      6, IL-1b, IL-2 in sera were assayed using flow cytometric bead array test.
      Results: 34.5% of patients with UA developed RA. DAS28 reduced as early as 3
      months after initiation of treatment. No DAS28 difference between groups of
      autoantibody (RF, anti-CCP, ANA-HEp-2) -positive and -negative patients was
      observed, however, comparing groups of anti-CCP and RF-double negative and 
      double positive patients, the trend of sooner clinical improvement was visible in
      the second abovementioned group. After the treatment introduction, the ESR level
      reduced significantly, while CRP level reduction was not significant. Serum
      cytokine levels of IL-10, IL-6 and IL-17A reduced after 6 months since
      introduction of treatment. The positive correlations between ESR, CRP and
      specific cytokine levels were observed. Conclusions: The autoantibody and APR
      profile is poorly connected with the RA course. The serum cytokine profile change
      in the course of RA and may be potentially used for optimization of RA
      monitoring.

PMID- 29204091
TI  - Lipocalin 2 as a clinical significance in rheumatoid arthritis.
AB  - Aim of the study: In this study, serum lipokalin 2 (LCN-2) levels and its
      clinical and radiological significance in patients with rheumatoid arthritis was
      evaluated. Material and methods: The study enrolled 37 patients with RA and 34
      healthy controls. Serum LCN-2 level was measured using ELISA method. Patients
      with DAS 28 scores <= 3.2, and > 3.2 were allocated into lower and high/moderate
      disease activity groups, respectively. Additionally patients were divided into 2
      groups as early RA (disease duration <= 2 years) and established RA (duration of
      the disease >= 2 years). Functional disability was evaluated using Health
      Assessment Questionnaire (HAQ). Radiographs were scored using the modified Larsen
      score. Results: Serum LCN-2 (p = 0.029) levels were significantly higher in
      patients with RA than in the controls. Serum LCN-2 level did not correlate with
      laboratory and clinical parameters of disease activity like erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), DAS 28, Health Assessment
      Questionnaire Score (HAQ) and Nottingham Health Profile (NHP). Similarly, any
      correlation could not be found between structural joint damage and serum LCN2
      levels. Conclusions: These results indicate that serum LCN-2 levels may be used
      as an indicator for structural damage like erosions in the early stage of the
      disease but do not able to be used to monitor disease activity.

PMID- 29204092
TI  - Effect of perinatal risk factors on neutrophil gelatinase-associated lipocalin
      (NGAL) level in umbilical and peripheral blood in neonates.
AB  - Introduction: Acute kidney injury biomarkers are opening a new era in diagnosing
      kidney failure. The requirement for a specific and sensitive marker of kidney
      function is highly desirable in neonates because the diagnostic possibilities in
      this age group are not sufficient. Recent research show that neutrophil
      gelatinase-associated lipocalin (NGAL) can have a great potential but there is a
      wide range of medical conditions, that may influence their expression. The aim of
      the study: was to evaluate the impact of perinatal risk factors on NGAL level in
      neonates. Material and methods: NGAL was measured in umbilical cord blood and
      peripheral blood in full term neonates with perinatal risk factors during the
      first days of life. Results: We found significantly higher umbilical cord blood
      NGAL levels in neonates with perinatal risk factors (117.69 ng/ml) compared to
      the control group (64.37 ng/ml). No significant difference in peripheral blood
      NGAL level was shown between the two groups. Umbilical cord blood NGAL level
      correlated positively with peripheral blood NGAL level (r = 0.36, p < 0.01).
      Umbilical cord blood NGAL level was significantly higher in neonates with fetal
      distress and infection compared to neonates with other perinatal risk factors.
      Peripheral blood NGAL level was significantly higher in neonates with infection
      compared to neonates with other perinatal risk factors. Significantly higher
      umbilical cord blood NGAL levels were seen in neonates born by operative delivery
      compared to born by natural delivery.

PMID- 29204093
TI  - Evaluation of the adenosine deaminase (ADA) G22A gene polymorphism with recurrent
      spontaneous abortion among Egyptian patients.
AB  - Introduction: Adenosine and deoxyadenosine metabolism is influenced by adenosine
      deaminase (ADA) enzyme. ADA increases in different diseases and is considered as
      one of the markers for cell-mediated immunity. Pregnancy is associated with
      depressed cell-mediated immunity. The level of ADA expression, which seems to
      play a key role in maintaining pregnancy, is influenced by adenosine deaminase
      G22A gene polymorphism. We aimed in our study to evaluate the association of ADA
      G22A gene polymorphism with recurrent spontaneous abortion (RSA) in Egyptian
      women. Material and methods: Adenosine deaminase G22A gene polymorphism was
      genotyped in 40 patients (age range 22-39 years) with a history of RSA, selected
      from those attending the Gynaecology and Obstetrics Clinic of Beni-Suef
      University Hospital, and 20 age-matched healthy women as a control group, using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. Results: In our study, no statistically significant difference was
      found between RSA patients and control group as regards ADA G22A genotypes (p =
      0.653) and alleles (p = 0.697). A comparison of the frequencies of ADA alleles in
      RSA patients as regards the below-35-years-old age group revealed that ADA 2(A)
      allele was associated with a low risk for RSA in patients aged 35 years old or
      younger (p = 0.008). Conclusions: In conclusion, our study revealed an age
      dependent protective value of ADA 2(A) allele in recurrent spontaneous abortions
      among the Egyptian population.

PMID- 29204094
TI  - The significance of IL-1beta +3953C>T, IL-6 -174G>C and -596G>A, TNF-alpha 
      308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of
      IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of
      gestation.
AB  - Introduction: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that
      affects primarily preterm infants. Genetic factors are also taken into
      consideration in the pathogenesis of BPD. Genetic predispositions to higher
      production of inflammation mediators seem to be crucial. Material and methods:
      The aim of this study was to evaluate the possible relationship between
      polymorphisms: interleukin-1beta +3953 C>T, interleukin-6 -174 G>C and -596 G>A,
      tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence
      of BPD in a population of 100 preterm infants born from singleton pregnancy,
      before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and
      without congenital abnormalities. Results: In the study population BPD was
      diagnosed in 36 (36%) newborns. Among the studied polymorphisms we found the
      higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842
      [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658
      8.706]) and CC IL-6 -174G>C (1.6 [0.315-8.314]) and GA (2.753 [0.828-10.64]) and
      AA (1.5 [0.275-8.067] IL-6 -596G>A), GA 1.509 (0.515-4.301) TNF-alpha -308G>A.
      However, these finding were not statistically significant. Conclusions: Genetic
      factors are undeniably involved in the pathogenesis of BPD. In the times of
      individualised therapy finding genes responsible for BPD might allow the
      development of new treatment strategies. A new way of specific therapy could
      ensure the reduction of complications connected with BPD and treatment costs.

PMID- 29204095
TI  - Immune disorders in anorexia.
AB  - Anorexia nervosa is a disease involving eating disorders. It mainly affects young
      people, especially teenage women. The disease is often latent and occurs in many
      sub-clinical and partial forms. Approximately from 0.3% to 1% of the population
      suffers from anorexia. It has been shown that patients with anorexia develop
      neurotransmitter-related disorders, leading to uncontrolled changes in the immune
      and endocrine systems. Interactions between cytokines, neuropeptides, and
      neurotransmitters play an important role in disease development. Significant
      malnutrition induces disorders and alterations in T-cell populations. The
      cellular response in patients with anorexia nervosa has been shown to be normal,
      although opinions on this issue are controversial. Laboratory studies on
      neutrophils in anorexia patients showed decreased adhesion and reduced
      bactericidal and cell activities. Despite such unfavourable results, patients
      with anorexia are resistant to infections, which are very rare in this group.
      Glutamine improves the performance of the human immune system. The administration
      of glutamine to anorexia patients, as a supplement to parenteral nutrition, has
      resulted in significant improvements in immune system parameters. The results of
      previous studies on the causes and risk factors in the development of anorexia
      nervosa are still ambiguous. One can hope that the differences and similarities
      between patients with anorexia nervosa and those with other forms of protein
      calorie malnutrition may be helpful in determining the relationship between
      nutritional status and body defences and susceptibility to infection, and can
      help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

PMID- 29204096
TI  - Interference RNA in immune-mediated oral diseases - minireview.
AB  - Immune-mediated oral disorders are characterised by their chronicity, and some
      are refractory to treatment. Interference RNA (iRNA) has been implicated in the
      underlying mechanism of such immune-mediate oral and refractory inflammatory oral
      diseases. iRNA-based understanding of the mechanism in these diseases may help to
      produce non-invasive diagnostic methodologies and treatment modalities of such
      drug non-responsive diseases. Oral lesions in these immune-mediated diseases can
      precede the occurrence of lesions in other regions of the body. The early
      diagnosis and treatment of these drug non-responsive diseases might benefit the
      patient by reducing chronicity and probably even resolving the disease. This aim
      of the present minireview is to give an overview of the possible implications of
      iRNA on the pathogenesis, diagnosis, and treatments of immune-mediated and
      inflammatory oral diseases. The manuscript can form the framework for research on
      iRNA in these immune-mediated oral disorders.

PMID- 29204098
TI  - Effectiveness of rituximab in nephrotic syndrome treatment.
AB  - Idiopathic nephrotic syndrome (INS) is a common chronic illness characterized by
      massive proteinuria and hypo-albuminemia in children. Baseline treatment is 6
      month-corticotherapy. In cases of steroid resistant/dependent INS several types
      of treatment are used, including course of methyloprednisolone "pulses",
      alkylating agents, cyclosporin A, levamisole and mycophenolate mofetil. It has
      been suggested that children with frequently relapsing nephrotic syndrome or
      steroid-dependent nephrotic syndrome had a significantly longer relapse-free
      period if rituximab (RTX) treatment was additionally applied. We present a case
      of a 4.5 boy who due to steroid-sensitive, steroid-dependent nephrotic syndrome
      has been successfully treated with RTX. Administration of the one dose of
      Rituximab in the patient caused immediate decrease of CD19/CD20 positive B
      lymphocyte population. The depletion of B cells has been observed for the next
      six months. With regard to the fact that RTX treatment may affect patient's
      immune response, comprehensive immunodiagnostic has been conducted in a course of
      the Therapy.

PMID- 29204097
TI  - Air pollution, oxidative stress, and exacerbation of autoimmune diseases.
AB  - A number of epidemiological studies have shown a strong association between
      exposure to ambient airborne particulate matter (PM 2.5, PM < 1.0) and lung or
      cardiovascular diseases characterised by high mortality and morbidity. However,
      much less is known about the role of air pollution in the pathogenesis of
      autoimmune diseases, which constitutes a significant problem in modern society.
      This paper summarises the state of current research regarding the influence of PM
      on the development and/or progression of autoimmune diseases. A brief review of
      the great body of research concerning pathogenesis of autoimmune disorders is
      presented. Then, the scope of our review is narrowed to the research related to
      the impact of particulate matter on oxidative and nitrosative stress, as well as
      exacerbation of chronic inflammation, because they can contribute to the
      development of autoimmune diseases. Moreover, we discuss the impact of various
      components of PM (metal, organic compounds) on PM toxicity and the ability to
      generate oxidants.

PMID- 29204099
TI  - Tuberculosis infection in children with proteinuria/nephrotic syndrome.
AB  - Children with nephrotic syndrome (NS) are at greater risk of infections than the
      general population, due to immunodeficiency in the course of the disease and the
      treatment. In this study we present 4 children (2 girls, 2 boys), mean age 7.6 +/
      5.1 years, with NS/proteinuria and latent tuberculosis in 3 children and lymph
      node tuberculosis in 1 child. The reasons for testing these children for
      tuberculosis (TB) were the evaluation of the epidemiological status before
      treatment with corticosteroids (GCS), leukopenia and the relapse of NS, and non
      nephrotic proteinuria. The diagnosis of TB infection was based on positive IGRA
      (Interferon-Gamma Release Assay). Chest X-ray was normal in all the children.
      Chest CT scan revealed an enlargement of lymph nodes in 1 child. The children
      were treated with isoniazid (3 children) and isoniazid, rifampicin and
      pyrazinamide (1 child). Three children with idiopathic nephrotic syndrome were
      treated with prednisone. The child with non-nephrotic proteinuria was treated
      with enalapril. Proteinuria disappeared in all children during anti-TB treatment.

PMID- 29204100
TI  - Interaction and cellular uptake of surface-modified carbon dot nanoparticles by
      J774.1 macrophages.
AB  - Carbon dot (Cdot) nanoparticles are an emerging class of carbon nanomaterials
      with a promising potential for drug delivery and bio imaging applications.
      Although the interaction between Cdots and non-immune cell types has been well
      studied, Cdot interactions with macrophages have not been investigated. Exposure
      of Cdot nanoparticles to J774.1 cells, a murine macrophage cell line, resulted in
      minimal toxicity, where notable toxicity was only seen with Cdot concentrations
      higher than 0.5 mg/ml. Flow cytometric analysis revealed that Cdots prepared from
      citric acid were internalized at significantly higher levels by macrophages
      compared with those prepared from bamboo leaves. Interestingly, macrophages
      preferentially took up phenylboronic acid (PB)-modified nanoparticles. By
      fluorescence microscopy, strong blue light-specific punctate Cdot fluorescence
      resembling Cdot structures in the cytosolic space was mostly observed in J774.1
      macrophages exposed to PB-modified nanoparticles and not unmodified Cdot
      nanoparticles. PB binds to sialic acid residues that are overexpressed on
      diseased cell surfaces. Our findings demonstrate that PB-conjugated Cdots can be
      taken up by macrophages with low toxicity and high efficiency. These modified
      Cdots can be used to deliver drugs to suppress or eliminate aberrant immune cells
      such as macrophages associated with tumors such as tumor-associated macrophages.

PMID- 29204101
TI  - Lymphoepithelial carcinoma: a case report of a rare tumor of the larynx.
AB  - Background: Lymphoepithelial carcinoma is a tumor mostly diagnosed in the
      nasopharynx, but it has also been described in a variety of nonnasopharyngeal
      sites. It is extremely rare in the larynx and should be distinguished from
      squamous cell carcinoma. Therefore, it must be known by clinicians, pathologists
      and oncologists. In this case report, we discuss its etiopathogeny, its
      epidemiological, clinical, pathological and therapeutic aspects, and its outcome.
      Case presentation: An 81-year-old Morrocan man, smoker for 40 years, presented
      with a 1 year history of dysphonia, dyspnea and dysphagia. Laryngoscopy showed a
      mass occupying supraglottic, glottic and subglottic levels of the larynx. Cervico
      thoracic computed tomography scan showed a laryngeal wall thickening with
      cervical lymphadenopathy. Laryngeal biopsy was performed. Microscopic analysis
      and immunohistochemistry confirmed the diagnosis of laryngeal lymphoepithelial
      carcinoma. Immunostaining for LMP1 was negative. Conclusion: Laryngeal
      lymphoepithelial carcinoma is an extremely rare and an aggressive tumor. It is
      rarely associated with the EBV. It must be regarded as a distinct entity.
      Radiotherapy is advisable as the unique therapy for local tumor. A correct
      diagnosis and a close collaboration between the pathologist and clinicians is
      mandatory for an optimal treatment strategy.

PMID- 29204102
TI  - Diagnostic accuracy of touch imprint cytology for head and neck malignancies: a
      useful intra-operative tool in resource limited countries.
AB  - Background: Intraoperative consultation is an important tool for the evaluation
      of the upper aerodigestive tract (UAT) malignancies. Although frozen section
      analysis is a preferred method of intra-operative consultation, however in
      resource limited countries like Pakistan, this facility is not available in most
      institutes; therefore, we aimed to evaluate the diagnostic accuracy of touch
      imprint cytology for UAT malignancies using histopathology of the same tissue as
      gold standard. Methods: The study involved 70 cases of UAT lesions operated
      during the study period. Intraoperatively, after obtaining the fresh biopsy
      specimen and prior to placing them in fixative, each specimen was imprinted on 4
      6 glass slides, fixed immediately in 95% alcohol and stained with Hematoxylin and
      Eosin stain. After completion of the cytological procedure, the surgical biopsy
      specimen was processed. The slides of both touch Imprint cytology and
      histopathology were examined by two consultant histopathologists. Results: The
      result of touch imprint cytology showed that touch imprint cytology was
      diagnostic in 68 cases (97.1%), 55 (78.6%) being malignant, 2 cases (2.9%) were
      suspicious for malignancy, 11 cases (15.7%) were negative for malignancy while 2
      cases (2.9%) were false negative. Amongst the 70 cases, 55 cases (78.6%) were
      malignant showing squamous cell carcinoma in 49 cases (70%), adenoid cystic
      carcinoma in 2 cases (2.9%), non-Hodgkin lymphoma 2 cases (2.9%), Mucoepidermoid
      carcinoma 1 case (1.4%), spindle cell sarcoma in 1 case (1.4%). Two cases (2.9%)
      were suspicious of malignancy showing atypical squamoid cells on touch imprint
      cytology, while 13 cases (18.6%) were negative for malignancy, which also
      included 2 false negative cases. The overall diagnostic accuracy of touch imprint
      cytology came out to be 96.7% with a sensitivity and specificity of 96 and 100%,
      respectively while PPV and NPV of touch imprint cytology was found to be 100 and
      84%, respectively. Conclusion: Our experience in this study has demonstrated that
      touch imprint cytology provides reliable specific diagnoses and can be used as an
      adjunct to histopathology, particularly in developing countries, where the
      facility of frozen section is often not available, since a rapid preliminary
      diagnosis may help in the surgical management planning.

PMID- 29204103
TI  - Single mothering as experienced by Burundian refugees in Australia: a qualitative
      inquiry.
AB  - Background: Refugee mothers have fled from their homeland to escape persecutions
      with their children only to find other threats to their well-being in the new
      country. Building on previous research, it is known that being a new immigrant is
      challenging and requires adaptation. The adaptation process, known as
      acculturation, may not be successful leading to psychological distress. It is
      also known that a generation gap can occur when children acculturate faster than
      their parents. What was lacking was understanding about the experiences of single
      refugee mothers. Methods: Interpretative phenomenological study was undertaken to
      explore the lived experiences of eight Burundian refugee single mothers in
      Australia. Data were collected by in-depth interviews. Each interviews were
      transcribed and analyzed using thematic analysis. Results: Findings revealed
      three themes. First theme 'Traditional mothering practices of Burundian culture'
      illustrated mothering strategies as practiced prior to their arrival in Australia
      including mothering with sufficient social support, strong position of parents,
      and regular use of physical disciplining. Second theme 'Challenges identified
      after arrival to new country' revealed that mothers felt their children
      acculturated faster than themselves which led to intergenerational gap. This has
      also led participants to live in a continuous dilemma, experiencing inner
      conflicts and struggles associated with their mothering practices, especially
      when mothers had arrived with a lack of knowledge relating to acceptable
      mothering practices in a new culture. Final theme, 'Reforming family life in
      Australia' highlighted the decisions made by single refugee mothers which is to
      embrace both new and original cultures, leading to successful acculturation.
      However, lack of appropriate knowledge of acceptable mothering practices led to
      involvement of legal authorities who threatening to remove children from the
      mother's care. This has led mothers feeling change of power from 'mother to
      child, 'to child to mother', raises concerns for family wellbeing. Conclusions: A
      need for parenting information when entering a new country including education
      about any legal obligations for parents such as a Child Protection Act will
      assist successful acculturation. As nurses are likely to encounter refugee single
      mothers, they are well placed to provide support and education to new refugee
      single mothers.

PMID- 29204104
TI  - Assessing the Consultation and Relational Empathy (CARE) Measure in sexual health
      nurses' consultations.
AB  - Background: Increasingly healthcare policies emphasise the importance of person
      centred, empathic care. Consequently, healthcare professionals are expected to
      demonstrate the 'human' aspects of care in training and in practice. The
      Consultation and Relational Empathy (CARE) Measure is a patient-rated measure of
      the interpersonal skills of healthcare practitioners. It has been widely
      validated for use by healthcare professionals in both primary and secondary care.
      This paper reports on the validity and reliability of the CARE Measure with
      sexual health nurses. Methods: Patient questionnaires were collected for 943
      consultations with 20 sexual health nurses. Participating patients self-completed
      the questionnaire immediately after the encounter with the nurse. The
      questionnaire included the ten item CARE Measure, the Patient Enablement Index,
      and overall satisfaction instruments. Construct validity was assessed through
      Spearman's correlation and principal component analysis. Internal consistence was
      assessed through Cronbach's alpha and the inter-rater reliability through
      Generalisability Theory. Data were collected in 2013 in Scotland. Results: Female
      patients completed 68% of the questionnaires. The mean patient age was 28.8 years
      (standard deviation 9.8 years). Two of the 20 participating nurses withdrew from
      the study. Most patients (71.7%) regarded the CARE Measure items as very
      important to their consultation and the number of 'not applicable' and missing
      responses' were low (2.6% and 0.1% respectively). The participating nurses had
      high CARE Measure scores; out of a maximum possible score of 50, the overall mean
      CARE measure score was 47.8 (standard deviation 4.4). The scores were moderately
      correlated with patient enablement (rho = 0.232, p = 0.001) and overall
      satisfaction (rho = 0.377, p = 0.001. Cronbach's alpha showed the measure's high
      internal consistency (Cronbach's alpha coefficient = 0.95), but the inter-rater
      reliability could not be calculated due to the high achieved CARE Measure scores
      that varied little between nurses. Conclusions: Within this clinical context the
      CARE Measure has high perceived relevance and face validity. The findings support
      construct validity and some evidence of reliability. The high CARE Measure scores
      may have been due to sample bias. A future study which ensures a representative
      sample of patients on a larger group of nurses is required to determine whether
      the measure can discriminate between nurses.

PMID- 29204105
TI  - Treatment with 24 h-delayed normo- and hyperbaric oxygenation in severe sepsis
      induced by cecal ligation and puncture in rats.
AB  - Background: Septic shock remains a leading cause of death worldwide. Hyperbaric
      oxygen treatment (HBO2) has been shown to alter the inflammatory response during
      sepsis and to reduce mortality. A therapeutic window of HBO2 treatment has been
      demonstrated experimentally, but optimal timing remains uncertain. We
      investigated the effects of 24 h delayed normobaric oxygen (NBO2) and HBO2
      treatment on the endogenous production of the inflammatory markers interleukin
      (IL)-6, tumor necrosis factor (TNF)-alpha and IL-10, and on mortality in rats
      with cecal ligation and puncture (CLP) induced sepsis. Method: Fifty-five male
      Sprague-Dawley rats underwent CLP and were randomized to the following groups: 1)
      HBO2 2.5 bar absolute pressure (pabs); 2) NBO2 1.0 bar pabs; 3) Control (no
      treatment), and they were individually monitored for 72 h with intermittent blood
      sampling. Results: IL-6, TNF-alpha, and IL-10 were increased 24 h after the
      procedure, and IL-6 was significantly higher in non-survivors than in survivors.
      The level of IL-10 was significantly higher at hour 48 in the HBO2 group compared
      to control (p = 0.01), but this was not the case at other time points. No other
      significant differences in cytokine levels were found for any group comparisons.
      Delayed NBO2 and HBO2 treatment failed to change the mortality in the animals.
      Conclusion: High levels of IL-6 in non-surviving animals with sepsis suggest that
      IL-6 is a potential biomarker. We found a significantly higher concentration of
      IL-10 in the HBO2 group at hour 48 vs. control animals. However, 24 h-delayed
      treatment with HBO2 did not change the levels of pro-inflammatory cytokines and
      survival, suggesting that earlier intervention may be required to obtain an anti
      inflammatory effect.

PMID- 29204106
TI  - Morbidity dynamics in proton-photon or photon radiation therapy for locally
      advanced prostate cancer.
AB  - Aim: This study evaluated the frequency and long-term dynamics of early and late
      post irradiation damage after proton-photon or photon therapy for locally
      advanced prostate cancer. Background: The results of a randomized study of proton
      photon or photon therapy using several fractionation regimes were analyzed in 272
      patients with high and intermediate risk of progression. Materials and methods:
      Three variants of proton boost fractionation were studied sequentially: 3.0 (8
      daily fractions), 4.0 (5 fractions, 3 or 5 fractions/week), and 5.5 (3 fractions,
      3 fractions/week) Gy(RBE). Results: A significant decrease in the severity of
      both acute and late gastrointestinal injuries is achievable with a proton beam.
      The dynamics of late gastrointestinal and genitourinary toxicity over a 10-year
      period were generally characterized by a decrease in severity of morbidity by 30%
      and 15%, respectively. Conclusions: Local irradiation with a fractional dose of
      3.0-5.5 Gy(RBE) and a cumulative dose of 28.0-28.8 Gy(RBE) for protons
      significantly reduces the early and late rectitis severity, but does not reduce
      the risk of lower urinary tract injuries. Fractionation regimens do not
      significantly differ in toxicity levels.

PMID- 29204107
TI  - Use of Cyclic Backbone NGR-Based SPECT to Increase Efficacy of Postmyocardial
      Infarction Angiogenesis Imaging.
AB  - As CD13 is selectively expressed in angiogenesis, it can serve as a target for
      molecular imaging tracers to noninvasively visualize angiogenic processes in
      vivo. The CD13-targeting moiety NGR was synthesized and cyclized by native
      chemical ligation (NCL) instead of disulfide bridging, leading to a cyclic
      peptide backbone: cyclo(Cys-Asn-Gly-Arg-Gly) (coNGR). Beside this new monomeric
      coNGR, a tetrameric NGR peptide co(NGR)4 was designed and synthesized. After
      radiolabeling, their in vitro and in vivo characteristics were determined. Both
      coNGR-based imaging agents displayed considerably higher standardized uptake
      values (SUVs) at infarcted areas compared to the previously reported disulfide
      cyclized cNGR imaging agent. Uptake patterns of 111In-coNGR and 111In-co(NGR)4
      coincided with CD13 immunohistochemistry on excised hearts. Blood stability tests
      indicated better stability for both novel imaging agents after 50 min blood
      incubation compared to the disulfide-cyclized cNGR imaging agent. In mice, both
      coNGR peptides cleared rapidly from the blood mainly via the kidneys. In
      addition, co(NGR)4 showed a significantly higher specific uptake in infarcted
      myocardium compared to coNGR and thus is a promising sensitive imaging agent for
      detection of angiogenesis in infarcted myocardium.

PMID- 29204108
TI  - Cross-Dependency Inference in Multi-Layered Networks: A Collaborative Filtering
      Perspective.
AB  - The increasingly connected world has catalyzed the fusion of networks from
      different domains, which facilitates the emergence of a new network model-multi
      layered networks. Examples of such kind of network systems include critical
      infrastructure networks, biological systems, organization-level collaborations,
      cross-platform e-commerce, and so forth. One crucial structure that distances
      multi-layered network from other network models is its cross-layer dependency,
      which describes the associations between the nodes from different layers.
      Needless to say, the cross-layer dependency in the network plays an essential
      role in many data mining applications like system robustness analysis and complex
      network control. However, it remains a daunting task to know the exact dependency
      relationships due to noise, limited accessibility, and so forth. In this article,
      we tackle the cross-layer dependency inference problem by modeling it as a
      collective collaborative filtering problem. Based on this idea, we propose an
      effective algorithm Fascinate that can reveal unobserved dependencies with linear
      complexity. Moreover, we derive Fascinate-ZERO, an online variant of Fascinate
      that can respond to a newly added node timely by checking its neighborhood
      dependencies. We perform extensive evaluations on real datasets to substantiate
      the superiority of our proposed approaches.

PMID- 29204110
TI  - Corrigendum: beta2-Adrenergic Receptor-Mediated HIF-1alpha Upregulation Mediates
      Blood Brain Barrier Damage in Acute Cerebral Ischemia.
AB  - [This corrects the article on p. 257 in vol. 10, PMID: 28855859.].

PMID- 29204111
TI  - Stereological Study on the Positive Effect of Running Exercise on the Capillaries
      in the Hippocampus in a Depression Model.
AB  - Running exercise is an effective method to improve depressive symptoms when
      combined with drugs. However, the underlying mechanisms are not fully clear.
      Cerebral blood flow perfusion in depressed patients is significantly lower in the
      hippocampus. Physical activity can achieve cerebrovascular benefits. The purpose
      of this study was to evaluate the impacts of running exercise on capillaries in
      the hippocampal CA1 and dentate gyrus (DG) regions. The chronic unpredictable
      stress (CUS) depression model was used in this study. CUS rats were given 4 weeks
      of running exercise from the fifth week to the eighth week (20 min every day from
      Monday to Friday each week). The sucrose consumption test was used to measure
      anhedonia. Furthermore, stereological methods were used to investigate the
      capillary changes among the control group, CUS/Standard group and CUS/Running
      group. Sucrose consumption significantly increased in the CUS/Running group.
      Running exercise has positive effects on the capillaries parameters in the
      hippocampal CA1 and DG regions, such as the total volume, total length and total
      surface area. These results demonstrated that capillaries are protected by
      running exercise in the hippocampal CA1 and DG might be one of the structural
      bases for the exercise-induced treatment of depression-like behavior. These
      results suggest that drugs and behavior influence capillaries and may be
      considered as a new means for depression treatment in the future.

PMID- 29204112
TI  - Flexible Visuomotor Associations in Touchscreen Control.
AB  - To move real objects, our hand needs to get in direct physical contact with the
      object. However, this is not necessarily the case when interacting with virtual
      objects, for example when displacing objects on tablets by swipe movements. Here,
      we performed two experiments to study the behavioral strategies of these
      movements, examining how visual information about the virtual object is mapped
      into a swipe that moves the object into a goal location. In the first experiment,
      we investigated how swiping behavior depends on whether objects were located
      within or outside the swiping workspace. Results show that participants do not
      start the swipe movement by placing their finger on the virtual object, as they
      do when reaching to real objects, but rather keep a systematic distance between
      the object location and the initial swipe location. This mismatch, which was
      experimentally imposed by placing the object outside the workspace, also occurred
      when the object was within the workspace. In the second experiment, we
      investigated which factors determine this mismatch by systematically manipulating
      the initial hand location, the location of the object and the location of the
      goal. Dimensionality reduction of the data showed that three factors are taken
      into account when participants choose the initial swipe location: the expected
      total movement distance, the distance between their finger on the screen and the
      object, and a preference not to cover the object. The weight given to each factor
      differed among individuals. These results delineate, for the first time, the
      flexibility of visuomotor associations in the virtual world.

PMID- 29204109
TI  - Intracellular Cholesterol Trafficking and Impact in Neurodegeneration.
AB  - Cholesterol is a critical component of membrane bilayers where it plays key
      structural and functional roles by regulating the activity of diverse signaling
      platforms and pathways. Particularly enriched in brain, cholesterol homeostasis
      in this organ is singular with respect to other tissues and exhibits a
      heterogeneous regulation in distinct brain cell populations. Due to the key role
      of cholesterol in brain physiology and function, alterations in cholesterol
      homeostasis and levels have been linked to brain diseases and neurodegeneration.
      In the case of Alzheimer disease (AD), however, this association remains unclear
      with evidence indicating that either increased or decreased total brain
      cholesterol levels contribute to this major neurodegenerative disease. Here,
      rather than analyzing the role of total cholesterol levels in neurodegeneration,
      we focus on the contribution of intracellular cholesterol pools, particularly in
      endolysosomes and mitochondria through its trafficking via specialized membrane
      domains delineated by the contacts between endoplasmic reticulum and
      mitochondria, in the onset of prevalent neurodegenerative diseases such as AD,
      Parkinson disease, and Huntington disease as well as in lysosomal disorders like
      Niemann-Pick type C disease. We dissect molecular events associated with
      intracellular cholesterol accumulation, especially in mitochondria, an event that
      results in impaired mitochondrial antioxidant defense and function. A better
      understanding of the mechanisms involved in the distribution of cholesterol in
      intracellular compartments may shed light on the role of cholesterol homeostasis
      disruption in neurodegeneration and may pave the way for specific intervention
      opportunities.

PMID- 29204113
TI  - Effect of Electro-Acupuncture and Moxibustion on Brain Connectivity in Patients
      with Crohn's Disease: A Resting-State fMRI Study.
AB  - Acupuncture and moxibustion have been shown to be effective in treating Crohn's
      disease (CD), but their therapeutic mechanisms remain unclear. Here we compared
      brain responses to either electro-acupuncture or moxibustion treatment in CD
      patients experiencing remission. A total of 65 patients were randomly divided
      into an electro-acupuncture group (n = 32) or a moxibustion group (n = 33), and
      treated for 12 weeks. Eighteen patients in the electro-acupuncture group and 20
      patients in the moxibustion group underwent resting-state functional magnetic
      resonance imaging at baseline and after treatment. Seed-based analysis was used
      to compare the resting-state functional connectivity (rsFC) between bilateral
      hippocampus and other brain regions before and after the treatments, as well as
      between the two groups. The CD activity index (CDAI) and inflammatory bowel
      disease questionnaire (IBDQ) were used to evaluate disease severity and patient
      quality of life. Electro-acupuncture and moxibustion both significantly reduced
      CDAI values and increased IBDQ scores. In the electro-acupuncture group, the rsFC
      values between bilateral hippocampus and anterior middle cingulate cortex (MCC)
      and insula were significantly increased, and the changes were negatively
      correlated with the CDAI scores. In the moxibustion group, the rsFC values
      between bilateral hippocampus and precuneus as well as inferior parietal lobe
      (IPC) were significantly elevated, and the changes were negatively correlated
      with the CDAI scores. We conclude that the therapeutic effects of electro
      acupuncture and moxibustion on CD may involve the differently modulating brain
      homeostatic afferent processing network and default mode network (DMN),
      respectively.

PMID- 29204114
TI  - Vitality Forms Expressed by Others Modulate Our Own Motor Response: A Kinematic
      Study.
AB  - During social interaction, actions, and words may be expressed in different ways,
      for example, gently or rudely. A handshake can be gentle or vigorous and,
      similarly, tone of voice can be pleasant or rude. These aspects of social
      communication have been named vitality forms by Daniel Stern. Vitality forms
      represent how an action is performed and characterize all human interactions. In
      spite of their importance in social life, to date it is not clear whether the
      vitality forms expressed by the agent can influence the execution of a subsequent
      action performed by the receiver. To shed light on this matter, in the present
      study we carried out a kinematic study aiming to assess whether and how visual
      and auditory properties of vitality forms expressed by others influenced the
      motor response of participants. In particular, participants were presented with
      video-clips showing a male and a female actor performing a "giving request" (give
      me) or a "taking request" (take it) in visual, auditory, and mixed modalities
      (visual and auditory). Most importantly, requests were expressed with rude or
      gentle vitality forms. After the actor's request, participants performed a
      subsequent action. Results showed that vitality forms expressed by the actors
      influenced the kinematic parameters of the participants' actions regardless to
      the modality by which they are conveyed.

PMID- 29204116
TI  - P2Y12 Receptor Antagonist, Clopidogrel, Does Not Contribute to Risk of
      Osteoporotic Fractures in Stroke Patients.
AB  - Background: Stroke is a leading cause of mortality and morbidity. It is
      associated with excessive bone loss and risk of fracture in stroke patients is
      high. The P2Y12R antagonist and platelet inhibitor, clopidogrel, is widely used
      for secondary prevention after a stroke. However, recent studies have shown that
      clopidogrel has negative effects on bone and that long-term clopidogrel use is
      associated with increased fracture risk. The purpose of the current study was
      therefore to investigate the association of clopidogrel treatment with risk of
      fractures in stroke and TIA patients. Methods: The study was a cohort study
      including all subjects who were prescribed clopidogrel between 1996 and 2008 in
      Denmark (n = 77,503). Age- and gender matched controls (n = 232,510) were
      randomly selected from the background population. The study end-points were
      occurrence of stroke or TIA and occurrence of fracture. Clopidogrel use was
      primary exposure. Results: Ischemic stroke increased risk of fracture by 50%
      while haemorrhagic stroke and TIA increased the risk by 30%. However, after
      adjusting for multiple confounders only patients with ischemic stroke and
      haemorrhagic stroke had increased fracture risk. Clopidogrel use was not
      associated with increased fracture risk in subjects with ischaemic stroke or TIA.
      In contrast, after adjusting for multiple confounders clopidogrel treatment was
      associated with a 10-35% reduced risk of fracture. Conclusion: Patients with
      stroke have increased risk of osteoporotic fractures, but clopidogrel treatment
      does not increase fracture risk. In contrast, patients less adherent to the
      treatment have lower risk of fractures than non-users and patients with high
      adherence. However, based on the increased risk in stroke patients, clinicians
      should consider evaluation of bone status of these patients.

PMID- 29204115
TI  - A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in
      Indian School Children Receiving a Combination of Bacopa monnieri and
      Micronutrient Supplementation vs. Placebo.
AB  - Several studies have indicated a chronic cognitive enhancing effect of Bacopa
      monnieri across different ages and cognitive impairment associated with vitamin
      and mineral deficiencies in children. Therefore, we investigated the effects of 4
      month supplementation with a combination of B. monnieri extract and multiple
      micronutrients on cognitive functions in Indian school children aged 7-12 years.
      This was a randomized, double-blind, parallel design, single-center study in
      which 300 children were randomized to receive a beverage either fortified with B.
      monnieri and multiple micronutrients ("fortified") or a non-fortified isocaloric
      equivalent ("control") twice-daily for 4 months. Cognitive function was assessed
      by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered
      at baseline, Day 60 and Day 121. The primary endpoint was change in short-term
      memory (working memory) from baseline in subjects receiving "fortified" vs.
      "control" beverages after 4 months. Secondary endpoints included sustained
      attention, episodic memory, and executive function. The "fortified" beverage did
      not significantly improve short-term memory or any of the secondary outcomes
      tested relative to the "control" beverage. However, the spatial working memory
      "strategy" score showed significant improvement on Day 60 (difference between
      groups in change from baseline: -0.55; p < 0.05), but not on Day 121 due to the
      active intervention. Study products were well-tolerated. Reasons for these
      unexpected findings are discussed.

PMID- 29204117
TI  - Protective Effect of Pogostone on 2,4,6-Trinitrobenzenesulfonic Acid-Induced
      Experimental Colitis via Inhibition of T Helper Cell.
AB  - Inflammatory bowel disease (IBD) is a chronic immune-related disease mainly
      caused by the disequilibrium of T helper (Th) cell paradigm? Pogostone (PO) is
      one of the major chemical constituents of Pogostemon cablin (Blanco) Benth. The
      present study aims to investigate the potential benefit of PO against IBD in a
      2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis model. PO
      treatment by enema significantly brought down the disease activity index (DAI) of
      the TNBS-challenged rats, which was manifested by the ameliorated inflammatory
      features including ulceration, adhesion, and edema. Hematoxylin-eosin (HE)
      staining and immunohistochemistry analysis showed that PO effectively relived
      colon damage by restoring epithelium, and more importantly, by inhibiting the
      infiltration of pro-inflammatory Th1 and Th17 cells in the colon. Additionally,
      PO inhibited the activity of myeloperoxidase and secretion of inflammatory
      cytokines including IFN-gamma, IL-12p70, IL-17A, and IL-10. Together with our
      previous findings, the present data indicated that the anti-IBD effect of PO
      probably related to its direct inhibition on Th cell proliferation and
      suppression of the cytokines secretion. These results highlighted the potential
      of PO as a promising candidate to relieve IBD.

PMID- 29204118
TI  - The Sources of Chemical Contaminants in Food and Their Health Implications.
AB  - Food contamination is a matter of serious concern, as the high concentration of
      chemicals present in the edibles poses serious health risks. Protecting the
      public from the degrees of the harmfulness of contaminated foods has become a
      daunting task. This article highlights the causes, types, and health implications
      of chemical contamination in food. The food contamination could be due to
      naturally occurring contaminants in the environment or artificially introduced by
      the human. The phases of food processing, packaging, transportation, and storage
      are also significant contributors to food contamination. The implications of
      these chemical contaminants on human health are grave, ranging from mild
      gastroenteritis to fatal cases of hepatic, renal, and neurological syndromes.
      Although, the government regulates such chemicals in the eatables by prescribing
      minimum limits that are safe for human consumption yet measures still need to be
      taken to curb food contamination entirely. Therefore, a variety of food needs to
      be inspected and measured for the presence of chemical contaminants. The
      preventative measures pertaining about the food contaminants problems are pointed
      out and discussed.

PMID- 29204119
TI  - Differential Effects of Inactivation of Discrete Regions of Medial Prefrontal
      Cortex on Memory Consolidation of Moderate and Intense Inhibitory Avoidance
      Training.
AB  - It has been found that the medial prefrontal cortex (mPFC) is involved in memory
      encoding of aversive events, such as inhibitory avoidance (IA) training.
      Dissociable roles have been described for different mPFC subregions regarding
      various memory processes, wherein the anterior cingulate cortex (ACC), prelimbic
      cortex (PL), and infralimbic cortex (IL) are involved in acquisition, retrieval,
      and extinction of aversive events, respectively. On the other hand, it has been
      demonstrated that intense training impedes the effects on memory of treatments
      that typically interfere with memory consolidation. The aim of this work was to
      determine if there are differential effects on memory induced by reversible
      inactivation of neural activity of ACC, PL, or IL produced by tetrodotoxin (TTX)
      in rats trained in IA using moderate (1.0 mA) and intense (3.0 mA) foot-shocks.
      We found that inactivation of ACC has no effects on memory consolidation,
      regardless of intensity of training. PL inactivation impairs memory consolidation
      in the 1.0 mA group, while no effect on consolidation was produced in the 3.0 mA
      group. In the case of IL, a remarkable amnestic effect in LTM was observed in
      both training conditions. However, state-dependency can explain the amnestic
      effect of TTX found in the 3.0 mA IL group. In order to circumvent this effect,
      TTX was injected into IL immediately after training (thus avoiding state
      dependency). The behavioral results are equivalent to those found after PL
      inactivation. Therefore, these findings provide evidence that PL and IL, but not
      ACC, mediate LTM of IA only in moderate training.

PMID- 29204120
TI  - Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis.
AB  - One-third of the world's population has been infected with Mycobacterium
      tuberculosis (M. tuberculosis), a primary pathogen of the mammalian respiratory
      system, while about 10% of latent infections progress to active tuberculosis
      (TB), indicating that host and environmental factors may determine the outcomes
      such as infection clearance/persistence and treatment prognosis. The gut
      microbiota is essential for development of host immunity, defense, nutrition and
      metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M.
      tuberculosis infection and prognosis. In current study we characterized the
      differences in gut bacterial communities in new tuberculosis patients (NTB),
      recurrent tuberculosis patients (RTB), and healthy control. The abundance-based
      coverage estimator (ACE) showed the diversity index of the gut microbiota in the
      patients with recurrent tuberculosis was increased significantly compared with
      healthy controls (p < 0.05). At the phyla level, Actinobacteria and
      Proteobacteria, which contain many pathogenic species, were significantly
      enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing
      a variety of beneficial commensal organisms, was reduced in the patients with the
      recurrent tuberculosis compared to healthy controls. The Gram-negative genus
      Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from
      phylum of Firmicutes were significantly decreased in both the new and recurrent
      TB patient groups, compared with the healthy control group (p < 0.05). We also
      found that there was a positive correlation between the gut microbiota and
      peripheral CD4+ T cell counts in the patients. This study, for the first time,
      showed associations between gut microbiota with tuberculosis and its clinical
      outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be
      beneficial for host recovery and prevention of recurrence of M. tuberculosis
      infection.

PMID- 29204121
TI  - Abnormal CFTR Affects Glucagon Production by Islet alpha Cells in Cystic Fibrosis
      and Polycystic Ovarian Syndrome.
AB  - Glucagon, produced by islet alpha cells, functions to increase blood glucose.
      Abnormal glucose levels are often seen in cystic fibrosis (CF), a systematic
      disease caused by mutations of the CF transmembrane conductance regulator (CFTR),
      and in polycystic ovarian syndrome (PCOS), an endocrine disorder featured with
      hyperandrogenism affecting 5-10% women of reproductive age. Here, we explored the
      role of CFTR in glucagon production in alpha cells and its possible contribution
      to glucagon disturbance in CF and PCOS. We found elevated fasting glucagon levels
      in CFTR mutant (DF508) mice compared to the wildtypes. Glucagon and prohormone
      convertase 2 (PC2) were also upregulated in CFTR inhibitor-treated or DF508
      islets, as compared to the controls or wildtypes, respectively.
      Dihydrotestosterone (DHT)-induced PCOS rats exhibited significantly lower fasting
      glucagon levels with higher CFTR expression in alpha cells compared to that of
      controls. Treatment of mouse islets or alphaTC1-9 cells with DHT enhanced CFTR
      expression and reduced the levels of glucagon and PC2. The inhibitory effect of
      DHT on glucagon production was blocked by CFTR inhibitors in mouse islets, and
      mimicked by overexpressing CFTR in alphaTC1-9 cells with reduced phosphorylation
      of the cAMP/Ca2+ response element binding protein (p-CREB), a key transcription
      factor for glucagon and PC2. These results revealed a previously undefined role
      of CFTR in suppressing glucagon production in alpha-cells, defects in which may
      contribute to glucose metabolic disorder seen in CF and PCOS.

PMID- 29204122
TI  - LETM1-Mediated K+ and Na+ Homeostasis Regulates Mitochondrial Ca2+ Efflux.
AB  - Ca2+ transport across the inner membrane of mitochondria (IMM) is of major
      importance for their functions in bioenergetics, cell death and signaling. It is
      therefore tightly regulated. It has been recently proposed that LETM1-an IMM
      protein with a crucial role in mitochondrial K+/H+ exchange and volume
      homeostasis-also acts as a Ca2+/H+ exchanger. Here we show for the first time
      that lowering LETM1 gene expression by shRNA hampers mitochondrial K+/H+ and
      Na+/H+ exchange. Decreased exchange activity resulted in matrix K+ accumulation
      in these mitochondria. Furthermore, LETM1 depletion selectively decreased
      Na+/Ca2+ exchange mediated by NCLX, as observed in the presence of ruthenium red,
      a blocker of the Mitochondrial Ca2+ Uniporter (MCU). These data confirm a key
      role of LETM1 in monovalent cation homeostasis, and suggest that the effects of
      its modulation on mitochondrial transmembrane Ca2+ fluxes may reflect those on
      Na+/H+ exchange activity.

PMID- 29204123
TI  - Network Modularity in Breast Cancer Molecular Subtypes.
AB  - Breast cancer is a heterogeneous and complex disease, a clear manifestation of
      this is its classification into different molecular subtypes. On the other hand,
      gene transcriptional networks may exhibit different modular structures that can
      be related to known biological processes. Thus, modular structures in
      transcriptional networks may be seen as manifestations of regulatory structures
      that tightly controls biological processes. In this work, we identify modular
      structures on gene transcriptional networks previously inferred from microarray
      data of molecular subtypes of breast cancer: luminal A, luminal B, basal, and
      HER2-enriched. We analyzed the modules (communities) found in each network to
      identify particular biological functions (described in the Gene Ontology
      database) associated to them. We further explored these modules and their
      associated functions to identify common and unique features that could allow a
      better level of description of breast cancer, particularly in the basal-like
      subtype, the most aggressive and poor prognosis manifestation. Our findings
      related to the immune system and a decrease in cell death-related processes in
      basal subtype could help to understand it and design strategies for its
      treatment.

PMID- 29204124
TI  - Alternative Splicing of NOX4 in the Failing Human Heart.
AB  - Increased oxidative stress is a major contributor to the development and
      progression of heart failure, however, our knowledge on the role of the distinct
      NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore,
      we aimed to characterize NOX4 expression in human samples from healthy and
      failing hearts. Explanted human heart samples (left and right ventricular, and
      septal regions) were obtained from patients suffering from heart failure of
      ischemic or dilated origin. Control samples were obtained from donor hearts that
      were not used for transplantation. Deep RNA sequencing of the cardiac
      transcriptome indicated extensive alternative splicing of the NOX4 gene in heart
      failure as compared to samples from healthy donor hearts. Long distance PCR
      analysis with a universal 5'-3' end primer pair, allowing amplification of
      different splice variants, confirmed the presence of the splice variants. To
      assess translation of the alternatively spliced transcripts we determined protein
      expression of NOX4 by using a specific antibody recognizing a conserved region in
      all variants. Western blot analysis showed up-regulation of the full-length NOX4
      in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms
      both in control and failing samples with disease-associated expression pattern.
      We describe here for the first time that NOX4 undergoes extensive alternative
      splicing in human hearts which gives rise to the expression of different enzyme
      isoforms. The full length NOX4 is significantly upregulated in ischemic
      cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure.

PMID- 29204125
TI  - Alcohol's Effects on Pair-Bond Maintenance in Male Prairie Voles.
AB  - Alcohol abuse can have devastating effects on social relationships. In
      particular, discrepant patterns of heavy alcohol consumption are associated with
      increased rates of separation and divorce. Previous studies have attempted to
      model these effects of alcohol using socially monogamous prairie voles. These
      studies showed that alcohol consumption can inhibit the formation of pair bonds
      in this species. While these findings indicated that alcohol's effects on social
      attachments can involve biological mechanisms, the formation of pair bonds does
      not properly model long-term human attachments. To overcome this caveat, this
      study explored whether discordant or concordant alcohol consumption between
      individuals within established pairs affects maintenance of pair bonds in male
      prairie voles. Male and female prairie voles were allowed to form a pair bond for
      1 week. Following this 1-week cohabitation period, males received access to 10%
      continuous ethanol; meanwhile, their female partners had access to either alcohol
      and water or just water. When there was a discrepancy in alcohol consumption,
      male prairie voles showed a decrease in partner preference (PP). Conversely, when
      concordant drinking occurred, males showed no inhibition in PP. Further analysis
      revealed a decrease in oxytocin immunoreactivity in the paraventricular nucleus
      of alcohol-exposed males that was independent of the drinking status of their
      female partners. On the other hand, only discordant alcohol consumption resulted
      in an increase of FosB immunoreactivity in the periaqueductal gray of male voles,
      a finding suggesting a potential involvement of this brain region in the effects
      of alcohol on maintenance of pair bonds. Our studies provide the first evidence
      that alcohol has effects on established pair bonds and that partner drinking
      status plays a large role in these effects.

PMID- 29204126
TI  - Pharmacokinetic, Ambulatory, and Hyperthermic Effects of 3,4-Methylenedioxy-N
      Methylcathinone (Methylone) in Rats.
AB  - Methylone (3,4-methylenedioxy-N-methylcathinone) is a synthetic cathinone analog
      of the recreational drug ecstasy. Although it is marketed to recreational users
      as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi
      organ system failure have been reported. Since psychopharmacological data remain
      scarce, we have focused our research on pharmacokinetics, and on a detailed
      evaluation of temporal effects of methylone and its metabolite nor-methylone on
      behavior and body temperature in rats. Methylone [5, 10, 20, and 40 mg/kg
      subcutaneously (s.c.)] and nor-methylone (10 mg/kg s.c.) were used in adolescent
      male Wistar rats across three behavioral/physiological procedures and in two
      temporal windows from administration (15 and 60 min) in order to test: locomotor
      effects in the open field, sensorimotor gating in the test of prepulse inhibition
      (PPI), and effects on rectal temperature in individually and group-housed rats.
      Serum and brain pharmacokinetics after 10 mg/kg s.c. over 8 h were analyzed using
      liquid chromatography mass spectrometry. Serum and brain levels of methylone and
      nor-methylone peaked at 30 min after administration, both drugs readily
      penetrated the brain with serum: brain ratio 1:7.97. Methylone dose-dependently
      increased overall locomotion. It also decrease the amount of time spent in the
      center of open field arena in dose 20 mg/kg and additionally this dose induced
      stereotyped circling around the arena walls. The maximum of effects corresponded
      to the peak of its brain concentrations. Nor-methylone had approximately the same
      behavioral potency. Methylone also has weak potency to disturb PPI. Behavioral
      testing was not performed with 40 mg/kg, because it was surprisingly lethal to
      some animals. Methylone 10 and 20 mg/kg s.c. induced hyperthermic reaction which
      was more pronounced in group-housed condition relative to individually housed
      rats. To conclude, methylone increased exploration and/or decreased anxiety in
      the open field arena and with nor-methylone had short duration of action with
      effects typical for mixed indirect dopamine-serotonin agonists such as 3,4
      metyhlenedioxymethamphetamine (MDMA) or amphetamine. Given the fact that the
      toxicity was even higher than the known for MDMA and that it can cause
      hyperthermia it possess a threat to users with the risk for serotonin syndrome
      especially when used in crowded conditions.

PMID- 29204127
TI  - Synthetic Aminoindanes: A Summary of Existing Knowledge.
AB  - Objectives: Aminoindanes ("bath salts," a class of novel psychoactive substances,
      NPSs) increased rapidly in popularity on the recreational drug market,
      particularly after mephedrone and other synthetic cathinones were banned in the
      UK in 2010. Novel aminoindanes continue to emerge, but relatively little is known
      about their effects and risks. Their history, chemistry, pharmacology, behavioral
      effects, pharmacokinetics, and toxicity are reviewed in this paper. Methods:
      Scientific literature was searched on ISI Web of Knowledge: Web of Science (WoS)
      during June and July 2017, using English language terms: aminoindanes such as 5,6
      methylenedioxy-2-aminoindane (MDAI), 5-iodo-2-aminoindane (5-IAI), 2-aminoindane
      (2-AI), 5,6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), and 5-methoxy-6-methyl
      2-aminoindane (MMAI). WoS was selected as it searches several databases
      simultaneously and has quality criteria for inclusion. For typical use and
      effects, Erowid, PsychonautWiki, Bluelight, and Drugs-Forum were searched; for
      legal status and epidemiology, the European Information System and Database on
      New Drugs (EDND) was used. Results: Aminoindanes were first synthesized for
      medical use, e.g., as anti-Parkinsonian drugs and later as a potential compound
      facilitating psychotherapy; however, they are now widely substituted for ecstasy.
      Their mechanisms of action (primarily via serotonin) mean that they may pose a
      significant risk of serotonin syndrome at high doses or when combined with other
      drugs. Fatally toxic effects have been observed both in the laboratory in animal
      studies and in clinic, where deaths related with aminoindanes have been reported.
      Conclusion: Greater knowledge about aminoindanes is urgently required to decrease
      risks of fatal intoxication, and appropriate legislation is needed to protect
      public health without impeding research.

PMID- 29204128
TI  - The Art Gallery Test: A Preliminary Comparison between Traditional
      Neuropsychological and Ecological VR-Based Tests.
AB  - Ecological validity should be the cornerstone of any assessment of cognitive
      functioning. For this purpose, we have developed a preliminary study to test the
      Art Gallery Test (AGT) as an alternative to traditional neuropsychological
      testing. The AGT involves three visual search subtests displayed in a virtual
      reality (VR) art gallery, designed to assess visual attention within an
      ecologically valid setting. To evaluate the relation between AGT and standard
      neuropsychological assessment scales, data were collected on a normative sample
      of healthy adults (n = 30). The measures consisted of concurrent paper-and-pencil
      neuropsychological measures [Montreal Cognitive Assessment (MoCA), Frontal
      Assessment Battery (FAB), and Color Trails Test (CTT)] along with the outcomes
      from the three subtests of the AGT. The results showed significant correlations
      between the AGT subtests describing different visual search exercises strategies
      with global and specific cognitive measures. Comparative visual search was
      associated with attention and cognitive flexibility (CTT); whereas visual
      searches involving pictograms correlated with global cognitive function (MoCA).

PMID- 29204129
TI  - "Maybe I Will Just Send a Quick Text..." - An Examination of Drivers'
      Distractions, Causes, and Potential Interventions.
AB  - Many people use cars all over the world. This is, however, not done without risk,
      as traffic accidents are one of the most common causes of death for adolescents
      worldwide. The number of deaths has steadily decreased, both worldwide and in
      Norway. Many of these accidents involve passenger cars and distracted driving.
      While there are many campaigns to improve safety in traffic, little research has
      looked at distractions. A recent report has investigated the occurrence of and
      damage caused by distraction, and one article has looked at what predicts
      baseline differences in levels of distracted driving. However, no one has tested
      an intervention to decrease distracted behavior in traffic. Motivational
      variables suggested by the Theory of Planned Behavior, personality traits, and
      demographic variables show utility in similar contexts and are all tested in this
      project. Data from two samples were collected to investigate the nature of
      distractions in traffic, what factors predict baseline levels of distractions,
      and to test an intervention to reduce distractions. Both samples feature randomly
      assigned intervention and control groups. The first sample (n = 1100 total; n =
      208 was licensed to drive) consisted of high school students from all over Norway
      as a part of a larger attitudinal campaign, while the second sample (n = 414) was
      more general. The second tested a digital version of implementation intentions
      designed as volitional help sheets. The results from both samples suggest that
      there are some robust differences between people in how much they are distracted
      in everyday life, while some variables need further research. The second study
      failed to uncover any effects of the intervention. Reasons for this are
      discussed, along with points on the efficacy of digital interventions, the design
      of the volitional help sheets, and the design of the study in general.
      Notwithstanding the ineffectual interventions, this study contains novel
      information about baseline differences in distractive behavior that may further
      impact future behavior change interventions and guide future research.

PMID- 29204130
TI  - Development of Attention to Faces during the First 3 Years: Influences of
      Stimulus Type.
AB  - The development of attention toward faces was explored during the first 3 years
      of life in 54 children aged between 3 and 36 months. In contrast to previous
      research, attention to faces was assessed using both static images and a dynamic
      video sequence in the same participants. Separate analyses at each age and
      exploratory longitudinal analyses indicate a preference for faces during the
      first year, followed by a decline during the second year. These results suggest
      that attention to faces does not follow a linear increasing pattern over
      development, and that social attention patterns are influenced by stimulus
      characteristics.

PMID- 29204131
TI  - 'Leave Your Ego at the Door': A Narrative Investigation into Effective Wingsuit
      Flying.
AB  - In recent years there has been a rapid growth in interest in extreme sports. For
      the most part research has focused on understanding motivations for participation
      in extreme sports and very little research has attempted to investigate the
      psychological structure of effective performance. Those few studies that have
      attempted to explore this issue have tested models designed for traditional sport
      on adventure sports. However, extreme sports are not the same as adventure sports
      or traditional sports. This study employed a narrative approach to investigate
      experiences of effective performance in the extreme sport of proximity wingsuit
      flying. An overarching theme we labeled 'leave your ego at the door,' emerged
      based on four sub-themes: (1) know thy self, (2) know thy skills, (3) know the
      environment now, and (4) tame the 'inner animal.' These themes are presented and
      discussed in relation to performance and discovery narratives identified within
      elite sport, thereby shedding light on how participants' experiences of the
      extreme sport of proximity wingsuit flying differ from dominant stories within
      traditional sports.

PMID- 29204132
TI  - The Relationship between Regional Gray Matter Volume of Social Exclusion Regions
      and Personal Self-Esteem Is Moderated by Collective Self-Esteem.
AB  - According to sociometer theory, self-esteem is an internal monitor of positive
      social bonds to others. Social exclusion can break or threaten social bonds,
      which might be reflected by the brain structure of social exclusion regions.
      Thus, self-esteem might be influenced by structurally individual differences in
      these regions. It has been suggested that self-esteem can be divided into
      personal (PSE) and collective (CSE) self-esteem and CSE can bring individuals
      many benefits, such as acceptance, belonging, and social support, which could
      further maintain or increase their PSE. Based on this, we hypothesized that CSE
      might moderate the relationship between structurally individual differences in
      social exclusion regions and PSE. Therefore, in the present study, the moderating
      effect of CSE on the relationships between PSE and individual differences in
      regional gray matter volume (rGMV) of 10 social exclusion regions from previous
      meta-analysis of social exclusion were investigated using voxel-based
      morphometry. The results showed that CSE played a moderating role in the
      relationship between PSE and rGMV of the left posterior cingulate cortex (PCC).
      Specifically, PSE was positively associated with rGMV of left PCC in lower CSE,
      while there was no significant relationship between PSE and rGMV of left PCC in
      higher CSE. Therefore, we believe that compared with a higher CSE, because of
      lack of acceptance, belonging, and social support from valued groups, lower CSE
      individuals might be more prone to be influenced by social exclusion with
      decreased rGMV of the left PCC, which makes them more prone to develop lower PSE.

PMID- 29204133
TI  - Gratitude in Organizations: A Contribution for Healthy Organizational Contexts.
AB  - This article reviews the construct of gratitude. Gratitude has been shown to be a
      fundamental resource for strengthening individual well-being. From a positive
      psychology perspective, gratitude is recognized as a promising opportunity for
      individuals because it can be enhanced through specific training according to a
      primary prevention framework. In organizations, gratitude is now thought to be
      crucial to employees' efficiency, success, and productivity while also improving
      organizational citizenship behaviors, prosocial organizational behavior, and the
      organizational climate. Thus, gratitude is noteworthy because it increases
      positive relationships, social support, and workers' well-being, reduces negative
      emotions at the workplace, and enhances organizational health and success. This
      perspective article concludes by suggesting new directions for gratitude research
      and intervention in the organizational context.

PMID- 29204134
TI  - Retraction: How Traumatic Violence Permanently Changes Shopping Behavior.
AB  - [This retracts the article on p. 1298 in vol. 7, PMID: 27656152.].

PMID- 29204135
TI  - Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle
      Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.
AB  - Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves
      muscle glucose uptake in rodents. However, whether ucOC can directly increase
      glucose uptake in both glycolytic and oxidative muscles and the possible
      mechanisms of action still need further exploration. We tested the hypothesis
      that ucOC per se stimulates muscle glucose uptake via extracellular signal
      regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK),
      and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B
      (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade. Extensor digitorum
      longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided
      into halves, and then incubated with ucOC with or without the pretreatment of ERK
      inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It
      also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both
      muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had
      no significant effect on the phosphorylation of AMPKalpha (Thr172). The
      inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC
      stimulated glucose uptake and AS160 phosphorylation in both muscle types, but
      appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken
      together, ucOC at the physiological range directly increased glucose uptake in
      both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC
      effect on muscle glucose uptake seem to be muscle type-specific, involving
      enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation.
      Our study suggests that, since ucOC increases muscle glucose uptake without
      insulin, it could be considered as a potential agent to improve muscle glucose
      uptake in insulin resistant conditions.

PMID- 29204138
TI  - Retraction: Pseudopyronine B: A Potent Antimicrobial and Anticancer Molecule
      Isolated from a Pseudomonas mosselii.
AB  - [This retracts the article on p. 1307 in vol. 7, PMID: 27617005.].

PMID- 29204136
TI  - Suppression of Poxvirus Replication by Resveratrol.
AB  - Poxviruses continue to cause serious diseases even after eradication of the
      historically deadly infectious human disease, smallpox. Poxviruses are currently
      being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is
      a natural polyphenol stilbenoid found in plants that has been shown to inhibit or
      enhance replication of a number of viruses, but the effect of resveratrol on
      poxvirus replication is unknown. In the present study, we found that resveratrol
      dramatically suppressed the replication of vaccinia virus (VACV), the prototypic
      member of poxviruses, in various cell types. Resveratrol also significantly
      reduced the replication of monkeypox virus, a zoonotic virus that is endemic in
      Western and Central Africa and causes human mortality. The inhibitory effect of
      resveratrol on poxviruses is independent of VACV N1 protein, a potential
      resveratrol binding target. Further experiments demonstrated that resveratrol had
      little effect on VACV early gene expression, while it suppressed VACV DNA
      synthesis, and subsequently post-replicative gene expression.

PMID- 29204137
TI  - Microbial Mechanistic Insight into the Role of Inulin in Improving Maternal
      Health in a Pregnant Sow Model.
AB  - General consumption of "western diet" characterized by high refined
      carbohydrates, fat and energy intake has resulted in a global obesity epidemics
      and related metabolic disturbance even for pregnant women. Pregnancy process is
      accompanied by substantial hormonal, metabolic and immunological changes during
      which gut microbiota is also remarkably remodeled. Dietary fiber has been
      demonstrated to have a striking role in shifting the microbial composition so as
      to improve host metabolism and health in non-pregnant individuals. The present
      study was conducted to investigate effects of adding a soluble dietary fiber
      inulin (0 or 1.5%) to low- or high- fat (0 or 5% fat addition) gestational diet
      on maternal and neonatal health and fecal microbial composition in a sow model.
      Results showed that inulin addition decreased the gestational body weight gain
      and fat accumulation induced by fat addition. Circulating concentrations of pro
      inflammatory cytokine IL-6, adipokine leptin and chemerin were decreased by
      inulin supplementation. Inulin addition remarkably reduced the average BMI of
      newborn piglets and the within litter BMI distributions (%) ranging between 17
      and 20 kg/m2, and increased the BMI distribution ranging between 14 and 17 kg/m2.
      16S rRNA gene sequencing of the V3-V4 region showed that fecal microbial changes
      at different taxonomic levels triggered by inulin addition predisposed the
      pregnant sow to be thinner and lower inflammatory. Meanwhile, fecal microbial
      composition was also profoundly altered by gestation stage with distinct changes
      occurring at perinatal period. Most representative volatile fatty acid (VFA)
      producing-related genera changed dramatically when reaching the perinatal period
      and varied degrees of increases were detected with inulin addition. Fecal VFA
      concentrations failed to show any significant effect with dietary intervention,
      however, were markedly increased at perinatal period. Our findings indicate that
      positive microbial changes resulted by 1.5% soluble fiber inulin addition would
      possibly be the potential mechanisms under which maternal body weight, metabolic
      and inflammatory status and neonatal BMI were improved. Besides, distinct changes
      of microbial community at perinatal period indicated the mother sow is undergoing
      a catabolic state with increased energy loss and inflammation response at that
      period compared with other stages of gestation.

PMID- 29204139
TI  - Mycobacterium tuberculosis Latent Antigen Rv2029c from the Multistage DNA Vaccine
      A39 Drives TH1 Responses via TLR-mediated Macrophage Activation.
AB  - Targeting of Mycobacterium tuberculosis (MTB) latent antigens comprises a crucial
      strategy for the development of alternative tuberculosis (TB) vaccine(s) that
      protects against TB reactivation. Here, we generated a multistage DNA vaccine,
      A39, containing the early antigens Ag85A and Rv3425 as well as the latency
      associated protein Rv2029c, which conferred protective immunity in a pre-exposure
      mouse model. Moreover, administration of the A39 vaccination after MTB exposure
      inhibited reactivation and resulted in significantly lower bacterial loads in the
      lungs and spleen of mice, compared to those in the control population.
      Subsequently, we investigated the effect of Rv2029c on innate immunity and
      characterized the molecular details of the interaction of this protein with the
      host via iTRAQ proteomic and biochemical assay analyses. Rv2029c activated
      macrophages, triggered the production of pro-inflammatory cytokines, and promoted
      toll-like receptor/mitogen-activated protein kinase (TLR/MAPK)-dependent
      macrophage apoptosis. Furthermore, Rv2029c treatment enhanced the ability of
      Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-infected macrophages to
      present antigens to CD4+ T cells in vitro, which correlated with an increase in
      MHC-II expression. Lastly, Rv2029c-treated macrophages activated T cells,
      effectively polarized CD4+ and CD8+ T cells to secrete IFN-gamma and IL-2, and
      specifically expanded a population of CD44highCD62LlowCD4+/CD8+ effector/memory
      cells, indicating that Rv2029c, as a specific recall antigen, contributes to Th1
      polarization in T cell immunity. These results suggest that Rv2029c and A39
      comprise promising targets for the development of next-generation clinical TB
      therapeutic vaccines.

PMID- 29204140
TI  - Comparative Outer Membrane Protein Analysis of High and Low-Invasive Strains of
      Cronobacter malonaticus.
AB  - Cronobacter are an important group of foodborne pathogens that has been linked to
      life-threatening infections in both infants and adults. The major infections
      associated with Cronobacter species are neonatal meningitis, necrotizing
      enterocolitis, and septicaemia. There are seven species in the Cronobacter genus,
      of which only three are of clinical importance; Cronobacter sakazakii,
      Cronobacter malonaticus, and Cronobacter turicensis. To date most studies have
      focussed on C. sakazakii as it is the major species associated with neonatal
      infections. However, recently C. malonaticus, in particular sequence type 7
      (ST7), has been noted as being prevalent in adult infections and therefore
      warranting further investigation. In this study, eight strains of C. malonaticus
      ST7, that had been isolated from a wide range of sources and varied in their in
      vitro virulence, were chosen for proteomic analysis of their outer membrane
      proteins (OMPs). One-dimensional gel analysis revealed a ~29 kDa size band that
      was only present in the highly invasive strains. Subsequent mass spectrometric
      analysis identified several peptides that matched the flagellin protein. The
      presence of flagellin protein was confirmed in 2D gel spot. Mass spectrometry
      analysis of total OMPs revealed that the four highly invasive C. malonaticus
      strains expressed the main flagellum proteins that were absent from the four low
      invasive strains. These were the flagellar hook protein FlgE, flagellar hook
      associated protein 1, flagellar hook-associated protein, flagellin, and flagellar
      hook-filament junction protein FlgL. This data indicates that C. malonaticus
      flagellar proteins may have an important role in the organism's invasion
      properties.

PMID- 29204141
TI  - Flos Lonicera Combined with Metformin Ameliorates Hepatosteatosis and Glucose
      Intolerance in Association with Gut Microbiota Modulation.
AB  - The gut microbiota is important in energy contribution, metabolism and immune
      modulation, and compositional disruption of the gut microbiota population is
      closely associated with chronic metabolic diseases like type 2 diabetes (T2D) and
      non-alcoholic fatty liver disease (NAFLD). Metformin (MET) and Flos Lonicera (FL)
      are common treatments for metabolic diseases in Western and Oriental medicinal
      fields. We evaluated the effect of treatment with FL and MET in combination on
      hepatosteatosis, glucose tolerance, and gut microbial composition. FL and MET
      were administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal
      model of genetic T2D and NAFLD. The FL+MET treatment reduced liver weight, serum
      cholesterol, insulin resistance, and hepatic MDA level and modulated the gut
      microbial composition. More specifically, the genera of Prevotella and
      Lactobacillus were negatively associated with the body and liver weights, hepatic
      TG and TC content, and serum insulin level. However, the relative abundance of
      these genera decreased in response to the FL+MET treatment. Interestingly,
      pathway prediction data revealed that the FL+MET treatment attenuated
      lipopolysaccharide-related pathways, in keeping with the decrease in serum and
      fecal endotoxin levels. FL and MET in combination exerts a synergistic effect on
      the improvement of hepatosteatosis and insulin sensitivity in OLETF rats, and
      modulates gut microbiota in association with the effect.

PMID- 29204142
TI  - Quantitative Detection of Active Vibrios Associated with White Plague Disease in
      Mussismilia braziliensis Corals.
AB  - Over recent decades several coral diseases have been reported as a significant
      threat to coral reef ecosystems causing the decline of corals cover and diversity
      around the world. The development of techniques that improve the ability to
      detect and quantify microbial agents involved in coral disease will aid in the
      elucidation of disease cause, facilitating coral disease detection and diagnosis,
      identification and pathogen monitoring, pathogen sources, vectors, and
      reservoirs. The genus Vibrio is known to harbor pathogenic strains to marine
      organisms. One of the best-characterized coral pathogens is Vibrio
      coralliilyticus, an aetilogic agent of White Plague Disease (WPD). We used
      Mussismilia coral tissue (healthy and diseased specimens) to develop a rapid
      reproducible detection system for vibrios based on RT-QPCR and SYBR chemistry. We
      were able to detect total vibrios in expressed RNA targeting the 16S rRNA gene at
      5.23 * 106 copies/MUg RNA and V. coralliilyticus targeting the pyrH gene at 5.10
      * 103 copies/MUg RNA in coral tissue. Detection of V. coralliilyticus in diseased
      and in healthy samples suggests that WPD in the Abrolhos Bank may be caused by a
      consortium of microorganism and not only a single pathogen. We developed a more
      practical and economic system compared with probe uses for the real-time
      detection and quantification of vibrios from coral tissues by using the 16S rRNA
      and pyrH gene. This qPCR assay is a reliable tool for the monitoring of coral
      pathogens, and can be useful to prevent, control, or reduce impacts in this
      ecosystem.

PMID- 29204143
TI  - Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation
      Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J
      Recombination.
AB  - V(D)J recombination is essential for the generation of diverse antigen receptor
      (AgR) repertoires. In B cells, immunoglobulin kappa (Igkappa) light chain
      recombination follows immunoglobulin heavy chain (Igh) recombination. We recently
      developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and
      DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed
      that two chromatin states at the recombination signal sequence (RSS) of VH genes
      are highly predictive of recombination in mouse pro-B cells. It is unknown
      whether local chromatin states contribute to Vkappa gene choice during Igkappa
      recombination. Here we adapt VDJ-seq to profile the Igkappa VkappaJkappa
      repertoire and present a comprehensive readout in mouse pre-B cells, revealing
      highly variable Vkappa gene usage. Integration with genome-wide datasets for
      histone modifications, DNase hypersensitivity, transcription factor binding and
      germline transcription identified PU.1 binding at the RSS, which was unimportant
      for Igh, as highly predictive of whether a Vkappa gene will recombine or not,
      suggesting that it plays a binary, all-or-nothing role, priming genes for
      recombination. Thereafter, the frequency with which these genes recombine was
      shaped both by the presence and level of enrichment of several other chromatin
      features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to
      the Igh locus, the chromatin landscape of the promoter, as well as of the RSS,
      contributes to Vkappa gene recombination. Thus, multiple facets of local
      chromatin features explain much of the variation in Vkappa gene usage. Together,
      these findings reveal shared and divergent roles for epigenetic features and
      transcription factors in AgR V(D)J recombination and provide avenues for further
      investigation of chromatin signatures that may underpin V(D)J-mediated
      chromosomal translocations.

PMID- 29204144
TI  - All-Trans Retinoic Acid Promotes an M1- to M2-Phenotype Shift and Inhibits
      Macrophage-Mediated Immunity to Leishmania major.
AB  - As key cells, able to host and kill Leishmania parasites, inflammatory
      monocytes/macrophages are potential vaccine and therapeutic targets to improve
      immune responses in Leishmaniasis. Macrophage phenotypes range from M1, which
      express NO-mediated microbial killing, to M2 macrophages that might help
      infection. Resistance to Leishmaniasis depends on Leishmania species, mouse
      strain, and both innate and adaptive immunity. C57BL/6 (B6) mice are resistant
      and control infection, whereas Leishmania parasites thrive in BALB/c mice, which
      are susceptible to develop cutaneous lesions in the course of infection with
      Leishmania major, but not upon infection with Leishmania braziliensis. Here, we
      investigated whether a deficit in early maturation of inflammatory monocytes into
      macrophages in BALB/c mice underlies increased susceptibility to L. major versus
      L. braziliensis parasites. We show that, after infection with L. braziliensis,
      monocytes are recruited to peritoneum, differentiate into macrophages, and
      develop an M1 phenotype able to produce proinflammatory cytokines in both B6 and
      BALB/c mice. Nonetheless, more mature macrophages from B6 mice expressed
      inducible NO synthase (iNOS) and higher NO production in response to L.
      braziliensis parasites, whereas BALB/c mice developed macrophages expressing an
      incomplete M1 phenotype. By contrast, monocytes recruited upon L. major infection
      gave rise to immature macrophages that failed to induce an M1 response in BALB/c
      mice. Overall, these results are consistent with the idea that resistance to
      Leishmania infection correlates with improved maturation of macrophages in a
      mouse-strain and Leishmania-species dependent manner. All-trans retinoic acid
      (ATRA) has been proposed as a therapy to differentiate immature myeloid cells
      into macrophages and help immunity to tumors. To prompt monocyte to macrophage
      maturation upon L. major infection, we treated B6 and BALB/c mice with ATRA.
      Unexpectedly, treatment with ATRA reduced proinflammatory cytokines, iNOS
      expression, and parasite killing by macrophages. Moreover, ATRA promoted an M1 to
      M2 transition in bone marrow-derived macrophages from both strains. Therefore,
      ATRA uncouples macrophage maturation and development of M1 phenotype and
      downmodulates macrophage-mediated immunity to L. major parasites. Cautions should
      be taken for the therapeutic use of ATRA, by considering direct effects on innate
      immunity to intracellular pathogens.

PMID- 29204146
TI  - Intracellular S100A9 Promotes Myeloid-Derived Suppressor Cells during Late
      Sepsis.
AB  - Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell
      (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA
      and intracellular protein levels increase during early sepsis and remain elevated
      in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later
      chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this
      study was to determine whether intracellular S100A9 protein might sustain
      Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis. We used a chronic
      model of sepsis in mice to show that S100A9 release from MDSCs and circulating
      phagocytes decreases after early sepsis and that targeting the S100a9 gene
      improves survival. Surprisingly, we find that intracellular S100A9 protein
      translocates from the cytosol to nucleus in Gr1+CD11b+ MDSCs during late sepsis
      and promotes expression of miR-21 and miR-181b immune repressor mediators. We
      further provide support of this immunosuppression pathway in human sepsis. This
      study may inform a new therapeutic target for improving sepsis outcome.

PMID- 29204145
TI  - Molecular Signatures of Immunity and Immunogenicity in Infection and Vaccination.
AB  - Vaccinology aims to understand what factors drive vaccine-induced immunity and
      protection. For many vaccines, however, the mechanisms underlying immunity and
      protection remain incompletely characterized at best, and except for neutralizing
      antibodies induced by viral vaccines, few correlates of protection exist. Recent
      omics and systems biology big data platforms have yielded valuable insights in
      these areas, particularly for viral vaccines, but in the case of more complex
      vaccines against bacterial infectious diseases, understanding is fragmented and
      limited. To fill this gap, the EC supported ADITEC project
      (http://www.aditecproject.eu/;
      http://stm.sciencemag.org/content/4/128/128cm4.full) featured a work package on
      "Molecular signatures of immunity and immunogenicity," aimed to identify key
      molecular mechanisms of innate and adaptive immunity during effector and memory
      stages of immune responses following vaccination. Specifically, technologies were
      developed to assess the human immune response to vaccination and infection at the
      level of the transcriptomic and proteomic response, T-cell and B-cell memory
      formation, cellular trafficking, and key molecular pathways of innate immunity,
      with emphasis on underlying mechanisms of protective immunity. This work
      intersected with other efforts in the ADITEC project. This review summarizes the
      main achievements of the work package.

PMID- 29204147
TI  - Early Flowering as a Drought Escape Mechanism in Plants: How Can It Aid Wheat
      Production?
AB  - Drought escape (DE) is a classical adaptive mechanism which involves rapid plant
      development to enable the completion of the full life-cycle prior to a coming
      drought event. This strategy is widely used in populations of native plants, and
      is also applicable to cereal crops such as wheat. Early flowering time and a
      shorter vegetative phase can be very important for wheat production in conditions
      of terminal drought since this can minimize exposure to dehydration during the
      sensitive flowering and post-anthesis grain filling periods. A gradual shift
      toward early flowering has been observed over the last century of wheat breeding
      in countries with a Mediterranean-type climate and frequent terminal drought.
      This trend is predicted to continue for wheat production in the coming years in
      response to global climate warming. The advantage of early flowering wheat is
      apparent under conditions of impending terminal drought, and modern varieties are
      significantly more productive due to minimization of the risk associated with
      drought stress. Under favorable conditions, a short vegetative phase can result
      in reduced plant biomass due to the reduction in time available for
      photosynthetic production and seed nutrient accumulation. However, high yield
      potential has been reported for the development of both shallow and deep roots,
      representing plasticity in response to drought in combination with the early
      flowering trait. Wheat productivity can be high both in well-watered and drought
      affected field trials, where an efficient strategy of DE was associated with
      quick growth, yield potential and water use efficiency. Therefore, early
      flowering provides a promising strategy for the production of advanced drought
      adapted wheat cultivars.

PMID- 29204149
TI  - Diversity in Grain Amaranths and Relatives Distinguished by Genotyping by
      Sequencing (GBS).
AB  - The genotyping by sequencing (GBS) method has become a molecular marker
      technology of choice for many crop plants because of its simultaneous discovery
      and evaluation of a large number of single nucleotide polymorphisms (SNPs) and
      utility for germplasm characterization. Genome representation and complexity
      reduction are the basis for GBS fingerprinting and can vary by species based on
      genome size and other sequence characteristics. Grain amaranths are a set of
      three species that were domesticated in the New World to be high protein, pseudo
      cereal grain crops. The goal of this research was to employ the GBS technique for
      diversity evaluation in grain amaranth accessions and close relatives from six
      Amaranthus species and determine genetic differences and similarities between
      groupings. A total of 10,668 SNPs were discovered in 94 amaranth accessions with
      ApeKI complexity reduction and 10X genome coverage Illumina sequencing. The
      majority of the SNPs were species specific with 4,568 and 3,082 for the two grain
      amaranths originating in Central America Amaranthus cruentus and A.
      hypochondriacus and 3,284 found amongst both A. caudatus, originally domesticated
      in South America, and its close relative, A. quitensis. The distance matrix based
      on shared alleles provided information on the close relationships of the two
      cultivated Central American species with each other and of the wild and
      cultivated South American species with each other, as distinguished from the
      outgroup with two wild species, A. powellii and A. retroflexus. The GBS data also
      distinguished admixture between each pair of species and the geographical origins
      and seed colors of the accessions. The SNPs we discovered here can be used for
      marker development for future amaranth study.

PMID- 29204148
TI  - Insights into the Mechanisms Underlying Boron Homeostasis in Plants.
AB  - Boron is an essential element for plants but is toxic in excess. Therefore,
      plants must adapt to both limiting and excess boron conditions for normal growth.
      Boron transport in plants is primarily based on three transport mechanisms across
      the plasma membrane: passive diffusion of boric acid, facilitated diffusion of
      boric acid via channels, and export of borate anion via transporters. Under boron
      -limiting conditions, boric acid channels and borate exporters function in the
      uptake and translocation of boron to support growth of various plant species. In
      Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and
      polarized toward soil and stele, respectively, in various root cells, for
      efficient transport of boron from the soil to the stele. Importantly, sufficient
      levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation
      and proteolysis through endocytosis, respectively. In addition, borate exporters,
      such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from
      tissues and cells under conditions of excess boron. Thus, plants actively
      regulate intracellular localization and abundance of transport proteins to
      maintain boron homeostasis. In this review, the physiological roles and
      regulatory mechanisms of intracellular localization and abundance of boron
      transport proteins are discussed.

PMID- 29204150
TI  - Rhizobium Impacts on Seed Productivity, Quality, and Protection of Pisum sativum
      upon Disease Stress Caused by Didymella pinodes: Phenotypic, Proteomic, and
      Metabolomic Traits.
AB  - In field peas, ascochyta blight is one of the most common fungal diseases caused
      by Didymella pinodes. Despite the high diversity of pea cultivars, only little
      resistance has been developed until to date, still leading to significant losses
      in grain yield. Rhizobia as plant growth promoting endosymbionts are the main
      partners for establishment of symbiosis with pea plants. The key role of
      Rhizobium as an effective nitrogen source for legumes seed quality and quantity
      improvement is in line with sustainable agriculture and food security programs.
      Besides these growth promoting effects, Rhizobium symbiosis has been shown to
      have a priming impact on the plants immune system that enhances resistance
      against environmental perturbations. This is the first integrative study that
      investigates the effect of Rhizobium leguminosarum bv. viceae (Rlv) on phenotypic
      seed quality, quantity and fungal disease in pot grown pea (Pisum sativum)
      cultivars with two different resistance levels against D. pinodes through
      metabolomics and proteomics analyses. In addition, the pathogen effects on seed
      quantity components and quality are assessed at morphological and molecular
      level. Rhizobium inoculation decreased disease severity by significant reduction
      of seed infection level. Rhizobium symbiont enhanced yield through increased seed
      fresh and dry weights based on better seed filling. Rhizobium inoculation also
      induced changes in seed proteome and metabolome involved in enhanced P. sativum
      resistance level against D. pinodes. Besides increased redox and cell wall
      adjustments light is shed on the role of late embryogenesis abundant proteins and
      metabolites such as the seed triterpenoid Soyasapogenol. The results of this
      study open new insights into the significance of symbiotic Rhizobium interactions
      for crop yield, health and seed quality enhancement and reveal new metabolite
      candidates involved in pathogen resistance.

PMID- 29204152
TI  - Insights into the Drought and Heat Avoidance Mechanism in Summer-Dormant
      Mediterranean Tall Fescue.
AB  - Summer dormancy is an evolutionary response that some perennial cool-season
      grasses adopted as an avoidance strategy to escape summer drought and heat. It is
      correlated with superior survival after severe summer droughts in many perennial
      grass species originating from Mediterranean environments. Understanding the
      genetic mechanism and environmental determinants of summer dormancy is important
      for interpreting the evolutionary history of seasonal dormancy and for the
      development of genomic tools to improve the efficiency of genetic selection for
      this important trait. The objectives of this research are to assess morphological
      and biochemical attributes that seem to be specific for the characterization of
      summer dormancy in tall fescue, and to validate the hypothesis that genes
      underlying stem determinacy might be involved in the mechanism of summer
      dormancy. Our results suggest that vernalization is an important requirement in
      the onset of summer dormancy in tall fescue. Non-vernalized tall fescue plants do
      not exhibit summer dormancy as vernalized plants do and behave more like summer
      active types. This is manifested by continuation of shoot growth and high root
      activity in water uptake during summer months. Therefore, summer dormancy in tall
      fescue should be tested only in plants that underwent vernalization and are not
      subjected to water deficit during summer months. Total phenolic concentration in
      tiller bases (antioxidants) does not seem to be related to vernalization. It is
      most likely an environmental response to protect meristems from oxidative stress.
      Sequence analysis of the TFL1 homolog CEN gene from tall fescue genotypes
      belonging to summer-dormant and summer-active tall fescue types showed a unique
      deletion of three nucleotides specific to the dormant genotypes. Higher tiller
      bud numbers in dormant plants that were not allowed to flower and complete the
      reproductive cycle, confirmed that stem determinacy is a major component in the
      mechanism of summer dormancy. The number of variables identified in these studies
      as potential players in summer dormancy in tall fescue including vernalization,
      TFL1/CEN, water status, and protection from oxidative stress are a further
      confirmation that summer dormancy is a quantitative trait controlled by several
      genes with varying effects and prone to genotype by environment interactions.

PMID- 29204151
TI  - An Alcohol Dehydrogenase Gene from Synechocystis sp. Confers Salt Tolerance in
      Transgenic Tobacco.
AB  - Synechocystis salt-responsive gene 1 (sysr1) was engineered for expression in
      higher plants, and gene construction was stably incorporated into tobacco plants.
      We investigated the role of Sysr1 [a member of the alcohol dehydrogenase (ADH)
      superfamily] by examining the salt tolerance of sysr1-overexpressing (sysr1-OX)
      tobacco plants using quantitative real-time polymerase chain reactions, gas
      chromatography-mass spectrometry, and bioassays. The sysr1-OX plants exhibited
      considerably increased ADH activity and tolerance to salt stress conditions.
      Additionally, the expression levels of several stress-responsive genes were
      upregulated. Moreover, airborne signals from salt-stressed sysr1-OX plants
      triggered salinity tolerance in neighboring wild-type (WT) plants. Therefore,
      Sysr1 enhanced the interconversion of aldehydes to alcohols, and this occurrence
      might affect the quality of green leaf volatiles (GLVs) in sysr1-OX plants.
      Actually, the Z-3-hexenol level was approximately twofold higher in sysr1-OX
      plants than in WT plants within 1-2 h of wounding. Furthermore, analyses of WT
      plants treated with vaporized GLVs indicated that Z-3-hexenol was a stronger
      inducer of stress-related gene expression and salt tolerance than E-2-hexenal.
      The results of the study suggested that increased C6 alcohol (Z-3-hexenol)
      induced the expression of resistance genes, thereby enhancing salt tolerance of
      transgenic plants. Our results revealed a role for ADH in salinity stress
      responses, and the results provided a genetic engineering strategy that could
      improve the salt tolerance of crops.

PMID- 29204153
TI  - Biomass Allocation Patterns Are Linked to Genotypic Differences in Whole-Plant
      Transpiration Efficiency in Sunflower.
AB  - Increased transpiration efficiency (the ratio of biomass to water transpired, TE)
      could lead to increased drought tolerance under some water deficit scenarios.
      Intrinsic (i.e., leaf-level) TE is usually considered as the primary source of
      variation in whole-plant TE, but empirical data usually contradict this
      assumption. Sunflower has a significant variability in TE, but a better knowledge
      of the effect of leaf and plant-level traits could be helpful to obtain more
      efficient genotypes for water use. The objective of this study was, therefore, to
      assess if genotypic variation in whole-plant TE is better related to leaf- or
      plant-level traits. Three experiments were conducted, aimed at verifying the
      existence of variability in whole-plant TE and whole-plant and leaf-level traits,
      and to assess their correlation. Sunflower public inbred lines and a segregating
      population of recombinant inbred lines were grown under controlled conditions and
      subjected to well-watered and water-deficit treatments. Significant genotypic
      variation was found for TE and related traits. These differences in whole-plant
      transpiration efficiency, both between genotypes and between plants within each
      genotype, showed no association to leaf-level traits, but were significantly and
      negatively correlated to biomass allocation to leaves and to the ratio of leaf
      area to total biomass. These associations are likely of a physiological origin,
      and not only a consequence of genetic linkage in the studied population. These
      results suggest that genotypic variation for biomass allocation could be
      potentially exploited as a source for increased transpiration efficiency in
      sunflower breeding programmes. It is also suggested that phenotyping for TE in
      this species should not be restricted to leaf-level measurements, but also
      include measurements of plant-level traits, especially those related to biomass
      allocation between photosynthetic and non-photosynthetic organs.

PMID- 29204155
TI  - A Meta-Analysis of Adalimumab for Fistula in Crohn's Disease.
AB  - Purpose: This study aimed to evaluate the therapeutic value of adalimumab (ADA)
      for fistula in Crohn's disease (CD). Methods: A computerized search of electronic
      databases, including PubMed, Web of Science, Embase, Google scholar, and the
      Cochrane Library from 2000 to October 2016, was performed. Randomized controlled
      trials (rcts) or nonrandomized controlled trials (n-rcts) were included in this
      article to evaluate the role of ADA in the management of fistula in CD. The
      methodological index for nonrandomized studies (MINORS evaluation tools) was used
      to assess the quality of every study. Result: Overall, seven studies and 379
      patients comforted to the inclusion criteria of this meta-analysis. The result
      showed that 36% (95% CI: 0.31-0.41) of patients with complete fistula closure and
      31% (95% CI: 0.031-0.61) of patients with partial response were received in CD
      with ADA treatment. Conclusion: We concluded that ADA is effective and safe for
      the treatment of fistula in CD according to current evidence.

PMID- 29204156
TI  - Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope
      Presentation in Diffuse Large B Cell Lymphoma Patients.
AB  - Improved therapies are urgently needed for patients with diffuse large B cell
      lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen
      receptor T cell technology has fuelled demand for validated cancer epitopes.
      Immunogenic cancer testis antigens (CTAs), with their widespread expression in
      many tumours but highly restricted normal tissue distribution, represent
      attractive immunotherapeutic targets that may improve treatment options for DLBCL
      and other malignancies. Sperm protein 17 (Sp17), a CTA reported to be immunogenic
      in ovarian cancer and myeloma patients, is expressed in DLBCL. The aim of the
      present study was to investigate Sp17 epitope presentation via the presence of a
      cytotoxic T cell (CTL) and a CD4 T-helper (Th) response in DLBCL patients. A
      significant gamma-interferon CTL response was detected in peripheral blood
      mononuclear cells of 13/31 DLBCL patients following short-term cell stimulation
      with two novel HLA-A*0201 peptides and one previously reported HLA-A*0101
      restricted nine-mer Sp17 peptide. No significant responses were detected in the
      HLA-A*0201-negative DLBCL patients or four healthy subjects. A novel immunogenic
      20-mer CD4 Th Sp17 peptide was detected in 8/17 DLBCL patients. This is the first
      report of a CTL and a CD4 Th response to Sp17 in DLBCL and supports Sp17 as a
      potential immunotherapeutic target for DLBCL.

PMID- 29204158
TI  - Radiation treatment of prostate cancers - the contemporary role of modern
      brachytherapy techniques.

PMID- 29204157
TI  - Vitrification of Rhesus Macaque Mesenchymal Stem Cells and the Effects on Global
      Gene Expression.
AB  - Mesenchymal stem cells (MSCs) are one of the most promising adult stem cells for
      clinical application in a cell therapy. The development of large-scale
      cryopreservation techniques, such as vitrification, for MSCs is a prerequisite
      for clinical therapies. Dimethyl sulfoxide (DMSO) and ethylene glycol (EG) are
      two types of cryoprotectants widely used for cell vitrification. However, the
      effects of DMSO and EG on the biological characteristics and transcriptome
      profiles of MSCs after cryopreservation remain unknown. In the present study, the
      viability, immunophenotype of cell surface markers, proliferation,
      differentiation potency, and global gene expression of rhesus macaque bone marrow
      derived MSCs vitrified using DMSO and EG were studied. The results showed that
      vitrification did not affect the morphology, surface markers, and differentiation
      of the MSCs, and compared to DMSO, EG better protected cell viability and
      proliferation. Most importantly, vitrification resulted in changes in a large
      number of transcripts of MSCs either preserved using DMSO or EG. This report is
      the first to examine the effects of DMSO and EG on global gene expression in stem
      cells. These results will be beneficial to understanding the biological process
      involved in MSC vitrification and will contribute to improving cryopreservation
      protocols that maintain transcriptomic identity with high cryosurvival for
      preclinical research and clinical long-term storage.

PMID- 29204159
TI  - What pelvic radiation disease symptoms are experienced by patients receiving
      external beam radiotherapy and a high-dose-rate brachytherapy boost for prostate
      cancer?
AB  - Purpose: Research describing proctitis or pelvic radiation disease symptoms of
      prostate cancer patients one year after external beam radiotherapy (EBRT) plus
      high-dose-rate (HDR) brachytherapy is limited. This study aimed to assess
      prostate cancer patients' pelvic radiation disease symptoms from baseline to 12
      months post-radiotherapy. Material and methods: Men with prostate cancer referred
      for EBRT and HDR brachytherapy were recruited. Patients' age, diagnosis, staging,
      PSA, past medical history, and treatment were recorded. Pelvic radiation disease
      symptoms were assessed via the Phase III EORTC proctitis module. Patients
      completed questionnaires before radiotherapy (baseline) and at one, three, six,
      and 12 months afterwards. To assess acute toxicity, symptoms one month after
      radiotherapy were compared with baseline. To assess post-treatment recovery,
      symptoms at three, six, and 12 months post radiotherapy were compared with one
      month. Symptom changes over time were assessed with linear mixed effect models.
      Results: Two hundred and sixty-six patients were recruited. Mean scores were
      below 2 at all time-points. The proportion of patients experiencing symptoms were
      also calculated. Linear mixed effect models showed that time-point, age, and T
      stage were associated with some pelvic radiation disease symptoms. Conclusions:
      Patients receiving EBRT plus HDR brachytherapy to the prostate experienced mild
      pelvic radiation disease symptoms. Determining the proportion of patients with
      symptoms provided the most meaningful data.

PMID- 29204154
TI  - Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants
      in Parkinson's Disease.
AB  - Parkinson's disease (PD) is a devastating neurological movement disorder. Since
      its first discovery 200 years ago, genetic and environmental factors have been
      identified to play a role in PD development and progression. Although genetic
      studies have been the predominant driving force in PD research over the last few
      decades, currently only a small fraction of PD cases can be directly linked to
      monogenic mutations. The remaining cases have been attributed to other risk
      associated genes, environmental exposures and gene-environment interactions,
      making PD a multifactorial disorder with a complex etiology. However, enormous
      efforts from global research have yielded significant insights into pathogenic
      mechanisms and potential therapeutic targets for PD. This review will highlight
      mitochondrial dysfunction as a common pathway involved in both genetic mutations
      and environmental toxicants linked to PD.

PMID- 29204160
TI  - Does supplemental external beam radiation therapy impact urinary, bowel, and
      erectile function following permanent prostate brachytherapy?: results of two
      prospective randomized trials.
AB  - Purpose: To evaluate the impact of supplemental external beam radiation therapy
      (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and
      erectile function. Material and methods: Patient administered urinary, bowel, and
      erectile quality of life (QoL) instrument were obtained prior to treatment and
      following brachytherapy. The study population was comprised of the 457 patients
      who were alive as of June 2016, had been randomized to two markedly different
      supplemental EBRT dose regimens and a third arm without supplemental EBRT, and
      had completed the June 2016 QoL survey. The need for urinary or bowel surgical
      intervention was prospectively recorded during routine follow-up. Multiple
      parameters were evaluated for effect on outcomes. Results: The urinary catheter
      was removed on day 0 in 92.1% of patients and 0.4% required a post-implant
      transurethral prostatic resection (TURP). On average, the International Prostate
      Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral
      strictures was 5.3%. No significant differences were discerned between baseline
      and post-implant rectal function assessment score (RFAS), and no patient
      developed a rectal ulcer or fistula. The 10-year potency preservation rate was
      50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function.
      Urethral strictures were most closely related to bulbomembranous urethral
      brachytherapy doses, post-implant rectal function to pre-implant hemorroidal
      bleeding, and RFAS and erectile function to pre-brachytherapy international index
      of erectile function and age. Conclusions: Supplemental EBRT did not
      significantly effect catheter dependency, IPSS resolution, urethral stricture
      rate, the need for post-implant TURP, bowel, or erectile function. Careful
      attention to brachytherapy dose distributions appears to be most important in
      minimizing post-brachytherapy morbidity.

PMID- 29204162
TI  - Treatment plan dosimetric impact after catheter stretch during multi-catheter
      interstitial breast brachytherapy.
AB  - Purpose: Nylon 6/6 interstitial brachytherapy catheters may stretch when exposed
      to moisture, mechanical tension, and body temperature. The purpose of this study
      is to evaluate the magnitude of catheter stretch during a course of multi
      catheter interstitial breast brachytherapy for nylon 6/6 treatment catheters, and
      to assess the impact this has on treatment plan dosimetry. Material and methods:
      Catheters were exposed to water at 37 degrees C for six days and the internal
      catheter length change (DeltaL_W) was measured daily. Additionally, the measured
      internal catheter length change (DeltaL_P), performed prior to each treatment
      fraction, for seven interstitial breast brachytherapy patients (total of 76
      catheters) were retrospectively analyzed. The maximum length change seen in
      DeltaL_P and DeltaL_W were introduced as a source positional error to
      retrospective treatment plans, and treatment plan dosimetry was analyzed.
      Results: DeltaL_W and DeltaL_P were on average +4.0% and +1.6% of the catheter
      lengths in water or tissue after 48 hours. Weak correlation was seen between the
      average DeltaL_P per catheter and both the catheter length within tissue (rho =
      0.36, p = 0.0007), and the mid-catheter depth in tissue (rho = 0.42, p < 0.0001).
      The D90CTV decreased 1.5% (p < 0.05) and 8.2% (p < 0.05) when the DeltaL_P and
      DeltaL_W were introduced to the initial plans. Conclusions: Nylon 6/6 catheters
      stretch during a course of multi-catheter interstitial breast brachytherapy
      treatment. The observed stretch may affect treatment plan dosimetry, if the
      catheter internal length is only measured immediately after the insertion.
      Additional catheter length checks are recommended to verify the actual catheter
      internal length during the treatment.

PMID- 29204161
TI  - Dosimetry advantages of intraoperatively built custom-linked seeds compared with
      loose seeds in permanent prostate brachytherapy.
AB  - Purpose: The aim of this study was to compare the implant quality between
      intraoperatively built custom-linked seeds (IBCL) and loose seeds (LS)
      retrospectively. Material and methods: This study included 74 prostate cancer
      patients who were treated with permanent prostate brachytherapy (PPB) using IBCL
      (n = 37) or LS (n = 37) between July 2014 and June 2016. Dose-volume histogram
      (DVH) parameters, seed migration, and operation time were compared between the
      IBCL and LS groups. In addition to the standard target volume of the whole
      prostate gland, DVH parameters for prostate plus a 3 mm margin (CTV) were
      evaluated. Results: In intraoperative planning, prostate V150 was lower (54.8%
      vs. 59.6%, p = 0.027), and CTV V100 (88.1% vs. 85.6%, p = 0.019) and D90 (98.5%
      vs. 92.6%, p = 0.0033) were higher in the IBCL group compared with in the LS
      group. In post-implant dosimetry, prostate V100 (96.9% vs. 95.2%, p = 0.020), CTV
      V100 (85.6% vs. 81.7%, p = 0.046), and CTV D90 (94.2% vs. 86.5%, p < 0.001) were
      higher, and prostate V150 (57.1% vs. 64.5%, p = 0.0051) and CTV V150 (31.5% vs.
      35.7%, p = 0.046) were lower in the IBCL group compared with in the LS group.
      Regarding DVH changes between intraoperative planning and post-implant dosimetry,
      the decrease in prostate D90 was significantly lower in the IBCL group than in
      the LS group (-1.16% vs. -4.17%, p < 0.001). For the IBCL group, the operation
      time was slightly but significantly longer than that for the LS group (50.5
      minutes vs. 43.7 minutes, p = 0.011). However, the seed migration rate was
      significantly lower in the IBCL group than in the LS group (5% vs. 41%, p <
      0.001). Conclusions: Intraoperatively built custom-linked is more advantageous
      than LS in terms of dosimetric parameters and migration.

PMID- 29204163
TI  - Efficacy of single-stage breast-conserving treatment using multicatheter partial
      breast brachytherapy evaluated by GEC-ESTRO phase 3 trial.
AB  - Purpose: The GEC-ESTRO has reported the equivalent outcomes of partial breast
      irradiation (PBI) using multicatheter interstitial brachytherapy (MCB) to whole
      breast irradiation (WBI) in breast-conserving therapy (BCT). We performed single
      stage BCT with partial breast brachytherapy by intraoperative catheter placement.
      After the categorization of patients into inclusion and exclusion criteria on
      this trial, our databases were evaluated in order to translate it to Japanese
      patients. Material and methods: Patients undergoing BCT were retrospectively
      examined between November 2007 and December 2015. The technique is an open-cavity
      implant with a dose of 32 Gy in 8 fractions. The 4-year clinical outcomes of MCB
      PBI were evaluated in the 2 distinct categories, and the comparison of the
      outcomes of MCB-PBI with WBI was performed in patients with unfavorable features.
      Results: Of a total of 501 lesions undergoing BCT, 301 lesions were treated with
      MCB-PBI and 200 lesions with WBI. At the median follow-up time of 52 months, the
      4-year rate of ipsilateral breast tumor recurrence (IBTR)-free, disease-free
      (DFS), and overall survival (OS) in patients with MCB-PBI and WBI were 98.9% vs.
      98.0% (p = 0.56), 97.0% vs. 95.3% (p = 0.78), and 99.6% vs. 98.2% (p = 0.38),
      respectively. Although in exclusion cohort treated with MCB-PBI, IBTR-free, and
      disease-free survival were significantly worse than in inclusion cohort, non
      significantly worse outcomes was demonstrated than in exclusion cohort with WBI;
      IBTR-free survival (95.0% vs. 97.2%, p = 0.24), and disease-free survival (95.0%
      vs. 95.8%, p = 0.31). Conclusions: Single-stage BCT using MCB-PBI offered similar
      tumor control rates compering to WBI. However, further research is needed to
      define the benefit for patients with an exclusion criteria.

PMID- 29204164
TI  - Comparison of dose volume parameters evaluated using three forward planning -
      optimization techniques in cervical cancer brachytherapy involving two
      applicators.
AB  - Purpose: This study is intended to compare dose-volume parameters evaluated using
      different forward planning- optimization techniques, involving two applicator
      systems in intracavitary brachytherapy for cervical cancer. It looks for the best
      applicator-optimization combination to fulfill recommended dose-volume objectives
      in different high-dose-rate (HDR) fractionation schedules. Material and methods:
      We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients
      in two fractions of brachytherapy. Six plans were generated for each patient
      utilizing 3 forward optimization techniques for each applicator used: equal dwell
      weight/times ('no optimization'), 'manual dwell weight/times', and 'graphical'.
      Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose
      volume and dose point parameters were compared. Results: Without graphical
      optimization, maximum width and thickness of volume enclosed by 100% isodose
      line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum,
      median, and average dose to both rectum and bladder are significantly higher with
      Fletcher applicator. Even if it is done, dose to both points B, minimum dose to
      CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc,
      minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder
      remain significantly higher with this applicator. Dose to bladder point is
      similar (p > 0.05) between two applicators, after all optimization techniques.
      Conclusions: Fletcher applicator generates higher dose to both CTV and organs at
      risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum
      is possible using graphical optimization only during selected HDR fractionation
      schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid
      colon always gets permissible dose. Contrarily, graphical optimization with ring
      applicators fulfills all dose volume objectives in all HDR fractionations
      practiced.

PMID- 29204165
TI  - Throwing the dart blind-folded: comparison of computed tomography versus magnetic
      resonance imaging-guided brachytherapy for cervical cancer with regard to dose
      received by the 'actual' targets and organs at risk.
AB  - Purpose: Computed tomography (CT) is inferior to magnetic resonance imaging (MRI)
      in cervical tumor delineation, but similar in identification of organs at risk
      (OAR). The trend to over-estimate high-risk and low-risk clinical target volume
      (HRCTV, IRCTV) on CT can lead to under-estimation of dose received by 90% (D90)
      of the 'actual' CTV. This study aims to evaluate whether CT-guided planning
      delivers adequate dose to the 'actual' targets while spares the OAR similarly.
      Material and methods: MRI-guided high-dose-rate image-guided brachytherapy (IGBT)
      was performed in 11 patients. The pre-brachytherapy CTs were retrospectively
      contoured to generate CT-guided plans. MRI-based contours (HRCTVmri, IRCTVmri,
      bladdermri, rectummri, and sigmoidmri) were fused to CT plans for dosimetric
      comparison with MRI-guided plans. Paired 2-tailed t-test and Wilcoxon signed-rank
      test were used to analyze data. Results: 63.6% of CT plans achieved the
      HRCTVmriD90 constraint (>= 7.2 Gy in one fraction), compared with 90.9% for MRI
      plans. > 90% of both modalities achieved the OAR's constraints (EMBRACE). The
      percentage of CT and MRI plans that achieved the aims (EMBRACE II) for bladder,
      rectum, and sigmoid were 36.4% vs. 81.8%, 63.6% vs. 63.6%, and 72.7% vs. 72.7%,
      respectively. There were no statistically significant differences in HRCTVmriD90,
      IRCTVmriD90, or dose received by the most exposed 2 cm3 (D2cc) of OARmri between
      the modalities. Excluding the CT plans not achieving HRCTVmriD90 constraint,
      there were significant increase in bladdermriD2cc, rectummriD2cc, and
      sigmoidmriD2cc, compared with MRI plans (0.9 Gy/Fr, 95% CI 0.2-1.5, p = 0.018;
      0.9 Gy/Fr, 95% CI 0.3-1.4, p = 0.009; 0.5 Gy/Fr, 95% CI 0.2-0.9, p = 0.027,
      respectively). Conclusions: MRI-based IGBT remains the gold standard. CT planning
      may compromise HRCTVmriD90 or increase OARmriD2cc, which could decrease local
      control or increase treatment toxicity.

PMID- 29204166
TI  - Patterns of care and survival outcomes after treatment for uveal melanoma in the
      post-coms era (2004-2013): a surveillance, epidemiology, and end results
      analysis.
AB  - Purpose: The Collaborative Ocular Melanoma Study (COMS) established modern
      treatment recommendations for uveal melanoma. We aim to evaluate patterns of care
      and survival outcomes in the time after COMS. Material and methods: The
      retrospective study population includes 2,611 patients in the SEER database
      treated for uveal melanoma between 2004-2013. Patients stage were T1-4N0M0. Data
      analyzed included age, clinical stage, tumor size, race, and treatment.
      Treatments included enucleation (EN) and globe preserving therapy (GPT), which
      consisted of limited surgical resection or ablation (LSRA), external beam
      radiation (EBRT), or brachytherapy (BT). Patients treated with radiation may
      receive radiation therapy alone (RTA) or radiation therapy and supplemental laser
      therapy (RT+SLT). We evaluated disease specific survival (DSS) and overall
      survival (OS) using log-rank statistics, and Cox univariate and multivariate
      analysis. Results: The median follow-up was 44 months. Treatment strategy was EN
      in 538 (20.6%) patients, LSRA in 80 (3.1%), EBRT in 609 (23.3%), and BT in 1,384
      (53.0%). 1,876 patients received RTA and 117 received RT+SLT. Enucleation was
      associated with inferior DSS and OS compared to GPT in multivariate analysis
      (MVA) (p < 0.01). Limited surgical resection or ablation and radiation had
      similar DSS and OS. Brachytherapy and EBRT had similar DSS and OS. Radiation
      therapy and supplemental laser therapy was associated with improved DSS compared
      to RTA in UVA (p = 0.03), but not MVA. The 5-year DSS for enucleation, RTA, and
      RT+SLT were 66.7%, 87.0%, and 94.7% (p < 0.01), respectively. Conclusions: Globe
      preserving treatments such as limited surgery or radiation are commonly utilized
      alternatives to enucleation, and resulted in favorable survival outcomes.
      Additional research is required to compare the outcomes of the various globe
      preserving treatment strategies.

PMID- 29204167
TI  - Interstitial brachytherapy for orbital soft tissue sarcoma: an innovative
      technique.
AB  - Purpose: To report an innovative technique of interstitial brachytherapy
      developed for treatment of orbital soft tissue tumors. Material and methods: A 4
      month-old child diagnosed with rhabdomyosarcoma of orbit was treated with
      multiagent chemotherapy (CTh) and brachytherapy. Pre-planning computed tomography
      (CT) images were obtained and clinical target volume (CTV) was defined using the
      pre-treatment magnetic resonance imaging (MRI). Brachytherapy plan was generated
      for deciding optimal catheter placement. With the child under general anesthesia,
      catheter entry points were extrapolated and marked on the skin as determined from
      the pre-planning CT scan. Implantation of catheters was performed as per pre
      determined catheter position and depths. Brachytherapy plan was generated and
      evaluated using dose volume histograms (DVH). A comparative external beam
      radiotherapy (EBRT) plan using RapidArc was also generated for the CTV with a 3
      mm margin as the planning target volume (PTV). Results: The mean CTV dose with
      brachytherapy was 158% compared to 101% with RapidArc. The CTV V100 was 90% for
      brachytherapy vs. 95% for RapidArc. The mean dose to Lt Lens were 51% and 60%,
      respectively for brachytherapy and RapidArc, while the corresponding mean doses
      to the bony orbit were 39% and 68%, respectively. Follow-up MRI at 3 months
      showed complete response of the tumor. Conclusions: Interstitial brachytherapy
      for orbit using this innovative technique is a safe and effective modality of
      local treatment for appropriately selected orbital soft tissue tumors.
      Brachytherapy resulted in excellent disease control with significant reduction of
      dose to surrounding ocular structures compared to EBRT.

PMID- 29204168
TI  - Pre-plan technique feasibility in multi-interstitial/endocavitary perineal
      gynecological brachytherapy.
AB  - Purpose: To present the implementation of a magnetic resonance imaging (MRI) pre
      planning technique in multi-interstitial perineal and endocavitary gynecological
      brachytherapy. Material and methods: We used a new fully MRI-compatible
      applicator that is capable to engage titanium needles, and an intrauterine
      tandem, developed in our department for the treatment of gynecological cervical
      cancer patients. This applicator is an attempt to combine the technical
      advantages of the Martinez universal perineal interstitial template (MUPIT) with
      the improvement in dose distribution by adding an intrauterine probe with the
      imaging advantages of MRI-based brachytherapy, thus preserving the stability,
      geometry, and robustness of the implant, avoiding possible errors of free-hand
      needle placement. A pre-brachytherapy MRI T2 acquisition is carried out with the
      template in place 3-5 days before the implant. On this image set, clinical target
      volume (CTV) is drawn. The required needles and their depths are selected
      accordingly to encompass the CTV (as conformal as possible). To facilitate this
      task, a Java based application linked to the treatment planning system has been
      developed. From this procedure, each needle identification and its depth are
      obtained previously to the implantation. With this information, the radiation
      oncologist proceeds with implant and then, a post-implant MRI is carried out, in
      which the contouring, needles, tandem reconstruction, and optimization are
      established. Results: This pre-planning procedure has been successfully applied
      in 10 patients. An excellent reproduction of the virtual pre-planning has been
      achieved. Conclusions: We describe a virtual pre-planning technique using a multi
      interstitial and endocavitary perineal template. It is based on a virtual work
      with MRI images. This procedure has shown to be feasible and efficient in
      clinical practice by facilitating the work of specialists, and reducing
      uncertainties of the application.

PMID- 29204169
TI  - Independent assessment of source position for gynecological applicator in high
      dose-rate brachytherapy.
AB  - Purpose: The aim of this study is to describe a phantom designed for independent
      examination of a source position in brachytherapy that is suitable for inclusion
      in an external auditing program. Material and methods: We developed a phantom
      that has a special design and a simple mechanism, capable of firmly fixing a
      radiochromic film and tandem-ovoid applicators to assess discrepancies in source
      positions between the measurements and treatment planning system (TPS). Three
      tests were conducted: 1) reproducibility of the source positions (n = 5); 2)
      source movements inside the applicator tube; 3) changing source position by
      changing curvature of the transfer tubes. In addition, as a trial study, the
      phantom was mailed to 12 institutions, and 23 trial data sets were examined. The
      source displacement DeltaX and DeltaY (reference = TPS) were expressed according
      to the coordinates, in which the positive direction on the X-axis corresponds to
      the external side of the applicator perpendicular to source transfer direction Y
      axis. Results: Test 1: The 1sigma fell within 1 mm irrespective of the dwell
      positions. Test 2: DeltaX were greater around the tip of the applicator owing to
      the source cable. Test 3: All of the source position changes fell within 1 mm.
      For postal audit, the mean and 1.96sigma in DeltaX were 0.8 and 0.8 mm,
      respectively. Almost all data were located within a positive region along the X
      axis due to the source cable. The mean and 1.96sigma in DeltaY were 0.3 and 1.6
      mm, respectively. The variance in DeltaY was greater than that in DeltaX, and
      large uncertainties exist in the determination of the first dwell position. The
      95% confidence limit was 2.1 mm. Conclusions: In HDR brachytherapy, an
      effectiveness of independent source position assessment could be demonstrated.
      The 95% confidence limit was 2.1 mm for a tandem-ovoids applicator.

PMID- 29204171
TI  - Magnetic resonance imaging metal artifact reduction for eye plaque patient with
      dental braces.
AB  - Purpose: To determine if metal artifact reduction can minimize magnetic
      susceptibility artifacts in the orbits for an eye plaque brachytherapy patient
      with metallic dental braces. Material and methods: A 62-year-old female patient
      with a choroidal melanoma in the right eye received a 1.5 T magnetic resonance
      imaging (MRI) simulation for 3D eye plaque brachytherapy planning. The protocol
      included conventional 3D T1-weighted and 2D T2-weighted MRIs. A vendor-supplied
      T2-weighted metal artifact reduction sequence was added to the protocol to reduce
      magnetic susceptibility artifacts from the metallic dental braces. The metal
      artifact reduction sequence combined turbo spin echo acquisitions, high RF
      excitation and readout bandwidths, and view angle tilting and slice encoding for
      metal artifact correction with z-shimming to correct in-plane and through-plane
      image distortions, respectively. Results: Dental braces caused significant signal
      loss and image distortion in the orbits on the conventional T1-weighted and T2
      weighted MRIs, and the MRIs were unusable for treatment planning. The metal
      artifact reduction sequence with 13 z-phase encodes minimized distortion and
      signal loss in the orbits, allowing the tumor to be clearly delineated.
      Conclusions: T2-weighted MRI with metal artifact reduction was successfully
      applied to minimize artifacts in the orbits resulting from the dental braces,
      thus allowing the MRIs to be used in 3D brachytherapy treatment planning.

PMID- 29204170
TI  - Locally advanced squamous cell cervical cancer in a patient with septate uterus.
AB  - A 33-year-old premenopausal multiparous woman with the history of septate uterus
      was referred to the hospital with menorrhagia and inter-menstrual bleeding
      occurring for the last 6 months. Work-up revealed a stage IIB cervical cancer.
      The patient underwent curative chemo/radiotherapy. The patient's septate uterus
      presented several difficulties during application. Brachytherapy was applied
      using standard computed tomography-compatible tandem and ovoids. The high-risk
      clinical target volume (HR-CTV), intermediate risk CTV, and organs at risk were
      contoured according to the Groupe Europeen de Curietherapie - European Society
      for Radiology and Oncology (GEC-ESTRO) guidelines. Treatment was performed via 3
      dimensional high-dose-rate technique with 192Ir, with brachytherapy dose of 28 Gy
      in 4 fractions/7 Gy each, prescribed to the HR-CTV. Treatment was well tolerated
      with manageable acute toxicities. To the best of our knowledge, the current case
      is the second case of septate uterus with locally advanced cervical carcinoma.
      Due to the lack of guidelines about brachytherapy applications in patients with
      uterine anomaly and owing to the anatomical anomaly, brachytherapy application is
      challenging in this patients population.

PMID- 29204172
TI  - Protective effects of coenzyme Q10 and L-carnitine against statin-induced
      pancreatic mitochondrial toxicity in rats.
AB  - Statins are widely used in patients with hyperlipidemia and whom with high risk
      of cardiovascular diseases. Unfortunately, statins also exert some adverse
      effects on the liver and pancreas and enhance the risk of type 2 diabetes
      mellitus. The objective of the present research was to investigate the protective
      effects of coenzyme Q10 (Co-Q10) and L-carnitine (LC) on statins induced toxicity
      on pancreatic mitochondria in vivo. Seven groups of male Wistar rats received
      atorvastatin (20 mg/kg, p.o.), atorvastatin + Co-Q10 (10 mg/kg, i.p.),
      atorvastatin + LC (500 mg/kg, i.p.), lovastatin (80 mg/kg, p.o), lovastatin + Co
      Q10 (10 mg/kg, i.p.), and lovastatin + LC (500 mg/kg, i.p.). Serum glucose and
      insulin levels were measured before and after two weeks of treatment, while the
      pancreas was removed and toxic effects of statins, as well as the protective
      effects of Co-Q10 and LC were assessed. The results showed that atorvastatin and
      lovastatin significantly increased glucose level and decreased insulin secretion.
      The glucose level in Co-Q10 and LC groups was significantly lower than statins
      alone groups. The findings also showed that statin groups had higher rate of
      pancreatic toxicity including higher level of reactive oxygen species production,
      decreased cytochrome c oxidase activity, collapse of mitochondrial membrane
      potential and swelling in comparison to controls. These factors were
      significantly diminished by co-administration of Co-Q10 or LC compared to statin
      groups alone. Additionally, supplements caused a significant increase in serum
      insulin and succinate dehydrogenase activity. Our study provided new evidence
      supporting beneficial effects of Co-Q10 and LC on statin-induced pancreatic
      toxicity.

PMID- 29204173
TI  - Synthesis, characterization, cytotoxic screening, and density functional theory
      studies of new derivatives of quinazolin-4(3H)-one Schiff bases.
AB  - A series of novel derivatives of quinazolinone Schiff bases were synthesized from
      benzoic acid starting material and evaluated for potential cytotoxic activities
      against the human breast adenocarcinoma (MCF-7) and the human colon
      adenocarcinoma (HT-29) cell lines. Compared to the reference drug, these
      compounds showed good cytotoxic activities against studied cell lines especially
      compounds 4d and 4e. The ground-state geometries of these compounds (4a-g) were
      optimized at the B3LYP/6-31G* density functional theory (DFT) level. Then maximum
      absorptions electron affinity, ionization potential, electronegativity (chi),
      energy gap (Egap), hardness (eta), softness (S), electrophilicity (omega), and
      electrophilicity index (omegai) were calculated and discussed. The quantitative
      structure-activity relationship (QSAR) properties including the physicochemical
      parameters were also evaluated and studied. The computed properties of our novel
      synthesized compounds were compared with erlotinib compound.

PMID- 29204174
TI  - The silencing effect of miR-30a on ITGA4 gene expression in vitro: an approach
      for gene therapy.
AB  - Integrins are adhesion molecules which play crucial roles in cell-cell and cell
      extracellular matrix interactions. Very late antigen-4 or alpha4beta1 and
      lymphocyte Peyer's patch adhesion molecule-1 or alpha4beta7, are key factors in
      the invasion of tumor cells and metastasis. Based on the previous reports,
      integrin alpha4 (ITGA4) is overexpressed in some immune disorders and cancers.
      Thus, inhibition of ITGA4 could be a therapeutic strategy. In the present study,
      miR-30a was selected in order to suppress ITGA4 expression. The ITGA4 3' UTR was
      amplified, cloned in the Z2827-M67-(ITGA4) plasmid and named as Z2827-M67/3'UTR.
      HeLa cells were divided into five groups; (1) untreated without any transfection,
      (2) mock with Z2827-M67/3'UTR transfection and X-tremeGENE reagent, (3) negative
      control with Z2827-M67/3'UTR transfection alone, (4) test with miR-30a mimic and
      Z2827-M67/3'UTR transfection and (5) scramble with miR-30a scramble and Z2827
      M67/3'UTR transfection. The MTT assay was performed to evaluate cell survival and
      cytotoxicity in each group. Real-time RT-PCR was applied for the ITGA4 expression
      analysis. The findings of this study showed that miR-30a downregulated ITGA4
      expression and had no effect on the cell survival. Due to the silencing effect of
      miR-30a on the ITGA4 gene expression, this agent could be considered as a
      potential tool for cancer and immune disorders therapy.

PMID- 29204175
TI  - Preparation and in vitro characterization of retinoic acid-loaded poly(epsilon
      caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) micelles.
AB  - In order to achieve the controlled release of all-trans-retinoic acid (ATRA),
      poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL
      PEG-PCL) copolymer with average molecular weight of 5.34 kDa was synthesized. The
      nanosized micelles were prepared from copolymer by nano-precipitation method.
      Critical association concentration (CAC) of micelles was measured by fluorimetry
      and results indicated low CAC value of micelles (1.9 * 10-3 g/L). ATRA was
      encapsulated in the core of micelles using different ratios of drug to copolymer.
      In the case of 10% drug to polymer ratio, more than 80% of the drug was released
      within 3 days, whereas for ratio of 2% more than 90% of the drug was released
      within 3 h. The cytotoxic study performed by MTT assay showed that H1299 survival
      percent decreased significantly (P <= 0.05) after exposure to drug-loaded
      micelles, while no proliferation inhibition effect was observed by either free
      ATRA or blank PCL-PEG-PCL micelles.

PMID- 29204177
TI  - Anticlastogenic, radiation antagonistic, and anti-inflammatory activities of
      Persea americana in albino Wistar rat model.
AB  - The present study was undertaken to evaluate the anti-inflammatory activity and
      antigenotoxic effect of hydroalcoholic leaf extract of Persea americana (P.
      americana) in albino Wistar rats against whole body X-ray irradiation. Rats were
      orally administered with (25, 50, 100, 200, and 400 mg/kg body weight) of P.
      americana leaf extract for five days. On the fifth day after last administration,
      animals were exposed to whole body X-rays of 8 Gy. Based on Kaplan Meier's
      survival analysis, 100 mg/kg body weight was selected as an optimum dose for
      radioprotection. The radioprotective potential was analysed by bone marrow
      micronucleus test and comet assay in peripheral blood lymphocytes. Biochemical
      estimations were performed in liver tissue homogenates. DNA damage indicators
      analysed through comet assay displayed significant reduction in olive tail
      movement (P < 0.01), percentage DNA in tail (P < 0.05) and tail length (P <
      0.001) in pretreated group when compared to radiation group. P. americana leaf
      extract restored the levels of reduced glutathione, catalase, and reduced the
      levels of lipid peroxidation, protein carbonyls, and cyclooxygenase-2 levels in
      liver homogenates of pre-treated group. Decrease in micronucleated polychromatic
      erythrocytes (P < 0.05) was witnessed in P. americana pretreated group when
      compared to radiation control. Pretreatment also resulted in the increase of
      animal survival with dose reduction factor of 1.28. Our findings for the first
      time demonstrated that P. americana offers significant protection to rats from
      whole body exposure to X-rays and helps in antagonising the radiation effects,
      thereby combating acute radiation induced damage in living systems.

PMID- 29204176
TI  - Thymoquinone protects the rat kidneys against renal fibrosis.
AB  - Thymoquinone (TQ) is the main active ingredient of Nigella sativa seeds with
      various pharmacological effects. The aim of this study was to investigate the
      effect of TQ on renal fibrosis and permeability and oxidative stress status in
      lipopolysaccharide (LPS)-induced inflammation in male rats. Eighty male Wistar
      rats were divided into 5 groups as follow: control (received normal saline), LPS
      (1 mg/kg/day), and LPS+TQ (by doses of 2, 5 and 10 mg/kg/day). After three weeks,
      the biochemical parameters such as blood urea nitrogen (BUN) and creatinine in
      serum samples, oxidative stress markers including malondialdehyde (MDA), total
      thiol groups, superoxide dismutase (SOD) and catalase (CAT) activities in renal
      tissue homogenate and renal permeability (evaluated by Evan's blue dye method)
      were measured and renal fibrosis was evaluated, histologically using Masson's
      trichrome staining. LPS administration induced renal fibrosis (1.49 +/- 0.08 vs.
      7.15 +/- 0.18%) and significantly increased renal permeability (6.03 +/- 1.05 vs.
      13.5 +/- 1.04 MUg evans blue(EB)/g tissue), serum BUN and creatinine levels and
      oxidative stress marker (MDA) (P < 0.05), while, it reduced anti-oxidative
      markers including total thiol group, SOD and CAT activities (P < 0.05).
      Administration of TQ significantly improved these alterations which were dose
      dependent in oxidative stress markers, renal permeability (TQ 2, 5 and 10 mg/kg:
      10.7 +/- 0.3, 9.2 +/- 1.4 and 11.5 +/- 0.6 MUg EB/g tissue; respectively) and
      fibrosis (TQ 2, 5 and 10 mg/kg: 6.09 +/- 0.7, 4.26 +/- 0.14 and 2.52 +/- 0.08%;
      respectively). In conclusion, administration of TQ reduced renal fibrosis and
      permeability and improved oxidative stress status. Thus, TQ can be considered in
      conditions accompanied with chronic inflammation at least as a part of treatment
      strategy.

PMID- 29204178
TI  - Biological evaluation, docking and molecular dynamic simulation of some novel
      diaryl urea derivatives bearing quinoxalindione moiety.
AB  - In this study a series of diarylurea derivatives containing quinoxalindione group
      were biologically evaluated for their cytotoxic activities using MTT assay
      against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds
      were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram
      negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three
      Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria
      monocitogenes) and one yeast-like fungus (Candida albicans) strain. Furthermore,
      molecular docking was carried out to study the binding pattern of the compounds
      to the active site of B-RAF kinase (PDB code: 1UWH). Molecular dynamics
      simulation was performed on the best ligand (16e) to investigate the ligand
      binding dynamics in the physiological environment. Cytotoxic evaluation revealed
      the most prominent cytotoxicity for 6 compounds with IC50 values of 10-18 MUM
      against two mentioned cell lines. None of the synthesized compounds showed
      significant antimicrobial activity. The obtained results of the molecular docking
      study showed that all compounds fitted in the binding site of enzyme with binding
      energy range of -11.22 to -12.69 kcal/mol vs sorafenib binding energy -11.74
      kcal/mol as the lead compound. Molecular dynamic simulation indicated that the
      binding of ligand (16e) was stable in the active site of B-RAF during the
      simulation.

PMID- 29204179
TI  - Effects of Cornus mas fruit hydro-methanolic extract on serum antioxidants, lipid
      profile, and hematologic parameters following cisplatin-induced changes in rats.
AB  - Cisplatin (Cis) has serious adverse side-effects that limit its clinical use. The
      mechanism underlying the effects is complex, including mitochondrial oxidative
      stress and inflammation. This study investigated whether Cornus mas, a fruit with
      high antioxidant contents, hydro-methanolic extract (CME) can modulate the
      cisplatin-induced changes. Forty Wistar rats were divided into a control group,
      Cis group, CME group, CME 300 + Cis group, and the CME 700 + Cis group. After the
      intervention, blood samples were taken for biochemical and hematological
      analysis. CME analysis showed noticeable total phenol and total antioxidant
      contents. The plasma glutathione peroxidase and catalase levels were
      significantly decreased and malondialdehyde and blood hemoglobin levels were
      significantly increased in the Cis group, which were reversed to the control
      levels in the CME + Cis groups. In the CME group, the red blood cell count was
      significantly lower and the red cell distribution width and hemoglobin
      distribution width levels were significantly higher. In the Cis-treated group,
      white blood cells, neutrophils, monocytes, basophils, and large unstained cells
      were significantly increased and lymphocytes were significantly decreased when
      compared with the control group that was reached to non-significant levels in CME
      700 + Cis group. The blood cholesterol and high density lipoprotein in all CME
      treated groups were significantly decreased. The eosinophils increased in the CME
      group significantly. The results showed considerable total antioxidant and total
      phenol contents and relative protective effects of CME against Cis-induced
      antioxidant and hematologic changes in rats.

PMID- 29204181
TI  - Synthesis and evaluation of antimicrobial activity of cyclic imides derived from
      phthalic and succinic anhydrides.
AB  - Cyclic imides are a group of compounds which have valuable biological properties
      including cytotoxic, anti-inflammatory, antibacterial and antifungal activities.
      In this study, succinic and phthalic anhydrides were treated with glycinamide in
      pyridine to yield the corresponding amic acids. These amic acids underwent ring
      closure with acetic anhydride and anhydrous sodium acetate to form cyclic imides.
      In another procedure, succinic and phthalic anhydrides upon reaction with 2-amino
      benzylamine in pyridine gave the corresponding cyclic imides. The imides were
      screened for their antimicrobial activities against three types of bacteria and
      one type of fungi. Phthalimide derived from benzylamine exhibited remarkable
      antimicrobial activity against E. coli.

PMID- 29204180
TI  - Cytotoxic effects of the newly-developed chemotherapeutic agents 17-AAG in
      combination with oxaliplatin and capecitabine in colorectal cancer cell lines.
AB  - The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy
      geldanamycin (17-AAG) has been recently introduced as an attractive anticancer
      therapy. It has been shown that 17-AAG may potentiate the inhibitory effects of
      some classical anticolorectal cancer (CRC) agents. In this study, two panels of
      colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in
      combination with capecitabine and oxaliplatin as double and triple combination
      therapies on the proliferation of CRC cell lines. HT-29 and all HCT-116 cell
      lines were seeded in culture media in the presence of different doses of the
      mentioned drugs in single, double, and triple combinations. Water-soluble
      tetrazolium-1 (WST-1) assay was used to investigate cell proliferation 24 h after
      treatments. Then, dose-response curves were plotted using WST-1outputs, and IC50
      values were determined. For double and triple combinations respectively 0.5 *
      IC50 and 0.25 * IC50 were used. Data was analyzed with the software CompuSyn.
      Drug interactions were analyzed using Chou-Talalay method to calculate the
      combination index (CI).The data revealed that 17-AAG shows a potent synergistic
      interaction (CI < 1) with oxaliplatin and capecitabine in double combinations
      (0.5 * IC50) in both cell lines. In the case of triple combinations, the findings
      showed an antagonistic interaction (CI > 1) in HT-29 and a synergistic effect (CI
      < 1) in HCT-116 (0.25 * IC50) cell lines. It was concluded that double
      combinations of 17-AAG with oxaliplatin or capecitabine might be effective
      against HCT-116 and HT-29 cell lines. However, in triple combinations, positive
      results were seen only against HCT-116. Further investigation is suggested to
      confirm the effectiveness of these combinations in clinical trials.

PMID- 29204182
TI  - Baseline type 2 diabetes had a significant association with elevated high
      sensitivity cardiac troponin T levels in Chinese community-dwelling population: a
      5-year prospective analysis.
AB  - Background: The present analysis was designed to investigate the association of
      type 2 diabetes (T2D) with high sensitivity cardiac troponin T (hs-cTnT) during
      the 5 years of follow-up, and explore which one of fasting blood glucose (FBG)
      and postprandial blood glucose (PBG) is a determinant of this association in
      Chinese community-dwelling population. Methods: This prospective community-based
      analysis was conducted based on 730 participants without coronary artery disease
      and hs-cTnT values >=14 pg/mL receiving two measurements of hs-cTnT levels at
      baseline and follow-up of 5 years. Results: Prevalence of T2D was 16.2% (118
      participants). Median hs-cTnT levels were 4 (3-7) pg/mL and 6 (5-9) pg/mL at
      baseline and follow-up, respectively. The variation in hs-cTnT levels had a
      median of 2 (0-4) pg/ml (p < 0.001 for variation), and incidence of hs-cTnT
      levels >=14 pg/ml was 7.1% (52 participants) at follow-up. T2D had a significant
      association with elevated hs-cTnT levels in multivariate Logistic regression
      models (p < 0.05). Elevated levels of PBG (p < 0.05) rather than FBG (p > 0.05)
      determined the significant association with elevated hs-cTnT levels in
      multivariate linear regression models. Conclusions: This community-based analysis
      observed that there was a significant increment of hs-cTnT levels, and baseline
      T2D had a significant association with elevated hs-cTnT levels during the 5 years
      of follow-up. Moreover, the present analysis demonstrated that PBG rather than
      FBG played a crucial role in this association in Chinese community-dwelling
      population without CAD.

PMID- 29204183
TI  - Evaluation of outcomes for psychosis and epilepsy treatment delivered by primary
      health care workers in Nepal: a cohort study.
AB  - Background: Most evaluations of task-shifting have focused on common mental
      disorders. Much less work has been done on severe mental neurological and
      substance use (MNS) disorders, such as chronic psychosis and epilepsy. Given the
      high burden associated with severe MNS and the lack of mental health
      professionals in low and middle income countries, evaluations on the impact of
      task-shifting for these disorders are important. Methods: In a rural district of
      Nepal, a community mental health program, based on World Health Organization's
      Mental Health Gap Action Programme guidelines, was evaluated using a cohort study
      design. People with epilepsy and psychotic disorders were interviewed at
      treatment initiation and at 12-month follow-up. We also compared a group that was
      offered a comprehensive package of care (medication combined with psychosocial
      interventions, such as counselling and peer support groups) to a group that
      received medication only. Results: One-hundred nineteen persons were enrolled in
      the epilepsy cohort (EC) and 85 in the psychosis cohort (PC). The patients were
      enrolled in either the comprehensive package (n = 157) or medication only (n =
      47). There was significant improvement (P < 0.0001) in psychosis symptoms (PC: Z
      = 6.78, r = 0.80) and depressive symptoms (EC: Z = 7.43, r = 0.73; PC: Z = 6.02,
      r = 0.70), seizures (EC: Z = 6.78), functional disability (EC: Z = 6.38, r =
      0.67; PC: Z = 4.60, r = 0.57), family and caregiver burden (EC: Z = 8.09, r =
      0.85; PC: Z = 6.81, r = 0.84), and social behaviour (PC: Z = 5.94, r = 0.84).
      There was greater risk reduction for recent seizures among people with epilepsy
      in the comprehensive treatment package vs. medication only (risk ratio = 0.52,
      95% CI 0.29-0.95; P = 0.03); no other significant differences were observed
      between treatment arms. Conclusions: A community mental health program in Nepal,
      implemented by non-specialists, resulted in moderate to large effects among
      people with epilepsy or psychosis. A comprehensive package of care, including
      counselling and patient support groups, appears to offer added clinical benefits
      for patients with epilepsy. For people with psychosis, the basic package of care
      (i.e., psychotropic medications) performed similar to the comprehensive package,
      suggesting a less resource-intensive package may offer comparable results.

PMID- 29204184
TI  - Viral Cre-LoxP tools aid genome engineering in mammalian cells.
AB  - Background: Targeted nucleases have transformed genome editing technology,
      providing more efficient methods to make targeted changes in mammalian genome. In
      parallel, there is an increasing demand of Cre-LoxP technology for complex genome
      manipulation such as large deletion, addition, gene fusion and conditional
      removal of gene sequences at the target site. However, an efficient and easy-to
      use Cre-recombinase delivery system remains lacking. Results: We designed and
      constructed two sets of expression vectors for Cre-recombinase using two highly
      efficient viral systems, the integrative lentivirus and non-integrative adeno
      associated virus. We demonstrate the effectiveness of those methods in Cre
      delivery into stably-engineered HEK293 cells harboring LoxP-floxed red
      fluorescent protein (RFP) and puromycin (Puro) resistant reporters. The delivered
      Cre recombinase effectively excised the floxed RFP-Puro either directly or
      conditionally, therefore validating the function of these molecular tools. Given
      the convenient options of two selections markers, these viral-based systems offer
      a robust and easy-to-use tool for advanced genome editing, expanding complicated
      genome engineering to a variety of cell types and conditions. Conclusions: We
      have developed and functionally validated two viral-based Cre-recombinase
      delivery systems for efficient genome manipulation in various mammalian cells.
      The ease of gene delivery with the built-in reporters and inducible element
      enables live cell monitoring, drug selection and temporal knockout, broadening
      applications of genome editing.

PMID- 29204186
TI  - Percutaneous transesophageal gastro-tubing (PTEG) as an alternative long-term
      tube feeding procedure when gastrostomy is not feasible.
AB  - Background: Percutaneous transesophageal gastro-tubing (PTEG) is a minimally
      invasive technique to access the gut via an esophagostomy. However, this
      procedure is not well known and the literature available is still fairly limited.
      This observational study was conducted to evaluate our experience using this
      method as an alternative long-term tube feeding procedure when gastrostomy is not
      suitable. Methods: A total of 15 patients (10 males and 5 females) who underwent
      PTEG at our institution from 2012 to 2016 were observed and analyzed in this
      study. Results: The average age was 80.1 (71-93) years. Underlying conditions
      that required PTEG were previous gastric resection in 11 patients, left diaphragm
      disorder in 2 patients, interposing transverse colon between the abdominal wall
      and anterior gastric wall in 1 patient, and severe gastrostomy site leakage in 1
      patient. Tube placement was successful in all patients by approaching the left
      side of the neck, using a 15 Fr size tube. The mean postoperative length of stay
      was 22 (8-48) days. Postoperative adverse events included accidental tube
      dislodgement in three patients, tracheoesophageal fistula in one patient,
      inferior thyroid artery injury in one patient and thyroid gland mispuncture in
      one patient. There was no procedure-related mortality nor mortality at 30 days.
      Eight patients were discharged with some oral intake. Conclusions: PTEG is
      feasible in patients requiring long-term tube feeding for whom gastrostomy is
      unsuitable. It is an effective long-term tube feeding procedure and should be
      offered as a more comfortable alternative to nasogastric tubing.

PMID- 29204185
TI  - Bioengineering considerations in liver regenerative medicine.
AB  - Background: Liver disease contributes significantly to global disease burden and
      is associated with rising incidence and escalating costs. It is likely that
      innovative approaches, arising from the emerging field of liver regenerative
      medicine, will counter these trends. Main body: Liver regenerative medicine is a
      rapidly expanding field based on a rich history of basic investigations into the
      nature of liver structure, physiology, development, regeneration, and function.
      With a bioengineering perspective, we discuss all major subfields within liver
      regenerative medicine, focusing on the history, seminal publications, recent
      progress within these fields, and commercialization efforts. The areas reviewed
      include fundamental aspects of liver transplantation, liver regeneration, primary
      hepatocyte cell culture, bioartificial liver, hepatocyte transplantation and
      liver cell therapies, mouse liver repopulation, adult liver stem cell/progenitor
      cells, pluripotent stem cells, hepatic microdevices, and decellularized liver
      grafts. Conclusion: These studies highlight the creative directions of liver
      regenerative medicine, the collective efforts of scientists, engineers, and
      doctors, and the bright outlook for a wide range of approaches and applications
      which will impact patients with liver disease.

PMID- 29204188
TI  - Ultrahigh-speed endoscopic optical coherence tomography and angiography enables
      delineation of lateral margins of endoscopic mucosal resection: a case report.

PMID- 29204187
TI  - Use of beta-blockers and risk of serious upper gastrointestinal bleeding: a
      population-based case-control study.
AB  - Background: Some studies indicate a reduced risk of serious upper
      gastrointestinal bleeding (UGIB) for users of beta-blockers, but the association
      remains to be confirmed in larger studies and characterized with respect to
      differences among beta-blockers. We aimed to assess whether beta-blocker use
      decreases the risk of UGIB. Methods: We conducted a register-based, population
      based case-control study in Denmark. We identified cases with a first validated
      discharge diagnosis of UGIB during the period 1995-2006. Controls were selected
      by risk-set sampling in a ratio of 10:1. We estimated crude and adjusted odds
      ratios (ORs) of the association between current beta-blocker use and the risk of
      UGIB by using conditional logistic regression and further stratified by selective
      and non-selective beta-blockers, respectively. Results: We identified 3571 UGIB
      cases and 35,582 controls. Use of beta-blockers was not found to be associated
      with a decreased risk of UGIB (adjusted OR 1.10; 95% CI: 1.00-1.21). The
      association remained neutral after stratification by selective and non-selective
      beta-blockers, and by single beta-blocker substances. Similarly, we found no
      association between current beta-blocker use and the risk of UGIB within
      different subgroups. Conclusions: We found no association between beta-blocker
      use and UGIB.

PMID- 29204189
TI  - Reversible splenial lesion syndrome (RESLES) coinciding with cerebral venous
      thrombosis: a report of two cases.
AB  - A total of two postpartum women with no noteworthy medical history presented with
      persistent headache. Brain magnetic resonance imaging (MRI) of both revealed
      extensive cerebral venous thrombosis, concurrently with abnormal signals of the
      splenium of the corpus callosum (SCC): The splenium appeared hyperintense on T2
      weighted sequences, fluid-attenuated inversion recovery (FLAIR), and diffusion
      weighted imaging (DWI) imaging, and hypointense on T1 sequences and apparent
      diffusion coefficient (ADC) map. The patients were given thrombolytic therapy.
      Clinically, both patients achieved recovery with no neurologic sequelae, and
      follow-up MRI revealed complete resolution of the lesion in the SCC at day 36 and
      day 37 after initial presentation, respectively.

PMID- 29204190
TI  - Oral teriflunomide in the treatment of relapsing forms of multiple sclerosis:
      clinical evidence and long-term experience.
AB  - Key objectives in the treatment of multiple sclerosis (MS) include prevention of
      relapses, a reduction in the accumulation of disability and slowing of the brain
      volume loss that occurs from the earliest stages of the disease. Teriflunomide, a
      once-daily, oral immunomodulatory therapy, has demonstrated efficacy across
      multiple measures of disease activity and worsening in patients with relapsing
      forms of MS and in those with a first clinical episode suggestive of MS. In this
      review, the latest evidence relating to the proposed mechanism of action of
      teriflunomide in MS is explored, including novel insights provided from the
      recently completed Teri-DYNAMIC study. Key clinical and magnetic resonance
      imaging data from the completed long-term extensions of the phase II and III
      (TEMSO, TOWER and TOPIC) studies are highlighted, and the long-term safety
      profile of teriflunomide, as evidenced by data from these extension studies, is
      presented. Although randomized clinical trials represent the highest level of
      evidence to support the use of therapeutic interventions, it is also important to
      understand the performance of a particular treatment in the real-world setting.
      In this regard, the results of the recently completed, global, phase IV Teri-PRO
      study are of particular interest and provide further insights into the benefits
      of teriflunomide treatment from the patient perspective. Collectively, the data
      presented in this review demonstrate a favorable benefit-risk profile for
      teriflunomide, thereby supporting its long-term use for the treatment of patients
      with relapsing forms of MS.

PMID- 29204191
TI  - OnabotulinumtoxinA in the treatment of patients with chronic migraine: clinical
      evidence and experience.
AB  - Chronic migraine is a debilitating neurobiological disorder that affects
      approximately 1.4-2.2% of the population worldwide. Patients with chronic
      migraine have 15 or more headache days per month, with at least 8 days per month
      that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a
      standardized injection protocol, was approved by the US Food and Drug
      Administration in 2010 for the treatment of chronic migraine. The approval was
      made based on results from two large, randomized, double-blind placebo-controlled
      trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT)
      trials. Since then, numerous studies have been performed investigating the short
      term and long-term benefits, risks and complications of the use of
      onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose
      of this narrative review is to describe the currently available clinical evidence
      for the use of onabotulinumtoxinA injections for treating patients with chronic
      migraine.

PMID- 29204192
TI  - RASSF1A and SIRT6 in non-small cell lung cancer: Relationship with clinical
      outcome.
AB  - This study investigated the expression of RASSF1A and SIRT6 in non-small cell
      lung cancer (NSCLC) and its relationship with clinical prognosis. The expression
      in 122 cases of NSCLC tissues (NSCLC group) and 122 cases of normal lung tissues
      (NOR group) during the same period were detected by immunohistochemical Super Pic
      TureTM Polymer two-step method, and the relationship between its expression and
      the clinicopathological features and prognosis of patients was analyzed. The
      positive expression rates of RASSF1A and SIRT6 in NSCLC group were lower than
      those in the normal group (55.74 vs. 84.43% and 52.46 vs. 82.49%, P<0.01). The
      differences in expression intensity of RASSF1A in NSCLC tissues between different
      tumor pathological types, tumor differentiation degrees and lymph node metastases
      were statistically significant, and the differences in expression intensity of
      SIRT6 between different TNM stages, tumor differentiation degrees and lymph node
      metastases were statistically significant. There was a positive correlation
      between the expression of RASSF1A and SIRT6 in NSCLC group (r=0.532, P<0.01). The
      3-year survival rate of patients with high-expression of RASSF1A was higher than
      in those with low-expression of RASSF1A (81.33 vs. 39.45%, log-rank chi2=19,102,
      P<0.01); the 3-year survival rate of patients with high-expression of SIRT6 was
      higher than in those with low-expression of SIRT6 (83.51 vs. 42.43%, log-rank
      chi2=17,180, P<0.01). The low expression of RASSF1A and SIRT6 and lymph node
      metastasis were the risk factors affecting the prognosis of NSCLC patients. There
      is a better correlation between the expression of RASSF1A and SIRT6 in NSCLC
      tissues, and the detection of their expression is of great significance in the
      judgement of clinicopathological features and prognosis of NSCLC patients.

PMID- 29204193
TI  - Management and Outcome Analysis of Pediatric Unstable Thoracolumbar Spine Injury:
      Large Surgical Series with Literature Review.
AB  - Pediatric thoracolumbar spine fractures are considered rare injuries with paucity
      of publication across the globe. Further, spine injuries in children are
      comparatively rarer, and pediatric spine differs from adults, both
      biomechanically and anatomically; so, adult spine management strategy cannot be
      applied to pediatric cases, and exact guidelines for management of pediatric
      spinal injury is lacking. The current study is undertaken to study epidemiology,
      surgical management, and outcome of pediatric dorsolumbar unstable spine injury.
      A total of 25 pediatric patients were analyzed retrospectively with thoracic,
      thoracolumbar junction and lumbar spine injuries, who were managed surgically at
      our institute since June 2008, formed the cohort of the present study. There were
      19 males and six females with a mean age 14.8 years. Clinically, complete spinal
      cord injuries were observed in 11 (44%), and rest 14 had incomplete injury. Most
      common mode of injury was fall (76%) in contrast to the western countries and the
      thoracolumbar junction was the most common affected site. Among all patients who
      underwent surgical intervention, 68% cases had posterior decompression and
      pedicle screw fixation. Mean duration of hospital stay was 18 +/- 31 days. The
      mean follow-up period was 13.83 +/- 5.97 months. In incomplete neurological
      injury group, a total of 13 patients showed neurological improvement, out of
      which four cases improved by two Frankel grades, eight patients improved by at
      least 1 grade, and rest one by Grade 3 (Frankel Grade B to E). Neurological
      outcome was statistically significant in relation to the level of fracture (P -
      0.03) and preoperative Frankel grade, however, other factors, for example,
      gender, mode of injury, type of fracture, various surgical approaches with
      instrumentation, and correction of kyphotic deformity were found to be
      statistically nonsignificant. Surgical management of unstable pediatric
      dorsolumbar spine is a safe and an effective procedure which can provide good
      neurological outcome. The current study is one of largest series of cases managed
      surgically in this part of the world.

PMID- 29204195
TI  - Magnitude of Neurogenic Tumor Burden in Pediatric Population: A Tertiary Care
      Center Study.
AB  - Objective: Progress in the diagnosis and treatment of childhood neoplasm in the
      past few decades is one of the most gratifying achievements in the field of
      oncology. This study was aimed to ascertain the burden (incidence and prevalence)
      and histopathologic features of neurogenic tumors occurring in the pediatric
      population. Materials and Methods: The study evaluated a total of 492 cases of
      pediatric tumors over a period of 8 years from 2007 to 2015, including patients
      of 0-12 years of age group; attending the out-patients and in-patients Department
      of Pediatrics and Pediatric Surgery at Jawaharlal Nehru Medical College, AMU,
      Aligarh, with the complaints of tumor or tumor associated sign and symptoms.
      Clinical profile, hematological and histopathological examination along with
      immunohistochemical analysis were implicated to attain a conclusive diagnosis.
      Result: Out of 492 pediatric tumor cases, 255 (52%) cases were benign and 237
      (48%) cases were malignant. Neurogenic tumor (brain tumors) comprised 49 (10%) of
      the total case, being most common malignant solid neoplasm and second most common
      (next to leukemia) overall malignancy, constituting 49/237 (21%) cases.
      Astrocytoma 22/49 (45%) cases were the most common type brain tumor followed by
      medulloblastoma 15/49 (31%), ependymoma 9/49 (18%), and craniopharyngioma 3/49
      (6%). Conclusion: Effective management of pediatric neurogenic tumor is a
      multipronged approach involving effort of good Pediatric neurosurgeon,
      Pathologist and a host of Oncology specialists with insight into childhood
      neoplasms.

PMID- 29204196
TI  - Delineate, Yet not Dread: Anomalous Vertebral Artery in Pediatric Congenital
      Atlantoaxial Dislocation and Basilar Invagination.
AB  - Introduction: The deformed joints seen in congenital atlantoaxial dislocation
      (CAAD) are often associated with vascular anomalies. It is important to identify
      these vascular anomalies and address them appropriately without compromising the
      manipulation and fusion of C1-C2 joints. The small bones in pediatric age group
      pose an additional challenge. Materials and Methods: Data of fifty-six children
      with CAAD operated in the last 4 years was analyzed. A computed tomography
      angiogram was obtained preoperatively to assess for the course of the third
      segment of vertebral artery (VA). The anomalous VA was dissected and safeguarded
      during drilling and manipulation of the C1-C2 joints. Results: Of the 112 VAs, 5
      were aplastic, 21 crossed the joint posteriorly. Only one patient with reducible
      atlantoaxial dislocation (AAD) had anomalous VA crossing the joint posteriorly,
      the remaining VA anomalies were seen with irreducible AAD. Anomalous VA was seen
      on both sides in 2 patients. The most common anomaly was an inverted VA seen in
      seven sides. In all patients, the anomalous VA could be dissected and safeguarded
      without compromising the C1-C2 dissection and manipulation and fusion. In
      children, even the normal VA may occasionally pose difficulties while
      manipulation of joints. Challenges while addressing the anomalous and normal VA
      in pediatric age group have been described. Techniques to overcome these have
      been discussed. Conclusion: It is important to delineate the anomalous VA.
      However, the presence of such an artery is not a deterrent to the manipulation of
      C1-C2 joint, essential for best results. Special attention needs to be paid to
      the extent of distraction, medial C2 transverse foramen, and dissection/drilling
      of the area superior to the anomalous VA in the pediatric age group.

PMID- 29204197
TI  - Infantile Tremor Syndrome in Modern Times.
AB  - Background: Infantile tremor syndrome (ITS) is a clinical syndrome of acute or
      gradual onset of mental and psychomotor changes, pigmentary disturbances of hair
      and skin, pallor, and tremors in malnourished children aged between 5 months and
      3 years. It is a well-known entity, but the exact etiopathogenesis is still not
      known. Setting and Design: Prospective observational study carried out in the
      Department of Pediatrics at Dr RPGMC Tanda, Kangra in Himachal Pradesh. Materials
      and Methods: Demographic, clinical, and laboratory profile of 25 children with
      the diagnosis of preinfantile and ITS was collected who were admitted from May
      2014 to June 2015. Statistical Analysis: Descriptive analysis was performed using
      SPSS 17 trial version. Results: These children accounted for 0.5% of total
      pediatric admissions. Median, standard deviation age was 10, 3.1 months. Male to
      female ratio was 1.27:1. Cases were present throughout the year with two peaks
      observed in the months of May and November. This disease was found to be more
      common in higher birth order (68%). Complementary feeding, that too improper, was
      initiated in only 4 cases (16%). Ninety-six percent cases presented with comorbid
      illnesses. Respiratory tract infection was the most common association, followed
      by urinary tract infection. There was moderate anemia with dimorphic picture
      (40%). Thirteen (52%) had vitamin B12 levels below normal. Magnesium levels,
      though statistically insignificant (P = 0.8) were lower in patients with tremors.
      Conclusion: This is a disease of multi-micronutrient deficiency, which can be
      present either alone or in association. Educating women about proper nutrition
      during pregnancy and timely administration of complementary feeding is of utmost
      importance.

PMID- 29204194
TI  - Synaptogenesis in the Cerebellum of Offspring Born to Diabetic Mothers.
AB  - There is increasing evidence that maternal diabetes mellitus during the pregnancy
      is associated with a higher risk of neurodevelopmental and neurofunctional
      anomalies including motor dysfunctions, learning deficits, and behavioral
      problems in offspring. The cerebellum is a part of the brain that has long been
      recognized as a center of movement balance and motor coordination. Moreover,
      recent studies in humans and animals have also implicated the cerebellum in
      cognitive processing, sensory discrimination, attention, and learning and memory.
      Synaptogenesis is one of the most crucial events during the development of the
      central nervous system. Synaptophysin (SYP) is an integral membrane protein of
      synaptic vesicles and is considered to be a marker for synaptic density and
      synaptogenesis. Here, we review the manuscripts focusing on the negative impacts
      of maternal diabetes in pregnancy on the expression or localization of SYP in the
      developing cerebellar cortex. We believe that the alteration in synaptogenesis or
      synapse density may be part of the cascade of events through which diabetes in
      pregnant women affects the newborn's cerebellum.

PMID- 29204198
TI  - Profile and Outcome of Pediatric Brain Tumors - Experience from a Tertiary Care
      Pediatric Oncology Unit in South India.
AB  - Context: Tumors of the central nervous system (CNS) constitute the second most
      common pediatric cancers. Unlike leukemia, management of CNS tumors requires a
      good multidisciplinary team. Higher rates of treatment abandonment are documented
      in view of complexity of the treatment with long duration, involving
      neurosurgery, radiation, chemotherapy, and high cost of treatment. Morbidity
      associated with CNS tumors may be significant in terms of physical deficits as
      well as neuropsychological and neuroendocrine sequelae. Pediatric neurooncology
      is still at a very nascent stage in the developing countries. There are only a
      few reports on the multidisciplinary approach and outcomes of pediatric brain
      tumors in developing countries. Aims: The aim of this study is to identify the
      clinicopathological profile of Pediatric CNS tumors in a tertiary care center
      located in South India in comparison with reports from other low-and middle
      income Countries. Settings and Design: A retrospective analysis of medical
      records of all children diagnosed with brain tumors from January 2012 to November
      2016 at our institute was done. Subjects and Methods: A retrospective study of
      clinical, pathological profile, and outcomes of children <18 years diagnosed with
      brain tumors at our institute from January 2012 to November 2016 was done.
      Histopathological categorization was done as per the WHO classification 2007. The
      multidisciplinary treatment with respect to surgery, radiation, and chemotherapy
      was noted and the outcomes were recorded. Statistical Analysis Used: R for
      Statistical Computing (Version 3.0.2; 2013-09-25). Results: A total of 52
      children were diagnosed with male preponderance of 66.6%. Highest incidence was
      noted in the age group of 0-4 years (50%). Majority of them were supratentorial
      (59.6%). CNS embryonal tumors contributed to 48% of all our brain tumors. 73% of
      them underwent either resection or biopsy. Eight (15.3%) of them died due to the
      progression of disease, but 44% abandoned treatment due to the
      progression/recurrence of disease. Those lost to follow-up were mostly among the
      high-risk groups with poor prognosis such as pontine glioma, medulloblastoma
      (high risk), and primitive neuroectodermal tumor. Conclusions: Although brain
      tumors constituted 30% of all our solid tumors, only 56% of them received
      appropriate treatment and 25% abandoned treatment. High rates of abandonment were
      a consequence of late diagnosis, complex multidisciplinary treatment involved,
      high treatment cost, lack of uniformity in management between different oncology
      centers and poor prognosis of the tumor subtype.

PMID- 29204199
TI  - Clinicopathological Study of Pediatric Posterior Fossa Tumors.
AB  - Context: Brain tumor is one of the most devastating forms of human illness,
      especially when occurring in the posterior fossa and involving the brainstem.
      Tumors in the posterior fossa are considered some of the most critical brain
      lesions. This is primarily due to the limited space within the posterior fossa,
      as well as the potential involvement of the vital brainstem nuclei. Aims: The aim
      of this study is to analyze the incidence, clinical features, surgical outcome,
      complications, and prognosis in a series of 37 pediatric patients with posterior
      fossa tumors who underwent surgery between September 2012 and January 2015 from
      the Department of Neurosurgery, King George Hospital, Visakhapatnam (both
      prospective and retrospective study). Materials and Methods: A series of 37 cases
      were treated by the Department of Neurosurgery, King George Hospital, between
      August 2012 and January 2015. Results: Posterior fossa tumors are predominantly
      seen in children with a peak incidence in the first decade. The most common
      presenting symptoms are raised intracranial pressure with headache and vomiting.
      Majority of the tumors are medulloblastomas, ependymomas, and cerebellar
      astrocytomas. The most common location is the cerebellar vermis, followed by the
      cerebellar hemispheres, followed by the forth ventricle and then the brainstem.

PMID- 29204200
TI  - Quality of Life in Indian Children with Cerebral Palsy Using Cerebral Palsy
      quality of Life Questionnaire.
AB  - Background: Quality of life (QOL) in children with cerebral palsy (CP) needs to
      be measure by CP-specific questionnaire. CP-QOL questionnaire is being used for
      this purpose. Objectives: The aim is to determine the QOL in Indian children with
      CP using CP-QOL questionnaire and to correlate QOL scores with demographic
      details of the patient. Materials and Methods: Subjects were parents of 50
      children (4-12 years) attending child development center of Guru Teg Bahadur
      Hospital were enrolled. The parent-proxy version of the CP-QOL questionnaire
      translated into Hindi was administered by one author. Scoring and analysis were
      performed as per specified method. Cronbach's alpha was calculated for each
      domain for validation. Effect of clinical and demographic profile on QOL was
      analyzed. Results: CP-QOL questionnaire was administered to 50 parents of CP
      children (32 males, 18 females). The overall QOL score of the children studied
      was computed to be 38.29 +/- 5.2. Age and maternal education had a significant
      bearing on the QOL of the children (P < 0.05). Type of CP, gender, and epilepsy
      did not affect the QOL significantly (P > 0.05). Good internal consistency and
      reliability were found in the domains of social well-being and acceptance,
      functioning, participation, and physical health (Cronbach's alpha >0.7). Access
      to services, pain, and impact of disability and family health showed a weak
      correlation with Cronbach's alpha <0.7. Conclusion: QOL in children with CP was
      compromised. The CP-QOL questionnaire can be used to measure QOL in Indian
      children with CP.

PMID- 29204201
TI  - Health-related Quality of Life in Children with Congenital Hydrocephalus and the
      Parental Concern: An Analysis in a Developing Nation.
AB  - Purpose: To analyze quality of life of children operated for congenital
      hydrocephalus and the concern of parents in taking care of these children.
      Methods: Thirty patients who underwent ventriculo-peritoneal shunt were randomly
      selected with minimum gap of 1 year between surgery and study. Canadian validated
      questionnaire was used. Overall health score (OHS) and parental concern score
      (PCS) were correlated with gender, family type and number of surgeries. Results:
      Mean OHS was 159.43 which was summation of physical health (mean 45.76), social
      emotional (mean 80.03) and cognitive health scores (mean 33.66). Mean OHS was
      151.57 for males and 177.77 for females (p-value 0.233). Nuclear and joint
      families had mean OHS of 160.36 and 158.89 respectively (p-value 0.944). Those
      who underwent one surgery had mean OHS of 167.48 and PCS of 23.10 whereas mean
      OHS was 140.66 and PCS was 27.78 for those with multiple procedures. Mean PCS for
      males was 26.71 and for females was 19.33 (p-value 0.036 statistically
      significant). This was not statistically significant between nuclear (24.73) and
      joint families (24.26). Conclusions: Quality of life of survivors of
      hydrocephalus is reasonably good even in developing countries due to keen
      parental involvement irrespective of gender, family type and number of surgeries.

PMID- 29204202
TI  - Occult Disseminated Tuberculosis with Holocord Longitudinally Extensive
      Transverse Myelitis: A Rare Phenomenon in a Child.
AB  - Longitudinally extensive transverse myelitis (LETM) is defined as an inflammatory
      lesion of the spinal cord that extends to three or more segments. LETM is a
      commonly characteristic feature of neuromyelitis optica (NMO) or various
      autoimmune diseases. Manifestation of Mycobacterium tuberculosis (MTB) infection
      with LETM are rare and usually in the cervicothoracic spinal cord. Our patient
      presented with holocord LETM, so NMO was considered initially diagnosis. After in
      further research, MTB was diagnosed and treated successfully. The current case
      underscores that tuberculosis must be keep in mind when undertaking differential
      diagnosis of demyelinating diseases even in the absence of symptoms of infection,
      and especially in endemic regions.

PMID- 29204203
TI  - Intradiploic Pterional Epidermoid Tumor: A Case Report and Review of literature.
AB  - Intradiploic epidermoid cyst is an uncommonly occurring neoplasm, and only about
      200 cases are reported in the form of isolated case report. It is presumed to
      occur due to ectodermal cells in inclusion in the bone tissue during embryonic
      life neural tube closure. It commonly remains asymptomatic or rarely presents as
      a bony lump in the skull bone. Authors report present an interesting case, which
      presented with swelling, and underwent successful surgical resection. Pertinent
      literature along with diagnosis and management is briefly reviewed. These lesions
      can erode the bone and involve the brain parenchyma due to their proximity to the
      brain. Radiological imaging is very helpful in accurate diagnosis of these
      lesions and in differentiating intradural from intradiploic varieties of
      epidermoid. We present an unusual case of this pathology.

PMID- 29204204
TI  - Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially
      Treatable Cause of Leigh's Disease.
AB  - Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder
      that affects tissues with high energy demand such as the central nervous system.
      The clinico-radiological phenotype of Leigh's disease is one of its common
      presentations. We present a 9-month-old boy with rapidly progressive infantile
      Leigh's disease. PDHA1 gene sequencing revealed a pathological homozygous
      missense mutation c.131A>G or p.H44R in exon 3 consistent with PDHC deficiency.
      H44R is among the five mutations (H44R, R88S, G89S, R263G, and V389fs) in E1alpha
      subunit that is thiamine-responsive. The child was initiated on thiamine,
      riboflavin, carnitine, coenzyme Q, and sodium benzoate supplementation. Mild
      recovery was noted at 6 months follow up as no further episodes of encephalopathy
      occurred. Thereafter, the child was treated with Ketogenic diet which resulted in
      increased levels of activity and alertness. Despite an improving course, the
      child had a sudden unexpected death at the age of 21 months.

PMID- 29204205
TI  - A Giant Occipital Encephalocele in Neonate with Spontaneous Hemorrhage into the
      Encephalocele Sac: Surgical Management.
AB  - The presence of giant occipital encephalocele represents a surgical challenge.
      However, preoperative magnetic resonance imaging with venography can help in
      delineating relation of venous sinus, content of the sac and help classify
      occipital encephalocele into infra-torcular and torcular depending on the
      relation with position of torcula. However, the presence of old hemorrhage into
      encephalocele sac is extremely rare and in the detailed PubMed search, the
      authors could find one such case, reported by Nath et al. The author reports a
      case of giant occipital encephalocele; during surgery, evidence of old bleed was
      noted. Pertinent literature and management are reviewed briefly.

PMID- 29204206
TI  - Subaponeurotic Cerebrospinal Fluid Collection in an Infant.
AB  - Subaponeurotic cerebrospinal fluid (CSF) collection is a rare condition. We
      report a 13-week-old male infant who presented with a swelling in the
      occipitoparietal region of 4 h duration. Swelling was soft, fluctuant, and
      contained CSF. It was tapped twice on the 4th and 8th day of appearance and
      resolved completely by 7 weeks. The condition is benign, and a conservative
      approach is recommended.

PMID- 29204207
TI  - Primary Ewing's Sarcoma of Cranium in a Pediatric Patient.
AB  - Ewing's sarcoma primarily involving the skull is an unusual occurrence (1% of all
      Ewing's sarcoma cases) with very few reported cases in the published literature.
      The challenge in such cases is to establish a definitive diagnosis before
      starting the multidisciplinary treatment approach. We report such a rare case in
      a 13-year-old boy who is being treated at our institute with an intention of
      adding to the limited information we currently have on diagnosis, management, and
      the outcome of such cases.

PMID- 29204208
TI  - Pallister-Hall Syndrome.
AB  - Polydactyly is a relatively common abnormality in infants. However, it can be a
      marker of a wide variety of neurological and systemic abnormality. Hence, it is
      important for pediatrician and physician to have insight into the various
      association of this apparently innocuous anomaly. In this write-up, we report an
      extremely rare syndrome associated with polydactyly that is Pallister-Hall
      syndrome. A 10-month-old male child born by lower segment cesarean section
      presented with global delay associated with microcephaly, frontal bossing,
      hypertelorism, flat nose, short philtrum, incomplete cleft in the upper lip and
      hard palate, polydactyly, and syndactyly. The child presented with repeated
      vomiting and crying episodes. The patient was investigated which revealed a
      hypothalamic hamartomas. Pallister-Hall syndrome is a very rare autosomal
      dominant genetic disorder due to mutation in GLI3 gene in the short arm of
      chromosome 7 with variable penetrance and expressivity.

PMID- 29204209
TI  - Perinatal Rapid Enlargement of Suprasellar-Prepontine Arachnoid Cyst: Report of
      Case and Literature Review.
AB  - Arachnoid cysts are benign developmental anomalies representing 1% of all
      intracranial lesions. Suprasellar prepontine location of arachnoid cyst in the
      perinatal period has been reported in the perinatal period with the advent of
      prenatal imaging. A rare case of rapidly enlarging suprasellar prepontine
      arachnoid cyst diagnosed at 28 weeks on routine antenatal ultrasonographic and
      magnetic resonance imaging is presented. Rapid enlargement of the cyst near term
      led to endoscopic fenestration of the cyst and ventriculocystocisternostomy
      followed by ventriculoperitoneal shunt in the postnatal life. Serial imaging in
      the perinatal period led to early intervention with good postnatal outcome. We
      also review all cases of prenatal suprasellar prepontine arachnoid cyst mentioned
      in literature and discuss the management strategies.

PMID- 29204210
TI  - Spontaneous Umbilical CSF Fistula Due to Migration of the Peritoneal End of VP
      Shunt: A Case Report and Review of Pathogenesis.
AB  - Abdominal complications after ventriculoperitoneal (VP) shunt surgery for
      hydrocephalus have been known to occur. The more common complications include
      peritoneal pseudocyst, obstruction of the lower end, and shunt infection.
      Perforations of the intra-abdominal hollow viscera leading to spontaneous
      extrusions of the peritoneal catheter via the natural orifices have also been
      reported. A rarer phenomenon still is the migration of the lower end of the VP
      shunt through the anterior abdominal wall, leading to the formation of a
      spontaneous umbilical fistula at a site unrelated to the surgical site. Eight
      cases have been described in the literature so far with various causes
      elucidated. We report this condition in a child 4.5 years after his shunt surgery
      and postulate different mechanisms for both early and late presentations of this
      condition.

PMID- 29204211
TI  - Unusual Cause of West Syndrome.
AB  - Schimmelpenning-Feuerstein-Mims syndrome is a congenital neurocutaneous disorder,
      comprising of organoid epidermal nevus with a broad spectrum of multiorgan
      dysfunction (neurologic, skeletal, cardiovascular, ophthalmic, and urologic)
      secondary to postzygotic mutation in the early embryonic period. Predominant
      neurological manifestations include epilepsy, intellectual impairment, and focal
      deficits. Here, we report a 3-year-old girl who presented with epileptic spasms
      and had a characteristic linear sebaceous nevus. This report not only highlights
      the importance of early diagnosis of this condition but also emphasizes the need
      for multiorgan screening in children with seizures and nevi.

PMID- 29204213
TI  - Endolymphatic Sac Tumor in von Hippel-Lindau Disease: A Rare Case Report.
AB  - Endolymphatic sac tumor (ELST) is a rare papillary neoplasm with locally
      destructive behavior which can occur sporadically or in association with Von
      Hippel-Lindau (VHL) disease. We herein present a case of ELST associated with VHL
      disease in a 14-year-old girl and discuss clinico-radiological,
      immunohistopathologic findings, and management by staged surgery and
      postoperative radiotherapy to the residual lesion.

PMID- 29204212
TI  - Isolated Superior Divisional Oculomotor Nerve Palsy and Nystagmus Following Mild
      Trauma.
AB  - Traumatic isolated divisional oculomotor nerve palsy has not been reported
      following mild head injury. We present an interesting case of a 10-year-old male
      boy who presented with right-sided ptosis, upgaze palsy, and horizontal nystagmus
      following a mild head trauma. Magnetic resonance imaging showed right superior
      rectus muscle atrophy. After observing for 6 months, right inferior rectus
      recession was done. The abnormal head posture and diplopia got corrected, but
      nystagmus persisted, although with appreciably decreased amplitude. We here
      report a rare case of an isolated superior divisional oculomotor nerve palsy
      following mild head trauma. Nystagmus accompanying a divisional oculomotor nerve
      palsy has never been reported before, making this case more unique. A critical
      step-wise approach to the case with possible mechanisms are discussed.

PMID- 29204214
TI  - Magnetic Resonance Imaging of Pediatric Primary Cerebral Hydatidosis.

PMID- 29204215
TI  - Tribute to Grunya Efimovna Sukhareva, the Woman who First Described Infantile
      Autism.

PMID- 29204216
TI  - Neurodevelopmental Disorders between Past and Future.

PMID- 29204217
TI  - Parainfectious Ocular Flutter and Truncal Ataxia and Dengue.

PMID- 29204219
TI  - Validation of the EuroSCORE II in a Greek Cardiac Surgical Population: A
      Prospective Study.
AB  - Objective: The objective of this study was to examine the validity of EuroSCORE
      II in the Greek population. Methods: A prospective single-center study was
      performed during November 1, 2013 and November 5, 2016; 621 patients undergoing
      cardiac surgery were enrolled. The EuroSCORE II values and the actual mortality
      of the patients were recorded in a special database. Calibration of the model was
      evaluated with the Hosmer-Lemeshow goodness-of-fit test, and discrimination with
      the areas under the receiver operating characteristic (ROC) curve. Results: The
      observed in-hospital mortality rate was 3% (i.e. 18/621 patients). The median
      EuroSCORE II value was 1.3% (1st quartile: 0.86%, 3rd quartile: 2.46%), which
      indicates a low in-hospital mortality. Area under the ROC curve for EuroSCORE II
      was 0.85 (95% CI: 0.75-0.94), suggesting very good correct classification of the
      patients. Conclusion: The findings of the present work suggest that EuroSCORE II
      is a very good predictor of in-hospital mortality after cardiac surgery, in our
      population and, therefore can safely be used for quality assurance and risk
      assessment.

PMID- 29204218
TI  - Interpreting the Mechanism of APOE (p.Leu167del) Mutation in the Incidence of
      Familial Hypercholesterolemia; An In-silico Approach.
AB  - Background: Apolipoprotein E (APOE) gene is a ligand protein in humans which
      mediates the metabolism of cholesterol by binding to the low-density lipoprotein
      receptor (LDLR). P.Leu167del mutation in APOE gene was recently connected with
      Familial Hypercholesterolemia, a condition associated with premature
      cardiovascular disease. The consequences of this mutation on the protein
      structure and its receptor binding capacity remain largely unknown. Objective:
      The current study aims to further decipher the underlying mechanism of this
      mutation using advanced software-based algorithms. The consequences of disrupting
      the leucine zipper by this mutation was studied at the structural and functional
      level of the APOE protein. Methods: 3D protein modeling for both APOE and LDLR
      (wild types), along with APOE (p.Leu167del) mutant type were generated using
      homology modeling template-based alignment. Structural deviation analysis was
      performed to evaluate the spatial orientation and the stability of the mutant
      APOE structure. Molecular docking analysis simulating APOE-LDLR protein
      interaction was carried out, in order to evaluate the impact of the mutation on
      the binding affinity. Result: Structural deviation analysis for APOE mutated
      model showed low degree of deviance scoring root-mean-square deviation, (RMSD) =
      0.322 A. Whereas Docking simulation revealed an enhanced molecular interaction
      towards the LDLR with an estimation of +171.03 kJ/mol difference in binding free
      energy. Conclusion: This in-silico study suggests that p.Leu167del is causing the
      protein APOE to associate strongly with its receptor, LDLR. This gain-of-function
      is likely hindering the ability of LDLR to be effectively recycled back to the
      surface of the hepatocytes to clear cholesterol from the circulation therefore
      leading to FH.

PMID- 29204220
TI  - Impact of Post-Exodontia Bleeding in Cardiovascular Patients: A New
      Classification Proposal.
AB  - Background: Exodontia (dental extraction), being the most frequent minor surgical
      procedure in the general population, inevitably involves a large number of
      patients on antithrombotic medication. Current experience shows that there is a
      degree of confusion in managing these patients. Description: Post-exodontia
      bleeding, a natural consequence of every dental extraction with no or minor
      clinical significance in the vast majority of cases, often appears to be of major
      concern to both patients and healthcare practitioners (dentists or physicians),
      either because of the alarming nature of oral bleeding itself or because of the
      distorted perception about its importance. These concerns are enhanced by the
      lack of a universal standardized definition of post-exodontia bleeding and by the
      fact that all currently available post-exodontia bleeding definitions bear
      intrinsic limitations and tend to overestimate its clinical significance.
      Conclusion: In order to overcome the aforementioned issues, this article presents
      an overview of post-extraction bleeding and proposes a classification, based on
      the well-recognized Bleeding Academic Research Consortium (BARC) bleeding
      definition, aiming at reducing heterogeneity in this field.

PMID- 29204221
TI  - Antibiotic Resistance Patterns and Virulence Determinants of Different SCCmec and
      Pulsotypes of Staphylococcus Aureus Isolated from a Major Hospital in Ilam, Iran.
AB  - Aims & Objectives: The aim of this study is to evaluate genetic relatedness,
      antibiotic resistance pattern, and virulence characteristics of different types
      of S. aureus isolated from air, surfaces, staff, and patients in a Public
      hospital in Ilam. Methods & Materials: A total of 88 of 140 staphylococci
      identified as S. aureus by conventional and molecular methods were used in this
      study. Isolate samples were obtained from surfaces, staff, patients, and hospital
      indoor air. The sampling from staff and surfaces was done through using swab and
      air by standard pump. Antimicrobial susceptibility testing and presence different
      resistant and virulence determinants was assessed. Isolates were then typed by
      pulsed-field gel electrophoresis (PFGE) and SCCmec typing methods. Results: Out
      of 88isolates, 36 of them (40.9%) were MRSA. Among MRSA isolates, the range of
      resistance to antibiotic was 0% in vancomycin to 83.3% in gentamycin. The most
      prevalent resistant genes among gentamicin resistant S. aureus were acc (6')/aph
      (2")Ia and aph(3")IIIa. The most common erythromycin resistant gene was ermC.
      Surprisingly, SCCmec types I (30.5%), II (25%)were highly distributed. PFGE
      analysis showed 33 different pulsotypes. Conclusion: This study confirms that
      different isolates of MSSA and MRSA circulate in Ilam which differ in
      antimicrobial susceptibility, content of resistance, and virulence determinants.

PMID- 29204223
TI  - Arbuscular Mycorrhizal Fungi Increase the Phenolic Compounds Concentration in the
      Bark of the Stem of Libidibia Ferrea in Field Conditions.
AB  - Background: Libidibia ferrea is a species particular to the caatinga presenting
      medicinal properties for containing bioactive compounds. The use of Arbuscular
      Mycorrhizal Fungi (AMF) can increase the production of biomolecules in the legume
      leaves; however, no light has been shed on the role of symbiosis in maximizing
      metabolites production in the bark of L. ferrea stem. Objective: The aim was to
      select AMF that are efficient at increasing the production of phenolic compounds
      with medicinal properties in the bark of the L. ferrea stem. Methods: The
      experiment was designed in randomized blocks with four inoculation treatments
      (plants pre-inoculated with Claroideoglomus etunicatum, with Gigaspora albida,
      with Acaulospora longula, and non-inoculated plants - control) with six
      repetitions. Thirteen months after the transplanting, the plants were pruned and
      the bark of the stem was collected; subsequently, this plant material was dried
      in a chamber. After the drying process, fractions of the bark of the stem were
      macerated in methanol. The extracts were further used for analyses of the
      biomolecules. Results: The flavonoids concentration had an increase of,
      respectively, 236% and 186% in relation to the control for the treatments with A.
      longula and C. etunicatum; plants inoculated with A. longula had an increase of
      47% in total tannins concentration compared with the non-inoculated control - a
      benefit that the proanthocyanidins did not present. Conclusion: Applying
      inoculation with A. longula may be an alternative to increase the production of
      biomolecules of the secondary metabolism in the bark of the L. ferrea stem in
      field conditions.

PMID- 29204224
TI  - Bacteriology and Antibiogram of Urinary Tract Infection Among Female Patients in
      a Tertiary Health Facility in South Eastern Nigeria.
AB  - Background: Urinary Tract Infection (UTI) is a common contagion among men and
      women with the incidence relatively higher among women due to their differing
      anatomy. An understanding of the kind of pathogens implicated in urinary tract
      infections as well as antibiotic susceptibility profiling may help the clinician
      make rationally correct empirical choice in their treatment. Objective: This
      study is aimed at determining the type and antibiotic susceptibility pattern of
      bacterial uropathogens isolated from female patients attending Chukwuemeka
      Odumegwu Ojukwu University Teaching Hospital (COOUTH), Awka, Nigeria. Method: Two
      hundred and forty patients with clinically diagnosed UTI and who were on at least
      5 days' antibiotic holiday were recruited into the study. Their demographic
      characteristics were captured using pre-tested questionnaire. Their clean catch
      mid-stream urine samples were collected using sterile universal container and
      sent to the Microbiology Department for processing. Within 30 minutes of samples
      collection, the specimens were cultured and the isolates were identified, after
      24 h of incubation, using standard microbiological techniques. Antibiotic
      susceptibility tests were done with standard antibiotic discs using the Kirby
      bauer disc diffusion method. Results: Out of the 240 urine samples, 89.17%
      yielded significant bacteriuria. The pathogens implicated were Escherichia coli
      (28.5%), Staphylococcus aureus (28.0%), Salmonella spp (22.8%) and Pseudomonas
      aeruginosa (20.5%). HIV status, patients age, pregnancy status and marital status
      all significantly affected bacteriuria rate (p value < 0.05), while patients'
      location (sub-urban/rural dwelling), and level of education did not (p value >
      0.05). The pattern of microbial resistance to antibiotics suggests that
      ceftazidime, fosfomycin and cefoxitin may not be used as first-line agents in the
      empirical treatment of UTIs rather; levofloxacin, meropenem or aztreonam should
      be considered. Levofloxacin was significantly effective against all the isolates
      and may be administered empirically while waiting for the culture result (Mean %
      susceptibility was 79.85). Conclusion: E. coli and S. aureus were the predominant
      pathogens in the study and many were resistant to the commonly prescribed
      antibiotics and so leave the clinicians with only few alternative drugs for UTIs
      treatment. Routine surveillance and monitoring studies need to be constantly
      conducted to update clinicians on the prevalent pathogens and the rational and
      empirical treatment of UTIs. Aggressive and consistent health education using
      every possible media is also recommended to combat the menace of drug resistance
      occasioned by inappropriate antibiotic use.

PMID- 29204225
TI  - (in vivo Gastrocnemius Muscle) Tendon Ratio in Patients with Cerebral Palsy.
AB  - Background: The position of the gastrocnemius tendon in relation to the leg
      length may be different in children with cerebral palsy as compared to normal
      children. The palpation of muscle bellies or previous experience of the operating
      surgeon is employed to place the surgical incision for lengthening of the
      gastrocnemius aponeurosis. Inaccurate localisation may cause incorrect incisions
      and a risk of iatrogenic damage to the vital structures (i.e. sural nerve).
      Objectives: The aim of our study is to compare gastrocnemius length in-vivo
      between paretic and unaffected children and create a formula to localise the
      muscle-tendon junction accurately. Methods: 10 children with di/hemiplegia (range
      2-14y) were recruited. None of them had received any conventional medical
      treatment. An equal number of age/sex matched, typically developing children
      (range 4-14y) were recruited. Ultrasound scanning of the gastrocnemius muscle at
      rest was performed to measure the length of gastrocnemius bellies. We also
      measured the heights and leg lengths in all the children. Results: The
      gastrocnemius medial muscles were shorter in Cerebral Palsy children when
      compared to similar aged normal children. In cerebral palsy children, the
      gastrocnemius muscle and leg ratio ranged between 35 to 50% (average ratio of
      45%). Conclusion: Using these figures, we created an average percentage for
      gastrocnemius muscle length that may be used clinically to identify the tendon
      for open/endoscopic lengthening and also to make simple and accurate localisation
      of gastrocnemius muscle-tendon junction for surgical access. This decreases the
      length of the surgical incision and may reduce the risk of iatrogenic injuries.

PMID- 29204226
TI  - Information Security Risk Assessment in Hospitals.
AB  - Background: To date, many efforts have been made to classify information security
      threats, especially in the healthcare area. However, there are still many unknown
      risks which may threat the security of health information and their resources
      especially in the hospitals. Objective: The aim of this study was to assess the
      risks threatening information security in the hospitals located in one of the
      northwest cities of Iran. Method: This study was completed in 2014. The
      participants were information technology managers who worked in the hospitals
      (n=27). The research instrument was a questionnaire composed of a number of open
      and closed questions. The content validity of the questionnaire was confirmed,
      and the reliability of the closed questions was measured by using the test-retest
      method (r =0.78). Results: The results showed that among the information security
      risks, fire found to be a high probability/high impact risk factor. Human and
      physical/environmental threats were among the low probability risk factors.
      Regarding the information security safeguards used in the hospitals, the results
      showed that the use of the technical safeguards was the most frequent one (n =22,
      91.7%) compared to the administrative (n =21, 87.5%) and the physical safeguards
      (n =16, 66.7%). Conclusion: The high probability risk factors require quick
      corrective actions to be taken. Therefore, the underlying causes of such threats
      should be identified and controlled before experiencing adverse effects. It is
      also important to note that information security in health care systems needs to
      be considered at a macro level with respect to the national interests and
      policies.

PMID- 29204227
TI  - Workflow of CAD / CAM Scoliosis Brace Adjustment in Preparation Using 3D
      Printing.
AB  - Background: High correction bracing is the most effective conservative treatment
      for patients with scoliosis during growth. Still today braces for the treatment
      of scoliosis are made by casting patients while computer aided design (CAD) and
      computer aided manufacturing (CAM) is available with all possibilities to
      standardize pattern specific brace treatment and improve wearing comfort.
      Objective: CAD / CAM brace production mainly relies on carving a polyurethane
      foam model which is the basis for vacuuming a polyethylene (PE) or polypropylene
      (PP) brace. Purpose of this short communication is to describe the workflow
      currently used and to outline future requirements with respect to 3D printing
      technology. Method: Description of the steps of virtual brace adjustment as
      available today are content of this paper as well as an outline of the great
      potential there is for the future 3D printing technology. Results: For 3D
      printing of scoliosis braces it is necessary to establish easy to use software
      plug-ins in order to allow adding 3D printing technology to the current workflow
      of virtual CAD / CAM brace adjustment. Textures and structures can be added to
      the brace models at certain well defined locations offering the potential of more
      wearing comfort without losing in-brace correction. Conclusions: Advances have to
      be made in the field of CAD / CAM software tools with respect to design and
      generation of individually structured brace models based on currently well
      established and standardized scoliosis brace libraries.

PMID- 29204222
TI  - Paracoccidioidomycosis: Current Perspectives from Brazil.
AB  - Background: This review article summarizes and updates the knowledge on
      paracoccidioidomycosis. P lutzii and the cryptic species of P. brasiliensis and
      their geographical distribution in Latin America, explaining the difficulties
      observed in the serological diagnosis. Objectives: Emphasis has been placed on
      some genetic factors as predisposing condition for paracoccidioidomycosis.
      Veterinary aspects were focused, showing the wide distribution of infection among
      animals. The cell-mediated immunity was better characterized, incorporating the
      recent findings. Methods: Serological methods for diagnosis were also compared
      for their parameters of accuracy, including the analysis of relapse. Results:
      Clinical forms have been better classified in order to include the pictures less
      frequently observesiod. Conclusion: Itraconazole and the trimethoprim
      sulfamethoxazole combination was compared regarding efficacy, effectiveness and
      safety, demonstrating that azole should be the first choice in the treatment of
      paracoccidioidomycosis.

PMID- 29204228
TI  - Evaluation of Effective Dashboards: Key Concepts and Criteria.
AB  - Objective: The aim of this study is to offer appropriate criteria to evaluate
      effective dashboards for healthcare organizations. Method: In a Delphi study, a
      team of information technology consultants were asked to determine a set of user
      interface requirements for evaluating, building or selecting the dashboard. In
      the first round, a list of main features or criteria to be used was determined
      based on the panel's rating,. Results: In this study, it was revealed that a set
      of key criteria for evaluating the dashboards can be used for all types of
      dashboards. These criteria were classified into 7 main categories including user
      customization, knowledge discovery, security, information delivery, alerting,
      visual design, and integration and system connectivity. Conclusion: Choosing good
      criteria for selecting effective dashboards for healthcare organizations is very
      critical because these organizations follow a data-intensive and technology
      driven environment. This study revealed the importance of key criteria which can
      guarantee development of an evaluation checklist.

PMID- 29204229
TI  - Assessment of Primary Health Care in the Treatment of Tuberculosis in a Brazilian
      Locality of the International Triple Frontier.
AB  - Objective: To evaluate the performance of Primary Health Care (PHC) in treatment
      of TB patients in a triple international border municipality. Methods: The
      present study was an evaluative survey of cross-sectional and quantitative
      approach conducted with 225 PHC healthcare professionals. Data was collected
      through a structured and validated instrument, which provided five indicators of
      "structure" and four indicators of "process" classified as unsatisfactory,
      regular or satisfactory. Results: The "structure" component was unsatisfactory
      for the indicator of professionals involved in TB care and training, and regular
      for the indicator of connection between the units and other levels of care. The
      "process" component was regular for the indicators of TB information, directly
      observed treatment and reference and counter reference on TB, and unsatisfactory
      for external actions on TB control. Conclusion: The "structure" and "process"
      components points out some weaknesses in terms of management and organization of
      human resources. Low frequency of training and the turnover influenced the
      involvement of professionals. Elements of "structure" and "process" show the need
      for investing in the PHC team and improving the clinical management of cases.

PMID- 29204230
TI  - Validation of equations for pleural effusion volume estimation by
      ultrasonography.
AB  - Purpose: To validate the accuracy of previously published equations that estimate
      pleural effusion volume using ultrasonography. Methods: Only equations using
      simple measurements were tested. Three measurements were taken at the posterior
      axillary line for each case with effusion: lateral height of effusion (H),
      distance between collapsed lung and chest wall (C) and distance between lung and
      diaphragm (D). Cases whose effusion was aspirated to dryness were included and
      drained volume was recorded. Intra-class correlation coefficient (ICC) was used
      to determine the predictive accuracy of five equations against the actual volume
      of aspirated effusion. Results: 46 cases with effusion were included. The most
      accurate equation in predicting effusion volume was (H + D) * 70 (ICC 0.83). The
      simplest and yet accurate equation was H * 100 (ICC 0.79). Conclusion: Pleural
      effusion height measured by ultrasonography gives a reasonable estimate of
      effusion volume. Incorporating distance between lung base and diaphragm into
      estimation improves accuracy from 79% with the first method to 83% with the
      latter.

PMID- 29204231
TI  - Real-time elastography for the detection of fibrotic and inflammatory tissue in
      patients with stricturing Crohn's disease.
AB  - Purpose: The distinction between active inflammation and fibrosis of the bowel
      wall is essential for therapeutic decisions in stricturing Crohn's disease. We
      aimed to assess whether real-time elastography (RTE) with strain ratio
      measurement could be useful in differentiating fibrotic from inflamed bowel
      strictures and to evaluate the possible relationship between US techniques and
      the histology of the stenotic bowel wall. Materials and methods: Bowel
      ultrasonography (including RTE, color-Doppler and CEUS examination) was
      prospectively evaluated in 26 patients with symptomatic stricturing Crohn's
      disease, before surgery. RTE was adopted to evaluate bowel stiffness: five loops
      of 20 RTE frames were recorded for each stenotic segment and the mean strain
      ratio (MSR) was obtained. Histology scoring systems both for inflammation and
      fibrosis were established for surgical specimens. Results: No significant
      correlation was found between MSR and fibrosis score (P = 0.877). Color-Doppler
      score was significantly related to gut wall and submucosal thicknesses (P = 0.006
      and P = 0.032, respectively). There was no significant correlation between the
      number of vessels counted at histology and color-Doppler and CEUS examinations (P
      = 0.170 and P = 0.302, respectively). Conclusion: MSR detection was not able to
      distinguish fibrotic from inflammatory tissue in our selected population. This
      result could be influenced by the presence of the superimposed inflammation.
      Larger cohort of patients, further analysis with shear wave elastography, and
      validated histopathology classification systems for fibrosis and inflammation are
      necessary to assess if intestinal fibrosis could be reliably detected on the
      basis of bowel elastic properties.

PMID- 29204232
TI  - Vascular ultrasound in pediatrics: estimation of depth and diameter of jugular
      and femoral vessels.
AB  - Objectives: To estimate, on the basis of anthropometric and demographic
      variables, the depth (Dp) and diameter (Dm) of femoral and jugular vessels, which
      have been located and measured by ultrasound, in pediatric patients. Method: 750
      measurements of Dp and Dm of the femoral vein (FV), femoral artery (FA) and
      internal jugular vein (IJV) were made in 125 pediatric patients. The values were
      correlated with patients' sex, weight, age, size and body surface area (BSA).
      Results: Mean Dp values were 0.72 (0.34) cm for FA, 0.79 (0.35) cm for FV and
      0.77 (0.24) cm for IJV. Mean antero-posterior Dm values were 0.37 (0.17) cm for
      FA, 0.42 (0.22) cm for FV and 0.59 (0.23) cm for IJV. In the studied pediatric
      patients, femoral and jugular vessels depth correlated with age, size, weight and
      BSA (R = 0.46-0.60); vascular depth could be estimated from patients' weight and
      size (FA-Dp: R = 0.71; FV-Dp: R = 0.72; IJV-Dp: R = 0.53). Correlation with
      diameter was better for FA and FV (R = 0.81-0.89) than for IJV (R = 0.42-0.51);
      vascular diameter could be estimated from patient's size (FA-Dm: R = 0.89; FV-Dm:
      R = 0.86; IJV-Dm: R = 0.52). Conclusions: FV, FA and IJV depth and diameter
      correlated with weight, size, age and body surface area in the studied pediatric
      patients. Correlation was better for femoral than for jugular vessels. Depth
      could be estimated from patients' weight and size, while diameter could be
      estimated from the size. Such estimations may facilitate the choice of vessels to
      be cannulated, length and diameter of cannulation needles and the diameter of
      catheters to be used in pediatric patients.

PMID- 29204233
TI  - Median nerve evaluation by shear wave elastosonography: impact of "bone
      proximity" hardening artifacts and inter-observer agreement.
AB  - Purpose: Peripheral nerves frequently travel close to the bone surface and are,
      therefore, prone to elastosonographic "bone-proximity" hardening artifacts. The
      impact of these artifacts on quantitative measurements of median nerve stiffness
      performed by shear wave elastosonography has not been explored. Our aim was to
      assess normal median nerve stiffness values at various locations. Materials and
      methods: Thirty-six healthy volunteers (24 women and 12 men) aged between 25 and
      40 years were evaluated. Two operators performed the evaluation: one expert (6
      years of ultrasound experience) and one inexperienced operator (6 months'
      experience). The nerve was sampled in cross-section at three different locations:
      mid-forearm, immediately before the carpal tunnel and within the tunnel. The
      ultrasound scanner was equipped with a 14-MHz linear probe. The Shear Wave module
      was activated in one-shot mode. Measurements were performed using a ROI
      corresponding to the diameter of the nerve. Results: The mean values of stiffness
      of the medial nerve were 32.26 kPa +/- 18.60 within the carpal tunnel, 22.20 kPa
      +/- 9.84 at the carpal tunnel inlet and 7.62 kPa +/- 7.38 in the forearm. Inter
      observer agreement assessed using the intraclass correlation coefficient (ICC)
      was "moderate" within the carpal tunnel (ICC = 0.44), "moderate" at the carpal
      tunnel inlet (ICC = 0.41) and "fair" in the forearm (ICC = 0.38). Conclusions:
      The stiffness of the median nerve progressively increases in its distal portions,
      where the nerve approaches the bone surface. Inter-observer agreement was
      generally good (from fair to moderate).

PMID- 29204234
TI  - Carotid Doppler ultrasonography as a screening tool of early atherosclerotic
      changes in children and young adults with beta-thalassemia major.
AB  - Purpose: beta-thalassemia major (beta-TM) patients had an increased incidence of
      cardiovascular complications secondary to iron overload. They showed early
      carotid atherosclerosis as showed by increased carotid intima media thickness
      (CIMT) that may occur early even when significant iron overload is absent. We
      aimed to test the diagnostic performance of CIMT measurement by Doppler
      ultrasonography as a structural indicator for premature atherosclerosis in beta
      TM patients. Methods: Case-control study included 42 beta-TM patients (24 males
      and 18 females) aged from 3 to 30 years and 36 age- and sex-matched healthy
      controls. Carotid Duplex was used for measurement of CIMT in all subjects.
      Results: The frequency of abnormal CIMT among patients was 19%. Mean CIMT of
      right anterior wall was 0.8 +/- 0.16 (range 0.5-1.2) mm, of right posterior wall
      was 0.80 +/- 0.17 (range 0.5-1.2), of right lateral wall was 0.8 +/- 0.17 (range
      0.5-1.1) mm. CIMT of left anterior wall ranged from 0.5 to 1.2 with mean 0.81 +/-
      0.17, CIMT of left posterior wall ranged from 0.5 to 1.1 with mean 0.80 +/- 0.17
      mm. Mean CIMT of left lateral wall was 0.81 +/- 0.18 mm (range 0.5-1.2). CIMT of
      right anterior, right posterior and left anterior walls were thicker in patients
      compared to controls (P = 0.003, 0.015, < 0.001, respectively). There was no
      observable difference in CIMT between males and females, splenectomised and non
      splenectomised, or well and poorly chelated subgroups (P > 0.05). CIMT of right
      lateral wall correlated with the disease duration (r = 0.3, P = 0.04).
      Conclusions: Carotid ultrasound was a useful tool to detect subclinical
      atherosclerosis thorough CIMT evaluation in B-thalassemia major patients. B
      thalassemia major children proved to have an increased CIMT regardless the state
      of iron overload.

PMID- 29204235
TI  - Contrast-enhanced ultrasonography in clinical practice in Crohn's disease:
      feasibility of destruction/replenishment method and software analysis.
AB  - The aim of this Pictorial Essay is to evaluate the feasibility in the clinical
      practice of CEUS destruction/replenishment method and time intensity curve (TIC)
      analysis using the available software in patients with Crohn's disease. The
      ultrasound (US) procedure using contrast agent is briefly described, elaboration
      and analysis of the US sequences are explained in detail, and some advantages and
      disadvantages of the method are highlighted. The Authors suggest that the
      destruction/replenishment method is useful and time-saving in Crohn's disease if
      multiple measurements are required on intestinal portions adjacent to each other
      or in different locations.

PMID- 29204236
TI  - Hydatid cyst presented as a subcutaneous thigh mass.
AB  - Hydatid disease is an endemic zoonosis, and patients are generally from cattle-
      and sheep-raising regions of the world, such as Central Europe, the
      Mediterranean, the Middle East, China, South America, Australia, New Zealand,
      South Africa, and Russia (Lewall and McCorkell in Radiology 155:773-775, 1985).
      Furthermore, hydatid cyst is a disease of immigrants in non-endemic countries and
      in developed countries (Stojkovic et al. in PLoS Negl Trop Dis 6:e1880, 2012).
      The most common affected organs are liver and lungs. Hydatid cyst located in the
      subcutaneous tissue constitutes an extremely rare manifestation of the hydatid
      disease (Savulescu et al. in Chir Buchar Rom 1990 105:419-422, 2010). In this
      study, we report an uncommon case of hydatid cyst that developed in the
      subcutaneous tissue of the right thigh of a patient with ultrasound, computed
      tomography, and magnetic resonance imaging findings.

PMID- 29204238
TI  - Crossed fused renal ectopia: case report and review of the literature.
AB  - Crossed fused renal ectopia is a rare congenital anomaly, and is mostly detected
      incidentally. A 45-year-old man, during investigation for recurrent abdominal
      pain, was found to have an empty left renal fossa and right crossed renal ectopia
      with fusion on ultrasonography. In the present case, there were no abnormalities
      and/or alteration of the renal function. Abdominal tomography scan with contrast
      medium confirmed the diagnosis. Ectopic kidney is often associated with other
      abnormal situations such as agenesis, vascular malformation, incontinence, a
      palpable abdominal mass, urinary tract infection, high incidence of stone
      formation, and genital anomalies. Through this case report, we emphasize the
      importance of adequate imaging.

PMID- 29204237
TI  - Pediatric adrenal trauma: evaluation and follow-up with contrast-enhanced
      ultrasound (CEUS).
AB  - Adrenal trauma is rarely encountered in the pediatric population, often as a
      component of multi-organ injury and often presenting with hematoma formation.
      Contrast-enhanced computed tomography (CECT) is the established imaging modality
      both for initial evaluation and follow-up of patients with blunt abdominal
      trauma. In children, radiation exposure should be minimized and alternative
      imaging strategies are needed. Contrast-enhanced ultrasound (CEUS) has recently
      been successfully used for evaluation of patients with hepatic, renal and splenic
      injury. We present three cases of children with post-traumatic adrenal hematomas,
      which were initially diagnosed with CECT and subsequently followed up with CEUS,
      suggesting that CEUS may be considered for follow-up of adrenal injuries in
      children. CEUS improves the diagnostic capabilities by increasing tissue contrast
      and spatial resolution, readily differentiating viable from necrotic tissue in
      comparison to conventional ultrasound without the risk of iodine contrast agents
      and ionizing radiation of repeated CECT examinations.

PMID- 29204239
TI  - Wilkie's syndrome.
AB  - Superior mesenteric artery syndrome, also known as Wilkie's syndrome, is a rare
      vascular disease caused by the anomalous course of the superior mesenteric artery
      arising from the abdominal aorta with a smaller angle than the norm (<22 degrees
      ). The reduced angle compresses the structures situated between the aorta and the
      superior mesenteric artery, such as the duodenum and left renal vein; this can
      determine painful crises, intestinal subocclusions, and left varicocele. This
      syndrome can be congenital or acquired. The acquired type is more common and is
      generally caused by reduced perivascular fat surrounding the abdominal aorta and
      the superior mesenteric artery; this form is common among anorexic patients that
      have had a rapid weight loss. We present the case of a female patient who
      suffered from repeated postprandial vomiting and who lost 12 kg in 4 months. B
      mode ultrasound imaging revealed evidence of a reduced angle between the aorta
      and the superior mesenteric artery, as found in Wilkie's syndrome. After
      diagnosis, the patient followed a high-calorie diet, and 2 months later an
      ultrasound scan proved the restoration of the aorto-mesenteric angle as a
      consequence of increased perivascular fat with regression of symptoms.

PMID- 29204240
TI  - A rare case of diffuse neurofibroma masquerading as a hemangioma: a radiological
      perspective.
AB  - Diffuse neurofibroma is a rarely encountered subtype of neurofibroma but the most
      common to be misdiagnosed. Its imaging appearance is very similar to that of a
      vascular malformation, and it is often labelled one until a biopsy proves it to
      be otherwise. The infrequency of its association with neurofibromatosis makes it
      a rare and difficult diagnosis. Here, we report the case of a 16-year-old girl
      who presented with the complaint of a gradually progressive swelling around the
      right ankle and heel, which was initially diagnosed as a case of a vascular
      malformation. However, it subsequently turned out to be a diffuse neurofibroma.

PMID- 29204241
TI  - Image-guided thermal ablation of benign thyroid nodules.
AB  - Purpose: To clarify some relevant and significant inconsistencies and
      inaccuracies in review by Mainini et al. entitled "Image-guided thermal ablation
      of benign thyroid nodules" published in Journal of Ultrasound to avoid giving
      incorrect information to the reader and prevent that operators make wrong choices
      in the use of various devices and technologies available. Results: Total cases
      treated with radiofrequency would be 2388 and not 2435 as reported in Table 1 of
      this review. The major, minor complications, and side effects in the partial
      group treated with laser technique and reported in this review are actually 1.2,
      3.8, and 35.4%, respectively. In series of patients treated with laser ablation,
      including a total of 2345 patients, major and minor complications are 0.7 and
      1.4%, respectively. The major complications of laser technology are less severe
      than RFA. Conclusions: Several points regarding the paper by Mainini et al. need
      to be discussed, and I advocate authors for replying to my considerations to
      clarify the issues raised.

PMID- 29204242
TI  - Color-Doppler ultrasound in the evaluation of oral lesions.

PMID- 29204243
TI  - Erratum to: Inter-device reproducibility of retrobulbar blood flow velocity
      measurements in healthy subjects using color Doppler imaging.
AB  - [This corrects the article DOI: 10.1007/s40477-016-0194-5.].

PMID- 29204244
TI  - Microfluidic platform for characterizing TCR-pMHC interactions.
AB  - The physical characteristics of the T cell receptor (TCR)-peptide-major
      histocompatibility complex (pMHC) interaction are known to play a central role in
      determining T cell function in the initial stages of the adaptive immune
      response. State-of-the-art assays can probe the kinetics of this interaction with
      single-molecular-bond resolution, but this precision typically comes at the cost
      of low throughput, since the complexity of these measurements largely precludes
      "scaling up." Here, we explore the feasibility of detecting specific TCR-pMHC
      interactions by flowing T cells past immobilized pMHC and measuring the reduction
      in cell speed due to the mechanical force of the receptor-ligand interaction. To
      test this new fluidic measurement modality, we fabricated a microfluidic device
      in which pMHC-coated beads are immobilized in hydrodynamic traps along the length
      of a serpentine channel. As T cells flow past the immobilized beads, their change
      in speed is tracked via microscopy. We validated this approach using two model
      systems: primary CD8+ T cells from an OT-1 TCR transgenic mouse with beads
      conjugated with H-2Kb:SIINFEKL, and Jurkat T cells with beads conjugated with
      anti-CD3 and anti-CD28 antibodies.

PMID- 29204245
TI  - Microfluidic chip for automated screening of carbon dioxide conditions for
      microalgal cell growth.
AB  - This paper reports on a microfluidic device capable of screening carbon dioxide
      (CO2) conditions for microalgal cell growth. The device mainly consists of a
      microfluidic cell culture (MCC) unit, a gas concentration gradient generator
      (CGG), and an in-line cell growth optical measurement unit. The MCC unit is
      structured with multiple aqueous-filled cell culture channels at the top layer,
      multiple CO2 flow channels at the bottom layer, and a commercial hydrophobic gas
      semipermeable membrane sandwiched between the two channel layers. The CGG unit
      provides different CO2 concentrations to support photosynthesis of microalgae in
      the culture channels. The integration of the commercial gas semipermeable
      membrane into the cell culture device allows rapid mass transport and uniform
      distribution of CO2 inside the culture medium without using conventional
      agitation-assisted convection methods, because the diffusion of CO2 from the gas
      flow channels to the culture channels is fast over a small length scale. In
      addition, automated in-line monitoring of microalgal cell growth is realized via
      the optical measurement unit that is able to detect changes in the light
      intensity transmitted through the cell culture in the culture channels. The
      microfluidic device also allows a simple grayscale analysis method to quantify
      the cell growth. The utility of the system is validated by growing Chlamydomonas
      reinhardtii cells under different low or very-low CO2 levels below the nominal
      ambient CO2 concentration.

PMID- 29204246
TI  - Constricted microfluidic devices to study the effects of transient high shear
      exposure on platelets.
AB  - Due to the critical roles that platelets play in thrombosis during many
      biological and pathological events, altered platelet function may be a key
      contributor to altered hemostasis, leading to both thrombotic and hemorrhagic
      complications. Platelet adhesion at arterial shear rates occurs through binding
      to von Willebrand Factor via the glycoprotein (GP) GPIb receptor. GPIb binding
      can induce platelet activation distinguishable by P-selectin (CD62P) surface
      expression and alphaIIbbeta3 activation, resulting in platelet aggregation and
      formation of the primary hemostatic plug to stop bleeding. Previous studies have
      used cone and plate viscometers to examine pathologic blood flow conditions,
      applied shear rates that are relatively low, and examined exposure times that are
      orders of magnitude longer compared to conditions present in ventricular assist
      devices, mechanical heart valves, or pathologic states such as stenotic arteries.
      Here, we evaluate the effect of short exposure to high shear on granule release
      and receptor shedding utilizing a constricted microfluidic device in conjunction
      with flow cytometry and enzyme-linked immunosorbent assay. In this study,
      platelets were first perfused through microfluidic channels capable of producing
      shear rates of 80 000-100 000 s-1 for exposure times of 0-73 ms. We investigated
      platelet activation by measuring the expression level of CD62P (soluble and
      surface expressed), platelet factor 4 (PF4), and beta-thromboglobulin (betaTG).
      In addition, we measured potential platelet receptor shedding of GPVI and GPIb
      using flow cytometry. The results showed that a single pass to high shear with
      short exposure times (milliseconds) had no effect on the levels of CD62P, GPVI
      and GPIb, or on the release of alpha granule content (PF4, betaTG, and sP
      selectin).

PMID- 29204247
TI  - Oxidative Stress Modulation and ROS-Mediated Toxicity in Cancer: A Review on In
      Vitro Models for Plant-Derived Compounds.
AB  - Medicinal and aromatic plants (MAPs) are known and have been long in use for a
      variety of health and cosmetics applications. Potential pharmacological usages
      that take advantage of bioactive plant-derived compounds' antimicrobial,
      antifungal, anti-inflammatory, and antioxidant properties are being developed and
      many new ones explored. Some phytochemicals could trigger ROS-mediated
      cytotoxicity and apoptosis in cancer cells. A lot of effort has been put into
      investigating novel active constituents for cancer therapeutics. While other
      plant-derived compounds might enhance antioxidant defenses by either radical
      scavenging or stimulation of intracellular antioxidant enzymes, the generation of
      reactive oxygen species (ROS) leading to oxidative stress is one of the
      strategies that may show effective in damaging cancer cells. The biochemical
      pathways involved in plant-derived bioactive compounds' properties are complex,
      and in vitro platforms have been useful for a comprehensive understanding of the
      mechanism of action of these potential anticancer drugs. The present review aims
      at compiling the findings of particularly interesting studies that use cancer
      cell line models for assessment of antioxidant and oxidative stress modulation
      properties of plant-derived bioactive compounds.

PMID- 29204248
TI  - Ginsenoside Rg1 Ameliorates Behavioral Abnormalities and Modulates the
      Hippocampal Proteomic Change in Triple Transgenic Mice of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, so
      far, there are no effective measures to prevent and cure this deadly condition.
      Ginsenoside Rg1 (Rg1) was shown to improve behavioral abnormalities in AD;
      however, the potential mechanisms remain unclear. In this study, we pretreated 7
      month-old 3xTg-AD mice for 6 weeks with Rg1 and evaluated the effects of Rg1 on
      the behaviors and the protein expression of hippocampal tissues. The behavioral
      tests showed that Rg1 could improve the memory impairment and ameliorate the
      depression-like behaviors of 3xTg-AD mice. Proteomic results revealed a total of
      28 differentially expressed hippocampal proteins between Rg1-treated and
      nontreated 3xTg-AD mice. Among these proteins, complexin-2 (CPLX2), synapsin-2
      (SYN2), and synaptosomal-associated protein 25 (SNP25) were significantly
      downregulated in the hippocampus of 3xTg-AD mice compared with the WT mice, and
      the treatment of Rg1 modulated the expression of CPLX2 and SNP25 in the
      hippocampus of 3xTg-AD mice. The expression of CPLX2, SYN2, and SNP25 was further
      validated by Western blot analysis. Taken together, we concluded that Rg1 could
      be a potential candidate drug to improve the behavioral deficits in AD via
      modulating the expression of the proteins (i.e., CPLX2, SYN2, and SNP25).

PMID- 29204249
TI  - Dietary Polyphenols in the Prevention of Stroke.
AB  - Polyphenols have an important protective role against a number of diseases, such
      as atherosclerosis, brain dysfunction, stroke, cardiovascular diseases, and
      cancer. Cardiovascular diseases are the number one cause of death worldwide: more
      people die annually from cardiovascular diseases than from any other cause. The
      most important behavioural risk factors of heart disease and stroke are unhealthy
      diet, physical inactivity, tobacco use, and excess alcohol intake. The dietary
      consumption of polyphenols has shown to be inversely associated with morbidity
      and mortality by cardio- and cerebrovascular diseases. It is well-known that the
      protective effects of polyphenols in vivo depend on the grade how they are
      extracted from food and on their intestinal absorption, metabolism, and
      biological action with target tissues. The aim of this review was to summarise
      the relation between polyphenols of different plant sources and stroke in human
      intervention studies, animal models, and in vitro studies.

PMID- 29204250
TI  - Generation and Role of Reactive Oxygen and Nitrogen Species Induced by Plasma,
      Lasers, Chemical Agents, and Other Systems in Dentistry.
AB  - The generation of reactive oxygen and nitrogen species (RONS) has been found to
      occur during inflammatory procedures, during cell ischemia, and in various
      crucial developmental processes such as cell differentiation and along cell
      signaling pathways. The most common sources of intracellular RONS are the
      mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In
      this review, we analyzed the extracellular and intracellular sources of reactive
      species, their cell signaling pathways, the mechanisms of action, and their
      positive and negative effects in the dental field. In dentistry, ROS can be found
      in lasers, photosensitizers, bleaching agents, cold plasma, and even resin
      cements, all of which contribute to the generation and prevalence of ROS.
      Nonthermal plasma has been used as a source of ROS for biomedical applications
      and has the potential for use with dental stem cells as well. There are different
      types of dental stem cells, but their therapeutic use remains largely untapped,
      with the focus currently on only periodontal ligament stem cells. More research
      is necessary in this area, including studies about ROS mechanisms with dental
      cells, along with the utilization of reactive species in redox medicine. Such
      studies will help to provide successful treatment modalities for various
      diseases.

PMID- 29204252
TI  - Paradoxical expression pattern of the epithelial mesenchymal transition-related
      biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal
      stromal tumors.
AB  - AIM: To evaluate the immunohistochemical (IHC) expression of five biomarkers,
      commonly involved in epithelial mesenchymal/mesenchymal epithelial transition
      (EMT/MET), in gastrointestinal stromal tumors (GISTs). METHODS: In 80 consecutive
      GISTs the IHC examinations were performed using the EMT-related antibodies E
      cadherin, N-cadherin, SLUG, V-set and immunoglobulin domain containing 1 (VSIG1)
      and CD44. RESULTS: The positivity rate was 88.75% for SLUG, 83.75% for VSIG1,
      36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the
      examined markers and clinicopathological parameters. Nuclear positivity for SLUG
      and VSIG1 was observed in all cases with distant metastasis. The extra
      gastrointestinal stromal tumors (e-GISTs) expressed nuclear positivity for VSIG1
      and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall
      survival was mainly dependent on VSIG1 negativity (P = 0.01) and nuclear
      positivity for SLUG and/or CD44. CONCLUSION: GIST aggressivity may be induced by
      nuclear up-regulation of SLUG and loss or cytoplasm-to-nuclear translocation of
      VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The
      CD44, but not N-cadherin, might also have an independent prognostic value in
      these tumors. The role of the EMT/MET-related transcription factors in the
      evolution of GISTs, should be revisited with a larger dataset. This is the first
      study exploring the IHC pattern of VSIG1 in GISTs.

PMID- 29204251
TI  - Roles and Mechanisms of Herbal Medicine for Diabetic Cardiomyopathy: Current
      Status and Perspective.
AB  - Diabetic cardiomyopathy is one of the major complications among patients with
      diabetes mellitus. Diabetic cardiomyopathy (DCM) is featured by left ventricular
      hypertrophy, myocardial fibrosis, and damaged left ventricular systolic and
      diastolic functions. The pathophysiological mechanisms include metabolic-altered
      substrate metabolism, dysfunction of microvascular, renin-angiotensin-aldosterone
      system (RAAS) activation, oxidative stress, cardiomyocyte apoptosis,
      mitochondrial dysfunction, and impaired Ca2+ handling. An array of molecules and
      signaling pathways such as p38 mitogen-activated protein kinase (p38 MAPK), c-Jun
      N-terminal kinase (JNK), and extracellular-regulated protein kinases (ERK) take
      roles in the pathogenesis of DCM. Currently, there was no remarkable effect in
      the treatment of DCM with application of single Western medicine. The myocardial
      protection actions of herbs have been gearing much attention. We present a review
      of the progress research of herbal medicine as a potential therapy for diabetic
      cardiomyopathy and the underlying mechanisms.

PMID- 29204253
TI  - Value of histomorphometric tumour thickness and smoothelin for conventional m
      classification in early oesophageal adenocarcinoma.
AB  - AIM: To test the validity of tumour thickness measurement in distinguishing
      between the different infiltration depths, especially when the duplication of
      muscularis mucosae cannot be demarcated clearly. METHODS: We re-evaluated 100
      completely embedded Barrett's adenocarcinomas regarding m-classification, maximum
      tumour thickness, and muscularis mucosae duplication. For validation, smoothelin
      staining was performed on a subset of cases. RESULTS: The m1-, m2- and m3
      classified adenocarcinomas showed a significant lower tumour thickness compared
      to the m4- and sm1-classified lesions (P < 0.001). Smoothelin staining determined
      a clear muscularis mucosae duplication in 64% of the tested samples and enabled
      the differentiation of the two layers in diffuse and merged splits. CONCLUSION:
      Tumour thickness in early oesophageal adenocarcinoma significantly correlates
      with the depth of infiltration and demonstrates its worth as an accurate pT
      classification in non-polypoid lesions. We created a new algorithm, which
      combines histomorphology with morphometric analyses. It is noteworthy that it
      facilitates the assessment of mucosal vs submucosal infiltration depth. The
      smoothelin staining strengthened our results of the tumour thickness evaluation
      and can be used in cases of doubt.

PMID- 29204254
TI  - Gastric metastasis from ovarian adenocarcinoma presenting as a subepithelial
      tumor and diagnosed by endoscopic ultrasound-guided tissue acquisition.
AB  - We describe an uncommon case of a patient with a metastatic adenocarcinoma of
      ovarian origin presented as a gastric subepithelial tumor (SET) and that was
      diagnosed by endoscopic ultrasound fine-needle biopsy (EUS-FNB). Malignant
      gastric lesions are rarely metastatic and the primary tumor is mainly breast,
      lung, esophageal cancer or cutaneous melanoma. Gastric metastasis from ovarian
      cancer is unusual, presenting synchronously with the primary tumor but also
      several years later than the initial diagnosis. From an endoscopic point of view,
      gastric metastasis does not present specific features. They may mimic both a
      primary gastric tumor or, less frequently, an SET. This case demonstrates the
      importance of EUS-FNB in distinguishing SETs and how this may alter treatment and
      prognosis.

PMID- 29204256
TI  - Reproductive disturbances among Saudi adolescent girls and young women with type
      1 diabetes mellitus.
AB  - AIM: To identify reproductive disturbances among adolescent girls and young women
      with type 1 diabetes mellitus (T1DM) in Saudi Arabia. METHODS: This cross
      sectional study was conducted among 102 female with T1DM, (aged 13-29 years) who
      attended the Diabetes Clinic at Diabetes Treatment Center, Prince Sultan Military
      Medical City, Saudi Arabia between April 2015 to March 2016. Clinical history,
      anthropometric characteristics and reproductive disturbance were collected
      through a questionnaire. RESULTS: Of 102 patients included in this analysis,
      26.5% (27/102) were reported that they experienced an irregular menses. Of these
      patients, when compared to whose diabetes was diagnosed before menarche (35.4%,
      17/48), patients diagnosed with diabetes after menarche (18.5%, 10/54) showed
      significantly less irregular menses (difference 16.9%, P = 0.04). Similarly,
      compared to patients diagnosed with diabetes prior to menarche (mean age 12.9
      years; n = 48), patients diagnosed with diabetes after menarche (mean age 12.26
      years; n = 54) were found to have 0.64 years delay in the age of menarche (P =
      0.04). Among the studied patients, 15.7% (16/102) had polycystic ovary syndrome
      (PCOS). Of these PCOS patients, 37.5% (6/16) had irregular menses, 6.3% (1/16)
      had Celiac disease, 37.5% (6/16) had Hashimoto thyroiditis and 18.7% (3/16) had
      acne. CONCLUSION: More than one fourth of the study population with T1DM
      experiencing an irregular menses. Adolescent girls and young women diagnosed with
      diabetes prior to menarche showed higher menstrual irregularity and a delay in
      the age of menarche.

PMID- 29204257
TI  - Feature-Based Retinal Image Registration Using D-Saddle Feature.
AB  - Retinal image registration is important to assist diagnosis and monitor retinal
      diseases, such as diabetic retinopathy and glaucoma. However, registering retinal
      images for various registration applications requires the detection and
      distribution of feature points on the low-quality region that consists of vessels
      of varying contrast and sizes. A recent feature detector known as Saddle detects
      feature points on vessels that are poorly distributed and densely positioned on
      strong contrast vessels. Therefore, we propose a multiresolution difference of
      Gaussian pyramid with Saddle detector (D-Saddle) to detect feature points on the
      low-quality region that consists of vessels with varying contrast and sizes. D
      Saddle is tested on Fundus Image Registration (FIRE) Dataset that consists of 134
      retinal image pairs. Experimental results show that D-Saddle successfully
      registered 43% of retinal image pairs with average registration accuracy of 2.329
      pixels while a lower success rate is observed in other four state-of-the-art
      retinal image registration methods GDB-ICP (28%), Harris-PIIFD (4%), H-M (16%),
      and Saddle (16%). Furthermore, the registration accuracy of D-Saddle has the
      weakest correlation (Spearman) with the intensity uniformity metric among all
      methods. Finally, the paired t-test shows that D-Saddle significantly improved
      the overall registration accuracy of the original Saddle.

PMID- 29204255
TI  - Bariatric surgery and long-term nutritional issues.
AB  - Bariatric surgery is recognized as a highly effective therapy for obesity since
      it accomplishes sustained weight loss, reduction of obesity-related comorbidities
      and mortality, and improvement of quality of life. Overall, bariatric surgery is
      associated with a 42% reduction of the cardiovascular risk and 30% reduction of
      all-cause mortality. This review focuses on some nutritional consequences that
      can occur in bariatric patients that could potentially hinder the clinical
      benefits of this therapeutic option. All bariatric procedures, to variable
      degrees, alter the anatomy and physiology of the gastrointestinal tract; this
      alteration makes these patients more susceptible to developing nutritional
      complications, namely, deficiencies of macro- and micro-nutrients, which could
      lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of
      note is the evidence that most obese patients present a number of nutritional
      deficits already prior to surgery, the most important being vitamin D and iron
      deficiencies. This finding prompts the need for a complete nutritional assessment
      and, eventually, an adequate correction of pre-existing deficits before surgery.
      Another critical issue that follows bariatric surgery is post-operative weight
      regain, which is commonly associated with the relapse of obesity-related co
      morbidities. Nu-tritional complications associated with bariatric surgery can be
      prevented by life-long nutritional monitoring with the administration of multi
      vitamins and mineral supplements according to the patient's needs.

PMID- 29204258
TI  - A Remote Health Monitoring System for the Elderly Based on Smart Home Gateway.
AB  - This paper proposed a remote health monitoring system for the elderly based on
      smart home gateway. The proposed system consists of three parts: the smart
      clothing, the smart home gateway, and the health care server. The smart clothing
      collects the elderly's electrocardiogram (ECG) and motion signals. The home
      gateway is used for data transmission. The health care server provides services
      of data storage and user information management; it is constructed on the Windows
      Apache-MySQL-PHP (WAMP) platform and is tested on the Ali Cloud platform. To
      resolve the issues of data overload and network congestion of the home gateway,
      an ECG compression algorithm is applied. System demonstration shows that the ECG
      signals and motion signals of the elderly can be monitored. Evaluation of the
      compression algorithm shows that it has a high compression ratio and low
      distortion and consumes little time, which is suitable for home gateways. The
      proposed system has good scalability, and it is simple to operate. It has the
      potential to provide long-term and continuous home health monitoring services for
      the elderly.

PMID- 29204260
TI  - The evolving role of targeted biological agents in the management of indolent B
      cell lymphomas.
AB  - Improved understanding of the mechanisms of lymphomagenesis has resulted in a
      surge of development for new targeted agents. An impressive number of biological
      agents targeting different steps in the pathways of tumor proliferation, survival
      and apoptosis have become available. The management of patients with indolent non
      Hodgkin lymphomas (iNHLs) is rapidly transforming with incorporation of those
      targeted biological agents into the front-line and relapsed/refractory setting.
      This review highlights several categories of novel biological agents and will
      discuss their potential role in the contemporary management of patients with
      iNHLs.

PMID- 29204259
TI  - Early development of infants with neurofibromatosis type 1: a case series.
AB  - Background: Prospective studies of infants at familial risk for autism spectrum
      disorder (ASD) have yielded insights into the earliest signs of the disorder but
      represent heterogeneous samples of unclear aetiology. Complementing this approach
      by studying cohorts of infants with monogenic syndromes associated with high
      rates of ASD offers the opportunity to elucidate the factors that lead to ASD.
      Methods: We present the first report from a prospective study of ten 10-month-old
      infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high
      prevalence of ASD or ASD symptomatology. We compared data from infants with NF1
      to a large cohort of infants at familial risk for ASD, separated by outcome at
      age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n =
      89), and low-risk controls (n = 75). Domains assessed at 10 months by parent
      report and examiner observation include cognitive and adaptive function, sensory
      processing, social engagement, and temperament. Results: Infants with NF1 showed
      striking impairments in motor functioning relative to low-risk infants; this
      pattern was seen in infants with later ASD from the familial cohort (HR-ASD).
      Both infants with NF1 and the HR-ASD group showed communication delays relative
      to low-risk infants. Conclusions: Ten-month-old infants with NF1 show a range of
      developmental difficulties that were particularly striking in motor and
      communication domains. As with HR-ASD infants, social skills at this age were not
      notably impaired. This is some of the first information on early neurodevelopment
      in NF1. Strong inferences are limited by the sample size, but the findings
      suggest implications for early comparative developmental science and highlight
      motor functioning as an important domain to inform the development of relevant
      animal models. The findings have clinical implications in indicating an important
      focus for early surveillance and remediation in this early diagnosed genetic
      disorder.

PMID- 29204261
TI  - Recombinant human factor VIIa (rFVIIa) in hemophilia: mode of action and evidence
      to date.
AB  - Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both
      in the treatment and prevention of hemorrhagic complications due to hemophilia
      with inhibitor. In such cases, antihemophilic factors cannot be used. The normal
      physiology of factor VII/ factor VIIa (FVII/FVIIa) in the hemostatic process
      requires the presence of tissue factor (TF) that links to FVII leading to a FVIIa
      TF complex which activates both factor X and factor IX. The therapeutic use of
      rFVIIa requires high amount of FVIIa. Some studies demonstrate that FVIIa at high
      doses still requires tissue factor for function, whereas others suggest that
      FVIIa activates FX directly on the platelet surface, in a TF-independent manner.
      In the present article, we discuss the arguments supporting both TF-dependent and
      TF-independent modes of action. Finally, the coexistence of both TF-dependent and
      TF-independent mechanisms cannot be excluded.

PMID- 29204262
TI  - The role of oral anticoagulant therapy in patients with acute coronary syndrome.
AB  - Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist
      represents the current standard of care to prevent atherothrombotic recurrences
      in patients with acute coronary syndrome (ACS). However, despite the use of DAPT,
      the recurrence rate of cardiovascular ischemic events still remains high. This
      persistent risk may be in part attributed to the sustained activation of the
      coagulation cascade leading to generation of thrombin, which may continue to play
      a key role in thrombus formation. The use of vitamin K antagonists (VKAs) as a
      strategy to reduce atherothrombotic recurrences after an ACS has been previously
      tested, leading to overall unfavorable outcomes due to the high risk of bleeding
      complications. The recent introduction of non-VKA oral anticoagulants (NOACs),
      characterized by a better safety profile and ease of use compared with VKA, has
      led to a reappraisal of the use of oral anticoagulant therapy for secondary
      prevention in ACS patients. The present article provides an overview of the
      rationale and prognostic role of oral anticoagulant therapy in ACS patients as
      well as recent updated clinical data, in particular with NOACs, in the field and
      future perspectives on this topic.

PMID- 29204264
TI  - Curvature Blindness Illusion.
AB  - We report a novel illusion--curvature blindness illusion: a wavy line is
      perceived as a zigzag line. The following are required for this illusion to
      occur. First, the luminance contrast polarity of the wavy line against the
      background is reversed at the turning points. Second, the curvature of the wavy
      line is somewhat low; the right angle is too steep to be perceived as an
      illusion. This illusion implies that, in order to perceive a gentle curve, it is
      necessary to satisfy more conditions--constant contrast polarity--than perceiving
      an obtuse corner. It is notable that observers exactly "see" an illusory zigzag
      line against a physically wavy line, rather than have an impaired perception. We
      propose that the underlying mechanisms for the gentle curve perception and those
      of obtuse corner perception are competing with each other in an imbalanced way
      and the percepts of corner might be dominant in the visual system.

PMID- 29204265
TI  - Using deep learning to improve medication safety: the untapped potential of
      social media.

PMID- 29204263
TI  - The Oscillating Potential Model of Visually Induced Vection.
AB  - Visually induced illusions of self-motion are often referred to as vection. This
      article developed and tested a model of responding to visually induced vection.
      We first constructed a mathematical model based on well-documented
      characteristics of vection and human behavioral responses to this illusion. We
      then conducted 10,000 virtual trial simulations using this Oscillating Potential
      Vection Model (OPVM). OPVM was used to generate simulated vection onset,
      duration, and magnitude responses for each of these trials. Finally, we compared
      the properties of OPVM's simulated vection responses with real responses obtained
      in seven different laboratory-based vection experiments. The OPVM output was
      found to compare favorably with the empirically obtained vection data.

PMID- 29204266
TI  - Pegloticase in gout treatment - safety issues, latest evidence and clinical
      considerations.
AB  - Gout is a common rheumatic condition, with increasing prevalence in recent
      decades. The mainstay of treatment for gout is oral urate-lowering therapy (ULT),
      typically with xanthine oxidase inhibitors (XOIs). Unfortunately, a proportion of
      patients have persistent gout that is refractory to ULT. Pegloticase, a
      recombinant pegylated uricase, has been approved by the US Food and Drug
      Administration for the treatment of refractory gout. However, concern has been
      raised regarding the risk of infusion reactions, which are now understood to be
      largely due to the development of antipegloticase antibodies. Discontinuation of
      pegloticase upon failure to lower serum urate has been shown to markedly reduce
      infusion reaction risk, but deprives patients of what, in many cases, is a last
      resort treatment. In this manuscript, we review the rationale, mechanism of
      action, efficacy and safety of pegloticase. Additionally, we focus on potential
      strategies to reduce pegloticase immunogenicity and potentially make this
      important agent available to a wider group of patients requiring treatment.

PMID- 29204267
TI  - Tamsulosin induced diarrhea: a case report.

PMID- 29204269
TI  - A systematic review and overview of health economic evaluations of emergency
      laparotomy.
AB  - Background: Little is known about the economic impact of emergency laparotomy
      (EL) surgery in healthcare systems around the world. The aim of this systematic
      review is to describe the primary resource utilisation, healthcare economic and
      societal costs of EL in adults in different countries. Methods: MEDLINE, EMBASE,
      ISI Web of Knowledge, Cochrane Central Register Controlled Trials, Cochrane
      Database of Systematic Reviews and CINAHL were searched for full and partial
      economic analyses of EL published between 1 January 1991 and 31 December 2015.
      Quality of studies was assessed using the Consensus on Health Economic Criteria
      (CHEC) checklist. Results: Sixteen studies were included from a range of
      countries. One study was a full economic analysis. Fifteen studies were partial
      economic evaluations. These studies revealed that emergency abdominal surgery is
      expensive compared to similar elective surgery when comparing primary resource
      utilisation costs, with an important societal impact. Most contemporaneous
      studies indicate that in-hospital costs for EL are in excess of US$10,000 per
      patient episode, rising substantially when societal costs are considered.
      Discussion: EL is a high-risk and costly procedure with a disproportionate
      financial burden for healthcare providers, relative to national funding
      provisions and wider societal cost impact. There is substantial heterogeneity in
      the methodologies and quality of published economic evaluations of EL; therefore,
      the true economic costs of EL are yet to be fully defined. Future research should
      focus on developing strategies to embed health economic evaluations within
      national programmes aiming to improve EL care, including developing the required
      measures and infrastructure. Conclusions: Emergency laparotomy is expensive, with
      a significant cost burden to healthcare and systems and society worldwide. Novel
      strategies for reducing this econmic burden should urgently be explored if
      greater access to this type of surgery is to be pursued as a global health
      target. Trial registration: PROSPERO registration no. 42015027210.

PMID- 29204268
TI  - Role of metastasis-induced protein S100A4 in human non-tumor pathophysiologies.
AB  - S100A4, an important member of the S100 family of proteins, is best known for its
      significant role in promoting cancer progression and metastasis. In addition to
      its expression in tumors, upregulation of S100A4 expression has been associated
      with various non-tumor pathophysiology processes. However, the mechanisms
      underlying the role of S100A4 remain unclear. Activated "host" cells
      (fibroblasts, immunocytes, vascular cells, among others) secrete S100A4 into the
      extracellular space in various non-tumor human disorders, where it executes its
      biological functions by interacting with intracellular target proteins. However,
      the exact molecular mechanisms underlying these interactions in different non
      tumor pathophysiologies vary, and S100A4 is likely one of the cross-linking
      factors that acts as common intrinsic constituents of biological mechanisms.
      Numerous studies have indicated that the S100A4-mediated epithelial-mesenchymal
      transition plays a vital role in the occurrence and development of various non
      tumor pathophysiologies. Epithelial-mesenchymal transition can be categorized
      into three general subtypes based on the phenotype and function of the output
      cells. S100A4 regulates tissue fibrosis associated with the type II epithelial
      mesenchymal transition via various signaling pathways. Additionally, S100A4
      stimulates fibroblasts to secrete fibronectin and collagen, thus forming the
      structural components of the extracellular matrix (ECM) and stimulating their
      deposition in tissues, contributing to the formation of a pro-inflammatory niche.
      Simultaneously, S100A4 enhances the motility of macrophages, neutrophils, and
      leukocytes and promotes the recruitment and chemotaxis of these inflammatory
      cells to regulate inflammation and immune functions. S100A4 also exerts a
      neuroprotective pro-survival effect on neurons by rescuing them from brain injury
      and participates in angiogenesis by interacting with other target molecules. In
      this review, we summarize the role of S100A4 in fibrosis, inflammation, immune
      response, neuroprotection, angiogenesis, and some common non-tumor diseases as
      well as its possible involvement in molecular pathways and potential clinical
      value.

PMID- 29204270
TI  - Comparison of risk-scoring systems in the prediction of outcome after liver
      resection.
AB  - Background: Risk prediction techniques commonly used in liver surgery include the
      American Society of Anesthesiologists (ASA) grading, Charlson Comorbidity Index
      (CCI) and cardiopulmonary exercise tests (CPET). This study compares the utility
      of these techniques along with the number of segments resected as predictive
      tools in liver surgery. Methods: A review of a unit database of patients
      undergoing liver resection between February 2008 and January 2015 was undertaken.
      Patient demographics, ASA, CCI and CPET variables were recorded along with
      resection size. Clavien-Dindo grade III-V complications were used as a composite
      outcome in analyses. Association between predictive variables and outcome was
      assessed by univariate and multivariate techniques. Results: One hundred and
      seventy-two resections in 168 patients were identified. Grade III-V complications
      occurred after 42 (24.4%) liver resections. In univariate analysis of CPET
      variables, ventilatory equivalents for CO2 (VEqCO2) was associated with outcome.
      CCI score, but not ASA grade, was also associated with outcome. In multivariate
      analysis, the odds ratio of developing grade III-V complications for incremental
      increases in VEqCO2, CCI and number of liver segments resected were 1.09, 1.49
      and 2.94, respectively. Conclusions: Of the techniques evaluated, resection size
      provides the simplest and most discriminating predictor of significant
      complications following liver surgery.

PMID- 29204272
TI  - Novel antibiotic combinations proposed for treatment of Burkholderia cepacia
      complex infections.
AB  - Effective strategies to manage Burkholderia cepacia complex (Bcc) infections in
      cystic fibrosis (CF) patients are lacking. We tested combinations of clinically
      available antibiotics and show that moxifloxacin-ceftazidime could inhibit 16 Bcc
      clinical isolates at physiologically achievable concentrations. Adding low dose
      of colistin improved the efficacy of the combo, especially at conditions
      mimicking CF respiratory secretions.

PMID- 29204273
TI  - Specific serum antibody binding to phosphorylated and non-phosphorylated tau in
      non-cognitively impaired, mildly cognitively impaired, and Alzheimer's disease
      subjects: an exploratory study.
AB  - Background: Tau vaccination and administration of anti-tau antibodies can prevent
      pathology and cognitive impairment in transgenic mouse models of tauopathy,
      suggesting that therapies which increase anti-tau antibodies might slow the
      development and/or progression of Alzheimer's disease (AD). The extent to which
      individuals with no cognitive impairment (NCI) possess serum anti-tau antibodies,
      and whether their concentrations of these antibodies differ from anti-tau
      antibody levels in persons with mild cognitive impairment (MCI) or AD, are
      unclear. Previous studies measuring these antibodies did not account for antibody
      polyvalent binding, which can be extensive, nor that antibody binding to
      phosphorylated tau peptides could be due to binding to non-phosphorylated
      epitopes on those peptides. Methods: An ELISA controlling for these factors was
      used to measure the specific binding of serum IgG and IgM to phosphorylated
      ("pTau;" phosphorylated at Serine-199 and Serine-202) and non-phosphorylated
      ("non-pTau") tau 196-207 in subjects with NCI, MCI, or AD (n = 10/group). Between
      group differences in these antibody levels were evaluated for statistical
      significance, and correlations were examined in pooled data from all subjects
      between these antibody levels and subject age, global cognitive functioning, and
      NFT counts. Results: Specific IgG binding to pTau and non-pTau was detected in
      all subjects except for one NCI control. Specific IgM binding was detected to
      pTau in all subjects except for two AD patients, and to non-pTau in all subjects.
      Mean pTau IgG was increased in MCI subjects by 53% and 70% vs. AD and NCI
      subjects respectively (both p < 0.05), while no significant differences were
      found between groups for non-pTau IgG (p = 0.052), pTau IgM, or non-pTau IgM. Non
      pTau IgG was negatively associated with global cognition (Spearman rho = -0.50).
      Conclusions: Specific binding of serum IgG and IgM to phosphorylated and non
      phosphorylated tau may be present in older persons regardless of their cognitive
      status. Serum IgG to phosphorylated tau may be increased in individuals with MCI,
      but this unexpected finding requires confirmation. The approach used in this
      study to measure specific serum antibodies to phosphorylated tau should be useful
      for measuring antibodies to other post-translationally-modified proteins that are
      of relevance to neurodegenerative disorders.

PMID- 29204274
TI  - Clinical use of adipose-derived stem cells: European legislative issues.
AB  - Objective: With this study we analyse the current European legislation in order
      to provide guidance for regenerative medicine professionals on correct Adipose
      derived Stem Cells (ASCs) isolation and use protocols for clinical applications.
      Materials and Methods: The European Medicines Agency (EMA) considers that ASCs
      does not fall within the definition of an advanced therapy medicinal product if
      the cells have not been subjected to a substantial manipulation, and the mode of
      action of the cells (contribute to and enhance tissue renewal and turnover of the
      subcutaneous tissue) is considered to be homologous to the donor fat tissue.
      Results: Collagenase digestion, as well as cell culturing, is considered to be a
      substantial manipulation. Only transplantation of a non-manipulated tissue to
      another location in the same anatomical or histological environment is considered
      to be homologous. Conclusions: According to these considerations, ASCs should be
      not-cultured, isolated mechanically and used only in the subcutaneous tissue.

PMID- 29204271
TI  - Genome sequencing and analysis of the first spontaneous Nanosilver resistant
      bacterium Proteus mirabilis strain SCDR1.
AB  - Background: P. mirabilis is a common uropathogenic bacterium that can cause major
      complications in patients with long-standing indwelling catheters or patients
      with urinary tract anomalies. In addition, P. mirabilis is a common cause of
      chronic osteomyelitis in Diabetic foot ulcer (DFU) patients. We isolated P.
      mirabilis SCDR1 from a Diabetic ulcer patient. We examined P. mirabilis SCDR1
      levels of resistance against Nanosilver colloids, the commercial Nanosilver and
      silver containing bandages and commonly used antibiotics. We utilized next
      generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and
      pathogenomics in the characterization of the infectious pathogen. Results: P.
      mirabilis SCDR1 was the first Nanosilver resistant isolate collected from a
      diabetic patient polyclonal infection. P. mirabilis SCDR1 showed high levels of
      resistance against Nanosilver colloids, Nanosilver chitosan composite and the
      commercially available Nanosilver and silver bandages. The P. mirabilis -SCDR1
      genome size is 3,815,621 bp. with G + C content of 38.44%. P. mirabilis-SCDR1
      genome contains a total of 3533 genes, 3414 coding DNA sequence genes, 11, 10, 18
      rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required
      pathogenicity and virulence factors to establish a successful infection. P.
      mirabilis SCDR1 isolate is a potential virulent pathogen that despite its
      original isolation site, the wound, can establish kidney infection and its
      associated complications. P. mirabilis SCDR1 contains several mechanisms for
      antibiotics and metals resistance, including, biofilm formation, swarming
      mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis
      SCDR1 is the first reported spontaneous Nanosilver resistant bacterial strain. P.
      mirabilis SCDR1 possesses several mechanisms that may lead to the observed
      Nanosilver resistance.

PMID- 29204275
TI  - Fractography of clinically fractured, implant-supported dental computer-aided
      design and computer-aided manufacturing crowns.
AB  - Today, a substantial part of the dental crown production uses computer-aided
      design and computer-aided manufacturing (CAD/CAM) technology. A recent step in
      restorative dentistry is the replacement of natural tooth structure with pre
      polymerized and machined resin-based methacrylic polymers. Recently, a new
      CAD/CAM composite was launched for the crown indication in the load-bearing area,
      but the clinical reality forced the manufacturer to withdraw this specific
      indication. In parallel, a randomized clinical trial of CAD/CAM composite crowns
      luted on zirconia implant abutments revealed a high incidence of failure within
      the first year of service. Fractured crowns of this clinical trial were retrieved
      and submitted to a fractographic examination. The aim of the case series
      presented in this article was to identify failure reasons for a new type of
      CAD/CAM composite crown material (Lava Ultimate; 3M Oral Care, St. Paul,
      Minnesota, USA) via fractographic examinations and analytical assessment of
      luting surfaces and water absorption behavior. As a result, the debonding of the
      composite crowns from the zirconia implant abutments was identified as the
      central reason for failure. The adhesive interface was found the weakest link. A
      lack of silica at the zirconia surface certainly has compromised the bonding
      potential of the adhesive system from the beginning. Additionally, the hydrolytic
      stress released from swelling of the resin-based crown (water absorption) and
      transfer to the luting interface further added to the interfacial stress and most
      probably contributed to a great extend to the debonding failure.

PMID- 29204276
TI  - The mediating role of mentalizing capacity between parents and peer attachment
      and adolescent borderline personality disorder.
AB  - Background: Insecure attachment is a precursor and correlate of borderline
      personality disorder. According to the mentalization-based theory of borderline
      personality disorder, the presence of insecure attachment derails the development
      of the capacity to mentalize, potentially resulting in borderline pathology.
      While one prior study found support for this notion in adolescents, it neglected
      a focus on peer attachment. Separation from primary caregivers and formation of
      stronger bonds to peers are key developmental achievements during adolescence and
      peer attachment warrants attention as a separate concept. Findings: In a cross
      sectional study, female outpatients (Mage 15.78=, SD = 1.04) who fulfilled DSM-5
      criteria for BPD (N = 106) or met at least 4 BPD criteria (N = 4) completed self
      reports on attachment to parents and peers, mentalizing capacity (reflective
      function) and borderline personality features. Our findings suggest that in a
      simple mediational model, mentalizing capacity mediated the relation between
      attachment to peers and borderline features. In the case of attachment to
      parents, the mediational model was not significant. Conclusions: The current
      study is the first to evaluate this mediational model with parent and peer
      attachment as separate concepts and the first to do so in a sample of adolescents
      who meet full or sub-threshold criteria for borderline personality disorder.
      Findings incrementally support that mentalizing capacity and attachment
      insecurity, also in relation to peers, are important concepts in theoretical
      approaches to the development of borderline personality disorder in adolescence.
      Clinical implications are discussed.

PMID- 29204277
TI  - Cytomegalovirus-mononucleosis-induced thyroiditis in an immunocompetent patient.
AB  - : Enteroviruses, including coxsackieviruses and Echovirus, are well known
      pathogens responsible for the development of thyroiditis. We describe the case of
      a 49-year-old woman with no personal or family history of thyroid disease who
      presented to the emergency room with a two-week history of daily fevers up to 39
      degrees C, a sore throat, occasional palpitations and diaphoresis, decreased
      appetite and an unintentional 10 kg weight loss over the same time course
      Physical examination revealed mild tachycardia, an intention tremor and a normal
      sized, nontender thyroid gland without palpable nodules. The remainder of the
      physical examination was unremarkable and without stigmata of Graves' disease.
      Her initial blood tests revealed overt thyrotoxicosis, elevated liver enzymes, an
      elevated C-reactive protein, a negative monospot and a positive CMV IgM antibody.
      Thyroid sonography revealed areas of hypoechogenicity and relatively low
      vascularity. Fine-needle biopsy showed a lymphocytic infiltrate. The patient was
      treated symptomatically with propranolol. On follow-up, the patient became
      euthyroid, and her liver enzymes normalised. Previous cases of CMV-induced
      thyroiditis occurred in immunosuppressed patients. This is the first reported
      case of a CMV-mononucleosis-induced thyroiditis in an immunocompetent adult
      patient and serves as a reminder that viral illnesses are a common cause of
      thyroiditis with abnormal liver enzymes. Learning points: The differential
      diagnosis of thyrotoxicosis with abnormal liver enzymes includes severe
      hyperthyroidism and thyroid storm caused by Graves' disease as well as the
      thyrotoxic phase of a thyroiditis, usually caused by a virus such as
      coxsackievirus or, in this case, cytomegalovirus.Cytomegalovirus appears to be a
      recently recognized causal agent for thyroiditis, both in immunosuppressed and
      immunocompetent patients.Careful follow-up of thyroid function tests in patients
      with thyroiditis allows clinicians to determine if patients' thyroid hormone
      secretion normalizes or if they remain hypothyroid.

PMID- 29204278
TI  - Cured primary hyperparathyroidism after fine-needle aspiration biopsy-induced
      parathyroid disappearance.
AB  - : Spontaneous or fine-needle aspiration (FNAB)-induced remission of primary
      hyperparathyroidism (PHPT) may occur, especially for cystic lesions. However, the
      disease generally relapses over a short time period. We present a case of PHPT
      due to an enlarged hyperfunctioning parathyroid that underwent long-term (almost
      9 years) clinical and ultrasonographic remission after the disappearance of the
      lesion following ultrasound (US)-assisted FNAB. A 67-year-old woman with PHPT
      underwent biochemical and US examinations that confirmed the diagnosis and showed
      a lesion suggestive for parathyroid adenoma or hyperplasia. US-FNAB of the lesion
      confirmed its parathyroid nature by means of elevated levels of parathyroid
      hormone within the needle washing fluid. At the second visit, the patient
      referred slight neck swelling that resolved spontaneously in the days after the
      US-FNAB. At subsequent follow-up, the enlarged parathyroid was not found; it was
      visible neither with US nor with magnetic resonance imaging. Biochemical
      remission persists after 9 years. This is the first reported case of cure of PHPT
      after US-FNAB performed on a hyperfunctioning parathyroid resulting in its
      complete disappearance over a period of 9 years of negative biochemical and
      ultrasonographic follow-up. Learning points: Spontaneous or fine-needle
      aspiration-induced remission of primary hyperparathyroidism can occur.Both
      circumstances may present disease relapse over a variable time period, but
      definite remission is also possible even though long-term periodic follow-up
      should be performed.Parathyroid damage should be ruled out in case of neck
      symptomatology after parathyroid fine-needle aspiration or spontaneous
      symptomatology in patients with history of primary hyperparathyroidism.

PMID- 29204279
TI  - Sellar plasmacytoma presenting with symptoms of anterior pituitary dysfunction.
AB  - : Sellar plasmacytomas are rare and the differential diagnosis with non
      functioning pituitary adenomas might be difficult because of clinical and
      radiological resemblance. They usually present with neurological signs and intact
      anterior pituitary function. Some may already have or eventually progress to
      multiple myeloma. We describe a case associated with extensive anterior pituitary
      involvement, which is a rare form of presentation. A 68-year-old man was referred
      to our Endocrinology outpatient clinic due to gynecomastia, reduced libido and
      sexual impotence. Physical examination, breast ultrasound and mammography
      confirmed bilateral gynecomastia. Blood tests revealed slight hyperprolactinemia,
      low testosterone levels, low cortisol levels and central hypothyroidism. Sellar
      MRI showed a heterogeneous sellar mass (56 * 60 * 61 mm), initially suspected as
      an invasive macroadenoma. After correcting the pituitary deficits with
      hydrocortisone and levothyroxine, the patient underwent transsphenoidal surgery.
      Histological examination revealed a plasmacytoma and multiple myeloma was ruled
      out. The patient was unsuccessfully treated with radiation therapy (no tumor
      shrinkage). Myeloma ultimately developed, with several other similar lesions in
      different locations. The patient was started on chemotherapy, had a bone marrow
      transplant and is now stable (progression free) on lenalidomide and
      dexamethasone. The presenting symptoms and panhypopituitarism persisted,
      requiring chronic replacement treatment with levothyroxine, hydrocortisone and
      testosterone. Learning points: Plasmacytomas, although rare, are a possible type
      of sellar masses, which have a completely different treatment approach, so it is
      important to make the correct diagnosis.Usually, they present with neurological
      signs and symptoms and a well-preserved pituitary function, but our case shows
      that anterior pituitary function can be severely compromised.Making a more
      extensive evaluation (clinical and biochemical) might provide some clues to this
      diagnosis.

PMID- 29204281
TI  - 'Lactobacillus raoultii' sp. nov., a new bacterium isolated from the vaginal
      flora of a woman with bacterial vaginosis.
AB  - We report the isolation of a new bacterium species, 'Lactobacillus raoultii'
      strain Marseille P4006 (CSUR P4006), isolated from a vaginal sample of a 45-year
      old woman with bacterial vaginosis.

PMID- 29204280
TI  - Physical fitness and levels of physical activity in people with severe mental
      illness: a cross-sectional study.
AB  - Background: Physical fitness is a crucial variable in people with severe mental
      illness as these people could be more independent and improve their job
      opportunities. The present study compared the physical fitness of physically
      active and inactive people with severe mental illness. Methods: Physical fitness
      was evaluated in sixty-two people with severe mental illness using 11 physical
      tests that include strength, flexibility, balance and aerobic condition.
      Significant differences were found between both groups in muscle strength
      (handgrip test) and balance (single leg balance test and functional reach) with
      better performance in the group of physically active people. Results: The results
      of the present study suggest that physical fitness (strength and balance) is
      higher in people with severe mental illness who practise regular physical
      activity that those who are inactive people. Conclusions: Physical active people
      may have a reduced risk of falls and fractures due to their higher levels of
      physical fitness.

PMID- 29204282
TI  - In vivo selection of a multidrug-resistant Aeromonas salmonicida during medicinal
      leech therapy.
AB  - We report the selection in a 15-year-old boy of a multidrug-resistant, extended
      spectrum beta-lactamase (ESBL)-producing Aeromonas salmonicida after medicinal
      leech therapy that required an antibiotic prophylaxis based on
      piperacillin/tazobactam and cotrimoxazole. Whole genome sequencing of the strain
      indeed revealed 13 antibiotic resistance genes, including the ESBL CTX-M-3 and
      the unusual beta-lactamase SCO-1.

PMID- 29204283
TI  - Genome sequence of "Leucobacter massiliensis" sp. nov. isolated from human
      pharynx after travel to the 2014 Hajj.
AB  - "Leucobacter massiliensis" strain 122RC15T sp. nov. is a new species within the
      genus Leucobacter. The genome of this strain is described here. It was isolated
      from the pharynx of a 76-year-old Algerian female after travelling from the 2014
      Hajj. "Leucobacter massiliensis" is a Gram-positive, aerobic bacillus. Here we
      describe the features including complete genome and annotation of this strain.
      The 3 136 406-bp long genome contains 2797 protein-coding genes and 49 RNA genes.

PMID- 29204284
TI  - 'Brevibacterium ihuae' sp. nov., isolated from a stool sample of a healthy 25
      year-old woman.
AB  - We report the main characteristics of 'Brevibacterium ihuae' strain cv3T isolated
      from a stool sample of a healthy 25-year-old woman.

PMID- 29204285
TI  - Molecular characterization of Acinetobacter baumannii isolated from Iraqi
      hospital environment.
AB  - Healthcare-associated items are a common source of acquired infections, and
      hospital-acquired infections cause significant mortality and morbidity worldwide.
      Acinetobacter baumannii is the most prevalent infection-causing organism in the
      hospital environment. Hospital articles and objects are the main sources of
      infection with the ability to transmit some of the pathogenic microorganisms such
      as A. baumannii, which is considered a serious problem in therapeutic treatments.
      In the current study, we isolated A. baumannii from hospital sources and
      evaluated its antibiotic resistance, virulence factors and resistance gene
      determinants. The isolates were identified phenotypically as well as
      genotypically using PCR. In addition, their capability for biofilm formation and
      ten other virulence factors were measured. Of 112 samples, 21 showed growth of
      the target organism. Apart from A. baumannii, isolates of Candida albicans,
      Staphylococcus sp., Pseudomonas aeruginosa, Escherichia coli and Klebsiella
      pneumoniae were also grown. Antibiotic susceptibility test results considered all
      the A. baumannii to be multidrug-resistant isolates with the highest resistance
      being 100% to gentamycin, ciprofloxacin; the most effective antibiotics with 100%
      susceptibility was colistin and tigecycline. All A. baumannii isolates had MIC
      for ceftriaxone >32 mg/L. All A. baumannii isolates from the hospital environment
      showed multidrug resistance and had many virulence factors. They have long-term
      resistance to dry conditions and cause a serious public health issue.

PMID- 29204286
TI  - Accurate differentiation of Escherichia coli and Shigella serogroups: challenges
      and strategies.
AB  - Shigella spp. and Escherichia coli are closely related; both belong to the family
      Enterobacteriaceae. Phenotypically, Shigella spp. and E. coli share many common
      characteristics, yet they have separate entities in epidemiology and clinical
      disease, which poses a diagnostic challenge. We collated information for the best
      possible approach to differentiate clinically relevant E. coli from Shigella spp.
      We found that a molecular approach is required for confirmation. High
      discriminatory potential is seen with whole genome sequencing analysed for k-mers
      and single nucleotide polymorphism. Among these, identification using single
      nucleotide polymorphism is easy to perform and analyse, and it thus appears more
      promising. Among the nonmolecular methods, matrix-assisted desorption ionization
      time of flight mass spectrometry may be applicable when data analysis is assisted
      with advanced analytic tools.

PMID- 29204287
TI  - Libanicoccus massiliensis gen. nov., sp. nov., a new bacterium isolated from
      human stool.
AB  - Strain Marseille-P3237 was isolated from a stool sample of a healthy 35-year-old
      Congolese pygmy female. This anaerobic, Gram-negative, non-spore-forming and non
      motile coccus-shaped bacterium is a member of the order Coriobacteriales. It
      exhibits a 2 009 306-bp genome with a 65.46 mol% G+C content and is closely
      related to, but distinct from, members of the Olsenella genus. We propose the
      creation of the new genus Libanicoccus gen. nov. and of the new species
      Libanicoccus massiliensis sp. nov.

PMID- 29204288
TI  - Potency of cashew nut shell liquid in rumen modulation under different dietary
      conditions and indication of its surfactant action against rumen bacteria.
AB  - Background: Cashew nut shell liquid (CNSL) is an agricultural byproduct
      containing alkylphenols that has been shown to favorably change the rumen
      fermentation pattern only under experimentally fixed feeding conditions.
      Investigation of CNSL potency in rumen modulation under a variety of feeding
      regimens, and evidence leading to the understanding of CNSL action are obviously
      necessary for further CNSL applications. The objective of this study was to
      evaluate the potency of CNSL for rumen modulation under different dietary
      conditions, and to visually demonstrate its surfactant action against selected
      rumen bacteria. Methods: Batch culture studies were carried out using various
      diets with 5 different forage to concentrate (F:C) ratios (9:1, 7:3, 5:5. 3:7 and
      1:9). Strained rumen fluid was diluted with a buffer and incubated with each
      diet. Gas and short chain fatty acid (SCFA) profiles were characterized after 18
      h incubation at 39  degrees C. Monensin was also evaluated as a reference
      additive under the same conditions. Four species of rumen bacteria were grown in
      pure culture and exposed to CNSL to determine their morphological sensitivity to
      the surfactant action of CNSL. Results: CNSL supplementation decreased total gas
      production in diets with 5:5 and 3:7 F:C ratios, whereas the F:C ratio alone did
      not affect any gas production. Methane decrease by CNSL addition was more
      apparent in diets with 5:5, 3:7, and 1:9 F:C ratios. An interactive effect of
      CNSL and the F:C ratio was also observed for methane production. CNSL
      supplementation enhanced propionate production, while total SCFA production was
      not affected. Monensin decreased methane production but only in a diet with a 1:9
      F:C ratio with increased propionate. Studies of pure cultures indicated that CNSL
      damaged the cell surface of hydrogen- and formate-producing bacteria, but did not
      change that of propionate-producing bacteria. Conclusion: CNSL can selectively
      inhibit rumen bacteria through its surfactant action to lead fermentation toward
      less methane and more propionate production. As CNSL is effective over a wider
      range of dietary conditions for such modulation of rumen fermentation in
      comparison with monensin, this new additive candidate might be applied to
      ruminant animals for various production purposes and at various stages.

PMID- 29204289
TI  - Successful treatment of tracheal lymphoma in a Siamese cat.
AB  - Case summary: An 8-year-old female spayed Siamese indoor cat presented with a 3
      week history of inspiratory dyspnoea, stridor and open-mouth breathing after
      exercise. Laryngoscopy, tracheoscopy, bronchoscopy and retroflexed
      nasopharyngoscopy were performed, and identified a multilobulated intraluminal
      mass within the trachea. Brush cytology was performed on the mass but was
      inconclusive in providing a definitive diagnosis. A CT scan of the neck failed to
      identify an obvious intraluminal mass and was negative to contrast uptake.
      Surgery was performed and seven rings of the trachea were removed to enable the
      complete excision of the mass. Histopathology of the excised mass was consistent
      with B cell lymphoma. After surgery, chemotherapy treatment was started. At the
      time of writing, 20 months since diagnosis, the cat remained clinically well,
      with no clinical signs or recurrence of macroscopic disease on endoscopic
      evaluation. Relevance and novel information: Upper airway endoscopy was
      considered to be an essential diagnostic tool in this case presenting with signs
      of upper respiratory dyspnoea. Moreover, combined surgery and chemotherapy were
      considered effective treatments and positively affected the long-term prognosis
      of this patient.

PMID- 29204290
TI  - Meningeal carcinomatosis and spinal cord infiltration caused by a locally
      invasive pulmonary adenocarcinoma in a cat.
AB  - Case summary: A 12-year-old domestic shorthair cat was presented with acute non
      painful hindlimb proprioceptive ataxia localising to T3-L3 spinal cord segments.
      MRI revealed paravertebral muscular hyperintensity on T2-weighted images at the
      level of T7-T8 vertebrae. The cat improved on conservative management but
      deteriorated 3 months later. Repeated MRI showed meningeal enhancement at the
      same level and hyperintensity of the paravertebral musculature extending to the
      right thoracic wall and pleural space on short tau inversion recovery images.
      Thoracic CT showed mineralised lesions of the right lung, restricted pleural
      effusion and expansile bone lesions affecting multiple ribs. The cat had been
      treated for pyothorax 5 years earlier but manifested no current respiratory
      signs. Cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis but
      no neoplastic cells. Biopsy of the affected muscles and cytology of the lung and
      pleural lesions suggested a malignant epithelial cell tumour. Post-mortem
      examination confirmed a pulmonary adenocarcinoma locally infiltrating the
      thoracic wall, T7-T8 vertebrae and the spinal cord white matter. Meningeal
      carcinomatosis was detected with neoplastic cells invading the ventral median
      fissure of the spinal cord. No metastases were observed in other organs,
      indicating that neoplastic cells reached the spinal cord by direct extension.
      Relevance and novel information: Spinal meningeal carcinomatosis has not been
      reported in dogs or cats with extraneural tumours but is a well-recognised
      condition in humans. A metastatic cause of meningeal enhancement should be
      considered in patients with neurological signs of unknown origin. Imaging
      findings and CSF results can be non-specific.

PMID- 29204291
TI  - Antibody response against HERV-W env surface peptides differentiates multiple
      sclerosis and neuromyelitis optica spectrum disorder.
AB  - Background: A specific humoral immune response against HERV-W envelope surface
      (env-su) glycoprotein antigens has been reported in serum of patients with
      multiple sclerosis (MS). However, it has not been evaluated to date in patients
      with neuromyelitis optica spectrum disorder (NMOSD). Objective: The objective of
      this paper is to investigate whether antibody (Ab) response against HERV-W env-su
      antigenic peptides differs between NMOSD and MS. Methods: Serum samples were
      collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control
      individuals (HCs). An indirect ELISA was set up to detect specific Abs against
      HERV-W env-su peptides. Results: Our data showed that two antigenic peptides,
      particularly HERV-Wenv93-108 and HERV-Wenv248-262, were statistically
      significantly present only in serum of MS compared to NMOSD and HCs. Thus, the
      specific humoral immune response against HERV-W env-su glycoprotein antigens
      found in MS is widely missing in NMOSD. Conclusion: Increased circulating serum
      levels of these HERV-W Abs may be suitable as additional biomarkers to better
      differentiate MS from NMOSD.

PMID- 29204292
TI  - Serum Neurofilament Light Chain in NMOSD and Related Disorders: Comparison
      According to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies
      Status.
AB  - Background: Neurofilament light chain (NF-L) levels reflect axonal damage in
      different conditions, including demyelinating disorders. Objectives: We aimed to
      compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab),
      myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with
      neuromyelitis optica spectrum disorders and related disorders. Methods: We
      analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive
      electrochemiluminescence immunoassay. Results: Median NF-L levels were increased
      in 25 AQP4-Ab-positive patients (59 pg/ml) as compared with 22 MOG-Ab-positive
      cases (25 pg/ml), 52 seronegative patients (18 pg/ml), 25 multiple sclerosis
      patients (12 pg/ml) and 14 healthy controls (12 pg/ml). Conclusions: Increased
      serum levels of NF-L in patients with AQP4-Ab or MOG-Ab might reflect an ongoing
      axonal damage and a more malignant disease course.

PMID- 29204294
TI  - Corrigendum to "Plant MicroRNA Prediction by Supervised Machine Learning Using
      C5.0 Decision Trees".
AB  - [This corrects the article DOI: 10.1155/2012/652979.].

PMID- 29204293
TI  - Validity, reliability and feasibility of commercially available activity trackers
      in physical therapy for people with a chronic disease: a study protocol of a
      mixed methods research.
AB  - Background: For older people and people with a chronic disease, physical activity
      provides health benefits. Patients and healthcare professionals can use
      commercially available activity trackers to objectively monitor (alterations in)
      activity levels and patterns and to support physical activity. However, insight
      in the validity, reliability, and feasibility of these trackers in people with a
      chronic disease is needed. In this article, a study protocol is described in
      which the validity, reliability (part A), and feasibility from a patient and
      therapist's point of view (part B) of commercially available activity trackers in
      daily life and health care is investigated. Methods: In part A, a quantitative
      cross-sectional study, an activity protocol that simulates everyday life
      activities will be used to determine the validity and reliability of nine
      commercially available activity trackers. Video recordings will act as the gold
      standard. In part B, a qualitative participatory action research study will be
      performed to gain insight in the use of activity trackers in peoples' daily life
      and therapy settings. Objective feasibility of the activity trackers will be
      measured with questionnaires, and subjective feasibility (experiences) will be
      explored in a community of practice. Physical therapists (n = 8) will regularly
      meet during 6 months to learn from each other regarding the actual use of
      activity trackers in therapy. Therapists and patients (n = 48) will decide
      together which tracker will be used in therapy and for which purpose (e.g.,
      monitoring, goal setting). Data from the therapist' and patients' experiences
      will be collected by interviews (individual and focus groups) and analyzed by a
      directed content analysis. At the time of submission, selection of activity
      trackers, development of the activity protocol, and the ethical approval process
      are finished. Data collection and data processing are ongoing. Discussion: The
      relevance of the study as well as the advantages and disadvantages of several
      aspects of the chosen design are discussed. The results acquired from both study
      parts can be used to create decision aids that may assist therapists and people
      with a chronic disease in choosing a suitable activity tracker, and to facilitate
      use of these activity trackers in health care settings. Trial registration:
      Ethical approval has been obtained from two medical-ethical committees (nr. 15-N
      109, 15-N-48 and MEC-15-07).

PMID- 29204295
TI  - Associations of Mitochondrial Fatty Acid Oxidation with Body Fat in Premenopausal
      Women.
AB  - Higher in vivo fatty acid (FA) oxidation rates have been reported in obese
      individuals compared to lean counterparts; however whether this reflects a shift
      in substrate-specific oxidative capacity at the level of the skeletal muscle
      mitochondria has not been examined. The purpose of this study was to test the
      hypothesis that in situ measures of skeletal muscle mitochondria FA oxidation
      would be positively associated with total body fat. Participants were 38
      premenopausal women (BMI = 26.5 +/- 4.3 kg/m2). Total and regional fat were
      assessed by dual-energy X-ray absorptiometry (DXA). Mitochondrial FA oxidation
      was assessed in permeabilized myofibers using high-resolution respirometry and a
      palmitoyl carnitine substrate. We found positive associations of total fat mass
      with State 3 (ADP-stimulated respiration) (r = 0.379, p < 0.05) and the
      respiratory control ratio (RCR, measure of mitochondrial coupling) (r = 0.348, p
      < 0.05). When participants were dichotomized by high or low body fat percent,
      participants with high total body fat displayed a higher RCR compared to those
      with low body fat (p < 0.05). There were no associations between any measure of
      regional fat and mitochondrial FA oxidation independent of total fat mass. In
      conclusion, greater FA oxidation in obesity may reflect molecular processes that
      enhance FA oxidation capacity at the mitochondrial level.

PMID- 29204296
TI  - Quality of Life of People Living with HIV/AIDS in the Ho Municipality, Ghana: A
      Cross-Sectional Study.
AB  - Quality of life (QoL) is an important component in the evaluation of the
      wellbeing of people living with HIV/AIDS (PLHIV). This study was aimed at
      evaluating the QoL of PLHIV attending the antiretroviral clinics in the Ho
      municipality. A cross-sectional study was conducted from January 2017 to April
      2017 involving 158 purposively selected HIV-positive patients who were attending
      the antiretroviral clinics both in the Volta Regional Hospital and Ho Municipal
      Hospital. An Interviewer administered standard questionnaire (WHOQOL-HIV Bref)
      was used to collect information on sociodemography, medical history, and the
      quality of life (QoL) of the respondents. Among these 158 HIV-positive
      respondents, 126 (79.75) and 14 (8.86) presented with excellent and good overall
      QoL, respectively, whilst 18 (11.39) had their life negatively affected by
      HIV/AIDS. Religious/personal beliefs (19.62%) were the most affected QoL
      component, followed by the physical (15.82%) and level of independence (15.19%)
      domains. Patients' occupation, perception of health, sexual activity, and state
      of the disease were associated with poor overall QoL. In general, being an HIV
      infected man, symptomatic patient, not being sexually active, or being ART naive
      was also associated with poorer QoL in several HIV/AIDS QoL domains.

PMID- 29204297
TI  - Which Environmental Factor Is Correlated with Long-Term Multiple Sclerosis
      Incidence Trends: Ultraviolet B Radiation or Geomagnetic Disturbances?
AB  - Background: Insufficient received ultraviolet B radiation (UV) is regarded as the
      main environmental risk factor (RF) for MS in vitamin D deficiency hypothesis.
      Nevertheless, geomagnetic disturbance (GMD) has also been proposed as a potential
      trigger for MS in GMD hypothesis. The aim of this study was to investigate which
      of these mentioned RF is correlated with long-term ultradecadal MS incidence.
      Methods: After a systematic search, long-term incidence reports of the United
      Kingdom (UK), Denmark, Tayside County, Nordland County, the Orkney, and Shetland
      Islands were selected for this retrospective time-series study. Possible lead-lag
      relationships between MS incidence, GMD, and UV were evaluated by cross
      correlation analysis. Results: Significant positive correlations between GMD and
      MS incidence were seen in Tayside County (at lag of 2 years: rS = 0.38), Denmark
      (peak correlation at lag of 2 years: rS = 0.53), and UK (at lag of 1 year: rS =
      0.50). We found a positive correlation between received UV and MS incidences in
      the Nordland at lag of 1 year (rS = 0.49). Conclusion: This study found
      significant positive correlations between alterations in GMD with alterations in
      long-term MS incidence in three out of six studied locations and supports the GMD
      hypothesis. The observed significant correlation between MS and UV is positive;
      hence it is not supportive for UV related vitamin D deficiency hypothesis.

PMID- 29204298
TI  - Treadmill Exercise Improves Motor Dysfunction and Hyperactivity of the
      Corticostriatal Glutamatergic Pathway in Rats with 6-OHDA-Induced Parkinson's
      Disease.
AB  - Hyperactivity in the corticostriatal glutamatergic pathway (CGP) induces basal
      ganglia dysfunction, contributing to parkinsonian syndrome (PS). Physical
      exercise can improve PS. However, the effect of exercise on the CGP, and whether
      this pathway is involved in the improvement of PS, remains unclear. Parkinson's
      disease (PD) was induced in rats by 6-hydroxydopamine injection into the right
      medial forebrain bundle. Motor function was assessed using the cylinder test.
      Striatal neuron (SN) spontaneous and evoked firing activity was recorded, and the
      expression levels of Cav1.3 and CaMKII in the striatum were measured after 4
      weeks of treadmill exercise. The motor function in PD rats was improved by
      treadmill exercise. SN showed significantly enhanced excitability, and treadmill
      exercise reduced SN excitability in PD rats. In addition, firing activity was
      evoked in SNs by stimulation of the primary motor cortex, and SNs exhibited
      significantly decreased stimulus threshold, increased firing rates, and reduced
      latency. The expression of Cav1.3 and p-CaMKII (Thr286) in the striatum were
      enhanced in PD rats. However, these effects were reversed by treadmill exercise.
      These findings suggest that treadmill exercise inhibits CGP hyperactivity in PD
      rats, which may be related to improvement of PS.

PMID- 29204299
TI  - Diabetes Mellitus Secondary to Acute Pancreatitis in a Child with Wolf-Hirschhorn
      Syndrome.
AB  - Wolf-Hirschhorn Syndrome (WHS) is a rare genetic disease caused by deletion in
      the short arm of chromosome 4. It is characterized by typical fascial features
      and a varying degree of intellectual disabilities and multiple systemic
      involvement. Epidemiological studies confirmed the association of acute
      pancreatitis with the development of diabetes. However, this association has not
      been reported in WHS. We report an 18-year-old girl with WHS who presented
      acutely with nonketotic Hyperglycemic Hyperosmolar Status (HHS) in association
      with severe acute pancreatitis. Her presentation was preceded by febrile illness
      with preauricular abscess. She was treated with fluids and insulin infusion and
      remained on insulin 18 months after presentation. Her parents are cousins and the
      mother was diagnosed with type 2 diabetes. She had negative autoantibodies and no
      signs of insulin resistance and her monogenic diabetes genetic testing was
      negative. Microarray study using WHS probe confirmed deletion of 4p chromosome.
      Acute pancreatitis is uncommon in children and development of diabetes following
      pancreatitis has not been reported in WHS. HHS is considerably less frequent than
      diabetes ketoacidosis in children. We highlight the complex presentation with HHS
      and acute pancreatitis leading to diabetes that required long term of insulin
      treatment.

PMID- 29204300
TI  - Yogi Detox Tea: A Potential Cause of Acute Liver Failure.
AB  - We present a case of acute fulminant liver failure from a liver detoxification
      tea. We present a 60-year-old female with weakness, lethargy, scleral icterus,
      jaundice, and worsening mental status. She drank herbal tea three times a day for
      14 days prior to symptom development. Liver tests were elevated. Remaining
      laboratory tests and imaging were negative for other etiologies. An ultrasound
      guided liver biopsy showed submassive necrosis. A literature search on the
      ingredients shows six ingredients as having hepatotoxic effects and remaining
      ingredients as having very sparse hepatoprotective data. Healthcare professionals
      should discuss herbal medication and tea use and report adverse effects.

PMID- 29204301
TI  - Human Infection with Fusobacterium necrophorum without Jugular Venous Thrombosis:
      A Varied Presentation of Lemierre's Syndrome.
AB  - Lemierre's syndrome is also known as postangina septicemia, which is commonly
      caused by Fusobacterium necrophorum also known as Necrobacillus and also by other
      microorganisms like Staphylococcus, Streptococcus, Peptostreptococcus, and
      Bacteroides. Though the disease starts as an upper respiratory tract infection,
      it may spread and cause thrombophlebitis of the internal jugular vein. It may
      present itself through cranial nerve palsy or sepsis involving distant organs
      like the lungs or bones. It is also known as forgotten disease because of its
      rarity. Fusobacterium necrophorum usually causes infection in animals and rarely
      affects humans. We hereby present a case of Necrobacillus infection which did not
      cause any thrombophlebitis but resulted in severe pneumonia and acute kidney
      injury, leading to respiratory failure and requiring mechanical ventilation.

PMID- 29204302
TI  - Parainfluenza 3 Respiratory Infection Associated with Pericardial Effusion in a
      Very Low Birthweight Infant.
AB  - Parainfluenza 3 virus is a frequent cause of respiratory infections in the
      pediatric population although it is uncommonly diagnosed in neonates, being
      usually reported as neonatal intensive care unit microepidemics. We report a case
      of parainfluenza 3 respiratory infection associated with pericardial effusion in
      a very low birthweight infant.

PMID- 29204303
TI  - Maxillary Sinus Kaposi Sarcoma: Case Report in an HIV-Negative Patient with
      Thymoma.
AB  - Introduction: Kaposi sarcoma is an angioproliferative disorder that requires
      infection with human herpesvirus 8 (HHV-8) for its development. The majority of
      cases are associated with HIV infection or other immunocompromising conditions.
      Thymomas are occasionally associated to cytopenia, which may alter the patients'
      immune responses. Methods: Case report using clinical records. Results: Case
      report of a 46-year-old male patient diagnosed with thymoma and myasthenia
      gravis. The patient was referred to an otolaryngology consultation with
      complaints of facial pain in the right malar region, interpreted as an acute
      sinusitis. Following examination, an expansive maxillary sinus mass was found,
      and endoscopic surgery was undertaken. After careful investigation, it was
      diagnosed as a Kaposi sarcoma. Conclusions: It is thought to be the first
      described case of a maxillary sinus Kaposi sarcoma in an HIV-negative patient.
      Thus, this entity has to be considered in the differential diagnosis of sinus
      masses, even in non-HIV patients.

PMID- 29204304
TI  - Langerhans Cell Histiocytosis: A Diagnostic Challenge in the Oral Cavity.
AB  - Background: Langerhans cell histiocytosis (LCH) is a rare disorder of the
      reticuloendothelial system with unknown etiology. This report aims to present a
      case of LCH with diffuse involvement of the oral cavity and to raise awareness of
      the distinguishing features of this diagnostically challenging entity. Case
      Report: A 26-year-old male patient presented with complaints of teeth mobility,
      intense pain, and difficulty in chewing. Intraoral and radiological examinations
      revealed generalized gingival hyperplasia and severe teeth mobility with
      widespread alveolar bone loss. Periodontal therapy was performed with no
      significant improvement. An incisional biopsy revealed Langerhans cells and
      positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The
      patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids.
      Regression of gingival lesions, as well as significant decrease in mobility of
      the remaining teeth and severity of pain, was achieved during 12 months of follow
      up. Conclusion: The rarity and variable system involvement of LCH necessitate a
      multidisciplinary approach be carried out for accurate diagnosis, effective
      treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH
      may aid clinicians greatly in reducing morbidity and mortality associated with
      this debilitating condition.

PMID- 29204306
TI  - Facial palsy after embolization of dural arteriovenous fistula: A case report and
      literature review.
AB  - Background: Dural arteriovenous fistulas (DAVF) are unusual intracranial vascular
      malformations consisting of anomalous connections between meningeal arteries and
      dural sinuses or the veins that pass through them. They have variable clinical
      presentation and prognosis, which depend on their location and venous
      hemodynamics. Treatment is based on the closure of the abnormal connections,
      which is usually conducted via arterial and/or transvenous endovascular
      techniques. Case Description: We present a male patient who complained of
      headaches and left-sided pulsatile tinnitus due to DAVF from the external carotid
      artery branches draining directly into the ipsilateral sigmoid sinus.
      Embolization with Onyx(r) was successful, obtaining angiographic occlusion and
      symptom remission. However, on postoperative day 4, the patient presented with
      left facial palsy and spontaneous regression. Conclusion: Although embolization
      is an effective and safe procedure, complications may occur. Reflux of the
      embolic agent to the vasa nervorum of the cranial nerve may lead to ischemic
      neuropathy. Here, we reported a case of embolized DAVF presenting with a
      postoperative peripheral facial palsy where the two embolized pedicles were
      branches of the middle meningeal and occipital arteries involved in the
      vascularization of the extratemporal segment of the facial nerve. We discuss the
      etiopathogenic, anatomical, and pathophysiological aspects of this complication.

PMID- 29204305
TI  - Ethanol-Induced White Matter Atrophy Is Associated with Impaired Expression of
      Aspartyl-Asparaginyl-beta-Hydroxylase (ASPH) and Notch Signaling in an
      Experimental Rat Model.
AB  - Alcohol-induced white matter (WM) degeneration is linked to cognitive-motor
      deficits and impairs insulin/insulin-like growth factor (IGF) and Notch networks
      regulating oligodendrocyte function. Ethanol downregulates Aspartyl-Asparaginyl
      beta-Hydroxylase (ASPH) which drives Notch. These experiments determined if
      alcohol-related WM degeneration was linked to inhibition of ASPH and Notch. Adult
      Long Evans rats were fed for 3, 6 or 8 weeks with liquid diets containing 26%
      ethanol (caloric) and in the last two weeks prior to each endpoint they were
      binged with 2 g/kg ethanol, 3*/week. Controls were studied in parallel.
      Histological sections of the frontal lobe and cerebellar vermis were used for
      image analysis. Frontal WM proteins were used for Western blotting and duplex
      ELISAs. The ethanol exposures caused progressive reductions in frontal and
      cerebellar WM. Ethanol-mediated frontal WM atrophy was associated with reduced
      expression of ASPH, Jagged 1, HES-1, and HIF-1alpha. These findings link ethanol
      induced WM atrophy to inhibition of ASPH expression and signaling through Notch
      networks, including HIF-1alpha.

PMID- 29204307
TI  - Treatment of intracerebellar haemorrhage: Poor outcome and high long-term
      mortality.
AB  - Background: Intracerebellar haemorrhage constitutes around 10% of all
      spontaneous, non-aneurysmal intracerebral haemorrhages (ICHs) and often carries a
      grim prognosis. In symptomatic patients, surgical evacuation is usually regarded
      the standard treatment. Our objective was to compare the in-hospital mortality
      and functional outcome at hospital discharge in either medically or surgically
      treated patients, and the impact of either treatment on long-term mortality after
      a cerebellar ICH. Methods: An observational, retrospective, single-centre
      consecutive series of 114 patients with cerebellar ICH. We assessed the effect of
      different demographic factors on functional outcome and in-hospital mortality
      using logistic regression. We also divided the patients in medical and surgical
      treatment groups based on how they had been treated and compared the clinical and
      radiological parameters, in-hospital, and long-term mortality in the different
      groups. Results: In our series, 38 patients (33.3%) underwent haematoma
      evacuation and 76 (66.7%) received medical treatment. Glasgow coma scale <8,
      blocked quadrigeminal cistern, and severe hydrocephalus were associated with in
      hospital death or poor functional outcome at discharge (modified Rankin scale 4
      6). Surgically treated patients were younger, had larger haematomas both in
      volume and diameter, were in a worse clinical condition, and suffered more from
      hydrocephalus and brainstem compression. There were no statistically significant
      differences in in-hospital or long-term mortality. However, the surgically
      treated patients remained in a poor clinical condition. Conclusions: Surgical
      treatment of cerebellar ICH can be life-saving but often leads to a poor
      functional outcome. New studies are needed on long-term functional outcome after
      a cerebellar ICH.

PMID- 29204308
TI  - Aplasia cutis congenita: Two case reports and discussion of the literature.
AB  - Background: Aplasia cutis congenita (ACC) is a part of a heterogeneous group of
      conditions characterized by the congenital absence of epidermis, dermis, and in
      some cases, subcutaneous tissues or bone usually involving the scalp vertex.
      There is an estimated incidence of 3 in 10,000 births resulting in a total number
      of 500 reported cases to date. The lesions may occur on every body surface
      although localized scalp lesions form the most frequent pattern (70%). Complete
      aplasia involving bone defects occurs in approximately 20% of cases. ACC can
      occur as an isolated defect or can be associated with a number of other
      congenital anomalies such as limb anomalies or embryologic malformations. In
      patients with large scalp and skull defects, there is increased risk of infection
      and bleeding along with increased mortality and therefore prompt and effective
      management is advised. Case Description: We describe two cases of ACC, involving
      a 4 * 3 cm defect managed conservatively and a larger 10 * 5 cm defect managed
      surgically with the use of a temporo-occipital scalp flap. Both cases had an
      excellent outcome. Conclusions: Multiple treatment regimens exist for ACC, but
      there is no consensus on treatment strategies. Conservative treatment has been
      described and advocated, but many authors have emphasized the disadvantages of
      this treatment modality. Decision between conservative and surgical management
      must be individualized according to lesion size and location.

PMID- 29204310
TI  - Laser-emission imaging of nuclear biomarkers for high-contrast cancer screening
      and immunodiagnosis.
AB  - Detection of nuclear biomarkers such as nucleic acids and nuclear proteins is
      critical for early-stage cancer diagnosis and prognosis. Conventional methods
      relying on morphological assessment of cell nuclei in histopathology slides may
      be subjective, whereas colorimetric immunohistochemical and fluorescence-based
      imaging are limited by strong light absorption, broad-emission bands and low
      contrast. Here, we describe the development and use of a scanning laser-emission
      based microscope that maps lasing emissions from nuclear biomarkers in human
      tissues. 41 tissue samples from 35 patients labelled with site-specific and
      biomarker-specific antibody-conjugated dyes were sandwiched in a Fabry-Perot
      microcavity while an excitation laser beam built a laser-emission image. We
      observed multiple sub-cellular lasing emissions from cancer cell nuclei, with a
      threshold of tens of MUJ/mm2, sub-micron resolution (<700 nm), and a lasing band
      in the few-nanometre range. Different lasing thresholds of nuclei in cancer and
      normal tissues enabled the identification and multiplexed detection of nuclear
      proteomic biomarkers, with a high sensitivity for early-stage cancer diagnosis.
      Laser-emission-based cancer screening and immunodiagnosis might find use in
      precision medicine and facilitate research in cell biology.

PMID- 29204311
TI  - A polarization-insensitive plasmonic photoconductive terahertz emitter.
AB  - We present a polarization-insensitive plasmonic photoconductive terahertz emitter
      that uses a two-dimensional array of nanoscale cross-shaped apertures as the
      plasmonic contact electrodes. The geometry of the cross-shaped apertures is set
      to maximize optical pump absorption in close proximity to the contact electrodes.
      The two-dimensional symmetry of the cross-shaped apertures offers a polarization
      insensitive interaction between the plasmonic contact electrodes and optical pump
      beam. We experimentally demonstrate a polarization-insensitive terahertz
      radiation from the presented emitter in response to a femtosecond optical pump
      beam and similar terahertz radiation powers compared to previously demonstrated
      polarization-sensitive photoconductive emitters with plasmonic contact electrode
      gratings at the optimum optical pump polarization.

PMID- 29204309
TI  - Laser application in neurosurgery.
AB  - Background: Technological innovations based on light amplification created by
      stimulated emission of radiation (LASER) have been used extensively in the field
      of neurosurgery. Methods: We reviewed the medical literature to identify current
      laser-based technological applications for surgical, diagnostic, and therapeutic
      uses in neurosurgery. Results: Surgical applications of laser technology reported
      in the literature include percutaneous laser ablation of brain tissue, the use of
      surgical lasers in open and endoscopic cranial surgeries, laser-assisted
      microanastomosis, and photodynamic therapy for brain tumors. Laser systems are
      also used for intervertebral disk degeneration treatment, therapeutic
      applications of laser energy for transcranial laser therapy and nerve
      regeneration, and novel diagnostic laser-based technologies (e.g., laser scanning
      endomicroscopy and Raman spectroscopy) that are used for interrogation of
      pathological tissue. Conclusion: Despite controversy over the use of lasers for
      treatment, the surgical application of lasers for minimally invasive procedures
      shows promising results and merits further investigation. Laser-based microscopy
      imaging devices have been developed and miniaturized to be used intraoperatively
      for rapid pathological diagnosis. The multitude of ways that lasers are used in
      neurosurgery and in related neuroclinical situations is a testament to the
      technological advancements and practicality of laser science.

PMID- 29204313
TI  - Dystonic Head Tremor and the Coexistence of Headache.
AB  - Background: Head tremor may be observed in the presence of cervical dystonia and
      sometimes coexists with headache. We wished to investigate the presence of
      headache in dystonic head tremor. Methods: We studied the files of 19 patients
      from our outpatient clinic (1997-2017) with dystonic head tremor and assessed the
      co-occurrence of headache. We also performed a literature search of the topic.
      Results: Cervicogenic headache was present in nearly 37% of patients with
      dystonic head tremor. More than 85% of our patients presented with a "no-no" head
      tremor. Discussion: Headache is common in dystonic head tremor. Cervicogenic
      headache seems to be more frequent in patients with dystonic head tremor than in
      the general population. Future studies should compare the presence of
      cervicogenic headache in essential head tremor patients with that in patients
      suffering from dystonic head tremor.

PMID- 29204312
TI  - Insights into Pathophysiology from Medication-induced Tremor.
AB  - Background: Medication-induced tremor (MIT) is common in clinical practice and
      there are many medications/drugs that can cause or exacerbate tremors. MIT
      typically occurs by enhancement of physiological tremor (EPT), but not all drugs
      cause tremor in this way. In this manuscript, we review how some common examples
      of MIT have informed us about the pathophysiology of tremor. Methods: We
      performed a PubMed literature search for published articles dealing with MIT and
      attempted to identify articles that especially dealt with the medication's
      mechanism of inducing tremor. Results: There is a paucity of literature that
      deals with the mechanisms of MIT, with most manuscripts only describing the
      frequency and clinical settings where MIT is observed. That being said, MIT
      emanates from multiple mechanisms depending on the drug and it often takes an
      individualized approach to manage MIT in a given patient. Discussion: MIT has
      provided some insight into the mechanisms of tremors we see in clinical practice.
      The exact mechanism of MIT is unknown for most medications that cause tremor, but
      it is assumed that in most cases physiological tremor is influenced by these
      medications. Some medications (epinephrine) that cause EPT likely lead to tremor
      by peripheral mechanisms in the muscle (beta-adrenergic agonists), but others may
      influence the central component (amitriptyline). Other drugs can cause tremor,
      presumably by blockade of dopamine receptors in the basal ganglia (dopamine
      blocking agents), by secondary effects such as causing hyperthyroidism
      (amiodarone), or by other mechanisms. We will attempt to discuss what is known
      and unknown about the pathophysiology of the most common MITs.

PMID- 29204314
TI  - The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia:
      Lessons from Magnetoencephalography.
AB  - Background: Pharmacological management of cervical dystonia (CD) is considered to
      be symptomatic in effect, rather than targeting the underlying pathophysiology of
      the disease. Magnetoencephalography (MEG), a direct measure of neuronal activity,
      while accepted as a modality for pre-surgical mapping in epilepsy, has never been
      used to explore the effect of pharmacotherapy in movement disorders. Methods:
      Resting state MEG data were collected from patients with CD, pre- and post
      botulinum toxin injections. All of these patients exhibited good clinical benefit
      with botulinum toxin. Resting state MEG data from four age- and gender-matched
      healthy controls with no neurological disorders were also collected. Results: Our
      exploratory study reveals a difference in coherence between controls and patients
      in the following regions: fronto-striatal, occipito-striatal, parieto-striatal,
      and striato-temporal networks. In these regions there is an increase after
      botulinum toxin. Specifically, increased coherence in the left putamen and right
      superior parietal gyrus was noticeable. Both intrahemispheric and
      interhemispheric networks were affected. Discussion: This is the first attempt to
      directly assess changes in functional connectivity with pharmacotherapy using
      MEG. Botulinum toxin might affect sensorimotor integration, leading to clinical
      benefit. The presence of increased interhemispheric coherence and
      intrahemispheric coherence points to the importance of global and local networks
      in the pathophysiology of dystonia.

PMID- 29204315
TI  - Pathogenesis of Primary Orthostatic Tremor: Current Concepts and Controversies.
AB  - Background: Orthostatic tremor (OT), a rare and complex movement disorder, is
      characterized by rapid tremor of both legs and the trunk while standing. These
      disappear while the patient is either lying down or walking. OT may be
      idiopathic/primary or it may coexist with several neurological conditions
      (secondary OT/OT plus). Primary OT remains an enigmatic movement disorder and its
      pathogenesis and neural correlates are not fully understood. Methods: A PubMed
      search was conducted in July 2017 to identify articles for this review. Results:
      Structural and functional neuroimaging studies of OT suggest possible alterations
      in the cerebello-thalamo-cortical network. As with essential tremor, the presence
      of a central oscillator has been postulated for OT; however, the location of the
      oscillator within the tremor network remains elusive. Studies have speculated a
      possible dopaminergic deficit in the pathogenesis of primary OT; however, the
      evidence in favor of this concept is not particularly robust. There is also
      limited evidence favoring the concept that primary OT is a neurodegenerative
      disorder, as a magnetic resonance spectroscopic imaging study revealed
      significant reduction in cerebral and cerebellar N-acetyl aspartate (NAA) levels,
      a marker of neuronal compromise or loss. Discussion: Based on the above, it is
      clear that the pathogenesis of primary OT still remains unclear. However, the
      available evidence most strongly favors the existence of a central oscillatory
      network, and involvement of the cerebellum and its connections.

PMID- 29204316
TI  - Acute Dystonic Reaction Following General Anesthetic Agent Use.
AB  - Background: A 36-year-old Thai female who underwent a thymectomy under general
      anesthesia developed acute abnormal movements in the craniofacial region
      immediately after awakening with preserved consciousness. Phenomenology:
      Intermittent abnormal movements included oculogyric crisis; tongue protrusion;
      blepharospasm; and oro-mandibular dystonia consisting of risus sardonicus, jaw
      opening, and right torticollis. Educational value: An acute dystonic reaction can
      be a complication of either single or combined general anesthetic agents.

PMID- 29204317
TI  - BGDMdocker: a Docker workflow for data mining and visualization of bacterial pan
      genomes and biosynthetic gene clusters.
AB  - Recently, Docker technology has received increasing attention throughout the
      bioinformatics community. However, its implementation has not yet been mastered
      by most biologists; accordingly, its application in biological research has been
      limited. In order to popularize this technology in the field of bioinformatics
      and to promote the use of publicly available bioinformatics tools, such as
      Dockerfiles and Images from communities, government sources, and private owners
      in the Docker Hub Registry and other Docker-based resources, we introduce here a
      complete and accurate bioinformatics workflow based on Docker. The present
      workflow enables analysis and visualization of pan-genomes and biosynthetic gene
      clusters of bacteria. This provides a new solution for bioinformatics mining of
      big data from various publicly available biological databases. The present step
      by-step guide creates an integrative workflow through a Dockerfile to allow
      researchers to build their own Image and run Container easily.

PMID- 29204318
TI  - Kullback Leibler divergence in complete bacterial and phage genomes.
AB  - The amino acid content of the proteins encoded by a genome may predict the coding
      potential of that genome and may reflect lifestyle restrictions of the organism.
      Here, we calculated the Kullback-Leibler divergence from the mean amino acid
      content as a metric to compare the amino acid composition for a large set of
      bacterial and phage genome sequences. Using these data, we demonstrate that (i)
      there is a significant difference between amino acid utilization in different
      phylogenetic groups of bacteria and phages; (ii) many of the bacteria with the
      most skewed amino acid utilization profiles, or the bacteria that host phages
      with the most skewed profiles, are endosymbionts or parasites; (iii) the skews in
      the distribution are not restricted to certain metabolic processes but are common
      across all bacterial genomic subsystems; (iv) amino acid utilization profiles
      strongly correlate with GC content in bacterial genomes but very weakly correlate
      with the G+C percent in phage genomes. These findings might be exploited to
      distinguish coding from non-coding sequences in large data sets, such as
      metagenomic sequence libraries, to help in prioritizing subsequent analyses.

PMID- 29204319
TI  - Reference standards to assess physical fitness of children and adolescents of
      Brazil: an approach to the students of the Lake Itaipu region-Brazil.
AB  - Background: The importance of assessing body fat variables and physical fitness
      tests plays an important role in monitoring the level of activity and physical
      fitness of the general population. The objective of this study was to develop
      reference norms to evaluate the physical fitness aptitudes of children and
      adolescents based on age and sex from the lake region of Itaipu, Brazil. Methods:
      A descriptive cross-sectional study was carried out with 5,962 students (2,938
      males and 3,024 females) with an age range of 6.0 and 17.9 years. Weight (kg),
      height (cm), and triceps (mm), and sub-scapular skinfolds (mm) were measured.
      Body Mass Index (BMI kg/m2) was calculated. To evaluate the four physical fitness
      aptitude dimensions (morphological, muscular strength, flexibility, and cardio
      respiratory), the following physical education tests were given to the students:
      sit-and-reach (cm), push-ups (rep), standing long jump (cm), and 20-m shuttle run
      (m). Results and Discussion: Females showed greater flexibility in the sit-and
      reach test and greater body fat than the males. No differences were found in BMI.
      Percentiles were created for the four components for the physical fitness
      aptitudes, BMI, and skinfolds by using the LMS method based on age and sex. The
      proposed reference values may be used for detecting talents and promoting health
      in children and adolescents.

PMID- 29204320
TI  - Hermit crab response to a visual threat is sensitive to looming cues.
AB  - Prior work in our lab has shown that an expanding image on a computer screen
      elicits a hiding response in the Caribbean terrestrial hermit crab (Coenobita
      clypeatus). We conducted two experiments to identify what properties of the
      expanding stimulus contribute to its effectiveness as a visual threat. First we
      found that an expanding geometric star evoked a strong hiding response while a
      contracting or full-sized stationary star did not. A second experiment revealed
      that the more quickly the stimulus expanded the shorter the latency to hide.
      These findings suggest that the anti-predator response to looming stimulus relies
      heavily on visual cues relating to the manner of approach. The simulated visual
      threat on a computer screen captures key features of a real looming object that
      elicits hiding behavior in crabs in the wild.

PMID- 29204321
TI  - Ordinary kriging vs inverse distance weighting: spatial interpolation of the
      sessile community of Madagascar reef, Gulf of Mexico.
AB  - Information about the distribution and abundance of the habitat-forming sessile
      organisms in marine ecosystems is of great importance for conservation and
      natural resource managers. Spatial interpolation methodologies can be useful to
      generate this information from in situ sampling points, especially in
      circumstances where remote sensing methodologies cannot be applied due to small
      scale spatial variability of the natural communities and low light penetration in
      the water column. Interpolation methods are widely used in environmental
      sciences; however, published studies using these methodologies in coral reef
      science are scarce. We compared the accuracy of the two most commonly used
      interpolation methods in all disciplines, inverse distance weighting (IDW) and
      ordinary kriging (OK), to predict the distribution and abundance of hard corals,
      octocorals, macroalgae, sponges and zoantharians and identify hotspots of these
      habitat-forming organisms using data sampled at three different spatial scales
      (5, 10 and 20 m) in Madagascar reef, Gulf of Mexico. The deeper sandy
      environments of the leeward and windward regions of Madagascar reef were
      dominated by macroalgae and seconded by octocorals. However, the shallow rocky
      environments of the reef crest had the highest richness of habitat-forming groups
      of organisms; here, we registered high abundances of octocorals and macroalgae,
      with sponges, Millepora alcicornis and zoantharians dominating in some patches,
      creating high levels of habitat heterogeneity. IDW and OK generated similar maps
      of distribution for all the taxa; however, cross-validation tests showed that IDW
      outperformed OK in the prediction of their abundances. When the sampling distance
      was at 20 m, both interpolation techniques performed poorly, but as the sampling
      was done at shorter distances prediction accuracies increased, especially for
      IDW. OK had higher mean prediction errors and failed to correctly interpolate the
      highest abundance values measured in situ, except for macroalgae, whereas IDW had
      lower mean prediction errors and high correlations between predicted and measured
      values in all cases when sampling was every 5 m. The accurate spatial
      interpolations created using IDW allowed us to see the spatial variability of
      each taxa at a biological and spatial resolution that remote sensing would not
      have been able to produce. Our study sets the basis for further research projects
      and conservation management in Madagascar reef and encourages similar studies in
      the region and other parts of the world where remote sensing technologies are not
      suitable for use.

PMID- 29204322
TI  - Diagnosis value of aberrantly expressed microRNA profiles in lung squamous cell
      carcinoma: a study based on the Cancer Genome Atlas.
AB  - Background: Lung cancer is considered as one of the most frequent and deadly
      cancers with high mortality all around the world. It is critical to find new
      biomarkers for early diagnosis of lung cancer, especially lung squamous cell
      carcinoma (LUSC). The Cancer Genome Atlas (TCGA) is a database which provides
      both cancer and clinical information. This study is a comprehensive analysis of a
      novel diagnostic biomarker for LUSC, based on TCGA. Methods and Results: The
      present study investigated LUSC-specific key microRNAs (miRNAs) from large-scale
      samples in TCGA. According to exclusion criteria and inclusion criteria, the
      expression profiles of miRNAs with related clinical information of 332 LUSC
      patients were obtained. Most aberrantly expressed miRNAs were identified between
      tumor and normal samples. Forty-two LUSC-specific intersection miRNAs (fold
      change >2, p < 0.05) were obtained by an integrative computational method, among
      them six miRNAs were found to be aberrantly expressed concerning characteristics
      of patients (gender, lymphatic metastasis, patient outcome assessment) through
      Student t-test. Five miRNAs correlated with overall survival (log-rank p < 0.05)
      were obtained through the univariate Cox proportional hazards regression model
      and Mantel-Haenszel test. Then, five miRNAs were randomly selected to validate
      the expression in 47 LUSC patient tissues using quantitative real-time polymerase
      chain reaction. The results showed that the test findings were consistent with
      the TCGA findings. Also, the diagnostic value of the specific key miRNAs was
      determined by areas under receiver operating characteristic curves. Finally, 577
      interaction mRNAs as the targets of 42 LUSC-specific intersection miRNAs were
      selected for further bioinformatics analysis. Conclusion: This study indicates
      that this novel microRNA expression signature may be a useful biomarker of the
      diagnosis for LUSC patients, based on bioinformatics analysis.

PMID- 29204323
TI  - Ability to predict repetitions to momentary failure is not perfectly accurate,
      though improves with resistance training experience.
AB  - 'Repetitions in Reserve' (RIR) scales in resistance training (RT) are used to
      control effort but assume people accurately predict performance a priori (i.e.
      the number of possible repetitions to momentary failure (MF)). This study
      examined the ability of trainees with different experience levels to predict
      number of repetitions to MF. One hundred and forty-one participants underwent a
      full body RT session involving single sets to MF and were asked to predict the
      number of repetitions they could complete before reaching MF on each exercise.
      Participants underpredicted the number of repetitions they could perform to MF
      (Standard error of measurements [95% confidence intervals] for combined sample
      ranged between 2.64 [2.36-2.99] and 3.38 [3.02-3.83]). There was a tendency
      towards improved accuracy with greater experience. Ability to predict repetitions
      to MF is not perfectly accurate among most trainees though may improve with
      experience. Thus, RIR should be used cautiously in prescription of RT. Trainers
      and trainees should be aware of this as it may have implications for the
      attainment of training goals, particularly muscular hypertrophy.

PMID- 29204324
TI  - Examining publication bias-a simulation-based evaluation of statistical tests on
      publication bias.
AB  - Background: Publication bias is a form of scientific misconduct. It threatens the
      validity of research results and the credibility of science. Although several
      tests on publication bias exist, no in-depth evaluations are available that
      examine which test performs best for different research settings. Methods: Four
      tests on publication bias, Egger's test (FAT), p-uniform, the test of excess
      significance (TES), as well as the caliper test, were evaluated in a Monte Carlo
      simulation. Two different types of publication bias and its degree (0%, 50%,
      100%) were simulated. The type of publication bias was defined either as file
      drawer, meaning the repeated analysis of new datasets, or p-hacking, meaning the
      inclusion of covariates in order to obtain a significant result. In addition, the
      underlying effect (beta = 0, 0.5, 1, 1.5), effect heterogeneity, the number of
      observations in the simulated primary studies (N = 100, 500), and the number of
      observations for the publication bias tests (K = 100, 1,000) were varied.
      Results: All tests evaluated were able to identify publication bias both in the
      file-drawer and p-hacking condition. The false positive rates were, with the
      exception of the 15%- and 20%-caliper test, unbiased. The FAT had the largest
      statistical power in the file-drawer conditions, whereas under p-hacking the TES
      was, except under effect heterogeneity, slightly better. The CTs were, however,
      inferior to the other tests under effect homogeneity and had a decent statistical
      power only in conditions with 1,000 primary studies. Discussion: The FAT is
      recommended as a test for publication bias in standard meta-analyses with no or
      only small effect heterogeneity. If two-sided publication bias is suspected as
      well as under p-hacking the TES is the first alternative to the FAT. The 5%
      caliper test is recommended under conditions of effect heterogeneity and a large
      number of primary studies, which may be found if publication bias is examined in
      a discipline-wide setting when primary studies cover different research problems.

PMID- 29204325
TI  - Acute ischemic preconditioning does not influence high-intensity intermittent
      exercise performance.
AB  - This study evaluated the acute effect of ischemic preconditioning (IPC) on a high
      intensity intermittent exercise performance and physiological indicators in
      amateur soccer players. Thirteen players (21.5 +/- 2 yrs) attended three trials
      separated by 3-5 days in a counterbalanced randomized cross-over design: IPC (4 *
      5-min occlusion 220 mmHg/reperfusion 0 mmHg) in each thigh; SHAM (similar to the
      IPC protocol but "occlusion" at 20 mmHg) and control (seated during the same time
      of IPC). After 6-min of each trial (IPC, SHAM or control), the players performed
      the YoYo Intermittent Endurance Test level 2 (YoYoIE2). The distance covered in
      the YoYoIE2 (IPC 867 +/- 205 m; SHAM 873 +/- 212 m; control 921 +/- 206 m) was
      not different among trials (p = 0.10), furthermore, lactate concentration and
      rate of perceived exertion did not differ (P > 0.05) among protocols. There were
      also no significant differences in either mean heart rate (HR) or peak HR (p >
      0.05) for both IPC and SHAM compared to control. Therefore, we conclude that
      acute IPC does not influence high-intensity intermittent exercise performance in
      amateur soccer players and that rate of perceived exertion, heart rate and
      lactate do not differ between the intervention IPC, SHAM and control.

PMID- 29204326
TI  - A tyrannosauroid metatarsus from the Merchantville Formation of Delaware
      increases the diversity of non-tyrannosaurid tyrannosauroids on Appalachia.
AB  - During the Late Cretaceous, the continent of North America was divided into two
      sections: Laramidia in the west and Appalachia in the east. Although the
      sediments of Appalachia recorded only a sparse fossil record of dinosaurs, the
      dinosaur faunas of this landmass were different in composition from those of
      Laramidia. Represented by at least two taxa (Appalachiosaurus montgomeriensis and
      Dryptosaurus aquilunguis), partial and fragmentary skeletons, and isolated bones,
      the non-tyrannosaurid tyrannosauroids of the landmass have attracted some
      attention. Unfortunately, these eastern tyrants are poorly known compared to
      their western contemporaries. Here, one specimen, the partial metatarsus of a
      tyrannosauroid from the Campanian Merchantville Formation of Delaware, is
      described in detail. The specimen can be distinguished from A. montgomeriensis
      and D. aquilunguis by several morphological features. As such, the specimen
      represents a potentially previously unrecognized taxon of tyrannosauroid from
      Appalachia, increasing the diversity of the clade on the landmass. Phylogenetic
      analysis and the morphology of the bones suggest the Merchantville specimen is a
      tyrannosauroid of "intermediate" grade, thus supporting the notion that
      Appalachia was a refugium for relict dinosaur clades.

PMID- 29204327
TI  - Automated Assessment of Dynamic Knee Valgus and Risk of Knee Injury During the
      Single Leg Squat.
AB  - Many clinical assessment protocols of the lower limb rely on the evaluation of
      functional movement tests such as the single leg squat (SLS), which are often
      assessed visually. Visual assessment is subjective and depends on the experience
      of the clinician. In this paper, an inertial measurement unit (IMU)-based method
      for automated assessment of squat quality is proposed to provide clinicians with
      a quantitative measure of SLS performance. A set of three IMUs was used to
      estimate the joint angles, velocities, and accelerations of the squatting leg.
      Statistical time domain features were generated from these measurements. The most
      informative features were used for classifier training. A data set of SLS
      performed by healthy participants was collected and labeled by three expert
      clinical raters using two different labeling criteria: "observed amount of knee
      valgus" and "overall risk of injury". The results showed that both flexion at the
      hip and knee, as well as hip and ankle internal rotation are discriminative
      features, and that participants with "poor" squats bend the hip and knee less
      than those with better squat performance. Furthermore, improved classification
      performance is achieved for females by training separate classifiers stratified
      by gender. Classification results showed excellent accuracy, 95.7 % for
      classifying squat quality as "poor" or "good" and 94.6% for differentiating
      between high and no risk of injury.

PMID- 29204329
TI  - Rare Aggressive Calvarial Osteoblastoma with Dural Invasion.
AB  - We report a rare case of an aggressive osteoblastoma (OB) involving the calvaria
      and infiltrating the dura, a finding that was not previously reported in the
      literature. A 50-year-old man presented with a progressive mass in the left
      frontoparietal skull with headaches and a six-month history of sudden mass
      growth. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a
      large skull lesion with areas of hemorrhage, calcification, restricted diffusion,
      and enhancement.  A left temporoparietal craniotomy with a complete resection of
      the tumor with grossly clean margins was performed. Follow-up at 60 months showed
      a stable clinical picture and no sign of local recurrence of the lesion on MRI.

PMID- 29204330
TI  - A Bias in the Evaluation of Bias Comparing Randomized Trials with Nonexperimental
      Studies.
AB  - In a recent BMJ article, the authors conducted a meta-analysis to compare
      estimated treatment effects from randomized trials with those derived from
      observational studies based on routinely collected data (RCD). They calculated a
      pooled relative odds ratio (ROR) of 1.31 (95% confidence interval [CI]: 1.03
      1.65) and concluded that RCD studies systematically over-estimated protective
      effects. However, their meta-analysis inverted results for some clinical
      questions to force all estimates from RCD to be below 1. We evaluated the
      statistical properties of this pooled ROR, and found that the selective inversion
      rule employed in the original meta-analysis can positively bias the estimate of
      the ROR. We then repeated the random effects meta-analysis using a different
      inversion rule and found an estimated ROR of 0.98 (0.78-1.23), indicating the ROR
      is highly dependent on the direction of comparisons. As an alternative to the
      ROR, we calculated the observed proportion of clinical questions where the RCD
      and trial CIs overlap, as well as the expected proportion assuming no systematic
      difference between the studies. Out of 16 clinical questions, 50% CIs overlapped
      for 8 (50%; 25 to 75%) compared with an expected overlap of 60% assuming no
      systematic difference between RCD studies and trials. Thus, there was little
      evidence of a systematic difference in effect estimates between RCD and RCTs.
      Estimates of pooled RORs across distinct clinical questions are generally not
      interpretable and may be misleading.

PMID- 29204328
TI  - The Role of Affordable, Point-of-Care Technologies for Cancer Care in Low- and
      Middle-Income Countries: A Review and Commentary.
AB  - As the burden of non-communicable diseases such as cancer continues to rise in
      low- and middle-income countries (LMICs), it is essential to identify and invest
      in promising solutions for cancer control and treatment. Point-of-care
      technologies (POCTs) have played critical roles in curbing infectious disease
      epidemics in both high- and low-income settings, and their successes can serve as
      a model for transforming cancer care in LMICs, where access to traditional
      clinical resources is often limited. The versatility, cost-effectiveness, and
      simplicity of POCTs warrant attention for their potential to revolutionize cancer
      detection, diagnosis, and treatment. This paper reviews the landscape of
      affordable POCTs for cancer care in LMICs with a focus on imaging tools, in vitro
      diagnostics, and treatment technologies and aspires to encourage innovation and
      further investment in this space.

PMID- 29204331
TI  - Pharmacoepidemiology in the era of real-world evidence.

PMID- 29204332
TI  - Estimating Effects of Dynamic Treatment Strategies in Pharmacoepidemiologic
      Studies with Time-varying Confounding: A Primer.
AB  - Purpose of review: Pharmacoepidemiologists are often interested in estimating the
      effects of dynamic treatment strategies, where treatments are modified based on
      patients' evolving characteristics. For such problems, appropriate control of
      both baseline and time-varying confounders is critical. Conventional methods that
      control confounding by including time-varying treatments and confounders in an
      outcome regression model may not have a causal interpretation, even when all
      baseline and time-varying confounders are measured. This problem occurs when time
      varying confounders are, themselves, affected by past treatment. We review
      alternative analytic approaches that can produce valid inferences in the presence
      of such confounding. We focus on the parametric g-formula and inverse probability
      weighting of marginal structural models, two examples of Robins' g-methods.
      Recent findings: Unlike standard outcome regression methods, the parametric g
      formula and inverse probability weighting of marginal structural models can
      estimate the effects of dynamic treatment strategies and appropriately control
      for measured time-varying confounders affected by prior treatment. Few
      applications of g-methods exist in the pharmacoepidemiology literature, primarily
      due to the common use of administrative claims data, which typically lack
      detailed measurements of time-varying information, and the limited availability
      of or familiarity with tools to help perform the relatively complex analysis.
      These barriers may be overcome with the increasing availability of data sources
      containing more detailed time-varying information and more accessible learning
      tools and software. Summary: With appropriate data and study design, g-methods
      can improve our ability to make causal inferences on dynamic treatment strategies
      from observational data in pharmacoepidemiology.

PMID- 29204333
TI  - Development and application of two semi-automated tools for targeted medical
      product surveillance in a distributed data network.
AB  - Purpose of Review: An important component of the Food and Drug Administration's
      Sentinel Initiative is the active post-market risk identification and analysis
      (ARIA) system, which utilizes semi-automated, parameterized computer programs to
      implement propensity-score adjusted and self-controlled risk interval designs to
      conduct targeted surveillance of medical products in the Sentinel Distributed
      Database. In this manuscript, we review literature relevant to the development of
      these programs and describe their application within the Sentinel Initiative.
      Recent Findings: These quality-checked and publicly available tools have been
      successfully used to conduct rapid, replicable, and targeted safety analyses of
      several medical products. In addition to speed and reproducibility, use of semi
      automated tools allows investigators to focus on decisions regarding key
      methodological parameters. We also identified challenges associated with the use
      of these methods in distributed and prospective datasets like the Sentinel
      Distributed Database, namely uncertainty regarding the optimal approach to
      estimating propensity scores in dynamic data among data partners of heterogeneous
      size. Summary: Future research should focus on the methodological challenges
      raised by these applications as well as developing new modular programs for
      targeted surveillance of medical products.

PMID- 29204334
TI  - Norovirus Disease in Older Adults Living in Long-Term Care Facilities: Strategies
      for Management.
AB  - Purpose of Review: Noroviruses are the most common cause of gastroenteritis
      outbreaks in long-term care facility (LTCFs). This review summarizes the most up
      to-date knowledge on norovirus infection in LTCFs with the aim of identifying
      potential strategies for management. Recent Findings: LTCF residents are at
      greater risk of norovirus infection. Early identification of norovirus infection
      and prompt initiation of appropriate supportive therapy are required to reduce
      morbidity and mortality. Measures to prevent outbreaks and reduce the risk of
      norovirus infection in LTCFs include timely diagnosis and implementation of
      infection control interventions to limit virus transmission. Summary: Current
      guidelines for prevention and control are based on generic principles of
      infection control. Real-time reverse transcription-quantitative polymerase chain
      reaction assays have been the gold standard for the rapid and sensitive detection
      of noroviruses. With the recent breakthroughs of human norovirus in vitro
      culture, doors are now opened to evaluate the efficacy of environmental
      disinfectants and hand hygiene options. Additionally, development of licensed
      vaccines against noroviruses may provide another important tool for infection
      prevention among high-risk individuals.

PMID- 29204335
TI  - Temporal trends in lipid testing among children and adolescents: A population
      based study.
AB  - Unfavorable lipid levels during childhood are associated with subsequent
      development of atherosclerotic cardiovascular disease. The American Academy of
      Pediatrics and National Heart, Lung and Blood Institute in 2011 recommended
      universal lipid screening for children between ages 9-11 years and between ages
      17-21 years. The objective of the study was to determine temporal trends in lipid
      testing among children and young adults in a mid-western population. The
      Rochester Epidemiology Project database was used to identify lipid testing in
      ages 2-21 years (n = 51,176) in the Olmsted County population from January 1,
      2008 through December 31, 2014. Generalized estimating equations with Poisson
      distribution were used to test for temporal trends in lipid testing across the
      age groups. There was modest increase in lipid testing in children in the age
      groups, 9-11 years and 17-21 years (1.5% in 2008 to 2.2% in 2014, P < 0.001 and
      4.4% in 2008 to 4.6% in 2014, P = 0.02, respectively). There was a significant
      decrease in proportion of 17-21 year olds with elevated total cholesterol (16.2%
      in 2008 to 11.6% in 2014; P = 0.01) and non-high density lipoprotein cholesterol
      (22.6% in 2008 to 12.6% in 2014; P < 0.001). In this population-based study,
      rates of lipid testing increased minimally only in the last six years. Further
      longitudinal studies are warranted to improve guideline dissemination and address
      attitudes, practices and barriers to lipid testing in children and young adults.

PMID- 29204336
TI  - Sporotrichosis by Sporothrix schenckii senso stricto with itraconazole resistance
      and terbinafine sensitivity observed in vitro and in vivo: Case report.
AB  - We report a case of a patient with lymphocutaneous sporotrichosis in the right
      upper limb. The fungus was identified as Sporothrix schenckii senso stricto by
      calmodulin gene sequencing. The initial treatment was itraconazole (200 mg/day),
      but in vitro antifungal susceptibility demonstrated high resistant to this and
      another six antifungals, with exception to terbinafine. The lesions did not
      regress with itraconazole treatment. Thus, 500 mg/day of terbinafine was
      prescribed and clinical cure was obtained after four months.

PMID- 29204337
TI  - Effects on bone resorption markers of continuing pamidronate or switching to
      zoledronic acid in patients with high risk bone metastases from breast cancer.
AB  - Background: Switching patients who remain at high risk of skeletal related events
      (SREs) despite pamidronate to the more potent bisphosphonate zoledronate, may be
      an effective treatment strategy. As part of a previously reported clinic study in
      this setting, we evaluated whether biomarkers for bone resorption, such as Bone
      Specific Alkaline Phosphatase (BSAP), bone sialoprotein (BSP), and N-terminal
      telopeptide (NTX) correlated with subsequent SRE risk. Methods: Breast cancer
      patients who remained at high risk of SREs despite at least 3 months of q.3-4
      weekly pamidronate were randomized to either continue on pamidronate or to switch
      to zoledronate (4 mg) once every 4 weeks for 12-weeks. High risk bone metastases
      were defined by either: occurrence of a prior SRE, bone pain, radiologic
      progression of bone metastases and/or serum C-terminal telopeptide (CTx) levels >
      400 ng/L despite pamidronate use. Serum samples were collected at baseline and
      weeks 1, 4, 8 and 12 (CTx and BSAP) and baseline and week 12 (NTx and BSP), and
      all putative biomarkers were measured by ELISA. Follow up was extended to 2 years
      post trial entry for risk of subsequent SREs. The Kaplan-Meier method was used to
      estimate time-to-event outcomes. Generalized estimating equations (GEE) were used
      to evaluate if laboratory values over time or the change in laboratory values
      from baseline were associated with having a SRE within the time frame of this
      study. Results: From March 2012 to May 2014, 76 patients were screened, with 73
      eligible for enrolment. All 73 patients were available for biochemical analysis,
      with 35 patients receiving pamidronate and 38 patients receiving zoledronate. The
      GEE analysis found that no laboratory value was associated with having a
      subsequent SRE. Interaction between visit and laboratory values was also
      investigated, but no interaction effect was statistically significant. Only
      increased number of lines of prior hormonal treatment was associated with
      subsequent SRE risk. Conclusion: Our analysis failed to find any association
      between serum BSAP, BSP, CTx or NTx levels and subsequent SRE risk in this cohort
      of patients. This lack of correlation between serum biomarkers and clinical
      outcomes could be due to influences of prior bisphosphonate treatment or presence
      of extra-osseous metastases in a significant proportion of enrolled patients. As
      such, caution should be used in biomarker interpretation and use to direct
      decision making regarding SRE risk for high risk patients in this setting.

PMID- 29204338
TI  - Giant left atrium encountered during right-sided thoracentesis.
AB  - Giant left atrium is an uncommon pathology to encounter during bedside chest
      ultrasound, but is an important structure to be aware of when considering
      thoracentesis. This cardiac structure could easily be mistaken for loculated
      pleural fluid. This case also supports growing evidence that expert users can
      safely perform thoracentesis without completely reversing therapeutic
      anticoagulation.

PMID- 29204339
TI  - Chest pain in a young immunocompetent male: A rare case scenario.
AB  - Musculoskeletal tuberculosis is the commonest form of extrapulmonary tuberculosis
      however Rib lesion is uncommon and occurs in zero to five percent of bone and
      joint tuberculosis. In our case report both chest X ray and CT were useful in
      demonstrating the skeletal lesion and also in the assessment of response to
      treatment, as follow up chest X ray and CT scan at 4 months and after 12 months
      of anti tubercular drugs showed remarkable new bone formation and clearing of
      pleura parenchymal lesions.

PMID- 29204340
TI  - Evaluation of coexistence of cancer and active tuberculosis; 16 case series.
AB  - Introduction: Tuberculosis is an important risk factor for cancer. Pulmonary TB
      and lung cancer(LC) may mimic each other especially in the aspect of the clinical
      and radiological features. The aim of the study was to evaluate the features and
      risk factors of cases with coexistence cancer and active TB. Methodology: We
      retrospectively reviewed the medical records of patients with coexisting TB and
      cancer a period from 2009 to 2014. We evaluated demographic data, the ways
      diagnosis of TB cases, the location of TB and cancer, TB treatment results of the
      cases. Results: We recorded 374 TB cases in our dyspensary at this study period.
      In 16 (4%) of these cases, a coexistence of cancer and TB was detected. The
      male/female ratio was 12/4. The mean age was 62,12 +/- 15,13 years. There were
      TST results except three cases. There were ten pulmonary TB and six extra
      pulmonary TB (four peripheral lymphadenopathy TB, one abdominal TB
      lymphadenopathy and one salivary gland TB). Cancer types were as follows; eight
      lung cancer, two breast cancer, one base of tongue, one endometrium cancer, one
      hypopharyngeal cancer, one stomach cancer, one bladder cancer and one maxillary
      cancer. Diagnosis of all cases was confirmed by bacteriologic and/or
      histopathological examination. Squamous cell carcinoma was the most common type
      of cancers. This rate was 9/16. All TB cases were new. There were risk factors
      out of two case in the cases. Five cases were died during TB treatment. Others
      completed TB treatment without any complication. Conclusions: In our study, the
      coexistence of LC and pulmonary TB was more common. The local immunity is
      deteriorated in cancer cases. If there is pulmonary infiltrates in lung or
      peripheral lymphadenopathy, we must search tuberculosis too out of metastatic
      lesion and other infectious diseases. We should not make delay in the diagnosis
      of active TB in cancer cases.

PMID- 29204341
TI  - Case report: Exome sequencing identifies T-ALL with myeloid features as a IKZF1
      struck early precursor T-cell malignancy.

PMID- 29204342
TI  - Sex differences in white matter alterations following repetitive subconcussive
      head impacts in collegiate ice hockey players.
AB  - Objective: Repetitive subconcussive head impacts (RSHI) may lead to structural,
      functional, and metabolic alterations of the brain. While differences between
      males and females have already been suggested following a concussion, whether
      there are sex differences following exposure to RSHI remains unknown. The aim of
      this study was to identify and to characterize sex differences following exposure
      to RSHI. Methods: Twenty-five collegiate ice hockey players (14 males and 11
      females, 20.6 +/- 2.0 years), all part of the Hockey Concussion Education Project
      (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and
      after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and
      did not experience a concussion during the season. Whole-brain tract-based
      spatial statistics (TBSS) were used to compare pre- and postseason imaging in
      both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive
      performance were assessed by the Immediate Post-Concussion Assessment and
      Cognitive Test (ImPACT). Results: Significant differences between the sexes were
      primarily located within the superior longitudinal fasciculus (SLF), the internal
      capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In
      significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre-
      vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD
      (0.00005) were observed in females whereas males showed no significant changes.
      There was no significant correlation between the change in diffusion scalar
      measures over the course of the season and neurocognitive performance as
      evidenced from postseason ImPACT scores. Conclusions: The results of this study
      suggest sex differences in structural alterations following exposure to RSHI.
      Future studies need to investigate further the underlying mechanisms and
      association with exposure and clinical outcomes.

PMID- 29204343
TI  - Episodic memory after trauma exposure: Medial temporal lobe function is
      positively related to re-experiencing and inversely related to negative affect
      symptoms.
AB  - Hippocampal structure is particularly sensitive to trauma and other stressors.
      However, previous findings linking hippocampal function with trauma-related
      psychopathology have been mixed. Heterogeneity in psychological responses to
      trauma has not been considered with respect to hippocampal function and may
      contribute to mixed findings. To address these issues, we examined associations
      between data-driven symptom dimensions and episodic memory formation, a key
      function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were
      defined using principal components analysis (PCA) in 3881 trauma-exposed African
      American women recruited from primary care waiting rooms of a large urban
      hospital. Hippocampal and amygdala function were subsequently investigated in an
      fMRI study of episodic memory formation in a subset of 54 women. Participants
      viewed scenes with neutral, negative, and positive content during fMRI, and
      completed a delayed cued recall task. PCA analysis produced five symptom
      dimensions interpreted as reflecting negative affect, somatic symptoms, re
      experiencing, hyper-arousal, and numbing. Re-experiencing was the only symptom
      type associated with hippocampal function, predicting increased memory encoding
      related activation in the hippocampus as well as the amygdala. In contrast, the
      negative affect component predicted lower amygdala activation for subsequently
      recalled scenes, and lower functional coupling with other important memory
      related regions including the precuneus, inferior frontal gyrus, and occipital
      cortex. Symptom dimensions were not related to hippocampal volume. The fMRI
      findings for re-experiencing versus negative affect parallel differences in
      behavioral memory phenomena in PTSD versus MDD, and highlight a need for more
      complex models of trauma-related pathology.

PMID- 29204345
TI  - Localization of ictal pouting in frontal lobe epilepsy: A case report.

PMID- 29204344
TI  - MR brain volumetric measurements are predictive of neurobehavioral impairment in
      the HIV-1 transgenic rat.
AB  - Introduction: HIV infection is known to be associated with brain volume loss,
      even in optimally treated patients. In this study, we assessed whether dynamic
      brain volume changes over time are predictive of neurobehavorial performance in
      the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients.
      Materials and methods: Cross-sectional brain MRI imaging was first performed
      comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI
      and neurobehavioral testing of another group of Tg and WT rats was then performed
      from 5 to 23 weeks of age. Whole brain and subregional image segmentation was
      used to assess the rate of brain growth over time. We used repeated-measures
      mixed models to assess differences in brain volumes and to establish how
      predictive the volume differences are of specific neurobehavioral deficits.
      Results: Cross-sectional imaging showed smaller whole brain volumes in Tg
      compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain
      volumes were smaller than age-matched WT rats at all time points, starting as
      early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks
      of age was greater than that of the whole brain. Striatal volume in combination
      with genotype was the most predictive of rota-rod scores and in combination with
      genotype and age was the most predictive of total exploratory activity scores in
      the Tg rats. Conclusion: The disproportionately delayed striatal growth compared
      to whole brain between 5 and 9 weeks of age and the role of striatal volume in
      predicting neurobehavioral deficits suggest an important role of the dopaminergic
      system in HIV associated neuropathology. This might explain problems with motor
      coordination and executive decisions in this animal model. Smaller brain and
      subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of
      age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy
      testing in this model should thus target this early stage of development, before
      brain damage becomes irreversible.

PMID- 29204346
TI  - Drug-induced hypersensitivity syndrome caused by valproic acid as a monotherapy
      for epilepsy: First case report in Asian population.
AB  - Valproic acid (VPA) is a broad-spectrum antiseizure drug used for a variety of
      clinical conditions, such as epilepsy and mood disorders. Drug-induced
      hypersensitivity syndrome (DRESS) accompanied by hyponatremia, thrombocytopenia,
      hypoalbuminemia and elevated aminotransferase has never been reported as an
      adverse effect of VPA monotherapy during titration for epilepsy in Asian
      population. Hereby, we present the case of a 73-year-old Chinese male who
      suffered from DRESS and other complications two weeks after initiating VPA
      treatment for epilepsy. Understanding the risk associated with VPA-induced DRESS,
      and taking effective measures to avoid the severe side effects are necessary.

PMID- 29204347
TI  - Impairment of consciousness induced by bilateral electrical stimulation of the
      frontal convexity.
AB  - We report a case of impairment of consciousness (IOC) induced by electrical
      cortical stimulation (ECS) of homologous regions within the lateral frontal
      convexities in a patient with medically intractable epilepsy. The patient had
      mixed features of idiopathic generalized and focal epilepsy. On intracranial EEG
      recording, interictal and ictal discharges showed a high degree of synchrony
      across widespread bilateral fronto-parietal areas. We identified regions in the
      lateral frontal lobes that reliably and produced loss of consciousness by ECS.
      This was accompanied by evoked EEG activity of admixed frequencies over the
      fronto-parietal, mesial frontal and temporal regions during stimulation and was
      not associated with after-discharges. Symptoms were immediately reversible upon
      cessation of stimulation. This finding suggests that focal cortical stimulation
      can disrupt widespread networks that underlie consciousness. Individuals with
      high degrees of speculated thalamo-frontal cortical connectivity might be more
      susceptible to this effect, and the findings highlight the importance of
      standardizing the testing of level of consciousness during mapping sessions.
      Although consciousness is commonly impaired in epileptic seizures, limited
      literature is available on loss of consciousness induced by electrical cortical
      stimulation (ECS) in humans undergoing intracranial EEG evaluations for
      localization of epileptic focus. One theory advocates the presence of
      consciousness 'switch' in subcortical structures. While this model is novel and
      simplistic, it has its inherent limitations. In this case study, we propose an
      alternative approach on the entity and discuss the complex circuits underlying it
      and correlate that with the electrophysiological findings and the pathophysiology
      of the phenotype of the disease and discuss potential causes for rarity of
      reports on the subject.

PMID- 29204348
TI  - Non ictal onset zone: A window to ictal dynamics.
AB  - The focal and network concepts of epilepsy present different aspects of
      electroclinical phenomenon of seizures. Here, we present a 23-year-old man
      undergoing surgical evaluation with left fronto-temporal electrocorticography
      (ECoG) and microelectrode-array (MEA) in the middle temporal gyrus (MTG). We
      compare action-potential (AP) and local field potentials (LFP) recorded from MEA
      with ECoG. Seizure onset in the mesial-temporal lobe was characterized by changes
      in the pattern of AP-firing without clear changes in LFP or ECoG in MTG. This
      suggests simultaneous analysis of neuronal activity in differing spatial scales
      and frequency ranges provide complementary insights into how focal and network
      neurophysiological activity contribute to ictal activity.

PMID- 29204350
TI  - Heart rate variability in concussed athletes: A case report using the smartphone
      electrocardiogram.

PMID- 29204351
TI  - Implantation of a dual-chamber permanent pacemaker in a pregnant patient guided
      by intracardiac echocardiography and electroanatomic mapping.

PMID- 29204349
TI  - Annotation of nerve cord transcriptome in earthworm Eisenia fetida.
AB  - In annelid worms, the nerve cord serves as a crucial organ to control the sensory
      and behavioral physiology. The inadequate genome resource of earthworms has
      prioritized the comprehensive analysis of their transcriptome dataset to monitor
      the genes express in the nerve cord and predict their role in the
      neurotransmission and sensory perception of the species. The present study
      focuses on identifying the potential transcripts and predicting their functional
      features by annotating the transcriptome dataset of nerve cord tissues prepared
      by Gong et al., 2010 from the earthworm Eisenia fetida. Totally 9762 transcripts
      were successfully annotated against the NCBI nr database using the BLASTX
      algorithm and among them 7680 transcripts were assigned to a total of 44,354 GO
      terms. The conserve domain analysis indicated the over representation of P-loop
      NTPase domain and calcium binding EF-hand domain. The COG functional annotation
      classified 5860 transcript sequences into 25 functional categories. Further, 4502
      contig sequences were found to map with 124 KEGG pathways. The annotated contig
      dataset exhibited 22 crucial neuropeptides having considerable matches to the
      marine annelid Platynereis dumerilii, suggesting their possible role in
      neurotransmission and neuromodulation. In addition, 108 human stem cell marker
      homologs were identified including the crucial epigenetic regulators,
      transcriptional repressors and cell cycle regulators, which may contribute to the
      neuronal and segmental regeneration. The complete functional annotation of this
      nerve cord transcriptome can be further utilized to interpret genetic and
      molecular mechanisms associated with neuronal development, nervous system
      regeneration and nerve cord function.

PMID- 29204352
TI  - Fractionated electrograms with ST-segment elevation recorded from the human right
      ventricular outflow tract.

PMID- 29204353
TI  - Sphingomonas paucimobilis presenting as acute phlebitis: A case report.
AB  - Sphingomonas paucimobilis is a strictly aerobic, non-spore-forming Gram-negative
      bacillus, ubiquitous bacterium, thought to be an opportunistic pathogen and is
      rarely reported in clinical settings. Here in, is the first case report of Acute
      Sphingomonas phlebitis secondary to intravenous (IV) drug use. We present the
      case of a 39-year-old male who initially presented with pain in his right upper
      extremity, fevers and chills of three week duration. He admitted to regularly
      injecting heroin in his distal right upper extremity with visible erythema,
      tenderness and streaking along the path of vein along the injection site.
      Radiographic studies including X-ray of the right arm, ultrasound and a
      subsequent MRI of the right arm were not significant for any osteomyelitis, deep
      venous thrombus, abscess, cellulitis, osteomyelitis, or pyomyositis. Blood
      culture grew Sphingomonas paucimobilis. Patient was initially started on
      vancomycin and piperacillin/tazobactam and subsequently switched to levofloxacin
      to complete a 14 day course. Patient admitted to using toilet water to mix his
      heroin which we suspect may have been the source of his bacteremia. Since it was
      first reported in 1979, a wide variety of community-acquired and hospital
      acquired infections have been attributed to this Sphingomonas. It is ubiquitous
      to natural environment. We believe that due to its widespread habitat and ability
      to survive in stress conditions it could be a potential future threat in the era
      of increasing antimicrobial resistance globally. More research needs to be done
      on early identification, pathogenesis, treatment and eradication of the organism.

PMID- 29204354
TI  - Unusual carbapenem resistant but ceftriaxone and cefepime susceptible Klebsiella
      oxytoca isolated from a blood culture: Case report and whole-genome sequencing
      investigation.
AB  - A carbapenem resistant but ceftriaxone and cefepime susceptible Klebsiella
      oxytoca was isolated from the blood of a patient with polymicrobial bacteremia
      after 2 weeks of ertapenem treatment. Whole-genome sequencing identified no
      carbapenemase gene nor plasmid, but only blaOXY-2-8 gene with a mutation in the
      promoter that's been reported to increase its expression. Two other specific
      carbapenem resistance mechanisms including mutated porin genes and the AcrAB-TolC
      efflux system genes were also identified. Clinicians need to be aware of such
      unusual antibiogram and should not assume carbapenems are always broader spectrum
      antibiotics than expanded-spectrum cephalosporins.

PMID- 29204355
TI  - Cardiac Transplantation in Dermatomyositis: A case report and literature review.
AB  - Background and objectives: Cardiac involvement has been well recognized in
      patients with dermatomyositis (DM) and polymyositis (PM) with a variable
      frequency between 9 and 72%. However, clinically significant heart involvement in
      DM/PM is relatively infrequent and there have been rare reports of cardiac
      transplantation in DM. Our aims were to describe a case of severe cardiac
      involvement in DM requiring heart transplantation and review the literature of
      cardiac disease in DM and PM. Methods: A patient with dermatomyositis who was
      referred to our institution with severe heart failure is described. Pathology of
      the patient's skeletal and cardiac muscle is reviewed. A MEDLINE database search
      of reports of cardiac involvement in DM and PM was also conducted. Results: A 36
      year-old man with DM presented with severe heart failure to our institution for
      evaluation of heart transplantation. After a three month hospitalization he
      underwent successful cardiac transplantation. Pathological examination of his
      explant heart revealed a pattern of inflammation and damage similar to DM in
      skeletal muscle. The patient is currently doing well, 20 months post-transplant,
      and is maintained on tacrolimus, cellcept, rituximab, and low dose prednisone. To
      our knowledge, this is the first case report of heart transplantation in
      dermatomyositis in which the muscle pathology is similar in both heart and
      skeletal muscle. Conclusions: Severe cardiac involvement requiring
      transplantation is rare in dermatomyositis but does occur and appears to be
      related to a similar inflammatory process as noted in the skeletal muscle.

PMID- 29204356
TI  - Ureteral Nephrogenic Adenoma in Chronic Recreational Ketamine Abuse.

PMID- 29204357
TI  - An infected thoracoabdominal aortic aneurysm mimicking the symptoms of urinary
      tract infection: A case report.

PMID- 29204358
TI  - Crohn's disease and multilocular cystic renal neoplasm of low malignant
      potential: An unusual association.

PMID- 29204359
TI  - Refractory urinary tract infection complicated rectus sheath abscess: A case
      report.

PMID- 29204360
TI  - A self-inflicted male urethral/vesical foreign body (olive seed) causing complete
      urinary retention.
AB  - Foreign body in the urethra is a relatively rare occurrence. A variety of foreign
      bodies, majority of which were mostly self-inflicted for psychiatric disorder,
      senility, intoxication, and autoerotic stimulation, have been reported in the
      literature. We report a case of self-inserted foreign body (olive seed) in the
      urethra.

PMID- 29204361
TI  - Double mucosal flap for the reconstruction of transverse vaginal septum - A novel
      surgical approach using the vaginal septal tissue.

PMID- 29204362
TI  - Incarcerated prolapsed ureterocele after midurethral sling in women.
AB  - Stress urinary incontinence (SUI) is a common problem in women. Successful
      treatment is now mid urethral sling but it would be a cause of urethral
      obstruction. In this case report, a 50 years old woman presented with a huge
      introitus mass after 3 months of midurethral sling. The mass protruded from the
      urethra and could not be reduced. Emergency MRI of pelvis was demonstrated
      prolapsed ureterocele, single system of right ureter. Preoperative planning was
      cystoscopy and mass excision. The patient was preoperatively counseled that right
      ureteric reimplantation may be required. Finally, the mass could be excised
      externally without reimplantation.

PMID- 29204363
TI  - Suspicious findings on micro-ultrasound imaging and early detection of prostate
      cancer.
AB  - The ExactVuTM Micro-Ultrasound system is a new high resolution imaging system for
      visualizing the prostate and has been FDA, CE, and Health Canada approved for
      visualization and biopsy of the prostate. The PRI-MUSTM (Prostate Risk
      Identification for Micro-Ultrasound) protocol has previously been demonstrated to
      correlate with risk of prostate cancer and severity of cancer. Here we present a
      case where a healthy 50 year old subject with no known risk factors volunteered
      to test the ExactVu system and was found to harbour multiple PRI-MUS 3-5 lesions.
      This prompted PSA testing, biopsy and eventual diagnosis of significant prostate
      cancer.

PMID- 29204364
TI  - Extramedullary plasmacytoma of the testis: A case report.

PMID- 29204366
TI  - Assessment of diabetic polyneuropathy in Zanzibar: Comparison between traditional
      methods and an automated point-of-care nerve conduction device.
AB  - Aim: Scant information is available about the prevalence of diabetic
      polyneuropathy, as well as the applicability of screening tools in sub-Saharan
      Africa. We aimed to investigate these issues in Zanzibar (Tanzania). Methods: One
      hundred consecutive diabetes patients were included from the diabetes clinic at
      Mnazi Mmoja Hospital. Clinical characteristics were recorded. Further, we
      investigated: a) self-reported numbness of the lower limbs, b) ten-point
      monofilament test, c) the Sibbald 60-s Tool and d) nerve conduction studies (NCS,
      using an automated handheld point-of-care device, the NC-stat DPNCheck). Results:
      Mean age was 54 years, 90% had type 2 diabetes, and with 9 year average disease
      duration. Mean HbA1c was 8.5% (69 mmol/mol), blood pressure 155/88 mmHg. Sixty
      two% reported numbness, 61% had positive monofilament and 79% positive Sibbald
      tool. NCS defined neuropathy in 45% of the patients. Only the monofilament showed
      appreciable concordance with the NCS, Cohen's kappa 0.43. Conclusions: The
      patient population was characterised by poor glycaemic control and hypertension.
      In line with this, neuropathy was rampant. The monofilament test tended to define
      more cases of probable neuropathy than the NCS, however specificity was rather
      low. Plantar skin thickening may have led to false positives in this population.
      Overall concordance was, however, appreciable, and could support continued use of
      monofilament as a neuropathy screening tool. The NC-stat DPNCheck could be useful
      in cases of diagnostic uncertainty or for research purposes in a low resource
      setting.

PMID- 29204365
TI  - The AGE-RAGE axis in an Arab population: The United Arab Emirates Healthy Futures
      (UAEHFS) pilot study.
AB  - Aims: The transformation of the United Arab Emirates (UAE) from a semi-nomadic to
      a high income society has been accompanied by increasing rates of obesity and
      Type 2 diabetes mellitus. We examined if the AGE-RAGE (receptor for advanced
      glycation endproducts) axis is associated with obesity and diabetes mellitus in
      the pilot phase of the UAE Healthy Futures Study (UAEHFS). Methods: 517 Emirati
      subjects were enrolled and plasma/serum levels of AGE, carboxy methyl lysine
      (CML)-AGE, soluble (s)RAGE and endogenous secretory (es)RAGE were measured along
      with weight, height, waist and hip circumference (WC/HC), blood pressure, HbA1c,
      Vitamin D levels and routine chemistries. The relationship between the AGE-RAGE
      axis and obesity and diabetes mellitus was tested using proportional odds models
      and linear regression. Results: After covariate adjustment, AGE levels were
      significantly associated with diabetes status. Levels of sRAGE and esRAGE were
      associated with BMI and levels of sRAGE were associated with WC/HC. Conclusions:
      The AGE-RAGE axis is associated with diabetes status and obesity in this Arab
      population. Prospective serial analysis of this axis may identify predictive
      biomarkers of obesity and cardiometabolic dysfunction in the UAEHFS.

PMID- 29204367
TI  - Protein and fat meal content increase insulin requirement in children with type 1
      diabetes - Role of duration of diabetes.
AB  - Background and objective: Hyperglycaemia remains a challenge in type 1 diabetes
      since current regimes used to determine meal insulin requirements prove to be
      ineffective. This is particularly problematic for meals containing high amounts
      of protein and fat. We aimed to determine the post-prandial glycaemic response
      and total insulin need for mixed meals, using sensor-augmented insulin pumps in
      children with type 1 diabetes. Methods: Twenty-two children with type 1 diabetes,
      aged 4-17 years on insulin pump therapy completed this home-based, cross-over,
      randomised controlled trial. Two meals with identical carbohydrate content - one
      with low fat and protein (LFLP) and one with high fat and protein (HFHP) contents
      - were consumed using normal insulin boluses. Blood glucose monitoring was done
      for 10 h post-meal, with correction bolus insulin given two-hourly if required.
      Results: The HFHP meal required significantly more total insulin (3.48 vs. 2.7
      units) as a result of increased post-meal correction insulin requirement (1.2 vs.
      0.15 units) spread over a longer duration (6 vs. 3 h). The HFHP meals
      significantly increased the time spent above target glucose level. Duration of
      diabetes and total daily insulin use significantly influenced the post-prandial
      blood glucose response to the two meals. Conclusion: When consuming carbohydrate
      based mixed meals, children with type 1 diabetes on insulin pump therapy,
      required significantly more insulin over a longer period of time than the insulin
      requirement calculated using current regimes. This additional amount required is
      influenced by the duration of diabetes and total daily insulin use.

PMID- 29204369
TI  - Effect of a vitamin and mineral supplementation on glycemic status: Results from
      a community-based program.
AB  - Aims: Diet is a major risk factor for type 2 diabetes mellitus. As cofactors
      necessary for enzyme function of all metabolic pathways, vitamins and minerals
      have the potential to improve glucose metabolism. We investigated the effects of
      a nutrient intervention program on glycemic status. Methods: We used a form of
      natural experiment to compare Pure North program participants (n = 1018) that
      received vitamin D alone (Vital 1) or vitamin D in combination with other
      nutrients (Vital 2) during two different time periods. Changes in 25
      hydroxyvitamin D [25(OH)D], high-sensitivity C reactive protein (hs-CRP),
      glycated hemoglobin (HbA1c) and glycemic status were characterized over one and
      two years. Results: Serum 25(OH)D concentrations increased significantly in both
      Vital 1 (to 111  +/-  49 nmol/L) and Vital 2 (to 119  +/-  52 nmol/L) over one
      year. HbA1c and hs-CRP were significantly reduced over time in Vital 2. Higher
      25(OH)D levels after one year were associated with larger decreases in HbA1c and
      hs-CRP in Vital 2. At one year, 8% of Vital 2 and 16% of Vital 1 participants
      progressed from normoglycemia to prediabetes/diabetes, whereas 44% of Vital 2 and
      8% of Vital prediabetes/diabetes subjects regressed to normoglycemia.
      Conclusions: Vitamin D combined with other nutrients was associated with a
      reduced risk of progression to diabetes and with an increased rate of reversion
      to normoglycemia in high risk participants. The results suggest that nutrient
      supplementation regimes may provide a safe, economical and effective means for
      lowering diabetes risk. Further examination of this potential via randomized
      controlled trials is warranted.

PMID- 29204368
TI  - Beneficial effects of oral pure caffeine on oxidative stress.
AB  - Ingestion of coffee (which is a mixture of over 1000 hydrosoluble substances) is
      known to protect from type-2 diabetes mellitus and its complications, and other
      chronic disorders associated with increased oxidative damage in blood and
      tissues. This protection is generally attributed to polyphenols and melanoidins.
      Very few studies were conducted on the amelioration of classic blood markers of
      oxidative stress induced after a few days of caffeine administration, but results
      vary. To assess whether caffeine per se could account for antioxidant properties
      of coffee in the short-term, we tested the ability of pure caffeine ingestion (5
      mg/kg body weight/day in two daily doses for seven consecutive days) to improve
      plasma levels of six biochemical indices in healthy male volunteers (n = 15).
      These indices were total antioxidant capacity (TAC), glutathione (GSH), oxidized
      glutathione (GSSG), GSH to GSSG ratio, lipid hydroperoxides (LOOH) and
      malondialdehyde (MDA). We found that all indices changed significantly (P < .05
      or < .01) in a favourable manner, ranging from -41% for GSSG to -70% for LHP
      levels, and +106% for GSH levels to +249% for the GSG/GSSG ratio. Changes of any
      given index were uniform across subjects, with no outliers. We conclude that
      caffeine has unequivocal, consistent antioxidant properties.

PMID- 29204370
TI  - Association of vitamin D with cathelicidin and vitamin D binding protein in
      pediatric sepsis.

PMID- 29204371
TI  - The prolactin receptor: Diverse and emerging roles in pathophysiology.
AB  - Investigations over two decades have revised understanding of the prolactin
      hormone. Long thought to be merely a lactogenic hormone, its list of functions
      has been extended to include: reproduction, islet differentiation, adipocyte
      control and immune modulation. Prolactin functions by binding cell-surface
      expressed prolactin receptor, initiating signaling cascades, primarily utilizing
      Janus kinase-signal transducer and activator of transcription (JAK-STAT). Pathway
      disruption has been implicated in tumorigenesis, reproductive abnormalities, and
      diabetes. Prolactin can also be secreted from extrapituitary sources adding
      complexity to understanding of its physiological functions. This review aims to
      describe how prolactin exerts its pathophysiological roles by endocrine and
      autocrine means.

PMID- 29204372
TI  - The impact of a low glycemic index (GI) breakfast and snack on daily blood
      glucose profiles and food intake in young Chinese adult males.
AB  - Objective: Low glycemic index (GI) foods have been suggested to minimize large
      fluctuations in blood glucose levels and reduce food intake. However, the
      majority of studies have been conducted on Caucasian populations with limited
      data on Asians. The objective of this study was to investigate how the provision
      of a low GI breakfast and afternoon snack affected daily blood glucose profiles
      and food intake. Materials and methods: In a randomized, controlled crossover non
      blind design, 11 healthy Chinese male adults (body mass index 22.4 +/- 1.3 kg m
      2) attended two sessions where they consumed either a high or low GI breakfast
      and afternoon snack, and a standardized buffet lunch. Daily changes in glycemic
      response (GR) were measured using the Medtronic MiniMed (Northridge, CA) iProTM2
      continuous glucose monitoring system (CGMS). The GR was further calculated to
      obtain the incremental area under the curve (IAUC). Glycemic variability was
      calculated as mean amplitude of glycemic excursion (MAGE) and energy intake
      (kcal) was measured quantitatively at the buffet lunch. Results: Compared to the
      high GI intervention, the low GI intervention significantly reduced the GR
      following breakfast (p = 0.02), lunch (p = 0.02) and dinner (p = 0.05). The low
      GI treatment showed a reduction in daily AUC (p = 0.03). There was a significant
      reduction in IAUC after a low GI breakfast compared to the high GI breakfast (p =
      0.03). The low GI breakfast resulted in a significantly lower food intake at
      lunch and a resulting decreased energy intake of 285 kcal (p = 0.02). The MAGE
      was significantly lower during the entire low GI treatment (p = 0.03).
      Conclusions: Consumption of a low GI breakfast and afternoon snack was capable of
      attenuating 24-h blood glucose profiles, minimize glycemic excursions and reduce
      food intake in healthy Asian males. This simple dietary intervention may be an
      acceptable approach in improving overall glycemia and energy balance in Asians.
      Clinical trial registration number: NCT02340507.

PMID- 29204373
TI  - Patients with type 1 diabetes in Sweden experience more fatigue than the general
      population.
AB  - Aims: Type 2 diabetes has been linked to fatigue, but results on type 1 diabetes
      are ambiguous. Our aim was to determine if type 1 diabetes is associated with
      fatigue and whether the fatigue is due to complications or to the disease itself.
      Methods: The Multidimensional Fatigue Inventory (MFI-20), was submitted to all
      435 adult patients with type 1 diabetes in the National Diabetes Register at the
      Sunderby Hospital clinic and to a control group of 2500 persons. The
      participation rate was 62% in both groups. Results: Type 1 diabetes was
      associated with greater fatigue, with a 1.4-point difference (0.9-1.9, 95% CI) in
      general fatigue on a scale of 4-20. Type 1 diabetes was an independent predictor
      of fatigue, as were cardiovascular and cerebrovascular disease. Women with long
      diabetes duration but without complications experienced more fatigue than women
      in the general population (difference in general fatigue = 2.5, p = 0.021),
      whereas men showed no significant difference. Conclusions: Type 1 diabetes is
      associated with greater fatigue, partly ascribed to vascular disease. Type 1
      diabetes of long duration might be associated with fatigue regardless of
      classical complications, but further research is needed to confirm results.

PMID- 29204374
TI  - Relationship between high normal TSH levels and metabolic syndrome components in
      type 2 diabetic subjects with euthyroidism.
AB  - Objective: Thyroid hormones as modulators of adaptive thermogenesis can
      potentially contribute to development of obesity. The purpose of our study is to
      observe a relationship between TSH and BMI, blood lipids, BP and HbA1c in type 2
      diabetic subjects with euthyroidism. Methods: A total of 120 subjects with type 2
      diabetes were recruited for this study from November 2012 to June 2014. Subjects
      were included in the study with TSH values between 0.4 and 4.5 mU/l, who did not
      take any thyroid medication and had a similar iodine diet. Subjects were weighed
      and anthropometric indices, lipid parameters, fasting plasma glucose, HbA1c,
      eGFR, blood pressure (BP) were documented. TSH was measured by an
      electrochemiluminescence immunoassay. Statistical analysis was performed by using
      SPSS 18(P value <0.05 was considered significant). Results: The mean age of the
      participants was 60.6 +/- 11.6 years with a BMI of 25.3 +/- 3.1 kg/m2. Serum TSH
      levels were significantly and positively associated with BMI, systolic and
      diastolic BP, serum triglyceride and HbA1c levels, whereas negatively with eGFR.
      Subjects with a TSH in a higher normal range (2.5-4.5 mU/I, n = 58) had a
      significantly higher BMI (26.7 +/- 3 vs. 24.1 +/- 2.7) and this relation remained
      significant adjusted for age and sex (P < 0.001). When TSH was in low normal
      range, the number of patients with glycemic goal (HbA1c > 7%) decreased from
      27.5% to 12.5% (P = 0.02, adjusted for age and sex). Conclusion: In type 2
      diabetic subjects with biochemical euthyroidism we found significant association
      between high normal TSH levels and components of metabolic syndrome. High normal
      TSH levels were associated with more number of subjects with glycemic goal (HbA1c
      >7%).

PMID- 29204375
TI  - Modified Langendorff technique for mouse heart cannulation: Improved heart
      quality and decreased risk of ischemia.
AB  - Oscar Langendorff introduced the first method for isolating a heart with
      contractile activity in 1895. Since then, the Langendorff method has remained a
      powerful technique in cardiac research and has led to major advances in medicine.
      The primary goal of the Langendorff method is to provide an isolated heart with
      oxygen and metabolites via a cannula inserted into the aorta. The Langendorff
      heart is a complex in vitro technique used primarily in pharmacological and
      physiological research that allows the evaluation of multiple cardiac hemodynamic
      parameters including, but not limited to, contractility and heart rate. This
      article will first provide a brief background of the Langendorff method as well
      as details regarding organ isolation. Finally, the article will discuss the
      benefits of a new technique for hanging the isolated heart aorta and the benefits
      of this technique over traditional methods.

PMID- 29204376
TI  - Mobile Cardiac Health-care Monitoring and Notification with Real Time Tachycardia
      and Bradycardia Arrhythmia Detection.
AB  - Background: The increasing trend of heart disease has turned the attention of
      researchers toward the use of portable connected technologies. The necessity of
      continuous special care for cardiovascular patients is an inevitable fact.
      Methods: In this research, a new wireless electrocardiographic (ECG) signal
      monitoring system based on smartphone is presented. This system has two main
      sections. The first section consists of a sensor which receives ECG signals via
      an amplifier, then filters and digitizes the signal, and prepares it to be
      transmitted. The signals are stored, processed, and then displayed in a mobile
      application. The application alarms in dangerous situations and sends the
      location of the cardiac patient to family or health-care staff. Results: The
      results obtained from the analysis of the electrocardiogram signals on 20
      different people have been compared with the traditional ECG in hospital by a
      cardiologist. The signal is instantly transmitted by 200 sample per second to
      mobile phone. The raw data are processed, the anomaly is detected, and the signal
      is drawn on the interface in about 70 s. Therefore, the delay is not noticeable
      by the patient. With respect to rate of data transmission to hospital, different
      internet connections such as 2G, 3G, 4G, WiFi, WiMax, or Long-Term Evolution
      (LTE) could be used. Data transmission ranges from 9.6 kbps to 20 Mbps.
      Therefore, the physician could receive data with no delay. Conclusions: A
      performance accuracy of 91.62% is obtained from the wireless ECG system. It
      conforms to the hospital's diagnostic standard system while providing a portable
      monitoring anywhere at anytime.

PMID- 29204377
TI  - Detection of Pulmonary Nodules in Low-dose Computed Tomography Using Localized
      Active Contours and Shape Features.
AB  - Background: Pulmonary nodules are symptoms of lung cancer. The shape and size of
      these nodules are used to diagnose lung cancer in computed tomography (CT)
      images. In the early stages, nodules are very small, and radiologist has to refer
      to many CT images to diagnose the disease, causing operator mistakes. Image
      processing algorithms are used as an aid to detect and localize nodules. Methods:
      In this paper, a novel lung nodules detection scheme is proposed. First, in the
      preprocessing stage, our algorithm segments two lung lobes to increase processing
      speed and accuracy. Second, template-matching is applied to detect the suspicious
      nodule candidates, including both nodules and some blood vessels. Third, the
      suspicious nodule candidates are segmented by localized active contours. Finally,
      the false-positive errors produced by vessels are reduced using some two-/three
      dimensional geometrical features in three steps. In these steps, the size, long
      and short diameters and sphericity are used to decrease the false-positive rate.
      Results: In the first step, some vessels that are parallel to CT cross-plane are
      identified. In the second step, oblique vessels are detected using shift of
      center of gravity in two successive slices. In step three, vessels vertical to CT
      cross-plane are identified. Using these steps, vessels are separated from
      nodules. Early Lung Cancer Action Project is used as a popular dataset in this
      work. Conclusions: Our algorithm achieved a sensitivity of 90.1% and a
      specificity of 92.8%, quite acceptable in comparison to other related works.

PMID- 29204378
TI  - Circular Mitochondrial DNA: A Geant4-DNA User Application for Evaluating
      Radiation-induced Damage in Circular Mitochondrial DNA.
AB  - Background: The aim of this study was to develop a nucleotide geometrical model
      of the circular mitochondrial DNA (mt-DNA) structure using Geant4-DNA toolkit to
      predict the radiation-induced damages such as single-strand breaks (SSB), double
      strand breaks (DSB), and some other physical parameters. Methods: Our model
      covers the organization of a circular human mt genetic system. The current model
      includes all 16,659 base pairs of human mt-DNA. This new mt-DNA model has been
      preliminarily tested in this work by determining SSB and DSB DNA damage yields
      and site-hit probabilities due to the impact of proton particles. The accuracy of
      the geometry was determined by three-dimensional visualization in various ring
      element numbers. The hit locations were determined with respect to a reference
      coordinate system, and the corresponding base pairs were stored in the ROOT
      output file. Results: The coordinate determination according to the algorithm was
      consistent with the expected results. The output results contain the information
      about the energy transfers in the backbone region of the DNA double helix. The
      output file was analyzed by root analyzing tools. Estimation of SSBs and DSBs
      yielded similar results with the increment of incident particle linear energy
      transfer. In addition, these values seem to be consistent with the corresponding
      experimental determinations. Conclusions: This model can be used in numerical
      simulations of mt-DNA radiation interactions to perform realistic evaluations of
      DNA-free radical reactions. This work will be extended to supercoiled
      conformation in the near future.

PMID- 29204379
TI  - The Best Texture Features for Leukocytes Recognition.
AB  - Background: Differential counting of white blood cells (WBCs or leukocytes) is a
      common task to diagnose many diseases such as leukemia, and infections. An
      accurate process for recognizing leukocytes is to evaluate a blood smear under a
      microscope by an expert. Since, this procedure is manual, time-consuming and
      tedious, making the procedure automatic would overcome these problems. In an
      automated CAD (Computer-Aided-Design) system for this purpose, a crucial module
      is leukocytes recognition. In this paper, we are looking for the best features in
      order to recognize five types of leukocytes (Monocyte, Lymphocyte, Neutrophil,
      Eosinophil and Basophil) from microscopic images of blood smear in an automated
      cell counting system. Methods: In this work, we focus on the texture features and
      seven categories: GLCM features, Haralick features, Spectral texture features,
      Wavelet-based features, Gabor-based features, CoALBP and RICLBP are analyzed to
      find the best features for leukocytes detection. The best features of each
      category are selected using stepwise regression and finally three well-known
      classifiers called K-NN, LDA and NB are utilized for classification. Results: The
      proposed system is tested on a self-provided dataset composed of 200 cell images.
      In our experiments, to evaluate the process, the accuracy of each leukocyte type
      and the mean accuracy are computed. RICLBP features achieved the best mean
      accuracy (85.53%) for LDA classifier. Conclusions: In our experiments, although
      the maximum mean accuracy (85.53%) went with RICLBP features, but the accuracies
      of all five leukocyte types weren't maximized for RICLBP features. This result
      directs us to design and develop a system based on multiple features and multiple
      classifiers to maximize the accuracies even for each individual cell type in our
      future work.

PMID- 29204380
TI  - Electrospun Polycaprolactone/lignin-based Nanocomposite as a Novel Tissue
      Scaffold for Biomedical Applications.
AB  - Background: Biopolymer scaffolds have received great interest in academic and
      industrial environment because of their supreme characteristics like biological,
      mechanical, chemical, and cost saving in the biomedical science. There are
      various attempts for incorporation of biopolymers with cheap natural micro- or
      nanoparticles like lignin (Lig), alginate, and gums to prepare new materials with
      enhanced properties. Methods: In this work, the electrospinning (ELS) technique
      as a promising cost-effective method for producing polymeric scaffold fibers was
      used, which mimics extracellular matrix structure for soft tissue engineering
      applications. Nanocomposites of Lig and polycaprolactone (PCL) scaffold produced
      with ELS technique. Nanocomposite containings (0, 5, 10, and 15 wt.%) of Lig were
      prepared with addition of Lig powder into the PCL solution while stirring at the
      room temperature. The bioactivity, swelling properties, morphological and
      mechanical tests were conducted for all the samples to investigate the
      nanocomposite scaffold features. Results: The results showed that scaffold with
      10 wt.% Lig have appropriate porosity, biodegradation, minimum fiber diameter,
      optimum pore size as well as enhanced tensile strength, and young modulus
      compared with pure PCL. Degradation test performed through immersion of samples
      in the phosphate-buffer saline showed that degradation of PCL nanocomposites
      could accelerate up to 10% due to the addition of Lig. Conclusions: Electrospun
      PCL-Lig scaffold enhanced the biological response of the cells with the
      mechanical signals. The prepared nanocomposite scaffold can choose for potential
      candidate in the biomedical science.

PMID- 29204381
TI  - A Fuzzy Controller for Movement Stabilization Using Afferent Control: Controller
      Synthesis and Simulation.
AB  - Stimulation of spinal sensorimotor circuits can improve motor control in animal
      models and humans with spinal cord injury (SCI). More recent evidence suggests
      that the stimulation increases the level of excitability in the spinal circuits,
      activates central pattern generators, and it is also able to recruit distinctive
      afferent pathways connected to specific sensorimotor circuits. In addition, the
      stimulation generates well-defined responses in leg muscles after each pulse. The
      problem is that in most of the neuromodulation devices, electrical stimulation
      parameters are regulated manually and stay constant during movement. Such a
      technique is likely suboptimal to intercede maximum therapeutic effects in
      patients. Therefore, in this article, a fuzzy controller has been designed to
      control limb kinematics during locomotion using the afferent control in a
      neuromechanical model without supraspinal drive simulating post-SCI situation.
      The proposed controller automatically tunes the weights of group Ia afferent
      inputs of the spinal cord to reset the phase appropriately during the reaction to
      an external perturbation. The kinematic motion data and weights of group Ia
      afferent inputs were the input and output of the controller, respectively.
      Simulation results showed the acceptable performance of the controller to
      establish adaptive locomotion against the perturbing forces based on the phase
      resetting of the walking rhythm.

PMID- 29204382
TI  - Effect of Material and Wall Thickness Buildup Caps on the Head Scatter Factor
      Measurements in Irregular Fields Shielded by Cerrobend.
AB  - The head scatter factor (Sc ) is important to measurements radiation beam and
      beam modeling of treatment planning systems used for advanced radiation therapy
      techniques. This study aimed to investigate the design of a miniphantom to
      measurement variations in collimator Sc in the presence of shielding blocks for
      shaping the beam using different field sizes. Copper, Brass, and Perspex buildup
      caps were designed and fabricated locally as material with three different
      thicknesses for buildup caps (miniphantoms). Measurements were performed on an
      Elekta Compact medical linear accelerator (6 MV) in Shafa Kerman Hospital, Iran.
      The Farmer-type ion chamber FG65-P (Scanditronix, Wellhofer) was used for all
      measurements. To measure the Sc , miniphantom was positioned in a stand vertical
      to the beam central axis. The data indicate that the Sc measurements using
      different buildup cap materials and thicknesses in 5 * 10, 7.5 * 7.5, and two 10
      * 10 cm Cerrobend shield blocks ranged 0.98 to 1.00, 1.04 to 1.05, and 1.04 to
      1.06, respectively. Also, it was observed that by increasing the block shield
      area from 50 cm2 to both 56.25 and 100 cm2, the Sc increased in all situations.
      Results showed that using Brass compared to Perspex and Copper has less
      uncertainty due to its simple preparation and cutting which is useful to
      measurement of variations in collimator Sc and shaping the photon beam.

PMID- 29204383
TI  - Hand-arm Vibration Effects on Performance, Tactile Acuity, and Temperature of
      Hand.
AB  - Effects of vibration appear as mechanical and psychological disorders, including
      stress reactions, cognitive and movement disorders, problem in concentration and
      paying attention to the assigned duties. The common signs and symptoms of hand
      arm vibration (HAV) in the fingers and hands may appear as pins and needles
      feeling, tingling, numbness, and also the loss of finger sensation and dexterity.
      Laboratory Virtual Instrument Engineering Workbench programming software designed
      for occupational vibrations measurement was used to calculate HAV acceleration.
      Hole steadiness test is designed to measure involuntary movement of people. V
      Pieron test is designed for one of the other aspects of the psycho motor
      phenomena of steadiness by moving the stylus across a V-form ruler. The two
      points test was an experiment of touch acuity, which used a caliper by placing
      the two styli very close on the pad of finger knuckles. The temperature of finger
      skin is also measured simultaneous to the above tests. Wilcoxon test indicated
      that a significant decrement in hand steadiness occurred after gripping a
      vibrating handle for 2 min (P <= 0.003). Wilcoxon test also represented a
      significant change in errors after gripping a grinder vibratory handle (P <=
      0.003). The differences at all of the knuckles were significant with a confidence
      interval percentage of 99%. There was a significant reduction in finger skin
      temperature before and after exposure to vibration (mean = 0.45 degrees C, based
      on paired sample test). The obtained results considerably demonstrated the
      relation between hand performance and vibrations due to gripping a grinder. It
      can be concluded that an injury or accident may happen after exposure to
      vibrations for the fine duties, in fast actions.

PMID- 29204384
TI  - Approach to a Child with Primary Immunodeficiency Made Simple.
AB  - Primary immunodeficiency disorders (PIDs) are a group of disorders affecting the
      capability to fight against infection. These include defects in T cells and B
      cells affecting cell-mediated and humoral immunity, respectively, combined
      humoral and cell-mediated immunodeficiency, defects in phagocytosis, complement
      defects, and defects in cytokine or cytokine signalling pathways which are
      detrimental for immune function. Depending upon the type and severity, age at
      onset of symptoms can vary from neonatal period to late childhood. Clinically,
      this group of disorders can involve any organ system of an individual such as
      respiratory system, gastrointestinal system, skin and mucous membrane, bone and
      joints, endocrine organs, and nervous system. Common dermatological
      manifestations include eczema, warts, molluscum contagiosum, mucocutaneous
      candidiasis, recurrent nonhealing ulcers, skin abscesses, erythroderma,
      petechiae, and nail changes. The common skin manifestations of various PIDs
      include eczema (seen in Wiskott-Aldrich syndrome and autosomal dominant hyper IgE
      syndrome); erythroderma (in Omen syndrome); viral warts or molluscum contagiosum
      (in autosomal recessive hyper IgE syndrome); chronic mucocutaneous candidiasis
      (in hyper IgE syndrome, autoimmune polyendocrinopathy candidiasis ectodermal
      dysplasia syndrome, Th17 cell defects); recurrent nonhealing ulcers (in leucocyte
      adhesion defect); skin abscesses (in antibody defects, hyper IgE syndrome, and
      chronic granulomatous disease); petechial or purpuric spots (in Wiskott-Aldrich
      syndrome).

PMID- 29204386
TI  - Identification of Genotypes and Allelic Frequencies of Vitamin D Receptor Gene
      Polymorphism (TaqI) in Egyptian Melasma Patients.
AB  - Background: Melasma is a characteristic pattern of facial hyperpigmentation,
      occurring primarily on the forehead, cheeks, and chin, in a mask-like
      distribution. The pathogenesis of melasma is not fully understood. Vitamin D
      plays a role in skin pigmentation. It exerts its effect through vitamin D
      receptor (VDR), which is expressed in variable cells including normal
      melanocytes. Aim and Objective: The aim of the current work was to investigate if
      VDR gene polymorphism (TaqI) confers susceptibility to melasma in Egyptian
      patients. Materials and Methods: A total of 45 female patients with melasma were
      recruited and 50 healthy subjects that were matched on age, sex, body mass index,
      and skin phototype, were included as a control group. TaqI polymorphism was
      investigated using restriction fragment length polymorphism polymerase chain
      reaction (RFLP PCR). Results: Presence of (t) allele and (tt) genotype was
      significantly associated with melasma cases compared with control group (P <
      0.001 for both). No significant association was found between (tt) genotype or
      (t) allele and clinical data of the studied cases. Conclusion: TaqI polymorphism
      is associated with melasma. Further, large-scale studies are recommended to
      underscore and validate the current findings. It is also necessary for future
      studies to extend the research to other populations and ethnicities.
      Investigating other VDR gene polymorphisms in melasma is also warranted. Since
      melasma is a multifactorial disease, gene-gene and gene-environment interactions
      should be considered in future genetic-epidemiologic researches to apply more
      comprehensive insight into the role of VDR gene in its pathogenesis.

PMID- 29204387
TI  - Pattern of Skin Diseases and Occupational Dermatoses in Veterinarians and
      Veterinary Workers of Kashmir.
AB  - Background: Across the globe, skin disorders represent a frequent occupational
      concern for many health professionals including veterinarians and there is a
      serious impact of skin diseases on their lives and careers. But little is known
      about the prevalence and distribution of skin diseases (especially occupational)
      within this important professional group across Asia, especially India. Materials
      and Methods: The study was a cross-sectional study carried out over a period of
      one year in which veterinarians and veterinary workers of Kashmir valley were
      screened for various skin diseases and occupational dermatoses. Results: The
      study group comprised 910 veterinarians and associated workers working across the
      valley with the majority being males; 846 workers (93%). The mean age of the
      group was 38.53 years. Out of these, 267 veterinarians and associated workers
      (29.3%) were found to have skin lesions. Of the 267 cases, 165 (61.80%) had non
      infectious lesions, while the rest had 102 (38.20%) had infectious skin diseases.
      The main non-infectious lesions included friction-related disorders, eczemas,
      pigmentary disorders, papulosquamous disorders, and many others; while the
      infectious lesions were of fungal, bacterial, viral, and parasitic etiology.
      Fungal infections, eczemas, and melasma were more common in them, indicating an
      occupational etiology. Conclusion: A huge group of skin diseases was seen in
      veterinarians and veterinary workers, with some diseases showing an occupational
      nature. To reduce the burden of skin diseases in this particular group, proper
      prevention measures need to be instituted at work places by veterinary governing
      bodies of the state.

PMID- 29204385
TI  - Evidence-based Review, Grade of Recommendation, and Suggested Treatment
      Recommendations for Melasma.
AB  - Treatment of melasma is known to be less satisfactory, often incomplete, and
      relapse is frequent. Although many treatment options are available, they are
      either known to be unsafe on long-term use or their long-term safety profile is
      unknown. Patients often use various drugs, even topical steroid-based preparation
      without any medical supervision for long period of time, making the skin
      unsuitable for many of the drugs available. Thus, there has been gross disparity
      among the treating physician about what drugs and what regimen are best suitable
      for various categories of melasma patients and in different situations. With this
      background, numerous newer drugs, mostly combinations of some proprietary
      molecules or even unknown plant extracts, have flooded the market for the
      management of melasma. Information on efficacy or safety of these products are
      almost unknown. Studies on Asian people, especially Indian population, are far
      less commonly available. Therapeutic guideline for use on Indian patients with
      melasma is almost missing. Extrapolation of data from Caucasian people for use on
      Asian people may not be scientifically justifiable because Caucasian and Asian
      people are known to have inherent difference in their response as well as
      tolerance to the drugs used for melasma. With this background, we have
      extensively evaluated, following a strict, scientifically designed protocol, all
      the available studies on melasma management till May 2016 and prepared this
      document on level of evidence, grade of recommendation and suggested therapeutic
      guideline for melasma as per the method proposed by Oxford Centre of Evidence
      Based Medicine. Various ethical, social, logical, regional, and economic issues
      in the context of Indian and similar populations were given due importance while
      preparing the suggested therapeutic recommendation.

PMID- 29204388
TI  - Clinic-based Group Multi-professional Education Causes Significant Decline in
      Psoriasis Severity: A Randomized Open Label Pilot Study.
AB  - Background: The evidence for efficacy of psychoeducational interventions in
      psoriasis is not well researched. Objective: The objective of this study was to
      assess the benefits of a group, multi-professional, psychoeducational training in
      psoriasis. Materials and Methods: Adults with moderate-to-severe psoriasis were
      randomized into psychoeducational intervention plus treatment (intervention arm
      [IA]) and treatment as usual alone (control arm [CA]) groups using random number
      tables. The primary efficacy measures were mean changes in Psoriasis Area
      Severity Index (PASI) and Dermatology Life Quality Index (DLQI) at 6months from
      the end of intervention. The secondary efficacy measures were the mean changes in
      the WHO-5 well-being index (WHO-5) and the subsets of the patient health
      questionnaire (PHQ), namely, PHQ-9, generalized anxiety disorder (GAD)-7, andPHQ
      15. Datawere analyzed by intention-to-treat analysis. Results: One-hundred and
      three participants were randomized into IA (n = 54) and CA (n = 49). The
      prevalence of psychiatric disorders in the entire population was 26.2% and was
      similar in both groups. Following intervention, there was statistically
      significant improvement in the mean scores in PASI, DLQI, and WHO-5 in the IA
      unlike that seen in the CA. There was statistically significant improvement in
      PHQ-9 scores in IA and CA. The scores on PHQ-15 and GAD-7 did not show any
      change. Intergroup comparisons showed that PASI was reduced significantly in IA
      as compared to CA. More participants in CA dropped out of the study than in the
      IA. Limitations: Modest sample size and lack of blinding of the participants and
      the administrators were the limitations of this study. Conclusion: Group
      psychoeducational intervention resulted in overall improvement in both clinical
      and psychological outcome measures in psoriasis patients.

PMID- 29204390
TI  - Platelet-rich Plasma by Single-spin Process in Male Pattern Androgenetic
      Alopecia: Is it an Effective Treatment?

PMID- 29204389
TI  - Platelet-rich Plasma by Single Spin Process in Male Pattern Androgenetic
      Alopecia: Is it an Effective Treatment?
AB  - Introduction and Objective: Platelet-rich plasma (PRP) is an autologous
      preparation of platelets in concentrated plasma. The platelet is a natural source
      of different growth factors and cytokines. These growth factors act on stem cells
      in the bulge area of the follicles and stimulate the development of new
      follicles, and promote neovascularization. The aim of this study was to
      investigate the efficacy and safety of PRP injections in androgenetic alopecia
      (AGA) in men. Patients and Methods: Fifteen male patients (mean age: 39 +/- 9.7
      years) with AGA grades III-VI were enrolled in the study. Five injections of 2-4
      ml PRP (Regenlab PRP Kit-RegenACR(r), Le Mont-sur-Lausanne Switzerland) by single
      spin process were administered every 2 weeks. Standard photographs, trichogram,
      and measurement of hair density and diameter in an area marked with a tattoo
      (with digital photographic hair analyzer) were done at baseline and 3 months
      after the last injection. In addition, patients completed a patient satisfaction
      questionnaire at each visit on a -2 to +2 score (-2: much worse, -1: slightly
      worse, 0: without change, +1: slightly better, +2: much better). Results:
      Thirteen patients completed the study. The number of hairs increased slightly
      from 149.62 +/- 49.56 to 168.46 +/- 43.703/cm2, however, this increase was not
      statistically significant (P = 0.24). On the other hand, the thickness of hairs
      decreased from 0.051 +/- 0.105 to 0.045 +/- 0.011 mm, which was also not
      significant (P = 0.37). There was a significant decrease in anagen hairs and
      increase in telogen hairs, and anagen/telogen ratio decreased significantly from
      6.38 +/- 4.57 to 2.67 +/- 1.87 (P = 0.003). Conclusion: Our study could not show
      any benefit from PRP injections in the treatment of male AGA. There is a strong
      need for well-designed, randomized controlled trials with large sample size,
      proper control group, standard treatment protocols (concerning the amount, number
      and interval of PRP injections, method of preparation and activation, etc.), and
      long follow-up periods to evaluate the safety and efficacy of PRP in the
      treatment of male AGA.

PMID- 29204391
TI  - Mean Platelet Volume: A Reliable Marker of Inflammation in Recurrent Apthous
      Stomatitis and Behcet Disease?
AB  - Background: Mean platelet volume (MPV) is an indicator of platelet activation and
      aggregation. MPV has been found to be related with the inflammation of certain
      disorders in recent studies. Aims: We sought to investigate whether MPV could be
      an indicator of inflammation in patients with Behcet disease (BD) and recurrent
      apthous stomatitis (RAS). Materials and Methods: Our study was designed as a
      retrospective case-control study and data was retrieved from our institutional
      database. We randomly generated a total of three study groups from our clinical
      archive. All controls were sex and age-matched and randomly selected by computer.
      Eighty-five patients with BD, 82 patients with RAS, and 721 healthy controls were
      included for the study design. We compared mean MPV values in the patient groups
      and controls. Results: We found no difference in the mean MPV value between BD
      group and BD-control group. The mean MPV value was significantly higher in
      patients with RAS than that in the RAS-control group (9.11 +/- 1.01 fL vs. 8.76
      +/- 1.15 fL, P = 0.045). There was no difference in mean MPV level between BD and
      RAS group. Conclusion: The association between MPV and inflammatory skin diseases
      such as BD and RAS should be investigated prospectively in case-control studies.
      Limitations: Retrospective study design.

PMID- 29204392
TI  - Subungual Melanoma is Not so Rare: Report of Four Cases from India.
AB  - Subungual melanoma (SUM) is an uncommon form of acral melanoma that arises within
      the nail matrix. The incidence for acral melanomas is similar worldwide, however,
      the proportion is higher in dark-skinned individuals. The subungual form
      represents approximately 2% of cutaneous non-sun-induced melanomas in the western
      world and up to 75% in Africans, 10% in Japanese, and 25% in the Chinese. No
      specific figures are available from the Indian subcontinent; however, the authors
      could trace three anecdotal case reports published over the last two decades. A
      general reluctance to biopsy a nail lesion to confirm the diagnosis may be
      contributing to the missed diagnosis. We report four cases of SUM of the big
      toenails seen over a period of 2.5 years. They were three women and one man with
      an age ranging from the 4th to 7th decade and disease duration of 6-18 months.
      The lesion involved the big toe in all and two patients had liver and lymph node
      metastasis at the time of presentation. Awareness among dermatologists regarding
      clinical manifestations, high index of suspicion for acral pigmented lesions, and
      nail bed biopsy may help in the early diagnosis and management and can prevent
      mortality.

PMID- 29204393
TI  - Lymphocutaneous Sporotrichosis Treated with Potassium Iodide with Development of
      Subclinical Hypothyroidism: Wolff-Chaikoff Effect?
AB  - Sporotrichosis is a subcutaneous mycotic infection caused by Sporothrix schenckii
      that is acquired by traumatic implantation. The diagnosis is established by
      demonstration of fungal elements on histopathology and culture. Potassium iodide,
      azole antifungals, and terbinafine are the treatment options available. In this
      article, we report a 60-year-old female with lymphocutaneous sporotrichosis that
      responded well to potassium iodide. However, subclinical hypothyroidism (Wolff
      Chaikoff effect) was encountered as a side effect of therapy which was managed
      with thyroxine replacement. Knowledge about the Wolff-Chaikoff effect (WCE) is
      important for the dermatologist and reinforces the need for screening and
      monitoring of thyroid stimulating hormone (TSH) in patients where long duration
      therapy is being planned.

PMID- 29204394
TI  - Paraneoplastic Pemphigus with Underlying Retroperitoneal Inflammatory
      Myofibroblastic Tumor: A Case Report and Review of the Literature.
AB  - Inflammatory myofibroblastic tumor (IMT) is a peculiar low-grade neoplasm of
      spindle cell fibroblasts and myofibroblasts in an inflammatory background. The
      lung is the most common site of involvement. Here, we report a case of
      paraneoplastic pemphigus (PNP)-associated with an extensive retroperitoneal IMT.
      The patient had a favourable response following treatment with a low dose of
      systemic steroid, mycophenolate mofetil, and intravenous immunoglobulin (IVIG).
      He subsequently underwent surgery for resection of the tumor with nephrectomy and
      five courses of IVIG were administered after surgery due to a minor relapse. He
      was in remission in her last follow-up visit 16 months after surgery. The
      occurrence of PNP with IMT is notable; early detection and treatment are crucial
      for this tumor-associated autoimmune disease.

PMID- 29204396
TI  - Development of a Simple Smartphone Adapter for Digital Photomicrography.

PMID- 29204395
TI  - Mutilating Keratoderma with Concomitant Alopecia and Keratoses Follicularis
      Spinulosa Decalvans: X-Linked Olmsted Syndrome and its Response to Isotretinoin.
AB  - We report a case of mutilating keratoderma with alopecia and keratoses
      follicularis spinulosa decalvans (KFSD), which was initially diagnosed as
      ectodermal dysplasia and Olmsted syndrome but was revisited as a case of X-linked
      Olmsted (XLO) syndrome. We focus on this uncommon entity (XLO) to highlight the
      differentials of alopecia with palmoplantar keratoderma.

PMID- 29204397
TI  - Follicular Dowling-Degos Disease: A Rare Pigmentary Dermatosis.

PMID- 29204398
TI  - Adult-onset Hydroa Vacciniforme: A Rare Occurrence or a Lymphoma Premonition?

PMID- 29204399
TI  - Cutaneous angiosarcoma of scalp.

PMID- 29204401
TI  - Dermatofibrosarcoma Protuberans.

PMID- 29204400
TI  - Current Scenario of Childhood Leprosy at a Tertiary Care Hospital in Southern
      Rajasthan.

PMID- 29204402
TI  - Blaschko-linear Syringocystadenoma Papilliferum: A Peculiar Presentation.

PMID- 29204403
TI  - Immunofluorescence and Immunohistochemistry in Macular Amyloidosis: An
      Observational Study.

PMID- 29204404
TI  - Symmetric Drug-related Intertriginous and Flexural Exanthema due to Itraconazole:
      An Uncommon Side Effect of a Commonly Used Drug.

PMID- 29204405
TI  - Pseudoverrucous Papules and Nodules in an Infant with Penoscrotal Hypospadiasis.

PMID- 29204406
TI  - Acquired smooth muscle hamartoma of foot: A rare entity.

PMID- 29204407
TI  - Giant Chronic Cutaneous Leishmaniasis: Case Report of an Unusual.

PMID- 29204408
TI  - Necrotic Erythema Nodosum Leprosum Healing with Extensive Scars.

PMID- 29204409
TI  - Papular Granuloma Annulare of Palms and Soles.

PMID- 29204410
TI  - Noise Removal in Dermoscopic Images Using a Novel Software.

PMID- 29204411
TI  - Utility of Direct Immunofluorescence in the Diagnosis of Small Vessel Vasculitis
      of the Skin: A Cross-Sectional Study.

PMID- 29204412
TI  - SkIndia Quiz 42: Multiple Slow-growing Papulonodular Lesions Over the Nose.

PMID- 29204413
TI  - Smegma pearl.

PMID- 29204414
TI  - Gardner diamond syndrome: A psychogenic purpura.

PMID- 29204415
TI  - Dermoscopy of Pyogenic Granuloma.

PMID- 29204416
TI  - Dermoscopy of Melasma.

PMID- 29204417
TI  - Dermatophytosis: Fighting the Challenge: Conference Proceedings and Learning
      Points. September 2-3, 2017, PGIMER, Chandigarh, India.

PMID- 29204418
TI  - Comparison between anterior segmental osteotomy versus conventional orthodontic
      treatment in root resorption: a radiographic study using cone-beam computed
      tomography.
AB  - Background: Patients who received orthodontic treatment are likely to have apical
      root shortening. It appears that external apical root resorption results from a
      combination of patient-related risk factors such as genetic influences, systemic
      factors, and orthodontic treatment-related factors. Regarding the fact that the
      anterior segmental osteotomy (ASO) has been known for its possibility of
      complementing external apical root resorption and of buffering periodontal
      problems, it has been the preferred treatment. However, the studies on the
      efficacy of ASO in preserving the root are not sufficient. In this study, we
      compared the amount of root resorption between the patients who only received
      orthodontic treatment and the patients who received orthodontic treatment with
      ASO. Methods: This study included 28 patients (the number of incisor = 198) who
      received orthodontic treatment with or without ASO. We categorize them into
      groups A and B by the type of orthodontic treatment (group A: conventional
      orthodontic treatment; group B: orthodontic treatment with ASO). Cone-beam
      computed tomographic and cephalometric evaluations were retrospectively performed
      on the radiographs taken for the diagnosis of the treatment before treatment and
      at the end of active treatment. Results: In group B, root resorption itself and
      its rate both turned out to have significantly lower than those in group A. Also,
      the change of incisal angle is significantly smaller in group B than in group A.
      On the other hand, in group A, the change of incisal angle was positively
      correlated with the change of AP (anteroposterior) position. In group B, the
      change of incisal angle was negatively correlated with the duration of the
      orthodontic treatment. In group B, amount of root resorption (mm) was positively
      correlated with the duration of the orthodontic treatment. Conclusions: The
      results show lesser root resorption and shorter treatment duration with ASO than
      with conventional orthodontic treatment. Therefore, if the indications are
      accurately determined, ASO can be an effective treatment option when the amount
      of root resorption is expected to be high, especially in late adults.

PMID- 29204419
TI  - Treatment of dental implant displacement into the maxillary sinus.
AB  - Background: Displacement of dental implants into the maxillary sinus is rare, but
      it primarily occurs in patients with severe pneumatization of the maxillary sinus
      and/or deficiency of the alveolar process. Some complications such as the
      infection of the paranasal sinuses and formation of the oroantral fistula can be
      followed by the displacement of a dental implant. Therefore, the displaced
      implant has to be removed immediately with surgical intervention show and another
      plan for rehabilitation should be considered. Main body: The conventional
      procedure for the removal of a displaced implant from the maxillary sinus
      involves sinus bone grafting and new implant placement performed in two or more
      steps with a significant time gap in between. Simplification of these surgical
      procedures can decrease the treatment duration and patient discomfort.
      Conclusions: In this review, we discuss the anatomical characteristics of the
      maxillary sinus and the complications associated with implant displacement into
      the sinus.

PMID- 29204420
TI  - Editorial: International Perspectives on Health and Safety among Dairy Workers:
      Challenges, Solutions and the Future.

PMID- 29204421
TI  - Weight-Related Barriers for Overweight Students in an Elementary Physical
      Education Classroom: An Exploratory Case Study with One Physical Education
      Teacher.
AB  - Introduction: As physical performance may be more difficult for overweight
      children than for their non-overweight peers, understanding how weight impacts
      student performance in the physical education (P.E.) classroom could inform
      school-based obesity prevention programming. Materials and methods: This
      qualitative case study examined one elementary physical educator's perspectives
      of overweight students' weight-related experiences in her classroom. Narratives
      were elicited during an in-depth interview and analyzed using structural and
      thematic analyses. We utilized the social cognitive theory to inform our
      exploration of the narratives. Findings: The thematic analysis illuminated a
      behavioral pattern of student refusal to participate in the P.E. classroom while
      the structural analysis emphasized the teacher's constructive, individualized
      responses to participation refusals. Combined, the two analytic techniques
      provided a more holistic snapshot of the experiences of overweight students in
      this elementary school. In addition, a preliminary model explaining the
      behavioral pattern among overweight students in this particular P.E. classroom
      was created. Discussion: Students who were overweight were more likely to
      initially refuse to attempt physical tasks in the classroom because they feared
      peer ridicule, and the teacher played a critical role in whether these students
      chose to participate in subsequent classes. As agents of change, P.E. educators
      should be included in formative stages of comprehensive, systemic changes to
      combat childhood obesity.

PMID- 29204422
TI  - Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in
      Silico Modeling and Virtual Screening Strategies to Combat Early Blight.
AB  - Alternaria blight is an important foliage disease caused by Alternaria solani.
      The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of
      its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH
      enzyme could be efficient tool to design novel fungicides against A. solani. We
      employed computational methodologies to design new SDH inhibitors using homology
      modeling; pharmacophore modeling and structure based virtual screening. The three
      dimensional SDH model showed good stereo-chemical and structural properties.
      Based on virtual screening results twelve commercially available compounds were
      purchased and tested in vitro and in vivo. The compounds were found to inhibit
      mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory
      effects were enhanced with increase in concentrations. Similarly increased
      disease control was observed in pre-treated potato tubers. Hence the applied in
      silico strategy led us to identify novel fungicides.

PMID- 29204423
TI  - Dual Coating of Liposomes as Encapsulating Matrix of Antimicrobial Peptides:
      Development and Characterization.
AB  - Antimicrobial peptides have been proposed as a potential biopreservatives in
      pharmaceutical research and agribusiness. However, many limitations hinder their
      utilization, such as their vulnerability to proteolytic digestion and their
      potential interaction with other food ingredients in complex food systems. One
      approach to overcome such problems is developing formulations entrapping and
      thereby protecting the antimicrobial peptides. Liposome encapsulation is a
      strategy that could be implemented to combine protection of the antimicrobial
      activity of the peptides from proteolytic enzymes and the controlled release of
      the encapsulated active ingredients. The objective of this study was to develop
      dual-coated food grade liposome formulations for oral administration of
      bacteriocins. The formulations were developed from anionic and cationic
      phospholipids as models of negatively and positively charged liposomes,
      respectively. Liposomes were prepared by the hydration of lipid films.
      Subsequently, the liposomes were coated with two layers comprising a biopolymer
      network (pectin) and whey proteins (WPI) in order to further improve their
      stability and enable the gradual release of the developed liposomes. Liposomes
      were characterized for their size, charge, molecular structure, morphology,
      encapsulation efficiency, and release. The results of FTIR, zeta potential, size
      distribution, and transmission electron microscopy (TEM) confirmed that the
      liposomes were efficiently coated. Ionic interactions were involved in the
      stabilization of the positively charged liposome formulations. Negatively charge
      liposome formulations were stabilized through weak interactions. The release
      study proved the efficiency of dual coating on the protection of liposomes
      against gastrointestinal digestion. This work is the first to study the
      encapsulation of antimicrobial peptides in dual-coated liposomes. Furthermore,
      the work successfully encapsulated MccJ25 in both negative and positive liposome
      models.

PMID- 29204425
TI  - Continuous Non-Invasive Arterial Pressure Assessment during Surgery to Improve
      Outcome.
AB  - Blood pressure (BP) is one of the most important variables evaluated during
      almost every medical examination. Most national anesthesiology societies
      recommend BP monitoring at least once every 5 min in anesthetized subjects
      undergoing surgical procedures. In most cases, BP is monitored non-invasively
      using oscillometric cuffs. Although the risk of arterial cannulation is not very
      high, the invasive BP monitoring is usually indicated only in the case of high
      risk patients or in complex surgical procedures. However, recent evidence points
      out that when using intermittent BP monitoring short periods of hypotension may
      be overlooked. In addition, large datasets have demonstrated that even short
      periods of low BP (or their cumulative duration) may have a detrimental impact on
      the development of postoperative outcome including increased risk of acute kidney
      or myocardial injury development. Recently marketed continuous non-invasive blood
      pressure monitoring tools may help us to recognize the BP fluctuation without the
      associated burden of arterial cannulation filling the gap between intermittent
      non-invasive cuff and continuous invasive arterial pressure. Among others,
      several novel devices based either on volume clamp/vascular unloading method or
      on applanation tonometry are nowadays available. Moreover, several near-future
      smart technologies may lead to better hypotension recognition or even prediction
      potentially improving our ability to maintain BP stability throughout the
      anesthesia or surgical procedure. In this review, novel or emerging technologies
      of non-invasive continuous blood pressure assessment and their potential to
      improve postoperative outcome are discussed.

PMID- 29204424
TI  - 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug
      Screening.
AB  - Neurodegenerative diseases affect millions of individuals in North America and
      cost the health-care industry billions of dollars for treatment. Current
      treatment options for degenerative diseases focus on physical rehabilitation or
      drug therapies, which temporarily mask the effects of cell damage, but quickly
      lose their efficacy. Cell therapies for the central nervous system remain an
      untapped market due to the complexity involved in growing neural tissues,
      controlling their differentiation, and protecting them from the hostile
      environment they meet upon implantation. Designing tissue constructs for the
      discovery of better drug treatments are also limited due to the resolution needed
      for an accurate cellular representation of the brain, in addition to being
      expensive and difficult to translate to biocompatible materials. 3-D printing
      offers a streamlined solution for engineering brain tissue for drug discovery or,
      in the future, for implantation. New microfluidic and bioplotting devices offer
      increased resolution, little impact on cell viability and have been tested with
      several bioink materials including fibrin, collagen, hyaluronic acid,
      poly(caprolactone), and poly(ethylene glycol). This review details current
      efforts at bioprinting neural tissue and highlights promising avenues for future
      work.

PMID- 29204426
TI  - Burden among Family Caregivers of Dementia in the Oldest-Old: An Exploratory
      Study.
AB  - Background: With >85 years, the fastest growing age segment in developed
      countries, dementia in the oldest-old is projected to increase exponentially.
      Being older, caregivers of dementia in oldest-old (CDOO) may experience unique
      challenges compared with younger-age groups. Thus, we aim to explore demographic
      characteristics and burden pattern among CDOO. Methods: We studied 458 family
      caregiver-patient dyads attending an outpatient memory clinic. We classified
      patients into three age-groups: <75, 75-84, and >=85 years. We measured caregiver
      burden using the Zarit Burden Interview (ZBI) 4-factor structure described by
      Cheah et al. (1). We compared care recipient characteristics, caregiver
      demographics, and ZBI total/factors scores between the three age-groups, and
      performed 2-way analysis of variance (ANOVA) to ascertain the effect of age-group
      by disease severity interaction. Results: Oldest-old care recipients were more
      impaired in cognitive function and instrumental ADL; there was no difference in
      behavior and basic ADL. Compared with the other two age-groups, CDOO were older
      (mean age: 50.4 vs 55.5 vs 56.8 years, P < 0.01), and overwhelmingly adult
      children (85.9%) as opposed to spouses (5.3%). CDOO also had higher ZBI total
      score, role strain, and personal strain (all P < 0.05). However, there was no
      difference in worry about performance scores. 2-way ANOVA did not reveal
      significant age-group by disease severity interaction for ZBI total and factor
      scores, although distinctive differences were seen between role/personal strain
      with worry about performance in mild cognitive impairment and very mild dementia.
      Conclusion: Our study highlighted that CDOO were mainly older adult children who
      experienced significant role and personal strain independent of disease severity
      while caring for their family member with more impaired cognitive and physical
      function. These results pave the way for targeted interventions to address the
      unique burden faced by this rapidly growing group of caregivers.

PMID- 29204427
TI  - Natural killer cells activity in a metastatic colorectal cancer patient with
      complete and long lasting response to therapy.
AB  - Here we report a case of a 70-year-old man who received adjuvant chemotherapy
      with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a
      stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal
      lymphnodes metastases evidenced by positron emission tomography- computed
      tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level.
      Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April
      2012. Restaging showed a complete response and normalization of CEA. The patient
      received maintenance therapy with bevacizumab which was stopped in December 2013
      for patient choice. In October 2014, a new increase in CEA was documented and PET
      CT scan showed lung metastases. Analysis of RAS status revealed the absence of
      mutations, then the patient started a second-line chemotherapy with
      fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in
      January 2015, a complete response and normalization of CEA. Thereafter, folfiri
      was discontinued for toxicity; furthermore, upon the third occurrence of a grade
      3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the
      original dose and it was administered every three weeks. Until presentation of
      this case, the patient maintains a complete response, has no symptoms of disease
      and CEA is normal. Interestingly, this patient presented a high proportion of
      circulating natural killer (NK) cells (35.1%) with high cytotoxic activity
      against tumor cells. Study on the role of NK in patients with advanced colorectal
      cancer are ongoing.

PMID- 29204428
TI  - Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic
      pathway.
AB  - Here, we report a case of gastric neuroendocrine carcinoma showing an interesting
      tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric
      tenderness, and distal gastrectomy was performed. In the surgical specimen,
      histologically, the tumor tissue was composed of three subtypes of tumor
      components showing different histological architecture and cellular atypia,
      diagnosed as neuroendocrine tumor (NET) G2, NET G3, and neuroendocrine carcinoma
      (NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET
      G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic
      imbalance (AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22q was commonly found in
      all components, AI of 4p was found in NET G3 and NEC components (but not in the
      NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC
      component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within
      the same tumor.

PMID- 29204429
TI  - Acid suppressive therapy improved symptoms due to circumferential cervical inlet
      patch with proton pumps (H+/K+-ATPase).
AB  - Cervical inlet patch (CIP), also referred to as esophageal heterotopic gastric
      mucosa, is regarded as the residue of columnar epithelium of the embryonic
      esophagus. Narrow band imaging increases the detection rate of CIP. Herein, we
      present a 55-year-old man with symptomatic circumferential inlet patch. He
      exhibited globus and dysphagia, and esophagogastroduodenoscopy found cir
      cumferential CIP, where im-munohistochemistry revealed the existence of pro-ton
      pumps (H+, K+-ATPase). His throat symptoms were relieved by acid suppressive
      therapy with pump inhibitors. This case indicated that CIP should be considered
      as a differential diagnosis for the cause of globus symptoms in rare cases.

PMID- 29204430
TI  - Carbamylation/citrullination of IgG Fc in bronchiectasis, established RA with
      bronchiectasis and RA smokers: a potential risk factor for disease.
AB  - Bronchiectasis (BR) and smoking are risk factors for rheumatoid arthritis (RA)
      development. The mechanisms by which smoking and BR trigger RA are unknown, but
      are associated with concurrent rheumatoid factor (RF) and anti-cyclic
      citrullinated peptide antibody (anti-CCP) positivity. Anti-carbamylated protein
      antibodies (anti-CarP) have also been observed in BR patients and can be induced
      by smoking. Given that RF only has one antigen, immunoglobulin G (IgG) we have
      suggested that post-translational modifications to the Fc region of the heavy
      chain of IgG (IgGH) are a potential explanation for the clustering of the RA
      associated autoantibodies in RA. Protein analysis was undertaken on 22
      individuals. Four of the individuals had a diagnosis of BR at the time of protein
      analysis and subsequently developed RA up to 18 months following blood sampling.
      Four smoking RA patients and 4 patients with both BR and RA and 10 healthy
      controls were also studied. We identified modified arginines (Arg) frequently in
      the variable region and CH3 domains of IgG in patients and control subjects
      alike, but only observed carbamylated Lys and/or citrullinated Arg modifications
      in the RF binding site of the IgG CH2 domain of 5/12 (41.7%) patients
      investigated (1 BR, 2 RA and 2 BRRA), but in no control subjects (0/10, 0%)
      p=0.02. This is the first report of citrullination and carbamylation at the RF
      binding site of IgG in RA. These results point towards the concept of a universal
      antigen in RA, an antigen that is post-translationally modified at the Fc region
      of IgGH.

PMID- 29204431
TI  - Efficacy of ventilator waveform observation for detection of patient-ventilator
      asynchrony during NIV: a multicentre study.
AB  - The objective of this study was to assess ability to identify asynchronies during
      noninvasive ventilation (NIV) through ventilator waveforms according to
      experience and interface, and to ascertain the influence of breathing pattern and
      respiratory drive on sensitivity and prevalence of asynchronies. 35 expert and 35
      nonexpert physicians evaluated 40 5-min NIV reports displaying flow-time and
      airway pressure-time tracings; identified asynchronies were compared with those
      ascertained by three examiners who evaluated the same reports displaying,
      additionally, tracings of diaphragm electrical activity. We determined: 1)
      sensitivity, specificity, and positive and negative predictive values; 2) the
      correlation between the double true index (DTI) of each report (i.e., the ratio
      between the sum of true positives and true negatives, and the overall breath
      count) and the corresponding asynchrony index (AI); and 3) the influence of
      breathing pattern and respiratory drive on both AI and sensitivity. Sensitivities
      to detect asynchronies were low either according to experience (0.20 (95% CI 0.14
      0.29) for expert versus 0.21 (95% CI 0.12-0.30) for nonexpert, p=0.837) or
      interface (0.28 (95% CI 0.17-0.37) for mask versus 0.10 (95% CI 0.05-0.16) for
      helmet, p<0.0001). DTI inversely correlated with the AI (r2=0.67, p<0.0001).
      Breathing pattern and respiratory drive did not affect prevalence of asynchronies
      and sensitivity. Patient-ventilator asynchrony during NIV is difficult to
      recognise solely by visual inspection of ventilator waveforms.

PMID- 29204432
TI  - Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma
      exacerbation model.
AB  - Rhinovirus infections are common triggers of asthma exacerbations. Viruses can
      activate the inflammasome, resulting in processing and activation of caspase-1.
      This recruitment triggers production of interleukin (IL)-1beta and IL-18, which
      have been implicated in asthma. Elucidating the involvement of the inflammasome
      and its compartments, such as caspase-1, in asthma exacerbations is warranted.
      Gene expression of caspase-1 was measured in rhinovirus-infected primary
      bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection.
      In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice
      were challenged with house dust mite followed by exposures to the viral mimic
      poly(I:C). General lung inflammatory parameters and levels of T-helper type 2
      (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25
      were assessed. Caspase-1 expression was elevated after rhinoviral infection
      exclusively in bronchial epithelial cells from asthmatics. In a translational
      mouse model of asthma exacerbation effects of caspase-1 on airway inflammation
      and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no
      alterations of general lung inflammatory parameters, but showed markedly reduced
      eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were
      reduced at exacerbation in mice lacking caspase-1. Rhinovirus infection increases
      bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung
      Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of
      caspase-1 signalling is warranted to explore its role in asthma exacerbations.

PMID- 29204433
TI  - Adaptive servoventilation in clinical practice: beyond SERVE-HF?
AB  - Adaptive servoventilation (ASV) has proven effective at suppressing breathing
      disturbances during sleep, improving quality of life and cardiac surrogate
      parameters. Since the publication of the SERVE-HF-trial, ASV became restricted.
      The purpose of this study was to evaluate the clinical relevance of the SERVE-HF
      inclusion criteria in real life and estimate the portion of patients with these
      criteria with or without risk factors who are undergoing ASV treatment. We
      performed a retrospective study of all patients who were treated with ASV in a
      university-affiliated sleep laboratory. We reviewed the history of cardiovascular
      diseases, echocardiographic measurements of left ventricular ejection fraction
      (LVEF) and polysomnography. From 1998 to 2015, 293 patients received ASV, of
      which 255 (87.0%) had cardiovascular diseases and 118 (40.3%) had HF. Among those
      with HF, the LVEF was <=45% in 47 patients (16.0%). Only 12 patients (4.1%) had
      LVEF <30%. The SERVE-HF inclusion criteria were present in 28 (9.6%) ASV
      recipients. Of these patients, 3 died within 30-58 months of therapy, all with
      systolic HF and a LVEF <30%. In this study, only a small minority of ASV patients
      fell in the risk group. The number of fatalities did not exceed the expected
      mortality in optimally treated systolic HF patients.

PMID- 29204434
TI  - A qualitative study of patients' experiences of participating in SPACE for COPD:
      a Self-management Programme of Activity, Coping and Education.
AB  - The aim of this study was to understand experiences of participation in a
      supported self-management programme for chronic obstructive pulmonary disease
      (COPD). There is a wealth of clinical trials examining the outcomes of self
      management interventions for individuals with COPD, but current understanding
      regarding patients' perspectives of such complex interventions is limited.
      Further insight may help to tailor self-management interventions and maximise
      patient engagement. Semi-structured interviews were conducted with individuals
      participating in a self-management programme, SPACE for COPD. Interviews took
      place at 6 weeks and 6 months following the programme. Data were analysed at each
      time point using inductive thematic analysis, and subsequently re-examined
      together. 40 interviews were undertaken and four themes emerged from the
      analysis: perceptions of the programme; lifestyle changes; social support; and
      disrupting factors and barriers to maintaining routines. SPACE for COPD was
      acceptable to participants in this study. The importance of education and social
      support was emphasised at both time points studied, but there were challenges
      such as comorbidities, ill health of family members and limited maintenance of
      exercise behaviours over the longer term. Further consideration of the role of
      carers and partners may help to improve adherence to self-management programmes
      once healthcare professional support has stopped.

PMID- 29204435
TI  - Cytokine responses to two common respiratory pathogens in children are dependent
      on interleukin-1beta.
AB  - Protracted bacterial bronchitis (PBB) in young children is a common cause of
      prolonged wet cough and may be a precursor to bronchiectasis in some children.
      Although PBB and bronchiectasis are both characterised by neutrophilic airway
      inflammation and a prominent interleukin (IL)-1beta signature, the contribution
      of the IL-1beta pathway to host defence is not clear. This study aimed to compare
      systemic immune responses against common pathogens in children with PBB,
      bronchiectasis and control children and to determine the importance of the IL
      1beta pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of
      peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those
      with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations
      of IL-1beta, IL-6, interferon (IFN)-gamma and IL-10. Blocking with an IL-1
      receptor antagonist (IL-1Ra) modified the cellular response to pathogens,
      inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated
      PBMCs (in a separate PBB cohort). Inhibition of IFN-gamma production by IL-1Ra
      was observed across multiple cell types, including CD3+ T cells and CD56+ NK
      cells. Our findings highlight the extent to which IL-1beta regulates the cellular
      immune response against two common respiratory pathogens. While blocking the IL
      1beta pathway has the potential to reduce inflammation, this may come at the cost
      of protective immunity against NTHi and rhinovirus.

PMID- 29204436
TI  - In vitro and in vivo functional residual capacity comparisons between multiple
      breath nitrogen washout devices.
AB  - Functional residual capacity (FRC) accuracy is essential for deriving multiple
      breath nitrogen washout (MBNW) indices, and is the basis for device validation.
      Few studies have compared existing MBNW devices. We evaluated in vitro and in
      vivo FRC using two commercial MBNW devices, the Exhalyzer D (EM) and the EasyOne
      Pro LAB (ndd), and an in-house device (Woolcock in-house device, WIMR). FRC
      measurements were performed using a novel syringe-based lung model and in adults
      (20 healthy and nine with asthma), followed by plethysmography (FRCpleth). The
      data were analysed using device-specific software. Following the results seen
      with ndd, we also compared its standard clinical software (ndd v.2.00) with a
      recent upgrade (ndd v.2.01). WIMR and EM fulfilled formal in vitro FRC validation
      recommendations (>95% of FRC within 5% of known volume). Ndd v.2.00
      underestimated in vitro FRC by >20%. Reanalysis using ndd v.2.01 reduced this to
      11%, with 36% of measurements <=5%. In vivo differences from FRCpleth (mean+/-sd)
      were 4.4+/-13.1%, 3.3+/-11.8%, -20.6+/-11% (p<0.0001) and -10.5+/-10.9% (p=0.005)
      using WIMR, EM, ndd v.2.00 and ndd v.2.01, respectively. Direct device comparison
      highlighted important differences in measurement accuracy. FRC discrepancies
      between devices were larger in vivo, compared to in vitro results; however, the
      pattern of difference was similar. These results represent progress in ongoing
      standardisation efforts.

PMID- 29204437
TI  - Reference Values of Flexion and Supination in the Elbow Joint of a Cohort without
      Shoulder Pathologies.
AB  - Background: After surgery of the long head of the biceps tendon, the examination
      of the biceps brachii muscle function and strength is common clinical practice.
      The muscle strength is usually compared with the uninjured contralateral side or
      with a matched pair group assuming that the uninjured side can be used as an
      appropriate reference. Hypothesis/Purpose: The purpose of this study was to
      define reference values of the supination and flexion strength in the elbow joint
      and to investigate the influence of the arm positions and various anthropometric
      factors. Methods: 105 participants without any shoulder pathologies were
      enrolled. A full medical history was obtained and a physical examination was
      performed. The bilateral isometric testing included the supination torque in
      various forearm positions and elbow flexion strength with a custom engineered
      dynamometer. Multiple linear regression analysis was used to investigate the
      correlation of the strength and anthropometric factors. Results: Only age and
      gender were significant supination and flexion strength predictors of the elbow.
      Hence, it was possible to calculate a gender-specific regression line for each
      forearm position to predict the age-dependent supination torque. The supination
      strength was greatest with the arm in 90 degrees  elbow flexion and the upper arm
      in full pronation.

PMID- 29204438
TI  - Endovascular Treatment for Acute Thromboembolic Occlusion of the Superior
      Mesenteric Artery and the Outcome Comparison between Endovascular and Open
      Surgical Treatments: A Retrospective Study.
AB  - We reported our experience with endovascular treatment for patients with acute
      thromboembolic occlusion of the superior mesenteric artery (ATOS) as well as
      comparing the efficacy between endovascular and traditional open surgical
      treatments. Eighteen consecutive patients with ATOS who received endovascular
      treatment and 12 patients who received open surgical treatment between February
      2007 and October 2012 at Tianjin Union Medical Center (Tianjin, China) were
      retrospectively reviewed. Primary clinical outcomes included the technical
      success, requirement of laparotomy, length of bowel resection, perioperative
      mortality within 30 days, and surgical complications. The patients were followed
      up for 0.1 to 98 months. For patients who underwent endovascular treatment,
      complete technical success was achieved in 8 (44.4%) patients and partial success
      was achieved in the remaining 10 (55.6%) patients. Laparotomy was required in 6
      (33.3%) patients. The 30-day mortality was 16.7%. In comparison to open surgical
      therapy, endovascular therapy achieved lower requirement of laparotomy (in 33.3%
      versus in 58.3% of cases, p = 0.18), significantly shorter average length of
      bowel resection (88 +/- 44 versus 253 +/- 103 cm, p = 0.01), and lower mortality
      rate (16.7% versus 33.3%, p = 0.68). The endovascular therapy is a promising
      treatment alternative for ATOS.

PMID- 29204439
TI  - The Immunomodulatory Imbalance in Patients with Ketamine Cystitis.
AB  - The pathogenesis of ketamine cystitis (KC) has been recently linked with immune
      response to patients but the same has not yet been established. Hence, this study
      aims to propose a possible immune mechanism of irreversible bladder damage caused
      by KC. A total of 53 KC patients and 21 healthy volunteers as controls have been
      retrospectively assessed. The levels of serum immunoglobulin E (IgE), IL-6, and
      IFN-gamma of KC patients were significantly higher than those of controls,
      whereas the TGF-beta levels of KC patients substantially reduced but the IL-2 and
      IL-4 levels of KC patients were comparable to those of controls. Moreover, the KC
      patients had significantly higher counts of TH1, TH2, and TH17 cells than those
      of controls. The immune response of KC users may begin with the IL-6 production
      and differentiation of TH17 and may be followed by alternating between high
      expressions of TH1 and TH2. The IL-6 may further suppress the TREG cells which
      can aggravate chronic inflammation in KC patients and the imbalance in TH17 and
      TREG cells may involve the pathogenesis of KC. Further investigation is needed to
      define the role of IL-6 in TH1/TH2/TH17-regulated signaling pathway in ketamine
      induced cystitis.

PMID- 29204440
TI  - Functional Activation-Informed Structural Changes during Stroke Recovery: A
      Longitudinal MRI Study.
AB  - Objective: Neuroimaging studies revealed the functional reorganization or the
      structural changes during stroke recovery. However, previous studies did not
      combine the functional and structural information and the results might be
      affected by heterogeneous lesion. This study aimed to investigate functional
      activation-informed structural changes during stroke recovery. Methods: MRI data
      of twelve stroke patients were collected at four consecutive time points during
      the first 3 months after stroke onset. Functional activation during finger
      tapping task was used to inform the analysis of structural changes of activated
      brain regions. Correlation between structural changes in motor-related activated
      brain regions and motor function recovery was estimated. Results: The averaged
      gray matter volume (aGMV) of contralesional activated brain regions and
      laterality index of gray matter volume (LIGMV) increased during stroke recovery,
      and LIGMV was positively correlated with Fugl-Meyer Index (FMI) at initial stage
      after stroke. The aGMV of bilateral activated brain regions was negatively
      correlated with FMI during the stroke recovery. Conclusion: This study
      demonstrated that combining the stroke-induced functional reorganization and
      structural change provided new insights into the underlying innate plasticity
      process during stroke recovery. Significance: This study proposed a new approach
      to integrate functional and structural information for investigating the innate
      plasticity after stroke.

PMID- 29204442
TI  - In Vitro Screening of Three Indian Medicinal Plants for Their Phytochemicals,
      Anticholinesterase, Antiglucosidase, Antioxidant, and Neuroprotective Effects.
AB  - Cooccurrence of Diabetes Mellitus and Alzheimer's disease in elder people prompts
      scientists to develop multitarget agents that combat causes and symptoms of both
      diseases simultaneously. In line with this modern paradigm and as a follow-up to
      our previous studies, the present study is designed to investigate the crude
      methanolic extracts and subsequent CHCl3, n-BuOH, and H2O fractions of Acalypha
      alnifolia, Pavetta indica, and Ochna obtusata for their inhibitory activities
      towards specific targets involved in AD and DM, namely, acetylcholinesterase,
      butyrylcholinesterase, and alpha-glucosidase (alpha-Glc). The methanolic extract
      and its derived chloroform fractions exhibited remarkable inhibitory capacities
      with IC50 values being found at the MUg/mL level. Further studies on most active
      chloroform fractions presented a prominent ability to scavenge DPPH and ABTS
      reactive species and highest neuroprotective effect against H2O2 induced cell
      injury. Phytochemical analysis showed a large amount of phenolics, flavonoids,
      and terpenoids in active fractions. In conclusion, A. alnifolia, P. indica, and
      O. obtusata could be promising sources for the treatment of AD and DM since these
      fractions induced significant anticholinesterase, antidiabetic, antioxidant, and
      neuroprotection effects attributable to phenolic, flavonoid, and terpenoid
      contents and encourage further studies for development of multifunctional
      therapeutic agent for AD and DM dual therapy.

PMID- 29204441
TI  - Preemptive Analgesic and Antioxidative Effect of Curcumin for Experimental
      Migraine.
AB  - Objective: Our study aimed to investigate the analgesic and antioxidative stress
      effects of Curcumin (CC) in experimental migraine induced by Nitroglycerin (NTG)
      on rats, compared with Indomethacin (ID) and Propranolol (PP) treatments.
      Material and Methods: Five groups of 10 rats treated i.p. were investigated:
      control group (healthy rats) injected with saline solution (0.9%), NTG-control
      group injected with NTG (1 mg/100 gbw, bw = body weight), and three groups with
      pretreatment applied 30 min previous to the formalin test (NTG + CC group:
      Curcumin (10 mg/100 gbw), NTG + PP group: Propranolol (100 MUg/100 gbw), and NTG
      + ID group: Indomethacin (0.5 mg/100 gbw)). Formalin test was performed and
      number of flinches and shakes were counted. Several oxidative stress parameters
      were also assessed. Results: The smallest values of malondialdehyde (MDA), nitric
      oxide (NOx), and total oxidative status (TOS) were observed on NTG + CC with
      significant differences as compared with the control group (p < 0.0001). The
      group pretreated with Curcumin proved significantly smaller number of flinches
      and shakes compared with both NTG + PP and NTG + ID. Conclusion: Our study
      demonstrates a superior activity of Curcumin not only versus control, but also
      versus Propranolol and Indomethacin.

PMID- 29204443
TI  - Dissatisfaction in Child Welfare and Its Role in Predicting Self-Efficacy and
      Satisfaction at Work: A Mixed-Method Research.
AB  - Child welfare organizations are increasingly concerned with challenges emerging
      from the assessment of social workers' dissatisfaction. This type of service
      represents the work area where social workers are at greater risk of burnout.
      Although several studies account for high social workers' burnout scores, they do
      not systematically dwell upon its sources and roots. In addition, scholars point
      out that a considerable number of work related issues may be perceived both as a
      source of dissatisfaction and satisfaction. We assume that there is a need to
      deepen the understanding of how dissatisfaction's sources may exert an impact on
      both personal job satisfaction and professional self-efficacy, which are
      positively associated with well-being at work. The present mixed-method research
      has two aims: (1) the extensive exploration, applying qualitative methodology, of
      the perceived sources of dissatisfaction; (2) the attempt to identify the extent
      to which those sources predict job satisfaction and professional self-efficacy.
      It is our purpose to further explore which differences emerge by age. The
      research involved child welfare workers, that is, SWs employed in public child
      welfare agencies in the North East of Italy. Results show the predominant role of
      interpersonal trust and mutual respect, as main predictors of both professional
      self-efficacy and job satisfaction. Practical implications of findings are
      discussed.

PMID- 29204444
TI  - The Finite Element Simulation of the Upper Airway of Patients with Moderate and
      Severe Obstructive Sleep Apnea Hypopnea Syndrome.
AB  - Objectives: To investigate the snoring modes of patients with Obstructive Sleep
      Apnea Hypopnea Syndrome and to discover the main sources of snoring in soft
      tissue vibrations. Methods: A three-dimensional finite element model was
      developed with SolidEdge to simulate the human upper airway. The inherent modal
      simulation was conducted to obtain the frequencies and the corresponding shapes
      of the soft tissue vibrations. The respiration process was simulated with the
      fluid-solid interaction method through ANSYS. Results: The first 6 orders of
      modal vibration were 12 Hz, 18 Hz, 21 Hz, 22 Hz, 36 Hz, and 39 Hz. Frequencies of
      modes 1, 2, 4, and 5 were from tongue vibrations. Frequencies of modes 3 and 6
      were from soft palate vibrations. Steady pressure distribution and air
      distribution lines in the upper airway were shown clearly in the fluid-solid
      interaction simulation results. Conclusions: We were able to observe the
      vibrations of soft tissue and the modeled airflow by applying the finite element
      methods. Future studies could focus on improving the soft tissues vibration
      compliances by adjusting the model parameters. Additionally, more attention
      should be paid to vibrational components below 20 Hz when performing an acoustic
      analysis of human snore sounds due to the presence of these frequencies in this
      model.

PMID- 29204445
TI  - Dental Implant Surrounding Marginal Bone Level Evaluation: Platform Switching
      versus Platform Matching-One-Year Retrospective Study.
AB  - The benefits and feasibility of platform switching have been discussed in several
      studies, reporting lesser crestal bone loss in platform-switched implants than in
      platform-matched implants. Objective. The aim of the present study was to observe
      the changes in vertical and horizontal marginal bone levels in platform-switched
      and platform-matched dental implants. Materials and Methods. 51 patients received
      60 dental implants in the present study over a 1-year period. Measurement was
      performed between the implant shoulder and the most apical and horizontal
      marginal defect by periapical radiographs to examine the changes of peri-implant
      alveolar bone before and 12 months after prosthodontic restoration delivery.
      Results. These marginal bone measurements showed a bone gain of 0.23 +/- 0.58 mm
      in the vertical gap and 0.22 +/- 0.53 mm in the horizontal gap of platform
      matching, while in platform switching a bone gain of 0.93 +/- 1 mm (P < 0.05) in
      the vertical gap and 0.50 +/- 0.56 mm in the horizontal gap was found. The
      average vertical gap reduction from the baseline until 12 months was 0.92 +/-
      1.11 mm in platform switching and 0.29 +/- 0.85 mm in platform matching (P <
      0.05). Conclusions. Within the limitations of the present study, platform
      switching seemed to be more effective for a better peri-implant alveolar bone
      vertical and horizontal gap reduction at 1 year.

PMID- 29204446
TI  - miR-195-5p Suppresses the Proliferation, Migration, and Invasion of Oral Squamous
      Cell Carcinoma by Targeting TRIM14.
AB  - MicroRNAs (miRNAs) play an essential role in tumor biological processes through
      interacting with specific gene targets. The involvement of miR-195-5p in cell
      proliferation, invasion, and migration has been demonstrated in several cancer
      cell lines, while its function in oral squamous cell carcinoma (OSCC) remains
      unclear. Here we find that miR-195-5p expression is lower in OSCC than in
      nontumor tissues, while its overexpression in cell lines can lead to the
      promotion of apoptosis and the reduction of cell growth, migration, and invasion.
      Moreover, we identify the tripartite motif-containing protein (TRIM14) as a
      target of miR-195-5p. Therefore, we reason that the tumor suppressor role of miR
      195-5p in OSCC is dependent on the interaction with TRIM14.

PMID- 29204448
TI  - Punctaporonins N-S, New Caryophyllene Sesquiterpenoids from Cytospora sp.
AB  - Six new caryophyllene sesquiterpenoids, punctaporonins N-S (1-6), and three known
      ones, 6-hydroxypunctaporonins B (7), A (8), and E (9), have been isolated from
      solid cultures of Cytospora sp. The structures of 1-6 were elucidated primarily
      by NMR spectroscopy. The absolute configuration of 1 was assigned by X-ray
      crystallographic analysis of its S-MTPA ester. Compounds 2, 5, and 6 showed
      modest cytotoxicity against HeLa cells.

PMID- 29204447
TI  - Effects of LncRNA BC168687 siRNA on Diabetic Neuropathic Pain Mediated by P2X7
      Receptor on SGCs in DRG of Rats.
AB  - Diabetic neuropathic pain (DNP), one of the early symptoms of diabetic
      neuropathy, relates to metabolic disorders induced by high blood glucose,
      neurotrophic vascular ischemia and hypoxia, and autoimmune factors. This study
      was aimed at exploring the effects of long noncoding RNA (lncRNA) BC168687 siRNA
      on DNP mediated by P2X7 receptor on SGCs in DRG of rats. The mechanical
      withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, the
      expression levels of P2X7 mRNA and protein in the DRG, and nitric oxide (NO) in
      the serum were, respectively, detected in our study. Our experimental results
      showed that the level of BC168687 mRNA in DNP group was markedly higher than that
      of control group; the MWT and TWL of DNP + BC168687 si group were significantly
      increased, and the expression levels of P2X7 in DRG and the concentrations of NO
      in serum of DNP + BC168687 si group were decreased compared to those of the DNP
      group. In conclusion, lncRNA BC168687 may participate in the pathogenesis of DNP
      mediated by P2X7 receptor, which will provide a novel way for the study of the
      pathogenesis of diabetes mellitus complicated with neuropathic pain and its
      prevention and treatment.

PMID- 29204449
TI  - Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in
      Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of
      Keratinocyte.
AB  - RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the
      transcriptomic level, and many biomarkers have been discovered to be related to
      the immune response, lipid metabolism, and keratinocyte proliferation. However,
      few studies have combined analysis from various datasets. In this study, we
      integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of
      psoriasis through the analysis of differentially expressed genes (DEGs), pathway
      analysis, and functional annotation. The revealed biomarkers were further
      validated through proliferation phenotypes. The results showed that DEGs were
      functionally related to lipid metabolism and keratinocyte differentiation
      dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G
      gene families, as well as pathways that include the PPAR signaling pathway,
      cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and
      glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further
      validated the role that the AKR1B10 gene plays in proliferation. Our study
      demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing
      but also its important role in the overproliferation and migration of
      keratinocyte, which provided evidence for further therapeutic uses for psoriasis.

PMID- 29204452
TI  - Recurrent Lactobacillus Bacteremia in a Patient With Leukemia.
AB  - Lactobacillus species are a commensal flora of the human gastrointestinal and the
      female genitourinary tract. Lactobacilli especially the rhamnosus species, are
      common components of commercial probiotics. They are rarely associated with
      pathology in immunocompetent people, but they have been known to cause dental
      caries, bacteremia, and endocarditis in patients with suppressed immune function.
      Cases of Lactobacillus bacteremia have been reported in patients with acute
      myeloid leukemia, large granular lymphocytic leukemia, and in transplant
      recipients. In this article, we report a strange case of recurrent Lactobacillus
      bacteremia causing multiple episodes of fever of unknown origin in a patient with
      leukemia. This report is unique as Lactobacillus is not recognized as a common
      source of bacteremia. Moreover, the source of the bacillus continued to elude us
      even after extensive investigation.

PMID- 29204451
TI  - Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic
      Th2 Immune Responses in Mice.
AB  - Background: TLR ligands can promote Th1-biased immune responses, mimicking potent
      stimuli of viruses and bacteria. Aim: To investigate the adjuvant properties of
      dual TLR2/7 ligands compared to those of the mixture of both single ligands.
      Methods: Dual TLR2/7 ligands: CL401, CL413, and CL531, including CL264 (TLR7
      ligand) and Pam2CysK4 (TLR2-ligand), were used. Immune-modulatory capacity of the
      dual ligands with the individual ligands alone or as a mixture in mouse BMmDCs,
      BMmDC:TC cocultures, or BMCMCs was compared and assessed in naive mice and in a
      mouse model of OVA-induced intestinal allergy. Results: CL413 and CL531 induced
      BMmDC-derived IL-10 secretion, suppressed rOVA-induced IL-5 secretion from OVA
      specific DO11.10 CD4+ TCs, and induced proinflammatory cytokine secretion in
      vivo. In contrast, CL401 induced considerably less IL-10 secretion and led to IL
      17A production in BMmDC:TC cocultures, but not BMCMC IL-6 secretion, or IL-6 or
      TNF-alpha production in vivo. No immune-modulating effects were observed with
      single ligands. All dual TLR2/7 ligands suppressed DNP-induced IgE-and-Ag
      specific mast cell degranulation. Compared to vaccination with OVA, vaccination
      with the mixture CL531 and OVA, significantly suppressed OVA-specific IgE
      production in the intestinal allergy model. Conclusions: Based on beneficial
      immune-modulating properties, CL413 and CL531 may have utility as potential
      adjuvants for allergy treatment.

PMID- 29204450
TI  - The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic
      Polyneuropathy.
AB  - Diabetic polyneuropathy (DPN) is the most frequent and prevalent chronic
      complication of diabetes mellitus (DM). The state of persistent hyperglycemia
      leads to an increase in the production of cytosolic and mitochondrial reactive
      oxygen species (ROS) and favors deregulation of the antioxidant defenses that are
      capable of activating diverse metabolic pathways which trigger the presence of
      nitro-oxidative stress (NOS) and endoplasmic reticulum stress. Hyperglycemia
      provokes the appearance of micro- and macrovascular complications and favors
      oxidative damage to the macromolecules (lipids, carbohydrates, and proteins) with
      an increase in products that damage the DNA. Hyperglycemia produces mitochondrial
      dysfunction with deregulation between mitochondrial fission/fusion and regulatory
      factors. Mitochondrial fission appears early in diabetic neuropathy with the
      ability to facilitate mitochondrial fragmentation. Autophagy is a catabolic
      process induced by oxidative stress that involves the formation of vesicles by
      the lysosomes. Autophagy protects cells from diverse stress factors and routine
      deterioration. Clarification of the mechanisms involved in the appearance of
      complications in DM will facilitate the selection of specific therapeutic options
      based on the mechanisms involved in the metabolic pathways affected. Nowadays,
      the antioxidant agents consumed exogenously form an adjuvant therapeutic
      alternative in chronic degenerative metabolic diseases, such as DM.

PMID- 29204453
TI  - Physical and Functional Differences in Youth Baseball Players With and Without
      Throwing-Related Pain.
AB  - Background: Identifying risk factors that contribute to shoulder and elbow pain
      within youth baseball players is important for improving injury prevention and
      rehabilitation strategies. Hypothesis: Differences will exist between youth
      baseball players with and without a history of upper extremity pain on measures
      related to growth, shoulder performance, and baseball exposure. Study Design:
      Case-control study; Level of evidence, 3. Methods: A total of 84 youth baseball
      players were divided into 2 groups based on self-reported history of throwing
      related arm pain. Group differences for growth-related, shoulder performance, and
      baseball exposure variables were analyzed by use of parametric and nonparametric
      tests, as appropriate. Multivariate logistic regression was used to assess
      variables most predictive of pain. Results: The group of athletes with pain (n =
      16) were taller and heavier, played more baseball per year, and had greater
      pitching velocity. Athletes with pain also had greater loss of internal rotation
      range of motion and greater side-to-side asymmetry in humeral retrotorsion (HRT),
      attributable to lower degrees of HRT within the nondominant humerus. Multivariate
      analysis revealed that player height was most predictive of pain, with a 1-inch
      increase in height resulting in a 77% increased risk of pain. Conclusion:
      Vertical growth that accompanies adolescence increases the risk of experiencing
      throwing-related pain in youth baseball players. Players who are taller,
      particularly those with faster pitching velocities, are at the greatest risk for
      developing pain and should be more carefully monitored for resultant injury. The
      degree of nondominant HRT may have a relationship to the development of pain, but
      further research is required to better understand the implications of this
      observation.

PMID- 29204454
TI  - Magnetic Resonance Imaging for Patellofemoral Chondromalacia: Is There a Role for
      T2 Mapping?
AB  - Background: Patellofemoral pain is common, and treatment is guided by the
      presence and grade of chondromalacia. Purpose: To evaluate and compare the
      sensitivity and specificity in detecting and grading chondral abnormalities of
      the patella between proton density fat suppression (PDFS) and T2 mapping magnetic
      resonance imaging (MRI). Study Design: Cohort study; Level of evidence, 2.
      Methods: A total of 25 patients who underwent MRI of the knee with both a PDFS
      sequence and T2 mapping and subsequently underwent arthroscopic knee surgery were
      included. The cartilage surface of the patella was graded on both MRI sequences
      by 2 independent, blinded radiologists. Cartilage was then graded during
      arthroscopic surgery by a sports medicine fellowship-trained orthopaedic surgeon.
      Reliability, sensitivity, specificity, and accuracy were determined for both MRI
      methods. The findings during arthroscopic surgery were considered the gold
      standard. Results: Intraobserver and interobserver agreement for both PDFS (98.5%
      and 89.4%, respectively) and T2 mapping (99.4% and 91.3%, respectively) MRI were
      excellent. For T2 mapping, the sensitivity (61%) and specificity (64%) were
      comparable, whereas for PDFS there was a lower sensitivity (37%) but higher
      specificity (81%) in identifying cartilage abnormalities. This resulted in a
      similar accuracy for PDFS (59%) and T2 mapping (62%). Conclusion: Both PDFS and
      T2 mapping MRI were reliable but only moderately accurate in predicting patellar
      chondromalacia found during knee arthroscopic surgery.

PMID- 29204456
TI  - Erratum: Publisher's Note: "Enzyme transient state kinetics in crystal and
      solution from the perspective of a time-resolved crystallographer" [Struct. Dyn.
      1, 024701 (2014)].
AB  - [This corrects the article DOI: 10.1063/1.4869472.].

PMID- 29204455
TI  - A null model for cortical representations with grandmothers galore.
AB  - There has been extensive discussion in the literature about the extent to which
      cortical representations can be described as localist or distributed. Here we
      discuss a simple null model that encompasses a family of related architectures
      describing the transformation of signals throughout the parts of the visual
      system involved in object recognition. This family of models constitutes a
      rigorous first approximation to explain the neurophysiological properties of
      ventral visual cortex. This null model contains both distributed and local
      representations throughout the entire hierarchy of computations and the responses
      of individual units are meaningful and interpretable when encoding is adequately
      defined for each computational stage.

PMID- 29204457
TI  - Employing a Qualitative Description Approach in Health Care Research.
AB  - A qualitative description design is particularly relevant where information is
      required directly from those experiencing the phenomenon under investigation and
      where time and resources are limited. Nurses and midwives often have clinical
      questions suitable to a qualitative approach but little time to develop an
      exhaustive comprehension of qualitative methodological approaches. Qualitative
      description research is sometimes considered a less sophisticated approach for
      epistemological reasons. Another challenge when considering qualitative
      description design is differentiating qualitative description from other
      qualitative approaches. This article provides a systematic and robust journey
      through the philosophical, ontological, and epistemological perspectives, which
      evidences the purpose of qualitative description research. Methods and rigor
      issues underpinning qualitative description research are also appraised to
      provide the researcher with a systematic approach to conduct research utilizing
      this approach. The key attributes and value of qualitative description research
      in the health care professions will be highlighted with the aim of extending its
      usage.

PMID- 29204458
TI  - Etonogestrel Implant-To Leave or Stay: A Case Series.
AB  - Long-acting reversible contraception, which include etonogestrel subdermal
      hormonal implants, has high efficiency rates in preventing teen pregnancy.
      Although these numbers are increasing, teens have the lowest long-acting
      reversible contraception usage rate of any group, which the American Congress of
      Obstetricians and Gynecologists addressed with recommendations for Nexplanon
      placement for teens. The American Congress of Obstetricians and Gynecologists has
      recommended support for increased use and training of practitioners and
      pediatricians to gain momentum. Safety remains a concern as increased usage by
      practitioners and pediatricians may lead to more adverse outcomes. Despite the
      improvements to Nexplanon as a preloaded insertion device to prevent deep
      placement and malalignment, there are few known published adverse outcomes.
      Although different products, a review of the adverse outcomes reported with
      Norplant removal may closely reflect today's concerns with Nexplanon. The 3 case
      studies in this article are examples of similar adverse outcome with Nexplanon
      removal as those reported with Norplant.

PMID- 29204459
TI  - Hypertension in Low-Income Adolescents.
AB  - Disadvantaged adolescents are at higher risk for undiagnosed and untreated
      obesity and hypertension. Using nurse-measured weight, height, and blood pressure
      (BP) as well as self-reported age and activity/lifestyle behaviors, we assessed
      the prevalence of obesity and hypertension in 573 adolescent patients aged 13.0
      to 17.9 years (females: n = 267, 46.6%; males: n = 306, 53.4%) from a clinic
      serving low-income, ethnically diverse pediatric patients. Body mass index
      distribution was as follows: 11, underweight (1.9%); 330, healthy weight (57.6%);
      105, overweight (18.3%); and 127, obese (22.2%). The age-adjusted height
      percentile was normally distributed, but distribution by BP category was 326
      normotensive (56.9%), 147 prehypertensive (25.7%), 60 with stage 1 hypertension
      (10.5%), and 40 with stage 2 hypertension (7.0%). Activity and lifestyle
      behaviors did not adequately explain obesity and hypertension rates. Efforts to
      prevent/reduce childhood overweight, obesity, and hypertension in underserved
      populations need to include dietary education, weight control interventions, and
      physical activity programs specifically tailored to overweight/obese youth and
      parents.

PMID- 29204460
TI  - A Cardiac Mass in a Neonate.

PMID- 29204461
TI  - The Association Between BXO and Obesity in Boys Undergoing Circumcision.
AB  - This study investigated whether boys with balanitis xerotica obliterans (BXO)
      have increased rates of obesity compared with boys with no concern for BXO (NCB).
      Boys <=18 years old with circumcision pathology-confirmed BXO were compared with
      an age-matched group who had NCB during circumcision. Boys with BXO were found to
      have a mean body mass index of 70.64 percentile for age compared with 52.43
      percentile in age-matched controls (P = .0005). The rate of obesity was
      significantly higher in boys with BXO (42%) compared with 12.4% in boys with NCB
      (odds ratio = 5.12; 95% CI = 2.6 to 10.06). Given the increasing rates of
      childhood obesity and the long-term health consequences of both BXO and obesity,
      special attention should be paid to this population. Further research is needed
      to determine if BXO in obese children may represent an early indicator of a
      systemic disease process where intervention may be warranted.

PMID- 29204462
TI  - Human Papillomavirus Vaccine Sources of Information and Adolescents' Knowledge
      and Perceptions.
AB  - Understanding where adolescents obtain information about human papillomavirus
      (HPV) vaccines may be helpful in designing public health interventions promoting
      HPV vaccination. This study assessed the following: (1) exposure to specific
      sources of information about HPV vaccines, (2) self-reported helpfulness of these
      sources of information, and (3) whether the specific source of information was
      associated with knowledge and perceptions about HPV vaccines among adolescent
      girls. There were 339 adolescent girls (mean age = 16.8 years) recruited into the
      study. Television advertisements, the Internet, doctors/nurses, and mothers were
      the most frequently reported sources of vaccine information; more than 90% of
      participants who received information from these sources reported they were
      helpful. Adolescents who received information about HPV vaccines from television
      advertisements, the Internet, clinicians, and mothers had higher knowledge about
      HPV vaccines and more positive perceptions. Assuring the accuracy of messages
      from these sources will be essential, given their importance in influencing
      adolescents' knowledge and perceptions about HPV vaccines.

PMID- 29204463
TI  - Effect of Flavors and Modified Risk Messages on E-cigarette Abuse Liability.
AB  - Objectives: To measure e-cigarettes' abuse liability compared to conventional
      tobacco cigarettes under flavor and message conditions amenable to regulation.
      Methods: Two studies used 2*2 within-subjects designs with factors of e-cigarette
      flavor (Study 1: tobacco vs. menthol; Study 2: cherry vs. unflavored) and message
      (Study 1: reduced harm vs. no message; Study 2: reduced exposure to carcinogens
      vs. no message) with cigarette smokers (N(total) = 36). Linear mixed effects
      models assessed abuse liability for tobacco products. Outcomes included the price
      after which consumption is zero (the maximum amount participants would pay for a
      tobacco product) from the multiple choice procedure (MCP) and cigarette purchase
      task (CPT) and demand elasticity (price sensitivity) from the CPT. Results: In
      the MCP, the price where consumption reached zero was significantly lower in all
      e-cigarette conditions except tobacco flavor (message or no message) compared to
      cigarettes (p < .05 each). Demand elasticity was significantly higher for
      menthol/no message and unflavored/reduced exposure message conditions relative to
      cigarettes (p < .05 each). Conclusions: Flavors and modified risk messages
      included with e-cigarettes may affect e-cigarette abuse liability among smokers,
      suggesting regulatory pathways to influence demand for conventional and
      alternative tobacco products.

PMID- 29204465
TI  - Non-contributory social transfer programs in developing countries: A new dataset
      and research agenda.
AB  - Social transfer programs in developing countries are designed to contribute to
      poverty reduction by increasing the income of the poor in order to ensure minimal
      living standards. In addition, social transfers provide a safety net for the
      vulnerable, who are typically not covered by contributory social security. The
      question of how effective such programs are in achieving these aims has been the
      subject of numerous impact evaluations. However, the optimal design of such
      programs is still unclear. Even less is known about whether the adoption and
      implementation of transfer programs is really driven by poverty and neediness or
      whether other factors also have an influence. To investigate these and other
      research questions, we have developed a new dataset entitled Non-Contributory
      Social Transfer Programs (NSTP) in Developing Countries. One advantage of this
      dataset is that it traces 186 non-contributory programs from 101 countries back
      in time and presents them in panel form for the period up until 2015. The second
      advantage is that it contains all the details regarding the various programs'
      designs as well as information on costs and coverage in a coded format and thus
      facilitates both comparative quantitative and in-depth qualitative analyses.
      While describing the data we discuss a number of examples of how the dataset can
      be used to explore different issues related to social policies in developing
      countries. We present suggestive evidence that the adoption of social transfer
      programs is not based only on pro-poor motives, but rather that social policy
      choices differ between political regimes.

PMID- 29204464
TI  - A multimodal dataset for authoring and editing multimedia content: The MAMEM
      project.
AB  - We present a dataset that combines multimodal biosignals and eye tracking
      information gathered under a human-computer interaction framework. The dataset
      was developed in the vein of the MAMEM project that aims to endow people with
      motor disabilities with the ability to edit and author multimedia content through
      mental commands and gaze activity. The dataset includes EEG, eye-tracking, and
      physiological (GSR and Heart rate) signals collected from 34 individuals (18 able
      bodied and 16 motor-impaired). Data were collected during the interaction with
      specifically designed interface for web browsing and multimedia content
      manipulation and during imaginary movement tasks. The presented dataset will
      contribute towards the development and evaluation of modern human-computer
      interaction systems that would foster the integration of people with severe motor
      impairments back into society.

PMID- 29204466
TI  - Restoration of anatomical continuity after spinal cord transection depends on
      Wnt/beta-catenin signaling in larval zebrafish.
AB  - This data article contains descriptive and experimental data on spinal cord
      regeneration in larval zebrafish and its dependence on Wnt/beta-catenin
      signaling. Analyzing spread of intraspinally injected fluorescent dextran showed
      that anatomical continuity is rapidly restored after complete spinal cord
      transection. Pharmacological interference with Wnt/beta-catenin signaling (IWR-1)
      impaired restoration of spinal continuity. For further details and experimental
      findings please refer to the research article by Wehner et al. Wnt signaling
      controls pro-regenerative Collagen XII in functional spinal cord regeneration in
      zebrafish (Wehner et al., 2017) [1].

PMID- 29204467
TI  - Home energy management (HEM) database: A list with coded attributes of 308
      devices commercially available in the US.
AB  - Policymakers worldwide are currently discussing whether to include home energy
      management (HEM) products in their portfolio of technologies to reduce carbon
      emissions and improve grid reliability. However, very little data is available
      about these products. Here we present the results of an extensive review
      including 308 HEM products available on the US market in 2015-2016. We gathered
      these data from publicly available sources such as vendor websites, online
      marketplaces and other vendor documents. A coding guide was developed iteratively
      during the data collection and utilized to classify the devices. Each product was
      coded based on 96 distinct attributes, grouped into 11 categories: Identifying
      information, Product components, Hardware, Communication, Software, Information -
      feedback, Information - feedforward, Control, Utility interaction, Additional
      benefits and Usability. The codes describe product features and functionalities,
      user interaction and interoperability with other devices. A mix of binary
      attributes and more descriptive codes allow to sort and group data without losing
      important qualitative information. The information is stored in a large
      spreadsheet included with this article, along with an explanatory coding guide.
      This dataset is analyzed and described in a research article entitled "Categories
      and functionality of smart home technology for energy management" (Ford et al.,
      2017) [1].

PMID- 29204468
TI  - Dataset of quantitative spectral EEG of different stages of kindling acquisition
      in rats.
AB  - The data represented here are in relation with the manuscript "Quantitative
      assessments of extracellular EEG to classify specific features of main phases of
      seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017) [1]
      which quantitatively classified different main stages of the kindling process
      based on their electrophysiological characteristics using EEG signal processing.
      The data in the graphical form reported the contribution of different sub bands
      of EEG in different stages of kindling- induced epileptogenesis. Only EEG signals
      related to stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage
      (LSS)), and 4-5 (generalized seizure stages (GSSs) were transferred into
      frequency function by Fast Fourier Transform (FFT) and their power spectrum and
      power of each sub bands including delta (1-4 Hz), Theta (4-8 Hz), alpha (8-12
      Hz), beta (12-28 Hz), gamma (28-40 Hz) were calculated with MATLAB 2013b.
      Accordingly, all results were obtained quantitatively which can contribute to
      reduce the errors in the behavioral assessments.

PMID- 29204469
TI  - High-frequency electrical stimulation (HFES) Data Lean and Obese Zucker Rat
      Soleus Muscle: Regulation of p70S6kinase Associated Proteins.
AB  - Anaerobic exercise has been advocated as a prescribed treatment for the
      management of diabetes: however, alterations in exercise-induced signaling remain
      largely unexplored in the diabetic muscle. Here, we compare the basal and the in
      situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K,
      Pten, and Shp2 proteins in the lean and obese (fa/fa) Zucker rat soleus muscle
      following a single bout of contractile stimuli. This article represents data
      associated with prior publications from our lab (Katta et al., 2009a, 2009b;
      Tullgren et al., 1991) [1-3] and concurrent Data in Brief articles (Ginjupalli et
      al., 2017a, 2017b; Rice et al., 2017a, 2017b) [4-7].

PMID- 29204470
TI  - Survey data on cost and benefits of climate smart agricultural technologies in
      western Kenya.
AB  - This paper describes data that were collected in three counties of western Kenya,
      namely Siaya, Bungoma, and Kakamega. The main aim of collecting the data was to
      assess the climate smartness, profitability and returns of soil protection and
      rehabilitation measures. The data were collected from 88 households. The
      households were selected using simple random sampling technique from a primary
      sampling frame of 180 farm households provided by the ministry of agriculture
      through the counties agricultural officers. The surveys were administered by
      trained research assistants using a structured questionnaire that was designed in
      Census and Survey Processing System (CSPro). Later, the data was exported to
      STATA version 14.1 for cleaning and management purposes. The data are hosted in
      an open source dataverse to allow other researchers generate new insights from
      the data (http://dx.doi.org/10.7910/DVN/K6JQXC).

PMID- 29204471
TI  - Data on the involvement of Meox1 in balloon-injury-induced neointima formation of
      rats.
AB  - In the previous report, Meox1 was found to promote SMCs phenotypic modulation and
      injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy
      signaling cascade (Wu et al., 2017) [1]. Here, we presented new original data on
      the involvement of Mesoderm/mesenchyme homeobox gene l (Meox1) in balloon-injury
      induced neointima formation of rat. In rat carotid artery balloon injury model to
      induce vascular remodeling, Meox1 was induced in vascular smooth muscle cell
      (SMCs) of rat carotid arteries. Most proliferating cell nuclear antigen (PCNA)
      positive cells also expressed Meox1. These data suggested that Meox1 may be
      involved in SMCs proliferation during injury-induced neointima formation.
      Furthermore, knocked down its expression in injured arteries by adenoviral
      delivery of Meox1 short hairpin RNA (shRNA) (shMeox1), neointima formation was
      significantly inhibited. Elastin staining also confirmed the reduction of
      neointima in Meox1 shRNA-transduced arteries. Moreover, knockdown of Meox1
      decreased the collagen production/deposition that was significantly increased in
      neointima induced by balloon injury.

PMID- 29204472
TI  - Data on pollutants content in the influent and effluent from wastewater treatment
      plant of Rasht in Guilan Province, Iran.
AB  - Data on this paper show the concentrations of COD, BOD5, TSS, K+, Ca2+, Na+, Cl-,
      [Formula: see text], [Formula: see text], Mn2+, Fe2+, Mg2+, Zn2+, Ni, Pb, Cu and
      Cd in the influent and effluent of wastewater, and also the nematode eggs, total
      and fecal coliform in effluents from wastewater treatment plant of Rasht, Guilan
      Province, in Iran. Measurements of pollutants in influent and effluent was
      measured according to standard methods (W.E. Federation and Association, A. P.
      H., 2005) [1]. Statistical analysis of the data was carried out using Special
      Package for Social Sciences (SPSS 16).

PMID- 29204473
TI  - Grafting C8-C16 alkyl groups altered the self-assembly and curcumin -loading
      properties of sodium caseinate in water.
AB  - The data presented here are related to the research article entitled "Synthesis
      and characterization of alkylated caseinate, and its structure-curcumin loading
      property relationship in water" (Zhang et al., 2018) [1]. This data article
      reports the detailed spectra information for 1H NMR, 13C NMR and UPLC-Q-TOF MS of
      the N-succinimidyl fatty acid esters with various alkyl chain lengths (Cn-NHSs, n
      = 8, 12, 14 and 16). 1H NMR, 13C NMR and UPLC-Q-TOF MS spectra for C16-NHS are
      shown as an example. Then the stacked 1H NMR spectra of the obtained alkylated
      caseinates (Cn-caseinates, n = 8, 12, 14 and 16) are provided. The surface
      hydrophobicity index (S0) of Cn-caseinates with different substitution degrees
      (SD) of alkyl groups is shown. Additionally, Visual appearances for the formed
      aqueous dispersions of curcumin-loaded native caseinate (NaCas) and Cn-caseinates
      self-assemblies are shown. X-ray diffraction patterns of curcumin, C16-caseinate,
      its physical mixture and curcumin-loaded C16-caseinate self-assemblies are
      examined. The re-dispersibility and short-term storage stability of the curcumin
      loaded NaCas and C16-caseinate self-assemblies are also studied.

PMID- 29204474
TI  - Data analysis on physical and mechanical properties of cassava pellets.
AB  - In this data article, laboratory experimental investigation results carried out
      at National Centre for Agricultural Mechanization (NCAM) on moisture content,
      machine speed, die diameter of the rig, and the outputs (hardness, durability,
      bulk density, and unit density of the pellets) at different levels of cassava
      pellets were observed. Analysis of variance using randomized complete block
      design with factorial was used to perform analysis for each of the outputs:
      hardness, durability, bulk density, and unit density of the pellets. A clear
      description on each of these outputs was considered separately using tables and
      figures. It was observed that for all the output with the exception of unit
      density, their main factor effects as well as two and three ways interactions is
      significant at 5% level. This means that the hardness, bulk density and
      durability of cassava pellets respectively depend on the moisture content of the
      cassava dough, the machine speed, the die diameter of the extrusion rig and the
      combinations of these factors in pairs as well as the three altogether. Higher
      machine speeds produced more quality pellets at lower die diameters while lower
      machine speed is recommended for higher die diameter. Also the unit density
      depends on die diameter and the three-way interaction only. Unit density of
      cassava pellets is neither affected by machine parameters nor moisture content of
      the cassava dough. Moisture content of cassava dough, speed of the machine and
      die diameter of the extrusion rig are significant factors to be considered in
      pelletizing cassava to produce pellets. Increase in moisture content of cassava
      dough increase the quality of cassava pellets.

PMID- 29204475
TI  - Microarray analysis of subcutaneous adipose tissue from mature cows with
      divergent body weight gain after feed restriction and realimentation.
AB  - Body weight response to periods of feed restriction and realimentation is
      critical and relevant to the agricultural industry. The purpose of this study was
      to evaluate differentially expressed genes identified in subcutaneous adipose
      tissue collected from cows divergent in body weight (BW) gain after feed
      restriction and realimentation. We compared adipose samples from cows with
      greater gain based on average daily gain (ADG) during realimentation with samples
      from cows with lesser gain. Specifically, there were four comparisons including
      two comparing the high and low gain animals across each feeding period (feed
      restriction and realimentation) and two that compared differences in feed
      restriction and realimentation across high or low gain classifications. Using
      microarray analysis, we provide a set of differentially expressed genes
      identified between the high and low gain at both periods of nutrient restriction
      and realimentation. These data identify multiple differentially expressed genes
      between these two phenotypes across both nutritional environments.

PMID- 29204476
TI  - Data documenting the performance of the PT/INR line correction method for
      reconciling INR discrepancies between central laboratory coagulation analyzers
      using different thromboplastins during the evaluation of a portable Coagulometer.
AB  - The data presented here was produced as part of an evaluation of the performance
      of the CoaguChek XS point-of-care coagulation analyzer, which is discussed in the
      research article "POCT PT INR - Is it adequate for Patient Care? A Comparison of
      the Roche Coaguchek XS vs. Stago Star vs. Siemens BCS in Patients Routinely Seen
      in an Anticoagulation Clinic" (Baker et al., in press) [1]. An effort to
      reconcile discrepancies in the patient INR result distributions from different
      central lab instruments (Stago Star and Siemens BCS) with the PT/INR line method
      is described (Poller et al., 2010, 2011; Ibrahim et al., 2011) [2], [3], [4].
      While regression analysis of the ECAA Poller calibrant data provided a linear
      PT/INR line for all methods, Pearson's chi-squared and one-way repeated measures
      ANOVA analyses showed that central lab INR measurements continued to exhibit
      measurement site dependence after the PT/INR line correction was applied.
      According to paired t-test analysis, only the human thromboplastin dependent
      methods (CoaguChek XS and Siemens BCS both before and after PT/INR line
      correction) showed statistically significant agreement (p-value >0.05).

PMID- 29204477
TI  - Data for the physical and mechanical properties of high volume fly ash cement
      paste composites.
AB  - The data presented herein are compiled of the research summary of
      "Characterization of High-Volume Fly-Ash Cement Paste for Sustainable
      Construction Application" (Aydin and Arel, 2017) [1]. This data article provides
      general information about the ASTM Class C and Class F fly ash cement paste
      composites composed of silica fume, lime, water reducing admixtures in three
      different level of workability (0 mm, 100 mm and 200 mm). The dataset here also
      helps the readers to understand the links with the basic properties of the
      ingredients, for example, how can porosity be predicted based on the mixture
      design? how can the strength of the material be linked with the basic strengths
      of the constituent ingredients?.

PMID- 29204478
TI  - Data of furfural adsorption on nano zero valent iron (NZVI) synthesized from
      Nettle extract.
AB  - Among various water and wastewater treatment methods, adsorption techniques are
      widely used to remove certain classes of pollutants due to its unique features.
      Thus, the aim of this data article is to synthesize zero valent iron
      nanoparticles (NZVI) from Nettle leaf extract by green synthesis method as an
      environmentally friendly technique, and to evaluate it's efficiency in the
      removal of furfural from aqueous solutions. The data of possible adsorption
      mechanism and isotherm of furfural on the synthesized adsorbent are depicted in
      this data article. The data acquired showed that the adsorption trend follows the
      pseudo-second order kinetic model and that the Langmuir isotherm was suitable for
      correlation of equilibrium data with the maximum adsorption capacity of 454.4
      mg/g. The information of initial furfural concentration, pH, adsorbent dosage and
      contact time effects on the removal efficiency are presented. Considering the
      findings data, the developed nanoparticle from Nettle leaf extract, as a low cost
      adsorbent, could be considered as promising adsorbent for furfural and probably
      similar organic pollutants removal from aqueous solutions.

PMID- 29204479
TI  - Note from the Editor.

PMID- 29204480
TI  - Update regarding opportunities for orthopaedic surgeons to contribute to
      postmarket surveillance of potential safety issues for orthopaedic medical
      devices marketed in the United States.

PMID- 29204481
TI  - Corrosion and adverse tissue reaction after modular unipolar hip
      hemiarthroplasty.
AB  - Modern unipolar hip hemiarthroplasty, commonly used for displaced femoral neck
      fracture, is now modular, with both a variable length cobalt-chromium adapter
      sleeve and large femoral head. Patients with these modular components may develop
      symptomatic trunnion corrosion, with elevated serum metal levels. We report the
      case of an 82-year-old woman, 5.5 years after a modular unipolar hip
      hemiarthroplasty, who presented with a 4-month history of hip pain and limp.
      Evaluation showed elevated serum cobalt and chromium levels and an acetabular
      cyst. At revision, fluid, tissue, and gross inspection were consistent with
      trunnion corrosion. The hip was revised with a ceramic head and dual mobility
      acetabular component, with a good result at 1 year. The designs of commercially
      available, modern unipolar hip hemiarthroplasty prostheses are reviewed.

PMID- 29204482
TI  - Corrosion and adverse local tissue reaction after total hip arthroplasty with a
      modular titanium alloy femoral neck.
AB  - This report describes a case of mechanically assisted crevice corrosion and
      secondary adverse local tissue reaction in a patient following a total hip
      arthroplasty, utilizing a modular neck (bi-modular) femoral component.
      Radiographic evaluation demonstrated a well-positioned, stable, cementless
      arthroplasty. Upon further evaluation, the patient had elevated serum cobalt and
      chromium levels, and magnetic resonance imaging demonstrated a periprosthetic
      pseudotumor. Corrosion of both the neck-stem and head-neck junctions was
      suspected. At the time of surgery, the neck-body junction was pristine; however,
      the head-neck junction of the implant demonstrated severe corrosive wear, a
      problem that has been reported only once previously with this particular bi
      modular implant. This serves as a reminder that any modular junction may be
      susceptible to corrosion and not all bi-modular designs behave similarly.

PMID- 29204483
TI  - Bead debonding from a modern cementless total hip femoral component with
      concomitant taper corrosion.
AB  - We report a case of bead shedding from a cylindrical extensively porous-coated
      cementless femoral component with concomitant taper corrosion at the modular head
      neck junction of a metal-on-polyethylene total hip prosthesis. The patient
      presented with chronic thigh pain 4 years after primary total hip arthroplasty,
      and radiographs revealed significant osteolysis and metallic debris around the
      femoral stem. Intraoperatively, the patient had a grossly loose femoral component
      with debonding of sintered beads from the femoral stem, as well as evidence of
      taper corrosion. We identify a failure of a modern beaded femoral component in
      conjunction with taper corrosion.

PMID- 29204484
TI  - Pseudotumor in ceramic-on-metal total hip arthroplasty.
AB  - The increasing demand for total hip arthroplasty (THA) in relatively young, high
      demand patients has led to the use of hard-on-hard bearing surfaces. Adverse
      local tissue reaction/pseudotumor and elevated serum metal ion levels are
      commonly reported complications encountered in metal-on-metal THA, while audible
      articulation and rim fracture are reported in ceramic-on-ceramic THA. For this
      reason, ceramic-on-metal THA was implemented as an ideal hard-on-hard bearing
      combination. In this report, we describe a case of bilateral simultaneous ceramic
      on-metal THA in a 69-year-old woman who presented 7 years postoperatively with
      unilateral hip pain associated with underlying pseudotumor and elevated serum
      cobalt and chromium ion levels. Pre-revision workup, intraoperative findings, and
      postoperative evaluation are included and suggest acetabular malposition as a
      potential source for complication.

PMID- 29204485
TI  - Arthroprosthetic cobaltism associated with cardiomyopathy.
AB  - Systemic cobaltism related to metal-on-metal total hip arthroplasty has been
      published in case reports and series with effects on the cardiac, neurologic,
      endocrine, and immunologic systems. This case report presents a 46-year-old male
      who underwent bilateral metal-on-metal total hip arthroplasty and subsequently
      developed cardiomyopathy requiring left ventricular assist device implantation.
      Intervention with bilateral revision to non-cobalt-containing implants resulted
      in improved cardiac function. This case report will alert clinicians to the
      presentation of this rare but devastating complication while also displaying
      improvement following revision total hip arthroplasty. It is our hope this case
      will aid in early recognition and intervention of this condition.

PMID- 29204486
TI  - Fracture of the femoral adapter bolt and taper adapter in a modern rotating
      platform knee arthroplasty.
AB  - A 58-year-old woman presented with onset of pain associated with a popping sound
      after a twisting motion 4 years after left total knee revision arthroplasty. She
      had a complex medical history, including a reported bone cement allergy, and
      presented to the hospital unable to bear weight. Plain radiographs revealed a
      broken femoral component, with the femoral metaphyseal sleeve separated from the
      distal articular component. During surgery, it was observed that the femoral
      adapter bolt and taper adapter had both fractured. Scanning electron microscopy
      of the fracture surfaces of the components confirmed that the implant had failed
      in fatigue, presumably due to high cyclic loads. Failure at this junction has not
      been described previously. In this type of knee design, we recommend supporting
      the distal articular component either with bone, augmentation, and/or bone cement
      to reduce the risk for this mode of failure.

PMID- 29204488
TI  - False-negative synovial alpha-defensin.
AB  - We present a case of chronic periprosthetic hip infection diagnosed using the
      Musculoskeletal Infection Society criteria as the gold standard. The alpha
      defensin test was falsely negative. The diagnostic workup of the patient is
      detailed, along with a discussion regarding the potential reasons behind the
      misleading alpha-defensin results. To our knowledge, this is the first reported
      case of a false-negative alpha-defensin test in the setting of an open sinus
      tract communicating with a culture-positive total hip implant. The alpha-defensin
      test should be interpreted cautiously, along with all relevant pertinent clinical
      data. In certain cases, similar to those described here, the Musculoskeletal
      Infection Society criteria may perform better than this particular biomarker.

PMID- 29204487
TI  - Fatigue fracture of a cemented Omnifit CoCr femoral stem: implant and failure
      analysis.
AB  - A cemented, cast CoCr alloy, Omnifit Plus femoral stem was retrieved following
      mid-stem fracture after 24 years in vivo. The patient was an active 55-year-old
      male with a high body mass index (31.3) and no traumatic incidents before stem
      fracture. Fractographic and fatigue-based failure analyses were performed to
      illuminate the etiology of fracture and retrospectively predict the device
      lifetime. The fracture surfaces show evidence of a coarse grain microstructure,
      intergranular fracture, and regions of porosity. The failure analysis suggests
      that stems with similar metallurgical characteristics, biomechanical
      environments, and in vivo durations may be abutting their functioning lifetimes,
      raising the possibility of an increased revision burden.

PMID- 29204489
TI  - The cyclops lesion after bicruciate-retaining total knee replacement.
AB  - The cyclops lesion is a localized anterior arthrofibrosis most commonly seen
      following anterior cruciate ligament reconstruction. The lesion forms at the
      anterior cruciate ligament insertion creating a painful extension block between
      femoral intercondylar notch and tibial plateau. We present 2 cases (3 knees) in
      which cyclops lesions appeared atypically following bicruciate-retaining total
      knee replacement. Two lesions occurred in a single patient following bilateral
      knee replacement. One lesion occurred in an active sportswoman. All 3 resolved
      following arthroscopic debridement. We describe the presentation of this unusual
      complication and suggest keys to its diagnosis, treatment, and prevention.

PMID- 29204490
TI  - Lumbar chance fracture after direct anterior total hip arthroplasty.
AB  - This report describes a patient with ankylosing spondylitis (AS) who underwent
      total hip arthroplasty (THA) by the direct anterior approach and sustained a L4-5
      extension fracture dislocation with neural deficits. A magnetic resonance imaging
      revealed an epidural hematoma at the site of the fracture causing critical
      stenosis. The patient was taken to the operating room for a L3-S1 posterior
      decompression with L2-pelvis posterior spinal fusion. AS and diffuse idiopathic
      skeletal hyperostosis create a stiff spine that predisposes to fractures because
      of the larger moment arms experienced than normal spines. The arthroplasty
      surgeon performing THA should be aware and take precautions to reduce stress on
      the spine.

PMID- 29204491
TI  - A simple technique to remove well-fixed acetabular components in revision of
      total hip arthroplasty.
AB  - Removing well-fixed acetabular components can be a challenge for orthopaedic
      surgeons in revision of total hip arthroplasty. Acetabular bone loss, fracture,
      and other complications occurred in extracting implants may result in instability
      and fail of revision. Thus, instruments are developed to avoid such
      complications. We report a simple technique by drilling a tunnel on the
      superolateral quadrant of acetabulum and using an offset staff to remove
      acetabular components without many matching units. The procedure of removing well
      fixed acetabular components is a simple, efficient, inexpensive, bone stock
      preserving technique.

PMID- 29204492
TI  - Joint replacement surgery in homeless veterans.
AB  - Total joint arthroplasty (TJA) in a homeless patient is generally considered
      contraindicated. Here, we report our known medical and social (housing and
      employment) results of homeless veterans who had TJA. Thirty-seven TJAs were
      performed on 33 homeless patients (31 men) at our hospital between November 2000
      and March 2014. This was 1.2% of all TJAs. Average age was 54 years. Average
      hospital stay was 4.1 days. There were no major inpatient complications. Thirty
      four cases had at least 1-year follow-up in any clinic within the Veterans
      Affairs health care system. There were no known surgery-related reoperations or
      readmissions. At final follow-up, 24 patients had stable housing and 9 were
      employed. The extensive and coordinated medical and social services that were
      provided to veterans from the Department of Veterans Affairs contributed to our
      positive results.

PMID- 29204493
TI  - Comparison of adverse events rates and hospital cost between customized
      individually made implants and standard off-the-shelf implants for total knee
      arthroplasty.
AB  - Background: This study compares selected hospital outcomes between patients
      undergoing total knee arthroplasty (TKA) using either a customized individually
      made (CIM) implant or a standard off-the-shelf (OTS) implant. Methods: A
      retrospective review was conducted on 248 consecutive TKA patients treated in a
      single institution, by the same surgeon. Patients received either CIM (126) or
      OTS (122) implants. Study data were collected from patients' medical record or
      the hospital's administrative billing record. Standard statistical methods tested
      for differences in selected outcome measures between the 2 study arms. Results:
      Compared with the OTS implant study arm, the CIM implant study arm showed
      significantly lower transfusion rates (2.4% vs 11.6%; P = .005); a lower adverse
      event rate at both discharge (CIM 3.3% vs OTS 14.1%; P = .003) and 90 days after
      discharge (CIM 8.1% vs OTS 18.2%; P = .023); and a smaller percentage of patients
      were discharged to a rehabilitation or other acute care facility (4.8% vs 16.4%;
      P = .003). Total average real hospital cost for the TKA hospitalization between
      the 2 groups were nearly identical (CIM $16,192 vs OTS $16,240; P = .913).
      Finally, the risk-adjusted per patient total cost of care showed a net savings of
      $913.87 (P = .240) per patient for the CIM-TKA group, for bundle of care
      including the preoperative computed tomography scan, TKA hospitalization, and
      discharge disposition. Conclusions: Patients treated with a CIM implant had
      significantly lower transfusion rates, fewer adverse event rates, and were less
      likely to be discharged to a rehabilitation facility or another acute care
      facility. These outcomes were achieved without increasing costs.

PMID- 29204494
TI  - A classification-based approach to the patella in revision total knee
      arthroplasty.
AB  - Background: There is a paucity of data to guide management of the patella in
      revision total knee arthroplasty (RTKA). The purpose of this study was to review
      our experience with patellar management in RTKA. Methods: We retrospectively
      reviewed 422 consecutive RTKAs at a minimum of 2 years (mean, 42 months).
      Patellar management was guided by a classification that considered stability,
      size, and position of the implanted patellar component, thickness/quality of
      remaining bone stock, and extensor mechanism competence. Results: Management in
      304 aseptic revisions included retention of a well-fixed component in 212 (69.7%)
      and revision using an all-polyethylene component in 46 (15.1%). Patella-related
      complications included 5 extensor mechanism ruptures (1.6%), 3 cases of patellar
      maltracking (1.0%), and 2 periprosthetic patellar fractures (0.7%). Of 118 2
      stage revisions for infection, an all-polyethylene component was used in 88
      (74.6%), patelloplasty in 20 (16.9%), and patellectomy in 7 (5.9%). Patella
      related complications included 4 cases of patellar maltracking (3.4%), 3 extensor
      mechanism ruptures (2.5%), and 1 periprosthetic patellar fracture (0.8%).
      Conclusions: Septic revisions required concomitant lateral releases more
      frequently (38.1% vs 10.9%; P < .02) but had a similar rate of patellar
      complications (6.8% vs 3.3%; P = .40). No cases required rerevision specifically
      for failure of the patellar component. Patients who had a patelloplasty had worse
      postoperative Knee Society functional scores than those with a retained or
      revised patellar component. In most aseptic RTKAs, a well-fixed patellar
      component can be retained. If revision is required, a standard polyethylene
      component is sufficient in most septic and aseptic revisions. Rerevisions related
      to the patellar component are infrequent.

PMID- 29204495
TI  - Radiolucencies surrounding acetabular components with three-dimensional coatings:
      artifact or real?
AB  - Background: Several 2-dimensional and 3-dimensional surfaces are available for
      cementless acetabular fixation. Plain radiographs are used to assess
      osseointegration; however, the radiographs are limited by their inability to
      capture the bone fixation process occurring over the 3-dimensional cup surface.
      In this cadaveric study, we compared the bone apposition between 2-dimensional
      and 3-dimensional cups. Methods: Both types of cups were implanted in 6 cadavers
      and pelvic radiographs obtained. Each cup was resected from the pelvis with
      adequate bone around it, and subsequently embedded in a polymer. Six sections of
      each cup were obtained to examine the metal and bone interface. Photographs and
      contact radiograph images were obtained for each section, and these were graded
      to arrive at percent metal-bone contact values for the cups. Results: On average,
      <30% of the cups' areas displayed radiolucencies on the pelvic radiographs for
      both cup types. For the section images and radiographs, there was about 80%
      aggregate contact between the cups and surrounding bone in both cup types. In the
      3-dimensional cups group, some inconsistencies were found between the section
      photographs and the corresponding radiograph images. The radiolucencies observed
      on the section radiograph could not always be correlated with metal to bone gap
      on the section photograph. Conclusions: Good metal-bone contact (75% + contact
      area) was observed on both cup types. The inconsistencies found in the 3
      dimensional cup group may be because of the interaction of radiographs with the
      unique porous cup surface resulting in artifactual radiolucencies.

PMID- 29204496
TI  - Comparison of postarthroplasty functional outcomes in skilled nursing facilities
      among Medicare and Managed Care beneficiaries.
AB  - Background: After home health care, the skilled nursing facility (SNF) is the
      most commonly used postacute care modality, among Medicare beneficiaries, after
      total joint arthroplasty. Prior studies demonstrated that a loss in postsurgical
      ambulatory gains is incurred in the interval between hospital discharge and
      arrival at the SNF. The aim of this present study is to determine the
      consequences of that loss in function, as well as compare SNF-related outcomes in
      patients with Medicare vs Managed Care (MC) insurance. Methods: We conducted a
      retrospective analysis of 80 patients (54 Medicare and 26 MC) who attended an SNF
      after hospitalization for total joint arthroplasty. Outcomes from physical
      therapy records were abstracted from each patient's SNF file. Results: There was
      an approximately 40% drop-off in gait achievements between hospital discharge and
      SNF admission. This decline in ambulation was significantly greater in Medicare
      patients (Medicare: 94.6 +/- 123.2 ft, MC: 40.0 +/- 48.9 ft, P = .034). Larger
      reductions in gait achievements between hospital discharge and SNF admission were
      significantly correlated with longer SNF lengths of stay and poorer gait
      achievements by SNF discharge. Patients with MC insurance made significant
      improvements in gait training at the SNF beyond that which was acquired at the
      hospital, whereas Medicare patients did not (PMedicare  = .28, PMC  = .003).
      Conclusions: Large losses in motor function between hospital discharge and SNF
      admission were associated with poor functional outcomes and longer stays at the
      SNF. These effects were more pronounced in Medicare patients than those with MC
      insurance.

PMID- 29204497
TI  - Decreased risk of knee buckling with adductor canal block versus femoral nerve
      block in total knee arthroplasty: a retrospective cohort study.
AB  - Background: Femoral nerve (FNB) and adductor canal blocks (ACB) are used in the
      setting of total knee arthroplasty (TKA), but neither has been demonstrated to be
      clearly superior. Although dynamometer studies have shown ACBs spare
      perioperative quadriceps function when compared to FNBs, ACBs have been widely
      adopted in orthopaedic surgery without significant evidence that they decrease
      the risk of perioperative falls. Methods: All patients who received single-shot
      FNB (129 patients) or ACB (150 patients) at our institution for unilateral
      primary TKA from April 2014 to September 2015 were retrospectively reviewed for
      perioperative falls or near-falls during physical therapy and inpatient care.
      Results: There were significantly more "near-falls" with documented episodes of
      knee buckling in the FNB group (17 vs 3, P = .0004). These patients' first
      buckling episode occurred at an average of 21.1 hours postoperatively (standard
      deviation 5.83, range 13.83-41.15). There were no significant differences in pain
      scores between the 2 groups at any of the time periods measured; however,
      patients in the FNB group consumed significantly fewer opioids on postoperative
      day 1 than the ACB group (59 morphine equivalents vs 73, P = .004). Conclusions:
      A significantly higher rate of near-falls with knee buckling during in-hospital
      physical therapy was discovered in the FNB group. With increasing numbers of TKAs
      being performed on a "fast-track" discharge model, these results must be
      seriously considered, particularly in patients planning to go home the same day,
      to reduce the risk of postoperative falls. These data support the recent clinical
      data trend favoring ACB over FNB in orthopaedic surgery.

PMID- 29204498
TI  - Strategies for reducing implant costs in the revision total knee arthroplasty
      episode of care.
AB  - Background: Implant price has been identified as a significant contributing
      factor to high costs associated with revision total knee arthroplasty (rTKA). The
      goal of this study is to analyze the cost of implants used in rTKAs and to
      compare this pricing with 2 alternative pricing models. Methods: Using our
      institutional database, we identified 52 patients from January 1, 2014 to
      December 31, 2014. Average cost of components for each case was calculated and
      compared to the total hospital cost for that admission. Costs for an all
      component revision were then compared to a proposed "direct to hospital" (DTH)
      standardized pricing model and a fixed price revision option. Potential savings
      were calculated from these figures. Results: On average, 28% of the total
      hospital cost was spent on implants for rTKA. The average cost for revision of
      all components was $13,640 and ranged from $3000 to $28,000. On average, this
      represented 32.7% of the total hospital cost. Direct to hospital implant pricing
      could potentially save approximately $7000 per rTKA, and the fixed pricing model
      could provide a further $1000 reduction per rTKA-potentially saving $8000 per
      case on implants alone. Conclusions: Alternative implant pricing models could
      help lower the total cost of rTKA, which would allow hospitals to achieve
      significant cost containment.

PMID- 29204499
TI  - Variance in predicted cup size by 2-dimensional vs 3-dimensional computerized
      tomography-based templating in primary total hip arthroplasty.
AB  - Background: Preoperative total hip arthroplasty templating can be performed with
      radiographs using acetate prints, digital viewing software, or with computed
      tomography (CT) images. Our hypothesis is that 3D templating is more precise and
      accurate with cup size prediction as compared to 2D templating with acetate
      prints and digital templating software. Methods: Data collected from 45 patients
      undergoing robotic-assisted total hip arthroplasty compared cup sizes templated
      on acetate prints and OrthoView software to MAKOplasty software that uses CT
      scan. Kappa analysis determined strength of agreement between each templating
      modality and the final size used. t tests compared mean cup-size variance from
      the final size for each templating technique. Interclass correlation coefficient
      (ICC) determined reliability of digital and acetate planning by comparing
      predictions of the operating surgeon and a blinded adult reconstructive fellow.
      Results: The Kappa values for CT-guided, digital, and acetate templating with the
      final size was 0.974, 0.233, and 0.262, respectively. Both digital and acetate
      templating significantly overpredicted cup size, compared to CT-guided methods (P
      < .001). There was no significant difference between digital and acetate
      templating (P = .117). Interclass correlation coefficient value for digital and
      acetate templating was 0.928 and 0.931, respectively. Conclusions: CT-guided
      planning more accurately predicts hip implant cup size when compared to the
      significant overpredictions of digital and acetate templating. CT-guided
      templating may also lead to better outcomes due to bone stock preservation from a
      smaller and more accurate cup size predicted than that of digital and acetate
      predictions.

PMID- 29204500
TI  - Intraoperative chlorhexidine irrigation to prevent infection in total hip and
      knee arthroplasty.
AB  - Background: Surgical site irrigation during total hip (THA) and total knee (TKA)
      arthroplasty is a routine practice among orthopaedic surgeons to prevent
      periprosthetic joint infection. The purpose of this study was to evaluate the
      effect of chlorhexidine gluconate (CHG) irrigation on infection rates following
      THA and TKA. Methods: Arthroplasties performed before September 2014 served as
      controls. THA performed before September 2014 (N = 253) underwent intraoperative
      irrigation with 0.9% saline followed by a 2-minute soak with <2% dilute povidone
      iodine. TKA (N = 411) patients underwent only intraoperative saline irrigation.
      After October 2014, all patients (248 TKA and 138 THA) received intraoperative
      irrigation with 0.9% saline and periodic 0.05% CHG solution followed by a final 1
      minute soak in CHG with immediate closure afterward. Results: In this 2:1
      comparison of consecutive patients, there were no differences in patient
      demographics between the 2 groups. No difference was noted in wound healing
      concerns subjectively, and no statistically significant association in
      nonsurgical site infections, superficial surgical site infection, and deep
      surgical site infection rates between the 2 groups (nonsurgical site infections
      [THA: P = .244, TKA: P = .125]; superficial surgical site infection [THA: P =
      .555, TKA: P = .913]; and deep surgical site infection [THA: P = .302, TKA: P =
      .534]). Conclusions: We were unable to discern a difference in infection rates
      between chlorhexidine irrigation and our prior protocols using dilute Betadine
      for THA and 0.9% saline for TKA. The theoretic advantages of dilute CHG retention
      during closure appear to be safe without infectious concerns.

PMID- 29204501
TI  - Academic productivity among fellowship associated adult total joint
      reconstruction surgeons.
AB  - Background: The Hirsch index (h-index) is a measure that evaluates both research
      volume and quality-taking into consideration both publications and citations of a
      single author. No prior work has evaluated academic productivity and
      contributions to the literature of adult total joint replacement surgeons. This
      study uses h-index to benchmark the academic impact and identify characteristics
      associated with productivity of faculty members at joint replacement fellowships.
      Methods: Adult reconstruction fellowship programs were obtained via the American
      Association of Hip and Knee Surgeons website. Via the San Francisco match and
      program-specific websites, program characteristics (Accreditation Council for
      Graduate Medical Education approval, academic affiliation, region, number of
      fellows, fellow research requirement), associated faculty members, and faculty
      specific characteristics (gender, academic title, formal fellowship training,
      years in practice) were obtained. H-index and total faculty publications served
      as primary outcome measures. Multivariable linear regression determined
      statistical significance. Results: Sixty-six adult total joint reconstruction
      fellowship programs were identified: 30% were Accreditation Council for Graduate
      Medical Education approved and 73% had an academic affiliation. At these
      institutions, 375 adult reconstruction surgeons were identified; 98.1% were men
      and 85.3% had formal arthroplasty fellowship training. Average number of
      publications per faculty member was 50.1 (standard deviation 76.8; range 0-588);
      mean h-index was 12.8 (standard deviation 13.8; range 0-67). Number of fellows,
      faculty academic title, years in practice, and formal fellowship training had a
      significant (P < .05) positive correlation with both h-index and total
      publications. Conclusions: The statistical overview presented in this work can
      help total joint surgeons quantitatively benchmark their academic performance
      against that of their peers.

PMID- 29204502
TI  - Preoperative radiographic valgus alignment predicts the extent of lateral soft
      tissue release and need for constraint in valgus total knee arthroplasty.
AB  - Background: In total knee arthroplasty (TKA) for valgus knees, the decision to
      use a constrained implant is often made intraoperatively depending on the extent
      of soft tissue releases performed and residual soft tissue imbalance. The purpose
      of this study is to determine if preoperative radiographic criteria of valgus
      knees can predict the extent of soft tissue releases required and the level of
      constraint needed to balance the knee during TKA. Methods: A single surgeon's 807
      consecutive TKA standing hip-knee-ankle radiographs from 2007-2012 were analyzed.
      One hundred eighty-seven valgus knees were identified and annotated. Statistical
      univariate and multivariate analyses were performed for both outcomes, lateral
      release and articulation, to assess the association with risk factors of gender,
      age, and preoperative radiographic markers of valgus deformity. A P-value <.05
      represented a significant difference between groups. Results: Use of a
      constrained articulation was associated with increased valgus deformity
      (mechanical hip-knee-ankle angle, P < .0001) and extent of lateral soft tissue
      release (P < .0001). No relationship existed between the use of a constrained
      articulation and age or gender (P > .05). A preoperative anatomic tibiofemoral
      valgus angle of >16.8 degrees  was associated with the use of a constrained
      articulation during surgery. Conclusions: Our data demonstrate that preoperative
      radiographic characteristics of the valgus knee can be utilized to predict the
      extent of lateral soft tissue release and whether a constrained articulation will
      be required in TKA. This will provide surgeons with useful information to offer
      accurate preoperative counseling to patients and to ensure that the appropriate
      prosthetic parts are available during surgery.

PMID- 29204503
TI  - Bicompartmental knee arthroplasty vs total knee arthroplasty for the treatment of
      medial compartment and patellofemoral osteoarthritis.
AB  - Background: Interest in bicompartmental knee arthroplasty (BKA) for the treatment
      of medial patellofemoral osteoarthritis (MPFOA) has grown in recent years because
      BKA offers a bone and ligament-preserving alternative to total knee arthroplasty
      (TKA). BKA only resurfaces the diseased compartments, while preserving
      proprioception and native knee kinematics. Therefore, the objective of this study
      is to assess knee function, perioperative morbidity, and implant survivability in
      patients undergoing BKA vs TKA for MPFOA. Methods: The databases MEDLINE, PUBMED,
      and EMBASE were systematically searched. Randomized controlled trials and
      nonrandomized comparative studies comparing BKA with TKA for the treatment of
      MPFOA were included for further analysis. The primary outcome of interest was
      knee function. Secondary outcomes included range of movement, operation length,
      intraoperative blood loss, hospital length of stay, postoperative complications,
      and rate of revision length. The quality of evidence was evaluated using the
      GRADE approach. Meta-analysis was performed by pooling the results of the
      selected studies when possible. Results: Six studies were selected for inclusion
      (4 prospective studies and 2 retrospective cohort studies). In total, 274
      patients and 277 knees were included for analysis. There were no significant
      differences between the 2 groups at any time points in terms of knee function,
      length of stay, complication rate, or revision rate, when monolithic BKA designs
      were controlled for. BKA did result in significantly decreased intraoperative
      blood loss, at the expense of increased operative length compared with TKA.
      Conclusions: The use of modular BKA for MPFOA is comparable with TKA in terms of
      short-term function, complication rate, and revision rate. BKA reduces
      intraoperative blood losses, but it is also more technically demanding, resulting
      in increased operation length. The use of modular BKA has acceptable short-term
      outcomes, but more long-term data are needed before it can be recommended for
      routine use in the treatment of MPFOA. The selection of modular BKA should be
      determined on a patient-specific basis. Currently, there is no evidence to
      suggest the use of monolithic BKA designs because of their high revision and
      failure rate.

PMID- 29204505
TI  - Of Mice and Men and Metaplasia.

PMID- 29204506
TI  - A Twist in the Tale of a Pig Model of Short-Bowel Syndrome.

PMID- 29204504
TI  - Self-renewing Monolayer of Primary Colonic or Rectal Epithelial Cells.
AB  - Background & Aims: Three-dimensional organoid culture has fundamentally changed
      the in vitro study of intestinal biology enabling novel assays; however, its use
      is limited because of an inaccessible luminal compartment and challenges to data
      gathering in a three-dimensional hydrogel matrix. Long-lived, self-renewing 2
      dimensional (2-D) tissue cultured from primary colon cells has not been
      accomplished. Methods: The surface matrix and chemical factors that sustain 2-D
      mouse colonic and human rectal epithelial cell monolayers with cell repertoires
      comparable to that in vivo were identified. Results: The monolayers formed
      organoids or colonoids when placed in standard Matrigel culture. As with the
      colonoids, the monolayers exhibited compartmentalization of proliferative and
      differentiated cells, with proliferative cells located near the peripheral edges
      of growing monolayers and differentiated cells predominated in the central
      regions. Screening of 77 dietary compounds and metabolites revealed altered
      proliferation or differentiation of the murine colonic epithelium. When exposed
      to a subset of the compound library, murine organoids exhibited similar responses
      to that of the monolayer but with differences that were likely attributable to
      the inaccessible organoid lumen. The response of the human primary epithelium to
      a compound subset was distinct from that of both the murine primary epithelium
      and human tumor cells. Conclusions: This study demonstrates that a self-renewing
      2-D murine and human monolayer derived from primary cells can serve as a
      physiologically relevant assay system for study of stem cell renewal and
      differentiation and for compound screening. The platform holds transformative
      potential for personalized and precision medicine and can be applied to emerging
      areas of disease modeling and microbiome studies.

PMID- 29204507
TI  - Clocking the Pace of Organoid Research.

PMID- 29204508
TI  - Advancing Intestinal Organoid Technology Toward Regenerative Medicine.
AB  - With the emergence of technologies to culture intestinal epithelial cells in
      vitro as various forms of intestinal organoids, there is growing interest in
      using such cultured intestinal cells as a source for tissue engineering and
      regenerative medicine. One such approach would be to combine the organoid
      technology with methodologies to engineer the culture environment, particularly
      the three-dimensional scaffold materials, to generate intestines that exquisitely
      recapitulate their original structures and functions. Another approach to use
      organoids for regenerative medicine would be to urge them to mature into
      functional intestines by implanting them into hosts. This process includes the
      tissue-engineered small intestine that uses synthetic scaffolds for tissue
      regeneration and direct organoid transplantation that takes advantage of
      submucosal tissues in the native intestines as a scaffold. Further study in these
      subfields could lead to the development of therapeutic options to use different
      types of organoids with various cell types in regenerative medicine for
      intestinal diseases in humans.

PMID- 29204510
TI  - Ovarian yolk sac tumor coexisting with epithelial ovarian cancer: An aggressive
      rare entity.
AB  - Yolk sac tumor (YST) is the second most common subtype of ovarian germ cell
      tumors. It usually occurs in the second and third decades of life and is rare in
      postmenopausal women. In postmenopausal women, YST is commonly an aggressive
      tumor and can present as a pure germ cell component or as a mixed component with
      other germ cell or epithelial components. The recognition of this histological
      subtype is important not only for differential diagnosis but also for determining
      prognosis and treatment decisions. In this case report, we describe a 61-year-old
      woman with YST coexisting with epithelial carcinoma focusing on the efficacy of
      systemic therapies.

PMID- 29204509
TI  - Evaluation of semi-automatic image analysis tools for cerebrospinal fluid
      electrophoresis of IgG oligoclonal bands.
AB  - Background: IgG concentrations in cerebrospinal fluid generally range from 20 to
      45 mg/L. In multiple sclerosis immune reactions lead to intrathecal synthesis of
      specific IgGs that can be detected in biological fluid samples both
      quantitatively and qualitatively by isoelectric focusing of supplementary
      oligoclonal IgG bands. Method: A simple tool, using the MATLAB application, to
      facilitate and improve isoelectric focusing profile analysis is presented and
      evaluated in terms of its sensitivity, repeatability and reproducibility. A
      comparison between human readers and semi-automatic method has also been
      performed. Results: Results from the semi-automatic method were found to be
      equivalent or superior to generally employed laboratory methods. Repeatability
      analysis for semi-automatic processing yielded coefficients of variation (CVs) in
      the 3-7% range, and using a sample with an estimated IgG concentration of 200
      mg/L, four bands were still visible after dilution to 5 mg/L, corresponding to
      band concentrations of 1.1-1.6 mg/L. Discordances between visual inspection and
      automatic analysis only appear at threshold levels for interpretation (the gray
      zone). Conclusion: The semi-automatic method has acceptable performance for
      routine implementation.

PMID- 29204511
TI  - SMARCA4 germline gene mutation in a patient with epithelial ovarian: A case
      report.
AB  - Background: SMARCA4 is gene whose protein product participates in chromatin
      remodeling. Somatic mutations in this gene are associated with non-small cell
      lung cancer and malignant rhabdoid tumors, and both germline and somatic
      mutations are seen with small cell carcinoma of the ovary, hypercalcemic type. To
      date, there are no data identifying an association with more common epithelial
      carcinomas of the ovary. Case: The patient is a 57-year-old female without any
      significant family history of cancer, diagnosed with high-grade serous carcinoma
      of the ovary. Per guideline, she underwent genetic testing, and was found to have
      a deleterious germline SMARCA4 mutation. She was treated with standard
      chemotherapy and an optimal tumor reduction, with a complete response to
      treatment. Conclusion: The etiology of this patient's high-grade serous carcinoma
      is unknown. If the SMARCA4 gene plays a role in serous ovarian carcinoma it is
      with variable expressivity. Further investigation into the role of SMARCA4 as a
      susceptibility gene for epithelial ovarian cancer is warranted.

PMID- 29204512
TI  - BRCA and lynch syndrome-associated ovarian cancers behave differently.

PMID- 29204513
TI  - Motherhood, Fatherhood and Midlife Weight Gain in a US Cohort: Associations
      differ by race/ethnicity and socioeconomic position.
AB  - While there is an association of greater short-term weight gain with childbearing
      among women, less is known about longer-term weight gain, whether men have
      similar gains, and how this varies by race/ethnicity and socioeconomic position.
      Our cohort consisted of a nationally representative sample of 7,356 Americans
      with oversampling of Black and Hispanic populations. We estimated the
      associations between number of biological children and parental weight, measured
      as both change in self-reported body mass index (BMI) from age 18 and
      overweight/obese status (BMI >= 25) at age 40. We performed multivariate linear
      and logistic regression analysis and tested for effect modification by gender.
      For change in BMI, men gained on average 0.28 BMI (95% CI: (0.01, 0.55)) units
      per child, while women gained 0.13 units per child (95% CI: (-0.22, 0.48)). The
      adjusted odds ratios for overweight/obesity associated with each child were 1.32
      (95% CI: (1.11, 1.58)) for men and 1.15 (95% CI: (1.01, 1.31)) for women.
      Stratified analyses by race/ethnicity and socioeconomic position suggested that
      the observed full-cohort differences were driven primarily by gendered
      differences in low-income Hispanics and Whites - with the greatest associations
      among Hispanic men. For example, among low-income Hispanic men we observed a
      positive relationship between the number of children and weight change by age 40,
      with average weight change of 0.47 units per child (95%CI: (-0.65, 1.59 For low
      income Hispanic women, however, the average weight change was -0.59 units per
      child (95%CI: (-1.70, 0.47), and the P-value for the test of interaction between
      gender and number of children was P < 0.001. Our findings suggest that the shared
      social and economic aspects of raising children play an important role in
      determining parental weight at mid-life.

PMID- 29204514
TI  - Tuberculosis among Jimma University Undergraduate Students: First Insight about
      the Burden of Tuberculosis in Ethiopia Universities-Cross-Sectional Study.
AB  - Background: Ethiopian universities are facilities where students live in relative
      overcrowding condition. This might favor the chance of tuberculosis transmission
      among students. This study was done to determine the magnitude and associated
      factors of tuberculosis among Jimma University students. Methods: A cross
      sectional study was done from February 2015 to July 2015. Hundred twenty-nine
      consented participants were interviewed using structured questionnaire.
      Biological specimens were collected and cultured on Mycobacterium Growth
      Indicator Tube. Mycobacterium tuberculosis complex verification was done by SD
      BIOLINE TB Ag MPT64 Rapid test. Frequency distribution, logistic regression, and
      independent sample t-test were used to analyze the data using SPSS Version 20.
      Result: Magnitude of all forms of tuberculosis among Jimma University
      undergraduate students was 209.1 per 100000-student population. Contact history
      [AOR: 4.76, 95% CI (1.31-17.31)], smoking [AOR: 6.67, 95% CI (1.51-29.44)], khat
      chewing [AOR: 5.56, 95% CI (1.66-18.69)], and low body mass index [AOR: 5.37, 95%
      CI (1.46-19.78)] were determinants of tuberculosis. Conclusion: The magnitude of
      tuberculosis among Jimma University undergraduate students is high. TB is
      associated with previous tuberculosis patient contact and behavioral factors.
      Hence, students with these risk factors should be given enough attention for the
      control of TB in Jimma University.

PMID- 29204515
TI  - Parastomal Hernia Repair with Intraperitoneal Mesh.
AB  - Purpose: Parastomal hernia is a common complication following a stoma and may
      cause leakage or incarceration. No optimal treatment has been established, and
      existing methods using mesh repair are associated with high recurrence rates and
      a considerable risk for short- and long-term complications including death. A
      double-layer intraperitoneal on-lay mesh (IPOM), the Parastomal Hernia Patch
      (BARDTM), consisting of ePTFE and polypropylene, has been developed and tailored
      to avoid recurrence. To evaluate the safety of and recurrence rate using this
      mesh, a nonrandomised prospective multicentre study was performed. Method: Fifty
      patients requiring surgery for parastomal hernia were enrolled. Clinical
      examination and CT scan prior to surgery were performed. All patients were
      operated on using the Parastomal Hernia Patch (BARD). Postoperative follow-up at
      one month and one year was scheduled to detect complications and hernia
      recurrence. Results: The postoperative complication rate at one month was 15/50
      (30%). The parastomal hernia recurrence rate at one year was 11/50 (22%). The
      reoperation rate at one month was 7/50 (14%), and further 5/50 (10%) patients
      were reoperated on during the following eleven months.

PMID- 29204517
TI  - Proteomic analysis of AQP11-null kidney: Proximal tubular type polycystic kidney
      disease.
AB  - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of
      polycystins (PC-1 or PC-2), in which cysts start from the collecting duct to
      extend to all nephron segments with eventual end stage renal failure. The cyst
      development is attenuated by a vasopressin V2 receptor antagonist tolvaptan
      which, however, will not affect proximal tubule cysts devoid of V2 receptor.
      Aquaporin-11 (AQP11) is expressed selectively in the proximal tubule of the
      kidney and AQP11-null kidneys have a disruptive PC-1 trafficking to the plasma
      membrane to develop polycystic kidneys. Here, we analyzed AQP11-null kidneys at
      the beginning of cyst formation by quantitative proteomic analysis using Tandem
      Mass Tag (TMT). Among ~ 1200 identified proteins, 124 proteins were differently
      expressed by > 1.5 or < 0.8 fold change. A pancreatic stone inhibitor or a growth
      factor, lithostathine-1 (Reg1) was most enhanced by 5 folds which was confirmed
      by western blot, while mitochondria-related proteins were downregulated. The
      identified proteins will be new target molecules for the treatment of proximal
      tubular cysts and helpful to explore the functional roles of AQP11 in the kidney.

PMID- 29204516
TI  - Cross-Laboratory Analysis of Brain Cell Type Transcriptomes with Applications to
      Interpretation of Bulk Tissue Data.
AB  - Establishing the molecular diversity of cell types is crucial for the study of
      the nervous system. We compiled a cross-laboratory database of mouse brain cell
      type-specific transcriptomes from 36 major cell types from across the mammalian
      brain using rigorously curated published data from pooled cell type microarray
      and single-cell RNA-sequencing (RNA-seq) studies. We used these data to identify
      cell type-specific marker genes, discovering a substantial number of novel
      markers, many of which we validated using computational and experimental
      approaches. We further demonstrate that summarized expression of marker gene sets
      (MGSs) in bulk tissue data can be used to estimate the relative cell type
      abundance across samples. To facilitate use of this expanding resource, we
      provide a user-friendly web interface at www.neuroexpresso.org.

PMID- 29204518
TI  - The pervasive crisis of diminishing radiation therapy access for vulnerable
      populations in the United States, part 1: African-American patients.
AB  - Introduction: African Americans experience the highest burden of cancer incidence
      and mortality in the United States and have been persistently less likely to
      receive interventional care, even when such care has been proven superior to
      conservative management by randomized controlled trials. The presence of
      disparities in access to radiation therapy (RT) for African American cancer
      patients has rarely been examined in an expansive fashion. Methods and materials:
      An extensive literature search was performed using the PubMed database to examine
      studies investigating disparities in RT access for African Americans. Results: A
      total of 55 studies were found, spanning 11 organ systems. Disparities in access
      to RT for African Americans were most prominently study in cancers of the breast
      (23 studies), prostate (7 studies), gynecologic system (5 studies), and
      hematologic system (5 studies). Disparities in RT access for African Americans
      were prevalent regardless of organ system studied and often occurred
      independently of socioeconomic status. Fifty of 55 studies (91%) involved
      analysis of a population-based database such as Surveillance, Epidemiology and
      End Result (SEER; 26 studies), SEER-Medicare (5 studies), National Cancer
      Database (3 studies), or a state tumor registry (13 studies). Conclusions:
      African Americans in the United States have diminished access to RT compared with
      Caucasian patients, independent of but often in concert with low socioeconomic
      status. These findings underscore the importance of finding systemic and
      systematic solutions to address these inequalities to reduce the barriers that
      patient race provides in receipt of optimal cancer care.

PMID- 29204519
TI  - Cardiac-sparing radiation therapy using positioning breast shell for patients
      with left-sided breast cancer who are ineligible for breath-hold techniques.
AB  - Purpose: Patients with left-sided breast cancer (LSBC) are at increased risk of
      cardiac morbidity from adjuvant breast radiation therapy (ABRT). Breath-hold (BH)
      techniques substantially reduce the radiation received by heart during radiation
      therapy for LSBC. However, a subset of patients with LSBC are ineligible for BH
      techniques due to an inability to breath-hold or because of other comorbidities.
      To reduce radiation to the heart, we routinely use a custom-made breast shell for
      the treatment of patients with LSBC who are ineligible for BH techniques. This
      study evaluates the dosimetric impact of using a breast shell for patients with
      LSBC undergoing ABRT. Methods and materials: Sixteen consecutive patients with
      LSBC who failed BH and underwent ABRT using a breast shell during the period of
      2014 to 2016 were identified. Treatment was planned using field-in-field tangents
      with a prescribed dose of 42.5 Gy in 16 fractions. Comparisons between plans with
      and without a shell were made for each patient using a paired t test to quantify
      the sparing of organs at risk (OARs) and target coverage. Results: There was no
      statistically significant difference in the planning target volume of breast
      coverage. A statistically significant improvement was observed in sparing the
      heart, left ventricle (LV), and ipsilateral lung (P-value < .001). Plans with the
      shell spared OARs better than the no-shell plans with a mean dose of 2.15 Gy
      versus 5.15 Gy (58.2% reduction) to the heart, 3.27 Gy versus 9.00 Gy (63.7%
      reduction) to the LV, and 5.16 Gy versus 7.95 Gy (35% reduction) to the
      ipsilateral lung. The irradiated volumes of OARs for plans with and without shell
      are 13.3 cc versus 59.5 cc (77.6% reduction) for the heart, 6.2 cc versus 33.2 cc
      (81.2% reduction) for the LV, and 92.8 cc versus 162.5 cc (42.9% reduction) for
      the ipsilateral lung. Conclusions: A positioning breast shell offers significant
      benefit in terms of sparing the heart for patients with LSBC who are ineligible
      for BH techniques. It also can be used as a simple cardiac-sparing alternative in
      centers without BH capability.

PMID- 29204520
TI  - Comprehensive assessment of circulating immune cell populations in response to
      stereotactic body radiation therapy in patients with liver cancer.
AB  - Stereotactic body radiation therapy (SBRT) can positively influence an antitumor
      immune response by inducing necrotic cell death. SBRT also been shown to
      eliminate tumors outside the radiation therapy field through an immune-mediated
      process known as the abscopal effect. Recent advances in immunotherapy may
      provide new therapeutic approaches for patients with liver cancer. Therefore,
      understanding the immune status of patients with cancer will likely guide how
      immunotherapy might be used in combination with SBRT. We hypothesized that we
      would observe changes in circulating blood immune cell populations of patients
      who received SBRT for liver tumors. Therefore, we assessed 110 immunophenotypes
      in the peripheral blood of 10 patients with liver cancer or metastases to the
      liver pretreatment and 2 posttreatment time points. Patients with liver cancer
      and metastatic patients both exhibited several immunophenotypic abnormalities at
      baseline compared with a group of healthy volunteer controls. In longitudinal
      studies, SBRT caused a specific reduction in CD3+ T cell counts and immature
      CD56brCD16- NK cell counts. The immune profiling and potential identification of
      circulating biomarkers shown here could lead to the design of combinatorial
      approaches with SBRT and immunotherapy to optimize the timing of treatment and
      direct the most effective immunotherapy with SBRT.

PMID- 29204521
TI  - Factors influencing the utilization of prophylactic cranial irradiation in
      patients with limited-stage small cell lung cancer.
AB  - Purpose: Brain metastases are common in patients with limited-stage small cell
      lung cancer (LS-SCLC) due to the inability of most chemotherapeutics to penetrate
      the blood-brain barrier. Prophylactic cranial irradiation (PCI) is therefore
      recommended for use in patients with a good response to concurrent
      chemoradiotherapy. However, PCI is not always delivered; therefore, we
      investigated the reasons for PCI omission in patients who underwent therapy with
      curative intent. Methods and materials: We retrospectively reviewed all patients
      with LS-SCLC who were treated with curative intent at our institution. Overall
      survival and cumulative incidence of brain metastasis were estimated by the
      Kaplan-Meier method. The Pearson chi2 test and Mann-Whitney U test were used to
      examine factors associated with PCI use, and prognostic factors were analyzed
      with Cox proportional hazards modeling. Results: We examined 208 patients who
      were treated for LS-SCLC at our institution. A total of 115 patients (55%)
      received PCI. The most common documented reason for PCI omission was patient
      refusal due to neurotoxicity concerns (38%). Physician assessment of being
      medically unfit (33%) and of advanced age (8%) were the second and third most
      common reasons, respectively. Karnofsky performance status and clinical American
      Joint Committee on Cancer stage but not PCI were significantly associated with
      overall survival. Only clinical stage remained an independent factor on
      multivariate analysis. Conclusions: Approximately half of patients with LS-SCLC
      ultimately receive PCI, generally for guideline-recommended reasons. The most
      common reason for PCI omission was patient concerns regarding neurotoxicity.
      Efforts to decrease PCI neurotoxicity, including hippocampal-sparing radiation
      and memantine use, may increase the use of this survival-improving intervention
      in eligible patients with LS-SCLC.

PMID- 29204522
TI  - Single fraction stereotactic radiosurgery for multiple brain metastases.
AB  - Introduction: Due to the neurocognitive side effects of whole brain radiation
      therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing
      frequency. The use of SRS is expanding for patients with multiple (>4) brain
      metastases (BM). This study summarizes our institutional experience with single
      fraction, linear-accelerator-based SRS for multiple BM. Methods and materials:
      All patients who were treated between January 1, 2013, and September 30, 2015,
      with single-fraction SRS for >=4 BM were included in this institutional review
      board-approved, retrospective, single-institution study. Patients were treated
      with linear accelerator-based image guided SRS. Results: A total of 59 patients
      with >=4 BM were treated with single-fraction SRS. The median follow-up was 15.2
      months, and the median overall survival for the entire cohort was 5.8 months. The
      median number of treated lesions per patient was 5 (range, 4-23). Per patient,
      the median planning target volume (PTV) was 4.8 cc (range, 0.7-28.8 cc). The
      prescribed dose across all 380 BM for the 59 patients ranged from 7 to 20 Gy. The
      median of the mean dose to the total PTV was 19.5 Gy. Although the number of
      treated lesions (4-5 vs >=6) did not influence survival, better survival was
      noted for a total PTV <10 cc versus >=10 cc (7.1 vs 4.2 months, respectively; P =
      .0001). A mean dose of >=19 Gy to the entire PTV was also associated with
      increased survival (6.6 vs 5.0 months, respectively; P = .0172). Patients
      receiving a dose of >12 Gy to >=10 cc of normal brain had worse survival (5.1 vs
      8.6 months, respectively; P = .0028). Conclusion: In single-fraction SRS for
      patients with multiple BM, smaller total tumor volume, higher total dose, and
      lower volume of normal brain receiving >12 Gy were associated with increased
      survival. These data suggest that using SRS for the treatment of multiple BM is
      efficacious and that outcomes may be affected more by total tumor volume than by
      the number of lesions.

PMID- 29204523
TI  - Fractionated stereotactic radiation therapy for intact brain metastases.
AB  - Purpose: Limited data exist on fractionated stereotactic radiation therapy (FSRT)
      for brain metastases. We sought to evaluate the safety and efficacy of FSRT and
      further define its role in brain metastasis management. Methods and materials: A
      total of 72 patients were treated with linear accelerator-based FSRT to 182
      previously untreated, intact brain metastases. Targets received 25 or 30 Gy in 5
      fractions. All targets within the same course received the same prescription
      regardless of size. Toxicity was recorded per Radiation Therapy Oncology Group
      central nervous system toxicity criteria. Results: The median follow-up was 5
      months (range, 1-71 months). The Kaplan-Meier estimate of 12-month local control
      was 86%. Tumors <3 cm in diameter demonstrated improved 12-month local control of
      95% compared with 61% in tumors >=3 cm (P < .001). The Kaplan-Meier estimate of
      12-month local control was 91% in tumors treated with 30 Gy and only 75% in
      tumors treated with 25 Gy (P = .015). Tumor diameter >=3 cm resulted in increased
      local failure, and a 30 Gy prescription resulted in decreased local failure on
      multivariate analysis (hazard ratio [HR], 8.11 [range, 2.09-31.50; P = .003] and
      HR, 0.26 [range, 0.07-0.93; P = .038]). Grade 4 central nervous system toxicity
      occurred in 4 patients (6%) requiring surgery, and no patient experienced
      irreversible grade 3 or 5 toxicity. Increasing tumor diameter was associated with
      increased toxicity risk (HR, 2.45 [range, 1.04-5.742; P = .04]). Conclusions:
      FSRT for brain metastases appears to demonstrate a high rate of local control
      with minimal risk of severe toxicity. Local control appears to be associated with
      smaller tumor sizeand a higher prescription dose. FSRT is a viable option for
      those who are poor single-fraction candidates.

PMID- 29204524
TI  - Distant intracranial failure in melanoma brain metastases treated with
      stereotactic radiosurgery in the era of immunotherapy and targeted agents.
AB  - Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT)
      or targeted therapy is increasingly being used in the setting of melanoma brain
      metastases (MBMs). The synergistic properties of combination therapy are not well
      understood. We compared the distant intracranial failure rates of intact MBMs
      treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials:
      Combination therapy was defined as delivery of SRS within 3 months of IMT (anti
      CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary
      endpoint was distant intracranial failure after SRS, which was defined as any new
      MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using
      the Kaplan Meier method and Cox proportional hazards. Results: A total of 72
      patients with melanoma with 233 MBMs were treated between April 2006 and April
      2016. The number of MBMs within each treatment group was as follows: SRS: 121;
      SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9
      months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS +
      targeted therapy were 11.5%, 60%, and 10%, respectively (P < .001). On
      multivariate analysis, after adjusting for steroid use and number of MBMs, SRS +
      IMT remained associated with a significant reduction in distant intracranial
      failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI],
      0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI,
      0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS +
      targeted therapy was 66%, 85%, and 72%, respectively (P = .044). On multivariate
      analysis, after adjusting for dose, SRS + IMT remained associated with a
      significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI,
      0.14-0.95; P = .04). Conclusions: SRS with immunotherapy is associated with
      decreased distant and local intracranial failure compared with SRS alone.
      Prospective studies are warranted to validate this result.

PMID- 29204525
TI  - SBRT to adrenal metastases provides high local control with minimal toxicity.
AB  - Purpose: The adrenal glands are a common site of metastases because of their rich
      blood supply. Previously, adrenal metastases were treated with systemic
      chemotherapy or, more rarely, with surgical resection or palliative radiation
      therapy. Stereotactic body radiation therapy (SBRT) has recently emerged as an
      attractive noninvasive approach to definitively treat these lesions. We present
      our experience in treating adrenal metastases using SBRT and review the current
      literature. Methods and materials: This is a single-institution retrospective
      review of patients who received SBRT to adrenal metastases originating from
      various primary malignancies. Patients who were eligible for SBRT included those
      with limited metastatic disease (<=5 sites) with otherwise controlled metastatic
      disease and uncontrolled adrenal metastases. Results: Ten patients met the
      study's inclusion criteria and received SBRT doses of 30 to 48 Gy in 3 to 5
      fractions. Acute sequelae of SBRT treatment included 4 patients with grades 1 or
      2 nausea, 3 patients with grade 1 fatigue, and 1 with grade 1 diarrhea. The
      median follow-up was 6 months with a median overall survival of 9.9 months. One
      patient demonstrated progressive adrenal gland disease 18.8 months after SBRT
      treatment. Seven patients developed new distant metastases after treatment, with
      a median progression-free survival of 3.4 months. Three months after SBRT to the
      adrenal gland, 1 patient developed a gastrointestinal bleed. Conclusions: These
      results complement the limited existing body of literature by demonstrating that
      SBRT provides good control of treated adrenal gland metastasis; however, high
      grade late toxicities may occur. More stringent dose constraint limits may
      prevent associated serious adverse events.

PMID- 29204526
TI  - Outcomes and patterns of care in a nationwide cohort of pediatric
      medulloblastoma: Factors affecting proton therapy utilization.
AB  - Purpose: We examined national outcomes and patterns of care for pediatric
      patients with medulloblastoma (MB) in a large observational cohort. Methods and
      materials: Using the National Cancer Database, we evaluated the clinical features
      and survival outcomes of patients diagnosed with MB. The association between
      intervention, covariables, and outcome was assessed in a multivariable Cox
      analysis and through logistic regression analysis. Survival was estimated using
      the Kaplan-Meier method. Results: Among the 4032 patients in the National Cancer
      Database with pediatric brain tumors, 1300 patients met the inclusion criteria of
      histologic diagnosis, receipt of chemotherapy and radiation, and age <=18 years.
      The median age and follow-up were 8.4 years and 4.5 years, respectively. Five
      year survival was 79.0%. In the univariate analysis, inferior outcome (overall
      survival) was associated with rural residence (hazard ratio [HR], 2.78; 95%
      confidence interval [CI],1.47-5.29; P < .01) and histology (large cell; HR, 1.78;
      95% CI,1.08-2.94; P < .05). In multivariable analysis, both remained significant
      predictors of survival (large cell: HR, 1.68; P < .05; rural residence: HR, 2.74;
      P < .01). In 2013, the utilization rate of proton therapy (23% of patients) in
      the United States surpassed intensity modulate radiation therapy (16%), more
      frequently for patients with higher income (P < .05) or more favorable insurance
      status (P < .05). Conclusions: As one of the largest data sets on pediatric MB,
      the observed variations in treatment intervention and survival outcomes may
      represent a target for further research.

PMID- 29204527
TI  - Outcomes and toxicity of 313 prostate cancer patients receiving helical
      tomotherapy after radical prostatectomy.
AB  - Purpose: There are limited long-term data on patients treated with image guided
      intensity modulated radiation therapy (IG-IMRT) for prostate cancer recurrence or
      high-risk disease features after radical prostatectomy. We report single
      institution results for patients treated with IG-IMRT and identify variables
      associated with outcome. Methods and materials: This is a retrospective chart
      review consisting of 313 consecutive patients who were treated with adjuvant or
      salvage IG-IMRT from 2004 to 2013. Cox proportional hazards analysis was used to
      identify factors related to survival and toxicity. Toxicity was graded using the
      Common Terminology Criteria for Adverse Events Version 4.0. Results: The median
      follow-up was 55 months (range, 6-131 months). The median pre-radiation therapy
      (RT) prostate-specific antigen (PSA) was 0.3 ng/mL (range, <0.01-55.4). The vast
      majority of patients (87%) received elective pelvic nodal irradiation (median
      dose: 45 Gy). Androgen deprivation therapy (ADT) was given to 39% of patients for
      a median of 9 months. Five-year biochemical progression-free survival and distant
      metastasis-free survival were 59% (95% confidence interval, 53%-66%) and 89% (95%
      confidence interval, 85%-93%), respectively. On multivariate analysis, higher pre
      RT PSA (>0.2 ng/mL), biopsy Gleason score (>=7 [4+3]), and duration of ADT (>6
      months) were significantly associated (P < .05) with biochemical progression-free
      survival. Actuarial late grade 3 genitourinary and gastrointestinal toxicities at
      5 years were 10% and 2%, respectively. Conclusion: Our results suggest that lower
      pre-RT PSA level and longer duration of ADT are associated with improved
      biochemical control. The incidence of late grade 3 gastrointestinal toxicity was
      low, but late grade 3 genitourinary toxicity was higher than anticipated.

PMID- 29204528
TI  - Serum testosterone changes in patients treated with radiation therapy alone for
      prostate cancer on NRG oncology RTOG 9408.
AB  - Objectives: We reviewed testosterone changes for patients who were treated with
      radiation therapy (RT) alone on NRG oncology RTOG 9408. Methods and materials:
      Patients (T1b-T2b, prostate-specific antigen <20 ng/mL) were randomized between
      RT alone and RT plus 4 months of androgen ablation. Serum testosterone (ST)
      levels were investigated at enrollment, RT completion, and the first follow-up 3
      months after RT. The Wilcoxon signed rank test was used to compare pre- and post
      treatment ST levels in patients who were randomized to the RT-alone arm. Results:
      Of 2028 patients enrolled, 992 patients were randomized to receive RT alone and
      917 (92.4%) had baseline ST values available and completed RT. Of these 917
      patients, immediate and 3-month post-RT testosterone levels were available for
      447 and 373 patients, respectively. Excluding 2 patients who received hormonal
      therapy off protocol after RT, 447 and 371 patients, respectively, were analyzed.
      For all patients, the median change in ST values at completion of RT and at 3
      month follow-up were -30.0 ng/dL (p5-p95; -270.0 to 162.0; P < .001) and -34.0
      ng/dL (p5-p95, -228.0 to 160.0; P < .01), respectively. Conclusion: RT for
      prostate cancer was associated with a median 9.2% decline in ST at completion of
      RT and a median 9.3% decline 3 months after RT. These changes were statistically
      significant.

PMID- 29204529
TI  - Late small bowel toxicity after aggressive abdominopelvic intensity modulated
      radiation therapy.
AB  - Purpose: We retrospectively analyzed late small bowel toxicity in patients who
      received abdominal or pelvic intensity modulated radiation therapy (IMRT) to the
      small bowel with a maximum dose greater than the generally accepted maximal
      tolerable dose of 45 Gy. Methods and materials: All patients (N = 94) who
      received IMRT with a point dose of at least 45 Gy to tightly contoured small
      bowel between 2005 and 2014 at our institution were included. The median
      prescribed treatment dose was 70.2 Gy. The median follow-up was 20.1 months. Late
      small bowel toxicity was assessed using the Common Terminology Criteria for
      Adverse Events Version 3.0. Dosimetric variables and clinical factors were
      assessed for their relationship to small bowel toxicity. Results: The median
      maximal small bowel point dose (Dmax) was 6546.5 cGy. The estimated 5-year rates
      of freedom from at least grade 1, at least grade 2, and at least grade 3 late
      small bowel toxicity were 72.4% (95% confidence interval [CI], 60.7%-86.5%),
      91.9% (95% CI, 84.1%-100%), and 93.6% (95% CI, 86.2%-100%), respectively. One
      patient (1.1%) developed grade 3 late toxicity, and 2 patients (2.1%) developed
      grade 4 late toxicity. Use of capecitabine/5-fluorouracil treatment was a
      significant predictor (P < 0.001) of at least grade 1 and at least grade 2 small
      bowel toxicity. No other clinical factors were associated with toxicity. None of
      the dose-volume parameters were significant predictors of small bowel toxicity.
      Conclusion: It may be possible with IMRT to deliver high doses to small volumes
      of small bowel with low rates of significant long-term complications. Further
      studies should explore tolerable dose-volume relationships in cases in which
      aggressive abdominal or pelvic treatment may be warranted to treat the underlying
      malignancy.

PMID- 29204530
TI  - Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores
      after brain irradiation.
AB  - Purpose: Radiation-induced cognitive decline is relatively common after treatment
      for primary and metastatic brain tumors; however, identifying dosimetric
      parameters that are predictive of radiation-induced cognitive decline is
      difficult due to the heterogeneity of patient characteristics. The memory
      function is especially susceptible to radiation effects after treatment. The
      objective of this study is to correlate volumetric radiation doses received by
      critical neuroanatomic structures to post-radiation therapy (RT) memory
      impairment. Methods and materials: Between 2008 and 2011, 53 patients with
      primary brain malignancies were treated with conventionally fractionated RT in
      prospectively accrued clinical trials performed at our institution. Dose-volume
      histogram analysis was performed for the hippocampus, parahippocampus, amygdala,
      and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at
      least 6 months after RT. Impairment was defined as an immediate recall score
      <=15. For each anatomic region, serial regression was performed to correlate
      volume receiving a given dose (VD(Gy)) with memory impairment. Results:
      Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment
      (P < .05). Within this range, the hippocampal V55Gy was the most significant
      predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with
      tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%
      28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%),
      respectively. Conclusions: The hippocampal V55Gy is a significant predictor for
      impairment, and a limiting dose below 55 Gy may minimize radiation-induced
      cognitive impairment.

PMID- 29204531
TI  - Axillary lymph node coverage with 3-dimensional tangential field irradiation and
      correlation with heart and lung dose.
AB  - Purpose: The American College of Surgeons Oncology Group Z0011 trial indicated no
      benefit from axillary lymph node (LN) dissection after a positive sentinel LN
      biopsy in patients receiving breast irradiation, suggesting that level I-II LNs
      were covered in tangential fields. Methods and materials: We evaluated 50
      computed tomography-based tangential breast plans and contoured level I-III
      axillary LNs using the Radiation Therapy Oncology Group guidelines. The volumes
      of level I-III LN regions covered by 90% and 95% of the prescription dose (PD)
      were calculated and correlated with the V20 ipsilateral lung and mean heart dose.
      We calculated field length, distance from the humeral head, and separation. The
      Pearson correlation method and linear models were used in the correlative study.
      Results: Level I LN mean and median volume (MMV) covered by 90% of the PD were
      46.8% and 47.2%, respectively. MMV covered by 95% of the PD was 30.8% and 29.62%.
      Mean and median dose to level I LNs were 29.03 Gy and 30.13 Gy, respectively. The
      MMV of level II LNs covered by 90% of the PD was 2.49% and 0%. The mean and
      median dose to level II LNs were 6.09 Gy and 2.12 Gy, respectively. The MMV of
      level III LNs was 0% with a mean and median dose of 1.04 Gy and 0.92 Gy,
      respectively. There was a moderate correlation between the 95% prescription
      coverage of level I LNs and V20 ipsilateral lung and a smaller correlation
      between 95% prescription coverage of level I LNs and mean heart dose. Distance
      from the humeral head was inversely correlated with coverage of level I and II
      LNs and positively correlated with V20 lung. Conclusion: In most patients, <50%
      of the level I LN volume was covered by 90% of the PD and <30% was covered by
      95%; <5% of the level II nodes were covered by 90% of the PD; and coverage was 0%
      for level III LNs.

PMID- 29204532
TI  - Foreword.

PMID- 29204533
TI  - An undertaking of legacy and innovation.

PMID- 29204534
TI  - Retrospective evaluation of frozen section use for thyroid nodules with a prior
      fine needle aspiration diagnosis of Bethesda II-VI: The Weill Cornell Medical
      College experience.
AB  - Objective: To evaluate the Weill Cornell Medical College (WCMC)/New York
      Presbyterian Hospital (NYPH) experience with intraoperative frozen (IOF) section
      in the management of thyroid nodules with a fine needle aspiration (FNA)
      diagnosis of Bethesda II-VI and to analyze the cost and pathology benefit it
      provides. Methods: The surgical and cytopathology files at WCMC/NYPH were
      searched within the time period of January 2008 to May 2013. A total of 435
      thyroid specimens were identified for which both an FNA and subsequent IOF
      section was performed. The FNA was correlated with the locations of the resected
      nodule and the nodule frozen for intraoperative diagnosis. The results of the FNA
      were compared to the IOF section diagnosis and final diagnosis (FD). Results:
      Among 435 cases, the FNA diagnosis was Bethesda II: 149 cases, Bethesda III: 170
      cases, Bethesda IV: 91 cases, Bethesda V: 19 cases, and Bethesda VI: 6 cases.
      There were a total of 83 carcinomas identified on FD, which included 69 papillary
      thyroid carcinomas (PTCs), 12 follicular carcinomas, and 2 poorly differentiated
      carcinomas. The preoperative FNA diagnosis for these carcinomas was as follows:
      Bethesda II, 11/149 (7.4%), Bethesda III, 24/170 (14%), Bethesda IV, 26/91 (29%),
      Bethesda V, 16/19 (84%), and Bethesda VI, 6/6 (100%). IOF section contributed to
      the diagnosis of malignancy in 16/429 (4%) cases: 1/149 (0.7%) Bethesda II, 5/170
      (3%) Bethesda III, 2/91 (1.1%) Bethesda IV, and 8/19 (42%) Bethesda V. The
      diagnosis of malignancy was confirmed in the 6 Bethesda VI cases by IOF section.
      There were no false positives on IOF section. IOF had a sensitivity and
      specificity of 26% and 100%, respectively. Conclusion: The role of IOF section is
      limited in the evaluation of thyroid nodules. IOF section is most useful for
      nodules with an FNA diagnosis of Bethesda V lesions. The diagnosis of follicular
      variant of PTC remains difficult on frozen section.

PMID- 29204535
TI  - Bypassing the blood-brian barrier using established skull base reconstruction
      techniques.
AB  - Background: Neurological disorders represent a profound healthcare problem
      accounting for 6.3% of the global disease burden. Alzheimer's disease alone is
      expected to impact over 115 million people worldwide by 2050 with a cost of over
      $1 trillion per year to the U.S. economy. Despite considerable advances in our
      understanding of the pathogenesis and natural history of neurological disorders,
      the development of disease modifying therapies have failed to keep pace. This
      lack of effective treatments is directly attributable to the presence of the
      blood-brain and blood-cerebrospinal fluid barriers (BBB and BCSFB) which prevent
      up to 98% of all potential neuropharmaceutical agents from reaching the central
      nervous system (CNS). These obstacles have thereby severely limited research and
      development into novel therapeutic strategies for neurological disease. Current
      experimental methods to bypass the BBB, including pharmacologic modification and
      direct transcranial catheter implantation, are expensive, are associated with
      significant complications, and cannot be feasibly scaled up to meet the chronic
      needs of a large, aging patient population. Transmucosal drug delivery: An
      innovative method of direct CNS drug delivery using heterotopic mucosal grafts
      was described. This method is based on established endoscopic skull base
      nasoseptal flap reconstruction techniques. The model has successfully
      demonstrated CNS delivery of chromophore-tagged molecules 1000 times larger than
      those typically permitted by the BBB. Conclusions: This innovative technique
      represents the first described method of permanently bypassing the blood-brain
      barrier using purely autologous tissues. This has the potential to dramatically
      improve the current treatment of neurological disease by providing a safe and
      chronic transnasaldelivery pathway for high molecular weight
      neuropharmaceuticals.

PMID- 29204537
TI  - Olfactory dysfunction and its measurement in the clinic.
AB  - The sense of smell is largely taken for granted by laypersons and medical
      professionals alike. Indeed, its role in determining the flavor of foods and
      beverages, as well as in warning of, or protecting against, environmental
      hazards, often goes unrecognized. This is exemplified, in part, by the fact that
      most patients presenting to medical clinics with "taste" problems are typically
      subjected to complex brain imaging and gastroenterological tests without the
      sense of smell even being tested or considered as a basis of the problem. Aside
      from frank deficiencies in sweet, sour, bitter, salty and savory (umami)
      sensations, "taste" disorders most commonly reflect inadequate stimulation of the
      olfactory receptors via the retronasal route; i.e., from volatiles passing to the
      receptors from the oral cavity through the nasal pharynx. This article describes
      the two most common procedures for measuring the sense of smell in the clinic and
      provides examples of the application of these tests to diseases and other
      disorders frequently associated with smell loss. Basic issues related to
      olfactory testing and evaluation are addressed. It is pointed out that smell
      loss, particularly in later life, can be a harbinger for not only a range of
      neurodegenerative diseases, but can be a prognostic indicator of early mortality.

PMID- 29204536
TI  - Clinical consequences and economic costs of untreated obstructive sleep apnea
      syndrome.
AB  - Objective: To provide an overview of the healthcare and societal consequences and
      costs of untreated obstructive sleep apnea syndrome. Data sources: PubMed
      database for English-language studies with no start date restrictions and with an
      end date of September 2014. Methods: A comprehensive literature review was
      performed to identify all studies that discussed the physiologic, clinical and
      societal consequences of obstructive sleep apnea syndrome as well as the costs
      associated with these consequences. There were 106 studies that formed the basis
      of this analysis. Conclusions: Undiagnosed and untreated obstructive sleep apnea
      syndrome can lead to abnormal physiology that can have serious implications
      including increased cardiovascular disease, stroke, metabolic disease, excessive
      daytime sleepiness, work-place errors, traffic accidents and death. These
      consequences result in significant economic burden. Both, the health and societal
      consequences and their costs can be decreased with identification and treatment
      of sleep apnea. Implications for practice: Treatment of obstructive sleep apnea
      syndrome, despite its consequences, is limited by lack of diagnosis, poor patient
      acceptance, lack of access to effective therapies, and lack of a variety of
      effective therapies. Newer modes of therapy that are effective, cost efficient
      and more accepted by patients need to be developed.

PMID- 29204539
TI  - Applied anatomy of the submental island flap and its clinical application in the
      repair of defects following hypopharyngeal carcinoma resection.
AB  - Objective: To explore the feasibility of the submental island flap in the repair
      of hypopharyngeal defects. Methods: We collected wet specimens of fresh cadaveric
      heads from the Han Chinese adult population for applied anatomy of the submental
      island flap, and followed five patients with pyriform sinus carcinoma after
      reconstruction surgery using submental island flaps. Results: We found that the
      average length and width of the submental island flaps were (65.20 +/- 11.69) mm
      and (46.70 +/- 6.59) mm, respectively. The skin flap in all five patients
      survived after surgery, and tracheal tubes and gastric tubes were removed 7-36
      days after surgery. Patients were followed up for 24-42 months, pharyngeal flaps
      grew well, and speech and swallowing functions were satisfactory. Conclusion: The
      submental island flap is a preferred material for the repair of hypopharyngeal
      defects after hypopharyngeal carcinoma resection, because of good blood supply,
      easy harvesting, and high survival rate.

PMID- 29204538
TI  - Salvage surgery for nasopharyngeal cancer.
AB  - Nasopharyngeal carcinoma (NPC) is a special type of head and neck cancer with a
      widely variable geographical variation in incidence. The central location of the
      tumor inside the head coupled with the radiosensitivity of the tumor to radiation
      made radiation therapy the first choice in primary treatment of NPC. Advances in
      radiotherapy and chemotherapy have markedly improved the local control of NPC.
      Unfortunately, a small but significant number of patients still suffered from
      loco-regional failures that would be amenable to re-treatment. Traditional form
      of retreatment was to employ a second course of radiation. The efficacy of re
      irradiation to treat local of regional recurrent NPC has been suboptimal.
      Moreover, the local tissue had already received a high dose of radiation and the
      second radiation could result in radiation toxicities to the local tissue,
      leading to significant complications. Surgical salvage, on the other hand, could
      spare the patients from complications of re-treatment. Due to the difficult
      access of the nasopharynx, various surgical approaches had been devised for
      nasopharyngectomy. The maxillary swing approach had the largest published
      experience with over 300 cases from various centers. In the recent decade, the
      endoscopic approach with or without robotic assistance had gained popularity for
      resecting small, centrally located recurrences. This minimally invasive approach
      further reduced the morbidity for treating locally recurrent NPC. Nodal
      recurrences had been a rare entity after the introduction of modern radiotherapy
      technique and concurrent chemotherapy. Treatment of nodal failure with second
      radiation has dismal results. Surgical removal of the lymph node harboring the
      recurrence should be in the form of a formal radical neck dissection. In cases of
      extensive nodal recurrence where microscopic disease may be present after a
      formal neck dissection, additional radiotherapy can be delivered with after
      loading brachytherapy. Surgical treatment played a definitive role in salvage of
      loco-regional failures of nasopharyngeal carcinoma.

PMID- 29204540
TI  - Clinicopathological significance of p16, cyclin D1, Rb and MIB-1 levels in skull
      base chordoma and chondrosarcoma.
AB  - Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor
      suppressor protein (Rb) and MIB-1 in skull base chordoma and chondrosarcoma
      tissues, and to determine the clinicopathological significance of the above
      indexes in these diseases. Methods: A total of 100 skull base chordoma, 30
      chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by
      immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1
      proteins were assessed for potential correlation with the clinicopathological
      features. Results: As compared to normal cartilage specimen (control), there was
      decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1
      proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI
      levels were significantly increased in skull base chordoma specimens with
      negative expression of p16, and positive expression of cyclin D1 and Rb (P <
      0.05). Significantly elevated MIB-1 LI was also detected in skull base
      chondrosarcoma tissues, while there was negative expression of p16, cyclin D1 and
      Rb (P < 0.05). In skull base chordoma, p16 negatively correlated with cyclin D1
      and Rb, while cyclin D1 positively correlated with Rb. Additionally, p16, cyclin
      D1, Rb, or MIB-1 expression showed no correlation with age, gender, or
      pathological classification of patients with skull base chordoma (P > 0.05).
      However, p16 and MIB-1 levels correlated with the intradural invasion, and
      expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P <
      0.05). Further, the expression of p16 and MIB-1 appeared to correlate with the
      prognosis of patients with skull base chordoma. Conclusions: The abnormal
      expression of p16, cyclin D1 and Rb proteins might be associated with the
      tumorigenesis of skull base chordoma and chondrosarcoma.

PMID- 29204541
TI  - A 3D benign paroxysmal positional vertigo model for study of otolith disease.
AB  - Objective: To develop a three-dimensional study tool of the membranous labyrinth
      in order to study the pathophysiology, diagnostic workup and treatment of benign
      paroxysmal positional vertigo (BPPV). BPPV is the most common cause of peripheral
      vertigo. Its diagnosis and treatment depend on an understanding of the anatomy of
      the vestibular labyrinth and its position relative to the head. To date, many
      illustrations have been made to explain principals of diagnosis and treatment of
      BPPV, but few have been based on anatomical studies of the membranous labyrinth.
      Methods: A cadaveric human membranous labyrinth was axially sectioned at 20 MUm
      resolution, stained and segmented to create a high-resolution digital model. The
      model was cloned to create an enantiomeric pair of labyrinths. These were
      associated a 3D model of a human skull, segmented from MRI data, and were
      oriented according to established anatomic norms. Canal markers representing
      otoliths were created to mark canalith position during movement of the model
      within the 3D environment. Results: The model allows visualization of true
      membranous labyrinth anatomy in both ears simultaneously. The dependent portion
      of each semicircular duct and of the utricle can easily be visualized in any head
      position. Moveable markers can mark the expected progress of otolith debris with
      changes in head position and images can be captured to document simulations. The
      model can be used to simulate pathology as well as diagnostic maneuvers and
      treatment procedures used for BPPV. The model has great potential as a teaching
      tool. Conclusion: A simple model based on human anatomy has been created to allow
      careful study of BPPV pathophysiology and treatment. Going forward, this tool
      could offer insights that may lead to more accurate diagnosis and treatment of
      BPPV.

PMID- 29204542
TI  - The role of serial physical examinations in the management of angioedema
      involving the head and neck: A prospective observational study.
AB  - Objective: To elucidate the progression of angioedema of the head and neck with
      routine management and to assess the utility of serial physical exams and
      fiberoptic laryngoscopy in its management. Methods: This study was a prospective
      observational research. From 2013 to 2014, a prospective observational study was
      conducted at a tertiary referral center. Forty patient were approached, 7
      refused, 33 (18-90 years old) were enrolled. Patients presented with angioedema
      involving the head and neck over a 12 month period were asked to participate in
      the study. Physical examination and fiberoptic laryngoscopy were performed at
      presentation and then repeated at least 1 h later. Results: Thirty-three patients
      with head and neck angioedema from any cause were enrolled (mean age 58, range 23
      89 years). The upper lip was the most commonly involved site (58%). On
      reevaluation, 82% of patients reported subjective improvement in symptoms. The
      association between subjective improvement and the physical exam, including
      fiberoptic laryngoscopy findings, was statistically significant (P < 0.001).
      Conclusion: In stable patients with angioedema of any head and neck subsite, self
      reported symptoms are associated with clinical stability or improvement as
      assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be
      an appropriate surrogate to monitor clinical status without the need for routine
      serial physical examinations or fiberoptic laryngoscopy, though further study is
      needed.

PMID- 29204543
TI  - Assessment of complications due to intratympanic injections.
AB  - Objective: The purpose of the study is to report and to analyze the complications
      following intratympanic injections (ITI) of steroids. The occurrence rate of
      complications at different ITI sites, four quadrants of eardrum, was also
      compared. Methods: A retrospective clinical review in a medical center. Each
      patient received ITI twice in a week for 2-3 consecutive weeks as a salvage
      therapy for sudden sensorineural hearing loss. Post-injection complications,
      especially transient dizziness and vertigo, were recorded. Patients with acute or
      chronic vertigo episodes in 1 month were excluded. Results: A total of 59
      patients with sudden sensorineural hearing loss and a total of 278 times of ITI
      were performed in 1 year. The post-injection complications included pain, tongue
      numbness, transient dizziness, vertigo, tinnitus, and a small persistent
      perforation. There was no significant difference in the occurrence of these
      complications between the injections sites on the 4 quadrants of the tympanic
      membrane. However, there was statistical significance in the post-injection
      vertiginous episode after IT injections to posterior-inferior quadrant (Q3) and
      posterior-superior quadrant (Q4) compared to anterior-superior quadrant (Q1) and
      anterior-inferior quadrant (Q2) (P = 0.0113). Conclusion: IT injection is
      recommended to be applied to the Q2 since the Q1 and Q4 injections are more
      likely to induce the adverse effect of tongue numbness, while the Q3 and Q4 areas
      are more likely to induce post-injection vertigo.

PMID- 29204544
TI  - Clinicopathological study of surgical margins in squamous cell carcinoma of
      buccal mucosa.
AB  - Objective: To evaluate the margins of resected specimen of oral squamous cell
      carcinoma (SCC) and to document the surgical margin (measured at the time of
      resection) and margins at the time of pathological examination (after immersion
      of the specimen in formalin). Methods: Patients who were diagnosed and confirmed
      with squamous carcinoma of buccal mucosa were included in the study. Patients
      underwent resection of the tumor with a margin of 1 cm. Soon after resection, the
      distance between outermost visible margin of the tumor and the margin of the
      specimen was measured and documented. Specimens were fixed in 10% formalin and
      submitted for gross and histopathological examination. The closest
      histopathologic margin was compared with the in situ margin (10 mm) to determine
      and document any shrinkage of the margin and the percentage of discrepancy if
      any. Results: A total of 52 specimens were collected from patients between
      January 2014 and December 2014. All specimens were obtained from the oral cavity
      (n = 52) of which 43 (82.7%) were squamous cell carcinoma and 9 (17.3%) were
      verrucous variant of squamous cell carcinoma. The average decrease in tumor
      margins measured after fixation in formalin was found to be statistically
      significant (P < 0.05) in 65% of cases. Conclusion: Tumor margin shrinks
      significantly after formalin fixation by about 25%. The operating surgeon and
      pathologist should be well aware of such changes while planning for further
      management thereby ensuring adequate margin of resection and adjuvant treatment
      wherever required to prevent possible local recurrence of the disease.

PMID- 29204545
TI  - Normal values of nasal NO and exhaled NO in young Chinese people aged 9 - 22
      years.
AB  - Objective: To assess the normal levels of nasal nitric oxide (NNO) and fractional
      exhaled nitric oxide (FENO) in healthy Chinese young people, and to determine
      whether the obtained values were associated with age, sex, height, weight, BMI
      (body mass index) or BSA (body surface area). Methods: One hundred and twenty
      healthy people were selected from a total of 436 Chinese young people based on
      their answers to a questionnaire. An electrochemical analyzer (NIOX MINO system)
      was used to measure NNO and FENO. The relationship between NNO, FENO and age,
      sex, height, weight, BMI, BSA was analyzed using SPSS software. Results: The
      values of NNO were normal distributed (mean 273.5 ppb; SD 112.3). The values of
      FENO were non-normally (Skewed) distributed (median: 14.00 ppb; interquartile
      range: 7.00 ppb). The obtained NNO values were independent of age, sex, height,
      weight, BMI and BSA, but were positively correlated to lnFENO (FENO log base e);
      lnFENO values were also independent of age, height, weight, BMI and BSA, but
      correlated with NNO and sex. Conclusions: NNO values positively correlate with
      lnFENO in healthy people and the levels of each may be predicted by the other.
      The results of this study are expected to serve as a reference for future studies
      in China.

PMID- 29204546
TI  - Value within otolaryngology: Assessment of the cost-utility analysis literature.
AB  - Objective: To assess the characteristics and quality of cost utility analyses
      (CUA) related to otolaryngology within the CEA registry and to summarize their
      collective results. Methods: All cost-utility analyses published between 1976 and
      2011 contained in the Cost-Effectiveness Analysis Registry (CEA Registry) were
      evaluated. Topics that fall within the care of an otolaryngologist were included
      in the review regardless of the presence of an otolaryngologist author. Potential
      associations between various study characteristics and CEA registry quality
      scores were evaluated using the Pearson product moment correlation coefficient.
      Results: Sixty-one of 2913 (2.1%) total CUA publications screened were related to
      otolaryngology. Eighteen of 61 (29.5%) publications included an otolaryngologist
      as an author. Fourteen studies agreed on the cost effectiveness of at least
      unilateral cochlear implantation and six of seven (85.7%) studies demonstrated
      the cost effectiveness of continuous positive airway pressure (CPAP) for
      obstructive sleep apnea (OSA). Forty-six percent (28 of 61) of all manuscripts
      were published between 2008 and 2011. A more recent publication year was
      associated with a higher CEA registry quality score while the presence of an
      otolaryngologist author and journal impact factor had no significant correlation
      with the quality of the CUA. Conclusion: Based on current evidence in the CEA
      registry, unilateral cochlear implantation for hearing loss and CPAP for OSA are
      both cost-effective therapeutic interventions. Although CUAs in otolaryngology
      have increased in quantity and improved in quality in more recent years, there is
      a relative lack of CUAs in otolaryngology in comparison to other subspecialties.

PMID- 29204547
TI  - Evolution of the rhytidectomy.
AB  - Since the advent of facelift surgery, there has been a progressive evolution in
      technique. Methods of dissection trended towards progressively aggressive surgery
      with deeper dissection for repositioning of ptotic facial tissues. In recent
      decades, the pendulum has swung towards more minimally invasive options.
      Likewise, there has been a shift in focus from repositioning alone to the
      addition of volumization for facial rejuvenation. The techniques in this article
      are reviewed in a chronologic fashion with a focus on historical development as
      well as brief discussion on efficacy in relation to the other existing options.
      There is currently no gold standard technique with a plethora of options with
      comparable efficacy. There is controversy over which approach is optimal and
      future research is needed to better delineate optimal treatment options, which
      may vary based on the patient.

PMID- 29204548
TI  - Overview of smartphone applications for sleep analysis.
AB  - Objective: To review and assess the current selection of sleep analysis
      smartphone applications (apps) available for download. Methods: The iOS and
      Google Play mobile app store were searched for sleep analysis apps targeted for
      consumer use. Alarm clock, sleep-aid, snoring and sleep-talking recorder, fitness
      tracker apps, and apps geared towards health professionals were excluded. App
      information and features were obtained from in-store descriptions, and the app
      developer website. Results: A total of 51 unique sleep apps in both iOS and
      Google Play stores were included. The apps were rated 3.8/5 in both stores, and
      had an average price of $1.12 in the iOS store and $0.58 in the Google Play
      store. >65% of sleep apps report on sleep structure, including duration, time
      awake, and time in light/deep sleep, while reporting of REM was limited. The
      availability of extra features was variable, ranging from 4% to 73% of apps.
      Conclusions: There are a variety of sleep analysis apps with a range of
      functionality. The apps with the most reviews from the each store are featured.
      Many apps provide data on sleep structure; however the algorithms are not
      validated by scientific literature or studies. Since patients may inquire about
      their sleep habits from these apps, it is necessary for physicians to be aware of
      the most common apps and the features offered and their limitations in order to
      properly counsel patients.

PMID- 29204549
TI  - Novel therapeutics and emerging technologies in head and neck cancer.

PMID- 29204550
TI  - Novel p53 therapies for head and neck cancer.
AB  - Inactivation of the tumor suppressor p53 is the predominant pathogenetic event in
      head and neck squamous cell carcinoma (HNSCC). The p53 pathway in HNSCC can be
      compromised through multiple mechanisms including gene mutations, hyperactivation
      of endogenous negative p53 regulators and by the human papillomavirus E6 protein.
      Inactivation of p53 is associated with poor clinical response and outcome;
      therefore, restoration of the p53 signaling cascade may be an effective approach
      to ablate HNSCC cells. Viral approaches to restore p53 activity in HNSCC have
      been well-studied and shown modest activity in clinical trials. Recent work has
      focused on high-throughput screens and rational designs to identify and develop
      small molecules to rescue p53 function. Several p53-targeting small molecules
      have demonstrated very promising activity in pre-clinical studies but have yet
      progressed to the clinical setting. Further development of p53 therapies, in
      particular chemical approaches, should be prioritized and evaluated in the HNSCC
      setting.

PMID- 29204551
TI  - mTOR, metabolism, and the immune response in HPV-positive head and neck squamous
      cell cancer.
AB  - Extensive preclinical studies have identified mammalian target of rapamycin
      (mTOR) activation as a frequent molecular signature underlying head and neck
      squamous cell carcinoma (HNSCC), including the distinct clinical subtype that is
      human papillomavirus (HPV) related, and have demonstrated the potential
      therapeutic utility of mTOR inhibitors in the treatment of these cancers.
      Numerous clinical studies have begun to evaluate this potential, however few have
      selected for and fewer have focused specifically on HPV-related disease. While
      HPV-positive (HPV+) HNSCC patients have a generally favorable prognosis, the
      overall number of patients who suffer failed treatment, recurrent disease,
      metastasis, and death is increasing due to the rapidly increasing incidence of
      HPV-related cancers. In this review, we discuss the rationale for proposing the
      adjuvant use of mTOR inhibition in the treatment of HPV+ HNSCC, highlighting the
      interplay of virally activated mTOR signaling, cellular metabolism, and the anti
      tumor immune response.

PMID- 29204552
TI  - The current status of oncolytic viral therapy for head and neck cancer.
AB  - Objective: Cancer affects the head and neck region frequently and leads to
      significant morbidity and mortality. Oncolytic viral therapy has the potential to
      make a big impact in cancers that affect the head and neck. We intend to review
      the current state of oncolytic viruses in the treatment of cancers that affect
      the head and neck region. Method: Data sources are from National clinical trials
      database, literature, and current research. Results: There are many past and
      active trials for oncolytic viruses that show promise for treating cancers of the
      head and neck. The first oncolytic virus was approved by the FDA October 2015 (T
      VEC, Amgen) for the treatment of melanoma. Active translational research
      continues for this and many other oncolytic viruses. Conclusion: The evolving
      field of oncolytic viruses is impacting the treatment of head and neck cancer and
      further trials and agents are moving forward in the coming years.

PMID- 29204553
TI  - Interleukin-6 role in head and neck squamous cell carcinoma progression.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine which plays an important role in a
      number of cellular processes including proliferation, survival, differentiation,
      migration and invasion. IL-6 mediates its downstream effects by activating a
      number of signaling cascades including JAK/STAT, PI3K/AKT and MAPK pathways. In
      addition to its effects on tumor cells, IL-6 also regulates tumor progression and
      tumor metastasis by modulating tumor angiogenesis and tumor lymphangiogenesis. A
      number of studies have shown that IL-6 levels are markedly upregulated in cancer
      patients. We and others have shown that high IL-6 expression independently
      predicts tumor recurrence, tumor metastasis and poor survival in head and neck
      cancer patients. Therefore targeting IL-6 signaling is a potential therapeutic
      strategy for the treatment of head and neck squamous cell carcinoma (HNSCC). In
      this review, we discuss the current understanding of the role of IL-6 in HNSCC
      progression and potential therapeutic strategies to target IL-6 signaling for the
      treatment of head and neck cancer patients.

PMID- 29204554
TI  - Advancing theranostics with tumor-targeting peptides for precision
      otolaryngology.
AB  - Worldwide, about 600,000 head and neck squamous cell carcinoma (HNSCC) are
      detected annually, many of which involve high risk human papilloma virus (HPV).
      Surgery is the primary and desired first treatment option. Following surgery, the
      existence of cancer cells at the surgical margin is strongly associated with
      eventual recurrence of cancer and a poor outcome. Despite improved surgical
      methods (robotics, microsurgery, endoscopic/laparoscopic, and external imaging),
      surgeons rely only on their vision and touch to locate tumors during surgery.
      Diagnostic imaging systems like computed tomography (CT), magnetic resonance
      imaging (MRI), single-photon emission computed tomography (SPECT) and positron
      emission tomography (PET) are too large, slow and costly to use efficiently
      during most surgeries and, ultrasound imaging, while fast and portable, is not
      cancer specific. This purpose of this article is to review the fundamental
      technologies that will radically advance Precision Otolaryngology practices to
      the benefit of patients with HNSCC. In particular, this article will address the
      potential for tumor-targeting peptides to enable more precise diagnostic imaging
      while simultaneously advancing new therapeutic paradigms for next generation
      image-guided surgery, tumor-specific chemotherapeutic delivery and tumor
      selective targeted radiotherapy (i.e., theranostic).

PMID- 29204555
TI  - Circulating tumor cells in head and neck cancer: A review.
AB  - Carcinoma of the head and neck represents 3.5% of all cancers, and the vast
      majority of these tumors are squamous cell carcinoma (HNSCC). With a stable
      overall survival rate of 50% among all stages, there is continued interested in
      developing measures for early detection and disease aggressiveness. Circulating
      tumor cells (CTCs) have been identified as a potential marker for early
      metastatic disease, response to treatment, and surveillance in head and neck
      squamous cell carcinoma. In this article, techniques of CTC detection,
      applications of CTC technology, and outcomes of HNSCC patients will be discussed.

PMID- 29204556
TI  - Contemporary use of sentinel lymph node biopsy in the head and neck.
AB  - Sentinel lymph node biopsy has become a well-established and commonplace practice
      in many oncologic disease sites as a means to stage the regional lymphatics,
      avoid unnecessary surgery and decrease patient morbidity. In the head and neck,
      its role is well established for cutaneous melanoma with proven fidelity and
      survival benefit. Its role in use for other sites such as oral cavity carcinoma
      continues to develop with promising results from several recent trials. Although
      not widely adopted, the potential benefits of sentinel lymph node biopsy in the
      management of oral cavity carcinoma are apparent. Refinements in technology and
      protocols including development of novel radiopharmaceutical tracers, routine
      incorporation of detailed anatomic imaging, increasing surgeon experience and
      development of new intraoperative identification aids will likely lead to
      improvements in the use and accuracy of this technique.

PMID- 29204557
TI  - Transoral robotic surgery frontiers.
AB  - Transoral robotic surgery is a exciting field that continues to develop and push
      the boundaries of current procedural ability and challenges historical treatment
      paradigms. With the first use of a surgical robot in 1985, to the first clinical
      use of the robot transorally in 2005, there was some lag in adoption of robotic
      techniques in the head and neck region. However, since 2005 transoral robotic
      surgery has rapidly gained momentum amongst head and neck surgeons. With FDA
      approval of the da Vinci robot in 2009, transoral robotic surgery is currently
      offered as a treatment modality for malignant and nonmalignant disease of the
      head and neck region. This new technology is being used to reconsider historical
      treatment paradigms for malignancies of the upper aerodigestive tract due to the
      fact that minimally invasive surgical access to the oropharynx and larynx has
      been improved. Along with this enhanced access have come innovative procedures
      and uses of the technology for multiple facets of head and neck disease.
      Technology continues to improve and innovation in surgical robotics is expected
      to continue as more companies attempt to capture this market. This article aims
      to provide a view at the landscape of transoral robotic surgery and explore the
      future frontiers.

PMID- 29204558
TI  - High risk cutaneous squamous cell carcinoma of the head and neck.
AB  - The majority of patients with head and neck cutaneous squamous cell carcinoma
      (cSCC) are successfully treated with surgical treatment of the primary site.
      While only a minority of patients is at risk for regional metastasis, these
      patients have significantly worse outcomes. Tumor and patient factors that place
      patients at high risk for development of regional metastasis have been
      identified. Advancing treatment of cSCC requires identifying and escalating
      treatment in this high risk patient population, while avoiding overtreatment of
      the majority of cSCC patients that do not develop regional metastasis. Sentinel
      lymph node biopsy has emerged as a promising technique in cSCC to detect
      micrometastasis and allow early surgical treatment of regional disease. Future
      directions involve genomic characterization of metastatic and nonmetastatic cSCC
      to identify genomic alterations causing metastasis that may be used to predict
      disease behavior.

PMID- 29204559
TI  - The impact of round window vs cochleostomy surgical approaches on interscalar
      excursions in the cochlea: Preliminary results from a flat-panel computed
      tomography study.
AB  - Objective: To evaluate incidence of interscalar excursions between round window
      (RW) and cochleostomy approaches for cochlear implant (CI) insertion. Methods:
      This was a retrospective case-comparison. Flat-panel CT (FPCT) scans for 8 CI
      users with Med-El standard length electrode arrays were collected. Surgical
      technique was identified by a combination of operative notes and FPCT imaging.
      Four cochleae underwent round window insertion and 4 cochleae underwent
      cochleostomy approaches anterior and inferior to the round window. Results: In
      our pilot study, cochleostomy approaches were associated with a higher likelihood
      of interscalar excursion. Within the cochleostomy group, we found 29% of
      electrode contacts (14 of 48 electrodes) to be outside the scala tympani. On the
      other hand, 8.5% of the electrode contacts (4 of 47 electrodes) in the round
      window insertion group were extra-scalar to the scala tympani. These
      displacements occurred at a mean angle of occurrence of 364 degrees  +/- 133
      degrees , near the apex of the cochlea. Round window electrode displacements tend
      to localize at angle of occurrences of 400 degrees  or greater. Cochleostomy
      electrodes occurred at an angle of occurrence of 19 degrees -490 degrees .
      Conclusions: Currently, the optimal surgical approach for standard CI electrode
      insertion is highly debated, to a certain extent due to a lack of post-operative
      assessment of intracochlear electrode contact. Based on our preliminary findings,
      cochleostomy approach is associated with an increased likelihood of interscalar
      excursions, and these findings should be further evaluated with future
      prospective studies.

PMID- 29204560
TI  - Temporal and spectral contributions to musical instrument identification and
      discrimination among cochlear implant users.
AB  - Objective: To investigate the contributions of envelope and fine-structure to the
      perception of timbre by cochlear implant (CI) users as compared to normal hearing
      (NH) listeners. Methods: This was a prospective cohort comparison study. Normal
      hearing and cochlear implant patients were tested. Three experiments were
      performed in sound field using musical notes altered to affect the characteristic
      pitch of an instrument and the acoustic envelope. Experiment 1 assessed the
      ability to identify the instrument playing each note, while experiments 2 and 3
      assessed the ability to discriminate the different stimuli. Results: Normal
      hearing subjects performed better than CI subjects in all instrument
      identification tasks, reaching statistical significance for 4 of 5 stimulus
      conditions. Within the CI population, acoustic envelope modifications did not
      significantly affect instrument identification or discrimination. With envelope
      and pitch cues removed, fine structure discrimination performance was similar
      between normal hearing and CI users for the majority of conditions, but some
      specific instrument comparisons were significantly more challenging for CI users.
      Conclusions: Cochlear implant users perform significantly worse than normal
      hearing listeners on tasks of instrument identification. However, cochlear
      implant listeners can discriminate differences in envelope and some fine
      structure components of musical instrument sounds as well as normal hearing
      listeners. The results indicated that certain fine structure cues are important
      for cochlear implant users to make discrimination judgments, and therefore may
      affect interpretation toward associating with a specific instrument for
      identification.

PMID- 29204561
TI  - Electrode selection for hearing preservation in cochlear implantation: A review
      of the evidence.
AB  - Objective: To review and assess the ideal length of electrode in cochlear implant
      patients for hearing preservation. Methods: The English language literature was
      reviewed for studies including hearing preservation and speech understanding for
      electrodes of different lengths. Results: One prospective trial was found, and
      there were no studies that randomized patients into different length electrodes
      with an intent to preserve hearing. Eight studies total included multiple length
      electrodes and contained data regarding hearing preservation. Conclusions:
      Although there is some evidence that indicates that shorter electrodes may
      improve both short and long-term hearing preservation rates in cochlear implant
      patients, no study has directly compared implant length on hearing preservation
      in a similar patient population. A randomized trial of short and standard length
      electrodes for hearing preservation is warranted. In the interim, utilization of
      current electrodes measuring 20-25 mm could seem to be a prudent approach when
      seeking to preserve residual hearing without unduly compromising cochlear
      coverage.

PMID- 29204562
TI  - Transmastoid resurfacing versus middle fossa plugging for repair of superior
      canal dehiscence: Comparison of techniques from a retrospective cohort.
AB  - Objective: To compare and contrast our experience with middle cranial fossa
      approach (MFR) and transmastoid approach with capping of the dehiscence (TMR) of
      superior semicircular canal dehiscence and to determine guidelines to help guide
      management of these patients. Methods: All patients from 2005 to 2014 with
      symptomatic superior semicircular canal dehiscence syndrome with dehiscence
      demonstrated on CT scan of the temporal bone who underwent surgical repair and
      had a minimum 3 months of follow up. Surgical repair via the MFR or TMR,
      preoperative CT temporal bone, preoperative, and postoperative cervical
      vestibular evoked myogenic potential (cVEMP) testing and anterior canal video
      head thrust testing (vHIT). Success of repair was stratified as complete success,
      moderate success, mild success, or failure based on resolution of all symptoms,
      the chief complaint, some symptoms, or no improvement, respectively. Results: A
      total of 29 ears in 27 patients underwent surgical repair of canal dehiscence.
      Complete or moderate success was seen in 71% of the MFR group compared to 80% of
      the TMR group. There were zero failures with the MFR group and no major
      intracranial complications. There were 2 failures out of 15 ears that underwent
      the TMR. Residual symptoms were most commonly vertigo or disequilibrium in the
      MFR and aural fullness or autophony in the TMR groups, respectively. MFR hospital
      stay was approximately 2 days longer. Average cVEMP threshold shifted 18 dB with
      surgical correction in the MFR group. A 29 dB average shift was seen in the TMR
      group. The MFR group had a significant reduction in their anterior canal gain
      compared to the TMR group. Conclusions: TMR is a less invasive alternative to
      MFR. However, in our series, we have not seen any intracranial complications
      (aphasia, stroke, seizures, etc.) in our MFR patients. Interestingly, vestibular
      symptoms were better addressed than audiological symptoms by the TMR suggesting
      its usefulness as a less invasive option for patients with primarily vestibular
      complaints. Residual auditory symptoms in TMR patients may be due to the flow of
      acoustic energy from the superior canal to the mastoid cavity through an
      incompletely sealed third window.

PMID- 29204563
TI  - Improvement in word recognition following treatment failure for sudden
      sensorineural hearing loss.
AB  - Objectives: Patients with sudden sensorineural hearing loss (SSNHL) may have word
      recognition scores (WRS) that correlate with pure tone average (PTA). We
      hypothesize that there is a subset of patients with SSNHL who have improved WRS
      despite stable PTA. Methods: Retrospective case review at a tertiary
      otolaryngology practice. Results: We identified 13 of 113 patients with SSNHL
      whose WRS increased despite overall stable pure tone averages. There was an
      observed average improvement in WRS by 23.8 points in this patient cohort at
      follow-up, with mean initial PTA in the affected ear at 48.7 dB. Conclusions: We
      identify a novel cohort of SSNHL patients that have failed treatment as measured
      by PTA, but who have increased WRS over time. These data have implications for
      patient counseling and lend insight into the pathophysiology of SSNHL.

PMID- 29204564
TI  - Isolated cochlear neuritis from varicella reactivation mimicking a vestibular
      schwannoma.
AB  - We present a case of a patient with progressive unilateral sensorineural hearing
      loss and tinnitus with internal auditory canal enhancement on magnetic resonance
      imaging (MRI) secondary to isolated cochlear neuritis from varicella
      reactivation. MRI following antiviral treatment showed resolution of enhancement.
      Varicella reactivation is commonly seen in the form of Ramsay Hunt syndrome,
      which is known to produce abnormal MRI enhancement from facial and
      vestibulocochlear neuritis; however, its characteristic clinical signs aid the
      diagnosis. This case is unique in that the only manifestation of varicella
      infection was unilateral hearing loss. This case outlines the importance of
      maintaining a broad differential diagnosis in the evaluation of unilateral
      hearing loss as well as recognizing the limited specificity of MRI.

PMID- 29204565
TI  - Early oral tongue cancer initially managed with surgery alone: Treatment of
      recurrence.
AB  - Objective: To report T1-2N0 tongue cancer recurrences initially treated with
      surgery alone. Methods: Between 1990 and 2010, 27 patients at tertiary hospital
      referral center institution were treated with curative intent for locoregional
      recurrence after initial glossectomy with or without neck dissection for T1-2N0
      tongue cancer. None had received adjuvant postoperative radiation as a component
      of the original treatment. Results: Median time to locoregional recurrence was 12
      months (range 5-39 months) and 78% of failures occurred in the first 2 years.
      Most treatment failures were local (63%). Salvage strategy was risk-adapted by
      individual patient. The 5-year disease specific survival (DSS) was 61%. Patients
      with local recurrences alone fared significantly better than those with regional
      recurrences (5-yr DSS: 86% vs. 22%, P = 0.0018). Local recurrences were usually
      treated by surgery alone, while regional recurrences were more commonly treated
      with combined modality treatment (P = 0.005). Conclusions: Recurrence of early
      stage oral tongue cancer can be successfully salvaged in a majority of cases.
      Patients developing regional recurrence have significantly worse prognosis than
      those with local failures.

PMID- 29204566
TI  - Dynamic swallowing study for globus patients.
AB  - Objective: To examine whether pharyngeal swallowing function is impaired in
      globus patients with swallowing difficulty by dynamic swallowing study. Methods:
      Dynamic swallowing studies were performed on 80 normal adult volunteers and 33
      globus patients with swallowing difficulty. Objective parameters such as maximum
      displacement of the hyoid bone, pharyngeal transit time, pharyngeal constriction
      ratio, and maximum opening of the esophageal entrance were measured, which were
      closely associated with the pharyngeal swallowing function in the swallowing
      process. Results: There were no significant differences between globus patients
      and normal adults in hyoid bone displacement, pharyngeal transit time, pharyngeal
      constriction ratio, or maximum opening of the esophageal entrance (p > 0.05).
      Conclusion: The results of the dynamic swallowing study indicated that the
      pharyngeal swallowing function of globus patients was not impaired.

PMID- 29204567
TI  - Objective and subjective scar aesthetics with topical Manuka honey post
      thyroidectomy: A randomized control study.
AB  - Objective: Leptospermum Honey (Manuka honey) has proven to be effective in
      improving acute and chronic wound healing presumably due to its antibacterial and
      anti-inflammatory properties. The aim is to determine if Manuka honey decreases
      scar formation and results in a cosmetically appealing scar. Methods: A
      prospective single-blinded randomized control trial was performed. All patients
      received an 8 cm incision. Patients randomized to honey treatment were instructed
      to apply Manuka honey paste topically to the incision site once per day post
      surgery for 4 weeks. The patients' scar was then analyzed objectively by a
      blinded observer and subjectively at 4 and 8 weeks postoperatively. The primary
      outcome measure used was the Patient and Observer Scar Assessment Scale (POSAS).
      Results: A total of 21 patients completed the entire scar analysis (honey
      treatment = 9, standard treatment = 12). There was no statistically significant
      difference between patient scar assessment scale and observer scar assessment
      scale at 4 and 8 weeks postoperatively. Conclusion: Despite Leptospermum Honey's
      reported anti-inflammatory and antibacterial properties, this study did not show
      a difference in scar appearance when applied.

PMID- 29204569
TI  - Assessment of rock musician's efferent system functioning using contralateral
      suppression of otoacoustic emissions.
AB  - Objective: Contralateral suppression of oto acoustic emission (OAE) is referred
      as activation of efferent system. Previous literature mentioned about the
      importance of contralateral suppression of OAEs as a tool to assess efferent
      system in different groups of population. There is dearth of literature to
      explore the efferent system function in experienced musicians exposed to rock
      music using TEOAEs and DPOAEs. Methods: Two groups of participant (14 rock
      musicians and 14 non-musicians) in the age range of 18-25 years were involved in
      the study. Contralateral suppression of TEOAEs and DPOAEs were measured using ILO
      (Version 6) in both groups. Results: Descriptive statistics showed higher
      suppression of TEOAEs and DPOAEs in rock-musicians at most of the frequencies in
      comparison to non-musicians. For DPOAE measures, Mann Whitney U test results
      revealed significantly greater DPOAE suppression only at 1 kHz and 3 kHz in rock
      musicians compared to non-musicians. For within group comparison, Kruskal Wallis
      test results revealed there were significant difference observed across most of
      the frequencies i.e. at 1 kHz, 3 kHz and 6 kHz. For TEOAE measures, Mann Whitney
      U test results revealed that only at 2 kHz, TEOAE suppression in rock-musician
      was significantly greater compared to non-musicians. Similarly, Kuskal Wallis
      test results revealed that within group there were no significant differences
      observed for most of the frequencies except 2 kHz. Conclusions: Based on the
      above finding, present study concludes that rock musicians are having better
      efferent system compared to non-musicians. No suppression effect at few
      frequencies probably indicates more vulnerability at those frequencies.
      Contralateral suppression of DPOAE shows more significant finding in comparison
      to contralateral suppression of TEOAEs in present study.

PMID- 29204568
TI  - Deep neck space infection - A retrospective study of 270 cases at tertiary care
      center.
AB  - Objective: To review the clinical findings in deep neck infections and
      identification predisposing factors of these complications. Methods: In this
      study, 270 patients with deep neck infections were studied retrospectively, study
      conducted in the Department of Ear, Nose and Throat, Dr. Shankarrao Chavan
      Government Medical College, Nanded, Maharashtra, India, from March 2013 to March
      2016. Results: Analysis showed that males are most likely to have deep neck space
      infections (DNSI). Odontogenic and tonsillar causes were the more frequent ones.
      Staphylococcus aureus and Streptococcus species were the microorganisms more
      commonly isolated. Conclusion: DNSI remains a common and challenging disease for
      otorhinolaryngologists, and should be treated on emergency basis. In developing
      countries, lack of adequate nutrition, poor oral hygiene, tobacco chewing,
      smoking and beetle nut chewing has led to an increased prevalence of dental and
      periodontal diseases. In present study, Odontogenic infections were the most
      common etiological factor for DNSI.

PMID- 29204570
TI  - Biofilms in chronic rhinosinusitis: Pathophysiology and therapeutic strategies.
AB  - Background: There is increasing evidence that biofilms are critical to the
      pathophysiology of chronic infections including chronic rhinosinusitis (CRS).
      Until relatively recently, our understanding of biofilms was limited. Recent
      advances in methods for biofilm identification and molecular biology have offered
      new insights into the role of biofilms in CRS. With these insights, investigators
      have begun to investigate novel therapeutic strategies that may disrupt or
      eradicate biofilms in CRS. Objective: This review seeks to explore the evidence
      implicating biofilms in CRS, discuss potential anti-biofilm therapeutic
      strategies, and suggest future directions for research. Results: The existing
      evidence strongly supports the role of biofilms in the pathogenesis of CRS.
      Several anti-biofilm therapies have been investigated for use in CRS and these
      are at variable stages of development. Generally, these strategies: 1) neutralize
      biofilm microbes; 2) disperse existing biofilms; or 3) disrupt quorum sensing.
      Several of the most promising anti-biofilm therapeutic strategies are reviewed.
      Conclusions: A better understanding of biofilm function and their contribution to
      the CRS disease process will be pivotal to the development of novel treatments
      that may augment and, potentially, redefine the CRS treatment paradigm. There is
      tremendous potential for future research.

PMID- 29204571
TI  - Hypoglossal nerve stimulation for obstructive sleep apnea: A review of the
      literature.
AB  - Objective: To review the indications and clinical evidence supporting hypoglossal
      nerve stimulation (HNS) therapy for the treatment of moderate-to-severe
      obstructive sleep apnea (OSA). Methods: Peer reviewed literature on hypoglossal
      nerve stimulation therapy for obstructive sleep apnea from 2001 to 2016. Results:
      The only currently FDA-approved HNS device for the treatment of moderate-to
      severe OSA is produced by Inspire Medical Systems, which recently published its
      36-month outcomes data from its Stimulation Therapy for Apnea Reduction (STAR)
      trial. HNS therapy is currently indicated for moderate-to-severe OSA patients who
      are CPAP-intolerant, have a body mass index <32, apnea-hypopnea index <50, and
      without a concentric pattern of upper airway collapse on sleep endoscopy.
      Conclusions: Data from the STAR trial suggests that a subset of OSA patients can
      achieve a significant therapeutic response from hypoglossal nerve stimulation.
      However, these results may be limited in their generalizability to the broader
      OSA population.

PMID- 29204572
TI  - Summary and consensus in 7th International Conference on acoustic neuroma: An
      update for the management of sporadic acoustic neuromas.
AB  - Sporadic vestibular schwannoma (acoustic neuroma) is a benign tumor arising from
      cochleovestibular nerve. Nowadays, various specialties and medical centers are
      treating this disease, and the multidisciplinary collaboration is the trend. In
      an effort to promote a uniform standard for reporting clinical results, even for
      treatment indications, the mainly controversies were posed and discussed during
      the 7th International Conference on acoustic neuroma, and the agreement was
      summarized by the Committee of this conference. The main symptoms grading and
      tumor stage should note its name of classification for making them comparable.
      The goal of the modern managements for vestibular schwannoma is to improve the
      quality of life with lower mortality, lower morbidity and better neurological
      function preservation. The experience of surgical team and their preference might
      be a major factor for the outcome. Because of lacking of long-term follow-up
      large data after radiotherapy, and with the development of microsurgery,
      radiotherapy is now less recommended except for recurrent cases or elderly
      patients.

PMID- 29204573
TI  - Protective and antifungal properties of Nanodisk-Amphotericin B over commercially
      available Amphotericin B.
AB  - Objective: Amphotericin B (AMB), a potent antifungal agent, has been employed as
      topical and systemic therapy for sinonasal fungal infections. A novel formulation
      of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of
      fungal infections has been recently developed to provide greater protection from
      AMB toxicity than current, clinically approved lipid-based formulations. The
      objective of the current study was to evaluate the safety and potency of ND-AMB
      for sinonasal delivery using an in vitro model. Methods: Human sinonasal tissue
      was harvested during endoscopic sinus surgery and grown at air-liquid interface
      until well-differentiated. Cultures were exposed to ND-AMB vs AMB and changes in
      K+ permeability and resistance were measured and recorded via Ussing chamber
      assay. Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic
      assay. Potency was assessed using real-time PCR measurement of the Aspergillus
      fumigatus 18S rRNA. Results: Ussing chamber studies revealed K+ currents that
      increased rapidly within 30 s of adding AMB (10 MUg/mL) to the apical side,
      indicating apical membranes had become permeable to K+ ions. In contrast,
      negligible induction of K+ current was obtained following addition of ND-AMB [AMB
      = (107.7 +/- 15.9) MUA/cm2 AMB vs ND-AMB = (2.3 +/- 0.7) MUA/cm2 ND-AMB; P =
      0.005]. ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P
      < 0.05). There was no difference in ciliary beat frequency between the two groups
      (P = 0.96). The expression of A. fumigatus 18S rRNA with exposure of lower dose
      of ND-AMB was significantly lower compared to that with AMB (P < 0.05).
      Conclusions: Data from the present study suggests ND-AMB protects human nasal
      epithelia membranes from AMB toxicity by protecting against apical cell K+
      permeability while maintaining uncompromised antifungal property compared to AMB.
      ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.

PMID- 29204574
TI  - Variables associated with olfactory disorders in adults: A U.S. population-based
      analysis.
AB  - Objective: Olfactory dysfunction is known to have significant social,
      psychological, and safety implications. Despite increasingly recognized
      prevalence, potential risk factors for olfactory loss have been arbitrarily
      documented and knowledge is limited in scale. The aim of this study is to
      identify potential demographic and exposure variables correlating with olfactory
      dysfunction. Methods: Cross-sectional analysis of the 2011-2012 and 2013-2014
      editions of the National Health Examination and Nutrition Survey was performed.
      The utilized survey reports from a nationally representative sample of about 5000
      persons each year located in counties across the United States. There is an
      interview and physical examination component which includes demographic,
      socioeconomic, dietary, and health-related questions as well as medical, dental,
      physiologic measurements, and laboratory tests. 3594 adult respondents from 2011
      to 2012 and 3708 respondents from 2013 to 2014 were identified from the above
      population-based database. The frequency of self-reported disorders as well as
      performance on odor identification testing was determined in relation to
      demographic factors, occupational or environmental exposures, and urinary levels
      of environmental and industrial compounds. Results: In both subjective and
      objective analysis, smell disorders were significantly more common with
      increasing age. While the non-Hispanic Black and non-Hispanic Asian populations
      were less likely to report subjective olfactory loss, they, along with Hispanics,
      performed more poorly on odor identification than Caucasians. Those with limited
      education had a decreased prevalence of hyposmia. Women outperformed men on smell
      testing. Those reporting exposure to vapors were more likely to experience
      olfactory dysfunction, and urinary levels of manganese, 2-Thioxothiazolidine-4
      carboxylic acid, and 2-Aminothiazoline-4-carboxylic acid were lower among
      respondents with subjective smell disturbance. In odor detection, elevated serum
      levels of lead and urinary levels of 2,4 dichlorophenol were associated with
      anosmia and hyposmia, respectively. Conclusions: This study provides current,
      population-based data identifying demographic and exposure elements related to
      smell disturbances in U.S. adults. Age, race, gender, education, exposure to
      vapors, urinary levels of manganese, 2-Thioxothiazolidine-4-carboxylic acid, 2
      Aminothiazoline-4-carboxylic acid, 2,4 dichlorophenol, and serum lead levels were
      all implicated in smell disturbance. Care should be taken in interpretation due
      to lack of consistency between subjective and objective measures of olfaction as
      well as limitations related to population-based data. Prospective trials are
      indicated to further elucidate these relationships.

PMID- 29204575
TI  - Healing of the nasal septal mucosa in an experimental rabbit model of mucosal
      injury.
AB  - Objective: The aim of this study was to investigate the regeneration process of
      the nasal mucosa after a surgically created mucosal defect in the rabbit nasal
      septum, and to evaluate the effects of different interventions. Methods: A 7 mm
      diameter circular mucosal defect was made in the septum of forty New Zealand
      white rabbits. The rabbits were divided into four groups (ten rabbits in each
      group) according to the type of intervention; no treatment (control), silastic
      sheet (SS), hyaluronic acid (HA), and silastic sheet and hyaluronic acid (SS +
      HA) group. The diameter of the defect, mucosal thickness, epithelial thickness,
      and ciliated cell count were evaluated every week for five weeks. Results: The
      average diameter of the defect in the control group were 5.1, 3.65, 1.2, 0.75,
      and 0.05 mm at postoperative 1, 2, 3, 4, and 5 weeks. In the SS group, the
      diameter decreased to 4.35, 2.1, 0.35, 0.15, and 0 mm at postoperative 1, 2, 3,
      4, and 5 weeks, respectively, in which the mean diameter of the postoperative
      week 2 was significantly smaller compared to control (3.65 mm vs. 2.1 mm, P =
      0.039). For the HA group and SS + HA group, the diameter of the defect did not
      show a significant difference from the control group during the five weeks. The
      mucosal thickness, epithelial thickness, and ciliated cell count of the
      regenerated mucosa were not significantly different among the groups. Conclusion:
      The regeneration process of the nasal septal mucosa was identified using a novel
      rabbit model. Mucosal regeneration can be accelerated by applying silastic
      sheets.

PMID- 29204576
TI  - Comparison of 3 mm versus 4 mm rigid endoscope in diagnostic nasal endoscopy.
AB  - Objective: Compare nasal endoscopy with 3 mm versus conventional 4 mm rigid 30
      degrees  endoscopes for visualization, patient comfort, and examiner ease.
      Methods: Ten adults with no previous sinus surgery underwent bilateral nasal
      endoscopy with both 4 mm and 3 mm endoscopes (resulting in 20 paired nasal
      endoscopies). Visualization, patient discomfort and examiner's difficulty were
      assessed with every endoscopy. Sino-nasal structures were checked on a list if
      visualized satisfactorily. Patients rated discomfort on a standardized numerical
      pain scale (0-10). Examiners rated difficulty of examination on a scale of 1-5 (1
      = easiest). Results: Visualization with 3 mm endoscope was superior for the
      sphenoid ostium (P = 0.002), superior turbinate (P = 0.007), spheno-ethmoid
      recess (P = 0.006), uncinate process (P = 0.002), cribriform area (P = 0.007),
      and Valve of Hasner (P = 0.002). Patient discomfort was not significantly
      different for 3 mm vs. 4 mm endoscopes but correlated with the examiners'
      assessment of difficulty (r = 0.73). The examiner rated endoscopy with 4 mm
      endoscopes more difficult (P = 0.027). Conclusions: The 3 mm endoscope was
      superior in visualizing the sphenoid ostium, superior turbinate, spheno-ethmoid
      recess, uncinate process, cribriform plate, and valve of Hasner. It therefore may
      be useful in assessment of spheno-ethmoid recess, nasolacrimal duct, and
      cribriform area pathologies. Overall, patients tolerated nasal endoscopy well.
      Though patient discomfort was not significantly different between the endoscopes,
      most discomfort with 3 mm endoscopes was noted while examining structures
      difficult to visualize with the 4 mm endoscope. Patients' discomfort correlated
      with the examiner's assessment of difficulty.

PMID- 29204577
TI  - Evidence for a 'preinvasive' variant of fungal sinusitis: Tissue invasion without
      angioinvasion.
AB  - Clinical experience has suggested the existence of an intermediate form of fungal
      sinusitis between the categories of non-invasive fungal sinusitis (non-IFS) and
      invasive fungal sinusitis (IFS). This fungal sinusitis variant demonstrates
      unhealthy mucosa by endoscopy with fungal invasion, but lacks angioinvasion
      microscopically, representing what clinically behaves as a 'pre-invasive' subtype
      of fungal sinusitis. Unlike non-IFS disease, patients with pre-invasive fungal
      sinusitis were still felt to require anti-fungal medications due to histologic
      presence of invasive fungus. While sharing some clinical features of IFS, these
      'intermediate' patients were successfully spared extended and repeated surgical
      debridements given the microscopic findings, and have been successfully treated
      with shorter courses of antifungal therapy. These select patients have had
      favorable outcomes when managed in a judicious and semi-aggressive manner, in an
      undefined zone between the treatments for routine fungal ball and aggressive IFS.

PMID- 29204578
TI  - Nasal septum suture combined with inferior turbinate coblation after septoplasty:
      Does it improve quality of life and reduce complications?
AB  - Objective: Nasal packing is routinely applied after septoplasty. Patients,
      however, report feeling very uncomfortable while the packing is in place. The aim
      of this study was to compare the effects of nasal septum suture combined with
      inferior turbinate coblation to the effects of nasal packing after septoplasty.
      Methods: In this study, 135 patients undergoing septoplasty were divided into 3
      groups: group 1 patients had microdebrider with packing, group 2 received
      coblation with packing and group 3 had coblation with suture. Early postoperative
      quality of life and complications were compared between the 3 groups. Results:
      The patients in group 1 experienced the most postoperative nasal pain, headache,
      dysphagia, sleep disturbance and bleeding on the night of surgery; while the
      patients in group 3 experienced the fewest symptoms. No difference in epiphora
      was observed between the 3 groups. More pain and bleeding were experienced when
      comparing the pack removal (Group 1 and 2) with the clearance of the nasal cavity
      (Group 3). We noted one case of postoperative bleeding in group 1, one septal
      hematoma in group 1 and a second septal hematoma in group 2. No such
      postoperative complications were found in group 3. Conclusion: Nasal septum
      suture combined with inferior turbinate coblation was not only associated with
      less pain, increased patient satisfaction and an improved quality of life; but
      also reduced postoperative complications. Our results confirm that it is a more
      comfortable, reliable alternative to the more common nasal packing.

PMID- 29204579
TI  - Ocular cranial nerve palsies secondary to sphenoid sinusitis.
AB  - Objective: The clinical presentation of sphenoid sinusitis can be highly
      variable. Rarely, sphenoid sinusitis may present with cranial nerve complications
      due to the proximity of these structures to the sphenoid sinus. Method: A case
      series from Rabin Medical Center and all cases of cranial nerves palsies
      secondary to sphenoid sinusitis that have been reported in the literature were
      reviewed. Results: Seventeen patients were identified. The abducent nerve was the
      most common cranial nerve affected (76%), followed by the oculomotor nerve (18%).
      One patient had combined oculomotor, trochlear and abducent palsies. The most
      common pathology was isolated purulent sphenoid sinusitis in 64% followed by
      allergic fungal sinusitis (AFS) in 18%, and fungal infection in 18%. 94% had an
      acute presentation. The majority (85%) received a combined intravenous
      antibiotics and surgical treatment. The remainder received conservative treatment
      alone. Complete recovery of cranial nerve palsy was noted in 82% during follow
      up. Conclusion: Sphenoid sinusitis presenting as diplopia and headaches is rare.
      A neoplastic process must be ruled out and early surgical intervention with
      intravenous antimicrobial therapy carry an excellent outcome with complete
      resolution of symptoms.

PMID- 29204580
TI  - Etiology of sinonasal inverted papilloma: A narrative review.
AB  - Objective: Sinonasal inverted papilloma (IP) is a benign and uncommon tumor of
      the nasal cavity and paranasal sinuses with a tendency for recurrence and even
      malignant transformation. Though the morphology and clinical behavior of this
      lesion has been well described, its etiology remains controversial. Methods:
      Computerized searches were performed in PubMed, Scopus, and Google scholar
      through May 2015. In this review, etiologic factors including human papilloma
      virus (HPV), Epstein-Barr virus (EBV), cell cycle related proteins and angiogenic
      factors, occupational and environmental exposures, and chronic inflammation, will
      be discussed. Results: Many studies indicate that HPV has been detected in a
      significant percentage of IP, while EBV has not been shown to be significantly
      associated. Certain cell cycle regulatory factors and angiogenic proteins
      contribute to the dysregulation of proliferation and apoptosis, and facilitate
      migration and tumor invasion. Occupational exposures, such as welding and organic
      solvents, have been implicated, and smoking seems more critical to recurrence and
      dysplasia rather than initial IP occurrence. Chronic inflammation may also have a
      causative relationship with inverted papilloma, but the mechanism is unclear.
      Conclusions: Though etiology of sinonasal IP remains controversial, the studies
      reviewed here indicate a role for viral infection, cell cycle and angiogenic
      factors, environmental and occupational exposure, and chronic inflammation.
      Further study on etiologic factors is necessary for clinical guidance and
      therapeutic targets.

PMID- 29204581
TI  - Allergic fungal sinusitis caused by Schizophyllum commune.
AB  - A case of allergic fungal sinusitis (AFS) due to Schizophyllum commune was
      reported. The pathogen was identified using molecular bioanalysis. The patient
      underwent the functional endoscopic sinus surgery followed by the radical
      maxillary sinusotomy with canine fossa trephine. This case suggested that
      complete surgery allowed optimal disease clearance for AFS caused by
      Schizophyllum commune.

PMID- 29204582
TI  - Publication trends in obstructive sleep apnea: Evidence of need for more
      evidence.
AB  - Objective: Published research in obstructive sleep apnea (OSA) appears limited
      despite OSA being a highly prevalent adult and pediatric disease leading to many
      adverse outcomes if left untreated. We aimed to quantify the deficit in OSA
      scientific literature in order to provide a novel way of identifying gaps in
      knowledge and a need for further research inquiry. Methods: This was a
      Bibliometric analysis study. Using Ovid Medline database we analyzed and compared
      research output (medical and surgical) between adult OSA and similarly prevalent
      chronic conditions (Type II diabetes (T2DM), coronary artery disease (CAD) and
      osteoarthritis (OA)) from December 2016 up to fifty years prior. Linear graphs
      were utilized to trend collected data. Utilizing same strategy, we compared
      publication trends for pediatric OSA to asthma and gastroesophageal reflux (GER).
      Results: Adult OSA publications (n = 9314) were significantly underrepresented
      when compared to T2DM (n = 66,023), CAD (n = 31,526) and OA (n = 34,123). Linear
      plots demonstrated that despite increasing number of publications this disparity
      persisted annually. Surgical literature composed 10.4% (n = 972) of adult OSA
      publications and reached a plateau in the last ten years. Pediatric OSA (n =
      2994) had less research output when compared to asthma (n = 47,442) and GER (n =
      6705). However, over past five years pediatric OSA surpassed GER in annual number
      of publications. Surgical literature represented 23.1% (n = 693) of pediatric OSA
      publications and continued increasing over past ten years. Study methodologies
      for both adult and pediatric OSA showed a lack of randomized controlled trials
      and meta-analyses in comparison to other diseases. Conclusion: Our review shows
      substantial deficit in total, annual and surgical adult OSA published research
      compared to similarly prevalent diseases. This trend is not entirely observed in
      pediatric OSA literature.

PMID- 29204583
TI  - OSA treatment history in an upper airway stimulation trial cohort.
AB  - Objectives: Analyze the obstructive sleep apnea (OSA) treatment history in a
      group of participants who enrolled in a hypoglossal nerve stimulation trial.
      Methods: Moderate-severe OSA patients with difficulty adhering to CPAP presented
      for enrollment in a multicenter trial. Self-reported history on prior OSA medical
      therapy was collected at enrollment, including OSA diagnosis date, CPAP start and
      stop dates, oral appliance trial, and reasons for discontinuation or non
      adherence. Results: The cohort consisted of 929 participants, 83% male, with a
      mean age (53.9 +/- 10.5) years. Ninety percent (n = 835) had complete CPAP
      information including 47% (n = 435) who discontinued therapy prior to enrollment
      and 43% (n = 400) who were still attempting CPAP but had inadequate adherence.
      Abandonment rates were 60% at 1-year, 73% at 3-years, and 86% at 5-years. Oral
      appliance therapy was attempted by 171 patients for mean (1.8 +/- 2.3) years,
      with 81% abandonment at 1 year, 89% at 3-years, and 94% at 5-years. Conclusions:
      In this CPAP-refractory cohort, high rates of CPAP abandonment were reported in
      the first several years with approximately half of the participants not receiving
      any treatment despite being diagnosed for >5 years. Close clinical follow-up and
      consideration of alternative treatment options is indicated in all OSA patients
      in order to ensure adequate longitudinal care.

PMID- 29204584
TI  - Anatomic measures of upper airway structures in obstructive sleep apnea.
AB  - Objective: Determine if anatomic dimensions of airway structures are associated
      with airway obstruction in obstructive sleep apnea (OSA) patients. Methods:
      Twenty-eight subjects with (n = 14) and without (n = 14) OSA as determined by
      clinical symptoms and sleep studies; volunteer sample. Skeletal and soft tissue
      dimensions were measured from radiocephalometry and magnetic resonance imaging.
      The soft palate thickness, mandibular plane-hyoid (MP-H) distance, posterior
      airway space (PAS) diameters and area, and tongue volume were calculated.
      Results: Compared to controls, the OSA group demonstrated a significantly longer
      MP-H distance (P = 0.009) and shorter nasal PAS diameter (P = 0.02). The PAS area
      was smaller (P = 0.002) and tongue volume larger in the OSA group (P = 0.004).
      The MP-H distance, PAS measurements, and tongue volume are of clinical relevance
      in OSA patients. Conclusions: A long MP-H distance, and small PAS diameters and
      area are significant anatomic measures in OSA; however the most substantial
      parameter found was a large tongue volume.

PMID- 29204585
TI  - Application of drug-induced sleep endoscopy in patients treated with upper airway
      stimulation therapy.
AB  - Objective: To determine the level of agreement among experienced operators of
      candidacy for upper airway stimulation (UAS) based on evaluation of drug-induced
      sleep endoscopy (DISE). Methods: The trial was designed as a single-blinded cross
      sectional study. Four otolaryngologists with extensive DISE experience were given
      63 video clips from the STAR trial video library. These videos were graded using
      the VOTE classification. Percentage agreement and Cohen's kappa (for inter-rater
      reliability) were calculated between pairs of reviewers, assessing palatal
      complete concentric collapse (CCC) and determining UAS eligibility. Subjects were
      also grouped based on collapse severity for each reviewer. Results: The reviewers
      had excellent (approximately 90%) agreement on findings at the level of the soft
      palate and tongue base. The inter-rater reliability for palatal CCC ranged from
      moderate to substantial. The agreement on determining the criteria for UAS
      implantation ranged from poor to moderate. All 4 upper airway structures as
      classified by the criteria of the VOTE were graded by all the reviewers as
      contributing to obstruction in a majority of subjects who were performed via
      application of DISE. Conclusion: Application of DISE remains a subjective
      examination, even among those experienced operators, therefore more studies need
      to be performed for evaluation of improvement in inter-rater reliability after
      implantation of training videos.

PMID- 29204586
TI  - Transoral robotic surgery for obstructive sleep apnea syndrome: Principles and
      technique.
AB  - Objective: The present study is a review of transoral robotic surgery (TORS) for
      the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods: The
      review presents the experience of the robotic center that developed the technique
      with regards to patient selection, surgical method, and post-operative care. In
      addition, the review provides results of a systematic review and meta-analysis of
      the complications and clinical outcomes of TORS when applied in the management of
      OSAHS. Results: The rate of success, defined as 50% reduction of pre-operative
      AHI and an overall AHI <20 events/h, is achieved in up to 76.6% of patients with
      a range between 53.8% and 83.3%. The safety of this approach is reasonable as the
      main complication (bleeding) affected 4.2% of patients (range 4.2%-5.3%).
      However, transient dysphagia (7.2%; range 5%-14%) does compromise the quality of
      life and must be discussed with patients preoperatively. Conclusions: TORS for
      the treatment of OSAHS appears to be a promising and safe procedure for patients
      seeking an alternative to traditional therapy. Appropriate patient selection
      remains an important consideration for successful implementation of this novel
      surgical approach requiring further research.

PMID- 29204587
TI  - Transoral robotic surgery vs. endoscopic partial midline glossectomy for
      obstructive sleep apnea.
AB  - Objective: To compare sleep-related outcomes in obstructive sleep apnea hypopnea
      syndrome (OSAHS) patients following base of tongue resection via robotic surgery
      and endoscopic midline glossectomy. Methods: This was a retrospective study. A
      total of 114 robotic and 37 endoscopic midline glossectomy surgeries were
      performed between July 2010 and April 2015 as part of single or multilevel
      surgery. Patients were excluded for indications other than sleep apnea or if
      complete sleep studies were not obtained. Thus, 45 robotic and 16 endoscopic
      surgeries were included in the analysis. Results: In the robotic surgery group
      there were statistically significant improvements in AHI [(44.4 +/- 22.6)
      events/h-(14.0 +/- 3.0) events/h, P < 0.001] Epworth Sleepiness Scale (12.3 +/-
      4.6 to 4.5 +/- 2.9, P < 0.001), and O2 nadir (82.0% +/- 6.1% to 85.0% +/- 5.4%, P
      < 0.001). In the endoscopic group there were also improvements in AHI (48.7 +/-
      30.2 to 27.4 +/- 31.9, P = 0.06), Epworth Sleepiness Scale (12.6 +/- 5.5 to 8.3
      +/- 4.5, P = 0.08), and O2 nadir (80.2% +/- 8.6% to 82.7% +/- 6.5%, P = 0.4).
      Surgical success rate was 75.6% and 56.3% in the robotic and endoscopic groups,
      respectively. Greater volume of tissue removed was predictive of surgical success
      in the robotic cases (10.3 vs. 8.6 ml, P = 0.02). Conclusions: Both robotic
      surgery and endoscopic techniques for tongue base reduction improve objective
      measures of sleep apnea. Greater success rates may be achieved with robotic
      surgery compared to traditional methods.

PMID- 29204588
TI  - Radiofrequency ablation of the lateral palatal space for snoring.
AB  - Objective: Pilot study to examine the effect of radiofrequency ablation (RFA) of
      the lateral palatal fat pad in patients with socially-disruptive snoring. Method:
      Snoring outcomes and complications were compared between a group of patients with
      treated with RFA ablation of the lateral soft palate fat pad with or without
      inferior turbinate reduction (8 patients) and another group undergoing inferior
      turbinate reduction alone (12 patients). Results: Snoring loudness and
      bothersomeness improved in the palate but not inferior turbinate group. Pain was
      mild and no major complications were observed. Conclusion: The study supports RFA
      ablation of the lateral palatal space as a potential low morbidity procedure for
      snoring.

PMID- 29204589
TI  - Hyoid myotomy and suspension without simultaneous palate or tongue base surgery
      for obstructive sleep apnea.
AB  - Objective: Determine the effects of hyoid myotomy and suspension (HMS) without
      concurrent palatal or tongue base sleep surgery for obstructive sleep apnea
      (OSA). Method: Patients with OSA treated with HMS were identified using CPT code
      (21685) at an academic and private sleep surgery clinic. Those who underwent
      concurrent palatal or tongue base sleep surgery were excluded. Outcomes included
      simultaneous procedures, apnea-hypopnea index (AHI), lowest oxyhemoglobin
      saturation (LSAT), and Epworth Sleepiness Scale (ESS). Results: Nineteen patients
      with OSA underwent HMS without palatal or tongue base sleep surgery. The average
      age at surgery was (55.3 +/- 13.5) years with a majority of patients being male
      (71%). Concurrent procedures included the following: torus mandibularis excision
      (n = 1), endoscopic sinus surgery (n = 4), septoplasty (n = 10), inferior
      turbinate reduction (n = 12), and nasal valve repair (n = 2). AHI improved
      significantly from (39.7 +/- 21.2) events/h to (22.6 +/- 22.7) events/h after HMS
      (P < 0.01), which represented a 43% reduction. LSAT significantly increased from
      (82.2% +/- 9.9%) to (86.6% +/- 6.2%), P < 0.01. There was no improvement in ESS
      after surgery (8.2 +/- 4.4) to (8.3 +/- 5.2), P = 0.904. A subset of patients
      with severe OSA (AHI > 30 events/h) had an improvement in AHI from (49.9 +/-
      16.6) events/h to (29.1 +/- 24.9) events/h, P < 0.01. Conclusion: HMS without
      palatal or tongue base sleep surgery improves OSA severity. It can be considered
      as a valid option in the treatment of OSA in appropriately-selected patients.

PMID- 29204591
TI  - Evaluating the Privacy Implications of Frequent Itemset Disclosure.
AB  - Frequent itemset mining is a fundamental data analytics task. In many cases, due
      to privacy concerns, only the frequent itemsets are released instead of the
      underlying data. However, it is not clear how to evaluate the privacy
      implications of the disclosure of the frequent item-sets. Towards this, in this
      paper, we define the k-distant-IFM-solutions problem, which aims to find k
      transaction datasets whose pair distance is maximized. The degree of difference
      between the reconstructed datasets provides a way to evaluate the privacy risk.
      Since the problem is NP-hard, we propose a 2-approximate solution as well as
      faster heuristics, and evaluate them on real data.

PMID- 29204590
TI  - Thirty years of endoscopic sinus surgery: What have we learned?
AB  - Prior to adaptation of endoscopic approaches for sinonasal pathology, patients
      regularly endured significant morbidity from open approaches to the sinonasal
      cavity that were often fraught with failure. With improvements in transnasal
      endoscopy, functional endoscopic sinus surgery subsequently emerged from the work
      of Messerklinger and other pioneers in the field. The popularity of endoscopic
      sinus surgery quickly escalated and expanded to pathology other than
      inflammation. Here, we discuss the evolution of endoscopic sinus surgery as it
      relates to improvements in understanding disease pathogenesis, improvements in
      instrumentation and expansion of indications.

PMID- 29204592
TI  - Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue
      Syndrome (CFS) By Course of Illness.
AB  - Past research has subtyped patients with Myalgic Encephalomyelitis (ME) and
      Chronic Fatigue Syndrome (CFS) according to factors related to illness onset,
      illness duration, and age. However, no classification system fully accounts for
      the wide range of symptom severity, functional disability, progression, and
      prognosis seen among patients. This study examined whether illness trajectories
      among individuals with CFS were predictive of different levels of symptomology,
      functional disability, and energy expenditure. Of the participants (N=541), the
      majority described their illness as Fluctuating (59.7%), with 15.9% Constantly
      Getting Worse, 14.1% Persisting, 8.5% Relapsing and Remitting, and 1.9%
      Constantly Getting Better. The illness courses were associated with significant
      differences in symptomology on select domains of the DSQ, functioning on select
      subscales of the SF-36, and on overall levels of energy expenditure. The
      significant symptomatic and functional differences between groups suggest that
      subtyping patients with CFS according to illness course is a promising method for
      creating more homogeneous groups of patients.

PMID- 29204593
TI  - Quantifying the thickness of the electrical double layer neutralizing a planar
      electrode: the capacitive compactness.
AB  - The spatial extension of the ionic cloud neutralizing a charged colloid or an
      electrode is usually characterized by the Debye length associated with the
      supporting charged fluid in the bulk. This spatial length arises naturally in the
      linear Poisson-Boltzmann theory of point charges, which is the cornerstone of the
      widely used Derjaguin-Landau-Verwey-Overbeek formalism describing the colloidal
      stability of electrified macroparticles. By definition, the Debye length is
      independent of important physical features of charged solutions such as the
      colloidal charge, electrostatic ion correlations, ionic excluded volume effects,
      or specific short-range interactions, just to mention a few. In order to include
      consistently these features to describe more accurately the thickness of the
      electrical double layer of an inhomogeneous charged fluid in planar geometry, we
      propose here the use of the capacitive compactness concept as a generalization of
      the compactness of the spherical electrical double layer around a small macroion
      (Gonzalez-Tovar et al., J. Chem. Phys. 2004, 120, 9782). To exemplify the
      usefulness of the capacitive compactness to characterize strongly coupled charged
      fluids in external electric fields, we use integral equations theory and Monte
      Carlo simulations to analyze the electrical properties of a model molten salt
      near a planar electrode. In particular, we study the electrode's charge
      neutralization, and the maximum inversion of the net charge per unit area of the
      electrode-molten salt system as a function of the ionic concentration, and the
      electrode's charge. The behaviour of the associated capacitive compactness is
      interpreted in terms of the charge neutralization capacity of the highly
      correlated charged fluid, which evidences a shrinking/expansion of the electrical
      double layer at a microscopic level. The capacitive compactness and its first two
      derivatives are expressed in terms of experimentally measurable macroscopic
      properties such as the differential and integral capacity, the electrode's
      surface charge density, and the mean electrostatic potential at the electrode's
      surface.

PMID- 29204594
TI  - Exploring the solid state phase transition in dl-norvaline with terahertz
      spectroscopy.
AB  - dl-Norvaline is a molecular crystal at room temperature and it undergoes a phase
      transition when cooled below 190 K. This phase transition is believed to be
      Martensitic, thus making it of particular interest for molecular machines. In
      this paper we investigate this phase transition by measuring its terahertz (THz)
      spectrum over a range of temperatures. Temperature-dependent THz time-domain
      spectroscopy (THz-TDS) measurements reveal that the transition temperature (Tbeta
      >alpha) is 190 K. The influence of nucleation seeds was analyzed by determining
      the Tbeta->alpha of molecular crystals with varying grain size. Grains of 5 MUm
      or less result in a lower transition temperature (Tbeta->alpha = 180 K) compared
      to larger grains of 125-250 MUm (Tbeta->alpha = 190 K). Additionally, we gain
      insight into the physical process of the phase transition via temperature
      dependent THz-TDS spectra of doped and mixed molecular crystals. The addition of
      molecular dopants, which differ from dl-norvaline only at the end of the side
      chain which resides in the hydrophobic layers of the crystal, decreases Tbeta
      >alpha. This is consistent with a solid-solid phase transition in which the unit
      cell shifts along this hydrophobic layer, and it leads us to believe that the
      phase transition in dl-norvaline is Martensitic in nature.

PMID- 29204595
TI  - Where's water? The many binding sites of hydantoin.
AB  - Prebiotic hydantoin and its complexes with one and two water molecules are
      investigated using high-resolution broadband rotational spectroscopy in the 2-8
      GHz frequency range. The hyperfine structure due to the nuclear quadrupole
      coupling of the two 14N atoms is analysed for the monomer and the complexes. This
      characteristic hyperfine structure will support a definitive assignment from low
      frequency radioastronomy data. Experiments with H218O provide accurate
      experimental information on the preferred binding sites of water, which are
      compared with quantum-chemically calculated coordinates. In the 2-water
      complexes, the water molecules bind to hydantoin as a dimer instead of
      individually, indicating the strong water-water interactions. This information
      provides first insight on how hydantoin interacts with water on the molecular
      level.

PMID- 29204596
TI  - Overlapping Surgery-Perspectives From the Other Side of the Table.

PMID- 29204597
TI  - Association of Overlapping Surgery With Increased Risk for Complications
      Following Hip Surgery: A Population-Based, Matched Cohort Study.
AB  - Importance: Overlapping surgery, also known as double-booking, refers to a
      controversial practice in which a single attending surgeon supervises 2 or more
      operations, in different operating rooms, at the same time. Objective: To
      determine if overlapping surgery is associated with greater risk for
      complications following surgical treatment for hip fracture and arthritis.
      Design, Setting, and Participants: This was a retrospective population-based
      cohort study in Ontario, Canada (population, 13.6 million), for the years 2009 to
      2014. There was 1 year of follow-up. This study encompassed 2 large cohorts. The
      "hip fracture" cohort captured all persons older than 60 years who underwent
      surgery for a hip fracture during the study period. The "total hip arthroplasty"
      (THA) cohort captured all primary elective THA recipients for arthritis during
      the study period. We matched overlapping and nonoverlapping hip fractures by
      patient age, patient sex, surgical procedure (for the hip fracture cohort),
      primary surgeon, and hospital. Exposures: Procedures were identified as
      overlapping if they overlapped with another surgical procedure performed by the
      same primary attending surgeon by more than 30 minutes. Main Outcomes and
      Measures: Complication (infection, revision, dislocation) within 1 year. Results:
      There were 38 008 hip fractures, and of those, 960 (2.5%) were overlapping (mean
      age of patients, 66 years [interquartile range, 57-74 years]; 503 [52.4%] were
      female). There were 52 869 THAs and of those, 1560 (3.0%) overlapping (mean age,
      84 years [interquartile range, 77-89 years]; 1293 [82.9%] were female). After
      matching, overlapping hip fracture procedures had a greater risk for a
      complication (hazard ratio [HR], 1.85; 95% CI, 1.27-2.71; P = .001), as did
      overlapping THA procedures (HR, 1.79; 95% CI, 1.02-3.14; P = .04). Among
      overlapping hip fracture operations, increasing duration of operative overlap was
      associated with increasing risk for complications (adjusted odds ratio, 1.07 per
      10-minute increase in overlap; P = .009). Conclusions and Relevance: Overlapping
      surgery was relatively rare but was associated with an increased risk for
      surgical complications. Furthermore, increasing duration of operative overlap was
      associated with an increasing risk for complications. These findings support the
      notion that overlapping provision of surgery should be part of the informed
      consent process.

PMID- 29204598
TI  - Finding Health Care Prices Online-How Difficult Is It to Be an Informed Health
      Care Consumer?

PMID- 29204599
TI  - A Rapid Irregular Rhythm in a Healthy, Young Patient: How Fast Can You Go?

PMID- 29204600
TI  - Further Actions Are Needed to Prevent Maternal Deaths From Epilepsy.

PMID- 29204601
TI  - Receptive Vocabulary, Cognitive Flexibility, and Inhibitory Control
      Differentially Predict Older and Younger Adults' Success Perceiving Speech by
      Talkers With Dysarthria.
AB  - Purpose: Previous research has demonstrated equivocal findings related to the
      effect of listener age on intelligibility ratings of dysarthric speech. The aim
      of the present study was to investigate the mechanisms that support younger and
      older adults' perception of speech by talkers with dysarthria. Method: Younger
      and older adults identified words in phrases produced by talkers with dysarthria.
      Listeners also completed assessments on peripheral hearing, receptive vocabulary,
      and executive control functions. Results: Older and younger adults did not differ
      in their ability to perceive speech by talkers with dysarthria. Younger adults'
      success in identifying words produced by talkers with dysarthria was associated
      only with their hearing acuity. In contrast, older adults showed effects of
      working memory and cognitive flexibility and interactions between hearing acuity
      and receptive vocabulary and between hearing acuity and inhibitory control.
      Conclusions: Although older and younger adults had equivalent performance
      identifying words produced by talkers with dysarthria, older adults appear to
      utilize more cognitive support to identify those words.

PMID- 29204602
TI  - Encouraging New Uses for Old Drugs.

PMID- 29204603
TI  - Trends in U.S. Drug Overdose Deaths in Non-Hispanic Black, Hispanic, and Non
      Hispanic White Persons, 2000-2015.

PMID- 29204604
TI  - Hair Loss in a Young Child.

PMID- 29204605
TI  - Association Between Microinfarcts and Blood Pressure Trajectories.
AB  - Importance: Cerebral microinfarcts are associated with increased risk of
      cognitive impairment and may have different risk factors than macroinfarcts.
      Subcortical microinfarcts are associated with declining blood pressure (BP) in
      elderly individuals. Objective: To investigate BP slopes as a risk factor for
      microinfarcts. Design, Setting, and Participants: From the population-based Mayo
      Clinic Study of Aging, 303 of 1158 individuals (26.2%) in this cohort study
      agreed to have an autopsy between November 1, 2004, and March 31, 2016. Cerebral
      microinfarcts were identified and classified as cortical or subcortical. Baseline
      and BP trajectories were compared for groups with no microinfarcts, subcortical
      microinfarcts, and cortical microinfarcts. A secondary logistic regression
      analysis was performed to assess associations of subcortical microinfarcts with
      midlife hypertension, as well as systolic and diastolic BP slopes. Main Outcomes
      and Measures: The presence of cerebral microinfarcts using BP slopes. Results: Of
      the 303 participants who underwent autopsy, 297 had antemortem BP measurements.
      Of these, 177 (59.6%) were men; mean (SD) age at death was 87.2 (5.3) years. The
      autopsied individuals and the group who died but were not autopsied were similar
      for all demographics except educational level with autopsied participants having
      a mean of 1 more year of education (1.06; 95% CI, 0.66-1.47 years; P < .01).
      Among 297 autopsied individuals with antemortem BP measurements, 47 (15.8%) had
      chronic microinfarcts; 30 (63.8%) of these participants were men. Thirty (63.8%)
      had cortical microinfarcts, 19 (40.4%) had subcortical microinfarcts, and 4
      (8.5%) had only infratentorial microinfarcts. Participants with microinfarcts did
      not differ significantly on baseline systolic (mean difference, -1.48; 95% CI, 
      7.30 to 4.34; P = .62) and diastolic (mean difference of slope, -0.90; 95% CI, 
      3.93 to 2.13; P = .56) BP compared with those with no microinfarcts. However,
      participants with subcortical microinfarcts had a greater annual decline
      (negative slope) of systolic (mean difference of slope, 4.66; 95% CI, 0.13 to
      9.19; P = .04) and diastolic (mean difference, 3.33; 95% CI, 0.61 to 6.06; P =
      .02) BP. Conclusions and Relevance: Subcortical microinfarcts were associated
      with declining BP. Future studies should investigate whether declining BP leads
      to subcortical microinfarcts or whether subcortical microinfarcts are a factor
      leading to declining BP.

PMID- 29204606
TI  - Modeling Speech Level as a Function of Background Noise Level and Talker-to
      Listener Distance for Talkers Wearing Hearing Protection Devices.
AB  - Purpose: Studying the variations in speech levels with changing background noise
      level and talker-to-listener distance for talkers wearing hearing protection
      devices (HPDs) can aid in understanding communication in background noise.
      Method: Speech was recorded using an intra-aural HPD from 12 different talkers at
      5 different distances in 3 different noise conditions and 2 quiet conditions.
      Results: This article proposes models that can predict the difference in speech
      level as a function of background noise level and talker-to-listener distance for
      occluded talkers. The proposed model complements the existing model presented by
      Pelegrin-Garcia, Smits, Brunskog, and Jeong (2011) and expands on it by taking
      into account the effects of occlusion and background noise level on changes in
      speech sound level. Conclusions: Three models of the relationship between vocal
      effort, background noise level, and talker-to-listener distance for talkers
      wearing HPDs are presented. The model with the best prediction intervals is a
      talker-dependent model that requires the users' unoccluded speech level at 10 m
      as a reference. A model describing the relationship between speech level, talker
      to-listener distance, and background noise level for occluded talkers could
      eventually be incorporated with radio protocols to transmit verbal communication
      only to an intended set of listeners within a given spatial range-this range
      being dependent on the changes in speech level and background noise level.

PMID- 29204607
TI  - Longitudinal Associations Across Prematurity, Attention, and Language in School
      Age Children.
AB  - Purpose: This research note explores the potential role of attention in mediating
      previously reported associations between language outcomes and prematurity.
      Method: As a follow-up investigation to Mahurin Smith, DeThorne, Logan, Channell,
      and Petrill (2014), we employed multilevel modeling to analyze longitudinal data
      on language and attention collected when children were, on average, ages of 7, 8,
      and 10 years. The sample of 114 children taken from the Western Reserve Reading
      and Math Project was selected to oversample children with a history of
      prematurity while also controlling for differences in confounding influences such
      as age, gender, parental education, and race. Results: As predicted, attention
      differentially predicted language outcomes based on form of measurement.
      Specifically, parent and examiner ratings of attention were significantly
      associated with standardized test performance at all 3 time points (R2 = 15.2%
      20%). Associations between attention and language sample measures were less
      consistent across home visits and tended to be smaller in effect size.
      Conclusion: Attention abilities are associated with children's language
      performance even in the absence of an attention-deficit/hyperactivity disorder
      diagnosis. Clinical implications, particularly as related to assessment, are
      discussed.

PMID- 29204609
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204608
TI  - Magnitude of Neck-Surface Vibration as an Estimate of Subglottal Pressure During
      Modulations of Vocal Effort and Intensity in Healthy Speakers.
AB  - Purpose: This study examined the relationship between the magnitude of neck
      surface vibration (NSVMag; transduced with an accelerometer) and intraoral
      estimates of subglottal pressure (P'sg) during variations in vocal effort at 3
      intensity levels. Method: Twelve vocally healthy adults produced strings of
      /palpha/ syllables in 3 vocal intensity conditions, while increasing vocal effort
      during each condition. Measures were made of P'sg (estimated during stop
      consonant closure), NSVMag (measured during the following vowel), sound pressure
      level, and respiratory kinematics. Mixed linear regression was used to analyze
      the relationship between NSVMag and P'sg with respect to total lung volume
      excursion, levels of lung volume initiation and termination, airflow, laryngeal
      resistance, and vocal efficiency across intensity conditions. Results: NSVMag was
      significantly related to P'sg (p < .001), and there was a significant, although
      small, interaction between NSVMag and intensity condition. Total lung excursion
      was the only additional variable contributing to predicting the NSVMag-P'sg
      relationship. Conclusions: NSVMag closely reflects P'sg during variations of
      vocal effort; however, the relationship changes across different intensities in
      some individuals. Future research should explore additional NSV-based measures
      (e.g., glottal airflow features) to improve estimation accuracy during voice
      production.

PMID- 29204610
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204611
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204612
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204613
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204614
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204615
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204616
TI  - Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain.

PMID- 29204617
TI  - Comparative Effectiveness of Routine Invasive Coronary Angiography for Managing
      Unstable Angina.

PMID- 29204618
TI  - Comparative Effectiveness of Routine Invasive Coronary Angiography for Managing
      Unstable Angina.

PMID- 29204619
TI  - Denial.

PMID- 29204620
TI  - Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel
      Deaconess Medical Center.
AB  - Aspirin exerts antiplatelet effects through irreversible inhibition of
      cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of
      cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task
      Force endorsed aspirin for primary prevention of cardiovascular disease. However,
      aspirin's role in cancer prevention is still emerging, and no groups currently
      recommend its use for this purpose. To help physicians balance the benefits and
      harms of aspirin in primary disease prevention, the Task Force issued a guideline
      titled, "Aspirin Use for the Primary Prevention of Cardiovascular Disease and
      Colorectal Cancer" in 2016. In the evidence review conducted for the guideline,
      cardiovascular disease mortality and colorectal cancer mortality were
      significantly reduced among persons taking aspirin. However, there was no
      difference in nonfatal stroke, cardiovascular disease mortality, or all-cause
      mortality, nor in total cancer mortality, among those taking aspirin. Aspirin
      users were found to be at increased risk for major gastrointestinal bleeding. In
      this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how
      they would apply it to a 57-year-old man considering starting aspirin for primary
      prevention. Our experts review the data on which the guideline is based, discuss
      how they would balance the benefits and harms of aspirin therapy, and explain how
      they would incorporate shared decision making into clinical practice.

PMID- 29204621
TI  - Terminal.

PMID- 29204623
TI  - Web Exclusives. Annals Graphic Medicine - Dear Doctor II.

PMID- 29204622
TI  - Dyslipidemia.
AB  - Dyslipidemia is an important risk factor for coronary artery disease and stroke.
      Long-term, prospective epidemiologic studies have consistently shown that persons
      with healthier lifestyles and fewer risk factors for coronary heart disease, and
      particularly those with favorable lipid profiles, have reduced incidence of
      coronary heart disease. Prevention and sensible management of dyslipidemia can
      markedly alter cardiovascular morbidity and mortality.

PMID- 29204627
TI  - The ACC/AHA 2017 Hypertension Guidelines: Both Too Much and Not Enough of a Good
      Thing?

PMID- 29204629
TI  - Search Images and Extrapolation Risk.

PMID- 29204630
TI  - Specialty Societies and Breast Cancer Screening Recommendations.

PMID- 29204631
TI  - Drug Trials Snapshots and Sexless Drug Labels.

PMID- 29204632
TI  - Considerations Concerning Disease Redefinition.

PMID- 29204633
TI  - Concerns About Conclusions of Self-monitoring of Blood Glucose.

PMID- 29204634
TI  - Search Images and Extrapolation Risk.

PMID- 29204635
TI  - Selection Does Not Equate Consumption.

PMID- 29204636
TI  - Search Images and Extrapolation Risk-Reply.

PMID- 29204637
TI  - Specialty Societies and Breast Cancer Screening Recommendations-Reply.

PMID- 29204638
TI  - Search Images and Extrapolation Risk-Reply.

PMID- 29204639
TI  - Drug Trials Snapshots and Sexless Drug Labels-Reply.

PMID- 29204640
TI  - Concerns About Conclusions of Self-monitoring of Blood Glucose-Reply.

PMID- 29204641
TI  - Considerations Concerning Disease Redefinition-Reply.

PMID- 29204642
TI  - Selection Does Not Equate Consumption-Reply.

PMID- 29204644
TI  - Topical Application of Mizoribine Suppresses CD4+ T-cell-Mediated Pathogenesis in
      Murine Dry Eye.
AB  - Purpose: We investigate the effect of topical application of mizoribine (MZR) eye
      drops on CD4+ T-cell-mediated immunity and epithelial damage in ocular surface of
      dry eye disease (DED). Methods: Topical application of MZR or vehicle eye drops
      was performed in mice subjected to desiccating stress (DS). The phenol red cotton
      test was used to measure tear production, and Oregon-green-dextran (OGD) staining
      was performed to assess corneal epithelial barrier function. PAS staining was
      used to quantify conjunctival goblet cells. Immunofluorescent staining and
      quantitative (q) RT-PCR were used to assess the expression of matrix
      metalloproteinase (MMP)-9 in corneal epithelium. qRT-PCR and ELISA were used to
      assess the production of TNF-alpha and IL-1beta in conjunctiva. Apoptosis in
      ocular surface was assessed by TUNEL and activation of caspase-8. CD4+ T-cell
      mediated immunity was evaluated by CD4 immunohistochemistry and production of T
      helper cytokines, including IFN-gamma, IL-13, and IL-17A in conjunctiva. Results:
      Compared to vehicle control mice, topical MZR-treated mice showed increased tear
      production, decreased goblet cell loss, and improved corneal barrier function.
      Topical application of MZR suppressed the expression of MMP-9 in corneal
      epithelium and apoptosis in ocular surface, while it had no obvious effect on
      production of TNF-alpha and IL-1beta in conjunctiva. Topical application of MZR
      decreased CD4+ T cells infiltration, with decreased production of IFN-gamma and
      IL-17A, and increased production of IL-13 in conjunctiva. Conclusions: Topical
      application of MZR could alleviate epithelial damage and CD4+ T-cell-mediated
      immunity in ocular surface of DED.

PMID- 29204645
TI  - Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human
      Conjunctival Melanoma.
AB  - Purpose: Conjunctival melanoma (CM) is a rare malignant disease that can lead to
      recurrences and metastases. There is a lack of effective treatments for the
      metastases, and we set out to develop a new animal model to test potential
      therapies. Zebrafish are being used as a model for many diseases, and our goal
      was to test whether this animal could be used to study CM. Methods: Three human
      CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM
      2, which has an N-RAS mutation) were injected into the yolk sac, around the eye,
      and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos.
      Fluorescent and confocal images were taken to assess the phenotype and the
      behavior of engrafted cells and to test the effect of Vemurafenib as a treatment
      against CM. Results: While the cells that had been injected inside the yolk sac
      died and those injected around the eye sporadically went into the circulation,
      the cells that had been injected into the duct of Cuvier colonized the zebrafish:
      cells from all three cell lines proliferated and disseminated to the eyes, where
      they formed clusters, and to the tail, where we noticed extravasation and
      micrometastases. Vemurafenib, a potent agent for treatment of B-RAF V600E
      positive melanoma, inhibited outgrowth of CRMM-1 and CM2005.1 cells in a mutation
      dependent way. Conclusions: The (fli:GFP) Casper zebrafish embryo can be used as
      an efficient animal model to study metastatic behavior of human CM cells and
      warrants further testing of drug efficacy to aid care of CM patients.

PMID- 29204646
TI  - A Novel Zebrafish Model for Studying Metastatic Behavior of Human Conjunctival
      Melanoma Cells.

PMID- 29204647
TI  - The Preferred Retinal Locus Used to Watch Videos.
AB  - Purpose: Eccentric viewing is a common strategy used by people with central
      vision loss (CVL) to direct the eye such that the image falls onto functioning
      peripheral retina, known as the preferred retinal locus (PRL). It has been long
      acknowledged that we do not know whether the PRL used in a fixation test is also
      used when performing tasks. We present an innovative method to determine whether
      the same PRL observed during a fixation task was used to watch videos and whether
      poor resolution affects gaze location. Methods: The gaze of a group of 60 normal
      vision (NV) observers was used to define a democratic center of interest (COI) of
      video clips from movies and television. For each CVL participant (N = 20), we
      computed the gaze offsets from the COI across the video clips. The distribution
      of gaze offsets of the NV participants was used to define the limits of NV
      behavior. If the gaze offset was within this 95% degree confidence interval, we
      presumed that the same PRL was used for fixation and video watching. Another 15
      NV participants watched the video clips with various levels of defocus blur.
      Results: CVL participants had wider gaze-offset distributions than NV
      participants (P < 0.001). Gaze offsets of 18/20 CVL participants were outside the
      NV confidence interval. Further, none of the 15 NV participants watching the same
      videos with spherical defocus blur had a gaze offset that was decentered (outside
      the NV confidence interval), suggesting that resolution was not the problem.
      Conclusions: This indicates that many CVL participants were using a PRL to view
      videos that differed from that found with a fixation task and that it was not
      caused by poor resolution alone. The relationship between these locations needs
      further investigation.

PMID- 29204648
TI  - AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro.
AB  - Purpose: Pathologic angiogenesis is a component of many diseases, including
      neovascular age-related macular degeneration, proliferation diabetic retinopathy,
      as well as tumor growth and metastasis. The purpose of this project was to
      examine whether the system of adeno-associated viral (AAV)-mediated CRISPR
      (clustered regularly interspaced short palindromic repeats)-associated
      endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2)
      in human vascular endothelial cells in vitro and thus suppress its downstream
      signaling events. Methods: The dual AAV system of CRISPR/Cas9 from Streptococcus
      pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary
      human retinal microvascular endothelial cells (HRECs). In this system, the
      endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was
      cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of
      green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors
      were applied to production of recombinant AAV serotype 5 (rAAV5), which were used
      to infect HRECs for depletion of VEGFR2. Protein expression was determined by
      Western blot; and cell proliferation, migration, as well as tube formation were
      examined. Results: AAV5 effectively infected vascular endothelial cells (ECs) and
      retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of
      GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5
      CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation
      of Akt, and proliferation, migration as well as tube formation of HRECs.
      Conclusions: AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential
      therapeutic strategy for pathologic angiogenesis.

PMID- 29204650
TI  - Reducing the Underimmunization of Transplant Recipients.

PMID- 29204649
TI  - AAV2-Mediated Transduction of the Mouse Retina After Optic Nerve Injury.
AB  - Purpose: Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful
      therapeutic for the rescue and regeneration of these cells after optic nerve
      damage. However, early after damage, RGCs undergo atrophic changes, including
      gene silencing. It is not known if these changes will deleteriously affect
      transduction and transgene expression, or if the therapeutic protein can
      influence reactivation of the endogenous genome. Methods: Double-transgenic mice
      carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the
      proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs
      still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to
      4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of
      AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by
      expression of the tdTomato reporter. Immunostaining was used to localize tdTomato
      expression in select cell types. Results: Successful transduction of RGCs was
      achieved at all time points after ONC using AAV2 expressing Cre from the
      phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an
      increase in the transduction of cell types in the inner nuclear layer, including
      Muller cells and rod bipolar neurons. There was minimal evidence of transduction
      of amacrine cells and astrocytes in the inner retina or optic nerve. Conclusions:
      Damaged RGCs can be transduced and at least some endogenous genes can be
      subsequently activated. Optic nerve damage may change retinal architecture to
      allow greater penetration of an AAV2 virus to transduce several additional cell
      types in the inner nuclear layer.

PMID- 29204652
TI  - Effect of Nasal Continuous Positive Airway Pressure on Infants With Meconium
      Aspiration Syndrome: A Randomized Clinical Trial.
AB  - Importance: Nasal continuous positive airway pressure (NCPAP) as a primary
      respiratory therapy in meconium aspiration syndrome (MAS) has not been studied
      extensively. Nasal continuous positive airway pressure, when applied in newborns
      with MAS, may resolve atelectasis by sufficiently expanding partially obstructed
      small airways and stabilizing the collapsing terminal airways to enhance oxygen
      exchange. Objective: To compare NCPAP vs standard care in neonates with moderate
      to severe respiratory failure due to MAS in reducing the need for invasive
      ventilation. Design, Settings, and Participants: This multicenter open-label,
      parallel-group (1:1 ratio) randomized clinical trial was conducted from August 5,
      2014, to May 26, 2016. Data were collected from 3 tertiary care neonatal
      intensive care units. All infants admitted with respiratory distress, defined as
      Downe score greater than 4 and peripheral capillary oxygen saturation less than
      90%, were assessed for study eligibility if the chest radiograph was suggestive
      of MAS and they met the other inclusion criteria: gestation longer than 35 weeks,
      a birth weight greater than 2000 g, and born through meconium-stained amniotic
      fluid. Interventions: Infants were randomly assigned to either NCPAP or standard
      care (5-10 L/min hood oxygen). Main Outcomes and Measures: The primary outcome
      was the need for mechanical ventilation in the first 7 days of life. Results:
      After excluding 14 infants, 67 infants were randomized to bubble NCPAP and 68
      infants to standard care. Baseline characteristics were similar between the 2
      groups. Infants randomized to the bubble NCPAP group needed mechanical
      ventilation less frequently in the first 7 days of life compared with standard
      care (2 [3.0%] vs 17 [25.0%]); odds ratio, 0.09; 95% CI, 0.02-0.43; P = .002).
      The need for surfactant (3 [4.5%] vs 11 [16.2%]; odds ratio, 0.24; 95% CI, 0.05
      0.87) and culture-positive sepsis (4 [6.0%] vs 13 [19.0%]; odds ratio, 0.28; 95%
      CI, 0.09-0.93) were higher in the standard care group. There was an increased
      duration of oxygen therapy (median [interquartile range], 45.5 [28.0-78.3] vs 26
      [20.0-48.0] hours; P = .001) in the standard care group. In the NCPAP group vs
      standard care group, incidence of persistent pulmonary hypertension (9 [13%] vs
      19 [28%]; odds ratio, 0.42; 95% CI, 0.17-1.01) and duration of hospital stay
      (median [interquartile range], 5.0 [4.0-8.8] vs 4.0 [4.0-6.0] days; P = .14) were
      similar. Conclusions and Relevance: Bubble NCPAP in comparison with standard care
      for infants with MAS reduces the need for mechanical ventilation in the first 7
      days of life. Trial Registration: Clinical Trial Registry, India Identifier:
      CTRI/2015/03/005631.

PMID- 29204651
TI  - Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.
AB  - Background: The utility of whole-exome sequencing (WES) for the diagnosis and
      management of adult-onset constitutional disorders has not been adequately
      studied. Genetic diagnostics may be advantageous in adults with chronic kidney
      disease (CKD), in whom the cause of kidney failure often remains unknown.
      Objective: To study the diagnostic utility of WES in a selected referral
      population of adults with CKD. Design: Observational cohort. Setting: A major
      academic medical center. Patients: 92 adults with CKD of unknown cause or
      familial nephropathy or hypertension. Measurements: The diagnostic yield of WES
      and its potential effect on clinical management. Results: Whole-exome sequencing
      provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of
      unknown cause and encompassing 13 distinct genetic disorders. Among these, loss
      of-function mutations were identified in PARN in 2 probands with
      tubulointerstitial fibrosis. PARN mutations have been implicated in a short
      telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these
      findings extend the phenotype of PARN mutations to renal fibrosis. In addition,
      review of the American College of Medical Genetics actionable genes identified a
      pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on
      follow-up. The results affected clinical management in most identified cases,
      including initiation of targeted surveillance, familial screening to guide donor
      selection for transplantation, and changes in therapy. Limitation: The small
      sample size and recruitment at a tertiary care academic center limit
      generalizability of findings among the broader CKD population. Conclusion: Whole
      exome sequencing identified diagnostic mutations in a substantial number of
      adults with CKD of many causes. Further study of the utility of WES in the
      evaluation and care of patients with CKD in additional settings is warranted.
      Primary Funding Source: New York State Empire Clinical Research Investigator
      Program, Renal Research Institute, and National Human Genome Research Institute
      of the National Institutes of Health.

PMID- 29204654
TI  - Decreasing Blood Pressure in Older Patients.

PMID- 29204653
TI  - National Patterns of Carotid Revascularization Before and After the Carotid
      Revascularization Endarterectomy vs Stenting Trial (CREST).
AB  - Importance: The Carotid Revascularization Endarterectomy vs Stenting Trial
      (CREST) showed greater safety of carotid artery stenting (CAS) in patients
      younger than 70 years and carotid endarterectomy (CEA) in those older than 70
      years. It is unknown how the result of CREST has influenced carotid
      revascularization choices in the United States. Objective: To evaluate national
      patterns in CAS performance in patients older than 70 years in the post-CREST
      (2011-2014) compared with the pre-CREST (2007-2010) era. Design, Setting, and
      Participants: All adults older than 70 years undergoing carotid revascularization
      in the United States from 2007 to 2014 were retrospectively identified from the
      2007-2014 National Inpatient Sample using International Classification of
      Disease, Ninth Revision procedural codes. From 61 324 882 unweighted
      hospitalizations contained in the 2007-2014 National Inpatient Sample, 494 733
      weighted carotid revascularization admissions in adults older than 70 years were
      identified using International Classification of Disease, Ninth Revision
      procedural codes. Main Outcomes and Measures: The proportion of CAS performed in
      all age groups over time was estimated and multivariable-adjusted models were
      used to compare the odds of receiving CAS in the pre-CREST with those in the post
      CREST era in adults older than 70 years. Results: A total of 41.8% of all
      patients were women, and mean (SE) age at presentation was 78.1 (0.03) years. A
      total of 16.3% of CAS and 10.1% of CEA procedures were performed in patients with
      symptomatic stenosis. The proportion of patients older than 70 years receiving
      CAS increased from 11.9% in the pre-CREST to 13.8% in the post-CREST era (P =
      .005). In multivariable models, the odds of receiving CAS increased by 13% in all
      patients older than 70 years in the post-CREST compared with the pre-CREST period
      (odds ratio [OR], 1.13, 95% CI, 1.00-1.28, P = .04), including symptomatic women
      (OR, 1.31, 1.05-1.65, P = .02). Symptomatic stenosis (OR 1.39; 95% CI, 1.27-1.52;
      P < .001), congestive heart failure (OR, 1.48; 95% CI, 1.35-1.63; P < .001), and
      peripheral vascular disease (OR, 1.35; 95% CI, 1.27-1.43; P < .001) were
      associated with higher odds of CAS; comorbid hypertension (OR, 0.70; 95% CI, 0.66
      0.74; P < .001), smoking (OR, 0.84; 95% CI, 0.78-0.91; P < .001), and weekend
      admission (OR, 0.77; 95% CI, 0.68-0.88; P < .001) were negatively associated with
      the odds of CAS. Conclusions and Relevance: Despite concerns for higher
      periprocedural complications with CAS in elderly patients, the odds of CAS
      increased in the post-CREST compared with pre-CREST era in patients older than 70
      years, including symptomatic women.

PMID- 29204655
TI  - Blood Pressure Trajectories in the 20 Years Before Death.
AB  - Importance: There is mixed evidence that blood pressure (BP) stabilizes or
      decreases in later life. It is also unclear whether BP trajectories reflect
      advancing age, proximity to end of life, or selective survival of persons free
      from hypertension. Objective: To estimate individual patient BP for each of the
      20 years before death and identify potential mechanisms that may explain
      trajectories. Design, Study, and Participants: We analyzed population-based
      Clinical Practice Research Datalink primary care and linked hospitalization
      electronic medical records from the United Kingdom, using retrospective cohort
      approaches with generalized linear mixed-effects modeling. Participants were all
      available individuals with BP measures over 20 years, yielding 46 634
      participants dying aged at least 60 years, from 2010 to 2014. We also compared BP
      slopes from 10 to 3 years before death for 20 207 participants who died, plus 20
      207 birth-year and sex-matched participants surviving longer than 9 years. Main
      Outcomes and Measures: Clinically recorded individual patient repeated systolic
      BP (SBP) and diastolic BP (DBP). Results: In 46 634 participants (51.7% female;
      mean [SD] age at death, 82.4 [9.0] years), SBPs and DBPs peaked 18 to 14 years
      before death and then decreased progressively. Mean changes in SBP from peak
      values ranged from -8.5 mm Hg (95% CI, -9.4 to -7.7) for those dying aged 60 to
      69 years to -22.0 mm Hg (95% CI, -22.6 to -21.4) for those dying at 90 years or
      older; overall, 64.0% of individuals had SBP changes of greater than -10 mm Hg.
      Decreases in BP appeared linear from 10 to 3 years before death, with steeper
      decreases in the last 2 years of life. Decreases in SBP from 10 to 3 years before
      death were present in individuals not treated with antihypertensive medications,
      but mean yearly changes were steepest in patients with hypertension (-1.58; 95%
      CI, -1.56 to -1.60 mm Hg vs -0.70; 95% CI, -0.65 to -0.76 mm Hg), dementia (
      1.81; 95% CI, -1.77 to -1.87 mm Hg vs -1.41; 95% CI, -1.38 to -1.43 mm Hg), heart
      failure (-1.66; 95% CI, -1.62 to -1.69 mm Hg vs -1.37; 95% CI, -1.34 to -1.39 mm
      Hg), and late-life weight loss. Conclusions and Relevance: Mean SBP and DBP
      decreased for more than a decade before death in patients dying at 60 years and
      older. These BP decreases are not simply attributable to age, treatment of
      hypertension, or better survival without hypertension. Late-life BP decreases may
      have implications for risk estimation, treatment monitoring, and trial design.

PMID- 29204656
TI  - Readmissions After Revascularization Procedures for Peripheral Arterial Disease:
      A Nationwide Cohort Study.
AB  - Background: Limited data suggest high rates of unplanned rehospitalization after
      endovascular and surgical revascularization for peripheral arterial disease.
      However, the overall burden of readmissions has not been comprehensively
      explored. Objective: To evaluate nationwide readmissions after peripheral
      arterial revascularization for peripheral arterial disease and to assess whether
      readmission risk varies among hospitals. Design: Retrospective cohort study.
      Setting: 1085 U.S. acute care hospitals participating in the Nationwide
      Readmissions Database. Patients: 61 969 unweighted hospitalizations of patients
      with peripheral arterial disease who had peripheral arterial revascularization
      and were discharged alive between 1 January and 30 November 2014. Measurements:
      30-day readmission rates, causes, and costs of unplanned rehospitalizations after
      peripheral arterial revascularization; 30-day risk-standardized readmission rates
      (RSRRs), calculated using hierarchical logistic regression, to assess for
      heterogeneity of readmission risk between hospitals. Results: Among 61 969
      hospitalizations of patients with peripheral arterial disease who were discharged
      alive after peripheral arterial revascularization, the 30-day nonelective
      readmission rate was 17.6%. The most common cause of readmission was procedural
      complications (28.0%), followed by sepsis (8.3%) and complications due to
      diabetes mellitus (7.5%). Among rehospitalized patients, 21.0% underwent a
      subsequent peripheral arterial revascularization or lower extremity amputation,
      4.6% died, and the median cost of a readmission was $11 013. Thirty-day RSRRs
      varied from 10.0% to 27.3% (interquartile range, 16.6% to 18.8%). Limitation:
      Inability to distinguish out-of-hospital deaths after discharge and potential
      misclassification bias due to use of billing codes to ascertain diagnoses and
      interventions. Conclusion: More than 1 in 6 patients with peripheral arterial
      disease who undergo peripheral arterial revascularization have unplanned
      readmission within 30 days, with high associated mortality risks and costs.
      Procedure- and patient-related factors were the primary reasons for readmission.
      Readmission rates varied moderately between institutions after hospital case mix
      was accounted for, suggesting that differences in hospital quality may only
      partially account for readmission. Primary Funding Source: Smith Center for
      Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center.

PMID- 29204657
TI  - Association Between Physicians' Experiences With Members of Their Social Network
      and Efforts to Reduce Breast Cancer Screening.

PMID- 29204658
TI  - An Ode to Intern Year.

PMID- 29204659
TI  - Bidirectional Associations Between Child Sleep Problems and Internalizing and
      Externalizing Difficulties From Preschool to Early Adolescence.
AB  - Importance: Although multiple cross-sectional and longitudinal studies have
      established that sleep problems and behavioral difficulties are associated in
      children, the directionality of this association and whether sleep problems are
      differentially associated with different types of childhood behavioral
      difficulties are unclear. Understanding these associations will inform the focus
      and timing of interventions. Objective: To determine whether longitudinal and
      reciprocal associations exist between child sleep problems and externalizing,
      internalizing, or both behavioral difficulties. Design, Setting, and
      Participants: Prospective cohort study using nationally representative data from
      the first 5 waves (2004, 2006, 2008, 2010, and 2012) of the kindergarten cohort
      (4983 children aged 4-5 years in 2004) collected for the Longitudinal Study of
      Australian Children. Associations were evaluated using cross-lagged structural
      equation model analyses performed from May 25, 2016, to September 20, 2017. Main
      Outcomes and Measures: Child sleep problems and internalizing and externalizing
      behavioral difficulties. Sleep problems were defined using parent-reported child
      sleep problem severity and specific difficulties (ie, difficulty getting to sleep
      at night, not happy sleeping alone, waking during the night, and restless sleep)
      on 4 or more nights of the week. Child behavioral difficulties were defined using
      the parent-reported Strengths and Difficulties Questionnaire for externalizing
      difficulties (conduct problems and hyperactivity/inattention subscales) and
      internalizing difficulties (emotional problems subscale). Results: The 4983
      children enrolled in 2004 had a mean (SD) age of 4.7 (0.2) years and comprised a
      similar percentage of boys (2536 [50.9%]) and girls. In 2012, 3956 children
      (79.4%) aged 12 to 13 years were retained. Significant bidirectional associations
      were detected between sleep problems and externalizing difficulties during the
      elementary school transition period, with greater sleep problems associated with
      later externalizing behavior and vice versa (cross-lagged path coefficient, 0.04
      [95% CI, 0.01-0.08] to 0.09 [95% CI, 0.06-0.13]). Although sleep was a
      significant driver of later internalizing difficulties (coefficient, 0.10 [95%
      CI, 0.07-0.14] to 0.16 [95% CI, 0.12-0.19]), the reverse association was not
      significant. In the final model that included all 3 constructs, the associations
      were attenuated but remained significant over time. Conclusions and Relevance:
      These results suggest that future studies should investigate whether implementing
      sleep problem intervention decreases the occurrence of both externalizing and
      internalizing difficulties. Interventions targeting externalizing, but not
      internalizing, difficulties may benefit childhood sleep.

PMID- 29204660
TI  - Association of Age With Risk of Hospitalization for Respiratory Syncytial Virus
      in Preterm Infants With Chronic Lung Disease.
AB  - Importance: It is unknown whether the age threshold (<=24 months) for preterm
      infants with chronic lung disease (CLD) to receive immunoprophylaxis for
      respiratory syncytial virus (RSV) as currently recommended by American Academy of
      Pediatrics guidelines correctly identified infants at higher risk for
      hospitalization for RSV. Objective: To determine the age when the risk of
      hospitalization for RSV among preterm infants with CLD becomes equivalent to the
      risk for healthy, 1-month-old term infants who do not qualify for
      immunoprophylaxis. Design, Setting, and Participants: A retrospective cohort
      study was conducted of 1 018 593 healthy term infants and 5181 preterm infants
      with CLD using Medicaid billing records (Medicaid Analytic eXtract files) from
      January 1, 1999, to December 31, 2010, linked to Florida and Texas birth and
      death certificates. Exposures: Age-trend discrete time logistic regression models
      within a survival analysis framework were developed, adjusting for covariates
      including the use of immunoprophylaxis, to compare the risk of hospitalization of
      preterm infants (<32 weeks' gestational age) with CLD at 3 through 34 months of
      age with the risk of hospitalization of term infants (37-41 weeks' gestational
      age) at 1 month of age. Main Outcomes and Measures: Age at which risk of
      hospitalization for RSV among preterm infants with CLD equals the risk for
      healthy term infants at age 1 month. Results: The study cohort included 1 018 593
      healthy term infants and 5181 preterm infants with CLD; because patients could
      reenter the cohort for a second or third season, the total study cohort consisted
      of 1 880 531 healthy term infant-seasons (926 206 girls and 954 325 boys; mean
      [SD] age at first season entry, 12.6 [9.6] months) and 8680 CLD infant-seasons
      (3519 girls and 5161 boys; mean [SD] age at first season entry, 15.1 [9.1]
      months). Among term infants with siblings, the risk of hospitalization for RSV
      averaged across all covariate strata was 9.0 (95% CI, 8.4-9.6) per 1000 patient
      season-months at 1 month of age. The risk of hospitalization for RSV among
      preterm infants with CLD became similar to that of 1-month-old term infants at an
      age of 18.5 months (95% CI, 15.6-22.8). Conclusions and Relevance: The age
      threshold at which the risk of hospitalization for RSV among qualifying preterm
      infants with CLD approximates that of healthy term infants supports the current
      American Academy of Pediatrics practice guideline recommending RSV prophylaxis
      until a maximum of 24 months of age.

PMID- 29204661
TI  - Informing vs Changing the Practice of Carotid Revascularization.

PMID- 29204662
TI  - Vasopressors for acute myocardial infarction complicated by cardiogenic shock.
AB  - Several international evidence-based guidelines reveal the lack of evidence on
      the treatment of patients with acute myocardial infarction (AMI) complicated by
      cardiogenic shock (CS) for all recommended therapies. We included 6 studies with
      842 eligible patients and one ongoing study. Three different adrenergic agents
      (norepinephrine, dopamine, epinephrine), vasopressin and the NOS inhibitor
      tilarginine were compared in 4 different combinations. On the small basis of all
      available evidence we can state that there is no evidence to use tilarginene,
      some evidence to avoid dopamine due to increased rates of arrhythmias, but some
      evidence, which suggests to prefer norepinephrine in comparison to epinephrine as
      vasopressor.

PMID- 29204663
TI  - ["Under pressure": massive tongue swelling after cardiac arrest].

PMID- 29204664
TI  - [Central and peripheral aspects of noise-induced hearing loss].
AB  - Noise is an important socioeconomic problem in industrialized countries.
      Development of efficient treatment options for the audiological phenomena
      resulting from noise-induced hearing loss requires in-depth understanding of the
      underlying damage mechanisms causing peripheral and central nervous changes.
      Mechanical damage, ischemia and excitotoxicity are mainly responsible for noise
      induced cell death and biophysical changes in the cochlea. Auditory synaptopathy
      is an additional consequence. Besides these cochlear pathologies, noise exposure
      leads to extensive changes within the central auditory pathway. Overstimulation
      causes early cell loss in the ventral cochlear nucleus just after noise exposure,
      which is in accordance with enhancement of apoptotic mechanisms within the
      corresponding timeframe. In contrast to the cell loss in lower auditory
      structures due to overstimulation, the later significant reduction of cell
      density in higher auditory structures is due to sensory deprivation. Changes in
      network homeostasis seem to partially compensate structural losses by modulation
      of spontaneous activity. However, central nervous processing of auditory
      information is permanently impaired by the neuroplastic changes. Unfortunately,
      the various noise-induced peripheral and central pathologies are difficult to
      treat. New therapeutic approaches are required, particularly for treatment of
      central nervous processing disorders and auditory synaptopathy, which contribute
      to audiological phenomena such as tinnitus, hyperacusis and poor speech
      perception in noise.

PMID- 29204665
TI  - [Cochlear implants in the social courts].
AB  - BACKGROUND: Since the indication for receiving a cochlear implant (CI) has
      widened (single-sided deafness [SSD], electric acoustic stimulation [EAS],
      bilateral CI, CI for long-term deafness), more and more patients come into
      consideration for such a treatment. Hence, disputes increasingly arise between
      patients and their insurance companies concerning the question of whether surgery
      and follow-up treatment have to be paid for by statutory health insurance.
      OBJECTIVE: This work provides an overview of judgments rendered by the German
      social courts. We investigated whether and in which cases it is advisable for a
      patient to go to court, and how long the proceedings may take. MATERIALS AND
      METHODS: We looked for judgments in the two biggest commercial legal databases
      and in the database of the German social courts, using combinations of the search
      parameters "Cochlear," "Cochlea," "Implant," and "Implantat." Three verdicts were
      attained by directly contacting the court; another one was mentioned in an
      article. The reviewed judgements were issued between 2003 and 2017. RESULTS: A
      total of 12 judgments were found. The patients won in all but one of the main
      proceedings. The case that was lost concerned exceptional circumstances. One
      patient didn't get the desired interim measure, but won in the main proceedings.
      The proceedings took between 1 year and 8 months, and 9 years and 5 months.
      CONCLUSION: Despite the amount of time the patient has to invest, taking legal
      action is worthwhile. The proceedings at the social courts are generally exempt
      from charges. In most cases, the statutory health insurance is ordered to pay for
      a CI.

PMID- 29204666
TI  - Glucerabacter canisensis gen. nov., sp. nov., isolated from dog feces and its
      effect on the hydrolysis of plant glucosylceramide in the intestine of dogs.
AB  - A Gram-positive, obligately anaerobic, oval-rod shaped, non-spore-forming, and
      non-pigmented bacterium, designated strain NATH-2371T (= JCM31739T = DSM105698T),
      was isolated from dog feces. Comparative 16S rRNA gene sequence analysis revealed
      that strain NATH-2371T belongs to Clostridium cluster XIVa, and the closest
      strains were Coprococcus comes ATCC 27758T (94.8% 16S rRNA gene sequence
      similarity) and Clostridium nexile DSM 1787T (94.0%). Strain NATH-2371T produced
      acetate, formate, and ethanol from glucose. Predominant cellular fatty acids are
      C16:0 and C16:0 DMA. On the basis of the phenotypic and genotypic differences,
      strain NATH-2371T represents a novel species in a new genus of the family
      Lachnospiraceae, for which the name Glucerabacter canisensis gen. nov., sp. nov.,
      is proposed. This strain was found to efficiently hydrolyze plant
      glucosylceramide (GluCer). The abundance of strain NATH-2371T in dog feces was
      higher in young dogs than in old dogs. Incubation of dog fecal bacteria showed
      that GluCer-hydrolyzing activity decreased with the age of dogs. The cell number
      of strain NATH-2371T in dog feces appeared to be correlated with GluCer
      hydrolysis. Thus, this bacterium is likely to play a major role in GluCer
      hydrolysis in the dog intestine.

PMID- 29204667
TI  - Correction to: Soluble CD163, adiponectin, C-reactive protein and progression of
      dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the
      ADDITION-PRO cohort.
AB  - The authors have discovered a coding error in the statistical analysis syntax
      file used for the mixed-effect model analyses in this paper. The error has led to
      differences (first decimal) in the estimates for the main results.

PMID- 29204668
TI  - Modification of the Surgical Strategy for the Dissection of the Recurrent
      Laryngeal Nerve Using Continuous Intraoperative Nerve Monitoring.

PMID- 29204669
TI  - [The use of platelet aggregation inhibitors in the perioperative period].
AB  - Every year 16 million operations are performed in Germany. Many patients take
      platelet aggregation inhibitors as a primary or secondary prevention to reduce
      the risk of cardiovascular events. Especially during the perioperative period,
      this risk reduction is relevant due to an increased risk for cardiac events (in
      approximately 6.2% of operations). As a result of a presumed increased risk of
      bleeding, platelet aggregation inhibitors are often paused perioperatively. Thus,
      doctors must decide on a risk-adapted basis whether the medication can be
      continued perioperatively and, if so, with what risks. If acetylsalicylic acid
      (ASA) treatment is solely used as primary prevention it can be paused during the
      perioperative period, whereas ASA treatment for secondary prevention should only
      be paused for operations within narrow confines. When pausing ASA, a sufficient
      time interval should be maintained before the operation. Furthermore, the ASA
      withdrawal syndrome with an increased predisposition for clotting is an important
      phenomenon to be considered. Additionally, the perioperative handling of dual
      platelet aggregation inhibition needed after coronary stent implantation should
      be addressed. Due to an increased risk for in-stent thrombosis, dual platelet
      aggregation inhibition is only reluctantly paused. Emergency surgery must, if not
      otherwise possible, be carried out even if the dual platelet aggregation
      inhibition is not paused; however, if the risk for intraoperative bleeding is too
      high and the risk of an in-stent thrombosis is lower in comparison, P2Y12
      inhibitors (e.g. clopidogrel) should be paused and the operation carried out
      solely with ASA therapy.

PMID- 29204671
TI  - Adjuvant therapy in acute heart failure.

PMID- 29204670
TI  - Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult
      patients with sepsis/septic shock: a systematic review with meta-analysis and
      trial sequential analysis.
AB  - PURPOSE: Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy
      for sepsis or septic shock that clears circulating endotoxin. Prior trials have
      shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence
      synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult
      patients with sepsis or septic shock. METHODS: We searched for randomized
      controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health
      Technology Assessment Database, CINAHL, "Igaku Chuo Zasshi", the National
      Institute of Health Clinical Trials Register, the World Health Organization
      International Clinical Trials Registry Platform, the University Hospital Medical
      Information Network Clinical Trials Registry, the reference lists of retrieved
      articles, and publications by manufacturers of PMX-HP. The primary outcomes were
      28-day all-cause mortality, the number of patients with at least one serious
      adverse event, and organ dysfunction scores. The GRADE methodology for the
      certainty of evidence was used. RESULTS: Six trials (857 participants; weighted
      mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were
      assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP
      was 1.03 [95% confidence interval (CI) 0.78-1.36; I 2 = 25%; n = 797]. The pooled
      RR for adverse events was 2.17 (95% CI 0.68-6.94; I 2 = 0%; n = 717). Organ
      dysfunction scores over 24-72 h after PMX-HP treatment did not change
      significantly (standardized mean difference - 0.26; 95% CI - 0.64 to 0.12; I 2 =
      78%; n = 797). The certainty of the body of evidence was judged as low for both
      benefit and harm using the GRADE methodology. CONCLUSIONS: There is currently
      insufficient evidence to support the routine use of PMX-HP to treat patients with
      sepsis or septic shock. REGISTRATION: PROSPERO International Prospective Register
      of Systematic Reviews (CRD42016038356).

PMID- 29204672
TI  - Bone Loss in Rheumatoid Arthritis: Basic Mechanisms and Clinical Implications.
AB  - Patients with rheumatoid arthritis (RA) have historically developed progressive
      damage of articular bone and cartilage, which correlates with disability over
      time. In addition, these patients are prone to periarticular and systemic bone
      loss, carrying additional morbidity. In contrast to what is seen in many other
      rheumatic diseases, the impact of inflammation on bone in RA is uniquely
      destructive. Loss of articular bone (erosions) and periarticular bone
      (demineralization) is a result of excessive bone resorption and markedly limited
      bone formation. There has been tremendous progress in preventing net bone loss in
      RA with the advent of disease-modifying agents, including biologic agents and
      small molecules, that both limit inflammation and may have a direct impact on the
      prevention of cytokine- and antibody-driven osteoclastogenesis. However, repair
      of existing bone erosions, although feasible, is observed infrequently. Lack of
      repair is a consequence of suppression of osteoblast function and bone formation
      by some of the same mechanisms that promote osteoclastogenesis and bone
      resorption. As new agents are introduced to control inflammation in RA, and novel
      mechanisms to target synovitis are identified, it may be possible in the future
      to fully repair damaged bone.

PMID- 29204673
TI  - The Role of Autoantibodies in Bone Metabolism and Bone Loss.
AB  - Many autoimmune diseases are associated with deranged bone metabolism. The
      resulting localized or systemic bone loss can compromise the quality of life of
      patients by causing local bone deformities or fragility fractures. There is
      emerging evidence that antibodies have a direct impact on key players of bone
      homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide
      insight into the function of autoantibodies related to Rheumatoid Arthritis
      (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated
      protein antibodies) and their inflammation-independent interaction with bone
      cells. Furthermore, we summarize the current knowledge about neutralizing
      antibodies to the antiresorptive protein osteoprotegerin, which have been
      described in patients with Coeliac Disease, Rheumatoid Arthritis, and
      Spondyloarthritis.

PMID- 29204674
TI  - Black Truffle Harvesting in Spanish Forests: Trends, Current Policies and
      Practices, and Implications on its Sustainability.
AB  - The European black truffle is a mycorrhizal fungus native to Spanish
      Mediterranean forests. In most Spanish regions it was originally commercially
      harvested in the second half of the 20th century. Experts agree that wild truffle
      yields suffered a sharp decline during the 1970s and 1980s. However, official
      statistics for Spanish harvest are scarce and seemingly conflicting, and little
      attention has been paid to the regime for the exploitation of truffle-producing
      forests and its implications on the sustainability of this resource. Trends in
      harvest from 1969 to 2013 and current harvesting practices were analyzed as a
      case study, taking into account that Spain is a major truffle producer worldwide,
      but at the same time truffles have only recently been exploited. The available
      statistical sources, which include an increasing proportion of cultivated
      truffles since the mid-1990s, were explored, with estimates from Truffle
      Harvesters Federation showing higher consistency. Statistical sources were then
      compared with proxies for wild harvest (rents from truffle leases in public
      forests) to corroborate time trends in wild harvesting. Results suggest that
      black truffle production is recovering in recent years thanks to plantations,
      whereas wild harvest is still declining. The implications of Spanish legal and
      institutional framework on sustainability of wild truffle use are reviewed. In
      the current scenario, the decline of wild harvest is likely to continue and
      eventually make commercial harvesting economically unattractive, thus aggravating
      sustainability issues. Strengthening of property rights, rationalization of
      harvesting pressure, forest planning and involvement of public stakeholders are
      proposed as corrective measures.

PMID- 29204676
TI  - Surgical management in acute diverticulitis and its association with multi
      detector CT, modified Hinchey classification, and clinical parameters.
AB  - PURPOSE: To assess whether CT findings, clinical parameters, and modified Hinchey
      classification are predictive of management outcomes of patients with acute
      diverticulitis. MATERIALS AND METHODS: Data were accrued between January 2014 and
      December 2015. A total of 301 adult subjects were identified from radiology
      reports, of which six who did not met the inclusion criteria were excluded, thus
      yielding 295 subjects. Subjects were 43.1% (n = 127) male and 56.9% female (n =
      168), with mean age 51.9 years (range 18-90). Two independent abdominal
      radiologists reviewed all scans; imaging features and a modified Hinchey
      classification were scored. Descriptive statistics compared the relationships
      between imaging findings, clinical parameters obtained from medical record
      review, and modified Hinchey classification with management outcomes. RESULTS: CT
      findings associated with surgical management include the presence of a
      pericolonic fluid collection (36.8% vs. 8.2%, P = 0.0001), colonic fistula (13.2%
      vs. 0.4%, P = 0.0002), extraluminal air (26.4% vs. 9.3%, P = 0.0052), bowel
      obstruction (5.2% vs. 0.0%, P = 0.0162), and a modified Hinchey score of Ib or
      higher (55.3% vs. 11.7%, P = 0.0001). Slightly lower systolic blood pressure was
      also associated with operative management (137.2 mmHg vs. 128.2 mmHg, P =
      0.0220). CONCLUSION: Specific CT imaging features and modified Hinchey
      classification are associated with subsequent surgical management in patients
      with acute diverticulitis.

PMID- 29204675
TI  - Resting Stage of Plankton Diversity from Singapore Coastal Water: Implications
      for Harmful Algae Blooms and Coastal Management.
AB  - Resting strategies of planktonic organisms are important for the ecological
      processes of coastal waters and their impacts should be taken into consideration
      in management of water bodies used by multiple industries. We combined different
      approaches to evaluate the importance of resting stages in Singapore coastal
      waters. We used molecular approaches to improve the knowledge on Singapore
      biodiversity, we sampled and extracted cysts from sediments to evaluate the
      density of resting stages in Johor Strait, and we compared systematically
      information on Singapore planktonic biodiversity to existing published
      information on resting stages from these reported organisms. This is the first
      study evaluating the importance of resting stages in Singapore waters. Above 120
      species reported in Singapore are known to produce resting stages though no
      previous work has ever been done to evaluate the importance of these strategies
      in these waters. The results from the resting stage survey confirmed 0.66 to 5.34
      cyst g-1 dry weight sediment were present in the Johor Strait suggesting that
      cysts may be flushed by tidal currents into and out of the strait regularly. This
      also suggest that the blooms occurring in Singapore are likely due to secondary
      growth of Harmful Algae Bloom species in the water rather than from direct
      germination of cysts from sediment. Finally, we discuss the importance of these
      resting eggs for three main national industries in Singapore (shipping, marine
      aquaculture and provision of drinking water through seawater desalination). We
      argue that this study will serve as a baseline for some of the future management
      of Singapore waters.

PMID- 29204677
TI  - The predictive value of quantitative DCE metrics for immediate therapeutic
      response of high-intensity focused ultrasound ablation (HIFU) of symptomatic
      uterine fibroids.
AB  - PURPOSE: The aim of this study was to investigate the value of quantitative DCE
      MRI parameters for predicting the immediate non-perfused volume ratio (NPVR) of
      HIFU therapy in the treatment of symptomatic uterine fibroids. MATERIALS AND
      METHODS: A total of 78 symptomatic uterine fibroids in 65 female patients were
      treated with US-HIFU therapy. All patients underwent conventional MRI and DCE-MRI
      scans 1 day before and 3 days after HIFU treatment. Permeability parameters K
      trans, K ep, V e, and V p and T1 perfusion parameters BF and BV of pretreatment
      were measured as a baseline, while NPVR was used to assess immediate ablation
      efficiency. Data were assigned to NPVR ? 70% and NPVR < 70% groups. Then, the
      predictive performances of different parameters for ablation efficacy were
      studied to seek the optimal cut-off value, and the length of time to calculate
      the variable parameters in each case was recorded. RESULTS: (1) It was observed
      that the pretreatment K trans, K ep, V e, and BF values of the NPVR ? 70% group
      were significantly lower compared to the NPVR < 70% group (p < 0.05). (2) The
      immediate NPVR was negatively correlated with the K trans, BF, and BV values
      before HIFU treatment (r = - 0.561, - 0.712, and - 0.528, respectively, p < 0.05
      for all). (3) The AUCs of pretreatment K trans, BF, BV values, and K trans
      combined with BF used to predict the immediate NPVR were 0.810, 0.909, 0.795, and
      0.922, respectively (p < 0.05 for all). (4) The mean time to calculate the
      variable parameters in each case was 7.5 min. CONCLUSION: Higher K trans, BF, and
      BV values at baseline DCE-MRI suggested a poor ablation efficacy of HIFU therapy
      for symptomatic uterine fibroids, while the pretreatment DCE-MRI parameters could
      be useful biomarkers for predicting the ablation efficacy in select cases. The
      software used to calculate DCE-MRI parameters was simpler, quicker, and easier to
      incorporate into clinical practice.

PMID- 29204678
TI  - Morphological observation and CBCT of the bony canal structure of the groove and
      the location of blood vessels and nerves in the palatine of elderly human
      cadavers.
AB  - PURPOSE: The greater and lesser palatine nerves and vessels supply the hard and
      soft palates, and the roots of these vessels and nerves run through a bony
      structure. However, the arrangement of blood vessels in the maxilla requires
      attention during clinical treatments, but detailed morphological information
      about changes in the greater and lesser palatine arteries and nerves during aging
      is unavailable. We therefore need detailed investigations of the morphology of
      the donor cadaver palatine using cone-beam computed tomography (CBCT) and
      macroscopic observations. METHODS: We investigated 72 donor cadavers using
      macroscopic segmentation and CBCT. The results' analysis examined differences in
      skull measurement parameters and differences between dentate and edentulous
      cases. RESULTS: The greater palatine artery and nerve showed different
      macroscopic arrangements in dentate and edentulous cadavers. We also classified
      three types of bony structures of the nerve and vessel roots in the molar regions
      of the palatine using CBCT images: the shallow groove, deep groove, and flat
      groove. The deep groove is the deepest of the three and is remarkable in
      edentulous elderly cadavers. CONCLUSION: This study of macroscopic and CBCT data
      provides information useful for planning dental implant surgeries and autogenous
      bone harvesting.

PMID- 29204679
TI  - Gestational exposure to inorganic arsenic (iAs3+) alters glutamate disposition in
      the mouse hippocampus and ionotropic glutamate receptor expression leading to
      memory impairment.
AB  - Early life exposure to environmental pollutants and toxic chemicals has been
      linked to learning and behavioral alterations in children. iAs exposure is
      associated with different types neurological disorders such as memory and
      learning impairment. iAs is methylated in the brain by the arsenic III
      methyltransferase in a process that requires glutathione (GSH). The xCT
      antiporter cell membrane transporter participates in the influx of cystine for
      GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice
      gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have
      previously observed up-regulation of xCT in the male mouse hippocampus which
      caused glutamatergic synapse alterations affecting learning and memory processes.
      Here, we used the same gestational iAs exposure model to investigate whether the
      up-regulation of xCT and down-regulation of GLT-1 transporters were associated
      with higher levels of extracellular glutamate and changes in the expression of
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate
      receptor, responsible for excitatory fast synaptic transmission. The induction of
      LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also
      studied, as well as learning and memory formation using the water maze test.
      Changes in GSH levels were also tested in the hippocampus of animals exposed to
      iAs. Results showed increased GSH synthesis (p < 0.05), associated with
      significantly higher extracellular glutamate levels in iAs exposed mice. Exposure
      was also significantly associated with AMPA subunits down-regulation, deficient
      LTP induction, and lower excitability of the PP-DG pathway. In addition, animals
      showed deficient learning and memory in the Morris Water Maze test.

PMID- 29204680
TI  - Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and
      susceptibility to benzene-induced hematotoxicity.
AB  - Occupational exposure to benzene has been associated with leukemia, anemia,
      leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in
      humans may be related to variations in benzene metabolizing genes. The main
      objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1,
      GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of
      benzene among employees of a petrochemical plant. In this cross-sectional study,
      124 employees of a petrochemical plant who had been occupationally exposed to
      benzene and had one or more abnormal hematological parameter (cases) and 184
      subjects with a similar exposure scenario, free from any abnormal hematological
      parameters (referent) were studied. Atmospheric concentrations of benzene were
      measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex
      polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1
      genotypes were determined by PCR- restriction fragment length polymorphism (PCR
      RFLP). The frequency of null GSTT1 genotype in cases was significantly higher
      than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p =
      0.004). The mean value of platelets in subjects with null GSTT1 genotype was
      significantly lower than that of individuals with positive GSTT1 genotype (p =
      0.015). Conversely, the mean value of leukocytes was significantly higher in
      subjects with null GSTM1 genotype as compared to those with positive GSTM1
      genotype (p = 0.026). Logistic regression analysis showed that, subjects with
      null GSTT1 genotype had a significantly higher risk for hematological disorders,
      as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56).
      Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly
      higher risk for hematological disorders as compared to subjects with positive
      GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study
      showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1
      genotypes had a higher risk and were more susceptible to benzene-induced
      hematological disorders.

PMID- 29204682
TI  - Pharmacist-led intervention in the multidisciplinary team approach optimizes
      heart failure medication.
AB  - We evaluated the impact of pharmacist-led heart failure (HF) drug recommendations
      during hospitalization for hospitalized patients with HF. Hospitalized patients
      with HF were retrospectively reviewed. Patients were hospitalized before (n =
      208, non-intervention group) or after (n = 170, intervention group) the launch of
      the HF multidisciplinary team (HFMDT) approach with pharmacist-led HF medication
      optimization. There were no significant group differences in patient background
      characteristics at admission. Patients with HF with reduced ejection fraction who
      were not on beta blockers or angiotensin-converting enzyme inhibitor/angiotensin
      receptor blockers (ACE-I/ARB) at admission were significantly more likely to be
      on beta blockers at the time of discharge in the intervention group (73.3 vs
      96.3%, P = 0.027) compared to those in non-intervention group; however, the
      change in ACE-I/ARB prescriptions was not significant (53.3 vs 63.3%, P = 0.601).
      The proportion of patients on any drug with recommendations against its use in
      patients with HF did not change from admission to discharge in the non
      intervention group (21.2 vs. 20.2%, P = 0.855), but was significantly reduced in
      the intervention group (22.9 vs. 12.9%, P = 0.005). There were no group
      differences in the in-hospital all-cause mortality (non-intervention, 3.4%;
      intervention, 2.4%; P = 0.761) or length of hospital stay (median: non
      intervention, 13 days; intervention, 14 days; P = 0.508). Pharmacist-led HF drug
      recommendations during hospitalization as part of a HFMDT approach for
      hospitalized patients with HF can increase beta blocker prescriptions and
      decrease non-preferred drug prescriptions.

PMID- 29204683
TI  - Wide difference in biologics usage and expenditure for the treatment of patients
      with rheumatoid arthritis in each prefecture in Japan analyzed using "National
      Database of Health Insurance Claims and Specific Health Checkups of Japan".
AB  - To analyze the biologics usage and expenditure for the treatment of patients with
      rheumatoid arthritis (RA) in each prefecture throughout Japan using the national
      open database, the Ministry of Health, Labour and Welfare of Japan disclosed; in
      Oct 2016, the data of the top 30 most-frequently prescribed drugs during a 1-year
      period from April 2014 to March 2015 in each prefecture in Japan, along with the
      patients' age and sex. Seldom-used drugs were excluded. We picked up only
      biologics for the present study. The total expenditure on biologics used in each
      prefecture was correlated with the population thereof. However, there was a big
      difference, up to ~ twofold, in the average expenditure used for an RA patient:
      highest in Toyama and lowest in Wakayama. There was also a big difference, ~ 4.5
      fold, in the number of rheumatologists/1000 RA patients, highest in Kyoto and
      lowest in Aomori. The average expenditure used for an RA patient was correlated
      with the number of rheumatologists in the western part of Japan. Etanercept
      seemed to be used most frequently to Japanese RA patients followed closely by
      infliximab. Abatacept was used more frequently to the elderly than other
      biologics. There was a big difference in the number of rheumatologists and
      expenditure on biologics for the treatment of an RA patient among prefectures in
      fiscal 2014. Factors that brought this unevenness need to be scrutinized for
      universal implementation of good RA care throughout Japan, where there are
      uniform health insurance system and free access to rheumatologists.

PMID- 29204684
TI  - DNA methylation of the CDC2L1 gene promoter region decreases the expression of
      the CDK11p58 protein and reduces apoptosis in keloid fibroblasts.
AB  - The excessive growth of fibroblasts in keloid is closely related to the status of
      gene methylation. The aim of this project was to study whether keloid development
      is related to DNA methylation in the CDC2L1 gene promoter region. DNA methylation
      of the promoter of this gene was analyzed by bisulfite sequencing and verified by
      DNA methylation-specific polymerase chain reaction. The results showed that the
      DNA methylation rate of CpG islands in the CDC2L1 gene promoter region was 50.0%
      (12/24) in patient keloid tissues and 0% (0/24) in normal skin-tissues from
      healthy controls. Patient keloid tissues with (n = 12) DNA methylation of the
      CDC2L1 gene promoter showed higher growth rates than those without (n = 12).
      Samples from keloid tissues with DNA methylation of the CDC2L1 gene promoter
      region had dramatically lower levels of CDK11p58 protein than samples from keloid
      tissues without DNA methylation of the CDC2L1 gene promoter region or healthy
      normal skin-tissues. In the fibroblasts with DNA methylation of the CDC2L1 gene
      promoter region from keloid tissues treated with DNA methyl-transferase inhibitor
      5 aza 2'-deoxycytidine (5-aza-dC) for 48 h, CDK11p58 levels in the fibroblasts
      were significantly increased in a dose-dependent manner; the apoptotic rate of
      the fibroblasts was significantly higher in the treated group than in the non
      treated group. This study revealed that DNA methylation exists in the CDC2L1 gene
      promoter region in keloid tissue fibroblasts. DNA methylation of the CDC2L1 gene
      promoter region dramatically inhibits the expression of CDK11p58 protein in
      keloid tissues. A specific demethylation drug, 5-aza-dC, suppressed DNA
      methylation of the promoter region, which increased the expression of CDK11p58.
      The elevated expression of CDK11p58 resulted in increased fibroblast apoptosis,
      thus restraining the development of keloids.

PMID- 29204681
TI  - [S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis].

PMID- 29204685
TI  - Methylene Blue Protects the Isolated Rat Lungs from Ischemia-Reperfusion Injury
      by Attenuating Mitochondrial Oxidative Damage.
AB  - INTRODUCTION: Impaired mitochondrial function is a key factor attributing to the
      lung ischemia reperfusion injury (LIRI). Methylene blue (MB) has been reported to
      attenuate brain and renal ischemia-reperfusion injury. We hypothesized that MB
      also could have a protective effect against LIRI by preventing mitochondrial
      oxidative damage. METHODS: Isolated rat lungs were assigned to the following four
      groups (n = 6): a sham group: perfusion for 105 min without ischemia; I/R group:
      shutoff of perfusion and ventilation for 45 min followed by reperfusion for 60
      min; and I/R + MB group and I/R + glutathione (GSH) group: 2 mg/kg MB or 4 MUM
      glutathione were intraperitoneally administered for 2 h, and followed by 45 min
      of ischemia and 60 min of reperfusion. RESULTS: MB lessened pulmonary dysfunction
      and severe histological injury induced by ischemia-reperfusion injury. MB reduced
      the production of reactive oxygen species and malondialdehyde and enhanced the
      activity of superoxide dismutase. MB also suppressed the opening of the
      mitochondrial permeability transition pore and partly preserved mitochondrial
      membrane potential. Moreover, MB inhibited the release of cytochrome c from the
      mitochondria into the cytosol and decreased apoptosis. Additionally, MB
      downregulated the mRNA expression levels of pro-inflammatory cytokines (TNF
      alpha, IL-1beta, IL-6, and IL-18). CONCLUSION: MB protects the isolated rat lungs
      against ischemia-reperfusion injury by attenuating mitochondrial damage.

PMID- 29204687
TI  - A physiologically based pharmacokinetic (PBPK) parent-metabolite model of the
      chemotherapeutic zoptarelin doxorubicin-integration of in vitro results, Phase I
      and Phase II data and model application for drug-drug interaction potential
      analysis.
AB  - PURPOSE: Zoptarelin doxorubicin is a fusion molecule of the chemotherapeutic
      doxorubicin and a luteinizing hormone-releasing hormone receptor (LHRHR) agonist,
      designed for drug targeting to LHRHR positive tumors. The aim of this study was
      to establish a physiologically based pharmacokinetic (PBPK) parent-metabolite
      model of zoptarelin doxorubicin and to apply it for drug-drug interaction (DDI)
      potential analysis. METHODS: The PBPK model was built in a two-step procedure.
      First, a model for doxorubicin was developed, using clinical data of a
      doxorubicin study arm. Second, a parent-metabolite model for zoptarelin
      doxorubicin was built, using clinical data of three different zoptarelin
      doxorubicin studies with a dosing range of 10-267 mg/m2, integrating the
      established doxorubicin model. DDI parameters determined in vitro were
      implemented to predict the impact of zoptarelin doxorubicin on possible victim
      drugs. RESULTS: In vitro, zoptarelin doxorubicin inhibits the drug transporters
      organic anion-transporting polypeptide 1B3 (OATP1B3) and organic cation
      transporter 2 (OCT2). The model was applied to evaluate the in vivo inhibition of
      these transporters in a generic manner, predicting worst-case scenario decreases
      of 0.5% for OATP1B3 and of 2.5% for OCT2 transport rates. Specific DDI
      simulations using PBPK models of simvastatin (OATP1B3 substrate) and metformin
      (OCT2 substrate) predict no significant changes of the plasma concentrations of
      these two victim drugs during co-administration. CONCLUSIONS: The first whole
      body PBPK model of zoptarelin doxorubicin and its active metabolite doxorubicin
      has been successfully established. Zoptarelin doxorubicin shows no potential for
      DDIs via OATP1B3 and OCT2.

PMID- 29204686
TI  - Weather conditions influence the number of psychiatric emergency room patients.
AB  - The specific impact of weather factors on psychiatric disorders has been
      investigated only in few studies with inconsistent results. We hypothesized that
      meteorological conditions influence the number of cases presenting in a
      psychiatric emergency room as a measure of mental health conditions. We analyzed
      the number of patients consulting the emergency room (ER) of a psychiatric
      hospital in Berlin, Germany, between January 1, 2008, and December 31, 2014. A
      total of N = 22,672 cases were treated in the ER over the study period.
      Meteorological data were obtained from a publicly available data base. Due to
      collinearity among the meteorological variables, we performed a principal
      component (PC) analysis. Association of PCs with the daily number of patients was
      analyzed with autoregressive integrated moving average model. Delayed effects
      were investigated using Granger causal modeling. Daily number of patients in the
      ER was significantly higher in spring and summer compared to fall and winter (p <
      0.001). Three PCs explained 76.8% percent of the variance with PC1 loading mostly
      on temperature, PC2 on cloudiness and low pressure, and PC3 on windiness. PC1 and
      PC2 showed strong association with number of patients in the emergency room (p <
      0.010) indicating higher patient numbers on warmer and on cloudy days. Further,
      PC1, PC2, and PC3 predicted the number of patients presenting in the emergency
      room for up to 7 days (p < 0.050). A secondary analysis revealed that the effect
      of temperature on number of patients was mostly due to lower patient numbers on
      cold days. Although replication of our findings is required, our results suggest
      that weather influences the number of psychiatric patients consulting the
      emergency room. In particular, our data indicate lower patient numbers during
      very cold temperatures.

PMID- 29204688
TI  - Pharmacokinetics of recombinant asparaginase in children with acute lymphoblastic
      leukemia.
AB  - PURPOSE: The objective of this study was to assess the pharmacokinetics of
      recombinant asparaginase (rASNase, Spectrila(r)) in children with acute
      lymphoblastic leukemia using a population pharmacokinetic approach in order to
      explore potential dosing recommendations. METHODS: Data on serum asparaginase
      activities of 124 children from three clinical studies were included in the
      analysis, covering an age range from 3 days to 17 years. Most patients received
      5000 U/m2 rASNase intravenously every 3 days. The non-linear mixed effects
      modelling software (NONMEM(r)) was utilized to identify drivers of rASNase
      pharmacokinetics in children. Different dose adjustments were simulated for their
      ability to increase rASNase trough activities in children who do not reach the
      threshold of 100 U/L. RESULTS: A two-compartment model with allometric weight
      scaling (0.75 on clearance [CL] and inter-compartmental clearance [Q] and 1 on
      central [V 1] and peripheral [V 2] volume of distribution) was the best model to
      describe the pharmacokinetics of rASNase. PK parameters for the median child
      (19.5 kg) were: CL = 0.0592 L/h, V 1 = 1.18 L, Q = 0.307 L/h, V 2 = 0.316 L.
      Organ functions, such as liver or kidney function and laboratory values, such as
      fibrinogen or antithrombin III levels, showed no influence on rASNase
      pharmacokinetics. In simulations, changing the administration interval from 72 to
      48 h was appropriate to maintain rASNase activities above the therapeutic
      threshold, in patients with activities below 100 U/L 72 h after the first dose.
      CONCLUSIONS: Drug monitoring is recommended to identify patients with
      insufficient ASNase trough activities in serum and to modify the treatment
      schedule, if necessary. Shortening of the treatment interval might be preferable
      over increasing the rASNase dose.

PMID- 29204689
TI  - Comparison between over-glasses patching and adhesive patching for children with
      moderate amblyopia: a prospective randomized clinical trial.
AB  - PURPOSE: To investigate efficacy of over-glasses patching treatment for amblyopic
      children using visual function improvement and Amblyopia Treatment Index (ATI)
      changes. METHODS: In a randomized multi-center controlled clinical trial, 107
      children aged 3-7 years with moderate amblyopia (visual acuity in the range of
      20/40 to 20/100) were included to receive treatment with either an adhesive skin
      patch or a fabric over-glasses patch. The patients were prescribed 2 h of
      patching per day for the sound eye. Best-corrected visual acuity (BCVA) was
      investigated and ATI questionnaires were collected from parents at 5 weeks and 17
      weeks after the initiation of treatment. ATI identifies barriers and problems
      associated with amblyopia treatment. We compared the changes of visual acuity of
      amblyopic eyes and ATI scores in two groups. RESULTS: At 17 weeks, the mean
      visual acuity of the amblyopic eye using Snellen chart improved 3.2 lines in the
      adhesive patching group and 2.7 lines for an over-glasses patching method that
      fit over eyeglasses (p = 0.345). A similar proportion of subjects in each group
      had improvement of >= 2 lines (adhesive patching group 67% vs over-glasses
      patching group 67%, p = 0.372). There was also no difference in treatment burden
      in each group as measured with the Amblyopia Treatment Index. The only item to
      demonstrate a significant difference between groups was that related to
      "Treatment makes the eye or eyelids red" (mean 4.0 +/- 1.1 vs 3.0 +/- 1.0 at 17
      weeks, p = 0.001, for adhesive vs over-glasses patch). CONCLUSIONS: Over-glasses
      patching treatment is a useful option for amblyopia treatment when the patients
      suffer from adverse effects of using adhesive skin patching.

PMID- 29204691
TI  - First clinical experience of a dedicated irrigated-tip radiofrequency ablation
      catheter for the ablation of cavotricuspid isthmus-dependent atrial flutter.
AB  - BACKGROUND: Different types of irrigated-tip ablation catheters are available for
      ablation of atrial flutter (AFL). The aim of this study was to compare an
      established with a novel dedicated Gold irrigated-tip catheter for ablation of
      AFL. METHODS AND RESULTS: We compared consecutive patients undergoing ablation of
      AFL using a standard 3.5 mm irrigated-tip platinum-iridium (Pt-Ir) catheter
      (Thermocool, TC-group) and a 3.5 mm irrigated gold-tip catheter (Gold-group)
      specifically designed for cavotricuspid isthmus ablation (CTI). The primary
      endpoint was acute efficacy (net RF time) to achieve block across the CTI.
      Secondary endpoints included procedure time, fluoroscopy duration, complications,
      and recurrence of AFL.153 patients (age 68 +/- 11 years, 74% male) were included.
      Net RF time to achieve CTI block was not different between the TC-group (793 +/-
      503 s) and the Gold-group (706 +/- 422 s; p = 0.406). Total procedure time was
      not significantly different between the TC-group (70 +/- 26 min) and the Gold
      group (70 +/- 27 min; p = 0.769). A significant difference between the groups was
      identified for the fluoroscopy duration (TC-group: 934 +/- 537 s, Gold-group: 596
      +/- 362 s, p < 0.001). There were no major complications observed in the groups.
      Recurrence of AFL occurred in 3 of 66 (5%) in the TC-group and in 2 of 87 (2%) in
      the Gold-group (p = 0.652). CONCLUSIONS: In conclusion, acute and chronic
      efficacy of the irrigated Pt-Ir and gold-tip catheters were comparable. However,
      the dedicated catheter design was associated with decreased fluoroscopy duration.

PMID- 29204690
TI  - Fruit and vegetable intake and pre-diabetes: a case-control study.
AB  - PURPOSE: Few studies have evaluated the association of fruit and vegetable (FV)
      intake and pre-diabetes. However, these studies are very limited and incomplete.
      Therefore, the aim of our study was to compare FV consumption and their subgroups
      between pre-diabetic and control subjects. METHODS: This case-control study
      included 300 individuals, 150 subjects with normal fasting blood glucose (FBG),
      and 150 pre-diabetic subjects who were matched for sex and age. We collected the
      participants' anthropometric and physical activity data and measured their blood
      glucose level. A 168 items semi-quantitative food frequency questionnaire (FFQ)
      was used for estimating the FV intake. RESULTS: After adjustment for confounding
      variables, participants in the lower quartiles of FV and total fruit intake were
      more likely to experience pre-diabetes compared with those in the higher
      quartiles (p trend < 0.007). In addition, cruciferous vegetables, other
      vegetables, and berries were inversely associated with pre-diabetes (p < 0.05),
      although a distinct dose-response relationship was not found. Unexpectedly,
      higher intake of dark yellow vegetables was significantly associated with a
      higher chance of pre-diabetes (p trend = 0.006). Other vegetable and fruit
      subgroups did not show any significant relationship with this disorder.
      CONCLUSION: Our findings suggest that higher intake of total FV and total fruits
      might be associated with lower odds ratio of pre-diabetes.

PMID- 29204692
TI  - Flight-induced transgenerational maternal effects influence butterfly offspring
      performance during times of drought.
AB  - Maternal condition can generate resource-related maternal effects through
      differential egg provisioning that can negatively affect offspring performance
      especially when offspring growth occurs in stressful or sub-optimal environments.
      Using the Speckled Wood butterfly, Pararge aegeria (L.) we tested the hypothesis
      that repeated periods of intensive flight during female oviposition affects egg
      provisioning and reduces offspring performance when larval development occurs
      under stressful conditions on drought stressed host plants. We investigated
      whether (after controlling for egg size) maternal age and flight treatment
      resulted in changes in egg provisioning and whether this contributed to variation
      in offspring traits across life stages. Age-related changes in maternal condition
      were found to generate resource-related maternal effects that influenced
      offspring traits across all life stages. Flight-induced changes in maternal egg
      provisioning were found to have direct consequences for offspring development in
      the egg and larval stages. There were significant interactive effects between
      maternal age and flight on larval development and growth. Compared to offspring
      from forced flight mothers, offspring from control (no forced flight) mothers
      that hatched from eggs laid early in the oviposition period (i.e. by younger
      mothers) had shorter larval development times and heavier pupal masses,
      suggesting that offspring from mothers in relatively good condition may be able
      to buffer some of the costs associated with growth on drought stressed host
      plants. Our multi-factor study demonstrates the importance of considering the
      various, and often interacting, mechanisms by which maternal effects may
      influence offspring performance in stressful environments.

PMID- 29204693
TI  - Intensive land use drives small-scale homogenization of plant- and leafhopper
      communities and promotes generalists.
AB  - The current biodiversity decline through anthropogenic land-use not only involves
      local species losses, but also homogenization of communities, with a few
      generalist species benefitting most from human activities. Most studies assessed
      community heterogeneity (beta-diversity) on larger scales by comparing different
      sites, but little is known about impacts on beta-diversity within each site,
      which is relevant for understanding variation in the level of alpha-diversity,
      the small-scale distribution of species and associated habitat heterogeneity. To
      obtain our dataset with 36,899 individuals out of 117 different plant- and
      leafhopper (Auchenorrhyncha) species, we sampled communities of 140 managed
      grassland sites across Germany by quantitative vacuum suction of five 1 m2 plots
      on each site. Sites differed in land-use intensity as characterized by intensity
      of fertilization, mowing and grazing. Our results demonstrate a significant
      within-site homogenization of plant- and leafhopper communities with increasing
      land-use intensity. Correspondingly, density (- 78%) and gamma-diversity (- 35%)
      declined, particularly with fertilization and mowing intensity. More than 34% of
      plant- and leafhopper species were significant losers and only 6% were winners of
      high land-use intensity, with abundant and widespread species being less
      affected. Increasing land-use intensity adversely affected dietary specialists
      and promoted generalist species. Our study emphasizes considerable, multifaceted
      effects of land-use intensification on species loss, with a few dominant
      generalists winning, and an emerging trend towards more homogenized assemblages.
      By demonstrating homogenization for the first time within sites, our study
      highlights that anthropogenic influences on biodiversity even occur on small
      scales.

PMID- 29204694
TI  - IROS 2018.

PMID- 29204695
TI  - Percutaneous Image-Guided Ablation in the Treatment of Osseous Metastases from
      Non-small Cell Lung Cancer.
AB  - INTRODUCTION: Percutaneous image-guided ablation is an emerging minimally
      invasive therapy for patients with metastatic bone disease for whom radiation
      therapy is ineffective or contraindicated. The purpose of this study was to
      examine the safety and efficacy of percutaneous ablation in achieving pain
      palliation and local tumor control of osseous metastases from non-small cell lung
      cancer (NSCLC). METHODS: A retrospective review was performed of 76
      musculoskeletal metastases in 45 patients treated with percutaneous ablation. 63%
      (48/76) were treated with radiofrequency ablation (RFA), 35% (27/76) with
      cryoablation, and 1.3% (1/76) with microwave ablation (MWA). In 70% (53/76) of
      cases, associated cementoplasty was performed. Primary outcomes measured were pre
      and post-procedure pain scores 4 weeks after treatment and local tumor control
      at 3-, 6-, and 12-month follow-up. RESULTS: Mean age of the cohort was 63.6 +/-
      9.5 years. Median tumor diameter was 3.60 cm (range 1.0-10.0 cm). Mean and median
      pain scores before treatment were 7.5 +/- 2.3 and 8.0, respectively. Post
      procedure, patients reported significantly decreased pain scores at 4 weeks
      (mean, 3.7 +/- 3.5; median, 3.0; p < 0.00001). Radiographic local tumor control
      rates were 83% (35/42) at 3 months, 77% (23/30) at 6 months, and 68% (17/25) at
      12 months after treatment. The overall complication rate was 2.6% (2/76).
      CONCLUSION: Percutaneous tumor ablation is a well-tolerated, minimally invasive
      procedure associated with improving pain palliation and achieving local tumor
      control of osseous metastases from NSCLC. LEVEL OF EVIDENCE: Level 4, case
      series.

PMID- 29204696
TI  - Patients' perspective on bowel resection for inflammatory bowel disease.
AB  - PURPOSE: The study aimed to determine whether patients are receiving adequate
      counselling about elective bowel resection and timely surgery for inflammatory
      bowel disease (IBD). METHODS: Patients with IBD who underwent an elective bowel
      resection in a tertiary referral centre between April 2012 and Dec 2014 were
      identified from a prospective database. Patients under the age of 16 years were
      excluded from the study. Patients were contacted over the phone to complete a
      questionnaire regarding their perspective on their surgery, including the
      consultations that took place, preparedness and timing of surgery, as well as
      patient attitude towards bowel resection and satisfaction with post-operative
      outcomes. Demographic details were recorded. RESULTS: Thirty-one patients
      participated in the study. Twenty-one (68%) patients were diagnosed with Crohn's
      disease, nine (29%) were diagnosed with ulcerative colitis, and one (3%) had
      indeterminate colitis. Twenty-seven (87%) patients reported that the timing of
      the initial consultation regarding the option of bowel resection was appropriate.
      Twenty-five (81%) patients felt prepared after a consultation with the surgical
      team with regard to perioperative issues and potential complications. Fourteen
      (45%) patients reported that the timing of bowel resection was appropriate, while
      15 (48%) reported that it should have been earlier. A significant improvement in
      patient's pre- and post-operative attitudes towards bowel resection was
      demonstrated (p = 0.004). Thirty (97%) patients were either happy or very happy
      with their results and symptom improvement post-bowel resection. CONCLUSION: Most
      patients are receiving adequate counselling about elective bowel resection for
      IBD, although there is room for improvement for preoperative education and
      optimising timing of surgery.

PMID- 29204697
TI  - How to reduce the superior mesenteric vein bleeding risk during laparoscopic
      right hemicolectomy.
AB  - PURPOSE: The superior right colic vein (SRCV) has been proposed as the main cause
      of superior mesenteric vein bleeding by avulsion during laparoscopic right
      hemicolectomy. Our objective is to identify the main vessel causing transverse
      mesocolic tension during the extraction of the surgical specimen or
      extracorporeal anastomosis and to perform an anatomical description of the SRCV.
      METHODS: In this cadaveric study, we performed a simulation of right
      hemicolectomy and anatomical description of the surgical area of the gastrocolic
      trunk of Henle (SAGCTH), the gastrocolic trunk of Henle (GCTH), and SRCV. The
      length of the exteriorization of the anastomotic transverse colon (ATC) was
      measured before and after sectioning the vascular vessel causing the
      exteriorization tension. RESULTS: Five fresh cadavers and 12 formalin were
      dissected. In 100% of the specimens, the SRCV was present and drained in 95% into
      the GCTH and in 5% directly into the superior mesenteric vein (SMV). In 100% of
      the specimens, the SRCV caused the tension when extracting the ATC. The mean
      length of exteriorization of the ATC before and after SRCV section was 7.2 and
      10.4 cm in formalin cadavers, meaning a 44% of increment in the length of
      exteriorization. In fresh cadavers, the mean length of exteriorization increased
      to 2.7 cm, meaning a 28% of the initial length of exteriorization. CONCLUSIONS:
      The SRCV is the main cause of tension in the extraction of the surgical specimen
      after right hemicolectomy. Its high tie increases the length of the ATC
      exteriorization, in about 3 cm, and could reduce the risk of SMV bleeding during
      laparoscopic right hemicolectomy and facilitate an extracorporeal anastomosis
      free of tension.

PMID- 29204699
TI  - Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and
      Sezary syndrome.
AB  - Tumor progression is associated with progressive immunosuppression mediated in
      part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s)
      (MDSC). Development of strategies to reduce populations of immune cells with
      suppressive function in cancer patients may enable the induction or recovery of
      immunity against tumor cells, which may limit or reverse disease progression.
      With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis
      fungoides (MF) and Sezary syndrome (SzS), we determined the association between
      disease stage and suppressor cell populations in patients with MF/SzS, including
      those responding to therapy. We found elevations in Treg populations, across Treg
      subtypes, in patients with SzS, and these Treg markedly suppressed proliferation
      of autologous CD4+CD25- responder T cells. Interestingly, while MDSC numbers were
      not increased in MF/SzS patients, MDSC from patients with stage IB and above
      produced significantly more reactive oxygen species than those from stage IA MF
      patients and control cohorts. Therapy with the CD25-targeting agent denileukin
      diftitox or IFN-alpha2b was associated with a reduction in Treg numbers or MDSC
      function, respectively. These studies identify potential mechanisms of action for
      these therapies and support the development of coordinated strategies targeting
      both Treg and MDSC activities in patients with MF/SzS.

PMID- 29204698
TI  - Fumarase is involved in DNA double-strand break resection through a functional
      interaction with Sae2.
AB  - One of the most severe forms of DNA damage is the double-strand break (DSB).
      Failure to properly repair the damage can cause mutation, gross chromosomal
      rearrangements and lead to the development of cancer. In eukaryotes, homologous
      recombination (HR) and non-homologous end joining (NHEJ) are the main DSB repair
      pathways. Fumarase is a mitochondrial enzyme which functions in the tricarboxylic
      acid cycle. Intriguingly, the enzyme can be readily detected in the cytosolic
      compartment of all organisms examined, and we have shown that cytosolic fumarase
      participates in the DNA damage response towards DSBs. In human cells, fumarase
      was shown to be involved in NHEJ, but it is still unclear whether fumarase is
      also important for the HR pathway. Here we show that the depletion of cytosolic
      fumarase in yeast prolongs the presence of Mre11 at the DSBs, and decreases the
      kinetics of repair by the HR pathway. Overexpression of Sae2 endonuclease reduced
      the DSB sensitivity of the cytosolic fumarase depleted yeast, suggesting that
      Sae2 and fumarase functionally interact. Our results also suggest that Sae2 and
      cytosolic fumarase physically interact in vivo. Sae2 has been shown to be
      important for the DSB resection process, which is essential for the repair of
      DSBs by the HR pathway. Depletion of cytosolic fumarase inhibited DSB resection,
      while the overexpression of cytosolic fumarase or Sae2 restored resection.
      Together with our finding that cytosolic fumarase depletion reduces Sae2 cellular
      amounts, our results suggest that cytosolic fumarase is important for the DSB
      resection process by regulating Sae2 levels.

PMID- 29204701
TI  - Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and
      prolongs survival of MUC1.Tg mice challenged with pancreatic tumors.
AB  - A substantial body of evidence suggests the existence of MUC1-specific antibodies
      and cytotoxic T cell activities in pancreatic cancer patients. However, tumor
      induced immunosuppression renders these responses ineffective. The current study
      explores a novel therapeutic combination wherein tumor-bearing hosts can be
      immunologically primed with their own antigen, through opsonization with a tumor
      antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization
      with this antibody in combination with PolyICLC and anti-PD-L1. The therapeutic
      combination of mAb-AR20.5 + anti-PD-L1 + PolyICLC induced rejection of human MUC1
      expressing tumors and provided a long-lasting, MUC1-specific cellular immune
      response, which could be adoptively transferred and shown to provide protection
      against tumor challenge in human MUC1 transgenic (MUC.Tg) mice. Furthermore,
      antibody depletion studies revealed that CD8 cells were effectors for the MUC1
      specific immune response generated by the mAb-AR20.5 + anti-PD-L1 + PolyICLC
      combination. Multichromatic flow cytometry data analysis demonstrated a
      significant increase over time in circulating, activated CD8 T cells, CD3+CD4-CD8
      (DN) T cells, and mature dendritic cells in mAb-AR20.5 + anti-PD-L1 + PolyICLC
      combination-treated, tumor-bearing mice, as compared to saline-treated control
      counterparts. Our study provides a proof of principle that an effective and long
      lasting anti-tumor cellular immunity can be achieved in pancreatic tumor-bearing
      hosts against their own antigen (MUC1), which can be further potentiated using a
      vaccine adjuvant and an immune checkpoint inhibitor.

PMID- 29204702
TI  - Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients
      with advanced non-small cell lung cancers treated with anti-PD-1 antibody.
AB  - We investigated inflammatory markers such as the neutrophil-to-lymphocyte ratio
      (NLR) that may predict the response to anti-PD-1 (programmed cell death protein
      1) antibody therapy. Data from 54 patients with non-small cell lung cancer
      (NSCLC) treated with anti-PD-1 antibodies were retrospectively analyzed. The NLR
      was assessed at baseline and 6 weeks after the start of treatment (post
      treatment). Eighteen of 54 patients (33.3%) had objective responses to treatment.
      Older age, absence of brain metastasis, low post-treatment NLR (< 5), and immune
      related adverse events were significantly associated with response. Patients with
      a high post-treatment NLR (>= 5) had significantly shorter progression-free
      survival (PFS) than those with a low post-treatment NLR (median, 1.3 vs. 6.1
      months, p < 0.001). Multivariate analysis demonstrated that high post-treatment
      NLR [hazard ratio (HR) 15.1, 95% confidence interval (CI) 1.5-50.1, p < 0.001],
      liver metastasis (HR 4.9, 95% CI 1.9-12.4, p = 0.001), and brain metastasis (HR
      3.2, 95% CI 1.3-8.2, p = 0.013) were independent prognostic factors of shorter
      PFS. Overall survival (OS) was significantly different in patients with high and
      low post-treatment NLRs (median, 2.1 vs. 14.0 months, p < 0.001). A high post
      treatment NLR remained an independent prognostic factor for OS in multivariate
      analysis (HR 3.9, 95% CI 1.6-9.2, p = 0.003). The NLR at 6 weeks after treatment
      initiation was a prognostic marker in patients with advanced NSCLC treated with
      anti-PD-1 antibody. Further studies are warranted to evaluate the role of the 6
      week NLR as a predictor in anti-PD-1 antibody treatment.

PMID- 29204700
TI  - The Immunoscore system predicts prognosis after liver metastasectomy in
      colorectal cancer liver metastases.
AB  - BACKGROUND: The Immunoscore was initially established to evaluate the prognosis
      of stage I/II/III colorectal cancer patients. However, the feasibility of the
      Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has
      not been reported. METHODS: Liver metastases in 249 CRCLM patients were
      retrospectively analyzed. The Immunoscore was assessed according to the counts
      and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by
      immunohistochemistry. The prognostic role of the Immunoscore for relapse-free
      survival (RFS) and overall survival (OS) was analyzed with Kaplan-Meier curves
      and Cox multivariate models, and confirmed via an internal validation. Receiver
      operating characteristic (ROC) curves were plotted to compare the prognostic
      values of the Immunoscore and the clinical risk score (CRS) system. RESULTS:
      CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median
      RFS (95% confidence interval; 95% CI) 21.4 (7.8-35.1) vs. 8.7 (6.8-10.5) months,
      P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2-34.2) months, P
      < 0.001] than those with low Immunoscores (<= 2). After stratification by CRS,
      the Immunoscore retained a statistically significant prognostic value for OS. The
      areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS
      were 0.711 [95% CI 0.642-0.781] and 0.675[95% CI 0.601-0.749] (P = 0.492),
      whereas the AUROC of the Immunoscore system for OS was larger than that of the
      CRS system [0.759 (95% CI 0.699-0.818) vs. 0.660 (95% CI 0.592-0.727); P =
      0.029]. CONCLUSIONS: The Immunoscore of liver metastases can be applied to
      predict the prognosis of CRCLM patients following liver resection.

PMID- 29204703
TI  - An intra-articular synovial lipoma of the hip, possibly causing osteoarthritis: a
      case report and review of the literature.
AB  - In this report, we present the case of an intra-articular synovial lipoma in a 58
      year-old female with a coincident marked unilateral hip osteoarthritis. This
      patient suffered from right hip pain that developed gradually over 2 years.
      Physical examination noted decreased range of motion and evidence of impingement.
      MR and CT images showed an intra-articular fat-intense mass in the hip joint that
      was excised and confirmed as a synovial lipoma on histology. This case reveals
      that an intra-articular lipoma of the hip could be accompanied by pain or
      impingement and followed by hip osteoarthritis even in the absence of trauma.

PMID- 29204704
TI  - Re: A prospective, randomized trial comparing thulium vapoenucleation with
      holmium laser enucleation of the prostate for the treatment of symptomatic benign
      prostatic obstruction: perioperative safety and efficacy.

PMID- 29204705
TI  - RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary
      and metastatic prostate cancer disease.
AB  - BACKGROUND: The cytokine system RANKL (receptor activator of NF-kappaB ligand),
      its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role
      in bone turnover. Our investigation was conducted to describe the gene expression
      at primary tumour site in prostate cancer patients and correlate the results with
      Gleason Score and PSA level. METHODS: Seventy-one samples were obtained from
      prostate cancer patients at the time of radical prostatectomy and palliative
      prostate resection (n = 71). Patients with benign prostate hyperplasia served as
      controls (n = 60). We performed real-time RT-PCR after microdissection of the
      samples. RESULTS: The mRNA expression of RANK was highest in tumour tissue from
      patients with bone metastases (p < 0.001) as compared to BPH or locally confined
      tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or
      >= 7, p = 0.028) or PSA level (< 10 or >= 10 ug/l, p = 0.004). RANKL and OPG mRNA
      expression was higher in tumour tissue from patients with metastatic compared to
      local disease. The RANKL/OPG ratio was low in normal prostate tissue and high
      tumours with bone metastases (p < 0.05). Expression of all three cytokines was
      high in BPH tissue but did not exceed as much as in the tumour tissue.
      CONCLUSION: We demonstrated that RANK, RANKL and OPG are directly expressed by
      prostate cancer cells at the primary tumour site and showed a clear correlation
      with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression
      is also detectable, but RANK expression does not exceed as much as compared to
      tumour tissue.

PMID- 29204706
TI  - MiR-199a suppresses prostate cancer paclitaxel resistance by targeting YES1.
AB  - PURPOSE: Prostate cancer chemoresistance is a major contributor to the poor
      survival of patients. MicroRNAs (miRNAs) play an important role in regulating
      cancer resistance. Here we aim to explore the role and mechanism of miR-199a in
      regulating prostate cancer resistance. METHODS: MiR-199a expressions in human
      prostate cancer tissues and cell lines were investigated with real-time PCR (RT
      PCR). MiR-199a was ectopically overexpressed in PC3 cells, and resistance to
      paclitaxel (PTX) was evaluated consequently. The interaction between miR-199a and
      the oncogene Yamaguchi sarcoma viral homolog 1 (YES1) was assessed after miR-199a
      overexpression. YES1 was ectopically overexpressed, followed by evaluation of PTX
      resistance. The efficacy of miR-199a as a therapeutic agent was also investigated
      in vivo. RESULTS: Downregulation of miR-199a was characteristic of prostate
      cancer, particularly recurrent cancers. MiR-199a was suppressed in PTX-resistant
      cell line. Overexpression of miR-199a inhibited PTX resistance. YES1 was a target
      of miR-199a, and overexpression of YES1 reversed the effect of miR-199a in
      suppressing PTX resistance. In vivo, miR-199a increased tumor PTX sensitivity.
      CONCLUSIONS: The downregulation of miR-199a contributes to PTX resistance in
      prostate cancer. YES1 mediates the regulation of miR-199a in prostate cancer PTX
      resistance. This miR-199a replacement therapy has potential to overcome PTX
      resistance.

PMID- 29204707
TI  - Ocular surface and tear film status among contact lens wearers and non-wearers
      who use VDT at work: comparing three different lens types.
AB  - PURPOSE: To analyze differences in the ocular surface appearance and tear film
      status of contact lens wearers and non-wearers in a group of visual display
      terminals (VDT) workers and additionally to assess differences between lens
      materials. METHODS: Cross-sectional study of 236 office workers, of whom 92 were
      contact lens wearers. Workers provided information on their contact lenses
      (conventional hydrogel, silicone hydrogel or rigid gas permeable lenses) and
      exposure to VDT at work. Ocular surface and tear film status were determined by
      the presence of bulbar, limbal and lid redness, lid roughness and corneal
      staining type, and by Schirmer's and tear break-up time tests (TBUT). A
      generalized linear model was used to calculate the crude (cRR) and age- and sex
      adjusted (aRR) relative risk to measure the association between ocular surface
      and tear film abnormalities and contact lens use and type. RESULTS: The aRR of
      ocular surface abnormalities was higher in contact lens wearers compared to non
      wearers: bulbar redness (aRR 1.69; 95% CI 1.25-2.30), limbal redness (aRR 2.87;
      1.88-4.37), lid redness (aRR 2.53; 1.35-4.73) and lid roughness (aRR 7.03; 1.31
      37.82). VDT exposure > 4 h/day increased wearers' risk of limbal and lid redness.
      Conventional hydrogel wearers had the highest risk of ocular surface
      abnormalities, followed by silicone hydrogel wearers. Both contact and non
      contact lens wearers had a high prevalence of altered TBUT (77.3 and 75.7%
      respectively) and Schirmer (51.8 and 41.3%). CONCLUSIONS: Regular contact lens
      use during VDT exposure at work increases risk of bulbar, limbal and lid redness,
      and lid roughness, especially in soft contact lens wearers. The high prevalence
      of altered TBUT and Schirmer's results in all participants suggests that VDT use
      greatly affects tear film characteristics.

PMID- 29204708
TI  - A systematic literature review of the prevalence of and risk factors for
      supportive care needs among women with gynaecological cancer and their
      caregivers.
AB  - PURPOSE: This review aimed to determine the prevalence of met and unmet needs,
      and the risk factors for unmet needs among people affected by gynaecological
      cancer. METHODS: The review was undertaken using the PRISMA guidelines. Eligible
      studies were identified though a range of electronic databases in October and
      November 2016. Study quality was independently appraised by two people. RESULTS:
      Thirty-seven studies were included (1 review, 24 quantitative and 12
      qualitative). The evidence was of mixed quality. The total burden of needs
      affecting women with gynaecological cancer and also their caregivers
      predominately related to comprehensive care and psychological concerns. The major
      moderate-to-high-level unmet needs of women with gynaecological cancer were for
      help explicitly with fear of recurrence, worries of caregivers and fatigue, and
      for women who developed lymphoedema were with pain and associated costs.
      Qualitative studies identified disease-specific needs related to sexuality issues
      (including fertility, sexual functioning, relationship concerns, managing vaginal
      changes, pregnancy care, premature menopause), genetic testing and disease
      specific peer support. Women at risk of having unmet needs include those who are
      younger, with advanced disease, with lymphoedema or a high symptom burden, are
      unable to work, have mental health issues, have poor social support or live in
      rural or remote locations. CONCLUSIONS: Understanding the needs of women with
      gynaecological cancer and their caregivers is essential to improving care and
      outcomes. Current data are limited thus there is a need for qualitative studies
      of patient-caregiver dyad and vulnerable subgroups and well-designed quantitative
      studies of women with each type of gynaecological and their caregivers.

PMID- 29204709
TI  - Modality of exercise influences rate of decrease in depression for cancer
      survivors with elevated depressive symptomatology.
AB  - PURPOSE: This three-arm feasibility controlled trial examined whether different
      exercise modalities provide reductions in depression symptoms to cancer survivors
      with elevated depression. METHODS: Thirty-two participants (58.9 +/- 9.4 years)
      were allocated to a 12-week supervised exercise group (EX; n = 10), a self
      managed home-based exercise group (SMHB; n = 8), or a usual care control group
      (CONT; n = 14). EX performed two supervised resistance and aerobic sessions per
      week. SMHB were provided with printed material about benefits of exercise and
      encouraged to complete 150 min of exercise weekly. CONT received no exercise or
      printed material and were encouraged to maintain usual activity. RESULTS: A group
      * time interaction was found for the primary outcome of depression scores,
      measured using the Hospital Anxiety and Depression Scale (HADS-D; p = .008). SMHB
      (6.4 +/- 5.3 to 2.2 +/- 2.9, p = .006) and EX (6.9 +/- 4.2 to 4.0 +/- 2.4, p =
      .021) interventions both effectively reduced HADS-D scores compared to CONT (7.2
      +/- 2.5 to 7.7 +/- 3.6). SMHB decreased depression to a greater extent, and this
      occurred more rapidly with greatest changes noted at 6 weeks (d = 0.50). Further
      favourable outcomes for exercise were also noted for several secondary outcome
      measures. CONCLUSION: The rate of exercise-related reduction in depression is
      influenced by the modality of exercise. However, increasing the duration of the
      programme appears to diminish the favourable short-term response to self-managed
      exercise with subsequent secondary outcomes of mental health favouring supervised
      exercise.

PMID- 29204711
TI  - Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are
      Alcohol Targets in Neurons.
AB  - Among all members of the voltage-gated, TM6 ion channel superfamily, the proteins
      that constitute calcium- and voltage-gated potassium channels of large
      conductance (BK) and their coding genes are unique for their involvement in
      ethanol-induced disruption of normal physiology and behavior. Moreover, in vitro
      studies document that BK activity is modified by ethanol with an EC50~23 mM,
      which is near blood alcohol levels considered legal intoxication in most states
      of the USA (0.08 g/dL = 17.4 mM). Following a succinct introduction to our
      current understanding of BK structure and function in central neurons, with a
      focus on neural circuits that contribute to the neurobiology of alcohol use
      disorders (AUD), we review the modifications in organ physiology by alcohol
      exposure via BK and the different molecular elements that determine the ethanol
      response of BK in alcohol-naive systems, including the role of an ethanol
      recognizing site in the BK-forming slo1 protein, modulation of accessory BK
      subunits, and their coding genes. The participation of these and additional
      elements in determining the response of a system or an organism to protracted
      ethanol exposure is consequently analyzed, with insights obtained from
      invertebrate and vertebrate models. Particular emphasis is put on the role of BK
      and coding genes in different forms of tolerance to alcohol exposure. We finally
      discuss genetic results on BK obtained in invertebrate organisms and rodents in
      light of possible extrapolation to human AUD.

PMID- 29204710
TI  - Chemotherapy-related neuropathic symptom management: a randomized trial of an
      automated symptom-monitoring system paired with nurse practitioner follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate a new care model to reduce
      chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was
      prospectively compared to an automated symptom-monitoring and coaching system,
      SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by
      moderate to severe symptoms. METHODS: Patients beginning chemotherapy were
      randomized to usual care (UC) or to the SCH intervention. This sub-analysis
      included only taxane/platin therapies. Participants called the automated
      telephone symptom-monitoring system daily to report numbness and tingling. The
      monitoring system recorded patient-reported neuropathic symptom severity,
      distress, and activity interference on a 0-10 scale. UC participants were
      instructed to call their oncologist for symptom management. SCH participants with
      symptom severity of >= 4 received automated self-care strategies, and a nurse
      practitioner (NP) provided guideline-based care. RESULTS: There were 252
      participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up
      was 90.2 +/- 39.9 days (81.1 +/- 40.3 calls). SCH participants had fewer days of
      moderate (1.8 +/- 4.0 vs. 8.6 +/- 17.3, p < 0.001) and severe chemotherapy
      induced peripheral neuropathy symptoms (0.3 +/- 1.0 vs. 1.1 +/- 5.2, p = 0.006).
      SCH participants had fewer days with moderate and severe symptom-related distress
      (1.4 +/- 3.7 vs. 6.9 +/- 15.0, p < 0.001; 0.2 +/- 0.9 vs. 1.5 +/- 6.1, p = 0.001)
      and trended towards less activity interference (3.3 +/- 1.9 vs. 3.8 +/- 2.1, p =
      0.08). Other neuropathic symptoms were addressed in 5.8-15.4% of SCH follow-up
      calls. CONCLUSIONS: The SCH system effectively identified neuropathic symptoms
      and their severity and, paired with NP follow-up, reduced symptom prevalence,
      severity, and distress compared to usual care.

PMID- 29204712
TI  - Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking.
AB  - Ethanol produces intoxication through actions on numerous molecular and cellular
      targets. Adaptations involving these and other targets contribute to chronic drug
      actions that underlie continued and problematic drinking. Among the mechanisms
      involved in these ethanol actions are alterations in presynaptic mechanisms of
      synaptic transmission, including presynaptic protein function and excitation
      secretion coupling. At synapses in the central nervous system (CNS), excitation
      secretion coupling involves ion channel activation followed by vesicle fusion and
      neurotransmitter release. These mechanisms are altered by presynaptic
      neurotransmitter receptors and prominently by G protein-coupled receptors
      (GPCRs). Studies over the last 20-25 years have revealed that acute ethanol
      exposure alters neurotransmitter secretion, with especially robust effects on
      synapses that use the neurotransmitter gamma-aminobutyric acid (GABA).
      Intracellular signaling pathways involving second messengers such as cyclic AMP
      and calcium are implicated in these acute ethanol actions. Ethanol-induced
      release of neuropeptides and small molecule neurotransmitters that act on
      presynaptic GPCRs also contribute to presynaptic potentiation at synapses in the
      amygdala and hippocampus and inhibition of GABA release in the striatum.
      Prolonged exposure to ethanol alters neurotransmitter release at many CNS
      GABAergic and glutamatergic synapses, and changes in GPCR function are implicated
      in many of these neuroadaptations. These presynaptic neuroadaptations appear to
      involve compensation for acute drug effects at some synapses, but "allostatic"
      effects that result in long-term resetting of synaptic efficacy occur at others.
      Current investigations are determining how presynaptic neuroadaptations
      contribute to behavioral changes at different stages of alcohol drinking, with
      increasing focus on circuit adaptations underlying these behaviors. This chapter
      will discuss the acute and chronic presynaptic effects of ethanol in the CNS, as
      well as some of the consequences of these effects in amygdala and corticostriatal
      circuits that are related to excessive seeking/drinking and ethanol abuse.

PMID- 29204713
TI  - GABAA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol:
      Genetic and Pharmacological Evidence.
AB  - Ethanol's reinforcing and subjective effects, as well as its ability to induce
      relapse, are powerful factors contributing to its widespread use and abuse. A
      significant mediator of these behavioral effects is the GABAA receptor system.
      GABAA receptors are the target for gamma-aminobutyric acid (GABA), the major
      inhibitory neurotransmitter in the CNS. Structurally, they are pentameric,
      transmembrane chloride ion channels comprised of subunits from at least eight
      different families of distinct proteins. The contribution of different GABAA
      subunits to ethanol's diverse abuse-related effects is not clear and remains an
      area of research focus. This chapter details the clinical and preclinical
      findings supporting roles for different alpha, beta, gamma, and delta subunit
      containing GABAA receptors in ethanol's reinforcing, subjective/discriminative
      stimulus, and relapse-inducing effects. The reinforcing properties of ethanol
      have been studied the most systematically, and convergent preclinical evidence
      suggests a key role for the alpha5 subunit in those effects. Regarding ethanol's
      subjective/discriminative stimulus effects, clinical and genetic findings support
      a primary role for the alpha2 subunit, whereas preclinical evidence implicates
      the alpha5 subunit. At present, too few studies investigating ethanol relapse
      exist to make any solid conclusions regarding the role of specific GABAA subunits
      in this abuse-related effect.

PMID- 29204714
TI  - Comprehensive profiling of functional attributes, virulence potential and
      evolutionary dynamics in mycobacterial secretomes.
AB  - Mycobacterium is an interesting genus which not only includes intimidating
      pathogens, associated with severe devastations globally, but also comprises of
      non-pathogenic eco-friendly members that detoxify environmental pollutants.
      Secretory proteins of the mycobacterial communities are essential components
      which are firmly believed to facilitate proper cross-talk and apt communication
      with host cellular surroundings and environmental niche. Secretory elements also
      play vital roles in mycobacterial pathogenesis. In the present endeavor, an
      extensive profiling of mycobacterial secretomes, considering both pathogenic and
      non-pathogenic members, has been executed. Thorough analysis on amino acid
      composition and functional behavior of the mycobacterial secretory proteins has
      also been performed. In-depth scrutiny of biosynthetic cost of the secretory
      proteins with respect to the non-secretory ones indicated that the genus
      Mycobacterium strictly follows the policy of cost-minimization among the sets of
      imperative secretory proteins. Comprehensive assessment of potential virulence
      among the key secretory components signified that the pathogenic mycobacterial
      members possess a larger share of potentially virulent secretory elements in
      comparison to their non-pathogenic counterparts. Present analysis also revealed
      contrasted evolutionary features of the secretomes wherein secretory proteins
      were found to evolve faster than non-secretory proteins in mycobacterial
      pathogens but not in the concerned non-pathogens. Outcomes of present
      investigation promise to provide novel insights into the enigma of mycobacterial
      pathogenesis, bioremediation and adaptation in diverse niche and aid further
      scientific investigations associated with concerned research area.

PMID- 29204715
TI  - Insight into the reaction mechanism of lipoyl synthase: a QM/MM study.
AB  - Lipoyl synthase (LipA) catalyses the final step of the biosynthesis of the lipoyl
      cofactor by insertion of two sulfur atoms at the C6 and C8 atoms of the protein
      bound octanoyl substrate. In this reaction, two [4Fe4S] clusters and two
      molecules of S-adenosyl-L-methionine are used. One of the two FeS clusters is
      responsible for the generation of a powerful oxidant, the 5'-deoxyadenosyl
      radical (5'-dA*). The other (the auxiliary cluster) is the source of both sulfur
      atoms that are inserted into the substrate. In this paper, the spin state of the
      FeS clusters and the reaction mechanism is investigated by the combined quantum
      mechanical and molecular mechanics approach. The calculations show that the
      ground state of the two FeS clusters, both in the [4Fe4S]2+ oxidation state, is a
      singlet state with antiferromagnetically coupled high-spin Fe ions and that there
      is quite a large variation of the energies of the various broken-symmetry states,
      up to 40 kJ/mol. For the two S-insertion reactions, the highest energy barrier is
      found for the hydrogen-atom abstraction from the octanoyl substrate by 5'-dA*.
      The formation of 5'-dA* is very facile for LipA, with an energy barrier of 6
      kJ/mol for the first S-insertion reaction and without any barrier for the second
      S-insertion reaction. In addition, the first S ion attack on the C6 radical of
      octanoyl was found to take place directly by the transfer of the H6 from the
      substrate to 5'-dA*, whereas for the second S-insertion reaction, a C8 radical
      intermediate was formed with a rate-limiting barrier of 71 kJ/mol.

PMID- 29204717
TI  - Correction to: Molecular characterization of Blastocystis sp. in captive wild
      animals in Qinling Mountains.
AB  - There were errors in Fig. 1 of the originally published article. Correct fig. 1
      is presented here.

PMID- 29204719
TI  - Correction to: Electrocardiogram-based predictors for arrhythmia after spinal
      cord injury.
AB  - There is a typographical error in the formula presented for QTVI. While the
      formula was correctly applied to the data presented, the description of the
      formula has an incorrectly placed parenthesis. It should read.

PMID- 29204718
TI  - Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection
      of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and
      paraganglioma in the pediatric population.
AB  - PURPOSE: To evaluate and compare diagnostic performance of 68Ga-DOTA(0)-Tyr(3)
      octreotate (68Ga-DOTATATE) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron
      emission tomography-computed tomography (PET/CT) and anatomic imaging using
      computed tomography and/or magnetic resonance (CT/MR) imaging in detection of
      SDHx-related pheochromocytomas and paragangliomas (PPGLs) in pediatric patients.
      METHODS: Nine pediatric patients (5:4, girls:boys; 14.6 +/- 2.0 years) with an
      SDHx-related mutation (SDHB:SDHA:SDHD, n = 7:1:1) were included in this
      retrospective study. At the time of initial diagnosis, 7/9 patients had
      metastatic disease. They underwent CT/MR imaging along with PET/CT using 68Ga
      DOTATATE (n = 9), 18F-FDG (n = 8), and positron emission tomography-magnetic
      resonance imaging (PET/MR) using 18F-FDG (n = 1). In this manuscript, 18F-FDG
      PET/CT refers to both 18F-FDG PET/CT and 18F-FDG PET/MR. The per-lesion, per
      region, and per-patient detection rates were compared and calculated for each of
      the imaging modalities. A composite of all functional and anatomic imaging
      studies served as the imaging comparator. RESULTS: Eight out of nine patients
      were positive for PPGLs on the imaging studies that demonstrated 107 lesions in
      22 anatomic regions on the imaging comparator. The per-lesion detection rates for
      68Ga-DOTATATE PET/CT, 18F-FDG PET/CT, and CT/MR imaging were 93.5% (95%CI, 87.0%
      to 97.3%); 79.4% (95%CI, 70.5% to 86.6%); and 73.8% (95%CI, 64.5% to 81.9%),
      respectively. The per-lesion detection rate for 68Ga-DOTATATE PET/CT was
      significantly higher than that of 18F-FDG PET/CT (p = 0.001) or CT/MR imaging (p
      < 0.001). In all of the anatomic regions except abdomen, the per-lesion detection
      rates for 68Ga-DOTATATE PET/CT was found to be equal or superior to 18F-FDG
      PET/CT, and CT/MR imaging. The per-region detection rate was 100% (95%CI, 84.6%
      to 100%) for 68Ga-DOTATATE PET/CT and 90.9% (95%CI, 70.8% to 98.9%) for both 18F
      FDG PET/CT and CT/MR imaging. The per-patient detection rates for 68Ga-DOTATATE
      PET/CT, 18FDG PET/CT, and CT/MR imaging were all 100% (95%CI, 63.1% to 100%).
      CONCLUSION: Our preliminary study demonstrates the superiority of 68Ga-DOTATATE
      PET/CT in localization of SDHx-related PPGLs in pediatric population compared to
      18F-FDG PET/CT and CT/MR imaging with the exception of abdominal (excluding
      adrenal and liver) lesions, and suggests that it might be considered as a first
      line imaging modality in pediatric patients with SDHx-related PPGLs.

PMID- 29204721
TI  - Molecular docking studies of bioactive compounds from Annona muricata Linn as
      potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins.
AB  - Annona muricata Linn or usually identified as soursop is a potential anticancer
      plant that has been widely reported to contain valuable chemopreventive agents
      known as annonaceous acetogenins. The antiproliferative and anticancer activities
      of this tropical and subtropical plant have been demonstrated in cell culture and
      animal studies. A. muricata L. exerts inhibition against numerous types of cancer
      cells, involving multiple mechanism of actions such as apoptosis, a programmed
      cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless,
      the binding mode and the molecular interactions of the plant's bioactive
      constituents have not yet been unveiled for most of these mechanisms. In the
      current study, we aim to elucidate the binding interaction of ten bioactive
      phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins
      viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis
      software, Autodock 4.2. The stability of the complex with highest affinity was
      evaluated using MD simulation. We compared the docking analysis of these
      substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study
      identified the potential chemopreventive agent among the bioactive compounds. We
      also characterized the important interacting residues of protein targets which
      involve in the binding interaction. Results displayed that anonaine, a
      benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus
      indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic
      family of proteins.

PMID- 29204720
TI  - Effect of mercury on pollen germination and tube growth in Lilium longiflorum.
AB  - Pollen development and germination were adversely affected by the presence of
      mercury, whereas low-concentrations stimulated the whole procedure. Mercury
      caused morphological anomalies during the tube growth, characterized by
      irregularly increasing diameters and swelling tips. The main effect was the
      anomalous cell wall formation at the tip where a substantial number of organelles
      were found reducing the secretory vesicles. The dense organelle concentration
      caused a significant reduction of cytoplasmic movement integrity, and the cytosol
      streaming was gradually reduced or stopped completely. Electron dense,
      multilamellar myelin-like structures (MMS) of membranous material were frequently
      present, in close contact with plasmalemma or away from it. A loose network of
      fibrillar material and spherical aggregates mostly at the tip region were
      observed which progressively were loosened into the surrounding medium. Elevated
      mercury concentrations can affect plant reproduction, resulting in anomalies in
      gamete development and consequently loss of plant biodiversity.

PMID- 29204722
TI  - Preparation of NGF encapsulated chitosan nanoparticles and its evaluation on
      neuronal differentiation potentiality of canine mesenchymal stem cells.
AB  - Sustained and controlled release of neurotrophic factors in target tissue through
      nanomaterial based delivery system could be a better strategy for nerve tissue
      regeneration. The present study aims to prepare the nerve growth factor (NGF)
      encapsulated chitosan nanoparticles (NGF-CNPs) and its evaluation on neuronal
      differentiation potentiality of canine bone marrow derived mesenchymal stem cells
      (cBM-MSCs). The NGF-CNPs were prepared by ionotropic gelation method with
      tripolyphosphate (TPP) as an ionic cross-linking agent. Observations on
      physiochemical properties displayed the size of nanoparticles as 80-90 nm with
      positive zeta potential as well as an ionic interaction between NGF and
      nanoparticle. NGF loading efficiency was found to be 61% while its sustained
      release was observed by an in vitro release kinetics study. These nanoparticles
      were found to be cytocompatible to cBM-MSCs when supplemented at a concentration
      upto 4 mg/ml in culture media. The NGF-CNP supplemented culture media was able to
      transdifferentiate the preinduced cBM-MSCs into neurons in a better way than
      unbound NGF supplementation. Further, it was also noticed that NGF-CNPs were able
      to transdifferentiate cBM-MSCs without any chemical based preinduction. In
      conclusion, our findings propose that NGF-CNPs are capable of releasing bioactive
      NGF with the ability to transdifferentiate mesenchymal stem cells into neurons,
      suggesting its potential future application in nerve tissue regeneration.

PMID- 29204723
TI  - Theoretical predictions of anti-corrosive properties of THAM and its derivatives.
AB  - We present quantum chemical theoretical estimations of the anti-corrosive
      properties of THAM (tris(hydroxymethyl)aminomethane) and three derivatives that
      differ in the number of benzene rings: THAM-1 (2-amino-3-hydroxy-2
      (hydroxymethyl) propylobenzoate), THAM-2 (2-amino-2-(hydroxymetyl)prapan-1,3
      diyldibenzoate) and THAM-3 (2-amino-propan-1,2,3-triyltribenzoate). Fourteen
      exchange-correlation functionals based on the density functional theory (DFT)
      were chosen for quantum chemical study of THAM derivatives. The objective was to
      examine the effect of benzene rings on potential anti-corrosive properties of
      THAM compounds. The results indicate that the addition of benzene rings in THAM
      derivatives is likely to significantly enhance electrostatic bonding of a THAM
      based coating to a presented metal surface and, thus, its adhesion and long-term
      effect in corrosion inhibition. Whereas it is clear that all three derivatives
      appear to be superior in their bonding characteristics to pure THAM, the
      potential order of merit between the three is less clear, although THAM-3
      presents as possibly superior.

PMID- 29204725
TI  - "Sex Will Make Your Fingers Grow Thin and Then You Die": The Interplay of
      Culture, Myths, and Taboos on African Immigrant Mothers' Perceptions of
      Reproductive Health Education with Their Daughters Aged 10-14 Years.
AB  - This paper examines the convergence of culture, myths, and taboos surrounding
      reproductive health issues African immigrant women, living in the United States,
      learned during childhood in their countries of origin. We also discuss how
      mothers' perceptions of reproductive health education (RHE) influenced the
      education of their own daughters aged 10-14 years. This was a qualitative
      descriptive study. Data were collected via interviews and demographic survey. The
      sample size was 20 African immigrant mothers living in a mid-sized city in the
      U.S. Interviews were transcribed verbatim. Qualitative data was analyzed using
      qualitative content analysis. Myths and taboos related to menstruation, sexual
      intercourse, pregnancy, and HIV/AIDS were reported by the women interviewed.
      Discussion of these issues was largely taboo, and most myths the mothers learned
      growing up pertained to sexual intercourse, pregnancy prevention, and pregnancy
      termination using non-hormonal ingested substances. Myths and taboos about sexual
      issues are widespread in Africa and are propagated to control sexual behavior,
      especially that of unmarried people, particularly women. By examining these myths
      and taboos, we are able to somewhat contextualize the mothers' immigrant
      experience regarding RHE. Although myths were reported, the majority of mothers
      did not appear to believe them. The most significant taboo reported was sexual
      intercourse. This in turn led to mothers' overemphasis on abstinence for their
      daughters. It is also noteworthy that this sample contained mainly African women
      who overall were highly educated, spoke English, and could adequately navigate
      life in the U.S. It is unclear what the results would be if we were to examine
      African immigrant women with less achievements in these areas.

PMID- 29204726
TI  - Psychopathology and Associated Risk Factors Among Forcibly Displaced Syrian
      Children and Adolescents.
AB  - More than half of the 2.7 million registered Syrian refugees in Turkey are under
      18 years of age. This study investigates prevalence of psychopathology and
      associated risk factors in refugee children in Turkey. Of a total of 218 children
      aged 9-15 years, 56.2% lost someone important to them, 55.1% saw dead or wounded
      people, 70.4% witnessed explosions or gun battles, 42.5% witnessed people being
      tortured and 25.6% personally experienced cruelty/torture during war. Prevalence
      of PTSD was 18.3% and that of anxiety-related disorders were as high as 69.0%.
      Death of an important person (p = .032) and male gender (p = .040) were
      associated with PTSD; whilst exposure to cruelty or torture (p = .014) and
      increasing duration of refuge (p = .042) were significantly associated with
      development of anxiety disorders. Findings of the present study reveals existence
      of the expected but unspoken mental health needs among the Syrian children in
      Turkey.

PMID- 29204727
TI  - Economic evaluation of 2014 cholera outbreak in Ghana: a household cost analysis.
AB  - INTRODUCTION: Ghana experienced its worst cholera outbreak in three decades in
      2014. Evidence of cholera economic costs on affected households has been limited.
      This study aimed at determining economic costs on households affected by the 
      cholera outbreak in a Coastal Region of Ghana. METHODS: Two districts; High and
      Low Incidence Areas (HIA and LIA) were selected in comparative cost analysis and
      disease impact on affected households assessed based on scientifically documented
      economic indicators. A total of 418 (282 HIA and 136 LIA) households that
      experienced at least one case of cholera infection were interviewed. Direct and
      indirect costs were estimated. Correlates of household's cholera infection were
      estimated using Tobit Regression model in STATA 13. RESULTS: Average direct cost
      to households in HIA amounted to USD 106.88, almost 2 folds higher than LIA (USD
      62.02). Potential cost saving of an episode of cholera is USD 99,201.28 in LIA
      and raises almost 8 folds in HIA (USD 782,611.60). Households in lowest income
      category had the highest incidence of cholera (0.073) compared to other
      categories plus other factors were significant in explaining cholera incidence.
      CONCLUSIONS: The study showed considerable differences in HIA and LIA costs with
      higher household economic impact of cholera on the lowest income category.
      Results underscore the need for pragmatic policy interventions  to avert
      recurrent outbreaks and emphasis huge potential  cost saving with reducing 
      cholera cases.

PMID- 29204724
TI  - Reversal of Hartmann's procedure: still a complicated operation.
AB  - Hartmann's procedure, colonic resection with an end colostomy and rectal closure,
      is used in a variety of surgical emergencies. It is a common surgical procedure
      that is often practiced in patients with colonic obstruction and colonic
      perforation, resolving the acute clinical situation in the majority of cases.
      Reversal of Hartmann's procedure with restoration of bowel continuity occurs in a
      significantly low percentage of patients. There are several reasons contributing
      to the fact that many patients remain with a permanent colostomy following
      Hartmann's procedure. These include factors related to the patients' clinical
      status but also to the significant difficulty and morbidity related to the
      surgical reversal of Hartmann's procedure. The aim of this study was to review
      the factors related to the fairly low percentage of patients undergoing
      Hartmann's reversal as well as surgical techniques that could help surgeons
      restore intestinal continuity following Hartmann's procedure and deal with the
      postoperative outcomes.

PMID- 29204728
TI  - Variation in outpatient emergency department utilization in Texas Medicaid: a
      state-level framework for finding "superutilizers".
AB  - BACKGROUND: Very frequent outpatient emergency department (ED) use-so called
      "superutilization"-at the state level is not well-studied. To address this gap,
      we examined frequent ED utilization in the largest state Medicaid population to
      date. METHODS: Using Texas Medicaid (the third largest in the USA) claims data,
      we examined the variability in expenditures, sociodemographics, comorbidities,
      and persistence across seven levels of ED utilization/year (i.e., 1, 2, 3-4, 5-6,
      7-9, 10-14, and >= 15 visits). We classified visits into emergent and non
      emergent categories using the most recent New York University algorithm. RESULTS:
      Thirty-one percent (n = 346,651) of Texas Medicaid adult enrollees visited the ED
      at least once in 2014. Enrollees with >= 3 ED visits accounted for 8.5% of all
      adult patients, 60.4% of the total ED visits, and 62.1% of the total ED
      expenditures. Extremely frequent ED users (>= 10 ED visits) represented < 1% of
      all users but accounted for 15.5% of all ED visits and 17.4% of the total ED
      costs. The proportions of ED visits classified as non-emergent or emergent, but
      primary care treatable varied little as ED visits increased. Overall,
      approximately 13% of ED visits were considered not preventable or avoidable.
      CONCLUSIONS: The Texas Medicaid population has a substantial burden of chronic
      disease with only modest increases in substance use and mental health diagnoses
      as annual visits increase. Understanding the characteristics that lead to
      frequent ED use is vital to developing strategies and Medicaid policy to reduce
      high utilization.

PMID- 29204730
TI  - Development and Validation of a Japanese Fidelity Scale for Supported Employment.
AB  - The Individual Placement and Support (IPS) model of supported employment is an
      evidence based practice. Although several agencies have been trying to implement
      the IPS-model since 2005 in Japan, there was no tool to assess the quality. This
      study developed a Japanese version of the 25-item Individualized Supported
      Employment Fidelity Scale (J-ISEF), a new Japanese fidelity tool for supported
      employment based on the IPS model. A working group consisting of researchers and
      practitioners was formed to develop J-ISEF based on IPS-25. Some experts of the
      group visited the community agencies in Vermont before the development process.
      Twenty-six eligible agencies were identified using snowball sampling, and 14
      agencies of them agreed and participated at T1. We conducted three cross
      sectional surveys (T1, T2 and T3), using the new scale. The first evaluation
      period (T1) was between September 2013 and February 2014, the second (T2) between
      September 2014 and February 2015, and the third (T3) between October 2015 and
      February 2016. High inter-rater reliability (ICC = 0.98 for the entire scale) was
      confirmed from T1 data. The total score and the service subscale total were
      positively correlated with employment rate (P < 0.05). A new fidelity scale, J
      ISEF, is developed as a quality assessment tool for evidence-based supported
      employment programs in Japan. The evidence for its inter-rater reliability and
      criterion-related validity is promising.

PMID- 29204729
TI  - "Nutrient-sensing" and self-renewal: O-GlcNAc in a new role.
AB  - Whether embryonic, hematopoietic or cancer stem cells, this metabolic
      reprogramming is dependent on the nutrient-status and bioenergetic pathways that
      is influenced by the micro-environmental niches like hypoxia. Thus, the
      microenvironment plays a vital role in determining the stem cell fate by inducing
      metabolic reprogramming. Under the influence of the microenvironment, like
      hypoxia, the stem cells have increased glucose and glutamine uptake which result
      in activation of hexosamine biosynthesis pathway (HBP) and increased O-GlcNAc
      Transferase (OGT). The current review is focused on understanding how HBP, a
      nutrient-sensing pathway (that leads to increased OGT activity) is instrumental
      in regulating self-renewal not only in embryonic and hematopoietic stem cells
      (ESC/HSC) but also in cancer stem cells.

PMID- 29204731
TI  - Improved biosynthesis of silver nanoparticles using keratinase from
      Stenotrophomonas maltophilia R13: reaction optimization, structural
      characterization, and biomedical activity.
AB  - In the present study, keratinase from Stenotrophomonas maltophilia R13 was used
      for the first time as a reducing agent for the eco-friendly synthesis of AgNPs.
      The keratinase produced by strain R13 was responsible for the reduction of silver
      ions and the subsequent formation of AgNPs. Maximum AgNP synthesis was achieved
      using 2 mM AgNO3 at pH 9 and 40  degrees C. Electron microscopy and dynamic light
      scattering analysis showed AgNPs were spherical and of average diameter ~ 8.4 nm.
      X-ray diffraction revealed that AgNPs were crystalline. FTIR indicated AgNPs were
      stabilized by proteins present in the crude enzyme solution of strain R13. AgNPs
      exhibited a broad antimicrobial spectrum against several pathogenic
      microorganisms, and the antimicrobial mechanism appeared to involve structural
      deformation of cells resulting in membrane leakage and subsequent lysis. AgNPs
      also displayed 1,1-diphenyl-2-picrylhydrazyl (IC50 = 0.0112 mg/ml), 2,2'-azinobis
      3-ethylbenzothiazoline-6-sulfonate radical scavenging (IC50 = 0.0243 mg/ml), and
      anti-collagenase (IC50 = 23.5 mg/ml) activities.

PMID- 29204732
TI  - Peripheral Leptin Signaling Mediates Formalin-Induced Nociception.
AB  - Accumulating evidence suggests that obesity is associated with chronic pain.
      However, whether obesity is associated with acute inflammatory pain is unknown.
      Using a well-established obese mouse model induced by a high-fat diet, we found
      that: (1) the acute thermal pain sensory threshold did not change in obese mice;
      (2) the model obese mice had fewer nociceptive responses in formalin-induced
      inflammatory pain tests; restoring the obese mice to a chow diet for three weeks
      partly recovered their pain sensation; (3) leptin injection induced significant
      phosphorylation of STAT3 in control mice but not in obese mice, indicating the
      dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4)
      leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin
      leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2
      inhibitor AG 490 in wild-type mice reduced their nociceptive responses in
      formalin tests. These results indicate that leptin plays a role in nociception
      induced by acute inflammation and that interference in the leptin-leptin receptor
      pathway could be a peripheral target against acute inflammatory pain.

PMID- 29204733
TI  - Comparative nutritional and mycochemical contents, biological activities and
      LC/MS screening of tuber from new recipe cultivation technique with wild type
      tuber of tiger's milk mushroom of species Lignosus rhinocerus.
AB  - Tiger's milk mushroom is known for its valuable medicinal properties, especially
      the tuber part. However, wild tuber is very hard to obtain as it grows
      underground. This study first aimed to cultivate tiger's milk mushroom tuber
      through a cultivation technique, and second to compare nutritional and
      mycochemical contents, antioxidant and cytotoxic activities and compound
      screening of the cultivated tuber with the wild tuber. Results showed an increase
      in carbohydrate content by 45.81% and protein content by 123.68% in the
      cultivated tuber while fat content reduced by 13.04%. Cultivated tuber also
      showed an increase of up to 64.21% for total flavonoid-like compounds and 62.51%
      of total beta-D-glucan compared to the wild tuber. The antioxidant activity of
      cultivated tuber and wild tuber was 760 and 840 ug mL-1, respectively. The
      cytotoxic activity of boiled water extract of cultivated tuber against a human
      lung cancer cell line (A549) was 65.50 +/- 2.12 ug mL-1 and against a human
      breast cancer cell line (MCF7) was 19.35 +/- 0.11 ug mL-1. beta-D-glucan extract
      from the purification of boiled water extract of cultivated tuber showed
      cytotoxic activity at 57.78 +/- 2.29 ug mL-1 against A549 and 33.50 +/- 1.41 ug
      mL-1 against MCF7. However, the beta-glucan extract from wild tuber did not show
      a cytotoxic effect against either the A549 or MCF7 cell lines. Also, neither of
      the extracts from cultivated tuber and wild tuber showed an effect against a
      normal cell line (MRC5). Compound profiling through by liquid chromatography mass
      spectrometry (LC/MS) showed the appearance of new compounds in the cultivated
      tuber. In conclusion, our cultivated tuber of tiger's milk mushroom using a new
      recipe cultivation technique showed improved nutrient and bioactive compound
      contents, and antioxidant and cytotoxic activities compared to the wild tuber.
      Further investigations are required to obtain a better quality of cultivated
      tuber.

PMID- 29204734
TI  - Basic concepts in metal work failure after metastatic spine tumour surgery.
AB  - PURPOSE: The development of spinal implants marks a watershed in the evolution of
      metastatic spine tumour surgery (MSTS), which has evolved from standalone
      decompressive laminectomy to instrumented stabilization and decompression with
      reconstruction when necessary. Fusion may not be feasible after MSTS due to poor
      quality of graft host bed along with adjunct chemotherapy and/or radiotherapy
      postoperatively. With an increase in the survival of patients with spinal
      tumours, there is a probability of an increase in the rate of implant failure.
      This review aims to help establish a clear understanding of implants/constructs
      used in MSTS and to highlight the fundamental biomechanics of implant/construct
      failures. METHODS: Published literature on implant failure after spine surgery
      and MSTS has been reviewed. The evolution of spinal implants and their role in
      MSTS has been briefly described. The review defines implant/construct failures
      using radiological parameters that are practical, feasible, and derived from
      historical descriptions. We have discussed common modes of implant/construct
      failure after MSTS to allow further understanding, interception, and prevention
      of catastrophic failure. RESULTS: Implant failure rates in MSTS are in the range
      of 2-8%. Variability in patterns of failure has been observed based on anatomical
      region and the type of constructs used. Patients with construct/implant failures
      may or may not be symptomatic and present either as early (< 3months) or late
      failures (> 3months). It has been noted that not all the implant failures after
      MSTS result in revisions. CONCLUSION: Based on the observed radiological criteria
      and clinical presentations, we have proposed a clinico-radiological
      classification for implant/construct failure after MSTS.

PMID- 29204735
TI  - Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of
      proinflammatory cytokine and TRP channel expression.
AB  - PURPOSE: To investigate and compare the occurrence of inflammatory processes in
      the sites of disc degeneration in the lumbar and cervical spine by a gene array
      and subsequent qPCR and to investigate the mechanistic involvement of transient
      receptor potential channels TRPC6 and TRPV4. METHODS: The gene expression of
      inflammatory cytokines and TRP channels was measured in human disc samples
      obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar
      (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and
      analyzed for differences with regard to spinal level, IVD degeneration grade,
      Modic grade, age, sex, disc region and surgical extent. RESULTS: Aside from genes
      with known implication in DDD and DH, four previously unreported genes from the
      interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A
      correlation between gene expression and age (IL-15) and IVD degeneration grade
      (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant
      differences were detected between cervical and lumbar discs (IL-15), nucleus and
      annulus (IL-6, TNF-alpha, TRPC6), single-level and multi-level surgery (IL-6, IL
      8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair
      correlations, either between different cytokines or between cytokines and TRP
      channels, exist in the disc. CONCLUSION: This study supports the relevance of IL
      6 and IL-8 in disc diseases, but furthermore points toward a possible
      pathological role of IL-15 and type I interferons, as well as a mechanistic role
      of TRPC6. With limited differences in the inflammatory profile of cervical and
      lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the
      treatment of disc pathologies may be applicable independent of the spinal region.

PMID- 29204736
TI  - Effect of bacterial lipopolysaccharides on morphogenetic activity in wheat
      somatic calluses.
AB  - We evaluated the effect of lipopolysaccharides from the plant-growth-promoting
      associative bacterium Azospirillum brasilense Sp245 and from the enteric
      bacterium Escherichia coli K12 on the morphogenic potential of in vitro-growing
      somatic calluses of soft spring wheat (Triticum aestivum L. cv. Saratovskaya 29).
      A genetic model was used that included two near-isogenic lines of T. aestivum L.
      cv. Saratovskaya 29 with different embryogenic capacities; one of these lines
      carries the Rht-B1 dwarfing gene, whereas the other lacks it. When added to the
      nutrient medium, the lipopolysaccharide of A. brasilense Sp245 promoted the
      formation of calluses with meristematic centers and stimulated the regeneration
      ability of the cultured tissues in both lines. By contrast, the
      lipopolysaccharide of the enteric bacterium E. coli K12 barely affected the
      morphogenetic activity of callus cells and the yield of morphogenic calluses and
      regenerated plants. These findings indicate that the lipopolysaccharide of the
      plant-growth-promoting associative bacterium A. brasilense Sp245 specifically
      enhances the morphogenetic activity of wheat somatic tissues, which increases the
      efficacy of culturing of genotypes with a relatively low morphogenic potential.
      The results of the study may contribute to the improvement of the efficacy of
      plant cell selection and gene engineering and to a better understanding of the
      mechanisms responsible for plant recognition of lipopolysaccharides of
      associative bacteria.

PMID- 29204737
TI  - Initial Slovenian experience with MitraClip therapy : Careful selection of
      patients is crucial for optimal outcome.
AB  - BACKGROUND: MitraClip is a percutaneous mitral repair technology increasingly
      used for high surgical risk patients with primary or secondary mitral
      regurgitation. We describe initial Slovenian experience with MitraClip and
      discuss the importance of identifying the suitable candidates for this procedure.
      METHODS: We retrospectively analyzed the first 10 patients (mean age 75.6 +/- 6.9
      years, logistic Euroscore 28.4 +/- 10.9%) with severe and moderate to severe
      mitral regurgitation (8 secondary, 1 primary and 1 mixed etiology) who underwent
      a MitraClip procedure between January 2015 and February 2017. RESULTS: Acute
      reduction of mitral regurgitation was achieved in all but one patient (90%).
      There were no periprocedural mortalities and at short to mid-term follow-up
      (median 12 months, interquartile range 3-15 months). In eight patients
      improvement of functional class was observed at discharge. No functional
      improvement was achieved in a patient with advanced ischemic cardiomyopathy, and
      in a patient with degenerative mitral disease in whom the MitraClip procedure had
      failed necessitating mitral valve surgery. One patient experienced late leaflet
      detachment and was effectively managed with a second MitraClip procedure. There
      were two vascular complications at the access site and one percutaneous closure
      of an iatrogenic atrial septal defect. CONCLUSION: Our initial experiences with a
      small number of patients indicate that percutaneous mitral repair with MitraClip
      is a feasible and safe method in high-risk patients. Special attention should be
      paid to careful patient selection including detailed echocardiographic evaluation
      of mitral valve anatomy, technical performance and final result, particularly at
      the beginning of the learning curve in order to reduce the rate of serious
      complications.

PMID- 29204738
TI  - The Association Between Myocardial Fibrosis and Depressed Capillary Density in
      Rat Model of Left Ventricular Hypertrophy.
AB  - Myocardial fibrogenesis is initiated once the coordination between oxygen supply
      and demand is disrupted in pressure overload-induced cardiac hypertrophy.
      Clinical observations showed that myocardial fibrosis did not evenly occur in the
      hypertrophic myocardium. The present study was undertaken to specifically address
      differential vulnerabilities to fibrogenesis of different regions in the
      myocardium subjected to pressure overload-induced hypertrophy. SD rats were
      divided into two groups, sham-operated control and ascending artery constriction
      induced cardiac hypotrophy. Thirty-four weeks after surgery, rats were sacrificed
      and hearts were harvested. Myocardial tissues were processed and sequentially
      sectioned for detection of collagen deposition, myocyte hypertrophy and vascular
      density analysis. Redundant collagen stained with Sirius red and anti-collagen I
      antibody was found in the extracellular matrix, but high volume of collagen
      fraction was largely localized more in posterior and lateral walls than in
      anterior wall and interventricular septum, which is in accordance with the
      accumulation of fibroblasts. In association with the differential regional
      collagen accumulation, the cardiomyocytes were more hypertrophic in the posterior
      and lateral wall than the other left ventricle. However, the capillary density in
      the lateral and posterior walls was significantly decreased. The results
      indicated that the posterior and lateral walls were more vulnerable to
      fibrogenesis post-pressure overload-induced cardiac hypertrophy, which was
      associated with the depressed angiogenesis in these two regions.

PMID- 29204739
TI  - Serological evidence of H5-subtype influenza A virus infection in indigenous
      avian and mammalian species in Korea.
AB  - In Korea, H5-subtype highly pathogenic avian influenza (HPAI) has caused huge
      economic losses in poultry farms through outbreaks of H5N1 since 2003, H5N8 since
      2013 and H5N6 since 2016. Although it was reported that long-distance migratory
      birds may play a major role in the global spread of avian influenza viruses
      (AIVs), transmission from such birds to poultry has not been confirmed.
      Intermediate hosts in the wild also may be a potential factor in viral
      transmission. Therefore, a total of 367 serum samples from wild animals were
      collected near major migratory bird habitats from 2011 to 2016 and tested by AIV
      specific blocking ELISA and hemagglutination inhibition (HI) test. Two mammalian
      and eight avian species were seropositive according to the ELISA test. Among
      these, two mammalian (Hydropotes inermis and Prionailurus bengalensis) and three
      avian (Aegypius monachus, Cygnus cygnus, and Bubo bubo) species showed high HI
      titres (> 1,280) against one or two H5-subtype AIVs. As H. inermis (water deer),
      P. bengalensis (leopard cat), and B. bubo (Eurasian eagle owl) are indigenous
      animals in Korea, evidence of H5-subtype AIV in these animals implies that
      continuous monitoring of indigenous animals should be followed to understand
      interspecies transmission ecology of H5-subtype influenza viruses.

PMID- 29204740
TI  - Living with conduct problem youth: family functioning and parental perceptions of
      their child.
AB  - Parenting children with conduct problems (CP) is challenging, yet very little is
      known about the impact of the child's behaviour on family functioning or how
      parents of children with CP perceive their child. The aim of this research was to
      examine whether families with children with CP and high vs. low levels of callous
      unemotional traits (HCU vs. LCU) experience differences in family functioning and
      parental perceptions. One hundred and one parents/caregivers of boys aged 11-16
      [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] completed the
      McMaster Family Assessment Device, measuring multiple domains of family
      functioning. Parents/caregivers also completed a written statement describing
      their child, used for qualitative analysis. Families with CP/HCU children had
      poorer affective involvement than TD (p = 0.00; d = - 1.17) and CP/LCU (p = 0.03;
      d = - 0.62) families. Families with CP/HCU children showed significantly poorer
      general family functioning (p = 0.04; d = - 0.63) and more poorly defined family
      roles (p = 0.005; d = - 0.82) than families with TD children. Qualitative
      analyses indicated that parents/caregivers of CP/HCU children characterised them
      as having a dichotomous personality and being superficially charming. CP/LCU
      children were characterised as cheeky and endearing, with parents reporting good
      rapport. Families with CP/HCU children presented with specific difficulties in
      affective involvement and parents described challenges which were in line with
      the child's specific presentation of lack of empathy and shallow affect. These
      findings may be used to help clinicians identify targets for family
      interventions.

PMID- 29204741
TI  - Effects of zinc on the production of alcohol by Clostridium carboxidivorans P7
      using model syngas.
AB  - Renewable energy, including biofuels such as ethanol and butanol from syngas
      bioconversed by Clostridium carboxidivorans P7, has been drawing extensive
      attention due to the fossil energy depletion and global eco-environmental issues.
      Effects of zinc on the growth and metabolites of C. carboxidivorans P7 were
      investigated with model syngas as the carbon source. The cell concentration was
      doubled, the ethanol content increased 3.02-fold and the butanol content
      increased 7.60-fold, the hexanol content increased 44.00-fold in the medium with
      280 MUM Zn2+, when comparing with those in the control medium [Zn2+, (7 MUM)].
      Studies of the genes expression involved in the carbon fixation as well as acid
      and alcohol production in the medium with 280 MUM Zn2+ indicated that fdhII was
      up-regulated on the second day, acs A, fdhII, bdh35 and bdh50 were up-regulated
      on the third day and bdh35, acsB, fdhI, fdhIII, fdhIV, buk, bdh10, bdh35, bdh40
      and bdh50 were up-regulated on the fourth day. The results indicated that the
      increased Zn2+ content increased the alcohol production through increase in the
      gene expression of the carbon fixation and alcohol dehydrogenase.

PMID- 29204742
TI  - Target and Tissue Selectivity Prediction by Integrated Mechanistic
      Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.
AB  - Selectivity is an important attribute of effective and safe drugs, and prediction
      of in vivo target and tissue selectivity would likely improve drug development
      success rates. However, a lack of understanding of the underlying
      (pharmacological) mechanisms and availability of directly applicable predictive
      methods complicates the prediction of selectivity. We explore the value of
      combining physiologically based pharmacokinetic (PBPK) modeling with quantitative
      structure-activity relationship (QSAR) modeling to predict the influence of the
      target dissociation constant (K D) and the target dissociation rate constant on
      target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL
      database are predicted by QSAR random forest (RF) modeling for the CB1 receptor
      and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant,
      CP-55940, and Delta8-tetrahydrocanabinol, one of the active ingredients of
      cannabis, were selected for simulations of target occupancy for CB1, TRPV1,
      mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the
      combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling
      demonstrated that the optimal values of the K D and k off for target and tissue
      selectivity were dependent on target concentration and tissue distribution
      kinetics. Interestingly, if the target concentration is high and the perfusion of
      the target site is low, the optimal K D value is often not the lowest K D value,
      suggesting that optimization towards high drug-target affinity can decrease the
      benefit-risk ratio. The presented integrative structure-pharmacokinetic
      pharmacodynamic modeling provides an improved understanding of tissue and target
      selectivity.

PMID- 29204743
TI  - Genetic Variation and Gene Expression Levels of Tight Junction Genes Indicates
      Relationships Between PTEN as well as MAGI1 and Microscopic Colitis.
AB  - BACKGROUND AND AIM: Microscopic colitis (MC) has been associated with increased
      paracellular permeability. Therefore, we aimed to investigate potential
      associations between MC and several genes encoding tight junction (TJ) proteins
      reported to interact with each other. METHODS: The association between MC and
      single nucleotide polymorphisms (SNP; n = 63) within TJ genes (F11R, MAGI1,
      MAGI2, MAGI3, PARD3, PTEN, and TJP1) were investigated in a case-control study (n
      MC patients = 104 and n controls = 423). The genes that exhibited an association
      with MC were further investigated for gene expression related to genotype, MC
      phenotype, and gender using colonic biopsies from MC patients (n = 25) and
      controls (n = 58). RESULTS: Based on the number of investigated genes and after
      correction for multiple testing, an association was detected between a SNP marker
      in PTEN (rs1234224) and both MC overall (OR = 1.70, 95% CI 1.23-2.34, p = 0.001)
      and collagenous colitis (CC; OR = 1.79, 95% CI 1.22-2.62, p = 0.003). Further,
      SNP markers in MAGI1 (rs17417230) and F11R (rs790055) were associated with MC
      overall (OR = 1.58, 95% CI 1.14-2.19, p = 0.006) and with CC (OR = 2.58, 95% CI
      1.27-5.25, p = 0.007), respectively. However, none of the associated SNPs
      contributed markedly to the expression of the respective genes. Nonetheless,
      decreased MAGI1 (p = 3.47 * 10-4) and PTEN (p = 0.004) expression was associated
      with lymphocytic colitis (LC) and CC, respectively, compared to controls.
      CONCLUSIONS: Decreased expression of PTEN and MAGI1 in the colonic mucosa might
      contribute to the pathogenesis of MC and its sub-phenotypes. Furthermore, our
      study indicates that genetic variants of TJ components are predisposing factors
      in the etiology of MC. Finally, F11R, MAGI1, and PTEN are new candidate genes
      that exhibit an association with MC.

PMID- 29204744
TI  - EUS-Guided Pancreatic Duct Puncture for Difficult Cannulation of Stenosed
      Pancreaticojejunostomy.

PMID- 29204745
TI  - Heterogeneity and function of hippocampal macroglia.
AB  - The contribution of glial cells to normal and impaired hippocampal function is
      increasingly being recognized, although important questions as to the mechanisms
      that these cells use for their crosstalk with neurons and capillaries are still
      unanswered or lead to controversy. Astrocytes in the hippocampus are
      morphologically variable and a single cell contacts with its processes more than
      100,000 synapses. They predominantly express inward rectifier K+ channels and
      transporters serving homeostatic function but may also release gliotransmitters
      to modify neuronal signaling and brain circulation. Intracellular Ca2+ transients
      are key events in the interaction of astrocytes with neurons and the vasculature.
      Hippocampal NG2 glia represent a population of cells with proliferative capacity
      throughout adulthood. Intriguingly, they receive direct synaptic input from
      pyramidal neurons and interneurons and express a multitude of ion channels and
      receptors. Despite in-depth knowledge about the features of these transmembrane
      proteins, the physiological impact of NG2 glial cells and their synaptic input
      remain nebulous. Because of the low abundance of oligodendrocytes in the
      hippocampus, limited information is available about their specific properties.
      Given the multitude of signaling molecules expressed by the various types of
      hippocampal glial cells (and because of space constraints), we focus, in this
      review, on those properties that are considered key for the interaction of the
      respective cell type with its neighborhood.

PMID- 29204746
TI  - Comparative analysis of human Wharton's jelly mesenchymal stem cells derived from
      different parts of the same umbilical cord.
AB  - Easy isolation, lack of ethical issues, high proliferation, multi-lineage
      differentiation potential and immunomodulatory properties of umbilical cord (UC)
      derived mesenchymal stem cells (MSCs) make them a valuable tool in stem cell
      research. Recently, Wharton's jelly (WJ) was proven as the best MSC source among
      various compartments of UC. However, it is still unclear whether or not Wharton's
      jelly-derived MSCs (WJMSCs) from different parts of the whole cord exhibit the
      same characteristics. There may be varied MSCs present in different parts of WJ
      throughout the length of the UC. For this purpose, using an explant attachment
      method, WJMSCs were isolated from three different parts of the UC, mainly present
      towards the placenta (mother part), the center of the whole cord (central part)
      and the part attached to the fetus (baby part). WJMSCs from all three parts were
      maintained in normal growth conditions (10% ADMEM) and analyzed for mesenchymal
      markers, pluripotent genes, proliferation rate and tri-lineage differentiation
      potential. All WJMSCs were highly proliferative, positively expressed CD90,
      CD105, CD73 and vimentin, while not expressing CD34, CD45, CD14, CD19 or HLA-DR,
      differentiated into adipocytes, osteocytes and chondrocytes and expressed
      pluripotency markers OCT-4, SOX-2 and NANOG at gene and protein levels.
      Furthermore, MSCs derived from all the parts were shown to have potency towards
      hepatocyte-like cell differentiation. Human bone marrow-derived MSCs were used as
      a positive control. Finally, we conclude that WJMSCs derived from all the parts
      are valuable sources and can be efficiently used in various fields of
      regenerative medicine.

PMID- 29204747
TI  - Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus
      aureus.
AB  - Humans are well equipped to defend themselves against bacteria. The innate immune
      system employs diverse mechanisms to recognize, control and initiate a response
      that can destroy millions of different microbes. Microbes that evade the
      sophisticated innate immune system are able to escape detection and could become
      pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are
      particularly successful due to the development of a wide variety of virulence
      strategies for bacterial pathogenesis and they invest significant efforts towards
      mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular
      defense and can rapidly kill invading microbes, which is an indispensable
      function for maintaining host health. This review compares the key features of
      Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a
      specific focus on virulence mechanisms utilized to evade neutrophils in bacterial
      pathogenesis. It is important to understand the complex interactions between
      pathogenic bacteria and neutrophils so that we can disrupt the ability of
      pathogens to cause disease.

PMID- 29204748
TI  - Imaging the expression of glypican-3 in hepatocellular carcinoma by PET.
AB  - The glypican-3 (GPC3) receptor is overexpressed in hepatocellular carcinoma (HCC)
      and is a potential diagnostic and therapeutic target. GPC3-targeted molecular
      imaging will be helpful to differentiate diagnosis and guide therapy. In the
      present study, we will develop a novel PET probe for imaging the expression of
      GPC-3. L5 (sequence: RLNVGGTYFLTTRQ), a GPC3 targeting peptide, was labeled with
      5-carboxyfluorescein (FAM) and 18F-fluoride. Cell binding tests were performed to
      identify the binding specificity of FAM-L5 and 18F radiolabeled peptide.
      MicroPET/CT imaging was used to determine the potential of a novel PET tracer for
      visualizing HCC tumors with a high expression of GPC3. In vitro binding tests
      showed that the uptake of FAM-L5 in HepG2 cells (high expression of GPC3) was
      significantly higher than that of HL-7702 cells (negative expression of GPC3)
      (mean fluorescent intensity: 14,094 +/- 797 vs. 2765 +/- 314 events, t = 32.363,
      P = 0.000). Confocal fluorescent imaging identified that FAM-L5 accumulated where
      the GPC3 receptor was located. A novel PET tracer (18F-AlF-NODA-MP-6-Aoc-L5) was
      successfully labeled by chelation chemistry. In vitro cell uptake studies showed
      that 18F-AlF-NODA-MP-6-Aoc-L5 can bind to HepG2 tumor cells and was stable in PBS
      and mouse serum stability tests. MicroPET/CT showed that HepG2 tumors could be
      clearly visualized with a tumor/muscle ratio of 2.46 +/- 0.53. However, the
      tumor/liver ratio was low (0.93 +/- 0.16) due to the high physiological uptake in
      the liver. This study demonstrates that FAM and the 18F-labeled L5 peptide can
      selectively target HCC with a high expression of GPC3 in vitro and in vivo. 18F
      AlF-NODA-MP-C6-L5 has the potential to be a GPC3 target tracer but requires some
      chemical modifications to achieve a high enough tumor/liver ratio for detection
      of the tumor in the liver.

PMID- 29204749
TI  - Phosphorylation of pyridoxal 5'-phosphate enzymes: an intriguing and neglected
      topic.
AB  - Pyridoxal 5'-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions
      of amino acids and amines, with the exception of glycogen phosphorylase which
      exhibits peculiar both substrate preference and chemical mechanism. They
      represent about 4% of the gene products in eukaryotic cells. Although structure
      function investigations regarding these enzymes are copious, their regulation by
      post-translational modifications is largely unknown. Protein phosphorylation is
      the most common post-translational modification fundamental in mediating diverse
      cellular functions. This review aims at summarizing the current knowledge on
      regulation of PLP enzymes by phosphorylation. Starting from the paradigmatic PLP
      dependent glycogen phosphorylase, the first phosphoprotein discovered, we collect
      data in literature regarding functional phosphorylation events of eleven PLP
      enzymes belonging to different fold types and discuss the impact of the
      modification in affecting their activity and localization as well as the
      implications on the pathogenesis of diseases in which many of these enzymes are
      involved. The pivotal question is to correlate the structural consequences of
      phosphorylation among PLP enzymes of different folds with the functional
      modifications exerted in terms of activity or conformational changes or others.
      Although the literature shows that the phosphorylation of PLP enzymes plays
      important roles in mediating diverse cellular functions, our recapitulation of
      clue findings in the field makes clear that there is still much to be learnt.
      Besides mass spectrometry-based proteomic analyses, further biochemical and
      structural studies on purified native proteins are imperative to fully understand
      and predict how phosphorylation regulates PLP enzymes and to find the
      relationship between addition of a phosphate moiety and physiological response.

PMID- 29204750
TI  - Protective Effects of Fisetin Against 6-OHDA-Induced Apoptosis by Activation of
      PI3K-Akt Signaling in Human Neuroblastoma SH-SY5Y Cells.
AB  - 6-Hydroxydopamine (6-OHDA) induces the production of reactive oxygen species
      (ROS) that are associated with various neurodegenerative diseases such as
      Parkinson's disease. 3,3',4',7-Tetrahydroxyflavone (fisetin), a plant flavonoid
      has a variety of physiological effects such as antioxidant activity. In this
      study, we investigated the molecular mechanism of the neuroprotective effects of
      fisetin against 6-OHDA-induced cell death in human neuroblastoma SH-SY5Y cells. 6
      OHDA-mediated cell toxicity was reduced in a fisetin concentration-dependent
      manner. 6-OHDA-mediated elevation of the expression of the oxidative stress
      related genes such as hemeoxygenase-1, NAD(P)H dehydrogenase quinone 1, NF-E2
      related factor 2, and gamma-glutamate-cysteine ligase modifier was suppressed by
      fisetin. Fisetin also lowered the ratio of the proapoptotic Bax protein and the
      antiapoptotic Bcl-2 protein in SH-SY5Y cells. Moreover, fisetin effectively
      suppressed 6-OHDA-mediated activation of caspase-3 and caspase-9, which leads to
      the cell death, while, 6-OHDA-induced caspase-3/7 activity was lowered.
      Furthermore, fisetin activated the PI3K-Akt signaling, which inhibits the caspase
      cascade, and fisetin-mediated inhibition of 6-OHDA-induced cell death was negated
      by the co-treatment with an Akt inhibitor. These results indicate that fisetin
      protects 6-OHDA-induced cell death by activating PI3K-Akt signaling in human
      neuronal SH-SY5Y cells. This is the first report that the PI3K-Akt signaling is
      involved in the fisetin-protected ROS-mediated neuronal cell death.

PMID- 29204751
TI  - Opening new avenues for plant developmental research.

PMID- 29204752
TI  - Monitoring circadian rhythms of individual cells in plants.
AB  - The circadian clock is an endogenous timing system based on the self-sustained
      oscillation in individual cells. These cellular circadian clocks compose a
      multicellular circadian system working at respective levels of tissue, organ,
      plant body. However, how numerous cellular clocks are coordinated within a plant
      has been unclear. There was little information about behavior of circadian clocks
      at a single-cell level due to the difficulties in monitoring circadian rhythms of
      individual cells in an intact plant. We developed a single-cell bioluminescence
      imaging system using duckweed as the plant material and succeeded in observing
      behavior of cellular clocks in intact plants for over a week. This imaging
      technique quantitatively revealed heterogeneous and independent manners of
      cellular clock behaviors. Furthermore, these quantitative analyses uncovered the
      local synchronization of cellular circadian rhythms that implied phase-attractive
      interactions between cellular clocks. The cell-to-cell interaction looked to be
      too weak to coordinate cellular clocks against their heterogeneity under constant
      conditions. On the other hand, under light-dark conditions, the heterogeneity of
      cellular clocks seemed to be corrected by cell-to-cell interactions so that
      cellular clocks showed a clear spatial pattern of phases at a whole plant level.
      Thus, it was suggested that the interactions between cellular clocks was an
      adaptive trait working under day-night cycles to coordinate cellular clocks in a
      plant body. These findings provide a novel perspective for understanding spatio
      temporal architectures in the plant circadian system.

PMID- 29204753
TI  - Phloem differentiation: an integrative model for cell specification.
AB  - Plant vasculature consists of two major conductive cell types, xylem tracheary
      elements and phloem sieve elements (SEs). Both cell types undergo a highly
      specialized differentiation process. The root meristem of Arabidopsis displays a
      stereotypical anatomy in which the central vasculature is surrounded by
      concentric layers of outer tissues. Each cell file is derived from stem cells
      located in the root tip. A series of formative and proliferative divisions take
      place in the meristem; these are followed by cell expansion and differentiation.
      Protophloem differentiation is unique in being complete only 20-25 cells away
      from the first stem cell, and during the differentiation process the cells lose
      several organelles, including the nucleus, while the remaining organelles are
      rearranged. Defects in SE development have been shown to result in impaired auxin
      transport and response and therefore systemically affect root growth. Although a
      few genes have been demonstrated to function in phloem development, detailed
      analyses and a comprehensive understanding of sieve element development (i.e. how
      often the stem cells divide, how frequently enucleation takes place, and how SE
      development is coordinated between cell division and differentiation on a
      molecular level) are still lacking. Advanced live-imaging techniques which enable
      prolonged time-lapse captures of root tip growth as well as single-cell
      transcriptomic analysis of the 20-25 cells in the SE file could help resolve
      these questions. In addition, understanding the interplay between the PLETHORA
      (PLT) gradient, which is known to govern the root zonation, and phloem
      development within the root meristem could shed light on the rapidity of SE
      differentiation and its importance to the meristem.

PMID- 29204755
TI  - Teaching Empathy: the Implementation of a Video Game into a Psychiatry Clerkship
      Curriculum.
AB  - OBJECTIVE: Empathy plays an important role for physicians, but the literature
      demonstrates that it often deteriorates during medical school. The purpose of
      this study is to investigate the use of the interactive video game "That Dragon,
      Cancer" as a tool to teach empathy to third-year medical students. METHODS: The
      authors gave a modified, Jefferson Scales of Physician Empathy (JSPE) to 84 third
      year medical students in their psychiatry clerkship before and after they played
      and completed "That Dragon, Cancer" during the 2016-2017 academic calendar year.
      RESULTS: The average level of empathy in the students as measured by least
      squares means of the answers to the truncated JSPE improved after playing through
      "That Dragon, Cancer" (5.7738 vs 6.2322, p < 0.0001). The majority of students
      agreed that learning empathy through video games was preferable and more
      effective than traditional didactics. CONCLUSIONS: Interactive video games such
      as "That Dragon, Cancer" may be useful as part of innovative curricula to improve
      empathy among third-year medical students.

PMID- 29204756
TI  - The PRITE Examinations: Background and Future Directions.

PMID- 29204754
TI  - The Na+/Cl--Coupled, Broad-Specific, Amino Acid Transporter SLC6A14 (ATB0,+):
      Emerging Roles in Multiple Diseases and Therapeutic Potential for Treatment and
      Diagnosis.
AB  - Amino acids are essential building blocks of all mammalian cells, and amino acid
      transporters play a vital role in transporting them into cells and their further
      distribution among the various cellular compartments. There are ~ 430 known
      transporters in the solute-linked carrier (SLC) gene family, divided into 52
      distinct families. Eleven of these gene families contain one or more amino acid
      transporters. These transporters differ significantly from each other in terms of
      substrate specificity, ion dependence, and energetics. Given the variety of roles
      they fulfill in human physiology, it is not surprising that a number of diseases
      are associated with the malfunction of these transporters. In particular, as
      amino acids are critical for cell growth, survival, and proliferation, the role
      of amino acid transporters in cancer is gaining increasing attention in recent
      years. The present review primarily focuses on one particular amino acid
      transporter, SLC6A14 (also known as ATB0,+), with regard to its relevance to
      specific diseases, including cancer, and the molecular mechanisms underlying the
      disease-related alterations in the expression of the transporter. Furthermore,
      the review highlights the possible utility of this transporter in drug delivery
      and also its therapeutic potential for the treatment and diagnosis of cancer.

PMID- 29204757
TI  - Prevalence of comorbidities and evaluation of screening in Chinese patients with
      spondyloarthritis.
AB  - The aim of the study was to determine whether the presence of spondyloarthritis
      (SpA) is associated with particular comorbidities and evaluate the prevalence of
      comorbidities, risk factors, and monitoring status in China. Three hundred forty
      six patients fulfilling ASAS criteria for SpA were recruited from the Third
      Affiliated Hospital of Sun Yat-sen University. The prevalence of comorbidities
      and percentage of patients optimally monitored for comorbidities were calculated.
      The most frequent comorbidities were osteoporosis (31.0%) and hepatitis B virus
      infection (18.5%). Only 1 patient was found to have active tuberculosis. Several
      cancer screenings were performed in very few patients. Among 45 patients ever
      exposed to a biological DMARDs, 35 (77%) and 36 (80%) underwent a screening test
      for viral hepatitis and tuberculosis. Among patients without a history of
      hypertension, elevated blood pressure was detected in 5.8% of the patients.
      Hyperglycemia and hyperlipidemia were also found in patients during the study.
      One hundred twenty-two (35.3%) of the 346 patients never had either calcium or
      vitamin D for prevention of osteoporosis. Patients with SpA have high risks of
      comorbidities but have not monitored properly. More attention should be paid for
      systematic screening and an early detection of comorbidities in patients with
      SpA.

PMID- 29204758
TI  - Antiphospholipid antibodies, steroid dose, arterial hypertension, relapses, and
      late-onset predict organ damage in a population of Colombian patients with
      systemic lupus erythematosus.
AB  - Organ damage predicts mortality, increased accrual of detriment, and poor quality
      of life in systemic lupus erythematosus patients. The objective of this study is
      to determine the damage-free survival and its predictive factors in a population
      of Colombian subjects. The method used in this study is the retrospective follow
      up of a cohort; damage was measured with SLICC/ACR index. Predictors of
      impairment were assessed by logistic regression and survival analysis. One
      hundred sixty-one individuals were included; 28.9% suffered damage, primarily
      neuropsychiatric, renal, and vascular. Arterial hypertension, antiphospholipid
      antibodies, prednisone dose, and number of relapses were all predictors of
      detriment. Onset after age 50 and daily prednisone dose higher than 7.5 mg
      determined earlier occurrence of damage.

PMID- 29204759
TI  - Ocular manifestations of IgG4-related disease in children. More common than
      anticipated? Review of the literature and case report.
AB  - IgG4-related disease (IgG4-RD) is an entity with various clinical manifestations.
      Histopathologically, it is characterized by lymphoplasmacytic infiltrates
      enriched in IgG4 (+) plasmacytes and usually fibrosis of the affected tissue.
      Most of the patients have also increased IgG4 serum levels and they respond to
      glucocorticosteroids. In children, due to its rare occurrence, IgG4-RD is ill
      defined. From the published studies, so far, it appears that ocular
      manifestations are very common in the paediatric population with IgG4-RD. Herein,
      we describe a new case of a child with IgG4-RD with ocular involvement manifested
      with orbit and eyelid swelling, successfully treated with steroids. In addition,
      we review the clinical, laboratory, histopathologic and radiologic
      characteristics of the published paediatric cases with IgG4-RD and ocular
      involvement, critically comparing them with the characteristics of the adult
      population. It seems that ocular manifestations are more frequently observed in
      children than in adults. Also, the pattern of involvement is different, with
      extraocular muscles and soft tissues being more commonly affected than the
      lacrimal glands.

PMID- 29204760
TI  - The DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire:
      development and preliminary testing of a new tool to screen patients with
      inflammatory bowel disease for the presence of spondyloarthritis.
AB  - To develop and to test in a preliminary way a new self-administered screening
      tool, called DETection of Arthritis in Inflammatory boweL diseases (DETAIL)
      questionnaire, in patients suffering from inflammatory bowel disease (IBD) not
      previously diagnosed as having a spondyloarthritis (SpA). DETAIL questionnaire
      was realized through the interrogation of 95 experts. They were asked to rate the
      importance of a list of items, derived from a review of the referral models of
      SpA, to detect the SpA manifestations in IBD patients. The six top-rated items
      composed the questionnaire, tested in IBD patients not already diagnosed having a
      SpA. One-hundred and twenty-eight patients were tested with the DETAIL
      questionnaire in the gastroenterology setting. After the rheumatologic
      assessment, in 21 (16.4%) subjects was diagnosed a SpA according to the
      Assessment of SpondyloArthritis international Society (ASAS) classification
      criteria. Of the six items of the DETAIL questionnaire, the best positive
      likelihood ratio (LR+) was found in item 2 (LR+ 3.82), exploring dactylitis, and
      in item 6 (LR+ 3.82) and item 5 (LR+ 3.40), two questions exploring inflammatory
      low back pain. Enthesitis (item 3-LR+ 2.87) and peripheral synovitis (item 1 -
      LR+ 2.81) gave similar results, while item 4, exploring the duration of low back
      pain, resulted in the worst performance (LR+ 1.99). Three of the six items
      answered in affirmative way gave a post-test probability >= 75%. The presence of
      a fibromyalgia represents a major confounder. The DETAIL questionnaire showed
      good screening properties that need to be confirmed in broader cohorts.

PMID- 29204762
TI  - Magnetic resonance imaging (MRI) of feet demonstrates subclinical inflammatory
      joint disease in cutaneous psoriasis patients without clinical arthritis.
AB  - We evaluated inflammation at the small joints of feet in psoriasis patients
      without clinical arthritis (PsO) as against clinically overt psoriatic arthritis
      (PsA) patients, using a low field magnet extremity MRI (eMRI). Patients with
      psoriasis recruited from dermatology and rheumatology clinics of a tertiary care
      institution in southern India were divided into PsO and PsA groups. Demographic
      and physical examination details were recorded. Consenting patients underwent non
      contrast eMRI of the right foot. Two trained readers scored the MRI parameters of
      inflammation (synovitis, tenosynovitis, osteitis) using a modification of the PsA
      magnetic resonance imaging score (PsAMRIS). Proportion of patients with any sign
      of MRI inflammation was noted. Clinical variables were compared with inflammation
      scores for any association. A total of 83 patients (30 PsA and 53 PsO), with 75%
      males and mean age of 42.2 +/- 11.6 years were included. There was no statistical
      difference between the median eMRI inflammatory scores in PsA and PsO patients (p
      = 0.493). Evidence of inflammation was present in 33.9% and 50% patients in the
      PsO and PsA groups, respectively. Early arthritis for psoriatic patients
      screening questionnaire (EARP) score of >= 3 was significantly associated with
      imaging features of inflammation in PsO group (p = 0.044). This study
      corroborates a high proportion of subclinical inflammation in small joints of
      foot in PsO patients, which needs to be reproduced in larger, longitudinal
      cohorts to predict risk factors for progression to future PsA development.

PMID- 29204763
TI  - Automated Segmentation and Quantification of Drusen in Fundus and Optical
      Coherence Tomography Images for Detection of ARMD.
AB  - Age-related macular degeneration (ARMD) is one of the most common retinal
      syndromes that occurs in elderly people. Different eye testing techniques such as
      fundus photography and optical coherence tomography (OCT) are used to clinically
      examine the ARMD-affected patients. Many researchers have worked on detecting
      ARMD from fundus images, few of them also worked on detecting ARMD from OCT
      images. However, there are only few systems that establish the correspondence
      between fundus and OCT images to give an accurate prediction of ARMD pathology.
      In this paper, we present fully automated decision support system that can
      automatically detect ARMD by establishing correspondence between OCT and fundus
      imagery. The proposed system also distinguishes between early, suspect and
      confirmed ARMD by correlating OCT B-scans with respective region of the fundus
      image. In first phase, proposed system uses different B-scan based features along
      with support vector machine (SVM) to detect the presence of drusens and classify
      it as ARMD or normal case. In case input OCT scan is classified as ARMD, region
      of interest from corresponding fundus image is considered for further evaluation.
      The analysis of fundus image is performed using contrast enhancement and adaptive
      thresholding to detect possible drusens from fundus image and proposed system
      finally classified it as early stage ARMD or advance stage ARMD. The proposed
      system is tested on local data set of 100 patients with100 fundus images and 6800
      OCT B-scans. Proposed system detects ARMD with the accuracy, sensitivity, and
      specificity ratings of 98.0, 100, and 97.14%, respectively.

PMID- 29204761
TI  - Clinical value of systemic symptoms in IgA nephropathy with ANCA positivity.
AB  - Our aim was to evaluate the pathogenic role of anti-neutrophil cytoplasmic
      antibodies (ANCAs) in patients with IgA nephropathy (IgAN). A total of 2390
      patients with biopsy-confirmed IgAN were analyzed retrospectively. Thirty-five
      IgAN patients with ANCA and 40 IgAN patients without ANCA were enrolled.
      According to the Birmingham Vasculitis Activity Score (BVAS) items, the ANCA
      positive patients were further divided into two subgroups which with or without
      systemic symptoms. The cumulative renal survival rate was calculated using Kaplan
      Meier analysis. Comparisons between groups were made using the log rank test.
      Among the 35 ANCA-positive patients, 14 (40%) had systemic symptoms. Compared
      with ANCA-positive patients without systemic symptoms, ANCA-positive patients
      with systemic symptoms had a shorter duration of disease (1.0 [IQR, 0.3-6.8] vs.
      6.0 [IQR, 2.0-21.0], P = 0.011); showed worse renal function with lower levels of
      eGFR (24.2 [IQR, 11.7-74.9] vs. 100.1 [IQR, 59.6-130.2] mL/min/1.73 m2, P =
      0.002), serum albumin (30.4 [IQR, 27.4-34.8] vs. 41.5 [IQR, 35.1-44.4] g/L, P =
      0.001), and hemoglobin (96.1 +/- 21.5 vs. 118.2 +/- 22.4 g/L, P = 0.006); and
      presented relatively higher incidences of rapidly deteriorating kidney function
      (28.6 vs. 0.0%, P = 0.039) and moderate-to-severe tubular atrophy (78.6 vs.
      23.8%, P = 0.001). Kaplan-Meier analysis had shown that ANCA-positive patients
      with systemic symptoms had lower cumulative renal survival rate compared with
      both ANCA-positive patients without systemic symptoms and ANCA-negative patients
      (log rank = 14.40, P < 0.001). Evaluation of systemic symptoms is a simple,
      readily available clinical tool to predictive the pathogenic role of ANCA in
      IgAN.

PMID- 29204764
TI  - Variations in the origins of the thyroid arteries on CT angiography.
AB  - OBJECTIVE: To investigate the anatomical variations in the origins of the thyroid
      arteries on CT angiography images. METHODS: The presence and the origins of the
      superior thyroid artery, the inferior thyroid artery, and the thyroidea ima
      artery were retrospectively evaluated based on carotid CT angiography
      examinations. The bifurcation level of the common carotid artery with respect to
      the cervical vertebrae and disc spaces was also determined. A total of 640
      patients were included in the study. RESULTS: The right and left superior thyroid
      arteries arose from the external carotid artery in 413 (64.5%) and 254 (39.7%)
      patients, from the bifurcation of the common carotid artery in 131 (20.5%) and
      148 (23.1%) patients, and from the common carotid artery in 90 (14.1%) and 226
      (35.3%) patients, respectively. We could not observe the right and the left
      superior thyroid arteries in 6 (0.9%) and 12 (1.9%) of the patients,
      respectively. However, the right and left inferior thyroid arteries were not
      identified in 14 (2.2%) and 45 (7%) of the patients, respectively. The thyroidea
      ima artery was detected in 2.3% of the patients. CONCLUSION: The visualization of
      thyroid arteries on CT angiography images enables the anatomy of the arterial
      supply system of the thyroid gland to be explored in a noninvasive manner prior
      to surgery.

PMID- 29204765
TI  - Approaches to Multidimensional Health in Representations of Islamic Themes among
      Black Male Characters in American Film and Television.
AB  - Historically, representations of Islamic themes in media narratives of Black men
      have been characterized by personal transformations in the midst of surviving in
      crime-ridden inner city areas. These young Black men are usually at-risk due to
      their statuses as Black, economically disadvantaged men. Beginning with Malcolm X
      and Alex Haley's The Autobiography of Malcolm X, the Black male Islamic
      redemption narrative has become a common theme in Black popular culture, as it is
      usually supplemented with unique methods of confronting the various dimensions of
      health. Throughout this study, the representations of these approaches among
      Black men in contemporary film and television are examined throughout realms of
      spiritual, emotional, mental, physical, social, and vocational health.

PMID- 29204766
TI  - Correction to: Informing materials: drugs as tools for exploring cancer
      mechanisms and pathways.
AB  - The original version of this article unfortunately contained a mistake. Three
      entries are incorrect in the reference list. The corrected references are given
      below.

PMID- 29204767
TI  - Heterologous biosynthesis of triterpenoid ambrein in engineered Escherichia coli.
AB  - OBJECTIVES: To genetically engineer Escherichia coli for the heterologous
      biosynthesis of triterpenoid, ambrein, the main bioactive component of ambergris,
      by constituting a novel squalene-derived ambrein biosynthetic pathway in E. coli.
      RESULTS: The ScERG9 gene encoding the squalene synthase (SS) was integrated into
      the E. coli genome to generate a squalene-producing strain that supplied the
      central precursor squalene for the formation of cyclic triterpenoids. The mutated
      squalene-hopene synthase (D377C SHC) and the tetraprenyl-beta-curcumene cyclase
      (BmeTC) were co-expressed with SS to construct a novel ambrein biosynthetic
      pathway in E. coli. Ambrein was produced at 2.6 mg l-1. CONCLUSIONS: An E. coli
      chassis for ambrein production was constructed by combining the squalene
      synthesis module with the downstream cyclization module.

PMID- 29204768
TI  - Erratum to: Thermostability enhancement of chitosanase CsnA by fusion a family 5
      carbohydrate-binding module.
AB  - In Table 1 as published, some of the data were wrong. The corrected Table 1 is
      shown here. In addition, according to the corrected Table 1, the sentence "the k
      cat /K m of CsnA-CBM5 was higher than that of WT by 143%" in the part of "The
      kinetic parameters and specific activity" in the Results part should be changed
      to "the k cat /K m of CsnA-CBM5 was higher than that of WT by 110%".

PMID- 29204769
TI  - RNA binding protein Lin28A promotes osteocarcinoma cells progression by
      associating with the long noncoding RNA MALAT1.
AB  - OBJECTIVES: To explore the effects of Lin28A on progression of osteocarcinoma
      (OS) cells. RESULTS: Lin28A mRNA and protein expressions were significantly
      increased in OS tissues compared with that in normal adjacent tissues.
      Expressions of Lin28A and long noncoding RNA MALAT1 were positively correlated.
      Patients with higher Lin28A expression had shorter overall survival. Moreover,
      Lin28A knockdown inhibited OS cells proliferation, migration, invasion and
      promoted cell apoptosis; Lin28A was found to harbor binding sites on MALAT1
      sequences and associated with MALAT1, and increased MALAT1 stability and
      expression. Notably, the inhibition of Lin28A knockdown was attenuated or even
      reversed by MALAT1 overexpression. CONCLUSIONS: RNA binding protein Lin28A could
      facilitate OS cells progression by associating with the long noncoding RNA
      MALAT1.

PMID- 29204770
TI  - Species of family Promicromonosporaceae and family Cellulomonadeceae that produce
      cellulosome-like multiprotein complexes.
AB  - OBJECTIVES: To screen the phylogenetically-nearest members of Cellulosimicrobium
      cellulans for the production of cellulosome-like multienzyme complexes and
      extracellular beta-xylosidase activity against 7-xylosyltaxanes and to get
      corresponding molecular insights. RESULTS: Cellulosimicrobium (family
      Promicromonosporaceae) and all genera of the family Cellulomonadeceaec produced
      both cellulosome-like multienzyme complexes and extracellular beta-xylosidase
      activity, while the other genera of the family Promicromonosporaceae did not.
      Multiple sequence alignments further indicated that hypothetic protein M768_06655
      might be a possible key subunit. CONCLUSION: This is the first report that many
      actinobacteria species can produce cellulosome-like multienzyme complexes. The
      production of cellulosome-like complexes and the extracellular beta-xylosidase
      activity against 7-xylosyltaxanes might be used to differentiate the genus
      Cellulosimicrobium from other genera of the family Promicromonosporaceae.

PMID- 29204771
TI  - Comparison of blood pressure monitoring by applanation tonometry and invasively
      assessed blood pressure in cardiological patients.
AB  - The aim of this study was to evaluate the accuracy and precision of non-invasive
      continuous blood pressure measurement by applanation tonometry (AT) in awake or
      anaesthetised cardiological intensive care patients. Patients suffering from
      highly impaired left ventricular function atrial fibrillation or severe aortic
      valve stenosis were included into the study. Arterial blood pressure was recorded
      by applanation tonometry (T-Line 400, Tensys Medical(r), USA) and an arterial
      line in awake or anaesthetised patients. Discrepancies in mean (MAP), systolic
      (SAP), and diastolic (DAP) arterial pressure between the two methods were
      assessed as bias, limits of agreement and percentage error respectively. In 31
      patients a total of 27,900 measurements were analyzed. The concordance
      correlation coefficient was 0.23, 0.45 and 0.06 for MAP, SAP and DAP,
      respectively. For all patients bias for MAPAT compared to MAPAL was 14.96 mmHg
      (SAPAT 4.51 mmHg; DAPAT 19.12 mmHg) with limits of agreement for MAPAT of 46.25
      and - 16.33 mm Hg (SAPAT 48.00 and - 38.98 mmHg; DAPAT 50.12 and - 11.89 mmHg).
      Percentage error for MAPAT was 56.8% (42.7% for SAPAT; 75.2% for DAPAT). We
      conclude that the AT method is not reliable in ICU patients with severe cardiac
      comorbidities.

PMID- 29204772
TI  - A stochastic tabu search algorithm to align physician schedule with patient flow.
AB  - In this study, we consider the pretreatment phase for cancer patients. This is
      defined as the period between the referral to a cancer center and the
      confirmation of the treatment plan. Physicians have been identified as
      bottlenecks in this process, and the goal is to determine a weekly cyclic
      schedule that improves the patient flow and shortens the pretreatment duration.
      High uncertainty is associated with the arrival day, profile and type of cancer
      of each patient. We also include physician satisfaction in the objective
      function. We present a MIP model for the problem and develop a tabu search
      algorithm, considering both deterministic and stochastic cases. Experiments show
      that our method compares very well to CPLEX under deterministic conditions. We
      describe the stochastic approach in detail and present a real application.

PMID- 29204773
TI  - Circumstances and causes of sudden circulatory arrests in the Dutch province of
      Limburg and the involvement of citizen rescuers.
AB  - BACKGROUND: Recently we showed that a citizen volunteer system using text message
      alerts improves survival of out-of-hospital sudden circulatory arrest (OHCA). It
      is important to characterise the OHCA population encountered by the volunteers
      regarding circumstances and causes of the arrests. METHODS AND RESULTS: Eligible
      for this study were 968 OHCAs that occurred between April 2012 and April 2014 in
      the Dutch province of Limburg. The distribution of causes of OHCA, patient
      characteristics and resuscitation settings were compared between 492 arrests
      wherein volunteers were notified and 476 arrests where the dispatcher decided not
      to do so. In case of notification, the cause of OHCA was known in 345 cases and
      of cardiac origin (treatable) in 83.2% (287/345). About 41% of the cardiac
      arrests were caused by acute or chronic coronary artery disease. OHCA occurred
      within the home environment in about 84%. The OHCA was witnessed in 75% of the
      cases. In 60.9% of the cases a witness or bystander had already started basic
      life support. However, in approximately 18% of the OHCAs the volunteer was the
      first to start basic life support before arrival of the ambulance. In about 75%
      of the OHCAs the ambulance arrived at 6 minutes or later after time of
      notification by the dispatch centre. CONCLUSION: The volunteer system is
      predominantly activated in situations for which it was developed; cases with
      cardiac aetiology (58%) and cases in the home environment (84%). The majority of
      patients encountered by the volunteers had 'hearts too good to die', underscoring
      the benefit of deploying citizen rescuers in programs to improve survival of
      OHCA.

PMID- 29204774
TI  - Percutaneous closure of a patent foramen ovale after cryptogenic stroke.
AB  - A patent foramen ovale is a common intracardiac finding that is located between
      the left and right atrium. It can cause right-to-left shunting and has a high
      prevalence in patients who suffer a cryptogenic stroke. Earlier trials did not
      show superiority of percutaneous patent foramen ovale closure with standard
      medical therapy over standard medical therapy alone in the treatment of
      cryptogenic stroke. Interestingly, several meta-analyses show positive results
      regarding closure, suggesting underpowering of the individual trials. Recently,
      two large prospective trials and one long-term follow-up study showed benefit of
      percutaneous closure over standard medical therapy in treatment of cryptogenic
      stroke. A larger right-to-left shunt or the presence of an atrial septal aneurysm
      were predictors for a recurrent event. Therefore, percutaneous patent foramen
      ovale closure after cryptogenic stroke should be recommended over antiplatelet
      therapy alone in patients younger than 55 years of age with a high-risk patent
      foramen ovale.

PMID- 29204775
TI  - Use of a Purse-String Suture to Reduce Skin Graft Requirements.
AB  - BACKGROUND: When a wound cannot be closed in a linear fashion and either a local
      flap or skin graft is needed, a purse-string suture can be a useful adjunct to
      wound closure. Local tissue architecture is maintained in cases where clear
      surgical margins have not been achieved at the time of extirpative skin cancer
      surgery. We hypothesized that this technique could be applied to a range of wound
      sizes and locations to avoid or reduce the need for skin grafting. METHODS: We
      applied a non-absorbable purse-string suture to wounds in 18 patients over a 15
      month period and measured the defect size before and after application of the
      suture intraoperatively. Residual defects were covered with full- or split
      thickness skin grafts. Postoperative wound area, scar hypertrophy, partial graft
      loss and dehiscence following suture removal were additional outcomes. RESULTS:
      Ten patients achieved primary wound closure with the purse-string suture, while
      additional skin grafting was required in eight patients. Wounds closed primarily
      did not re-expand. Skin-grafted subjects had a 53.8% intraoperative wound area
      reduction but the skin grafts expanded during recovery, and ultimate reduction
      diminished to 11% on late follow-up. Wounds accounting for this late re-expansion
      were located on the extremities. CONCLUSIONS: Purse-string sutures are helpful
      for wound closure in wounds that cannot be closed primarily. They can decrease
      the size of a skin graft if the wound cannot be closed completely. Wound re
      expansion, particularly in extremity defects, may occur following early removal
      of the tension-bearing purse string.

PMID- 29204776
TI  - Implications of Hyperthermic Intraperitoneal Chemotherapy Perfusion-Related
      Hyperglycemia.
AB  - BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) administration can
      be associated with hyperglycemia during perfusion. Little is known about this
      effect, and no previous studies have examined patient characteristics associated
      with perfusion-related hyperglycemia. METHODS: We retrospectively identified
      consecutive patients at a single institution treated with HIPEC from 8/2003 to
      10/2016 who had intraoperative blood glucose measured. Hypertonic 1.5% dextrose
      containing peritoneal dialysate was used as carrier solution in all patients.
      Comparisons were made using parametric [Student's t test, analysis of variance
      (ANOVA)], and nonparametric tests (chi 2, Kruskal-Wallis) where appropriate.
      RESULTS: There were 85 patients identified, with average age of 53 +/- 12 years,
      69 (81%) with appendiceal or colorectal peritoneal cancer. Most patients were
      perfused with mitomycin C (69%) or oxaliplatin (24%). Intraoperative
      hyperglycemia (> 180 mg/dL) affected the majority of patients (86%), with values
      up to 651 mg/dL. Insulin was required for treatment in 66% of patients. Peak
      hyperglycemia occurred within an hour of perfusion in 91%, and resolved by
      postoperative day one in 91% of patients. Glucose > 309 mg/dL (highest quartile)
      was associated with longer operating time (p = 0.03) and with use of oxaliplatin
      compared with mitomycin C (p = 0.01). No association was found with other
      comorbidities, peritoneal carcinomatosis index score, or postoperative outcomes.
      CONCLUSIONS: Most patients experience hyperglycemia during HIPEC. This is not
      clearly associated with patient factors, and may be due to use of dextrose
      containing carrier solution. Since perioperative hyperglycemia has potential
      negative impact, use of dextrose-containing carrier solution should be questioned
      and is worth investigating further.

PMID- 29204777
TI  - Correction to: Consistent Condom Use by Female Sex Workers in Kolkata, India:
      Testing Theories of Economic Insecurity, Behavior Change, Life Course
      Vulnerability and Empowerment.
AB  - The original version of this article unfortunately contained an error. The
      authors would like to correct the error with this erratum.

PMID- 29204778
TI  - Conversion of Laparoscopic Adjustable Gastric Banding to Gastric Bypass: a
      Comparison to Primary Gastric Bypass.
AB  - INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) has a considerable
      failure rate. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the rescue
      options. This study aims to compare the complication rates and outcomes between
      LAGB converted to LRYGB and primary LRYGB. MATERIALS AND METHODS: A retrospective
      analysis was performed in all patients converted from LAGB to LRYGB between
      January 2007 and March 2017. This group was compared to a matched cohort of
      primary LRYGB patients operated during the same period. Early and late
      complications, weight loss, and improvement of comorbidities were analyzed.
      RESULTS: One hundred sixty-one revisional LRYGB patients were compared to a
      similar number of primary LRYGB patients. Preoperative age, gender distribution,
      weight, and BMI were comparable. Mean operative time was longer in the revisional
      group (137.7 vs. 112.7 min, respectively, P < 0.001). The overall early
      complication rates were comparable between the groups (7.5 vs. 11.8%, P = 0.16),
      including postoperative leak rate (0.62%). Follow-up of at least 6 months was
      attained in 78% of the patients. Revisional cases demonstrated less weight loss
      (61.5 vs. 73.5%EWL, respectively, P = 0.004) and slightly less improvement of
      comorbidities (75.0 vs. 85.7%, respectively, P = 0.09). The late complication
      rate was comparable (8.1 vs. 8.1%, P = 1.0). CONCLUSION: Albeit longer operating
      time, revision of LAGB to LRYGB is a safe procedure, with similar complication
      rates when compared to primary LRYGB. Although revisional LRYGB does result in
      less weight loss than primary LRYGB, the procedure's safety makes it a very
      plausible option as a rescue operation for failed LAGB.

PMID- 29204779
TI  - Resolution of Symptomatic Obstructive Sleep Apnea Not Impacted by Preoperative
      Body Mass Index, Choice of Operation Between Sleeve Gastrectomy and Roux-en-Y
      Gastric Bypass Surgery, or Severity.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a serious obesity-associated
      disorder that causes significant short- and long-term medical consequences.
      OBJECTIVE: The objective of this study is to compare the 6-month and 1-year
      postoperative symptomatic OSA remission rates of patients undergoing bariatric
      surgery based on their preoperative body mass index (BMI) stratification, type of
      bariatric operation-sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)
      and OSA severity. METHODS: We retrospectively analyzed 297 obese patients with a
      diagnosis of OSA who had undergone either SG or RYGB between 2011 and 2015.
      RESULTS: The overall 6-month symptomatic OSA remission rate for patients (n =
      255) was 74.5%. At 6 months, patients with a preoperative BMI of 30-34.9 kg/m2
      (class I), 35-39.9 kg/m2 (class II), and 40+ kg/m2 (class III) had 100, 70.0, and
      75.0% (p = 0.2164) remission rates, respectively. The 6-month remission rates for
      SG and RYGB were 75.3 and 70.8% (p = 0.5165), respectively. The overall 1-year
      symptomatic OSA remission rate for patients (n = 162) was 87.1%. At 1 year, class
      I, II, and III patients had 100, 85.7, and 87.5% (p = 0.5740) remission rates,
      respectively. The 1-year remission rates for SG and RYGB were 89.2 and 81.2% (p =
      0.2189), respectively. A sub-analysis (n = 69) based on preoperative OSA severity
      levels did not affect the remission outcome at either the 6-month (p = 0.3670) or
      1-year (p = 0.3004) follow-up. CONCLUSION: Most obese patients experience
      symptomatic remission of their OSA after bariatric surgery, regardless of their
      preoperative BMI, choice of operation, or OSA severity.

PMID- 29204781
TI  - Fungal Communities and Functional Guilds Shift Along an Elevational Gradient in
      the Southern Appalachian Mountains.
AB  - Nitrogen deposition alters forest ecosystems particularly in high elevation,
      montane habitats where nitrogen deposition is greatest and continues to increase.
      We collected soils across an elevational (788-1940 m) gradient, encompassing both
      abiotic (soil chemistry) and biotic (vegetation community) gradients, at eight
      locations in the southern Appalachian Mountains of southwestern North Carolina
      and eastern Tennessee. We measured soil chemistry (total N, C, extractable PO4,
      soil pH, cation exchange capacity [ECEC], percent base saturation [% BS]) and
      dissected soil fungal communities using ITS2 metabarcode Illumina MiSeq
      sequencing. Total soil N, C, PO4, % BS, and pH increased with elevation and
      plateaued at approximately 1400 m, whereas ECEC linearly increased and C/N
      decreased with elevation. Fungal communities differed among locations and were
      correlated with all chemical variables, except PO4, whereas OTU richness
      increased with total N. Several ecological guilds (i.e., ectomycorrhizae,
      saprotrophs, plant pathogens) differed in abundance among locations;
      specifically, saprotroph abundance, primarily attributable to genus Mortierella,
      was positively correlated with elevation. Ectomycorrhizae declined with total N
      and soil pH and increased with total C and PO4 where plant pathogens increased
      with total N and decreased with total C. Our results demonstrate significant
      turnover in taxonomic and functional fungal groups across elevational gradients
      which facilitate future predictions on forest ecosystem change in the southern
      Appalachians as nitrogen deposition rates increase and regional temperature and
      precipitation regimes shift.

PMID- 29204780
TI  - Silver oxide nanoparticles alleviate indomethacin-induced gastric injury: a novel
      antiulcer agent.
AB  - Silver and silver oxides are gaining interest in medical applications for their
      prominent antibacterial and antimicrobial potentials. Recent studies suggest that
      nanosilver oxide has remarkable anti-inflammatory effects and enhances wound
      healing. Nevertheless, its effect on gastric ulcer has not yet been illustrated.
      Thus the current study aimed to explore the prospect protective effect of
      nanosilver oxide against indomethacin-induced gastric ulcer. A new approach has
      been followed to synthesize nanosilver oxide. X-ray diffraction, UV-Vis
      spectroscopy and transition electron microscope techniques have been successfully
      used to characterize the synthesized nanoparticles. Treatment of ulcerated rats
      with different doses of nanosilver oxide especially (175 and 350 ppm/p.o.)
      alleviated adverse effects of indomethacin-induced gastric injury as demonstrated
      by decreasing ulcer index and elevating % of ulcer inhibition. These positive
      effects excelled those exerted by the reference antiulcer drug omeprazole.
      Nanosilver oxide suppressed gastric inflammation by reducing myeloperoxidase,
      tumor necrosis alpha, interleukin 1beta and interferon gamma. Moreover,
      nanosilver oxide halted gastric oxidative stress via inhibiting lipid 
      peroxidation and enhancing glutathione and paraoxonase-1. Regarding gastric
      apoptosis, nanosilver oxide down regulated the expression of caspase 9, tumor
      protein 53, and nuclear factor kappa B and allograft inflammatory factor-1 genes.
      These findings emphasize the antiulcerogenic potential of nanosilver oxide
      against indomethacin-induced gastric ulcers which are multi-factorial including
      anti-inflammatory, antioxidant and antiapoptotic effects.

PMID- 29204782
TI  - Adjusting for cross-cultural differences in computer-adaptive tests of quality of
      life.
AB  - PURPOSE: Previous studies using the WHOQOL measures have demonstrated that the
      relationship between individual items and the underlying quality of life (QoL)
      construct may differ between cultures. If unaccounted for, these differing
      relationships can lead to measurement bias which, in turn, can undermine the
      reliability of results. METHODS: We used item response theory (IRT) to assess
      differential item functioning (DIF) in WHOQOL data from diverse language versions
      collected in UK, Zimbabwe, Russia, and India (total N = 1332). Data were fitted
      to the partial credit 'Rasch' model. We used four item banks previously derived
      from the WHOQOL-100 measure, which provided excellent measurement for physical,
      psychological, social, and environmental quality of life domains (40 items
      overall). Cross-cultural differential item functioning was assessed using
      analysis of variance for item residuals and post hoc Tukey tests. Simulated
      computer-adaptive tests (CATs) were conducted to assess the efficiency and
      precision of the four items banks. RESULTS: Splitting item parameters by DIF
      results in four linked item banks without DIF or other breaches of IRT model
      assumptions. Simulated CATs were more precise and efficient than longer paper
      based alternatives. DISCUSSION: Assessing differential item functioning using
      item response theory can identify measurement invariance between cultures which,
      if uncontrolled, may undermine accurate comparisons in computer-adaptive testing
      assessments of QoL. We demonstrate how compensating for DIF using item anchoring
      allowed data from all four countries to be compared on a common metric, thus
      facilitating assessments which were both sensitive to cultural nuance and
      comparable between countries.

PMID- 29204783
TI  - The impact of rehabilitative interventions on quality of life: a qualitative
      evidence synthesis of personal experiences of individuals with amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: The nature of amyotrophic lateral sclerosis (ALS) is progressive and
      degenerative, thus influencing individuals physically, emotionally, and socially.
      A broad review of qualitative studies that describe the personal experiences of
      people with ALS with physiotherapy, occupational therapy and speech and language
      pathology interventions, and how those affect QoL is warranted. PURPOSE: This
      study synthesizes qualitative research regarding the potential that
      rehabilitation interventions have to maintain and/or improve QoL from the
      perspective of people with ALS. METHODS: The SPIDER search strategy was applied
      and five articles met inclusion criteria addressing the perceived impact of
      rehabilitation on QoL for individuals with ALS. RESULTS: Four themes emerged: the
      concept of control; adapting interventions to disease stage; struggles with
      interventions; and barriers between healthcare providers and patients.
      CONCLUSIONS: Rehabilitation interventions were perceived to have potential to
      support QoL by people with ALS. Advantages and limitations of rehabilitation
      services within this population were identified.

PMID- 29204784
TI  - Long-term quality of life changes after primary septorhinoplasty.
AB  - PURPOSE: Health-related quality of life measurements are gaining in importance in
      clinical medicine. Little is known about the long-term quality of life changes
      after septorhinoplasty. This study was designed to analyse the long-term quality
      of life impacts of septorhinoplasty, using disease-specific instruments
      rhinoplasty outcome evaluation (ROE) and Functional Rhinoplasty Outcome Inventory
      17 (FROI-17); as well as a generic instrument-Short-Form 36 Health Survey (SF
      36). METHODS: Patients completed the FROI-17, the ROE and the SF-36
      preoperatively and at 12 and 60 months postoperatively. General demographic and
      clinical information (age, gender, allergies, medication, medical and surgical
      history) were collected from all patients. RESULTS: We report a significant
      increase in disease-specific QOL after primary septorhinoplasty (as measured with
      the ROE & FROI-17) and in two scales of the SF-36 generic instrument (role
      functioning physical and mental health) 1 year after surgery. Our patients showed
      further significant increase in disease-specific QOL (FROI-17) after their
      primary septorhinoplasty (1 year vs. 5 years postoperatively). SF-36 results
      showed significant improvements 5 years postoperatively (compared to preoperative
      scores) in six out of eight scales (physical functioning, role-functioning
      physical, bodily pain, vitality, social functioning and mental health).
      CONCLUSION: Septorhinoplasty can improve disease-specific and non-disease
      specific QOL in the short- and long-term postoperative period. These improvements
      remain measurable 5 years after surgery.

PMID- 29204786
TI  - The Influence of Comprehensive Cardiac Rehabilitation on Heart Rate Variability
      Indices after CABG is More Effective than after PCI.
AB  - The aim of this study was to evaluate the influence of cardiac rehabilitation
      (CR) on heart rate variability (HRV) indices in men with coronary artery disease
      (CAD) treated with percutaneous coronary intervention (PCI) or coronary artery
      bypass graft surgery (CABG). The study population consisted of 131 male patients
      with CAD prospectively and consecutively admitted to CR after PCI n = 72, or CABG
      n = 59. Participants performed cycle ergometer interval training for 45 min three
      times a week for 8 weeks. At baseline and after 8 weeks, all patients underwent
      the HRV assessment. HRV indices in CAGB survivals were significantly lower in
      comparison to PCI patients at baseline. Significant increases were seen for SDNN,
      rMSSD, and HF in the CABG group and only in HF component in PCI group after 8
      weeks of CR. Eight weeks of CR seems to be more effective in CABG patients than
      patients after PCI.

PMID- 29204785
TI  - Quality of life of French Canadian parents raising a child with autism spectrum
      disorder and effects of psychosocial factors.
AB  - PURPOSE: This study aimed to investigate the quality of life of parents of a
      child with autism spectrum disorder in Quebec. METHODS: Seventy-seven
      participants completed a questionnaire with socio-biographic information and five
      self-assessed scales, to measure perceived stress, social support and control,
      coping strategies, and quality of life. RESULTS: Perception of their child's
      autonomy level, of the severity of the disorder, of the family's income, as well
      as changes in their professional or familial organization influenced parents'
      quality of life. Perceiving their situation as a threat predicted poor quality of
      life, whereas satisfaction of social support predicted good quality of life. In
      addition, parents who used problem solving and support-seeking coping strategies
      had a better relationship with their child, whereas those who used more emotion
      centered coping strategies struggled. Lastly, parents who felt they had the power
      to contribute to their child's development were more satisfied and less
      disturbed. CONCLUSIONS: Beyond the parents' actual situation, our results
      underscore the importance of paying attention to their own perception of the
      situation in order to provide them with appropriate support.

PMID- 29204788
TI  - Modeling Drug Disposition and Drug-Drug Interactions Through Hypothesis-Driven
      Physiologically Based Pharmacokinetics: a Reversal Translation Perspective.

PMID- 29204787
TI  - The complete genome sequence of a third distinct baculovirus isolated from the
      true armyworm, Mythimna unipuncta, contains two copies of the lef-7 gene.
AB  - A baculovirus isolate from a USDA Forest Service collection was characterized by
      electron microscopy and analysis of its genome sequence. The isolate, formerly
      referred to as Pseudoletia (Mythimna) sp. nucleopolyhedrovirus #7 (MyspNPV#7),
      was determined by barcoding PCR to derive from the host species Mythimna
      unipuncta (true armyworm) and was renamed Mythimna unipuncta nucleopolyhedrovirus
      #7 (MyunNPV#7). The occlusion bodies (OBs) and virions exhibited a size and
      morphology typical for OBs produced by the species of genus Alphabaculovirus,
      with occlusion-derived virions consisting of 2-5 nucleocapsids within a single
      envelope. The MyunNPV#7 genome was determined to be 148,482 bp with a 48.58% G+C
      nucleotide distribution. A total of 159 ORFs of 150 bp or larger were annotated
      in the genome sequence, including the 38 core genes of family Baculoviridae. The
      genome contained six homologous repeat regions (hrs) consisting of multiple
      copies of a 34-bp imperfect palindrome. Phylogenetic inference from concatenated
      baculovirus core gene amino acid sequence alignments placed MyunNPV#7 with group
      II alphabaculoviruses isolated from other armyworm and cutworm host species of
      lepidopteran family Noctuidae. MyunNPV#7 could be distinguished from other
      viruses in this group on the basis of differences in gene content and order.
      Pairwise nucleotide distances suggested that MyunNPV#7 represents a distinct
      species in Alphabaculovirus. The MyunNPV#7 genome was found to contain two copies
      of the late expression factor-7 (lef-7) gene, a feature not reported for any
      other baculovirus genome to date. Both copies of lef-7 encoded an F-box domain,
      which is required for the function of LEF-7 in baculovirus DNA replication.

PMID- 29204789
TI  - A Preliminary Study on Precision Image Guidance for Electrode Placement in an EEG
      Study.
AB  - Conventional methods for positioning electroencephalography electrodes according
      to the international 10/20 system are based on the manual identification of the
      principal 10/20 landmarks via visual inspection and palpation, inducing
      intersession variations in their determined locations due to structural ambiguity
      or poor visibility. To address the variation issue, we propose an image guidance
      system for precision electrode placement. Following the electrode placement
      according to the 10/20 system, affixed electrodes are laser-scanned together with
      the facial surface. For subsequent procedures, the laser scan is conducted
      likewise after positioning the electrodes in an arbitrary manner, and following
      the measurement of fiducial electrode locations, frame matching is performed to
      determine a transformation from the coordinate frame of the position tracker to
      that of the laser-scanned image. Finally, by registering the intra-procedural
      scan of the facial surface to the reference scan, the current tracking data of
      the electrodes can be visualized relative to the reference goal positions without
      manually measuring the four principal landmarks for each trial. The experimental
      results confirmed that use of the electrode navigation system significantly
      improved the electrode placement precision compared to the conventional 10/20
      system (p < 0.005). The proposed system showed the possibility of precise image
      guided electrode placement as an alternative to the conventional manual 10/20
      system.

PMID- 29204791
TI  - Correction to: Taxonomic resolution and functional traits in the analysis of
      tropical oribatid mite assemblages.
AB  - Due to an unfortunate turn of events, the statistical results for TS1 (F- and p
      values) in Table 4 were displayed in reversed order. The correct representation
      of Table 4 is published here and should be treated as definitive.

PMID- 29204790
TI  - Cytoplasmic expression of Twist1, an EMT-related transcription factor, is
      associated with higher grades renal cell carcinomas and worse progression-free
      survival in clear cell renal cell carcinoma.
AB  - Twist1 is a key transcription factor, which confers tumor cells with cancer stem
      cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in
      pathological conditions including tumor malignancy and metastasis. This study
      aimed to evaluate the expression patterns and clinical significance of Twist1 in
      renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were
      examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear
      cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas
      (pRCC) and 34 (13.5%) chromophobe renal cell carcinoma, by immunohistochemistry
      on a tissue microarray. The association between expression of this marker and
      clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was
      mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic
      expression of Twist1 was associated with higher grade tumors (P = 0.045), renal
      vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was
      positively correlated with higher grade tumors (P = 0.026), shorter progression
      free survival time (P = 0.027) in patients with ccRCC, and also with higher stage
      in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels
      of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive
      tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in
      worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than
      nuclear expression of Twist1 can be considered as a prognostic and therapeutic
      marker for targeted therapy of RCC, especially for ccRCC patients.

PMID- 29204793
TI  - The Quantificational Domain of dou: An Experimental Study.
AB  - Which NP does all associate with in e.g. "The pandas, the children all saw"-the
      pandas, the children, or both? The intuition of adult Mandarin Chinese native
      speakers regarding the interpretation of the adverbial quantifier dou 'all'
      remains unclear and controversial, and various incommensurate theories of domain
      selection have been proposed. These studies may have failed to yield clear
      results because they used testing materials in which the interpretation of dou is
      confounded with other principles of NP interpretation (e.g. zhexie xiaohai 'these
      children' is truth-functionally synonymous with 'all these children'). To address
      these concerns, we present the first set of experimental studies on adult
      knowledge and use of syntactic constraints on the quantifier domain of dou. The
      results support the hypothesis that dou can take one and only one c-commanding NP
      as its domain, but falsify interesting theoretical accounts that assume a strict
      locality constraint on dou quantification.

PMID- 29204794
TI  - Thoracic aortic aneurysm: unlocking the "silent killer" secrets.
AB  - Thoracic aortic aneurysm (TAA) is an increasingly recognized condition that is
      often diagnosed incidentally. This review discusses ten of the most relevant
      epidemiological and clinical secrets of this disease; (1) the difference in
      pathogenesis between ascending and descending TAAs. TAAs at these two sites act
      as different diseases, which is related to the different embryologic origins of
      the ascending and descending aorta. (2) The familial pattern and genetics of
      thoracic aneurysms. Syndromic TAAs only explain 5% of the pattern of inheritance.
      (3) The effect of female sex on TAA growth and outcome. Females have been found
      to have worse outcomes compared to males. (4) Guilt by Association. TAAs are
      associated with abdominal aortic aneurysms, intracranial aneurysms, bicuspid
      aortic valve, and inflammatory disorders. (5) Natural history of TAAs. Important
      findings have been made regarding the expansion rate (in relation to familial
      pattern, location and size), and also regarding the risk of rupture or
      dissection. (6) The aortic size paradox. Size only is not a sufficient predictor
      of risk of dissection. (7) Biomarker void. Although many serum biomarkers have
      been studied, imaging remains the only reliable method for diagnosis and follow
      up. (8) Indications for repair. Decisions are made depending on symptoms,
      location, size, and familial patterns. (9) Types of repair. Both open and
      endovascular repair options are available for certain TAAs. (10) Medical
      treatment. The efficacy of prescribing beta blockers, angiotensin converting
      enzyme inhibitors or angiotensin receptor blockers remains dubious.

PMID- 29204792
TI  - Possible Balancing Selection in Human Female Homosexuality.
AB  - A growing number of researchers suggest that female homosexuality is at least in
      part influenced by genetic factors. Unlike for male homosexuality, few familial
      studies have attempted to explore maintenance of this apparently fitness
      detrimental trait in the population. Using multiple recruitment methods, we
      explored fecundity and sexual orientation within the pedigrees of 1,458 adult
      female respondents. We compared 487 homosexual and 163 bisexual with 808
      heterosexual females and 30,203 of their relatives. Our data suggest that the
      direct fitness of homosexual females is four times lower than the direct fitness
      of heterosexual females of corresponding ages. The prevalence of
      nonheterosexuality within the homosexual female respondents' families (2.83%)
      appear to be more than four times higher than the basal prevalence in the Italian
      population (0.63%). Pedigree size and relative fecundity in both the paternal and
      maternal sides of the homosexual women's families were significantly higher than
      in the heterosexuals' families. If confirmed, the relative average fecundity
      increase within the family seems to offset the loss in fitness due to the low
      direct fitness of homosexual females. Therefore, the balanced fecundity in the
      homosexual females' families may allow the trait to be maintained at a low
      frequency equilibrium in the population.

PMID- 29204795
TI  - Inferring Gene Regulatory Networks Based on a Hybrid Parallel Genetic Algorithm
      and the Threshold Restriction Method.
AB  - Inferring gene regulatory networks (GRNs) is a challenging computational task in
      system biology. Many inference algorithms have been proposed along with related
      modifications to various problems. Every algorithm has its own advantages and
      drawbacks. In particular, the efficiency of each algorithm is not as good as
      people expect. A novel inference algorithm is proposed in this paper that can be
      divided into two parts. In the first part, the pre-computational part, two tasks
      must be accomplished: singular value decomposition for solution space
      determination and the threshold restriction method for redundant edge deletion.
      The second part of the algorithm is a hybrid parallel genetic algorithm. In this
      part, a parallel genetic algorithm is used for a first quick search, after which
      hill climbing is used for an exact search. The proposed algorithm is validated on
      both melanoma and type II diabetes GRNs and is compared with other algorithms.
      The efficiency of our algorithm was tested with different numbers of echoes and
      nodes. The cross-validation results confirmed the effectiveness of our algorithm,
      which significantly outperforms other algorithms.

PMID- 29204797
TI  - Prevention of Renal Scarring in Acute Pyelonephritis by Probiotic Therapy: an
      Experimental Study.
AB  - We evaluated the protective effects of probiotic administration as a prophylaxis
      treatment and immediately after fever onset in increasing the immune response and
      decreasing the renal scarring in a rat model of acute pyelonephritis. Twenty-four
      rats were apportioned to three groups. In GI (n = 8), the rats were injected with
      direct inoculation of Escherichia coli into the right kidney. In GII (n = 8), the
      rats received a probiotic regimen 1 month before E. coli injection and the
      probiotic regimen was continued for the next 2 months. In GIII (n = 8), the
      probiotic regimen was started just after E. coli injection and was continued for
      2 months. Technetium-99m-DMSA renal scan, histopathological evaluations,
      concentrations of CA19-9, IgA, blood urea nitrogen (BUN), and creatinine were
      assessed 1 and 2 months post-injection. It took an average of 4.2 +/- 1.1 h
      between the injection and onset of fever in GI and GII. In GIII, this period was
      longer (7.5 +/- 1.4). Probiotic administration resulted in reduction of
      interstitial fibrosis and tubular and glomerular atrophy in GII in all follow
      ups. Technetium-99m-DMSA renal scan showed that the right kidney reached near the
      normal cortical integrity (47%) in GII compared to GI (32%) after 2 months of
      injection. However, the renal integrity did not improve significantly in GIII
      (41%). In GII, CA19-9 was lower (p < 0.05), while the levels of serum and fecal
      IgA were higher (p < 0.05). Administration of the probiotic regimen in the rat
      model may decrease renal damage in pyelonephritis. In spite of better results in
      the prophylactic group compared to the treatment group, no strong evidence was
      found to prove the advantage of its prophylactic application over the treatment
      administration.

PMID- 29204796
TI  - Identifying Effective Components of Child Maltreatment Interventions: A Meta
      analysis.
AB  - There is a lack of knowledge about specific components that make interventions
      effective in preventing or reducing child maltreatment. The aim of the present
      meta-analysis was to increase this knowledge by summarizing findings on effects
      of interventions for child maltreatment and by examining potential moderators of
      this effect, such as intervention components and study characteristics.
      Identifying effective components is essential for developing or improving child
      maltreatment interventions. A literature search yielded 121 independent studies
      (N = 39,044) examining the effects of interventions for preventing or reducing
      child maltreatment. From these studies, 352 effect sizes were extracted. The
      overall effect size was significant and small in magnitude for both preventive
      interventions (d = 0.26, p < .001) and curative interventions (d = 0.36, p <
      .001). Cognitive behavioral therapy, home visitation, parent training, family
      based/multisystemic, substance abuse, and combined interventions were effective
      in preventing and/or reducing child maltreatment. For preventive interventions,
      larger effect sizes were found for short-term interventions (0-6 months),
      interventions focusing on increasing self-confidence of parents, and
      interventions delivered by professionals only. Further, effect sizes of
      preventive interventions increased as follow-up duration increased, which may
      indicate a sleeper effect of preventive interventions. For curative
      interventions, larger effect sizes were found for interventions focusing on
      improving parenting skills and interventions providing social and/or emotional
      support. Interventions can be effective in preventing or reducing child
      maltreatment. Theoretical and practical implications are discussed.

PMID- 29204799
TI  - Dorsomedial prefrontal cortex 5-HT6 receptors regulate anxiety-like behavior.
AB  - The dorsomedial prefrontal cortex (dmPFC) plays a very important role in decision
      related and anxiety-related information processing. It has enriched 5-HT6
      receptors; however, the precise role of dmPFC 5-HT6 receptors in anxiety remains
      to be fully investigated. In this study, we injected dmPFC with the 5-HT6
      receptor agonist EMD 386088 and antagonist SB 271046 using stereotactic
      technology. 5-HT6 receptor activation in mice increased time spent in the center
      area on the open-field test, increased exploration of the open arms on the
      elevated plus maze test, and increased ratio on the social interaction test. 5
      HT6 receptor inactivation induced the opposite effects. In brain slices, EMD
      386088 decreased both spontaneous inhibitory postsynaptic currents (sIPSC) and
      spontaneous excitatory postsynaptic currents (sEPSC), while SB 271046 only
      increased sEPSC. These effects of EMD 386088 and SB 271046 could be reversed by
      the GABAA receptor antagonist bicuculline (BMI) and positive allosteric modulator
      clonazepam (CLZ), respectively. Our results suggest that neurotransmission in the
      dmPFC by 5-HT6 receptor activation and inhibition may play an important role in
      anxiety-like behavior, and may provide new insight into the pathological
      mechanism and potential target of anxiety disorders.

PMID- 29204798
TI  - Predicting risk decisions in a modified Balloon Analogue Risk Task: Conventional
      and single-trial ERP analyses.
AB  - Event-related potential (ERP) has the potential to reveal the temporal
      neurophysiological dynamics of risk decision-making, but this potential has not
      been fully explored in previous studies. When predicting risk decision with ERPs,
      most studies focus on between-trial analysis that reflects feedback learning,
      while within-trial analysis that could directly link option assessment with
      behavioral output has been largely ignored. Suitable task design is crucial for
      applying within-trial prediction. In this study, we used a modified version of
      the classic Balloon Analogue Risk Task (BART). In each trial of the task,
      participants made multiple rounds of decisions between a risky option (pump up
      the balloon) and a safe option (cash out). Behavioral results show that as the
      level of economic risk increased, participants were less willing to make a risky
      decision and also needed a longer response time to do so. In general, the ERP
      results showed distinct characteristics compared with previous findings based on
      between-trial prediction, particularly about the role of the P1 component.
      Specifically, both the P1 (amplitude and latency) and P3 (amplitude) components
      evoked by current outcomes predicted subsequent decisions. We suggest that these
      findings indicate the importance of selective attention (indexed by the P1) and
      motivational functions (indexed by the P3), which may help clarify the cognitive
      mechanism of risk decision-making. The theoretical significance of these findings
      is discussed.

PMID- 29204801
TI  - IMPS 2017: Business Meeting Minutes : University of Zurich, Room KO2-F-180,
      Zurich, Switzerland, July 20, 2017.

PMID- 29204800
TI  - Hospital pharmacists' perceived beliefs and responsibilities in indication-based
      off-label prescribing.
AB  - Background Off-label prescribing is prevalent in healthcare. There is a lack of
      understanding of pharmacists' attitudes toward the practice of off-label
      prescribing, especially those that are prescribed for other indications than
      approved ones (termed as indication-based off-label prescribing). Objective
      Explore hospital pharmacists' attitudes toward and perceived responsibility in
      off-label and indication-based off-label prescribing in hospital pharmacy
      practice. Setting Pharmacists practicing in hospitals in the United States were
      investigated. Method Pharmacists were contacted via email through State
      affiliates of the American Society of Health-System Pharmacist. The survey
      described an indication-based off-label medication order for a hospitalized
      patient and the prescribing physician. Data were collected via Qualtrics. Main
      outcome measure Questions focused on awareness, beliefs, and responsibility
      including, risk assessment and monitoring outcomes-related to off-label and
      indication-based offlabel prescribing. Results Of 107 pharmacist respondents,
      about 79% and 98% reported being familiar with offlabel and indication-based off
      label prescribing, respectively. While 77.6% pharmacists believed that patients
      should be informed, only 37.4% agreed that they had responsibility of informing
      physicians; presence of policy was associated (p < 0.02) with pharmacist agreeing
      to inform physicians. Over 70% agreed that patients should be closely monitored
      for outcomes and 43.1% believed physicians had predominant responsibility of
      monitoring outcomes. Conclusion Pharmacists' perceived responsibility and beliefs
      regarding off-label prescribing are insightful that can be utilized for improving
      patient care.

PMID- 29204802
TI  - Direct Schmid-Leiman Transformations and Rank-Deficient Loadings Matrices.
AB  - The Schmid-Leiman (S-L; Psychometrika 22: 53-61, 1957) transformation is a
      popular method for conducting exploratory bifactor analysis that has been used in
      hundreds of studies of individual differences variables. To perform a two-level S
      L transformation, it is generally believed that two separate factor analyses are
      required: a first-level analysis in which k obliquely rotated factors are
      extracted from an observed-variable correlation matrix, and a second-level
      analysis in which a general factor is extracted from the correlations of the
      first-level factors. In this article, I demonstrate that the S-L loadings matrix
      is necessarily rank deficient. I then show how this feature of the S-L
      transformation can be used to obtain a direct S-L solution from an unrotated
      first-level factor structure. Next, I reanalyze two examples from Mansolf and
      Reise (Multivar Behav Res 51: 698-717, 2016) to illustrate the utility of 'best
      fitting' S-L rotations when gauging the ability of hierarchical factor models to
      recover known bifactor structures. Finally, I show how to compute direct bifactor
      solutions for non-hierarchical bifactor structures. An online supplement includes
      R code to reproduce all of the analyses that are reported in the article.

PMID- 29204803
TI  - DOCK2 Deficiency in a Patient with Hyper IgM Phenotype.

PMID- 29204804
TI  - Influence of preoptic estradiol on behavioral and neural response to cocaine in
      female Sprague-Dawley rats.
AB  - RATIONALE: Systemic estradiol (E2) increases the behavioral and neural response
      to cocaine. Where in the brain E2 acts to modulate cocaine response is not
      entirely clear. Evidence supports a role in this modulation for several candidate
      regions, including the medial preoptic area (mPOA). OBJECTIVES: This study
      examined whether manipulation of E2 in the mPOA modulates differing behavioral
      responses to cocaine and whether this is reflected in differing levels of c-Fos
      in the NAc following cocaine administration. METHODS: Female rats received
      ovariectomies and bilateral cannulations of the mPOA. They then received either
      artificial cerebrospinal fluid (aCSF) or E2 microinjections into the mPOA the day
      before receiving systemic injections of saline or cocaine (5 or 10 mg/kg).
      Conditioned-place preference (CPP) to cocaine and locomotor activation were then
      obtained. RESULTS: Animals receiving 10 mg/kg, but not 5 mg/kg, cocaine developed
      significant CPP, and those receiving E2 into the mPOA expressed greater CPP than
      those receiving microinjections of only aCSF at both doses (p < 0.05, d > 0.80).
      Cocaine also caused significant psychomotor activation, but this was not
      dependent on microinjection of E2 in the mPOA. Finally, animals that received
      cocaine had increased NAc core and shell c-Fos relative to animals that received
      saline, with animals receiving both E2 microinjections and systemic cocaine
      expressing the highest activation in the caudal NAc, compared to rats receiving
      aCSF microinjections and systemic cocaine (p = 0.05, d = 0.70). CONCLUSIONS:
      These results indicate that E2 in the mPOA facilitates the behavioral response
      and neural activation that follows cocaine administration. Furthermore, they
      confirm the close relationship between the mPOA and cocaine response.

PMID- 29204806
TI  - Promotion of Healthy Humor Cancer Education Messages for the Deaf Community.
AB  - The Deaf community members of this community-campus partnership identified the
      lack of health information in American Sign Language (ASL) as a significant
      barrier to increasing the Deaf community's health knowledge. Studies have shown
      that the delivery of health messages in ASL increased Deaf study participants'
      cancer knowledge. Once health messages are available on the Internet, strategies
      are needed to attract viewers to the website and to make repeat visits in order
      to promote widespread knowledge gains. This feasibility study used the
      entertainment-education strategy of coupling cancer information with jokes in ASL
      to increase the appeal and impact of the health messages. ASL-delivered cancer
      control messages coupled with Deaf-friendly jokes were shown to 62 Deaf
      participants. Participants completed knowledge questionnaires before, immediately
      after, and 1 week after viewing the paired videos. Participants' health knowledge
      statistically significantly increased after viewing the paired videos and the
      gain was retained 1 week later. Participants also reported sharing the newly
      acquired information with others. Statistically significant results were
      demonstrated across nearly all measures, including a sustained increase in cancer
      information-seeking behavior and intent to improve health habits. Most
      participants reported that they would be motivated to return to such a website
      and refer others to it, provided that it was regularly updated with new jokes.

PMID- 29204805
TI  - The Epidemiology of Depressive Symptoms and Poor Sleep: Findings from the English
      Longitudinal Study of Ageing (ELSA).
AB  - PURPOSE: The reasons for the comorbidity between depressed mood and poor sleep
      are not well understood. METHOD: Participants were 5172 adults aged 50 years and
      older from the English Longitudinal Study of Ageing. Sleep was measured via self
      report and depressive symptoms using the Centre for Epidemiological Studies
      Depression scale. RESULTS: Greater depressive symptoms and sleep complaints were
      associated with female sex, non-cohabitation, relative poverty, smoking,
      infrequent physical activity, infrequent alcohol consumption, higher body mass
      index (BMI), diagnosis of hypertension, coronary heart disease, diabetes/high
      blood glucose, pulmonary disease, arthritis, and higher levels of fibrinogen and
      C-reactive protein (all p < 0.05). At a 4-year follow-up, depressive symptoms and
      sleep complaints were both predicted by baseline depressive symptoms and sleep
      complaints, relative poverty, smoking, physical inactivity, BMI, and arthritis
      (all p < 0.05). CONCLUSION: Depressive symptoms and sleep complaints share a
      range of correlates cross-sectionally and prospectively. These findings highlight
      the common comorbidity between depressive symptoms and sleep complaints
      underscoring the need for further research to understand their combined
      detrimental effect on long-term health and wellbeing.

PMID- 29204807
TI  - Analysis of fMRI data using noise-diffusion network models: a new covariance
      coding perspective.
AB  - Since the middle of the 1990s, studies of resting-state fMRI/BOLD data have
      explored the correlation patterns of activity across the whole brain, which is
      referred to as functional connectivity (FC). Among the many methods that have
      been developed to interpret FC, a recently proposed model-based approach
      describes the propagation of fluctuating BOLD activity within the recurrently
      connected brain network by inferring the effective connectivity (EC). In this
      model, EC quantifies the strengths of directional interactions between brain
      regions, viewed from the proxy of BOLD activity. In addition, the tuning
      procedure for the model provides estimates for the local variability (input
      variances) to explain how the observed FC is generated. Generalizing, the network
      dynamics can be studied in the context of an input-output mapping-determined by
      EC-for the second-order statistics of fluctuating nodal activities. The present
      paper focuses on the following detection paradigm: observing output covariances,
      how discriminative is the (estimated) network model with respect to various input
      covariance patterns? An application with the model fitted to experimental fMRI
      data-movie viewing versus resting state-illustrates that changes in local
      variability and changes in brain coordination go hand in hand.

PMID- 29204808
TI  - Implementing a Virtual Health Telemedicine Program in a Community Setting.
AB  - Aurora Health Care in eastern Wisconsin has a clinical genetics program driven by
      genetic counselors in the cancer/adult and prenatal genetics settings. In 2015,
      the workforce shortage of genetic counselors left us with 4 open positions for
      genetic counselors that we were unable to fill. We explored many models of
      alternative service delivery, and determined virtual health (VH) via telemedicine
      to be the best option for our system. Historically, telemedicine technologies
      have been used to provide access to healthcare services to patients in remote
      areas. We, however, were struggling to find genetics counselors to staff both our
      remote clinics and urban clinics. To solve this problem, we recruited genetic
      counselors from across the country to work remotely from their current home or
      home office utilizing VH to staff our clinics. We then created clinical workflows
      and an implementation process of virtual health for 9 prenatal and cancer clinics
      across the eastern Wisconsin footprint of our healthcare system over the course
      of 12 months. Here we provide our experience and process in establishing a VH
      program in order to help other institutions that have been affected by the
      workforce shortage of clinical genetics professionals.

PMID- 29204809
TI  - Genesurance Counseling: Genetic Counselors' Roles and Responsibilities in Regards
      to Genetic Insurance and Financial Topics.
AB  - While traditional components of genetic counseling sessions are well recognized,
      less is known about insurance and financial discussions. This study sought to
      examine "genesurance counseling" which we defined as: that portion of a genetic
      counseling session, whether intentional or non-intentional, that is devoted to
      the topic of costs and insurance/third party coverage (particularly for genetic
      testing). Our objective was to assess genetic counselors' practices and
      perspective related to genesurance counseling. A survey link was sent by e-mail
      to members of the National Society of Genetic Counselors (approximately 3100 NSGC
      members). A total of 571 genetic counselors participated in the survey of which
      550 identified as clinical genetic counselors. Survey data were used to
      investigate differences between specialties, impact on patient rapport, changes
      in practice dynamics, and devotion of clinic time. Overwhelmingly, 99% of
      participants acknowledged conducting genesurance counseling, 87% believed it to
      be part of their job description, and 85% viewed it as an important aspect of
      genetic counseling. On average, respondents estimated they devoted 10% of their
      session, or 6 min, to genesurance counseling. Of the surveyed participants, 95%
      reported genesurance counseling as having some form of influence in a patient's
      decision regarding genetic testing, and 74% stated that genesurance counseling
      concerns change the practice and dynamic of their clinic. "Genesurance
      counseling" is not a topic which has been studied to date. Our study highlights
      the changes in genetic counselors' roles and responsibilities regarding insurance
      and financial counseling.

PMID- 29204810
TI  - High-Risk Palliative Care Patients' Knowledge and Attitudes about Hereditary
      Cancer Testing and DNA Banking.
AB  - Even at the end of life, testing cancer patients for inherited susceptibility may
      provide life-saving information to their relatives. Prior research suggests
      palliative care inpatients have suboptimal understanding of genetic importance,
      and testing may be underutilized in this clinical setting. These conclusions are
      based on limited research. This study aimed to estimate genetic testing
      prevalence among high-risk palliative care patients in a National Cancer
      Institute-designated comprehensive cancer center. We also aimed to understand
      these patients' understanding of, and attitudes toward, hereditary cancer testing
      and DNA banking. Palliative care in-patients with cancer completed structured
      interviews, and their medical records were reviewed. Among patients at high risk
      for hereditary cancer, we assessed history of genetic testing/DNA banking; and
      related knowledge and attitudes. Among 24 high-risk patients, 14 (58.3%) said
      they/their relatives had genetic testing or they had been referred for a genetics
      consultation. Of the remaining 10 patients, seven (70%) said they would
      "probably" or "definitely" get tested. Patients who had not had testing were
      least concerned about the impact of future testing on their family relationships;
      two (20%) said they were "extremely concerned" about privacy related to genetic
      testing. Of patients without prior testing, five (50%) said they had heard or
      read "a fair amount" about genetic testing. No high-risk patients had banked DNA.
      Overall, 23 (95.8%) said they had heard or read "almost nothing" or "relatively
      little" about DNA banking. Written materials and clinician discussion were most
      preferred ways to learn about genetic testing and DNA banking. Overall, this
      study demonstrates underutilization of genetics services at the end of life
      continues to be problematic, despite high patient interest.

PMID- 29204811
TI  - Impact of a Patient-Facing Enhanced Genomic Results Report to Improve
      Understanding, Engagement, and Communication.
AB  - : "The objective of this study was to" test the effectiveness of an enhanced
      genomic report on patient-centered outcome domains including communication,
      engagement and satisfaction. "Study design utilized" a prospective, randomized,
      mixed-methods desctiptive study of a whole genome sequencing results report,
      GenomeCOMPASSTM, that was accessed by providers through the electronic health
      record and by patients through the associated patient portal. "The study was set
      in" an integrated healthcare delivery system in central Pennsylvania. "Eighty
      four" parents of 46 children with undiagnosed Intellectual Disability, Autism
      Spectrum Disorder and/or multiple congenital anomalies who had participated in a
      previous study offering whole genome sequencing for their affected child were
      invited to enroll. Fifty-two parents enrolled. Following a traditional genetics
      results informing visit, the study coordinator stratified families by diagnostic
      result and uninformative result and then randomized families within each group to
      an intervention arm to receive the GenomeCOMPASSTM report or to the usual care
      arm to receive a summary letter from the medical geneticist. A letter inviting
      enrollment included a baseline survey, which once returned, constituted
      enrollment. Surveys were administered at 3 months post-genetics visit. At 6
      months, the usual care arm crossed over to receive the intervention and were
      administered an additional survey at 3 months. Qualitative interviews were
      conducted following survey completion to augment the survey data regarding the
      patient centered outcomes of interest. Patient reported outcomes including
      communication, engagement, empowerment and satisfaction. In the intervention arm,
      GenomeCOMPASSTM reports were released to 14 families (N = 28 parents) and of
      those 21 (75%) returned 3 month surveys. In the usual care arm, 12 families (N =
      24 parents) received usual care summary letters and of those 20 (83%) returned 3
      month surveys. At crossover, GenomeCOMPASSTM reports were released to 20
      individuals and 15 (75%) returned 3 month surveys. Qualitative interviews were
      conducted with 5 individuals. Use of the GenomeCOMPASSTM report was reported by
      this small group of parents to improve communication with providers and non
      health professionals such as educators and therapists and led to increased
      engagement and high satisfaction. Providers and others involved in the children's
      care also endorsed the report's effectiveness. Reports that addressed negative
      findings, i.e. uninformative results, were not found to be useful. Although the
      number of users was small, this study supports that customizable template reports
      may provide a useful and durable source of information that can support and
      enhance the information provided by genetics professionals in traditional face-to
      face encounters. TRIAL REGISTRATION: Clinicaltrials.gov (Record 2013-0594).

PMID- 29204812
TI  - Tumor Screening in Beckwith-Wiedemann Syndrome: Parental Perspectives.
AB  - Children with Beckwith-Wiedemann Syndrome (BWS) and Isolated Hemihypertrophy
      (IHH) are at an increased risk for developing tumors. Tumor screening in this
      population is currently being reassessed by several groups and the effect on
      patients and patient-families has been argued both as a reason to screen and not
      to screen. Parental perspectives on this topic have never been systematically
      addressed for the BWS population. Here, we conducted a parent-based survey to
      evaluate knowledge and attitudes toward tumor screening in patients affected by
      BWS/IHH. A total of 261 surveys were completed. Overall, parents reported that
      screening decreased their worry and did not feel that screening increased worry
      or created a burden. This effect was observed across various demographic
      variables and other factors examined. Almost all significant differences observed
      could be attributed to parental knowledge of tumor risk. Parents who correctly
      identified their child's tumor risk were more likely to agree with stratified
      screening recommendations according to BWS type and risk, and were less likely to
      feel worried if recommendations were changed. These results highlight the need to
      educate families about their child's genetic type and tumor risk in order to
      facilitate an informed decision about tumor screening.

PMID- 29204813
TI  - The Use of Film Clips in a Viewing Time Task of Sexual Interests.
AB  - Viewing time tasks using still pictures to assess age and gender sexual interests
      have been well validated and are commonly used. The use of film clips in a
      viewing time task would open up interesting possibilities for the study of sexual
      interest toward sexual targets or activities that are not easily captured in
      still pictures. We examined the validity of a viewing time task using film clips
      to assess sexual interest toward male and female targets, in a sample of 52 young
      adults. Film clips produced longer viewing times than still pictures. For both
      men and women, the indices derived from the film viewing time task were able to
      distinguish individuals who identified as homosexual (14 men, 8 women) from those
      who identified as heterosexual (15 men, 15 women), and provided comparable group
      differentiation as indices derived from a viewing time task using still pictures.
      Men's viewing times were more gender-specific than those of women. Viewing times
      to film clips were correlated with participants' ratings of sexual appeal of the
      same clips, and with viewing times to pictures. The results support the
      feasibility of a viewing time measure of sexual interest that utilizes film clips
      and, thus, expand the types of sexual interests that could be investigated (e.g.,
      sadism, biastophilia).

PMID- 29204814
TI  - Commentary on "Gay Male Only-Children: Evidence for Low Birth Weight and High
      Maternal Miscarriage Rates" from the Prenatal Thyroid Model Perspective.

PMID- 29204815
TI  - Sadistic Offender or Sexual Sadism? Taxometric Evidence for a Dimensional
      Structure of Sexual Sadism.
AB  - Severe sexual sadism is a disorder of sexual preferences that focuses on
      humiliation and domination of the victim, sometimes causing grievous injury or
      death. Because offenders with high levels of sadism represent a risk to both
      reoffend and cause considerable harm should they reoffend, a diagnosis of sexual
      sadism has serious implications. The actual diagnosis of sexual sadism is fraught
      with problems (i.e., low reliability and validity) and exhibits poor consistency
      across assessments and studies (Levenson, 2004; Marshall, Kennedy, & Yates,
      2002a). Various authors have proposed that sadism should be reconceptualized and
      have suggested that a dimensional approach may be more effective than a
      classificatory one for diagnosing sexual sadism (e.g., Marshall & Kennedy, 2003;
      Nietschke, Osterheider, & Mokros, 2009b). The dimension versus taxon question
      also impacts debates about the etiology and treatment of sadism. We assessed the
      taxonicity of sexual sadism by conducting a taxometric analysis of the scores of
      474 sex offenders from penitentiary settings on the MTC Sexual Sadism Scale,
      using Meehl's taxometric methods (Meehl & Yonce, 1994; Waller & Meehl, 1998).
      Findings indicated that sexual sadism presents a clear underlying dimensional
      structure. These results are consistent with earlier research supporting a
      dimensional assessment of sexual sadism and indicate that the diagnosis of sexual
      sadism should be reconceptualized. The theoretical and clinical implications of
      these findings are discussed.

PMID- 29204816
TI  - Sexual Health Risk Behavior Disparities Among Male and Female Adolescents Using
      Identity and Behavior Indicators of Sexual Orientation.
AB  - Sexual minority adolescent sexual risk behavior studies often overlook young
      women, do not consider behavior- and identity-based sexual orientation indicators
      in combination, and focus mainly on condomless sex. We examined multiple risk
      behaviors in a large sample of adolescent young men and women using combined
      behavior- and identity-based indices. The 2015 Dane County Youth Assessment data
      included 4734 students in 22 high schools who had ever voluntarily engaged in
      sexual contact (51.7% male; 76.0% White, non-Hispanic). Items assessed having sex
      with unfamiliar partners, sex while using substances, using protection, and STI
      testing. Logistic regressions tested for disparities based on combined identity-
      and behavior-based sexual orientation indicators. For both young men and women,
      youth who reported heterosexual or questioning identities-but who had sex with
      same-sex partners-were at consistently greater risk than heterosexual youth with
      only different-sex partners. Also, for both young men and women, bisexuals with
      partners of both sexes more consistently reported higher risk than heterosexual
      youth than did bisexuals with only different-sex partners. Risk behavior for gay
      young men who had sex only with men mirrored those in extant literature. Risk
      levels differed for specific groups of sexual minority young women, thus
      deserving further attention. Findings underscore the need for sexual health
      research to consider sexual orientation in a more multidimensional manner.

PMID- 29204817
TI  - Oxyphenbutazone promotes cytotoxicity in rats and Hep3B cellsvia suppression of
      PGE2 and deactivation of Wnt/beta-catenin signaling pathway.
AB  - Hepatocellular carcinoma (HCC) is the fifth leading cause of death and is
      generally typified by elevated liver enzyme biomarkers, antioxidants, and chronic
      inflammation of hepatocytes. Although currently available drugs have shown
      remarkable alleviation of the cancerous condition, but at the same time they
      present a more severe challenge of toxic effects due to chemotherapy. Therefore,
      in order to bring more patient-compliant therapy, we aimed to refurbish the use
      of a COX inhibitor, oxyphenbutazone (OPB), with low dose of methotrexate (MTX) to
      treat diethyl nitrosamine (DENA)-induced HCC in Wistar rats and in Hep3B cells.
      Hep3B cells were subjected to assays like in vitro cytotoxicity, DNA synthesis,
      and caspase activity. The combination index was also evaluated, succeeding the
      cytotoxicity assay, to analyze the possible synergism. For in vivo study, Wistar
      strain male rats were given single intraperitoneal dose of DENA (200 mg/kg) and
      were supplied with sodium phenobarbital (0.1% in tap water) for promoting
      tumorigenesis throughout the study. MTX (2.5 and 5.0 mg/kg/week, ip) and OPB (70
      mg/kg/week, po in two divided doses) were administered to the treatment groups
      from 3rd week till the termination of study. Several biochemical parameters
      including biomarkers of liver function, antioxidant enzymes, and
      histopathological examination of liver cells were tested. Significant synergism
      was witnessed in the cytotoxicity assay when Hep3B cells received varied dose
      combination treatment of MTX (0.25, 0.5, or 1.0 umol/L) and OPB (2.5, 5.0, or 7.5
      umol/L). MTX (0.5 and 1.0 umol/L) in combination with OPB (5.0 or 7.5 umol/L)
      inhibited the cell proliferation as BrdU incorporation was quite low in DNA
      synthesis analysis, as well as caspase-9/-3 cascade was activated which led to
      apoptosis of cancer cells. Co-treatment with MTX and OPB exerted potential
      anticancer activity in rats than either of the drugs alone. Administration of
      combination therapy harmonized the DENA-induced elevation of serum biochemical
      parameters, including but not limited to, alpha-fetoprotein (AFP), alanine- and
      aspartate-aminotransferase, alkaline phosphatase, vascular endothelial growth
      factor (VEGF), and antioxidant enzymes like superoxide dismutase (SOD), catalase
      (CAT), and lipid per oxidation (LPO). All these results were optimally
      substantiated by histopathological examination. As evident COX-2 catalyzes the
      synthesis of PGE2, needed in the activation of Wnt/beta-catenin pathway, which in
      turn is responsible for activating the transcriptional proteins required for
      higher degree of cell division and thence growth. Therefore, inhibition of COX-2
      by our novel combination infers that even low doses of MTX can elucidate
      noticeable anticancer activity when paired with OPB.

PMID- 29204818
TI  - Mir-513a-3p contributes to the controlling of cellular migration processes in the
      A549 lung tumor cells by modulating integrin beta-8 expression.
AB  - Lung tumors are a frequent type of cancer in humans and a leading cause of death,
      and the late diagnostic contributes to high mortality rates. New therapeutic
      strategies are needed, and the heptapeptide angiotensin-(1-7) [ang-(1-7)]
      demonstrated the ability to control cancer growth rates and migration in vitro
      and in vivo. However, the possible use of the heptapeptide in clinical trials
      demands deeper analyses to elucidate molecular mechanisms of its effect in the
      target cells. In this study, we investigated relevant elements that control pro
      inflammatory environment and cellular migration, focusing in the post
      transcription mechanism using lung tumor cell line. In our cellular model, the
      microRNA-513a-3p was identified as a novel element targeting ITG-beta8, thereby
      controlling the protein level and its molecular function in the controlling of
      migration and pro-inflammatory environment. These findings provide useful
      information for future studies, using miR-513a-3p as an innovative molecular tool
      to control lung tumor cell migration, which will support more effective clinical
      treatment of the patients with the widely used chemotherapeutic agents,
      increasing survival rates.

PMID- 29204819
TI  - Isolation and molecular identification of lactic acid bacteria from King grass
      and their application to improve the fermentation quality of sweet Sorghum.
AB  - The aim of the present study was isolation and molecular identification of lactic
      acid bacteria from King grass and their application to improve the fermentation
      quality of sweet Sorghum. Seventy-six strains of LAB were isolated; five strains
      were selected for Physiological and morphological tests and 16S rRNA sequencing.
      All five strains grew at different pH 3.5-8.0, different temperature 35, 40, 45,
      50  degrees C and different NaCl concentrations 3, 6.5, 9.5%. Strains HDASK were
      identified Lactobacillus plantarum and SK3907, SK2A32, SK3A42 and ASKDD
      Pediococcus acidilactici. Three isolated strains and one commercial strain were
      added to sweet sorghum. Silage was prepared of four treatments and one control
      with three replicates as control (SKC, adding 2 ml/kg sterilizing water), L.
      plantarum commercial bacteria (SKP), L. plantarum (HDASK) isolated from King
      grass (SKA), P. acidilactici (SK3907) isolated from King grass (SKB) and P.
      acidilactici (ASKDD) isolated from King grass (SKD). All silage were prepared
      using polyethylene terephthalate bottles, and incubated at room temperature for
      different ensiling days. The level of pH, acetic acid, NH3-N, water soluble
      carbohydrate and butyric acid was significantly (P < 0.05) decreased. Lactic
      acid, ethanol and propionic acid (PA) was significantly (P < 0.05) increased in
      treatments compared to control. The dry matter, propionic acid neutral detergent
      fiber, acid detergent fiber did not significantly (P < 0.05) differ among the
      treatments but the values were increased and decreased. The number of yeast, mold
      and LAB were significantly (P < 0.05). It is suggested that the supplementation
      of LAB could enhanced the fermentation quality of sweet Sorghum silage.

PMID- 29204820
TI  - Identification of syllables best recognized in acoustic-stimulated functional
      magnetic resonance imaging.
AB  - In acoustic-stimulated functional magnetic resonance imaging (fMRI), tasks are
      performed by subjects either during imaging in the presence of scanning noise or
      during non-imaging periods without scanning noise. Suitable syllables for voice
      tasks performed with MRI-compatible headphones are limited during the imaging
      period with scanning noise. However, suitable syllables for voice tasks during
      the non-imaging period, without scanning noise, are not yet known. This study
      aimed to identify suitable syllables for voice tasks during both imaging and non
      imaging periods. The subjects were 12 healthy volunteers who were native Japanese
      speakers. On an answer sheet attached to a wooden board, they were asked to write
      down the syllables they perceived through MRI-compatible headphones during
      imaging and non-imaging periods. The rate of accuracy for the perception of
      syllables was calculated; optimally perceived syllables were defined by a rate of
      accuracy exceeding the 95% upper confidence limit (UCL). The accuracy of syllable
      perception was significantly higher (P < 0.01) during the non-imaging period
      (77.2 +/- 5.6%) than during the imaging period (66.3 +/- 5.0%). The 95% UCLs
      obtained from the rates of accuracy were 83.5% during imaging and 88.9% during
      the non-imaging period. The number of syllables for which the accuracy rate
      exceeded the 95% UCL was 28 during imaging and 33 during the non-imaging period.
      These syllables could be used for voice tasks in acoustic-stimulated fMRI during
      imaging or non-imaging periods.

PMID- 29204821
TI  - Development of a clinical prediction score for detection of suspected cases of
      equine grass sickness (dysautonomia) in France.
AB  - Equine grass sickness (EGS) (equine dysautonomia) is a neurodegenerative
      condition of grazing equines. Pre-mortem diagnosis of EGS is a challenge for
      practitioners as definitive diagnosis requires ileal/myenteric lymph node
      biopsies. This study aimed to develop a clinical score that could be used by
      practitioners to improve the detection of acute or subacute EGS cases in the
      field. Suspected EGS cases were declared by veterinary practitioners. A case was
      classified as confirmed positive if ileal or rectal biopsy samples showed
      neuronal degeneration typical of EGS. A semi-quantitative scoring system,
      including epidemiological and clinical data, was created to attempt to classify
      suspected EGS horses into confirmed positive or negative cases. Each variable was
      weighted based on a boosted regression trees model, while taking into account its
      clinical relevance. Twenty-eight EGS cases were confirmed by biopsy during the
      entire study period. The best cut-off value for the score to have a high
      sensitivity while maximizing specificity was 8, with a sensitivity of 100% and a
      specificity of 53%. In our dataset, 77% of animals would be correctly classified
      with this cut-off value of 8. Highest sensitivity was chosen in order to detect
      the highest number of potential cases. Our score represents an inexpensive and
      useful tool to aid in the identification of suspected EGS cases in the field and
      selection for further diagnostics procedures to confirm or rule out the disease.
      Application of the score to larger populations of animals would be required to
      further adapt and refine the score.

PMID- 29204822
TI  - The experience of the RIPO, a shoulder prosthesis registry with 6-year follow-up.
AB  - BACKGROUND: Implant registries have proved valuable in assessing the outcomes of
      arthroplasty procedures. Moreover, by identifying lesser quality implants they
      have indirectly improved the quality of care. The registry of prosthetic shoulder
      implants was established in 2008. METHODS: It records information on all types of
      primary and revision arthroplasty procedures involving the glenohumeral joint,
      including reverse and total arthroplasty, hemiarthroplasty, resurfacing, removal,
      and any other surgical procedures that are required to manage these patients. The
      collected data include patient demographics, weight, height, operated side, cuff
      status, and diagnosis/reason for revision surgery, information on previous
      surgical procedures involving either shoulder, comorbidities, antibiotic and
      thromboembolic prophylaxis, blood transfusions, surgical approach, cuff repair
      procedures performed during arthroplasty, bone grafts, drains, and perioperative
      complications, and data about the prosthetic components implanted, including the
      fixation method. RESULTS: Procedures were performed on 3754 shoulders. They
      included 2226 RSA, 320 TSA, 730 HA, 233 resurfacing procedures, 245 revisions,
      and 77 "other" procedures. The survival curves of the implants are greater than
      90%, and no differences were found among prosthesis from different manufacturers.
      The diagnosis that prompted to arthroplasty was: osteoarthritis in 60.9% of cases
      and fractures, bone necrosis, sequelae of fracture and rotator cuff tear
      arthropathy for the rest of implants. DISCUSSION AND CONCLUSION: This study
      describes the epidemiological data and mid-term implant outcomes of the shoulder
      arthroplasty procedures performed in our region, from 2008 to 2014, and compares
      them with published data from national registries of similar size. LEVEL OF
      EVIDENCE: III.

PMID- 29204823
TI  - Balancing Antibacterial Efficacy and Reduction in Renal Function to Optimise
      Initial Gentamicin Dosing in Paediatric Oncology Patients.
AB  - This study aimed to determine the optimal starting dose of gentamicin in
      paediatric oncology patients. A population pharmacokinetic model describing drug
      exposure, a semi-mechanistic model describing bacterial killing and an Emax model
      describing renal cortex accumulation were linked in a utility function using
      NONMEM(r). The optimal gentamicin starting dose was estimated in patients aged
      from 0.1 to 18.2 years, by balancing the probability of efficacy on day 1 against
      relative renal function reduction on day 7 with continued dosing. Using
      achievement of a gentamicin area under the concentration time curve to bacterial
      minimum inhibitor concentration (MIC) ratio of >= 100 and maximum concentration
      to MIC ratio of >= 10 as the efficacy endpoints, a starting dose of 7.1, 9.5,
      10.8 and 14.6 mg/kg/q24h was optimal at a MIC of 0.5, 1, 2 and 4 mg/L
      respectively, with >= 75% probability of obtainment. Using achievement of a 2
      log10 bacterial count reduction at 24-h post-dose as the efficacy endpoint, a
      starting dose of 12.8 mg/kg/q24h was optimal, with 85.6% probability of
      obtainment. Under these different dosing scenarios, relative reduction in renal
      function ranged on average from 6.9 to 14.5% on day 7. The current recommended
      starting dose of gentamicin of 7.5 mg/kg/q24h may not be sufficient to achieve
      efficacy on day 1 if bacterial MIC is > 0.5 mg/L. A higher initial dose (up to
      14.6 mg/kg/q24h), in less sensitive microorganisms, would likely cause only a
      relatively small reduction in renal function at day 7. Close monitoring is
      crucial if high doses are given, especially for longer than 7 days.

PMID- 29204825
TI  - Stem Cell Microenvironments and Beyond.
AB  - Endogenous stem cells are indispensable to keep tissue homeostasis due to their
      unique ability to generate more specialized cell types in an organized way
      depending on the body needs. Precise control over stem cell differentiation is
      essential for organogenesis and tissue homeostasis. Stem cells reside in
      specialized microenvironments, also called niches, which maintain them in an
      undifferentiated and self-renewing state. The cellular and molecular mechanisms
      of stem cell maintenance are key to the regulation of homeostasis and likely
      contribute to several disorders when altered during adulthood. Extensive studies
      in a various tissues have shown the importance of the niche in modulating stem
      cell behavior, including bone marrow, skin, intestine, skeletal muscle, vocal
      cord, brain, spinal cord, stomach, esophagus, and others. In recent past,
      extraordinary advancement has been made in the identification and
      characterization of stem cell niches using modern state-of-art techniques. This
      progress lead to the definition of the main cellular components in the
      microenvironment where stem cells reside and the identification of molecular
      mechanisms by which stem cell behavior is controlled, revealing key niche signals
      involved in stem cell regulation. Similar to the ecological niche of an organism,
      a stem cell niche is exclusive to the specific type of stem cell and guides its
      dynamics. This book describes the major cellular and molecular components of
      various stem cells microenvironments in different organs and at distinct
      pathophysiological conditions, such as cell-cell interactions, extra-cellular
      matrix proteins, soluble factors, and physical forces. Although several advances
      have been made in our understanding of the signals that promote stem cell
      activation or quiescence, several components of the stem cells microenvironment
      remain unknown due to the complexity of niche composition and its dynamics.
      Further insights into these cellular and molecular mechanisms will have important
      implications for our understanding of organ homeostasis and disease. In this
      book, we present a selected collection of detailed chapters on what we know so
      far about the stem cell niches in various tissues and under distinct
      pathophysiological conditions. Twelve chapters written by experts in the field
      summarize the present knowledge about the physiological function and
      pathophysiological role of the stem cell regulation by the microenvironment.

PMID- 29204824
TI  - Chemoinformatics: a perspective from an academic setting in Latin America.
AB  - This perspective discusses the current progress of a chemoinformatics group in a
      major university in Latin America. Three major aspects are discussed in a
      critical manner: research, education, and collaboration with industry and other
      public research networks. It is also presented an overview of the progress in
      applied research and development of research concepts. Efforts to teach
      chemoinformatics at the undergraduate and graduate levels are discussed. It is
      addressed how the partnership with industry and other not-for-profit research
      institutions not only brings additional sources of funding but, more importantly,
      increases the impact of the multidisciplinary work and offers the students to be
      exposed to other research environments. We also discuss the main perspectives and
      challenges that remain to be addressed in these settings.

PMID- 29204826
TI  - The Bone Marrow Microenvironment for Hematopoietic Stem Cells.
AB  - The main function of the microenvironment in the bone marrow (BM) is to provide
      signals that regulate and support the production of the billions of blood cells
      necessary to maintain homeostasis. The best characterized BM microenvironment is
      the niche that regulates hematopoietic stem cells. Efforts from many different
      laboratories have revealed that the niche is mainly perivascular and that blood
      vessels and perivascular stromal cells are the key components. In addition
      numerous cell types have been shown to be components of the niche. Here we
      discuss our current understanding of the niche and the evidence supporting the
      role of different types of cells in regulating hematopoietic stem cell numbers
      and function in vivo.

PMID- 29204827
TI  - Leukemia Stem Cells Microenvironment.
AB  - The dynamic interactions between leukemic cells and bone marrow (BM) cells in the
      leukemia BM microenvironment regulate leukemia stem cell (LSC) properties
      including localization, self-renewal, differentiation, and proliferation. Recent
      research of normal and leukemia BM microenvironments has revealed several key
      components of specific niches that provide a sanctuary where subpopulations of
      leukemia cells evade chemotherapy-induced death and acquire a drug-resistant
      phenotype, as well as the molecular pathways critical for
      microenvironment/leukemia interactions. Although the biology of LSCs shares many
      similarities with that of normal hematopoietic stem cells (HSCs), LSCs are able
      to outcompete HSCs and hijack BM niches. Increasing evidence indicates that these
      niches fuel the growth of leukemia cells and contribute to therapeutic resistance
      and the metastatic potential of leukemia cells by shielding LSCs. Not only
      "microenvironment-induced oncogenesis," but also a "malignancy-induced
      microenvironment" have been proposed. In this chapter, the key components and
      regulation of BM niches in leukemic BM is described. In addition, metabolic
      changes in LSCs, which are currently a subject of intense investigation, will
      also be discussed to understand LSC survival.

PMID- 29204829
TI  - Spinal Cord Stem Cells In Their Microenvironment: The Ependyma as a Stem Cell
      Niche.
AB  - The ependyma of the spinal cord is currently proposed as a latent neural stem
      cell niche. This chapter discusses recent knowledge on the developmental origin
      and nature of the heterogeneous population of cells that compose this stem cell
      microenviroment, their diverse physiological properties and regulation. The
      chapter also reviews relevant data on the ependymal cells as a source of
      plasticity for spinal cord repair.

PMID- 29204828
TI  - Developmental HSC Microenvironments: Lessons from Zebrafish.
AB  - Hematopoietic stem cells (HSCs) posses the ability to maintain the blood system
      of an organism from birth to adulthood. The behavior of HSCs is modulated by its
      microenvironment. During development, HSCs acquire the instructions to self-renew
      and differentiate into all blood cell fates by passing through several
      developmental microenvironments. In this chapter, we discuss the signals and cell
      types that inform HSC decisions throughout ontogeny with a focus on HSC
      specification, mobilization, migration, and engraftment.

PMID- 29204830
TI  - Being a Neural Stem Cell: A Matter of Character But Defined by the
      Microenvironment.
AB  - The cells that build the nervous system, either this is a small network of
      ganglia or a complicated primate brain, are called neural stem and progenitor
      cells. Even though the very primitive and the very recent neural stem cells
      (NSCs) share common basic characteristics that are hard-wired within their
      character, such as the expression of transcription factors of the SoxB family,
      their capacity to give rise to extremely different neural tissues depends
      significantly on instructions from the microenvironment. In this chapter we
      explore the nature of the NSC microenvironment, looking through evolution,
      embryonic development, maturity and even disease. Experimental work undertaken
      over the last 20 years has revealed exciting insight into the NSC microcosmos.
      NSCs are very capable in producing their own extracellular matrix and in
      regulating their behaviour in an autocrine and paracrine manner. Nevertheless,
      accumulating evidence indicates an important role for the vasculature, especially
      within the NSC niches of the postnatal brain; while novel results reveal direct
      links between the metabolic state of the organism and the function of NSCs.

PMID- 29204831
TI  - Glioblastoma Stem Cells and Their Microenvironment.
AB  - Glioblastoma (GBM) is the most common primary malignant astrocytoma associated
      with a poor patient survival. Apart from arising de novo, GBMs also occur due to
      progression of slower growing grade III astrocytomas. GBM is characterized by
      extensive hypoxia, angiogenesis, proliferation and invasion. Standard treatment
      options such as surgical resection, radiation therapy and chemotherapy have
      increased median patient survival to 14.6 months in adults but recurrent disease
      arising from treatment resistant cancer cells often results in patient mortality.
      These treatment resistant cancer cells have been found to exhibit stem cell like
      properties. Strategies to identify or target these Glioblastoma Stem Cells (GSC)
      have proven to be unsuccessful so far. Studies on cancer stem cells (CSC) within
      GBM and other cancers have highlighted the importance of paracrine signaling
      networks within their microenvironment on the growth and maintenance of CSCs. The
      study of GSCs and their communication with various cell populations within their
      microenvironment is therefore not only important to understand the biology of
      GBMs but also to predict response to therapies and to identify novel targets
      which could stymy support to treatment resistant cancer cells and prevent disease
      recurrence. The purpose of this chapter is to introduce the concept of GSCs and
      to detail the latest findings indicating the role of various cellular subtypes
      within their microenvironment on their survival, proliferation and
      differentiation.

PMID- 29204833
TI  - The Macula Flava of the Human Vocal Fold as a Stem Cell Microenvironment.
AB  - 1. There is growing evidence to suggest that the cells in the maculae flavae are
      tissue stem cells of the human vocal fold and maculae flavae are a candidate for
      a stem cell niche. 2. The latest research shows that the cells in the human
      maculae flavae are involved in the metabolism of extracellular matrices that are
      essential for the viscoelasticity in the human vocal fold mucosa as a vibrating
      tissue, and considered to be important cells in the growth, development, and
      aging of the human vocal fold mucosa. 3. The cells in the human maculae flavae
      possess proteins of all three germ layers, indicating they are undifferentiated
      and have the ability of multipotency. 4. The cell division in the human adult
      maculae flavae is reflective of asymmetric self-renewal and cultured cells form a
      colony-forming unit. Therefore, the phenomenon gives rise to the strong
      possibility that the cells in the human maculae flavae are tissue stem cells. 5.
      Recent research suggests that the cells in the human maculae flavae arise from
      the differentiation of bone marrow cells via peripheral circulation. 6. The
      hyaluronan concentration in the maculae flavae is high and contains cells which
      possess hyaluronan receptors, indicating that the maculae flavae are hyaluronan
      rich matrix, which is required for a stem cell niche. 7. A proper
      microenvironment in the maculae flavae of the human vocal fold mucosa is
      necessary to be effective as a stem cell niche maintaining the stemness of the
      contained tissue stem cells.

PMID- 29204835
TI  - Oral Cancer Stem Cells Microenvironment.
AB  - Cancer stem cells (CSCs) play important role in tumor growth and metastasis
      coupled with increased recurrences and acquired therapeutic resistance in oral
      cancer. The tumor microenvironment imposes intense pressure in cancer evolution
      in response to adverse growth conditions, resource limitation and immune
      predation. Here, we discussed the dynamic interplay between cancer stem cells and
      tumor microenvironment in the formation of intratumoral heterogeneity to modulate
      tumor progression. The CSCs niche provide a special microhabitat for survival,
      maintenance of stemness and tumor re-propagation. Moreover, adaptive cellular
      behavior might be driven by tough tumor microenvironmental selective forces which
      highly regulate alterations in the gene expression leading to the reprogramming
      of signaling pathways generating stem-like characteristics, adaptive metabolic
      plasticity and energy fueling with autophagy to permit the CSCs to sustain in the
      ever changing microenvironments during tumor progression. On the other hand, CSCs
      also direct the tumor microenvironment modulation and remodeling in its favour.
      The cytokines, chemokines and growth factors released from CSCs regulates
      neoangiogensis, differentiation, degradation of matrix protein and immune
      suppression favoring tumor-promoting conditions and initiates multiple signaling
      cascades augmenting the tumor progression.

PMID- 29204832
TI  - Plasticity of the Muscle Stem Cell Microenvironment.
AB  - Satellite cells (SCs) are adult muscle stem cells capable of repairing damaged
      and creating new muscle tissue throughout life. Their functionality is tightly
      controlled by a microenvironment composed of a wide variety of factors, such as
      numerous secreted molecules and different cell types, including blood vessels,
      oxygen, hormones, motor neurons, immune cells, cytokines, fibroblasts, growth
      factors, myofibers, myofiber metabolism, the extracellular matrix and tissue
      stiffness. This complex niche controls SC biology-quiescence, activation,
      proliferation, differentiation or renewal and return to quiescence. In this
      review, we attempt to give a brief overview of the most important players in the
      niche and their mutual interaction with SCs. We address the importance of the
      niche to SC behavior under physiological and pathological conditions, and finally
      survey the significance of an artificial niche both for basic and translational
      research purposes.

PMID- 29204834
TI  - Oesophageal Stem Cells and Cancer.
AB  - Oesophageal cancer remains one of the least explored malignancies. However, in
      recent years its increasing incidence and poor prognosis have stimulated interest
      from the cancer community to understand the pathways to the initiation and
      progression of the disease.Critical understanding of the molecular processes
      controlling changes in stem cell fate and the cross-talk with their adjacent
      stromal neighbours will provide essential knowledge on the mechanisms that go
      awry in oesophageal carcinogenesis. Advances in lineage tracing techniques have
      represented a powerful tool to start understanding changes in oesophageal cell
      behaviour in response to mutations and mutagens that favour tumour
      development.Environmental cues constitute an important factor in the aetiology of
      oesophageal cancer. The oesophageal epithelium is a tissue exposed to harsh
      conditions that not only damage the DNA of epithelial cells but also result in an
      active stromal reaction, promoting tumour progression. Ultimately, cancer
      represents a complex interplay between malignant cells and their
      microenvironment. Indeed, increasing evidence suggests that the accumulation of
      somatic mutations is not the sole cause of cancer. Instead, non-cell autonomous
      components, coming from the stroma, can significantly contribute from the
      earliest stages of tumour formation.The realisation that stromal cells play an
      important role in cancer has transformed this cellular compartment into an
      attractive and emerging field of research. It is becoming increasingly clear that
      the tumour microenvironment provides unique opportunities to identify early
      diagnostic and prognostic markers, as well as potential therapeutic strategies
      that may synergise with those targeting tumour cells.This chapter compiles recent
      observations on oesophageal epithelial stem cell biology, and how environmental
      and micro-environmental changes may lead to oesophageal disease and cancer.

PMID- 29204836
TI  - Fetal Membranes-Derived Stem Cells Microenvironment.
AB  - Recently, the regenerative medicine has been trying to congregate different areas
      such as tissue engineering and cellular therapy, in order to offer effective
      treatments to overcome several human and veterinary medical problems. In this
      regard, fetal membranes have been proposed as a powerful source for obtainment of
      multipotent stem cells with low immunogenicity, anti-inflammatory properties and
      nontumorigenicity properties for the treatment of several diseases, including
      replacing cells lost due to tissue injuries or degenerative diseases. Morpho
      physiological data have shown that fetal membranes, especially the yolk sac and
      amnion play different functions according to the gestational period, which are
      direct related to the features of the microenvironment that their cells are
      subject. The characteristics of the microenvironment affect or controls important
      cellular events involved with proliferation, division and maintenance of the
      undifferentiated stage or differentiation, especially acting on the extracellular
      matrix components. Considering the importance of the microenvironment and the
      diversity of embryonic and fetal membrane-derived stem cells, this chapter will
      addressed advances in the isolation, phenotyping, characteristics of the
      microenvironment, and applications of yolk sac and amniotic membrane-derived stem
      cells for human and veterinary regenerative medicine.

PMID- 29204837
TI  - Current Technologies Based on the Knowledge of the Stem Cells Microenvironments.
AB  - The stem cell microenvironment or niche plays a critical role in the regulation
      of survival, differentiation and behavior of stem cells and their progenies.
      Recapitulating each aspect of the stem cell niche is therefore essential for
      their optimal use in in vitro studies and in vivo as future therapeutics in
      humans. Engineering of optimal conditions for three-dimensional stem cell culture
      includes multiple transient and dynamic physiological stimuli, such as blood flow
      and tissue stiffness. Bioprinting and microfluidics technologies, including
      organs-on-a-chip, are among the most recent approaches utilized to replicate the
      three-dimensional stem cell niche for human tissue fabrication that allow the
      integration of multiple levels of tissue complexity, including blood flow. This
      chapter focuses on the physico-chemical and genetic cues utilized to engineer the
      stem cell niche and provides an overview on how both bioprinting and
      microfluidics technologies are improving our knowledge in this field for both
      disease modeling and tissue regeneration, including drug discovery and toxicity
      high-throughput assays and stem cell-based therapies in humans.

PMID- 29204838
TI  - Volumetric response of progressing post-SRS lesions treated with laser
      interstitial thermal therapy.
AB  - We analyzed volumetric response of metastatic brain tumors that progressed
      despite treatment with stereotactic radiosurgery (SRS) after treatment with laser
      interstitial thermal therapy (LITT). We retrospectively reviewed consecutive
      patients treated from 1/2012 to 10/2015 with LITT for metastatic brain tumors
      demonstrating progression after SRS. Volumes were quantified using MRI with
      contrast-enhanced T1-weighted (T1W) and fluid-attenuated inversion recovery
      (FLAIR). Fifty lesions from 36 patients were studied. Lesions were assessed prior
      to LITT, immediately after LITT, 0-90 days after LITT, 90-180 days after LITT,
      180-270 days after LITT, and 270-360 days after LITT. The median T1W volume was
      5.05 cc (range 0.54-23.31 cc) before LITT treatment (n = 50), 7.70 cc (range 1.72
      38.76 cc) 0-90 days after LITT (n = 47), and 3.68 cc (range 1.282-48.31 cc) 180
      270 days after LITT (n = 21). The median FLAIR volume was 43.36 cc (range 3.09
      233.01 cc) before LITT treatment (n = 50), 37.13 cc (range 3.48-244.23 cc) 0-90
      days after LITT (n = 43), 31.68 cc (range 1.6-248.75 cc) 180-270 days after LITT
      (n = 18). The 6-month FLAIR volume showed a statistically significant reduction
      compared to pretreatment (p = 0.04). After selecting for cases where patients had
      two or more post-operative MRIs, we found that 24 lesions (63%) demonstrated an
      overall downward trend and 14 lesions (37%) demonstrated an upward trend. The
      median pre-treatment T1W volume for the patients whose lesions demonstrated
      volumetric reduction after LITT was 3.54 cc (range 0.539-10.06 cc) and for those
      who did not demonstrate volumetric reduction after LITT it was 8.81 cc (range
      0.926-23.313 cc). The pre-treatment tumor volume plays a significant role in
      determining response to LITT with smaller tumor volumes responding better to LITT
      than tumors with larger volumes.

PMID- 29204839
TI  - Prognostic value of a microRNA signature as a novel biomarker in patients with
      lower-grade gliomas.
AB  - MicroRNAs (miRNAs) may act as prognostic biomarkers in a variety of cancers. The
      aim of this study was to identify and evaluate a prognostic miRNA signature in
      patients with lower-grade gliomas (LGGs). miRNA expression profiles and clinical
      data of patients with LGGs from the Chinese Glioma Genome Atlas (CGGA; the
      training cohort) and The Cancer Genome Atlas (TCGA; the validation cohort) were
      analyzed, and the least absolute shrinkage and selection operator Cox regression
      model was used to identify the miRNA signature, which was combined with clinical
      prognostic factors to develop an individualized survival prediction model. Gene
      ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis
      were conducted to reveal the biological implications of the signature. We
      identified a four-miRNA signature that stratified patients in the training cohort
      into low- or high-risk groups according to overall survival time, a finding that
      was verified in the validation cohort. Multivariate Cox regression analysis
      indicated that the four-miRNA signature was an independent prognostic biomarker,
      and a nomogram combining this miRNA signature with clinicopathological and
      molecular factors showed high prognostic accuracy for individualized survival
      prediction in both TCGA (C-index = 0.83) and CGGA (C-index = 0.68) cohorts.
      Functional annotation indicated that the major biological processes of this
      prognostic miRNA signature were enriched in cell cycle and DNA repair-associated
      biological processes. Our findings indicated that our newly discovered four-miRNA
      signature may be an effective independent prognostic factor for the prediction of
      patients with LGGs.

PMID- 29204840
TI  - Survival outcomes in pediatric recurrent high-grade glioma: results of a 20-year
      systematic review and meta-analysis.
AB  - Recurrent pediatric high-grade glioma is a leading cause of cancer-related death
      in children. We report results of a systematic review and meta-analysis
      investigating survival outcome in pediatric patients with recurrent high-grade
      glioma over the last 20 years. MEDLINE/PubMed, EMBASE, Web of Science and
      Cochrane Review databases were searched for relevant studies reporting on
      survival outcomes for pediatric patients with recurrent high-grade glioma treated
      between 1996 and 2016. Progression-free survival (PFS) and overall survival (OS)
      were calculated cumulatively over all studies, by therapy subgroup, and by decade
      of treatment. Random effects models were used to control for heterogeneity as
      measured by the I2 statistic. A total of 17 studies across 4 treatment strategies
      were included. Eleven investigated traditional chemotherapy, 1 investigated
      targeted therapy, 3 investigated immunotherapy, and 2 investigated radiotherapy.
      A total of 129 patients were included with a median age of 10.0 years. Cumulative
      PFS was 3.5 months (95% CI 2.1-5.0). Cumulative OS was 5.6 months (95% CI 3.9
      7.3). OS was 4.0 months (95% CI 1.9-6.1) using traditional chemotherapy, 9.3
      months using targeted therapies (95% CI 5.4-13), 6.9 months using immunotherapy
      (95% CI 2.1-12), and 14 months using reirradiation (95% CI 2.8-25). OS between
      1996 and 2006 was 4.2 months (95% CI 2.1-6.2) compared to 8.5 months (95% CI 5.6
      11) after 2006. Pediatric patients with recurrent high-grade glioma suffer from
      poor PFS and OS, regardless of therapy. There may be a trend towards improved OS
      in the last decade.

PMID- 29204841
TI  - Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic
      review and meta-analysis.
AB  - Hemangioblastomas are rare, benign, vascular tumors of the central nervous system
      (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic
      options include microsurgical resection or stereotactic radiosurgery (SRS). With
      no randomized controlled studies and minimal data beyond single-institution
      reviews, the optimal management approach for patients with CNS hemangioblastomas
      is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to
      January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant
      articles were identified and reviewed in accordance to the Preferred Reporting
      Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met
      eligibility criteria for qualitative synthesis, representing 596 subjects and
      1535 tumors. The Gamma Knife was the most published SRS method for CNS
      hemangioblastomas. After critical study appraisal for intra-study bias, 14
      studies were used for quantitative meta-analysis of 5-year progression free
      survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No
      difference was observed between spine versus intracranial studies. Individual
      patient data (IPD) was extracted from 14 studies, representing 322 tumors.
      Univariate analysis of IPD revealed that VHL patients were younger, and had
      smaller tumors compared to those with sporadic disease. Adverse events were
      associated with increasing marginal dose, independent of tumor volume. VHL
      status, sex, radiosurgical method, tumor location, and tumor volume were not
      found to be significantly associated with tumor progression. Multiple studies
      show excellent tumor control at 5-year follow up, however, the long-term efficacy
      of SRS for CNS hemangioblastomas still needs to be investigated, and the studies
      exploring the role of SRS for early treatment of asymptomatic lesions is wanting.

PMID- 29204842
TI  - The Role of Social Context in Racial Disparities in Self-Rated Health.
AB  - Race disparities in self-rated health in the USA are well-documented, such that
      African Americans rate their health more poorly than whites. However, after
      adjusting for health status, socioeconomic status (SES), and health behaviors,
      residual race differences are observed. This suggests the importance of
      unmeasured variables. Because African Americans and whites tend to live in
      differing social contexts, it is possible that accounting for social and
      environmental conditions may reduce racial disparities in self-rated health.
      Differences in self-rated health among whites and African Americans were assessed
      in a low-income, urban integrated community (Exploring Health Disparities in
      Integrated Communities (EHDIC)) and compared with a national sample (National
      Health Interview Survey (NHIS)). Controlling for demographics, SES, health
      insurance, status, and behaviors, African Americans in NHIS had higher odds of
      reporting fair or poor health (odds ratio [OR] = 1.40, 95% confidence interval
      [CI] = 1.18-1.66) than whites. In EHDIC, there was no race difference in self
      rated health (OR = 0.83, 95% CI = 0.63-1.11). These results demonstrate the
      importance of social context in understanding race disparities in self-rated
      health.

PMID- 29204843
TI  - Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug
      Users in Italy.
AB  - So far, only three small outdated studies have investigated hepatitis C virus
      (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus,
      during 2007-2010, we conducted a prospective cohort study among DUs attending 17
      Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV
      uninfected DUs were prospectively followed by interview and anti-HCV antibody and
      RNA testing every 6 months. Incidence was calculated using the person-years
      method. Infection predictors were assessed by time-dependent Cox analysis.
      Participants were mostly male (83.4%), under opioid substitution therapy (OST)
      (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of
      224 DUs initially under OST interrupted treatment during the follow-up. Overall
      HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals
      (CI), 3.63-9.38]. The incidence did not significantly differ according the
      participants' sociodemographic characteristics or the degree of urbanization of
      the towns involved in the study. The incidence was higher for DUs under than for
      those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher
      for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p
      = 0.55). However, all these differences were non-significant. At last follow-up
      visit, a significant decrease in frequency of sharing equipment for
      preparation/using drugs (by injection or not) was observed by analyzing either
      the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted
      independently associated with sharing drug preparation/use equipment,
      backloading, having a HCV-positive sexual partner, or household and (marginally)
      intravenous injection. In this study, HCV incidence was non-negligible and OST
      seemed to lack effectiveness in reducing it. In Italy, implementation of combined
      harm reduction interventions and antiviral treatment of chronically infected DUs
      would be needed.

PMID- 29204844
TI  - Homicides, Public Goods, and Population Health in the Context of High Urban
      Violence Rates in Cali, Colombia.
AB  - Obesity and frequent mental and physical distress are often associated with major
      health problems. The characteristics of the urban environment, such as homicide
      rates and public goods provision, play an important role in influencing
      participation in physical activity and in overall mental health. This study aimed
      to determine whether there was a relationship between homicide rates and public
      goods provision on the health outcomes of the citizens of Cali, Colombia, a city
      known for its high urban violence rate and low municipal investment in public
      goods. We used a linear probability model to relate homicide rates and public
      goods provision (lighted parks, effective public space per inhabitant, and bus
      stations) at the district level to health outcomes (obesity and frequent mental
      and physical distress). Individual data were obtained from the 2014 CaliBRANDO
      survey, and urban context characteristics were obtained from official government
      statistics. After controlling for individual covariates, results showed that
      homicide rates were a risk factor in all examined outcomes. An increase in 1.0 m2
      of public space per inhabitant reduced the probability of an individual being
      obese or overweight by 0.2% (95% confidence interval (CI) = - 0.004 to - 0.001)
      and the probability of frequent physical distress by 0.1% (95% CI = - 0.002 to -
      0.001). On average, the presence of one additional bus station increased the
      probability of being obese or overweight by 1.1%, the probability of frequent
      mental distress by 0.3% (95% CI = 0.001-0.004), and the probability of frequent
      physical distress by 0.02% (95% CI = 0.000-0.003). Living in districts with
      adequate public space and lighted parks lowers the probability of being obese and
      high homicide rates, which are correlated with poor health outcomes in Cali,
      Colombia. Investments in public goods provision and urban safety to reduce
      obesity rates may contribute to a better quality of life for the population.

PMID- 29204845
TI  - Six-Month Emergency Department Use among Older Adults Following Jail
      Incarceration.
AB  - Although the number of older adults who are arrested and subject to incarceration
      in jail is rising dramatically, little is known about their emergency department
      (ED) use or the factors associated with that use. This lack of knowledge impairs
      the ability to design evidence-based approaches to care that would meet the needs
      of this population. This 6-month longitudinal study aimed to determine the
      frequency of 6-month ED use among 101 adults aged 55 or older enrolled while in
      jail and to identify factors associated with that use. The primary outcome was
      self-reported emergency department use within 6 months from baseline. Additional
      measures included baseline socio-demographics, physical and mental health
      conditions, geriatric factors (e.g., recent falls, incontinence, functional
      impairment, concern about post-release safety), symptoms (pain and other
      symptoms), and behavioral and social health risk factors (e.g., substance use
      disorders, recent homelessness). Chi-square tests were used to identify baseline
      factors associated with ED use over 6 months. Participants (average age 60)
      reported high rates of multimorbidity (61%), functional impairment (57%), pain
      (52%), serious mental illness (44%), recent homelessness (54%), and/or substance
      use disorders (69%). At 6 months, 46% had visited the ED at least once; 21%
      visited multiple times. Factors associated with ED use included multimorbidity (p
      = 0.01), functional impairment (p = 0.02), hepatitis C infection (p = 0.01), a
      recent fall (p = 0.03), pain (p < 0.001), loneliness (p = 0.04), and safety
      concerns (p = 0.01). In this population of older adults in a county jail,
      geriatric conditions and distressing symptoms were common and associated with 6
      month community ED use. Jail is an important setting to develop geriatric care
      paradigms aimed at addressing comorbid medical, functional, and behavioral health
      needs and symptomatology in an effort to improve care and decrease ED use in the
      growing population of criminal justice-involved older adults.

PMID- 29204846
TI  - The Costly Consequences of not Being Socially and Behaviorally Ready to Learn by
      Kindergarten in Baltimore City.
AB  - Social, emotional, and behavioral skills are foundational to learning and long
      term success. However, poverty and exposure to adverse childhood experiences
      reduce the chances of children entering kindergarten socially-behaviorally ready
      to learn. This study examined the unique impact of 5-year-old children (N =
      11,412) entering kindergarten not socially-behaviorally ready on three costly
      school outcomes by fourth grade in Baltimore City Public Schools: being retained
      in grade, receiving services and supports through an IEP or 504 plan, and being
      suspended/expelled. Controlling for all other types of school readiness, students
      not identified as socially-behaviorally ready for kindergarten were more likely
      to experience all three school outcomes. Findings underscore the importance of
      early prevention and intervention strategies targeting parents and social
      behavioral readiness skills during the first 5 years of life.

PMID- 29204847
TI  - Adjuvant chemotherapeutic treatment of 1650 patients with early breast cancer in
      routine care in Germany: data from the prospective TMK cohort study.
AB  - BACKGROUND: Several regimens for which efficacy was established in randomized
      controlled trials are recommended in current treatment guidelines for early
      breast cancer. However, knowledge on use and effectiveness of commonly
      administered chemotherapeutic agents in real-life care and across all breast
      cancer subtypes is limited. METHODS: The prospective, multicentre German TMK
      cohort study (Tumour Registry Breast Cancer) recruited patients in 148 oncology
      outpatient-centres. Data from 1650 patients who completed adjuvant chemotherapy
      were analysed regarding treatment regimens and taxane use from 2007 to 2014. The
      association of patient characteristics with application of taxane-free regimens
      was examined with a multivariate regression model. RESULTS: The preferred
      adjuvant treatment shifted from fluorouracil, anthracycline and cyclophosphamide
      containing regimens to anthracycline/taxane combinations. Taxane use increased
      for all subtypes, and the greatest rise was among node-negative patients. Older
      age, node-negativity, lower grading, HR-positive/HER2-negative subtype and
      earlier start year of therapy were significantly associated with taxane-free
      therapy. CONCLUSIONS: Treatment with anthracycline/taxane-based chemotherapy in
      Germany has been rising for every subtype. The increased taxane use reflects
      updated guideline recommendations over the past decade. Cohort studies like the
      TMK provide insight into real-life treatment of patients outside of clinical
      trials.

PMID- 29204848
TI  - B-cell populations are expanded in breast cancer patients compared with healthy
      controls.
AB  - BACKGROUND: Historically, humoral immunity was considered unimportant in anti
      tumor immunity, and the differentiation and anti-tumor activity of B cells in
      breast cancer are poorly understood. However, it was recently discovered that B
      cells participate in tumor immunity through both antibody production and
      immunosuppressive mechanisms. We analyzed the expression of B-cell
      differentiation markers in detail using fluorescence-activated cell sorting to
      investigate the relationship between B-cell subsets and breast cancer etiology.
      METHODS: Blood samples were taken from breast cancer patients and healthy donors,
      and peripheral blood mononuclear cells were collected. B cells at various stages
      of differentiation were identified by the expression of combinations of the cell
      surface markers CD5, CD19, CD21, CD24, CD27, CD38, CD45, and IgD. Statistical
      analysis of the proportions of each B-cell subtype in the different patient
      groups was then performed. RESULTS: Twenty-seven breast cancer patients and 12
      controls were considered. The proportion of total B cells was significantly
      higher in cancer patients than in controls (11.51 +/- 2.059 vs 8.905 +/- 0.379%,
      respectively; p = 0.001). Breast cancer patients were then classified as High-B
      or Low-B for further analysis. A significantly higher proportion of memory B
      cells was found in the High-B group than in the Low-B or control groups (p =
      0.003 and p = 0.043, respectively). CONCLUSIONS: Breast cancer patients generally
      have a higher proportion of B cells than healthy controls, but this is highly
      variable. Analysis of the major B-cell surface markers indicates that memory B
      cells in particular are significantly expanded, or more robust, in breast cancer
      patients.

PMID- 29204849
TI  - Human intestinal spirochetosis mimicking ulcerative colitis.
AB  - Human intestinal spirochetosis (HIS) is a colorectal infection caused by the
      Brachyspira species of intestinal spirochetes, whose pathogenicity in humans
      remains unclear owing to the lack of or mild symptoms. We monitored the 5-year
      clinical course of a woman diagnosed with HIS in whom ulcerative colitis (UC) had
      been suspected. Following a positive fecal occult blood test, she underwent a
      colonoscopic examination at a local clinic where she was diagnosed with "right
      sided" UC concomitant with incidentally detected HIS, and was referred to our
      hospital. Colonoscopic, histopathological, and cytological examination revealed
      localized erosive colitis in the ascending and the right transverse colon
      concomitant with HIS resembling skip lesions of UC. Initially, we chose the wait
      and-watch approach; however, she gradually developed bloody diarrhea.
      Metronidazole improved her abdominal symptoms, as well as her colonoscopic and
      histopathological findings, suggesting that HIS was responsible for her
      colorectal inflammation. This case reveals (1) a possible pro-inflammatory role
      of HIS, (2) difficulties in diagnosing HIS in chronic proctocolitis, and (3) a
      possible inclusion of some HIS cases in "UC". HIS could mimic UC and might be
      included in differential diagnoses for UC. Antibiotic administration is necessary
      following the detection of HIS, particularly in patients demonstrating an
      atypical presentation of UC.

PMID- 29204850
TI  - Influence of blood pressure level and age on within-visit blood pressure
      variability in children and adolescents.
AB  - : Blood pressure (BP) is variable in children and this could affect BP
      assessment, but the magnitude of within-visit BP variability (BPV) over
      consecutive measurements has never been investigated. This study aimed to
      determine the direction and magnitude of, and factors affecting, within-visit BPV
      in children and adolescents. BP was recorded among 3047 children (aged 12 years
      [95%CI 12, 13], males 52%) from the 2011-2013 Australian Health Survey. BPV was
      defined as the absolute difference (?SBPABS) between the first (SBP1) and second
      systolic BP (SBP2) and the overall variability in three measures when available
      (SBPV). On average, ?SBPABS was 6.7 mmHg (95%CI 6.3, 7.0) and SBPV was 8.2%
      (95%CI 7.8, 8.6). ?SBPABS was greater with higher BP levels but lower with older
      age. From first to second measurements, SBP decreased in 58% (95%CI 56, 60), did
      not change in 10% (95%CI 9, 12), and increased in 32% (95%CI 29, 34) of the
      population. CONCLUSIONS: BP is highly variable in children and adolescents, with
      the magnitude of variability being associated with both age and BP level. SBP
      increases on repeat measurement in a substantial proportion of the population.
      The optimal protocol of BP assessment to address this increased BPV needs to be
      determined. What is Known: * Diagnosis of elevated blood pressure (BP) is based
      on strict probabilistic criteria, the difference between the 90th (pre
      hypertension) and 95th (hypertension) percentiles only being 3-4 mmHg. * BP
      variability could affect BP classification among children and adolescents. What
      is New: * The magnitude of BP change among children and adolescents is highly
      affected by BP level and age. * BP does not always drop on consecutive
      measurements, and evidence-based BP assessment protocols should be established to
      avoid misdiagnosis of hypertension.

PMID- 29204851
TI  - Fixed versus variable practice for teaching medical students the management of
      pediatric asthma exacerbations using simulation.
AB  - : Simulation-based trainings represent an interesting approach to teach medical
      students the management of pediatric asthma exacerbations (PAEs). In this study,
      we compared two pedagogical approaches, training students once on three different
      scenarios of PAEs versus training students three times on the same scenario of
      PAE. Eighty-five third-year medical students, novice learners for the management
      of PAEs, were randomized and trained. Students were assessed twice, 1 week and 4
      months after the training, on a scenario of PAE new to both groups and on
      scenarios used during the training. The main outcome was the performance score on
      the new scenario of PAE at 1 week, assessed on a checklist custom-designed for
      the study. All students progressed rapidly and acquired excellent skills. One
      week after the training, there was no difference between the two groups on all
      the scenarios tested, including the new scenario of PAE (median performance score
      (IQR) of 8.3 (7.4-10.0) in the variation group versus 8.0 (6.0-10.0) in the
      repetition group (p = 0.16)). Four months later, the performance of the two
      groups remained similar. CONCLUSION: Varying practice with different scenarios
      was equivalent to repetitive practice on the same scenario for novice learners,
      with both methods leading to transfer and long-term retention of the skills
      acquired during the training. What is known: * Simulation-based trainings
      represent an interesting approach to teach medical students the management of
      pediatric asthma exacerbations. * It is unclear whether students would benefit
      more from repetitive practice on the same scenario of asthma exacerbation or from
      practice on different scenarios in terms of transfer of skills. What is new: * An
      individual 30-min training on the management of pediatric asthma exacerbations
      using simulation allows transfer and long-term retention of the skills acquired.
      * Varying practice with different scenarios is equivalent to repetitive practice
      on the same scenario in terms of transfer of skills.

PMID- 29204852
TI  - European Antibiotic Awareness Day 2017: training the next generation of health
      care professionals in antibiotic stewardship.
AB  - : Antimicrobial stewardship (AMS) aims to optimise treatment, minimise the risk
      of adverse effects and reduce health care costs. In addition, it is recognised as
      a key component to stop the current spread of antimicrobial resistance in Europe.
      Educational programmes are particularly important for the successful
      implementation of AMS. Training should start during medical school, continue
      during clinical training and be reinforced throughout postgraduate training.
      National core curricula for paediatric training should include passive and active
      training of competencies needed for AMS and future paediatricians should be
      skilled in taking leadership roles in AMS initiatives. Other core members of the
      paediatric AMS team should also receive training focused on the unique medical
      needs of the paediatric patient. CONCLUSION: Ideally, all communities, hospitals
      and health regions in Europe should have AMS that serve all patient types,
      including children. We all have the responsibility to ensure that existing
      antibiotics remain effective. What is Known: * Antimicrobial stewardship (AMS) is
      a key component to stop the current spread of antimicrobial resistance *
      Educational programmes are particularly important for the successful
      implementation of AMS What is New: * All medical doctors in Europe who will be
      undertaking significant practice in child health should master the competencies
      needed to prescribe antibiotics to children rationally as described in the
      European Academy of Paediatrics (EAP) Curriculum for Common Trunk Training in
      Paediatrics * Interdisciplinary approaches of education need to be developed, as
      all hospitals and health regions in Europe ideally should have AMS programmes
      that serve all patient types, including children.

PMID- 29204854
TI  - Nuclear cardiology in the literature: A selection of recent, original research
      papers.

PMID- 29204853
TI  - Health indicators and social gradient in adolescent immigrants' health risk and
      healthcare experiences.
AB  - : Few studies have assessed healthcare experiences in apparently healthy
      adolescents, or whether healthcare attitudes are linked to the two leading
      adolescent health indicators, smoking and obesity. Even fewer have examined these
      relationships in adolescent immigrant groups or made comparisons to adolescent
      non-immigrants. Using a cross-sectional study, healthcare experiences were
      compared among three groups of adolescents (n = 589) including Russian immigrants
      (n = 154), Ethiopian immigrants (n = 54), and non-immigrants (n = 381). Bootstrap
      estimates indicated positive healthcare experiences were less common among
      Russian adolescent immigrants (OR = 0.38, CI = 0.17, 0.86) compared to non
      immigrants, unless the Russian adolescent immigrants reported above average
      socioeconomic status, in which case they were more likely than non-immigrant
      adolescents to report positive healthcare experiences (OR = 3.22, CI = 1.05,
      9.85). Positive healthcare experiences were less likely among adolescents who
      were smokers (OR = 0.50, CI = 0.27, 0.91), and more likely for adolescents with a
      normal or low BMI (OR = 3.16, CI = 1.56, 6.40) and for those relying on parents
      for health information (OR = 1.97, CI = 1.05, 3.70). CONCLUSION: Findings suggest
      a social gradient in which positive healthcare experiences were more common among
      adolescence with higher socioeconomic status for some immigrants (Russian
      adolescents) but not for others. The two leading health indicators were related
      to healthcare experiences, but as adolescent smokers were less likely to have
      positive healthcare experiences, proactive efforts are needed to engage this
      group. What is Known: * Health indicators (such as obesity) and healthcare
      attitudes are linked to healthcare service use among adolescents sampled from
      outpatient and inpatient populations. What is New: * A social gradient involving
      socioeconomic status and being an adolescent immigrant was found regarding risky
      health indicators (i.e., smoking, use of internet as the primary source of health
      information). * Problematic health indicators, such as smoking, is linked to less
      positive healthcare attitudes in apparently healthy adolescents (both immigrants
      and non-immigrants).

PMID- 29204856
TI  - ?

PMID- 29204857
TI  - ?

PMID- 29204855
TI  - Achieving Good Glycemic Control Early After Onset of Diabetes: A Cost
      Effectiveness Analysis in Patients with Type 1 Diabetes in Sweden.
AB  - INTRODUCTION: Sweden has amongst the highest incidence rates of type 1 diabetes
      (T1D) in Europe. The high incidence and chronic nature of T1D result in high
      prevalence and economic burden. Improving glycemic control reduces the incidence
      of microvascular complications, which in turn reduces medical costs. The present
      study aimed to quantify the reductions in cost and improvements in quality
      adjusted life expectancy with varying reductions in HbA1c in the T1D population.
      METHODS: The IQVIA CORE Diabetes Model was used to simulate a typical Swedish
      population of patients with T1D experiencing HbA1c reductions from 0.1% to 0.8%
      (in 0.1% increments) from 7.9% at baseline. Analyses were conducted in simulated
      cohorts based on data from the Swedish National Diabetes Register (NDR) and in
      subgroups by sex, smoking status, and body mass index (BMI), with different sets
      of quality-of-life utilities included. Generalized least squares (GLS) models
      were used to test for significant differences between subgroups. Analyses were
      also performed to investigate the effect of the duration of HbA1c control.
      Analyses were run over 50 years and outcomes discounted at 3% per annum. RESULTS:
      In the reference case analysis, reducing HbA1c lowered the incidence of
      microvascular and macrovascular complications and improved quality-adjusted life
      expectancy. GLS models identified a significantly larger benefit of reducing
      HbA1c in women over men, but found no significant differences in the magnitude of
      quality of life improvements with decreasing HbA1c when segregating by smoking
      status or BMI. CONCLUSIONS: Reducing HbA1c in a population with T1D would reduce
      the incidence of microvascular complications, improve life expectancy and quality
      of life. Larger quality-of-life benefits were observed in younger and female
      adult patients, but no notable differences were observed in the benefits of
      glycemic control in smokers versus non-smokers or in patients with low or high
      BMI. FUNDING: Novo Nordisk Scandinavia AB, Malmo, Sweden.

PMID- 29204858
TI  - A Retrospective Analysis of Corticosteroid Utilization Before Initiation of
      Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.
AB  - INTRODUCTION: Understanding the effects of corticosteroid utilization prior to
      initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform
      decision-makers on the appropriate use of these medications. This study examined
      treatment patterns and associated burden of corticosteroid utilization before
      initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. METHODS:
      A retrospective analysis was conducted of adult RA patients in the US MarketScan
      Database (2011-2015). The following patterns of corticosteroid utilization were
      analyzed: whether corticosteroids were used; duration of use (short/long duration
      defined as < or >= 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5
      and high as >= 7.5 mg/day). Effects of corticosteroid use on time to biologic
      DMARD initiation were examined using Cox proportional hazards models. Likelihood
      and number of adverse events were examined using logistic and negative binomial
      regression models. Generalized linear models were used to examine healthcare
      costs. Independent variables in all models included patient demographics and
      health characteristics. RESULTS: A total of 25,542 patients were included (40.84%
      used corticosteroids). Lower hazard of biologic DMARD initiation was associated
      with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83
      0.96), long duration and lower dose. Corticosteroid users compared to non-users
      had higher incidence rates of various adverse events including cardiovascular
      events (P < 0.05). Higher likelihood of adverse events was associated with
      corticosteroid use and long duration of use, as was increased number of adverse
      events. Corticosteroid users had a greater annualized mean number of physician
      visits, hospitalizations, and emergency department (ED) visits than non-users in
      adjusted analysis. Corticosteroid users compared to non-users had higher mean
      costs for total healthcare, physician visits, hospitalizations, and ED visits.
      CONCLUSIONS: Among patients with RA, corticosteroid utilization is associated
      with delayed initiation of biologic DMARDS and higher burden of adverse events
      and healthcare utilization/costs before the initiation of biologic DMARDs.
      FUNDING: AbbVie Inc.

PMID- 29204859
TI  - Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout:
      Results from the GEMA-2 Transversal Study on Practice.
AB  - INTRODUCTION: The objective of the study was to evaluate changes regarding main
      European League Against Rheumatism (EULAR) recommendations on diagnosis and
      treatment of gout compared to a previous assessment. METHODS: The GEMA-2 (Gout
      Evaluation and MAnagement) is a transversal assessment of practice for gout by
      rheumatologists. Main outcome variables were improvement of the previous GEMA
      assessment regarding the rate of crystal-proven diagnosis and that reaching
      therapeutic serum urate target below 6 mg/dl at last visit. Other management
      variables (prophylaxis, treatment of flares, lifestyle change advice) were also
      evaluated along with general characteristics. The sample was powered to include
      at least 483 patients for up to 50% change. RESULTS: Data on management of 506
      patients were retrieved from 38 out of 41 rheumatology units that participated in
      the previous GEMA audit. Crystal-proved diagnosis rate increased from 26% to 32%
      (31% improvement) and was higher in gout-dedicated practices; ultrasonography
      contributed to diagnosis in less than 1% of cases. Therapeutic serum urate at
      last visit improved from 41% to 64% of all patients (66% of patients on urate
      lowering medications), in any case over 50% improvement from the previous
      assessment. The use of any urate-lowering medication available was not prescribed
      as per label dosing in patients who failed to achieve target serum urate.
      Clinical inertia to increase doses of either allopurinol or febuxostat was still
      present in clinical practice. CONCLUSION: Over 50% improvement in targeting
      therapeutic serum urate has been observed, but clinical inertia is still present.
      Diagnosis is still mostly clinically based, ultrasonography not being commonly
      contributive. FUNDING: Menarini Espana.

PMID- 29204860
TI  - DEC1 is required for anti-apoptotic activity of gastric cancer cells under
      hypoxia by promoting Survivin expression.
AB  - BACKGROUND: Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1),
      which has been reported to be overexpressed in several types of cancer, is
      associated with tumorigenesis through participation in several biological
      processes. However, the complex mechanisms underlying DEC1 during carcinogenesis
      are controversial, and its roles in the development and malignancy of gastric
      cancer (GC) remain unclear. METHODS: We measured DEC1 expression in human GC cell
      lines. DEC1 levels in GC cells were downregulated by shRNA lentivirus infection.
      We also evaluated the effect of DEC1 downregulation on xenograft growth in vivo.
      The viability and apoptosis of the cells were assayed using the CCK8 assay and
      flow cytometry. The levels of DEC1, Survivin, and Bcl-2 were evaluated by Western
      blotting. Luciferase reporter was used to verify the downstream target of DEC1.
      The association of DEC1 and Survivin expression with prognosis was investigated
      by immunohistochemistry. RESULTS: Downregulation of DEC1 inhibits GC cell
      proliferation in vitro and tumorigenicity in vivo. We observed that hypoxia
      induced expression of DEC1 protects GC cells from apoptosis via transcriptional
      upregulation of Survivin. Furthermore, positive correlations between DEC1 with
      Survivin expression were observed in tissue sections from GC patients. Notably,
      GC patients with high expression levels of DEC1 and Survivin showed poor
      prognosis. CONCLUSIONS: DEC1 acts as an anti-apoptotic regulator in GC cells
      under hypoxia by promoting Survivin expression. Our study demonstrates the
      critical role of the DEC1 in oncogenesis and highlights a novel role for DEC1 in
      the regulation of cell apoptosis in GC.

PMID- 29204861
TI  - Kinematically aligned total knee arthroplasty reduces knee adduction moment more
      than mechanically aligned total knee arthroplasty.
AB  - PURPOSE: Knee adduction moment (KAM) has been recognized as a good clinical
      surrogate for medial tibiofemoral joint loading and is associated with implant
      durability after total knee arthroplasty (TKA). This study aimed to examine the
      effects of joint line obliquity in kinematically aligned TKA (KA-TKA) on KAM
      during gait. METHODS: The study enrolled 21 knees from 18 patients who underwent
      cylindrical axis reference KA-TKA and a matched group of 21 knees from 18
      patients who underwent mechanically aligned (MA)-TKA as controls. Gait analyses
      were performed the day before TKA and at an overall mean of 2.6 years
      postoperatively. First peak KAM and variables associated with frontal knee
      kinetics were determined and compared between groups. RESULTS: In KA-TKA, the
      proximal tibia was resected with 3.4 degrees  +/- 1.5 degrees  of varus in
      relation to the mechanical axis, and the final femorotibial shaft axis was 176.7
      degrees  +/- 3.8 degrees  with KA-TKA and 174.4 degrees  +/- 3.0 degrees  with MA
      TKA. KAM was significantly smaller with KA-TKA than with MA-TKA (p < 0.032).
      Regarding variables affecting KAM, significant differences were evident between
      the two TKAs for knee adduction angle (p = 0.0021), lever arm (p = 0.028), and
      Deltalever arm (p = 0.0001). CONCLUSIONS: In KA-TKA, joint line obliquity reduced
      peak KAM during gait, despite slight varus limb alignment, and this reduced KAM
      in KA-TKA can tolerate constitutional varus alignment. In clinical settings, KA
      TKA thus represents a promising technical option for patients with large coronal
      bowing of the shaft carrying a risk of increased KAM after TKA. LEVEL OF
      EVIDENCE: III.

PMID- 29204862
TI  - The trochlear isometric point is different in patients with recurrent patellar
      instability compared to controls: a radiographical study.
AB  - PURPOSE: The purpose of the study was to investigate the theoretical isometric
      point based of the curve of the femoral groove and relating it to the origin of
      the MPFL femoral tunnel on lateral radiograph by comparing a patellar instability
      cohort with a control cohort. METHODS: From a Patellar Instability database the
      radiographs of 40 consecutive patients were analysed to define Schottle's point,
      and the arc of the circle of the trochlear groove. A comparison population of 20
      radiographs from comparable patients with tibiofemoral joint disorders was used
      as a control. The distance from Schottle's point to the most anterior part of the
      groove (extension) was also compared to the distance to the distal end of the
      roof of the notch (flexion). RESULTS: The trochlea was circular in the controls
      but not the Patellofemoral Instability cohort where trochlear dysplasia is
      usually present. The difference between the extension and flexion length was a
      mean of - 2.0 +/- 0.5 mm in the controls and + 6.0 +/- 0.5 mm in the
      patellofemoral cohort. In neither cohort did the centre of the circle correspond
      to Schottle's point. The extension distance correlated with the boss height.
      CONCLUSIONS: The dysplastic trochlea is not circular and the centre of the best
      matched circle was different to the control trochleae which were circular. The
      circle centres did not correlate with Schottle's point for either cohort, and was
      more proximal in the Patellofemoral Instability cohort. CLINICAL RELEVANCE: For
      the MPFL to have equal tension throughout flexion within the groove, the length
      should not change. In normal knees the MPFL does not behave isometrically. The
      change in length, as measured from Schottle's point to the trochlea, was greater
      for patellofemoral instability patients explaining why an isolated MPFL
      reconstruction in the presence of severe trochlear dysplasia risks poor outcomes.
      Level of evidence III.

PMID- 29204864
TI  - ERP evidence for temporal independence of set size and object updating in object
      substitution masking.
AB  - To keep track of dynamically changing objects in one's environment, it is
      necessary to individuate them from other objects, both temporally and spatially.
      Spatially, objects can be selected from nearby distractors using selective
      attention. Temporally, object updating processes incorporate new information into
      existing representations over time. Both of these processes have been implicated
      in a type of visual masking called object-substitution masking (OSM). Previous
      studies have found that the number of distractors (impacting selective attention)
      interacts with the strength of OSM. However, it has been suggested that this
      interaction is an artifact of ceiling performance at low set sizes, rather than
      necessitating a failure of attention during masking. Using event-related
      potentials (ERPs), we examined whether set size and masking interact as measured
      by markers of selective attention (N2pc) and visual working memory
      consolidation/maintenance (SPCN). Set size was found to affect the N2pc (200-350
      ms) and late SPCN (500-650 ms), reflecting increased demands on selective
      attention and unnecessary storage respectively. An early window of the SPCN (350
      500 ms) was affected by masking, suggesting that OSM influences object
      consolidation processes in this window, independent of the number of distractors.
      Overall, it was found that selective attention and visual awareness are
      dissociable neural processes in OSM, and that they are independently affected by
      set size and masking manipulations. Moreover, we found that the early SPCN may
      reflect disruptions to object consolidation, potentially revealing a neural
      mechanism supporting an object individuation-through-updating account of OSM.

PMID- 29204863
TI  - No difference in prevalence of spine and hip pain in young Elite skiers.
AB  - PURPOSE: To investigate the prevalence between back and hip pain in young Elite
      skiers. METHODS: Sample group (n = 102), consisted of young Elite skiers (n = 75)
      and age-matched non-athletes (n = 27), all completed a three-part back and hip
      pain questionnaire, Oswestry Disability Index and EuroQoL to evaluate general
      health, activity level, back and hip pain prevalence. RESULTS: No significant
      differences were shown for lifetime prevalence of back pain in the skiers (50%)
      compared with controls (44%) (n.s.). Duration of back pain for the skiers showed
      (30%) > 1 year, whilst (46%) > 5 years. A significant difference was shown with
      increased Visual Analogue Scale back pain levels for skiers 5.3 (SD 3.1) compared
      with controls 2.4 (SD 1.9, p = 0.025). No significant differences were shown for
      lifetime prevalence of hip pain in skiers (21%) compared with controls (8%)
      (n.s.). CONCLUSION: Young Elite skiers are shown not to have increased lifetime
      prevalence for back and hip pain compared with a non-athletic control group.
      LEVEL OF EVIDENCE: II.

PMID- 29204865
TI  - The role of top-down knowledge about environmental context in egocentric distance
      judgments.
AB  - Judgments of egocentric distances in well-lit natural environments can differ
      substantially in indoor versus outdoor contexts. Visual cues (e.g., linear
      perspective, texture gradients) no doubt play a strong role in context-dependent
      judgments when cues are abundant. Here we investigated a possible top-down
      influence on distance judgments that might play a unique role under conditions of
      perceptual uncertainty: assumptions or knowledge that one is indoors or outdoors.
      We presented targets in a large outdoor field and in an indoor classroom. To
      control visual distance and depth cues between the environments, we restricted
      the field of view by using a 14-deg aperture. Evidence of context effects
      depended on the response mode: Blindfolded-walking responses were systematically
      shorter indoors than outdoors, whereas verbal and size gesture judgments showed
      no context effects. These results suggest that top-down knowledge about the
      environmental context does not strongly influence visually perceived egocentric
      distance. However, this knowledge can operate as an output-level bias, such that
      blindfolded-walking responses are shorter when observers' top-down knowledge
      indicates that they are indoors and when the size of the room is uncertain.

PMID- 29204866
TI  - Tracking working memory maintenance with pupillometry.
AB  - Phasic pupillary responses were used to track the active maintenance of
      information in working memory (WM). In seven experiments participants performed
      various change detection tasks while their pupils were continuously recorded.
      Across the experiments phasic pupillary responses increased as the number of
      maintained items increased up to around 4-5 items consistent with behavioral
      estimates of capacity. Combining data across experiments demonstrated that phasic
      pupillary responses were related to behavioral estimates of capacity.
      Furthermore, phasic pupillary responses demonstrated WM load-dependent relations
      only when active maintenance was required. When instructed to passively stare at
      the items or to drop items from WM, the pupil remained near baseline levels.
      These phasic pupillary responses also tracked the time course of maintenance
      demonstrating sustained responses early in the delay period, but declined
      thereafter. Finally, phasic pupillary responses tracked selection processes at
      encoding (filtering and pre-cues), but did not suggest evidence for item removal
      following retro-cues. These results are consistent with the notion that
      maintaining items in WM requires the allocation of effortful attention and
      further suggest that phasic pupillary responses can be used to track the active
      maintenance of items in WM.

PMID- 29204867
TI  - Talking heads or talking eyes? Effects of head orientation and sudden onset gaze
      cues on attention capture.
AB  - The direction of gaze towards or away from an observer has immediate effects on
      attentional processing in the observer. Previous research indicates that faces
      with direct gaze are processed more efficiently than faces with averted gaze. We
      recently reported additional processing advantages for faces that suddenly adopt
      direct gaze (abruptly shift from averted to direct gaze) relative to static
      direct gaze (always in direct gaze), sudden averted gaze (abruptly shift from
      direct to averted gaze), and static averted gaze (always in averted gaze).
      Because changes in gaze orientation in previous study co-occurred with changes in
      head orientation, it was not clear if the effect is contingent on face or eye
      processing, or whether it requires both the eyes and the face to provide
      consistent information. The present study delineates the impact of head
      orientation, sudden onset motion cues, and gaze cues. Participants completed a
      target-detection task in which head position remained in a static averted or
      direct orientation while sudden onset motion and eye gaze cues were manipulated
      within each trial. The results indicate a sudden direct gaze advantage that
      resulted from the additive role of motion and gaze cues. Interestingly, the
      orientation of the face towards or away from the observer did not influence the
      sudden direct gaze effect, suggesting that eye gaze cues, not face orientation
      cues, are critical for the sudden direct gaze effect.

PMID- 29204868
TI  - Increased live births after day 5 versus day 6 transfers of vitrified-warmed
      blastocysts.
AB  - PURPOSE: An investigation into the clinical implications of delayed blastulation
      (day 5 versus day 6) was carried out for cryo cycles, as heterogeneous results
      persist in the current literature. METHODS: We performed a retrospective study
      comparing clinical pregnancies and live births between 178 blastocysts vitrified
      and warmed on day 5 versus 149 on day 6. The stage of blastocyst development was
      taken into account and adjustment for confounding factors was performed. RESULTS:
      Our results demonstrate a significant difference in clinical pregnancy (43 versus
      23% p value < 0.001) and live birth rates (34 versus 16% p value < 0.001)
      regarding the day of vitrification, in favour of day 5. This difference persisted
      after adjustment for confounding factors. The adjusted odds ratio for clinical
      pregnancies and deliveries for the day 5 group compared to that of the day 6
      group was 2.83 (95%CI, 1.48 to 5.41) and 2.94 (95%CI, 1.39 to 6.22),
      respectively. When the stage of development of the blastocyst was taken into
      consideration, we still observed a significant advantage of day 5 versus day 6
      vitrification. CONCLUSIONS: Day of vitrification (day 5 versus day 6) appears to
      be an independent predictor of clinical outcomes. Stratification of our cohort
      was carried out according to the developmental stage, and significant differences
      persisted. Although the transfer of day 6 cryopreserved embryos remains a viable
      option, giving priority to a day 5 embryo would reduce the time to pregnancy.

PMID- 29204870
TI  - Correction to: Age estimation based on pelvic ossification using regression
      models from conventional radiography.
AB  - The original version of this article unfortunately contained a mistake in the
      Results section. The correct equation from the cubic regression analysis for male
      is: Age = 14.408 + 0.475X-0.064X2 + 0.005X3, and for the female is: 18.196-1.637X
      + 0.204X2-0.005X3. The error doesn't affect the main conclusion.

PMID- 29204869
TI  - Estrogen treatment in infertile women with premature ovarian insufficiency in
      transitional phase: a retrospective analysis.
AB  - PURPOSE: During the transitional phase of premature ovarian insufficiency (POI),
      sporadic resumption of ovulation is possible because of fluctuation of hormonal
      levels but the chance of spontaneous pregnancy is low, and the main perspective
      of childbearing in these women is egg donation or adoption. The purpose of the
      study was to verify whether treatment with estrogens in POI patients in
      transitional phase could reduce FSH levels and to evaluate if this pre-treatment
      could improve reproductive outcomes of in vitro fertilization (IVF). METHODS:
      Study patients (26) were administered with valerate estradiol 2 mg daily adding
      dihydrogesterone 10 mg daily during luteal phase for 3 months before IVF. Control
      group (26 patients) did not receive any pre-treatment. Ovarian stimulation was
      conducted in both groups with the same short GnRH-antagonist protocol. Clinical
      and laboratory data of patients were retrospectively analyzed. RESULTS: In the
      study group, 4/26 POI patients became spontaneously pregnant during pre
      treatment. In the remaining patients, the mean level of FSH after the pre
      treatment was significantly reduced compared with baseline. Levels of circulating
      estradiol on the day of hCG administration were significantly higher in the study
      group. The total number of MII oocytes retrieved and fertilized oocytes was
      significantly higher in the study group, as well as the number of embryos
      transferred for pickup and clinical pregnancy rate. CONCLUSIONS: Treatment with
      estrogens in infertile POI patients in transitional phase reduces circulating FSH
      levels, hence causing potential spontaneous conception. Moreover, in these
      patients, estrogen pre-treatment seems to improve IVF outcomes in a GnRH
      antagonist short protocol compared to no pre-treatment.

PMID- 29204871
TI  - Bone Marrow Mesenchymal Stem Cells Combat Lipopolysaccharide-Induced Sepsis in
      Rats via Amendment of P38-MAPK Signaling Cascade.
AB  - Sepsis is a systemic inflammatory disorder which often occurs during extremely
      stressful conditions such as trauma, burn, shock, and infection. This study
      investigated the curative effects of bone marrow-derived mesenchymal stem cells
      (BM-MSCs) against hepatic, renal, and pulmonary responses caused by a single
      administration of lipopolysaccharide (LPS) (10 mg/kg, i.p) in rats. Treatment
      with BM-MSCs (5 * 105 in 0.1 ml PBS, i.p.) 3 h after LPS antagonized the LPS
      induced increment of the liver enzymes (ALT, AST) and kidney functions (BUN,
      sCr). BM-MSCs decreased tissue levels of P38-MAPK, NF-kappaB, STAT-3, TNF-alpha,
      IL-1beta, iNOS, Bax together with elevation of the anti-inflammatory cytokine IL
      10 and the anti-apoptotic biomarker Bcl-2. Meanwhile, rats exhibited marked
      reduction of the broncho-alveolar lavage fluid levels of TNF-alpha, IL-1beta, and
      IFN-gamma. Interestingly, BM-MSCs normalized both broncho-alveolar lavage fluid
      (BALF) neutrophils count and lung wet/dry ratios. Briefly, these findings may
      provide a preclinical platform for the management of LPS-induced sepsis using BM
      MSCs via their ameliorative anti-inflammatory, anti-oxidant, and anti-apoptotic
      potentials.

PMID- 29204873
TI  - Abstracts 2017.

PMID- 29204874
TI  - Continuing education: from FRCPC to ACGME fellowship.

PMID- 29204872
TI  - Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced
      Mastitis in Mice.
AB  - Rosmarinic acid (RA), a type of food additives mainly extracted from rosemary,
      has been reported to possess anti-inflammatory activities in some previous
      studies. However, the effects of RA on lipopolysaccharide (LPS)-induced mastitis
      have not been reported. Here, we investigated the anti-inflammatory effects of RA
      on LPS-induced mastitis in mice and elucidated the potential mechanisms in mouse
      mammary epithelial cells (mMECs). RA treatment significantly ameliorated the
      mammary structural damage, and reduced the activity of myeloperoxidase. ELISA and
      qPCR results indicated that RA dose-dependently decreased the expression of TNF
      alpha, IL-1beta, and IL-6 both in tissues and mMECs. Furthermore, RA remarkably
      suppressed the protein levels of TLR4, MyD88, IRAK1, TRAF6, and p-IKKbeta. In
      addition, RA was also found to inhibit LPS-induced NF-kappaB signaling pathway
      activation. These results suggest that RA effectively attenuates LPS-induced
      mastitis by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway.

PMID- 29204875
TI  - Focused assessment with sonography in trauma: a review of concepts and
      considerations for anesthesiology.
AB  - The use of point-of-care ultrasound in trauma provides diagnostic clarity and
      routinely influences management. A scanning protocol known as the Focused
      Assessment with Sonography in Trauma (FAST) has been widely adopted by trauma
      providers of all specialties. The FAST exam addresses a broad array of pathologic
      conditions capable of causing instability, including hemoperitoneum,
      hemopericardium, hemothorax, and pneumothorax. The exam is an integral component
      to the primary assessment of injured patients and an iconic application of point
      of-care ultrasound.This review article aims to summarize the application of the
      FAST exam with special consideration, where relevant, to anesthesiologists. The
      scope of the FAST exam, technical considerations, and clinical decision-making in
      trauma are explored.

PMID- 29204876
TI  - High intraoperative endotracheal tube cuff pressure incidence and clinical
      impact.

PMID- 29204877
TI  - How multi-scale structural biology elucidated context-dependent variability in
      ectodomain conformation along with the ligand capture and release cycle for LDLR
      family members.
AB  - The low-density lipoprotein receptor (LDLR) and its homologs capture and
      internalize lipoproteins into the cell. Due to the fact that LDLR family members
      possess a modular ectodomain that undergoes dynamic conformational changes, multi
      scale structural analysis has been performed so as to understand the ligand
      capture and release mechanism. For example, crystallographic analyses have
      provided models for both the entire ectodomain and high-resolution structures of
      individual modules. In addition, nuclear magnetic resonance spectroscopic
      analyses have shown the rigidity and flexibility of inter-module linkers to
      restrict the mobility of ectodomain. Accumulated structural data suggest that the
      ectodomains of LDLR family members are flexible at the cell surface and switch
      between two metastable conformations, that is, the extended and contracted
      conformations. Recent structural analysis of ApoER2, a close homolog of LDLR,
      raised the possibility that the receptor binds with the ligand in the contracted
      conformation. After transport to an endosome by endocytosis, the receptor
      undergoes a conformational change to the closed conformation for completion of
      ligand release. In contrast, LDLR has been reported to adopt the extended
      conformation when it binds with a inhibitory regulator that recruits LDLR toward
      the degradation pathway. These findings support a mechanism of different
      ectodomain conformations for binding the ligand versus binding the regulatory
      protein. In this review, I provide an overview of studies that analyze the
      structural and biophysical properties of the ectodomains of LDLR family members
      and discuss a hypothetical model for ligand uptake and receptor recycling that
      integrates the known ectodomain conformational variability.

PMID- 29204878
TI  - Gliadins from wheat grain: an overview, from primary structure to nanostructures
      of aggregates.
AB  - Gliadins are well-known wheat grain proteins, particularly important in food
      science. They were studied as early as the 1700s. Despite their long history, it
      has been difficult to identify their higher-order structure as they aggregate in
      aqueous solution. Consequently, most studies have been performed by extracting
      the proteins in 70% ethanol or dilute acidic solutions. The carboxy-terminal half
      of alpha- and gamma-gliadins have alpha-helix-rich secondary structures
      stabilized with intramolecular disulfide bonds, which are present in either
      aqueous ethanol or pure water. The amino-terminal-repeat region of alpha- and
      gamma-gliadins has poly-L-proline II and beta-reverse-turn structures. omega
      Gliadins also have poly-L-proline II and beta-reverse-turn structures, but no
      alpha-helix structure. The size and shape of gliadin molecules have been
      determined by assessing a variety of parameters: their sedimentation velocity in
      the analytical ultracentrifuge, intrinsic viscosity, small-angle X-ray scattering
      profile, and images of the proteins from scanning probe microscopes such as a
      tunneling electron microscope and atomic force microscope. Models for gliadins
      are either rods or prolate ellipsoids whether in aqueous ethanol, dilute acid, or
      pure water. Recently, gliadins have been shown to be soluble in pure water, and a
      novel extraction method into pure water has been established. This has made it
      possible to analyze gliadins in pure water at neutral pH, and permitted the
      characterization of hydrated gliadins. They formed hierarchical nanoscale
      structures with internal density fluctuations at high protein concentrations.

PMID- 29204879
TI  - Reconstitution of membrane tethering mediated by Rab-family small GTPases.
AB  - Membrane tethering is one of the most critical steps to determine the
      spatiotemporal specificity of membrane trafficking, which is the process to
      selectively transport proteins, lipids, and other biological molecules to the
      appropriate locations in eukaryotic cells, such as subcellular organelles, the
      plasma membrane, and the extracellular space. Based on genetic, cell biological,
      biochemical, and structural studies, Rab-family small GTPases and a number of Rab
      interacting proteins (termed Rab effectors), including coiled-coil tethering
      proteins and multisubunit tethering complexes, have been proposed to be key
      protein components for membrane tethering. Nevertheless, indeed whether and how
      Rab GTPases and their specific Rab effectors directly act upon and catalyze
      membrane tethering still remains enigmatic. By chemically defined reconstitution
      of membrane tethering from purified Rab-family GTPase proteins and synthetic
      liposomal membranes, recent studies have revealed the intrinsic potency of Rab
      family GTPases to physically and specifically tether two distinct lipid bilayers
      of liposomal membranes. Experimental evidence from these reconstitution studies
      support the novel working model in which Rab-family small GTPases act as a bona
      fide membrane tether for mediating membrane tethering events in eukaryotic
      membrane trafficking.

PMID- 29204880
TI  - Formation and properties of amyloid fibrils of prion protein.
AB  - Amyloid fibrils formed from prion protein (PrP) are associated with prion
      diseases. In this review we discuss a number of extrinsic and intrinsic
      experimental factors related to the formation of PrP amyloid fibrils in vitro. We
      first examined the effects of ultrasonic power on the induction of amyloid
      fibrillation from PrP. The most important conclusion drawn from the results is
      that an applied ultrasonic power of approximately 2 W enhanced the nucleation of
      amyloid fibrils efficiently but that more powerful ultrasonication led to
      retardation of growth. We also reviewed evidence on the amyloidogenic regions of
      PrP based on peptide screening throughout the polypeptide sequence. These results
      showed that helix 2 (H2) peptides of PrP were capable of both the fibrillation
      and propagation of straight, long fibrils. Moreover, the conformation of
      preformed H2 fibrils changed reversibly depending on the pH of the solution,
      implying that interactions between side-chains modulated the conformation of
      amyloid fibrils. The evidence discussed in this review relates specifically to
      PrP but may be relevant to other amyloidogenic proteins.

PMID- 29204881
TI  - Environment-transformable sequence-structure relationship: a general mechanism
      for proteotoxicity.
AB  - In his Nobel Lecture, Anfinsen stated "the native conformation is determined by
      the totality of interatomic interactions and hence by the amino acid sequence, in
      a given environment." As aqueous solutions and membrane systems co-exist in
      cells, proteins are classified into membrane and non-membrane proteins, but
      whether one can transform one into the other remains unknown. Intriguingly, many
      well-folded non-membrane proteins are converted into "insoluble" and toxic forms
      by aging- or disease-associated factors, but the underlying mechanisms remain
      elusive. In 2005, we discovered a previously unknown regime of proteins seemingly
      inconsistent with the classic "Salting-in" dogma: "insoluble" proteins including
      the integral membrane fragments could be solubilized in the ion-minimized water.
      We have thus successfully studied "insoluble" forms of ALS-causing P56S-MSP,
      L126Z-SOD1, nascent SOD1 and C71G-Profilin1, as well as E. coli S1 fragments. The
      results revealed that these "insoluble" forms are either unfolded or co-exist
      with their unfolded states. Most unexpectedly, these unfolded states acquire a
      novel capacity of interacting with membranes energetically driven by the
      formation of helices/loops over amphiphilic/hydrophobic regions which universally
      exit in proteins but are normally locked away in their folded native states. Our
      studies suggest that most, if not all, proteins contain segments which have the
      dual ability to fold into distinctive structures in aqueous and membrane
      environments. The abnormal membrane interaction might initiate disease and/or
      aging processes; and its further coupling with protein aggregation could result
      in radical proteotoxicity by forming inclusions composed of damaged membranous
      organelles and protein aggregates. Therefore, environment-transformable sequence
      structure relationship may represent a general mechanism for proteotoxicity.

PMID- 29204882
TI  - Multiscale molecular dynamics simulations of rotary motor proteins.
AB  - Protein functions require specific structures frequently coupled with
      conformational changes. The scale of the structural dynamics of proteins spans
      from the atomic to the molecular level. Theoretically, all-atom molecular
      dynamics (MD) simulation is a powerful tool to investigate protein dynamics
      because the MD simulation is capable of capturing conformational changes obeying
      the intrinsically structural features. However, to study long-timescale dynamics,
      efficient sampling techniques and coarse-grained (CG) approaches coupled with all
      atom MD simulations, termed multiscale MD simulations, are required to overcome
      the timescale limitation in all-atom MD simulations. Here, we review two examples
      of rotary motor proteins examined using free energy landscape (FEL) analysis and
      CG-MD simulations. In the FEL analysis, FEL is calculated as a function of
      reaction coordinates, and the long-timescale dynamics corresponding to
      conformational changes is described as transitions on the FEL surface. Another
      approach is the utilization of the CG model, in which the CG parameters are tuned
      using the fluctuation matching methodology with all-atom MD simulations. The long
      timespan dynamics is then elucidated straightforwardly by using CG-MD
      simulations.

PMID- 29204883
TI  - Multiple analyses of protein dynamics in solution.
AB  - The need for accurate description of protein behavior in solution has gained
      importance in various fields, including biophysics, biochemistry, structural
      biology, drug discovery, and antibody drugs. To achieve the desired accuracy,
      multiple precise analyses should be performed on the target molecule, compared,
      and effectively combined. This review focuses on the combination of multiple
      analyses in solution: size-exclusion chromatography (SEC), multi-angle light
      scattering (MALS), small-angle X-ray scattering (SAXS), analytical
      ultracentrifugation (AUC), and their complementary methods, such as atomic force
      microscopy (AFM) and mass spectrometry (MS). We also discuss the comparison
      between the determined molar mass value of not only the standard proteins, but of
      a target molecule tubulin and its depolymerizing protein, KIF2, as an example.
      The comparison of the estimated molar mass value from the different methods
      provides additional information about the target molecule, because the value
      reflects the dynamically changing states of the target molecule in solution. The
      combination and integration of multiple methods will permit a deeper
      understanding of protein dynamics in solution.

PMID- 29204885
TI  - Bacteriophage T4 long tail fiber domains.
AB  - Bacteriophage T4 initially recognizes its host cells using its long tail fibers.
      Long tail fibers consist of a phage-proximal and a phage-distal rod, each around
      80 nm long and attached to each other at a slight angle. The phage-proximal rod
      is formed by a homo-trimer of gene product 34 (gp34) and is attached to the phage
      distal rod by a monomer of gp35. The phage-distal rod consists of two protein
      trimers: a trimer of gp36, attached to gp35, although most of the phage-distal
      rod, including the receptor-binding domain, is formed by a trimer of gp37. In
      this review, we discuss what is known about the detailed structure and function
      of the different long tail fiber domains. Partial crystal structures of gp34 and
      gp37 have revealed the presence of new protein folds, some of which are present
      in several repeats, while others are apparently unique. Gp38, a phage chaperone
      protein necessary for folding of gp37, is thought to act on an alpha-helical
      coiled-coil region in gp37. Future studies should reveal the remaining structure
      of the long tail fibers, how they assemble into a functional unit, and how the
      long tail fibers trigger the infection process after successful recognition of a
      suitable host bacterium.

PMID- 29204884
TI  - Structure and assembly mechanism of virus-associated pyramids.
AB  - Viruses have developed intricate molecular machines to infect, replicate within
      and escape from their host cells. Perhaps one of the most intriguing of these
      mechanisms is the pyramidal egress structure that has evolved in archaeal
      viruses, such as SIRV2 or STIV1. The structure and mechanism of these virus
      associated pyramids (VAPs) has been studied by cryo-electron tomography and
      complementary biochemical techniques, revealing that VAPs are formed by multiple
      copies of a virus-encoded 10-kDa protein (PVAP) that integrate into the cell
      membrane and assemble into hollow, sevenfold symmetric pyramids. In this process,
      growing VAPs puncture the protective surface layer and ultimately open to release
      newly replicated viral particles into the surrounding medium. PVAP has the
      striking capability to spontaneously integrate and self-assemble into VAPs in
      biological membranes of the archaea, bacteria and eukaryotes. This renders the
      VAP a universal membrane remodelling system. In this review, we provide an
      overview of the VAP structure and assembly mechanism and discuss the possible use
      of VAPs in nano-biotechnology.

PMID- 29204886
TI  - Membrane-mediated amyloid deposition of human islet amyloid polypeptide.
AB  - Amyloid deposition of human islet amyloid polypeptide (hIAPP) within the islet of
      Langerhans is closely associated with type II diabetes mellitus. Accumulating
      evidence indicates that the membrane-mediated aggregation and subsequent
      deposition of hIAPP are linked to the dysfunction and death of insulin-producing
      pancreatic beta-cells, but the molecular process of hIAPP deposition is poorly
      understood. In this review, I focus on recent in vitro studies utilizing model
      membranes to observe the membrane-mediated aggregation/deposition of hIAPP.
      Membrane surfaces can serve as templates for both hIAPP adsorption and
      aggregation. Using high-sensitivity surface analyzing/imaging techniques that can
      characterize the processes of hIAPP aggregation and deposition at the membrane
      surface, these studies provide valuable insights into the mechanism of membrane
      damage caused by amyloid deposition of the peptide.

PMID- 29204888
TI  - Initial robotic assistance in the surgical management of renal cell carcinoma
      with level 4 cavoatrial thrombus.
AB  - We report a case of left-sided renal cell carcinoma (RCC) with level 4 cavoatrial
      tumor thrombus where robotic assistance was used to achieve hemostasis around the
      kidney in order to minimize coagulopathic hemorrhage from the nephrectomy bed
      during subsequent open completion nephrectomy and cavoatrial thrombectomy under
      extracorporeal circulation and hypothermic circulatory arrest. Robotic assistance
      allowed for meticulous dissection and ligation of parasitic and arterial vessels
      to the kidney, release of renal attachments, and exposure of the inferior vena
      cava. The kidney was mobilized while leaving the renal vein attached and tumor
      thrombus undisturbed using a "minimal touch" technique. Open completion
      nephrectomy and cavoatrial thrombectomy was then performed. An experienced
      cardiac anesthesia team performed intraoperative cardiac monitoring, including
      trans-esophageal echocardiography. A cardiothoracic surgeon was immediately
      available throughout the case. Cardiopulmonary bypass was initiated within 60 min
      of open incision with a total duration a circulatory arrest time of 25 min. There
      was no bleeding from the nephrectomy bed during bypass despite heparinization and
      hypothermia. A left RCC with level 4 thrombus may be approached with initial
      robotic assistance to achieve hemostasis of the nephrectomy bed for subsequent
      open completion nephrectomy and cavoatrial thrombectomy under extracorporeal
      circulation and hypothermic circulatory arrest.

PMID- 29204887
TI  - Molecular evolution of an oligomeric biocatalyst functioning in lysine
      biosynthesis.
AB  - Dihydrodipicolinate synthase (DHDPS) is critical to the production of lysine
      through the diaminopimelate (DAP) pathway. Elucidation of the function,
      regulation and structure of this key class I aldolase has been the focus of
      considerable study in recent years, given that the dapA gene encoding DHDPS has
      been found to be essential to bacteria and plants. Allosteric inhibition by
      lysine is observed for DHDPS from plants and some bacterial species, the latter
      requiring a histidine or glutamate at position 56 (Escherichia coli numbering)
      over a basic amino acid. Structurally, two DHDPS monomers form the active site,
      which binds pyruvate and (S)-aspartate beta-semialdehyde, with most dimers
      further dimerising to form a tetrameric arrangement around a solvent-filled
      centre cavity. The architecture and behaviour of these dimer-of-dimers is
      explored in detail, including biophysical studies utilising analytical
      ultracentrifugation, small-angle X-ray scattering and macromolecular
      crystallography that show bacterial DHDPS tetramers adopt a head-to-head
      quaternary structure, compared to the back-to-back arrangement observed for plant
      DHDPS enzymes. Finally, the potential role of pyruvate in providing substrate
      mediated stabilisation of DHDPS is considered.

PMID- 29204889
TI  - Authorization of tissues from deceased patients for genetic research.
AB  - Tissues from deceased donors provide important data for genomic research and
      Organ Procurement Organizations (OPOs) play a significant role. To understand the
      decisions of families who donated for transplantation and made decisions about
      donation to the Genotype-Tissue Expression Project (GTEx), we examined donation
      decisions of family decision makers (FDMs). 413 families were interviewed by
      telephone. The OPO staff who made the transplant and research requests completed
      self-administered surveys; a total of 309 matching surveys from 99 OPO staff were
      obtained. 76.8% of families donated to the GTEx project. Logistic regression
      analysis found that FDM consent to GTEx donation was associated with endorsement
      of policies to promote biobanking (OR = 1.35), positive attitudes about medical
      research (OR = 1.1), lack of concern regarding a breach of confidentiality (OR =
      1.54), comfort with tissue donation (OR = 1.24), and prior authorization to solid
      organ donation (OR = 3.17). OPO staff characteristics associated with GTEx
      donation included being female (OR = 3.57), White (OR = 4.97), comfort with
      hospital staff role in donation (OR = 1.61), and number of topics discussed with
      families (OR = 57.9). Donor type, FDM attitudes, OPO staff sociodemographics, OPO
      comfort with the GTEx authorization process, and intensity of discussing research
      specific issues were significantly associated with GTEx donation decisions.

PMID- 29204890
TI  - DNA Cryptography and Deep Learning using Genetic Algorithm with NW algorithm for
      Key Generation.
AB  - Cryptography is not only a science of applying complex mathematics and logic to
      design strong methods to hide data called as encryption, but also to retrieve the
      original data back, called decryption. The purpose of cryptography is to transmit
      a message between a sender and receiver such that an eavesdropper is unable to
      comprehend it. To accomplish this, not only we need a strong algorithm, but a
      strong key and a strong concept for encryption and decryption process. We have
      introduced a concept of DNA Deep Learning Cryptography which is defined as a
      technique of concealing data in terms of DNA sequence and deep learning. In the
      cryptographic technique, each alphabet of a letter is converted into a different
      combination of the four bases, namely; Adenine (A), Cytosine (C), Guanine (G) and
      Thymine (T), which make up the human deoxyribonucleic acid (DNA). Actual
      implementations with the DNA don't exceed laboratory level and are expensive. To
      bring DNA computing on a digital level, easy and effective algorithms are
      proposed in this paper. In proposed work we have introduced firstly, a method and
      its implementation for key generation based on the theory of natural selection
      using Genetic Algorithm with Needleman-Wunsch (NW) algorithm and Secondly, a
      method for implementation of encryption and decryption based on DNA computing
      using biological operations Transcription, Translation, DNA Sequencing and Deep
      Learning.

PMID- 29204891
TI  - Spatial scales of living cells and their energetic and informational capacity.
AB  - Physical (thermodynamic and kinetic), chemical, and biological reasoning restrict
      the spatial dimensions of living cells (prokaryotic and eukaryotic) and confine
      them to between 1 and 100 um. Cells should necessarily be macroscopic,
      dissipative objects, resisting thermal fluctuations and providing sufficient
      informational capacity. The upper limit of the spatial dimensions of cells is
      supplied by their ability to withstand gravity and inertia forces under
      reasonable deformations. The upper limit of cell dimensions is also governed by
      the hierarchy of characteristic time scales, inherent for mass and heat
      transport. For micron-scaled cells, the "traffic time" (namely a typical time
      necessary for the migration of one enzyme to another) is on the order of
      magnitude of a millisecond, which coincides with the characteristic time scale of
      a single round of the catalytic enzyme cycle. The macroscopic dimensions of
      living cells (seen as dissipative systems) and the hierarchy of time scales of
      the mass transfer processes vs. those inherent for heat transport and viscous
      dissipation give rise to the irreversibility of biological processes.

PMID- 29204892
TI  - Erratum to: HPLC Determination of Bioactive Sulfur Compounds, Amino Acids and
      Biogenic Amines in Biological Specimens.

PMID- 29204893
TI  - The Development of a Patient-Reported Outcome Measure for Assessment of Genital
      Psoriasis Symptoms: The Genital Psoriasis Symptoms Scale (GPSS).
AB  - INTRODUCTION: Patient-reported outcome measures (PROs) specific for genital
      psoriasis (GenPs) have not been described. METHODS: In this cross-sectional,
      qualitative study in patients with moderate-to-severe GenPs, we sought to develop
      a PRO useful for GenPs symptom assessment. A literature review was performed to
      identify relevant psoriasis or GenPs symptoms and existing PROs that may be
      useful in the evaluation of symptom severity in GenPs patients. The literature
      review findings were discussed with clinicians, and then patients with GenPs.
      RESULTS: Relevant psoriasis or GenPs symptoms from the literature review included
      itch, pain, scaling, redness/erythema, and stinging/burning. The validity of
      these symptoms for GenPs and potentially relevant PROs was corroborated by
      clinical experts. After gap analysis, a draft symptom scale consisting of Numeric
      Rating Scale (NRS) items was constructed. We then conducted interviews with GenPs
      patients (n = 20) to support content validity and use of the draft symptom NRS
      items in routine practice and in clinical trials. Participants identified and
      confirmed relevant symptoms and evaluated the utility of the draft PRO. A new PRO
      was developed: the Genital Psoriasis Symptoms Scale (GPSS). Cognitive debriefing
      and cultural adaptation/translation interviews with a second group of patients
      confirmed cultural appropriateness of the GPSS. CONCLUSION: The GPSS may be
      useful for assessing symptoms before, during, and after treatment in routine
      clinical practice and in clinical trials involving patients with GenPs. FUNDING:
      Eli Lilly & Company. Plain language summary available for this article.

PMID- 29204894
TI  - The Development of the Genital Psoriasis Sexual Frequency Questionnaire (GenPs
      SFQ) to Assess the Impact of Genital Psoriasis on Sexual Health.
AB  - INTRODUCTION: Patient-reported outcome measures (PROs) exist for psoriasis but
      not genital psoriasis (GenPs). METHODS: This cross-sectional, qualitative study
      in patients with moderate-to-severe GenPs was conducted to support development of
      a PRO for measuring the impact of GenPs on sexual activity and to establish
      content validity. The impacts of GenPs were identified in a literature review.
      Findings from the literature review were discussed with clinicians, and then
      patients with GenPs were interviewed. RESULTS: From the literature review, 52
      articles, 44 abstracts, and 41 clinical trials met predefined search criteria. Of
      these, 11 concepts emerged as having theoretical support for use as measurable
      impacts of psoriasis symptoms on patients; these concepts included sexual
      functioning and general health-related quality of life (HRQoL). These concepts
      were confirmed and expanded upon by two clinicians who routinely care for
      patients with GenPs. Interviews were then conducted with GenPs patients (n = 20)
      to discuss the impact of GenPs on their HRQoL. Eighty percent of patients
      reported that GenPs impacted sexual frequency. The two-item GenPs Sexual
      Frequency Questionnaire (GenPs-SFQ) was developed to assess limitations on sexual
      activity frequency because of GenPs. Cognitive debriefing with an additional 50
      patients with GenPs confirmed the utility and understandability of the GenPs-SFQ.
      CONCLUSION: The GenPs-SFQ may have utility in clinical trials involving GenPs
      patients and in routine clinical practice. FUNDING: Eli Lilly and Company. Plain
      language summary available for this article.

PMID- 29204895
TI  - The development of a healing model of care for an Indigenous drug and alcohol
      residential rehabilitation service: a community-based participatory research
      approach.
AB  - BACKGROUND: Given the well-established evidence of disproportionately high rates
      of substance-related morbidity and mortality after release from incarceration for
      Indigenous Australians, access to comprehensive, effective and culturally safe
      residential rehabilitation treatment will likely assist in reducing recidivism to
      both prison and substance dependence for this population. In the absence of
      methodologically rigorous evidence, the delivery of Indigenous drug and alcohol
      residential rehabilitation services vary widely, and divergent views exist
      regarding the appropriateness and efficacy of different potential treatment
      components. One way to increase the methodological quality of evaluations of
      Indigenous residential rehabilitation services is to develop partnerships with
      researchers to better align models of care with the client's, and the
      community's, needs. An emerging research paradigm to guide the development of
      high quality evidence through a number of sequential steps that equitably
      involves services, stakeholders and researchers is community-based participatory
      research (CBPR). The purpose of this study is to articulate an Indigenous drug
      and alcohol residential rehabilitation service model of care, developed in
      collaboration between clients, service providers and researchers using a CBPR
      approach. METHODS/DESIGN: This research adopted a mixed methods CBPR approach to
      triangulate collected data to inform the development of a model of care for a
      remote Indigenous drug and alcohol residential rehabilitation service. RESULTS:
      Four iterative CBPR steps of research activity were recorded during the 3-year
      research partnership. As a direct outcome of the CBPR framework, the service and
      researchers co-designed a Healing Model of Care that comprises six core treatment
      components, three core organisational components and is articulated in two
      program logics. The program logics were designed to specifically align each
      component and outcome with the mechanism of change for the client or organisation
      to improve data collection and program evaluation. CONCLUSION: The description of
      the CBPR process and the Healing Model of Care provides one possible solution
      about how to provide better care for the large and growing population of
      Indigenous people with substance.

PMID- 29204897
TI  - Construction of a cellulose-metabolizing Komagataella phaffii (Pichia pastoris)
      by co-expressing glucanases and beta-glucosidase.
AB  - Cellulose is a highly available and renewable carbon source in nature. However,
      it cannot be directly metabolized by most microbes including Komagataella phaffii
      (formerly Pichia pastoris), which is a frequently employed host for heterologous
      protein expression and production of high-value compounds. A K. phaffii strain
      was engineered that constitutively co-expresses an endoglucanase and a beta
      glucosidase both from Aspergillus niger and an exoglucanase from Trichoderma
      reesei under the control of bidirectional promoters. This engineered strain was
      able to grow on cellobiose and carboxymethyl cellulose (CMC) but not on Avicel.
      However, the detected release of cellobiose from Avicel by using the produced
      mixture of endoglucanase and exoglucanase as well as the released glucose from
      Avicel by using the produced mixture of all three cellulases at 50  degrees C
      indicated the production of exoglucanase under the liquid culture conditions. The
      successful expression of three cellulases in K. phaffii demonstrated the
      feasibility to enable K. phaffii to directly use cellulose as a carbon source for
      producing recombinant proteins or other high-value compounds.

PMID- 29204896
TI  - A comparison of tumour size measurements with palpation, ultrasound and
      mammography in male breast cancer: first results of the prospective register
      study.
AB  - PURPOSE: Precise presurgical diagnosis of tumour size is essential for adequate
      treatment of male breast cancer (MBC). This study is aimed to compare the
      accuracy of clinical measurement (CE), ultrasound (US) and mammography (MG) for
      preoperative estimation of tumour size. METHODS: This study was conducted as a
      prospective, multicentre register study. One hundred and twenty-nine male
      patients with invasive breast cancer were included. CE, US and MG were performed
      in 107, 110 and 75 patients, respectively, and the estimated tumour size was
      compared with the histopathological (HP) tumour size. RESULTS: All methods tended
      to underestimate the HP tumour size. None of the methods were significantly more
      accurate than the others in determining the maximal tumour diameter. The
      sensitivity within 5 mm tolerance for US was 65.5%, which was better than for MG
      (61.3%) and CE (56.6%). In the group of patients with pT2 tumours, MG showed
      significantly better accuracy than US. The measurements obtained with each method
      were significantly correlated with the HP measurements. The highest correlation
      coefficient was observed for MG (0.788), followed by US (0.741) and CE (0.671).
      CONCLUSIONS: Our data demonstrate that MG and US have similar accuracy with
      regard to tumour size estimation. US assessment showed the highest sensitivity in
      determining tumour size, followed by MG and CE. However, MG demonstrated a
      significant advantage for estimating the real tumour size for pT2 tumours
      compared to US or CE.

PMID- 29204898
TI  - High-rate nitrogen removal from waste brine by marine anammox bacteria in a pilot
      scale UASB reactor.
AB  - The goal of this study was to develop a startup strategy for a high-rate
      anaerobic ammonium oxidation (anammox) reactor to treat waste brine with high
      concentrations of ammonium from a natural gas plant. An upflow anaerobic sludge
      blanket (UASB) anammox reactor with an effective volume of 294 L was fed
      continuously with waste brine with a salinity of 3% and a NH4+ concentration of
      180 mg-N/L, as well as a NaNO2 solution. By inoculating a methanogenic granular
      biomass as a biomass carrier, the reactor attained the maximum volumetric
      nitrogen removal rate (NRR) of 10.7 kg-N/m3/day on day 209, which was 1.7 times
      higher than the highest reported NRR for wastewater of comparable salinity. High
      throughput sequencing of 16S rRNA gene amplicons revealed that Candidatus
      Scalindua wagneri was enriched successfully in granules in the UASB, and it
      replaced Methanosaeta and became dominant in the granule. The inhibitory effect
      of NO2- on the anammox reaction in the granules was assessed by a 15N tracer
      method, and the results showed that anammox activity was maintained at 60% after
      exposure to 300 mg-N/L of NO2- for 24 h. Compared with previous studies of the
      susceptibilities of Candidatus Brocadia and Candidatus Kuenenia to NO2-, the
      enriched marine anammox bacteria were proven to have comparable or even higher
      tolerances for high NO2- concentrations after a long exposure.

PMID- 29204899
TI  - Secondary metabolism in Fusarium fujikuroi: strategies to unravel the function of
      biosynthetic pathways.
AB  - The fungus Fusarium fujikuroi causes bakanae disease of rice due to its ability
      to produce the plant hormones, the gibberellins. The fungus is also known for
      producing harmful mycotoxins (e.g., fusaric acid and fusarins) and pigments
      (e.g., bikaverin and fusarubins). However, for a long time, most of these well
      known products could not be linked to biosynthetic gene clusters. Recent genome
      sequencing has revealed altogether 47 putative gene clusters. Most of them were
      orphan clusters for which the encoded natural product(s) were unknown. In this
      review, we describe the current status of our research on identification and
      functional characterizations of novel secondary metabolite gene clusters. We
      present several examples where linking known metabolites to the respective
      biosynthetic genes has been achieved and describe recent strategies and methods
      to access new natural products, e.g., by genetic manipulation of pathway-specific
      or global transcritption factors. In addition, we demonstrate that deletion and
      over-expression of histone-modifying genes is a powerful tool to activate silent
      gene clusters and to discover their products.

PMID- 29204900
TI  - Molecular design for recombinant adeno-associated virus (rAAV) vector production.
AB  - Recombinant adeno-associated virus (rAAV) vectors are increasingly popular tools
      for gene therapy applications. Their non-pathogenic status, low inflammatory
      potential, availability of viral serotypes with different tissue tropisms, and
      prospective long-lasting gene expression are important attributes that make rAAVs
      safe and efficient therapeutic options. Over the last three decades, several
      groups have engineered recombinant AAV-producing platforms, yielding high titers
      of transducing vector particles. Current specific productivity yields from
      different platforms range from 103 to 105 vector genomes (vg) per cell, and there
      is an ongoing effort to improve vector yields in order to satisfy high product
      demands required for clinical trials and future commercialization.Crucial aspects
      of vector production include the molecular design of the rAAV-producing host cell
      line along with the design of AAV genes, promoters, and regulatory elements.
      Appropriately, configuring and balancing the expression of these elements not
      only contributes toward high productivity, it also improves process robustness
      and product quality. In this mini-review, the rational design of rAAV-producing
      expression systems is discussed, with special attention to molecular strategies
      that contribute to high-yielding, biomanufacturing-amenable rAAV production
      processes. Details on molecular optimization from four rAAV expression systems
      are covered: adenovirus, herpesvirus, and baculovirus complementation systems, as
      well as a recently explored yeast expression system.

PMID- 29204901
TI  - Cell culture-based production of defective interfering particles for influenza
      antiviral therapy.
AB  - Defective interfering particles (DIPs) lack an essential portion of the virus
      genome, but retain signals for replication and packaging, and therefore,
      interfere with standard virus (STV) replication. Due to this property, DIPs can
      be potential antivirals. The influenza A virus DIP DI244, generated during
      propagation in chicken eggs, has been previously described as a potential
      candidate for influenza antiviral therapy. As a cell culture-based manufacturing
      process would be more suitable to fulfill large-scale production needs of an
      antiviral and enables full process control in closed systems, we investigated
      options to produce DI244 in the avian cell line AGE1.CR.pIX in chemically defined
      suspension culture. With a DI244 fraction of 55.8% compared to STV, the highest
      DI244 yield obtained from 50 million cells was 4.6 * 109 vRNA copies/mL at 12 h
      post infection. However, other defective genomes were also detected. Since these
      additionally produced defective particles are non-infectious, they might be still
      useful in antiviral therapies. In case they would interfere with quality of the
      final product, we examined the impact of virus seeds and selected process
      parameters on DI244 yield and contamination level with other defective particles.
      With a DI244 fraction of 5.5%, the yield obtained was 1.7 * 108 vRNA copies/mL
      but now without additional defective genomes. Although the DI244 yield might be
      decreased in this case, such controlled manufacturing conditions are not
      available in chicken eggs. Overall, the application of these findings can support
      design and optimization of a cell culture-based production process for DIPs to be
      used as antivirals.

PMID- 29204902
TI  - Diet and risk of diabetic retinopathy: a systematic review.
AB  - Diabetic retinopathy is a microvascular complication of diabetes that threatens
      all individuals with diabetes, leading to vision loss or blindness if left
      untreated. It is frequently associated with diabetic macular edema, which can
      occur at any point during the development of diabetic retinopathy. The key
      factors known to lead to its development include hyperglycemia, hypertension, and
      the duration of diabetes. Though the diet is important in the development of
      diabetes, its role in diabetic retinopathy has not been clearly identified. In
      this systematic review, we aimed to identify, summarize and interpret the
      literature on the association between the diet and dietary intakes of specific
      foods, nutrients, and food groups, and the risk of diabetic retinopathy. We
      searched PubMed and Web of Science for English-language studies evaluating the
      association between the dietary intake of individual foods, macro or
      micronutrients, dietary supplements, and dietary patterns and their association
      with retinopathy or macular edema. After reviewing potentially relevant abstracts
      and, when necessary, full texts, we identified 27 relevant studies. Identified
      studies investigated intakes of fruit, vegetables, fish, milk, carbohydrates,
      fibre, fat, protein, salt, potassium, vitamins C, D, and E, carotenoids, dietary
      supplements, green tea and alcohol. Studies suggest that adherence to the
      Mediterranean diet and high fruit, vegetable and fish intake may protect against
      the development of diabetic retinopathy, although the evidence is limited.
      Studies concerning other aspects of the diet are not in agreement. The role of
      the diet in the development of diabetic retinopathy is an area that warrants more
      attention.

PMID- 29204903
TI  - Selection of reference groups in the Life Span Study of atomic bomb survivors.
AB  - In cohort studies, unbiased estimation of exposure-outcome associations requires
      selection of an appropriate reference group of unexposed individuals. We
      illustrate strategies for analyzing cohort data with multiple potential reference
      groups. We analyzed the association between radiation exposure and incidence of
      first primary solid cancer among 105,444 participants of the Life Span Study
      (Hiroshima and Nagasaki, Japan, 1958-2009). Potential reference groups included
      zero-dose survivors at different ground distances from the hypocenter (internal)
      and city residents who were not in either city at the time of the bombings
      (external). DS02R1 weighted absorbed colon doses were estimated by the DS02
      dosimetry system. Piecewise constant hazard models estimated excess relative
      risks of first primary solid cancer. We focused on sex-averaged excess relative
      risks and the shape of the dose-response curve. A model with internal
      standardization provided a sex-averaged excess relative risk of 0.510, 95%
      confidence interval: (0.414, 0.612) per gray of weighted absorbed colon dose, as
      well as strong evidence of a curvilinear dose response among males (P = 0.008).
      Selection of not-in-city residents as the reference group resulted in a larger
      excess relative risk of 0.560, 95% confidence interval: (0.467, 0.657) per gray,
      and reduced evidence of a curvilinear dose response among males (P = 0.042).
      These differences were particularly apparent at weighted absorbed colon doses < 1
      gray. In cohort studies, selection of an appropriate reference group requires
      understanding of the nature of unmeasured confounding to which the results could
      be sensitive.

PMID- 29204904
TI  - The functionality of African-specific variants in the TGFB1 regulatory region and
      their potential role in HIVAN.
AB  - BACKGROUND: Transcription of transforming growth factor beta-1 (TGF-beta1) is
      regulated by a polymorphic promoter region containing African-specific single
      nucleotide polymorphisms (SNPs). Some of these SNPs have higher frequencies among
      Southern Africans compared to other African populations and their functionality
      has only been partially studied. Due to the high prevalence of HIV-associated
      nephropathy (HIVAN) in Africans we hypothesized that functional African TGFB1
      promoter SNPs may contribute to HIVAN pathogenesis. METHODS: The functionality of
      the TGFB1 -1347 C>T variant and African-specific variants (-1287 G>A, -1154 C>T, 
      387 C>T and -14 G>A) were examined by measuring reporter gene expression in
      kidney and fibroblast cell lines co-transfected with TGFB1-promoter constructs
      and an HIV-Tat expression vector. TGF-beta1 immunohistochemical staining was
      performed on kidney biopsies with HIVAN (n = 18) and compared to control biopsies
      without HIVAN or tubulointerstitial disease (n = 12) using semi-quantitative and
      digital image analysis. HIVAN cases were genotyped for TGFB1 -1347 and -387 SNP
      variants. RESULTS: TGFB1-promoter haplotypes containing the African -387 T-allele
      resulted in ~ five-fold repression of TGFB1-promoter activity compared to -387 C
      haplotypes (p <= 0.024). HIV-Tat upregulated TGFB1-promoter activity for
      haplotypes containing -1347 T and -387 T in transfected renal cells (~ 1.6-fold;
      p <= 0.030) and fibroblasts (~ 1.3-fold; p <= 0.016). The renal interstitium from
      HIVAN biopsies, compared to HIV-positive and -negative controls, differed in the
      semi-quantitative TGF-beta1 staining and digital optical density analyses. The
      TGFB1 -1347 and -387 genotypes in HIVAN cases were similar to population
      controls. CONCLUSION: African-specific haplotypes lower TGFB1-promoter activity
      and expression levels and HIV-Tat upregulates TGFB1 promoter activity
      irrespective of the haplotype.

PMID- 29204906
TI  - Mapping QTL for Omega-3 Content in Hybrid Saline Tilapia.
AB  - Tilapia is one of most important foodfish species. The low omega-3 to omega-6
      fatty acid ratio in freshwater tilapia meat is disadvantageous for human health.
      Increasing omega-3 content is an important task in breeding to increase the
      nutritional value of tilapia. However, conventional breeding to increase omega-3
      content is difficult and slow. To accelerate the increase of omega-3 through
      marker-assisted selection (MAS), we conducted QTL mapping for fatty acid contents
      and profiles in a F2 family of saline tilapia generated by crossing red tilapia
      and Mozambique tilapia. The total omega-3 content in F2 hybrid tilapia was 2.5 +/
      1.0 mg/g, higher than that (2.00 mg/g) in freshwater tilapia. Genotyping by
      sequencing (GBS) technology was used to discover and genotype SNP markers, and
      microsatellites were also genotyped. We constructed a linkage map with 784
      markers (151 microsatellites and 633 SNPs). The linkage map was 2076.7 cM long
      and consisted of 22 linkage groups. Significant and suggestive QTL for total
      lipid content were mapped on six linkage groups (LG3, -4, -6, -8, -13, and -15)
      and explained 5.8-8.3% of the phenotypic variance. QTL for omega-3 fatty acids
      were located on four LGs (LG11, -18, -19, and -20) and explained 5.0 to 7.5% of
      the phenotypic variance. Our data suggest that the total lipid and omega-3 fatty
      acid content were determined by multiple genes in tilapia. The markers flanking
      the QTL for omega-3 fatty acids can be used in MAS to accelerate the genetic
      improvements of these traits in salt-tolerant tilapia.

PMID- 29204905
TI  - Intracorporeal lithotripsy.
AB  - Since the introduction of ESWL, PNL and URS during the early 1980s the
      application rate of ESWL has declined while those of PNL and URS have increased.
      This is mainly due to the facts that instruments and techniques for
      Intracorporeal Lithotripsy (IL) have made a continuous progress. This review
      shows that today an array of options for IL within the entire urinary tract is
      available to treat stones in a perfect minimal invasive way. At the same time
      further improvements of IL are already visible.

PMID- 29204907
TI  - Does the Addition of Biologic Agents to Chemotherapy in Patients with
      Unresectable Colorectal Cancer Metastases Result in a Higher Proportion of
      Patients Undergoing Resection? A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Surgical resection provides the best opportunity for cure for
      metastatic colorectal cancer. Whether addition of a biologic agent to
      chemotherapy improves the rate of conversion from unresectable to resectable
      disease remains uncertain. We carried out a systematic review of the literature
      and meta-analysis to define the impact of biologic agents on resection. METHODS:
      We searched Medline, Embase, CENTRAL, and PubMed for randomized controlled trials
      published up until April 2017 comparing chemotherapy and biologics (intervention)
      vs. chemotherapy alone (control) in treatment-naive patients with unresectable
      metastatic colorectal cancer. Study selection, data abstraction, risk of bias,
      and quality of evidence assessment were performed in duplicate. Random-effects
      meta-analysis was used to estimate the pooled odds ratio (OR) for resection rate
      and corresponding confidence interval (CI). RESULTS: Nine studies, including a
      total of 4345 patients, were analyzed. Seven studies assessed epithelial growth
      factor receptor (EGFR)-directed monoclonal antibodies, and two used
      antiangiogenic agents. The addition of a biologic agent to chemotherapy was
      associated with higher resection rate (OR 1.47, 95% CI 1.07-2.02; resection rate
      8.4 vs. 6.1%). Subgroup analysis based on mechanism of action of drugs showed
      benefit for resection rate only with EGFR-directed agents (OR 1.70, 95% CI 1.10
      2.64). Heterogeneity among studies was low (I 2  = 34%). CONCLUSIONS: The
      addition of biologic agents to systemic chemotherapy in patients with initially
      unresectable metastatic colorectal cancer improved resection rate. The optimal
      biologic agent for this outcome cannot yet be determined.

PMID- 29204908
TI  - Posttraumatic stress disorder due to acute cardiac events and aversive cognitions
      towards cardiovascular medications.
AB  - Posttraumatic stress disorder (PTSD) after acute medical events is associated
      with medication nonadherence. The mechanisms of PTSD-related nonadherence are
      poorly understood. We tested whether patients with elevated PTSD symptoms induced
      by suspected acute coronary syndrome (ACS) were more likely to have aversive
      cognitions towards cardiovascular medications. We enrolled a consecutive cohort
      of patients who presented to the emergency department with suspected ACS. One
      month after discharge, ACS-induced PTSD symptoms were assessed using the PTSD
      Checklist (PCL-S), and patients were asked "how often did" (1) "you miss your
      heart medication because you did not want to be reminded about your heart
      problem"; (2) "thinking about your heart medication make you feel nervous or
      anxious"; and (3) "thinking about your heart medication make you think about your
      risk for future heart problems." Logistic regression was used to determine the
      association between elevated PTSD symptoms and each aversive cognition, adjusting
      for age, sex, race, ethnicity, education, depression, and ACS status. Of 424
      patients included, 15.8% had elevated PTSD symptoms (PCL-S >= 34). In adjusted
      analyses, higher PCL-S scores were associated with missing medications to avoid
      reminders of heart disease (OR 1.22 per 5-point PCL-S increase, 95%CI 1.07-1.40),
      as well as anxiety (OR 1.34, 95%CI 1.19-1.51) and thoughts of future risk (OR
      1.19, 95%CI 1.08-1.32) when thinking about cardiovascular medications. We
      concluded that patients with elevated PTSD symptoms following suspected ACS were
      more likely to report aversive cognitions about their cardiovascular medications,
      suggesting that medications can act as traumatic reminders of the cardiac event
      and ongoing risk in this group.

PMID- 29204909
TI  - Nano-Se Assimilation and Action in Poultry and Other Monogastric Animals: Is Gut
      Microbiota an Answer?
AB  - Recently, a comprehensive review paper devoted to roles of nano-Se in livestock
      and fish nutrition has been published in the Nanoscale Research Letters. The
      authors described in great details an issue related to nano-Se production and its
      possible applications in animal industry and medicine. However, molecular
      mechanisms of nano-Se action were not described and the question of how nano-Se
      is converted into active selenoproteins is not resolved. It seems likely that the
      gut microbiota can convert nano-Se into selenite, H2Se or Se-phosphate with the
      following synthesis of selenoproteins. This possibility needs to be further
      studied in detail, and advantages and disadvantages of nano-Se as a source of Se
      in animal/poultry/fish nutrition await critical evaluations.

PMID- 29204910
TI  - Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific
      Evidence with a Focus on Hematopoietic Cell Transplantation.
AB  - Cytomegalovirus (CMV) is an agent of global infection, and its acquisition in a
      population is characterized by an age-dependent rise in seropositivity. After
      primary infection, CMV remains in the host cells in latent form, and it can
      reactivate in the case of immune suppression. The risk of CMV recurrence is
      dependent on the level of incompetency of the immune system, manifested as an
      impairment of T-cell immunity, including the presence and function of CMV
      specific cytotoxic T lymphocytes. This article presents data on the incidence of
      CMV recurrence in groups of immunocompromised patients, including allogeneic
      hematopoietic stem cell transplantation (HSCT) patients and other groups of
      patients, based on a summary of reported data. The median rate of CMV recurrence
      in HSCT recipients was estimated as 37% after allogeneic transplant and 12% after
      autologous transplant, 5% in patients with nontransplant hematological
      malignancies, 14% in recipients of anti-CD52 therapy, 30% in solid organ
      transplant recipients, 21% in patients with primary immunodeficiencies, 20%
      during active replication in HIV-positive patients and 3.3% during antiretroviral
      therapy, 7% in patients with chronic kidney disease, 0.6% in patients with
      congenital infection, and 0.6% in neonates with primary infection. The highest
      risk of CMV recurrence and CMV disease is reported for HSCT CMV-seropositive
      recipients, regardless of donor serostatus. The odds ratio (OR) for CMV
      recurrence is higher for recipient-positive versus recipient-negative CMV
      serostatus transplants (OR 8.0), donor-negative/recipient-positive versus donor
      positive/recipient-positive CMV serostatus transplants (OR 1.2),
      unrelated/mismatched versus matched-family donor transplants (OR 1.6), and acute
      graft-versus-host-disease versus other diseases (OR 3.2). Other risk factors have
      minor significance.

PMID- 29204911
TI  - Repeated shock stress facilitates basolateral amygdala synaptic plasticity
      through decreased cAMP-specific phosphodiesterase type IV (PDE4) expression.
AB  - Previous studies have shown that exposure to stressful events can enhance fear
      memory and anxiety-like behavior as well as increase synaptic plasticity in the
      rat basolateral amygdala (BLA). We have evidence that repeated unpredictable
      shock stress (USS) elicits a long-lasting increase in anxiety-like behavior in
      rats, but the cellular mechanisms mediating this response remain unclear.
      Evidence from recent morphological studies suggests that alterations in the
      dendritic arbor or spine density of BLA principal neurons may underlie stress
      induced anxiety behavior. Recently, we have shown that the induction of long-term
      potentiation (LTP) in BLA principal neurons is dependent on activation of
      postsynaptic D1 dopamine receptors and the subsequent activation of the cyclic
      adenosine 5'-monophosphate (cAMP)-protein kinase A (PKA) signaling cascade. Here,
      we have used in vitro whole-cell patch-clamp recording from BLA principal neurons
      to investigate the long-term consequences of USS on their morphological
      properties and synaptic plasticity. We provided evidence that the enhanced
      anxiety-like behavior in response to USS was not associated with any significant
      change in the morphological properties of BLA principal neurons, but was
      associated with a changed frequency dependence of synaptic plasticity, lowered
      LTP induction threshold, and reduced expression of phosphodiesterase type 4
      enzymes (PDE4s). Furthermore, pharmacological inhibition of PDE4 activity with
      rolipram mimics the effects of chronic stress on LTP induction threshold and
      baseline startle. Our results provide the first evidence that stress both
      enhances anxiety-like behavior and facilitates synaptic plasticity in the
      amygdala through a common mechanism of PDE4-mediated disinhibition of cAMP-PKA
      signaling.

PMID- 29204913
TI  - Trends in prostate cancer incidence between 1996 and 2013 in two Swiss regions by
      age, grade, and T-stage.
AB  - PURPOSE: To investigate differences in prostate cancer incidence between two
      distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T
      stage. METHODS: The dataset included 17,495 men living in Zurich and 3,505 men
      living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We
      computed age-standardized incidence rates per 100,000 person-years using the
      European Standard Population. Trends were assessed using JoinPoint regression
      analysis Software. RESULTS: Age-standardized incidence rates were generally
      higher in Zurich compared to Ticino but the difference decreased over time.
      Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino
      and then decreased. A statistically significant increase was observed for men
      aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest
      decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of
      unknown grade or T-stage decreased significantly in both regions. CONCLUSIONS:
      The trends in prostate cancer incidence rates were similar in both regions,
      although on a higher level in Zurich compared to Ticino. However, the difference
      decreased over time. The distribution of T-stage and grade did not explain the
      difference in incidence rates. Different use of opportunistic screening may play
      a role.

PMID- 29204912
TI  - Should subcentimeter non-invasive encapsulated, follicular variant of papillary
      thyroid carcinoma be included in the noninvasive follicular thyroid neoplasm with
      papillary-like nuclear features category?
AB  - OBJECTIVE: In 2016, non-invasive, well-circumscribed and encapsulated, follicular
      variant of papillary thyroid carcinoma (NI-EFV PTC) was reclassified as
      noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      (NIFTP) in order to reduce overtreatment of this indolent tumor. However, the
      study cohort did not include subcentimeter tumors, i.e., papillary thyroid
      microcarcinoma (mPTC) with NI-EFV morphology, and such lesions are still regarded
      and staged by most pathologists as microcarcinomas. It is therefore crucial to
      evaluate the clinical outcome of subcentimeter NI-EFVs. METHODS: A total of 52
      patients with unifocal mPTC, NI-EFV from five tertiary hospitals who had at least
      one year clinical follow-up (FU) without post-operative RAI administration were
      included in the study. A control group of 57 invasive mPTC follicular variant was
      also included. RESULTS: The median tumor size was 0.44 cm (range 0.1-0.9 cm).
      There were no distant or lymph node metastases at diagnosis in all patients.
      Twenty-three patients (44%) underwent lobectomy alone, while the remaining
      received total thyroidectomy. No recurrence was observed in the entire cohort (n
      = 52) including all 38 patients with at least 2 years of FU (median FU: 6.3
      years). Among 25 patients with >=5 years of FU, none recurred with a median FU of
      9.6 years (range 5.2-18.1 years). In contrast, in the control group with invasive
      mPTC follicular variant, there were 5 (9%) patients with nodal metastasis at
      presentation and 1 (2%) who displayed nodal recurrence. CONCLUSION: Papillary
      thyroid microcarcinoma, NI-EFV, when stringently selected for, lacks metastasis
      at presentation and follows an extremely indolent clinical course, even when
      treated conservatively without RAI therapy. Provided stringent inclusion criteria
      are met, classification of subcentimeter mPTC, NI-EFV as NIFTP should be
      considered in order to avoid overtreatment of these biologically indolent
      lesions.

PMID- 29204914
TI  - Muscle fiber conduction velocity and EMG amplitude of the upper trapezius muscle
      in healthy subjects after low-level laser irradiation: a randomized, double
      blind, placebo-controlled, crossover study.
AB  - Although low-level laser therapy (LLLT) is an important resource for the
      treatment of non-specific neck pain patients, the dose which presents the
      greatest therapeutic potential for the treatment of this pathology is still
      unclear. The present study aimed to evaluate the immediate effect of LLLT on the
      muscle fiber conduction velocity (MFCV) and electromyographic activity (EMG) of
      the upper trapezius (UT) muscle in healthy individuals. A total of 20 healthy
      subjects were enrolled in a randomized, double-blind, crossover study. Active
      LLLT (820 nm wavelength, 30 mW, energy total 18 J) or placebo LLLT (pLLLT) was
      delivered on the UT muscle. Each subject was subjected to a single session of
      active LLLT and pLLLT. Surface electromyography (sEMG) signal of the UT muscle
      was recorded during five different step contractions of shoulder elevation force
      (10-30% maximal voluntary contraction) pre- and post-LLLT irradiation. The values
      of MFCV and sEMG global amplitude (RMSG) were used to calculate the effects of
      LLLT. The results showed no difference in the MFCV comparing the LLLT and pLLLT
      groups (F = 0.72 p = 0.39, eta p2 = 0.004). However, a significant difference was
      observed in the RMSG between the LLLT and pLLLT (F 1,2 = 16.66; P < 0.0001, eta
      p2 = 0.09). Individuals who received active LLLT presented a significant decrease
      in RMSG after laser application (F = 61.28; p < 0.0001, eta p2 = 0.43). In
      conclusion, the 820 nm LLLT, with energy total of 18 J, did not alter the MFCV
      but significantly reduced the sEMG signal amplitude of the upper trapezius muscle
      in healthy subjects to a level of up to 30% of maximal voluntary contraction.

PMID- 29204915
TI  - Is photobiomodulation (PBM) effective for the treatment of dentin
      hypersensitivity? A systematic review.
AB  - The present study aims to evaluate the current scientific data regarding the
      effectiveness of photobiomodulation (PBM) in the treatment of dentin
      hypersensitivity (DH) as an alternative method for pain control. A systematic
      review was conducted to assess the effectiveness of PBM as treatment for DH. A
      complete literature search was performed up to October 2016. Searches were
      conducted using Boolean operators and MeSH terms. References of all selected full
      text articles and related reviews were scanned. A total of 280 articles were
      identified (241 articles were excluded by the title and abstract). Of the 39
      articles selected for analysis, 36 were excluded because they presented one or
      more exclusion criteria. Therefore, three articles were qualified for inclusion
      in this systematic review. PBM may not lead to adverse effects provided that
      adequately controlled parameters are followed when treating DH. More consistent
      studies should be conducted in order to adequately observe the advantageous
      therapeutic effect of PBM.

PMID- 29204916
TI  - RNASEH1 gene variants are associated with autoimmune type 1 diabetes in Colombia.
AB  - BACKGROUND: In a previous work, we found linkage and association of type 1
      diabetes (T1D) to a 12 known gene region at chromosome 2p25 in Colombian
      families. Here, we present further work on this candidate region. MATERIALS AND
      METHODS: Seventeen SNPs located on the 12 candidate genes, in 100 familial trios
      set, were tested by ARMS-tetraprimer-PCR or PCR-RFLP. Five extra SNPs in the
      vicinity of rs10186193 were typed. A replica phase included 97 novel familial
      trios, in whom diabetes-related auto-antibodies (AABs) were tested in sera of the
      patients. In addition to transmission disequilibrium tests, haplotype analyses
      were carried out using the unphased software. RESULTS: SNP rs10186193 (at RNASEH1
      gene) showed association with T1D (P = 0.005). The additional five SNPs revealed
      that rs7607888 (P = 2.03 * 10-7), rs55981318 (P = 0.018), and rs1136545 (P = 1.93
      * 10-9) were also associated with T1D. Haplotype analysis showed association for
      rs55981318-rs10186193 (P = 0.0005), rs7563960-rs7607888 (P = 0.0007), rs7607888
      rs1136545 (P = 9.21 * 10-10), and rs1136545-rs11538545 (P = 6.67 * 10-8). In
      contrast, the new set of 97 familial trios tested for SNPs rs55981318,
      rs10186193, and rs7607888 did not support the previous finding; however, by
      combining the sample (197 trios), evidence of association of T1D with rs55981318
      and rs7607888 was conclusive. In addition, a two-loci haplotype analysis of the
      combined sample showed significant association of RNASEH1 with T1D (P = 3.1 * 10
      5). CONCLUSION: In conclusion, our analyses suggest that RNASEH1 gene variants
      associate with susceptibility/protection to T1D in Colombia.

PMID- 29204917
TI  - The outcome of cochlear implantation among children with genetic syndromes.
AB  - OBJECTIVE: To assess the outcome and efficacy of cochlear implantation in
      children with genetic syndromes. METHOD: Study design: case-control study.
      SETTING: A cochlear implantation tertiary referral center. PATIENTS: All
      pediatric cochlear implantation recipients with Waardenburg syndrome, Usher
      syndrome, Dandy-Walker syndrome, or albinism. A control group was appropriately
      matched to the syndromic group with regard to age at implantation and duration of
      device use. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Subjects'
      auditory abilities, speech intelligibility, and pure tone thresholds were
      compared between the syndromic and non-syndromic group. RESULTS: A total of 25
      subjects (13 syndromic and 12 non-syndromic) participated in the study. Neither
      auditory ability nor speech intelligibility scores differed significantly by
      group. The final PTA of both the groups showed normal-to-mild hearing loss: 26 dB
      HL in the syndromic group and 23 dB HL for the control group. CONCLUSIONS:
      Cochlear implant recipients with genetic syndromes achieved similar levels
      auditory perception and speech intelligibility as their peers with a genetic
      syndrome. The presence of any of the genetic syndromes described herein should
      not be a contraindication to cochlear implant provision, as it would have a
      positive impact on the patients' sensory perception and lifestyle.

PMID- 29204918
TI  - Sialendoscopy in treating pediatric salivary gland disorders: a systematic
      review.
AB  - OBJECTIVE: The primary aim of this study is to conduct a systematic review in
      order to evaluate the use of sialendoscopy in treating pediatric salivary gland
      disorders. METHODS: Eligible articles were identified through a comprehensive
      search of electronic databases. Using predefined inclusion criteria, published
      articles on sialendoscopy in children were selected and reviewed. RESULTS: 17
      articles including 323 pediatric patients and 424 salivary glands managed by
      sialendoscopy were identified. The most common salivary gland disorder affected
      was the parotid (83% of cases), followed by the submandibular gland (16.5% of
      cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis
      followed by sialolithiasis (14.7%). The most common complication was ductal
      perforation. During a pooled mean follow-up time of 18.3 months, recurrences were
      reported in 14.5% of patients mostly in patients diagnosed with juvenile
      recurrent parotitis. CONCLUSION: Sialendoscopy is a minimally invasive diagnostic
      and therapeutic tool for inflammatory salivary gland disorders in pediatric
      patients. Based on the current review, sialendoscopy can be successfully
      implemented in cases of pediatric salivary gland disorders.

PMID- 29204919
TI  - Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified
      for HPV-status.
AB  - OBJECTIVE: Lymph node ratio (LNR) was shown to be a prognostic factor in
      laryngeal and oral cavity primaries. The purpose of this study was to investigate
      the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma
      (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR
      was evaluated as an additional predictive parameter to the 8th edition of AJCC
      TNM staging system. METHODS: From December 2009 to August 2015, patients
      diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively
      enrolled. After tumor resection with uni- or bilateral neck dissection, patients
      with >= 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis.
      RESULTS: 137 patients underwent tumor resection with uni- or bilateral neck
      dissection. The proportion of HPV-associated disease was 42%. Most patients (n =
      96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of
      pN + cases was significantly increased compared to p16-negative OPSCC (86% vs.
      58%, p = 0.007). Patients with LNR <= 10% had a significant better overall
      survival (OS) and disease-specific survival (DSS). However, when stratified for
      p16-status, LNR <= 10% had a significant impact on OS only for HPV-associated
      tumors (p = 0.027), whereas LNR of <= 10% was not a significant predictor for
      better OS in p16-negative OPSCC (p = 0.143). CONCLUSION: The LNR with a cut-off
      value of 10% serves as an additional prognostic parameter in HPV-related OPSCC
      and may help to improve risk stratification in combination with the revised AJCC
      8th edition TNM classification.

PMID- 29204920
TI  - Reply to the letter "Laryngopharyngeal reflux disease in the elderly".

PMID- 29204921
TI  - Reply to the Letter to the Editor concerning "Combined microscopic/endoscopic
      management of petrous apex lesions".

PMID- 29204923
TI  - Novel drug delivery systems, devices, and fabrication methods.

PMID- 29204922
TI  - Usefulness of our proposed olfactory scoring system during endoscopic sinus
      surgery in patients with chronic rhinosinusitis.
AB  - INTRODUCTION: The primary aim of the current study was to examine the usefulness
      of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients
      with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS).
      MATERIALS AND METHODS: Analyzed patients were divided into two groups: an
      eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T
      recognition threshold test was used to evaluate olfaction at baseline and at 3
      and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or
      12 months or with a decrease of >= 1.0 as compared with baseline were defined as
      showing clinical improvement. We scored mucosal conditions as normal (0 points),
      edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC),
      middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess
      during ESS. The total score of OCs (SOCs) was calculated (range 0-20 points). We
      compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory
      improvement were also investigated using uni- and multivariate analyses. RESULTS:
      SOCs in the ECRS and non-ECRS groups showed significant correlations with mean
      recognition thresholds at baseline and at 3 and 12 months. In the multivariate
      analysis for predicting improvement of mean recognition threshold, lower SOCs
      were significantly associated with olfactory improvement factors at 3 and 12
      months postoperatively in the ECRS group. CONCLUSION: SOCs appears promising for
      estimating olfactory prognosis after ESS in CRS patients.

PMID- 29204924
TI  - Efficacy of a bleomycin microneedle patch for the treatment of warts.
AB  - Warts are a common skin disease caused by infection of the human papilloma virus.
      Most treatments involving physical destruction of the infected cells, such as
      cryotherapy and electrocautery, are limited by intense pain, failure, or
      recurrences. Our aim was to compare the therapeutic effects of a newly developed
      bleomycin microneedle patch with cryotherapy in the treatment of warts. Forty-two
      patients with more than two wart lesions were included in the study. The two
      treatment modalities were randomly applied to different warts on each patient.
      Treatment efficacy was assessed using the Physician's Global Assessment (PGA) and
      the Patient's Global Assessment (PaGA). Mean PGA and PaGA scores were not
      significantly different between cryotherapy and bleomycin microneedle patch
      treatment. It was also determined that the mean size of all the warts treated
      with either modality shrank about equally at weeks 8 and 16 after initial
      treatment. Thus, treatment efficacy of the bleomycin microneedle patch was
      comparable to that of conventional cryotherapy. According to a visual analogue
      scale of pain, bleomycin microneedle patch treatment was significantly less
      painful than cryotherapy (p < .0001). In addition, use of the bleomycin
      microneedle patch was more tolerable for patients who were reluctant to receive
      the painful treatment. Thus, the bleomycin microneedle patch can be an effective,
      convenient, and innovative treatment modality for warts.

PMID- 29204925
TI  - Ultrasound-based triggered drug delivery to tumors.
AB  - Over the past few decades, applications of ultrasound (US) in drug delivery have
      been documented widely for local and site-specific release of bioactives in a
      controlled manner, after acceptable use in mild physical therapy for tendinitis
      and bursitis, and for high-energy applications in fibroid ablation, cataract
      removal, bone fracture healing, etc. US is a non-invasive, efficient, targetable
      and controllable technique. Drug delivery can be enhanced by applying directed US
      in terms of targeting and intracellular uptake. US cannot only provide local
      hyperthermia but can also enhance local extravasations and permeability of the
      cell membrane for delivery of cell-impermeable and poorly permeable drugs. It is
      also found to increase the anticancer efficacy of drug against solid tumors by
      facilitating uniform drug delivery throughout the tumor mass. This review
      summarizes the mechanism of US; various drug delivery systems like microbubbles,
      liposomes, and micelles; and biological manifestations employed for improving
      treatment of cancer, i.e., hyperthermia and enhanced extravasation. Safety issues
      are also discussed for better therapeutic outcomes of US-assisted drug delivery
      to tumors. This review can be a beneficial asset to the scientists looking at non
      invasive techniques (externally guided) for improving the anticancer potential of
      drug delivery systems.

PMID- 29204926
TI  - Alginate-liposomal construct for bupivacaine delivery and MSC function
      regulation.
AB  - Mesenchymal stromal cell (MSC) therapies have become potential treatment options
      for multiple ailments and traumatic injuries. In the clinical setting, MSC are
      likely to be co-administered with local anesthetics (LA) which have been shown to
      have dose- and potency-dependent detrimental effects on the viability and
      function of cells. We previously developed and characterized a sustained-release
      LA delivery formulation comprised of alginate-encapsulated liposomal bupivacaine.
      The current studies were designed to evaluate the effect of this formulation on
      the secretion of three key MSC regulatory molecules, interleukin 6 (IL-6),
      prostaglandin E2 (PGE2), and transforming growth factor-beta 1 (TGF-beta1). MSCs
      were treated with several bupivacaine formulations-bolus, liposome, or alginate
      liposome construct (engineered construct)-in the presence or absence of
      inflammatory stimulus to stimulate an injured tissue environment. Our results
      indicated that compared to bolus or liposomal bupivacaine, the engineered
      construct preserved or promoted MSC anti-inflammatory PGE2 secretion; however,
      the engineered construct did not increase TGF-beta1 secretion. Bupivacaine
      release profile analyses indicated that mode of drug delivery controlled the LA
      concentration over time and pathway analysis identified several shared and
      cytokine-specific molecular mediators for IL-6, PGE2, and TGF-beta1 which could
      explain differential MSC secretion responses in the presence of bupivacaine.
      Collectively, these studies support the potential utility of alginate
      encapsulated LA constructs for anti-inflammatory cell therapy co-administration
      and indicate that mode of local anesthetic delivery can significantly alter MSC
      secretome function.

PMID- 29204928
TI  - Brief Report: Factor Analysis of the Brazilian Version of the Adult Autism
      Spectrum Quotient.
AB  - This study examined the factor structure of the Brazilian version of the Autism
      Spectrum Quotient. This is a self-report questionnaire for continuous and
      quantitative assessment of autistic spectrum traits in adults. Confirmatory
      factor analysis was performed on the five-factor model (social skill, attention
      switching, attention to detail, communication and imagination) proposed by the
      original authors, support not being found for this model in our sample. An
      exploratory factor analysis was then performed that resulted in an alternative
      three-factor model (social skills, details/patterns and imagination).
      Confirmatory factor analysis of the latter model revealed adequate psychometric
      indexes. The Brazilian version of the AQ was shown to be an adequate instrument
      for the evaluation of signs compatible with the autism spectrum in adults.

PMID- 29204927
TI  - Augmented bioavailability of felodipine through an alpha-linolenic acid-based
      microemulsion.
AB  - The oral bioavailability of felodipine, a dihydropyridine calcium channel
      antagonist, is about 15%. This may be due to poor water solubility, and a lower
      intestinal permeability than a BCS class I drug, and hepatic first-pass
      metabolism of the drug. Many drugs are unpopular due to solubility issues. The
      goal of this study was to develop and optimize a felodipine-containing
      microemulsion to improve the intestinal permeability and bioavailability of the
      drug. The felodipine microemulsions were developed with the selected components,
      i.e., alpha-linolenic acid as the oil phase, Tween 80 as a surfactant, and
      isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for
      in vitro release and particle size. The optimized felodipine-loaded microemulsion
      was investigated for physicochemical interaction, surface morphology, intestinal
      permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic
      (electrocardiogram and heart rate variability), and pharmacokinetic studies to
      explore its suitability as a promising oral drug delivery system for the
      treatment of hypertension. The optimized felodipine-loaded microemulsion showed
      significantly higher (P < 0.05) apparent permeability coefficients (Papp) at
      7.918 * 10-5 cm/s after 1 h, when compared with conventional formulations that
      are marketed tablet, drug oily solution, and drug emulsion, which showed a
      maximum Papp of 3.013, 4.428, and 5.335 * 10-5 cm/s, respectively. The optimized
      felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity.
      Cellular uptake studies confirmed payload delivery to a cellular site on the
      J774.A1 cell line. The rheology study of the optimized felodipine-loaded
      microemulsion revealed Newtonian-type flow behavior and discontinuous
      microemulsion formation. In pharmacodynamic studies, significant differences in
      parameters were observed between the optimized felodipine-loaded microemulsion
      and marketed formulation. The optimized felodipine-loaded microemulsion showed
      significantly higher (p < 0.01) C max (7.12 +/- 1.04 MUg/ml) than marketed
      tablets (2.44 +/- 1.03 MUg/ml). It was found that AUClast obtained from the
      optimized felodipine-loaded microemulsion (84.53 +/- 10.73 MUg h/ml) was
      significantly higher (p < 0.01) than the marketed tablet (27.41 +/- 5.54 MUg
      h/ml). The relative bioavailability (Fr) of the optimized felodipine-loaded
      microemulsion was about 308.3% higher than that of the marketed formulation. The
      results demonstrate that the prepared microemulsion is an advanced and efficient
      oral delivery system of felodipine for the management of hypertension.

PMID- 29204929
TI  - What About the Girls? Sex-Based Differences in Autistic Traits and Adaptive
      Skills.
AB  - There is growing evidence of a camouflaging effect among females with autism
      spectrum disorder (ASD), particularly among those without intellectual
      disability, which may affect performance on gold-standard diagnostic measures.
      This study utilized an age- and IQ-matched sample of school-aged youth (n = 228)
      diagnosed with ASD to assess sex differences on the ADOS and ADI-R, parent
      reported autistic traits, and adaptive skills. Although females and males were
      rated similarly on gold-standard diagnostic measures overall, females with higher
      IQs were less likely to meet criteria on the ADI-R. Females were also found to be
      significantly more impaired on parent reported autistic traits and adaptive
      skills. Overall, the findings suggest that some autistic females may be missed by
      current diagnostic procedures.

PMID- 29204930
TI  - Double-layer carbon nanocapsules with radioiodine content and its interaction
      with calcium, phosphorus, and strontium.
AB  - First principles calculations have been performed for C60@C180 carbon double
      layer endofullerenes with up to: three diatomic radioiodine molecules (131I2),
      two potassium radio-iodide (K131I), and three sodium radio-iodide (Na131I)
      inside. The plane-wave pseudopotential (PP) method within the general gradient
      approximation (GGA) in the framework of the density functional theory (DFT) and
      time-dependent DFT (TD-DFT) was used to perform geometric optimizations (GOs) and
      molecular dynamics (MD) at 310 K and atmospheric pressure. We found that the
      double-layer carbon nanocapsules formed by two concentric fullerenes (C180
      surrounding C60) are very stable and may contain a radiodosis, without altering
      their configuration; that is, the 3(131I2)@C60@C180, 2(K131I)@C60@C180, and
      3(Na131I)@C60@C180 systems constitute stable nanocapsules. We analyzed the
      interaction of double-layer endofullerene with radioactive content with some
      calcium, phosphorus, and strontium atoms, [n(X131I)@C60@C180 + mY], for X = I, K,
      Na; Y = Ca, P, Sr; n = 1, 2, 3; m = 1, ..., 20. Our calculations show that up to
      m = 20 calcium atoms can easily be physisorbed by the outer surface of the double
      layer endofullerene, maintaining their integrity and shielding the radiodosis of
      any interaction that can proceed from the outside. It is thus concluded that
      these double-layer endofullerenes can be functionalized as vectors to deliver
      radiodosis with structural advantages over the single layer systems; as they are
      more robust, stable, and possess a larger surface to functionalize with some
      atoms serving as molecular recognizers. Graphical abstract Double-layer carbon
      nanocapsules with radioiodine content and its interaction with calcium,
      phosphorus and strontium.

PMID- 29204931
TI  - Dyslexie font does not benefit reading in children with or without dyslexia.
AB  - In two experiments, the claim was tested that the font "Dyslexie", specifically
      designed for people with dyslexia, eases reading performance of children with
      (and without) dyslexia. Three questions were investigated. (1) Does the Dyslexie
      font lead to faster and/or more accurate reading? (2) Do children have a
      preference for the Dyslexie font? And, (3) is font preference related to reading
      performance? In Experiment 1, children with dyslexia (n = 170) did not read text
      written in Dyslexie font faster or more accurately than in Arial font. The
      majority preferred reading in Arial and preference was not related to reading
      performance. In Experiment 2, children with (n = 102) and without dyslexia (n =
      45) read word lists in three different font types (Dyslexie, Arial, Times New
      Roman). Words written in Dyslexie font were not read faster or more accurately.
      Moreover, participants showed a preference for the fonts Arial and Times New
      Roman rather than Dyslexie, and again, preference was not related to reading
      performance. These experiments clearly justify the conclusion that the Dyslexie
      font neither benefits nor impedes the reading process of children with and
      without dyslexia.

PMID- 29204932
TI  - A retrospective cohort study of patients treated with anti-tuberculous therapy
      for presumed ocular tuberculosis.
AB  - BACKGROUND: Uveitis involving the posterior segment is a significant and
      potentially blinding condition. The diagnosis and treatment of patients with
      uveitis associated with tuberculosis remains controversial, and commonly,
      patients are systemically well. Use of the interferon-gamma release assays has
      added to the controversy, as the significance of a positive test may be
      uncertain. We aim to report the outcomes of anti-tuberculous treatment in a
      cohort of patients treated in Birmingham, for presumed "ocular tuberculosis",
      based on clinical findings, systemic assessment and specific testing for
      tuberculosis. RESULTS: We found that in our cohort of 41 patients treated between
      2010 and 2014, the majority achieved disease-free remission, even in cases where
      anti-tuberculous treatment was delayed. CONCLUSIONS: Despite controversy, this
      study strongly supports the use of anti-tuberculous therapy in such patients and
      highlights the need for formal prospective trials and treatment protocols.

PMID- 29204933
TI  - Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal
      cancer: real-life data from The Netherlands.
AB  - BACKGROUND: The RECOURSE trial showed clinical efficacy for
      trifluridine/tipiracil for refractory metastatic colorectal cancer patients. We
      assessed the feasibility and effectiveness of trifluridine/tipiracil in daily
      clinical practice in The Netherlands. METHODS: Medical records of patients from
      17 centers treated in the trifluridine/tipiracil compassionate use program were
      reviewed and checked for RECOURSE eligibility criteria. Baseline characteristics,
      safety, and survival times were compared, and prespecified baseline
      characteristics were tested in multivariate analyses for prognostic significance
      on overall survival (OS). RESULTS: A total of 136 patients with a median age of
      62 years were analyzed. Forty-three patients (32%) did not meet the RECOURSE
      eligibility criteria for not having received all prior standard treatments (n =
      35, 26%) and/or ECOG performance status (PS) 2 (n = 12, 9%). The most common
      grade >=3 toxicities were neutropenia (n = 44, 32%), leukopenia (n = 8, 6%),
      anemia (n = 7, 5%), and fatigue (n = 7, 5%). Median progression-free survival
      (PFS) and median OS were 2.1 (95% CI, 1.8-2.3) and 5.4 months (95% CI, 4.0-6.9),
      respectively. Patients with ECOG PS 2 had a worse median OS (3.2 months) compared
      to patients with ECOG PS 0-1 (5.9 months). ECOG PS, KRAS-mutation status, white
      blood cell count, serum lactate dehydrogenase, and alkaline phosphatase were
      prognostic factors for OS. CONCLUSIONS: Our data show that treatment with
      trifluridine/tipiracil in daily clinical practice is feasible and safe.
      Differences in patient characteristics between our population and the RECOURSE
      study population should be taken into account in the interpretation of survival
      data. Our results argue against the use of trifluridine/tipiracil in patients
      with ECOG PS 2. FUNDING: Johannes J.M. Kwakman received an unrestricted research
      grant from Servier.

PMID- 29204934
TI  - Preventive use of berberine in inhibition of lead-induced renal injury in rats.
AB  - The kidney is one of the main organs affected by lead toxicity. We investigated
      the effects of berberine on lead-induced nephrotoxicity in adult male Wistar
      rats. Animals received an aqueous solution of lead acetate (500 mg Pb/L in the
      drinking water) and/or berberine (50 mg/kg, i.g.) for 8 weeks. Lead caused an
      increase in malondialdehyde (P < 0.001) and total oxidant status (P < 0.01), and
      a decrease in reduced glutathione (P < 0.001), catalase (P < 0.01), superoxide
      dismutase (P < 0.001), and total antioxidant capacity (P < 0.05). Berberine
      prevented the prooxidant and antioxidant imbalance induced by lead (P < 0.001).
      Berberine corrected the increased relative kidney weight (P < 0.05) and
      biomarkers of renal function (creatinine (P < 0.001), urea (P < 0.05), uric acid
      (P < 0.001), albumin (P < 0.01), and total protein (P < 0.05)) in lead group. It
      also attenuated lead-induced abnormal renal structure. The results confirmed
      renoprotective effects of berberine in an animal model of lead-induced
      nephrotoxicity by molecular, biochemical, and histopathological analysis through
      inhibiting lipid peroxidation and enhancing antioxidant defense system
      mechanisms. Therefore, berberine makes a good candidate to protect against the
      deleterious effect of chronic lead intoxication.

PMID- 29204935
TI  - Neuroprotective potential of crocin against malathion-induced motor deficit and
      neurochemical alterations in rats.
AB  - In several epidemiological studies, an association between pesticide exposure and
      the incidence of Parkinson's disease (PD) has been reported. Increasing evidence
      showed that oxidative stress plays an important role in the pathogenesis of PD.
      The present study investigated the preventive effect of crocin, saffron active
      components, on malathion (an organophosphate pesticide (OP))-induced Parkinson
      like behaviors in rat. Rats were divided into eight groups: control (normal
      saline), malathion (100 mg/kg/day, i.p), crocin (10, 20, or 40 mg/kg/day, i.p)
      plus malathion, levodopa (10 mg/kg/day, i.p) plus malathion, crocin (40
      mg/kg/day, i.p), and PEG (vehicle of levodopa) groups. Treatments were continued
      for 28 days. The neurobehavioral tests which include open field, rotarod and
      catalepsy were performed on day 28. The activity of acetylcholinesterase (AChE)
      in serum, the levels of malondialdehyde (MDA), reduced glutathione (GSH), TNF
      alpha, and IL-6 in striatum at the end of treatments were evaluated. Results
      showed that malathion induced neurobehavioral impairments together with elevation
      of MDA, TNF-alpha and IL-6 levels, reduction of GSH, and AChE activity. Crocin
      (10, 20, and 40 mg/kg) improved neurobehavioral impairments induced by malathion
      but not AChE activity. Crocin (10, 20, and 40 mg/kg) or levodopa plus malathion
      decreased MDA and increased GSH. Also crocin (10 mg/kg) decreased TNF-alpha and
      IL-6 levels in striatum. In summary, subchronic malathion exposure induced
      Parkinson-like behavior in rat. Crocin exhibited protective effects against
      malathion-induced Parkinson-like behavior through reducing lipid peroxidation,
      improvement of motor deficit and anti-inflammatory effects.

PMID- 29204936
TI  - Analysis method for PCBs in reclaimed oil using a fast-GC triple stage quadrupole
      mass spectrometer with the 13-component quantitation method.
AB  - It is necessary for companies supplying reclaimed oil to analyze polychlorinated
      biphenyls (PCBs), because there is a possibility of the presence of contaminants
      due to trace-level PCBs in the reclaimed oil. However, common analysis methods of
      PCBs are time-consuming and complicated. Fast-GC triple stage quadrupole mass
      spectrometer with the 13-component quantitation method is an official method for
      analyzing PCBs in insulating oil in Japan. This method is extremely fast and
      simplified. The purpose of this study involves an investigation of the
      aforementioned fast and simple method for potential use in the analysis of
      reclaimed oil. Furthermore, it was attempted to combine the method with sample
      preparation involving only hexane dilution. The effect of sample dilutions
      corresponding to 100, 300, and 500 times was evaluated for reducing the matrix
      effect. The matrix effect was suppressed at a dilution ratio equal to or
      exceeding 300 times. Calibration curves of four points, namely 0.01, 0.05, 0.1,
      and 0.5 ng/mL, (ignored origin) by using an internal standard method were
      prepared for the 13 components. The square of regression coefficient (R2) values
      of all calibration curves exceeded 0.997. This method was adopted for the
      analysis of reclaimed oil containing 0.5 MUg/mL PCBs, which corresponds to the
      judgment criteria, and accurate quantitation (accuracy value, 94.0-102%) and good
      repeatability (%RSD, 3.6%) were obtained. Furthermore, the required sensitivity
      was maintained even when 800 samples were analyzed without a cleaning ion source
      and an exchanging analysis column.

PMID- 29204937
TI  - Determination and environmental risk assessment of synthetic musks in the water
      and sediments of the Jiaozhou Bay wetland, China.
AB  - Human activity in estuarine areas has resulted in pollution of the aquatic
      environment, but little is known about the levels of synthetic musks (SMs) in
      river water and sediments in estuarine areas. This study investigated the
      concentrations and distribution of SMs in the Jiaozhou Bay wetland, including
      celestolide, phantolide, traseolide, galaxolide (HHCB), tonalide (AHTN), musk
      xylene and musk ketone (MK). The SMs HHCB, AHTN and MK were detected at
      concentrations of 10.7-208, not detected (ND)-59.2 and ND-13.6 ng/L,
      respectively, in surface water samples and 13.1-27.3, 3.06-14.5 and 1.33-18.8
      ng/g (dry weight; dw), respectively, in sediment samples. Based on the calculated
      total organic carbon (TOC) concentrations, there was no significant correlation
      between SMs and TOC in sediment samples (p > 0.05). The hazard quotients were
      0.204, 0.386 and 0.059 for AHTN, HHCB and MK, respectively, which indicated no
      serious environmental impact, because these values are all less than 1. The
      concentrations of SMs decreased as the distance to the Xiaojianxi refuse landfill
      increased in both surface water and sediments. Compared with previous studies,
      the concentration of SMs in the Jiaozhou Bay wetland was relatively high.
      Therefore, more attention should be paid to SMs because of their persistent
      impact on human health and the environment.

PMID- 29204939
TI  - Toxic effects of linear alkylbenzene sulfonate on Chara vulgaris L.
AB  - Linear alkylbenzene sulfonate (LAS) is a common organic pollutant in freshwater
      environments. Studies have shown that the toxicity of LAS to aquatic plants is
      directly related to the LAS concentration and depends on the plant species. A 2
      week exposure experiment was designed to investigate the toxicity of LAS for the
      submerged plant Chara vulgaris L. and focused on the effects on growth,
      photosynthetic pigment content, and antioxidant enzyme activity. The results
      showed that when exposed to lower LAS doses (<= 1.0 mg l-1), the dry weight of C.
      vulgaris was significantly reduced. Compared to those of the control group,
      superoxide dismutase (SOD) and peroxidase (POD) activities significantly
      increased, while no significant effect was observed for catalase (CAT) activity.
      Malondialdehyde (MDA) content significantly increased in the LAS treatment groups
      except for the LAS concentration of 1.0 mg l-1. The content of carotenoids was
      significantly lower in plant groups exposed to lower concentrations of LAS, while
      carotenoid content significantly increased at the highest concentration of LAS
      (5.0 mg l-1). LAS treatment did not significantly affect chlorophyll a and b or
      total chlorophyll content. The results showed that 5.0 mg l-1 causes some
      oxidative damage to C. vulgaris but that this concentration was far below the
      lethal concentration of LAS to C. vulgaris and did not produce severe effects on
      growth. C. vulgaris plants had some resistance to LAS stress (in the group with
      <= 5.0 mg l-1). SOD, POD, and carotenoids were more sensitive to the effects of
      LAS stress and may be considered as response indicators for LAS stress.

PMID- 29204938
TI  - Preparation of Fe-Cu-kaolinite for catalytic wet peroxide oxidation of 4
      chlorophenol.
AB  - Fe-Cu-kaolinites were prepared by co-precipitation and hydrothermal methods, and
      characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM),
      where 2 wt.% natural kaolinite was dispersed, and the ratios of (Al + Fe +
      Cu)/clay = 10 mmol/g and Al/(Fe + Cu) = 5/1 were maintained. The effect of
      different drying methods (vacuum drying, ethanol exchange drying, freeze-drying,
      microwave drying, normal oven drying) and different Fe/Cu molar ratio (0/2,
      0.4/1.6, 0.8/1.2, 1/1, 1.2/0.8, 1.6/0.4, 2/0) was also assessed. Catalytic wet
      peroxide oxidation (CWPO) reaction of 4-chlorophenol (4-CP) was used to probe the
      reactivity and activity of the materials prepared. The results showed that Fe and
      Cu could be successfully intercalated into the interlayer of kaolinite by
      hydrothermal method, where specific surface area and pore volume increased by 19
      times and 7 times, respectively; the intensity of basal space (001) reflection
      peak was reduced by 80%, and tip width was doubly increased. The catalyst
      possessed higher reactivity, with 85.5% of 4-CP conversion being observed,
      whereas only 15.2% of 4-CP was removed over raw kaolinite. High-power microwave
      drying (720 W) was the best drying method, because it resulted in greater
      microstructure and thus higher reactivity (85.3% of 4-CP conversion), with lower
      active metal (Fe or Cu) leaching (3.96 mg L-1). Fe/Cu molar ratio of 0.8-1.0/1.2
      1.0 was considered as the optimum ratio in pillaring solution, for maintaining
      higher catalytic activity (85-90% of 4-CP conversion) and lower metal (Fe or Cu)
      leaching (7-9.3 mg L-1).

PMID- 29204940
TI  - Isolation of monocrotophos-degrading strain Sphingobiumsp. YW16 and cloning of
      its TnopdA.
AB  - The bacterial strain Sphingobium sp. YW16, which is capable of degrading
      monocrotophos, was isolated from paddy soil in China. Strain YW16 could hydrolyze
      monocrotophos to dimethylphosphate and N-methylacetoacetamide and utilize
      dimethylphosphate as the sole carbon source but could not utilize N
      methylacetoacetamide. Strain YW16 also had the ability to hydrolyze other
      organophosphate pesticides. A fragment (7067 bp) that included the
      organophosphorus hydrolase gene, opdA, was acquired from strain YW16 using the
      shotgun technique combined with SEFA-PCR. Its sequence illustrated that opdA was
      included in TnopdA, which consisted of a transpose gene, a putative integrase
      gene, a putative ATP-binding protein gene, and opdA. Additionally, a conjugal
      transfer protein gene, traI, was located downstream of TnopdA. The juxtaposition
      of TnopdA with TraI suggests that opdA may be transferred from strain YW16 to
      other bacteria through conjugation. OpdA was able to hydrolyze a wide range of
      organophosphate pesticides, with the hydrolysis efficiency decreasing as follows:
      methyl parathion > fenitrothion > phoxim > dichlorvos > ethyl parathion >
      trichlorfon > triazophos > chlorpyrifos > monocrotophos > diazinon. This work
      provides the first report of opdA in the genus Sphingobium.

PMID- 29204941
TI  - Temporal dynamics of total and free-living nitrogen-fixing bacterial community
      abundance and structure in soil with and without history of arsenic contamination
      during a rice growing season.
AB  - Despite the fact that the nitrogen (N) fixers act as the key regulator of
      ecosystem process, a detailed study of their abundance, diversity, and dynamics
      in arsenic (As)-contaminated rice fields is missing so far. DNA extracted from
      soil followed by 16S rRNA and nifH gene-based real-time qPCR, clone library
      analysis, and DNA sequencing were used to examine the status of the total and
      diazotrophic communities in two agricultural fields with and without arsenic
      contamination history during one rice cultivation season. In general, higher nifH
      and 16S rRNA gene copy numbers were observed in rice growing soils with lesser As
      than that with higher As. Elevated levels of 16S rRNA and nifH genes in soil is
      directly associated with total and nitrogen fixers abundance in the agricultural
      land without As contamination history through the cultivation period, but the
      copy number of 16S rRNA gene was decreased, and the nifH gene remained unchanged
      in the As-contaminated land. Additionally, Canonical Correspondence Analysis
      (CCA) indicated the possible suppression of nifH gene abundance by soil pH,
      phosphate, and As content. Increased abundance of total and Acidobacterial
      lineages in low As-containing soil and the detection of several uncultured groups
      among nifH gene sequence in higher frequency indicated the presence of novel nifH
      bearing bacterial groups. Conversely, the abundance of copiotrophic
      Proteobacterial lineages gradually increased in soil with higher As. Herein, our
      study demonstrated that the dynamics of free-living nitrogen-fixing bacterial
      communities were perturbed due to As contamination in agricultural land.

PMID- 29204942
TI  - Spectrum of health condition in methyl isocyanate (MIC)-exposed survivors
      measured after 30 years of disaster.
AB  - Health effects of methyl isocyanate (MIC) exposure were mostly reported on the
      one-time acute exposure in Bhopal population. Epidemiological survey conducted by
      the Indian apex body of health research has been reported as Technical Reports,
      which were lacking in peer review by the expert epidemiologic scientists. The
      present pilot survey was aimed to measure the health effects 30 years post
      disaster in MIC-exposed survivors. Questionnaire-based survey has captured every
      health complaint in 168 individuals and grouped as systemic functions for
      interpreting the long-term effects of MIC. Key health parameters, including
      reproductive outcome and respiratory/orthopedic/general morbidity, were prevalent
      among the severely exposed population compared to control and moderately exposed
      groups. The collective incidence of diabetes, hypertension, and cancer also was
      prevalent in the severely exposed group. Ophthalmic morbidity was almost similar
      in the three groups, rather with higher incidence in the control group, though
      not statistically significant. Among all health parameters, reproductive,
      ophthalmic, and respiratory effects were prevalent over others. Although the
      incidence of health problems has been declined among the survivors, long-term
      effect is apparent as scars of one-time acute exposure might trigger sequel of
      long-term effects. Additionally, acquisition of genetic rearrangements, survival
      of T cell sub-populations, variable latency of chemical effect on DNA
      nucleosides, nutritional status, occupational exposure, living environment,
      lifestyle, and overall gene-environment interaction might perturb individual
      immunity and favor onset of long-term illness in a scenario of background
      exposure to MIC. However, the exercise should be continued on a larger sample
      size for drawing a conclusive result on long-term MIC effect on survivors'
      health.

PMID- 29204943
TI  - Occurrence, distribution and composition of aliphatic and polycyclic aromatic
      hydrocarbons in sediment cores from the Lower Fox River, Wisconsin, US.
AB  - The Lower Fox River is a 39 mile section which supports approximately 270,000
      rural inhabitants across 18 counties, 303,000 metropolitan residents in Green Bay
      and Appleton, Wisconsin, and several large industrial complexes such as paper
      mills and power plants. This paper presents the distribution and concentrations
      of aliphatic (n-alkanes) and aromatic hydrocarbons (polycyclic aromatic
      hydrocarbons [PAHs]) as well as total organic carbon (TOC) in the Lower Fox River
      to identify the sources of hydrocarbon contamination. Excluding one outlier,
      percent TOC values were between 0.73 and 19.9% with an average value of 6.74%.
      Total n-alkanes ranged from 3.51 MUg/g to 117 MUg/g and showed a strong presence
      of odd carbon-numbered n-alkane ratios (range of C25 to C35), suggesting source
      input from terrestrial biomass. The mean polycyclic aromatic hydrocarbon (PAH)
      concentration was 24,800 ng/g. High molecular weight PAH concentrations dominated
      the distribution of hydrocarbon contaminants. Cross-plots of PAHs were used to
      compare diagnostic source ratios of benz[a]anthracene (BaA), chrysene (Chr),
      fluoranthene (Flu), pyrene (Pyr), anthracene (Ant), phenanthrene (Phe),
      indeno[1,2,3-cd]pyrene (InP), and benzo[g,h,i]perylene (BghiP) by depth and area.
      PAH ratios varied slightly with the core depth. Deeper core sections indicated
      the presence of biomass combustion while the upper core sections indicated
      combustion of both petroleum and biomass. The PAH toxicity of one core was
      estimated using toxicity equivalency factors, and the benzo[a]pyrene toxic
      equivalence quotient totaled 2,293 ng/g-dry wt. Levels of PAHs in sediments are
      compared with established regulatory values and recommendations are made.

PMID- 29204944
TI  - Comparison of culture media indicates a role for autologous serum in enhancing
      phenotypic preservation of rabbit limbal stem cells in explant culture.
AB  - In this study, we aimed to compare the effects of six different cell culture
      media and autologous serum (AS) on the phenotypic characteristics of rabbit
      limbal epithelial stem cells (LESC) cultivated on porous polyethylene
      terephthalate (PET) membranes. Limbal explants from rabbit corneas were grown on
      PET membrane inserts in five different media: DMEM-F12 with fetal bovine serum
      (FBS) (DMEM-F12-FBS), with pluripotin (DMEM-F12-pluripotin) and with autologous
      serum (DMEM-F12-AS), Epilife, Keratinocyte Serum Free Medium (KSFM) and Defined
      Keratinocyte Serum Free Medium. The effects of different media were evaluated by
      total cell yield from explants, measuring the expression of proteins by
      immunofluorescence and gene expression by Real Time PCR. In all five media
      tested, most of the limbal epithelial cells (LEC) which proliferated from
      explants were positive for cytokeratin (CK) 14 (85-90%), indicating that all five
      media support the growth of LESC from explants. The expression of differentiation
      markers; CK 3 and 12 was highest in DMEM-F12-FBS (56%), was lower in Epilife and
      KSFM (26 and 19%, respectively), with the lowest values (13%) obtained in DMEM
      F12-AS. Gene expression of limbal cultures on PET membrane inserts was compared
      to fresh limbal tissue. In DMEM-F12-FBS, DMEM-F12-pluripotin, and DMEM-F12-AS,
      expression of potential LESC markers CXCR4 and polycomb complex protein BMI-1
      were similar to limbal tissue. DMEM-F12 with 10% AS maintained a higher
      percentage of potential stem cell marker genes and lower expression of genes
      involved in differentiation compared to Epilife or KSFM. Our study shows that
      rabbit LEC can be cultivated on PET inserts using DMEM-F12 with autologous serum
      without a requirement for amniotic membrane or feeder cells.

PMID- 29204946
TI  - Gene editing using CRISPR/Cas9: implications for dual-use and biosecurity.

PMID- 29204945
TI  - D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity
      rankings, and relative binding free energies.
AB  - The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September
      2016 through February 2017. This challenge was based on a dataset of structures
      and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed
      by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six
      orders of magnitude, and 36 high-resolution co-crystal structures with
      representatives of four major ligand classes. Strong global participation was
      evident, with 49 participants submitting 262 prediction submission packages in
      total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1
      subchallenge testing ligand pose prediction methods and ranking and scoring
      methods, and a Stage 2 subchallenge testing only ligand ranking and scoring
      methods after the release of all blinded co-crystal structures. Two smaller
      curated sets of 18 and 15 ligands were developed to test alchemical free energy
      methods. This overview summarizes all aspects of GC2, including the dataset
      details, challenge procedures, and participant results. We also consider
      implications for progress in the field, while highlighting methodological areas
      that merit continued development. Similar to GC2015, the outcome of GC2
      underscores the pressing need for methods development in pose prediction,
      particularly for ligand scaffolds not currently represented in the Protein Data
      Bank ( http://www.pdb.org ), and in affinity ranking and scoring of bound
      ligands.

PMID- 29204948
TI  - Phase Transitions in a Logistic Metapopulation Model with Nonlocal Interactions.
AB  - The presence of one or more species at some spatial locations but not others is a
      central matter in ecology. This phenomenon is related to ecological pattern
      formation. Nonlocal interactions can be considered as one of the mechanisms
      causing such a phenomenon. We propose a single-species, continuous time
      metapopulation model taking nonlocal interactions into account. Discrete
      probability kernels are used to model these interactions in a patchy environment.
      A linear stability analysis of the model shows that solutions to this equation
      exhibit pattern formation if the dispersal rate of the species is sufficiently
      small and the discrete interaction kernel satisfies certain conditions. We
      numerically observe that traveling and stationary wave-type patterns arise near
      critical dispersal rate. We use weakly nonlinear analysis to better understand
      the behavior of formed patterns. We show that observed patterns arise through
      both supercritical and subcritical bifurcations from spatially homogeneous steady
      state. Moreover, we observe that as the dispersal rate decreases, amplitude of
      the patterns increases. For discontinuous transitions to instability, we also
      show that there exists a threshold for the amplitude of the initial condition,
      above which pattern formation is observed.

PMID- 29204947
TI  - Improved Sp1 and Betaine Homocysteine-S-Methyltransferase Expression and
      Homocysteine Clearance Are Involved in the Effects of Zinc on Oxidative Stress in
      High-Fat-Diet-Pretreated Mice.
AB  - Zinc plays a role in alleviating oxidative stress. However, the related
      mechanisms remain to be further elucidated. The present study was conducted to
      investigate whether the recovery of oxidative stress in high-fat-diet (HFD)
      pretreated mice was affected by zinc. Male mice received either an HFD or a low
      fat-diet (LFD) for 8 weeks. Then, the mice fed with HFD and LFD were both
      assigned to either a control diet (30 mg zinc, ZD) or a no-added zinc diet (NZD)
      for an additional 4 weeks. The results showed that after feeding with NZD for 4
      weeks, the HFD-pretreated mice had the highest plasma glucose and insulin
      concentrations, while had the lowest CuZn-SOD and glutathione concentrations.
      Moreover, after feeding with NZD for 4 weeks, the HFD-pretreated mice had the
      highest hepatic ROS and homocysteine concentrations, while had the lowest
      glutathione and methionine concentrations. Furthermore, the HFD-pretreated mice
      fed with NZD for 4 weeks had the lowest gene and protein expression of betaine
      homocysteine-S-methyltransferase (BHMT), cystathionine beta-synthase, and Sp1.
      The results suggested that zinc was critical for oxidative stress alleviation and
      homocysteine clearance in HFD-pretreated mice. It was further elucidated that
      improved Sp1 and BHMT expression are involved in the effects of zinc on oxidative
      stress.

PMID- 29204949
TI  - [Stroke prevention in atrial fibrillation in Germany. Situational analysis of
      treatment reality based on retrospective data].
AB  - BACKGROUND: Guideline-based, risk-adjusted therapy with anticoagulants reduce
      thromboembolic stroke risk in patients with atrial fibrillation (AF). METHOD:
      This study analyzed use of oral anticoagulation in German AF-patients. Access to
      anonymized patient records was made via IMS Health Disease Analyzer database
      (sample size: 113,619 patients with ICD-10 Code I48.-; observation period:
      11/2010-10/2013). Results were subsequently extrapolated to all general
      practitioners' (GPs) and cardiological practices in Germany. RESULTS: In 2011 12
      month AF-prevalence was extrapolated to 2.1 million patients (first diagnosed: n
      = 537.548). In 2012 AF-prevalence gone up to 2.2 million cases (first diagnosed:
      n = 537.548) and in 2013 to 2.8 million (first diagnosed: n = 636.571). Commonly
      prescribed oral anticoagulants (OAC) were vitamin K antagonists (VKA). Unstable
      INR setting, private health insurance, hospital admission, heart failure or
      hypertension increased probability of change from VKA to non-vitamin K antagonist
      oral anticoagulants (NOAC). 17.3-36.5% of patients with CHA2DS2-VASc-score >= 2
      did not receive any thromboembolism prophylaxis; 38.5% with CHA2DS2-VASc-score =
      0 received unnecessarily OACs. For 2013 a potential of 29.749 ischemic strokes in
      GP practices was calculated, which possibly can be avoided by thromboembolism
      prophylaxis according to guidelines. CONCLUSIONS: Risk-based anticoagulation
      showed requirements for optimization. Use of OACs, according to guideline
      recommendations, would minimize bleeding risks, reduce ischemic strokes and could
      release resources.

PMID- 29204950
TI  - [Physiotherapy in pain medicine. Further treatment after a multimodal pain
      therapy program].
AB  - BACKGROUND: Chronic pain is a global health challenge for both the individual
      patient and the healthcare community. Multimodal Pain Management, as one of the
      possible therapies for patients with chronic pain, provides a comprehensive tool
      that places equally high demands on therapists and patients and is consistently
      recommended. METHOD: In a monocentric cross-sectional study, patients who had
      previously participated in a multi-modal pain therapy program lasting several
      weeks were asked about the follow-up recommendations of the interdisciplinary
      team of the Pain Management Clinic. Using a structured questionnaire, patients
      should indicate whether they were treated on an outpatient basis after discharge,
      or for what reasons they were not. RESULTS: 80 patients were randomized to the
      survey, 47 of whom participated in the survey (33 women, mean age 60 +/- 14.5
      years, 14 men, 56 +/- 11.9 years). The follow-up recommendations of the
      interdisciplinary team were implemented by 70% of the participants. Pain
      management strategies (68%), relaxation methods (53%) and moderate endurance
      sports (32%) were the most frequently used. 28 patients (60%) continued to
      receive physiotherapy after the pain therapy program. 19 patients (40%) did not
      continue physiotherapy after discharge. The reasons for this were lack of medical
      prescription (32%), dissatisfaction with treatment (17%) and inadequate treatment
      (15%). Lack of time due to caring for a family member or childcare (working and
      single mothers) was reported by 10% of patients. CONCLUSIONS: There is currently
      no adequate, outpatient, continuing care in the sense of a multimodal treatment
      concept for chronic pain patients. The needs of patient preferences are not
      sufficiently considered. Deficits lie in the practice organization and health
      care structures, which continue the multimodal idea.

PMID- 29204951
TI  - [Real-life efficacy and tolerability of methocarbamol in patients suffering from
      refractory muscle-related low/back pain - Results of a health care research
      project based on data from the German pain practice registry].
AB  - BACKGROUND: Subacute, muscle-related low/back pain (L/BP) is known to be
      difficult to treat and frequently requires more specific causal-oriented
      treatments with agents improving the increased muscle tone. Currently, only
      methocarbamol is approved and available for the 1st-line treatment of patients
      with muscle-related L/BP in Germany - however, without sufficient data on longer
      lasting effects (> 1 week) in elsewhere refractory patients. METHOD:
      Noninterventional cohort study, based on anonymized routine data of the German
      pain practice registry; retrospective evaluation of patients with refractory
      L/BP, who first time received a treatment with methocarbamol between October 1st
      until December 31st, 2015, and who documented their response to treatment with
      the standardized and validated instruments of the German pain questionnaire over
      at least 4 weeks (n = 251 patients). RESULTS: During the 4-week evaluation
      period, patients reported a highly significant and clinically relevant
      improvement of pain intensity (from 53.0 +/- 10.5 to 19.0 +/- 10.0 mm VAS), pain
      related disability in daily life (mPDI: from 42.1 +/- 12.5 to 15.5 +/- 10.8) and
      quality of life (QLIP: from 18.6 +/- 6.3 to 34.0 +/- 5.5; all changes p < 0.001
      vs. baseline). Corresponding 50% response rates were 81.7 (n = 205), 68.5 (n =
      172) und 91.6 (n = 230) %. In parallel, lumbar mobility (measured with the
      Schober's test) improved from 10.7 +/- 0.7 to 14.7 +/- 0.7 cm (p < 0,001).
      Overall, seven patients recorded eight minor treatment-related adverse events,
      which all resolved spontaneously during treatment without any specific
      countermeasures. CONCLUSION: Under the conditions of daily life, patients with
      elsewhere refractory L/BP reported a significant and clinically relevant
      improvement of pain intensity, pain-related disability and quality of life in
      response to a 4-week treatment with methocarbamol.

PMID- 29204952
TI  - [Therapeutic modulation of intestinal microbiota in irritable bowel syndrome.
      From probiotics to fecal microbiota therapy].
AB  - BACKGROUND: An abnormal intestinal microbiota (dysbiosis) plays a central role in
      the pathogenesis of the irritable bowel syndrome. METHOD: An overview of four
      current options for the treatment of irritable bowel syndrome, which are
      characterized by modulation of intestinal microbiota, is given. RESULTS AND
      CONCLUSIONS: Probiotics have very different effects on the individual symptoms of
      the irritable bowel. The choice of the appropriate preparation should therefore
      be based on the clinical symptomatology. The antibiotic rifaximin is effective in
      selected patients. Some patients also benefit from the repetition of this
      therapy. A FODMAP-reduced diet has shown significant alleviation of irritable
      bowel symptoms in studies. The fecal microbiota therapy (FMT) is a promising
      treatment option. At present, however, there are no such placebo-controlled
      studies to assess the effectiveness of this method.

PMID- 29204953
TI  - Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long
      Term Extension and Post-marketing Treatment.
AB  - Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive
      treatment of refractory focal onset seizures during the past 10 years. Long-term
      efficacy and safety of the drugs were demonstrated in large extension studies and
      in reports of subgroups of patients not studied in pivotal trials. Reviewing
      extension study and post-marketing outcome series for the four newer AEDs
      lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide
      clinicians in treating and monitoring patients. AED extension studies evaluate
      treatment retention, drug tolerability, and drug safety during individualized
      treatment with flexible dosing and thus provide information not available in
      rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1
      year and from 36 to 68% at 2-year treatment intervals. Safety findings were
      generally similar to those of pivotal trials, with no major safety risks
      identified and with several specific adverse drug effects, such as hyponatremia,
      reported. The third-generation AEDs, some through new mechanisms and others with
      improved tolerability compared to related AEDs, provide new options in efficacy
      and tolerability.

PMID- 29204954
TI  - Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety,
      Depression, and Cognitive Impairment.
AB  - Poststroke depression (PSD) is a common outcome of stroke that limits recovery
      and is only partially responsive to chronic antidepressant treatment. In order to
      elucidate changes in the cortical-limbic circuitry associated with PSD and its
      treatment, we examined a novel mouse model of persistent PSD. Focal endothelin-1
      induced ischemia of the left medial prefrontal cortex (mPFC) in male C57BL6 mice
      resulted in a chronic anxiety and depression phenotype. Here, we show severe
      cognitive impairment in spatial learning and memory in the stroke mice. The
      behavioral and cognitive phenotypes were reversed by chronic (4-week) treatment
      with fluoxetine, alone or with voluntary exercise (free-running wheel), but not
      by exercise alone. To assess chronic cellular activation, FosB+ cells were co
      labeled for markers of glutamate/pyramidal (VGluT1-3/CaMKIIalpha), gamma
      aminobutyric acid (GAD67), and serotonin (TPH). At 6 weeks poststroke versus sham
      (or 4 days poststroke), left mPFC stroke induced widespread FosB activation, more
      on the right (contralesional) than on the left side. Stroke activated glutamate
      cells of the mPFC, nucleus accumbens, amygdala, hippocampus, and raphe serotonin
      neurons. Chronic fluoxetine balanced bilateral neuronal activity, reducing total
      FosB and FosB/CamKII+ cells (mPFC, nucleus accumbens), and unlike exercise,
      increasing FosB/GAD67+ cells (septum, amygdala) or both (hippocampus, raphe). In
      summary, chronic antidepressant but not exercise mediates recovery in this
      unilateral ischemic PSD model that is associated with region-specific reversal of
      stroke-induced pyramidal cell hyperactivity and increase in gamma-aminobutyric
      acidergic activity. Targeted brain stimulation to restore brain activity could
      provide a rational approach for treating clinical PSD.

PMID- 29204957
TI  - Literature alert.

PMID- 29204956
TI  - Web alert.

PMID- 29204958
TI  - Pharmacokinetics and Safety of Ingenol Disoxate Gel Administered Under Maximum
      Use Conditions to Patients With Actinic Keratosis.
AB  - BACKGROUND AND OBJECTIVES: Ingenol disoxate (LEO 43204) is a field therapy in
      development for the treatment of actinic keratosis (AK) on areas between 25 and
      250 cm2. We evaluated the systemic exposure and safety of ingenol disoxate under
      maximum-use conditions. METHODS: This was a phase I, open-label, non-randomized,
      multicenter trial. Patients >= 18 years of age with >= 15 clinically typical,
      visible, discrete AK lesions in a treatment area on the full face or
      approximately 250 cm2 on the arm or scalp were treated once-daily for 3
      consecutive days with ingenol disoxate 0.018, 0.1, or 0.037% gel, respectively.
      RESULTS: The trial included 58 patients. Median age (range) of patients was 68
      years (42-89) [face, N = 18], 66 years (43-88) [arm, N = 21], and 67 years (37
      83) [scalp, N = 19]. The highest quantifiable ingenol disoxate level was observed
      in the arm group (0.33 nM, area under the concentration-time curve from time zero
      to the last data point [AUCtlast] 3.12 nM.h). Mean composite local skin response
      scores peaked at Day 4 and declined towards baseline by Day 15 in all treatment
      groups. Most adverse events (AEs) were of mild or moderate intensity; the most
      common treatment-related AEs were application-site pain (face, 88.9%; arm, 57.1%;
      scalp, 100.0%) and application-site pruritus (face, 50.0%; arm, 52.4%; scalp,
      42.1%). CONCLUSION: Very low systemic exposure to ingenol disoxate was observed
      when applied to the face, arm, or scalp in patients with AK under maximum-use
      conditions. No new safety signals were identified. TRIAL REGISTRATION:
      NCT02424305.

PMID- 29204955
TI  - The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple
      Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central
      nervous system with unknown etiology. Recently, the gut microbiota has emerged as
      a potential factor in the development of MS, with a number of studies having
      shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the
      host remain healthy by regulating various functions, including food metabolism,
      energy homeostasis, maintenance of the intestinal barrier, inhibition of
      colonization by pathogenic organisms, and shaping of both mucosal and systemic
      immune responses. Alteration of the gut microbiota, and subsequent changes in its
      metabolic network that perturb this homeostasis, may lead to intestinal and
      systemic disorders such as MS. Here we discuss the findings of recent MS
      microbiome studies and potential mechanisms through which gut microbiota can
      predispose to, or protect against, MS. These findings highlight the need of an
      improved understanding of the interactions between the microbiota and host for
      developing therapies based on gut commensals with which to treat MS.

PMID- 29204960
TI  - Seizures in Alzheimer's disease: is there more beneath the surface?

PMID- 29204959
TI  - Insights into the bisphosphonate holiday: a preliminary FTIRI study.
AB  - : Bone composition evaluated by FTIRI analysis of iliac crest biopsies from post
      menopausal women treated with alendronate for 10 years, continuously or
      alendronate for 5 years, followed by a 5-year alendronate-holiday, only differed
      with the discontinued biopsies having increased cortical crystallinity and
      heterogeneity of acid phosphate substitution and decreased trabecular
      crystallinity heterogeneity. INTRODUCTION: Bisphosphonates (BP) are the most
      commonly used and effective drugs to prevent fragility fractures; however,
      concerns exist that prolonged use may lead to adverse events. Recent
      recommendations suggest consideration of a BP "holiday" in individuals taking
      long-term BP therapy not at high risk of fracture. Data supporting or refuting
      this recommendation based on bone quality are limited. We hypothesized that a
      "holiday" of 5 years would cause no major bone compositional changes. METHODS: We
      analyzed the 31 available biopsies from the FLEX-Long-term Extension of FIT
      (Fracture Intervention Trial) using Fourier transform infrared imaging (FTIRI).
      Biopsies from two groups of post-menopausal women, a "Continuously treated group"
      (N = 16) receiving alendronate for ~ 10 years and a "Discontinued group" (N =
      15), alendronate treated for 5 years taking no antiresorptive medication during
      the following 5 years. Iliac crest bone biopsies were provided at 10 years.
      RESULTS: Key FTIRI parameters, mineral-to-matrix ratio, carbonate-to-phosphate
      ratio, acid phosphate substitution, and collagen cross-link ratio as well as
      heterogeneity of these parameters were similar for Continuously treated and
      Discontinued groups in age-adjusted models. The Discontinued group had 2% greater
      cortical crystallinity (p = 0.01), 31% greater cortical acid phosphate
      heterogeneity (p = 0.02), and 24% lower trabecular crystallinity heterogeneity (p
      = 0.02). CONCLUSIONS: Discontinuation of alendronate for 5 years did not affect
      key FTIRI parameters, supporting the hypothesis that discontinuation would have
      little impact on bone composition. Modest differences were observed in three
      parameters that are not likely to affect bone mechanical properties. These
      preliminary data suggest that a 5-year BP holiday is not harmful to bone
      composition.

PMID- 29204961
TI  - Patterns of convexal subarachnoid haemorrhage: clinical, radiological and outcome
      differences between cerebral amyloid angiopathy and other causes.
AB  - BACKGROUND: Cerebral amyloid angiopathy (CAA) is a common aetiology of convexal
      subarachnoid haemorrhage (cSAH) but little is known about its specific
      characteristics in comparison with cSAH from other causes. In this study we
      compared patients with CAA vs. non-CAA-related cSAH. METHODS: Retrospective
      review of baseline and follow-up data of consecutive patients admitted with a
      symptomatic acute cSAH. RESULTS: Sixty-two patients were included (mean age 66.2
      +/- 14.1 years), of whom 31 with probable CAA. CAA patients presented more
      frequently with transient symptoms (83.9 vs. 19.3%; p < 0.001) usually without
      headache (19.0 vs. 58.1%; p = 0.002). In CAA, these were essentially positive
      sensory disturbance that met the criteria of transient focal neurological
      episodes (TFNE). CAA was more often associated with cortical superficial
      siderosis (cSS) (80.6 vs. 0%; p < 0.001) and lobar cerebral microbleeds (83.4 vs.
      9%; p < 0.001). During a mean of 22 months of follow-up, recurrent symptomatic
      cSAH occurred in 4/27 (12.9%) CAA patients and in 0/27 non-CAA patients. Among 40
      patients with MRI follow-up, cSAH recurrences were observed in 44% of CAA
      patients vs. 13.3% of other cases (p = 0.08) and extension of cSS was detected
      only in CAA (60%) (p < 0.001). Acute cSAH evolved to cSS in 96 and 73.3% of CAA
      and non-CAA patients, respectively (p = 0.06). CONCLUSIONS: CAA differs from
      other cSAH in having TFNE as a frequent clinical presentation, a high prevalence
      of cSS and an increased risk of recurrent subarachnoid bleeding. However,
      evolution from acute cSAH to focal cSS may not be specific to CAA.

PMID- 29204962
TI  - Adult leukoencephalopathies with prominent infratentorial involvement can be
      caused by Erdheim-Chester disease.
AB  - BACKGROUND: Leukoencephalopathies with prominent involvement of cerebellum and
      brainstem, henceforward called prominent infratentorial leukoencephalopathies
      (PILs), encompass a variety of inherited and acquired white matter diseases.
      Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely
      under-diagnosed as cause of adult PIL. METHODS: We reviewed the clinical and
      laboratory information of ten consecutive sporadic adult patients with PIL of
      unknown origin, who were investigated for ECD. RESULTS: There were seven males
      and three females; mean age at clinical onset was 49.6 years (range 38-59);
      cerebellar ataxia with or without other neurological symptoms was the only or the
      main clinical manifestation; diabetes insipidus was present in three individuals.
      Eight patients had white matter focal supratentorial abnormalities, in addition
      to the infratentorial white matter changes. Six out of eight patients had spinal
      cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients,
      whole-body FDG-PET revealed increased glucose uptake in the long bones of the
      legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism
      in one patient. In eight patients, ECD was confirmed by bone scintigraphy,
      pathological data, or both. Two ECD patients treated with vemurafenib showed a
      marked improvement of neurological symptoms and brain MRI abnormalities at 1 year
      follow-up. CONCLUSIONS: Symptoms of PIL can be the only clinical manifestation of
      ECD. Adult patients with PIL of unknown origin should undergo investigations
      aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The
      early diagnosis allows starting disease-modifying therapies of an otherwise life
      threatening disease.

PMID- 29204963
TI  - The BRAIN test: a keyboard-tapping test to assess disability and clinical
      features of multiple sclerosis.
AB  - BACKGROUND: The BRadykinesia Akinesia INcordination (BRAIN) test is an online
      keyboard-tapping test previously validated as a sensitive tool for detecting
      signs of Parkinson's disease. OBJECTIVES: To determine whether the BRAIN test can
      measure disability in MS and identify the presence of pyramidal or cerebellar
      dysfunction. METHODS: Kinesia scores (KS, number of key taps in 30 s), akinesia
      times (AT, mean dwell time on each key) and incoordination scores (IS, variance
      of travelling time between keys) were calculated in 39 MS patients. These were
      correlated against the Expanded Disability Status Scale (EDSS) scores, pyramidal
      and cerebellar functional system scores and 9-hole peg test scores. RESULTS: EDSS
      correlated with KS (r = - 0.594, p < 0.001), AT (r = 0.464, p = 0.003) and IS (r
      = 0.423, p = 0.007). 9-HPT scores strongly correlated with KS (r = 0.926, p <
      0.001). Pyramidal scores correlated with KS (r = - 0.517, p < 0.001). Cerebellar
      scores correlated with KS (r = - 0.665, p < 0.001), AT (r = 0.567, p < 0.001) and
      IS (r = 0.546, p = 0.007). Receiver operating characteristic curves demonstrate
      that KS can distinguish between the presence or absence of pyramidal and
      cerebellar dysfunction with area under curve 0.840 (p < 0.001) and 0.829 (p <
      0.001), respectively. CONCLUSIONS: The BRAIN test can remotely measure disability
      in MS. Specific scores differ according to the presence and severity of pyramidal
      or extrapyramidal dysfunction. It demonstrates huge potential in monitoring
      disease progression in clinical trials.

PMID- 29204964
TI  - A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of
      the treatment of vestibular paroxysmia with oxcarbazepine.
AB  - OBJECTIVE: Vestibular paroxysmia (VP) is characterized by short, often
      oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes
      provoked by turning the head. Despite the description of the disease almost 40
      years ago (first termed "disabling positional vertigo"), no controlled treatment
      trial has been published to date. The Vestparoxy trial was designed as a
      randomized, placebo-controlled, double-blind cross-over trial to examine the
      therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable
      VP. METHODS: Patients were recruited from August 2005 to December 2011 in the
      outpatient Dizziness Unit of the Department of Neurology of the Munich University
      Hospital, and randomized to receive OXA (first week: 300 mg once per day, second
      week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month),
      followed by placebo or vice versa with a 1-month wash-out period in between. The
      primary endpoint was the number of days with one or more attacks. Secondary
      endpoints were the number of attacks during the observed days, and the median
      (for each day) duration of attacks. All these endpoints were assessed using
      standardized diaries collected at the end of each treatment phase. RESULTS: Forty
      three patients were randomized, 18 patients provided usable data (2525 patient
      days) for at least one treatment phase and were included in the main (intention
      to-treat) analysis. The most common reasons for discontinuation documented were
      adverse events. The risk of experiencing a day with at least one attack was 0.41
      under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67
      (95% CI 0.47-0.95, p = 0.025). The number of attacks during the observed days
      ratio was 0.53 (95% CI 0.42-0.68, p < 0.001) under OXA compared to placebo.
      Median attack duration was 4 s (Q25: 2 s, Q75: 120 s) under OXA, and 3 s (Q25: 2
      s, Q75: 60 s) under placebo treatment. When days with no attacks, i.e., duration
      = 0, were included in the analysis, these figures changed to 0 (Q25: 0, Q75: 3
      s), and 2 (Q25: 0, Q75: 6 s). No serious adverse events or new safety findings
      were identified during the trial. CONCLUSIONS: The Vestparoxy trial showed a
      significant reduction of VP attacks under OXA compared to placebo treatment,
      confirming the known and revealing no new side effects.

PMID- 29204965
TI  - Assessing biodegradation of furfuryl alcohol using Pseudomonas putida MTCC 1194
      and Pseudomonas aeruginosa MTCC 1034 and its kinetics.
AB  - The biodegradation of furfuryl alcohol (FA) in shake flask experiments using a
      pure culture of Pseudomonas putida (MTCC 1194) and Pseudomonas aeruginosa (MTCC
      1034) was studied at 30  degrees C and pH 7.0. Experiments were performed at
      different FA concentrations ranging from 50 to 500 mg/l. Before carrying out the
      biodegradation studies, the bacterial strains were acclimatized to the
      concentration of 500 mg/l of FA by gradually raising 100 mg/l of FA in each step.
      The well acclimatized culture of P. putida and P. aeruginosa degraded about 80
      and 66% of 50 mg/l FA, respectively. At higher concentration of FA, the
      percentage of FA degradation decreased. The purpose of this study was to
      determine the kinetics of biodegradation of FA by measuring biomass growth rates
      and concentration of FA as a function of time. Substrate inhibition was
      calculated from experimental growth parameters using the Haldane equation. Data
      for P. putida were determined as u max  = 0.23 h-1, K s  = 23.93 mg/l and K i  =
      217.1 mg/l and for P. aeruginosa were determined as u max  = 0.13 h-1, K s  =
      21.3 mg/l and K i  = 284.9 mg/l. The experimental data were fitted in Haldane,
      Aiba and Edwards inhibition models.

PMID- 29204967
TI  - The importance of a well-structured pancreatic screening program for familial and
      hereditary pancreatic cancer.

PMID- 29204966
TI  - Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in
      Regulating the Pathophysiological Actions of Prostaglandins.
AB  - Solute carrier organic anion transporter family member 2A1 (OATP2A1, encoded by
      the SLCO2A1 gene), which was initially identified as prostaglandin transporter
      (PGT), is expressed ubiquitously in tissues and mediates the distribution of
      prostanoids, such as PGE2, PGF2alpha, PGD2 and TxB2. It is well known to play a
      key role in the metabolic clearance of prostaglandins, which are taken up into
      the cell by OATP2A1 and then oxidatively inactivated by 15-ketoprostaglandin
      dehydrogenase (encoded by HPGD); indeed, OATP2A1-mediated uptake is the rate
      limiting step of PGE2 catabolism. Consequently, since OATP2A1 activity is
      required for termination of prostaglandin signaling via prostanoid receptors, its
      inhibition can enhance such signaling. On the other hand, OATP2A1 can also
      function as an organic anion exchanger, mediating efflux of prostaglandins in
      exchange for import of anions such as lactate, and in this context, it plays a
      role in the release of newly synthesized prostaglandins from cells. These
      different functions likely operate in different compartments within the cell.
      OATP2A1 is reported to function at cytoplasmic vesicle/organelle membranes. As a
      regulator of the levels of physiologically active prostaglandins, OATP2A1 is
      implicated in diverse physiological and pathophysiological processes in many
      organs. Recently, whole exome analysis has revealed that recessive mutations in
      SLCO2A1 cause refractory diseases in humans, including primary hypertrophic
      osteoarthropathy (PHO) and chronic non-specific ulcers in small intestine (CNSU).
      Here, we review and summarize recent information on the molecular functions of
      OATP2A1 and on its physiological and pathological significance.

PMID- 29204968
TI  - Advantages to Using Social-Behavioral Models of Medication Adherence in Research
      and Practice.
AB  - Achieving and sustaining high levels of adherence to medication regimens is
      essential to improving health outcomes, but continues to be a challenge for a
      sizable proportion of patients. Decades of research suggests that medication
      adherence is determined by a complex constellation of factors. Social-behavioral
      science research has focused on creating frameworks that identify which
      contextual, personal, social, or drug-related factors appear to most influence
      adherence. Comprehensive models of adherence propose specific structural
      relationships between these factors that can be used to plan for, implement, and
      monitor programs that seek to optimize adherence. The use of social-behavioral
      models offers multiple advantages in both practice and research environments;
      however, the breadth and depth of these models can deter many from engaging in
      this important exercise. To promote the use of social-behavioral frameworks and
      models of adherence, we provide a brief overview of the advantages in using a
      social-behavioral lens in adherence work, a sampling of models used in HIV
      medication adherence research that have high generalizability to other
      conditions, and practical guidance for grounding adherence promotion strategies
      in evidence informed by social-behavioral science research.

PMID- 29204970
TI  - Taking an Interdisciplinary Approach to Understanding and Improving Medication
      Adherence.

PMID- 29204969
TI  - Advancing the Science and Practice of Medication Adherence.
AB  - Medication adherence remains a significant unmet challenge for optimizing patient
      outcomes. Recent advances in the conceptualization, measurement, and support of
      medication adherence offer fresh opportunities to make a meaningful impact on
      adherence-related behavior and outcomes. These advances emphasize the
      multifaceted and dynamic nature of medication adherence, provide novel methods
      for monitoring medication adherence in clinical care, and articulate a set of
      multilevel strategies to more effectively improve and sustain medication
      adherence. Here, we offer recommendations for how clinicians can better engage
      with, and benefit from, these innovations to improve patient medication adherence
      and associated treatment outcomes.

PMID- 29204971
TI  - Cultural Issues in Medication Adherence: Disparities and Directions.
AB  - Adherence to medications is dependent upon a variety of factors, including
      individual characteristics of the patient, the patient's family and culture,
      interactions with healthcare providers, and the healthcare system itself. Because
      of its association with worse outcomes, poor medication adherence is considered a
      potential contributor to disparities in health outcomes observed for various
      conditions across racial and ethnic groups. While there are no simple answers, it
      is clear that patient, provider, cultural, historical, and healthcare system
      factors all play a role in patterns of medication use. Here, we provide an
      overview of the interface between culture and medication adherence for chronic
      conditions; discuss medication adherence in the context of observed health
      disparities; provide examples of cultural issues in medication adherence at the
      individual, family, and healthcare system/provider level; review potential
      interventions to address cultural issues in medication use; and provide
      recommendations for future work.

PMID- 29204972
TI  - Interprofessional Collaboration: A Qualitative Study of Non-Physician
      Perspectives on Resident Competency.
AB  - BACKGROUND: The Association of American Medical Colleges (AAMC) includes the
      ability to collaborate in an interprofessional team as a core professional
      activity that trainees should be able to complete on day 1 of residency (Med Sci
      Educ. 26:797-800, 2016). The training that medical students require in order to
      achieve this competency, however, is not well established (Med Sci Educ. 26:457
      61, 2016), and few studies have examined non-physician healthcare professionals'
      perspectives regarding resident physicians' interprofessional skills. OBJECTIVE:
      This study aims to describe non-physicians' views on barriers to collaboration
      with physicians, as well as factors that contribute to good collaborative
      relationships. PARTICIPANTS: Nurses, social workers, case managers, dietitians,
      rehabilitation therapists, and pharmacists at one academic medical center,
      largely working in the inpatient setting. APPROACH: A qualitative study design
      was employed. Data were collected from individual interviews and focus groups
      comprising non-physician healthcare professionals. KEY RESULTS: Knowledge gaps
      identified as impeding interprofessional collaboration included inadequate
      understanding of current roles, potential roles, and processes for non-physician
      healthcare professionals. Specific physician behaviors that were identified as
      contributing to good collaborative relationships included mutual support such as
      backing up other team members and prioritizing multidisciplinary rounds, and
      communication including keeping team members informed, asking for their input,
      physicians explaining their rationale, and practicing joint problem-solving with
      non-physicians. CONCLUSIONS: Discussion of how physician trainees can best learn
      to collaborate as members of an interprofessional team must include non-physician
      perspectives. Training designed to provide medical students and residents with a
      better understanding of non-physician roles and to enhance mutual support and
      communication skills may be critical in achieving the AAMC's goals of making
      physicians effective members of interprofessional teams, and thus improving
      patient-centered care. We hope that medical educators will include these areas
      identified as important by non-physicians in targeted team training for their
      learners.

PMID- 29204973
TI  - External Validation of a Tool Predicting 7-Year Risk of Developing Cardiovascular
      Disease, Type 2 Diabetes or Chronic Kidney Disease.
AB  - BACKGROUND: Chronic cardiometabolic diseases, including cardiovascular disease
      (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many
      modifiable risk factors and can be prevented using combined prevention programs.
      Valid risk prediction tools are needed to accurately identify individuals at
      risk. OBJECTIVE: We aimed to validate a previously developed non-invasive risk
      prediction tool for predicting the combined 7-year-risk for chronic
      cardiometabolic diseases. DESIGN: The previously developed tool is stratified for
      sex and contains the predictors age, BMI, waist circumference, use of
      antihypertensives, smoking, family history of myocardial infarction/stroke, and
      family history of diabetes. This tool was externally validated, evaluating model
      performance using area under the receiver operating characteristic curve (AUC)
      assessing discrimination-and Hosmer-Lemeshow goodness-of-fit (HL) statistics
      assessing calibration. The intercept was recalibrated to improve calibration
      performance. PARTICIPANTS: The risk prediction tool was validated in 3544
      participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).
      KEY RESULTS: Discrimination was acceptable, with an AUC of 0.78 (95% CI 0.75
      0.81) in men and 0.78 (95% CI 0.74-0.81) in women. Calibration was poor (HL
      statistic: p < 0.001), but improved considerably after intercept recalibration.
      Examination of individual outcomes showed that in men, AUC was highest for CKD
      (0.85 [95% CI 0.78-0.91]) and lowest for T2D (0.69 [95% CI 0.65-0.74]). In women,
      AUC was highest for CVD (0.88 [95% CI 0.83-0.94)]) and lowest for T2D (0.71 [95%
      CI 0.66-0.75]). CONCLUSIONS: Validation of our previously developed tool showed
      robust discriminative performance across populations. Model recalibration is
      recommended to account for different disease rates. Our risk prediction tool can
      be useful in large-scale prevention programs for identifying those in need of
      further risk profiling because of their increased risk for chronic
      cardiometabolic diseases.

PMID- 29204974
TI  - Effects of Discontinuation of Urate-Lowering Therapy: A Systematic Review.
AB  - BACKGROUND: Urate-lowering therapy (ULT) is associated with low rates of
      adherence, leading to a potential risk of relapse of gouty arthritis, tophi, or
      urolithiasis. Our main aim was to identify the recurrence of gouty arthritis,
      tophi, or urolithiasis after discontinuation of ULT. Secondary aims included an
      assessment of ULT reintroduction rates and factors associated with relapse.
      METHODS: We conducted a systematic literature review of clinical studies
      investigating the effect of discontinuing any ULT (allopurinol, febuxostat,
      probenecid, sulfinpyrazone, benzbromarone) in adults on long-term therapy. We
      searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE,
      Science Citation Index, and ClinicalTrials.gov from inception to March 2016.
      Conference abstracts of the ACR/ARHP and EULAR annual conferences were hand
      searched. Study quality was assessed using the first eight items of the
      methodological index for non-randomized studies (MINORS) tool. The review
      protocol is registered with PROSPERO (CRD42016042048). RESULTS: A total of 4640
      articles were identified, eight of which were ultimately included. Most of these
      studies predated 2000. MINORS scores ranged from 5 to 10 out of a possible 16.
      Mean follow-up duration after discontinuation ranged from 12 to 96 months. Five
      studies focused on discontinuation of ULT in gouty arthritis and tophi, two in
      urolithiasis, and one in asymptomatic hyperuricemia. Relapse rates were high in
      gout (36-81%) and lower in urolithiasis (15%). Relapses occurred 1-4.5 years
      after ULT discontinuation. In one study, a low serum urate level before and after
      ULT discontinuation was associated with lower gout recurrence. DISCUSSION:
      Relapse of gout is common although delayed after discontinuation of ULT. Short
      term prognosis after ULT discontinuation appears favorable if the serum urate
      level was low before ULT discontinuation. The results of this review are limited
      by the paucity of existing studies and their low quality. Further comparative
      studies should consider larger primary care populations and discontinuation of
      febuxostat.

PMID- 29204975
TI  - Characteristics and Disparities among Primary Care Practices in the United
      States.
AB  - BACKGROUND: Despite new incentives for US primary care, concerns abound that
      patient-centered practice capabilities are lagging. OBJECTIVE: Describe the
      practice structure, patient-centered capabilities, and payment relationships of
      US primary care practices; identify disparities in practice capabilities. DESIGN:
      Analysis of the 2015 Medical Organizations Survey (MOS), part of the nationally
      representative Medical Expenditure Panel Survey (MEPS). SETTING: Practice
      reported information from primary care practices of MEPS respondents who reported
      receiving primary care and made at least one visit in 2015 to that practice.
      PARTICIPANTS: Surveyed primary care practices (n = 4318; 77% response rate)
      providing primary care to 7161 individuals, representing 101,159,263 Americans.
      MAIN MEASURES: Practice structure (ownership and personnel); practice
      capabilities (certification as a patient-centered medical home [PCMH], electronic
      health record [EHR] use, and x-ray capability); and payment orientation
      (accountable care organization [ACO] and capitation). KEY RESULTS: Independently
      owned practices served 55% of patients, hospital-owned practices served 19%, and
      nonprofit/government/academic-owned served 20%. Solo practices served 25% of
      patients and practices with 2-10 physicians served 53% of patients. Forty-one
      percent of patients were served by practices certified as PCMHs. Practices with
      EHRs cared for 90% of patients and could exchange secure messages with 78% of
      patients. Practices with in-office x-ray capability cared for 34% of patients.
      Practices participating in ACOs and capitation served 44% and 46% of patients,
      respectively. Primary care patients in the South, compared to the rest of the
      country, had less access to nearly all practice capabilities, including patient
      care coordination (adjusted difference, 13% [95% CI, 8-18]) and secure EHR
      messaging (adjusted difference, 6% [95% CI, 1-10]). Uninsured patients were less
      likely to be served at a practice that used an EHR (adjusted difference, 9% [95%
      CI, 2-16]). CONCLUSIONS: Participants' primary care practices were mostly
      independently owned, nearly always used EHRs (albeit of varying capability), and
      frequently participated in innovative payment arrangements for a portion of their
      patients. Patient practices in the South had fewer capabilities than the rest of
      the country.

PMID- 29204976
TI  - Three Year Functional Trajectories Among Old Age Survivors and Decedents: Dying
      Eliminates a Racial Disparity.
AB  - BACKGROUND: Long-term trajectories of disability comparing decedents and
      survivors and differences by race have not been assessed. OBJECTIVE: To examine
      self-reported difficulty in walking a quarter mile and the need for assistance
      with activities of daily living (ADL) beginning 3 years before death among
      decedents and age- and gender-matched survivors. DESIGN: A case-control sample
      drawn from the Health, Aging and Body Composition Study (Health ABC). Data were
      collected between 1997 and 2015. PARTICIPANTS: Of the 1991 participants who died
      by the end of the study, 1410 were interviewed for 3 years prior to death,
      including an interview 6 months before dying. Of these, 1379 decedents were
      successfully matched by age and gender with 1379 survivors and tracked over the
      same 3-year period. MAIN MEASURES: Self-reported difficulty walking a quarter
      mile and the ability to perform activities of daily living without assistance
      (bathing, dressing, transferring). KEY RESULTS: Decedents (mean age at death, 84)
      increased in mobility disability from 44.1% 3 years before death to 69.4% 6
      months before death and in ADL disability from 32.9% to 58.4%. Among survivors,
      mobility disability increased from 31.4% to 40.7% and ADL disability from 17.4%
      to 31.4%. The proportion of decedents and survivors with mobility disability
      differed significantly in adjusted models at all assessment points (p < 0.0001).
      African-American survivors were significantly more disabled than White survivors
      at all points (p < 0.0001), but trajectories of disability among decedents did
      not differ by race in the last 18 months of life (p = 0.35). CONCLUSIONS:
      Trajectories of self-reported disability differ between survivors and decedents.
      Older adults who died were more disabled 3 years before death and also had a
      greater risk of increasing disability over each subsequent 6-month assessment.
      The gap in disability between African Americans and Whites was erased in the
      final 1 to 1.5 years before death.

PMID- 29204977
TI  - Managing Concerning Behaviors in Patients Prescribed Opioids for Chronic Pain: A
      Delphi Study.
AB  - BACKGROUND: Current guideline-recommended monitoring of patients prescribed long
      term opioid therapy (LTOT) for chronic pain will likely result in increased
      identification of behaviors of concern for misuse and addiction, but there is a
      dearth of empiric evidence about how these behaviors should be managed.
      OBJECTIVE: To establish expert consensus about treatment approaches for common
      and challenging concerning behaviors that arise among patients on LTOT. DESIGN:
      We used a Delphi approach, which allows for generation of consensus.
      PARTICIPANTS: Participants were clinical experts in chronic pain and opioid
      prescribing recruited from professional societies and other expert groups. MAIN
      MEASURES: The Delphi process was conducted online, and consisted of an initial
      brainstorming round to identify common and challenging behaviors, a second round
      to identify management strategies for each behavior, and two rounds to establish
      consensus and explore disagreement/uncertainty. KEY RESULTS: Forty-two
      participants completed round 1, 22 completed round 2, 30 completed round 3, and
      28 completed round 4. Half of round 1 participants were female (52%), and the
      majority were white (83%). Most (71%) were physicians, and most participants
      practiced in academic primary (40%) or specialty care (19%).The most frequently
      cited common and challenging behaviors were missing appointments, taking opioids
      for symptoms other than pain, using more opioid medication than prescribed,
      asking for an increase in opioid dose, aggressive behavior, and alcohol and other
      substance use. Across behaviors, participants agreed that patient education and
      information gathering were important approaches. Participants also agreed that
      stopping opioids is not important initially, but if initial approaches do not
      work, tapering opioids and stopping opioids immediately may become important
      approaches. CONCLUSIONS: This study presents clinical expert consensus on how to
      manage concerning behaviors among patients on LTOT. Future research is needed to
      investigate how implementing these management strategies would impact patient
      outcomes, practice and policy.

PMID- 29204979
TI  - Treatment of Spontaneous Subarachnoid Hemorrhage and Self-Reported
      Neuropsychological Performance at 6 Months - Results of a Prospective Clinical
      Pilot Study on Good-Grade Patients.
AB  - AIM: Limited focus has been placed on neuropsychological patient profiles after
      spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled
      study in good-grade sSAH patients to evaluate the time course of treatment
      specific differences in cognitive processing after sSAH. MATERIAL AND METHODS:
      Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients
      received endovascular aneurysm occlusion (EV), 6 patients were treated
      microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent
      standardized intensive medical care. No patient experienced serious vasospasm
      related ischemic or hemorrhagic complications. All patients were subjected to
      neuropsychological self-report assessment (36-Item Short Form Health Survey and
      ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of
      bleeding (t1) and at the 6-month follow-up (FU; t < sub > 2 < /sub > ). RESULTS:
      From t1 to t < sub > 2 < /sub > , MS and EV patients significantly improved in
      physical functioning (Pfi; p=.001 each) and the physical component summary
      (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions
      (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened.
      At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain
      (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of
      test differences showed a significant alleviation in nutrition disorder in MS
      (vs. EV p=.009). CONCLUSION: All sSAH groups reported a significant deterioration
      in health. Though both MS and EV patients, improved in several physical items
      over time, our data suggest a better short-term Pfi, less Pain and improved
      nutrition disorder in surgically treated patients. pSAH patients performed
      significantly better in various aspects of physical and psychological functioning
      than patients with aneurysmal SAH.

PMID- 29204978
TI  - Role of Glypican-3 in the growth, migration and invasion of primary hepatocytes
      isolated from patients with hepatocellular carcinoma.
AB  - BACKGROUND: Recently, Glypican-3 (GPC3) has been identified as a potential
      hepatocellular carcinoma (HCC) diagnostic and/or therapeutic target. GPC3 has
      been found to be up-regulated in HCC and to be absent in normal and cirrhotic
      liver. As yet, however, the molecular characteristics of GPC3 and its role in HCC
      cell physiology and development are still undefined. METHODS: Human hepatocyte
      cultures were established from 10 HCC patients. Additional liver samples were
      obtained from 5 patients without cirrhosis and/or HCC. Soft agar colony
      formation, (co-)immunofluorescence and Western blot assays were used to
      characterize the hapatocyte cultures. The expression of GPC3 in the hepatocytes
      was silenced using siRNA, after which, apoptosis, scratch wound migration and
      transwell invasion assays were performed. RESULTS: We found that in HCC precursor
      hepatocytes GPC3 is increasingly expressed in different forms and at different
      locations, i.e., a non-cleaved form (70 kDa) was found to be localized in the
      cytoplasm while a N-terminal cleaved form (N-GPC3: 40 kDa) was fond to be
      localized in the cytoplasm and at the extracellular side of hepatocyte membranes.
      In addition, we found that the non-cleaved form of GPC3 co-localizes with Furin
      Convertase in the Golgi apparatus. We also found that, similar to GPC3, Furin
      Convertase is expressed in HCC precursor cells, suggesting a role in GPC3
      processing. Subsequent siRNA-mediated GPC3 silencing resulted in a temporary
      inhibition of cell proliferation, migration and ivasion, while inducing apoptosis
      in transformed hepatocytes. CONCLUSION: Our data reveal new aspects of the role
      of GPC3 in early hepatocyte transformation. In addition we conclude that GPC3 may
      serve as a new HCC immune-therapeutic target.

PMID- 29204980
TI  - Usefulness and Radiological Evaluation of Accuracy of the Innovative "Smart" Hand
      Technique for Pedicle Screw Placement: An Anatomical Study.
AB  - AIM: To use a smartphone application (app) during pedicle screw placement
      navigation and examine the accuracy of this application on an anatomical dry
      vertebrae model. MATERIAL AND METHODS: Seventy-six dry vertebrae were used for
      this study, and pedicle entry points and projections of pedicle screw trajectory
      lines in the lateral and superior aspects of the vertebral body were identified
      and drawn for each vertebra bilaterally. In each position, all angulations were
      measured directly before the procedure manually. One hundred and fifty two
      pedicle screws were inserted as a simulation of screw placement with the guidance
      of the angle-meter smart app. Accuracy of the method was tested according to the
      occurrence of bone penetration while the angular deviation of the inserted screws
      was evaluated in computed tomography images. RESULTS: The mean deviation for 76
      pedicle screws on the right side was 2.30 degrees +/-1.78 degrees  in the
      horizontal plane and 2.17 degrees +/-1.57 degrees  in the sagittal plane; and on
      the left side, 3.01 degrees +/-1.83 degrees  in the horizontal plane and 2.38
      degrees +/-1.68 degrees  in the sagittal plane. No bone penetration occurred
      during 152 pedicle screw placements. According to the t-test results, there were
      significant differences between the two groups in the craniocaudal direction of
      the right side pedicle screws and in the craniocaudal direction of left sided
      pedicle screws. CONCLUSION: The free smartphone app presented here as an angle
      meter is a safe digital device for spinal instrumentation procedures. As a
      prototype of future pedicle screw fixation systems, it should be improved in
      terms of its feasibility and compatibility with screw probes. This may lead to a
      useful mobile digital angle-meter for spinal procedures.

PMID- 29204981
TI  - Neuroprotective Effects of Oleocanthal, a Compound in Virgin Olive Oil, in a Rat
      Model of Traumatic Brain Injury.
AB  - AIM: To evaluate the neuroprotective effects of deocanthal OC in a rat model of
      traumatic brain injury (TBI). MATERIAL AND METHODS: Twenty-six adult male, Wistar
      albino rats were used. The rats were divided into 4 groups. Group 1 was the sham
      group (n=5). Group 2 was the trauma group (n=5) where rats were treated with 10
      mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were
      treated with 10 (group 3, n=8) or 30 (group 4, n=8) mg/kg OC IP twice a day. For
      each group, brain samples were collected 72 hours after injury. Brain samples and
      blood were evaluated with histopathological and biochemical methods. RESULTS:
      Histopathological evaluation revealed a significant difference between Group 2
      and Group 4. Biochemical findings demonstrated that the oxidative stress index
      was highest in Group 2 and lowest in Group 4. CONCLUSION: OC has a protective
      effect on neural cells after TBI. This effect is achieved by reducing oxidative
      stress and apoptosis.

PMID- 29204982
TI  - Assessment of the MRI and Behavioral Test Results in Focal Cerebral Ischemia
      Reperfusion Model in Rat after Separate and Combined Use of Mouse-Derived Neural
      Progenitor Cells, Human-Derived Neural Progenitor Cells and Atorvastatin.
AB  - AIM: We aimed 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: 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 rate compared with control group. hNPC group had
      significantly better performance and lower infarct area rate than mNPC group.
      Addition of atorvastatin to stem cell therapy significantly improved functional
      outcome, despite it didn't affect the infarct area rate on MRI. Anti-inflammatory
      response in the infarcted area was higher in mNPC group. NPC transplantation
      significantly reduced the amount of microglia while they caused significant
      increase in the amount of astrocytes. CD8a+ T lymphocyte and granzyme B
      activities were not detected in none of the subjects. CONCLUSION: Both hNPC and
      mNPC treatments significantly improved functional outcome, and reduced infarct
      area rate after stroke. Atorvastatin enhanced the therapeutic potency of NPCs,
      including neurological improvement.

PMID- 29204983
TI  - Phyllanthus emblica Linn. fruit extract potentiates the anticancer efficacy of
      mitomycin C and cisplatin and reduces their genotoxicity to normal cells in
      vitro.
AB  - OBJECTIVE: Fruit of Phyllanthus emblica Linn. (PE) is widely consumed as a
      functional food and used as a folk medicine due to its remarkable nutritional and
      pharmacological effects. Mitomycin C (MMC) and cisplatin (cDDP) are the most
      widely used forms of chemotherapeutic drug, but their clinical use is limited by
      their genotoxicity to normal cells. We aimed to determine whether PE has
      potential to reduce the genotoxicity, while improving the anticancer effect, of
      MMC and cDDP. METHODS: Cell proliferation was evaluated using the trypan blue
      exclusion assay and colony-forming assay. Genomic instability (GIN) was measured
      using the cytokinesis-block micronucleus assay. RESULTS: Co-treatment (72 h) with
      PE at 20-320 MUg/ml significantly enhanced the efficacy of MMC (0.05 MUg/ml) and
      cDDP (1 MUg/ml) against Colo205 colorectal cancer cells (P<0.05), and at 80-320
      MUg/ml significantly decreased MMC- and cDDP-induced GIN and multinucleation in
      normal colonic NCM460 cells (P<0.05). PE significantly decreased the mitotic
      index (P<0.01), blocked mitotic progression (P<0.05), and promoted apoptosis
      (P<0.01) in MMC- and cDDP-treated NCM460 cells, suggesting that PE-mediated
      inhibition of mitosis and induction of apoptosis may limit the division and
      survival of highly damaged cells. Also, PE was found to inhibit the clonal
      expansion of MMC- and cDDP-treated NCM460 cells (P<0.05) and decrease the
      heterogeneity of the surviving clones. CONCLUSIONS: PE potentiates the anticancer
      efficacy of MMC and cDDP, while preventing their genotoxicity and inhibiting
      clonal expansions of unstable genomes in normal cells. These data suggest that PE
      has the potential to reduce the risk of secondary cancers induced by
      chemotherapeutics.

PMID- 29204984
TI  - Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating
      intracellular trafficking of lung resistance-related protein.
AB  - Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The
      expression of lung resistance-related protein (LRP), a non-ATP-binding cassette
      (ABC) transporter, is high in tumor cells, resulting in their resistance to a
      variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance
      is not yet explicit. Our previous studies had shown that Kinesin KIF4A was
      overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells
      (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or
      A549/DDP cells significantly affects cisplatin resistance but the detailed
      mechanisms remain unclear. Here, we performed co-immunoprecipitation experiments
      to show that the tail domain of KIF4A interacted with the N-terminal of LRP.
      Immunofluorescence images showed that both the ability of binding to LRP and the
      motility of KIF4A were essential for the dispersed cytoplasm distribution of LRP.
      Altogether, our results shed light on a potential mechanism in that motor protein
      KIF4A promotes drug resistance of lung adenocarcinoma cells through transporting
      LRP-based vaults along microtubules towards the cell membrane. Thus KIF4A might
      be a cisplatin resistance-associated protein and serves as a potential target for
      chemotherapeutic drug resistance in lung cancer.

PMID- 29204985
TI  - Comparison of the characteristics of macrophages derived from murine spleen,
      peritoneal cavity, and bone marrow.
AB  - Macrophages have a diverse set of functions based upon their activation states.
      The activation states, including resting (M0) and polarizing (M1 and M2) states,
      of macrophages derived from the mouse bone marrow, spleen, and peritoneal cavity
      (BMs, SPMs, and PCMs, respectively) were compared. We evaluated the macrophage
      yield per mouse and compared the surface markers major histocompatibility complex
      (MHC) II and CD86 by flow cytometry. The relative mRNA levels of tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-1beta, mannose receptor (MR), and Ym1
      in the M0, M1, and M2 states were also compared using real-time polymerase chain
      reaction (PCR) analysis. Bone marrow yielded the most macrophages with the best
      homogeneity, but they were polarized toward the M2 phenotype. All three types of
      macrophages had the capacity to polarize into the M1 and M2 states, but SPMs had
      a stronger capacity to polarize into M1. The three types of macrophages showed no
      differences in their capacity to polarize into the M2 state. Therefore, the three
      types of macrophages have distinct characteristics regardless of their resting or
      polarizing states. Although bone marrow can get large amounts of homogeneous
      macrophages, the macrophages cannot replace tissue-derived macrophages.

PMID- 29204986
TI  - Polymorphisms of the IGF1 gene and their association with growth traits, serum
      concentration and expression rate of IGF1 and IGF1R in buffalo.
AB  - The insulin-like growth factor 1 (IGF1) gene is a member of the group of
      somatotropin axis genes that play a significant role in cell proliferation and
      growth of muscles. Here, we searched for polymorphisms in buffalo IGF1 and found
      two novel single nucleotide polymorphisms (SNPs), G64A and G280A, in the
      noncoding sequences of exon 1 and exon 4, respectively. Statistical analysis of
      different genotypes showed that the individuals with GG genotypes had
      significantly (P<0.05) higher body weight (BW) and average daily gain (ADG) than
      those with other genotypes at ages of 3-6 months in G64A SNP and 6-9 months in
      G280A SNP. The combined genotypes of these two SNPs produced three haplotypes,
      GG/GG, AG/AG, and AA/AA, which were significantly associated (P<0.0001) with BW
      and ADG at an age from 3 to 12 months. Buffaloes with the homozygous GG/GG
      haplotype showed higher growth performance than other buffaloes. The two SNPs
      were correlated with mRNA levels of IGF1 and IGF1 receptor (IGF1R) in
      semitendinosus muscle as well as with the serum concentration level of IGF1.
      Also, buffaloes with GG/GG haplotype showed higher mRNA and serum concentration
      levels. The data revealed that these two SNPs could be valuable genetic markers
      for selection of Egyptian buffaloes for better performance in the population.

PMID- 29204987
TI  - Monoclonal antibody-based serological assays for detection of Potato virus S in
      potato plants.
AB  - Potato virus S (PVS) often causes significant losses in potato production in
      potato-growing countries. In this study, the ordinary strain of PVS (PVSO) was
      purified from PVS-infected potato plants and used as the immunogen to produce
      hybridomas secreting monoclonal antibodies (MAbs). Five highly specific and
      sensitive murine MAbs (1A3, 16C10, 18A9, 20B12, and 22H4) against PVS were
      prepared using conventional hybridoma technology. Using these MAbs, tissue print
      enzyme-linked immunosorbent assay (ELISA), dot-ELISA, and double-antibody
      sandwich (DAS)-ELISA were developed for sensitive and specific detection of PVS
      infection in potato plants. The results of sensitivity assays revealed that PVS
      could be reliably detected in PVS-infected leaf crude extracts diluted at 1:10
      240 and 1:163 840 (w/v, g/ml) in phosphate buffer saline (PBS) by dot-ELISA and
      DAS-ELISA, respectively. Twenty-two samples collected from potato fields in
      Yunnan Province, China were tested for PVS infection using the serological assays
      we had developed, and 14 of them were found to be positive. This indicates that
      PVS is now prevalent in potato fields in Yunnan Province.

PMID- 29204988
TI  - Effects of dietary fresh fermented soybean meal on growth performance, ammonia
      and particulate matter emissions, and nitrogen excretion in nursery piglets.
AB  - This study was conducted to investigate the effects of fresh fermented soybean
      meal (FSM) on the growth performance of nursery piglets, nitrogen excretion in
      feces, and the concentrations of ammonia (NH3) and particulate matter (PM) in the
      piggery. A total of 472 nursery piglets (Landrace*Yorkshire, (16.3+/-0.36) kg
      body weight) were randomly allocated into two treatments with 236 pigs in each
      treatment. The pigs were fed the basal diet without fresh FSM (control) or diet
      containing 10% (100 g/kg) fresh FSM (FSM group), and the crude protein content of
      the two groups was consistent. The feeding trial lasted for 28 d. The results
      showed that the pigs fed fresh FSM had increased (P<0.05) average daily gain
      (ADG) compared with the control. There was no significant difference (P>0.05) in
      feed to gain ratio (F:G) between the two groups. During the whole experiment, the
      concentration of NH3 in the piggery decreased (P<0.05) by 19.0%, and the
      concentrations of PM (PM10 and PM2.5) in the piggery decreased (P<0.05) by 19.9%
      and 11.6%, respectively, in the FSM group, compared with the control. The ammonia
      nitrogen and nitrite content in feces increased (P<0.05) by 32.9% and 28.4%,
      respectively, in the FSM group. The fecal pH declined (P<0.05) significantly in
      the FSM group compared with the control. At the end of experiment, total protein
      (TP) concentration was increased (P<0.05) significantly and blood urea nitrogen
      (BUN) concentration was decreased (P<0.05) for pigs fed the diet with fresh FSM.
      The results indicated that dietary fresh FSM not only improved the growth
      performance of nursery piglets, but also reduced the NH3 concentration in the
      piggery due to nitrogen conversion, and decreased the concentrations of PM10 and
      PM2.5 in the piggery.

PMID- 29204989
TI  - Effects of glucose and gibberellic acid on glucosinolate content and antioxidant
      properties of Chinese kale sprouts.
AB  - Glucosinolates, anthocyanins, total phenols, and vitamin C, as well as
      antioxidant capacity, were investigated in Chinese kale sprouts treated with both
      glucose and gibberellic acid (GA3). The combination of 3% (0.03 g/ml) glucose and
      5 MUmol/L GA3 treatment was effective in increasing glucosinolate content while
      glucose or GA3 treatment alone did not influence significantly almost all
      individual glucosinolates or total glucosinolates. The total phenolic content and
      antioxidant activity of Chinese kale sprouts were enhanced by combined treatment
      with glucose and GA3, which could be useful in improving the main health
      promoting compounds and antioxidant activity in Chinese kale sprouts.

PMID- 29204991
TI  - Efficacy of amiodarone and lidocaine for preventing ventricular fibrillation
      after aortic cross-clamp release in open heart surgery: a meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: The relative preventative efficacy of amiodarone and lidocaine for
      ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during
      open heart surgery has not been determined. This meta-analysis was designed to
      systematically evaluate the influence of amiodarone, lidocaine, or placebo on the
      incidence of VF after ACC. METHODS: Prospective randomized controlled trials
      (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or
      amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the
      Cochrane Library were searched for relevant RCTs. Fixed or randomized effect
      models were applied according to the heterogeneity of the data from the selected
      studies. RESULTS: We included eight RCTs in the analysis. Pooled results
      suggested that the preventative effects of amiodarone and lidocaine were
      comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80,
      P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51
      to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The
      percentage of patients requiring electric defibrillation counter shocks (DCSs)
      did not differ significantly among patients administered amiodarone (RR=0.21, 95%
      CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or
      the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16). CONCLUSIONS: Amiodarone and
      lidocaine are comparably effective in preventing VF after ACC, but the percentage
      of patients who subsequently require DCSs does not differ among those
      administered amiodarone, lidocaine, or placebo.

PMID- 29204992
TI  - Latest Developments in the Management of AMD.

PMID- 29204993
TI  - Update on the Use of Anti-VEGF Intravitreal Therapies for Retinal Vein
      Occlusions.
AB  - The use of anti-vascular endothelial growth factor (VEGF) therapy in
      ophthalmology has profoundly changed our management and treatment of conditions
      such as cystoid macular edema, diabetic macular edema, choroidal
      neovascularization, and other proliferative retinopathies. Although initially
      used for the treatment of choroidal neovascularization in neovascular age-related
      macular degeneration, their application has spread rapidly for other indications
      as their outcomes have often outperformed previously existing treatments. Retinal
      vein occlusion (RVO) continues to be one of the leading causes of vision loss
      secondary to macular edema, in addition to macular ischemia and
      neovascularization in more severe cases. Before the availability of anti-VEGF
      therapy, the use of macular grid laser and panretinal photocoagulation was the
      mainstay of treatment of macular edema and neovascularization, respectively, in
      patients with RVOs. Two landmarks studies established the guidelines of these
      treatments for nearly a quarter century. Since the availability of anti-VEGF
      agents, there has been a paradigm shift in the treatment of RVO. Most
      importantly, there has also been a significant improvement in visual outcomes in
      these patients. The goal of this article is to provide a review of the pertinent
      clinical studies that have investigated the use of anti-VEGF in patients with
      retinal vein occlusions.

PMID- 29204990
TI  - Apoptosis induction of colorectal cancer cells HTL-9 in vitro by the transformed
      products of soybean isoflavones by Ganoderma lucidum.
AB  - Soybean isoflavones have been one of the potential preventive candidates for
      antitumor research in recent years. In this paper, we first studied the
      transformation of soybean isoflavones with the homogenized slurry of Ganoderma
      lucidum. The resultant transformed products (TSI) contained (703.21+/-4.35) mg/g
      of genistein, with transformed rates of 96.63% and 87.82% of daidzein and
      genistein, respectively, and TSI also could enrich the bioactive metabolites of
      G. lucidum. The antitumor effects of TSI on human colorectal cancer cell line HTL
      9, human breast cancer cell line MCF-7, and human immortalized gastric epithelial
      cell line GES-1 were also studied. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl
      2-H-tetrazolium bromide (MTT) assay showed that TSI could dramatically reduce the
      viability rates of HTL-9 cells and MCF-7 cells without detectable cytotoxicity on
      GES-1 normal cells when the TSI concentration was lower than 100 MUg/ml. With 100
      MUg/ml of TSI, HTL-9 cells were arrested in the G1 phase, and late-apoptosis was
      primarily induced, accompanied with partial early-apoptosis. TSI could induce
      primarily early-apoptosis by arresting cells in the G1 phase of MCF-7 cells. For
      HTL-9 cells, Western-blot and reverse-transcriptase polymerase chain reaction (RT
      PCR) analysis showed that TSI (100 MUg/ml) can up-regulate the expression of Bax,
      Caspase-3, Caspase-8, and cytochrome c (Cyto-c), indicating that TSI could induce
      cell apoptosis mainly through the mitochondrial pathway. In addition, the
      expression of p53 was up-regulated, while the expression of Survivin and nuclear
      factor kappaB (NF-kappaB) was down-regulated. All these results showed that TSI
      could induce apoptosis of HTL-9 cells by the regulation of multiple apoptosis
      related genes.

PMID- 29204994
TI  - Ophthalmic Application of Anti-VEGF Therapy.

PMID- 29204995
TI  - Prevention of Age-Related Macular Degeneration.
AB  - Age-related macular degeneration (AMD) compromises quality of life. However, the
      available therapeutic options are limited. This has led to the identification of
      modifiable risk factors to prevent the development or alter the natural course
      and prognosis of AMD. The identification and modification of risk factors has the
      potential for greater public health impact on reducing morbidity from AMD.
      Likewise, identifying the imaging clues and genetic clues could serve as a guide
      to recognizing the propensity for progression to severe and end stages of the
      disease. Several attempts, both successful and unsuccessful, have been made for
      interventions that could delay the progression of AMD. Of these, pharmacological
      interventions have shown promising results. The Age-Related Eye Disease Study 1
      and 2 have shown the beneficial role of antioxidants in a selected group of
      patients.

PMID- 29204996
TI  - The VEGF Treatment of AMD Switch Study (The vTAS Study).
AB  - PURPOSE: To evaluate the effect of aflibercept on anatomic and visual outcomes in
      patients with choroidal neovascularization (CNV) previously treated with
      intravitreal ranibizumab with persistent fluid on optical coherence tomography
      (OCT). DESIGN: Prospective, open-label study. METHODS: Eighteen patients (19
      eyes) with CNV being treated with monthly ranibizumab, with persistent fluid on
      OCT, were switched to intravitreal aflibercept injections at intervals of up to 8
      weeks. The primary outcome was the proportion of patients maintaining vision [<5
      letter loss in visual acuity (VA)] at week 48. Secondary outcomes included the
      change in VA and central macular thickness (CMT) and the frequency of treatment
      necessary along with the safety of intravitreal aflibercept. RESULTS: Forty-eight
      weeks after switching to aflibercept, 16/19 eyes had maintained VA. There was a
      median increase in vision of 5 letters [interquartile range (IQR): 0, 15; P =
      0.06)] and median CMT was reduced from 313 um (IQR: 214, 334) to 258 um (IQR:
      200, 299; P = 0.02). After stratification by fluid location the reduction in CMT
      was statistically significant for eyes with intraretinal fluid (IRF) at baseline
      [median change, -25 um (IQR: -14, -64); P = 0.01]. Macular volume within 6 mm of
      the fovea (CMTVol) was significantly reduced in eyes with subretinal fluid (SRF)
      [-0.20 mm3 (IQR: -1.45, -0.05); P = 0.03]. CONCLUSIONS: In this small cohort of
      eyes, switching to aflibercept seemed beneficial. The majority maintained or
      improved vision and eyes with IRF or SRF had significant reductions in macular
      edema. However, visual improvement was not always indicative of anatomical
      improvement.

PMID- 29204997
TI  - [Expression of AQP-1 and AQP-4 in the Lungs of Drown Rats].
AB  - OBJECTIVES: To observe the changes of expression of aquaporin-1(AQP-1) and AQP-4
      in drowned and postmortem immersed rats' lungs. METHODS: Thirty healthy male
      Wistar rats were randomly divided into drowning group, postmortem immersion group
      and cervical dislocation group. The morphological changes of rats' lungs were
      observed using HE staining. The mRNA and protein expressions of AQP-1 and AQP-4
      in rats' lungs were detected by real-time PCR, immunohistochemistry and Western
      blotting, respectively. RESULTS: The results of immunohistochemistry and the
      Western blotting showed that the protein expression of AQP-1 of the drowning
      group was higher than the postmortem immersion group and the cervical dislocation
      group (P<0.05). The result of immunohistochemistry showed that the protein
      expression of AQP-4 of the drowning group was higher than the postmortem
      immersion group and the cervical dislocation group (P<0.05) while no difference
      were detected among the three of them by Western blotting (P>0.05). The mRNA
      expressions of AQP-1 and AQP-4 in rats' lungs of the drowning group was
      significantly higher than the postmortem immersion group (P<0.05). CONCLUSIONS:
      The increase of mRNA and protein expressions of AQP-1 and AQP-4 in lungs of rats
      with cute lung injury of the drowning group would be useful for differentiating
      vital drowning from postmortem immersion.

PMID- 29204998
TI  - [Determination of Bloodstain Age by UV Visible Integrating Sphere Reflection
      Spectrum].
AB  - OBJECTIVES: To establish a method for rapid identification of bloodstain age.
      METHODS: Under laboratory conditions (20 C, 25 C and 30 C), an integrating sphere
      ISR-240A was used as a reflection accessory on an UV-2450 UV-vis
      spectrophotometer, and a standard white board of BaSO4 was used as reference, the
      reflection spectrums of bloodstain from human ears' venous blood were measured at
      regular intervals. The reflection radios R541 and R577 at a specific wavelength
      were collected and the value of R541/R577 was calculated. The linear fitting and
      regression analysis were done by SPSS 17.0. RESULTS: The results of regression
      analysis showed that R2 of the ratios of bloodstain age to UV visible
      reflectivity in specific wavelengths were larger than 0.8 within 8 hours and
      under certain circumstances. The regression equation was established. The
      bloodstain age had significant correlation with the value of R541/R577.
      CONCLUSIONS: The method of inspection is simple, rapid and nondestructive with a
      good reliability, and can be used to identify the bloodstain age within 8 hours
      elapsed-time standards under laboratory conditions.

PMID- 29204999
TI  - [Coronary Angiography in Isolated Hearts and Its Forensic Application].
AB  - OBJECTIVES: To check the isolated heart by coronary angiography to discover the
      location, nature and degree of the coronary artery lesions more accurately and
      increase the comprehensive evaluation ability of cardiovascular disease. METHODS:
      Ten fresh isolated hearts with different causes of death were extracted and
      injected with barium sulphate as contrast substance by ring injector, then
      developed under Xper FD20 angiography equipment. The obtained pictures and image
      data were handled by three-dimensional angiography images with the software
      attached to the angiography equipment. The coronary artery tissues were HE
      stained and observed by microscope. The HE staining results were compared with
      the angiographic results. RESULTS: The imaging data obtained from the 10 cases
      for examination showed 8 cases without coronary artery stenosis and 2 cases with
      III, IV coronary artery stenosis, which were consistent with HE staining results
      of coronary artery organization and the both results were confirmed. CONCLUSIONS:
      Isolated coronary angiography has an unique advantage for accurate grading of
      classification of coronary artery stenosis, examination of vascular malformation
      and tiny lesions, which can provide reference for the localization of small
      lesions and basis during the autopsy for identification conclusion.

PMID- 29205000
TI  - [Distribution of Diatoms in Main Sections of Urban District Rivers with Drowning
      prone in Chengdu].
AB  - OBJECTIVES: To explore the species distribution and constituent ratio of diatoms
      in main sections of urban district rivers where drowning occurs frequently in
      Chengdu. METHODS: Total 39 water samples from the sampling points of 5 rivers
      (Jinjiang, Jinniu, Qingyang, Wuhou and Chenghua districts) in October 2014 were
      collected. The diatoms smear were made and the species distribution and
      constituent ratio of diatoms from the water samples were analyzed using
      biological microscope and acquisition system of digital microscope. RESULTS:
      Total 21 species of diatoms were detected in main sections of urban district
      rivers in Chengdu. Significant differences in the dominant diatom species and
      proportions of the different rivers were observed, and there were different
      species existed in all sampling points of the upstream, midstream and downstream
      of the rivers. CONCLUSIONS: The database of species map, species distribution and
      constituent ratio of diatoms in main sections of urban district rivers in Chengdu
      are preliminarily established, which has special meaning for the analysis and
      evaluation of falling location inference using diatoms test in case
      investigation.

PMID- 29205001
TI  - [Comparision of Different Methods of Area Measurement in Irregular Scar].
AB  - OBJECTIVES: To determine a measurement standard of irregular scar area by
      comparing the advantages and disadvantages of different measurement methods in
      measuring same irregular scar area. METHODS: Irregular scar area was scanned by
      digital scanning and measured by coordinate reading method, AutoCAD pixel method,
      Photoshop lasso pixel method, Photoshop magic bar filled pixel method and Foxit
      PDF reading software, and some aspects of these methods such as measurement time,
      repeatability, whether could be recorded and whether could be traced were
      compared and analyzed. RESULTS: There was no significant difference in the scar
      areas by the measurement methods above. However, there was statistical difference
      in the measurement time and repeatability by one or multi performers and only
      Foxit PDF reading software could be traced back. CONCLUSIONS: The methods above
      can be used for measuring scar area, but each one has its advantages and
      disadvantages. It is necessary to develop new measurement software for forensic
      identification.

PMID- 29205002
TI  - [Application of Multiple Displacement Amplification in Samples with Inhibitors].
AB  - OBJECTIVES: To explore the ability of inhibition resistibility of multiple
      displacement amplification (MDA) in samples with inhibitors. To explain the
      application and value of MDA in forensic medicine by comparing with using
      magnetic beads methods (MBM) to purify sample. METHODS: Different concentrations
      of hemoglobin and humid acid (HA) mixed with DNA samples and then divided the
      samples into MDA group, MBM group and control group. D3S1358 locus was amplified
      and detected by polyacrylamide gel electrophoresis detection system and
      AmpFlSTR(r) IdentifilerTM Plus Kit-capillary electrophoresis detection system.
      RESULTS: When hemoglobin concentrations exceed 1 ng/MUL or HA concentrations
      exceed 0.1 ng/MUL, amplification products could not be obtained by single-locus
      system in control group. When hemoglobin concentration exceeds 100 ng/MUL or HA
      concentrations exceed 1 ng/MUL, the samples could not be amplified by MBM.
      Inhibitors in different concentrations were amplified successfully in MDA group
      without any influence from inhibitors. CONCLUSIONS: MDA has the capability to
      remove the inhibition of hemoglobin and HA, which is better than MBM and has a
      certain value in forensic practices.

PMID- 29205003
TI  - [Forensic Analysis of 25 Cases of Unnatural Death in Custody].
AB  - OBJECTIVES: To screen and collect the cases of unnatural death in custody and
      analyze the influences and forensic characteristics. METHODS: Total 25 cases of
      unnatural death in detainees in custody form 2000 to 2015 were collected. Some
      forensic characteristics such as gender, age, yearly incidence, causes of death,
      manner of death were analyzed. The public security custodies were also compared
      with the prisons. RESULTS: All dead involved were male, mostly were young and
      middle-aged adults. It showed that the number of cases tended to decrease year by
      year. The incidence of the injury cases were higher in public security custodies
      (64.7%) than that in the prisons (12.5%). However, there was a higher suicide
      rate in prisons (62.5%) than that in public security custodies (23.5%). The
      mainly cause of death were injury and asphyxia, there were also some cases died
      from intoxication and electricity. CONCLUSIONS: The cases of unnatural death in
      custody expose some problems such as the imperfectness of law enforcement
      standardization, supervision loopholes and poor medical standards. A
      comprehensive and detailed autopsy has important implications for the
      identification of cause of death in custody.

PMID- 29205004
TI  - [Analysis of Relationship between Injury and Disease in 17 Cases of Cervical
      Trauma with Cervical Vertebra Degeneration].
AB  - OBJECTIVES: To study the characteristics of the relationship between injury and
      disease in forensic identification cases of cervical trauma with cervical
      vertebra degeneration, and to explore the problems about how to identify the
      participation rates of injury and disease using the clinical information,
      forensic examination and imaging examination. METHODS: Seventeen forensic
      identification cases of cervical trauma with cervical vertebra degeneration were
      collected. The age distributions, injury formations, injury severities and
      imaging findings of these cases were analyzed and the relationship between injury
      and disease was evaluated comprehensively. RESULTS: Middle-aged and elderly were
      common in 17 cases and every case was involved with intervertebral disc
      herniation. The main reasons of injuries were hyperextension. The degree of
      injury severity and vertebra degeneration were graded according to the imaging
      findings. The participation rates of injury and disease were also calculated
      comprehensively. CONCLUSIONS: The forensic identification cases of cervical
      trauma with cervical vertebra degeneration should be evaluated with clinical
      information, forensic examination and imaging finding.

PMID- 29205005
TI  - [Forensic Analysis of 95 Nasal Bone Fracture Cases Caused by Blunt Instrument].
AB  - OBJECTIVES: To explore the characteristics of nasal bone fracture caused by blunt
      instrument, including the fracture types, the fracture repair, and the difference
      of manifestations between X-ray and CT. To provide reference for the
      identification. METHODS: The information of basic situation, fracture site,
      injury manner, diagnosis method, expert opinion of 95 adult nasal fracture cases
      caused by blunt object, which occurred in Gutian county of Fujian province from
      January 1999 to December 2013, were analyzed by descriptive statistics. The
      identification conclusions of different injuries were compared according to new
      and old standards as well. RESULTS: There were total 95 adults including 87 male
      and 8 female. The fracture site and quantity have significant correlation with
      the nasal bone anatomical relations and the direction and size of the force.
      Compound fracture was most common. The fracture that could not be determined by X
      ray could be clearly diagnosed by CT examination. According to new and old
      standards, different fracture types have different identification conclusions.
      CONCLUSIONS: There are gender differences in nasal bone fracture cases. Larger
      external force is easy to cause compound fracture. CT examination is
      significantly better than X-ray examination.

PMID- 29205006
TI  - Genetic Polymorphisms of 21 STR Loci in Hunan Province-based Han Population.
AB  - OBJECTIVES: To investigate the genetic polymorphisms of 21 short tandem repeat
      (STR) loci (D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01,
      D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043,
      D8S1179, D5S818, D12S391 and FGA). METHODS: A total of 560 blood samples were
      collected from unrelated healthy individuals of Han population in Hunan Province.
      Chelex-100 extraction method was applied to the extraction of genomic DNA, and an
      AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The
      products were separated and analyzed on 310 Genetic Analyzer. RESULTS: A total of
      248 alleles were observed, the allelic frequencies ranging from 0.001 to 0.518.
      Observation of genotype distributions for each locus showed no deviations from
      Hardy-Weinberg equilibrium except Penta E (P=0.023). The combined power of
      discrimination, combined power of exclusion, and combined matching probability of
      the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999
      998, and 1.36*10-25, respectively. CONCLUSIONS: The 21 STR loci show high
      polymorphisms in the Han population, which can provide valuable data and a
      theoretical basis for forensic individual identification and paternity testing.

PMID- 29205007
TI  - [Research Progress of Carrion-breeding Phorid Flies for Post-mortem Interval
      Estimation in Forensic Medicine].
AB  - It is a difficult problem of forensic medicine to accurately estimate the post
      mortem interval. Entomological approach has been regarded as an effective way to
      estimate the post-mortem interval. The developmental biology of carrion-breeding
      flies has an important position at the post-mortem interval estimation. Phorid
      flies are tiny and occur as the main or even the only insect evidence in
      relatively enclosed environments. This paper reviews the research progress of
      carrion-breeding phorid flies for estimating post-mortem interval in forensic
      medicine which includes their roles, species identification and age determination
      of immatures.

PMID- 29205008
TI  - [Research Progress on Individual Identification Using Forensic Imaging Data under
      the Influence of Evidence Rule].
AB  - With the progress and development of the DNA test and imaging technique, and the
      evolution of evidence rule which bring the discussions about whether the
      individual identification using imaging data is outdated, and other disputes such
      as whether radiologic evidence could be suitable for contemporary evidence and be
      used to solve the posture difference of imaging test. This article summaries the
      domestic and foreign researches of individual identification using imaging data
      in the past 20 years and reviews the problems above.

PMID- 29205009
TI  - [Research Progress on Gene Alterations of Amelogenin Locus in Gender
      Identification].
AB  - There are two kinds of amelogenin gene mutation, including mutation in primer
      binding region of amelogenin gene and micro deletion of Y chromosome encompassing
      amelogenin gene, and the latter is more common. The mechanisms of mutation in
      primer-binding region of amelogenin gene is nucleotide point mutation and the
      mechanism of micro deletion of Y chromosome encompassing amelogenin gene maybe
      non-allelic homologous recombination or non-homologous end-joining. Among the
      population worldwide, there is a notably higher frequency of amelogenin gene
      mutations in Indian population, Sri Lanka population and Nepalese population
      which reside within the Indian subcontinent. Though amelogenin gene mutations
      have little impact on fertility and phenotype, they might cause incorrect result
      in gender identification. Using composite-amplification kit which including
      autosomal STR locus, amelogenin gene locus and multiple Y-STR locus, could avoid
      wrong gender identification caused by amelogenin gene mutation.

PMID- 29205010
TI  - Boomerang-shaped hemorrhage of the splenium of corpus callosum after mild brain
      injury. An unusual case of delayed hematoma.

PMID- 29205011
TI  - Clinical correlates of subventricular zone-contacting glioblastomas: a meta
      analysis.
AB  - INTRODUCTION: The clinical and molecular correlates of glioblastomas (GBMs)
      contacting the subventricular zone (SVZ+ GBM) are unknown. We aimed to reveal any
      such correlates that may help explain their increased GBM malignancy. EVIDENCE
      ACQUISITION: A meta-analysis was, therefore, conducted to assess whether tumor's
      MGMT promoter methylation status, IDH mutation status, volume, and extent of
      resection as well as patients' age at diagnosis and preoperative Karnofsky
      performance status score (KPS) correlate with SVZ contact by GBM. In addition,
      available imaging of GBM patients in The Cancer Imaging Archive was assessed for
      SVZ contact and their corresponding clinical and molecular variables were
      obtained through The Cancer Genome Atlas (TCGA) database. EVIDENCE SYNTHESIS:
      Twenty-one studies were identified through PubMed and EMBASE database search. 257
      patients who had imaging were included from the TCIA/TCGA database. MGMT promoter
      methylation status (summary odds ratio, OD, 1.18 [0.84-1.66], p=0.34), IDH
      mutation status (OD: 0.63 [0.20-1.99], p=0.43), and patients' age of diagnosis
      (summary mean difference, MD, 0.10 years [-1.85, 2.05], p=0.92) did not
      associated with SVZ contact of the GBM. However, SVZ+ GBMs were significantly
      larger than SVZ- GBMs (MD: 17.3 cm3 [8.70-25.8], p<0.0001). SVZ+ GBM patients had
      lower KPS scores (MD: -3.33 [-5.31-(-1.35)], p=0.001) and were half as likely to
      receive a gross total resection (OD: 0.50 [0.40-0.64], p<0.00001). CONCLUSIONS:
      Additional, large studies that rigorously control for all the known clinical and
      molecular prognosticators, especially extent of resection and preoperative KPS
      scores, are needed to evaluate whether SVZ contact by GBM independently
      influences survival.

PMID- 29205012
TI  - Evaluation of the different surgical parathyroidectomies on secondary
      hyperparathyroidism in uremia patients.

PMID- 29205013
TI  - Study on regulation of adipokines on body fat distribution and its correlation
      with metabolic syndrome in type 2 diabetes mellitus.
AB  - BACKGROUND: This paper aims to investigate the regulating role of adipokine
      expression level in body fat distribution of patients with type 2 diabetes
      mellitus (T2MD) as well as its correlation with metabolic syndrome (MS). METHODS:
      140 patients with T2MD admitted in the Endocrinology Department of the First
      Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from
      January 2017 to July 2017 were selected; their body height and weight were
      measured to calculate body mass index (BMI); patients with a BMI <=23.9 kg/m2
      were included into control group (n=49), and those with a BMI >=24 kg/m2 into
      observation group (n=91). Based on whether the patients were complicated with MS,
      they were divided into non-metabolic syndrome (N-MS) group (n=79) and MS group
      (n=61); the levels of serum dipeptidyl peptidase-4 (DPP-4), adiponectin (ADPN)
      and leptin as well as the contents of body fat and lean tissue of the two groups
      of patients were measured. RESULTS: The serum DPP-4 level in observation group
      was remarkably elevated compared with that in control group (p<0.05), but there
      were no significant differences in the leptin and ADPN levels between the two
      groups (p>0.05). The serum DPP-4 and leptin levels were positively correlated
      with the total body fat mass (FAT) of the patients in observation group (r=0.461,
      p=0.004; r=0.433, p=0.007); DPP-4 level had a positive correlation with trunk fat
      mass (TRUNK F) (r=0.545, p=0.001) and limb fat mass (LIMB F) (r=0.412, p=0.005);
      the leptin level was positively correlated with LIMB F (r=0.513, p=0.001); the
      leptin and ADPN levels were negatively correlated with the content of lean tissue
      (r=-0.476, p=0.001; r=-0.344, p=0.021). Compared with those in N-MS group, the
      levels of serum DPP-4 and leptin were increased significantly, while the ADPN
      level was decreased notably (p<0.05) in MS group. CONCLUSIONS: The adipokines DPP
      4 and leptin in the serum can influence the body fat distribution of patients
      with T2MD; there is an important association of DPP-4, leptin and ADPN levels
      with MS, which may be used as therapeutic targets for multiple metabolism
      disorders of T2MD.

PMID- 29205014
TI  - High intensity focused ultrasound (HIFU) in tumor therapy.
AB  - HIFU (high intensity focused ultrasound) is a method in which high-frequency
      ultrasound is focused on a tissue in order to achieve a thermal effect and the
      subsequent percutaneously ablation, or tissue modulation. HIFU is non-invasive
      and results in an immediate tissue destruction effect corresponding to surgery,
      either percutaneously or through body cavities. HIFU can be utilized in the
      treatment of both benign and malignant tumors. In neurological diseases, focused
      HIFU can be used in the treatment of disorders of the basal ganglia.

PMID- 29205015
TI  - Treatment options for acute mesenteric ischemia have improved.
AB  - Acute mesenteric ischemia resulting from mesenteric arterial thrombosis is a life
      threatening cardiovascular complication with symptoms ranging from sudden-onset
      abdominal pain to vague symptoms of several days' duration. Although contrast
      enhanced computed tomography is an excellent diagnostic tool, detection of the
      disease before the development of permanent intestinal injury is still difficult.
      Endovascular treatment is usually successful in restoring intestinal blood flow
      acutely. Chronic mesenteric ischemia requires urgent detection and therapy in
      order to prevent irreversible intestinal ischemia.

PMID- 29205016
TI  - Pediatric ocular disorders and visual handicap in Finland - what do the registers
      tell?
AB  - INTRODUCTION: There is no published data from the last few years on the frequency
      of pediatric ocular disorders and visual handicap in Finland. METHODS: We
      surveyed the registers of THL (National Institute for Health and Welfare) and
      statistics of Kela (The Social Insurance Institution of Finland). RESULTS: The
      majority of visual defects are neurologic or congenital. Retinopathic lesions
      were reported in 11% of small premature infants. In the years from 1993 to 2011,
      significant abnormalities of the eye or its accessory organs were on the average
      registered annually in 94 liveborn infants, and the number of corresponding
      cancers was less than five. CONCLUSIONS: Ocular disorders in children are rare.
      They are significant because of the special attention required in everyday life.

PMID- 29205018
TI  - Update on current care guideline: Cytological changes in the cervix, vagina and
      vulva.
AB  - Annually approximately 160 new cervical cancers are diagnosed in Finland.
      Screening has decreased both incidence and mortality by 80%. Both primary HPV
      testing and Pap smear can be used in screening. In the future HPV vaccination
      will decrease the number of cervical cancers. Abnormal findings in Pap smears
      indicate management. LSIL lesions are followed up especially among young women
      and HSIL lesions treated. Follow-up after treatment should be reliably arranged,
      because increased risk of cancer remains ever after treatment.

PMID- 29205017
TI  - Drip-and-ship stroke thrombolysis in the emergency department of a healthcare
      center - a possibility for those fallen ill in rural settings.
AB  - Thrombolysis with tissue plasminogen activator is the mainstay in the treatment
      of acute stroke. Reducing the delay of thrombolysis treatment improves patient
      prognosis and reduces the incidence of complications. Variable telestroke
      regimens have improved the availability of stroke thrombolysis, especially in
      rural settings, where neurologists are not readily available. In the drip-and
      ship strategy, stroke thrombolysis is initiated in a peripheral hospital and the
      patient is then transferred to a tertiary care unit. We report the first case of
      drip-and-ship stroke thrombolysis in a rural health care center in Northeastern
      Finland.

PMID- 29205019
TI  - Healthy habits - healthy brain.
AB  - A multifactorial memory disease with old-age onset forms a continuum having at
      one end a "clear" Alzheimer-type form, with a pathophysiology involving a central
      role played by the accumulation of amyloid protein, and a purely arterial disease
      at the other end. Most of the cases exhibit a mixed form. As the options of
      prevention of arterial diseases are well known, this will also provide
      possibilities for extensive prevention of memory diseases. Central measures
      include physical activity, a healthy diet and intervention in risk factors -
      early enough, of course. What is good for the heart is generally good for the
      brain as well.

PMID- 29205020
TI  - "Genetic code" of brain ageing.
AB  - Neurons are more susceptible than other cells to the effects of ageing, since
      most of them are not capable of dividing, and they consume plenty of energy. In
      the "genetic code of brain ageing", central role is played by the genes that
      regulate the risk of Alzheimer's disease and vascular diseases. Genes have been
      recognized underlying memory disorders and longevity. Genetic studies have
      revealed metabolic routes, including fat and energy metabolism, that can be
      influenced by an individual through living habits, and also through structures
      maintaining social activity.

PMID- 29205021
TI  - Health mind in a health brain.
AB  - The last few years have seen an increase in the research of psychic well-being
      and positive mental health. A positive point of view refers not only to pleasure
      but also to the ability to act in a constructive manner in challenging
      situations, and effectively regulate negative feelings and stress. Although a
      positive state of mind is often a passing experience, it can also be developed.
      Analogously, effective methods tested in a controlled manner have been
      established for the development of positive capabilities. It is furthermore
      possible to promote psychic well-being through exercise, healthy diet and
      practicing mindfulness.

PMID- 29205022
TI  - Changing world, changing old age.
AB  - Every fifth Finn has turned 65. Most of them live an active life that does not
      differ from that of the working-age population. Long-term illnesses and the
      resulting disability are accumulating to the late senescence. The need for help
      from other people and the resulting financial pressures on municipalities are
      targeted to the elderly having a memory disorder as one of their diseases. Is
      normal old age thus disappearing, and will the group of those having lost their
      brain health and requiring care be the only thing that is left from old age?

PMID- 29205023
TI  - Graft-versus-host disease in stem cell transplantation.
AB  - Graft-versus-host disease (GvHD) remains a major treatment-related risk in
      patients undergoing stem cell transplantation. Although advances in HLA-typing
      and graft types have reduced the risk of GvHD, a breakthrough in the treatment of
      severe GvHD is still lacking. Allogenic stem cell transplant has potentially
      beneficial immunological effects on the malignant disease necessitating
      transplantation, and the importance of these effects must be considered when
      treating GvHD.

PMID- 29205024
TI  - Disorders of DNA repair mechanisms and their clinical significance.
AB  - DNA repair mechanisms maintain genome stability by preventing the multiplication
      of genetic errors, caused by environmental factors and intracellular processes,
      during cell division. Unrepaired damage may permanently alter genome and cell
      functions, and even minor changes in DNA strand may initiate malignant
      transformation of the cell. Up to 25 000 changes in DNA are occur daily in a
      single, actively dividing, cell, and these changes are continuously repaired. If
      DNA repair mechanisms are impaired, errors will accumulate into the genome. As
      numerous factors of different nature can cause genetic errors, and thus several
      different DNA repair mechanisms are necessary to ensure genomic stability.

PMID- 29205025
TI  - Can we prevent post-ERCP pancreatitis?
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is the primary method for
      treating cholestasis and biliary tract gallstones. Although noninvasive imaging
      has replaced ERCP in diagnostics, ERCP remains the mainstay in collecting
      diagnostic specimens from the biliary tract. ERCP carries a risk of post-ERCP
      pancreatitis, which can vary from mild to life-threatening. Difficult cannulation
      is the most important risk factor for pancreatitis. Careful patient selection and
      adequate endoscopy training are the foundation of safe ERCP practice. Current
      evidence supports the routine use of prophylactic rectal NSAID in all patients to
      prevent post-ERCP pancreatitis.

PMID- 29205026
TI  - Prevalence, risk factors and prognosis of depressive disorders.
AB  - In Finland, one out of ten adults had a depressive disorder on 2011, and compared
      to year 2000, the prevalence increased especially in women. Risk factors for
      recurrent depressive episodes included female gender, young age, childhood
      adversities, and prior mild depressive symptoms. During follow-up, 75% of
      patients recovered, and the risk for prolonged depression was increased in those
      living alone or with severe symptoms. Depressive disorders are associated with a
      two-fold risk of death, which can only partly be explained by physical illness
      and negative health behavior.

PMID- 29205027
TI  - Dysmenorrhea in teenagers.
AB  - Dysmenorrhea affects quality of life, but is often inadequately treated in
      teenagers. The mainstay of treatment is NSAID, which must be started pre
      emptively and in adequate dose. If NSAID provides insufficient pain relief, or
      when contraception is required, combined oral contraceptives can be prescribed
      concomitantly. Hormonal IUD can also be used in teenagers. If dysmenorrhea
      persists despite appropriate treatment, the patient must be referred to a
      gynecologist. Endometriosis, the most common cause of severe dysmenorrhea, can
      manifest already during adolescence.

PMID- 29205028
TI  - Clustered-Microcapsule-Shaped Microporous Carbon-Coated Sulfur Composite
      Synthesized via in Situ Oxidation.
AB  - Hollow materials as sulfur hosts have been intensively investigated to address
      the poor cycling stabilities of Li-S batteries. Herein, we report an enhanced
      hollow framework to improve the applicability of the sulfur confinement. A
      clustered-microcapsule-shaped microporous carbon coated sulfur (CM-S@MPC)
      composite is prepared from the clustered zinc sulfide precursor, through an in
      situ oxidation process. The high specific surface area and the in situ
      preparation guarantee the uniform distribution of sulfur inside the carbon
      microcapsule, even under a higher sulfur content of 83 wt %. In addition, the
      interconnected frame constructed by the stacking of carbon microcapsules also
      mitigates the lithium polysulfide loss by setting interlayered hurdles on their
      pathway along the outward diffusion. Hence, these enable a full demonstration of
      excellent cycling stability, compared to the control sample obtained via physical
      sulfur infiltration. The outstanding decay rate of 0.039% per cycle is achieved
      during 700 cycles at 1 C, even under high sulfur loading.

PMID- 29205029
TI  - Supramolecular Nanomedicine Constructed from Cucurbit[8]uril-Based Amphiphilic
      Brush Copolymer for Cancer Therapy.
AB  - An amphiphilic supramolecular brush copolymer CB[8]?(PEG-Np.PTPE) was constructed
      on the basis of a novel host-guest molecular recognition model formed by
      cucurbit[8]uril (CB[8]), 4,4'-bipyridinium derivative, and PEGylated naphthol
      (PEG-Np). In aqueous solution, the resultant supramolecular brush copolymer self
      assembled into supramolecular nanoparticles (SNPs), by which the anticancer drug
      doxorubicin (DOX) was encapsulated in the hydrophobic core, establishing an
      artful Forster resonance energy transfer system with dual fluorescence quenched.
      With the help of intracellular reducing agents and low pH environment, the SNPs
      disassembled and the loaded drug molecules were released, realizing in situ
      visualization of the drug release via the location and magnitude of the energy
      transfer-dependent fluorescence variation. The cytotoxicity evaluation indicated
      DOX-loaded SNPs effectively inhibited cell proliferation against HeLa cells.
      Animal experiments demonstrated that these DOX-loaded SNPs highly accumulated in
      tumor tissues through the enhanced permeability and retention effect and also had
      a long blood circulation time. These multifunctional supramolecular nanoparticles
      possessing self-imaging and controllable drug release ability exhibited great
      potential in cancer therapy.

PMID- 29205030
TI  - Crack-Enhanced Microfluidic Stretchable E-Skin Sensor.
AB  - We reported the development of a transparent stretchable crack-enhanced
      microfluidic capacitive sensor array for use in E-skin applications. The
      microfluidic sensor was fabricated through a simple lamination process involving
      two silver nanowire (AgNW)-embedded rubbery microfluidic channels arranged in a
      crisscross fashion. The sensing performance was optimized by testing a variety of
      sensing liquids injected into the channels. External mechanical stimuli applied
      to the sensor induced the liquid to penetrate the deformed microcracks on the
      rubber channel surface. The increased interfacial contact area between the liquid
      and the nanowire electrodes increased the capacitance of the sensor. The device
      sensitivity was strongly related to both the initial fluid interface between the
      liquid and crack wall and the change in the contact length of the liquid and
      crack wall, which were simulated using the finite element method. The
      microfluidic sensor was shown to detect a wide range of pressures, 0.1-140 kPa.
      Ordinary human motions, including substantial as well as slight muscle movements,
      could be successively detected, and 2D color mappings of simultaneous external
      load sensing were collected. Our simple method of fabricating the microfluidic
      channels and the application of these channels to stretchable e-skin sensors
      offers an excellent sensing platform that is highly compatible with emerging
      medical and electronic applications.

PMID- 29205031
TI  - Effect of Shewanella oneidensis on the Kinetics of Fe(II)-Catalyzed
      Transformation of Ferrihydrite to Crystalline Iron Oxides.
AB  - Iron (oxyhydr)oxides are widespread in natural and engineered systems, potent
      adsorbents of contaminants and a source of energy for iron-reducing bacteria.
      Microbial reduction of iron (oxyhydr)oxides results in the formation of Fe(II)
      which can induce the transformation of these iron minerals, typically from less
      crystalline to more crystalline forms, affecting the biogeochemical cycling of
      iron and the behavior of any species adsorbed to the iron (oxyhydr)oxides.
      Factors influencing the transformation rate of the poorly crystalline iron
      (oxyhydr)oxide, ferrihydrite, to more crystalline forms in the presence of the
      iron reducing bacterium Shewanella oneidensis MR-1 are investigated under
      controlled laboratory conditions in this work. In particular, the amount of
      Fe(II) produced increased the transformation rate while increasing concentrations
      of the electron donor, lactate, decreased the rate. Using kinetic parameters
      determined from abiotic controls, the results of transformation experiments in
      the presence of Shewanella oneidensis were modeled with this exercise revealing
      that less goethite and more lepidocrocite formed than expected. Conversely,
      studies using the Shewanella exudate only, containing biogenic Fe(II), displayed
      rates of transformation that were satisfactorily modeled using these abiotic
      control kinetic parameters. This result suggests that the physical presence of
      the microbes is pivotal to the reduction in ferrihydrite transformation rate
      observed in the biotic experiments relative to the analogous abiotic controls.

PMID- 29205033
TI  - Acid-Responsive Conductive Nanofiber of Tetrabenzoporphyrin Made by Solution
      Processing.
AB  - While cofacial one-dimensional (1-D) pi stacking of a planar aromatic molecule is
      ideal for the construction of conduction systems, such molecules, including
      tetrabenzoporphyrin (BP), prefer to form edge-to-face stacking through CH-pi
      interactions. We report here that the BP molecules spontaneously form a 1-D
      cofacial stack in chloroform containing 1% trifluoroacetic acid (TFA) and that a
      bundle of the formed nanofiber shows acid-responsive 1-D conductivity as high as
      1904 S m-1. A small fraction (2.7%) of BP in the fiber exists in a cation radical
      state, and 1.5 equiv of TFA is located in an intercolumnar void. Dedoping and
      redoping of TFA with trimethylamine vapor results in 1300-2700-fold decreases and
      increases, respectively, in the conductivity and also the amount of the radical
      cation. The conductivity of the fiber also shows a correlation with the pKa of
      acid dopants.

PMID- 29205032
TI  - Apratyramide, a Marine-Derived Peptidic Stimulator of VEGF-A and Other Growth
      Factors with Potential Application in Wound Healing.
AB  - A novel linear depsipeptide enriched with tyrosine-derived moieties, termed
      apratyramide, was isolated from an apratoxin-producing cyanobacterium. The
      structure was determined using a combination of NMR spectroscopy, mass
      spectrometry, and chiral analysis of the acid hydrolyzate and confirmed by total
      synthesis. Apratyramide up-regulated multiple growth factors at the transcript
      level in human keratinocyte (HaCaT) cells and induced the secretion of vascular
      endothelial growth factor A (VEGF-A) from HaCaT cells, suggesting the compound's
      potential wound-healing properties through growth factor induction. Transcriptome
      analysis and sequential validation supported the hypothesis and indicated its
      mode of action (MOA) through the unfolded protein response (UPR) pathway, which
      is functionally related to wound healing and angiogenesis. The conditioned medium
      of HaCaT cells treated with apratyramide induced angiogenesis in vitro. An ex
      vivo rabbit corneal epithelial model was applied to confirm the VEGF-A induction
      in this wound-healing model.

PMID- 29205035
TI  - Selective Transport through Membranes with Charged Nanochannels Formed by
      Scalable Self-Assembly of Random Copolymer Micelles.
AB  - Membranes that can separate compounds based on molecular properties can
      revolutionize the chemical and pharmaceutical industries. This study reports
      membranes capable of separating organic molecules of similar size based on their
      electrostatic charge. These membranes feature a network of carboxylate
      functionalized 1-3 nm nanochannels, manufactured by a simple, scalable coating
      process: a porous support is coated with a packed array of polymer micelles in
      alcohol, formed by the self-assembly of a water-insoluble random copolymer with
      fluorinated and carboxyl functional repeat units. The interstices between these
      micelles serve as charged nanochannels through which water and solutes can pass.
      The negatively charged carboxylate groups lead to high separation selectivities
      between organic solutes of similar size but different charge. In single-solute
      diffusion experiments, neutral solutes permeate up to 263 times faster than
      negatively charged compounds of similar size. This selectivity is further
      enhanced in experiments with mixtures of these solutes. No permeation of the
      anionic compound was observed for over 24 h. In filtration experiments, these
      membranes separate anionic and neutral organic compounds while exhibiting water
      fluxes comparable to that of commercial membranes. Furthermore, carboxylate
      groups can be functionalized, creating membranes with nanopores with customizable
      functionality to enable a broad range of selective separations.

PMID- 29205034
TI  - Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells
      by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor
      Antagonist.
AB  - The most common solid tumors show intrinsic multidrug resistance (MDR) or
      inevitably acquire such when treated with anticancer drugs. In this work, we
      describe the discovery of a peripherally restricted, potent, competitive NMDA
      receptor antagonist 1l by a structure-activity study of the broad-acting
      ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l
      augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma
      cells. The underlying biological mechanism was shown to be interference with the
      lipid signaling pathway, leading to reduced expression of MDR transporters and
      thereby an increased accumulation of sorafenib in the cancer cells. Interference
      with lipid signaling pathways by NMDA receptor inhibition is a novel and
      promising strategy for reversing transporter-mediated chemoresistance in cancer
      cells.

PMID- 29205037
TI  - I2-Catalyzed Oxidative Amidation of Benzylamines and Benzyl Cyanides under Mild
      Conditions.
AB  - We report a novel and efficient method for the oxidation of benzylic carbons
      (amines and cyanides) into corresponding benzamides using a catalytic amount of
      I2 and TBHP as the green oxidant via the C-H bond cleavage of the benzylic carbon
      under mild reaction conditions. According to the literature survey, this is the
      first report for the oxidative amidation of benzylamines and decyanation of
      benzyl cyanides in one pot under metal-free conditions.

PMID- 29205036
TI  - Metabolic Profile of Zearalenone in Liver Microsomes from Different Species and
      Its in Vivo Metabolism in Rats and Chickens Using Ultra High-Pressure Liquid
      Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry.
AB  - To explore differences of zearalenone (ZEN) metabolism between various species,
      phase I and II metabolism by liver microsomes of animals and human were
      investigated using ultra high-pressure liquid chromatography-quadrupole/time-of
      flight mass spectrometry (UHPLC-Q/TOF MS). A total of 24 metabolites were
      identified, among which 12 were reported for the first time. Reduction,
      hydroxylation, and glucuronidation were the major metabolic pathways of ZEN, and
      significant differences in various species were also observed. Reduction was the
      main reaction in swine and human, whereas hydroxylation was predominant in rats,
      chickens, goats, and cows in in vitro systems. Furthemore, in vivo metabolism of
      ZEN in rats and chickens was investigated, and 23 and 6 metabolites were
      identified in each species, respectively. Reduction, hydroxylation, and
      glucuronidation were the major metabolic pathways in rats, while reduction and
      sulfation predominated in chickens. These results further enrich the
      biotransformation profile of ZEN, providing a helpful reference for assessing the
      risks to animals and humans.

PMID- 29205038
TI  - Metabolic Changes during Storage of Brassica napus Seeds under Moist Conditions
      and the Consequences for the Sensory Quality of the Resulting Virgin Oil.
AB  - Virgin rapeseed (Brassica napus) oil is a valuable niche product, if delivered
      with a high quality. In this study, the effects of moist storage of B. napus
      seeds for 1 to 4 days on the seed metabolome and the chemo-sensory properties of
      the produced oils were determined. The concentrations of several primary
      metabolites, including monosaccharides and amino acids, rapidly increased in the
      seeds, probably indicating the breakdown of storage compounds to support seed
      germination. Seed concentrations of indole glucosinolates increased with a slight
      time offset suggesting that amino acids may be used to modify secondary
      metabolism. The volatile profiles of the oils were pronouncedly influenced by
      moist seed storage, with the sensory quality of the oils decreasing. This study
      provides a direct time-resolved link between seed metabolism under moist
      conditions and the quality of the resulting oils, thereby emphasizing the crucial
      role of dry seed storage in ensuring high oil quality.

PMID- 29205039
TI  - Comparison of Two Static in Vitro Digestion Methods for Screening the
      Bioaccessibility of Carotenoids in Fruits, Vegetables, and Animal Products.
AB  - In vitro digestion methods are routinely used to assess the bioaccessibility of
      carotenoids and other dietary lipophilic compounds. Here, we compared the
      recovery of carotenoids and their efficiency of micellarization in digested
      fruits, vegetables, egg yolk, and salmon and also in mixed-vegetable salads with
      and without either egg yolk or salmon using the static INFOGEST method22 and the
      procedure of Failla et al.16 Carotenoid stability during the simulated digestion
      was >=70%. The efficiencies of the partitioning of carotenoids into mixed
      micelles were similar when individual plant foods and salad meals were digested
      using the two static methods. Furthermore, the addition of cooked egg or salmon
      to vegetable salads increased the bioaccessibility of some carotenoids. Our
      findings showed that the two methods of in vitro digestion generated similar
      estimates of carotenoid retention and bioaccessibility for diverse foods.

PMID- 29205040
TI  - A New Method of Constructing a Drug-Polymer Temperature-Composition Phase Diagram
      Using Hot-Melt Extrusion.
AB  - Current experimental methodologies used to determine the thermodynamic solubility
      of an API within a polymer typically involves establishing the
      dissolution/melting end point of the crystalline API within a physical mixture or
      through the use of the glass transition temperature measurement of a demixed
      amorphous solid dispersion. The measurable "equilibrium" points for solubility
      are normally well above the glass transition temperature of the system, meaning
      extrapolation is required to predict the drug solubility at pharmaceutically
      relevant temperatures. In this manuscript, we argue that the presence of highly
      viscous polymers in these systems results in experimental data that exhibits an
      under or overestimated value relative to the true thermodynamic solubility. In
      previous work, we demonstrated the effects of experimental conditions and their
      impact on measured and predicted thermodynamic solubility points. In light of
      current understanding, we have developed a new method to limit error associated
      with viscosity effects for application in small-scale hot-melt extrusion (HME).
      In this study, HME was used to generate an intermediate (multiphase) system
      containing crystalline drug, amorphous drug/polymer-rich regions as well as drug
      that was molecularly dispersed in polymer. An extended annealing method was used
      together with high-speed differential scanning calorimetry to accurately
      determine the upper and lower boundaries of the thermodynamic solubility of a
      model drug-polymer system (felodipine and Soluplus). Compared to our previously
      published data, the current results confirmed our hypothesis that the prediction
      of the liquid-solid curve using dynamic determination of dissolution/melting end
      point of the crystalline API physical mixture presents an underestimation
      relative to the thermodynamic solubility point. With this proposed method, we
      were able to experimentally measure the upper and lower boundaries of the liquid
      solid curve for the model system. The relationship between inverse temperature
      and drug-polymer solubility parameter (chi) remained linear at lower drug
      loadings. Significantly higher solubility and miscibility between the felodipine
      Soluplus system were derived from the new chi values.

PMID- 29205041
TI  - Metal-Free Diaryl Etherification of Tertiary Amines by Ortho-C(sp2)-H
      Functionalization for Synthesis of Dibenzoxazepines and -ones.
AB  - A phenyliodine(III) diacetate mediated umpolung reactivity of the tertiary amines
      with suitably substituted o-hydroxybenzyl and phenyl groups is exploited to
      facilitate o-C(sp2)-H functionalization to afford diaryl ethers. The presence of
      an o-CHO and secondary amine functionalities in the resulting diaryl ether,
      generated in situ, were utilized for synthesis of dibenzoxazepines and
      dibenzoxazepinones. Mild conditions and relative broad substrate scope, and
      potential for further diversification of the diaryl ethers are highlights of this
      methodology.

PMID- 29205042
TI  - Synthesis of Oligo-(alkyne-triplet)peptide Constructs.
AB  - Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click synthesis of an Fmoc
      (trispropargyl)amino acid building block for solid phase peptide synthesis (SPPS)
      of oligo-(trialkyne)peptide constructs is reported. These can carry potentially
      indefinite numbers of inherent alkyne-triplets, which are click derivatized with
      GlcNAc-azide into the corresponding glycopeptides.

PMID- 29205043
TI  - Total Synthesis of (+)-Gliocladin C Based on One-Pot Construction of a 3a-(3
      Indolyl)pyrroloindoline Skeleton by Sulfonium-Mediated Cross-Coupling of
      Tryptophan and Indole.
AB  - Total synthesis of (+)-gliocladin C has been achieved on the basis of one-pot
      construction of the 3a-(3-indolyl)pyrroloindoline core structure by the cross
      coupling of a tryptophan derivative and an indole promoted by a sulfonium species
      generated from dialkylsulfoxide and triflic anhydride.

PMID- 29205044
TI  - Direct Decarboxylative-Decarbonylative Alkylation of alpha-Oxo Acids with
      Electrophilic Olefins via Visible-Light Photoredox Catalysis.
AB  - The decarbonylation of primary, secondary, and tertiary alkyl-substituted acyl
      radicals has been investigated through photoredox catalysis. A series of
      quaternary carbons and gamma-ketoesters have been directly constructed by the
      photoredox 1,4-conjugate addition of the corresponding alkyl ketoacids with
      electrophilic alkenes. And, the tertiary alkyl ketoacids have proved to be good
      precursors of tertiary alkyl radicals.

PMID- 29205045
TI  - Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and
      Systemic Metabolic Dysfunction in a Septic Rat Model.
AB  - The colon ascendens stent peritonitis (CASP) surgery induces a leakage of gut
      contents, causing polymicrobial sepsis related to post-operative multiple organ
      failure and death in surgical patient. To evaluate the effects of CASP on
      multiple organs, we analyzed the systemic metabolic consequences in liver,
      kidney, lung, and heart of rats after CASP by employing a combination of
      metabolomics, clinical chemistry, and biological assays. We found that CASP
      surgery after 18 h resulted in striking elevations of lipid, amino acids,
      acetate, choline, PC, and GPC in rat liver together with significant depletion of
      glucose and glycogen. Marked elevations of organic acids including lactate,
      acetate, and creatine and amino acids accompanied by decline of glucose, betaine,
      TMAO, choline metabolites (PC and GPC) nucleotides, and a range of organic
      osmolytes such as myo-inositol are observed in the kidney of 18 h post-operative
      rat. Furthermore, 18 h post-operative rats exhibited accumulations of lipid,
      amino acids, and depletions of taurine, myo-inositol, choline, PC, and GPC and
      some nucleotides including uridine, inosine, and adenosine in the lung. In
      addition, significant elevations of some amino acids, uracil, betaine, and
      choline metabolites, together with depletion of inosine-5'-monophosphate, were
      only observed in the heart of 18 h post-operative rats. These results provide new
      insights into pathological consequences of CASP surgery, which are important for
      timely prognosis of sepsis.

PMID- 29205046
TI  - Substituent-Directed Regioselective Azidation: Copper-Catalyzed C-H Azidation and
      Iodine-Catalyzed Dearomatizative Azidation of Indole.
AB  - Azidation of indoles using iodine and copper bromide as catalysts under ambient
      reaction conditions is presented. The regioselectivity is directed by the
      substituent at the C3-position of indole. A radical stabilizing group such as an
      ester or ketone moiety at the C3-position of indole leads to azidation at the C2
      position, whereas a less radical stabilizing group such as an alkyl or amide
      group at the C3-position of indole furnishes the 3-azidooxindole product. This
      protocol is mild and efficient to obtain several 2-azidoindole derivatives and 3
      azidooxindole derivatives in moderate to good yields. The reaction conditions
      hold well for gram-scale synthesis.

PMID- 29205047
TI  - ICRP Publication 136: Dose Coefficients for Non-human Biota Environmentally
      Exposed to Radiation.
AB  - Abstract -: The diversity of non-human biota is a specific challenge when
      developing and applying dosimetric models for assessing exposures of flora and
      fauna from radioactive sources in the environment. Dosimetric models, adopted in
      Publication 108, provide dose coefficients (DCs) for a group of reference
      entities [Reference Animals and Plants (RAPs)]. The DCs can be used to evaluate
      doses and dose rates, and to compare the latter with derived consideration
      reference levels (DCRLs), which are bands of dose rate where some sort of
      detrimental effect in a particular RAP may be expected to occur following
      chronic, long-term radiation exposure, as outlined in Publication 124. These
      dosimetric models pragmatically assume simple body shapes with uniform
      composition and density, homogeneous internal contamination, limited sets of
      idealised sources of external exposure to ionising radiation for aquatic and
      terrestrial animals and plants, and truncated radioactive decay chains. This
      pragmatic methodology is further developed and systematically extended in this
      publication, which supersedes the DC values of Publication 108. Significant
      methodological changes since Publication 108 include: implementation of a new
      approach for external exposure of terrestrial animals with an extended set of
      environmental radioactive sources in soil and in air; considering an extended
      range of organisms and locations in contaminated terrain; transition to the
      contemporary radionuclide database of Publication 107; assessment-specific
      consideration of the contribution of radioactive progeny to DCs of parent
      radionuclides; and use of generalised allometric relationships in the estimation
      of biokinetic or metabolic parameter values. These methodological developments
      result in changes to previously published tables of DCs for RAPs, and revised
      values are provided in this publication. This publication is complemented by a
      new software tool, called 'BiotaDC', which enables the calculation of DCs for
      internal and external exposures of organisms with user-defined masses, shapes,
      and locations in the environment and for all radionuclides in Publication 107.

PMID- 29205048
TI  - Electroconvulsive therapy stimulus titration: Not all it seems.
AB  - OBJECTIVE: To examine the provenance and implications of seizure threshold
      titration in electroconvulsive therapy. BACKGROUND: Titration of seizure
      threshold has become a virtual standard for electroconvulsive therapy. It is
      justified as individualisation and optimisation of the balance between efficacy
      and unwanted effects. RESULT: Present day threshold estimation is significantly
      different from the 1960 studies of Cronholm and Ottosson that are its usual
      justification. The present form of threshold estimation is unstable and too
      uncertain for valid optimisation or individualisation of dose. Threshold
      stimulation (lowest dose that produces a seizure) has proven therapeutically
      ineffective, and the multiples applied to threshold to attain efficacy have never
      been properly investigated or standardised. The therapeutic outcomes of threshold
      estimation (or its multiples) have not been separated from simple dose effects.
      Threshold estimation does not optimise dose due to its own uncertainties and the
      different short-term and long-term cognitive and memory effects. Potential harms
      of titration have not been examined. CONCLUSION: Seizure threshold titration in
      electroconvulsive therapy is not a proven technique of dose optimisation. It is
      widely held and practiced; its benefit and harmlessness assumed but unproven. It
      is a prematurely settled answer to an unsettled question that discourages further
      enquiry. It is an example of how practices, assumed scientific, enter medicine by
      obscure paths.

PMID- 29205049
TI  - Extracorporeal Shockwave Lithotripsy Could Lead to a Prolonged Increase in the
      Renal Fibrotic Process of Up to 2 Years.
AB  - INTRODUCTION AND OBJECTIVE: This prospective study aimed to evaluate the effect
      of ramping and pause protocols on renal fibrosis, blood pressure control, and
      renal function in patients receiving extracorporeal shockwave lithotripsy (SWL).
      PATIENTS AND METHODS: This study prospectively recruited 320 patients with
      solitary radiopaque renal stones <15 mm in size. Patients were randomized to
      receive one of four shockwave protocols: (1) standard protocol (no ramping or
      pause); (2) ramping protocol alone; (3) ramping and pause protocols; or (4) pause
      protocol alone. Spot urine samples were collected before and for 2 years after
      treatment to monitor the levels of the renal fibrosis marker procollagen III
      aminoterminal propeptide (PIIINP) by blinded research staffs. Blood pressure and
      serum creatinine levels were also monitored during follow-up. RESULTS: The four
      groups had comparable baseline data and treatment parameters. Significant
      increases (p < 0.05) in the urinary PIIINP levels from 6 weeks until 18 months
      after SWL were observed among all patients and in individual groups. PIIINP
      levels peaked at 1 year after SWL and gradually decreased to the baseline at 2
      years. At the 2-year follow-up point, the overall serum creatinine levels
      remained significantly elevated (76.21-80.01 MUmol/L, p < 0.001). Twenty (9.95%)
      patients developed new-onset hypertension and another 43 (36.4%) experienced
      worsening blood pressure control. However, no differences were observed among the
      four treatment groups. CONCLUSIONS: SWL led to significant increases in renal
      fibrosis marker levels for up to 18 months after treatment. However, no
      differences in changes in renal fibrosis marker and serum creatinine levels and
      worsening of blood pressure control were observed with respect to the use of
      either ramping or pause treatment protocols.

PMID- 29205050
TI  - HRMS for the quantification of xenobiotics in biological samples.

PMID- 29205051
TI  - Quantitative analysis of imetelstat in plasma with LC-MS/MS using solid-phase or
      hybridization extraction.
AB  - AIM: Imetelstat, a 13-mer oligonucleotide with a lipid tail is being evaluated
      for treating hematologic myeloid malignancies. This report describes the
      development of extraction and quantification methods for imetelstat. Methodology
      & results: Imetelstat was extracted using SPE (rat plasma) or by hybridization
      using a biotinylated capture probe (human plasma) and was quantified by LC-MS/MS.
      Calibration curves were established (0.1-50 MUg/ml). Stability of imetelstat in
      plasma was demonstrated. Concentrations of imetelstat extracted using either of
      the methods and quantified with LC-MS/MS were comparable with a validated ELISA.
      CONCLUSION: Two extraction methods (solid phase and hybridization) were developed
      for quantifying imetelstat in plasma using LC-MS/MS. The hybridization extraction
      in combination with LC-MS/MS is a novel extraction approach.

PMID- 29205052
TI  - Microspray and microflow liquid chromatography: the way forward for LC-MS
      bioanalysis.

PMID- 29205053
TI  - 2017 White Paper: rise of hybrid LBA/LCMS immunogenicity assays (Part 2: hybrid
      LBA/LCMS biotherapeutics, biomarkers & immunogenicity assays and regulatory
      agencies' inputs).
AB  - The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in
      Los Angeles/Universal City, California on 3-7 April 2017 with participation of
      close to 750 professionals from pharmaceutical/biopharmaceutical companies,
      biotechnology companies, contract research organizations and regulatory agencies
      worldwide. WRIB was once again a 5-day, weeklong event - a full immersion week of
      bioanalysis, biomarkers and immunogenicity. As usual, it was specifically
      designed to facilitate sharing, reviewing, discussing and agreeing on approaches
      to address the most current issues of interest including both small and large
      molecule analysis involving LCMS, hybrid ligand binding assay (LBA)/LCMS and LBA
      approaches. This 2017 White Paper encompasses recommendations emerging from the
      extensive discussions held during the workshop, and is aimed to provide the
      bioanalytical community with key information and practical solutions on topics
      and issues addressed, in an effort to enable advances in scientific excellence,
      improved quality and better regulatory compliance. Due to its length, the 2017
      edition of this comprehensive White Paper has been divided into three parts for
      editorial reasons. This publication (Part 2) covers the recommendations for
      biotherapeutics, biomarkers and immunogenicity assays using hybrid LBA/LCMS and
      regulatory agencies' inputs. Part 1 (LCMS for small molecules, peptides and small
      molecule biomarkers) and Part 3 (LBA: immunogenicity, biomarkers and
      pharmacokinetic assays) are published in Volume 9 of Bioanalysis, issues 22 and
      24 (2017), respectively.

PMID- 29205054
TI  - Best practices protocol for the evaluation of bulbar dysfunction: summary
      recommendations from the NEALS bulbar subcommittee symposium.
AB  - OBJECTIVE: The aim of this Symposium was to develop a consensus based, bulbar
      assessment protocol for implementation within NEALS clinics. METHODS: A one-day
      symposium, held in April 2017, was organized into Speech and Swallowing sections
      to establish summary recommendations for the assessment of bulbar dysfunction
      within each group. RESULTS: Summary recommendations included speech referrals and
      AAC evaluations at initial visit, CNS-BFS, maximum sustained phonation, and
      speaking rate. Dysarthria evaluation included the speech subsystem involvement of
      respiration, phonation, resonance, and articulation. Specific recommendations for
      swallowing were established for each of the following domains: dietary/oral
      intake, airway defense physiologic capacity, swallow safety screen, patient
      reported swallow-related outcomes, oral sensorimotor exam, and pulmonary
      function. Practice parameters focused upon patient education and unresolved
      questions included the use of videofluoscopy, monitoring diet progression, and
      swallow safety screening. CONCLUSIONS: The working goal is to establish a
      clinical bulbar protocol, designed to be incorporated within ALS clinics and
      ultimately to formulate a best practice set of bulbar ALS guidelines, available
      for implementation throughout the international ALS community.

PMID- 29205055
TI  - Determination of olopatadine in human tears by hydrophilic interaction liquid
      chromatography-MS/MS method.
AB  - AIM: The objective of the study was development of hydrophilic interaction liquid
      chromatography-ESI/MS/MS method for the determination of olopatadine in tear
      matrix. MATERIALS & METHODS: Separation was performed on Acquity BEH amide column
      (2.1 * 100 mm, 1.7 MUm). The mobile phase was consisted of 0.1% formic acid in
      water and acetonitrile. Mianserin hydrochloride was implemented as an internal
      standard. The artificial tear fluid was used as matrix. The tear samples were
      collected using Schirmer test strips. For the optimization of ultra pressure
      liquid chromatography conditions, Box-Benhken design was utilized. RESULTS: The
      optimal values of the ion source and collision cell parameters were found.
      Quantification was performed in multiple reaction monitoring mode. The optimized
      method was fully validated. CONCLUSION: The proposed method was utilized for
      monitoring of olopatadine in human tear.

PMID- 29205056
TI  - Ocular bioanalysis: challenges and advancements in recent years for these rare
      matrices.
AB  - There are many ocular diseases still presenting unmet medical needs. Therefore,
      new ophthalmologic drugs are being developed. Bioanalysis of eye compartments
      (along with plasma and other tissues) is important to determine exposure of the
      target organ to the drug and to help interpret local pharmacological or toxic
      effects. This review article identifies several challenges that occur within
      ocular bioanalysis. They include sample collection and preparation, analytical
      issues, sourcing control matrix, data interpretation and regulatory requirements.
      It summarizes how these challenges have been recently addressed, how research has
      advanced and which questions remain unanswered. Recommendations are made based on
      the literature and our practical experience within ocular bioanalysis and future
      perspectives are discussed.

PMID- 29205057
TI  - Gender differences in inflammatory bowel disease: Explaining body image
      dissatisfaction.
AB  - The aim of this study was to examine the role of body image problems in the
      context of inflammatory bowel disease and to explore gender differences in these
      associations. A sample of inflammatory bowel disease patients (60 males and 140
      females) was collected. Findings from a multi-group analysis show that
      inflammatory bowel disease symptomatology may impact on body image in both male
      and female patients through the effect of body-image-related cognitive fusion.
      Body image difficulties in the context of inflammatory bowel disease should not
      be a neglected dimension in research aiming at understanding the psychosocial
      effects of inflammatory bowel disease and by health professionals working with
      these patients.

PMID- 29205058
TI  - Towards a critical epidemiology approach for applied sexual health research.
AB  - Critical approaches may benefit epidemiological studies of sexual health. This
      article proposes a critical approach, reconcilable with social epidemiological
      enquiry. Key aims of critical epidemiology for sexual health are identified, from
      which three criticisms of practice emerge: (1) lack of attention to socio
      cultural contexts, (2) construction of 'risk' as residing in the individual and
      (3) enactment of public health agendas which privilege and pathologise certain
      behaviours. These reflect and construct an apolitical understanding of population
      health. This article proposes features of a critical epidemiology that represent
      a morally driven re-envisioning of the focus, analysis and interpretation of
      epidemiological studies of sexual health.

PMID- 29205059
TI  - 5TR1 aptamer-PEGylated liposomal doxorubicin enhances cellular uptake and
      suppresses tumour growth by targeting MUC1 on the surface of cancer cells.
AB  - Employing targeting ligands with high affinity to tumour receptors is an
      important strategy to increase treatment efficacy. The use of aptamers as
      targeting agent is increasingly prevalent in drug delivery systems. Mucin1 (MUC1)
      is a glycoprotein that is over-expressed on the surface of several cancer cells
      and plays an important role in metastasis and invasion. 5TR1-aptamer is a DNA
      aptamer, which targets MUC1 receptors. The present study investigated the anti
      tumour activity and therapeutic effectiveness of 5TR1-aptamer-PEGylated liposomal
      doxorubicin (PLD) delivery system in C26 tumour-bearing mice. The in vitro
      experiments demonstrated enhanced cytotoxicity and cellular uptake of PLD at the
      presence of 5TR1 aptamer into MUC1+C26 cell line. Biodistribution study indicated
      that aptamer conjugation increased tumour accumulation of PLDs. Pharmacokinetic
      analysis showed despite higher clearance rate, selective delivery of doxorubicin
      to tumour tissue was increased in the 5TR1-Doxil group. In C26-bearing tumour
      mice, treatment with 5TR1-Doxil exhibited significant deceleration in tumour
      growth and enhanced survival. The results suggested that 5TR1 aptamer is
      promising ligand for active targeting which improves therapeutic efficiency of
      PLD in cancer therapy.

PMID- 29205060
TI  - Correction to: Nematollahi et al., Ternary complex of plasmid DNA with NLS-Mu-Mu
      protein and cationic niosome for biocompatible and efficient gene delivery: a
      comparative study with protamine and lipofectamine.

PMID- 29205061
TI  - Does Advancing Technology Improve Outcomes? Comparison of the Da Vinci
      Standard/S/Si to the Xi Robotic Platforms During Robotic Nephroureterectomy.
AB  - INTRODUCTION: With the introduction of laparoscopy and now robotics, more
      patients are able to reap benefit from minimally invasive techniques during
      urologic surgery. With these advancing technologies, it is important to evaluate
      whether the outlay of hospital capital actually improves patient care. To date,
      there has been little literature regarding the impact of these advances on
      patient outcomes. In this article, we directly compare perioperative outcomes and
      hospital costs between the older da Vinci Standard/S/Si platform and the newer Xi
      robotic platform during nephroureterectomy. METHODS: A review of our robotic
      nephroureterectomy database between April 2009 and December 2017 identified 87
      patients, 30 in group 1 (Xi) and 57 in group 2 (Standard/S/Si). Preoperative,
      perioperative, and postoperative parameters as well as hospital costs were
      evaluated. Independent t-test was performed for continuous variables, while
      categorical variables were evaluated using chi-square tests or Fisher's exact
      test. RESULTS: There were no significant differences between groups
      preoperatively. Operative time using the Xi was shorter, 184.4 vs 232.09 minutes
      (p = 0.0035). Other perioperative variables were similar. There was more
      lymphovascular invasion in group 2 (p = 0.0108), but there were higher stage
      tumors in group 1 (p < 0.0001). More patients underwent lymph node dissection in
      group 1 (p = 0.0186). Complications were similar between groups. Costs for
      anesthesia were less in group 1, which led to decreased total hospitalization
      costs (p < 0.001) Conclusion: Operative times were found to be less with the
      daVinci Xi, without any other significant difference in patient outcomes between
      the groups. Anesthesia and operating room cost were substantial factors in
      lowering the overall hospital costs. More multi-institutional studies with larger
      groups of patients are needed to determine if advancing technology really
      improves outcomes.

PMID- 29205062
TI  - MicroRNA-150 protects against cigarette smoke-induced lung inflammation and
      airway epithelial cell apoptosis through repressing p53: MicroRNA-150 in CS
      induced lung inflammation.
AB  - Cigarette smoke (CS) exposure is an important risk factor for chronic obstructive
      pulmonary disease (COPD). MicroRNA-150 (miR-150) is involved in several
      inflammatory diseases. However, little is known about the role of miR-150 in the
      pathogenesis of COPD. In this study, we established a CS-related mouse model of
      COPD and evaluated the impact of miR-150 on CS-induced lung inflammation. We
      further investigated the effects of miR-150 overexpression on pro-inflammatory
      cytokine production and apoptosis in airway epithelial cells exposed to CS
      extract (CSE). It was found that miR-150 was significantly ( p < 0.05)
      downregulated in the lungs of CS-exposed mice, compared to control mice under
      normal air. The CSE-exposed BEAS-2B airway epithelial cells displayed a four- to
      six-fold reduction in miR-150 levels, compared to control cells ( p < 0.05).
      Delivery of miR-150 mimic attenuated CS-induced lung inflammation and
      accumulation of neutrophils, lymphocytes, and macrophages in bronchoalveolar
      lavage fluid. Moreover, miR-150 overexpression prevented the induction of
      interleukin-6, tumor necrosis factor alpha, and interleukin-8 expression and
      nuclear factor kappa B (NF-kappaB) transcriptional activity in BEAS-2B cells by
      CSE. Additionally, miR-150 protected BEAS-2B cells from CSE-induced apoptosis,
      which was associated with reduced p53 expression. Co-expression of p53 restored
      apoptotic response to CSE in miR-150-overexpressing BEAS-2B cells. Collectively,
      miR-150 suppresses CS-induced lung inflammation and airway epithelial cell
      apoptosis, which is causally linked to repression of p53 expression and NF-kappaB
      activity. Restoration of miR-150 expression may represent a potential therapeutic
      strategy for CS-related COPD.

PMID- 29205063
TI  - How should health leaders approach morally contentious policy issues?
AB  - In terms of their expertise, experience, and impact on patient care, health
      leaders occupy an important position in our health system. These leaders are
      expected to provide value to their constituents, and this value is connected to
      moral objectives that are fundamental to the delivery of healthcare. In some
      cases, leaders may interpret a certain politico-medical decision, policy, or
      directive to interfere with these moral objectives. In these instances, leaders
      can either expressly object to a decision or sideline moral views while enacting
      these policies or directives. We present several contemporary examples of these
      issues as well as the experiences of health leaders. Subsequently, we review
      relevant sections of the Canadian College of Health Leaders' Code of Ethics to
      identify existing guidance. Ultimately, we conclude that more work is needed to
      define the role of leaders in these circumstances, as well as the limitations of
      any resistance.

PMID- 29205065
TI  - ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS
      Screen.
AB  - BACKGROUND: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a short
      assessment by which neuropsychological symptoms can be detected and quantified in
      people with ALS. To avoid potential practice effects with repeated
      administration, here we present alternative versions of the ECAS suitable for
      measuring change over time. OBJECTIVE: To develop two alternate versions of the
      ECAS: ECAS-B and ECAS-C. METHOD: One hundred and forty-nine healthy adult
      participants were recruited. Thirty participants completed a pilot study in
      developing the alternate versions. Two groups of 40 participants were
      administered the ECAS-B or ECAS-C and compared to published data of the original
      ECAS (ECAS-A) to determine equivalence. An additional 39 participants were
      administered the ECAS consecutively, either repeating the original version (ECAS
      A-A-A) serially or the different versions (ECAS-A-B-C) to determine potential
      practice effects. Recordings of assessments were scored by a second researcher to
      determine inter-rater reliability. RESULTS: No significant differences were found
      between versions (A, B, C) of the composite performance measures of ALS Specific,
      ALS Non-Specific, and ECAS Total scores. Repeated serial administration of ECAS-A
      (A-A-A) produced some practice effects for composite scores, whereas no such
      effects were found when alternate versions were administered serially (A-B-C).
      Exceptionally high intra-class correlations were found for all three versions of
      the ECAS suggesting a high degree of rater agreement. CONCLUSION: The newly
      developed alternate forms of the ECAS are both highly equitable to the original
      ECAS-A and enable avoidance of practice effects, thus supporting their use in
      measuring cognition and behaviour over time.

PMID- 29205066
TI  - An analysis of barriers to entry of cardiac rehabilitation in patients with
      diabetes: Using data from the National Audit of Cardiac Rehabilitation.
AB  - BACKGROUND: UK cardiac rehabilitation has reached for the first time 50% uptake
      in 2016; however, this still leaves 50% of the eligible group not starting
      cardiac rehabilitation. The characteristics of patients missing cardiac
      rehabilitation are relatively unknown with some studies in America suggesting
      that patients with diabetes have a reduced likelihood of joining cardiac
      rehabilitation. METHODS: This study used routinely collected data from the
      National Audit of Cardiac Rehabilitation to investigate proportional differences
      in patients with cardiovascular disease with, and without, diabetes taking up the
      offer of cardiac rehabilitation. RESULTS: The proportion of patients with
      diabetes entering cardiac rehabilitation dropped by between 7% and 15% depending
      on the age group (<40 years, 7% reduction; 61-80 years, 15%). The study's results
      showed that in all demographic and diagnostic groups, the proportion of patients
      with diabetes was significantly less than that of the eligible group ( p <
      0.001). There was no difference in the proportion of loss, from eligible to
      starting cardiac rehabilitation, between males and females, which was 13% for
      both groups. CONCLUSION: This study confirms, in a new UK population with over
      121,002 eligible patients, that there is a statistically significant drop in
      patients with diabetes taking up cardiac rehabilitation. This study is unique in
      looking at all four key diagnosis and treatment groups and comparing them to
      those taking up cardiac rehabilitation. To achieve the target of 65% uptake set
      by NHS England, improvements in identifying and targeting complex patients, such
      as those with diabetes, need to be adopted.

PMID- 29205064
TI  - 2017 White Paper on recent issues in bioanalysis: a global perspective on
      immunogenicity guidelines & biomarker assay performance (Part 3 - LBA:
      immunogenicity, biomarkers and PK assays).
AB  - The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los
      Angeles/Universal City, California, on 3-7 April 2017 with participation of close
      to 750 professionals from pharmaceutical/biopharmaceutical companies,
      biotechnology companies, contract research organizations and regulatory agencies
      worldwide. WRIB was once again a 5-day, week-long event - a full immersion week
      of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically
      designed to facilitate sharing, reviewing, discussing and agreeing on approaches
      to address the most current issues of interest including both small- and large
      molecule analysis involving LC-MS, hybrid ligand-binding assay (LBA)/LC-MS and
      LBA approaches. This 2017 White Paper encompasses recommendations emerging from
      the extensive discussions held during the workshop, and is aimed to provide the
      bioanalytical community with key information and practical solutions on topics
      and issues addressed, in an effort to enable advances in scientific excellence,
      improved quality and better regulatory compliance. Due to its length, the 2017
      edition of this comprehensive White Paper has been divided into three parts for
      editorial reasons. This publication (Part 3) covers the recommendations for large
      molecule bioanalysis, biomarkers and immunogenicity using LBA. Part 1 (LC-MS for
      small molecules, peptides and small molecule biomarkers) and Part 2 (hybrid
      LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) are published in
      volume 9 of Bioanalysis, issues 22 and 23 (2017), respectively.

PMID- 29205067
TI  - A Message from the Guest Editor.

PMID- 29205068
TI  - Evaluation of the role of incentive structure on student participation and
      performance in active learning strategies: A comparison of case-based and team
      based learning.
AB  - BACKGROUND: Student participation is important for the success of active learning
      strategies, but participation is often linked to the level of preparation. At our
      institution, we use two types of active learning activities, a modified case
      based learning exercise called active learning groups (ALG) and team-based
      learning (TBL). These strategies have different assessment and incentive
      structures for participation. Non-cognitive skills are assessed in ALG using a
      subjective five-point Likert scale. In TBL, assessment of individual student
      preparation is based on a multiple choice quiz conducted at the beginning of each
      session. METHODS: We studied first-year medical student participation and
      performance in ALG and TBL as well as performance on course final examinations.
      RESULTS: Student performance in TBL, but not in ALG, was strongly correlated with
      final examination scores. Additionally, in students who performed in the upper
      33rd percentile on the final examination, there was a positive correlation
      between final examination performance and participation in TBL and ALG. This
      correlation was not seen in students who performed in the lower 33rd percentile
      on the final examinations. CONCLUSIONS: Our results suggest that assessments of
      medical knowledge during active learning exercises could supplement non-cognitive
      assessments and could be good predictors of performance on summative
      examinations.

PMID- 29205069
TI  - Dried blood spots in therapeutic drug monitoring and toxicology.

PMID- 29205070
TI  - Trends in types of calls managed by U.S. poison centers 2000-2015.
AB  - AIM: The number of cases reported to poison centers has decreased since 2008 but
      there is evidence that the complexity of calls is increasing. OBJECTIVES: The
      objectives are to evaluate national poison center data for trends in reason and
      how these changes effect management site, medical outcomes, and poison center
      workload. METHODS: Data regarding reason, age, management site, and medical
      outcome were extracted from annual reports of the National Poison Data System
      from 2000 to 2015. The proportion of cases by year were determined for
      unintentional and intentional exposures. Analysis of data from a single poison
      center from 2005 to 2015 compared the number of interactions between poison
      center staff and callers for unintentional versus intentional reasons. RESULTS:
      Trend analyses found that from 2000 to 2015 the percent of unintentional cases
      decreased (from 85.9 to 78.4%, p < .0001) and the percent of intentional cases
      increased (from 11.3 to 17.6%, p < .0001). Age distribution changed with a
      decrease in children <13 years of age and increase in adolescents and adults. In
      these latter two age groups, the proportion due to intentional exposure increased
      while unintentional declined. The distribution of management sites changed over
      the 16-year period, with a decrease in non-HCF cases and significant increase in
      percent of cases treated in a HCF. The frequencies of moderate effect, major
      effect, and death were significantly higher for intentional exposures than for
      unintentional exposures. Analysis of data entry notes from a single center showed
      that the mean number of notes per unintentional case (1.61 +/- 0.08) was
      significantly different from the mean number of notes per intentional case (9.23
      +/- 0.68) (p < .0001). DISCUSSION: Poison centers are managing more intentional
      exposures and fewer unintentional exposures. Intentional exposures require more
      poison center staff expertise and time. CONCLUSION: Looking only at poison center
      total call volume may not be an adequate method to gauge productivity.

PMID- 29205071
TI  - Impact of helmet use in equestrian-related traumatic brain injury: a matched
      pairs analysis.
AB  - PURPOSE: Traumatic brain injury is an important health concern in equestrian
      sports. Nevertheless, the use of safety helmets, especially in recreational
      riding, is reported to be rare. The purpose of this study was to perform the
      first matched-pairs analysis of traumatic brain injury with regard to the use of
      helmets. MATERIALS AND METHODS: In a multicenter retrospective database analysis
      40 patients (mean age: 35 +/- 17.13 years; 34 female & 6 male) were combined in
      20 matched pairs based on age group, gender and trauma mechanism. Admission
      trauma computed tomography was qualitatively analyzed for the presence or absence
      of fractures or intracranial hemorrhage. Quantitatively, in patients with
      intracranial hemorrhage dedicated volumetry of the blood volume was performed.
      Odds ratio and relative risk were calculated for the endpoints fractures and
      intracranial hemorrhage. Crude risk ratio and lesion volume differences between
      helmeted and unhelmeted riders were compared. RESULTS: Concerning skull
      fractures, in this cohort 6 patients (85.7% of all patients with fractures) did
      not wear a helmet and only one (14.3%) wore a helmet (p = .068).and fractures
      were considered more complex in the unhelmeted subgroup. Intracranial hemorrhage
      occurred significantly more often in the unhelmeted subgroup (10 vs. 2; p =
      .008). Moreover, the total lesion volume with 19.31 +/- 23.93ml in the unhelmeted
      subgroup, presenting with intracranial hemorrhage, was significantly higher than
      in the control group (0.65 +/- 0.35ml; p = .002). Odds ratios were 9 for
      intracranial hemorrhage (p = .014) and 8.14 for skull fractures without helmet (p
      = .09). Altogether, the relative risk for intracranial bleeding for unhelmeted
      riders was 5-fold higher and the relative risk reduction was 96% by wearing a
      safety helmet. CONCLUSIONS: Under consideration of comparable trauma mechanisms,
      horseback riders that do not wear a safety helmet are at risk to suffer
      significantly more severe brain injury than helmeted riders. Therefore, safety
      helmets are recommendable for all horseback riders.

PMID- 29205072
TI  - Enamel matrix proteins regulate hypoxia-induced cellular biobehavior and
      osteogenic differentiation in human periodontal ligament cells.
AB  - Hypoxia is a crucial microenvironment for inflamed periodontal tissue and
      periodontal wound healing. Enamel matrix proteins (EMPs) potentially can promote
      the formation of new periodontium. The effects of EMPs on periodontal ligament
      cells under hypoxia, however, remain unclear. We investigated the effects of EMPs
      on cellular biobehavior and osteogenic differentiation of human periodontal
      ligament cells (hPDLCs) under hypoxia. Under cobalt chloride (CoCl2)-induced
      hypoxia, cellular biobehavior of hPDLCs, including proliferation, attachment,
      spreading, and migration with or without EMPs, was evaluated by 3-(4, 5
      dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), cell counting,
      spreading area measurement and wound scratch assay. The osteogenic activity of
      hPDLCs was assessed using alkaline phosphatase (ALP) and alizarin red S staining
      (ARS). The expressions of osteogenic genes including runt related transcription
      factor 2 (Runx2), ALP, osteocalcin (OCN) and collagen type I (Col-I) were
      detected using real time quantitative PCR, western blot and immunocytochemistry
      assays. The biobehavior and osteogenic differentiation of hPDLCs were inhibited
      significantly under hypoxia. EMPs have no effect on cell proliferation under
      mimicked hypoxia. EMPs partly reversed the inhibitory effects of hypoxia,
      however, for other cellular biobehavior including attachment, spreading and
      migration, and markedly up-regulated osteogenic differentiation activities
      including ALP, mineralization ability and the expressions of osteogenic genes
      such as Runx2, ALP, osteocalcin, and collagen type I in hPDLCs under hypoxia.
      EMPs attenuate the hypoxic injury to cellular biobehavior and osteogenic
      differentiation in hPDLCs under hypoxia.

PMID- 29205073
TI  - Effects of citronella oil (Cymbopogon winterianus Jowitt ex Bor) on Spodoptera
      frugiperda (J. E. Smith) midgut and fat body.
AB  - The armyworm, Spodoptera frugiperda, is the principal pest of corn in Brazil.
      Control is achieved primarily by synthetic insecticides, which cause problems for
      the agro-ecosystem. Alternative methods of control are under investigation and
      citronella (Cymbopogon winterianus) essential oil appears to be a promising
      agent. We investigated the effects of citronella oil using histological,
      histochemical and immunohistochemical methods. The midgut of larvae treated with
      citronella exhibited altered epithelium including cytoplasmic protrusions,
      columnar cell extrusion, pyknotic nuclei, and increased periodic acid-Schiff
      positive granules. Regenerative cells in the epithelium of the midgut increased
      in number, which facilitated subsequent regeneration of this tissue. After
      exposure to citronella, trophocytes, the principal cell type of the fat body,
      possessed enlarged vacuoles and mitotic bodies, and contained reduced amounts of
      glycogen, lipid, and protein. Citronella oil caused morphological changes of the
      midgut and reduction of stored resources in the fat body, which may adversely
      affect insect reproduction and survival.

PMID- 29205074
TI  - Overweight and obesity risk factors in children aged 3-7 years: a prospective
      study in the city of Krakow.
AB  - BACKGROUND: Early identified factors determining overweight and obesity in
      childhood may be important for preventive purposes. AIM: To evaluate the
      influence of the commonly accepted and hypothetical risk factors for
      overweight/obesity and their mutual relations, using the method of classification
      trees. SUBJECTS AND METHODS: The data were collected during anthropometric
      surveys carried out in 2010 in Krakow, Poland. The study involved 1042 pre-school
      children aged 3-7 years. BMI was calculated for all subjects classified as
      underweight, normal body weight and overweight, according to the IOTF cut-offs.
      In order to determine the correlation between genetic, environmental and
      lifestyle factors and the child's BMI, this study used information from a
      questionnaire filled in by the mothers. RESULTS: Relatively high birth weights,
      relatively long times of breastfeeding and father's obesity were conducive to the
      appearance of overweight and obesity in boys. Other overweight risk factors
      included alcohol consumption by the mother, her low education level and a
      relatively low mother's age at birth. Among girls, factors leading to overweight
      included high birth weight, high father's BMI and family situation reported as
      below very good by their mothers. It was found that a moderate duration of
      breastfeeding is conducive to a normal weight of children at pre-school age,
      although in boys this regularity is better documented. CONCLUSIONS: The
      biological, social and lifestyle factors related to the child's mother
      significantly determined the child's BMI.

PMID- 29205075
TI  - The Nick Norgan Award 2017.

PMID- 29205076
TI  - Connecting science and practice: Focus and directions for the next 10 years.

PMID- 29205077
TI  - Forty years of landmark trials undertaken by the Danish Breast Cancer Cooperative
      Group (DBCG) nationwide or in international collaboration.
AB  - BACKGROUND: Over the past 40 years the Danish Breast Cancer Cooperative Group
      (DBCG) has made significant contributions to improve outcome and to make
      treatment of patients with early breast cancer more tolerable through nationwide
      and international trials evaluating loco-regional and systemic treatments. These
      trials have been instrumental to establish standards for the treatment of early
      breast cancer. METHODS: The DBCG 82 trials had a global impact by documenting
      that the significant gain in loco-regional recurrence from postmastectomy
      radiation added to systemic therapy was associated with a reduction in distant
      recurrence and mortality in high-risk pre- and postmenopausal patients. The DBCG
      trials comparing breast conserving surgery and radiotherapy with mastectomy and
      more recently the trial of internal mammary node irradiation also had a major
      impact of practice. The trials initiated by the DBCG 40 years ago on tamoxifen
      and cyclophosphamide based chemotherapy became instrumental for the development
      of adjuvant systemic therapy not only due to their positive results but by
      sharing these important data with other members of the Early Breast Cancer
      Trialist' Collaborative Group (EBCTCG). Trials from the DBCG have also been
      important for highlighting the relative importance of anthracyclines and taxanes
      in the adjuvant setting. Furthermore, DBCG has made a major contribution to the
      development of aromatase inhibitors and targeted adjuvant treatment for human
      epidermal growth factor receptor 2 positive breast cancers. RESULTS: The
      substantial impact of these treatment improvements is illustrated by a 46.7% 10
      year overall survival of early breast cancer patients treated in 1978-1987
      compared to 71.5% for patients treated 2008-2012. CONCLUSIONS: The trials
      conducted and implemented by the DBCG appear to have a major impact on the
      substantial survival improvements in breast cancer.

PMID- 29205078
TI  - An oral pharyngeal scope for objective oropharyngeal examination: a new device
      for oropharyngeal study.
AB  - OBJECTIVE: There has been little progress in examination of the oropharynx with a
      light source such as electric light, a penlight, or a forehead mirror over the
      past 100 years. It is therefore necessary to develop methods to display and
      record oropharyngeal observations. METHOD: Since the aim of this study was to
      assess the safeness to use from the perspective of physicians, medical staffs,
      patients, and patients' families and usefulness of pharyngeal scope, the number
      of devices was limited, the number of patients was not set based on hypothetical
      statistical tests. RESULTS: A total of 150 volunteers were enrolled in this
      study. Among them, 96 underwent examination alone and the remaining 28 underwent
      treatment procedures. The study was done without any complications in all 150
      cases. Most (91.3%) physicians hoped to continue using the new device if
      available. When comparing the use of the device for observation alone and for
      treatment procedures, there was no significant difference for evaluation items (p
      > .05) except convenience factor which received a significantly different (p =
      .0154) evaluation from physicians for observation alone and for treatment
      procedures. A positive evaluation was received about examination,
      recording/display and explanation from the patients and patients' families.
      CONCLUSIONS: Our new device received positive evaluations by who underwent
      examination of the oral cavity and pharynx, recording of the results, and
      treatment procedures.

PMID- 29205079
TI  - Combination antibiotic therapy for Pseudomonas aeruginosa bacteremia in febrile
      neutropenic patients? The question still remains.

PMID- 29205080
TI  - The potential benefits from respiratory gating for breast cancer patients
      regarding target coverage and dose to organs at risk when applying strict dose
      limits to the heart: results from the DBCG HYPO trial.
AB  - PURPOSE: The potential benefits from respiratory gating (RG) compared to free
      breathing (FB) regarding target coverage and dose to organs at risk for breast
      cancer patients receiving post-operative radiotherapy (RT) in the DBCG HYPO
      multicentre trial are reported. MATERIAL AND METHODS: Patients included in the
      DBCG HYPO trial were randomized between 50 Gy in 25 fractions (normofractionated)
      versus 40 Gy in 15 fractions (hypofractionated). A tangential forward field-in
      field dose planning technique was used to cover the clinical target volume (CTV)
      with the intent to limit dose to the left anterior descending coronary artery
      (LADCA) to 20 Gy and 17 Gy in the normo- and hypofractionated arms, respectively.
      Treatment plan data for 1327 patients from four Danish centres was
      retrospectively analyzed. FB right-sided patients served as control group for the
      left-sided patients regarding CTV V95% (relative volume receiving at least 95% of
      the prescribed dose), mean heart dose (MHD) and mean lung dose (MLD). RESULTS:
      Median CTV V95% was for FB right-sided, FB left-sided and RG left-sided patients
      94.6, 92.6 and 94.7% for normofractionated therapy, respectively, and 94.6, 91.8
      and 94.4% for hypofractionated therapy and did not differ significantly for RG
      left-sided plans compared to FB right-sided in either study arm. CTV V95% was
      significantly lower for FB versus RG for left-sided plans in both arms. Median
      MHD was 0.7, 1.8 and 1.5 Gy (normofractionated therapy) versus 0.6, 1.5 and 1.2
      Gy (hypofractionated therapy), respectively. The corresponding median MLD was
      9.0, 8.3 and 7.3 Gy versus 7.3, 6.4 and 5.8 Gy, respectively. CONCLUSIONS: RG for
      left-sided breast cancer patients ensured similar CTV V95% as for FB right-sided
      patients. MLD was lower for RG due to the increased lung volume. MHD was
      generally low due to strict protocol-defined maximum dose to LADCA, but for left
      sided patients RG led to significantly lower MHD.

PMID- 29205082
TI  - Energetic Modalities as a Self-Care Technique to Reduce Stress in Nursing
      Students.
AB  - This article describes the outcomes of nursing students taking a course in
      complementary and alternative therapies focusing on energetic modalities that
      were used as a means of self-care. Students kept journal logs and did a formal
      presentation for the class. Nursing students reported decreased stress and
      improved concentration, academic performance, productivity, and problem-solving
      while experiencing a greater appreciation of their clinical experiences. Using
      Therapeutic Touch and other subtle energy interactions, the students also cited
      improved interpersonal relationships, increased feelings of calmness, a higher
      degree of self-awareness and self-care, reduced physical pain, increased energy,
      and greater appreciation of the world around them. The theoretical framework was
      Margret Neuman's theory of health as expanding consciousness. While this is an
      elective nursing course, the nursing students were primarily juniors and seniors
      already taking clinical courses. A research study with a wide sample of student
      participants, especially freshmen, and using quantitative as well as qualitative
      measures would be beneficial to determine if such a course should be part of the
      standard nursing curriculum to not only expand nurses' understanding of
      complementary and alternative therapies but also to help students with their own
      self-care and influence their practice as clinicians.

PMID- 29205081
TI  - Uncovering mechanisms of nuclear degradation in keratinocytes: A paradigm for
      nuclear degradation in other tissues.
AB  - Eukaryotic nuclei are essential organelles, storing the majority of the cellular
      DNA, comprising the site of most DNA and RNA synthesis, controlling gene
      expression and therefore regulating cellular function. The majority of mammalian
      cells retain their nucleus throughout their lifetime, however, in three mammalian
      tissues the nucleus is entirely removed and its removal is essential for cell
      function. Lens fibre cells, erythroblasts and epidermal keratinocytes all lose
      their nucleus in the terminal differentiation pathways of these cell types.
      However, relatively little is known about the pathways that lead to complete
      nuclear removal and about how these pathways are regulated. In this review, we
      aim to discuss the current understanding of nuclear removal mechanisms in these
      three cell types and expand upon how recent studies into nuclear degradation in
      keratinocytes, an easily accessible experimental model, could contribute to a
      wider understanding of these molecular mechanisms in both health and pathology.

PMID- 29205083
TI  - A multifactorial investigation of captive gorillas' intraspecific gestural
      laterality.
AB  - Multifactorial investigations of intraspecific laterality of primates' gestural
      communication aim to shed light on factors that underlie the evolutionary origins
      of human handedness and language. This study assesses gorillas' intraspecific
      gestural laterality considering the effect of various factors related to gestural
      characteristics, interactional context and sociodemographic characteristics of
      signaller and recipient. Our question was: which factors influence gorillas'
      gestural laterality? We studied laterality in three captive groups of gorillas (N
      = 35) focusing on their most frequent gesture types (N = 16). We show that
      signallers used predominantly their hand ipsilateral to the recipient for tactile
      and visual gestures, whatever the emotional context, gesture duration,
      recipient's sex or the kin relationship between both interactants, and whether or
      not a communication tool was used. Signallers' contralateral hand was not
      preferentially used in any situation. Signallers' right-hand use was more
      pronounced in negative contexts, in short gestures, when signallers were females
      and its use increased with age. Our findings showed that gorillas' gestural
      laterality could be influenced by different types of social pressures thus
      supporting the theory of the evolution of laterality at the population level. Our
      study also evidenced that some particular gesture categories are better markers
      than others of the left-hemisphere language specialization.

PMID- 29205084
TI  - Relationship between cognitive function and balance in a community-dwelling
      population in Japan.
AB  - BACKGROUND: There has been no treatment found yet that cure dementia. Hence it is
      important to establish the evaluation index of cognitive decline before becoming
      dementia. OBJECTIVE: The purpose of this study was to clarify the effective
      balance test indicating early cognitive decline by gender. METHODS: A total of
      218 volunteers (60 years of age and above) who participated in the Iwaki
      promotion health project in 2015 were recruited. We performed three balance
      tests: one leg standing test, functional reach test and static posturography, and
      we used mini-mental state examination (MMSE) to investigate cognitive function.
      RESULTS: As a result of analysis of covariance, there was a statistically
      significant trend in only men that the more the MMSE score declined, the longer
      became the path length with both eyes opened and closed. In the result of
      multiple regression analysis, there was a significant negative association with
      MMSE score and path length with eyes opened or closed in men. There was no
      significant association with MMSE scores and balance tests in women. CONCLUSION:
      The study suggests that static posturography might be a useful balance test to
      assess early cognitive decline in men.

PMID- 29205085
TI  - Incidence and survival of sinonasal adenocarcinoma by site and histologic
      subtype.
AB  - OBJECTIVE: To determine the incidence and survival of sinonasal adenocarcinoma
      (SNAC) by subsite and histologic subtype. STUDY DESIGN: Retrospective database
      review. METHODS: Using the SEER database, we performed a retrospective analysis,
      identified cases of SNAC diagnosed between 1973 and 2013 and analyzed
      demographic, histopathology, clinicopathology, and determinants of disease
      specific survival (DSS). RESULTS: A total of 746 patients with SNAC were
      identified. Median age at diagnosis was 64 years. Overall incidence was 0.44 per
      million, and was higher among blacks (O.R.:1.10-2.07:1) and males (O.R.:1.38
      2.06:1). Nasal cavity (41.5%) was the most common site, followed by maxillary
      (26.5%), and ethmoid (17.4%) sinuses. Intestinal-type adenocarcinoma was less
      likely than Adenocarcinoma not otherwise specified (ANOS) to be found in the
      maxillary sinus (8.8% vs. 30.6%, p < .05). Surgery alone (48.56%) was the most
      common treatment modality, followed by surgery and radiotherapy (RT) (32.5%), and
      RT alone (11.6%). DSS at 5, 10, and 20 years were 63.8%, 57.6%, and 47.0%,
      respectively. DSS was higher for nasal cavity SNAC, lower grade, lower stage, and
      those receiving surgery only. CONCLUSIONS: SNAC is more common among men and
      blacks. Incidence has not changed significantly in the past 40 years. Survival
      varies with grade, stage, histology, subsite, and treatment.

PMID- 29205086
TI  - Well-Meaning Dinosaurs: The Most Potent Enemies of Progress Against Aging.

PMID- 29205087
TI  - Why Actionable Statements Are Needed for Measurement Development.
AB  - Clinical guidelines are an avenue to improve patient outcomes based on best
      available clinical evidence. Actionable statements represent the foundation of a
      clinical guideline and form an important bridge to subsequent performance
      measurement efforts.

PMID- 29205088
TI  - Local failure after radical radiotherapy of non-small cell lung cancer in
      relation to the planning FDG-PET/CT.
AB  - OBJECTIVES: Local recurrence (rec) in lung cancer is associated with poor
      survival. This study examined whether the pattern of failure is associated with
      the most PET avid volume in the planning-FDG-PET/CT scan (p-PET/CT). METHODS: 162
      consecutive inoperable NSCLC patients (pts) receiving radiotherapy between
      January 2012 and April 2014 were reviewed. Radiotherapy was delivered in 2
      Gy/fraction (5f/week) to a total dose of 60-66 Gy. Pts were followed with CT
      scans every third month. Patients with local rec as first event were analyzed.
      For the primary tumor (T) the overlap-fraction (OF) between 50% of SUVpeak on p
      PET/CT and the volume of T-rec was calculated: OF = (SUVp50?T-rec)/min(SUVp50, T
      rec). Similarly for the GTV on the p-CT: OF = (GTV?T-rec)/min(GTV, T-rec). OF was
      based on a rigid registration between p-PET/CT and rec-CT with PET guided
      delineation of T- rec. For lymph nodes (LN), the correlation between the location
      of treated-LN and the location of recurrence-LN was evaluated. RESULTS: 67
      patients developed local rec. 51 pts had rec in T-site, 45 pts in LN-site. Due to
      anatomical changes, reliable registration between p-CT and rec-CT was only
      obtained in 26 pts with T-rec. The median OFSUVp50 was 52, 8% [range 26; 100%]
      and the median OFGTV was 80.5% [19.7; 100%]. Eleven pts had higher OFSUVp50 than
      OFGTV. LN-rec predominantly occurred in the station 2R (32%), 4R (46%), 7 (46%)
      and right hilum (36%). Pts with malignant LNs in station 4R or 7 on p-CT had a
      high risk of rec in these stations; 4R (55%) and 7 (83%). CONCLUSIONS: This study
      indicates that the most PET active volume on p-PET-CT is a driver for rec at T
      site. LN-recurrences predominantly appear in station 2R, 4R, 7 and right hilum.
      Additional confirmatory studies regarding lymph node mapping and selective lymph
      node irradiation is needed.

PMID- 29205089
TI  - Altered Bioenergetic Profile in Umbilical Cord and Amniotic Mesenchymal Stem
      Cells from Newborns of Obese Women.
AB  - Nutritional imbalance and metabolic alterations associated with maternal obesity
      during pregnancy predispose offspring to obesity and/or to type 2 diabetes, but
      the mechanisms underlying these effects are still obscure. In this context, we
      evaluated whether the two main energy-producing pathways (glycolysis and
      mitochondrial oxidative phosphorylation) are impaired in obesity during pregnancy
      thus contributing to metabolic intrauterine alterations. Specifically, we studied
      metabolic abnormalities in the intrauterine life of newborns using stem cells
      isolated from amnion and umbilical cord (hA- and hUC-MSCs). We isolated, at
      delivery, neonatal hUC-MSCs from 13 obese (Ob) and 10 normal weight control (Co)
      women (prepregnancy body mass index >30 and <25 kg/m2, respectively) and hA-MSCs
      from a subgroup of 3 Ob and 3 Co women. The hUC-MSC immunophenotype was
      characterized by flow cytometry. The extracellular acidification rate and oxygen
      consumption rate, which are indicators of glycolysis and mitochondrial
      respiration, respectively, were measured using the Seahorse XFe96 analyzer. Basal
      glycolysis (Co: 27.5 +/- 2.9; Ob: 21.3 +/- 2.3 mpH/min) and glycolytic capacity
      (Co: 65.3 +/- 1.2; Ob: 55.0 +/- 0.3 mpH/min) were significantly lower in Ob-hUC
      MSCs versus Co-hUC-MSCs (P < 0.05 and P < 0.0001, respectively). Mitochondrial
      basal respiration (Co: 46.9 +/- 0.7; Ob: 32.6 +/- 0.8 pmol/min), ATP-linked
      respiration (Co: 29.3 +/- 1.9; Ob: 20.1 +/- 0.3 pmol/min), and maximal
      respiration (Co: 75.2 +/- 5.3; Ob: 50.5 +/- 4.1 pmol/min) were significantly (P <
      0.0001) lower in Ob-hUC-MSCs versus Co-hUC-MSCs. Similarly, bioenergetic profiles
      of the subgroup of Ob-hA-MSCs differed from those of Co-hA-MSCs. These results
      demonstrate that the bioenergetic performance of Ob-h-MSCs is lower in basal
      conditions and in conditions of increased energy demand compared with Co-h-MSCs.
      In conclusion, we describe a new mechanism whereby obesity alters intrauterine
      metabolism. This process could concur to predispose offspring to metabolic
      diseases in adult life.

PMID- 29205090
TI  - Rapamycin Exacerbates Cardiovascular Dysfunction after Complete High-Thoracic
      Spinal Cord Injury.
AB  - Autonomic dysreflexia (AD) is a potentially life-threatening syndrome in
      individuals with spinal cord injury (SCI) above the T6 spinal level that is
      characterized by episodic hypertension in response to noxious stimuli below the
      lesion. Maladaptive intraspinal plasticity is thought to contribute to the
      temporal development of AD, and experimental approaches that reduce such
      plasticity mitigate the severity of AD. The mammalian target of rapamycin (mTOR)
      has gained interest as a mediator of plasticity, regeneration, and nociceptor
      hypersensitivity in the injured spinal cord. Based on our preliminary data that
      prolonged rapamycin (RAP) treatment markedly reduces mTOR activity in the cord
      weeks after high-thoracic (T4) spinal transection, we sought to determine whether
      RAP could modulate AD development by impeding intraspinal plasticity. Naive and
      injured rats were administered RAP or vehicle every other day, beginning
      immediately after injury for four weeks, and hemodynamic monitoring was conducted
      to analyze the frequency of spontaneously occurring AD, as well as the severity
      of colorectal distention (CRD) induced AD. Results showed that after SCI, RAP
      significantly exacerbated sustained body weight loss and caused a marked
      elevation in resting blood pressure, with average daily blood pressure rising
      above even normal naive levels within one week after injury. Moreover, RAP
      significantly increased the frequency of daily spontaneous AD and increased the
      absolute blood pressure induced by CRD at three weeks post-injury. These dynamic
      cardiovascular effects were not, however, correlated with changes in the density
      of nociceptive c-fibers or c-Fos+ neurons throughout the spinal cord, indicating
      that intraspinal plasticity associated with AD was not altered by treatment.
      These findings caution against the use of RAP as a therapeutic intervention for
      SCI because it evokes toxic weight loss and exacerbates cardiovascular
      dysfunction perhaps mediated by increased peripheral nociceptor sensitivity
      and/or vascular resistance.

PMID- 29205091
TI  - Polysomnographic Oxygen Saturation Findings for Preteen Children versus
      Adolescents.
AB  - Objective Home oximetry is commonly used to screen for obstructive sleep apnea
      (OSA) in children; however, normal oxygen desaturation levels by disease severity
      are not well known. It was our objective to determine if oxygen saturation levels
      differed by OSA severity category in children and if these differences were
      similar for preteen children and adolescents. Study Design Retrospective case
      series of children undergoing polysomnography from September 2011 to July 2015.
      Setting Tertiary pediatric hospital. Subjects and Methods Six- to 18-year-olds
      (preteen, 6-12 years old; adolescent, 13-18 years old). Chi-square, Wilcoxon rank
      sum test, and Kruskal-Wallis testing were used to compare variables between age
      groups. Results The study included 342 children with a mean age of 11.3 +/- 2.4
      years (range, 6.5-17.5) and a mean body mass index of 25.6 +/- 9.2 kg/m2 (78 +/-
      29 percentile); 61% were white, 35% were black, and 4% were other or unknown. Of
      the children, 48% were female, and this was not a significant difference between
      age groups ( P = .81). Overall, 50% of the children had no OSA, 32% mild, 10%
      moderate, and 8% severe. When compared with the younger children, the adolescents
      had a longer sleep time ( P = .014) and a higher mean obstructive apnea-hypopnea
      index (3.53 +/- 5.1 vs 3.03 +/- 6.1 events per hour, P = .02). The 3% and 4%
      oxygen desaturation indices were not significantly different between age groups
      when accounting for OSA severity. Conclusion Adolescents have longer sleep times
      and higher obstructive apnea-hypopnea indexes than preteens, but oxygen
      saturations and desaturation indices were similar. This supports current triage
      algorithms for children with OSA, as we found no significant age-based
      differences.

PMID- 29205092
TI  - Biocompatibility of subcutaneously implanted marine macromolecules cross-linked
      bio-composite scaffold for cartilage tissue engineering applications.
AB  - There is an intense interest in developing innovative biomaterials which support
      the invasion and proliferation of living cells for potential applications in
      tissue engineering and regenerative medicine. Present study demonstrated the in
      vivo biocompatibility and toxicity of a macromolecules cross-linked biocomposite
      scaffold composed of hydroxyapatite, alginate, chitosan and fucoidan abbreviated
      as HACF. The in vivo biocompatibility and toxicity of HACF scaffold were tested
      by comparing them with those of a biocompatible surgical metal implant (SMI) in a
      subcutaneous rat model. Following the implantation, animals were sacrificed and
      the scaffolds were resected at 1st, 4th, and 8th weeks; the surrounding tissue
      along with the implant was removed to evaluate its biocompatibility. The effects
      of implanted biomaterial scaffolds on vital organ systems such as liver, kidney,
      etc., have been studied by hematology and serum biochemistry. The activities of
      pro-inflammatory marker enzymes such as COX, 5-LOX, 15-LOX, and NOS were normal
      in rats implanted with HACF scaffold. Hematological parameters, antioxidant and
      lipid peroxidation status were also found to be normal in implanted rats same as
      that of control and SMI. The modulatory effect of implanted scaffold over
      inflammatory and stress signaling cascades were confirmed by the normalized mRNA
      expressions of NF-kappaB, TNF-alpha and IL-6. The histopathological analysis of
      liver, kidney and tissue support our results. Taken together, these results
      demonstrated that HACF biocomposite scaffold signifies its suitability for
      further research as a scaffold material for cartilage tissue engineering
      applications.

PMID- 29205093
TI  - Impact of microbial proteases on biotechnological industries.
AB  - The demand of enzymes in industrial sectors is increasing rapidly due to their
      economical and ecological advantages. Micro-organisms produce different types of
      extracellular enzymes for maintaining their own metabolism, defense, and normal
      physiological condition. Among several enzymes, proteases have gained special
      attention in industrial sectors. Several sources of extracellular enzymes are
      reported by various researchers, but enzymes obtain from microbial sources have
      high demand in industries due to lower cost, high production rate, availability,
      stability, and diversity. Among micro-organism, bacteria and fungi are reported
      to be good sources of different types of proteases such as alkaline protease,
      cysteine protease, aspartate protease, and metallo protease. In this review, we
      have summarized the available information about the sources of bacterial and
      fungal proteases, their purification strategies and their temperature and pH
      optima. Due to huge competition, companies are trying to reduce their
      manufacturing cost and that's why microbial sources of enzymes are important.
      However, genetically engineered strains or engineered proteases have much more
      importance over natural isolates/protease in industries due to higher production
      rate and other advantages. Here we have also summarized the important
      applications of protease in different industries such as, paper mill, starch
      degrading sector, food processing factories, and detergent making companies.

PMID- 29205094
TI  - Incidence of Lingual Tonsil Hypertrophy in Adults with and without Obstructive
      Sleep Apnea.
AB  - Objectives To characterize the incidence of lingual tonsil hypertrophy (LTH) in
      adults with and without obstructive sleep apnea (OSA) and to determine any
      potential correlation between them. Study Design Retrospective chart review.
      Setting Single-center database, September 2016 to April 2017. Subject and Methods
      Lingual tonsil grade (LTG) determined by awake endoscopy was collected as well as
      other physical examination findings, such as Friedman tongue position, palatine
      tonsil size, and neck circumference. STOP-BANG scores and polysomnography data
      were collected to characterize OSA. Incidence of clinically meaningful LTH
      (defined as LTG 3 and LTG 4) was compared between OSA and non-OSA groups. Results
      Ninety-three patient charts were studied in total. There was no significant
      difference between patients with and without OSA in the incidence of clinically
      meaningful LTH (OSA, 13.5%; non-OSA, 14.6%; P = .872). Patients with and without
      OSA were compared by grade: LTG 1, 13.5% (OSA) vs 35.6% (non-OSA); LTG 2, 73.1%
      (OSA) vs 48.8% (non-OSA); LTG 3, 13.5% (OSA) vs 14.6% (non-OSA). There were no
      significant correlations between OSA status and LTG (rho = 0.190, P = .069).
      Conclusion The incidence of LTH is uncommon, even among those with OSA, and does
      not seem to differ between patients with and without OSA. Neck circumference
      appears to be a better clinical indicator than lingual tonsil tissue for the
      likelihood of a patient having OSA.

PMID- 29205095
TI  - Lexical-Access Ability and Cognitive Predictors of Speech Recognition in Noise in
      Adult Cochlear Implant Users.
AB  - Not all of the variance in speech-recognition performance of cochlear implant
      (CI) users can be explained by biographic and auditory factors. In normal-hearing
      listeners, linguistic and cognitive factors determine most of speech-in-noise
      performance. The current study explored specifically the influence of visually
      measured lexical-access ability compared with other cognitive factors on speech
      recognition of 24 postlingually deafened CI users. Speech-recognition performance
      was measured with monosyllables in quiet (consonant-vowel-consonant [CVC]),
      sentences-in-noise (SIN), and digit-triplets in noise (DIN). In addition to a
      composite variable of lexical-access ability (LA), measured with a lexical
      decision test (LDT) and word-naming task, vocabulary size, working-memory
      capacity (Reading Span test [RSpan]), and a visual analogue of the SIN test (text
      reception threshold test) were measured. The DIN test was used to correct for
      auditory factors in SIN thresholds by taking the difference between SIN and DIN:
      SRTdiff. Correlation analyses revealed that duration of hearing loss (dHL) was
      related to SIN thresholds. Better working-memory capacity was related to SIN and
      SRTdiff scores. LDT reaction time was positively correlated with SRTdiff scores.
      No significant relationships were found for CVC or DIN scores with the predictor
      variables. Regression analyses showed that together with dHL, RSpan explained 55%
      of the variance in SIN thresholds. When controlling for auditory performance, LA,
      LDT, and RSpan separately explained, together with dHL, respectively 37%, 36%,
      and 46% of the variance in SRTdiff outcome. The results suggest that poor verbal
      working-memory capacity and to a lesser extent poor lexical-access ability limit
      speech-recognition ability in listeners with a CI.

PMID- 29205096
TI  - Anatomical and Functional Changes to the Colonic Neuromuscular Compartment after
      Experimental Spinal Cord Injury.
AB  - A profound reduction in colorectal transit time accompanies spinal cord injury
      (SCI), yet the colonic alterations after SCI have yet to be understood fully. The
      loss of descending supraspinal input to lumbosacral neural circuits innervating
      the colon is recognized as one causal mechanism. Remodeling of the colonic
      enteric nervous system/smooth muscle junction in response to inflammation,
      however, is recognized as one factor leading to colonic dysmotility in other
      pathophysiological models. We investigated the alterations to the neuromuscular
      junction in rats with experimental high-thoracic (T3) SCI. One day to three weeks
      post-injury, both injured and age-matched controls underwent in vivo
      experimentation followed by tissue harvest for histological evaluation.
      Spontaneous colonic contractions were reduced significantly in the proximal and
      distal colon of T3-SCI rats. Histological evaluation of proximal and distal colon
      demonstrated significant reductions of colonic mucosal crypt depth and width.
      Markers of intestinal inflammation were assayed by qRT-PCR. Specifically, Icam1,
      Ccl2 (MCP-1), and Ccl3 (MIP-1alpha) mRNA was acutely elevated after T3-SCI.
      Smooth muscle thickness and collagen content of the colon were increased
      significantly in T3-SCI rats. Colonic cross sections immunohistochemically
      processed for the pan-neuronal marker HuC/D displayed a significant decrease in
      colonic enteric neuron density that became more pronounced at three weeks after
      injury. Our data suggest that post-SCI inflammation and remodeling of the enteric
      neuromuscular compartment accompanies SCI. These morphological changes may
      provoke the diminished colonic motility that occurs during this same period,
      possibly through the disruption of intrinsic neuromuscular control of the colon.

PMID- 29205097
TI  - Migraine-Related Aural Fullness: A Potential Clinical Entity.
AB  - In this case series, we set out to describe the clinical entity of isolated,
      prolonged aural fullness (AF) and its relationship with migraine. Patients with
      isolated, persistent AF for 6 months or more were included with all possible
      etiologies ruled out. Migraine dietary and lifestyle changes and medical migraine
      prophylactic therapy were prescribed to all. Eleven patients were included (mean
      age, 52 years). Six (54%) patients fulfilled International Headache Society
      criteria for migraine with or without aura. Changes in perceived sensation of AF
      using the visual analog scale and quality of life questionnaires resulted in a
      statically significant improvement ( P < .001, 95% confidence interval [CI], 4.7
      to 6.72, and P < .001, 95% CI, -5.3 to -2.7, respectively). As such, an
      improvement of isolated, prolonged AF with migraine lifestyle changes and
      prophylactic treatment may suggest an etiological association between migraine
      and prolonged aural fullness.

PMID- 29205098
TI  - Platelet-Derived Growth Factor Receptor-Alpha Expressing Cardiac Progenitor Cells
      Can Be Derived from Previously Cryopreserved Human Heart Samples.
AB  - Cardiac progenitor cells (CPCs) are being developed as a promising treatment for
      heart failure. Although clinical trials have predominantly used donor cardiac
      biopsies to derive CPCs, a better solution could be to use previously
      cryopreserved human heart tissue. This would enable timely and convenient access
      to healthy and young heart samples for CPC production. However, few studies have
      attempted to isolate CPCs from previously cryopreserved heart tissue. In this
      study, we isolated CPCs from eight nondiseased human heart samples previously
      cryopreserved as part of the Sydney Heart Bank. Resulting cells were strongly
      positive for known fibroblast (DDR2, Vimentin), mesenchymal/CPC (PDGFRalpha,
      CD90) markers, and for pluripotency genes (SOX2, NANOG, MYC, KLF4), whereas being
      negative for the pan-hematopoietic marker (CD45). Outgrowth cells from aged
      hearts had decreased proliferative and self-renewing capacity that correlated
      with shorter telomere lengths compared with cells from young hearts. No
      telomerase activity was detected in any cells isolated. Colony-forming assays and
      fluorescence-activated cell sorting were used to enrich PDGFRalpha+/CD90+/CD31-
      CPCs. Multipotent potential was confirmed using in vitro differentiation assays
      with smooth muscle (MYH11+), endothelial cell (vWF+), and cardiomyocyte-like
      (cTnT+, alpha-actinin+) cell formation. Single cell assays demonstrated
      clonogenicity of PDGFRalpha+ CPCs with maintenance of prolonged self-renewing
      capacity (>2 months), and pluripotency gene expression at both early and late
      culture passages. Our results demonstrate that multipotent PDGFRalpha+ CPCs can
      be harvested and expanded from previously banked cryopreserved human heart
      samples. These data support cardiac tissue banking as a strategy for improved
      access to CPCs for future clinical therapies.

PMID- 29205099
TI  - Adiponectin-leptin ratio: A promising index to estimate adipose tissue
      dysfunction. Relation with obesity-associated cardiometabolic risk.
AB  - Obesity is currently the most extended metabolic disturbance worldwide favoring
      the development of cardiometabolic alterations such as type 2 diabetes,
      hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are
      characterized by an increase in circulating leptin concentrations, in parallel to
      a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin
      ratio has been suggested as a maker of adipose tissue dysfunction. This emerging
      biomarker correlates with insulin resistance better than adiponectin or leptin
      alone, or even HOMA and is decreased with increasing number of metabolic risk
      factors having been proposed as a predictive marker for the MS. Moreover, the
      adiponectin/leptin ratio is negatively correlated with markers of low-grade
      chronic inflammation. In this sense, an increase in this ratio has been related
      with reduced atherosclerosis risk as well as with a decreased risk of some types
      of cancer in epidemiological studies. In this commentary we propose new cutoffs
      to estimate obesity- and MS-associated cardiometabolic risk according to the
      adiponectin/leptin ratio and discuss different therapeutic strategies to increase
      this promising biomarker of metabolic risk.

PMID- 29205101
TI  - Corrigendum.

PMID- 29205100
TI  - Role of Cortical Auditory Evoked Potentials in Reducing the Age at Hearing Aid
      Fitting in Children With Hearing Loss Identified by Newborn Hearing Screening.
AB  - Recording of free-field cortical auditory evoked potential (CAEP) responses to
      speech tokens was introduced into the audiology management for infants with a
      permanent childhood hearing impairment (PCHI) during 2011-2015 at a U.K. service.
      Children with bilateral PCHI were studied from two sequential cohorts. Thirty
      four children had followed an audiology pathway prior to CAEP introduction, and
      44 children followed a pathway after the introduction of CAEP and were tested
      with unaided and aided CAEP responses. Data analysis explored the age of
      diagnosis, hearing aid fitting, and referral for cochlear implant (CI) assessment
      for each of these groups. CAEP offered a novel educative process for the parents
      and audiologists supporting decision-making for hearing aid fitting and CI
      referral. Delays in hearing aid fitting and CI referral were categorized as being
      due to the audiologist's recommendation or parental choice. Results showed that
      the median age of hearing aid fitting prior to CAEP introduction was 9.2 months.
      After the inclusion of CAEP recording in the infant pathways, it was 3.9 months.
      This reduction was attributable to earlier fitting of hearing aids for children
      with mild and moderate hearing losses, for which the median age fell from 19 to 5
      months. Children with profound hearing loss were referred for CI assessment at a
      significantly earlier age following the introduction of CAEP. Although there has
      also been a national trend for earlier hearing aid fitting in children, the
      current study demonstrates that the inclusion of CAEP recording in the pathway
      facilitated earlier hearing aid fitting for milder impairments.

PMID- 29205102
TI  - CRISPR/Cas9 Editing of the Mouse Thra Gene Produces Models with Variable
      Resistance to Thyroid Hormone.
AB  - BACKGROUND: Resistance to thyroid hormone due to THRA mutations (RTHalpha) is a
      recently discovered genetic disease, displaying important variability in its
      clinical presentation. The mutations alter the function of TRalpha1, one of the
      two nuclear receptors for thyroid hormone. METHODS: The aim of this study was to
      understand the relationship between specific THRA mutations and phenotype.
      CRISPR/Cas9 genome editing was used to generate five new mouse models of
      RTHalpha, with frameshift or missense mutations. RESULTS: Like human patients,
      mutant mice displayed a hypothyroid-like phenotype, with altered development.
      Phenotype severity varied between the different mouse models, mainly depending on
      the ability of the mutant receptor to interact with transcription corepressor in
      the presence of thyroid hormone. CONCLUSION: The present mutant mice represent
      highly relevant models for the human genetic disease which will be useful for
      future investigations.

PMID- 29205103
TI  - Sharpening randomization-based causal inference for 22 factorial designs with
      binary outcomes.
AB  - In medical research, a scenario often entertained is randomized controlled 22
      factorial design with a binary outcome. By utilizing the concept of potential
      outcomes, Dasgupta et al. proposed a randomization-based causal inference
      framework, allowing flexible and simultaneous estimations and inferences of the
      factorial effects. However, a fundamental challenge that Dasgupta et al.'s
      proposed methodology faces is that the sampling variance of the randomization
      based factorial effect estimator is unidentifiable, rendering the corresponding
      classic "Neymanian" variance estimator suffering from over-estimation. To address
      this issue, for randomized controlled 22 factorial designs with binary outcomes,
      we derive the sharp lower bound of the sampling variance of the factorial effect
      estimator, which leads to a new variance estimator that sharpens the finite
      population Neymanian causal inference. We demonstrate the advantages of the new
      variance estimator through a series of simulation studies, and apply our newly
      proposed methodology to two real-life datasets from randomized clinical trials,
      where we gain new insights.

PMID- 29205104
TI  - COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of
      Cortical Pyramidal Neuronal Differentiation.
AB  - BACKGROUND: Thyroid hormone is critical for normal brain development and acts in
      a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency,
      can lead to irreversible impairment of brain and sensory development. Chicken
      ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal
      development, is essential to achieve normal brain structure. Thyroid hormone
      stimulation of gene expression is inversely correlated with the level of COUP-TF1
      expression. METHODS: An in vitro method of differentiating mouse embryonic stem
      (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1
      on thyroid hormone signaling in brain development. mES cells were cultured and
      differentiated in specific conditioned media, and a high percentage of nestin
      positive progenitor neurons in the first stage, and cortical neurons in the
      second stage, was obtained with characteristic neuronal firing. RESULTS: The
      number of nestin-positive progenitors, as determined by fluorescence-activated
      cell sorting analysis, was significantly greater with triiodothyronine (T3)
      treatment compared to control (p < 0.05). T3 enhanced the expression of cortical
      neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of
      nestin-positive progenitors was reduced compared to control (p < 0.05), but the
      number increased with T3 treatment. The mRNA of cortical neuronal gene markers
      was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression
      of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of
      differentiation, compared to control cells, at day 22. Furthermore, after COUP
      TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced
      compared to cells expressing COUP-TF1. CONCLUSION: These results indicate that
      COUP-TF1 plays an important role in modulating the timing and magnitude of T3
      stimulated gene expression required for normal corticogenesis.

PMID- 29205105
TI  - Epidemiology: Past, Present, and Future Impacts on Understanding Disease Dynamics
      and Improving Plant Disease Management-A Summary of Focus Issue Articles.
AB  - Epidemiology has made significant contributions to plant pathology by elucidating
      the general principles underlying the development of disease epidemics. This has
      resulted in a greatly improved theoretical and empirical understanding of the
      dynamics of disease epidemics in time and space, predictions of disease outbreaks
      or the need for disease control in real-time basis, and tactical and strategic
      solutions to disease problems. Availability of high-resolution experimental data
      at multiple temporal and spatial scales has now provided a platform to test and
      validate theories on the spread of diseases at a wide range of spatial scales
      ranging from the local to the landscape level. Relatively new approaches in plant
      disease epidemiology, ranging from network to information theory, coupled with
      the availability of large-scale datasets and the rapid development of computer
      technology, are leading to revolutionary thinking about epidemics that can result
      in considerable improvement of strategic and tactical decision making in the
      control and management of plant diseases. Methods that were previously restricted
      to topics such as population biology or evolution are now being employed in
      epidemiology to enable a better understanding of the forces that drive the
      development of plant disease epidemics in space and time. This Focus Issue of
      Phytopathology features research articles that address broad themes in
      epidemiology including social and political consequences of disease epidemics,
      decision theory and support, pathogen dispersal and disease spread, disease
      assessment and pathogen biology and disease resistance. It is important to
      emphasize that these articles are just a sample of the types of research projects
      that are relevant to epidemiology. Below, we provide a succinct summary of the
      articles that are published in this Focus Issue .

PMID- 29205107
TI  - Images in Vascular Medicine: Systemic cardiovascular inflammation associated with
      autoimmune disease.

PMID- 29205106
TI  - Differential Expression of Cholinergic System Components in Human Induced
      Pluripotent Stem Cells, Bone Marrow-Derived Multipotent Stromal Cells, and
      Induced Pluripotent Stem Cell-Derived Multipotent Stromal Cells.
AB  - The components of the cholinergic system are evolutionary very old and conserved
      molecules that are expressed in typical spatiotemporal patterns. They are
      involved in signaling in the nervous system, whereas their functions in
      nonneuronal tissues are hardly understood. Stem cells present an attractive
      cellular system to address functional issues. This study therefore compared human
      induced pluripotent stem cells (iPSCs; from cord blood endothelial cells),
      mesenchymal stromal cells derived from iPSCs (iPSC-MSCs), and bone marrow-derived
      MSCs (BM-MSCs) from up to 33 different human donors with respect to gene
      expressions of components of the cholinergic system. The status of cells was
      identified and characterized by the detection of cell surface antigens using flow
      cytometry. Acetylcholinesterase expression in iPSCs declined during their
      differentiation into MSCs and was comparably low in BM-MSCs.
      Butyrylcholinesterase was present in iPSCs, increased upon transition from the
      three-dimensional embryoid body phase into monolayer culture, and declined upon
      further differentiation into iPSC-MSCs. In BM-MSCs a notable
      butyrylcholinesterase expression could be detected in only four donors, but was
      elusive in other patient-derived samples. Different nicotinic acetylcholine
      receptor subunits were preferentially expressed in iPSCs and during early
      differentiation into iPSC-MSCs, low expression was detected in iPS-MSCs and in BM
      MSCs. The m2 and m3 variants of muscarinic acetylcholine receptors were detected
      in all stem cell populations. In BM-MSCs, these gene expressions varied between
      donors. Together, these data reveal the differential expression of cholinergic
      signaling system components in stem cells from specific sources and suggest the
      utility of our approach to establish informative biomarkers.

PMID- 29205108
TI  - Contributions of the Hydrophobic Helix 2 of the Bordetella pertussis CyaA
      hemolysin to Membrane Permeabilization.
AB  - BACKGROUND: Adenylate cyclase (CyaA) is one of the major virulence factors of
      Bordetella pertussis that plays a key role in whooping cough pathogenesis. A
      putative transmembrane helical hairpin (alpha2-loop-alpha3), encompassing
      residues 529-594 of CyaA hemolysin (CyaA-Hly) domain, was previously proposed to
      be crucially involved in hemolytic activity against target erythrocytes.
      OBJECTIVE: The main objective of this study was to gain more insight into
      membrane permeabilization of this toxin. Membrane-permeabilizing abilities of the
      purified 130-kDa CyaA-Hly and synthetic peptides corresponding to the helical
      component of interest, were evaluated. METHODS: Synthetic peptides corresponding
      to the critical helical component, i.e. alpha2 (W528-G550), alpha3 (G568-R594)
      and alpha2-loop-alpha3 (W528-R594), were examined on various membrane models in
      comparison with the purified 130-kDa CyaA-Hly. The peptides were commercially
      synthesized and the purified toxin was obtained from recombinant plasmid
      construction and expression in Escherichia coli, followed by purification via
      immobilized-metal affinity chromatography. Membrane permeabilization or hemolysis
      of the peptides or the purified toxin were determined by liposomal leakage,
      hemolysis assays and atomic force microscopy (AFM) imaging. RESULTS: Our results
      showed that the truncated 130-kDa CyaA-Hly, the synthetic peptides alpha2, alpha3
      and the alpha2-loop-alpha3 hairpin exhibited distinct membrane-permeabilizing
      capacities in different membrane models. We demonstrated that the CyaA-Hly toxin
      and the peptides, especially the alpha2 peptide, caused nonspecific liposomal
      leakage as monitored by fluorescence dequenching of sulforhodamine B-loaded lipid
      vesicles. Notably, alpha2 peptide showed a predominant effect of membrane
      permeabilization when compared to alpha2-loop-alpha3 hairpin and alpha3 peptides.
      In addition, AFM imaging demonstrates lipid membrane disruption induced by the
      CyaA-Hly toxin or the peptidic alpha2-loop-alpha3 hairpin. CONCLUSION: Overall,
      the study provides the supporting evidence that the putative helical alpha2-loop
      alpha3 hairpin could interact with the lipid membranes while the helical alpha2
      peptide strongly induced liposomal leakage and hemolysis, as compared with the
      helical alpha3 or the alpha2-loop-alpha3 peptides, suggesting that the helix 2
      from the hydrophobic region of CyaA-Hly is a crucial component that contributes
      to membrane permeabilization.

PMID- 29205109
TI  - New Treatments for Allergy: Advances in Peptide Immunotherapy.
AB  - BACKGROUND: Nowadays, allergen-specific immunotherapy (AIT) is the only treatment
      able to modulate the course of allergic diseases. Although it has been applied
      for the last 100 years, treatment with whole allergen extracts is not without its
      drawbacks: AIT can cause local and systemic adverse events and may produce new
      IgE sensitization against other allergens present in the extract. Furthermore,
      the lengthy treatment duration (3-5 years), frequent administration, and high
      cost of treatment are other disadvantages. For these reasons, there is a need for
      safer and more effective AIT strategies. One promising approach is the use of
      synthetic peptides representing the B- or T-cell epitopes of allergens.
      OBJECTIVE: This review summarizes the main advances in peptide immunotherapy,
      from preclinical models to early clinical trials, focusing on house dust mite,
      bee venom, cat allergy, and Oleaceae pollinosis. RESULTS: Following an extensive
      review of the relevant literature, we summarize how peptide therapies may change
      the course of allergic diseases and promote allergen tolerance, thereby
      ameliorating the main disadvantages of AIT. Although the molecular mechanisms
      involved are not yet fully defined, they seem to depend on structure, length,
      peptide sequence, and route of administration. This novel immunotherapy has been
      demonstrated to modulate the immune system, promoting regulatory T-cell induction
      and Th2 inhibition. This tolerance-inducing potential has led this therapy to be
      termed SPIRE (synthetic peptide immuno-regulatory epitopes). CONCLUSION:
      Experimental models and clinical trials have demonstrated the usefulness of SPIRE
      treatment to cure these diseases, opening a new era in allergen therapeutics.

PMID- 29205111
TI  - A Review on Oral Liquid as an Emerging Technology in Controlled Drug Delivery
      System.
AB  - BACKGROUND: The Oral Liquid Drug Delivery System (OLDDS) remains the primary
      choice of dosage form, though challenging, for the pharmaceutical scientists. In
      the last two decades, Oral Liquid Controlled Release (OLCR) formulation has
      gained a lot of attention because of its advantages over the conventional dosage
      forms. METHOD: The world of nanotechnology has paved multiple ways to administer
      the drug through oral cavity in liquid dosage form with an additional advantage
      of control over the release. In the current study, the various approaches towards
      the same have been discussed comprehensively to understand the different
      mechanisms of OLCR. CONCLUSION: This review also emphasizes on the existing
      techniques and the developments that have been made to improve on its efficacy
      including various formulation related factors. It also provides valuable insights
      into the role of polymers in the development of OLCR formulation that can be used
      in the management of Gastroesophageal Reflux Disease (GERD).

PMID- 29205112
TI  - Ensuring the Consistency of Biosimilars.
AB  - BACKGROUND: Biological products are subject to constant reappraisal by regulatory
      agencies and pharmaceutical companies once they have entered the market, since
      every improvement in their manufacturing process has the potential to alter the
      basic properties of these molecules. METHODS: Narrative review focusing on
      scientific literature as well as legal documents from regulatory agencies.
      RESULTS: Evaluating the impact of each manufacturing change of these drugs
      requires rigorous analyses in proportion to the anticipated risk of inducing more
      or less molecular micro-heterogenicity. There are currently more than 30
      biosimilars of TNF-alpha blockers at different stages of testing, each with a
      specific manufacturing process. Although the initial demonstration of
      biosimilarity is now a well-established exercise, it does not guarantee that
      successive manufacturing changes will not result in a widening gap between
      drifted/evolved innovators and drifted/evolved biosimilars, as well as among the
      different biosimilars of a given original biologic. CONCLUSION: Given the
      structural complexity of TNF-alpha blockers-as well as of other biologic drugs
      included in the armamentarium of systemic inflammatory diseases-regulatory
      agencies should make available to the practitioner, in a simple and constantly
      updated way, all available data regarding quality standards of both original
      molecules and biosimilars. Furthermore, they should strive to guarantee that,
      once a compound has received approval, it maintains a level of consistency
      throughout its commercial life in order to maintain and increase confidence in
      these valuable drugs.

PMID- 29205110
TI  - Peptide Mediated Brain Delivery of Nano- and Submicroparticles: A Synergistic
      Approach.
AB  - The brain is a complex, regulated organ with a highly controlled access
      mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a
      double-edged sword, being both its greatest strength and weakness. This weakness
      is evident when trying to target therapeutics against diseases within the brain.
      Diseases such as metastatic brain cancer have extremely poor prognosis due to the
      poor permeability of many therapeutics across the BBB. Peptides can be designed
      to target BBB receptors and gain access to the brain by transcytosis. These
      peptides (known as BBB-shuttles) can carry compounds, usually excluded from the
      brain, across the BBB. BBB-shuttles are limited by poor loading of therapeutics
      and degradation of the peptide and cargo. Likewise, nano- submicro- and
      microparticles can be fine-tuned to limit their degradation and with high loading
      of therapeutics. However, most nano- and microparticles' core materials
      completely lack efficient targeting, with a few selected materials able to cross
      the BBB passively. Combining the selectivity of peptides with the high loading
      potential of nano-, microparticles offers an exciting strategy to develop novel,
      targeted therapeutics towards many brain disorders and diseases. Nevertheless, at
      present the field is diverse, in both scope and nomenclature, often with
      competing or contradictory names. In this review, we will try to address some of
      these issues and evaluate the current state of peptide mediated nano,
      microparticle transport to the brain, analyzing delivery vehicle type and peptide
      design, the two key components that must act synergistically for optimal
      therapeutic impact.

PMID- 29205113
TI  - Immobilization techniques applied to the development of biocatalysts for the
      synthesis of nucleoside analogue derivatives.
AB  - BACKGROUND: Nucleoside analogue (NAs) derivatives comprise a large family of
      pharmaceuticals clinically used as antitumoral and antiviral compounds.
      Originally, the production of NAs involved chemical synthesis, but a greener
      bioproduction alternative exists and involves the use of enzymes that catalyze
      transglycosylation reactions between modified purinic or pyrimidinic bases and
      sugars. To be considered as an option for industrial application, it is vital to
      immobilize these biocatalysts. METHODS: This article describes current
      methodologies for whole cell and protein immobilization mostly applied to the
      synthesis of important NAs. Immobilization describes ways of cell or enzyme
      confinement in diverse surfaces or matrixes. It is important to be familiar with
      the variety of matrixes and supports available prior to biocatalyst
      immobilization so the most adequate can be selected for the purpose sought.
      RESULTS: From the different articles compiled, it can be acknowledged that the
      main methods for protein or cell stabilization are immobilization by adsorption,
      covalent, cross-linking and entrapment. The most widely used matrixes and
      supports are agar, alginate, polyacrylamide, sepharose derivatives, and acrylic
      resins, among others. Protein or cell stabilization has the advantage of
      stabilizing immobilization, favoring their facile separation from the reaction
      medium for further reuse and also making the purification of the final product
      easier. Moreover, biocatalyst stabilization allows a facile estimation of the
      economic cost of the bioprocess and of an eventual scale-up, being a basic
      requirement for industrial application. CONCLUSION: In order to achieve
      successful biocatalyst immobilization, parameters such as biocatalyst stability,
      mechanical resistance, and reusability should be considered. This review
      describes and summarizes the methods used for the immobilization of biocatalysts
      for the synthesis of NAs in the last years.

PMID- 29205114
TI  - The Experience with Biosimilars of Infliximab in Inflammatory Bowel Disease.
AB  - BACKGROUND: biosimilars are similar versions of existing innovator biologic
      agents but with distinct manufacturing processes. They were approved in
      inflammatory bowel disease (IBD) by extrapolation of indication from rheumatic
      diseases. As regulatory requirements for biosimilar approval focus on pre
      clinical evidence of similarity rather than clinical data on efficacy, safety and
      immunogenicity, it is critical to review clinical evidence supporting their use
      in IBD in order to overcome reluctance from patients and clinicians alike.
      OBJECTIVE: to review clinical studies using infliximab (IFX) biosimilars in IBD.
      METHOD: we reviewed PubMed for original articles published up to July 1st 2017,
      reporting data on efficacy and/or safety of IFX biosimilars in IBD. RESULTS: 23
      observational studies were found, 12 of them assessing switch from IFX originator
      to biosimilar and 17 assessing induction therapy with IFX biosimilar. Efficacy,
      safety and immunogenicity were compared, generally yielding similar results for
      originator and biosimilar IFX. So far only one randomized controlled trial
      assessed switching from originator to biosimilar IFX and it was not powered to
      show similarity in IBD. Ongoing trials are comparing IFX biosimilar and
      originator head to head in patients in remission, as well as switch versus
      reverse-switch. Current IBD clinical guidelines are discussed as well as future
      perspectives for biosimilars in IBD. CONCLUSION: observational studies seem to
      confirm biosimilarity in a real-world clinical setting. Current trials are
      expected to elucidate the remaining doubts about clinical biosimilarity.

PMID- 29205115
TI  - The Overlap Between Binge Eating Behaviors and Polycystic Ovarian Syndrome: An
      Etiological Integrative Model.
AB  - Studies indicate that Polycystic Ovarian Syndrome (PCOS) features (e.g. insulin
      instability, food cravings, overproduction of androgens and menstrual
      irregularities) are associated with increased appetite, impaired impulse control
      and feelings of body dissatisfaction. Counter intuitively, binge eating behaviors
      have been shown to reinforce PCOS symptomatology, precipitating concurrently body
      dissatisfaction, weight gain, insulin instability and overproduction of
      androgens. The present systematic literature review aspires to investigate the
      relationship between binge eating, in the broader context of eating disorder
      behaviors, and Polycystic Ovarian Syndrome (PCOS), taking into account shared
      characteristics between EDs (Eating Disorders) and PCOS. To address this aim, the
      PRISMA guidelines are adopted. A total of 21 studies, which investigated the
      presence of binge eating in PCOS population and the presence of PCOS in EDs
      population, were synthesized. Findings suggested that an increased prevalence of
      binge eating has been reported in women with Polycystic Ovarian Syndrome (PCOS);
      and that women suffering from BN (Bulimia Nervosa) and BED (Binge Eating
      Disorder) are more likely to display polycystic ovaries. Further research on
      their shared liability is required in order to inform more efficient prevention
      and treatment initiatives for populations presenting with comorbid features.

PMID- 29205116
TI  - Antioxidant Activity, alpha-glucosidase Inhibitory Activity and Chemoprotective
      Properties of Rhododendron brachycarpum Leaves Extracts.
AB  - BACKGROUND: Rhododendron brachycarpum (RB) is a genus of flowering plants
      generally used for traditional medicine in Korea to treat hypertension,
      neuralgia, and sterility. Previous studies have shown that RB extract alleviate
      inflammation and antimicrobial activity. OBJECTIVE: In this study, the effects of
      RB and its different fractions (n-hexane, ethyl-acetate and n-butanol) on
      antioxidant activity, DNA damage prevention and the activity of alpha-glucosidase
      were studied. RESULTS: The antioxidant ability of RB was investigated in vitro,
      including that of DPPH-radical and reducing power. As expected, scavenging effect
      against DPPH-radical of ethyl acetate fraction (IC50 = 17.7 +/- 0.5 ug/ml) of RB
      had the highest DPPH radical scavenging activity, and it was superior to the
      positive control, butylated hydroxytoluene (BHT) (IC50 = 80.8 +/- 1.5 ug/ml). And
      the reducing power of RB was 3.18 at 1.0 mg/ml. Meanwhile, the alpha-glucosidase
      inhibitory activity and prevention of oxidation stress-induced DNA damage were
      also highest in the ethyl acetate fraction. Pretreatment of pancreatic beta-cells
      from Syrian golden hamster (HIT-TI5) with the ethyl acetate fraction at
      concentrations of 300 ug/ml significantly protected the cells from high glucose
      induced cell death. CONCLUSION: Our results indicate that ethyl acetate fraction
      of RB leaves extract has strong antioxidant, alpha-glucosidase, and prevention of
      DNA damage activities, and furthermore, ethyl acetate fraction significantly
      protected the cells from high glucose-induced cell death.

PMID- 29205117
TI  - Characterization of Optimized Functional-Complementary Dual Insulinotorpic
      Peptide rolGG.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide
      (GIP) play a similar but complementary role in the regulation of glucose levels
      in islet beta-cells. This study was aimed to develop a fusion peptide, which
      combines 4 tandem repeated GLP-1 and 4 tandem repeated GIP (4rolGG), and to
      investigate its therapeutic effect on type 2 diabetes using a diabetic mice
      model. METHODS: A 4rolGG expression plasmid was constructed and expressed in BL21
      (DE3). By inducting with IPTG, 4rolGG was expressed at a high level, which was
      confirmed by SDS-PAGE electrophoresis and Western Blotting. Subsequently, 4rolGG
      was purified by Ni-NTA affinity chromatography and the purity of 4rolGG was up to
      90%. RESULT AND CONCLUSION: After oral administration of 4rolGG for 4 weeks,
      streptozotocin-induced diabetic mice showed a dramatic reduction in the levels of
      plasma glucose, GHbA1C, TC and TG, while the insulin levels were increased
      significantly.

PMID- 29205118
TI  - Depression and Medication Adherence in Patients on Hemodialysis.
AB  - BACKGROUND: Depression is highly prevalent in End Stage Renal Disease (ESRD) and
      is the most common psychiatric disorder in this population. Depression is
      associated with a lack of adherence to hemodialysis (HD) treatment regimens and
      increased morbidity and mortality. METHODS: A descriptive secondary correlational
      analysis of 118 patients on chronic HD was conducted to determine the prevalence
      of depression and its relationship to adherence to blood pressure (BP) regimens
      (fluid adherence, HD and BP medication adherence). RESULTS: Approximately 80% of
      the sample was found to have moderate depression. Depression was found to be
      significantly related to BP medication nonadherence at baseline (r = .239, p =
      .01 and at 12 weeks (r = .20, p = .027). CONCLUSION: Given the high prevalence of
      depression and its association with BP medication nonadherence, patients on
      chronic HD should be routinely assessed for depression and offered validated
      treatment regimens. Depression is a modifiable risk factor, and interventions
      that address depression in conjunction with adherence to BP regimens need to be
      tested in the HD population.

PMID- 29205119
TI  - Activity of Rifabutin and Hemi-synthetic Derivatives Against Mycobacterium
      abscessus.
AB  - BACKGROUND: Mycobacterium abscessus causes a wide range of clinical diseases that
      are difficult to treat. This microorganism is resistant not only to the classical
      antituberculosis agents but also to most of the antimicrobials that are currently
      available, resulting in limited therapeutic options and treatment failure. This
      scenario stresses the need to search for new drugs with activity against M.
      abscessus. OBJECTIVE: To evaluate in vitro the antimycobacterial activity and
      cytotoxicity of rifabutin (RFB 1) and ten derivatives (2-11) against M. abscessus
      ATCC 19977. METHOD: The minimum inhibitory concentration (MIC) of the molecules
      was determined by the microdilution broth method according to the guideline
      described in CLSI. The toxicity evaluation was carried in 96-well microplates,
      using the cell line J774A.1 (ATCC TIB-67). RESULT: From the eleven molecules
      tested, RFB 1 and RFB 4 were the compounds showing higher activities against M.
      abscessus, with MICs of 0.9 and 1.0 uM, respectively. The R1 and R2 moieties seem
      to have deciding influence over the final activity. Furthermore, N-oxide
      derivatives 9, 10, and 11 were also active against M. abscessus, with MICs of 7.2
      uM, 1.8 uM and 3.8 uM, respectively. An explanatory hypothesis for the better
      activities of compounds RFB 1, RFB 4, RFB 10 and RFB 11 considers the likely
      hydrogen bonding between ligands and receptor, balancing the global flexibility
      and interaction energies. RFB 1 and its most effective derivatives were found to
      be not toxic. CONCLUSION: Besides RFB 1, its derivatives 4, 10 and 11 show
      potential for clinical development in the M. abscessus treatment.

PMID- 29205120
TI  - Synthesis and in vitro Antioxidant Activity Study of Some Novel Substituted
      Piperazinyl Flavone Compounds.
AB  - BACKGROUND: A new series of 13 piperazinyl flavone derivatives has been
      synthesized and examined for their in vitro antiradical and antioxidant
      activities in response to the pharmacy industry's increasing demand for new non
      toxic anti-inflammatory and anticancer drugs. METHOD: Their antioxidant activity
      was evaluated by the reactive oxygen species (ROS) scavenging assays, 2,2
      diphenyl-1-picrylhydrazyl free radical (DPPH*) and 2,2'-azino-bis(3-
      ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS+*) scavenging assays,
      and the ferric reducing antioxidant potency (TAC) method, and was compared to
      known positive controls, herbal infusions, and penicillins. Chemiluminescence,
      spectrophotometry, electron spin resonance (ESR) and 5,5-dimethyl-1-pyrroline-1
      oxide (DMPO) as the spin trap were the measurement techniques. RESULT: It was
      seen that synthesized compounds have a wide spectrum of antioxidant property.
      Some of the test compounds proved to be extremely efficient scavengers of H2O2
      exhibiting, in some cases, EC50 of about 2 uM. The values of antioxidant status
      (TAS) were in the range of 49 +/- 3.9 to 1283 +/- 51.3 uM TE/g (TE = Trolox
      equivalent) and were lower than that of butylated hydroxytoluene (BHT) (1304 +/-
      43.2 uM TE/g) and green tea (1356 +/- 40.0 uM TE/g), but for several synthesized
      compounds, they were higher than chamomille infusion and penicillins. Ferric
      reducing antioxidant powers (TAC) for the piperazinyl flavone derivatives were in
      the range 7 +/- 0.5 to 104 +/- 0.6 uM TE/g and were weaker than that of BHT (217
      +/- 5.3 uM TR/g ). CONCLUSION: Carboxylic or hydroxamic acid substituted
      piperazinyl flavones are potentially active as antioxidants, thus may be
      suggested as pharmacologically interesting ones.

PMID- 29205121
TI  - Synthesis and Structure-Activity Relationship; Exploration of some Potent Anti
      Cancer Phenyl Amidrazone Derivatives.
AB  - BACKGROUND: Amidrazones have been reported to have significant anti-tumor
      properties against several cancer cell lines. OBJECTIVES: The current project
      aims to profile the structure-anticancer activity relationship of phenyl
      amidrazons. METHODS: Fifteen phenyl-amidrazone-piperazine derivatives were
      prepared and tested against four cancer cell lines (leukemia, prostate, breast
      and colon cancers). RESULTS: Six compounds illustrated low micromolar anticancer
      IC50 values, while the remaining compounds were either inactive or of moderate
      potencies. All compounds were virtually nontoxic against normal fibroblast cells.
      CONCLUSION: Docking into the oncogenic kinase bcr/abl illustrated the critical
      importance of (i) phalogen substituent on the ligand's phenyl ring and (ii) the
      presence of positive ionizable moiety at the ligand's piperazine fragment for
      anticancer activity.

PMID- 29205122
TI  - PARP Inhibitors in Epithelial Ovarian Cancer.
AB  - BACKGROUND: Ovarian cancer remains the most common lethal gynecologic malignancy.
      The therapeutic gains with the use of traditional cytotoxic chemotherapy in
      advanced stage disease remain limited, reflecting the need for novel therapies.
      Poly(ADP-ribose) polymerase (PARP) inhibitors have recently demonstrated a
      significant therapeutic effect in patients with recurrent, high grade serous
      ovarian cancer, both in the treatment of existing disease and in prolonging the
      disease-free interval. OBJECTIVE: The purpose of this article is to discuss PARP
      inhibitor use in patients with advanced stage ovarian cancer, and to extensively
      review the existing clinical literature and related patents. METHODS: A
      comprehensive PUBMED literature review was conducted to identify all published
      phase 2 and phase 3 clinical trials involving PARP inhibitors in advanced
      epithelial ovarian cancer. Further, several patents related to PARP inhibitor
      use, companion diagnostic tests, and the development of biomarkers to predict
      PARP inhibitor responsiveness are described. RESULTS: PARP inhibitors have
      demonstrated significant clinical activity in both BRCA deficient and wild-type
      patient cohorts, with all three FDA-approved PARP inhibitors demonstrating
      efficacy irrespective of BRCA mutation status in patients with advanced
      epithelial ovarian cancer. CONCLUSION: PARP inhibitors have emerged as an
      exciting new drug class in the treatment of epithelial ovarian cancer. Ongoing
      studies are aimed at improving our ability to identify ideal candidates for PARP
      inhibitor therapy, as well as to identify and target mechanisms of drug
      resistance, and novel combinatorial approaches.

PMID- 29205123
TI  - Neuronal traffic signals in tardive dyskinesia: not enough "stop" in the motor
      striatum.
AB  - Tardive dyskinesia is a disturbance in the balance between dopamine receptor
      stimulation and dopamine receptor blockade in the motor striatum, with
      hypothetically too much stimulation of supersensitive D2 receptors, resulting in
      "don't stop" signaling to motor output.

PMID- 29205124
TI  - Shewanella carassii sp. nov., isolated from surface swabs of crucian carp and
      faeces of a diarrhoea patient.
AB  - Two strains, 08MAS2251T and LZ2016-166, were isolated from diverse samples in
      China collected from the surface of crucian carp and the faeces of a diarrhoea
      patient, respectively. Both strains were pink-orange coloured, Gram-negative,
      oxidase- and catalase-positive, facultative anaerobic and motile bacteria,
      produced H2S and reduced nitrates to nitrites. Growth occurred in the presence of
      0-9 % (w/v) NaCl and at 10-42  degrees C. The optimum conditions were with 1 %
      (w/v) NaCl and at 35  degrees C. The phylogenetic tree of 16S rRNA gene
      demonstrated that strains 08MAS2251T and LZ2016-166 clustered in a distinctive
      clade next to the species Shewanella chilikensis JC5T within the genus
      Shewanella. Meanwhile, gyrB gene sequence analysis indicated that the two strains
      formed an independent branch that was clearly separate from all the other
      Shewanella species with sequence similarities from 68.49 to 95.74 %. The DNA G+C
      content of strain 08MAS2251T was 52.68 mol%. Genomic relatedness of in silico DNA
      DNA hybridization between strain 08MAS2251T and phylogenetic neighbours ranged
      from 50.5-51.8 %, below the cutoff of 70 %. In addition, corresponding average
      nucleotide identity values were between 93.01 to 93.49%, which were lower than 95
      % threshold. The major fatty acids of strain 08MAS2251T were C17 : 1omega8c (27.2
      %), iso-C15 : 0 (22.5 %), summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c;
      8.7 %), C16 : 0 (6.2 %), iso-C13 : 0 (5.6 %) and C17 : 0 (4.5 %). Based on
      phenotypic and genetic analysis, strains 08MAS2251T and LZ2016-166 are identified
      as a novel species of the genus Shewanella, for which the name Shewanellacarassii
      sp. nov. is proposed. The type strain is 08MAS2251T (=DSM 104682T=CGMCC
      1.16033T).

PMID- 29205125
TI  - Sphingopyxis nepalensis sp. nov., isolated from oil-contaminated soil.
AB  - During a study of oil-degrading bacteria, three yellow-coloured, Gram-stain
      negative, non-motile and rod-shaped bacteria, designated strains Ktm-14T, Ktm-17
      and Ktm-18, were isolated from oil-contaminated soil of Biratnagar, Morang,
      Nepal. The strains were able to grow at 15-37  degrees C, pH 4.5-10.0 and 0-2 %
      (w/v) NaCl concentration. Strains Ktm-14T, Ktm-17 and Ktm-18 were characterized
      by multiple taxonomic approaches. Based on 16S rRNA gene sequence analysis,
      strains Ktm-14T, Ktm-17 and Ktm-18 belonged to the genus Sphingopyxis and shared
      highest sequence similarity with Sphingopyxis ginsengisoliGsoil 250T (98.94 %).
      The only respiratory quinone was ubiquinone-10 and the predominant polyamine was
      spermidine. The major polar lipids were phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine,
      phosphatidylmonomethylethanolamine and sphingoglycolipids. The predominant fatty
      acids were C17 : 1omega6c, summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c), summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 0.
      The DNA G+C content values of strains Ktm-14T, Ktm-17 and Ktm-18 were 65.8, 65.9
      and 65.6 mol%, respectively. The DNA-DNA relatedness between Ktm-14T and Ktm-17
      and Ktm-18 were higher than 70 % but with closely related reference strains were
      less than 40 %. The morphological, physiological, chemotaxonomic and phylogenetic
      analyses clearly distinguished strain Ktm-14T from its closest phylogenetic
      neighbours. Thus, strain Ktm-14T represents a novel species of the genus
      Sphingopyxis, for which the name Sphingopyxisnepalensis sp. nov. is proposed. The
      type strain is Ktm-14T (=KEMB 9005-694T=KACC 19389T=JCM 32250T), and strains Ktm
      17 and Ktm-18 represent two additional strains.

PMID- 29205126
TI  - Description of Klebsiella grimontii sp. nov.
AB  - Strains previously identified as Klebsiella oxytocaphylogroup Ko6 were
      characterized by rpoB, gyrA and rrs gene sequencing, genome-sequence based
      average nucleotide identity analysis and their biochemical characteristics. rpoB
      and gyrA sequencing demonstrated that the Ko6 strains formed a well-demarcated
      sequence cluster related to, but distinct from, Klebsiella oxytoca (which
      includes strains previously labelled as K. oxytocaphylogroup Ko2) and Klebsiella
      michiganensis (Ko1). The average nucleotide identity values of Ko6 with K.
      oxytoca and K. michiganensis were 91.2 and 93.47 %, respectively. The inability
      to metabolize melezitose differentiated most of the Ko6 strains from K. oxytoca
      and K. michiganensis. Based on its genetic and phenotypic characteristics, we
      propose the name Klebsiella grimontii for the Ko6 sequence cluster, with strain
      06D021T (=CIP111401T, DSM 105630T) as the type strain. Strains of Klebsiella
      grimontii were isolated from human blood cultures, wound infections, antibiotic
      associated haemorrhagic colitis and faecal carriage.

PMID- 29205127
TI  - Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex
      demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium
      caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic
      synonyms of Mycobacterium tuberculosis.
AB  - The species within the Mycobacterium tuberculosis Complex (MTBC) have undergone
      numerous taxonomic and nomenclatural changes, leaving the true structure of the
      MTBC in doubt. We used next-generation sequencing (NGS), digital DNA-DNA
      hybridization (dDDH), and average nucleotide identity (ANI) to investigate the
      relationship between these species. The type strains of Mycobacterium africanum,
      Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and
      Mycobacterium pinnipedii were sequenced via NGS. Pairwise dDDH and ANI
      comparisons between these, previously sequenced MTBC type strain genomes
      (including 'Mycobacterium canettii', 'Mycobacterium mungi' and 'Mycobacterium
      orygis') and M. tuberculosis H37RvT were performed. Further, all available genome
      sequences in GenBank for species in or putatively in the MTBC were compared to
      H37RvT. Pairwise results indicated that all of the type strains of the species
      are extremely closely related to each other (dDDH: 91.2-99.2 %, ANI: 99.21-99.92
      %), greatly exceeding the respective species delineation thresholds, thus
      indicating that they belong to the same species. Results from the GenBank genomes
      indicate that all the strains examined are within the circumscription of H37RvT
      (dDDH: 83.5-100 %). We, therefore, formally propose a union of the species of the
      MTBC as M. tuberculosis. M. africanum, M. bovis, M. caprae, M. microti and M.
      pinnipedii are reclassified as later heterotypic synonyms of M. tuberculosis. 'M.
      canettii', 'M. mungi', and 'M. orygis' are classified as strains of the species
      M. tuberculosis. We further recommend use of the infrasubspecific term 'variant'
      ('var.') and infrasubspecific designations that generally retain the historical
      nomenclature associated with the groups or otherwise convey such characteristics,
      e.g. M. tuberculosis var. bovis.

PMID- 29205128
TI  - Antarcticibacterium flavum gen. nov., sp. nov., isolated from marine sediment.
AB  - A Gram-stain-negative, strictly aerobic, yellow-pigmented, non-gliding, oval to
      rod-shaped bacterial strain, designated JB01H24T, belonging to the family
      Flavobacteriaceae, was isolated from marine surface sediment collected from the
      Ross Sea, Antarctica. Strain JB01H24T grew at 4-40  degrees C (optimum 25-30 
      degrees C), pH 7.0-9.0 (optimum 7.5-8.0), and in the presence of 0-8 % NaCl
      (optimum 3 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain JB01H24T formed an independent linkage within the family
      Flavobacteriaceae and was closely related with the genus Gillisia. Strain
      JB01H24T exhibited 16S rRNA gene sequence similarities of 95.3-91.5 % and 94.9
      94.0 % to the type strains of the genera Gillisia and Salinimicrobium,
      respectively. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3
      (C16 : 1omega6c and/or C16 : 1omega7c), anteiso-C15 : 0, iso-C15 : 1 G and summed
      feature 9 (iso-C17 : 1omega9c and/or 10-methyl C16 : 0). The major polar lipids
      were phosphatidylethanolamine, seven unidentified lipids, two unidentified
      aminolipids and an unidentified aminophospholipid. Strain JB01H24T contained
      menaquinone-6 as the only ubiquinone. The DNA G+C content was 42.4 mol%. On the
      basis of phylogenetic, physiological and chemotaxonomic properties, strain
      JB01H24T is considered to represent a novel species of a new genus within the
      family Flavobacteriaceae, for which the name Antarcticibacterium flavum gen.
      nov., sp. nov. is proposed. The type strain of Antarcticibacterium flavum is
      JB01H24T (=GDMCC 1.1229T=KCTC 52984T).

PMID- 29205129
TI  - Dissimilar pigment regulation in Serpula lacrymans and Paxillus involutus during
      inter-kingdom interactions.
AB  - Production of basidiomycete atromentin-derived pigments like variegatic acid
      (pulvinic acid-type) and involutin (diarylcyclopentenone) from the brown-rotter
      Serpula lacrymans and the ectomycorrhiza-forming Paxillus involutus,
      respectively, is induced by complex nutrition, and in the case of S. lacrymans,
      bacteria. Pigmentation in S. lacrymans was stimulated by 13 different bacteria
      and cell-wall-damaging enzymes (lytic enzymes and proteases), but not by lysozyme
      or mechanical damage. The use of protease inhibitors with Bacillus subtilis or
      heat-killed bacteria during co-culturing with S. lacrymans significantly reduced
      pigmentation indicating that enzymatic hyphal damage and/or released peptides,
      rather than mechanical injury, was the major cause of systemic pigment induction.
      Conversely, no significant pigmentation by bacteria was observed from P.
      involutus. We found additional putative transcriptional composite elements of
      atromentin synthetase genes in P. involutus and other ectomycorrhiza-forming
      species that were absent from S. lacrymans and other brown-rotters. Variegatic
      and its precursor xerocomic acid, but not involutin, in return inhibited swarming
      and colony biofilm spreading of Bacillus subtilis, but did not kill B. subtilis.
      We suggest that dissimilar pigment regulation by fungal lifestyle was a
      consequence of pigment bioactivity and additional promoter motifs. The focus on
      basidiomycete natural product gene induction and regulation will assist in future
      studies to determine global regulators, signalling pathways and associated
      transcription factors of basidiomycetes.

PMID- 29205130
TI  - Impact of stress on the gut microbiome of free-ranging western lowland gorillas.
AB  - Exposure to stressors can negatively impact the mammalian gastrointestinal
      microbiome (GIM). Here, we used 454 pyrosequencing of 16S rRNA bacterial gene
      amplicons to evaluate the impact of physiological stress, as evidenced by faecal
      glucocorticoid metabolites (FGCM; ng/g), on the GIM composition of free-ranging
      western lowland gorillas (Gorilla gorilla gorilla). Although we found no
      relationship between GIM alpha diversity (H) and FGCM levels, we observed a
      significant relationship between the relative abundances of particular bacterial
      taxa and FGCM levels. Specifically, members of the family Anaerolineaceae
      (rho=0.4, FDR q=0.01), genus Clostridium cluster XIVb (rho=0.35, FDR q=0.02) and
      genus Oscillibacter (rho=0.35, FDR q=0.02) were positively correlated with FGCM
      levels. Thus, while exposure to stressors appears to be associated with minor
      changes in the gorilla GIM, the consequences of these changes are unknown. Our
      results may have implications for conservation biology as well as for our overall
      understanding of factors influencing the non-human primate GIM.

PMID- 29205131
TI  - Gramella antarctica sp. nov., isolated from marine surface sediment.
AB  - A Gram-stain-negative, aerobic, yellow-coloured, motile by gliding, rod-shaped
      bacterial strain, designated R17H11T, was isolated from surface sediment
      collected from the Ross Sea, Antarctica. Growth optimally occurred at 25-30 
      degrees C, at pH 7.0-7.5 and in the presence of 3 % NaCl (w/v). Phylogenetic
      trees based on 16S rRNA gene sequences indicated that strain R17H11T clustered
      together with Gramella flava JLT2011T and fell within the genus Gramella. Strain
      R17H11T shared the highest 16S rRNA gene similarities (96.1 and 96.0 %) with the
      type strains of Gramella forsetii and G. flava, and 92.6-95.5 % similarities with
      those of other known Gramella species. Strain R17H11T contained menaquinone-6 as
      the only isoprenoid quinone. The major fatty acids (>5 %) were summed feature 3
      (17.5 %, comprising C16 : 1omega7c and/or C16 : 1omega6c), iso-C15 : 0 (14.0 %),
      summed feature 9 (11.8 %, comprising 10-methyl C16 : 0 and/or iso-C17 :
      1omega9c), iso-C17 : 0 3-OH (11.8 %), iso-C16 : 0 (7.4 %), C17 : 1omega6c (6.9 %)
      and anteiso-C15 : 0 (5.1 %). The major polar lipids were
      phosphatidylethanolamine, four unidentified lipids, an unidentified aminolipid,
      an unidentified aminophospholipid and an unidentified glycolipid. The DNA G+C
      content of strain R17H11T was 38.6 mol%. On the basis of the phylogenetic,
      physiological and chemotaxonomic characteristics, strain R17H11T represents a
      novel species in the genus Gramella, for which the name Gramellaantarctica sp.
      nov. is proposed. The type strain of the novel species is R17H11T (=GDMCC
      1.1208T=KCTC 52925T).

PMID- 29205132
TI  - Stakelama algicida sp. nov., novel algicidal species of the family
      Sphingomonadaceae isolated from seawater.
AB  - We conducted a taxonomic study of two algicidal bacteria, designated strains
      Yeonmyeong 1-13T and Yeonmyeong 1-11, isolated from seawater off Geoje Island in
      the South Sea, Republic of Korea. The two novel strains were yellow-pigmented,
      halotolerant, Gram-stain-negative, strictly aerobic, non-spore-forming, rod
      shaped bacteria. Both strains were able to grow at 5-39  degrees C, pH 5.0-10.0
      and 0-11 % (w/v) NaCl concentration. Based on the 16S rRNA gene sequence
      analysis, strains Yeonmyeong 1-13T and Yeonmyeong 1-11 belonged to the genus
      Stakelama and are closely related to Stakelama pacifica JLT832T (98.37% and 98.22
      % sequence similarity, respectively). The pairwise sequence similarity between
      strains Yeonmyeong 1-13T and Yeonmyeong 1-11 was observed to be 99.50 %. In both
      strains, the only respiratory quinone was ubiquinone-10; the major polar lipids
      were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylcholine and sphingoglycolipid; the major fatty acids were C18 :
      1omega7c, C16 : 0 and C14 : 0 2-OH. DNA G+C content values of strains Yeonmyeong
      1-13T and Yeonmyeong 1-11 were 65.1% and 64.9 mol%, respectively. The DNA-DNA
      relatedness between Yeonmyeong 1-13T and S. pacifica DSM 25059T was 28.7 %, which
      falls below the threshold value of 70 % for the strain to be considered as novel.
      The morphological, physiological, chemotaxonomic and phylogenetic analyses
      clearly distinguished strain Yeonmyeong 1-13T from its closest phylogenetic
      neighbours. Thus, strains Yeonmyeong 1-13T and Yeonmyeong 1-11 represent a novel
      species of the genus Stakelama, for which the name Stakelama algicida sp. nov. is
      proposed. The type strain is Yeonmyeong 1-13T (=KEMB 9005-324T=JCM 31498T).

PMID- 29205133
TI  - Pontibacter brevis sp. nov., isolated from rhizosphere soil of Tamarix
      ramosissima.
AB  - A Gram-stain-negative, oval-shaped and light pink pigmented bacterium, designated
      XAAS-2T, was isolated from rhizosphere soil of Tamarix ramosissima. The sole
      respiratory quinone of the type strain XAAS-2T was MK-7, and the principal
      cellular fatty acids were summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1
      B) and iso-C15 : 0. The major polar lipids were phosphatidylethanolamine and two
      unidentified lipids. 16S rRNA gene sequence analysis indicated that strain XAAS
      2T belonged to the genus Pontibacter within the family Cytophagaceae with
      sequence similarities of 93.9-97.1 % to other type species of the genus
      Pontibacter and to Pontibacter xinjiangensis CCTCC AB 207200T as the closest
      neighbour. The DNA G+C content of strain XAAS-2T was 50.6 mol%. The level of DNA
      DNA relatedness of XAAS-2T and P. xinjiangensis CCTCC AB 207200T was 47.5 %
      (sd=3.27). Phenotypic and genotypic data suggested that strain XAAS-2T represents
      a novel species of the genus Pontibacter, for which the name Pontibacterbrevis
      sp. nov. is proposed, with the type strain XAAS-2T (=CCTCC AB 2016135T=JCM
      31443T).

PMID- 29205134
TI  - The C-terminal part of the human cytomegalovirus terminase subunit pUL51 is
      central for terminase complex assembly.
AB  - The cleavage and packaging of the human cytomegalovirus (HCMV) genome is
      accomplished by the viral terminase, comprising pUL56 and pUL89, and the recently
      identified pUL51 subunit. Since knowledge about pUL51 is scarce, we aimed at
      identifying pUL51 domains that are important for terminase assembly. In silico
      analysis suggested that the N-terminal half of pUL51 is intrinsically disordered,
      and that alpha-helices are present in the C-terminal part. Linker-scanning
      mutagenesis of pUL51 in the context of the viral genome revealed that amino acid
      insertions into the predicted alpha-helices are not compatible with viral growth,
      whereas upon mutagenesis of the putatively disordered parts interaction with
      pUL56 and pUL89 was retained and viral progeny was produced. Replacement of pUL51
      with the closely related M51 protein of mouse cytomegalovirus did not lead to
      viable virus, indicating that M51 cannot substitute for pUL51, and swapping the
      M51 and UL51 N- and C-termini demonstrated the critical role of the pUL51 C
      terminal part in building the terminase complex. Notably, the pUL51 C-terminus
      alone turned out to be sufficient to enable terminase assembly, its nuclear
      localization and plaque formation. Using HCMV mutants expressing differently
      tagged pUL51 versions, we did not detect oligomerization of pUL51, as has been
      proposed for the pUL51 orthologues of other herpesviruses. These data provide an
      insight into the interaction of pUL51 with the other two terminase components,
      and provide the basis for unravelling the mode of action of novel antiviral drugs
      targeting the HCMV terminase.

PMID- 29205135
TI  - A hemin auxotrophic Enterobacter cloacae clinical isolate with increased
      resistance to carbapenems and aminoglycosides.
AB  - Small-colony variants (SCVs) were obtained from an Enterobacter cloacae clinical
      isolate in Okinawa, Japan. One variant showed auxotrophy for hemin with a
      deletion of 20 365 nucleotides, dosC-ydiK-mmuP-mmuM-tauA-tauB-tauC-tauD-hemB-yaiT
      yaiV-ampH-yddQ-sbmA-yaiW-yaiY-yaiZ, including hemB, and was more resistant to
      aminoglycosides and carbapenems, but more susceptible to aztreonam, than the
      parent strain.

PMID- 29205136
TI  - Vicingus serpentipes gen. nov., sp. nov., a new member of the Flavobacteriales
      from the North Sea.
AB  - A new member of the Flavobacteriales was isolated from the surface of a stone
      collected on the German North Sea shore. The bacterium, strain ANORD5T, is a
      mesophilic, chemoheterotrophic aerobic, typical marine bacterium. Optimal growth
      was observed at 20-30  degrees C, pH 7.0-8.5 and 1-2 % sea salt. The 16S rRNA
      gene sequence revealed a distant relationship with the representatives of the
      Cryomorphaceae, with less than 90 % sequence similarity. Strain ANORD5T forms a
      cluster together with Owenweeksia hongkongensis UST20020801T (89.9 %), Cryomorpha
      ignava 1-22T (87.9 %), Luteibaculum oceani CC-AMWY-103BT (88.1 %) and
      Phaeocystidibacter luteus PG2S01T (87.3 %). Strain ANORD5T has a low DNA G+C
      content (31 mol%). Based on morphological, physiological and phylogenetic data,
      strain ANORD5T is considered a type strain of a new species and a new genus of
      the family Cryomorphaceae for which the name Vicingus serpentipes is proposed.
      The type strain is ANORD5T (=NCIMB 15042T=DSM 103558T=MTCC 12686T).

PMID- 29205137
TI  - Maribius pontilimi sp. nov., isolated from a tidal mudflat.
AB  - A novel marine Gram-negative bacterium, designated strain GH1-23T, was isolated
      from a tidal mudflat sample collected at Dongmak seashore on Gangwha Island,
      Republic of Korea and its taxonomic position was determined through a polyphasic
      investigation. The bacterium was strictly aerobic, chemoheterotrophic, catalase-
      and oxidase-positive, consisted of non-motile rods and grew optimally at 30 
      degrees C, pH 7 and 1 % NaCl. The predominant cellular fatty acids were C18 :
      1omega7c and cyclo-C19 : 0omega8c. The major isoprenoid quinone was Q-10. The
      major polar lipids were phosphatidylglycerol, a phosphoglycolipid and an
      aminolipid. Comparative 16S rRNA gene sequence analysis revealed that the isolate
      was closely related to members of the genus Maribius. The highest 16S rRNA gene
      sequence similarity was found to be 97.5 % to Maribius salinus followed by 97.4 %
      to Maribius pelagius; levels of 16S rRNA gene sequence similarity between the
      novel strain and other representatives of family Rhodobacteraceae were <95.5 %.
      The DNA G+C content was 66.7 mol % and DNA-DNA relatedness values with the type
      strains of species of the genus Maribius were 33-39 %. Based on combined data
      from a polyphasic investigation, strain GH1-23T (=KCTC 52957T=DSM 104950T)
      represents a novel species of the genus Maribius, for which the name Maribius
      pontilimi sp. nov. is proposed.

PMID- 29205138
TI  - Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016,
      including among carbapenemase gene-positive hypervirulent K1-ST23 and 'non
      hypervirulent' types ST147, ST15 and ST383.
AB  - PURPOSE: Klebsiella pneumoniae is a concern because of its multidrug resistance
      and the ability of hypervirulent types, especially capsular type K1-clonal
      complex 23 (K1-CC23), to cause community-acquired, life-threatening infections.
      Hypervirulent types carry an array of virulence genes including rmpA/rmpA2,
      coding for capsule up-regulation. We sought to identify isolates carrying these
      elements among submissions to the UK national reference laboratory during 2016.
      METHODOLOGY: Virulence elements and carbapenemase genes were sought by PCR or
      from whole genome sequences. Isolates were typed by variable number tandem repeat
      analysis or by multi locus sequence typing from whole genome sequences. Long read
      nanopore sequencing was carried out on two isolates.Results/Key findings. Twelve
      of 1090 isolates (1.1 %) belonged to hypervirulent K1-CC23, with one carrying
      blaOXA-48 (KpvST23L_OXA-48). A further 24 rmpA/rmpA2-positive isolates were
      detected: eight belonged to hypervirulent types of capsular types K2 and K54; and
      14 belonged to 'non-hypervirulent' ST147, ST15 and ST383 and also carried
      carbapenemase gene(s). Virulence, heavy metal and antibiotic resistance gene
      contents were compared from whole genome sequences of KpvST23L_OXA-48 and one of
      the ST147 isolates carrying blaNDM-1. They carried 94/96 and 26/96 of the
      virulence genes sought, and 23/23 and 9/23 of the heavy metal resistance genes,
      respectively. In the ST147 isolate, rmpA/rmpA2 and the aerobactin siderophore
      cluster were on a large virulence plasmid together with resistance genes. The
      yersiniabactin cluster was widely present among carbapenemase gene-positive
      isolates, including among those that were rmpA/rmpA2-negative. CONCLUSION: Our
      results highlight a combination of virulence and resistance genes, which could
      lead to untreatable invasive infections.

PMID- 29205139
TI  - A neurological disease on the face of an ancient Roman sculpture.

PMID- 29205140
TI  - Autologous fat transplantation for secondary breast reconstruction: our
      experience.
AB  - BACKGROUND: Autologous fat transplantation is used after breast reconstruction to
      improve the breast profile. There are a variety of different methods used for fat
      harvesting, preparation, and reinjection. This study describes the specific
      techniques we used in this series of autologous fat transplantations in breast
      reconstruction patients and reports their outcomes compared with other studies in
      the literature. PATIENTS AND METHODS: At the University Hospital of Parma between
      May 2012 and December 2016, we performed 53 autologous fat transplantations for
      secondary breast reconstruction patients with an average age of 49 years (range:
      34-65 y). A tumescent fluid (NaCl, epinephrine, and a local anaesthetic) was
      injected, and the lipoaspirate was harvested using a closed aspiration-injection
      system connected to a 50 ml syringe, a 4 mm infiltration cannula, and a -650 mmHg
      vacuum. The average amount of lipoaspirate obtained was 100 ml (range: 50-200
      ml). Centrifugation of the lipoaspirate (3000 rpm for 3 min) was performed to
      isolate the adipose tissue (average amount obtained, 80 ml; range: 30-180 ml).
      Under local anaesthesia, the retrograde injection of thin layers of fat graft in
      multiple tunnels was performed in the subcutaneous and/or subglandular planes.
      RESULTS: Average follow-up was six months. Comparable to other studies, our
      complication rate was 7.4% (n = 4/53) and included cyst formation at the
      injection site (n = 1/53) and hematoma at the donor site (n = 3/53). Repeat fat
      grafting was performed in 28.3% of patients (n = 15/53) due to fat graft
      resorption. CONCLUSIONS: Autologous fat transplantation is a useful procedure for
      correcting irregularities in the breast contour in secondary breast
      reconstruction.

PMID- 29205141
TI  - Deep spinal infection in instrumented spinal surgery: diagnostic factors and
      therapy.
AB  - AIM: Postoperative surgical site infections (SSI) are complication of spinal
      surgery. These complications may lead to a poor outcome with neurological
      deficits, spinal deformity and chronic pain. The purpose of this study is to
      explore the statistical value of diagnostic parameters and the proper therapy.
      METHOD: We retrospectively reviewed 550 patients who underwent spinal
      instrumentation at our department from January 2011 to December 2015. The SSI was
      present in 16 patients out of 550 operated. Diagnostic criteria of SSI were the
      positivity of the surgical wound swab or blood culture, the clinical findings,
      positivity of laboratory tests and radiological elements. All patients had peri
      operative antibiotic prophylaxis. Diagnostic laboratory findings were compared
      with a homogeneous control group of 16 patients and analyzed by univariate
      statistical analysis with Chi-square test for the discrete variables. P<0,05 was
      considered statistically significant. RESULTS: Matching the SSI patients with a
      group of control, fever was not statistically significant for diagnosis as number
      of leukocytes, neutrophils and lymphocytes. On the contrary values of ESR and CRP
      were statistically significant with p <0, 01. The hardware was removed only in 3
      patients (18%) out of 16 SSI patients. CONCLUSION: In this study the
      statistically significant parameters to diagnose SSI are ESR and CRP values. The
      leucocytes count, number of lymphocytes and presence of fever integrates the data
      of ESR and CRP with no statistical significance. Most patients with SSI reach
      clinical healing with favorable outcome by means of target antibiotic therapy
      without hardware removal.

PMID- 29205142
TI  - Necrotizing fasciitis associated with primary cutaneous B-cell lymphoma. A case
      report.
AB  - : Necrotizing fasciitis is a rapidly progressive and life-threatening infection
      of the deeper skin layers and subcutaneous tissues that moves along the facial
      planes. OBJECTIVES: We present the rare case of a patient with necrotizing
      fasciitis associated with high malignancy b-cell lymphoma. Our purpose is to
      investigate the probable connection between the two pathologies and evaluate the
      importance of early surgical intervention. CASE REPORT: 51-year old Caucasian
      woman presented at the E.R. with history of a painful left thigh over a week and
      fever up to 38,4 degrees C over the last three days. Necrosis of the soft tissues
      and fascial planes were observed clinically. After the initial treatment and due
      to the patient's multiple organ dysfunction (septic shock), she was transferred
      to the ICU were she was intubated resuscitated with IV fluids and given IV
      antibiotics. 24 hours after the admission it was decided that the patient should
      undergo surgery and an extensive debridement of the necrotic area was performed.
      The antibiogram of the blood culture revealed streptococcus pyogenes and she was
      administered penicillin while intubated and monitored in the ICU until the
      seventh postoperative day. On the eighth post-day she was transferred back to the
      surgical department, hemodynamically normal and stable. She was discharged one
      month later and she was referred to a plastic surgery center for the final
      reconstruction surgery. CONCLUSIONS: This case highlights that the high index of
      suspicion and the early aggressive surgical intervention seems to be very
      critical to improve survival of the patients with necrotizing fasciitis.

PMID- 29205143
TI  - Epidural abscess imitating recurrent pilonidal sinus: a case report.
AB  - Pilonidal sinus or pilonidal cyst is a common benign disease, affecting mostly
      young working men. We present the first case of an epidural abscess imitating
      pilonidal sinus. A 33-year old male, suffering from previously undiagnosed and
      untreated diabetes mellitus (DM), presented to our emergency department (ER), one
      month after open surgical treatment of pilonidal sinus, due to weakness and
      fever. After re-operation of the pilonidal cyst and due to post-operative pus
      production and continuation of fever a computer tomogr aphy (CT )scan was
      performed revealing an epidural abscess extending from the thoracic vertebrae 12
      (T-12) to the sacrococcygeal area. At that point he underwent new surgery for
      drainage of the epidural abscess. The patient received intravenous antimicrobial
      treatment and was discharged on the 23rd postoperative day without signs or
      symptoms of infection. At follow up for a whole year no signs of recurrence have
      been observed.

PMID- 29205144
TI  - Primitive squamous cell carcinoma of the breast (SCCB): case report of an
      uncommon variant of metaplastic carcinoma.
AB  - INTRODUCTION: Metaplastic carcinoma of the breast includes a heterogeneous group
      of neoplasms characterized by admixture of adenocarcinoma with area of squamous,
      chondroid and osseous differentiation. If the tumor shows pure squamous
      differentiation, it is designated as squamous carcinoma. SCCB accounts for less
      than 1% of all invasive breast carcinoma. It can present as cystic lesions and
      simulate a breast abscess. CASE REPORT: A 75-year old woman was visited at our
      General Surgery Unit for a palpable lump, about 5 cm in size, at the lower inner
      quadrant of right breast. Mammography revealed 3cm oval opacity with micro
      calcifications and US appearance as isoechogenic lump with lesion solid-cystic
      appearance; cytology deposes for cystic inflammatory lesion(C2) to be monitored.
      A subsequent ultrasound check one year later confirmed an increase of volume, so
      micro histology sampling was made with suspect malignancy(B4). After biopsy, the
      patient underwent excision of cyst. Final histological examination showed SCCB
      with diffuse positivity for Cytokeratin 34beta-E12 and p63; negative reactions to
      ER and PR; monoclonal antibody Ki67 > 40%; HER2/neu with score 2+ and FISH
      examination negative. Subsequently, the patient underwent radical Madden
      mastectomy which confirmed the histological diagnosis and the negativity of the
      lymph nodes. DISCUSSION: In literature, prognosis and therapy are still
      discussed; SCCB has shown very little responsiveness to common chemotherapy.
      CONCLUSION: A quadrantectomy or a radical mastectomy with lymph node dissection
      must be considered the best treatment for this rare neoplasia.

PMID- 29205145
TI  - Polythelia in a 13-year old girl.
AB  - We present a rare case of a 13-year old girl with a bilateral polythelia. We
      would like to draw attention to this particular mammary malformation.

PMID- 29205146
TI  - Primary intestinal choriocarcinoma in a patient with long-standing Crohn's
      disease.
AB  - Extra-gonadal choriocarcinoma is an extremely rare highly malignant neoplasm with
      a poor prognosis. In the gastrointestinal tract it usually arises in stomach,
      esophagous, bowel intestine and colon. Only few cases are pure and not associated
      with a classic adenocarcinoma. The correlation of Crohn's disease with
      choriocarcinoma is not reported. We describe a case of 47-year old man with
      primary choriocarcinoma of the colon in a previously documented Crohn's disease.

PMID- 29205148
TI  - ATLAS OF ANATOMY, Latin nomenclature (3rd edition).

PMID- 29205147
TI  - Medico legal aspects on neuromonitoring in thyroid surgery: informed consent on
      malpractice claims.
AB  - AIM: The purpose of this paper is to provide a forensic profile framework of
      neuromonitoring in thyroid surgery, regarding the information given to the
      patient and its classification as part of professional liability in the event of
      recurrent injury. METHOD: Evaluation and reflections on the required behaviour of
      the surgeon on providing details on the operation before the informed consent is
      given and to outline the possible legal implications regarding professional
      liability as a result of recurrent injury. In particular, if it is an obligation
      to inform the patient about using this method and if it is possible for the
      surgeon to freely choose whether to employ this method, which is still burdened
      by a certain percentage of error and for that reason it cannot be defined a
      "standard of care". RESULTS: To recognize neuromonitoring the role of standard of
      care in surgery of the thyroid means attribute a role of method able to avoid the
      surgeon to cause iatrogenic damage to the laryngeal nerve. For the foregoing
      reasons that is not true, determining false positives and false negatives, and
      this can be a double edged sword for the surgeon. CONCLUSIONS: Although the
      progress in the field of thyroid surgery made in the last decade, currently there
      is no scientific reassuring evidence to completely avoid the possibility of
      producing an iatrogenic lesion of the laryngeal nerve. Information given to the
      patient prior to surgery should respect the requirements of completeness, freedom
      and honesty in order to allow the patient to self-determination.

PMID- 29205149
TI  - III CONGRESSO NAZIONALE S.I.C.U.T. DI PRIMAVERA La Chirurgia d'Urgenza e del
      Trauma Italiana nei contesti di maxiemergenza.

PMID- 29205150
TI  - A pragmatic multicentre randomised controlled trial comparing stapled
      haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease:
      the eTHoS study.
AB  - BACKGROUND: Haemorrhoids are a benign anorectal condition and are highly
      prevalent in the UK population. Treatments involve clinic-based procedures and
      surgery. The surgical procedures available include stapled haemorrhoidopexy (SH)
      and traditional haemorrhoidectomy (TH), and over 25,000 operations are performed
      for haemorrhoids annually in the UK. The disease is therefore important both to
      patients and to health service commissioners. Debate remains as to which of these
      surgical procedures is the most clinically effective and cost-effective.
      OBJECTIVE: The aim of this study was to compare the clinical effectiveness and
      cost-effectiveness of SH with that of TH. DESIGN: A large, open two-arm parallel
      group pragmatic multicentre randomised controlled trial involving 32 UK hospitals
      and a within-trial cost-benefit analysis. A discrete choice experiment was
      conducted to estimate benefits (willingness to pay). PARTICIPANTS: Patients with
      grades II-IV haemorrhoids who had not previously undergone SH or TH were included
      in the study. INTERVENTIONS: Participants were randomised to receive either SH or
      TH. Randomisation was minimised at 1 : 1, in accordance with baseline EuroQol-5
      Dimensions, three-level version (EQ-5D-3L) score, haemorrhoid grade, sex and
      centre, via an automated system. MAIN OUTCOME MEASURES: The primary outcome was
      area under the quality-of-life curve measured using the EQ-5D-3L descriptive
      system over 24 months, and the primary economic outcome was the incremental cost
      effectiveness ratio. Secondary outcomes included disease-specific quality of
      life, recurrence, complications, further interventions and costs. RESULTS:
      Between January 2011 and August 2014, 777 patients were randomised (389 to
      receive SH and 388 to receive TH). There were 774 participants included in the
      analysis as a result of one post-randomisation exclusion in the SH arm and two in
      the TH arm. SH was less painful than TH in the short term. Surgical complications
      were similar in both arms. EQ-5D-3L score was higher for the SH arm in the first
      6 weeks after surgery, but over 24 months the TH group had significantly better
      EQ-5D-3L scores (-0.073, 95% confidence interval -0.140 to -0.006; p = 0.0342).
      Symptoms and further interventions were significantly fewer in the TH arm at 24
      months. Continence was better in the TH arm and tenesmus occurred less
      frequently. The number of serious adverse events reported was 24 out of 337
      (7.1%) for participants who received SH and 33 out of 352 (9.4%) for those who
      received TH. There were two deaths in the SH arm, both unrelated to the eTHoS
      (either Traditional Haemorrhoidectomy or Stapled haemorrhoidopexy for
      haemorrhoidal disease) study. Patient preference did not seem to influence the
      treatment difference. SH was dominated by TH as it cost more and was less
      effective. The net benefit for the TH arm was higher than that for the SH arm.
      LIMITATIONS: Neither the participants nor the assessors were masked to treatment
      assignment and final recruitment was slightly short of the total target of 800.
      There were also substantial missing follow-up data. CONCLUSIONS: While patients
      who received SH had less short-term pain, after 6 weeks, recurrence rates,
      symptoms, re-interventions and quality-of-life measures all favoured TH. In
      addition, TH is cheaper. As part of a tailored management plan for haemorrhoids,
      TH should be considered over SH as the surgical treatment of choice for
      haemorrhoids refractory to clinic-based interventions. FUTURE WORK: Perform an
      updated meta-analysis incorporating recently conducted European trials [eTHoS,
      HubBLe (haemorrhoidal artery ligation versus rubber band ligation for the
      management of symptomatic second-degree and third-degree haemorrhoids) and
      LingaLongo (Cost-effectiveness of New Surgical Treatments for Haemorrhoidal
      Disease)]. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80061723. FUNDING:
      This project was funded by the National Institute for Health Research (NIHR)
      Health Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 21, No. 70. See the NIHR Journals Library website for
      further project information.

PMID- 29205152
TI  - Branching into brains.
AB  - What can artificial intelligence learn from neuroscience, and vice versa?

PMID- 29205151
TI  - Towards deep learning with segregated dendrites.
AB  - Deep learning has led to significant advances in artificial intelligence, in
      part, by adopting strategies motivated by neurophysiology. However, it is unclear
      whether deep learning could occur in the real brain. Here, we show that a deep
      learning algorithm that utilizes multi-compartment neurons might help us to
      understand how the neocortex optimizes cost functions. Like neocortical pyramidal
      neurons, neurons in our model receive sensory information and higher-order
      feedback in electrotonically segregated compartments. Thanks to this segregation,
      neurons in different layers of the network can coordinate synaptic weight
      updates. As a result, the network learns to categorize images better than a
      single layer network. Furthermore, we show that our algorithm takes advantage of
      multilayer architectures to identify useful higher-order representations-the
      hallmark of deep learning. This work demonstrates that deep learning can be
      achieved using segregated dendritic compartments, which may help to explain the
      morphology of neocortical pyramidal neurons.

PMID- 29205153
TI  - An Aedes aegypti-associated fungus increases susceptibility to dengue virus by
      modulating gut trypsin activity.
AB  - Transmission of dengue virus (DENV) requires successful completion of the
      infection cycle in the Aedes aegypti vector, which is initiated in the midgut
      tissue after ingestion of an infectious blood meal. While certain Ae. aegypti
      midgut-associated bacteria influence virus infection, little is known about the
      midgut-associated fungi (mycobiota), and how its members might influence
      susceptibility to DENV infection. We show that a Talaromyces (Tsp_PR) fungus,
      isolated from field-caught Ae. aegypti, render the mosquito more permissive to
      DENV infection. This modulation is attributed to a profound down-regulation of
      digestive enzyme genes and trypsin activity, upon exposure to Tsp_PR-secreted
      factors. In conclusion, we show for the first time that a natural mosquito gut
      associated fungus can alter Ae. aegypti physiology in a way that facilitates
      pathogen infection.

PMID- 29205156
TI  - Edge-to-edge repair of a large anterior leaflet notch with severe tricuspid
      regurgitation.

PMID- 29205154
TI  - Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory
      genetic variation influencing height.
AB  - GWAS have identified hundreds of height-associated loci. However, determining
      causal mechanisms is challenging, especially since height-relevant tissues (e.g.
      growth plates) are difficult to study. To uncover mechanisms by which height GWAS
      variants function, we performed epigenetic profiling of murine femoral growth
      plates. The profiled open chromatin regions recapitulate known chondrocyte and
      skeletal biology, are enriched at height GWAS loci, particularly near
      differentially expressed growth plate genes, and enriched for binding motifs of
      transcription factors with roles in chondrocyte biology. At specific loci, our
      analyses identified compelling mechanisms for GWAS variants. For example, at
      CHSY1, we identified a candidate causal variant (rs9920291) overlapping an open
      chromatin region. Reporter assays demonstrated that rs9920291 shows allelic
      regulatory activity, and CRISPR/Cas9 targeting of human chondrocytes demonstrates
      that the region regulates CHSY1 expression. Thus, integrating biologically
      relevant epigenetic information (here, from growth plates) with genetic
      association results can identify biological mechanisms important for human
      growth.

PMID- 29205155
TI  - Hedgehog signaling via Gli2 prevents obesity induced by high-fat diet in adult
      mice.
AB  - Obesity poses a significant risk of developing type II diabetes and other
      diseases. Hedgehog (Hh) signaling has been shown to inhibit adipose tissue
      development, but its effect on diet-induced obesity during postnatal life is not
      known. Here by inducing expression of constitutively active Smoothened (SmoM2) or
      Gli2 (DeltaNGli2) in the adipocyte lineage of postnatal mice, we show that
      targeted activation of Hh signaling suppresses high-fat-diet-induced obesity and
      improves whole-body glucose tolerance and insulin sensitivity. Both SmoM2 and
      DeltaNGli2 induce the expression of Wnt6, a known anti-adipogenic factor, in fat
      depots of the mouse. Hh-Gli2 signaling inhibits not only adipocyte
      differentiation but also lipogenesis in adipocytes in vitro. Finally,
      pharmacological inhibition of Porcupine, an acyltransferase essential for Wnt
      secretion, alleviates both anti-adipogenic and anti-lipogenic effects of Hh in
      cell culture models. Overall, targeted activation of Hh signaling ameliorates
      diet-induced obesity and may be explored for pharmaceutical development.

PMID- 29205157
TI  - A comparison of an ultrathin-strut biodegradable polymer sirolimus-eluting stent
      with a durable polymer everolimus-eluting stent for patients with acute ST
      segment elevation myocardial infarction undergoing primary percutaneous coronary
      intervention: rationale and design of the BIOSTEMI trial.
AB  - AIMS: A novel ultrathin-strut biodegradable polymer sirolimus-eluting stent (BP
      SES) (Orsiro; Biotronik, Bulach, Switzerland) was shown to be superior to a thin
      strut durable polymer everolimus-eluting stent (DP-EES) (XIENCE Xpedition/Alpine;
      Abbott Vascular, Santa Clara, CA, USA) with respect to the primary endpoint of
      target lesion failure (TLF) at 12 months in the pre-specified subgroup of
      patients with ST-segment elevation myocardial infarction (STEMI) included in the
      BIOSCIENCE trial. We designed a large-scale, randomised, clinical trial to assess
      the clinical superiority of ultrathin-strut BP-SES over thin-strut DP-EES among
      patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).
      METHODS AND RESULTS: BIOSTEMI (NCT02579031) is a prospective, multicentre,
      randomised, controlled, superiority trial that will randomly assign 1,250
      patients with STEMI undergoing PPCI to treatment with BP-SES or DP-EES. The
      primary endpoint of TLF, a composite of cardiac death, target vessel
      reinfarction, and clinically indicated target lesion revascularisation within 12
      months, will be analysed with Bayesian models applied to the BIOSTEMI data set
      (n=1,250) using robust historical priors to incorporate historical information
      from the BIOSCIENCE STEMI subgroup (n=407). CONCLUSIONS: The BIOSTEMI trial will
      determine whether ultrathin-strut BP-SES are superior to thin-strut DP-EES with
      respect to TLF in patients with STEMI undergoing PPCI.

PMID- 29205158
TI  - Prognostic impact of non-culprit chronic total occlusions in infarct-related
      cardiogenic shock: results of the randomised IABP-SHOCK II trial.
AB  - AIMS: The aim of the current study was to investigate the impact of a chronic
      total occlusion (CTO) in a non-infarct-related coronary artery (non-IRA) on one
      year mortality and occurrence of cardiac arrhythmia in patients with cardiogenic
      shock (CS) complicating acute myocardial infarction (AMI). METHODS AND RESULTS:
      In a retrospective sub-analysis of the Intraaortic Balloon Pump in Cardiogenic
      Shock II trial (IABP-SHOCK II) and its accompanying registry, 201 (26%) of 761
      patients had a CTO in a non-IR major coronary artery. Mortality was significantly
      higher in the CTO group at day of admission (19% vs. 11%; p=0.005), 30 days (53%
      vs. 41%, p=0.002), and 12 months (63% vs. 51%, p=0.002). In the adjusted
      multivariate Cox regression analysis, a CTO in a non-IRA was an independent
      predictor of mortality at 12 months (hazard ratio 1.30, 95% confidence interval
      [CI]: 1.02-1.67, p=0.03). At 30-day follow-up, ventricular arrhythmias requiring
      defibrillation occurred more frequently in patients with non-IRA CTO in the
      univariate analysis (33% vs. 21%, odds ratio 1.83, 95% CI: 1.28-2.62, p=0.002).
      CONCLUSIONS: In patients with CS complicating AMI, the presence of CTO in a non
      IRA is associated with a higher incidence of ventricular arrhythmias and is an
      independent predictor of mortality at 12-month follow-up.

PMID- 29205159
TI  - [Experience with third, fourth and fifth kidney transplants and their
      complications.]
AB  - OBJECTIVES: Kidney transplant may be a good choice to treat chronic renal failure
      even in patients with two or more previous renal grafts. However, there might be
      several surgical complications and other difficulties we have to deal with. The
      aim of this report is to analyze the third, fourth and fifth transplants
      performed in our center focusing on the surgical complications and graft and
      patient survivals. METHODS: We performed a retrospective analysis of the 73
      third, fourth and fifth kidney transplants performed in our center between
      February 1975 and December 2015. Statistical analysis has been performed with IBM
      SPSS 23.0 software. RESULTS: 62 patients received a third graft, 10 received a
      fourth one and one patient received a fifth graft. The median age of the
      recipients was 48 years, while for donors it was 50. Median cold ischemia time
      was 21 hours. Transplantectomy was not necessary in 49.31% of the cases. In 59.7%
      of the cases the graft vessels were anastomosed to the external iliac vessels.
      There were 21 cases of relevant postoperative complications (27.4% of the total
      grafts). Vascular thrombosis appeared in 5.5%. After 49 months of follow-up, the
      1-, 3-, and 5-year graft survival were 64.3%, 56.16% and 50.69%, respectively.
      CONCLUSIONS: A new renal transplant in patients with two or more previous grafts
      is feasible, being necessary to individualize the cases. In spite of being more
      complex operations than previous transplants with a higher complication rate, we
      can obtain both acceptable graft and patient survival outcomes with an
      appropriate approach.

PMID- 29205160
TI  - Glans penis phimosis in antiquity as depicted upon two roman ex-votos.

PMID- 29205161
TI  - [Low dose rate brachytherapy in low and middle risk prostate cancer: Results and
      impact on quality of life with 5 year follow up.]
AB  - Low dose rate brachytherapy (LDR-Br) with radioactive isotopes is a curative
      treatment and has shown to be comparable for the management of localized prostate
      cancer (PCa) to more conventional treatments such as radical prostatectomy or
      external beam radiotherapy, but with fewer side effects. The aim of this study is
      to show the global, specific and biochemical recurrence-free survival in 193
      patients undergoing low dose rate Brachytherapy with permanent implants with
      iodine 125 and analyze the quality of life impact. 193 patients with localized
      PCa were consecutively treated over a period of 10 years (2005-2015). All of them
      were followed up on levels of prostate specific antigen (PSA) and 68 of them
      completed a quality of life survey. The average age was 62.8 years and the
      average PSA was 6.4 ng/dl at the time of Br. 29.5% of patients were classified as
      intermediate risk, with a Gleason score sum of 7 and/or a PSA between 10 and 20
      ng/dl. Mean follow-up was 64.2 months; overall, specific and biochemical
      recurrence-free survival were 92.8%, 99.0% and 90.2% respectively. The most
      significant changes in the quality of life recorded were urinary incontinence,
      urinary and bowel irritative symptoms, in the first 6 months after brachytherapy.
      Sexual function shows significant changes but all with favorable response using
      phosphodiesterase inhibitors. This series of patients with PCa shows similar
      biochemical free survival rates BFSR in low risk patients to external beam
      radiotherapy and radical prostatectomy, but better BFSR in intermediate risk
      patients. The impact in the quality of life was significant in urinary
      incontinence, urinary irritate symptoms, and sexual function, but they were
      transitory with the exception of sexual function.

PMID- 29205162
TI  - Multiparametric-MRI-Guided Biopsy in the Era of Precision Medicine.
AB  - OBJECTIVE: Technical improvements in prostate magnetic resonance imaging (MRI)
      have resulted in the use of MRI to target prostate biopsy. This allowed
      urologists to progress from blind biopsies to target biopsies with a better
      performance in prostate cancer (PC) diagnosis. We herein review the current
      status of Magnetic Resonance Imaging Guided Biopsy (MRGB) for the detection of
      PC. METHODS: A systematic review of the literature was conducted using PubMed,
      Embase and Cochrane using the search criteria: "PC and MRI/US fusion" or "PC and
      guided biopsy" or "PC and multiparametric MRI" or "PC and MRI guided prostate
      biopsy". Four reviewers coindependently assessed 8228 records and 38 records
      directly comparing MRGB with transrectal ultrasoundguided biopsy (TRUS) were
      chosen. However, a risk bias assessment was not performed. RESULTS: In naive
      patients, MRGB detected similar PC (51% vs 47.5%) than TRUS, more significant PC
      (SPC [41% vs 33%]) and less not significant PC (NSPC [7.7% vs 14.5%]) with less
      number of biopsies. In patients with previous negative prostate biopsy MRGB
      detected more PC (46.3% vs 26.6%), more SPC (32 % vs 16%) and less NSPC (9.5% vs
      14.5%) than TRUS, with less number of biopsies. Besides, in previous biopsy
      patients group MRGB is better at detecting anterior PC than TRUS. CONCLUSION:
      MRGB increased PC detection in patients with previous biopsies and also increased
      SPC detection at the expense of decreasing NSPC detection in both groups of
      patients with fewer biopsies when compared with TRUS. These results demonstrate
      the value of MRGB in PC diagnosis.

PMID- 29205163
TI  - Extramedullary plasmacytoma of the testicle.
AB  - OBJECTIVE: We present the case of a patient diagnosed with a testicular
      extramedullary plasmacytoma (EMP), and perform a brief review of the literature
      of this pathology. METHODS: A 64 year-old male patient, with history of multiple
      myeloma successfully treated three years before, presented with left testicular
      swelling. Initial work-up was compatible with a testicular tumor and radical
      inguinal orchiectomy was performed. RESULTS: Histologic examination of the testis
      revealed extensive intertubular infiltration by CD138 and CD56 atypical plasma
      cells, with diffuse staining for IgA, compatible with EMP. CONCLUSIONS: Invasion
      of the testis in multiple myeloma patients as a recurrence of the disease is an
      extremely rare condition, as EMPs are more common in other organ systems. Initial
      treatment should be the same as a primary testicular tumor with radical inguinal
      orchiectomy, and definitive diagnosis is established in histologic analysis.

PMID- 29205164
TI  - Genital reconstruction with IntegraTM artificial dermis after radical resection
      in a boy with diffuse lymphangiomatosis.
AB  - OBJECTIVE: Lymphangiomatosis is a rare disease affecting lymphatic vessels that
      causes a marked increase of them in the affected area. The final objective of
      treatment of the genital disease is to preserve sexual function and voiding with
      a satisfactory aesthetic result with the aim to minimize the emotional impact.
      METHODS: For the first time in children, we report a case of local reconstruction
      using artificial dermis after the excision of a genital lymphatic malformation in
      an eight year old patient. RESULTS: We performed surgical excision of the
      lymphatic malformation genital component and reconstruction of the scrotal and
      penile area in two steps, using an autologous graft over artificial dermis. No
      complications were registered. Both aesthetic and functional results were
      excellent, and spontaneous erections that were not present before, were also
      evidenced. No local recurrence was seen at two year follow up. CONCLUSION: The
      use of artificial dermis for genital surface reconstruction enables radical
      excision of tissues involved by diffuse lymphangiomatosis in this location.
      Surgical technique is simple, postoperative care is easy, being ambulatory care
      feasible. Final result is an elastic, fine skin, very satisfactory aesthetically,
      and functionally normal, which even keeps local sensitivity. In the long term,
      this will benefit the sexual field, so damaged in this patients.

PMID- 29205165
TI  - Prevalence of antibiotic resistance in fecal flora before transrectal ultrasound
      guided prostate biopsy and the clinical impact of targeted antibiotic
      prophylaxis.
AB  - OBJECTIVES: In this study, we aimed to evaluate ciprofloxacin resistance and the
      presence of extended-spectrum beta-lactamase producing organisms (ESBLs) in the
      population of patients with indication to undergo prostate biopsy. Our additional
      aim was to compare the targeted antibiotic prophylaxis and sepsis rates after
      transrectal ultrasound guided prostate biopsy in patients who received routine
      ciprofloxacin prophylaxis and to evaluate the predictive factors of antibiotic
      resistance. METHODS: Between September 2012 and January 2014, 300 patients were
      randomized to two groups. The first group (Group 1, n=156) received routine
      ciprofloxacin prophylaxis and the second group (Group 2, n=144) received a
      targeted prophylactic antibiotic regime that was adequate for rectal swab culture
      results. Rectal swab cultures were collected two weeks before the procedure.
      After the procedure, patients were followed for one month and told to return to
      the hospital if they developed a fever (>38 degrees C), shivering, dysuria or
      fatigue. RESULTS: In Group 1, four patients (2.6%) returned to our clinic with
      signs of sepsis; no patient in Group 2 returned to our clinic (p= 0.124). When
      the rectal swab culture results of Group 2 were evaluated, there were ESBLs in 18
      patients (12.5%), quinolone resistance in 26 patients (18%), and both ESBLs and
      quinolone resistance in 15 patients (10.4%). There were no statistically
      significant differences between antibiotic resistance and urologic operations,
      urinary tract infections, prior catheterization history, the presence of a
      catheter during prostate biopsy and antibiotic usage history due to a high PSA
      level. CONCLUSION: In our study, the rates of ESBL presence and ciprofloxacin
      resistance in rectal flora were not negligible. However, by obtaining rectal swab
      cultures prior to performing transrectal prostate biopsies and using targeted
      prophylaxis before prostate biopsy, the sepsis rates were reduced; however, this
      effect was statistically insignificant. Additional studies with a larger patient
      population could help to evaluate the targeted prophylaxis procedure.

PMID- 29205166
TI  - Obstructive uropathy due to double J catheter bending.

PMID- 29205167
TI  - Persistent renal colic due to a ureteral stone in a bilateral double ureteral
      system.

PMID- 29205168
TI  - Effect of static scatterers in laser speckle contrast imaging: an experimental
      study on correlation and contrast.
AB  - Laser speckle contrast imaging (LSCI) is a non-invasive microvascular blood flow
      assessment technique with good temporal and spatial resolution. Most LSCI
      systems, including commercial devices, can perform only qualitative blood flow
      evaluation, which is a major limitation of this technique. There are several
      factors that prevent the utilization of LSCI as a quantitative technique. Among
      these factors, we can highlight the effect of static scatterers. The goal of this
      work was to study the influence of differences in static and dynamic scatterer
      concentration on laser speckle correlation and contrast. In order to achieve
      this, a laser speckle prototype was developed and tested using an optical phantom
      with various concentrations of static and dynamic scatterers. It was found that
      the laser speckle correlation could be used to estimate the relative
      concentration of static/dynamic scatterers within a sample. Moreover, the speckle
      correlation proved to be independent of the dynamic scatterer velocity, which is
      a fundamental characteristic to be used in contrast correction.

PMID- 29205169
TI  - Potential for thermal damage to the blood-brain barrier during craniotomy:
      implications for intracortical recording microelectrodes.
AB  - OBJECTIVE: Our objective was to determine how readily disruption of the blood
      brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to
      implant microelectrodes in rat cortex. While the phenomenon of heat production
      during bone drilling is well known, practices to evade damage to the underlying
      brain tissue are inconsistently practiced and reported in the literature.
      APPROACH: We conducted a review of the intracortical microelectrode literature to
      summarize typical approaches to mitigate drill heating during rodent
      craniotomies. Post mortem skull-surface and transient brain-surface temperatures
      were experimentally recorded using an infrared camera and thermocouple,
      respectively. A number of drilling conditions were tested, including varying
      drill speed and continuous versus intermittent contact. In vivo BBB permeability
      was assayed 1 h after the craniotomy procedure using Evans blue dye. MAIN
      RESULTS: Of the reviewed papers that mentioned methods to mitigate thermal damage
      during craniotomy, saline irrigation was the most frequently cited (in six of
      seven papers). In post mortem tissues, we observed increases in skull-surface
      temperature ranging from  +3  degrees C to  +21  degrees C, dependent on drill
      speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000
      r.p.m.) were the most effective methods we studied to mitigate heating effects
      from drilling, while inconclusive results were obtained with saline irrigation.
      SIGNIFICANCE: Neuroinflammation, initiated by damage to the BBB and perpetuated
      by the foreign body response, is thought to play a key role in premature failure
      of intracortical recording microelectrodes. This study demonstrates the extreme
      sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to
      the BBB, the authors recommend that craniotomies be drilled with slow speeds
      and/or with intermittent drilling with complete removal of the drill from the
      skull during 'off' periods. While saline alone was ineffective at preventing
      overheating, its use is still recommended to remove bone dust from the surgical
      site and to augment other cooling methods.

PMID- 29205170
TI  - 45 degrees  sign switching of effective exchange bias due to competing
      anisotropies in fully epitaxial Co3FeN/MnN bilayers.
AB  - We report an unusual angular-dependent exchange bias effect in
      ferromagnet/antiferromagnet bilayers, where both ferromagnet and antiferromagnet
      are epitaxially grown. Numerical model calculations predict an approximately 45
      degrees  period for the sign switching of the exchange-bias field, depending on
      the ratio between magnetocrystalline anisotropy and exchange-coupling constant.
      The switching of the sign is indicative of a competition between a fourfold
      magnetocrystalline anisotropy of the ferromagnet and a unidirectional anisotropy
      field of the exchange coupling. This predicted unusual angular-dependent exchange
      bias and its magnetization switching process are confirmed by measurements on
      fully epitaxial Co3FeN/MnN bilayers by longitudinal and transverse magneto-optic
      Kerr effect magnetometry. These results provide a deeper understanding of the
      exchange coupling phenomena in fully epitaxial bilayers with tailored materials
      and open up a complex switching energy landscape engineering by anisotropies.

PMID- 29205171
TI  - Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe
      magnetic manipulation of ependymal cells in live rodents.
AB  - Tagging recognition group(s) on superparamagnetic iron oxide is known to aid
      localisation (imaging), stimulation and separation of biological entities using
      magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS)
      techniques. Despite the wide applicability of iron oxide nanoparticles in T 2
      weighted MRI and MAS, the quality of the images and safe manipulation of the
      exceptionally delicate neural cells in a live brain are currently the key
      challenges. Here, we demonstrate the engineered manganese oxide clusters-iron
      oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem
      cells (NSCs) imaging and magnetic manipulation in live rodents. As a result,
      using this engineered nanoparticle and associated technologies, identification,
      stimulation and transportation of labelled potentially multipotent NSCs from a
      specific location of a live brain to another by magnetic means for self-healing
      therapy can therefore be made possible.

PMID- 29205172
TI  - A data-driven approach for addressing the lack of flow waveform data in studies
      of cerebral arterial flow in older adults.
AB  - OBJECTIVE: Blood flow waveforms-essential data for hemodynamic modeling-are often
      in practice unavailable to researchers. The objectives of this work were to
      assess the variability among the waveforms for a clinically relevant older
      population, and develop data-based methods for addressing the missing waveform
      data for hemodynamic studies. APPROACH: We analyzed 272 flow waveforms from the
      internal carotid arteries of older patients (73  +/-  13 yr) with moderate
      cardiovascular disease, and used these data to develop methods to guide new
      approaches for hemodynamic studies. MAIN RESULTS: Profound variations in waveform
      parameters were found within the aged population that were not seen in published
      data for young subjects. Common features in the aged population relative to the
      young included a larger systole-to-diastole flow rate ratio, increased flow
      during late systole, and absence of a dicrotic notch. Eight waveforms were
      identified that collectively represent the range of waveforms in the older
      population. A relationship between waveform shape and flow rate was obtained
      that, in conjunction with equations relating flow rate to diameter, can be used
      to provide individualized waveforms for patient-specific geometries. The
      dependence of flow rate on diameter was statistically different between male and
      female patients. SIGNIFICANCE: It was shown that a single archetypal waveform
      cannot well-represent the diverse waveforms found within an aged population,
      although this approach is frequently used in studies of flow in the cerebral
      vasculature. Motivated by these results, we provided a set of eight waveforms
      that can be used to assess the hemodynamic uncertainty associated with the lack
      of patient-specific waveform data. We also provided a methodology for generating
      individualized waveforms when patient gender, age, and cardiovascular disease
      state are known. These data-driven approaches can be used to devise more relevant
      in vitro or in silico intra-cranial hemodynamic studies for older patients.

PMID- 29205173
TI  - Roadmap on semiconductor-cell biointerfaces.
AB  - This roadmap outlines the role semiconductor-based materials play in
      understanding the complex biophysical dynamics at multiple length scales, as well
      as the design and implementation of next-generation electronic, optoelectronic,
      and mechanical devices for biointerfaces. The roadmap emphasizes the advantages
      of semiconductor building blocks in interfacing, monitoring, and manipulating the
      activity of biological components, and discusses the possibility of using active
      semiconductor-cell interfaces for discovering new signaling processes in the
      biological world.

PMID- 29205174
TI  - Numerical implementation of magneto-acousto-electric tomography (MAET) using a
      linear phased array transducer.
AB  - In this study, the performance and implementation of magneto-acousto-electric
      tomography (MAET) is investigated using a linear phased array (LPA) transducer.
      The goal of MAET is to image the conductivity distribution in biological bodies.
      It uses the interaction between ultrasound and a static magnetic field to
      generate velocity current density distribution inside the body. The resultant
      voltage due to velocity current density is sensed by surface electrodes attached
      on the body. In this study, the theory of MAET is reviewed. A 16-element LPA
      transducer is used to provide beam directivity and steerability of acoustic
      waves. Different two-dimensional (2D) numerical models of breast and tumour are
      formed to analyze the multiphysics problem coupled with acoustics and
      electromagnetic fields. In these models, velocity current density distributions
      are obtained for pulse type ultrasound excitations. The static magnetic field is
      assumed as 1 Tesla. To sense the resultant voltage caused by the velocity current
      density, it is assumed that two electrodes are attached on the surface of the
      body. The performance of MAET is shown through sensitivity matrix analysis. The
      sensitivity matrix is obtained for two transducer positions with 13 steering
      angles between -30 degrees  to 30 degrees  with 5 degrees  angular intervals. For
      the reconstruction of the images, truncated singular value decomposition (SVD)
      method is used with different signal-to-noise ratio (SNR) values (20 dB, 40 dB,
      60 dB and 80 dB). The resultant images show that the perturbation (5 mm * 5 mm)
      placed 35 mm depth can be detected even if the SNR is 20 dB.

PMID- 29205175
TI  - Anomalous water dynamics at surfaces and interfaces: synergistic effects of
      confinement and surface interactions.
AB  - In nature, water is often found in contact with surfaces that are extended on the
      scale of molecule size but small on a macroscopic scale. Examples include lipid
      bilayers and reverse micelles as well as biomolecules like proteins, DNA and
      zeolites, to name a few. While the presence of surfaces and interfaces interrupts
      the continuous hydrogen bond network of liquid water, confinement on a mesoscopic
      scale introduces new features. Even when extended on a molecular scale, natural
      and biological surfaces often have features (like charge, hydrophobicity) that
      vary on the scale of the molecular diameter of water. As a result, many new and
      exotic features, which are not seen in the bulk, appear in the dynamics of water
      close to the surface. These different behaviors bear the signature of both water
      surface interactions and of confinement. In other words, the altered properties
      are the result of the synergistic effects of surface-water interactions and
      confinement. Ultrafast spectroscopy, theoretical modeling and computer
      simulations together form powerful synergistic approaches towards an
      understanding of the properties of confined water in such systems as
      nanocavities, reverse micelles (RMs), water inside and outside biomolecules like
      proteins and DNA, and also between two hydrophobic walls. We shall review the
      experimental results and place them in the context of theory and simulations. For
      water confined within RMs, we discuss the possible interference effects
      propagating from opposite surfaces. Similar interference is found to give rise to
      an effective attractive force between two hydrophobic surfaces immersed and kept
      fixed at a separation of d, with the force showing an exponential dependence on
      this distance. For protein and DNA hydration, we shall examine a multitude of
      timescales that arise from frustration effects due to the inherent heterogeneity
      of these surfaces. We pay particular attention to the role of orientational
      correlations and modification of the same due to interaction with the surfaces.

PMID- 29205176
TI  - Electrochemical characterization of high frequency stimulation electrodes: role
      of electrode material and stimulation parameters on electrode polarization.
AB  - OBJECTIVE: With recent interest in kilohertz frequency electrical stimulation for
      nerve conduction block, understanding the electrochemistry and role of electrode
      material is important for assessing the safety of these stimulus protocols. Here
      we describe an approach to determining electrode polarization in response to
      continuous kilohertz frequency sinusoidal current waveforms. We have also
      investigated platinum, iridium oxide, and titanium nitride as coatings for high
      frequency electrodes. The current density distribution at 50 kHz at the electrode
      electrolyte interface was also modeled to demonstrate the importance of the
      primary current distribution in supporting charge injection at high frequencies.
      APPROACH: We determined electrode polarization in response to sinusoidal currents
      with frequencies in the 1-50 kHz range and current amplitudes from 100 to 500 uA
      and 1-5 mA, depending on the electrode area. The current density distribution at
      the interface was modeled using the finite element method (FEM). MAIN RESULTS: At
      low frequencies, 1-5 kHz, polarization on the platinum electrode was significant,
      exceeding the water oxidation potential for high amplitude (5 mA) waveforms. At
      frequencies of 20 kHz or higher, the polarization was less than 300 mV from the
      electrode open circuit potential. The choice of electrode material did not play a
      significant role in electrode polarization at frequencies higher than 10 kHz. The
      current density distribution modeled at 50 kHz is non-uniform and this non
      uniformity persists throughout charge delivery. SIGNIFICANCE: At high frequencies
      (>10 kHz) electrode double-layer charging is the principal mechanism of charge
      injection and selection of the electrode material has little effect on
      polarization, with platinum, iridium oxide, and titanium nitride exhibiting
      similar behavior. High frequency stimulation is dominated by a highly nonuniform
      primary current distribution.

PMID- 29205177
TI  - Evaluation of latent variances in Monte Carlo dose calculations with Varian
      TrueBeam photon phase-spaces used as a particle source.
AB  - The purpose of this study was to evaluate the latent variance (LV) of Varian
      TrueBeam photon phase-space files (PSF) for open 10  *  10 cm2 and small
      stereotactic fields and estimate the number of phase spaces required to be summed
      up in order to maintain sub-percent LV in Monte Carlo (MC) dose calculations.
      BEAMnrc/DOSXYZnrc software was used to transport particles from Varian phase
      space files (PSFA) through the secondary collimators. Transported particles were
      scored into another phase-space located under the jaws (PSFB), or transported
      further through the cone collimators and scored straight below, forming PSFC.
      Phase-space files (PSFB) were scored for 6 MV-FFF, 6 MV, 10 MV-FFF, 10 MV and 15
      MV beams with 10  *  10 cm2 field size, and PSFC were scored for 6 MV beam under
      circular cones of 0.13, 0.25, 0.35, and 1 cm diameter. Both PSFB and PSFC were
      transported into a water phantom with particle recycling number ranging from 10
      to 1000. For 10  *  10 cm2 fields 0.5  *  0.5  *  0.5 cm3 voxels were used to
      score the dose, whereas the dose was scored in 0.1  *  0.1  *  0.5 cm3 voxels for
      beams collimated with small cones. In addition, for small 0.25 cm diameter cone
      collimated 6 MV beam, phantom voxel size varied as 0.02  *  0.02  *  0.5 cm3,
      0.05  *  0.05  *  0.5 cm3 and 0.1  *  0.1  *  0.5 cm3. Dose variances were scored
      in all cases and LV evaluated as per Sempau et al. For the 10  *  10 cm2 fields
      calculated LVs were greatest at the phantom surface and decreased with depth
      until they reached a plateau at 5 cm depth. LVs were found to be 0.54%, 0.96%,
      0.35%, 0.69% and 0.57% for the 6 MV-FFF, 6 MV, 10 MV-FFF, 10 MV and 15 MV
      energies, respectively at the depth of 10 cm. For the 6 MV phase-space collimated
      with cones of 0.13, 0.25, 0.35, 1.0 cm diameter, the LVs calculated at 1.5 cm
      depth were 75.6%, 25.4%, 17.6% and 8.0% respectively. Calculated LV for the 0.25
      cm cone-collimated 6 MV beam were 61.2%, 40.7%, 22.5% in 0.02  *  0.02  *  0.5
      cm3, 0.05  *  0.05  *  0.5 cm3 and 0.1  *  0.1  *  0.5 cm3 voxels respectively.
      In order to achieve sub-percent LV in open 10  *  10 cm2 field MC simulations a
      single PSF can be used, whereas for small SRS fields (0.13-1.0 cm) more PSFs (66
      8 PSFs) would have to be summed.

PMID- 29205178
TI  - Association of subcutaneous testosterone pellet therapy with developing secondary
      polycythemia.
AB  - A variety of methods for testosterone replacement therapy (TRT) exist, and the
      major potential risks of TRT have been well established. The risk of developing
      polycythemia secondary to exogenous testosterone (T) has been reported to range
      from 0.4% to 40%. Implantable T pellets have been used since 1972, and secondary
      polycythemia has been reported to be as low as 0.4% with this administration
      modality. However, our experience has suggested a higher rate. We conducted an
      institutional review board-approved, single-institution, retrospective chart
      review (2009-2013) to determine the rate of secondary polycythemia in 228 men
      treated with subcutaneously implanted testosterone pellets. Kaplan-Meyer failure
      curves were used to estimate time until the development of polycythemia
      (hematocrit >50%). The mean number of pellets administered was 12 (range: 6-16).
      The mean follow-up was 566 days. The median time to development of polycythemia
      whereby 50% of patients developed polycythemia was 50 months. The estimated rate
      of polycythemia at 6 months was 10.4%, 12 months was 17.3%, and 24 months was
      30.2%. We concluded that the incidence of secondary polycythemia while on T
      pellet therapy may be higher than previously established.

PMID- 29205179
TI  - Commentary on "Nondegloving technique for Peyronie's disease with penile
      prosthesis implantation and double dorsal-ventral patch graft".

PMID- 29205180
TI  - Androgen receptor deficiency in monocytes/macrophages does not alter adiposity or
      glucose homeostasis in male mice.
AB  - Androgen deprivation in men leads to increased adiposity, but the mechanisms
      underlying androgen regulation of fat mass have not been fully defined. Androgen
      receptor (AR) is expressed in monocytes/macrophages, which are resident in key
      metabolic tissues and influence energy metabolism in surrounding cells. Male mice
      bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were
      generated to determine whether selective loss of androgen signaling in these
      cells would lead to altered body composition. Wild-type (WT) and M-ARKO mice (12
      22 weeks of age, n = 12 per group) were maintained on a regular chow diet for 8
      weeks and then switched to a high-fat diet for 8 additional weeks. At baseline
      and on both the regular chow and high-fat diets, no differences in lean mass or
      fat mass were observed between groups. Consistent with the absence of
      differential body weight or adiposity, no differences in food intake (3.0 +/- 0.5
      g per day for WT mice vs 2.8 +/- 0.4 g per day for M-ARKO mice) or total energy
      expenditure (0.6 +/- 0.1 Kcal h-1 for WT mice vs 0.5 +/- 0.1 Kcal h-1 for M-ARKO
      mice) were evident between groups during high-fat feeding. Liver weight was
      greater in M-ARKO than that in WT mice (1.5 +/- 0.1 g vs 1.3 +/- 0.0 g,
      respectively, P = 0.02). Finally, M-ARKO mice did not exhibit impairments in
      glucose tolerance or insulin sensitivity relative to WT mice at any study time
      point. In aggregate, these findings suggest that AR signaling specifically in
      monocytes/macrophages does not contribute to the regulation of systemic energy
      balance, adiposity, or insulin sensitivity in male mice.

PMID- 29205181
TI  - Feasibility of the conversion of percutaneous cholecystostomy to internal
      transmural endoscopic ultrasound-guided gallbladder drainage.

PMID- 29205182
TI  - Association between gastroesophageal reflux disease and nonalcoholic fatty liver
      disease: A meta-analysis.
AB  - BACKGROUND/AIM: The relationship between gastroesophageal reflux disease (GERD)
      and nonalcoholic fatty liver disease (NAFLD) has been demonstrated in recent
      epidemiologic studies although the results were inconsistent. This meta-analysis
      was conducted to summarize all available data and to estimate the risk of NAFLD
      among patients with GERD. MATERIALS AND METHODS: Comprehensive literature review
      was conducted using MEDLINE and EMBASE database from inception through November
      2016, to identify studies that compared the risk of NAFLD among patients with
      GERD versus those without GERD. Effect estimates from each study were extracted
      and combined using the random-effect, generic inverse variance method of
      DerSimonian and Laird. RESULTS: Eight studies (four cross-sectional studies and
      four case-control studies) with 31,322 participants met the eligibility criteria
      and were included in the meta-analysis. The risk of NAFLD among patients with
      GERD was significantly higher than those without GERD with the pooled odds ratio
      of 2.07 (95% confidence interval, 1.54-2.79). The statistical heterogeneity was
      high with an I2 of 87%. CONCLUSIONS: A significantly increased risk of NAFLD
      among patients with GERD was observed in this meta-analysis.

PMID- 29205183
TI  - Feasibility of conversion of percutaneous cholecystostomy to internal transmural
      endoscopic ultrasound-guided gallbladder drainage.
AB  - BACKGROUND/AIM: Percutaneous cholecystostomy [percutaneous transhepatic
      gallbladder drainage (PTGBD)] is the treatment of choice in surgically unfit
      patients with acute cholecystitis. However, PTGBD tube removal after symptoms
      resolution results in 41-46% recurrence. This study aims to demonstrate the
      feasibility of the conversion of PTGBD to transmural endoscopic ultrasound-guided
      gallbladder drainage (EUS-GBD) using plastic stents in patients unfit for
      cholecystectomy. PATIENTS AND METHODS: Patients who underwent internal transmural
      EUS-GBD as a conversion from PTGBD were reviewed. EUS-GBD was performed after the
      improvement of cholecystitis due to recurrent cholecystitis and PTGBD
      intolerance. One or two 7-Fr double pigtail plastic stent insertion with or
      without temporary endoscopic naso-gallbladder drainage (ENGBD) insertion was
      performed. RESULTS: Six patients (age 61-88), with three cases of acute
      cholecystitis after metallic biliary stenting and three cases of calculus
      cholecystitis, who underwent PTGBD were included. EUS-GBD was performed 10-63
      days after PTGBD, using one plastic stent in five cases, two stents in one case,
      with temporary ENGBD in two cases. The technical success and clinical success
      were achieved and the PTGBD tubes were subsequently removed in all patients. All
      ENGBD tubes were removed within 5 days after insertion. Bile leak with
      peritonitis was demonstrated in one case, which was treated conservatively. No
      recurrent cholecystitis was seen during 3-26 months of follow-up. CONCLUSION: The
      conversion of percutaneous cholecystostomy to internal transmural EUS-GBD with
      plastic stents is feasible for patients unfit for cholecystectomy. However, more
      studies are still needed to confirm the results.

PMID- 29205184
TI  - Adipose-derived mesenchymal stem cells suppress of acute rejection in small bowel
      transplantation.
AB  - BACKGROUND/AIMS: Adipose-derived mesenchymal stem cells (ADSCs) possess
      immunosuppressive activity and hold promise in autologous cell-based therapies.
      The aim of this study was to determine whether autologous ADSCs can improve
      outcomes in the rat small bowel transplantation (SBT) model. MATERIALS AND
      METHODS: Allogeneic SBT followed by implantation of autologous ADSCs through the
      penile vein was conducted in Brown-Norway (BN) donor rats with Lewis (LEW)
      recipient rats infused with phosphate buffered solution as the control. Allograft
      and recipient peripheral blood were obtained. We assessed histopathology,
      apoptosis, cytokines, and regulatory T cells (Tregs). One-way analysis of
      variance was applied to assess the significance of the data. RESULTS: It was
      found that ADSCs significantly reduced acute rejection and improved the
      allograft's survival rate. In addition, there were significantly fewer apoptotic
      cells in allograft mucosae in the ADSC group in comparison with the control
      group. Furthermore, levels of interleukin (IL)-10 and transforming growth factor
      beta1 were significantly elevated, whereas those of IL-2 and IL-17 levels were
      significantly reduced in the ADSC group when compared to the control group.
      Moreover, flow cytometry analysis revealed that there were significantly more
      peripheral Tregs after the infusion of ADSCs. CONCLUSIONS: These results
      demonstrate that implanted autologous ADSCs improve allogeneic small bowel
      allograft outcomes by attenuating the acute rejection and reducing inflammatory
      responses.

PMID- 29205185
TI  - Knowledge, attitude, and practices of primary health care physicians toward
      colorectal cancer screening.
AB  - BACKGROUND/AIM: Early diagnosis of chronic illnesses and cancers mainly occurs at
      primary health care centers (PHCs) by primary health care physicians (PHPs). The
      incidence of colorectal cancer (CRC) in the Kingdom of Saudi Arabia (KSA) is
      rising and this has been attributed to many factors. The increasing incidence of
      CRC is compounded by nonadherence to screening recommendations. Therefore,
      evaluating PHPs knowledge, attitudes, and practices of screening for CRC is
      clinically important. We aimed to evaluate the knowledge, attitudes, and
      practices of PHPs regarding CRC screening and to identify the factors associated
      with nonadherence of PHPs to screening recommendations. MATERIALS AND METHODS:
      PHPs working at three tertiary care centers and PHCs across the city of Jeddah
      were randomly recruited. Participants were surveyed using a comprehensive
      questionnaire that recorded data on demographics, qualifications, and knowledge
      of various modalities and guidelines related to CRC screening. Perspectives about
      effectiveness of, or adherence to, factors that influence physicians'
      perspectives or recommendations for CRC screening were also assessed. Logistic
      regression analysis was used to identify physician characteristics associated
      with PHPs perspectives and nonadherence to CRC screening. RESULTS: A total of 127
      PHPs were recruited. The average age of participants was 34 (+/-8.4) years, 86.6%
      were native Saudi's and 56.7% were females. The majority of surveys (66.9%) were
      completed at 24 PHCs and the remaining at hospital-based family medicine clinics.
      Most of the PHPs (55%) had a bachelor's degree and 31.5% were board-certified or
      carried a PhD in family medicine; 95% of participants believed that CRC screening
      in general was effective, but as much as 55% reported that they did not practice
      screening. The male physicians [odds ratio (OR) = 0.44, 95% confidence interval
      (CI) = 0.19-0.99, P = 0.048)] and PHPs with only a bachelor degree or less (OR =
      0.72, 95% CI = 0.55-0.93, P = 0.011) were less likely to recommend screening for
      CRC. CONCLUSIONS: A considerable proportion of PHPs do not adhere to CRC
      screening recommendations despite a wide belief that screening is effective. Male
      PHPs with lower qualifications appear to be less likely to recommend screening.

PMID- 29205186
TI  - A cross-sectional survey of multi-generation inflammatory bowel disease
      consanguinity and its relationship with disease onset.
AB  - : Background?Aim: Consanguinity influences the phenotypic variations of some
      hereditary and immune-mediated disorders, including inflammatory bowel disease.
      This study estimated the prevalence of consanguinity among the ancestors of
      patients with inflammatory bowel disease and examined the effect of various
      consanguinity levels on inflammatory bowel disease onset. PATIENTS AND METHODS:
      Patients with inflammatory bowel disease who were seen at two gastroenterology
      outpatient clinics were consecutively recruited and surveyed for demographics,
      disease onset, and presence of ancestral consanguinity within three generations.
      The prevalence of different consanguinity levels was calculated. The association
      between age at inflammatory bowel disease onset and consanguinity was examined.
      RESULTS: Two hundred seventeen patients were recruited. The mean age, mean age at
      diagnosis, and mean illness duration were 32.9 +/- 13.4, 18.6 +/- 11.5, and 8.6
      +/- 7.7 years, respectively. Of the cohort, 53.5% were women, and 74.2% were
      native Saudis. Cigarette smoking was reported in 17.1%; 51% had Crohn's disease,
      while the remaining patients had ulcerative colitis. A family history of
      inflammatory bowel disease was reported in 29.5% of patients; consanguinity
      within three generations was reported in 57.6%. Consanguinity in more than one
      generation was reported in 38.7%; 17.5% had consanguinity in three consecutive
      generations. There was no association between inflammatory bowel disease onset
      and multi-generation consanguinity, but there was an association with disease
      subtype in favor of ulcerative colitis (b coefficient = 7.1 [95% confidence
      interval = 4.1, 10]). CONCLUSIONS: Consanguinity is extremely common among Saudi
      patients with inflammatory bowel disease but does not seem to influence age at
      disease onset. Genetic studies are needed to further clarify the effect of
      consanguinity on disease behavior.

PMID- 29205187
TI  - A CT-guided fat transversing coaxial biopsy technique for pancreatic lesion
      biopsy that avoids major organs and vessels.
AB  - BACKGROUND/AIMS: The purpose of this study is to report our results using a
      computed tomography (CT)-guided fat transversing coaxial biopsy technique for
      pancreatic lesion biopsy that avoids major organs and vessels. We retrospectively
      reviewed the records of patients referred to our department for pancreatic mass
      biopsy. PATIENTS AND METHODS: The records of patients (from June 2008 to August
      2014) in whom biopsy was performed under CT guidance with a coaxial needle using
      a fat transversing technique were reviewed. Patient demographic data and biopsy
      outcomes were collected. We aimed to compare differences between lesion size and
      biopsy outcome, the independent two-samples t-test was used. RESULTS: A total of
      122 patients who underwent 17-G coaxial needle biopsy were included. The mean
      pancreatic lesion size was 3.2 cm, and in 30 patients it was more than 4 cm. The
      majority of lesions were located in the head of the pancreas (44.3%). No
      transorgan biopsies were performed. In most patients, the biopsy was performed
      via a fat traversing detour route (93.4%), and a successful diagnosis was made
      based on the biopsy outcome in 96.7% patients. Complications occurred in five
      patients (4.1%); three of the patients developed a fever, and two developed
      pancreatitis. All patients recovered with symptomatic treatment. CONCLUSION: CT
      guided coaxial core biopsy of pancreatic lesions using a fat detour route appears
      to be a safe and effective method for obtaining pancreatic lesion biopsies with a
      high success rate and low complication rate.

PMID- 29205188
TI  - Validity and clinical impact of glucose transporter 1 expression in colorectal
      cancer.
AB  - BACKGROUND/AIM: There is no doubt that colorectal cancer (CRC) poses a major
      threat to public health worldwide, and despite improvement in managements,
      prognosis still remains an irritating question with no definite answer. Being a
      fundamental player in cancer metabolism, glucose transporter 1 (GLUT1) could be
      utilized as a prognostic biomarker that could fuel development of new treatment
      strategies. The aim of this study was to assess the validity of GLUT1 expression
      as a prognostic biomarker and to elucidate to what extent it is immersed in poor
      clinical outcome among CRC patients. PATIENTS AND METHODS: GLUT1 expression in
      peripheral blood specimens was analyzed by quantitative real-time polymerase
      chain reaction in 47 CRC patients and 20 healthy controls. RESULTS: There was
      significantly elevated GLUT1 expression in peripheral blood of CRC patients than
      in controls (P < 0.001). The cutoff value of 0.605 provided 98% sensitivity and
      100% specificity. There were significantly higher values of GLUT1 expression in
      patients under 50 years (P = 0.003), performance status 2 (P = 0.009), stage IV
      (P < 0.001), and presence of metastasis (P < 0.001). GLUT1 expression showed
      nonsignificant association with overall survival (P = 0.068), while tumor stage
      (P = 0.01) and metastasis (P = 0.009) were significantly associated with lower
      overall survival. CONCLUSION: GLUT1 is sensitive and specific marker for CRC. It
      is overexpressed in young age patients, poor performance status, and stage IV
      patients. Although this was not statistically significant, GLUT 1 showed higher
      expression level in patients with lesser survival.

PMID- 29205189
TI  - Staphylococcus aureus biofilm removal by targeting biofilm-associated
      extracellular proteins.
AB  - BACKGROUND & OBJECTIVES: Among cell surface proteins, biofilm-associated protein
      (Bap) promotes biofilm development in Staphylococcus aureus strains. The aim of
      this study was to investigate proteinase-mediated biofilm dispersion in different
      isolates of S. aureus. METHODS: Biofilm assay was done in 96-well microtitre
      plate to evaluate the effect of proteinase K on biofilms of bovine mastitis S.
      Aureus isolates. Extracellular polymeric substances were extracted and evaluated
      for their composition (protein, polysaccharides and extracellular DNA), before
      and after the proteinase K treatment. RESULTS: Biofilm assay showed that 2 MUg/ml
      proteinase K significantly inhibited biofilm development in bap-positive S.
      aureus V329 as well as other S. aureus isolates (SA7, SA10, SA33, SA352), but not
      in bap-mutant M556 and SA392 (a weak biofilm-producing strain). Proteinase K
      treatment on S. aureus planktonic cells showed that there was no inhibition of
      planktonic growth up to 32 MUg/ml of proteinase K. Proteinase K treatment on 24 h
      old preformed biofilms showed an enhanced dispersion of bap-positive V329 and
      SA7, SA10, SA33 and SA352 biofilms; however, proteinase K did not affect the bap
      mutant S. aureus M556 and SA392 biofilms. Biofilm compositions study before and
      after proteinase K treatment indicated that Bap might also be involved in eDNA
      retention in the biofilm matrix that aids in biofilm stability. When proteinase K
      was used in combination with antibiotics, a synergistic effect in antibiotic
      efficacy was observed against all biofilm-forming S. aureus isolates.
      INTERPRETATION & CONCLUSIONS: Proteinase K inhibited biofilms growth in S. aureus
      bovine mastitis isolates but did not affect their planktonic growth. An enhanced
      dispersion of preformed S. aureus biofilms was observed on proteinase K
      treatment. Proteinase K treatment with antibiotics showed a synergistic effect
      against S. aureus biofilms. The study suggests that dispersing S. aureus by
      protease can be of use while devising strategies againstS. aureus biofilms.

PMID- 29205190
TI  - Characterization of antimicrobial resistance markers & their stability in
      Salmonella enterica serovar Typhi.
AB  - BACKGROUND & OBJECTIVES: Typhoid fever is a major cause of morbidity and
      mortality in the developing countries including India. Resistance to multiple
      antimicrobial agents is an emerging global problem that has serious impact on the
      treatment of disease. There are many factors associated with the emergence of
      resistance. Most important of them is the acquisition and further transmission
      and spread of resistance markers among various bacterial species. Therefore, we
      conducted this study to characterize the resistance plasmids in terms of their
      transferability and stability among Salmonella enterica serovar Typhi. METHODS:
      Six multidrug-resistant S. Typhi isolates were evaluated for the stability and
      transfer of resistance markers. The resistance plasmids were also checked for the
      presence of RepHI1A replicon. RESULTS: All resistance markers were found to be
      transferred to the recipient through conjugation and transformation, except for
      nalidixic acid. None of the resistance plasmid was found to harbour RepHI1A
      replicon and therefore, did not belong to incompatibility group IncHI1.
      Resistance markers were found to be highly stable in all the isolates during
      serial passages and storage as stab cultures at different temperatures for
      different time periods. INTERPRETATION & CONCLUSIONS: Resistance markers for
      chloramphenicol, ampicillin, streptomycin and trimethoprim were transferred
      through conjugation as well as transformation whereas that for nalidixic acid was
      not transferred in any of the isolates. Markers for chloramphenicol and
      streptomycin resistance were found to be most stable during various storage
      conditions. Presence of small-sized non-IncHI1 resistance plasmids is a matter of
      concern due to their capability to exist inside the host, thereby increasing the
      possibility of their transmission and spread among S. Typhi and other bacterial
      species.

PMID- 29205191
TI  - Investigation into a community outbreak of Salmonella Typhi in Bengaluru, India.
AB  - BACKGROUND & OBJECTIVES: Outbreaks of infection due to Salmonella enterica
      servovar Typhi (S. Typhi) are a great threat to public health. A rapid molecular
      typing method to characterize strains implicated in an outbreak is critical in
      implementing appropriate control measures. This study was done to demonstrate the
      power of a PCR-based method to provide rapid insights into the genetic
      relatedness amongst the Salmonella isolates implicated in a suspected typhoid
      fever outbreak. METHODS: Forty two S. Typhi isolates originating from three
      geographically distinct areas, with one area suspected to have a single-source
      outbreak were included in the study. The genetic fingerprint of all isolates was
      generated using enterobacterial repetitive intergenic consensus sequence based
      PCR (ERIC-PCR). The antimicrobial susceptibility profiles were also evaluated.
      RESULTS: ERIC-PCR was found to be rapid and reproducible with a discriminatory
      index of 0.766. The dendrogram constructed based on ERIC-PCR fingerprinting
      revealed the existence of 12 distinct genotypes. The location suspected to have
      an outbreak displayed two genotypes amongst the 24 isolates. The other two
      locations (18 isolates) displayed genetic heterogeneity. The clonality of the
      outbreak isolates from the time-matched control isolates was established. The
      observed antimicrobial susceptibility profiles did not have any discriminatory
      power to subtype the isolates compared to the genetic fingerprints.
      INTERPRETATION & CONCLUSIONS: Our study demonstrated the discriminatory power and
      value of ERIC-PCR in the typing of S. Typhi isolates and providing valuable
      epidemiological insights.

PMID- 29205192
TI  - Genetic diversity study of various beta-lactamase-producing multidrug-resistant
      Escherichia coli isolates from a tertiary care hospital using ERIC-PCR.
AB  - BACKGROUND & OBJECTIVES: The prevalence of multidrug-resistant (MDR) Escherichia
      coli isolates producing beta-lactamase enzyme is a growing problem across the
      globe. Strain typing is an epidemiologically important tool not only for
      detecting the cross transmission of nosocomial pathogens but also for determining
      the source of infection. The present study was conducted to understand the clonal
      relationship among various beta-lactamase-producing MDR E. coli isolates using
      enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction
      (PCR). METHODS: A total of 41 MDR E. coli isolates were randomly collected from
      various clinical samples and processed. Isolated organisms were tested for
      antibiotics resistance pattern. Phenotypic detection of metallo beta-lactamases
      (MBL) was carried out by the imipenem-ethylenediaminetetraacetic acid disc
      diffusion/double-disc synergy test. AmpC enzyme production was tested by a
      modified three-dimensional extract test. RESULTS: Almost all isolates were found
      sensitive to colistin. A high percentage of drug resistance was observed in these
      isolates against ceftazidime (100%), cefotaxime (100%), cefepime (100%),
      ofloxacin (97.56%), amoxicillin/clavulanic acid (97.56%) and norfloxacin
      (85.36%). Of the 41 isolates, ESBL producers were found to be predominant, i.e.,
      22 (53.65%), followed by AmpC (6, 14.63%) and MBL (5, 12.19%). INTERPRETATION &
      CONCLUSIONS: At 60 per cent similarity cut-off value, the dendrogram analysis
      showed that there were a total of 14 unique clusters of ERIC (CL-1 - CL-14)
      within the 41 E. coli isolates, which revealed the genetic diversity existing
      between them.

PMID- 29205193
TI  - Molecular characterization of locus of enterocyte effacement pathogenicity island
      in shigatoxic Escherichia coli isolated from human & cattle in West Bengal,
      India.
AB  - BACKGROUND & OBJECTIVES: Shigatoxic Escherichia coli (STEC) recovered from dairy
      animals of Kolkata, India, harboured the putative virulence genes; however, the
      animals did not exhibit clinical symptoms. Similarly, human isolates in this
      locality also showed variations in degree of symptoms. Hence, this study was
      designed to know the presence of recognized gene(s) in the locus of enterocyte
      effacement (LEE) pathogenicity island in these STEC isolates and functional
      status of the cardinal gene (eae) related to pathogenicity. METHODS: Genes were
      characterized using polymerase chain reaction (PCR) assays, and functional status
      of cardinal gene (eae) was evaluated by fluorescent actin staining (FAS) assay.
      Variation in eae gene was determined by intimin PCR. RESULTS: Cattle STEC
      isolates carried 22 genes in LEE pathogenicity island in different frequencies
      ranging from 5.63 to 47.88 per cent of the isolates. In human isolates, the genes
      namely ler, escRSTU, orf 2, esc C, esc V, orf 3 and tir that are associated with
      secretory function, were found to be absent and rest of the genes were present in
      lower frequency. Further, the cardinal gene (eae) responsible for initiation of
      pathogenesis was in a very low frequency in human (n=2; 10.5%) and cattle (n=11;
      15.5%) isolates. None of theseeae+ STEC isolates from human and cattle revealed
      positivity in FAS assay. INTERPRETATION & CONCLUSIONS: Majority of human STEC
      isolates lacked the cardinal virulence gene (eae), and genes for secretory
      function that are essential for facilitating pathogenesis. This may partially be
      attributed to low occurrence of STEC in human clinical diarrhoea in this area.
      Although a few isolates (11 of 71) from cattle had eae gene, they did not express
      phenotypically. This could be one of the reasons for not appearing of clinical
      symptoms in the hosts.

PMID- 29205194
TI  - Analysis of beta-lactamases, blaNDM-1phylogeny & plasmid replicons in multidrug
      resistant Klebsiella spp. from a tertiary care centre in south India.
AB  - BACKGROUND & OBJECTIVES: beta-lactamases play a predominant role in drug
      resistance amongst Enterobacteriaceae. Presence of genes on transferable plasmids
      encoding these enzymes favours their dissemination across species and genera
      within and outside geographical boundaries. This study was aimed to understand
      the presence of beta-lactamases and transferable plasmids in clinical isolates of
      Klebsiella spp. which can contribute to the spread of resistance determinants.
      METHODS: A total of 41 clinical isolates of Klebsiella spp., collected from a
      tertiary care centre in Kerala, India, were checked for antibiotic sensitivity
      and the presence of plasmids. The ability to produce extended-spectrum beta
      lactamases (ESBLs) and metallo-beta-lactamases (MBLs) was screened for and
      confirmed in 29 plasmid-harbouring isolates. blaNDM-1-specific primers were used
      for polymerase chain reaction amplification with plasmid DNA as template to
      determine episomal prevalence of this gene and its sequence-based phylogeny
      employing similar sequences from GenBank. Plasmid replicon typing was also
      carried out to determine the presence of transferable plasmids. RESULTS: Our
      results showed a high degree of multidrug-resistant (MDR) pathogens with ESBL
      production confirmed in 52 per cent, MBL in 31 per cent and co-production of both
      enzymes in seven per cent of the plasmid-bearing isolates. Plasmid DNA from 14
      per cent of the isolates produced blaNDM-1-specific amplicons which showed
      sequence homology with those from bacteria of different genera and geographical
      areas. The predominant replicon type was found to be that of conjugative plasmids
      belonging to the incompatibility group - IncFIIK. INTERPRETATION & CONCLUSIONS:
      This study provides insight into the predominance of various beta-lactamases and
      potent gene-disseminating agents in Klebsiella spp. and emphasizes the need for
      constant surveillance of these pathogens to determine appropriate treatment
      strategies.

PMID- 29205195
TI  - Coexistence of metallo-beta-lactamase-encoding genes in Pseudomonas aeruginosa.
AB  - BACKGROUND & OBJECTIVES: The emergence and rapid spread of carbapenem resistance
      mediated by metallo-beta-lactamase (MBL) in Pseudomonas aeruginosa is of major
      concern due to limited therapeutic options. This study was aimed at detecting the
      presence of MBL and its association with integrons in imipenem-resistant P.
      aeruginosa isolates and to determine their genetic relatedness. METHODS: A total
      of 213 P. aeruginosa isolates were collected from two tertiary care centres and
      tested against anti-pseudomonal antibiotics by antimicrobial susceptibility
      testing, followed by the detection of MBL production by combined disk method.
      Minimum inhibitory concentration (MIC) of meropenem was determined by E-test.
      Multiplex polymerase chain reaction (PCR) was performed for the detection of
      blaSPM, blaIMP, blaVIM, blaNDM, blaGIM and blaSIM. PCR was carried out to
      characterize the variable region of class 1 integron. Transcongujation assay was
      carried out for the confirmation of plasmid-mediated resistance. Enterobacterial
      repetitive intergenic consensus sequence (ERIC)-PCR was performed for determining
      the genetic relatedness among P. aeruginosa isolates. RESULTS: Of the 213 P.
      aeruginosa isolates, 22 (10%) were found to be carbapenem resistant and these
      were from pus 18 (82%), urine 2 (9%), sputum 1 (5%) and tracheal wash 1 (5%).
      Among 22 isolates, 18 (81.8%) were found to be MBL producers by phenotypic method
      and MIC range of meropenem was 8 to >32 MUg/ml. PCR amplification showed that 20
      (91%) isolates carried any one of the MBL genes tested: blaVIM and blaNDM in
      seven (32%) and six (27%) isolates, respectively; blaVIM and blaNDMin three
      (14%); blaIMP and blaNDM in two (9%); blaVIM and blaIMP in one (5%) isolate. The
      blaVIM, blaIMP and blaNDM were found to co-exist in one isolate. None of the
      isolates were positive for blaSPM, blaSIM and blaGIM. All 22 isolates carried
      class I integron. Of the 20 MBL-positive isolates, transconjugants were obtained
      for 15 isolates. ERIC-PCR analysis showed all isolates to be clonally
      independent. INTERPRETATION & CONCLUSIONS: Our results showed 10.3 per cent of
      carbapenem resistance among P. aeruginosa isolates, and the coexistence of MBL
      encoding genes among P. aeruginosa mediated by class I integron.

PMID- 29205196
TI  - Speciation, clinical profile & antibiotic resistance in Aeromonas species
      isolated from cholera-like illnesses in a tertiary care hospital in north India.
AB  - BACKGROUND & OBJECTIVES: Aeromonas species have been reported to cause various
      illnesses in humans such as wound infections, septicaemia, peritonitis and
      pneumonia. Their role in causation of cholera-like illness is also being
      increasingly recognized. This retrospective study was done to know the presence
      of Aeromonas as a cause of acute diarrhoea in a tertiary care hospital and to
      find the common species of Aeromonas causing diarrhoea and their antibiotic
      susceptibility patterns. METHODS: Fifty isolates of Aeromonas were obtained over
      a period of 15 yr from 2000 to 2014 from patients of suspected acute
      gastroenteritis resembling cholera. Biotyping was done for 35 of these isolates
      available in culture collection, based on a panel of 13 biochemical reactions.
      Antibiogram was put up for all of these isolates by disk diffusion methods and
      interpreted according to the Clinical and Laboratory Standards Institute
      guidelines. RESULTS: Of the 50 patients of Aeromonas-related acute
      gastroenteritis, 13 (26%) had typical features of cholera with rice water stools
      and severe dehydration. Eight patients (16%) had dysentery-like picture. One
      patient died of severe dehydration and septicaemia. The most common species were
      found to be Aeromonas caviae (34%) followed by Aeromonas veronii biovar veronii
      (29%), Aeromonas veronii biovar sobria (26%) and Aeromonas hydrophila (9%). All
      tested isolates were uniformly susceptible to cefepime, amikacin, azithromycin
      and meropenem; 14 per cent were susceptible to amoxicillin, 32 per cent to
      nalidixic acid, 60 per cent to co-trimoxazole, 54 per cent to ciprofloxacin, 60
      per cent to ofloxacin, 74 per cent to chloramphenicol, 76 per cent to
      ceftriaxone, 74 per cent to cefotaxime, 88 per cent to gentamicin and 86 per cent
      to furoxone. INTERPRETATION & CONCLUSIONS: Aeromonas is an important, often
      neglected pathogen capable of causing a variety of gastrointestinal tract
      symptoms such as acute diarrhoea and dysentery and may even mimic cholera. It is,
      therefore, pertinent to recognize this pathogen as an important agent in the
      causation of severe diarrhoea.

PMID- 29205197
TI  - Detection of Chlamydia trachomatis infections by polymerase chain reaction in
      asymptomatic pregnant women with special reference to the utility of the pooling
      of urine specimens.
AB  - BACKGROUND & OBJECTIVES: Genital Chlamydia trachomatis (CT) infections are one of
      the most prevalent sexually transmitted infections across the world. In pregnant
      women, if not detected and treated early, these may result in poor pregnancy
      outcomes and complications. The present study was aimed to screen CT infections
      from first void urine (FVU) samples of asymptomatic pregnant women using
      molecular methods. The secondary objective was to evaluate cost-effectiveness in
      pooling FVU samples for their diagnostic application. METHODS: FVU samples were
      collected from 1000 asymptomatic pregnant women over a period of three years.
      Pooling was done by including five specimens in one pool in the amount of 10 MUl
      and subjected to polymerase chain reaction (PCR) and further confirmed by direct
      fluorescent antibody assay (DFA). RESULTS: The age of study participants ranged
      from 18 to 43 yr with the median+/-standard deviation of 26+/-3.84 yr. Majority
      of positive participants were younger than 25 years. A total of 200 pools were
      prepared and 20 of these were PCR positive. When individual specimen in 20
      positive pools was tested, 20 PCR-positive specimens were identified from 19
      pools, of which 16 were positive by DFA. Thus, CT was detected in 1.6 per cent
      asymptomatic pregnant women in India and pooling strategy resulted in 70 per cent
      reduction in a number of tests performed. INTERPRETATION & CONCLUSIONS: Our study
      detected C. trachomatis infection in 1.6 per cent asymptomatic pregnant women,
      and pooling of FVU specimens for PCR testing was found to be a cost-saving
      strategy in comparison to testing individual samples. Further evaluation and
      studies on the bigger sample size are warranted to validate these results.

PMID- 29205198
TI  - Exploring quinolone resistance-determining region in Neisseria gonorrhoeae
      isolates from across India.
AB  - BACKGROUND & OBJECTIVES: Antimicrobial resistance in Neisseria gonorrhoeae, the
      causative agent of gonorrhoea, is a subject of worldwide attention. The present
      study was undertaken to examine the rates of ciprofloxacin resistance, to
      correlate mutations in gyrA and parC genes with the level of resistance and to
      look for a variation in mutation pattern, if any, in isolates from across the
      country. METHODS: A total of 113 isolates of N. gonorrhoeae collected from
      sexually transmitted infection patients in six centres during November 2010 to
      October 2013 were investigated. Minimum inhibitory concentration (MIC)
      determination was done by E-test and results interpreted as per Calibrated
      Dichotomous Sensitivity criteria. DNA sequence analysis of gyrA and parC genes
      was done. RESULTS: Of the 113 isolates, only three (2.6%) were susceptible
      whereas eight (7.07%) were less susceptible, 32 [28.3%, 95% confidence interval
      (CI): 20.4-37.6%] resistant (MIC 1-3 MUg/ml) and 70 (61.9%, 95% CI: 52.2-70.7%)
      exhibited high-level resistance (HLR) (MIC >=4 MUg/ml) to ciprofloxacin. A S91F
      substitution in gyrA gene was demonstrated in all ciprofloxacin non-susceptible
      isolates. All resistant and HLR isolates had a double mutation in gyrA gene.
      However, only 5.7 per cent of HLR isolates showed double mutations in parC gene.
      One isolate (MIC 32 MUg/ml) had a previously undescribed G85D substitution in the
      parC gene. INTERPRETATION & CONCLUSIONS: A S91F substitution in gyrA gene was
      seen in all non-susceptible isolates of N. gonorrhoeae. It may be used as a
      marker for ciprofloxacin resistance for molecular surveillance approaches to
      complement the culture-based methods.

PMID- 29205199
TI  - Seroprevalence of Japanese encephalitis virus & West Nile virus in Alappuzha
      district, Kerala.
AB  - BACKGROUND & OBJECTIVES: Several outbreaks of acute encephalitis syndrome (AES)
      have been reported in Alappuzha district, Kerala State, India, in the past. The
      aetiology of these outbreaks was either inconclusive or concluded as probable
      Japanese encephalitis virus (JEV) infection based on clinical presentation. The
      role of West Nile virus (WNV) in AES outbreaks was also determined. However, the
      extent of WNV infection has not been studied in this region previously. A
      population-based cross-sectional serosurvey study was undertaken to determine the
      seroprevalence of JEV and WNV in Alappuzha district. METHODS: A total of 30
      clusters were identified from 12 blocks and five municipalities as per the
      probability proportional to size sampling method. A total of 1125 samples were
      collected from all age groups. A microneutralization assay was performed to
      estimate the prevalence of JEV and WNV neutralizing antibodies in the sample
      population. RESULTS: Of 1125 serum samples tested, 235 [21.5%, 95% confidence
      interval (CI): 15.2-27.8%] and 179 (15.9%, 95% CI: 9.6-22.3%) were positive for
      neutralizing antibodies against WNV and JEV, respectively. In addition, 411
      (34.5%, 95% CI: 26.7-42.2%) were positive for cross-reactive antibodies against
      flaviviruses. INTERPRETATION & CONCLUSIONS: The study showed the seroprevalence
      of WNV and JEV antibodies in the surveyed area and the WNV seroprevalence was
      greater than JEV. It is necessary to create awareness in public and adopt
      suitable policy to control these diseases.

PMID- 29205201
TI  - Surgery in 2017: Moving towards successful penile transplantation programmes.

PMID- 29205200
TI  - Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint
      inhibition.
AB  - Immunotherapy has been used in localized urothelial carcinoma for decades,
      especially in the treatment of superficial disease, in which instillation of BCG
      is a commonly used treatment option. Clinical investigations based on new
      insights into the immunogenic potential of metastatic urothelial carcinoma have
      led to the accelerated FDA approval of the immune checkpoint inhibitors
      atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary
      findings suggest additional benefits of combinations of immunotherapeutic agents
      as a future treatment approach in metastatic urothelial carcinoma. Treatment
      experience with immunotherapy suggests that these drugs are associated with a
      unique spectrum of immune-related adverse events and specific immune-related
      patterns of response, including cases of pseudoprogression, which could impede
      the optimal use of immune checkpoint inhibitors in the clinic. Appropriate
      management of immune-related adverse events and a greater awareness of immune
      mediated response patterns will help to inform treatment decisions and improve
      patient outcomes; predictive biomarkers of response might facilitate selection of
      patients who are most likely to respond to and benefit from these exciting new
      treatments.

PMID- 29205202
TI  - Prostate cancer: Stuck in the middle: interstitial genes in TMPRSS2-ERG fusion.

PMID- 29205203
TI  - Bladder cancer: Genomics of noninvasive disease.

PMID- 29205204
TI  - MTHFR, TS and XRCC1 genetic variants may affect survival in patients with
      myelodysplastic syndromes treated with supportive care or azacitidine.
AB  - We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA
      synthesis and DNA repair enzymes on the clinical outcome of 108 patients with
      myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or
      azacitidine. A statistically significant association between
      methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'
      untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and
      short survival was found in patients receiving BSC by multivariate analysis
      (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and
      XRCC1 399G/G genotypes were associated with short survival in patients receiving
      azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then
      performed an exploratory analysis to evaluate the effect of the simultaneous
      presence of multiple adverse variant genotypes. Interestingly, patients with ?1
      adverse genetic variants had a short survival, independently from their
      International Prognostic Scoring System (IPSS) and therapy received. To our
      knowledge, this is the first study showing that polymorphisms in folate
      metabolizing pathway, DNA synthesis and DNA repair genes could influence survival
      of MDS patients.

PMID- 29205205
TI  - Gene expression and linkage analysis implicate CBLB as a mediator of rituximab
      resistance.
AB  - Elucidating resistance mechanisms for therapeutic monoclonal antibodies (MAbs) is
      challenging, because they are difficult to study in non-human models. We
      therefore developed a strategy to genetically map in vitro drug sensitivity,
      identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20
      MAb that provides significant benefit to patients with B-cell malignancies. We
      discovered novel loci with genome-wide mapping analyses and functionally
      validated one of these genes, CBLB, which causes rituximab resistance when
      knocked down in lymphoma cells. This study demonstrates the utility of genome
      wide mapping to discover novel biological mechanisms of potential clinical
      advantage.

PMID- 29205206
TI  - Applications of pharmacogenomics in regulatory science: a product life cycle
      review.
AB  - With rapid developments of pharmacogenomics (PGx) and regulatory science, it is
      important to understand the current PGx integration in product life cycle, impact
      on clinical practice thus far and opportunities ahead. We conducted a cross
      sectional review on PGx-related regulatory documents and implementation
      guidelines in the United States and Europe. Our review found that although PGx
      related guidance in both markets span across the entire product life cycle, the
      scope of implementation guidelines varies across two continents. Approximately
      one-third of Food and Drug Administration (FDA)-approved drugs with PGx
      information in drug labels and half of the European labels posted on PharmGKB
      website contain recommendations on genetic testing. The drugs affected 19 and 15
      World Health Organization Anatomical Therapeutic Chemical drug classes (fourth
      level) in the United States and Europe, respectively, with protein kinase
      inhibitors (13 drugs in the United States and 16 drugs in Europe) being most
      prevalent. Topics of emerging interest were novel technologies, adaptive design
      in clinical trial and sample collection.

PMID- 29205208
TI  - Relationships between walking velocity and distance and the symmetry of
      temporospatial parameters in chronic post-stroke subjects.
AB  - PURPOSE: Subjects with post-stroke hemiparesis frequently present with asymmetric
      gait patterns. Symmetry, reflecting similarities in temporospatial, kinematic
      parameters, is an important measure of gait assessment. The study was designed to
      examine the relationships between asymmetry of temporal, spatial and kinematic
      gait parameters and walking velocity and distance. METHODS: Temporospatial and
      kinematic gait parameters were examined in a group of 50 chronic post-stroke
      subjects and in a group of 25 healthy controls. Symmetry ratio was calculated for
      all the parameters. Gait velocity was measured during 10-metre test, the walking
      distance during 2-Minute Walk Test, and balance during Up and Go Test. RESULTS:
      The relationship between stance phase duration symmetry and gait speed was at a
      moderate level (r = -0.43, p = 0.0173). There was a moderate relationship between
      swing phase symmetry and walking velocity and distance. The findings did not show
      a significant correlation between step length symmetry versus gait speed and
      distance. CONCLUSIONS: There is a mild relationship between self-selected gait
      velocity and walking distance versus temporal parameters symmetry. The findings
      do not confirm a relationship between self-selected gait velocity and walking
      distance versus spatial and kinematic parameters as well as balance. Likewise, no
      evidence confirms that asymmetry of temporal, spatial, kinematic gait parameters
      changes with the age of post-stroke subjects or is related to the length of time
      from stroke onset. Given the above, gait symmetry may be recognized as an
      important indicator of the level of gait control in post-stroke patients because
      it enables unique gait assessment, independent from other parameters.

PMID- 29205207
TI  - Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma:
      preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and
      primates.
AB  - Translation of drug candidates into clinical settings requires demonstration of
      preclinical efficacy and formal toxicology analysis for filling an
      Investigational New Drug (IND) application with the US Food and Drug
      Administration (FDA). Here, we investigate the membrane-associated glucose
      response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We
      evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis
      targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing
      class of agents. BMTP-78 was validated in cells from patients with acute myeloid
      leukemia and in a panel of human leukemia and lymphoma cell lines, where it
      induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro
      efficacy of BMTP-78, we performed formal good laboratory practice toxicology
      studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and
      rhesus monkeys). These analyses represent required steps towards an IND
      application of BMTP-78 for theranostic first-in-human clinical trials.

PMID- 29205209
TI  - Foot mechanics in young women are altered after walking in high-heeled shoes.
AB  - PURPOSE: Nowadays, fashion has caused that many young women are wearing high
      heeled shoes. Therefore, the aim of this study was to examine the effects of long
      term walking in high-heeled shoes on the foot mechanics during barefoot gait.
      METHODS: Forty-three young women (22 +/- 2.1 years) divided into two groups
      participated in this retrospective cohort study. The first group was composed of
      women who frequently wear high-heeled footwear. The second, infrequent wearers
      group, consisted of women who preferred flat-heeled shoes. Measurements of gait
      parameters were recorded for barefoot gait. A motion analysis system and two
      force plates were used in order to evaluate the lower-limb rocker mechanism,
      transverse foot arch height and parameters of ground reaction force. RESULTS:
      Walking in high-heeled shoes modified barefoot foot mechanics, which manifested
      itself in a shorter duration (by ca. 4%) of the first and second rocker and a
      significantly longer duration (by 5%) of the third rocker phase as well as a
      substantial reduction in height of the transverse foot arch (by around 50%) in
      women habitually walking in high-heeled shoes. A significantly shorter relative
      duration of the third rocker (44.3% of cycle time) and greater value of the
      vertical component of ground reaction force (114.7% BW) in the third rocker phase
      were found in the group of women habitually walking in high-heeled shoes.
      CONCLUSIONS: The mechanism of foot rolling, with flattened foot arch, and
      significantly higher values of the vertical component of ground reaction force
      and shorter time might lead to overload in lowerlimb joints in young women.

PMID- 29205210
TI  - Assessing the asymmetry of free gait in healthy young subjects.
AB  - PURPOSE: The purpose of this study was to derive reference values for a four
      level scale intended to evaluate variation in free gait asymmetry measurements in
      healthy subjects. METHODS: This evaluation is based on kinetic values for the
      left and right lower limbs during gait, registered with advanced measurement
      systems and assessed using the symmetry index (SI) developed by Robinson.
      RESULTS: For the majority of parameters, the SI does not follow normal
      distribution. As such, quartile values were used to create intervals for a four
      step scale of assessing symmetry of free gait in healthy subjects for each gait
      parameter of interest. The SI rating intervals were from 0% (very good symmetry)
      to 21.2% (very poor symmetry) for kinetic parameters. The poorest symmetry was
      observed for horizontal force F3. CONCLUSIONS: The four-step scale of assessing
      symmetry in free gait in healthy subjects can be used in diagnosing gait
      disorders, devising surgical treatment strategies, and monitoring the
      rehabilitation process. Reference values for intervals of symmetry indicators in
      healthy subjects can be used as criteria for comparing individuals with/without
      disabilities.

PMID- 29205211
TI  - A computational evaluation of sedentary lifestyle effects on carotid hemodynamics
      and atherosclerotic events incidence.
AB  - PURPOSE: Hemodynamics has a key role in atheropathogenesis. Indeed,
      atherosclerotic phenomena occur in vessels characterized by complex geometry and
      flow pattern, like the carotid bifurcation. Moreover, lifestyle is a significant
      risk factor. The aim of this study is to evaluate the hemodynamic effects due to
      two sedentary lifestyles - sitting and standing positions - in the carotid
      bifurcation in order to identify the worst condition and to investigate the
      atherosclerosis incidence. METHODS: The computational fluid dynamics (CFD) was
      chosen to carry out the analysis, in which in vivo non-invasive measurements were
      used as boundary conditions. Furthermore, to compare the two conditions, one
      patient-specific 3D model of a carotid bifurcation was reconstructed starting
      from computer tomography. Different mechanical indicators, correlated with
      atherosclerosis incidence, were calculated in addition to flow pattern and
      pressure distribution: the time average wall shear stress (TAWSS), the
      oscillatory shear index (OSI) and the relative residence time (RRT). RESULTS: The
      results showed that the bulb and the external carotid artery emergence are the
      most probable regions in which atherosclerotic events could happen. Indeed, low
      velocity and WSS values, high OSI and, as a consequence, areas with chaotic
      swirling flow, with stasis (high RRT), occur. Moreover, the sitting position is
      the worst condition: considering a cardiac cycle, TAWSS is less than 17.2% and
      OSI and RRT are greater than 17.5% and 21.2%, respectively. CONCLUSIONS: This
      study suggests that if a person spends much time in the sitting position, a high
      risk of plaque formation and, consequently, of stenosis could happen.

PMID- 29205212
TI  - Experimental identification of a mathematical model of human operator working
      under mental stress.
AB  - In engineering the human is considered as one of the system elements. In most
      studies, his/her model remains unchanged due to the external factors. The present
      study shows that a relation between the mental stress and human dynamics cannot
      be neglected. The dynamic characteristics of the operator model change due to
      external stimuli, i.e., mental stress. The aim of this study was to present
      identification of a mathematical human model and measurement methodology of the
      mental stress level. To determine the level of human response to external
      stimuli, the electrocardiography (ECG) and electromyography (EMG) methods were
      applied. The results showed difference in model parameters that cannot be
      neglected during the modeling of the human operator. The present study points to
      the need of developing simplified human models, taking into account external
      stimuli that have direct impact on his/her effectiveness. Some interdisplinary
      investigation provide may benefits combining part of the automation and
      ergonomics research areas.

PMID- 29205213
TI  - Mechanical properties variation and constitutive modelling of biomedical polymers
      after sterilization.
AB  - PURPOSE: In this work, the mechanical behavior of two block copolymers for
      biomedical applications is studied with particular regard to the effects induced
      by a steam sterilization treatment that biomedical devices usually undergo in
      healthcare facilities. This investigation is aimed at describing the elasto
      plastic behavior of the stress-strain response, determining a functional
      dependence between material constitutive parameters, to obtain an optimal
      constitutive model. METHODS: The mechanical properties of these polymers are
      analyzed through uniaxial tensile tests, before and after the sterilization
      process. The effect of sterilization on the mechanical behavior is evaluated. The
      Ramberg-Osgood model is used to describe the elasto-plastic behavior of the
      stress-strain response. RESULTS: Data from uniaxial tensile tests are discussed
      in the light of previous data on the same polymeric materials, in order to
      highlight the correlation between physicochemical and mechanical properties
      variation. The material constitutive parameters are determined and the functional
      dependence between them is found, thus enabling an optimal constitutive model to
      be obtained. CONCLUSIONS: The effect of sterilization on the material
      constitutive parameters is studied, to evaluate the suitability of the model in
      describing the mechanical response of biomedical polymer before and after
      sterilization treatment. The same approach can be applied to other biomaterials,
      under various tensile tests, and for several processes that induce variation in
      mechanical properties.

PMID- 29205214
TI  - Biomechanics of the shoulder girdle: a case study on the effects of union rugby
      tackles.
AB  - PURPOSE: The shoulder girdle is a complex system, comprised by a kinematic chain
      and stabilizers. Due to the delicate equilibrium and synchronism between mobility
      and stability, high external loads may compromise its physiology, increasing the
      risk of injuries. Thus, this study intends to fully characterize the effects of a
      rugby tackle on the shoulder's anatomy and physiology. METHODS: For the
      experimental procedures, a matrix of pressure sensors was used, based on the
      Teckscan(r) pressure in-soles, force plates, an isokinetic dynamometer and sEMG
      (surface electromyography). RESULTS: The anterosuperior region of the shoulder
      girdle confirmed the highest pressure values during impact (100 kPa-200 kPa).
      Also, the right and left feet performed a vertical peak force of 1286 N (1.4 BW)
      and 1998 N (2.21 BW), respectively. The muscular activity of the shoulder muscles
      decreased after performing multiple tackles. CONCLUSIONS: During a tackle, the
      clavicle, scapula, trapezius and acromioclavicular joint are the anatomical
      structures with higher risk of injury. Also, the strike force on the feet
      decreases for stability purposes. After performing multiple impacts the muscular
      activity of the trapezius and rotator cuff muscles decreases, which may lead, in
      the long-term, to instability of the shoulder and inefficiency of the
      scapulohumeral rhythm.

PMID- 29205215
TI  - Symmetry of lower limb loading in healthy adults during normal and abnormal
      stance.
AB  - PURPOSE: The purpose of the research was twofold: (1) to describe the normal
      asymmetry in lower limb loading during a normal stance and during a stance with
      visual and vestibular disturbance relating to the lower limb dominance, (2) to
      assess relations of loading of both lower limbs with body weight and height (BMI)
      and leg functional dominance. METHODS: The subjects of this study were 95
      students. Settings of the two Kistler platforms were used to register the time
      series of the vertical component of the ground reaction force while the subject
      was standing (45 seconds) in a normal position and next with eyes covered with a
      band and head tilted back position with one leg placed on one platform and the
      other on the second platform. The symmetry index (SI) was used to describe the
      asymmetry of the left or right loading. RESULTS: The greater loading of the left
      or right leg during standing was independent of the functional leg dominance. The
      distribution of left and right lower limb loading in both trials may suggest that
      a low asymmetry, less than 5%, is represented by about 30% of subjects in
      general. No significant correlation was found between the SI and BMI of subjects
      who had a normal body weight, but in the group of overweight subjects the
      correlation was very high (r = 0.9). CONCLUSION: The results show that in
      describing norms of asymmetry in posture control in healthy humans it is very
      important to compare the results to posture asymmetry in various injuries or
      diseases. The most important result is that the higher asymmetry of lower limb
      loading is associated with overweight, which implies greater risk to health of
      those people.

PMID- 29205216
TI  - Investigation of blood flow rheology using second-grade viscoelastic model (Phan
      Thien-Tanner) within carotid artery.
AB  - PURPOSE: Hemodynamic factors, such as Wall Shear Stress (WSS), play a substantial
      role in arterial diseases. In the larger arteries, such as the carotid artery,
      interaction between the vessel wall and blood flow affects the distribution of
      hemodynamic factors. The fluid is considered to be non-Newtonian, whose flow is
      governed by the equation of a second-grade viscoelastic fluid and the effects of
      viscoelastic on blood flow in carotid artery is investigated. METHODS: Pulsatile
      flow studies were carried out in a 3D model of carotid artery. The governing
      equations were solved using finite volume C++ based on open source code,
      OpenFOAM. To describe blood flow, conservation of mass and momentum, a
      constitutive relation of simplified Phan-Thien-Tanner (sPTT), and appropriate
      relations were used to explain shear thinning behavior. RESULTS: The first
      recirculation was observed at t = 0.2 s, in deceleration phase. In the
      acceleration phase from t = 0.3 s to t = 0.5 s, vortex and recirculation sizes in
      bulb regions in both ECA and ICA gradually increased. As is observed in the line
      graphs based on extracted data from ICA, at t = 0.2 s, tauyy is the maximum
      amount of wall shear stress and tauxy the minimum one. The maximum shear stress
      occurred in the inner side of the main branch (inner side of ICA and ECA) because
      the velocity of blood flow in the inner side of the bulb region was maximum due
      to the created recirculation zone in the opposite side in this area. CONCLUSIONS:
      The rheology of blood flow and shear stress in various important parts (the area
      that are in higher rates of WSS such as bifurcation region and the regions after
      bulb areas in both branches, Line1-4 in Fig. 7) were also analyzed. The
      investigation of velocity stream line, velocity profile and shear stress in
      various sections of carotid artery showed that the maximum shear stress occurred
      in acceleration phase and in the bifurcation region between ECA and ICA which is
      due to velocity gradients and changes in thinning behavior of blood and
      increasing strain rate in Newtonian stress part.

PMID- 29205217
TI  - Analysis of upper limb muscle strength in the early phase of brain stroke.
AB  - PURPOSE: The aim of this study was to determine the muscles with the lowest
      strength in non-affected (non-A) and affected upper limb (A), to assess
      differences between men and women and to correlate these values with age in
      patients after stroke. METHODS: Sixty patients (40 male, 20 female), hospitalized
      in Neurorehabilitation Ward, 1-2 weeks after stroke, were included in the study.
      Their age ranged from 50 to 80 years with a mean (sd) of 65.5 (18.7) years.
      Muscle force values from upper limb muscles were measured using the MicroFet 2
      hand-held dynamometer. The results are given in Newtons [N], mean values of
      muscular force, effect sizes and confidence intervals are displayed as Cohen's d
      and 95% CI were determined. Moreover, we made the coefficients correlation for
      differences in muscular force versus the Rivermead Motor Assessment (RMA) arm
      section. RESULTS: Strength of (A) upper limb in comparison to (non-A) was 39%
      weaker. The severely affected muscle groups were the shoulder flexion 41% (women)
      versus 46% (men); elbow flexion 39% (women) versus 31% (men); wrist extension 36%
      (women) versus 42% (men). No significant correlations were found between muscle
      strength results and RMA or age. CONCLUSIONS: Muscle force of (A) upper limb
      after stroke demonstrates a 39% decrease. Men show more significant decrease than
      women (40% vs. 35%). Functional assessment in RMA values shows the better results
      in women (4.9 +/- 4.1) than men (3.4 +/- 3.2).

PMID- 29205218
TI  - A longitudinal assessment of myoelectric activity, postural sway, and low-back
      pain during pregnancy.
AB  - PURPOSE: The present study aimed at investigating the control of upright quiet
      standing in pregnant women throughout pregnancy, and whether low-back pain exerts
      influence on this motor task. METHODS: Myoelectric signals from postural muscles
      and stabilometric data were collected from 15 non-pregnant and 15 pregnant women
      during upright quiet standing. Electromyogram envelopes and center of pressure
      metrics were evaluated in the control group, as well as in pregnant women in
      their first and third trimester of pregnancy. A correlation analysis was
      performed between the measured variables and a low-back pain disability index.
      RESULTS: Pregnant women exhibited a decreased maximum voluntary isometric
      activity for all postural muscles evaluated. Additionally, the activity of lumbar
      muscles during the postural task was significantly higher in the pregnant women
      in comparison to the non-pregnant controls. The soleus muscle maintained its
      activity at the same level as the gestation progressed. Higher postural
      oscillations were observed in the anteroposterior direction while mediolateral
      sway was reduced in the third trimester of pregnancy. No correlation was detected
      between the lowback pain disability index and neuromechanical variables.
      CONCLUSION: This study provides additional data regarding the functioning and
      adaptations of the postural control system during pregnancy. Also, we provide
      further evidence that postural control during quiet standing cannot be used to
      predict the occurrence of low-back pain. We hypothesize that the modifications in
      the neural drive to the muscles, as well as in postural sway may be related to
      changes in the biomechanics and hormonal levels experienced by the pregnant
      women.

PMID- 29205219
TI  - Experimental analysis of insertion torques and forces of threaded and press-fit
      acetabular cups by means of ex vivo and in vivo measurements.
AB  - PURPOSE: In THA a sufficient primary implant stability is the precondition for
      successful secondary stability. Industrial foams of different densities have been
      used for primary stability investigations. The aim of this study was to analyse
      and compare the insertion behaviour of threaded and press-fit cups in vivo and ex
      vivo using bone substitutes with various densities. METHODS: Two threaded (Bicon
      Plus(r), Trident(r) TC) and one press-fit cup (Trident PSL(r)) were inserted by
      orthopaedic surgeons (S1, S2) into 10, 20 and 31 pcf blocks, using modified
      surgical instruments allowing measurements of the insertion forces and torques.
      Furthermore, the insertion behaviour of two cups were analysed intraoperatively.
      RESULTS: Torques for the threaded cups increased while bone substitute density
      increased. Maximum insertion torques were observed for S2 with 102 Nm for the
      Bicon Plus(r) in 20 pcf blocks and 77 Nm for the Trident(r) TC in 31 pcf blocks,
      which compares to the in vivo measurement (85 Nm). The average insertion forces
      for the press-fit cup varied from 5.2 to 6.8 kN (S1) and 7.2-11.5 kN (S2) ex
      vivo. Intraoperatively an average insertion force of 8.0 kN was determined.
      CONCLUSIONS: Implantation behaviour was influenced by acetabular cup design, bone
      substitute and experience of the surgeon. No specific density of bone substitute
      could be favoured for ex vivo investigations on the implantation behaviour of
      acetabular cups. The use synthetic bone blocks of high density (31 pcf) led to
      problems regarding cup orientation and seating. Therefore, bone substitutes used
      should be critically scrutinized in terms of the comparability to the in vivo
      situation.

PMID- 29205220
TI  - Influence of modified muscle morphology and activity pattern on the results of
      musculoskeletal system modelling in cerebral palsy patient.
AB  - PURPOSE: The aim of the present study was to evaluate the influence of modified
      morphological parameters of the muscle model and excitation pattern on the
      results of musculoskeletal system numerical simulation in a cerebral palsy
      patient. METHODS: The modelling of the musculoskeletal system was performed in
      the AnyBody Modelling System. The standard model (MoCap) was subjected to
      modifications consisting of changes in morphological parameters and excitation
      patterns of selected muscles. The research was conducted with the use of data of
      a 14-year-old cerebral palsy patient. RESULTS: A reduction of morphological
      parameters (variant MI) caused a decrease in the value of active force generated
      by the muscle with changed geometry, and as a consequence the changes in active
      force generated by other muscles. A simulation of the abnormal excitation pattern
      (variant MII) resulted in the muscle's additional activity during its
      lengthening. The simultaneous modification of the muscle morphology and
      excitation pattern (variant MIII) points to the interdependence of both types of
      muscle model changes. A significant increase in the value of the reaction force
      in the hip joint was observed as a consequence of modification of the hip
      abductor activity. CONCLUSIONS: The morphological parameters and the excitation
      pattern of modelled muscles have a significant influence on the results of
      numerical simulation of the musculoskeletal system functioning.

PMID- 29205221
TI  - Experimental study and modelling the evolution of viscoelastic hysteresis loop at
      different frequencies in myocardial tissue.
AB  - Our work involved experimental study of the influence of actomyosin complexes and
      the main structural components of the myocardial tissue - connective tissue
      collagen framework and cardiomyocytes - on the characteristics of viscoelastic
      hysteresis at different frequencies. In this paper a new method was introduced
      for the analysis of the viscoelastic characteristics of the force hysteresis in
      the isolated myocardial preparation for the assessment of mechanical energy
      expenditure in the tension-compression cycle. We established that basic
      myocardial structures have an impact on the to the characteristics of the
      viscoelastic hysteresis in many ways. It was shown that in rat's myocardium
      cardiomyocytes one main factor that define the stiffness and viscosity of the
      myocardium in the physiological range of deformations, while binding of calcium
      ions with EGTA and calcium removal of sarcoplasmic reticulum with caffeine
      reduces viscoelasticity by ~30% and collagen framework is responsible for about
      10% of viscoelasticity. It was revealed that in the physiological range of the
      hysteresis frequencies (3 to 7 Hz) expenditure of mechanical energy per unit of
      time increases linearly with increasing frequency. We proposed the structural and
      functional model that adequately describes the characteristics of the
      viscoelastic hysteresis in myocardial preparation in the range of strains and
      frequencies being under study.

PMID- 29205222
TI  - Relationship between the mineral content of human trabecular bone and selected
      parameters determined from fatigue test at stepwise-increasing amplitude.
AB  - PURPOSE: The study aimed to investigate a relationship between the mineral
      content of human trabecular bone and parameters determined from compression
      fatigue tests at stepwise-increasing amplitude. METHODS: Mineral content of
      trabecular bone was estimated comparing density and bone mineral density values.
      The relationship between the ash density, bone mineral density and factors
      obtained from fatigue test: fatigue life, cumulative elastic energy and
      cumulative energy of dissipation was determined. RESULTS: The results from the
      measurements of ash density and bone mineral density show good correlation with
      the fatigue test results. The relationship was estimated based on the correlation
      coefficient R within 0.74-0.79 for the particular pairs of factors. CONCLUSIONS:
      The study shows that the ash density and the bone mineral density are good
      predictors to estimate the fatigue life of trabecular bone. The study also
      validates the applicability of the tests at stepwise-increasing amplitude in
      determining the mechanical properties of trabecular bone.

PMID- 29205223
TI  - Investigation of chest injury mechanism caused by different seatbelt loads in
      frontal impact.
AB  - PURPOSE: The purpose of this quantitative study is to investigate the differences
      of the injury mechanism caused by two different types of seatbelt loads on the
      occupant's chest. METHODS: The finite element analysis is employed to compare the
      different responses of the human body model, including comparison of kinematics,
      chest accelerations, seatbelt forces and chest injury outcomes regarding chest
      deflections and rib fractures. RESULTS: The calculated rib strain-stress response
      from simulations in force-limiting seatbelt are higher than that in the regular
      seatbelt. The forward movement and torso twist are both great in simulations with
      force-limiting seatbelt. Moreover, there are obvious differences in the injury
      outcomes of chest deflections and rib fracture risks under the different seatbelt
      loads. CONCLUSION: Results indicate that the chest deflections and rib fracture
      risks are negatively correlated under the load of the force-limiting seatbelt,
      However, they are positively correlated to and determined by the seatbelt peak
      load of the regular seatbelt. This paper can provide a reference for study of the
      chest injury mechanism and protection efficiency of seatbelt.

PMID- 29205224
TI  - Influence of changing frequency and various sceneries on stabilometric parameters
      and on the effect of adaptation in an immersive 3D virtual environment.
AB  - PURPOSE: The aim of the study was to examine the influence of different types of
      virtual sceneries and frequencies of movement of visual disturbances on
      stabilometric values as well as whether individual sceneries and changing
      frequency can minimize effect of adaptation of tested person to applied
      disturbances. METHODS: There were 23 healthy participants. A person has been
      standing on a Zebris stabilometric platform. Virtual 3D environment was displayed
      by means of HMD Oculus Rift system. An open (a meadow) and closed (a room)
      sceneries were used. The sceneries moved along the sagittal axis and rotated
      around horizontal axis. The measurement lasted 30 seconds and in the middle of it
      frequency of translational movement was changed from 0.7 Hz to 1.4 Hz or from 1.4
      Hz to 0.7 Hz. RESULTS: The data were reported as medians of COP velocity and
      ellipse area. Visual disturbances caused the increase of these values in
      comparison with the tests conducted with open eyes. Results divided into periods
      (the first and the second 15 seconds) showed that in the first half of the test
      values were higher compared to the second half. The comparison of values obtained
      for open and closed scenery showed that higher values were recorded for open
      scenery. CONCLUSIONS: The comparison of both types of sceneries on the basis of
      COP velocity and ellipse area showed that open scenery had a greater impact on
      the measured stabilometric values. It was found out as well that people got
      accustomed to the applied disturbances, but this effect was lower in the open
      scenery.

PMID- 29205225
TI  - Using the discrete wavelet transform in assessing the effectiveness of
      rehabilitation in patients after ACL reconstruction.
AB  - PURPOSE: The purpose of the current study was to assess the effectiveness of
      rehabilitation in patients after anterior cruciate ligament reconstruction (ACLR)
      using a wavelet analysis of the torque-time curve patterns of the extensors of
      the affected knee. The analysis aimed at the quantitative evaluation of
      irregularities in these torque-time patterns. METHODS: The study involved a group
      of 22 men who had had ACL reconstruction. The torque-time characteristics were
      recorded 3, 6 and 12 months after the surgery by an isokinetic dynamometer. They
      were then examined using the orthogonal Daubechies 4 (Db 4) and biorthogonal Bior
      3.1 wavelets. RESULTS: A statistical analysis of the results revealed significant
      differences in values of the high-frequency energy stored in the details of the
      signal from the dynamometer between the first and last measurements, both for the
      Db 4 ( p <= 0.023) and Bior 3.1 ( p <= 0.01) wavelets. These differences were
      found in 73% of patients whose curve patterns were analysed using the Db 4
      wavelet and in 82% of patients in the case of the Bior 3.1 wavelet. CONCLUSIONS:
      The wavelet transform proved to be an effective research tool in the qualitative
      evaluation of irregularities occurring in the curve patterns of the torque
      generated by the extensors of the ACL reconstructed knee. The findings of the
      study suggest that time-frequency analyses of these characteristics can be of
      practical importance, as they help assess the state of the patient's knee joint
      and his progress in rehabilitation after ACLR.

PMID- 29205226
TI  - Is bearing resistance negligible during wheelchair locomotion? Design and
      validation of a testing device.
AB  - PURPOSE: Among the different resistances occurring during wheelchair locomotion
      and that limit the user autonomy, bearing resistance is generally neglected,
      based on a few studies carried out in static conditions and by manufacturer's
      assertion. Therefore, no special attention is generally paid to the mounting and
      the maintenance of manual wheelchair bearings. However, the effect of inadequate
      mounting or maintenance on wheelchair bearing resistance has still to be
      clarified. This study aimed at filling this gap by developing and validating a
      specific device allowing the measurement of wheelchair bearing friction,
      characterized by low speed velocities, with an accuracy lower than 0.003 Nm.
      METHODS: The bearing resistance measured by the device was compared to free
      deceleration measurement, intra and inter operator reproducibility were assessed.
      A factorial experiment allowed the effects of various functioning parameters
      (axial and radial loads, velocity) to be classified. RESULTS: The device allowed
      significant differences in the bearing resistance of static and rotating
      conditions to be measured, even if a relatively high proportionality was found
      between both conditions. The factorial experiment allowed the expected impact of
      the radial load on bearing resistance as well as the predominant effect of the
      axial load to be demonstrated. CONCLUSIONS: As a consequence, it appeared that
      the control of the axial load is compulsory for measurement purposes or during
      wheel mounting, to avoid significant increase of global resistance during
      wheelchair locomotion. The findings of this study could help enhancing the models
      which assess manual wheelchair mechanical power from its settings and use
      conditions.

PMID- 29205227
TI  - Digital image correlation techniques for strain measurement in a variety of
      biomechanical test models.
AB  - PURPOSE: Previous biomechanical studies have estimated the strains of bone and
      bone substitutes using strain gages. However, applying strain gages to biological
      samples can be difficult, and data collection is limited to a small area under
      the strain gage. The purpose of this study was to compare digital image
      correlation (DIC) strain measurements to those obtained from strain gages in
      order to assess the applicability of DIC technology to common biomechanical
      testing scenarios. METHODS: Compression and bending tests were conducted on
      aluminum alloy, polyurethane foam, and laminated polyurethane foam specimens.
      Simplified single-legged stance loads were applied to composite and cadaveric
      femurs. RESULTS: Results showed no significant differences in principal strain
      values (or variances) between strain gage and DIC measurements on the aluminum
      alloy and laminated polyurethane foam specimens. There were significant
      differences between the principal strain measurements of the non-laminated
      polyurethane foam specimens, but the deviation from theoretical results was
      similar for both measurement techniques. DIC and strain gage data matched well in
      83.3% of all measurements in composite femur models and in 58.3% of data points
      in cadaveric specimens. Increased variation in cadaveric data was expected, and
      is associated with the well-documented variability of strain gage analysis on
      hard tissues as a function of bone temperature, hydration, gage protection, and
      other factors specific to cadaveric biomechanical testing. CONCLUSIONS: DIC
      techniques provide similar results to those obtained from strain gages across
      standard and anatomical specimens while providing the advantages of reduced
      specimen preparation time and full-field data analysis.

PMID- 29205228
TI  - Repression of YdaS Toxin Is Mediated by Transcriptional Repressor RacR in the
      Cryptic rac Prophage of Escherichia coli K-12.
AB  - Horizontal gene transfer is a major driving force behind the genomic diversity
      seen in prokaryotes. The cryptic rac prophage in Escherichia coli K-12 carries
      the gene for a putative transcription factor RacR, whose deletion is lethal. We
      have shown that the essentiality of racR in E. coli K-12 is attributed to its
      role in transcriptionally repressing toxin gene(s) called ydaS and ydaT, which
      are adjacent to and coded divergently to racR. IMPORTANCE Transcription factors
      in the bacterium E. coli are rarely essential, and when they are essential, they
      are largely toxin-antitoxin systems. While studying transcription factors encoded
      in horizontally acquired regions in E. coli, we realized that the protein RacR, a
      putative transcription factor encoded by a gene on the rac prophage, is an
      essential protein. Here, using genetics, biochemistry, and bioinformatics, we
      show that its essentiality derives from its role as a transcriptional repressor
      of the ydaS and ydaT genes, whose products are toxic to the cell. Unlike type II
      toxin-antitoxin systems in which transcriptional regulation involves complexes of
      the toxin and antitoxin, repression by RacR is sufficient to keep ydaS
      transcriptionally silent.

PMID- 29205229
TI  - CRISPR-Cas-Mediated Gene Silencing Reveals RacR To Be a Negative Regulator of
      YdaS and YdaT Toxins in Escherichia coli K-12.
AB  - Bacterial genomes are rich in horizontally acquired prophages. racR is an
      essential gene located in the rac prophage that is resident in many Escherichia
      coli genomes. Employing a clustered regularly interspaced short palindromic
      repeat (CRISPR)-Cas-based gene silencing approach, we show that RacR is a
      negative regulator of the divergently transcribed and adjacent ydaS-ydaT operon
      in Escherichia coli K-12. Overexpression of YdaS and YdaT due to RacR depletion
      leads to cell division defects and decrease in survival. We further show that
      both YdaS and YdaT can act independently as toxins and that RacR serves to
      counteract the toxicity by tightly downregulating the expression of these toxins.
      IMPORTANCEracR is an essential gene and one of the many poorly studied genes
      found on the rac prophage element that is present in many Escherichia coli
      genomes. Employing a CRISPR-based approach, we have silenced racR expression to
      various levels and elucidated its physiological consequences. We show that the
      downregulation of racR leads to upregulation of the adjacent ydaS-ydaT operon.
      Both YdaS and YdaT act as toxins by perturbing the cell division resulting in
      enhanced cell killing. This work establishes a physiological role for RacR, which
      is to keep the toxic effects of YdaS and YdaT in check and promote cell survival.
      We, thus, provide a rationale for the essentiality of racR in Escherichia coli K
      12 strains.

PMID- 29205230
TI  - Can Protein Restriction Set Up T Lymphocytes Favorably For Their Activation
      Against Pathogens Through Myc?
AB  - One area that presents a significant threat to global health is infectious
      diseases. With increasing prevalence of antibiotic-resistant bacteria [1],
      opportunistic infections are a growing concern for human societies. In 2009,
      there were 89,000 deaths caused by pneumonia, septicemia, and influenza virus in
      the United States alone [2]. Antibiotic-resistant bacteria increase the risk of
      secondary infection that is associated with many standard medical procedures such
      as organ transplantation, chemotherapy, dialysis, and elective surgery [1]. The
      deceleration of new drug discovery suggests that acute preventative strategies
      strengthening host immunity prior to such procedures are of strong interest. In
      this mini review, I will suggest a protein restriction-Myc signaling as a
      potential pharmacological target to boost the survival outcome following
      pathogenic bacterial infection.

PMID- 29205231
TI  - Erratum to: Moving from medical to health systems classifications of deaths:
      extending verbal autopsy to collect information on the circumstances of
      mortality.
AB  - [This corrects the article DOI: 10.1186/s41256-016-0002-y.].

PMID- 29205237
TI  - Pillararene-based fluorescent chemosensors: recent advances and perspectives.
AB  - In 2008, a new class of pillar-shaped supramolecular macrocyclic hosts was
      reported, known as "pillararenes". Their particular electron-rich cavity and the
      ease of their functionalization offer possibilities for the design and synthesis
      of novel fluorescent chemosensors. Subsequently, pillararene-based fluorescent
      sensors and probes have been rapidly developed. This feature article covers the
      most recent contributions from the pillararene-based fluorescent sensor field in
      terms of anion/cation sensing, small molecule recognition, biomolecule detection,
      fluorescent supramolecular aggregates, and biomedical imaging. Meanwhile, we hope
      that this feature article will inspire more effort to be devoted to this emerging
      field.

PMID- 29205232
TI  - Erratum to: Volume 1, Contraception and Reproductive Medicine.
AB  - [This corrects the article DOI: 10.1186/s40834-016-0016-3.][This corrects the
      article DOI: 10.1186/s40834-016-0011-8.][This corrects the article DOI:
      10.1186/s40834-016-0009-2.][This corrects the article DOI: 10.1186/s40834-016
      0010-9.][This corrects the article DOI: 10.1186/s40834-016-0008-3.].

PMID- 29205238
TI  - The role of the sigma-holes in stability of non-bonded chalcogenidebenzene
      interactions: the ground and excited states.
AB  - The stability of the T-shaped and stacked complexes of benzene with methanethial
      (CH2S) and methaneselone (CH2Se) and their difluoro-, dichloro-, dibromo
      derivatives is investigated in their ground and first electronic excited states
      by means of the SCS-ADC2 method. The origin of the stabilization in the ground
      state is discussed based on the results of calculations performed using the DFT
      SAPT method. Calculations show that the stability of the T-shaped conformers
      increases upon electronic excitation, while it decreases for most of the stacked
      conformers. Both effects are explained by the changes in the electrostatic
      potential (ESP) of isolated monomers upon the electronic excitation.

PMID- 29205239
TI  - Role of surface oxidation on the size dependent mechanical properties of nickel
      nanowires: a ReaxFF molecular dynamics study.
AB  - Highly reactive metallic nickel (Ni) is readily oxidized by oxygen (O2) molecules
      even at low temperatures. The presence of the naturally resulting pre-oxide shell
      layer on metallic Ni nano materials such as Ni nanowires (NW) is responsible for
      degrading the deformation mechanisms and related mechanical properties. However,
      the role of the pre-oxide shell layer on the metallic Ni NW coupled with the
      complicated mechanical deformation mechanism and related properties have not yet
      been fully and independently understood. For this reason, the ReaxFF reactive
      force field for Ni/O interactions was used to investigate the effect of surface
      oxide layers and the size-dependent mechanical properties of Ni NWs under
      precisely controlled tensile loading conditions. To directly quantify the size
      dependent surface oxidation effect on the tensile mechanical deformation
      behaviour and related properties for Ni NWs, first, ReaxFF-molecular dynamics
      (MD) simulations were carried out to study the oxidation kinetics on the free
      surface of Ni NWs in a molecular O2 environment as a function of various
      diameters (D = 5.0, 6.5, and 8.0 nm) of the NWs, but at the same length. Single
      crystalline, pure metallic Ni NWs were also studied as a reference. The results
      of the oxidation simulations indicate that a surface oxide shell layer with
      limiting thickness of ~1.0 nm was formed on the free surface of the bare Ni NW,
      typically via dissociation of the O-O bonds and the subsequent formation of Ni-O
      bonds. Furthermore, we investigated the evolution of the size-dependent intrinsic
      mechanical elastic properties of the core-oxide shell (Ni/NixOy) NWs by comparing
      them with their un-oxidized counterparts under constant uniaxial tensile loading.
      We found that the oxide shell layer significantly decreases the mechanical
      properties of metallic Ni NW as well as facilitates the initiation of plastic
      deformation as a function of decreasing diameter. The disordered oxide shell
      layer on the Ni NW's surface remarkably reduces the yield stress and Young's
      modulus, due to the increased softening effects with the decreasing NW diameter,
      compared to un-oxidized counterparts. Moreover, the onset of plastic deformation
      occurs at a relatively low yielding strain and stress level for the smaller
      diameter of oxide-coated Ni NWs in comparison to their pure counterparts.
      Furthermore, for pure Ni NWs, Young's modulus, the yielding stress and strain
      slightly decrease with the decrease in the diameter size of Ni NWs.

PMID- 29205240
TI  - Impact of bi-axial strain on the structural, electronic and optical properties of
      photo-catalytic bulk bismuth oxyhalides.
AB  - The structural, electronic and optical properties of bulk bismuth oxyhalides,
      BiOX (X = F, Cl, Br, and I), were studied using state-of-the-art density
      functional theory (DFT)-based calculations. The effects of compressive and
      tensile strains on the in-plane lattice parameters were analyzed to better
      understand their good performance in photo-catalytic applications. Our present
      first-principles calculations show that at least 4% in-plane bi-axial compressive
      strain over the experimental lattice parameters of BiOF is needed for phonon
      stability of this material, whereas other BiOX systems can accept up to 2% in
      plane bi-axial compressive strain and retain their dynamical stability. On the
      other hand, 2% in-plane tensile strain breaks the structural stability of all
      bulk BiOX structures. Tuning the electronic band structures with such external
      compressive strain indeed helps to enhance the separation of charge carriers due
      to larger electron-hole effective mass differences in the BiOBr and BiOI
      structures. The optical properties are discussed from their calculated absorption
      spectra and optical conductivity within independent particle approximations. The
      average values of the calculated optical band gaps are in the range of 3.8-3.9
      eV, 3.3-3.4 eV, 2.7-2.8 eV and 1.7-1.8 eV for the unstrained and compressive
      strained structures, respectively, of the BiOF, BiOCl, BiOBr and BiOI materials,
      which are reasonably good compared to their known experimental ultra-violet
      visible spectroscopy measured data.

PMID- 29205241
TI  - Exploration of H2 binding to the [NiFe]-hydrogenase active site with
      multiconfigurational density functional theory.
AB  - The combination of density functional theory (DFT) with a multiconfigurational
      wave function is an efficient way to include dynamical correlation in
      calculations with multiconfiguration self-consistent field wave functions. These
      methods can potentially be employed to elucidate reaction mechanisms in bio
      inorganic chemistry, where many other methods become either too computationally
      expensive or too inaccurate. In this paper, a complete active space (CAS) short
      range DFT (CAS-srDFT) hybrid was employed to investigate a bio-inorganic system,
      namely H2 binding to the active site of [NiFe] hydrogenase. This system was
      previously investigated with coupled-cluster (CC) and multiconfigurational
      methods in the form of cumulant-approximated second-order perturbation theory,
      based on the density matrix renormalization group (DMRG). We find that it is more
      favorable for H2 to bind to Ni than to Fe, in agreement with previous CC and DMRG
      calculations. The accuracy of CAS-srDFT is comparable to both CC and DMRG,
      despite much smaller active spaces were employed than in the corresponding DMRG
      calculations. This enhanced efficiency at the smaller active spaces shows that
      CAS-srDFT can become a useful method for bio-inorganic chemistry.

PMID- 29205243
TI  - Fluorescence quenching of the N-methylquinolinium cation by pairs of water or
      alcohol molecules.
AB  - N-Methylquinolinium cation (MQ+) in its first-excited singlet state is a strong
      oxidant commonly used as a photosensitizer, whose fluorescence is therefore
      quenched by electron donors. Interestingly, the fluorescence of MQ+ is also
      quenched by hydroxy compounds such as water and alcohols, more difficult to
      oxidize. We investigated the quenching mechanism of MQ+ fluorescence by small
      amounts of water and alcohols in acetonitrile solution. The fluorescence
      intensities and lifetimes exhibited a nonlinear dependence on the quencher
      concentration. We found evidence that emissive exciplexes MQ+*-ROH are formed
      between the excited quinolinium and the hydroxy compounds. An accurate
      quantitative description of the results was obtained with a model in which the
      exciplex reacts with a second molecule of the hydroxy compound, which quenches
      the fluorescence. The rate constant of this process increased as the quencher
      ionization energy decreased. We showed also that a low basicity of the hydroxy
      compound inhibits the quenching process. These results are consistent with the
      existence of a concerted photoinduced proton-coupled electron transfer (PCET)
      involving an intermediate complex of the excited quinolinium with a H-bonded
      molecular pair of the hydroxy compounds. In these pairs, a water or an alcohol
      molecule is able to donate an electron to the photoexcited quinolinium cation and
      a proton to the second H-bonded hydroxy molecule, showing an enhanced reducing
      power in comparison with the isolated molecule. The structure of the intermediate
      complex was investigated using high-level quantum mechanical calculations. At
      high water concentrations in acetonitrile/water mixtures, the quenching process
      is slowed down, indicating that higher water aggregates are less effective for a
      PCET process. The results obtained may be relevant to the study of water
      oxidation and electron transfer in biological systems.

PMID- 29205242
TI  - Refining tools to bridge the gap between academia and chemical regulation:
      perspectives for WikiREACH.
AB  - Regulatory hazard and risk assessments of chemical substances have to include all
      reliable and relevant data to be credible and complete. However, screening the
      literature for appropriate studies and extracting data is burdensome. Therefore,
      reducing impediments by making data easily and readily accessible to risk
      assessors could result in more comprehensive hazard and risk assessments. In this
      paper, we study WikiPharma, a database that aggregates ecotoxicity data for
      pharmaceuticals, extracted from peer-reviewed studies. The use of the WikiPharma
      database is explored to develop strategies on how similar tools can bridge
      between science and policy by providing risk assessors with easily accessible
      summary data. Specifically, adapting the concept of WikiPharma to industrial
      chemicals regulated under the REACH regulation is discussed. Experiences with
      WikiPharma show that there is interest in using peer-reviewed studies in
      regulatory decision-making. However, tools like WikiPharma require constant
      updates. Hence, as for "WikiREACH", effective incentives are needed to motivate
      researchers to feed in relevant data for regulatory assessments. Besides, support
      by automated processes can aid in the labour-intensive activity of gathering
      data. To ensure that such a tool is continuously maintained and compatible with
      the regulatory system, and thereby useful for hazard and risk assessments of
      chemicals, it would benefit from being developed in collaboration with the major
      stakeholders in the field, i.e. regulatory agencies, academia, industry,
      scientific journals, and providers of research network platforms.

PMID- 29205244
TI  - Synchronous magnetic control of water droplets in bulk ferrofluid.
AB  - We present a microfluidic platform for magnetic manipulation of water droplets
      immersed in bulk oil-based ferrofluid. Although non-magnetic, the droplets are
      exclusively controlled by magnetic fields without any pressure-driven flow. The
      fluids are dispensed in a sub-millimeter Hele-Shaw chamber that includes
      permalloy tracks on its substrate. An in-plane rotating magnetic field magnetizes
      the permalloy tracks, producing local magnetic gradients, while an orthogonal
      magnetic field magnetizes the bulk ferrofluid. To minimize the magnetostatic
      energy of the system, the water droplets are attracted towards the locations on
      the tracks where the bulk ferrofluid is repelled. Using this technique, we
      demonstrate synchronous generation and propagation of water droplets, study the
      kinematics of propagation, and analyze the flow of the bulk ferrofluid. In
      addition, we show controlled break-up of droplets and droplet-to-droplet
      interactions. Finally, we discuss future applications owing to the potential
      biocompatibility of the droplets.

PMID- 29205249
TI  - Healthybrains.org: From Registry to Randomization.

PMID- 29205250
TI  - Integrating Information from FDG - and Amyloid PET for Detecting Different Types
      of Dementia in Older Persons. A Case-series Study.
AB  - A significant progress has been made in the understanding of the neurobiology of
      Alzheimer's disease. The post-mortem studies are the gold standard for a correct
      histopathological diagnosis, contributing to clarify the correlation with
      cognitive, behavioral and extra-cognitive domains. However, the relationship
      between pathological staging and clinical involvement remains challenging.
      Neuroimaging, including positron emission tomography (PET) and magnetic
      resonance, could help to bridge the gap by providing in vivo information about
      disease staging. In the last decade, advances in the sensitivity of neuroimaging
      techniques have been described, in order to accurately distinguish AD from other
      causes of dementia. Fluorodeoxyglucose-traced PET (FDG-PET) is able to measure
      cerebral metabolic rates of glucose, a proxy for neuronal activity, theoretically
      allowing detection of AD. Many studies have shown that this technique could be
      used in early AD, where reduced metabolic activity correlates with disease
      progression and predicts histopathological diagnosis. More recently, molecular
      imaging has made possible to detect brain deposition of histopathology-confirmed
      neuritic beta-amyloid plaques (Abeta) using PET. Although Abeta plaques are one
      of the defining pathological features of AD, elevated levels of Abeta can be
      detected with this technique also in older individuals without dementia. This
      raises doubts on the utility of Abeta PET to identify persons at high risk of
      developing AD. In the present case-series, we sought to combine metabolic
      information (from FDG-PET) and amyloid plaque load (from Abeta PET) in order to
      correctly distinguish AD from other forms of dementia. By selecting patients with
      Abeta PET + / FDG-PET + and Abeta PET - / FDG-PET +, we propose an integrated
      algorithm of clinical and molecular imaging information to better define type of
      dementia in older persons.

PMID- 29205251
TI  - A Personalized 12-week "Brain Fitness Program" for Improving Cognitive Function
      and Increasing the Volume of Hippocampus in Elderly with Mild Cognitive
      Impairment.
AB  - Reducing cognitive decline in patients with Mild Cognitive Impairment (MCI) may
      slow their progression to develop dementia. In this 12-week single-arm
      intervention trial, elderly patients (n = 127, age 70.69 +/-10.53, 63% female)
      with a diagnosis of MCI were enrolled in a multi-disciplinary Brain Fitness
      Program. The main outcome measure was changes in a battery of 10 cognitive
      domains. Each patient received weekly personalized cognitive stimulation,
      neurofeedback training, and brain coaching/counseling for eating a Mediterranean
      diet, taking omega-3 supplements, increasing fitness, and practicing mindfulness
      meditation. The post-program testing showed 84% of the patients experienced
      statistically significant improvements in their cognitive function (p< 0.05).
      Among the random sample of 17 patients who had a post-program quantitative MRI,
      12 patients had either no atrophy or an actual growth above the baseline volume
      of their hippocampus. These preliminary findings support the concept that a
      personalized Brain Fitness Program can improve cognitive function and either
      reverse or grow the volume of hippocampus in elderly with MCI.

PMID- 29205252
TI  - Correlation between Cognition and Function across the Spectrum of Alzheimer's
      Disease.
AB  - BACKGROUND: Both cognitive and functional deterioration are characteristic of the
      clinical progression of Alzheimer's disease (AD). OBJECTIVES: To systematically
      assess correlations between widely used measures of cognition and function across
      the spectrum of AD. DESIGN: Spearman rank correlations were calculated for
      cognitive and functional measures across datasets from various AD patient
      populations. SETTING: Post-hoc analysis from existing databases. PARTICIPANTS:
      Pooled data from placebo-treated patients with mild (MMSE score >=20 and <=26)
      and moderate (MMSE score >=16 and <=19) AD dementia from two Phase 3 solanezumab
      (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild
      cognitive impairment (LMCI) and mild AD patients from the Alzheimer's Disease
      Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any):
      Placebo (EXPEDITION/2 and IDENTITY/2 subjects). MEASUREMENTS: Cognitive and
      functional abilities were measured in all datasets. Data were collected at
      baseline and every three months for 18 months in EXPEDITION and IDENTITY studies;
      and at baseline, 6, 12, and 24 months in the ADNI dataset. RESULTS: The
      relationship of cognition and function became stronger over time as AD patients
      progressed from preclinical to moderate dementia disease stages, with the
      magnitude of correlations dependent on disease stage and the complexity of
      functional task. The correlations were minimal in the normal control population,
      but became stronger with disease progression. CONCLUSIONS: This analysis found
      that measures of cognition and function become more strongly correlated with
      disease progression from preclinical to moderate dementia across multiple
      datasets. These findings improve the understanding of the relationship between
      cognitive and functional clinical measures during the course of AD progression
      and how cognition and function measures relate to each other in AD clinical
      trials.

PMID- 29205253
TI  - Effects of Computerized Cognitive Training on Gait Speed in Community Dwelling
      Older Adults, A Pilot Study.
AB  - BACKGROUND: In older adults declines in gait speed have been identified as
      predictors of functional decline and have been found in those with cognitive
      dysfunction. Cognitive training interventions that emphasize addressing executive
      function (EF) have resulted in a transfer effect from training cognitive
      processes into improved function. However research examining the effects of an EF
      specific computerized cognitive training (CCT) program on gait speed (GS) is
      limited. OBJECTIVES: To compare the effects of a six week EF specific CCT program
      on GS in community dwelling older adults using a pretest/posttest experimental
      design with subgroup comparisons based on a cutoff GS of 1.0m/s. SETTING: Home
      based. PARTICIPANTS: Forty independent living older adults (>65 years) without
      diagnosed cognitive impairment participated in either the intervention or control
      groups. INTERVENTION: A six week long progressively challenging EF focused CCT
      program was performed at home. MEASUREMENTS: Demographic variables, cognitive
      function (Trail-Making Test Part B) and GS were measured at baseline at week 7.
      Between group comparisons were completed for the whole sample initially with
      subgroup comparisons performed based on participants' initial GS (Slow walkers:
      GS<1.0m/s; Fast Walkers: GS>1.0m/s). RESULTS: No differences in GS were found for
      the whole population, but subgroup analyses restricted to slow walkers
      demonstrated a statistically significant improvement in GS after 6 weeks of CCT
      (u =0.33 m/s, p = 0.03). Other outcomes measures were not statistically different
      at posttest. CONCLUSIONS: Older adults who walk at speeds <1.0m/s may benefit
      from a progressively challenging CCT program when self-administered in the home.

PMID- 29205254
TI  - Primary Prevention of Dementia: An Epidemiological Point of View.
AB  - From an epidemiological perspective, in order to increase the level of evidence,
      it is necessary to refer to data from longitudinal studies to validate the
      temporal relationship between exposure (e.g. the behavior or modifying factor)
      and the disease. Findings from such studies are useful for defining risk factors
      and laying the groundwork for proposing interventions for prevention. This step
      is crucial in order to define the periods (life-course approach) and groups at
      risk, which will then become the targets of interventions designed to modify
      behaviors or lifestyle. Specifying the underlying mechanisms of these risk
      factors is one of the objectives of etiological epidemiology which focuses on the
      origin of diseases but is not essential for a more pragmatic interventional
      approach. These questions are essential for dementia prevention and are discussed
      in this paper. Furthermore, timing interventions is a major problem even if we
      identify primary prevention pathways in dementia. Another important concern for
      epidemiologists is the need to make projections to estimate the number of
      dementia cases in the next decades considering different intervention scenarios.
      These models require adequate descriptive indicators of dementia, demography and
      mortality and precise estimations of the impact of potential interventions in
      terms of delaying disease onset for instance.

PMID- 29205255
TI  - Combination Therapy of Anti-Tau and Anti-Amyloid Drugs for Disease Modification
      in Early-stage Alzheimer's Disease: Socio-economic Considerations Modeled on
      Treatments for Tuberculosis, HIV/AIDS and Breast Cancer.
AB  - Current drugs for treatment of mild to severe dementia of the Alzheimer's type
      include cholinesterase inhibitors and the NMDA non-competitive receptor
      antagonist memantine. There is controversy as to the additive benefit of these
      symptomatic drugs, and their effects are clinically modest. Patients with
      Alzheimer's disease (AD) are known to have characteristic pathology, including
      senile plaques with amyloid beta-protein aggregates and neurofibrillary tangles
      with assembled tau proteins, which start in the hippocampus and spread to
      neighboring areas. Amyloid and tau modifying drugs are under clinical testing.
      Based on this pathophysiology, it is crucial to investigate whether anti-amyloid
      and anti-tau combined therapy would show efficacy in early stage of AD, beyond
      what could be achieved with anti-amyloid or anti-tau monotherapy. It is equally
      important to consider the socio-economic implications of such a combination
      therapy, if effective. We hypothesize that the high costs of combination therapy
      for early-stage AD patients will require societal and public health initiatives
      to ensure universal access to AD treatment. In order to better predict these
      socio-economic implications, we summarize the management of other combination
      therapies used for tuberculosis, HIV/AIDS, and breast cancer, based on a database
      search of PubMed and other relevant sources. We put forward a framework for
      testing a potential anti-amyloid and anti-tau disease modifying combination
      therapy for early-stage AD patients and present an analysis of the socio-economic
      implications of such a combination therapy.

PMID- 29205256
TI  - The Case for Using Actigraphy Generated Sleep and Activity Endpoints in
      Alzheimer's Disease Clinical Trials.
AB  - More and more people in the industrialised world use wearables and smartphones to
      monitor their health and fitness. These devices are often used in combination
      with special apps to monitor and document daily activities and sleep. It would
      appear to be a logical step to assess the relevance of these devices in drug
      development trials. In contrast to the consumer devices, the technology used in
      clinical trials needs to be validated and compliant with the relevant
      regulations. Even under these complex requirements, wearables offer a number of
      new opportunities to objectively capture clinically relevant outcome measures 
      potentially with lower burden for patients and site staff. As an example, we
      describe the use in Alzheimer's disease drug development studies. This is an
      indication where there have been a number of failures, in part due to the
      difficulties this patient population has in reliably completing existing tools.
      In addition rater scales add complexity due to inter- and intra-rater
      variability.

PMID- 29205257
TI  - Ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin
      expression in adult mice.
AB  - Endothelial cells (ECs) are a key component of the blood-brain barrier (BBB).
      Healthy ECs in the BBB form inter-endothelial junctions, including adherens
      junctions (AJs). Under pathological conditions, such as after ischemic stroke,
      the BBB may be functionally compromised. However, gene and protein expression
      patterns involving endothelial AJs have not been well studied. Because expression
      levels of endothelial AJs are considered to be related to BBB functionality, we
      investigated the expression pattern of a representative endothelial AJ marker, VE
      cadherin, in healthy and diseased mice. We first examined the expression of VE
      cadherin in developing mouse brains. In addition, to a mouse model of cerebral
      infarction, we investigated the expression pattern of VE-cadherin in pathologic
      brains. Furthermore, using the Cre-LoxP system, we established a strain of mice
      expressing yellow fluorescent protein (YFP) under the control of the VE-cadherin
      promoter and investigated the expression pattern of YFP-expressing ECs in
      developing and pathologic murine brains. VE-cadherin protein and YFP expression
      driven by the VE-cadherin promoter both showed that VE-cadherin expression was
      weak during embryonic stages, followed by a steady increase postnatally, which
      then decreased during adulthood. However, following ischemic stroke,
      imunohistochemistry of VE-cadherin demonstrated an upregulation in ECs within
      ischemic regions, concomitant with YFP upregulation. These findings reveal that
      ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin
      protein expression, which suggests that endothelial VE-cadherin is involved in
      the reconstruction of the BBB following ischemic stroke.

PMID- 29205259
TI  - CD34+ selected stem cell boosts can improve poor graft function after paediatric
      allogeneic stem cell transplantation.
AB  - Poor graft function (PGF) is a severe complication of haematopoietic stem cell
      transplantation (HSCT) and administration of donor stem cell boosts (SCBs)
      represents a therapeutic option. We report 50 paediatric patients with PGF who
      received 61 boosts with CD34+ selected peripheral blood stem cells (PBSC) after
      transplantation from matched unrelated (n = 25) or mismatched related (n = 25)
      donors. Within 8 weeks, a significant increase in median neutrophil counts (0.6
      vs. 1.516 * 109 /l, P < 0.05) and a decrease in red blood cell and platelet
      transfusion requirement (median frequencies 1 and 7 vs. 0, P < 0.0001 and
      <0.001), were observed, and 78.8% of patients resolved one or two of their
      cytopenias. 36.5% had a complete haematological response. Median lymphocyte
      counts for CD3+ , CD3+ CD4+ , CD19+ and CD56+ increased 8.3-, 14.2-, 22.- and 1.6
      fold. The rate of de novo acute graft-versus-host disease (GvHD) grade I-III was
      only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred.
      Patients who responded to SCB displayed a trend toward better overall survival
      (OS) (P = 0.07). Thus, administration of CD34+ selected SCBs from alternative
      donors is safe and effective. Further studies are warranted to clarify the impact
      on immune reconstitution and survival.

PMID- 29205258
TI  - Sustained intra-cartilage delivery of low dose dexamethasone using a cationic
      carrier for treatment of post traumatic osteoarthritis.
AB  - Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue
      target sites at optimal doses for clinical efficacy. The dense, negatively
      charged matrix of cartilage poses a major hindrance to the transport of potential
      therapeutics. In this work, electrostatic interactions were utilised to overcome
      this challenge and enable higher uptake, full-thickness penetration and enhanced
      retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished
      by using the positively charged glycoprotein avidin as nanocarrier, conjugated to
      Dex by releasable linkers. Therapeutic effects of a single intra-articular
      injection of low dose avidin-Dex (0.5 mg Dex) were evaluated in rabbits 3 weeks
      after anterior cruciate ligament transection (ACLT). Immunostaining confirmed
      that avidin penetrated the full cartilage thickness and was retained for at least
      3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene
      expression to a greater extent than free Dex. It also significantly improved the
      histological score of cell infiltration and morphogenesis within the
      periarticular synovium. Micro-computed tomography confirmed the reduced incidence
      and volume of osteophytes following avidin-Dex treatment. However, neither
      treatment restored the loss of cartilage stiffness following ACLT, suggesting the
      need for a combinational therapy with a pro-anabolic factor for enhancing matrix
      biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG)
      loss, suggesting the use of higher Dex : avidin ratios in future formulations,
      such that the delivered avidin dose could be much less than that shown to affect
      GAGs. This charge-based delivery system converted cartilage into a drug depot
      that could also be employed for delivery to nearby synovium, menisci and
      ligaments, enabling clinical translation of a variety of DMOADs.

PMID- 29205260
TI  - Treatment of severe recalcitrant pyoderma gangrenosum with ustekinumab.
AB  - An increased expression of interleukin-23 has been observed in patients with
      pyoderma gangrenosum, leading to the use of ustekinumab as a therapeutic option.
      We report the successful use of ustekinumab in three patients with treatment
      resistant pyoderma gangrenosum of varying clinical presentations.

PMID- 29205262
TI  - Perceptions on the value of bodily functions in multiple sclerosis.
AB  - BACKGROUND: In neurological diseases presenting with a plethora of symptoms, the
      value of bodily functions for a given patient might be a guide for clinical
      management. Multiple sclerosis (MS) is paradigmatic in this respect, and little
      is known about the value of different bodily functions of patients and their
      physicians' perceptions. METHODS: In a multicenter study, 171 patients with
      relapsing-remitting multiple sclerosis (RRMS), 61% with a clinically active
      disease within the last 2 years were followed over up to 3 years and yearly
      patients and their study physician rated on the perceived value of 13 bodily
      functions via a priority list. Differences between patients and physicians as
      well as modulating disease demographic factors were analyzed. RESULTS: Patients
      with RRMS rated visual function followed by thinking and memory and walking
      highest while physicians stressed mobility, followed by thinking and memory and
      alertness most. Ratings were independent from disease duration or disability.
      Strongest value judgment differences were seen in swallowing regarded more
      relevant by patients and hand function regarded more relevant by physicians. In
      general, patients' and physicians' ratings through time were quite stable.
      Collapsing physical items into a physical functioning scale and mental items in a
      mental function scale, both dimensions were regarded equally important by
      patients while physicians underscored physical functioning (P = .016).
      CONCLUSION: There are differences between patients and physicians in value
      statements of bodily functions in MS. In particular, visual functioning is under
      recognized by physicians.

PMID- 29205263
TI  - LSD1 (KDM1A)-independent effects of the LSD1 inhibitor SP2509 in cancer cells.

PMID- 29205261
TI  - Report and Research Agenda of the American Geriatrics Society and National
      Institute on Aging Bedside-to-Bench Conference on Urinary Incontinence in Older
      Adults: A Translational Research Agenda for a Complex Geriatric Syndrome.
AB  - The American Geriatrics Society, with support from the National Institute on
      Aging and other funders, held its ninth Bedside-to-Bench research conference,
      entitled "Urinary Incontinence in the Older Adult: A Translational Research
      Agenda for a Complex Geriatric Syndrome," October 16 to 18, 2016, in Bethesda,
      Maryland. As part of a conference series addressing three common geriatric
      syndromes-delirium, sleep and circadian rhythm disturbance, and urinary
      incontinence-the series highlighted relationships and pertinent clinical and
      pathophysiological commonalities between these conditions. The conference
      provided a forum for discussing current epidemiology, basic science, and clinical
      and translational research on urinary incontinence in older adults; for
      identifying gaps in knowledge; and for developing a research agenda to inform
      future investigative efforts. The conference also promoted networking involving
      emerging researchers and thought leaders in the field of incontinence, aging, and
      other fields of research, as well as National Institutes of Health program
      personnel.

PMID- 29205265
TI  - The need for longer time horizons for cost-utility evaluation in bullous
      pemphigoid: reply from the authors.

PMID- 29205264
TI  - Diet, physical activity or both for prevention or delay of type 2 diabetes
      mellitus and its associated complications in people at increased risk of
      developing type 2 diabetes mellitus.
AB  - BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus
      (T2DM) could develop into a substantial health problem worldwide. Whether diet,
      physical activity or both can prevent or delay T2DM and its associated
      complications in at-risk people is unknown. OBJECTIVES: To assess the effects of
      diet, physical activity or both on the prevention or delay of T2DM and its
      associated complications in people at increased risk of developing T2DM. SEARCH
      METHODS: This is an update of the Cochrane Review published in 2008. We searched
      the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and
      reference lists of systematic reviews, articles and health technology assessment
      reports. The date of the last search of all databases was January 2017. We
      continuously used a MEDLINE email alert service to identify newly published
      studies using the same search strategy as described for MEDLINE up to September
      2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a
      duration of two years or more. DATA COLLECTION AND ANALYSIS: We used standard
      Cochrane methodology for data collection and analysis. We assessed the overall
      quality of the evidence using GRADE. MAIN RESULTS: We included 12 RCTs
      randomising 5238 people. One trial contributed 41% of all participants. The
      duration of the interventions varied from two to six years. We judged none of the
      included trials at low risk of bias for all 'Risk of bias' domains.Eleven trials
      compared diet plus physical activity with standard or no treatment. Nine RCTs
      included participants with impaired glucose tolerance (IGT), one RCT included
      participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT
      included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of
      12 deaths occurred in 2049 participants in the diet plus physical activity groups
      compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI
      0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials;
      very low-quality evidence). The definition of T2DM incidence varied among the
      included trials. Altogether 315 of 2122 diet plus physical activity participants
      (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%)
      (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511
      participants, 11 trials; moderate-quality evidence). Two trials reported serious
      adverse events. In one trial no adverse events occurred. In the other trial one
      of 51 diet plus physical activity participants compared with none of 51
      comparator participants experienced a serious adverse event (low-quality
      evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus
      physical activity participants and four of 1637 comparator participants (the RR
      ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low-quality
      evidence). Only one trial reported that no non-fatal myocardial infarction or non
      fatal stroke had occurred (low-quality evidence). Two trials reported that none
      of the participants had experienced hypoglycaemia. One trial investigated health
      related quality of life in 2144 participants and noted that a minimal important
      difference between intervention groups was not reached (very low-quality
      evidence). Three trials evaluated costs of the interventions in 2755
      participants. The largest trial of these reported an analysis of costs from the
      health system perspective and society perspective reflecting USD 31,500 and USD
      51,600 per quality-adjusted life year (QALY) with diet plus physical activity,
      respectively (low-quality evidence). There were no data on blindness or end-stage
      renal disease.One trial compared a diet-only intervention with a physical
      activity intervention or standard treatment. The participants had IGT. Three of
      130 participants in the diet group compared with none of the 141 participants in
      the physical activity group died (very low-quality evidence). None of the
      participants died because of cardiovascular disease (very low-quality evidence).
      Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical
      activity participants (41.1%) group developed T2DM (very low-quality evidence).
      No adverse events were recorded (very low-quality evidence). There were no data
      on non-fatal myocardial infarction, non-fatal stroke, blindness, end-stage renal
      disease, health-related quality of life or socioeconomic effects.Two trials
      compared physical activity with standard treatment in 397 participants. One trial
      included participants with IGT, the other trial included participants with IGT,
      IFG or both. One trial reported that none of the 141 physical activity
      participants compared with three of 133 control participants died. The other
      trial reported that three of 84 physical activity participants and one of 39
      control participants died (very low-quality evidence). In one trial T2DM
      developed in 58 of 141 physical activity participants (41.1%) compared with 90 of
      133 control participants (67.7%). In the other trial 10 of 84 physical activity
      participants (11.9%) compared with seven of 39 control participants (18%)
      developed T2DM (very low-quality evidence). Serious adverse events were rarely
      reported (one trial noted no events, one trial described events in three of 66
      physical activity participants compared with one of 39 control participants -
      very low-quality evidence). Only one trial reported on cardiovascular mortality
      (none of 274 participants died - very low-quality evidence). Non-fatal myocardial
      infarction or stroke were rarely observed in the one trial randomising 123
      participants (very low-quality evidence). One trial reported that none of the
      participants in the trial experienced hypoglycaemia. One trial investigating
      health-related quality of life in 123 participants showed no substantial
      differences between intervention groups (very low-quality evidence). There were
      no data on blindness or socioeconomic effects. AUTHORS' CONCLUSIONS: There is no
      firm evidence that diet alone or physical activity alone compared to standard
      treatment influences the risk of T2DM and especially its associated complications
      in people at increased risk of developing T2DM. However, diet plus physical
      activity reduces or delays the incidence of T2DM in people with IGT. Data are
      lacking for the effect of diet plus physical activity for people with
      intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did
      not investigate patient-important outcomes.

PMID- 29205266
TI  - Amphiphilic lysine conjugated to tobramycin synergizes legacy antibiotics against
      wild-type and multidrug-resistant Pseudomonas aeruginosa.
AB  - Peptidomimetic modification is a common route of optimization for biologically
      active peptides. Previous studies in our group have shown that conjugation of
      amphiphilic tobramycin to other antibacterials enhance their latent outer
      membrane permeabilizing and efflux blocking activity toward Gram-negative
      pathogens including Pseudomonas aeruginosa. Herein, we describe the antimicrobial
      adjuvant properties of amphiphilic lysine ligated to tobramycin. The most potent
      amphiphilic lysine-tobramycin conjugate 3 potentiated the antibacterial efficacy
      of 8 clinically used antibiotics against wild type, multidrug- and extensively
      drug-resistant P. aeruginosa isolates from Canadian hospitals whereas amphiphilic
      lysine 4 did not. Antibiotics that are synergistic with conjugate 3 included
      moxifloxacin, ciprofloxacin, erythromycin, chloramphenicol, trimethoprim,
      novobiocin, linezolid, and fosfomycin. Out of these 8 antibiotics, novobiocin
      showed highest synergy.

PMID- 29205267
TI  - The absolute percent deviation of IGHV mutation rather than a 98% cut-off
      predicts survival of chronic lymphocytic leukaemia patients treated with
      fludarabine, cyclophosphamide and rituximab.

PMID- 29205268
TI  - Hidradenitis and smoking.

PMID- 29205269
TI  - Imatinib-related interstitial lung disease.

PMID- 29205270
TI  - Severe multiple sclerosis reactivation during prolonged lymphopenia after
      dimethyl fumarate discontinuation.
AB  - BACKGROUND: Delayed-release dimethyl fumarate (DMF) treatment can be associated
      with reduced lymphocyte and leucocyte counts, which might persist after DMF
      discontinuation. CASE PRESENTATION: We report the case of a patient with severe
      disease reactivation despite prolonged lymphopenia after DMF discontinuation. We
      describe the frequency and impact of prolonged lymphopenia after DMF
      discontinuation at two tertiary MS centres. A 36-year-old female patient with
      multiple sclerosis was switched to DMF after 14 years of treatment with
      interferon beta-1a. DMF was suspended after 4 months because of persistent
      lymphopenia for 3 months. Six months later, the patient had a severe relapse with
      multiple enhancing brain lesions at MRI although lymphopenia was still
      persistent. Haematological assessment excluded other causes of lymphopenia, which
      was evaluated as a probable iatrogenic complication of DMF. The patient was
      treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical
      recovery. CONCLUSIONS: Prolonged lymphopenia after DMT discontinuation does not
      protect against disease reactivation. Starting a new immune therapy should be
      balanced against the option of a "wait and see." A different immunotherapeutic
      strategy such as an anti-B therapeutic approach could be considered.

PMID- 29205271
TI  - A randomized controlled trial of the ketogenic diet in refractory childhood
      epilepsy.

PMID- 29205272
TI  - Complex relations between body temperature, tPA action, and stroke outcome.

PMID- 29205273
TI  - A randomized controlled trial of the ketogenic diet in refractory childhood
      epilepsy.

PMID- 29205274
TI  - Production of cellulosic organic acids via synthetic fungal consortia.
AB  - Consolidated bioprocessing (CBP) is a potential breakthrough technology for
      reducing costs of biochemical production from lignocellulosic biomass. Production
      of cellulase enzymes, saccharification of lignocellulose, and conversion of the
      resulting sugars into a chemical of interest occur simultaneously within a single
      bioreactor. In this study, synthetic fungal consortia composed of the
      cellulolytic fungus Trichoderma reesei and the production specialist Rhizopus
      delemar demonstrated conversion of microcrystalline cellulose (MCC) and alkaline
      pre-treated corn stover (CS) to fumaric acid in a fully consolidated manner
      without addition of cellulase enzymes or expensive supplements such as yeast
      extract. A titer of 6.87 g/L of fumaric acid, representing 0.17 w/w yield, were
      produced from 40 g/L MCC with a productivity of 31.8 mg/L/hr. In addition, lactic
      acid was produced from MCC using a fungal consortium with Rhizopus oryzae as the
      production specialist. These results are proof-of-concept demonstration of
      engineering synthetic microbial consortia for CBP production of naturally
      occurring biomolecules.

PMID- 29205275
TI  - Antenatal maternal education for improving postnatal perineal healing for women
      who have birthed in a hospital setting.
AB  - BACKGROUND: The female perineum becomes suffused and stretched during pregnancy,
      and further strain during vaginal childbirth contributes to approximately 85% of
      women experiencing some degree of trauma to the perineal region. Multiple factors
      play a role in the type and severity of trauma experienced, including parity,
      delivery method, and local practices. There is ongoing debate about best
      midwifery practice to reduce perineal trauma. Once perineal trauma has occurred,
      treatment also varies greatly, depending on its degree and severity, local
      practice and customs, and personal preference. In order to optimise wound-healing
      outcomes, it is important that wounds are assessed and managed in an appropriate
      and timely manner. A perineal wound may cause significant physical and/or
      psychological impact in the short or long term, however little evidence is
      available on this subject.Antenatal education serves to prepare women and their
      partners for pregnancy, delivery and the postpartum period. The delivery of this
      education varies widely in type, content, and nature. This review examined
      antenatal education which is specifically tailored towards perineal care and
      wound healing in the postnatal period via formal channels. Appropriate patient
      education positively impacts on wound-healing rates and compliance with wound
      care. Risk factors that contribute to the breakdown of wounds and poor healing
      rates may be addressed antenatally in order to optimise postnatal wound healing.
      It is important to assess whether or not antenatal wound-care education
      positively affects perineal healing, in order to empower women to incorporate
      best practice, evidence-based treatment with this important aspect of self-care
      in the immediate postnatal period. OBJECTIVES: To evaluate the effects of
      antenatal education on perineal wound healing in postnatal women who have birthed
      in a hospital setting, and who have experienced a break in the skin of the
      perineum as a result of a tear or episiotomy, or both. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30
      September 2017), ClinicalTrials.gov (8th September 2017), the WHO International
      Clinical Trials Registry Platform (ICTRP) (8th September 2017) and reference
      lists of retrieved studies. SELECTION CRITERIA: We considered randomised
      controlled trials (RCTs) which referred to all formal methods of antenatal
      education and addressed care of a potential perineal wound as a result of a tear
      or episiotomy, which was experienced by pregnant women who planned to give birth
      within a hospital setting.Trials using a cluster-RCT and a quasi-randomised
      design would have been eligible for inclusion in this review but none were
      identified. Cross-over trials were not eligible for inclusion in this review.
      Studies published in abstract form would have been eligible for inclusion in this
      review, but none were identified.We planned to consider all formal methods of
      antenatal education which addressed care of a perineal wound. We also planned to
      consider all contact points where there was an opportunity for formal education,
      including midwifery appointments, antenatal education classes, obstetrician
      appointments, general practitioner appointments and physiotherapist appointments.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles
      and abstracts of the studies identified by the search strategy for their
      eligibility. MAIN RESULTS: No studies met the inclusion criteria for this review.
      We excluded one study and one other study is ongoing. AUTHORS' CONCLUSIONS: We
      set out to evaluate the RCT evidence pertaining to the impact of antenatal
      education on perineal wound healing in postnatal women who have birthed in a
      hospital setting, and who experienced a break in the skin of the perineum as a
      result of a tear or episiotomy, or both. However, no studies met the inclusion
      criteria. There is a lack of evidence concerning whether or not antenatal
      education relating to perineal wound healing in this cohort of women will change
      the outcome for these women in relation to wound healing, infection rate, re
      attendance or re-admission to hospital, pain, health-related quality of life,
      maternal bonding, and negative emotional experiences. Further study is warranted
      in this area given the significant physical, psychological and economic impact of
      perineal wounds, and the large proportion of childbearing women who have
      experienced a postnatal wound. The benefits of any future research in this field
      would be maximised by incorporating women in a range of socio-economic groups,
      and with a range of healthcare options. This research could take both a
      qualitative and a quantitative approach and examine the outcomes identified in
      this review in order to assess fully the potential benefits of a tailored
      antenatal package, and to make recommendations for future practice. There is
      currently no evidence to inform practice in this regard.

PMID- 29205276
TI  - Response to 'Phase IV head-to-head randomized controlled trial comparing ingenol
      mebutate 0.015% gel with diclofenac sodium 3% gel for the treatment of actinic
      keratosis on the face or scalp'.

PMID- 29205278
TI  - Jack Aviv and brains of children.
AB  - Both lead intoxication in early childhood and deficient bilirubin-binding
      capacity (BBC) of blood in jaundiced neonates indicate risk for brain damage.
      Zinc protoporphyrin (ZPP) is a biomarker for lead intoxication (PbI) as well as
      well as for iron deficiency. Under the leadership of Jack Aviv, Aviv Biomedical,
      Inc. developed robust hematofluorometers for point-of-care assays of ZPP in blood
      and for the high-affinity BBC of blood. These assays use just drops of whole
      blood and are simple, fast and inexpensive. ZPP by hematofluorometry has been
      used world-wide as a primary screen for lead intoxication since 1979. Recent
      clinical studies enabled by an Aviv Biomedical, Inc. bilirubin hematofluorometer
      have renewed interest in BBC-based assessment of neurotoxicity for improved
      management of neonatal jaundice. This article sketches Jack Aviv's contribution
      to the development and application of hematofluorometry.

PMID- 29205277
TI  - Clinical and genetic factors are associated with pain and hospitalisation rates
      in sickle cell anaemia in Cameroon.
AB  - We aimed to investigate the clinical and genetic predictors of painful vaso
      occlusive crises (VOC) in sickle cell disease (SCD) in Cameroon. Socio
      demographics, clinical variables/events and haematological indices were acquired.
      Genotyping was performed for 40 variants in 17 pain-related genes, three fetal
      haemoglobin (HbF)-promoting loci, two kidney dysfunctions-related genes, and
      HBA1/HBA2 genes. Statistical models using regression frameworks were performed in
      R(r) . A total of 436 hydoxycarbamide- and opioid-naive patients were studied;
      median age was 16 years. Female sex, body mass index, Hb/HbF, blood transfusions,
      leucocytosis and consultation or hospitalisation rates significantly correlated
      with VOC. Three pain-related genes variants correlated with VOC (CACNA2D3
      rs6777055, P = 0.025; DRD2-rs4274224, P = 0.037; KCNS1-rs734784, P = 0.01). Five
      pain-related genes variants correlated with hospitalisation/consultation rates.
      (COMT-rs6269, P = 0.027; FAAH-rs4141964, P = 0.003; OPRM1-rs1799971, P = 0.031;
      ADRB2-rs1042713; P < 0.001; UGT2B7-rs7438135, P = 0.037). The 3.7 kb HBA1/HBA2
      deletion correlated with increased VOC (P = 0.002). HbF-promoting loci variants
      correlated with decreased hospitalisation (BCL11A-rs4671393, P = 0.026; HBS1L-MYB
      rs28384513, P = 0.01). APOL1 G1/G2 correlated with increased hospitalisation (P =
      0.048). This first study from Africa has provided evidence supporting possible
      development of genetic risk model for pain in SCD.

PMID- 29205279
TI  - Paramagnetism in Bacillus spores: Opportunities for novel biotechnological
      applications.
AB  - Spores of Bacillus megaterium, Bacillus cereus, and Bacillus subtilis were found
      to exhibit intrinsic paramagnetic properties as a result of the accumulation of
      manganese ions. All three Bacillus species displayed strong yet distinctive
      magnetic properties arising from differences in manganese quantity and valency.
      Manganese ions were found to accumulate both within the spore core as well as
      being associated with the surface of the spore. Bacillus megaterium spores
      accumulated up to 1 wt.% manganese (II) within, with a further 0.6 wt.% adsorbed
      onto the surface. At room temperature, Bacillus spores possess average magnetic
      susceptibilities in the range of 10-6 to 10-5 . Three spore-related
      biotechnological applications-magnetic sensing, magnetic separation and metal ion
      adsorption-were assessed subsequently, with the latter two considered as having
      the most potential for development.

PMID- 29205281
TI  - The need for longer time horizons for cost-utility evaluation in bullous
      pemphigoid.

PMID- 29205280
TI  - Maximizing neotissue growth kinetics in a perfusion bioreactor: An in silico
      strategy using model reduction and Bayesian optimization.
AB  - In regenerative medicine, computer models describing bioreactor processes can
      assist in designing optimal process conditions leading to robust and economically
      viable products. In this study, we started from a (3D) mechanistic model
      describing the growth of neotissue, comprised of cells, and extracellular matrix,
      in a perfusion bioreactor set-up influenced by the scaffold geometry, flow
      induced shear stress, and a number of metabolic factors. Subsequently, we applied
      model reduction by reformulating the problem from a set of partial differential
      equations into a set of ordinary differential equations. Comparing the reduced
      model results to the mechanistic model results and to dedicated experimental
      results assesses the reduction step quality. The obtained homogenized model is
      105 fold faster than the 3D version, allowing the application of rigorous
      optimization techniques. Bayesian optimization was applied to find the medium
      refreshment regime in terms of frequency and percentage of medium replaced that
      would maximize neotissue growth kinetics during 21 days of culture. The
      simulation results indicated that maximum neotissue growth will occur for a high
      frequency and medium replacement percentage, a finding that is corroborated by
      reports in the literature. This study demonstrates an in silico strategy for
      bioprocess optimization paying particular attention to the reduction of the
      associated computational cost.

PMID- 29205282
TI  - Instructor personality matters for student evaluations: Evidence from two subject
      areas at university.
AB  - BACKGROUND: Instructors are under pressure to produce excellent outcomes in
      students. Although the contribution of student personality on student outcomes is
      well established, the contribution of instructor personality to student outcomes
      is largely unknown. AIM: This study examined the influence of instructor
      personality (as reported by both students and instructors themselves) on student
      educational outcomes at university. SAMPLE AND METHOD: Mathematics and psychology
      university students (N = 515) and their instructors (n = 45) reported their
      personality under the Big Five framework. RESULTS: Multilevel regressions were
      conducted to predict each outcome from instructor personality, taking into
      account the effects of student gender, age, cognitive ability, and personality,
      as well as instructor gender and age. Student-reports of instructor personality
      predicted student evaluations of teaching but not performance self-efficacy or
      academic achievement. Instructor self-reports did not predict any of the
      outcomes. Stronger associations between student-reports and the outcomes than
      instructor self-reports could be explained by students providing information on
      both the predictor and the outcome variables, as well as a greater number of
      raters providing information on instructor personality. Different domains of the
      instructor Big Five were important for different element of student evaluations
      of teaching. CONCLUSIONS: The study highlights the importance of studying
      instructor personality, especially through other-reports, to understand students'
      educational experiences. This has implications for how tertiary institutions
      should use and interpret student evaluations.

PMID- 29205283
TI  - Clinician factors associated with prescribing nicotine replacement therapy in
      pregnancy: A cross-sectional survey of Australian obstetricians and general
      practitioners.
AB  - The use of nicotine replacement therapy in pregnancy has been debated but
      evidence suggests that it is safer than smoking. A cross-sectional survey was
      conducted with: (i) general practitioners and obstetricians from a college
      database; and (ii) general practitioners with a special interest in Indigenous
      health. General practitioners had higher odds of prescribing compared to
      obstetricians. Reading guidelines, confidence, viewing nicotine replacement
      therapy as safe, effective and with good adherence, also significantly increased
      the odds of prescription. Clear guidance regarding safety and efficacy, with
      practical clinical protocols, are required in order to reduce variation in
      prescribing rates across these clinicians.

PMID- 29205284
TI  - Magnitude of benefit for topical crisaborole in the treatment of atopic
      dermatitis in children and adults does not look promising: a critical appraisal.
AB  - AIM: To assess the efficacy and safety of crisaborole ointment, a
      phosphodiesterase 4 inhibitor, for the treatment of mild or moderate atopic
      dermatitis (AD) in two phase III studies (AD-301 and AD-302). DESIGN AND SETTING:
      Two identically designed multicentre, double-blind randomized controlled trials
      were conducted in the U.S.A. Participants were randomized 2 : 1 to receive
      crisaborole or vehicle treatment. In total 47 and 42 investigational centres were
      identified for AD-301 and AD-302, respectively. STUDY PARTICIPANTS: Inclusion
      criteria were identified as age >= 2 years, clinical diagnosis of AD (as per the
      Hanifin and Rajka criteria), >= 5% body surface area involvement, and baseline
      Investigator's Static Global Assessment (ISGA) mild or moderate. Exclusion
      criteria included previous use of biologics or systemic corticosteroids (within
      the last 28 days) or a topical calcineurin inhibitor/corticosteroid (within the
      last 14 days), and active skin infection. EXPOSURES: Participants were instructed
      to apply the study drug twice daily to all lesions identified at baseline, and
      all new lesions identified after day 1 (with weekly review of application
      instructions). Bland emollients were permitted to be used on skin not treated
      with the study drug. PRIMARY OUTCOME: The primary outcome was defined as ISGA
      clear or almost clear at day 29, with a 2-grade or more improvement from
      baseline. OUTCOMES: Secondary outcomes included the proportion of patients with
      an ISGA score of clear or almost clear at day 29, and time to success in ISGA
      score. Additional outcomes included pruritus severity and signs of AD (erythema,
      exudation, excoriation, induration/papulation and lichenification), and were
      measured on a 4-point scale (none, mild, moderate, severe). Adverse events were
      also recorded. RESULTS: More participants in the crisaborole-treated group
      achieved ISGA scores of clear or almost clear with >= 2-grade improvement than in
      the vehicle-treated group (AD-301, 32.8% vs. 25.4%, P = 0.38; AD-302, 31.4% vs.
      18.0%, P < 0.001). Greater percentages of clear and almost clear scores were
      observed in the treatment groups (51.7% vs. 40.6%, P = 0.005; 48.5% vs. 29.7%; P
      < 0.001), as well as earlier success in ISGA score and improvement in pruritus (P
      <= 0.001). No serious treatment-related adverse events were identified.
      CONCLUSIONS: Based on the study results, the authors suggest that crisaborole is
      a safe treatment that improves disease severity, pruritus and clinical signs
      associated with AD.

PMID- 29205285
TI  - Vitamin B12 association with mAbs: Mechanism and potential mitigation strategies.
AB  - Process control for manufacturing biologics is critical for ensuring product
      quality, safety, and lot to lot consistency of therapeutic proteins. In this
      study, we investigated the root cause of the pink coloration observed for various
      in-process pools and drug substances in the antibody manufacturing process.
      Vitamin B12 is covalently bound to mAbs via a cobalt-sulfur coordinate bond via
      the cysteine residues. The vitamin B12 was identified to attach to an IgG4
      molecule at cysteine residues on light chain (Cys-214), and heavy chain (Cys-134,
      Cys-321, Cys-367, and Cys-425). Prior to attachment to mAbs, the vitamin B12
      needs to be in its active form of hydroxocobalamin. During culture media
      preparation, storage and cell culture processing, cyanocobalamin, the chemical
      form of vitamin B12 added to media, is converted to hydroxocobalamin by white
      fluorescence light (about 50% degradation in 11-14 days at room temperature and
      with room light intensity about 500-1,000 lux) and by short-wavelength visible
      light (400-550 nm). However, cyanocobalamin is stable under red light (wavelength
      >600 nm) exposure and does not convert to hydroxocobalamin. Our findings suggests
      that the intensity of pink color depends on concentrations of both free
      sulfhydryl groups on reduced mAb and hydroxocobalamin, the active form of vitamin
      B12 . Both reactants are necessary and neither one of them is sufficient to
      generate pink color, therefore process control strategy can consider limiting
      either one or both factors. A process control strategy to install red light
      (wavelength >600 nm) in culture media preparation, storage and culture processing
      areas is proposed to provide safe light for biologics and to prevent light
      induced color variations in final products.

PMID- 29205286
TI  - Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung
      cancer and cachexia: Results from a randomized, double-blind, placebo-controlled,
      multicenter study of Japanese patients (ONO-7643-04).
AB  - BACKGROUND: Cachexia, described as weight loss (mainly in lean body mass [LBM])
      and anorexia, is common in patients with advanced cancer. This study examined the
      efficacy and safety of anamorelin (ONO-7643), a novel selective ghrelin receptor
      agonist, in Japanese cancer patients with cachexia. METHODS: This double-blind
      clinical trial (ONO-7643-04) enrolled 174 patients with unresectable stage III/IV
      non-small cell lung cancer (NSCLC) and cachexia in Japan. Patients were
      randomized to daily oral anamorelin (100 mg) or a placebo for 12 weeks. The
      primary endpoint was the change from the baseline LBM (measured with dual-energy
      x-ray absorptiometry) over 12 weeks. The secondary endpoints were changes in
      appetite, body weight, quality of life, handgrip strength (HGS), and 6-minute
      walk test (6MWT) results. RESULTS: The least squares mean change (plus or minus
      the standard error) in LBM from the baseline over 12 weeks was 1.38 +/- 0.18 and 
      0.17 +/- 0.17 kg in the anamorelin and placebo groups, respectively (P < .0001).
      Changes from the baseline in LBM, body weight, and anorexia symptoms showed
      significant differences between the 2 treatment groups at all time points.
      Anamorelin increased prealbumin at weeks 3 and 9. No changes in HGS or 6MWT were
      detected between the groups. Twelve weeks' treatment with anamorelin was safe and
      well tolerated in NSCLC patients. CONCLUSIONS: Anamorelin significantly increased
      LBM and improved anorexia symptoms and the nutritional state, but not motor
      function, in Japanese patients with advanced NSCLC. Because no effective
      treatment for cancer cachexia is currently available, anamorelin can be a
      beneficial treatment option. Cancer 2018;124:606-16. (c) 2017 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- 29205287
TI  - Is less more? Comparing chemotherapy alone with chemotherapy and radiation for
      high-risk grade 2 glioma: An analysis of the National Cancer Data Base.
AB  - BACKGROUND: The addition of chemotherapy to adjuvant radiotherapy (chemotherapy
      and radiation therapy [CRT]) improves overall survival (OS) for patients with
      high-risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is
      unknown. This study compares the OS of patients with high-risk grade 2 gliomas
      treated with CA versus CRT. METHODS: Patients with high-risk grade 2 gliomas
      (subtotal resection or age >= 40 years) with oligodendrogliomas, astrocytomas, or
      mixed tumors were identified with the National Cancer Data Base. Patients were
      grouped into CA and CRT cohorts. Univariate analyses and multivariate analyses
      (MVAs) were performed. Propensity score (PS) matching was also implemented. The
      Kaplan-Meier method was used to analyze OS. RESULTS: A total of 1054 patients
      with high-risk grade 2 gliomas were identified: 496 (47.1%) received CA, and 558
      (52.9%) received CRT. Patients treated with CA were more likely (all P values <
      .05) to have oligodendroglioma histology (65.5% vs 34.2%), exhibit a 1p/19q
      codeletion (22.8% vs 7.5%), be younger (median age, 47.0 vs 48.0 years), and
      receive treatment at an academic facility (65.2% vs 50.3%). The treatment type
      was not a significant predictor for OS (P = .125) according to the MVA; a tumor
      size > 6 cm, astrocytoma histology, and older age were predictors for worse OS
      (all P values < .05). After 1:1 PS matching (n = 331 for each cohort), no OS
      difference was seen (P = .696) between the CA and CRT cohorts at 5 (69.3% vs
      67.4%) and 8 years (52.8% vs 56.7%). CONCLUSIONS: No long-term OS difference was
      seen in patients with high-risk grade 2 gliomas treated with CA versus CRT. These
      findings are hypothesis-generating, and prospective clinical trials comparing
      these treatment paradigms are warranted. Cancer 2018;124:1169-78. (c) 2017
      American Cancer Society.

PMID- 29205288
TI  - Phosphorus limitation of aboveground production in northern hardwood forests.
AB  - Forest productivity on glacially derived soils with weatherable phosphorus (P) is
      expected to be limited by nitrogen (N), according to theories of long-term
      ecosystem development. However, recent studies and model simulations based on
      resource optimization theory indicate that productivity can be co-limited by N
      and P. We conducted a full factorial N * P fertilization experiment in 13
      northern hardwood forest stands of three age classes in central New Hampshire,
      USA, to test the hypothesis that forest productivity is co-limited by N and P. We
      also asked whether the response of productivity to N and P addition differs among
      species and whether differential species responses contribute to community-level
      co-limitation. Plots in each stand were fertilized with 30 kg N.ha-1 .yr-1 , 10
      kg P.ha-1 .yr-1 , N + P, or neither nutrient (control) for four growing seasons.
      The productivity response to treatments was assessed using per-tree annual
      relative basal area increment (RBAI) as an index of growth. RBAI responded
      significantly to P (P = 0.02) but not to N (P = 0.73). However, evidence for P
      limitation was not uniform among stands. RBAI responded to P fertilization in mid
      age (P = 0.02) and mature (P = 0.07) stands, each taken as a group, but was
      greatest in N-fertilized plots of two stands in these age classes, and there was
      no significant effect of P in the young stands. Both white birch (Betula
      papyrifera Marsh.) and beech (Fagus grandifolia Ehrh.) responded significantly to
      P; no species responded significantly to N. We did not find evidence for N and P
      co-limitation of tree growth. The response to N + P did not differ from that to P
      alone, and there was no significant N * P interaction (P = 0.68). Our P
      limitation results support neither the N limitation prediction of ecosystem
      theory nor the N and P co-limitation prediction of resource optimization theory,
      but could be a consequence of long-term anthropogenic N deposition in these
      forests. Inconsistencies in response to P suggest that successional status and
      variation in site conditions influence patterns of nutrient limitation and
      recycling across the northern hardwood forest landscape.

PMID- 29205289
TI  - Can mesophotic reefs replenish shallow reefs? Reduced coral reproductive
      performance casts a doubt.
AB  - Mesophotic coral ecosystems (i.e., deep coral reefs at 30-120 m depth) appear to
      be thriving while many shallow reefs in the world are declining. Amid efforts to
      understand and manage their decline, it was suggested that mesophotic reefs might
      serve as natural refuges and a possible source of propagules for the shallow
      reefs. However, our knowledge of how reproductive performance of corals alters
      with depth is sparse. Here, we present a comprehensive study of the reproductive
      phenology, fecundity, and abundance of seven reef-building conspecific corals in
      shallow and mesophotic habitats. Significant differences were found in the
      synchrony and timing of gametogenesis and spawning between shallow and mesophotic
      coral populations. Thus, mesophotic populations exhibited delayed or protracted
      spawning events, which led to spawning of the mesophotic colonies in large
      proportions at times where the shallow ones had long been depleted of
      reproductive material. All species investigated demonstrated a substantial
      reduction in fecundity and/or oocyte sizes at mesophotic depths (40-60 m). Two
      species (Seriatopora hystrix and Galaxea fascicularis) displayed a reduction in
      both fecundity and oocyte size at mesophotic depths. Turbinaria reniformis had
      only reduced fecundity and Acropora squarrosa and Acropora valida only reduced
      oocyte size. In Montipora verrucosa, reduced fecundity was found during one
      annual reproductive season while, in the following year, only reduced oocyte size
      was found. In contrast, reduced oocyte size in mesophotic populations of Acropora
      squarrosa was consistent along three studied years. One species, Acropora
      pharaonis, was found to be infertile at mesophotic depths along two studied
      years. This indicates that reproductive performance decreases with depth; and
      that although some species are capable of reproducing at mesophotic depths, their
      contribution to the replenishment of shallow reefs may be inconsequential.
      Reduced reproductive performance with depth, combined with the possible narrower
      tolerance to environmental factors, further suggests that mesophotic corals may
      in fact be more vulnerable than previously conceived. Furthermore, we posit that
      the observed temporal segregation in reproduction could lead to assortative
      mating, and this, in turn, may facilitate adaptive divergence across depth.

PMID- 29205290
TI  - Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic
      leukemia: A report from the St. Jude Lifetime Cohort study.
AB  - BACKGROUND: Sedentary behaviors are associated with poor health outcomes in the
      general population, but their clinical impact on adult survivors of childhood
      acute lymphoblastic leukemia (ALL) has not been characterized to date. In the
      current study, we described the prevalence of sedentary behaviors in survivors of
      ALL and examined associations between time spent sedentary and body composition
      and onset of cardiovascular disease (CVD) risk factors. METHODS: Participants'
      self-reported screen time (eg, television, computer) and activity as measured by
      accelerometer were used to determine activity time (sedentary, light activity,
      and moderate or vigorous physical activity). The percentage of time spent in each
      activity was compared between 331 survivors of ALL and 330 controls. Associations
      between time sedentary and body composition were evaluated in survivors using
      linear regression models. Cox proportional hazard models were used to examine the
      association between time sedentary at baseline and CVD risk factor onset during
      follow-up. RESULTS: Survivors spent approximately 65% of their time sedentary,
      32% in light activity, and 2% in moderate or vigorous physical activity compared
      with 67% (P = .04), 30% (P<.01), and 3% (P<.01), respectively, in controls. Among
      survivors, percentage lean body mass decreased by 1.0% +/- 0.4% (P = .01) per 10%
      increase in time sedentary. Survivors who were sedentary >=60% per day were found
      to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95%
      confidence interval, 1.12-5.64) and any CVD risk factor (hazard ratio, 1.96; 95%
      confidence interval, 1.16-3.30). CONCLUSIONS: Sedentary behavior is associated
      with low lean mass and CVD risk factor development and should be limited in
      survivors of childhood ALL. Cancer 2018;124:1036-43. (c) 2017 American Cancer
      Society.

PMID- 29205291
TI  - Interactive effects of seizure frequency and lateralization on intratemporal
      effective connectivity in temporal lobe epilepsy.
AB  - OBJECTIVE: Patients with temporal lobe epilepsy (TLE) show brain connectivity
      changes in association with cognitive impairment. Seizure frequency and
      lateralization are 2 important clinical factors that characterize epileptic
      seizures. In this study, we sought to examine an interactive effect of the 2
      seizure factors on intratemporal effective connectivity based on resting-state
      functional magnetic resonance imaging (rsfMRI) in patients with TLE. METHODS: For
      rsfMRI data acquired from 48 TLE patients and 45 healthy controls, we applied
      stochastic dynamical causal modeling to infer effective connectivity between 3
      medial temporal lobe (MTL) regions, including the hippocampus (Hipp),
      parahippocampal gyrus (PHG), and amygdala (Amyg), ipsilateral to the seizure
      focus. We searched for the effect of the 2 seizure factors, seizure frequency
      (good vs poor seizure control) and lateralization (left vs right TLE), on
      connection strengths and their relationship with the level of verbal memory and
      language impairment. RESULTS: Impairment of verbal memory and language function
      was mainly affected by seizure lateralization, consistent with preferential
      involvement of the left MTL in verbal mnemonic processing. For the fully
      connected model, which was selected as the effective connectivity structure that
      best explained the observed rsfMRI time series, alterations in connection
      strengths were primarily influenced by seizure frequency; there was an increase
      in the strength of the Hipp to PHG connection in TLE patients with poor seizure
      control, whereas the strength of the Amyg to PHG connection increased in those
      with good seizure control. Furthermore, the association between connection
      strength alterations and cognitive impairment was interactively affected by both
      seizure frequency and lateralization. SIGNIFICANCE: These findings suggest an
      interactive effect as well as an individual effect of seizure frequency and
      lateralization on neuroimaging features and cognitive function. This potential
      interaction needs to be evaluated in the consideration of multiple seizure
      factors.

PMID- 29205293
TI  - Cancer cachexia: Are we ready to take a step forward?

PMID- 29205292
TI  - Brain regions and epileptogenicity influence epileptic interictal spike
      production and propagation during NREM sleep in comparison with wakefulness.
AB  - OBJECTIVE: Non-rapid eye movement (NREM) sleep is known to be a brain state
      associated with an activation of interictal epileptic activity. The goal of this
      work was to quantify topographic changes occurring during NREM sleep in
      comparison with wakefulness. METHOD: We studied intracerebral recordings of 20
      patients who underwent stereo-electroencephalography (SEEG) during presurgical
      evaluation for pharmacoresistant focal epilepsy. We measured the number of
      interictal spikes (IS) and quantified the co-occurrence of IS between brain
      regions during 1 hour of NREM sleep and 1 hour of wakefulness. Co-occurrence is a
      method to estimate IS networks based on a temporal concordance between IS of
      different brain regions. Each studied region was labeled as "seizure-onset zone"
      (SOZ), "propagation zone" (PZ), or "not involved region" (NIR). RESULTS: During
      NREM sleep, the number of interictal spikes significantly increased in all
      regions (mean of 68%). This increase was higher in medial temporal regions than
      in other regions, whether involved in the SOZ. Spike co-occurrence increased
      significantly in all regions during NREM sleep in comparison with wakefulness but
      was greater in neocortical regions. Spike co-occurrence in medial temporal
      regions was not higher than in other regions, suggesting that the increase of the
      number of spikes in this region was in great part a local effect. SIGNIFICANCE:
      This study demonstrated that medial temporal regions show a greater propensity to
      spike production or propagation during NREM sleep compared to other brain
      regions, even when the medial temporal lobe is not involved in the SOZ.

PMID- 29205294
TI  - Wearable Devices in Clinical Trials: Hype and Hypothesis.
AB  - The development of innovative wearable technologies has raised great interest in
      new means of data collection in healthcare and biopharmaceutical research and
      development. Multiple applications for wearables have been identified in a number
      of therapeutic areas; however, researchers face many challenges in the clinic,
      including scientific methodology as well as regulatory, legal, and operational
      hurdles. To facilitate further evaluation and adoption of these technologies, we
      highlight methodological and logistical considerations for implementation in
      clinical trials, including key elements of analytical and clinical validation in
      the specific context of use (COU). Additionally, we provide an assessment of the
      maturity of the field and successful examples of recent clinical experiments.

PMID- 29205295
TI  - Protein Abundance of Clinically Relevant Drug-Metabolizing Enzymes in the Human
      Liver and Intestine: A Comparative Analysis in Paired Tissue Specimens.
AB  - This work revises and complements existing findings on the distribution of drug
      metabolizing enzymes in the first-pass effect organs. We explored gene expression
      (quantitative polymerase chain reaction) and protein abundance (liquid
      chromatography/ tandem mass spectrometry) of CYP1A2, CYP2B6, CYP2C8/9/19, CYP2D6,
      CYP2E1, CYP3A4/5, UGT1A1/3, UGT2B7/15 in the liver, duodenum, jejunum, ileum, and
      colon in paired tissues from nine organ donors. All proteins were detected in the
      liver, but in the intestine CYP2C9/19, CYP2D6, CYP3A4/5, UGT1A1/3, and UGT2B7
      were found. CYP3A4 showed comparable abundance in the liver and jejunum, whereas
      other enzymes were markedly higher in the hepatic tissue. Nearly all detected
      enzymes showed their highest abundance in the jejunum. Significant correlations
      between mRNA and protein levels in liver or intestine were found for most
      enzymes. CYP3A4 and CYP3A5 protein abundance, but not other enzymes, were
      significantly correlated in the liver and the small intestine. Our data may
      contribute to an improved understanding of hepatic and intestinal drug
      metabolism.

PMID- 29205296
TI  - Impact of latency time on survival for adolescents and young adults with a second
      primary malignancy.
AB  - BACKGROUND: The adverse impact of second primary malignancies (SPMs) on survival
      is substantial for adolescents and young adults (AYAs; ie, those 15-39 years
      old). No studies have evaluated whether the latency time between the first
      malignancy (the primary malignancy [PM]) and the SPM affects cancer-specific
      survival (CSS). METHODS: A multivariate Cox proportional hazards regression with
      Surveillance, Epidemiology, and End Results data for 13 regions from 1992 to 2008
      was used to ascertain whether the latency time (1-5 vs >= 6 years) to the
      development of an SPM affected the CSS and overall survival with respect to
      either the PM or SPM for AYAs with common SPMs. RESULTS: The majority of 1515
      AYAs with an SPM had their PM diagnosed between the ages of 26 and 39 years
      (74.2%) and an SPM diagnosed within 1 to 5 years (72.9%) of the PM's diagnosis.
      Overall, AYAs that developed an SPM 1 to 5 years after the diagnosis (vs >= 6
      years) had an increased risk of death from cancer (hazard ratio [HR], 2.52; 95%
      confidence interval [CI], 1.92-3.29) as well as any cause (HR, 2.60; 95% CI, 2.04
      3.32). Specifically, for AYAs with an SPM that was leukemia or a colorectal,
      breast, or central nervous system malignancy, a shorter latency time (1-5 years)
      from their PM diagnosis was associated with an overall significantly increased
      risk of death (2.6-fold) from either their PM or that particular SPM. However,
      latency did not appear to affect the CSS with respect to either the PM or SPM for
      AYA patients with a lymphoma or sarcoma SPM. CONCLUSIONS: Most AYAs who develop
      an SPM do so within 1 to 5 years of their primary cancer diagnosis, and they have
      an increased risk of death from cancer in comparison with AYAs with an SPM
      developing after longer survivorship intervals. Cancer 2018;124:1260-8. (c) 2017
      American Cancer Society.

PMID- 29205298
TI  - Growing competitive or tolerant? Significance of apical dominance in the
      overcompensating herb Gentianella campestris.
AB  - As a compensatory response to herbivory, plants may branch vigorously when the
      growth of dormant meristems is triggered by shoot damage. Undamaged plants, on
      the other hand, often restrain branching, and this limitation on growth can be
      considered a cost of tolerance to herbivory. Restrained branching is caused by
      apical dominance and may, alternatively, be associated with fitness benefits in
      competitive environments that favor fast vertical growth. To test these
      hypotheses regarding selection for restrained branching, we compared the
      performance of two subspecies of the biennial grassland herb Gentianella
      campestris; the tall, apically dominant ssp. campestris and the short, multi
      stemmed ssp. islandica, which shows reduced apical dominance. For both
      subspecies, we manipulated the height of surrounding vegetation (competition) and
      damage intensity in grasslands of differing productivity (high, medium, low), and
      examined population growth rates using matrix population models combined with
      life table response experiments. In the absence of damage, ssp. campestris
      exhibited a higher population growth rate than ssp. islandica in the tallest
      vegetation, however with the growth rate still being below one. In the medium and
      low productivity environments where the vegetation was shorter, the population
      growth rate of ssp. islandica was considerably higher than that of ssp.
      campestris as long as no more than about 50% of the plants were damaged. When
      plants were damaged, the apically dominant ssp. campestris showed a positive
      population growth rate (lambda > 1) and often overcompensatory seed production in
      all productivity levels, while ssp. islandica showed no compensation and
      therefore the population was predicted to decline (lambda < 1). We conclude that
      restrained branching in Gentianella cannot be selected for by competition alone,
      but that episodes of apical damage are required to maintain the trait.
      Furthermore, because of the costs of restrained branching, apical dominance
      should be selected against in grasslands where competition and disturbance are
      low.

PMID- 29205297
TI  - Meta-analysis of the procedural risks of carotid endarterectomy and carotid
      artery stenting over time.
AB  - BACKGROUND: Stroke/death rates within 30 days of carotid endarterectomy (CEA) and
      carotid artery stenting (CAS) in RCTs inform current clinical guidelines.
      However, the risks may have changed in recent years with wider use of effective
      stroke prevention therapies, especially statins, improved patient selection and
      growing operator expertise. The aim of this study was to investigate whether the
      procedural stroke/death risks from CEA and CAS have changed over time. METHODS:
      MEDLINE and Embase were searched systematically from inception to May 2016 for
      observational cohort studies of CEA and CAS. Studies included reported on more
      than 1000 patients, with 30-day outcomes after the procedure according to
      patients' symptom status (recent stroke or transient ischaemic attack).
      Restricted maximum likelihood random-effects and meta-regressions methods were
      used to synthesize procedural stroke/death rates of CEA and CAS according to year
      of study recruitment completion. RESULTS: Fifty-one studies, including 223 313
      patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural
      stroke/death risks of CEA decreased over time in symptomatic and asymptomatic
      patients. Risks were substantially lower in studies completing recruitment in
      2005 or later, both in symptomatic (5.11 per cent before 2005 versus 2.68 per
      cent from 2005 onwards; P = 0.002) and asymptomatic (3.17 versus 1.50 per cent; P
      < 0.001) patients. Procedural stroke/death rates of CAS did not change
      significantly over time (4.77 per cent among symptomatic and 2.59 per cent among
      asymptomatic patients). There was substantial heterogeneity in event rates and
      recruitment periods were long. CONCLUSIONS: Risks of procedural stroke/death
      following CEA appear to have decreased substantially. There was no evidence of a
      change in stroke/death rates following CAS.

PMID- 29205300
TI  - Cervical cancer survival in the United States by race and stage (2001-2009):
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: Overall, cervical cancer survival in the United States has been
      reported to be among the highest in the world, despite slight decreases over the
      last decade. Objective of the current study was to describe cervical cancer
      survival trends among US women and examine differences by race and stage.
      METHODS: This study used data from the CONCORD-2 study to compare survival among
      women (aged 15-99 years) diagnosed in 37 states covering 80% of the US
      population. Survival was adjusted for background mortality (net survival) with
      state- and race-specific life tables and was age-standardized with the
      International Cancer Survival Standard weights. Five-year survival was compared
      by race (all races, blacks, and whites). Two time periods, 2001-2003 and 2004
      2009, were considered because of changes in how the staging variable was
      collected. RESULTS: From 2001 to 2009, 90,620 women were diagnosed with invasive
      cervical cancer. The proportion of cancers diagnosed at a regional or distant
      stage increased over time in most states. Overall, the 5-year survival was 63.5%
      in 2001-2003 and 62.8% in 2004-2009. The survival was lower for black women
      versus white women in both calendar periods and in most states; black women had a
      higher proportion of distant-stage cancers. CONCLUSIONS: The stability of the
      overall survival over time and the persistent differences in survival between
      white and black women in all US states suggest that there is a need for targeted
      interventions and improved access to screening, timely treatment, and follow-up
      care, especially among black women. Cancer 2017;123:5119-37. Published 2017. This
      article is a U.S. Government work and is in the public domain in the USA.

PMID- 29205301
TI  - Public health surveillance of cancer survival in the United States and worldwide:
      The contribution of the CONCORD programme.
AB  - CONCORD is a programme for the global surveillance of cancer survival. In 2015,
      the second cycle of the program (CONCORD-2) established long-term surveillance of
      cancer survival worldwide, for the first time, in the largest cancer survival
      study published to date. CONCORD-2 provided cancer survival trends for 25,676,887
      patients diagnosed during the 15-year period between 1995 and 2009 with 1 of 10
      common cancers that collectively represented 63% of the global cancer burden in
      2009. Herein, the authors summarize the past, describe the present, and outline
      the future of the CONCORD programme. They discuss the difference between
      population-based studies and clinical trials, and review the importance of
      international comparisons of population-based cancer survival. This study will
      focus on the United States. The authors explain why population-based survival
      estimates are crucial for driving effective cancer control strategies to reduce
      the wide and persistent disparities in cancer survival between white and black
      patients, which are likely to be attributable to differences in access to early
      diagnosis and optimal treatment. Cancer 2017;123:4977-81. Published 2017. This
      article is a U.S. Government work and is in the public domain in the USA.

PMID- 29205299
TI  - Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in
      Europe: A Modified Delphi Study.
AB  - Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is
      necessary to ensure that the prescribing competency of future doctors is of a
      uniform high standard. As there are currently no uniform requirements, our aim
      was to achieve consensus on key learning outcomes for undergraduate CPT education
      in Europe. We used a modified Delphi method consisting of three questionnaire
      rounds and a panel meeting. A total of 129 experts from 27 European countries
      were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all
      three questionnaire rounds, and 33 experts (26%) attended the meeting. 232
      learning outcomes from the original list, 15 newly suggested and 5 rephrased
      outcomes were included. These 252 learning outcomes should be included in
      undergraduate CPT curricula to ensure that European graduates are able to
      prescribe safely and effectively. We provide a blueprint of a European core
      curriculum describing when and how the learning outcomes might be acquired.

PMID- 29205303
TI  - The essential role of population-based cancer survival in cancer control in the
      United States.

PMID- 29205302
TI  - Population-based cancer survival in the United States: Data, quality control, and
      statistical methods.
AB  - BACKGROUND: Robust comparisons of population-based cancer survival estimates
      require tight adherence to the study protocol, standardized quality control,
      appropriate life tables of background mortality, and centralized analysis. The
      CONCORD program established worldwide surveillance of population-based cancer
      survival in 2015, analyzing individual data on 26 million patients (including 10
      million US patients) diagnosed between 1995 and 2009 with 1 of 10 common
      malignancies. METHODS: In this Cancer supplement, we analyzed data from 37 state
      cancer registries that participated in the second cycle of the CONCORD program
      (CONCORD-2), covering approximately 80% of the US population. Data quality checks
      were performed in 3 consecutive phases: protocol adherence, exclusions, and
      editorial checks. One-, 3-, and 5-year age-standardized net survival was
      estimated using the Pohar Perme estimator and state- and race-specific life
      tables of all-cause mortality for each year. The cohort approach was adopted for
      patients diagnosed between 2001 and 2003, and the complete approach for patients
      diagnosed between 2004 and 2009. RESULTS: Articles in this supplement report
      population coverage, data quality indicators, and age-standardized 5-year net
      survival by state, race, and stage at diagnosis. Examples of tables, bar charts,
      and funnel plots are provided in this article. CONCLUSIONS: Population-based
      cancer survival is a key measure of the overall effectiveness of services in
      providing equitable health care. The high quality of US cancer registry data, 80%
      population coverage, and use of an unbiased net survival estimator ensure that
      the survival trends reported in this supplement are robustly comparable by race
      and state. The results can be used by policymakers to identify and address
      inequities in cancer survival in each state and for the United States nationally.
      Cancer 2017;123:4982-93. Published 2017. This article is a U.S. Government work
      and is in the public domain in the USA.

PMID- 29205304
TI  - Colon cancer survival in the United States by race and stage (2001-2009):
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: In the first CONCORD study (2008), 5-year survival for patients
      diagnosed with colon cancer between 1990 and 1994 in the United States was among
      the highest in the world (60%), but there were large racial disparities in most
      participating states. The CONCORD-2 study (2015) enabled the examination of
      survival trends between 1995 and 2009 for US states by race and stage. METHODS:
      The authors analyzed data from 37 state population-based cancer registries,
      covering approximately 80% of the US population, for patients who were diagnosed
      with colon cancer between 2001 and 2009 and were followed through 2009. Survival
      up to 5 years was corrected for background mortality (net survival) using state
      specific and race-specific life tables and age-standardized using the
      International Cancer Survival Standard weights. Survival is presented by race
      (all, black, white), stage, state, and calendar period (2001-2003 and 2004-2009)
      to account for changes in methods used to collect stage. RESULTS: Five-year net
      survival increased by 0.9%, from 63.7% between 2001 and 2003 to 64.6% between
      2004 and 2009. More black than white patients were diagnosed with distant-stage
      disease between 2001 and 2003 (21.5% vs 17.2%) and between 2004 and 2009 (23.3%
      vs 18.8%). Survival improved for both blacks and whites, but 5-year net survival
      was 9-10% lower for blacks than for whites both between 2001 and 2003 (54.7% vs
      64.5%) and between 2004 and 2009 (56.6% vs 65.4%). The absolute difference
      between blacks and whites decreased by only 1% during the decade. CONCLUSIONS:
      Five-year net survival from colon cancer increased slightly over time. Survival
      among blacks diagnosed between 2004 and 2009 had still not reached the level of
      that among whites diagnosed between 1990 and 1994, some 15 to 20 years earlier.
      These findings suggest a need for more targeted efforts to improve screening and
      to ensure timely, appropriate treatment, especially for blacks, to reduce this
      large and persistent disparity in survival. Cancer 2017;123:5014-36. Published
      2017. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 29205305
TI  - Lung cancer survival in the United States by race and stage (2001-2009): Findings
      from the CONCORD-2 study.
AB  - BACKGROUND: Results from the second CONCORD study (CONCORD-2) indicated that 5
      year net survival for lung cancer was low (range, 10%-20%) between 1995 and 2009
      in most countries, including the United States, which was at the higher end of
      this range. METHODS: Data from CONCORD-2 were used to analyze net survival among
      patients with lung cancer (aged 15-99 years) who were diagnosed in 37 states
      covering 80% of the US population. Survival was corrected for background
      mortality using state-specific and race-specific life tables and age-standardized
      using International Cancer Survival Standard weights. Net survival was estimated
      for patients diagnosed between 2001 and 2003 and between 2004 and 2009 at 1, 3,
      and 5 years after diagnosis by race (all races, black, and white); Surveillance,
      Epidemiology, and End Results Summary Stage 2000; and US state. RESULTS: Five
      year net survival increased from 16.4% (95% confidence interval, 16.3%-16.5%) for
      patients diagnosed 2001-2003 to 19.0% (18.8%-19.1%) for those diagnosed 2004
      2009, with increases in most states and among both blacks and whites. Between
      2004 and 2009, 5-year survival was lower among blacks (14.9%) than among whites
      (19.4%) and ranged by state from 14.5% to 25.2%. CONCLUSIONS: Lung cancer
      survival improved slightly between the periods 2001-2003 and 2004-2009 but was
      still low, with variation between states, and persistently lower survival among
      blacks than whites. Efforts to control well established risk factors would be
      expected to have the greatest impact on reducing the burden of lung cancer, and
      efforts to ensure that all patients receive timely and appropriate treatment
      should reduce the differences in survival by race and state. Cancer 2017;123:5079
      99. Published 2017. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 29205306
TI  - Liver cancer survival in the United States by race and stage (2001-2009):
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: Worldwide, liver cancer is a leading cause of death for both men and
      women. The number of Americans who are diagnosed with and die of liver cancer has
      been rising slowly each year. Using data from the CONCORD-2 study, this study
      examined population-based survival by state, race, and stage at diagnosis.
      METHODS: Data from 37 statewide registries, which covered 81% of the US
      population, for patients diagnosed during 2001-2009 were analyzed. Survival up to
      5 years was adjusted for background mortality (net survival) with state- and race
      specific life tables, and it was age-standardized with the International Cancer
      Survival Standard weights. RESULTS: Liver cancer was diagnosed overall more often
      at the localized stage, with blacks being more often diagnosed at distant and
      regional stages than whites. 5-year net survival was 12.2% in 2001-2003 and 14.8%
      in 2004-2009. Whites had higher survival than blacks in both calendar periods
      (11.7% vs 9.1% and 14.3% vs 11.4%, respectively). During 2004-2009, 5-year
      survival was 25.7% for localized-stage disease, 9.5% for regional-stage disease,
      and 3.5% for distant-stage disease. CONCLUSIONS: Some progress has occurred in
      survival for patients with liver cancer, but 5-year survival remains low, even
      for those diagnosed at the localized stage. Efforts directed at controlling well
      established risk factors such as hepatitis B may have the greatest impact on
      reducing the burden of liver cancer in the United States. Cancer 2017;123:5059
      78. Published 2017. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 29205307
TI  - The history and use of cancer registry data by public health cancer control
      programs in the United States.
AB  - Because cancer registry data provide a census of cancer cases, registry data can
      be used to: 1) define and monitor cancer incidence at the local, state, and
      national levels; 2) investigate patterns of cancer treatment; and 3) evaluate the
      effectiveness of public health efforts to prevent cancer cases and improve cancer
      survival. The purpose of this article is to provide a broad overview of the
      history of cancer surveillance programs in the United States, and illustrate the
      expanding ways in which cancer surveillance data are being made available and
      contributing to cancer control programs. The article describes the building of
      the cancer registry infrastructure and the successful coordination of efforts
      among the 2 federal agencies that support cancer registry programs, the Centers
      for Disease Control and Prevention and the National Cancer Institute, and the
      North American Association of Central Cancer Registries. The major US cancer
      control programs also are described, including the National Comprehensive Cancer
      Control Program, the National Breast and Cervical Cancer Early Detection Program,
      and the Colorectal Cancer Control Program. This overview illustrates how cancer
      registry data can inform public health actions to reduce disparities in cancer
      outcomes and may be instructional for a variety of cancer control professionals
      in the United States and in other countries. Cancer 2017;123:4969-76. Published
      2017. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 29205308
TI  - Rectal cancer survival in the United States by race and stage, 2001 to 2009:
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: In the first CONCORD study, 5-year survival for patients with
      diagnosed with rectal cancer between 1990 and 1994 was <60%, with large racial
      disparities noted in the majority of participating states. We have updated these
      findings to 2009 by examining population-based survival by stage of disease at
      the time of diagnosis, race, and calendar period. METHODS: Data from the CONCORD
      2 study were used to compare survival among individuals aged 15 to 99 years who
      were diagnosed in 37 states encompassing up to 80% of the US population. We
      estimated net survival up to 5 years after diagnosis correcting for background
      mortality with state-specific and race-specific life table. Survival estimates
      were age-standardized with the International Cancer Survival Standard weights. We
      present survival estimates by race (all, black, and white) for 2001 through 2003
      and 2004 through 2009 to account for changes in collecting the data for
      Surveillance, Epidemiology, and End Results Summary Stage 2000. RESULTS: There
      was a small increase in 1-year, 3-year, and 5-year net survival between 2001-2003
      (84.6%, 70.7%, and 63.2%, respectively), and 2004-2009 (85.1%, 71.5%, and 64.1%,
      respectively). Black individuals were found to have lower 1-year, 3-year, and 5
      year survival than white individuals in both periods; the absolute difference in
      survival between black and white individuals declined only for 5-year survival.
      Black patients had lower 5-year survival than whites at each stage at the time of
      diagnosis in both time periods. CONCLUSIONS: There was little improvement noted
      in net survival for patients with rectal cancer, with persistent disparities
      noted between black and white individuals. Additional investigation is needed to
      identify and implement effective interventions to ensure the consistent and
      equitable use of high-quality screening, diagnosis, and treatment to improve
      survival for patients with rectal cancer. Cancer 2017;123:5037-58. Published
      2017. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 29205309
TI  - Population-based cancer survival (2001 to 2009) in the United States: Findings
      from the CONCORD-2 study.

PMID- 29205310
TI  - Stomach cancer survival in the United States by race and stage (2001-2009):
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: Stomach cancer was a leading cause of cancer-related deaths early in
      the 20th century and has steadily declined over the last century in the United
      States. Although incidence and death rates are now low, stomach cancer remains an
      important cause of morbidity and mortality in black, Asian and Pacific Islander,
      and American Indian/Alaska Native populations. METHODS: Data from the CONCORD-2
      study were used to analyze stomach cancer survival among males and females aged
      15 to 99 years who were diagnosed in 37 states covering 80% of the US population.
      Survival analyses were corrected for background mortality using state-specific
      and race-specific (white and black) life tables and age-standardized using the
      International Cancer Survival Standard weights. Net survival is presented up to 5
      years after diagnosis by race (all, black, and white) for 2001 through 2003 and
      2004 through 2009 to account for changes in collecting Surveillance,
      Epidemiology, and End Results Summary Stage 2000 data from 2004. RESULTS: Almost
      one-third of stomach cancers were diagnosed at a distant stage among both whites
      and blacks. Age-standardized 5-year net survival increased between 2001 to 2003
      and 2004 to 2009 (26.1% and 29%, respectively), and no differences were observed
      by race. The 1-year, 3-year, and 5-year survival estimates were 53.1%, 33.8%, and
      29%, respectively. Survival improved in most states. Survival by stage was 64%
      (local), 28.2% (regional), and 5.3% (distant). CONCLUSIONS: The current results
      indicate high fatality for stomach cancer, especially soon after diagnosis.
      Although improvements in stomach cancer survival were observed, survival remained
      relatively low for both blacks and whites. Primary prevention through the control
      of well-established risk factors would be expected to have the greatest impact on
      further reducing deaths from stomach cancer. Cancer 2017;123:4994-5013. Published
      2017. This article is a U.S. Government work and is in the public domain in the
      USA.

PMID- 29205311
TI  - Disparities in breast cancer survival in the United States (2001-2009): Findings
      from the CONCORD-2 study.
AB  - BACKGROUND: Reducing breast cancer incidence and achieving equity in breast
      cancer outcomes remains a priority for public health practitioners, health care
      providers, policy makers, and health advocates. Monitoring breast cancer survival
      can help evaluate the effectiveness of health services, quantify inequities in
      outcomes between states or population subgroups, and inform efforts to improve
      the effectiveness of cancer management and treatment. METHODS: We analyzed breast
      cancer survival using individual patient records from 37 statewide registries
      that participated in the CONCORD-2 study, covering approximately 80% of the US
      population. Females were diagnosed between 2001 and 2009 and were followed
      through December 31, 2009. Age-standardized net survival at 1 year, 3 years, and
      5 years after diagnosis was estimated by state, race (white, black), stage at
      diagnosis, and calendar period (2001-2003 and 2004-2009). RESULTS: Overall, 5
      year breast cancer net survival was very high (88.2%). Survival remained
      remarkably high from 2001 through 2009. Between 2001 and 2003, survival was 89.1%
      for white females and 76.9% for black females. Between 2004 and 2009, survival
      was 89.6% for white females and 78.4% for black females. CONCLUSIONS: Breast
      cancer survival was more than 10 percentage points lower for black females than
      for white females, and this difference persisted over time. Reducing racial
      disparities in survival remains a challenge that requires broad, coordinated
      efforts at the federal, state, and local levels. Monitoring trends in breast
      cancer survival can highlight populations in need of improved cancer management
      and treatment. Cancer 2017;123:5100-18. Published 2017. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 29205313
TI  - Prostate cancer survival in the United States by race and stage (2001-2009):
      Findings from the CONCORD-2 study.
AB  - BACKGROUND: The 5-year relative survival for prostate cancers diagnosed between
      1990 and 1994 in the United States was very high (92%); however, survival in
      black males was 7% lower compared with white males. The authors updated these
      findings and examined survival by stage and race. METHODS: The authors used data
      from the CONCORD-2 study for males (ages 15-99 years) who were diagnosed with
      prostate cancer in 37 states, covering 80% of the US population. Survival was
      adjusted for background mortality (net survival) using state-specific and race
      specific life tables and was age-standardized. Data were presented for 2001
      through 2003 and 2004 through 2009 to account for changes in collecting SEER
      Summary Stage 2000. RESULTS: Among the 1,527,602 prostate cancers diagnosed
      between 2001 and 2009, the proportion of localized cases increased from 73% to
      77% in black males and from 77% to 79% in white males. Although the proportion of
      distant-stage cases was higher among black males than among white males, they
      represented less than 6% of cases in both groups between 2004 and 2009. Net
      survival exceeded 99% for localized stage between 2004 and 2009 in both racial
      groups. Overall, and in most states, 5-year net survival exceeded 95%.
      CONCLUSIONS: Prostate cancer survival has increased since the first CONCORD
      study, and the racial gap has narrowed. Earlier detection of localized cancers
      likely contributed to this finding. However, racial disparities also were
      observed in overall survival. To help understand which factors might contribute
      to the persistence of this disparity, states could use local data to explore
      sociodemographic characteristics, such as survivors' health insurance status,
      health literacy, treatment decision-making processes, and treatment preferences.
      Cancer 2017;123:5160-77. Published 2017. This article is a U.S. Government work
      and is in the public domain in the USA.

PMID- 29205312
TI  - Disparities in ovarian cancer survival in the United States (2001-2009): Findings
      from the CONCORD-2 study.
AB  - BACKGROUND: Ovarian cancer is the fifth leading cause of cancer death among women
      in the United States. This study reports ovarian cancer survival by state, race,
      and stage at diagnosis using data from the CONCORD-2 study, the largest and most
      geographically comprehensive, population-based survival study to date. METHODS:
      Data from women diagnosed with ovarian cancer between 2001 and 2009 from 37
      states, covering 80% of the US population, were used in all analyses. Survival
      was estimated up to 5 years and was age standardized and adjusted for background
      mortality (net survival) using state-specific and race-specific life tables.
      RESULTS: Among the 172,849 ovarian cancers diagnosed between 2001 and 2009, more
      than one-half were diagnosed at distant stage. Five-year net survival was 39.6%
      between 2001 and 2003 and 41% between 2004 and 2009. Black women had consistently
      worse survival compared with white women (29.6% from 2001-2003 and 31.1% from
      2004-2009), despite similar stage distributions. Stage-specific survival for all
      races combined between 2004 and 2009 was 86.4% for localized stage, 60.9% for
      regional stage, and 27.4% for distant stage. CONCLUSIONS: The current data
      demonstrate a large and persistent disparity in ovarian cancer survival among
      black women compared with white women in most states. Clinical and public health
      efforts that ensure all women who are diagnosed with ovarian cancer receive
      appropriate, guidelines-based treatment may help to decrease these disparities.
      Future research that focuses on the development of new methods or modalities to
      detect ovarian cancer at early stages, when survival is relatively high, will
      likely improve overall US ovarian cancer survival. Cancer 2017;123:5138-59.
      Published 2017. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 29205314
TI  - Survival among children diagnosed with acute lymphoblastic leukemia in the United
      States, by race and age, 2001 to 2009: Findings from the CONCORD-2 study.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood
      malignancy. This report describes the survival of children with ALL in the United
      States using the most comprehensive and up-to-date cancer registry data. METHODS:
      Data from 37 state cancer registries that cover approximately 80% of the US
      population were used. Age-standardized survival up to 5 years was estimated for
      children aged 0-14 years who were diagnosed with ALL during 2 periods (2001-2003
      and 2004-2009). RESULTS: In total, 17,500 children with ALL were included. The
      pooled age-standardized net survival estimates for all US registries combined
      were 95% at 1 year, 90% at 3 years, and 86% at 5 years for children diagnosed
      during 2001-2003, and 96%, 91%, and 88%, respectively, for those diagnosed during
      2004-2009. Black children who were diagnosed during 2001-2003 had lower 5-year
      survival (84%) than white children (87%) and had less improvement in survival by
      2004-2009. For those diagnosed during 2004-2009, the 1-year and 5-year survival
      estimates were 96% and 89%, respectively, for white children and 96% and 84%,
      respectively, for black children. During 2004-2009, survival was highest among
      children aged 1 to 4 years (95%) and lowest among children aged <1 year (60%).
      CONCLUSIONS: The current results indicate that overall net survival from
      childhood ALL in the United States is high, but disparities by race still exist,
      especially beyond the first year after diagnosis. Clinical and public health
      strategies are needed to improve health care access, clinical trial enrollment,
      treatment, and survivorship care for children with ALL. Cancer 2017;123:5178-89.
      Published 2017. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 29205316
TI  - The "jack-in-the-box" stamens of Heliconia wagneriana (Heliconiaceae).

PMID- 29205317
TI  - Fitness consequences of occasional outcrossing in a functionally asexual plant
      (Oenothera biennis).
AB  - Many clonal organisms occasionally outcross, but the long-term consequences of
      such infrequent events are often unknown. During five years, representing three
      to five plant generations, we followed 16 experimental field populations of the
      forb, Oenothera biennis, originally planted with the same 18 original genotypes.
      Oenothera biennis usually self fertilizes, which, due to its genetic system
      (permanent translocation heterozygosity), results in seeds that are clones of the
      maternal plant. However, rare outcrossing produces genetically novel offspring
      (but without recombination or increased heterozygosity). We sought to understand
      whether novel genotypes produced through natural outcrossing had greater
      fecundity or different multigenerational dynamics compared to our original
      genotypes. We further assessed whether any differences in fitness or abundances
      through time between original and novel genotypes were exaggerated in the
      presence vs. absence of insect herbivores. Over the course of the experiment, we
      genotyped >12,500 plants using microsatellite DNA markers to identify and track
      the frequency of specific genotypes and estimated fecundity on a subset (>3,000)
      of plants. The effective outcrossing rate was 7.3% in the first year and
      ultimately 50% of the plants were of outcrossed origin by the final year of the
      experiment. Lifetime fruit production per plant was on average 32% higher across
      all novel genotypes produced via outcrossing compared to the original genotypes,
      and this fecundity advantage was significantly enhanced in populations lacking
      herbivores. Among 43 novel genotypes that were abundant enough to phenotype with
      replication, plants produced nearly 30% more fruits than the average of their
      specific two parental genotypes, and marginally more fruits (8%) than their most
      fecund parent. Mean per capita fecundity of novel genotypes predicted their
      relative frequencies at the end of the experiment. Novel genotypes increased more
      dramatically in herbivore-present compared to suppressed populations (45% vs. 27%
      of all plants), countering the increased competition from dandelions (Taraxacum
      officinale) that resulted from herbivore suppression. Increased interspecific
      competition likely also lead to the lower realized fitness of novel vs. original
      genotypes in herbivore-suppressed populations. These results demonstrate that
      rare outcrossing and the generation of novel genotypes can create high-fecundity
      progeny, with the biotic environment influencing the dynamical outcome of such
      advantages.

PMID- 29205318
TI  - Development of Episodic Prospection: Factors Underlying Improvements in Middle
      and Late Childhood.
AB  - Episodic prospection is the mental simulation of a personal future event in rich
      contextual detail. This study examined age-related differences in episodic
      prospection in 5- to 11-year-olds and adults (N = 157), as well as factors that
      may contribute to developmental improvements. Participants' narratives of past,
      future, and make-believe events were coded for episodic content, and self-concept
      coherence (i.e., how coherently an individual sees himself or herself) and
      narrative ability were tested as predictors of episodic prospection. Although all
      ages provided less episodic content for future event narratives, age-related
      improvements were observed across childhood, suggesting future event generation
      is particularly difficult for children. Self-concept coherence and narrative
      ability each independently predicted the episodic content of 5- and 7-year-olds'
      future event narratives.

PMID- 29205315
TI  - Repository corticotrophin injection exerts direct acute effects on human B cell
      gene expression distinct from the actions of glucocorticoids.
AB  - Repository corticotrophin injection (RCI, H.P Acthar(r) gel) has been approved
      for use in the management of multiple autoimmune and inflammatory diseases for
      more than a half-century, but its mechanism of action is not well understood. We
      used RNA-Seq methods to define RCI-regulated mRNAs in cultured human B cells
      under conditions of activation by interleukin (IL)-4 and CD40 ligand. Following
      IL-4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA
      transcripts and down-regulation of 80 unique mRNAs. The effect on these RNA
      levels was dose-dependent for RCI and was distinct from changes in mRNA
      expression induced by treatment with a potent synthetic glucocorticoid. RCI down
      regulated mRNAs were observed to include a significant over-representation of
      genes critical for B cell proliferation under activating conditions. These data
      confirm that RCI exerts direct effects on human B cells to modulate mRNA
      expression in specific pathways of importance to B cell function and that, at the
      molecular level, the effects of RCI are distinct from those exerted by
      glucocorticoids.

PMID- 29205319
TI  - Atypical presentations of dysembryoplastic neuroepithelial tumors.
AB  - Dysembryoplastic neuroepithelial tumors (DNETs) are World Health Organization
      grade 1 neoplasms, typically present as isolated cortical lesions with no
      associated edema. We present 3 rare cases of DNETs that were atypical in location
      (all were subcortical and 1 was bilateral), 2 of which displayed substantial
      growth over time. All 3 cases presented with seizures that were not well
      controlled on medications, followed by a successful cure of the epilepsy when
      these lesions were removed. These cases uniquely illustrate that DNETs can be
      present throughout the brain and may generate seizures even in a subcortical
      location, possibly due to containing neurons with the potential for aberrant
      microcircuitry. The slow, nonmalignant proliferation of these lesions may engage
      epileptogenic networks, leading to the onset of seizures. These cases carry
      implications for the management of these surgically treatable lesions. Thus far,
      there have only been a handful of cases of growth reported in nonmalignant DNETs,
      and 2 of these cases displayed growth over the interval of monitoring.

PMID- 29205320
TI  - Effect of mother's voice on neonatal respiratory activity and EEG delta
      amplitude.
AB  - While the influence of the mother's voice on neonatal heart-rate response and its
      relevant activity on cerebral cortex and the autonomic nervous system (ANS) are
      well known, few studies have assessed its influence on respiratory activity. We
      investigated the relationship among the respiration rate, the delta wave
      amplitudes through electroencephalography, and the basal state of ANS through the
      respiratory variability index while 22 full-term neonates hear their mother's
      voice and an unknown voice. It was found that when respiratory variability was
      large, a transient (<5 s) change in respiration rates was observed in response to
      an unknown voice, while a greater increase in the delta wave amplitude was
      observed in the frontal lobe than the parietal one in response to the mother's
      voice. Conversely, when respiratory variability was small, a sustained increase
      (>10 s) in respiration rates was observed in response to the mother's voice,
      while a greater increase in the delta wave amplitude was found in both the
      frontal and parietal lobes. These results suggest that the basal state of ANS
      influences the latency of increases in respiration rates. Furthermore, induced by
      the mother's voice, transient increases in respiration rates are reduced in
      association with frontal lobe activity, and sustained increases in respiration
      rates are promoted in association with frontal and parietal lobe activities.

PMID- 29205321
TI  - Conditional survival of patients with gastric cancer who undergo curative
      resection: A multi-institutional analysis in China.
AB  - BACKGROUND: Conditional survival estimates, which take into consideration the
      changing risk with increasing survival time, provide a dynamic survival
      probability and more accurate survival information for clinician decision making.
      The objective of the current study was to evaluate the conditional disease
      specific survival (DSS) for patients with gastric cancer who underwent curative
      surgery in China. METHODS: In total, 7658 patients with gastric cancer from a
      multi-institutional cohort in China were included in the analyses. Actuarial DSS
      was estimated using the Kaplan-Meier method. Three-year conditional DSS (CDS3 )
      of patients who had already survived for x years was estimated as CDS3 = DSS(x +
      3)/DSS(x). Cox proportional hazards regression analyses were used to identify the
      factors related to DSS. RESULTS: The 1-year, 3-year, and 5-year actuarial DSS
      rates were 88.2%, 64.5%, and 54.6%, respectively. By using CDS estimates, the
      probabilities that patients would remain alive for an additional 3 years given
      that they had already survived for 1, 3, and 5 years were 66.6%, 80.2%, and
      88.3%, respectively. Patients who had unfavorable tumor characteristics diagnosed
      initially at surgery had the greatest improvement in CDS and the largest survival
      gap between actuarial DSS and CDS. CONCLUSIONS: The current results indicate that
      CDS estimates for Chinese patients with gastric cancer who underwent surgery were
      dynamic and increased with time elapsed. Patients who had unfavorable tumor
      characteristics had the greatest improvement in CDS. This valuable information
      could provide more a precise evaluation of long-term prognosis and may serve as
      an important prognostic index in clinical practice. Cancer 2018;124:916-24. (c)
      2017 American Cancer Society.

PMID- 29205323
TI  - Response: Neurocysticercosis and epilepsy.

PMID- 29205322
TI  - A targeted sequencing panel identifies rare damaging variants in multiple genes
      in the cranial neural tube defect, anencephaly.
AB  - Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or
      at birth, whereas lower spinal defects (spina bifida) may lead to lifelong
      neurological handicap. Collectively, NTDs rank among the most common birth
      defects worldwide. This study focuses on anencephaly, which despite having a
      similar frequency to spina bifida and being the most common type of NTD observed
      in mouse models, has had more limited inclusion in genetic studies. A genetic
      influence is strongly implicated in determining risk of NTDs and a molecular
      diagnosis is of fundamental importance to families both in terms of understanding
      the origin of the condition and for managing future pregnancies. Here we used a
      custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs
      (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome
      sequencing platform. After filtering and comparing to our in-house control exome
      database (N = 509), we identified 397 rare variants (minor allele frequency, MAF
      < 1%), 21 of which were previously unreported and predicted damaging. This
      included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense
      variations. Together with evidence for oligogenic inheritance, this study
      provides new information on the possible genetic causation of anencephaly.

PMID- 29205324
TI  - What proportion of cases of epilepsy are actually caused by neurocysticercosis?

PMID- 29205325
TI  - Couple-based Intervention for Depression: An Effectiveness Study in the National
      Health Service in England.
AB  - This study represents an effectiveness study and service evaluation of a
      cognitive behavioral, couple-based treatment for depression (BCT-D) provided in
      London services that are part of the "Improving Access to Psychological
      Therapies" (IAPT) program in England. Twenty-three therapists in community
      clinics were trained in BCT-D during a 5-day workshop, followed by monthly group
      supervision for 1 year. The BCT-D treatment outcome findings are based on 63
      couples in which at least one partner was depressed and elected to receive BCT-D.
      Eighty-five percent of couples also demonstrated relationship distress, and 49%
      of the nonclient partners also met caseness for depression or anxiety. Findings
      demonstrated a recovery rate of 57% with BCT-D, compared to 41% for all IAPT
      treatments for depression in London. Nonclient partners who met caseness
      demonstrated a 48% recovery rate with BCT-D, although they were not the focus of
      treatment. BCT-D was equally effective for clients regardless of the clinical
      status of the nonclient partner, suggesting its effectiveness in assisting both
      members of the couple simultaneously. Likewise, treatment was equally effective
      whether or not both partners reported relationship distress. The findings are
      promising regarding the successful application of BCT-D in routine clinical
      settings.

PMID- 29205326
TI  - Clinical Features, Familial History, and Migraine Precursors in Patients With
      Definite Vestibular Migraine: The VM-Phenotypes Projects.
AB  - OBJECTIVE: The aim of this work was to assess through a questionnaire the
      features of vertiginous episodes, accompanying symptoms, familial history, and
      migraine precursors in a sample of 252 subjects with a diagnosis of definite
      vestibular migraine. BACKGROUND: Migraine is a common neurological disorder
      characterized by episodic headaches with specific features. About two-thirds of
      cases run in families, and patients may refer symptoms occurring in infancy and
      childhood, defined as episodic syndromes that may be associated with migraine.
      Migraine is associated with episodic vertigo, called vestibular migraine, whose
      diagnosis mainly relies on clinical history showing a temporary association of
      symptoms. METHODS: In this cross-sectional multicentric study, 252 subjects were
      recruited in different centers; a senior specialist through a structured
      questionnaire assessed features of vestibular symptoms and accompanying symptoms.
      RESULTS: The age of onset of migraine was 23 years, while onset of vertigo was at
      38 years. One hundred and eighty-four subjects reported internal vertigo (73%),
      while 63 subjects (25%) reported external vertigo. The duration of vertigo
      attacks was less than 5 minutes in 58 subjects (23%), between 6 and 60 minutes in
      55 (21.8%), between 1 and 4 hours in 29 (11.5%), 5 and 24 hours in 44 (17.5%), up
      to 3 days in 14 (5.5%), and more than 3 days in seven (2.8%); 14 subjects (5.5%)
      referred attacks lasting from less than 5 minutes and up to 1 hour, nine (3.6%)
      referred attacks lasting from less than 5 minutes and up to 1 to 4 hours, six
      (2.4%) referred attacks lasting from less than 5 minutes and up to 5 to 24 hours,
      and five (2%) cases referred attacks lasting from less than 5 minutes and up to
      days. Among accompanying symptoms, patients referred the following usually
      occurring, in order of frequency: nausea (59.9%), photophobia (44.4%),
      phonophobia (38.9%), vomiting (17.8%), palpitations (11.5%), tinnitus (10.7%),
      fullness of the ear (8.7%), and hearing loss (4%). In total, 177 subjects
      referred a positive family history of migraine (70.2%), while 167 (66.3%)
      reported a positive family history of vertigo. In the sample, 69% of patients
      referred at least one of the pediatric precursors, in particular, 42.8% of
      subjects referred motion sickness. The age of onset of the first headache was
      lower in the subsample with a familial history of migraine than in the total
      sample. Among the pediatric precursors, benign paroxysmal vertigo - BPV, benign
      paroxysmal torticollis, and motion sickness were predictive of a lower age of
      onset of vertigo in adulthood; cyclic vomiting was predictive for vomiting during
      vertigo attacks in adults. CONCLUSIONS: Our results may indicate that vestibular
      symptoms in pediatric patients may act as a predisposing factor to develop
      vestibular migraine at an earlier age in adulthood.

PMID- 29205327
TI  - Social behaviour and gut microbiota in red-bellied lemurs (Eulemur rubriventer):
      In search of the role of immunity in the evolution of sociality.
AB  - Vertebrate gut microbiota form a key component of immunity and a dynamic link
      between an individual and the ecosystem. Microbiota might play a role in social
      systems as well, because microbes are transmitted during social contact and can
      affect host behaviour. Combining methods from behavioural and molecular research,
      we describe the relationship between social dynamics and gut microbiota of a
      group-living cooperative species of primate, the red-bellied lemur (Eulemur
      rubriventer). Specifically, we ask whether patterns of social contact (group
      membership, group size, position in social network, individual sociality) are
      associated with patterns of gut microbial composition (diversity and similarity)
      between individuals and across time. Red-bellied lemurs were found to have gut
      microbiota with slight temporal fluctuations and strong social group-specific
      composition. Contrary to expectations, individual sociality was negatively
      associated with gut microbial diversity. However, position within the social
      network predicted gut microbial composition. These results emphasize the role of
      the social environment in determining the microbiota of adult animals. Since
      social transmission of gut microbiota has the potential to enhance immunity,
      microbiota might have played an escalating role in the evolution of sociality.

PMID- 29205329
TI  - Women who undergo HPV testing receive earlier detection and treatment of cervical
      precancers.

PMID- 29205328
TI  - Quantitative analysis of hepatic macro- and microvascular alterations during
      cirrhogenesis in the rat.
AB  - Cirrhosis represents the end-stage of any persistent chronically active liver
      disease. It is characterized by the complete replacement of normal liver tissue
      by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The
      resulting angioarchitectural distortion contributes to an increasing intrahepatic
      vascular resistance, impeding liver perfusion and leading to portal hypertension.
      To date, knowledge on the dynamically evolving pathological changes of the
      hepatic vasculature during cirrhogenesis remains limited. More specifically,
      detailed anatomical data on the vascular adaptations during disease development
      is lacking. To address this need, we studied the 3D architecture of the hepatic
      vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was
      chemically induced with thioacetamide (TAA). At predefined time points, the
      hepatic vasculature was fixed and visualized using a combination of vascular
      corrosion casting and deep tissue microscopy. Three-dimensional reconstruction
      and data-fitting enabled cirrhogenic features to extracted at multiple scales,
      portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel,
      we noticed that regenerative nodules severely compressed pliant venous vessels
      from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly
      affected by this compression, with collapsed vessel segments severely reducing
      perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal
      degeneration, with sinusoids located near the surface being more affected than
      those in the middle of a liver lobe. Our data shed light on and quantify the
      evolving angioarchitecture during cirrhogenesis. These findings may prove helpful
      for future targeted invasive interventions.

PMID- 29205331
TI  - First person: Julie Vose, MD, MBA: The lymphoma specialist is focused on patients
      as well as organizational leadership.

PMID- 29205330
TI  - Secondhand smoke exposure declines among nonsmoking cancer survivors.

PMID- 29205333
TI  - Regulation of apical blebbing in the porcine epididymis.
AB  - Apical blebbing, a non-classical secretion mechanism, occurs in the mature
      porcine epididymis as part of its normal function. Proteins secreted by this
      mechanism contribute to the modification of the sperm plasma membrane during
      epididymal transit and are thought to contribute to acquisition of fertilizing
      ability. However, little is known about the regulation of this secretion
      mechanism in an in vivo model. Previous work demonstrated apical blebbing in the
      epididymis developed pubertally, suggesting androgens, sperm or other luminal
      factors regulated this process. Hence, the objective was to evaluate the
      hypothesized regulation of apical blebbing in the epididymis of pubertal boars by
      androgens and luminal factors. Androgen receptor blockade (flutamide) and
      surgical interventions (efferent duct ligation, orchidectomy or transection of
      the caput epididymis) were used to alter signaling, and the subsequent effects on
      apical blebbing were evaluated histologically. Apical blebbing was not altered by
      androgen receptor blockade with flutamide, but was significantly reduced 24 h
      after efferent duct ligation and after orchidectomy, treatments that eliminated
      luminal flow from the testis (P < 0.05). Like efferent duct ligation, epididymal
      transection altered luminal flow without removing the androgen source and
      significantly reduced the appearance of apical blebbing (P < 0.05). In
      conclusion, apical blebbing in the porcine epididymis appears to be regulated by
      luminal factors.

PMID- 29205334
TI  - Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer
      cell growth and angiogenic activity by inhibiting glucose uptake.
AB  - Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of
      antidiabetic agents that inhibit glucose reabsorption in the renal proximal
      tubules. Although a recent report demonstrated the potential ability of SGLT2-Is
      to attenuate cancer growth of SGLT2-expressing cancer cells, little is known
      about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we
      investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human
      liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and
      HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic
      stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2
      expressing Huh7 and HepG2 cells in a dose-dependent manner by inhibiting
      glycolytic metabolism including glucose uptake, lactate and intracellular ATP
      production. This agent also induced G2/M arrest and apoptosis with inhibited
      phosphorylation of ERK, p38 and AKT and cleavage of caspase3. Xenograft tumor
      growth assay showed that oral administration of canagliflozin (10 mg/kg/day)
      significantly reduced subcutaneous tumor burdens in a glycemic status-independent
      manner, and attenuated intratumor vascularization in Huh7- and HepG2-derived
      xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the
      increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular
      formation which were observed in Huh7 or HepG2 co-cultures. By contrast,
      canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2
      null HLE-derived xenograft models. These results indicate that SGLT2-I therapy is
      a potential new strategy for the treatment of HCC.

PMID- 29205335
TI  - Melanomacrophage functions in the liver of the caecilian Siphonops annulatus.
AB  - Melanomacrophages are phagocytes that synthesize melanin. They are found in the
      liver and spleen of ectothermic vertebrates, and in the kidney of fish. In
      agnathan and elasmobranch fish, melanomacrophages are seen as isolated cells, and
      forming clusters in all the other vertebrates. The natural phagocytic activity of
      melanomacrophages is poorly characterized, as most of the research works have
      focused on induced phagocytic activity only. Furthermore, little is known about
      amphibian melanomacrophages, mainly about those in caecilians - wormlike
      amphibians in the order of Gymnophiona, which is the least known group of
      terrestrial vertebrates. The present research work aimed at the structure and
      function of hepatic melanomacrophages of Siphonops annulatus, a species largely
      found in South America. We identified the role of these cells in the control of
      circulating basophils (pro-melanogenic cells), in the turnover of liver collagen
      stroma and in the hemocatheresis, interrelated physiological mechanisms.

PMID- 29205337
TI  - Prevention of the development of problem behavior: A laboratory model.
AB  - Few studies have isolated the preventive efficacy of common behavioral strategies
      like noncontingent reinforcement (NCR) and differential reinforcement of
      alternative behavior (DRA). The purpose of the current study was to develop and
      evaluate a laboratory model of these two problem behavior prevention strategies.
      Undergraduate students participated in a computer simulation, in which clicks to
      a designated area of the computer screen were analogous to the emergence of
      problem behavior. The responding of participants in a control group, who
      experienced a percentile schedule used to mimic the shaping of problem behavior,
      was compared to that of participants in two experimental groups, each with a
      history of either DRA or NCR. Between-subjects group comparisons showed that both
      intervention strategies were equally effective in the prevention of our analog to
      problem behavior when compared to the control group. The strengths and
      limitations of a laboratory model for prevention are discussed in light of recent
      applied work in this area.

PMID- 29205336
TI  - Trends in incidence, mortality and survival of penile squamous cell carcinoma in
      Norway 1956-2015.
AB  - We examine trends in incidence, mortality and survival of penile squamous cell
      carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer
      diagnosed in Norway during 1956-2015 were obtained from the Cancer Registry of
      Norway. Trends in age-standardized rates of penile SCC incidence, mortality and 5
      year relative survival were assessed by the annual percentage change statistic
      and joinpoint regression. A total of 1,596 penile cancer cases were diagnosed
      during 1956-2015, among which 1,474 (92.4%) were SCC. During 2011-2015, the age
      standardized incidence and mortality of penile SCC were 0.91 (95% confidence
      interval (CI): 0.78; 1.05) and 0.50 (0.42; 0.60) per 100,000, respectively, and
      the 5-year relative survival was 61.6% (41.9; 76.4). The incidence of SCC
      increased during 1956-2015, with an average annual percentage change (AAPC) of
      0.80% (0.46; 1.15). The increase was strongest among men diagnosed at a
      relatively early age (age<=64 years; AAPC: 1.47% (0.90; 2.05)). Mortality also
      increased over the study period (AAPC: 0.47% (0.10; 0.85)), whereas 5-year
      relative survival did not change (AAPC: 0.08% (-0.19; 0.36)). We conclude that
      the incidence of penile SCC has increased at a moderate and constant rate during
      1956-2015, and that the most consistent increase occurred among younger men.
      Mortality also increased during the study period. However, survival did not
      change, thus changes in diagnostics and treatment had little impact on survival
      from penile SCC. Since a substantial proportion of penile SCC is caused by human
      papillomavirus (HPV), the incidence increase may in part be attributed to
      increased exposure to HPV in the population.

PMID- 29205338
TI  - S1P receptor antagonists fingolimod and siponimod do not improve the outcome of
      experimental autoimmune myasthenia gravis mice after disease onset.
AB  - Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness
      and fatigue in the presence of circulating antibodies against components of the
      neuromuscular junction. Most patients have a good prognosis, but some are
      refractory to standard-of-care immunosuppressive treatment and suffer from
      recurrent myasthenic crises. Functional sphingosine-1-phosphate (S1P) antagonists
      like fingolimod and siponimod (BAF312) are successfully used for the treatment of
      multiple sclerosis, and fingolimod was shown to prevent the development of
      myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the
      standard model of MG. Here, we investigated whether fingolimod or siponimod
      improves outcome in EAMG mice when administered after disease onset, modeling the
      clinical setting in human MG. Both S1P antagonists inhibited lymphocyte egress,
      resulting in peripheral lymphopenia. After stimulation, there were differences in
      T-cell responses, but no change in either antibody titers or total or antigen
      specific plasma cell populations after treatment. Most importantly, disease
      incidence and severity were not influenced by fingolimod or siponimod therapy.
      Although fingolimod and siponimod did lead to subtle changes in T-cell responses,
      they had no significant effect on antibody titers and disease severity. In
      conclusion, our data show no evidence of a therapeutic potential for S1P receptor
      antagonists in MG treatment.

PMID- 29205339
TI  - Acne in late adolescence and risk of prostate cancer.
AB  - Accumulating evidence suggest that Propionibacterium acnes may play a role in
      prostate carcinogenesis, but data are so far limited and inconclusive. The aim of
      this population-based cohort study was therefore to test whether presence of acne
      vulgaris during late adolescence is associated with an increased risk of prostate
      cancer later in life. We identified a large cohort of young men born in Sweden
      between 1952 and 1956, who underwent mandatory assessment for military
      conscription around the age of 18 (n = 243,187). Test information along with
      health data including medical diagnoses at time of conscription was available
      through the Swedish Military Conscription Register and the National Patient
      Register. The cohort was followed through linkages to the Swedish Cancer Register
      to identify the occurrence of prostate cancer until December 31, 2009. We used
      Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence
      intervals (95% CI) for the association between acne in adolescence and prostate
      cancer risk. A total of 1,633 men were diagnosed with prostate cancer during a
      median follow-up of 36.7 years. A diagnosis of acne was associated with a
      statistically significant increased risk for prostate cancer (adjusted HR: 1.43
      95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI
      1.19-4.73). A diagnosis of acne classified as severe conferred a sixfold
      increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this
      large prospective population-based cohort add new evidence supporting a role of
      P. acnes infection in prostate cancer.

PMID- 29205340
TI  - Marital Expectations in Strong African American Marriages.
AB  - The current exploratory study utilized a family strengths framework to identify
      marital expectations in 39 strong African American heterosexual marriages.
      Couples reflected on their marital expectations over their 10 or more years of
      marriage. Three themes emerged through qualitative analysis and the participants'
      own words were used in the presentation of the themes. African Americans
      indicated that there was growth in marital expectations over time, with marital
      expectations often beginning with unrealistic expectations that grew into more
      realistic expectations as their marriages progressed. Participants also indicated
      that core expectations in strong African American marriages included open
      communication, congruent values, and positive treatment of spouse. Finally,
      participants explained there is an "I" in marriage as they discussed the
      importance of autonomy within their marital relationships. Results are discussed
      in association with existing research and theory.

PMID- 29205341
TI  - Editorial: The Multidisciplinary World of Couple and Family Therapy and Family
      Science.

PMID- 29205342
TI  - Phylogenetic analyses of the hepatic architecture in vertebrates.
AB  - The mammalian liver has a structural and functional unit called the liver lobule,
      in the periphery of which the portal triad consisting of the portal vein, bile
      duct and hepatic artery is developed. This type of hepatic architecture is
      detectable in many other vertebrates, including amphibians and birds, whereas
      intrahepatic bile ducts run independently of portal vein distribution in
      actinopterygians such as the salmon and tilapia. It remains to be clarified how
      the hepatic architectures are phylogenetically developed among vertebrates. The
      present study morphologically and immunohistochemically analyzed the hepatic
      structures of various vertebrates, including as many classes and subclasses as
      possible, with reference to intrahepatic bile duct distribution. The livers of
      vertebrates belonging to the Agnatha, Chondrichthyes, Amphibia, Aves, Mammalia,
      and Actinopterygii before Elopomorpha, had the portal triad-type architecture.
      The Anguilliformes livers developed both periportal bile ducts and non-periportal
      bile ducts. The Otocephala and Euteleostei livers had independent configuration
      of bile ducts and portal veins. Pancreatic tissues penetrated the liver
      parenchyma along portal veins in the Euteleostei. The liver of the lungfish,
      which shares the same origin with amphibians, did not have the portal triad-type
      architecture. Teleostei and lungfish livers had ductular development in the liver
      parenchyma similar to oval cell proliferation in injured mammalian livers.
      Euteleostei livers had penetration of significant numbers of independent portal
      veins from their intestines, suggesting that each liver lobe might receive a
      different blood supply. The hepatic architectures of the portal triad-type
      changed to non-portal triad-type architecture along the evolution of the
      Actinopterygii. The hepatic architecture of the lungfish resembles that of the
      Actinopterygii after Elopomorpha in intrahepatic biliary configuration, which may
      be an example of convergent evolution.

PMID- 29205343
TI  - Honest, Open, Proud for adolescents with mental illness: pilot randomized
      controlled trial.
AB  - BACKGROUND: Due to public stigma or self-stigma and shame, many adolescents with
      mental illness (MI) struggle with the decision whether to disclose their MI to
      others. Both disclosure and nondisclosure are associated with risks and benefits.
      Honest, Open, Proud (HOP) is a peer-led group program that supports participants
      with disclosure decisions in order to reduce stigma's impact. Previously, HOP had
      only been evaluated among adults with MI. METHODS: This two-arm pilot randomized
      controlled trial included 98 adolescents with MI. Participants were randomly
      assigned to HOP and treatment as usual (TAU) or to TAU alone. Outcomes were
      assessed pre (T0/baseline), post (T1/after the HOP program), and at 3-week follow
      up (T2/6 weeks after T0). Primary endpoints were stigma stress at T1 and quality
      of life at T2. Secondary outcomes included self-stigma, disclosure-related
      distress, empowerment, help-seeking intentions, recovery, and depressive
      symptoms. The trial is registered on ClinicalTrials (NCT02751229;
      http://www.clinicaltrials.gov). RESULTS: Compared to TAU, adolescents in the HOP
      program showed significantly reduced stigma stress at T1 (d = .92, p < .001) and
      increased quality of life at T2 (d = .60, p = .004). In a longitudinal mediation
      model, the latter effect was fully mediated by stigma stress reduction at T1. HOP
      further showed significant positive effects on self-stigma, disclosure-related
      distress, secrecy, help-seeking intentions, attitudes to disclosure, recovery,
      and depressive symptoms. Effects at T1 remained stable or improved further at
      follow-up. In a limited economic evaluation HOP was cost-efficient in relation to
      gains in quality of life. CONCLUSIONS: As HOP is a compact three-session program
      and showed positive effects on stigma and disclosure variables as well as on
      symptoms and quality of life, it could help to reduce stigma's negative impact
      among adolescents with MI.

PMID- 29205344
TI  - Synergistic actions of vitamin D and metformin on skeletal muscles and insulin
      resistance of type 2 diabetic rats.
AB  - Diabetes Mellitus is a chronic generalized disorder due to insulin insufficiency
      or resistance. Skeletal muscles represent one of the most important target organs
      that is affected by insulin signaling. The aim of the current work was to
      investigate the effect of metformin versus vitamin D (and also simultaneous
      administration) therapy in type 2 diabetic (T2D) rats on the state of the muscle
      and insulin sensitivity. Thirty six male rats constituted the animal model and
      have been divided into five groups: control, Diabetic, Diabetic + Metformin,
      Diabetic + Vitamin D, Diabetic + Metformin + Vitamin D. Blood samples were taken
      for biochemical measurements of serum calcium, interleukin-6 (IL-6),
      Triglycerides (TG), glucose, insulin, and calculation of HOMA-IR, and then rats
      were sacrificed, dissected for removal of gastrocnemius muscle that is used for
      both biochemical, histopathological and electron microscopy examination. Oral
      administration of vitamin D alone or in combination with metformin improved
      insulin sensitivity in skeletal muscles, and sustained the metabolic
      complications along with muscle atrophy and inflammation in T2D rats. We
      demonstrated super-beneficial action on insulin resistance of additional vitamin
      D therapy in T2DM rats that were insufficiently controlled by metformin alone.

PMID- 29205345
TI  - Evidence-Based Medicine and State Health Care Coverage: The Washington Health
      Technology Assessment Program.
AB  - OBJECTIVE: To evaluate the Washington State Health Technology Assessment Program
      (WHTAP). STUDY SETTING: Washington State Health Technology Assessment Program
      proceedings in Seattle, Washington. DATA COLLECTION AND STUDY DESIGN: We assessed
      the program through observation of its proceedings over a 5-year period, 2009
      2014. We conducted detailed analyses of the documents it produced and reviewed
      relevant literature. PRINCIPAL FINDINGS: Washington State Health Technology
      Assessment Program is unique compared to other state and federal programs. It has
      successfully applied evidence-based medicine to health care decision making,
      limited by the strength of available data. It claims cost savings, but they are
      not substantiated. CONCLUSIONS: Washington State Health Technology Assessment
      Program is a useful model for other states considering implementation of
      technology assessment programs. We provide key lessons for improving WHTAP's
      process.

PMID- 29205346
TI  - Effect of disease-modifying anti-rheumatic drugs on therapeutic outcomes among
      women with endometriosis.
AB  - OBJECTIVE: To determine whether disease-modifying anti-rheumatic drugs (DMARDs)
      affect the use of hormonal treatments, subsequent ablative surgery, and need for
      pain management, including opioids, non-steroidal anti-inflammatory drugs and
      anti-depressants, among women with endometriosis. METHODS: In a retrospective
      study, data were reviewed from women with surgically confirmed endometriosis who
      were not treated (n=234) or treated with DMARDs for 6 weeks or more (n=25) before
      surgical diagnosis at a single healthcare system in the USA between 2003 and
      2013. The postoperative use of hormonal treatments, proportion of women
      undergoing subsequent ablative surgery, and use of adjunct therapies such as
      antidepressants, steroids, and opioids after surgery were compared between the
      two groups. RESULTS: The two groups showed differences in age (P=0.007) and
      follow-up time (P<0.001). Univariate analysis showed more frequent use of
      hormonal treatments (P=0.045) and antidepressants (P=0.006) among women treated
      with DMARDs. The frequency of post-diagnostic use of opioids was lower among
      treated women (P=0.001); this association remained significant in multivariate
      analysis controlling for potential confounders (P=0.003). CONCLUSION: The
      findings suggest that administration of DMARDs for at least 6 weeks is associated
      with decreased opioid usage among women with endometriosis.

PMID- 29205347
TI  - Low mtDNA variation and shallow population structure of the Chinese pomfret
      Pampus chinensis along the China coast.
AB  - In the present study, population genetic structure and genetic diversity of the
      Chinese pomfret Pampus chinensis, along the China coast were investigated and
      compared with that from Indonesia using mitochondrial DNA cytochrome b gene
      sequences. A total of 28 variable sites (including 18 singleton sites and 10
      parsimony information sites) were observed and 23 haplotypes were defined in 330
      individuals from 11 localities. The haplotype diversity (HD ) of the populations
      ranged from 0.540 to 0.828, the nucleotide diversity (pi) ranged from 0.081 to
      0.295%. Pairwise FST statistics showed that significant genetic divergence
      occurred among populations from different geographical regions. The high
      dispersal capabilities, geographic segregation and ocean currents may be
      responsible for the present population genetic structure in this species. In
      addition, a population expansion event during the late Pleistocene period was
      inferred. The time of population expansion was estimated to occur about 117 000
      169 000 years ago.

PMID- 29205348
TI  - Exploring the Potential of Mesquite Gum-Nopal Mucilage Mixtures: Physicochemical
      and Functional Properties.
AB  - : In this work the physicochemical and functional properties of mesquite gum (MG)
      and nopal mucilage (NM) mixtures (75-25, 50-50, 25-75) were evaluated and
      compared with those of the individual biopolymers. MG-NM mixtures exhibited more
      negative zeta potential (ZP) values than those displayed by MG and NM, with 75-25
      MG-NM showing the most negative value (-14.92 mV at pH = 7.0), indicative that
      this biopolymer mixture had the highest electrostatic stability in aqueous
      dispersions. Viscosity curves and strain amplitude sweep of aqueous dispersions
      (30% w/w) of the individual gums and their mixtures revealed that all exhibited
      shear thinning behavior, with NM having higher viscosity than MG, and all
      displaying fluid-like viscoelastic behavior where the loss modulus predominated
      over the storage modulus (G">G'). Differential Scanning Calorimetry revealed that
      MG, NM, and MG-NM mixtures were thermally stable with decomposition peaks in a
      range from 303.1 to 319.6  degrees C. From the functional properties viewpoint,
      MG (98.4 +/- 0.7%) had better emulsifying capacity than NM (51.9 +/- 2.0%), while
      NM (43.0 +/- 1.4%) had better foaming capacity than MG. MG-NM mixtures acquired
      additional functional properties (emulsifying and foaming) regarding the
      individual biopolymers. Therefore, MG-NM mixtures represent interesting
      alternatives for their application as emulsifying and foaming agents in food
      formulations. PRACTICAL APPLICATION: Mesquite gum (MG) and nopal mucilage (NM)
      are promising raw materials with excellent functional properties whose use has
      been largely neglected by the food industry. This work demonstrates MG-NM
      mixtures acquired additional functional properties regarding the individual
      biopolymers, making these mixtures multifunctional ingredients for the food
      industry.

PMID- 29205349
TI  - Perioperative cytokine levels portend early death after pancreatectomy for ductal
      adenocarcinoma.
AB  - BACKGROUND: Soluble signaling molecules may play an important role in malignant
      pathogenesis. We hypothesize that perioperative cytokine levels are associated
      with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing
      surgical resection. METHODS: One hundered and eighteen patients with benign or
      malignant pancreatic disease were enrolled in a prospective study through a
      protocol for banking biologic samples. Peripheral blood was drawn at time of
      operation, and a multiplex cytokine assay was performed. Statistical analysis was
      via chi2 and Kaplan Meier methods. RESULTS: Of 118 patients enrolled, 85 (72%)
      had a diagnosis of PDAC, and 60 (70%) ultimately underwent partial
      pancreatectomy. Cytokine levels were not associated with postoperative
      complications in this initial cohort. A plasma level of monocyte chemoattractant
      protein-1 (MCP-1) pg/mL <=118 was associated with better overall survival (OS)
      (median survival 21 months vs 12.8 months, P = 0.023), as was non-detectable
      interleukin-8 (IL-8) (19 months) versus detectable IL-8 (12.8 months, P = 0.05).
      Patients with both MCP-1 >118 pg/mL and detectable IL-8 had a median survival of
      10.6 months (P = 0.028). CONCLUSIONS: MCP-1 and IL-8 cytokine levels are
      associated with decreased survival following pancreatectomy for PDAC, and may be
      useful biomarkers. Measurement of these cytokine levels at different time points
      in future investigations will be important to validate these findings.

PMID- 29205350
TI  - A more sensitive detection of micrometastases of NSCLC in lymph nodes using the
      one-step nucleic acid amplification (OSNA) method.
AB  - BACKGROUND: Detection of tumor cells in lymph nodes (LNs) removed during the
      treatment of pulmonary tumor by radical surgery is limited by the possibilities
      of standard histopathological methods. The goal of this study was to obtain more
      accurate pTNM status by a more sensitive detection of micrometastases in LNs.
      METHODS: A total of 885 LNs, an average of 13.8 LNs per patient, were removed
      during 64 surgeries. LNs from the same zone were pooled together as a group, five
      groups of LNs were examined in each patient. A total of 320 groups of LNs were
      examined. One-step nucleic acid amplification (OSNA) method was compared to
      standard histopathological examination with haematoxylin-eosin (H&E) staining and
      CK19 immunohistochemistry, specifically by an ultimate analysis of all
      intraoperatively removed LNs. RESULTS: Identical results for H&E and OSNA
      examinations were recorded in 286 groups of LNs (89.4%). In total, positive
      examinations were recorded in 27 groups of LNs (8.4%) using the OSNA method,
      which were H&E negative. In seven groups of LNs (2.2%), the H&E examination was
      positive, while OSNA method produced negative results. CONCLUSIONS: The OSNA
      examination led to a higher pTNM stage classification in 14 (21.9%) patients. The
      clinical significance remains the subject of follow-up research.

PMID- 29205353
TI  - Subconjunctival Dirofilaria repens infection in a dog resident in the UK.
AB  - Dirofilaria repens infection was diagnosed in a 5-year-old female German shepherd
      crossbreed, originally from Romania but brought into the UK in February 2014. The
      dog presented with conjunctivitis in March 2014 and then again 2 months later
      with additional ocular and nasal mucopurulent discharge. Bacterial cultures from
      the nasolacrimal duct were negative for bacterial growth. The case was referred
      in August 2014 for ophthalmic examination, which revealed abnormalities in both
      eyes, especially the left. They included mild palpebral conjunctival hyperaemia
      and marked follicular conjunctivitis, as well as a dorsonasal bulbar conjunctival
      mass. Serum biochemistry was unremarkable and a conjunctival biopsy taken from
      the dorsonasal bulbar conjunctival mass revealed eosinophilic/lymphoplasmacytic
      conjunctivitis. At re-examination, nematodes were found in the area of the
      previous biopsy site and in the ventral palpebral conjunctival fornix. Polymerase
      chain reaction and sequencing confirmed these to be D. repens. Treatment with 10%
      imidacloprid and 2.5% moxidectin (Advocate Spot-On) was successful, and clinical
      signs resolved over a 6-week period. This case report indicates that D. repens
      infection should be considered as a possible aetiological cause of ocular lesions
      in dogs in the UK, especially those with a history of foreign travel.
      Implications for establishment and spread of D. repens in the UK are discussed.

PMID- 29205352
TI  - Characteristics and long-term survival of patients diagnosed with pure tubular
      carcinoma of the breast.
AB  - BACKGROUND AND OBJECTIVES: Pure tubular carcinomas (TC) of the breast are
      generally considered to have an excellent prognosis. This study aimed to analyze
      the characteristics and survival of patients with TC. METHODS: This was a
      retrospective study conducted at the CHU de Quebec-Universite Laval. Databases
      were searched for all cases treated between April 1997 and December 2010.
      Survival was retrieved from the Province of Quebec Ministry of Health. Follow-up
      was censored on December 31, 2011. Overall survival (OS) was compared to patients
      with invasive ductal carcinoma (ICD) matched for age, tumor size, lymph node
      involvement, year of diagnosis, ER, PgR, and HER2, histological grade,
      lymphovascular invasion, and chemotherapy. RESULTS: The frequency of TC was 2.9%
      (n = 223/7563). Tumors size was 7.4 +/- 8.8 mm, without lymphovascular invasion
      (95.1%), ER-positive (98.2%), PgR-positive (69.5%), and HER2-negative (100%).
      Patients were followed up for 7.1 +/- 2.7 years. The actuarial 13-year OS was
      89.0% for TC, compared to 85.8% for IDC (P = 0.13). For TC, the 13-year OS was
      95.8% in NO patients compared to 90.0% for N1-3 (P = 0.01). CONCLUSION: Despite
      the general popular belief that patients with TC fare better than patients with
      IDC, the 13-year OS of TC was similar to that of grade I IDC.

PMID- 29205351
TI  - Oncologic effects of preoperative biliary drainage in resectable hilar
      cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on
      survival.
AB  - BACKGROUND AND OBJECTIVES: The objective of the current study was to define long
      term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after
      preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic
      biliary drainage (EBD). METHODS: Between 2000 and 2014, 240 patients who
      underwent curative-intent resection for HCCA were identified at 10 major
      hepatobiliary centers. Postoperative morbidity and mortality, as well as disease
      specific survival (DSS) and recurrence-free survival (RFS) were analyzed among
      patients. RESULTS: The median decrease in total bilirubin levels after biliary
      drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs
      4.9, P = 0.589) before surgery. There was no difference in baseline demographic
      characteristics, type of surgical procedure performed, final AJCC tumor stage or
      postoperative morbidity among patients who underwent EBD only versus PTBD (all P
      > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS
      (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P
      = 0.571). The overall pattern of recurrence relative to regional or distant
      disease was also the same among patients undergoing PTBD and EBD (P = 0.669)
      CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients
      who underwent PTBD versus EBD with no difference in tumor recurrence location.

PMID- 29205354
TI  - Podocytes are new cellular targets of haemoglobin-mediated renal damage.
AB  - Recurrent and massive intravascular haemolysis induces proteinuria,
      glomerulosclerosis, and progressive impairment of renal function, suggesting
      podocyte injury. However, the effects of haemoglobin (Hb) on podocytes remain
      unexplored. Our results show that cultured human podocytes or podocytes isolated
      from murine glomeruli bound and endocytosed Hb through the megalin-cubilin
      receptor system, thus resulting in increased intracellular Hb catabolism,
      oxidative stress, activation of the intrinsic apoptosis pathway, and altered
      podocyte morphology, with decreased expression of the slit diaphragm proteins
      nephrin and synaptopodin. Hb uptake activated nuclear factor erythroid-2-related
      factor 2 (Nrf2) and induced expression of the Nrf2-related antioxidant proteins
      haem oxygenase-1 (HO-1) and ferritin. Nrf2 activation and Hb staining was
      observed in podocytes of mice with intravascular haemolysis. These mice developed
      proteinuria and showed podocyte injury, characterized by foot process effacement,
      decreased synaptopodin and nephrin expression, and podocyte apoptosis. These
      pathological effects were enhanced in Nrf2-deficient mice, whereas Nrf2
      activation with sulphoraphane protected podocytes against Hb toxicity both in
      vivo and in vitro. Supporting the translational significance of our findings, we
      observed podocyte damage and podocytes stained for Hb, HO-1, ferritin and
      phosphorylated Nrf2 in renal sections and urinary sediments of patients with
      massive intravascular haemolysis, such as atypical haemolytic uraemic syndrome
      and paroxysmal nocturnal haemoglobinuria. In conclusion, podocytes take up Hb
      both in vitro and during intravascular haemolysis, promoting oxidative stress,
      podocyte dysfunction, and apoptosis. Nrf2 may be a potential therapeutic target
      to prevent loss of renal function in patients with intravascular haemolysis.
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29205355
TI  - Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique
      challenges.
AB  - BACKGROUND: Breast angiosarcoma (AS) accounts for less than 1% of all breast
      cancers. The goal of this study was to determine patient outcomes in radiation
      associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated
      patterns of recurrence and predictors of breast AS survival. METHODS: Patients
      with pathologically confirmed AS from 1994 to 2014 referred to Mount Sinai
      Hospital/Princess Margaret Cancer Centre were included. Primary outcome was
      overall survival (OS). Secondary outcomes were disease-free survival (DFS),
      clinicopathologic characteristics, patterns of recurrence and factors predictive
      of survival. Kaplan-Meier and log-rank tests were used for OS and DFS. RESULTS:
      Twenty-six patients were included: 6 with sporadic AS and 20 with RAAS. Median
      follow-up was 24 months. Five-year OS for RAAS and sporadic subgroups were 44%
      and 40%, respectively (P = ns). Five-year DFS for RAAS and sporadic subgroups
      were 23% and 20%, respectively (P = ns). Overall recurrence rate was 67% with
      median time to recurrence of 11 months. Age, tumor depth, margin status, and
      tumor size were not statistically significant predictive factors for OS and DFS.
      DISCUSSION: Breast AS is associated with poor survival and high recurrence rates.
      Prognosis may be mainly determined by its aggressive biology. Referral to
      tertiary care centers for multimodality treatment is recommended.

PMID- 29205357
TI  - Hexokinase 2-dependent hyperglycolysis driving microglial activation contributes
      to ischemic brain injury.
AB  - Hyperglycolysis, observed within the penumbra zone during brain ischemia, was
      shown to be detrimental for tissue survival because of lactate accumulation and
      reactive oxygen species overproduction in clinical and experimental settings.
      Recently, mounting evidence suggests that glycolytic reprogramming and induced
      metabolic enzymes can fuel the activation of peripheral immune cells. However,
      the possible roles and details regarding hyperglycolysis in neuroinflammation
      during ischemia are relatively poorly understood. Here, we investigated whether
      overactivated glycolysis could activate microglia and identified the crucial
      regulators of neuroinflammatory responses in vitro and in vivo. Using BV 2 and
      primary microglial cultures, we found hyperglycolysis and induction of the key
      glycolytic enzyme hexokinase 2 (HK2) were essential for microglia-mediated
      neuroinflammation under hypoxia. Mechanistically, HK2 up-regulation led to
      accumulated acetyl-coenzyme A, which accounted for the subsequent histone
      acetylation and transcriptional activation of interleukin (IL)-1beta. The
      inhibition and selective knockdown of HK2 in vivo significantly protected against
      ischemic brain injury by suppressing microglial activation and IL-1beta
      production in male Sprague-Dawley rats subjected to transient middle cerebral
      artery occlusion (MCAo) surgery. We provide novel insights for HK2 specifically
      serving as a neuroinflammatory determinant, thus explaining the neurotoxic effect
      of hyperglycolysis and indicating the possibility of selectively targeting HK2 as
      a therapeutic strategy in acute ischemic stroke.

PMID- 29205356
TI  - Molecular and functional characterization of inwardly rectifying K+ currents in
      murine proximal colon.
AB  - KEY POINTS: Interstitial cells of Cajal (ICC) from murine colonic muscles express
      genes encoding inwardly rectifying K+ channels. Transcripts of Kcnj2 (Kir2.1),
      Kcnj4 (Kir2.3), Kcnj14 (Kir2.4), Kcnj5 (Kir3.4), Kcnj8 (Kir 6.1) and Kcnj11
      (Kir6.2) were found in colonic ICC. A conductance with properties consistent with
      Kir2 channels was observed in ICC but not in smooth muscle cells (SMC). Despite
      expression of gene transcripts, G-protein gated K+ channel (Kir3) and KATP (Kir6)
      currents were not resolved in ICC. KATP is a conductance prominent in SMC. Kir2
      antagonist caused depolarization of freshly dispersed ICC and colonic smooth
      muscles, suggesting that this conductance is active under resting conditions in
      colonic muscles. The conclusion of the present study is that ICC express the Ba2+
      -sensitive, inwardly rectifying K+ conductance in colonic muscles. This
      conductance is most probably a result of heterotetramers of Kir2 gene products,
      with this regulating resting potentials and the excitability of colonic muscles.
      ABSTRACT: Membrane potentials of gastrointestinal muscles are important because
      voltage-dependent Ca2+ channels in smooth muscle cells (SMC) provide the Ca2+
      that triggers contraction. Regulation of membrane potential is complicated
      because SMC are electrically coupled to interstitial cells of Cajal (ICC) and
      PDGFRalpha+ cells. Activation of conductances in any of these cells affects the
      excitability of the syncytium. We explored the role of inward rectifier K+
      conductances in colonic ICC that might contribute to regulation of membrane
      potential. ICC expressed Kcnj2 (Kir2.1), Kcnj4 (Kir2.3), Kcnj14 (Kir2.4), Kcnj5
      (Kir3.4), Kcnj8 (Kir 6.1) and Kcnj11 (Kir6.2). Voltage clamp experiments showed
      activation of inward current when extracellular K+ ([K+ ]o ) was increased. The
      current was inwardly rectifying and inhibited by Ba2+ (10 MUm) and ML-133 (10
      MUm). A similar current was not available in SMC. The current activated in ICC by
      elevated [K+ ]o was not affected by Tertiapin-Q. Gbetagamma, when dialysed into
      cells, failed to activate a unique, Tertiapin-Q-sensitive conductance. Freshly
      dispersed ICC showed no evidence of functional KATP . Pinacidil failed to
      activate current and the inward current activated by elevated [K+ ]o was
      insensitive to glibenclamide. Under current clamp, ML-133 caused the
      depolarization of isolated ICC and also that of cells impaled with
      microelectrodes in intact muscle strips. These findings show that ICC, when
      isolated freshly from colonic muscles, expressed a Ba2+ -sensitive, inwardly
      rectifying K+ conductance. This conductance is most probably a result of the
      expression of multiple Kir2 family paralogues, and the inwardly rectifying
      conductance contributes to the regulation of resting potentials and excitability
      of colonic muscles.

PMID- 29205358
TI  - Prognostic impact of postoperative pulmonary complications following salvage
      esophagectomy after definitive chemoradiotherapy.
AB  - BACKGROUND: Postoperative complications after esophagectomy for esophageal cancer
      have a negative effect on patients' survival. Although postoperative
      complications are more frequently observed after salvage esophagectomy than after
      planned esophagectomy, the effects of postoperative complications on long-term
      oncologic outcomes after salvage esophagectomy remain unclear. METHODS: This
      retrospective study of 70 esophageal cancer patients after definitive
      chemoradiotherapy (dCRT) compared long-term outcomes between those with and
      without complications. The association between morbidity and overall survival
      (OS) was evaluated by a Cox regression analysis. To identify the risk factors for
      pulmonary complications, logistic regression analysis was carried out. RESULTS:
      Postoperative complications occurred in 42 (60.0%) patients. Pulmonary
      complications and anastomotic leakage occurred in 23 (32.9%) and 9 (12.9%)
      patients, respectively. Overall complications and anastomotic leakage did not
      affect long-term outcomes. Survival was significantly worse for patients with
      pulmonary complications. Radiation dose (<60 Gy), response to dCRT (complete),
      ypStage (0-II), residual disease (R0), and pulmonary complications (negative)
      were independent factors related to a favorable OS. BMI (<20 kg/m2 ), ASA-PS (2
      3), and radiation dose (>60 Gy) were significant factors affecting the occurrence
      of pulmonary complications. CONCLUSIONS: Development of postoperative pulmonary
      complications was independently associated with poor prognosis in patients who
      underwent salvage esophagectomy after dCRT.

PMID- 29205359
TI  - Effects of estrogen replacement therapy on the myelin sheath ultrastructure of
      myelinated fibers in the white matter of middle-aged ovariectomized rats.
AB  - The effects of estrogen replacement therapy (ORT) on white matter and the myelin
      sheath ultrastructure in the white matter of middle-aged ovariectomized (OVX)
      rats were investigated in this study. Middle-aged rats were ovariectomized and
      divided into a placebo replacement (OVX + O) group and an estrogen replacement
      (OVX + E) group. Then, the Morris water maze, electron microscope techniques, and
      stereological methods were used to investigate the effects of ORT on spatial
      learning capacity, white matter volume and the myelin sheath ultrastructure in
      the white matter. We found that the spatial learning capacity of the OVX + E rats
      was significantly improved compared with that of the OVX + O rats. When compared
      with that of OVX + O rats, the total volume of the myelin sheaths in the white
      matter of the OVX + E rats was significantly increased by 27%, and the difference
      between the outer perimeter and inner perimeter of the myelin sheaths of the
      white matter in the OVX + E rats increased significantly by 12.6%. The myelinated
      fibers with mean diameters of 1.2-1.4 MUm were significantly longer (46.1%) in
      the OVX + E rats; the difference between the mean diameter of myelinated fibers
      and the mean diameter of axons (0-0.4 MUm) was significantly increased by 21.6%
      in the OVX + E rats. These results suggested that ORT had positive protective
      effects on the spatial learning ability and on the myelin sheath ultrastructure
      in the white matter of middle-aged OVX rats.

PMID- 29205360
TI  - Chemical marking of European glass eels Anguilla anguilla with alizarin red S and
      in combination with strontium: in situ evaluation of short-term salinity effects
      on survival and efficient mass-marking.
AB  - This study presents a new chemical double-marking technique for European glass
      eels Anguilla anguilla by combing alizarin red S (ARS) and strontium chloride
      hexahydrate (Sr). Marked eels (double marked with ARS and Sr, but also single
      marked with ARS) were exposed in situ to brackish water (15 g l-1 artificial sea
      salt) for 14 days and did not exhibit increased mortalities compared with
      unmarked eels. Indeed, no mortality occurred in a marked group during the
      experiments. Moreover, an efficient mass-marking approach with low handling
      effort for both single ARS and double ARS-Sr techniques is described and was
      proven to be practicable for large-scale stocking programmes.

PMID- 29205361
TI  - Vascular anatomy of the jejunal mesentery and complications associated with
      division of the first jejunal venous trunk during pancreaticoduodenectomy.
AB  - BACKGROUND: Little is known about the anatomy of the jejunal veins (JVs) flowing
      into the superior mesenteric vein (SMV), and whether they can be safely divided
      during pancreaticoduodenectomy. METHODS: Computed tomography was used to review
      the jejunal branches off the superior mesenteric artery (SMA) and into the SMV in
      123 consecutive patients. The common trunk of the JVs (jejunal venous trunk, JVT)
      was classified as ventral or dorsal to the SMA. RESULTS: The first JVT involved
      multiple JVs in 108 (87.8%) cases. The first JVT diameter (>=7 or <7 mm) was
      significantly associated with the number of JVs (>=4 or <4; P < 0.05). Surgical
      outcomes were not significantly different between cases in which the first JVT
      was sacrificed (n = 32) or preserved (n = 91), except for operation time and
      portal venous resection frequency. One of the 32 cases (3.1%) with first JVT
      sacrifice showed severe congestion of the jejunal limb requiring emergency
      jejunal resection. CONCLUSIONS: The size and topology of the first JVT are
      associated with the number of JVs involved. This is important for understanding
      the resectional area of the mesojejunum and the pathogenesis of jejunal
      congestion.

PMID- 29205362
TI  - Anti-oncostatin M antibody inhibits the pro-malignant effects of oncostatin M
      receptor overexpression in squamous cell carcinoma.
AB  - The oncostatin M (OSM) receptor (OSMR) shows frequent gene copy number gains and
      overexpression in cervical squamous cell carcinomas (SCCs), associated with
      adverse clinical outcomes. In SCC cells that overexpress OSMR, the major ligand
      OSM induces multiple pro-malignant effects, including invasion, secretion of
      angiogenic factors, and metastasis. Here, we demonstrate, for the first time,
      that OSMR overexpression in SCC cells activates cell-autonomous feed-forward
      signalling, via further expression of OSMR and OSM and sustained STAT3
      activation, despite expression of the negative regulator suppressor of cytokine
      signalling 3 (SOCS3). The pro-malignant effects associated with OSMR
      overexpression are critically mediated by JAK-STAT3 activation, which is induced
      by exogenous OSM and also by autocrine OSM-OSMR interactions. Importantly,
      specific inhibition of OSM-OSMR interactions by neutralizing antibodies
      significantly inhibits STAT3 activation and feed-forward signalling, leading to
      reduced invasion, angiogenesis, and metastasis. Our findings are supported by
      data from 1254 clinical SCC samples, in which OSMR levels correlated with
      multiple cognate genes, including OSM, STAT3, and downstream targets. These data
      strongly support the development of OSM-OSMR-blocking antibodies as biologically
      targeted therapies against SCCs of the cervix and other anatomical sites.
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29205363
TI  - Risk of peritoneal metastases in patients who had negative peritoneal staging and
      received therapy for localized gastric adenocarcinoma.
AB  - BACKGROUND: Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC)
      carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended
      for all >=T1b gastric adenocarcinoma (GAC). The natural history of patients with
      GAC who have baseline -PCyt and then undergo multimodality therapy is not well
      documented, particularly for the risk of subsequent GPC. METHODS: We identified
      238 GAC patients with baseline -PCyt who were followed for the development of
      peritoneal carcinomatosis (PC). Standard statistical methods were employed.
      RESULTS: Of 238 patients, 192 had attempted surgery after preoperative therapy.
      Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery
      was aborted. We followed 164 patients who had an R0 resection. The median follow
      up duration was 3.4 (range, 0.6-18) years. The rate of PC was 13.4%, (22/164
      patients) and the median time to PC was 15.6 months. Female gender was associated
      with PC on multivariate analysis. The 5-year OS rate for patients without
      subsequent PC was 75%. Conclusion Even with baseline -Cyt, ~25% of patients
      develop PC following multimodality therapy. Patients who do not develop PC have
      an excellent OS rate. Further research is warranted to detect PC at baseline by
      the use of biomarkers.

PMID- 29205364
TI  - Effects of local multivisceral resection for clinically locally advanced rectal
      cancer on long-term outcomes.
AB  - INTRODUCTION: Multivisceral resection is occasionally needed to obtain clear
      margins in patients with transmural rectal cancer. Most series demonstrate
      equivalent outcomes between those patients who undergo multivisceral resections
      and those who do not, provided an R0-resection is achieved. This study focuses
      solely on patients who received neoadjuvant treatment for clinically transmural
      rectal cancers and underwent a local multivisceral R0-resection. METHODS: A
      retrospective, single center analysis of consecutive series of patients who
      received a surgical R0-resection after neoadjuvant treatment for a clinically
      transmural, non-metastatic, primary rectal cancer. All patients were operated on
      between 2004 and 2015. RESULTS: A total of 279 patients was included, of whom 29
      patients underwent a local multivisceral R0-resection (LMVR). These patients were
      more often female and less often diagnosed through screening. Pathologic AJCC
      staging was significantly lower for non-LMVR patients, with more favorable tumor
      characteristics. LMVR patients demonstrated higher rates of distant disease
      recurrence, and impaired survival, even after adjusting for disease stage.
      CONCLUSION: An R0-resection after neoadjuvant therapy led to comparative local
      control of disease; however, patients with multivisceral resection had more
      distant recurrence and impaired survival, compared to those did not undergo a
      multivisceral resection. Further research should determine optimal postoperative
      care.

PMID- 29205365
TI  - Taking intestinal anion secretion to TASK: a role for K2P channels in cyclic AMP
      regulated anion secretion.

PMID- 29205366
TI  - Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness
      analysis.
AB  - BACKGROUND AND OBJECTIVES: Accurate preoperative staging helps avert morbidity,
      mortality, and cost associated with non-therapeutic laparotomy in gastric cancer
      (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with
      high sensitivity, but its cost-effectiveness has not been previously studied. We
      developed a decision analysis model to assess the cost-effectiveness of
      preoperative DSL in GC workup. METHODS: Analysis was based on a hypothetical
      cohort of GC patients in the U.S. for whom initial imaging shows no metastases.
      The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year
      (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity
      analysis. RESULTS: Preoperative DSL required an investment of $107 012 per QALY.
      In sensitivity analysis, DSL became cost-effective at a threshold of $100
      000/QALY when the probability of occult metastases exceeded 31.5% or when test
      sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness
      increased from 46% to 93% when both parameters were set at maximum reported
      values. CONCLUSIONS: The cost-effectiveness of DSL for GC patients is highly
      dependent on patient and test characteristics, and is more likely when DSL is
      used selectively where procedure yield is high, such as for locally advanced
      disease or in detecting peritoneal and superficial versus deep liver lesions.

PMID- 29205368
TI  - Cyclic AMP-dependent protein kinase catalytic subunit A (PRKACA): the expected,
      the unexpected, and what might be next.
AB  - Protein kinase A (PKA) or cyclic-AMP (cAMP)-dependent kinase was among the first
      serine-threonine kinases to be molecularly and functionally characterized. For
      years, it was investigated as the enzyme that mediates cAMP functions in almost
      all cell systems and organisms studied to date. Despite PKA's critical role in
      signaling and the long history of investigations of cAMP in oncogenesis (dating
      back to the 1970s), it was not until relatively recently that PKA defects were
      found to be directly involved in tumor predisposition. First, PKA's main
      regulatory subunit, PRKAR1A, was found to be mutated in Carney complex, a genetic
      syndrome that predisposes to heart tumors (cardiac myxomas) and a variety of
      other lesions of the endocrine system, including the adrenal cortex, and several
      cancers, including liver carcinoma. Then, PKA's main catalytic subunit, PRKACA,
      was found to be mutated in sporadic adrenal tumors and fibrolamellar liver
      carcinoma. Not surprisingly, therefore, a new research study published in The
      Journal of Pathology showed PRKACA mutations in sporadic cardiac myxomas. The
      real question is what other pathologies will be found to be due to PRKACA (or
      other PKA subunit) defects. The possibilities abound and may show the way for a
      totally new class of medications that target cAMP signaling to be useful in
      fighting the corresponding tumors. Published 2017. This article is a U.S.
      Government work and is in the public domain in the USA.

PMID- 29205367
TI  - Statistical analysis of wheat under different seed treatments: development of a
      discriminative model based on physicochemical and rheological properties.
AB  - BACKGROUND: Quality control in the wheat industry comprises numerous analyses
      that are time-consuming and demand numerous procedures and specific apparatus.
      The application of multivariate calibration techniques contributes to the
      interpretation of the data generated during these analyses. The present study
      aimed to correlate a representative number of wheat properties with the treatment
      applied to the wheat seeds using multivariate calibration techniques. RESULTS: In
      the present study, a wheat pilot planting experiment applying different
      fungicides combination as a seed treatment (carbendazim, carbendazim + thiram,
      carboxin + thiram, and triadimenol) was conducted. The resulting wheat grains
      were subjected to 33 analyses routinely performed in industry. A principal
      components analysis indicated all analyses were relevant for the different seed
      treatment discrimination. Afterwards, a k-nearest neighbors discriminative model
      was developed and was able to classify the seed treatments. In accordance with
      this model, the most relevant variables for the seed treatment discrimination
      were the rheological properties of the dough. CONCLUSION: It was possible to
      develop a discriminative model that directly correlated the wheat seed treatment
      with the properties of the resulting grains and flours. (c) 2017 Society of
      Chemical Industry.

PMID- 29205370
TI  - Abstracts of the Royal Pharmaceutical Society (RPS) Winter Summit 2017, London,
      UK, 5 December 2017.

PMID- 29205369
TI  - Regulatory B cells induced by ultraviolet B through toll-like receptor 4
      signalling contribute to the suppression of contact hypersensitivity responses in
      mice.
AB  - BACKGROUND: Ultraviolet (UV) B irradiation is known to suppress contact
      hypersensitivity (CHS) responses in mouse models by suppressing immune responses.
      However, the cellular mechanisms responsible for UVB-induced systemic suppression
      remain unclear. Regulatory B cells have been reported to play an inhibitory role
      during CHS. It is presently unknown whether regulatory B cells contribute to the
      effect of UVB phototherapy. OBJECTIVE: To investigate the inductive effect of UVB
      on regulatory B cells and the underlying mechanisms by using a CHS mouse model.
      METHODS: CHS was induced with oxazolone, and evaluated by histopathology, flow
      cytometry, and quantitative real-time polymerase chain reaction. RESULT: We found
      that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. UVB
      induced regulatory B cells contribute to systemic immunosuppression by inhibiting
      the proliferation of T cells. Moreover, we determined that toll-like receptor
      (TLR) 4, the expression of which was upregulated in B cells after UVB exposure,
      played an essential role in the induction of regulatory B cells. CONCLUSION: Our
      data identified regulatory B cells as regulators of UVB-induced immunosuppression
      in CHS, and suggest the importance of the UVB-TLR4 axis in the generation of
      regulatory B cells.

PMID- 29205372
TI  - The falsifiability of Swets' ROC may bring consensus to search performance
      assessment.

PMID- 29205371
TI  - Characterization of the canine rostral ventricular-subventricular zone:
      Morphological, immunohistochemical, ultrastructural, and neurosphere assay
      studies.
AB  - The mammalian ventricular-subventricular zone (V-SVZ) presents the highest
      neurogenic potential in the brain of the adult individual. In rodents, it is
      mainly composed of chains of neuroblasts. In humans, it is organized in layers
      where neuroblasts do not form chains. The aim of this study is to describe the
      cytoarchitecture of canine V-SVZ (cV-SVZ), to assess its neurogenic potential,
      and to compare our results with those previously described in other species. We
      have studied by histology, immunohistochemistry (IHC), electron microscopy and
      neurosphere assay the morphology, cytoarchitecture and neurogenic potential of cV
      SVZ. Age groups of animals were performed. Histological and ultrastructural
      studies indicated that the cV-SVZ is organized in layers as in humans, but
      including migratory chains as in rodents. Neural progenitors were organized in
      niches in the subependymal area and a decline in their number was observed with
      age. Adult-young dogs contained migratory cells capable to expand and
      differentiate in vitro according with previous results obtained in rodents,
      primates, humans, pigs, and dogs. Some adult animals presented perivascular
      niches outside the V-SVZ. Our observations evidence a great similarity between
      canine and human V-SVZ indicating that the dog may be better representative of
      neurogenic events in humans, compared with rodents. Accordingly with our results,
      we conclude that dogs are a valuable animal model of adult neurogenesis in
      comparative and preclinical studies.

PMID- 29205373
TI  - Coexistence via coevolution driven by reduced allelochemical effects and
      increased tolerance to competition between invasive and native plants.
AB  - Coevolution can promote long-term coexistence of two competing species if
      selection acts to reduce the fitness inequality between competitors and/or
      strengthen negative frequency dependence within each population. However, clear
      coevolution between plant competitors has been rarely documented. Plant invasions
      offer opportunities to capture the process of coevolution. Here we investigated
      how the developing relationship between an invasive forb, Alliaria petiolata, and
      a native competitor, Pilea pumila, may affect their long-term coexistence, by
      testing the competitive effects of populations of varying lengths of co
      occurrence on each other across a chronosequence of invasion history. Alliaria
      petiolata and P. pumila tended to develop greater tolerance to competition over
      invasion history. Their coexistence was promoted more by increases in stabilizing
      relative to equalizing processes. These changes likely stem in part from
      reductions in allelopathic traits in the invader and evolution of tolerance in
      the native. These results suggested that some native species can evolve tolerance
      against the competitive effects of strong invaders, which likely promoted their
      persistence in invaded communities. However, the potential for coevolutionary
      rescue of competing populations is likely to vary across native species, and
      evolutionary processes should not be expected to compensate for the ecological
      consequences of exotic invasions.

PMID- 29205374
TI  - Ethyl chloride spray for musculoskeletal ultrasound-guided injections: An
      alternative to subcutaneous injection of local anesthetic solution.
AB  - Ultrasound-guided injections such as steroid injections are common procedures
      involving the musculoskeletal system. They are usually performed after a
      subcutaneous injection of local anesthetic (LA), which can be painful. In 126
      consecutive patients, local anesthesia was performed using ethyl chloride spray
      prior to a therapeutic ultrasound-guided injection in joints, tendons, or bursae.
      Ninety-nine (78.5%) patients found the use of ethyl chloride spray helpful. The
      use of ethyl chloride spray is an effective, patient-friendly alternative to the
      standard injection of local aesthetic for ultrasound-guided therapeutic
      musculoskeletal injections with the advantage of a lower cost of $0.18 per
      procedure.

PMID- 29205375
TI  - Comparison of direct in-house cerebrospinal fluid cytology with commercial
      pathology results in dogs.
AB  - OBJECTIVES: To investigate the correspondence between in-house direct cytological
      assessment of cerebrospinal fluid and results from a commercial veterinary
      pathology laboratory. METHODS: Prospective inclusion of samples from dogs that
      were presented for investigation of suspected neurological disease and had
      cerebrospinal fluid samples submitted to a commercial pathology laboratory for
      analysis. A board-certified veterinary pathologist assessed all cerebrospinal
      fluid samples, and a line smear was assessed in-house by two observers. Nucleated
      cell count, red blood cell count and differential cell counts were recorded and
      compared. RESULTS: In-clinic and commercial pathology nucleated cell counts and
      red blood cell counts were strongly correlated. In-house line smear results were
      compared with the gold standard of a defined dichotomous rating of 'increased
      nucleated cell count' provided by the external pathology service. Sensitivity was
      93% and specificity 80% for samples with at least two cells per linear field.
      CLINICAL APPLICATION: Although not a replacement for the assessment of
      cerebrospinal fluid samples by specialist veterinary pathologists, this method
      can provide rapid and clinically meaningful information before externally
      processed sample results are available.

PMID- 29205376
TI  - Ensemble gene function prediction database reveals genes important for complex I
      formation in Arabidopsis thaliana.
AB  - Recent advances in gene function prediction rely on ensemble approaches that
      integrate results from multiple inference methods to produce superior
      predictions. Yet, these developments remain largely unexplored in plants. We have
      explored and compared two methods to integrate 10 gene co-function networks for
      Arabidopsis thaliana and demonstrate how the integration of these networks
      produces more accurate gene function predictions for a larger fraction of genes
      with unknown function. These predictions were used to identify genes involved in
      mitochondrial complex I formation, and for five of them, we confirmed the
      predictions experimentally. The ensemble predictions are provided as a user
      friendly online database, EnsembleNet. The methods presented here demonstrate
      that ensemble gene function prediction is a powerful method to boost prediction
      performance, whereas the EnsembleNet database provides a cutting-edge community
      tool to guide experimentalists.

PMID- 29205377
TI  - Adenosine A2A receptors are required for glutamate mGluR5- and dopamine D1
      receptor-evoked ERK1/2 phosphorylation in rat hippocampus: involvement of NMDA
      receptor.
AB  - Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic
      plasticity and cognition. We recently demonstrated that stimulation of mGluR5
      enhances NMDAR responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit,
      and this reaction was enabled by adenosine A2A receptors (A2A R) (J Neurochem,
      135, 2015, 714). In this study, by using in vitro phosphorylation and western
      blot analysis in hippocampal slices of male Wistar rats, we show that mGluR5
      stimulation or mGluR5/NMDARs co-stimulation synergistically activate ERK1/2
      signaling leading to c-Fos expression. Interestingly, both reactions are under
      the permissive control of endogenous adenosine acting through A2A Rs. Moreover,
      mGluR5-mediated ERK1/2 phosphorylation depends on NMDAR, which however exhibits a
      metabotropic way of function, since no ion influx through its ion channel is
      required. Furthermore, our results demonstrate that mGluR5 and mGluR5/NMDAR
      evoked ERK1/2 activation correlates well with the mGluR5/NMDAR-evoked
      NR2B(Tyr1472) phosphorylation, since both phenomena coincide temporally, are Src
      dependent, and are both enabled by A2A Rs. This indicates a functional
      involvement of NR2B(Tyr1472) phosphorylation in the ERK1/2 activation. Our
      biochemical results are supported by electrophysiological data showing that in
      CA1 region of hippocampus, the theta burst stimulation (TBS)-induced long-term
      potentiation coincides temporally with an increase in ERK1/2 activation and both
      phenomena are dependent on the tripartite A2A , mGlu5, and NMDARs. Furthermore,
      we show that the dopamine D1 receptors evoked ERK1/2 activation as well as the
      NR2B(Tyr1472) phosphorylation are also regulated by endogenous adenosine and A2A
      Rs. In conclusion, our results highlight the A2A Rs as a crucial regulator not
      only for NMDAR responses, but also for regulating ERK1/2 signaling and its
      downstream pathways, leading to gene expression, synaptic plasticity, and memory
      consolidation.

PMID- 29205379
TI  - In vivo measurement of swallowing by monitoring thyroid cartilage movement in
      healthy subjects using thickened liquid samples and its comparison with sensory
      evaluation.
AB  - : This research aimed to investigate the relationship between in vivo measurement
      of swallowing and sensory evaluation using thickened liquids as model foods.
      Healthy subjects (8 male and average 29.6-year old) participated in both tests,
      in which the subjects were asked to swallow the whole amount of sample (10 ml) at
      one time. In vivo measurement monitored thyroid cartilage movement during
      swallowing using a bendable pressure sensor synchronously with suprahyoid
      electromyography, whereas sensory evaluation measured perceived cohesiveness and
      adhesiveness on a visual analogue scale. Two variables from the pressure sensor
      analysis; activity of the thyroid cartilage and the maximum displacement of the
      thyroid cartilage were correlated negatively (p < .01) to perceived cohesiveness
      with high correlation coefficient (|r|> .9). Advantages of in vivo measurement
      over conventional shear rheology in assessing texture attributes perceived during
      swallowing were identified. PRACTICAL APPLICATIONS: This research provides food
      manufactures with knowledge on a novel objective method for texture measurement
      of fluid foods and beverages based on human physiology during swallowing.
      Variable from this method can work as a measure for texture design of food
      products to meet consumers' preference, particularly foods for dysphagia patients
      whose demand is increasing in this aged society although subjects of study should
      be expanded to these people in the future.

PMID- 29205378
TI  - Cardiac-gated parametric images from 82 Rb PET from dynamic frames and direct 4D
      reconstruction.
AB  - PURPOSE: Cardiac perfusion PET data can be reconstructed as a dynamic sequence
      and kinetic modeling performed to quantify myocardial blood flow, or
      reconstructed as static gated images to quantify function. Parametric images from
      dynamic PET are conventionally not gated, to allow use of all events with lower
      noise. An alternative method for dynamic PET is to incorporate the kinetic model
      into the reconstruction algorithm itself, bypassing the generation of a time
      series of emission images and directly producing parametric images. So-called
      "direct reconstruction" can produce parametric images with lower noise than the
      conventional method because the noise distribution is more easily modeled in
      projection space than in image space. In this work, we develop direct
      reconstruction of cardiac-gated parametric images for 82 Rb PET with an extension
      of the Parametric Motion compensation OSEM List mode Algorithm for Resolution
      recovery reconstruction for the one tissue model (PMOLAR-1T). METHODS: PMOLAR-1T
      was extended to accommodate model terms to account for spillover from the left
      and right ventricles into the myocardium. The algorithm was evaluated on a 4D
      simulated 82 Rb dataset, including a perfusion defect, as well as a human 82 Rb
      list mode acquisition. The simulated list mode was subsampled into replicates,
      each with counts comparable to one gate of a gated acquisition. Parametric images
      were produced by the indirect (separate reconstructions and modeling) and direct
      methods for each of eight low-count and eight normal-count replicates of the
      simulated data, and each of eight cardiac gates for the human data. For the
      direct method, two initialization schemes were tested: uniform initialization,
      and initialization with the filtered iteration 1 result of the indirect method.
      For the human dataset, event-by-event respiratory motion compensation was
      included. The indirect and direct methods were compared for the simulated dataset
      in terms of bias and coefficient of variation as a function of iteration.
      RESULTS: Convergence of direct reconstruction was slow with uniform
      initialization; lower bias was achieved in fewer iterations by initializing with
      the filtered indirect iteration 1 images. For most parameters and regions
      evaluated, the direct method achieved the same or lower absolute bias at matched
      iteration as the indirect method, with 23%-65% lower noise. Additionally, the
      direct method gave better contrast between the perfusion defect and surrounding
      normal tissue than the indirect method. Gated parametric images from the human
      dataset had comparable relative performance of indirect and direct, in terms of
      mean parameter values per iteration. Changes in myocardial wall thickness and
      blood pool size across gates were readily visible in the gated parametric images,
      with higher contrast between myocardium and left ventricle blood pool in
      parametric images than gated SUV images. CONCLUSIONS: Direct reconstruction can
      produce parametric images with less noise than the indirect method, opening the
      potential utility of gated parametric imaging for perfusion PET.

PMID- 29205380
TI  - Effect of serine protease inhibitor from squid ovary on gel properties of surimi
      from Indian mackerel.
AB  - : Effects of serine protease inhibitor from squid ovary (SOSPI) and egg white
      powder (EWP) on gel properties of surimi from Indian mackerel (Rastrelliger
      kanagurta) were investigated. Breaking force of gel increased when SOSPI levels
      increased up to 2%. However, EWP showed higher efficiency in increasing breaking
      force of resulting surimi gel. Nevertheless, SOSPI (0.5-3%) had no effect on
      deformation. Trichloroacetic acid-soluble peptide content in surimi gel decreased
      when the levels of SOSPI and EWP increased (p < .05). This was coincidental with
      more retained myosin heavy chain. Water holding capacity was increased with the
      addition of these protein additives, but resulted in lower whiteness.
      Microstructure study revealed that surimi gel added with 2% EWP was denser and
      had higher connectivity as compared to that containing 2% SOSPI. The SOSPI had no
      negative effect on sensory attributes and could serve as the alternative protein
      additive to improve gel strength of surimi. PRACTICAL APPLICATIONS: Surimi from
      dark-fleshed fish is prone to degradation of myofibrillar proteins caused by the
      endogenous proteases, thereby lowering textural property. To tackle the problem,
      protease inhibitors (egg white, porcine plasma protein, and bovine plasma
      protein) have been used by the surimi industries. Due to drawbacks of some
      particular inhibitors (religious constraints, off-white color, off odor, etc.),
      the novel additives are still in demand. Ovary from squid processing industry,
      commonly discarded as the waste, can be an alternative natural protease
      inhibitor, which can improve the gel properties of surimi, especially produced
      from dark-fleshed fish.

PMID- 29205381
TI  - The extrusion test and sensory perception revisited: Some comments on generality
      and the effect of measurement temperature.
AB  - : Relations between sensory perception, extrusion and fracture in shear,
      extension and compression are examined. Gelatin-based gels are perceived as less
      firm and less hard than expected based on their mechanical properties compared to
      polysaccharide gels that have the same mechanical properties at room temperature
      but melt well above body temperature, underlying the importance of the
      measurement temperature for gels that melt during mastication. Correlations
      between parameters from extrusion and compression, extension and shear are
      verified using mixed polysaccharide gels. PRACTICAL APPLICATIONS: We previously
      reported a high correlation between several sensory attributes and parameters
      from an extrusion test. The extrusion test showed the most robust correlation,
      and could be used to assess samples at both extremes of the texture range with
      respect to elasticity, for example, both samples that could not be extended as
      their very low elasticity led to their fracture during handling, as well as
      samples that could not be fractured in compression. Here, we reexamine the
      validity of the relations reported. We demonstrate the generality of the
      relations between large deformation tests and extrusion, but the findings
      underscore the need to take into account the measurement temperature for samples
      that melt during mastication when correlating instrumental parameters with
      sensory perception.

PMID- 29205382
TI  - The relationship between transpiration and nutrient uptake in wheat changes under
      elevated atmospheric CO2.
AB  - The impact of elevated [CO2 ] (e[CO2 ]) on crops often includes a decrease in
      their nutrient concentrations where reduced transpiration-driven mass flow of
      nutrients has been suggested to play a role. We used two independent approaches,
      a free-air CO2 enrichment (FACE) experiment in the South Eastern wheat belt of
      Australia and a simulation study employing the agricultural production systems
      simulator (APSIM), to show that transpiration (mm) and nutrient uptake (g m-2 )
      of nitrogen (N), potassium (K), sulfur (S), calcium (Ca), magnesium (Mg) and
      manganese (Mn) in wheat are correlated under e[CO2 ], but that nutrient uptake
      per unit water transpired is higher under e[CO2 ] than under ambient [CO2 ]
      (a[CO2 ]). This result suggests that transpiration-driven mass flow of nutrients
      contributes to decreases in nutrient concentrations under e[CO2 ], but cannot
      solely explain the overall decline.

PMID- 29205383
TI  - Elucidating the molecular mechanisms mediating plant salt-stress responses.
AB  - Contents Summary 523 I. Introduction 523 II. Sensing salt stress 524 III. Ion
      homeostasis regulation 524 IV. Metabolite and cell activity responses to salt
      stress 527 V. Conclusions and perspectives 532 Acknowledgements 533 References
      533 SUMMARY: Excess soluble salts in soil (saline soils) are harmful to most
      plants. Salt imposes osmotic, ionic, and secondary stresses on plants. Over the
      past two decades, many determinants of salt tolerance and their regulatory
      mechanisms have been identified and characterized using molecular genetics and
      genomics approaches. This review describes recent progress in deciphering the
      mechanisms controlling ion homeostasis, cell activity responses, and epigenetic
      regulation in plants under salt stress. Finally, we highlight research areas that
      require further research to reveal new determinants of salt tolerance in plants.

PMID- 29205385
TI  - Simulator-based occupational therapy driving intervention can reduce driving
      errors on a simulator-based driving assessment in combat veterans with
      polytrauma.

PMID- 29205386
TI  - Editorial: Sylvia Docker Lecture Award Silver Jubilee.

PMID- 29205387
TI  - Partnership, inclusion and innovation in occupational therapy: Essential or
      optional ingredients to flourish in a changing environment?
AB  - BACKGROUND/AIM: Historically occupational therapy has evidenced a tenacity to
      adjust and adapt to societal changes. Currently in Australia we are in the midst
      of significant change in health, disability and aged care service delivery
      alongside increasing numbers of new graduates seeking employment. Both of these
      changes create challenges and opportunities for the profession. How the
      profession adjusts to new service delivery models and supports new graduates in
      this changing work environment will influence our future. METHODS: Using examples
      from practice the paper explores ways in which partnership, inclusion and
      innovation can be effective in a changing environment. RESULTS: Doing effective
      partnership takes time, energy and a shared commitment of all involved and often
      requires negotiations and compromise. Inclusion can be tricky and requires
      vigilance and ongoing reflection on actions to determine if the outcomes are what
      was intended. Innovation can play two roles; it can be used to conserve current
      practice in new ways or it can offer agency to disrupt and redefine practice.
      CONCLUSION: The way in which the profession chooses to enact partnerships and
      inclusion will play a vital role in shaping the future. Similarly the space and
      support made for conservative or disruptive innovation will determine how we
      choose to define ourselves going forward. Moreover, these choices and actions
      will govern how effective we are in navigating the changing environment and
      supporting new graduates transitioning into the profession.

PMID- 29205388
TI  - Intelligent Assistive Technology for people living with dementia is a rapidly
      growing and changing area requiring clinical consideration.

PMID- 29205389
TI  - Early intervention: The challenge to find the best approach for infant and
      family.

PMID- 29205390
TI  - Sustaining global agriculture through rapid detection and deployment of genetic
      resistance to deadly crop diseases.
AB  - Contents Summary 45 I. Introduction 45 II. Targeted chromosome-based cloning via
      long-range assembly (TACCA) 46 III. Resistance gene cloning through mutational
      mapping (MutMap) 47 IV. Cloning through mutant chromosome sequencing
      (MutChromSeq) 47 V. Rapid cloning through resistance gene enrichment and
      sequencing (RenSeq) 49 VI. Cloning resistance genes through transcriptome
      profiling (RNAseq) 49 VII. Resistance gene deployment strategies 49 VIII.
      Conclusions 50 Acknowledgements 50 References 50 SUMMARY: Genetically encoded
      resistance is a major component of crop disease management. Historically, gene
      loci conferring resistance to pathogens have been identified through classical
      genetic methods. In recent years, accelerated gene cloning strategies have become
      available through advances in sequencing, gene capture and strategies for
      reducing genome complexity. Here, I describe these approaches with key emphasis
      on the isolation of resistance genes to the cereal crop diseases that are an
      ongoing threat to global food security. Rapid gene isolation enables their
      efficient deployment through marker-assisted selection and transgenic technology.
      Together with innovations in genome editing and progress in pathogen virulence
      studies, this creates further opportunities to engineer long-lasting resistance.
      These approaches will speed progress towards a future of farming using fewer
      pesticides.

PMID- 29205391
TI  - Association of palatine tonsil size and obstructive sleep apnea in adults.
AB  - OBJECTIVE: The relationship between palatine tonsil (PT) size and obstructive
      sleep apnea (OSA) has not been well established in adults. The purpose of this
      study was to test the association between PT grade, PT volume, and OSA severity
      in U.S. adult patients. STUDY DESIGN: Cross-sectional study of all patients (age
      >= 18 years) who underwent pharyngeal surgery for OSA that included palatine
      tonsillectomy with tonsil volume measurement from January 2011 to June 2016.
      METHODS: Medical records were reviewed for PT grade (measured on clinical exam by
      the Brodsky tonsil grading scale), PT volume (measured intraoperatively by water
      displacement), and apnea-hypopnea index (AHI). Associations were evaluated with
      multivariate linear regression adjusting for age, sex, body mass index (BMI),
      smoking status, lingual tonsil volume (AHI models only), and multilevel surgery
      aside from lingual tonsillectomy (PT volume vs. AHI model only). RESULTS: The
      cohort (N = 83) was middle-aged (mean age 43 +/- 12 years), predominantly male
      (61%), obese (mean BMI 33 +/- 7 kg/m2 ), and had severe OSA (mean AHI 32 +/- 28).
      After adjustment for confounders, PT grade was strongly associated with PT volume
      (beta = 1.8, 95% confidence interval [CI]: [1.0, 2.6], P < 0.001) and with AHI
      (beta = 13.5, 95% CI: [3.5, 23.6], P = 0.01); PT volume was not associated with
      AHI (beta = -0.2, 95% CI: [-2.2, 1.9], P = 0.89). CONCLUSION: In contrast to past
      studies, subjective PT grade (vs. objective PT volume) was more strongly
      associated with AHI. These data suggest the space that the tonsils occupy within
      the oropharyngeal airway, instead of their actual measured volume, may be more
      predictive of OSA severity in a cohort of U.S. adult patients. LEVEL OF EVIDENCE:
      2c. Laryngoscope, 128:1002-1006, 2018.

PMID- 29205392
TI  - Toward quantitative fast diffusion kurtosis imaging with b-values chosen in
      consideration of signal-to-noise ratio and model fidelity.
AB  - PURPOSE: Diffusion kurtosis (DK) imaging is a variant of conventional diffusion
      magnetic resonance (MR) imaging that allows assessment of non-Gaussian diffusion.
      Fast DK imaging expedites the procedure by decreasing both scan time (acquiring
      the minimally required number of b-values) and computation time (obviating least
      square curve fitting). This study aimed to investigate the applicability of fast
      DK imaging for both cerebral gray matter and white matter as a quantitative
      method. METHODS: Seventeen healthy volunteers were recruited and each provided
      written informed consent before participation. On a 3-Tesla clinical MR system,
      diffusion imaging was performed with 12 b-values ranging from 0 to 4000 s/mm2 .
      Diffusion encoding was along three orthogonal directions (slice selection, phase
      encoding, and frequency encoding) in separate series. Candidate b-values were
      chosen by first determining the maximum b-value (bmax ) in the context of signal
      to-noise ratio and then assessing the model fidelity for all b-value combinations
      within bmax . Diffusion coefficient (D) and diffusion kurtosis coefficient (K)
      were derived from these candidates and assessed for their dependence on b-value
      combination. RESULTS: Our data suggested bmax to be 2200 s/mm2 as a trade-off
      between the percentage (~80%) of voxels statistically detectable against
      background and the sensitivity to non-Gaussian diffusion in both gray matter and
      white matter. The measurement dependence on b-value was observed predominantly in
      areas with a considerable amount of cerebrospinal fluid. In most gray matter and
      white matter, b-value combinations do not cause statistical difference in the
      calculated D and K. CONCLUSIONS: For fast DK imaging to be quantitatively
      applicable in both gray matter and white matter, bmax should be chosen to ensure
      adequate signal-to-noise ratio in the majority of gray/white matter and the two
      nonzero b-values should be chosen in consideration of model fidelity to mitigate
      the dependence of derived indices on b-values.

PMID- 29205393
TI  - EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.
AB  - Food allergy can result in considerable morbidity, impairment of quality of life,
      and healthcare expenditure. There is therefore interest in novel strategies for
      its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral
      (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared
      by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on
      Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence
      based recommendations for active treatment of IgE-mediated food allergy with FA
      AIT. Immunotherapy relies on the delivery of gradually increasing doses of
      specific allergen to increase the threshold of reaction while on therapy (also
      known as desensitization) and ultimately to achieve post-discontinuation
      effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA
      AIT has most frequently been assessed: here, the allergen is either immediately
      swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall,
      trials have found substantial benefit for patients undergoing either OIT or SLIT
      with respect to efficacy during treatment, particularly for cow's milk, hen's
      egg, and peanut allergies. A benefit post-discontinuation is also suggested, but
      not confirmed. Adverse events during FA-AIT have been frequently reported, but
      few subjects discontinue FA-AIT as a result of these. Taking into account the
      current evidence, FA-AIT should only be performed in research centers or in
      clinical centers with an extensive experience in FA-AIT. Patients and their
      families should be provided with information about the use of FA-AIT for IgE
      mediated food allergy to allow them to make an informed decision about the
      therapy.

PMID- 29205394
TI  - Vessel sealer and divider instrument temperature during laparoscopic ovariectomy
      in horses.
AB  - OBJECTIVE: To determine the temperature of a vessel sealer and divider device
      during unilateral paralumbar laparoscopic ovariectomy in standing, sedated mares.
      STUDY DESIGN: Prospective study. ANIMALS: Fifteen healthy research mares.
      METHODS: Healthy mares with normal ovarian palpation and ultrasonographic
      appearance were enrolled. Horses were restrained in standing stocks and sedated.
      A right or left paralumbar ovariectomy was performed with a laparoscopic portal
      and 2 instrument portals. Ovaries were excised with traumatic forceps and a blunt
      tip vessel sealer and divider. Temperatures of the vessel sealer and divider were
      recorded with a thermocouple device adhered to the tip of the instrument.
      Variables were reported as median and interquartile range (IQR). RESULTS:
      Surgical time was 30 minutes (IQR, 25-32) including use of the vessel sealer and
      the divider for 4.1 minutes (IQR, 3.2-5.8). The tip of the instrument reached
      temperatures of 77 degrees C (IQR, 72-85) during activation and 64 degrees C
      (IQR, 61-67) at end cycle. The median increase in end-cycle instrument tip
      temperature per activation cycle was 2 degrees C (IQR, -1-6). All mares returned
      to their intended use. CONCLUSION: Despite the instrument temperatures observed
      during unilateral laparoscopic ovariectomy, surgical complications were minimal.
      The clinical relevance of the increase in instrument tip temperature of the
      vessel sealer and divider is presently unclear, but surgeons should use the
      instrument with caution, especially in close proximity to viscera. The increase
      in temperature observed at the tip of the vessel sealer and divider during
      unilateral ovariectomy could be associated with morbidity. The clinical relevance
      of instrument tip heating during other procedures, such as adhesiolysis and
      intestinal resection, is unknown and should be evaluated.

PMID- 29205395
TI  - Contribution of skin and stone to texture measurements of spherical model fruits.
AB  - : Fruits are composite materials often surrounded by a skin and sometimes
      containing rigid stones (pits). To understand the contribution of skin and stone
      to the overall texture of the fruit, model fruits were constructed from molded
      gelatin spheres, with rigid inclusions and a skin layer. Cross polarized light
      revealed the stress distribution during puncture testing and the mechanical
      measures of firmness, Poisson's ratio and breaking force were determined. Skin
      significantly raised the breaking force. Spherical stones raised the firmness
      effectively reducing the deformable material in the sphere, resulting in inflated
      strains. Disc shaped stones compared with spherical ones, with the narrow edge
      normal to the force acted like an internal blade and significantly lowered the
      breaking force. Neither skin nor stone had any significant impact on Poisson's
      ratio. Three examples of real fruit (raspberries, grapes, and cherries) were
      tested to contextualize the findings. PRACTICAL APPLICATIONS: Consumers gently
      squeeze fruit to gauge ripeness. Unwittingly, what we perceive while squeezing
      fruit is not wholly dependent on the texture of the internal flesh. In this work,
      we have attempted to model how the firmness and breaking force are influenced by
      the presence of a skin and stones of various size and shape. This has
      implications in both sensory and instrumental fruit testing.

PMID- 29205396
TI  - Imaging-based predictors of permanent pacemaker implantation after transcatheter
      aortic valve replacement.
AB  - BACKGROUND: Cardiac conduction abnormalities requiring permanent pacemaker (PPM)
      implantation are major complications of transcatheter aortic valve replacement
      (TAVR). We aimed to investigate whether the relationship between prosthetic valve
      size and cardiac-gated computed tomography (CT)-based aortic root complex
      measurements can aid in recognizing patients at risk for PPM implantation post
      TAVR. METHODS: We included 83 of 114 consecutive patients who underwent TAVR with
      the Edwards Sapien valve (Edwards Lifesciences, Irving, CA, USA) at our
      institution. We excluded patients with preexisting PPM, patients who required
      conversion to an open surgical procedure, and patients without CT data. We
      assessed the significance of various potential predictors of PPM placement post
      TAVR. RESULTS: Following TAVR, eight patients (9.6%) required PPM. Prosthetic
      valve to sinus of Valsalva (SOV) index was significantly higher in those patients
      requiring a PPM post-TAVR (84.1 +/- 9.3 vs 76.8 +/- 7.1, P  =  0.009).
      CONCLUSIONS: The prosthetic valve size to diameter of SOV index was identified as
      a novel predictor of PPM implantation after TAVR.

PMID- 29205398
TI  - Nerve ultrasound in polyneuropathies.
AB  - Ultrasound can be used to visualize pathology in the peripheral nerves of
      patients with polyneuropathy. Nerve enlargement is the most frequent pathology,
      but other abnormalities, including abnormal nerve echogenicity and vascularity,
      are also encountered. This monograph presents an overview of the role of nerve
      ultrasound in the evaluation and management of both inherited and acquired
      polyneuropathies. A description of the sonographic techniques and common
      abnormalities is provided, followed by a presentation of typical findings in
      different neuropathies. Scoring systems for characterizing the presence and
      pattern of nerve abnormalities as they relate to different polyneuropathies are
      presented. Muscle Nerve 57: 716-728, 2018.

PMID- 29205399
TI  - Species selection under long-term experimental warming and drought explained by
      climatic distributions.
AB  - Global warming and reduced precipitation may trigger large-scale species losses
      and vegetation shifts in ecosystems around the world. However, currently lacking
      are practical ways to quantify the sensitivity of species and community
      composition to these often-confounded climatic forces. Here we conducted long
      term (16 yr) nocturnal-warming (+0.6 degrees C) and reduced precipitation (-20%
      soil moisture) experiments in a Mediterranean shrubland. Climatic niche groups
      (CNGs) - species ranked or classified by similar temperature or precipitation
      distributions - informatively described community responses under experimental
      manipulations. Under warming, CNGs revealed that only those species distributed
      in cooler regions decreased. Correspondingly, under reduced precipitation, a U
      shaped treatment effect observed in the total community was the result of an
      abrupt decrease in wet-distributed species, followed by a delayed increase in dry
      distributed species. Notably, while partially correlated, CNG explanations of
      community response were stronger for their respective climate parameter,
      suggesting some species possess specific adaptations to either warming or drought
      that may lead to independent selection to the two climatic variables. Our
      findings indicate that when climatic distributions are combined with experiments,
      the resulting incorporation of local plant evolutionary strategies and their
      changing dynamics over time leads to predictable and informative shifts in
      community structure under independent climate change scenarios.

PMID- 29205397
TI  - Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene
      Expression and Heteroreceptor Complexes in the Striatum in Rats.
AB  - BACKGROUND: Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been
      demonstrated in the striatum of humans with alcohol use disorder (AUD). The
      attenuated D2R binding has been suggested to reflect a reduced D2R density, which
      in turn has been proposed to drive craving and relapse. However, results from
      rodent studies addressing the effects of alcohol drinking on D2R density have
      been inconsistent. METHODS: A validated alcohol drinking model (intermittent
      access to 20% alcohol) in Wistar rats was used to study the effects of voluntary
      alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age
      matched alcohol-naive control rats. Reverse transcriptase quantitative PCR was
      used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite
      pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene
      were determined. In situ proximity ligation assay was used to measure densities
      of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R, and sigma1
      receptor (sigma1R)-D2R. RESULTS: Long-term voluntary alcohol drinking
      significantly reduced mRNA levels of the long D2R isoform in the nucleus
      accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence
      of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R
      homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor
      complexes in the NAc shell and the dorsal striatum, and decreased the density of
      sigma1R-D2R heteroreceptor complexes in the dorsal striatum. CONCLUSIONS: The
      present results on long-term alcohol drinking might reflect reduced D2R levels
      through reductions in D2R-D2R homoreceptor complexes and gene expression.
      Furthermore, based on antagonistic interactions between A2AR and D2R, an
      increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced
      affinity and signaling of the D2R population within the complex. Hence, both
      reduced striatal D2R levels and reduced D2R protomer affinity within the striatal
      A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with
      AUD. This supports the hypothesis of a hypodopaminergic system in AUD and
      suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment
      target.

PMID- 29205400
TI  - Severe asymmetric muscle weakness revealing glycogenin-1 polyglucosan body
      myopathy.

PMID- 29205401
TI  - How many proteins can be identified in a 2DE gel spot within an analysis of a
      complex human cancer tissue proteome?
AB  - Two-dimensional gel electrophoresis (2DE) in proteomics is traditionally assumed
      to contain only one or two proteins in each 2DE spot. However, 2DE resolution is
      being complemented by the rapid development of high sensitivity mass
      spectrometers. Here we compared MALDI-MS, LC-Q-TOF MS and LC-Orbitrap Velos MS
      for the identification of proteins within one spot. With LC-Orbitrap Velos MS
      each Coomassie Blue-stained 2DE spot contained an average of at least 42 and 63
      proteins/spot in an analysis of a human glioblastoma proteome and a human
      pituitary adenoma proteome, respectively, if a single gel spot was analyzed. If a
      pool of three matched gel spots was analyzed this number further increased up to
      an average of 230 and 118 proteins/spot for glioblastoma and pituitary adenoma
      proteome, respectively. Multiple proteins per spot confirm the necessity of
      isotopic labeling in large-scale quantification of different protein species in a
      proteome. Furthermore, a protein abundance analysis revealed that most of the
      identified proteins in each analyzed 2DE spot were low-abundance proteins. Many
      proteins were present in several of the analyzed spots showing the ability of 2DE
      MS to separate at the protein species level. Therefore, 2DE coupled with high
      sensitivity LC-MS has a clearly higher sensitivity as expected until now to
      detect, identify and quantify low abundance proteins in a complex human proteome
      with an estimated resolution of about 500 000 protein species. This clearly
      exceeds the resolution power of bottom-up LC-MS investigations.

PMID- 29205402
TI  - Detection and molecular characterization of betanodaviruses retrieved from
      bivalve molluscs.
AB  - Betanodaviruses are small ssRNA viruses responsible for viral encephalopathy and
      retinopathy, otherwise known as viral nervous necrosis, in marine fish worldwide.
      These viruses can be either horizontally or vertically transmitted and have been
      sporadically detected in invertebrates, which seem to be one of the possible
      viral sources. Twenty-eight new betanodavirus strains were retrieved in three
      molluscs species collected from different European countries between 2008 and
      2015. The phylogenetic analyses revealed that strains retrieved from bivalve
      molluscs are closely related to viruses detected in finfish in Southern Europe in
      the period 2000-2009. Nevertheless, a new betanodavirus strain, markedly
      different from the other members of the RGNNV genotype, was detected. Such a
      massive and varied presence of betanodaviruses in bivalve molluscs greatly
      stresses the risks of transmission previously feared for other invertebrates.
      Bivalve molluscs reared in the same area as farmed and wild finfish could act as
      a reservoir of the virus. Furthermore, current European regulations allow
      relaying activities and the sale of live bivalve molluscs, which could pose a
      real risk of spreading betanodaviruses across different geographic regions. To
      our knowledge, this is the first study, which focuses on the detection and
      genetic characterization of betanodaviruses in bivalve molluscs.

PMID- 29205403
TI  - Increased Th17 functions are accompanied by Tregs activities in lupoid
      leishmaniasis.
AB  - The immunopathogenesis of lupoid leishmaniasis is challenging. Although an
      appropriate immune response is critical for controlling these parasites,
      inappropriate inflammatory reactions can also promote increased pathology. The
      role of immune modulatory effect of the main transcription factors and cytokines
      of T regulatory and Th17 cells in pathogenesis of leishmaniasis chronicity was
      investigated in this study. The gene expression of interleukin-10 (IL-10),
      transforming growth factor-beta (TGF-beta1), forkhead box P3 (Foxp3), interleukin
      17(IL-17A) and retinoic acid-related orphan receptor gamma t (ROrC) was assessed
      in peripheral blood mononuclear cells of eighty blood samples from cutaneous
      leishmaniasis (CL) patients with usual lesions (n = 31), lupoid lesions (n = 29)
      and healthy volunteers (n = 20). Quantitative relative real-time PCR (qRT-PCR)
      was performed using the Taqman and Sybergreen methods for expression of target
      genes. Expression of Foxp3 (P = .013), IL-10 (P < .001) and IL-17A (P < .001) was
      significantly higher in lupoid patient compare to the nonlupoid group. Expression
      of Foxp3 (P < .001), IL-10 (P < .001) and IL-17A (P = .033) was significantly
      more in nonlupoid subjects than in healthy volunteers, except for RORgammat.
      These findings suggest that Foxp3+ cells, IL-10 and IL-17 play important roles in
      the immunopathogenesis of CL and that these roles differ depending on the causal
      leishmania species and different body compartments.

PMID- 29205404
TI  - A quilting subcutaneous suture pattern to reduce seroma formation and pain 24
      hours after midline celiotomy in dogs: A randomized controlled trial.
AB  - OBJECTIVE: To determine the influence of a quilting suture pattern tacking the
      subcutaneous tissues to the deep fascia on complications after midline celiotomy
      in dogs. STUDY DESIGN: Single-center, randomized, blinded, controlled trial
      conducted in a veterinary teaching hospital. ANIMALS: Four hundred thirty-two
      dogs undergoing midline celiotomy for ovariohysterectomy (n = 249) or other
      abdominal procedures (n = 183). METHODS: Dogs were randomly assigned to (1) a
      quilting group, subcutaneous tissue with apposition plus tacking to the rectus
      fascia or (2) a nonquilting group, with apposition of subcutaneous tissue without
      tacking. Randomization was stratified on hospital admitting service. Primary
      outcome was the incidence of incisional seroma. Secondary outcomes included
      postoperative pain the day after surgery and surgical site infection (SSI).
      Outcomes were assessed during the first 30 postoperative days. RESULTS: No
      differences were detected between the quilting group (n = 183) and the
      nonquilting group (n = 175) in terms of illness severity, surgical procedure
      performed, surgeon's experience, duration of surgery, intraoperative
      complications, or methods of surgical closure other than the intervention under
      study. In an intent-to-treat analysis, the incidence of incisional seroma was
      lower in the quilting group (odds ratio = 0.30, 95% CI = 0.13-0.67, P = .004).
      Pain assessed 24 hours postoperatively was lower in the quilting group (P = .03).
      The incidence of SSI did not differ between groups. CONCLUSION: Tacking the
      subcutaneous tissues to the deep fascia is indicated to reduce seroma during
      celiotomy closure.

PMID- 29205405
TI  - Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does
      not change the short-term risk for de novo hepatocellular carcinoma in patients
      with liver cirrhosis.
AB  - BACKGROUND: Hepatitis C virus (HCV) clearance with IFN-based therapies reduces
      the incidence of hepatocellular carcinoma (HCC). There has been some debate if
      IFN-free therapy with direct-acting antivirals alters the risk for HCC. AIM: To
      investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with
      direct-acting antivirals vs untreated controls. METHODS: We prospectively
      monitored 373 patients with chronic hepatitis C who received IFN-free therapies
      with direct-acting antiviral after January 2014. A retrospective control cohort
      of untreated cirrhotic patients was recruited out of 3715 HCV patients who were
      followed at our centre between 2007 and 2013, with similar HCC screening
      protocols. RESULTS: 158 direct-acting antiviral-treated and 184 control patients
      with liver cirrhosis were included in this analysis. The groups did not differ in
      gender and genotype distribution, severity of liver disease and prevalence of
      diabetes mellitus. Patients were followed up for a median of 440 (range 91-908)
      and 592 (range 90-1000) days. HCCs developed in 6 and 14 patients during follow
      up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the
      direct-acting antiviral-treated group, there was no new case of HCC later than
      450 days after treatment initiation. In multivariate analysis, higher MELD-Scores
      and AFP-levels were independently associated with HCC development. Transplant
      free patient survival was similar in both groups. CONCLUSIONS: IFN-free direct
      acting antiviral therapy of chronic hepatitis C does not alter the short-term
      risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become
      evident after more than 1.5 years of follow-up.

PMID- 29205406
TI  - Systematic review with network meta-analysis: first- and second-line
      pharmacotherapy for moderate-severe ulcerative colitis.
AB  - BACKGROUND: There are limited data to inform positioning of agents for treating
      moderate-severe ulcerative colitis (UC). AIM: To assess comparative efficacy and
      safety of different therapies as first-line (biologic-naive) and second-line
      (prior exposure to anti-tumour necrosis factor(TNF)-alpha) agents for moderate
      severe UC, through a systematic review and network meta-analysis, and appraise
      quality of evidence (QoE) using grading of recommendations, assessment,
      development and evaluation (GRADE) approach. METHODS: We identified randomised
      controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF
      agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or
      second-line agents, and compared with placebo or another active agent. Efficacy
      outcomes were induction/maintenance of remission and mucosal healing; and safety
      outcomes were serious adverse events and infections. Network meta-analyses were
      performed, and ranking was assessed using surface under the cumulative ranking
      (SUCRA) probabilities. RESULTS: In biologic-naive patients (12 trials, no head-to
      head comparisons), infliximab and vedolizumab were ranked highest for induction
      of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence
      intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal
      healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In
      patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons),
      tofacitinib was ranked highest for induction of clinical remission (OR, 11.88
      [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in
      trial design limited comparability of trials of maintenance therapy for efficacy.
      Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91),
      and infection (SUCRA, 0.75) in maintenance trials. CONCLUSIONS: Infliximab and
      vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked
      highest as second-line agent, for induction of remission and mucosal healing in
      patients with moderate-severe UC, based on indirect comparisons. Head-to-head
      trials are warranted to inform clinical decision-making with greater confidence.

PMID- 29205407
TI  - Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and
      Kinetics in the Rat Brain.
AB  - BACKGROUND: Ethanol (EtOH) intoxication inhibits glucose transport and decreases
      overall brain glucose metabolism; however, humans with long-term EtOH consumption
      were found to have a significant increase in [1-11 C]-acetate uptake in the
      brain. The relationship between the cause and effect of [1-11 C]-acetate kinetics
      and acute/chronic EtOH intoxication, however, is still unclear. METHODS: [1-11 C]
      acetate positron emission tomography (PET) with dynamic measurement of K1 and k2
      rate constants was used to investigate the changes in acetate metabolism in
      different brain regions of rats with acute or chronic EtOH intoxication. RESULTS:
      PET imaging demonstrated decreased [1-11 C]-acetate uptake in rat brain with
      acute EtOH intoxication, but this increased with chronic EtOH intoxication.
      Tracer uptake rate constant K1 and clearance rate constant k2 were decreased in
      acutely intoxicated rats. No significant change was noted in K1 and k2 in chronic
      EtOH intoxication, although 6 of 7 brain regions showed slightly higher k2 than
      baseline. These results indicate that acute EtOH intoxication accelerated acetate
      transport and metabolism in the rat brain, whereas chronic EtOH intoxication
      status showed no significant effect. CONCLUSIONS: In vivo PET study confirmed the
      modulatory role of EtOH, administered acutely or chronically, in [1-11 C]-acetate
      kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the
      transport and metabolism of acetate in the brain, whereas chronic EtOH exposure
      may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1-11
      C]-acetate PET imaging is a feasible approach to study the effect of EtOH on
      acetate metabolism in rat brain.

PMID- 29205408
TI  - Ovarian Hormones Contribute to High Levels of Binge-Like Drinking by Female Mice.
AB  - BACKGROUND: Recently, the incidence of binge drinking by women has increased.
      Binge drinking is detrimental to women's health, yet the biological mechanisms
      that promote excessive drinking by women are not well understood. One method of
      assessing binge-like ethanol (EtOH) consumption in mice is the drinking in the
      dark (DID) test, in which mice drink sufficient EtOH to achieve intoxication. In
      this study, we directly compared male, female, and ovariectomized (OVX) mice for
      DID and tested whether 17beta-estradiol (E2) contributes to DID. We also measured
      whether DID varies throughout the estrous cycle and whether repeated intermittent
      DID impacts the estrous cycle. METHODS: Male, female, and OVX C57BL/6J mice were
      tested for DID for 2 hours per day on days 1 to 3 and for 4 hours on day 4 using
      a single bottle containing 20% EtOH. To measure the effects of E2 on DID, OVX
      mice were treated with estradiol benzoate (EB) or vehicle daily starting 2 weeks
      prior to the drinking test and throughout the DID procedure. In a separate group
      of experiments, EtOH consumption and estrous cycle phase were measured in freely
      cycling mice that were drinking EtOH or water 5 days per week for 2 or 6 weeks.
      RESULTS: Female mice consumed more EtOH than male and OVX mice. Treatment with EB
      increased EtOH consumption by OVX mice compared with vehicle-treated controls.
      However, EtOH intake did not vary across the estrous cycle, nor did long-term DID
      alter the estrous cycle. CONCLUSIONS: These results demonstrate that ovarian
      hormones, specifically E2, contribute to increased EtOH consumption by female
      mice in the DID test. Although ovarian hormones contribute to this behavior, EtOH
      consumption is not affected by estrous cycle phase in freely cycling mice. This
      study provides a framework for understanding the factors that contribute to binge
      drinking in females.

PMID- 29205409
TI  - Inverse probability weighting to control confounding in an illness-death model
      for interval-censored data.
AB  - Multistate models with interval-censored data, such as the illness-death model,
      are still not used to any considerable extent in medical research regardless of
      the significant literature demonstrating their advantages compared to usual
      survival models. Possible explanations are their uncommon availability in
      classical statistical software or, when they are available, by the limitations
      related to multivariable modelling to take confounding into consideration. In
      this paper, we propose a strategy based on propensity scores that allows
      population causal effects to be estimated: the inverse probability weighting in
      the illness semi-Markov model with interval-censored data. Using simulated data,
      we validated the performances of the proposed approach. We also illustrated the
      usefulness of the method by an application aiming to evaluate the relationship
      between the inadequate size of an aortic bioprosthesis and its degeneration
      or/and patient death. We have updated the R package multistate to facilitate the
      future use of this method.

PMID- 29205410
TI  - Eating pathology in midlife women: Similar or different to younger counterparts?
AB  - OBJECTIVE: This study examined potential similarities and differences between
      women with eating disorders (EDs) in midlife and their younger counterparts.
      METHOD: Seven hundred and three women assessed by a specialist eating disorder
      service were divided into three groups based on age (18-25, 25-40, and 40+) and
      compared on a number of clinical and demographic measures. Distribution of ED
      diagnoses was also examined between groups. RESULTS: Midlife women were less
      likely to receive a diagnosis of anorexia nervosa and more likely to receive a
      diagnosis of binge-eating disorder than their younger counterparts. Duration of
      illness was longer and age of ED onset later in the midlife group but no
      differences were seen on measures of global ED pathology, psychosocial
      impairment, or psychological distress. DISCUSSION: This study adds to the
      developing literature concerning EDs in midlife women, although further work is
      needed to support the findings presented here and to examine profiles of males
      presenting to treatment centers.

PMID- 29205411
TI  - The nonalcoholic steatohepatitis metabotype: Imbalance of circulating amino acids
      and transamination reactions reflect impaired mitochondrial function.

PMID- 29205412
TI  - Temporal distribution of, and effect of anthropic modifications on, phlebotomine
      populations in the Chaco Bioregion, Argentina.
AB  - Migonemyia migonei is the predominant species in the dry ecoregion and Nyssomyia
      neivai in the humid region, although co-dominance in humid highly modified areas
      could be observed. Vector abundance seems to be modulated by environmental
      anthropization, as the abundance and predominance of Ny. neiviai and Mg. migonei
      increased in highly modified areas. In Humid Chaco, the risk of human-vector
      contact would be present throughout the year, being particularly high in
      spring/summer, and in Dry Chaco, the risk would be restricted to temperate and
      humid months.

PMID- 29205413
TI  - Gentle palpating liver sinusoidal endothelial cells reveals the dynamic behavior
      and formation of fenestrae: A new window for biomedical research.

PMID- 29205414
TI  - A joint marginal-conditional model for multivariate longitudinal data.
AB  - Multivariate longitudinal data frequently arise in biomedical applications;
      however, their analyses are often performed one outcome at a time, or jointly
      using existing software in an ad hoc fashion. A main challenge in the proper
      analysis of such data is the fact that the different outcomes are measured on
      different unknown scales. Methodology for handling the scale problem has been
      previously proposed for cross-sectional data, and here we extend it to the
      longitudinal setting. We consider modeling the longitudinal data using random
      effects, while leaving the joint distribution of the multiple outcomes
      unspecified. We propose an estimating equation together with an expectation
      maximization-type (expectation-substitution) algorithm. The consistency and the
      asymptotic distribution of the parameter estimates are established. The method is
      evaluated using extensive simulations and applied to a longitudinal nutrition
      data set from a large dietary intervention trial on breast cancer survivors, the
      Women's Healthy Eating and Living Study.

PMID- 29205415
TI  - Systematic review: human gut dysbiosis induced by non-antibiotic prescription
      medications.
AB  - BACKGROUND: Global prescription drug use has been increasing continuously for
      decades. The gut microbiome, a key contributor to health status, can be altered
      by prescription drug use, as antibiotics have been repeatedly described to have
      both short-term and long-standing effects on the intestinal microbiome. AIM: To
      summarise current findings on non-antibiotic prescription-induced gut microbiome
      changes, focusing on the most frequently prescribed therapeutic drug categories.
      METHODS: We conducted a systematic review by first searching in online databases
      for indexed articles and abstracts in accordance with PRISMA guidelines. Studies
      assessing the intestinal microbiome alterations associated with proton pump
      inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs),
      opioids, statins and antipsychotics were included. We only included studies using
      culture-independent molecular techniques. RESULTS: Proton pump inhibitors and
      antipsychotic medications are associated with a decrease in alpha diversity in
      the gut microbiome, whereas opioids were associated with an increase in alpha
      diversity. Metformin and NSAIDs were not associated with significant changes in
      alpha diversity. beta diversity was found to be significantly altered with all
      drugs, except for NSAIDs. PPI use was linked to a decrease in Clotridiales and
      increase in Actinomycetales, Micrococcaceae and Streptococcaceae, which are
      changes previously implicated in dysbiosis and increased susceptibility to
      Clostridium difficile infection. Consistent results showed that PPIs, metformin,
      NSAIDs, opioids and antipsychotics were either associated with increases in
      members of class Gammaproteobacteria (including Enterobacter, Escherichia,
      Klebsiella and Citrobacter), or members of family Enterococcaceae, which are
      often pathogens isolated from bloodstream infections in critically ill patients.
      We also found that antipsychotic treatment, usually associated with an increase
      in body mass index, was marked by a decreased ratio of Bacteroidetes:Firmicutes
      in the gut microbiome, resembling trends seen in obese patients. CONCLUSIONS: Non
      antibiotic prescription drugs have a notable impact on the overall architecture
      of the intestinal microbiome. Further explorations should seek to define
      biomarkers of dysbiosis induced by specific drugs, and potentially tailor live
      biotherapeutics to counter this drug-induced dysbiosis. Many other frequently
      prescribed drugs should also be investigated to better understand the link
      between these drugs, the microbiome and health status.

PMID- 29205416
TI  - The short-term incidence of hepatocellular carcinoma is not increased after
      hepatitis C treatment with direct-acting antivirals: An ERCHIVES study.
AB  - : Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in
      individuals treated with direct-acting antivirals (DAAs). However, making
      definitive conclusions has been challenging because of the heterogeneous
      populations and methodologies of these reports. We investigated whether DAA use
      is associated with higher rates of incident HCC compared to treatment with
      interferon (IFN)-based regimens. We performed a retrospective, population-based
      cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans
      (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological
      response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups,
      respectively. Among all treated persons, risk of HCC was not higher in the DAA
      group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval,
      0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC
      incidence rate nor HCC-free survival were significantly different in the DAA
      group compared to the IFN group (21.2 vs. 22.8 per 1,000 person-years; P = 0.78
      and log-rank P = 0.17, respectively). Untreated persons with cirrhosis had a
      significantly higher HCC incidence rate (45.3 per 1,000 person-years) compared to
      those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons
      had significantly lower probability of HCC development compared to untreated
      persons (log-rank, P = 0.0004). CONCLUSION: DAA treatment is not associated with
      a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the
      short term. Previously reported higher rates of HCC associated with DAA treatment
      may be explained by both the presence of relatively fewer baseline HCC risk
      factors in persons treated with IFN as well as selection bias, given that DAA
      regimens were used to treat persons at higher risk for developing HCC.
      (Hepatology 2018;67:2244-2253).

PMID- 29205417
TI  - Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series
      of substituted glycol ethers.
AB  - A 24 hour in vitro Xenopus oocyte maturation (germinal vesicle breakdown [GVBD])
      assay developed by Pickford and Morris (Environmental Health Perspectives, 1999,
      107, 285-292) was used to screen a series of substituted glycol ethers (GEs).
      Substituted GEs included: ethylene glycol monomethyl ether (EGME); EG monoethyl
      ether (EGEE); EG monopropyl ether (EGPE); EG monobutyl ether (EGBE); EG monohexyl
      ether (EGHE); diethylene glycol monomethyl ether (DGME); triethylene glycol
      monomethyl ether (TGME); ethylene glycol monophenyl ether (EGPhE); EG monobenzyl
      ether (EGBeE); EG diphenyl ether (EGDPhE); and propylene glycol monophenyl ether
      (PGPhE). The GEs inhibited progesterone- or androstenedione-induced GVBD with the
      following relative potency: EGPhE > PGPhE > EGME >> EGEE >= EGBeE > EGPE >> EGBE
      >EGHE > EGDPhE >> DGME >= TGME, or EGPhE >> PGPhE >> EGBeE > EGDPhE > EGEE > EGME
      > EGPE > EGBE, EGHE, DGME and TGME, respectively. Further, [3 H]progesterone or
      [3 H]androstenedione binding affinities to the oocyte plasma membrane
      progesterone receptor (OMPR) or classical androgen receptor (AR) were: EGME >
      EGPhE >= PGPhE >= EGEE > EGBeE >> EGPE >> EGBE >= EGHE > EGDPhE, TGME, and DGME,
      or EGPhE > PGPhE >> EGBeE > EGDPhE >> EGEE >= EGME >> EGPE, EGBE, and EGHE > DGME
      and TGME, respectively. Binary joint mixture studies with the GVBD model using
      flutamide (AR antagonist) and EGPhE indicated that flutamide/EGPhE mixture acted
      in a concentration additive manner. The effects of substituted GE series,
      however, may be mediated through the OMPR; the potency of EGPhE may be the result
      of bimodal inhibition of both the OMPR and AR pathways.

PMID- 29205419
TI  - Community pharmacists-Leaders for antibiotic stewardship in respiratory tract
      infection.
AB  - WHAT IS KNOWN AND OBJECTIVE: Hospital-based pharmacists are established
      antibiotic stewards, but the potential for community pharmacists is largely
      untapped. This commentary explores the potential leadership role of the community
      pharmacist in antibiotic stewardship using upper respiratory tract infection
      (URTI) as an example. COMMENT: Community pharmacists are well placed for
      antibiotic stewardship, possessing the capability (knowledge of medicines),
      opportunity (contact with prescribers and patients) and inherent commitment.
      Providing further motivation with information on patient education has great
      potential to change patient behaviour with respect to consulting a healthcare
      professional for an antibiotic prescription. A Global Respiratory Infection
      Partnership pharmacy-led educational initiative was shown to have a positive
      impact and can promote appropriate self-management of URTI and reduce levels of
      inappropriate antibiotic use. WHAT IS NEW AND CONCLUSION: Community pharmacists
      are ideally placed as antibiotic stewards to lead the quest to contain the threat
      of antibiotic resistance.

PMID- 29205418
TI  - Transcriptional regulation of acetyl CoA and lipid synthesis by PII protein in
      Synechococcus PCC 7942.
AB  - PII protein family is widespread in prokaryotes and plants. In this study,
      impacts of PII deficiency on the synthesis of acetyl CoA and acetyl CoA
      carboxylase enzyme (ACCase) was analyzed in the Synechococcus sp. PCC 7942 by
      evaluating the mRNA levels of pyruvate kinase (PK), pyruvate dehydrogenase (PDH),
      citrate synthase (CS), biotin synthase (BS), biotin carboxylase (BC), biotin
      carboxyl carrier protein (BCCP), carboxyl transferase (CT) alpha and beta
      subunits. The PII deficient Synechococcus sp. PCC 7942 showed upregulation of all
      the above-mentioned genes, except CS. Analyses of genes required for acetyl coA
      synthesis exhibited a substantial increase in the transcript levels of PK and PDH
      in the PII mutant strain. In addition, the PII mutant also displayed reduced
      acetyl CoA content, high ACCase activity, and increased lipid content. The
      lessening of acetyl CoA content was attributed to the rapid utilization of acetyl
      CoA in fatty acid synthesis as well as in the TCA cycle whereas the increased
      ACCase activity was ascribed to the rise in mRNA levels of BS, BC, BCCP, CT
      alpha, and beta genes. However, increased lipid content was correlated with the
      declined total protein content. Hence, the study suggested that PII protein
      regulates the synthesis of acetyl CoA and ACCase enzyme at the transcriptional
      level.

PMID- 29205420
TI  - Ca2+ -Dependent Hyperpolarization Pathways in Sleep Homeostasis and Mental
      Disorders.
AB  - Although we are beginning to understand the neuronal and biochemical nature of
      sleep regulation, questions remain about how sleep is homeostatically regulated.
      Beyond its importance in basic physiology, understanding sleep may also shed
      light on psychiatric and neurodevelopmental disorders. Recent genetic studies in
      mammals revealed several non-secretory proteins that determine sleep duration.
      Interestingly, genes identified in these studies are closely related to
      psychiatric and neurodevelopmental disorders, suggesting that the sleep-wake
      cycle shares some common mechanisms with these disorders. Here we review recent
      sleep studies, including reverse and forward genetic studies, from the
      perspectives of sleep duration and homeostasis. We then introduce a recent
      hypothesis for mammalian sleep in which the fast and slow Ca2+ -dependent
      hyperpolarization pathways are pivotal in generating the SWS firing pattern and
      regulating sleep homeostasis, respectively. Finally, we propose that these
      intracellular pathways are potential therapeutic targets for achieving
      depolarization/hyperpolarization (D/H) balance in psychiatric and
      neurodevelopmental disorders.

PMID- 29205421
TI  - Systematic review with network meta-analysis: comparative assessment of
      tofacitinib and biological therapies for moderate-to-severe ulcerative colitis.
AB  - BACKGROUND: Biological therapies have improved the care of patients with
      ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase
      inhibitor, is potentially a new treatment option. AIM: To comparatively assess
      efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab
      and vedolizumab) in adult patients not previously exposed to TNF antagonists.
      METHODS: We performed a comprehensive search of PubMed, Embase, Scopus, clinical
      trial registries, regulatory authorities' websites and major conference
      proceedings, through August 2017, to identify randomised, placebo-controlled or
      head-to-head trials assessing tofacitinib or biologics as induction and/or
      maintenance therapy in moderate-to-severe UC. Two reviewers independently
      extracted study data and outcomes, and investigated each trial's risk-of-bias. We
      used conventional meta-analysis to synthesise direct evidence, and network meta
      analysis for adjusted indirect treatment comparisons. RESULTS: Fifteen
      randomised, double-blind, placebo-controlled trials (n = 3130) contributed data
      for induction: All treatments are superior to placebo. Indirect treatment
      comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI:
      1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than
      adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab
      (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect
      comparisons between tofacitinib and biologics reached statistical significance.
      Nine studies (n = 1776) contributed maintenance data showing that all treatments
      have higher clinical efficacy than placebo. Safety analyses indicated no
      increased rates of adverse events for the treatments under evaluation (except for
      infliximab), while vedolizumab may have an advantage regarding the occurrence of
      serious adverse events. CONCLUSIONS: Tofacitinib and biologics are efficacious
      and safe for UC. Further high-quality research is warranted to establish the best
      therapeutic option.

PMID- 29205422
TI  - Systematic review: ileoanal pouch microbiota in health and disease.
AB  - BACKGROUND: The resident gut microbiota is essential for physiological processes;
      the disturbance of its balance is linked to intestinal inflammation. The ileoanal
      pouch is a model for the study of intestinal inflammation, as inflammation of the
      pouch is common and mostly develops within 12 months following ileostomy closure.
      This allows the longitudinal study of the microbiota, giving insight into the
      microbiota changes during transition from a normal to an inflamed pouch. AIM: To
      explore the literature on the microbiota of the ileoanal pouch in health and
      disease. METHODS: A systematic computer search of the on-line bibliographic
      databases MEDLINE and EMBASE was performed between 1966 and February 2017.
      Randomised controlled trials, cohort studies and observational studies were
      included. Studies were included if they reported microbiota analysis on faecal
      samples or tissue from the ileoanal pouch. RESULTS: Twenty-six papers were
      eligible. Following ileostomy closure, anaerobic bacteria are the abundant
      species in the ileoanal pouch with presence of a diverse microbiota key to
      maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an
      increase in Clostridia species, while chronic pouchitis is associated with an
      increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in
      Clostridia species appears to be associated with treatment response. CONCLUSION:
      The microbiota plays an important role in both the inflamed and the healthy
      ileoanal pouch. A direct causal relationship between individual microbiota
      changes and inflammation has not yet been established, but manipulation of the
      ileoanal pouch microbiota may be a novel therapeutic avenue to explore.

PMID- 29205423
TI  - Different games of moral bioenhancement.
AB  - Rakic has serious misgivings about Wiseman's inability to frame ethical issues in
      the context of transcending existing realities (the 'is') with the aim of
      achieving what we believe is morally right (the 'ought'). This inability to think
      beyond the present is misguided in ethics. He also criticizes Wiseman for making
      the unimaginative and unsubstantiated assumption that moral bioenhancement (MBE)
      technologies have reached their zenith already. Rakic argues that MBE will become
      more effective in the time to come, that it ought to be optional for every free
      individual, and that it should be directed at enhancing our motivation to act in
      line with how we believe we ought to act. He concedes however that the
      enhancement of our motivation to act morally can only be effective in a limited
      number of morally unambiguous cases. In response, Wiseman argues that Rakic's
      reflections epitomize a way of articulating MBE that is unhelpful, misguidedly
      optimistic, and missing the most important things needing discussion. Such
      reflections are based on inappropriate metaphors, a too future-oriented view
      detached from basic realities, and a false sense of what is possible on the
      global level should MBE be applied. Such ways of thinking about MBE are misguided
      from the outset, and indicative of the enthusiasm for a discourse in need of
      realignment. This should take the form of a more modest, synergistic outlook
      acutely aware of the inexorable limitations imposed on MBE by the internal
      complexity of moral goods, human agents, and the contexts in which moral action
      occurs.

PMID- 29205424
TI  - Multi-source surveillance for work-related crushing injuries.
AB  - BACKGROUND: Work-related crushing injuries are serious but preventable. For 2013
      through 2015, the U.S. Bureau of Labor Statistics' (BLS) Survey of Occupational
      Injuries and Illnesses (SOII) reported 1260 crushing injuries in Michigan. In
      2013, Michigan initiated multi-data source surveillance of work-related crushing
      injuries. METHODS: Records from all 134 of Michigan's hospitals/emergency
      departments (EDs), the Workers Compensation Agency (WCA) and Michigan's Fatality
      Assessment Control and Evaluation (MIFACE) program were used to identify work
      related crushing injuries. Companies, where individuals were hospitalized or had
      an ED visit for a crushing injury, potentially had an OSHA enforcement inspection
      conducted. RESULTS: From 2013 through 2015, there were 3137 work-related crushing
      injury incidents, including two fatalities. The Michigan OSHA program completed
      inspections at 77 worksites identified by the surveillance system. CONCLUSION:
      The Michigan multisource surveillance system identified two and a half times more
      crushing injuries than BLS and was useful for initiating case-based enforcement
      inspections.

PMID- 29205425
TI  - A weighted combined effect measure for the analysis of a composite time-to-first
      event endpoint with components of different clinical relevance.
AB  - Composite endpoints combine several events within a single variable, which
      increases the number of expected events and is thereby meant to increase the
      power. However, the interpretation of results can be difficult as the observed
      effect for the composite does not necessarily reflect the effects for the
      components, which may be of different magnitude or even point in adverse
      directions. Moreover, in clinical applications, the event types are often of
      different clinical relevance, which also complicates the interpretation of the
      composite effect. The common effect measure for composite endpoints is the all
      cause hazard ratio, which gives equal weight to all events irrespective of their
      type and clinical relevance. Thereby, the all-cause hazard within each group is
      given by the sum of the cause-specific hazards corresponding to the individual
      components. A natural extension of the standard all-cause hazard ratio can be
      defined by a "weighted all-cause hazard ratio" where the individual hazards for
      each component are multiplied with predefined relevance weighting factors. For
      the special case of equal weights across the components, the weighted all-cause
      hazard ratio then corresponds to the standard all-cause hazard ratio. To identify
      the cause-specific hazard of the individual components, any parametric survival
      model might be applied. The new weighted effect measure can be tested for
      deviations from the null hypothesis by means of a permutation test. In this work,
      we systematically compare the new weighted approach to the standard all-cause
      hazard ratio by theoretical considerations, Monte-Carlo simulations, and by means
      of a real clinical trial example.

PMID- 29205426
TI  - Systematic review with meta-analysis: thiopurines decrease the risk of colorectal
      neoplasia in patients with inflammatory bowel disease.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk of
      developing colorectal neoplasia. AIM: To investigate whether thiopurines can
      decrease the risk of developing colorectal neoplasia in patients with ulcerative
      colitis (UC) or Crohn's disease (CD). METHODS: We conducted a meta-analysis of 24
      observational studies involving 76,999 participants to evaluate the risks of
      developing colorectal neoplasia in IBD patients receiving thiopurine treatment.
      Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the risks of
      colorectal neoplasia were calculated using a random-effects model. RESULTS: The
      overall pooled estimate revealed a protective effect of thiopurine use on
      colorectal neoplasia in patients with IBD (OR = 0.63, 95% CI 0.46-0.86). The
      effect was significant in UC patients (OR = 0.67, 95% CI 0.45-0.98), but was not
      significant in CD patients (OR = 1.06, 95% CI 0.54-2.09). Thiopurines exposure
      significantly decreased the risk of colorectal cancer (CRC) (OR = 0.65, 95% CI
      0.45-0.96) and advanced colorectal neoplasia (CRC and/or high-grade dysplasia)
      (OR = 0.62, 95% CI 0.44-0.89), but did not decrease the risk of dysplasia alone
      (OR = 0.90, 95% CI 0.37-2.21). Tendencies towards the protective effect of
      thiopurines were distinct in clinic-based studies (OR = 0.59, 95% CI 0.42-0.82)
      and case-control studies (OR = 0.40, 95% CI 0.26-0.62), but not in population
      based studies (OR = 0.95, 95% CI 0.55-1.62) and cohort studies (OR = 0.98, 95% CI
      0.81-1.18). Interestingly, studies conducted in Europe (OR = 0.48, 95% CI 0.31
      0.77), rather than in North America (OR = 0.91, 95% CI 0.67-1.24), showed the
      protective effect of thiopurines. CONCLUSIONS: This meta-analysis revealed an
      antineoplastic effect of thiopurines on colorectal neoplasia in patients with
      IBD, particularly amongst patients with UC.

PMID- 29205427
TI  - Reply.

PMID- 29205428
TI  - Power Doppler Ultrasonography and Shear Wave Elastography as Complementary
      Imaging Methods for Suspected Local Breast Cancer Recurrence.
AB  - OBJECTIVES: To prospectively investigate the diagnostic accuracy and clinical
      consequences of power Doppler morphologic criteria and shear wave elastography
      (SWE) as complementary imaging methods for evaluation of suspected local breast
      cancer recurrence in the ipsilateral breast or chest wall. METHODS: Thirty-two
      breast masses with a suspicion of local breast cancer recurrence on B-mode
      ultrasonography underwent complementary power Doppler and SWE evaluations. Power
      Doppler morphologic criteria were classified as avascular, hypovascular, or
      hypervascular. Shear wave elastography was classified according to a 5-point
      scale (SWE score) and SWE maximum elasticity. Diagnostic accuracy was assessed by
      the sensitivity, specificity, and area under the curve. A decision curve analysis
      assessed clinical consequences of each method. The reference standard for
      diagnosis was defined as core needle or excisional biopsy. RESULTS:
      Histopathologic examinations revealed 9 (28.2%) benign and 23 (71.8%) malignant
      cases. Power Doppler ultrasonography (US) had sensitivity of 34.8% (95%
      confidence interval [CI], 6.6%-62.9%) and specificity of 45.4% (95% CI, 19.3%
      71.5%). The SWE score (>=3) had sensitivity of 87.0% (95% CI, 66.4%-97.2%) and
      specificity of 44.4% (95% CI, 13.7%-78.8%). The SWE maximum elasticity (velocity
      > 6.5cm/s) had sensitivity of 87% (95% CI, 66.4%-97.2%) and specificity of 77.8%
      (95% CI, 40.0% to 97.2%). The areas under the curves for the SWE score and SWE
      maximum elasticity were 0.71 (95% CI, 0.53-0.87) and 0.82 (95% CI, 0.64-0.93),
      respectively (P = .32). CONCLUSIONS: Power Doppler US is unsuitable for
      discrimination between local breast cancer recurrence and fibrosis. Although the
      SWE score and SWE maximum elasticity can make this discrimination, the use of
      these methods to determine biopsy may lead to poorer clinical outcomes than the
      current practice of performing biopsies of all suspicious masses.

PMID- 29205429
TI  - Erratum.

PMID- 29205430
TI  - Erratum.

PMID- 29205431
TI  - Anatomic Delineation of Tarsal Tunnel Innervation via Ultrasonography.
AB  - OBJECTIVES: High-resolution ultrasonography (US) can play an important role in
      studying nerves, as it has several advantages. Entrapments of distal tibial nerve
      branches can be mapped out or diagnosed with selective anesthetic blocks, and US
      can guide therapeutic procedures, such as radiofrequency ablation and selective
      infiltrations of specific nerve branches. The aim of this study was to verify
      that US is an effective method for accurately locating the posterior tibial nerve
      and its terminal branches, such as the medial calcaneal branch, the first
      calcaneal branch, and the medial and lateral plantar nerves. METHODS: In this
      study, we analyzed the correlation between US mapping and real anatomy after
      cadaveric dissection, assessing the distribution and variability of the tibial
      nerve and its terminal branches. We used 12 fresh anatomic specimens of the foot
      and ankle, including the calf. A high-resolution US study of the tibial nerve and
      its branches was performed. RESULTS: The results of the US studies of the
      anatomic specimens were drawn as paper diagrams and in data collection tables.
      Both were completed twice per anatomic specimen, first using the results of the
      US study and second using the results from dissection of the anatomic specimens;
      this approach enabled us to compare the results and verify whether the US study
      and the dissection correlated on the topography of the tibial nerve and its
      terminal branches. We found almost total agreement between the US and dissection
      results, with no significant differences between the evaluations. CONCLUSIONS: On
      the basis of this work, we can conclude that high-resolution US is almost 100%
      effective as a tool for identifying the tibial nerve and its branches, enabling
      the specialist to make diagnoses or perform selective treatments on each nerve
      branch and even to design surgical interventions by observing the patient's
      anatomy before performing the dissection.

PMID- 29205432
TI  - Sofosbuvir and daclatasvir therapy in patients with hepatitis C-related advanced
      decompensated liver disease (MELD >= 15).
AB  - BACKGROUND: Antiviral therapy for hepatitis C has the potential to improve liver
      function in patients with decompensated cirrhosis. AIMS: To examine the
      virological response and effect of viral clearance in patients with decompensated
      hepatitis C cirrhosis all with MELD scores >=15 following sofosbuvir/daclatasvir
      +/- ribavirin. METHODS: We prospectively collected data on patients who commenced
      sofosbuvir/daclatasvir for 24-weeks under the Australian patient supply program
      (TOSCAR) and analysed outcomes including sustained viral response at 12 weeks
      (SVR12), death and transplant. RESULTS: 108 patients (M/F, 79/29; median age
      56years; Child-Pugh 10; MELD 16; genotype 1/3, 55/47) received
      sofosbuvir/daclatasvir and two also received ribavirin. On intention-to-treat,
      the SVR12 rate was 70% (76/108). Seventy-eight patients completed 24-weeks
      therapy. SVR12 was achieved in 56 of these patients on per-protocol-analysis
      (76%). SVR12 was 80% in genotype 1 compared to 69% in genotype 3. Thirty patients
      failed to complete therapy. In patients achieving SVR12, median MELD and Child
      Pugh fell from 16(IQR15-17) to 14(12-17) and 10(9-11) to 8(7-9), respectively
      (P<.001). In those who died, MELD increased from 16 to 23 at death (P=.036).
      Patients who required transplantation had a significantly higher baseline MELD
      (20) compared to those patients completing treatment (16) (P=.0010). The odds
      ratio for transplant in patients with baseline MELD >=20 was 13.8(95%CI 2.78
      69.04). CONCLUSIONS: SVR12 rates with sofosbuvir/daclatasvir in advanced liver
      disease are lower than in compensated disease. Although treatment improves MELD
      and Child-Pugh in most patients, a significant proportion will die or require
      transplantation. In those with MELD >=20, it may be better to delay treatment
      until post-transplant.

PMID- 29205433
TI  - Faculty feedback that begins with resident self-assessment: motivation is the key
      to success.
AB  - CONTEXT: The seeking and incorporating of feedback are necessary for continuous
      performance improvement in medicine. We know that beginning feedback
      conversations with resident self-assessment may reduce some of the tensions
      experienced by faculty staff. However, we do not fully understand how residents
      experience feedback that begins with self-assessment, and whether any existing
      theoretical frameworks can explain their experiences. METHODS: We conducted a
      constructivist grounded theory study exploring physical medicine and
      rehabilitation residents' experiences as they engaged in a structured self
      assessment and faculty staff feedback programme. Utilising purposive sampling, we
      conducted 15 individual interviews and analysed verbatim transcripts iteratively.
      We implemented several procedures to enhance the credibility of the findings and
      the protection of participants during recruitment, data collection and data
      analysis. After defining the themes, we reviewed a variety of existing frameworks
      to determine if any fitted the data. RESULTS: Residents valued self-assessment
      followed by feedback (SAFF) and had clear ideas of what makes the process useful.
      Time pressures and poor feedback quality could lead to a process of 'just going
      through the motions'. Motivation coloured residents' experiences, with more
      internalised motivation related to a more positive experience. There were no
      gender- or year of training-related patterns. CONCLUSIONS: Self-determination
      theory provided the clearest lens for framing our findings and fitted into a
      conceptual model linking the quality of the SAFF experience and residents'
      motivational loci. We identified several study limitations including time in the
      field, evolving characteristics of the SAFF programme and the absence of faculty
      voices. We believe that by better understanding residents' experiences of SAFF,
      educators may be able to tailor the feedback process, enhance clinical
      performance and ultimately improve patient care.

PMID- 29205434
TI  - Bayesian inference for unidirectional misclassification of a binary response
      trait.
AB  - When assessing association between a binary trait and some covariates, the binary
      response may be subject to unidirectional misclassification. Unidirectional
      misclassification can occur when revealing a particular level of the trait is
      associated with a type of cost, such as a social desirability or financial cost.
      The feasibility of addressing misclassification is commonly obscured by model
      identification issues. The current paper attempts to study the efficacy of
      inference when the binary response variable is subject to unidirectional
      misclassification. From a theoretical perspective, we demonstrate that the key
      model parameters possess identifiability, except for the case with a single
      binary covariate. From a practical standpoint, the logistic model with
      quantitative covariates can be weakly identified, in the sense that the Fisher
      information matrix may be near singular. This can make learning some parameters
      difficult under certain parameter settings, even with quite large samples. In
      other cases, the stronger identification enables the model to provide more
      effective adjustment for unidirectional misclassification. An extension to the
      Poisson approximation of the binomial model reveals the identifiability of the
      Poisson and zero-inflated Poisson models. For fully identified models, the
      proposed method adjusts for misclassification based on learning from data. For
      binary models where there is difficulty in identification, the method is useful
      for sensitivity analyses on the potential impact from unidirectional
      misclassification.

PMID- 29205435
TI  - Relative efficiency of precision medicine designs for clinical trials with
      predictive biomarkers.
AB  - Prospective randomized clinical trials addressing biomarkers are time consuming
      and costly, but are necessary for regulatory agencies to approve new therapies
      with predictive biomarkers. For this reason, recently, there have been many
      discussions and proposals of various trial designs and comparisons of their
      efficiency in the literature. We compare statistical efficiencies between the
      marker-stratified design and the marker-based precision medicine design regarding
      testing/estimating 4 hypotheses/parameters of clinical interest, namely,
      treatment effects in each marker-positive and marker-negative cohorts, marker-by
      treatment interaction, and the marker's clinical utility. As may be expected, the
      stratified design is more efficient than the precision medicine design. However,
      it is perhaps surprising to find out how low the relative efficiency can be for
      the precision medicine design. We quantify the relative efficiency as a function
      of design factors including the marker-positive prevalence rate, marker assay and
      classification sensitivity and specificity, and the treatment randomization
      ratio. It is interesting to examine the trends of the relative efficiency with
      these design parameters in testing different hypotheses. We advocate to use the
      stratified design over the precision medicine design in clinical trials with
      predictive biomarkers.

PMID- 29205436
TI  - Validation of the Pain Resilience Scale in Chinese-speaking patients with
      temporomandibular disorders pain.
AB  - To validate the Pain Resilience Scale (PRS) for use in Chinese patients with
      temporomandibular disorders (TMD) pain. According to international guidelines,
      the original PRS was first translated and cross-culturally adapted to formulate
      the Chinese version of PRS (PRS-C). A total of 152 patients with TMD pain were
      recruited to complete series of questionnaires. Reliability of the PRS-C was
      investigated using internal consistency and test-retest reliability. Validity of
      the PRS-C was calculated using cross-cultural validity and convergent validity.
      Cross-cultural validity was evaluated by examining the confirmatory factor
      analysis (CFA). And convergent validity was examined through correlating the PRS
      C scores with scores of 2 commonly used pain-related measures (the Connor
      Davidson Resilience Scale [CD-RISC] and the Tampa Scale for Kinesiophobia for
      Temporomandibular Disorders [TSK-TMD]). The PRS-C had a high internal consistency
      (Cronbach's alpha = 0.92) and good test-retest reliability (intra-class
      correlation coefficient [ICC] = 0.81). The CFA supported a 2-factor model for the
      PRS-C with acceptable fit to the data. The fit indices were chi-square/DF = 2.21,
      GFI = 0.91, TLI = 0.97, CFI = 0.98 and RMSEA = 0.08. As regards convergent
      validity, the PRS-C evidenced moderate-to-good relationships with the CD-RISC and
      the TSK-TMD. The PRS-C shows good psychometric properties and could be considered
      as a reliable and valid measure to evaluate pain-related resilience in patients
      with TMD pain.

PMID- 29205437
TI  - mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.
AB  - Messenger RNA is a flexible tool box that plays a key role in the dynamic
      regulation of gene expression. RNA modifications variegate the message conveyed
      by the mRNA. Similar to DNA and histone modifications, mRNA modifications are
      reversible and play a key role in the regulation of molecular events. Our
      understanding about the landscape of RNA modifications is still rudimentary in
      contrast to DNA and histone modifications. The major obstacle has been the lack
      of sensitive detection methods since they are non-editing events. However, with
      the advent of next-generation sequencing techniques, RNA modifications are being
      identified precisely at single nucleotide resolution. In recent years,
      methylation at the N6 position of adenine (m6 A) has gained the attention of RNA
      biologists. The m6 A modification has a set of writers (methylases), erasers
      (demethylases), and readers. Here, we provide a summary of interesting facts,
      conflicting findings, and recent advances in the technical and functional aspects
      of the m6 A epitranscriptome.

PMID- 29205438
TI  - Towards the identification of reliable sperm biomarkers for male infertility: A
      sperm proteomic approach.
AB  - Male infertility evaluation is mainly based on semen analysis. Thus,
      identification of additional diagnostic methods is valuable. The aim of this
      study was to analyse the sperm proteome of infertile men to identify the
      underlying mechanisms and reliable diagnostic biomarkers. This cross-sectional
      study consisted of 16 infertile men and seven proven fertile men. An LC-MS/MS
      approach was performed in five pooled samples of each group (proven fertile men,
      primary infertility and secondary infertility). Differentially expressed proteins
      were used for functional enrichment analyses, and the most central proteins
      involved in altered functions in both infertile groups and the testis-specific
      proteins were validated using Western blotting and immunocytochemistry. In total,
      1,305 sperm proteins were identified, of which 102 were underexpressed and 15
      were overexpressed proteins in both infertile groups. Underexpressed proteins
      were mostly related to protein post-translational modification and folding,
      especially BAG6, HSPA2 and SPA17. Validation analysis revealed an underexpression
      of BAG6 in infertile men, whereas HSPA2 and SPA17 expressions did not differ
      between the groups. No differences were observed in the sperm localisation of
      these proteins. An overexpression of HIST1H2BA-a testis-specific protein-was
      observed in both proteomic approaches. Therefore, BAG6 and HIST1H2BA are
      potential candidates for male infertility biomarkers.

PMID- 29205439
TI  - Influence of removable prostheses on mastication in elderly subjects with
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a prevalent disease in the elderly population, and
      it may affect the temporomandibular joint (TMJ) and the stomatognathic system.
      This study evaluated masticatory function in elderly patients with RA before and
      after oral rehabilitation with removable prostheses. Forty-five elders with
      partial or total edentulism who were using unsatisfactory removable prostheses
      were selected and assigned to 3 groups: RA with TMJ involvement, RA without TMJ
      involvement and healthy controls. Masticatory function was assessed in terms of
      masticatory performance (MP) and maximum bite force (MBF). The former was
      determined by the sieving method, and the latter was measured by pressure sensors
      placed in the bilateral molar regions. The variables were first evaluated in
      elderly subjects wearing unsatisfactory prostheses and re-assessed after
      participants had received new removable prostheses. Comparisons between groups
      and among time points were performed with analysis of variance for repeated
      measures and the Tukey-Kramer test (P < .05). Comparison among groups showed
      decreased MP in elders with RA before new prosthesis insertion (P < .05).
      Irrespective of TMJ involvement, MP improved after treatment in subjects with RA.
      Rheumatoid arthritis groups also showed decreased MBF (P < .05), which improved
      after new prosthesis insertion. Rheumatoid arthritis might impair masticatory
      function, and well-fitted removable prosthesis insertion might be very beneficial
      in elders with RA.

PMID- 29205440
TI  - Effect of reflection on medical students' situational interest: an experimental
      study.
AB  - CONTEXT: Reflection has been considered crucial to learning. Engaging in
      reflection while solving problems is expected to foster identification of
      knowledge gaps and interest in learning more about them, the latter being a major
      motivational force in learning. Although theoretically sound, this assumption
      still lacks empirical evidence. This experiment investigated whether reflection
      while diagnosing clinical cases of different levels of difficulty influences
      medical students' awareness of knowledge gaps and situational interest. METHODS:
      Forty-two fourth-year students from a Brazilian medical school were randomly
      allocated to diagnose six clinical cases (three difficult; three easy), either by
      following a structured reflection procedure (reflection group) or by giving
      alternative diagnoses (control group). Subsequently, for each case, all students
      rated their situational interest and awareness of knowledge gaps. RESULTS:
      Situational interest was significantly higher in the reflection group than in the
      control group (mean = 4.10, standard deviation = 0.50 versus mean = 3.65,
      standard deviation = 0.48, respectively; p = 0.003; range, 1-5). The effect size
      was large (d = 0.92). Awareness of knowledge gaps was higher in the reflection
      group than in the control group, but the difference was not significant. Case
      difficulty influenced both situational interest, which was significantly higher
      on easy than on difficult cases (mean = 3.96, standard deviation = 0.56 versus
      mean = 3.80, standard deviation = 0.55, respectively; p = 0.004), and awareness
      of knowledge gaps, with higher scores observed on difficult compared with easy
      cases (mean = 3.99, standard deviation = 0.46 versus mean = 3.66, standard
      deviation = 0.53, respectively; p < .001). No interaction between experimental
      condition and case difficulty emerged. CONCLUSION: Relative to providing
      alternative diagnoses while solving cases, structured reflection increased
      medical students' interest and may therefore be a useful tool for teachers
      concerned with enhancing students' motivation for learning. Surprisingly, easy
      cases promoted higher situational interest despite the higher awareness of
      knowledge gaps on difficult cases. This suggests the potential for case
      difficulty to inhibit students' interest in learning, a possibility that demands
      further investigation.

PMID- 29205441
TI  - Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C
      liver transplant recipients.
AB  - : Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of
      intravenous drug use have led to an increase in the number of organ donors who
      are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of
      HCV transmission from the liver grafts of these donors to recipients is unknown.
      To estimate the incidence of HCV transmission, we prospectively followed 26
      consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant
      recipients who received a liver graft from donors who were HCV antibody-positive
      but serum NAT-negative between March 2016 and March 2017. HCV transmission was
      considered to have occurred if recipients exhibited a positive HCV PCR test by 3
      months following transplantation. Drug overdose was listed as the cause of death
      in 15 (60%) of the donors. One recipient died 18 days after transplantation from
      primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV
      transmission occurred in 4 (16%), at a median follow-up of 11 months, all from
      donors who died of drug overdose. Three of these patients were treated with
      direct-acting antiviral therapy, with two achieving a sustained virologic
      response and one an end-of-treatment response. One patient with HCV transmission
      died after a complicated postoperative course and did not receive antiviral
      therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients
      receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of
      HCV transmission was 16%, with the highest risk conferred by donors who died of
      drug overdose; given the availability of safe and highly effective antiviral
      therapies, use of such organs could be considered to expand the donor pool.
      (Hepatology 2018;67:1673-1682).

PMID- 29205442
TI  - Palliative care for end-of-life patients in a basic emergency service.
AB  - This research sought to describe the care provided by the nursing staff of the
      Western Department of the Basic Emergency Service for end-of-life patients. This
      was a retrospective, quantitative, exploratory and descriptive (level I) study,
      which sought to research the nursing records of 83 patients from admission to
      death. Patients who met the following inclusion criteria were considered
      eligible: adults; had an oncological or nononcological, advanced and irreversible
      chronic disease; and died in the Basic Emergency Service in the period from
      January 2011 to December 2012. An instrument was created for data collection, the
      content, relevance and adequacy of which was validated by a panel of experts in
      the area of palliative care. The study protocol was approved by the Institutional
      Ethics Committee. The main results indicate that the majority of patients died in
      the Observation Room in a period between the first two and twenty-four hours.
      Nursing interventions favoured technical-instrumental care related to medical
      prescriptions and service routines such as venous punctures, catheterisations,
      taking blood samples for analysis, aspiration of secretions, intravenous
      administration of fluids and drugs for symptomatic control, and monitoring of
      vital parameters and the state of consciousness. With the proximity of death, the
      nurses favoured the registration of cardiorespiratory arrest, cardiopulmonary
      resuscitation manoeuvres and aspiration of secretions. In the recognition of
      predictive factors of imminent death, the nurses favoured the patient's entry
      into a comatose state and aggravation of asthenia. In most patients, the entry
      into agony phase was not diagnosed.

PMID- 29205443
TI  - Digitised evaluation of speech intelligibility using vowels in maxillectomy
      patients.
AB  - Among the functional disabilities that patients face following maxillectomy,
      speech impairment is a major factor influencing quality of life. Proper
      rehabilitation of speech, which may include prosthodontic and surgical treatments
      and speech therapy, requires accurate evaluation of speech intelligibility (SI).
      A simple, less time-consuming yet accurate evaluation is desirable both for
      maxillectomy patients and the various clinicians providing maxillofacial
      treatment. This study sought to determine the utility of digital acoustic
      analysis of vowels for the prediction of SI in maxillectomy patients, based on a
      comprehensive understanding of speech production in the vocal tract of
      maxillectomy patients and its perception. Speech samples were collected from 33
      male maxillectomy patients (mean age 57.4 years) in two conditions, without and
      with a maxillofacial prosthesis, and formant data for the vowels /a/,/e/,/i/,/o/,
      and /u/ were calculated based on linear predictive coding. The frequency range of
      formant 2 (F2) was determined by differences between the minimum and maximum
      frequency. An SI test was also conducted to reveal the relationship between SI
      score and F2 range. Statistical analyses were applied. F2 range and SI score were
      significantly different between the two conditions without and with a prosthesis
      (both P < .0001). F2 range was significantly correlated with SI score in both the
      conditions (Spearman's r = .843, P < .0001; r = .832, P < .0001, respectively).
      These findings indicate that calculating the F2 range from 5 vowels has clinical
      utility for the prediction of SI after maxillectomy.

PMID- 29205444
TI  - Switching from infliximab innovator to biosimilar in patients with inflammatory
      bowel disease: a 12-month multicentre observational prospective cohort study.
AB  - BACKGROUND: Infliximab biosimilars have become available for treatment of
      inflammatory bowel disease (IBD). However, data showing long-term safety and
      effectiveness of biosimilars in IBD patients are limited. AIM: To study
      prospectively the switch from infliximab innovator to biosimilar in an IBD cohort
      with 12 months follow-up to evaluate safety and effectiveness. METHODS: Adult IBD
      patients from two hospitals treated with infliximab innovator (Remicade; Janssen
      Biotech,  Horsham ,  Pennsylvania, USA) were switched to infliximab biosimilar
      (Inflectra; Hospira, Lake Forest, Illinois, USA) as part of routine care, but in
      a controlled setting. Blood samples were taken just before the first, second,
      fourth and seventh infusion of biosimilar. Infliximab trough levels, antibodies
      to-infliximab (ATI), CRP and ESR were measured and disease activity scores were
      calculated. RESULTS: Our cohort consisted of 133 IBD patients (64% CD, 36% UC).
      Before switching we found widely varying infliximab levels (median 3.5 MUg/mL).
      ATI were detected in eight patients (6%). Most patients were in remission or had
      mild disease (CD: 82% UC: 90%). After switching to biosimilar, 35 patients (26%)
      discontinued therapy within 12 months, mostly due to subjective higher disease
      activity (9%) and adverse events (AE, 9.8%). AE included general malaise/fatigue
      (n = 7), arthralgia (n = 2), skin problems (n = 2) and infusion reactions (n =
      2). No differences in IFX levels, CRP, and disease activity scores were found
      between the four time points (P >= .0917). CONCLUSIONS: We found no differences
      in drug levels and disease activity between infliximab innovator and biosimilar
      in our IBD cohort, indicating that biosimilars are safe and effective. The high
      proportions of discontinuers were mostly due to elective withdrawal or subjective
      disease worsening.

PMID- 29205445
TI  - Analysis of the U.S. patient referral network.
AB  - In this paper, we analyze the US Patient Referral Network (also called the Shared
      Patient Network) and various subnetworks for the years 2009 to 2015. In these
      networks, two physicians are linked if a patient encounters both of them within a
      specified time interval, according to the data made available by the Centers for
      Medicare and Medicaid Services. We find power law distributions on most state
      level data as well as a core-periphery structure. On a national and state level,
      we discover a so-called small-world structure as well as a "gravity law" of the
      type found in some large-scale economic networks. Some physicians play the role
      of hubs for interstate referral. Strong correlations between certain network
      statistics with health care system statistics at both the state and national
      levels are discovered. The patterns in the referral network evinced using several
      statistical analyses involving key metrics derived from the network illustrate
      the potential for using network analysis to provide new insights into the health
      care system and opportunities or mechanisms for catalyzing improvements.

PMID- 29205446
TI  - Induced smoothing for rank-based regression with recurrent gap time data.
AB  - Various semiparametric regression models have recently been proposed for the
      analysis of gap times between consecutive recurrent events. Among them, the
      semiparametric accelerated failure time (AFT) model is especially appealing owing
      to its direct interpretation of covariate effects on the gap times. In general,
      estimation of the semiparametric AFT model is challenging because the rank-based
      estimating function is a nonsmooth step function. As a result, solutions to the
      estimating equations do not necessarily exist. Moreover, the popular resampling
      based variance estimation for the AFT model requires solving rank-based
      estimating equations repeatedly and hence can be computationally cumbersome and
      unstable. In this paper, we extend the induced smoothing approach to the AFT
      model for recurrent gap time data. Our proposed smooth estimating function
      permits the application of standard numerical methods for both the regression
      coefficients estimation and the standard error estimation. Large-sample
      properties and an asymptotic variance estimator are provided for the proposed
      method. Simulation studies show that the proposed method outperforms the existing
      nonsmooth rank-based estimating function methods in both point estimation and
      variance estimation. The proposed method is applied to the data analysis of
      repeated hospitalizations for patients in the Danish Psychiatric Center Register.

PMID- 29205447
TI  - Multivariate space-time modelling of multiple air pollutants and their health
      effects accounting for exposure uncertainty.
AB  - The long-term health effects of air pollution are often estimated using a spatio
      temporal ecological areal unit study, but this design leads to the following
      statistical challenges: (1) how to estimate spatially representative pollution
      concentrations for each areal unit; (2) how to allow for the uncertainty in these
      estimated concentrations when estimating their health effects; and (3) how to
      simultaneously estimate the joint effects of multiple correlated pollutants. This
      article proposes a novel 2-stage Bayesian hierarchical model for addressing these
      3 challenges, with inference based on Markov chain Monte Carlo simulation. The
      first stage is a multivariate spatio-temporal fusion model for predicting areal
      level average concentrations of multiple pollutants from both monitored and
      modelled pollution data. The second stage is a spatio-temporal model for
      estimating the health impact of multiple correlated pollutants simultaneously,
      which accounts for the uncertainty in the estimated pollution concentrations. The
      novel methodology is motivated by a new study of the impact of both particulate
      matter and nitrogen dioxide concentrations on respiratory hospital admissions in
      Scotland between 2007 and 2011, and the results suggest that both pollutants
      exhibit substantial and independent health effects.

PMID- 29205448
TI  - Soft Tissue Masses of the Knee Related to a Focal Defect of the Lateral Patellar
      Retinaculum.
AB  - We report on the imaging features of 6 soft tissue masses in the anterolateral
      aspect of the knee related to a focal defect of the lateral patellar retinaculum.
      In 4 patients (3 female and 1 male; 6-65 years) presenting with nontender
      palpable soft tissue masses in the anterolateral aspect of their knees,
      ultrasonography showed a focal defect of the lateral patellar retinaculum with
      herniation of the Hoffa fat pad, which was only visible in flexion. A magnetic
      resonance imaging examination performed in 1 case confirmed the defect in the
      lateral patellar retinaculum but did not show a mass, as the knee was examined
      only at 10 degrees  of flexion. The 2 remaining patients (one male and 1 female;
      62 and 55 years) presented with soft tissue masses in their anterolateral knees
      in both flexion and extension. These masses were related respectively to a lipoma
      of the Hoffa fat pad and to a ganglion cyst, both herniated through a defect of
      the lateral patellar retinaculum. Our cases suggest that a focal defect of the
      lateral patellar retinaculum may be a route for Hoffa fat pad herniation as well
      as a route for superficial extension of infrapatellar fat lesions such as lipomas
      and ganglion cysts.

PMID- 29205449
TI  - The relationship between jaw-opening force and the cross-sectional area of the
      suprahyoid muscles in healthy elderly.
AB  - We conducted a clinical cross-sectional study to examine the relationship between
      jaw-opening force and the cross-sectional area of the suprahyoid muscles and
      whole skeletal muscle mass. Subjects were healthy 39 males and 51 females without
      dysphagia and sarcopenia, aged 65 years and older. Jaw-opening force was measured
      three times using a jaw-opening sthenometer; the maximum of these three was taken
      as the measurement value. The cross-sectional area of the geniohyoid and anterior
      belly of the digastric muscles were evaluated using ultrasonography. The skeletal
      muscle mass index, gait speed and grip strength were evaluated according to the
      diagnostic criteria of the Asian Working Group for Sarcopenia. For each sex, a
      multiple regression analysis determined the factors that affect jaw-opening
      force. Jaw-opening force was associated with the cross-sectional area of the
      geniohyoid muscle in males (regression coefficient [beta] = 0.441, 95% confidence
      interval [CI] = 14.28-56.09) and females (beta = 0.28, 95% CI = 3.10-54.57).
      Furthermore, in females only, jaw-opening force was associated with the skeletal
      muscle mass index (beta = 0.40, 95% CI = 3.67-17.81). In contrast, jaw-opening
      force was not associated with the cross-sectional area of the anterior belly of
      the digastric muscle in either sex. In healthy elderly males and females, jaw
      opening force was positively associated with the cross-sectional area of the
      geniohyoid muscle. However, the jaw-opening force was positively associated with
      the skeletal muscle mass index only in females.

PMID- 29205450
TI  - Clinical relevance of deferasirox trough levels in beta-thalassemia patients.
AB  - We evaluated the role of deferasirox therapeutic drug monitoring in order to
      avoid toxicity or treatment failure. Plasma concentrations, measured between two
      consecutive liver iron determinations, were determined at the end of dosing
      interval. Fifty-four beta-thalassemic adult patients were enrolled: 50% were
      males; median age was 32.3 years (IQR 19.1-41.7 years) and median body mass index
      was 22.25 kg/m2 (IQR 20.24-23.75 kg/m2 ). The mean deferasirox dose was 28.6 +/-
      6.3 mg/kg/d and mean plasma concentration was 17.3 +/- 16.8 MUg/mL. Drug levels
      showed lower results in males. Deferasirox concentration was significantly
      correlated with serum creatinine levels (P = .01) and serum ferritin (P < .0001).
      The assessment of deferasirox therapeutic drug monitoring could help clinicians
      to predict patient responses and to optimize the therapy.

PMID- 29205452
TI  - An R2 -curve for evaluating the accuracy of dynamic predictions.
AB  - In the context of chronic diseases, patient's health evolution is often evaluated
      through the study of longitudinal markers and major clinical events such as
      relapses or death. Dynamic predictions of such types of events may be useful to
      improve patients management all along their follow-up. Dynamic predictions
      consist of predictions that are based on information repeatedly collected over
      time, such as measurements of a biomarker, and that can be updated as soon as new
      information becomes available. Several techniques to derive dynamic predictions
      have already been suggested, and computation of dynamic predictions is becoming
      increasingly popular. In this work, we focus on assessing predictive accuracy of
      dynamic predictions and suggest that using an R2 -curve may help. It facilitates
      the evaluation of the predictive accuracy gain obtained when accumulating
      information on a patient's health profile over time. A nonparametric inverse
      probability of censoring weighted estimator is suggested to deal with censoring.
      Large sample results are provided, and methods to compute confidence intervals
      and bands are derived. A simulation study assesses the finite sample size
      behavior of the inference procedures and illustrates the shape of some R2 -curves
      which can be expected in common settings. A detailed application to kidney
      transplant data is also presented.

PMID- 29205453
TI  - Localization of thrombospondin-1 and its receptor CD36 in the ovary of the
      ostrich (Struthio camelus).
AB  - Angiogenesis, the formation of new blood vessels from pre-existing vasculature,
      plays a decisive role for the rapid growth of avian follicles. Compared to
      mammals, few data on the angiogenesis in the avian ovary are available. However,
      whereas several pro-angiogenic factors in the avian ovary have been recently
      studied in detail, little information is available on the localization of anti
      angiogenic factors. The aim of this study was to determine the localization and
      possible function of the anti-angiogenic factor thrombospondin-1 (TSP-1) and its
      receptor CD36 in the ovary of the ostrich using immunohistochemistry and to
      correlate the results with ultrastructural data. Whereas the oocytes and
      granulosa cells of all follicular stages were negative for TSP-1, myofibroblasts
      of the theca externa and smooth muscle cells of blood vessels showed distinct
      reactions. A distinctly different staining pattern was observed for CD36. The
      oocytes were CD36 negative. No immunostaining for CD36 could be observed neither
      in the granulosa cells nor in the adjacent theca interna of vitellogenic
      follicles. In the theca externa, blood vessels protruding towards the oocyte
      showed CD36-positive endothelial cells. In conclusion, a fine balance between
      angiogenic and anti-angiogenic processes assures that a dense net of blood
      vessels develops during the rapid growth of a selected follicle. Anti-angiogenic
      molecules, such as TSP-1 and its receptor CD36 may, after the oocyte has reached
      its final size, inhibit further angiogenesis and limit the transport of yolk
      material to the mature oocyte. By this mechanism, the growth of the megalecithal
      oocyte during folliculogenesis may cease.

PMID- 29205451
TI  - Subdermal Ultrasound Contrast Agent Injection for Sentinel Lymph Node
      Identification: An Analysis of Safety and Contrast Agent Dose in Healthy
      Volunteers.
AB  - OBJECTIVES: Mapping of the lymphatic chain for identification of the sentinel
      lymph node (SLN) is an important aspect of predicting outcomes for patients with
      breast cancer, and it is usually performed as an intraoperative procedure using
      blue dye and/or radiopharmaceutical agents. Recently, the use of contrast
      enhanced ultrasound (CEUS) has been proposed as an alternative imaging technique
      for this mapping. The objective of this study was to evaluate the use of
      subdermal administration of the ultrasound (US) contrast agent Sonazoid (GE
      Healthcare, Oslo, Norway) in terms of patient safety and to select the dose to be
      used for lymphatic applications in humans. METHODS: This study was performed in
      12 female volunteers who received bilateral subdermal injections of Sonazoid (1
      or 2 mL dose) in the mid-upper outer quadrant of their breasts at 2 different
      time points. Contrast-enhanced US examinations were performed 0, 0.25, 0.5, 1, 2,
      4, 6, and 24 hours after injection to identify SLNs. RESULTS: Sentinel lymph
      nodes were identified within the first hour after injection as enhanced
      structures, and there was no significant difference by dose in the number of SLNs
      identified (P = .74). The volunteers only had minor adverse experiences (AEs)
      that resolved completely without intervention by study completion. CONCLUSIONS:
      The subdermal use of Sonazoid in this study showed only minor local and
      nonsignificant AEs that were completely resolved without any intervention. Two
      different doses were compared with no significant differences observed between
      them. Hence, the lower dose studied (1 mL) was selected for use in future
      clinical studies.

PMID- 29205454
TI  - Joint mixed-effects models for causal inference with longitudinal data.
AB  - Causal inference with observational longitudinal data and time-varying exposures
      is complicated due to the potential for time-dependent confounding and unmeasured
      confounding. Most causal inference methods that handle time-dependent confounding
      rely on either the assumption of no unmeasured confounders or the availability of
      an unconfounded variable that is associated with the exposure (eg, an
      instrumental variable). Furthermore, when data are incomplete, validity of many
      methods often depends on the assumption of missing at random. We propose an
      approach that combines a parametric joint mixed-effects model for the study
      outcome and the exposure with g-computation to identify and estimate causal
      effects in the presence of time-dependent confounding and unmeasured confounding.
      G-computation can estimate participant-specific or population-average causal
      effects using parameters of the joint model. The joint model is a type of shared
      parameter model where the outcome and exposure-selection models share common
      random effect(s). We also extend the joint model to handle missing data and
      truncation by death when missingness is possibly not at random. We evaluate the
      performance of the proposed method using simulation studies and compare the
      method to both linear mixed- and fixed-effects models combined with g-computation
      as well as to targeted maximum likelihood estimation. We apply the method to an
      epidemiologic study of vitamin D and depressive symptoms in older adults and
      include code using SAS PROC NLMIXED software to enhance the accessibility of the
      method to applied researchers.

PMID- 29205455
TI  - The middle and inner ears of the Palaeogene golden mole Namachloris: A comparison
      with extant species.
AB  - Many living species of golden moles (Chrysochloridae) have greatly enlarged
      middle ear ossicles, believed to be used in the detection of ground vibrations
      through inertial bone conduction. Other unusual features of chrysochlorids
      include internally coupled middle ear cavities and the loss of the tensor tympani
      muscle. Our understanding of the evolutionary history of these characteristics
      has been limited by the paucity of fossil evidence. In this article, we describe
      for the first time the exquisitely preserved middle and inner ears of Namachloris
      arenatans from the Palaeogene of Namibia, visualised using computed tomography,
      as well as ossicles attributed to this species. We compare the auditory region of
      this fossil golden mole, which evidently did not possess a hypertrophied malleus,
      to those of three extant species with similarly sized ear ossicles, Amblysomus
      hottentotus, Calcochloris obtusirostris, and Huetia leucorhinus. The auditory
      region of Namachloris shares many common features with the living species,
      including a pneumatized, trabeculated basicranium and lateral skull wall,
      arteries and nerves of the middle ear contained in bony tubes, a highly coiled
      cochlea, a secondary crus commune, and no identifiable canaliculus cochleae for
      the perilymphatic duct. However, Namachloris differs from extant golden moles in
      the apparent absence of a basicranial intercommunication between the right and
      left ears, the possession of a tensor tympani muscle and aspects of ossicular
      morphology. One Namachloris skull showed what may be pneumatization of some of
      the dorsal cranial bones, extending right around the brain. Although the ossicles
      are small in absolute terms, one of the Huetia leucorhinus specimens had a more
      prominent malleus head than the other. This potentially represents a previously
      unrecognised subspecific difference.

PMID- 29205456
TI  - Automated production of [18 F]FTHA according to GMP.
AB  - 14-(R,S)-[18 F]fluoro-6-thia-heptadecanoic acid is a tracer for fatty acid
      imaging by positron emission tomography. High demand for this tracer required us
      to replace semiautomatic synthesis with a fully automated procedure. An automated
      synthesis device was constructed in-house for multistep nucleophilic 18 F
      fluorination and a control system was developed. The synthesis device was
      combined with a sterile filtration unit and both were qualified. 14-(R,S)-[18
      F]fluoro-6-thia-heptadecanoic acid was produced according to good manufacturing
      practice guidelines set by the European Union. The synthesis includes an initial
      nucleophilic labelling reaction, deprotection, preparative HPLC separation,
      purification of the final product, and formulation for injection. The duration
      and temperature of the reaction and hydrolysis were optimized, and the
      radiochemical stability of the formulated product was determined. The rotary
      evaporator used to evaporate the solvent after HPLC purification was replaced
      with solid phase extraction purification. We also replaced the human serum
      albumin used in the earlier procedure with a phosphate buffer-ascorbic acid
      mixture in the final formulation solution. From 2011 to 2016, we performed 219
      synthesis procedures, 94% of which were successful. The radiochemical yield of 14
      (R,S)-[18 F]fluoro-6-thia-heptadecanoic acid, decay-corrected to the end of
      bombardment, was 13% +/- 6.3%. The total amount of formulated end product was 1.7
      +/- 0.8 GBq at end of synthesis.

PMID- 29205457
TI  - Primary cutaneous secretory carcinoma: A previously overlooked low-grade sweat
      gland carcinoma.
AB  - INTRODUCTION: Twelve cases of primary cutaneous secretory carcinoma (PCSC) have
      been published, 9 showing ETV6-NTRK3 translocation, a characteristic finding
      shared with secretory breast carcinoma and mammary analogue secretory carcinoma.
      CASE REPORT: A 34-year-old female presented a solitary nodule on the right groin.
      Biopsy revealed a secretory carcinoma staining positive with CK7, CAM5.2,
      mammaglobulin and S100 and negative with GATA3, CK20, podoplanin, calponin and
      CDX2. ETV6-NTRK3 was demonstrated by Fluorescence in situ hybridization (FISH).
      DISCUSSION: PCSC is a rare neoplasm, described in the skin in 2009, that affects
      more frequently females with a mean age of 42.3 years and it is most commonly
      located in axilla. Histopathologically, these tumor cells are characterized by
      bubbly eosinophilic secretions diastase-resistant and bland nuclei and they are
      arranged in various growth patterns, including microcystic, tubular, solid and
      papillary. S100, mammoglobin and CK7 are usually positive. We review the main
      histopathological features to rule out histopathologic mimics such as breast
      metastasis, salivary tumors, cribriform carcinoma and primary cutaneous adenoid
      cystic carcinoma. GATA3 negative staining, as in our case, can help to rule out
      breast metastasis. Moreover, long-term benign follow up (144 months) in this case
      as well as follow-up data on outcomes from literature review support that PCSC is
      a low-grade sweat gland carcinoma.

PMID- 29205458
TI  - Multidisciplinary management of refractory insulinomas.
AB  - Insulinomas are predominantly benign (~90%), pancreatic neuroendocrine tumours
      characterized by hyperinsulinaemic hypoglycaemia. They usually present as a small
      (<2 cm), well-demarcated, solitary nodule that can arise in any part of the
      organ. Treatment for sporadic insulinomas is generally aimed at curative surgical
      resection with special consideration in genetic syndromes. Patients with
      significant hypoglycaemia can pose a difficult management challenge. In isolated
      cases where the patient is not medically fit for surgery or with metastatic
      spread, other treatment options are employed. Medical therapy with diazoxide or
      somatostatin analogues is commonly used first line for symptom control, albeit
      with variable efficacy. Other medical options are emerging, including newer
      targeted biological therapies, including everolimus (an mTOR inhibitor),
      sunitinib (a tyrosine kinase inhibitor) and pasireotide, a multisomatostatin
      receptor ligand. Pasireotide and everolimus both cause hyperglycaemia by
      physiological mechanisms synergistic with its antitumour/antiproliferative
      effects. Minimally invasive treatment modalities such as ethanol ablation are
      available in selected cases (particularly in patients unfit for surgery), peptide
      receptor radionuclide therapy (PRRT) can effectively control tumour growth or
      provide symptomatic benefit in metastatic disease, while cytotoxic chemotherapy
      can be used in patients with higher-grade tumours. This review considers the
      developments in the medical and other nonsurgical management options for cases
      refractory to standard medical management. Early referral to a dedicated
      neuroendocrine multidisciplinary team is critical considering the array of
      medical, oncological, interventional radiological and nuclear medical options. We
      discuss the evolving armamentarium for insulinomas when standard medical therapy
      fails.

PMID- 29205459
TI  - Histomorphological features of the tongue of the Eurasian teal (Anas crecca).
AB  - This study presents the histomorphological features of tongue in Eurasian teal
      (Anas crecca); the smallest extant dabbling duck. Heads of four adult males and
      four adult females were used in this study. The results illustrate a tongue with
      three different parts; the apex with a lingual nail in ventral surface, the body
      with a lingual prominence in caudal part and some large and small conical
      papillae in lateral sides and the root, that was covered with many conical
      papillae in different sizes. Histological results revealed two types of
      keratinized and non-keratinized epithelium covering parts of the tongue. The
      lingual salivary glands were observed in the lamina propria of the body and root
      of the tongue showed strongly periodic acid-Schiff (PAS)-positive reaction. The
      yellow adipose tissue was located under the lamina propria on the body and root
      of the tongue. The filiform papillae between the conical papillae of the body
      were arranged densely. The sensory organs, which contain sensory receptors
      (Grandry and Herbst corpuscles), were located in the lamina propria of the body
      of the tongue. In conclusion, the anatomical and histological structure of the
      Eurasian teal' tongue was generally similar to its family members such as
      domestic goose and duck but showed some differences that may be adoptions to the
      bird's habitat and mode of feeding.

PMID- 29205460
TI  - Successful treatment with i.v. immunoglobulin for localized cutaneous
      immunoglobulin light chain kappa-positive amyloidosis associated with
      dermatomyositis.

PMID- 29205461
TI  - Case of papuloerythroderma of Ofuji-like eruption during the course of bullous
      pemphigoid.

PMID- 29205462
TI  - Comprehensive management reduces incidence and mortality of acute chest syndrome
      in patients with sickle cell disease.

PMID- 29205463
TI  - Mode of birth and postnatal health-related quality of life after one previous
      cesarean in three European countries.
AB  - BACKGROUND: How a woman gives birth can affect her health-related quality of life
      (HRQoL). This study explored HRQoL at 3 months postpartum in women with a history
      of one previous cesarean in three European countries. METHODS: A prospective
      longitudinal survey, embedded within a cluster randomized trial in three
      countries, exploring women's postnatal HRQoL up to 3 months postpartum. The Short
      Form Six-Dimensions (SF-6D) was used to measure HRQoL, and multivariate analyses
      were used to examine the relationship with mode of birth. RESULTS: Complete data
      were available from 880 women. Women with a spontaneous vaginal birth had the
      highest HRQoL scores, whereas women with an emergency repeat cesarean (P = .01)
      had the lowest. Postnatal readmission of the mother (P = .03), having public
      health insurance (P = .04), and a low antenatal HRQoL score (P < .01) contributes
      to poorer HRQoL scores. More specifically, women with a spontaneous vaginal birth
      had significantly higher HRQoL scores on the vitality dimension compared with
      women with an emergency repeat cesarean (P = .04). CONCLUSIONS: In women with low
      risk factors, repeat cesareans result in a poorer HRQoL compared with vaginal
      birth. When there are no contraindications for vaginal birth, women with a
      history of one previous cesarean should be encouraged to give birth vaginally
      rather than have an elective repeat cesarean.

PMID- 29205464
TI  - Interleukin-17 family cytokines in protective immunity against infections: role
      of hematopoietic cell-derived and non-hematopoietic cell-derived interleukin-17s.
AB  - Interleukin-17 family cytokines, consisting of six members, participate in immune
      response in infections and autoimmune and inflammatory diseases. The prototype
      cytokine of the family, IL-17A, was originally identified from CD4+ T cells which
      are now termed Th17 cells. Later, IL-17A-producing cells were expanded to include
      various hematopoietic cells, namely CD8+ T cells (Tc17), invariant NKT cells,
      gammadelta T cells, non-T non-B lymphocytes (termed type 3 innate lymphoid cells)
      and neutrophils. Some IL-17 family cytokines other than IL-17A are also expressed
      by CD4+ T cells: IL-17E by Th2 cells and IL-17F by Th17 cells. IL-17A and IL-17F
      induce expression of pro-inflammatory cytokines to induce inflammation and anti
      microbial peptides to kill pathogens, whereas IL-17E induces allergic
      inflammation. However, the functions of other IL-17 family cytokines have been
      unclear. Recent studies have shown that IL-17B and IL-17C are expressed by
      epithelial rather than hematopoietic cells. Interestingly, expression of IL-17E
      and IL-17F by epithelial cells has also been reported and epithelial cell-derived
      IL-17 family cytokines shown to play important roles in immune responses to
      infections at epithelial sites. In this review, we summarize current information
      on hematopoietic cell-derived IL-17A and non-hematopoietic cell-derived IL-17B,
      IL-17C, IL-17D, IL-17E and IL-17F in infections and propose functional
      differences between these two categories of IL-17 family cytokines.

PMID- 29205465
TI  - Gross anatomy of the heart of the alpaca (Vicugna pacos, Linnaeus 1758).
AB  - The available information about anatomical characteristics of the cardiovascular
      system of the alpaca (Vicugna pacos, Linnaeus 1758) is scarce. The general
      objective of this work was to describe its heart anatomy. We dissected six adult
      animals and five neonates. The heart of the alpaca was located in the middle
      mediastinum, with a craniocaudal extension from the third to the sixth rib. No
      ligament that connected the fibrous pericardium to the sternum or to the
      diaphragm was detected. In the right atrium, there was a developed crista
      terminalis and small pectinate muscles. In the right ventricle, the septomarginal
      trabecula was very large. From the proximities of the interventricular septum
      arose small septomarginal trabeculae that ended in carnous trabeculae of the
      septal wall. The left atrium included little developed pectinate muscles. On the
      left ventricle, both papillary muscles were bilobed. Two left septomarginal
      trabeculas were detected in this ventricle. The left subclavian artery was
      originated from the aortic arch separately from the brachiocephalic trunk, and
      bicarotid trunk was present. The other branches of the subclavian artery were
      similar to the domestic ruminants. The arterial supply of the heart was of the
      right type. In conclusion, the heart anatomy of alpaca and the irrigation of
      thoracic cavity were more similar to those of old world camels and different from
      domestic ruminants.

PMID- 29205466
TI  - Ischemic core thresholds change with time to reperfusion: A case control study.
AB  - INTRODUCTION: We aimed to identify whether acute ischemic stroke patients with
      known complete reperfusion after thrombectomy had the same baseline computed
      tomography perfusion (CTP) ischemic core threshold to predict infarction as
      thrombolysis patients with complete reperfusion. METHODS: Patients who underwent
      thrombectomy were matched by age, clinical severity, occlusion location, and
      baseline perfusion lesion volume to patients who were treated with intravenous
      alteplase alone from the International Stroke Perfusion Imaging Registry. A pixel
      based analysis of coregistered pretreatment CTP and 24-hour diffusion-weighted
      imaging (DWI) was then undertaken to define the optimum CTP thresholds for the
      ischemic core. RESULTS: There were 132 eligible thrombectomy patients and 132
      matched controls treated with alteplase alone. Baseline National Institutes of
      Health Stroke Scale (median, 15; interquartile range [IQR], 11-19), age (median,
      65; IQR, 59-80), and time to intravenous treatment (median, 153 minutes; IQR, 82
      315) were well matched (all p > 0.05). Despite similar baseline CTP ischemic core
      volumes using the previously validated measure (relative cerebral blood flow
      [rCBF], <30%), thrombectomy patients had a smaller median 24-hour infarct core of
      17.3ml (IQR, 11.3-32.8) versus 24.3ml (IQR, 16.7-42.2; p = 0.011) in alteplase
      treated controls. As a result, the optimal threshold to define the ischemic core
      in thrombectomy patients was rCBF <20% (area under the curve [AUC], 0.89; 95% CI,
      0.84, 0.94), whereas in alteplase controls the optimal ischemic core threshold
      remained rCBF <30% (AUC, 0.83; 95% CI, 0.77, 0.85). INTERPRETATION: Thrombectomy
      salvaged tissue with lower CBF, likely attributed to earlier reperfusion. For
      patients who achieve rapid reperfusion, a stricter rCBF threshold to estimate the
      ischemic core should be considered. Ann Neurol 2017;82:995-1003.

PMID- 29205467
TI  - Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole
      derivatives as VEGFR-2 inhibitors.
AB  - As the blockade of the VEGFR-2 signaling pathway is a viable approach in cancer
      therapy, the present study focuses on a series of pyrazole based VEGFR-2
      inhibitors that were designed on the basis of the hybridization approach,
      supported by docking and in silico computational studies. The designed compounds
      were synthesized through facile synthetic methods and the structures were
      confirmed by 1 H NMR, 13 C NMR, MS and elemental analysis. The compounds were
      screened for in vitro antiproliferative activity against the HT-29 (human colon
      cancer) and MCF-7 (human breast cancer) cell lines by MTT assay. The compounds
      were also studied for in vitro inhibitory activity against VEGFR-2 kinase. Among
      all the tested compounds, compound 6h emerged as a potent agent in the
      antiproliferative study against HT-29 and MCF-7 cells, with IC50 values of 2.36
      and 6.59 MUM, respectively. Moreover, the same compound exhibited the highest
      VEGFR-2 inhibitory activity with an IC50 value of 1.89 MUM. In docking studies,
      the designed compounds showed similar and essential key interactions as those of
      known VEGFR-2 inhibitors. The present study may lead to new molecules in the
      development of anticancer agents targeting VEGFR-2.

PMID- 29205469
TI  - Expertise in physiological breech birth: A mixed-methods study.
AB  - BACKGROUND: The safety of vaginal breech birth depends on the expertise of birth
      attendants, yet the meaning of "expertise" remains unclear and subjectively
      defined. The objective of this study was to define expertise and the roles
      experts may play in expanding access to this service. METHODS: We performed an
      integrative analysis of two strands of data concerning expertise in physiological
      breech birth, including the following: survey data from a Delphi study involving
      26 very experienced clinicians (mean experience = 135 breech births) and 2
      service user representatives, and interviews from a grounded theory study of 14
      clinicians more moderately experienced with physiological methods (5-30 upright
      breech births). Data were pooled and analyzed using constant comparative methods.
      RESULTS: Expertise is defined by its ongoing function, the generation of
      comparatively good outcomes, and confidence and competence among colleagues.
      Although clinical experience is important, expertise is developed and expressed
      in social clinical roles, which expand as experience grows: clinician, mentor,
      specialist, and expert. To develop expertise within a service, clinicians who
      have an interest in breech birth should be supported to perform these roles
      within specialist teams. CONCLUSIONS: Specialist breech teams may facilitate the
      development of expertise within maternity care settings. Evaluation of expertise
      based on enablement of women and colleagues, as well as outcomes, will
      potentially avoid the pitfalls of alienation produced by some forms of specialist
      authority.

PMID- 29205468
TI  - Case of epidermolysis bullosa acquisita with concomitant anti-laminin-332
      antibodies.
AB  - Subepidermal autoimmune blistering disease including bullous pemphigoid,
      pemphigoid gestationis, mucous membrane pemphigoid, anti-laminin-gamma1
      pemphigoid, linear immunoglobulin A bullous disease and epidermolysis bullosa
      acquisita (EBA), are all characterized by direct immunofluorescence microscopy or
      immunoglobulin deposition on the basement membrane zone. Among them, EBA is a
      rare acquired subepidermal autoimmune blistering disease of the skin and mucous
      membranes reactive with type VII collagen, a major component of the epidermal
      basement membrane zone. Anti-laminin-332-type mucous membrane pemphigoid has
      pathogenic autoantibodies against laminin-332, which is a basement membrane
      heterotrimeric protein composed of alpha3, beta3 and gamma2 laminin chains. We
      describe a 73-year-old Japanese man presenting with multiple, annular, tense
      blisters on the lower legs and oral lesions. Despite the severe clinical
      manifestations, the disease was successfully controlled by combination therapy of
      oral prednisolone and mizoribine. This case was confirmed to have autoantibodies
      to both type VII collagen and laminin-332 alpha3 chain by indirect
      immunofluorescence of 1 mol NaCl-split normal human skin, various immunoblot
      analyses and enzyme-linked immunosorbent assays. This case was a rare case of EBA
      with concomitant anti-laminin-332 antibodies.

PMID- 29205470
TI  - New onset of psoriasis during nivolumab treatment for lung cancer.

PMID- 29205471
TI  - Gender and mental health: An examination of procedural justice in a specialized
      court context.
AB  - The procedural justice framework has been applied in the criminal justice
      contexts of policing, corrections, and courts. According to this perspective,
      fair treatment, respectful dialogue and being given a proper voice will
      contribute to citizens' positive views of authority figures. While this
      literature has grown immensely, several questions remain unanswered. Do males and
      females perceive similar levels of procedural justice? Does mental health status
      influence perceptions of fair treatment? Whether procedural justice is a general
      perspective that can be applied across social groupings has important
      implications for correctional treatment in that programs that truly "work" for
      all are more cost-effective. Toward that end, the current study investigates the
      relationships among procedural justice perceptions, gender, and mental health
      status in specialized drug courts, a context that has received little empirical
      attention. We do so using secondary data originally collected between 2003 and
      2009 for Rossman, Roman, Zweig, Rempel and Lindquist's Multisite Adult Drug Court
      Evaluation (MADCE). Results from a full-sample analysis reveal that women report
      higher levels of procedural justice; that drug court participation significantly
      influences procedural justice perceptions; and that depressive symptomology is a
      significant predictor of procedural justice perceptions. In male- and female
      specific subsamples, drug court participation exerts similar effects for males
      and females, as does depressive symptomology. Implications for theory, research,
      and practice are discussed.

PMID- 29205473
TI  - In situ evaluation of surface roughness and micromorphology of temporary soft
      denture liner materials at different time intervals.
AB  - OBJECTIVE: To perform an in situ evaluation of surface roughness and
      micromorphology of two soft liner materials for dentures at different time
      intervals. BACKGROUND: The surface roughness of materials may influence the
      adhesion of micro-organisms and inflammation of the mucosal tissues. The in situ
      evaluation of surface roughness and the micromorphology of soft liner materials
      over the course of time may present results different from those of in vitro
      studies, considering the constant presence of saliva and food, the changes in
      temperature and the pH level in the oral cavity. MATERIALS AND METHODS: Forty
      eight rectangular specimens of each of the two soft liner materials were
      fabricated: a silicone-based material (Mucopren Soft) and an acrylic resin-based
      material (Trusoft). The specimens were placed in the dentures of 12 participants
      (n = 12), and the materials were evaluated for surface roughness and
      micromorphology at different time intervals: 0, 7, 30 and 60 days. Roughness (Ra)
      was evaluated by means of a roughness tester. Surface micromorphology was
      evaluated by scanning electron microscopy. RESULTS: Analysis of variance for
      randomised block design and Tukey's test showed that surface roughness values
      were lower in the groups using the silicone-based material at all the time
      intervals (P < .0001). The average surface roughness was higher at time interval
      0 than at the other intervals, for both materials (P < .0001). The surface
      micromorphology showed that the silicone material presented a more regular and
      smoother surface than the acrylic resin-based material. CONCLUSION: The surface
      roughness of acrylic resin-based and silicone-based denture soft liner materials
      decreased after 7 days of evaluation, leading to a smoother surface over time.
      The silicone-based material showed lower roughness values and a smoother surface
      than the acrylic resin-based material, thereby making it preferred when selecting
      more appropriate material, due its tendency to promote less biofilm build-up.

PMID- 29205474
TI  - Successful treatment of facial milia in an infant with orofaciodigital syndrome
      type 1.
AB  - We report the successful treatment of multiple facial milia with manual
      extraction and tretinoin in a child with orofaciodigital syndrome type 1.
      Treatment with topical medications may be insufficient in individuals with
      orofaciodigital syndrome type 1, and pitted scarring is often a sequala. This
      case demonstrates that manual extraction is well tolerated and effective in the
      treatment of multiple milia. In addition, clinicians need to be aware of this
      rare genetic condition, which commonly presents de novo and can lead to
      significant morbidity if untreated.

PMID- 29205475
TI  - Single-unit activities during the transition to seizures in deep mesial
      structures.
AB  - Focal seizures are assumed to arise from a hypersynchronous activity affecting a
      circumscribed brain region. Using microelectrodes in seizure-generating deep
      mesial regions of 9 patients, we investigated the firing of hundreds of single
      neurons before, during, and after ictal electroencephalogram (EEG) discharges.
      Neuronal spiking activity at seizure initiation was highly heterogeneous and not
      hypersynchronous. Furthermore, groups of neurons showed significant changes in
      activity minutes before the seizure with no concomitant changes in the
      corresponding macroscopic EEG recordings. Altogether, our findings suggest that
      only limited subsets of neurons in epileptic depth regions initiate the seizure
      onset and that ictogenic mechanisms operate in submillimeter-scale microdomains.
      Ann Neurol 2017 Ann Neurol 2017;82:1022-1028.

PMID- 29205476
TI  - Subcutaneous granuloma annulare involving the scalp.
AB  - Subcutaneous granuloma annulare (SGA) is an uncommon subtype of granuloma
      annulare. There are few reports of this entity solely affecting the scalp. We
      report a case of biopsy-proven SGA in a 21-month-old boy with six asymptomatic,
      rock-hard scalp nodules.

PMID- 29205472
TI  - Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.
AB  - OBJECTIVE: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy,
      encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic
      variants in SERAC1. METHODS: This multicenter study addressed the course of
      disease for each organ system. Metabolic, neuroradiological, and genetic findings
      are reported. RESULTS: Sixty-seven individuals (39 previously unreported) from 59
      families were included (age range = 5 days-33.4 years, median age = 9 years). A
      total of 41 different SERAC1 variants were identified, including 20 that have not
      been reported before. With the exception of 2 families with a milder phenotype,
      all affected individuals showed a strikingly homogeneous phenotype and time
      course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen
      in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia
      (91%) was seen, followed by progressive spasticity (82%, median onset = 15
      months) and dystonia (82%, 18 months). The majority of affected individuals never
      learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never
      learned to speak, and nearly all had significant intellectual disability (88%).
      Magnetic resonance imaging features were accordingly homogenous, with bilateral
      basal ganglia involvement (98%); the characteristic "putaminal eye" was seen in
      53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all
      patients (98%). Supportive treatment focused on spasticity and drooling, and was
      effective in the individuals treated; hearing aids or cochlear implants did not
      improve communication skills. INTERPRETATION: MEGDHEL syndrome is a progressive
      deafness-dystonia syndrome with frequent and reversible neonatal liver
      involvement and a strikingly homogenous course of disease. Ann Neurol
      2017;82:1004-1015.

PMID- 29205477
TI  - Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate
      gadoteridol enhancement in high grade gliomas.
AB  - PURPOSE: Delayed ferumoxytol enhancement on T1 -weighted images appears visually
      similar to gadoteridol enhancement. The purpose of this study was to
      quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with
      an objective, semi-automated method. METHODS: 206 sets of post-gadoteridol and 24
      h post-ferumoxytol T1 -weighted scans from 58 high grade glioma patients were
      analyzed (9 pre-chemoradiation, 111 < 90 days post-chemoradiation, 21 > 90 days
      post-chemoradiation, 65 post-bevacizumab scans). Enhancement volumes and signal
      intensities normalized to normal appearing tissue proximal to enhancement were
      calculated with a semi-automated method. Enhancement cube root volumes (D) and
      signal intensities (SI) were compared between the 2 contrast agents, and relative
      difference of D and SI were compared in different treatment groups with
      multivariate analysis. Within patient differences in D and SI before and after
      treatment with bevacizumab or steroid were assessed in 26 patients in each
      treatment group. RESULTS: When compared to gadoteridol, ferumoxytol D was 13.83%
      smaller and SI was 7.24% lower (P < 0.0001). The relative differences in D and SI
      between the 2 contrast agents were not significantly different between treatment
      groups (P > 0.05). Relative difference in D and SI did not change significantly
      in response to bevacizumab (P = 0.5234 and P = 0.2442, respectively) or to
      steroid (P = 0.3774, P = 0.0741) in the within patient comparison. CONCLUSION:
      The correlation between the 2 contrast agents' enhancement size and signal
      intensity and their similar behavior in response to therapy suggest that
      ferumoxytol can be used for revealing enhancement in high grade glioma patients.
      Magn Reson Med 80:224-230, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 29205478
TI  - Preclinical models for orthopedic research and bone tissue engineering.
AB  - In this review, we broadly define and discuss the preclinical rodent models that
      are used for orthopedics and bone tissue engineering. These range from
      implantation models typically used for biocompatibility testing and high
      throughput drug screening, through to fracture and critical defect models used to
      model bone healing and severe orthopedic injuries. As well as highlighting the
      key methods papers describing these techniques, we provide additional commentary
      based on our substantive practical experience with animal surgery and in vivo
      experimental design. This review also briefly touches upon the descriptive and
      functional outcome measures and power calculations that are necessary for an
      informative study. Obtaining informative and relevant research outcomes can be
      very dependent on the model used, and we hope this evaluation of common models
      will serve as a primer for new researchers looking to undertake preclinical bone
      studies. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res 36:832-840, 2018.

PMID- 29205479
TI  - Excellent response to ustekinumab in a 9-year-old girl with severe psoriasis.
AB  - We report the case of a 9-year-old girl with severe plaque psoriasis refractory
      to multiple topical and systemic therapies. Physical examination revealed
      extensive, erythematous plaques with overlying thick scales that covered more
      than 80% of her body surface area, which included the face, scalp, trunk, and
      limbs. Because of the severity of the disease and lack of treatment response to
      other systemic therapies, she was treated with ustekinumab. Three weeks after
      ustekinumab was initiated, her psoriatic lesions fully cleared.

PMID- 29205480
TI  - A z-gradient array for simultaneous multi-slice excitation with a single-band RF
      pulse.
AB  - PURPOSE: Multi-slice radiofrequency (RF) pulses have higher specific absorption
      rates, more peak RF power, and longer pulse durations than single-slice RF
      pulses. Gradient field design techniques using a z-gradient array are
      investigated for exciting multiple slices with a single-band RF pulse. THEORY AND
      METHODS: Two different field design methods are formulated to solve for the
      required current values of the gradient array elements for the given slice
      locations. The method requirements are specified, optimization problems are
      formulated for the minimum current norm and an analytical solution is provided. A
      9-channel z-gradient coil array driven by independent, custom-designed gradient
      amplifiers is used to validate the theory. RESULTS: Performance measures such as
      normalized slice thickness error, gradient strength per unit norm current, power
      dissipation, and maximum amplitude of the magnetic field are provided for various
      slice locations and numbers of slices. Two and 3 slices are excited by a single
      band RF pulse in simulations and phantom experiments. CONCLUSION: The possibility
      of multi-slice excitation with a single-band RF pulse using a z-gradient array is
      validated in simulations and phantom experiments. Magn Reson Med 80:400-412,
      2018. (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 29205482
TI  - Low-frequency ESR studies on permeable and impermeable deuterated nitroxyl
      radicals in corn oil solution.
AB  - Low-frequency electron spin resonance studies were performed for 2 mM
      concentration of deuterated permeable and impermeable nitroxyl spin probes, 3
      methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl and 3-carboxy-2,2,5,5,
      tetramethyl-1-pyrrolidinyloxy in pure water and various concentrations of corn
      oil solution. The electron spin resonance parameters such as the line width,
      hyperfine coupling constant, g factor, rotational correlation time, permeability,
      and partition parameter were estimated. The broadening of line width was observed
      for nitroxyl radicals in corn oil mixture. The rotational correlation time
      increases with increasing concentration of corn oil, which indicates the less
      mobile nature of spin probe in corn oil mixture. The membrane permeability and
      partition parameter values were estimated as a function of corn oil
      concentration, which reveals that the nitroxyl radicals permeate equally into the
      aqueous phase and oil phase at the corn oil concentration of 50%. The electron
      spin resonance spectra demonstrate the permeable and impermeable nature of
      nitroxyl spin probes. From these results, the corn oil concentration was
      optimized as 50% for phantom studies. In this work, the corn oil and pure water
      mixture phantom models with various viscosities correspond to plasma membrane,
      and whole blood membrane with different hematocrit levels was studied for
      monitoring the biological characteristics and their interactions with permeable
      nitroxyl spin probe. These results will be useful for the development of electron
      spin resonance and Overhauser-enhanced magnetic resonance imaging modalities in
      biomedical applications.

PMID- 29205483
TI  - Mechanical properties of Triclosan sutures.
AB  - To avoid infections and wound healing disorders, Triclosan coated sutures have
      been invented. Little is known of these sutures regarding their tensile
      properties. Three different Triclosan coated sutures (Vicryl 1 plus, PDS 0 plus,
      Monocryl 3-0 plus) were tested at several time points over 42 days regarding load
      to failure, strain, and stiffness compared to their non-coated versions (Vicryl
      1, PDS 0, Monocryl 3-0). Four different measurement points were made. Suture
      loops were fixed in a material testing machine over two metal bars which were
      moved apart creating a stress to the fiber. Unpaired, two-tailed t-test were
      performed for each group (untreated and treated) while level of significance was
      defined at a level of p < 0.05. Vicryl 1 was significantly stronger on day 14
      than Vicryl 1 plus (p = 0.033). On day 28, significant changes were found in PDS
      0 which was weaker compared to PDS 0 plus (p = 0.039) and Vicryl 1 which was
      stronger than Vicryl 1 plus (p = 0.032). We have seen that Vicryl 1 plus sutures
      are significantly weaker according to loading to failure after 14 and 28 days,
      which might cause incisional hernias. PDS 0 sutures are used to reconstruct
      tendons, therefore a longer durableness might be of interest as re-ruptures of
      tendons are problematic. Our in vitro findings support, the use of Triclosan
      coated PDS plus sutures and Vicryl sutures as they show a longer resistance. (c)
      2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:1777-1782, 2018.

PMID- 29205484
TI  - Subclinical left ventricular systolic and diastolic dysfunction in type 1
      diabetic children and adolescents with good metabolic control.
AB  - OBJECTIVE: Cardiac dysfunction is a well-known consequence of diabetes mellitus.
      This study was designed to assess whether type 1 diabetic children and
      adolescents with good metabolic control have early echocardiographic signs of
      subclinical left ventricular dysfunction and whether diabetes duration has any
      influence, using conventional and nonconventional echocardiographic tools.
      METHODS: A total of 100 patients with type 1 diabetes mellitus and 80 gender- and
      age-matched healthy controls were included. The cases underwent standard
      conventional transthoracic echocardiography, tissue Doppler imaging, and two
      dimensional speckle tracking echocardiography. None of the diabetic patients had
      signs of renal, retinal, or neurological complications of the disease, and all
      were good metabolic control (mean HbA1c <7.5%). RESULTS: There was no difference
      among groups in relation to age, sex, body mass index, and blood pressure.
      Conventional echocardiographic parameters were similar between diabetic and
      nondiabetic subjects except increased mitral valve peak A-wave and significantly
      lower mitral E/A ratio in diabetics. Diabetic patients had more advanced
      diastolic dysfunction with TDI analysis. In the diabetic group, left ventricular
      global longitudinal, circumferential, and radial strain and strain rate were
      significantly lower compared with the controls. There was a positive correlation
      between diabetes duration and cardiac dysfunction. CONCLUSION: The results of
      this study showed that the diabetic children and adolescents with good metabolic
      control had diastolic dysfunction when assessed with either conventional or
      tissue Doppler echocardiography. Also diabetic patients had subclinical LV
      systolic dysfunction with a normal LVEF which can be detected with 2D speckle
      tracking echocardiography.

PMID- 29205485
TI  - Combination of increased visceral fat and long segment involvement: Development
      and validation of an updated imaging marker for differentiating Crohn's disease
      from intestinal tuberculosis.
AB  - BACKGROUND AND AIM: Computed tomographic (CT) features (long segment, ileocaecal
      area involvement, and lymph nodes > 1 cm) have demonstrated good specificity but
      poor sensitivity, while visceral to subcutaneous fat ratio on CT (VF/SC > 0.63)
      has moderate sensitivity and specificity in differentiating Crohn's disease (CD)
      and intestinal tuberculosis (ITB). This study aims to develop and validate an
      updated model incorporating CT features and VF/SC to improve the diagnostic
      accuracy of imaging in differentiating CD/ITB. METHODS: Computed tomographic
      features and VF/SC were documented in two cohorts (development [n = 59, follow
      up: January 2012 to November 2014] and validation [n = 69, follow-up: December
      2014 to December 2015]) of CD/ITB patients diagnosed by standard criteria.
      Patients with normal CT were excluded. Features significantly different between
      CD/ITB were incorporated into a model. RESULTS: In both the cohorts, necrotic
      lymph nodes were exclusive for ITB (23.1% vs 0% and 43.3% vs 0%), while long
      segment involvement (57.6% vs 7.7%, P < 0.001, and 52.6% vs 16.1%, P < 0.001) and
      VF/SC ratio > 0.63 (72.7% vs 19.2%, P < 0.001, and 81.6% vs 25.8%, P < 0.001)
      were significantly more common in CD. A risk score of 2, based upon long segment
      involvement and VF/SC ratio > 0.63, had an excellent specificity of 100% and 100%
      and sensitivity of 54% and 50% for CD in development and validation cohorts,
      respectively. Based upon these features, in 43% patients with the diagnostic
      dilemma of CD/ITB, a definite diagnosis based only on imaging could be made.
      CONCLUSION: Necrotic lymph nodes are exclusive for ITB, and the combination of
      long segment involvement and VF/SC ratio > 0.63 is exclusive for CD, and these
      features can make a definite diagnosis in 43% patients with a CD/ITB dilemma.

PMID- 29205486
TI  - Induction of axon growth in the adult brain: A new approach to restoration in
      Parkinson's disease.

PMID- 29205488
TI  - Single stage functional reconstruction of both peroneal tendons and overlying
      skin with an anterolateral thigh flap and vascularized fascia lata: A case
      report.
AB  - Reconstruction of complex soft tissue defects in the distal lower leg remains
      challenging, since anatomical constraints limit the local options available in
      this area. In this report, we present a case of single stage functional
      reconstruction of both peroneal tendons and overlying skin with an anterolateral
      thigh flap and vascularized fascia lata. A 55-year-old patient underwent wide
      excision of a synovial sarcoma in the distal lower leg, which resulted in a
      complex defect including the peroneus longus and brevis tendons (10 cm), and the
      overlying skin (14 * 8 cm). Functional reconstruction was achieved in a single
      stage with a composite anterolateral thigh flap with vascularized fascia lata of
      similar dimensions to those of the defect. The fascia lata component of the flap
      was longitudinally split in two segments. Each of them was rolled up, and that
      way, two separate vascularized neotendons were created. The neotendons bridged
      the gap of peroneal tendons, whereas the skin paddle of the flap provided stable
      soft tissue coverage to the reconstructed tendons. Flap pedicle was anastomosed
      to the anterior tibial vessels. Early and late postoperative periods were
      uneventful. Follow up at 1 year postoperatively showed excellent neotendon
      incorporation, as well as a very good functional and aesthetic outcome. The use
      of the method described may be a useful alternative in single stage functional
      reconstruction of composite defects comprising two or even more tendons and the
      overlying skin.

PMID- 29205487
TI  - The impact of unfractionated heparin or bivalirudin on patients with stable
      coronary artery disease undergoing percutaneous coronary intervention.
AB  - OBJECTIVES: To compare bleeding and clinical events of patients with stable
      angina or silent ischemia undergoing percutaneous coronary intervention (PCI)
      treated with unfractionated heparin (UFH) or bivalirudin. BACKGROUND: Few direct
      comparisons between UFH monotherapy versus bivalirudin exist for patients with
      stable ischemic heart disease undergoing PCI. METHODS: A prospective,
      investigator-initiated, single-center, single-blinded, randomized trial of UFH
      versus bivalirudin was conducted. The primary endpoint was all bleeding (major
      and minor) from index-hospitalization to 30 days post discharge. Secondary
      endpoints included major adverse cerebral and cardiovascular events (MACCE) and
      net adverse clinical events (NACE). RESULTS: Two-hundred-sixty patients were
      randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137)
      (53%) There were no significant differences in baseline clinical and angiographic
      characteristics between the two groups. Primary endpoint was similar in both
      groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates
      were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs
      0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to
      UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI:
      1.00-13.3.6). Death and stent thrombosis rates were low and similar in both
      groups. Radial access was associated with fewer bleeding events compared to
      femoral access but not statistically significant (P = 0.29). CONCLUSIONS: Among
      patients with stable angina or silent ischemia, there was no difference between
      UFH and bivalirudin in bleeding rates up to 30-days post-PCI. MACCE and NACE were
      higher among the bivalirudin group. Radial access was associated with a
      numerically lower rate of bleeding compared with femoral access.

PMID- 29205489
TI  - Beyond the lysosome: Cholesterol role on endoplasmic reticulum and lipid droplets
      in Parkinson's disease.

PMID- 29205490
TI  - National conservation science conferences as a means of bridging conservation
      science and practice.

PMID- 29205491
TI  - Prognostic Value of Cardiac Troponin I and L-Lactate in Blood of Dairy Cows
      Affected by Downer Cow Syndrome.
AB  - BACKGROUND: The downer cow syndrome (DCS) is a challenging health issue in the
      dairy industry. No cow-side test is available to provide an accurate prognosis
      for DCS cases in farm settings. HYPOTHESIS/OBJECTIVES: Local or systemic
      hypoperfusion and myocardial lesions lead to an increase in blood concentration
      of biomarkers cardiac troponin I (cTnI) and L-lactate. The objective was to
      determine the prognostic values of these biomarkers assessed cow-sides in
      addition to clinical examinations in prognostication of a negative outcome (NO:
      death or euthanasia within 7 days). ANIMALS: 218 client-owned dairy cows affected
      by DCS. METHODS: In a prospective study, animals were monitored for 60 days after
      inclusion of each cow. Blood cTnI and L-lactate concentrations were measured on
      the day of inclusion. The prognostic accuracy of both biomarkers and physical
      examination variables was estimated to predict NO. A mixed multivariable logistic
      regression model was used for data analysis. RESULTS: Prevalence of NO in this
      study was 63% on day 7. Troponin concentrations greater than 0.7 ng/mL had
      sensitivity and specificity of 54.1% (95% CI: 45.3-62.7%) and 78.4% (95% CI: 67.3
      87.1%), respectively, for predicting NO. Blood L-lactate was not associated with
      the outcome. The multivariable model revealed that heart rate >100 bpm (OR; 95%
      CI: 3.7; 1.3-10.2) and cTnI > 0.7 ng/mL (OR; 95% CI: 5.5; 2.1-14.6) were
      associated with the risk of NO. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Hypertroponinemia and tachycardia were associated with reduced survival in DCS
      cases. The use of cow-side blood cTnI concentrations and heart rate could help to
      rapidly identify cows in farm setting that have poor chances of recovery and
      would benefit from a more aggressive treatment or euthanasia.

PMID- 29205492
TI  - 9-month results of polymer-free sirolimus eluting stents in young patients
      compared to a septuagenarian and octogenarian all-comer population.
AB  - OBJECTIVES: To evaluate the 9-month safety and efficacy of polymer-free sirolimus
      eluting drug eluting stents in septuagenarians and octogenarians. METHODS: An all
      comer, worldwide single armed trial (ClinicalTrials.gov Identifier NCT02629575)
      was conducted to demonstrate the safety and efficacy of an ultra-thin strut,
      polymer-free sirolimus eluting stent (PF-SES). The primary endpoint was the 9
      month target revascularization rate (TLR). Secondary endpoints included the rates
      of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC)
      in septuagenarians (>=70 years, <80 years), and in octogenarians (>=80 years) to
      be compared to the younger patient group (<70 years). RESULTS: A total of 1607
      patients were treated with PF-SES in the sub-70-year-old age group, 694 in
      septuagenarians, and 371 in the octogenarian patient group. At 9 months, the MACE
      rates were 7.2% in octogenarians, 5.3% in septuagenarians, and 3.0% in the
      younger patient group (P = 0.001). These were mostly driven by all-cause
      mortality (4.4% vs 1.9% vs 0.6%, P < 0.001) while the TLR rates were only
      numerically lower in the younger age group (P = 0.080). BARC 1-5 bleeding events
      were more frequent in the older age group (1.9% vs 2.7% vs 4.6%, P = 0.012)
      whereas the rates for ST were not different (0.7% vs 0.6% vs 0.6%, P = 0.970).
      CONCLUSIONS: In octogenarians treated with PF-SES, the rates for MACE, overall
      mortality, and bleeding are higher as compared to the younger age groups.
      However, the rates for TLR and ST were not significantly different across the
      investigated age groups. PF-SES are safe and effective in octogenarians.

PMID- 29205494
TI  - Acral-accentuated exanthem in an infant with parechovirus meningitis.
AB  - We report a case of an infant who had presented with fever and an acral
      accentuated rash, for which his cerebrospinal fluid returned positive for
      parechovirus. He was treated symptomatically and discharged well, with no long
      term complications.

PMID- 29205493
TI  - Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and
      Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy.
AB  - BACKGROUND: Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary
      and vary across institutions and clinicians. Similarly, subjective guidelines are
      utilized for the administration of prophylactic antibiotics in neutropenic dogs.
      OBJECTIVES: To evaluate the impact of various ANC cutoffs on chemotherapy
      administration in dogs with lymphoma treated with CHOP chemotherapy and to
      determine whether an association between prechemotherapy ANC and subsequent
      toxicity exists. The secondary objective was to evaluate a currently used ANC
      cutoff to indicate prescription of prophylactic antibiotics. ANIMALS: Dogs
      diagnosed with lymphoma treated with CHOP chemotherapy (n = 64). METHODS: Six
      hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 *
      103 /MUL, 2.0 * 103 /MUL, and 2.5 * 103 /MUL were assessed. The presence of an
      association between prechemotherapy ANC class and toxicity was determined.
      Afebrile neutropenic dogs with ANC <1.5 * 103 /MUL but above the criteria for
      prophylactic antibiotics were evaluated. RESULTS: Chemotherapy was not
      administered in 7% of visits with an ANC cutoff of 1.5 * 103 /MUL; chemotherapy
      would not have been administered in 10% and 16% of visits with an ANC cutoff of
      2.0 * 103 /MUL or 2.5 * 103 /MUL, respectively. There was no association among
      the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75-1.5
      * 103 /MUL recovered spontaneously without medical intervention. CONCLUSION AND
      CLINICAL IMPORTANCE: The number of dose delays was minimized with a
      prechemotherapy ANC cutoff of 1.5 * 103 /MUL, and the prechemotherapy ANC class
      1.5-1.99 * 103 /MUL was not associated with an increased toxicity. Further
      investigation of an ANC cutoff near 0.75 * 103 /MUL in which to prescribe
      prophylactic antibiotics is indicated.

PMID- 29205495
TI  - The premotor syndrome of cervical dystonia: Disordered processing of salient
      environmental stimuli.

PMID- 29205496
TI  - Critical caring theory and public health nursing advocacy for comprehensive
      sexual health education.
AB  - Public health nurses (PHNs) often work with adolescent populations at risk for
      unplanned pregnancies who do not have access to comprehensive sexual health
      education (CSHE). Evidence-based CSHE can have a significant protective effect on
      adolescent sexual behaviors. This article applies critical caring theory to
      public health nursing advocacy for CSHE. Critical caring theory defines the
      social justice work of PHNs as an expression of their caring as nurses. The lack
      of CSHE in schools for adolescents is a social justice issue, and PHNs can be
      important advocates. The purpose of this article is to explore how critical
      caring theory can inform public health nursing practice regarding the importance
      of CSHE advocacy with the goal of creating equitable access to CSHE for all
      adolescents.

PMID- 29205497
TI  - The use of preoperative aspirin in cardiac surgery: A systematic review and meta
      analysis.
AB  - BACKGROUND: Despite the fact that aspirin is of benefit to patients following
      coronary artery bypass grafting (CABG), continuation or administration of
      preoperative aspirin before CABG or any cardiac surgical procedure remains
      controversial. Therefore, we performed a systematic review and meta-analysis to
      assess the influence of preoperative aspirin administration on patients
      undergoing cardiac surgery. MATERIALS AND METHODS: Medline database was searched
      using OVID SP interface. Similar searches were performed separately in EMBASE,
      PubMed, and Cochrane Central Registry of Controlled Trials. RESULTS: Twelve
      randomized controlled trials and 28 observational studies met our inclusion
      criteria and were included in the meta-analysis. The use of preoperative aspirin
      in patients undergoing CABG at any dose is associated with reduced early
      mortality as well as a reduced incidence of postoperative acute kidney injury
      (AKI). Low-dose aspirin (<=160 mg/d) is associated with a decreased incidence of
      perioperative myocardial infarction (MI). Administration of preoperative aspirin
      at any dose in patients undergoing cardiac surgery increases postoperative
      bleeding. Despite this effect of preoperative aspirin, it did not increase the
      rates of surgical re-exploration due to excessive postoperative bleeding nor did
      it increase the rates of packed red blood cell transfusions (PRBC) when
      preoperative low-dose aspirin (<=160 mg/d) was administered. CONCLUSIONS:
      Preoperative aspirin increases the risk for postoperative bleeding. However, this
      did not result in an increased need for chest re-exploration and did not increase
      the rates of PRBC transfusion when preoperative low-dose (<=160 mg/d) aspirin was
      administered. Aspirin at any dose is associated with decreased mortality and AKI
      and low-dose aspirin (<=160 mg/d) decreases the incidence of perioperative MI.

PMID- 29205498
TI  - Efficacy of topical 5-aminosalicylate monotherapy in patients with ulcerative
      proctitis with skip inflammation.
AB  - BACKGROUND AND AIM: In some patients with ulcerative proctitis (UP), skip
      inflammation is noted in the right side of the colon, but little is known about
      its clinical course. The aim of this study was to evaluate the clinical course of
      UP with skip inflammation and the efficacy of topical 5-aminosalicylate (5-ASA)
      monotherapy. METHODS: This study reviewed the data of 388 patients with an
      initial diagnosis of UP from January 2005 to October 2015. This study matched
      each UP patient with skip inflammation 1:2 with controls who had UP without skip
      inflammation; to reduce bias, this study matched the controls with the cases by
      age, gender, and initial disease activity. RESULTS: During the follow-up period
      (median: 69.5 months), the overall progression rates for the control group (n =
      192) and the skip inflammation group (n = 96) were 24.0% and 32.9% at 10 years,
      respectively (log-rank P = 0.71). In the skip inflammation group, the progression
      rates were not significantly different between the 5-ASA combination group and
      the topical group, 33.4% and 26.6% at 10 years, respectively (log-rank P = 0.96).
      The overall acute exacerbation rates for the control and skip inflammation groups
      were 17.2% and 26.8% at 10 years, respectively (log-rank P = 0.68). In the skip
      inflammation group, the exacerbation rates were also not significantly different
      between the combination and topical treatment groups, 26.6% and 23.6% at 10
      years, respectively (log-rank P = 0.88). CONCLUSION: The clinical course of UP
      with skip inflammation was not different from that of typical UP, and topical 5
      ASA monotherapy for maintaining remission was as effective as 5-ASA combination
      therapy irrespective of the presence of skip lesions.

PMID- 29205499
TI  - Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with
      Atrial Fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) usually is associated with a rapid
      ventricular rate. The optimal heart rate (HR) during AF is unknown.
      HYPOTHESIS/OBJECTIVES: Heart rate affects survival in dogs with chronic AF.
      ANIMALS: Forty-six dogs with AF and 24-hour ambulatory recordings were evaluated.
      METHODS: Retrospective study. Holter-derived HR variables were analyzed as
      follows: mean HR (meanHR, 24-hour average), minimum HR (minHR, 1-minute average),
      maximum HR (maxHR, 1-minute average). Survival times were recorded from the time
      of presumed adequate rate control. The primary endpoint was all-cause mortality.
      Cox proportional hazards analysis identified variables independently associated
      with survival; Kaplan-Meier survival analysis estimated the median survival time
      of dogs with meanHR <125 bpm versus >=125 bpm. RESULTS: All 46 dogs had
      structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46
      received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median
      time to all-cause death was 524 days (Interquartile range (IQR), 76-1,037 days).
      MeanHR was 125 bpm (range, 62-203 bpm), minHR was 82 bpm (range, 37-163 bpm),
      maxHR was 217 bpm (range, 126-307 bpm). These were significantly correlated with
      all-cause and cardiac-related mortality. For every 10 bpm increase in meanHR, the
      risk of all-cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17
      1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was
      significantly longer (1,037 days; range, 524-open) than meanHR >=125 bpm (n = 23;
      105 days; range, 67-267 days; P = 0.0012). Mean HR was independently associated
      with all-cause and cardiovascular mortality (P < 0.003). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Holter-derived meanHR affects survival in dogs with AF. Dogs with
      meanHR <125 bpm lived longer than those with meanHR >= 125 bpm.

PMID- 29205501
TI  - Predictive testing and clinical trials in Huntington's disease: An ethical
      analysis.

PMID- 29205500
TI  - A functional SNP in the 3'-UTR of TAP2 gene interacts with microRNA hsa-miR-1270
      to suppress the gene expression.
AB  - The transporter associated with antigen processing 2 (TAP2) is involved in the
      development of multidrug resistance and the etiology of immunological diseases.
      In this study, we investigated whether the expression of TAP2 can be perturbed by
      single nucleotide polymorphisms (SNPs) located in 3'-untranslated region (3'-UTR)
      of the gene via interactions with microRNAs. Using a series of in silico assays,
      we selected the candidate microRNAs (miRNAs) with the potential to interact with
      functional SNPs of TAP2. The SNP rs241456-located in the 3'-UTR of TAP2-resides
      in a potential binding site for hsa-miR-1270 and hsa-miR-620. HEK 293 cells, from
      a human kidney cell line, were used to characterize the extent of binding of
      miRNAs to each polymorphic allele of the SNP by a luciferase reporter gene assay.
      RNA electrophoretic mobility shift assays were used to evaluate the interaction
      between the miRNAs and each allele sequence of the SNP. We found that hsa-miR
      1270 inhibited luciferase activity by binding to the T allele of the SNP in an
      allele-specific manner. A negative correlation was also found between the
      expression of hsa-miR-1270 and the T allele of the SNP in kidney tissues. Our
      findings support the hypothesis that hsa-miR-1270 suppresses the production of
      TAP2 by binding to this SNP in the 3'-UTR of this gene. Environ. Mol. Mutagen.
      59:134-143, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29205502
TI  - Intraoperative thermographic imaging to assess myocardial distribution of Del
      Nido cardioplegia.
AB  - We describe the intraoperative non-invasive use of an infrared (IR) camera to
      monitor Del Nido cardioplegia delivery in patients undergoing cardiac surgery.
      Thermal pictures were taken pre- and post-cardioplegia and at timed points after
      arrest, and compared to readings from a transseptal temperature probe. There was
      good concordance between the transseptal probe and the IR camera temperature
      readings. This non-invasive technique, which assesses cardioplegic distribution,
      may help to determine when additional doses of Del Nido cardioplegia are required
      during periods of cardioplegic arrest.

PMID- 29205504
TI  - Exploring the effects of sparse restraints on protein structure prediction.
AB  - One of the main barriers to accurate computational protein structure prediction
      is searching the vast space of protein conformations. Distance restraints or
      inter-residue contacts have been used to reduce this search space, easing the
      discovery of the correct folded state. It has been suggested that about 1 contact
      for every 12 residues may be sufficient to predict structure at fold level
      accuracy. Here, we use coarse-grained structure-based models in conjunction with
      molecular dynamics simulations to examine this empirical prediction. We generate
      sparse contact maps for 15 proteins of varying sequence lengths and topologies
      and find that given perfect secondary-structural information, a small fraction of
      the native contact map (5%-10%) suffices to fold proteins to their correct native
      states. We also find that different sparse maps are not equivalent and we make
      several observations about the type of maps that are successful at such structure
      prediction. Long range contacts are found to encode more information than shorter
      range ones, especially for alpha and alphabeta-proteins. However, this
      distinction reduces for beta-proteins. Choosing contacts that are a consensus
      from successful maps gives predictive sparse maps as does choosing contacts that
      are well spread out over the protein structure. Additionally, the folding of
      proteins can also be used to choose predictive sparse maps. Overall, we conclude
      that structure-based models can be used to understand the efficacy of structure
      prediction restraints and could, in future, be tuned to include specific force
      field interactions, secondary structure errors and noise in the sparse maps.

PMID- 29205503
TI  - Gallbladder Mucocele: Variables Associated with Outcome and the Utility of
      Ultrasonography to Identify Gallbladder Rupture in 219 Dogs (2007-2016).
AB  - BACKGROUND: Gallbladder mucocele (GBM) is an increasingly recognized extrahepatic
      biliary disease in dogs. OBJECTIVES: To investigate cases of GBM and identify
      variables associated with survival and the sensitivity and specificity of
      ultrasonography to identify gallbladder rupture. ANIMALS: Two hundred and
      nineteen client-owned dogs with GBM. METHODS: Multicenter, retrospective study of
      dogs with GBM, presented from January 2007 to November 2016 to 6 academic
      veterinary hospitals in the United States. Interrogation of hospital databases
      identified all cases with the inclusion criteria of a gross and histopathologic
      diagnosis of GBM after cholecystectomy and intraoperative bacteriologic cultures
      of at least 1 of the following: gallbladder wall, gallbladder contents, or
      abdominal effusion. RESULTS: Two hundred and nineteen dogs fulfilled the
      inclusion criteria. Dogs with GBM and gallbladder rupture with bile peritonitis
      at the time of surgery were 2.7 times more likely to die than dogs without
      gallbladder rupture and bile peritonitis (P = 0.001; 95% confidence interval
      [CI], 1.50-4.68; n = 41). No significant associations were identified between
      survival and positive bacteriologic cultures, antibiotic administration, or time
      (days) from ultrasonographic identification of GBM to the time of surgery. The
      sensitivity, specificity, positive, and negative likelihood ratios for
      ultrasonographic identification of gallbladder rupture were 56.1% (95% CI, 39.9
      71.2), 91.7% (95% CI, 85.3-95.6), 6.74, and 0.44, respectively. CONCLUSION AND
      CLINICAL IMPORTANCE: Dogs in our study with GBM and intraoperative evidence of
      gallbladder rupture and bile peritonitis had a significantly higher risk of
      death. Additionally, abdominal ultrasonography had low sensitivity for
      identification of gallbladder rupture.

PMID- 29205505
TI  - New drugs for Parkinson's disease: The regulatory and clinical development
      pathways in the United States.

PMID- 29205506
TI  - Systematic review and meta-analysis on the efficacy and tolerability of
      mirabegron for the treatment of storage lower urinary tract symptoms/overactive
      bladder: Comparison with placebo and tolterodine.
AB  - A systematic review and meta-analysis was carried out to evaluate the efficacy
      and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower
      urinary tract symptoms/overactive bladder in comparison with a placebo and
      tolterodine 4 mg. A total of 491 articles were collected and eight randomized
      studies were identified as eligible for this meta-analysis. Overall, eight trials
      were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both
      doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated
      with the reduction of incontinence episodes per 24 h, reduction of mean number of
      micturitions per 24 h, increase of voided volume and reduction of urgency
      episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron
      100 mg were associated with a significant reduction of nocturia episodes when
      compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more
      effective than a placebo in the reduction of nocturia episodes. Furthermore,
      mirabegron 50 mg showed a slightly, but significantly, better efficacy than
      tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and
      mirabegron 100 mg shared the same risk of overall treatment-emergent adverse
      events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a
      significantly greater risk than the placebo. However, mirabegron 100 mg showed a
      slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08)
      and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective
      treatment for patients with storage lower urinary tract symptoms/overactive
      bladder, providing a reduction of incontinence, urgency and frequency; an
      improvement of voided volume with a slight, but statistically, significant
      improvement of nocturia; with a good safety profile. These findings should be
      considered for the treatment planning of patients with storage lower urinary
      tract symptoms/overactive bladder.

PMID- 29205507
TI  - Current status of holmium laser enucleation of the prostate.
AB  - There are several options for the surgical management of benign prostatic
      hyperplasia representatively from transurethral resection of the prostate.
      Holmium laser enucleation of the prostate is one of those options, and many
      institutions and urologists have initiated this technique, and most of them have
      accomplished better outcomes compared with transurethral resection of the
      prostate. In contrast to transurethral resection of the prostate, which requires
      a similar procedure to transurethral resection of bladder tumors, holmium laser
      enucleation of the prostate requires a special surgical technique: enucleation
      and morcellation with around 10 years' history of experience, even in Japan. The
      present review introduces the current status of holmium laser enucleation of the
      prostate, so that it surely contributes to the knowledge of International Journal
      of Urology readers who could be experienced surgeons or beginners as well.

PMID- 29205508
TI  - Aberrant methylation of mutL homolog 1 is associated with increased risk of non
      small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is a common malignant tumor. DNA
      hypermethylation in the promoter region has been served as a potential molecular
      marker for several tumors. The goal of the current study was to assess the
      diagnostic ability of mutL homolog 1 (MLH1) promoter methylation in NSCLC.
      METHODS: A total of 111 NSCLC patients' paired tissue samples were obtained to
      explore the association between MLH1 promoter methylation and NSCLC by
      methylation-specific polymerase chain reaction (MSP) method. Public databases
      including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were
      used to verify our findings. RESULTS: Our results showed a significantly higher
      MLH1 methylation frequency in tumor tissue samples than their paired adjacent
      tissues (P = .008). ROC curve indicated that MLH1MSP assay was a sensitive but
      not a specific method in the diagnosis for NSCLC (sensitivity = 0.964,
      specificity = 0.135, AUC = 0.550). And the association between the methylation
      level and clinical characteristics has no statistical significance. TCGA cohort
      evinced a higher methylation probability in tumor group compared with nontumor
      group (the mean beta value: -0.449 [-0.467, -0.437] vs -0.466 [-0.472, -0.437], P
      = .011), which was consistent with our results. Meanwhile, an inverse correlation
      between MLH1 methylation and MLH1 expression was detected in TCGA and GEO
      databases. CONCLUSIONS: The MSP method for MLH1 methylation was a sensitive but
      not a specific diagnostic method for NSCLC.

PMID- 29205510
TI  - Correction of cortriatriatum sinister with classical Raghib's complex using an
      extracardiac conduit.
AB  - We present a 32-year-old patient with cortriatriatum sinister with Raghib's
      complex (a left persistent superior vena cava draining into the left atrium with
      an absent coronary sinus and an atrial septal defect [ASD]) who underwent
      successful surgical correction with excision of the cortriatriatum, closure of
      the ASD, and establishing the drainage of the persistent left superior vena cava
      to the right atrium via interposition of an extracardiac 13-mm ringed
      polytetrafluoroethylene conduit.

PMID- 29205511
TI  - Mechanistic insights into topical tacrolimus for the treatment of atopic
      dermatitis.
AB  - More than 15 years have passed since the clinical launch of topical tacrolimus
      for the treatment of atopic dermatitis. Its efficacy and safety have been clearly
      demonstrated in many global and domestic short-term and long-term clinical
      trials. Although the prolonged external application of steroids causes many
      adverse reactions including cutaneous atrophy, no such reactions occur with the
      use of topical tacrolimus. Therefore, the therapeutic guidelines recommend a
      combined topical treatment with tacrolimus and steroids. Tacrolimus is a potent
      immunosuppressant. However, recent studies have revealed its diverse action on
      the cardinal pathomechanisms of atopic dermatitis. In this review, we summarize
      the mechanistic role of tacrolimus in various aspects of allergic inflammation
      including mast cell activation, innate allergic response, pruritus, sensory nerve
      activation, and skin barrier dysfunction.

PMID- 29205509
TI  - Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among
      biomarkers and Parkinson's disease Features.
AB  - OBJECTIVE: Examine relationships among neurodegenerative biomarkers and PD motor
      and nonmotor symptoms. BACKGROUND: CSF alpha-synuclein is decreased in PD versus
      healthy controls, but whether plasma and saliva alpha-synuclein differentiate
      these groups is controversial. Correlations of alpha-synuclein among biofluids
      (CSF, plasma, saliva) or biomarkers (eg, beta-amyloid, tau [total,
      phosphorylated]) are not fully understood. The relationships of these biomarkers
      with PD clinical features remain unclear. METHODS: BioFIND, a cross-sectional,
      observational study, examines clinical and biomarker characteristics in moderate
      advanced PD and matched healthy controls. We compared alpha-synuclein
      concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of
      CSF biomarkers and MDS-UPDRS, motor phenotype, MoCA, and rapid eye movement sleep
      behavior disorder questionnaire scores in PD were examined. RESULTS: CSF alpha
      synuclein was lower in PD versus controls (P = .01), controlling for age, gender,
      and education. Plasma and saliva alpha-synuclein did not differ between PD and
      controls, and alpha-synuclein did not significantly correlate among biofluids.
      CSF beta-amyloid1-42 was lower in PD versus controls (P < .01), and correlated
      weakly with MoCA recall scores (r = 0.23, P = .02). CSF alpha-synuclein was lower
      in the postural instability/gait difficulty phenotype than other motor phenotypes
      (P < .01). No CSF biomarkers predicted or correlated with total motor or rapid
      eye movement sleep behavior disorder scores. CSF alpha-synuclein correlated with
      beta-amyloid1-42 , total-tau, and phosphorylated-tau (r = 0.41, 0.81, 0.43,
      respectively; Ps < .001). CONCLUSION: Lower CSF alpha-synuclein is associated
      with diagnosis and motor phenotype in moderate-advanced PD. Plasma and saliva
      alpha-synuclein neither correlate with CSF alpha-synuclein, nor distinguish PD
      from controls. CSF beta-amyloid1-42 remains a potential biomarker for cognitive
      impairment in PD. (c) 2017 The Authors. Movement Disorders published by Wiley
      Periodicals, Inc. on behalf of International Parkinson and Movement Disorder
      Society.

PMID- 29205512
TI  - Self-perceptions of aging mediate the longitudinal relationship of hopelessness
      and depressive symptoms.
AB  - OBJECTIVES: The purpose of the current study was to examine the hypothesis that
      the prospective relationship between hopelessness and depressive symptoms is
      mediated by self-perceptions of aging. METHODS: Data from 3 waves of the US
      Health and Retirement Study (2008, 2012, and 2014) were used (N = 4606; age M =
      65.3, 55.5% female). In mediation analyses, hopelessness in 2008 was the
      independent variable, self-perceptions of aging in 2012 were the mediator, and
      depressive symptoms in 2014 were the outcome variable. RESULTS: After controlling
      for covariates, hopelessness in 2008 was an independent predictor of self
      perceptions of aging in 2012 (beta = -.10, P < .001), and self-perceptions of
      aging in 2012 was an independent predictor of depressive symptoms in 2014 (beta =
      -.41, P < .001). Hopelessness in 2008 showed both direct (beta = .09, P < .001)
      and indirect (beta = .03, P < .001) effects on depressive symptoms in 2014,
      indicating partial mediation by change in self-perceptions of aging. CONCLUSIONS:
      As hypothesized, change in self-perceptions of aging partially mediated the
      relationship of hopelessness with depressive symptoms 6 years later. Findings are
      consistent with a conceptualization of hopelessness as broad negative
      expectations about the future that may contribute to negative self-perceptions of
      aging and subsequent changes in depressive symptoms. Reducing hopelessness,
      increasing hope, and improving self-perceptions of aging have potential to reduce
      and prevent depressive symptoms for older adults. Future research should examine
      the mechanisms of these interrelationships and other aging outcomes.

PMID- 29205513
TI  - Observations on the inconsistency of dermatome maps and its effect on knowledge
      and confidence in clinical students.
AB  - Dermatomes are an important component of medical curricula and clinical practice.
      In addition to the intrinsic complexity of dermatome maps, their discrepancies in
      the literature make their learning among students even more difficult. These
      discrepancies are particularly evident in the lower deltoid ("regimental badge"
      area) and upper back. The aims of our study were firstly to identify and compare
      published versions of the dermatome map focusing on depictions of the "regimental
      badge" area and upper back, secondly to assess the perceived confidence and
      knowledge of dermatomes among medical students, and finally to create and
      introduce a simplified dermatome map. For the first part of the study, depictions
      of dermatome maps that included the "regimental badge" area and upper back in
      webpages and books were compared. For the second part, a dermatome exercise was
      given to 177 medical students who were asked to draw and label the dermatomes on
      blank figures. A total of 45 sources depicting dermatomes of the "regimental
      badge" area and upper back were included in the study and showed significant
      discrepancies in both areas. In the dermatome exercise, the mean perceived
      confidence was 3.64 +/- 1.58 (scale 1-10). Based on our pre-set assessment
      criteria, upper limb, lower limb, nipple, umbilicus, and perineum dermatomes were
      labeled correctly by 57.1%, 43.5%, 52.6%, 60%, and 75.7% students, respectively.
      In light of our results, we propose a map of autonomous regions of clinically
      relevant dermatomes that can be used instead of whole dermatome maps for teaching
      purposes. Clin. Anat. 31:293-300, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29205514
TI  - Acute kidney injury impact on inpatient mortality in Clostridium difficile
      infection: A national propensity-matched study.
AB  - BACKGROUND AND AIM: Acute kidney injury (AKI) is used as a marker of severity in
      Clostridium difficile infection (CDI) patients. We estimated the true effect of
      AKI in inpatient mortality of CDI patients, as there are no large-scale,
      population-based, propensity-matched studies evaluating AKI's effect in this
      patient cohort. METHODS: A retrospective observational study utilizing the
      National Inpatient Sample from years 2003 to 2012, including all adults with CDI,
      excluding cases missing data on age, inpatient mortality or gender. Trends and
      CDI-related complications as mortality predictors were assessed using survey
      weighted multivariable regression. We estimated AKI's independent effect by
      propensity-matching, post-stratifying by chronic kidney disease status, allowing
      for multiple comorbidity adjustment. RESULTS: A total of 2 859 599 patients with
      CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI
      prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher
      (18.2%). In multivariable regression, AKI was associated with higher mortality
      (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02-3.30; P < 0.001),
      while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95%
      CI: 1.79-1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate
      of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing
      hospitalizations, mortality over the study period decreased to 7.2% (2012) from
      9.0% (2003); P-trend < 0.001. CONCLUSION: Hospital admissions of patients with
      CDI and concomitant AKI are increasing, but their inpatient mortality has
      improved over the study period. AKI is a significant contributor to mortality,
      independently of other comorbidities, complications, and hospital
      characteristics, emphasizing the need for early diagnosis and aggressive
      management in such patients.

PMID- 29205515
TI  - Yoga training modulates adipokines in adults with high-normal blood pressure and
      metabolic syndrome.
AB  - Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular
      diseases. Our previous study indicated that people with MetS showed a decrease in
      waist circumference and a decreasing trend in blood pressure after 1-year yoga.
      This study investigated the effect of yoga on MetS people with high-normal blood
      pressure by exploring modulations in proinflammatory adipokines (leptin,
      chemerin, visfatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti
      inflammatory adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals
      aged 57.6 +/- 9.1 years with MetS and high-normal blood pressure were randomly
      assigned to control (n = 45) and yoga groups (n = 52). Participants in the
      control group were not given any intervention but were contacted monthly to
      monitor their health status. Participants in the yoga group underwent a yoga
      training program with three 1-hour yoga sessions weekly for 1 year. The
      participants' sera were harvested and assessed for adipokines. Generalized
      estimating equation (GEE) was used to examine the interaction effect between 1
      year time (pre vs post), and intervention (control vs yoga). GEE analyses
      revealed significant interaction effects between 1-year time and yoga
      intervention for the decreases in leptin and chemerin and the increase in
      adiponectin concentration in the sera examined. These results demonstrated that 1
      year yoga training decreased proinflammatory adipokines and increased anti
      inflammatory adipokine in adults with MetS and high-normal blood pressure. These
      findings support the beneficial role of yoga in managing MetS by favorably
      modulating adipokines.

PMID- 29205516
TI  - A tripartite mode of action approach for investigating the impact of aneugens on
      tubulin polymerization.
AB  - Chemical-induced disruption of the cellular microtubule network is one key
      mechanism of aneugenicity. Since recent data indicate that genotoxic effects of
      aneugens show nonlinear dose-response relationships, margins of safety can be
      derived with the ultimate goal to perform a risk assessment for the support of
      drug development. Furthermore, microtubule-interacting compounds are widely used
      for cancer treatment. While there is a need to support the risk assessment of
      tubulin-interacting chemicals using reliable mechanistic assays, no standard
      assays exist to date in regulatory genotoxicity testing for the distinction of
      aneugenic mechanisms. Recently reported methods exclusively rely on either
      biochemical, morphological, or cytometric endpoints. Since data requirements for
      the diverse fields of application of those assays differ strongly, the use of
      multiple assays for a correct classification of aneugens is ideal. We here report
      a tripartite mode of action approach comprising a cell-free biochemical
      polymerization assay and the cell-based methods cellular imaging and flow
      cytometry. The biochemical assay measures tubulin polymerization over time
      whereas the two cell-based assays quantify tubulin polymer mass. We herein show
      that the flow cytometric method yielded IC50 values for tubulin destabilizers and
      EC50 values for tubulin stabilizers as well as cell cycle information. In
      contrast, cellular imaging complemented these findings with characteristic
      morphological patterns. Biochemical analysis yielded kinetic information on
      tubulin polymerization. This multiplex approach is able to create holistic effect
      profiles which can be individually customized to the research question with
      regard to quality, quantity, usability, and economy. Environ. Mol. Mutagen.
      59:188-201, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29205517
TI  - Within-day energy deficiency and reproductive function in female endurance
      athletes.
AB  - We aimed to estimate and compare within-day energy balance (WDEB) in athletes
      with eumenorrhea and menstrual dysfunction (MD) with similar 24-hour energy
      availability/energy balance (EA/EB). Furthermore, to investigate whether within
      day energy deficiency is associated with resting metabolic rate (RMR), body
      composition, S-cortisol, estradiol, T3 , and fasting blood glucose. We reanalyzed
      7-day dietary intake and energy expenditure data in 25 elite endurance athletes
      with eumenorrhea (n = 10) and MD (n = 15) from a group of 45 subjects where those
      with disordered eating behaviors (n = 11), MD not related to low EA (n = 5), and
      low dietary record validity (n = 4) had been excluded. Besides gynecological
      examination and disordered eating evaluation, the protocol included RMR
      measurement; assessment of body composition by dual-energy X-ray absorptiometry,
      blood plasma analysis, and calculation of WDEB in 1-hour intervals. Subjects with
      MD spent more hours in a catabolic state compared to eumenorrheic athletes; WDEB
      < 0 kcal: 23.0 hour (20.8-23.4) vs 21.1 hour (4.7-22.3), P = .048; WDEB < -300
      kcal: 21.8 hour (17.8-22.4) vs 17.6 hour (3.9-20.9), P = .043, although similar
      24-hour EA: 35.6 (11.6) vs 41.3 (12.7) kcal/kg FFM/d, (P = .269), and EB: -659
      (551) vs -313 (596) kcal/d, (P = .160). Hours with WDEB <0 kcal and <-300 kcal
      were inversely associated with RMRratio (r = -.487, P = .013, r = -.472, P =
      .018), and estradiol (r = -.433, P = .034, r = -.516, P = .009), and positively
      associated with cortisol (r = .442, P = .027, r = .463, P = .019). In conclusion,
      although similar 24-hour EA/EB, the reanalysis revealed that MD athletes spent
      more time in a catabolic state compared to eumenorrheic athletes. Within-day
      energy deficiency was associated with clinical markers of metabolic disturbances.

PMID- 29205519
TI  - Polar Elastomers as Novel Materials for Electromechanical Actuator Applications.
AB  - Dielectric elastomer actuators are stretchable capacitors capable of a musclelike
      actuation when charged. They will one day be used to replace malfunctioning
      muscles supposing the driving voltage can be reduced below 24 V. This focus here
      is on polar dielectric elastomers and their behavior under an electric field.
      Emphasis is placed on all the features that are correlated with the molecular
      structure, its synthetic realization, and its impact on properties. Regarding the
      polymer class, the focus, to some degree, is on polysiloxanes because of their
      attractively low glass transition temperatures. This enables introduction of
      highly polar groups to the backbone while maintaining soft elastic properties.
      The goal is to provide a few guidelines for future research in this emerging
      field that may be useful for those considering entering this fascinating
      endeavor. Because of the large number of materials available, a few restrictions
      in the selection have to be applied.

PMID- 29205518
TI  - Therapeutic and prognostic significance of PARP-1 in advanced mycosis fungoides
      and Sezary syndrome.
AB  - While mycosis fungoides (MF) is typically an indolent malignancy, it may
      infrequently undertake an aggressive course. We used proteomic analyses to
      identify a biomarker of the aggressive course of MF. Results of this
      investigation demonstrated that PARP-1, heat-shock protein family A (Hsp70)
      member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA helicase
      (DDX17) and the alpha-isoform of lamina-associated polypeptide 2 (TMPO) had
      higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1
      was overexpressed in patients with early stage of MF who developed later an
      aggressive disease. PARP-1 was evaluated as a new target for therapy,
      demonstrating the selective dose-dependent cytotoxic effect of PARP inhibitors on
      Sezary cells in comparison with non-malignant lymphocytes. In conclusion, we
      believe that PARP-1 may serve not only as a biomarker at initial biopsies for a
      disease that may become aggressive but also as a new therapeutic target of
      advanced MF and Sezary syndrome.

PMID- 29205520
TI  - Advanced Biomass-Derived Electrocatalysts for the Oxygen Reduction Reaction.
AB  - Recent progress in advanced nanostructures synthesized from biomass resources for
      the oxygen reduction reaction (ORR) is reviewed. The ORR plays a significant role
      in the performance of numerous energy-conversion devices, including low
      temperature hydrogen and alcohol fuel cells, microbial fuel cells, as well as
      metal-air batteries. The viability of such fuel cells is strongly related to the
      cost of the electrodes, especially the cathodic ORR electrocatalyst. Hence,
      inexpensive and abundant plant and animal biomass have become attractive options
      to obtain electrocatalysts upon conversion into active carbon. Bioresource
      selection and processing criteria are discussed in light of their influence on
      the physicochemical properties of the ORR nanostructures. The resulting
      electrocatalytic activity and durability are introduced and compared to those
      from conventional Pt/C-based electrocatalysts. These ORR catalysts are also
      active for oxygen or hydrogen evolution reactions.

PMID- 29205522
TI  - Acoustic Fabrication via the Assembly and Fusion of Particles.
AB  - Acoustic assembly promises a route toward rapid parallel fabrication of whole
      objects directly from solution. This study reports the contact-free and maskless
      assembly, and fixing of silicone particles into arbitrary 2D shapes using
      ultrasound fields. Ultrasound passes through an acoustic hologram to form a
      target image. The particles assemble from a suspension along lines of high
      pressure in the image due to acoustic radiation forces and are then fixed
      (crosslinked) in a UV-triggered reaction. For this, the particles are loaded with
      a photoinitiator by solvent-induced swelling. This localizes the reaction and
      allows the bulk suspension to be reused. The final fabricated parts are
      mechanically stable and self-supporting.

PMID- 29205524
TI  - Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf
      region: A case and review.
AB  - Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly
      neurotropic dematiaceous fungi. Although rare, this infection occurs especially
      among immunocompetent patients, and the clinical symptoms are often misdiagnosed
      as a cerebral tumour or bacterial brain abscess. The appropriate diagnosis and
      therapy of cerebral infections by melanized fungi are very challenging if they
      are caused by mysterious fungi with unknown ecological niche. We reported the
      second case of cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in
      Iran and the first culture-confirmed case. In this report, the differential
      diagnosis and histopathological findings are discussed and a review of the
      literature is provided.

PMID- 29205523
TI  - Melatonin reduces apoptotic cells, SOD2 and HSPB1 and improves the in vitro
      production and quality of bovine blastocysts.
AB  - Effects of adding different concentrations of melatonin (10-7 , 10-9 and 10-11 
      M) to maturation (Experiment 1; Control, IVM + 10-7 , IVM + 10-9 , IVM + 10-11 )
      and culture media (Experiment 2; Control, IVC + 10-7 , IVC + 10-9 , IVC + 10-11 )
      were evaluated on in vitro bovine embryonic development. The optimal
      concentration of melatonin (10-9  M) from Experiments 1-2 was tested in both
      maturation and/or culture media of Experiment 3 (Control, IVM + 10-9 , IVC + 10-9
      , IVM/IVC + 10-9 ). In Experiment 1, maturated oocytes from Control and IVM + 10
      9 treatments showed increased glutathione content, mitochondrial membrane
      potential and percentage of Grade I blastocysts (40.6% and 43%, respectively). In
      Experiment 2, an increase in the percentage of Grade I blastocysts was detected
      in IVC + 10-7 (43.5%; 56.7%) and IVC + 10-9 (47.4%; 57.4%). Moreover, a lower
      number and percentage of apoptotic cells in blastocysts were observed in the IVC
      + 10-9 group compared to Control (3.8 +/- 0.6; 3.6% versus 6.1 +/- 0.6; 5.3%). In
      Experiment 3, the IVC + 10-9 treatment increased percentage of Grade I
      blastocysts with a lower number of apoptotic cells compared to IVM/IVC + 10-9
      group (52.6%; 3.0 +/- 0.5 versus 46.0%; 5.4 +/- 1.0). The IVC + 10-9 treatment
      also had a higher mRNA expression of antioxidant gene (SOD2) compared to the
      Control, as well as the heat shock protein (HSPB1) compared to the IVM + 10-9 .
      Reactive oxygen species production was greater in the IVM/IVC + 10-9 treatment
      group. In conclusion, the 10-9  M concentration of melatonin and the in vitro
      production phase in which it is used directly affected embryonic development and
      quality.

PMID- 29205525
TI  - Hole-Transfer Dependence on Blend Morphology and Energy Level Alignment in
      Polymer: ITIC Photovoltaic Materials.
AB  - Bulk-heterojunction organic photovoltaic materials containing nonfullerene
      acceptors (NFAs) have seen remarkable advances in the past year, finally
      surpassing fullerenes in performance. Indeed, acceptors based on
      indacenodithiophene (IDT) have become synonymous with high power conversion
      efficiencies (PCEs). Nevertheless, NFAs have yet to achieve fill factors (FFs)
      comparable to those of the highest-performing fullerene-based materials. To
      address this seeming anomaly, this study examines a high efficiency IDT-based
      acceptor, ITIC, paired with three donor polymers known to achieve high FFs with
      fullerenes, PTPD3T, PBTI3T, and PBTSA3T. Excellent PCEs up to 8.43% are achieved
      from PTPD3T:ITIC blends, reflecting good charge transport, optimal morphology,
      and efficient ITIC to PTPD3T hole-transfer, as observed by femtosecond transient
      absorption spectroscopy. Hole-transfer is observed from ITIC to PBTI3T and
      PBTSA3T, but less efficiently, reflecting measurably inferior morphology and
      nonoptimal energy level alignment, resulting in PCEs of 5.34% and 4.65%,
      respectively. This work demonstrates the importance of proper morphology and
      kinetics of ITIC -> donor polymer hole-transfer in boosting the performance of
      polymer:ITIC photovoltaic bulk heterojunction blends.

PMID- 29205528
TI  - Corrigendum.

PMID- 29205526
TI  - Alumina-Supported CoFe Alloy Catalysts Derived from Layered-Double-Hydroxide
      Nanosheets for Efficient Photothermal CO2 Hydrogenation to Hydrocarbons.
AB  - A series of novel CoFe-based catalysts are successfully fabricated by hydrogen
      reduction of CoFeAl layered-double-hydroxide (LDH) nanosheets at 300-700  degrees
      C. The chemical composition and morphology of the reaction products (denoted
      herein as CoFe-x) are highly dependent on the reduction temperature (x). CO2
      hydrogenation experiments are conducted on the CoFe-x catalysts under UV-vis
      excitation. With increasing LDH-nanosheet reduction temperature, the CoFe-x
      catalysts show a progressive selectivity shift from CO to CH4 , and eventually to
      high-value hydrocarbons (C2+ ). CoFe-650 shows remarkable selectivity toward
      hydrocarbons (60% CH4 , 35% C2+ ). X-ray absorption fine structure, high
      resolution transmission electron microscopy, Mossbauer spectroscopy, and density
      functional theory calculations demonstrate that alumina-supported CoFe-alloy
      nanoparticles are responsible for the high selectivity of CoFe-650 for C2+
      hydrocarbons, also allowing exploitation of photothermal effects. This study
      demonstrates a vibrant new catalyst platform for harnessing clean, abundant solar
      energy to produce valuable chemicals and fuels from CO2 .

PMID- 29205527
TI  - A Novel Acoustomicrofluidic Nebulization Technique Yielding New Crystallization
      Morphologies.
AB  - A novel acoustic microfluidic nebulization platform is demonstrated, which, due
      to its unique ability to access intermediate evaporation rate regimes
      significantly faster than that in slow solvent evaporation but considerably below
      that achieved in spray drying, is capable of producing novel crystal morphologies
      that have yet to be reported in both model inorganic and organic systems. In
      addition, the potential for simultaneously encapsulating single crystals within a
      biodegradable polymeric coating in a single simultaneous step together with the
      crystallization process as the solvent evaporates during nebulization is briefly
      shown. The platform not only has the potential to be highly scalable by employing
      a large number of these low-cost miniature devices in parallel to achieve
      industrially relevant particle production rates, but could also be advantageous
      over conventional spray drying in terms of energy utilization, given the
      tremendous efficiency associated with the high-frequency ultrasonic microdevice
      as well as its ambient temperature operation.

PMID- 29205531
TI  - Alkenyl and Aryl Peroxides.
AB  - Alkenyl and aryl peroxides are a special class of organic peroxides. Under
      ambient conditions, they are usually short-lived, rapidly decomposing into
      radicals by homolytic O-O bond cleavage. They play an important role in the
      chemistry of the lower atmosphere, where they are formed through ozonolysis of
      alkenes. In the dark, this pathway is considered the major source of hydroxyl
      radicals, the "detergent of the atmosphere". In solution, alkenyl and aryl
      peroxides can be formed by various methods and their decomposition can be
      harnessed synthetically. For example, reactions involving alkenyl peroxides can
      be used to introduce ketones through radical additions, and nucleophilic aromatic
      substitution reactions generating aryl peroxides have been used to synthesize
      phenols. The radicals can also initiate radical polymerization reactions or chain
      reactions and mediate oxidative coupling by C-H bond functionalization. Knowledge
      of their chemistry could be helpful for projects generating or utilizing
      peroxides.

PMID- 29205532
TI  - 3D Printing of Living Responsive Materials and Devices.
AB  - 3D printing has been intensively explored to fabricate customized structures of
      responsive materials including hydrogels, liquid-crystal elastomers, shape-memory
      polymers, and aqueous droplets. Herein, a new method and material system capable
      of 3D-printing hydrogel inks with programed bacterial cells as responsive
      components into large-scale (3 cm), high-resolution (30 MUm) living materials,
      where the cells can communicate and process signals in a programmable manner, are
      reported. The design of 3D-printed living materials is guided by quantitative
      models that account for the responses of programed cells in printed
      microstructures of hydrogels. Novel living devices are further demonstrated,
      enabled by 3D printing of programed cells, including logic gates,
      spatiotemporally responsive patterning, and wearable devices.

PMID- 29205533
TI  - Synergism of Rare Earth Trihydrides and Graphite in Lithium Storage: Evidence of
      Hydrogen-Enhanced Lithiation.
AB  - The lithium storage capacity of graphite can be significantly promoted by rare
      earth trihydrides (REH3 , RE = Y, La, and Gd) through a synergetic mechanism.
      High reversible capacity of 720 mA h g-1 after 250 cycles is achieved in YH3 
      graphite nanocomposite, far exceeding the total contribution from the individual
      components and the effect of ball milling. Comparative study on LaH3 -graphite
      and GdH3 -graphite composites suggests that the enhancement factor is 3.1-3.4 Li
      per active H in REH3 , almost independent of the RE metal, which is evident of a
      hydrogen-enhanced lithium storage mechanism. Theoretical calculation suggests
      that the active H from REH3 can enhance the Li+ binding to the graphene layer by
      introducing negatively charged sites, leading to energetically favorable
      lithiation up to a composition Li5 C16 H instead of LiC6 for conventional
      graphite anode.

PMID- 29205534
TI  - Preparation of Microcellular Epoxy Foams through a Limited-Foaming Process: A
      Contradiction with the Time-Temperature-Transformation Cure Diagram.
AB  - 3D cross-linking networks are generated through chemical reactions between
      thermosetting epoxy resin and hardener during curing. The curing degree of epoxy
      material can be increased by increasing curing temperature and/or time. The epoxy
      material must then be fully cured through a postcuring process to optimize its
      material characteristics. Here, a limited-foaming method is introduced for the
      preparation of microcellular epoxy foams (Lim-foams) with improved cell
      morphology, high thermal expansion coefficient, and good compressive properties.
      Lim-foams exhibit a lower glass transition temperature (Tg ) and curing degree
      than epoxy foams fabricated through free-foaming process (Fre-foams).
      Surprisingly, however, the Tg of Lim-foams is unaffected by postcuring
      temperature and time. This phenomenon, which is related to high gas pressure in
      the bubbles, contradicts that indicated by the time-temperature-transformation
      cure diagram. High bubble pressure promotes the movement of molecular chains
      under heating at low temperature and simultaneously suppresses the etherification
      cross-linking reaction during post-curing.

PMID- 29205535
TI  - Fine-Tuning the Energy Levels of a Nonfullerene Small-Molecule Acceptor to
      Achieve a High Short-Circuit Current and a Power Conversion Efficiency over 12%
      in Organic Solar Cells.
AB  - Organic solar cell optimization requires careful balancing of current-voltage
      output of the materials system. Here, such optimization using ultrafast
      spectroscopy as a tool to optimize the material bandgap without altering
      ultrafast photophysics is reported. A new acceptor-donor-acceptor (A-D-A)-type
      small-molecule acceptor NCBDT is designed by modification of the D and A units of
      NFBDT. Compared to NFBDT, NCBDT exhibits upshifted highest occupied molecular
      orbital (HOMO) energy level mainly due to the additional octyl on the D unit and
      downshifted lowest unoccupied molecular orbital (LUMO) energy level due to the
      fluorination of A units. NCBDT has a low optical bandgap of 1.45 eV which extends
      the absorption range toward near-IR region, down to ~860 nm. However, the 60 meV
      lowered LUMO level of NCBDT hardly changes the Voc level, and the elevation of
      the NCBDT HOMO does not have a substantial influence on the photophysics of the
      materials. Thus, for both NCBDT- and NFBDT-based systems, an unusually slow (~400
      ps) but ultimately efficient charge generation mediated by interfacial charge
      pair states is observed, followed by effective charge extraction. As a result,
      the PBDB-T:NCBDT devices demonstrate an impressive power conversion efficiency
      over 12%-among the best for solution-processed organic solar cells.

PMID- 29205536
TI  - Energy-Structure-Function Maps: Cartography for Materials Discovery.
AB  - Some of the most successful approaches to structural design in materials
      chemistry have exploited strong directional bonds, whose geometric reliability
      lends predictability to solid-state assembly. For example, metal-organic
      frameworks are an important design platform in materials chemistry. By contrast,
      the structure of molecular crystals is defined by a balance of weaker
      intermolecular forces, and small changes to the molecular building blocks can
      lead to large changes in crystal packing. Hence, empirical rules are inherently
      less reliable for engineering the structures of molecular solids. Energy
      structure-function (ESF) maps are a new approach for the discovery of functional
      organic crystals. These maps fuse crystal-structure prediction with the
      computation of physical properties to allow researchers to choose the most
      promising molecule for a given application, prior to its synthesis. ESF maps were
      used recently to discover a highly porous molecular crystal that has a high
      methane deliverable capacity and the lowest density molecular crystal reported to
      date (r = 0.41 g cm-3 , SABET = 3425 m2 g-1 ). Progress in this field is
      reviewed, with emphasis on the future opportunities and challenges for a design
      strategy based on computed ESF maps.

PMID- 29205538
TI  - Corrigendum.

PMID- 29205537
TI  - A 3D Self-Shaping Strategy for Nanoresolution Multicomponent Architectures.
AB  - 3D printing or fabrication pursues the essential surface behavior manipulation of
      droplets or a liquid for rapidly and precisely constructing 3D multimaterial
      architectures. Further development of 3D fabrication desires a self-shaping
      strategy that can heterogeneously integrate functional materials with disparate
      electrical or optical properties. Here, a 3D liquid self-shaping strategy is
      reported for rapidly patterning materials over a series of compositions and
      accurately achieving micro- and nanoscale structures. The predesigned template
      selectively pins the droplet, and the surface energy minimization drives the self
      shaping processing. The as-prepared 3D circuits assembled by silver nanoparticles
      carry a current of 208-448 uA at 0.01 V impressed voltage, while the 3D
      architectures achieved by two different quantum dots show noninterfering optical
      properties with feature resolution below 3 um. This strategy can facilely
      fabricate micro-nanogeometric patterns without a modeling program, which will be
      of great significance for the development of 3D functional devices.

PMID- 29205539
TI  - Liver-first versus lung-first: a new dilemma in combined organ transplantation.

PMID- 29205540
TI  - Structuring of Functional Spider Silk Wires, Coatings, and Sheets by Self
      Assembly on Superhydrophobic Pillar Surfaces.
AB  - Spider silk has recently become a material of high interest for a large number of
      biomedical applications. Previous work on structuring of silk has resulted in
      particles (0D), fibers (1D), films (2D), and foams, gels, capsules, or
      microspheres (3D). However, the manufacturing process of these structures is
      complex and involves posttreatment of chemicals unsuitable for biological
      applications. In this work, the self-assembly of recombinant spider silk on
      micropatterned superhydrophobic surfaces is studied. For the first time,
      structuring of recombinant spider silk is achieved using superhydrophobic
      surfaces under conditions that retain the bioactivity of the functionalized silk.
      By tuning the superhydrophobic surface geometry and the silk solution handling
      parameters, this approach allows controlled generation of silk coatings,
      nanowires, and sheets. The underlying mechanisms and governing parameters are
      discussed. It is believed that the results of this work pave the way for
      fabrication of silk formations for applications including vehicles for drug
      delivery, optical sensing, antimicrobial coatings, and cell culture scaffolds.

PMID- 29205541
TI  - Highly Stretchable and Reliable, Transparent and Conductive Entangled Graphene
      Mesh Networks.
AB  - A highly stretchable and reliable, transparent and conductive entangled graphene
      mesh network (EGMN) exhibits an interconnected percolation network, as usually
      shown in 1D nanowires, but with the electrical, mechanical, and thermal
      properties of 2D graphene. The unique combination of the 2D material properties
      and the network structure of wrinkled, waved, and crumpled graphene enables the
      EGMN to demonstrate excellent electrical reliability, mechanical durability, and
      thermal stability, even under harsh environmental and external conditions such as
      very high temperature, humidity, bending, and stretching. Specifically, after 100
      000 cycles of bending with radius of 2 mm, the EGMN maintains its resistance
      similar to its initial value. The EGMN shows a steady monotonic response in
      resistance to strain cycles of 50 000 times with nearly constant gauge factors of
      0.76, 1.67, and 2.55 at 10%, 40%, and 70% strains, respectively. Moreover, the
      EGMN shows very little change in resistance with the temperature increasing up to
      1000  degrees C, by in situ thermal analysis with transmission electron
      microscopy and also by long-term stability testing at 70  degrees C and 70%
      relative humidity for 30 d. These results demonstrate that this novel entangled
      graphene mesh network can significantly broaden the application areas for various
      types of wearable and stretchable devices.

PMID- 29205542
TI  - Thermally Induced Bending of ReS2 Nanowalls.
AB  - Among the variety of stimuli-responsive materials, temperature-responsive
      materials (TRMs) can adapt to the surrounding environment in the presence of a
      thermal stimulus, and they have attracted considerable attention in sensors,
      actuators, and surface engineering. However, polymers, as the most representative
      TRMs, are far from ideal with respect to long-term reliability and durability.
      Here, for the first time, an inorganic material, ReS2 , is analyzed, which
      possesses an unexpected temperature-responsive behavior that is triggered by
      stable and reversible thermally induced bending (TIB). Due to thermal
      fluctuations in the ReS2 layers, intrinsic ripples tend to aggravate rapidly with
      rising temperature. Then, the weak interlayer interaction of ReS2 is further
      weakened, thus resulting in interlayer sliding. Due to a decrease in bending
      rigidity with increasing temperature, out-of-plane bending spontaneously occurs
      in the ReS2 layers. Interestingly, this TIB of ReS2 can recover to its initial
      configuration when the temperature drops, which is further confirmed by the
      reversible wetting measurement. Above all, the TIB behavior of ReS2 exhibits
      great potential in smart applications, such as smart windows and microfluidic
      devices, and fills the significant gaps of inorganic TRMs.

PMID- 29205543
TI  - Deep insemination with sex-sorted Cashmere goat sperm processed in the presence
      of antioxidants.
AB  - Flow cytometrically sex-sorted sperm have been widely used for improving
      reproductive management in the dairy industry. However, the industrial
      application of this technology in other domestic species is largely limited by
      the lower fertility after insemination. The aim of this study was to investigate
      effects of antioxidant supplementation during the sex-sorting and freezing
      process on the quality and functions of sorted sperm from Liaoning Cashmere
      goats. We tested the effects of antioxidant supplementation during sex-sorting
      and freezing process, including ascorbic acid-2-glucoside AA-2G, glutathione,
      melatonin and vitamin C (VC), on the quality and functions of sex-sorted fresh
      and frozen-thawed sperm. Based on these experiments, we performed deep
      insemination with sex-sorted sperm using our improved strategy, in comparison to
      unsorted sperm. In Experiment 1, compared with control group and other
      antioxidants, AA-2G supplementation significantly alleviated the degradation of
      motility and viability of fresh sperm after sorting and showed the highest
      percentage of sperm with normal morphology. In addition, AA-2G supplementation
      showed an evident protection against the sorting process-induced membrane and
      acrosome damage. In Experiment 2, AA-2G supplementation was most effective in
      protecting motility, while melatonin supplementation appears to facilitate the
      degradation of quality of frozen-thawed sex-sorted sperm. In Experiment 3, we
      performed deep insemination with sperm that were sorted and frozen in the
      presence of AA-2G and obtained a satisfying pregnancy rate comparable to that
      from unsorted sperm. The results showed that AA-2G supplementation efficiently
      protects quality and function of both fresh and frozen-thawed sex-sorted sperm of
      Cashmere goats, thus obtaining a satisfying pregnancy outcome.

PMID- 29205544
TI  - Rapid Syndiospecific (Co)Polymerization of Fluorostyrene with High Monomer
      Conversion.
AB  - Fluoromonomers are difficult to polymerize through a coordination mechanism owing
      to the strong chelation between fluorine and catalysts and the electron-deficient
      double-bond. We report herein the unprecedented polymerization of para
      fluorostyrene (pFS) with excellent activity (1.12*107  g molLn-1 h-1 ),
      distinguished syndioselectivity (rrrr >99 %) and high conversion (98.4 %) using
      rare-earth-metal catalysts bearing a pyridyl methylene fluorenyl ligand. DFT
      calculations reveal polar fluorine loses overwhelming coordination priority to
      the active central metal ion due to the sterically bulky and electron-donating
      CGC-ligand, thus its power of poisoning the active species is dramatically
      weakened. Based on this, copolymerization of pFS and styrene (St) has been
      successfully achieved with high activity and controllable pFS insertion.
      Conversely, the unlinked half-sandwich rare-earth-metal system shows relatively
      lower activity, because both the transition-states and intermediates incorporate
      a MU1 -F chelated pFS.

PMID- 29205545
TI  - The use of services due to problems related to mental health and substance abuse
      problems in Finland from 2012 to 2015.
AB  - INTRODUCTION: Improving primary care services for mental health and substance
      abuse problems was one of the major goals of the Finnish national plan for mental
      health and substance abuse work. METHODS: The study data are drawn from the
      Regional Health and Well-being Study samples. Participants reported their health
      service use. RESULTS: Women and young adults used more mental health services
      than did men and older citizens. However, a significant proportion of those with
      mental health problems had not used any health services. CONCLUSIONS: More
      attention should be paid on reducing the stigma associated to mental health and
      substance abuse problems both within the health care system and the society.

PMID- 29205546
TI  - Wood-Based Nanotechnologies toward Sustainability.
AB  - With over 30% global land coverage, the forest is one of nature's most generous
      gifts to human beings, providing shelters and materials for all living beings.
      Apart from being sustainable, renewable, and biodegradable, wood and its
      derivative materials are also extremely fascinating from a materials aspect, with
      numerous advantages including porous and hierarchical structure, excellent
      mechanical performance, and versatile chemistry. Here, strategies for designing
      novel wood-based materials via advanced nanotechnologies are summarized,
      including both the controllable bottom-up assembly from the highly crystalline
      nanocellulose building block and the more efficient top-down approaches directly
      from wood. Beyond material design, recent advances regarding the sustainable
      applications of these novel wood-based materials are also presented, focusing on
      areas that are traditionally dominated by man-made nonrenewable materials such as
      plastic, glass, and metals, as well as more advanced applications in the areas of
      energy storage, wastewater treatment and solar-steam-assisted desalination. With
      all recent progress pertaining to materials' design and sustainable applications
      presented, a vision for the future engineering of wood-based materials to promote
      continuous and healthy progress toward true sustainability is outlined.

PMID- 29205547
TI  - Halogenated Alkyltetrazoles for the Rational Design of FeII Spin-Crossover
      Materials: Fine-Tuning of the Ligand Size.
AB  - 1-(3-Halopropyl)-1H-tetrazoles and their corresponding FeII spin-crossover
      complexes have been investigated in a combined experimental and theoretical
      study. Halogen substitution was found to positively influence the spin
      transition, shifting the transition temperature about 70 K towards room
      temperature. Halogens located at the omega position were found to be too far away
      from the coordinating tetrazole moiety to have an electronic impact on the spin
      transition. The subtle variation of the steric demand of the ligand in a highly
      comparable series was found to have a comparatively large impact on the spin
      transition behavior, which highlights the sensitivity of the effect to subtle
      structural changes.

PMID- 29205548
TI  - Selective Transformation of Well-Defined Alkenyllithiums to Alkenylmagnesiums via
      Transmetalation.
AB  - A series of butadienyl organomagnesium complexes, including 1-Li-4-(MgR)
      butadienes, 1,4-bis(MgR)-butadienes, and 1-Mg-4-(MgR)-butadiene were synthesized
      starting with 1,4-dilithio butadienes via the transmetalation reaction between
      alkenyllithium bond and alkenylmagnesium bond. Single-crystal X-ray structural
      analysis of these butadienyl organomagnesiates revealed unique bonding modes.
      Study on their structural transformation demonstrated that 1-Li-4-(MgR)-butadiene
      is the key intermediate in the reaction process leading to the formation of 1,4
      bis(MgR)-butadiene and 1-Mg-4-(MgR)-butadiene.

PMID- 29205549
TI  - Identification and characterization of antibodies elicited by human cystatin C
      fragment.
AB  - Amyloid formation is associated with a number of neurodegenerative diseases that
      affect the independence and quality of life of aging populations. One of rather
      atypical, occurring at a young age amyloidosis is hereditary cystatin C amyloid
      angiopathy (HCCAA) related to aggregation of L68Q variant of human cystatin C
      (hCC). Human cystatin C plays a very important role in many aspects of human
      health; however, its amyloidogenic properties manifested in HCCAA present a real,
      lethal threat to some populations and any work on factors that can affect
      possible influencing hCC aggregation is not to overestimate. It was proved that
      interaction of hCC with monoclonal antibodies suppresses significantly hCC
      dimerization process. Therefore, immunotherapy seems to be the right approach
      toward possible HCCAA treatment. In this work, the hCC fragment encompassing
      residue 60-70 (in 2 variants: linear peptide and multiple antigenic peptide) was
      used as an immunogen in rabbit immunization. As a result, specific anti-hCC
      antibodies were found in both rabbit sera. Surprisingly, rabbit antibodies were
      obtained after immunization with only a short peptide. The obtained antibodies
      were characterized, and their influence on the aggregation propensity of the hCC
      molecules was evaluated. The antibodies turned out not to have any significant
      influence on the cystatin C dimerization process. Nevertheless, we hope that
      antibodies elicited in rabbits by other hCC fragments could lead to elaboration
      of effective treatment against HCCAA.

PMID- 29205550
TI  - Co-Structure-Directing Effect in Ionothermal Synthesis of Extra-Large-Pore
      Aluminophosphate Zeotype with -CLO Topology.
AB  - The ionothermal synthesis of extra-large-pore aluminophosphate zeotype with -CLO
      topological structure, DNL-1, was studied by using 1,6-hexanediamine and several
      quaternary ammonium compounds with different types of cations and anions as co
      structure-directing agents (co-SDAs). The phase selectivity and crystallization
      process were investigated, and results showed that the crystallization of the 
      CLO and LTA structures correlated with the alkalinity and concentration, rather
      than with the structure of the co-SDA. By combining solid/solution 13 C NMR
      spectroscopy and other characterizations on DNL-1 obtained with different co
      SDAs, it was demonstrated that the ionic-liquid cation was unalterably occluded
      in the structure, whereas occlusion of the co-SDA cation was not imperative. A
      plausible crystallization pathway was accordingly deduced, in which alkaline co
      SDA, which acted as an acidity regulator in the ionothermal system, could
      facilitate the formation of the double-four-ring (d4r) unit (Al4 P4 O20 ), and
      influence their subsequent assembly mode around ionic-liquid cations, and thus,
      direct the crystallization of -CLO and LTA structures at different concentrations
      of co-SDA.

PMID- 29205551
TI  - Regulatory genes coordinating antibiotic-induced changes in promoter activity and
      early transcriptional termination of the mycobacterial intrinsic resistance gene
      whiB7.
AB  - Diseases caused by various Mycobacterium sp., especially Mycobacterium
      tuberculosis, are a major burden on global health care. Due to high intrinsic
      antibiotic resistance, treatment options are severely limited. In mycobacteria,
      WhiB7 coordinates intrinsic resistance to a broad range of antibiotics. While
      WhiB7 has been established as an auto-regulatory transcriptional activator, the
      signals and genes needed to induce its expression are poorly understood. Using
      Mycobacterium smegmatis as a model, we coupled transposon mutagenesis and next
      generation sequencing with WhiB7-specific antibiotic selection to identify genes
      that contribute to WhiB7 regulation and function. We showed that whiB7 expression
      was regulated by two coordinated processes: early termination of the whiB7
      transcript and increased whiB7 promoter activity. Early termination was
      irreversibly maintained by constitutive expression of a putative aspartate
      aminotransferase gene, MSMEG_4060. A pair of hypothetical genes, MSMEG_3637 and
      MSMEG_3638, were identified as important contributors to whiB7 promoter induction
      on antibiotic challenge. Expansion of our understanding of the WhiB7-resistance
      pathway may lead to identification of inhibitors that allow the use of previously
      ineffective antibiotics to treat mycobacterial diseases.

PMID- 29205552
TI  - The role of the CroR response regulator in resistance of Enterococcus faecalis to
      D-cycloserine is defined using an inducible receiver domain.
AB  - Enterococcus faecalis is an opportunistic multidrug-resistant human pathogen
      causing severe nosocomial infections. Previous investigations revealed that the
      CroRS two-component regulatory pathway likely displays a pleiotropic role in E.
      faecalis, involved in virulence, macrophage survival, oxidative stress response
      as well as antibiotic resistance. Therefore, CroRS represents an attractive
      potential new target for antibiotherapy. In this report, we further explored
      CroRS cellular functions by characterizing the CroR regulon: the 'domain
      swapping' method was applied and a CroR chimera protein was generated by fusing
      the receiver domain from NisR to the output domain from CroR. After demonstrating
      that the chimera CroR complements a croR gene deletion in E. faecalis (stress
      response, virulence), we conducted a global gene expression analysis using RNA
      Seq and identified 50 potential CroR targets involved in multiple cellular
      functions such as cell envelope homeostasis, substrate transport, cell
      metabolism, gene expression regulation, stress response, virulence and antibiotic
      resistance. For validation, CroR direct binding to several candidate targets was
      demonstrated by EMSA. Further, this work identified alr, the gene encoding the
      alanine racemase enzyme involved in E. faecalis resistance to D-cycloserine, a
      promising antimicrobial drug to treat enterococcal infections, as a member of the
      CroR regulon.

PMID- 29205553
TI  - Vitronectin (Vn) glycosylation patterned by lectin affinity assays-A potent
      glycoproteomic tool to discriminate plasma Vn from cancer ascites Vn.
AB  - Changes in glycosylation have been associated with human cancer, but their
      complexity poses an analytical challenge. Ovarian cancer is a major cause of
      death in women because of an often late diagnosis. At least one-third of patients
      presents ascites fluid at diagnosis, and almost all have ascites at recurrence.
      Vitronectin (Vn) is a multifunctional glycoprotein that is suggested to be
      implicated in ovarian cancer metastasis and is found within ascites. The present
      study evaluated the potential of using lectin affinity for characterizing the
      glycosylation pattern of Vn. Human Vn was purified from 1 sample of ovarian
      cancer ascites or a pool of plasma samples. Consistent findings were observed
      with both dot blot and lectin array assays. Based on a panel of 40 lectins, the
      lectin array revealed discriminant patterns of lectin binding to Vn glycans.
      Interestingly, almost all the highlighted interactions were found to be higher
      with Vn from ascites relative to the plasma counterpart. Also, the lectin array
      was able to discriminate profiles of lectin interactions (ConA, SNA-I, PHA-E, PHA
      L) between Vn samples that were not evident using dot blot, indicating its high
      sensitivity. The model of ConA binding during thermal unfolding of Vn confirmed
      the higher accessibility of mannosylated glycans in Vn from ascites as monitored
      by turbidimetry. Thus, this study demonstrated the usefulness of lectins and the
      lectin array as a glycoproteomic tool for high throughput and sensitive analysis
      of glycosylation patterns. Our data provide novel insights concerning Vn
      glycosylation patterns in clinical specimens, paving the way for further
      investigations regarding their functional impact and clinical interest.

PMID- 29205555
TI  - On the Lewis Acidity of the Oxoiron(IV) Unit in a Tetramethylcyclam Complex.
AB  - The correlation between oxidation state and Lewis acidity is well established for
      hexaquairon complexes in the +II and +III oxidation state, in which the higher
      oxidation state leads to a lower pKa for the bound H2 O ligand. This article
      addresses the Lewis acidity of the oxoiron(IV) complex [FeIV (O)(TMC)(OH2 )]2+ (1
      OH2 ; TMC=1,4,8,11-tetramethylcyclam) by determining the pKa of the H2 O ligand.
      We establish that 1-OH2 has a pKa of 6.9+/-0.5, a value that falls in between
      those found for [FeIII (OH2 )6 ]3+ and [FeII (OH2 )6 ]2+ . This intermediate
      value can be readily rationalized by the presence of the highly basic oxide
      ligand that mitigates the Lewis acidity of the iron(IV) center. Although the oxo
      ligand occupies only one position in 1-OH2 , anti to all four methyl groups that
      protrude from the same face of the nonplanar TMC ligand, its conjugate base 1-OH
      exists as a mixture of syn and anti tautomers, which are related by proton
      transfer between the oxo and the hydroxo ligands.

PMID- 29205556
TI  - Rational Design of Organically Functionalized Polyoxopalladates and Their
      Supramolecular Properties.
AB  - The SrII -centered 12-palladate(II) open-cube {SrPd12 (OAc)3 } has been
      systematically evolved by substitution of the three acetate ligands by a library
      of saturated carboxylic acids with increasing chain lengths leading to four novel
      polyoxopalladates(II) with the formula [SrPd12 O6 (OH)3 (PhAsO3 )6 (L)3 ]4-
      (SrPd12 L3 , L=Cn H2n+1 COO, n=2 to 5). These first examples of surfactant-type
      polyoxopalladates with a hydrophilic metal-oxo unit and three hydrophobic alkyl
      chains were characterized in the solid state (single-crystal XRD, FTIR, TGA), in
      solution (1 H, 13 C NMR spectroscopy), and in the gas phase (ESI-MS). The two
      polyanions SrPd12 L3 with chain lengths of 5 and 6 are the first examples of
      polyoxopalladates that are soluble and stable in organic media. The Na salts of
      the amphiphilic polyoxopalladates SrPd12 L3 were shown to self-assemble into
      "blackberry"-type spherical supramolecular structures in dilute solutions, of
      which an unusual "volcano"-shaped trend of assembly size versus solvent polarity
      is chiefly influenced by directional hydrogen bonding interactions.

PMID- 29205554
TI  - VapA of Rhodococcus equi binds phosphatidic acid.
AB  - Rhodococcus equi is a multihost, facultative intracellular bacterial pathogen
      that primarily causes pneumonia in foals less than six months in age and
      immunocompromised people. Previous studies determined that the major virulence
      determinant of R. equi is the surface bound virulence associated protein A
      (VapA). The presence of VapA inhibits the maturation of R. equi-containing
      phagosomes and promotes intracellular bacterial survival, as determined by the
      inability of vapA deletion mutants to replicate in host macrophages. While the
      mechanism of action of VapA remains elusive, we show that soluble recombinant
      VapA32-189 both rescues the intramacrophage replication defect of a wild type R.
      equi strain lacking the vapA gene and enhances the persistence of nonpathogenic
      Escherichia coli in macrophages. During macrophage infection, VapA was observed
      at both the bacterial surface and at the membrane of the host-derived R. equi
      containing vacuole, thus providing an opportunity for VapA to interact with host
      constituents and promote alterations in phagolysosomal function. In support of
      the observed host membrane binding activity of VapA, we also found that rVapA32
      189 interacted specifically with liposomes containing phosphatidic acid in vitro.
      Collectively, these data demonstrate a lipid binding property of VapA, which may
      be required for its function during intracellular infection.

PMID- 29205557
TI  - Efficient Reduction of CO2 to CO Using Cobalt-Cobalt Oxide Core-Shell Catalysts.
AB  - The route of converting CO2 to CO by reverse water-gas shift (RWGS) reaction is
      of particular interest due to the direct use of CO as feedstock in many
      significant industrial processes. Here, an engineered cobalt-cobalt oxide core
      shell catalyst (Co@CoO) with nanochains structure has been made for the efficient
      reduction of CO2 to useful CO. Owing to the excellent performance for H2
      activation of metal nanoparticles and the enhanced absorption and activation for
      CO2 molecule of defective metal oxides, the unique synergistic effect of metallic
      Co and encapsulating coordinatively unsaturated CoO species shows high
      performance for clean generation of CO under moderate and practical conditions.
      Furthermore, with N-dopant into the defective CoO shell, the Co@CoO-N achieves
      the highest conversion of 19.2 % and an exceptional CO evolution rate of 96 mL
      min-1  gcat-1 at 523 K with a gas hourly space velocity (GHSV) of 42,000 mL gcat
      1  h-1 , which is comparable with the previously reported materials under
      identical conditions.

PMID- 29205558
TI  - Superconducting Hydrogen Sulfide.
AB  - The recent discovery of superconductivity above 200 K in hydrogen sulfide under
      high pressure marks a milestone in superconductor research. Not only does its
      critical temperature Tc exceed the previous record in cuprates by more than 50 K,
      the superconductivity in hydrogen sulfide also exhibits convincing evidence that
      it is of conventional phonon-mediated type. Moreover, this is the first time that
      a previously unknown high-Tc superconductor is predicted by theory and afterwards
      verified by experiment. In this Minireview, we survey the progress made in the
      last three years in understanding this novel material, and discuss unsolved
      problems and possible developments to encourage future investigations.

PMID- 29205559
TI  - Bandgap Optimization of Perovskite Semiconductors for Photovoltaic Applications.
AB  - The bandgap is the most important physical property that determines the potential
      of semiconductors for photovoltaic (PV) applications. This Minireview discusses
      the parameters affecting the bandgap of perovskite semiconductors that are being
      widely studied for PV applications, and the recent progress in the optimization
      of the bandgaps of these materials. Perspectives are also provided for guiding
      future research in this area.

PMID- 29205560
TI  - Targeting cancer stem cells and signaling pathways by resveratrol and
      pterostilbene.
AB  - In past decades, increasing evidence regarding cancer stem cells (CSCs) may
      account for carcinogenesis, tumor drug-resistant, and metastasis. CSCs are even
      considered as the root causes of tumor recurrence and metastases. Targeting CSCs
      may provide a new clue to cure cancer. Epidemiological and clinical studies have
      suggested that intake of dietary natural products may bring health benefits
      including lowering risk of cancer incidence. In this review, we have particularly
      focused on targeting signaling pathways of CSCs by natural resveratrol and its
      dimethylated derivative pterostilbene. (c) 2017 BioFactors, 44(1):61-68, 2018.

PMID- 29205561
TI  - Tracing the source of methomyl using stable isotope analysis.
AB  - RATIONALE: Pesticide self-poisoning is a major method of suicide in many
      agricultural communities worldwide. In addition, there are a number of known
      crime cases related to people being harmed by insecticides. Methomyl, a
      prohibited insecticide in the Republic of Korea, has high toxicity and is
      frequently used for self-poisoning. In this study, we investigated the source of
      origin of methamyl in a fatal poisoning case using stable isotope ratio analysis.
      METHODS: Two bottles of Soju from a crime scene were seized and nine different
      brands of methomyl products were collected from the neighborhood for analysis. In
      addition, the gastric contents and energy drink from the person who had committed
      suicide were analyzed. Isotope analysis using GC/Isolink/IRMS was conducted to
      determine the source of the methomyl by comparing their carbon and nitrogen
      isotope ratios. Linear discriminant analysis was utilized to verify the results.
      RESULTS: Isotope ratio analysis showed that the isotope ratio ranges of methomyl
      found in the Soju, the gastric contents of the suicide victim, and the energy
      drink bottle were similar to those of a seized methomyl product, Samgong methomyl
      2011 (SG11). Thus, it was assumed that SG11 was used in this fatal poisoning
      case. CONCLUSIONS: This study demonstrates the potential of stable isotope ratio
      analysis for the determination of insecticide origin in fatal poisoning cases.

PMID- 29205562
TI  - Ammonothermal Synthesis and Optical Properties of Ternary Nitride Semiconductors
      Mg-IV-N2 , Mn-IV-N2 and Li-IV2 -N3 (IV=Si, Ge).
AB  - Grimm-Sommerfeld analogous nitrides MgSiN2 , MgGeN2 , MnSiN2 , MnGeN2 , LiSi2 N3
      and LiGe2 N3 (generally classified as II-IV-N2 and I-IV2 -N3 ) are promising
      semiconductor materials with great potential for application in (opto)electronics
      or photovoltaics. A new synthetic approach for these nitride materials was
      developed using supercritical ammonia as both solvent and nitride-forming agent.
      Syntheses were conducted in custom-built high-pressure autoclaves with alkali
      metal amides LiNH2 , NaNH2 or KNH2 as ammonobasic mineralizers, which accomplish
      an adequate solubility of the starting materials and promote the formation of
      reactive intermediate species. The reactions were performed at temperatures
      between 870 and 1070 K and pressures up to 230 MPa. All studied compounds
      crystallize in wurtzite-derived superstructures with orthorhombic space groups
      Pna21 (II-IV-N2 ) and Cmc21 (I-IV2 -N3 ), respectively, which was confirmed by
      powder X-ray diffraction. Optical bandgaps were estimated from diffuse
      reflectance spectra using the Kubelka-Munk function (MgSiN2 : 4.8 eV, MgGeN2 :
      3.2 eV, MnSiN2 : 3.5 eV, MnGeN2 : 2.5 eV, LiSi2 N3 : 4.4 eV, LiGe2 N3 : 3.9 eV).
      Complementary DFT calculations were carried out to gain insight into the
      electronic band structures of these materials and to corroborate the optical
      measurements.

PMID- 29205563
TI  - Tetraphenylethylene Foldamers with Double Hairpin-Turn Linkers, TNT-Binding Mode
      and Detection of Highly Diluted TNT Vapor.
AB  - Tetraphenylethylene (TPE) foldamers with double hairpin-turn linkers showing an
      aggregation-induced emission (AIE) effect have been synthesized for the first
      time. A crystal structure of a foldamer-TNT complex has been obtained, enabling
      unprecedented direct observation of the interactions between TNT molecules and
      the chromophores of the foldamer. Instead of pi-pi stacking interactions, which
      have often been considered to be the key mechanism in the binding of TNT by
      chromophoric receptors, strong n-pi interactions between the nitro groups of TNT
      and the aromatic rings of the foldamer have been found. Exceptionally, by
      addition of 1 % NaF to a suspension of the foldamer in H2 O/THF (95:5), the
      fluorescence quenching efficiency by TNT vapor significantly increased from about
      20 % to more than 90 %. Even after diluting TNT-saturated air at 25  degrees C by
      a factor of 2*104 , an obvious quenching response was observed, indicating that
      ultratrace TNT vapor (down to 3.4 fg per mL of air) could be detected.

PMID- 29205564
TI  - Efficient Buchwald-Hartwig-Migita Cross-Coupling for DNA Thioglycoconjugation.
AB  - An efficient method for the thioglycoconjugation of iodinated oligonucleotides by
      Buchwald-Hartwig-Migita cross-coupling under mild conditions is reported. The
      method enables divergent synthesis of many different functionalized
      thioglycosylated ODNs in good yields, without affecting the integrity of the
      other A, C, and G nucleobases.

PMID- 29205565
TI  - Binding Profiles of Self-Assembled Supramolecular Cages from ESI-MS Based
      Methodology.
AB  - Confined molecular environments have peculiar characteristics that make their
      properties unique in the field of biological and chemical sciences. In recent
      years, advances in supramolecular capsule and cage synthesis have presented the
      possibility to interpret the principles behind their self-assembly and functions,
      which has led to new molecular systems that display outstanding properties in
      molecular recognition and catalysis. Herein, we report a rapid method based on
      ESI-MS to determine the binding profiles for linear saturated dicarboxylic acids
      in a series of different cages. The cages were obtained by self-assembly of
      modified tris(pyridylmethyl)amine (TPMA) complexes and diamines chosen to explore
      variations in their size and flexibility. This methodology has provided
      information on how small changes in the structures of the host and guest can
      contribute to recognition events. Moreover, it was possible to study molecular
      systems that contain paramagnetic metals, which are not suitable for classical
      binding-constant determination by 1 H NMR spectroscopy.

PMID- 29205566
TI  - Transglutaminase type 2 plays a key role in the pathogenesis of Mycobacterium
      tuberculosis infection.
AB  - BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of
      tuberculosis (TB), is capable of interfering with the phagosome maturation
      pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to
      ensure survival and replication in macrophages. Thus, it has been proposed that
      the modulation of autophagy may represent a therapeutic approach to reduce MTB
      viability by enhancing its clearance. OBJECTIVE: The aim of this study was to
      investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis
      of MTB. RESULTS: We have shown that either genetic or pharmacological inhibition
      of TG2 leads to a marked reduction in MTB replicative capacity. Infection of TG2
      knockout mice demonstrated that TG2 is required for MTB intracellular survival in
      macrophages and host tissues. The same inhibitory effect can be reproduced in
      vitro using Z-DON, a specific inhibitor of the transamidating activity of TG2.
      Massive cell death observed in macrophages that properly express TG2 is hampered
      by the absence of the enzyme and can be largely reduced by the treatment of wild
      type macrophages with the TG2 inhibitor. Our data suggest that reduced MTB
      replication in cells lacking TG2 is due to the impairment of LC3/autophagy
      homeostasis. Finally, we have shown that treatment of MTB-infected murine and
      human primary macrophages with cystamine, a TG2 inhibitor already tested in
      clinical studies, causes a reduction in intracellular colony-forming units in
      human macrophages similar to that achieved by the anti-TB drug capreomycin.
      CONCLUSION: These results suggest that inhibition of TG2 activity is a potential
      novel approach for the treatment of TB.

PMID- 29205567
TI  - Analytical Understanding of the Materials Design with Well-Described Shrinkages
      on Multiscale.
AB  - Shrinkages derived from condensation of frameworks are one of the significant
      steps for fabricating demanded materials having unique morphologies and
      properties. Enormous efforts have been dedicated to understanding their
      mechanisms that are quite useful for the materials design. In this context,
      diversified measuring and observing tools have been facilitated to evaluate
      structural contractions and corresponding driving forces. All of the
      investigations are crucial to encourage the utilization of such shrinkages for
      the precise design of nanomaterials. In this review, we summarize significant
      works how to analyze shrinkages in multiscale during the synthesis of materials,
      which will be useful as a follow-up review to our latest contribution. Well
      defined porous materials are also selected as a good candidate for understanding
      well-described shrinkages. This review aims to provide a detailed glimpse of the
      development of analyses on shrinking behaviors in multiscale for the materials
      design. Shrinking degree and direction in multiscale, which are driven by
      condensation of frameworks, are predominant for understanding and/or predicting
      final nanostructures of materials after shrinkages.

PMID- 29205568
TI  - Johnson Solids: Anion-Templated Silver Thiolate Clusters Capped by Sulfonate.
AB  - Sulfonates were incorporated into six novel high-nuclearity silver(I) thiolate
      clusters under the guidance of anion templates varied from S2- , SO42- , alpha
      [Mo5 O18 ]6- , beta-[Mo5 O18 ]6- , [Mo2 O8 ]4- , to [Mo4 O14 (SO4 )]6- . Single
      crystal X-ray analysis revealed that SD/Ag1, SD/Ag3, SD/Ag5, and SD/Ag6 are
      discrete [S@Ag60 ], [alpha-Mo5 O18 @Ag36 ], [Mo2 O8 @Ag30 ]2 , and [Mo4 O14 (SO4
      )@Ag73 ] clusters, respectively, whereas SD/Ag2 and SD/Ag4 are one-dimensional
      (1D) chains based on the [SO4 @Ag20 ] and [beta-Mo5 O18 @Ag36 ] cluster subunits,
      respectively. Their silver skeletons are protected exteriorly by thiolates and
      sulfonates and interiorly supported by diverse anions as templates. Structurally,
      cluster SD/Ag1 is a typical core-shell structure comprised of an inner Ag12
      cuboctahedron and an outer Ag48 shell. The sulfate-templated drum-like Ag20
      cluster subunits are bridged by PhSO3- to give a 1D chain of SD/Ag2. Complex
      SD/Ag3 and SD/Ag4 are spindle-like Ag36 clusters with isomeric [Mo5 O18 ]6-
      inside, and the latter is further extended to a 1D chain through PhSO3- bridges.
      A pair of [Mo2 O8 ]4- templated gourd-like Ag30 clusters are dimerized in a head
      to-head fashion to form SD/Ag5. Complex SD/Ag6 is the largest cluster in this
      family and doubly templated by unprecedented [Mo4 O14 (SO4 )]6- anions.
      Geometrically, the silver shells of SD/Ag1-SD/Ag5 show the polyhedral features of
      Johnson solids, instead of the usual Platonic or Archimedean solids. Solution
      behaviors and luminescent properties were also investigated in detail.

PMID- 29205569
TI  - No difference in self-reported frequency of choking between infants introduced to
      solid foods using a baby-led weaning or traditional spoon-feeding approach.
AB  - BACKGROUND: Baby-led weaning (BLW) where infants self-feed family foods during
      the period that they are introduced to solid foods is growing in popularity. The
      method may promote healthier eating patterns, although concerns have been raised
      regarding its safety. The present study therefore explored choking frequency
      amongst babies who were being introduced to solid foods using a baby-led or
      traditional spoon-fed approach. METHODS: In total, 1151 mothers with an infant
      aged 4-12 months reported how they introduced solid foods to their infant
      (following a strict BLW, loose BLW or traditional weaning style) and frequency of
      spoon-feeding and puree use (percentage of mealtimes). Mothers recalled if their
      infant had ever choked and, if so, how many times and on what type of food
      (smooth puree, lumpy puree, finger food and specific food examples). RESULTS: In
      total, 13.6% of infants (n = 155) had ever choked. No significant association was
      found between weaning style and ever choking, or the frequency of spoon or puree
      use and ever choking. For infants who had ever choked, infants following a
      traditional weaning approach experience significantly more choking episodes for
      finger foods (F2,147  = 4.417, P = 0.014) and lumpy purees (F2,131  = 6.46, P =
      0.002) than infants following a strict or loose baby-led approach. CONCLUSIONS:
      Baby-led weaning was not associated with increased risk of choking and the
      highest frequency of choking on finger foods occurred in those who were given
      finger foods the least often. However, the limitations of noncausal results, a
      self-selecting sample and reliability of recall must be emphasised.

PMID- 29205570
TI  - Brain angiogenic gene expression in fetuses with congenital heart disease.
AB  - OBJECTIVE: To assess potential differences in the expression of antiangiogenic
      and angiogenic factors and of genes associated with chronic hypoxia in cerebral
      tissue of euploid fetuses with congenital heart disease (CHD) vs those without.
      METHODS: Cerebral tissue was obtained from 15 fetuses with CHD and 12 control
      fetuses that had undergone termination of pregnancy. Expression profiles of the
      antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic
      vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF),
      and of genes associated with chronic hypoxia were determined by real-time
      polymerase chain reaction in tissue from the frontal cortex and the basal ganglia
      of the fetuses. RESULTS: Expression of sFlt-1 was 48% higher in the frontal
      cortex (P = 0.0431) and 72% higher in the basal ganglia (P = 0.0369) of CHD
      fetuses compared with controls. The expression of VEGF-A was 60% higher (P =
      0.0432) and that of hypoxia-inducible factor 2-alpha was 98% higher (P = 0.0456)
      in the basal ganglia of CHD fetuses compared with controls. No significant
      differences were observed between the two groups in the expression of PlGF and
      hypoxia-inducible factor 1-alpha. CONCLUSION: An overall dysregulation of
      angiogenesis with a net balance towards an antiangiogenic environment was
      observed in the cerebral tissue of fetuses with CHD, suggesting that these
      fetuses may have an intrinsic angiogenic impairment that could contribute to
      impaired brain perfusion and abnormal neurological development later in life.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29205571
TI  - Ultrasound curricula in obstetrics and gynecology training programs.

PMID- 29205572
TI  - A Luminescent Dinuclear EuIII /TbIII Complex with LMCT Band as a Single-Molecular
      Thermosensor.
AB  - Temperature-dependent luminescence of a dinuclear EuIII /TbIII complex with a
      seven-coordinate structure is demonstrated. The dinuclear complex is composed of
      two lanthanide ions, six tetramethylheptanedionate ligands, and a bidentate
      phosphine oxide linker ligand. The dinuclear structure of the complex was
      characterized by single-crystal XRD. Intrinsic 4f-4f emission quantum yields of
      the dinuclear EuIII and TbIII complexes were 66 and 61 %, respectively. The
      luminescence color of the dinuclear EuIII /TbIII complex changed from red to
      green with increasing temperature. The thermosensing range based on the ratio of
      luminescence intensity (AEu /ATb ) was 100-450 K. The temperature-dependent
      luminescence is due to the presence of a ligand-to-metal charge-transfer state.

PMID- 29205573
TI  - Serum relaxin and cervical length for prediction of spontaneous preterm birth in
      second-trimester symptomatic women.
AB  - OBJECTIVE: To investigate whether serum relaxin level is associated with preterm
      birth in symptomatic women, either as a standalone test or in the context of a
      combined model of serum relaxin and cervical length (CL). METHODS: This was a
      case-control study of women with a singleton pregnancy who presented between 24 +
      0 and 26 + 6 weeks' gestation with threatened preterm labor and intact membranes.
      CL, full blood count, C-reactive protein level and maternal demographics were
      recorded at presentation, and blood samples were taken for relaxin measurement.
      Parameters were compared between women who delivered preterm (before 37 weeks) (n
      = 46) and those delivering at term (n = 66). Logistic regression with receiver
      operating characteristics (ROC) curve analysis was used to assess significant
      predictors for birth before 37 and before 34 weeks. RESULTS: Women delivering
      before 37 weeks had higher mean serum relaxin levels and lower mean CL than those
      delivering at term (P < 0.0001). Relaxin alone had 63% (95% CI, 49-75%)
      sensitivity for birth before 37 weeks and 61% (95% CI, 47-74%) for birth before
      34 weeks, at a 10% false-positive rate (FPR). Serum relaxin levels did not
      correlate with CL; a combined model of the two predictors had an area under the
      ROC curve of 0.895 (95%CI, 0.835-0.954) for the prediction of birth before 37
      weeks and 0.869 (95% CI, 0.802-0.937) for birth before 34 weeks (n =  44). Serum
      relaxin > 1010 pg/mL had 58% sensitivity for prediction of preterm birth in women
      with a CL > 15 mm, at a 10% FPR. CONCLUSIONS: High serum relaxin level is
      associated with an increased risk of preterm birth in second-trimester
      symptomatic women with intact membranes. A combination of serum relaxin and CL
      increases predictive accuracy for preterm birth. Copyright (c) 2017 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 29205574
TI  - Different pre-scanning instructions induce distinct psychological and resting
      brain states during functional magnetic resonance imaging.
AB  - Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to
      investigate functional brain network connectivity during rest or when the subject
      is not performing an explicit task. In the standard procedure, subjects are
      instructed to 'let your mind wander' or 'think of nothing'. While these
      instructions appear appropriate to induce a 'resting-state', they could induce
      distinct psychological and physiological states during the scan. In this study,
      we investigated whether different instructions affect mental state and functional
      connectivity (FC) (i.e. induce distinct 'resting states') during rs-fMRI
      scanning. Thirty healthy subjects were subjected to two rs-fMRI scans differing
      only in pre-scan instructions: think of nothing (TN) and mind-wandering (MW)
      conditions. Self-reports confirmed that subjects spent the majority of the
      scanning time in the appropriate mental state. Independent component analysis
      extracted 19 independent components (ICs) of interest and functional network
      connectivity analyses indicated several conditional differences in FCs among
      those ICs, especially characterised by stronger FC in the MW condition than in
      the TN condition, between default mode network and salience/visual/frontal
      network. Complementary correlation analysis indicated that some of the network
      FCs were significantly correlated with their self-reported data on how often they
      had the TN condition during the scans. The present results provide evidence that
      the pre-scan instruction has a significant influence on resting-state FC and its
      relationship with mental activities.

PMID- 29205575
TI  - Panchromatic Photosensitizers Based on Push-Pull, Unsymmetrically Substituted
      Porphyrazines.
AB  - A series of five push-pull porphyrazines of A3 B type, in which unit B is an
      isoindole 4-carboxylic acid, has been prepared. The units A have been endowed
      with thioether, amine, ether and alkyl functions, either directly attached to the
      beta-position of the pyrrolic units, or connected to the porphyrazine core
      through p-substituted phenyl groups. Attaching the electron-donor functions to
      the porphyrazine periphery produces strong perturbations in the electronic and
      redox properties of the dyes. Their HOMO and LUMO energies, estimated from the
      optical and redox data, as well as with DFT calculations, raise upon
      functionalization with amines, while the corresponding frontier orbital energetic
      levels lower upon functionalization with thioethers, p-methoxyphenyl or p-tert
      butylphenyl groups. The effective interaction of peripheral substitution with the
      macrocycle produces chromophores with panchromatic absorption between 300 and 750
      850 nm.

PMID- 29205577
TI  - Corrigendum.

PMID- 29205576
TI  - Investigation of (Me4 N)SCF3 as a Stable, Solid and Safe Reservoir for S=CF2 as a
      Surrogate for Thiophosgene.
AB  - While thiophosgene finds widespread usage on a multi-ton scale, its fluorinated
      counterpart S=CF2 is essentially unexplored in synthesis. Using experimental
      reactivity tests, ReactIR and computational techniques, we herein showcase that
      the solid (Me4 N)SCF3 functions as a safe reservoir for S=CF2 . A key feature is
      that the reactive electrophile is not simply released over time, but instead is
      liberated under activation with a protic nucleophile. The reactivity of S=CF2 is
      mild, allowing large-scale and late-stage synthetic applications without special
      reaction control. The mechanism was fully elucidated, including a rationalization
      of the role of the Me4 N cation and the origins of selectivity.

PMID- 29205578
TI  - Re: Automatic ultrasound technique to measure angle of progression during labor.
      F. Conversano, M. Peccarisi, P. Pisani, M. Di Paola, T. De Marco, R. Franchini,
      A. Greco, G. D'Ambrogio and S. Casciaro. Ultrasound Obstet Gynecol 2017; 50: 766
      775.

PMID- 29205579
TI  - Reply.

PMID- 29205580
TI  - Corrigendum.

PMID- 29205581
TI  - Alternative explanations for linking chronic hypertension to adverse pregnancy
      outcome.

PMID- 29205582
TI  - Reply.

PMID- 29205584
TI  - ISUOG Guidelines for fetal MRI: a response to 3-T fetal imaging and limited fetal
      exams.

PMID- 29205585
TI  - Re: Influence of chorionicity and gestational age at single fetal loss on risk of
      preterm birth in twin pregnancy: analysis of STORK multiple pregnancy cohort. F.
      D'Antonio, B. Thilaganathan, T. Dias and A. Khalil, on behalf of the Southwest
      Thames Obstetric Research Collaborative (STORK). Ultrasound Obstet Gynecol 2017;
      50: 723-727.

PMID- 29205587
TI  - The impact of repeat FNA in non-diagnostic and indeterminate thyroid nodules: A 5
      year single-centre experience.
AB  - INTRODUCTION: FNA is a well-established method for the preoperative diagnosis of
      thyroid nodules, but limitations still reside among non-diagnostic and
      indeterminate samples. The objective of the present study was to assess the
      impact of repeat FNA in thyroid nodules primarily classified as non-diagnostic
      and indeterminate, with the evaluation of the diagnostic resolution rate after
      the reassessment of the nodule. METHODS: We retrospectively collected all cases
      of thyroid FNA at our institution in the last 5 years that had one or more repeat
      aspirations of the same nodule, calculating the percentage of samples with change
      in the diagnostic category. Additional collected data included sex, age and
      interval between the repeat aspirations. RESULTS: One hundred and seventy-eight
      specimens from 167 patients (140 female, 27 male) with a median age of 56 years
      (range 11-90) were included in the study. Among the 86 cases primarily classified
      as non-diagnostic, 25 (29.1%) remained in the same category after the first
      reassessment and only 18 (20.9%) after the second repeat aspiration. Among the 40
      indeterminate cases, only 10 (25%) retained their status after the second
      aspiration, with no change after the third assessment. CONCLUSION: Repeat
      aspiration of non-diagnostic and indeterminate thyroid nodules had a positive
      impact in both groups, with diagnostic resolution rates of 80% and 75%,
      respectively. The present study therefore endorses the use of such strategy for
      the initial follow-up of nodules with no definite diagnosis, especially in low
      resource centres with limited access to modern molecular technologies.

PMID- 29205588
TI  - Machine learning for decoding listeners' attention from electroencephalography
      evoked by continuous speech.
AB  - Previous research has shown that it is possible to predict which speaker is
      attended in a multispeaker scene by analyzing a listener's electroencephalography
      (EEG) activity. In this study, existing linear models that learn the mapping from
      neural activity to an attended speech envelope are replaced by a non-linear
      neural network (NN). The proposed architecture takes into account the temporal
      context of the estimated envelope and is evaluated using EEG data obtained from
      20 normal-hearing listeners who focused on one speaker in a two-speaker setting.
      The network is optimized with respect to the frequency range and the temporal
      segmentation of the EEG input, as well as the cost function used to estimate the
      model parameters. To identify the salient cues involved in auditory attention, a
      relevance algorithm is applied that highlights the electrode signals most
      important for attention decoding. In contrast to linear approaches, the NN
      profits from a wider EEG frequency range (1-32 Hz) and achieves a performance
      seven times higher than the linear baseline. Relevant EEG activations following
      the speech stimulus after 170 ms at physiologically plausible locations were
      found. This was not observed when the model was trained on the unattended
      speaker. Our findings therefore indicate that non-linear NNs can provide insight
      into physiological processes by analyzing EEG activity.

PMID- 29205589
TI  - Carnosine decreased oxidation and glycation products in serum and liver of high
      fat diet and low-dose streptozotocin-induced diabetic rats.
AB  - High-fat diet (HFD) and low-dose streptozotocin (STZ)-treated rats provide useful
      animal model for type II diabetes mellitus. Oxidative stress and advanced
      glycation end products (AGEs) play a role in the development of diabetic
      complications. Carnosine (CAR) has anti-oxidant and anti-glycating properties. We
      investigated the effects of CAR on oxidation and glycation products in HFD+STZ
      rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks, and
      then a single dose of STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose
      levels above 200 mg/dl were fed with HFD until the end of the 12th week. CAR (250
      mg/kg body weight; i.p.; five times a week) was administered to the rats for the
      last four weeks. CAR significantly decreased serum triglyceride (TG) (57.7%),
      cholesterol (35.6%) levels and hepatic marker enzyme activities of HFD+STZ rats.
      It significantly reduced serum reactive oxygen species (ROS) (23.7%), AGEs
      (13.4%) and advanced oxidized protein products (AOPP) (35.9%) and hepatic TG
      (59%), ROS (26%), malondialdehyde (MDA) (11.5%), protein carbonyl (PC) (19.2%)
      and AGE (20.2%) levels. Liver steatosis and hepatocyte ballooning were also
      significantly reduced. However, CAR treatment did not alter serum glucose and
      blood glycated haemoglobin and hepatic anti-oxidant enzyme activities/mRNA
      expressions in HFD+STZ rats. Our results indicate that CAR decreased accumulation
      of oxidation and glycation products, such as MDA, AGE, AOPP and PC in the serum
      and liver and ameliorated hepatic dysfunction in HFD+STZ rats. This effect may be
      related to its anti-oxidative, anti-glycating, and anti-lipogenic potential.

PMID- 29205590
TI  - OsOFP19 modulates plant architecture by integrating the cell division pattern and
      brassinosteroid signaling.
AB  - Characterization of OVATE family proteins (OFPs) has revealed that they exert
      functions by interacting with different types of transcription factor. However,
      the molecular bases of these processes are poorly understood. Here, we report
      that OsOFP19 negatively modulates brassinosteroid (BR) response and integrates it
      with the cell division pattern to affect plant architecture, including grain
      shape, through interaction with both DWARF AND LOW-TILLERING (DLT) and Oryza
      sativa homeobox1 (OSH1). Overexpression of OsOFP19 caused a semi-dwarf stature
      with thicker leaves and stronger culms and roots, which result from an increase
      in cell layers in the sub-epidermal tissue. Further studies revealed that OsOFP19
      interacts with OSH1, and that this interaction mutually enhances the
      transcriptional activity of these proteins and leads to a transition from
      anticlinal to periclinal cell division. Furthermore, DLT interacts with both
      OsOFP19 and OSH1 and acts as an antagonist in the two interactions. Therefore,
      OsOFP19, OSH1 and DLT form a functional complex which plays a pivotal role in
      modulating BR signaling and determining the cell division pattern during plant
      growth and development.

PMID- 29205591
TI  - General One-Pot Synthesis of Transition-Metal Phosphide/Nitrogen-Doped Carbon
      Hybrid Nanosheets as Ultrastable Anodes for Sodium-Ion Batteries.
AB  - Sodium-ion batteries (SIBs) have been considered as promising energy storage
      devices in grid-level applications, owing to their largely reduced cost compared
      with that of lithium-ion batteries. However, the practical application of SIBs
      has been seriously hindered because of the lack of appropriate anode materials,
      limited by the thermodynamics perspective, which is one of the central task at
      current stage. Herein, we have developed a general one-pot strategy for the
      synthesis of transition-metal phosphide (TMP) based hybrid nanosheets composed of
      carbon-coated TMP nanoparticles anchored to the surface of nitrogen-doped carbon
      nanosheets. This facile and cost-effective method is quite universal and holds
      potential to be further extended to other metal phosphide materials.
      Significantly, the hybrid nanosheet electrode possesses excellent sodium storage
      properties as anodes for SIBs, including high specific capacity, an ultra-long
      cycle life and a remarkable rate performance. This work makes a significant
      contribution to not only the synthetic methodology of TMP-carbon two-dimensional
      hybrid nanostructures, but also the application of TMP-based anodes for high
      energy SIBs.

PMID- 29205592
TI  - Increase of prostaglandin E2 in the reversal of fetal ductal constriction after
      polyphenol restriction.
AB  - OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of
      prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and
      polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus.
      This study aimed to test the hypothesis that reversal of fetal ductal
      constriction after maternal restriction of polyphenol-rich foods, in the third
      trimester of pregnancy, is accompanied by increased plasma levels of
      prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women
      with singleton pregnancy >= 28 weeks undergoing fetal echocardiography. The
      intervention group included pregnancies with diagnosis of fetal ductal
      constriction and not exposed to NSAIDs. The control group consisted of third
      trimester normal pregnancies. Both groups answered a food frequency questionnaire
      to assess the amount of total polyphenols in their diet, underwent Doppler
      echocardiographic examination and had blood samples collected for analysis of
      plasma levels of PGE2. Intervention group participants received dietary guidance
      to restrict the intake of polyphenol-rich foods. The assessments were repeated
      after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in
      the control group and 35 with fetal ductal constriction in the intervention
      group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 )
      were similar between the two groups. Intragroup analysis showed that dietary
      guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03
      mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2
      (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 
      weeks. In addition, Doppler echocardiography showed reversal of fetal ductal
      constriction in the intervention group. No significant changes were observed in
      the control group. CONCLUSIONS: Dietary intervention for maternal restriction of
      polyphenol-rich foods in the third trimester of pregnancy is accompanied by
      increase in plasma levels of PGE2 and reversal of fetal ductal constriction.
      Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29205593
TI  - Identifying apparent local stable isotope equilibrium in a complex non
      equilibrium system.
AB  - RATIONALE: Although being out of equilibrium, biomolecules in organisms have the
      potential to approach isotope equilibrium locally because enzymatic reactions are
      intrinsically reversible. A rigorous approach that can describe isotope
      distribution among biomolecules and their apparent deviation from equilibrium
      state is lacking, however. METHODS: Applying the concept of distance matrix in
      graph theory, we propose that apparent local isotope equilibrium among a subset
      of biomolecules can be assessed using an apparent fractionation difference
      (|Deltaalpha|) matrix, in which the differences between the observed isotope
      composition (delta') and the calculated equilibrium fractionation factor
      (1000lnbeta) can be more rigorously evaluated than by using a previous approach
      for multiple biomolecules. We tested our |Deltaalpha| matrix approach by re
      analyzing published data of different amino acids (AAs) in potato and in green
      alga. RESULTS: Our re-analysis shows that biosynthesis pathways could be the
      reason for an apparently close-to-equilibrium relationship inside AA families in
      potato leaves. Different biosynthesis/degradation pathways in tubers may have led
      to the observed isotope distribution difference between potato leaves and tubers.
      The analysis of data from green algae does not support the conclusion that AAs
      are further from equilibrium in glucose-cultured green algae than in the
      autotrophic ones. CONCLUSIONS: Application of the |Deltaalpha| matrix can help us
      to locate potential reversible reactions or reaction networks in a complex system
      such as a metabolic system. The same approach can be broadly applied to all
      complex systems that have multiple components, e.g. geochemical or atmospheric
      systems of early Earth or other planets.

PMID- 29205594
TI  - Recovery of puborectalis muscle after vaginal delivery: an ultrasound study.
AB  - OBJECTIVES: To assess change in levator hiatal dimensions between pregnancy and
      different timepoints after vaginal delivery, and map recovery of the hiatus in
      order to contribute to secondary prevention of symptoms of pelvic floor
      disorders. METHODS: Twenty nulliparous women with a singleton pregnancy underwent
      ultrasound assessment of the pelvic floor at rest, on maximum pelvic floor muscle
      contraction (PFMC) and on Valsalva maneuver at 12 weeks' gestation and at 1 day
      and 1, 2, 3, 4, 6, 12, 18 and 24 weeks after vaginal delivery. Dimensions of the
      levator hiatus were measured and contractility and distensibility were
      calculated. The Wilcoxon signed rank test was used to compare each postpartum
      value with that at 12 weeks' gestation. RESULTS: Levator hiatal area at rest, on
      PFMC and on Valsalva maneuver was significantly increased at 1 day and at 1 and 2
      weeks after vaginal delivery compared with measurements at 12 weeks' gestation.
      Hiatal area at rest and on PFMC from 3 weeks postpartum onward, as well as
      contractility from 6 weeks onward, were comparable to values at 12 weeks'
      gestation, whereas, a significant difference remained on Valsalva maneuver until
      24 weeks after delivery. Moreover, distensibility was still increased at 24 weeks
      postpartum compared with measurements at 12 weeks' gestation. CONCLUSION: The
      puborectalis muscle has the ability to recover anatomically from a first vaginal
      delivery, and recovery occurs mainly during the first 3 weeks after delivery.
      Stretching of the puborectalis muscle, as reflected by distensibility, persisted
      24 weeks after the first vaginal delivery. The data provide a better
      understanding of the early 'normal' regeneration process and we hypothesize that
      the first 3 weeks postpartum is the best window in which to start secondary
      prevention. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29205595
TI  - The pseudogenes of barley.
AB  - Pseudogenes have a reputation of being 'evolutionary relics' or 'junk DNA'. While
      they are well characterized in mammals, studies in more complex plant genomes
      have so far been hampered by the absence of reference genome sequences. Barley is
      one of the economically most important cereals and has a genome size of 5.1 Gb.
      With the first high-quality genome reference assembly available for a Triticeae
      crop, we conducted a whole-genome assessment of pseudogenes on the barley genome.
      We identified, characterized and classified 89 440 gene fragments and pseudogenes
      scattered along the chromosomes, with occasional hotspots and higher densities at
      the chromosome ends. Full-length pseudogenes (11 015) have preferentially
      retained their exon-intron structure. Retrotransposition of processed mRNAs only
      plays a marginal role in their creation. However, the distribution of retroposed
      pseudogenes reflects the Rabl configuration of barley chromosomes and thus hints
      at founding mechanisms. While parent genes related to the defense-response were
      found to be under-represented in cultivated barley, we detected several defense
      related pseudogenes in wild barley accessions. The percentage of
      transcriptionally active pseudogenes is 7.2%, and these may potentially adopt new
      regulatory roles.The barley genome is rich in pseudogenes and small gene
      fragments mainly located towards chromosome tips or as tandemly repeated units.
      Our results indicate non-random duplication and pseudogenization preferences and
      improve our understanding of the dynamics of gene birth and death in large plant
      genomes and the mechanisms that lead to evolutionary innovations.

PMID- 29205596
TI  - Detection and analysis of abnormal nuclear changes in oral cytological smears by
      Papanicolaou staining.

PMID- 29205597
TI  - Selection and Screening of DNA Aptamers for Inorganic Nanomaterials.
AB  - Searching for DNA sequences that can strongly and selectively bind to inorganic
      surfaces is a long-standing topic in bionanotechnology, analytical chemistry and
      biointerface research. This can be achieved either by aptamer selection starting
      with a very large library of ~1014 random DNA sequences, or by careful screening
      of a much smaller library (usually from a few to a few hundred) with rationally
      designed sequences. Unlike typical molecular targets, inorganic surfaces often
      have quite strong DNA adsorption affinities due to polyvalent binding and even
      chemical interactions. This leads to a very high background binding making
      aptamer selection difficult. Screening, on the other hand, can be designed to
      compare relative binding affinities of different DNA sequences and could be more
      appropriate for inorganic surfaces. The resulting sequences have been used for
      DNA-directed assembly, sorting of carbon nanotubes, and DNA-controlled growth of
      inorganic nanomaterials. It was recently discovered that poly-cytosine (C) DNA
      can strongly bind to a diverse range of nanomaterials including nanocarbons
      (graphene oxide and carbon nanotubes), various metal oxides and transition-metal
      dichalcogenides. In this Concept article, we articulate the need for screening
      and potential artifacts associated with traditional aptamer selection methods for
      inorganic surfaces. Representative examples of application are discussed, and a
      few future research opportunities are proposed towards the end of this article.

PMID- 29205598
TI  - An auditory brainstem nucleus as a model system for neuronal metabolic demands.
AB  - The correlation between neuronal activity and metabolism is essential for coding,
      plasticity, neurological disorders and the interpretation of functional
      neuroimaging data. Most likely, metabolic requirements depend upon neuron type,
      and macroscopic energy demands vary with brain region. However, specific needs of
      individual neuron types are enigmatic. Therefore, we monitored metabolic activity
      in the lateral superior olive (LSO), an auditory brainstem nucleus containing
      only one neuron type. LSO neurons exhibit extreme but well-described biophysics
      with firing rates of several hundred hertz and low input resistances of a few
      megaohms. We recorded changes in NADH and flavin adenine dinucleotide (FAD)
      autofluorescence and O2 concentration in acute brainstem slices of Mongolian
      gerbils (Meriones unguiculatus) following electrical stimulation. The LSO shows
      the typical biphasic NADH/FAD response up to a physiologically relevant frequency
      of 400 Hz. In the same animal, we compared the LSO with the hippocampal CA1
      region and the cerebral cortex. The rate of NADH/FADH2 consumption and
      regeneration was slowest in LSO. However, frequency dependence was only similar
      during the consumption phase but varied during regeneration within the three
      brain regions. Changes in NADH, FAD and O2 levels and blocking metabolic
      reactions indicate a pronounced contribution of mitochondrial oxidative
      phosphorylation in the LSO which is known for the other brain regions as well.
      Lactate transport and interconversion are involved in LSO metabolism as we found
      in immunohistochemical and pharmacological experiments. Our findings show that
      the LSO represents an apt, biophysically distinct model for brain metabolism and
      that neuronal properties determine metabolic needs.

PMID- 29205599
TI  - Postnatal separation prevents the development of prenatal stress-induced anxiety
      in association with changes in oestrogen receptor and oxytocin immunoreactivity
      in female mandarin vole (Microtus mandarinus) offspring.
AB  - Oestrogen has both anxiogenic and anxiolytic effects because of variation in
      opposing action on alpha (ERalpha) and beta (ERbeta) estrogen receptors in the
      medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and
      medial amygdala (MeA). Oxytocin (OT) reverses some of the anxiogenic effects of
      oestrogen in the hypothalamic paraventricular nucleus (PVN) and supraoptic
      nucleus (SON). Because anxiety disorders are twice as common in women as in men,
      and oestrogen and OT are more important in females, we examined interactions
      between prenatal restraint stress (GS) and postnatal early short-term maternal
      separation (MS) and female mandarin vole behaviour, estrogen receptors and OT.
      The results show that adult female offspring from GS/noMS mothers showed
      increased anxiety in open-field and elevated plus-maze tests and had lower serum
      17-beta-oestradiol (E2 ) levels than female offspring from GS/MS, noGS/MS and
      noGS/noMS mothers. GS/noMS females had more immunoreactive neurons for ERalpha in
      several brain regions and less ERbeta- and OT-immunoreactive neurons in brain
      areas compared to GS/MS, noGS/MS and noGS/noMS offspring. Interestingly, noGS/MS
      and GS/MS offspring were similar to noGS/noMS offspring in that they did not
      develop anxiety as adults. We propose that MS alters the serum concentration of
      E2 and that the ERbeta/ERalpha ratio and OT level in the brain may be responsible
      for the decrease in anxiety-like behaviour in adult female offspring initially
      exposed to anxiety-inducing conditions via an adverse foetal environment.

PMID- 29205600
TI  - Circulating microRNA signature of steroid-induced osteonecrosis of the femoral
      head.
AB  - OBJECTIVES: Steroid-induced osteonecrosis of the femoral head (ONFH) is a common
      orthopaedic disease of which early detection remains clinically challenging.
      Accumulating evidences indicated that circulating microRNAs (miRNAs) plays vital
      roles in the development of several bone diseases. However, the association
      between circulating miRNAs and steroid-induced ONFH remains elusive. MATERIALS
      AND METHODS: miRNA microarray was performed to identify the differentially
      abundant miRNAs in the serums of systemic lupus erythematosus (SLE) patients with
      steroid-induced ONFH as compared with SLE control and healthy control group. We
      predicted the potential functions of these differentially abundant miRNAs using
      Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      analyses and reconstructed the regulatory networks of miRNA-mRNA interactions.
      RESULTS: Our data indicated that there were 11 differentially abundant miRNAs (2
      upregulated and 9 downregulated) between SLE-ONFH group and healthy control group
      and 42 differentially abundant miRNAs (14 upregulated and 28 downregulated)
      between SLE-ONFH group and SLE control group. We also predicted the potential
      functions of these differentially abundant miRNAs using Gene Ontology (GO) and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and reconstructed
      the regulatory networks of miRNA-mRNA interactions. CONCLUSIONS: These findings
      corroborated the idea that circulating miRNAs play significant roles in the
      development of ONFH and may serve as diagnostic markers and therapeutic targets.

PMID- 29205601
TI  - Criteria for gauging response to sodium oxybate for narcolepsy.
AB  - Our objective was to define responder criteria using an anchor-based approach for
      frequency of cataplexy attacks and excessive daytime sleepiness in patients with
      narcolepsy undergoing sodium oxybate treatment. We used pooled data from two
      randomized, placebo-controlled, double-blind, multicentre 4- and 8-week trials of
      sodium oxybate for narcolepsy with cataplexy and analysed using receiver operator
      characteristics analysis. The percentage change in frequency of weekly cataplexy
      attacks and the Epworth Sleepiness Scale outcomes were compared with Clinical
      Global Impression of Change ratings, used as the anchor to define true response.
      Participants (n = 336) were 39% male, 89% white, with a mean age of 41.5 (15.3)
      years, reporting a median of 20.5 cataplexy attacks per week and a mean Epworth
      Sleepiness score of 17.5 at baseline. A majority (51%) were Much Improved or Very
      Much Improved based on Clinical Global Impression of Change ratings, considered a
      true response to treatment. Area under the curve values for % reduction in
      cataplexy attacks (77%) and % change in sleepiness score (78%) supported response
      definition thresholds of 46% and 12%, respectively. Classification using either
      response definition agreed with the anchor for approximately 71% of participants.
      Cataplexy response definition was more sensitive (cataplexy = 0.77, Epworth
      Sleepiness Scale = 0.69), while sleepiness was more specific (cataplexy = 0.66,
      Epworth Sleepiness Scale = 0.75). Both responder definitions showed a dose
      response relationship with sodium oxybate, demonstrating their validity using an
      external criterion. Weekly cataplexy attacks and Epworth Sleepiness Scale can be
      used to help document clinical response to narcolepsy treatment using criteria of
      46% and 12% reductions, respectively.

PMID- 29205602
TI  - Workplace violence against nurses in Korea and its impact on professional quality
      of life and turnover intention.

PMID- 29205603
TI  - Selective Profiling of Saponins from Gypsophila trichotoma Wend. by HILIC
      Separation and HRMS Detection.
AB  - INTRODUCTION: Roots of Gypsophila trichotoma Wend. (Caryophyllaceae) are rich
      sources of glucuronide oleanane-type triterpenoid carboxylic acid 3,28-O
      bidesmosides (GOTCABs). These saponins have been reported to possess synergistic
      cytotoxicity in combination with type I ribosome-inactivating protein saporin.
      OBJECTIVE: To develop ultra high-performance liquid chromatography - electrospray
      ionisation/high resolution mass spectrometry (UHPLC-ESI/HRMS) acquisition
      strategy for the recognition of Gypsophila GOTCAB saponins. METHODOLOGY: A highly
      selective hydrophilic interaction UHPLC method (Si-HILIC UHPLC) was developed for
      the separation of GOTCAB saponins from the methanol-aqueous root extract of G.
      trichotoma (GTR). UHPLC was coupled to an Orbitrap mass spectrometer equipped
      with heated electrospray ionisation (HESI) probe. ESI-HRMS and tandem mass
      spectrometry (MS/MS) data of the separated compounds was used for saponins
      structure assignment. RESULTS: Based on the conformity of the fragmentation of 11
      previously identified GTR saponins, 21 GOTCAB forming between two and four
      isobaric and positional isomers are identified with proposals for their
      structures. Tables with assignment of characteristic fragment ions and more than
      10 newly identified saponins in GTR were described. Fragmentation rules for
      tentative identification of three major types of saponins from GTR were
      summarised and possible fragmentation pathways were proposed. Type I and II
      consisted of acylated and sulphated GOTCABs, respectively, while type III
      included acylated and sulphated saponins. The type II sulphated GOTCAB saponins
      were all previously not described. CONCLUSIONS: The study demonstrates the
      potential of the coupling of highly-selective (Si)-HILIC UHPLC with HRMS and
      MS/MS detection for analysis and identification of triterpenoid saponins.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29205605
TI  - Coaching parents to assess and treat self-injurious behaviour via telehealth.
AB  - The application of telehealth technology to conduct functional analysis (FA) and
      functional communication training (FCT) is emerging for children with
      developmental disabilities and behaviour support needs. The current study was
      designed to extend FA + FCT for self-injurious behaviour by using telehealth in
      home with parents as interventionists receiving real-time remote coaching. Two
      families with school-aged boys with developmental disabilities associated with
      intellectual disability participated, one with cerebral palsy and the other with
      autism spectrum disorder. Results indicated that parent-implemented FA + FCT via
      telehealth was effective for reducing self-injurious behaviour and increasing
      mands (communication requests) for both children. Both families successfully
      implemented the FA + FCT protocol with 95% overall fidelity via telehealth
      supported coaching. Results are discussed in terms of their relationship to
      previous research, limitations and future directions.

PMID- 29205606
TI  - Abstracts of the Royal Pharmaceutical Society (RPS) Winter Summit 2017, London,
      UK, 5 December 2017.

PMID- 29205604
TI  - The role of water in plant-microbe interactions.
AB  - Throughout their life plants are associated with various microorganisms,
      including commensal, symbiotic and pathogenic microorganisms. Pathogens are
      genetically adapted to aggressively colonize and proliferate in host plants to
      cause disease. However, disease outbreaks occur only under permissive
      environmental conditions. The interplay between host, pathogen and environment is
      famously known as the 'disease triangle'. Among the environmental factors,
      rainfall events, which often create a period of high atmospheric humidity, have
      repeatedly been shown to promote disease outbreaks in plants, suggesting that the
      availability of water is crucial for pathogenesis. During pathogen infection,
      water-soaking spots are frequently observed on infected leaves as an early
      symptom of disease. Recent studies have shown that pathogenic bacteria dedicate
      specialized virulence proteins to create an aqueous habitat inside the leaf
      apoplast under high humidity. Water availability in the apoplastic environment,
      and probably other associated changes, can determine the success of potentially
      pathogenic microbes. These new findings reinforce the notion that the fight over
      water may be a major battleground between plants and pathogens. In this article,
      we will discuss the role of water availability in host-microbe interactions, with
      a focus on plant-bacterial interactions.

PMID- 29205608
TI  - In-utero aspiration vs expectant management of anechoic fetal ovarian cysts: open
      randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy and safety of in-utero aspiration (IUA) of
      anechoic fetal ovarian cysts. METHODS: This multicenter, prospective, randomized
      open trial in two parallel groups included women from nine outpatient fetal
      medicine departments with singleton pregnancy >= 28 weeks of gestation and a
      female fetus with an ultrasound-diagnosed simple ovarian cyst, defined as a
      single fully anechoic cystic structure measuring >= 30 mm. They were allocated
      randomly to IUA under ultrasound guidance or expectant management. All procedures
      were performed by trained senior obstetricians. Primary outcome was need for
      neonatal intervention, by laparoscopy, laparotomy or transabdominal aspiration.
      Secondary outcomes were in-utero involution of the cyst and oophorectomy at
      birth. Analyses were conducted according to the intention-to-treat principle.
      RESULTS: Of 61 participants, 34 were allocated to IUA and 27 to expectant
      management. Three IUA procedures (9%) could not be performed (one due to fetal
      position and two due to aspirations being dry). The remaining 31 IUA procedures
      were uneventful. The incidence of neonatal intervention did not differ
      significantly between the IUA and the expectant management groups (20.6% vs
      37.0%; relative risk (RR), 0.55; 95% CI, 0.24-1.27). Nonetheless, IUA was
      associated with increased incidence of in-utero involution of the cyst (47.1% vs
      18.5%; RR, 2.54; 95% CI, 1.07-6.05) and reduced rate of oophorectomy (3.0% vs
      22.0%; RR, 0.13; 95% CI, 0.02-1.03) compared with expectant management.
      CONCLUSION: IUA of anechoic fetal ovarian cysts, compared with expectant
      management, was not associated with a reduction in overall neonatal interventions
      but was associated with a reduced oophorectomy rate. Copyright (c) 2017 ISUOG.
      Published by John Wiley & Sons Ltd.

PMID- 29205610
TI  - Three-dimensional morphology and volume of the free Achilles tendon at rest and
      under load in people with unilateral mid-portion Achilles tendinopathy.
AB  - NEW FINDINGS: What is the central question of this study? The aim was to
      determine the effect of mid-portion Achilles tendinopathy (MAT) on free Achilles
      tendon three-dimensional morphology and volume at rest and under load in people
      with unilateral MAT. What is the main finding and its importance? Tendinopathic
      tendon had a larger resting tendon cross-sectional area and anteroposterior
      diameter relative to healthy tendon. When loaded, tendinopathic tendon
      experienced a reduction in transverse morphology (i.e. cross-sectional area,
      anteroposterior and mediolateral diameters) and overall volume reduction. In
      contrast, the healthy tendon remained isovolumetric and bulged along the
      anteroposterior axis. These findings suggest a fundamental reorganization of
      tendinopathic tendon matrix components and altered tendon fluid content when
      under load. ABSTRACT: Mid-portion Achilles tendinopathy (MAT) adversely affects
      free Achilles tendon (AT) structure and composition. However, it is not known how
      these pathological alterations associated with MAT change the normal three
      dimensional (3-D) morphology of free AT at rest and under load throughout the
      entire free tendon length. Here, we used 3-D ultrasound to examine the effect of
      unilateral MAT on free tendon 3-D morphology [length, cross-sectional area (CSA),
      anteroposterior (AP) diameter and mediolateral (ML) diameter] and volume at rest
      and during a submaximal (50%) voluntary isometric plantarflexion contraction
      bilaterally in individuals with unilateral MAT (n = 10) compared with a matched
      healthy control group (n = 10). The tendinopathic free AT had a greater CSA
      relative to the control tendons along the entire tendon length, which was mainly
      driven by a greater tendon AP diameter. Under load, the tendinopathic tendon
      experienced greater longitudinal and transverse strains than the control tendons.
      In contrast to the control tendons, which experienced a reduction in tendon CSA
      and ML diameter, bulged along the AP axis and behaved isovolumetrically under
      load, the tendinopathic tendon experienced a reduction in tendon CSA, AP diameter
      and ML diameter and an overall volume reduction. Overall, these findings suggest
      that the magnitude of longitudinal strain and volume change and the corresponding
      magnitude and direction of transverse strain under load are altered in MAT
      compared with normal tendon. These findings are indicative of a fundamental
      reorganization of the tendon matrix and alterations in tendon fluid content and
      distribution under load in tendinopathic tendon.

PMID- 29205611
TI  - Return-to-work intervention during cancer treatment - The providers' experiences.
AB  - To explore in-depth understanding of providers' experiences when involved in a
      return-to-work (RTW) intervention offered during cancer treatment. Semi
      structured individual interviews and participant observations at a hospital
      department and two municipal job centers were carried out, including ten
      providers (physicians, nurses and social workers). A phenomenological-hermeneutic
      approach was applied, involving coding, identification of themes and
      interpretation of findings. Three major themes were identified: Treatment first,
      Work as an integrated component in cancer rehabilitation, and Challenges in
      bringing up work issues. Differences in providers' experiences of the RTW
      intervention offered to cancer patients were found: in the hospital setting RTW
      was a second priority, whereas in the municipality job centers it was an
      integrated component. Further studies are needed to investigate how and when
      occupational rehabilitation services can be implemented across sectors to support
      cancer patients' RTW. In the future, work issues ought to be systematically
      presented by providers across sectors as early as possible to support cancer
      patients' RTW. Cancer patients' individual needs and thoughts about RTW are to be
      identified by both health care providers during treatment and social workers at
      the municipality level and shared across sectors.

PMID- 29205609
TI  - Effect of tamoxifen on fibrosis, collagen content and transforming growth factor
      beta1, -beta2 and -beta3 expression in common bile duct anastomosis of pigs.
AB  - End-to-end anastomosis in the treatment for bile duct injury during laparoscopic
      cholecystectomy has been associated with stricture formation. The aim of this
      study was to experimentally investigate the effect of oral tamoxifen (tmx)
      treatment on fibrosis, collagen content and transforming growth factor-beta1, 
      beta2 and -beta3 expression in common bile duct anastomosis of pigs. Twenty-six
      pigs were divided into three groups [sham (n = 8), control (n = 9) and tmx (n =
      9)]. The common bile ducts were transected and anastomosed in the control and tmx
      groups. Tmx (40 mg/day) was administered orally to the tmx group, and the animals
      were euthanized after 60 days. Fibrosis was analysed by Masson's trichrome
      staining. Picrosirius red was used to quantify the total collagen content and
      collagen type I/III ratio. mRNA expression of transforming growth factor (TGF)
      beta1, -beta2 and -beta3 was quantified using real-time polymerase chain reaction
      (qRT-PCR). The control and study groups exhibited higher fibrosis than the sham
      group, and the study group showed lower fibrosis than the control group (P =
      0.011). The control and tmx groups had higher total collagen content than the
      sham group (P = 0.003). The collagen type I/III ratio was higher in the control
      group than in the sham and tmx groups (P = 0.015). There were no significant
      differences in the mRNA expression of TGF-beta1, -beta2 and -beta3 among the
      groups (P > 0.05). Tmx decreased fibrosis and prevented the change in collagen
      type I/III ratio caused by the procedure.

PMID- 29205612
TI  - Homeodomain-interacting protein kinase phosphorylates the Drosophila Paired box
      protein 6 (Pax6) homologues Twin of eyeless and Eyeless.
AB  - Homeodomain-interacting protein kinase (Hipk), the Drosophila homologue of
      mammalian HIPK2, plays several important roles in regulating differentiation,
      proliferation, apoptosis, and stress responses and acts as a mediator for signals
      of diverse pathways, such as Notch or Wingless signalling. The Paired box protein
      6 (Pax6) has two Drosophila homologues, Twin of eyeless (Toy) and Eyeless (Ey).
      Both stand atop the retinal determination gene network (RDGN), which is essential
      for proper eye development in Drosophila. Here, we set Hipk and the master
      regulators Toy and Ey in an enzyme-substrate relationship. Furthermore, we prove
      a physical interaction between Toy and Hipk in vivo using bimolecular
      fluorescence complementation. Using in vitro kinase assays with different
      truncated Toy constructs and mutational analyses, we mapped four Hipk
      phosphorylation sites of Toy, one in the paired domain (Ser121 ) and three in the
      C-terminal transactivation domain of Toy (Thr395 , Ser410 and Thr452 ). The
      interaction and phosphorylation of the master regulator Toy by Hipk may be
      important for precise tuning of signalling within the RDGN and therefore for
      Drosophila eye development.

PMID- 29205613
TI  - Survival of extensive restorations in primary molars: 15-year practice-based
      study.
AB  - BACKGROUND: Caries decline in the western world is accompanied by strong
      polarization among children; 8% of Finnish 5-year-olds having 76% of untreated
      caries. This high caries risk group needs preventive and restorative strategies.
      AIM: To explore survival of extensive restorations in primary molars. DESIGN:
      This study was based on health records from 2002 to 2016 of children under 18
      years. RESULTS: Of severely affected primary molars (n = 1061), 41% were restored
      with preformed metal crowns (PMCs), 38% with glass-ionomer cement (GIC)/polyacid
      modified resin composite (PAMRC)/resin-modified GIC (RMGIC), and 21% with resin
      composites (RC). Younger children (3-8) received 97% of the PMCs and 86% of
      GIC/PAMRC/RMGIC; older ones (>=9) 91% of the RC restorations. Neither amalgam nor
      indirect restorations were registered. General dentists (GDs) engaged in primary
      care restored with GIC/PAMRC/RMGIC (52%) or RC (48%). GDs in general anesthesia
      care service placed 66% and specializing/specialized dentists 31% of PMCs. PMCs
      had lower failure rate (1.4% vs 3.0%) than GIC/PAMRC/RMGIC (P = 0.001). Choosing
      PMCs reduced patient visits compared to other restorations (P < 0.001).
      CONCLUSIONS: Severely affected primary molars of children at high caries risk are
      better managed, using PMCs to optimize the resources in public oral health
      services.

PMID- 29205614
TI  - Toxicity: exploring and expanding the concept.

PMID- 29205615
TI  - Evaluation of tramline sign for prenatal diagnosis of abnormally invasive
      placenta using three-dimensional ultrasound and Crystal Vue rendering technology.

PMID- 29205616
TI  - Moving beyond vaping as a cessation-only practice.

PMID- 29205617
TI  - Epigenetic states of donor cells significantly affect the development of somatic
      cell nuclear transfer (SCNT) embryos in pigs.
AB  - The type and pattern of epigenetic modification in donor cells can significantly
      affect the developmental competency of somatic cell nuclear transfer (SCNT)
      embryos. Here, we investigated the developmental capacity, gene expression, and
      epigenetic modifications of SCNT embryos derived from porcine bone marrow-derived
      mesenchymal stem cells (BMSCs) and fetal fibroblasts (FFs) donor cells compared
      to embryos obtained from in vitro fertilization (IVF). Compared to FFs, the donor
      BMSCs had more active epigenetic markers (Histone H3 modifications: H3K9Ac,
      H3K4me3, and H3K4me2) and fewer repressive epigenetic markers (H3K9me3, H3K9me2,
      and DNA methyltransferase 1). Embryos derived from BMSC nuclear-transfer (BMSC-NT
      embryos) and IVF embryos had significantly higher cleavage and blastocyst rates
      (BMSC-NT: 71.3 +/- 3.4%, 29.1 +/- 2.3%; IVF: 69.2 +/- 2.2%, 30.2 +/- 3.3%;
      respectively) than FF-NT embryos (58.1 +/- 3.4%, 15.1 +/- 1.5%, respectively).
      Bisulfite sequencing revealed that DNA methylation at the promoter regions of
      NANOG and POU5F1 was lower in BMSC-NT embryos (30.0%, 9.8%, respectively) than
      those in FF-NT embryos (34.2%, 28.0%, respectively). We also found that BMSC-NT
      embryos had more H3K9Ac and less H3K9me3 and 5-methylcytosine than FF-NT embryos.
      In conclusion, our finding comparing BMSCs versus FFs as donors for nuclear
      transfer revealed that differences in the initial epigenetic state of donor cells
      have a remarkable effect on overall nuclear reprogramming of SCNT embryos,
      wherein donor cells possessing a more open chromatin state are more conducive to
      nuclear reprogramming.

PMID- 29205618
TI  - Different responses of spontaneous and stimulus-related alpha activity to ambient
      luminance changes.
AB  - Alpha oscillations are particularly important in determining our percepts and
      have been implicated in fundamental brain functions. Oscillatory activity can be
      spontaneous or stimulus-related. Furthermore, stimulus-related responses can be
      phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity
      can be identified as the average amplitude changes in response to a stimulation,
      while phase-locked activity can be measured via reverse-correlation techniques
      (echo function). However, the mechanisms and the functional roles of these
      oscillations are far from clear. Here, we investigated the effect of ambient
      luminance changes, known to dramatically modulate neural oscillations, on
      spontaneous and stimulus-related alpha. We investigated the effect of ambient
      luminance on EEG alpha during spontaneous human brain activity at rest
      (experiment 1) and during visual stimulation (experiment 2). Results show that
      spontaneous alpha amplitude increased by decreasing ambient luminance, while
      alpha frequency remained unaffected. In the second experiment, we found that
      under low-luminance viewing, the stimulus-related alpha amplitude was lower, and
      its frequency was slightly faster. These effects were evident in the phase-locked
      part of the alpha response (echo function), but weaker or absent in the induced
      (non-phase-locked) alpha responses. Finally, we explored the possible behavioural
      correlates of these modulations in a monocular critical flicker frequency task
      (experiment 3), finding that dark adaptation in the left eye decreased the
      temporal threshold of the right eye. Overall, we found that ambient luminance
      changes impact differently on spontaneous and stimulus-related alpha expression.
      We suggest that stimulus-related alpha activity is crucial in determining human
      temporal segmentation abilities.

PMID- 29205619
TI  - BAPTA-AM dramatically improves maturation and development of bovine oocytes from
      grade-3 cumulus-oocyte complexes.
AB  - Intracellular free calcium ([Ca2+ ]i ) is essential for oocyte maturation and
      early embryonic development. Here, we investigated the role of [Ca2+ ]i in
      oocytes from cumulus-oocyte complexes (COCs) with respect to maturation and early
      embryonic development, using the calcium-buffering agent BAPTA-AM (1,2-bis[2
      aminophenoxy]ethane-N,N,N',N'-tetraacetic acid tetrakis [acetoxymethyl ester]).
      COCs were graded based on compactness of the cumulus mass and appearance of the
      cytoplasm, with Grade 1 indicating higher quality and developmental potential
      than Grade 3. Results showed that: (i) [Ca2+ ]i in metaphase-II (MII) oocytes
      from Grade-3 COCs was significantly higher than those from Grade-1 COCs, and was
      significantly reduced by BAPTA-AM; (ii) nuclear maturation of oocytes from Grade
      3 COCs treated with BAPTA-AM was enhanced compared to untreated COCs; (iii)
      protein abundance of Cyclin B and oocyte-specific Histone 1 (H1FOO) was improved
      in MII oocytes from Grade-3 COCs treated with BAPTA-AM; (iv) Ca2+ transients were
      triggered in each group upon fertilization, and the amplitude of [Ca2+ ]i
      oscillations increased in the Grade-3 group upon treatment with BAPTA-AM, with
      the magnitude approaching that of the Grade-1 group; and (v) cleavage rates and
      blastocyst-formation rates were improved in the Grade-3 group treated with BAPTA
      AM compared to untreated controls following in vitro fertilization and
      parthenogenetic activation. Therefore, BAPTA-AM dramatically improved oocyte
      maturation, oocyte quality, and embryonic development of oocytes from Grade-3
      COCs.

PMID- 29205620
TI  - Interobserver reliability of computed tomographic contouring of canine tonsils in
      radiation therapy treatment planning.
AB  - In radiation therapy (RT) treatment planning for canine head and neck cancer, the
      tonsils may be included as part of the treated volume. Delineation of tonsils on
      computed tomography (CT) scans is difficult. Error or uncertainty in the volume
      and location of contoured structures may result in treatment failure. The purpose
      of this prospective, observer agreement study was to assess the interobserver
      agreement of tonsillar contouring by two groups of trained observers. Thirty dogs
      undergoing pre- and post-contrast CT studies of the head were included. After the
      pre- and postcontrast CT scans, the tonsils were identified via direct
      visualization, barium paste was applied bilaterally to the visible tonsils, and a
      third CT scan was acquired. Data from each of the three CT scans were registered
      in an RT treatment planning system. Two groups of observers (one veterinary
      radiologist and one veterinary radiation oncologist in each group) contoured
      bilateral tonsils by consensus, obtaining three sets of contours. Tonsil volume
      and location data were obtained from both groups. The contour volumes and
      locations were compared between groups using mixed (fixed and random effect)
      linear models. There was no significant difference between each group's contours
      in terms of three-dimensional coordinates. However there was a significant
      difference between each group's contours in terms of the tonsillar volume (P <
      0.0001). Pre- and postcontrast CT can be used to identify the location of canine
      tonsils with reasonable agreement between trained observers. Discrepancy in
      tonsillar volume between groups of trained observers may affect RT treatment
      outcome.

PMID- 29205621
TI  - Multiparametric characterization of response to anti-angiogenic therapy using
      USPIO contrast-enhanced MRI in combination with dynamic contrast-enhanced MRI.
AB  - BACKGROUND: Steady state susceptibility contrast (SSC)-MRI provides information
      on vascular morphology but is a rarely used method. PURPOSE: To investigate the
      utility of the ultrasmall superparamagnetic iron oxide particles (USPIOs)
      GEH121333 for measuring tumor response to bevacizumab and compare this with
      gadolinium-based DCE-MRI. STUDY TYPE: Prospective preclinical animal model study.
      ANIMAL MODEL: Mice bearing subcutaneous TOV-21G human ovarian cancer xenografts
      treated with bevacizumab (n = 9) or saline (n = 9). FIELD STRENGTH/SEQUENCE:
      Imaging was performed on a 7T Bruker Biospec. For SSC-MRI with GEH121333 we
      acquired R1 -maps (RARE-sequence with variable TR), R2 -maps (multi-spin echo),
      and R2*-maps (multi-gradient echo). Additionally, R1 and R2 maps were measured on
      the days after USPIO injection. For DCE-MRI with gadodiamide we acquired 200 T1 
      weighted images (RARE-sequence). ASSESSMENT: DeltaR1 , DeltaR2 , and DeltaR2*
      maps were computed from SSC-MRI. DCE-MRI was analysed using the extended Tofts
      model. STATISTICAL TESTS: Results from pre- and 3 days posttreatment SSC-MRI were
      compared using paired-sample t-tests. Treatment and control groups were compared
      using independent sample t-tests. Performance of SSC- and DCE-MRI was compared
      using multivariate partial least squares discriminant analysis. RESULTS: Already
      one day after treatment and USPIO injection, R1 and R2 values were lower in
      treated (R1  = 0.49 +/- 0.03s-1 , R2  = 23.07 +/- 1.49s-1 ) compared with control
      tumors (R1  = 0.52 +/- 0.02s-1 , R2  = 24.98 +/- 1.01s-1 ), indicating lower
      USPIO accumulation. Posttreatment SSC-MRI displayed significantly decreased tumor
      blood volume (change in DeltaR2  = -0.43 +/- 0.26s-1 , P = 0.001) and vessel
      density (change in Q = -0.032 +/- 0.020s-1/3 , P = 0.002). DCE-MRI showed among
      others lower Ktrans in treated tumors (control = 0.064 +/- 0.011min-1 , tx =
      0.046 +/- 0.008min-1 , P = 0.002). Multivariate analysis suggests that SSC-MRI
      was slightly inferior to DCE-MRI in distinguishing treated from control tumors
      (accuracy = 75%, P = 0.058 versus 80%, P = 0.028), but a combination of both was
      best (accuracy = 85%; P = 0.003). DATA CONCLUSION: SSC-MRI with GEH121333 is
      sensitive to early (<24 h) and late changes in tumor vasculature. SSC-MRI and DCE
      MRI provide complementary information and can be used to assess different aspects
      of vascular responses to anti-angiogenic therapies. LEVEL OF EVIDENCE: 1
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1589-1600.

PMID- 29205622
TI  - Radiographic features of congenital segmental dilation of the intestine in a
      german shepherd dog.
AB  - A 10-week-old spayed female German Shepherd Dog was presented for acute vomiting
      and diarrhea. There was no reported foreign body or toxin ingestion. Radiographs
      showed a severely (~11 * 7 cm), focally distended right abdominal intestinal
      segment containing gas and soft tissue material. Other small intestinal segments
      were segmentally gas distended. Celiotomy identified a ~9 cm focally dilated
      segment at the jejunoileal junction with no aborad luminal obstruction. Resection
      and anastomosis of the dilation was performed. Histopathology showed mild mucosal
      inflammation, but otherwise normal wall layering and autonomic ganglia.
      Radiographic and histopathologic findings were consistent with congenital
      segmental dilation of the intestine.

PMID- 29205623
TI  - Improvement of the repeatability of parallel transmission at 7T using interleaved
      acquisition in the calibration scan.
AB  - BACKGROUND: Respiration-induced phase shift affects B0 /B1+ mapping repeatability
      in parallel transmission (pTx) calibration for 7T brain MRI, but is improved by
      breath-holding (BH). However, BH cannot be applied during long scans. PURPOSE: To
      examine whether interleaved acquisition during calibration scanning could improve
      pTx repeatability and image homogeneity. STUDY TYPE: Prospective. SUBJECTS: Nine
      healthy subjects. FIELD STRENGTH/SEQUENCE: 7T MRI with a two-channel RF
      transmission system was used. ASSESSMENT: Calibration scanning for B0 /B1+
      mapping was performed under sequential acquisition/free-breathing (Seq-FB), Seq
      BH, and interleaved acquisition/FB (Int-FB) conditions. The B0 map was calculated
      with two echo times, and the B1+ map was obtained using the Bloch-Siegert method.
      Actual flip-angle imaging (AFI) and gradient echo (GRE) imaging were performed
      using pTx and quadrature-Tx (qTx). All scans were acquired in five sessions.
      Repeatability was evaluated using intersession standard deviation (SD) or
      coefficient of variance (CV), and in-plane homogeneity was evaluated using in
      plane CV. STATISTICAL TESTS: A paired t-test with Bonferroni correction for
      multiple comparisons was used. RESULTS: The intersession CV/SDs for the B0 /B1+
      maps were significantly smaller in Int-FB than in Seq-FB (Bonferroni-corrected P
      < 0.05 for all). The intersession CVs for the AFI and GRE images were also
      significantly smaller in Int-FB, Seq-BH, and qTx than in Seq-FB (Bonferroni
      corrected P < 0.05 for all). The in-plane CVs for the AFI and GRE images in Seq
      FB, Int-FB, and Seq-BH were significantly smaller than in qTx (Bonferroni
      corrected P < 0.01 for all). DATA CONCLUSION: Using interleaved acquisition
      during calibration scans of pTx for 7T brain MRI improved the repeatability of B0
      /B1+ mapping, AFI, and GRE images, without BH. LEVEL OF EVIDENCE: 1 Technical
      Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

PMID- 29205624
TI  - Fundamental movement skills and balance of children with Down syndrome.
AB  - BACKGROUND: Conclusive evidence supports the importance of fundamental movement
      skills (FMS) proficiency in promoting physical activity and countering obesity.
      In children with Down Syndrome (DS), FMS development is delayed, which has been
      suggested to be associated with balance deficits. This study therefore examined
      the relationship between FMS proficiency and balance ability in children with DS,
      with the aim of contributing evidence to programmes that address FMS delay.
      METHODS: Participants consisted of 20 children with DS (7.1 +/- 2.9 years old)
      and an age-matched control group of children with typical development (7.25 +/-
      2.5 years). In the first part of the study, FMS (i.e. locomotor and object
      control) proficiency of the children was tested using the Test of Gross Motor
      Development-2. Balance ability was assessed using a force platform to measure
      centre of pressure average velocity (AV; mm/sec), path length (mm), medio-lateral
      standard deviation (mm) and antero-posterior standard deviation (mm). In the
      second part of the study, children with DS participated in 5 weeks of FMS
      training. FMS proficiency and balance ability were tested post-training and
      compared to pre-training scores. Verbal and visuo-spatial short-term memory
      capacities were measured at pre-training to verify the role of working memory in
      skill learning. RESULTS: FMS proficiency was associated with centre of pressure
      parameters in children with DS but not in children with typical development.
      After controlling for age, AV was found to predict significant variance in
      locomotor (R2  = 0.61, P < 0.001) and object control (R2  = 0.69, P < 0.001)
      scores. FMS proficiency and mastery improved after FMS training, as did AV, path
      length and antero-posterior standard deviation (all P < 0.05). Verbal and visuo
      spatial short-term memory did not interact with the effects of training.
      CONCLUSIONS: Children with DS who have better balance ability tend to have more
      proficient FMS. Skill-specific training improved not only FMS sub-skills but
      static balance stability as well. Working memory did not play a role in the
      changes caused by skills training. Future research should examine the causal
      relationship between balance and FMS.

PMID- 29205625
TI  - Vitamin D facilitates trophoblast invasion through induction of epithelial
      mesenchymal transition.
AB  - PROBLEM: Vitamin D deficiency increases the risk of developing pregnancy-related
      complications, including preeclampsia and small-for-gestational-age infants.
      Vitamin D was demonstrated to promote the invasiveness of human extravillous
      trophoblasts (EVTs). However, whether vitamin D induces the epithelial
      mesenchymal transition (EMT) of EVTs remains unclear. Therefore, we investigated
      whether vitamin D promotes EMT and the related signaling pathways. METHOD OF
      STUDY: In this study, we performed EMT experiments using JAR cells based on the
      expression of the mesenchymal markers and vitamin D receptor. JAR cells were
      treated with calcitriol, the active form of vitamin D. Western blotting was
      performed to evaluate EMT markers and key molecules of signaling pathways.
      Invasion assays were conducted. Expression and secretion of MMPs were analyzed by
      real-time PCR and zymography. RESULTS: Calcitriol significantly enhanced EMT and
      the invasive capability of JAR cells, along with increased expression and
      secretion of MMP-2 and MMP-9. Moreover, ERK signaling pathway was activated by
      calcitriol. The effects of calcitriol were neutralized by ERK signaling blocker.
      CONCLUSION: Calcitriol facilitated EMT induction and expression of MMPs via ERK
      signaling pathway, which promoted the invasive capability of EVTs. Further
      studies are warranted to elucidate the potential application of vitamin D in the
      prevention of pregnancy complications.

PMID- 29205626
TI  - Feasibility and reproducibility of feature-tracking-based strain and strain rate
      measures of the left ventricle in different diseases and genders.
AB  - BACKGROUND: The measurement of myocardial deformation by strain analysis is an
      evolving tool to quantify regional and global myocardial function. PURPOSE: To
      assess the feasibility and reproducibility of myocardial strain/strain rate
      measurements with magnetic resonance feature tracking (MR-FT) in healthy subjects
      and in patient groups. STUDY TYPE: Prospective study. POPULATION: Sixty patients
      (20 hypertensives with left ventricular (LV) hypertrophy (H); 20 nonischemic
      dilated cardiomyopathy (D); 20 ischemic heart disease (I); as well as 20 controls
      (C) were included, 10 men and 10 women in each group. FIELD STRENGTH/SEQUENCE: A
      1.5T MR protocol including steady-state free precession (SSFP) cine sequences in
      the standard views and late enhancement sequences. ASSESSMENT: LV volumes, mass,
      global and regional radial, circumferential, and longitudinal strain/strain rate
      were measured using CVI42 software. The analysis time was recorded. STATISTICAL
      TESTS: Intraobserver and interobserver agreement and intraclass correlation
      coefficients (ICC) were obtained for reproducibility assessment as well as
      differences according to gender and group of pertinence. RESULTS: Strain/strain
      rate analysis could be achieved in all subjects. The average analysis time was 14
      +/- 3 minutes. The average intraobserver ICC was excellent (ICC >0.90) for strain
      and good (ICC >0.75) for strain rate. Reproducibility of strain measurements was
      good to excellent (ICC >0.75) for all groups of subjects and both genders.
      Reproducibility of strain measurements was good for basal segments (ICC >0.75)
      and excellent for middle and apical segments (ICC >0.90). Reproducibility of
      strain rate measurements was moderate for basal segments (ICC >0.50) and good for
      middle and apical segments. DATA CONCLUSION: MR-FT for strain/strain rate
      analysis is a feasible and highly reproducible technique. CVI42 FT analysis was
      equally feasible and reproducible in various pathologies and between genders.
      Better reproducibility was seen globally for middle and apical segments, which
      needs further clarification. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J.
      Magn. Reson. Imaging 2018;47:1415-1425.

PMID- 29205627
TI  - Exacerbated grassland degradation and desertification in Central Asia during 2000
      2014.
AB  - Grassland degradation and desertification is a complex process, including both
      state conversion (e.g., grasslands to deserts) and gradual within-state change
      (e.g., greenness dynamics). Existing studies hardly separated the two components
      and analyzed it as a whole based on time series vegetation index data, which
      cannot provide a clear and comprehensive picture for grassland degradation and
      desertification. Here we propose an integrated assessment strategy, by
      considering both state conversion and within-state change of grasslands, to
      investigate grassland degradation and desertification process in Central Asia.
      First, annual maps of grasslands and sparsely vegetated land were generated to
      track the state conversions between them. The results showed increasing
      grasslands were converted to sparsely vegetated lands from 2000 to 2014, with the
      desertification region concentrating in the latitude range of 43-48 degrees  N. A
      frequency analysis of grassland vs. sparsely vegetated land classification in the
      last 15 yr allowed a recognition of persistent desert zone (PDZ), persistent
      grassland zone (PGZ), and transitional zone (TZ). The TZ was identified in
      southern Kazakhstan as one hotspot that was unstable and vulnerable to
      desertification. Furthermore, the trend analysis of Enhanced Vegetation Index
      during thermal growing season (EVITGS ) was investigated in individual zones
      using linear regression and Mann-Kendall approaches. An overall degradation
      across the area was found; moreover, the second desertification hotspot was
      identified in northern Kazakhstan with significant decreasing in EVITGS , which
      was located in PGZ. Finally, attribution analyses of grassland degradation and
      desertification were conducted by considering precipitation, temperature, and
      three different drought indices. We found persistent droughts were the main
      factor for grassland degradation and desertification in Central Asia. Considering
      both state conversion and gradual within-state change processes, this study
      provided reference information for identification of desertification hotspots to
      support further grassland degradation and desertification treatment, and the
      method could be useful to be extended to other regions.

PMID- 29205628
TI  - Clinical Neuroimaging Using 7 T MRI: Challenges and Prospects.
AB  - The aim of this article is to illustrate the principal challenges, from the
      medical and technical point of view, associated with the use of ultrahigh field
      (UHF) scanners in the clinical setting and to present available solutions to
      circumvent these limitations. We would like to show the differences between UHF
      scanners and those used routinely in clinical practice, the principal advantages,
      and disadvantages, the different UHFs that are ready be applied to routine
      clinical practice such as susceptibility-weighted imaging, fluid-attenuated
      inversion recovery, 3-dimensional time of flight, magnetization-prepared rapid
      acquisition gradient echo, magnetization-prepared 2 rapid acquisition gradient
      echo, and diffusion-weighted imaging, the technical principles of these
      sequences, and the particularities of advanced techniques such as diffusion
      tensor imaging, spectroscopy, and functional imaging at 7TMR. Finally, the main
      clinical applications in the field of the neuroradiology are discussed and the
      side effects are reported.

PMID- 29205629
TI  - Fake news. Fake journals. Fake conferences. What we can do.

PMID- 29205630
TI  - Health-care professionals' approach in feeding term small-for-gestational age
      infants and its potential implications to later growth outcomes.
AB  - AIM: To understand feeding practices, nutrition management and postnatal growth
      monitoring of term small-for-gestational age (tSGA) infants in Southeast Asia.
      METHODS: Anonymous questionnaires to assess practices on feeding, nutrition
      management and post-natal growth monitoring of tSGA infants were distributed
      among health-care professionals (HCPs) participating in regional/local
      perinatology symposia in Malaysia, Thailand and Singapore. RESULTS: Three hundred
      seventy-seven respondents from Malaysia (37%), Thailand (27%), Singapore (18%)
      and other Asian countries (19%) participated in the survey. Respondents were
      neonatologists (35%), paediatricians (25%) and other HCPs (40%) including nurses
      and midwives. Exclusive human milk feeding was reported the most preferred
      feeding option for tSGA infants, followed by fortified human milk feeding (60%
      and 20%, respectively). This was consistent among the different countries. The
      perceived nutrient requirements of tSGA infants varied between countries. Most
      respondents from Malaysia and Singapore reported requirements to be similar to
      preterm infants, while the majority from Thailand reported that it was less than
      those of preterm infants. The World Health Organization Growth Chart of 2006 and
      Fenton Growth Charts of 2013 were the most frequently used charts for growth
      monitoring in the hospital and after discharge. CONCLUSIONS: Nutrition management
      and perceived nutrient requirements for tSGA infants among practising HCPs in
      Southeast Asia showed considerable variation. The impetus to form standardised
      and evidence based feeding regimens is important as adequate nutritional
      management and growth monitoring particularly in this population of infants will
      have long term impact on population health.

PMID- 29205632
TI  - Polymer Materials and Engineering Research at Sichuan University.

PMID- 29205631
TI  - Maternal CD8+ T-cell depletion alleviates intrauterine inflammation-induced
      perinatal brain injury.
AB  - We investigated the mechanisms by which CD8+ T-cell trafficking in placenta
      contributes to perinatal brain injury by studying effects of maternal CD8+ T-cell
      depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal
      CD8+ T cells were depleted with anti-CD8+ antibodies. IUI was induced with
      lipopolysaccharide (LPS). DEP was confirmed using flow cytometry. Preterm birth
      rate was evaluated. Offspring neurologic sequelae were assessed by Nissl
      staining, immune arrays, confirmatory individual TaqMan(r) gene assays, and
      neurobehavioral tests. DEP did not significantly prevent LPS-induced preterm
      birth but improved neurobehavioral performance (P < .001) and increased cortical
      neuronal density (P < .05) in LPS-exposed pups compared to controls. These
      changes were associated with decreased CCL3 and CXCL10 and increased CCL5 in DEP
      LPS-exposed mice. We demonstrate that DEP reduces perinatal brain injury
      following IUI. This supports a role for maternal CD8+ T-cell trafficking in
      placenta in mediating perinatal brain injury separate from preterm birth
      mechanisms.

PMID- 29205633
TI  - A combined connectivity mapping and pharmacoepidemiology approach to identify
      existing medications with breast cancer causing or preventing properties.
AB  - PURPOSE: We applied a novel combined connectivity mapping and
      pharmacoepidemiological approach to identify medications that alter breast cancer
      risk. METHODS: The connectivity mapping process identified 6 potentially cancer
      causing (meloxicam, azithromycin, rizatriptan, citalopram, rosiglitazone, and
      verapamil) and 4 potentially cancer-preventing (bendroflumethiazide, sertraline,
      fluvastatin, and budesonide) medications that were suitable for
      pharmacoepidemiological investigation. Within the UK Clinical Practice Research
      Datalink, we matched 45,147 breast cancer cases to 45,147 controls based on age,
      year, and general practice. Medication use was determined from electronic
      prescribing records. We used conditional logistic regression to calculate odds
      ratios (ORs) for the association between medication use and cancer risk after
      adjustment for comorbidities, lifestyle factors, deprivation, and other
      medication use. RESULTS: Bendroflumethiazide was associated with increased breast
      cancer risk (OR: 1.11; 95% CI: 1.06, 1.15); however the connectivity mapping
      exercise predicted that this medication would reduce risk. There were no
      statistically significant associations for any of the other candidate
      medications, with ever use ORs ranging from 0.93 (95% CI: 0.78, 1.11) for
      azithromycin to 1.16 (95% CI: 0.99, 1.37) for verapamil. CONCLUSIONS: In this
      instance, our combined connectivity mapping and pharmacoepidemiological approach
      did not identify any additional medications that were substantially associated
      with breast cancer risk. This could be due to limitations in the connectivity
      mapping, such as implausible dosage requirements, or the pharmacoepidemiology,
      such as residual confounding.

PMID- 29205634
TI  - Safety and feasibility of stereotactic radiotherapy using computed portal
      radiography for canine intracranial tumors.
AB  - Stereotactic radiotherapy is a highly conformal treatment option for intracranial
      and extracranial malignancies. Stereotactic radiotherapy utilizes specialized
      equipment specifically designed to avoid normal tissue while delivering ablative
      treatments with submillimeter precision and accuracy. Linear accelerator based
      stereotactic radiotherapy incorporates on-board image guidance utilizing cone
      beam computed tomography (CT). Many institutions lack the ability to provide
      image guidance with cone beam CT but delivery of highly conformal treatments with
      submillimeter precision and accuracy is still feasible. The purpose of this
      retrospective, pilot study was to describe clinical outcomes for a group of dogs
      with neurological disease that were treated with an stereotactic radiotherapy
      technique utilizing intensity modulated radiation therapy, megavoltage computed
      portal radiography, a bite plate, thermoplastic mold, and mask based positioning
      system. Twelve dogs with neurological clinical signs were included. The diagnosis
      of intracranial tumor was made based on advanced imaging (12/12) and confirmed
      via histopathology (3/12). Twelve courses of stereotactic radiotherapy, utilizing
      three fractions of 8.0 Gy, were delivered on alternating days. Self-resolving
      neurological deterioration was observed in two patients during stereotactic
      radiotherapy. Neurological progression free interval and median survival time
      were 273 days (range: 16-692 days) and 361 days (range: 25-862 days).
      Stereotactic radiotherapy using computed portal radiography may be a safe
      treatment option for dogs with intracranial tumors.

PMID- 29205635
TI  - Cerebral White Matter Maturation Patterns in Preterm Infants: An MRI T2
      Relaxation Anisotropy and Diffusion Tensor Imaging Study.
AB  - BACKGROUND AND PURPOSE: Preterm birth is associated with worse neurodevelopmental
      outcome, but brain maturation in preterm infants is poorly characterized with
      standard methods. We evaluated white matter (WM) of infant brains at term
      equivalent age, as a function of gestational age at birth, using multimodal
      magnetic resonance imaging (MRI). METHODS: Infants born very preterm (<32 weeks
      gestation) and late preterm (33-36 weeks gestation) were scanned at 3 T at term
      equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data
      were analyzed using tract-based spatial statistics, and anisotropy of T2
      relaxation was also determined. Principal component analysis and linear
      discriminant analysis were applied to seek the variables best distinguishing very
      preterm and late preterm groups. RESULTS: Across widespread regions of WM, T2 is
      longer in very preterm infants than in late preterm ones. These effects are more
      prevalent in regions of WM that myelinate earlier and faster. Similar effects are
      obtained from DTI, showing that fractional anisotropy (FA) is lower and radial
      diffusivity higher in the very preterm group, with a bias toward earlier
      myelinating regions. Discriminant analysis shows high sensitivity and specificity
      of combined T2 relaxometry and DTI for the detection of a distinct WM development
      pathway in very preterm infants. T2 relaxation is anisotropic, depending on the
      angle between WM fiber and magnetic field, and this effect is modulated by FA.
      CONCLUSIONS: Combined T2 relaxometry and DTI characterizes specific patterns of
      retarded WM maturation, at term equivalent age, in infants born very preterm
      relative to late preterm.

PMID- 29205636
TI  - Immune checkpoint molecules soluble program death ligand 1 and galectin-9 are
      increased in pregnancy.
AB  - PROBLEM: Pregnancy requires balance between tolerance to the haploidentical fetus
      and the mother's ability to mount immune responses. There are parallels to this
      phenomenon that occur in metastatic cancer. We assessed soluble program death
      ligand-1 soluble PD-L1 (sPD-L1) and galectin-9 in the blood of pregnant women
      during gestation as these molecules are highly involved in immune suppression
      during cancer. METHOD OF STUDY: Maternal blood was collected from 30 primigravida
      women at monthly intervals during pregnancy, delivery and 6-week post-partum.
      Blood was analyzed for sPD-L1 and galectin-9 concentrations by ELISA. Term
      placentas were collected in formalin and IHC was completed for PD-L1 and galectin
      9 expression. RESULTS: Maternal blood levels of sPD-L1 (0.438 ng/mL) and galectin
      9 (1976 pg/mL) were elevated early in normal pregnancies compared to non-pregnant
      controls (0.242 ng/mL and 773 pg/mL, respectively). sPD-L1 increased throughout
      gestation, whereas galectin-9 remained elevated until parturition; both proteins
      returned to control levels post-partum. Women carrying male fetuses had
      significantly higher galectin-9 levels, but not sPD-L1, than those carrying
      females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term
      placenta coexpress galectin-9 and PD-L1. CONCLUSION: Immune-regulatory molecules
      galectin-9 and sPD-L1 increased during pregnancy and may play a role in immune
      tolerance that is critical for the fetus.

PMID- 29205637
TI  - A field guide for cancer diagnostics using cell-free DNA: From principles to
      practice and clinical applications.
AB  - Recently, many genome-wide profiling studies provided insights into the molecular
      make-up of major cancer types. The deeper understanding of these genetic
      alterations and their functional consequences led to the discovery of novel
      therapeutic opportunities improving clinical management of cancer patients. While
      tissue-based molecular patient stratification is the gold standard for precision
      medicine, it has certain limitations: Tissue biopsies are invasive sampling
      procedures carrying the risk of complications and may not represent the entire
      tumor due to underlying genetic heterogeneity. In this context, complementary
      characterization of genetic information in the blood of cancer patients can serve
      as minimal-invasive 'liquid biopsy'. Fragments of circulating cell-free DNA
      (cfDNA) are released from tissues of healthy individuals as well as cancer
      patients. The fraction of cfDNA that is released from primary tumors or
      metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in
      cancer cells, which are a potential source for diagnostic, prognostic, and
      predictive biomarkers. Recent studies have demonstrated technical feasibility and
      clinical applications including detection of drug targets and resistance
      mutations as well as longitudinal monitoring of tumors under therapy. To this
      end, a variety of pre-analytical procedures for blood processing, isolation and
      quantification of cfDNA are being employed and several analytical methods and
      technologies ranging from PCR-based single locus assays to genome-wide approaches
      are available, which considerably differ in sensitivity, specificity, and
      throughput. However, broad implementation of ctDNA analysis in daily clinical
      practice requires a thorough understanding of theoretical, technical, and
      biological concepts and necessitates standardization and validation of pre
      analytical and analytical procedures across different technologies. Here, we
      review the pertinent literature and discuss the advantages and limitations of
      available methodologies and their potential applications in molecular
      diagnostics.

PMID- 29205638
TI  - Long Noncoding RNA-1604 Orchestrates Neural Differentiation through the miR
      200c/ZEB Axis.
AB  - Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural
      differentiation is helpful not only for understanding neural development but also
      for obtaining high-quality neural progenitor cells required by stem cell therapy
      of neurodegenerative diseases. Here, we found that long noncoding RNA 1604
      (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation,
      and knockdown of lncRNA-1604 significantly repressed neural differentiation of
      mouse ESCs both in vitro and in vivo. Bioinformatics prediction and mechanistic
      analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA
      of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during
      neural differentiation. Furthermore, we also demonstrated the critical role of
      miR-200c and ZEB1/2 in mouse neural differentiation. Either introduction of miR
      200c sponge or overexpression of ZEB1/2 significantly reversed the lncRNA-1604
      knockdown-induced repression of mouse ESC neural differentiation. Collectively,
      these findings not only identified a previously unknown role of lncRNA-1604 and
      ZEB1/2 but also elucidated a new regulatory lncRNA-1604/miR-200c/ZEB axis in
      neural differentiation. Stem Cells 2018;36:325-336.

PMID- 29205639
TI  - Proton Conducting Membranes Based on Poly(Ionic Liquids) Having Phosphonium
      Counter-Cations.
AB  - Proton conducting polymeric membranes are highly searched in many different
      technologies ranging from energy to biosensing. Protic ionic liquids and their
      polymeric version represent a new family of proton conducting molecules with
      relatively facile synthesis and excellent properties. In this work, protic
      poly(ionic liquids) having the most popular phosphonium counter-cations are
      presented for the first time. The synthesis is carried out through proton
      transfer reactions or through ion exchange reactions by using commercially
      available tertiary phosphines. Tributyl-, trioctyl-, and tricyclohexyl-phosphine
      are selected to form the desired cations. Polystyrene sulfonic acid, poly(2
      acrylamido-2-methyl-1-propanesulfonic acid), and lithium poly[(4-styrenesulfonyl)
      (trifluoromethanesulfonyl)imide] polymers are used to form the polymeric anions.
      The chemical structure of the protic poly(ionic liquids) is confirmed by
      spectroscopic characterizations such as Fourier transform infrared and nuclear
      magnetic resonance spectroscopies. Thermal properties of the polymer are
      characterized by means of differential scanning calorimetry and thermogravimetric
      analysis. Polymers exhibit good membrane forming ability as well as high ionic
      conductivities in the range of 10-8 to 10-3 S cm-1 from 30 to 90  degrees C.

PMID- 29205640
TI  - Presepsin as a predictor of positive blood culture in suspected neonatal sepsis.
AB  - BACKGROUND: Although the incidence of neonatal sepsis is decreasing, neonatal
      sepsis remains a severe life-threatening disease. No current biochemical marker
      can provide perfect diagnostic accuracy for neonatal sepsis. The aim of this
      study was therefore to evaluate the accuracy of presepsin (P-SEP) as a novel
      biomarker of bacterial infection for neonatal sepsis diagnosis. METHODS: We
      prospectively studied newborns with sepsis (sepsis group; n = 13) during the
      first 30 days after birth and compared them with control preterm newborns
      (control group; n = 18). In addition, we evaluated term newborns with some
      clinical signs of early onset sepsis (non-sepsis term group; n = 35). RESULTS: P
      SEP in the sepsis group was significantly higher than in the control group (P <
      0.001) The area under the curve for P-SEP was 0.868 (95%CI: 0.71-1.00). A P-SEP
      cut-off of 795 pg/mL was established, with 85% sensitivity and 89% specificity.
      The positive and negative predictive values were 85% and 89%, respectively. In
      the non-sepsis term group, P-SEP had better stability than white blood cells and
      C-reactive protein for 3 days after birth. CONCLUSIONS: P-SEP can better
      discriminate between infections and non-infectious inflammatory conditions than
      the currently used biomarkers.

PMID- 29205641
TI  - Clinical and Arterial Spin Labeling Brain MRI Features of Transitional Venous
      Anomalies.
AB  - BACKGROUND AND PURPOSE: Transitional venous anomalies (TVAs) are rare
      cerebrovascular lesions that resemble developmental venous anomalies (DVAs), but
      demonstrate early arteriovenous shunting on digital subtraction angiography (DSA)
      without the parenchymal nidus of arteriovenous malformations (AVMs). We
      investigate whether arterial spin labeling (ASL) magnetic resonance imaging (MRI)
      can distinguish brain TVAs from DVAs and guide their clinical management.
      METHODS: We conducted a single-center retrospective review of patients with brain
      parenchymal DVA-like lesions with increased ASL signal on MRI. Clinical histories
      and follow-up information were obtained. Two readers assessed ASL signal location
      relative to the vascular lesion on MRI and, if available, the presence of
      arteriovenous shunting on DSA. RESULTS: Thirty patients with DVA-like lesions
      with increased ASL signal were identified. Clinical symptoms prompted MRI
      evaluation in 83%. Symptoms did not localize to the venous anomaly in 90%. Ten
      percent presented with acute symptoms, only one of whom presented with
      hemorrhage. ASL signal in relation to the venous anomaly was identified in: 50%
      in the adjacent parenchyma, 33% in the lesion, 7% in a distal draining
      vein/sinus, and 10% in at least two of these sites. Follow-up DSA confirmed
      arteriovenous shunting in 71% of ASL-positive venous anomalies. Interrater
      agreement was very good (kappa = .81-1.0, P < .001). CONCLUSION: A DVA-like
      lesion with increased ASL signal likely represents a TVA with arteriovenous
      shunting. Our study indicates that these lesions are usually incidentally
      detected and have a lower risk of hemorrhage than AVMs. ASL-MRI may be a useful
      tool to identify TVAs and guide further management of patients with TVAs.

PMID- 29205642
TI  - Obesity in elementary school children after the Great East Japan Earthquake.
AB  - BACKGROUND: Rikuzentakata was one of the cities most devastated by the Great East
      Japan Earthquake on 11 March 2011. Many buildings were swept away or destroyed
      and affected families were placed into temporary housing. The aim of this study
      was to determine the impact of long-term temporary housing on the body mass index
      (BMI) of elementary school children living in Rikuzentakata City. METHODS: A
      retrospective cohort study of was carried out of students attending 1st-3rd grade
      in 2010, and 4th-6th grade in 2013, in eight elementary schools in Rikuzentakata
      City. Height and weight were measured annually. We compared changes in BMI
      between children in temporary housing and those in permanent housing. Separately,
      parents of students attending one of the elementary schools were surveyed in
      2013. RESULTS: Of 526 children in the present study, 32% were living in temporary
      housing. The prevalence of obesity climbed from 5.3% in 2010 to 7.8% in 2013 in
      the temporary housing group, and from 7.6% to 7.8% in the permanent housing
      group. BMI z-score in the temporary housing group increased by 0.102 points
      between 2010 and 2013 (P < 0.02). Children in temporary housing spent more time
      reading comic books and their walking commute time had decreased by 2 min
      compared with before the disaster. CONCLUSION: Obesity prevalence and BMI z-score
      increased in children in temporary housing compared with permanent housing. A
      more sedentary lifestyle may explain this trend. It is important for policy
      makers and health-care providers to recognize potential consequences of long-term
      residence in temporary housing.

PMID- 29205643
TI  - Paternal HLA-C is a risk factor in unexplained recurrent miscarriage.
AB  - PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We
      hypothesized that the alloimmune response to paternal HLA-C plays a role in
      unexplained recurrent miscarriage. METHOD OF STUDY: In a case-control design, we
      included 100 women with at least three unexplained consecutive miscarriages along
      with their partners and children. For the first control group, we included 90
      women with an uneventful singleton pregnancy without pregnancy complications in
      their history along with their children. The second control group consisted of
      425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic
      HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA
      antibodies in the mother were determined. RESULTS: HLA-C and HLA-C*07 mismatches
      were significantly increased in couples with recurrent miscarriage compared to
      control subjects (P = .016, P = .008, respectively). The incidence of child
      specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent
      miscarriage (P = .007). CONCLUSION: The results show that HLA-C incompatibility
      between couples is significantly associated with unexplained recurrent
      miscarriage.

PMID- 29205644
TI  - Making do with less: must sparse data preclude informed harvest strategies for
      European waterbirds?
AB  - The demography of many European waterbirds is not well understood because most
      countries have conducted little monitoring and assessment, and coordination among
      countries on waterbird management has little precedent. Yet intergovernmental
      treaties now mandate the use of sustainable, adaptive harvest strategies, whose
      development is challenged by a paucity of demographic information. In this study,
      we explore how a combination of allometric relationships, fragmentary monitoring
      and research information, and expert judgment can be used to estimate the
      parameters of a theta-logistic population model, which in turn can be used in a
      Markov decision process to derive optimal harvesting strategies. We show how to
      account for considerable parametric uncertainty, as well as for different
      management objectives. We illustrate our methodology with a poorly understood
      population of Taiga Bean Geese (Anser fabalis fabalis), which is a popular game
      bird in Fennoscandia. Our results for Taiga Bean Geese suggest that they may have
      demographic rates similar to other, well-studied species of geese, and our model
      based predictions of population size are consistent with the limited monitoring
      information available. Importantly, we found that by using a Markov decision
      process, a simple scalar population model may be sufficient to guide harvest
      management of this species, even if its demography is age structured. Finally, we
      demonstrated how two different management objectives can lead to very different
      optimal harvesting strategies, and how conflicting objectives may be traded off
      with each other. This approach will have broad application for European
      waterbirds by providing preliminary estimates of key demographic parameters, by
      providing insights into the monitoring and research activities needed to
      corroborate those estimates, and by producing harvest management strategies that
      are optimal with respect to the managers' objectives, options, and available
      demographic information.

PMID- 29205645
TI  - Using ricelands to provide temporary shorebird habitat during migration.
AB  - To help mitigate large wetland losses in California, The Nature Conservancy
      launched a dynamic conservation incentive program to create temporary wetland
      habitats in harvested and fallow rice fields for shorebirds migrating along the
      Pacific Flyway. Farmers were invited to participate in a reverse auction bidding
      process and winning bids were selected based on their cost and potential to
      provide high quality shorebird habitat. This was done in 2014 and 2015, for
      separate enrollment periods that overlapped with spring and fall migration, both
      before and after the traditional post-harvest flooding period. To assess the
      success of the program, we monitored shorebird use of fields that were enrolled
      (treatments), and others that were subject to typical rice farm management
      (controls). To put these observations in context, we used satellites to
      simultaneously monitor the extent of shallow-water habitat across the ~215,000 ha
      of ricelands in the area. Results showed that providing habitat during migration,
      when it is typically unavailable in rice fields, yielded the largest average
      shorebird densities ever reported for agriculture in the region. Treatment fields
      had significantly greater shorebird density, richness and diversity than control
      fields in both spring and fall (especially September-early October, and late
      March-early April), but in fall the difference was greater. Shorebird responses
      to habitat provisioning, and regional habitat conditions, were variable from year
      to year, and highly dynamic within a given season. Overall, shorebirds densities
      were found to be negatively related to the total amount of flooded habitat in the
      rice landscape. Factors that affected habitat availability included allocation
      schedules of water deliveries from reservoirs, and rainfall patterns, both of
      which were influenced by drought. Collectively, these results suggest that
      appropriately managed agricultural lands have great potential to provide high
      value habitat for shorebirds during times of habitat deficit, including
      migration, and that fall may be a particularly impactful time to create
      additional habitat. Migratory species face great challenges due to the climate
      change, conversion of historical stopover sites, and other factors, but dynamic
      conservation programs offer promise that, at least in certain instances, their
      needs can still be met.

PMID- 29205646
TI  - Infantile Pompe Disease and Enzyme Replacement Therapy.

PMID- 29205647
TI  - Beyond the bedside.

PMID- 29205648
TI  - Therapeutic Options to Improve Bone Health Outcomes in Duchenne Muscular
      Dystrophy: Zoledronic Acid and Pubertal Induction.

PMID- 29205649
TI  - Progressive bull's-eye lesions in the skin of a healthy child.

PMID- 29205650
TI  - Progressive bull's-eye lesions in the skin of a healthy child.

PMID- 29205652
TI  - When best interests are not good enough.

PMID- 29205651
TI  - Gut microbiota in early life and its influence on health and disease: A position
      paper by the Malaysian Working Group on Gastrointestinal Health.
AB  - The role of gut microbiota in early life and its impact on gut health and
      subsequent diseases remain unclear. There is a lack of research and awareness in
      this area, especially in the Asia-Pacific region, including Malaysia. This paper
      reports the position of a Malaysian Working Group on some key issues surrounding
      gut microbiota in early life and its role in gut health and diseases, as well as
      experts' stand on probiotics and prebiotics. The group reached a consensus that
      certain factors, including elective caesarean; premature deliveries;
      complementary feeding; use of antibiotics, prebiotics and/or probiotics; and
      exposure to the external environmental, have an impact on gut microbiota in early
      life. However, as evidence is lacking, especially from the Asia-Pacific region,
      further studies are needed to understand how gut microbiota in early life affects
      subsequent diseases, including allergy, inflammatory bowel disease, obesity and
      infantile colic. Lastly, although beneficial in acute diarrhoeal disease and
      probably allergic eczema, probiotics (and/or prebiotics) should be used
      cautiously in other gut dysbiotic conditions until more data are available.

PMID- 29205653
TI  - Expanded Newborn Screening Programme in Saudi Arabia: Are We Ready?

PMID- 29205654
TI  - Strategies for treatment of pre-schoolers with episodic viral wheeze.

PMID- 29205655
TI  - Short Sleep Duration and Obesity Among Children.

PMID- 29205656
TI  - Another Look at Hereditary Partial Androgen Insensitivity Syndrome in an
      Indigenous Community in the Northern Territory of Australia.

PMID- 29205657
TI  - Outcome for 22-24 week gestation newborns.

PMID- 29205659
TI  - Role of montelukast in management of episodic viral wheeze.

PMID- 29205658
TI  - Late Dumping Syndrome in a 17-Year-Old Female With Charge Syndrome.

PMID- 29205661
TI  - Child with asymptomatic yellow-orange plaques on the frontal region.

PMID- 29205660
TI  - Child with asymptomatic yellow-orange plaques on the frontal region.

PMID- 29205663
TI  - Egg allergy prevention.

PMID- 29205662
TI  - Prophylactic Vitamin D Supplementation in High-Risk Breastfed Infants.

PMID- 29205664
TI  - Disease marketing.

PMID- 29205665
TI  - Toxicity of docetaxel, carboplatin, and trastuzumab combination as adjuvant or
      neo-adjuvant treatment for Her2 positive breast cancer patients and impact of
      colony-stimulating factor prophylaxis.
AB  - While the docetaxel, carboplatin, and trastuzumab (TCH) regimen is one of the
      standard treatments in Her2-positive breast cancer, however, acute toxicities,
      especially those related to the high rate of neutropenia are consistently
      reported. Primary: To compare the toxicity of TCH in current clinical practice vs
      the toxicity observed in the pivotal study, comparing the toxicity in patients
      that received primary prophylaxis (PP) with colony-stimulating factors vs those
      that did not receive PP. Secondary: To describe the demographic and clinical
      characteristics of the study sample, as well as the adverse effects and survival.
      The data regarding 95 patients were analyzed. Observed toxicity (hematological
      and extra-hematological) was greater compared to the pivotal study, with the
      exception of neuropathy and neutropenia. Toxicities "PP" vs "no PP": Extra
      hematological grade 3-4 toxicities: Significant reduction was observed in the
      "PP" group vs the "no PP" group referred to fatigue, stomatitis, nausea, and
      vomiting. Hematological grade 3-4 toxicities: Lesser neutropenia, leukopenia, and
      febrile neutropenia were observed in the "PP" group. Complications associated to
      treatment: No grade 3-4 cardiac toxicity, leukemia or deaths were recorded. DFS
      and OS: After a mean follow-up of 22.9 months, only one bone metastatic relapse
      was detected (DFS: 98.9%; OS: 100%). The combination TCH is very active and
      effective as adjuvant and neo-adjuvant therapy in Her2-positive breast cancer,
      and is currently regarded as standard treatment. However, global toxicity as well
      as hematological toxicity is elevated. The incorporation of PP to TCH
      significantly reduces hematological toxicity and some of the global toxicity,
      thus favoring treatment implementation and lessening the clinical complications.
      We therefore recommend generalization of PP with colony-stimulating factors in
      patients receiving TCH.

PMID- 29205666
TI  - Evaluation of 17% EDTA and 10% citric acid in smear layer removal and tubular
      dentin sealer penetration.
AB  - The purpose of this study was to compare the efficacy of different chelating
      solutions (17% EDTA and 10% citric acid) on the smear layer removal, and their
      effect on tubular dentin sealer penetration. Sixty root canals were prepared and
      distributed into four groups (n = 15) according to the final irrigation protocol:
      G1, final irrigation with 2.5 mL of distilled water; G2, final irrigation with
      2.5 mL of 2.5% sodium hypochlorite solution; G3, final irrigation with 2.5 mL of
      17% EDTA; and G4, final irrigation with 2.5 mL of 10% citric acid. Five specimens
      from each group were not filled to assess smear layer removal by scanning
      electron microscopy. Ten specimens from each group were filled for analysis of
      sealer penetration into dentinal tubules by confocal laser scanning microscopy.
      Smear layer removal (Kruskal-Wallis and Dunn's tests) and sealer penetration (F
      and Tukey's tests) were statistically analyzed with 95% of significance level. G3
      and G4 had greater smear layer removal rates in the cervical and middle thirds,
      in comparison with G1 and G2 (p < .05). G3 and G4 had the highest percentages of
      sealer penetration in all thirds, in comparison with G1 and G2 (p < .05). Smear
      layer removal was effective only at the cervical and middle thirds when the
      chelating solutions were used. Sealer penetration into the dentinal tubules
      significantly increased in all root thirds when the specimens were treated with
      both chelating solutions.

PMID- 29205667
TI  - The effect of postnatal manganese exposure on the NMDA receptor signaling pathway
      in rat hippocampus.
AB  - Overexposure to manganese (Mn) is associated with neurological disorders in
      children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling
      pathway was critical for neurobehavioral function. However, whether NMDA receptor
      signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In
      this study, newborn Sprague-Dawley rats were randomly assigned to four groups
      exposed to 0, 10, 20, and 30 mg/kg of Mn2+ by intraperitoneal injection (n =
      10/group: five males and five females). After 3 weeks of Mn exposure, messenger
      RNA (mRNA) and protein expression of NMDA receptor subunits (NR1, NR2A, and
      NR2B), cAMP-response element binding protein (CREB), and brain-derived
      neurotrophic factor (BDNF) in hippocampus were measured by real-time quantitative
      RT-PCR and Western blot. In Mn-exposed rats, decreased mRNA and protein
      expression of NR1, NR2A, and NR2B, CREB, and BDNF was observed. The results imply
      that downregulated NMDA receptor signaling pathway may be of vital importance in
      the neuropathological process of Mn-induced neurotoxicity.

PMID- 29205668
TI  - Cerebrovascular blood pressure autoregulation monitoring and postoperative
      transient ischemic attack in pediatric moyamoya vasculopathy.
AB  - BACKGROUND: Children with moyamoya vasculopathy are at high risk of perioperative
      cerebral ischemia or hyperperfusion. Maintaining blood pressure within the range
      of functional cerebrovascular blood pressure autoregulation might reduce the risk
      of perioperative neurologic injury. AIMS: We tested whether blood pressure
      autoregulation is associated with postoperative transient ischemic attack in a
      study of patients with pediatric moyamoya vasculopathy. METHODS: We conducted an
      observational study of 15 pediatric patients undergoing surgical
      revascularization with pial synangiosis. Nine patients had bilateral moyamoya and
      6 had unilateral moyamoya. We measured autoregulatory vasoreactivity
      intraoperatively and during the first postoperative night with the hemoglobin
      volume index, a value derived from near-infrared spectroscopy. We also identified
      the optimal mean arterial blood pressure at which autoregulation was most robust
      in each patient. RESULTS: Of the 15 children monitored, 3 with bilateral moyamoya
      and one with unilateral moyamoya experienced a transient ischemic attack. Poorer
      autoregulation during surgery was associated with postoperative transient
      ischemic attack among those with bilateral vasculopathy (P = .048, difference in
      hemoglobin volume index medians: 0.023, 95% confidence interval: 0.003-0.071).
      This relationship was not observed with postoperative autoregulation. The optimal
      mean arterial blood pressure was identifiable during surgery in all monitored
      patients, varied among patients, and often differed between the intraoperative
      and postoperative periods. CONCLUSION: Dysfunctional intraoperative
      autoregulation may increase the risk of TIA in patients with pediatric moyamoya
      vasculopathy. The blood pressure range that supports autoregulation appears to
      vary among patients. Using autoregulation monitoring to guide individualized
      blood pressure goals should be studied as a potential method to reduce
      perioperative neurologic morbidity in pediatric patients with moyamoya.

PMID- 29205669
TI  - Prospective analysis of serious cardiorespiratory events in children during
      ophthalmic artery chemotherapy for retinoblastoma under a deep standardized
      anesthesia.
AB  - BACKGROUND AND OBJECTIVE: Serious adverse cardiorespiratory events complicate
      super selective ophthalmic artery chemotherapy for retinoblastoma in anesthetized
      children. Their mechanism remains unclear but may be attributed to an autonomic
      nervous reflex induced by the catheter close to the ophthalmic artery. Inadequate
      depth of anesthesia during catheter stimulation might be an aggravating factor.
      Thus, we tested whether deep general anesthesia reduced the incidence of serious
      cardiorespiratory events. METHODS: Children were prospectively included in this
      observational study. Standardized deep general anesthesia with sevoflurane,
      rocuronium, and sufentanil was administered. Sevoflurane MAC was kept between 1.5
      and 1.7 and additional sufentanil administered. Serious cardiorespiratory event
      criteria were predefined and included arterial hypotension, bradycardia, and
      severe decrease in lung compliance. They were recorded and the factors
      influencing their occurrence were investigated. RESULTS: One hundred fifteen
      procedures were performed on 32 children. The median MAC of sevoflurane was 1.5
      and median BIS value was 44. Serious cardiorespiratory events occurred in 20% of
      procedures and were mainly severe decrease in lung compliance (83% of events).
      All of them required active treatment. One procedure was aborted due to
      cardiorespiratory compromise and required an epinephrine infusion. All severe
      decreases in lung compliance occurred within 2 minutes after catheter insertion
      in the ophthalmic artery. No recorded demographic and endovascular
      characteristics were associated with serious cardiorespiratory events.
      CONCLUSION: Serious cardiorespiratory events occur commonly during super
      selective ophthalmic artery chemotherapy. Standardized deep anesthesia with
      analgesia did not appear to be protective. No predictive factors were identified,
      but these events systematically arose within 2 minutes after ophthalmic artery
      catheter insertion. Anesthetists and neuroradiologists should be prepared to
      manage these serious complications and parents should be informed of the risks.

PMID- 29205670
TI  - Neck Vessel Cross-Sectional Area Measured with MRI: Scan-Rescan Reproducibility
      for Longitudinal Evaluations.
AB  - BACKGROUND AND PURPOSE: The cross-sectional area (CSA) of common carotid arteries
      internal carotid arteries (CCA-ICAs), vertebral arteries (VAs), and internal
      jugular veins (IJVs) is influenced by aging. However, the neck vessel CSA can be
      affected by other factors as well, including subject positioning, hydration, and
      respiration, especially in longitudinal studies. This study aimed to assess scan
      rescan reproducibility of CCA-ICAs, VAs, and IJVs CSA measurements in order to
      evaluate their feasibility for longitudinal CSA assessments, and to apply the
      segmentation method on a longitudinal pilot dataset. METHODS: Two set of 2
      dimensional neck magnetic resonance angiography (MRA) images were acquired on a 3
      T scanner from two separate datasets: 9 healthy individuals (HIs) were scanned 5
      days apart (scan-rescan dataset) and 12 HIs were acquired 5 years apart (baseline
      follow-up dataset). CCA-ICAs, VAs, and IJVs were segmented along the whole vessel
      length between C3 and C7 intervertebral spaces. Repeated measure analysis of
      covariance, adjusted for cervical level and sample, and Wilcoxon signed-rank sum
      test were used to assess the scan-rescan and baseline-follow-up CSA differences.
      Intraclass correlation coefficient (ICC) was also computed to evaluate scan
      rescan reliability. RESULTS: No significant CSA differences were found for the
      scan-rescan and baseline-follow-up CSA comparisons, using the whole vessel length
      or single cervical level measurements. ICC analysis showed good degree of scan
      rescan reproducibility (considering whole vessel measures: ICC > .9, P-value <
      .001 for CCA-ICAs, ICC > .6, P-value < .001 for VAs, and ICC > .7, P-value < .001
      for IJVs). CONCLUSIONS: Scan-rescan reproducibility of CCA-ICAs, VAs, and IJVs
      CSA measurements is high, making longitudinal studies feasible.

PMID- 29205671
TI  - Fronto-parietal coding of goal-directed actions performed by artificial agents.
AB  - With advances in technology, artificial agents such as humanoid robots will soon
      become a part of our daily lives. For safe and intuitive collaboration, it is
      important to understand the goals behind their motor actions. In humans, this
      process is mediated by changes in activity in fronto-parietal brain areas. The
      extent to which these areas are activated when observing artificial agents
      indicates the naturalness and easiness of interaction. Previous studies indicated
      that fronto-parietal activity does not depend on whether the agent is human or
      artificial. However, it is unknown whether this activity is modulated by
      observing grasping (self-related action) and pointing actions (other-related
      action) performed by an artificial agent depending on the action goal. Therefore,
      we designed an experiment in which subjects observed human and artificial agents
      perform pointing and grasping actions aimed at two different object categories
      suggesting different goals. We found a signal increase in the bilateral inferior
      parietal lobule and the premotor cortex when tool versus food items were pointed
      to or grasped by both agents, probably reflecting the association of hand actions
      with the functional use of tools. Our results show that goal attribution engages
      the fronto-parietal network not only for observing a human but also a robotic
      agent for both self-related and social actions. The debriefing after the
      experiment has shown that actions of human-like artificial agents can be
      perceived as being goal-directed. Therefore, humans will be able to interact with
      service robots intuitively in various domains such as education, healthcare,
      public service, and entertainment.

PMID- 29205672
TI  - Repetitive-incessant electrical storm triggered by early repolarization.
AB  - Early repolarization syndrome (ERS) was originally considered a normal variant
      with benign outcome. However, recent studies have demonstrated that it can be
      linked to a considerable risk of life-threatening arrhythmias and sudden cardiac
      death. We report a case with an extraordinary, extremely malignant clinical
      expression of ERS refractory to all antiarrhythmic drugs including quinidine.
      This case demonstrates real-time changes of dynamic electrocardiogram (ECG)
      preceding a polymorphic ventricular tachycardia (VT)-ventricular fibrillation
      (VF) and possible external factors triggering arrhythmia onset. Implantable
      cardioverter-defibrillator (ICD) function was terminated 6 months after
      implantation due to multiple-incessant electrical storm (ES). Catheter ablation
      was the definite treatment of this malignant entity.

PMID- 29205673
TI  - Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism.
AB  - AMP-activated protein kinase (AMPK) is a conserved sensor of cellular energy
      change and is activated by increased AMP/ATP and/or ADP/ATP ratios. AMPK
      maintains the energy balance by decreasing the ATP-consuming processes such as
      transcription of synthetic fat genes and rRNA, the translation of ribosomal
      proteins, synthesis of cholesterol and fatty acid, while the metabolic pathways
      such as glucose and fatty transport, fatty acid oxidation, autophagy,
      mitochondrial synthesis and oxidative metabolism are increased to preserve ATP
      during energy deficiency. Recent advance has demonstrated that AMPK activity has
      a close association with the initiation and progression in various cancers. Here
      we review the mechanisms that AMPK controls energy metabolism through regulating
      ATP synthesis and consumption, and further discuss the deregulation of AMPK in
      cancers.

PMID- 29205674
TI  - Free light chain-associated Fanconi syndrome in an adolescent.

PMID- 29205675
TI  - Exploring associations between psychiatric disorder, psychological distress, and
      health care utilization in cancer patients.
AB  - OBJECTIVE: The mental burden of cancer might elicit additional health care
      utilization. However, it is unclear how psychiatric disorder and psychological
      distress relate to health care utilization. Therefore, this study explores
      associations between psychiatric disorder, psychological distress, and health
      care utilization. It was hypothesized that presence of psychiatric disorder and
      psychological distress was associated with increased health care utilization and
      costs. METHODS: The current study consisted of secondary analyses of baseline
      data of a larger randomized controlled trial. Two hundred forty-five mixed-cancer
      patients with at least mild symptoms of psychological distress (Hospital Anxiety
      and Depression Scale-T >= 11) were mainly recruited via online media,
      participating centers and patient associations. Patients were assessed with
      Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I) for
      depressive, anxiety, and/or adjustment disorder. Psychological distress was
      measured by the Hospital Anxiety and Depression Scale. Retrospective self
      reported health care utilization in the past 3 months was collected. Associations
      between predictors and health care utilization in terms of incidence rate ratios
      (IRR) and costs per category (mental, primary, somatic, and complementary) were
      assessed by negative binomial, logistic, and gamma regression. RESULTS: Eighty
      nine (36.3%) patients suffered from psychiatric disorder, which was associated
      with mental health care utilization (IRR = 1.63) and costs (OR = 3.11). We
      observed a nonsignificant trend of somatic health care utilization in patients
      with psychiatric disorder. Psychological distress was associated with mental
      health care utilization (IRR = 1.09) and costs (OR = 1.09). Psychological
      distress was also associated with complementary health care utilization (IRR =
      1.03). CONCLUSION: Psychiatric disorder and psychological distress were
      associated with mental health care use and costs. Psychological distress was
      associated with complementary health care use. Adequate assessment and referral
      to mental health care might prevent unnecessary health care utilization.

PMID- 29205676
TI  - Now more than ever.

PMID- 29205678
TI  - Perioperative management of gastrostomy tube placement in Duchenne muscular
      dystrophy adolescent and young adult patients: A role for a perioperative
      surgical home.
AB  - BACKGROUND: In past decades, Duchenne muscular dystrophy patients have been
      living longer and as the disease advances, patients experience multisystemic
      deterioration. Older patients often require gastrostomy tube placement for
      nutritional support. For optimizing the perioperative care, a practice of
      multidisciplinary team can better anticipate, prevent, and manage possible
      complications and reduce the overall perioperative morbidity and mortality. AIMS:
      The aim of this study was to review our experience with perioperative care of
      adolescent and young adults with Duchenne muscular dystrophy undergoing
      gastrostomy by various surgical approaches in order to identify challenges and
      improve future perioperative care coordination to reduce morbidity. METHODS: We
      retrospectively examined cases of gastrostomy tube placement in patients of ages
      15 years and older between 2005 and 2016. We reviewed preoperative evaluation,
      anesthetic and surgical management, and postoperative complications. RESULTS:
      Twelve patients were identified; 1 had open gastrostomy, 3 laparoscopic
      gastrostomies, 5 percutaneous endoscopic guided, and 3 radiologically inserted
      gastrostomy tubes. All patients had preoperative cardiac evaluation with 6
      patients demonstrating cardiomyopathy. Nine patients had preoperative pulmonary
      consultations and the pulmonary function tests reported forced vital capacity of
      <=36% of predicted. Eight patients were noninvasive positive pressure ventilation
      dependent. General anesthesia with tracheal intubation was administered in 8
      patients, and intravenous sedation in 4 patients; 1 received sedation
      supplemented with regional anesthesia and 3 received deep sedation. One patient
      had a difficult intubation that resulted in trauma and prolonged tracheal
      intubation. Three patients developed postoperative respiratory complications. Two
      patients' procedures were postponed due to inadequate preoperative evaluation and
      1 because of disagreement between anesthesia and procedural services as to the
      optimal approach for airway management. CONCULSION: Optimal management of the
      perioperative care of Duchenne muscular dystrophy patients requires input from
      relevant medical specialists, proceduralist and anesthesiologist. This complexity
      of care coordination presents an opportunity for anesthesiologists to lead a
      collaborative perioperative team in management of advanced Duchenne patients
      coming for gastrostomy.

PMID- 29205681
TI  - Meroistic oogenesis of Drosophila, in section in situ.

PMID- 29205679
TI  - Prevalence and characteristics of human parechovirus and enterovirus infection in
      febrile infants.
AB  - BACKGROUND: Human parechovirus (HPeV) and human non-polio enterovirus (EV) are
      important causes of fever without source (FWS) in young infants. Their prevalence
      and clinical characteristics are largely unknown in Asian countries. This study
      was conducted to elucidate the epidemiology and clinical characteristics of HPeV
      and EV infection in febrile young infants in Japan. METHODS: During February 2010
      August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal fluid
      samples from 56 infants (<3 months) with FWS at a single hospital. To each
      sample, we applied reverse transcription-polymerase chain reaction for HPeV and
      EV. We compared the clinical characteristics of HPeV and EV patients. RESULTS:
      HPeV was detected in 11 and EV in 17 patients. HPeV was detected during July
      September. HPeV patients, compared with EV patients, had lower age (32 vs 47
      days; P = n.s.), higher prevalence of exclusive breast-feeding (81.8 vs 29.4%; P
      = 0.024), and lower prevalence of sick contacts (36.4 vs 88.2%; P = 0.010). More
      HPeV than EV patients met the systemic inflammatory response syndrome criteria
      (90.9 vs 52.9%; P = 0.049). In the HPeV group, leukopenia, thrombopenia, and
      elevated deviation enzyme were observed, although the prevalence of abnormal
      cerebrospinal fluid was significantly lower than in the EV group. HPeV patients
      had longer hospital stay (7 vs 5 days; P = 0.025). CONCLUSION: HPeV and EV are
      important causal viruses of FWS. Characteristic clinical pictures exist in these
      virus infections, but further research is needed to accumulate more cases to
      produce a comprehensive picture of these virus infections.

PMID- 29205682
TI  - Sibling visits and viral infection in the neonatal intensive care unit.
AB  - BACKGROUND: Sibling visits to the neonatal intensive care unit (NICU) are a part
      of family-centered care, which is now being increasingly endorsed as a positive
      development in patient care. Sibling visits, however, pose a risk of viral
      infection, and hence many NICU in Japan impose strict limits on the practice. The
      aim of this study was therefore to assess whether sibling visits to the NICU are
      related to an increase in the nosocomial viral infection rate. METHODS: This
      retrospective study was conducted between April 2012 and March 2017 at Tokyo
      Metropolitan Children's Medical Center in Japan. Sibling visits were implemented
      after screening for symptoms of viral illness. Symptomatic patients in the NICU
      were tested for common viruses on rapid antigen test and polymerase chain
      reaction. The number of sibling visits and the rate of nosocomial viral
      infections were examined on Spearman's correlation test. RESULTS: The total
      number of sibling visits and rate of nosocomial viral infection in the NICU was
      102 and 0.068 per 1,000 patient-days during the study period, respectively. The
      number of enterovirus, respiratory syncytial virus, human metapneumovirus,
      influenza virus A, and Herpes simplex virus infections was 3, 2, 1, 1, 1, and 1,
      respectively. No infections were identified after sibling visits. The number of
      sibling visits and the rate of nosocomial viral infections were not correlated
      (correlation coefficient, -0.1; P = 0.873). CONCLUSION: Sibling visits to the
      NICU did not result in an increase in the nosocomial viral infection rate.

PMID- 29205683
TI  - Corrigendum.

PMID- 29205684
TI  - Erratum.

PMID- 29205685
TI  - A peek into epidemiology, screening, management of breast cancer in developing
      countries: Experience from two regional cancer centers in India.

PMID- 29205686
TI  - Ultrasound-guided lower forearm median nerve block in open surgery for trigger
      thumb in 1- to 3-year-old children: A randomized trial.
AB  - BACKGROUND AND AIM: Trigger thumb is a common hand disability in children and is
      primarily treated with open surgery. A conscious median nerve block can usually
      meet the requirements for trigger thumb-releasing surgery in adults; however, its
      effectiveness in children requires further clarification. The present study aims
      to demonstrate whether ultrasound-guided lower forearm median nerve blockade is a
      viable option for children undergoing open surgery for trigger thumb. METHODS: A
      prospective randomized study was designed to compare median nerve blocks guided
      by ultrasonography with those guided by anatomic landmarks. Following induction
      of general anesthesia, the children received a median nerve block performed
      either by ultrasound-guided block of the lower forearm (group U) or landmark
      based blocking at the proximal wrist crease level (group T) with a 0.2%
      ropivacaine injection. The success rates were compared between groups as the
      primary endpoint; additional sufentanil and propofol administration, anesthesia
      recovery time, and other secondary endpoints were also compared. RESULTS: A total
      of 100 children (age 1-3 years) with ASA status I who were scheduled for open
      surgery for trigger thumb were included in this study (n = 50 per group). Thirty
      seven children in group T and 50 children in group U underwent successful blocks.
      The rate of unsuccessful blockade was significantly lower in group U than group T
      (0% and 26%, respectively), and rate of additional sufentanil and propofol
      administration was also lower in group U than in group T. CONCLUSION: Ultrasound
      guided lower forearm median nerve block can provide more effective analgesia, a
      higher success rate, and lower general and local anesthetic dosages than the
      anatomic landmark-based blocking method in children undergoing open surgery for
      trigger thumb.

PMID- 29205687
TI  - Ultrasound-guided pudendal nerve block in children: A new technique of ultrasound
      guided transperineal approach.
AB  - BACKGROUND: Transperineal pudendal nerve block guided by nerve stimulator is used
      in pediatric anesthesia as an alternative to caudal analgesia in perineal
      surgery. The risk of rectal puncture or intravascular injection is inherent to
      this blinded technique. We described a new technique of transperineal pudendal
      nerve block, with ultrasound guidance, to improve safety of the technique. AIMS:
      The first goal of this study was to describe this new technique and to test its
      feasibility. The second objective was to evaluate intra operative effectiveness
      and postoperative pain control. METHODS: After parental and children consent,
      this prospective descriptive study included children aged 1-15 years, ASA status
      I-III, scheduled for general anesthesia associated with bilateral pudendal nerve
      block for an elective perineal surgery. After standardized general anesthesia,
      the anesthesiologist performed pudendal nerve block under ultrasound guidance
      with "out of plane" approach and evaluated the visualization of anatomical
      structures (ischial tuberosity, rectum, and pudendal artery), of the needle and
      of the local anesthetic spread. Pudendal nerve block failure was defined as an
      increase in mean arterial blood pressure or heart rate more than 20% compared to
      baseline values after surgical incision. In the postoperative period, the need
      for rescue analgesia was noted. RESULTS: During the study period, 120 blocks were
      performed in 60 patients, including 59 boys. Quality of the ultrasonographic
      image was good in 81% of blocks, with easy visualization of ischium and rectum in
      more than 95% of cases. Localization of the tip of the needle was possible for
      all pudendal nerve blocks, directly or indirectly. The spread of local anesthetic
      was seen in 79% of cases. The block was effective in 88% of cases. CONCLUSION:
      The new technique of ultrasound-guided pudendal nerve block, described in this
      study, seems to be easy to perform with a good success rate, and probably
      improves safety of the puncture and of the injection by real-time visualization
      of anatomical structures and local anesthetic spread.

PMID- 29205688
TI  - Integration of radiology and clinical score in pediatric appendicitis.
AB  - BACKGROUND: The efficacy of ultrasonography (US) and abdominal X-ray in
      combination with Pediatric Appendicitis Score (PAS) is complicated in the
      diagnosis of acute appendicitis. Abdominal X-ray is as useful as US with clinical
      assessment when evaluated by experienced pediatric radiologist in acute
      appendicitis. The aim of this study was to determine the value of US and
      abdominal X-ray for appendicitis in children when combined with clinical
      assessment based on PAS, and to establish a practical pathway for acute
      appendicitis in childhood. METHODS: A prospective, observational cohort study was
      conducted at an urban, academic pediatric emergency department. Patients were
      classified at low (PAS 1-4), intermediate (PAS 5-7), or high (PAS 8-10) risk for
      appendicitis. Low-risk patients were discharged with telephone follow-up in <=10
      days; those at intermediate risk underwent X-ray and US. High-risk patients
      received immediate surgical consultation. Patients were grouped on histopathology
      as having either proven acute appendicitis or no appendicitis. RESULTS: A total
      of 288 children were analyzed. Surgery was performed in 134 patients (46.5%), and
      128 (95.5%) had positive histopathology. Mean PAS in the patients with and
      without appendicitis was 7.09 +/- 1.42 and 4.97 +/- 2.29, respectively (P =
      0.00). The rate of missed cases was 6/288 (2%), and the negative appendectomy
      rate was 6/134 (4.4%). When the score cut-off was set at 6, the sensitivity and
      specificity of PAS was 86.7% and 63.1%, respectively. The diagnostic performance
      of daytime US had a sensitivity of 91.1% and specificity of 71.1%. Also, positive
      US or PAS >6 or both, had sensitivity and specificity 96.7% and 59.9%,
      respectively. CONCLUSION: US or abdominal X-ray in children with possible
      appendicitis should be integrated with PAS to determine the next steps in
      management. In the case of discordance between the clinical findings and
      radiology, prolonged observation or further imaging are recommended.

PMID- 29205689
TI  - Ultrasound findings and associated factors to morbidity in Schistosoma
      haematobium infection in a highly endemic setting.
AB  - OBJECTIVE: To evaluate the usefulness of the WHO classification of ultrasound
      pathological changes and to establish risk factors for morbidity in a highly
      endemic setting. METHODS: One hundred and fifty-seven ultrasounds were performed
      on school-aged children previously diagnosed with urinary schistosomiasis in
      Cubal, Angola. The findings were analysed according to the WHO guidelines.
      Factors for morbidity were studied. RESULTS: Mean age of the children was 8.7 (SD
      3.2) years. Pathological changes were found in 85.3% (84.7% in the bladder, 34.4%
      the ureter and 6.3% kidney lesions). The global score according to the WHO
      classification was 5.74. Male gender [OR 2.61 (1.04-6.58); P 0.043] and older age
      [OR 2.96 (1.17-7.46); P 0.023] were associated with a higher risk of developing
      any kind of urinary abnormality. Proteinuria was present in 61.7% of the
      children. Macroscopic haematuria [OR 2.48 (1.11-5.58); P = 0.02)] and a high
      level of proteinuria > 300 mg/dl [OR 5.70 (2.17-14.94); P 300 mg/dl)] were
      associated with abnormalities of the upper urinary tract and showed good positive
      and negative predictive values for the detection of pathology in the upper
      urinary tract (65.5% and 71.1%, respectively). CONCLUSIONS: Severe urinary tract
      pathology was found in a high percentage of the children in our setting.
      Microhaematuria and proteinuria were good markers of morbidity, proteinuria being
      more precise for severe alterations of the upper urinary tract. We suggest
      initial and evolutive ultrasound in children diagnosed with schistosomiasis, and
      close monitoring including periodic controls. As schistosomiasis control efforts
      are currently focused on reducing morbidity, tests that detect the presence or
      degree of morbidity are essential for targeting treatment and tracking the
      progress of control campaigns.

PMID- 29205690
TI  - Refinement of detecting atrial fibrillation in stroke patients: results from the
      TRACK-AF Study.
AB  - BACKGROUND AND PURPOSE: Detection of occult atrial fibrillation (AF) is crucial
      for optimal secondary prevention in stroke patients. The AF detection rate was
      determined by implantable cardiac monitor (ICM) and compared to the prediction
      rate of the probability of incident AF by software based analysis of a
      continuously monitored electrocardiogram at follow-up (stroke risk analysis,
      SRA); an optimized AF detection algorithm is proposed by combining both tools.
      METHODS: In a monocentric prospective study 105 out of 389 patients with
      cryptogenic stroke despite extensive diagnostic workup were investigated with two
      additional cardiac monitoring tools: (a) 20 months' monitoring by ICM and (b) SRA
      during hospitalization at the stroke unit. RESULTS: The detection rate of occult
      AF was 18% by ICM (n = 19) (range 6-575 days) and 62% (n = 65) had an increased
      risk for AF predicted by SRA. When comparing the predictive accuracy of SRA to
      ICM, the sensitivity was 95%, specificity 35%, positive predictive value 27% and
      negative predictive value 96%. In 18 patients with AF detected by ICM, SRA also
      showed a medium risk for AF. Only one patient with a very low risk predicted by
      SRA developed AF revealed by ICM after 417 days. CONCLUSIONS: A combination of
      SRA and ICM is a promising strategy to detect occult AF. SRA is reliable in
      predicting incident AF with a high negative predictive value. Thus, SRA may serve
      as a cost-effective pre-selection tool identifying patients at risk for AF who
      may benefit from further cardiac monitoring by ICM.

PMID- 29205691
TI  - Intravenous immunoglobulin in drug and device refractory patients with the
      symptoms of gastroparesis-an open-label study.
AB  - BACKGROUND: Gastroparesis is a complex clinical entity; many aspects of which
      remain unknown. Although most patients have idiopathic, diabetic, or postsurgical
      gastroparesis, many are thought to have measurable neuromuscular abnormalities.
      Immunotherapy has recently been utilized to treat suspected autoimmune
      gastrointestinal dysmotility. METHODS: Fourteen patients with symptoms of
      gastroparesis (Gp) who were refractory to drug/device were selected from 443 Gp
      patients from 2013 to 2015 who were treated at the University of Louisville
      motility center. All patients underwent a structural and psychiatric evaluation
      along with detailed psychological and behavioral examination to rule out eating
      disorders. We performed detailed neuromuscular evaluation and all 14 patients
      received at least 12 weeks of intravenous immunoglobulin (400 mg/kg infusion
      weekly). Response was defined subjectively (symptomatic improvement) using
      standardized IDIOM score system. KEY RESULTS: All 14 patients had serological
      evidence and/or tissue evidence of immunological abnormality. Post-IVIG therapy,
      there was a significant improvement in symptoms scores for nausea, vomiting,
      early satiety, and abdominal pain. CONCLUSIONS AND INFERENCES: Although limited
      by the absence of placebo group, the data illustrate the role of autoimmunity and
      neuromuscular evaluation in patients with gastroparesis and support the utility
      of a diagnostic trial of immunotherapy in an effort to improve therapeutic
      outcomes for such patients.

PMID- 29205692
TI  - Changing brain connectivity dynamics: From early childhood to adulthood.
AB  - Brain maturation through adolescence has been the topic of recent studies.
      Previous works have evaluated changes in morphometry and also changes in
      functional connectivity. However, most resting-state fMRI studies have focused on
      static connectivity. Here we examine the relationship between age/maturity and
      the dynamics of brain functional connectivity. Utilizing a resting fMRI dataset
      comprised 421 subjects ages 3-22 from the PING study, we first performed group
      ICA to extract independent components and their time courses. Next, dynamic
      functional network connectivity (dFNC) was calculated via a sliding window
      followed by clustering of connectivity patterns into 5 states. Finally, we
      evaluated the relationship between age and the amount of time each participant
      spent in each state as well as the transitions among different states. Results
      showed that older participants tend to spend more time in states which reflect
      overall stronger connectivity patterns throughout the brain. In addition, the
      relationship between age and state transition is symmetric. This can mean
      individuals change functional connectivity through time within a specific set of
      states. On the whole, results indicated that dynamic functional connectivity is
      an important factor to consider when examining brain development across
      childhood.

PMID- 29205694
TI  - Fetal sex discordance in a monochorionic twin pregnancy following
      intracytoplasmic sperm injection: A case report of chimerism and review of the
      literature.
AB  - A 39-year-old woman who became pregnant with twins after an intracytoplasmic
      sperm injection was referred at the ninth gestational week to determine
      chorionicity. Ultrasonographic examination showed a monochorionic diamniotic twin
      pregnancy. First trimester nuchal translucency measurements of the fetuses were
      1.6 and 2.7 mm. A non-invasive prenatal test was performed and revealed low risk.
      One fetus appeared to be female and the other male at the 14th gestational week.
      Second trimester anatomic scanning results were otherwise normal for both
      fetuses. The newborns delivered at term appeared to be normal female and male
      babies phenotypically. At the fourth month, buccal cell analysis showed chimeric
      karyotypes, 46,XX[98]/46,XY[2] and 46,XY[98]/46,XX[2] in the female and male
      infant, respectively. The recognition of sex discordance despite monochorionicity
      may be a clue for the diagnosis of such rare cases of chimerism in dizygotic
      twins, most of which occur in pregnancies obtained by assisted reproductive
      technology.

PMID- 29205693
TI  - Evaluation of factors related to glycaemic control among South Korean patients
      with type 2 diabetes.
AB  - AIMS: To examine specific self-care behaviours, depression, and diabetes-related
      stress among South Korean patients with type 2 diabetes and to evaluate whether
      these factors are related to glycaemic control. METHODS: This cross-sectional
      study included 171 patients with type 2 diabetes who visited an endocrinology
      clinic. A structured questionnaire and electronic medical records were used to
      collect data regarding self-care behaviours, depression, diabetes-related
      distress, and glycaemic control between May 2015 and July 2015. RESULTS: Compared
      with the group with good glycaemic control, the group with poor glycaemic control
      had significantly lower values for medication adherence and significantly greater
      values for regimen-related distress. Depression was not significantly associated
      with glycaemic control. In logistic regression analysis, only medication
      adherence was independently associated with glycaemic control. CONCLUSIONS:
      Medication adherence should be continuously emphasized and monitored in clinical
      practice to effectively manage glycaemic control among patients with type 2
      diabetes. Furthermore, consideration of diabetes-related distress may help
      improve glycaemic control among patients with type 2 diabetes.

PMID- 29205696
TI  - Teacher-child relationships and classroom-learning behaviours of children with
      developmental language disorders.
AB  - BACKGROUND: Children with developmental language disorders (DLDs) often struggle
      with classroom behaviour. No study has examined whether positive teacher-child
      relationships may act as a protective factor for children with DLDs in that these
      serve to enhance children's important classroom-learning behaviours. AIMS: To
      examine the association between the quality of teacher-child relationships and
      teacher-rated classroom-learning behaviours of children with DLDs in both
      preschool and kindergarten. METHODS & PROCEDURES: Longitudinal data were
      collected on 191 preschoolers (mean = 42.4 months of age, SD = 11.6 months) with
      DLDs in special education classrooms during preschool and in kindergarten.
      Teacher-child relationship quality was assessed in preschool, and children's
      classroom-learning behaviours were measured in preschool and kindergarten.
      Regression models were used to examine the relationship between teacher-child
      relationship quality and children's concurrent and future classroom-learning
      behaviours. OUTCOMES & RESULTS: Positive teacher-child relationship quality in
      preschool was associated with better classroom-learning behaviours in preschool
      and kindergarten for children with DLDs. Preschool teacher-child relationship
      quality characterized by low levels of conflict and high levels of closeness was
      associated with positive classroom-learning behaviours during preschool. Teacher
      child conflict but not closeness was predictive of children's classroom-learning
      behaviours in kindergarten. CONCLUSIONS & IMPLICATIONS: These results suggest
      that the quality of the teacher-child relationship for children with DLDs during
      preschool is associated within their learning-related behaviours in the classroom
      both concurrently and in the subsequent year. Findings suggest that teacher-child
      relationships should be explored as a mechanism for improving the learning
      related behaviours of children with DLDs.

PMID- 29205695
TI  - Diminished gastric prokinetic response to ghrelin in a rat model of spinal cord
      injury.
AB  - BACKGROUND: Patients with cervical or high-thoracic spinal cord injury (SCI)
      often present reduced gastric emptying and early satiety. Ghrelin provokes
      motility via gastric vagal neurocircuitry and ghrelin receptor agonists offer a
      therapeutic option for gastroparesis. We have previously shown that experimental
      high-thoracic injury (T3-SCI) diminishes sensitivity to another gastrointestinal
      peptide, cholecystokinin. This study tests the hypothesis that T3-SCI impairs the
      vagally mediated response to ghrelin. METHODS: We investigated ghrelin
      sensitivity in control and T3-SCI rats at 3-days or 3-weeks after injury
      utilizing: (i) acute (3-day post-injury) fasting and post-prandial serum levels
      of ghrelin; (ii) in vivo gastric reflex recording following intravenous or
      central brainstem ghrelin; and (iii) in vitro whole cell recording of neurons
      within the dorsal motor nucleus of the vagus (DMV). KEY RESULTS: The 2-day food
      intake of T3-SCI rats was reduced while fasting serum ghrelin levels were higher
      than in controls. Intravenous and fourth ventricle ghrelin increased in vivo
      gastric motility in fasted 3-day control rats but not fasted T3-SCI rats. In
      vitro recording of DMV neurons from 3-day T3-SCI rats were insensitive to
      exogenous ghrelin. For each measure, vagal responses returned after 3-weeks.
      CONCLUSIONS AND INFERENCES: Hypophagia accompanying T3-SCI produces a significant
      and physiologically appropriate elevation in serum ghrelin levels. However,
      higher ghrelin levels did not translate into increased gastric motility in the
      acute stage of T3-SCI. We propose that this may reflect diminished sensitivity of
      peripheral vagal afferents to ghrelin or a reduction in the responsiveness of
      medullary gastric vagal neurocircuitry following T3-SCI.

PMID- 29205697
TI  - Sinter-Resistant Platinum Catalyst Supported by Metal-Organic Framework.
AB  - Single atoms and few-atom clusters of platinum are uniformly installed on the
      zirconia nodes of a metal-organic framework (MOF) NU-1000 via targeted vapor
      phase synthesis. The catalytic Pt clusters, site-isolated by organic linkers, are
      shown to exhibit high catalytic activity for ethylene hydrogenation while
      exhibiting resistance to sintering up to 200  degrees C. In situ IR spectroscopy
      reveals the presence of both single atoms and few-atom clusters that depend upon
      synthesis conditions. Operando X-ray absorption spectroscopy and X-ray pair
      distribution analyses reveal unique changes in chemical bonding environment and
      cluster size stability while on stream. Density functional theory calculations
      elucidate a favorable reaction pathway for ethylene hydrogenation with the novel
      catalyst. These results provide evidence that atomic layer deposition (ALD) in
      MOFs is a versatile approach to the rational synthesis of size-selected clusters,
      including noble metals, on a high surface area support.

PMID- 29205698
TI  - Effects of dietary protein level during rearing period and age at overfeeding on
      magret and foie gras quality in male mule ducks.
AB  - The aim of this trial was to study the effects of dietary protein content during
      the rearing period on the performance of mule ducks, according to age at
      overfeeding (O). Ducks (n = 612) were divided into four groups differing in the
      protein content in the diet offered during the starting period (S, 0-20 days; Sl
      vs. Sh : 150 vs. 175 g/kg crude protein (CP)) and growing-finishing period (GF;
      21-67 or 81 days, depending on age at O; GFl vs. GFh : 133 vs. 152 g/kg CP). The
      relative weight of pectoral muscle was lower when ducks were fed a low protein
      diet during S (-5%, P < 0.01) or GF period (-6%, P < 0.001) at 68 days and higher
      in ducks of the Sl GFh group (+6%; P < 0.05) at 82 days. Both foie gras and
      magret weights fell when ducks were fed Sl or GFl (P < 0.05 and < 0.01).
      Mortality during the O period was higher in ducks fed the Sl diet and overfed at
      late age (7.4% vs. 0%; P < 0.01). In conclusion, a reduction in the dietary
      protein supply should be recommended only during the GF period for ducks overfed
      at a late age.

PMID- 29205699
TI  - Use of telehealth in the delivery of comprehensive care for patients with
      haemophilia and other inherited bleeding disorders.
AB  - Advances in technology such as telemedicine (TM) have made access to cost
      effective, quality health care feasible for remote patients. TM is especially
      well suited for patients with chronic disorders such as haemophilia and related
      haemostatic disorders that benefit not only from more frequent interaction with
      care providers at a specialized haemophilia treatment center but also from
      consultations with other specialists. Telehealth refers to a broader application
      of TM and includes non-clinical services such as education, provider training,
      administrative meetings etc. Collaboration with the local primary care provider
      for management and implementation is key for successful and sustainable TM. This
      review article provides an overview of types of telemedicine, technical aspects,
      its benefits and challenges and focuses on the applicability of this technology
      to persons with bleeding and other blood disorders. Examples of TM strategies,
      process flow of TM clinic and experiences at the authors haemophilia treatment
      center (HTC) setting are shared. In addition, mobile health (mHealth) and
      electronic health (eHealth), both a part of telehealth, and their applications
      are briefly described. Clearly, widespread adoption of this technology will not
      only enhance care of patients but will enable more people, especially in
      underserved areas, to receive specialty care.

PMID- 29205700
TI  - Perineal lipoma with anorectal malformation: Report of two cases and review of
      the literature.

PMID- 29205701
TI  - Antibody response to seasonal influenza vaccination in patients with multiple
      sclerosis receiving immunomodulatory therapy.
AB  - BACKGROUND AND PURPOSE: We have previously shown that patients with multiple
      sclerosis receiving immunomodulatory treatment have reduced seroprotection rates
      after influenza immunization. The aim of this study was to further investigate
      the influence of immunomodulatory therapies on the antibody response and
      seroprotection rates in patients immunized with seasonal influenza vaccine in
      2012/2013 compared with healthy controls. METHODS: Ninety patients receiving
      fingolimod, glatiramer acetate, interferon beta-1a/1b, natalizumab or no therapy
      were compared with 62 healthy controls. All subjects received the inactivated
      split virus vaccine in 2012 and serum samples were collected pre-vaccination and
      3, 6 and 12 months post-vaccination. The vaccine responses were evaluated by the
      hemagglutination inhibition assay and adjusted for age and gender. RESULTS: No
      significant differences in rates of protection against H1N1 for interferon beta
      1a/1b and glatiramer acetate were observed as compared with controls at 3, 6 and
      12 months. Fingolimod provided reduced protection at all time points post
      vaccination, whereas natalizumab displayed reduced protection at 3 and 6 months.
      Patients without immunomodulation did not display protection rates that were
      significantly different from the controls at 3 and 12 months. CONCLUSION: These
      findings suggest that patients with multiple sclerosis receiving fingolimod or
      natalizumab should be considered for a second dose of the vaccine in cases of
      insufficient protection. Our results further indicate that new immunomodulatory
      treatment regimens should be systematically evaluated for their influence on
      influenza-specific vaccine responses.

PMID- 29205702
TI  - Mycobacterium haemophilum osteomyelitis in the immunocompromised host.

PMID- 29205703
TI  - LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting
      miR-193a/MCL1 pathway.
AB  - Although dexamethasone (DEX) remains a first-line agent for multiple myeloma (MM)
      therapy, the development of DEX resistance has become an indicator of poor
      prognosis in MM patients. It is thus urgent to develop strategies to restore the
      vulnerability of MM to DEX. This study demonstrated long non-coding RNA (lncRNA)
      nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX
      resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to
      poor prognosis. The in-depth study revealed that during the development of DEX
      resistance in these cells, the miR-193a levels were decreased, which resulted in
      the increased expression of the target gene myeloid cell leukemia-1 (MCL1). We
      also found knockdown of NEAT1, the DEX-induced sensitivity was enhanced in the
      resistant cells. Meanwhile, overexpression of NEAT1 increased the DEX-induced
      resistance in the sensitive cells. In conclusion, the NEAT1/miR-193a/MCL1 pathway
      is closely associated with the development of DEX resistance in myeloma cells,
      and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.

PMID- 29205705
TI  - Retinal pigment epithelium in the pathogenesis of age-related macular
      degeneration and photobiomodulation as a potential therapy?
AB  - The retinal pigment epithelium (RPE) comprises a monolayer of cells located
      between the neuroretina and the choriocapillaries. The RPE serves several
      important functions in the eye: formation of the blood-retinal barrier,
      protection of the retina from oxidative stress, nutrient delivery and waste
      disposal, ionic homeostasis, phagocytosis of photoreceptor outer segments,
      synthesis and release of growth factors, reisomerization of all-trans-retinal
      during the visual cycle, and establishment of ocular immune privilege. Age
      related macular degeneration (AMD) is the leading cause of blindness in developed
      countries. Dysfunction of the RPE has been associated with the pathogenesis of
      AMD in relation to increased oxidative stress, mitochondrial destabilization and
      complement dysregulation. Photobiomodulation or near infrared light therapy which
      refers to non-invasive irradiation of tissue with light in the far-red to near
      infrared light spectrum (630-1000 nm), is an intervention that specifically
      targets key mechanisms of RPE dysfunction that are implicated in AMD
      pathogenesis. The current evidence for the efficacy of photobiomodulation in AMD
      is poor but its safety profile and proposed mechanisms of action motivate further
      research as a novel therapy for AMD.

PMID- 29205704
TI  - Hypoglycemia in sulfonylurea-treated KCNJ11-neonatal diabetes: Mild-moderate
      symptomatic episodes occur infrequently but none involving unconsciousness or
      seizures.
AB  - BACKGROUND: Neonatal diabetes mellitus (NDM) caused by mutations in KCNJ11 can be
      successfully treated with high dose oral sulfonylureas; however, little data is
      available on the risk of hypoglycemia. OBJECTIVE: To determine the frequency,
      severity, and clinical significance of hypoglycemia in KCNJ11-related NDM.
      METHODS: Utilizing the University of Chicago Monogenic Diabetes Registry, parents
      completed an online questionnaire addressing hypoglycemia. Continuous glucose
      monitoring (CGM) data was available for 7 subjects. RESULTS: Thirty subjects with
      KCNJ11-related permanent NDM (166 patient-years on sulfonylurea) had median
      sulfonylurea dose of 0.39 mg/kg/day (0.24-0.88 IQR, interquartile range) with
      median HbA1c 5.7% (39 mmol/mol) (5.5-6.1 IQR, 37-43 mmol/mol). Hypoglycemia (<70
      mg/dL) was reported monthly once or less frequently in 89.3% of individuals, but
      3 (10.7%) reported once weekly or more. Of all hypoglycemic episodes reported,
      none involved seizures or unconsciousness and thus did not meet the current ISPAD
      definition of severe hypoglycemia. Seven individuals wore a CGM for a total of
      912 hours with blood sugars falling below 70 mg/dL for 5.8% of the time recorded,
      similar to ranges reported for people without diabetes. CONCLUSIONS: In our
      cohort of KCNJ11-related permanent NDM, hypoglycemia is infrequent and mild
      despite the high doses of sulfonylurea used and near-normal level of glycemic
      control. Long-term follow-up on larger numbers will be required to clarify the
      incidence and determinants of hypoglycemia in this unique population.

PMID- 29205706
TI  - Effect of fermented total mixed rations on the growth performance, carcass and
      meat quality characteristics of Hanwoo steers.
AB  - This study was conducted to assess the effects of fermented total mixed ration
      (FTMR) on the growth performance, carcass and meat quality traits of Hanwoo
      steers. The present study evidenced that the FTMR had a strong effect on dry
      matter intake, body weight, daily gain, slaughter weight and carcass
      characteristics compared with control animals. The results showed that the dry
      matter intake (7.17 +/- 0.13 kg), average body weight (615.20 +/- 112.82 kg), and
      daily gain (0.56 +/- 0.16 kg) were greater in animals receiving FTMR than in
      control animals (P < 0.05). The meat quality characteristics indicated that
      cooking loss and the pH values did not vary between control and FTMR treated
      animals; however, animals in the treated groups (FTMR) had higher meat quality
      grades, carcass weight (396.13 +/- 18.35), fat thickness (13.25 +/- 1.75),
      marbling score (5.63 +/- 0.56), meat color (40.06 +/- 1.23), crude fat (18.39 +/-
      1.32) and sensory characteristics (flavor 5.03 +/- 0.17; tenderness 4.42 +/-
      0.33; juiciness 5.10 +/- 0.16). Nevertheless, the shear force values decreased
      significantly in FTMR-treated animals compared with control group steers.
      Overall, FTMR may not only improve the growth performance, biochemical
      metabolites, and fatty and acetic acid profiles of steers, but may also enhance
      the carcass and meat quality characteristics of Hanwoo steers. Regarding
      economics, our research findings suggest that FTMR-based feeds may enhance Hanwoo
      steer meat quality at a low cost.

PMID- 29205707
TI  - Massed versus spaced practice in vocology: effect of a short-term intensive voice
      training versus a longer-term traditional voice training.
AB  - BACKGROUND: In contrast with most medical and pharmaceutical therapies, the
      optimal dosage for voice therapy or training is unknown. AIMS: The aim of this
      study was to compare the effect of a short-term intensive voice training (IVT)
      with a longer-term traditional voice training (TVT) on the vocal quality and
      vocal capacities of vocally healthy non-professional voice users. METHODS &
      PROCEDURES: A pre-/post-test randomized control group design with follow-up
      measurements was used. Twenty healthy female non-professional voice users with a
      mean age of 21.7 years (range = 20-24 years) were randomly assigned into a short
      term IVT group (n = 10) or a longer-term TVT group (n = 10). Both groups received
      an identical 6-h lasting voice training. Only the distribution of practice varied
      between the groups: 2 h a day for 3 consecutive days for the IVT group versus two
      30-min sessions a week for 6 weeks for the TVT group. In both groups, a voice
      assessment protocol consisting of subjective (questionnaire, participant's self
      report, auditory-perceptual evaluation) and objective (maximum performance task,
      acoustic analysis, voice range profile, dysphonia severity index) measurements
      and determinations was used to evaluate the participants' voice pre- and post
      training and at 6 weeks follow-up. Groups were compared over time using linear
      mixed models and generalized linear mixed models. Within-group effects of time
      were determined using post-hoc pairwise comparisons with Bonferroni corrections.
      OUTCOMES & RESULTS: No significant time-by-group interactions were found for any
      of the outcome measures, indicating no significant differences in evolution over
      time between the groups. Significant time effects were found for maximum
      phonation time, lowest intensity, lowest frequency, highest frequency and
      dysphonia severity index, all improving over time in both groups. More in-depth
      within-group analyses indicate a preference for the IVT group regarding the
      evolution of maximum phonation time, lowest frequency and dysphonia severity
      index, and a preference for the TVT group regarding the evolution of lowest
      intensity. CONCLUSIONS & IMPLICATIONS: Short-term IVT may be equally, or even
      more, effective in training vocally healthy non-professional voice users compared
      with longer-term TVT.

PMID- 29205708
TI  - Temperature-Responsive Luminescent Solar Concentrators: Tuning Energy Transfer in
      a Liquid Crystalline Matrix.
AB  - Temperature-responsive luminescent solar concentrators (LSCs) have been
      fabricated in which the Forster resonance energy transfer (FRET) between a donor
      acceptor pair in a liquid crystalline solvent can be tuned. At room temperatures,
      the perylene bisimide (PBI) acceptor is aggregated and FRET is inactive; while
      after heating to a temperature above the isotropic phase of the liquid crystal
      solvent, the acceptor PBI completely dissolves and FRET is activated. This
      unusual temperature control over FRET was used to design a color-tunable LSC. The
      device has been shown to be highly stable towards consecutive heating and cooling
      cycles, making it an appealing device for harvesting otherwise unused solar
      energy.

PMID- 29205711
TI  - Primary orbital apocrine hidrocystoma with sebaceous elements.

PMID- 29205712
TI  - Quantitative Screening of Cell-Surface Gangliosides by Nondestructive Extraction
      and Hydrophobic Collection.
AB  - A screening strategy involving designed extractors and collectors was used for
      the nondestructive quantitation of gangliosides on cell surfaces. The extractors
      were constructed by functionalizing maleimide silica bubbles with a DNA probe,
      which contains an endonuclease cleavage site and a boronic acid end to extract
      cell-surface sialic acid-containing compounds through simple centrifugation.
      After the extractors containing the extracted compounds were incubated with
      endonuclease, the released oligonucleotide-gangliosides were selectively
      collected by silanized collector bubbles through hydrophobic interactions. The in
      vitro fluorescent signals from the collectors were used for the quantitation of
      cell-surface gangliosides. By combining with sialidase cleavage, a protocol for
      the identification of ganglioside subtypes was developed. The successful
      monitoring of the regeneration of cell-surface gangliosides demonstrates the
      potential of this strategy in probing related biological processes.

PMID- 29205713
TI  - Ultralong Phosphorescence from Organic Ionic Crystals under Ambient Conditions.
AB  - A new type of materials, organic salts in the crystal state, have ultralong
      organic phosphorescence (UOP) under ambient conditions. The change of cations
      (NH4+ , Na+ , or K+ ) in these phosphors gives access to tunable UOP colors
      ranging from sky blue to yellow green, along with ultralong emission lifetimes of
      over 504 ms. Single-crystal analysis reveals that unique ionic bonding can
      promote an ordered arrangement of organic salts in crystal state, which then can
      facilitate molecular aggregation for UOP generation. Additionally, reversible
      ultralong phosphorescence can be realized through the alternative employment of
      fuming gases (ammonia and hydrogen chloride), demonstrating its potential as a
      candidate for visual ammonic or hydrogen chloride gas sensing. The results
      provide an environmental responsible and practicable synthetic approach to
      expanding the scope of ultralong organic phosphorescent materials as well as
      their applications.

PMID- 29205714
TI  - Genetic variants in NTCP exon gene are associated with HBV infection status in a
      Chinese Han population.
AB  - AIM: Sodium taurocholate co-transporting polypeptide (NTCP) plays an important
      role in the enterohepatic circulation of bile acids. Recently, NTCP was
      identified as a hepatitis B virus (HBV) receptor. The aim of this study is to
      investigate the association of NTCP polymorphisms with HBV clinical outcomes and
      investigate the relationship between NTCP polymorphisms and the serum bile acid
      level in a Chinese Han population. METHODS: The single nucleotide polymorphisms
      rs2296651 and rs4646285 were genotyped in 1619 Chinese Han individuals. Improved
      multiple ligase detection reaction was utilized to genotype. The level of bile
      acids was measured by the enzymatic cycling method. Quantitative polymerase chain
      reaction analysis was carried out to analyze the potential function. RESULTS: In
      logistic regression analysis, the frequency of rs2296651 (S267F) CT genotype was
      higher in HBV immune recovery and healthy control groups than in the chronic HBV
      infection group (P = 0.001 and P < 0.001, respectively). Patients who carried
      allele T showed a higher bile acid level than patients who did not carry allele T
      (P = 0.009). The rs4646285 AA genotype was more common in the immune recovery
      group than in the chronic HBV infection group (P = 0.011). No difference in serum
      bile acid was detected between the rs4646285 wild-type patients and mutant-type
      patients. Quantitative reverse transcription-polymerase chain reaction showed the
      NTCP mRNA levels were lower in rs4646285 variants than wild types. CONCLUSION:
      NTCP gene polymorphisms may be associated with the natural course of HBV
      infection in a Chinese Han population. The S267F variant may be a protective
      factor to resist chronic hepatitis B progression which showed a higher bile acid
      level in Chinese Han chronic HBV infection patients. The rs4646285 variants could
      influence the expression of NTCP at the level of transcription, and ultimately
      may be associated with HBV infection immune recovery.

PMID- 29205715
TI  - Photoinduced Intermolecular Electron Transfer Mediated by the Colloidal Tyrosyl
      Bolaamphiphile Assembly.
AB  - The self-assembly of tyrosyl bolaamphiphiles is exploited to create a colloidal
      protein-like host matrix, upon which sacrificial electron-donor molecules
      associate to create a photosystem II (PSII) mimetic electron-relay system. This
      system harnesses the tyrosine phenol groups abundant on the surface of the
      assemblies to mediate photoinduced intermolecular electron transfer. Compared
      with the l-tyrosine molecules, the tyrosyl bolaamphiphile assembly facilitates
      electron transfer from the sacrificial electron donor to the oxidized
      photosensitizer. The enhanced electron relay is likely to be driven by the host
      function of the assembly associated with the sacrificial electron donor and by
      the suppression of the oxidative cross-linking of phenoxyl radicals. The tyrosyl
      bolaamphiphile assembly is advantageous in the construction of a PSII mimetic
      system with a protein-like nature and displaying biochemical functions.

PMID- 29205716
TI  - Effects of Pressure and pH on the Hydrolysis of Cytosine: Implications for
      Nucleotide Stability around Deep-Sea Black Smokers.
AB  - The relatively low chemical stability of cytosine compared with other nucleobases
      is a key concern in origin-of-life scenarios, but the effect of pressure on the
      rate of hydrolysis of cytosine to uracil remains unknown. Through in situ NMR
      spectroscopy measurements, it has been determined that the half-life of cytosine
      at 373.15 K decreases from (18.0+/-0.7) days at ambient pressure (0.1 MPa) to
      (8.64+/-0.18) days at high pressure (200 MPa). This yields an activation volume
      for hydrolysis of (-11.8+/-0.5) cm3  mol-1 ; a decrease that is similar to the
      molar volume of water (18.0 cm3  mol-1 ) and consistent with a tetrahedral 3,3
      hydroxyamine transition-state/intermediate species. Similar behaviour was also
      observed for cytidine. At both ambient and high pressures, the half-life of
      cytosine decreases significantly as the pH decreases from 7.0 to 6.0. These
      results provide scant support for the notion that RNA-based life forms originated
      in high-temperature, high-pressure, acidic environments.

PMID- 29205717
TI  - Manganese(I)-Catalyzed C-H (2-Indolyl)methylation: Expedient Access to
      Diheteroarylmethanes.
AB  - An unprecedented MnI -catalyzed (2-indolyl)methylation of heteroarenes is
      reported. This method makes use of an aromatizing cascade strategy to install a
      (2-indolyl)methyl group into target molecules, thereby leading to the expedient
      synthesis of previously challenging and important unsymmetrical
      diheteroarylmethanes, in particular bis(2-indolyl)methanes. The proposed cascade
      process comprises the reorganization of multiple bonds with controlled
      regioselectivity and high atom economy and can be performed on a gram-scale.
      Furthermore, a metal-free C-H propargylation is observed. The diverse application
      of this method is also demonstrated.

PMID- 29205719
TI  - A cure for bruxism.

PMID- 29205718
TI  - Enantioselective Photochemical Organocascade Catalysis.
AB  - Reported herein is a photochemical cascade process that combines the excited
      state and ground-state reactivity of chiral organocatalytic intermediates. This
      strategy directly converts racemic cyclopropanols and alpha,beta-unsaturated
      aldehydes into stereochemically dense cyclopentanols with exquisite
      stereoselectivity. Mechanistic investigations have enabled elucidating the origin
      of the stereoconvergence, which is governed by a kinetic resolution process.

PMID- 29205720
TI  - Borderline hits the diagnostic buffers again.

PMID- 29205721
TI  - Prophylactic mood stabilization: What is the evidence for lithium exposure in
      drinking water?

PMID- 29205722
TI  - Bipolar II disorder.

PMID- 29205723
TI  - Differential diagnosis of bipolar disorder and borderline personality disorder.

PMID- 29205724
TI  - Growth modeling of the green microalga Scenedesmus obliquus in a hybrid
      photobioreactor as a practical tool to understand both physical and biochemical
      phenomena in play during algae cultivation.
AB  - In recent years, numerous studies have justified the use of microalgae as a
      sustainable alternative for the generation of different types of fuels, food
      supplementation, and cosmetics, as well as bioremediation processes. To improve
      the cost/benefit ratio of microalgae mass production, many culture systems have
      been built and upgraded. Mathematical modeling the growth of different species in
      different systems has become an efficient and practical tool to understand both
      physical and biochemical phenomena in play during algae cultivation. In addition,
      growth modeling can guide design changes that lead to process optimization. In
      the present work, growth of the green microalga Scenedesmus obliquus was modeled
      in a hybrid photobioreactor that combines the characteristics of tubular
      photobioreactors (TPB) with thin-layer cascades (TLC). The system showed
      productivity greater than 8.0 g m-2 day-1 (dry mass) for CO2 -fed cultures, and
      the model proved to be an accurate representation of experimental data with R2
      greater than 0.7 for all cases under variable conditions of temperature and
      irradiance to determine subsystem efficiency. Growth modeling also allowed growth
      prediction relative to the operating conditions of TLC, making it useful for
      estimating the system given other irradiance and temperature conditions, as well
      as other microalgae species.

PMID- 29205725
TI  - Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate
      its mitochondrial translocation and subsequent mitophagy.
AB  - Chronic myeloid leukemia (CML) is caused by the chimeric protein p210 BCR-ABL
      encoded by a gene on the Philadelphia chromosome. Although the kinase domain of
      p210 BCR-ABL is an active driver of CML, the pathological role of its pleckstrin
      homology (PH) domain remains unclear. Here, we carried out phospholipid vesicle
      binding assays to show that cardiolipin (CL), a characteristic mitochondrial
      phospholipid, is a unique ligand of the PH domain. Arg726, a basic amino acid in
      the ligand-binding region, was crucial for ligand recognition. A subset of wild
      type p210 BCR-ABL that was transiently expressed in HEK293 cells was dramatically
      translocated from the cytosol to mitochondria in response to carbonyl cyanide m
      chlorophenylhydrazone (CCCP) treatment, which induces mitochondrial
      depolarization and subsequent externalization of CL to the organelle's outer
      membrane, whereas an R726A mutant of the protein was not translocated.
      Furthermore, only wild-type p210 BCR-ABL, but not the R726A mutant, suppressed
      CCCP-induced mitophagy and subsequently enhanced reactive oxygen species
      production. Thus, p210 BCR-ABL can change its intracellular localization via
      interactions between the PH domain and CL to cope with mitochondrial damage. This
      suggests that p210 BCR-ABL could have beneficial effects for cancer
      proliferation, providing new insight into the PH domain's contribution to CML
      pathogenesis.

PMID- 29205726
TI  - Total Synthesis of Maoecrystal P: Application of a Strained Bicyclic Synthon.
AB  - A new strategy was devised for the total synthesis of highly oxidized ent
      kauranoids. A highly regio- and diastereoselective intermolecular Diels-Alder
      cycloaddition involving a diene embedded in a substituted bicyclo[4.1.0] skeleton
      was used to assemble all carbon centers but C17 of the target molecule at an
      early stage of the synthesis. Subsequent synthetic steps, including redox
      manipulations, SmI2 -mediated cyclization, and isomerization reactions, afforded
      the antitumor natural product maoecrystal P.

PMID- 29205729
TI  - Tropical Medicine & International Health.

PMID- 29205727
TI  - Covalent Organic Frameworks and Cage Compounds: Design and Applications of
      Polymeric and Discrete Organic Scaffolds.
AB  - Porous organic materials are an emerging class of functional nanostructures with
      unprecedented properties. Dynamic covalent assembly of small organic building
      blocks under thermodynamic control is utilized for the intriguingly simple
      formation of complex molecular architectures in one-pot procedures. In this
      Review, we aim to analyze the basic design principles that govern the formation
      of either covalent organic frameworks as crystalline porous polymers or covalent
      organic cage compounds as shape-persistent molecular objects. Common synthetic
      procedures and characterization techniques will be discussed as well as more
      advanced strategies such as postsynthetic modification or self-sorting. When
      appropriate, comparisons are drawn between polymeric frameworks and discrete
      organic cages in terms of their underlying properties. Furthermore, we highlight
      the potential of these materials for applications ranging from gas storage to
      catalysis and organic electronics.

PMID- 29205730
TI  - Triangles and Squares for a Unique Molecular Crystal Structure: Unsupported Two
      Coordinate Lithium Cations and CC Agostic Interactions in Cyclopropyllithium
      Derivatives.
AB  - Understanding and controlling the aggregation state is germane to alkyllithium
      chemistry. Lewis base-free alkyllithium compounds normally form tetrahedral
      tetramers or octahedral hexamers in the solid state with the lithium cations
      being three-coordinate. We report that the unsupported cyclopropyl derivative 1
      (trimethylsilyl)cyclopropyllithium [{MU-c-C(SiMe3 )C2 H4 }Li]4 (1), synthesized
      by the reduction of 1-(phenylthio)-1-(trimethylsilyl)cyclopropane, crystallizes
      as a tetramer in the space group I-4 with the two-coordinate lithium atoms
      forming a square. CC agostic interactions complete the coordination sphere around
      each lithium. The aggregate is preserved in hydrocarbon solution. Furthermore, CC
      agostic interactions compete intra- and intermolecularly with Lewis base donation
      as in the unsaturated dimer of 1-(phenylthio)cyclopropyllithium [Li(thf)2 {MU-c
      C(SPh)C2 H4 }2 Li (thf)] (3) which is also fully characterized.

PMID- 29205731
TI  - Paracaecal hernia: uncommon but important cause of small bowel obstruction
      successfully managed with laparoscopic surgery.

PMID- 29205732
TI  - Azophenine as Central Core for Efficient Light Harvesting Devices.
AB  - The notoriously non-luminescent uncycled azophenine (Q) was harnessed with Bodipy
      and zinc(II)porphyrin antennas to probe its fluorescence properties, its ability
      to act as a singlet excited state energy acceptor and to mediate the transfer.
      Two near-IR emissions are depicted from time-resolved fluorescence spectroscopy,
      which are most likely due to the presence of tautomers of very similar calculated
      total energies (350 cm-1 ; DFT; B3LYP). The rates for energy transfer, kET (S1 ),
      for 1 Bodipy*->Q are in the order of 1010 -1011  s-1 and are surprisingly fast
      when considering the low absorptivity properties of the lowest energy charge
      transfer excited state of azophenine. The rational is provided by the calculated
      frontier molecular orbitals (MOs) which show atomic contributions in the C6 H4
      C=CC6 H4 arms, thus favoring the double electron exchange mechanism. In the mixed
      antenna Bodipy-porphyrin star molecule, the rate for 1 Bodipy*->porphyrin has
      also been evaluated (~16*1010  s-1 ) and is among the fastest rates reported for
      Bodipy-zinc(II)porphyrin pairs. This astonishing result is again explained from
      the atomic contributions of the C6 H4 C=CC6 H4 and C=CC6 H4 arms thus favouring
      the Dexter process. Here, for the first time, this process is found to be
      sensitively temperature-dependent. The azophenine turns out to be excellent for
      electronic communication.

PMID- 29205733
TI  - Borazine-CF3- Adducts for Rapid, Room Temperature, and Broad Scope
      Trifluoromethylation.
AB  - A fluoroform-derived borazine CF3- transfer reagent is used to effect rapid
      nucleophilic reactions in the absence of additives, within minutes at 25  degrees
      C. Inorganic electrophiles spanning seven groups of the periodic table can be
      trifluoromethylated in high yield, including transition metals used for catalytic
      trifluoromethylation. Organic electrophiles included (hetero)arenes, enabling C-H
      and C-X trifluoromethylation reactions. Mechanistic analysis supports a
      dissociative mechanism for CF3- transfer, and cation modification afforded a
      reagent with enhanced stability.

PMID- 29205734
TI  - Clinical correlates of hypoglycaemia over 4 years in people with type 2 diabetes
      starting insulin: An analysis from the CREDIT study.
AB  - AIM: To identify factors associated with documented symptomatic and severe
      hypoglycaemia over 4 years in people with type 2 diabetes starting insulin
      therapy. MATERIALS AND METHODS: CREDIT, a prospective international observational
      study, collected data over 4 years on people starting any insulin in 314 centres;
      2729 and 2271 people had hypoglycaemia data during the last 6 months of years 1
      and 4, respectively. Multivariable logistic regression was used to select the
      characteristics associated with documented symptomatic hypoglycaemia, and the
      model was tested against severe hypoglycaemia. RESULTS: The proportions of
      participants reporting >=1 non-severe event were 18.5% and 16.6% in years 1 and
      4; the corresponding proportions of those achieving a glycated haemoglobin
      (HbA1c) concentration <7.0% (<53 mmol/mol) were 24.6% and 18.3%, and 16.5% and
      16.2% of those who did not. For severe hypoglycaemia, the proportions were 3.0%
      and 4.6% of people reaching target vs 1.5% and 1.1% of those not reaching target.
      Multivariable analysis showed that, for documented symptomatic hypoglycaemia at
      both years 1 and 4, baseline lower body mass index and more physical activity
      were predictors, and lower HbA1c was an explanatory variable in the respective
      year. Models for documented symptomatic hypoglycaemia predicted severe
      hypoglycaemia. Insulin regimen was a univariate explanatory variable, and was not
      retained in the multivariable analysis. CONCLUSIONS: Hypoglycaemia occurred at
      significant rates, but was stable over 4 years despite increased insulin doses.
      The association with insulin regimen and with oral agent use declined over that
      time. Associated predictors and explanatory variables for documented symptomatic
      hypoglycaemia conformed to clinical impressions and could be extended to severe
      hypoglycaemia. Better achieved HbA1c was associated with a higher risk of
      hypoglycaemia.

PMID- 29205736
TI  - Functional screening devices for diabetic retinopathy.

PMID- 29205735
TI  - Stereoselective Total Synthesis of Hetisine-type C20 -Diterpenoid Alkaloids:
      Spirasine IV and XI.
AB  - The first total synthesis of the architecturally complex hetisine-type
      heptacyclic C20 -diterpenoid alkaloids (+/-)-spirasine IV and XI is reported. The
      A/F/G/C tetracyclic skeleton with the challenging N-C6 and C14-C20 linkages was
      efficiently constructed by an intramolecular azomethine-ylide-based 1,3-dipolar
      cycloaddition with unusual regioselectivity. SmI2 -mediated free-radical addition
      to the arene moiety without prior dearomatization and a stereoselective
      intramolecular aldol reaction further enabled rapid access to the hetisine core,
      providing a bicyclo[2.2.2]octane ring with a new oxygen substitution pattern.

PMID- 29205737
TI  - Combined treatment approach to chronic anal fissure with associated anal fistula.
AB  - BACKGROUND: Anal fistula in association with chronic anal fissure (fissure
      fistula) is infrequently described. Recognizing this association and managing
      both components may help prevent some treatment failures seen with chronic anal
      fissure. This study aims to report on the outcomes of 20 consecutive patients
      with fissure-fistula managed with fistulotomy and injection of botulinum A toxin.
      METHODS: The study is a retrospective, observational study, assessing the success
      of symptom resolution following fistulotomy with botulinum A toxin, in patients
      identified as having a chronic anal fissure with associated anal fistula. The
      study included all patients with this condition treated with combination
      treatment by a single surgeon at a tertiary care hospital between January 2013
      and January 2016. RESULTS: Twenty patients with fissure-fistula treated with
      fistulotomy and botulinum toxin A were identified. The median cohort age was 44
      years (range 25-78), with a predominance of males (80%) and posterior fissure
      position (80%). The most common presenting symptoms were anal pain (70%), rectal
      bleeding (55%), anal discharge (35%) and anal pruritus (35%). Mean follow-up was
      10.5 weeks and all patients who attended follow-up appointments reported
      resolution of symptoms. There were no cases of incontinence and none of the
      cohort required further surgical intervention for the condition. CONCLUSION:
      Chronic anal fissure with associated anal fistula can be successfully managed
      with fistulotomy and injection of botulinum toxin A. Further studies would be
      helpful in determining if recognition and management of the fistula component in
      isolation with fistulotomy is as effective as fistulotomy plus botulinum A toxin.

PMID- 29205738
TI  - Improving HSAPO-34 Methanol-to-Olefin Turnover Capacity by Seeding the
      Hydrocarbon Pool.
AB  - Seeding the hydrocarbon pool before exposure to methanol ensures the presence of
      active olefinic and aromatic chain carriers in the HSAPO-34 cavity before the
      first methanol-to-olefin turnover. The primordial hydrocarbon pool enables the
      introduction, at low turnover numbers, of chain propagation steps that compete
      with methanol transfer dehydrogenation-mediated chain termination steps, thereby
      increasing the fraction of converted methanol used for productive turnovers
      during methanol-to-olefin catalysis over HSAPO-34. Seeding the hydrocarbon pool
      results, concurrently, in higher light-olefin yields and lower rates of carbon
      loss. The increasing relative preponderance of methanol transfer dehydrogenation
      steps with increasing methanol pressure renders seeding more effective at higher
      methanol pressures. Under the conditions used in this study, seeding appears to
      accelerate the buildup of the hydrocarbon pool without significantly altering its
      composition. The results reported here outline a strategy for mitigating the
      deleterious effects of methanol transfer dehydrogenation reactions while
      reemphasizing their primacy in effecting catalyst deactivation during methanol-to
      olefins conversion.

PMID- 29205739
TI  - The use of psychiatry-focused simulation in undergraduate nursing education: A
      systematic search and review.
AB  - Evidence on the use of simulation to teach psychiatry and mental health
      (including addiction) content is emerging, yet no summary of the implementation
      processes or associated outcomes exists. The aim of this study was to
      systematically search and review empirical literature on the use of psychiatry
      focused simulation in undergraduate nursing education. Objectives were to (i)
      assess the methodological quality of existing evidence on the use of simulation
      to teach mental health content to undergraduate nursing students, (ii) describe
      the operationalization of the simulations, and (iii) summarize the associated
      quantitative and qualitative outcomes. We conducted online database (MEDLINE,
      Embase, ERIC, CINAHL, PsycINFO from January 2004 to October 2015) and grey
      literature searches. Thirty-two simulation studies were identified describing and
      evaluating six types of simulations (standardized patients, audio simulations,
      high-fidelity simulators, virtual world, multimodal, and tabletop). Overall, 2724
      participants were included in the studies. Studies reflected a limited number of
      intervention designs, and outcomes were evaluated with qualitative and
      quantitative methods incorporating a variety of tools. Results indicated that
      simulation was effective in reducing student anxiety and improving their
      knowledge, empathy, communication, and confidence. The summarized qualitative
      findings all supported the benefit of simulation; however, more research is
      needed to assess the comparative effectiveness of the types of simulations.
      Recommendations from the findings include the development of guidelines for
      educators to deliver each simulation component (briefing, active simulation,
      debriefing). Finally, consensus around appropriate training of facilitators is
      needed, as is consistent and agreed upon simulation terminology.

PMID- 29205740
TI  - Chemoselectivity Control in the Asymmetric Hydrogenation of gamma- and delta-Keto
      Esters into Hydroxy Esters or Diols.
AB  - The asymmetric hydrogenation of aromatic gamma- and delta-keto esters into
      optically active hydroxy esters or diols under the catalysis of a novel
      DIPSkewphos/3-AMIQ-RuII complex was studied. Under the optimized conditions (8
      atm H2  , Ru complex/t-C4 H9 OK=1:3.5, 25  degrees C) the gamma- and delta
      hydroxy esters (including gamma-lactones) were obtained quantitatively with 97-99
      % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2 
      , [t-C4 H9 OK]=50 mm, 40  degrees C), the 1,4- and 1,5-diols were obtained
      predominantly with 95-99 % ee. The reactivity of the ester group was notably
      dependent on the length of the carbon spacer between the two carbonyl moieties of
      the substrate. The reaction of beta- and epsilon-keto esters selectively afforded
      the hydroxy esters regardless of the reaction conditions. This catalyst system
      was applied to the enantioselective and regioselective (for one of the two ester
      groups) hydrogenation of a gamma-epsilon-diketo diester into a trihydroxy ester.

PMID- 29205741
TI  - Standoff Mid-Infrared Emissive Imaging Spectroscopy for Identification and
      Mapping of Materials in Polychrome Objects.
AB  - Microscale mid-infrared (mid-IR) imaging spectroscopy is used for the mapping of
      chemical functional groups. The extension to macroscale imaging requires that
      either the mid-IR radiation reflected off or that emitted by the object be
      greater than the radiation from the thermal background. Reflectance spectra can
      be obtained using an active IR source to increase the amount of radiation
      reflected off the object, but rapid heating of greater than 4  degrees C can
      occur, which is a problem for paintings. Rather than using an active source, by
      placing a highly reflective tube between the painting and camera and introducing
      a low temperature source, thermal radiation from the room can be reduced,
      allowing the IR radiation emitted by the painting to dominate. Thus, emissivity
      spectra of the object can be recovered. Using this technique, mid-IR emissivity
      image cubes of paintings were collected at high collection rates with a low
      noise, line-scanning imaging spectrometer, which allowed pigments and paint
      binders to be identified and mapped.

PMID- 29205742
TI  - Trends in outpatient anti-arrhythmic prescriptions for atrial fibrillation and
      left atrial ablation in Australia: 1997-2016.
AB  - BACKGROUND: An important aspect of atrial fibrillation (AF) management is the
      decision whether to adopt a rate or rhythm control strategy. Options for the
      latter include oral anti-arrhythmic drugs (AAD) or catheter ablation. AIM: To
      describe the trends in rhythm control for AF in Australia between 1997 and 2016.
      METHODS: We conducted a retrospective study using prospectively collected data
      between 1997 and 2016 from the Pharmaceutical Benefit Scheme and Medicare Benefit
      Schedule websites, which, respectively, contain information pertaining to public
      AAD prescriptions and rebatable AF ablation procedures performed in Australia.
      RESULTS: Sotalol and amiodarone remain the most commonly prescribed AAD in
      Australia, although their use is decreasing. Rates of catheter ablation for AF
      continue to rise annually with a 48-fold increase from 71 to 3480 since 1997.
      CONCLUSION: A rhythm control strategy is frequently utilised for AF management in
      Australia. Consistent with international guidelines which advocate safety over
      efficacy when choosing a rhythm control strategy, the prescriptions of amiodarone
      have been consistently decreasing since 2002, whereas sotalol and flecainide
      prescriptions have largely increased, with a peak in 2015. Catheter ablation per
      capita has burgeoned 36-fold.

PMID- 29205743
TI  - Rotational atherectomy and new-generation drug-eluting stent implantation.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of
      rotational atherectomy (RA) followed by new-generation drug-eluting stent (DES)
      implantation in patients with an extensive amount of calcified and fibrotic
      plaque. BACKGROUND: RA followed by new-generation DES implantation for complex
      lesions has not been thoroughly evaluated. METHODS: A total of 744 consecutive
      patients (770 lesions) treated with new-generation DES implantation following RA
      for de novo lesions between January 2013 and November 2015 were retrospectively
      identified using our institutional database. Clinical outcomes at 12 months were
      evaluated and the independent predictors of all-cause death and target vessel
      failure (TVF) were assessed using Cox regression models. RESULTS: Target lesion
      revascularization occurred in 22 lesions (2.9%) and TVF occurred in 51 lesions
      (6.6%). In a multivariate analysis, hemodialysis, non-ST-segment elevation acute
      coronary syndrome, low ejection fraction, and HbA1c ? 7% were associated with 12
      month mortality. Hemodialysis and right coronary artery were identified as
      independent predictors of TVF (hazard ratio (HR) 4.107, 95% confidence interval
      (CI) 2.194-7.685, P < .001; HR 2.491, 95% CI 1.023-6.062, P = .044,
      respectively). CONCLUSIONS: A good debulking with RA followed by new-generation
      DES implantation is recommended for patients with an excessive amount of
      calcified and fibrotic plaque, as this will likely improve the clinical outcomes.

PMID- 29205744
TI  - Rabbits with naturally occurring cataracts referred for phacoemulsification and
      intraocular lens implantation: a preliminary study of 12 cases.
AB  - OBJECTIVE: To describe the presentation of 15 rabbits with naturally occurring
      cataracts referred for phacoemulsification surgery, the procedure in 13 cases and
      the follow-up in 12. ANIMALS INCLUDED: Fifteen rabbits (30 eyes), nine of which
      stopped following visual cues in association with cataract progression. MATERIALS
      AND METHODS: Rabbits underwent preoperative ophthalmic and ocular ultrasound
      examination. RESULTS: Thirteen rabbits (22 eyes) had mature cataracts. Ten were
      bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The
      cataract in one of these was incipient. One rabbit had bilateral immature
      cataracts. One rabbit had a subluxated lens, and one had a retinal detachment.
      Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm
      capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet(r) , Berlin,
      Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D
      20S-models. Intraoperative complications included one unilateral posterior
      capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One
      rabbit died during anesthetic recovery. Nine cases were PCR-tested for
      Encephalitozoon cuniculi, and only three were positive. The median follow-up time
      was 12 months (4-24 months). Rabbits that were not following visual cues
      preoperatively did so postoperatively, and surgery resulted in a clear visual
      axis for the follow-up period in every case except in two, due to reasons other
      than the surgery. CONCLUSIONS: Phacoemulsification with CTR and IOL implantation
      offers good long-term results and can improve the quality of life of pet rabbits.
      Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic
      death are potential complications.

PMID- 29205745
TI  - Increasing Catalyst Efficiency in C-H Activation Catalysis.
AB  - C-H activation reactions with high catalyst turnover numbers are still very rare
      in the literature and 10 mol % is a common catalyst loading in this field. We
      offer a representative overview of efficient C-H activation catalysis to
      highlight this neglected aspect of catalysis development and inspire future
      effort towards more efficient C-H activation. Examples ranging from palladium
      catalysis, Cp*RhIII - and Cp*CoIII -catalysis, the C-H borylation and silylation
      to methane C-H activation are presented. In these reactions, up to tens of
      thousands of catalyst turnovers have been observed.

PMID- 29205746
TI  - Well-Defined Chiral Gold(III) Complexes: New Opportunities in Asymmetric
      Catalysis.
AB  - Square way to heaven: As a result of their square-planar geometry, the reactive
      site of gold(III) complexes is much closer to the ancillary ligands. This offers
      new perspectives in asymmetric catalysis, as recently evidenced by the groups of
      Wong and Toste with well-defined chiral complexes.

PMID- 29205747
TI  - Dichotomy of Manganese Catalysis via Organometallic or Radical Mechanism:
      Stereodivergent Hydrosilylation of Alkynes.
AB  - Herein, we disclose the first manganese-catalyzed hydrosilylation of alkynes
      featuring diverse selectivities. The highly selective formation of E-products was
      achieved by using mononuclear MnBr(CO)5 with the arsenic ligand, AsPh3 . Whereas
      using the dinuclear catalyst Mn2 (CO)10 and LPO (dilauroyl peroxide) enabled the
      reversed generation of Z-products in good to excellent stereo- and
      regioselectivity. Such a way of controlling the reaction stereoselectivity is
      unprecedented. Mechanistic experiments revealed the dichotomy of manganese
      catalysis via organometallic and radical pathways operating in the E- and Z
      selective routes, respectively.

PMID- 29205748
TI  - Cosmetic tourism for breast augmentation: a systematic review.
AB  - BACKGROUND: The medical tourism industry, and in particular cosmetic tourism for
      breast augmentation, is becoming an increasingly popular global phenomenon. The
      objective of this study is to determine the extent of medical literature and the
      patient risk profiles associated with cosmetic tourism for breast augmentation
      both locally and abroad. DATA SOURCES: OVID MEDLINE, OVID Embase, Cochrane
      Central and Proquest electronic databases. METHODS: The search was conducted
      through to April 2017. Studies pertaining entirely or partly to cosmetic tourism
      for breast augmentation were considered for inclusion. Exclusion criteria
      included non-English articles, studies relating to non-cosmetic or non-implant
      breast augmentation, and studies that did not separately report on findings
      associated with breast augmentation abroad. RESULTS: We identified 17
      observational studies. Common destinations included Europe, South America and
      South East Asia. Infectious complications were common. Wound dehiscence and
      aesthetic dissatisfaction also featured. Catastrophic outcomes such as sepsis,
      intubation and ventilation, radical bilateral mastectomy, irreversible hypoxic
      brain injury and death were also reported. There were expectations that home
      country health systems would treat complications and provide non-medically
      indicated revision procedures. The burden on home country health systems was
      evident from a public health perspective. CONCLUSION: Determining the extent of
      cosmetic tourism for breast augmentation, including outcomes and complications,
      will help to inform Australian patients who this seek procedure abroad.
      Furthermore, it will aid in better understanding the health system implications
      and may help to guide future research and public health interventions both
      locally and internationally.

PMID- 29205749
TI  - Unprecedented Ionization Processes in Mass Spectrometry Provide Missing Link
      between ESI and MALDI.
AB  - In the field of mass spectrometry, producing intact, highly-charged protein ions
      from surfaces is a conundrum with significant potential payoff in application
      areas ranging from biomedical to clinical research. Here, we report on the
      ability to form intact, highly-charged protein ions on high vacuum time-of-flight
      mass spectrometers in the linear and reflectron modes achievable using
      experimental conditions that allow effective matrix removal from both the sample
      surfaces and from the charged clusters formed by the laser ablation event. The
      charge states are the highest reported on high vacuum mass spectrometers, yet
      they remain at only around a third of the highest charge obtained using laser
      ablation with a suitable matrix at atmospheric pressure. Other than physical
      instrument modifications, the key to forming abundant and stable highly-charged
      ions appears to be the volatility of the matrix used. Cumulative results suggest
      mechanistic links between the ionization process reported here and traditional
      ionization methods of electrospray ionization and matrix-assisted laser
      desorption/ionization.

PMID- 29205750
TI  - Spatially distinct, temporally stable microbial populations mediate
      biogeochemical cycling at and below the seafloor in hydrothermal vent fluids.
AB  - At deep-sea hydrothermal vents, microbial communities thrive across geochemical
      gradients above, at, and below the seafloor. In this study, we determined the
      gene content and transcription patterns of microbial communities and specific
      populations to understand the taxonomy and metabolism both spatially and
      temporally across geochemically different diffuse fluid hydrothermal vents. Vent
      fluids were examined via metagenomic, metatranscriptomic, genomic binning, and
      geochemical analyses from Axial Seamount, an active submarine volcano on the Juan
      de Fuca Ridge in the NE Pacific Ocean, from 2013 to 2015 at three different
      vents: Anemone, Marker 33, and Marker 113. Results showed that individual vent
      sites maintained microbial communities and specific populations over time, but
      with spatially distinct taxonomic, metabolic potential, and gene transcription
      profiles. The geochemistry and physical structure of each vent both played
      important roles in shaping the dominant organisms and metabolisms present at each
      site. Genomic binning identified key populations of SUP05, Aquificales and
      methanogenic archaea carrying out important transformations of carbon, sulfur,
      hydrogen, and nitrogen, with groups that appear unique to individual sites. This
      work highlights the connection between microbial metabolic processes, fluid
      chemistry, and microbial population dynamics at and below the seafloor and
      increases understanding of the role of hydrothermal vent microbial communities in
      deep ocean biogeochemical cycles.

PMID- 29205751
TI  - LH-21 and abnormal cannabidiol improve beta-cell function in isolated human and
      mouse islets through GPR55-dependent and -independent signalling.
AB  - AIMS: To examine the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1
      antagonist) on human and mouse islet function, and to determine signalling via
      GPR55 using islets from GPR55-/- mice. MATERIALS AND METHODS: Islets isolated
      from human organ donors and mice were incubated in the absence or presence of Abn
      CBD or LH-21, and insulin secretion, [Ca2+ ]i, cAMP, apoptosis, beta-cell
      proliferation and CREB and AKT phosphorylation were examined using standard
      techniques. RESULTS: Abn-CBD potentiated glucose-stimulated insulin secretion and
      elevated [Ca2+ ]i in human islets and islets from both GPR55+/+ and GPR55-/-
      mice. LH-21 also increased insulin secretion and [Ca2+ ]i in human islets and
      GPR55+/+ mouse islets, but concentrations of LH-21 up to 0.1 MUM were ineffective
      in islets from GPR55-/- mice. Neither ligand affected basal insulin secretion or
      islet cAMP levels. Abn-CBD and LH-21 reduced cytokine-induced apoptosis in human
      islets and GPR55+/+ mouse islets, and these effects were suppressed after GPR55
      deletion. They also increased beta-cell proliferation: the effects of Abn-CBD
      were preserved in islets from GPR55-/- mice, while those of LH-21 were abolished.
      Abn-CBD and LH-21 increased AKT phosphorylation in mouse and human islets.
      CONCLUSIONS: This study showed that Abn-CBD and LH-21 improve human and mouse
      islet beta-cell function and viability. Use of islets from GPR55-/- mice suggests
      that designation of Abn-CBD and LH-21 as a GPR55 agonist and a CB1 antagonist,
      should be revised.

PMID- 29205752
TI  - In vitro stimulatory effect of N-acetyl tryptophan-glucopyranoside against gamma
      radiation induced immunosuppression.
AB  - Radiation-induced manifestations like free radical burst, oxidative damage and
      apoptosis leading to cell death. In present study, N-acetyl tryptophan
      glucopyranoside (NATG) was assessed for its immune-radioprotective activities
      using J774A.1 cells. Clonogenic cell survival, cell cycle progression and
      cytokines i.e. IFN-gamma, TNF-alpha, IL-2, IL-10, IL-12, IL-13 and IL-17A
      expression were evaluated in irradiated and NATG pretreated cells using
      clonogenic formation ability, flow cytometry and ELISA assay. Results indicated
      that 0.25MUg/ml NATG exhibited maximum radioprotection against gamma-radiation
      (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus
      irradiated cells showed significant elevation in IFN-gamma (~38.2%), IL-17A
      (~53.7%) and IL-12 (~58.8%) expression as compared to only irradiated cells.
      Conversely, significant decrease in TNF-alpha (~21.6%), IL-10 (~31.2%), IL-2
      (~23.7%) and IL-13 expression (~17.8%) were observed in NATG pretreated plus
      irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment
      to irradiated J774A.1 cells, stimulate Th1 while diminish Th2 cytokines that
      contributes to radioprotection.

PMID- 29205753
TI  - Prognostic significance of pre-operative inflammatory markers in resected
      gallbladder cancer: a systematic review.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP) and
      Glasgow Prognostic Score (GPS) have demonstrated good prognostic value in several
      cancers but their role in gallbladder cancer (GBC) remains unclear. The aim of
      this study is to systematically review the current literature to determine their
      role in predicting survival outcomes in GBC. METHODS: Using a pre-specified
      inclusive search strategy MEDLINE, EMBASE and CINAHL databases were used to
      identify studies describing survival in patients after GBC resection with high or
      low pre-operative CRP, GPS or NLR. A proforma was used to extract study author
      and date, number of patients, age, gender, tumour stage, use of adjuvant therapy
      and primary outcome data. RESULTS: In all, 46 studies were identified after
      initial screening with four studies reporting survival outcomes. All studies
      described a reduction in survival in patients with an elevated NLR, GPS or CRP.
      Three studies showed NLR to be an independent prognostic marker and one study
      additionally demonstrated that elevated CRP and GPS were associated with poorer
      survival. CONCLUSIONS: Elevated pre-operative inflammatory markers are inversely
      related to survival outcomes. They are relatively inexpensive, easy measurable
      parameters that could aid in the decision making process involved in the
      management of GBC. Sub-stratification of groups utilizing inflammatory markers
      may help guide surgical strategy. However, these studies are retrospective and of
      low to moderate quality. High quality, prospective studies with well-defined
      inclusion criteria and outcomes are needed to guide the role of inflammatory
      markers in the management of GBC.

PMID- 29205754
TI  - Preliminary investigation of blood concentrations of insulin-like growth factor,
      insulin, lactate and beta-hydroxybutyrate in dogs with lymphoma as compared with
      matched controls.
AB  - It is well established that tumour cells have metabolic differences when compared
      with normal cells. This is particularly true for energy metabolism in which dogs
      with cancer have been reported to have higher blood insulin and lactate
      concentrations than control dogs. Moreover, some human and animal studies suggest
      that the insulin-like growth factor 1 (IGF-1) signalling pathway may play a role
      in tumorigenesis and tumour progression. At present, IGF-1 has not been evaluated
      in dogs with multicentric lymphoma. In this prospective, cross-sectional study,
      blood levels of IGF-1, as well as other markers of energy metabolism-insulin,
      glucose, lactate, and beta-hydroxybutyrate-were measured in 16 dogs with
      histologically or cytologically confirmed treatment-naive lymphoma. These results
      were compared with 16 age-, sex- and weight-matched healthy controls. Dietary
      histories were collected, and protein, fat and carbohydrate intake were compared
      between groups. Results demonstrated that IGF-1, insulin, glucose and
      insulin:glucose ratio were not different between groups. However, lactate and
      beta-hydroxybutyrate were higher in the dogs with lymphoma than that in the
      control dogs (1.74 +/- 0.83 mmoL/L vs 1.08 +/- 0.27 and 2.59 +/- 0.59 mmol/L vs
      0.77 +/- 0.38 mmol/L, respectively). Median dietary protein, fat and
      carbohydrates did not differ between the groups. This preliminary study suggests
      that higher insulin and IGF-1 levels relative to controls may not be a consistent
      finding in dogs with lymphoma. The significance of increased beta-hydroxybutyrate
      in dogs with lymphoma warrants further investigation in a larger prospective
      study.

PMID- 29205755
TI  - Short-term outcomes of paediatric liver transplant recipients after transition to
      Adult Healthcare Service.
AB  - BACKGROUND & AIMS: Survival rates after liver transplantation (LT) in paediatric
      recipients have significantly improved over time. However, data regarding
      outcomes after transition from Paediatric to Adult Healthcare Service (AHS) are
      still lacking. Therefore, we aimed to prospectively evaluate the outcome of LT
      recipients after transition, to access patients' non-adherence and identify
      potential risk factors for non-adherence. METHODS: All consecutive adolescent LT
      recipients moving to the AHS at Padua University Hospital were evaluated between
      2010 and 2015. Demographic data, liver function tests, incidence of acute or
      chronic rejection episodes and adherence to medical prescription, were
      prospectively evaluated. An educational pilot study was implemented since 2015 to
      foster adherence during transition. RESULTS: In all, 32 patients (M/F 16/16,
      median age: 23 years) were evaluated. Median interval time between LT and
      transition was 15 years (range: 1-26 years). The main indication for LT was
      biliary atresia (31%), whereas immunosuppression regimen was tacrolimus-based in
      75%. After a median follow-up of 29 months (range: 12-83), no significant
      modifications of liver function tests were observed. Biopsy-proven chronic
      rejection was diagnosed in 6/32 (18%) of patients, who had higher standard
      deviation of tacrolimus trough level than patients without (1.5 vs 1, P = .03).
      Non-adherence was reported in 8/32 (25%) of patients and was significantly
      associated with alcohol consumption (P = .003). Patient and graft survival were
      96% and 93%, respectively. CONCLUSIONS: Adolescent LT patients who undergo
      transition to the AHS have good long-term outcomes. However, a multidisciplinary
      approach aiming at fostering adherence should be used.

PMID- 29205756
TI  - Magnetic Interaction Observed in Hetero Biradical Derivatives Containing a
      2,2,5,5-Tetramethylpyrrolin-1-yloxyl Unit as a Localized Spin Center.
AB  - The magneto-structural correlation of hetero biradical derivatives containing a
      2,2,5,5-tetramethylpyrrolin-1-yloxyl unit as a localized spin center and a
      verdazyl or nitronyl nitroxide radical is reported. The magnetic susceptibility
      measurement revealed that the verdazyl attached biradical 1 exhibits
      ferromagnetic interaction, whereas antiferromagnetic interaction is observed for
      nitronyl nitroxide attached biradical 2. An EPR study in toluene glass matrix
      suggests that both 1 and 2 have a ground triplet state. DFT calculations predict
      that there is intramolecular ferromagnetic interaction for both biradicals. The
      computation also suggests that the intramolecular magnetic interaction is weaker
      with larger dihedral angle between pyrroline ring and verdazyl ring/O-N-C-N-O
      plane of nitronyl nitroxide. The computations of model compounds 3 and 4 suggest
      that spin polarization on vinylic moiety without distribution of SOMO might be an
      essential condition for the intramolecular ferromagnetic interaction.

PMID- 29205757
TI  - Enhancing metabolic monitoring for children and adolescents using second
      generation antipsychotics.
AB  - The prevalence of children and adolescents using second-generation antipsychotics
      (SGAs) has increased significantly in recent years. In this population, SGAs are
      used to treat mood and behavioural disorders although considered 'off-label' or
      not approved for these indications. Metabolic monitoring is the systematic
      physical health assessment of antipsychotic users utilized to detect
      cardiovascular and endocrine side effects and prevent adverse events such as
      weight gain, hyperglycaemia, hyperlipidemia, and arrhythmias. This practice
      ensures safe and efficacious SGA use among children and adolescents. Despite
      widely available, evidence-based metabolic monitoring guidelines, rates of
      monitoring continue to be suboptimal; this exposes children to the unnecessary
      risk of developing poor cardiovascular health and long-term disease. In this
      discursive paper, existing approaches to metabolic monitoring as well as
      challenges to implementing monitoring guidelines in practice are explored. The
      strengths and weaknesses of providing metabolic monitoring across outpatient
      psychiatry, primary care, and collaborative community settings are discussed. We
      suggest that there is no one-size-fits-all solution to improving metabolic
      monitoring care for children and adolescents using SGA in all settings. However,
      we advocate for a pragmatic global approach to enhance safety of children and
      adolescents taking SGAs through collaboration among healthcare disciplines with a
      focus on integrating nurses as champions of metabolic monitoring.

PMID- 29205758
TI  - Transanal endoscopic microsurgery: a New Zealand experience.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEMS) is a proven alternative
      therapy to either radical surgery or endoscopic mucosal resection for rectal
      neoplasms. It has proven benefits with lower morbidity and mortality compared
      with total mesorectal excision, and a lower local recurrence rate when compared
      to endoscopic mucosal techniques. METHODS: A retrospective data collection of
      TEMS procedures performed through Waikato District Health Board, New Zealand,
      from 2010 to 2015 was conducted. Supportive follow-up data were sourced from
      patient records and from local centres around New Zealand. RESULTS: A total of
      137 procedures were performed over the study period, with five being repeat
      procedures. Procedures were mostly performed for benign lesions (66.4%) with an
      overall complication rate of 15.3%, only five of which were Clavien-Dindo grade
      III (3.6%). Our local recurrence rate after resection of benign lesions was 5.1%.
      CONCLUSION: Our data set demonstrates the TEMS procedure to be safe compared to
      radical resection (total mesorectal excision) for sessile rectal lesions. Close
      endoscopic follow-up is recommended, especially for close or incomplete margins.
      Good therapeutic results can be obtained for appropriately selected early
      malignant lesions. TEMS provides better oncological results than endoscopic
      mucosal resection or transanal excision.

PMID- 29205759
TI  - Frailty prevalence and factors associated with the Frailty Phenotype and Frailty
      Index: Findings from the North West Adelaide Health Study.
AB  - OBJECTIVE: To determine the prevalence of frailty and associated factors in the
      North West Adelaide Health Study (2004-2006) using the Frailty Phenotype (FP) and
      Frailty Index (FI). METHODS: Frailty was measured in 909 community-dwelling
      participants aged >=65 years using the FP and FI. RESULTS: The FP classified 18%
      of participants as frail and the FI 48%. The measures were strongly correlated (r
      = 0.76, P < 0.001) and had a kappa agreement of 0.38 for frailty classification,
      with 37% of participants classified as non-frail by the FP being classified as
      frail by the FI. Being older, a current smoker, and having multimorbidity and
      polypharmacy were associated with higher frailty levels by both tools. Female,
      low income, obesity and living alone were associated with the FI. CONCLUSION:
      Frailty prevalence was higher when assessed using the FI. Socioeconomic factors
      and other health determinants contribute to higher frailty levels.

PMID- 29205761
TI  - Cooperative Formation of Long-Range Ordering in Water Ad-layers on Fe3 O4 (111)
      Surfaces.
AB  - The initial stages of water adsorption on magnetite Fe3 O4 (111) surface and the
      atomic structure of the water/oxide interface remain controversial. Herein, we
      provide experimental results obtained by infrared reflection-absorption
      spectroscopy (IRAS) and temperature-programmed desorption (TPD), corroborated by
      density functional theory (DFT) calculations showing that water readily
      dissociates on Fetet sites to form two hydroxo species. These act as an anchor
      for water molecules to form a dimer complex which self-assembles into an ordered
      (2*2) structure. Water ad-layer ordering is rationalized in terms of a
      cooperative effect induced by a hydrogen-bonding network.

PMID- 29205760
TI  - Plasma proprotein-convertase-subtilisin/kexin type 9 (PCSK9) and cardiovascular
      events in type 2 diabetes.
AB  - AIM: To investigate whether plasma concentrations of proprotein-convertase
      subtilisin/kexin type 9 (PCSK9) were associated with cardiovascular (CV) events
      in two cohorts of patients with type 2 diabetes mellitus. METHODS: We considered
      patients from the DIABHYCAR (n = 3137) and the SURDIAGENE (n = 1468) studies.
      Baseline plasma PCSK9 concentration was measured using an immunofluorescence
      assay. In post hoc, but preplanned, analyses we assessed the relationship between
      PCSK9 and the following endpoints: (1) a combined endpoint of major CV events: CV
      death, non-fatal myocardial infarction (MI), stroke and heart failure-related
      hospital admission; (2) a composite of all CV events: MI, stroke, heart failure
      related hospital admission, coronary/peripheral angioplasty or bypass, CV death;
      (3) MI; (4) stroke/transient ischaemic attack (TIA); and (5) CV death. RESULTS:
      In the DIABHYCAR study, plasma PCSK9 tertiles were associated with the incidence
      of MI, all CV events and stroke/TIA (P for trend <.05). In adjusted Cox analysis,
      plasma PCSK9 was associated, independently of classic risk factors, with the
      incidence of major CV events (hazard ratio [HR] for 1-unit increase of log[PCSK9]
      1.28 [95% confidence interval {CI} 1.06-1.55]), the incidence of MI (HR 1.66 [95%
      CI 1.05-2.63]), and the incidence of all CV events (HR 1.22 [95% CI 1.04-1.44]),
      but not with CV death. Plasma PCSK9 was not associated with the incidence of CV
      disease in the participants of the SURDIAGENE study with high CV risk treated
      with statins and insulin. CONCLUSIONS: We found that PCSK9 was inconsistently
      associated with CV events in populations with type 2 diabetes. The association
      may depend on the level of CV risk and the background treatment.

PMID- 29205762
TI  - Crohn's disease involving ileal conduit: a case report.

PMID- 29205763
TI  - A comparison of two pencil beam scanning treatment planning systems for proton
      therapy.
AB  - OBJECTIVE: Analytical dose calculation algorithms for Eclipse and Raystation
      treatment planning systems (TPS), as well as a Raystation Monte Carlo model are
      compared to corresponding measured point doses. METHOD: The TPS were modeled with
      the same beam data acquired during commissioning. Thirty-five typical plans were
      made with each planning system, 31 without range shifter and four with a 5 cm
      range shifter. Point doses in these planes were compared to measured doses.
      RESULTS: The mean percentage difference for all plans between Raystation and
      Eclipse were 1.51 +/- 1.99%. The mean percentage difference for all plans between
      TPS models and measured values are -2.06 +/- 1.48% for Raystation pencil beam
      (PB), -0.59 +/- 1.71% for Eclipse and -1.69 +/- 1.11% for Raystation monte carlo
      (MC). The distribution for the patient plans were similar for Eclipse and
      Raystation MC with a P-value of 0.59 for a two tailed unpaired t-test and
      significantly different from the Raystation PB model with P = 0.0013 between
      Raystation MC and PB. All three models faired markedly better if plans with a 5
      cm range shifter were ignored. Plan comparisons with a 5 cm range shifter give
      differences between Raystation and Eclipse of 3.77 +/- 1.82%. The mean percentage
      difference for 5 cm range shifter plans between TPS models and measured values
      are -3.89 +/- 2.79% for Raystation PB, -0.25 +/- 3.85% for Eclipse and 1.55 +/-
      1.95% for Raystation MC. CONCLUSION: Both Eclipse and Raystation PB TPS are not
      always accurate within +/-3% for a 5 cm range shifters or for small targets. This
      was improved with the Raystation MC model. The point dose calculations of
      Eclipse, Raystation PB, and Raystation MC compare within +/-3% to measured doses
      for the other scenarios tested.

PMID- 29205764
TI  - A case of amoebic colitis following remote historical exposure.

PMID- 29205765
TI  - Slow Magnetic Relaxation and Single-Molecule Toroidal Behaviour in a Family of
      Heptanuclear {CrIII LnIII6 } (Ln=Tb, Ho, Er) Complexes.
AB  - The synthesis, magnetic properties, and theoretical studies of three
      heterometallic {CrIII LnIII6 } (Ln=Tb, Ho, Er) complexes, each containing a metal
      topology consisting of two Ln3 triangles connected via a CrIII linker, are
      reported. The {CrTb6 } and {CrEr6 } analogues display slow relaxation of
      magnetization in a 3000 Oe static magnetic field. Single-crystal measurements
      reveal opening up of the hysteresis loop for {CrTb6 } and {CrHo6 } molecules at
      low temperatures. Ab initio calculations predict toroidal magnetic moments in the
      two Ln3 triangles, which are found to couple, stabilizing a con-rotating
      ferrotoroidal ground state in Tb and Ho examples and extend the possibility of
      observing toroidal behaviour in non DyIII complexes for the first time.

PMID- 29205766
TI  - The bile salt sodium taurocholate induces Campylobacter jejuni outer membrane
      vesicle production and increases OMV-associated proteolytic activity.
AB  - Campylobacter jejuni, the leading cause of bacterial acute gastroenteritis
      worldwide, secretes an arsenal of virulence-associated proteins within outer
      membrane vesicles (OMVs). C. jejuni OMVs contain three serine proteases (HtrA,
      Cj0511, and Cj1365c) that cleave the intestinal epithelial cell (IEC) tight and
      adherens junction proteins occludin and E-cadherin, promoting enhanced C. jejuni
      adhesion to and invasion of IECs. C. jejuni OMVs also induce IECs innate immune
      responses. The bile salt sodium taurocholate (ST) is sensed as a host signal to
      coordinate the activation of virulence-associated genes in the enteric pathogen
      Vibrio cholerae. In this study, the effect of ST on C. jejuni OMVs was
      investigated. Physiological concentrations of ST do not have an inhibitory effect
      on C. jejuni growth until the early stationary phase. Coculture of C. jejuni with
      0.1% or 0.2% (w/v) ST stimulates OMV production, increasing both lipid and
      protein concentrations. C. jejuni ST-OMVs possess increased proteolytic activity
      and exhibit a different protein profile compared to OMVs isolated in the absence
      of ST. ST-OMVs exhibit enhanced cytotoxicity and immunogenicity to T84 IECs and
      enhanced killing of Galleria mellonella larvae. ST increases the level of mRNA
      transcripts of the OMVs-associated serine protease genes and the cdtABC operon
      that encodes the cytolethal distending toxin. Coculture with ST significantly
      enhances the OMVs-induced cleavage of E-cadherin and occludin. C. jejuni OMVs
      also cleave the major endoplasmic reticulum chaperone protein BiP/GRP78 and this
      activity is associated with the Cj1365c protease. These data suggest that C.
      jejuni responds to the presence of physiological concentrations of the bile salt
      ST that increases OMV production and the synthesis of virulence-associated
      factors that are secreted within the OMVs. We propose that these events
      contribute to pathogenesis.

PMID- 29205768
TI  - The applications of regenerative medicine in sinus lift procedures: A systematic
      review.
AB  - BACKGROUND: Findings in regenerative medicine applied to the sinus lift
      procedures. PURPOSE: Evaluate the effectiveness of regenerative medicine in sinus
      lift. MATERIALS AND METHODS: An extensive search for manuscripts were performed
      by using different combinations of keywords and MeSH terms (Pub-med; Embase;
      Scopus; Web of Science Core Collection; Medline; Current Contents Connect;
      Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full
      text selected articles are written in English, Portuguese, Spanish, Italian,
      German, or French, and published until 28 of November 2016. Inclusion criteria
      were: implant osteointegration, radiographic, histologic, and/or
      histomorphometric analysis, clinical studies in humans using of regenerative
      medicine. This systematic review was performed by selecting only randomized
      controlled clinical trials and controlled clinical trials. RESULTS: Eighteen
      published studies (11 CT and 7 RCT) were considered eligible for inclusion in the
      present systematic review. These studies demonstrated considerable variation of
      biomaterial and cell technics used, study design, sinus lift technic, outcomes,
      follow-up, and results. CONCLUSION: Only few studies have demonstrated potential
      of regenerative medicine in sinus lift; further randomized clinical trials are
      needed to achieve more accurate results.

PMID- 29205767
TI  - Atomic mass tag of bismuth-209 for increasing the immunoassay multiplexing
      capacity of mass cytometry.
AB  - Mass cytometry (or CyTOF) is an atomic mass spectrometry-based single-cell
      immunoassay technology, which has provided an increasingly systematic and
      sophisticated view in basic biological and clinical studies. Using elemental
      reporters composed of stable heavy metal isotopes, more than 50 cellular
      parameters are measured simultaneously. However, this current multiplexing does
      not meet the theoretical capability of CyTOF instrumentation with 135 detectable
      channels, primarily due to the limitation of available chemistries for
      conjugating elemental mass tags to affinity reagents. To address this issue, we
      develop herein additional metallic mass tag based on bismuth-209 (209 Bi) for
      efficient conjugation to monoclonal antibody. This enables the use of an
      addtional channel m/z = 209 of CyTOF for single-cell immunoassays. Bismuth has
      nearly the same charge-to-radius ratio as lanthanide elements; thus, bismuth(III)
      cations (209 Bi3+ ) could coordinate with DTPA chelators in the same geometry of
      O- and N-donor groups as that of lanthanide. In this report, the coordination
      chemistry of 209 Bi3+ with DTPA chelators and Maxpar(r) X8 polymers were
      investigated in details. Accordingly, the protocols of conjugating antibody with
      bismuth mass tag were provided. A method based on UV-Vis absorbance at 280 nm of
      209 Bi3+ -labeling DTPA complexes was developed to evaluate the stoichiometric
      ratio of 209 Bi3+ cations to the conjugated antibody. Side-by-side single-cell
      analysis experiments with bismuth- and lanthanide-tagged antibodies were carried
      out to compare the analytical sensitivities. The measurement accuracy of bismuth
      tagged antibody was validated within in vitro assay using primary human natural
      killer cells. Furthermore, bismuth-tagged antibodies were successfully employed
      in cell cycle measurements and high-dimensional phenotyping immunoassays. (c)
      2017 International Society for Advancement of Cytometry.

PMID- 29205769
TI  - Highly dexterous 2-module soft robot for intra-organ navigation in minimally
      invasive surgery.
AB  - BACKGROUND: For some surgical interventions, like the Total Mesorectal Excision
      (TME), traditional laparoscopes lack the flexibility to safely maneuver and reach
      difficult surgical targets. This paper answers this need through designing,
      fabricating and modelling a highly dexterous 2-module soft robot for minimally
      invasive surgery (MIS). METHODS: A soft robotic approach is proposed that uses
      flexible fluidic actuators (FFAs) allowing highly dexterous and inherently safe
      navigation. Dexterity is provided by an optimized design of fluid chambers within
      the robot modules. Safe physical interaction is ensured by fabricating the entire
      structure by soft and compliant elastomers, resulting in a squeezable 2-module
      robot. An inner free lumen/chamber along the central axis serves as a guide of
      flexible endoscopic tools. A constant curvature based inverse kinematics model is
      also proposed, providing insight into the robot capabilities. RESULTS:
      Experimental tests in a surgical scenario using a cadaver model are reported,
      demonstrating the robot advantages over standard systems in a realistic MIS
      environment. CONCLUSION: Simulations and experiments show the efficacy of the
      proposed soft robot.

PMID- 29205770
TI  - Effect of tooth brushing on gloss retention and surface roughness of five bulk
      fill resin composites.
AB  - OBJECTIVES: To determine the effects of tooth brushing on five bulk-fill resin
      based composites (RBCs). METHOD: Ten samples of Filtek Supreme Enamel (control),
      Filtek One Bulk Fill, Tetric EvoCeram Bulk Fill, SonicFill 2, SDR flow+, and
      Admira Fusion X-tra were light cured for 20 seconds using the Valo Grand curing
      light. After 24 hours storage in air at 37 degrees C, specimens were brushed in a
      random order using Colgate OpticWhite dentifrice and a soft toothbrush. Surface
      gloss was measured prior to brushing, after 5,000, 10,000 and 15,000 back and
      forth brushing cycles. Surface roughness was measured after 15,000 brushing
      cycles using atomic force microscopy (AFM) and selected scanning electron
      microscope (SEM) images were taken. The data was examined using ANOVA and pair
      wise comparisons using Scheffe's post-hoc multiple comparison tests (alpha =
      0.05). RESULTS: Surface gloss decreased and the surface roughness increased after
      brushing. Two-way ANOVA showed that both the RBC and the number of brushing
      cycles had a significant negative effect on the gloss. One-way ANOVA showed that
      the RBC had a significant effect on the roughness after 15,000 brushing cycles.
      For both gloss and roughness, brushing had the least effect on the nano-filled
      control and nano-filled bulk-fill RBC, and the greatest negative effect on Admira
      Fusion X-tra. The SEM images provided visual agreement. There was an excellent
      linear correlation (R2  = 0.98) between the logarithm of the gloss and roughness.
      CONCLUSION: After brushing, the bulk-fill RBCs were all rougher than the control
      nano-filled RBC. The nano-filled bulk-fill RBC was the least affected by
      brushing. CLINICAL SIGNIFICANCE: Bulk-fill RBCs lose their gloss faster and
      become rougher than the nanofilled conventional RBC, Filtek Supreme Ultra. The
      nanofilled bulk-fill RBC was the least affected by tooth brushing.

PMID- 29205771
TI  - Homoeologous exchange is a major cause of gene presence/absence variation in the
      amphidiploid Brassica napus.
AB  - Homoeologous exchanges (HEs) have been shown to generate novel gene combinations
      and phenotypes in a range of polyploid species. Gene presence/absence variation
      (PAV) is also a major contributor to genetic diversity. In this study, we show
      that there is an association between these two events, particularly in recent
      Brassica napus synthetic accessions, and that these represent a novel source of
      genetic diversity, which can be captured for the improvement of this important
      crop species. By assembling the pangenome of B. napus, we show that 38% of the
      genes display PAV behaviour, with some of these variable genes predicted to be
      involved in important agronomic traits including flowering time, disease
      resistance, acyl lipid metabolism and glucosinolate metabolism. This study is a
      first and provides a detailed characterization of the association between HEs and
      PAVs in B. napus at the pangenome level.

PMID- 29205772
TI  - The Exploitation of Enzymatically-Derived cis-1,2-Dihydrocatechols and Related
      Compounds in the Synthesis of Biologically Active Natural Products.
AB  - The title compounds of the general form 1 can be produced at large scale and in
      essentially enantiomerically pure form (when X?H) through the whole cell
      biotransformation of the corresponding aromatic. The "dense" and varied
      functionality associated with these metabolites mean that they have become
      increasingly useful chirons for the total synthesis of a range of natural product
      types. This personal account details the outcomes of a nearly three-decade long
      campaign within our group to exploit these compounds in the synthesis of a
      diverse range of small molecule natural product targets. The work is subdivided
      according to the key transformation(s) employed in each synthesis. The
      development of newer chirons that "complement" the utility of the cis-1,2
      dihydrocatechols are also described.

PMID- 29205774
TI  - Comparison of glucose-lowering agents after dual therapy failure in type 2
      diabetes: A systematic review and network meta-analysis of randomized controlled
      trials.
AB  - AIMS: To assess the evidence supporting the choice of third-line agents in adults
      with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We searched
      randomized controlled trials (RCTs) published between January 2000 and July 2017
      that reported data on cardiometabolic outcomes and hypoglycaemia for glucose
      lowering agents added to metformin-based dual treatments. Data were stratified by
      background therapy and RCT duration, and synthesized, when possible, with network
      meta-analyses. RESULTS: A total of 43 RCTs (16 590 participants) were included,
      with metformin combined with: sulphonylureas (SUs) in 20 RCTs; thiazolidinediones
      (TZDs) in 10; basal or rapid-acting insulin in 6; dipeptidyl peptidase-4 (DPP-4)
      inhibitors in 3; glucagon-like peptide-1 receptor agonists (GLP-1RAs) in 2; and
      sodium-glucose co-transporter-2 (SGLT-2) inhibitors in 2. When added to metformin
      and SUs, after 24 to 36 weeks, rapid-acting insulin resulted in the largest
      reduction in glycated haemoglobin (HbA1c; 1.6% vs placebo), followed by GLP-1RAs
      (1.0%), basal insulin (0.8%) and SGLT-2 inhibitors (0.7%), with no difference
      between GLP-1RAs and SGLT-2 inhibitors; body weight increased with insulin
      treatment (~3 kg vs placebo), while the greatest reduction was observed for SGLT
      2 inhibitors compared with all other therapies. Limited data for hypoglycaemia
      indicated a similar risk for SGLT-2 inhibitors and GLP-1RAs. Results for third
      line agents added to metformin and TZDs were comparable, showing similar HbA1c
      reduction and risk of hypoglycaemia between SGLT-2 inhibitors and GLP-1RAs, and a
      slightly greater reduction in body weight with SGLT-2 inhibitors vs GLP-1RAs.
      Data for 52 to 54 weeks were more limited: added to metformin and a SU, TZDs, GLP
      1RAs or SGLT-2 inhibitors reduced HbA1c to a similar extent but had different
      effects on body weight (7 kg and 5 kg more with TZDs vs SGLT-2 inhibitors and GLP
      1RAs, respectively; 2 kg less when comparing SGLT-2 inhibitors with GLP-1RAs).
      Formal analyses could not be performed for any other dual therapy failure
      combinations because of the small number of available RCTs. CONCLUSIONS: Moderate
      quality evidence supports the choice of a third-line agent only in patients on
      metformin combined with a SU or a TZD, with SGLT-2 inhibitors performing
      generally better than other drugs. In suggesting third-line agents, future
      guidelines should recognize the widely differing evidence on the various dual
      therapy failures.

PMID- 29205775
TI  - Donor-derived, metastatic urothelial cancer after kidney transplantation
      associated with a potentially oncogenic BK polyomavirus.
AB  - BK polyomavirus has been linked to urothelial carcinoma in immunosuppressed
      patients. Here, we performed comprehensive genomic analysis of a BK polyomavirus
      associated, metachronous, multifocal and metastatic micropapillary urothelial
      cancer in a kidney transplant recipient. Dissecting cancer heterogeneity by
      sorting technologies prior to array-comparative genomic hybridization followed by
      short tandem repeat analysis revealed that the metastatic urothelial cancer was
      of donor origin (4-year-old male). The top 50 cancer-associated genes showed no
      key driver mutations as assessed by next-generation sequencing. Whole genome
      sequencing and BK polyomavirus-specific amplification provided evidence for
      episomal and subgenomic chromosomally integrated BK polyomavirus genomes, which
      carried the same unique 17-bp deletion signature in the viral non-coding control
      region (NCCR). Whereas no role in oncogenesis could be attributed to the host
      gene integration in chromosome 1, the 17-bp deletion in the NCCR increased early
      viral gene expression, but decreased viral replication capacity. Consequently,
      urothelial cells were exposed to high levels of the transforming BK polyomavirus
      early proteins large tumour antigen and small tumour antigen from episomal and
      integrated gene expression. Surgery combined with discontinuation of
      immunosuppression resulted in complete remission, but sacrificed the renal
      transplant. Thus, this report links, for the first time, BK polyomavirus NCCR
      rearrangements with oncogenic transformation in urothelial cancer in
      immunosuppressed patients. Copyright (c) 2017 Pathological Society of Great
      Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29205776
TI  - The Graduating European Dentist: Contemporaneous Methods of Teaching, Learning
      and Assessment in Dental Undergraduate Education.
AB  - It is often the case that good teachers just "intuitively" know how to teach.
      Whilst that may be true, there is now a greater need to understand the various
      processes that underpin both the ways in which a curriculum is delivered, and the
      way in which the students engage with learning; curricula need to be designed to
      meet the changing needs of our new graduates, providing new, and robust learning
      opportunities, and be communicated effectively to both staff and students. The
      aim of this document is to draw together robust and contemporaneous methods of
      teaching, learning and assessment that help to overcome some of the more
      traditional barriers within dental undergraduate programmes. The methods have
      been chosen to map specifically to The Graduating European Dentist, and should be
      considered in parallel with the benchmarking process that educators and
      institutions employ locally.

PMID- 29205777
TI  - Preface.

PMID- 29205778
TI  - The Graduating European Dentist-Domain II: Safe and Effective Clinical Practice.
AB  - This position paper outlines the areas of competence and learning outcomes of
      "The Graduating European Dentist" that specifically relate to Safe and Effective
      Clinical Practice. Dentists are required to ensure that they are capable of
      providing appropriate care for their patients, whilst also effectively managing
      and leading the wider clinical team. The care that is provided should align to a
      contemporaneous evidence base wherever possible, and the quality of care and the
      management systems that underpin it should be regularly audited and improved.

PMID- 29205773
TI  - Treponema denticola increases MMP-2 expression and activation in the periodontium
      via reversible DNA and histone modifications.
AB  - Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate
      destruction of extracellular matrices and supporting alveolar bone in
      periodontitis. The Treponema denticola dentilisin protease induces MMP-2
      expression and activation in periodontal ligament (PDL) cells, and dentilisin
      mediated activation of pro-MMP-2 is required for cellular fibronectin
      degradation. Here, we report that T. denticola regulates MMP-2 expression through
      epigenetic modifications in the periodontium. PDL cells were treated with
      epigenetic enzyme inhibitors before or after T. denticola challenge. Fibronectin
      fragmentation, MMP-2 expression, and activation were assessed by immunoblot,
      zymography, and qRT-PCR, respectively. Chromatin modification enzyme expression
      in T. denticola-challenged PDL cells and periodontal tissues were evaluated using
      gene arrays. Several classes of epigenetic enzymes showed significant alterations
      in transcription in diseased tissue and T. denticola-challenged PDL cells. T.
      denticola-mediated MMP-2 expression and activation were significantly reduced in
      PDL cells treated with inhibitors of aurora kinases and histone deacetylases. In
      contrast, DNA methyltransferase inhibitors had little effect, and inhibitors of
      histone acetyltransferases, methyltransferases, and demethylases exacerbated T.
      denticola-mediated MMP-2 expression and activation. Chronic epigenetic changes in
      periodontal tissues mediated by T. denticola or other oral microbes may
      contribute to the limited success of conventional treatment of chronic
      periodontitis and may be amenable to therapeutic reversal.

PMID- 29205779
TI  - The Graduating European Dentist-Domain IV: Dentistry in Society.
AB  - This position paper outlines the areas of competence and learning outcomes of
      "The Graduating European Dentist" that specifically relates to Dentistry in
      Society. In addition to treating individual patients, a Dentist must be able to
      focus on promoting health, monitoring interventions and implementing effective
      strategies of care at community and population levels. This necessarily involves
      understanding population demography and health trends, engaging with health
      policy and promoting health. A Dentist must also understand population demography
      and health trends, in the context of the healthcare system within which they
      work.

PMID- 29205780
TI  - The Graduating European Dentist-Domain I: Professionalism.
AB  - This position paper outlines the areas of competence and learning outcomes of
      "The Graduating European Dentist" that specifically relate to Professionalism.
      Professionalism is a commitment to a set of values, behaviours and relationships,
      which underpin the trust that the public hold in dental care professionals.
      Shortcomings within this domain are often responsible for patient
      dissatisfaction, concern and complaint-and emphasis is placed on the importance
      of embedding these values from an early stage within the curriculum.

PMID- 29205781
TI  - The Graduating European Dentist-Domain III: Patient-Centred Care.
AB  - This position paper outlines the areas of competence and learning outcomes of
      "The Graduating European Dentist" that specifically relate to patient-centred
      care. This approach is becoming increasingly prominent within the literature and
      within policy documents. Whilst working to an evidence base is critical, dentists
      must also be aware of the scientific basis that underpins the treatment they
      provide. The evaluation process, which supports treatment planning, also requires
      dentists to be able to listen, collate, and record pertinent information
      effectively. In addition, the ability to account for a patient's social, cultural
      and linguistic needs (cultural competence) will result in a practitioner who is
      able to treatment plan for patient-centred care.

PMID- 29205782
TI  - The Graduating European Dentist: A New Undergraduate Curriculum Framework.
AB  - With "The Graduating European Dentist", ADEE provides a new approach that
      reflects best academic practice for European undergraduate dental education. The
      new suite of documents sees increased emphasis on important curriculum components
      such as patient safety, working as a team and patient-centred care. There is also
      an increased emphasis on teaching excellence, student satisfaction and student
      preparedness and support. Guidance relating to methods of teaching and learning,
      and assessment (educational measurement), is also provided. It is anticipated
      that this new format will further increase accessibility and utility for
      educators, institutions, societies and regulators, across the sector.

PMID- 29205783
TI  - Transanal minimally invasive full-thickness anterior middle rectum polyp
      resection - video vignette.
AB  - Rectal preservation is gaining popularity in the surgical treatment of
      degenerated rectal polyps or early rectal cancer (1,2). Tis/T1 rectal lesions can
      be safely treated without chemoradiation (3). Treatment by transanal minimally
      invasive surgery (TAMIS) offers more advantages than endoscopic submucosal
      dissection (ESD) (4). The authors report a 60 year-old woman who underwent TAMIS
      for a large polyp located anteriorly in the middle 1/3 of the rectum, 7 cm from
      the dentate line and staged preoperatively as uTisN0M0. This article is protected
      by copyright. All rights reserved.

PMID- 29205784
TI  - Thoracic epidural analgesia in donor hepatectomy: An analysis.
AB  - The purpose of this study is to analyze whether supplementation of general
      anesthesia (GA) with thoracic epidural analgesia (TEA) for right lobe donor
      hepatectomy is a safe modality of pain relief in terms of changes in
      postoperative coagulation profile, incidence of epidural catheter-related
      complications, and timing of removal of epidural catheter. Retrospective analysis
      of the record of 104 patients who received TEA for right lobe donor hepatectomy
      was done. Platelet count, international normalized ratio, alanine
      aminotransferase, and aspartate aminotransferase were recorded postoperatively
      until the removal of the epidural catheter. The day of removal of the epidural
      catheter and visual analogue scale (VAS) scores were also recorded. Any
      complication encountered was documented. Intraoperatively, central venous
      pressure (CVP), hemodynamic variables, and volume of intravenous fluids infused
      were also noted. Statistical analysis was performed by using SPSS statistical
      package, version 17.0 (SPSS Inc. Chicago, IL). Continuous variables were
      presented as mean +/- standard deviation. A total of 90% of patients had mean VAS
      scores between 1 and 4 in the postoperative period between days 1 and 5. None of
      the patients had a VAS score above 5. Although changes in coagulation status were
      encountered in all patients in the postoperative period, these changes were
      transient and did not persist beyond postoperative day (POD) 5. There was no
      delay in removal of the epidural catheter, and the majority of patients had the
      catheter removed by POD 4. There was no incidence of epidural hematoma. Aside
      from good intraoperative and postoperative analgesia, TEA in combination with
      balanced GA and fluid restriction enabled maintenance of low CVP and prevention
      of hepatic congestion. In conclusion, vigilant use of TEA appears to be safe
      during donor hepatectomy. Living liver donors should not be denied efficient
      analgesia for the fear of complications. Liver Transplantation 24 214-221 2018
      AASLD.

PMID- 29205785
TI  - Plant Polyphenols Stimulate Adhesion to Intestinal Mucosa and Induce Proteome
      Changes in the Probiotic Lactobacillus acidophilus NCFM.
AB  - SCOPE: Plant phenolics, known to exert beneficial effects on human health, were
      supplemented to cultures of the probiotic bacterium Lactobacillus acidophilus
      NCFM (NCFM) to assess their effect on its adhesive capacity and the abundancy of
      individual proteins. METHODS AND RESULTS: The presence of resveratrol and ferulic
      acid during bacterial growth stimulated adhesion of NCFM to mucin and human
      intestinal HT-29 cells, while tannic acid improved adhesion only to HT-29 cells
      and caffeic acid had very modest effect overall. Some dosage dependence was found
      for the four phenolics supplemented at 100, 250, and 500 MUg mL-1 to the
      cultures. Notably, 500 MUg mL-1 ferulic acid only stimulated adhesion to mucin.
      Analyses of differential whole-cell as well as surface proteomes revealed
      relative abundancy changes for a total of 27 and 22 NCFM proteins, respectively.
      These changes include enzymes acting in metabolic pathways, such as glycolysis,
      nucleotide metabolism, and stress response, as well as known moonlighting or
      surface-associated proteins. CONCLUSION: The five plant phenolics found in
      various foods stimulate the adhesive capacity of NCFM in diverse ways and elicit
      relative abundancy changes of specific proteins, providing molecular level
      insight into the mechanism of the putative beneficial effects of the polyphenols.

PMID- 29205786
TI  - Pharmacokinetics and tolerability of semaglutide in people with hepatic
      impairment.
AB  - AIMS: To investigate whether the pharmacokinetic characteristics of semaglutide
      were altered in people with hepatic impairment, assessed using Child-Pugh
      criteria, vs those with normal hepatic function. METHODS: In this multicentre,
      open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID
      NCT02210871), four groups of participants with normal hepatic function (n = 19)
      or mild (n = 8), moderate (n = 10) or severe (n = 7) hepatic impairment received
      a single, subcutaneous dose of 0.5 mg semaglutide. Semaglutide plasma
      concentrations were assessed frequently for 35 days after dosing. The primary
      endpoint was area under the semaglutide plasma concentration-time curve from time
      zero to infinity (AUC0-infinity ). No effect of hepatic impairment was declared
      if the 90% confidence interval (CI) for the between-group ratio (hepatic
      impairment/normal function) was within the interval 0.70 to 1.43. RESULTS:
      Semaglutide exposure was similar across all groups, with AUC0-infinity treatment
      ratios for mild impairment/normal function of 0.95 (90% CI 0.77, 1.16), moderate
      impairment/normal function 1.02 (90% CI 0.93, 1.12), and severe impairment/normal
      function 0.97 (90% CI 0.84, 1.12). The maximum plasma semaglutide concentration
      (Cmax ) did not appear to be influenced by hepatic function, with mild
      impairment/normal function treatment ratios of 0.99 (90% CI 0.80, 1.23), moderate
      impairment/normal function 1.02 (90% CI 0.88, 1.18) and severe impairment/normal
      function 1.15 (90% CI 0.89, 1.48; sensitivity analysis excluding one extreme
      semaglutide concentration: 1.05 [90% CI 0.88, 1.25]). In all, 10 participants
      reported 12 mild or moderate non-serious adverse events. No unexpected safety or
      tolerability issues were observed. CONCLUSIONS: Semaglutide exposure did not
      appear to be affected by hepatic impairment, suggesting that dose adjustment may
      not be necessary in patients with hepatic impairment. Semaglutide was well
      tolerated and there were no unexpected safety issues.

PMID- 29205787
TI  - System for CT-guided needle placement in the thorax and abdomen: A design for
      clinical acceptability, applicability and usability.
AB  - BACKGROUND: Various systems exist for CT-guided needle placement in the thorax
      and abdomen, but widespread adoption is lacking. The goal of this work is to
      develop a system for precise needle placement with a design focus on clinical
      acceptability, applicability and usability. METHODS: A system was outlined
      incorporating a needle guide on a mechanism with a remote centre of motion,
      manually placeable around the patient at the desired entry point and lockable by
      push-button to the CT table. System and patient are scanned for system-to-CT
      registration and target specification. The needle guide is automatically aimed at
      the target, for manual needle insertion to specified depth. RESULTS: A fully
      functional prototype was realized, achieving 1.2+/-0.6 mm placement error at
      79.0+/-8.4 mm depth and 2.1+/-0.7 mm at 156.0+/-6.9 mm for 2*12 in- and out-of
      plane punctures in a gelatin phantom. CONCLUSIONS: The system enables precise
      needle placement in a single insertion and is ready for its first clinical
      deployment.

PMID- 29205788
TI  - Normal variation of bone marrow B-cell precursors according to age - reference
      ranges for studies in myelodysplastic syndromes in Brazil.
AB  - BACKGROUND: Normal B lymphoid maturation occurs in bone marrow (BM) throughout
      life, but immature B-cell progenitors (BCPs) are more numerous in children than
      in adults. To assess the normal values according to age became important as BCPs
      are decreased in myelodysplastic syndromes and have been considered an important
      diagnostic and prognostic feature in these clonal disorders. METHODS: in a
      multicenter retrospective study from the Brazilian Group of Flow Cytometry we
      analyzed the variation of BCPs in normal BM according to age and technical
      peculiarities of each laboratory. We analysed of 45 BM donors and 89 cases
      examined for elucidation of transitory reactive cytopenias presenting a normal BM
      immunophenotyping. BCPs were enumerated as CD19+ /CD34+ /CD45dim /CD10+ cells
      (panel 1) or CD19+ /CD34+ /CD45dim cells (panel 2) among the total nucleated non
      erythroid cells and as percentage of CD34+ cells. RESULTS: we included 134 cases.
      Panel 1 was applied in 88 cases and panel 2 was used in 46. Age range: 10 months
      to 89 years. In a multiple regression, % BCPs/total nucleated cells was an
      exponential function of age. Age explained alone 49.4% of the variance, while
      'panel used' explained 1.8% and 'laboratory' explained 0.7%. Age explained only
      24.9% of the variance of BCPs/CD34+ cells. CONCLUSIONS: in normal individuals, BM
      B-cell precursors varied mainly according to age, but were also dependent on
      technical peculiarities of operators and equipments. Analysis by phenotype and as
      percentage of total nucleated cells was more accurate and less susceptible to
      variation than evaluating % BCPs/total CD34+ cells. (c) 2017 International
      Clinical Cytometry Society.

PMID- 29205789
TI  - Modified jailed balloon technique for bifurcation lesions.
AB  - OBJECTIVES: We propose a new systematic approach in bifurcation lesions, modified
      jailed balloon technique (M-JBT), and report the first clinical experience.
      BACKGROUND: Side branch occlusion brings with a serious complication and occurs
      in more than 7.0% of cases during bifurcation stenting. METHODS: A jailed balloon
      (JB) is introduced into the side branch (SB), while a stent is placed in the main
      branch (MB) as crossing SB. The size of the JB is half of the MB stent size.
      While the proximal end of JB attaching to MB stent, both stent and JB are
      simultaneously inflated with same pressure. JB is removed and then guidewires are
      recrossed. Kissing balloon dilatation (KBD) and/or T and protrusion (TAP)
      stenting are applied as needed. RESULTS: Between February 2015 and February 2016,
      233 patients (254 bifurcation lesions including 54 left main trunk disease)
      underwent percutaneous coronary intervention (PCI) using this technique.
      Procedure success was achieved in all cases. KBD was performed for 183 lesions
      and TAP stenting was employed for 31 lesions. Occlusion of SV was not observed in
      any of the patients. Bench test confirmed less deformity of MB stent in M-JBT
      compared with conventional-JBT. CONCLUSIONS: This is the first report for
      clinical experiences by using modified jailed balloon technique. This novel M-JBT
      is safe and effective in the preservation of SB patency during bifurcation
      stenting.

PMID- 29205790
TI  - A Molecular Approach to Manganese Nitride Acting as a High Performance
      Electrocatalyst in the Oxygen Evolution Reaction.
AB  - The scalable synthesis of phase-pure crystalline manganese nitride (Mn3 N2 ) from
      a molecular precursor is reported. It acts as a superiorly active and durable
      electrocatalyst in the oxygen evolution reaction (OER) from water under alkaline
      conditions. While electrophoretically deposited Mn3 N2 on fluorine tin oxide
      (FTO) requires an overpotential of 390 mV, the latter is substantially decreased
      to merely 270 mV on nickel foam (NF) at a current density of 10 mA cm-2 with a
      durability of weeks. The high performance of this material is due to the rapid
      transformation of manganese sites at the surface of Mn3 N2 into an amorphous
      active MnOx overlayer under operation conditions intimately connected with
      metallic Mn3 N2 , which increases the charge transfer from the active catalyst
      surface to the electrode substrates and thus outperforms the electrocatalytic
      activity in comparison to solely MnOx -based OER catalysts.

PMID- 29205791
TI  - Observation of Resistive Switching Behavior in Crossbar Core-Shell Ni/NiO
      Nanowires Memristor.
AB  - The crossbar structure of resistive random access memory (RRAM) is the most
      promising technology for the development of ultrahigh-density devices for future
      nonvolatile memory. However, only a few studies have focused on the switching
      phenomenon of crossbar RRAM in detail. The main purpose of this study is to
      understand the formation and disruption of the conductive filament occurring at
      the crossbar center by real-time transmission electron microscope observation.
      Core-shell Ni/NiO nanowires are utilized to form a cross-structure, which
      restrict the position of the conductive filament to the crosscenter. A
      significant morphological change can be observed near the crossbar center, which
      results from the out-diffusion and backfill of oxygen ions. Energy dispersive
      spectroscopy and electron energy loss spectroscopy demonstrate that the movement
      of the oxygen ions leads to the evolution of the conductive filament, followed by
      redox reactions. Moreover, the distinct reliability of the crossbar device is
      measured via ex situ experiments. In this work, the switching mechanism of the
      crossbar core-shell nanowire structure is beneficial to overcome the problem of
      nanoscale minimization. The experimental method shows high potential to fabricate
      high-density RRAM devices, which can be applied to 3D stacked package technology
      and neuromorphic computing systems.

PMID- 29205792
TI  - Magnetotaxis Enables Magnetotactic Bacteria to Navigate in Flow.
AB  - Magnetotactic bacteria (MTB) play an important role in Earth's biogeochemical
      cycles by transporting minerals in aquatic ecosystems, and have shown promise for
      controlled transport of microscale objects in flow conditions. However, how MTB
      traverse complex flow environments is not clear. Here, using microfluidics and
      high-speed imaging, it is revealed that magnetotaxis enables directed motion of
      Magnetospirillum magneticum over long distances in flow velocities ranging from 2
      to 1260 um s-1 , corresponding to shear rates ranging from 0.2 to 142 s-1 -a
      range relevant to both aquatic environments and biomedical applications. The
      ability of MTB to overcome a current is influenced by the flow, the magnetic
      field, and their relative orientation. MTB can overcome 2.3-fold higher flow
      velocities when directed to swim perpendicular to the flow as compared to
      upstream, as the latter orientation induces higher drag. The results indicate a
      threshold drag of 9.5 pN, corresponding to a flow velocity of 550 um s-1 , where
      magnetotaxis enables MTB to overcome counterdirectional flow. These findings
      bring new insights into the interactions of MTB with complex flow environments
      relevant to aquatic ecosystems, while suggesting opportunities for in vivo
      applications of MTB in microbiorobotics and targeted drug delivery.

PMID- 29205793
TI  - Duodenal graft complications requiring duodenectomy after pancreas and pancreas
      kidney transplantation.
AB  - Duodenal graft complications are poorly reported complications of pancreas
      transplantation that can result in graft loss. Excluding patients with early
      graft failure, after a median follow-up period of 126 months (range 23-198)
      duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients
      were insulin-independent at the time of diagnosis. Reasons for duodenectomy
      included delayed duodenal graft perforation (n = 10, 71.5%) and refractory
      duodenal graft bleeding (n = 4, 28.5%). In patients with duodenal graft bleeding,
      a total duodenectomy was performed. In patients with duodenal graft perforation,
      preservation of a duodenal segment was possible in five patients but completion
      duodenectomy was necessary in one patient. After total duodenectomy, immediate
      enteric duct drainage was feasible in seven patients. In two patients, a
      pancreaticocutaneous fistula was created that was subsequently converted to
      enteric drainage in one patient. In the other patient, enteric fistulization
      occurred as a consequence of silent pressure perforation of the draining catheter
      on the ascending colon. After a mean follow-up period of 52 months (21-125), all
      patients were alive, well, and insulin-independent. An aggressive and timely
      surgical approach may permit graft rescue in patients with severe duodenal graft
      complications occurring after pancreas transplantation. Generalization of these
      results remains to be established.

PMID- 29205794
TI  - Biallelic mutations in LARS2 can cause Perrault syndrome type 2 with neurologic
      symptoms.
AB  - Perrault syndrome represents a genetically heterogeneous disorder characterized
      by sensorineural hearing loss in males and females and ovarian dysfunction in
      females. Causative genes include HARS2, HSD17B4, CLPP, C10orf2, and LARS2. Some
      patients with Perrault syndrome exhibit neurologic features including learning
      disability, cerebellar ataxia, and peripheral neuropathy and are classified as
      type 2 and are clinically separate from those without neurological symptoms other
      than a hearing loss (type 1). To date, all reported patients with LARS2 mutations
      (15 patients in 8 families) have been classified as type 1. Here, we report
      female siblings with biallelic mutations in LARS2, p.Glu294Lys, and p.Thr519Met,
      who were classified as type 2. The proposita developed progressive sensorineural
      hearing loss at 18 months and pervasive developmental disorder at 8 years, with
      repetitive behavior, insistence on sameness, attention deficit, tic,
      irritability, and an ataxic gait. At age 15 years, she was diagnosed as having
      primary amenorrhea with elevated FSH and LH and a decreased estradiol; ultrasound
      and magnetic resonance imaging examinations revealed a small uterus and no
      detectable ovaries. The proposita's younger sister presented with neonatal
      sensorineural hearing loss and a mild delay in motor and speech development. She
      was diagnosed as having primary amenorrhea with endocrinologic and radiographic
      findings that were comparable to those of her sister. She had difficulty with
      reading comprehension, and had trouble with open-ended test questions at 12 years
      of age. We concluded that Perrault syndrome patients with LARS2 mutations are at
      risk for neurologic problems, despite previous notions otherwise.

PMID- 29205795
TI  - Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for
      Synergism of Photothermal Therapy and Chemotherapy.
AB  - Mitochondrial-targeting therapy is an emerging strategy for enhanced cancer
      treatment. In the present study, a multistage targeting strategy using
      doxorubicin-loaded magnetic composite nanoparticles is developed for enhanced
      efficacy of photothermal and chemical therapy. The nanoparticles with a core
      shell-SS-shell architecture are composed of a core of Fe3 O4 colloidal
      nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with
      triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol)
      linked to the PDA by disulfide bonds. The magnetic core can increase the
      accumulation of nanoparticles at the tumor site for the first stage of tumor
      tissue targeting. After the nanoparticles enter the tumor cells, the second stage
      of mitochondrial targeting is realized as the mPEG shell is detached from the
      nanoparticles by redox responsiveness to expose the TPP. Using near-infrared
      light irradiation at the tumor site, a photothermal effect is generated from the
      PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane
      potential. Simultaneously, the loaded doxorubicin can rapidly enter the
      mitochondria and subsequently damage the mitochondrial DNA, resulting in cell
      apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting
      the mitochondria significantly enhances the cancer treatment.

PMID- 29205796
TI  - Nanoarchitectonics from Molecular Units to Living-Creature-Like Motifs.
AB  - Important points for the fabrication of functional materials are the creation of
      nanoscale/molecular-scale units and architecting them into functional materials
      and systems. Recently, a new conceptual paradigm, nanoarchitectonics, has been
      proposed to combine nanotechnology and other methodologies including
      supramolecular chemistry, self-assembly and self-organization to satisfy major
      features of nanoscience and promote the creation of functional materials and
      systems. In this account article, our recent research results in materials
      development based on the nanoarchitectonics concept are summarized in two
      stories, (i) nanoarchitectonics from fullerenes as the simplest nano-units and
      (ii) dimension-dependent nanoarchitectonics from various structural units. The
      former demonstrates creativity of the nanoarchitectonics concept only with simple
      construction stuffs on materials fabrications, and a wide range of material
      applicability for the nanoarchitectonics strategy is realized in the latter ones.

PMID- 29205797
TI  - Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current
      status, and opportunities.
AB  - A variety of surgical and other local-regional approaches to the management of
      hepatocellular carcinoma (HCC) are in clinical use. External beam radiation
      therapy is a relative newcomer to the portfolio of treatment options. Advances in
      planning and delivery of radiation therapy, developing in parallel with and
      inspiring changing paradigms of tumor management in the field of radiation
      oncology, have led to growing interest in radiation therapy as a viable treatment
      option for HCC as well as other liver tumors. In this review, we discuss these
      advances, current trends in liver radiotherapy, as well as avenues of future
      clinical and basic research. Liver Transplantation 24 420-427 2018 AASLD.

PMID- 29205798
TI  - Carotid-cavernous fistula after endovascular intervention for chronic carotid
      artery total occlusion.
AB  - BACKGROUND AND PURPOSE: In addition to head trauma and cranial surgery,
      endovascular intervention for chronic carotid artery occlusion (CAO) may also
      result in carotid-cavernous fistula (CCF). The management and prognosis of
      iatrogenic CCF during CAO recanalization have never been well described and
      discussed in the literature. MATERIALS AND METHODS: We conducted a retrospective
      analysis for CAO recanalization attempts in National Taiwan University Hospital
      and affiliated hospitals. Incidence and presentation, demographic and
      angiographic variables, and clinical follow-up of the development of iatrogenic
      CCF were carefully reviewed. RESULTS: A total of 138 consecutive de novo CAO
      endovascular recanalization attempts were reviewed. The technical success rate
      was 61.6% (85/138). Complication rate, including death, stroke, and intracranial
      or sub-arachnoid hemorrhage (ICH or SAH) was 4.3% (6/138). CCF developed in 11
      patients (8.0%), and none resulted in death, stroke, or ICH/SAH within 30 days.
      Female gender and distal carotid artery reconstitution at communicating or
      ophthalmic segments were associated with development of CCF. Imaging follow-ups
      were performed in eight patients and none showed persistent CCF. CONCLUSION: CCF
      may develop during chronic CAO endovascular recanalization attempts. It is
      usually self-limited and can be managed conservatively.

PMID- 29205799
TI  - Interface Engineering with MoS2 -Pd Nanoparticles Hybrid Structure for a Low
      Voltage Resistive Switching Memory.
AB  - Metal oxide-based resistive random access memory (RRAM) has attracted a lot of
      attention for its scalability, temperature robustness, and potential to achieve
      machine learning. However, a thick oxide layer results in relatively high program
      voltage while a thin one causes large leakage current and a small window. Owing
      to these fundamental limitations, by optimizing the oxide layer itself a novel
      interface engineering idea is proposed to reduce the programming voltage,
      increase the uniformity and on/off ratio. According to this idea, a molybdenum
      disulfide (MoS2 )-palladium nanoparticles hybrid structure is used to engineer
      the oxide/electrode interface of hafnium oxide (HfOx )-based RRAM. Through its
      interface engineering, the set voltage can be greatly lowered (from -3.5 to -0.8
      V) with better uniformity under a relatively thick HfOx layer (~15 nm), and a 30
      times improvement of the memory window can be obtained. Moreover, due to the
      atomic thickness of MoS2 film and high transmittance of ITO, the proposed RRAM
      exhibits high transparency in visible light. As the proposed interface
      engineering RRAM exhibits good transparency, low SET voltage, and a large
      resistive switching window, it has huge potential in data storage in transparent
      circuits and wearable electronics with relatively low supply voltage.

PMID- 29205800
TI  - Cucurbitacin B acts a potential insect growth regulator by antagonizing 20
      hydroxyecdysone activity.
AB  - BACKGROUND: 20-Hydroxyecdysone (20E), a crucial insect steroid hormone, can bind
      to its cognate nuclear receptor composed of ecdysone receptor (EcR) and
      ultraspiracle (USP) to activate expression of 20E-response genes, enabling
      subsequent metamorphosis. In this study, we tried to find out which steroid-like
      compounds can block insect metamorphosis effectively and provide useful
      information for biopesticide study. For this purpose, we screened 126 steroid
      like compounds for possible 20E antagonists using a dual-luciferase reporter
      assay with Drosophila melanogaster Kc and Bombyx mori Bm12 cells. RESULTS: Among
      126 steroid-like compounds, three cucurbitacins (CucB, D and E) were identified
      as 20E antagonists in both Kc and Bm12 cells. Notably, CucB caused significant
      molting defects and mortality in both B. mori and D. melanogaster larvae, and
      dramatically hindered larval growth of Helicoverpa armigera by its anti-feeding
      activity. CONCLUSION: In vivo and in vitro experiments demonstrate that CucB acts
      as a potential insect growth regulator by antagonizing 20E activity and thus
      blocking molting and metamorphosis induced by 20E signaling. (c) 2017 Society of
      Chemical Industry.

PMID- 29205801
TI  - Acute Splenic Sequestration Crisis After Red Blood Cell Exchange for Acute Chest
      Syndrome in an Adult With Sickle beta-Thalassemia: What Went Wrong?

PMID- 29205803
TI  - Septal reduction therapy using nonalcohol agent in hypertrophic obstructive
      cardiomyopathy: Single center experience.
AB  - AIMS: Percutaneous septal reduction therapy by either alcohol or nonalcohol
      agents is an alternative approach to surgery in drug-refractory symptomatic
      patients with hypertrophic obstructive cardiomyopathy (HOCM). Nonalcohol agents
      have some advantages and disadvantages over alcohol during the procedure.
      Nowadays, a novel non-alcohol agent, named as Ethylene-vinyl alcohol (EVOH)
      copolymer (Onyx(r) and Squid(r) ), is used during septal ablation. Thus, in this
      study, we aimed to evaluate both acute and long-term efficacy and safety profile
      of EVOH during septal ablation in HOCM. METHODS AND RESULTS: A total of 25
      patients (52% female; mean age: 55.8 +/- 17.1 years) with symptomatic HOCM were
      enrolled in the study. All subjects underwent clinical and laboratory assessment
      before and after the procedure. Peak left ventricular outflow tract (LVOT)
      gradient was significantly reduced just after the procedure (68 vs. 20 mmHg; P <
      0.001). Peak serum creatine kinase-myocardial band and troponin I levels were 112
      (35-282) ng/ml and 11 (4-93) ng/ml. EVOH embolization to diagonal artery was
      observed in 1 patient (4%) and the complete atrioventricular block was noted in 2
      (8%) patients. During the 12-month follow-up, there was no mortality. There was a
      significant improvement in New York Heart Association functional class of the
      subjects P < 0.001). Both interventricular septum thickness and LVOT gradient
      showed a significant reduction during follow-up (P < 0.05). However, there was no
      reduction in the LVOT gradient of 3 patients (12%). CONCLUSIONS: In conclusion,
      our small-sized preliminary study results showed that septal reduction therapy
      using EVOH is an effective alternative option in reducing symptoms and LVOT
      gradient in HOCM.

PMID- 29205802
TI  - A two-center, assessor-blinded, prospective trial evaluating the efficacy of a
      novel hypertonic draining cream for cellulite reduction: A Clinical and
      instrumental (Antera 3D CS) assessment.
AB  - INTRODUCTION: Gynoid lipodystrophy, also known as cellulite, is a very common
      skin alteration representing mainly a cosmetic problem rather than a real
      disease. An effective treatment of cellulite has not been well established. The
      initial phase of cellulite is characterized by subdermal tissue edema with
      interstitial fluids retention. A new hypertonic topical product with draining
      action (HTC) containing NaCl 13%, escine, caffeine, and beta-sitosterol has been
      recently developed. A 28-day double-blind placebo-controlled study has shown that
      this cream is able to reduce thigh circumference and the thickness of adipose
      tissue. No data so far are available regarding an objective evaluation of skin
      appearance for a longer application period. STUDY AIM: To evaluate the clinical
      efficacy of 2-month HCT treatment with clinical and instrumental assessments.
      SUBJECTS AND METHODS: In a prospective, 2-center, assessor-blinded trial 20 women
      (mean age 34 years) with cellulite of Grade I-III in severity were enrolled after
      their informed consent. HTC was applied once daily for 60 days. Primary outcomes
      of the trial were the evolution of thigh circumference measurements (assessed at
      baseline, after 1 and 2 months) and the computer-analysis of skin profilometry
      (ie, skin volumes) of a prespecified target area evaluated by means of Antera 3D
      CS digitalized images (assessed at baseline and at the end of the trial).
      Secondary outcome was the orange peel severity score (from 0 to 5) before and
      after pitch test. RESULTS: All subjects concluded the study period. Thigh
      circumference was reduced by -0.88 (right)/-1.2 cm (left) and by -1.8(right)/-2.1
      (left) cm, after 30 and 60 days of treatment, respectively (P = .001, Wilcoxon
      test vs baseline). Antera 3D profilometry of the target zone showed a significant
      reduction in skin depression expressed in mm3 of -56% (from 59.7 to 26.73 mm3 )
      after HTC application. Orange peel (no pitch test) mean (SD) score was 2.3 (1) at
      baseline, 2.0 (1) and 1.8 (0.8) after 1 and 2 months (P = .0031), respectively.
      After-pitch orange peel score was significantly reduced after treatment (from 3.3
      to 2.2). CONCLUSION: Once daily application of HTC for 2 months has confirmed its
      efficacy in the improvement of objective and subjective assessments of cellulite
      parameters.(Trial Number registration: ISRCTN15111614).

PMID- 29205804
TI  - A prospective cohort study assessing the appearance of retrieved aesthetic
      orthodontic archwires.
AB  - OBJECTIVES: To investigate the appearance of three esthetic nickel titanium
      (NiTi) wires after 6 weeks of intra-oral cycling and to determine the association
      between objective and subjective measures of esthetics. SETTING AND SAMPLE
      POPULATION: A prospective cohort study was undertaken involving participants
      undergoing upper fixed orthodontic appliance treatment with ceramic brackets.
      MATERIALS AND METHODS: Fifty participants were assigned to one of three groups of
      NiTi esthetic wires (American Orthodontics Ever WhiteTM, Forestadent
      BiocosmeticTM and GAC High AestheticTM), with wires retrieved after 6 weeks in
      situ. Participants completed a bespoke questionnaire exploring perceptions of
      wire esthetics. Objective measurement of coating loss was undertaken using a
      custom arch wire jig. RESULTS: American Orthodontics Ever WhiteTM had the
      greatest mean coating loss (50.7%) followed by Forestadent BiocosmeticTM (6%),
      with GAC High Aesthetic TM undergoing minimal loss (0.07%) (P < .001). The
      majority of coating loss with the American Orthodontics Ever WhiteTM wires arose
      in the anterior region while Forestadent BiocosmeticTM wires and GAC High
      AestheticTM wires exhibited coating loss posteriorly (P < .001). These findings
      were reflected in the subjective assessment with a negative correlation found
      between coating loss and final Visual Analogue Scale scores (P < .001).
      CONCLUSIONS: Considerable esthetic variation between arch wires following 6 weeks
      of intraoral cycling was identified in this prospective cohort study. Intraoral
      cycling has a negative impact on participant perception of arch wire esthetics,
      and objective and subjective assessment of wire esthetics appears to be
      consistent.

PMID- 29205805
TI  - Herbicide resistance costs: what are we actually measuring and why?
AB  - Despite the considerable research efforts invested over the years to measure the
      fitness costs of herbicide resistance, these have rarely been used to inform a
      predictive theory about the fate of resistance once the herbicide is
      discontinued. One reason for this may be the reductive focus on relative fitness
      of two genotypes as a single measure of differential performance. Although the
      extent of variation in relative fitness between resistant and susceptible plants
      has not been assessed consistently, we know enough about plant physiology and
      ecology not to reduce it to a single fixed value. Research must therefore
      consider carefully the relevance of the experimental environment, the life stage
      and the choice of metric when measuring fitness-related traits. The reason most
      often given for measuring the cost of resistance, prediction of the impacts of
      management options on population dynamics, cannot be addressed using arbitrary
      components of fitness or a fixed value of relative fitness. To inform management
      options, the measurement of traits that capture the relevant processes and the
      main causes of their variation are required. With an emphasis on the benefit of
      field experiments measured over multiple time points and seasons, we highlight
      examples of studies that have made significant advances in this direction. (c)
      2017 Society of Chemical Industry.

PMID- 29205807
TI  - Post-operative telephone review is safe and effective: prospective study - Monash
      outpatient review by phone trial.
AB  - INTRODUCTION: Studies have shown that post-operative telephone follow-up is
      satisfactory and effective. As high quality evidence is scant, we conducted a
      randomized controlled trial to compare it against outpatient clinic review for
      emergency laparoscopic appendicectomy or cholecystectomy. METHOD: Patients who
      received emergency laparoscopic appendicectomy or cholecystectomy were eligible
      for this study. Once recruited, they were randomly allocated to either clinic
      review or telephone follow-up on discharge. Participants were reviewed at 2 weeks
      after operation and contacted again at 4 weeks after initial follow-up for
      satisfaction survey. RESULTS: One hundred and seventy-nine participants were
      recruited with one withdrawn consent and six excluded. Ninety-six underwent
      laparoscopic appendicectomy and 76 had laparoscopic cholecystectomy. Ninety-six
      attended clinic review and 76 had telephone follow-up. The two groups were
      similar in baseline variables. Non-attendance rate was higher for clinic review
      cohort (24% vs 6.6%, P = 0.002). Participants who received telephone review
      reported higher satisfaction level (9.31 vs 8.85, P = 0.002), and most patients
      prefer telephone follow-up (73.1%, P < 0.0001). No difference was detected for
      missed complications (P = 0.354). CONCLUSION: Telephone follow-up post
      laparoscopic appendicectomy or cholecystectomy is safe, satisfying and effective.

PMID- 29205806
TI  - Neuroprotection by quercetin via mitochondrial function adaptation in traumatic
      brain injury: PGC-1alpha pathway as a potential mechanism.
AB  - The aim of this study was to investigate the neuroprotective effects of quercetin
      in mouse models of traumatic brain injury (TBI) and the potential role of the PGC
      1alpha pathway in putative neuroprotection. Wild-type mice were randomly assigned
      to four groups: the sham group, the TBI group, the TBI+vehicle group and the
      TBI+quercetin group. Quercetin, a dietary flavonoid used as a food supplement,
      significantly reduced TBI-induced neuronal apoptosis and ameliorated
      mitochondrial lesions. It significantly accelerated the translocation of PGC
      1alpha protein from the cytoplasm to the nucleus. In addition, quercetin restored
      the level of cytochrome c, malondialdehyde and superoxide dismutase in
      mitochondria. Therefore, quercetin administration can potentially attenuate brain
      injury in a TBI model by increasing the activities of mitochondrial biogenesis
      via the mediation of the PGC-1alpha pathway.

PMID- 29205808
TI  - Self-Assembled Aptamer-Nanomedicine for Targeted Chemotherapy and Gene Therapy.
AB  - Chemotherapy is the mainstream treatment of anaplastic large cell lymphoma
      (ALCL). However, chemotherapy can cause severe adverse effects in patients
      because it is not ALCL-specific. In this study, a multifunctional aptamer
      nanomedicine (Apt-NMed) achieving targeted chemotherapy and gene therapy of ALCL
      is developed. Apt-NMed is formulated by self-assembly of synthetic
      oligonucleotides containing CD30-specific aptamer and anaplastic lymphoma kinase
      (ALK)-specific siRNA followed by self-loading of the chemotherapeutic drug
      doxorubicin (DOX). Apt-NMed exhibits a well-defined nanostructure (diameter 59
      mm) and stability in human serum. Under aptamer guidance, Apt-NMed specifically
      binds and internalizes targeted ALCL cells. Intracellular delivery of Apt-NMed
      triggers rapid DOX release for targeted ALCL chemotherapy and intracellular
      delivery of the ALK-specific siRNA induced ALK oncogene silencing, resulting in
      combined therapeutic effects. Animal model studies reveal that upon systemic
      administration, Apt-NMed specifically targets and selectively accumulates in ALCL
      tumor site, but does not react with off-target tumors in the same xenograft
      mouse. Importantly, Apt-NMed not only induces significantly higher inhibition in
      ALCL tumor growth, but also causes fewer or no side effects in treated mice
      compared to free DOX. Moreover, Apt-NMed treatment markedly improves the survival
      rate of treated mice, opening a new avenue for precision treatment of ALCL.

PMID- 29205809
TI  - A randomised, controlled, non-inferiority trial comparing the performance of a
      soft silicone-coated wound contact layer (Mepitel One) with a lipidocolloid wound
      contact layer (UrgoTul) in the treatment of acute wounds.
AB  - Wound contact layer (WCL) dressings are intended to protect tissue during the
      healing process. A randomised controlled trial was undertaken to compare 2 such
      dressings. Outpatients with acute wounds were randomly allocated to treatment
      with either a soft silicone-coated WCL (intervention group, n = 59) or a
      lipidocolloid-impregnated WCL (control group, n = 62). At the first dressing
      removal (day 3), 89.8% of patients in the intervention group experienced non
      painful dressing removal (defined as a pain rating <30 mm on a 100 mm visual
      analogue scale), compared with 73.6% of patients in the control group (P = .017)
      (per protocol population). At day 21, wounds were considered as healed in 66.1%
      of patients in the intervention group compared with 43.5% in the control group (P
      = .012) (intention-to-treat population). Both dressings were well tolerated and
      rated highly in terms of in-use characteristics, although the soft silicone
      coated WCL was rated significantly higher than the lipidocolloid-impregnated WCL
      in terms of its ability to remain in place (P= .016). The results indicate that
      the soft silicone-coated WCL is suitable for the management of acute wounds as it
      can minimise dressing-associated pain and support healing.

PMID- 29205810
TI  - In Situ Synthesis of Few-Layered g-C3 N4 with Vertically Aligned MoS2 Loading for
      Boosting Solar-to-Hydrogen Generation.
AB  - In artificial photocatalytic hydrogen evolution, effective incident photon
      absorption and a high-charge recombination rate are crucial factors influencing
      the overall efficiency. Herein, a traditional solid-state synthesis is used to
      obtain, for the first time, novel samples of few-layered g-C3 N4 with vertically
      aligned MoS2 loading (MoS2 /C3 N4 ). Thiourea and layered MoO3 are chosen as
      precursors, as they react under nitrogen atmosphere to in situ produce the
      products. According to the quasi-Fourier transform infrared reflectance and X-ray
      diffraction measurements, the detailed reaction process is determined to proceed
      through the confirmed formation pathway. The two precursor units MoS2 and C3 N4
      are linked by Mo?N bonds, which act as electronic receivers/conductors and
      hydrogen-generation sites. Density functional theory is also carried out, which
      determines that the interface sites act as electron-accumulation regions.
      According to the photoelectrochemical results, MoS2 /C3 N4 can achieve a current
      of 0.05 mA cm-2 , which is almost ten times higher than that of bare g-C3 N4 or
      the MoS2 /C3 N4 -R reference samples. The findings in the present work pave the
      way to not only synthesize a series of designated samples but also thoroughly
      understand the solid-state reaction.

PMID- 29205811
TI  - Prehospital analgesic choice in injured patients does not impact on rates of
      vomiting: Experience from a New South Wales primary retrieval service.
AB  - OBJECTIVE: This study aimed to explore the analgesic regimes adopted in our
      contemporary retrieval practice and the incidence of vomiting in ED after
      prehospital analgesic use. METHOD: A retrospective review was conducted on trauma
      patients retrieved by the Hunter Primary Retrieval Service in the Hunter New
      England Local Health District, New South Wales, Australia, during 2015. RESULTS:
      Of the 379 patients attended by the service in 2015, 196 of them (mean age 38.6,
      SD 19.68, years) were selected for this review. Morphine was the most commonly
      used analgesic (mean 68.37%; 95% CI 61.36-74.81%), followed by fentanyl (mean
      48.47%; 95% CI 41.29-55.70%) and ketamine (mean 34.18%; 95% CI 27.57-41.28%).
      Fourteen (7.14%, 95% CI 3.96-11.69%) patients vomited either prehospital or
      within the ED. Patients in both the emesis and the non-emesis group were
      comparable in demographics. None of the three studied analgesics were observed to
      be significantly associated with higher risk of vomiting than the others in this
      review, although a higher dose of fentanyl was given to the non-emesis group (P =
      0.04). CONCLUSIONS: The frequency of vomiting in the retrieved patients observed
      in our study was less than previously reported in the literature. Opioids still
      prevailed over ketamine as the preferred initial analgesic, with ketamine most
      commonly used as an adjunct. Multi-centre trials in this field would be
      preferable in future in view of the relatively low incidence of vomiting in
      retrieved trauma patients.

PMID- 29205812
TI  - Cu2+ -Modified Metal-Organic Framework Nanoparticles: A Peroxidase-Mimicking
      Nanoenzyme.
AB  - The synthesis and characterization of UiO-type metal-organic framework
      nanoparticles (NMOFs) composed of Zr4+ ions bridged by 2,2'-bipyridine-5,5'
      dicarboxylic acid ligands and the postmodification of the NMOFs with Cu2+ ions
      are described. The resulting Cu2+ -modified NMOFs, Cu2+ -NMOFs, exhibit
      peroxidase-like catalytic activities reflected by the catalyzed oxidation of
      Amplex-Red to the fluorescent Resorufin by H2 O2 , the catalyzed oxidation of
      dopamine to aminochrome by H2 O2 , and the catalyzed generation of
      chemiluminescence in the presence of luminol/H2 O2 . Also, the Cu2+ -NMOFs mimic
      NADH peroxidase functions and catalyze the oxidation of dihydronicotinamide
      adenine dinucleotide, NADH, to nicotinamide adenine dinucleotide, NAD+ , in the
      presence of H2 O2 . The Cu2+ -NMOFs-catalyzed generation of chemiluminescence in
      the presence of luminol/H2 O2 is used to develop a glucose sensor by monitoring
      the H2 O2 formed by the aerobic oxidation of glucose to gluconic acid in the
      presence of glucose oxidase. Furthermore, loading the Cu2+ -NMOFs with
      fluorescein and activating the catalyzed generation of chemiluminescence in the
      presence of luminol/H2 O2 yield an efficient chemiluminescence resonance energy
      transfer (CRET) process to the fluorescein reflected by the activation of the
      fluorescence of the dye (lambda = 520 nm, CRET efficiency 35%).

PMID- 29205813
TI  - High-Throughput Block Optical DNA Sequence Identification.
AB  - Optical techniques for molecular diagnostics or DNA sequencing generally rely on
      small molecule fluorescent labels, which utilize light with a wavelength of
      several hundred nanometers for detection. Developing a label-free optical DNA
      sequencing technique will require nanoscale focusing of light, a high-throughput
      and multiplexed identification method, and a data compression technique to
      rapidly identify sequences and analyze genomic heterogeneity for big datasets.
      Such a method should identify characteristic molecular vibrations using optical
      spectroscopy, especially in the "fingerprinting region" from ~400-1400 cm-1 .
      Here, surface-enhanced Raman spectroscopy is used to demonstrate label-free
      identification of DNA nucleobases with multiplexed 3D plasmonic nanofocusing.
      While nanometer-scale mode volumes prevent identification of single nucleobases
      within a DNA sequence, the block optical technique can identify A, T, G, and C
      content in DNA k-mers. The content of each nucleotide in a DNA block can be a
      unique and high-throughput method for identifying sequences, genes, and other
      biomarkers as an alternative to single-letter sequencing. Additionally, coupling
      two complementary vibrational spectroscopy techniques (infrared and Raman) can
      improve block characterization. These results pave the way for developing a
      novel, high-throughput block optical sequencing method with lossy genomic data
      compression using k-mer identification from multiplexed optical data acquisition.

PMID- 29205814
TI  - Immediate effect and safety of HIFU single treatment for male subcutaneous fat
      reduction.
AB  - BACKGROUND: The increasing search for procedures for fat reduction is related to
      dissatisfaction with body shape. High-intensity focused ultrasound (HIFU) has
      been proven effective in body sculpting when used noninvasively to reduce
      subcutaneous fat and improve body contour. AIMS: This study aimed to evaluate the
      immediate effect and safety of HIFU single treatment for male localized fat and
      body remodeling. PATIENTS/METHODS: Twenty-four male subjects (18 to 59 years old)
      with BMI <= 30 kg/cm2 and at least 2 cm of abdominal fat received a single HIFU
      treatment session. Individuals were subjected to abdominal measurements before
      and after procedure. In addition, biochemical analyses of blood samples were
      performed to assess possible inflammatory effects or oxidative stress induction
      by the treatment. RESULTS: High-intensity focused ultrasound was found to be an
      effective treatment in reducing localized adiposities in the abdominal region. A
      significant decrease (0.6%) was observed in infraumbilical circumference of
      subjects submitted to HIFU single treatment when compared with control subjects.
      The laboratory parameters did not present any appreciable changes. CONCLUSION:
      This study further strengthens the current view that HIFU is an effective and
      safe tool for localized fat reduction.

PMID- 29205815
TI  - Advocating a need for suitable breeding approaches to boost integrated pest
      management: a European perspective.
AB  - Currently, European farmers do not have access to sufficient numbers and
      diversity of crop species/varieties. This prevents them from designing cropping
      systems more resilient to abiotic and biotic stresses. Crop diversification is a
      key lever to reduce pest (pathogens, animal pests and weeds) pressures at all
      spatial levels from fields to landscapes. In this context, plant breeding should
      consist of: (1) increased efforts in the development of new or minor crop
      varieties to foster diversity in cropping systems, and (2) focus on more
      resilient varieties showing local adaptation. This new breeding paradigm, called
      here 'breeding for integrated pest management (IPM)', may boost IPM through the
      development of cultivars with tolerance or resistance to key pests, with the goal
      of reducing reliance on conventional pesticides. At the same time, this paradigm
      has legal and practical implications for future breeding programs, including
      those targeting sustainable agricultural systems. By putting these issues into
      the context, this article presents the key outcomes of a questionnaire survey and
      experts' views expressed during an EU workshop entitled 'Breeding for IPM in
      sustainable agricultural systems'. (c) 2017 Society of Chemical Industry.

PMID- 29205816
TI  - In Situ Probing of the Particle-Mediated Mechanism of WO3 -Networked Structures
      Grown inside Confined Mesoporous Channels.
AB  - Nanocasting, using ordered mesoporous silica or carbon as a hard template, has
      enormous potential for preparing novel mesoporous materials with new structures
      and compositions. Although a variety of mesoporous materials have been
      synthesized in recent years, the growth mechanism of nanostructures in a confined
      space, such as mesoporous channels, is not well understood, which hampers the
      controlled synthesis and further application of mesoporous materials. Here, the
      nucleation and growth of WO3 -networked mesostructures within an ordered
      mesoporous matrix, using an in situ transmission electron microscopy heating
      technique and in situ synchrotron small-angle X-ray scattering spectroscopy, are
      probed. It is found that the formation of WO3 mesostructures involves a particle
      mediated transformation and coalescence mechanism. The liquid-like particle
      mediated aggregation and mesoscale transformation process can occur in ~10 nm
      confined mesoporous channels, which is completely unexpected. The detailed
      mechanistic study will be of great help for experimental design and to exploit a
      variety of mesoporous materials for diverse applications, such as catalysis,
      absorption, separation, energy storage, biomedicine, and nanooptics.

PMID- 29205817
TI  - Electron Holographic Study of Semiconductor Light-Emitting Diodes.
AB  - Semiconductor light-emitting diodes (LEDs), especially GaN-based
      heterostructures, are widely used in light illumination. The lack of inversion
      symmetry of wurtzite crystal structures and the lattice mismatch at
      heterointerfaces cause large polarization fields with contributions from both
      spontaneous polarization and piezoelectric polarization, which in turn results in
      obvious quantum confined stark effect. It is possible to alleviate this effect if
      the local electrostatic fields and band alignment induced charge redistribution
      can be quantitatively determined across the heterostructures. In this Concept,
      the applications of electron holography to investigate semiconductor LEDs are
      summarized. Following the off-axis electron holography scheme, the GaN-based LED
      heterostructures including InGaN/GaN-based quantum wells, other GaN-based quantum
      wells, and other forms of GaN-based LED materials are discussed, focusing on the
      local potential drops, polarization fields, and charge distributions. Moreover,
      GaAs-based LED heterostructures are briefly discussed. The in-line electron
      holography scheme emphasizes the capability of large area strain mapping across
      LED heterostructures with high spatial resolution and accuracy, which is combined
      with quantitative electrostatic measurements and other advanced transmission
      electron microscopy characterizations to provide an overall nanometer scale
      perspective of LED devices for further improvement in their electric and optical
      properties.

PMID- 29205818
TI  - Ultrathin Nanosheet Assembled Sn0.91 Co0.19 S2 Nanocages with Exposed (100)
      Facets for High-Performance Lithium-Ion Batteries.
AB  - Ultrathin 2D inorganic nanomaterials are good candidates for lithium-ion
      batteries, as well as the micro/nanocage structures with unique and tunable
      morphologies. Meanwhile, as a cost-effective method, chemical doping plays a
      vital role in manipulating physical and chemical properties of metal oxides and
      sulfides. Thus, the design of ultrathin, hollow, and chemical doped metal
      sulfides shows great promise for the application of Li-ion batteries by
      shortening the diffusion pathway of Li ions as well as minimizing the electrode
      volume change. Herein, ultrathin nanosheet assembled Sn0.91 Co0.19 S2 nanocages
      with exposed (100) facets are first synthesized. The as-prepared electrode
      delivers an excellent discharge capacity of 809 mA h g-1 at a current density of
      100 mA g-1 with a 91% retention after 60 discharge-charge cycles. The
      electrochemical performance reveals that the Li-ion batteries prepared by Sn0.91
      Co0.19 S2 nanocages have high capacity and great cycling stability.

PMID- 29205819
TI  - Natural variation of hormone levels in Arabidopsis roots and correlations with
      complex root architecture.
AB  - Studies on natural variation are an important tool to unravel the genetic basis
      of quantitative traits in plants. Despite the significant roles of phytohormones
      in plant development, including root architecture, hardly any studies have been
      done to investigate natural variation in endogenous hormone levels in plants.
      Therefore, in the present study a range of hormones were quantified in root
      extracts of thirteen Arabidopsis thaliana accessions using a ultra performance
      liquid chromatography triple quadrupole mass spectrometer. Root system
      architecture of the set of accessions was quantified, using a new parameter
      (mature root unit) for complex root systems, and correlated with the phytohormone
      data. Significant variations in phytohormone levels among the accessions were
      detected, but were remarkably small, namely less than three-fold difference
      between extremes. For cytokinins, relatively larger variations were found for
      ribosides and glucosides, as compared to the free bases. For root phenotyping,
      length-related traits-lateral root length and total root length-showed larger
      variations than lateral root number-related ones. For root architecture,
      antagonistic interactions between hormones, for example, indole-3-acetic acid to
      trans-zeatin were detected in correlation analysis. These findings provide
      conclusive evidence for the presence of natural variation in phytohormone levels
      in Arabidopsis roots, suggesting that quantitative genetic analyses are feasible.

PMID- 29205821
TI  - Re: Impact of pre-operative health-related quality of life on outcomes after
      heart surgery.

PMID- 29205822
TI  - Routine reporting of mammographic density from screening mammograms.

PMID- 29205823
TI  - Re: Laboratory Risk Indicator for Necrotizing Fasciitis score for early diagnosis
      of necrotizing fasciitis in Darwin.

PMID- 29205824
TI  - Re: How to do it: use of the Alexis wound protector as a laparostomy device.

PMID- 29205825
TI  - Let's make the most of the underutilized capacity of the private hospital system
      for educating our future surgical workforce.

PMID- 29205826
TI  - The World Health Organization Surgical Safety Checklist.

PMID- 29205827
TI  - Response to Re: Impact of pre-operative health-related quality of life on
      outcomes after heart surgery.

PMID- 29205829
TI  - Acknowledging pancreaticoduodenectomy as a multi-visceral resection.

PMID- 29205830
TI  - Medicine in small doses.

PMID- 29205831
TI  - Response to Re: Laboratory Risk Indicator for Necrotizing Fasciitis score for
      early diagnosis of necrotizing fasciitis in Darwin.

PMID- 29205832
TI  - Antipsychotic drug-induced hypoglycemia and hypothermia.
AB  - This case report comprises three cases of antipsychotic drug-induced hypoglycemia
      and hypothermia. The mechanisms behind these side-effects are not known, but in
      hypoglycemia we describe signs of inappropriate insulin secretion. We assume that
      antipsychotic drug-induced hypoglycemia and hypothermia are underdiagnosed.
      Antipsychotic drugs are, however, widely used and these rare adverse-effects may
      occur in the clinical practice. It is of utmost importance to measure blood
      glucose and body temperature of patients taking these drugs who have unspecific
      symptoms.

PMID- 29205834
TI  - Validation of Alcohol Flushing Questionnaires in Determining Inactive Aldehyde
      Dehydrogenase-2 and Its Clinical Implication in Alcohol-Related Diseases.
AB  - BACKGROUND: Our aim was to validate alcohol flushing questionnaires in detecting
      inactive ALDH2 (ALDH2*1/*2 or ALDH2*2/*2). METHODS: Two study sets were
      established; in study set 1, 210 healthy male subjects (age 22 to 59 years) were
      enrolled; in study set 2, 756 subjects were enrolled who received
      esophagogastroduodenoscopy to evaluate their dyspeptic symptoms or as part of a
      gastric cancer screening program. Subjects in study sets 1 and 2 completed the
      modified alcohol flushing questionnaires of Yokoyama and colleagues (, ).
      Polymerase chain reaction-restriction fragment length polymorphism method was
      used to determine ALDH2 genotype. RESULTS: In study set 1, 29.0% (61 of 210) had
      inactive ALDH2. The sensitivity and specificity of the modified alcohol flushing
      questionnaire for detecting inactive ALDH2 were 95.1 and 76.5%, respectively.
      Drinking problems negatively correlated with positive alcohol flushing response
      and inactive ALDH2 (all p-values < 0.05). In study set 2, the sensitivity and
      specificity of the alcohol flushing questionnaire for detecting inactive ALDH2
      were 78.9 and 82.1%, respectively. Interestingly, drinking >=7 units/wk in men or
      >=3.5 units/wk in women significantly increased the risk of benign gastric ulcer
      (BGU) among positive alcohol flushers (odds ratio, 8.97; 95% confidence interval,
      1.38 to 58.30), but not among negative alcohol flushers. CONCLUSIONS: Simple
      flushing questionnaires may be administered to the Korean population as a
      screening tool in detecting individuals who carry inactive ALDH2. Alcohol
      flushing response negatively correlates with drinking problems and can modify the
      risk for BGU by alcohol intake.

PMID- 29205833
TI  - Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage
      cells to metabolic stresses.
AB  - AIMS: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to
      be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes
      is considered a contributing factor to white matter dysfunction. However, little
      is known about the energy processing characteristics of oligodendrocyte lineage
      cells under basal and metabolic stress conditions. The aim of this study was to
      identify the energy requirements and cellular responses of oligodendrocytes at
      different developmental stages. METHODS: We compared the metabolic stress
      responses between myelinating oligodendrocytes (OLs) and oligodendrocyte
      precursor cells (OPCs). Differential regulation of cellular response was also
      investigated. RESULTS: We found that, following cerebral ischemia,
      monocarboxylate transporter 1 (MCT1) expression was upregulated in the peri
      infarct striatum but not in the cortex of the brain. In vitro ischemia models
      were used to induce oligodendrocyte stress as well. An increase in MCT1
      expression was detected in OPCs after a mild oxygen-glucose deprivation. Double
      labeled immunohistochemical analysis revealed that OPCs and OLs responded
      differently to metabolic stresses and that the susceptibility to metabolic
      stresses of OPCs and OLs was associated with their distinct expression profiles
      of MCT1. CONCLUSION: Taken together, this study shows that MCT1 plays a role in
      the responses of OPCs and OLs to metabolic and ischemic stresses and suggests
      that redistribution of energy substrates is a determinant in white matter injury.

PMID- 29205835
TI  - Colonoscopy conversion after flexible sigmoidoscopy screening: results from the
      UK Bowel Scope Screening Programme.
AB  - AIM: In the UK Bowel Scope Screening Programme (BSSP), patients progress to
      colonoscopy based on high-risk features on flexible sigmoidoscopy (FS). We aim to
      assess the practice of colonoscopy conversion and predictors of detection of
      additional adenomas on colonoscopy. METHOD: The Bowel Cancer Screening database
      was interrogated and collated with endoscopic and histological findings from
      patients undergoing colonoscopy following FS between August 2013 and August 2016.
      Multivariate analysis was performed to identify predictors of new adenomas.
      RESULTS: FS was performed on 11 711 patients, with an adenoma detection rate
      (ADR) of 8.5% and conversion to colonoscopy in 421 (3.6%). The additional ADR at
      colonoscopy was 35.2%, with one additional malignant diagnosis (0.26%). The
      adenoma miss rate was 3.6%. On multivariate analysis, a polyp >= 10 mm was the
      only high-risk indication associated with additional ADR at colonoscopy (OR 3.68,
      95% CI 1.51-3.65, P < 0.001), in addition to male gender (OR 2.36, 95% CI 1.46
      3.83, P < 0.001). Predictors of detection of a new adenoma >= 10 mm included:
      villous adenoma (P = 0.002), polyp >= 10 mm (P = 0.007) and male gender (P =
      0.039). The presence of any conversion criterion was associated with the
      detection of any proximal adenoma (P < 0.001) and adenoma >= 10 mm (P = 0.031).
      CONCLUSION: Male gender, polyps >= 10 mm and villous-preponderant histology at FS
      were predictors of adenomas < 10 mm and >= 10 mm at colonoscopy. Further data are
      required to assess the role for gender-based stratification of conversion
      criteria.

PMID- 29205836
TI  - Recent Progress of Textile-Based Wearable Electronics: A Comprehensive Review of
      Materials, Devices, and Applications.
AB  - Wearable electronics are emerging as a platform for next-generation, human
      friendly, electronic devices. A new class of devices with various functionality
      and amenability for the human body is essential. These new conceptual devices are
      likely to be a set of various functional devices such as displays, sensors,
      batteries, etc., which have quite different working conditions, on or in the
      human body. In these aspects, electronic textiles seem to be a highly suitable
      possibility, due to the unique characteristics of textiles such as being light
      weight and flexible and their inherent warmth and the property to conform.
      Therefore, e-textiles have evolved into fiber-based electronic apparel or body
      attachable types in order to foster significant industrialization of the key
      components with adaptable formats. Although the advances are noteworthy, their
      electrical performance and device features are still unsatisfactory for consumer
      level e-textile systems. To solve these issues, innovative structural and
      material designs, and novel processing technologies have been introduced into e
      textile systems. Recently reported and significantly developed functional
      materials and devices are summarized, including their enhanced optoelectrical and
      mechanical properties. Furthermore, the remaining challenges are discussed, and
      effective strategies to facilitate the full realization of e-textile systems are
      suggested.

PMID- 29205837
TI  - COMP report: CPQR technical quality control guideline for medical linear
      accelerators and multileaf collimators.
AB  - The Canadian Organization of Medical Physicists (COMP), in close partnership with
      the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series
      of Technical Quality Control (TQC) guidelines for radiation treatment equipment.
      These guidelines outline the performance objectives that equipment should meet in
      order to ensure an acceptable level of radiation treatment quality. The TQC
      guidelines have been rigorously reviewed and field tested in a variety of
      Canadian radiation treatment facilities. The development process enables rapid
      review and update to keep the guidelines current with changes in technology (the
      most updated version of this guideline can be found on the CPQR website). This
      particular TQC details recommended quality control testing for medical linear
      accelerators and multileaf collimators.

PMID- 29205838
TI  - Enhanced Performance of MoS2 Photodetectors by Inserting an ALD-Processed TiO2
      Interlayer.
AB  - 2D molybdenum disulfide (MoS2 ) possesses excellent optoelectronic properties
      that make it a promising candidate for use in high-performance photodetectors.
      Yet, to meet the growing demand for practical and reliable MoS2 photodetectors,
      the critical issue of defect introduction to the interface between the exfoliated
      MoS2 and the electrode metal during fabrication must be addressed, because
      defects deteriorate the device performance. To achieve this objective, the use of
      an atomic layer-deposited TiO2 interlayer (between exfoliated MoS2 and electrode)
      is reported in this work, for the first time, to enhance the performance of MoS2
      photodetectors. The TiO2 interlayer is inserted through 20 atomic layer
      deposition cycles before depositing the electrode metal on MoS2 /SiO2 substrate,
      leading to significantly enhanced photoresponsivity and response speed. These
      results pave the way for practical applications and provide a novel direction for
      optimizing the interlayer material.

PMID- 29205839
TI  - Canine nodal marginal zone lymphoma: Descriptive insight into the biological
      behaviour.
AB  - Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma.
      Such lymphomas are typified by low mitotic rate and slow clinical progression.
      While the clinical behaviour of canine splenic MZL has been described,
      characterized by an indolent course and a good prognosis following splenectomy,
      there are no studies specifically describing nMZL. The aim of this study was to
      describe the clinical features of and outcome for canine nMZL. Dogs with
      histologically confirmed nMZL undergoing a complete staging work-up (including
      blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone
      marrow, imaging, histology and immunohistochemistry on a surgically removed
      peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy
      or chemo-immunotherapy. Endpoints were response rate (RR), time to progression
      (TTP) and lymphoma-specific survival (LSS). A total of 35 cases were enrolled. At
      diagnosis, all dogs showed generalized lymphadenopathy. One-third was
      systemically unwell. All dogs had stage V disease; one-third also had extranodal
      involvement. The LN population was mainly composed of medium-sized CD21+ cells
      with scant resident normal lymphocytes. Histology revealed diffuse LN
      involvement, referring to "late-stage" MZL. Median TTP and LSS were 149 and 259
      days, respectively. Increased LDH activity and substage b were significantly
      associated with a shorter LSS. Dogs with nMZL may show generalized
      lymphadenopathy and an advanced disease stage. Overall, the outcome is poor,
      despite the "indolent" designation. The best treatment option still needs to be
      defined.

PMID- 29205840
TI  - Multiple-Level Porous Polymer Monoliths with Interconnected Cellular Topology
      Prepared by Combining Hard Sphere and Emulsion Templating for Use in Bone Tissue
      Engineering.
AB  - A combination of hard sphere and high internal phase emulsion templating gives a
      platform for synthesizing hierarchically porous polymers with a unique topology
      exhibiting interconnected spherical features on multiple levels. Polymeric
      spheres are fused by thermal sintering to create a 3D monolithic structure while
      an emulsion with a high proportion of internal phase and monomers in the
      continuous phase is added to the voids of the previously constructed monolith.
      Following polymerization of the emulsion and dissolution of the templating
      structure, a down-replicating topology is created with a primary level of pores
      as a result of fused spheres of the 3D monolithic structure, a secondary level of
      pores resulting from the emulsion's internal phase, and a tertiary level of
      interconnecting channels. Thiol-ene chemistry with divinyladipate and
      pentaerythritol tetrakis(3-mercaptopropionate) is used to demonstrate the
      preparation of a crosslinked polyester with overall porosity close to 90%. Due to
      multilevel porosity, such materials are interesting for applications in bone
      tissue engineering, possibly simulating the native sponge like bone structure.
      Their potential to promote ossteointegration is tested using human bone derived
      osteoblasts. Material-cell interactions are evaluated and they reveal growth and
      proliferation of osteoblasts both on surface and in the bulk of the scaffold.

PMID- 29205842
TI  - To review or not to review ...?

PMID- 29205841
TI  - Catheter-associated urinary tract infection in patients treated for acute urinary
      retention is common.

PMID- 29205843
TI  - Ageing and the economic life cycle: The National Transfer Accounts approach.
AB  - OBJECTIVE: To illustrate the use of National Transfer Accounts (NTA) for
      understanding ageing and the economic life cycle in Australia. METHODS: The NTA
      methodology is applied utilising a range of unit record, demographic and
      administrative data sets from 1981 to 2010. RESULTS: During early and later life,
      total consumption (public and private) is greater than labour income. On a time
      series and cohort basis, we show that each successive generation has improved
      their level of well-being (as measured by consumption) relative to the previous
      years or previous cohorts from 1981 to 1982 onwards. We also show a substantial
      increase in labour income earned by mature age workers over this period.
      International comparisons show Australia to have consumption and labour income
      age profiles very similar to those of Canada but dissimilar to many other
      countries, driven by differences in demographic and policy settings. CONCLUSION:
      The NTA approach provides a powerful framework to track differences in the
      economic life cycle across age groups, across time, across cohorts and across
      countries.

PMID- 29205844
TI  - 'It keeps dropping out!': The need to address the ongoing digital divide to
      achieve improved health and well-being benefits for older rural Australians.

PMID- 29205845
TI  - Private and public consumption across generations in Australia.
AB  - OBJECTIVE: To investigate intergenerational equity in consumption using the
      Australian National Transfer Accounts (NTA). METHODS: Australian NTA estimates of
      consumption were used to investigate disparities in consumption between people of
      different ages and generations in Australia between 1981-1982 and 2009-2010.
      RESULTS: There is a clear patterning of consumption by age, with the distribution
      by age of consumption funded by the private sector being very different to that
      of consumption funded by the public sector. Australians have achieved notable
      equality in total consumption among people between the ages of 20 and 75 years.
      Substantial disparities exist, however, between different generations, with
      earlier generations experiencing lower levels of total consumption in real terms
      at particular ages than later generations. CONCLUSION: An accurate picture of
      intergenerational equity in consumption requires consideration of both cohorts
      and cross sections, as well as consumption funded by both the public and the
      private sectors.

PMID- 29205846
TI  - Use and clinical efficacy of standard and health information technology fall risk
      assessment tools.
AB  - OBJECTIVE: To evaluate the health information technology (HIT) compared to Fall
      Risk for Older Persons (FROP) tool in fall risk screening. METHODS: A HIT tool
      trial was conducted on the geriatric evaluation and management (GEM, n = 111) and
      acute medical units (AMU, n = 424). RESULTS: Health information technology and
      FROP scores were higher on GEM versus AMU, with no differences between people who
      fell and people who did not fall. Both score completion rates were similar, and
      their values correlated marginally (Spearman's correlation coefficient 0.33, P <
      0.01). HIT and FROP scores demonstrated similar sensitivity (80 vs 82%) and
      specificity (32 vs 36%) for detecting hospital falls. Hospital fall rates trended
      towards reduction on AMU (4.20 vs 6.96, P = 0.15) and increase on GEM (10.98 vs
      6.52, P = 0.54) with HIT tool implementation. CONCLUSIONS: Health information
      technology tool acceptability and scoring were comparable to FROP screening, with
      mixed effects on fall rate with HIT tool implementation. Clinician partnership
      remains key to effective tool development.

PMID- 29205847
TI  - Population ageing and the labour force: 2000-2015 and 2015-2030.
AB  - OBJECTIVE: To examine the role of variations in mature age labour force
      participation on labour force outcomes over Australia's recent past (2000-2015)
      and immediate future (to 2030). METHODS: To estimate the impact of rises in
      mature age participation on observed labour supply, we utilise demographic
      decomposition techniques. To examine future labour supply (to 2030), we simulate
      scenarios utilising a cohort-component projection model. RESULTS: Observed
      increases in mature age participation between 2000 and 2015 added approximately
      786 000 mature age workers to the Australian labour force. Over the proceeding 15
      years (2015-2030), conservative changes to prevailing mature age participation
      would add 304 000 additional workers. The speed of ageing is projected to
      increase and labour supply growth decrease in the next 15 years relative to that
      observed from 2000 to 2015. CONCLUSION: To benefit from increased mature age
      labour force participation, the barriers to mature age participation must be
      addressed.

PMID- 29205849
TI  - Editorial: The microbiome as a source of new enterprises and job creation.

PMID- 29205848
TI  - The efficacy, biodistribution and safety of an inhibin DNA vaccine delivered by
      attenuated Salmonella choleraesuis.
AB  - DNA vaccines, the third-generation vaccines, were extensively studied. The
      attenuated Salmonella choleraesuis (S. choleraesuis) was widely focused as a
      carrier to deliver DNA vaccines in the chromosome-plasmid balanced-lethal system.
      The efficacy of inhibin DNA vaccine delivered by attenuated S. choleraesuis was
      proved in mice and cows in our previous studies. In this study, the efficacy of
      inhibin DNA vaccine was confirmed in rhesus monkeys. To further study the
      biodistribution and safety, the mice were immunized under laboratory conditions.
      The results of the rhesus monkeys showed the plasma IgA and IgG titres against
      inhibin were elevated, and the oestradiol (E2 ) and progesterone (P4 ) levels
      were increased with immunizing inhibin DNA vaccine. The biodistribution and
      safety assessment displayed the body weight, pathological change and haematology
      indexes where there is no significant difference between vaccinated mice and
      control. And the genomics analysis showed there was no integration of the inhibin
      gene into the mouse genome 2 months after immunization. This study indicated the
      inhibin DNA vaccine delivered by attenuated S. choleraesuis was safe. And this
      vaccine was a potential means to improve their reproductive traits in primates
      and other animals.

PMID- 29205850
TI  - OTS1-dependent deSUMOylation increases tolerance to high copper levels in
      Arabidopsis.
AB  - The conjugation of SUMO (small ubiquitin-like modifier) to protein substrates is
      a reversible process (SUMOylation/deSUMOylation) that regulates plant development
      and stress responses. The essential metal copper (Cu) is required for normal
      plant growth, but excess amounts are toxic. The SUMO E3 ligase, SIZ1, and SIZ1
      mediated SUMOylation function in plant tolerance to excess Cu. It is unknown
      whether deSUMOylation also contributes to Cu tolerance in plants. Here, we report
      that OTS1, a protease that cleaves SUMO from its substrate proteins, participates
      in Cu tolerance in Arabidopsis thaliana (Arabidopsis). OTS1 loss-of-function
      mutants (ots1-2 and ots1-3) displayed increased sensitivity to excess Cu. Redox
      homeostasis and the balance between SUMOylation and deSUMOylation were disrupted
      in the ots1-3 mutant under excess Cu conditions. The ots1-3 mutant accumulated
      higher levels of Cu in both shoots and roots compared to wild type. Specific Cu
      related metal transporter genes were upregulated due to the loss-of-function of
      OTS1, which might explain the high Cu levels in ots1-3. These results suggest
      that the SUMOylation/deSUMOylation machinery is activated in response to excess
      Cu, and modulates Cu homeostasis and tolerance by regulating both Cu uptake and
      detoxification. Together, our findings provide insight into the biological
      function and regulatory role of SUMOylation/deSUMOylation in plant tolerance to
      Cu.

PMID- 29205851
TI  - Regulated Cell Death of Lymphoma Cells after Graded Mitochondrial Damage is
      Differentially Affected by Drugs Targeting Cell Stress Responses.
AB  - Collapse of the mitochondrial membrane potential (MMP) is often considered the
      initiation of regulated cell death (RCD). Carbonyl cyanide 3
      chlorophenylhydrazone (CCCP) is an uncoupler of the electron transport chain
      (ETC) that facilitates the translocation of protons into the mitochondrial matrix
      leading to the collapse of the MMP. Several cell stress responses such as
      mitophagy, mitochondrial biogenesis and the ubiquitin proteasome system may
      differentially contribute to restrain the initiation of RCD depending on the
      extent of mitochondrial damage. We induced graded mitochondrial damage after
      collapse of MMP with the mitochondrial uncoupler CCCP in Burkitt's lymphoma
      cells, and we evaluated the effect of several drugs targeting cell stress
      responses over RCD at 72 hr, using a multiparametric flow cytometry approach.
      CCCP caused collapse of MMP after 30 min., massive mitochondrial fission,
      oxidative stress and increased mitophagy within the 5-15 MUM low-dose range (LDR)
      of CCCP. Within the 20-50 MUM high-dose range (HDR), CCCP caused lysosomal
      destabilization and rupture, thus precluding mitophagy and autophagy. Cell death
      after 72 hr was below 20%, with increased mitochondrial mass (MM). The inhibitors
      of mitophagy 3-(2,4-dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)
      quinazolinone (Mdivi-1) and vincristine (VCR) increased cell death from CCCP
      within the LDR, while valproic acid (an inducer of mitochondrial biogenesis) also
      increased MM and cell death within the LDR. The proteasome inhibitor, MG132,
      increased cell death only in the HDR. Doxycycline, an antibiotic that disrupts
      mitochondrial biogenesis, had no effect on cell survival, while iodoacetamide, an
      inhibitor of glycolysis, increased cell death at the HDR. We conclude that
      mitophagy influenced RCD of lymphoma cells after MMP collapse by CCCP only within
      the LDR, while proteasome activity and glycolysis contributed to survival in the
      HDR under extensive mitochondria and lysosome damage.

PMID- 29205852
TI  - Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and
      Cancer Treatment In Vivo.
AB  - Mitochondria-mediated apoptosis (MMA) is a preferential option for cancer therapy
      due to the presence of cell-suicide factors in mitochondria, however, low
      permeability of mitochondria is a bottleneck for targeting drug delivery. In this
      paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is
      found to be a novel mitochondria targeting ligand, which can improve
      mitochondrial permeability and enhance the drug uptake of mitochondria. GA
      functionalized graphene oxide (GO) is prepared and used as an effective carrier
      for targeted delivery of doxorubicin into mitochondria. The detailed in vitro and
      in vivo mechanism study shows that GA-functionalized GO causes a decrease in
      mitochondrial membrane potential and activates the MMA pathway. The GA
      functionalized drug delivery system demonstrates highly improved apoptosis
      induction ability and anticancer efficacy compared to the non-GA-functionalized
      nanocarrier delivery system. The GA-functionalized nanocarrier also shows low
      toxicity, suggesting that it can be a useful tool for drug delivery.

PMID- 29205853
TI  - Comparative Study of In Situ Loaded Antibody and PEG-Fab NIPAAM Gels.
AB  - Hydrogels can potentially prolong the release of a therapeutic protein,
      especially to treat blinding conditions. One challenge is to ensure that the
      protein and hydrogel are intimately mixed by better protein entanglement within
      the hydrogel. N-isopropylacrylamide (NIPAAM) gels are optimized with
      poly(ethylene glycol) diacrylate (PEDGA) crosslinker in the presence of either
      bevacizumab or PEG conjugated ranibizumab (PEG10 -Fabrani ). The release profiles
      of the hydrogels are evaluated using an outflow model of the eye, which is
      previously validated for human clearance of proteins. Release kinetics of in situ
      loaded bevacizumab-NIPAAM gels displays a prolonged bimodal release profile in
      phosphate buffered saline compared to bevacizumab loaded into a preformed NIPAAM
      gel. Bevacizumab release in simulated vitreous from in situ loaded gels is
      similar to bevacizumab control indicating that diffusion through the vitreous
      rather than from the gel is rate limiting. Ranibizumab is site-specifically
      PEGylated by disulfide rebridging conjugation. Prolonged and continuous release
      is observed with the in situ loaded PEG10 -Fabrani -NIPAAM gels compared to PEG10
      -Fabrani injection (control). Compared to an unmodified protein, there is better
      mixing due to PEG entanglement and compatibility of PEG10 -Fabrani within the
      NIPAAM-PEDGA hydrogel. These encouraging results suggest that the extended
      release of PEGylated proteins in the vitreous can be achieved using injectable
      hydrogels.

PMID- 29205854
TI  - Quality evaluation of Eucommiae Cortex processed by different methods and
      "sweating" conditions based on simultaneous determination of multiple bioactive
      constituents combined with gray relational analysis.
AB  - Eucommiae Cortex is a classical traditional Chinese medicine, which needs to be
      processed by "sweating" methods. To select the suitable processing method and
      "sweating" processing condition for Eucommiae Cortex, in this study, the quality
      of Eucommiae Cortex was evaluated based on simultaneous determination of multiple
      bioactive constituents combined with gray relational analysis. The contents of
      lignans, iridoids, penylpropanoids, flavonoids, and phenols in samples were
      simultaneously determined using ultra-fast performance liquid chromatography
      coupled with triple quadrupole-linear ion trap tandem mass spectrometry. The
      chromatographic separation was performed on a Synergi? Hydro-RP 100 A column (100
      mm * 2.0 mm, 2.5 MUm) at 30 degrees C with a gradient elution of acetonitrile
      with 0.1% formic acid/0.1% aqueous formic acid as the mobile phase. Furthermore,
      gray relational analysis was performed to evaluate and sort the samples according
      to the contents of 14 constituents by calculating the relative correlation degree
      of each sample. The results demonstrated that the quality of Eucommiae Cortex
      "sweating" at source area was better and the better "sweating" condition was to
      scrape off the cork layer before "sweating" with straw covering and sun drying.
      The developed method could provide the foundation and support for "sweating"
      processing method of Eucommiae Cortex in normalization and standardization.

PMID- 29205856
TI  - Use and effectiveness of a fixed-ratio combination of insulin
      degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes:
      Results from a European, multicentre, retrospective chart review study.
AB  - AIMS: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio
      combination of the basal insulin degludec, and the glucagon-like peptide-1
      receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European,
      multicentre, retrospective chart review comprised adults (n = 611) with type 2
      diabetes, who started IDegLira >=6 months before data collection. Clinical
      characteristics were assessed at baseline (defined as the most recent recording
      during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12
      months (+/- 45 days for each time point) after commencing IDegLira, where data
      were available. RESULTS: Baseline regimens included non-injectable medications
      (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP
      1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all +/- oral
      antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c)
      reductions were observed in patients overall and in all subgroups (-10 mmol/mol [
      0.9%] overall; P < .0001), and a significant reduction in mean body weight (-0.7
      kg; P < .05) was observed in patients overall and in patients receiving MDI (-2.4
      kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at
      initiation, and at 6 and 12 months follow-up, respectively. In total, only 67
      patients reached the maximum 50 dose steps, with most coming from the free
      combination therapy (n = 31) or MDI (n = 15) baseline regimen groups.
      Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6
      month period after vs before IDegLira initiation. Overall, a total of 12 patients
      experienced 15 events in the 6 months after IDegLira initiation. CONCLUSION: In
      real-world practice, after 6 months and at a moderate dose, IDegLira resulted in
      substantial reductions in HbA1c and body weight, with a reduced risk of
      hypoglycaemia.

PMID- 29205857
TI  - Bionomics of livestock-associated Culicoides (biting midge) bluetongue virus
      vectors under laboratory conditions.
AB  - This research contributes to knowledge of the basic bionomic parameters of vector
      and non-vector Culicoides species. Field-collected gravid C. imicola and
      Obsoletus complex showed the longest lifespans in laboratory conditions.
      Culicoides paolae and C. circumscriptus seemed to be the most suitable species
      for laboratory rearing in view of their high oviposition rates, short lifecycles,
      long adult lifespans and female-biased sex ratios.

PMID- 29205855
TI  - Multilevel factors are associated with immunosuppressant nonadherence in heart
      transplant recipients: The international BRIGHT study.
AB  - Factors at the level of family/healthcare worker, organization, and system are
      neglected in medication nonadherence research in heart transplantation (HTx). The
      4-continent, 11-country cross-sectional Building Research Initiative Group:
      Chronic Illness Management and Adherence in Transplantation (BRIGHT) study used
      multistaged sampling to examine 36 HTx centers, including 36 HTx directors, 100
      clinicians, and 1397 patients. Nonadherence to immunosuppressants-defined as any
      deviation in taking or timing adherence and/or dose reduction-was assessed using
      the Basel Assessment of Adherence to Immunosuppressive Medications Scale(c)
      (BAASIS(c) ) interview. Guided by the Integrative Model of Behavioral Prediction
      and Bronfenbrenner's ecological model, we analyzed factors at these multiple
      levels using sequential logistic regression analysis (6 blocks). The nonadherence
      prevalence was 34.1%. Six multilevel factors were associated independently
      (either positively or negatively) with nonadherence: patient level: barriers to
      taking immunosuppressants (odds ratio [OR]: 11.48); smoking (OR: 2.19);
      family/healthcare provider level: frequency of having someone to help patients
      read health-related materials (OR: 0.85); organization level: clinicians
      reporting nonadherent patients were targeted with adherence interventions (OR:
      0.66); pickup of medications at physician's office (OR: 2.31); and policy level:
      monthly out-of-pocket costs for medication (OR: 1.16). Factors associated with
      nonadherence are evident at multiple levels. Improving medication nonadherence
      requires addressing not only the patient, but also family/healthcare provider,
      organization, and policy levels.

PMID- 29205858
TI  - Foot-and-mouth disease virus transmission dynamics and persistence in a herd of
      vaccinated dairy cattle in India.
AB  - Foot-and-mouth disease (FMD) is an important transboundary disease with
      substantial economic impacts. Although between-herd transmission of the disease
      has been well studied, studies focusing on within-herd transmission using farm
      level outbreak data are rare. The aim of this study was to estimate parameters
      associated with within-herd transmission, host physiological factors and FMD
      virus (FMDV) persistence using data collected from an outbreak that occurred at a
      large, organized dairy farm in India. Of 1,836 regularly vaccinated, adult dairy
      cattle, 222 had clinical signs of FMD over a 39-day period. Assuming homogenous
      mixing, a frequency-dependent compartmental model of disease transmission was
      built. The transmission coefficient and basic reproductive number were estimated
      to be between 16.2-18.4 and 67-88, respectively. Non-pregnant animals were more
      likely to manifest clinical signs of FMD as compared to pregnant cattle. Based on
      oropharyngeal fluid (probang) sampling and FMDV-specific RT-PCR, four of 36
      longitudinally sampled animals (14%) were persistently infected carriers 10.5
      months post-outbreak. There was no statistical difference between subclinical and
      clinically infected animals in the duration of the carrier state. However,
      prevalence of NSP-ELISA antibodies differed significantly between subclinical and
      clinically infected animals 12 months after the outbreak with 83% seroprevalence
      amongst clinically infected cattle compared to 69% of subclinical animals. This
      study further elucidates within-herd FMD transmission dynamics during the acute
      phase and characterizes duration of FMDV persistence and seroprevalence of FMD
      under natural conditions in an endemic setting.

PMID- 29205859
TI  - A Monodispersed Spherical Zr-Based Metal-Organic Framework Catalyst, Pt/Au@Pd@UIO
      66, Comprising an Au@Pd Core-Shell Encapsulated in a UIO-66 Center and Its Highly
      Selective CO2 Hydrogenation to Produce CO.
AB  - A Zr-based metal-organic framework (MOF) catalyst, Pt/Au@Pd@UIO-66, is assembled,
      where UIO-66 is Zr6 O4 (OH)4 (BDC)6 (BDC = 1,4-benzenedicarboxylate). The gold
      nanoparticles (NPs) act as the core for the epitaxial growth of Pd shells, and
      the core-shell monodispersed nanosphere Au@Pd is encapsulated into UIO-66 to
      control its morphology and impart nanoparticle functionality. The microporous
      nature of UIO-66 assists the adsorption of Pt NPs, which in turn enhances the
      interaction between NPs and UIO-66, favoring the formation of isolated and well
      dispersed Pt NP active sites. This MOF exhibits high catalytic activity and CO
      product selectivity for the reverse-water-gas-shift reaction in a fixed-bed flow
      reactor.

PMID- 29205860
TI  - Contrasting patterns of variation in weedy traits and unique crop features in
      divergent populations of US weedy rice (Oryza sativa sp.) in Arkansas and
      California.
AB  - BACKGROUND: Weed evolution from crops involves changes in key traits, but it is
      unclear how genetic and phenotypic variation contribute to weed diversification
      and productivity. Weedy rice is a conspecific weed of rice (Oryza sativa)
      worldwide. We used principal component analysis and hierarchical clustering to
      understand how morphologically and evolutionarily distinct US weedy rice
      populations persist in rice fields in different locations under contrasting
      management regimes. Further, we used a representative subset of 15 sequence
      tagged site fragments of expressed genes from global Oryza to assess genome-wide
      sequence variation among populations. RESULTS: Crop hull color and crop
      overlapping maturity dates plus awns, seed (panicle) shattering (> 50%),
      pigmented pericarp and stature variation (30.2% of total phenotypic variance)
      characterize genetically less diverse California weedy rice. By contrast, wild
      like hull color, seed shattering (> 50%) and stature differences (55.8% of total
      phenotypic variance) typify genetically diverse weedy rice ecotypes in Arkansas.
      CONCLUSION: Recent de-domestication of weedy species - such as in California
      weedy rice - can involve trait combinations indistinguishable from the crop. This
      underscores the need for strict seed certification with genetic monitoring and
      proactive field inspection to prevent proliferation of weedy plant types. In
      established populations, tillage practice may affect weed diversity and
      persistence over time. (c) 2017 Society of Chemical Industry.

PMID- 29205861
TI  - Establishing an indicator rate for computed tomography pulmonary angiography
      positivity (yield) in emergency department pulmonary embolism investigation.

PMID- 29205862
TI  - Determination of the transformation of ginsenosides in Ginseng Radix et Rhizoma
      during decoction with water using ultra-fast liquid chromatography coupled with
      tandem mass spectrometry.
AB  - This study was conducted to determine the variations of ginsenosides in Ginseng
      Radix et Rhizoma when using different preparation solvents and explore the major
      factors for changes. With an established ultra-fast liquid chromatography coupled
      with tandem mass spectrometry method which could quantify 52 ginsenosides, the
      extraction differences were characterized and compared using different solvents
      (water, 70% aqueous ethanol, and ethanol). Subsequently, a series of aqueous
      solutions with different pH were prepared to test the influence of pH to the
      changes of ginsenosides. Meanwhile, acetic acid and aspartic acid were used to
      verify whether the reaction had a relationship with the kind of acids. After
      refluxing with water, not only highly polar ginsenosides were extracted, some
      less polar ginsenosides such as ginsenoside Rg3 , Rg5 , Rk1 , and Rh2 occurred or
      increased rapidly. Further experiments indicated that less polar ginsenosides
      were easier to generate at low pH values, and the reaction was only related to pH
      other than what kind of acids were used. It is the first time to elaborate the
      contents variation of 52 ginsenosides when using different extraction methods.
      The results indicated that decoction with water could enhance the transformation
      of highly polar ginsenosides to less polar ginsenosides and the process was pH
      dependent.

PMID- 29205863
TI  - (-)-Epicatechin and the Colonic 2,3-Dihydroxybenzoic Acid Metabolite Regulate
      Glucose Uptake, Glucose Production, and Improve Insulin Signaling in Renal NRK
      52E Cells.
AB  - SCOPE: (-)-Epicatechin (EC) and main colonic phenolic acids derived from
      flavonoid intake, such as 2,3-dihydroxybenzoic acid (DHBA), 3,4
      dihydroxyphenylacetic acid (DHPAA), 3-hydroxyphenylpropionic acid (HPPA), and
      vanillic acid (VA), have been suggested to exert beneficial effects in diabetes,
      although the mechanism for their actions remains unknown. In this study, the
      modulation of glucose homeostasis and insulin signaling by the mentioned
      compounds on renal proximal tubular NRK-52E cells is investigated. METHODS AND
      RESULTS: Levels of the glucose transporters SGLT-2 and GLUT-2, as well as glucose
      uptake, glucose production, and key proteins of the insulin pathways, namely
      insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and PI3K/AKT pathway
      are analyzed. EC (5-20 MUm) and DHBA (20 MUm) reduced both renal glucose uptake
      and production. Interestingly, EC and DHBA did not modify the levels of SGLT-2
      and GLUT-2, and modulated the expression of phosphoenolpyruvate carboxykinase via
      AKT leading to a diminished glucose production. EC and DHBA also enhanced the
      tyrosine phosphorylation and total IR and IRS-1 levels, and activated the
      PI3K/AKT pathway in NRK-52E cells. CONCLUSION: EC and DHBA regulate the renal
      glucose homeostasis by modulating both glucose uptake and production, and
      strengthen the insulin signaling by activating key proteins of that pathway in
      NRK-52E cells.

PMID- 29205864
TI  - A bifunctional cellulase-xylanase of a new Chryseobacterium strain isolated from
      the dung of a straw-fed cattle.
AB  - A new cellulolytic strain of Chryseobacterium genus was screened from the dung of
      a cattle fed with cereal straw. A putative cellulase gene (cbGH5) belonging to
      glycoside hydrolase family 5 subfamily 46 (GH5_46) was identified and cloned by
      degenerate PCR plus genome walking. The CbGH5 protein was overexpressed in Pichia
      pastoris, purified and characterized. It is the first bifunctional cellulase
      xylanase reported in GH5_46 as well as in Chryseobacterium genus. The enzyme
      showed an endoglucanase activity on carboxymethylcellulose of 3237 MUmol min-1 
      mg-1 at pH 9, 90  degrees C and a xylanase activity on birchwood xylan of 1793
      MUmol min-1  mg-1 at pH 8, 90  degrees C. The activity level and thermophilicity
      are in the front rank of all the known cellulases and xylanases. Core
      hydrophobicity had a positive effect on the thermophilicity of this enzyme. When
      similar quantity of enzymatic activity units was applied on the straws of wheat,
      rice, corn and oilseed rape, CbGH5 could obtain 3.5-5.0* glucose and 1.2-1.8*
      xylose than a mixed commercial cellulase plus xylanase of Novozymes. When applied
      on spent mushroom substrates made from the four straws, CbGH5 could obtain 9.2
      15.7* glucose and 3.5-4.3* xylose than the mixed Novozymes cellulase+xylanase.
      The results suggest that CbGH5 could be a promising candidate for industrial
      lignocellulosic biomass conversion.

PMID- 29205865
TI  - Estimated incidence of influenza-associated severe acute respiratory infections
      in Indonesia, 2013-2016.
AB  - BACKGROUND: Indonesia's hospital-based Severe Acute Respiratory Infection (SARI)
      surveillance system, Surveilans Infeksi Saluran Pernafasan Akut Berat Indonesia
      (SIBI), was established in 2013. While respiratory illnesses such as SARI pose a
      significant problem, there are limited incidence-based data on influenza disease
      burden in Indonesia. This study aimed to estimate the incidence of influenza
      associated SARI in Indonesia during 2013-2016 at three existing SIBI surveillance
      sites. METHODS: From May 2013 to April 2016, inpatients from sentinel hospitals
      in three districts of Indonesia (Gunung Kidul, Balikpapan, Deli Serdang) were
      screened for SARI. Respiratory specimens were collected from eligible inpatients
      and screened for influenza viruses. Annual incidence rates were calculated using
      these SIBI-enrolled influenza-positive SARI cases as a numerator, with a
      denominator catchment population defined through hospital admission survey (HAS)
      to identify respiratory-coded admissions by age to hospitals in the sentinel site
      districts. RESULTS: From May 2013 to April 2016, there were 1527 SARI cases
      enrolled, of whom 1392 (91%) had specimens tested and 199 (14%) were influenza
      positive. The overall estimated annual incidence of influenza-associated SARI
      ranged from 13 to 19 per 100 000 population. Incidence was highest in children
      aged 0-4 years (82-114 per 100 000 population), followed by children 5-14 years
      (22-36 per 100 000 population). CONCLUSIONS: Incidence rates of influenza
      associated SARI in these districts indicate a substantial burden of influenza
      hospitalizations in young children in Indonesia. Further studies are needed to
      examine the influenza burden in other potential risk groups such as pregnant
      women and the elderly.

PMID- 29205867
TI  - Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility
      of Slow-Growing Bacteria.
AB  - Infectious diseases are caused by pathogenic microorganisms and are often severe.
      Time to fully characterize an infectious agent after sampling and to find the
      right antibiotic and dose are important factors in the overall success of a
      patient's treatment. Previous results suggest that a nanomotion detection method
      could be a convenient tool for reducing antibiotic sensitivity characterization
      time to several hours. Here, the application of the method for slow-growing
      bacteria is demonstrated, taking Bordetella pertussis strains as a model. A low
      cost nanomotion device is able to characterize B. pertussis sensitivity against
      specific antibiotics within several hours, instead of days, as it is still the
      case with conventional growth-based techniques. It can discriminate between
      resistant and susceptible B. pertussis strains, based on the changes of the
      sensor's signal before and after the antibiotic addition. Furthermore, minimum
      inhibitory and bactericidal concentrations of clinically applied antibiotics are
      compared using both techniques and the suggested similarity is discussed.

PMID- 29205866
TI  - Clinical features and outcome of lymphoma patients with pre-existing autoimmune
      diseases.
AB  - AIMS: Previous epidemiological studies have shown that autoimmune diseases
      increase the risk of lymphoma development. However, whether autoimmune diseases
      deteriorate the outcomes for lymphoma patients remains unclear. This study aimed
      to identify the clinical features of lymphoma patients with pre-existing
      autoimmune diseases. Whether pre-existing autoimmune diseases impacted
      progression-free survival (PFS) and overall survival (OS) in lymphoma patients
      was further investigated. METHODS: We retrospectively reviewed medical records of
      913 newly diagnosed lymphoma patients from January 2008 to November 2016. Thirty
      four lymphoma patients with pre-existing autoimmune disorders were identified.
      Six of these 34 patients were lost to follow-up; their data was used to examine
      baseline clinical characteristics but not survival. Therefore, 28 lymphoma
      patients with autoimmune diseases were included in the autoimmune disease group
      for comparing the remission rate, PFS and OS to lymphoma patients without
      autoimmune diseases (control group; n = 56). RESULTS: Diffuse large B-cell
      lymphoma was the most common histological subtype (18/34; 52.94%). Complete
      remission rates in the autoimmune disease and control groups were 72.0% and
      83.3%, respectively (P = 0.178). Patients with and without autoimmune diseases
      had similar PFS (45.4 +/- 59.9 months vs. 51.5 +/- 42.8 months; P = 0.398) and OS
      (46.4 +/- 52.6 months vs. 50.1 +/- 47.3 months; P = 0.352). By univariate
      analysis, pre-existing autoimmune diseases were not associated with inferior PFS
      (P = 0.326) or OS (P = 0.627). CONCLUSIONS: Lymphoma patients with and without
      autoimmune disorders had comparable outcomes. Autoimmune diseases are not an
      obstacle to lymphoma treatment.

PMID- 29205868
TI  - Ficoll-hypaque separation vs whole blood lysis: Comparison of efficiency and
      impact on minimal residual disease analysis.
AB  - INTRODUCTION: The high-throughput era remarkably changed molecular laboratory
      practice. Actually, the increasing number of processed samples requires to reduce
      the risk of operator biases, by automating or simplifying as much as possible
      both the analytical and the pre-analytical phases. Minimal residual disease (MRD)
      studies in hematology often require a simultaneous processing of many bone marrow
      and peripheral blood samples from patients enrolled in prospective, multicenter,
      clinical trials, monitored at several planned time points. METHODS: In this
      study, we demonstrate that red blood cell lysis (RBL) pre-analytical procedure
      can replace the time-consuming Ficoll stratification as cell recovering step.
      Here, we show a MRD comparison study using both total white blood cells and
      mononuclear cells recovered by the 2 procedures from 46 follicular lymphoma (FL),
      15 multiple myeloma (MM), and 11 mantle cell lymphoma (MCL) patients enrolled in
      prospective clinical trials. RESULTS: The experiments were performed in the 4
      laboratories of the Fondazione Italiana Linfomi (FIL) MRD Network and showed
      superimposable results, in terms of good correlation (R = 0.87) of the MRD data
      obtained by recovering blood cells by the 2 approaches. CONCLUSION: Based on
      these results, the FIL MRD Network suggests to optimize the pre-analytical phases
      introducing RBL approach for cell recovery in the clinical trials including MRD
      analysis.

PMID- 29205869
TI  - A simple approach to prepare a sulfone-embedded stationary phase for HPLC.
AB  - In the present study, a polar-embedded reversed-phase liquid chromatographic
      stationary phase that contained internal sulfone groups was prepared. The
      synthesis involved the "thiol-ene" click chemistry between the vinyl
      functionalized silica and 1-octadecanethiol, followed by the oxidization of
      sulfide to sulfone groups. The resulting material simultaneously possessed the
      alkyl chain, i.e. C18, and the internal sulfone groups. Elemental analysis
      demonstrates that the element contents of the C18/sulfone silica were C 8.94%, H
      1.87% and S 0.66%. Chromatographic evaluations indicate that the C18/sulfone
      stationary phase exhibited a little less retention than the C18/sulfide one. A
      comparable chromatographic performance of neutral analytes was obtained on these
      two columns, but much better chromatographic performance in the case of basic and
      acid analytes was obtained on C18/sulfone stationary phase with additional
      features such as lower silanol activity, better stability (stable working
      conditions of pH 1.0-10.0), and better compatibility with 100% aqueous mobile
      phases. The batch-to-batch reproducibility was acceptable (the RSDs of retention
      times for the probes were no higher than 1.73%), demonstrating the suitability of
      the applied synthetic strategy for the new stationary phase. The C18/sulfone is a
      promising polar-embedded RPLC stationary phase.

PMID- 29205870
TI  - Therapeutic Thrombocytapheresis for Symptomatic Thrombocytosis in Hemato-Oncology
      Patients.

PMID- 29205871
TI  - Pharmacogenetic Analysis of the Model-Based Pharmacokinetics of Five Anti-HIV
      Drugs: How Does This Influence the Effect of Aging?
AB  - Analysis of aging and pharmacogenetics (PGx) on antiretroviral pharmacokinetics
      (PKs) could inform precision dosing for older human HIV-infected patients.
      Seventy-four participants receiving either atazanavir/ritonavir (ATV/RTV) or
      efavirenz (EFV) with tenofovir/emtricitabine (TFV/FTC) provided PK and PGx
      information. Aging-PGx-PK association and interaction analyses were conducted
      using one-way analysis of variance (ANOVA), multiple linear regression, and
      Random Forest ensemble methods. Our analyses associated unbound ATV disposition
      with multidrug resistance protein (MRP)4, RTV with P-glycoprotein (P-gp), and EFV
      with cytochrome P450 (CYP)2B6 and MRP4 genetic variants. The clearance and
      cellular distribution of TFV were associated with P-gp, MRP2, and concentrative
      nucleoside transporters (CNTs), and FTC parameters were associated with organic
      cation transporters (OCTs) and MRP2 genetic variants. Notably, p16INK4a
      expression, a cellular aging marker, predicted EFV and FTC PK when genetic
      factors were adjusted. Both age and p16INK4a expression interacted with PGx on
      ATV and TFV disposition, implying potential dose adjustment based on aging may
      depend on genetic background.

PMID- 29205873
TI  - Evaluation of Dry Eye Using Anterior Segment Optical Coherence Tomography in
      Patients With End-Stage Renal Disease Undergoing Hemodialysis.
AB  - The aim of the present study was to evaluate dry eye parameters with conventional
      tests and tear meniscus with Anterior Segment Optical Coherence Tomography (AS
      OCT) in patients with end-stage renal disease (ESRD). Thirty-eight ESRD patients
      undergoing hemodialysis, and 40 healthy individuals were enrolled. An ocular
      surface disease index questionnaire (OSDI) was administered. Before conventional
      dry eye tests, tear meniscus were evaluated using AS-OCT. After a complete ocular
      examination, Schirmer and break-up time (BUT) tests were performed and probable
      corneal staining was investigated. Schirmer test and BUT values were
      significantly lower in ESRD patients (P < 0.05). OSDI scores and corneal staining
      scores were significantly higher in ESRD patients (P < 0.05). Tear meniscus
      height, tear meniscus depth, and tear meniscus area, which were obtained by AS
      OCT were significantly lower in patients with ESRD (P < 0.05). Tear meniscus
      evaluation using AS-OCT is an effective and non-invasive method to assess tear
      meniscus in patients with ESRD. Patients with ESRD undergoing hemodialysis should
      obtain regular ophthalmic examination, especially for dry eye.

PMID- 29205874
TI  - Establishment of experimental autoimmune prostatitis model by T2 peptide in
      aluminium hydroxide adjuvant.
AB  - A mouse model was developed to simulate the clinical features of chronic
      prostatitis/chronic pelvic pain syndrome using peptide (T2 ). Forty C57BL/6 mice
      were divided into four groups of 10 mice each, averagely and randomly. T2 plus
      aluminium hydroxide adjuvant group was given subcutaneous injection with the
      emulsion mixture of T2 and aluminium hydroxide adjuvant, the T2 group with T2 ,
      the aluminium hydroxide adjuvant group with aluminium hydroxide adjuvant and the
      normal control group with 0.9/% NaCl solution. Haematoxylin andeosin staining was
      used to observe the inflammation of the prostate. Plasma levels of TNF-alpha and
      CRP were detected by ELISA kit. The expression of IL-1betain the prostate was
      investigated by immunohistochemistry. The statistical differences between the
      groups were compared by t test. Histopathological analyses demonstrated that
      prostate lesions were most severe in the group immunised with T2 plus aluminium
      hydroxide adjuvant. Plasma levels of TNF-alpha and CRP were statistically
      elevated compared with control groups. The expression levels of IL-1beta in the
      prostate were more obvious than control groups. T2 in aluminium hydroxide
      adjuvant subcutaneous injection could successfully set up experimental autoimmune
      prostatitis in C57BL/6 mice. This murine model would be greatly beneficial to
      further comprehend the aetiology, pathogenesis and explicit treatment of CP/CPPS.

PMID- 29205875
TI  - A case report of basic calcium phosphate deposition disease mimicking septic
      arthritis.
AB  - We report a case of a 53-year-old man who presented with a diagnostic dilemma
      mimicking septic arthritis. It is important to consider the diagnosis of calcific
      peri-arthritis clinically and recognize the hallmarks on radiograph and magnetic
      resonance imaging as this disease process resolves completely with conservative
      management like in our patient, and does not require operative intervention.

PMID- 29205876
TI  - Vitamin D Does Not Play a Functional Role in Adipose Tissue Development in Rodent
      Models.
AB  - SCOPE: Several studies have proposed a role of vitamin D in adipogenesis. Here,
      we sought to study the impact of the vitamin D receptor (Vdr) on adipocyte size
      in young and old mice and the effect of maternal vitamin D deficiency on fetal
      adipogenesis. METHODS AND RESULTS: Histological analysis of adipose tissues shows
      that Vdr knockout (KO) mice have smaller adipocytes than wild-type (WT) mice.
      Next, we compare young and old Vdr-KO and WT mice and find no differences in
      adipocyte sizes between weaned Vdr-KO and WT mice. However, 1-year-old Vdr-KO
      mice, suffering from alopecia, have smaller-sized adipocytes than WT mice,
      although they consume more food. To elucidate whether vitamin D can directly
      impact adipocyte development at a critical stage of adipogenesis, we feed rat
      dams a vitamin D deficient (0 IU kg-1 ) or vitamin D adequate (1000 IU kg-1 )
      diet. Neither DNA microarray analysis of the adipose tissues of the newborn rats
      nor the adipocyte sizes of 21-day-old offspring show significant differences
      between the two groups. CONCLUSION: Data indicate that vitamin D does not play a
      fundamental role in adipogenesis because vitamin D does not affect fetal
      adipogenesis. Moreover, the smaller adipocytes observed in adult Vdr-KO mice are
      presumably caused by an increased energy expenditure due to alopecia.

PMID- 29205877
TI  - Molecular epidemiology of Mycobacterium tuberculosis complex strains isolated
      from livestock and wild animals in Italy suggests the need for a different
      eradication strategy for bovine tuberculosis.
AB  - Bovine tuberculosis (bTB) is an important zoonosis, which has been re-emerging in
      different ecological scenarios. In Sicily, Italy, from 2004 to 2014, an
      anatomopathological survey for tuberculosis-like lesions both in farmed and wild
      animals was performed. The isolates were genotyped using spoligotyping and
      Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats
      (MIRU-VNTR) techniques. High prevalence of lesions was observed for cattle (4%),
      pigs (4.9%) and wild boars (6.8%), and a total of 625 Mycobacterium bovis
      isolates were identified. Genotyping analysis showed the presence of 37 different
      spoligotypes including fifteen spoligotypes not present in other Italian regions
      and 266 MIRU-VNTR profiles. Spoligotype SB0120 exhibited the highest prevalence
      in cattle (50%) and pigs (56%) and the highest genetic variety with 126 different
      MIRU-VNTR profiles. The isolation of M. bovis in a farmer underlines the
      importance of M. bovis identification during the human TB diagnostic processes.
      This study supported the use of the genotyping analysis as a valuable tool for
      the evaluation of the epidemiological role of pigs and other domestic reservoirs
      such as goats and the role of wildlife in the maintenance of bTB infection.

PMID- 29205878
TI  - Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell
      Capture and Targeted siRNA Delivery.
AB  - Instability and poor targeting causes the long-term patency of RNA-modified
      tissue engineering blood vessels (TEBVs) remaining unsatisfactory. RNA can be
      enriched in exosome and then delivered into targeted cells while whether exosome
      modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the
      expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes,
      klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA
      is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection.
      Flow chamber results show that klotho/ADK siRNA-exosome can effectively capture
      circulating endothelial progenitor cells (EPCs). Besides, the captured EPCs can
      endocytose this exosome, and then decompose it into klotho protein and ADK siRNA.
      Moreover, ADK siRNA promotes the paracrine of proangiogenic factors and adenosine
      from EPCs, which further facilitate proliferation and migration of endothelial
      cells. Based on polyethyleneimine-capped gold nanoparticles, exosome-modified
      TEBVs are constructed through layer-by-layer assembly. Animal experimental
      results show that klotho/ADK siRNA-exosome-modified TEBVs can maintain the
      patency up to one month, and good endothelialization is observed. In short, one
      exosome-modified TEBV is constructed, capture molecules on the surface of exosome
      capture the circulating EPCs, and the loaded RNA achieves its purpose of accurate
      treatment depending on the needs of patients.

PMID- 29205879
TI  - Solid-State Diffusional Behaviors of Functional Metal Oxides at Atomic Scale.
AB  - Metal/metal oxides have attracted extensive research interest because of their
      combination of functional properties and compatibility with industry. Diffusion
      and thermal reliability have become essential issues that require detailed study
      to develop atomic-scaled functional devices. In this work, the diffusional
      reaction behavior that transforms piezoelectric ZnO into magnetic Fe3 O4 is
      investigated at the atomic scale. The growth kinetics of metal oxides are
      systematically studied through macro- and microanalyses. The growth rates are
      evaluated by morphology changes, which determine whether the growth behavior was
      a diffusion- or reaction-controlled process. Furthermore, atom attachment on the
      kink step is observed at the atomic scale, which has important implications for
      the thermodynamics of functional metal oxides. Faster growth planes
      simultaneously decrease, which result in the predominance of low surface energy
      planes. These results directly reveal the atomic formation process of metal oxide
      via solid-state diffusion. In addition, the nanofabricated method provides a
      novel approach to investigate metal oxide evolution and sheds light on
      diffusional reaction behavior. More importantly, the results and phenomena of
      this study provide considerable inspiration to enhance the material stability and
      reliability of metal/oxide-based devices.

PMID- 29205880
TI  - Intrapulmonary teratoma misdiagnosed as aspergilloma.

PMID- 29205881
TI  - Corrigendum.

PMID- 29205882
TI  - Estimating the burden of influenza-associated hospitalization and deaths in Oman
      (2012-2015).
AB  - BACKGROUND: Influenza is a serious vaccine-preventable disease with high
      incidence, hospitalization, and mortality in high-risk groups. The epidemiology,
      seasonality, and risk factors for influenza are well defined in most of the
      temperate countries, but estimating influenza burden in the World Health
      Organization (WHO) Region for the Eastern Mediterranean is scarce. In Oman,
      despite the advancements in influenza surveillance, the clinical burden and
      seasonality of influenza remain not fully understood. OBJECTIVES: To estimate the
      incidence of influenza-associated hospitalizations and in-hospital death in Oman.
      PATIENTS AND METHODS: Influenza-associated hospitalizations and in-hospital
      deaths were estimated using hospital discharge records based on ICD-10 codes (J09
      J18), results of virological analysis and population census for the period
      between 2012 and 2015. RESULTS: During 2012 and 2015, we identified a total of 19
      405 influenza-associated hospitalization and 847 deaths. Influenza positivity
      percentage ranged from 6.4% in 2013 to 20.6% in 2015. Influenza-associated
      hospitalization incidence rate was 7.3 (95% CI: 6.4-8.1) per 100 000 in 2013 and
      27.5 (95% CI: 25.9-29.1) per 100 000 in 2015 with an overall rate of 20.6 (95%
      CI: 19.9-21.3) per 100 000. The highest incidence of influenza-associated death
      was among those aged >=65 years and ranged between 39.5 (95% CI: 27.3-51.8) per
      100 000 in 2014 and 11.3 (95% CI: 7.5-15.1) in 2015. CONCLUSIONS: Influenza
      causes a substantial number of hospitalizations and deaths in Oman.
      Hospitalization rates were highest among children, and adults >=65 years showed
      the highest death rate. The potential value of using seasonal influenza vaccine
      in these groups should be considered.

PMID- 29205883
TI  - Fission yeast Myo2: Molecular organization and diffusion in the cytoplasm.
AB  - Myosin-II is required for the assembly and constriction of cytokinetic
      contractile rings in fungi and animals. We used electron microscopy, fluorescence
      recovery after photobleaching (FRAP), and fluorescence correlation spectroscopy
      (FCS) to characterize the physical properties of Myo2 from fission yeast
      Schizosaccharomyces pombe. By electron microscopy, Myo2 has two heads and a
      coiled-coiled tail like myosin-II from other species. The first 65 nm of the tail
      is a stiff rod, followed by a flexible, less-ordered region up to 30 nm long.
      Myo2 sediments as a 7 S molecule in high salt, but aggregates rather than forming
      minifilaments at lower salt concentrations; this is unaffected by heavy chain
      phosphorylation. We used FRAP and FCS to observe the dynamics of Myo2 in live S.
      pombe cells and in cell extracts at different salt concentrations; both show that
      Myo2 with an N-terminal mEGFP tag has a diffusion coefficient of ~ 3 um2 s-1 in
      the cytoplasm of live cells during interphase and mitosis. Photon counting
      histogram analysis of the FCS data confirmed that Myo2 diffuses as doubled-headed
      molecules in the cytoplasm. FCS measurements on diluted cell extracts showed that
      mEGFP-Myo2 has a diffusion coefficient of ~ 30 um2 s-1 in 50 to 400 mM KCl
      concentrations.

PMID- 29205885
TI  - Label-free imaging and spectroscopy for early detection of cervical cancer.
AB  - The label-free imaging and spectroscopy method was studied on cervical unstained
      tissue sections obtained from 36 patients. The native fluorescence spectra of
      tissues are analyzed by the optical redox ratio (ORR), which is defined as
      fluorescence intensity ratio between NADH and FAD, and indicates the metabolism
      change with the cancer development. The ORRs of normal tissues are consistently
      higher than those of precancer or cancerous tissues. A criterion line of ORR at
      5.0 can be used to discriminate cervical precancer/cancer from normal tissues.
      The sensitivity and specificity of the native fluorescence spectroscopy method
      for cervical cancer diagnosis are determined as 100% and 91%. Moreover, the
      native fluorescence spectroscopy study is much more sensitive on the healthy
      region of cervical precancer/cancer patients compared with the traditional
      clinical staining method. The results suggest label-free imaging and spectroscopy
      is a fast, highly sensitive and specific method on the detection of cervical
      cancer.

PMID- 29205884
TI  - Potential Adult Neurogenesis in the Telencephalon and Cerebellar Cortex of the
      Nile Crocodile Revealed with Doublecortin Immunohistochemistry.
AB  - The brain of the crocodile is known to gain in mass allometrically throughout
      life, and the addition of neurons (as well as non-neurons) appears to play a
      significant role in this increasing brain mass. We used immunohistochemistry in
      the brains of 12 Nile crocodiles ranging between 350 g and 86 kg in body mass and
      1.99 g to 7.9 g in brain mass to identify the regions of the brain in which
      neurons immunopositive for doublecortin (DCX), a marker for potential adult
      neurogenesis, are found. Similar to other reptiles, potential newly born neurons,
      those immunopositive for DCX, were found throughout the telencephalon, the main
      and accessory olfactory bulbs and the olfactory tract, and in the cerebellar
      cortex; however, no DCX immunopositive neurons were observed in the diencephalon
      or brainstem. An apparent moderate decrease in the density of DCX labeled neurons
      in the olfactory bulbs and tract as well as the cerebellar cortex was observed
      with increasing brain mass, but the observed qualitative density of labeled
      neurons within the telencephalon was maintained irrespective of brain mass. Three
      potential neurogenic zones, within the sulci of the lateral ventricle, were
      identified, and these are similar to those seen in other reptiles. This study
      indicates that at least part of the gain in brain mass with age in the Nile
      crocodile may be accounted for by the potential addition and integration of new
      neurons into the existing circuitry, especially so for the olfactory system,
      telencephalon and cerebellar cortex. Anat Rec, 301:659-672, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29205886
TI  - Ambulatory central VA-ECMO with biventricular decompression for acute cardiogenic
      shock.
AB  - We describe the off-pump insertion of a biventricular assist device with extra
      corporeal membrane oxygenation (ECMO): a novel technique that allows for
      ambulatory central veno-arterial (VA) ECMO with direct biventricular
      decompression.

PMID- 29205887
TI  - Role, ownership and presence of domestic animals in peri-urban households of
      Kisumu, Kenya.
AB  - Low- and middle-income countries are experiencing rapid urban population growth,
      particularly in peri-urban informal settlements. In these urban areas, animal
      husbandry remains a valuable source of income and protein-rich foods but may also
      present a risk of zoonotic disease threat. To date, there have been studies that
      have assessed the prevalence and nature of animal ownership in these communities.
      This cross-sectional survey assessed the geographical, sociocultural and economic
      factors behind the presence, ownership and purpose of domestic animals in three
      informal peri-urban communities of Kisumu, Kenya. A majority (n = 587) of the
      study households exhibited domestic animal presence in the living space yet only
      32% of households reported animal ownership (n = 252). The purposes of ownership
      included: for meat/eggs (55%); for income, sale or trade (43%); for milk
      production (31%); and as companions/pets (31%). Among households that owned
      animals, 76% reported that at least one animal slept in the house at night. In
      multivariate logistic regression, the following factors were significantly
      associated with household animal ownership: ownership of agricultural land (OR =
      1.94, 95% CI = 1.12, 3.35), perceiving a strong community bond (OR = 2.28, 95% CI
      = 1.25, 4.16), and household membership in a community group (OR = 1.64, 95% CI =
      1.04, 2.60). This research demonstrates the high prevalence of animal ownership
      in a low-income and high-density peri-urban neighbourhood of an African city,
      which may facilitate zoonotic disease transmission. Further research should
      assess if and to what extent animal ownership in such communities is associated
      with disease risk.

PMID- 29205891
TI  - The ISFA wishes to acknowledge the following 2017 Corporate Sponsors.

PMID- 29205888
TI  - Glomerular Filtration Rate and Initiation of Dialysis.
AB  - The proportion of patients with advanced chronic kidney disease (CKD) initiating
      dialysis at higher glomerular filtration rate (GFR) has increased over the past
      decade. Recent data suggest that it may be associated with increased mortality.
      The goal of this analysis was to compare survival outcomes in patients with early
      and late start dialysis. We performed a retrospective analysis of hemodialysis
      (HD) incident patients from 1 January 2010 to 30 September 2014. Patients were
      classified into two groups by estimated GFR at dialysis initiation (eGFR >=10:
      early start and <10 mL/min per 1.73m2 : late start). Logistic regression was used
      to evaluate factors associated with early and late dialysis start, and Kaplan
      Meier graphs and Cox regression models in survival analysis. In this total
      incident population (N = 235), 42 patients had an early dialysis start. Compared
      with the group with an eGFR of <10 mL/min per 1.73 m2 at dialysis start, a Cox
      model showed an incremental increase in mortality associated with earlier
      dialysis start (P = 0.027). Independent factors (P < 0.05) associated with
      mortality in the multivariable Cox model in early dialysis start were:
      hypertension (HR 9.32, CI: 1.34-17.87), diabetes (HR 1.8, CI: 0.4-13.2) and
      albumin <3.5 g/dL (HR 1.5, CI: 0.8-6.2). Older patients (HR 0.084, CI: 0.008
      0.863) with low phosphorus levels (HR 0.02, CI: 0.0-0.527) also had statistically
      significant results, although they showed a reduced risk of mortality. Early
      dialysis initiation was associated with an increased mortality risk, arguing
      against aggressive early dialysis initiation based primarily on eGFR alone.

PMID- 29205892
TI  - Biological Agents and Therapeutic Plasma Exchange: Can They Coexist in the
      Future?

PMID- 29205893
TI  - Measuring the gut microbiome in birds: Comparison of faecal and cloacal sampling.
AB  - The gut microbiomes of birds and other animals are increasingly being studied in
      ecological and evolutionary contexts. Numerous studies on birds and reptiles have
      made inferences about gut microbiota using cloacal sampling; however, it is not
      known whether the bacterial community of the cloaca provides an accurate
      representation of the gut microbiome. We examined the accuracy with which cloacal
      swabs and faecal samples measure the microbiota in three different parts of the
      gastrointestinal tract (ileum, caecum, and colon) using a case study on juvenile
      ostriches, Struthio camelus, and high-throughput 16S rRNA sequencing. We found
      that faeces were significantly better than cloacal swabs in representing the
      bacterial community of the colon. Cloacal samples had a higher abundance of
      Gammaproteobacteria and fewer Clostridia relative to the gut and faecal samples.
      However, both faecal and cloacal samples were poor representatives of the
      microbial communities in the caecum and ileum. Furthermore, the accuracy of each
      sampling method in measuring the abundance of different bacterial taxa was highly
      variable: Bacteroidetes was the most highly correlated phylum between all three
      gut sections and both methods, whereas Actinobacteria, for example, was only
      strongly correlated between faecal and colon samples. Based on our results, we
      recommend sampling faeces, whenever possible, as this sample type provides the
      most accurate assessment of the colon microbiome. The fact that neither sampling
      technique accurately portrayed the bacterial community of the ileum nor the
      caecum illustrates the difficulty in noninvasively monitoring gut bacteria
      located further up in the gastrointestinal tract. These results have important
      implications for the interpretation of avian gut microbiome studies.

PMID- 29205895
TI  - Arterial distribution to the pelvic cavity and pelvic limb in the pampas deer
      (Ozotoceros bezoarticus, Linnaeus 1758).
AB  - This research is a study about the arterial vascularization of pelvic cavity and
      pelvic limb in pampas deer. For this study, 25 dead animals were used. The
      vascularization of the organs was investigated using a latex injection technique.
      Two animals were injected in the common carotid artery with contrast to cardiac
      angiography, and then, radiographs were taken. The aorta showed the two external
      iliac arteries, and after a short course, the aorta ended in two internal iliac
      arteries. The median sacral artery was originated from the dorsal surface
      cranially to the emergence of the internal iliac arteries. The last one gave off
      parietal (iliolumbar, cranial and caudal gluteal arteries) and visceral
      (umbilical and internal pudendal arteries) branches. The external iliac artery
      gave as first branch the deep circumflex iliac artery which was divided into a
      cranial and a caudal branch. After a short distance from the external iliac
      artery, the femoral and deep femoral arteries were originated. The deep femoral
      artery gave origin to the pudendoepigastric trunk and to the medial femoral
      circumflex artery. Based on the arterial distribution of the pelvic cavity and
      pelvic limb in the pampas deer, it is concluded that the internal iliac artery
      has a pattern of intermediate development. In reference to the distribution of
      the external iliac artery and its branches, the pattern of development is the
      cranial tibial type.

PMID- 29205894
TI  - Association of angiotensin-converting enzyme insertion/deletion polymorphism with
      susceptibility to systemic lupus erythematosus: a meta-analysis.
AB  - BACKGROUND: The aim of this study was to determine whether the angiotensin
      converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism confers
      susceptibility to systemic lupus erythematosus (SLE)/lupus nephritis (LN).
      METHODS: A meta-analysis was conducted on the association between the ACE I/D
      polymorphism and SLE/LN (when available) using: (i) the allelic contrast; (ii)
      the recessive; (iii) the dominant; and (iv) the additive models. RESULTS: A total
      of 27 relevant comparisons meeting the inclusion criteria were identified,
      involving 2718 SLE patients and 3655 controls. Meta-analysis showed a significant
      association between SLE and the allele D in overall populations (odds ratio [OR]
      = 1.25, 95% CI: 1.07-1.48, P = 0.004). Stratification by ethnicity indicated a
      strong association between the allele D and SLE in Asians (OR = 1.36, 95% CI:
      1.05-1.75, P = 0.019). Meta-analysis also showed a significant association
      between SLE and the DD genotype in overall populations (additive model) (OR =
      1.38, 95% CI: 1.05-1.83, P = 0.022). In addition, we found significant
      associations between the recessive model and SLE in overall populations, Asians
      and Europeans (OR = 1.44, 95% CI: 1.11-1.88, P = 0.007; OR = 1.69, 95% CI: 1.07
      2.68, P = 0.024; and OR = 1.31, 95% CI: 1.06-1.62, P = 0.013, respectively). With
      respect to the association between ACE I/D gene polymorphism and LN risk, there
      was no significant association in either the overall populations or
      subpopulations. CONCLUSION: The present study might suggest that ACE I/D
      polymorphism may be a genetic molecular marker to predict SLE, while this
      polymorphism may not correlate with LN susceptibility.

PMID- 29205896
TI  - Paracoccidioidomycosis ceti in an Atlantic bottlenose dolphin (Tursiops
      truncatus), Brazil.

PMID- 29205897
TI  - Chiral separation of disease biomarkers with 2-hydroxycarboxylic acid structure.
AB  - Chiral 2-hydroxycarboxylic acids are compounds that have been linked to
      particular diseases and are putative biomarkers with some diagnostic potential.
      The importance of identifying whether a particular enantiomer is related to
      certain diseases has been encouraged recently. However, in many cases it has not
      yet been elucidated whether there are stereochemical implications with respect to
      these biomarkers and whether their enantioselective analysis provides new
      insights and diagnostic potential. In this study 13 disease-related chiral 2
      hydrocarboxylic acids were studied for their chiral separation by high
      performance liquid chromatography on three cinchona alkaloid-derived chiral
      stationary phases. From a subgroup of eight 2-hydroxymonocarboxylic acids,
      baseline resolution could be achieved and inversion of elution order by
      exchanging tert-butylcarbamoyl quinidine chiral stationary phase (Chiralpak QD
      AX) for the corresponding quinine analogue (Chiralpak QN-AX) is shown for seven
      of them. Furthermore, conditions for chiral separation of the 2
      hydroxydicarboxylic acids, citramalic acid, 2-isopropylmalic acid, and 2
      hydroxyadipic acid are reported and compared to the previous reported conditions
      for 2-hydroxyglutaric acid and malic acid.

PMID- 29205898
TI  - Effects of oral glucosamine hydrochloride and mucopolysaccharide protein in a
      rabbit model of osteoarthritis.
AB  - AIM: The aim was to study whether oral glucosamine hydrochloride (GlcN.HCl) or
      mucopolysaccharide protein (MucoP) has a structure-modifying effect on an
      anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis
      (OA). METHODS: OA was surgically induced in the right knees of rabbits by
      transection of the ACLT. The left knees served as a sham-operated control. The
      animals were divided into four groups (n = 6 each): negative control (phosphate
      buffered saline, orally), positive control (oral celecoxib 10 mg/kg body
      weight/day), GlcN.HCl (oral 100 mg/kg/day) and MucoP (oral 100 mg/kg/day).
      Experimental animals were sacrificed after 8 weeks of treatment and the distal
      femur was removed for macroscopic examination, histological assessment, and
      terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay of
      the OA rabbits. RESULTS: On gross morphology, severe lesions were observed in
      articular cartilage in the negative control group. In the GlcN.HCl and MucoP
      treatment groups, fibrillations and cartilaginous lesions were significantly (P <
      0.05) decreased compared to the negative control group. In particular,
      degenerative changes in cartilage and chondrocyte cellularity were significantly
      reduced (P < 0.05) in the positive control (celecoxib) group, GlcN.HCl treatment
      group and MucoP treatment group compared with the negative control group. TUNEL
      assay showed that apoptotic chondrocytes were significantly suppressed in the
      celecoxib group. Similar significant (P < 0.05) results were seen in the GlcN.HCl
      group and MucoP group but apoptosis of chondrocytes were high in the negative
      control group. CONCLUSION: These data suggest that the protective effects of
      GlcN.HCl and MucoP may play a useful role in the clinical treatment of OA.

PMID- 29205899
TI  - Systematic Review: Impact of point sources on antibiotic-resistant bacteria in
      the natural environment.
AB  - Point sources such as wastewater treatment plants and agricultural facilities may
      have a role in the dissemination of antibiotic-resistant bacteria (ARB) and
      antibiotic resistance genes (ARG). To analyse the evidence for increases in ARB
      in the natural environment associated with these point sources of ARB and ARG, we
      conducted a systematic review. We evaluated 5,247 records retrieved through
      database searches, including both studies that ascertained ARG and ARB outcomes.
      All studies were subjected to a screening process to assess relevance to the
      question and methodology to address our review question. A risk of bias
      assessment was conducted upon the final pool of studies included in the review.
      This article summarizes the evidence only for those studies with ARB outcomes (n
      = 47). Thirty-five studies were at high (n = 11) or at unclear (n = 24) risk of
      bias in the estimation of source effects due to lack of information and/or
      failure to control for confounders. Statistical analysis was used in ten studies,
      of which one assessed the effect of multiple sources using modelling approaches;
      none reported effect measures. Most studies reported higher ARB prevalence or
      concentration downstream/near the source. However, this evidence was primarily
      descriptive and it could not be concluded that there is a clear impact of point
      sources on increases in ARB in the environment. To quantify increases in ARB in
      the environment due to specific point sources, there is a need for studies that
      stress study design, control of biases and analytical tools to provide effect
      measure estimates.

PMID- 29205900
TI  - Biophotonics in China.
AB  - Biophotonics is a highly interdisciplinary field where physicists, chemists,
      biologists, physicians and engineers work together to solve the problems
      appearing in biology and medicine. In China, the Biophotonics discipline is often
      referred to as Biomedical Photonics, under the first-level disciplines Biomedical
      Engineering or Optical Engineering, and was initiated in the late 1990s. Over the
      past 20 years, biophotonics research in China expanded extraordinarily and has
      reached the frontiers of the world-level sciences. This white paper introduces
      the research groups in the biophotonics field in China, and their representative
      contributions.

PMID- 29205901
TI  - Dissecting the role of sessional anatomy teachers: A systematic literature
      review.
AB  - Worldwide there is a growing reliance on sessional teachers in universities. This
      has impacted all disciplines in higher education including medical anatomy
      programs. The objective of this review was to define the role and support needs
      of sessional anatomy teachers by reporting on the (1) qualifications, (2)
      teaching role, (3) training, and (4) performance management of this group of
      educators. A systematic literature search was conducted on the 27 July 2017 in
      Scopus, Web of Science, and several databases on the Ovid, ProQuest and EBSCOhost
      platforms. The search retrieved 5,658 articles, with 39 deemed eligible for
      inclusion. The qualifications and educational distance between sessional anatomy
      teachers and their students varied widely. Reports of cross-level, near-peer and
      reciprocal-peer teaching were identified, with most institutes utilizing recent
      medical graduates or medical students as sessional teachers. Sessional anatomy
      teachers were engaged in the full spectrum of teaching-related duties from
      assisting students with cadaveric dissection, to marking student assessments and
      developing course materials. Fourteen institutes reported that training was
      provided to sessional anatomy teachers, but the specific content, objectives,
      methods and effectiveness of the training programs were rarely defined.
      Evaluations of sessional anatomy teacher performance primarily relied on
      subjective feedback measures such as student surveys (n = 18) or teacher self
      assessment (n = 3). The results of this systematic review highlight the need for
      rigorous explorations of the use of sessional anatomy teachers in medical
      education, and the development of evidence-based policies and training programs
      that regulate and support the use of sessional teachers in higher education. Anat
      Sci Educ 11: 410-426. (c) 2017 American Association of Anatomists.

PMID- 29205902
TI  - Therapeutic options and postoperative wound complications after extremity soft
      tissue sarcoma resection and postoperative external beam radiotherapy.
AB  - Soft tissue sarcomas occur most commonly in the lower and upper extremities. The
      standard treatment is limb salvage surgery combined with radiotherapy.
      Postoperative radiotherapy is associated with wound complications. This
      systematic review aims to summarise the available evidence and review the
      literature of the last 10 years regarding postoperative wound complications in
      patients who had limb salvage surgical excision followed by direct closure vs
      flap coverage together with postoperative radiotherapy and to define the optimal
      timeframe for adjuvant radiotherapy after soft tissue sarcomas resection and flap
      reconstruction. A literature search was performed using PubMed. The following
      keywords were searched: limb salvage, limb-sparing, flaps, radiation therapy,
      radiation, irradiation, adjuvant radiotherapy, postoperative radiotherapy,
      radiation effects, wound healing, surgical wound infection, surgical wound
      dehiscence, wound healing, soft tissue sarcoma and neoplasms. In total, 1045
      papers were retrieved. Thirty-seven articles were finally selected after
      screening of abstracts and applying dates and language filters and inclusion and
      exclusion criteria. Plastic surgery provides a vast number of reconstructive flap
      procedures that are directly linked to decreasing wound complications, especially
      with the expectant postoperative radiotherapy. This adjuvant radiotherapy is
      better administered in the first 3-6 weeks after reconstruction to allow timely
      wound healing and avoid local recurrence.

PMID- 29205903
TI  - Transduction Methods for Cytosolic Delivery of Proteins and Bioconjugates into
      Living Cells.
AB  - The human organism and its constituting cells rely on interplay between multiple
      proteins exerting specific functions. Progress in molecular biotechnologies has
      facilitated the production of recombinant proteins. When administrated to
      patients, recombinant proteins can provide important healthcare benefits. To
      date, most therapeutic proteins must act from the extracellular environment, with
      their targets being secreted modulators or extracellular receptors. This is
      because proteins cannot passively diffuse across the plasma membrane into the
      cytosol. To expand the scope of action of proteins for cytosolic targets
      (representing more than 40% of the genome) effective methods assisting protein
      cytosolic entry are being developed. To date, direct protein delivery is
      extremely tedious and inefficient in cultured cells, even more so in animal
      models of pathology. Novel techniques are changing this limitation, as recently
      developed in vitro methods can robustly convey large amount of proteins into cell
      cultures. Moreover, advances in protein formulation or protein conjugates are
      slowly, but surely demonstrating efficiency for targeted cytosolic entry of
      functional protein in vivo in tumor xenograft models. In this review, various
      methods and recently developed techniques for protein transport into cells are
      summarized. They are put into perspective to address the challenges encountered
      during delivery.

PMID- 29205905
TI  - A Simple Modification Method to Obtain Anisotropic and Porous 3D Microfibrillar
      Scaffolds for Surgical and Biomedical Applications.
AB  - In native tissues, cellular organization is predominantly anisotropic. Yet, it
      remains a challenge to engineer anisotropic scaffolds that promote anisotropic
      cellular organization at macroscopic length scales. To overcome this challenge,
      an innovative, cheap and easy method to align clinically approved non-woven
      surgical microfibrillar scaffolds is presented. The method involves a three-step
      process of coating, unidirectional stretching of scaffolds after heating them
      above glass transition temperature, and cooling back to room temperature.
      Briefly, a polymer coating is applied to a non-woven mesh that results in a
      partial welding of randomly oriented microfibers at their intersection points.
      The coated scaffold is then heated above the glass transition temperature of the
      coating and the scaffold polymer. Subsequently, the coated scaffold is stretched
      to produce aligned and three dimentional (3D) porous fibrillar scaffolds. In a
      proof of concept study, a polyglycolic acid (PGA) micro-fibrillar scaffold was
      coated with poly(4-hydroxybutirate) (P4HB) acid and subsequently aligned.
      Fibroblasts were cultured in vitro within the scaffold and results showed an
      increase in cellular alignment along the direction of the PGA fibers. This method
      can be scaled up easily for industrial production of polymeric meshes or directly
      applied to small pieces of scaffolds at the point of care.

PMID- 29205904
TI  - Dosing down and then discontinuing biologic therapy in rheumatoid arthritis: a
      review of the literature.
AB  - AIM: To review the published studies that dose down and then discontinue biologic
      therapy in patients with rheumatoid arthritis (RA), particularly concerning the
      criteria for such dosing and the impact on clinical outcomes. METHODS: Published
      studies conducted in patients with RA that sequentially decreased the dose and
      then discontinued therapy were included if one or more of the following biologic
      disease modifying antirheumatic drugs (bDMARDs) was evaluated: abatacept,
      adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab or
      tocilizumab. RESULTS: Five studies qualified for inclusion. The populations of
      patients with RA were heterogeneous among the studies; patients were required to
      have low disease activity (LDA) or to be in remission prior to dose titration.
      Approximately 25-65% of patients successfully decreased and in some cases,
      discontinued the bDMARD. However, the flare rate was higher than for the patients
      who remained on a standard dose. The only variable that predicted relapse in more
      than one study was down-titration of the bDMARD dose. CONCLUSION: In patients who
      have achieved LDA or remission, down-titration and discontinuation of bDMARD
      therapy may be attempted, with careful monitoring. However, it is likely that
      some patients will flare, and it is not known how to predict these patients.

PMID- 29205906
TI  - The race for antimicrobials in the multidrug resistance era.
AB  - The appearance of multidrug-resistant pathogens is a major threat to human health
      with the reemergence of fatal and untreatable diseases. In addition to a rational
      use of the well-known and available antibiotics, two complementary ways to
      overcome this public health issue are (i) the discovery of new antimicrobials and
      (ii) the chemical modification of pre-existing potent antibiotics. In this
      article, we highlight some of the strategies to generate new and promising
      antimicrobials for use in the management of these so-called 'superbugs'.

PMID- 29205908
TI  - Trace quantification of selected sulfonamides in aqueous media by implementation
      of a new dispersive solid-phase extraction method using a nanomagnetic titanium
      dioxide graphene-based sorbent and HPLC-UV.
AB  - Herein, a new dispersive solid-phase extraction method using a nano magnetic
      titanium dioxide graphene-based sorbent in conjunction with high-performance
      liquid chromatography and ultraviolet detection was successfully developed. The
      method was proved to be simple, sensitive, and highly efficient for the trace
      quantification of sulfacetamide, sulfathiazole, sulfamethoxazole, and
      sulfadiazine in relatively large volume of aqueous media. Initially, the nano
      magnetic titanium dioxide graphene-based sorbent was successfully synthesized and
      subsequently characterized by scanning electron microscopy and X-ray diffraction.
      Then, the sorbent was used for the sorption and extraction of the selected
      sulfonamides mainly through pi-pi stacking hydrophobic interactions. Under the
      established conditions, the calibration curves were linear over the concentration
      range of 1-200 MUg/L. The limit of quantification (precision of 20%, and accuracy
      of 80-120%) for the detection of each sulfonamide by the proposed method was 1.0
      MUg/L. To test the extraction efficiency, the method was applied to various
      fortified real water samples. The average relative recoveries obtained from the
      fortified samples varied between 90 and 108% with the relative standard
      deviations of 5.3-10.7%.

PMID- 29205907
TI  - Prevalence, treatment patterns and control rates of metabolic syndrome in a
      Chinese diabetic population: China Cardiometabolic Registries 3B study.
AB  - AIMS/INTRODUCTION: To investigate the prevalence and risk factors of metabolic
      syndrome (MetS) in Chinese type 2 diabetes mellitus patients, and assess the
      effect of MetS on the treatment patterns and blood glucose, blood pressure and
      blood lipids goal achievements. MATERIALS AND METHODS: Data from 25,454 type 2
      diabetes mellitus patients including demographic data, anthropometric
      measurements, treatment patterns, and blood glucose and lipid profiles were
      retrospectively analyzed. RESULTS: Using modified Adult Treatment Panel III MetS
      criteria, the prevalence of MetS was 57.4% in type 2 diabetes mellitus patients.
      Multivariable logistic regression analysis showed that type 2 diabetes mellitus
      patients, who also fulfilled the criteria for MetS, tended to be women, living in
      the northeast, with a diabetes duration >=5 years and leading a sedentary
      lifestyle. Most MetS (53.4%) and non-MetS (57%) diabetes patients received oral
      hypoglycemic drugs. Insulin or insulin combination therapies were more applied in
      MetS (37.5%) than in non-MetS (33.1%) diabetes patients, and the percentages of
      MetS diabetes patients receiving antihypertensive and lipid-modulating drugs were
      52.9% and 28.2% vs 38.3% and 19.3% of the non-MetS diabetes patients. Just 37.5%,
      15.6% and 32.9% of the MetS diabetes patients vs 54.6%, 45.6% and 40.4% of the
      non-MetS diabetes patients achieved the individual target goals for control of
      blood glucose (glycosylated hemoglobin <7%), blood pressure (systolic blood
      pressure <130 mmHg, diastolic blood pressure <80 mmHg) and blood lipids (total
      cholesterol <4.5 mmol/L), whereas just 2.1% achieved all three target goals.
      CONCLUSIONS: MetS with a high prevalence in Chinese type 2 diabetes mellitus
      patients is associated with poor blood glucose, blood pressure and blood lipids
      control rate.

PMID- 29205909
TI  - Standing Up for Student Health: An Application of the Health Action Process
      Approach for Reducing Student Sedentary Behavior-Randomised Control Pilot Trial.
AB  - BACKGROUND: Sedentary behavior (SB) has been associated with chronic diseases.
      University students are a high-risk population for excessive SB. The purpose of
      this pilot study was to determine if a Health Action Process Approach (HAPA)
      based intervention, specifically action and coping planning, would increase
      student break frequency and decrease duration. METHODS: Fifty-two university
      students (14 men, mean age 23.5) were randomised into an 8-week HAPA-treatment
      (sedentary behavior) or HAPA-control (nutrition) group. Participants completed an
      SB questionnaire that assessed break frequency and duration of student SB
      (Baseline, Weeks 1-6 Treatment, and Weeks 7-8 Follow-up), and received behavioral
      counselling on either dietary information or SB (Baseline and Week 3). RESULTS:
      An intent-to-treat analysis revealed a significant group by time interaction
      effect for student break frequency (p = .05, etarho2 = 0.27), and a non
      significant effect for student break duration (p = .10, etarho2 = 0.23). For
      occupational (student) break frequency and duration, the large accompanying
      effect sizes favored the treatment group. CONCLUSIONS: The current pilot study
      provides preliminary evidence for the potential of a HAPA-based intervention for
      increasing student break frequency in full-time university students.

PMID- 29205910
TI  - Role of intravenous immunoglobulin in the treatment of Kawasaki disease.
AB  - Intravenous immunoglobulin (IVIg) is a purified plasma product that is used for
      many immune-deficient conditions and autoimmune conditions. Use of IVIg for
      treatment for Kawasaki disease (KD) is critical for control of inflammation. The
      American Heart Association (AHA) recommends a single infusion of 2 g/kg
      preferably given during the first 10 days of illness. In this review, we have
      discussed the possible mechanisms of action of IVIg in KD and its clinical usage
      in this condition.

PMID- 29205911
TI  - Approaches to Electrolyte Solvent Selection for Poly-Anthraquinone Sulfide
      Organic Electrode Material.
AB  - Organic materials such as polyanthraquinone sulfide (PAQS) are receiving
      increased attention as electrodes for energy storage systems owing to their good
      environmental compatibility, high rate capability, and large charge-storage
      capacity. However, one of their limitations is the solubility in organic solvents
      typically composing the electrolytes. Here, the solubility of PAQS was tested in
      17 different solvents using UV/Vis spectroscopy. The results show that PAQS
      exhibits a very wide range of solubility according to the nature of the solvent
      and the obtained trend agrees well with the predictions from Hansen solubility
      analysis. Furthermore, the transport properties (conductivity, sigma, and
      viscosity, eta) of selected electrolytes composed of non-solubilising solvents
      with 1 m LiTFSI are compared and discussed in the temperature range from -40 
      degrees C to 80  degrees C. In the second part of this study, the electrochemical
      characterization of PAQS as electrode material in selected pure or mixture of
      solvents with 1 m LiTFSI as salt was made in half-cells by a galvanostatic
      method. In a methylglutaronitrile (2MeGLN)-based electrolyte that exhibits low
      solubility of PAQS, it appears that the capacity fade is intricately linked to
      the large irreversibility of the second step of the redox process. Although the
      standard cyclic carbonate solvents mixture (ethylene carbonate and propylene
      carbonate) led to rapid capacity fade in the initial 10-15 cycles owing to their
      high solubilising ability. Finally, it is shown that a pure linear alkylcarbonate
      (dimethyl carbonate) or binary mixture of ether-based (dioxolane/dimethoxy
      ethane) electrolyte is much more compatible for enhanced capacity retention in
      PAQS with more than 120 mAh g-1 for 1000 cycles at 4 C.

PMID- 29205912
TI  - ADP-ribosylation of DNA moving into focus.
AB  - In this issue of The FEBS Journal, Munnur and Ahel describe the reversible mono
      ADP-ribosylation of DNA by PARP3, a member of the poly-ADP-ribose-polymerase
      family known to modify proteins. They demonstrate a selective ADP-ribosylation of
      the 5'-phosphate group on DNA ends and show that the modification can be reversed
      by several known ADP-ribosylhydrolases including PARG.

PMID- 29205914
TI  - Online tools for enhancing presentation, understanding, and retention of 3D
      structural data.
AB  - Dr Alexander Wlodawer, an Editor for The FEBS Journal, provides an overview of
      three useful resources for structural biologists: Protopedia, Molstack and the
      Integrated Resource for Reproducibility in Macromolecular Crystallography
      (IRRMC).

PMID- 29205915
TI  - Kinematic Modeling of Mechanocatalytic Depolymerization of alpha-Cellulose and
      Beechwood.
AB  - Mechanocatalytic depolymerization of lignocellulose presents a promising method
      for the solid-state transformation of acidified raw biomass into water-soluble
      products (WSPs). However, the mechanisms underlining the utilization of
      mechanical forces in the depolymerization are poorly understood. A kinematic
      model of the milling process is applied to assess the energy dose transferred to
      cellulose during its mechanocatalytic depolymerization under varied conditions
      (rotational speed, milling time, ball size, and substrate loading). The data set
      is compared to the apparent energy dose calculated from the kinematic model and
      reveals key features of the mechanocatalytic process. At low energy doses, a
      rapid rise in the WSP yield associated with the apparent energy dose is observed.
      However, at a higher energy dose obtained by extended milling duration or high
      milling speeds, the formation of a substrate cake layer on the mill vials appear
      to buffer the mechanical forces, preventing full cellulose conversion into WSPs.
      By contrast, for beechwood, there exists a good linear dependence between the WSP
      yield and the energy dose provided to the substrate over the entire range of WSP
      yields. As the formation of a substrate cake in depolymerization of beechwood is
      less severe than that for the cellulose experiments, the current results verify
      the hypothesis regarding the negative effect of a substrate layer formed on the
      mill vials upon the depolymerization process. Overall, the current findings
      provide valuable insight into relationships between the energy dose and the
      extent of cellulose depolymerization effected by the mechanocatalytic process.

PMID- 29205916
TI  - Leptin in Maternal Plasma and Cord Blood as a Predictor of Offspring Adiposity at
      5 Years: A Follow-up Study.
AB  - OBJECTIVE: Perinatal leptin exposure may modulate the risk of adiposity in early
      childhood. In previous analyses, negative associations between maternal (32
      weeks' gestation) and cord blood leptin and offspring body composition at 2 years
      were observed. METHODS: Associations between maternal/cord blood leptin were
      assessed with indirect (i.e., body weight, BMI percentiles, sum of 4 skinfold
      thicknesses), and direct (i.e., ultrasonography, magnetic resonance imaging in a
      subgroup) growth and adipose tissue (AT) measurements in 120 children aged 3 to 5
      years. RESULTS: Maternal leptin was not shown to be associated with offspring
      body composition in univariate analyses. In adjusted analyses, some weak negative
      associations were observed with weight and BMI percentiles but not with sum of 4
      skinfold thicknesses or calculated body fat at 3 to 5 years. Cord blood leptin
      was inversely related to offspring body composition, but effect sizes were small
      and not consistently statistically significant. No evidence of associations with
      direct AT measurements was observed. CONCLUSIONS: Although some negative
      relationships with indirect measurements of AT mass were observed, the results of
      this study do not provide sufficient evidence that maternal plasma or cord blood
      leptin is clinically relevant predictors of obesity or body fat distribution in
      early childhood.

PMID- 29205918
TI  - Acknowledging the peer reviewers of Journal of Medical Radiation Sciences October
      2016-September 2017.

PMID- 29205917
TI  - Targeted in situ metatranscriptomics for selected taxa from mesophilic and
      thermophilic biogas plants.
AB  - Biogas production is performed anaerobically by complex microbial communities
      with key species driving the process. Hence, analyses of their in situ activities
      are crucial to understand the process. In a previous study, metagenome sequencing
      and subsequent genome binning for different production-scale biogas plants (BGPs)
      resulted in four genome bins of special interest, assigned to the phyla
      Thermotogae, Fusobacteria, Spirochaetes and Cloacimonetes, respectively, that
      were genetically analysed. In this study, metatranscriptome sequencing of the
      same BGP samples was conducted, enabling in situ transcriptional activity
      determination of these genome bins. For this, mapping of metatranscriptome reads
      on genome bin sequences was performed providing transcripts per million (TPM)
      values for each gene. This approach revealed an active sugar-based metabolism of
      the Thermotogae and Spirochaetes bins and an active amino acid-based metabolism
      of the Fusobacteria and Cloacimonetes bins. The data also hint at syntrophic
      associations of the four corresponding species with methanogenic Archaea.

PMID- 29205919
TI  - We can and do make a difference by improving medical radiation services in rural
      and remote locations.
AB  - This is an editorial referring to the benefits that medical radiation
      practitioners can provide to the communities they live and work in.

PMID- 29205921
TI  - The dioxygenase GIM2 functions in seed germination by altering gibberellin
      production in Arabidopsis.
AB  - The phytohormones gibberellic acid (GA) and abscisic acid (ABA) antagonistically
      control seed germination. High levels of GA favor seed germination, whereas high
      levels of ABA hinder this process. The direct relationship between GA
      biosynthesis and seed germination ability need further investigation. Here, we
      identified the ABA-insensitive gain-of-function mutant germination insensitive to
      ABA mutant 2 (gim2) by screening a population of XVE T-DNA-tagged mutant lines.
      Based on two loss-of-function gim2-ko mutant lines, the disruption of GIM2
      function caused a delay in seed germination. By contrast, upregulation of GIM2
      accelerated seed germination, as observed in transgenic lines overexpressing GIM2
      (OE). We detected a reduction in endogenous bioactive GA levels and an increase
      in endogenous ABA levels in the gim2-ko mutants compared to wild type.
      Conversely, the OE lines had increased endogenous bioactive GA levels and
      decreased endogenous ABA levels. The expression levels of a set of GA- and/or ABA
      related genes were altered in both the gim2-ko mutants and the OE lines. We
      confirmed that GIM2 has dioxygenase activity using an in vitro enzyme assay,
      observing that GIM2 can oxidize GA12 . Hence, our characterization of GIM2
      demonstrates that it plays a role in seed germination by affecting the GA
      metabolic pathway in Arabidopsis.

PMID- 29205922
TI  - A Lithium-Air Battery Stably Working at High Temperature with High Rate
      Performance.
AB  - Driven by the increasing requirements for energy supply in both modern life and
      the automobile industry, the lithium-air battery serves as a promising candidate
      due to its high energy density. However, organic solvents in electrolytes are
      likely to rapidly vaporize and form flammable gases under increasing
      temperatures. In this case, serious safety problems may occur and cause great
      harm to people. Therefore, a kind of lithium-air that can work stably under high
      temperature is desirable. Herein, through the use of an ionic liquid and aligned
      carbon nanotubes, and a fiber shaped design, a new type of lithium-air battery
      that can effectively work at high temperatures up to 140  degrees C is developed.
      Ionic liquids can offer wide electrochemical windows and low vapor pressures, as
      well as provide high thermal stability for lithium-air batteries. The aligned
      carbon nanotubes have good electric and heat conductivity. Meanwhile, the fiber
      format can offer both flexibility and weavability, and realize rapid heat
      conduction and uniform heat distribution of the battery. In addition, the high
      temperature has also largely improved the specific powers by increasing the ionic
      conductivity and catalytic activity of the cathode. Consequently, the lithium-air
      battery can work stably at 140  degrees C with a high specific current of 10 A g
      1 for 380 cycles, indicating high stability and good rate performance at high
      temperatures. This work may provide an effective paradigm for the development of
      high-performance energy storage devices.

PMID- 29205923
TI  - Home-based interval training increases endurance capacity in adults with complex
      congenital heart disease.
AB  - OBJECTIVE: The beneficial effects of exercise training in acquired heart failure
      and coronary artery disease are well known and have been implemented in current
      treatment guidelines. Knowledge on appropriate exercise training regimes for
      adults with congenital heart disease is limited, thus further studies are needed.
      The aim of this study was to examine the effect of home-based interval exercise
      training on maximal endurance capacity and peak exercise capacity. DESIGN:
      Randomized controlled trial. METHODS: Twenty-six adults with complex congenital
      heart disease were recruited from specialized units for adult congenital heart
      disease. Patients were randomized to either an intervention group-12 weeks of
      home-based interval exercise training on a cycle ergometer (n = 16), or a control
      group (n = 10). The latter was instructed to maintain their habitual physical
      activities. An incremental cardiopulmonary exercise test and a constant work rate
      cardiopulmonary exercise test at 75% of peak workload were performed
      preintervention and postintervention. RESULTS: Twenty-three patients completed
      the protocol and were followed (intervention n = 13, control n = 10).
      Postintervention exercise time at constant work rate cardiopulmonary exercise
      test increased in the intervention group compared to controls (median[range] 12[
      4 to 52]min vs 0[-4 to 5]min, P = .001). At incremental cardiopulmonary exercise
      test, peak VO2 increased 15% within the intervention group (P = .019) compared to
      2% within the control group (P = .8). However, in comparison between the groups
      no difference was found (285[-200 to 535] ml/min vs 17[-380 to 306] ml/min, P =
      .10). In addition, peak workload at incremental cardiopulmonary exercise test
      increased in the intervention group compared to controls (20[-10 to 70]W vs 0[-20
      to 15]W, P = .003). CONCLUSION: Home-based interval exercise training increased
      endurance capacity and peak exercise capacity in adults with complex congenital
      heart disease. Aerobic endurance might be more relevant than peak oxygen uptake
      with regard to daily activities, and therefore a more clinically relevant measure
      to evaluate.

PMID- 29205920
TI  - Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances,
      and Challenges.
AB  - Traditional cell culture and animal models utilized for preclinical drug
      screening have led to high attrition rates of drug candidates in clinical trials
      due to their low predictive power for human response. Alternative models using
      human cells to build in vitro biomimetics of the human body with physiologically
      relevant organ-organ interactions hold great potential to act as "human
      surrogates" and provide more accurate prediction of drug effects in humans. This
      review is a comprehensive investigation into the development of tissue-engineered
      human cell-based microscale multiorgan models, or multiorgan microphysiological
      systems for drug testing. The evolution from traditional models to macro- and
      microscale multiorgan systems is discussed in regards to the rationale for recent
      global efforts in multiorgan microphysiological systems. Current advances in
      integrating cell culture and on-chip analytical technologies, as well as proof-of
      concept applications for these multiorgan microsystems are discussed. Major
      challenges for the field, such as reproducibility and physiological relevance,
      are discussed with comparisons of the strengths and weaknesses of various systems
      to solve these challenges. Conclusions focus on the current development stage of
      multiorgan microphysiological systems and new trends in the field.

PMID- 29205924
TI  - Genomic epidemiology of the emerging pathogen Batrachochytrium dendrobatidis from
      native and invasive amphibian species in Chile.
AB  - Emerging fungal diseases represent a threat to food security, animal and human
      health worldwide. Amphibian chytridiomycosis, caused by the fungus
      Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and
      well-documented amphibian population declines and extinctions. For the first
      time, Bd was cultured from native and non-native wild amphibians in Chile.
      Phylogenomic analyses revealed that Chilean isolates AVS2, AVS4 and AVS7 group
      within the global panzootic lineage of Bd (BdGPL) in a single highly supported
      clade that includes a genotype previously isolated from the United Kingdom. Our
      results extend the known distribution of BdGPL in South America and suggest a
      single and relatively recent introduction of BdGPL into the country, providing
      additional support to the role of anthropogenic activity in the global spread of
      this panzootic lineage.

PMID- 29205925
TI  - Electrocatalytic Alloys for CO2 Reduction.
AB  - Electrochemically reducing CO2 using renewable energy is a contemporary global
      challenge that will only be met with electrocatalysts capable of efficiently
      converting CO2 into fuels and chemicals with high selectivity. Although many
      different metals and morphologies have been tested for CO2 electrocatalysis over
      the last several decades, relatively limited attention has been committed to the
      study of alloys for this application. Alloying is a promising method to tailor
      the geometric and electric environments of active sites. The parameter space for
      discovering new alloys for CO2 electrocatalysis is particularly large because of
      the myriad products that can be formed during CO2 reduction. In this Minireview,
      mixed-metal electrocatalyst compositions that have been evaluated for CO2
      reduction are summarized. A distillation of the structure-property relationships
      gleaned from this survey are intended to help in the construction of guidelines
      for discovering new classes of alloys for the CO2 reduction reaction.

PMID- 29205926
TI  - A retrospective review of the persistence on bDMARDs prescribed for the treatment
      of rheumatoid arthritis in the Australian population.
AB  - AIM: To describe the persistence of biologic disease modifying anti-rheumatic
      drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the
      influence of methotrexate and other conventional DMARD (cDMARD) concomitant
      medications, and treatment line on bDMARD persistence and glucocorticoids usage.
      METHOD: RA patients, from the 10% Australian Medicare random sample, aged >=18
      for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti
      tumor necrosis factor-alpha (anti-TNFalpha) agents were combined as they were
      equivalent. RESULTS: Data from 1230 patients were analyzed. For all patients the
      12-month persistence rates (based on Kaplan-Meier estimates) were 76% for
      intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV
      infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and
      abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for
      tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the
      second-line setting. Median treatment persistence was 40 months tocilizumab (95%
      CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl:
      18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed
      for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For
      tocilizumab, persistence was robust with or without concomitant medications. The
      median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0
      mg/day (min 0, max 17.3) over 2 years. CONCLUSIONS: Treatment persistence was
      longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was
      influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This
      real-world data highlights that persistence on bDMARDs differs according to
      biologics mode of action and co-therapy.

PMID- 29205927
TI  - Areolar lymphocytoma in a child: A rare cutaneous presentation of borreliosis.
AB  - Lyme disease is a common tick-borne infection caused by Borrelia burgdorferi in
      the United States, where infection is most prevalent in the northeastern and mid
      Atlantic states. Although classically associated with erythema migrans, Lyme
      disease caused by Borrelia species found in Europe may also present with other
      cutaneous findings. Here we report the case of a girl who was clinically
      diagnosed with Lyme disease based on her history of recent travel and the
      appearance of an areolar lymphocytoma; this was confirmed by testing. Testing for
      European Lyme disease does not follow the testing algorithm that the Centers for
      Disease Control and Prevention recommends and may be easily missed. Our case
      serves as an important reminder that common infections can have varying
      presentations depending on their region of acquisition and may require
      specialized testing for accurate diagnosis.

PMID- 29205928
TI  - Recent Progress in Micro/Nanoreactors toward the Creation of Artificial
      Organelles.
AB  - Artificial organelles created from a bottom up approach are a new type of
      engineered materials, which are not designed to be living but, instead, to mimic
      some specific functions inside cells. By doing so, artificial organelles are
      expected to become a powerful tool in biomedicine. They can act as nanoreactors
      to convert a prodrug into a drug inside the cells or as carriers encapsulating
      therapeutic enzymes to replace malfunctioning organelles in pathological
      conditions. For the design of artificial organelles, several requirements need to
      be fulfilled: a compartmentalized structure that can encapsulate the synthetic
      machinery to perform an enzymatic function, as well as a means to allow for
      communication between the interior of the artificial organelle and the external
      environment, so that substrates and products can diffuse in and out the carrier
      allowing for continuous enzymatic reactions. The most recent and exciting
      advances in architectures that fulfill the aforementioned requirements are
      featured in this review. Artificial organelles are classified depending on their
      constituting materials, being lipid and polymer-based systems the most prominent
      ones. Finally, special emphasis will be put on the intracellular response of
      these newly emerging systems.

PMID- 29205930
TI  - Post-diagnosis weight loss as a prognostic factor in non-small cell lung cancer.
AB  - BACKGROUND: Cachexia and its most visible manifestation, weight loss, represent
      important poor prognostic factors for patients with non-small cell lung cancer.
      This work examines how severity of weight loss as an indicator of cachexia
      affects outcomes. METHODS: In a retrospective observational study of electronic
      medical records, patients with non-small cell lung cancer were monitored for
      weight loss from an initial assessment (within 2 months of index diagnosis) to a
      landmark at 5 months (at least 3 months after initial assessment). Patients who
      survived to the landmark were then followed to determine the association of
      baseline body mass index (BMI) and weight loss during the assessment period with
      outcomes. Patients were clustered to determine how BMI and weight loss related to
      survival as approximated by time of last appearance in the database, a strong
      proxy for time of death. RESULTS: Twelve thousand one hundred and one patients
      were divided into 5 cachexia risk groups based on a combination of weight loss
      and initial BMI. More severe groups demonstrated progressively worse outcomes,
      with the most severe group surviving for a median of 263 days (95% CI 254-274)
      from index and having a 1-year survival rate of 31%. The least severe group
      survived for a median of 825 days from index (95% CI 768-908) and had a 1-year
      survival rate of 78%. Cachexia risk group was a stronger predictor of survival
      than any baseline variable, including disease stage, performance status, or age.
      CONCLUSIONS: In this study, we showed that increasing weight loss and, to a
      lesser extent, decreasing BMI, led to substantially worse outcomes for non-small
      cell lung cancer patients independent of other variables. We suggest risk score
      groups that provide an improved approach for identifying poor prognosis patients
      with the greatest need.

PMID- 29205929
TI  - Dendritic cell targeted HIV-1 gag protein vaccine provides help to a recombinant
      Newcastle disease virus vectored vaccine including mobilization of protective
      CD8+ T cells.
AB  - INTRODUCTION: Recombinant Newcastle Disease virus (rNDV) vectored vaccines are
      safe mucosal applicable vaccines with intrinsic immune-modulatory properties for
      the induction of efficient immunity. Like all viral vectored vaccines repeated
      inoculation via mucosal routes invariably results to immunity against viral
      vaccine vectors. To obviate immunity against viral vaccine vectors and improve
      the ability of rNDV vectored vaccines in inducing T cell immunity in murine air
      way we have directed dendritic cell targeted HIV-1 gag protein (DEC-Gag) vaccine;
      for the induction of helper CD4+ T cells to a Recombinant Newcastle disease virus
      expressing codon optimized HIV-1 Gag P55 (rNDV-L-Gag) vaccine. METHODS: We do so
      through successive administration of anti-DEC205-gagP24 protein plus polyICLC
      (DEC-Gag) vaccine and rNDV-L-Gag. First strong gag specific helper CD4+ T cells
      are induced in mice by selected targeting of anti-DEC205-gagP24 protein vaccine
      to dendritic cells (DC) in situ together with polyICLC as adjuvant. This
      targeting helped T cell immunity develop to a subsequent rNDV-L-Gag vaccine and
      improved both systemic and mucosal gag specific immunity. RESULTS: This
      sequential DEC-Gag vaccine prime followed by an rNDV-L-gag boost results to
      improved viral vectored immunization in murine airway, including mobilization of
      protective CD8+ T cells to a pathogenic virus infection site. CONCLUSION: Thus,
      complementary prime boost vaccination, in which prime and boost favor distinct
      types of T cell immunity, improves viral vectored immunization, including
      mobilization of protective CD8+ T cells to a pathogenic virus infection site such
      as the murine airway.

PMID- 29205931
TI  - Photoporation Using Carbon Nanotubes for Intracellular Delivery of Molecules and
      Its Relationship to Photoacoustic Pressure.
AB  - Exposure of carbon-black (CB) nanoparticles to near-infrared nanosecond-pulsed
      laser energy can cause efficient intracellular delivery of molecules by
      photoporation. Here, cellular bioeffects of multi-walled carbon nanotubes
      (MWCNTs) and single-walled carbon nanotubes (SWCNTs) are compared to those of CB
      nanoparticles. In DU145 prostate-cancer cells, photoporation using CB
      nanoparticles transitions from (i) cells with molecular uptake to (ii) nonviable
      cells to (iii) fragmented cells with increasing laser fluence, as seen
      previously. In contrast, photoporation with MWCNTs causes uptake and, at higher
      fluence, fragmentation, but does not generate nonviable cells, and SWCNTs show
      little evidence of bioeffects, except at extreme laser conditions, which generate
      nonviable cells and fragmentation, but no significant uptake. These different
      behaviors cannot be explained by photoacoustic pressure output from the
      particles. All particle types emit a single, ~100 ns, mostly positive-pressure
      pulse that increases in amplitude with laser fluence. Different particle types
      emit different peak pressures, which are highest for SWCNTs, followed by CB
      nanoparticles and then MWCNTs, which does not correlate with cellular bioeffects
      between different particle types. This study concludes that cellular bioeffects
      depend strongly on the type of carbon nanoparticle used during photoporation and
      that photoacoustic pressure is unlikely to play a direct mechanistic role in the
      observed bioeffects.

PMID- 29205932
TI  - Designing synbiotics for improved human health.

PMID- 29205933
TI  - A Highly Selective 3D Spiked Ultraflexible Neural (SUN) Interface for Decoding
      Peripheral Nerve Sensory Information.
AB  - Artificial sensors on the skin are proposed as a way to capture information that
      can be used in intracortical microstimulation or peripheral intraneural
      stimulation to restore sensory feedback to persons with tetraplegia. However, the
      ability of these artificial sensors to replicate the density and complexity of
      the natural mechanoreceptors is limited. One relatively unexplored approach is to
      make use of the signals from surviving tactile and proprioceptive receptors in
      existing limbs by recording from their transmitting axons within the primary
      sensory nerves. Here, a novel spiked ultraflexible neural (SUN) interface that is
      implanted into the peripheral nervous system to capture sensory information from
      these mechanoreceptors in acute rat experiments is described. The novel 3D
      design, which integrates spiked structures for intrafascicular nerve recording
      with an ultraflexible substrate, enables a unique conformal interface to the
      target nerve. With the high-quality recording (average signal-to-noise-ratio of
      1.4) provided by the electrode, tactile from proprioceptive stimuli can be
      differentiated in terms of the firing rate. In toe pinching experiments, high
      spatial resolution classification can be achieved with support vector machine
      classifier. Further work remains to be done to assess the chronic recording
      capability of the SUN interface.

PMID- 29205934
TI  - Advances in Nanoporous Anodic Alumina-Based Biosensors to Detect Biomarkers of
      Clinical Significance: A Review.
AB  - There is a strong and growing demand for compact, portable, rapid, and low-cost
      devices to detect biomarkers of interest in clinical and point-of-care
      diagnostics. Such devices aid in early diagnosis of diseases without the need to
      rely on expensive and time-consuming large instruments in dedicated laboratories.
      Over the last decade, numerous biosensors have been developed for detection of a
      wide range of clinical biomarkers including proteins, nucleic acids, growth
      factors, and bacterial enzymes. Various transduction techniques have been
      reported based on biosensor technology that deliver substantial advances in
      analytical performance, including sensitivity, reproducibility, selectivity, and
      speed for monitoring a wide range of human health conditions. Nanoporous anodic
      alumina (NAA) has been used extensively for biosensing applications due to its
      inherent optical and electrochemical properties, ease of fabrication, large
      surface area, tunable properties, and high stability in aqueous environment. This
      review focuses on NAA-based biosensing systems for detection of clinically
      significant biomarkers using various detection techniques with the main focus
      being on electrochemical and optical transduction methods. The review covers an
      overview of the importance of biosensors for biomarkers detection, general
      (surface and structural) properties and fabrication of NAA, and NAA-based
      biomarker sensing systems.

PMID- 29205935
TI  - Self-Template Synthesis of Hybrid Porous Co3 O4 -CeO2 Hollow Polyhedrons for High
      Performance Supercapacitors.
AB  - In this work, hybrid porous Co3 O4 -CeO2 hollow polyhedrons have been
      successfully obtained via a simple cation-exchange route followed by heat
      treatment. In the synthesis process, ZIF-67 polyhedron frameworks are firstly
      prepared, which not only serve as a host for the exchanged Ce3+ ions but also act
      as the template for the synthesis of hybrid porous Co3 O4 -CeO2 hollow
      polyhedrons. When utilized as electrode materials for supercapacitors, the hybrid
      porous Co3 O4 -CeO2 hollow polyhedrons delivered a large specific capacitance of
      1288.3 F g-1 at 2.5 A g-1 and a remarkable long lifespan cycling stability (<3.3
      % loss after 6000 cycles). Furthermore, an asymmetric supercapacitor (ASC) device
      based on hybrid porous Co3 O4 -CeO2 hollow polyhedrons was assembled. The ASC
      device possesses an energy density of 54.9 W h kg-1 , which can be retained to
      44.2 W h kg-1 even at a power density of 5100 W kg-1 , indicating its promising
      application in electrochemical energy storage. More importantly, we believe that
      the present route is a simple and versatile strategy for the preparation of other
      hybrid metal oxides with desired structures, chemical compositions and
      applications.

PMID- 29205936
TI  - Facile methods for heterologous production of bacterial microcompartments in
      diverse host species.

PMID- 29205937
TI  - Experience with an abdominal compression band for radiotherapy of upper abdominal
      tumours.
AB  - INTRODUCTION: Radiotherapy outcomes are influenced by treatment delivery
      geometric accuracy and organ-at-risk dose. The location of abdominal structures
      such as the liver, kidneys and tumour volumes can be strongly influenced by
      respiratory motion. This increases geometric uncertainty and dose to organs-at
      risk. One common method of minimising respiratory motion is abdominal compression
      (AC). METHODS: Fifteen patients being treated for radiotherapy to upper abdominal
      tumours were analysed. Each patient underwent 2 four-dimensional computerised
      tomography (4D-CT) scans, one with and one without AC with a pneumatic
      compression belt. Liver and kidney positions were measured on the 4DCT scans at
      the peak inspiratory and expiratory respiratory phases. The patient received
      radiation therapy treatment planned on the CT data set with the technique
      (compression or no compression) that provided the least respiratory motion.
      RESULTS: There was no statistically significant motion difference over the sample
      population with AC for the kidneys or liver. Of the 14 evaluable patients, 4, 6
      and 6 saw reduction in superior-inferior motion for left kidney, right kidney and
      liver respectively. The remainder either had negligible (<2 mm) or increase in
      motion with AC. For anterior-posterior motion, 2, 2 and 1 saw a reduction for
      left-kidney, right-kidney and liver respectively. CONCLUSION: AC through the use
      of a pneumatic compression belt was found to result in inconsistent reduction in
      kidney and liver respiratory motion. It is recommended that the effect of AC is
      evaluated on a per-patient basis.

PMID- 29205938
TI  - Peptide-Functionalized Polyurethane Coatings Prepared via Grafting-To Strategy to
      Selectively Promote Endothelialization.
AB  - Endothelialization, formation of endothelial cells (ECs) layer on cardiovascular
      implant surface, is considered an ideal approach to prevent restenosis
      (renarrowing of blood vessel mainly due to the accumulation of proliferated
      vascular smooth muscle cells, SMCs) and thrombosis. In this study, the
      possibility of using polyurethane (PU) as a coating platform for
      functionalization with peptide to enhance endothelialization on implants is
      explored. PUs are synthesized through metal-free organocatalytic polymerization
      followed by chemical conjugation with an EC-specific REDV peptide through thiol
      ene reaction. Meanwhile, the free isocyanate groups of PU allow for covalent
      grafting of REDV-functionalized PU (PU/REDV) to silanize implant materials
      (nitinol and PET). PU/REDV coating with peptide grafting density of ~2 nmol cm-2
      selectively accommodates primary human umbilical vein ECs (HUVECs) and retards
      spreading of primary human umbilical artery SMCs (HUASMCs). In addition, a layer
      of HUVECs is formed within 3 d on PU/REDV-coated surfaces, while proliferation of
      HUASMCs is inhibited. The selectivity is further confirmed by coculture of HUVECs
      and HUASMCs. Moreover, the PU/REDV-coated surfaces are less thrombogenic as
      evidenced by reduced number and activity of adhered platelets. Therefore, PU/REDV
      can be potentially used as a coating of cardiovascular implants to prevent
      restenosis and thrombosis by promoting endothelialization.

PMID- 29205939
TI  - Recent advances in pediatric rheumatology: April to June 2017.

PMID- 29205940
TI  - Relation of Serum ADMA, Apelin-13 and LOX-1 Levels with Inflammatory and
      Echocardiographic Parameters in Hemodialysis Patients.
AB  - Cardiovascular diseases are the leading causes of mortality in patients with
      chronic kidney disease. Nitric oxide has a critical role in both endothelial
      dysfunction and the atherosclerosis process. We aimed to investigate the
      relationships between serum asymmetric dimethyl arginine (ADMA), LOX-1, and
      Apelin-13 levels, which are known to act over nitric oxide with endothelial
      dysfunction and cardiac morphology as well as with each other in hemodialysis
      patients. The study comprised a total of 120 patients (53 females and 67 males)
      receiving hemodialysis three times a week for at least 6 months and an age-gender
      matched control group (55 females and 58 males). Serum ADMA, LOX-1, and Apelin-13
      levels were measured using the ELISA technique. Echocardiography, 24-h blood
      pressure monitoring by the Holter and carotid artery intima-media thickness
      (CIMT) measurement was performed on all of the included subjects. The
      associations between serum ADMA, LOX-1, and Apelin-13 levels with CIMT,
      echocardiographic parameters [left ventricular mass (LVM) and left ventricular
      mass index (LVMI)], and inflammatory markers [high sensitive C-reactive protein
      (hsCRP) and neutrophil lymphocyte ratio (NLR)] were evaluated by correlation
      analysis. Serum ADMA, Apelin-13, and LOX-1 levels were significantly higher in
      the hemodialysis group than the controls (P < 0.001, P < 0.001, and P < 0.001,
      respectively). CIMT, hsCRP, and NLR levels were also significantly higher in the
      hemodialysis group (P < 0.05, P < 0.001, P < 0.001, respectively). Significant
      correlations were observed among the serum ADMA, Apelin-13, and LOX-1 levels.
      Moreover, notably positive correlations were found between these three
      biochemical markers and LVM, LVMI, hsCRP, and CIMT. Serum ADMA, Apelin-13, and
      LOX-1 levels can be indicators not only for the inflammatory process but also for
      the pathogenesis of cardiovascular diseases in hemodialysis patients.

PMID- 29205941
TI  - Application of aqueous two-phase micellar system to improve extraction of
      adenoviral particles from cell lysate.
AB  - Viral vectors are important in medical approaches, such as disease prevention and
      gene therapy, and their production depends on efficient prepurification steps. In
      the present study, an aqueous two-phase micellar system (ATPMS) was evaluated to
      extract human adenovirus type 5 particles from a cell lysate. Adenovirus was
      cultured in human embryonic kidney 293 (HEK-293) cells to a concentration of 1.4
      * 1010 particles/mL. Cells were lysed, and the system formed by direct addition
      of Triton X-114 in a 23 full factorial design with center points. The systems
      were formed with Triton X-114 at a final concentration of 1.0, 6.0, and 11.0%
      (w/w), cell lysate pH of 6.0, 6.5, and 7.0, and incubation temperatures at 33,
      35, and 37  degrees C. Adenovirus particles recovered from partition phases were
      measured by qPCR. The best system condition was with 11.0% (w/w) of Triton X-114,
      a cell lysate pH of 7.0, and an incubation temperature at 33  degrees C, yielding
      3.51 * 1010 adenovirus particles/mL, which increased the initial adenovirus
      particles concentration by 2.3-fold, purifying it by 2.2-fold from the cell
      lysate, and removing cell debris. In conclusion, these results demonstrated that
      the use of an aqueous two-phase micellar system in the early steps of downstream
      processing could improve viral particle extraction from cultured cells while
      integrating clarification, concentration, and prepurification steps.

PMID- 29205943
TI  - Self-Complementary Dimers of Oxalamide-Functionalized Resorcinarene
      Tetrabenzoxazines.
AB  - Self-complementarity is a useful concept in supramolecular chemistry, molecular
      biology and polymeric systems. Two resorcinarene tetrabenzoxazines decorated with
      four oxalamide groups were synthesized and characterized. The oxalamide groups
      possessed self-complementary hydrogen bonding sites between the carbonyls and
      amide groups. The self-complementary nature of the oxalamide groups resulted in
      self-included dimeric assemblies. The hydrogen bonding interactions within the
      tetrabenzoxazines gave rise to the formation of dimers, which were confirmed by
      single-crystal X-ray diffractions analysis and supported by NMR spectroscopy and
      mass spectrometry. The self-included dimers were connected by numerous and strong
      intermolecular N-H???O and C-H???O hydrogen bonds supplemented with C-H???pi
      interactions, forming one-dimensional polymers, which were then further linked
      into three-dimensional networks.

PMID- 29205944
TI  - Iron Oxide Nanoparticles: Innovative Tool in Cancer Diagnosis and Therapy.
AB  - Although cancer is one of the most dangerous and the second most lethal disease
      in the world, current therapy including surgery, chemotherapy, radiotherapy,
      etc., is highly insufficient not in the view of therapy success rate or the
      amount of side effects. Accordingly, procedures with better outcomes are highly
      desirable. Iron oxide nanoparticles (IONPs) present an innovative tool-ideal for
      innovation and implementation into practice. This review is focused on
      summarizing some well-known facts about pharmacokinetics, toxicity, and the types
      of IONPs, and furthermore, provides a survey of their use in cancer diagnosis and
      therapy.

PMID- 29205942
TI  - Biomaterials-Based Approaches to Tumor Spheroid and Organoid Modeling.
AB  - Evolving understanding of structural and biological complexity of tumors has
      stimulated development of physiologically relevant tumor models for cancer
      research and drug discovery. A major motivation for developing new tumor models
      is to recreate the 3D environment of tumors and context-mediated functional
      regulation of cancer cells. Such models overcome many limitations of standard
      monolayer cancer cell cultures. Under defined culture conditions, cancer cells
      self-assemble into 3D constructs known as spheroids. Additionally, cancer cells
      may recapitulate steps in embryonic development to self-organize into 3D cultures
      known as organoids. Importantly, spheroids and organoids reproduce morphology and
      biologic properties of tumors, providing valuable new tools for research, drug
      discovery, and precision medicine in cancer. This Progress Report discusses uses
      of both natural and synthetic biomaterials to culture cancer cells as spheroids
      or organoids, specifically highlighting studies that demonstrate how these models
      recapitulate key properties of native tumors. The report concludes with the
      perspectives on the utility of these models and areas of need for future
      developments to more closely mimic pathologic events in tumors.

PMID- 29205945
TI  - Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA.
AB  - Herein we report the first exploration of a dual-targeting drug design strategy
      to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of
      indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen
      mustards that respectively target IDO1 and DNA were rationally designed. As the
      first-in-class examples of such molecules, they were found to exhibit
      significantly enhanced anticancer activity in vitro and in vivo with low
      toxicity. This proof-of-concept study has established a critical step toward the
      development of a novel and effective immunotherapy for the treatment of cancers.

PMID- 29205946
TI  - Surveillance of drug abuse in Hong Kong by hair analysis using LC-MS/MS.
AB  - The aim of this study is to reveal the habits of drug abusers in hair samples
      from drug rehabilitation units in Hong Kong. With the application of liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) technology, a total of 1771
      hair samples were analyzed during the period of hair testing service (January
      2012 to March 2016) provided to 14 drug rehabilitation units including non
      governmental organizations (NGOs), rehabilitation centers, and medical clinics.
      Hair samples were analyzed for abused drugs and their metabolites simultaneously,
      including ketamine, norketamine, cocaine, benzoylecgonine, cocaethylene,
      norcocaine, codeine, MDMA, MDA, MDEA, amphetamine, methamphetamine, morphine, 6
      acetylmorphine, phencyclidine, and methadone. The results showed that ketamine
      (77.2%), cocaine (21.3%), and methamphetamine (16.5%) were the frequently
      detected drugs among those drug abusers, which is consistent with the reported
      data. In addition, the usage of multiple drugs was also observed in the hair
      samples. About 29% of drug-positive samples were detected with multiple drug use.
      Our studies prove that our locally developed hair drug-testing method and service
      can be a valid tool to monitor the use of abused drugs, and which could
      facilitate rehabilitation program management.

PMID- 29205947
TI  - Online instructional anatomy videos: Student usage, self-efficacy, and
      performance in upper limb regional anatomy assessment.
AB  - Allied health professionals concur that a sound knowledge of practical gross
      anatomy is vital for the clinician, however, human anatomy courses in allied
      health programs have been identified as high-risk for attrition and failure.
      While anatomists and clinicians agree that learning anatomy via human cadaveric
      instruction is the preferred method, students vary in their reaction to the
      cadaveric learning experience and have differing levels of anatomy self-efficacy.
      This study investigated whether student self-efficacy had an effect on student
      usage of supplemental instructional videos and whether the use of videos had an
      impact on student self-efficacy and/or learning. Anatomy self-efficacy differed
      based on gender and prior performance. Student usage of the videos varied widely
      and students with lower self-efficacy were more inclined to use the resources.
      The provision of the videos did not improve overall cohort performance as
      compared to a historical cohort, however, those students that accessed all video
      sets experienced a greater normalized learning gain compared to students that
      used none or one of the four sets of videos. Student reports and usage patterns
      indicate that the videos were primarily used for practical class preparation and
      revision. Potentially, the videos represent a passive mode of teaching whereas
      active learning has been demonstrated to result in greater learning gains.
      Adapting the videos into interactive tutorials which will provide opportunity for
      feedback and the development of students' self-evaluation may be more
      appropriate. Anat Sci Educ 11: 461-470. (c) 2017 American Association of
      Anatomists.

PMID- 29205948
TI  - VS4 Nanoparticles Anchored on Graphene Sheets as a High-Rate and Stable Electrode
      Material for Sodium Ion Batteries.
AB  - The size and conductivity of the electrode materials play a significant role in
      the kinetics of sodium-ion batteries. Various characterizations reveal that size
      controllable VS4 nanoparticles can be successfully anchored on the surface of
      graphene sheets (GSs) by a simple cationic-surfactant-assisted hydrothermal
      method. When used as an electrode material for sodium-ion batteries, these VS4
      @GS nanocomposites show large specific capacity (349.1 mAh g-1 after 100 cycles),
      excellent long-term stability (84 % capacity retention after 1200 cycles), and
      high rate capability (188.1 mAh g-1 at 4000 mA g-1 ). A large proportion of the
      capacity was contributed by capacitive processes. This remarkable electrochemical
      performance was attributed to synergistic interactions between nanosized VS4
      particles and a highly conductive graphene network, which provided short
      diffusion pathways for Na+ ions and large contact areas between the electrolyte
      and electrode, resulting in considerably improved electrochemical kinetic
      properties.

PMID- 29205949
TI  - Improving Defect-Based Quantum Emitters in Silicon Carbide via Inorganic
      Passivation.
AB  - Defect-based color centers in wide-bandgap crystalline solids are actively being
      explored for quantum information science, sensing, and imaging. Unfortunately,
      the luminescent properties of these emitters are frequently degraded by blinking
      and photobleaching that arise from poorly passivated host crystal surfaces. Here,
      a new method for stabilizing the photoluminescence and charge state of color
      centers based on epitaxial growth of an inorganic passivation layer is presented.
      Specifically, carbon antisite-vacancy pairs (CAV centers) in 4H-SiC, which serve
      as single-photon emitters at visible wavelengths, are used as a model system to
      demonstrate the power of this inorganic passivation scheme. Analysis of CAV
      centers with scanning confocal microscopy indicates a dramatic improvement in
      photostability and an enhancement in emission after growth of an epitaxial AlN
      passivation layer. Permanent, spatially selective control of the defect charge
      state can also be achieved by exploiting the mismatch in spontaneous polarization
      at the AlN/SiC interface. These results demonstrate that epitaxial inorganic
      passivation of defect-based quantum emitters provides a new method for enhancing
      photostability, emission, and charge state stability of these color centers.

PMID- 29205950
TI  - Biodegradable Nanoparticles Enhanced Adhesiveness of Mussel-Like Hydrogels at
      Tissue Interface.
AB  - Popular bioadhesives, such as fibrin, cyanoacrylate, and albumin-glutaraldehyde
      based materials, have been applied for clinical applications in wound healing,
      drug delivery, and bone and soft tissue engineering; however, their performances
      are limited by weak adhesion strength and rapid degradation. In this study a
      mussel-inspired, nanocomposite-based, biodegradable tissue adhesive is developed
      by blending poly(lactic-co-glycolic acid) (PLGA) or N-hydroxysuccinimide modified
      PLGA nanoparticles (PLGA-NHS) with mussel-inspired alginate-dopamine polymer (Alg
      Dopa). Adhesive strength measurement of the nanocomposites on porcine skin-muscle
      constructs reveals that the incorporation of nanoparticles in Alg-Dopa
      significantly enhances the tissue adhesive strength compared to the mussel
      inspired adhesive alone. The nanocomposite formed by PLGA-NHS nanoparticles shows
      higher lap shear strength of 33 +/- 3 kPa, compared to that of Alg-Dopa hydrogel
      alone (14 +/- 2 kPa). In addition, these nanocomposites are degradable and
      cytocompatible in vitro, and elicit in vivo minimal inflammatory responses in a
      rat model, suggesting clinical potential of these nanocomposites as bioadhesives.

PMID- 29205952
TI  - Issue Information - IFA.

PMID- 29205951
TI  - Identification of differentially expressed genes involved in spore germination of
      Penicillium expansum by comparative transcriptome and proteome approaches.
AB  - In this study, Penicillium expansum, a common destructive phytopathogen and
      patulin producer was isolated from naturally infected apple fruits and identified
      by morphological observation and rDNA-internal transcribed spacer analysis.
      Subsequently, a global view of the transcriptome and proteome alteration of P.
      expansum spores during germination was evaluated by RNA-seq (RNA sequencing) and
      iTRAQ (isobaric tags for relative and absolute quantitation) approaches. A total
      of 3,026 differentially expressed genes (DEGs), 77 differentially expressed
      predicted transcription factors and 489 differentially expressed proteins (DEPs)
      were identified. The next step involved screening out 130 overlapped candidates
      through correlation analysis between the RNA-seq and iTRAQ datasets. Part of them
      showed a different expression trend in the mRNA and protein levels, and most of
      them were involved in metabolism and genetic information processing. These
      results not only highlighted a set of genes and proteins that were important in
      deciphering the molecular processes of P. expansum germination but also laid the
      foundation to develop effective control methods and adequate environmental
      conditions.

PMID- 29205953
TI  - Designing the Macrocyclic Dimension in Main Group Chemistry.
AB  - Outside the confines and well-established domain of organic chemistry, the
      systematic building of large macromolecular arrangements based on non-carbon
      elements represents a significant and exciting challenge. Our aim in the past two
      decades has been to develop robust synthetic methods to construct new types of
      main group architectures in a methodical way, principles of design that parallel
      those used in the organic arena. This Concept article addresses the fundamental
      thermodynamic and kinetic problems involved in the design and synthesis of main
      group macrocycles and looks to future developments of macromolecules in this
      area, as well as new applications in coordination chemistry.

PMID- 29205954
TI  - Mechanisms underpinning sympathetic nervous activity and its modulation using
      transcutaneous vagus nerve stimulation.
AB  - NEW FINDINGS: What is the topic of this review? This review briefly considers
      what modulates sympathetic nerve activity and how it may change as we age or in
      pathological conditions. It then focuses on transcutaneous vagus nerve
      stimulation, a method of neuromodulation in autonomic cardiovascular control.
      What advances does it highlight? The review considers the pathways involved in
      eliciting the changes in autonomic balance seen with transcutaneous vagus nerve
      stimulation in relationship to other neuromodulatory techniques. The autonomic
      nervous system, consisting of the sympathetic and parasympathetic branches, is a
      major contributor to the maintenance of cardiovascular variables within
      homeostatic limits. As we age or in certain pathological conditions, the balance
      between the two branches changes such that sympathetic activity is more dominant,
      and this change in dominance is negatively correlated with prognosis in
      conditions such as heart failure. We have shown that non-invasive stimulation of
      the tragus of the ear increases parasympathetic activity and reduces sympathetic
      activity and that the extent of this effect is correlated with the baseline
      cardiovascular parameters of different subjects. The effects could be
      attributable to activation of the afferent branch of the vagus and, potentially,
      other sensory nerves in that region. This indicates that tragus stimulation may
      be a viable treatment in disorders where autonomic activity to the heart is
      compromised.

PMID- 29205955
TI  - Selection of antioxidants against ovarian oxidative stress in mouse model.
AB  - Oxidative stress (OS) plays an important role in the process of ovarian granulosa
      cell apoptosis and follicular atresia. The aim of this study was to select
      antioxidant against OS in ovary tissue. Firstly, we chose the six antioxidants
      and analyzed the reactive oxygen species (ROS) level in the ovary tissue. The
      results showed that proanthocyanidins, gallic acid, curcumin, and carotene
      decrease the ROS level compared with control group. We further demonstrated that
      both proanthocyanidins and gallic acid increase the antioxidant enzymes activity.
      Moreover, change in the ROS level was not observed in proanthocyanidins and
      gallic acid group of brain, liver, spleen, and kidney tissues. Finally, we found
      that proanthocyanidins and gallic acid inhibit pro-apoptotic genes expression in
      granulosa cells. Taken together, proanthocyanidins and gallic acid may be the
      most acceptable and optimal antioxidants specifically against ovarian OS and also
      may be involved in the inhibition of granulosa cells apoptosis in mouse ovary.

PMID- 29205956
TI  - Generating Hydrated Electrons for Chemical Syntheses by Using a Green Light
      Emitting Diode (LED).
AB  - We present the first working system for accessing and utilizing laboratory-scale
      concentrations of hydrated electrons by photoredox catalysis with a green light
      emitting diode (LED). Decisive are micellar compartmentalization and photon
      pooling in an intermediate that decays with second-order kinetics. The only
      consumable is the nontoxic and bioavailable vitamin C. A turnover number of 1380
      shows the LED method to be on par with electron generation by high-power pulsed
      lasers, but at a fraction of the cost. The extreme reducing power of the electron
      and its long unquenched life as a ground-state species are synergistic. We
      demonstrate the applicability to the dechlorination, defluorination, and
      hydrogenation of compounds that are inert towards all other visible-light
      photoredox catalysts known to date. A comprehensive mechanistic investigation
      from microseconds to hours yields results of general validity for photoredox
      catalysis with photon pooling, allowing optimization and upscaling.

PMID- 29205957
TI  - Comparison of two tools to assess dyad feeding interaction in infants with
      gastroesophageal reflux disease.
AB  - PURPOSE: The aim of this study was to compare the Mother-Infant/Toddler Feeding
      Scale (MITFS) and the Nursing Child Assessment Feeding Scale (NCAFS). Specific
      questions were as follows: (1) Are there differences between the results of the
      MITFS and the NCAFS tools in terms of rating infant feeding interactions? And (2)
      does one tool provide a more detailed, nuanced overview of the quality of feeding
      interactions than the other? DESIGN AND METHODS: This comparative descriptive
      study is a secondary analysis of a study evaluating a massage intervention for
      infants with symptoms of gastroesophageal reflux disease (GERD). A feeding
      observation for each dyad was scored using both the NCAFS and MITFS. Infants were
      6-18 weeks of age. RESULTS: There were moderate correlations (r = 0.3-0.8)
      between 11 of 20 possible NCAFS and MITFS mother-related subscales, and between 3
      of 10 possible NCAFS and the MITFS infant-related subscales. A total of 19 dyads
      (83%) had one or more NCAFS subscale scores that were at least 1 standard
      deviation (SD) below normative scores, and 21 dyads (91%) had one or more MITFS
      subscale T-scores that deviated 1 SD from the normative T-scores. Agreement
      between the two instruments on scores deviating from the norm was 78%. PRACTICE
      IMPLICATIONS: Both instruments discussed in this paper are standardized ways of
      assessing an infant feeding. Use of a standardized feeding tool is an objective
      way to evaluate feedings and can potentially identify specific areas of concern
      to guide an individualized intervention for a mother-infant dyad. Thus, nurses
      and other health professionals working with mothers and babies, whether in the
      hospital, pediatrician offices, or clinics would benefit from learning how to use
      a standardized feeding tool. Use of a feeding tool also provides the opportunity
      for nurses to understand the basis of important qualities of a feeding
      interaction, and a way for nurses who regularly feed infants to self-evaluate
      their feeding methods. This may minimize less than optimal interactions and allow
      for optimal support for infants during feedings by mothers and nurses.

PMID- 29205958
TI  - Encapsulation of Gold Nanoparticles into DNA Minimal Cages for 3D-Anisotropic
      Functionalization and Assembly.
AB  - Gold nanoparticles (AuNPs) endowed with anisotropic DNA valency are an important
      class of materials, as they can assemble into complex structures with a minimal
      number of DNA strands. However, methods to encode 3D DNA strand patterns on AuNPs
      with a controlled number of unique DNA strands in a predesigned spatial
      arrangement remain elusive. In this work, a simple one-step method to yield such
      DNA-decorated AuNPs is demonstrated, through encapsulating AuNPs into DNA minimal
      nanocages. The AuNP@DNA cage encapsulation complex inherits the 3D anisotropic
      molecular information from the DNA nanocage with enhanced structural stability.
      The DNA nanocage can be further functionalized and used as a building block for
      the self-assembly of complex architectures, such as dimers and trimers,
      programmed assemblies with sequential growth DNA backbones and DNA origami.

PMID- 29205960
TI  - What do medical students learn from dissection?
AB  - Dissection has long been the accepted method for teaching anatomy to medical
      students. More recently, some educators have suggested that easier, cheaper,
      alternative methods are just as effective. But what do the students think? This
      paper aimed to identify what undergraduate medical students learn, how they cope,
      and what effects participating in dissection has on them as individuals. A cohort
      of 267 second year medical students at Otago Medical School were invited to
      complete three online surveys; before their first dissection laboratory class,
      after their first musculoskeletal system dissection and following the last
      semester of studying anatomy. Open-ended questions showcasing the attitudes,
      beliefs, and opinions on what dissection had taught the medical students over
      years two and three were analyzed. A general inductive approach was used and
      common emergent themes were identified. In total, 194 students completed the
      second, and 108 students completed the third questionnaire. Students commonly
      conveyed dissection as an appropriate and valuable educational tool, useful for
      teaching and learning anatomical knowledge and relationships, appreciating the
      body in three-dimension, teamwork, and how to cope with death/dead bodies. The
      noted effects of personal growth while participating in dissection were highly
      varied, but in general, impacted positively on the majority of students. This
      study shows that at Otago Medical School the students also believe that
      dissection is not only a useful tool to learn anatomy but also that it fosters
      teamwork, assists professional development and helps them come to terms with
      death and dying. Anat Sci Educ 11: 325-335. (c) 2017 American Association of
      Anatomists.

PMID- 29205959
TI  - Maintenance and assessment of cell viability in formulation of non-sporulating
      bacterial inoculants.
AB  - The application of beneficial, plant-associated microorganisms is a sustainable
      approach to improving crop performance in agriculture. However, microbial
      inoculants are often susceptible to prolonged periods of storage and deleterious
      environmental factors, which negatively impact their viability and ultimately
      limit efficacy in the field. This particularly concerns non-sporulating bacteria.
      To overcome this challenge, the availability of protective formulations is
      crucial. Numerous parameters influence the viability of microbial cells, with
      drying procedures generally being among the most critical ones. Thus,
      technological advances to attenuate the desiccation stress imposed on living
      cells are key to successful formulation development. In this review, we discuss
      the core aspects important to consider when aiming at high cell viability of non
      sporulating bacteria to be applied as microbial inoculants in agriculture. We
      elaborate the suitability of commonly applied drying methods (freeze-drying,
      vacuum-drying, spray-drying, fluidized bed-drying, air-drying) and potential
      measures to prevent cell damage from desiccation (externally applied protectants,
      stress pre-conditioning, triggering of exopolysaccharide secretion, 'helper'
      strains). Furthermore, we point out methods for assessing bacterial viability,
      such as colony counting, spectrophotometry, microcalorimetry, flow cytometry and
      viability qPCR. Choosing appropriate technologies for maintenance of cell
      viability and evaluation thereof will render formulation development more
      efficient. This in turn will aid in utilizing the vast potential of promising,
      plant beneficial bacteria as sustainable alternatives to standard agrochemicals.

PMID- 29205961
TI  - HER2/HER3-positive metastatic salivary duct carcinoma in the pleural effusion: A
      case report.
AB  - Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and
      SDC patients tend to be older men, more commonly in advanced stage with a poorer
      prognosis. Although the cytological characteristics of SDC on fine-needle
      aspiration cytology have been well-described at the primary site, they have not
      been explored in metastasis. Here we reported a case of HER2/HER3-positive
      metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s
      who had undergone extended total parotidectomy in 2008. He was originally
      diagnosed as having HER2-positive left parotid SDC. Six years later a mass was
      discovered in the left lung by chest computed tomography (CT) and was diagnosed
      as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a
      recurrent SDC in the left pleural effusion and died of respiratory failure.
      Cytological findings from bronchial brushing smear showed small sheet clusters in
      a slightly necrotic background. In the pleural effusion cytology, tumor cells
      appeared as ball-like clusters of epithelioid cells with apocrine-like findings.
      In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly
      overexpressed relative to the matched primary tumor, even though HER2
      amplification did not change. Cytological findings and HER family receptors
      differed between the primary and metastatic SDC. Therefore, molecular tests, such
      as protein expression and gene amplification using cytological specimens, may
      become important in future when determining therapy strategies in patients with
      distant metastasis.

PMID- 29205962
TI  - [Genes Expression in the Early Stage of Acute Renal Ischemia-reperfusion Injury
      in Rats].
AB  - OBJECTIVES: To study the differential genes expression in the early stage of
      acute renal ischemia-reperfusion injury and explore potential molecular
      mechanisms. METHODS: The ischemia-reperfusion model was made via clamping renal
      artery of rat. The microarray detection and bioinformatics analyzing of the genes
      expression were performed. Differentially expressed genes were screened and
      related cellular activities and signaling pathways were analyzed in early stage
      of acute kidney injury. Meanwhile, molecules closely relative to acute kidney
      injury were explored by establishing a biological network of the differentially
      expressed genes, and the results were verified by real-time PCR. RESULTS: A total
      of 151 genes showed differential expression in this study, including 132 up
      regulated and 19 down-regulated genes. Cell proliferation, cytokines mediated
      signaling transduction and immune responses were greatly enriched by GO and KEGG
      analysis. The results of real-time PCR showed that compared with control groups,
      three selected genes (ANXA1, PHLDA1 and KLF6) which related to the acute kidney
      injury had an obvious differential expression in the early stage of disease. The
      multiple of increase was essentially the same as the multiple detected by
      microarray. CONCLUSIONS: This study shows differential gene expression profile,
      related biological processes and signaling pathways involved in the early stage
      of acute kidney injury. ANXA1, PHLDA1 and KLF6 may play a role in the
      pathogenesis of acute kidney injury.

PMID- 29205963
TI  - [Relationship between the Expression of alpha-syn and Neuronal Apoptosis in Brain
      Cortex of Acute Alcoholism Rats].
AB  - OBJECTIVES: To observe the changes of expression of alpha-synuclein (alpha-syn)
      and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore
      the mechanism of the damage caused by ethanol to the neurons. METHODS: The model
      of acute alcoholism rat was established by 50% alcohol gavage. The alpha-syn and
      caspase-3 were detected by immunohistochemical staining and imaging analysis at 1
      h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean
      of optical density were detected and the trend change was analyzed. The variance
      analysis and t-test were also performed. RESULTS: The number of alpha-syn
      positive cell and average optical density in brain cortex of acute alcoholism rat
      increased significantly and peaked at 6 hour with a following slight decrease at
      12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after
      poisoning, the number of caspase-3 positive cell and average optical density in
      brain cortex of rats gradually increased. CONCLUSIONS: The abnormal aggregation
      of alpha-syn caused by brain edema and hypoxia may participate the early stage of
      neuronal apoptosis in brain cortex after acute alcoholism.

PMID- 29205964
TI  - [Changes of HbCO in the Blood of Rats with Different CO Concentration and
      Inhalation Time].
AB  - OBJECTIVES: To explore the change rules of behavioral characteristics, survival
      time and saturation of carboxyhemoglobin (HbCO) in different CO concentration to
      provide experimental basis for the cases of CO poisoning death in forensic
      practice. METHODS: Total 160 SD rats were randomly divided into four groups. CO
      with the concentration of 1 250 mg/m3, 3 750 mg/m3, 6 250 mg/m3 were continuously
      and respectively replenished in a self-made toxicant exposure equipment until
      rats died from poisoning. In different CO concentration, the behavioral
      characteristics and survival time of poisoning rats were observed and recorded.
      The saturation of HbCO in heart blood was detected by spectrophotometric method.
      Organs such as brain, heart, lung and liver, and heart blood were obtained via
      autopsy and histopathological observation was performed. RESULTS: The behavioral
      characteristics of CO poisoning rats were limp and slow response. There were a
      gradual decrease of survival time and an increase of HbCO saturation in rats with
      the increase of CO concentration. Three rats in CO concentration of 1 250 mg/m3
      group showed lower saturations of HbCO than the lethal dose and this situation
      hasn't been found in other groups. CONCLUSIONS: The animal model of CO poisoning
      established under different CO concentration has the advantages such as
      simplicity and good repeatability, which lays a foundation to the further study
      for CO and other inhaled toxic gas in the research of forensic sciences.

PMID- 29205965
TI  - [Diatoms Distribution in Ningbo Three-river Watershed during Summer].
AB  - OBJECTIVES: To explore the species, quantity and distribution of diatoms in
      Ningbo three-river watershed during summer and to provide scientific basis for
      forensic examination of drowning cases in the waters of Ningbo. METHODS: Water
      samples were collected in July and August of 2015. Fourteen water sampling points
      were selected from the Yao River, the Fenghua River and the Yong River. The
      morphological features of diatom species and dominant diatoms were distinguished
      by microscope. RESULTS: A total of 16 species of diatoms were detected in the Yao
      River, the Fenghua River and the Yong River. Melosira was the dominant species in
      the Yao River, and the quantity and richness were higher than in other rivers.
      The richness of Cyclotella in the Yong River was higher than in other rivers. The
      richness of Pinnularia and Licmophora were higher in the Fenghua River than in
      the Yao River and the Yong River. CONCLUSIONS: The species and proportion of
      diatom is different in each river. Database of the species and relative
      composition for the diatoms in corresponding river is established, which may
      provide data support for forensic examination of drowning cases in Ningbo three
      river watershed.

PMID- 29205966
TI  - [Expression of XPG Gene in Forensic Age Estimation].
AB  - OBJECTIVES: To explore the expression of xeroderma pigmentosum complementation
      group G (XPG) gene in healthy Han population of different ages and to analysis
      the relationship between the mRNA and protein expression levels of XPG and age,
      which may provide a new molecular-biological indicator for forensic age
      determination. METHODS: Total 150 samples of peripheral blood were collected from
      healthy Han population of different ages. Total RNA of peripheral blood
      mononuclear cell (PBMC) were extracted by TRIzol method, and the relative
      expression of XPG mRNA in PBMC was detected by quantitative real-time PCR, and
      the protein expression levels of XPG in plasma were detected by ELISA. RESULTS:
      The mRNA and protein expression levels of XPG in <=18 years old group were
      significantly different from 19-45 years old group and >=46 years old group
      (P<0.05), while there was no significant difference between 19-45 years old group
      and >=46 years old group (P>0.05). No significant sex differences were observed
      in mRNA and protein expression levels of XPG (P>0.05). CONCLUSIONS: The relative
      expression level of XPG mRNA in PBMC declines with the increase of age in younger
      age, while the protein expression level in plasma increases with age, and XPG
      gene can be used as one of new markers for forensic age estimation.

PMID- 29205967
TI  - [Forensic Application of 16 X-STR Loci in Henan Han Population].
AB  - OBJECTIVES: To investigate the genetic data of 16 X-STR loci in Henan Han
      population and to assess the application value in forensic science. METHODS: The
      DNA of 326 unrelated individuals in Henan Han population were amplified using
      GoldeneyeTM DNA identification system 17X kit, and the PCR products were analyzed
      by electrophoresis through 3130xl genetic analyzer. The fragment sizes of alleles
      were analyzed subsequently by GeneMapper(r) ID-X. Allele frequencies and
      population genetics parameters of 16 X-STR loci were analyzed statistically and
      compared with the available data of other Han populations from different regions.
      RESULTS: Among the 16 X-STR loci, DXS6800 were found to be moderately polymorphic
      and the other 15 X-STR loci were highly polymorphic. The cumulative
      discrimination power in females and males were 0.999 999 999 999 992 and 0.999
      999 996 577 712, respectively. The combined power of exclusion in trios and in
      duos were 0.999 999 971 and 0.999 992 574, respectively. CONCLUSIONS: The 16 X
      STR loci meet the application requires of forensic genetics, especially for
      testing the special paternity cases.

PMID- 29205968
TI  - [Effect of the Chinese Herbal Medicinal Ingredients in Huoxiang Zhengqi Liquid on
      Alcohol Metabolism in Rats].
AB  - OBJECTIVES: To study the changes of alcohol content and pharmacokinetic parameter
      in rats after taking Huoxiang Zhengqi liquid. METHODS: The rats were randomly
      divided into three groups and given with white alcohol at the dose of 3.0 mL/kg,
      low-dose and high-dose Chinese medicine liquor, respectively. The blood was
      collected before administration and 5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 3 h,
      4 h, 5 h, 6 h and 8 h after administration by cutting rats' tails. The
      concentrations of alcohol in blood were detected by headspace-gas chromatography
      method. The main pharmacokinetic parameters were calculated by DAS 2.0, and then
      analyzed by SPSS 17.0. RESULTS: The difference of maximum blood concentrations
      between high-dose Chinese medicine alcohol group and white alcohol group was
      statistically significant (P<0.05). There was no significant difference in other
      pharmacokinetic parameters among three groups (P>0.05). CONCLUSIONS: The Chinese
      herbal medicinal ingredients in the Huoxiang Zhengqi liquid has no effect on the
      metabolism and elimination of ethanol in rats. The research provides useful
      reference for the qualitative assessment and processing of traffic accident cases
      involved in Huoxiang Zhengqi liquid and the studies related to drug-interaction.

PMID- 29205969
TI  - [Forensic Analysis of the Characteristics of Pelvic Fracture in 65 Road Traffic
      Accident Death Cases].
AB  - OBJECTIVES: To analyze the characteristics and mechanisms of pelvic fractures in
      the cases of road traffic accident deaths. METHODS: Total 65 cases of road
      traffic accident deaths with pelvic fracture were collected, and the sites,
      characteristics and injury mechanisms of pelvic fracture were statistically
      analyzed. RESULTS: Among the 65 cases of pelvic fracture, 38 cases of dislocation
      of sacroiliac joint were found, and most combined with pubis symphysis separation
      or fracture of pubis. In the fractures of pubis, ischium and acetabulum, linear
      fractures were most common, while comminuted fractures were most common in sacrum
      and coccyx fractures. There were 54 cases combined with pelvic soft tissue
      injury, and 8 cases with pelvic organ injury and 44 cases with abdominal organ
      injury. In the types of pelvic ring injury, 32 cases were separation, 49.32%,
      followed by compression, 26.15% and only one case was verticality, 1.54%.
      CONCLUSIONS: Detailed and comprehensive examination of the body and determination
      of the pelvic fracture type contribute to analyze the mechanisms of injury.

PMID- 29205970
TI  - [Retrospective Analysis of 17 Family Homicide Cases].
AB  - OBJECTIVES: To summarize the characteristics of family homicide cases and to
      provide reference for the analysis and prevention of such cases. METHODS:
      Seventeen solved family homicide cases in Liyang from 2004 to 2014 were
      investigated. The original registration information, record of scene
      investigation, corpse inspection report and case situation were analyzed
      statistically. RESULTS: The characteristics of the 17 family homicides cases
      showed that most victims were female and most suspects were male, and spouse
      infidelity and suspected spouse infidelity have higher proportion in the motives
      for the killings. Murders by patients with psychosis, camouflage murders and
      murder-suicides occupied a certain proportion in the family homicide cases.
      CONCLUSIONS: The family homicide cases are correlated with the family factors
      such as extramarital sexual intercourse and murder by patients with psychosis.
      Some suspects suicided after murder. The tools for committing crimes have the
      features of simplicity, randomness and easy source availability.

PMID- 29205971
TI  - [Analysis of the Injury-disease Relationship between Spondylolysis and Trauma in
      26 Forensic Identifications].
AB  - OBJECTIVES: To expound the injury-disease relationship between spondylolysis and
      trauma for the points of forensic identification. METHODS: Total 26 cases of
      spondylolysis were collected and the characteristics of this disease such as age,
      accompanied symptoms, treatment and injury manner were discussed. RESULTS: The
      causal relationship existed between trauma and injury consequence in 2 appraised
      individuals and both of them aged less than 50 years old. The injury manners of
      both were high-energy injury with combined injury and these 2 patients were
      treated by operation. CONCLUSIONS: The analysis of injury-disease relationship
      between spondylolysis and trauma should be paid attention in the middle-young age
      under 50 years old. More importantly, the injury-disease relationship should be
      analyzed in the patients who chose operative treatment.

PMID- 29205972
TI  - [Microdeletion and Mutation of Y Chromosome in Full Sibling Identification].
AB  - OBJECTIVES: To explore the identification method of full sibling between two
      males with microdeletion and mutation of Y chromosome. METHODS: DNA were
      extracted from two samples. The type testing of Y-STR and autosomal STR were
      performed. Full sibling between two individuals was calculated by IBS, ITO and
      discriminant functions methods. RESULTS: There were 2 loci mutations existed in
      33 Y-STR loci and one of the two samples had 19 loci deletions. The IBS of two
      samples was 53 and greater than the threshold which was 42; FSI was 1.36*1016 and
      far greater than 19. The discriminant function of full sibling-unrelated
      individual DFS2 was greater than DR2, which meant the two individuals tend to be
      full sibling. CONCLUSIONS: The methods of IBS, ITO and discriminant functions of
      full sibling-unrelated individual can be used comprehensively to provide more
      reliable expert opinion in microdeletion and mutation of Y chromosome in full
      sibling identification.

PMID- 29205973
TI  - [Application of COI Gene Mini-barcoding in Species Identification of Hair].
AB  - OBJECTIVES: To identify the species of mammalian hair using COI gene mini
      barcoding technology. METHODS: A pair of universal primers for mammalian COI gene
      mini-barcoding were designed. The hair DNA samples of experimental animals from
      11 species in 5 orders, mammalia was amplified by PCR technology with universal
      primers, and the PCR products were sequenced by bi-directional DNA and after the
      sequences splicing the results were deposited into the BOLD database to perform
      the homology comparison. RESULTS: The DNA of hair from all experiment animal
      species could be totally amplified by the mini-barcoding universal primers
      designed in this study. The length of amplified fragment was 147 bp. The result
      of homology comparison in the database showed that the closest matching species
      were consistent with the experiment animal species. In addition to the matching
      degree of Panthera leo (98.99%), all homology matching degree of the other
      experiment animals were 100%, and the intraspecific genetic distance of Panthera
      leo was 1%. The interspecific genetic distance was ten times more than the
      intraspecific genetic distance which could be used for species identification.
      CONCLUSIONS: The COI gene mini-barcode technology is established and can provide
      fast and accurate species identification for hair of mammals.

PMID- 29205974
TI  - [Research Progress on Estimation of Early Postmortem Interval].
AB  - Estimation of postmortem interval (PMI) is very important for judging the nature
      of cases, restricting the scope of investigation and suspect, which is always the
      emphasis and difficulty for forensic pathology. Early postmortem interval is the
      time between 0 and 24 hours after death. Due to the shorter time after the case
      occurred, precisely estimating early postmortem interval can help solve crimes,
      which has important significance in forensic medicine. In recent years, series of
      advanced methods and technologies are used to estimate the early PMI by the
      internal and overseas scholars who work in the forensic area. This paper reviews
      the research progress on fluids biochemistry, supravital reactions, metabolomics,
      imageology and the degradation rule of genetic material to provide a new idea to
      the study and application for estimation of early PMI.

PMID- 29205975
TI  - [Research Progress on Biomechanics of Craniocerebral Injury in Children].
AB  - In the researches of biomechanics for child craniocerebral injury, the research
      progress of performance parameter detection for brain, skull, cranial suture and
      dura mater, and the finite element model construction for child's head were
      reviewed. Meanwhile, the shortcomings of the established finite element model
      construction of child's head were analyzed. Thus, it is necessary to strengthen
      the material properties parameter detection of child's head, and establish the
      relevant database, so as to lay the foundation for establishing an accurate
      finite element model of child's head.

PMID- 29205976
TI  - [Research Progress of the Death Caused by Insulin Intoxication].
AB  - In recent years, with the sustained increase of the incidence of diabetes in
      humans and the wider use of exogenous insulin, the cases of inappropriate use and
      overdose of insulin is growing, even the cases of suicide and homicide using
      insulin. Through searching the literature at home and abroad about the mechanism,
      clinical and case report of poisoning and death caused by insulin intoxication,
      this paper reviews the mechanism, clinical manifestations, pathological changes,
      and forensic examination.

PMID- 29205977
TI  - Evaluation of combined effects of brain electronic biofeedback training and
      psycho-behavior intervention in ADHD affected children.
AB  - BACKGROUND: The present study aimed to explore the potential effects of brain
      electronic biofeedback training in combination with psycho-behavior intervention
      during non-medical treatment of children with attention deficit hyperactivity
      disorder (ADHD). METHODS: The children with ADHD admitted to our department from
      January 2015 to January 2016 were selected as the study subjects. All the cases
      met the standard of Chinese classification of mental disorders criterion and were
      divided into two groups, the control group and the observation group, with 15
      cases in each group. Medical treatment and brain electronic biofeedback training
      were provided for the children in the control group; while medical treatment and
      brain electronic biofeedback training in combination with psycho-behavior
      intervention were provided to children in the observation group. For both groups,
      one course lasted for three months, after which questionnaires were distribute in
      order to evaluate the application effects. RESULTS: The symptoms of the children
      in the two groups were improved after the treatment. However, the improvement in
      observation group was significantly higher that of the children in the control
      group. CONCLUSIONS: Brain electronic biofeedback training in combination with
      psycho-behavior intervention is significantly better treatment option for
      children affected with ADHD.

PMID- 29205978
TI  - Current views of pediatric amblyopia.

PMID- 29205979
TI  - Update on Current Care Guideline: Periodontitis.
AB  - Periodontitis is common in the adult Finnish population. Also the prevalence of
      peri-implant diseases increases. As symptoms are rare, affected patients seldom
      seek dental care but require attention through the health care system. A careful
      periodontal screening, including risk assessment, is essential. Individual
      brushing and interdental cleaning instructions, as well as tobacco counseling,
      are important in preventing and treating these diseases, Early signs of
      periodontitis are indication for treatment, including necessary maintenance
      visits, preventing the severe periodontitis and its harmful consequences for the
      patient's dentition and general health.

PMID- 29205980
TI  - Retinopathy of prematurity - from recognition of risk factors to treatment
      recommendations.
AB  - Retinopathy of prematurity is a proliferative retinal disorder diagnosed
      exclusively in prematurely born infants. In retinopathy of prematurity, growth of
      the retinal vasculature is disturbed, leading to hypoxia-induced pathological
      changes typical of retinopathy of prematurity, in the worst case resulting in
      retinal detachment. The most typical risk factors predisposing to the disease
      include hyperoxemia, low levels of insulin-like growth factor 1 (IGF-I), and low
      birth weight in relation to weeks of pregnancy. Laser therapy of peripheral
      retina is the currently established form of treatment. Screening is applied in
      order to recognize the pathological changes in retinopathy of prematurity early
      enough.

PMID- 29205981
TI  - Pregnancy and delivery after a cesarean section.
AB  - One out of seven of all parturients and one out of five primigravid women deliver
      by caesarean section. Of four women having undergone caesarean section, three
      will give birth vaginally, provided that the indication for surgery has been
      temporary by nature. Spontaneous beginning of labor and a previous vaginal
      delivery improve the chances of succesful of vaginal delivery. Rupture of the
      uterus in subsequent pregnancies is the most feared sequel to a caesarean
      section, with an occurrence of 0.2 to 1.5%. Delivery by caesarean is indicated in
      case of previous rupture of the uterus, hysterotomy through vertical incision,
      and more than two previous caesarean sections.

PMID- 29205982
TI  - Spasticity or periodic limb movements?
AB  - BACKGROUND: Spasticity and spasms are distressing features of the upper motor
      neuron syndrome (UMNS) following spinal cord injuries (SCI) or multiple sclerosis
      (MS), and have common therapeutic implications. Despite an increase of
      antispastic drugs and strategies, sometimes up to the surgical implant of
      intrathecal baclofen pump, some patients still complain of disabling spasms,
      which poses diagnostic and therapeutic challenges. Although clinically similar,
      flexor spasms due to pyramidal tract disruption must be clearly differentiated
      from periodic limb movements (PLM), often accompanying restless leg syndrome
      (RLS) and occurring during sleep. We raised the hypothesis of this differential
      as a diagnostic confusion in this particular population. AIM: The aim of this
      study was twofold: 1) to search for RLS with PLM in consecutive patients referred
      for uncontrolled disabling spasms despite treatment, by nocturnal polysomnography
      (PSG); 2) to report the efficacy of dopaminergic agonists on PLM in this
      population. DESIGN: Observational prospective study. SETTING: Spasticity Clinic
      at the Raymond-Poincare University Hospital, Garches, France. POPULATION: All
      consecutive patients with MS or SCI, referred to our spasticity clinic from March
      2014 to July 2016 for the management of persistent and disabling spasms despite
      treatment. Obvious daytime spasticity or flexor spasms were not considered. When
      spasms prevailed at evening, night, or in supine position, patients underwent a
      nocturnal PSG. METHODS: Patients were assessed for RLS by clinical interview and
      for PLM by PSG. Patients with confirmed PLM (>=15 per hour of sleep) were treated
      with low dosage of pramipexole (after an iron deficiency was ruled out) and
      reassessed by PSG the following night. RESULTS: Forty-five patients were
      included. All fulfilled RLS criteria, and PLMs were confirmed in 39 patients.
      Median PLM index, and related arousals were 45.9 (19.8-76.2) and 5.1 (1.5-15)
      events per hour respectively. Nine patients treated with pramipexole underwent an
      early second PSG which showed an improvement of PLM index and arousals (P=0.0007
      and P=0.01, respectively). CONCLUSIONS: In this princeps study, we demonstrated
      that in SCI and MS patients, "persistent spasms" inefficiently treated by
      antispastic drugs could in fact be PLM. Furthermore, we first reported the
      efficacy of dopaminergic agonists for PLM in an MS and SCI population. CLINICAL
      REHABILITATION IMPACT: This study brings new insights on abnormal movements,
      often misinterpreted as spasticity, and their management. We suggest to include a
      PSG in the diagnostic approach of uncontrolled spasms prevailing at night or in
      supine position, to search for PLM, which are easily treatable.

PMID- 29205983
TI  - Treatment of proximal humerus fractures in the elderly.
AB  - A proximal humerus fracture typically occurs when an elderly woman falls directly
      onto her shoulder or on her outstretched arm. Local pain in the shoulder and
      immobility of the upper arm raise a suspicion of a significant injury. Other bone
      and tendon injuries in the shoulder region as well as dislocation of the shoulder
      should be considered on differential diagnosis. Diagnosis is achieved by plain X
      ray. Most fractures can be treated conservatively. Consultation with an
      orthopedist is needed, if there are several fracture fragments with extensive
      dislocation.

PMID- 29205984
TI  - Liver trauma in a young woman.
AB  - A young woman fell off a horse, leaving her right flank contused by a hoof. This
      resulted in a severe liver trauma that seemed to require surgical treatment.
      After fluid resuscitation and five units of red blood cells the patient's status,
      however, stabilized upon entering the operating room. The operation was avoided,
      but intensive care follow-up was continued for six days. The patient made a
      complete recovery. Conservative treatment of liver trauma is successful in 90% of
      mild and almost 70% in severe traumas.

PMID- 29205985
TI  - Current Care Guideline: Age-related macular degeneration (AMD).
AB  - Age-related macular degeneration (AMD) is the main cause of visual impairment in
      developed countries. Several improvements in the visualization of posterior
      segment of the eye together with the introduction of intravitreal anti-VEGF
      treatment have revolutionized the prognosis of the wet form of AMD (wAMD).
      Increasing incidence of wAMD together with the limited resources of the
      healthcare systems pose challenges for the provision and development of care. In
      context of these current aspects, we aim to set evidence-based guidelines for
      diagnosis, treatment and follow-up of patients with wAMD.

PMID- 29205986
TI  - Acute pericarditis.
AB  - Acute pericarditis is typically associated with a viral infection. Chest pain
      appearing in connection with or soon after the symptoms of infection is the
      characteristic symptom. Diagnosis is based on the recognition of two
      characteristic findings (pericardial chest pain, pericardial friction rub, new
      ECG changes or new pericardial effusion). Medication with an anti-inflammatory
      analgesic for 1 to 2 weeks is the first-line treatment. A longer course of
      colchicine is recommended for the prevention of recurrence of the disease. The
      use of glucocorticoids should be avoided due to the associated risk of
      recurrence. Exercise and physical activity are harmful during pericarditis.

PMID- 29205987
TI  - Recurrent pericarditis.
AB  - Recurrent pericarditis is the most common and problematic complication of acute
      pericarditis. After acute pericarditis, the pericarditis recurs in 20 to 50% of
      the patients. In most cases the etiology of pericarditis remains unclear,
      although it is generally thought to arise by an immunological mechanism. NSAID
      medication in combination with colchicine is the cornerstone of the treatment.
      Corticosteroids should be used mainly for those in whom the first-line drug
      treatment is not sufficient or first-line treatments are contraindicated.

PMID- 29205988
TI  - Pericardial fluid: assessment and examination.
AB  - Pericardial fluid is a common finding on echocardiography. Less than 10 mm of
      fluid on ultrasound scan is not necessarily associated with any significant
      illness. Clinical examination, blood count, renal and liver enzymes and thyroid
      function tests as well as inflammatory marker tests are often adequate for a
      patient who is in good health. A significant amount of fluid requires further
      investigations, especially in a symptomatic patient. Cancers, infections and
      various systemic diseases are the most common causes of prominent effusion.

PMID- 29205989
TI  - Postpericardiotomy syndrome.
AB  - Postpericardiotomy syndrome (PPS) is a common complication following cardiac
      surgery. In most cases it develops 2 to 3 weeks after the operation. An
      inflammatory reaction develops in the pericardium or pleural space with fever,
      chest pain and dyspnea as typical symptoms. The disease process is usually self
      limiting. At present, the etiology is unknown, but an immunological mechanism is
      suspected as the cause of the disease. The incidence of PPS is essentially
      dependent on diagnostic criteria, patient group and type of operation. Treatment
      is carried out with anti-inflammatory analgesics, combined with colchicine in
      more severe cases.

PMID- 29205990
TI  - Pericardial drainage and sampling.
AB  - Invasive treatment of pericardial effusion comes into question when the volume of
      liquid in the pericardium limits the pumping action, the cause of effusion is
      unclear, the response to conservative treatment has been poor, or administration
      of a drug into the pericardium is desired. A number of surgical means or puncture
      techniques are available for pericardial drainage. We present the indications and
      modes of treatment for invasive treatment of pericardial effusion. Thrombi, pus
      or air may also occasionally be present in the pericardium, limiting the heart's
      pumping action.

PMID- 29205991
TI  - Cardiac deformation imaging.
AB  - Deformation imaging (strain imaging) is an echocardiographic method for
      evaluating myocardial function that is also suitable for clinical use. There are
      two deformation imaging techniques: Tissue Doppler and 2D strain (speckle
      tracking). Deformation imaging allows the measurement of regional myocardial
      deformation in three dimensions. Longitudinal deformation (strain) measures
      longitudinal myocardial fiber contraction, and reflects subendocardial myocardial
      function, which is usually the first to deteriorate in patients with heart
      disease. Reduced longitudinal strain can reveal heart disease even when ejection
      fraction and cardiac contractility appear normal. Deformation imaging can be used
      for diagnosing ischemia, distinguishing between pathological and physiological
      hypertrophy, and early detection of heart disease in hypertension or diabetes.
      Global longitudinal strain (GLS) is an indicator of overall left ventricular
      systolic function, and correlates with the prognosis better than ejection
      fraction.

PMID- 29205992
TI  - Curative effect of knee arthroplasty on patients with osteoarthritis and analysis
      of long-term joint function of these patients.
AB  - BACKGROUND: We aimed to explore the curative effect of knee arthroplasty on
      patients with osteoarthritis and analysis of their long-term joint function.
      METHODS: 96 cases of osteoarthritis patients, collected in our hospital from June
      2010 to May 2011, were divided into control group and observation group (n=48,
      each group). Patients in observation group were treated by knee replacement, and
      patients in control group were treated by arthroscopic debridement. Bleeding
      during operation of patients and the operation time in both groups were
      comparable during their followed up for 6~60 months, with an average of 52
      months. Neer score was used to compare the curative effect of patients after 6
      months; knee society score (KSS) was used to compare knee joint function and knee
      joint of motion (ROM) of patients several days prior to surgery and after 6
      months, 12 months, 24 months, and 48 months. Visual analogue scale (VAS) was used
      to compare pain degrees of patients at the last follow-up. RESULTS: By Neer score
      comparison, after 6 months excellent and good rate of pa in observation group
      (91.67%) was obviously highe than that of control group 70.83% (P<0.05); ROM of
      patients in observation group was obviously higher than that in control group
      (P<0.05); after six months, KSS score of patients in both groups greatly
      improved. As well, with the extension of time, their knee joint function showed a
      better trend, and KSS score of patients in observation group was obviously higher
      than that of control group (P < 0.05). Pain of patients in observation group was
      significantly lower than that in control group (P<0.05). CONCLUSION: Both the
      arthroscopy debridement and the knee replacement have good curative effect. The
      curative effect of knee replacement was better, postoperative knee joint activity
      was obviously improved, the long-term recovery of knee joint function was good,
      and knee replacement can reduce the pain of the patients.

PMID- 29205993
TI  - Should patients with schizophrenia receive antidepressants?
AB  - Antipsychotics play a key role in the pharmacological treatment of schizophrenia,
      and monotherapy is effective for most patients. Achieving an optimal treatment
      response is, however, often difficult. Combining an antidepressant drug to the
      antipsychotic regimen could potentially improve treatment outcomes, although the
      evidence supporting the use of such combinations is limited and contradictory.
      Positive evidence has mostly been obtained from the efficacy of antidepressants
      acting on monoamine receptors on the negative symptoms of schizophrenia. These
      receptor-active drugs may also improve cognition in schizophrenic patients. In
      the light of current knowledge, antidepressants do not appear to potentiate the
      psychotic symptoms of schizophrenic patients. However, there is no robust
      evidence of the efficacy of antidepressants in the treatment of schizophrenia
      related depression, and thus monotherapy with an antipsychotic drug is
      recommended for treating it. If using antidepressants in addition to
      antipsychotics is deemed necessary, the risk of pharmacodynamic and
      pharmacokinetic interactions should be kept in mind.

PMID- 29205994
TI  - Allergic rhinitis.
AB  - There have been no major changes in the pharmacological treatment of allergic
      rhinitis in recent years. Treatment is symptomatic and tailored individually,
      taking into account the type and severity of symptoms. Few new products have
      entered the market, and treatment is still largely based on antihistamines and
      nasally administered glucocorticoids. However, the general strategies for
      treating allergic rhinitis have developed over the last decade due to the
      introduction of the Finnish National Allergy Program. The treatment should aim at
      improving tolerance. Avoiding allergens is not necessary but it may help in
      controlling the symptoms. Hyposensitization, the only disease-modifying therapy,
      is a recommended, effective and safe form of treatment. New, practical sublingual
      hyposensitization products have facilitated treatment implementation and moved it
      from outpatient clinics into homes, which is a more patient-oriented approach and
      also cost-effective in the long term. However, the unit costs of treatment are
      relatively high for the patients.

PMID- 29205996
TI  - Current management of ovarian endometriomas.
AB  - The choice of treatment in case of ovarian endometriomas is one of the most
      discussed topics in Reproductive Medicine. Management options include expectancy,
      medical treatment, surgery, in vitro fertilization (IVF), or a combination of the
      above. The main presenting symptom, i.e. pain or infertility, usually guide the
      choice of treatment. Medical treatment is usually preferred as the first line
      option when pain is the associated symptom, whereas surgery or IVF are preferred
      in case of associated infertility. In most cases, however, the symptoms may
      overlap, and often a patient with infertility complains also of chronic pelvic
      pain, and vice versa. In addition, in many cases the patient may be asymptomatic,
      usually presenting with the incidental diagnosis of an ovarian endometrioma.
      Therefore, a strict categorization in two separate pathways of either associated
      pain or associated infertility, as the one outlined in current guidelines, may
      not represent the real clinical scenario. In this context, a personalized
      approach, taking into account several additional variables that are not
      considered in guidelines, is mandatory. In the present review, a symptom-driven
      approach to the management of ovarian endometriomas, that goes beyond the
      pain/infertility categorization, is described, considering additional parameters
      that guide the choice of treatment, with a patient-centered, personalized
      approach.

PMID- 29205997
TI  - Who would benefit from exome sequencing?
AB  - Next-generation sequencing methods have revolutionized the possibilities for
      analyzing the human genome. Sequencing the exome, the protein-encoding portion of
      the genome, is used, in clinical medicine, especially in the diagnosis of rare
      hereditary diseases, congenital developmental disorders and cancer. Using exome
      sequencing as a diagnostic test is justified when the results could lead to an
      accurate diagnosis, significantly influence the treatment and genetic counseling.
      It is a reliable method for detecting single base mutations as minor deletions
      and insertions.  However, with current methods the reliable analysis of larger
      changes in the number of copies, the length or repeats and areas present in
      multiple copies in the genome is challenging. Every human has many mutations in
      their exome, and distinguishing between insignificant and pathogenic mutations is
      thus a key challenge when interpreting the results of exome sequencing.

PMID- 29205995
TI  - Volume and health outcomes: evidence from systematic reviews and from evaluation
      of Italian hospital data.
AB  - BACKGROUND Improving quality and effectiveness of healthcare is one of the
      priorities of health policies. Hospital or physician volume represents a
      measurable variable with an impact on effectiveness of healthcare. An Italian law
      calls for the definition of "qualitative, structural, technological, and
      quantitative standards of hospital care". There is a need for an evaluation of
      the available scientific evidence in order to identify qualitative, structural,
      technological, and quantitative standards of hospital care, including the volume
      of care above or below which the public and private hospitals may be accredited
      (or not) to provide specific healthcare interventions. OBJECTIVES To identify
      conditions/interventions for which an association between volume and outcome has
      been investigated. To identify conditions/interventions for which an association
      between volume and outcome has been proved. To analyze the distribution of
      Italian health providers by volume of activity. To measure the association
      between volume of care and outcomes of the health providers of the Italian
      National Health Service (NHS). METHODS Systematic review An overview of
      systematic reviews was performed searching PubMed, EMBASE, and The Cochrane
      Library up to November 2016. Studies were evaluated by 2 researchers
      independently; quality assessment was performed using the AMSTAR checklist. For
      each health condition and outcome, if available, total number of studies,
      participants, high volume cut-off values, and metanalysis have been reported.
      According to the considered outcomes, health topics were classified into 3
      groups: positive association: a positive association was demonstrated in the
      majority of studies/participants and/or a pooled measure (metanalysis) with
      positive results was reported; lack of association: both studies and/or
      metanalysis showed no association; no sufficient evidence of association: both
      results of single studies and metanalysis do not allow to draw firm conclusions
      on the association between volume and outcome. Analysis of the distribution of
      Italian hospitals by volume of activity and the association between volume of
      activity and outcomes: the Italian National Outcome evaluation Programme 2016 The
      analyses were performed using the Hospital Information System and the National
      Tax Register (year 2015). For each condition, the number of hospitals by volume
      of activity was calculated. Hospitals with a volume lower than 3-5 cases/year
      were excluded. For conditions with more than 1,500 cases/year and frequency of
      outcome >=1%, the association between volume of care and outcome was analyzed
      estimating risk-adjusted outcomes. RESULTS Bibliographic searches identified 80
      reviews, evaluating 48 different clinical areas. The main outcome considered was
      intrahospital/30-day mortality. The other outcomes vary depending on the type of
      condition or intervention in study. The relationship between hospital volume and
      outcomes was considered in 47 out of 48 conditions: 34 conditions showed evidence
      of a positive association; * 14 conditions consider cancer surgery for bladder,
      breast, colon, rectum, colon rectum, oesophagus, kidney, liver, lung, ovaries,
      pancreas, prostate, stomach, head and neck; * 11 conditions consider
      cardiocerebrovascular area: nonruptured and ruptured abdominal aortic aneurysm,
      acute myocardial infarction, brain aneurysm, carotid endarterectomy, coronary
      angioplasty, coronary artery bypass, paediatric heart surgery, revascularization
      of lower limbs, stroke, subarachnoid haemorrhage; * 2 conditions consider
      orthopaedic area: knee arthroplasty, hip fracture; * 7 conditions consider other
      areas: AIDS, bariatric surgery, cholecystectomy, intensive care unit, neonatal
      intensive care unit, sepsis, and traumas; for 3 conditions, no association was
      demonstrated: hip arthroplasty, dialysis, and thyroidectomy. for the remaining 10
      conditions, the available evidence does not allow to draw firm conclusions about
      the association between hospital volume and considered outcomes: surgery for
      testicular cancer and intracranial tumours, paediatric oncology, aortofemoral
      bypass, cardiac catheterization, appendectomy, colectomy, inguinal hernia,
      respiratory failure, and hysterectomy. The relationship between volume of
      clinician/surgeon and outcomes was assessed only through the literature re view;
      to date, it is not possible to analyze this association for Italian health
      provider hospitals, since information on the clinician/surgeon on the hospital
      discharge chart is missing. The literature found a positive association for 21
      conditions: 9 consider surgery for cancer: bladder, breast, colon, colon rectum,
      pancreas, prostate, rectum, stomach, and head and neck; 5 consider the
      cardiocerebrovascular area: ruptured and nonruptured abdominal aortic aneurysm,
      carotid endarterectomy, paediatric heart surgery, and revascularization of the
      lower limbs; 2 consider the orthopaedic area: knee and hip arthroplasty; 5
      consider other areas: AIDS, bariatric surgery, hysterectomy, intensive care unit,
      and thyroidectomy. The analysis of the distribution of Italian hospitals
      concerned the 34 conditions for which the systematic review has shown a positive
      volume-outcome association. For the following, it was possible to conduct the
      analysis of the association using national data: unruptured abdominal aortic
      aneurysm, coronary angioplasty, hip arthroplasty, knee arthroplasty, coronary
      artery bypass, cancer surgery (colon, liver, breast, pancreas, lung, prostate,
      kidney, and stomach), laparoscopic cholecystectomy, hip fracture, stroke, acute
      myocardial infarction. For these conditions, the association between volume and
      outcome of care was observed. For laparoscopic cholecystectomy and surgery of the
      breast and stomach cancer, the association between the volume of the discharge (o
      dismissal) operating unit and the outcome was analyzed. The outcomes differ
      depending on the condition studied. The shape of the relationship is variable
      among different conditions, with heterogeneous slope of the curves. DISCUSSION
      For many conditions, the overview of systematic reviews has shown a strong
      evidence of association between higher volumes and better outcomes. The quality
      of the available reviews can be considered good for the consistency of the
      results between the studies and for the strength of the association; however,
      this does not mean that the included studies are of good quality. Analyzing
      national data, potential confounders, including age and comorbidities, have been
      considered. The systematic review of the literature does not permit to identify
      predefined volume thresholds. The analysis of national data shows a strong
      improvement in outcomes in the first part of the curve (from very low to higher
      volumes) for most conditions. In some cases, the improvement in outcomes remains
      gradual or constant with the increasing volume of care; in other, the analysis
      could allow the identification of threshold values beyond which the outcome does
      not further improve. However, a good knowledge of the relationship between
      effectiveness of treatments and costs, the geographical distribution and the
      accessibility to healthcare services are necessary to choose the minimum volumes
      of care, under which specific health procedures could not been provided in the
      NHS. Some potential biases due to the use of information systems data should also
      be considered. The different way of coding among hospitals could lead to a
      different selection of cases for some conditions. Regarding the definition of the
      exposure (volume of care), a possible bias could result from misclassification of
      health providers with high volume of activity. Performing the intervention in
      different departments/ units of the same hospital would result in an
      overestimation of the volume of care measured for hospital rather than for
      department/unit. For the conditions with a further fragmentation within the same
      structure, the association between volumes of discharge department and outcomes
      has also been evaluated. In this case, the two curves were different. The limit
      is to attribute the outcome to the discharge unit, which in case of surgery may
      not be the intervention unit. A similar bias could occur if the main determinant
      of the outcome of treatment was the caseload of each surgeon. The results of the
      analysis may be biased when different operators in the same hospital/unit carried
      out the same procedure. In any case, the observed association between volumes and
      outcome is very strong, and it is unlikely to be attributable to biases of the
      study design. Another aspect on which there is still little evidence is the
      interaction between volume of the hospital and of the surgeon. A MEDICARE study
      suggests that in some conditions, especially for specialized surgery, the effect
      of the surgeon's volume of activity is different depending on the structure
      volume, whereas it would not differ for some less specialized surgery conditions.
      The data here presented still show extremely fragmented volumes of both clinical
      and surgical areas, with a predominance of very low volume structures. Health
      systems operate, by definition, in a context of limited resources, especially
      when the amount of resources to allocate to the health system is reduced. In such
      conditions, the rationalization of the organization of health services based on
      the volume of care may make resources available to improve the effectiveness of
      interventions. The identification and certification of services and providers
      with high volume of activity can help to reduce differences in the access to non
      effective procedures. To produce additional evidence to guide the reorganization
      of the national healthcare system, it will be necessary to design further primary
      studies to evaluate the effectiveness and safety of policies aimed at
      concentrating interventions in structures with high volumes of activity.

PMID- 29205998
TI  - Diabetic nephropathy in type 1 diabetes.
AB  - Diabetic nephropathy (DN) also named diabetic kidney disease (DN) is one of the
      leading causes of mortality in people with diabetes. The aim of this review is to
      update the medical literature, the theories behind its early natural history, the
      pathways of its pathogenesis, its diagnosis and treatment. Poor glycemic control,
      hyperlipidemia, smoking, oxidative stress, accumulation of advanced glycated end
      products, environmental, genetic and epigenetic factors play an important role in
      the pathophysiological development of DN. Microalbuminuria has been traditionally
      used as the primary early diagnostic marker of microvascular complication
      unraveling the risk for progress to severe cardiorenal outcomes, but its
      prognostic role has been recently debated. The disease often leads to end-stage
      renal disease and it is often associated with major cardiovascular outcomes. Its
      early diagnosis is crucial for the patients in order to have a chance for proper
      treatment.

PMID- 29205999
TI  - Treatment of acute Achilles tendon ruptures in Central Finland Central Hospital
      in 2010-2015.
AB  - BACKGROUND: The epidemiology of Achilles tendon ruptures and treatment strategies
      have undergone a major change in recent years. We investigated the incidence of
      acute Achilles tendon ruptures, the choice of treatment strategies and treatment
      implementation. MATERIALS AND METHODS: The research material consisted of
      patients living in the catchment area of Central Finland Hospital District who
      had been diagnosed with an acute Achilles tendon rupture between 2010 and 2015.
      RESULTS: The final sample consisted of 266 patients. Conservative treatment was
      started for 207 patients, and the remaining 59 were referred for surgery. During
      the study period, the proportion of patients undergoing surgery fell from 41% to
      10%. Three patients (1.4%) were referred for surgery during conservative
      treatment, and 10 patients (4.7%) developed deep vein thrombosis while wearing a
      cast or an orthosis. Twelve patients (5.8%) sustained a re-rupture after
      conservative treatment. Two surgically-treated patients (3.5%) sustained a re
      rupture, and one patient (1.7%) developed deep vein thrombosis. CONCLUSIONS: The
      strategies for treating acute Achilles tendon ruptures have clearly become more
      conservative in our hospital. Conservative treatment is safe and rarely fails.
      However, it is important to bear in mind that surgery still has a role in the
      treatment of acute Achilles tendon ruptures.

PMID- 29206000
TI  - Dislocation of cochlear implant magnet as a complication following MRI.
AB  - According to current best knowledge, an MRI scan can be performed for patients
      with cochlear implants. The warnings and recommendations of the implant
      manufacturers must be followed strictly to prevent complications, such as
      overheating, migration or demagnetization of the magnet in the implant. We report
      on a case of cochlear implant magnet dislocation as a complication for an MRI
      scan. The patient had a tight bandage around the head to hold the magnet in place
      as recommended by the manufacturer, but apparently the bandage was not in the
      correct place.

PMID- 29206001
TI  - Current care guideline: Patient exposed to moisture damage.
AB  - Moisture damages and dampness in buildings is a risk factor for respiratory
      symptoms and development of asthma. Diagnostics and care of the patients must be
      based on general guidelines, regardless of potential moisture damage in home or
      work place. No laboratory or other clinical tests exist that can be used to
      associate potential moisture damage to perceived symptoms of the patient.
      Buildings affected by moisture damages should be remediated, because it is likely
      to be beneficial to health of the occupants and other users and for the condition
      of the building.

PMID- 29206002
TI  - Psychiatry in the first Francoist period: knowledge and practices for a <<New
      State>>.

PMID- 29206003
TI  - Outcomes and challenges in modern AAA repair: an introduction.

PMID- 29206004
TI  - Outcomes of endovascular aortic repair in the modern era.
AB  - Monitoring outcomes following endovascular aortic repair (EVAR) is critical.
      Although evidence from randomized controlled trials has solidified the role of
      EVAR, the analysis of outcomes and "real-world" data has uncovered limitations,
      improved the selection of appropriate patients, and underscored the importance of
      instructions for use. Subsequent studies demonstrated the learning curve of EVAR
      and gradual improvement of outcomes over time. Outcomes analyses will continue to
      play an important role, particularly as technological growth of endovascular
      therapy has enabled treatment of more complex aneurysm pathologies and patients.
      The important analyses are herein reviewed, following the development of EVAR in
      the treatment of intact abdominal aortic aneurysms (AAA) to ruptured AAAs, and
      finally to complex aneurysms, including thoracoabdominal aortic aneurysms and
      mycotic aneurysms. This includes an overview of the more recent results from
      analyses of branched and fenestrated EVAR, as well as the use of chimney grafts.
      It is emphasized that the success of endovascular repair has paradoxically been
      hampered by its rapid growth and early achievements. Even the most advanced
      engineering developments cannot overcome the long-term effects of the progression
      of aortic disease. The long-term benefits thus require careful planning and
      considerations of the natural history of aneurysms and the life expectancy of the
      patient. Large and international data registry collaborations should continue to
      play a role in providing outcomes analyses to guide future improvements.

PMID- 29206005
TI  - Expanding the indications for transcatheter aortic valve implantation: is it time
      to treat low risk patients?

PMID- 29206006
TI  - The beginning of Francoist psychiatry: the National Neurology and Psychiatry
      Conference (Barcelona, 1942).
AB  - While there has been some research into Francoist psychiatry, much work still
      needs to be done on the reorganization of the mental health profession within the
      new state. Held in Barcelona on 12, 13 and 14th January 1942, the National
      Neurology and Psychiatry Conference undoubtedly played a major role in the
      attempt to overthrow the dominant ideas in the field of Spanish psychiatry and
      displace its most influential figures. This article seeks to analyse the
      Conference's main organizational features and examine its most significant
      content, with the aim of evaluating its strategic importance in the context of
      both the psychiatrists' professional and scientific interests and their
      ideological and political concerns. Conference papers tackled issues such as
      neurology and psychiatry in wartime, vitamin deficiency and the nervous system,
      and new psychiatric treatments, including shock therapy. The Conference's marked
      ideological nature represented the beginning of a new professional dynamic,
      featuring the emergence or establishment of new leaders intent on laying the
      foundations of psychiatry during the early years of the Franco regime.

PMID- 29206007
TI  - Christian psychopathology: psychiatry and knowledge for the sake of salvation in
      the early years of Francoism.
AB  - After World War II came to an end, General Franco's regime attempted to step
      aside from the defeated fascist states by emphasizing its Catholic character. The
      change of image culminated in 1947 with the establishment of Spain as a Catholic
      State by means of the Law of Succession. This process generated the national
      catholic ideology, which became, during the first decades of the dictatorship,
      the hegemonic instrument for the transformation of Spanish society in an anti
      modernizing way. Scientific activity was not excluded from these changes, and a
      Catholic science conveying universal values and in harmony with the faith was
      strongly encouraged. One example of this Catholic science was the psychiatric
      approach developed by Juan Jose Lopez Ibor during the first Francoist period,
      including the concepts of anagogy, the perfection instinct, psychagogy and, above
      all, anxious thymopathy and life anguish. This paper analyses the Christian
      background of these notions, their scientific repercussions and their social
      utility for the dictatorship. This paper emphasizes the consideration of these
      key notions of Spanish psychiatry during the First Francoism as knowledge of
      salvation, i.e., as conveyors of assumed eternal values in accordance with the
      prevailing view of Catholicism. On the other hand, it points to the functioning
      of these concepts as a part of the regulatory network designed and deployed by
      Francoism to promote submission and resignation in the Spanish population.

PMID- 29206008
TI  - Mental hygiene in early Francoism: from racial hygiene to the prevention of
      mental illness  (1939-1960).
AB  - In this paper, we study the ideological bases of mental hygiene, understood as
      racial and moral hygiene, during the first years of Franco's regime and their
      evolution until 1960. First, we discuss the conceptualization of mental hygiene
      in the 1940s and its role as a tool for the legitimization of dictatorship,
      revealing the involvement of orthodox Catholicism and its links with moral and
      racial hygiene. Second, we assess the transformation of mental hygiene during the
      1950s towards modernization and a stronger linkage with the dominant trends of
      contemporary psychiatry without ever leaving the ideological background of
      Catholicism. For this purpose, we will focus on analysis of the activities of the
      Mental Hygiene Week held in Barcelona in 1954 and on the creation in 1955 of the
      National Board of Psychiatric Care, which took on mental hygiene as one of its
      functions. This paper shows the close relationship of mental hygiene during the
      early years of Francoism with the political principles of the Dictatorship. The
      1940s witnessed the deployment of a harsh discourse in which mental hygiene was a
      tool for the (moral and spiritual) education of the Spanish people in the
      political principles of the "New State", pathologizing political dissent and
      ideologically purifying the country. In the 1950s, Francoist mental hygiene
      underwent a process of aggiornamento marked by international political events
      following the defeat of fascism in World War II, advancing a project for
      (authoritarian) modernization in an international context already directed
      towards mental health.

PMID- 29206009
TI  - Hydrotherapy and medical entrepreneurship: the "water spell" of Ricardo Jorge.
AB  - Between 1886 and 1893, the doctor and hygienist Ricardo Jorge was linked to a
      commercial and medical project on the waters of GerAas. Known for many centuries
      and used for therapeutic purposes, they were administered on an empirical basis.
      When new chemical analyses were first published, the empirical properties of
      these waters took on a new role in hydrotherapy based on their now proven mineral
      and medicinal qualities. The article discusses in detail Ricardo Jorge's business
      venture, framing it in the context of the economic collection and treatment
      potential of mineral waters and the revival of the phenomenon of hydrotherapy,
      legitimized by new developments in the chemical analysis of waters. The
      commercial failure to exploit the water resources highlights the difficulties of
      this project and the complexity of the professional practice of hydrological
      medicine, although it resulted in a strengthening of Ricardo's authority and
      prestige in the field of hydrotherapy.

PMID- 29206010
TI  - Regulation, circulation and distribution of penicillin in Portugal (1944-1954).
AB  - Portugal did not participate in World War II but was one of the first countries
      in the world to receive penicillin for civilian use. The Portuguese Red Cross
      began to import the antibiotic from the United States of America in 1944 and
      appointed a controlling committee to oversee its distribution, due to the small
      amount available. In 1945, as world production increased, penicillin began to be
      distributed through the normal channels. An important role in its regulation was
      played by the official department responsible for controlling pharmaceutical and
      chemical products in Portugal, the Comissao Reguladora dos Produtos Quimicos e
      Farmaceuticos (Regulatory Committee for Chemical and Pharmaceutical Products).
      Penicillin was imported as a raw material from 1947 and the first medicaments
      containing penicillin, prepared in Portugal, were released into the commercial
      circuit in 1948. A laboratory had been established in 1942 by the Comissao
      Reguladora for the analytical verification of medicaments and medicinal products
      with the aim of certifying their quality and minimizing the number of products
      with no attested therapeutic efficacy. The number of medicaments analysed by this
      laboratory increased substantially from 72 in the year of its foundation (1942)
      to 2478 in 1954, including, after 1948, medicaments containing penicillin. The
      aim of the present paper was to elucidate the role of the Comissao Reguladora dos
      Produtos Quimicos e Farmaceuticos in regulating and controlling the distribution
      of penicillin in Portugal during the 1940s and 1950s.

PMID- 29206012
TI  - Letters: In Your Own Words.

PMID- 29206011
TI  - Santa's Sepsis Summit: A thermic analysis from the man who sees everything.

PMID- 29206013
TI  - Saving Pets, Too!

PMID- 29206014
TI  - Prolonged Kneeling: Why can't your patient get up from a kneeling position?

PMID- 29206015
TI  - Gastric and Small Bowel Tumors.
AB  - The incidence of gastric adenocarcinoma has decreased in the United States over
      the past 70 years although it continues to have a poor prognosis. While radical
      resection was initially the primary treatment for adenocarcinoma of the stomach,
      systemic chemotherapy and radiation have been shown to play a role in prolonging
      survival in most patient populations. This chapter explores the evidence that
      guides treatment for gastric cancer today. It also discusses the treatment for
      gastrointestinal stromal tumors (GIST), and small bowel tumors. In addition to
      systemic therapies, this chapter explores the surgical management of gastric and
      small bowel tumors including the extent of the gastric lymph node dissection.

PMID- 29206016
TI  - Behavior Zones: When to console, coach or reprimand a trainee.

PMID- 29206018
TI  - Suspect and Detect? Lactate levels may miss sepsis.

PMID- 29206017
TI  - Pathologic Features of Esophageal and Gastric Malignancies.
AB  - Esophageal and gastric carcinomas affect millions of individuals worldwide,
      placing a considerable burden on society. Unfortunately, preventative medicine
      falls short as screening methods for the upper gastrointestinal tract lack the
      ability to detect early onset disease. The overwhelming majority of cases present
      after symptoms appear when individuals have advanced disease with a poor
      prognosis.  Further complicating matters, the anatomic location of these
      neoplasms engenders rapid tumor progression, which repeatedly thwarts successful
      surgical treatment.  This chapter will focus on the pathological features of
      malignant neoplasms of the esophagus and stomach.

PMID- 29206019
TI  - Pathologic Features of Miscellaneous Foregut Malignancies.
AB  - In addition to tumors arising from the primary mucosal epithelium, the foregut is
      host to a variety of non-epithelial precursor cells which may give rise to
      neoplasms of neuroendocrine, mesenchymal, and hematolymphoid lineages. Many of
      these lesions also occur outside of the gastrointestinal tract, such as the
      extranodal lymphomas and many of the sarcomas, and in many cases share the
      features of their non-alimentary counterparts. This heterogeneous collection of
      malignancies features a wide spectrum of clinical presentations, morphologic and
      histopathologic features, genetic underpinnings, and treatment considerations.
      Although encountered less frequently than primary carcinomas, it is important to
      correctly recognize and classify these lesions to effectively manage and
      prognosticate the patients in which they occur. In this chapter, we focus on the
      clinical, morphologic, and genetic features of the primary esophageal and gastric
      neoplasms of neuroendocrine, mesenchymal, and lymphoid origin.

PMID- 29206020
TI  - Management Controversies and Treatment Strategies for Borderline Resectable
      Pancreatic Cancer.
AB  - The management of borderline resectable cancer requires multi-disciplinary care
      including state-of-the-art radiographic imaging, combination treatment planning
      with medical oncology and radiation oncology, and technical surgical expertise
      combining gastrointestinal and vascular surgery.

PMID- 29206021
TI  - Proving Its Worth. Florida's statewide mobile integrated healthcare program for
      Medicare Advantage patients boasts impressive results.

PMID- 29206022
TI  - Pathologic Features of Primary Pancreatic Malignancies.
AB  - This chapter explores the pathologic features of benign and malignant lesions of
      the pancreas. As pathologic classifications evolve, particularly for cystic
      lesions and neuroendocrine tumors, it is important for physicians who treat
      patients with pancreatic neoplasms to fully evaluate these pathologic
      classifications.

PMID- 29206023
TI  - Efficient Gene Delivery Mediated by a Helical Polypeptide: Controlling the
      Membrane Activity via Multivalency and Light-Assisted Photochemical
      Internalization (PCI).
AB  - The development of robust and nontoxic membrane-penetrating materials is highly
      demanded for nonviral gene delivery. Herein, a photosensitizer (PS)-embedded,
      star-shaped helical polypeptide was developed, which combines the advantages of
      multivalency-enhanced intracellular DNA uptake and light-strengthened endosomal
      escape to enable highly efficient gene delivery with low toxicity. 5,10,15,20
      Tetrakis-(4-aminophenyl) porphyrin as a selected PS initiated ring-opening
      polymerization of N-carboxyanhydride and yielded a star-shaped helical
      polypeptide after side-chain functionalization with guanidine groups. The star
      polypeptide afforded a notably higher transfection efficiency and lower
      cytotoxicity than those of its linear analogue. Light irradiation caused almost
      complete (~90%) endosomal release of the DNA cargo via the photochemical
      internalization (PCI) mechanism and further led to a 6-8-fold increment of the
      transfection efficiency in HeLa, B16F10, and RAW 264.7 cells, outperforming
      commercial reagent 25k PEI by up to 3 orders of magnitude. Because the PS and DNA
      cargoes were compartmentalized distantly in the core and polypeptide layers,
      respectively, the generated reactive oxygen species caused minimal damage to DNA
      molecules to preserve their transfection potency. Such multivalency- and PCI
      potentiated gene delivery efficiency was also demonstrated in vivo in melanoma
      bearing mice. This study thus provides a promising strategy to overcome the
      multiple membrane barriers against nonviral gene delivery.

PMID- 29206024
TI  - Toxicity of a Quinaldine-Based Liquid Organic Hydrogen Carrier (LOHC) System
      toward Soil Organisms Arthrobacter globiformis and Folsomia candida.
AB  - The study aims to establish a preliminary environmental assessment of a
      quinaldine-based LOHC system composed of hydrogen-lean, partially hydrogenated,
      and fully hydrogenated forms. We examined their toxicity toward the soil bacteria
      Arthrobacter globiformis and the Collembola Folsomia candida in two exposure
      scenarios, with and without soil, to address differences in the bioavailability
      of the compounds. In both scenarios, no or only slight toxicity toward soil
      bacteria was observed at the highest test concentration (EC50 > 3397 MUmol L-1
      and >4892 MUmol kg-1 dry weight soil). The effects of the three quinaldines on F.
      candida in soil were similar, with EC50 values ranging from 2119 to 2559 MUmol kg
      1 dry weight soil based on nominal concentrations. Additionally, corrected pore
      water-concentration-based EC50 values were calculated by equilibrium partitioning
      using soil/pore-water distribution coefficients. The tests without soil
      (simulating pore-water exposure) revealed higher toxicity, with LC50 values
      between 78.3 and 161.6 MUmol L-1 and deformation of the protective cuticle. These
      results assign the compounds to the category "harmful to soil organisms".
      Potential risks toward the soil environment of the test compounds are discussed
      on the basis of predicted no-effect concentrations.

PMID- 29206025
TI  - Probing Spin Crossover in a Solution by Paramagnetic NMR Spectroscopy.
AB  - Spin transitions in spin-crossover compounds are now routinely studied in the
      solid state by magnetometry; however, only a few methods exist for studies in
      solution. The currently used Evans method, which relies on NMR spectroscopy to
      measure the magnetic susceptibility, requires the availability of a very pure
      sample of the paramagnetic compound and its exact concentration. To overcome
      these limitations, we propose an alternative NMR-based technique for evaluating
      spin-state populations by only using the chemical shifts of a spin-crossover
      compound; those can be routinely obtained for a solution that contains unknown
      impurities and paramagnetic admixtures or is contaminated otherwise.

PMID- 29206026
TI  - Molecular and Ionic Dipole Effects on the Electronic Properties of Si-/SiO2
      Grafted Alkylamine Monolayers.
AB  - In this work, we demonstrate the tunability of electronic properties of Si/SiO2
      substrates by molecular and ionic surface modifications. The changes in the
      electronic properties such as the work function (WF) and electron affinity were
      experimentally measured by the contact potential difference technique and
      theoretically supported by density functional theory calculations. We attribute
      these molecular electronic effects mainly to the variations of molecular and
      surface dipoles of the ionic and neutral species. We have previously shown that
      for the alkylhalide monolayers, changing the tail group from Cl to I decreased
      the WF of the substrate. Here, we report on the opposite trend of WF changes,
      that is, the increase of the WF, obtained by using the anions of these halides
      from Cl- to I-. This trend was observed on self-assembled alkylammonium halide (
      NH3+ X-, where X- = Cl-, Br-, or I-) monolayer-modified substrates. The
      monolayer's formation was supported by ellipsometry measurements, X-ray
      photoelectron spectroscopy, and atomic force microscopy. Comparison of the
      theoretical and experimental data suggests that the ionic surface dipole depends
      mainly on the polarizability and the position of the counter halide anion along
      with the organization and packaging of the layer. The described ionic
      modification can be easily used for facile tailoring and design of the electronic
      properties Si/SiO2 substrates for various device applications.

PMID- 29206027
TI  - Impact of Acceptor Fluorination on the Performance of All-Polymer Solar Cells.
AB  - Here, we systematically study the effect of fluorination on the performance of
      all-polymer solar cells by employing a naphthalene diimide (NDI)-based polymer
      acceptor with thiophene-flanked phenyl co-monomer. Fluorination of the phenyl co
      monomer with either two or four fluorine units is used to create a series of
      acceptor polymers with either no fluorination (PNDITPhT), bifluorination
      (PNDITF2T), or tetrafluorination (PNDITF4T). In blends with the donor polymer
      PTB7-Th, fluorination results in an increase in power conversion efficiency from
      3.1 to 4.6% despite a decrease in open-circuit voltage from 0.86 V
      (unfluorinated) to 0.78 V (tetrafluorinated). Countering this decrease in open
      circuit voltage is an increase in short-circuit current from 7.7 to 11.7 mA/cm2
      as well as an increase in fill factor from 0.45 to 0.53. The origin of the
      improvement in performance with fluorination is explored using a combination of
      morphological, photophysical, and charge-transport studies. Interestingly,
      fluorination is found not to affect the ultrafast charge-generation kinetics, but
      instead is found to improve charge-collection yield subsequent to charge
      generation, linked to improved electron mobility and improved phase separation.
      Fluorination also leads to improved light absorption, with the blue-shifted
      absorption profile of the fluorinated polymers complementing the absorption
      profile of the low-band gap PTB7-Th.

PMID- 29206028
TI  - Direct Electrical Detection of Iodine Gas by a Novel Metal-Organic-Framework
      Based Sensor.
AB  - High-fidelity detection of iodine species is of utmost importance to the safety
      of the population in cases of nuclear accidents or advanced nuclear fuel
      reprocessing. Herein, we describe the success at using impedance spectroscopy to
      directly detect the real-time adsorption of I2 by a metal-organic framework
      zeolitic imidazolate framework (ZIF)-8-based sensor. Methanolic suspensions of
      ZIF-8 were dropcast onto platinum interdigitated electrodes, dried, and exposed
      to gaseous I2 at 25, 40, or 70  degrees C. Using an unoptimized sensor geometry,
      I2 was readily detected at 25  degrees C in air within 720 s of exposure. The
      specific response is attributed to the chemical selectivity of the ZIF-8 toward
      I2. Furthermore, equivalent circuit modeling of the impedance data indicates a
      >105* decrease in ZIF-8 resistance when 116 wt % I2 is adsorbed by ZIF-8 at 70 
      degrees C in air. This irreversible decrease in resistance is accompanied by an
      irreversible loss in the long-range crystallinity, as evidenced by X-ray
      diffraction and infrared spectroscopy. Air, argon, methanol, and water were found
      to produce minimal changes in ZIF-8 impedance. This report demonstrates how
      selective I2 adsorption by ZIF-8 can be leveraged to create a highly selective
      sensor using >105* changes in impedance response to enable the direct electrical
      detection of environmentally relevant gaseous toxins.

PMID- 29206029
TI  - Facile Access to Azafullerenyl Cation C59N+ and Specific Interaction with
      Entrapped Molecules.
AB  - The facile preparation of azafullerenyl cation C59N+ has been achieved by the
      assistance of trifluoromethanesulfonic acid. The thus formed C59N+ was quite
      stable in solution over 1 month and can be used as an intermediate for the
      electrophilic reaction. Applying this method to endohedral azafullerenes,
      corresponding cations (H2@C59N+ and H2O@C59N+) were prepared and the dynamic
      behavior of entrapped molecules was studied on the basis of 1H NMR relaxation
      time measurements. The results indicated that there is strong intramolecular
      C59N+...Odelta-H2 interaction in H2O@C59N+, which stands in contrast to
      isoelectronic H2O@C60 with no electrostatic interaction. We also demonstrated
      that the magnetic shielding environment inside the C59N+ cage closely resembles
      that for isoelectronic C60.

PMID- 29206030
TI  - A Decade of the Protein Corona.
AB  - In this Perspective, we reflect on a decade of research on the protein corona and
      contemplate its broad implications for future science and engineering at the bio
      nano interface. Specifically, we focus on the physical origins and time evolution
      of the protein corona, differences in the nanoparticle-protein entity in in vitro
      and in vivo environments, the role of stealth polymers to minimize the formation
      of the protein corona, relevant computational and theoretical developments, and
      the "biocorona", a concept extrapolated from the field of nanomedicine. We
      conclude the Perspective by outlining future directions and opportunities
      concerning the protein corona in the coming decade.

PMID- 29206031
TI  - Chemoselective Installation of Amine Bonds on Proteins through Aza-Michael
      Ligation.
AB  - Chemical modification of proteins is essential for a variety of important
      diagnostic and therapeutic applications. Many strategies developed to date lack
      chemo- and regioselectivity as well as result in non-native linkages that may
      suffer from instability in vivo and adversely affect the protein's structure and
      function. We describe here the reaction of N-nucleophiles with the amino acid
      dehydroalanine (Dha) in a protein context. When Dha is chemically installed in
      proteins, the addition of a wide-range N-nucleophiles enables the rapid formation
      of amine linkages (secondary and tertiary) in a chemoselective manner under mild,
      biocompatible conditions. These new linkages are stable at a wide range of pH
      values (pH 2.8 to 12.8), under reducing conditions (biological thiols such as
      glutathione) and in human plasma. This method is demonstrated for three proteins
      and is shown to be fully compatible with disulfide bridges, as evidenced by the
      selective modification of recombinant albumin that displays 17 structurally
      relevant disulfides. The practicability and utility of our approach is further
      demonstrated by the construction of a chemically modified C2A domain of
      Synaptotagmin-I protein that retains its ability to preferentially bind to
      apoptotic cells at a level comparable to the native protein. Importantly, the
      method was useful for building a homogeneous antibody-drug conjugate with a
      precise drug-to-antibody ratio of 2. The kinase inhibitor crizotinib was directly
      conjugated to Dha through its piperidine motif, and its antibody-mediated
      intracellular delivery results in 10-fold improvement of its cancer cell-killing
      efficacy. The simplicity and exquisite site-selectivity of the aza-Michael
      ligation described herein allows the construction of stable secondary and
      tertiary amine-linked protein conjugates without affecting the structure and
      function of biologically relevant proteins.

PMID- 29206033
TI  - Aromaticity-Driven Molecular Structural Variation and Electronic Configuration
      Alternation: An Example of Cyclic pi Conjugation Involving a Mo-Mo delta Bond.
AB  - We have synthesized and characterized the mixed-ligand dimolybdenum paddlewheel
      complex Na[(DAniF)3Mo2(C3S5)] (Na[1]; DAniF = N,N'-di-p-anisylformamidinate, dmit
      = 1,3-dithiole-2-thione-4,5-dithiolate), which has a six-membered chelating
      [Mo2S2C2] ring created by equatorial coordination of the dmit (C3S5) ligand to
      the Mo2 unit. One-electron oxidation of Na[1] using Cp2FePF6 yields the neutral
      complex [(DAniF)3Mo2(C3S5)] ([1]), and removal of two electrons from Na[1] using
      AgBPh4 gives [(DAniF)3Mo2(C3S5)]BPh4 ([1]BPh4). In the crystal structures, [1]-
      and [1] present dihedral angles of 118.9 and 142.3 degrees  between the plane
      defined by the Mo-Mo bond vector and the dmit ligand, respectively, while DFT
      calculations show that in [1]+ the Mo-Mo bond and the dmit ligand are coplanar.
      Complex [1] is paramagnetic with a g value of 1.961 in the EPR spectrum and has a
      Mo-Mo bond distance of 2.133(1) A, increased from 2.0963(9) A for [1]-.
      Consistently, a broad absorption band is observed for [1] in the near-IR region,
      which arises from charge transfer from the dmit ligand to the cationic Mo25+
      centers. Interestingly, complex [1]+ has an aromatic [Mo2S2C2] core, as evidenced
      by a large diamagnetic anisotropy, in addition to the coplanarity of the core
      structure, which shifts downfield the 1H NMR signal of the horizontal methine
      proton (ArN-(CH)-NAr) but upfield those of the vertical protons, relative to the
      methine proton resonances for the precursor ([1]-). The magnetic anisotropy
      (Deltachi = chi? - chi?) for the [Mo2S2C2] ring in [1]+ is -105.5 ppm cgs,
      calculated from the McConnell equation, which is about 2-fold larger than that
      for benzene. The aromaticity of the [Mo2S2C2] ring is supported by theoretical
      studies, including single-point calculations and gauge-including atomic orbital
      (GIAO) NMR spectroscopic calculations at the density functional theory (DFT)
      level. DFT calculations also show that the [Mo2S2C2] core in [1]+ possesses a set
      of three highest occupied and three lowest unoccupied molecular orbitals in pi
      character, corresponding to those of benzene in symmetry, and six pi electrons
      that conform to the Huckel 4n + 2 rule for aromaticity. Therefore, this study
      shows that an aromatic [Mo2S2C2] core is formed by coupling the delta orbital of
      the Mo?Mo bond with the pi orbital of the C?C bond through the bridging atoms
      (S), thus validating the equivalency in bonding functionality between delta and
      pi orbitals.

PMID- 29206032
TI  - Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti
      Amoebic Drugs against Naegleria fowleri.
AB  - The overall aim of this study was to determine whether conjugation with silver
      nanoparticles enhances effects of available drugs against primary amoebic
      meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and
      Fluconazole were conjugated with silver nanoparticles, and synthesis was
      confirmed using UV-visible spectrophotometry. Atomic force microscopy determined
      their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri
      were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles
      alone, and drugs alone. The findings revealed that silver nanoparticles
      conjugation significantly enhanced antiamoebic effects of Nystatin and
      Amphotericin B but not Fluconazole at micromolar concentrations, compared with
      the drugs alone. For the first time, our findings showed that silver nanoparticle
      conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the
      rarity of the disease and challenges in developing new drugs, it is hoped that
      modifying existing drugs to enhance their antiamoebic effects is a useful avenue
      that holds promise in improving the treatment of brain-eating amoebae infection
      due to N. fowleri.

PMID- 29206034
TI  - Self-Assembly of a Tetraphenylethylene-Based Capsule Showing Both Aggregation-
      and Encapsulation-Induced Emission Properties.
AB  - Functional molecular capsules have attracted a lot of attention in recent years
      because of their potential applications as chemosensors, catalysis, drug
      carriers, and so on. We report here the coordination-directed self-assembly of a
      fluorescent-lantern-type molecular capsule from four tetraphenylethylene-based
      ditopic ligands and two square-planar palladium(II) ions. The capsule has been
      thoroughly characterized by UV-vis, 1D/2D NMR, electrospray ionization time-of
      flight mass spectrometry, and single-crystal X-ray diffraction studies. The
      aggregation-induced emission performance of the capsule has been studied by
      tuning the ratio of mixed solvents. Moreover, with an open cavity, the
      fluorescence of the capsule also displays anion sensitivity, with the best turn
      on responsiveness observed for HCO3-, demonstrating for the first time an
      encapsulation-induced emission property.

PMID- 29206035
TI  - Stable Carbocation Generated via 2,5-Cyclohexadien-1-one Protonation.
AB  - Protonation of a substituted cyclohexadien-1-one (1) leads to the generation of
      carbocation [3]+, capable of effecting hydride abstraction and oxidation
      reactions. The molecular structure of [3]+ shows it to be structurally similar to
      [(p-MeO-C6H4)Ph2C]+. The ability to easily access [3]+ from stable and available
      precursors, such as 1 and commercially available acids, may allow a wider
      application of the growing number of trityl-based reactions in organic syntheses.

PMID- 29206036
TI  - The Design and Development of a Potent and Selective Novel Diprolyl Derivative
      That Binds to the N-Domain of Angiotensin-I Converting Enzyme.
AB  - Angiotensin-I converting enzyme (ACE) is a zinc metalloprotease consisting of two
      catalytic domains (N- and C-). Most clinical ACE inhibitor(s) (ACEi) have been
      shown to inhibit both domains nonselectively, resulting in adverse effects such
      as cough and angioedema. Selectively inhibiting the individual domains is likely
      to reduce these effects and potentially treat fibrosis in addition to
      hypertension. ACEi from the GVK Biosciences database were inspected for possible
      N-domain selective binding patterns. From this set, a diprolyl chemical series
      was modeled using docking simulations. The series was expanded based on key
      target interactions involving residues known to impart N-domain selectivity. In
      total, seven diprolyl compounds were synthesized and tested for N-domain
      selective ACE inhibition. One compound with an aspartic acid in the P2 position
      (compound 16) displayed potent inhibition (Ki = 11.45 nM) and was 84-fold more
      selective toward the N-domain. A high-resolution crystal structure of compound 16
      in complex with the N-domain revealed the molecular basis for the observed
      selectivity.

PMID- 29206037
TI  - Macroamidine Formation in Bottromycins Is Catalyzed by a Divergent YcaO Enzyme.
AB  - The YcaO superfamily of proteins catalyzes the phosphorylation of peptide
      backbone amide bonds, which leads to the formation of azolines and azoles in
      ribosomally synthesized and post-translationally modified peptides (RiPPs).
      Bottromycins are RiPPs with potent antimicrobial activity, and their biosynthetic
      pathway contains two divergent, stand-alone YcaO enzymes, IpoC and PurCD. From an
      untargeted metabolomics approach, it had been suggested that PurCD acts with a
      partner protein to form the 12-membered macroamidine unique to bottromycins. Here
      we report the biochemical characterization of IpoC and PurCD. We demonstrate that
      IpoC installs a cysteine-derived thiazoline, whereas PurCD alone is sufficient to
      create the macroamidine structure. Both enzymes are catalytically promiscuous,
      and we generated 10 different macroamidines. Our data provide important insights
      into the versatility of YcaO enzymes, their ability to utilize different
      nucleophiles and provide a framework for the creation of novel bottromycin
      derivatives with enhanced bioactivity.

PMID- 29206038
TI  - Introducing the Bipolar Solvent Media Using the Aqueous Mixtures of Amino Acid
      Anion-Based Ionic Liquids.
AB  - To carry out a chemical reaction between the reactants with largely different
      polarities, it becomes important to have a reaction medium that possesses both
      the polar and nonpolar solvation environments. In an attempt to explore the
      reaction media with such unique polarity properties, the present study provides a
      thorough understanding of the bipolar solvent media using the aqueous mixtures of
      amino acid anion-based ionic liquids. The highly polar behavior of the binary
      mixtures used in the study has been ascribed to the pure ionic liquid state.
      However, the less polar solvation shells have been attributed to the presence of
      a neutral form of the anions. Addition of water in the amino acid anion-based
      ionic liquids causes the protonation of a certain fraction of the anions of the
      ionic liquids, resulting into the formation of a less polar nonionic protonated
      form along with the highly polar natural anionic form. This results into the
      formation of two solvation spheres with different polarities, which can be seen
      very clearly from the presence of two absorption bands (lower wavelength
      absorption band and higher wavelength absorption band) in the UV-vis absorption
      spectrum of Reichardt's ET(30) dye and two emission bands (lower wavelength
      emission band and higher wavelength emission band) in the fluorescence emission
      spectrum of C481 dye. The values of the ETN polarity parameter corresponding to
      the two solvation shells having different polarities have been calculated from
      the deconvoluted absorption spectra of the Reichardt's ET(30) and were analyzed
      in three amino acid anion-based ionic liquids. Generation of the neutral form of
      anions in the aqueous mixtures formed via a protonation transfer reaction has
      been confirmed by the 1H NMR spectroscopy and UV-vis absorption spectrum of
      18DHAQ dye. The study also establishes that the Reichardt's ET(30) dye can be
      used as a valid polarity probe to study the solvatochromic behavior of the binary
      mixtures of amino acid-based ionic liquids.

PMID- 29206039
TI  - Theoretical Insights on the Inefficiency of RNA Oxidative Damage under Aerobic
      Conditions.
AB  - Oxidative damage to RNA has been linked to change or loss of RNA function and
      development of many human age-related diseases. However, knowledge on the nature
      of RNA oxidative damage is relatively limited. In this study, oxidative damage to
      RNA is investigated under anaerobic and aerobic conditions by exploring the
      properties and reactions of 5-hydroxyl-2'-uridin-6-yl and its peroxyl
      diastereoisomers in the RNA strand, respectively. Selective addition of OH to the
      nucleic base from the 5'-end is studied at the molecular level for the first
      time, explaining the large number of the 5S-isomer available for further
      reactions. Our results provide clear evidence that the efficiency of C2'-H2' bond
      activation in the peroxyl isomers is lower than in the carbon radical species. An
      exception is observed for the isomer cis-(5S,6R)-A1, whose internucleotidyl H2'
      abstraction barrier is far smaller than that in the corresponding C6-yl radical.
      However, analysis of the equilibrium species distribution reveals that the amount
      of cis-(5S,6R)-A1 is very small among the peroxyl diastereoisomers, and hence the
      resulting products from direct strand scission should be a less important
      component in RNA oxidative damage. The species with maximum distribution is the
      cis-(5S,6R)-B1 isomer, which is derived from cis-(5S,6R)-A1 and has a moderate
      intranucleotidyl H2'-abstraction barrier. More importantly, the reaction is
      mildly exothermic. These results show that the main fraction of the
      intranucleotidyl H2'-abstraction intermediates can be formed from the cis-(5S,6R)
      B1 isomer. The absolute reduction potentials, the hydrogen atom binding energies,
      and the key structural parameters of the C6-peroxyl species are used to
      understand the diverse reactivity of the cis-(5S,6R) diastereoisomers toward the
      C2'-H2' bonds activation. The present study shows that in addition to the
      selectivity of the OH radical addition, there is a strong correlation between the
      conformation of the modified uracil base and its reactivity in RNA oxidative
      damage.

PMID- 29206040
TI  - Influence of the Location of Attractive Polymer-Pore Interactions on
      Translocation Dynamics.
AB  - We probe the influence of polymer-pore interactions on the translocation dynamics
      using Langevin dynamics simulations. We investigate the effect of the strength
      and location of the polymer-pore interaction using nanopores that are partially
      charged either at the entry or the exit or on both sides of the pore. We study
      the change in the translocation time as a function of the strength of the polymer
      pore interaction for a given chain length and under the effect of an externally
      applied field. Under a moderate driving force and a chain length longer than the
      length of the pore, the translocation time shows a nonmonotonic increase with an
      increase in the attractive interaction. Also, an interaction on the cis side of
      the pore can increase the translocation probability. In the presence of an
      external field and a strong attractive force, the translocation time for shorter
      chains is independent of the polymer-pore interaction at the entry side of the
      pore, whereas an interaction on the trans side dominates the translocation
      process. Our simulation results are rationalized by a qualitative analysis of the
      free energy landscape for polymer translocation.

PMID- 29206042
TI  - Chemoselective Deprotection of Sulfonamides Under Acidic Conditions: Scope,
      Sulfonyl Group Migration, and Synthetic Applications.
AB  - Chemoselective acidic hydrolysis of sulfonamides with trifluoromethanesulfonic
      acid has been evaluated as a deprotection method and further extended to more
      complex synthetic applications. In contrast to conventional troublesome
      sulfonamide hydrolysis, a near-stoichiometric amount of acid was found to be
      sufficient to bring about efficient deprotection of various neutral or electron
      deficient N-arylsulfonamides, whereas electron-rich substrates provided sulfonyl
      group migration products. The deprotection method developed is fully selective
      for N-arylsulfonamides, and the possibility to discriminate among various
      different sulfonamides is demonstrated.

PMID- 29206041
TI  - Lipidated Peptide Dendrimers Killing Multidrug-Resistant Bacteria.
AB  - New antibiotics are urgently needed to address multidrug-resistant (MDR)
      bacteria. Herein we report that second-generation (G2) peptide dendrimers bearing
      a fatty acid chain at the dendrimer core efficiently kill Gram-negative bacteria
      including Pseudomonas aeruginosa and Acinetobacter baumannii, two of the most
      problematic MDR bacteria worldwide. Our most active dendrimer TNS18 is also
      active against Gram-positive methicillin-resistant Staphylococcus aureus. Based
      on circular dichroism and molecular dynamics studies, we hypothesize that TNS18
      adopts a hydrophobically collapsed conformation in water with the fatty acid
      chain backfolded onto the peptide dendrimer branches and that the dendrimer
      unfolds in contact with the membrane to expose its lipid chain and hydrophobic
      residues, thereby facilitating membrane disruption leading to rapid bacterial
      cell death. Dendrimer TNS18 shows promising in vivo activity against MDR clinical
      isolates of A. baumannii and Escherichia coli, suggesting that lipidated peptide
      dendrimers might become a new class of antibacterial agents.

PMID- 29206043
TI  - High-Throughput Computational Screening of Multivariate Metal-Organic Frameworks
      (MTV-MOFs) for CO2 Capture.
AB  - Multivariate metal-organic frameworks (MTV-MOFs) contain multiple linker types
      within a single structure. Arrangements of linkers containing different
      functional groups confer structural diversity and surface heterogeneity and
      result in a combinatorial explosion in the number of possible structures. In this
      work, we carried out high-throughput computational screening of a large number of
      computer-generated MTV-MOFs to assess their CO2 capture properties using grand
      canonical Monte Carlo simulations. The results demonstrate that functionalization
      enhances CO2 capture performance of MTV-MOFs when compared to their parent
      (unfunctionalized) counterparts, and the pore size plays a dominant role in
      determining the CO2 adsorption capabilities of MTV-MOFs irrespective of the
      combinations of the three functional groups (-F, -NH2, and -OCH3) that we
      investigated. We also found that the functionalization of parent MOFs with small
      pores led to larger enhancements in CO2 uptake and CO2/N2 selectivity than
      functionalization in larger-pore MOFs. Free energy contour maps are presented to
      visually compare the influence of linker functionalization between frameworks
      with large and small pores.

PMID- 29206044
TI  - Bicyclization of Azomethine Ylide: Access to Highly Functionalized 3H-Pyrrolo[2,3
      c]quinolines.
AB  - A tandem bicyclization of azomethine ylides with methyleneaminochalcones was
      developed for the straightforward and facile synthesis of 2-substituted
      polyfunctionalized pyrrolo[2,3-c]quinolines. Both an unusual reactivity profile
      of azomethine ylide and a novel strategy for the construction of the tricyclic
      framework by the successive construction of the pyridine and pyrrole rings were
      exhibited in this domino reaction. Two intermediates are isolated in the control
      experiments, and thus a tandem bicyclization/elimination/oxidative aromatization
      process is proposed for the reaction mechanism.

PMID- 29206045
TI  - Reversible and Continuously Tunable Control of Charge of Close Surfaces.
AB  - Surfaces of almost all types of materials are often charged easily by contact
      electrification or deposition of ions; hence, surface charge is ubiquitous and
      has a vast range of influences in our lives and in industry. Since the 19th
      century, scientists have been measuring the charge of multiple materials
      collectively. The common expectation is that the total charge of multiple
      materials is equal to the sum of the charges of the individual materials. This
      study describes a previously unreported phenomenon in which the total charge of
      two insulating surfaces decreases when the surfaces are brought close to each
      other. The charge varies continuously and reversibly depending on the distance of
      separation between the surfaces. Experimental results derived from analyzing the
      movement of charge suggest that the changes are due to a rapid exchange of charge
      between the surfaces and their surrounding air. This change can be used to
      control the surface charge of the materials flexibly and reversibly.

PMID- 29206046
TI  - Hydrophobic Ion Pairing of Peptide Antibiotics for Processing into Controlled
      Release Nanocarrier Formulations.
AB  - Nanoprecipitation of active pharmaceutical ingredients (APIs) to form
      nanocarriers (NCs) is an attractive method of producing formulations with
      improved stability and biological efficacies. However, nanoprecipitation
      techniques have not been demonstrated for highly soluble peptide therapeutics. We
      here present a model and technique to encapsulate highly water-soluble biologic
      APIs by manipulating API salt forms. APIs are ion paired with hydrophobic
      counterions to produce new API salts that exhibit altered solubilities suitable
      for nanoprecipitation processing. The governing rules of ion pair identity and
      processing conditions required for successful encapsulation are experimentally
      determined and assessed with theoretical models. Successful NC formation for the
      antibiotic polymyxin B requires hydrophobicity of the ion pair acid to be greater
      than logP = 2 for strong acids and greater than logP = 8 for weak acids. Oleic
      acid with a logP = 8, and pKa = 5, appears to be a prime candidate as an ion pair
      agent since it is biocompatible and forms excellent ion pair complexes. NC
      formation from preformed, organic soluble ion pairs is compared to in situ ion
      pairs where NCs are made in a single precipitation step. NC properties, such as
      stability and release rates, can be tuned by varying ion pair molecular structure
      and ion pair-to-API molar ratios. For polymyxin B, NCs ~ 100-200 nm in size,
      displaying API release rates over 3 days, were produced. This work demonstrates a
      new approach that enables the formation of nanoparticles from previously
      intractable compounds.

PMID- 29206047
TI  - Toward Maximizing the Mechanical Property of Interconnected Macroporous
      Polystyrenes Made from High Internal Phase Emulsions.
AB  - Macroporous materials polymerized from high internal phase emulsions (PolyHIPEs)
      possess well-defined interconnected porous structures and tunable device shapes.
      This provides interesting property characteristics well-suited for a variety of
      applications. However, such materials also demonstrate poor mechanical
      performances, which limit their potential use. As will be demonstrated, this
      results from the high surfactant content required by PolyHIPEs. Herein, a new
      approach is introduced for designing a highly efficient polymeric surfactant,
      which generates interconnected pores in PolyHIPEs through designing an
      incompatible surfactant and skeleton material. The surfactant also possesses a
      hyperbranched topology, which combines the strong amphipathy of small molecular
      surfactants and the nanosphere structure of Pickering emulsifiers to provide an
      excellent colloidal stability to HIPEs. A hyperbranched polyethylene having
      pendant sodium sulfonate groups (HBPE-SO3Na) was thus designed and synthesized
      via chain walking copolymerization of ethylene and 2-trimethylsilyloxyethyl
      acrylate followed by sulfonation. Stable HIPEs of styrene/divinylbenzene and
      water at a weight ratio of 1 to 5 were obtained with using HBPE-SO3Na. The
      polymerization of HIPEs produced interconnected macroporous polystyrenes (PSs) at
      a substantially lower surfactant content, for example, 0.5 wt % HBPE-SO3Na. The
      compressive Young's moduli of PolyHIPEs reached 104-111 MPa with 0.5-2 wt % HBPE
      SO3Na, which is the first reported case of a PS-based PolyHIPE achieving its
      theoretical modulus. The PolyHIPE was used to support Au nanoparticles and embed
      in a column for oxidation of dimethylphenylsilane. A complete conversion of
      dimethylphenylsilanol was achieved with low column back pressure in a 50 h
      continuous reaction with no degradation of PolyHIPE integrity and mechanical
      property.

PMID- 29206048
TI  - Orientation Control of Hemispherical Janus Particles and Metal Coating on the
      Selective Surface To Excite Surface Plasmon Polaritons in the Micro-Kretschmann
      Geometry.
AB  - Asymmetric-shaped particles (the Janus particle) are difficult to be arranged in
      a uniform orientation on a solid substrate. This difficulty prevents further
      modification of the selective surface of the particles for fabrication of the
      Janus particles with anisotropy of the shape and surface. We successfully
      arranged hemispherical particles in a uniform orientation at the air-water
      interface. The particles were arranged on the solid substrate in a uniform
      orientation by transferring the particle film onto the substrate. This
      arrangement enabled the fabrication of the Janus particles with anisotropy of the
      shape and surface by selective deposition of a film on either the equatorial
      plane or the spherical surface. Additionally, we demonstrated the function of the
      microscopic Kretschmann geometry for excitation of the surface plasmon polaritons
      of a thin metal film on the equatorial plane of a single hemispherical particle.

PMID- 29206049
TI  - Rationale and design of the 500-patient, 3-year, and prospective Vigilant
      ObservatIon of GlIadeL WAfer ImplaNT registry.
AB  - Implantation of biodegradable wafers impregnated with carmustine (BCNU) is one of
      the few chemotherapeutic modalities that have been evaluated in Phase III trials
      and approved by the US FDA for treatment of newly diagnosed high-grade glioma and
      recurrent glioblastoma. Enrolling up to 500 patients for 3-year follow-up at over
      30 sites, the prospective Vigilant ObservatIon of GlIadeL WAfer ImplaNT
      (VIGILANT) registry (NCT02684838) will evaluate BCNU wafers for treatment of CNS
      malignancies in contemporary practice and in the new era of molecular tumor
      analysis. Subgroup analyses will include tumor type, molecular marker status, and
      treatment combinations. Interim analyses from the VIGILANT registry will be
      reported until complete results are available in 2024.

PMID- 29206050
TI  - Association between short and long sleep durations and cardiovascular outcomes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: A shorter sleep duration has been identified as a risk factor for
      cardiovascular diseases and increased mortality. It has been hypothesized that a
      short sleep duration may be linked to changes in ghrelin and leptin production,
      leading to an alteration of stress hormone production. Here, we conducted a
      systematic review and meta-analysis to investigate the potential relationship
      between a sleep duration and cardiovascular disease mortality. METHODS: We
      conducted a comprehensive search of Ovid Medline In-Process and other non-indexed
      citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of
      Controlled Trials, and Scopus from database inception to March 2017.
      Observational studies were included if the studies reported hazard ratios or odds
      ratios of the associations between sleep durations (short and long) and
      cardiovascular disease mortality. Data were extracted by a reviewer and then
      reviewed by two separate reviewers. Conflicts were resolved through consensus.
      Using the DerSimonian and Laird random effects models, we calculated pooled
      hazard ratios and pooled odds ratios with 95% confidence intervals (CI). Subgroup
      analyses were performed to explore potential sources of heterogeneity. The
      quality of the included studies and publication bias were assessed. RESULTS: In
      total, our meta-analysis included 19 studies (31 cohorts) with a total of 816,995
      individuals with 42,870 cardiovascular disease mortality cases. In pooled
      analyses, both short (risk ratio 1.19; 95% CI 1.13 to 1.26, P<0.001, I2=30.7,
      Pheterogeneity=0.034), and long (risk ratio 1.37; 95% CI 1.23 to 1.52, P<0.001,
      I2=79.75, Pheterogeneity<0.001) sleep durations were associated with a greater
      risk of cardiovascular disease mortality. CONCLUSIONS: Both short (<7 hours) and
      long sleep durations (>9 hours) can increase the risk of overall cardiovascular
      disease mortality, particularly in Asian populations and elderly individuals.
      Future epidemiological studies would ideally include objective sleep
      measurements, rather than self-report measures, and all potential confounders,
      such as genetic variants.

PMID- 29206051
TI  - Superchilling of muscle foods: Potential alternative for chilling and freezing.
AB  - Superchilling is an attractive technique for preservation of muscle foods which
      freezes part of the water and insulate the food products from temperature
      fluctuations thereby enhancing the shelf-life during storage, transportation and
      retailing. Superchilling process synergistically improves the product shelf-life
      when used in combination with vacuum or modified atmospheric packaging. The shelf
      life of muscle foods was reported to be increased by 1.5 to 4.0 times relative to
      traditional chilling technique. Advantages of superchilling and its ability to
      maintain the freshness of muscle foods over freezing has been discussed and its
      potential for Industrial application is highlighted. Present review also unravel
      the mechanistic bases for ice-crystal formation during superchilling and measures
      to ameliorate the drip loss. The future challenges especially automation in
      superchilling process for large scale Industrial application is presented.

PMID- 29206052
TI  - Risk Trajectories of Readmission and Death in the First Year after
      Hospitalization for Chronic Obstructive Pulmonary Disease.
AB  - RATIONALE: Characterization of the dynamic nature of posthospital risk in chronic
      obstructive pulmonary disease (COPD) is needed to provide counseling and plan
      clinical services. OBJECTIVES: To analyze risk of readmission and death after
      discharge for COPD among Medicare beneficiaries aged 65 years and older and to
      determine the association between ventilator support and risk trajectory.
      METHODS: We computed daily absolute risks of hospital readmission and death for 1
      year after discharge for COPD, stratified by ventilator support. We determined
      the time required for risks to decline by 50% from maximum daily values after
      discharge and for daily risks to plateau. We compared risks with those found in
      the general elderly population. MEASUREMENTS AND MAIN RESULTS: Among 2,340,637
      hospitalizations, the readmission rate at 1 year was 64.2%, including 63.5%,
      66.0%, and 64.1% among those receiving invasive, noninvasive, and no ventilation,
      respectively. Among 1,283,069 hospitalizations, mortality at 1 year was 26.2%,
      including 45.7%, 41.8%, and 24.4% among those same respective groups. Daily risk
      of readmission declined by 50% within 28, 39, and 43 days and plateaued at 46,
      54, and 61 days among those receiving invasive, noninvasive, and no ventilation,
      respectively. Risk of death declined by 50% by 3, 4, and 17 days and plateaued by
      21, 18, and 24 days in the same respective groups. Risks of hospitalization and
      death were significantly higher after discharge for COPD than among the general
      Medicare population. CONCLUSIONS: Discharge from the hospital is associated with
      prolonged risks of readmission and death that vary with need for ventilator
      support. Interventions limited to the first month after discharge may be
      insufficient to improve longitudinal outcomes.

PMID- 29206053
TI  - Increasing Physical Activity in Daily Life in Chronic Obstructive Pulmonary
      Disease: To Solve the Puzzle, Every Piece Counts.

PMID- 29206054
TI  - Reply to Rodrigues et al.: Increasing Physical Activity in Daily Life in Chronic
      Obstructive Pulmonary Disease: To Solve the Puzzle, Every Piece Counts.

PMID- 29206055
TI  - Association study of FOXP3 gene and the risk of 0020 pre-eclampsia.
AB  - Pre-eclampsia (PE) is a multifactorial pregnancy disorder, with serious
      consequences for both the mother and the fetus. Despite intense studies, the
      pathophysiology of PE remains enigmatic. Previous studies suggested that Treg
      dysfunction is involved in the pathogenesis of PE. We hypothesized that
      functional variants of the FOXP3 gene might be associated with PE via
      dysregulation of Treg cells. Of the 276 subjects, we genotyped three variants of
      FOXP3 by PCR-RFLP and Tetra ARMS-PCR methods. The genotypic frequencies of
      rs2232365 were found to be protective from the development of PE under codominant
      [odds ratio (OR) 0.49, 95 percent confidence interval (CI) 0.28-0.87, p-value =
      0.043], dominant [odds ratio (OR) 0.54, 95 percent confidence interval (CI) 0.32
      0.94, p-value = 0.027] and over dominant [odds ratio (OR) 0.57, 95 percent
      confidence interval (CI) 0.35-0.92, p-value = 0.02] models. Moreover, the
      rs3761548 conferred a risk of PE in recessive model [odds ratio (OR) 2.05, 95
      percent confidence interval (CI) 1.08-3.88, p-value = 0.025]. However, no
      mutation was detected in FOXP3 exon2 in any of the studied samples. Based on our
      results, thought that FOXP3 variants may be an important contributor for the
      progression of PE in Iranian women.

PMID- 29206056
TI  - Ease of use of two autoinjectors in patients with multiple sclerosis treated with
      interferon beta-1a subcutaneously three times weekly: results of the randomized,
      crossover REDEFINE study.
AB  - BACKGROUND: For interferon beta-1a subcutaneously three times weekly (IFN beta-1a
      SC tiw), administration options include manually injected prefilled syringes; a
      preassembled, single-use autoinjector; and a reusable autoinjector. This study
      evaluated patient-perceived ease of use of two injection devices. RESEARCH DESIGN
      AND METHODS: REDEFINE, a Phase IV, multicenter crossover study, randomized
      patients with multiple sclerosis and >=5 weeks' IFN beta-1a 44 MUg SC tiw use to
      4 weeks using a single-use autoinjector, then 4 weeks using a reusable
      autoinjector, or vice versa. The primary endpoint was the proportion rating each
      'easy' or 'very easy', with/without regard to previous device experience.
      RESULTS: Of 97 randomized patients, 29 had most recent experience with manual
      injection; 23 with single-use autoinjector; and 45 with reusable autoinjector.
      68.4% found using the single-use autoinjector very easy or easy, versus 77.9% for
      the reusable device (difference -9.5%; p = 0.200). 40.0% versus 29.5% found the
      respective devices very easy (difference 10.5%; p = 0.203). CONCLUSIONS: Most
      patients found both autoinjectors easy or very easy to use. Having two viable
      options may help accommodate patient preferences. Ease of administration and
      patient satisfaction relates to adherence; satisfied patients may more likely be
      adherent. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov
      (CT.gov identifier: NCT02019550).

PMID- 29206057
TI  - School nurse asthma program reduces healthcare utilization in children with
      persistent asthma.
AB  - OBJECTIVE: We examined the impact of a novel, school nurse-supervised asthma
      therapy program on healthcare utilization. METHODS: We retrospectively reviewed
      charts of 84 children enrolled in this program in central Massachusetts between
      2012 and 2015. Physicians identified children with persistent asthma and poor
      medication adherence. These children were enrolled in the program to receive
      daily-inhaled corticosteroid at school, supervised by their school nurse, with
      ongoing communication between physician's office and school nurse through the
      school year. This program relied on established family, provider and school
      resources rather than research staff. The primary outcome was change in the
      number of emergency department (ED) visits in the year before and after
      enrollment. Secondary outcomes were hospital admissions, school absences, and
      rescue medication use. RESULTS: The study population was on average 10.5 years
      old, 63% male, 67% Hispanic, 19% black, 14% white with 95% using Medicaid
      insurance. Asthma-related ED visits over a 1-year period decreased 37.5%, from a
      pre-intervention mean of 0.8 visits to a post-intervention mean of 0.3 visits (p
      < 0.001). Asthma-related hospital admissions decreased from a pre-intervention
      mean of 0.3 admissions to post-intervention mean of 0 admissions (p < 0.001).
      Asthma rescue medication refills decreased by 46.3% from the pre- to post
      intervention period (p = <.001). There were also non-significant declines in
      school absences and oral steroid use for children enrolled. CONCLUSIONS: We
      demonstrate a significant reduction in healthcare utilization for children
      enrolled in this unique school nurse-supervised asthma program, which utilizes a
      clinical-school partnership to deliver preventative asthma medication to school
      aged children under sustainable conditions.

PMID- 29206059
TI  - Efficacy of an intervention programme for rehabilitation of awareness of deficit
      after acquired brain injury: A pilot study.
AB  - BACKGROUND: Impaired Awareness of Deficit (AD) is a frequent symptom after
      suffering acquired brain injury (ABI) that severely influences patients' daily
      lives. PRIMARY OBJECTIVE: Pilot study to assess the effectiveness of a structured
      intervention programme which was developed from a biopsychosocial approach, and
      relied on common therapeutic strategies of proven effectiveness. METHODS: We
      assessed the effectiveness of our intervention on a sample of 60 patients with
      ABI, 30 of whom received the specific AD intervention programme, while the other
      30 followed an equivalent rehabilitation approach where they received no specific
      intervention on AD. AD were assessed before and after the specific intervention
      on AD through an ad-hoc designed questionnaire. RESULTS: This study reports that
      patients who received the proposed programme demonstrated significant improvement
      in their level of AD, as compared to the control group. This improvement was
      observable on all the proposed dimensions of awareness. Interestingly, results
      from correlation analysis also showed that patients with lower initial AD were
      those who exhibited a greater degree of improvement following the intervention.
      CONCLUSIONS: This research provides evidence in favour of the effectiveness of
      implementing an intervention programme for AD in the context a global
      rehabilitation process for patients with ABI.

PMID- 29206058
TI  - Resveratrol, human health and winemaking perspectives.
AB  - Resveratrol, (3, 5, 4'-trihydroxystilbene) is a non-flavonoid polyphenol stilbene
      synthesized by plants when damaged by infectious diseases or ionizing radiation.
      Although present in more than seventy plant species, grapes and wine are the
      major dietary contributors of resveratrol, responsible for 98% of the daily
      intake. In 1992, Renaud and De Lorgeril first linked wine polyphenols, including
      resveratrol, to the potential health benefits ascribed to regular and moderate
      wine consumption (the so called "French Paradox"). Since then, resveratrol has
      received increasing scientific interest, leading to research on its biological
      actions, and to a large number of published papers, which have been collected and
      discussed in this review. The relatively low amounts of resveratrol measured in
      wine following moderate consumption, however, may be insufficient to mitigate
      biological damage, such as that due to oxidative stress. On this basis, the
      authors also highlight the importance of viticulture and the winemaking process
      to enhance resveratrol concentrations in wine in order to bolster potential
      health benefits.

PMID- 29206060
TI  - War games: using an online game to teach medical students about survival during
      conflict 'When my survival instincts kick in, what am I truly capable of in times
      of conflict?'

PMID- 29206062
TI  - Discrimination between primary low-grade and high-grade glioma with 11C
      methionine PET: a bivariate diagnostic test accuracy meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis evaluating the diagnostic accuracy of 11C
      methionine (MET) positron emission tomography (PET) to discriminate between
      primary low-grade glioma (LGG) and high-grade glioma (HGG). METHODS: A systematic
      database search was performed by a librarian in relevant databases with the
      latest search on 07 November 2016. Hits were assessed for inclusion independently
      by two authors. Individual patient data on relative MET uptake was extracted on
      patients examined pre-operatively with MET PET and subsequent neuropathological
      diagnosis of astrocytoma or oligodendroglioma. Individual patient data were
      analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta
      analysis model with restricted maximum likelihood estimation method. Bivariate
      meta-regression and subgroup analyses assessed study heterogeneity and validity.
      This study is registered with PROSPERO, number CRD42016050747. RESULTS: Out of
      1828 hits, 13 studies comprising of 241 individuals were included in the
      quantitative and qualitative analysis. MET PET had an area under the bivariate
      summary receiver operating characteristics curve of 0.78 to discriminate between
      LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI)
      (0.66-0.88) and a summary false positive rate of 0.28, 95% CI (0.19-0.38).
      Heterogeneity was described by; bias in patient inclusion, study quality, and
      ratio method. Optimal cutoff for relative MET uptake was 2.21. CONCLUSION: MET
      PET had a moderately high diagnostic accuracy for the discrimination between
      primary LGG and HGG. Advances in knowledge: MET PET can be used as a clinical
      tool for the non-invasive discrimination between LGG and HGG with a moderately
      high accuracy at cut-off 2.21.

PMID- 29206063
TI  - Age discrimination in out-of-hospital cardiac arrest care: a case-control study.
AB  - BACKGROUND: Although some studies have questioned whether cardiopulmonary
      resuscitation (CPR) in older people could be futile, age is not considered an
      essential out-of-hospital cardiac arrest (OHCA) prognostic factor. However, in
      the daily clinical practice of mobile medical teams (MMTs), age seems to be an
      important factor affecting OHCA care. AIMS: The purpose of this study was to
      compare OHCA care and outcomes between young patients (<65 years old) and older
      patients. METHODS: We performed a case-control study based on data extracted from
      the French National Cardiac Arrest (CA) registry. All adult patients with CA
      recorded between July 2011 and May 2014 were included. Each older patient was
      matched on three criteria: sex, initial cardiac rhythm and no-flow duration.
      RESULTS: We studied 4347 pairs. We found significantly less basic life support
      initiation, shorter advanced cardiac life support duration, less MMT automated
      chest compression, less MMT ventilation and less MMT epinephrine injection in the
      older patients. Significant differences were also observed for return of
      spontaneous circulation (odds ratio (OR)=0.84, 95% confidence interval (CI) 0.77
      0.92, p<0.001), transport to hospital (OR=0.58, 95% CI 0.51-0.61, p<0.001), vital
      status at hospital admission (OR=0.55, 95% CI 0.50-0.60, p<0.001) and vital
      status 30 days after CA (OR=0.42, 95% CI 0.35-0.50, p<0.001). CONCLUSION: All
      OHCA guidelines, ethical statements and clinical procedures do not propose age as
      a discrimination criterion in OHCA care. However, in our case-control study, we
      notice a shorter duration and less intensive care among older patients. This
      finding may partly explain the lower survival rate compared with younger people.

PMID- 29206061
TI  - The clinical value of secretin-enhanced MRCP in the functional and morphological
      assessment of pancreatic diseases.
AB  - Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) provides a
      non-invasive way, with which, to evaluate pancreatic duct (PD) anatomy and
      exocrine pancreatic function. S-MRCP can be added to the routine pancreas MR
      examination in equivocal cases. Moreover, it can detect subtle PD involvement,
      allowing diagnosis of early, rather than end-stage, pancreatic diseases. Although
      S-MRCP is a valuable non-invasive diagnostic method, it is only performed in a
      few centres due to relative high cost. Furthermore, less familiarity with its
      indications, the examination technique, and image interpretation also contribute
      to its limited use. Thus, the purpose of this article is to explain secretin's
      mechanism of action, the examination technique, the clinically relevant
      indications, the advantages, and limitations. Finally, we will focus on image
      analysis and its role in achieving an early and accurate diagnosis of specific
      pancreatic and PD diseases.

PMID- 29206064
TI  - Predicting the likelihood of postoperative seizure status based on mRNA
      sequencing in low-grade gliomas.
AB  - AIM: No comprehensive and objective methods yet exist for predicting
      postoperative seizure. PATIENTS & METHODS: mRNA-seq data and corresponding
      postoperative seizure status of 109 low-grade glioma samples were obtained from
      Chinese Glioma Genome Atlas database and divided into two sets randomly. Logistic
      regression and receiver operating characteristic analysis with risk score method
      were used to develop a ten-gene prediction model. RESULTS: Considering gene
      number and area under the curve of receiver operating characteristic, a ten-gene
      model was generated which showed an area under the curve of 0.9965 in training
      set. Patients with high-risk scores had higher probability of postoperative
      seizure compared with those with low-risk scores. CONCLUSION: This is the first
      prediction model for postoperative seizures in gliomas, integrating multiple
      genes. Clinical application may help patients with postoperative seizure control.

PMID- 29206065
TI  - Does HIV Really Augment the Frequency or Mortality Risk of Increased Pulmonary
      Artery Systolic Pressures?

PMID- 29206066
TI  - Magnesium induces preconditioning of the neonatal brain via profound
      mitochondrial protection.
AB  - Magnesium sulphate (MgSO4) given to women in preterm labor reduces cerebral palsy
      in their offspring but the mechanism behind this protection is unclear, limiting
      its effective, safe clinical implementation. Previous studies suggest that MgSO4
      is not neuroprotective if administered during or after the insult, so we
      hypothesised that MgSO4 induces preconditioning in the immature brain. Therefore,
      we administered MgSO4 at various time-points before/after unilateral hypoxia
      ischemia (HI) in seven-day-old rats. We found that MgSO4 treatment administered
      as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury,
      with maximal protection achieved by 1.1 mg/g MgSO4 administered 24 h before HI.
      As serum magnesium levels returned to baseline before the induction of HI, we
      ascribed this reduction in brain injury to preconditioning. Cerebral blood flow
      was unaffected, but mRNAs/miRNAs involved in mitochondrial function and
      metabolism were modulated by MgSO4. Metabolomic analysis (H+-NMR) disclosed that
      MgSO4 attenuated HI-induced increases in succinate and prevented depletion of
      high-energy phosphates. MgSO4 pretreatment preserved mitochondrial respiration,
      reducing ROS production and inflammation after HI. Therefore, we propose that
      MgSO4 evokes preconditioning via induction of mitochondrial resistance and
      attenuation of inflammation.

PMID- 29206067
TI  - Oligomeric and fibrillar amyloid beta 42 induce platelet aggregation partially
      through GPVI.
AB  - The effects of the Alzheimer's disease (AD)-associated Amyloid-beta (Abeta)
      peptides on platelet aggregation have been previously assessed, but most of these
      studies focused on Abeta40 species. It also remains to be determined which
      distinct forms of Abeta peptides exert differential effects on platelets. In AD,
      oligomeric Abeta42 species is widely thought to be a major contributor to the
      disease pathogenesis. We, therefore, examine the ability of oligomeric and
      fibrillary Abeta42 to affect platelet aggregation. We show that both forms of
      Abeta42 induced significant platelet aggregation and that it is a novel ligand
      for the platelet receptor GPVI. Furthermore, a novel binding peptide that reduces
      the formation of soluble Abeta42 oligomers was effective at preventing Abeta42
      dependent platelet aggregation. These results support a role for Abeta42
      oligomers in platelet hyperactivity.

PMID- 29206068
TI  - Is It Safe to Discontinue Statins? Does Stopping Statins Improve Quality of Life:
      Yes and No.

PMID- 29206069
TI  - The Palliative Care Resource Nurses Pilot Survey: A Descriptive Report of Their
      Primary Palliative Care Role and Educational Needs.

PMID- 29206070
TI  - Efficacy of platelet concentrates in bone healing: A systematic review on animal
      studies - Part B: Large-size animal models.
AB  - In the presence of large bone defects, delayed bone union, or nonunion and
      fractures, bone reconstruction may be necessary. Different strategies have been
      employed to enhance bone healing among which the use of autologous platelet
      concentrates (APCs). Due to the high content of platelets and platelet-derived
      bioactive molecules (e.g., growth factors, antimicrobial peptides), they are
      promising candidates to enhance bone healing. However, both preclinical and
      clinical studies produced contrasting results, mainly due to a high heterogeneity
      in study design, objectives, techniques adopted, and outcomes assessed. The aim
      of the present systematic review was to evaluate the efficacy of APCs in animal
      models of bone regeneration, considering the possible factors that might affect
      the outcome. An electronic search was performed on MEDLINE and Scopus databases.
      Comparative animal studies with a minimum follow up of 2 weeks, at least five
      subjects per group and using APCs for regeneration of bone defects were included.
      Articles underwent risk of bias assessment and quality evaluation. Fifty studies
      performed on six animal species (rat, rabbit, dog, sheep, goat, mini-pig) were
      included. The present part of the review considers studies performed on small
      ruminants, dogs, and mini-pigs (14 articles). The majority of the studies were
      considered at low risk of bias. In general, APCs' adjunct positively affected
      bone regeneration. Animal species, platelet and growth factors concentration,
      type of bone defect and of platelet concentrate used seemed to influence their
      efficacy in bone healing. However, sound conclusions were not drawn since too few
      studies for each large-size animal model were included. In addition,
      characterization of APCs' content was performed only in a few studies. Further
      studies with a standardized protocol including characterization of the final
      products will provide useful information for translating the results to clinical
      application of APCs in bone surgery.

PMID- 29206071
TI  - Multivariable analysis of the association between electrolyte disturbances and
      mortality in cats.
AB  - OBJECTIVES: Electrolyte disorders have been individually associated with
      mortality in small populations of cats with specific conditions, but the
      associations and interactions between electrolyte disturbances and outcome have
      not been evaluated in a large, heterogeneous population. It was hypothesized that
      abnormalities of sodium, chloride, potassium and calcium concentrations would be
      independently and proportionately associated with death from natural causes and
      with all-cause mortality in cats. METHODS: An electronic database containing 7064
      electrolyte profiles was constructed to assess the association between disorders
      of sodium, potassium, corrected-chloride and ionized calcium concentrations with
      non-survival by multivariable modelling. A second database containing 2388
      records was used to validate the models constructed from the first database.
      RESULTS: All four electrolytes assessed had non-linear U-shaped associations with
      case fatality rates, wherein concentrations clustered around the reference
      interval had the lowest case fatality rates, while progressively abnormal
      concentrations were associated with proportionately increased risk of non
      survival (area under the receiver operator characteristic curve [AUROC] 0.689) or
      death (AUROC 0.750). CONCLUSIONS AND RELEVANCE: Multivariable modelling suggested
      that these electrolyte disturbances were associated with non-survival and with
      death from natural causes independent of each other. The present study suggests
      that measurement of electrolyte concentrations is an important component of the
      assessment of cats in emergency rooms or intensive care units. Future studies
      should focus on confirming these associations in a prospective manner accounting
      for disease severity.

PMID- 29206072
TI  - Cigarette smoking reduces platelet reactivity independently of clopidogrel
      treatment in patients with non-ST elevation acute coronary syndromes.
AB  - Smokers receiving clopidogrel show a lower residual platelet reactivity than non
      smokers, a phenomenon generally ascribed to smoking-induced increased production
      of clopidogrel active metabolite, but also associated with the high hemoglobin
      levels of smokers, which decreases platelet reactivity in tests that measure
      platelet function in whole blood. We evaluated the impact of cigarette smoking
      and of hemoglobin levels on platelet reactivity index (PRI) measured by the
      vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole
      blood samples from patients with non-ST elevation acute coronary syndrome (NSTE
      ACS) undergoing percutaneous coronary interventions, both before and after
      clopidogrel administration. PRI was measured in 718 clopidogrel-naive NSTE-ACS
      patients, both before and 1 month after treatment with clopidogrel (75 mg daily).
      Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline
      (57.7 +/- 24.1 vs. 64.8 +/- 19.8, p < 0.001) and 1 month (43.4 +/- 20.3% vs. 46.8
      +/- 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders
      (age, sex, diabetes, chronic kidney disease, Syntax score>15), the beta
      coefficient of smoke on PRI was -8.51 [-11.90 to -5.11, p < 0.001] at baseline
      and -3.41 [-6.30 to -0.51, p = 0.02] after 1 month. Hemoglobin was higher in
      smokers (13.8 +/- 1.5 g/dL) than non-smokers (13.1 +/- 1.7 g/dL, p < 0.001), but
      was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60)
      and at 1 month (Rho = 0.01, p = 0.80). Our analysis confirms that clopidogrel
      treated smokers have lower platelet reactivity, measured by the VASP-P assay,
      compared to clopidogrel-treated non-smokers. However, smokers had lower platelet
      reactivity already before receiving clopidogrel treatment, suggesting that smoke
      affects platelet reactivity independently of its potential effect on the
      pharmacokinetics of clopidogrel. Our data also indicate that such an effect is
      not mediated by increased hemoglobin levels.

PMID- 29206073
TI  - Pilot Study: The Effectiveness of Complex Decongestive Therapy for Lymphedema in
      Palliative Care Patients with Advanced Cancer.
AB  - BACKGROUND: Complex decongestive therapy (CDT) is a regimen of physical treatment
      for lymphedema. Its effectiveness is unknown in advanced cancer patients. This
      study evaluates effectiveness of CDT in this population. METHOD: This is a
      prospective observational cohort study for 18 months of advanced cancer patients
      with lymphedema, who received three or more CDT interventions. Measurements were
      taken before the first (T1), third (T3), and sixth (T6) treatments as follows:
      limb volume using circumferential measurements, quality of life (QOL) using
      qualitative questions, skin quality using a locally developed scale measuring
      color, thickness, and texture. The treating physiotherapists collected data.
      Analysis was carried out using Microsoft Excel and SPSS. RESULTS: Twelve
      patients, age range 42-73 years (median 69.5) were included. Survival from last
      recorded treatment ranged from 3 to 262 days (median 40). At T3 (n = 21 limbs),
      volume reduction was significant (Wilcoxin Signed Rank Test Z = -2.5, p = 0.01, r
      = 0.5). At T6 (n = 13 limbs), volume reduction was significant (Z = -2.4, p =
      0.013, r = 0.66). At both time points, there were significant reductions in
      abnormal skin thickness and surface, but not color. Improvements occurred
      independent of volume changes. QOL changes included better function, improved
      limb aesthetics, and less pain and tightness. CONCLUSION: For the first time,
      this study shows that CDT is effective for a cohort of palliative cancer patients
      with limited survival. Improvements in limb volume, skin quality, and lymphedema
      related QOL were recorded. Valid skin and QOL measures need to be developed.
      Larger, blinded trials need to be conducted to determine which patients benefit
      from CDT.

PMID- 29206074
TI  - A novel flow cytometry assay using dihydroethidium as redox-sensitive probe
      reveals NADPH oxidase-dependent generation of superoxide anion in human platelets
      exposed to amyloid peptide beta.
AB  - Reactive oxygen species (ROS) generation is critical in the regulation of
      platelets, which has important implications in the modulation of hemostasis and
      thrombosis. Nonetheless, despite several assays have been described and
      successfully utilized in the past, the analysis of ROS generation in human
      platelets remains challenging. Here we show that dihydroethidium (DHE) allows the
      characterization of redox responses upon platelet activation by physiological and
      pathological stimuli. In particular, the flow cytometry assay that we describe
      here allowed us to confirm that thrombin, collagen-related peptide (CRP) and
      arachidonic acid but not adenosine diphosphate (ADP) stimulate superoxide anion
      formation in a concentration-dependent manner. 0.1unit/ml thrombin, 3 MUg/ml CRP
      and 30 MUM arachidonic acid are commonly used to stimulate platelets in vitro and
      here were shown to stimulate a significant increase in superoxide anion
      formation. The ROS scavenger N-acetylcysteine (NAC) abolished superoxide anion
      generation in response to all tested stimuli, but the pan-NADPH oxidase (NOX)
      inhibitor VAS2870 only inhibited superoxide anion formation in response to
      thrombin and CRP. The involvement of NOXs in thrombin and CRP-dependent responses
      was confirmed by the inhibition of platelet aggregation induced by these stimuli
      by VAS2870, while platelet aggregation in response to arachidonic acid was
      insensitive to this inhibitor. In addition, the pathological platelet stimulus
      amyloid beta (Abeta) 1-42 peptide induced superoxide anion formation in a
      concentration-dependent manner. Abeta peptide stimulated superoxide anion
      formation in a NOX-dependent manner, as proved by the use of VAS2870. Abeta 1-42
      peptide displayed only moderate activity as an aggregation stimulus, but was able
      to significantly potentiate platelet aggregation in response to submaximal
      agonists concentrations, such as 0.03 unit/ml thrombin and 10 MUM arachidonic
      acid. The inhibition of NOXs by 10 MUM VAS2870 abolished Abeta-dependent
      potentiation of platelet aggregation in response to 10 MUM arachidonic acid,
      suggesting that the pro-thrombotic activity of Abeta peptides depends on NOX
      activity. Similar experiments could not be performed with thrombin or collagen,
      as NOXs are required for the signaling induced by these stimuli. These findings
      shed some new light on the pro-thrombotic activity of Abeta peptides. In summary,
      here we describe a novel and reliable assay for the detection of superoxide anion
      in human platelets. This is particularly important for the investigation of the
      pathophysiological role of redox stress in platelets, a field of research of
      increasing importance, but hindered by the absence of a reliable and easily
      accessible ROS detection methodology applicable to platelets.

PMID- 29206075
TI  - Effect of wastewater quality parameters on coliform inactivation by tin oxide
      anodes.
AB  - The effect of six water quality constituents on wastewater effluent disinfection
      by tin oxide anodes (TOAs) was investigated in single cell laboratory reactors.
      Several concentrations of suspended solids, chemical oxygen demand (COD),
      alkalinity, ammonia-nitrogen, nitrite-nitrogen, and nitrate-nitrogen were added
      to media containing 106 total coliform bacteria mL-1. Current was applied through
      the TOAs, and coliform bacteria viability was analyzed over time. Over 99.9%
      inactivation of coliform bacteria was found over 15 min in TOA reactors.
      Concentrations of the six water quality constituents typical of concentrations
      found in wastewaters had no effect on TOA disinfection efficacy. The results of
      this research demonstrate that TOAs, which could potentially be powered by solar
      panels, have potential as a sustainable disinfection process compared to
      chlorine, ozone, and ultraviolet light.

PMID- 29206076
TI  - Assessment of the ability of V920 recombinant vesicular stomatitis-Zaire
      ebolavirus vaccine to replicate in relevant arthropod cell cultures and vector
      species.
AB  - V920, rVSVDeltaG-ZEBOV-GP, is a recombinant vesicular stomatitis-Zaire ebolavirus
      vaccine which has shown an acceptable safety profile and provides a protective
      immune response against Ebola virus disease (EVD) induced by Zaire ebolavirus in
      humans. The purpose of this study was to determine whether the V920 vaccine is
      capable of replicating in arthropod cell cultures of relevant vector species and
      of replicating in live mosquitoes. While the V920 vaccine replicated well in Vero
      cells, no replication was observed in Anopheles or Aedes mosquito, Culicoides
      biting midge, or Lutzomyia sand fly cells, nor in live Culex or Aedes mosquitoes
      following exposure through intrathoracic inoculation or feeding on a high-titer
      infectious blood meal. The insect taxa selected for use in this study represent
      actual and potential epidemic vectors of VSV. V920 vaccine inoculated into Cx.
      quinquefasciatus and Ae. aegypti mosquitoes demonstrated persistence of
      replication-competent virus following inoculation, consistent with the recognized
      biological stability of the vaccine, but no evidence for active virus replication
      in live mosquitoes was observed. Following administration of an infectious blood
      meal to Ae. aegypti and Cx. quinquefasciatus mosquitoes at a titer several log10
      PFU more concentrated than would be observed in vaccinated individuals, no
      infection or dissemination of V920 was observed in either mosquito species. In
      vitro and in vivo data gathered during this study support minimal risk of the
      vector-borne potential of the V920 vaccine.

PMID- 29206078
TI  - Serological survey of mumps antibodies in adults in the Czech Republic and the
      need for changes to the vaccination strategy.
AB  - Mumps outbreaks, especially in adolescents and young adults, have been reported
      in the Czech Republic. The aim of the presented study was to determine the
      seroprevalence of specific IgG antibodies against mumps in the adult population
      of the Czech Republic. The study was designed as a multicenter serological survey
      of adults aged 18 years and over. Specific IgG antibodies against mumps were
      detected in blood samples using an enzyme-linked immunosorbent assay (ELISA). A
      total of 1,911 serum samples were examined. The overall seropositivity reached
      55.3%. In individual age groups, the highest seropositivity 63% (63.5-65.2%) was
      recorded in adults aged 40 years and over; the lowest seropositivity was found in
      adults aged 18-29 years (27.4%). The difference in seropositivity rate between
      the 18-29 years age group and the 40 years and over age groups was statistically
      significant (p < 0.001). Only the 18-29 years age group included both vaccinated
      and unvaccinated (born in the pre-vaccine era) individuals. In vaccinated
      individuals, seropositivity was reported in only 19.1% of persons; in
      unvaccinated individuals, seropositivity reached 48.2%. Our results demonstrate
      the long-term persistence of antibodies following natural infection and the
      decrease in seropositivity that occurs after vaccination over time. This immunity
      waning may account for the higher susceptibility of adolescents and young adults
      to mumps. Therefore, the current vaccination program in the Czech Republic could
      be considered as less effective. It will be modified with the shifting of the
      second dose of vaccine from two years of age to the preschool age.

PMID- 29206077
TI  - Radiosurgery and stereotactic radiotherapy with cyberknife system for meningioma
      treatment.
AB  - Objective The aim of this work was to evaluate the impact of stereotactic
      radiosurgery/fractionated stereotactic radiotherapy with the Cyberknife system on
      local disease control, clinical outcome and toxicity in patients with meningioma,
      according to the site and histological grade of lesion. From January 2013 to
      April 2017, 52 patients with intracranial meningiomas were treated with the
      Cyberknife system. Twenty-four patients had undergone previous surgery: 38% gross
      total resection, 10% subtotal resection; 27 patients underwent no surgery; 22
      patients had a recurrence of meningioma. Methods Radiosurgery was used for
      lesions smaller than 2 cm, stereotactic radiotherapy for lesions larger than 2
      cm, or smaller but close to a critical site such as the optical chiasm, optic
      pathway or brainstem. Results Local control and clinical outcomes were analysed.
      Median follow-up was 20 months: six patients died, one after re-surgery died from
      post-surgical sepsis, three from heart disease. Progression-free survival had a
      mean value of 38.3 months and overall survival of 41.6 months. We evaluated at 12
      months 28 patients (100% local control); at 24 months 19 patients (89% local
      control); at 36 months nine patients (89% local control). At baseline, 44/52
      patients (85%) were symptomatic: 19 visual disorders, 17 motor disorders, six
      hearing disorders, 10 headache and six epilepsy. Visual symptoms remained
      unchanged in 52%, improved in 32%, resolved in 16%. Headache was improved in 40%,
      resolved in 10%, unchanged in 50%. Epilepsy was resolved in 17%, unchanged in
      33%, worsened in 33%. Conclusions Stereotactic radiosurgery/fractionated
      stereotactic radiotherapy with Cyberknife provides a good local disease control,
      improving visual, hearing and motor symptoms.

PMID- 29206079
TI  - Vienna Vaccine Safety Initiative.

PMID- 29206080
TI  - Understanding forensic psychiatry in healthcare practices and collaboration
      between legal nurse consultants and physicians.
AB  - In 2000, the Institute of Medicine stunned many professionals with their
      published report that noted the vast number of deaths that occur each year in
      hospitals across the United States which reach as many as 98,000. Therefore, it
      comes as no surprise that the healthcare arena faces litigious issues regularly,
      with some specialties budgets being significantly impacted by the cost of
      maintaining liability insurance. Legal Nurse Consultants and forensic physicians
      working in tandem but who work independently from treating clinicians can carry
      out forensic independent medical examinations (IME). This can help to assess the
      validity of malpractice claims, including issues of causation and degree of
      injuries claimed due to the incident(s) and recommend treatment strategies where
      appropriate. Reviews can cover a wide range of issues such as a person's past or
      current testamentary capacity, a prisoner or an accused person's mental health
      and/or mental impairment where necessary sending them for more assessment or
      treatment outside prison. This article argues that independent medical reviews
      are a useful tool that can assist the civil and criminal courts processes.

PMID- 29206081
TI  - Removal of organic matter of electrodialysis reversal brine from a petroleum
      refinery wastewater reclamation plant by UV and UV/H202 process.
AB  - Direct (UV) and hydrogen peroxide-assisted (UV/H2O2) photolysis were investigated
      in bench-scale for removing the organic compounds present in the electrodialysis
      reversal (EDR) brine from a refinery wastewater reclamation plant. In the UV/H2O2
      experiments, a COD:H2O2 molar ratios of 1:1, 1:2 and 1:3 were tested by
      recirculating the brine in the UV reactor for 120 min. Results showed a
      significant reduction in UVA254, whereas no reduction was observed for chemical
      oxygen demand (COD), in the UV process, suggesting great cleavage but limited
      mineralization of the organic matter. UV/H2O2 with C:H2O2 ratio of 1:3 exhibited
      high efficiency in removing the organic matter (COD removal of 92% with an
      electrical energy per removal order (EEO) value of 22 kW h m-3). Although the EDR
      brine has high salinity, no strong scavenging effect of *OH was found in the
      water matrix due to the high concentration of anions, especially chloride and
      bicarbonate. Finally, UV/H2O2 with C:H2O2 ratio of 1:3 and residence time of 120
      min is an efficient alternative for organic matter removal of EDR brine from
      refinery wastewater reclamation plant showing total capital cost (CapEx)
      estimated at US$ 369,653.00 and total operational cost (OpEx), at US$ 1.772 per
      cubic meter of effluent.

PMID- 29206082
TI  - Developmental prosopagnosia with concurrent topographical difficulties: A case
      report and virtual reality training programme.
AB  - Several neuropsychological case studies report brain-damaged individuals with
      concurrent impairments in face recognition (i.e., prosopagnosia) and
      topographical orientation. Recently, individuals with a developmental form of
      topographical disorientation have also been described, and several case reports
      of individuals with developmental prosopagnosia provide anecdotal evidence of
      concurrent navigational difficulties. Clearly, the co-occurrence of these
      difficulties can exacerbate the negative psychosocial consequences associated
      with each condition. This paper presents the first detailed case report of an
      individual (FN) with developmental prosopagnosia alongside difficulties in
      topographical orientation. FN's performance on an extensive navigational battery
      indicated that she primarily has difficulties in the formation and retrieval of
      cognitive maps. We then evaluated the effectiveness of a short-term virtual
      reality training programme and found that she is able to form a cognitive map of
      a particular environment following intense overlearning. Surprisingly, FN's
      performance on a face recognition task also improved following training. While
      the latter finding was unexpected and requires further exploration, the training
      programme reported here may help to alleviate some of the compounded negative
      psychosocial consequences that are associated with difficulties in finding both
      locations and people.

PMID- 29206083
TI  - Tropical surface water quality studies: Implications for the aquatic fate of N
      methyl carbamate pesticides.
AB  - Water quality assessment was conducted on the Ruiru River, a tributary of an
      important tropical river system in Kenya, to determine baseline river conditions
      for studies on the aquatic fate of N-methyl carbamate (NMC) pesticides.
      Measurements were taken at the end of the long rainy season in early June 2013.
      Concentrations of copper (0.21-1.51 ppm), nitrates (2.28-4.89 ppm) and phosphates
      (0.01-0.50 ppm) were detected at higher values than in uncontaminated waters, and
      attributed to surface runoff from agricultural activity in the surrounding area.
      Concentrations of dissolved oxygen (8-10 ppm), ammonia (0.02-0.22 ppm) and
      phenols (0.19-0.83 ppm) were found to lie within normal ranges. The Ruiru River
      was found to be slightly basic (pH 7.08-7.70) with a temperature of 17.8-21.2
      degrees C. The half-life values for hydrolysis of three NMC pesticides
      (carbofuran, carbaryl and propoxur) used in the area were measured under
      laboratory conditions, revealing that rates of decay were influenced by the
      electronic nature of the NMCs. The hydrolysis half-lives at pH 9 and 18 degrees C
      decreased in the order carbofuran (57.8 h) > propoxur (38.5 h) > carbaryl (19.3
      h). In general, a decrease in the electron density of the NMC aromatic ring
      increases the acidity of the N-bound proton removed in the rate-limiting step of
      the hydrolysis mechanism. Our results are consistent with this prediction, and
      the most electron-poor NMC (carbaryl) hydrolyzed fastest, while the most electron
      rich NMC (carbofuran) hydrolyzed slowest. Results from this study should provide
      baseline data for future studies on NMC pesticide chemical fate in the Ruiru
      River and similar tropical water systems.

PMID- 29206084
TI  - Identity crisis in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer
      cells acquire their hallmarks by a pathological Darwinian evolution process built
      on the so-called cancer cell "identity crisis." Here we demonstrate that PAH
      shares the most striking features of the cancer identity crisis: the ectopic
      expression of normally silent tissue-specific genes.

PMID- 29206085
TI  - Reduction in the burden of hospital admissions due to cervical disease from 2003
      2014 in Spain.
AB  - BACKGROUND: Cervix uteri cancer is the 4th most common cancer among women
      worldwide and the second most frequent cancer in women under 45 years old in
      Spain. We aimed to describe the burden of hospital admissions by malignant
      neoplasia (MN) and in situ carcinoma (ISC) of the cervix in Spain from 2003 to
      2014, a 12-year period that included the first years after introduction of an HPV
      vaccination program. METHODS: This epidemiological study reviewed data from the
      Ministry of Health National Surveillance System, which includes more than 98% of
      Spanish hospitals. Hospitalization rate, mortality rate, and case fatality rates
      were calculated per year and age group. RESULTS: We found 74,933 hospitalizations
      due to MN and ISC of the cervix. The average age at hospitalization increased
      significantly during the study period. The average length of hospital stay
      decreased significantly (p<0.001), while hospitalization costs increased. The
      mean hospitalization rate was 27.532 cases per 100,000 women (95% CI: 27.335
      27.729). This rate decreased significantly during the study period. The mean
      mortality rate was 1.418 deaths per 100,000 women (95% CI: 1.373-1.463) and the
      mean case-fatality rate was 5.150% (95% CI: 4.992-5.308). CONCLUSION: Our study
      showed a substantial decrease in the hospitalization burden due to cervical
      disease. This decrease could be attributable to different causes including
      cervical cancer prevention measures, and changes in disease management. Further
      research is needed to confirm the cause. This information could contribute to
      further evaluations of the impact and cost effectiveness analysis of HPV
      vaccination in Spain.

PMID- 29206086
TI  - Early Use of Tacrolimus Extended-Release in a Pediatric Kidney Transplant
      Recipient.
AB  - Tacrolimus extended-release pharmacokinetics and its once-daily formulation
      provide beneficial properties, and its use has been evaluated in the adult kidney
      transplant population. Here, we report a case of successful conversion from
      tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a
      pediatric kidney transplant recipient.

PMID- 29206087
TI  - Alemtuzumab Induction Is Associated With an Equalization of Outcomes Between
      White and African American Kidney Transplant Recipients.
AB  - OBJECTIVES: Our aim was to assess outcomes in White and African American kidney
      transplant recipients after induction with alemtuzumab. MATERIALS AND METHODS: We
      performed a retrospective study of 464 patients who received deceased-donor
      kidney transplants and were induced with alem-tuzumab between March 2006 and May
      2015. We evaluated ethnic influences on patient and graft survival, delayed graft
      function, allograft failure, and rejection. RESULTS: There were 337 White (67.3%)
      and 127 African American (25.3%) patients. We observed no significant differences
      in 1-, 3-, 5-, and 7- year death-censored graft survival. We also observed no
      significant differences in 1-, 3-, and 5-year patient survival rates. Having
      African American ethnicity was not a significant predictor of rejection, graft
      survival, or patient survival. CONCLUSIONS: Our results indicate that recipient
      ethnicity is not a predictor of rejection, graft survival, or patient survival.
      White and African American kidney transplant recipients induced with alemtuzumab
      experienced an equalization of outcomes.

PMID- 29206088
TI  - Hepatic Venous Outflow Obstruction After Living-Donor Liver Transplant: Single
      Center Experience.
AB  - OBJECTIVES: In this study, we share our approach for care of patients with
      hepatic venous outlet obstruction after living-donor liver transplant. MATERIALS
      AND METHODS: We retrospectively examined the demographic, clinical, and
      radiologic data of 35 patients who developed hepatic venous outlet obstruction
      after living-donor liver transplant. Patients were subgrouped on the basis of
      onset (8 patients with early onset [< 30 days posttransplant] and 27 patients
      with late onset [>= 30 days posttransplant]) and postoperative survival (24
      survivors, 11 nonsurvivors). RESULTS: Patients ranged in age from 1 to 61 years
      (24 adults and 11 children). All adult patients had undergone right lobe living
      donor liver transplant. In the pediatric group, 8 had undergone left lateral
      segment and 3 had undergone left lobe living-donor liver transplant. Nineteen
      adult patients and all 11 pediatric patients underwent hepatic venous
      reconstruction, with all procedures based on common large-opening drainage models
      using various vascular graft materials. Development of hepatic venous outlet
      obstruction occurred at mean posttransplant day 233 +/- 298.5 in the adult
      patients and mean posttransplant day 139 +/- 97.8 in the pediatric patients.
      After development of obstruction, the patients underwent 1-6 sessions (1.5 +/-
      1.1 sessions) of balloon angioplasty. After the first balloon angioplasty
      procedure, 25% of the adults and 36.3% of the pediatric patients developed
      recurrence. The early-onset and late-onset subgroups showed statistically
      significant differences in serum albumin (P = .01), underlying causes (P < .001),
      time from transplant to obstruction (P = .02), and time from transplant to last
      visit (P = .02). The survivor and nonsurvivor subgroups showed statistically
      significant differences in total bilirubin (P = .03) and time from transplant to
      last visit (P = .03). CONCLUSIONS: Common large-opening reconstruction minimizes
      hepatic venous outlet obstruction development after living-donor liver
      transplant. Balloon angioplasty and/or stenting is almost always the first option
      in the care of this complication.

PMID- 29206089
TI  - Papillomatosis of the Biliary Tree and Gallbladder: Successful Treatment With
      Repeated Resection and Liver Transplant.
AB  - Intraductal papillary neoplasm of the bile duct is now considered to be a
      specific type of bile duct tumor. The progenitor cells of intraductal papillary
      neoplasms of the bile duct are located in the peribiliary gland, which are
      distributed along the intrahepatic bile duct, extrahepatic bile duct, and
      gallbladder; therefore, these neoplasms could arise in any area. The mainstay of
      treatment for patients with intraductal papillary neoplasm of the bile duct is
      complete surgical resection. Neoplasms involving both lobes of the liver can only
      be treated with liver transplant. There have been 11 reported cases of patients
      with biliary papillomatosis treated with liver transplant. In all of these cases,
      involvement was limited to the bile duct. Herein, we present the first case of
      papillomatosis with extensive involvement in the intrahepatic bile duct, the
      extrahepatic bile duct, and the gallbladder, which was successfully treated with
      repeated resection and liver transplant.

PMID- 29206090
TI  - Utility of Serial Protocol Biopsies Performed After 1 Year in Predicting Long
      Term Kidney Allograft Function According to Histologic Phenotype.
AB  - OBJECTIVES: Prognostic implications of early protocol biopsies have been studied;
      however, the value of late protocol biopsy in predicting graft outcome has not
      been well defined. Here, we compared the effects of early and late protocol
      biopsy histologic findings in stable kidney allografts and aimed to understand
      the significance of "borderline" rejection on allograft function. MATERIALS AND
      METHODS: We studied 261 biopsies from 159 renal transplant recipients who were on
      a steroid-free, calcineurin inhibitor and mycophenolate mofetil regimen and who
      received transplants between 2004 and 2012 with mean follow-up of 5 years. Early
      (between 3 and 9 mo) and subsequent late (between 12 and 24 mo) protocol biopsies
      were performed. Biopsies were classified as normal, interstitial fibrosis and/or
      tubular atrophy, subclinical acute rejection with interstitial fibrosis and/or
      tubular atrophy, and borderline rejection with interstitial fibrosis and/or
      tubular atrophy. A linear mixed-effects model was used to determine the effects
      of early and late protocol biopsies on estimated glomerular filtration rate
      changes, with baseline time for estimated glomerular filtration rate fixed at 12
      months. RESULTS: The adjusted model showed that estimated glomerular filtration
      rate at 3 months, donor age, delayed graft function, and early protocol biopsies
      were associated with baseline estimated glomerular filtration rate at 12 months.
      Estimated glomerular filtration rate changes over time were associated with
      findings of interstitial fibrosis and/or tubular atrophy at early biopsy and
      subclinical acute rejection and borderline rejection at late biopsy. At last
      follow-up, final estimated glomerular filtration rate was significantly
      associated with interstitial fibrosis and/or tubular atrophy at early biopsy and
      with subclinical acute rejection at late biopsy. CONCLUSIONS: Although early
      protocol biopsy predicted baseline estimated glomerular filtration rate, late
      biopsy was important for predicting changes in function over time. In addition, a
      diagnosis of "borderline" rejection on protocol biopsies predicted long-term
      graft function.

PMID- 29206092
TI  - Arginine and aerobic training prevent endothelial and metabolic alterations in
      rats at high risk for the development of the metabolic syndrome - CORRIGENDUM.

PMID- 29206091
TI  - Effects of caffeine administration on sedation and respiratory parameters in
      patients recovering from anesthesia.
AB  - Caffeine has been shown to enhance the speed of recovery from general anesthesia
      in murine models, though data in human patients is lacking. This is a
      retrospective review of intravenous caffeine administration (median dose 150
      [125, 250] mg) to 151 heavily sedated patients in the post-anesthesia recovery
      area, to determine the association between caffeine administration and changes in
      sedation score, respiratory rate, and oxyhemoglobin saturation. Richmond
      Agitation-Sedation Scale (RASS) score, respiratory rate, and oxyhemoglobin
      saturation values were obtained during the 90-minute period prior to and
      following caffeine administration. Generalized estimating equations (GEE) with
      explanatory variables of time, caffeine, and the time-by-caffeine interaction
      were created to assess changes in the variables of interest after caffeine
      administration. Following the administration of caffeine, the RASS scores
      increased (estimate = 0.57, SE = 0.14, p < 0.001) but a trend over time or in the
      interaction effect was not observed, suggesting that the changes in RASS were not
      solely due to the recovery from anesthesia over time. No association was found
      between caffeine administration and changes in respiratory parameters. No adverse
      cardiac events were observed. Our data suggests that intravenous caffeine may
      enhance the speed of recovery following general anesthesia, though future
      prospective trials are necessary to define the optimal dose and timing of
      administration.

PMID- 29206093
TI  - The clinical effectiveness and cost-effectiveness of treat-to-target strategies
      in rheumatoid arthritis: a systematic review and cost-effectiveness analysis.
AB  - BACKGROUND: Treat to target (TTT) is a broad concept for treating patients with
      rheumatoid arthritis (RA). It involves setting a treatment target, usually
      remission or low disease activity (LDA). This is often combined with frequent
      patient assessment and intensive and rapidly adjusted drug treatment, sometimes
      based on a formal protocol. OBJECTIVE: To investigate the clinical effectiveness
      and cost-effectiveness of TTT compared with routine care. DATA SOURCES: Databases
      including EMBASE and MEDLINE were searched from 2008 to August 2016. REVIEW
      METHODS: A systematic review of clinical effectiveness was conducted. Studies
      were grouped according to comparisons made: (1) TTT compared with usual care, (2)
      different targets and (3) different treatment protocols. Trials were subgrouped
      by early or established disease populations. Study heterogeneity precluded meta
      analyses. Narrative synthesis was undertaken for the first two comparisons, but
      was not feasible for the third. A systematic review of cost-effectiveness was
      also undertaken. No model was constructed as a result of the heterogeneity among
      studies identified in the clinical effectiveness review. Instead, conclusions
      were drawn on the cost-effectiveness of TTT from papers relating to these
      studies. RESULTS: Sixteen clinical effectiveness studies were included. They
      differed in terms of treatment target, treatment protocol (where one existed) and
      patient visit frequency. For several outcomes, mixed results or evidence of no
      difference between TTT and conventional care was found. In early disease, two
      studies found that TTT resulted in favourable remission rates, although the
      findings of one study were not statistically significant. In established disease,
      two studies showed that TTT may be beneficial in terms of LDA at 6 months,
      although, again, in one case the finding was not statistically significant. The
      TICORA (TIght COntrol for RA) trial found evidence of lower remission rates for
      TTT in a mixed population. Two studies reported cost-effectiveness: in one, TTT
      dominated usual care; in the other, step-up combination treatments were shown to
      be cost-effective. In 5 of the 16 studies included the clinical effectiveness
      review, no cost-effectiveness conclusion could be reached, and in one study no
      conclusion could be drawn in the case of patients denoted low risk. In the
      remaining 10 studies, and among patients denoted high risk in one study, cost
      effectiveness was inferred. In most cases TTT is likely to be cost-effective,
      except where biological treatment in early disease is used initially. No
      conclusions could be drawn for established disease. LIMITATIONS: TTT refers not
      to a single concept, but to a range of broad approaches. Evidence reflects this.
      Studies exhibit substantial heterogeneity, which hinders evidence synthesis. Many
      included studies are at risk of bias. FUTURE WORK: Future studies comparing TTT
      with usual care must link to existing evidence. A consistent definition of
      remission in studies is required. There may be value in studies to establish the
      importance of different elements of TTT (the setting of a target, the intensive
      use of drug treatments and protocols pertaining to those drugs and the frequent
      assessment of patients). CONCLUSION: In early RA and studies of mixed early and
      established RA populations, evidence suggests that TTT improves remission rates.
      In established disease, TTT may lead to improved rates of LDA. It remains unclear
      which element(s) of TTT (the target, treatment protocols or increased frequency
      of patient visits) drive these outcomes. Future trials comparing TTT with usual
      care and/or different TTT targets should use outcomes comparable with existing
      literature. Remission, defined in a consistent manner, should be the target of
      choice of future studies. STUDY REGISTRATION: This study is registered as
      PROSPERO CRD42015017336. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 29206094
TI  - Long-term follow-up and outcome in patients with recurrent respiratory laryngeal
      papillomatosis.
AB  - INTRODUCTION: Recurrent respiratory papillomatosis is characterized by wart-like
      lesions of the upper airway and is most frequently caused by human papillomavirus
      (HPV). The disease has significant impact on quality of life due to potential
      airway obstruction, dysphonia and the need for serial surgeries. The main
      objective of this study was to describe patient characteristics and long-term
      follow-up data in a Danish cohort with the disease. METHODS: The study was a
      longitudinal retrospective cohort-study using data from electronic medical
      records and a pathology database. RESULTS: A total of 61 adult and four juvenile
      patients were identified. The male-to-female ratio was 2.4. In the adult
      population, the mean age at onset was 45 years. The median number of surgeries
      was four (interquartile range: 2.8). The mean follow-up time was 8.7 years
      (range: 7 days-30 years). Three cases of malignant transformation were observed.
      In the juvenile population, the mean age of onset was 8.5 years (range: 3-12
      years). The mean follow-up time was 11.5 years (range: 2-23 years), and the
      number of surgeries per year at risk was one/year. CO2-laser and microdebrider
      were the surgical techniques usually employed. 43% of histopathologic analyses
      could detect HPV infection (subtype 6 or 11). CONCLUSIONS: More males than
      females suffer from respiratory papillomatosis; age of onset was either in
      childhood or in mid-life. Use of CO2-laser or microdebrider was the preferred
      surgical approach in this cohort. FUNDING: none. TRIAL REGISTRATION: not
      relevant.

PMID- 29206095
TI  - Indications and complications in relation to removal of clavicle implants.
AB  - INTRODUCTION: Implant-related discomfort (soft-tissue irritation, pain and
      cosmetics) is often seen in patients with surgically treated clavicle fracture.
      The aim of this study was to investigate indications, complications,
      functionality and patient satisfaction following implant removal of surgically
      treated clavicle fractures. METHODS: A total of 97 patients (73 males, mean age
      43 years) had a clavicle plate removed at our department between 2007 and 2014. A
      purpose-made questionnaire was used to assess self-perception of cause of implant
      removal, remission, complications and overall satisfaction. Functionality was
      assessed using the Quick DASH score. RESULTS: Two patients died before follow-up
      and were excluded. Five different indications for implant removal were found. A
      total of 65/95 of the patients answered the purpose-made questionnaire; 50/65
      reported satisfaction and 14/65 had a complication following the removal of their
      implant. The mean QuickDASH score was 7 (range: 0-91). Only 18/36 of those with
      pain and soft tissue irritation due to a clavicle plate had complete remission
      after implant removal. CONCLUSIONS: The indications for clavicle plate removal
      are many and mainly subjective. Implant removal in patients following surgically
      treated clavicle fractures generally causes very few complications, and most
      patients seem to experience a positive effect. However, it is important to inform
      the patient of the risk of no remission or even a worsening, which is not an
      uncommon occurrence. FUNDING: none. TRIAL REGISTRATION: not relevant.

PMID- 29206096
TI  - Danish translation of the Foot and Ankle Outcome Score.
AB  - INTRODUCTION: The Foot and Ankle Outcome Score (FOAS) is a standardized
      instrument used to report on injury-specific clinical status following foot- and
      ankle-related problems. The primary aim of this study was to translate and
      conduct a cross-cultural adaptation of the FAOS into a Danish setting, including
      testing absolute agreement and the test-retest reliability of the questionnaire.
      METHODS: Translation of the FAOS questionnaire was ?carried out according to the
      Principles of Good Practice for the Translation and Cultural Adaptation Process
      for Patient-?Reported Outcomes Measures: report of the Society for
      Pharmacoeconomics and Outcomes Research Task Force ?for Translation and Cultural
      Adaptation. RESULTS: No major disagreements were observed between the original
      and translated version of the FAOS questionnaire during the translation procedure
      and cognitive interview. A total of 51 patients were included in the reliability
      testing procedure. The test-retest reliability was high: pain interclass
      correlation coefficient (ICC) 0.88 (95% confidence interval (CI): 0.79-0.93),
      symptoms ICC 0.95 (95% CI: 0.91-0.97), activities of daily living ICC 0.95 (95%
      CI: 0.90-0.97), sport ICC 0.95 (95% CI: 0.90-0.97) and quality of life ICC 0.94
      (95% CI: 0.90-0.97). The Bland-Altman plots showed good agreement between test
      and retest for all five subscales. CONCLUSIONS: The translation of the FAOS
      questionnaire into Danish was done in accordance with best practice and has
      excellent repeatability in patients treated for ankle fractures. FUNDING: none.
      TRIAL REGISTRATION: not relevant.

PMID- 29206097
TI  - A closed-claim analysis of complaints after paediatric antebrachial fractures.
AB  - INTRODUCTION: Antebrachial fractures in children (AFC) are common and account for
      one third of all paediatric fractures. The Danish Patient Compensation
      Association (PCA) receives complaints from patients who believe that they have
      sustained injuries due to potential malpractice or unfortunate circumstances.
      Case files on AFC from the PCA were assessed to identify causality and factors
      contributing to complaints and potential malpractice. METHODS: A closed-claim
      analysis was performed in 138 cases with the diagnosis codes DS52.2 through
      DS52.6. RESULTS: The most frequent complaints were fracture re-displacement (n =
      49) and dissatisfaction with an otherwise correctly treated injury (n = 30).
      Doctor's delay due to missed primary diagnosis was found to be a median of 63
      days. Complaints about surgery were almost equally distributed between K-wire and
      intramedullary nails, and unequally distributed for conservative treatment
      between splinting (n = 29) and casting (n = 10). Two thirds of the in-juries were
      unacknowledged and evaluated as light injuries or no injury. One third of the
      complaints were acknowledged; the majority of which were both-bone fractures.
      CONCLUSIONS: Two thirds of all complaints were due to normal fracture sequelae;
      thus, patient anticipation should be accommodated by thorough patient
      information. Mid-diaphyseal fractures of the forearm are overrepresented among
      the acknowledged complaints. Casting seems to be preferred to splinting. However,
      more awareness of these fractures using routinely performed radiographs at the
      first visit to the emergency room and at follow-up could avoid complaints as well
      as doctor's delay. FUNDING: none. ?TRIAL REGISTRATION: not relevant.

PMID- 29206098
TI  - Monoclonal B-cell lymphocytosis; not the same as B-cell chronic lymphocytic
      leukaemia.
AB  - INTRODUCTION: Depending on the location and the extent of disease, mature B-cell
      disorders can be divided into ?benign monoclonal B-cell lymphocytosis (MBL),
      chronic ?lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL).
      Whereas SLL is characterised by its location outside the blood stream, MBL is
      distinguished from CLL by a monoclonal B-cell count below 5 * 109/l. Due to its
      low tendency to transform into CLL, correct diagnosis of MBL is essential. We
      hypothesised that this might not always be the case. METHODS: This study includes
      data on monoclonal B-lymphocyte count based on diagnostic flow cytometry from
      patients diagnosed in the period from 1 January 2011 to 31 December 2016 at the
      Department of Haematology, Aarhus University Hospital, Denmark. A total of 69
      patients had less than 5 * 109/l monoclonal B-cells with a CLL-like
      ?immunophenotype in peripheral blood. All cases were classified based on the 2008
      WHO criteria and evaluated according to the clinical diagnosis of CLL, MBL or SLL
      in the medical records. A total of 24 of the 69 patients were classified as MBL.
      RESULTS: In the study cohort, 12 (50%) patients classified as MBL were diagnosed
      accurately with MBL, whereas nine (38%) were diagnosed with CLL. CONCLUSIONS: The
      findings of this study indicate that a sizeable fraction of MBL patients are
      diagnosed inaccurately with CLL, even after the introduction of the MBL
      diagnosis. FUNDING: The Danish Cancer Society. TRIAL REGISTRATION: not relevant.

PMID- 29206099
TI  - Implementation of evidence-based knowledge in general practice.
AB  - BackgroundKeeping up with the evidence and implementing it into the daily care
      for patients are fundamental prerequisites for delivering a high quality of care
      in general practice. However, despite many years of research into dissemination
      and implementation of evidence-based recommendations, significant challenges
      remain. In recent years, organisational factors have become widely acknowledged
      as vitally important for ensuring successful implementation. Further knowledge is
      needed to understand more about which factors affect the seeking and
      implementation of evidence-based knowledge in general practice.  AimThe overall
      aim was to investigate how evidence-based knowledge is sought and implemented in
      general practice and to analyse associations with GP characteristics and quality
      of care. Three separate studies, each covering a specific part of the overall
      aim, were undertaken: I. To examine how GPs implement clinical practice
      guidelines in everyday clinical practice, and how implementation approaches
      differ between practices.II. To assess GPs' information seeking behaviour with
      regard to the use and perceived importance of scientific medical information
      sources and to investigate associations with GP characteristics.III. To
      investigate if there are associations between specific formalised implementation
      activities within general practice and quality of care - exemplified by the use
      of spirometry testing among first-time users of medication against obstructive
      lung diseases. MethodsThe study was designed as a mixed methods study combining
      qualitative interviews, questionnaire and register data. Study I was a
      qualitative interview study that involved purposefully selected GPs representing
      seven different practices. The interviews were analysed using systematic text
      condensation, and results were used to qualify the development of a national
      survey of general practitioners regarding their seeking and implementation of
      evidence-based knowledge. This survey was distributed on December 4th to all GPs
      in Denmark who at the time had an email address registered at the Danish
      Organisation of GPs (N = 3,440). Study II was a cross-sectional study based on
      the survey data. In study III, while also applying a cross-sectional design, data
      on quality of care from national registers were linked to data from the survey.
      Spirometry testing among patients redeeming a first-time prescription for
      medication targeted obstructive lung diseases (R03 medication) was used as an
      example of an evidence-based recommendation, and thereby as a proxy for quality
      of care.ResultsStudy I: The analysis of the semi-structured individual interviews
      revealed that approaches to implementation of clinical guidelines differed
      substantially between practices. Overall, three different approaches were
      identified, depending on the degree to which implementation was collectively and
      formally organised. In some practices, the GPs prioritised time and resources for
      collective implementation activities and organized their everyday practice to
      support these activities. In other practices, GPs discussed guidelines
      collectively, but left the application up to the individual GP whilst others saw
      no need for discussion or collective activities depending entirely on the
      individual GP's decision on whether and how to manage implementation. The GPs'
      attitudes to consistency in patient care appeared to be closely related to their
      approach to implementation. Study II: A total of 1,580 (46.4%) GPs responded to
      the questionnaire. Results showed that GPs' information-seeking behaviour is
      associated with gender, age and practice form. Single-handed GPs use their
      colleagues as an information source significantly less than GPs working in
      partnership practices, and they do not use other sources more frequently.
      Compared with their younger colleagues, GPs aged over 44 years are less likely to
      seek information from colleagues, guidelines and websites, but more likely to
      seek information from medical journals. Male and female GPs seek information
      equally frequently. However, whereas male GPs are more likely than female GPs to
      find that pharmaceutical sales representative and non-refundable CME meetings are
      important sources in keeping medically updated, they are less likely to find that
      colleagues, refundable CME meetings, guidelines and drug information websites are
      important.Study III: GPs from 1,114 practices (58%) responded to the
      questionnaire, and 33,788 patients were linked to a responding practice. In
      partnership practices, compared with less frequent or no meetings, weekly
      interdisciplinary and weekly GP meetings were significantly associated with
      higher quality of care measured by patients' OR of having spirometry performed.
      Furthermore, the development of practice protocols and standard recordings in the
      EMR in a range of disease areas, compared with only a few areas or none at all,
      were significantly associated with quality of care. The effect of formalised
      implementation activities was not as evident in single-handed practices as in
      partnerships.ConclusionThe results show how GP characteristics could be taken
      into consideration when disseminating scientific medical information to better
      ensure that patients are provided with medically updated, high-quality care.
      Further, the study demonstrates the variation in approaches to implementation of
      evidence-based knowledge in general practices. This variation should be taken
      into consideration when developing quality improvement initiatives or
      interventions. Thus, knowledge of which approaches are used in specific practice
      settings could prove essential when deciding where to put the focus and support.
      Finally, the study indicates that important factors to be considered in that
      respect are the presence of formalised implementation activities in the practices
      as some degree of formalisation appears to contribute to sustaining a high
      quality of care by supporting implementation of evidence-based recommendations.

PMID- 29206100
TI  - Asthma and Pregnancy: Possible to prevent complications?- With Special reference
      to the impact of obesity and type of airwayinflammation
AB  - Background Asthma is a serious global health issue and the most prevalent chronic
      disorder among Danish pregnant women. Exacerbations of asthma during pregnancy
      have been associated with increased risk of adverse pregnancy and perinatal
      outcomes, and by that making asthma a potential serious medical condition during
      pregnancy. Monitoring of asthma every four to six weeks is recommended during
      pregnancy, although evidence is lacking that following this recommendation will
      improve pregnancy outcome and, not least, be beneficial for all pregnant women
      with asthma.Aim The overall aim of the present thesis was to gain more knowledge
      of the interaction between asthma and pregnancy. The specific research questions
      were to identify pregnancies with low risk of an exacerbation during pregnancy,
      to identify risk factors for an exacerbation during pregnancy, and to compare the
      adverse pregnancy and perinatal outcomes in women without asthma and women with
      asthma monitored closely as recommended during pregnancy. Methods In study I and
      II, determinants of pregnancies with low risk of an exacerbation and maternal
      pregnancy-related risk factors for an exacerbations were investigated in a large
      prospective cohort study with 1.283 women with asthma. The Management of Asthma
      during Pregnancy (MAP) was initiated in 2007, and all pregnant women referred to
      Hvidovre Hospital have since then received an invitation to participate. Women
      were followed-up every four weeks with assessment of asthma control and
      adjustment of medication if necessary. In study III, the potential differences in
      airway hyperresponsiveness and airway inflammation, in participants (n=50) from
      the MAP cohort, were investigated in a post-partum examination. In study IV, the
      effect of maternal asthma on obstetrical and perinatal outcomes was investigated
      in a large case-control study, with 938 cases i.e. women with asthma from the MAP
      cohort, and 2.778 controls i.e. women without asthma.Results No history of pre
      pregnancy exacerbations, no prescribed controller medication, and clinically
      stable asthma at the first visit was determinants of pregnancies with a low risk
      of an asthma exacerbation during pregnancy (study I). Excessive gestational
      weight gain (GWG) in first trimester was associated with increased risk of an
      asthma exacerbation during pregnancy; furthermore, the impact of GWG was dose
      dependent (Study II). In study III, women experiencing an asthma exacerbation
      during pregnancy had more pronounced airway hyperresponsiveness and were more
      often non-atopic. Finally, in study IV, the overall risk of adverse obstetrical
      and perinatal outcomes in women with asthma monitored closely during pregnancy
      was low. Conclusion Women with no history of pre-pregnancy exacerbations, no
      prescribed controller medication, and clinically stable asthma at the first visit
      have a very low risk of an exacerbation. Furthermore, excessive GWG, airway
      hyperresponsiveness and being non-atopic are risk factors for exacerbations of
      asthma during pregnancy. However, the overall risk of adverse obstetrical and
      perinatal outcomes in women with actively managed asthma during pregnancy is
      comparable to women without asthma

PMID- 29206101
TI  - Serotonin enhances excitability and gamma frequency temporal integration in mouse
      prefrontal fast-spiking interneurons.
AB  - The medial prefrontal cortex plays a key role in higher order cognitive functions
      like decision making and social cognition. These complex behaviors emerge from
      the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs)
      control the timing of excitatory neuron firing via somatic inhibition and
      generate gamma (30-100 Hz) oscillations. Therefore, factors that regulate how
      FSIs respond to gamma-frequency input could affect both prefrontal circuit
      activity and behavior. Here, we show that serotonin (5HT), which is known to
      regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying
      potassium conductance in FSIs. This leads to depolarization, increased input
      resistance, enhanced spiking, and slowed decay of excitatory post-synaptic
      potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially
      enhanced temporal summation and firing elicited by gamma frequency inputs. These
      findings show how changes in passive membrane properties can affect not only
      neuronal excitability but also the temporal filtering of synaptic inputs.

PMID- 29206102
TI  - eIF1A residues implicated in cancer stabilize translation preinitiation complexes
      and favor suboptimal initiation sites in yeast.
AB  - The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in
      favorable context, and AUG recognition stabilizes a closed PIC conformation. The
      unstructured N-terminal tail (NTT) of yeast eIF1A deploys five basic residues to
      contact tRNAi, mRNA, or 18S rRNA exclusively in the closed state. Interestingly,
      EIF1AX mutations altering the human eIF1A NTT are associated with uveal melanoma
      (UM). We found that substituting all five basic residues, and seven UM-associated
      substitutions, in yeast eIF1A suppresses initiation at near-cognate UUG codons
      and AUGs in poor context. Ribosome profiling of NTT substitution R13P reveals
      heightened discrimination against unfavorable AUG context genome-wide. Both R13P
      and K16D substitutions destabilize the closed complex at UUG codons in
      reconstituted PICs. Thus, electrostatic interactions involving the eIF1A NTT
      stabilize the closed conformation and promote utilization of suboptimal start
      codons. We predict UM-associated mutations alter human gene expression by
      increasing discrimination against poor initiation sites.

PMID- 29206103
TI  - A population of innate myelolymphoblastoid effector cell expanded by inactivation
      of mTOR complex 1 in mice.
AB  - Adaptive autoimmunity is restrained by controlling population sizes and
      pathogenicity of harmful clones, while innate destruction is controlled at
      effector phase. We report here that deletion of Rptor in mouse hematopoietic
      stem/progenitor cells causes self-destructive innate immunity by massively
      increasing the population of previously uncharacterized innate
      myelolymphoblastoid effector cells (IMLECs). Mouse IMLECs are CD3-B220-NK1.1
      Ter119- CD11clow/-CD115-F4/80low/-Gr-1- CD11b+, but surprisingly express high
      levels of PD-L1. Although they morphologically resemble lymphocytes and actively
      produce transcripts from Immunoglobulin loci, IMLECs have non-rearranged Ig loci,
      are phenotypically distinguishable from all known lymphocytes, and have a gene
      signature that bridges lymphoid and myeloid leukocytes. Rptor deletion unleashes
      differentiation of IMLECs from common myeloid progenitor cells by reducing
      expression of Myb. Importantly, IMLECs broadly overexpress pattern-recognition
      receptors and their expansion causes systemic inflammation in response to Toll
      like receptor ligands in mice. Our data unveil a novel leukocyte population and
      an unrecognized role of Raptor/mTORC1 in innate immune tolerance.

PMID- 29206106
TI  - Effect of chain stiffness on the structure of single-chain polymer nanoparticles.
AB  - Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by
      purely intramolecular cross-linking of single polymer chains. By means of
      computer simulations, we investigate the conformational properties of SCNPs as a
      function of the bending stiffness of their linear polymer precursors. We
      investigate a broad range of characteristic ratios from the fully flexible case
      to those typical of bulky synthetic polymers. Increasing stiffness hinders
      bonding of groups separated by short contour distances and increases looping over
      longer distances, leading to more compact nanoparticles with a structure of
      highly interconnected loops. This feature is reflected in a crossover in the
      scaling behaviour of several structural observables. The scaling exponents change
      from those characteristic for Gaussian chains or rings in theta-solvents in the
      fully flexible limit, to values resembling fractal or 'crumpled' globular
      behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are
      weakly deformable regions that can be seen as disordered analogues of domains in
      disordered proteins. Increasing stiffness leads to bigger and less deformable
      domains. Surprisingly, the scaling behaviour of the domains is in all cases
      similar to that of Gaussian chains or rings, irrespective of the stiffness and
      degree of cross-linking. It is the spatial arrangement of the domains which
      determines the global structure of the SCNP (sparse Gaussian-like object or
      crumpled globule). Since intramolecular stiffness can be varied through the
      specific chemistry of the precursor or by introducing bulky side groups in its
      backbone, our results propose a new strategy to tune the global structure of
      SCNPs.

PMID- 29206107
TI  - Statistical thermodynamics and magnetic moments of Landau quantized group VI
      dichalcogenides.
AB  - This work is focused on the determination of the Helmholtz free energy and the
      magnetic moments of the 'Dirac-like' group VI dichalcogenides subject to Landau
      quantization. We employ a technique described by Wilson to relate the free energy
      to the Green's function for the dichalcogenides in a high magnetic field, which
      was recently evaluated explicitly in terms of elementary functions. In the course
      of this analysis, the partition function is determined as a function of the
      magnetic field as well. The results exhibit the role of the quantizing magnetic
      field in the Helmholtz free energy at arbitrary temperature, and they are also
      employed to obtain the magnetic moments of the dichalcogenides. Explicit analytic
      formulas characteristic of de Haas-van Alphen oscillatory phenomenology are
      presented in the degenerate limit, and nondegenerate Landau quantization effects
      are also presented for the dichalcogenide magnetic moments.

PMID- 29206105
TI  - Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino
      acid.
AB  - TRPV1 channels support the detection of noxious and nociceptive input. Currently
      available functional and structural data suggest that TRPV1 channels have two
      gates within their permeation pathway: one formed by a 'bundle-crossing' at the
      intracellular entrance and a second constriction at the selectivity filter. To
      describe conformational changes associated with channel gating, the fluorescent
      non-canonical amino acid coumarin-tyrosine was genetically encoded at Y671, a
      residue proximal to the selectivity filter. Total internal reflection
      fluorescence microscopy was performed to image the conformational dynamics of the
      channels in live cells. Photon counts and optical fluctuations from coumarin
      encoded within TRPV1 tetramers correlates with channel activation by capsaicin,
      providing an optical marker of conformational dynamics at the selectivity filter.
      In agreement with the fluorescence data, molecular dynamics simulations display
      alternating solvent exposure of Y671 in the closed and open states. Overall, the
      data point to a dynamic selectivity filter that may serve as a gate for
      permeation.

PMID- 29206108
TI  - Fabrication and characterisation of ligand-functionalised ultrapure monodispersed
      metal nanoparticle nanoassemblies employing advanced gas deposition technique.
AB  - Here, we report for the first time the fabrication of ligand-functionalised
      ultrapure monodispersed metal nanoparticles (Au, Cu, and Pt) from their pure
      metal precursors using the advanced gas deposition technique. The experimental
      conditions during nanoparticle formation were adjusted in order to obtain
      ultrafine isolated nanoparticles on different substrates. The morphology and
      surface analysis of the as-deposited metal nanoparticles were investigated using
      scanning electron microscopy, x-ray diffraction and Fourier transform infra-red
      spectroscopy, which demonstrated the formation of highly ordered pure crystalline
      nanoparticles with a relatively uniform size distribution of ~10 nm (Au), ~4 nm
      (Cu) and ~3 nm (Pt), respectively. A broad range of organic ligands containing
      thiol or amine functional groups were attached to the nanoparticles to form
      continuous networks of nanoparticle-ligand nanoassemblies, which were
      characterised by scanning electron microscopy and x-ray photoelectron
      spectroscopy. The electrical resistance of the functional nanoassemblies
      deposited in the gap spacing of two microfabricated parallel Au electrodes
      patterned on silicon substrates ranged between tens of kOmega and tens of MOmega,
      which is suitable for use in many applications including (bio)chemical sensors,
      surface-enhanced Raman spectroscopy and molecular electronic rectifiers.

PMID- 29206109
TI  - Methodological considerations in the calculation of the rate of force development
      scaling factor.
AB  - OBJECTIVE: Within this methodological study, we aimed to explore the effects of
      seven different commonly applied routines for rate of force development (RFD)
      calculation on the calculation of rate of force development scaling factor (RFD
      SF) and r 2 and the between session reliability of RFD-SF in three different
      muscle groups. APPROACH: We tested grip force muscles, elbow extensors and knee
      extensors of 13 healthy subjects asking them to produce around 120 rapid
      isometric force pulses per muscle to varying submaximal amplitudes. Then, we
      applied different filtering and analysis procedures, such as different filtering
      cut-off frequencies (no filter, 5 Hz cut-off, 10 Hz cut-off) and time windows
      during which RFD was calculated (0-50 ms, 0-75 ms, 0-100 ms and time from onset
      of contraction to peak force (PF) value). RFD-SF and r 2 were obtained from the
      relationship between the PF and the corresponding RFD. RESULTS: Our results
      showed that the magnitude of the calculated RFD-SF and r 2 values significantly
      differed among different RFD calculation methods (p  <  0.0005), but that r 2 was
      high in most applied methods (RFD-SF ranged between 4.6 and 17.7, while r 2
      ranged between 0.63 and 0.98). Regardless of the tested muscle group and applied
      method to calculate RFD, the reliability of the calculated RFD-SF was moderate
      (0.5  <  ICC3,1  <  0.75) to good (ICC3,1  >  0.75). The highest r 2, highest
      ICC, lowest SEM% and MDD% were observed in case of RFD calculated during first
      100 ms and when cut-off filter at 5 Hz was applied, indicating those two methods
      as the most appropriate ones. SIGNIFICANCE: Our study contributes to the
      establishment of methodological suggestions that will help in maximizing the
      reliability of RFD-SF measurements, collecting normative data, and comparing
      results among different populations and lab settings.

PMID- 29206110
TI  - Pressure-induced metallization in layered ReSe<sub>2</sub>.
AB  - The evolution of crystal structure and electrical transport properties of
      distorted layered transition metal dichalcogenide ReSe2 was studied under high
      pressure up to ? 90 GPa by Raman spectroscopy and electrical resistivity
      measurements accompanied by ab initio electronic band structure calculations.
      Raman spectroscopy studies indicate isostructural phase transition due to layer
      sliding at ~ 7 GPa to the distorted 1T-phase which remains stable up to the
      highest in these experiments pressures. Direct band gap semiconductor at ambient
      conditions, ReSe2 undergoes pressure-induced metallization at pressure ~ 35 GPa
      in agreement with ab initio calculations. Resistivity measurements performed at
      different loading conditions reveal possible emergence of superconductivity which
      is most likely not intrinsic property of ReSe2 but it is rather conditioned by
      internal stresses upon compression.

PMID- 29206111
TI  - Optical proximity correction (OPC) in near-field lithography with pixel-based
      field sectioning time modulation.
AB  - Subwavelength features have been successfully demonstrated in near-field
      lithography. In this study, the point spread function (PSF) of a near-field beam
      spot from a plasmonic ridge nanoaperture is discussed with regard to the complex
      decaying characteristic of a non-propagating wave and the asymmetry of the field
      distribution for pattern design. We relaxed the shape complexity of the field
      distribution with pixel-based optical proximity correction (OPC) for simplifying
      the pattern image distortion. To enhance the pattern fidelity for a variety of
      arbitrary patterns, field-sectioning structures are formulated via convolutions
      with a time-modulation function and a transient PSF along the near-field dominant
      direction. The sharpness of corners and edges, and line shortening can be
      improved by modifying the original target pattern shape using the proposed
      approach by considering both the pattern geometry and directionality of the field
      decay for OPC in near-field lithography.

PMID- 29206104
TI  - The Human Cell Atlas.
AB  - The recent advent of methods for high-throughput single-cell molecular profiling
      has catalyzed a growing sense in the scientific community that the time is ripe
      to complete the 150-year-old effort to identify all cell types in the human body.
      The Human Cell Atlas Project is an international collaborative effort that aims
      to define all human cell types in terms of distinctive molecular profiles (such
      as gene expression profiles) and to connect this information with classical
      cellular descriptions (such as location and morphology). An open comprehensive
      reference map of the molecular state of cells in healthy human tissues would
      propel the systematic study of physiological states, developmental trajectories,
      regulatory circuitry and interactions of cells, and also provide a framework for
      understanding cellular dysregulation in human disease. Here we describe the idea,
      its potential utility, early proofs-of-concept, and some design considerations
      for the Human Cell Atlas, including a commitment to open data, code, and
      community.

PMID- 29206113
TI  - Design, synthesis and crystallographic study of novel indole-based cyano
      derivatives as key building blocks for heteropolycyclic compounds of major
      complexity.
AB  - A four-stage reaction sequence has been designed and developed for the synthesis
      of highly functionalized enolate esters as key building blocks for the synthesis
      of novel heteropolycyclic compounds of potential pharmaceutical value. The
      sequence starts with simple commercially available indoles and proceeds via 3
      (indol-3-yl)-3-oxopropanenitriles, which react with 2-bromobenzaldehyde to form
      the corresponding chalcones; these are readily reduced to dihydrochalcones, which
      are in turn acylated to form the enolate esters. The compounds in this sequence
      have been characterized by IR and 1H and 13C NMR spectroscopy, by mass
      spectrometry and by elemental analysis. The molecular and supramolecular
      structures are reported for representative examples, namely (E)-3-(2-bromophenyl)
      2-(1-methyl-1H-indole-3-carbonyl)acrylonitrile, C19H13BrN2O, (Ib), (2RS)-2-(2
      bromobenzyl)-3-(1-methyl-1H-indol-3-yl)-3-oxopropanenitrile, C19H15BrN2O, (IIb),
      and (2RS)-3-(1-benzyl-1H-indol-3-yl)-2-(2-bromobenzyl)-3-oxopropanenitrile,
      C25H19BrN2O, (IIc), the latter two of which crystallize with Z' = 2, and (E)-1-(1
      acetyl-1H-indol-3-yl)-3-(2-bromophenyl)-2-cyanoprop-1-en-1-yl acetate,
      C22H17BrN2O, (III), and (E)-1-(1-benzyl-1H-indol-3-yl)-3-(2-bromophenyl)-2
      cyanoprop-1-en-1-yl benzoate, C32H23BrN2O, (IV). The structure of the related
      chalcone (E)-2-benzoyl-3-(2-bromophenyl)prop-2-enenitrile, (V), has been
      redetermined at 100 K, where it is monoclinic, as opposed to the triclinic form
      reported at ambient temperature.

PMID- 29206112
TI  - Richard E. Marsh (1922-2017).

PMID- 29206114
TI  - A new copper(II) coordination polymer containing chains of interconnected paddle
      wheel antiferromagnetic clusters.
AB  - The construction of supramolecular architectures based on inorganic-organic
      coordination frameworks with weak noncovalent interactions has implications for
      the rational design of functional materials. A new crystalline binuclear
      copper(II) one-dimensional polymeric chain, namely catena-poly[[[tetrakis(MU-4
      azaniumylbutanoato-kappa2O:O')dicopper(II)(Cu-Cu)]-MU-chlorido
      [diaquadichloridocopper(II)]-MU-chlorido] bis(perchlorate)],
      {[Cu3Cl4(C4H9NO2)4(H2O)2](ClO4)2}n, was obtained by the reaction of 4
      aminobutyric acid (GABA) with CuCl2.2H2O in aqueous solution. The structure was
      established by single-crystal X-ray diffraction and was also characterized by IR
      spectroscopy and magnetic measurements. The crystal structure consists of
      [{Cu2(GABA)4}{CuCl4(H2O)2}]+ cations and isolated perchlorate anions. Two
      symmetry-related CuII centres are bridged via carboxylate O atoms into a
      classical paddle-wheel configuration, with a Cu...Cu distance of 2.643 (1) A,
      while bridging Cl atoms complete the square-pyramidal geometry of the metal
      atoms. The Cl atoms connect the paddlewheel moieties to a second CuII atom lying
      on an octahedral site, resulting in infinite helical chains along the c axis. The
      packing motif exhibits channels containing free perchlorate anions. The crystal
      structure is stabilized by hydrogen bonds between the perchlorate anions, the
      coordinated water molecules and the ammonium groups of the polymeric chains. The
      magnetic analysis of the title compound indicates a nontrivial antiferromagnetic
      behaviour arising from alternating weak-strong antiferromagnetic coupling between
      neighbouring CuII centres.

PMID- 29206115
TI  - Role of halogen-halogen contacts in the crystal structures of three new solvates
      of the drug oxyclozanide.
AB  - Halogen-halogen contacts are electrostatic in nature and exhibit directionality
      similar to hydrogen bonds. Oxyclozanide [systematic name: 2,3,5-trichloro-N-(3,5
      dichloro-2-hydroxyphenyl)-6-hydroxybenzamide] is a drug used for the treatment of
      fascioliasis in domestic animals. The molecule carries five chlorine substituents
      and represents an ideal candidate for the study of halogen bonds in the crystal.
      Three new crystalline solvates of oxyclozanide, namely, oxyclozanide benzene
      hemisolvate, C13H6Cl5NO3.0.5C6H6, (I), oxyclozanide xylene hemisolvate,
      C13H6Cl5NO3.0.5C8H10, (II), and oxyclozanide toluene hemisolvate,
      C13H6Cl5NO3.0.5C7H8, (III), were structurally characterized. In this context, the
      crystal structure of oxyclozanide chlorobenzene hemisolvate,
      C13H6Cl5NO3.0.5C6H5Cl, (IV), was redetermined based on intensity data collected
      at 100 K. In all four solvates, the cocrystallized solvent molecules are located
      on crystallographic inversion centres. Solvates (I)-(IV) exhibit similar one
      dimensional hydrogen-bonded chains generated by O-H...O, O-H...Cl and Cl...Cl
      interactions. The extension of these one-dimensional chains into two-dimensional
      layers is promoted by Cl...Cl and C-H...pi contacts. Solvates (III) and (IV) are
      isostructural and differ from (I) and (II) with respect to subtle details
      concerning the intermolecular contacts.

PMID- 29206116
TI  - New pharmaceutical salts containing pyridoxine.
AB  - Two mixed crystals were obtained by crystallizing the active pharmaceutical
      ingredient pyridoxine [systematic name: 4,5-bis(hydroxymethyl)-2-methylpyridin-3
      ol, PN] with (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid (ferulic acid)
      and 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid). PN and the coformers
      crystallize in the form of pharmaceutical salts in a 1:1 stoichiometric ratio,
      namely 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridin-1-ium (E)-3-(4-hydroxy-3
      methoxyphenyl)prop-2-enoate, C8H12NO3+.C9H9O5-, and 3-hydroxy-4,5
      bis(hydroxymethyl)-2-methylpyridin-1-ium 4-hydroxy-3,5-dimethoxybenzoate
      monohydrate, C8H12NO3+.C10H11O5-.H2O, the proton exchange between PN and the
      acidic partner being supported by the differences of the pKa values of the two
      components and by the C-O bond lengths of the carboxylate groups. Besides complex
      hydrogen-bonding networks, pi-pi interactions between aromatic moieties have been
      found to be important for the packing architecture in both crystals. Hirshfeld
      surface analysis was used to explore the intermolecular interactions in detail
      and compare them with the interactions found in similar pyridoxine/carboxylic
      acid salts.

PMID- 29206117
TI  - Synthesis, crystal structures and properties of the new compounds K7-xAg1+x(XO4)4
      (X = Mo, W).
AB  - Two new isostructural compounds, namely heptapotassium silver
      tetrakis(tetraoxomolybdate), K7-xAg1+x(MoO4)4 (0 <= x <= 0.4), and heptapotassium
      silver tetrakis(tetraoxotungstate), K7-xAg1+x(WO4)4 (0 <= x <= 0.4), have been
      synthesized and found to crystallize in the polar space group P63mc (Z = 2) with
      the unit-cell dimensions a = 12.4188 (2) and c = 7.4338 (2) A for
      K6.68Ag1.32(MoO4)4 (single-crystal data), and a = 12.4912 (5) and c = 7.4526 (3)
      A for K7Ag(WO4)4 (Rietveld analysis data). Both structures represent a new
      structure type, with characteristic [K1(XO4)6] 'pinwheels' of K1O6 octahedra and
      six XO4 tetrahedra (X = Mo, W) connected by common opposite faces into columns
      along the c axes. The octahedral columns are linked to each other through Ag1O4
      tetrahedra along with the K2 and K3/Ag2 polyhedra, forming the polar rods
      (...Ag1O4-X1O4-empty octahedron-Ag1O4...). Ag1 is located almost at the centre of
      the largest face of its coordination tetrahedron and seems to have some mobility.
      The new structure type is related to the Ba6Nd2Al4O15 and CaBaSiO4 types, and to
      other structures of the alpha-K2SO4-glaserite family. The differential scanning
      calorimetry (DSC) and second harmonic generation (SHG) results show that both
      compounds undergo first-order phase transformations to high-temperature
      centrosymmetric phases.

PMID- 29206118
TI  - Structural and computational analysis of intermolecular interactions in a new 2
      thiouracil polymorph.
AB  - The crystallization and characterization of a new polymorph of 2-thiouracil by
      single-crystal X-ray diffraction, Hirshfeld surface analysis and periodic density
      functional theory (DFT) calculations are described. The previously published
      polymorph (A) crystallizes in the triclinic space group P?overline{1}, while that
      described herein (B) crystallizes in the monoclinic space group P21/c. Periodic
      DFT calculations showed that the energies of polymorphs A and B, compared to the
      gas-phase geometry, were -108.8 and -29.4 kJ mol-1, respectively. The two
      polymorphs have different intermolecular contacts that were analyzed and are
      discussed in detail. Significant differences in the molecular structure were
      found only in the bond lengths and angles involving heteroatoms that are involved
      in hydrogen bonds. Decomposition of the Hirshfeld fingerprint plots revealed that
      O...H and S...H contacts cover over 50% of the noncovalent contacts in both of
      the polymorphs; however, they are quite different in strength. Hydrogen bonds of
      the N-H...O and N-H...S types were found in polymorph A, whereas in polymorph B,
      only those of the N-H...O type are present, resulting in a different packing in
      the unit cell. QTAIM (quantum theory of atoms in molecules) computational
      analysis showed that the interaction energies for these weak-to-medium strength
      hydrogen bonds with a noncovalent or mixed interaction character were estimated
      to fall within the ranges 5.4-10.2 and 4.9-9.2 kJ mol-1 for polymorphs A and B,
      respectively. Also, the NCI (noncovalent interaction) plots revealed weak
      stacking interactions. The interaction energies for these interactions were in
      the ranges 3.5-4.1 and 3.1-5.5 kJ mol-1 for polymorphs A and B, respectively, as
      shown by QTAIM analysis.

PMID- 29206119
TI  - Preparation and characterization of two new CuII supramolecular coordination
      polymers incorporating sulfobenzoate and flexible heterocyclic ligands.
AB  - The assembly of CuII with the multifunctional ligand 2-amino-4-sulfobenzoic acid
      (H2asba) in the presence of the auxiliary flexible ligands 1,4-bis(triazol-1
      ylmethyl)benzene (bbtz) and 1,4-bis(imidazol-1-ylmethyl)benzene (bix) under
      ambient conditions resulted in two new supramolecular coordination polymers,
      namely poly[[(3-amino-4-carboxybenzenesulfonato-kappaO)aquabis[MU2-1,4
      bis(triazol-1-ylmethyl)benzene-kappa2N4:N4']copper(II)] 3-amino-4
      carboxybenzenesulfonate tetrahydrate],
      {[Cu(C7H6NO5S)(C12H12N6)2(H2O)](C7H6NO5S).4H2O}n, (1), and poly[[bis(MU2-2-amino
      4-sulfonatobenzoato-kappa3O1:N,O1')tetraaqua[MU2-1,4-bis(triazol-1
      ylmethyl)benzene-kappa2N4:N4']dicopper(II)] tetrahydrate],
      {[Cu2(C7H5NO5S)2(C14H14N4)(H2O)4].4H2O}n, (2). Single-crystal X-ray structure
      diffraction analysis of (1) reveals that the bbtz ligand acts as a bridge,
      linking adjacent CuII ions into a two-dimensional cationic (4,4) topological
      network, in which the coordinated 3-amino-4-carboxybenzenesulfonate (Hasba-)
      anion uses its sulfonate group to bind with the CuII ion in a monodentate fashion
      and the carboxylate group remains protonated. The lattice Hasba- anion resides in
      the two-dimensional layer and balances the charge. The carboxylate group of the 2
      amino-4-sulfonatobenzoate (asba2-) ligand in (2) is involved in bidentate
      coordination, connecting adjacent CuII ions into carboxylate-bridged chains which
      are further bridged by the auxiliary flexible bix ligand in a trans-gauche (TG)
      mode, resulting in the formation of a two-dimensional network architecture. The
      amino group of the asba2- ligand in (2) also takes part in the coordination with
      the central CuII ion. The six-coordinated CuII centres in (1) and (2) exhibit
      distorted octahedral coordination geometries. Extensive hydrogen bonding exists
      in both (1) and (2). The interlayer hydrogen bonds in both compounds further
      extend adjacent two-dimensional layers into three-dimensional supramolecular
      network architectures. Furthermore, a detailed analysis of the solid-state UV-Vis
      NIR (NIR is near IR) diffuse reflectance data indicates that (1) and (2) may have
      potential as wide band gap indirect semiconductor materials. Compounds (1) and
      (2) show reversible and irreversible dehydration-rehydration behaviours,
      respectively.

PMID- 29206120
TI  - Syntheses and crystal structures of two heterometallic iodoplumbates containing
      mixed-valence copper(I/II).
AB  - Mixed-valence copper(I/II) atoms have been introduced successfully into a Pb/I
      skeleton to obtain two heterometallic iodoplumbates, namely poly[bis(tetra-n
      butylammonium) [bis(MU3-dimethyldithiocarbamato)dodeca-MU3-iodido-hexa-MU2-iodido
      tetracopper(I)copper(II)hexalead(II)]], {(C16H36N)2[Cu4ICuIIPb6(C3H6NS2)2I18]}n,
      (I), and poly[[MU3-iodido-tri-MU2-iodido-iodido[bis(1,10
      phenanthroline)copper(I)]copper(I)copper(II)lead(II)] hemiiodine],
      {[CuICuIIPbI5(C12H8N2)2].0.5I2}n, (II), under solution and solvothermal
      conditions, respectively. Compound (I) contains two-dimensional anionic layers,
      which are built upon the linkages of CuII(S2CNMe2)2 units and one-dimensional
      anionic Pb/I/CuI chains. Tetra-n-butylammonium cations are located between the
      anionic layers and connected to them via C-H...I hydrogen-bonding interactions.
      Compound (II) exhibits a one-dimensional neutral structure, which is composed of
      [PbI5] square pyramids, [CuII4] tetrahedra and [CuIIN4I] trigonal bipyramids.
      Face-to-face aromatic pi-pi stacking interactions between adjacent 1,10
      phenanthroline ligands stabilize the structure and assemble compound (II) into a
      three-dimensional supramolecular structure. I2 molecules lie in the voids of the
      structure.

PMID- 29206121
TI  - The march of progress: structures of the adducts of potassium dicyanidoaurate(I)
      with 2,2'-bipyridyl (redetermination) and 1,10-phenanthroline.
AB  - The structure of the 2,2'-bipyridyl adduct poly[(MU2-2,2'-bipyridyl
      kappa3N,N':N)di-MU3-cyanido-kappa6C:N:N-gold(I)potassium(I)],
      [AuK(CN)2(C10H8N2)]n, (1) (space group P21), has been redetermined [previous
      determination: Jones et al. (1980). Acta Cryst. B36, 160-162]. The bipyridyl
      ligands coordinate only the potassium ion, which has a coordination sphere
      consisting of seven N-atom donors; gold(I) remains in the form of linear
      dicyanidoaurate(I) ions. The extended structure consists of layers in which the
      AuI atoms form chains parallel to the short a axis, with Au...Au contacts of
      3.7286 (1) A, whereas the chains of potassium ions, which are also parallel to a,
      are bridged by bipyridyl and dicyanidoaurate residues. The analogous 1,10
      phenanthroline adduct, namely poly[di-MU3-cyanido-kappa6C:N:N-(MU2-1,10
      phenanthroline-kappa3N,N':N)gold(I)potassium(I)], [AuK(CN)2(C12H8N2)]n, (2),
      crystallizes as nonmerohedral twins in the space group C2/c. The packing is
      closely related to that of (1), but the chains are now parallel to the short b
      axis and the layers are parallel to (10?overline{1}). The two independent AuI
      atoms occupy special positions on inversion centres and twofold axes; the Au...Au
      contacts are 3.6771 (2) A.

PMID- 29206122
TI  - Synthesis of spiro[indoline-3,3'-pyrrolizines] by 1,3-dipolar reactions between
      isatins, L-proline and electron-deficient alkenes.
AB  - Two spiro[indoline-3,3'-pyrrolizine] derivatives have been synthesized in good
      yield with high regio- and stereospecificity using one-pot reactions between
      readily available starting materials, namely L-proline, substituted 1H-indole-2,3
      diones and electron-deficient alkenes. The products have been fully characterized
      by elemental analysis, IR and NMR spectroscopy, mass spectrometry and crystal
      structure analysis. In (1'RS,2'RS,3SR,7a'SR)-2'-benzoyl-1-hexyl-2-oxo
      1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-pyrrolizine]-1'-carboxylic acid,
      C28H32N2O4, (I), the unsubstituted pyrrole ring and the reduced spiro-fused
      pyrrole ring adopt half-chair and envelope conformations, respectively, while in
      (1'RS,2'RS,3SR,7a'SR)-1',2'-bis(4-chlorobenzoyl)-5,7-dichloro-2-oxo
      1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-pyrrolizine], which crystallizes
      as a partial dichloromethane solvate, C28H20Cl4N2O3.0.981CH2Cl2, (II), where the
      solvent component is disordered over three sets of atomic sites, these two rings
      adopt envelope and half-chair conformations, respectively. Molecules of (I) are
      linked by an O-H....O hydrogen bond to form cyclic R66(48) hexamers of
      ?overline{3} (S6) symmetry, which are further linked by two C-H...O hydrogen
      bonds to form a three-dimensional framework structure. In compound (II),
      inversion-related pairs of N-H...O hydrogen bonds link the spiro[indoline-3,3'
      pyrrolizine] molecules into simple R22(8) dimers.

PMID- 29206123
TI  - Polymorphs of the antiviral drug ganciclovir.
AB  - Ganciclovir (GCV; systematic name: 2-amino-9-{[(1,3-dihydroxypropan-2
      yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one), C9H13N5O4, an antiviral drug for
      treating cytomegalovirus infections, has two known polymorphs (Forms I and II),
      but only the structure of the metastable Form II has been reported [Kawamura &
      Hirayama (2009). X-ray Struct. Anal. Online, 25, 51-52]. We describe a successful
      preparation of GCV Form I and its crystal structure. GCV is an achiral molecule
      in the sense that its individual conformers, which are generally chiral objects,
      undergo fast interconversion in the liquid state and cannot be isolated. In the
      crystalline state, GCV exists as two inversion-related conformers in Form I and
      as a single chiral conformer in Form II. This situation is similar to that
      observed for glycine, also an achiral molecule, whose alpha-polymorph contains
      two inversion-related conformers, while the gamma-polymorph contains a single
      conformer that is chiral. The hydrogen bonds are exclusively intermolecular in
      Form I, but both inter- and intramolecular in Form II, which accounts for the
      different molecular conformations in the two polymorphs.

PMID- 29206124
TI  - Crystallographic and computational study of a network composed of [ZnCl4]2-
      anions and triply protonated 4'-functionalized terpyridine cations.
AB  - We report herein the synthesis, crystallographic analysis and a study of the
      noncovalent interactions observed in the new 4'-substituted terpyridine-based
      derivative bis[4'-(isoquinolin-2-ium-4-yl)-2,2':6',2''-terpyridine-1,1''-diium]
      tris[tetrachloridozincate(II)] monohydrate, (C24H19N4)2[ZnCl4]3.H2O or
      (ITPH3)2[ZnCl4]3.H2O, where (ITPH3)3+ is the triply protonated cation derived
      from 4'-(isoquinolin-4-yl)-2,2':6',2''-terpyridine (ITP) [Granifo et al. (2016).
      Acta Cryst. C72, 932-938]. The (ITPH3)3+ cation presents a number of interesting
      similarities and differences compared with its neutral ITP relative, mainly in
      the role fulfilled in the packing arrangement by the profuse set of D-H...A [D
      (donor) = C, N or O; A (acceptor) = O or Cl], pi-pi and anion...pi noncovalent
      interactions present. We discuss these interactions in two different
      complementary ways, viz. using a point-to-point approach in the light of Bader's
      theory of Atoms In Molecules (AIM), analyzing the individual significance of each
      interaction, and in a more 'global' analysis, making use of the Hirshfeld
      surfaces and the associated enrichment ratio (ER) approach, evaluating the
      surprisingly large co-operative effect of the superabundant weaker contacts.

PMID- 29206125
TI  - Dimerization of a mixed-carbene PdII dibromide complex by elemental iodine.
AB  - A monomeric PdII complex bearing a mixed carbocyclic/N-heterocyclic carbene
      ligand and two bromides was reacted with an excess of elemental iodine, which
      resulted in the surprising removal of one bromide ligand and dimerization of the
      mixed-carbene complex to form di-MU-bromido-bis{[1-(cyclohepta-2,4,6-trien-2-yl-1
      ylidene-kappaC1)-3-(2,6-diisopropylphenyl)imidazol-2-ylidene]palladium(II)}
      bis(pentaiodide) dichloromethane monosolvate, [Pd2Br2(C22H24N2)2](I5)2.CH2Cl2.
      The dimeric complex features a slightly distorted square-planar core of two PdII
      centres bridged by two bromide ligands, which lie in the same plane as the seven-
      and five-membered rings of the bidentate carbene ligand. The counter-ions in the
      single crystal were found to be pentaiodide monoanions featuring their typical V
      shape, whereas for the bulk material, a mixture of Br/I interhalides is proposed.

PMID- 29206126
TI  - A combined crystallographic, thermal, Raman and computational study on
      polymorphism and phase transition in 1-(4-hexyloxy-3-hydroxyphenyl)ethanone.
AB  - The crystal structure of the triclinic polymorph of 1-(4-hexyloxy-3
      hydroxyphenyl)ethanone, C14H20O3, differs markedly from that of the orthorhombic
      polymorph [Manzano et al. (2015). Acta Cryst. C71, 1022-1027]. The two molecular
      structures are alike with respect to their bond lengths and angles, but differ in
      their spatial arrangement. This gives rise to quite different packing schemes,
      even if built up by similar chains having the hydroxy-ethanone O-H...O hydrogen
      bond synthon in common. Both phases were found to be related by a first-order
      thermally driven phase transformation at 338-340 K, which is discussed in detail.
      The relative stabilities of both polymorphs are explained on the basis of both
      the noncovalent interactions operating in each structure and quantum chemical
      calculations. The polymorphic phase transition has also been studied
      experimentally by means of differential scanning calorimetry (DSC) experiments,
      conducted on individual single crystals, Raman spectroscopy and controlled
      heating under a microscope of individual single crystals, which were further
      characterized by powder and single-crystal X-ray diffraction.

PMID- 29206127
TI  - New fluorescent compounds based on zinc thiocyanate: influence of structure on
      spectral properties.
AB  - New coordination compounds based on zinc thiocyanate, namely (acetone
      thiosemicarbazone-kappa2N1,S)bis(isothiocyanato-kappaN)zinc(II) monohydrate,
      [Zn(NCS)2(C4H9N3S)].H2O, (I), and diaquatetrakis(urea-kappaO)zinc(II)
      tetrakis(isothiocyanato-kappaN)zinc(II), [Zn(CH4N2O)4(H2O)2][Zn(NCS)4], (II),
      were synthesized and studied by UV-Vis, fluorescence and IR spectroscopy.
      Coordination salt (II) forms a rare system composed of two different coordination
      units of the same metal and it is the first example of a compound with two
      completely different zinc coordination units, of which one contains a
      tetrakis(urea)zinc unit. Both (I) and (II) possess fluorescence properties and
      produce blue and green emissions, respectively, upon irradiation with violet
      light. The spectral properties were correlated with the observed molecular and
      supramolecular structures. The acetone thiosemicarbazone ligand of (I) exhibits
      (upon coordination) red shifts of bands corresponding to N=C and C=S stretching
      vibration frequencies, which is not typical for chelating molecules.

PMID- 29206128
TI  - Conformational study of (Z)-5-(4-chlorobenzylidene)-2-[4-(2
      hydroxyethyl)piperazin-1-yl]-3H-imidazol-4(5H)-one in different environments:
      insight into the structural properties of bacterial efflux pump inhibitors.
AB  - The 2-amine derivatives of 5-arylidene-3H-imidazol-4(5H)-one are a new class of
      bacterial efflux pump inhibitors, the chemical compounds that are able to restore
      antibiotic efficacy against multidrug resistant bacteria. 5-Arylidene-3H-imidazol
      4(5H)-ones with a piperazine ring at position 2 reverse the mechanisms of
      multidrug resistance (MDR) of the particularly dangerous Gram-negative bacteria
      E. coli by inhibition of the efflux pump AcrA/AcrB/TolC (a main multidrug
      resistance mechanism in Gram-negative bacteria, consisting of a membrane fusion
      protein, AcrA, a Resistant-Nodulation-Division protein, AcrB, and an outer
      membrane factor, TolC). In order to study the influence of the environment on the
      conformation of (Z)-5-(4-chlorobenzylidene)-2-[4-(2-hydroxyethyl)piperazin-1-yl]
      3H-imidazol-4(5H)-one, (3), two different salts were prepared, namely with
      picolinic acid {systematic name: 4-[(Z)-4-(4-chlorobenzylidene)-5-oxo-3,4-dihydro
      1H-imidazol-2-yl]-1-(2-hydroxyethyl)piperazin-1-ium pyridine-2-carboxylate,
      C16H20ClN4O2+.C6H4NO2-, (3a)} and 4-nitrophenylacetic acid {systematic name: 4
      [(Z)-4-(4-chlorobenzylidene)-5-oxo-3,4-dihydro-1H-imidazol-2-yl]-1-(2
      hydroxyethyl)piperazin-1-ium 2-(4-nitrophenyl)acetate, C16H20ClN4O2+.C8H6NO4-,
      (3b)}. The crystal structures of the new salts were determined by X-ray
      diffraction. In both crystal structures, the molecule of (3) is protonated at an
      N atom of the piperazine ring by proton transfer from the corresponding acid. The
      carboxylate group of picolinate engages in hydrogen bonds with three molecules of
      the cation of (3), whereas the carboxylate group of 4-nitrophenylacetate engages
      in hydrogen bonds with only two molecules of (3). As a consequence of these
      interactions, different orientations of the hydroxyethyl group of (3) are
      observed. The crystal structures are additionally stabilized by both C-H...N [in
      (3a)] and C-H...O [in (3a) and (3b)] intermolecular interactions. The geometry of
      the imidazolone fragment was compared with other crystal structures possessing
      this moiety. The tautomer observed in the crystal structures presented here,
      namely 3H-imidazol-4(5H)-one [systematic name: 1H-imidazol-5(4H)-one], is also
      that most frequently observed in other structures containing this heterocycle.

PMID- 29206131
TI  - Influence of Maternal Care on Behavioural Development of Domestic Dogs (Canis
      Familiaris) Living in a Home Environment.
AB  - Maternal care has been shown to affect the development of the brain, behaviour,
      social skills and emotional systems of the young of many mammalian species
      including dogs. The aim of the present study was to determine the effects of
      maternal care on the behavioural responses of family dog puppies towards
      environmental and social stimuli. In order to do this, maternal care (licking
      puppy's ano-genital area, licking the puppy, nursing and mother-puppy contact)
      during the first three weeks after birth was assessed in 12 litters of domestic
      dog puppies reared in home environments (total = 72 puppies). The behavioural
      responses of puppies were assessed in an arena and an isolation test, which were
      performed when the puppies were two-month old. Data were analysed using principal
      components analysis and projection to latent structures regression. A systematic
      relationship was found between maternal care and behaviour in both tests. In the
      arena test, maternal care was found to be positively associated with approach to
      the stranger, attention oriented to the stranger, time spent near the enclosure,
      yawning, whining and yelping (R2Y = 0.613, p = 8.2 * 10-9). Amount of maternal
      care was negatively associated with the number of squares crossed and the time
      spent individually playing with the rope. In the isolation test, the amount of
      maternal care was positively associated with standing posture, paw lifting, and
      howling, and it was negatively associated with yawning, lying down and nose
      licking (R2Y = 0.507, p = 0.000626). These results suggest that the amount of
      maternal care received during early life influences the pattern of behavioural
      responses and coping strategies of puppies at two-months of age. On the basis of
      these findings it could be speculated that early maternal care contributes to
      adaption to the environment in which family puppies are developing, with
      particular regard to social relationships with people.

PMID- 29206132
TI  - Effect of Grazing Behavior on Weight Regain Post-Bariatric Surgery: A Systematic
      Review.
AB  - Grazing, a type of maladaptive eating behavior, has been associated with poor
      weight outcomes in bariatric patients. The purpose of this study was to conduct a
      systematic review of the association between grazing behavior and weight regain
      post-bariatric surgery. Literature searches, study selection, design of the
      method, and quality appraisal were carried out by two independent authors. The
      search strategy was performed until October 2017 in Medline, Embase, Cochrane,
      Lilacs, Scopus, Web of Science, Google Scholar, ProQuest Dissertation & Theses,
      and Open Grey. Of a total of 3764 articles, five papers met the inclusion
      criteria (four original articles and one thesis), comprising 994 subjects, mostly
      women. The prevalence of grazing behavior ranged from 16.6 to 46.6%, and the
      highest prevalence of significant weight regain was 47%. The association between
      grazing and weight regain was observed in four of the five evaluated studies. Our
      findings support an association between grazing behavior and weight regain after
      bariatric surgery, regardless of surgery type and contextual concept of grazing.
      Further studies are needed to confirm the clarity of the real prevalence and
      interfering factors related to grazing behavior and weight outcomes.

PMID- 29206133
TI  - Gas Leak Detection by Dilution of Atmospheric Oxygen.
AB  - Gas leak detection is an important issue in infrastructure monitoring and
      industrial production. In this context, infrared (IR) absorption spectroscopy is
      a major measurement method. It can be applied in an extractive or remote
      detection scheme. Tunable laser spectroscopy (TLS) instruments are able to detect
      CH4 leaks with column densities below 10 ppm.m from a distance of 30 m in less
      than a second. However, leak detection of non-IR absorbing gases such as N2 is
      not possible in this manner. Due to the fact that any leaking gas displaces or
      dilutes the surrounding background gas, an indirect detection is still possible.
      It is shown by sensitive TLS measurements of the ambient background concentration
      of O2 that N2 leaks can be localized with extractive and standoff methods for
      distances below 1 m. Minimum leak rates of 0.1 mbar.L/s were determined. Flow
      simulations confirm that the leakage gas typically effuses in a narrow jet. The
      sensitivity is mainly determined by ambient flow conditions. Compared to TLS
      detection of CH4 at 1651 nm, the indirect method using O2 at 761 nm is
      experimentally found to be less sensitive by a factor of 100. However, the well
      established TLS of O2 may become a universal tool for rapid leakage screening of
      vessels that contain unknown or inexpensive gases, such as N2.

PMID- 29206130
TI  - The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine
      Asthma.
AB  - Aging is associated with a dysregulation of the immune system, leading to a
      general pro-inflammatory state of the organism, a process that has been named
      inflamm-aging. Oxidative stress has an important role in aging and in the
      regulation of immune responses, probably playing a role in the development of age
      related diseases. The respiratory system function physiologically declines with
      the advancement of age. In elderly asthmatic patients, this may contribute to
      disease expression. In this review, we will focus on age-related changes
      affecting the immune system and in respiratory structure and function that could
      contribute to asthma occurrence, and/or clinical presentation in the elderly.
      Also, naturally occurring equine asthma will be discussed as a possible model for
      studying the importance of oxidative stress and immun-aging/inflamm-aging in
      humans.

PMID- 29206134
TI  - Variable Isotopic Compositions of Host Plant Populations Preclude Assessment of
      Aphid Overwintering Sites.
AB  - Soybean aphid (Aphis glycines Matsumura) is a pest of soybean in the northern
      Midwest whose migratory patterns have been difficult to quantify. Improved
      knowledge of soybean aphid overwintering sites could facilitate the development
      of control efforts with exponential impacts on aphid densities on a regional
      scale. In this preliminary study, we explored the utility of variation in stable
      isotopes of carbon and nitrogen to distinguish soybean aphid overwintering
      origins. We compared variation in bulk 13C and 15N content in buckthorn (Rhamnus
      cathartica L.) and soybean aphids in Wisconsin, among known overwintering
      locations in the northern Midwest. Specifically, we looked for associations
      between buckthorn and environmental variables that could aid in identifying
      overwintering habitats. We detected significant evidence of correlation between
      the bulk 13C and 15N signals of soybean aphids and buckthorn, despite high
      variability in stable isotope composition within and among buckthorn plants.
      Further, the 15N signal in buckthorn varied predictably with soil composition.
      However, lack of sufficient differentiation of geographic areas along axes of
      isotopic and environmental variation appears to preclude the use of carbon and
      nitrogen isotopic signals as effective predictors of likely aphid overwintering
      sites. These preliminary data suggest the need for future work that can further
      account for variability in 13C and 15N within/among buckthorn plants, and that
      explores the utility of other stable isotopes in assessing likely aphid
      overwintering sites.

PMID- 29206135
TI  - Ethanol (E) Impairs Fetal Brain GSH Homeostasis by Inhibiting Excitatory Amino
      Acid Carrier 1 (EAAC1)-Mediated Cysteine Transport.
AB  - Central among the fetotoxic responses to in utero ethanol (E) exposure is redox
      shift related glutathione (GSH) loss and apoptosis. Previously, we reported that
      despite an E-generated Nrf2 upregulation, fetal neurons still succumb. In this
      study, we investigate if the compromised GSH results from an impaired inward
      transport of cysteine (Cys), a precursor of GSH in association with dysregulated
      excitatory amino acid carrier1 (EAAC1), a cysteine transporter. In utero binge
      model involves administration of isocaloric dextrose or 20% E (3.5 g/kg)/ by
      gavage at 12 h intervals to pregnant Sprague Dawley (SD) rats, starting gestation
      day (gd) 17 with a final dose on gd19, 2 h prior to sacrifice. Primary cerebral
      cortical neurons (PCNs) from embryonic day 16-17 fetal SD rats were the in vitro
      model. E reduced both PCN and cerebral cortical GSH and Cys up to 50% and the
      abridged GSH could be blocked by administration of N-acetylcysteine. E reduced
      EAAC1 protein expression in utero and in PCNs (p < 0.05). This was accompanied by
      a 60-70% decrease in neuron surface expression of EAAC1 along with significant
      reductions of EAAC1/Slc1a1 mRNA (p < 0.05). In PCNs, EAAC1 knockdown
      significantly decreased GSH but not oxidized glutathione (GSSG) illustrating that
      while not the sole provider of Cys, EAAC1 plays an important role in neuron GSH
      homeostasis. These studies strongly support the concept that in both E exposed
      intact fetal brain and cultured PCNs a mechanism underlying E impairment of GSH
      homeostasis is reduction of import of external Cys which is mediated by
      perturbations of EAAC1 expression/function.

PMID- 29206137
TI  - Analysis of Fresnel Zone Plates Focusing Dependence on Operating Frequency.
AB  - The focusing properties of Fresnel Zone Plates (FZPs) against frequency are
      analyzed in this work. It is shown that the FZP focal length depends almost
      linearly on the operating frequency. Focal depth and focal distortion are also
      considered, establishing a limit on the frequency span at which the operating
      frequency can be shifted. An underwater FZP ultrasound focusing system is
      demonstrated, and experimental results agree with the theoretical analysis and
      simulations.

PMID- 29206136
TI  - The Effects of Phytosterols Extracted from Diascorea alata on the Antioxidant
      Activity, Plasma Lipids, and Hematological Profiles in Taiwanese Menopausal
      Women.
AB  - The efficacy of phytosterols extracted from Diascorea alata on antioxidant
      activities, plasma lipids and hematological profiles was assessed in
      postmenopausal women. Gas chromatography and mass spectrophotometry was employed
      to determine the steroid content of Taiwanese yam (Diascorea alata cv. Tainung
      No. 2). A two-center, randomized, double-blind, placebo-controlled clinical
      investigation on 50 postmenopausal women randomly assigned to two groups treated
      for 12 months with placebo or two sachets daily of Diascorea extracts containing
      12 mg/dose was carried out. The main outcome measures were the plasma antioxidant
      activities, hematological profiles, and the concentrations of plasma lipids,
      including cholesterol, triglyceride, low density lipoprotein, high density
      lipoprotein, very low density lipoprotein,, and apolipoprotein A1 and B. A one
      way analysis of covariance (ANCOVA) test was performed to investigate the
      significance. Beta-sitosterol, stigmasterol, 22-23-dihydro-, and gamma-sitosterol
      were major phytosterols determined from Diascorea extracts. At six months in
      those receiving Diascorea, there were significantly decreased leukocyte counts (p
      < 0.01) and improvement on antioxidant activity of malondialdehyde (p < 0.001).
      After 12 months' treatment, elevations of hematocrit and mean corpuscular volume
      (p < 0.01) were noted in those receiving Diascorea. Moreover, the low dose
      Diascorea consumption in menopausal women for one year generally did not present
      positive effects on lipid profiles.

PMID- 29206138
TI  - Intratubular Biomineralization in a Root Canal Filled with Calcium-Enriched
      Material over 8 Years.
AB  - This case report describes intratubular biomineralization in root canal, filled
      with calcium-enriched material after 8 years of clinical maintenance. The
      schematic findings of dentinal tubules were investigated with scanning electron
      microscopy (SEM) and energy dispersive spectroscopy (EDS). The root canal
      obturation material was closely adapted to root dentin surface, suggesting the
      possibility of chemical bonding between the two interfaces. SEM and EDS
      observation of dentinal tubules showed intratubular biomineralized crystal
      structures with Ca/P ratio in a range of 1.30-2.12, suggesting bioactive capacity
      of calcium-enriched material.

PMID- 29206139
TI  - Alkaline Materials and Regenerative Endodontics: A Review.
AB  - Periapical health is the primary goal of endodontic treatment in mature and
      immature teeth. In addition, the goals of treatment of immature teeth with
      arrested root development include root growth to length and maturation of the
      apex, as well as thickening of the canal wall. These goals are valid for immature
      teeth that have been subjected to trauma and dental caries or that are the result
      of developmental anomalies that expose the tooth to the risk of pulp necrosis and
      consequently result in the cessation of root maturation. Regenerative endodontic
      procedures (REPs) have been described as a "paradigm shift" in the treatment of
      immature teeth with pulp necrosis and underdeveloped roots, as there is the
      potential for further root maturation and return of vitality. Treatment with REPs
      is advocated as the treatment of choice for immature teeth with pulp necrosis.
      REP protocols involve the use of alkaline biomaterials, primarily sodium
      hypochlorite, calcium hydroxide, mineral trioxide aggregates and Biodentine, and
      are the essential components of a successful treatment regimen.

PMID- 29206140
TI  - Surfactant Effects on Structure and Mechanical Properties of Ultrahigh-Molecular
      Weight Polyethylene/Layered Silicate Composites.
AB  - In this study, the reinforcement of ultrahigh-molecular-weight polyethylene
      (UHMWPE) with biotite was investigated. The biotite filler was mechanically
      activated with different dry surfactants to improve its compatibility with UHMWPE
      and decrease agglomeration among biotite particles. Alkyldimethylbenzylammonium
      chloride (ADBAC) and cetyltrimethylammonium bromide (CTAB) were selected as
      cationic surfactants. The tensile strength of composites containing 1 wt % of
      CTAB-treated biotite was increased by 30% relative to those with untreated
      biotite, but was unchanged with ADBAC treatment of the same biotite content. The
      stereochemistry of the surfactant may be critical to the composite structure and
      mechanical properties of the material. The stereochemistry of CTAB was preferable
      to that of ADBAC in enhancing mechanical properties because the stereochemistry
      of ADBAC impedes favorable interactions with the biotite surface during
      mechanical activation.

PMID- 29206141
TI  - (-)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium
      falciparum Hsp70 Chaperones and Abrogates Their Association with Functional
      Partners.
AB  - Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly
      as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70
      family of proteins represents one of the most important molecular chaperones in
      the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70
      isoforms. Two (PfHsp70-1 and PfHsp70-z) of these localize to the parasite
      cytosol. PHsp70-1 is known to occur in a functional complex with another
      chaperone, PfHsp90 via a co-chaperone, P. falciparum Hsp70-Hsp90 organising
      protein (PfHop). (-)-Epigallocatechin-3-gallate (EGCG) is a green tea constituent
      that is thought to possess antiplasmodial activity. However, the mechanism by
      which EGCG exhibits antiplasmodial activity is not fully understood. A previous
      study proposed that EGCG binds to the N-terminal ATPase domain of Hsp70. In the
      current study, we overexpressed and purified recombinant forms of two P.
      falciparum cytosol localized Hsp70s (PfHsp70-1 and PfHsp70-z), and PfHop, a co
      chaperone of PfHsp70-1. Using the surface plasmon resonance approach, we
      demonstrated that EGCG directly binds to the two Hsp70s. We further observed that
      binding of EGCG to the two proteins resulted in secondary and tertiary
      conformational changes. In addition, EGCG inhibited the ATPase and chaperone
      function of the two proteins. Furthermore, EGCG abrogated association of the two
      Hsp70s with their functional partners. Using parasites cultured in vitro at the
      blood stages, we observed that 2.9 uM EGCG suppressed 50% P. falciparum parasite
      growth (IC50). Our findings demonstrate that EGCG directly binds to PfHsp70-1 and
      PfHsp70-z to inhibit both the ATPase and chaperone functions of the proteins. Our
      study constitutes the first direct evidence suggesting that the antiplasmodial
      activity of EGCG is at least in part accounted for by its inhibition of Hsp70
      function.

PMID- 29206142
TI  - Composition and Antibacterial Activity of the Essential Oils of Orthosiphon
      stamineus Benth and Ficus deltoidea Jack against Pathogenic Oral Bacteria.
AB  - In this study, the essential oils of Orthosiphon stamineus Benth and Ficus
      deltoidea Jack were evaluated for their antibacterial activity against invasive
      oral pathogens, namely Enterococcus faecalis, Streptococcus mutans, Streptococcus
      mitis, Streptococcus salivarius, Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis and Fusobacterium nucleatum. Chemical composition of the
      oils was analyzed using gas chromatography (GC) and gas chromatography-mass
      spectrometry (GC-MS). The antibacterial activity of the oils and their major
      constituents were investigated using the broth microdilution method (minimal
      inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)).
      Susceptibility test, anti-adhesion, anti-biofilm, checkerboard and time-kill
      assays were also carried out. Physiological changes of the bacterial cells after
      exposure to the oils were observed under the field emission scanning electron
      microscope (FESEM). O. stamineus and F. deltoidea oils mainly consisted of
      sesquiterpenoids (44.6% and 60.9%, respectively), and beta-caryophyllene was the
      most abundant compound in both oils (26.3% and 36.3%, respectively). Other
      compounds present in O. stamineus were alpha-humulene (5.1%) and eugenol (8.1%),
      while alpha-humulene (5.5%) and germacrene D (7.7%) were dominant in F.
      deltoidea. The oils of both plants showed moderate to strong inhibition against
      all tested bacteria with MIC and MBC values ranging 0.63-2.5 mg/mL. However, none
      showed any inhibition on monospecies biofilms. The time-kill assay showed that
      combination of both oils with amoxicillin at concentrations of 1* and 2* MIC
      values demonstrated additive antibacterial effect. The FESEM study showed that
      both oils produced significant alterations on the cells of Gram-negative bacteria
      as they became pleomorphic and lysed. In conclusion, the study indicated that the
      oils of O. stamineus and F. deltoidea possessed moderate to strong antibacterial
      properties against the seven strains pathogenic oral bacteria and may have caused
      disturbances of membrane structure or cell wall of the bacteria.

PMID- 29206144
TI  - New Type of Halogen Bond: Multivalent Halogen Interacting with pi- and sigma
      Electrons.
AB  - MP2/aug-cc-pVTZ calculations were performed for complexes of BrF3 and BrF5 acting
      as Lewis acids through the bromine centre, with species playing a role of Lewis
      base: dihydrogen, acetylene, ethylene, and benzene. The molecular hydrogen
      donates electrons by its sigma-bond, while in remaining moieties-in complexes of
      hydrocarbons; such an electron transfer follows from pi-electrons. The complexes
      are linked by a kind of the halogen bond that is analyzed for the first time in
      this study, i.e., it is the link between the multivalent halogen and pi or sigma
      electrons. The nature of such a halogen bond is discussed, as well as various
      dependencies and correlations are presented. Different approaches are applied
      here, the Quantum Theory of Atoms in Molecules, Natural Bond Orbital method, the
      decomposition of the energy of interaction, the analysis of electrostatic
      potentials, etc.

PMID- 29206143
TI  - Lipoprotein Lipase Expression in Chronic Lymphocytic Leukemia: New Insights into
      Leukemic Progression.
AB  - Lipoprotein lipase (LPL) is a central enzyme in lipid metabolism. Due to its
      catalytic activity, LPL is involved in metabolic pathways exploited by various
      solid and hematologic malignancies to provide an extra energy source to the tumor
      cell. We and others described a link between the expression of LPL in the tumor
      cell and a poor clinical outcome of patients suffering Chronic Lymphocytic
      Leukemia (CLL). This leukemia is characterized by a slow accumulation of mainly
      quiescent clonal CD5 positive B cells that infiltrates secondary lymphoid organs,
      bone marrow and peripheral blood. Despite LPL being found to be a reliable
      molecular marker for CLL prognosis, its functional role and the molecular
      mechanisms regulating its expression are still matter of debate. Herein we
      address some of these questions reviewing the current state of the art of LPL
      research in CLL and providing some insights into where currently unexplored
      questions may lead to.

PMID- 29206145
TI  - Dual-Wavelength Laser Speckle Contrast Imaging (dwLSCI) Improves Chronic
      Measurement of Superficial Blood Flow in Hands.
AB  - Laser speckle contrast imaging (LSCI) has been widely used to determine blood
      flow and perfusion in biological tissues. The physical model of traditional LSCI
      ignores the effects of scattering property distribution in relation to speckle
      correlation time tauc and blood flow v, which further results in biased
      estimation. In this study, we developed a dual-wavelength laser speckle contrast
      imaging (dwLSCI) method and a portable device for imaging the blood flow and
      tissue perfusion in human hands. Experimental data showed that dwLSCI could
      retrieve the vein vasculatures under the surface skin, and it further provided
      accurate measurements of vein blood flow signals, tissue perfusion signals, and
      fingertip perfusion signals, which assist with assessments of rehabilitation
      therapy for stroke patients. Fingertip perfusion signals demonstrated better
      performance in early assessments, while vein blood flow signals assisted the Fugl
      Meyer Assessment Scale (FMA) and the Wolf Motor Function Test (WMFT) behavior
      assessments. As a general noninvasive imaging method, dwLSCI can be applied in
      clinical studies related to hand functions combined with behavior assessments.

PMID- 29206146
TI  - Thermally and Electrically Conductive Nanopapers from Reduced Graphene Oxide:
      Effect of Nanoflakes Thermal Annealing on the Film Structure and Properties.
AB  - In this study, we report a novel strategy to prepare graphene nanopapers from
      direct vacuum filtration. Instead of the conventional method, i.e., thermal
      annealing nanopapers at extremely high temperatures prepared from graphene oxide
      (GO) or partially reduced GO, we fabricate our graphene nanopapers directly from
      suspensions of fully reduced graphene oxide (RGO), obtained after RGO and thermal
      annealing at 1700  degrees C in vacuum. By using this approach, we studied the
      effect of thermal annealing on the physical properties of the macroscopic
      graphene-based papers. Indeed, we demonstrated that the enhancement of the
      thermal and electrical properties of graphene nanopapers prepared from annealed
      RGO is strongly influenced by the absence of oxygen functionalities and the
      morphology of the nanoflakes. Hence, our methodology can be considered as a valid
      alternative to the classical approach.

PMID- 29206147
TI  - Phloem-Conducting Cells in Haustoria of the Root-Parasitic Plant Phelipanche
      aegyptiaca Retain Nuclei and Are Not Mature Sieve Elements.
AB  - Phelipanche aegyptiaca parasitizes a wide range of plants, including important
      crops, and causes serious damage to their production. P. aegyptiaca develops a
      specialized intrusive organ called a haustorium that establishes connections to
      the host's xylem and phloem. In parallel with the development of xylem vessels,
      the differentiation of phloem-conducting cells has been demonstrated by the
      translocation of symplasmic tracers from the host to the parasite. However, it is
      unclear yet whether haustorial phloem-conducting cells are sieve elements. In
      this study, we identified phloem-conducting cells in haustoria by the host-to
      parasite translocation of green fluorescent protein (GFP) from AtSUC2pro::GFP
      tomato sieve tubes. Haustorial GFP-conducting cells contained nuclei but not
      callose-rich sieve plates, indicating that phloem-conducting cells in haustoria
      differ from conventional sieve elements. To ascertain why the nuclei were not
      degenerated, expression of the P. aegyptiaca homologs NAC-domain containing
      transcription factor (NAC45), NAC45/86-dependent exonuclease-domain protein 1
      (NEN1), and NEN4 was examined. However, these genes were more highly expressed in
      the haustorium than in tubercle protrusion, implying that nuclear degradation in
      haustoria may not be exclusively controlled by the NAC45/86-NEN regulatory
      pathway. Our results also suggest that the formation of plasmodesmata with large
      size exclusion limits is independent of nuclear degradation and callose
      deposition.

PMID- 29206148
TI  - A Comparative Study of Coupled Preferential Crystallizers for the Efficient
      Resolution of Conglomerate-Forming Enantiomers.
AB  - The separation of enantiomers is of great importance due to their possible
      differences in therapeutic properties. Preferential crystallization in various
      configurations of coupled batch crystallizers is used as an attractive means to
      separate the conglomerate-forming enantiomers from racemic mixtures. However, the
      productivity of such batch processes can be limited by the nucleation of the
      counter enantiomer and consumption of the supersaturation. In this work, a
      recently proposed process configuration, which uses coupled mixed suspension
      mixed product removal (MSMPR) with liquid phase exchange, is investigated by
      simulation studies. A detailed study on the effect of process parameters (e.g.,
      feed flow rate, seed mass, and liquid phase exchange) on the productivity and
      yield of the coupled MSMPR has been presented. Moreover, a comparison of various
      coupled crystallizer configurations is carried out. It is shown through
      simulation studies that the productivity of the enantiomeric separation can be
      significantly improved compared to the previously proposed batch modes when the
      continuous configuration is used. The effect of nucleation kinetic parameters on
      the performances of various crystallizer configurations is studied as well. A set
      of coupled population balance equations (PBEs) was used to describe the evolution
      of the crystal phase of the both enantiomers in each vessel. These equations were
      solved numerically using the quadrature method of moments. The insights obtained
      in this study will be useful in the process design of coupled crystallizer
      systems.

PMID- 29206149
TI  - Real-Time and In-Flow Sensing Using a High Sensitivity Porous Silicon Microcavity
      Based Sensor.
AB  - Porous silicon seems to be an appropriate material platform for the development
      of high-sensitivity and low-cost optical sensors, as their porous nature
      increases the interaction with the target substances, and their fabrication
      process is very simple and inexpensive. In this paper, we present the
      experimental development of a porous silicon microcavity sensor and its use for
      real-time in-flow sensing application. A high-sensitivity configuration was
      designed and then fabricated, by electrochemically etching a silicon wafer.
      Refractive index sensing experiments were realized by flowing several dilutions
      with decreasing refractive indices, and measuring the spectral shift in real
      time. The porous silicon microcavity sensor showed a very linear response over a
      wide refractive index range, with a sensitivity around 1000 nm/refractive index
      unit (RIU), which allowed us to directly detect refractive index variations in
      the 10-7 RIU range.

PMID- 29206150
TI  - Dynamic Modelling of Embeddable Piezoceramic Transducers.
AB  - Embedded Lead Zirconate Titanate (PZT) transducers have been widely used in
      research related to monitoring the health status of concrete structures. This
      paper presents a dynamic model of an embeddable PZT transducer with a waterproof
      layer and a protecting layer. The proposed model is verified by finite-element
      method (FEM). Based on the proposed model, the factors influencing the dynamic
      property of the embeddable PZT transducers, which include the material and
      thickness of the protecting layer, the material and thickness of the waterproof
      layer, and the thickness of the PZT, are analyzed. These analyses are further
      validated by a series of dynamic stress transfer experiments on embeddable PZT
      transducers. The results show that the excitation frequency can significantly
      affect the stress transfer of the PZT transducer in terms of both amplitude and
      signal phase. The natural frequency in the poling direction for the PZT
      transducer is affected by the material properties and the thickness of the
      waterproof and protecting layers. The studies in this paper will provide a
      scientific basis to design embeddable PZT transducers with special functions.

PMID- 29206151
TI  - An Overview of l-Amino Acid Oxidase Functions from Bacteria to Mammals: Focus on
      the Immunoregulatory Phenylalanine Oxidase IL4I1.
AB  - l-amino acid oxidases are flavin adenine dinucleotide-dependent enzymes present
      in all major kingdom of life, from bacteria to mammals. They participate in
      defense mechanisms by limiting the growth of most bacteria and parasites. A few
      mammalian LAAOs have been described, of which the enzyme "interleukin-4 induced
      gene 1" (IL4I1) is the best characterized. IL4I1 mainly oxidizes l-phenylalanine.
      It is a secreted enzyme physiologically produced by antigen presenting cells of
      the myeloid and B cell lineages and T helper type (Th) 17 cells. Important roles
      of IL4I1 in the fine control of the adaptive immune response in mice and humans
      have emerged during the last few years. Indeed, IL4I1 inhibits T cell
      proliferation and cytokine production and facilitates naive CD4+ T-cell
      differentiation into regulatory T cells in vitro by limiting the capacity of T
      lymphocytes to respond to clonal receptor stimulation. It may also play a role in
      controlling the germinal center reaction for antibody production and limiting Th1
      and Th17 responses. IL4I1 is expressed in tumor-associated macrophages of most
      human cancers and in some tumor cell types. Such expression, associated with its
      capacity to facilitate tumor growth by inhibiting the anti-tumor T-cell response,
      makes IL4I1 a new potential druggable target in the field of immunomodulation in
      cancer.

PMID- 29206152
TI  - Connecting the Mind-Body Split: Understanding the Relationship between Symptoms
      and Emotional Well-Being in Chronic Pain and Functional Gastrointestinal
      Disorders.
AB  - Paediatric chronic conditions, e.g., chronic pain and functional gastrointestinal
      disorders, are commonly diagnosed, with fatigue, pain and abdominal discomfort
      the most frequently reported symptoms across conditions. Regardless of whether
      symptoms are connected to an underlying medical diagnosis or not, they are often
      associated with an increased experience of psychological distress by both the ill
      child and their parents. While pain and embarrassing symptoms can induce
      increased distress, evidence is also accumulating in support of a reciprocal
      relationship between pain and distress. This reciprocal relationship is nicely
      illustrated in the fear avoidance model of pain, which has recently been found to
      be applicable to childhood pain experiences. The purpose of this article is to
      illustrate how mind (i.e., emotions) and body (i.e., physical symptoms) interact
      using chronic pain and gastrointestinal disorders as key examples. Despite the
      evidence for the connection between mind and body, the mind-body split is still a
      dominant position for families and health care systems, as evidenced by the
      artificial split between physical and mental health care. In a mission to
      overcome this gap, this article will conclude by providing tools on how the
      highlighted evidence can help to close this gap between mind and body.

PMID- 29206153
TI  - Is Genetic Mobilization Considered When Using Bacteriophages in Antimicrobial
      Therapy?
AB  - The emergence of multi-drug resistant bacteria has undermined our capacity to
      control bacterial infectious diseases. Measures needed to tackle this problem
      include controlling the spread of antibiotic resistance, designing new
      antibiotics, and encouraging the use of alternative therapies. Phage therapy
      seems to be a feasible alternative to antibiotics, although there are still some
      concerns and legal issues to overcome before it can be implemented on a large
      scale. Here we highlight some of those concerns, especially those related to the
      ability of bacteriophages to transport bacterial DNA and, in particular,
      antibiotic resistance genes.

PMID- 29206154
TI  - Application of a Saddle-Type Eddy Current Sensor in Steel Ball Surface-Defect
      Inspection.
AB  - Steel ball surface-defect inspection was performed by using a new saddle-type
      eddy current sensor (SECS), which included a saddle coil and a signal
      conditioning circuit. The saddle coil was directly wound on the steel ball's
      outer bracket in a semi-circumferential direction. Driven by a friction wheel,
      the test steel ball rotated in a one-dimensional direction, such that the steel
      ball surface was fully scanned by the SECS. There were two purposes for using the
      SECS in the steel ball inspection system: one was to reduce the complexity of the
      unfolding wheel of the surface deployment mechanism, and the other was to reduce
      the difficulty of sensor processing and installation. Experiments were carried
      out on bearing steel balls in diameter of 8 mm with three types of representative
      and typical defects by using the SECS, and the results showed that the inspection
      system can detect surface defects as small as 0.05 mm in width and 0.1 mm in
      depth with high-repetition detection accuracy, and the detection efficiency of 5
      pcs/s, which meet the requirement for inspecting ISO grade 10 bearing steel
      balls. The feasibility of detecting steel ball surface defects by SECS was
      verified.

PMID- 29206155
TI  - Structurally Oriented Nano-Sheets in Co Thin Films: Changing Their Anisotropic
      Physical Properties by Thermally-Induced Relaxation.
AB  - We show how nanocrystalline Co films formed by separated oblique nano-sheets
      display anisotropy in their resistivity, magnetization process, surface nano
      morphology and optical transmission. After performing a heat treatment at 270 
      degrees C, these anisotropies decrease. This loss has been monitored measuring
      the resistivity as a function of temperature. The resistivity measured parallel
      to the direction of the nano-sheets has been constant up to 270  degrees C, but
      it decreases when measured perpendicular to the nano-sheets. This suggests the
      existence of a structural relaxation, which produces the change of the Co nano
      sheets during annealing. The changes in the nano-morphology and the local
      chemical composition of the films at the nanoscale after heating above 270 
      degrees C have been analysed by scanning transmission electron microscopy (STEM).
      Thus, an approach and coalescence of the nano-sheets have been directly
      visualized. The spectrum of activation energies of this structural relaxation has
      indicated that the coalescence of the nano-sheets has taken place between 1.2 and
      1.7 eV. In addition, an increase in the size of the nano-crystals has occurred in
      the samples annealed at 400  degrees C. This study may be relevant for the
      application in devices working, for example, in the GHz range and to achieve the
      retention of the anisotropy of these films at higher temperatures.

PMID- 29206156
TI  - Identification, In Vitro Testing and Molecular Docking Studies of Microginins'
      Mechanism of Angiotensin-Converting Enzyme Inhibition.
AB  - Cyanobacteria are able to produce a wide range of secondary metabolites,
      including toxins and protease inhibitors, with diverse biological activities.
      Microginins are small linear peptides biosynthesized by cyanobacteria species
      that act against proteases. The aim of this study was to isolate and identify
      microginins produced by the LTPNA08 strain of Microcystis aeruginosa, as well as
      to verify their potential to inhibit angiotensin-converting enzyme (ACE; EC.
      3.4.15.1) using in vitro and in silico methods. The fractionation of
      cyanobacterial extracts was performed by liquid chromatography and the presence
      of microginins was monitored by both LC-MS and an ACE inhibition assay. Enzyme
      inhibition was assayed by ACE with hippuryl-histidyl-leucine as the substrate;
      monitoring of hippuric acid was performed by HPLC-DAD. Isolated microginins were
      confirmed by mass spectrometry and were used to carry out the enzymatic assay.
      Molecular docking was used to evaluate microginin 770 (MG 770) and captopril
      (positive control), in order to predict similar binding interactions and
      determine the inhibitory action of ACE. The enzyme assay confirmed that MG 770
      can efficiently inhibit ACE, with an IC50 equivalent to other microginins. MG 770
      presented with comparable interactions with ACE, having features in common with
      commercial inhibitors such as captopril and enalaprilate, which are frequently
      used in the treatment of hypertension in humans.

PMID- 29206157
TI  - Effect of Graphene Oxide (GO) on the Morphology and Microstructure of Cement
      Hydration Products.
AB  - In this study, the effects of graphene oxide (GO) on the microstructure of cement
      mortars were studied using scanning electron microscopy (SEM), thermogravimetric
      (TG), and X-ray diffraction (XRD) techniques. Cement mortar samples with
      different proportions of GO (0.02, 0.04, 0.06, and 0.08 wt % based on the weight
      of cement) were prepared. The test results showed that GO affected the
      crystallization of cement hydration products, C-S-H (calcium silicate hydrate is
      the main hydrate product) and CH (calcium hydroxide). The morphology of hydration
      products changed with the increase of GO content. Furthermore, the results of XRD
      analyses showed that the diffraction peak intensity and the crystal grain size of
      CH (001), (100), (101), and (102) for GO samples increased considerably compared
      with the control sample. Based on the results, it can be understood that GO can
      modify the crystal surface of CH, leading to the formation of larger crystals.

PMID- 29206159
TI  - Energy Management in Smart Cities Based on Internet of Things: Peak Demand
      Reduction and Energy Savings.
AB  - Around the globe, innovation with integrating information and communication
      technologies (ICT) with physical infrastructure is a top priority for governments
      in pursuing smart, green living to improve energy efficiency, protect the
      environment, improve the quality of life, and bolster economy competitiveness.
      Cities today faces multifarious challenges, among which energy efficiency of
      homes and residential dwellings is a key requirement. Achieving it successfully
      with the help of intelligent sensors and contextual systems would help build
      smart cities of the future. In a Smart home environment Home Energy Management
      plays a critical role in finding a suitable and reliable solution to curtail the
      peak demand and achieve energy conservation. In this paper, a new method named as
      Home Energy Management as a Service (HEMaaS) is proposed which is based on neural
      network based Q-learning algorithm. Although several attempts have been made in
      the past to address similar problems, the models developed do not cater to
      maximize the user convenience and robustness of the system. In this paper,
      authors have proposed an advanced Neural Fitted Q-learning method which is self
      learning and adaptive. The proposed method provides an agile, flexible and energy
      efficient decision making system for home energy management. A typical Canadian
      residential dwelling model has been used in this paper to test the proposed
      method. Based on analysis, it was found that the proposed method offers a fast
      and viable solution to reduce the demand and conserve energy during peak period.
      It also helps reducing the carbon footprint of residential dwellings. Once
      adopted, city blocks with significant residential dwellings can significantly
      reduce the total energy consumption by reducing or shifting their energy demand
      during peak period. This would definitely help local power distribution companies
      to optimize their resources and keep the tariff low due to curtailment of peak
      demand.

PMID- 29206158
TI  - Anti-Candida Activity of Bursera morelensis Ramirez Essential Oil and Two
      Compounds, alpha-Pinene and gamma-Terpinene-An In Vitro Study.
AB  - The candidiasis caused by C. albicans is a public health problem. The abuse of
      antifungals has contributed to the development of resistance. B. morelensis has
      demonstrated antibacterial and antifungal activities. In this work the activity
      of the essential oil of B. morelensis was evaluated and for its two pure
      compounds with analysis of the different mechanisms of pathogenesis important for
      C. albicans. The essential oil was obtained by the hydro-distillation method and
      analyzed using GC-MS. The anti-Candida activity was compared between to essential
      oil, alpha-Pinene and gamma-Terpinene. GC-MS of the essential oil demonstrated
      the presence of 13 compounds. The essential oil showed antifungal activity
      against four C. albicans strains. The most sensitive strain was C. albicans 14065
      (MFC 2.0 mg/mL and MIC50 0.125 mg/mL) with alpha-Pinene and gamma-Terpinene
      having MFCs of 4.0 and 16.0 mg/mL respectively. The essential oil inhibited the
      growth of the germ tube in 87.94% (8.0 mg/mL). Furthermore, it was observed that
      the essential oil diminishes the transcription of the gene INT1. This work
      provides evidence that confirms the anti-Candida activity of the B. morelensis
      essential oil and its effect on the growth of the germ tube and transcription of
      the gene INT1.

PMID- 29206160
TI  - Comparative Analysis of Cotton Small RNAs and Their Target Genes in Response to
      Salt Stress.
AB  - Small RNAs play an important role in regulating plant responses to abiotic
      stress. Depending on the method of salt application, whether sudden or gradual,
      plants may experience either salt shock or salt stress, respectively. In this
      study, small RNA expression in response to salt shock and long-term salt stress
      in parallel experiments was described. Cotton small RNA libraries were
      constructed and sequenced under normal conditions, as well as sudden and gradual
      salt application. A total of 225 cotton microRNAs (miRNAs) were identified and of
      these 24 were novel miRNAs. There were 88 and 75 miRNAs with differential
      expression under the salt shock and long-term salt stress, respectively. Thirty
      one transcripts were found to be targets of 20 miRNA families. Eight targets
      showed a negative correlation in expression with their corresponding miRNAs. We
      also identified two TAS3s with two near-identical 21-nt trans-acting small
      interfering RNA (tasiRNA)-Auxin Response Factors (ARFs) that coaligned with the
      phases D7(+) and D8(+) in three Gossypium species. The miR390/tasiRNA-ARFs/ARF4
      pathway was identified and showed altered expression under salt stress. The
      identification of these small RNAs as well as elucidating their functional
      significance broadens our understanding of post-transcriptional gene regulation
      in response to salt stress.

PMID- 29206161
TI  - Ethnobotanical Survey, Preliminary Physico-Chemical and Phytochemical Screening
      of Salvia argentea (L.) Used by Herbalists of the Saida Province in Algeria.
AB  - An ethnobotanical study was carried out in the Saida region among herbalists to
      evaluate the use of Salvia argentea (L.), a plant species native from North
      Africa belonging to the Lamiaceae family. Forty-two herbalists were interviewed
      individually, aged between 30 and 70 years, all males, 52.38% of them having
      received a secondary education level and having performing their duties for more
      than a decade. This study showed that Salvia argentea is used specifically in the
      treatment of diseases of the respiratory system. The leaves are the most commonly
      used part, usually in the form of powder and exclusively administered orally. The
      preliminary results of the physicochemical characterization and the phytochemical
      screening of the powdered leaves of Salvia argentea attest to their safety and
      confer them a guarantee of phytotherapeutic quality.

PMID- 29206162
TI  - A 45 nm Stacked CMOS Image Sensor Process Technology for Submicron Pixel.
AB  - A submicron pixel's light and dark performance were studied by experiment and
      simulation. An advanced node technology incorporated with a stacked CMOS image
      sensor (CIS) is promising in that it may enhance performance. In this work, we
      demonstrated a low dark current of 3.2 e-/s at 60  degrees C, an ultra-low read
      noise of 0.90 e-.rms, a high full well capacity (FWC) of 4100 e-, and blooming of
      0.5% in 0.9 MUm pixels with a pixel supply voltage of 2.8 V. In addition, the
      simulation study result of 0.8 MUm pixels is discussed.

PMID- 29206163
TI  - Frozen Microemulsions for MAPLE Immobilization of Lipase.
AB  - Candida rugosa lipase (CRL) was deposited by matrix assisted pulsed laser
      evaporation (MAPLE) in order to immobilize the enzyme with a preserved native
      conformation, which ensures its catalytic functionality. For this purpose, the
      composition of the MAPLE target was optimized by adding the oil phase pentane to
      a water solution of the amino acid 3-(3,4-dihydroxyphenyl)-2-methyl-l-alanine (m
      DOPA), giving a target formed by a frozen water-lipase-pentane microemulsion.
      Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM)
      were used to investigate the structure of MAPLE deposited lipase films. FTIR
      deconvolution of amide I band indicated a reduction of unfolding and aggregation,
      i.e., a better preserved lipase secondary structure in the sample deposited from
      the frozen microemulsion target. AFM images highlighted the absence of big
      aggregates on the surface of the sample. The functionality of the immobilized
      enzyme to promote transesterification was determined by thin layer
      chromatography, resulting in a modified specificity.

PMID- 29206164
TI  - Dietary Consumption of Phenolic Acids and Prostate Cancer: A Case-Control Study
      in Sicily, Southern Italy.
AB  - Dietary polyphenols gained the interest of the scientific community due to their
      wide content in a variety of plant-derived foods and beverages commonly consumed,
      such as fruits, vegetables, coffee, tea, and cocoa. We aimed to investigate
      whether there was an association between dietary phenolic acid consumption and
      prostate cancer (PCa) in South Italy. We conducted a population-based case
      control study from January 2015 to December 2016 in a single institution of the
      municipality of Catania, southern Italy (Registration number: 41/2015). Patients
      with elevated PSA and/or suspicious PCa underwent transperineal prostate biopsy.
      A total of 118 histopathological-verified PCa cases were collected and a total of
      222 controls were selected from a sample of 2044 individuals. Dietary data were
      collected by using two food frequency questionnaires and data on the phenolic
      acids content in foods was obtained from the Phenol-Explorer database (www.phenol
      explorer.eu). Association between dietary intake of phenolic acids and PCa was
      calculated through logistic regression analysis. We found lower levels of caffeic
      acid (2.28 mg/day vs. 2.76 mg/day; p < 0.05) and ferulic acid (2.80 mg/day vs.
      4.04 mg/day; p < 0.01) in PCa when compared to controls. The multivariate
      logistic regression showed that both caffeic acid (OR = 0.32; p < 0.05) and
      ferulic acid (OR = 0.30; p < 0.05) were associated with reduced risk of PCa.
      Higher intake of hydroxybenzoic acids and caffeic acids were associated with
      lower risk of advanced PCa. High intake of caffeic acid and ferulic acid may be
      associated with reduced risk of PCa.

PMID- 29206166
TI  - The Impact of Hemodialysis on Spatio-Temporal Characteristics of Gait and Role of
      Exercise: A Systematic Review.
AB  - Background: People with end-stage kidney disease (ESKD) on hemodialysis (HD)
      commonly have functional impairments. The purpose of this systematic review was
      to evaluate the effect of HD on spatio-temporal characteristics of gait, and
      effect of exercise on these parameters. Methods: Electronic databases were
      searched to identify relevant citations. Extracted data was computed using a
      random effects model for means (Hedges' and 95% confidence interval (CI).
      Results: 27 studies met inclusion criteria. Mean values: gait speed (GS)-1.0 m/s
      (CI: 0.9-1.1 m/s; 16 studies), fast walking speed (FWS)-1.5 m/s (CI: 1.3-1.6 m/s;
      7 studies), timed get-up & go test (TUG) -6.8 s (CI: 6.1-7.5 s; 2 studies), walk
      tests (WT) 193.0 s (CI: 116.0-270.0; 5 studies), 6 min-walk-test (6MWT)-386.6 m
      (CI: 243.2-530.0 m; 11 studies). 4 studies compared participants on HD with
      normal controls and 10 studies evaluated the effect of nutrition/exercise.
      Conclusions: Compared to age-matched populations, people with ESKD/HD had
      significantly slower GS and reduced walk distances; with intervention, the change
      in the distance walked was significant. Further research is required to evaluate
      the effect of HD on gait parameters, and the type of exercise/nutrition that will
      lead to meaningful changes.

PMID- 29206167
TI  - scRNASeqDB: A Database for RNA-Seq Based Gene Expression Profiles in Human Single
      Cells.
AB  - Single-cell RNA sequencing (scRNA-Seq) is rapidly becoming a powerful tool for
      high-throughput transcriptomic analysis of cell states and dynamics at the single
      cell level. Both the number and quality of scRNA-Seq datasets have dramatically
      increased recently. A database that can comprehensively collect, curate, and
      compare expression features of scRNA-Seq data in humans has not yet been built.
      Here, we present scRNASeqDB, a database that includes almost all the currently
      available human single cell transcriptome datasets (n = 38) covering 200 human
      cell lines or cell types and 13,440 samples. Our online web interface allows
      users to rank the expression profiles of the genes of interest across different
      cell types. It also provides tools to query and visualize data, including Gene
      Ontology and pathway annotations for differentially expressed genes between cell
      types or groups. The scRNASeqDB is a useful resource for single cell
      transcriptional studies. This database is publicly available at
      bioinfo.uth.edu/scrnaseqdb/.

PMID- 29206165
TI  - Current Research on Non-Coding Ribonucleic Acid (RNA).
AB  - Non-coding ribonucleic acid (RNA) has without a doubt captured the interest of
      biomedical researchers. The ability to screen the entire human genome with high
      throughput sequencing technology has greatly enhanced the identification,
      annotation and prediction of the functionality of non-coding RNAs. In this
      review, we discuss the current landscape of non-coding RNA research and
      quantitative analysis. Non-coding RNA will be categorized into two major groups
      by size: long non-coding RNAs and small RNAs. In long non-coding RNA, we discuss
      regular long non-coding RNA, pseudogenes and circular RNA. In small RNA, we
      discuss miRNA, transfer RNA, piwi-interacting RNA, small nucleolar RNA, small
      nuclear RNA, Y RNA, single recognition particle RNA, and 7SK RNA. We elaborate on
      the origin, detection method, and potential association with disease, putative
      functional mechanisms, and public resources for these non-coding RNAs. We aim to
      provide readers with a complete overview of non-coding RNAs and incite additional
      interest in non-coding RNA research.

PMID- 29206169
TI  - Monitoring Traffic Information with a Developed Acceleration Sensing Node.
AB  - In this paper, an acceleration sensing node for pavement vibration was developed
      to monitor traffic information, including vehicle speed, vehicle types, and
      traffic flow, where a hardware design with low energy consumption and node
      encapsulation could be accomplished. The service performance of the sensing node
      was evaluated, by methods including waterproof test, compression test, sensing
      performance analysis, and comparison test. The results demonstrate that the
      sensing node is low in energy consumption, high in strength, IPX8 waterproof, and
      high in sensitivity and resolution. These characteristics can be applied to
      practical road environments. Two sensing nodes were spaced apart in the direction
      of travelling. In the experiment, three types of vehicles passed by the
      monitoring points at several different speeds and values of d (the distance
      between the sensor and the nearest tire center line). Based on cross-correlation
      with kernel pre-smoothing, a calculation method was applied to process the raw
      data. New algorithms for traffic flow, speed, and axle length were proposed.
      Finally, the effects of vehicle speed, vehicle weight, and d value on
      acceleration amplitude were statistically evaluated. It was found that the
      acceleration sensing node can be used for traffic flow, vehicle speed, and other
      types of monitoring.

PMID- 29206168
TI  - Significance and Diagnostic Role of Antimicrobial Cathelicidins (LL-37) Peptides
      in Oral Health.
AB  - Cathelicidins are a group of oral antimicrobial peptides that play multiple vital
      roles in the human body, such as their antimicrobial (broad spectrum) role
      against oral microbes, wound healing, and angiogenesis, with recent evidences
      about their role in cancer regulation. Cathelicidins are present in humans and
      other mammals as well. By complex interactions with the microenvironment, it
      results in pro-inflammatory effects. Many in vitro and in vivo experiments have
      been conducted to ultimately conclude that these unique peptides play an
      essential role in innate immunity. Peptides are released in the precursor form
      (defensins), which after cleavage results in cathelicidins formation. Living in
      the era where the major focus is on non-invasive and nanotechnology, this
      ultimately leads to further advancements in the field of salivaomics. Based on
      current spotlight innovations, we have highlighted the biochemistry, mode of
      action, and the importance of cathelicidins in the oral cavity.

PMID- 29206170
TI  - Pollution Emissions, Environmental Policy, and Marginal Abatement Costs.
AB  - Pollution emissions impose serious social negative externalities, especially in
      terms of public health. To reduce pollution emissions cost-effectively, the
      marginal abatement costs (MACs) of pollution emissions must be determined. Since
      the industrial sectors are the essential pillars of China's economic growth, as
      well as leading energy consumers and sulfur dioxide (SO2) emitters, estimating
      MACs of SO2 emissions at the industrial level can provide valuable information
      for all abatement efforts. This paper tries to address the critical and essential
      issue in pollution abatement: How do we determine the MACs of pollution emissions
      in China? This paper first quantifies the SO2 emission contribution of different
      industrial sectors in the Chinese economy by an Input-Output method and then
      estimates MACs of SO2 for industrial sectors at the national level, provincial
      level, and sectoral level by the shadow price theory. Our results show that six
      sectors (e.g., the Mining and Washing of Coal sector) should be covered in the
      Chinese pollution emission trading system. We have also found that the lowest SO2
      shadow price is 2000 Yuan/ton at the national level, and that shadow prices
      should be set differently at the provincial level. Our empirical study has
      several important policy implications, e.g., the estimated MACs may be used as a
      pricing benchmark through emission allowance allocation. In this paper, the MACs
      of industrial sectors are calculated from the national, provincial and sectoral
      levels; therefore, we provide an efficient framework to track the complex
      relationship between sectors and provinces.

PMID- 29206171
TI  - Kin Selection in the RNA World.
AB  - Various steps in the RNA world required cooperation. Why did life's first
      inhabitants, from polymerases to synthetases, cooperate? We develop kin selection
      models of the RNA world to answer these questions. We develop a very simple model
      of RNA cooperation and then elaborate it to model three relevant issues in RNA
      biology: (1) whether cooperative RNAs receive the benefits of cooperation; (2)
      the scale of competition in RNA populations; and (3) explicit replicator
      diffusion and survival. We show: (1) that RNAs are likely to express partial
      cooperation; (2) that RNAs will need mechanisms for overcoming local competition;
      and (3) in a specific example of RNA cooperation, persistence after replication
      and offspring diffusion allow for cooperation to overcome competition. More
      generally, we show how kin selection can unify previously disparate answers to
      the question of RNA world cooperation.

PMID- 29206172
TI  - Melatonin Efficacy in Obese Leptin-Deficient Mice Heart.
AB  - Cardiomyocytes are particularly sensitive to oxidative damage due to the link
      between mitochondria and sarcoplasmic reticulum necessary for calcium flux and
      contraction. Melatonin, important indoleamine secreted by the pineal gland during
      darkness, also has important cardioprotective properties. We designed the present
      study to define morphological and ultrastructural changes in cardiomyocytes and
      mainly in mitochondria of an animal model of obesity (ob/ob mice), when treated
      orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week
      of life). We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter
      myofibrillar compartments are often devoid of cristae with an abnormally large
      size, which are called mega-mitochondria. Moreover, in ob/ob mice the
      hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE), a
      marker of lipid peroxidation but scarce degree of mitofusin2, indicative of
      mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores
      mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and
      p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level,
      adipose tissue depot strictly associated with myocardium infarction, melatonin
      reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin
      expressions. In summary, melatonin might represent a safe dietary adjuvant to
      hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre
      diabetic obese mice at 13 weeks of life.

PMID- 29206173
TI  - Histone MacroH2A1: A Chromatin Point of Intersection between Fasting, Senescence
      and Cellular Regeneration.
AB  - Histone variants confer chromatin unique properties. They have specific genomic
      distribution, regulated by specific deposition and removal machineries. Histone
      variants, mostly of canonical histones H2A, H2B and H3, have important roles in
      early embryonic development, in lineage commitment of stem cells, in the converse
      process of somatic cell reprogramming to pluripotency and, in some cases, in the
      modulation of animal aging and life span. MacroH2A1 is a variant of histone H2A,
      present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2,
      regulating cell plasticity and proliferation, during pluripotency and
      tumorigenesis. Furthermore, macroH2A1 participates in the formation of senescence
      associated heterochromatic foci (SAHF) in senescent cells, and multiple lines of
      evidence in genetically modified mice suggest that macroH2A1 integrates
      nutritional cues from the extracellular environment to transcriptional programs.
      Here, we review current molecular evidence based on next generation sequencing
      data, cell assays and in vivo models supporting different mechanisms that could
      mediate the function of macroH2A1 in health span and life span. We will further
      discuss context-dependent and isoform-specific functions. The aim of this review
      is to provide guidance to assess histone variant macroH2A1 potential as a
      therapeutic intervention point.

PMID- 29206175
TI  - LiDAR-IMU Time Delay Calibration Based on Iterative Closest Point and Iterated
      Sigma Point Kalman Filter. Sensors 2017, 17, 539.
AB  - The IMU consists of three gyros and three accelerometers [...].

PMID- 29206174
TI  - A Looking-Glass of Non-coding RNAs in oral cancer.
AB  - Oral cancer is a multifactorial pathology and is characterized by the lack of
      efficient treatment and accurate diagnostic tools. This is mainly due the late
      diagnosis; therefore, reliable biomarkers for the timely detection of the disease
      and patient stratification are required. Non-coding RNAs (ncRNAs) are key
      elements in the physiological and pathological processes of various cancers,
      which is also reflected in oral cancer development and progression. A better
      understanding of their role could give a more thorough perspective on the future
      treatment options for this cancer type. This review offers a glimpse into the
      ncRNA involvement in oral cancer, which can help the medical community tap into
      the world of ncRNAs and lay the ground for more powerful diagnostic, prognostic
      and treatment tools for oral cancer that will ultimately help build a brighter
      future for these patients.

PMID- 29206176
TI  - Kisspeptin-10 Induces beta-Casein Synthesis via GPR54 and Its Downstream
      Signaling Pathways in Bovine Mammary Epithelial Cells.
AB  - Kisspeptins (Kps) play a key role in the regulation of GnRH axis and as an anti
      metastasis agent by binding with GPR54. Recently, we observed that the expression
      of GPR54 was higher in the lactating mammary tissues of dairy cows with high
      quality milk (0.81 +/- 0.13 kg/day of milk protein yield; 1.07 +/- 0.18 kg/day of
      milk fat yield) than in those with low-quality milk (0.51 +/- 0.14 kg/day of milk
      protein yield; 0.67 +/- 0.22 kg/day of milk fat yield). We hypothesized that Kp
      10 might regulate the milk protein, beta-casein (CSN2) synthesis via GPR54 and
      its downstream signaling. First, we isolated the bovine mammary epithelial cells
      (bMECs) from lactating Holstein dairy cows, and treated them with different
      concentrations of Kp-10. Compared with the control cells, the synthesis of CSN2
      is significantly increased at a concentration of 100 nM of Kp-10. In addition,
      the increased effect of CSN2 synthesis was blocked when the cells were pre
      treated with the selective inhibitor of GPR54 Peptide-234 (P-234). Mechanistic
      study revealed that Kp-10 activated ERK1/2, AKT, mTOR and STAT5 in bMECs.
      Moreover, inhibiting ERK1/2, AKT, mTOR and STAT5 with U0126, MK2206, Rapamycin
      and AG490 could block the effects of Kp-10. Together, these results demonstrate
      that Kp-10 facilitates the synthesis of CSN2 via GPR54 and its downstream
      signaling pathways mTOR, ERK1/2, STAT5 and AKT.

PMID- 29206177
TI  - New Therapeutic Agent against Arterial Thrombosis: An Iridium(III)-Derived
      Organometallic Compound.
AB  - Platelet activation plays a major role in cardio and cerebrovascular diseases,
      and cancer progression. Disruption of platelet activation represents an
      attractive therapeutic target for reducing the bidirectional cross talk between
      platelets and tumor cells. Platinum (Pt) compounds have been used for treating
      cancer. Hence, replacing Pt with iridium (Ir) is considered a potential
      alternative. We recently developed an Ir(III)-derived complex, [Ir(Cp*)1-(2
      pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine Cl]BF4 (Ir-11), which
      exhibited strong antiplatelet activity; hence, we assessed the therapeutic
      potential of Ir-11 against arterial thrombosis. In collagen-activated platelets,
      Ir-11 inhibited platelet aggregation, adenosine triphosphate (ATP) release,
      intracellular Ca2+ mobilization, P-selectin expression, and OH. formation, as
      well as the phosphorylation of phospholipase Cgamma2 (PLCgamma2), protein kinase
      C (PKC), mitogen-activated protein kinases (MAPKs), and Akt. Neither the
      adenylate cyclase inhibitor nor the guanylate cyclase inhibitor reversed the Ir
      11-mediated antiplatelet effects. In experimental mice, Ir-11 prolonged the
      bleeding time and reduced mortality associated with acute pulmonary
      thromboembolism. Ir-11 plays a crucial role by inhibiting platelet activation
      through the inhibition of the PLCgamma2-PKC cascade, and the subsequent
      suppression of Akt and MAPK activation, ultimately inhibiting platelet
      aggregation. Therefore, Ir-11 can be considered a new therapeutic agent against
      either arterial thrombosis or the bidirectional cross talk between platelets and
      tumor cells.

PMID- 29206179
TI  - Antioxidant Potential of Fruit Juice with Added Chokeberry Powder (Aronia
      melanocarpa).
AB  - The purpose of this study was to determine the possibility of using chokeberry
      powder as a supplement in apple juice to increase the nutritional value of the
      final product with the aim of developing a new functional food product. Also, to
      determine the influence of ultrasound assisted extraction on the bioactive
      compounds content, nutritional composition and antioxidant potential of apple
      juice with added chokeberry powder. The juice samples with added chokeberry
      powder had higher antioxidant capacity, irrespective of the extraction technique
      used. Apple juice samples with added chokeberry powder treated with high
      intensity ultrasound had significantly higher content of all analyzed bioactive
      compounds. The application of high intensity ultrasound significantly reduced the
      extraction time of the plant material. A positive correlation between vitamin C
      content, total phenols, flavonoids and anthocyanins content and antioxidant
      capacity was determined in juice samples with added chokeberry powder treated
      with high intensity ultrasound.

PMID- 29206178
TI  - Around and beyond 53BP1 Nuclear Bodies.
AB  - Within the nucleus, sub-nuclear domains define territories where specific
      functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate
      nuclear factors and that can be observed microscopically. Recently, NBs
      containing the p53 binding protein 1 (53BP1), a key component of the DNA damage
      response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase,
      in daughter cells, while DNA damage was generated in mother cells and not
      properly processed. Unlike most NBs involved in transcriptional processes,
      replication has proven to be key for 53BP1 NBs, with replication stress leading
      to the formation of these large chromatin domains in daughter cells. In this
      review, we expose the composition and organization of 53BP1 NBs and focus on
      recent findings regarding their regulation and dynamics. We then concentrate on
      the importance of the replication stress, examine the relation of 53BP1 NBs with
      DNA damage and discuss their dysfunction.

PMID- 29206181
TI  - The Relationships between PM2.5 and Meteorological Factors in China: Seasonal and
      Regional Variations.
AB  - The interactions between PM2.5 and meteorological factors play a crucial role in
      air pollution analysis. However, previous studies that have researched the
      relationships between PM2.5 concentration and meteorological conditions have been
      mainly confined to a certain city or district, and the correlation over the whole
      of China remains unclear. Whether spatial and seasonal variations exist deserves
      further research. In this study, the relationships between PM2.5 concentration
      and meteorological factors were investigated in 68 major cities in China for a
      continuous period of 22 months from February 2013 to November 2014, at season,
      year, city, and regional scales, and the spatial and seasonal variations were
      analyzed. The meteorological factors were relative humidity (RH), temperature
      (TEM), wind speed (WS), and surface pressure (PS). We found that spatial and
      seasonal variations of their relationships with PM2.5 exist. Spatially, RH is
      positively correlated with PM2.5 concentration in north China and Urumqi, but the
      relationship turns to negative in other areas of China. WS is negatively
      correlated with PM2.5 everywhere except for Hainan Island. PS has a strong
      positive relationship with PM2.5 concentration in northeast China and mid-south
      China, and in other areas the correlation is weak. Seasonally, the positive
      correlation between PM2.5 concentration and RH is stronger in winter and spring.
      TEM has a negative relationship with PM2.5 in autumn and the opposite in winter.
      PS is more positively correlated with PM2.5 in autumn than in other seasons. Our
      study investigated the relationships between PM2.5 and meteorological factors in
      terms of spatial and seasonal variations, and the conclusions about the
      relationships between PM2.5 and meteorological factors are more comprehensive and
      precise than before. We suggest that the variations could be considered in PM2.5
      concentration prediction and haze control to improve the prediction accuracy and
      policy efficiency.

PMID- 29206180
TI  - Composition and Bioactivity of Essential Oil from Citrus grandis (L.) Osbeck
      'Mato Peiyu' Leaf.
AB  - 'Mato Peiyu' pomelo (Citrus grandis (L.) Osbeck 'Mato Peiyu') leaves from pruning
      are currently an agricultural waste. The aim of this study was to isolate
      essential oils from these leaves through steam distillation (SD) and solvent-free
      microwave extraction (SFME) and to evaluate their applicability to skin care by
      analyzing their antimicrobial, antioxidant (diphenyl-1-picrylhydrazyl scavenging
      assay, beta-carotene/linoleic acid assay, and nitric oxide scavenging assay),
      anti-inflammatory (5-lipoxygenase inhibition assay), and antityrosinase
      activities. The gas chromatography-mass spectrometry results indicated that the
      main components of 'Mato Peiyu' leaf essential oils were citronellal and
      citronellol, with a total percentage of 50.71% and 59.82% for SD and SFME,
      respectively. The highest bioactivity among all assays was obtained for 5
      lipoxygenase inhibition, with an IC50 value of 0.034% (v/v). The MIC90 of the
      antimicrobial activity of essential oils against Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus, and Candida albicans ranged from 0.086% to
      0.121% (v/v). Citronellal and citronellol were the main contributors, accounting
      for at least 54.58% of the essential oil's bioactivity. This paper is the first
      to report the compositions and bioactivities of 'Mato Peiyu' leaf essential oil,
      and the results imply that the pomelo leaf essential oil may be applied in skin
      care.

PMID- 29206182
TI  - Phase-Sensitive Surface Plasmon Resonance Sensors: Recent Progress and Future
      Prospects.
AB  - Surface plasmon resonance (SPR) is an optical sensing technique that is capable
      of performing real-time, label-free and high-sensitivity monitoring of molecular
      interactions. SPR biosensors can be divided according to their operating
      principles into angle-, wavelength-, intensity- and phase-interrogated devices.
      With their complex optical configurations, phase-interrogated SPR sensors
      generally provide higher sensitivity and throughput, and have thus recently
      emerged as prominent biosensing devices. To date, several methods have been
      developed for SPR phase interrogation, including heterodyne detection,
      polarimetry, shear interferometry, spatial phase modulation interferometry and
      temporal phase modulation interferometry. This paper summarizes the fundamentals
      of phase-sensitive SPR sensing, reviews the available methods for phase
      interrogation of these sensors, and discusses the future prospects for and trends
      in the development of this technology.

PMID- 29206183
TI  - Gaming Device Usage Patterns Predict Internet Gaming Disorder: Comparison across
      Different Gaming Device Usage Patterns.
AB  - Gaming behaviors have been significantly influenced by smartphones. This study
      was designed to explore gaming behaviors and clinical characteristics across
      different gaming device usage patterns and the role of the patterns on Internet
      gaming disorder (IGD). Responders of an online survey regarding smartphone and
      online game usage were classified by different gaming device usage patterns: (1)
      individuals who played only computer games; (2) individuals who played computer
      games more than smartphone games; (3) individuals who played computer and
      smartphone games evenly; (4) individuals who played smartphone games more than
      computer games; (5) individuals who played only smartphone games. Data on
      demographics, gaming-related behaviors, and scales for Internet and smartphone
      addiction, depression, anxiety disorder, and substance use were collected.
      Combined users, especially those who played computer and smartphone games evenly,
      had higher prevalence of IGD, depression, anxiety disorder, and substance use
      disorder. These subjects were more prone to develop IGD than reference group
      (computer only gamers) (B = 0.457, odds ratio = 1.579). Smartphone only gamers
      had the lowest prevalence of IGD, spent the least time and money on gaming, and
      showed lowest scores of Internet and smartphone addiction. Our findings suggest
      that gaming device usage patterns may be associated with the occurrence, course,
      and prognosis of IGD.

PMID- 29206184
TI  - High-Density Linkage Map Construction and Mapping of Salt-Tolerant QTLs at
      Seedling Stage in Upland Cotton Using Genotyping by Sequencing (GBS).
AB  - Over 6% of agricultural land is affected by salinity. It is becoming obligatory
      to use saline soils, so growing salt-tolerant plants is a priority. To gain an
      understanding of the genetic basis of upland cotton tolerance to salinity at
      seedling stage, an intra-specific cross was developed from CCRI35, tolerant to
      salinity, as female with Nan Dan (NH), sensitive to salinity, as the male. A
      genetic map of 5178 SNP markers was developed from 277 F2:3 populations. The map
      spanned 4768.098 cM, with an average distance of 0.92 cM. A total of 66 QTLs for
      10 traits related to salinity were detected in three environments (0, 110, and
      150 mM salt treatment). Only 14 QTLs were consistent, accounting for 2.72% to
      9.87% of phenotypic variation. Parental contributions were found to be in the
      ratio of 3:1, 10 QTLs from the sensitive and four QTLs from the resistant parent.
      Five QTLs were located in At and nine QTLs in the Dt sub-genome. Moreover, eight
      clusters were identified, in which 12 putative key genes were found to be related
      to salinity. The GBS-SNPs-based genetic map developed is the first high-density
      genetic map that has the potential to provide deeper insights into upland cotton
      salinity tolerance. The 12 key genes found in this study could be used for QTL
      fine mapping and cloning for further studies.

PMID- 29206187
TI  - A Study about Kalman Filters Applied to Embedded Sensors.
AB  - Over the last decade, smart sensors have grown in complexity and can now handle
      multiple measurement sources. This work establishes a methodology to achieve
      better estimates of physical values by processing raw measurements within a
      sensor using multi-physical models and Kalman filters for data fusion. A driving
      constraint being production cost and power consumption, this methodology focuses
      on algorithmic complexity while meeting real-time constraints and improving both
      precision and reliability despite low power processors limitations. Consequently,
      processing time available for other tasks is maximized. The known problem of
      estimating a 2D orientation using an inertial measurement unit with automatic
      gyroscope bias compensation will be used to illustrate the proposed methodology
      applied to a low power STM32L053 microcontroller. This application shows
      promising results with a processing time of 1.18 ms at 32 MHz with a 3.8% CPU
      usage due to the computation at a 26 Hz measurement and estimation rate.

PMID- 29206185
TI  - Predictive and Experimental Approaches for Elucidating Protein-Protein
      Interactions and Quaternary Structures.
AB  - The elucidation of protein-protein interactions is vital for determining the
      function and action of quaternary protein structures. Here, we discuss the
      difficulty and importance of establishing protein quaternary structure and review
      in vitro and in silico methods for doing so. Determining the interacting partner
      proteins of predicted protein structures is very time-consuming when using in
      vitro methods, this can be somewhat alleviated by use of predictive methods.
      However, developing reliably accurate predictive tools has proved to be
      difficult. We review the current state of the art in predictive protein
      interaction software and discuss the problem of scoring and therefore ranking
      predictions. Current community-based predictive exercises are discussed in
      relation to the growth of protein interaction prediction as an area within these
      exercises. We suggest a fusion of experimental and predictive methods that make
      use of sparse experimental data to determine higher resolution predicted protein
      interactions as being necessary to drive forward development.

PMID- 29206186
TI  - Genomic Characterisation of Vinegar Hill Virus, An Australian Nairovirus Isolated
      in 1983 from Argas Robertsi Ticks Collected from Cattle Egrets.
AB  - This report describes the near complete genomic sequence and subsequent analysis
      of Vinegar Hill virus (VINHV; tentative member of the genus Orthonairovirus,
      family Nairoviridae, order Bunyavirales). VINHV is the second nairovirus reported
      to be isolated on mainland Australia and the first to be sequenced and analysed.
      Our genetic analysis shows that VINHV belongs to the Dera Ghazi Khan genogroup, a
      group of viruses previously isolated in other parts of the world including Asia,
      South Africa, and the USA. We discuss possible routes of entry for nairoviruses
      into Australia and the need to understand the virome of Australian ticks in the
      context of new and emerging disease.

PMID- 29206188
TI  - Lightweight Biometric Sensing for Walker Classification Using Narrowband RF
      Links.
AB  - This article proposes a lightweight biometric sensing system using ubiquitous
      narrowband radio frequency (RF) links for path-dependent walker classification.
      The fluctuated received signal strength (RSS) sequence generated by human motion
      is used for feature representation. To capture the most discriminative
      characteristics of individuals, a three-layer RF sensing network is organized for
      building multiple sampling links at the most common heights of upper limbs,
      thighs, and lower legs. The optimal parameters of sensing configuration, such as
      the height of link location and number of fused links, are investigated to
      improve sensory data distinctions among subjects, and the experimental results
      suggest that the synergistic sensing by using multiple links can contribute a
      better performance. This is the new consideration of using RF links in building a
      biometric sensing system. In addition, two types of classification methods
      involving vector quantization (VQ) and hidden Markov models (HMMs) are developed
      and compared for closed-set walker recognition and verification. Experimental
      studies in indoor line-of-sight (LOS) and non-line-of-sight (NLOS) scenarios are
      conducted to validate the proposed method.

PMID- 29206189
TI  - Vision System for Coarsely Estimating Motion Parameters for Unknown Fast Moving
      Objects in Space.
AB  - Motivated by biological interests in analyzing navigation behaviors of flying
      animals, we attempt to build a system measuring their motion states. To do this,
      in this paper, we build a vision system to detect unknown fast moving objects
      within a given space, calculating their motion parameters represented by
      positions and poses. We proposed a novel method to detect reliable interest
      points from images of moving objects, which can be hardly detected by general
      purpose interest point detectors. 3D points reconstructed using these interest
      points are then grouped and maintained for detected objects, according to a
      careful schedule, considering appearance and perspective changes. In the
      estimation step, a method is introduced to adapt the robust estimation procedure
      used for dense point set to the case for sparse set, reducing the potential risk
      of greatly biased estimation. Experiments are conducted against real scenes,
      showing the capability of the system of detecting multiple unknown moving objects
      and estimating their positions and poses.

PMID- 29206190
TI  - Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis:
      Structural, Biochemical Features and Therapeutic Potential.
AB  - Snake venom metalloproteinases (SVMPs) are predominant in viperid venoms, which
      provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes
      consist only of a single metalloproteinase domain. Despite sharing high sequence
      homology, only some of them induce hemorrhage. They have direct
      fibrin(ogen)olytic activity. Their main biological substrate is fibrin(ogen),
      whose Aalpha-chain is degraded rapidly and independently of activation of
      plasminogen. It is important to understand their biochemical and physiological
      mechanisms, as well as their applications, to study the etiology of some human
      diseases and to identify sites of potential intervention. As compared to all
      current antiplatelet therapies to treat cardiovascular events, the SVMPs have
      outstanding biochemical attributes: (a) they are insensitive to plasma serine
      proteinase inhibitors; (b) they have the potential to avoid bleeding risk; (c)
      mechanistically, they are inactivated/cleared by alpha2-macroglobulin that limits
      their range of action in circulation; and (d) few of them also impair platelet
      aggregation that represent an important target for therapeutic intervention. This
      review will briefly highlight the structure-function relationships of these few
      direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from
      Bothrops barnetti venom, that could be considered as potential agent to treat
      major thrombotic disorders. Some of their pharmacological advantages are compared
      with plasmin.

PMID- 29206191
TI  - The Metal Neurotoxins: An Important Role in Current Human Neural Epidemics?
AB  - Many published studies have illustrated that several of the present day
      neurological epidemics (autism, attention deficit disorder, Alzheimer's) cannot
      be correlated to any single neurotoxicant. However, the present scientific
      examination of the numerous global blood monitoring databases for adults that
      include the concentrations of the neurotoxic elements, aluminum (Al), arsenic
      (As), lead (Pb), manganese (Mn), mercury (Hg), and selenium (Se) clearly indicate
      that, when considered in combination, for some, the human body may become easily
      over-burdened. This can be explained by changes in modern lifestyles. Similar
      data, solely for pregnant women, have been examined confirming this. All these
      elements are seen to be present in the human body and at not insignificant
      magnitudes. Currently suggested minimum risk levels (MRL) for humans are
      discussed and listed together with averages of the reported distributions,
      together with their spread and maximum values. One observation is that many
      distributions for pregnant women are not too dissimilar from those of general
      populations. Women obviously have their individual baseline of neurotoxin values
      before pregnancy and any efforts to modify this to any significant degree is not
      yet clearly apparent. For any element, distribution shapes are reasonably similar
      showing broad distributions with extended tails with numerous outlier values.
      There are a certain fraction of people that lie well above the MRL values and may
      be at risk, especially if genetically susceptible. Additionally, synergistic
      effects between neurotoxins and with other trace metals are now also being
      reported. It appears prudent for women of child-bearing age to establish their
      baseline values well before pregnancy. Those at risk then can be better
      identified. Adequate instrumental testing now is commercially available for this.
      In addition, directives are necessary for vaccination programs to use only non
      neurotoxic adjuvants, especially for young children and all women of child
      bearing ages. Additionally, clearer directives concerning fish consumption must
      now be reappraised.

PMID- 29206192
TI  - Evaluation of Chronic Disease Prevention and Control Public Service Advertisement
      on the Awareness and Attitude Change among Urban Population in Chongqing, China:
      A Cross-Sectional Study.
AB  - The aim of this study is to evaluate the influence of public service advertising
      on the awareness and attitude of Chongqing urban citizens. The theme of the
      public service advertisement launched in Chongqing was chronic disease prevention
      and control. A self-designed questionnaire was used in an outdoor intercept
      survey to collect information about the perception of citizens toward the effect
      of the advertisement on awareness and attitude situation. Respondents had good
      knowledge of chronic disease (17.11 +/- 3.23, total score: 23), but only 58.4% of
      participants thought cancer is one type of chronic disease. The awareness of
      cancer as a chronic disease among the group who had seen this advertisement
      (63.6%) was higher than that of the group who had not seen the advertisement
      (56.5%) (p = 0.046). The attitude of respondents was good after watching the
      advertisement, approximately 77.4% of respondents attempted to remind their
      family and friends to prevent chronic diseases, roughly. 78.2% tried to persuade
      their family and friends to change their unhealthy lifestyle habits, and 84.7% of
      participants reported that the advertising increased the possibility of their own
      future lifestyle change. There was minimal change of awareness of the
      participants who saw the advertisement. This study did not show significant
      differences on chronic disease related knowledge between the participants who
      have seen the advertisement and who have not seen the advertisement. The public
      service advertisement may help participants improve the attitude of future
      behavior change. Further researches combining the sustained intervention and
      support through clinical and community health programs media campaigns are needed
      to support public health.

PMID- 29206194
TI  - Adipose Derived Stem Cells for Corneal Wound Healing after Laser Induced Corneal
      Lesions in Mice.
AB  - The aim of our study was to assess the clinical effectiveness of topical adipose
      derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by
      comparing epithelial repair, inflammation, and histological analysis between
      treatment arms. Corneal lesions were performed on both eyes of 40 mice by laser
      induced photorefractive keratectomy. All eyes were treated with topical
      azythromycin bid for three days. Mice were divided in three treatment groups (n =
      20), which included: control, stem cells and basic serum; which received topical
      treatment three times daily for five consecutive days. Biomicroscope assessments
      and digital imaging were performed by two masked graders at 30, 54, 78, 100, and
      172 h to analyze extent of fluorescein positive epithelial defect, corneal
      inflammation, etc. Immunohistochemical techniques were used in fixed eyes to
      assess corneal repair markers Ki67, alpha Smooth Muscle Actin (alpha-SMA) and E
      Cadherin. The fluorescein positive corneal lesion areas were significantly
      smaller in the stem cells group on days 1 (p < 0.05), 2 (p < 0.02) and 3. The
      stem cell treated group had slightly better and faster re-epithelization than the
      serum treated group in the initial phases. Comparative histological data showed
      signs of earlier and better corneal repair in epithelium and stromal layers in
      stem cell treated eyes, which showed more epithelial layers and enhanced wound
      healing performance of Ki67, E-Cadherin, and alpha-SMA. Our study shows the
      potential clinical and histological advantages in the topical ADSC treatment for
      corneal lesions in mice.

PMID- 29206193
TI  - Every OGT Is Illuminated ... by Fluorescent and Synchrotron Lights.
AB  - O6-DNA-alkyl-guanine-DNA-alkyl-transferases (OGTs) are evolutionarily conserved,
      unique proteins that repair alkylation lesions in DNA in a single step reaction.
      Alkylating agents are environmental pollutants as well as by-products of cellular
      reactions, but are also very effective chemotherapeutic drugs. OGTs are major
      players in counteracting the effects of such agents, thus their action in turn
      affects genome integrity, survival of organisms under challenging conditions and
      response to chemotherapy. Numerous studies on OGTs from eukaryotes, bacteria and
      archaea have been reported, highlighting amazing features that make OGTs unique
      proteins in their reaction mechanism as well as post-reaction fate. This review
      reports recent functional and structural data on two prokaryotic OGTs, from the
      pathogenic bacterium Mycobacterium tuberculosis and the hyperthermophilic
      archaeon Sulfolobus solfataricus, respectively. These studies provided insight in
      the role of OGTs in the biology of these microorganisms, but also important hints
      useful to understand the general properties of this class of proteins.

PMID- 29206195
TI  - Psychological Distress and Zika, Dengue and Chikungunya Symptoms Following the
      2016 Earthquake in Bahia de Caraquez, Ecuador.
AB  - On 16 April 2016, a 7.8 magnitude earthquake struck coastal Ecuador, resulting in
      significant mortality and morbidity, damages to infrastructure, and psychological
      trauma. This event coincided with the first outbreak of Zika virus (ZIKV) and co
      circulation with dengue virus (DENV) and chikungunya virus (CHIKV). We tested
      whether the degree of psychological distress was associated with the presence of
      suspected DENV, CHIKV, ZIKV (DCZ) infections three months after the earthquake.
      In July 2016, 601 household members from four communities in Bahia de Caraquez,
      Manabi Province, Ecuador, were surveyed in a post-disaster health evaluation.
      Information was collected on demographics, physical damages and injuries, chronic
      diseases, self-reported psychological distress, and DCZ symptoms. We calculated
      the prevalence of arbovirus and distress symptoms by community. ANOVA was used to
      compare the mean number of psychological distress symptoms between people with
      versus without suspected DCZ infections by age, gender, community and the need to
      sleep outside of the home due to damages. The prevalence of suspected DCZ
      infections was 9.7% and the prevalence of psychological distress was 58.1%. The
      average number of psychological distress symptoms was significantly higher among
      people with suspected DCZ infections in the periurban community of Bella Vista,
      in women, in adults 40-64 years of age and in individuals not sleeping at home (p
      < 0.05). The results of this study highlight the need to investigate the
      interactions between psychological distress and arboviral infections following
      natural disasters.

PMID- 29206197
TI  - Associations between Urinary Phthalate Metabolites and Serum Anti-Muller Hormone
      Levels in U.S. Men Based on National Health and Nutrition Examination Survey 2003
      2004.
AB  - Anti-Muller hormone (AMH) plays an important role in reproductive development and
      has a wide potential clinical application value. Phthalates have been widely
      found in human living environment and have negative effects on human
      reproduction. This study aimed to explore the relationship between urinary
      phthalate metabolites and serum AMH level in the general male population. Cross
      sectional analyses were performed with a population of 489 men aged more than 12
      years who participated in National Health and Nutrition Examination Survey
      (NHANES) 2003-2004 by Centers for Disease Control and Prevention, the United
      States. NHANES public data (demographic and socioeconomic information,
      examinations, and laboratory tests) were analyzed using Kruskal-Wallis test,
      Wilcoxon test and multivariable regression. Results showed that the urine
      concentration of mono (3-carboxypropyl) phthalate (MCPP) of 12-20 age group was
      significantly positively correlated with serum AMH concentration in the model
      without any covariates (p < 0.05). In the 60-year-old group, the monomethyl
      phthalate (MEP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations
      were significantly correlated with serum AMH concentrations in models both with
      and without covariates (all p < 0.05). It could be concluded that exposure to
      phthalates might have negative effects on AMH level, especially in seniors. AMH
      could be used as a marker of exposure to phthalates in aged males. How exposure
      to phthalates affected AMH level and what the potential long-term health
      consequences of their relationship are needs more investigation.

PMID- 29206198
TI  - Genome-Wide Comprehensive Analysis the Molecular Phylogenetic Evaluation and
      Tissue-Specific Expression of SABATH Gene Family in Salvia miltiorrhiza.
AB  - The plant SABATH gene family is a group of O-methyltransferases (O-MTs), which
      belongs to the S-adenosyl-l-methionine-dependent methyltransferases (SAM-MTs).
      The resulting reaction products of SABATH genes play an important role in various
      processes of plant development. In this study, a total of 30 SABATH genes were
      detected in Salvia miltiorrhiza, which is an important medicinal plant, widely
      used to treat cardiovascular disease. Multiple sequence alignment and
      phylogenetic analyses showed that SmSABATH genes could be classified into three
      groups. The ratios of non-synonymous (Ka) and synonymous (Ks) substitution rates
      of 11 pairs paralogous of SmSABATH genes revealed that the SmSABATH genes had
      gone through purifying selection. Positive selection analyses using site models
      and branch-site models indicated that SmSABATH genes had undergone selective
      pressure for adaptive evolution. Functional divergence analyses suggested that
      the SmSABATH subgroup genes were divergent in terms of functions and positive
      selection sites that contributed to a functional divergence among the subgroups
      that were detected. Tissue-specific expression showed that the SABATH gene family
      in S. miltiorrhiza was primarily expressed in stems and leaves.

PMID- 29206196
TI  - The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and
      Implications in Health and Disease.
AB  - Among the chaperones and co-chaperones regulating the glucocorticoid receptor
      (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across
      different disciplines. This review provides an update on the role of the
      different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The
      development leading to the focus on FKBP51 is outlined. Further, a survey of the
      vast literature on the mechanism and function of FKBP51 is provided. This
      includes its structure and biochemical function, its regulation on different
      levels-transcription, post-transcription, and post-translation-and its function
      in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein
      organizing protein complexes rather than a chaperone contributing to the folding
      of individual proteins is collated. Finally, FKBP51's involvement in physiology
      and disease is outlined, and the promising efforts in developing drugs targeting
      FKBP51 are discussed.

PMID- 29206199
TI  - A Novel Receptor Tyrosine Kinase Switch Promotes Gastrointestinal Stromal Tumor
      Drug Resistance.
AB  - The fact that most gastrointestinal stromal tumors (GISTs) acquire resistance to
      imatinib (IM)-based targeted therapy remains the main driving force to identify
      novel molecular targets that are capable to increase GISTs sensitivity to the
      current therapeutic regimens. Secondary resistance to IM in GISTs typically
      occurs due to several mechanisms that include hemi- or homo-zygous deletion of
      the wild-type KIT allele, overexpression of focal adhesion kinase (FAK) and
      insulin-like growth factor receptor I (IGF-1R) amplification, BRAF mutation, a
      RTK switch (loss of c-KIT and gain of c-MET/AXL), etc. We established and
      characterized the IM-resistant GIST T-1 cell line (GIST T-1R) lacking secondary c
      KIT mutations typical for the IM-resistant phenotype. The resistance to IM in
      GIST T-1R cells was due to RTK switch (loss of c-KIT/gain of FGFR2alpha). Indeed,
      we have found that FGFR inhibition reduced cellular viability, induced apoptosis
      and affected the growth kinetics of the IM-resistant GISTs in vitro. In contrast,
      IM-naive GIST T-1 parental cells were not susceptible to FGFR inhibition.
      Importantly, inhibition of FGF-signaling restored the susceptibility to IM in IM
      resistant GISTs. Additionally, IM-resistant GISTs were less susceptible to
      certain chemotherapeutic agents as compared to parental IM-sensitive GIST cells.
      The chemoresistance in GIST T-1R cells is not due to overexpression of ABC
      related transporter proteins and might be the result of upregulation of DNA
      damage signaling and repair (DDR) genes involved in DNA double-strand break (DSB)
      repair pathways (e.g., XRCC3, Rad51, etc.). Taken together, the established GIST
      T-1R cell subline might be used for in vitro and in vivo studies to examine the
      efficacy and prospective use of FGFR inhibitors for patients with IM-resistant,
      un-resectable and metastatic forms of GISTs with the type of RTK switch indicated
      above.

PMID- 29206200
TI  - l-Glutamine Attenuates Apoptosis Induced by Endoplasmic Reticulum Stress by
      Activating the IRE1alpha-XBP1 Axis in IPEC-J2: A Novel Mechanism of l-Glutamine
      in Promoting Intestinal Health.
AB  - Intestinal absorption and barrier malfunctions are associated with endoplasmic
      reticulum stress (ERS) in the intestine. We induced ERS by exposing the
      intestinal porcine epithelial cell line J2 (IPEC-J2) to tunicamycin (TUNI) to
      explore the potential of l-glutamine to reduce ERS-induced apoptosis. Our
      experiments demonstrated that exposing cells to TUNI results in spontaneous ERS
      and encourages the upregulation of glucose-regulated protein 78 (GRP78).
      Prolonged TUNI-induced ERS was found to increase apoptosis mediated by C/enhancer
      binding protein homologous protein (CHOP), accompanied by GRP78 downregulation.
      Treatment with l-glutamine was found to promote cell proliferation within the
      growth medium but to have little effect in basic Dulbecco's modified Eagle
      medium. Finally, in the milieu of TUNI-induced ERS, l-glutamine was found to
      maintain a high level of GRP78, alleviate CHOP-mediated apoptosis and activate
      the inositol requiring enzyme 1alpha (IRE1alpha)-X-box binding protein 1 (XBP1)
      axis. A specific inhibitor of the IRE1alpha-XBP1 axis reversed the protective
      effect of l-glutamine by blocking the expression of IRE1alpha/XBP1s. We propose
      that the functional effect of l-glutamine on intestinal health may be partly due
      to its modulation of ERS and CHOP-mediated apoptosis.

PMID- 29206201
TI  - Selection on the Major Color Gene Melanocortin-1-Receptor Shaped the Evolution of
      the Melanocortin System Genes.
AB  - Modular genetic systems and networks have complex evolutionary histories shaped
      by selection acting on single genes as well as on their integrated function
      within the network. However, uncovering molecular coevolution requires the
      detection of coevolving sites in sequences. Detailed knowledge of the functions
      of each gene in the system is also necessary to identify the selective agents
      driving coevolution. Using recently developed computational tools, we
      investigated the effect of positive selection on the coevolution of ten major
      genes in the melanocortin system, responsible for multiple physiological
      functions and human diseases. Substitutions driven by positive selection at the
      melanocortin-1-receptor (MC1R) induced more coevolutionary changes on the system
      than positive selection on other genes in the system. Contrarily, selection on
      the highly pleiotropic POMC gene, which orchestrates the activation of the
      different melanocortin receptors, had the lowest coevolutionary influence. MC1R
      and possibly its main function, melanin pigmentation, seems to have influenced
      the evolution of the melanocortin system more than functions regulated by MC2-5Rs
      such as energy homeostasis, glucocorticoid-dependent stress and anti-inflammatory
      responses. Although replication in other regulatory systems is needed, this
      suggests that single functional aspects of a genetic network or system can be of
      higher importance than others in shaping coevolution among the genes that
      integrate it.

PMID- 29206202
TI  - Bioconverted Orostachys japonicas Extracts Suppress Angiogenic Activity of Ms-1
      Endothelial Cells.
AB  - Orostachys japonicus A. Berger (), known as Wa-song in Korea, has been reported
      to exert various biological effects, such as anti-tumor, anti-oxidant, and anti
      febrile effects. However, the anti-angiogenic effects of O.japonicus extracts
      remain to be investigated. In the present study, we demonstrated the anti
      angiogenic effects of bioconverted O. japonicus extract (BOE) in Ms-1 mouse
      endothelial cells and compared them with the bioactivities of O. japonicus
      extract (OE). BOE, but not OE, were found to exert anti-angiogenic effects,
      including inhibition of cell migration, cell adhesion, tube formation of Ms-1
      cells, and blood vessel formation of matrigel plug assay in vivo. Furthermore,
      protein levels of phosphorylated Src kinase were lower in BOE-treated cells than
      in OE-treated cells. Treatment with OE or BOE did not influence cell viability
      during the experimental period. Bioconverted extract of O.japonicus have anti
      angiogenic effects in vitro and vivo, but non-bioconverted extract do not. We
      suggest that these observed anti-angiogenic effects are caused by the changes in
      the composition of bioactive compounds in the extracts as a result of biological
      conversion.

PMID- 29206203
TI  - De Novo RNA Sequencing and Expression Analysis of Aconitum carmichaelii to
      Analyze Key Genes Involved in the Biosynthesis of Diterpene Alkaloids.
AB  - Aconitum carmichaelii is an important medicinal herb used widely in China, Japan,
      India, Korea, and other Asian countries. While extensive research on the
      characterization of metabolic extracts of A. carmichaelii has shown accumulation
      of numerous bioactive metabolites including aconitine and aconitine-type
      diterpene alkaloids, its biosynthetic pathway remains largely unknown.
      Biosynthesis of these secondary metabolites is tightly controlled and mostly
      occurs in a tissue-specific manner; therefore, transcriptome analysis across
      multiple tissues is an attractive method to identify the molecular components
      involved for further functional characterization. In order to understand the
      biosynthesis of secondary metabolites, Illumina-based deep transcriptome
      profiling and analysis was performed for four tissues (flower, bud, leaf, and
      root) of A. carmichaelii, resulting in 5.5 Gbps clean RNA-seq reads assembled
      into 128,183 unigenes. Unigenes annotated as possible rate-determining steps of
      an aconitine-type biosynthetic pathway were highly expressed in the root, in
      accordance with previous reports describing the root as the accumulation site for
      these metabolites. We also identified 21 unigenes annotated as cytochrome P450s
      and highly expressed in roots, which represent candidate unigenes involved in the
      diversification of secondary metabolites. Comparative transcriptome analysis of
      A. carmichaelii with A. heterophyllum identified 20,232 orthogroups, representing
      30,633 unigenes of A. carmichaelii, gene ontology enrichment analysis of which
      revealed essential biological process together with a secondary metabolic process
      to be highly enriched. Unigenes identified in this study are strong candidates
      for aconitine-type diterpene alkaloid biosynthesis, and will serve as useful
      resources for further validation studies.

PMID- 29206205
TI  - An All-Glass Microfluidic Network with Integrated Amorphous Silicon Photosensors
      for on-Chip Monitoring of Enzymatic Biochemical Assay.
AB  - A lab-on-chip system, integrating an all-glass microfluidics and on-chip optical
      detection, was developed and tested. The microfluidic network is etched in a
      glass substrate, which is then sealed with a glass cover by direct bonding. Thin
      film amorphous silicon photosensors have been fabricated on the sealed
      microfluidic substrate preventing the contamination of the micro-channels. The
      microfluidic network is then made accessible by opening inlets and outlets just
      prior to the use, ensuring the sterility of the device. The entire fabrication
      process relies on conventional photolithographic microfabrication techniques and
      is suitable for low-cost mass production of the device. The lab-on-chip system
      has been tested by implementing a chemiluminescent biochemical reaction. The
      inner channel walls of the microfluidic network are chemically functionalized
      with a layer of polymer brushes and horseradish peroxidase is immobilized into
      the coated channel. The results demonstrate the successful on-chip detection of
      hydrogen peroxide down to 18 MUM by using luminol and 4-iodophenol as enhancer
      agent.

PMID- 29206206
TI  - Anneal-Hardening Behavior of Cr-Fe-C Alloy Deposits Prepared in a Cr3+-Based Bath
      with Fe2+ Ions.
AB  - Cr-Fe-C alloy deposits were successfully prepared on high-carbon tool steel in a
      Cr3+-based electroplating bath containing Fe2+ ions and suitable complex agents.
      A Cr-based alloy deposit was obtained with an electroplating current density
      higher than 25 Adm-2, and a Fe-based alloy deposit was obtained using a current
      density of 20 Adm-2. Following electroplating, these alloy deposited specimens
      were annealed via rapid thermal annealing (RTA) at 500  degrees C for different
      periods up to 30 s. The experimental results show that Cr- and Fe-based alloy
      deposits could be significantly hardened after RTA at 500  degrees C for a few
      seconds. The maximum hardness was that of the Cr-Fe-C alloy deposit annealed at
      500  degrees C for 10 s. The maximum hardness of 1205 Hv was detected from the
      annealed Cr-based alloy deposit prepared with 30 ASD. The hardening mechanism of
      annealed Cr- and Fe-based alloy deposits is attributed to the precipitation of C
      related membranes. The hardness values of the annealed Cr- and Fe-based alloy
      deposits increase with the increasing degree of crystallization of the C-related
      membranes.

PMID- 29206204
TI  - Antioxidants Protect against Arsenic Induced Mitochondrial Cardio-Toxicity.
AB  - Arsenic is a potent cardiovascular toxicant associated with numerous biomarkers
      of cardiovascular diseases in exposed human populations. Arsenic is also a
      carcinogen, yet arsenic trioxide is used as a therapeutic agent in the treatment
      of acute promyelotic leukemia (APL). The therapeutic use of arsenic is limited
      due to its severe cardiovascular side effects. Many of the toxic effects of
      arsenic are mediated by mitochondrial dysfunction and related to arsenic's effect
      on oxidative stress. Therefore, we investigated the effectiveness of antioxidants
      against arsenic induced cardiovascular dysfunction. A growing body of evidence
      suggests that antioxidant phytonutrients may ameliorate the toxic effects of
      arsenic on mitochondria by scavenging free radicals. This review identifies 21
      antioxidants that can effectively reverse mitochondrial dysfunction and oxidative
      stress in cardiovascular cells and tissues. In addition, we propose that
      antioxidants have the potential to improve the cardiovascular health of millions
      of people chronically exposed to elevated arsenic concentrations through
      contaminated water supplies or used to treat certain types of leukemias.
      Importantly, we identify conceptual gaps in research and development of new mito
      protective antioxidants and suggest avenues for future research to improve
      bioavailability of antioxidants and distribution to target tissues in order
      reduce arsenic-induced cardiovascular toxicity in a real-world context.

PMID- 29206207
TI  - Terpenoids from Octocorals of the Genus Pachyclavularia.
AB  - In this paper, we reviewed natural compounds isolated from octocorals belonging
      to the genus Pachyclavularia, including 20 cembrane-, 39 briarane-, and eight
      briarellin-related diterpenoids, and one secosterol. The chemical constituents of
      these 68 secondary metabolites, and their names, structures, and bioactivities,
      along with studies of their biological activities, are summarized in this review.
      Based on the literature, many of these compounds possess bioactivities, including
      anti-inflammation properties, cytotoxicity, and ichthyotoxicity, suggesting that
      they may have the potential to be developed into biomedical agents for treatment.

PMID- 29206208
TI  - A RNA-Seq Analysis of the Response of Photosynthetic System to Low Nitrogen
      Supply in Maize Leaf.
AB  - Nitrogen is a major limiting factor for crop productivity. The relationship
      between photosynthesis and nitrogen nutrition has been widely studied. However,
      the molecular response of leaf photosynthesis to low nitrogen supply in crops is
      less clear. In this study, RNA sequencing technology (RNA-Seq) was used to
      investigate the gene expressions related to photosynthesis in maize in response
      to low nitrogen supply. It was found that low nitrogen supply down-regulated the
      expression of genes involved in photosystem I (PSI) and photosystem II (PSII).
      Thus, low nitrogen supply down-regulated the expression of genes related to the
      antenna system, reduced light absorption, light transport, and electron
      transport. Correspondingly, the parameters related to chlorophyll fluorescence
      were very sensitive to nitrogen deficiency. Under low nitrogen supply, leaf
      chlorophyll content, actual quantum yield of PSII photochemistry, photochemical
      quenching, and electron transport rate, were reduced. However, the thermal
      diffusion and chlorophyll fluorescence were increased. RNA-Seq was used to
      analyze the genes involved in the response of leaf photosynthesis to low nitrogen
      supply in maize. These results highlight the possibility of utilizing chlorophyll
      fluorescence parameters, and the related genes, as indicators for plant nitrogen
      nutrition. This could lead to the development of new tools to make precise
      nitrogen fertilizer recommendations and select nitrogen-efficient genotypes.

PMID- 29206209
TI  - Dioscorea quinqueloba Ameliorates Oxazolone- and 2,4-Dinitrochlorobenzene-induced
      Atopic Dermatitis Symptoms in Murine Models.
AB  - Dioscorea quinqueloba has been used for food substances, as well as in herbal
      medicines for allergic diseases such as asthma. This study aimed to investigate
      the anti-atopic dermatitis (AD) effects of the total extract of D. quinqueloba
      rhizomes and active fractionson murine oxazolone- and 2,4-dinitrochlorobenzene
      induced models of AD. Specific AD symptoms, such as erythema, ear swelling, and
      epidermis thickening, were significantly reduced in the oxazolone-mediated AD
      BALB/c mice upon topical application of D. quinqueloba rhizomes 95% EtOH extract
      (DQ). DQEA (D. quinqueloba rhizomes EtOAc fraction) was beneficial for protecting
      the skin barrier against AD in DNCB-sensitized SKH-1 hairless mice. Decreased
      total serum IgE and IL-4 levels could be observed in atopic dorsal skin samples
      of the DQEA-treated group. On the basis of the phytochemical analysis, DQEA was
      found to contain dioscin and gracillin as its main compounds. Therapeutic
      applications with D. quinqueloba might be useful in the treatment of AD and
      related inflammatory skin diseases.

PMID- 29206210
TI  - Immortalization of Porcine 11beta-Hydroxysteroid Dehydrogenase Type 1-Transgenic
      Liver Cells Using SV40 Large T Antigen.
AB  - Cortisol is a steroid hormone essential to the maintenance of homeostasis that is
      released in response to stress and low blood glucose concentration. Cortisol is
      converted from cortisone by 11betahydroxysteroid dehydrogenase type 1 (HSD11B1).
      It has been reported that too much cortisol or overexpression of HSD11B1 induces
      obesity and the insulin resistance that accompanies metabolic syndrome in rodent
      adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were
      established, and a porcine model was generated by SCNT using those fibroblasts.
      Hepatocytes overexpressing HSD11B1 were obtained from livers of this porcine
      model and cultured in vitro. However, the primary hepatocytes were found to have
      a short life span or low proliferation rate. To overcome these problems, the SV40
      large T antigen was transduced into primary HSD11B1-TG hepatocytes, and those
      cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored
      morphology, more rapid proliferation rate, and more expression of HSD11B1 than
      primary hepatocytes. As well, these cells kept the hepatic characteristics such
      as gluconeogenic response to cortisone and increased expression of hepatic
      makers. The immortalized HSD11B1-TG hepatocytes may be useful for studying traits
      and potential therapeutic drugs for treatment of metabolic disorders induced by
      overexpression of HSD11B1.

PMID- 29206211
TI  - The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel
      Disease: A Comprehensive Review and Future Therapeutic Perspectives.
AB  - Eating habits have changed dramatically over the years, leading to an imbalance
      in the ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in favour of n-6
      PUFAs, particularly in the Western diet. Meanwhile, the incidence of inflammatory
      bowel disease (IBD) is increasing worldwide. Recent epidemiological data indicate
      the potential beneficial effect of n-3 PUFAs in ulcerative colitis (UC)
      prevention, whereas consumption of a higher ratio of n-6 PUFAs versus n-3 PUFAs
      has been associated with an increased UC incidence. The long-chain dietary n-3
      PUFAs are the major components of n-3 fish oil and have been shown to have anti
      inflammatory properties in several chronic inflammatory disorders, being involved
      in the regulation of immunological and inflammatory responses. Despite
      experimental evidence implying biological plausibility, clinical data are still
      controversial, especially in Crohn's disease. Clinical trials of fish-oil
      derivatives in IBD have produced mixed results, showing beneficial effects, but
      failing to demonstrate a clear protective effect in preventing clinical relapse.
      Such data are insufficient to make a recommendation for the use of n-3 PUFAs in
      clinical practice. Here, we present the findings of a comprehensive literature
      search on the role of n-3 PUFAs in IBD development and treatment, and highlight
      new therapeutic perspectives.

PMID- 29206212
TI  - Quartz Crystal Microbalance Electronic Interfacing Systems: A Review.
AB  - Quartz Crystal Microbalance (QCM) sensors are actively being implemented in
      various fields due to their compatibility with different operating conditions in
      gaseous/liquid mediums for a wide range of measurements. This trend has been
      matched by the parallel advancement in tailored electronic interfacing systems
      for QCM sensors. That is, selecting the appropriate electronic circuit is vital
      for accurate sensor measurements. Many techniques were developed over time to
      cover the expanding measurement requirements (e.g., accommodating highly-damping
      environments). This paper presents a comprehensive review of the various existing
      QCM electronic interfacing systems. Namely, impedance-based analysis, oscillators
      (conventional and lock-in based techniques), exponential decay methods and the
      emerging phase-mass based characterization. The aforementioned methods are
      discussed in detail and qualitatively compared in terms of their performance for
      various applications. In addition, some theoretical improvements and
      recommendations are introduced for adequate systems implementation. Finally,
      specific design considerations of high-temperature microbalance systems (e.g.,
      GaPO4 crystals (GCM) and Langasite crystals (LCM)) are introduced, while
      assessing their overall system performance, stability and quality compared to
      conventional low-temperature applications.

PMID- 29206213
TI  - Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal
      Neuron Hyperexcitability in Rodents.
AB  - Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral
      neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and
      norepinephrine, and is shown to be effective against pain. However, whether and
      how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not
      clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal;
      i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and
      von Frey filament tests, respectively. When significant allodynic signs were
      observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were
      injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced
      the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular
      recording method, we further confirmed that 30 mg/kg of duloxetine could
      significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR)
      cells. The anti-allodynic effect of duloxetine was completely blocked by an
      intrathecal injection of phentolamine (non-selective alpha-adrenergic receptor
      antagonist, 20 MUg), or prazosin (alpha1-adrenergic receptor antagonists, 10
      MUg); however, idazoxan (alpha2-adrenergic receptor antagonist, 10 MUg) did not
      block it. In conclusion, we suggest that duloxetine may have an effective
      protective action against oxaliplatin-induced neuropathic pain and spinal
      hyperexcitability, which is mediated by spinal alpha1-adrenergic receptors.

PMID- 29206215
TI  - Dynamic Spectrum Access for Internet of Things Service in Cognitive Radio-Enabled
      LPWANs.
AB  - In this paper, we focus on a dynamic spectrum access strategy for Internet of
      Things (IoT) applications in two types of radio systems: cellular networks and
      cognitive radio-enabled low power wide area networks (CR-LPWANs). The spectrum
      channel contention between the licensed cellular networks and the unlicensed CR
      LPWANs, which work with them, only takes place within the cellular radio spectrum
      range. Our aim is to maximize the spectrum capacity for the unlicensed users
      while ensuring that it never interferes with the licensed network. Therefore, in
      this paper we propose a dynamic spectrum access strategy for CR-LPWANs operating
      in both licensed and unlicensed bands. The simulation and the numerical analysis
      by using a matrix geometric approach for the strategy are presented. Finally, we
      obtain the blocking probability of the licensed users, the mean dwell time of the
      unlicensed user, and the total carried traffic and combined service quality for
      the licensed and unlicensed users. The results show that the proposed strategy
      can maximize the spectrum capacity for the unlicensed users using IoT
      applications as well as keep the service quality of the licensed users
      independent of them.

PMID- 29206214
TI  - Immunotherapy for Prostate Cancer: Where We Are Headed.
AB  - Prostate cancer is one of the most common malignant neoplasms in men worldwide,
      and is the fifth cause of cancer-related death. In recent years, a new generation
      of therapies have been approved for the management of metastatic disease.
      Moreover, the development of new immunotherapeutic drugs has become a novel
      frontier for the treatment of several tumor types; to date, numerous studies have
      investigated their potential activity, including in prostate cancer. In this
      article, we discuss the role of emerging immunotherapeutic drugs in prostate
      cancer patients.

PMID- 29206217
TI  - Synthesis of a Novel Polyethoxysilsesquiazane and Thermal Conversion into Ternary
      Silicon Oxynitride Ceramics with Enhanced Thermal Stability.
AB  - A novel polyethoxysilsesquiazane ([EtOSi(NH)1.5]n, EtOSZ) was synthesized by
      ammonolysis at -78  degrees C of ethoxytrichlorosilane (EtOSiCl3), which was
      isolated by distillation as a reaction product of SiCl4 and EtOH. Attenuated
      total reflection-infra red (ATR-IR), 13C-, and 29Si-nuclear magnetic resonance
      (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection
      of Si-NH-Si linkage and EtO group. The simultaneous thermogravimetric and mass
      spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen
      carbon bond of the EtO group to evolve ethylene as a main gaseous species formed
      in-situ, which lead to the formation at 800  degrees C of quaternary amorphous Si
      C-N with an extremely low carbon content (1.1 wt %) when compared to the
      theoretical EtOSZ (25.1 wt %). Subsequent heat treatment up to 1400  degrees C in
      N2 lead to the formation of X-ray amorphous ternary Si-O-N. Further heating to
      1600  degrees C in N2 promoted crystallization and phase partitioning to afford
      Si2N2O nanocrystallites identified by the XRD and TEM analyses. The thermal
      stability up to 1400  degrees C of the amorphous state achieved for the ternary
      Si-O-N was further studied by chemical composition analysis, as well as X-ray
      photoelectron spectroscopy (XPS) and 29Si-NMR spectroscopic analyses, and the
      results were discussed aiming to develop a novel polymeric precursor for ternary
      amorphous Si-O-N ceramics with an enhanced thermal stability.

PMID- 29206216
TI  - Bioactive Steroids and Saponins of the Genus Trillium.
AB  - The species of the genus Trillium (Melanthiaceae alt. Trilliaceae) include
      perennial herbs with characteristic rhizomes mainly distributed in Asia and North
      America. Steroids and saponins are the main classes of phytochemicals present in
      these plants. This review summarizes and discusses the current knowledge on their
      chemistry, as well as the in vitro and in vivo studies carried out on the
      extracts, fractions and isolated pure compounds from the different species
      belonging to this genus, focusing on core biological properties, i.e., cytotoxic,
      antifungal and anti-inflammatory activities.

PMID- 29206218
TI  - Mountain hare transcriptome and diagnostic markers as resources to monitor
      hybridization with European hares.
AB  - We report the first mountain hare (Lepus timidus) transcriptome, produced by de
      novo assembly of RNA-sequencing reads. Data were obtained from eight specimens
      sampled in two localities, Alps and Ireland. The mountain hare tends to be
      replaced by the invading European hare (Lepus europaeus) in their numerous
      contact zones where the species hybridize, which affects their gene pool to a yet
      unquantified degree. We characterize and annotate the mountain hare
      transcriptome, detect polymorphism in the two analysed populations and use
      previously published data on the European hare (three specimens, representing the
      European lineage of the species) to identify 4 672 putative diagnostic sites
      between the species. A subset of 85 random independent SNPs was successfully
      validated using PCR and Sanger sequencing. These valuable genomic resources can
      be used to design tools to assess population status and monitor hybridization
      between species.

PMID- 29206219
TI  - Long-term monitoring of coral reef fish assemblages in the Western central
      pacific.
AB  - Throughout the tropics, coral reef ecosystems, which are critically important to
      people, have been greatly altered by humans. Differentiating human impacts from
      natural drivers of ecosystem state is essential to effective management. Here we
      present a dataset from a large-scale monitoring program that surveys coral reef
      fish assemblages and habitats encompassing the bulk of the US-affiliated tropical
      Pacific, and spanning wide gradients in both natural drivers and human impact.
      Currently, this includes >5,500 surveys from 39 islands and atolls in Hawaii
      (including the main and Northwestern Hawaiian Islands) and affiliated geo
      political regions of American Samoa, the Commonwealth of the Northern Mariana
      Islands, Guam, and the Pacific Remote Islands Areas. The dataset spans 2010-2017,
      during which time, each region was visited at least every three years, and ~500
      1,000 surveys performed annually. This standardised dataset is a powerful
      resource that can be used to understand how human, environmental and
      oceanographic conditions influence coral reef fish community structure and
      function, providing a basis for research to support effective management
      outcomes.

PMID- 29206220
TI  - MatchingLand, geospatial data testbed for the assessment of matching methods.
AB  - This article presents datasets prepared with the aim of helping the evaluation of
      geospatial matching methods for vector data. These datasets were built up from
      mapping data produced by official Spanish mapping agencies. The testbed supplied
      encompasses the three geometry types: point, line and area. Initial datasets were
      submitted to geometric transformations in order to generate synthetic datasets.
      These transformations represent factors that might influence the performance of
      geospatial matching methods, like the morphology of linear or areal features,
      systematic transformations, and random disturbance over initial data. We call our
      11 GiB benchmark data 'MatchingLand' and we hope it can be useful for the
      geographic information science research community.

PMID- 29206221
TI  - Corrigendum: Transcriptomic profiling of 39 commonly-used neuroblastoma cell
      lines.
AB  - This corrects the article DOI: 10.1038/sdata.2017.33.

PMID- 29206222
TI  - Corrigendum: The Coral Trait Database, a curated database of trait information
      for coral species from the global oceans.
AB  - This corrects the article DOI: 10.1038/sdata.2016.17.

PMID- 29206223
TI  - A model of the onset of the senescence associated secretory phenotype after DNA
      damage induced senescence.
AB  - Cells and tissues are exposed to stress from numerous sources. Senescence is a
      protective mechanism that prevents malignant tissue changes and constitutes a
      fundamental mechanism of aging. It can be accompanied by a senescence associated
      secretory phenotype (SASP) that causes chronic inflammation. We present a Boolean
      network model-based gene regulatory network of the SASP, incorporating published
      gene interaction data. The simulation results describe current biological
      knowledge. The model predicts different in-silico knockouts that prevent key SASP
      mediators, IL-6 and IL-8, from getting activated upon DNA damage. The NF-kappaB
      Essential Modulator (NEMO) was the most promising in-silico knockout candidate
      and we were able to show its importance in the inhibition of IL-6 and IL-8
      following DNA-damage in murine dermal fibroblasts in-vitro. We strengthen the
      speculated regulator function of the NF-kappaB signaling pathway in the onset and
      maintenance of the SASP using in-silico and in-vitro approaches. We were able to
      mechanistically show, that DNA damage mediated SASP triggering of IL-6 and IL-8
      is mainly relayed through NF-kappaB, giving access to possible therapy targets
      for SASP-accompanied diseases.

PMID- 29206224
TI  - Efficient encoding of motion is mediated by gap junctions in the fly visual
      system.
AB  - Understanding the computational implications of specific synaptic connectivity
      patterns is a fundamental goal in neuroscience. In particular, the computational
      role of ubiquitous electrical synapses operating via gap junctions remains
      elusive. In the fly visual system, the cells in the vertical-system network,
      which play a key role in visual processing, primarily connect to each other via
      axonal gap junctions. This network therefore provides a unique opportunity to
      explore the functional role of gap junctions in sensory information processing.
      Our information theoretical analysis of a realistic VS network model shows that
      within 10 ms following the onset of the visual input, the presence of axonal gap
      junctions enables the VS system to efficiently encode the axis of rotation,
      theta, of the fly's ego motion. This encoding efficiency, measured in bits, is
      near-optimal with respect to the physical limits of performance determined by the
      statistical structure of the visual input itself. The VS network is known to be
      connected to downstream pathways via a subset of triplets of the vertical system
      cells; we found that because of the axonal gap junctions, the efficiency of this
      subpopulation in encoding theta is superior to that of the whole vertical system
      network and is robust to a wide range of signal to noise ratios. We further
      demonstrate that this efficient encoding of motion by this subpopulation is
      necessary for the fly's visually guided behavior, such as banked turns in evasive
      maneuvers. Because gap junctions are formed among the axons of the vertical
      system cells, they only impact the system's readout, while maintaining the
      dendritic input intact, suggesting that the computational principles implemented
      by neural circuitries may be much richer than previously appreciated based on
      point neuron models. Our study provides new insights as to how specific network
      connectivity leads to efficient encoding of sensory stimuli.

PMID- 29206225
TI  - Task relevance modulates the behavioural and neural effects of sensory
      predictions.
AB  - The brain is thought to generate internal predictions to optimize behaviour.
      However, it is unclear whether predictions signalling is an automatic brain
      function or depends on task demands. Here, we manipulated the spatial/temporal
      predictability of visual targets, and the relevance of spatial/temporal
      information provided by auditory cues. We used magnetoencephalography (MEG) to
      measure participants' brain activity during task performance. Task relevance
      modulated the influence of predictions on behaviour: spatial/temporal
      predictability improved spatial/temporal discrimination accuracy, but not vice
      versa. To explain these effects, we used behavioural responses to estimate
      subjective predictions under an ideal-observer model. Model-based time-series of
      predictions and prediction errors (PEs) were associated with dissociable neural
      responses: predictions correlated with cue-induced beta-band activity in auditory
      regions and alpha-band activity in visual regions, while stimulus-bound PEs
      correlated with gamma-band activity in posterior regions. Crucially, task
      relevance modulated these spectral correlates, suggesting that current goals
      influence PE and prediction signalling.

PMID- 29206226
TI  - Merging FT-IR and NGS for simultaneous phenotypic and genotypic identification of
      pathogenic Candida species.
AB  - The rapid and accurate identification of pathogen yeast species is crucial for
      clinical diagnosis due to the high level of mortality and morbidity induced, even
      after antifungal therapy. For this purpose, new rapid, high-throughput and
      reliable identification methods are required. In this work we described a
      combined approach based on two high-throughput techniques in order to improve the
      identification of pathogenic yeast strains. Next Generation Sequencing (NGS) of
      ITS and D1/D2 LSU marker regions together with FTIR spectroscopy were applied to
      identify 256 strains belonging to Candida genus isolated in nosocomial
      environments. Multivariate data analysis (MVA) was carried out on NGS and FT-IR
      data-sets, separately. Strains of Candida albicans, C. parapsilosis, C. glabrata
      and C. tropicalis, were identified with high-throughput NGS sequencing of ITS and
      LSU markers and then with FTIR. Inter- and intra-species variability was
      investigated by consensus principal component analysis (CPCA) which combines high
      dimensional data of the two complementary analytical approaches in concatenated
      PCA blocks normalized to the same weight. The total percentage of correct
      identification reached around 97.4% for C. albicans and 74% for C. parapsilosis
      while the other two species showed lower identification rates. Results suggested
      that the identification success increases with the increasing number of strains
      actually used in the PLS analysis. The absence of reliable FT-IR libraries in the
      current scenario is the major limitation in FTIR-based identification of strains,
      although this metabolomics fingerprint represents a valid and affordable aid to
      rapid and high-throughput to clinical diagnosis. According to our data, FT-IR
      libraries should include some tens of certified strains per species, possibly
      over 50, deriving from diverse sources and collected over an extensive time
      period. This implies a multidisciplinary effort of specialists working in strain
      isolation and maintenance, molecular taxonomy, FT-IR technique and chemo-metrics,
      data management and data basing.

PMID- 29206227
TI  - Slam protein dictates subcellular localization and translation of its own mRNA.
AB  - Many mRNAs specifically localize within the cytoplasm and are present in RNA
      protein complexes. It is generally assumed that localization and complex
      formation of these RNAs are controlled by trans-acting proteins encoded by genes
      different than the RNAs themselves. Here, we analyze slow as molasses (slam) mRNA
      that prominently colocalizes with its encoded protein at the basal cortical
      compartment during cellularization. The functional implications of this striking
      colocalization have been unknown. Here, we show that slam mRNA translation is
      spatiotemporally controlled. We found that translation was largely restricted to
      the onset of cellularization when Slam protein levels at the basal domain sharply
      increase. slam mRNA was translated locally, at least partially, as not yet
      translated mRNA transiently accumulated at the basal region. Slam RNA accumulated
      at the basal domain only if Slam protein was present. Furthermore, a slam RNA
      with impaired localization but full coding capacity was only weakly translated.
      We detected a biochemical interaction of slam mRNA and protein as demonstrated by
      specific co-immunoprecipitation from embryonic lysate. The intimate relationship
      of slam mRNA and protein may constitute a positive feedback loop that facilitates
      and controls timely and rapid accumulation of Slam protein at the prospective
      basal region.

PMID- 29206228
TI  - Spatial relationships between above-ground biomass and bird species biodiversity
      in Palawan, Philippines.
AB  - This study maps distribution and spatial congruence between Above-Ground Biomass
      (AGB) and species richness of IUCN listed conservation-dependent and endemic
      avian fauna in Palawan, Philippines. Grey Level Co-Occurrence Texture Matrices
      (GLCMs) extracted from Landsat and ALOS-PALSAR were used in conjunction with
      local field data to model and map local-scale field AGB using the Random Forest
      algorithm (r = 0.92 and RMSE = 31.33 Mg.ha-1). A support vector regression (SVR)
      model was used to identify the factors influencing variation in avian species
      richness at a 1km scale. AGB is one of the most important determinants of avian
      species richness for the study area. Topographic factors and anthropogenic
      factors such as distance from the roads were also found to strongly influence
      avian species richness. Hotspots of high AGB and high species richness
      concentration were mapped using hotspot analysis and the overlaps between areas
      of high AGB and avian species richness was calculated. Results show that the
      overlaps between areas of high AGB with high IUCN red listed avian species
      richness and endemic avian species richness were fairly limited at 13% and 8% at
      the 1-km scale. The overlap between 1) low AGB and low IUCN richness, and 2) low
      AGB and low endemic avian species richness was higher at 36% and 12%
      respectively. The enhanced capacity to spatially map the correlation between AGB
      and avian species richness distribution will further assist the conservation and
      protection of forest areas and threatened avian species.

PMID- 29206229
TI  - pSSAlib: The partial-propensity stochastic chemical network simulator.
AB  - Chemical reaction networks are ubiquitous in biology, and their dynamics is
      fundamentally stochastic. Here, we present the software library pSSAlib, which
      provides a complete and concise implementation of the most efficient partial
      propensity methods for simulating exact stochastic chemical kinetics. pSSAlib can
      import models encoded in Systems Biology Markup Language, supports time delays in
      chemical reactions, and stochastic spatiotemporal reaction-diffusion systems. It
      also provides tools for statistical analysis of simulation results and supports
      multiple output formats. It has previously been used for studies of biochemical
      reaction pathways and to benchmark other stochastic simulation methods. Here, we
      describe pSSAlib in detail and apply it to a new model of the endocytic pathway
      in eukaryotic cells, leading to the discovery of a stochastic counterpart of the
      cut-out switch motif underlying early-to-late endosome conversion. pSSAlib is
      provided as a stand-alone command-line tool and as a developer API. We also
      provide a plug-in for the SBMLToolbox. The open-source code and pre-packaged
      installers are freely available from http://mosaic.mpi-cbg.de.

PMID- 29206230
TI  - Decisional balance and processes of change in community-recruited with moderate
      high versus mild severity of cannabis dependence.
AB  - Decisional Balance and Processes of Change are generally addressed in
      motivational interventions for the treatment of cannabis use disorders. However,
      specific aspects of these multifaceted constructs, with greater relevance for
      severe cannabis users, need to be ascertained to enable better interventions.
      This study aimed to compare the different facets of decisional balance and
      processes of change between mild and severe cannabis users in a community-based
      sample of young undergraduates. Thirty-one severe cannabis users and 31 mild
      cannabis users, indicated with the Severity of Dependence Scale, were assessed
      using the Decisional Balance Questionnaire (DBQ) and the Processes of Change
      Questionnaire (PCQ). We found that severe cannabis users had higher scores in the
      DBQ dimensions of Utilitarian Gains for the Self, Utilitarian Gains for
      Significant Others, and Self-approval, as well as in the total subscale of Gains
      but not Losses. The group of severe cannabis users also had higher scores in the
      PCQ dimensions of Self-revaluations and Counter-conditioning. Our results
      pinpoint specific dimensions of Decisional Balance and Processes of Change that
      are endorsed by severe cannabis users. This knowledge could be applied to inform
      motivational interventions targeting severe cannabis users.

PMID- 29206232
TI  - Behavioral testing of mice exposed to intermediate frequency magnetic fields
      indicates mild memory impairment.
AB  - Human exposure to intermediate frequency magnetic fields (MF) is increasing due
      to applications like electronic article surveillance systems and induction
      heating cooking hobs. However, limited data is available on their possible health
      effects. The present study assessed behavioral and histopathological consequences
      of exposing mice to 7.5 kHz MF at 12 or 120 MUT for 5 weeks. No effects were
      observed on body weight, spontaneous activity, motor coordination, level of
      anxiety or aggression. In the Morris swim task, mice in the 120 MUT group showed
      less steep learning curve than the other groups, but did not differ from controls
      in their search bias in the probe test. The passive avoidance task indicated a
      clear impairment of memory over 48 h in the 120 MUT group. No effects on
      astroglial activation or neurogenesis were observed in the hippocampus. The mRNA
      expression of brain-derived neurotrophic factor did not change but expression of
      the proinflammatory cytokine tumor necrosis factor alpha mRNA was significantly
      increased in the 120 MUT group. These findings suggest that 7.5 kHz MF exposure
      may lead to mild learning and memory impairment, possibly through an inflammatory
      reaction in the hippocampus.

PMID- 29206231
TI  - Cancer-type dependent expression of CK2 transcripts.
AB  - A multitude of proteins are aberrantly expressed in cancer cells, including the
      oncogenic serine-threonine kinase CK2. In a previous report, we found increases
      in CK2 transcript expression that could explain the increased CK2 protein levels
      found in tumors from lung and bronchus, prostate, breast, colon and rectum,
      ovarian and pancreatic cancers. We also found that, contrary to the current
      notions about CK2, some CK2 transcripts were downregulated in several cancers.
      Here, we investigate all other cancers using Oncomine to determine whether they
      also display significant CK2 transcript dysregulation. As anticipated from our
      previous analysis, we found cancers with all CK2 transcripts upregulated (e.g.
      cervical), and cancers where there was a combination of upregulation and/or
      downregulation of the CK2 transcripts (e.g. sarcoma). Unexpectedly, we found some
      cancers with significant downregulation of all CK2 transcripts (e.g. testicular
      cancer). We also found that, in some cases, CK2 transcript levels were already
      dysregulated in benign lesions (e.g. Barrett's esophagus). We also found that CK2
      transcript upregulation correlated with lower patient survival in most cases
      where data was significant. However, there were two cancer types, glioblastoma
      and renal cell carcinoma, where CK2 transcript upregulation correlated with
      higher survival. Overall, these data show that the expression levels of CK2 genes
      is highly variable in cancers and can lead to different patient outcomes.

PMID- 29206233
TI  - Genome-wide admixture and association study of subclinical atherosclerosis in the
      Women's Interagency HIV Study (WIHS).
AB  - Cardiovascular disease (CVD) is a major comorbidity among HIV-infected
      individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and
      reliable subclinical measure of atherosclerosis and is known to predict CVD. We
      performed genome-wide association (GWA) and admixture analysis among 682 HIV
      positive and 288 HIV-negative Black, non-Hispanic women from the Women's
      Interagency HIV study (WIHS) cohort using a combined and stratified analysis
      approach. We found some suggestive associations but none of the SNPs reached
      genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were
      rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin
      glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin
      delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region
      intergenic to family with sequence similarity 5, member C and regulator of G
      protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most
      significant local European ancestry associations were in the region intergenic to
      the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone
      oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on
      chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor
      6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19
      among HIV-positive women, and in the region intergenic to the SEC23-interacting
      protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP |
      PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of
      previously identified SNP associations with cCIMT were also observed and included
      rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the
      secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report
      several SNPs and gene regions in the GWAS and admixture analysis, some of which
      are common across HIV-positive and HIV-negative women as demonstrated using meta
      analysis, and also across the two analytic approaches (i.e., GWA and admixture).
      These findings suggest that local European ancestry plays an important role in
      genetic associations of cCIMT among black women from WIHS along with other
      environmental factors that are related to CVD and may also be triggered by HIV.
      These findings warrant confirmation in independent samples.

PMID- 29206235
TI  - Hybrid precoding based on matrix-adaptive method for multiuser large-scale
      antenna arrays.
AB  - Massive multiple-input multiple-output (MIMO) is envisioned to offer a
      considerable improvement in capacity, but it has a high cost and the radio
      frequency (RF) chain components have a high power consumption at high frequency.
      To address this problem, a hybrid analog and digital precoding scheme has been
      studied recently, which restricts the number of RF chains to far less than the
      number of antenna elements. In this paper, we consider the downlink communication
      of a massive multiuser multiple-input single-output (MU-MISO) system and propose
      an iterative hybrid precoding algorithm to approach the capacity performance of
      the traditional full digital precoding scheme. We aim to attain a large baseband
      gain by zero-forcing (ZF) digital precoding on the equivalent channel and then
      minimize the total power to obtain the optimal RF precoder. Simulation results
      show that the proposed method can approach the performance of the conventional
      fully digital precoding with a low computational complexity.

PMID- 29206234
TI  - Markers of epithelial-to-mesenchymal transition reflect tumor biology according
      to patient age and Gleason score in prostate cancer.
AB  - INTRODUCTION: Prostate carcinoma (PRAD) is one of the most frequently diagnosed
      malignancies amongst men worldwide. It is well-known that androgen receptor (AR)
      plays a pivotal role in a vast majority of prostate tumors. However, recent
      evidence emerged stating that estrogen receptors (ERs) may also contribute to
      prostate tumor development. Moreover, progression and aggressiveness of prostate
      cancer may be associated with differential expression genes of epithelial-to
      mesenchymal transition (EMT). Therefore we aimed to assess the significance of
      receptors status as well as EMT marker genes expression among PRAD patients in
      accordance to their age and Gleason score. MATERIALS AND METHODS: We analyzed
      TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes
      involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical
      characteristic of cancer patients. Then patients were divided into four groups
      according to their age and 5 groups according to Gleason score. Next, we
      evaluated PRAD samples according to relationship between the set of variables in
      different combinations and compared differential expression in subsequent groups
      of patients. The analysis was applied using R packages: FactoMineR, gplots,
      RColorBrewer and NMF. RESULTS: MFA analysis resulted in distinct grouping of PRAD
      patients into four age categories according to expression level of AR, ESR1 and
      ESR2 with the most distinct group of age less than 50 years old. Further
      investigations indicated opposite expression profiles of EMT markers between
      different age groups as well as strong association of EMT gene expression with
      Gleason score. We found that depending on age of prostate cancer patients and
      Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19,
      MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3. CONCLUSIONS: Our major observation
      is that prostate cancer from patients under 50 years old compared to older ones
      has entirely different EMT gene expression profiles showing potentially more
      aggressive invasive phenotype, despite Gleason score classification.

PMID- 29206236
TI  - Structural basis for the substrate selectivity of Helicobacter pylori NucT
      nuclease activity.
AB  - The Phospholipase D (PLD) superfamily of proteins includes a group of enzymes
      with nuclease activity on various nucleic acid substrates. Here, with the aim of
      better understanding the substrate specificity determinants in this subfamily, we
      have characterised the enzymatic activity and the crystal structure of NucT, a
      nuclease implicated in Helicobacter pylori purine salvage and natural
      transformation and compared them to those of its bacterial and mammalian
      homologues. NucT exhibits an endonuclease activity with a strong preference for
      single stranded nucleic acids substrates. We identified histidine124 as essential
      for the catalytic activity of the protein. Comparison of the NucT crystal
      structure at 1.58 A resolution reported here with those of other members of the
      sub-family suggests that the specificity of NucT for single-stranded nucleic
      acids is provided by the width of a positively charged groove giving access to
      the catalytic site.

PMID- 29206237
TI  - One year follow-up after a randomized controlled trial of a 130 g/day low
      carbohydrate diet in patients with type 2 diabetes mellitus and poor glycemic
      control.
AB  - BACKGROUND & AIMS: Recently, we conducted a prospective randomized controlled
      trial (RCT) showing that a 6-month 130g/day low-carbohydrate diet (LCD) reduced
      HbA1c and BMI more than a calorie restricted diet (CRD). [1] To assess whether
      the benefits of the LCD persisted after the intensive intervention, we compared
      HbA1c and BMI between the LCD and CRD groups at 1 year after the end of the 6
      month RCT. METHODS: Following the end of the 6-month RCT, patients were allowed
      to manage their own diets with periodic outpatient visits. One year later, we
      analyzed clinical and nutrition data. RESULTS: Of the 66 participants in the
      original study, 27 in the CRD group and 22 in the LCD group completed this trial.
      One year after the end of the original RCT, the carbohydrate intake was
      comparable between the groups (215 [189-243]/day in the CRD group and 214 (176
      262) g/day in the LCD group). Compared with the baseline data, HbA1c and BMI were
      decreased in both groups (CRD: HbA1c -0.4 [-0.9 to 0.3] % and BMI -0.63 [-1.20 to
      0.18] kg/m2; LCD: HbA1c -0.35 [-1.0 to 0.35] % and BMI -0.77 [-1.15 to -0.12]
      kg/m2). There were no significant differences in HbA1c and BMI between the
      groups. CONCLUSIONS: One year after the diet therapy intervention, the beneficial
      effect of the LCD on reduction of HbA1c and BMI did not persist in comparison
      with CRD. However, combining the data of both groups, significant improvements in
      HbA1c and BMI from baseline were observed. Although the superiority of the LCD
      disappeared 1 year after the intensive intervention, these data suggest that well
      constructed nutrition therapy programs, both CRD and LCD, were equally effective
      in improving HbA1c for at least 1 year. TRIAL REGISTRATION: University Hospital
      Medical Information Network (UMIN) ID000010663.

PMID- 29206238
TI  - Site-level progression of periodontal disease during a follow-up period.
AB  - Periodontal disease is assessed and its progression is determined via
      observations on a site-by-site basis. Periodontal data are complex and structured
      in multiple levels; thus, applying a summary statistical approach (i.e., the
      mean) for site-level evaluations results in loss of information. Previous studies
      have shown the availability of mixed effects modeling. However, clinically
      beneficial information on the progression of periodontal disease during the
      follow-up period is not available. We conducted a multicenter prospective cohort
      study. Using mixed effects modeling, we analyzed 18,834 sites distributed on
      3,139 teeth in 124 patients, and data were collected 5 times over a 24-month
      follow-up period. The change in the clinical attachment level (CAL) was used as
      the outcome variable. The CAL at baseline was an important determinant of the CAL
      changes, which varied widely according to the tooth surface. The salivary levels
      of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter
      actinomycetemcomitans, were affected by CAL progression. "Linear"- and "burst"
      type patterns of CAL progression occurred simultaneously within the same patient.
      More than half of the teeth that presented burst-type progression sites also
      presented linear-type progression sites, and most of the progressions were of the
      linear type. Maxillary premolars and anterior teeth tended to show burst-type
      progression. The parameters identified in this study may guide practitioners in
      determining the type and extent of treatment needed at the site and patient
      levels. In addition, these results show that prior hypotheses concerning "burst"
      and "linear" theories are not valid.

PMID- 29206239
TI  - Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and
      peripheral blood mononuclear cells.
AB  - Triggers of the autoimmune response that leads to type 1 diabetes (T1D) remain
      poorly understood. A possibility is that parallel changes in both T cells and
      target cells provoke autoimmune attack. We previously documented greater Ca2+
      transients in fibroblasts from T1D subjects than non-T1D after exposure to fatty
      acids (FA) and tumor necrosis factor alpha (TNFalpha). These data indicate that
      metabolic and signal transduction defects present in T1D can be elicited ex vivo
      in isolated cells. Changes that precede T1D, including inflammation, may activate
      atypical responses in people that are genetically predisposed to T1D. To identify
      such cellular differences in T1D, we quantified a panel of metabolic responses in
      fibroblasts and peripheral blood cells (PBMCs) from age-matched T1D and non-T1D
      subjects, as models for non-immune and immune cells, respectively. Fibroblasts
      from T1D subjects accumulated more lipid, had higher LC-CoA levels and converted
      more FA to CO2, with less mitochondrial proton leak in response to oleate alone
      or with TNFalpha, using the latter as a model of inflammation. T1D-PBMCs
      contained and also accumulated more lipid following FA exposure. In addition,
      they formed more peroxidized lipid than controls following FA exposure. We
      conclude that both immune and non-immune cells in T1D subjects differ from
      controls in terms of responses to FA and TNFalpha. Our results suggest a
      differential sensitivity to inflammatory insults and FA that may precede and
      contribute to T1D by priming both immune cells and their targets for autoimmune
      reactions.

PMID- 29206241
TI  - Corrigendum: Differential Regulation of Thyroid Hormone Metabolism Target Genes
      during Non-thyroidal Illness Syndrome Triggered by Fasting or Sepsis in Adult
      Mice.
AB  - [This corrects the article on p. 828 in vol. 8, PMID: 29118715.].

PMID- 29206240
TI  - Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on
      the target hierarchy and function of subdominant CD8+ T cells.
AB  - Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal
      ganglia (TG) is associated with a persistent immune infiltrate that includes
      effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6
      mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+
      T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while
      the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant
      epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout
      latency, while non-gB-CD8s exhibit varying degrees of functional compromise. To
      understand how dominance hierarchies relate to CD8+ T cell function during
      latency, we characterized the TG-associated CD8+ T cells following corneal
      infection with a recombinant HSV-1 lacking the immunodominant gB498-505 epitope
      (S1L). S1L induced a numerically equivalent CD8+ T cell infiltrate in the TG that
      was HSV-specific, but lacked specificity for gB498-505. Instead, there was a
      general increase of non-gB-CD8s with specific subdominant epitopes arising to
      codominance. In a latent S1L infection, non-gB-CD8s in the TG showed a hierarchy
      targeting different epitopes at latency compared to at acute times, and these
      cells retained an increased functionality at latency. In a latent S1L infection,
      these non-gB-CD8s also display an equivalent ability to block HSV reactivation in
      ex vivo ganglionic cultures compared to TG infected with wild type HSV-1. These
      data indicate that loss of the immunodominant gB498-505 epitope alters the
      dominance hierarchy and reduces functional compromise of CD8+ T cells specific
      for subdominant HSV-1 epitopes during viral latency.

PMID- 29206242
TI  - Corrigendum: The Diversity of Sequence and Chromosomal Distribution of New
      Transposable Element-Related Segments in the Rye Genome Revealed by FISH and
      Lineage Annotation.
AB  - [This corrects the article on p. 1706 in vol. 8, PMID: 29046683.].

PMID- 29206243
TI  - Corrigendum: Novel Peripherally Restricted Cannabinoid 1 Receptor Selective
      Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese
      Mice.
AB  - [This corrects the article on p. 707 in vol. 8, PMID: 29051736.].

PMID- 29206244
TI  - Corrigendum: Glycemia Is Related to Impaired Cerebrovascular Autoregulation after
      Severe Pediatric Traumatic Brain Injury: A Retrospective Observational Study.
AB  - [This corrects the article on p. 205 in vol. 5, PMID: 28993802.].

PMID- 29206245
TI  - Correction: Liu et al., Dynamics of GnRH Neuron Ionotropic GABA and Glutamate
      Synaptic Receptors Are Unchanged during Estrogen Positive and Negative Feedback
      in Female Mice (eNeuro September/October 2017, 4(5) e0259-17.2017 1-14
      http://dx.doi.org/10.1523/ENEURO.0259-17.2017).
AB  - [This corrects the article DOI: 10.1523/ENEURO.0259-17.2017.][This corrects the
      article DOI: 10.1523/ENEURO.0259-17.2017.].

PMID- 29206246
TI  - Corrigendum: Foot Placement Characteristics and Plantar Pressure Distribution
      Patterns during Stepping on Ground in Neonates.
AB  - [This corrects the article on p. 784 in vol. 8, PMID: 29066982.].

PMID- 29206247
TI  - Erratum: Rare case of conus medullaris glioblastoma multiforme in a teenager.
AB  - [This corrects the article on p. 234 in vol. 8, PMID: 29026670.].

PMID- 29206248
TI  - Corrigendum: Dose-Dependent and Lasting Influences of Intranasal Vasopressin on
      Face Processing in Men.
AB  - [This corrects the article on p. 220 in vol. 8, PMID: 29018407.].

PMID- 29206249
TI  - Facile formation of mesoporous structured mixed-phase (anatase/rutile) TiO2 with
      enhanced visible light photocatalytic activity.
AB  - A new mixed-phase (anatase/rutile) TiO2 with mesoporous structures and smaller
      crystal size (3-5 nm) was successfully synthesized by a facile sol-gel method at
      a lower calcination temperature (100  degrees C). Rhodamine B can be completely
      decomposed in the presence of the as-synthesized nanocomposite after only 60
      minutes under visible light. Therefore it is believed to be a promising candidate
      for wastewater treatment.

PMID- 29206250
TI  - Sequential energy transfer followed by electron transfer in a BODIPY
      bisstyrylBODIPY bound to C60 triad via a 'two-point' binding strategy.
AB  - Excitation transfer from 1BODIPY* to bisstyrylBODIPY followed by electron
      transfer to C60 leading to a charge separated state of appreciable lifetime in a
      supramolecularly assembled triad is demonstrated, as a mimic of the
      photosynthetic 'antenna-reaction centre'.

PMID- 29206251
TI  - Synthesis and characterization of AgGaS2 nanoparticles: a study of growth and
      fluorescence.
AB  - Silver gallium sulfide nanocrystals were synthesized and characterized by
      fluorescence, TEM, EDS, and XRD to better understand the material system with an
      ideal band gap of 2.7 eV. The crystals were found to nucleate in the monoclinic
      structure, and develop two fluorescence peaks (650, 460 nm) influenced by
      stoichiometry.

PMID- 29206252
TI  - Two mixed-addenda Nb/W polyoxometalate-based hybrid compounds containing
      multicopper units: synthesis, structures, and electrochemical and magnetic
      properties.
AB  - Two mixed-addenda Nb/W polyoxometalate (POM)-based hybrid compounds, [CuICu(MU3
      OH)(H2O)6(trz)3]2(PW9Nb3O40).13H2O (1) and [CuICu(MU3
      OH)(H2O)4(Htrz)(trz)3]2(PW9Nb3O40).13H2O (2), were synthesized under hydrothermal
      conditions. Single-crystal X-ray diffraction revealed that compound 1 contains
      planar triangular tricopper {Cu(MU3-OH)(trz)3} units, and these tricopper units
      link to each other to form a 1D anti-parallel chain. CuI ions connect the 1D
      chains by the coordination of trz ligands to form 2D layers in the ab plane.
      Compound 2 contains the same tricopper {Cu(MU3-OH)(trz)3} units as well as
      bicopper {Cu(Htrz)2} units. The tricopper units also form 1D chains and the
      bicopper units connect the 1D chains to form similar 2D layers and finally
      construct the 3D framework. In both compounds, each Nb/W mixed-addenda Keggin
      {PW9Nb3O40} unit links eight tricopper units to generate the final 3D structure.
      Magnetism studies indicate anti-ferromagnetic exchange interactions among the
      CuII ions within the tricopper units, with JCu-Cu values of -209.3 and -200.8 cm
      1 in 1 and 2, respectively.

PMID- 29206253
TI  - Floating rGO-based black membranes for solar driven sterilization.
AB  - This paper presents a new steam sterilization approach that uses a solar-driven
      evaporation system at the water/air interface. Compared to the conventional solar
      autoclave, this new steam sterilization approach via interfacial evaporation
      requires no complex system design to bear high steam pressure. In such a system,
      a reduced graphene oxide/polytetrafluoroethylene composite membrane floating at
      the water/air interface serves as a light-to-heat conversion medium to harvest
      and convert incident solar light into localized heat. Such localized heat raises
      the temperature of the membrane substantially and helps generate steam with a
      temperature higher than 120  degrees C. A sterilization device that takes
      advantage of the interfacial solar-driven evaporation system was built and its
      successful sterilization capability was demonstrated through both chemical and
      biological sterilization tests. The interfacial evaporation-based solar driven
      sterilization approach offers a potential low cost solution to meet the need for
      sterilization in undeveloped areas that lack electrical power but have ample
      solar radiation.

PMID- 29206254
TI  - Curcumin as a functional food-derived factor: degradation products, metabolites,
      bioactivity, and future perspectives.
AB  - Curcumin is a polyphenol found in turmeric (Curcuma longa), used as a spice, in
      food coloring, and as a traditional herbal medicine. It has been shown that
      curcumin has health benefits such as antioxidant, anti-inflammatory, and
      anticancer properties, improvement of brain function, and control of obesity and
      diabetes. However, native curcumin easily degrades and has low oral
      bioavailability, and a recent report has expressed doubt about curcumin's various
      effects. To overcome its low bioavailability, various curcumin formulations with
      enhanced bioavailability are currently being developed. This review discusses the
      chemistry, metabolism, and absorption of curcumin, to which various reported
      health benefits have been ascribed, as well as curcumin's degradation products
      and metabolites and their possible functions. Moreover, the research trend
      towards the obesity- and diabetes-preventing/suppressing aspects of curcumin and
      the latest case studies on highly water-dispersible and bioavailable curcumin
      formulations will be discussed. We summarize the challenges concerning research
      on curcumin's health benefits as follows: clarifying the relationship between
      curcumin's health benefits and the formation of curcumin-derived oxidation and
      degradation products and metabolites, determining whether curcumin itself or
      other components in turmeric are responsible for its effects, and conducting
      further human trials in which multiple research groups employ the same samples
      and conditions. High-bioavailability formulations would be useful in such future
      studies.

PMID- 29206255
TI  - First principles investigation of tunnel FETs based on nanoribbons from
      topological two-dimensional materials.
AB  - We explore nanoribbons from topological two-dimensional stanene as a channel
      material in tunnel field effect transistors. This novel technological option
      offers the possibility of building pure one-dimensional (1D) channel devices
      (comprised of a 1D chain of atoms) due to localized states placed at the
      nanoribbon edges. The investigation is based on first-principles calculations and
      multi-scale transport simulations to assess the performance of devices against
      industry requirements and their robustness with respect to technological issues
      like line edge roughness, detrimental for nanoribbons. We will show that edge
      states are robust with respect to the presence of non-idealities (e.g., atom
      vacancies at the edges), and that 1D-channel TFETs exhibit interesting potential
      for digital applications and room for optimization in order to improve the
      ION/IOFF at the levels required by the ITRS, while opening a path for the
      exploration of new device concepts at the ultimate scaling limits.

PMID- 29206256
TI  - Chiral reagents in glycosylation and modification of carbohydrates.
AB  - Carbohydrates play a significant role in numerous biological events, and the
      chemical synthesis of carbohydrates is vital for further studies to understand
      their various biological functions. Due to the structural complexity of
      carbohydrates, the stereoselective formation of glycosidic linkages and the site
      selective modification of hydroxyl groups are very challenging and at the same
      time extremely important. In recent years, the rapid development of chiral
      reagents including both chiral auxiliaries and chiral catalysts has significantly
      improved the stereoselectivity for glycosylation reactions and the site
      selectivity for the modification of carbohydrates. These new tools will greatly
      facilitate the efficient synthesis of oligosaccharides, polysaccharides, and
      glycoconjugates. In this tutorial review, we will summarize these advances and
      highlight the most recent examples.

PMID- 29206257
TI  - Role of surface adsorption in tuning the properties of black phosphorus.
AB  - H2O and O2 are believed to be key factors that influence the structural stability
      of black phosphorus (BP) in ambient conditions. In this work, the interactions of
      H2O and/or O2 with BP are investigated using first-principles calculations. The
      results indicate that water molecules prefer to adsorb on the BP surface and form
      a six-member water ring. The dissociation barrier of O2 is significantly reduced
      in the presence of H2O, which dramatically promotes the degradation of BP.
      Moreover, the introduction of O2 also facilitates the adsorption of water on the
      surface. The effects of H2O and/or O2 on the quasiparticle band gap and exciton
      binding energy of BP are also investigated. The results suggest that water
      adsorption has only a slight influence on the electronic properties and exciton
      binding energy, while O2 adsorption causes obvious changes in the properties of
      BP, which results in a direct-to-indirect band gap transition in BP.

PMID- 29206259
TI  - Nurse Educators: Leading Health Care to the Quadruple Aim Sweet Spot.

PMID- 29206260
TI  - Faculty and Student Incivility in Undergraduate Nursing Education: An Integrative
      Review.
AB  - BACKGROUND: Incivility is a critical issue in undergraduate nursing education.
      Uncivil acts in academia are increasing and have the potential to affect future
      nursing practice and patient safety outcomes. METHOD: An integrative literature
      review was completed to describe faculty-to-student and student-to-faculty
      incivility in undergraduate nursing education. RESULTS: Seventeen studies were
      included in the review. Four themes emerged from the data: (a) Detrimental to
      Health and Well-Being, (b) Disruption to the Teaching-Learning Environment, (c)
      Stress as a Catalyst, and (d) Incivility Incites Incivility. CONCLUSION: The
      results support data that incivility has harmful physical and psychological
      effects on both faculty and students, and also disturbs the teaching-learning
      environment. Causes of un-civil acts have been highlighted to provide groundwork
      for schools of nursing to implement strategies for mitigating incivility. [J Nurs
      Educ. 2017;56(12):709-716.].

PMID- 29206258
TI  - In vitro inhibition of pancreatic alpha-amylase by spherical and polygonal starch
      nanoparticles.
AB  - Nanoparticles are novel and fascinating materials for tuning the activities of
      enzymes. In this study, we investigated the influence of spherical and polygonal
      starch nanoparticles (SNPs) on alpha-amylase activity and revealed the reaction
      mechanisms by ultraviolet-visible spectrophotometry, fluorescence spectroscopy,
      and circular dichroism (CD) spectroscopy. We discovered that both spherical and
      polygonal SNPs could inhibit the alpha-amylase activity, with half-inhibitory
      concentration values of 0.304 and 0.019 mg mL-1, respectively. Furthermore,
      spherical and polygonal SNPs followed competitive and mixed competitive
      inhibition mechanisms, respectively. The fluorescence data indicated that static
      quenching was dominant in the interaction between SNPs and alpha-amylase. The CD
      results demonstrated that the inhibition of alpha-amylase by SNPs was accompanied
      by the decreased intensity of the CD spectra of alpha-amylase. Our findings
      provide a novel strategy to inhibit alpha-amylase to reduce the digestion of
      starch, thus managing blood glucose levels.

PMID- 29206261
TI  - Internet-Generation Nursing Students' View of Technology-Based Health Care.
AB  - BACKGROUND: Today's nursing school applicants are considered "digital natives."
      This study investigated students' views of new health care technologies. METHOD:
      In a cross-sectional survey among first-year nursing students, 23 common nursing
      activities and five telehealth nursing activities were presented along with three
      statements: "I consider this a core task of nursing," "I look forward to becoming
      trained in this task," and "I think I will do very well in performing this task."
      RESULTS: Internet-generation nursing students (n = 1,113) reported a
      significantly (p ? .001) less positive view of telehealth activities than of
      common nursing activities. Median differences were 0.7 (effect size [ES], -0.54),
      0.4 (ES, -0.48), and 0.3 (ES, -0.39), measured on a 7-point scale. CONCLUSION:
      Internet-generation nursing students do not naturally have a positive view of
      technology-based health care provision. The results emphasize that adequate
      technology and telehealth education is still needed for nursing students. [J Nurs
      Educ. 2017;56(12):717-724.].

PMID- 29206262
TI  - SBIRT Education for Nurse Practitioner Students: Integration Into an MSN Program.
AB  - BACKGROUND: Substance use disorders are a major public health problem. As primary
      care providers, nurse practitioners (NPs) must be proficient at screening,
      identifying, and intervening for at-risk patients. Screening, brief intervention,
      and referral to treatment (SBIRT) is a well-established, evidence-based model for
      teaching behavioral health skills to health care providers. It is vital that
      Master of Science in Nursing (MSN)-NP programs incorporate SBIRT into their
      curricula. METHOD: SBIRT content was mapped to 10 courses across an MSN-NP
      program. Methods of integration included readings, lectures, case studies, role
      plays, tutorials, symposia, and test questions, as well as tracking the use of
      SBIRT during clinical preceptorships. RESULTS: A total of 139 online and on
      campus MSN-NP students were trained. Data demonstrate students successfully
      implemented SBIRT in precepted clinical settings. CONCLUSION: This approach
      provides a framework for integrating SBIRT training into MSN-NP curricula. [J
      Nurs Educ. 2017;56(12):725-732.].

PMID- 29206263
TI  - Improving Clinical Nursing Judgment in Prelicensure Students.
AB  - BACKGROUND: Available models for designing the structure of specific simulation
      based learning (SBL) activities need further analysis. METHOD: This retrospective
      study was conducted using independent samples t tests to examine differences in
      mean clinical nursing judgment development scores between students who completed
      a nursing program prior to the introduction of an experiential learning theory
      (ELT)-based simulation design and students who completed the program after the
      adoption of its use for all scenario-based SBL activities. RESULTS: Results
      showed a significant increase in clinical nursing judgment at both the beginning
      and end of a baccalaureate program in which all scenario-based SBL used an ELT
      design. CONCLUSION: Consistency with International Nursing Association for
      Clinical Simulation and Learning standards of best practice and the use of ELT in
      SBL can improve student outcomes by fostering the development of clinical nursing
      judgment. [J Nurs Educ. 2017;56(12):733-736.].

PMID- 29206264
TI  - RN-to-BSN Students' Quality Improvement Knowledge, Skills, Confidence, and
      Systems Thinking.
AB  - BACKGROUND: Little evidence demonstrates that RN-to-baccalaureate nursing (BSN)
      graduates have met The Essentials of Baccalaureate Education for Professional
      Nursing Practice-specifically, evidence of the graduates' organizational and
      systems leadership related to quality care and patient safety. This BSN
      Essentials reflects the QSEN quality improvement (QI) competency. The purpose of
      this pilot study was to develop and test an assessment strategy to measure RN-to
      BSN students' QI competence and their perception of QI knowledge and skills.
      METHOD: Students (N = 59) from six RN-to-BSN programs participated in a Qualtrics
      survey e-mailed during the last semester of their program. RESULTS: The majority
      of students (60%) reported that they did not experience QI content in their
      program. Scores on QI knowledge, skills, and systems thinking were low, yet the
      students self-reported that they were confident in their ability to perform QI.
      CONCLUSION: This pilot study provides an assessment strategy to measure students'
      competence related to QI. Nursing education has an opportunity to integrate and
      measure QI competence to ensure that nurses have the knowledge and skills to
      continually improve patient care. [J Nurs Educ. 2017;56(12):737-740.].

PMID- 29206265
TI  - Students' Perceptions of the Psychological Well-Being of a Transgender Client
      Through Simulation.
AB  - BACKGROUND: The need to address mental health concerns for transgender clients is
      imperative. Nursing curricula must prepare students to provide holistic care for
      individuals within this community. The purpose of this study was to explore
      undergraduate nursing students' experiences providing mental health care for a
      transgender client through simulation. METHOD: Focus group interviews were
      conducted with data analyzed using content analysis. RESULTS: The three
      categories that emerged were limited experience addressing mental health needs,
      intervening with client anxiety with the subcategories of prioritizing care and
      collaboration, and therapeutic nurse-client relationship with the subcategory of
      therapeutic communication. CONCLUSION: Nursing students must be prepared to
      provide holistic care for transgender individuals. Simulation allowed students to
      assess the client and evaluate their therapeutic communication in a safe learning
      environment. Further understanding of mental health care needs of transgender
      clients is essential for the promotion of their well-being. [J Nurs Educ.
      2017;56(12):741-744.].

PMID- 29206266
TI  - Innovative Approach to Senior Practicum Students.
AB  - BACKGROUND: Traditional senior practicum experiences (SPEs) are microsystem based
      they allow senior nursing students the opportunity to build professional nursing
      competencies as they transition into practice. As health care transformation
      continues unabated, there is a need to work toward closing the gap between
      nursing academia and nursing practice. METHOD: A cardiovascular service line
      created an innovative SPE to better prepare senior nursing students for working
      as professional nurses in a service line model. RESULTS: The Senior Practicum
      Immersion Experience (SPIE) proved to be beneficial to senior practicum students
      and offered firsthand experience of the role professional nurses play in a
      service line model. This model increased the number of senior practicum students
      accepted into the cardiac service line by 50%. CONCLUSION: The SPIE creates an
      innovative solution to increasing the number of senior practicum students while
      allowing students the ability to learn and practice in a service line model. [J
      Nurs Educ. 2017;56(12):745-747.].

PMID- 29206267
TI  - Innovative Intraprofessional Clinical Training for Clinical Nurse Specialists and
      Nurse Practitioner Students.
AB  - BACKGROUND: Most graduate nursing education curricula naturally segregate
      students by role as they move into their role-specific coursework and clinical
      experiences. Segregation diminishes the opportunity for students to form
      important intraprofessional relationships. Intraprofessional collaboration can
      potentiate the influence of advanced practice nurses on individual patients,
      patient populations, and larger health care systems. METHOD: This pilot program
      paired clinical nurse specialists and nurse practitioner students in immersion
      clinical practicum experiences aimed to increase their understanding of each
      other's role and potential avenues for collaboration in future practice. RESULTS:
      Students report increased levels of understanding of each other's roles and scope
      of practice. Pairing students in immersion experiences broadens their clinical
      reach and potentiates their influence on vulnerable patient populations.
      CONCLUSION: Findings indicate that this pilot program can be sustained. Benefits
      to early and focused intraprofessional educational experiences include increased
      awareness of advanced practice roles, scope of practice, and potential avenues
      for future collaboration. [J Nurs Educ. 2017;56(12):748-751.].

PMID- 29206268
TI  - Infusing Systems and Quality Improvement Throughout an Undergraduate Nursing
      Curriculum.
AB  - BACKGROUND: Nurse educators are constantly revising curricula to ensure that
      graduating nurses have the requisite skills for today's fast-paced, rapidly
      changing, nonlinear complex care environment. Key nursing education and practice
      organizations identify systems thinking and quality improvement as essential
      skills for nurses at the point of care. METHOD: Systems thinking and quality
      improvement were embedded across a Bachelor of Nursing (BSN) curriculum in a
      manner that does not dislocate other, more traditional content. RESULTS: To date,
      approximately 500 students have been exposed to the new BSN curriculum.
      Sustainable approaches, preliminary results, lessons learned, and recommendations
      for sustainability and replication are discussed. CONCLUSION: Integrating systems
      thinking and quality improvement with traditional content across the entire
      undergraduate curriculum exposes students to increasingly sophisticated real
      world experiences that highlight the relevance and significance of these skills
      in the health care context. Feedback from practice partners suggests this
      approach helps bridge the education and practice gap. [J Nurs Educ.
      2017;56(12):752-757.].

PMID- 29206269
TI  - Tutoring for Success: Empowering Graduate Nurses After Failure on the NCLEX-RN.
AB  - BACKGROUND: Failure on the National Council Licensure Examination for Registered
      Nurses (NCLEX-RN) is a devastating experience. Most research related to NCLEX-RN
      is focused on predicting and preventing failure. Despite these efforts, more than
      20,000 nursing school graduates experience failure on the NCLEX-RN each year, and
      there is a paucity of literature regarding remediation after failure. METHOD: The
      aim of this article is to describe an individualized tutoring approach centered
      on establishing a trusting relationship and incorporating two core strategies for
      remediation: the nugget method, and a six-step strategy for question analysis.
      RESULTS: This individualized tutoring method has been used by three nursing
      faculty with a 95% success rate on an NCLEX retake attempt. CONCLUSION: Further
      research is needed to identify the elements of this tutoring method that
      influence success. [J Nurs Educ. 2017;56(12):758-761.].

PMID- 29206270
TI  - Prevention of Lateral Violence in Nursing Through Education: The Bullying
      Awareness Seminar.

PMID- 29206272
TI  - Comments on: Influence of transcutaneous electrical nerve stimulation on
      spasticity, balance, and walking speed in stroke patients: A systematic review
      and meta-analysis.

PMID- 29206271
TI  - Poetry of Pharmacology.

PMID- 29206273
TI  - Social relationships in rehabilitation and their impact on positive outcomes
      among amputees with lower limb loss at Walter Reed National Military Medical
      Center.
AB  - OBJECTIVE: To explore how the social context of the clinic influenced the way
      former patients with lower limb loss in the Military Advanced Training Center at
      Walter Reed National Military Medical Center evaluated their outcomes. DESIGN:
      Cross-sectional phenomenological-based interviews and observations. PATIENTS:
      Twenty individuals with lower limb amputation were recruited from a
      multidisciplinary military treatment programme for patients with lower-extremity
      traumatic limb-loss injured in Afghanistan or Iraq. METHODS: Lightly structured
      interviews were conducted either in person or over the telephone with former
      patients and clinical care-providers. Where possible, observation was conducted
      in conjunction with the interviews. The research team used content analysis of
      the data, consistent with ethnographic methods. RESULTS: Analysis of the
      therapeutic effect of social relationships developed in the clinical
      rehabilitation programme identified 3 areas of significance: enduring
      relationships with key care-providers, access to treatment team by patients, and
      peer support among patients. CONCLUSION: The social component of service delivery
      influences patients' outcomes from clinical care. These results could be
      translated across healthcare settings to improve patient outcomes.

PMID- 29206275
TI  - Response to 'Phase IV head-to-head randomized controlled trial comparing ingenol
      mebutate 0.015% gel with diclofenac sodium 3% gel for the treatment of actinic
      keratosis on the face or scalp': reply from the authors.

PMID- 29206274
TI  - Predictors of return-to-work in patients with chronic musculoskeletal pain: A
      randomized clinical trial.
AB  - OBJECTIVE: To assess the predictive effect of a multidisciplinary intervention
      programme, pain, work-related factors and health, including anxiety/depression
      and beliefs, on return-to-work for patients sick-listed due to musculoskeletal
      pain. DESIGN: A randomized clinical study. METHODS: A total of 284 patients were
      randomized to either a multidisciplinary intervention programme (n = 141) or to a
      less resource-demanding brief intervention (n = 143). Work participation was
      estimated monthly from register data for 12 months. Return-to-work was defined as
      increased work participation in 3 consecutive months. RESULTS: In the adjusted
      model, return-to-work by 3 months was associated with a multidisciplinary
      intervention programme (odds ratio (OR) = 2.7, 95% confidence interval (95% CI) =
      1.1-6.9), the factor "belief that work was cause of the pain" (OR = 2.2, 95% CI =
      1.1-4.3), anxiety and depression (OR = 0.5, 95% CI = 0.2-0.98), and by an
      interaction between the multidisciplinary intervention and perceived support at
      work (OR = 0.3, 95% CI = 0.1-0.9). At 12 months, only duration of sick leave was
      associated with return-to-work (OR = 0.6, 95% CI = 0.5-0.8). CONCLUSION:
      Multidisciplinary intervention may hasten return-to-work and benefit those who
      perceive low support at work, but at 12 months only duration of sick leave at
      baseline was associated with return-to-work.

PMID- 29206276
TI  - Response to Dr. Olshansky.

PMID- 29206277
TI  - Response to Dr. Clarfield.

PMID- 29206278
TI  - Clinical sequencing: From raw data to diagnosis with lifetime value.
AB  - High-throughput sequencing (HTS) has revolutionized genetics by enabling the
      detection of sequence variants at hitherto unprecedented large scale. Despite
      these advances, however, there are still remaining challenges in the complete
      coverage of targeted regions (genes, exome or genome) as well as in HTS data
      analysis and interpretation. Moreover, it is easy to get overwhelmed by the
      plethora of available methods and tools for HTS. Here, we review the step-by-step
      process from the generation of sequence data to molecular diagnosis of Mendelian
      diseases. Highlighting advantages and limitations, this review addresses the
      current state of (1) HTS technologies, considering targeted, whole-exome, and
      whole-genome sequencing on short- and long-read platforms; (2) read alignment,
      variant calling and interpretation; as well as (3) regulatory issues related to
      genetic counseling, reimbursement, and data storage.

PMID- 29206279
TI  - The risk of breast cancer in BRCA1 and BRCA2 mutation carriers without a first
      degree relative with breast cancer.
AB  - The objective of this study was to estimate the lifetime risk of breast cancer in
      women with a BRCA1 or BRCA2 mutation with and without at least 1 first-degree
      relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation
      were followed. Age- and gene-specific breast cancer rates were calculated. The
      relative risks of breast cancer for subjects with a family history of breast
      cancer, compared to no family history were calculated. The mean age at baseline
      was 41.1 years, and they were followed for a mean of 6.0 years. The estimated
      penetrance of breast cancer to age 80 years was 60.8% for BRCA1 and 63.1% for
      BRCA2. For all BRCA carriers, the penetrance of breast cancer to age 80 for those
      with no first-degree relative with breast cancer was 60.4% and 63.3% for those
      with at least 1 first-degree relative with breast cancer. The risk of breast
      cancer for BRCA carriers with no first-degree relative with breast cancer is
      substantial, and as a result, clinical management for these women should be the
      same as those for women with an affected relative.

PMID- 29206280
TI  - Directional scatter imaging for the stereoscopic tracking of fiducial markers in
      a single kV exposure.
AB  - PURPOSE: To demonstrate, via Monte Carlo simulation, that an image obtained from
      the patient-generated scattered radiation forced to impinge on the detector from
      a known direction by means of parallel-focused grids, can be used to complement
      the information conveyed by the primary image, such that accurate stereoscopic
      three-dimensional localization of fiducial markers can be achieved in a single kV
      x-ray exposure. METHODS: A voxelized Zubal phantom was used to model the process
      of fiducial marker localization. The markers were represented as made of gold and
      cylindrical in shape with dimensions of 5 mm in length and 1 mm in diameter.
      Three such markers were placed in the Zubal phantom at the prostate level. Two
      gantry-mounted image acquisition geometries were modeled: a single kV imaging
      system and a dual kV-MV imaging system. The detector was modeled as a 30 cm * 40
      cm Gd2 O2 S screen with a thickness of 0.2 cm and a resolution of 768 * 1024
      pixels. The PENELOPE Monte Carlo code was used to calculate the absorbed dose in
      this detector imparted by the transmitted primary and directional scatter
      radiation. A grayscale conversion was then applied to obtain an image from which
      the positions of the markers were determined. Two parallel-focused grid
      geometries were modeled, one based on the standard lead-carbon fiber grids and a
      proposed modification using tungsten as the shielding material. Absorbed dose in
      the patient model was also calculated. RESULTS: It is shown that the combination
      of primary and directional scatter images provides the means for an accurate
      stereoscopic fiducial marker 3D localization in a single x-ray exposure, provided
      the antiscatter grids are made thick enough to allow radiation traveling only in
      a particular direction to reach the detector. For the proposed tungsten grid and
      the x-ray spectrum used in this work, grid ratios of 20 and thickness of 0.2 cm,
      provide the necessary shielding while for the standard lead grids, a ratio of at
      least 166 and a thickness of 2 cm are needed to obtain discernible directional
      scatter images. CONCLUSIONS: We have shown that it is in principle possible to
      determine the 3D position of fiducial markers in a single exposure by making use
      of the radiation scattered by the patient to form an image that complements the
      information obtained with the primary beam. The method here proposed requires
      minimal modification of existing clinical hardware.

PMID- 29206281
TI  - Giant cell tumours of bone treated with denosumab: histological,
      immunohistochemical and H3F3A mutation analyses.
AB  - AIMS: Denosumab, a human monoclonal antibody directed against the receptor
      activator of nuclear factor-kappaB ligand (RANKL), is a therapeutic agent for
      giant cell tumour of bone (GCTB). Although some studies have reported that
      denosumab shrinks tumours and induces bone formation, the actual effects of RANKL
      suppression on GCTB remain unclear. A mutation in the H3 histone family member 3A
      gene (H3F3A) was recently identified as a genetic signature for GCTB. The aim of
      this study was to investigate the histopathological features and H3F3A mutation
      status of GCTBs treated with denosumab. METHODS AND RESULTS: Nine biopsy
      diagnosed patients with GCTB, who underwent curettage after neoadjuvant denosumab
      therapy, were reviewed. Immunohistochemistry for NFATc1 (an osteoclast marker),
      RUNX2 (an osteoblast marker) and histone H3.3 G34W (G34W, a GCTB marker) was
      performed; furthermore, H3F3A mutation status was examined with direct
      sequencing. Before therapy, GCTBs comprised NFATc1+ and RUNX2+ cells. All cases
      were G34W+ and contained H3F3A mutations. After therapy, the osteoclast-like
      giant cells disappeared. Areas of slender spindle cell proliferation and
      reticular woven bone that were NFATc1- and RUNX2+ replaced the lesions in various
      proportions. However, all post-therapy lesions still contained many G34W+ cells
      and harboured H3F3A mutations. Immunofluorescence double staining revealed that
      RUNX2+ mononuclear cells coexpressed G34W in pre-therapy and post-therapy
      lesions. Two patients experienced radiologically detected local recurrence within
      2 years. CONCLUSIONS: Denosumab therapy effectively decreases the number of
      osteoclastic cells in GCTBs. However, the neoplastic cells with H3F3A mutation
      survive denosumab treatment and undergo dramatic histological changes in response
      to this agent.

PMID- 29206282
TI  - Hidradenitis and smoking: reply from the authors.

PMID- 29206284
TI  - Healthy Life Expectancy Is Expanding.

PMID- 29206285
TI  - The Future of Health.

PMID- 29206283
TI  - Transposable Element Mediated Innovation in Gene Regulatory Landscapes of Cells:
      Re-Visiting the "Gene-Battery" Model.
AB  - Transposable elements (TEs) are no longer considered to be "junk" DNA. Here, we
      review how TEs can impact gene regulation systematically. TEs encode various
      regulatory elements that enables them to regulate gene expression. RJ Britten and
      EH Davidson hypothesized that TEs can integrate the function of various
      transcriptional regulators into gene regulatory networks. Uniquely TEs can
      deposit regulatory sites across the genome when they transpose, and thereby bring
      multiple genes under control of the same regulatory logic. Several studies
      together have robustly established that TEs participate in embryonic development
      and oncogenesis. We discuss the regulatory characteristics of TEs in context of
      evolution to understand the extent of their impact on gene networks.
      Understanding these features of TEs is central to future investigations of TEs in
      cellular processes and phenotypic presentations, which are applicable to
      development and disease studies. We re-visit the Britten-Davidson "gene-battery"
      model and understand the genetic and transcriptional impact of TEs in innovating
      gene regulatory networks.

PMID- 29206286
TI  - Recognition of Delirium Features in Clinical Practice: Data from the "Delirium
      Day 2015" National Survey.
AB  - BACKGROUND/OBJECTIVES: Delirium is underrecognized in clinical practice. The
      primary aim of the present multicenter study was to compare the ability of nurses
      to identify delirium features with a standardized assessment. The secondary aim
      was to identify predictors of missed or incorrect identifications of delirium by
      nurses. DESIGN: Point prevalence study in 120 wards across Italy. SETTING:
      "Delirium Day 2015." PARTICIPANTS: Inpatients aged 65 and older (N = 1,867).
      MEASUREMENTS: Participants and nurses were asked specific questions to
      investigate their perceptions of the presence of delirium features (acute
      cognitive change, inattention, cognitive fluctuations, impaired arousal).
      Delirium was identified according to the results of the Assessment Test for
      Delirium and Cognitive Impairment (4AT), completed by a physician. Comorbidities
      including dementia, disability, drug treatments, and delirium motor subtype
      according to the Delirium Motor Subtype Scale were recorded. RESULTS: Delirium
      was present in 429 subjects (23%) according to the 4AT. Cognitive fluctuations
      was the delirium feature that the nurses most often recognized. Nurses'
      perceptions of acute cognitive change, cognitive fluctuations, or impaired
      arousal had 84% sensitivity and 81% specificity for delirium. The nonmotor
      subtype of delirium was less likely to be recognized (80%) than the hyperactive
      (97%), mixed (92%), and hypoactive (90%) subtypes. Incorrect perception of
      delirium was more frequent in subjects with dementia (specificity 64%).
      CONCLUSIONS: The delirium feature that nurses were best able to recognize was
      cognitive fluctuations. The nonmotor subtype was associated with a lower
      recognition rate. Routine observation and registration of delirium features by
      nurses in clinical practice might be helpful to increase formal diagnosis of
      delirium.

PMID- 29206287
TI  - High dose-per-pulse electron beam dosimetry: Commissioning of the Oriatron eRT6
      prototype linear accelerator for preclinical use.
AB  - PURPOSE: The Oriatron eRT6 is an experimental high dose-per-pulse linear
      accelerator (linac) which was designed to deliver an electron beam with variable
      dose-rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to
      study the radiobiological effects of high dose-per-pulse/dose-rate electron beam
      irradiation, in the context of preclinical and cognitive studies. In this work,
      we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype
      linac. MATERIALS AND METHODS: The beam was characterized in different steps. The
      output stability was studied by performing repeated measurements over a period of
      20 months. The relative output variations caused by changing beam parameters,
      such as the temporal electron pulse width, the pulse repetition frequency and the
      pulse amplitude were also analyzed. Finally, depth dose curves and field sizes
      were measured for two different beam settings, resulting in one beam with a
      conventional radiotherapy dose-rate and one with a much higher dose-rate.
      Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced
      Markus ionization chamber. In addition, we developed a beam current monitoring
      system based on the signals from an induction torus positioned at the beam exit
      of the waveguide and from a graphite beam collimator. RESULTS: The stability of
      the output over repeated measurements was found to be good, with a standard
      deviation smaller than 1%. However, non-negligible day-to-day variations of the
      beam output were observed. Those output variations showed different trends
      depending on the dose-rate. The analysis of the relative output variation as a
      function of various beam parameters showed that in a given configuration, the
      dose-rate could be reliably varied over three orders of magnitude.
      Interdependence effects on the output variation between the parameters were also
      observed. The beam energy and field size were found to be slightly dose-rate
      dependent and suitable mainly for small animal irradiation. The beam monitoring
      system was able to measure in a reproducible way the total charge of electrons
      that exit the machine, as long as the electron pulse amplitude remains above a
      given threshold. Furthermore, we were able to relate the charge measured with the
      monitoring system to the absorbed dose in a solid water phantom. CONCLUSION: The
      Oriatron eRT6 was successfully commissioned for preclinical use and is currently
      in full operation, with studies being performed on the radiobiological effects of
      high dose-per-pulse irradiation.

PMID- 29206288
TI  - Absorbed dose kernel and self-shielding calculations for a novel radiopaque glass
      microsphere for transarterial radioembolization.
AB  - PURPOSE: Radiopaque microspheres may provide intraprocedural and postprocedural
      feedback during transarterial radioembolization (TARE). Furthermore, the
      potential to use higher resolution x-ray imaging techniques as opposed to nuclear
      medicine imaging suggests that significant improvements in the accuracy and
      precision of radiation dosimetry calculations could be realized for this type of
      therapy. This study investigates the absorbed dose kernel for novel radiopaque
      microspheres including contributions of both short and long-lived contaminant
      radionuclides while concurrently quantifying the self-shielding of the glass
      network. METHODS: Monte Carlo simulations using EGSnrc were performed to
      determine the dose kernels for all monoenergetic electron emissions and all beta
      spectra for radionuclides reported in a neutron activation study of the
      microspheres. Simulations were benchmarked against an accepted 90 Y dose point
      kernel. Self-shielding was quantified for the microspheres by simulating an
      isotropically emitting, uniformly distributed source, in glass and in water. The
      ratio of the absorbed doses was scored as a function of distance from a
      microsphere. The absorbed dose kernel for the microspheres was calculated for (a)
      two bead formulations following (b) two different durations of neutron
      activation, at (c) various time points following activation. RESULTS: Self
      shielding varies with time postremoval from the reactor. At early time points, it
      is less pronounced due to the higher energies of the emissions. It is on the
      order of 0.4-2.8% at a radial distance of 5.43 mm with increased size from 10 to
      50 MUm in diameter during the time that the microspheres would be administered to
      a patient. At long time points, self-shielding is more pronounced and can reach
      values in excess of 20% near the end of the range of the emissions. Absorbed dose
      kernels for 90 Y, 90m Y, 85m Sr, 85 Sr, 87m Sr, 89 Sr, 70 Ga, 72 Ga, and 31 Si
      are presented and used to determine an overall kernel for the microspheres based
      on weighted activities. The shapes of the absorbed dose kernels are dominated at
      short times postactivation by the contributions of 70 Ga and 72 Ga. Following
      decay of the short-lived contaminants, the absorbed dose kernel is effectively
      that of 90 Y. After approximately 1000 h postactivation, the contributions of 85
      Sr and 89 Sr become increasingly dominant, though the absorbed dose-rate around
      the beads drops by roughly four orders of magnitude. CONCLUSIONS: The
      introduction of high atomic number elements for the purpose of increasing
      radiopacity necessarily leads to the production of radionuclides other than 90 Y
      in the microspheres. Most of the radionuclides in this study are short-lived and
      are likely not of any significant concern for this therapeutic agent. The
      presence of small quantities of longer lived radionuclides will change the shape
      of the absorbed dose kernel around a microsphere at long time points
      postadministration when activity levels are significantly reduced.

PMID- 29206289
TI  - Contiguous verrucous proliferations in syringocystadenoma papilliferum: A
      retrospective analysis with additional evaluation via mutation-specific BRAFV600E
      immunohistochemistry.
AB  - BACKGROUND: Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous
      adnexal proliferation. There have been several reports describing collision
      lesions of SCAP and verruca, although little is known about the frequency of this
      association. Molecular testing has revealed the BRAFV600E mutation in a large
      proportion of SCAP cases, although its expression pattern has not been previously
      evaluated. METHODS: In this retrospective analysis, we explored the potential
      histopathological association between verruca and SCAP. We also evaluated
      mutation-specific BRAFV600E expression in these lesions by immunohistochemistry.
      Cases of SCAP diagnosed over a 7-year period were closely reviewed for the
      presence of contiguous verrucous proliferations. Additional sections were cut and
      stained using the BRAFV600E-specific clone VE1 antibody. RESULTS: Contiguous
      verrucous proliferations were identified in 9 out of 12 identified cases.
      Furthermore, expression of the BRAFV600E mutation was identified in 7 out of 12
      cases. Interestingly, in SCAP associated with endophytic verrucous proliferations
      (n = 4), expression of BRAFV600E was found in both the glandular and the
      contiguous hyperplastic squamous epithelium. CONCLUSION: Overall, these findings
      suggest that contiguous verrucous proliferations in SCAP are common. Both
      components of the neoplasm may express the BRAFV600E mutation, which is
      suggestive of a common origin.

PMID- 29206290
TI  - Primary effusion lymphoma in Taiwan shows two distinctive clinicopathological
      subtypes with rare human immunodeficiency virus association.
AB  - AIMS: To investigate the clinicopathological and molecular features of primary
      effusion lymphoma (PEL) in Taiwan and the association with human immunodeficiency
      virus (HIV), human herpesvirus 8 (HHV8) and Epstein-Barr virus (EBV). METHODS AND
      RESULTS: We investigated retrospectively 26 cases with a median age of 76.5. Only
      one (4%) patient was infected with HIV. Cytologically, all lymphoma cells
      revealed typical immunoblastic to plasmablastic morphology.
      Immunohistochemically, HHV8 was positive in eight (32%) tumours and negative in
      17 (68%) cases. All 23 tested cases examined were of the non-germinal-centre B
      cell phenotype. MYC proto-oncogene (MYC) and Epstein-Barr encoding mRNA (EBER)
      were positive in 43% (nine of 21) and 17% (four of 23) cases, respectively.
      Immunoglobulin heavy chain (IGH), B cell lymphoma (BCL)2, BCL6 and MYC were
      rearranged in 71%, 11%, 12% and 18% cases, respectively. By univariate analysis,
      the overall survival (OS) was associated statistically with MYC expression (P =
      0.012) and BCL2 rearrangement (P = 0.035), but not with the others. By
      multivariate analysis, no factor was statistically significant. Compared to the
      HHV8-negative cases, the HHV8-positive cases were mainly of the plasmablastic
      immunophenotype expressing CD30 and CD138, and with a less frequent expression of
      pan-B cell markers. CONCLUSIONS: Apart from the phenotypical difference, our HHV8
      positive neoplasms were not distinct from the HHV8-negative group. Literature
      review of 256 cases, including our cases, revealed that HHV8-positive cases were
      associated more frequently with HIV and EBV infection, with rare MYC
      rearrangement, and a poorer prognosis than HHV8-negative cases. We propose to
      name the HHV8-positive cases as 'classical' or 'type I PEL' and the HHV8-negative
      cases as 'type II PEL', stressing the similarities and the distinctive features
      between these two groups.

PMID- 29206291
TI  - Cranial shape variation in adult howler monkeys (Alouatta seniculus).
AB  - Howler monkeys (genus Alouatta) display a distinctive cranial architecture
      characterized by airorhynchy (or retroflexion of the facial skeleton on the
      cranial base), a small braincase, and a posteriorly oriented foramen magnum. This
      configuration has been associated with distinct factors including a high folivory
      diet, locomotion, and the presence of a specialized vocal tract characterized by
      large hyoid bone. However, the morphological relationships between the facial and
      neurocranial blocks in Alouatta have been scarcely investigated. In this study we
      quantitatively analyzed the cranial shape variation in Alouatta seniculus, to
      evaluate possible influences and constraints in face and braincase associated
      with airorhynchy. We also considered the structural role of the pteric area
      within the cranial functional matrix. We applied landmark-based analysis and
      multivariate statistics to 31 adult crania, computing shape analyses based on 3D
      coordinates registration as well as the analysis of the Euclidean distance matrix
      to investigate patterns of intraspecific morphological variability. Our results
      suggest that allometry is the main source of variation involved in shaping
      cranial morphology in howlers, influencing the degree of facial proportions and
      braincase flattening, and generating the main sexual differences. Larger
      individuals are characterized by a higher degree of airorhynchy, neurocranial
      flattening, and expansion of the zygomatic arch. Allometric variations influence
      the skull as a whole, without distinct patterns for face and braincase, which
      behave as an integrated morphological unit. A preliminary survey on the pteric
      pattern suggests that the morphology of this area may be the result of variations
      in the vertical growth rates between face and braincase. Future studies should be
      dedicated to the ontogenetic series and focus on airorhynchy in terms of
      differential growth among distinct cranial districts.

PMID- 29206292
TI  - MicroRNA-6869-5p acts as a tumor suppressor via targeting TLR4/NF-kappaB
      signaling pathway in colorectal cancer.
AB  - Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play
      important roles in the development and progression of colorectal cancer (CRC).
      However, little is known about the role of a newly identified miRNA, miR-6869-5p,
      in CRC. We aim to investigate the modifying effects and underlying mechanisms of
      miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced
      levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples
      from patients with CRC. The prediction of targets of miR-6869-5p in databases of
      targetscan, microRNA. ORG and miRDBA revealed that toll-like receptor 4 (TLR4) is
      a potential target for this miRNA. MiR-6869-5p could inhibit cell proliferation
      and the production of inflammatory cytokines (TNF-alpha and IL-6) in CRC cells
      via directly targeting TLR4. The protective effect of miR-6869-5p from colorectal
      carcinogenesis was dependent on TLR4/NF-kappaB signaling pathway. In addition,
      the 3-year survival was poor among CRC patients with decreased levels of miR-6869
      5p in serum exosomes. Thus, miR-6869-5p may serve as a tumor suppressor in CRC,
      and serum exosomal miR-6869-5p is a promising circulating biomarker for the
      prediction of CRC prognosis.

PMID- 29206293
TI  - Arbuscular mycorrhizal fungi reduce nitrous oxide emissions from N2 O hotspots.
AB  - Nitrous oxide (N2 O) is a potent, globally important, greenhouse gas,
      predominantly released from agricultural soils during nitrogen (N) cycling.
      Arbuscular mycorrhizal fungi (AMF) form a mutualistic symbiosis with two-thirds
      of land plants, providing phosphorus and/or N in exchange for carbon. As AMF
      acquire N, it was hypothesized that AMF hyphae may reduce N2 O production. AMF
      hyphae were either allowed (AMF) or prevented (nonAMF) access to a compartment
      containing an organic matter and soil patch in two independent microcosm
      experiments. Compartment and patch N2 O production was measured both before and
      after addition of ammonium and nitrate. In both experiments, N2 O production
      decreased when AMF hyphae were present before inorganic N addition. In the
      presence of AMF hyphae, N2 O production remained low following ammonium
      application, but increased in the nonAMF controls. By contrast, negligible N2 O
      was produced following nitrate application to either AMF treatment. Thus, the
      main N2 O source in this system appeared to be via nitrification, and the
      production of N2 O was reduced in the presence of AMF hyphae. It is hypothesized
      that AMF hyphae may be outcompeting slow-growing nitrifiers for ammonium. This
      has significant global implications for our understanding of soil N cycling
      pathways and N2 O production.

PMID- 29206294
TI  - Hormone regulates endometrial function via cooperation of endoplasmic reticulum
      stress and mTOR-autophagy.
AB  - In ruminant, the receptive endometrium and the elongation of the hatched
      blastocyst are required to complete the process of implantation. However, the
      mechanisms regulating goat endometrial function during the peri-implantation
      period of pregnancy are still unclear. In this study, EECs were treated with
      progesterone, estradiol, and interferon-tau (IFNT). We have found that
      endoplasmic reticulum (ER) stress was activated under hormones treatment. To
      identify the cellular mechanism of regulation of endometrial function, we
      investigated the effect of ER stress activator thapsigargin (TG) and inhibitor 4
      phenyl butyric acid (4-PBA) on EECs. We found that TG, which activated the three
      branches of UPR, increased the expression of genes associated with promoting
      conceptus elongation and cellular attachment, significantly up-regulated the
      spheroid attachment rate and PGE2 /PGF2alpha ratio. 4-PBA pre-treatment inhibited
      UPR and inhibited promoting conceptus elongation and cellular attachment related
      genes, but the spheroid attachment rate and PGE2 /PGF2alpha ratio were not
      changed significantly. Moreover, knockdown of ATF6 via shATF6 promoted the
      conceptus elongation related genes, but increased the dissolution of the corpus
      luteum. Besides, blocking ATF6 attenuated autophagy by activating mammalian
      target of rapamycin (mTOR) pathway. Moreover, rapamycin (mTOR inhibitor) pre
      treatment inhibited the expression of promoting conceptus elongation and
      increased PGE2 /PGF2alpha ratio. Taken together, our study indicated that
      physiological level of ER stress may contribute to early pregnancy success, and
      ATF6 signaling pathway cooperated with autophagy to regulate endometrial function
      by modulating mTOR pathway.

PMID- 29206295
TI  - Simultaneous adaptation and maladaptation of tree populations to local
      rhizosphere microbial communities at different taxonomic scales.
AB  - Plant populations are often adapted to their local conditions, but the specific
      selective forces creating this adaptation are often unclear. All plants interact
      with diverse microbial communities, but we know little about how these microbial
      communities as a whole shape the evolutionary trajectory of plant populations. We
      tested whether tree populations were adapted or maladapted to their local
      rhizosphere microbial communities by growing seedlings sourced from multiple
      locations with soil microbial communities from all locations in a fully
      reciprocal design, using seedling growth as a proxy for fitness. In addition, we
      compared the microbial composition of the experimental inocula with that of the
      communities we detected associating with naturally occurring trees at the
      seedling source populations. We found that seedlings grew similarly when
      inoculated with local vs foreign microbial communities, but this neutral response
      derived from conflicting patterns - plant populations appeared to be adapted to
      the presence or absence of whole taxonomic groups in their local microbial
      community, but were simultaneously maladapted to the particular microbial
      populations present in their local site. As rapid climate change and other
      factors push tree populations into new areas, the successful establishment of
      seedlings may depend critically on the balance between the novelty and
      familiarity of the microbial communities they encounter.

PMID- 29206297
TI  - Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers?
AB  - Wnt signaling is an evolutionary highly conserved pathway that is modulated by
      several inhibitors and activators, and plays a key role in numerous physiological
      processes. One of the extracellular Wnt inhibitors is the DKK (Dickkopf Homolog)
      family which has four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1
      (soggy). DKK3 is a divergent member of the DKK protein family. Evidence suggests
      that DKK3 may serve as a potential therapeutic target in several types of human
      cancers. We review here the biological role of DKK3 as a tumor suppressor gene
      (TSG) or oncogene, and its correlation with various miRNAs. In addition, we
      discuss the role of polymorphisms and promoter methylation of the DKK3 gene, and
      of its expression in regulating cancer cell proliferation. Finally, we propose
      that DKK3 may be considered as both a biomarker and a therapeutic target in
      different cancers.

PMID- 29206296
TI  - Comparative plastome genomics and phylogenomics of Brachypodium: flowering time
      signatures, introgression and recombination in recently diverged ecotypes.
AB  - Few pan-genomic studies have been conducted in plants, and none of them have
      focused on the intraspecific diversity and evolution of their plastid genomes. We
      address this issue in Brachypodium distachyon and its close relatives B. stacei
      and B. hybridum, for which a large genomic data set has been compiled. We analyze
      inter- and intraspecific plastid comparative genomics and phylogenomic
      relationships within a family-wide framework. Major indel differences were
      detected between Brachypodium plastomes. Within B. distachyon, we detected two
      main lineages, a mostly Extremely Delayed Flowering (EDF+) clade and a mostly
      Spanish (S+) - Turkish (T+) clade, plus nine chloroplast capture and two plastid
      DNA (ptDNA) introgression and micro-recombination events. Early Oligocene (30.9
      million yr ago (Ma)) and Late Miocene (10.1 Ma) divergence times were inferred
      for the respective stem and crown nodes of Brachypodium and a very recent Mid
      Pleistocene (0.9 Ma) time for the B. distachyon split. Flowering time variation
      is a main factor driving rapid intraspecific divergence in B. distachyon,
      although it is counterbalanced by repeated introgression between previously
      isolated lineages. Swapping of plastomes between the three different genomic
      groups, EDF+, T+, S+, probably resulted from random backcrossing followed by
      stabilization through selection pressure.

PMID- 29206298
TI  - Effects of poly(I:C) and MF59 co-adjuvants on immunogenicity and efficacy of
      survivin polypeptide immunogen against melanoma.
AB  - Malignant tumors pose a public health problem that jeopardizes human life and
      quality of living. At present, tumor vaccines in clinical research typically are
      aimed at stimulating the cellular immune response, while more effective vaccines
      should take into account the synergy between broad spectrum antibodies and high
      levels of cellular immunity. In this study, epitope peptides (68-81, 95-104, 80
      88) of the tumor antigen survivin were chosen as immunogens and supplemented with
      poly(I:C) and/or MF59 adjuvant to evaluate the immune effects and anti-melanoma
      activities. The results indicated that poly(I:C) and MF59 could assist the
      survivin epitope peptide immunogen to control the tumor size, quality, and volume
      in black melanoma mouse models. Analyses by antibody titering, antibody isotyping
      and ELISPOT suggested that the adjuvanted immunogen could induce humoral immunity
      in mice. Poly(I:C) and MF59 combined with survivin peptide 95-104 could
      effectively induce humoral immunity mediated by type 2 T helper (Th2) cells. This
      study provides a basis for candidate immunogen design based on survivin and
      provides support for tumor therapy that can induce a more balanced Th1/Th2 immune
      response.

PMID- 29206299
TI  - microRNA-137 promotes endothelial progenitor cell proliferation and angiogenesis
      in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway.
AB  - Cerebral ischemic stroke (CIS) is one of the common causes of death and
      disability worldwide. This study aims to investigate effect of miR-137 on
      endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the
      Notch pathway. Brain tissues were extracted from CIS and normal mice.
      Immunohistochemistry was used to determine positive rate of NR4A2 expression.
      Serum VEGF, Ang, HGF, and IkappaBalpha levels were determined by ELISA. RT-qPCR
      and Western blotting were used to determine expression of related factors.
      Endothelial progenitor cells in CIS mice were treated and grouped into blank, NC,
      miR-137 mimic, miR-137 inhibitor, siRNA-NR4A2, and miR-137 inhibitor + siRNA
      NR4A2 groups, and cells in normal mice into normal group. Proliferation and
      apoptosis were determined by MTT and flow cytometry, respectively. NR4A2 protein
      expression was strongly positive in CIS mice, which showed higher serum levels of
      VEGF, Ang, and HGF but lower IkappaBalpha than normal mice. Compared with normal
      group, the rest groups (endothelial progenitor cells from CIS mice) showed
      decreased expressions of miR-137, Hes1, Hes5, and IkappaBalpha but elevated
      NR4A2, Notch, Jagged1, Hey-2, VEGF, Ang, and HGF, inhibited proliferation and
      enhanced apoptosis. Compared with blank and NC groups, the miR-137 mimic and
      siRNA-NR4A2 groups exhibited increased expression of miR-137, Hes1, Hes5, and
      IkappaBalpha, but decreased NR4A2, Notch, Jagged1, and Hey-2, with enhanced
      proliferation and attenuated apoptosis. The miR-137 inhibitor group reversed the
      conditions. miR-137 enhances the endothelial progenitor cell proliferation and
      angiogenesis in CIS mice by targeting NR4A2 through the Notch signaling pathway.

PMID- 29206300
TI  - Effects of mTOR/NF-kappaB signaling pathway and high thoracic epidural anesthesia
      on myocardial ischemia-reperfusion injury via autophagy in rats.
AB  - We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B
      (mTOR/NF-kappaB) signaling pathway in high thoracic epidural anesthesia (HTEA)
      against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of
      myocardial I/R injury was established. Ninety rats were divided into the normal,
      sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect
      cardiac function indexes. HE staining was conducted to observe histopathological
      changes of myocardial tissues, and TTC staining was performed to detect the
      myocardial infarction size. TUNEL staining was adopted to detect the cell
      apoptosis rate. The mRNA and protein levels of mTOR, NF-kappaB, Fasl, Bcl-2 and
      Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western
      blotting, respectively. The findings indicated that compared with the normal and
      sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial
      infarction size and increased cell apoptosis rate, while the results in the HTEA
      + PDTC group were opposite. Compared with the normal and sham groups, the I/R
      group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and
      elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA
      + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed
      the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65,
      Bax, and Fasl. These results prove that the inhibition of mTOR/NF-kappaB
      signaling pathway potentiates HTEA against myocardial IR injury by autophagy and
      apoptosis in rats.

PMID- 29206301
TI  - Evaluation of RNA from human trabecular bone and identification of stable
      reference genes.
AB  - The isolation of good quality RNA from tissues is an essential prerequisite for
      gene expression analysis to study pathophysiological processes. This study
      evaluated the RNA isolated from human trabecular bone and defined a set of stable
      reference genes. After pulverization, RNA was extracted with a phenol/chloroform
      method and then purified using silica columns. The A260/280 ratio, A260/230
      ratio, RIN, and ribosomal ratio were measured to evaluate RNA quality and
      integrity. Moreover, the expression of six candidates was analyzed by qPCR and
      different algorithms were applied to assess reference gene stability. A good
      purity and quality of RNA was achieved according to A260/280 and A260/230 ratios,
      and RIN values. TBP, YWHAZ, and PGK1 were the most stable reference genes that
      should be used for gene expression analysis. In summary, the method proposed is
      suitable for gene expression evaluation in human bone and a set of reliable
      reference genes has been identified.

PMID- 29206302
TI  - Network analysis of hippocampal neurons by microelectrode array in the presence
      of HIV-1 Tat and cocaine.
AB  - HIV-associated neurocognitive disorders affecting greater than 30% of patients
      are caused by HIV-1 infection of the CNS, and in part, include neurotoxic effects
      of the viral transactivator of transcription, Tat protein. In addition to
      increasing the risk for becoming HIV infected, cocaine abuse enhances the
      neuropathogenic impacts of HIV-1. To investigate the outcome of Tat and cocaine
      interference in the hippocampal neuronal network, cross-rank-corrlation was
      employed to develop a systematic framework to assess hippocampal neurons behavior
      cultured on multielectrode arrays. Tat and cocaine differentially disturbed
      neuronal spiking rates, amplitude, synchronous activity, and oscillations within
      the hippocampal neuronal network via potentiation of inhibitory
      neurotransmission. The Tat-mediated impairment of neuronal spiking was reversible
      by removal of Tat, which restored neuronal activity. The presence of astrocytes
      co-cultured with neuronal networks diminished the effects of Tat and cocaine on
      neuron function suggesting a role for astrocytes in stabilizing neuronal behavior
      and increasing neuronal spontaneous activities such as bursting amplitude,
      frequency, and wave propagation rate. Taken together, our studies indicate that
      the HIV protein Tat and cocaine impair hippocampal neuronal network functioning
      and that the presence of astrocytes alleviates network dysfunction pointing to a
      newly discovered pathway through which ionic homeostasis is maintained by neuron
      glial crosstalk in the CNS.

PMID- 29206303
TI  - The iron-regulated transporter 1 plays an essential role in uptake, translocation
      and grain-loading of manganese, but not iron, in barley.
AB  - Transporters involved in manganese (Mn) uptake and intracellular Mn homeostasis
      in Arabidopsis and rice are well characterized, while much less is known for
      barley, which is particularly prone to Mn deficiency. In this study we have
      investigated the role of the iron-regulated transporter 1 (IRT1) for Mn uptake
      and translocation in barley plants. We employed an RNAi approach to reduce HvIRT1
      expression to 5% of the wild-type level. This enabled characterization of the
      functional role of HvIRT1 by use of advanced imaging and phenotyping techniques
      applied to plants growing in hydroponics or soils with different Mn availability.
      Our results highlight the importance of HvIRT1 for the transport of Mn across the
      root endodermis into the stele. In the hvirt1-RNAi lines, a chlorotic phenotype
      with reduced shoot Mn concentration and impaired photosynthetic functionality was
      observed, especially under conditions with low Mn availability. We also document
      that HvIRT1 controlled the Mn distribution within the barley grain. Surprisingly,
      unlike other IRT1 orthologues, HvIRT1 played no significant role in iron uptake.
      We conclude that the barley IRT1 orthologue has a novel function with respect to
      ensuring sufficient shoot Mn concentrations. The preference of IRT1 for Mn
      instead of Fe is discussed in an evolutionary context.

PMID- 29206304
TI  - Modulation of Nickel Pyridinedicarboxamidate Complexes to Explore the Properties
      of High-valent Oxidants.
AB  - High-valent Ni oxidants have been implicated in hydrocarbon oxidation catalysis,
      however, little is understood about the properties of these oxidants. Herein, a
      family of NiII complexes supported by a pyridinedicarboxamidate ligand and
      different ancillary ligands was synthesized. The series spans coordination
      numbers 4, 5, and 6, and contains neutral, mono- and di-anionic donor types. X
      ray crystallography and magnetic measurements showed that the 4-coordinate
      complexes were square planar and low spin (S=0) and the 5- and 6-coordinate were
      intermediate spin (S=1). The NiII complexes could be oxidized by one electron to
      form a series of metastable NiIII species. EPR analysis confirmed their
      description as S=1/2 NiIII compounds with signal shape and hyperfine coupling
      dependent on the coordination environment. The oxidation of phenols by the NiIII
      species was probed, providing evidence for a correlation between oxidizing power
      and electron-donating properties of the supporting ligands. Critically, we found
      that the pyridinedicarboxamidate ligand may be a non-innocent proton acceptor in
      the oxidation reactions.

PMID- 29206305
TI  - High-Flux Zeolitic Imidazolate Framework Membranes for Propylene/Propane
      Separation by Postsynthetic Linker Exchange.
AB  - While zeolitic imidazolate framework, ZIF-8, membranes show impressive
      propylene/propane separation, their throughput needs to be greatly improved for
      practical applications. A method is described that drastically reduces the
      effective thickness of ZIF-8 membranes, thereby substantially improving their
      propylene permeance (that is, flux). The new strategy is based on a controlled
      single-crystal to single-crystal linker exchange of 2-methylimidazole in ZIF-8
      membrane grains with 2-imidazolecarboxaldehyde (ZIF-90 linker), thereby enlarging
      the effective aperture size of ZIF-8. The linker-exchanged ZIF-8 membranes showed
      a drastic increase in propylene permeance by about four times, with a negligible
      loss in propylene/propane separation factor when compared to as-prepared
      membranes. The linker-exchange effect depends on the membrane synthesis method.

PMID- 29206306
TI  - Nail-extracting behaviour as an unusual manifestation of adjustment disorder,
      confused with onychotillomania.

PMID- 29206308
TI  - Classification of early-stage non-small cell lung cancer by weighing gene
      expression profiles with connectivity information.
AB  - Pathway-based feature selection algorithms, which utilize biological information
      contained in pathways to guide which features/genes should be selected, have
      evolved quickly and become widespread in the field of bioinformatics. Based on
      how the pathway information is incorporated, we classify pathway-based feature
      selection algorithms into three major categories-penalty, stepwise forward, and
      weighting. Compared to the first two categories, the weighting methods have been
      underutilized even though they are usually the simplest ones. In this article, we
      constructed three different genes' connectivity information-based weights for
      each gene and then conducted feature selection upon the resulting weighted gene
      expression profiles. Using both simulations and a real-world application, we have
      demonstrated that when the data-driven connectivity information constructed from
      the data of specific disease under study is considered, the resulting weighted
      gene expression profiles slightly outperform the original expression profiles. In
      summary, a big challenge faced by the weighting method is how to estimate pathway
      knowledge-based weights more accurately and precisely. Only until the issue is
      conquered successfully will wide utilization of the weighting methods be
      impossible.

PMID- 29206309
TI  - A Direct Proof of the Resonance-Impaired Hydrogen Bond (RIHB) Concept.
AB  - The concept of resonance-enhanced hydrogen bond (RAHB) has been widely accepted
      and applied as it highlights the positive impact of pi-conjugation on
      intramolecular H-bonds. However, electron delocalization is directional and there
      is a possibility that pi-resonance goes from the H-bond acceptor to the H-bond
      donor, leading to a negative impact on H-bonds. Here we used the block-localized
      wavefunction (BLW) method which is a variant of ab initio valence bond (VB)
      theory and able to derive strictly electron-localized structures self
      consistently, to quantify the interplay between H-bond and pi-resonance in the
      terms of geometry, energetics and spectral properties. The comparison of
      geometrical optimizations with and without pi-resonance shows that conjugation
      can indeed either enhance or weaken intramolecular H-bonds. We further
      experimented with various substituents attached to either the H-bond acceptor
      and/or H-bond donor side(s) to tune the H-bonding strength in both directions.

PMID- 29206307
TI  - Osteoprotection Through the Deletion of the Transcription Factor Rorbeta in Mice.
AB  - There is a clinical need to identify new molecular targets for the treatment of
      osteoporosis, particularly those that simultaneously inhibit bone resorption
      while stimulating bone formation. We have previously shown in overexpression
      studies that retinoic acid receptor-related orphan receptor beta (Rorbeta)
      suppresses in vitro osteoblast differentiation. In addition, the expression of
      Rorbeta is markedly increased in bone marrow-derived mesenchymal stromal cells
      with aging in both mice and humans. Here we establish a critical role for Rorbeta
      in regulating bone metabolism using a combination of in vitro and in vivo
      studies. We used Clustered Regularly Interspaced Short Palindromic Repeats
      (CRISPR)/Cas9 gene editing to demonstrate that loss of Rorbeta in osteoblasts
      enhances Wnt signaling, specifically through increased recruitment of beta
      catenin to T-cell factor/lymphoid enhancer factor (Tcf/Lef) DNA binding sites in
      the promoters of the Wnt target genes Tcf7 and Opg. This resulted in increased
      osteogenic gene expression and suppressed osteoclast formation through increased
      osteoprotegerin (OPG) secretion in Rorbeta-deficient cells. Consistent with our
      in vitro data, genetic deletion of Rorbeta in both female and male mice resulted
      in preserved bone mass and microarchitecture with advancing age due to increased
      bone formation with a concomitant decrease in resorption. The improved skeletal
      phenotype in the Rorbeta-/- mice was also associated with increased bone protein
      levels of TCF7 and OPG. These data demonstrate that loss of Rorbeta has
      beneficial skeletal effects by increasing bone formation and decreasing bone
      resorption, at least in part through beta-catenin-dependent activation of the Wnt
      pathway. Thus, inhibition of Rorbeta represents a novel approach to potentially
      prevent or reverse osteoporosis. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 29206310
TI  - Ease of Fill Port Access During the Ultrasound-Guided vs. the Blind Refill
      Technique of Intrathecal Drug Delivery Systems With a Raised Septum, a
      Prospective Comparison Study.
AB  - OBJECTIVES: The localization of the reservoir fill port of Intrathecal Drug
      Delivery Devices (IDDS) can be difficult. The purpose of this study was to assess
      the ease of fill port access during the ultrasound-guided refill technique
      compared to the blind refill technique in IDDSs with a raised septum on the pump
      surface. MATERIALS AND METHODS: Written informed consent was obtained from 19
      adult patients undergoing regular refills of their Raised Septum IDDSs (RS
      IDDSs). The primary outcome of this single center prospective comparison study
      was the number of attempts to enter the reservoir fill port with the needle
      comparing the ultrasound-guided technique vs. the blind technique. The number of
      skin punctures per refill procedure and time to enter the reservoir fill port was
      secondary outcomes. For between group comparisons the Friedman test for repeated
      measures on ranks was used. RESULTS: One hundred and eleven refill procedures
      were assessed in 19 patients over a period of 24 months. The median number of
      attempts to enter the reservoir fill port with the needle differed significantly
      between the ultrasound-guided technique and the blind technique (4 [IQR: 1-6] vs.
      1 [IQR: 1-3], p = 0.018), in favor of the blind technique. The median time to
      enter the reservoir fill port differed significantly between the ultrasound
      guided technique and the blind technique (58 sec [IQR: 38-94] vs. 22 sec [IQR: 16
      40], p < 0.001). CONCLUSIONS: The results of this study suggest that for a RS
      IDDS the blind refill technique needs significantly less attempts to enter the
      reservoir fill port than the US-guided refill technique.

PMID- 29206311
TI  - The Expanding Life and Functions of Osteogenic Cells: From Simple Bone-Making
      Cells to Multifunctional Cells and Beyond.
AB  - During the last three decades, important progress in bone cell biology and in
      human and mouse genetics led to major advances in our understanding of the life
      and functions of cells of the osteoblast lineage. Previously unrecognized sources
      of osteogenic cells have been identified. Novel cellular and molecular mechanisms
      controlling osteoblast differentiation and senescence have been determined. New
      mechanisms of communications between osteogenic cells, osteocytes, osteoclasts,
      and chondrocytes, as well as novel links between osteogenic cells and blood
      vessels have been identified. Additionally, cells of the osteoblast lineage were
      shown to be important components of the hematopoietic niche and to be implicated
      in hematologic dysfunctions and malignancy. Lastly, unexpected interactions were
      found between osteogenic cells and several soft tissues, including the central
      nervous system, gut, muscle, fat, and testis through the release of paracrine
      factors, making osteogenic cells multifunctional regulatory cells, in addition to
      their bone-making function. These discoveries considerably enlarged our vision of
      the life and functions of osteogenic cells, which may lead to the development of
      novel therapeutics with immediate applications in bone disorders. (c) 2017
      American Society for Bone and Mineral Research.

PMID- 29206312
TI  - Risk of cancer in children exposed to antiretroviral nucleoside analogues in
      utero: The french experience.
AB  - All nucleoside analogues for treating HIV infection, due to their capacity to
      integrate into and alter human DNA, are experimentally genotoxic to some extent.
      The long-term oncogenic risk after in utero exposure remains to be determined.
      Cancer incidence in uninfected children exposed to nucleos(t)ide reverse
      transcriptase inhibitors (NRTIs) was evaluated, by cross-checking against the
      National Cancer Registry, in the French perinatal study of children born to HIV+
      mothers. Twenty-one cancers were identified in 15,163 children (median age: 9.9
      years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in
      utero between 1990 and 2014. Five of these children were exposed to zidovudine
      monotherapy, and 15 to various combinations, seven of which included didanosine.
      Overall, the total number of cases was not significantly different from that
      expected for the general population (SIR = 0.8[0.47-1.24]), but the number of
      cases after didanosine exposure was twice that expected (SIR = 2.5 [1.01-5.19]).
      Didanosine accounted for only 10% of prescriptions but was associated with one
      third of cancers. In multivariate analysis, didanosine exposure was significantly
      associated with higher risk (HR = 3.0 [0.9-9.8]). This risk was specifically
      linked to first-trimester exposure (HR = 5.5 [2.1-14.4]). Three cases of
      pineoblastoma, a very rare cancer, were observed, whereas 0.03 were expected. Two
      were associated with didanosine exposure. Despite reassuring data overall, there
      is strong evidence to suggest that didanosine displays transplacental
      oncogenicity. These findings cannot be extrapolated to other NRTIs, but they
      highlight the need for comprehensive evaluations of the transplacental
      genotoxicity of this antiretroviral class. Environ. Mol. Mutagen., 2017. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29206313
TI  - The impact of using peer interviewers in a study of patient empowerment amongst
      people in cancer follow-up.
AB  - BACKGROUND: A range of benefits have been reported from engaging peer
      interviewers in qualitative interviews, but little systematic evaluation exists
      to assess their impact on both process and outcomes of qualitative interviews in
      health research. OBJECTIVE: To investigate the impact of involving patient
      representatives as peer interviewers in a research project on patient
      empowerment. DESIGN: 18 interviews were carried out as part of the wider study,
      seven by the academic researcher alone and eleven jointly with a peer
      interviewer. The interviews were analysed quantitatively and qualitatively to
      explore potential differences between interviews conducted by the researcher
      alone and interviews conducted jointly by the researcher and the peer
      interviewers. A phone evaluation of the peer interviews was carried out with the
      research participants, and notes were thematically analysed to understand their
      experiences. RESULTS: Differences were identified between the academic researcher
      and the peer interviewers in the types of questions they asked and the degree to
      which personal narrative was used in the interview. Peer interviewers varied
      significantly in their approach. Research participants were positive about the
      experience of being interviewed by a peer interviewer. No firm conclusions could
      be made about impact on outcomes. DISCUSSION AND CONCLUSIONS: The uniqueness and
      complexity of qualitative interviews made it difficult to provide any firm
      conclusions about the impact of having peer interviewers on the research
      outcomes, and the benefits identified from the analysis mostly related to the
      process of the interviews. Benefits from using peer interviewers need to be
      considered alongside relevant ethical considerations, and available resources for
      training and support.

PMID- 29206314
TI  - Inhibition of spinal p38 MAPK prevents articular neutrophil infiltration in
      experimental arthritis via sympathetic activation.
AB  - The central nervous system controls the innate immunity by modulating efferent
      neuronal networks. Recently, we have reported that central brain stimulation
      inhibits inflammatory responses. In the present study, we investigate whether
      spinal p38 mitogen-activated protein kinase (MAPK) affects joint inflammation in
      experimental arthritis. Firstly, we observed that intra-articular administration
      of zymosan in mice induces the phosphorylation of the spinal cord p38 MAPK. In
      addition, we demonstrated that spinal p38 MAPK inhibition with intrathecal
      injection of SB203580, a conventional and well-characterized inhibitor, prevents
      knee joint neutrophil recruitment, edema formation, experimental score and
      cytokine production. This local anti-inflammatory effect was completely abolished
      with chemical sympathectomy (guanethidine) and beta-adrenergic receptors blockade
      (nadolol). In conclusion, our results suggest that pharmacological strategies
      involving the modulation of spinal p38 MAPK circuit can prevent joint
      inflammation via sympathetic networks and beta-adrenoceptors activation.

PMID- 29206315
TI  - Intrathecal Trialing of Continuous Infusion Combination Therapy With
      Hydromorphone and Bupivacaine in Failed Back Surgery Patients.
AB  - OBJECTIVES: Intrathecal (IT) trial is a prognostic interventional pain management
      procedure employed to determine the potential success of treating intractable
      pain with an implantable infusion device system. There is a dearth of data
      regarding trials with continuous infusion of combination therapy (e.g. opioid
      combined with local anesthetic). The objective of the this study was to determine
      the overall outcomes of continuous infusion IT trials and factors influencing
      long-term success of IT therapy in patients with chronic intractable pain post
      laminectomy. MATERIALS AND METHODS: This is a retrospective analysis of all
      patients with lumbar failed back surgery syndrome (FBSS) who were trialed with a
      combination of hydromorphone and bupivacaine with a temporary externalized IT
      catheter from March 2007 to June 2014. RESULTS: From a cohort of 62 patients
      fulfilling the inclusion criteria, 54 (87.10%) patients had successful IT trials.
      No significant differences were found between successful and failed trial
      patients with regards to age, sex, pre-trial pain numeric rating scale scores,
      pre-trial morphine equivalent daily dose, or trial dosages. Significant positive
      correlations were found between pretrial oral opioid intake and end of trial
      hydromorphone dose and hydromorphone dose escalation at 12 months and 24 months.
      CONCLUSIONS: Patients with refractory low back pain due to FBSS who underwent
      successful combination IT trial with hydromorphone and bupivacaine infused
      through a temporary IT catheter had significantly improved pain intensity scores
      following permanent implant. Higher pre-trial MEDD was correlated with higher
      trial and post-implant opioid doses and higher rates of opioid dose escalation
      post-implant.

PMID- 29206318
TI  - Automated quality assessment of structural magnetic resonance images in children:
      Comparison with visual inspection and surface-based reconstruction.
AB  - Motion-related artifacts are one of the major challenges associated with
      pediatric neuroimaging. Recent studies have shown a relationship between visual
      quality ratings of T1 images and cortical reconstruction measures. Automated
      algorithms offer more precision in quantifying movement-related artifacts
      compared to visual inspection. Thus, the goal of this study was to test three
      different automated quality assessment algorithms for structural MRI scans. The
      three algorithms included a Fourier-, integral-, and a gradient-based approach
      which were run on raw T1 -weighted imaging data collected from four different
      scanners. The four cohorts included a total of 6,662 MRI scans from two waves of
      the Generation R Study, the NIH NHGRI Study, and the GUSTO Study. Using receiver
      operating characteristics with visually inspected quality ratings of the T1
      images, the area under the curve (AUC) for the gradient algorithm, which
      performed better than either the integral or Fourier approaches, was 0.95, 0.88,
      and 0.82 for the Generation R, NHGRI, and GUSTO studies, respectively. For scans
      of poor initial quality, repeating the scan often resulted in a better quality
      second image. Finally, we found that even minor differences in automated quality
      measurements were associated with FreeSurfer derived measures of cortical
      thickness and surface area, even in scans that were rated as good quality. Our
      findings suggest that the inclusion of automated quality assessment measures can
      augment visual inspection and may find use as a covariate in analyses or to
      identify thresholds to exclude poor quality data.

PMID- 29206319
TI  - Cost-utility Analysis of the National Health Screening Program for Chronic Kidney
      Disease in Korea.
AB  - AIM: Although a national health screening program (NHSP) for chronic kidney
      disease (CKD) has been implemented in Korea since 2002, its cost-effectiveness
      has never been determined. This study aimed to estimate the cost-utility of NHSP
      for CKD in Korea. METHODS: A Markov decision analytic model was constructed to
      compare CKD screening strategies of the NHSP with no screening. We developed a
      model that simulated disease progression in a cohort aged 20 to 120 years or
      death from the societal perspective. RESULTS: Biannual screening starting at age
      40 for CKD by proteinuria (dipstick) and estimated glomerular filtration ratio
      had an ICUR of $66,874/QALY relative to no screening. The targeted screening
      strategy had an ICUR of $37,812/QALY and $40,787/QALY for persons with diabetes
      and hypertension, respectively. ICURs improved with lower cost strategies. The
      most influential parameter that might make screening more cost-effective was the
      effectiveness of treatment on CKD to decrease disease progression and mortality.
      CONCLUSIONS: The Korean NHSP for CKD is more cost-effective for patients with
      diabetes or hypertension than the general population, consistent with prior
      studies. Although it is too early to conclude the cost-effectiveness of the
      Korean NHSP for CKD, this study provides evidence that is useful in evaluating
      the cost-effectiveness of CKD interventions.

PMID- 29206316
TI  - Complementary Strategies for Directed C(sp3 )-H Functionalization: A Comparison
      of Transition-Metal-Catalyzed Activation, Hydrogen Atom Transfer, and
      Carbene/Nitrene Transfer.
AB  - The functionalization of C(sp3 )-H bonds streamlines chemical synthesis by
      allowing the use of simple molecules and providing novel synthetic
      disconnections. Intensive recent efforts in the development of new reactions
      based on C-H functionalization have led to its wider adoption across a range of
      research areas. This Review discusses the strengths and weaknesses of three main
      approaches: transition-metal-catalyzed C-H activation, 1,n-hydrogen atom
      transfer, and transition-metal-catalyzed carbene/nitrene transfer, for the
      directed functionalization of unactivated C(sp3 )-H bonds. For each strategy, the
      scope, the reactivity of different C-H bonds, the position of the reacting C-H
      bonds relative to the directing group, and stereochemical outcomes are
      illustrated with examples in the literature. The aim of this Review is to provide
      guidance for the use of C-H functionalization reactions and inspire future
      research in this area.

PMID- 29206320
TI  - A farnesyl pyrophosphate synthase gene expressed in pollen functions in S-RNase
      independent unilateral incompatibility.
AB  - Multiple independent and overlapping pollen rejection pathways contribute to
      unilateral interspecific incompatibility (UI). In crosses between tomato species,
      pollen rejection usually occurs when the female parent is self-incompatible (SI)
      and the male parent self-compatible (SC) (the 'SI * SC rule'). Additional, as yet
      unknown, UI mechanisms are independent of self-incompatibility and contribute to
      UI between SC species or populations. We identified a major quantitative trait
      locus on chromosome 10 (ui10.1) which affects pollen-side UI responses in crosses
      between cultivated tomato, Solanum lycopersicum, and Solanum pennelliiLA0716,
      both of which are SC and lack S-RNase, the pistil determinant of S-specificity in
      Solanaceae. Here we show that ui10.1 is a farnesyl pyrophosphate synthase gene
      (FPS2) expressed in pollen. Expression is about 18-fold higher in pollen of S.
      pennellii than in S. lycopersicum. Pollen with the hypomorphic S. lycopersicum
      allele is selectively eliminated on pistils of the F1 hybrid, leading to
      transmission ratio distortion in the F2 progeny. CRISPR/Cas9-generated knockout
      mutants (fps2) in S. pennelliiLA0716 are self-sterile due to pollen rejection,
      but mutant pollen is fully functional on pistils of S. lycopersicum. F2 progeny
      of S. lycopersicum * S. pennellii (fps2) show reversed transmission ratio
      distortion due to selective elimination of pollen bearing the knockout allele.
      Overexpression of FPS2 in S. lycopersicum pollen rescues the pollen elimination
      phenotype. FPS2-based pollen selectivity does not involve S-RNase and has not
      been previously linked to UI. Our results point to an entirely new mechanism of
      interspecific pollen rejection in plants.

PMID- 29206321
TI  - Factors affecting operative time in robotic thyroidectomy.
AB  - BACKGROUND: The purpose of this study was to evaluate factors related to
      operative time in robotic thyroidectomy. METHODS: We retrospectively analyzed 240
      patients who underwent robotic thyroidectomy. The total thyroidectomy cases and
      lobectomy cases were both categorized into those with long operative times (LOTs;
      upper 25% of cases) and those with short operative times (SOTs; lower 25%).
      RESULTS: Among the total thyroidectomy cases, body mass index (BMI) >=23 kg/m2
      (hazard ratio [HR] 5.34; P = .008) and bilateral central neck dissection (CND; HR
      14.92; P = .028) were more frequent in the LOT group in multivariate analysis.
      Among the lobectomy cases, BMI >=23 kg/m2 (HR 12.92; P = .003) and unilateral CND
      (HR 21.38; P = .017) were the only independent risk factors for prolonged
      operative time. CONCLUSION: Body habitus and clinical nodal status in the central
      compartment should be considered in deciding the indications for robotic
      thyroidectomy.

PMID- 29206323
TI  - Impact of intratumoral heterogeneity of breast cancer tissue on quantitative
      metabolomics using high-resolution magic angle spinning 1 H NMR spectroscopy.
AB  - High-resolution magic angle spinning (HR MAS) nuclear magnetic resonance (NMR)
      spectroscopy is increasingly being used to study metabolite levels in human
      breast cancer tissue, assessing, for instance, correlations with prognostic
      factors, survival outcome or therapeutic response. However, the impact of
      intratumoral heterogeneity on metabolite levels in breast tumor tissue has not
      been studied comprehensively. More specifically, when biopsy material is
      analyzed, it remains questionable whether one biopsy is representative of the
      entire tumor. Therefore, multi-core sampling (n = 6) of tumor tissue from three
      patients with breast cancer, followed by lipid (0.9- and 1.3-ppm signals) and
      metabolite quantification using HR MAS 1 H NMR, was performed, resulting in the
      quantification of 32 metabolites. The mean relative standard deviation across all
      metabolites for the six tumor cores sampled from each of the three tumors ranged
      from 0.48 to 0.74. This was considerably higher when compared with a
      morphologically more homogeneous tissue type, here represented by murine liver
      (0.16-0.20). Despite the seemingly high variability observed within the tumor
      tissue, a random forest classifier trained on the original sample set (training
      set) was, with one exception, able to correctly predict the tumor identity of an
      independent series of cores (test set) that were additionally sampled from the
      same three tumors and analyzed blindly. Moreover, significant differences between
      the tumors were identified using one-way analysis of variance (ANOVA), indicating
      that the intertumoral differences for many metabolites were larger than the
      intratumoral differences for these three tumors. That intertumoral differences,
      on average, were larger than intratumoral differences was further supported by
      the analysis of duplicate tissue cores from 15 additional breast tumors. In
      summary, despite the observed intratumoral variability, the results of the
      present study suggest that the analysis of one, or a few, replicates per tumor
      may be acceptable, and supports the feasibility of performing reliable analyses
      of patient tissue.

PMID- 29206322
TI  - 4D flow MRI, cardiac function, and T1 -mapping: Association of valve-mediated
      changes in aortic hemodynamics with left ventricular remodeling.
AB  - BACKGROUND: Patients with bicuspid aortic valve (BAV) show altered hemodynamics
      in the ascending aorta that can be assessed by 4D flow MRI. PURPOSE:
      Comprehensive cardiac MRI was applied to test the hypothesis that BAV-mediated
      changes in aortic hemodynamics (wall shear stress [WSS] and velocity) are
      associated with parameters of left ventricular (LV) remodeling. STUDY TYPE:
      Retrospective data analysis. POPULATION: Forty-nine BAV patients (mean age = 50.2
      +/- 13.5, 62% male). FIELD STRENGTH/SEQUENCE: Balanced steady-state free
      precession (bSSFP)-CINE, pre- and postcontrast T1 mapping with modified Look
      Locker inversion recovery (MOLLI), time-resolved 3D phase-contrast (PC) MRI with
      three-directional velocity encoding (4D flow MRI) at 1.5 and 3T. ASSESSMENT:
      Quantification of LV volumetric data and myocardial mass, extracellular volume
      fraction (ECV), aortic valve stenosis (AS), and regurgitation (AR). 3D aortic
      segmentation, quantification of peak systolic velocities, and 3D WSS in the
      ascending aorta (AAo), arch, and descending aorta (DAo). STATISTICAL TESTS: Two
      sided nonpaired t-test to compare subgroups. Pearson correlation coefficient for
      correlations between aortic hemodynamics and LV parameters. RESULTS: Of the 49
      BAV patients, 35 had aortic valve dysfunction (AS [n = 7], AR [n = 16], both AS
      and AR [n = 12]). Mean systolic WSS in the AAo, peak systolic velocities in the
      AAo and arch, and LV mass were significantly higher (P < 0.001) in the AS/AR
      group compared to the patients without AS/AR. In the complete group, we observed
      significant relationships between increased LV mass and elevated peak systolic
      velocity (r = 0.57, r = 0.58; P < 0.001) and WSS in the AAo and arch,
      respectively (r = 0.54, r = 0.46; P < 0.001). We detected an association between
      ECV and WSS in the AAo (r = 0.38, P = 0.02). These relations did not hold true
      for patients without AV dysfunction. DATA CONCLUSION: AS and AR in BAV patients
      have a major impact on elevated aortic peak velocities and WSS that were
      associated with parameters of LV remodeling. LEVEL OF EVIDENCE: 3 Technical
      Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

PMID- 29206324
TI  - AHNS Series: Do you know your guidelines? Evidence-based management of oral
      cavity cancers.
AB  - Oral cavity squamous cell carcinoma (OCSCC) is the most common nonmelanoma head
      and neck cancer in the world, with an estimated 405 000 new cases expected each
      year. Subsites of the oral cavity include the alveolar ridge, buccal mucosa,
      anterior tongue, tonsillar pillar, retromolar trigone, hard palate, gingiva, and
      floor of the mouth. In this issue of the AHNS "Do you know your guidelines?"
      series, we review the evidence-based approach to the management of oral cavity
      carcinomas based on the framework provided by the National Comprehensive Cancer
      Network (NCCN) Clinical Practice Guidelines in Oncology.

PMID- 29206326
TI  - Assessing the influence of isoflurane anesthesia on cardiac metabolism using
      hyperpolarized [1-13 C]pyruvate.
AB  - Isoflurane is a frequently used anesthetic in small-animal dissolution dynamic
      nuclear polarization-magnetic resonance imaging (DNP-MRI) studies. Although the
      literature suggests interactions with mitochondrial metabolism, the influence of
      the compound on cardiac metabolism has not been assessed systematically to date.
      In the present study, the impact of low versus high isoflurane concentration was
      examined in a crossover experiment in healthy rats. The results revealed that
      cardiac metabolism is modulated by isoflurane concentration, showing increased [1
      13 C]lactate and reduced [13 C]bicarbonate production during high isoflurane
      relative to low isoflurane dose [average differences: +16% [1-13 C]lactate/total
      myocardial carbon, -22% [13 C]bicarbonate/total myocardial carbon; +51% [1-13
      C]lactate/[13 C]bicarbonate]. These findings emphasize that reproducible
      anesthesia is important when studying cardiac metabolism. As the depth of
      anesthesia is difficult to control in an experimental animal setting, careful
      study design is required to exclude confounding factors.

PMID- 29206327
TI  - Pharyngeal perforation after anterior cervical spine surgery treated by transoral
      endoscopic surgery.
AB  - BACKGROUND: Anterior cervical fixation has been used since 1967 for multiple
      pathologies like traumatism, compressive myelopathy, or spinal infections.
      METHODS: We report the case of a patient who had undergone cervical spine surgery
      10 years previously and presented to our clinic with a pharyngeal fistula due to
      surgical screw displacement that was treated by transoral endoscopic surgery.
      RESULTS: The immediate postoperative period occurred without incidence and
      complete odynophagia resolution. The patient was discharged home the fourth day
      after surgery. Follow-up after 1 year showed no evidence of spinal fixation
      hardware mobilization. CONCLUSION: We consider the transoral endoscopic approach
      a feasible low comorbidity technique to treat anterior cervical plate
      mobilization with pharyngeal and pharyngoesophageal perforations.

PMID- 29206328
TI  - Nutritional and hematologic markers as predictors of risk of surgical site
      infection in patients with head and neck cancer undergoing major oncologic
      surgery.
AB  - BACKGROUND: Surgical site infection is a complication of surgery for patients
      with head and neck cancer. We examined the risk factors for surgical site
      infection in patients undergoing surgery for head and neck cancer. METHODS: The
      study involved 369 patients who underwent surgery for head and neck cancer.
      Hematological and nutritional parameters were measured preoperatively and
      postoperatively. Univariate and multivariate analyses were used to determine the
      risk factors for surgical site infection. RESULTS: Of the 369 patients, 104
      (28.2%) had surgical site infections: 45 (12.2%) superficial incisional; 6 (1.6%)
      deep incisional; and 53 (14.4%) organ/space infections. Multivariate analyses
      showed that history of radiotherapy, weight loss at diagnosis (>5%), preoperative
      hypoalbuminemia, neutrophil/lymphocyte ratio (NLR), reconstructive surgery, and
      tracheostomy were the independent factors predictive of surgical site infection.
      Patients with preoperative low serum albumin levels (<3.3 g/L) had a 3-fold
      higher risk of surgical site infection. CONCLUSION: Our study shows that patient
      nutritional and hematological markers are associated with the risk of surgical
      site infection after major surgery for head and neck cancer.

PMID- 29206325
TI  - Growing incidence of thyroid carcinoma in recent years: Factors underlying
      overdiagnosis.
AB  - There is an increasing incidence of well-differentiated thyroid cancer worldwide.
      Much of the increase is secondary to increased detection of small, low-risk
      tumors, with questionable clinical significance. This review addresses the
      factors that contribute to the increasing incidence and considers environmental,
      and patient-based and clinician-led influences. Articles addressing the causes of
      the increased incidence were critically reviewed. A complex interplay of
      environmental, medical, and social pressures has resulted in increased awareness
      of the thyroid disease risk, increased screening of thyroid cancers, and
      increased diagnosis of thyroid cancers. Although there is evidence to suggest
      that the true disease incidence may be changing slightly, most of the increase is
      related to factors that promote early diagnosis of low-risk lesions, which is
      resulting in a significant phenomenon of overdiagnosis. An improved understanding
      of these pressures at a global level will enable healthcare policymakers to react
      appropriately to this challenge in the future.

PMID- 29206329
TI  - Cardiac tissue regeneration: A preliminary study on carbon-based nanotubes
      gelatin scaffold.
AB  - The aim of this study was set-up and test of gelatin and carbon nanotubes
      scaffolds. Gelatin-based (5%) genipin cross-linked (0.2%) scaffolds embedding
      single-walled carbon nanotubes (SWCNTs, 0.3, 0.5, 0.7, 0.9, and 1.3% w/w) were
      prepared and mechanically/electrically characterized. For biological evaluation,
      H9c2 cell line was cultured for 10 days. Cytotoxicity, cell growth and
      differentiation, immunohistochemistry, and real-time PCR analysis were performed.
      Myoblast and cardiac differentiation were obtained by serum reduction to 1% (C1%
      ) and stimulation with 50 nM all trans-retinoic acid (CRA ), respectively.
      Immunohistochemistry showed elongated myotubes in C1% while round and
      multinucleated cells in CRA with also a significantly increased expression of
      natriuretic peptides (NP) and ET-1 receptors in parallel with a decreased ET-1.
      On scaffolds, cell viability was similar for Gel-SWCNT0.3%/0.9% ; NP and ET
      systems expression decreased in both concentrations with respect to control and
      CX-43, mainly due to a lacking of complete differentiation in cardiac phenotype
      during that time. Although further analyses on novel biomaterials are necessary,
      these results represent a useful starting point to develop new biomaterial-based
      scaffolds. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 2750-2762, 2018.

PMID- 29206330
TI  - Differential patterns of dynamic functional connectivity variability of striato
      cortical circuitry in children with benign epilepsy with centrotemporal spikes.
AB  - Benign epilepsy with centrotemporal spikes (BECTS) is characterized by abnormal
      (static) functional interactions among cortical and subcortical regions,
      regardless of the active or chronic epileptic state. However, human brain
      connectivity is dynamic and associated with ongoing rhythmic activity. The
      dynamic functional connectivity (dFC) of the distinct striato-cortical circuitry
      associated with or without interictal epileptiform discharges (IEDs) are poorly
      understood in BECTS. Herein, we captured the pattern of dFC using sliding window
      correlation of putamen subregions in the BECTS (without IEDs, n = 23; with IEDs,
      n = 20) and sex- and age-matched healthy controls (HCs, n = 28) during rest.
      Furthermore, we quantified dFC variability using their standard deviation.
      Compared with HCs and patients without IEDs, patients with IEDs exhibited
      excessive variability in the dorsal striatal-sensorimotor circuitry related to
      typical seizure semiology. By contrast, excessive stability (decreased dFC
      variability) was found in the ventral striatal-cognitive circuitry (p < .05, GRF
      corrected). In addition, correlation analysis revealed that the excessive
      variability in the dorsal striatal-sensorimotor circuitry was related to highly
      frequent IEDs (p < .05, uncorrected). Our finding of excessive variability in the
      dorsal striatal-sensorimotor circuitry could be an indication of increased
      sensitivity to regional fluctuations in the epileptogenic zone, while excessive
      stability in the ventral striatal-cognitive circuitry could represent
      compensatory mechanisms that prevent or postpone cognitive impairments in BECTS.
      Overall, the differentiated dynamics of the striato-cortical circuitry extend our
      understanding of interactions among epileptic activity, striato-cortical
      functional architecture, and neurocognitive processes in BECTS.

PMID- 29206331
TI  - Bacterial nanocellulose-IKVAV hydrogel matrix modulates melanoma tumor cell
      adhesion and proliferation and induces vasculogenic mimicry in vitro.
AB  - Vasculogenic mimicry process has generated great interest over the past decade.
      So far, however, there have been only a few matrices available that allow us to
      study that process in vitro. Here, we have developed an innovative hydrogel
      platform with defined composition that mimics the structural architecture and
      biological functions of the extracellular matrix for vasculogenic mimicry of
      human melanoma cells (SK-MEL-28). We chemically immobilized IKVAV peptide on
      bacterial nanocellulose (BNC) fibers. BNC-IKVAV hydrogel was found to improve the
      adhesion and proliferation of SK-MEL-28 cells on the top and bottom surfaces.
      Particularly, the bottom surface of BNC-IKVAV induced SK-MEL-28 cells to organize
      themselves as well-established networks related to the vasculogenic mimicry
      process. Finally, our results showed that not only BNC-IKVAV but also BNC
      hydrogels can potentially be used as a three-dimensional platform that allows the
      screening of antitumor drugs. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 106B: 2741-2749, 2018.

PMID- 29206332
TI  - Inactivation of mTORC1 Signaling in Osterix-Expressing Cells Impairs B-cell
      Differentiation.
AB  - Osteoblasts provide a microenvironmental niche for B-cell commitment and
      maturation in the bone marrow (BM). Any abnormity of osteoblasts function may
      result in the defect of B lymphopoiesis. Signaling from mechanistic target of
      rapamycin complex 1 (mTORC1) has been implicated in regulating the expansion and
      differentiation of osteoblasts. Thus, we raise a hypothesis that mTORC1 signaling
      in osteoblasts plays a vital role in B-cell development. Inactivation of mTORC1
      in osterix-expressing cells (mainly osteoblast lineage) through Osx-Cre-directed
      deletion of Raptor (an mTORC1-specific component) resulted in a reduction in the
      total B-cell population in the BM, which was due to a block in early B-cell
      development from the pro-B to pre-B cell stage. Further mechanistic studies
      revealed that this defect was the result of reduction of interleukin-7 (IL-7)
      expression in osterix-expressing immature osteoblasts, which caused the
      abnormality of IL-7/Stat5 signaling in early B lymphocytes, leading to an
      increased apoptosis of pre-B plus immature B cells. In vitro and in vivo studies
      demonstrated that the addition of exogenous IL-7 partially restored B
      lymphopoiesis in the BM of Raptor mutant mice. Furthermore, total BM cells
      cultured in conditioned media from Raptor null immature osteoblasts or media with
      anti-IL-7 neutralizing antibody failed to differentiate into pre-B and immature B
      cells, indicating that inactivation of mTORC1 in immature osteoblast cannot fully
      support normal B-cell development. Taken together, these findings demonstrate a
      novel role for mTORC1 in the regulation of bone marrow environments that support
      B-cell differentiation via regulating IL-7 expression. (c) 2017 American Society
      for Bone and Mineral Research.

PMID- 29206333
TI  - A Chemical View on X-ray Photoelectron Spectroscopy: the ESCA Molecule and
      Surface-to-Bulk XPS Shifts.
AB  - In this paper we remind the reader of a simple, intuitive picture of chemical
      shifts in X-ray photoelectron spectroscopy (XPS) as the difference in chemical
      bonding between the probed atom and its neighbor to the right in the periodic
      table, the so called Z+1 approximation. We use the classical ESCA molecule, ethyl
      trifluoroacetate, and 4d-transition metals to explicitly demonstrate agreement
      between core-level shifts computed as differences between final core-hole states
      and the approach where each core-ionized atom is replaced by a Z+1 atom. In this
      final state, or total energy picture, the XPS shift arises due to the more or
      less unfavorable chemical bonding of the effective nitrogen in the carbon
      geometry for the ESCA molecule. Surface core level shifts in metals are
      determined by whether the Z+1 atom as an alloy segregates to the surface or is
      more soluble in the bulk. As further illustration of this more chemical picture,
      we compare the geometry of C 1s and O 1s core-ionized CO with that of,
      respectively, NO+ and CF+ . The scope is not to propose a new method to compute
      XPS shifts but rather to stress the validity of this simple interpretation.

PMID- 29206334
TI  - Non-diabetic renal disease in patients with type 2 diabetes: a single centre
      study.
AB  - BACKGROUND: Non-diabetic renal disease (NDRD) has been widely known in diabetic
      patients. The clinical differentiation between diabetic nephropathy (DN) and NDRD
      is still not so clear and effective. AIM: To analyse the pathological
      characteristics and distribution of renal injury in selected type 2 diabetic
      patients. Comparison between DN and NDRD in clinical characteristics, to find
      important predictors for NDRD. METHODS: To conduct retrospective analysis of
      clinical, laboratory and pathohistological data of type 2 diabetic patients in
      whom renal biopsies were performed from March 2010 to September 2014 in Shandong
      Provincial Hospital affiliated to Shandong University (n = 88). RESULTS:
      According to the findings of renal biopsy, the incidences of DN, NDRD and DN
      complicated with NDRD were 20.46, 72.73 and 6.82% respectively. The most common
      NDRD found were: membranous nephropathy, followed by IgA nephropathy and focal
      segmental glomerulosclerosis. In multivariate logistic-analysis, fasting blood
      glucose (odds ratio (OR) 0.714; 95% confidence interval (CI) = 0.543-0.939; P =
      0.016) and absence of diabetic retinopathy (OR 18.602; 95% CI = 2.176-159.018; P
      = 0.003) were independent predictors of NDRD. CONCLUSIONS: This study confirmed a
      considerably high prevalence of NDRD in type 2 diabetic patients with renal
      injury. As some cases of NDRD are readily treatable or remittable, we should
      consider renal biopsy in selected diabetic patients with renal involvement,
      especially in those with effective blood glucose control and the absence of
      diabetic retinopathy.

PMID- 29206335
TI  - Conversion of Olefins into Ketones by an Iron-Catalyzed Wacker-type Oxidation
      Using Oxygen as the Sole Oxidant.
AB  - We describe a mild and operationally simple procedure for the oxidation of
      olefins into ketones. The reaction is catalyzed by the hexadecafluorinated iron
      phthalocyanine complex FePcF16 with stoichiometric amounts of triethylsilane as
      an additive under oxygen atmosphere to give ketones in good to high yields with
      excellent chemoselectivity and functional group tolerance. Ketone formation
      proceeds in up to 95 % yield and with 100 % regioselectivity while the
      corresponding alcohols were observed as side products.

PMID- 29206336
TI  - Claims-based studies of oral glucose-lowering medications can achieve balance in
      critical clinical variables only observed in electronic health records.
AB  - AIM: To evaluate the extent to which balance in unmeasured characteristics of
      patients with type 2 diabetes (T2DM) was achieved in claims data, by comparing
      against more detailed information from linked electronic health records (EHR)
      data. METHODS: Within a large US commercial insurance database and using a cohort
      design, we identified patients with T2DM initiating linagliptin or a comparator
      agent within class (ie, another dipeptidyl peptidase-4 inhibitor) or outside
      class (ie, pioglitazone or a sulphonylurea) between May 2011 and December 2012.
      We focused on comparators used at a similar stage of diabetes to linagliptin. For
      each comparison, 1:1 propensity score (PS) matching was used to balance >100
      baseline claims-based characteristics, including proxies of diabetes severity and
      duration. Additional clinical data from EHR were available for a subset of
      patients. We assessed representativeness of the claims-EHR-linked subset,
      evaluated the balance of claims- and EHR-based covariates before and after PS
      matching via standardized differences (SDs), and quantified the potential bias
      associated with observed imbalances. RESULTS: From a claims-based study
      population of 166 613 patients with T2DM, 7219 (4.3%) patients were linked to
      their EHR data. Claims-based characteristics in the EHR-linked and EHR-unlinked
      patients were similar (SD < 0.1), confirming the representativeness of the EHR
      linked subset. The balance of claims-based and EHR-based patient characteristics
      appeared to be reasonable before PS-matching and generally improved in the PS
      matched population, to be SD < 0.1 for most patient characteristics and SD < 0.2
      for select laboratory results and body mass index categories, which was not large
      enough to cause meaningful confounding. CONCLUSION: In the context of
      pharmacoepidemiological research on diabetes therapy, choosing appropriate
      comparison groups paired with a new-user design and 1:1 PS matching on many
      proxies of diabetes severity and duration improves balance in covariates
      typically unmeasured in administrative claims datasets, to the extent that
      residual confounding is unlikely.

PMID- 29206337
TI  - Organocatalytic Enantioselective Higher-Order Cycloadditions of In Situ Generated
      Amino Isobenzofulvenes.
AB  - The [8+2] cycloaddition of indene-2-carbaldehydes and nitro olefins is described
      to provide benzonorbornene scaffolds in a highly peri-, diastereo-, and
      enantioselective fashion in the presence of a C2 -symmetric aminocatalyst. This
      reaction, which proceeds through a transient semi-aromatic amino isobenzofulvene,
      represents the first example of catalytic formation and transformation of these
      species. Quantum chemical calculations suggest a kinetically controlled stepwise
      mechanism where the stereochemistry is determined in the first bond-forming
      event. Beyond the useful [8+2] cycloadducts, [10+4] cycloadducts have been
      identified in silico as potential off-pathway intermediates.

PMID- 29206338
TI  - Alphanumerical Visual Display Made of DNA Logic Gates for Drug Susceptibility
      Testing of Pathogens.
AB  - Molecular diagnostics of drug-resistant pathogens require the analysis of point
      mutations in bacterial or viral genomes, which is usually performed by trained
      professionals and/or by sophisticated computer algorithms. We have developed a
      DNA-based logic system that autonomously analyzes mutations found in the genome
      of Mycobacterium tuberculosis complex (MTC) bacteria and communicates the output
      to a human user as alphanumeric characters read by the naked eye. The five-gate
      system displays "O" ("no infection") for the absence of MTC infection and "P" or
      "F" for passing or failing a drug-susceptibility test, respectively.

PMID- 29206340
TI  - A Permselective CeOx Coating To Improve the Stability of Oxygen Evolution
      Electrocatalysts.
AB  - Highly active NiFeOx electrocatalysts for the oxygen evolution reaction (OER)
      suffer gradual deactivation with time owing to the loss of Fe species from the
      active sites into solution during catalysis. The anodic deposition of a CeOx
      layer prevents the loss of such Fe species from the OER catalysts, achieving a
      highly stable performance. The CeOx layer does not affect the OER activity of the
      catalyst underneath but exhibits unique permselectivity, allowing the permeation
      of OH- and O2 through while preventing the diffusion of redox ions through the
      layer to function as a selective O2 -evolving electrode. The use of such a
      permselective protective layer provides a new strategy for improving the
      durability of electrocatalysts.

PMID- 29206339
TI  - Reversibility of myocardial metabolism and remodelling in morbidly obese patients
      6 months after bariatric surgery.
AB  - AIMS: To study myocardial substrate uptake, structure and function, before and
      after bariatric surgery, to clarify the interaction between myocardial metabolism
      and cardiac remodelling in morbid obesity. METHODS: We studied 46 obese patients
      (age 44 +/- 10 years, body mass index [BMI] 42 +/- 4 kg/m2 ), including 18 with
      type 2 diabetes (T2D) before and 6 months after bariatric surgery and 25 healthy
      age-matched control group subjects. Myocardial fasting free fatty acid uptake
      (MFAU) and insulin-stimulated myocardial glucose uptake (MGU) were measured using
      positron-emission tomography. Myocardial structure and function, and myocardial
      triglyceride content (MTGC) and intrathoracic fat were measured using magnetic
      resonance imaging and magnetic resonance spectroscopy. RESULTS: The morbidly
      obese study participants, with or without T2D, had cardiac hypertrophy, impaired
      myocardial function and substrate metabolism compared with the control group.
      Surgery led to marked weight reduction and remission of T2D in most of the
      participants. Postoperatively, myocardial function and structure improved and
      myocardial substrate metabolism normalized. Intrathoracic fat, but not MTGC, was
      reduced. Before surgery, BMI and MFAU correlated with left ventricular
      hypertrophy, and BMI, age and intrathoracic fat mass were the main variables
      associated with cardiac function. The improvement in whole-body insulin
      sensitivity correlated positively with the increase in MGU and the decrease in
      MFAU. CONCLUSIONS: In the present study, obesity and age, rather than myocardial
      substrate uptake, were the causes of cardiac remodelling in morbidly obese
      patients with or without T2D. Cardiac remodelling and impaired myocardial
      substrate metabolism are reversible after surgically induced weight loss and
      amelioration of T2D.

PMID- 29206341
TI  - Diversity-Oriented Synthesis of Furo[3,2-c]coumarins and Benzofuranyl Chromenones
      through Chemoselective Acylation/Wittig Reaction.
AB  - A highly efficient and chemoselective one-pot protocol for the diversity-oriented
      synthesis of two types of coumarin-based formal cross-coupling adducts, furo[3,2
      c]coumarins and 3-benzofuranyl chromenones, is described. Key attributes of the
      methodology are an initial chemoselective acylation of functionalized phosphorus
      zwitterions and a subsequent chemoselective intramolecular Wittig reaction that
      preferentially resulted in one of the two coumarin derivatives in high yield,
      depending on relative reactivities and the addition sequence of the acylating
      agents.

PMID- 29206342
TI  - Solventless and Metal-Free Synthesis of High-Molecular-Mass Polyaminoboranes from
      Diisopropylaminoborane and Primary Amines.
AB  - The solventless reaction of diisopropylaminoborane with n-butylamine, at room
      temperature, leads to a mixture of B(sp2) H-, B(sp3) H2 -, and B(sp3) H3 
      containing species. At low temperature, the reaction outcome is completely
      modified, thus leading selectively to the formation of high-mass
      polybutylaminoborane. When extended to a variety of primary amines, under
      solventless conditions and at low temperature, this reaction provides a new,
      efficient, and direct metal-free access to high-molecular-mass polyaminoboranes
      in good to high yields under mild reaction conditions.

PMID- 29206343
TI  - Selective Oxidative [4+2] Imine/Alkene Annulation with H2 Liberation Induced by
      Photo-Oxidation.
AB  - The oxidative [4+2] annulation reaction represents an elegant and versatile
      synthetic protocol for the construction of six-membered heterocyclic compounds.
      Herein, a photoinduced oxidative [4+2] annulation of NH imines and alkenes was
      developed by utilizing a dual photoredox/cobaloxime catalytic system. Various
      multisubstituted 3,4-dihydroisoquinolines can be obtained in good yields. This
      method is not only obviated the need of stiochiometric amounts of oxidants but
      also exhibited excellent atom economy by generating H2 as the only byproduct.
      Remarkably, high regioselectivity and trans diastereoselectivity can be achieved
      in this transformation even if the Z/E mixture of alkenes were employed.

PMID- 29206344
TI  - Balancing selection maintains cryptic colour morphs.
AB  - Animals display incredibly diverse colour patterns, a testament to evolution's
      endless innovation in shaping life. In many species, the interplay between males
      and females in the pursuit of mates has driven the evolution of a myriad of
      colour forms, from the flashy peacock tail feathers to the tiniest colour
      markings in damselflies. In others, colour provides crypsis by allowing to blend
      into the background and to escape the eyes of predators. While the obvious
      benefits of this dazzling diversity for reproduction and survival seem
      straightforward, its maintenance is not. Theory predicts that genetic drift and
      various forms of selection reduce variation over time, making the persistence of
      colour variants over generations a puzzle. In this issue of Molecular Ecology,
      Lindtke et al. () study the cryptic colour morphs of Timema cristinae walking
      sticks to shed light on the genetic architecture and mechanisms that allow colour
      polymorphism maintenance over long timescales. By combining genome-wide data with
      phenotyping information from natural populations, they were able to map the green
      and melanistic colour to one genomic region with highly reduced effective
      recombination rate between two main chromosomal variants, consistent with an
      inversion polymorphism. These two main chromosomal variants showed geographically
      widespread heterozygote excess, and genomic signatures consistent with long-term
      balancing selection. A younger chromosomal variant was detected for the third
      morph, the green-striped colour morphs, in the same genomic regions as the
      melanistic and the green-unstriped morphs. Together, these results suggest that
      the genetic architecture of cryptic T. cristinae morphs is caused by
      nonrecombining genomic blocks that have been maintained over extended time
      periods by balancing selection making this study one of the few available
      empirical examples documenting that balancing selection of various forms may play
      an important role in maintaining adaptive genetic variation in nature.

PMID- 29206345
TI  - Synthesis and Evaluation of N-Phenylpyrrolamides as DNA Gyrase B Inhibitors.
AB  - ATP-competitive inhibitors of DNA gyrase and topoisomerase IV are among the most
      interesting classes of antibacterial drugs that are unrepresented in the
      antibacterial pipeline. We developed 32 new N-phenylpyrrolamides and evaluated
      them against DNA gyrase and topoisomerase IV from E. coli and Staphylococcus
      aureus. Antibacterial activities were studied against Gram-positive and Gram
      negative bacterial strains. The most potent compound displayed an IC50 of 47 nm
      against E. coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12.5
      MUm against the Gram-positive Enterococcus faecalis. Some compounds displayed
      good antibacterial activities against an efflux-pump-deficient E. coli strain
      (MIC=6.25 MUm) and against wild-type E. coli in the presence of efflux pump
      inhibitor PAbetaN (MIC=3.13 MUm). Here we describe new findings regarding the
      structure-activity relationships of N-phenylpyrrolamide DNA gyrase B inhibitors
      and investigate the factors that are important for the antibacterial activity of
      this class of compounds.

PMID- 29206346
TI  - Novel approaches to antifungal therapy.

PMID- 29206347
TI  - Challenges of the economic and social effects of diabetes in low- and middle
      income countries.

PMID- 29206348
TI  - Perfusion-based fluorescence imaging method delineates diverse organs and
      identifies multifocal tumors using generic near-infrared molecular probes.
AB  - Rapid detection of multifocal cancer without the use of complex imaging schemes
      will improve treatment outcomes. In this study, dynamic fluorescence imaging was
      used to harness differences in the perfusion kinetics of near-infrared (NIR)
      fluorescent dyes to visualize structural characteristics of different tissues.
      Using the hydrophobic nontumor-selective NIR dye cypate, and the hydrophilic dye
      LS288, a high tumor-to-background contrast was achieved, allowing the delineation
      of diverse tissue types while maintaining short imaging times. By clustering
      tissue types with similar perfusion properties, the dynamic fluorescence imaging
      method identified secondary tumor locations when only the primary tumor position
      was known, with a respective sensitivity and specificity of 0.97 and 0.75 for
      cypate, and 0.85 and 0.81 for LS288. Histological analysis suggests that the
      vasculature in the connective tissue that directly surrounds the tumor was a
      major factor for tumor identification through perfusion imaging. Although the
      hydrophobic dye showed higher specificity than the hydrophilic probe, use of
      other dyes with different physical and biological properties could further
      improve the accuracy of the dynamic imaging platform to identify multifocal
      tumors for potential use in real-time intraoperative procedures.

PMID- 29206349
TI  - Mood, body image, fear of kidney failure, life satisfaction, and decisional
      stability following living kidney donation: Findings from the KDOC study.
AB  - Prior studies demonstrate that most living kidney donors (LKDs) report no adverse
      psychosocial outcomes; however, changes in psychosocial functioning at the
      individual donor level have not been routinely captured. We studied psychosocial
      outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and
      20 healthy controls (HCs). There was minimal to no mood disturbance, body image
      concerns, fear of kidney failure, or life dissatisfaction, indicating no
      incremental changes in these outcomes over time and no significant differences
      between LKDs and HCs. The incidence of any new-onset adverse outcomes
      postdonation was as follows: mood disturbance (16%), fear of kidney failure
      (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable
      analyses demonstrated that LKDs with more mood disturbance symptoms, higher
      anxiety about future kidney health, low body image, and low life satisfaction
      prior to surgery were at highest risk of these same outcomes postdonation. It is
      important to note that some LKDs showed improvement in psychosocial functioning
      from pre- to postdonation. Findings support the balanced presentation of
      psychosocial risks to potential donors as well as the development of a donor
      registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up
      period in the United States.

PMID- 29206350
TI  - Isolated v-lesion in kidney transplant recipients: Characteristics, association
      with DSA, and histological follow-up.
AB  - Isolated v-lesion (IvL) represents a rare and challenging situation in renal
      allograft biopsies because it is unknown whether IvL truly represents rejection,
      antibody- or T cell-mediated, or not. This multicentric retrospective study
      describes the clinicopathological features of IvL with an emphasis on the donor
      specific antibody (DSA) status, histological follow-up, and graft survival.
      Inclusion criteria were the presence of v-lesion with minimal interstitial (i <=
      1) and microvascular inflammation (g + ptc<=1). C4d-positive biopsies were
      excluded. We retrospectively found 33 IvL biopsies in 33 patients, mainly
      performed in the early posttransplantation period (median time 27 days) and
      clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at
      the time of biopsy. IvL was treated by anti-rejection therapy in 21 cases
      (63.6%), whereas 12 (36.4%) were untreated. Seventy percent of untreated patients
      and 66% of treated patients showed favorable histological evolution on subsequent
      biopsy. Kidney graft survival in IvL was significantly higher than in a matched
      cohort of antibody-mediated rejection with arteritis. In conclusion, IvL is not
      primarily antibody-mediated and may show a favorable evolution. The heterogeneity
      of IvL pathophysiology on early biopsies should prompt DSA testing as well as
      close clinical and histological follow-up in all patients with IvL.

PMID- 29206351
TI  - Do all patients with renal cell carcinoma need a chest computed tomography?

PMID- 29206352
TI  - Anomalous observation with regard to prostate cancer in cancer research.

PMID- 29206353
TI  - Immortal-time bias: a crucial yet overlooked confounder in urological research.

PMID- 29206354
TI  - Combination treatments for overactive bladder refractory to first-line
      pharmacotherapy: do they meet expectations?

PMID- 29206355
TI  - From Novick to the NHS: the evolution of minimally-invasive nephron-sparing
      surgery.

PMID- 29206356
TI  - Formation and Isolation of a Four-Electron-Reduced Porphyrin Derivative by
      Reduction of a Stable 20pi Isophlorin.
AB  - The two-electron reduction of a diprotonated dodecaphenylporphyrin derivative by
      Na2 S2 O4 gave a corresponding isophlorin (Iph) selectively. Formation of Iph was
      confirmed by spectroscopic measurements and the isolation of tetramethylated Iph.
      Further reduction of Iph proceeded to form an unprecedented four-electron-reduced
      porphyrin (IphH2 ), which was fully characterized by spectroscopic and X-ray
      crystallographic analysis. IphH2 , with a unique conformation, could be oxidized
      to reproduce the starting porphyrin, resulting in a proton-coupled four-electron
      reversible redox system.

PMID- 29206358
TI  - Implementing and evaluating early intervention for children with autism: Where
      are the gaps and what should we do?
AB  - : Despite recent advances, the evidence base supporting early intervention for
      young children with autism spectrum disorder (ASD) remains relatively sparse. The
      International Society for Autism Research (INSAR) recently sponsored a Special
      Interest Group (SIG) on Implementing and Evaluating Community-Based Early
      Intervention. Across three meetings, in 2015, 2016, and 2017, conveners of this
      SIG engaged >200 members to identify knowledge gaps and research priorities for
      moving the field forward. Here, we summarize the perspectives that emerged from
      group discussion at the SIG meetings as represented by scholars working actively
      in the field. Despite encouraging progress, critical gaps and research priorities
      were identified across all the stages of intervention development and testing
      from conceptualization to community implementation. Key issues include the need
      for (a) formal theories to guide early intervention development, evaluation, and
      implementation; and alignment of intervention goals with scientific knowledge and
      societal changes that have occurred in the decades since interventions were
      originally developed; (b) increased focus on feasibility of treatment procedures
      and alignment with stakeholder values during pilot evaluations; (c) use of
      research designs that allow for comparisons of different interventions and
      formats, analyses of active ingredients of treatment, and identification of
      moderators and mediators of outcome; (d) use of community-partnered participatory
      research to guide adaptation of intervention models to community settings; (e)
      inclusion of constructs related to implementation processes and outcomes in
      treatment trials and; (f) an iterative approach to the progression of knowledge
      from intervention development to implementation. Autism Res 2018, 11: 16-23. (c)
      2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY
      SUMMARY: In this article, we summarize the themes discussed at the INSAR Special
      Interest Group (SIG) on Implementing and Evaluating Community-Based Early
      Intervention. Priorities for moving the field forward identified in the SIG
      included the need for (a) formal theories to guide the development and evaluation
      of interventions, (b) pilot evaluations that investigate feasibility and
      acceptability of interventions, (c) methodologies that allow us to determine for
      whom different interventions bring most benefit and why this is so, (d)
      strategies to include community members and other stakeholders in the process of
      developing and evaluating interventions, and (e) understanding of factors that
      make interventions more likely to be adopted and successfully implemented in the
      real world.

PMID- 29206357
TI  - Understanding uptake of an intervention to accelerate antiretroviral therapy
      initiation in Uganda via qualitative inquiry.
AB  - INTRODUCTION: The Streamlined Antiretroviral Therapy Initiation Strategy (START
      ART) study found that a theory-based intervention using opinion leaders to inform
      and coach health care providers about the risks of treatment delay, provision of
      point of care (POC) CD4 testing machines (PIMA) and reputational incentives, led
      to rapid rise in ART initiation. We used qualitative research methods to explore
      mechanisms of provider behaviour change. METHODS: We conducted in-depth
      interviews (IDIs) with 24 health care providers and nine study staff to
      understand perceptions, attitudes and the context of changes in ART initiation
      practices. Analyses were informed by the Theoretical Domains Framework. RESULTS:
      Rapid dissemination of new practices was enabled in the environmental context of
      an existing relationship based on communication, implementation and
      accountability between Makerere University Joint AIDS Program (MJAP), a Ugandan
      University-affiliated organization that provided technical oversight for HIV
      service delivery at the health facilities where the intervention was implemented,
      and a network of health facilities operated by the Uganda Ministry of Health.
      Coaching carried out by field coordinators from MJAP strengthened influence and
      informal accountability for carrying out the intervention. Frontline health
      workers held a pre-existing strong sense of professional identity. They were
      proud of attainment of new knowledge and skills and gratified by providing what
      they perceived to be higher quality care. Peer counsellors, who were not
      explicitly targeted in the intervention design, effectively substituted some
      functions of health care providers; as role models for successful ART uptake,
      they played a crucial role in creating demand for rapid ART initiation through
      interactions with patients. Point of care (POC) CD4 testing enabled immediate
      action and relieved providers from frustrations of lost or delayed laboratory
      results, and led to higher patient satisfaction (due to reduced costs because of
      ability to initiate ART right away, requiring fewer return trips to clinic).
      CONCLUSIONS: Qualitative data revealed that a multicomponent intervention to
      change provider behaviour succeeded in the context of strong institutional and
      individual relationships between a University-affiliated organization, government
      facilities, and peer health workers (who acted as a crucial link between
      stakeholders) and the community. Fostering stable institutional relationships
      between institutional actors (non-governmental organization (NGOs) and ministry
      operated facilities) as well as between facilities and the community (through
      peer health workers) can enhance uptake of innovations targeting the HIV cascade
      in similar clinical settings.

PMID- 29206359
TI  - Parent-infant co-sleeping and the implications for sudden infant death syndrome.
AB  - In 2015 the National Institute for Health and Care Excellence (NICE) updated its
      2006 guideline to clarify the association between parent infant co-sleeping and
      sudden infant death syndrome (SIDS). The practice of co-sleeping is a topic of
      continuing controversy and debate. Rather than highlighting the risks, the
      emphasis of the NICE guideline is to provide parents with balanced information so
      that they can make informed decisions about where their babies sleep. This
      contradicts previous public health messages on co-sleeping that discourages
      parents from the practice. Consequently, the updated national guideline has been
      criticised for failing to provide parents with safer sleep information, which has
      led to widespread confusion for parents and professionals. Health professionals
      can deliver safer sleep advice to support parents in their decision-making.
      However, as a result of inconsistent guidelines and evidence about parent-infant
      co-sleeping, health professionals may feel apprehensive and ill-equipped to
      provide advice and support. This article draws on a non-exhaustive literature
      review to discuss the risks and benefits of parent-infant co-sleeping, and the
      implications of this practice for SIDS. It also aims to provide transparency and
      improve understanding for health professionals so that they can support parents
      to adopt safer sleep strategies for their baby.

PMID- 29206360
TI  - Effect of a children's at-home nursing team on reducing emergency admissions.
AB  - This article explores the effect of a children's at-home nursing team, Hospital
      at Home (H@H), which aimed to reduce demand on acute hospital beds, support
      families to improve patient experience, and empower parents to care safely for
      their unwell children and help prevent emergency department (ED) reattendance.
      Data on demographics and clinical presentation of H@H and ED attendances were
      collected and compared. A survey measuring parents' confidence in managing their
      unwell children was also conducted. Of 72 patients treated by the H@H service
      between May and July 2016, 32 (44%) would have been admitted to hospital from the
      ED if the H@H service had not existed. This is equivalent to a saving of 64 bed
      days. Patients treated by the H@H service had similar demographics to those
      discharged from the ED to usual care. The H@H service took on patients with
      higher Bedside Paediatric Early Warning System scores before discharge. Parents
      reported that they would be more confident caring for their children after
      discharge from the H@H service. The H@H service decreased the number of
      unnecessary ED admissions. The service promotes a positive patient experience and
      increases parents' confidence when caring for unwell children at home.

PMID- 29206361
TI  - Service user involvement in preregistration child nursing programmes.
AB  - Service user involvement is a fundamental part of preregistration nursing
      education programmes, however achieving this for child nursing students is
      challenging. Service user involvement can be achieved through online forums but
      this method can lack the emotional interaction and opportunity for deep
      reflection. This article reviews the background and challenges of service user
      involvement in preregistration child nursing programmes, further exploring the
      evaluation of a group of final year child nursing students' experience of
      appreciating the journey of two service users. The input from service users
      provided the opportunity for reflection, empathy and improved student self
      awareness in nursing practice. Students gained perspective of the holistic needs
      of the service user, which empowered them to have confidence in their
      communication skills to ensure the voice of the child is heard and their rights
      are upheld. This article concludes that service user involvement is crucial in
      preregistration nursing programmes for the development of child nursing students,
      not only affecting their training but also the future workforce.

PMID- 29206362
TI  - Prevalence of neonate adhesive skin injuries in a Jordanian intensive care unit.
AB  - AIM: To determine the prevalence of adhesive skin injuries in neonates in a
      Jordanian neonatal intensive care unit (NICU) and to examine the characteristics
      of neonates with these injuries. METHOD: A cross-sectional period-prevalence
      study was conducted in a NICU in Irbid National University Hospital in Jordan. A
      total of 169 neonates were examined for skin injuries caused by adhesive
      equipment. RESULTS: The prevalence of skin injuries in this population was 26.6%.
      The injuries were located mostly on the face, arms, hands and chest, and were
      caused by endotracheal tubes, intravenous cannulae, fixation of nasogastric tubes
      and electrodes. Neonates with skin injuries were more likely to be preterm and
      underweight, to have respiratory problems and to have been connected to a
      mechanical ventilator. CONCLUSION: Adhesive skin injuries were found in more than
      one quarter of the neonates in this NICU and healthcare service providers should
      endeavour to minimise the occurrence of these injuries.

PMID- 29206363
TI  - In Their Own Words.

PMID- 29206364
TI  - Above the Atmosphere: Unique medical challenges for commercial space flight
      tourism.

PMID- 29206365
TI  - Stroke Detector: Ultrasound and telemedicine could allow paramedics to confirm
      stroke.

PMID- 29206366
TI  - Shocking Double: A review of what we know about double sequential external
      defibrillation.

PMID- 29206367
TI  - Gall Bladder Cancer.
AB  - Gallbladder carcinoma (GBC) is the most common biliary epithelial malignancy,
      with an estimated 10,910 new cases and 3700 deaths per year (Siegel et al. in CA
      Cancer J Clin 65:5-29, 2015 [1]). This disease's insidious nature and typically
      late presentation place it among the most lethal of invasive neoplasms.
      Gallbladder cancer spreads early by lymphatic or hematogenous metastasis and by
      direct invasion into the liver. While surgery may well be curative at early
      stages, both surgical and nonsurgical treatments remain largely unsuccessful in
      patients with more advanced disease.

PMID- 29206368
TI  - Diagnosis and Management of Intrahepatic and Extrahepatic Cholangiocarcinoma.
AB  - Cholangiocarcinomas (CC) are rare tumors which usually present late and are often
      difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or
      extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic
      CCs may be increasing worldwide. In this chapter, we review the risk factors,
      clinical presentation, and management of cholangiocarcinoma.

PMID- 29206369
TI  - Hepatocellular Carcinoma: Surgical Management and Evolving Therapies.
AB  - HCC is the second leading cause of cancer death worldwide. The majority of cases
      arise within the background of liver cirrhosis and are most commonly related to
      chronic hepatitis B and C viral infection. Surgical resection, liver
      transplantation, and tumour ablation are potentially curative modalities in cases
      of localized, non-metastatic, hepatocellular carcinoma. Systemic sorafenib has
      been shown to be marginally effective in slow disease progression in patients
      whose cirrhosis is so severe that they are not candidates for liver directed
      therapy and in those with metastatic disease. Several large prospective and
      retrospective studies have demonstrated transplantation to provide better long
      term outcomes than resection in patients with small volume carcinoma. Other small
      retrospective series have demonstrated similar outcomes for patients with well
      matched tumour characteristics and compensated cirrhosis. There is not even level
      one evidence to guide the choice of modality to be used in individual cases and
      treatment algorithms vary widely among high volume centres. Newer and emerging
      techniques and approaches such as laparoscopic liver resection and living donor
      transplantation continue to evolve and impact choice of treatment in absence of
      well-controlled comparative trials. For locally advanced disease and in patients
      with significant cirrhosis, interventional technologies such as transarterial
      chemoembolization or transarterial radioembolization can provide disease control
      or result in tumour regression and hypertrophy in the future liver remnant and
      may allow interval resection or down-staging to liver transplantation. Improving
      transarterial, surgical, and transplant techniques continue to expand the
      surgical and interventional options for managing localized HCC and are driving a
      shift towards aggressive multimodality therapy in patients with localized
      hepatoma.

PMID- 29206370
TI  - Clinical Features of Metastatic Hepatic Malignancies.
AB  - The liver is a common site for gastrointestinal tumor metastases as it is the
      first major organ reached by blood draining the portal venous system. With the
      development of more effective chemotherapeutic agents which may eradicate
      residual microscopic disease in the liver and help reduce known tumor burden,
      partial hepatectomy to remove gross metastatic disease will likely become
      increasingly utilized in the future. This chapter discusses the presentation and
      clinical factors in liver directed surgical resection.

PMID- 29206371
TI  - Editorial: Anthony J. Thomas Jr.

PMID- 29206372
TI  - Focal therapy will be the next step on prostate cancer management? | Opinion:
      Yes.

PMID- 29206374
TI  - Repeat Hepatectomy for Colorectal Liver Metastases.
AB  - Surgical resection of hepatic metastatic disease from colorectal cancer offers
      the best survival advantage when compared to other treatment modalities as
      survival from unresected disease is rare. Even after adequate surgical excision
      of colorectal cancer, 20-40 % of patients will develop recurrent disease to the
      liver. This chapter discusses the management of patients with recurrent
      colorectal metastases to the liver after initial resection and offers strategies
      to optimize and guide their treatment with a multimodality approach.

PMID- 29206373
TI  - Focal therapy will be the next step on prostate cancer management? | Opinion: No.

PMID- 29206375
TI  - Minimally Invasive Surgery of the Liver.
AB  - Operations on the liver have been undertaken for centuries for numerous
      indications including trauma, infections, and even for malignancy, but it was not
      until the past few decades that rates dramatically increased. This expanse in
      liver operations is due to a multitude of factors, including broader indications
      as well as improved safety. Our understanding of metastatic disease to the liver,
      especially colorectal cancer metastases, has vastly amplified the number of
      patients who would be candidates for hepatic resections and liver-directed
      therapies. We will focus our discussion here on planned minimally invasive
      operations for benign and malignant tumors as the majority of the literature
      relates to this setting.

PMID- 29206376
TI  - Locoregional Therapies for Primary and Secondary Hepatic Malignancies.
AB  - Management of hepatic malignancies is a multidisciplinary task with the
      involvement of hepatologists, medical/surgical oncologists, transplant surgeons,
      and interventional radiologists. The patients should be selected for a specific
      targeted therapy after multidisciplinary consensus. Interventional oncology has
      established its role in the management of hepatic malignancies. Image-guided
      locoregional therapies decrease the rate of systemic toxicity without
      compromising tumoricidal effect.

PMID- 29206377
TI  - Pathologic Features of Primary and Metastatic Hepatic Malignancies.
AB  - In the mammalian liver, 60 % of the cellular components are hepatocytes while the
      remainder (35 %) includes biliary epithelium, Kupffer cells, endothelial cells,
      fat storing cells and connective tissue cells. Although neoplasms of hepatocytes
      are the most common, a significant number of both benign and malignant primary
      liver neoplasms arising from other cell types can develop, such as tumors of bile
      duct epithelium (Table 1). In addition, the liver is one of the most susceptible
      sites for metastatic tumors arising from other organs of the body. Not too long
      ago, liver tumors were left untreated because the liver was considered a complex
      and mysterious organ inaccessible to surgery. Advances in imaging procedures and
      surgical techniques over the past 40 years have revolutionized the approaches to
      the treatment of benign and malignant liver tumors. Subsegmentectomy,
      segmentectomy, lobectomy, and transplantation are routinely performed for the
      treatment of primary and metastatic liver tumors with minimal morbidity and
      mortality. Since accurate diagnosis remains the key to clinical and surgical
      management, the emphasis of this chapter is on classification, morphological
      features and differential diagnosis of malignant neoplasms of the liver.

PMID- 29206378
TI  - Robotic Rectal Cancer Surgery.
AB  - There are an estimated 39,000 new cases of rectal cancer in the United States per
      year which makes it the third most prevalent cancer when paired with colon
      cancer. Given its complexity, there are now multiple modalities available for its
      successful treatment. This includes innovative chemotherapy, radiation, transanal
      resection techniques, and minimally invasive surgery. Robotic surgery for the
      treatment of rectal cancer represents the current pinnacle of minimally invasive
      technology for this disease process.

PMID- 29206379
TI  - Pet Patients: Assessment and treatment of dogs and cats involved in structure
      fires.

PMID- 29206380
TI  - Pathologic Features of Primary Colon, Rectal, and Anal Malignancies.
AB  - In the United States, colorectal cancer is the third most commonly diagnosed
      cancer in both men and women, as well as the third leading cause of cancer deaths
      (Colorectal cancer facts & figures 2014-2016, 2014 [2]). Worldwide, colorectal
      cancer is the fourth leading cause of death and causes almost 700,000 deaths each
      year (Cancer: fact sheet No. 297, 2015 [55]). This chapter discusses the clinical
      and pathologic features of the spectrum of epithelial, hematolymphoid, and
      mesenchymal malignant tumors of the colon, rectum, appendix, and anus.

PMID- 29206381
TI  - Importance of Adequate Lymphadenectomy in Gastrointestinal Cancer.
AB  - One of the most important factors influencing cancer-specific survival in the
      field GI oncology is the presence of positive lymph nodes. Although it remains
      controversial, adequate lymph node examination is required for accurate staging
      such that patients can receive correct adjuvant treatments and for stratification
      in clinical trials. Nevertheless, wide variation in the quality of lymph node
      examination exists in the US and many centers are not meeting guideline treatment
      recommendations.

PMID- 29206382
TI  - Bachelor's Benefits: The pros and cons of higher education as an EMS provider.

PMID- 29206383
TI  - Circulating Tumor Cells in Gastrointestinal Cancer: Current Practices and Future
      Directions.
AB  - GI cancers are the leading cause of cancer-related death worldwide primarily due
      to a combination of late presentation and aggressive biology. The lack of
      adequate biomarkers for screening, diagnosis, staging, and prognosis confounds
      clinical decision-making and delays potentially effective therapies. Circulating
      tumor cells (CTCs) are a new biomarker with particular promise in GI cancers,
      potentially offering clinicians and researchers real-time access to tumor tissue
      in a reliable, safe, and cost-effective manner. Preliminary studies have
      investigated the potential clinical utility of CTCs for all GI cancer types with
      promising results. Furthermore, advances in single cell analytics have been
      successfully applied to CTCs, allowing for exciting new clinical and research
      applications. In this chapter, we will review the current state of CTC research
      in GI cancers as well as the potential future applications that are currently
      being developed.

PMID- 29206384
TI  - Cost-Effectiveness Analysis in Cancer Care.
AB  - With the increasing complexity of modern medical therapies, it is becoming
      imperative to recognize the marginal cost and gains of increasingly sophisticated
      (and expensive) interventions. By understanding the incremental cost of a given
      intervention, investigators must help answer questions about healthcare resource
      utilization that are not answered by randomized clinical trials. The continued
      funding of biomedical research and pharmaceuticals will require more objective
      study of the return on investment for any given treatment modality, and cost
      effectiveness analyses will be instrumental in providing solutions to the
      inequalities in healthcare delivery.

PMID- 29206385
TI  - Vascular tangles: Recognizing and understanding arteriovenous malformations.

PMID- 29206386
TI  - Gastrointestinal Malignancy: Genetic Implications to Clinical Applications.
AB  - Alterations in the DNA sequences of genes, or mutations, have traditionally been
      viewed as the primary factors driving tumor progression, however, epigenetic
      evidence would suggest that some heritable traits are mediated by changes in DNA
      expression that are not dependent upon alterations in the primary DNA sequence.
      Advances in the genetic understanding of cancer have, in some instances, allowed
      for more precise administration of anti-neoplastic therapy. Targeted therapies,
      the aim of which are to target specific cellular proteins or processes used by
      the cancer cells, have been advocated to avoid the adverse side effects
      attributable to a lack of cell specificity associated with traditional
      chemotherapy. Here we aim to describe the current state of understanding
      regarding the genetic related causes of cancers, the targeted therapies aimed at
      killing them and the inter-relationship between these two.

PMID- 29206387
TI  - Zach's Story: An internal look at provider's AVM experience.

PMID- 29206393
TI  - Last Word: The Ups and downs of EMS.

PMID- 29206388
TI  - Hands on product reviews from street crews.

PMID- 29206394
TI  - Resuscitation Advances: Keep your mind (and your patient's cardiac flows) open.

PMID- 29206395
TI  - Evolving Care Standards: Stay current to avoid liability risk.

PMID- 29206396
TI  - Upgrade to EMS 3.0: Forthcoming document will guide the evolving role of EMS.

PMID- 29206397
TI  - Shortness of Breath: Standardized treatment doesn't work for all patients.

PMID- 29206398
TI  - Motorcross Malady: A look at alternative drugs for pain control in the field.

PMID- 29206400
TI  - Intubation Success: Study shows intubation success rate is higher with two-medic
      crews.

PMID- 29206399
TI  - Association between structural and functional brain alterations in drug-free
      patients with schizophrenia: a multimodal meta-analysis
AB  - Background: Neuroimaging studies have shown both structural and functional
      abnormalities in patients with schizophrenia. Recently, studies have begun to
      explore the association between structural and functional grey matter
      abnormalities. By conducting a meta--analysis on morphometric and functional
      imaging studies of grey matter alterations in drug-free patients, the present
      study aims to examine the degree of overlap between brain regions with anatomic
      and functional changes in patients with schizophrenia. Methods: We performed a
      systematic search of PubMed, Embase, Web of Science and the Cochrane Library to
      identify relevant publications. A multimodal analysis was then conducted using
      Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup
      and meta-regression analyses. Results: We included 15 structural MRI studies
      comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI
      studies comprising 403 drug-free patients and 428 controls in our meta-analysis.
      Drug-free patients were examined to reduce pharmacological effects on the imaging
      data. Multimodal analysis showed considerable overlap between anatomic and
      functional changes, mainly in frontotemporal regions, bilateral medial posterior
      cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left
      cerebellum. There were also brain regions showing only anatomic changes in the
      right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and
      functional alternations involving the right angular -gyrus. Limitations: The
      methodological aspects, patient characteristics and clinical variables of the
      included studies were heterogeneous, and we cannot exclude medication effects.
      Conclusion: The present study showed overlapping anatomic and functional brain
      abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug
      free patients with schizophrenia. However, the pattern of changes differed in
      these networks. Decreased grey matter was associated with decreased activation
      within the DMN, whereas it was associated with increased activation within the
      AN. These discrete patterns suggest different pathophysiological changes
      impacting structural and functional associations within different neural networks
      in patients with schizophrenia.

PMID- 29206401
TI  - Resuscitation outcomes consortium (ROC) studies dig deep into the science of CPR.

PMID- 29206402
TI  - And the Dead Shall Rise: Head-up CPR and the revolutionary research model used to
      develop it.

PMID- 29206403
TI  - Small Town, Big Commitment. Public safety agencies in Nebraska City, Neb., worked
      together to save their own.

PMID- 29206404
TI  - Evidence-Based Emphasis: Improving systems of care in time-sensitive emergencies.

PMID- 29206405
TI  - ?

PMID- 29206406
TI  - ?

PMID- 29206407
TI  - Caring for the Carers: Delivering peer-to-peer support and assessment following a
      traumatic incident.

PMID- 29206408
TI  - ?

PMID- 29206409
TI  - Special Needs in the Field: A guide to helping patients with disabilities.

PMID- 29206411
TI  - Hands On: Product Reviews From the Street Crews.

PMID- 29206410
TI  - The 5 Deadly Causes of Chest Pain: Recognizing the potentially lethal causes
      other than myocardial infarction.

PMID- 29206412
TI  - Essential Ingredients: Planting the seeds of leadership.

PMID- 29206413
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29206437
TI  - Ultralow-Threshold and Lightweight Biodegradable Porous PLA/MWCNT with Segregated
      Conductive Networks for High-Performance Thermal Insulation and Electromagnetic
      Interference Shielding Applications.
AB  - Lightweight, biodegradable, thermally insulating, and electrically conductive
      materials play a vital role in achieving the sustainable development of our
      society. The fabrication of such multifunctional materials is currently very
      challenging. Here, we report a general, facile, and eco-friendly way for the
      large-scale fabrication of ultralow-threshold and biodegradable porous polylactic
      acid (PLA)/multiwalled carbon nanotube (MWCNT) for high-performance thermal
      insulation and electromagnetic interference (EMI) shielding applications. Thanks
      to the unique structure of the microporous PLA matrix embedded by conductive 3D
      MWCNT networks, the lightweight porous PLA/MWCNT with a density of 0.045 g/cm3
      possesses a percolation threshold of 0.00094 vol %, which, to our knowledge, is
      the minimum value reported so far. Furthermore, the material exhibits excellent
      thermal insulation performance with a thermal conductivity of 27.5 mW.m-1.K-1,
      which is much lower than the best value of common thermal insulation materials.
      Moreover, it also shows outstanding EMI shielding performance characterized by
      its high shielding effectiveness (SE) values and absorption-dominated shielding
      feature. More importantly, its specific EMI SE is as high as 1010 dB.cm3.g-1,
      which is superior to those of other shielding materials reported so far. Thus,
      this novel multifunctional material and its general fabrication methodology
      provide a promising way to meet the growing demand for high-performance
      multifunctional materials in sustainable development.

PMID- 29206438
TI  - Corrosion Resistance of Nanosized Silicon Carbide-Rich Composite Coatings
      Produced by Noble Gas Ion Mixing.
AB  - Ion beam mixing has been used to produce a silicon carbide (SiC)-rich nanolayer
      for protective coating. Different C/Si/C/Si/C/Si(substrate) multilayer structures
      (with individual layer thicknesses falling in the range of 10-20 nm) have been
      irradiated by Ar+ and Xe+ ions at room temperature in the energy and fluence
      ranges of 40-120 keV and 1-6 * 1016 ion/cm2, respectively. The effects of ion
      irradiation, including the in-depth distribution of the SiC produced, was
      determined by Auger electron spectroscopy depth profiling. The thickness of the
      SiC-rich region was only some nanometers, and it could be tailored by changing
      the layer structure and the ion irradiation conditions. The corrosion resistance
      of the layers was investigated by potentiodynamic electrochemical test in 4 M KOH
      solution. The measured corrosion resistance of the SiC-rich layers was orders of
      magnitude better than that of pure silicon, and a correlation was found between
      the corrosion current density and the effective areal density of the SiC.

PMID- 29206439
TI  - Redox-Active Hydrogel Polymer Electrolytes with Different pH Values for Enhancing
      the Energy Density of the Hybrid Solid-State Supercapacitor.
AB  - To enhance the energy density of solid-state supercapacitors, a novel solid-state
      cell, made of redox-active poly(vinyl alcohol) (PVA) hydrogel electrolytes and
      functionalized carbon nanotube-coated cellulose paper electrodes, was
      investigated in this work. Briefly, acidic PVA-[BMIM]Cl-lactic acid-LiBr and
      neutral PVA-[BMIM]Cl-sodium acetate-LiBr hydrogel polymer electrolytes are used
      as catholyte and anolyte, respectively. The acidic condition of the catholyte
      contributes to suppression of the undesired irreversible reaction of Br- and
      extension of the oxygen evolution reaction potential to a higher value than that
      of the redox potential of Br-/Br3- reaction. The observed Br-/Br3- redox activity
      at the cathode contributes to enhance the cathode capacitance. The neutral
      condition of the anolyte helps extend the operating voltage window of the
      supercapacitor by introducing hydrogen evolution reaction overpotential to the
      anode. The electrosorption of nascent H on the negative electrode also increases
      the anode capacitance. As a result, the prepared solid-state hybrid
      supercapacitor shows a broad voltage window of 1.6 V, with a high Coulombic
      efficiency of 97.6% and the highest energy density of 16.3 Wh/kg with power
      density of 932.6 W/kg at 2 A/g obtained. After 10 000 cycles of galvanostatic
      charge and discharge tests at the current density of 10 A/g, it exhibits great
      cyclic stability with 93.4% retention of the initial capacitance. In addition, a
      robust capacitive performance can also be observed from the solid-state
      supercapacitor at different bending angles, indicating its great potential as a
      flexible energy storage device.

PMID- 29206440
TI  - Highly Efficient Broadband Yellow Phosphor Based on Zero-Dimensional Tin Mixed
      Halide Perovskite.
AB  - Organic-inorganic hybrid metal halide perovskites have emerged as a highly
      promising class of light emitters, which can be used as phosphors for optically
      pumped white light-emitting diodes (WLEDs). By controlling the structural
      dimensionality, metal halide perovskites can exhibit tunable narrow and broadband
      emissions from the free-exciton and self-trapped excited states, respectively.
      Here, we report a highly efficient broadband yellow light emitter based on zero
      dimensional tin mixed-halide perovskite (C4N2H14Br)4SnBrxI6-x (x = 3). This rare
      earth-free ionically bonded crystalline material possesses a perfect host-dopant
      structure, in which the light-emitting metal halide species (SnBrxI6-x4-, x = 3)
      are completely isolated from each other and embedded in the wide band gap organic
      matrix composed of C4N2H14Br-. The strongly Stokes-shifted broadband yellow
      emission that peaked at 582 nm from this phosphor, which is a result of excited
      state structural reorganization, has an extremely large full width at half
      maximum of 126 nm and a high photoluminescence quantum efficiency of ~85% at room
      temperature. UV-pumped WLEDs fabricated using this yellow emitter together with a
      commercial europium-doped barium magnesium aluminate blue phosphor
      (BaMgAl10O17:Eu2+) can exhibit high color rendering indexes of up to 85.

PMID- 29206441
TI  - Toward a Mechanistic Understanding of Vertical Growth of van der Waals Stacked 2D
      Materials: A Multiscale Model and Experiments.
AB  - Vertical stacking of monolayers via van der Waals (vdW) interaction opens
      promising routes toward engineering physical properties of two-dimensional (2D)
      materials and designing atomically thin devices. However, due to the lack of
      mechanistic understanding, challenges remain in the controlled fabrication of
      these structures via scalable methods such as chemical vapor deposition (CVD)
      onto substrates. In this paper, we develop a general multiscale model to describe
      the size evolution of 2D layers and predict the necessary growth conditions for
      vertical (initial + subsequent layers) versus in-plane lateral (monolayer)
      growth. An analytic thermodynamic criterion is established for subsequent layer
      growth that depends on the sizes of both layers, the vdW interaction energies,
      and the edge energy of 2D layers. Considering the time-dependent growth process,
      we find that temperature and adatom flux from vapor are the primary criteria
      affecting the self-assembled growth. The proposed model clearly demonstrates the
      distinct roles of thermodynamic and kinetic mechanisms governing the final
      structure. Our model agrees with experimental observations of various monolayer
      and bilayer transition metal dichalcogenides grown by CVD and provides a
      predictive framework to guide the fabrication of vertically stacked 2D materials.

PMID- 29206442
TI  - Fire-Retardant, Self-Extinguishing Inorganic/Polymer Composite Memory Foams.
AB  - Polymeric foams used in furniture and automotive and aircraft seating
      applications rely on the incorporation of environmentally hazardous fire
      retardant additives to meet fire safety norms. This has occasioned significant
      interest in novel approaches to the elimination of fire-retardant additives.
      Foams based on polymer nanocomposites or based on fire-retardant coatings show
      compromised mechanical performance and require additional processing steps. Here,
      we demonstrate a one-step preparation of a fire-retardant ice-templated
      inorganic/polymer hybrid that does not incorporate fire-retardant additives. The
      hybrid foams exhibit excellent mechanical properties. They are elastic to large
      compressional strain, despite the high inorganic content. They also exhibit
      tunable mechanical recovery, including viscoelastic "memory". These hybrid foams
      are prepared using ice-templating that relies on a green solvent, water, as a
      porogen. Because these foams are predominantly comprised of inorganic components,
      they exhibit exceptional fire retardance in torch burn tests and are self
      extinguishing. After being subjected to a flame, the foam retains its porous
      structure and does not drip or collapse. In micro-combustion calorimetry, the
      hybrid foams show a peak heat release rate that is only 25% that of a commercial
      fire-retardant polyurethanes. Finally, we demonstrate that we can use ice
      templating to prepare hybrid foams with different inorganic colloids, including
      cheap commercial materials. We also demonstrate that ice-templating is amenable
      to scale up, without loss of mechanical performance or fire-retardant properties.

PMID- 29206444
TI  - Multiregional Input-Output Analysis of Spatial-Temporal Evolution Driving Force
      for Carbon Emissions Embodied in Interprovincial Trade and Optimization Policies:
      Case Study of Northeast Industrial District in China.
AB  - In the counties with rapid economy and carbon emissions (CEs) growth, CEs
      embodied in interprovincial trade (CEs-PT) significantly impacts the CEs amount
      and structure and represents a key issue to consider in CEs reduction policies
      formulation. This study applied EEBT and two-stage SDA model to analyze the
      characteristics and driving force of spatial-temporal evolution for net CEs-PT
      outflow in the Northeast Industrial District of China (NID). We found that,
      during 1997-2007, the net CEs-PT flowed out from NID to 16 south and east
      provinces, then to 23 provinces all over China, and its amount has increased
      216.798Mt (by 211.67% per year). The main driving forces are technology and
      demand (further decomposed into structure and scale matrix); the contribution are
      71.6418 Mt and 145.1562 Mt. Then, we constructed coupling relationship model and
      took the top three industries with the greatest net CEs-PT outflow (farming,
      forestry, animal husbandry and fisheries, electricity and heat production and
      supply, petroleum processing, coking, and nuclear fuel processing) as examples,
      adjusted the interprovincial trade constructions, scales, and objects, to reduce
      the CEs-PT with lower costs, greater effect, and more equitability. The
      achievement could provide reference for formulating CEs reduction policies for
      similar areas in the world characterized by rapid growth of economy and CEs.

PMID- 29206443
TI  - Site-Specific 64Cu Labeling of the Serine Protease, Active Site Inhibited Factor
      Seven Azide (FVIIai-N3), Using Copper Free Click Chemistry.
AB  - A method for site-specific radiolabeling of the serine protease active site
      inhibited factor seven (FVIIai) with 64Cu has been applied using a biorthogonal
      click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein
      involved in hemostasis, angiogenesis, proliferation, cell migration, and survival
      of cancer cells. First a single azide moiety was introduced in the active site of
      this 50 kDa protease. Then a NOTA moiety was introduced via a strain promoted
      azide-alkyne reaction and the corresponding conjugate was labeled with 64Cu.
      Binding to TF and the stability was evaluated in vitro. TF targeting capability
      of the radiolabeled conjugate was tested in vivo by positron emission tomography
      (PET) imaging in pancreatic human xenograft cancer mouse models with various TF
      expressions. The conjugate showed good stability (>91% at 16 h), an
      immunoreactivity of 93.5%, and a mean tumor uptake of 2.1 +/- 0.2%ID/g at 15 h
      post injection. In conclusion, FVIIai was radiolabeled with 64Cu in single well
      defined position of the protein. This method can be utilized to prepare
      conjugates from serine proteases with the label at a specific position.

PMID- 29206445
TI  - Quantitation of a Therapeutic Antibody in Serum Using Intact Sequential Affinity
      Capture, Trypsin Digestion, and LC-MS/MS.
AB  - Large molecule quantitation by LC-MS/MS commonly relies on bottom-up or so-called
      surrogate peptide measurements to infer the whole-molecule concentration. This
      can lead to questions about what is actually being measured in the assay (intact
      drug and/or other drug related material). An intact sequential affinity capture
      (ISAC) assay was developed utilizing two different immunoaffinity (IA) reagents.
      The reagents were selective for the heavy and light chain of a monoclonal
      antibody, which when used consecutively, ensures that only the intact form of the
      antibody is represented by the surrogate peptide. The approach provided
      comparable results to a traditional sandwich IA assay indicating similar capture
      populations. The use of an initial ISAC assessment of affinity capture
      purification, should add a degree of confidence in the use of a single IA-LC
      MS/MS quantitation assay.

PMID- 29206446
TI  - Design of Complex Nanomaterials for Energy Storage: Past Success and Future
      Opportunity.
AB  - The development of next-generation lithium-based rechargeable batteries with high
      energy density, low cost, and improved safety is a great challenge with profound
      technological significance for portable electronics, electric vehicles, and grid
      scale energy storage. Specifically, advanced lithium battery chemistries call for
      a paradigm shift to electrodes with high Li to host ratio based on a conversion
      or alloying mechanism, where the increased capacity is often accompanied by
      drastic volumetric changes, significant bond breaking, limited electronic/ionic
      conductivity, and unstable electrode/electrolyte interphase. Fortunately, the
      rapid progress of nanotechnology over the past decade has been offering battery
      researchers effective means to tackle some of the most pressing issues for next
      generation battery chemistries. The major applications of nanotechnology in
      batteries can be summarized as follows: First, by reduction of the dimensions of
      the electrode materials, the cracking threshold of the material upon lithiation
      can be overcome, at the same time facilitating electron/ion transport within the
      electrode. Second, nanotechnology also provides powerful methods to generate
      various surface-coating and functionalization layers on electrode materials,
      protecting them from side reactions in the battery environment. Finally,
      nanotechnology gives people the flexibility to engineer each and every single
      component within a battery (separator, current collector, etc.), bringing novel
      functions to batteries that are unachievable by conventional methods. Thus, this
      Account aims to highlight the crucial role of nanotechnology in advanced battery
      systems. Because of the limited space, we will mainly assess representative
      examples of rational nanomaterials design with complexity for silicon and lithium
      metal anodes, which have shown great promise in constraining their large volume
      changes and the repeated solid-electrolyte interphase formation during cycling.
      Noticeably, the roadmap delineating the gradual improvement of silicon anodes
      with a span of 11 generations of materials designs developed in our group is
      discussed in order to reflect how nanotechnology could guide battery research
      step by step toward practical applications. Subsequently, we summarize efforts to
      construct nanostructured composite sulfur cathodes with improved electronic
      conductivity and effective soluble species encapsulation for maximizing the
      utilization of active material, cycle life, and system efficiency. We emphasize
      carbon-based materials and, importantly, materials with polar surfaces for sulfur
      entrapment. We then briefly discuss nanomaterials strategies to improve the ionic
      conductivity of solid polymer electrolytes by means of incorporating high-surface
      area and, importantly, high-aspect-ratio secondary-phase fillers for continuous,
      low-tortuosity ionic transport pathways. Finally, critical innovations that have
      been brought to the area of grid-scale energy storage and battery safety by
      nanotechnology are also succinctly reviewed.

PMID- 29206447
TI  - Collection Method for Isotopic Analysis of Gaseous Nitrous Acid.
AB  - The sources and chemistry of gaseous nitrous acid (HONO) in the environment are
      of great interest. HONO is a major source of atmospheric hydroxyl radical (OH),
      which impacts air quality and climate. HONO is also a major indoor pollutant that
      threatens human health. However, the large uncertainty of HONO sources and
      chemistry hinders an accurate prediction of the OH budget. Isotopic analysis of
      HONO may provide a tool for tracking the sources and chemistry of HONO. In this
      study, a modified annular denuder system (ADS) was developed to quantitatively
      capture HONO for offline nitrogen and oxygen isotopic analysis (delta15N and
      delta18O) using the denitrifier method. The ADS method was tested using
      laboratory generated HONO (400 ppbv to 1 ppmv) and validated by parallel HONO
      collection with a standard, basic impinger (BI) method. The ADS system shows
      complete capture of HONO without isotopic fractionation. The uncertainty (1sigma)
      based on repeated measurements across the entire analytical procedure is 0.60/00
      for delta15N and 0.50/00 for delta18O. The ADS method was also tested in roadside
      collections of ambient HONO (0.4-1.3 ppbv) for isotopic analysis and was found to
      be robust for low concentration collections over 3 and 12 h collection times. In
      order to ensure ability to use this method in the laboratory and in the field,
      storage conditions for the collected HONO samples were tested and samples can be
      stored with consistent delta15N and delta18O for 60 days. This method enables
      future work to utilize the isotopic composition of HONO for studying HONO
      chemical formation pathways, as well as atmospheric sources and chemistry.

PMID- 29206448
TI  - Ni-Al Bimetallic Catalyzed Enantioselective Cycloaddition of Cyclopropyl
      Carboxamide with Alkyne.
AB  - A Ni-Al bimetallic catalyzed enantioselective cycloaddition reaction of
      cyclopropyl carboxamides with alkynes has been developed. A series of
      cyclopentenyl carboxamides were obtained in up to 99% yield and 94% ee. The
      bifunctional-ligand-enabled bimetallic catalysis proved to be an efficient
      strategy for the C-C bond cleavage of unreactive cyclopropanes.

PMID- 29206449
TI  - Key Roles of Size and Crystallinity of Nanosized Iron Hydr(oxides) Stabilized by
      Humic Substances in Iron Bioavailability to Plants.
AB  - Availability of Fe in soil to plants is closely related to the presence of humic
      substances (HS). Still, the systematic data on applicability of iron-based
      nanomaterials stabilized with HS as a source for plant nutrition are missing. The
      goal of our study was to establish a connection between properties of iron-based
      materials stabilized by HS and their bioavailability to plants. We have prepared
      two samples of leonardite HS-stabilized iron-based materials with substantially
      different properties using the reported protocols and studied their physical
      chemical state in relation to iron uptake and other biological effects. We used
      Mossbauer spectroscopy, XRD, SAXS, and TEM to conclude on iron speciation, size,
      and crystallinity. One material (Fe-HA) consisted of polynuclear iron(III)
      (hydr)oxide complexes, so-called ferric polymers, distributed in HS matrix. These
      complexes are composed of predominantly amorphous small-size components (<5 nm)
      with inclusions of larger crystalline particles (the mean size of (11 +/- 4) nm).
      The other material was composed of well-crystalline feroxyhyte (delta'-FeOOH) NPs
      with mean transverse sizes of (35 +/- 20) nm stabilized by small amounts of HS.
      Bioavailability studies were conducted on wheat plants under conditions of iron
      deficiency. The uptake studies have shown that small and amorphous ferric
      polymers were readily translocated into the leaves on the level of Fe-EDTA,
      whereas relatively large and crystalline feroxyhyte NPs were mostly sorbed on the
      roots. The obtained data are consistent with the size exclusion limits of cell
      wall pores (5-20 nm). Both samples demonstrated distinct beneficial effects with
      respect to photosynthetic activity and lipid biosynthesis. The obtained results
      might be of use for production of iron-based nanomaterials stabilized by HS with
      the tailored iron availability to plants. They can be applied as the only source
      for iron nutrition as well as in combination with the other elements, for
      example, for industrial production of "nanofortified" macrofertilizers (NPK).

PMID- 29206450
TI  - Widely Applicable Hydrofluorination of Alkenes via Bifunctional Activation of
      Hydrogen Fluoride.
AB  - Expanding the use of fluorine in pharmaceuticals, agrochemicals and materials
      requires a widely applicable and more efficient protocol for the preparation of
      fluorinated compounds. We have developed a new generation nucleophilic
      fluorination reagent, KHSO4-13HF, HF 68 wt/wt %, that is not only easily handled
      and inexpensive but also capable of hydrofluorinating diverse, highly
      functionalized alkenes, including natural products. The high efficiency observed
      in this reaction hinges on the activation of HF using a highly "acidic" hydrogen
      bond acceptor.

PMID- 29206451
TI  - Correction to Understanding the Scarcity of Thorium Peroxide Clusters.

PMID- 29206452
TI  - Magnetic Structure of Density Matrices.
AB  - The spin structure of wave functions is reflected in the magnetic structure of
      the one-particle density matrix. Indeed, for single determinants we can use
      either one to determine the other. In this work we discuss how one can simply
      examine the one-particle density matrix to faithfully determine whether the spin
      magnetization density vector field is collinear, coplanar, or noncoplanar. For
      single determinants, this test suffices to distinguish collinear determinants
      which are eigenfunctions of Sn from noncollinear determinants which are not. We
      also point out the close relationship between noncoplanar magnetism on the one
      hand and complex conjugation symmetry breaking on the other. Finally, we use
      these ideas to classify the various ways single determinant wave functions break
      and respect symmetries of the Hamiltonian in terms of their one-particle density
      matrix.

PMID- 29206453
TI  - Exploring the Accuracy of a Low Scaling Similarity Transformed Equation of Motion
      Method for Vertical Excitation Energies.
AB  - The newly developed back transformed pair natural orbital based similarity
      transformed equation of motion (bt-STEOM) method at the coupled cluster singles
      and doubles level (CCSD) is combined with an appropriate modification of our
      earlier active space selection scheme for STEOM. The resulting method is
      benchmarked for valence, Rydberg, and charge transfer excited states of Thiel's
      test set and other test systems. The bt-PNO-STEOM-CCSD method gives very similar
      results to canonical STEOM-CCSD for both singlet and triplet excited states. It
      performs in a balanced manner for all these types of excited states, while the
      EOM-CCSD method performs especially well for Rydberg excited states and the CC2
      method excels at obtaining accurate results for valence excited states. Both EOM
      CCSD and CC2 perform worse than bt-PNO-STEOM-CCSD for charge transfer states for
      the test cases studied.

PMID- 29206454
TI  - Direct Access to Highly Functionalized Heterocycles through the Condensation of
      Cyclic Imines and alpha-Oxoesters.
AB  - A facile, gram-scale preparation of 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3
      ones and 2-hydroxy-6,7,8,8a-tetrahydroindolizin-3(5H)-ones from a condensation
      cyclization of alpha-oxoesters with five- and six-membered cyclic imines,
      respectively, is reported. This transformation enables a concise, three-step
      synthesis of the natural products phenopyrrozin and p-hydroxyphenopyrrozin.
      Further, biologically relevant scaffolds, such as alpha-quaternary beta-homo
      prolines and beta-lactams, are also prepared in two- to three-steps from the
      versatile 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one core.

PMID- 29206455
TI  - Reversible Insertion of a C?C Bond into Magnesium(I) Dimers: Generation of Highly
      Active 1,2-Dimagnesioethane Compounds.
AB  - The insertion of 1,1-diphenylethylene into the Mg-Mg bond of two magnesium(I)
      dimers, [(ArNacnac)Mg-]2 (Ar = C6H2Me3-2,4,6 (Mes); C6H3Et2-2,6 (Dep)), yielding
      1,2-dimagnesioethane products, [{(ArNacnac)Mg}2(MU-CH2CPh2)], is described. These
      reactions are readily reversible at room temperature and thus represent the first
      examples of room-temperature reversible redox processes for s-block metal
      complexes. The 1,2-dimagnesioethane products are highly activated magnesium
      alkyls and show unprecedented, uncatalyzed reactivity toward H2, CO, and
      ethylene. Computational studies have investigated the mechanisms of all presented
      reaction types.

PMID- 29206457
TI  - ADVERPred-Web Service for Prediction of Adverse Effects of Drugs.
AB  - Application of structure-activity relationships (SARs) for the prediction of
      adverse effects of drugs (ADEs) has been reported in many published studies.
      Training sets for the creation of SAR models are usually based on drug label
      information which allows for the generation of data sets for many hundreds of
      drugs. Since many ADEs may not be related to drug consumption, one of the main
      problems in such studies is the quality of data on drug-ADE pairs obtained from
      labels. The information on ADEs may be included in three sections of the drug
      labels: "Boxed warning," "Warnings and Precautions," and "Adverse reactions." The
      first two sections, especially Boxed warning, usually contain the most frequent
      and severe ADEs that have either known or probable relationships to drug
      consumption. Using this information, we have created manually curated data sets
      for the five most frequent and severe ADEs: myocardial infarction, arrhythmia,
      cardiac failure, severe hepatotoxicity, and nephrotoxicity, with more than 850
      drugs on average for each effect. The corresponding SARs were built with PASS
      (Prediction of Activity Spectra for Substances) software and had balanced
      accuracy values of 0.74, 0.7, 0.77, 0.67, and 0.75, respectively. They were
      implemented in a freely available ADVERPred web service (
      http://www.way2drug.com/adverpred/ ), which enables a user to predict five ADEs
      based on the structural formula of compound. This web service can be applied for
      estimation of the corresponding ADEs for hits and lead compounds at the early
      stages of drug discovery.

PMID- 29206456
TI  - Real-Time Conformational Changes and Controlled Orientation of Native Proteins
      Inside a Protein Nanoreactor.
AB  - Protein conformations play crucial roles in most, if not all, biological
      processes. Here we show that the current carried through a nanopore by ions
      allows monitoring conformational changes of single and native substrate-binding
      domains (SBD) of an ATP-Binding Cassette importer in real-time. Comparison with
      single-molecule Forster Resonance Energy Transfer and ensemble measurements
      revealed that proteins trapped inside the nanopore have bulk-like properties. Two
      ligand-free and two ligand-bound conformations of SBD proteins were inferred and
      their kinetic constants were determined. Remarkably, internalized proteins
      aligned with the applied voltage bias, and their orientation could be controlled
      by the addition of a single charge to the protein surface. Nanopores can thus be
      used to immobilize proteins on a surface with a specific orientation, and will be
      employed as nanoreactors for single-molecule studies of native proteins.
      Moreover, nanopores with internal protein adaptors might find further practical
      applications in multianalyte sensing devices.

PMID- 29206458
TI  - A Versatile Approach to Attachment of Triarylmethyl Labels to DNA for Nanoscale
      Structural EPR Studies at Physiological Temperatures.
AB  - Triarylmethyl (trityl, TAM) radicals are a promising class of spin labels for
      nanometer-scale distance measurements in biomolecules at physiological
      temperatures. However, to date, existing approaches to site-directed TAM labeling
      of DNA have been limited to label attachment at the termini of oligonucleotides,
      thus hindering a majority of demanded applications. Herein, we report a new
      versatile strategy for TAM attachment at arbitrary sites of nucleic acids. It
      utilizes an achiral non-nucleoside phosphoramidite monomer for automated solid
      phase synthesis of oligonucleotides, which are then postsynthetically
      functionalized with TAM. We demonstrate a synthesis of a set of oligonucleotide
      complexes that are TAM-labeled at internal or terminal sites, as well as the
      possibility of measuring interspin distances up to ~5-6 nm at 298 K using double
      quantum coherence electron paramagnetic resonance (EPR). Implementation of the
      developed approach strongly broadens the scope of nucleic acids and nucleoprotein
      complexes available for nanoscale structural EPR studies at room temperatures.

PMID- 29206459
TI  - Photochemistry of the H2O/CO System Revisited: The HXeOH...CO Complex in a Xenon
      Matrix.
AB  - We report on the complex of a noble-gas hydride HXeOH with carbon monoxide. This
      species is prepared via the annealing-induced H + Xe + OH...CO reaction in a
      xenon matrix, the OH...CO complexes being produced by VUV photolysis of the
      H2O...CO complexes. The H-Xe stretching mode of the HXeOH...CO complex absorbs at
      1590.3 cm-1 and it is blue-shifted by 12.7 cm-1 from the H-Xe stretching band of
      HXeOH monomer. The observed blue shift indicates the stabilization of the H-Xe
      bond upon complexation, which is characteristic of complexes of noble-gas
      hydrides. The HXeOH...CO species is the first complex of a noble-gas hydride with
      carbon monoxide and the second observed complex of HXeOH. On the basis of the
      MP2/aug-cc-pVTZ-PP calculations, the experimental complex is assigned to the
      structure, where the carbon atom of CO interacts with the oxygen atom of HXeOH.

PMID- 29206460
TI  - Complex Dynamics of Water in Protein Confinement.
AB  - This paper studies single-molecule and collective dynamics of water confined in
      protein powders by means of molecular dynamics simulations. The single-particle
      dynamics show a modest retardation compared to the bulk but become highly
      stretched in the powder, with the stretching exponent of ?0.2. The collective
      dynamics of the total water dipole are affected by intermolecular correlations
      inside water and by cross-correlations between the water and the protein. The
      dielectric spectrum of water in the powder has two nearly equal-amplitude peaks:
      a Debye peak with ?16 ps relaxation time and a highly stretched peak with the
      relaxation time of ?13 ns and a stretching exponent of ?0.12. The slower
      relaxation component is not seen in the single-molecule correlation functions and
      can be assigned to elastic protein motions displacing water in the powder. The
      loss spectrum of the intermediate scattering function reported by neutron
      scattering experiments is also highly stretched, with the high-frequency wing
      scaling according to a power law. Translational dynamics can become much slower
      in the powder than in the bulk but are overshadowed by the rotational loss in the
      overall loss spectrum of neutron scattering.

PMID- 29206461
TI  - First-Principles Study of Dissociation Processes for the Synthesis of Fe and Co
      Oxide Nanoparticles.
AB  - Thermal decomposition is a practical and reliable tool to synthesize
      nanoparticles with monodisperse size distribution and reproducible accuracy. The
      nature of the precursor molecules and their interaction with the environment
      during the synthesis process have a direct impact on the resulting nanoparticles.
      Our study focuses on widely used transition-metal (Co, Fe) stearates precursors
      and their thermal decomposition reaction pathway. We show how the nature of the
      metal and the presence or absence of water molecules, directly related to the
      humidity conditions during the synthesis process, affect the decomposition
      mechanism and the resulting transition-metal oxide building blocks. This, in
      turn, has a direct effect on the physical and chemical properties of the produced
      nanoparticles and deeply influences their composition and morphology.

PMID- 29206463
TI  - Rigorous pKa Estimation of Amine Species Using Density-Functional Tight-Binding
      Based Metadynamics Simulations.
AB  - Predicting pKa values for different types of amine species with high accuracy and
      efficiency is of critical importance for the design of high performance and
      economical solvents in carbon capture and storage with aqueous amine solutions.
      In this study, we demonstrate that density-functional tight-binding-based
      metadynamics simulations are a promising approach to calculate the free energy
      difference between the protonated and neutral states of amines in aqueous
      solution with inexpensive computational cost. The calculated pKa values were in
      satisfactory agreement with the experimental values, the mean absolute deviation
      being only 0.09 pKa units for 34 amines commonly used in CO2 scrubbing. Such
      superior reproducibility and correlation compared to estimations by static
      quantum mechanical calculations highlight the significant effect of dynamical
      proton transfer processes in explicit solvent molecules for the improvement of
      the estimation accuracy.

PMID- 29206462
TI  - Lipidomics Reveals Dramatic Physiological Kinetic Isotope Effects during the
      Enzymatic Oxygenation of Polyunsaturated Fatty Acids Ex Vivo.
AB  - Arachidonic acid (AA, 20:4) is an omega-6 polyunsaturated fatty acid (PUFA) and
      the main precursor to the class of lipid mediators known as eicosanoids. The
      enzymes that catalyze the oxygenation of AA begin by abstracting hydrogen from
      one of three bis-allylic carbons within 1,4-cis,cis-diene units. Substitution of
      deuterium for hydrogen has been shown to lead to massive kinetic isotope effects
      (KIE) for soybean lipoxygenase (sLOX) oxygenation of linoleic acid (LA, 18:2).
      Yet, experimental determination of the KIE during oxygenation of AA and LA by
      mammalian enzymes including cyclooxygenase (COX) and lipoxygenase (LOX) has
      revealed far lower values. All prior studies investigating the KIE of PUFA
      oxygenation have relied on in vitro systems using purified enzymes and were
      limited by availability of deuterated substrates. Here we demonstrate the use of
      macrophages as an ex vivo model system to study the physiological KIE (PKIE)
      during enzymatic AA oxygenation by living cells using a newly synthesized library
      of deuterated AA isotopologues. By extending lipidomic UPLC-MS/MS approaches to
      simultaneously quantify native and deuterated lipid products, we were able to
      demonstrate that the magnitude of the PKIE measured in macrophages for COX and
      LOX oxygenation of AA is similar to KIEs determined in previous reports using the
      AA isotopologue deuterated at carbon 13 (C13). However, for the first time we
      show that increasing the number of deuterated bis-allylic carbons to include both
      C10 and C13 leads to a massive increase in the PKIE for COX oxygenation of AA. We
      provide evidence that hydrogen(s) present at C10 of AA play a critical role in
      the catalysis of prostaglandin and thromboxane synthesis. Furthermore, we
      discovered that deuteration of C10 promotes the formation of the resolving lipid
      mediator lipoxin B4, likely by interfering with AA cyclization and shunting AA to
      the LOX pathway under physiological conditions.

PMID- 29206464
TI  - Ring-Opening Diarylation of Siloxydifluorocyclopropanes by Ag(I) Catalysis:
      Stereoselective Construction of 2-Fluoroallylic Scaffold.
AB  - A silver-catalyzed, defluorination ring-opening diarylation of siloxy 2,2
      difluorocyclopropanes, with two arenes, to directly prepare polysubstituted 2
      fluoroallylic compounds, is described. This multicomponent reaction proceeds
      smoothly in good stereoselectivity, which is due to a chelation-controlled
      addition of arenes to alpha-fluorinated ketone intermediate.

PMID- 29206465
TI  - Testing the Equivalence between Spatial Averaging and Temporal Averaging in
      Highly Dilute Solutions.
AB  - Diffusion relates the flux of particles to the local gradient of the particle
      density in a deterministic way. The question arises as to what happens when the
      particle density is so low that the local gradient becomes an ill-defined
      concept. The dilemma was resolved early last century by analyzing the average
      motion of particles subject to random forces whose magnitude is such that the
      particles are always in thermal equilibrium with their environment. The diffusion
      dynamics is now described in terms of the probability density of finding a
      particle at some position and time and the probabilistic flux density, which is
      proportional to the gradient of the probability density. In a time average sense,
      the system thus behaves exactly like the ensemble average. Here, we report on an
      experimental method and test this fundamental equivalence principle in
      statistical physics. In the experiment, we study the flux distribution of 20 nm
      radius polystyrene particles impinging on a circular sink of micrometer
      dimensions. The particle concentration in the water suspension is approximately 1
      particle in a volume element of the dimension of the sink. We demonstrate that
      the measured flux density is exactly described by the solution of the diffusion
      equation of an infinite system, and the flux statistics obeys a Poissonian
      distribution as expected for a Markov process governing the random walk of
      noninteracting particles. We also rigorously show that a finite system behaves
      like an infinite system for very long times despite the fact that a finite system
      converges to a zero flux empty state.

PMID- 29206466
TI  - Doping of Self-Catalyzed Nanowires under the Influence of Droplets.
AB  - Controlled and reproducible doping is essential for nanowires (NWs) to realize
      their functions. However, for the widely used self-catalyzed vapor-liquid-solid
      (VLS) growth mode, the doping mechanism is far from clear, as the participation
      of the nanoscale liquid phase makes the doping environment highly complex and
      significantly different from that of the thin film growth. Here, the doping
      mechanism of self-catalyzed NWs and the influence of self-catalytic droplets on
      the doping process are systematically studied using beryllium (Be) doped GaAs
      NWs. Be atoms are found for the first time to be incorporated into NWs
      predominantly through the Ga droplet that is observed to be beneficial for
      setting up thermodynamic equilibrium at the growth front. Be dopants are thus
      substitutional on Ga sites and redundant Be atoms are accumulated inside the Ga
      droplets when NWs are saturated, leading to the change of the Ga droplet
      properties and causing the growth of phase-pure zincblende NWs. This study is an
      essential step toward the design and fabrication of nanowire devices.

PMID- 29206467
TI  - Structural Transformation of LiFePO4 during Ultrafast Delithiation.
AB  - The prolific lithium battery electrode material lithium iron phosphate (LiFePO4)
      stores and releases lithium ions by undergoing a crystallographic phase change.
      Nevertheless, it performs unexpectedly well at high rate and exhibits good
      cycling stability. We investigate here the ultrafast charging reaction to resolve
      the underlying mechanism while avoiding the limitations of prevailing
      electrochemical methods by using a gaseous oxidant to deintercalate lithium from
      the LiFePO4 structure. Oxidizing LiFePO4 with nitrogen dioxide gas reveals
      structural changes through in situ synchrotron X-ray diffraction and electronic
      changes through in situ UV/vis reflectance spectroscopy. This study clearly shows
      that ultrahigh rates reaching 100% state of charge in 10 s does not lead to a
      particle-wide union of the olivine and heterosite structures. An extensive solid
      solution phase is therefore not a prerequisite for ultrafast charge/discharge.

PMID- 29206468
TI  - Frequency-Domain Proof of the Existence of Atomic-Scale SERS Hot-Spots.
AB  - The existence of sub-nanometer plasmonic hot-spots and their relevance in
      spectroscopy and microscopy applications remain elusive despite a few recent
      theoretical and experimental evidence supporting this possibility. In this
      Letter, we present new spectroscopic evidence suggesting that Angstrom-sized hot
      spots exist on the surfaces of plasmon-excited nanostructures. Surface-enhanced
      Raman scattering (SERS) spectra of 4,4'-biphenyl dithiols placed in metallic
      junctions show simultaneously blinking Stokes and anti-Stokes spectra, some of
      which exhibit only one prominent vibrational peak. The activated vibrational
      modes were found to vary widely between junction sites. Such site-specific,
      single-peak spectra could be successfully modeled using single-molecule SERS
      induced by a hot-spot with a diameter no larger than 3.5 A, located at the
      specific molecular sites. Furthermore, the model, which assumes the stochastic
      creation of hot-spots on locally flat metallic surfaces, consistently reproduces
      the intensity distributions and occurrence statistics of the blinking SERS peaks,
      further confirming that the sources of the hot-spots are located on the metallic
      surfaces. This result not only provides compelling evidence for the existence of
      Angstrom-sized hot-spots but also opens up the new possibilities for the
      vibrational and electronic control of single-molecule photochemistry and real
      space visualization of molecular vibration modes.

PMID- 29206469
TI  - Chiral Metamaterials of Plasmonic Slanted Nanoapertures with Symmetry Breaking.
AB  - We propose a universal design scheme for a new type of chiral metamaterials based
      on plasmonic slanted nanoapertures simply milled in a single metal layer. Strong
      optical chirality is introduced by tilting nanoapertures with almost arbitrary
      shape along a certain direction to break all the mirror symmetries. As a typical
      example, chiral metamaterial based on slanted split-ring apertures is
      demonstrated with giant circular dichroism in transmission (CDT) over 78% at 760
      nm. We reveal that the high CDT originates from the circularly dichroic mode
      coupling process in the slanted nanoapertures induced by spin-dependent field
      overlap conditions. Furthermore, tunable CDT is presented through the in-plane
      rotation of nanoapertures to form chiral images with controllable image contrast.
      Besides, chiral metamaterials with slanted nanoapertures of two other shapes
      including L-shaped aperture and rectangular aperture are also presented with
      large circular dichroism. We envision that our demonstrated chiral metamaterials
      enable promising platforms for a variety of applications in nonlinear optics,
      chiral imaging and sensing, spectroscopy, and polarization manipulation.

PMID- 29206470
TI  - Csp2-Csp2 and Csp2-N Bond Formation in a One-Pot Reaction between N
      Tosylhydrazones and Bromonitrobenzenes: An Unexpected Cyclization to Substituted
      Indole Derivatives.
AB  - A novel, sequential, palladium-catalyzed, cross-coupling reaction using N
      tosylhydrazone and bromonitrobenzene derivatives followed by reductive
      cyclization has been developed. This transformation providing an efficient route
      to unexpected N-arylindole derivatives involves, in a one-pot reaction, the
      formation of one Csp2-Csp2 bond and two Csp2-N bonds together with the cleavage
      of one Csp2-heteroatom bond. Evaluation of the biological activity led to the
      identification of compound 5a, which displays potent activity at nanomolar
      concentrations against human colon carcinoma cell line.

PMID- 29206471
TI  - Optical Forces at the Nanoscale: Size and Electrostatic Effects.
AB  - The reduced magnitude of the optical trapping forces exerted over sub-200 nm
      dielectric nanoparticles complicates their optical manipulation, hindering the
      development of techniques and studies based on it. Improvement of trapping
      capabilities for such tiny objects requires a deep understanding of the
      mechanisms beneath them. Traditionally, the optical forces acting on dielectric
      nanoparticles have been only correlated with their volume, and the size has been
      traditionally identified as a key parameter. However, the most recently published
      research results have shown that the electrostatic characteristics of a sub-100
      nm dielectric particle could also play a significant role. Indeed, at present it
      is not clear what optical forces depend. In this work, we designed a set of
      experiments in order to elucidate the different mechanism and properties (i.e.,
      size and/or electrostatic properties) that governs the magnitude of optical
      forces. The comparison between experimental data and numerical simulations have
      shown that the double layer induced at nanoparticle's surface, not considered in
      the classical description of nanoparticle's polarizability, plays a relevant role
      determining the magnitude of the optical forces. Here, the presented results
      constitute the first step toward the development of the dielectric nanoparticle
      over which enhanced optical forces could be exerted, enabling their optical
      manipulation for multiples purposes ranging from fundamental to applied studies.

PMID- 29206472
TI  - Synergistic Enhancement of Electron-Accepting and -Donating Ability of
      Nonconjugated Polymer Nanodot in Micellar Environment.
AB  - Understanding the fundamental electron-transfer dynamics in photoactive carbon
      nanoparticles (CNPs) is vitally important for their fruitful application in
      photovoltaics and photocatalysis. Herein, photoinduced electron transfer (PET) to
      and from the nonconjugated polymer nanodot (PND), a new class of luminescent CNP,
      has been investigated in the presence of N,N-dimethylaniline (DMA) and methyl
      viologen (MV2+) in homogeneous methanol and sodium dodecyl sulfate (SDS)
      micelles. It has been observed that both DMA and MV2+ interact with the
      photoexcited PND and quench the PL intensity as well as excited-state lifetime in
      bulk methanol. While in bulk methanol, purely diffusion-controlled PET from DMA
      to MV2+ via PND has been observed, the mechanism and dynamics differ
      significantly in SDS micelles. In contrast to homogeneous methanol medium, a
      distinct synergic effect has been observed in SDS micelles. The presence of both
      DMA and MV2+ enhances the electron-accepting and -donating abilities of PND in
      SDS micelles. Time-resolved photoluminescence (PL) measurements reveal that the
      PET process in SDS micelles is nondiffusive in nature mainly due to instantaneous
      electron transfer at the confined micellar surface. These results have been
      explained on the basis of heterogeneous microenvironments of SDS micelles which
      compartmentalize the donor and acceptor inside its micellar pseudo phase. The
      present findings provide valuable insights into the intrinsic relation between
      redox and PL properties of nonconjugated PND.

PMID- 29206473
TI  - Carbonyl Iron Powder: A Reagent for Nitro Group Reductions under Aqueous Micellar
      Catalysis Conditions.
AB  - An especially mild, safe, efficient, and environmentally responsible reduction of
      aromatic and heteroaromatic nitro-group-containing educts is reported that
      utilizes very inexpensive carbonyl iron powder (CIP), a highly active commercial
      grade of iron powder. These reductions are conducted in the presence of
      nanomicelles composed of TPGS-750-M in water, a recyclable aqueous micellar
      reaction medium. This new technology also shows broad scope and scalability and
      presents opportunities for multistep one-pot sequences involving this reducing
      agent.

PMID- 29206474
TI  - Trace lithium in Texas tap water is negatively associated with all-cause
      mortality and premature death.
AB  - Lithium in tap water was previously found to have life-extending effects across
      18 Japanese municipalities. Using a larger dataset with several Texas counties,
      our study shows that lithium concentrations in tap water are negatively
      associated with all-cause mortality (r = -0.18, p = 0.006, 232 counties) and
      years of potential life lost (r = -0.22, p = 0.001, 214 counties). Thus, our
      present findings extend and reinforce lithium's purported life-prolonging effect
      in humans.

PMID- 29206475
TI  - Whole-Blood Gene Expression in Pulmonary Nontuberculous Mycobacterial Infection.
AB  - The factors predisposing toward the development of pulmonary nontuberculous
      mycobacterial (pNTM) disease and influencing disease progression remain unclear.
      Impaired immune responses have been reported in individuals with pNTM disease,
      but data are limited and inconsistent. In this study, we sought to use gene
      expression profiling to examine the host response to pNTM disease. Microarray
      analysis of whole-blood gene expression was performed on 25 subjects with pNTM
      disease and 27 uninfected control subjects with respiratory disease. Gene
      expression results were compared with phenotypic variables and survival data.
      Compared with uninfected control subjects, pNTM disease was associated with
      downregulation of 213 transcripts enriched for terms related to T cell signaling,
      including IFNG. Reduced IFNG expression was associated with more severe computed
      tomography changes and impaired lung function. Mortality was associated with the
      expression of transcripts related to the innate immune response and inflammation,
      whereas transcripts related to T and B cell function were associated with
      improved survival. These findings suggest that pNTM disease is associated with an
      aberrant immune response, which may reflect an underlying propensity to infection
      or result from NTM infection itself. There were important differences in the
      immune response associated with survival and mortality in pNTM disease.

PMID- 29206476
TI  - Systemic Markers of Adaptive and Innate Immunity Are Associated with Chronic
      Obstructive Pulmonary Disease Severity and Spirometric Disease Progression.
AB  - The progression of chronic obstructive pulmonary disease (COPD) is associated
      with marked alterations in circulating immune cell populations, but no studies
      have characterized alterations in these cell types across the full spectrum of
      lung function impairment in current and former smokers. In 6,299 subjects from
      the COPDGene and ECLIPSE (Evaluation of COPD Longitudinally to Identify
      Predictive Surrogate Endpoints) studies, we related Coulter blood counts and
      proportions to cross-sectional forced expiratory volume in 1 second (FEV1),
      adjusting for current smoking status. We also related cell count measures to 3
      year change in FEV1 in ECLIPSE subjects. In a subset of subjects with blood gene
      expression data, we used cell type deconvolution methods to infer the proportions
      of immune cell subpopulations, and we related these to COPD clinical status. We
      observed that FEV1 levels are positively correlated with lymphocytes and
      negatively correlated with myeloid populations, such as neutrophils and
      monocytes. In multivariate models, absolute cell counts and proportions were
      associated with cross-sectional FEV1, and lymphocytes, monocytes, and eosinophil
      counts were predictive of 3-year change in lung function. Using cell type
      deconvolution to study immune cell subpopulations, we observed that subjects with
      COPD had a lower proportion of CD4+ resting memory cells and naive B cells
      compared with smokers without COPD. Alterations in circulating immune cells in
      COPD support a mixed pattern of lymphocyte suppression and an enhanced myeloid
      cell immune response. Cell counts and proportions contribute independent
      information to models predicting lung function, suggesting a critical role for
      immune response in long-term COPD outcomes. Cell type deconvolution is a
      promising method for immunophenotyping in large cohorts.

PMID- 29206477
TI  - Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management.
AB  - Acute eosinophilic pneumonia (AEP) is an uncommon acute respiratory illness of
      varying severity that includes presentation as acute respiratory distress
      syndrome with fatal outcome. AEP may be idiopathic, but identifiable causes
      include smoking and other inhalational exposures, medications, and infections.
      The pathogenesis of AEP is poorly understood but likely varies depending on the
      underlying cause. Airway epithelial injury, endothelial injury, and release of IL
      33 are early events that subsequently promote eosinophil recruitment to the lung;
      eosinophilic infiltration and degranulation appear to mediate subsequent lung
      inflammation and associated clinical manifestations. Crucial for the diagnosis
      are the demonstration of pulmonary eosinophilia in the BAL fluid and the
      exclusion of other disease processes that can present with acute pulmonary
      infiltrates. Although peripheral blood eosinophilia at initial presentation may
      be a clue in suggesting the diagnosis of AEP, it may be absent or delayed,
      especially in smoking-related AEP. Optimal management of AEP depends on the
      recognition and elimination of the underlying cause when identifiable. The
      cessation of the exposure to the inciting agent (e.g., smoking), and
      glucocorticoids represent the mainstay of treating AEP of noninfectious origin.
      If AEP is recognized and treated in a timely manner, the prognosis is generally
      excellent, with prompt and complete clinical recovery, even in those patients
      manifesting acute respiratory failure.

PMID- 29206478
TI  - Lactate is oxidized outside of the mitochondrial matrix in rodent brain.
AB  - The nature and existence of mitochondrial lactate oxidation is debated in the
      literature. Obscuring the issue are disparate findings in isolated mitochondria,
      as well as relatively low rates of lactate oxidation observed in permeabilized
      muscle fibres. However, respiration with lactate has yet to be directly assessed
      in brain tissue with the mitochondrial reticulum intact. To determine if lactate
      is oxidized in the matrix of brain mitochondria, oxygen consumption was measured
      in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex
      and hippocampus (dorsal) subregions. While respiration in the presence of ADP and
      malate increased with the addition of lactate, respiration was maximized
      following the addition of exogenous NAD+, suggesting maximal lactate metabolism
      involves extra-matrix lactate dehydrogenase. This was further supported when NAD+
      dependent lactate oxidation was significantly decreased with the addition of
      either low-concentration alpha-cyano-4-hydroxycinnamate or UK-5099, inhibitors of
      mitochondrial pyruvate transport. Mitochondrial respiration was comparable
      between glutamate, pyruvate, and NAD+-dependent lactate oxidation. Results from
      the current study demonstrate that permeabilized brain is a feasible model for
      assessing lactate oxidation, and support the interpretation that lactate
      oxidation occurs outside the mitochondrial matrix in rodent brain.

PMID- 29206479
TI  - Microencapsulation of esterified krill oil, using complex coacervation.
AB  - The microencapsulation of the esterified krill oil (EKO), obtained from the
      transesterification of krill oil (KO) with 3,4-dihydroxyphenylacetic acid (DHPA),
      via complex coacervation and was investigated. The experimental findings showed
      that the DHPA and phenolic lipids (PLs) in the EKO affected the stability of the
      gelatine (GE)-EKO emulsion. To improve its stability, the effects of varying the
      pH of GE and the use of two emulsification devices, including the homogeniser and
      ultrasonic liquid processor were investigated, where the ultrasonic liquid
      processor was found to be a relatively more appropriate emulsification device. In
      addition, the capsules prepared using a pH of GE of 8.0 showed superior storage
      and had significantly (p <0.05) lower peroxide value as compared to those
      prepared with a pH of GE of 6.5. The microencapsulation of the EKO was effective
      in delaying the development of oxidation products during a period of 25 d of
      storage, at 25  degrees C.

PMID- 29206480
TI  - Soil microbial communities of three grassland ecosystems in the Bayinbuluke,
      China.
AB  - The microbial community plays an important role in soil nutrient cycles and
      energy transformations in alpine grassland. In this study, we investigated the
      composition of the soil microbial community collected from alpine cold swamp
      meadow (ASM), alpine cold meadow (AM), and alpine cold desert steppe (ADS) within
      the Bayinbuluke alpine grassland, China, using Illumina amplicon sequencing. Of
      the 147 271 sequences obtained, 36 microbial phyla or groups were detected. The
      results showed that the ADS had lower microbial diversity than the ASM and AM, as
      estimated by the Shannon index. The Verrucomicrobia, Chloroflexi, Planctomycetes,
      Proteobacteria, and Actinobacteria were the predominant phyla in all 3
      ecosystems. Particularly, Thaumarchaeota was only abundant in ASM, Bacteroidetes
      in AM, and Acidobacteria in ADS. Additionally, the predominant genus also
      differed with each ecosystem. Candidatus Nitrososphaera was predominant in ADS,
      the Pir4 lineage in ASM, and Sphingomonas in AM. Our results indicated that the
      soil microbial community structure was different for each grassland ecosystem in
      the Bayinbuluke.

PMID- 29206481
TI  - Age, memory loss and perceptions of dementia in South Asian ethnic minorities.
AB  - BACKGROUND: South Asian older adults are represented less frequently in
      mainstream mental health services or those for people with dementia. This study
      aimed to explore in detail the perceptions of dementia (symptoms, causes,
      consequences, treatments) held by South Asians and to discern how these
      understandings vary by age and by the self-recognition of memory problems, as
      these influence help-seeking behaviour. METHODS: Participants were allocated to
      three groups: younger adults; older adults; and older adults with subjective
      memory problems. They completed the semi-structured Barts Explanatory Model
      Inventory for Dementia schedule, whilst older adults also completed measures of
      cognition (MMSE), and depression (GDS). Interviews were conducted in English,
      Gujarati or Urdu. RESULTS: Groups were similar in identifying unusual forgetting
      and confusion as the most frequent symptoms; stress and age as the most frequent
      causes; and talking to your GP/nurse, taking medication, and talking to family
      and friends as the most frequent treatments. Younger adults more often knew about
      risk factors and reported practical consequences more than older adults. Older
      adults with subjective memory problems were more likely to describe sleep related
      problems or symptoms commonly associated with depression. They more often cited
      as causes of dementia lack of sleep, side effects of medication and medical
      reasons, and mentioned religion as a means to cope. CONCLUSIONS: Findings
      highlight variability in perceptions of dementia across the South Asian Community
      and identify specific areas where dementia awareness could be raised in South
      Asian sub-groups to improve timely diagnosis, treatment outcomes and service
      access.

PMID- 29206482
TI  - Brain circuits and neurochemical systems in essential tremor: insights into
      current and future pharmacotherapeutic approaches.
AB  - INTRODUCTION: There are few medications that are available for the treatment of
      essential tremor (ET) and they are only moderately effective. Areas covered: Data
      were obtained from a PubMed search. Original articles, review articles, and
      clinical guidelines were included. Two disease models for ET have been proposed:
      1) the olivary model, which attributes ET to a pathological pacemaker in the
      inferior olivary nucleus, and 2) the cerebellar degeneration model, which
      postulates that ET originates in the cerebellum and could be related to deficient
      or abnormal Purkinje cell (PC) output. Underlying biochemical dysfunction in T
      type calcium channels (T-tCaC) may loosely be linked to the first model and
      deficiency/abnormality in gamma-aminobutyric acid (GABA) neurotransmission, to
      the second. Expert commentary: Human data points robustly to the role of GABA in
      ET. Numerous medications that target the GABA system have been tried, with
      variable success. Given the many different types of GABA-ergic neurons, and the
      multitude of GABAA receptor subtypes, a given medication could have
      competing/cancelling effects. It would seem that influencing GABA receptors
      broadly is not as effective as targeting certain GABAA receptor subtypes. Future
      research should seek to identify molecular candidates that have a more targeted
      effect within the GABA system.

PMID- 29206484
TI  - A high-fat diet is deleterious to mice under glycolysis restriction.
AB  - It is debated whether carbohydrate restriction has metabolic advantage for its
      variable weight loss. Five-week-old male mice fed a high-fat diet and receiving a
      glycolytic inhibitor, 2-deoxyglucose, died within 9 days. They exhibited greater
      decreases in rectal temperature, appetite, and decline in body weight accompanied
      by increasing total cholesterol level than the other groups. This study suggests
      that carbohydrate is necessary for adequate physical and metabolic performance
      when lipid-rich diet is loaded.

PMID- 29206483
TI  - Positron emission tomography in Parkinson's disease: insights into impulsivity.
AB  - This study reviews previous studies that employ positron emission tomography
      (PET) imaging assessments in Parkinson's disease (PD) patients with and without
      Impulsive Compulsive Behaviours (ICB). This begins with a summary of the
      potential benefits and limitations of commonly utilized ligands, specifically
      D2/3 receptor and dopamine transporter ligands. Since previous findings emphasize
      the role of the ventral striatum in the manifestation of ICBs, this study
      attempts to relate these imaging findings to changes in behaviour, especially
      emphasizing work performed in substance abuse and addiction. Next, it reviews how
      increasing disease duration in PD can influence dopamine receptor expression,
      with an emphasis on differential striatal and extra-striatal changes that occur
      along the course of PD. Finally, it focuses on how extra-striatal changes,
      particularly in the orbitofrontal cortex, amygdala, and anterior cingulate, may
      influence the proficiency of behavioural regulation in PD. The discussion
      emphasizes the interaction of disease and medication effects on network-wide
      changes that occur in PD, and how these changes may result in behavioural
      dysregulation.

PMID- 29206485
TI  - Structure and Measurement Invariance of Adult Romantic Attachment.
AB  - Romantic attachment is a popular theory for explaining affect, cognition, and
      behavior in romantic contexts. This popularity has led to a surge of self-report
      measures assessing dimensions of attachment. In this study, we considered the
      ability of 2 common attachment measures, the Adult Attachment Questionnaire (AAQ)
      and the Experience in Close Relationships-Revised (ECR-R), to replicate the
      avoidant and anxious attachment factors. We also determined the degree of
      measurement invariance across, and mean differences between, genders and single
      and nonsingle individuals. Both the AAQ (N = 650) and the ECR-R (N = 1,271)
      successfully distinguished avoidant and attachment factors. The AAQ showed
      evidence for partial strong measurement invariance, whereas the ECR-R showed
      strict factorial invariance for both gender and relationship status. Gender
      differences were detected on both measures in a direction consistent with
      previous research, with males exhibiting higher levels of avoidant attachment
      (relative to females) and females exhibiting higher levels of anxious attachment
      (relative to males). Furthermore, when compared to individuals who were currently
      single, those in romantic relationships exhibited lower levels of avoidant
      tendencies. This research aligns with the notion that the AAQ and ECR-R reliably
      assess similar constructs, across genders and single and nonsingle individuals.

PMID- 29206486
TI  - The method of chicken whole embryo culture using the eggshell windowing,
      surrogate eggshell and ex ovo culture system.
AB  - 1. The unique accessibility of the avian embryo have made them an ideal model for
      the study of development and genome editing. Chicken whole embryo culture has
      provided important insights into toxicity tests, gene manipulation, clarifying
      gene functions, cell transplantation and cell tracking. 2. A simple technique for
      chicken manipulation is eggshell windowing, without or with seal, the latter
      having demonstrated some improvement in hatching rates. 3. Likewise, a surrogate
      eggshell system provides an accessible model for manipulation during chicken and
      quail development, with a higher hatchability compared to the simple windowing
      method. 4. The development of the chicken ex ovo culture systems in a synthetic
      environment as an efficient technique for imaging and microsurgery applications
      has enabled the study of important events of live chicken embryos at a specific
      time point. 5. This short review illustrates recent applications of well-designed
      whole embryo culture systems as a robust model for research into numerous
      biological mechanism, drug discovery, gene manipulating and production of
      functional proteins.

PMID- 29206487
TI  - Role of catechins on ET-1-induced stimulation of PLD and NADPH oxidase activities
      in pulmonary smooth muscle cells: determination of the probable mechanism by
      molecular docking studies.
AB  - The treatment of human pulmonary artery smooth muscle cells with ET-1 stimulates
      the activity of PLD and NADPH oxidase, but this stimulation is inhibited by
      pretreatment with bosentan (ET-1 receptor antagonist), FIPI (PLD inhibitor),
      apocynin (NADPH oxidase inhibitor), and EGCG and ECG (catechins having a galloyl
      group), but not EGC and EC (catechins devoid of a galloyl group). Herein, using
      molecular docking analyses based on our biochemical studies, we determined the
      probable mechanism by which the catechins containing a galloyl group inhibit the
      stimulation of PLD activity induced by ET-1. The ET-1-induced stimulation of PLD
      activity was inhibited by SecinH3 (inhibitor of cytohesin). Arf6 and cytohesin-1
      are associated in the cell membrane, which is not inhibited by the catechins
      during ET-1 treatment of the cells. However, EGCG and ECG inhibited the binding
      of GTPgammaS with Arf6, even in the presence of cytohesin-1. The molecular
      docking analyses revealed that the catechins containing a galloyl group (EGCG and
      ECG) with cytohesin-1-Arf6GDP, but not the catechins without a galloyl group (EGC
      and EC), prevent GDP-GTP exchange in Arf6, which seems to be an important
      mechanism for inhibiting the activation of PLD induced by ET-1, and subsequently
      increases the activity of NADPH oxidase.

PMID- 29206489
TI  - Continuous flow technology vs. the batch-by-batch approach to produce
      pharmaceutical compounds.
AB  - INTRODUCTION: For the manufacture of small molecule drugs, many pharmaceutical
      innovator companies have recently invested in continuous processing, which can
      offer significant technical and economic advantages over traditional batch
      methodology. This Expert Review will describe the reasons for this interest as
      well as many considerations and challenges that exist today concerning continuous
      manufacturing. Areas covered: Continuous processing is defined and many reasons
      for its adoption are described. The current state of continuous drug substance
      manufacturing within the pharmaceutical industry is summarized. Current key
      challenges to implementation of continuous manufacturing are highlighted, and an
      outlook provided regarding the prospects for continuous within the industry.
      Expert commentary: Continuous processing at Lilly has been a journey that started
      with the need for increased safety and capability. Over twelve years the original
      small, dedicated group has grown to more than 100 Lilly employees in discovery,
      development, quality, manufacturing, and regulatory designing in continuous drug
      substance processing. Recently we have focused on linked continuous unit
      operations for the purpose of all-at-once pharmaceutical manufacturing, but the
      technical and business drivers that existed in the very beginning for stand-alone
      continuous unit operations in hybrid processes have persisted, which merits
      investment in both approaches.

PMID- 29206488
TI  - Structural and functional evidence for the scaffolding effect of alveolar blood
      vessels.
AB  - A contribution of pulmonary blood distension to alveolar opening was first
      proposed more than 100 years ago. To investigate the contribution of blood
      distension to lung mechanics, we studied control mice (normal perfusion), mice
      after exsanguination (absent perfusion) and mice after varying degrees of
      parenchymal resection (supra-normal perfusion). On inflation, mean tracheal
      pressures were higher in the bloodless mouse (4.0 +/- 2.5 cm H2O); however, there
      was minimal difference between conditions on deflation (0.7 +/- 0.9 cm H2O). To
      separate the peripheral and central mechanical effects of blood volume, multi
      frequency lung impedance data was fitted to the constant-phase model. The
      presence or absence of blood had no effect on central airway resistance (p >
      .05). In contrast, measures of tissue damping (G), tissue elastance (H) and
      hysteresivity (eta) demonstrated a significant increase in bloodless mice
      relative to control mice (p < .001). After varying amount of surgical resection
      and associated supra-normal perfusion of the remaining lung, there was an
      increase in G and H. Although the absolute difference in G and H increased with
      the amount of parenchymal resection, the proportional contribution of blood was
      identical in all conditions. The presence of blood in the pulmonary vasculature
      resulted in a constant 64 +/- 5% reduction in tissue damping (G) and a 55 +/- 4%
      reduction in tissue elastance (H). This nearly-constant contribution of blood to
      lung hysteresivity was only reduced by positive end-expiratory pressure (PEEP).
      To identify a distinct structural subset of vessels in the lung potentially
      contributing to these observations, vascular casting and scanning electron
      microscopy of the lung demonstrated morphologically distinct vascular rings at
      the alveolar opening. Our results suggest that intravascular blood distension,
      likely attributable to a subset of vessels in the alveolar entrance ring,
      contributes a measurable scaffolding effect to the functional recruitment of the
      peripheral lung.

PMID- 29206491
TI  - New advances in tau imaging in parkinsonism.
AB  - Currently, the differential diagnosis between atypical parkinsonisms and
      classical idiopathic Parkinson's disease can be quite difficult because of the
      significant overlap of clinical presentation and symptoms. Neurodegenerative
      conditions, including progressive supranuclear palsy (PSP), corticobasal
      degeneration (CBD), and frontotemporal dementia (FTD), are primarily
      characterized by accumulation of tau protein in the brain. Recent imaging
      developments for tau pathology may provide a promising tool for the assessment of
      diagnosis, prognosis, and progression of these neurodegenerative disorders. This
      review will survey PET studies to describe the recent advances in the imaging of
      tau pathology in PSP, CBD, and FTD.

PMID- 29206492
TI  - Intravenous controlled-release hydrogen sulfide protects against ventilator
      induced lung injury.
AB  - BACKGROUND: Despite its critical utility in providing life support to patients
      with impaired respiratory functions, prolonged mechanical ventilation has been
      found to cause a series of pathological changes in the lung that are collectively
      referred to as ventilator-induced lung injury (VILI). This study aims to
      investigate the therapeutic effects of mesoporous silica nanoparticles (DATS
      MSN), which is capable of releasing H2S in a slow and controlled manner, on VILI.
      METHODS: A murine VILI model was generated. Rats were randomly divided to three
      equal groups, the DATS-MSN group, the ventilation group and the nonventilated
      control group. The animals in both the DATS-MSN group and the ventilation group
      were surgically connected to rodent ventilators. Meanwhile, the DATS-MSN group
      and the ventilation group were administered intravenously with 50 mg/kg DATS-MSN
      and physiological saline, respectively. Animal mortality and various
      physiological parameters of the lung were recorded throughout the experiment
      period. Upon completion, the rats were sacrificed and lung tissues were collected
      for histological examination. The levels of various pro- and anti-inflammatory
      cytokines in the bronchoalveolar lavage fluid were quantified. The protein levels
      of NF-kappaB, total and phosphorylated IkappaB-alpha in lung tissues were
      determined by Western blotting. RESULTS: The rats in the ventilation group showed
      severe lung injuries and impaired respiratory functions as evidenced by decreased
      tension of oxygen in arterial blood. However, the injection of DATS-MSN was found
      to significantly mitigate these abnormalities. In addition, DATS-MSN could
      significantly alleviate ventilator-induced up-regulation of several pro
      inflammatory proteins, such as TNF-alpha, IL-1alpha/beta and IL-2, in the murine
      lung tissues, while stimulating the expression of IL-4, an anti-inflammatory
      cytokine. Lastly, the nanoparticles were demonstrated to decrease NF-kappaB
      activity in lung tissues by inhibiting IkappaB-alpha phosphorylation and
      degradation. CONCLUSION: The current study provided preliminary evidence that
      intravenous administration of DATS-MSN, a controlled-release H2S donor, led to
      prolonged survival, improved lung function and alleviated the inflammatory
      response to mechanical ventilation in a murine model.

PMID- 29206493
TI  - Understanding and Diagnosing Antimicrobial Resistance on Social Media: A Yearlong
      Overview of Data and Analytics.
AB  - To better understand user conversations revolving around antibiotics and
      antimicrobial resistance (AMR) on Twitter, we used an online data collection and
      analysis toolkit with full firehose access to collect corpuses of tweets with
      "antibiotic" and "antimicrobial resistance" keyword tracks. The date range
      included tweets from November 28, 2015, to November 25, 2016, for both datasets.
      This yearlong date range provides insight into how users have discussed
      antibiotics and AMR and identifies any spikes in activity during a particular
      time frame. Overall, we found that discussions about antibiotics and AMR
      predominantly occur in the United States and the United Kingdom, with roughly
      equal gender participation. These conversations are influenced by news sources,
      health professionals, and governmental health organizations. Users will often
      defer to retweet and recirculate content posted from these official sources and
      link to external articles instead of posting their own musings on the subjects.
      Our findings are important benchmarks in understanding the prevalence and reach
      of potential misinformation about antibiotics and AMR on Twitter.

PMID- 29206494
TI  - Prenatal Diagnosis of Twin Fetuses with a Novel AR Gene Mutation in a Chinese
      Family of Complete Androgen Insensitivity Syndrome.
AB  - INTRODUCTION AND AIMS: Androgen insensitivity syndrome (AIS) is an X-linked
      recessive genetic disorder caused by mutations in the androgen receptor (AR)
      gene. Only a few cases of AIS with AR gene mutations have been diagnosed
      prenatally. This study aimed to investigate the gene mutation in a Chinese
      complete androgen insensitivity syndrome family and perform prenatal diagnosis
      for twin fetuses. CASE REPORT: We evaluated the AR gene of the child proband in a
      Chinese CAIS family, and detected a novel mutation c.3864T>C (p. Phe917Leu).
      Amniocentesis was performed when the mother presented to our hospital with a
      subsequent twin pregnancy. Mutation analysis revealed that both fetuses were
      hemizygous for this mutation. The aborted fetuses had typical female external
      genitalia and bilateral testes in abdomen. CONCLUSION: The c.3864T>C AR novel
      mutation is responsible for complete androgen insensitivity syndrome, and its
      identification was subsequently used for a subsequent successful prenatal
      diagnosis.

PMID- 29206495
TI  - The Clinical and Pathological Features of Maternal Gastric Adenocarcinoma
      Metastatic to Placenta.
AB  - We describe two mothers with metastatic gastric carcinoma involving the placenta.
      The first was a 35-year-old woman, who presented with a progressive decline in
      serum fibrinogen level at 34 + 2gestation week and underwent an emergency
      cesarean section. The second case was a 30-year-old woman who developed
      intolerable lumbosacral pain and cesarean section was performed at her 37 +
      3gestation week. Gross pathological examinations of both placentas were normal,
      but microscopy showed poorly differentiated adenocarcinoma infiltration in the
      intervillous space, later proved to be gastric in origin. The neoplastic cells
      did not involve the villi, but were associated with massive perivillous fibrin.
      The two mothers died 180 and 19 days after the delivery. Both babies were free of
      metastatic carcinoma at 20- and 19-month follow-up.

PMID- 29206496
TI  - Development of solid dispersions of beta-lapachone in PEG and PVP by solvent
      evaporation method.
AB  - beta-lapachone (betalap) has shown potential use in various medical applications.
      However, its poor solubility has limited its systemic administration and clinical
      applications. The aim of this work is to develop solid dispersions of betalap
      using poly (ethylene glycol) (PEG 6000) and polyvinylpyrrolidone (PVP K30) as
      hydrophilic polymers and evaluate the dissolution rate in aqueous medium. Solid
      dispersions were prepared by solvent evaporation method using different weight
      ratios of betalap and hydrophilic polymer (1:1, 1:2, and 1:3). Characterization
      performed by differential scanning calorimetry, Fourier transform infrared
      spectroscopy, X-ray diffraction, and scanning electron microscopy showed that
      betalap was molecularly dispersed within the polymer matrix. The in vitro
      dissolution tests showed an enhancement in the dissolution profile of betalap as
      solid dispersions prepared in both PVP and PEG, although the former showed better
      results. The drug:polymer ratio influenced betalap dissolution rate, as higher
      amounts of hydrophilic polymer led to enhanced drug dissolution. Thus, this study
      demonstrated that solid dispersions of betalap in PVP offers an effective way to
      overcome the poor dissolution of betalap.

PMID- 29206497
TI  - Computer assisted surgery in preoperative planning of acetabular fracture
      surgery: state of the art.
AB  - INTRODUCTION: The development of imaging modalities and computer technology
      provides a new approach in acetabular surgery. Areas covered: This review
      describes the role of computer-assisted surgery (CAS) in understanding of the
      fracture patterns, in the virtual preoperative planning of the surgery and in the
      use of custom-made plates in acetabular fractures with or without 3D printing
      technologies. A Pubmed internet research of the English literature of the last 20
      years was carried out about studies concerning computer-assisted surgery in
      acetabular fractures. The several steps for CAS in acetabular fracture surgery
      are presented and commented by the main author regarding to his personal
      experience. Expert commentary: Computer-assisted surgery in acetabular fractures
      is still initial experiences with promising results. Patient-specific
      biomechanical models considering soft tissues should be developed to allow a more
      realistic planning.

PMID- 29206498
TI  - The potential application of strategic released apigenin from polymeric carrier
      in pulmonary fibrosis.
AB  - AIM: The capability of reducing fibrotic and inflammatory responses in lung
      tissues represents a gold standard for evaluating the efficacy of therapeutic
      interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of
      therapeutic strategies have been employed in clinic to treat PF, but limited
      success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of
      flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this
      study, we explore the potential therapeutic effect of apigenin in lung fibrosis.
      MATERIALS AND METHODS: Apigenin was employed to treat IPF in a bleomycin-induced
      PF rat model. Apigenin was loaded onto a biodegradable polymer carrier
      (nanoparticle, NP) to improve its bio-solubility and bio-availability. The
      properties (e.g. size, apigenin loading and release profile) of the apigenin
      loaded polymer carrier were well-characterized. In vitro study was performed to
      assess the impact of apigenin on pulmonary cell viability, growth, as well as
      inflammatory and pro-fibrosis responses in pulmonary cells. The impact of
      apigenin on the production of inflammatory cytokines (e.g. TGF-beta, TNF-alpha)
      and pro-fibrosis factors in bronchoalveolar lavage fluid and pulmonary cells from
      lung tissues was also investigated. RESULTS: Our results showed, apigenin has
      anti-fibrosis effect by inhibition fibrosis related cytokines expression. And
      compared with apigenin in soluble form, the strategic release of apigenin is more
      effective in inhibiting pulmonary fibrosis and inflammation. CONCLUSION: Our
      finding suggested that apigenin loaded on polymeric carrier might be an effective
      treatment for pulmonary fibrosis patients.

PMID- 29206499
TI  - Expert judgment based multicriteria decision models to assess the risk of
      pesticides on reproduction failures of grey partridge.
AB  - A suite of models is proposed for estimating the risk of pesticides against the
      grey partridge (Perdix perdix) and their clutches. Radio-tracked data of females,
      description and location of the clutches, and data on the pesticide treatments
      during the laying periods of the partridges were used as basic information.
      Quantitative structure-activity relationship (QSAR) and quantitative structure
      property relationship (QSPR) modelling allowed us to characterize the pesticides
      by their 1-octanol/water partition coefficient (log P), vapour pressure, primary
      and ultimate biodegradation potential, acute toxicity (LD50) on P. perdix, and
      endocrine disruption potential. From these physicochemical and toxicological
      data, the system of integration of risk with interaction of scores (SIRIS) method
      was used to design scores of risk for pesticides, alone or in mixture. A program,
      written in R (version 3.1.1), called Simulation of Toxicity in Perdix perdix
      (SimToxPP), was designed for estimating the risk of substances, considered alone
      or in mixture, against the grey partridge during breeding. The software tool is
      flexible enough to simulate realistic in situ scenarios. Different examples of
      applications are shown. The advantages and limitations of the approach are
      briefly discussed.

PMID- 29206500
TI  - Molecular property diagnostic suite (MPDS): Development of disease-specific open
      source web portals for drug discovery.
AB  - Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug
      discovery and development platform. MPDS web portals are designed for several
      diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders,
      specifically aimed to evaluate and estimate the drug-likeness of a given
      molecule. MPDS consists of three modules, namely data libraries, data processing,
      and data analysis tools which are configured and interconnected to assist drug
      discovery for specific diseases. The data library module encompasses vast
      information on chemical space, wherein the MPDS compound library comprises 110.31
      million unique molecules generated from public domain databases. Every molecule
      is assigned with a unique ID and card, which provides complete information for
      the molecule. Some of the modules in the MPDS are specific to the diseases, while
      others are non-specific. Importantly, a suitably altered protocol can be
      effectively generated for another disease-specific MPDS web portal by modifying
      some of the modules. Thus, the MPDS suite of web portals shows great promise to
      emerge as disease-specific portals of great value, integrating chemoinformatics,
      bioinformatics, molecular modelling, and structure- and analogue-based drug
      discovery approaches.

PMID- 29206501
TI  - Synthesis and investigation of binding interactions of 1,4-benzoxazine
      derivatives on topoisomerase IV in Acinetobacter baumannii.
AB  - Acinetobacter baumannii has emerged as an important pathogen for nosocomial
      infections having high morbidity and mortality. This pathogen is notorious for
      antimicrobial resistance to many common antimicrobial agents including
      fluoroquinolones, which have both intrinsic and acquired resistance mechanisms.
      Fluoroquinolones targeting the bacterial topoisomerase II (DNA gyrase and Topo
      IV) show potent broad-spectrum antibacterial activity by the stabilization of the
      covalent enzyme-DNA complex. However, their efficacy is now being threatened by
      an increasing prevalence of resistance. Fluoroquinolones cause stepwise mutations
      in DNA gyrase and Topo IV, having alterations of their binding sites.
      Furthermore, the water-Mg+2 bridge, which provides enzyme-fluoroquinolone
      interactions, has a significant role in resistance. In this study, 13 compounds
      were synthesized as 1,4-benzoxazine derivatives which act as bacterial
      topoisomerase II inhibitors and their antibacterial activities were determined
      against multi-drug resistant Acinetobacter strains which have ciprofloxacin (CIP)
      resistant and GyrA mutation. Afterwards we performed docking studies with Topo IV
      (pdb:2XKK) of these compounds to comprehend their binding properties in Discovery
      Studio 3.5. The results of this study show significant conclusions to elucidate
      the resistance mechanism and lead to the design of new antibacterial agents as
      bacterial topoisomerase II inhibitors.

PMID- 29206502
TI  - Synthesis and activity mechanism of some novel 2-substituted benzothiazoles as
      hGSTP1-1 enzyme inhibitors.
AB  - Human GSTP1-1 is one of the most important proteins, which overexpresses in a
      large number of human tumours and is involved in the development of resistance to
      several anticancer drugs. So, it has become an important target in cancer
      treatment. In this study, 12 benzothiazole derivatives were synthesized and
      screened for their in vitro inhibitory activity for hGSTP1-1. Among these
      compounds, two of them (compounds #2 and #5) have been found to be the leads when
      compared with the reference drug etoposide. In order to analyse the structure
      activity relationships (SARs) and to investigate the binding side interactions of
      the observed lead compounds, a HipHop pharmacophore model was generated and the
      molecular docking studies were performed by using CDocker method. In conclusion,
      it is observed that the lead compounds #2 and #5 possessed inhibitory activity on
      the hGSTP1-1 by binding to the H-site as a substrate in which the para position
      of the phenyl ring of the benzamide moiety on the benzothiazole ring is
      important. Substitution at this position with a hydrophobic group that reduces
      the electron density at the phenyl ring is required for the interaction with the
      H side active residue Tyr108.

PMID- 29206503
TI  - Patients can bid farewell to 'Cadillac' healthcare.

PMID- 29206504
TI  - Rural medicine: rocky soil for managed care?

PMID- 29206505
TI  - Managed care can be quality care.

PMID- 29206507
TI  - Will personal freedom survive reform?

PMID- 29206506
TI  - Is old-fashioned patient care obsolete?

PMID- 29206508
TI  - Patients Worry About Rationing And Long Lines.

PMID- 29206510
TI  - Medicine for the masses: what suffers?

PMID- 29206509
TI  - Now, Do Something!

PMID- 29206511
TI  - Change is coming to doctor-patient relationships.

PMID- 29206513
TI  - Rx for healthcare: let patients pay their share.

PMID- 29206512
TI  - The reform-plan maze.

PMID- 29206514
TI  - When bigger isn't better.

PMID- 29206516
TI  - Your hotline to the players in Washington.

PMID- 29206515
TI  - Who will advocate for patients?

PMID- 29206517
TI  - Will reform limit access for rural patients?

PMID- 29206518
TI  - 'We're going to survive' a solo practitioner digs in his heels.

PMID- 29206520
TI  - Government-managed healthcare.
AB  - According to Cato Institute chairman William A. Niskanen, government-mandated
      managed competition will fail to control healthcare costs and will pose a serious
      threat to the quality of American medical care. Mr Niskanen elaborates on this
      viewpoint in the following remarks, which were originally delivered in a speech.

PMID- 29206519
TI  - Proposed changes in malpractice law.
AB  - Most of the healthcare reform plans recently introduced in Congress propose
      changes in medical liability law. Will these changes suffice to stem the rising
      tide of malpractice suits? How will healthcare professionals be affected by the
      legislation? The authors, a physician and an attorney, address these and other
      questions as they analyze the malpractice provisions of five plans and offer
      their own recommendations for reform.

PMID- 29206521
TI  - Does Congress know what YOU think?

PMID- 29206522
TI  - What private-practice doctors can do to contain costs.
AB  - Not all of the costs of private practice, particularly those related to
      government regulation, are within your control. However, there are steps, both
      large and small, that you can take to get fees under control and to eliminate or
      reduce expenditures. Dr Orient suggests a number of these.

PMID- 29206523
TI  - What managed-care doctors can do to contain costs.
AB  - Why does the government need to be involved in cost containment in the healthcare
      industry? Can't physicians improve efficiency and see more patients without
      federal rules, regulations, and limits? Dr Clanton shares some ideas about
      increasing efficiency in managed-care operations, describing ways that physicians
      and administrators can decrease the cost of healthcare delivery.

PMID- 29206524
TI  - How physicians will benefit under Clinton's plan.
AB  - President Clinton's healthcare reform plan will be good for primary care
      physicians, according to Judith Feder, one of the administration's top health
      policy advisers. During a 20-minute phone interview recently, she told
      postgraduate medicine that the goal is to reduce governmental and other kinds of
      hassles for practitioners while holding them accountable for results. Her
      responses to other concerns of physicians follow.

PMID- 29206525
TI  - Making managed care work for you.
AB  - Making a practice cost-effective and profitable does not have to come at the
      expense of quality care. By incorporating managed care into their practices, the
      authors were able to find a successful balance. In this article, they lay out
      tips that would benefit physicians thinking of setting up their own managed-care
      centers as well as those looking to fine-tune or expand their current practices.

PMID- 29206526
TI  - Burning out on solo practice 'you'd like to keep it going but you just can't'.

PMID- 29206527
TI  - Obstructive sleep apnea.
AB  - Preview A group of women are talking about their husbands' sleep habits. Tossing,
      turning, snoring, and falling asleep in the easy chair right after dinner come
      up. Then someone says, "What really bothers me is when he quits breathing."
      Several other spouses agree. What they may not know is that this is sleep apnea,
      which can have serious consequences if left untreated. Drs Chua and Chediak
      discuss risk factors, causes, diagnosis, and treatment of obstructive sleep
      apnea.

PMID- 29206528
TI  - Attention-deficit hyperactivity disorder.
AB  - Preview Children who fidget, chatter incessantly, interrupt, and hop from one
      activity to another may be very tiring to be around. Worse yet, their behavior
      limits their ability to learn and make friends and may have long-term
      consequences for themselves as well as their families. The authors review the
      features of attention-deficit hyperactivity disorder and summarize pharmacologic,
      educational, and behavioral intervention.

PMID- 29206529
TI  - Oral empirical treatment of pneumonia.
AB  - Preview Physicians treating community-acquired pneumonia in adults are faced with
      the challenge of selecting an antimicrobial agent and initiating therapy before a
      precise cause can be identified. Dr Gleckman discusses factors that can help
      identify the most likely pathogens, describes advantages and disadvantages of
      several newer compounds used to treat pneumonia, and outlines an approach to
      empirical therapy that is based on the patient's age and medical history.

PMID- 29206531
TI  - Our own Organizations are Campaigning for a Healthcare Bureaucracy.

PMID- 29206530
TI  - Peripartum complications.
AB  - Preview Complications around the time of delivery remain a serious problem in
      this country. Many women are having children later in life, and medical
      conditions that increase risk may have had time to develop. Drs Ritter and
      deShazo explain the various risk factors as they describe diagnosis and treatment
      of these complications. As they point out, the conditions need to be identified
      and treated immediately, and this task often falls into the hands of primary care
      physicians.

PMID- 29206532
TI  - Lipoproteins and apolipoproteins.
AB  - Preview Plasma contains four major lipoprotein particles: chylomicrons, VLDLs,
      LDLs, and HDLs. How cholesterol is metabolized depends on the particle with which
      it is associated. Thus, treatment for hypercholesterolemia is most effective when
      it is designed to fit the lipoprotein features of a given patient. Dr Kottke
      describes the five common forms of hyperlipoproteinemia and provides specific
      therapeutic approaches for each.

PMID- 29206533
TI  - Dyslipidemias in diabetic patients.
AB  - Preview Coronary artery disease is the most common cause of premature death in
      both men and women with diabetes. Thus, optimal care should address
      atherosclerotic risk factors, which in diabetic patients center on elevated
      triglyceride levels and decreased high-density lipoprotein cholesterol levels. Dr
      Gates discusses when and how to treat dyslipidemias in this special population.

PMID- 29206534
TI  - Gastroesophageal reflux disease.
AB  - Preview President Clinton's hoarseness during the presidential campaign
      represents one of the diverse presentations of gastroesophageal reflux disease.
      Its prevalence is difficult to determine because so many people with mild
      symptoms treat themselves. Dr Robinson describes the manifestations and causes of
      chronic reflux and discusses a multiphasic approach to treatment. Future uses of
      over-the-counter histamine2 blockers (which are still in development) are also
      explored.

PMID- 29206535
TI  - Gout and 'pseudogout'.
AB  - Preview Two crystal compounds-monosodium urate and calcium pyrophosphate
      dihydrate-can accumulate in connective tissue and/or joints and can present
      clinically in several ways. The authors discuss the typical patterns seen with
      each of the arthropathies induced by these crystals, the options available for
      treatment, and, in the case of gout, ways for preventing recurrence. They also
      describe identifying radiographic and microscopic characteristics and provide
      representative illustrations.

PMID- 29206536
TI  - Helicobacter pylori and peptic ulcer disease.
AB  - Preview Eradication of Helicobacter pylori clearly reduces the recurrence rate of
      peptic ulcer disease. Although a preferred treatment regimen has not been
      established, triple-drug therapy that combines antibiotics with bismuth is
      recommended. Dr Fedotin suggests, however, that this treatment only be used in
      selected patients, because it is expensive and may have undesirable side effects.

PMID- 29206537
TI  - Congestive heart failure.

PMID- 29206538
TI  - Hat Trick.

PMID- 29206539
TI  - The facts about fibroids.
AB  - Preview Uterine fibroids develop in more than half of all women and are the most
      common indication for major surgery in women. How do these tumors present, and
      what diagnostic techniques are useful? What are the latest developments in
      medical treatment? When is surgery indicated? Dr Christiansen answers these and
      other questions in this review.

PMID- 29206540
TI  - Thyroid dysfunction in the severely ill and elderly.
AB  - Preview Manifestations of thyroid dysfunction may be totally misleading in
      severely ill and elderly patients, often confounding clinical diagnosis. To
      prevent undue morbidity and mortality in these patients, appropriate selection
      and accurate interpretation of thyroid function tests are crucial. In this
      article, Dr Isley compares the classic signs and symptoms of thyroid disorders
      with those that may appear in elderly patients and in patients severely ill with
      other diseases, and he presents algorithms for diagnosing thyrotoxicosis and
      hypothyroidism.

PMID- 29206541
TI  - Modern management of epilepsy.
AB  - Preview Your new patient has epilepsy. You remember most of what you learned in
      medical school and you've seen a few cases since, but you know that things have
      changed. What are the latest medical regimens and surgical procedures? Which
      drugs are being used now, and what can you expect from them? Dr Wyler, director
      of a center devoted to management of epilepsy, fills in the details in this easy
      to-read article.

PMID- 29206542
TI  - Noninvasive assessment of systolic and diastolic function.
AB  - Preview No one has "just CHF" any longer. The increasing sophistication of
      diagnostic tools has turned a simple diagnosis into a technologic feast. Both
      systolic and diastolic left ventricular function in patients with CHF can now be
      accurately defined by using M-mode, two-dimensional, and Doppler echocardiography
      and radionuclide angiography. Even if your practice does not include these
      testing capabilities, knowing how to interpret the results and knowing the
      diagnostic clues on physical examination enhance your ability to care for any
      type of patient with CHF.

PMID- 29206543
TI  - Invasive testing in congestive heart failure.
AB  - Preview Cardiac catheterization of patients with congestive heart failure (CHF)
      can provide information that may indicate the cause of the CHF, suggest its
      prognosis, or serve as a basis for treatment decisions. Under what circumstances
      do CHF patients require hemodynamic assessment? What are the benefits of contrast
      angiography and coronary arteriography? Why is it important to consider
      endomyocardial biopsy in any patient with CHF who does not have significant
      coronary or valvular disease? Dr Murali addresses these and other questions.

PMID- 29206545
TI  - Snow Jobs.

PMID- 29206546
TI  - Drug dosing in patients with renal insufficiency.
AB  - Preview When drugs are prescribed for patients with renal insufficiency, the
      dosage regimen may need to be altered to prevent toxic accumulation of drugs or
      their metabolites. An increase in the dosing interval is preferred over dose
      reduction for drugs excreted by the kidney. In this article, the authors explain
      how renal impairment interferes with the disposition of drugs and present
      guidelines to reduce drug-induced side effects and improve patient outcomes.

PMID- 29206544
TI  - A Complication of Percutaneous Sclerotherapy for Congenital Pulmonary Airway
      Malformation: Intravascular Injection and Cardiac Necrosis.
AB  - INTRODUCTION: A congenital pulmonary airway malformation (CPAM) type III may
      become large enough to cause hydrops fetalis. In such circumstances, the fetus
      can be treated with open fetal resection, maternal betamethasone administration,
      or percutaneous sclerotherapy. CASE REPORT: A 24 week gestation fetus with a CPAM
      type III was treated by percutaneous sclerotherapy using ethanolamine oleate
      (EO). The EO inadvertently entered the left atrium and ventricle with subsequent
      fetal bradycardia and demise. Autopsy revealed myocardial necrosis. CONCLUSION:
      Percutaneous sclerotherapy has been previously described in the literature for
      the treatment of microcystic CPAMs with secondary hydrops. This is the first
      reported case of an adverse event after fetal sclerotherapy.

PMID- 29206547
TI  - Rheumatoid arthritis.
AB  - Preview Once considered relatively benign, rheumatoid arthritis is now recognized
      as a disabling systemic disease that causes substantial morbidity and mortality.
      Early, aggressive therapy may be critical for altering the course of disease. Drs
      Vikings-son and Graziano describe the causes and clinical course of rheumatoid
      arthritis and discuss diagnostic considerations and prognostic indicators that
      support optimum management.

PMID- 29206548
TI  - Chronic pelvic pain.
AB  - Preview What do complaints of sleeplessness, depression, childhood sexual abuse,
      and dysfunctional family and marital relationships have to do with chronic pelvic
      pain? Maybe a lot, according to the authors' findings in studies of patients at a
      clinic for chronic pain. The authors describe diagnostic clues to watch for
      during history taking, an approach to differential diagnosis (including use of
      the "torso score"), and therapeutic options.

PMID- 29206549
TI  - Chronic bronchitis.
AB  - Preview A number of therapies may be beneficial to patients with chronic
      bronchitis, but quitting smoking is the first and most important step. The
      authors of this article explain why smoking cessation is so essential for
      improvement of symptoms and preservation of pulmonary function. They also discuss
      current pharmacologic approaches to management of chronic bronchitis.

PMID- 29206550
TI  - Headache in elderly patients.
AB  - Preview Although headaches in elderly patients are usually benign, they are
      common and some can be life-threatening. Precise diagnosis is imperative for
      optimum pain management and early detection of underlying organic disorders. Dr
      Ruoff discusses the primary types of benign headache, current diagnostic
      criteria, and appropriate pharmacologic and non-pharmacologic therapies. Organic
      causes of headache are also discussed.

PMID- 29206551
TI  - Hepatocellular carcinoma.
AB  - Preview Although hepatocellular carcinoma is rare in the United States, it is a
      serious disease that will likely increase in incidence with the changing patterns
      of immigration. The vast majority of patients with hepatocellular carcinoma have
      been exposed to hepatitis B or hepatitis C, and all three diseases have the same
      geographic distribution. Thus, a link between the diseases seems indisputable.
      The authors define the populations at risk for hepatocellular carcinoma and
      describe the availability and use of screening methods.

PMID- 29206552
TI  - Chronic bronchitis.
AB  - Preview Wheezing, difficulty in breathing, and coughing that produces thick
      sputum are all symptoms of chronic bronchitis. Differentiating this very common
      disorder from other pulmonary diseases with similar symptoms can be difficult.
      What factors contribute to the disorder? What should be the focus of clinical
      evaluation? In this article, Drs Kronenberg and Griffith answer these and other
      questions relating to evaluation of chronic bronchitis.

PMID- 29206553
TI  - Development of Imminent Mortality Predictor for Advanced Cancer (IMPAC), a Tool
      to Predict Short-Term Mortality in Hospitalized Patients With Advanced Cancer.
AB  - PURPOSE: End-of-life care for patients with advanced cancer is aggressive and
      costly. Oncologists inconsistently estimate life expectancy and address goals of
      care. Currently available prognostication tools are based on subjective clinical
      assessment. An objective prognostic tool could help oncologists and patients
      decide on a realistic plan for end-of-life care. We developed a predictive model
      (Imminent Mortality Predictor in Advanced Cancer [IMPAC]) for short-term
      mortality in hospitalized patients with advanced cancer. METHODS: Electronic
      health record data from 669 patients with advanced cancer who were discharged
      from Yale Cancer Center/Smilow Cancer Hospital were extracted. Statistical
      learning techniques were used to develop a tool to estimate survival
      probabilities. Patients were randomly split into training (70%) and validation
      (30%) sets 20 times. We tested the predictive properties of IMPAC for mortality
      at 30, 60, 90, and 180 days past the day of admission. RESULTS: For mortality
      within 90 days at a 40% sensitivity level, IMPAC has close to 60% positive
      predictive value. Patients estimated to have a greater than 50% chance of death
      within 90 days had a median survival time of 47 days. Patients estimated to have
      a less than 50% chance of death had a median survival of 290 days. Area under the
      receiver operating characteristic curve for IMPAC averaged greater than .70 for
      all time horizons tested. Estimated potential cost savings per patient was
      $15,413 (95% CI, $9,162 to $21,665) in 2014 constant dollars. CONCLUSION: IMPAC,
      a novel prognostic tool, can generate life expectancy probabilities in real time
      and support oncologists in counseling patients about end-of-life care.
      Potentially avoidable costs are significant.

PMID- 29206554
TI  - Front-Line Treatment Options for Chronic-Phase Chronic Myeloid Leukemia.
AB  - The Oncology Grand Rounds series is designed to place original reports published
      in the Journal into clinical context. A case presentation is followed by a
      description of diagnostic and management challenges, a review of the relevant
      literature, and a summary of the authors' suggested management approaches. The
      goal of this series is to help readers better understand how to apply the results
      of key studies, including those published in Journal of Clinical Oncology, to
      patients seen in their own clinical practice. A 40-year-old woman with a past
      medical history of hypertension and occasional premature ventricular contractions
      was found on routine blood work in June 2011 to have mild thrombocytosis, with a
      platelet count of 405,000. In November 2011, repeat analysis revealed a platelet
      count of 433,000, and by February 2012 her platelet count was 509,000. She had no
      evidence of leukocytosis or anemia and no symptoms of early satiety, night
      sweats, pruritus, or erythromelalgia. She was referred to a hematologist for
      evaluation of persistent isolated thrombocytosis in March 2012. Her spleen was
      not palpable, and a quantitative polymerase chain reaction (PCR) test for
      JAK2/V617F was negative. A bone marrow biopsy and aspiration revealed a mildly
      hypercellular marrow (70% to 80% cellularity), with an elevated myeloid:erythroid
      ratio of 5:1, increased megakaryocytes including micromegakaryocytes in the
      absence of increased blasts. Cytogenetic analysis revealed the presence of the
      Philadelphia chromosome translocation in 17 out of 20 metaphases. The remaining
      three metaphases were normal karyotype. Quantitative PCR for BCR-ABL1 yielded a
      value of 29.6% on the International Scale.

PMID- 29206555
TI  - A Connectedness Primer for Healthcare Providers: Adolescents/Young Adult Cancer
      Survivors' Perspectives on Behaviors That Foster Connectedness During Cancer
      Treatment and the Resulting Positive Outcomes.
AB  - PURPOSE: Many healthcare providers (HCPs) struggle to communicate and connect
      with adolescents and young adults (AYA) with cancer that hinders their ability to
      adequately assess and address the psychosocial needs of AYA. The purpose of this
      article is to describe the key behaviors of HCPs AYA perceive as essential to
      fostering connectedness with them and the outcomes AYA experience from such
      connectedness. METHODS: The sample for this empirical phenomenological study was
      nine AYA cancer survivors (aged 20-23 years) who were diagnosed in adolescence.
      In-person individual interviews were conducted using a broad, data-generating
      question and analyzed using an adapted Colaizzi's method. RESULTS: The key
      behaviors of HCPs AYA perceive as essential to fostering connectedness include
      (1) exhibiting characteristics of knowing how to connect; (2) being watchful and
      attentive to AYA needs; (3) displaying a willingness to foster the relationship;
      (4) using humor; and (5) conveying respect, support, and caring. Outcomes of
      connectedness for AYA include a sense of being cared about, understood, and
      respected as unique individuals. In addition, AYA experience a sense of
      confidence/comfort in expressing themselves to HCPs, anticipation of interacting
      with HCPs in the future, a sense of gratitude for HCPs, and enhanced well-being.
      CONCLUSION: Findings highlight the specific behaviors HCPs can use to foster
      connectedness with AYA and the outcomes AYA experience from connectedness.
      Improving HCPs' ability to connect with AYA and maintain connectedness is
      essential to identifying and addressing the psychosocial needs of AYA. AYA-HCP
      connectedness may help reduce the psychosocial distress AYA experience during and
      after treatment.

PMID- 29206557
TI  - Selection Bias in Colorectal Surgery in a Non-Tertiary Hospital: Laparoscopic
      Versus Open Surgery.
AB  - INTRODUCTION: Laparoscopy is used increasingly to treat malignant and benign
      colorectal surgical diseases. However, this practice is still not offered to all
      patients. Many barriers halt the widespread use of laparoscopic colorectal
      surgery. Both surgeon's and patient's factors contribute to limit a wider use of
      laparoscopy in colorectal surgery. MATERIALS AND METHODS: We retrospectively
      analyzed 408 consecutive colorectal resections in a 4-year period, to find out if
      a selection bias exists in using laparotomy or laparoscopy for colorectal
      surgical diseases, and which factors are associated with a poor use of
      laparoscopy or to a preferred laparotomy. RESULTS: In our practice, advanced
      disease, American Society of Anesthesiologist class III and IV, and emergency
      status are all patient-related factors associated with laparotomy. Surgeon's age
      more than 52 years and lack of laparoscopic training are surgeon-related factors
      that negatively affect the chance of being operated on with the laparoscopic
      technique. CONCLUSIONS: An extensive laparoscopic colorectal training and a
      supporting environment, especially during the night shift, are needed to
      facilitate the use of laparoscopy in colorectal surgery avoiding a bias in
      selecting surgical candidates to one technique or another.

PMID- 29206556
TI  - Intravitreal, Subretinal, and Suprachoroidal Injections: Evolution of
      Microneedles for Drug Delivery.
AB  - Even though the very thought of an injection into the eye may be frightening, an
      estimated 6 million intravitreal (IVT) injections were made in the USA during
      2016. With the introduction of new therapeutic agents, this number is expected to
      increase. In addition, drug products that are injectable in ocular compartments
      other than the vitreous humor are expected to enter the back of the eye market in
      the not so distant future. Besides the IVT route, some of the most actively
      investigated routes of invasive administration to the eye include periocular,
      subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the
      driving force behind new injectable drug product development for the eye, safety
      is also being improved with time. In the case of IVT injections, the procedural
      guidelines have evolved over the years to improve patient comfort and reduce
      injection-related injury and infection. Similar advances are anticipated for
      other routes of administration of injectable products to the eye. In addition to
      procedural improvements, the design of needles, particularly those with smaller
      diameters, length, and controlled bevel angles are expected to improve overall
      safety and acceptance of injected ophthalmic drug products. A key development in
      this area is the introduction of microneedles of a length less than a millimeter
      that can target the SC space. In the future, needles with smaller diameters and
      lengths, potentially approaching nanodimensions, are expected to revolutionize
      ophthalmic disease management.

PMID- 29206558
TI  - Toxic shock syndrome.
AB  - Preview Toxic shock syndrome is no longer a disease that affects only young,
      menstruating women. Staphylococcal toxic shock syndrome has been diagnosed with
      increasing frequency in children, men, and older women, and a streptococcal
      syndrome affecting both sexes and all age-groups has been identified. The variant
      presentations of these infections can make diagnosis difficult. Dr Strausbaugh
      describes the features of both the staphylococcal and the streptococcal forms of
      toxic shock syndrome and offers tips for rapid recognition.

PMID- 29206559
TI  - Primary sclerosing cholangitis and primary biliary cirrhosis.
AB  - Preview Although primary sclerosing cholangitis occurs most often in middle-aged
      or younger men and primary biliary cirrhosis in middle-aged or older women, the
      diseases have some traits in common-unfortunate ones. In both diseases, the cause
      is unknown, and liver transplantation is the only known effective therapy for
      advanced cases. Dr Fennerty discusses trials of medical treatments used in an
      attempt to arrest progression of these diseases and summarizes the outcomes.

PMID- 29206560
TI  - Prevention of myocardial reinfarction.
AB  - Preview The number of cardiac drugs is growing every day, and their indications
      are changing as more is learned about each one. Choosing the appropriate drug for
      each patient is made difficult by these complexities, especially when a patient
      has already had a heart attack. The authors review the latest trials of the major
      classes of cardiac drugs and give recommendations that will help physicians make
      a reasonable choice of drug therapy for each patient.

PMID- 29206561
TI  - Gallstones.
AB  - Preview Gallstones, already estimated to occur in 1 of every 10 Americans, may be
      even more common than that, since many stones are asymptomatic and discovered
      only incidentally. In an effort to avoid the expense of surgery and the recovery
      period afterward, investigators have developed pharmacologic, radiographic, and
      other nonsurgical treatment methods, which continue to be refined. Dr Jaffe
      summarizes these alternatives, patient selection, success rates, and
      posttreatment recurrence.

PMID- 29206562
TI  - Biliary obstruction.
AB  - Preview In a state-of-the art medical center, stones in the bile duct can be
      fragmented with stone-crushing baskets or electro- hydraulic or laser probes
      passed through an endoscope. Or they can be snared in a basket catheter inserted
      through a T-tube tract and guided by fluoroscopy. Expanding metallic mesh stents
      are being developed for use in biliary strictures and may have prolonged patency.
      However, as Dr Hixson emphasizes, the success of these and the other techniques
      described in this article depends on the skill and experience of available
      endoscopists and interventional radiologists.

PMID- 29206563
TI  - Benign prostatic hyperplasia.
AB  - Preview Management of benign prostatic hyperplasia (BPH) is no longer the cut-and
      dried topic that it once was. In this article, Dr Moul presents an update on new
      medical therapies for mild and moderate cases of BPH and on surgical
      interventions (some experimental) for more advanced cases. He predicts that
      intensive research during the next decade will lead to more insight into the most
      effective therapies for this condition.

PMID- 29206564
TI  - Advance Care Planning in an Accountable Care Organization Is Associated with
      Increased Advanced Directive Documentation and Decreased Costs.
AB  - BACKGROUND: Advance care planning (ACP) documents patient wishes and increases
      awareness of palliative care options. OBJECTIVE: To study the association of
      outpatient ACP with advanced directive documentation, utilization, and costs of
      care. DESIGN: This was a case-control study of cases with ACP who died matched
      1:1 with controls. We used 12 months of data pre-ACP/prematch and predeath. We
      compared rates of documentation with logit model regression and conducted a
      difference-in-difference analysis using generalized linear models for utilization
      and costs. SETTING/SUBJECTS: Medicare beneficiaries attributed to a large rural
      suburban-small metro multisite accountable care organization from January 2013 to
      April 2016, with cross reference to ACP facilitator logs to find cases.
      MEASUREMENTS: The presence of advance directive forms was verified by chart
      review. Cost analysis included all utilization and costs billed to Medicare.
      RESULTS: We matched 325 cases and 325 controls (51.1% female and 48.9% male, mean
      age 81). 320/325 (98.5%) ACP versus 243/325 (74.8%) of controls had a Healthcare
      Power of Attorney (odds ratio [OR] 21.6, 95% CI 8.6-54.1) and 172/325(52.9%) ACP
      versus 145/325 (44.6%) controls had Practitioner Orders for Life Sustaining
      Treatment (OR 1.40, 95% CI 1.02-1.90) post-ACP/postmatch. Adjusted results showed
      ACP cases had fewer inpatient admissions (-0.37 admissions, 95% CI -0.66 to 
      0.08), and inpatient days (-3.66 days, 95% CI -6.23 to -1.09), with no
      differences in hospice, hospice days, skilled nursing facility use, home health
      use, 30-day readmissions, or emergency department visits. Adjusted costs were
      $9,500 lower in the ACP group (95% CI -$16,207 to -$2,793). CONCLUSIONS: ACP
      increases documentation and was associated with a reduction in overall costs
      driven primarily by a reduction in inpatient utilization. Our data set was
      limited by small numbers of minorities and cancer patients.

PMID- 29206565
TI  - Absorption, distribution, metabolism, and excretion of mTOR kinase inhibitor CC
      223 in rats, dogs, and humans.
AB  - 1. The absorption, distribution, metabolism, and excretion of CC-223 were studied
      following a single oral dose of [14C]CC-223 to rats (3 mg/kg; 90 MUCi/kg), dogs
      (1.5 mg/kg; 10 MUCi/kg), and healthy volunteers (20 mg; 200 nCi). 2. CC-223
      derived radioactivity was widely distributed in rats. Excretion of radioactivity
      was rapid and nearly complete from rats (87%), dogs (78%), and humans (97%).
      Feces was the major excretion pathway for rats (67%) and dogs (70%), whereas
      urine (57.6%) was the major elimination route for humans. Urine and bile each
      contained approximately 20% administered radioactivity in rats, whereas bile
      (20%) played a more important role than urine (<10%) in the excretion of absorbed
      radioactivity in dogs. Based on excretion data, CC-223 had good absorption, with
      greater than 56%, 29%, and 57% of the oral dose absorbed in rats, dogs, and
      humans, respectively. 3. CC-223 was the prominent radioactive component in
      circulation of rats (>71% of the exposure to total radioactivity) and dogs
      (>=45.5%), whereas M1 (76.5%) was the predominant circulating metabolite in
      humans. M1 and M1-derived metabolites accounted for >66% of human dose. CC-223
      was extensively metabolized in rats, dogs, and humans through glucuronidation, O
      demethylation, oxidation, and combinations of these pathways.

PMID- 29206566
TI  - Preferences and Inhalation Techniques for Inhaler Devices Used by Patients with
      Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Inhaler technique and patient preferences are often overlooked when
      selecting maintenance treatments for patients with chronic obstructive pulmonary
      disease (COPD), but are important issues in ensuring drug efficacy and patient
      adherence. Few data on these issues are available for new inhalation devices.
      OBJECTIVES: To evaluate the inhalation techniques for the HandiHaler(r),
      Breezhaler(r), Genuair(r), and Respimat(r) inhalation devices, and patient
      preferences for the three latter inhalers that were recently developed. METHODS:
      A prospective two-center cross-sectional study of COPD patients was conducted.
      The patients were required to be current HandiHaler users who had not previously
      used the new inhalers (Breezhaler, Genuair, Respimat). The patients were given
      the new devices and asked to identify the one they preferred before and after
      using the inhaler. Each patient tried the HandiHaler and two devices out of the
      three new inhalers: one preferred by the patient and one imposed by the
      investigator. Their inhalation technique was evaluated using an assessment
      checklist. A logistic regression model was used to determine which device was
      used with the fewest errors. RESULTS: Of the 98 patients who completed the study,
      57.1% (95% CI: 47.4-66.9) had an adequate HandiHaler technique. There was no
      difference between the proportions of patients with an adequate Breezhaler and
      Genuair inhalation technique (aOR 1.08, 95% CI: 0.51-2.30), but 62% fewer
      patients using Respimat had an adequate technique than those using Genuair (aOR
      for adequate technique 0.38, 95% CI: 0.18-0.82). There were no significant
      differences in the initial patient preferences for the three new inhalers, and no
      association between the patient's preference and an adequate inhaler technique.
      CONCLUSION: Inhalation techniques were suboptimal and varied between inhalers.
      The arrival of new inhalers is an opportunity to reassess patient techniques and
      preferences. Further studies should also explore the association between the
      inhaler preferences and treatment adherence of patients.

PMID- 29206567
TI  - Comparison of Robotic Pyeloplasty and Standard Laparoscopic Pyeloplasty in
      Infants: A Bi-Institutional Study.
AB  - PURPOSE: To compare outcomes between robotic pyeloplasty (RP) and standard
      laparoscopic pyeloplasty (LP) in the infant population for the treatment of
      ureteropelvic junction (UPJ) obstruction. MATERIALS AND METHODS: We performed a
      retrospective cohort study of all children under 1 year of age who underwent RP
      or LP at two different medical centers between October 2009 and February 2016.
      Patient demographics, perioperative data, complications, and results were
      reviewed. RESULTS: Thirteen patients underwent standard LP, and 21 patients
      underwent RP during the study period. Median age and median weight at time of
      operation for the whole cohort were 6.1 months and 7.9 kg. Surgery success rates
      were similar with 95% and 92% in RP and LP, respectively. There was no
      statistically significant difference in operating time between the 2 groups, with
      a median time of 156 minutes in RP (range 125-249) and 192 minutes (range 98-229)
      in standard LP (P = .35). Median length of hospital stay was significantly
      shorter in the robotic group with a median stay of 1 day (range 1-3) and 7 days
      (range 7-12) in the standard LP group.(P < .0001) Drains or nephrostomy tubes
      were used more often in the laparoscopic group (100%, 13/13) as opposed to RP
      (9.5%, 2/21, P < .0001) There was a comparable complication rate between the 2
      groups, 30.8% for LP and 23.8% for RP (P = .65). CONCLUSIONS: The minimally
      invasive dismembered pyeloplasty is safe and effective in the infant population
      and produces high success rates. The results, complication rates, and operative
      time were comparable between the two surgical methods while the standard LP
      demonstrated longer hospital stay. Both the robotic approach and the LP can be
      successfully utilized for the benefit of infants with UPJ obstruction.

PMID- 29206568
TI  - In Utero Exposure to Opioids: An Observational Study of Mothers Involved in the
      Child Welfare System.
AB  - BACKGROUND: Women are underrepresented in the current substance abuse research;
      however, women are a particularly vulnerable population when it comes to opioid
      use and abuse. Pregnant women are even more so, because of the potential that
      exists for in utero exposure (IUE) to substances. OBJECTIVES: To identify trends
      in IUE to opioids in order to ensure that resources are allocated effectively to
      address the current opioid epidemic and to assist the populations most affected
      by it. METHODS: This study draws on 15 years' worth of clinical assessment data
      collected from 3598 child welfare-involved mothers to assess for trends in IUE to
      substances over time. Data from the last 5 year period (N = 852) are then
      analyzed to identify recent demographic correlates associated with IUE to opioid
      substances. RESULTS: A substantial increase in the rates of IUE to opioids over
      the past 15 years is observed among child welfare-involved mothers. Moreover, we
      find that race is a significant correlate of IUE to opioids. CONCLUSION: Study
      findings are consistent with other recent research that demonstrates racial
      differences in the populations that are most affected by the opioid epidemic;
      however, more research is needed to determine how these racial differences in
      rates of IUE to opioids affect child welfare outcomes.

PMID- 29206569
TI  - Application of Miniature Heart Rate Data Loggers for Use in Large Free-Moving
      Decapod Crustaceans: Method Development and Validation.
AB  - Cardiovascular responses of decapod crustaceans to environmental challenges have
      received extensive attention. However, nearly all of these studies have been
      restricted to lab-based experiments; here we describe a methodology that will
      enable measurement of heart rate (HR) in free-moving decapods in the field. Data
      storage tag heart rate and temperature loggers (DST micro-HRT; Star-Oddi) were
      used to record electrocardiograms (ECG) and HR in large decapod crustaceans.
      These loggers were originally designed for use in vertebrates and must be
      surgically implanted in the body cavity near the heart in order to function. We
      adapted these loggers for external use in large decapod crustaceans. The method
      involved abrading the carapace directly above the heart and placing the
      electrodes of the logger directly on top of the dermal tissue. The logger was
      then secured in place with periphery wax. This method negated some of the more
      intricate operations used for vertebrates. The rapid setup time of approximately
      5 min suggested that animals could be easily instrumented in the field and
      without the use of anesthetic. The logger was calibrated by simultaneously
      measuring the HR changes of a West Indian spider crab Mithrax spinosissimus with
      a pulsed-Doppler flowmeter. The data gathered with the two methods showed a tight
      correlation during an increase in temperature. The loggers were also successfully
      implanted in a variety of other large species of aquatic and terrestrial
      decapods. The data obtained showed that the method works in a broad range of
      species, under different experimental conditions. In each case, the loggers
      comprised less than 1% of the body mass and would be suitable for use in animals
      >300 g. All animals survived the attachment procedures and were feeding and
      active after removal of the loggers. Nearly all previous cardiac measurements on
      decapods have been carried out in controlled laboratory settings. The use of
      these loggers will make significant advances in measuring HR in unrestrained,
      undisturbed animals in their natural environment during extended periods of time
      and has the potential to lead to novel findings.

PMID- 29206570
TI  - Understanding Suicidal Ideation in Latino/a Adolescents Living in Puerto Rico.
AB  - : Puerto Rican adolescents, as well as other Latinos/as, have been identified at
      higher risk for suicidal ideation and attempts compared to other ethnic groups.
      However, research designed to better understand suicidality among Puerto Rican
      adolescents is rare. OBJECTIVE: A socio-cognitive vulnerability model of suicidal
      ideation was tested in adolescents living in Puerto Rico. METHOD: Multiple group
      path analyses were performed to assess the effect of self-reported socio
      environmental and vulnerability factors on suicidal ideation, by sex, in 233
      students from the metropolitan area of San Juan, Puerto Rico. RESULTS: Overall,
      the model explained a large amount of the variance in suicidal ideation (r2 = .59
      for females and r2 = .48 for males). Depressive symptoms had the strongest total
      effect on suicidal ideation for both sexes (r = .69 for females and r = .53 for
      males) and negative life events were the most salient socio-environmental factor.
      Hopelessness had a direct effect on suicidal ideation for males only.
      Externalizing behaviors had a direct effect on suicidal ideation for both males
      and females, but it was particularly strong for females. CONCLUSION: Results
      support the mediating role of vulnerability factors and the differential
      importance of socio-environmental and vulnerability factors in understanding
      suicidal ideation among Puerto Rican adolescents. The relevance of exploring
      different developmental paths to suicidal ideation, separately by sex, is
      discussed.

PMID- 29206571
TI  - Predicting Ambivalence: When Same-Sex Sex Is Only "Sometimes Wrong".
AB  - Despite Americans' growing acceptance of LGBTQ people and their sexual behaviors
      over the past 40 years, approximately 10% of the population consistently
      expresses conflicted feelings, reporting that same-sex sex is only sometimes
      wrong. This research employs a theory of socially structured ambivalence to
      examine how individuals with ambivalence toward the morality of same-sex sex
      differ from those with strong moral stances. Using multinomial regression
      analysis of General Social Survey data, we find that socio-structural conflicts
      e.g. simultaneous membership in institutions with conflicting normative messages
      are predictive of ambivalent attitudes, and the presence of these structured
      conflicts appears to have a cumulative effect. These findings provide evidence of
      the predictive power of socially structured conflicts in producing ambivalent
      attitudes and expand the existing literature on ambivalence and attitudes about
      same-sex relations. We propose that scholars conceptualize ambivalence as a
      distinctly socio-structural and relational construct that may help to signal
      fertile ground for social change.

PMID- 29206572
TI  - Non-Monosex Research Publication in U.S.-Based Social Work Journals Between 2008
      2016.
AB  - An estimated 4% of men and 9% of women identify as non-monosex, a term for sexual
      identities outside of the heterosexual/homosexual binary, such as bisexual,
      pansexual, polysexual, and asexual. In addition to experiences of oppression
      shared with all sexual minorities, non-monosex-identifying persons face
      additional issues of monosex bias in their personal lives, in mass media, and in
      research. Despite social work's commitment to issues of social justice and
      inclusion, prior reviews of the literature have indicated a gap in research on
      non-monosex-identifying persons, which can lead to inappropriate clinical
      practices and continued stigmatization. The authors of this article examined the
      state of social work literature on non-monosex-identifying persons through a
      systematic review and content analysis of primary-study data-based publications
      from 2008 to 2016 in 24 social work journals based in the United States. Only
      four articles were found that met the inclusion criteria, and while 31% of the
      357 total study participants identified as non-monosex, a content analysis showed
      subtle forms of monosex bias in the reporting of study results, such as
      collapsing of gay/lesbian participants with non-monosex participants and the use
      of marginalizing language. Implications and suggestions for future social work
      researchers are discussed.

PMID- 29206573
TI  - Associations between Health Literacy, Cancer-Related Knowledge, and Preventive
      Health Behaviors in Community-Dwelling Korean Adults.
AB  - This cross-sectional study aimed to examine the association between health
      literacy, cancer-related knowledge, and preventive health behaviors among
      community-dwelling adults in Korea. Data were collected from 542 adults aged >=
      18 years living in five big provinces in Korea (Seoul, Gyeonggi-do, Gyeongsang
      do, Chungcheong-do, and Gangwon-do). Socio-demographic and health-related
      characteristics were determined using structured questionnaires. Health literacy,
      cancer-related knowledge, and engagement in preventive health behaviors were
      measured using validated instruments. These three variables differed according to
      socio-demographic and health-related characteristics, such as education, sex,
      age, and marital status. In the hierarchical regression analysis, health literacy
      (beta = 0.26, p < .001) and cancer-related knowledge (beta = 0.21, p < .001) were
      significant predictors of preventive health behavior after adjusting for
      confounding variables. Cancer-related knowledge partially mediated the effect of
      health literacy on preventive health behaviors. Health literacy can play a key
      role in cancer prevention. It is important for healthcare providers to know how
      to deliver cancer-related knowledge and how to help people with low health
      literacy to engage in preventive health behaviors, using a variety of health
      information resources. Further research is needed to develop the instruments to
      assess comprehension of spoken and written health messages for cancer prevention
      and screening.

PMID- 29206574
TI  - The Role of Cultural and Family Values on Social Connectedness and Loneliness
      among Ethnic Minority Elders.
AB  - OBJECTIVES: Ethnic minority elders have high levels of social isolation and
      loneliness. Assumptions about the family providing enough social support exist in
      the literature, contradicting ethnic minority elders' reported levels of
      isolation and loneliness. While structural barriers influence feelings of
      isolation and loneliness, limited information exists about the role of cultural
      factors such as acculturation and family values. Accordingly, this study
      investigated the roles of acculturation and family values on loneliness and
      social isolation among ethnic minority elders. METHODS: Ethnic minority elders (N
      = 123) completed a questionnaire that assessed their social connectedness,
      measured by social network and levels of loneliness, and structural factors such
      as income. Additionally, cultural and family values were assessed by
      acculturation and the 'family as referents' dimension of familism, which refers
      to the belief that family members' behaviour should meet with familial
      expectations. RESULTS: Statistical analysis using hierarchical regression
      indicated that 'family as referents' and acculturation predicted loneliness, but
      not social network. CONCLUSIONS: This study raises the importance of considering
      cultural values when investigating predictors of loneliness among ethnic minority
      elders. CLINICAL IMPLICATIONS: Findings highlight the importance of addressing
      familial expectations in programs aimed at alleviating loneliness among ethnic
      minority elders.

PMID- 29206575
TI  - Gun attitudes on campus: United and divided by safety needs.
AB  - All people share a need for safety. Yet people's pursuit of safety can conflict
      when it comes to guns, with some people perceiving guns as a means to safety and
      others perceiving guns as a threat to safety. We examined this conflict on a U.S.
      college campus that prohibits guns. We distinguished between people (N = 11,390)
      who (1) own a gun for protection, (2) own a gun exclusively for reasons other
      than protection (e.g., collecting, sports), and (3) do not own a gun. Protection
      owners felt less safe on campus and supported allowing guns on campus. They also
      reported that they and others would feel safer and that gun violence would
      decrease if they carried a gun on campus. Non-owners and non-protection owners
      felt the reverse. The findings suggest that protection concerns, rather than gun
      ownership per se, account for diverging perceptions and attitudes about guns and
      gun control.

PMID- 29206576
TI  - A Review of the Literature on LGBTQ Adults Who Experience Homelessness.
AB  - Little is known about lesbian, gay, bisexual, transgender, and queer (LGBTQ)
      adults who experience homelessness. The current review critically analyzes the
      scant literature on LGBTQ adults who experience homelessness, with a particular
      focus on: (1) pathways into homelessness; (2) support needs; (3) targeted
      programming; and (4) exits out of homelessness. A total of 143 articles were
      identified, and 16 articles met the criteria of appropriate age range, article
      quality, and relevance of topic. Results from this review demonstrate that
      homeless LGBTQ adults have unique physical and mental health challenges, largely
      concerning HIV and substance use. Transgender and gender non-conforming adults
      who experience homelessness encounter several challenges in the homelessness
      system, particularly in regard to safety and gender-affirming supports.
      Recommendations focus on practical implications for support and suggestions for
      future research.

PMID- 29206577
TI  - Increased Reporting of Exclusionary Diagnoses Inflate Apparent Reductions in Long
      Stay Antipsychotic Prescribing.
AB  - OBJECTIVE: Over the two years following the 2012 introduction of CMS's National
      Partnership, combined rates of schizophrenia, Tourette's, and Huntington's in US
      long-stay residents increased 12%. We evaluated trends in reporting of these
      diagnoses for the subgroup of long-stay residents on antipsychotics. METHODS:
      Retrospective analysis of Virginia Medicaid claims identified annual utilization
      rates of psychiatric diagnoses for long-stay seniors on antipsychotics. Chi
      square analysis compared rates for the year before March, 2012 with the same 12
      month period 1 year later. A 5-year pre-existing baseline rate was also obtained.
      RESULTS: Diagnosis rates for 2011 were unchanged from baseline. Comparing 2011
      with 2013, diagnoses rates for schizophrenia, Tourette's, and Huntington's
      combined increased 40% (p < .0001), primarily because schizophrenia reporting
      nearly doubled (p < .0001). CONCLUSIONS: For long-stay seniors on antipsychotics,
      reporting of schizophrenia, Tourette's, and Huntington's began increasing in 2012
      and at almost triple the rate CMS described for the general long-stay population.
      The increased reporting of these diagnoses described by CMS since 2012 appears to
      be new and concentrated in residents on antipsychotics Clinical Implications:
      Since antipsychotics prescribed for schizophrenia, Tourette's, and Huntington's
      are excluded from quality-measure auditing, apparent reductions in inappropriate
      long-stay antipsychotic use since the National Partnership may be exaggerated.

PMID- 29206579
TI  - Peripheral neuropathy.
AB  - Preview Peripheral neuropathy affects about one in five older persons, yet it is
      often not recognized as a cause of falls. Why do patients with peripheral
      neuropathy fall? The authors, who have studied this subject extensively, describe
      specific impairments, explain simple clinical techniques to identify functionally
      significant nerve dysfunction, and suggest ways to help patients prevent further
      falls.

PMID- 29206578
TI  - Wellness in Sickness and Health (The W.I.S.H. Project): Advance Care Planning
      Preferences and Experiences Among Elderly Latino Patients.
AB  - OBJECTIVE: To assess advance care planning (ACP) preferences, experiences, and
      comfort in discussing end-of-life (EOL) care among elderly Latinos. METHODS:
      Patients aged 60 and older from the Los Angeles County and University of Southern
      California (LAC+USC) Medical Center Geriatrics Clinic (n = 41) participated in
      this intervention. Trained staff conducted ACP counseling with participants in
      their preferred language, which included: (a) pre-counseling survey about
      demographics and EOL care attitudes, (b) discussion of ACP and optional
      completion of an advance directive (AD), and (c) post-session survey. RESULTS:
      Patients were primarily Spanish speaking with an average of 2.7 chronic medical
      conditions. Most had not previously documented (95%) or discussed (76%) EOL
      wishes. Most were unaware they had control over their EOL treatment (61%), but
      valued learning about EOL options (83%). Post-counseling, 85% reported comfort
      discussing EOL goals compared to 66% pre-session, and 88% elected to complete an
      AD. Nearly half of patients reported a desire to discuss EOL wishes sooner.
      CONCLUSIONS: Elderly Latino patients are interested in ACP, given individualized,
      culturally competent counseling in their preferred language. CLINICAL
      IMPLICATIONS: Patients should be offered the opportunity to discuss and document
      EOL wishes at all primary care appointments, regardless of health status.
      Counseling should be completed in the patient's preferred language, using
      culturally competent materials, and with family members present if this is the
      patient's preference. Cultural-competency training for providers could enhance
      the impact of EOL discussions and improve ACP completion rates for Latino
      patients.

PMID- 29206580
TI  - Diabetic ketoacidosis and hyperosmolar nonketotic state.
AB  - Preview Severe metabolic complications of diabetes mellitus are a common cause of
      morbidity and death in both type I and type II disease. The distinctions between
      diabetic ketoacidosis and hyperosmolar nonketotic state are clearly defined, and
      accurate recognition is important for proper treatment. This article focuses on
      the practical aspects of evaluation and management of these serious diabetic
      complications in adults.

PMID- 29206581
TI  - New developments in acute anticoagulation therapy.
AB  - Preview Heparin has been in use for more than 40 years and is still an important
      agent for inhibiting plasma- and surface-bound thrombin. However, modifications
      have produced low-molecular-weight heparin, which has better bioavailability and
      perhaps other advantages over traditional heparin. Another direction of research
      in anticoagulation therapy has been toward new antithrombin- independent agents.
      Dr Carter describes the present status of studies on heparin and its derivatives,
      direct thrombin inhibitors, and ancrod, a component of snake venom.

PMID- 29206582
TI  - Bumps on the entrance ramp to the information highway.

PMID- 29206583
TI  - Noninvasive positive pressure ventilation.
AB  - Preview In most cases of acute respiratory failure, mechanical ventilation and
      endotracheal intubation are the preferred treatment. However, a noninvasive
      approach is proving valuable in selected patients and has some advantages over
      standard mechanical ventilation. How are patients selected for this therapy? What
      are its risks and benefits? The authors discuss the usefulness and potential role
      of this important new technique.

PMID- 29206584
TI  - Opportunistic fungal infections in patients with HIV disease.
AB  - Preview The increasing number of patients surviving with advanced HIV infection
      presents new challenges to physicians who care for them. As a patient's CD4+ T
      lymphocyte count declines, susceptibility to opportunistic fungal infections
      increases. In this article, Dr Kirchner discusses two commonly encountered
      pathogens, Cryptococcus neoformans and Histoplasma capsulatum.

PMID- 29206585
TI  - The Shifting Healthcare Marketplace.

PMID- 29206586
TI  - Relief of suffering.
AB  - Preview The relief of human suffering has been a sacred duty of physicians for
      thousands of years. Today's focus in medical education, however, is largely
      confined to the diagnosis and treatment of disease. Yet, without a true
      understanding and appreciation of the nature of human suffering, sophisticated
      interventions run the risk of increasing the distress they were meant to
      alleviate. By combining the art and science of medicine, physicians can often
      provide tremendous comfort and relief to patients. Dr O'Brien offers some useful
      suggestions for achieving this goal.

PMID- 29206587
TI  - Common disorders of pigmentation.
AB  - Preview A woman noticing a small patch of pale skin may comment, "My mother used
      to have the same thing." Or a father seeing a milky-brown lesion on his newborn
      may receive the explanation, "It'll go away on its own." Pigmentation
      imperfections are common. Usually they are benign and cause little distress.
      However, some disorders can be disfiguring and some flag possible systemic
      disease. Dr Hacker describes the presentation of a variety of disorders, provides
      illustrations of several, and summarizes therapeutic approaches to those that
      respond to treatment.

PMID- 29206588
TI  - The anti-phospholipid syndrome.
AB  - Preview Antiphospholipid antibodies may be found in a variety of clinical
      situations, including in the absence of systemic disease. Certainly, for cost
      effective healthcare, physicians should not spend resources evaluating otherwise
      healthy people. However, when features of the antiphospholipid syndrome (APS) are
      also present, serious venous or arterial thrombosis or recurrent spontaneous
      abortion may ensue. The authors present a practical overview of the antibodies
      and how to uncover and manage APS.

PMID- 29206589
TI  - Oral anticoagulant therapy.
AB  - Preview The overall prescription of oral anticoagulants has steadily increased as
      important randomized clinical trials have clarified various indications for
      therapy. However, a number of practical matters related to initiation,
      monitoring, dose adjustment, and management are less frequently addressed.
      Moreover, this information can be difficult to find, even in major textbooks.
      Rather than providing a comprehensive review of oral anticoagulants, this article
      emphasizes various practical aspects of therapy.

PMID- 29206590
TI  - Heparin therapy.
AB  - Preview Heparin is used worldwide to prevent arterial and venous thrombosis and
      to treat established thromboembolic disorders. It is also the mainstay of
      anticoagulation therapy for cardiopulmonary bypass and hemodialysis circuits. In
      this article, the authors examine the common indications for heparin therapy and
      describe the basic principles of heparin monitoring. Use of low-molecular-weight
      heparin is also briefly reviewed.

PMID- 29206591
TI  - Advances in anticoagulation.

PMID- 29206592
TI  - Dysthymic disorder.
AB  - Preview Dysthymic disorder, or dysthymia, is a mild to moderate depression that
      smolders for years despite brief moments of emotional reprieve in which the
      individual experiences a normal mood. These fleeting euthymic periods do not
      extend beyond a couple of months at a time. The up-and-down course is as
      potentially debilitating as that of major depression, yet dysthymia is
      surprisingly underdiagnosed. The authors review the diagnostic characteristics,
      comorbid conditions, and clinical approach to management of this insidious mood
      disorder.

PMID- 29206593
TI  - Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis
      of Diagnostic Accuracy.
AB  - Purpose To assess the diagnostic test accuracy and sources of heterogeneity for
      the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate
      low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade
      glioma (HGG) (WHO grade III or IV). Materials and Methods The Cochrane Library,
      Embase, Medline, and the Web of Science Core Collection were systematically
      searched by two librarians. Retrieved hits were screened for inclusion and were
      evaluated with the revised tool for quality assessment for diagnostic accuracy
      studies (commonly known as QUADAS-2) by two researchers. Statistical analysis
      comprised a random-effects model with associated heterogeneity analysis for mean
      differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate
      restricted maximum likelihood estimation method was used to describe the summary
      receiver operating characteristics curve and bivariate meta-regression. Results
      Ten studies involving 430 patients were included. The mean difference in MK
      between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z
      score equal to 5.86 (P < .001). The statistical heterogeneity was explained by
      glioma subtype, echo time, and the proportion of recurrent glioma versus primary
      glioma. The pooled area under the curve was 0.94 for discrimination of HGG from
      LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96)
      specificity. Heterogeneity was driven by neuropathologic subtype and DKI
      technique. Conclusion MK shows high diagnostic accuracy in the discrimination of
      LGG from HGG. (c) RSNA, 2017 Online supplemental material is available for this
      article.

PMID- 29206594
TI  - The Diagnostic Value of MR Imaging in Differentiating T Staging of Bladder
      Cancer: A Meta-Analysis.
AB  - Purpose To assess the diagnostic accuracy of magnetic resonance (MR) imaging for
      differentiating stage T1 or lower tumors from stage T2 or higher tumors and to
      analyze the influence of different imaging protocols in patients with bladder
      cancer. Materials and Methods A systematic literature search for original
      diagnostic studies was performed in PubMed, Medline, the Cochrane Library, and
      Web of Science. The methodologic quality of each study was evaluated by two
      independent reviewers who used the Quality Assessment of Diagnostic Accuracy
      Studies 2 tool. Data necessary to complete 2 * 2 tables were obtained, and
      patient, study, and imaging characteristics were extracted. Statistical analysis
      included data pooling, heterogeneity testing, sensitivity analyses, and forest
      plot construction. Results Seventeen studies (1449 patients with bladder cancer)
      could be analyzed. The pooled sensitivity and specificity of MR imaging were 0.90
      (95% confidence interval [CI]: 0.83, 0.94) and 0.88 (95% CI: 0.77, 0.94),
      respectively, for differentiating tumors staged T1 or lower from those staged T2
      or higher. Diffusion-weighted imaging and use of higher field strengths (3 T)
      improved sensitivity (0.92; 95% CI: 0.86, 0.96) and specificity (0.96; 95% CI:
      0.93, 0.98). Conclusion This meta-analysis demonstrated high diagnostic
      performance of MR imaging for differentiating T1 or lower tumors from T2 or
      higher tumors in patients with bladder cancer. Higher field strength (3 T) and
      the use of diffusion-weighted imaging can slightly help improve sensitivity and
      specificity. (c) RSNA, 2017.

PMID- 29206595
TI  - Assessment of Response to Transcatheter Arterial Chemoembolization with
      Doxorubicin-eluting Microspheres: Tumor Biology and Hepatocellular Carcinoma
      Recurrence in a 5-year Transplant Cohort.
AB  - Purpose To assess response to transcatheter arterial chemoembolization (TACE)
      based on immune markers and tumor biology in patients with hepatocellular
      carcinoma (HCC) who were bridged to liver transplantation, and to produce an
      optimized pretransplantation model for posttransplantation recurrence risk.
      Materials and Methods In this institutional review board-approved HIPAA-compliant
      retrospective analysis, 93 consecutive patients (73 male, 20 female; mean age,
      59.6 years; age range, 23-72 years) underwent TACE with doxorubicin-eluting
      microspheres (DEB) (hereafter, DEB-TACE) and subsequently underwent
      transplantation over a 5-year period from July 7, 2011, to May 16, 2016. DEB-TACE
      response was based on modified Response Evaluation Criteria in Solid Tumors.
      Imaging responses and posttransplantation recurrence were compared with
      demographics, liver function, basic immune markers, treatment dose, and tumor
      morphology. Treatment response and recurrence were analyzed with uni- and
      multivariate statistics, as well as internal validation and propensity score
      matching of factors known to affect recurrence to assess independent effects of
      DEB-TACE response on recurrence. Results Low-grade tumors (grade 0, 1, or 2)
      demonstrated a favorable long-term treatment response in 87% of patients
      (complete response, 49%; partial response, 38%; stable disease [SD] or local
      disease progression [DP], 13%) versus 33% of high-grade tumors (grade 3 or 4)
      (complete response, 0%; partial response, 33%; SD or DP, 67%) (P < .001). Of the
      93 patients who underwent treatment, 82 were followed-up after transplantation
      (mean duration, 757 days). Recurrence occurred in seven (9%) patients (mean time
      after transplantation, 635 days). Poor response to DEB-TACE (SD or DP) was
      present in 86% of cases and accounted for 35% of all patients with SD or DP (P <
      .001). By using only variables routinely available prior to liver
      transplantation, a validated model of posttransplantation recurrence risk was
      produced with a concordance statistic of 0.83. The validated model shows
      sensitivity of 83.6%, specificity of 82.6%, and negative predictive value of
      98.4%, which are pessimistic estimates. Conclusion Response to DEB-TACE is
      correlated with tumor biology and patients at risk for posttransplantation
      recurrence, and it may be associated with HCC recurrence after liver
      transplantation. (c) RSNA, 2017 Online supplemental material is available for
      this article.

PMID- 29206596
TI  - Value of a Computer-aided Detection System Based on Chest Tomosynthesis Imaging
      for the Detection of Pulmonary Nodules.
AB  - Purpose To assess the value of a computer-aided detection (CAD) system for the
      detection of pulmonary nodules on chest tomosynthesis images. Materials and
      Methods Fifty patients with and 50 without pulmonary nodules underwent both chest
      tomosynthesis and multidetector computed tomography (CT) on the same day. Fifteen
      observers (five interns and residents, five chest radiologists, and five
      abdominal radiologists) independently evaluated tomosynthesis images of 100
      patients for the presence of pulmonary nodules in a blinded and randomized
      manner, first without CAD, then with the inclusion of CAD marks. Multidetector CT
      images served as the reference standard. Free-response receiver operating
      characteristic analysis was used for the statistical analysis. Results The pooled
      diagnostic performance of 15 observers was significantly better with CAD than
      without CAD (figure of merit [FOM], 0.74 vs 0.71, respectively; P = .02). The
      average true-positive fraction and false-positive rate per all cases with CAD
      were 0.56 and 0.26, respectively, whereas those without CAD were 0.47 and 0.20,
      respectively. Subanalysis showed that the diagnostic performance of interns and
      residents was significantly better with CAD than without CAD (FOM, 0.70 vs 0.62,
      respectively; P = .001), whereas for chest radiologists and abdominal
      radiologists, the FOM with CAD values were greater but not significantly: 0.80
      versus 0.78 (P = .38) and 0.74 versus 0.73 (P = .65), respectively. Conclusion
      CAD significantly improved diagnostic performance in the detection of pulmonary
      nodules on chest tomosynthesis images for interns and residents, but provided
      minimal benefit for chest radiologists and abdominal radiologists. (c) RSNA, 2017
      Online supplemental material is available for this article.

PMID- 29206597
TI  - Quantitative Proteomic Analysis of the Hippocampus of Rats with GCR-Induced
      Spatial Memory Impairment.
AB  - NASA is planning future missions to Mars, which will result in astronauts being
      exposed to ~13 cGy/year of galactic cosmic radiation (GCR). Previous ground-based
      experiments have demonstrated that low (15 cGy) doses of 1 GeV/n 56Fe ions impair
      hippocampus-dependent spatial memory in rats. However, some irradiated rats
      maintain a spatial memory performance comparable to that seen in the sham
      irradiated rats, suggesting that some of these animals are able to ameliorate the
      deleterious effects of the GCR, while others are not. This rat model provides a
      unique opportunity to increase our understanding of how GCR affects
      neurophysiology, what adaptive responses can be invoked to prevent the emergence
      of GCR-induced spatial memory impairment, as well as the pathways that are
      altered when spatial memory impairment occurs. A label-free, unbiased proteomic
      profiling approach involving quantitative protein/peptide profiling followed by
      Cytoscape analysis has established the composition of the hippocampal proteome in
      male Wistar rats after exposure to 15 cGy of 1 GeV/n 56Fe, and identified
      proteins whose expression is altered with respect to: 1. radiation exposure and
      2. impaired spatial memory performance. We identified 30 proteins that were
      classified as "GCR exposure marker" (GEM) proteins (expressed solely or at higher
      levels in the irradiated rats but not related to spatial memory performance),
      most notably CD98, Cadps and GMFB. Conversely, there were 252 proteins that were
      detected only in the sham-irradiated samples, i.e., they were not detected in
      either of the irradiated cohorts; of these 10% have well-documented roles in
      neurotransmission. The second aspect of our data mining was to identify proteins
      whose expression was associated with either impaired or functional spatial
      memory. While there are multiple changes in the hippocampal proteome in the
      irradiated rats that have impaired spatial memory performance, with 203 proteins
      being detected (or upregulated) only in these rats, it would appear that spatial
      memory impairment may also arise from an inability of these rats to express "good
      spatial memory" (GSM) proteins, many of which play an important role in neuronal
      homeostasis and function, axonogenesis, presynaptic membrane organization and G
      protein coupled receptor (GCPR) signaling. It may be possible to use this
      knowledge to develop two alternative countermeasure strategies, one that
      preserves critical pathways prophylactically and one that invokes restorative
      pathways after GCR exposure.

PMID- 29206600
TI  - The changes before 'the change'.
AB  - Preview The effects of waning ovarian function start before menstruation stops,
      and they can be medically important. What changes should women expect, and what
      preventive health measures can they take? When is oral contraceptive therapy
      appropriate? How can irregular bleeding and decreased vaginal lubrication best be
      treated? Dr Bachmann addresses these and other questions in this discussion of
      appropriate healthcare for women in transition to the menopause.

PMID- 29206599
TI  - FTIR Microspectroscopy Probes Particle-Radiation Effect on HCT116 cells (p53+/+,
      p53-/-).
AB  - p53 is a crucial tumor suppressor and plays an important role in cell cycle
      arrest, DNA damage repair, promotion of cell senescence and apoptosis, prevention
      of DNA damage and maintaining genomic stability and integrity. It has been
      reported that p53 might also be related to radiation sensitivity, for which the
      involved effects and processes could be further examined biochemically at the
      molecular level. In this study, we explored a new spectroscopic approach to probe
      the radiation-induced biological effects related to p53. Infrared
      microspectroscopy was used to detect the metabolic changes related to p53 under
      particle radiation. After alpha-particle irradiation of HCT116 cells (p53+/+, p53
      /-), cell cycle arrest, DNA damage and lipid peroxidation in the cancer cells
      were observed using Fourier-transform infrared (FTIR) spectroscopy and
      microspectroscopy imaging. A remarkable difference in radiosensitivity between
      the two genotypes of cells was observed as well. This work provides a biochemical
      analysis of the p53-related radiation effects in cells and demonstrates the
      potential usefulness of FTIR microspectroscopy in the field of radiation
      research.

PMID- 29206598
TI  - Is there Unmeasured Indication Bias in Radiation-Related Cancer Risk Estimates
      from Studies of Computed Tomography?
AB  - Recently reported studies have associated radiation exposure from computed
      tomography (CT) scanning with small excess cancer risks. However, since existing
      medical records were used in these studies, they could not control for reasons
      for the CT scans and therefore, the results may have been confounded by
      indication. Here we conducted a study to estimate potential indication bias that
      could affect hazard ratios for colorectal, lung and female breast cancers by
      reasons for a CT scan. This involved a retrospective cohort study of electronic
      records from all patients aged 18-89 years without previous cancer diagnoses, who
      received at least one CT scan at Columbia University Medical Center in the period
      of 1994-2014. This investigation is not a study of CT-related cancer risks with
      adjustment for reasons, but an evaluation of the potential for confounding by
      indication in such studies. Among 75,968 patients, 212,487 CT scans were analyzed
      during a mean follow-up of 7.6 years. For colorectal and female breast cancers,
      no hazard ratio bias estimates for any of the CT reasons reached statistical
      significance. For lung cancer, significant biases occurred only in patients with
      unknown CT reasons and in patients with CTs for "abnormal findings" and in those
      with CTs for cancer- or nodule-related reasons. This retrospective cohort study
      among adults with >=1 CT scan evaluates, for the first time, CT reason-specific
      indication biases of potential CT-related cancer risks. Overall, our data suggest
      that, in studies of adults who underwent CT scans, indication bias is likely to
      be of negligible importance for colorectal cancer and female breast cancer risk
      estimation; for lung cancer, indication bias is possible but would likely be
      associated with only a small modulation of the risk estimate. Radiat. Res.

PMID- 29206601
TI  - Rheumatoid arthritis.
AB  - Preview The physical effects of rheumatoid arthritis go beyond joint pain and
      destruction. The disease may take a toll on numerous organ systems and has been
      shown to increase morbidity and mortality. How does it affect the lungs? The
      heart? The nervous system? In this article, Dr Bell answers these and other
      questions about the extra-articular manifestations of rheumatoid arthritis.

PMID- 29206602
TI  - Evaluation of involuntary weight loss.
AB  - Preview When a patient presents with involuntary weight loss, the etiologic
      considerations can be overwhelming. To plan a cost- effective workup, physicians
      need to be aware of the most common causes of weight loss and the tests that
      yield the most pertinent data. Drs Wise and Craig review the clinical studies on
      unintentional weight loss and suggest an initial approach to management.

PMID- 29206603
TI  - Acute, disruptive cough.
AB  - Preview Acute, disruptive cough is the second most common reason for which office
      visits are made and prescriptions written. But even when specific therapy is
      prescribed, a disruptive nonproductive cough may become nagging and prompt a
      patient to seek help again. The authors discuss the mechanism and causes of cough
      and describe symptomatic therapies in terms of their proposed mechanisms and
      indications.

PMID- 29206605
TI  - A Dictionary of Medical Puns.

PMID- 29206604
TI  - Radiographic evaluation of cervical spine trauma.
AB  - Preview A patient with a suspected cervical spine injury must be handled with the
      utmost care until fractures and other causes of instability have been excluded.
      In this article, the authors describe essential imaging techniques and discuss
      the evaluation of common- and some uncommon- injuries.

PMID- 29206606
TI  - Tuberculin skin testing.
AB  - Preview The incidence of tuberculosis in the United States is escalating at an
      alarming rate. Thus, it is imperative to detect the infection early so that
      chemoprophylaxis can be given before active disease has a chance to develop. The
      tuberculin skin test is simple, cheap, and effective and should be an integral
      part of evaluating not only high-risk groups but also the population at large. Dr
      Amin describes how to administer the test and interpret its results.

PMID- 29206607
TI  - Massive blood loss in trauma patients.
AB  - Preview An injured and bleeding patient who is pale, confused, hypotensive, and
      anuric is an obvious candidate for transfusion to counteract hemorrhagic shock.
      However, not all patients with shock have such classic signs, at least not until
      hemodynamic compromise becomes severe. The authors summarize the basic principles
      of patient evaluation and care in emergency situations. They also describe some
      adverse consequences of massive transfusions and present tips on how to avoid or
      minimize them.

PMID- 29206608
TI  - Thrombolytic therapy for acute myocardial infarction.
AB  - Preview There is little question that reperfusion therapy with thrombolytic
      agents benefits patients who meet the current eligibility requirements and
      receive therapy shortly after acute myocardial infarction. Less clear is whether
      this therapy would benefit and be safe for use in patients who are now deemed
      ineligible to receive it. The authors compare the three available intravenous
      thrombolytic agents, summarize the risks and benefits associated with thrombolyic
      therapy in various situations, and make recommendations based on their
      experience.

PMID- 29206609
TI  - Empathy and humanitarianism predict preferential moral responsiveness to in
      groups and out-groups.
AB  - The current research tests whether empathy-sharing others' emotions-and
      humanitarianism-recognizing the moral worth of all people-each predict moral
      responsiveness toward others but in ways that favor in-groups and out-groups,
      respectively. In Studies 1 and 2, empathy and humanitarianism differentially
      predicted preferential moral concern for in-groups and out-groups. In Study 3,
      humanitarianism predicted lower in-group-targeted prosociality and greater out
      group prosociality. In Study 4, empathy and humanitarianism predicted perceived
      moral obligation to in-groups and out-groups respectively. In Study 5, out-group
      obligation mediated between humanitarianism and allocations to out-group
      charities, and in-group obligation mediated between empathy and one of two in
      group charities. In sum, empathy and humanitarianism are associated with
      preferential morality via group-based obligation, suggesting that morality could
      be extended by altering empathy, humanitarianism, or group processes.

PMID- 29206610
TI  - Systolic hypertension in the elderly.
AB  - Preview Just when it appeared that diuretics were becoming obsolete in the attack
      against hypertension, they have come charging back to the fore. This is
      especially true in treatment of systolic hypertension in the elderly. The
      perspective on diuretics and their recommendations for administration have
      changed recently because of the results reported from several important clinical
      trials. This article reviews these findings and summarizes treatment
      implications.

PMID- 29206611
TI  - Right upper quadrant abdominal pain.
AB  - Preview Pain in the right upper quadrant of the abdomen can masquerade as a
      remarkable number of conditions. The gallbladder may be the cause, or other organ
      systems may be involved, including the lung, liver, pancreas, esophagus, stomach,
      or muscles of the thorax. When gallstones have been ruled out by ultrasonography,
      there are thus still a sobering number of possibilities, including,
      paradoxically, gallstones. Drs Rathgaber and Rex describe the differential
      diagnosis of this pain with clarity and common sense.

PMID- 29206612
TI  - Popliteal artery aneurysm.
AB  - Preview Symptoms of popliteal artery aneurysm may be nonexistent or transient,
      and a missed diagnosis can result in ischemic complications and limb amputation.
      In this article, Dr Seddon describes a case in which a patient presenting with
      "blue toes" was initially thought to have either a drug reaction or vasculitis.
      Dr Seddon also discusses important points in the evaluation and treatment of
      popliteal artery aneurysm.

PMID- 29206613
TI  - Modern coronary rehabilitation.
AB  - Preview The approach to rehabilitative care of coronary patients has changed
      dramatically in recent years. Emphasis has shifted from highly structured, formal
      programs to individualized regimens. Why have these changes come about? What are
      the current recommendations for exercise training? Can new technologies improve
      education and counseling of coronary patients? Dr Wenger, an advocate of the
      evolving patterns of coronary rehabilitative care, answers these and other
      questions and explains the advantages of the new approaches.

PMID- 29206614
TI  - Gonorrhea.
AB  - Preview Despite a recent decline in total cases, gonorrhea is on the rise in the
      adolescent population, particularly in black teenagers. Increases in sexual
      activity, drug abuse, and gonococcal resistance to antibiotics have contributed
      to the changing epidemiology of the disease. Dr Hawley explains how prevention
      and detection of gonorrhea can be improved and describes new, single-dose
      treatment with oral antibiotics.

PMID- 29206615
TI  - Chronic obstructive pulmonary disease.
AB  - Preview Because the dyspnea accompanying chronic obstructive pulmonary disease
      (COPD) is frightening, patients often become anxious and even fear death. As a
      result, they may retreat into a sedentary life-style and not seek medical care
      until much of their pulmonary function is lost. In this article, Dr Saroea
      discusses the therapeutic challenge that patients with COPD present and examines
      the major goals of management.

PMID- 29206616
TI  - Acute gouty arthritis.
AB  - Preview Gout is a painful and sometimes disabling form of arthritis that is
      easily managed if appropriate guidelines are observed. The main goals of
      management are termination of the acute attack and prevention of future attacks
      and complications. In this article, the authors review the important principles
      in diagnosis and treatment of this common disorder.

PMID- 29206617
TI  - Invasion of the 'killer' bees.
AB  - Preview How did Africanized honeybees get the reputation of being killers when
      their venom is no more potent than that of common European honeybees and they
      have less of it? Their highly defensive nature and their habit of attacking in
      great numbers probably account for the reports of alarming encounters between
      humans or animals and swarms of these bees. The authors discuss the bees'
      migration into the United States and summarize how to avoid and treat stings.

PMID- 29206618
TI  - Entrapment neuropathies.
AB  - Preview Entrapment neuropathies are common disorders that are often misdiagnosed.
      Accurate identification is important because the outlook for patients is good if
      appropriate treatment is initiated early. Drs Parachuri and Adams tell how to
      differentiate nerve entrapment from the neurologic, vascular, and articular
      diseases that it can resemble, and they discuss the diagnosis and treatment of
      nine common entrapment neuropathies.

PMID- 29206619
TI  - The antinuclear antibody test.
AB  - Preview The great majority of patients with systemic lupus erythematosus have
      positive antinuclear antibody (ANA) test results. However, other rheumatic and
      nonrheumatic diseases, certain drugs, infections, and pregnancy can also cause
      positive results. Thus, a negative ANA test is sometimes more helpful than a
      positive one when evaluating patients who do not clearly meet diagnostic criteria
      for rheumatic disease. The authors summarize appropriate use of the ANA test and
      how to interpret results.

PMID- 29206620
TI  - When Doctors Get Sick.

PMID- 29206622
TI  - Letter from the editor.

PMID- 29206621
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 29206623
TI  - Group identity and positive deviance in work groups.
AB  - This study examines why and how identity cognitions, including group
      identification and individual differentiation, influence the positive deviance of
      employees. We identify the risk-taking intention of employees as a critical
      psychological mechanism to overcome stigma-induced identity threat of positive
      deviance. The analysis of data collected from 293 members comprising 66 work
      teams reveals that the relationship between individual differentiation and
      positive deviance is partially mediated by risk-taking intention. The indirect
      effect of group identification on positive deviance through risk-taking intention
      is also significant and positive in groups with low conformity pressure, whereas
      the same indirect effect is neutralized in groups with high conformity pressure.
      The current analysis offers new insights into the way the group context and the
      identity cognition of members explain the development of positive deviance and
      workplace creativity.

PMID- 29206624
TI  - Use of Highways in the Sky and a virtual pad for landing Head Up Display
      symbology to enable improved helicopter pilots situation awareness and workload
      in degraded visual conditions.
AB  - Flight within degraded visual conditions is a great challenge to pilots of rotary
      wing craft. Environmental cues typically used to guide interpretation of speed,
      location and approach can become obscured, forcing the pilots to rely on data
      available from in-cockpit instrumentation. To ease the task of flight during
      degraded visual conditions, pilots require easy access to flight critical
      information. The current study examined the effect of 'Highways in the Sky'
      symbology and a conformal virtual pad for landing presented using a Head Up
      Display (HUD) on pilots' workload and situation awareness for both clear and
      degraded conditions across a series of simulated rotary-wing approach and
      landings. Results suggest that access to the HUD lead to significant improvements
      to pilots' situation awareness, especially within degraded visual conditions.
      Importantly, access to the HUD facilitated pilot awareness in all conditions.
      Results are discussed in terms of future HUD development. Practitioner Summary:
      This paper explores the use of a novel Heads Up Display, to facilitate rotary
      wing pilots' situation awareness and workload for simulated flights in both clear
      and degraded visual conditions. Results suggest that access to HUD facilitated
      pilots' situation awareness, especially when flying in degraded conditions.

PMID- 29206625
TI  - Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal
      cells.
AB  - MiR-204 and 211 enforced expression in murine mesenchymal stromal cells (MSCs)
      has been shown to induce adipogenesis and impair osteogenesis, through RUNX2 down
      modulation. This mechanism has been suggested to play a role in osteoporosis
      associated with obesity. However, two further fundamental MSC functions,
      chondrogenesis and hematopoietic supporting activity, have not yet been explored.
      To this end, we transduced, by a lenti-viral vector, miR-204 and 211 in a model
      primary human MSC line, opportunely chosen among our MSC collection for
      displaying all properties of canonical bone marrow MSCs, except adipogenesis.
      Enforced expression of miR-204&211 in these cells, rescued adipogenesis, and
      inhibited osteogenesis, as previously reported in murine MSCs, but, surprisingly,
      also damaged cartilage formation and hematopoietic supporting activity, which
      were never explored before. RUNX2 has been previously indicated as the target of
      miR-204&211, whose down modulation is responsible for the switch from
      osteogenesis to adipogenesis. However, the additional disruption of
      chondrogenesis and hematopoietic supporting activity, which we report here, might
      depend on diverse miR-204&211 targets. To investigate this hypothesis, permanent
      RUNX2 knock-down was performed. Sh-RUNX2 fully reproduced the phenotypes induced
      by miR-204&211, confirming that RUNX2 down modulation is the major event leading
      to the reported functional modification on our MSCs. It seems thus apparent that
      RUNX2, a recognized master gene for osteogenesis, might rule all four MSC
      commitment and differentiation processes. Hence, the formerly reported role of
      miR204&211 and RUNX2 in osteoporosis and obesity, coupled with our novel
      observation showing inhibition of cartilage differentiation and hematopoietic
      support, strikingly resemble the clinical traits of metabolic syndrome, where
      osteoarthritis, osteoporosis, anaemia and obesity occur together. Our
      observations, corroborating and extending previous observations, suggest that miR
      204&211-RUNX2 axis in human MSCs is possibly involved in the pathogenesis of this
      rapidly growing disease in industrialized countries, for possible therapeutic
      intervention to regenerate former homeostasis.

PMID- 29206626
TI  - Intensive smoking diminishes the differences in quality of life and exacerbation
      frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.
AB  - BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that
      is associated with low levels of circulating alpha-1-antitrypsin in serum. In
      comparison to the genotype PiZZ, PiSZ usually leads to lower risk of emphysema,
      better lung function and better survival. The aim of this study was to analyze
      the relationship between cigarette smoking (packyears) and the AATD genotypes
      (PiZZ and PiSZ) concerning quality of life (SGRQ), transfer factor of the lung
      for carbon monoxide (TLCO), forced expiratory volume in one second (FEV1) and
      exacerbation rate. METHODS: We compared PiZZ and PiSZ individuals from the German
      registry for individuals with AATD (AATDR) in univariate analysis and
      multivariate linear regression models. All subjects were stratified into three
      groups according to their cumulative nicotine consumption (0 py; 0 < py < 30; ?30
      py). RESULTS: 868 PiZZ individuals (mean age 52.6 +/- 12.8 years (43.5% female))
      and 114 PiSZ individuals (mean age 50.3 +/- 17.4 years (46.5% female)) were
      compared. In contrast to never- and intensive (ex-) smokers, moderate (ex-)
      smoking PiSZ individuals had a significantly better SGRQ total score (B = ?8.148;
      p = 0.020) and less exacerbations (B = ?0.354; p = 0.037) than individuals with
      PiZZ in multivariate analysis. CONCLUSIONS: The differences in quality of life
      and exacerbation frequency between PiZZ and PiSZ individuals diminish by
      intensive (ex-) smoking.

PMID- 29206627
TI  - Promoting physical activity in COPD: Insights from a randomized trial of a web
      based intervention and pedometer use.
AB  - RATIONALE: Low physical activity is highly prevalent among COPD patients and is
      associated with increased healthcare utilization and mortality and reduced HRQL.
      The addition of a website to pedometer use is effective at increasing physical
      activity; however, the timeline of change and impact of environmental factors on
      efficacy is unknown. METHODS: U.S. Veterans with COPD were randomized (1:1) to
      receive either (1) a pedometer and website which provided goal-setting, feedback,
      disease-specific education, and an online community forum or (2) pedometer alone
      for 3 months. Primary outcome was change in daily step count. Secondary outcomes
      included 6MWT distance, HRQL, dyspnea, depression, COPD knowledge, exercise self
      efficacy, social support, motivation, and confidence to exercise. Generalized
      linear mixed-effects models evaluated the effect of the pedometer plus website
      compared to pedometer alone. RESULTS: Data from 109 subjects (98.5% male, mean
      age 68.6 +/- 8.3 years) were analyzed. At 13 weeks, subjects in the pedometer
      plus website group had significant increases daily step count from baseline
      relative to the pedometer alone group (804 +/- 356.5 steps per day, p = 0.02).
      The pedometer plus website group had significant improvements in daily step count
      from baseline beginning in week 3 which were sustained until week 13. In subgroup
      analyses, the pedometer plus website attenuated declines in daily step count
      during the transition from summer to fall. No significant differences in
      secondary outcomes were noted between groups. CONCLUSIONS: A website added to
      pedometer use improves daily step counts, sustains walking over 3 months, and
      attenuates declines in physical activity due to season.

PMID- 29206628
TI  - Implementation gaps for asthma prevention and control.
AB  - Asthma and allergic diseases can start in childhood and persist throughout life,
      but could also be manifested later, at any time for still misunderstood reasons.
      They are major chronic multifactorial respiratory diseases, for which prevention,
      early diagnosis and treatment is recognized as a priority for the Europe's public
      health policy and the United Nations. Given that allergy triggers (including
      infections, rapid urbanization leading to loss in biodiversity, pollution and
      climate changes) are not expected to change in a foreseeable future, it is
      imperative that steps are taken to develop, strengthen and optimize preventive
      and treatment strategies. Currently there are good treatments for asthma, several
      risk factors are known (e.g., allergies, rhinitis, tobacco smoke) and tools to
      control the disease have been developed. However, we are still uncertain how to
      prevent patients from developing asthma and allergic diseases. In this paper, we
      list the positive and negative experiences in this field as well as analyze the
      missing links in the process. This critical analysis will be the basis of setting
      up an effective program for prevention and making, a process labeled as
      "implementation gaps".

PMID- 29206629
TI  - Biological effects of p38 MAPK inhibitor losmapimod does not translate to
      clinical benefits in COPD.
AB  - RATIONALE: p38 mitogen-activated protein kinase (MAPK) expression is increased in
      chronic inflammatory disease. Losmapimod, a p38 MAPK inhibitor, has been
      developed as a potential anti-inflammatory therapy in COPD. OBJECTIVES: To
      evaluate the effect of losmapimod in reducing exacerbations in subjects with
      moderate-to-severe COPD. METHODS: In this double-blind, parallel-group study,
      subjects at risk of COPD exacerbations and ?2% blood eosinophils at screening,
      were randomized 1:1 to losmapimod 15 mg or placebo (variable treatment duration:
      26-52 weeks). The primary endpoint was the annualized rate of moderate/severe
      exacerbations. Using a Bayesian framework, treatment success was defined as >90%
      posterior probability that the true ratio of the losmapimod/placebo exacerbation
      rate was <1. Lung function and health status (St George's Respiratory
      Questionnaire (SGRQ)) were also assessed. RESULTS: A planned interim analysis
      resulted in early study termination due to the low probability of a successful
      study outcome; a total of 94 subjects were randomized to placebo and 90 to
      losmapimod 15 mg, and 14 and 10 subjects respectively completed the study.
      Losmapimod treatment was not associated with an improvement in the adjusted
      posterior median annualized exacerbation rate (losmapimod/placebo ratio: 1.04
      (95% Cr I: 0.63, 1.73)). The posterior probability for the losmapimod/placebo
      annualized rate ratio being <1 was 0.44 (success criterion: >0.90). A
      statistically significant improvement in post-bronchodilator forced expiratory
      volume in 1 s was seen at Week 26, at the 5% significance level, with losmapimod
      treatment versus placebo (p = 0.007). Changes from baseline in SGRQ total score
      were similar in both groups. No new risks or safety signals were identified with
      losmapimod treatment. CONCLUSIONS: Losmapimod treatment did not reduce the rate
      of exacerbations in, subjects with COPD at high risk of exacerbation and ?2%
      blood eosinophils. These data do not support its use as a therapy in COPD in
      addition to standard of care.

PMID- 29206630
TI  - Does untreated obstructive sleep apnea cause secondary erythrocytosis?
AB  - BACKGROUND: The current literature suggests a relationship between obstructive
      sleep apnea (OSA) severity and hematocrit. However, the degree that OSA
      contributes to clinically significant erythrocytosis is uncertain. The aim of
      this study is to evaluate this association in a large study sample controlling
      for multiple confounders. METHODS: We evaluated consecutive subjects with
      suspected untreated OSA using multivariate analysis to test the associations
      between apnea-hypopnea index (AHI) and hematocrit. Subjects were evaluated with
      sleep studies, comprehensive sleep questionnaires, and detailed electronic
      medical record reviews to document their medical comorbidities, and demographic
      and laboratory information. RESULTS: 1604 consecutive veterans (age 57.6 +/- 13.4
      years, 92% male) were included in the analysis with 77.4% diagnosed with OSA.
      However, few included subjects (1.6%) had clinical erythrocytosis. OSA severity
      defined by AHI was not associated with hematocrit or clinically significant
      erythrocytosis. Rather, awake oxygen saturation (-0.17 points, p < 0.001) and
      mean nocturnal oxygen saturation (-0.08 points, p = 0.04) were inversely
      proportional to hematocrit (per standardized Z-score). Other factors including
      active tobacco, increased alcohol ingestion and exogenous testosterone therapy
      were associated with higher hematocrit. Although AHI was not predictive of
      erythrocytosis, having severe OSA was predictive of nocturnal hypoxemia (adjusted
      OR 7.4, p < 0.001). CONCLUSIONS: Hematocrit levels and presence of erythrocytosis
      appear not associated with OSA severity, but rather with hypoxemia as measured by
      awake and to a lesser extent mean nocturnal oxygen saturation. Nocturnal oximetry
      may provide diagnostic utility in the evaluation of unexplained secondary
      polycythemia and polysomongraphy may be warranted in those with unexplained
      nocturnal hypoxemia and erythrocytosis.

PMID- 29206631
TI  - Extrafine compared to non-extrafine particle inhaled corticosteroids in smokers
      and ex-smokers with asthma.
AB  - BACKGROUND: Smoking is as prevalent in asthmatics as in the general population.
      Asthmatic smokers benefit less from inhaled corticosteroids (ICS) than non
      smoking asthmatics, possibly due to more smoking-induced small airways disease.
      Thus targeting small airways may be important in treating asthmatic (ex-)smokers.
      We hypothesized that extrafine particle ICS improve small airways function more
      than non-extrafine particle ICS in asthmatic (ex-)smokers. METHODS: We performed
      an open-label, randomized, three-way cross-over study comparing extrafine
      beclomethasone (HFA-QVAR) to non-extrafine beclomethasone (HFA-Clenil) and
      fluticasone (HFA-Flixotide) in 22 smokers and 21 ex-smokers with asthma (?5
      packyears). RESULTS: Improvement from baseline in PD20 adenosine after using
      QVAR, Clenil or Flixotide was 1.04 +/- 1.71, 1.09 +/- 2.12 and 0.94 +/- 1.97
      doubling doses, mean +/- standard deviation (SD), respectively. The change from
      baseline in R5-R20 at PD20 adenosine after using QVAR, Clenil or Flixotide was
      ?0.02 +/- 0.27, 0.02 +/- 0.21, and ?0.02 +/- 0.31 kPa sL?1, mean +/- SD,
      respectively. The change in PD20 adenosine and R5-R20 at PD20 adenosine were
      neither statistically significant different between QVAR and Clenil (p = 0.86 and
      p = 0.82) nor between QVAR and Flixotide (p = 0.50 and p = 0.96). CONCLUSION:
      Similar effectiveness in improving small airways function was found for extrafine
      and non-extrafine particle ICS treatment for asthmatic smokers and ex-smokers.

PMID- 29206632
TI  - Unclassifiable-interstitial lung disease: Outcome prediction using CT and
      functional indices.
AB  - BACKGROUND: Unclassifiable-interstitial lung disease (uILD) represents a
      heterogeneous collection of pathologies encompassing those fibrosing lung
      diseases which do not fulfill current diagnostic criteria. We evaluated baseline
      and longitudinal functional and CT (visual and quantitative computer [CALIPER]
      analysis) variables to identify outcome predictors in uILD. METHODS: Consecutive
      patients with uILD on multidisciplinary review (n = 95) had baseline functional
      (FVC, DLco, CPI [composite physiologic index]) and CT features (visual
      evaluation: CT pattern, fibrosis extent, honeycombing presence, traction
      bronchiectasis severity, pulmonary artery (PA) diameter; CALIPER evaluation:
      fibrosis extent, pulmonary vessel volume (PVV)) examined in univariate and
      multivariate Cox regression models. Change in functional and CT variables were
      examined in a patient subset (n = 37), to identify indicators of outcome.
      RESULTS: On univariate analysis, CPI was the most powerful functional predictor
      of mortality (p < 0.0001). Visual traction bronchiectasis (p < 0.0001), PA
      diameter (p < 0.0001) and honeycombing presence (p = 0.0001) and CALIPER PVV (p =
      0.0003) were the strongest CT outcome predictors. On multivariate analysis of
      baseline indices, traction bronchiectasis (p = 0.003), PA diameter (p = 0.003)
      and CPI (p = 0.0001) independently predicted mortality. Colinearity with
      functional indices precluded the evaluation of CALIPER PVV in multivariate
      models. On evaluation of longitudinal variables, increasing CALIPER fibrosis
      extent was the strongest outcome predictor, and remained so following adjustment
      for baseline disease severity, and when FVC declines were marginal. CONCLUSIONS:
      In uILD patients, CPI, traction bronchiectasis severity and PA diameter
      independently predicted outcome at baseline. Increasing fibrosis extent measured
      by CALIPER was the most powerful index of outcome regardless of baseline disease
      severity and strongly predicted outcome in patients with marginal FVC declines.

PMID- 29206633
TI  - Exploration of the MUC5B promoter variant and ILD risk in patients with
      autoimmune myositis.
AB  - Interstitial lung disease (ILD) is common in patients with autoimmune myositis
      but factors that determine susceptibility are unknown. Familial and sporadic
      idiopathic pulmonary fibrosis (IPF) are strongly associated with a single
      nucleotide polymorphism in the promoter region of MUC5B (rs35705950). We sought
      to determine the relationship between MUC5B polymorphism expression and myositis
      ILD. The MUC5B minor allele frequency (MAF) was examined in 402 European American
      participants; 60 with idiopathic interstitial pneumonia (IIP), 208 with myositis
      ILD, and 134 unaffected controls. The MUC5B minor allele frequency was 26%, 8%,
      and 7% in those with non-myositis ILD, myositis-ILD, and unaffected controls,
      respectively. The MUC5B variant was associated with IIP (OR 4.10; p < 0.001). The
      MUC5B polymorphism was not significantly associated with myositis-ILD (OR 1.08; p
      = 0.80)]. We found MUC5B MAFs in our IIP cohort similar to published frequencies
      for subjects with familial and sporadic IPF. Overall, the MUC5B promoter variant
      does not appear to contribute to ILD risk in myositis patients.

PMID- 29206634
TI  - Long-term "real-life" safety of omalizumab in patients with severe uncontrolled
      asthma: A nine-year study.
AB  - BACKGROUND: Randomized Controlled Trials showed that omalizumab exhibited a good
      safety and tolerability profile in patients with moderate-to-severe asthma.
      However, safety data of long-term treatment with omalizumab are scarce. Our aim
      was to assess the safety of omalizumab in patients under long-term treatment in a
      real-life setting. METHODS: Difficult-to-control asthmatic patients treated with
      omalizumab up to 9 years were retrospectively evaluated. Mild to severe adverse
      events any and reasons for discontinuation were recorded. RESULTS: Ninety-one
      patients (26.4% males, mean age 49.9 +/- 14.9 years) were included: mean
      treatment length, 3.8 +/- 2.6 years; mean individual monthly dose, 514.5 +/-
      345.7 mg (range, 150-1200 mg). A total of 10,472 single injections were given
      cumulatively to the 91 patients (115 single injections per patients, on average,
      over a treatment period up to 9 years). Fifty-nine patients (64.8%) were treated
      for a period of time from 3 to 9 years, 14 of whom from 6 to 9 years. A high
      proportion of patients who discontinued treatment dropped out within the first
      year (18, 39.1%), mainly for reasons unrelated to treatment. Six patients (6.6%)
      discontinued omalizumab for treatment-related adverse events: arthralgia/myalgia
      (3 patients); urticaria, angioedema (1 patients); metrorrhagia (1 patient);
      relapsing herpes labialis (1 patient). Four other patients complained of mild
      adverse events (rhinitis/conjunctivitis, injection site reaction, fatigue,
      thrombosis) but continued the treatment. Anaphylaxis was not reported.
      CONCLUSIONS: Long-term treatment with omalizumab appears remarkably safe and well
      tolerated in real-life setting. Prolonged omalizumab treatment for many
      consecutive years did not increase the risk of side effects, particularly
      anaphylaxis.

PMID- 29206635
TI  - Domestic solid fuel combustion in an adult population in Nigeria: A cross
      sectional analysis of association with respiratory symptoms, quality of life and
      lung function.
AB  - BACKGROUND AND OBJECTIVES: We examined the association of respiratory symptoms,
      health status, and lung function with the use of solid fuel (wood, charcoal, coal
      or crop residue) for cooking or heating in a predominantly non-smoking
      population. METHODS: Using the protocol of the Burden of Obstructive Lung
      Diseases (BOLD) initiative, we collected representative population data using
      questionnaires and spirometry tests. We categorized solid fuel use into 'never
      user', 'ex user' and 'current user' based on responses to the survey. We
      developed regression models to evaluate the relation between use of solid fuel
      and the prevalence of respiratory symptoms, quality of life and lung function
      adjusting for confounding variables. RESULTS: Out of 1147 respondents with
      complete information on domestic fuel type, 33% were 'never-users', 19% were 'ex
      users' while 48% reported current use of solid fuel for domestic cooking and/or
      indoor heating. Compared with never-users, current solid fuel users were more
      likely to report cough (OR: 1.7, 95% CI: 1.0, 2.9), cough or phlegm (OR: 1.6, 95%
      CI: 1.0, 2.5) and the association was stronger among women (OR: 3.0, 95% CI: 1.3,
      7.1 and OR: 2.3, 95% CI: 1.1, 5.2, respectively). Current solid fuel users also
      had lower mental health status (coefficient: ?1.5, 95% CI: ?2.8, - 0.2) compared
      with the group of never-users. Current or previous domestic use of solid fuels
      for cooking or heating was not associated with higher prevalence of chronic
      airflow obstruction (FEV1/FVC < LLN). CONCLUSIONS: Using solid fuel for domestic
      cooking or heating was associated with a higher risk of cough or phlegm and a
      lower mental quality of life. However we found no significant effect in the
      prevalence of chronic airflow obstruction in Ife, Nigeria.

PMID- 29206636
TI  - Long-term effect of weight loss induced by bariatric surgery on asthma control
      and health related quality of life in asthmatic patients with severe obesity: A
      pilot study.
AB  - BACKGROUND: The weight loss induced by bariatric surgery (BS) improves asthma
      clinical control evaluated usually after a short time. The long-term effects of
      weight loss attained by BS on asthma control and health related-quality of life
      (HRQoL) in patients affected by asthma and obesity are not known. OBJECTIVE: To
      investigate the five-year effect of weight reduction induced by BS on asthma
      control, quality of life and pulmonary functional parameters in severely obese
      intermittent or mild-to-moderate asthmatic patients. METHODS: Twenty-six
      consecutive severe obese subjects with previous diagnosis of asthma with
      indication for laparoscopic adjustable gastric banding (LAGB) were enrolled into
      the study. Fifteen of them agreed to undertake the surgery (treatment group, TG)
      while the remaining eleven non-operated patients represented the control group
      (CG). Body mass index (BMI), Asthma Control Test (ACT), Mini Asthma Quality of
      Life Questionnaire (mini-AQLQ) and spirometric parameters were evaluated at
      baseline and after one and five years from surgery. RESULTS: Mean BMI of TG
      significantly decreased at one and five years after the surgery, while it
      remained unchanged in CG. After surgery, both the overall ACT and the mini-AQLQ
      score significantly improved in TG after one year, persisting improved after 5
      years (p < 0.001), while these outcomes remained unchanged in CG. As compared
      with the pre-surgery values, the percentage of predicted FEV1 and FVC
      significantly increased at five-year follow-up from surgery in TG, while it
      remained unchanged in CG. CONCLUSIONS: In severe obese asthmatic patients, the
      significant improvement of asthma control test and HRQoL, observed one year after
      LAGB, persists five years after surgery.

PMID- 29206637
TI  - Effects of inhaled corticosteroids /long-acting agonists in a single inhaler
      versus inhaled corticosteroids alone on all-cause mortality, pneumonia, and
      fracture in chronic obstructive pulmonary disease: A nationwide cohort study 2002
      2013.
AB  - BACKGROUND: Both inhaled corticosteroids (ICS) and long-acting ?-agonists (LABA)
      have been recommended for the treatment of severe/moderate chronic obstructive
      pulmonary disease (COPD), but mild COPD has not been frequently studied. METHODS:
      We performed a prospective cohort study to compare the effect of inhaled
      corticosteroid (ICS) and ICS/long-acting ?-agonist (LABA) in a single inhaler on
      all-cause mortality and adverse events, such as pneumonia and fracture, in
      patients with newly diagnosed chronic obstructive pulmonary disease (COPD). We
      used representative nationwide cohort data from the Korean National Health
      Insurance claims database (2002-2013). Patients who were at least 40-years-old,
      newly diagnosed with COPD, and prescribed ICS or ICS/LABA in a single inhaler (N
      = 1995). To analyze the data, we utilized a Cox's proportional hazard regression.
      RESULTS: Among the total of 1995 patients, 807 had severe COPD (FEV1 < 50%) and
      1188 had mild/moderate COPD (FEV1 ? 50%). The cumulative incidence and 5-year
      cumulative incidence of all-cause mortality was 59.5% and 29.6% for ICS users,
      and 35.8% and 20.2% for single inhaler ICS/LABA users, respectively. The adjusted
      hazard ratio (HR) of all-cause mortality for new ICS/LABA users, compared with
      that in new ICS users, was 0.77 (95% CI: 0.62-0.95) for the total population. For
      the severe and non-severe COPD groups, the adjusted HRs of all-cause mortality
      for new ICS/LABA users were 1.07 (95% CI: 0.65-1.76) and 0.70 (95% CI: 0.55
      0.89), respectively. There was no difference in the risk for the first
      hospitalization due to pneumonia between new ICS and ICS/LABA users among the
      total population (HR: 1.02; 95% CI: 0.79-1.34). The adjusted HR of the first
      hospitalization for fractures in new ICS/LABA users, compared with that in new
      ICS users, was 0.60 (95% CI: 0.39-0.92) for the total population. CONCLUSIONS:
      Among newly diagnosed COPD patients and new users of ICS or ICS/LABA, use of
      ICS/LABA in a single inhaler was associated with lowered risk of all-cause
      mortality and delayed first hospitalization for fracture, as compared with use of
      ICS alone. However, there was no significant difference in terms of first
      hospitalization for pneumonia.

PMID- 29206638
TI  - Work-related asthma in a sample of subjects with established asthma.
AB  - OBJECTIVE: To assess the impact of occupational exposure to irritants or
      sensitizers on the occurrence, recrudescence and worsening of asthma and to
      identify unrecognized cases of work related asthma (WRA) including Work
      Exacerbated Asthma (WEA) and Occupational Asthma (OA), in a general asthma clinic
      population sample. SETTING, DESIGN AND PARTICIPANTS: The study was a population
      based cross sectional survey. 1289 asthmatic subjects (from 15 to 46 yrs old)
      living in a vast district of Tuscany (Italy) were identified from the Medical
      Reimbursement Register of the National Health System. 893 subjects agreed to take
      part in the study. Subjects who were currently working or had worked in past were
      classified in different categories of occupational risk exposure (No, Low or
      High) according to the italian standard classification for industries and job
      titles, associated with the judgment of occupational hygiene experts. RESULTS:
      41% of subjects worked in industries and in job titles at risk for exposure to
      airway irritants and/or sensitizers, 48.6% reported an occupational exposure to
      gases, dust and fumes, more males than females. Prevalence of WEA and OA was
      higher in subjects who worked at higher risk exposure; these subjects reported a
      higher prevalence of markers of asthma severity (asthma control, level of
      treatment, FEV1) than subjects without WRA. Risk of WEA was significantly
      associated to female gender, older age, and self-reported exposure, while risk of
      OA was associated to job title with higher exposure risk to occupational
      asthmogens. CONCLUSIONS: Our study shows a high prevalence of WRA (especially
      WEA) associated with employment in industries and job titles at risk for airways
      sensitizers and/or irritants; data also support a role for occupational exposure
      in determining a poor asthma control and a higher level of asthma severity.

PMID- 29206639
TI  - Electrical impedance tomography in children with community acquired pneumonia:
      preliminary data.
AB  - BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive pulmonary
      function test that provides spatial and temporal information of changes in
      regional lung ventilation. We aimed to assess the feasibility of EIT as a
      supplementary tool in the evaluation of community acquired pneumonia in children.
      Furthermore, we performed a prospective evaluation of regional lung ventilation
      changes during a six-month follow-up period. METHODS: We enrolled otherwise
      healthy children aged 2-15 years with radiological diagnosis of community
      acquired pneumonia on admission at pediatric emergency department. Chest EIT was
      performed at enrollment, at three and six-months from baseline. RESULTS: Nineteen
      children were enrolled. A significant agreement between EIT and chest radiography
      in identifying the affected lung (left or right) was observed (Cohen K statistic
      = 0.73, 95% CI 0.5-0.98). Ventilation improvement was documented at three-month
      follow-up, but a full recovery only at six months. CONCLUSION: EIT reliably
      provides additional information on lung ventilation disorders due to CAP in
      children. It further allows bedside, real time and radiation free monitoring of
      lung functional recovery. Future studies are needed to expand the
      generalizability of this method and evaluate effectiveness on clinical practice.

PMID- 29206640
TI  - Trends in 30-day readmission rates after COPD hospitalization, 2006-2012.
AB  - BACKGROUND: Reduction in 30-day readmission rate after chronic obstructive
      pulmonary disease (COPD)-related hospitalization is a national objective.
      However, little is known about trends in readmission rates in recent years,
      particularly in priority populations defined by the Agency for Healthcare
      Research and Quality (AHRQ)(e.g., the elderly, women, racial/ethnic minorities,
      low-income and rural populations, and populations with chronic illnesses).
      METHODS: We conducted a retrospective cohort study using data from the State
      Inpatient Database of eight geographically-dispersed US states (Arkansas,
      California, Florida, Iowa, Nebraska, New York, Utah, and Washington) from 2006
      through 2012. We identified all COPD-related hospitalizations by patients ?40
      years old. The primary outcome was any-cause readmission within 30 days of
      discharge from the index hospitalization for COPD. RESULTS: From 2006 to 2012, a
      total of 845,465 hospitalizations at risk for 30-day readmissions were
      identified. Overall, 30-day readmission rate for COPD-related hospitalization
      decreased modestly from 20.0% in 2006 to 19.2% in 2012, an 0.8% absolute decrease
      (OR 0.991, 95%CI 0.989-0.995, Ptrend<0.001). This modest decline remained
      statistically significant after adjusting for patient demographics and
      comorbidities (adjusted OR 0.981, 95%CI 0.977-0.984, Ptrend<0.001). Similar to
      the overall population, the readmission rate over the 7-year period remained
      persistently high in most of AHRQ-defined priority populations. CONCLUSIONS: Our
      observations provide a benchmark for future investigation of the impact of
      Hospital Readmissions Reduction Program on readmissions after COPD
      hospitalization. Our findings encourage researchers and policymakers to develop
      effective strategies aimed at reducing readmissions among patients with COPD in
      an already-stressed healthcare system.

PMID- 29206641
TI  - Comparison of exercise training responses in COPD patients with and without Alpha
      1 antitrypsin deficiency.
AB  - BACKGROUND: The benefits of pulmonary rehabilitation (PR) on fatigue-resistant
      skeletal muscle fibre type I have been found to be smaller in COPD patients with
      alpha-1 antitrypsin deficiency (AATD) than in those without AATD. Alpha-1
      antitrypsin (AAT) augmentation therapy was suggested as a potential factor of
      influence. Whether this finding mirrors different improvements in 6-min walk
      distance (6MWD) between both groups remains unknown. METHODS: 140 patients with
      AATD-related COPD (phenotype PiZZ, FEV1: 31 +/- 8%pred.) and 280 COPD patients
      without AATD (FEV1: 31 +/- 8%pred.) were matched for baseline 6MWD and included
      in a retrospective analysis. AATD patients were divided into those "on"
      (AATDAUG+) or "off" (AATDAUG-) augmentation therapy. 6MWD was assessed pre and
      post an inpatient 4-week PR program. Plasma level of creatinine was analysed at
      baseline. RESULTS: In AATD and COPD patients with comparable initial 6MWD (331 +/
      106 m and 326 +/- 101 m, p = n.s.), improvements in 6MWD following PR were
      similar (+49 +/- 49 m and +53 +/- 52 m, intra-group change: p < 0.001). Notably,
      68% of AATD and 65% of COPD responded well with a clinically relevant 6MWD
      improvement of ?30 m. The improvement in 6MWD was independent of gender, age,
      pack years, SF36 mental score and body mass index. The augmentation therapy with
      AAT did not influence 6MWD outcome (AATDAUG+: +51 +/- 55 m, AATDAUG-: +47 +/- 40
      m, p = n.s.). Only in AATD group, higher baseline creatinine levels and lower
      6MWD were positive predictors for the PR-related increase in 6MWD. CONCLUSIONS:
      Independently of the genetic variant of AAT, COPD patients achieved the same
      training-related benefit in 6MWD. Augmentation therapy showed no effect on 6MWD
      adaptation during PR.

PMID- 29206642
TI  - Measurement of sirolimus concentrations in human blood using an automated
      electrochemiluminescence immunoassay (ECLIA): a multicenter evaluation.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) of sirolimus is essential in
      transplant recipients. We evaluated the performance of a new
      electrochemiluminescence immunoassay (ECLIA) for measuring sirolimus
      concentrations in whole blood at five European laboratories. METHODS: Study
      assessments included repeatability, intermediate precision and functional
      sensitivity (concentration at coefficient of variation [CV] of 20%) experiments.
      Method comparisons with liquid chromatography-tandem mass spectrometry (LC-MS/MS;
      reference method) and two immunoassays (chemiluminescent microparticle
      immunoassay [CMIA] and antibody-conjugated magnetic immunoassay [ACMIA]) were
      performed using native samples from patients with kidney transplants. RESULTS:
      Imprecision testing CVs were <=6.4% and <=10.7% across the sirolimus
      concentration range for both repeatability and intermediate precision,
      respectively. The ECLIA showed excellent functional sensitivity: the CV did not
      reach 20%; the CV at the assay's limit of quantitation (1.5 MUg/L) was 7.0%.
      Agreement between the ECLIA and LC-MS/MS using native kidney samples was close,
      with weighted Deming regression analysis yielding a slope of 1.05, an intercept
      of 0.154 MUg/L and a Pearson's correlation coefficient (r) of 0.94, while Bland
      Altman analysis showed a combined mean bias of 0.41 MUg/L (+/-2 standard
      deviation [SD], -1.96 to 2.68). The ECLIA also showed good correlation with the
      two other immunoassays: the CMIA (slope=0.91, intercept=0.112 MUg/L and r=0.89)
      and the ACMIA (slope=0.99, intercept=0.319 MUg/L and r=0.97). CONCLUSIONS: The
      ECLIA showed good precision, functional sensitivity and agreement with other
      methods of sirolimus measurement used in clinical practice, suggesting that the
      assay is suitable for TDM in transplant recipients and provides an alternative to
      LC-MS/MS.

PMID- 29206643
TI  - Emblica officinalis - Anti-obesity activity.
AB  - Context Emblica officinalis Gaertn. (family-Phyllanthaceae) fruits, known
      commonly as amla, is extensively used in Indian traditional system of medicine
      for the treatment of various disorders. The ethanolic E. officinalis extract is
      reported to have various activity such as antidiabetic, antihyperlipidemic and
      antioxidant activity in experimental animals. Objective To evaluate anti-obesity
      effect of aqueous E. officinalis extract in murine model of high fat diet (HFD)
      induced obesity. Materials and methods Male Wistar rats fed with HFD (20
      g/day/rat, p.o) for a period of 42 days were used to induce obesity. Aqueous E.
      officinalis extract (20 mg/kg bw) administered orally to HFD-fed rats from day 8
      to 50 days for a period of 42 days. Body weight gain, serum lipids, insulin and
      leptin parameters were measured. Results Oral feeding of the aqueous E.
      officinalis extract (20 mg/kg) to HFD-induced obese rats for a period of 42 days
      resulted in significant reduction in body weight gain, insulin, leptin, lipids as
      compared to rats fed HFD alone. Further, the extract also showed significant
      increase in high density lipoprotein (HDL-C) levels. Discussion and conclusions
      These results show that aqueous E. officinalis extract possess significant anti
      obesity potential.

PMID- 29206644
TI  - Antinociceptive and antioxidant activities of Hunteria umbellata stem bark:
      possible role of the serotonergic, opioidergic and dopaminergic pathways.
AB  - Background Hunteria umbellata (HU) (K. Schum) is used in ethnomedicine for the
      management of pain, diabetes mellitus and dysmenorrhoea. This study evaluated the
      analgesic and antioxidant activities of aqueous extract of HU stem bark and the
      possible mechanism(s) of action. Methods The antinociceptive effect of HU was
      evaluated using acetic acid mouse writhing, tail flick, hot plate and formalin
      induced paw licking models. To establish the possible mechanism(s) of action of
      HU, separate group of animals were pretreated with naloxone (1 mg/kg, i.p.),
      atropine (1 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.), ondansetron (1 mg/kg,
      i.p.) and phenoxybenzamine (0.1 mg/kg, i.p.), 15 min before HU. The in vivo and
      in vitro antioxidant potential was evaluated using established methods. Results
      The extract at 150 and 300 mg/kg, significantly (p<0.05) reduced the number of
      writhes and paw licking times and increased pain threshold in writhing assay, paw
      licking and hotplate tests respectively. Pretreatment of animals with
      ondansetron, naloxone and haloperidol, significantly (p<0.05 and p<0.01)
      attenuated the analgesic activity of HU. The extract demonstrated significant
      (p<0.05) radical scavenging activity (IC50 0.39 ug/mL), with high phenol content
      and reducing property. The total phenol content was 124.19 per gram of gallic
      acid. In vivo antioxidant assay showed significant (p<0.05) increase in catalase
      and superoxide levels. Conclusions Results obtained in this study suggest the
      involvement of serotonergic, opioidergic and dopaminergic pathways in the
      analgesic effect of HU stem bark, in addition to its potent antioxidant
      potential.

PMID- 29206645
TI  - Corrigendum to: Functional brain MRI in patients complaining of
      electrohypersensitivity after long term exposure to electromagnetic fields.

PMID- 29206646
TI  - Argatroban and Bivalirudin for Perioperative Anticoagulation in Cardiac Surgery.

PMID- 29206647
TI  - Microvascular Permeability after an Acute and Chronic Salt Load in Healthy
      Subjects: A Randomized Open-label Crossover Intervention Study.
AB  - BACKGROUND: Sodium-induced microcirculatory changes, endothelial surface layer
      alterations in particular, may play an important role in sodium-mediated blood
      pressure elevation. However, effects of acute and chronic sodium loading on the
      endothelial surface layer and microcirculation in humans have not been
      established. The objective of this study was to assess sodium-induced changes in
      blood pressure and body weight as primary outcomes and also in microvascular
      permeability, sublingual microcirculatory dimensions, and urinary
      glycosaminoglycan excretion in healthy subjects. METHODS: Twelve normotensive
      males followed both a low-sodium diet (less than 50 mmol/day) and a high-sodium
      diet (more than 200 mmol/day) for eight days in randomized order, separated by a
      crossover period. After the low-sodium diet, hypertonic saline (5 mmol
      sodium/liter body water) was administered intravenously in 30 min. RESULTS: Both
      sodium interventions did not change blood pressure. Body weight increased with
      2.5 (95% CI, 1.7 to 3.2) kg (P < 0.001) after dietary sodium loading. Acute
      intravenous sodium loading resulted in increased transcapillary escape rate of I
      labeled albumin (2.7 [0.1 to 5.3] % cpm . g . h; P = 0.04), whereas chronic
      dietary sodium loading did not affect transcapillary escape rate of I-labeled
      albumin (-0.03 [-3.3 to 3.2] % cpm . g . h; P = 1.00), despite similar increases
      of plasma sodium and osmolality. Acute intravenous sodium loading coincided with
      significantly increased plasma volume, as assessed by the distribution volume of
      albumin, and significantly decreased urinary excretion of heparan sulfate and
      chondroitin sulfate. These changes were not observed after dietary sodium
      loading. CONCLUSIONS: Our results suggest that intravenous sodium loading has
      direct adverse effects on the endothelial surface layer, independent of blood
      pressure.

PMID- 29206648
TI  - Relationship between plasma protein S levels and apolipoprotein C-II in Japanese
      middle-aged obese women and young nonobese women.
AB  - : Protein S, a nonenzymatic cofactor to activated protein C, presents in two
      forms in plasma, free form and in a complex with C4b-binding protein. The aim of
      this study was to determine the association of plasma protein S levels with the
      variables related to cardiovascular disease risk. The relationships between
      plasma protein S levels with lipids, inflammation markers, and adiposity were
      first examined on middle-aged obese women (n = 62), then on young nonobese women
      (n = 160) to verify the findings in the obese women. Total and free protein S
      antigen levels in middle-aged obese women, approximately half being in a
      postmenopausal state and suffered from dyslipidemia, correlated negatively with
      estradiol and positively with triglycerides, total cholesterol, LDL cholesterol,
      apoA-II, apoB, apoC-II, apoC-III, apoE, hemoglobin A1c, and protein C, whereas
      there was no correlation with HDL cholesterol, apoA-I, BMI, visceral fat area,
      blood pressure, or factor VII activity. Multiple linear regression analyses
      revealed that protein C, apoC-II, and fibrinogen were significant predictors of
      total protein S antigen levels, accounting for 51.9% of variance, and apoC-II as
      a singular significant predictor for free protein S antigen levels (12.3% of
      variance). In young nonobese women, most being normolipidemic, apoC-II was also
      selected as a significant predictor of total protein S antigen levels, but not of
      free protein S antigen levels. The positive relationship between plasma protein S
      levels and apoC-II, a key regulator of triglycerides hydrolysis, may contribute
      to the pathogenesis of increased concentrations of plasma protein S.

PMID- 29206649
TI  - The importance of the microbiome in pediatrics and pediatric infectious diseases.
AB  - PURPOSE OF REVIEW: Emerging research on the pediatric microbiome implicates the
      importance of the microbiome on the development of the immune system, nervous
      system, and growth. Changes to the microbiome during infancy are associated with
      the development of chronic illnesses such as asthma and inflammatory bowel
      disease. Additionally, the microbiome provides protection against certain
      pathogens, affects vaccine responses, and alters drug metabolism. This review
      highlights what is known about the microbiome, the establishment of a healthy
      microbiome and the significance that changes to the microbiome composition have
      on growth and health of children and adolescents. RECENT FINDINGS: Vaginal
      delivery, breastfeeding, maternal health, and nutrition help shape a healthy
      microbiome. Caesarian delivery, formula feeding, and antibiotic use perturb the
      microbiome and are associated with the development of type II diabetes, asthma,
      allergic diseases, and obesity later in life. Specific interventions using pre
      and probiotics in multiple settings are under investigation with limited success.
      SUMMARY: A better understanding of the microbiome and the interaction with the
      immune system may help guide interventions to alter the microbiome toward a state
      of lifelong health.

PMID- 29206650
TI  - Surgical treatment of femoroacetabular impingement after slipped capital femoral
      epiphysis.
AB  - PURPOSE OF REVIEW: Femoroacetabular impingement (FAI) post slipped capital
      femoral epiphysis (SCFE) may lead to degenerative changes on the hip. We have
      reviewed the current procedures in the literature, aiming to correct the SCFE to
      prevent FAI and the ones that treat FAI post SCFE. RECENT FINDINGS: The trends of
      managing moderated or severe SCFE is to correct the displacement by reduction and
      fixation with articular hematoma decompression in unstable hips and Dunn modified
      procedure even for unstable and stable situations. However, after FAI is settled,
      the options are osteochondroplasty by arthroscopy or surgical hip dislocation,
      associated or not to subtrocanteric osteotomy. SUMMARY: Femoroacetabular
      impingement may occur in mild slips and certainly occur in cases of moderate and
      severe slips. The initial management depends on the severity and the stability of
      the slip.The modified Dunn procedure is a good option for the treatment of
      unstable SCFEs. Gentle closed reduction with capsulotomy (Parsch) may be
      considered whenever the surgeon is not comfortable with the modified Dunn
      procedure.Hips with open physis and stable moderate or severe SCFE, the modified
      Dunn procedure can be indicated. Cases with closed physis are managed with
      intertrochanteric osteotomy combined with osteoplasty.In the presence of
      symptomatic FAI secondary to SCFE, one should consider arthroscopic osteoplasty
      or surgical hip dislocation (with or without osteotomies) as treatment options.

PMID- 29206651
TI  - Novel therapeutic strategies and targets in advanced uveal melanoma.
AB  - PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration
      approved or effective treatment options for advanced-stage uveal melanoma. In
      this article, we focus on therapeutic targets in pathways/mechanisms associated
      with common mutations in uveal melanoma. We review the challenges associated with
      targeting of these pathways and novel treatment strategies. RECENT FINDINGS:
      Common mutations that promote uveal melanoma initiation and progression include
      alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1
      associated protein 1 (BAP1). Mutant GNAQ/GNA11 induces constitutive activation of
      tumorigenic pathways such as extracellular signal-regulated kinase (ERK)1/2 and
      yes-associated protein. Inhibition of mitogen-activated protein kinase kinase
      (MEK) downstream of ERK1/2, however, was shown in trials to have limited clinical
      benefit. Recent reports suggested that combination therapies of MEK inhibition
      and modulators of mechanisms of drug resistance may improve tumor responses to
      MEK inhibitors. BAP1 has been shown to be involved in modulating chromatin
      dynamics and deubiquitination of proteins. Hence, epigenetic inhibitors are being
      investigated in BAP1 mutant uveal melanoma. However, other functions of BAP1,
      such as in DNA damage repair and cell cycle regulation, indicate additional
      targets for treatment of BAP1 mutant uveal melanoma. In addition, the frequent
      delayed development of uveal melanoma macrometastases is likely due to cellular
      dormancy mechanisms. Nuclear receptor subfamily 2, group F, member 1 and
      transforming growth factor beta 2 were among factors that have been shown in
      other cancers to induce dormant phenotypes. SUMMARY: Findings from studies in
      uveal melanoma and in other cancers provide evidence for potential strategies
      that may be tested preclinically and clinically in advanced-stage uveal melanoma
      to improve treatment outcome and overall survival of patients.

PMID- 29206652
TI  - Suprachoroidal shunts.
AB  - PURPOSE OF REVIEW: This article reviews recent studies evaluating the efficacy
      and safety of ab externo and ab interno suprachoroidal shunts designed to augment
      uveoscleral outflow in patients with open angle glaucoma. RECENT FINDINGS: The
      Gold Shunt and STARflo are placed into the suprachoroidal space via an ab externo
      approach, while the CyPass Micro-Stent and iStent Supra are inserted ab interno
      through a clear corneal incision. A small randomized clinical trial suggested
      similar efficacy among two different models of the Gold Shunt and the Ahmed
      glaucoma valve. The pivotal multicenter, randomized COMPASS trial showed that the
      CyPass Micro-Stent combined with cataract surgery is more effective than cataract
      surgery alone through 2 years. Study results suggest a favorable safety profile
      for each suprachoroidal device and intraocular pressure-lowering to the mid-to
      high teens with an associated reduction in medication burden. Given the relative
      novelty of these procedures, it is currently unknown whether fibroblastic
      proliferation within the suprachoroidal space may limit their long-term success.
      SUMMARY: Renewed interest in the suprachoroidal space has led to the development
      of new biocompatible glaucoma implants. Ab interno devices are easily combined
      with cataract surgery and preserve conjunctiva for future incisional glaucoma
      surgery. Additional data regarding the long-term efficacy and late complications
      of suprachoroidal shunts are needed.

PMID- 29206653
TI  - Ginkgo biloba and its potential role in glaucoma.
AB  - PURPOSE OF REVIEW: This study will review the research on the effect of ginkgo
      biloba extract (GBE) on patients with glaucoma. RECENT FINDINGS: GBE appears to
      increase ocular blood flow in those with glaucoma. However, data on visual field
      outcomes are inconclusive. SUMMARY: GBE has been shown to have antioxidant and
      vascular effects, making it potentially effective in treating glaucoma. Published
      data are limited but show an increase in ocular blood flow after GBE
      administration. Conclusive evidence is lacking regarding the effect of GBE on
      clinical outcomes in glaucoma patients such as visual field performance.

PMID- 29206654
TI  - Descemet membrane endothelial keratoplasty and glaucoma.
AB  - PURPOSE OF REVIEW: The aim of this review is to describe the relationship between
      Descemet membrane endothelial keratoplasty (DMEK) and glaucoma. RECENT FINDINGS:
      Glaucoma after DMEK is a serious complication that may cause permanent visual
      loss, affect donor endothelial cells and graft survival. The mechanisms of raised
      intraocular pressure (IOP) after DMEK include reverse pupillary block in the
      early postoperative period, and steroid response in the late phase. The reduced
      risk of immunogenic graft rejection after DMEK necessitates a shorter duration of
      steroids, which may in turn reduce the risk of steroid response. On the other
      hand, eyes with preexisting glaucoma that undergo DMEK may have a poorer
      prognosis than those without glaucoma. SUMMARY: Early recognition and treatment
      of raised IOP is important after DMEK. Accurate IOP measurements after DMEK may
      be difficult to obtain because of the presence of an air bubble, corneal oedema,
      and corneal irregularities. A prophylactic peripheral iridectomy is recommended
      to prevent reverse pupillary block. Patients should posture face-up and be
      evaluated in the early postoperative period, as patients may be asymptomatic
      despite raised IOP. In order to reduce the risk of steroid response, weaker
      steroids may be prescribed after 1-3 months without adverse effects on DMEK
      outcomes.

PMID- 29206657
TI  - Dual bronchodilator therapy for chronic obstructive pulmonary disease: evidence
      for the efficacy and Safety of fixed dose combination treatments in the setting
      of recent guideline updates.
AB  - PURPOSE OF REVIEW: Recent updates to the GOLD guidelines emphasize the use of
      combination LABA and LAMA bronchodilators for patients with chronic obstructive
      pulmonary disease with persistent dyspnea despite monotherapy or frequent
      exacerbations despite LAMA monotherapy. There are several commercially available
      LABA/LAMA fixed dose combination inhalers, which are likely to become the
      principle therapy for many patients with COPD. RECENT FINDINGS: In the last 4
      years, there have been a number of large clinical trials evaluating the efficacy
      and safety of combined LAMA and LABA bronchodilators. LAMA/LABA fixed dose
      combination therapies have consistently demonstrated clinically significant
      improvements to airway obstruction, dyspnea, and quality of life whenever
      compared with placebo, and more modest improvements compared with bronchodilator
      monotherapies and combined bronchodilator/inhaled corticosteroid therapy.
      SUMMARY: New guidelines emphasize combination bronchodilators as a mainstay of
      therapy for many patients with symptomatic COPD and there are several new
      combination bronchodilator therapies available to patients. It is important for
      physicians and patients to understand the range and degree of expected clinical
      effects and the safety profiles of these new medications.

PMID- 29206656
TI  - HIV integration sites and implications for maintenance of the reservoir.
AB  - PURPOSE OF REVIEW: To provide an overview of recent research of how HIV
      integration relates to productive and latent infection and implications for cure
      strategies. RECENT FINDINGS: How and where HIV integrates provides new insights
      into how HIV persists on antiretroviral therapy (ART). Clonal expansion of
      infected cells with the same integration site demonstrates that T-cell
      proliferation is an important factor in HIV persistence, however, the driver of
      proliferation remains unclear. Clones with identical integration sites harbouring
      defective provirus can accumulate in HIV-infected individuals on ART and
      defective proviruses can express RNA and produce protein. HIV integration sites
      differ in clonally expanded and nonexpanded cells and in latently and
      productively infected cells and this influences basal and inducible
      transcription. There is a growing number of cellular proteins that can alter the
      pattern of integration to favour latency. Understanding these pathways may
      identify new interventions to eliminate latently infected cells. SUMMARY: Using
      advances in analysing HIV integration sites, T-cell proliferation of latently
      infected cells is thought to play a major role in HIV persistence. Clonal
      expansion has been demonstrated with both defective and intact viruses.
      Production of viral RNA and protein from defective viruses may play a role in
      driving chronic immune activation. The site of integration may determine the
      likelihood of proliferation and the degree of basal and induced transcription.
      Finally, host factors and gene expression at the time of infection may determine
      the integration site. Together these new insights may lead to novel approaches to
      elimination of latently infected cells.

PMID- 29206655
TI  - Pathophysiology, clinical presentation, and treatment of coma and acute kidney
      injury complicating falciparum malaria.
AB  - PURPOSE OF REVIEW: Cerebral impairment and acute kidney injury (AKI) are
      independent predictors of mortality in both adults and children with severe
      falciparum malaria. In this review, we present recent advances in understanding
      the pathophysiology, clinical features, and management of these complications of
      severe malaria, and discuss future areas of research. RECENT FINDINGS: Cerebral
      malaria and AKI are serious and well recognized complications of severe malaria.
      Common pathophysiological pathways include impaired microcirculation, due to
      sequestration of parasitized erythrocytes, systemic inflammatory responses, and
      endothelial activation. Recent MRI studies show significant brain swelling in
      both adults and children with evidence of posterior reversible encephalopathy
      syndrome-like syndrome although targeted interventions including mannitol and
      dexamethasone are not beneficial. Recent work shows association of cell-free
      hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults
      and children. Paracetamol protected renal function likely by inhibiting cell-free
      mediated oxidative stress. It is unclear if heme-mediated endothelial activation
      or oxidative stress is involved in cerebral malaria. SUMMARY: The direct causes
      of cerebral and kidney dysfunction remain incompletely understood. Optimal
      treatment involves prompt diagnosis and effective antimalarial treatment with
      artesunate. Renal replacement therapy reduces mortality in AKI but delayed
      diagnosis is an issue.

PMID- 29206658
TI  - Lung function trajectories and chronic obstructive pulmonary disease: current
      understanding and knowledge gaps.
AB  - PURPOSE OR REVIEW: Population-based studies have shown a significant
      heterogeneity in patients with chronic obstructive pulmonary disease (COPD),
      regarding both the attainment of maximal lung function and the subsequent decline
      over time. This review will highlight recent advances in the understanding of
      lung function trajectory in COPD, focusing on factors that influence peak adult
      lung function, markers of accelerated lung function decline and pharmacologic
      interventions in early phases of the disease. RECENT FINDINGS: Recent data have
      shown that individuals with lower lung function early in life will go on to
      develop lower forced expiratory volume in 1 s (FEV1) in adulthood. Smoking can
      amplify the effect of specific childhood exposures on maximal adult lung
      function. Clinical symptoms such as chronic mucous hypersecretion and the
      biomarker club cell secretory protein have been associated with lung function
      decline over time. New computed tomography imaging markers also show promise as a
      way to detect early small airway disease, but need to be examined more
      longitudinally. In addition to these advances, a slower decline in FEV1 has been
      demonstrated in two randomized clinical trials studying tiotropium and inhaled
      fluticasone. SUMMARY: A better understanding of lung function development and
      eventual decline in those at risk for progression to COPD will aide in a
      precision medicine approach, in which markers for those at risk of low maximal
      lung function and accelerated decline are identified. Targeted therapy can then
      be used early to modify disease activity and outcomes.

PMID- 29206659
TI  - What are the dominant cytokines in early rheumatoid arthritis?
AB  - PURPOSE OF REVIEW: Rheumatoid arthritis is a systemic disease of evolving immune
      dysregulation that culminates in joint destruction and disability. The principle
      by which pro-inflammatory cytokines may be therapeutically targeted to abrogate
      disease is well established, but has yet to translate into reliable cures for
      patients. Emerging insights into cytokine-mediated pathobiology during rheumatoid
      arthritis development are reviewed, and their implications for future treatment
      strategies considered. RECENT FINDINGS: Accumulating data highlight cytokine
      perturbations before the clinical onset of rheumatoid arthritis. Some of these
      have now been linked to the arthritogenic activation of autoantibodies and
      associated pain and bone destruction in affected joints. These observations
      suggest cytokines may trigger the transition from systemic immunity to arthritis.
      Cytokine exposure could furthermore 'prime' synovial stromal cells to perpetuate
      a dominant pro-inflammatory environment. By facilitating cross-talk between
      infiltrating immune cells and even sustaining ectopic lymphoid structure
      development in some cases, cytokine interplay ultimately underpins the failure of
      arthritis to resolve. SUMMARY: Successful therapeutic stratification will depend
      upon an increasingly sophisticated appreciation of how dominant players amongst
      cytokine networks vary across time and anatomical space during incipient
      rheumatoid arthritis. The prize of sustained remission for all patients justifies
      the considerable effort required to achieve this understanding.

PMID- 29206661
TI  - The need and opportunity for donation after circulatory death worldwide.
AB  - PURPOSE OF REVIEW: The global shortage of organ donors will not be resolved
      solely by relying on deceased donation following a brain death determination
      (DBD). Expansion of deceased donation after circulatory death (DCD) will be
      needed to address the shortfall of organs for transplantation. Approximately 120
      000 organ transplants are performed each year; however, the WHO estimates that
      this number of transplants only resolves 10% of the annual worldwide transplant
      need. RECENT FINDINGS: The report addresses the opportunity of DCD expansion by
      evaluating the DCD potential that is not being realized, the utility of DCD
      enabling DBD to emerge in some clinical situations, by the effectiveness of a
      donor registry in achieving DCD, and by the current clinical research of heart,
      lung, and liver transplantation from DCD. SUMMARY: The future of deceased
      donation must include DCD and ex-vivo organ repair if the organ shortage is to be
      reconciled even partially to the ongoing demand. Although the religious and legal
      impediments have been overcome to determine brain death, the possibility of DCD
      has not been addressed. A program of DCD is feasible in all countries with
      transplantation services. The excellent results following kidney and lung
      transplantation suggest opportunities of heart and liver transplantation should
      be the focus of needed DCD accomplishment in the near future.

PMID- 29206662
TI  - Surgery Versus Radiation Treatment for High-Grade Neuroendocrine Cancer of
      Uterine Cervix: A Surveillance Epidemiology and End Results Database Analysis.
AB  - OBJECTIVES: The objective of this study was to assess treatment and other factors
      impacting survival in cervical high-grade neuroendocrine carcinoma (HGNEC).
      METHODS/MATERIALS: We identified patients with cervical HGNECs diagnosed during
      1988 to 2012 in the Surveillance Epidemiology and End Results database. We
      determined overall survival by International Federation of Gynecology and
      Obstetrics stages and by local treatment modalities, that is, radical surgery
      versus external beam radiation treatment (EBRT) plus brachytherapy using Kaplan
      Meier analysis with log-rank test. We also determined factors of age, stage, and
      treatment modality impacting survival using proportional hazard analysis.
      RESULTS: We identified 832 cases of cervical HGNECs in the database. After
      excluding cases with incomplete stage data, the International Federation of
      Gynecology and Obstetrics stages I to IV distributions were 196 (28.0%), 69
      (9.9%), 175 (25.0%), and 260 patients (37.1%), respectively. Radical surgery and
      primary radiotherapy yielded similar 5-year overall survival for stages I (61% vs
      53%, P = 0.27), II (48% vs 28%, P = 0.308), and III (33% vs 28%, P = 0.408)
      patients. External beam radiation treatment plus brachytherapy did not yield
      superior survival than EBRT alone in stage I (48% vs 49%, P = 0.799), II (37% vs
      20%, P = 0.112), or III (25% vs 32%, P = 0.636) patients. Age (P = 0.004) and
      stage (stage II: hazard ratio [HR], 1.78, P = 0.013; stage III: HR, 2.42; P <
      0.001) were independent factors impacting survival but not local treatment
      modality (EBRT: HR, 1.30, P = 0.17; EBRT plus brachytherapy: HR, 1.16; P =
      0.417). CONCLUSIONS: Patients with cervical HGNECs had poor prognosis. Primary
      treatment by radical surgery or external beam radiotherapy with or without
      brachytherapy yielded equally poor survival.

PMID- 29206660
TI  - Recent developments in systemic lupus erythematosus pathogenesis and applications
      for therapy.
AB  - PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) pathogenesis is complex.
      Aberrancies of immune function that previously were described but not well
      understood are now becoming better characterized, in part through recognition of
      monogenic cases of lupus-like disease. RECENT FINDINGS: We highlight here recent
      descriptions of metabolic dysfunction, cytokine dysregulation, signaling defects,
      and DNA damage pathways in SLE. Specifically, we review the effects of signaling
      abnormalities in mammalian target of rapamycin, Rho kinase, Bruton's tyrosine
      kinase, and Ras pathways. The importance of DNA damage sensing and repair
      pathways, and their influence on the overproduction of type I interferon in SLE
      are also reviewed. SUMMARY: Recent findings in SLE pathogenesis expand on
      previous understandings of broad immune dysfunction. These findings have clinical
      applications, as the dysregulated pathways described here can be targeted by
      existing and preclinical therapies.

PMID- 29206663
TI  - Letter From Editor: January 2018.

PMID- 29206665
TI  - Lean Mass and Functional Recovery in Men With Hip Fracture: A Short-Term
      Prospective Pilot Study.
AB  - OBJECTIVE: The aim of the study was to assess the capability of different
      definitions of low appendicular lean mass (aLM) to predict the short-term
      functional recovery in men with hip fracture. DESIGN: We investigated 80 of 95
      men with hip fracture admitted consecutively to a rehabilitation hospital. Body
      composition was assessed by dual-energy x-ray absorptiometry. Functional recovery
      after inpatient rehabilitation was evaluated using Barthel Index scores. RESULTS:
      The patients with aLM above the cutoff value of 19.75 kg indicated by the
      Foundation for the National Institutes of Health (FNIH) had significantly higher
      Barthel Index scores than those with aLM below the cutoff value (P = 0.002).
      Patients' categorization according to the same threshold (aLM = 19.75 kg) was
      significantly associated with a Barthel Index score of 85 or higher after
      adjustment for age, cognitive impairment, hip fracture type, co-morbidities, and
      medications (odds ratio = 7.17, 95% confidence interval = 1.43-35.94, P = 0.017).
      Conversely, patients' categorization according to neither Baumgartner's cutoff
      value (7.26 kg/m) for aLM/height nor Foundation for the National Institutes of
      Health cutoff value (0.789) for aLM divided by body mass index was significantly
      associated with the Barthel Index scores. CONCLUSIONS: Categorization according
      to the Foundation for the National Institutes of Health threshold for aLM, but
      not to the Foundation for the National Institutes of Health threshold for
      aLM/body mass index or Baumgartner's threshold for aLM/height, was associated
      with the short-term recovery in activities of daily living after a hip fracture
      in men.

PMID- 29206666
TI  - Immediate Effects of Simultaneous Application of Transcutaneous Electrical Nerve
      Stimulation and Ultrasound Phonophoresis on Active Myofascial Trigger Points: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of the study was to investigate the efficacy of phonophoresis
      with combined therapy on active myofascial trigger points. PARTICIPANTS: One
      hundred participants with acute mechanical neck pain and at least one active
      myofascial trigger point in the upper trapezius were randomly assigned into four
      equal groups. INTERVENTION: Groups consisted of diclofenac phonophoresis with
      combined therapy, diclofenac phonophoresis, ultrasound (US) with coupling gel,
      and sham US and applied for 10 mins over myofascial trigger points. MEASUREMENTS:
      Measurements included pressure pain threshold and active cervical lateral
      flexion. RESULTS: There were statistically significant improvements in
      postintervention pressure pain threshold and range of motion values in treatment
      groups (P < 0.0001). As for the sham US, no significant difference was found
      between the preintervention and postintervention values (P > 0.05). Bonferroni
      correction test revealed that there was a significant difference between all the
      four groups in pressure pain threshold values (P < 0.0001); however, it was
      nonsignificant (P > 0.05) for range of motion. CONCLUSIONS: Diclofenac
      phonophoresis with combined therapy, phonophoresis, and US were all effective in
      increasing pressure pain threshold values and range of motion. In addition,
      phonophoresis with combined therapy was shown to be superior over phonophoresis,
      and phonophoresis was superior over US in terms of reducing pain sensitivity.
      However, none of the treatment groups were found to be superior over the other in
      increasing range of motion.

PMID- 29206664
TI  - Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study
      of the Sankai Gynecology Study Group.
AB  - OBJECTIVE: Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous
      carcinoma of the uterine cervix, characterized by aggressive clinical behavior
      and absence of high-risk human papillomavirus. We conducted this study to
      evaluate the chemosensitivity of GAS compared with that of usual-type
      endocervical adenocarcinoma (UEA) in patients who had been enrolled in our
      previous study. METHODS: Of 52 patients from our previous phase 2 study (SGSG005)
      of neoadjuvant chemotherapy with docetaxel and carboplatin for stage IB2 to IIB
      nonsquamous cervical cancer, 47 (stage IB2, 12; stage IIA2, 7; stage IIB, 28)
      were enrolled in this study with written informed consent. The biopsy specimens
      before neoadjuvant chemotherapy and surgical specimens after chemotherapy were
      centrally reviewed based on the updated World Health Organization classification
      (2014). RESULTS: Of 47 patients with nonsquamous cell carcinoma, 20 (42.6%) were
      diagnosed with UEA, 13 (27.7%) with GAS, 12 (25.5%) with adenosquamous carcinoma,
      and 1 patient each (2%) with small cell carcinoma and serous carcinoma.
      Consequently, 33 patients, consisting of 20 patients with UEA and 13 patients
      with GAS, were eligible for the current study. The response rate of GAS was
      significantly lower than that of UEA (46.2% vs 85.0%, P = 0.048). Of 16 cases of
      stage II UEA, 11 (68.8%) were downstaged on microscopic examination of
      postsurgical specimens, but none of the 8 patients with stage II GAS showed any
      response (P < 0.01). Two inoperative tumors were GAS. With a median follow-up
      duration of 56 months, the 5-year progression-free and overall survival rates of
      GAS were significantly worse than those of UEA (38.5% vs 75.0% [P = 0.011] and
      36.9% vs 90.0% [P < 0.001], respectively). CONCLUSIONS: These findings suggest
      that GAS should be distinguished from UEA by its chemoresistance, necessitating
      an alternative treatment strategy established for this distinct subtype of
      endocervical adenocarcinoma.

PMID- 29206667
TI  - Total Pancreatectomy With Intraportal Islet Autotransplantation as a Treatment of
      Chronic Pancreatitis in Patients With CFTR Mutations.
AB  - OBJECTIVES: Chronic pancreatitis (CP) is an infrequent but debilitating
      complication associated with CFTR mutations. Total pancreatectomy with islet
      autotransplantation (TPIAT) is a treatment option for CP that provides pain
      relief and preserves beta-cell mass, thereby minimizing the complication of
      diabetes mellitus. We compared outcomes after TPIAT for CP associated with CFTR
      mutations to CP without CTFR mutations. METHODS: All TPIATs performed between
      2002 and 2014 were retrospectively reviewed: identifying 20 CFTR homozygotes
      (cystic fibrosis [CF] patients), 19 CFTR heterozygotes, and 20 age-/sex-matched
      controls without CFTR mutations. Analysis of variance and chi tests were used to
      compare groups. RESULTS: Baseline demographics were not different between groups.
      Postoperative glycosylated hemoglobin and C-peptide levels were similar between
      groups, as were islet yield and rate of postoperative complications. At 1 year,
      40% of CF patients, 22% of CFTR heterozygotes, and 35% of control patients were
      insulin independent. CONCLUSION: Total pancreatectomy with islet
      autotransplantation is a safe, effective treatment option for CF patients with
      CP, giving similar outcomes for those with other CP etiologies.

PMID- 29206669
TI  - Reply to "Full or Limited Enhanced Recovery Program? That Is the Question".

PMID- 29206670
TI  - Surgical Treatment of Perihilar Cholangiocarcinoma: Resection or Transplant?

PMID- 29206668
TI  - Treatment Patterns and Clinical Outcomes in Patients With Metastatic
      Gastroenteropancreatic Neuroendocrine Tumors Treated in the Community Practice
      Setting in the United States.
AB  - OBJECTIVE: This study was conducted to understand treatment patterns and clinical
      outcomes in metastatic gastroenteropancreatic neuroendocrine tumor patients
      treated in a large community oncology network. METHODS: This retrospective study
      used the McKesson Specialty Health/US Oncology Network iKnowMed electronic health
      record database with supplemental chart review. Eligibility criteria included a
      metastatic neuroendocrine tumor diagnosis between January 1, 2008, and to
      December 31, 2012; at least 2 US Oncology Network visits; and age at least 18
      years. Follow-up was through October 31, 2014. RESULTS: Among the 229 patients
      identified, median age was 64.0 years, 52.4% were male, 69.4% were white, and
      62.9% were overweight/obese. Primary tumor sites included small bowel (47.6%),
      pancreas (31.4%), and stomach/colorectum (21.0%). There were 16.2% under
      observation without treatment, 52.4% received only somatostatin analogs (SSAs),
      and 31.4% received chemotherapy/targeted therapy during treatment. In the first
      line setting (n = 192), 77% received SSAs, 12% received chemotherapy, and 10.9%
      received targeted therapy. Fifty percent of patients receiving octreotide had a
      relative dose intensity of less than 85%, and 16.7% received above-label dose.
      Toxicities of SSAs included diarrhea (18.2%), abdominal pain (16.9%), and fatigue
      (13.5%). Median overall survival from diagnosis was 68.0 months (95% confidence
      interval, 57.1 to not reached). CONCLUSIONS: Most metastatic
      gastroenteropancreatic neuroendocrine tumor patients received systemic treatment
      with SSAs. Patient treatment used an individualized dosing approach. Overall
      survival and toxicity were consistent with the published literature.

PMID- 29206671
TI  - Higher Patient Numbers-Stronger Evidence?

PMID- 29206672
TI  - Full or limited enhanced recovery program? That is the question.

PMID- 29206673
TI  - PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in
      Patients With Surgically Resected Esophageal Cancer.
AB  - OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD
      L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination
      in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention
      for its roles in tumor immunology and as an immune-based therapeutic target. To
      ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1
      expression and the presence or absence of TILs is required. METHODS: Using a
      nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD
      L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by
      immunohistochemical analysis. The Cox proportional hazard model was used to
      compute the hazard ratio (HR) for mortality. RESULTS: Compared with PD-L1
      negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse
      overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08
      2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05-2.67; P =
      0.033]. TIL positivity was significantly correlated with longer overall survival
      (log-rank P < 0.0001) and high CD8 expression (P < 0.0001). A stratification
      based on PD-L1 expression and TIL status was also significantly associated with
      overall survival (log rank P < 0.0001). CONCLUSIONS: PD-L1 expression was
      associated with an unfavorable clinical outcome in esophageal cancer, supporting
      its role as a prognostic biomarker. In addition, the combination with TIL status
      enabled further classification patients according to clinical outcome. PD-L1
      expression and TIL status may serve as predictive tissue biomarkers and can be
      used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1
      pathways.

PMID- 29206674
TI  - Long-Term Outcome and Causes of Death for Working-Age Patients Hospitalized Due
      to Acute Pancreatitis With a Median Follow-Up of 10 Years.
AB  - OBJECTIVE: To examine long-term survival and causes of death among working-age
      patients with acute pancreatitis (AP) compared with the normal population.
      SUMMARY OF BACKGROUND DATA: Few studies have investigated long-term survival
      after AP and recurrent AP compared with the normal population; moreover, results
      from those studies are difficult to compare, due to suboptimal control
      populations and wide variations in follow-up times. METHODS: This retrospective,
      registry-based study included 1644 patients with AP, aged 18 to 64 years,
      admitted to Oulu University Hospital in 1995 to 2012. Patient data were compared
      with data from 8220 age- and sex-matched controls that resided in the hospital
      district area. RESULTS: Alcohol was the main etiologic factor causing 71.4% of
      the cases. During the median follow-up time of 9.5 years, mortality was 24.2% in
      the study group and 6.3% in the control group (P < 0.001). Alcohol-related
      factors caused 39.4% of deaths and alcohol AP was the main single cause of death
      (16.3%) in the study group. Of all fatal AP cases, 42.9% were related to
      recurrence. Survival was similar among patients with nonalcohol AP and controls.
      CONCLUSION: The long-term mortality among patients admitted to the hospital due
      to (mainly alcohol induced) AP was 4 times higher than that in the age- and sex
      matched control population. The significant difference in the causes of death
      between patients with alcohol AP and controls could be explained by alcohol
      related diseases. Occurrences of AP without an alcohol etiology had a minimal
      impact on survival.

PMID- 29206675
TI  - The John L. Cameron Legacy Factor: Further Quantifying His Impact.

PMID- 29206676
TI  - Hepatobiliary Hands of Hopkins.
AB  - OBJECTIVE: This historical perspective documents the role that John L. Cameron
      played in advancing hepatobiliary research, education, and surgery at Johns
      Hopkins in the 1970s, 1980s, and 1990s. SUMMARY OF BACKGROUND DATA: Dating back
      to William S. Halsted in the 19th century, leaders of the Department of Surgery
      at Johns Hopkins have been interested in hepatobiliary disease and surgery. John
      L. Cameron had broad hepato-pancreato-biliary (HPB) interests when he completed
      his surgical training. Over the next 3 decades, he focused on the pancreas. As a
      result, many faculty and trainee hepatobiliary careers were launched. METHODS:
      This perspective is based on 18 years of service as a surgical resident and
      faculty member at Johns Hopkins. An extensive literature search on the
      hepatobiliary publications of Halsted, Trimble, Blalock, Longmire, Zuidema, and
      Cameron was undertaken for this manuscript. Numerous hepatobiliary publications
      from Johns Hopkins from the 1970s, 1980s, 1990s, and early 2000s were also
      reviewed. RESULTS: John L. Cameron's early biliary interests included stones,
      infections, malignancies, and strictures. He was innovative with respect to
      portal hypertension and Budd-Chiari surgery and supportive when liver
      transplantation emerged in the 1980s. Volume-outcome studies in the 1990s
      included hepatic and complex biliary surgery. He supported and encouraged studies
      of biliary lithotripsy, laparoscopic cholecystectomy, clinical pathways,
      hepatobiliary cysts, and gallstone pathogenesis. CONCLUSION: Lessons learned by
      many who worked with John L. Cameron included the importance of mentorship,
      innovation, friendship, and collaboration. He taught leadership and change
      management by example. He fostered a multidisciplinary approach and encouraged
      randomized controlled trials.

PMID- 29206677
TI  - Benchmarking Complications Associated with Esophagectomy.
AB  - OBJECTIVE: Utilizing a standardized dataset with specific definitions to
      prospectively collect international data to provide a benchmark for complications
      and outcomes associated with esophagectomy. SUMMARY OF BACKGROUND DATA: Outcome
      reporting in oncologic surgery has suffered from the lack of a standardized
      system for reporting operative results particularly complications. This is
      particularly the case for esophagectomy affecting the accuracy and relevance of
      international outcome assessments, clinical trial results, and quality
      improvement projects. METHODS: The Esophageal Complications Consensus Group
      (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries
      developed a standardized platform for recording complications and quality
      measures associated with esophagectomy. Using a secure online database
      (ESODATA.org), ECCG centers prospectively recorded data on all resections
      according to the ECCG platform from these centers over a 2-year period. RESULTS:
      Between January 2015 and December 2016, 2704 resections were entered into the
      database. All demographic and follow-up data fields were 100% complete. The
      majority of operations were for cancer (95.6%) and typically located in the
      distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation
      (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open
      procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses
      were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of
      patients. The overall incidence of complications was 59% with the most common
      individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%).
      Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred
      in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo
      complications >= IIIb occurred in 17.2% of patients. Readmissions occurred in
      11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively.
      CONCLUSION: Standardized methods provide contemporary international benchmarks
      for reporting outcomes after esophagectomy.

PMID- 29206678
TI  - Quality Improvement in Bariatric Surgery: The Impact of Reducing Postoperative
      Complications on Medicare Payments.
AB  - OBJECTIVE: To determine the temporal relationship between reducing surgical
      complications and costs, using the study population of bariatric surgery.
      BACKGROUND: Understanding the relationship between quality and costs has
      significant implications for the business case of investing in performance
      improvement. An unprecedented focus on safety in bariatric surgery has led to
      substantial reductions in complication rates over time, making it an ideal
      patient population in which to examine this relationship. METHODS: We performed a
      retrospective review of Medicare beneficiaries undergoing bariatric surgery in
      the years 2005 to 2006 and 2013 to 2014 (total N = 37,329 patients, 562
      hospitals). Hospitals were ranked into quintiles based on their degree of
      improvement in risk and reliability-adjusted 30-day rates of serious
      complications across the time periods. Multivariable regression was used to
      calculate corresponding changes in average price-standardized payments for each
      quintile of hospitals. RESULTS: We found a strong association between reductions
      in complications and decreased Medicare payments. The top 20% of hospitals had a
      decrease in average serious complication rate of 7.3% (10.0%-2.7%; P < 0.001) and
      an average per-patient savings of $4861 (95% confidence interval $3921-5802).
      Conversely, the bottom 20% of hospitals had smaller decrease in complication rate
      of 0.8% (4.4% to 3.6%; P < 0.001) and a smaller average savings of $2814 (95%
      confidence interval $2139-3490). CONCLUSIONS: When analyzing Medicare patients
      undergoing bariatric surgery, hospitals with the largest reductions in serious
      postoperative complications had the greatest decrease in per-patient payments.
      This study demonstrates the potential savings associated with quality improvement
      in high-risk surgical procedures.

PMID- 29206679
TI  - Predicting Intestinal Adaptation in Pediatric Intestinal Failure: A Retrospective
      Cohort Study.
AB  - OBJECTIVE: The primary goal in intestinal failure (IF) is adaptation and enteral
      autonomy (EA). Our goals were to determine the proportion of patients treated for
      IF by an established intestinal rehabilitation program who achieved EA and to
      assess the predictors of EA. BACKGROUND: There have been considerable
      advancements in the management of IF over the last 15 years, children with short
      bowel syndrome with a reduction in mortality. Several studies have discussed
      variables that may influence the ability to attain EA; however, majority were
      written when mortality rates were considerably higher compared with the current
      contemporary experience. METHODS: A retrospective analysis of infants <12 months
      with short bowel syndrome referred between 2006 and 2013 (n = 120). Data was
      collected on IF-related factors and nutritional intake. The cohort was stratified
      based on achievement of EA. Statistical testing completed using t test, Chi
      Square, and Cox Proportional Hazards regression (P < 0.05). RESULTS: EA was
      achieved in 84 (70.0%) patients. Patients who remained parenteral nutrition
      dependent were more likely to have volvulus (1.2 vs 22.2%, P < 0.001), shorter
      percent residual small bowel (29.4 vs 68.6%; P < 0.0001) and colon length (64.6
      vs 86.0%; P = 0.001), and no ileocecal valve (61.1 vs 29.8%; P = 0.05). Mortality
      was also decreased in those who achieved EA (4 vs 22%; P = 0.004). Percent
      residual small bowel (HR = 1.03; 95% CI 1.02-1.03) and colon (HR = 1.01; 95% CI
      1.00-1.02) length were positively associated with EA, while number of septic
      episodes was negatively associated (HR = 0.95; 95% CI 0.91-0.99). CONCLUSION:
      Seventy percent of infants with IF achieved EA. Residual small and large bowel
      length were the most important predictors of EA and septic events had a negative
      impact.

PMID- 29206680
TI  - Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and
      immune checkpoint inhibitors.
AB  - PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of
      a variety of immune approaches being evaluated in the therapy of acute myeloid
      leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T
      cell engager antibodies, and immune checkpoint blockade via antibodies targeting
      cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD
      1). RECENT FINDINGS: The stellar success of immune therapies that harness the
      power of T cells in solid tumors and an improved understanding of the immune
      system in patients with hematologic malignancies have resulted in major efforts
      to develop immune therapies for the treatment of patients with AML. Monoclonal
      antibodies in AML therapy include naked antibodies against AML surface antigens
      such as CD33 (e.g. lintuzumab) or CD38 (e.g. daratumumab), antibodies conjugated
      to toxins in various anti-CD33 (gemtuzumab ozogamicin, SGN33A, IMGN779) and anti
      CD123 (SL-401, SGN-CD123A) formulations, and antibodies conjugated to radioactive
      particles such as I or Ac-labeled anti-CD33 or anti-CD45 antibodies. Additional
      antigenic targets of interest in AML include CLL1, CD38, CD25, TIM3, FLT3, and
      others. Approaches to harness the body's own T cells against AML include
      antibodies that recruit and induce cytotoxicity of tumor cells by T cells
      (bispecific T-cell engager [BiTE] such as CD33 x CD3 (e.g. AMG 330) or CD123 x
      CD3 (e.g. flotetuzumab, JNJ-63709178) or antibodies that block immune checkpoint
      receptors CTLA4 (e.g. ipilimumab) or PD1/PD-L1 (e.g. nivolumab, pembrolizumab,
      avelumab) on T cells, unleashing the patients' T cells against leukemic cells.
      SUMMARY: The ongoing trials and well designed correlative interrogation of the
      immune system in patients treated on such trials will further enhance our
      understanding and clinical application of immune therapies as single-agent and
      combination approaches for the treatment of AML.

PMID- 29206681
TI  - Primary care management of ulcerative colitis.
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease marked by mucosal
      inflammation. UC has an impact on quality of life and places a financial burden
      on the healthcare system. This article focuses on the impact, presentation,
      diagnosis and classification, systemic manifestations, complications, management,
      and treatment associated with UC.

PMID- 29206682
TI  - Research Artifact-Real or Not? Only the Discussion Can Tell Us for Sure.

PMID- 29206683
TI  - Surprised by Benefit in Pediatric Palliative Care Research.

PMID- 29206684
TI  - The Diagnosis of Acute Compartment Syndrome: A Critical Analysis Review.

PMID- 29206685
TI  - Intelligence and specific cognitive functions in intellectual disability:
      implications for assessment and classification.
AB  - PURPOSE OF REVIEW: Current diagnostic criteria for intellectual disability
      categorize ability as measured by IQ tests. However, this does not suit the new
      conceptualization of intellectual disability, which refers to a range of
      neuropsychiatric syndromes that have in common early onset, cognitive
      impairments, and consequent deficits in learning and adaptive functioning. A
      literature review was undertaken on the concept of intelligence and whether it
      encompasses a range of specific cognitive functions to solve problems, which
      might be better reported as a profile, instead of an IQ, with implications for
      diagnosis and classification of intellectual disability. RECENT FINDINGS: Data
      support a model of intelligence consisting of distinct but related processes.
      Persons with intellectual disability with the same IQ level have different
      cognitive profiles, based on varying factors involved in aetiopathogenesis.
      Limitations of functioning and many biopsychological factors associated with
      intellectual disability are more highly correlated with impairments of specific
      cognitive functions than with overall IQ. SUMMARY: The current model of
      intelligence, based on IQ, is of limited utility for intellectual disability,
      given the wide range and variability of cognitive functions and adaptive
      capacities. Assessing level of individual impairment in executive and specific
      cognitive functions may be a more useful alternative. This has considerable
      implications for the revision of the International Classification of Diseases and
      for the cultural attitude towards intellectual disability in general.

PMID- 29206686
TI  - Adverse childhood experiences in children with autism spectrum disorder.
AB  - PURPOSE OF REVIEW: Recent years have shown an uptick in studies assessing
      bullying and other adverse childhood experiences (ACEs) in children with autism
      spectrum disorder (ASD). This article reviews extant findings, and points to gaps
      in the literature. RECENT FINDINGS: Children with ASD are bullied by peers at a
      rate three to four times that of nondisabled peers with negative impacts on
      academic functioning and mental health symptoms, including increased risk for
      suicidality. Children with ASD are also at enhanced risk for other ACES,
      particularly parental divorce and income insufficiency, and as observed in the
      general population, children with ASD who experience an increased number of ACES
      are at elevated risk for comorbid psychiatric and medical health problems.
      Children with ASD with an elevated number of ACES also experience a delay in ASD
      diagnosis and treatment initiation. There is no evidence of increased risk of
      child maltreatment within the ASD population. SUMMARY: As bullying and other
      adverse experiences are common and associated with deleterious outcomes in
      children with ASD, there is a need for additional research on intervention
      strategies to prevent and mitigate the impact of these experiences. Ongoing work
      on the assessment of trauma experiences and PTSD symptoms in children on the
      spectrum is also needed.

PMID- 29206687
TI  - A review of clinical trials of oxytocin in Prader-Willi syndrome.
AB  - PURPOSE OF REVIEW: PWS is a severe developmental disability for which there is no
      known treatment. The oxytocin system is currently a primary target for
      intervention. The aim of this article is to review the evidence for the efficacy
      of intranasal oxytocin in PWS. RECENT FINDINGS: To date, there have been five
      clinical trials of oxytocin in PWS. Four of these studies reported that oxytocin
      improved behaviors. However, each of these studies suffered important limitations
      that likely influenced the findings. For example, one study did not include a
      control group. Another study did not statistically analyze the effects of
      oxytocin on behavior. The final two studies used study-specific measures for
      which psychometric properties have not been assessed. SUMMARY: Because of these
      limitations, the most appropriate conclusion to draw from the existing studies is
      that there is currently no convincing evidence that intranasal oxytocin improves
      symptoms of PWS. However, this does not mean that oxytocin is not involved in
      PWS. Rather, it suggests that further work is needed to understand the nature of
      the PWS oxytocin abnormality.

PMID- 29206688
TI  - Current developments in the genetics of Rett and Rett-like syndrome.
AB  - PURPOSE OF REVIEW: This article reviews the current molecular genetic studies,
      which investigate the genetic causes of Rett syndrome or Rett-like phenotypes
      without a MECP2 mutation. RECENT FINDINGS: As next generation sequencing becomes
      broadly available, especially whole exome sequencing is used in clinical
      diagnosis of the genetic causes of a wide spectrum of intellectual disability,
      autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or
      Rett-like syndrome because of their phenotype but were negative for mutations in
      the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the
      results of the last few years revealed yet 69 different genes. Many of these
      genes are involved in epigenetic gene regulation, chromatin shaping,
      neurotransmitter action or RNA transcription/translation. Genetic data also
      allows to investigate the individual genetic background of an individual patient,
      which can modify the severity of a genetic disorder. SUMMARY: We conclude that
      the Rett syndrome phenotype has a much broader underlying genetic cause and the
      typical phenotype overlap with other genetic disorders. For proper genetic
      counselling, patient perspective and treatment it is important to include both
      phenotype and genetic information.

PMID- 29206689
TI  - Placental fatty acid transfer.
AB  - PURPOSE OF REVIEW: This review outlines recent advances in placental lipid
      transport in relation to maternal metabolic status and pregnancy outcome. A
      particular focus of this review will be on the way these findings may influence
      our understanding of placental transfer of the essential fatty acid
      docosahexaenoic acid (DHA) which is crucial for fetal neurodevelopment and of
      lipid transfer as a predisposing factor for childhood obesity. RECENT FINDINGS:
      Placental metabolism may determine the quantity and composition of fatty acids
      delivered to the fetus. Maternal factors, such as obesity, appear to regulate
      placental lipid metabolism and may influence fatty acids delivery to the fetus.
      Although the role of placental metabolism is now recognized, new evidence also
      suggests important roles for nontraditional fatty acid transporters such as
      Mfsd2a which facilitates transfer of DHA. SUMMARY: Placental lipid metabolism is
      likely to be a determinant of placental transfer of fatty acids to the fetus.
      Maternal conditions, such as obesity, have now been shown to regulate placental
      lipid metabolism and thus may influence fatty acid transfer and fetal
      development. However, it is not yet clear how regulation of placental lipid
      metabolism affects fatty acid delivery to the fetus and its long-term health.

PMID- 29206690
TI  - Mechanisms regulating brain docosahexaenoic acid uptake: what is the recent
      evidence?
AB  - PURPOSE OF REVIEW: To summarize recent advances pertaining to the mechanisms
      regulating brain docosahexaenoic acid (DHA) uptake. DHA is an omega-3
      polyunsaturated fatty acid highly enriched in neuronal membranes and it is
      implicated in several important neurological processes. However, DHA synthesis is
      extremely limited within the brain. RECENT FINDINGS: There are two main plasma
      pools that supply the brain with DHA: the nonesterified pool and the
      lysophosphatidylcholine (lysoPtdCho) pool. Quantitatively, plasma nonesterified
      DHA (NE-DHA) is the main contributor to brain DHA. Fatty acid transport protein 1
      (FATP1) in addition to fatty acid-binding protein 5 (FABP5) are key players that
      regulate brain uptake of NE-DHA. However, the plasma half-life of lysoPtdCho-DHA
      and its brain partition coefficient are higher than those of NE-DHA after
      intravenous administration. SUMMARY: The mechanisms regulating brain DHA uptake
      are more complicated than once believed, but recent advances provide some clarity
      notably by suggesting that FATP1 and FABP5 are key contributors to cellular
      uptake of DHA at the blood-brain barrier. Elucidating how DHA enters the brain is
      important as we might be able to identify methods to better deliver DHA to the
      brain as a potential therapeutic.

PMID- 29206691
TI  - Comprehensive Review of Skiing and Snowboarding Injuries.
AB  - Skiing and snowboarding have increased in popularity since the 1960s. Both sports
      are responsible for a substantial number of musculoskeletal injuries treated
      annually by orthopaedic surgeons. Specific injury patterns and mechanisms
      associated with skiing and snowboarding have been identified. No anatomic
      location is exempt from injury, including the head, spine, pelvis, and upper and
      lower extremities. In these sports, characteristic injury mechanisms often are
      related to the position of the limbs during injury, the athlete's expertise
      level, and equipment design. Controversy exists about the effectiveness of knee
      bracing and wrist guards in reducing the incidence of these injuries.
      Understanding these injury patterns, proper training, and the use of injury
      prevention measures, such as protective equipment, may reduce the overall
      incidence of these potentially debilitating injuries.

PMID- 29206692
TI  - Individualizing the care of older heart failure patients.
AB  - PURPOSE OF REVIEW: The heart failure epidemic is driven mainly by population
      aging and the improving survival of patients with cardiovascular risk factors.
      Aging heart failure patients are affected by multiple concurrent comorbidities
      and geriatric syndromes, the most important of which are frailty and cognitive
      impairment. The purpose of this review is to provide clinicians with practical
      advice on how to individualize the care of older heart failure patients. RECENT
      FINDINGS: Frailty and cognitive impairment are common in older heart failure
      patients. Frailty is increasingly recognized as a key risk factor for functional
      decline, health service utilization and mortality in aging heart failure
      patients. Similarly, cognitive impairment impairs patients' ability for self-care
      and leads to adverse outcomes. Simple and efficient instruments exist to screen
      for these conditions. Heart failure patients who are frail or cognitively
      impaired are best looked after in a disease management setting that is deployed
      in a more integrated healthcare system with access to specialized geriatric
      consultants. Optimal care planning requires knowledge of these conditions as well
      as patient and caregiver engagement. SUMMARY: Frailty and cognitive impairment
      are central features of the heart failure syndrome in aging patients and should
      be routinely considered in assessment and care planning.

PMID- 29206693
TI  - Long-term results of suture annuloplasty for degenerative mitral valve disease: a
      propensity-matched analysis.
AB  - AIMS: Ring annuloplasty is the gold standard of surgical repair in degenerative
      mitral valve disease. However, prosthetic annuloplasty has some drawbacks and
      potential hazards. Suture annuloplasty theoretically is able to preserve annular
      leaflet dynamics and left ventricular performance, but experience is limited. The
      aim of the study was to review the early and long-term outcome of the posterior
      double-suture annuloplasty (DSA) technique for degenerative mitral valve repair.
      METHODS: From January 2002 to December 2008, 400 patients underwent primary
      mitral valve repair for degenerative disease either with posterior DSA [n = 147
      (37%)] or with flexible posterior annuloplasty band [n = 253 (63%)]. Differences
      in patient characteristics were addressed by propensity-score matching (132
      pairs). A composite end-point of mitral valve failure (MVF) was calculated as the
      incidence of mitral valve regurgitation greater than 2+ or need for mitral valve
      replacement at follow-up. RESULTS: After propensity-score matching, the
      distribution of preoperative variables among matched pairs was, on average,
      equal. Isolated annuloplasty and leaflet repair techniques were similarly
      performed in both groups (P = 0.20). In-hospital mortality was comparable between
      the two study groups (P = 0.48). Predischarge echocardiography showed excellent
      results regarding valve hemodynamics (P = 0.71). At a mean follow-up of 11 +/- 3
      years, all-cause mortality (P = 0.12), need for mitral valve replacement (P =
      0.49), and cardiac re-hospitalization rate (P = 0.57) resulted comparable between
      the two groups. Ten-year survival (75 vs. 71%, P = 0.51) and freedom from MVF (92
      vs. 84%, P = 0.39) were similar between posterior annuloplasty band and DSA
      groups. CONCLUSION: Suture annuloplasty demonstrated comparable results with
      posterior flexible band repair and could be a viable option for mitral valve
      surgery in selected patients, such as in the minimally invasive approach, in
      endocarditis, and in developing countries.

PMID- 29206694
TI  - Diagnosis and management of a patient with recurrent variant angina and history
      of percutaneous coronary intervention: vasospasm and percutaneous coronary
      intervention.

PMID- 29206695
TI  - Drug-induced sleep endoscopy: from obscure technique to diagnostic tool for
      assessment of obstructive sleep apnea for surgical interventions.
AB  - PURPOSE OF REVIEW: Provide a practical update on drug-induced sleep endoscopy
      (DISE) for anesthesia providers, which can also serve as a reference for those
      preparing to establish a DISE program. RECENT FINDINGS: New developments in
      surgical approaches to OSA and the growing global incidence of the condition have
      stimulated increased interest and demand for drug-induced sleep endoscopy. New
      techniques include transoral robotic surgery and hypoglossal nerve stimulation.
      Recent DISE literature has sought to address numerous debates including relevance
      of DISE findings to those during physiologic sleep and the most appropriate depth
      and type of sedation for DISE. Propofol and dexmedetomidine have supplanted
      midazolam as the drugs of choice for DISE. Techniques based on pharmacokinetic
      models of propofol are superior to empiric dosing with regard to risk of
      respiratory compromise and the reliability of dexmedetomidine to achieve adequate
      conditions for a complete DISE exam is questionable. SUMMARY: The role of DISE in
      surgical evaluation and planning for treatment of OSA continues to develop.
      Numerous questions as to the optimal anesthetic approach remain unanswered.
      Multicenter studies that employ a standardized approach using EEG assessment,
      pharmacokinetic-pharmacodynamic modelling, and objectively defined clinical
      endpoints will be helpful. There may be benefit to undertaking DISE studies in
      non-OSA patients.

PMID- 29206696
TI  - The perioperative significance of systemic arterial diastolic hypertension in
      adults.
AB  - PURPOSE OF REVIEW: Hypertension affects approximately one third of the U.S.
      population and is the most common preventable medical reason that surgical cases
      are postponed or cancelled. However, subtypes of hypertension and their
      perioperative risks are poorly studied and understood. We will review the natural
      history and pathophysiology of essential hypertension and discuss the
      perioperative significance of diastolic blood pressure elevation. RECENT
      FINDINGS: There is evidence that elevated preoperative diastolic blood pressures
      are associated with an increased perioperative risk of cardiovascular and
      cerebrovascular events and increased postoperatively 30-day mortality. However,
      lower preoperative diastolic blood pressures were found, in one study, to be
      associated with renal injury. SUMMARY: Diastolic hypertension and hypotension
      both carry perioperative risk. Further study needs to be dedicated to elucidating
      the risks and developing strategies for acute and chronic management of diastolic
      blood pressure changes in order to improve perioperative safety.

PMID- 29206697
TI  - Perioperative pulmonary thromboembolism: current concepts and treatment options.
AB  - PURPOSE OF REVIEW: Anesthesiologists are familiar with pulmonary emboli
      prophylaxis paradigms and many have witnessed acute intraoperative embolization.
      Clinicians must balance conservative anticoagulation and aggressive intervention
      in perioperative submassive pulmonary emboli, yet the bulk of the literature
      excludes surgery as a relative contraindication. This review will summarize the
      current treatment options for acute pulmonary emboli, drawing attention to
      special considerations in perioperative submassive pulmonary emboli, and discuss
      right ventricular monitoring to improve assessment of intervention efficacy.
      RECENT FINDINGS: Recent reviews have identified the elevated risk and inadequacy
      of treatment of pulmonary embolism in intra and postoperative patients, in part
      because of the risks of systemic anticoagulation. Early studies of catheter
      directed therapies have shown promising efficacy with a reduction in bleeding
      risk, which is especially important for perioperative patients. Success relies on
      defining endpoints, yet the practice of measuring mean pulmonary artery pressure
      alone to assess intervention efficacy is flawed. SUMMARY: Identifying submassive
      pulmonary emboli that requires treatment and optimizing therapy remains
      difficult. Researchers must consider avoiding systemic anticoagulation and focus
      on designing trials that evaluate intervention efficacy in surgical patients. The
      success of catheter-directed therapy in early trials warrants further
      investigation into using these therapies in the treatment of perioperative
      submassive pulmonary emboli.

PMID- 29206698
TI  - Surgery and discontinuation of angiotensin converting enzyme inhibitors: current
      perspectives.
AB  - PURPOSE OF REVIEW: The current article reviews the current evidence for
      continuing or discontinuing angiotensin-converting enzyme inhibitors (ACEIs) or
      angiotensin receptor blockers (ARBs) during the perioperative period. RECENT
      FINDINGS: In patients undergoing treatment of hypertension with ACEIs or ARBs,
      there are both benefits associated with continuing these medications during the
      perioperative period and higher risk for perioperative hypotension and its
      complications. SUMMARY: Since the introduction of ACEIs and ARBs into clinical
      practice, their use during the perioperative period has been controversial.
      Although these medications increase the risk of serious hypotension immediately
      after induction and maintenance of anesthesia, their use has numerous benefits,
      making it reasonable to continue them during perioperative period.

PMID- 29206699
TI  - Evaluation of antidepressant activity of methanolic extract of Saraca asoca bark
      in a chronic unpredictable mild stress model.
AB  - It is well established that chronic exposure to stressful events plays an
      important role in the etiology of depression. Saraca asoca (Roxb.), De. wild, or
      Saraca indica, belonging to family Fabaceae, is endogenous to India. The flowers,
      seeds, bark, and leaves of the plant have been used widely in Ayurveda medicine.
      The bark extract of S. asoca has shown chemoprotection, myeloprotection, and
      antioxidant potential. Owing to the above-mentioned properties of the plant, the
      present study sought to evaluate the effect of a methanolic extract of S. asoca
      bark in rats exposed to chronic unpredictable mild stress (CUMS) daily for 8
      weeks using a forced-swim test, an open-field test, and a sucrose-preference
      test. The effect of the extract on endogenous antioxidant levels in the brain was
      also assessed using catalase activity, superoxide dismutase activity, reduced
      glutathione levels, and malondialdehyde levels in the brain. Male Sprague-Dawley
      rats received 100 mg/kg (oral) of the extract daily 1 h before daily stress
      exposure for 8 weeks. The extract showed a significant reduction in the
      immobility time in the forced-swim test, increased the total number of line
      crossing, rearing, and grooming in the open-field test, and increased the sucrose
      consumption as well as the levels of endogenous antioxidants significantly in
      comparison with the CUMS control group. Therefore, S. asoca might be a useful
      agent for the treatment or alleviation of symptoms associated with depression
      possibly by reducing CUMS-induced oxidative stress and reactive oxygen species in
      the brain.

PMID- 29206700
TI  - Caregiver anticipatory grief: phenomenology, assessment and clinical
      interventions.
AB  - PURPOSE OF REVIEW: This review aims to synthesize recent findings on anticipatory
      grief in caregivers, referring to its phenomenology, assessment and clinical
      interventions. RECENT FINDINGS: Recent literature illustrates the wide scope of
      the current use of the term anticipatory grief, reflecting caregivers'
      experiences in different end-of-life trajectories. The anticipation of death is
      the distinctive aspect of anticipatory grief in the predeath grief continuum,
      encompassing several progressive losses, past and future. Recently developed
      assessment instruments capture key aspects of this experience, such as separation
      anxiety, anticipation of death and future absence of the person, denial and
      relational losses. Recent findings on prevalence of clinically significant
      predeath symptoms in caregivers range from 12.5 to 38.5%. Beyond personal and
      relational factors, difficult circumstances of end-of-life care significantly
      interfere in adjustment to anticipatory grief. Useful therapeutic interventions
      were identified, such as validation of grief feelings, increased coping and self
      care, anticipation of future losses and reframing roles. However, rigorous
      interventional studies are needed to create guidelines and the manualization of
      specific therapeutic approaches to caregiver anticipatory grief. SUMMARY:
      Findings suggest that anticipatory grief dynamics in different end-of-life
      trajectories should be recognized and adequately assessed. Clinical interventions
      considered useful to support anticipatory grief caregivers are presented, but
      further research is needed to verify effectiveness.

PMID- 29206701
TI  - Thirst in heart failure: what do we know so far?
AB  - PURPOSE OF REVIEW: Thirst is a common and burdensome symptom of heart failure,
      which impacts adversely on quality of life. To date, there is limited research on
      the prevalence of thirst, the factors associated with thirst and interventions to
      help manage thirst in heart failure. This review summarizes key empirical
      research developments of thirst. RECENT FINDINGS: Recent research shows that the
      heart failure syndrome, medications, self-care practice such as fluid restriction
      and anxiety contributes greatly to increased thirst in patients with heart
      failure. In addition, predictors such as being younger, male patient, with high
      symptom burden and serum urea is also associated with thirst. There are no
      intervention studies to manage thirst, only reports of various strategies
      recommended to heart failure patients in clinical practice. SUMMARY: Despite the
      burden of thirst in heart failure patients, strategies to relieve thirst remains
      insufficiently addressed in literature. Further research to improve the
      understanding of the severity of thirst and its relationship to possible factors
      associated with thirst is required in order to develop future interventions to
      either prevent or alleviate troublesome thirst in patients with heart failure.

PMID- 29206702
TI  - Challenges in clarifying goals of care in patients with advanced heart failure.
AB  - PURPOSE OF REVIEW: Patients with advanced heart failure require communication
      about goals of care, yet many challenges exist, leaving it suboptimal. High
      mortality rates and advances in the use of life-sustaining technology further
      complicate communication and underscore the urgency to understand and address
      these challenges. This review highlights current research with a view to
      informing future research and practice to improve goals of care communication.
      RECENT FINDINGS: Clinicians view patient and family barriers as more impactful
      than clinician and system factors in impeding goals of care discussions.
      Knowledge gaps about life-sustaining technology challenge timely goals of care
      discussions. Complex, nurse-led interventions that activate patient, clinician
      and care systems and video-decision aids about life-sustaining technology may
      reduce barriers and facilitate goals of care communication. SUMMARY: Clinicians
      require relational skills in facilitating goals of care communication with
      diverse patients and families with heart failure knowledge gaps, who may be
      experiencing stress and discord. Future research should explore the dynamics of
      goals of care communication in real-time from patient, family and clinician
      perspectives, to inform development of upstream and complex interventions that
      optimize communication. Further testing of interventions is needed in and across
      community and hospital settings.

PMID- 29206703
TI  - Palliative care needs of heart failure patients in China: putting people first.
AB  - PURPOSE OF REVIEW: Recognizing the rising prevalence of heart failure in China,
      patients with heart failure have substantial palliative needs. This review
      highlights recent evidence on the epidemic of heart failure, identifies needs and
      potential benefit of palliative care in heart failure, and sets future strategic
      policy and research directions in China. RECENT FINDINGS: Epidemiological studies
      demonstrate the prevalence of heart failure among women is higher than men in
      China and increases substantially with age. However, few studies have addressed
      the palliative needs of Chinese heart failure patients. The main themes from this
      review include: Healthcare providers should be culturally sensitive whenever
      assessing symptoms and needs. Locally validated, brief outcome measures are
      called for to identify symptoms and needs of Chinese heart failure patients.
      Palliative care should be better integrated into the management of heart failure
      through increased training for healthcare providers, policy development,
      financial support, and cultural acceptance of palliative care. SUMMARY: Large
      scale epidemiological studies are urgently needed to assess the current situation
      of heart failure in China, alongside interventional studies to drive the
      development of innovative palliative care services to address the needs of
      Chinese heart failure patients.

PMID- 29206704
TI  - Palliative care needs assessment in chronic heart failure.
AB  - PURPOSE OF REVIEW: The unmet palliative care needs of patients with chronic heart
      failure (CHF) are well known. Palliative care needs assessment is paramount for
      timely provision of palliative care. The present review provides an overview of
      palliative care needs assessment in patients with CHF: the role of prognostic
      tools, the role of the surprise question, and the role of palliative care needs
      assessment tools. RECENT FINDINGS: Multiple prognostic tools are available, but
      offer little guidance for individual patients. The surprise question is a simple
      tool to create awareness about a limited prognosis, but the reliability in CHF
      seems less than in oncology and further identification and assessment of
      palliative care needs is required. Several tools are available to identify
      palliative care needs. Data about the ability of these tools to facilitate timely
      initiation of palliative care in CHF are lacking. SUMMARY: Several tools are
      available aiming to facilitate timely introduction of palliative care. Focus on
      identification of needs rather than prognosis appears to be more fitting for
      people with CHF. Future studies are needed to explore whether and to what extent
      these tools can help in addressing palliative care needs in CHF in a timely
      manner.

PMID- 29206705
TI  - Institution of Just Culture Physician Peer Review in an Academic Medical Center.
AB  - OBJECTIVES: For academic medical centers to improve quality outcomes,
      identification and optimization of opportunities for improvement are necessary.
      Effective clinical peer review frequently has limitations on timeliness,
      transparency, and consideration of system processes related to untoward clinical
      outcomes. We developed a process to overcome these barriers and capture
      opportunities for process improvement identified within the clinical peer review
      system. METHODS: A multidisciplinary committee was formed to evaluate the current
      process of physician peer review at Magee Womens Hospital of the University of
      Pittsburgh Medical Center. Evaluation of current peer review triggers, processes,
      communication, transparency, and actionable outcomes was performed. A new
      approach was established that incorporated a protected electronic portal to
      improve communication and provider engagement, as well as initiation of a Just
      Culture peer review algorithm to realize opportunities for system improvements.
      RESULTS: The new process has been operative for 2 years. After initiation, the
      average time necessary for full case review decreased by 66% (6-2 months).
      Provider engagement and input have increased to 71%, from less than 10% before
      implementation. Most cases (51%) were identified as having more than one
      causative factor, with systems issues being the most frequent contributor to
      untoward outcomes. CONCLUSIONS: Given the recognized benefits, this approach is
      being considered for implementation on a broader scale within service-line
      quality initiatives across the University of Pittsburgh Medical Center health
      system. Although first implemented among faculty, consideration of incorporation
      into graduate medical education programs is ongoing.

PMID- 29206706
TI  - Quantifying Dental Office-Originating Adverse Events: The Dental Practice Study
      Methods.
AB  - BACKGROUND: Preventable medical errors in hospital settings are the third leading
      cause of deaths in the United States. However, less is known about harm that
      occurs in patients in outpatient settings, where the majority of care is
      delivered. We do not know the likelihood that a patient sitting in a dentist
      chair will experience harm. Additionally, we do not know if patients of certain
      race, age, sex, or socioeconomic status disproportionately experience iatrogenic
      harm. METHODS: We initiated the Dental Practice Study (DPS) with the aim of
      determining the frequency and types of adverse events (AEs) that occur in
      dentistry on the basis of retrospective chart audit. This article discusses the 6
      month pilot phase of the DPS during which we explored the feasibility and
      efficiency of our multistaged review process to detect AEs. RESULTS: At sites 1,
      2, and 3, respectively, 2 reviewers abstracted 21, 11, and 23 probable AEs,
      respectively, from the 100 patient charts audited per site. At site 2, a third
      reviewer audited the same 100 charts and found only 1 additional probable AE. Of
      the total 56 probable AEs (from 300 charts), the expert panel confirmed 9 AE
      cases. This equals 3 AEs per 100 patients per year. Patients who experienced an
      AE tended to be male and older and to have undergone more procedures within the
      study year. CONCLUSIONS: This article presents an overview of the DPS. It
      describes the methods used and summarizes the results of its pilot phase. To
      minimize threats to dental patient safety, a starting point is to understand
      their basic epidemiology, both in terms of their frequency and the extent to
      which they affect different populations.

PMID- 29206707
TI  - Language as Advocacy.

PMID- 29206708
TI  - Use of a Telehealth System to Enhance a Home Exercise Program for a Person With
      Parkinson Disease: A Case Report.
AB  - BACKGROUND AND PURPOSE: This case addresses feasibility of a home-based
      telehealth system to enhance home exercise program (HEP) adherence for a patient
      with Parkinson disease (PD). We describe START-System for Technology-Augmented
      Rehabilitation and Training-and discuss outcomes after integrating START into the
      HEP component of an established therapy protocol, Lee Silverman Voice Technique
      BIG (LSVT BIG). CASE DESCRIPTION: The participant was a 67-year-old woman with PD
      at Hoehn and Yahr Stage II. INTERVENTION: During the first 4 weeks of a 4-month
      intervention, a physical therapist guided the participant through the LSVT BIG
      protocol. START was introduced at week 3; the participant was encouraged to
      complement her daily HEP through the end of the fourth month with START.
      OUTCOMES: Improvements in gait, endurance, balance confidence, and quality of
      life were observed from the start of the assessment to the end of month 1. By
      month 4, the participant maintained or improved with respect to these outcomes.
      Monitored by START, the rate of adherence to her twice-daily HEP prescription was
      24%, but her daily participation rate was 78%. The participant's satisfaction
      with the START system was high, although autonomous feedback provided by START
      was a limiting concern. There were no technical issues or adverse events
      reported. DISCUSSION: This case supports START as a feasible HEP telehealth
      solution for physical therapy, given that increased long-term exercise adherence
      may improve health outcomes for people with PD. The outcomes of this case study
      support further investigation into the use of START for people with PD.Video
      Abstract available for more insights from the authors (see Video; Supplemental
      Digital Content 1, http://links.lww.com/JNPT/A192).

PMID- 29206710
TI  - Academy of Neurologic Physical Therapy 2018 Combined Sections Meeting Platform
      Presentations: Scheduling & Abstracts: (Searchable Platform Abstracts are
      published on-line in PDF format at www.JNPT.org).

PMID- 29206709
TI  - Academy of Neurologic Physical Therapy Programming Combined Sections Meeting
      2018: Tuesday, February 20 to Saturday, February 24, 2018 Preliminary Program
      Schedule.

PMID- 29206711
TI  - Academy of Neurologic Physical Therapy 2018 Combined Sections Meeting Poster
      Presentations: (Searchable Poster Abstracts are published on-line in PDF format
      at www.JNPT.org).

PMID- 29206712
TI  - Call for Academy of Neurologic Physical Therapy Leadership Nominations.

PMID- 29206713
TI  - Educating Future Health Care Professionals About Cybercivility: Needs Assessment
      Study.
AB  - As misbehaviors online in higher education have been widely addressed in recent
      research, the discourse on cyberincivility has become a contemporary issue in
      health professions education. However, studies regarding cybercivility,
      particularly from an interprofessional education standpoint, are few. This study
      assessed the knowledge, experience, and perceptions about cyberincivility among
      students in 4 health care disciplines. Their preferred means of learning about
      cybercivility and the perceived benefits of such education are also discussed.

PMID- 29206714
TI  - Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative
      Breast Cancer.
AB  - PURPOSE: Growth hormone-releasing hormone (GHRH) has been shown to modify the
      growth behavior of many cancers, including breast. GHRH is produced by tumor
      cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH
      receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be
      effectively blocked by synthetic antagonists of its receptor and hence, the
      expression of GHRH-R by tumor cells could serve as a predictor of response to
      GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH
      R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and
      immunophenotypically heterogenous, the staining results were also correlated with
      the histologic subtypes of these tumors. MATERIALS AND METHODS: On the basis of
      histomorphology and immunophenotype, 134 cases of primary TNBCs were further
      subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas
      of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on
      paraffin sections and the staining results were assessed semiquantitatively as
      negative, low expression, moderate, and high expression. RESULTS: Of the 134
      TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8
      as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%)
      of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative
      for GHRH-R and, with the exception of 1 case with low expression, none of the
      metaplastic carcinomas expressed GHRH-R (P<0.005). CONCLUSIONS: A considerable
      number of TNBCs are positive for GHRH-R as a predictor of potential response to
      anti-GHRH-R treatment. This expression however, varies considerably between
      histologic subtypes of triple-negative breast cancers. Although most medullary
      and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST
      show a positive reaction. Testing for GHRH-R expression is therefore advisable if
      anti-GHRH-R therapy is being considered.

PMID- 29206715
TI  - SP174 Antibody Lacks Specificity for NRAS Q61R and Cross-Reacts With HRAS and
      KRAS Q61R Mutant Proteins in Malignant Melanoma.
AB  - HRAS, KRAS, and NRAS, highly homologous proteins, are often mutationally
      activated in cancer. Usually, mutations cluster in codons 12, 13, and 61 and are
      detected by molecular genetic testing of tumor DNA. Recently,
      immunohistochemistry with SP174 antibody has been introduced to detect NRAS Q61R
      mutant protein. Studies on malignant melanomas showed that such an approach could
      be a viable alternative to molecular genetic testing. This investigation was
      undertaken to evaluate the value of SP174 immunohistochemistry for detection of
      NRAS Q61R-mutant isoform. Two hundred ninety-two malignant melanomas were
      evaluated using Leica Bond-Max automated immunostainer. Twenty-nine tumors (10%)
      showed positive immunoreactivity. NRAS codon 61 was polymerase chain reaction
      amplified and sequenced in 24 positive and 92 negative cases using Sanger
      sequencing, quantitative polymerase chain reaction, and next-generation
      sequencing approaches. A c.182A>G substitution leading to NRAS Q61R mutation was
      identified in 22 tumors. Two NRAS wild-type tumors revealed c.182A>G
      substitutions in HRAS and KRAS codon 61, respectively. Both mutations were
      detected by next-generation sequencing and independently confirmed by Sanger
      sequencing. None of 85 NRAS codon 61 wild-type tumors and 7 NRAS mutants other
      than Q61R showed immunoreactivity with SP174 antibody. Thus, SP174 antibody was
      100% sensitive in detecting NRAS Q61R-mutant isoform in malignant melanoma, but
      not fully specific as it cross-reacted with HRAS and KRAS Q61R-mutant proteins.
      Therefore, molecular testing is needed to determine which RAS gene is mutated.
      The rarity of HRAS and KRAS Q61R mutants in malignant melanoma let previous
      investigations erroneously conclude that SP174 is specific for NRAS Q61R-mutant
      protein.

PMID- 29206716
TI  - Primary Epithelioid Angiosarcoma of Finger Masquerading as Epithelioid
      Hemangioma: Report of a Case and Analysis of Mutational Pattern in Epithelioid
      Hemangiomas and Angiosarcomas by Next-generation Sequencing.
AB  - AIMS: We report an unusual case of epithelioid angiosarcoma (AS) mimicking an
      epithelioid hemangioma (EH) and analyze mutational patterns in EHs and ASs.
      METHODS AND RESULTS: A 58-year-old woman presented with a finger lump and
      metastatic lung nodules. Initial needle biopsies showed an EH, with only focal
      atypical histologic features. The patient underwent finger amputation and
      resection of lung nodules. The amputation specimen and lung nodules revealed
      features of AS. Fluorescence in situ hybridization for FOS and FOSB gene
      rearrangements were negative in the primary tumor as well as in the lung
      metastasis. Intrigued by the unique morphologic features of an AS masquerading as
      an EH, we expanded our study by analyzing mutations in EHs versus ASs using a
      targeted next-generation sequencing of 50 cancer-related genes. Seven EHs and 6
      ASs including the present case were subjected to mutation analysis using the Ion
      AmpliSeq Cancer Hotspot Panel v2 assay of 50 cancer-related genes. The present
      case lacked mutation. Novel somatic variants were detected in 2 of 7 EHs and 1 of
      6 ASs. Sorting intolerant from tolerant and polymorphism phenotyping analysis
      revealed benign/tolerated and deleterious variants in both tumor types.
      Deleterious variants TP53 c.707T>C (p.Tyr236Cys), FLT3 c.1995C>T (p.Met665Ile),
      and SMO c.1919C>T (p.Thr640Ile) were detected in EH, while AS revealed
      deleterious variant PTPN11 c.226G>A (p.Glu76Lys). CONCLUSIONS: We present an
      epithelioid AS mimicking EH. We report novel somatic variants in EHs and AS.
      Benign variants may not be associated with development of these tumors. Whereas,
      deleterious variants, especially PTPN11 c.226G>A, may be linked to tumorigenesis
      of AS.

PMID- 29206717
TI  - Targets and Receptor of Sexual Transmission of Zika Virus.

PMID- 29206718
TI  - Imaging of Exudative Age-Related Macular Degeneration: Toward a Shift in the
      Diagnostic Paradigm?

PMID- 29206719
TI  - Trends in Urodynamic Procedures, Surgical Procedures, and Overall Health Resource
      Utilization in the Adult Taiwanese Population With Urinary Incontinence: A
      Secondary Data Analysis.
AB  - BACKGROUND: The prevalence and incidence of the main risk factors for urinary
      incontinence (UI) have both increased over time. In addition, official statistics
      indicate that Taiwan is on course to evolve from an aging society into an aged
      society within the next decade. However, most of the studies in the literature
      that address the natural history of UI target Western and other non-Asian
      populations. Taiwan lacks knowledge of the natural history of UI. PURPOSE: The
      aims of this research were to study the trends in the use of urodynamic and
      surgical procedures for various subtypes of UI and to investigate the
      relationship between UI and healthcare resource utilization. METHODS: The data on
      1 million, randomly selected people who were enrolled in the Taiwan National
      Health Insurance program between 2000 and 2008 were extracted from the
      Longitudinal Health Insurance Database. The population and all procedures were
      identified based on the International Classification of Disease, Ninth Revision,
      Clinical Modification codes. Annual incidence of UI was calculated on an annual
      basis, and trend analysis was performed using logistic regression models. The
      association between UI and healthcare utilization was examined using generalized
      linear models in a gamma distribution with a log link function. RESULTS: Overall,
      the trend in the annual incidence for all types of UI increased significantly (p
      < .01). Significantly increasing trends in the use of urodynamic procedures over
      time were observed for mixed and other types of UI (p < .01). In addition, a
      significantly increasing trend was observed in the annual rates of surgical
      procedures that were received by patients with urge or stress UI (p < .05).
      Patients with UI showed significantly higher healthcare resource utilization,
      including number of ambulatory visits, number of hospitalizations, average
      ambulatory care expenditures, and average days of hospitalization, than those
      without UI. However, limited information is available on the conservative
      treatment of UI in the database. CONCLUSIONS: UI symptoms may lead to increased
      healthcare resource utilization in patients with UI.

PMID- 29206720
TI  - Recruitment of Female Sex Workers in HIV Prevention Trials: Can Efficacy
      Endpoints Be Reached More Efficiently?
AB  - BACKGROUND/SETTING: Randomized controlled trials (RCTs) of HIV biomedical
      prevention interventions often enroll participants with varying levels of HIV
      exposure, including people never exposed to HIV. We assessed whether enrolling
      larger proportion of participants with consistently high exposure to HIV, such as
      female sex workers (FSWs), might reduce trial duration and improve the accuracy
      of product efficacy estimates in future HIV prevention trials. METHODS: We used
      an individual-based stochastic model to simulate event-driven RCTs of an HIV
      prevention intervention providing 80% reduction in susceptibility per act under
      different proportions of FSW enrolled. A 5% annual dropout rate was assumed for
      both FSW and non-FSW in our main scenario, but rates of up to 50% for FSW were
      also explored. RESULTS: Enrolling 20% and 50% FSW reduced the median-simulated
      trial duration from 30 months with 0% FSW enrolled to 22 months and 17 months,
      respectively. Estimated efficacy increased from 71% for RCTs without FSW to 74%
      and 76% for RCTs with 20% and 50% FSW enrolled, respectively. Increasing the FSW
      dropout rate to 50% increased the duration of RCTs by 1-2 months on average and
      preserved the gain in estimated efficacy. CONCLUSIONS: Despite the potential
      logistical challenges of recruiting and retaining FSW, trialists should revisit
      the idea of enrolling FSW in settings where HIV incidence among FSW is higher
      than among non-FSW. Our analysis suggests that enrolling FSW would increase HIV
      incidence, reduce trial duration, and improve efficacy estimates, even if the
      annual dropout rate among FSW participants is high.

PMID- 29206721
TI  - Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled
      Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir.
AB  - BACKGROUND: Fostemsavir is a prodrug of temsavir, an attachment inhibitor that
      binds to HIV-1 gp120, blocking viral attachment to host CD4 T-cells. The phase 2b
      trial AI438011 investigated the safety, efficacy, and dose-response of
      fostemsavir vs ritonavir-boosted atazanavir (ATV/r) in treatment-experienced, HIV
      1-infected subjects. METHODS: Two hundred fifty-one treatment-experienced
      subjects with baseline (BL) susceptibility to study drugs [temsavir half-maximal
      inhibitory concentration (IC50) <100 nM, PhenoSense Entry assay] received
      fostemsavir or ATV/r, each with tenofovir disoproxil fumarate + raltegravir.
      Subjects meeting resistance-testing criteria were assessed for emergent viral
      drug resistance. Changes in temsavir IC50 from BL was given a conservative
      technical cutoff (>3-fold increase). RESULTS: 66/200 fostemsavir and 14/51 ATV/r
      subjects had resistance testing performed; 44/66 and 9/14 were successfully
      tested using the PhenoSense GT assay. No subjects had emergent tenofovir
      disoproxil fumarate or ATV resistance. Six fostemsavir-treated subjects developed
      emergent raltegravir resistance. 29/66 fostemsavir-treated subjects had an
      evaluable phenotype using PhenoSense Entry (which tests for viral susceptibility
      to temsavir) and 13/29 exhibited >3-fold increase in temsavir IC50 from BL. gp120
      population sequencing was successful in 11/13 subjects and 7 had emergent
      substitutions in gp120 associated with reduced temsavir susceptibility (S375,
      M426, or M434). However, 5/13 fostemsavir-treated subjects achieved subsequent
      suppression to <50 copies/mL before the week 48 database lock, regardless of key
      gp120 substitutions. CONCLUSIONS: Response rates remained similar across study
      arms regardless of BL nucleoside reverse transcriptase inhibitor, nonnucleoside
      reverse transcriptase inhibitor, and protease inhibitor resistance-associated
      mutations. Emergent changes in viral susceptibility occurred more frequently with
      fostemsavir compared with ATV/r. However, the full impact of temsavir IC50
      changes and emergent HIV-1 gp120 substitutions, and thus appropriate clinical
      cutoffs, requires further study. Fostemsavir is being evaluated in a phase 3
      trial in heavily treatment-experienced subjects.

PMID- 29206722
TI  - Rapid Serological Tests Ineffectively Screen for HIV Exposure in HIV-Positive
      Infants.
AB  - BACKGROUND: Data on the performance and utility of rapid serological tests in
      infants to determine HIV exposure are unclear and in some instances
      contradictory. This study sought to understand the performance of rapid
      serological tests in high HIV burden, high Option B+ coverage settings to be used
      as an HIV exposure screening tool. METHODS: A total of 3600 infants up to 24
      months of age at 4 regional hospitals in Uganda were systematically enrolled and
      tested simultaneously using both HIV rapid serological and nucleic acid-based
      tests. RESULTS: Only 58 of the 94 HIV-positive infants who received both rapid
      serological and nucleic acid-based tests were positive with the rapid serological
      test (sensitivity: 61.7%; 95% confidence interval: 51.1 to 71.5). Using rapid
      serological tests to screen infants for exposure to HIV and follow-up nucleic
      acid-based testing would have missed 38.3% (36 of 94) of HIV-positive infants.
      Finally, several HIV-positive infants who were negative by rapid serological test
      presented to well-child entry points and were considered healthy. All 3 HIV
      positive infants presenting to outreach and immunization were negative by rapid
      serological testing and 73% (8 of 11) presenting to outpatient. CONCLUSIONS:
      These data suggest that the use of rapid serological tests may have inadequate
      performance as an indicator of exposure and potential HIV infection among infants
      presenting at both well-child (immunization and community outreach) and sick
      infant (nutrition and inpatient) entry points. To improve the identification of
      HIV-positive infants, nucleic acid-based testing should instead be considered in
      infants aged younger than 18 months.

PMID- 29206723
TI  - Brief Report: Assessing the Association Between Changing NRTIs When Initiating
      Second-Line ART and Treatment Outcomes.
AB  - BACKGROUND: After first-line antiretroviral therapy failure, the importance of
      change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is
      uncertain due to the high potency of protease inhibitors used in second line.
      SETTING: We used clinical data from 6290 adult patients in South Africa and
      Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
      Southern Africa cohort. METHODS: We included patients who initiated on standard
      first-line antiretroviral therapy and had evidence of first-line failure. We used
      propensity score-adjusted Cox proportional-hazards models to evaluate the impact
      of change in NRTI on second-line failure compared with remaining on the same NRTI
      in second line. In South Africa, where viral load monitoring was available,
      treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In
      Zambia, it was defined as 2 consecutive CD4 counts <100 cells/mm. RESULTS: Among
      patients in South Africa initiated on zidovudine (AZT), the adjusted hazard ratio
      for second-line virologic failure was 0.25 (95% confidence interval: 0.11 to
      0.57) for those switching to tenofovir (TDF) vs. remaining on AZT. Among patients
      in South Africa initiated on TDF, switching to AZT in second line was associated
      with reduced second-line failure (adjusted hazard ratio = 0.35 [95% confidence
      interval: 0.13 to 0.96]). In Zambia, where viral load monitoring was not
      available, results were less conclusive. CONCLUSIONS: Changing NRTI in second
      line was associated with better clinical outcomes in South Africa. Additional
      clinical trial research regarding second-line NRTI choices for patients initiated
      on TDF or with contraindications to specific NRTIs is needed.

PMID- 29206725
TI  - Time of Day When Type 1 Diabetes Patients With Eating Disorder Symptoms Most
      Commonly Restrict Insulin.
AB  - OBJECTIVE: Restricting insulin to lose weight is a significant problem in the
      clinical management of type 1 diabetes (T1D). Little is known about this behavior
      or how to effectively intervene. Identifying when insulin restriction occurs
      could allow clinicians to target typical high-risk times or formulate hypotheses
      regarding factors that influence this behavior. The current study investigated
      the frequency of insulin restriction by time of day. METHODS: Fifty-nine adults
      with T1D and eating disorder symptoms completed 72 hours of real-time reporting
      of eating and insulin dosing with continuous glucose monitoring. We used a
      generalized estimating equation model to test the global hypothesis that
      frequency of insulin restriction (defined as not taking enough insulin to cover
      food consumed) varied by time of day, and examined frequency of insulin
      restriction by hour. We also examined whether patterns of insulin restriction for
      72 hours corresponded with patients' interview reports of insulin restriction for
      the past 28 days. RESULTS: Frequency of insulin restriction varied as a function
      of time (p = .016). Insulin restriction was the least likely in the morning hours
      (6:00-8:59 AM), averaging 6% of the meals/snacks consumed. Insulin restriction
      was more common in the late afternoon (3:00-5:59 PM), peaking at 29%. Insulin was
      restricted for 32% of the meals/snacks eaten overnight (excluding for
      hypoglycemia); however, overnight eating was rare. Insulin restriction was
      associated with higher 120-minute postprandial blood glucose (difference = 44.4
      mg/dL, 95% confidence interval = 22.7-68.5, p < .001) and overall poorer
      metabolic control (r = 0.43-0.62, p's < .01). Patients reported restricting
      insulin for a greater percentage of meals and snacks for the past 28 days than
      during the 72 hour real-time assessment; however, the reports were correlated
      (Spearman's rho = 0.46, p < .001) and accounted for similar variance in HbA1c
      (34% versus 35%, respectively). CONCLUSIONS: Findings suggest that insulin
      restriction may be less likely in the morning, and that late afternoon is a
      potentially important time for additional therapeutic support. Results also
      suggest that systematic clinical assessment and treatment of overnight eating
      might improve T1D management.

PMID- 29206726
TI  - Standardization of Pediatric Interfacility Transport Handover: Measuring the
      Development of a Shared Mental Model.
AB  - OBJECTIVES: To determine if standardization of pediatric interfacility transport
      handover is associated with the development of a prototypical shared mental model
      between healthcare providers. DESIGN: A single center, prepost, retrospective
      cohort study. SETTINGS: A 259-bed, tertiary care, pediatric referral center.
      PATIENTS: Children 0 to 18 years old transferred to our critical care units or
      emergency center from October 2016 to February 2017. INTERVENTIONS:
      Standardization of interfacility handover using a multidisciplinary checklist,
      didactic teaching, and simulation conducted midway through the study period.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was a shared mental model
      index defined as percent congruence among handover participants regarding key
      patient healthcare data including patient identification, diagnoses, transport
      interventions, immediate postadmission care plans, and anticipatory guidance for
      ongoing care. Secondary outcomes were handover comprehensiveness and teaming
      metrics such as efficiency, attendance, interruption frequency, and team member
      inclusion. During the study period, 100 transport handovers were observed of
      which 50 were preintervention and 50 post. A majority of handovers represented
      transfers to the emergency center (41%) or PICU (45%). There were no observable
      differences between prepost intervention cohorts by general characteristics,
      admission diagnoses, or severity of illness metrics including Pediatric Index of
      Mortality-3-Risk of Mortality, length of stay, mortality, frequency of invasive
      and noninvasive ventilation, and vasoactive use. The shared mental model index
      increased from 38% to 78% following standardization of handover. Attendance (76%
      vs 94%), punctuality (91.5% vs 98%), attention (82% vs 92%), summarization (42%
      vs 72%), and provision of anticipatory guidance (42% vs 58%) also improved.
      Efficiency was unchanged with a mean handover duration of 4 minutes in both
      cohorts. CONCLUSIONS: Considerable enhancements in handover quality, team
      participation, and the development of a shared mental model after standardization
      of interfacility transport handover were noted. These findings were achieved
      without compromising handover efficiency.

PMID- 29206724
TI  - Impact of Racial Discrimination and Hostility on Adrenergic Receptor
      Responsiveness in African American Adults.
AB  - OBJECTIVE: Racial discrimination is increasingly recognized as a contributor to
      increased cardiovascular disease (CVD) risk among African Americans. Previous
      research has shown significant overlap between racial discrimination and
      hostility, an established predictor of CVD risk including alterations in
      adrenergic receptor functioning. The present study examined the associations of
      racial discrimination and hostility with adrenergic receptor responsiveness.
      METHODS: In a sample (N = 57) of young to middle-aged African American adults
      (51% female) with normal and mildly elevated blood pressure, a standardized
      isoproterenol sensitivity test (CD25) was used to evaluate beta-AR
      responsiveness, whereas the dose of phenylephrine required to increase mean
      arterial pressure by 25 mm Hg (PD25) was used to assess alpha1-AR responsiveness.
      Racial discrimination was measured using the Perceived Racism Scale and hostility
      was assessed using the Cook-Medley Hostility Scale. RESULTS: In hierarchical
      regression models, greater racial discrimination, but not hostility, emerged as a
      significant predictor of decreased beta-adrenergic receptor responsiveness (beta
      = .38, p = .004). However, moderation analysis revealed that the association
      between racial discrimination and blunted beta-adrenergic receptor responsiveness
      was strongest among those with higher hostility (beta = .49, 95% confidence
      interval = .17-.82, p = .004). In addition, hostility, but not racial
      discrimination, significantly predicted alpha1-AR responsiveness. CONCLUSIONS:
      These findings suggest racial discrimination was associated with blunted beta
      adrenergic receptor responsiveness, providing further evidence of the potential
      contribution of racial discrimination to increased CVD risk among African
      Americans. The adverse effects of discrimination on cardiovascular health may be
      enhanced in individuals with higher levels of hostility.

PMID- 29206727
TI  - Assessment of Myocardial Function and Injury by Echocardiography and Cardiac
      Biomarkers in African Children With Severe Plasmodium falciparum Malaria.
AB  - OBJECTIVES: Perturbed hemodynamic function complicates severe malaria. The Fluid
      Expansion as Supportive Therapy trial demonstrated that fluid resuscitation,
      involving children with severe malaria, was associated with increased mortality,
      primarily due to cardiovascular collapse, suggesting that myocardial dysfunction
      may have a role. The aim of this study was to characterize cardiac function in
      children with severe malaria. DESIGN: A prospective observational study with
      clinical, laboratory, and echocardiographic data collected at presentation (T0)
      and 24 hours (T1) in children with severe malaria. Cardiac index and ejection
      fraction were calculated at T0 and T1. Cardiac troponin I and brain natriuretic
      peptide were measured at T0. We compared clinical and echocardiographic variables
      in children with and without severe malarial anemia (hemoglobin < 5 mg/dL) at T0
      and T1. SETTING: Mbale Regional Referral Hospital. PATIENTS: Children 3 months to
      12 years old with severe falciparum malaria. INTERVENTIONS: Usual care.
      MEASUREMENTS AND MAIN RESULTS: We enrolled 104 children, median age 23.3 months,
      including 61 children with severe malarial anemia. Cardiac troponin I levels were
      elevated (> 0.1 ng/mL) in n equals to 50, (48%), and median brain natriuretic
      peptide was within normal range (69.1 pg/mL; interquartile range, 48.4-90.8). At
      T0, median Cardiac index was significantly higher in the severe malarial anemia
      versus nonsevere malarial anemia group (6.89 vs 5.28 L/min/m) (p = 0.001), which
      normalized in both groups at T1 (5.60 vs 5.13 L/min/m) (p = 0.452). Cardiac index
      negatively correlated with hemoglobin, r equals to -0.380 (p < 0.001). Four
      patients (3.8%) had evidence of depressed cardiac systolic function (ejection
      fraction < 45%). Overall, six children died, none developed pulmonary edema,
      biventricular failure, or required diuretic treatment. CONCLUSIONS: Elevation of
      cardiac index, due to increased stroke volume, in severe malaria is a physiologic
      response to circulatory compromise and correlates with anemia. Following whole
      blood transfusion and antimalarial therapy, cardiac index in severe malarial
      anemia returns to normal. The majority (> 96%) of children with severe malaria
      have preserved myocardial systolic function. Although there is evidence for
      myocardial injury (elevated cardiac troponin I), this does not correlate with
      cardiac dysfunction.

PMID- 29206728
TI  - Distributions and Behavior of Vital Signs in Critically Ill Children by Admission
      Diagnosis.
AB  - OBJECTIVES: Define the distributions of heart rate and intraarterial blood
      pressure in children at admission to an ICU based on admission diagnosis and
      examine trends in these physiologic signs over 72 hours from admission (or to
      discharge if earlier). DESIGN: A retrospective analysis of continuously acquired
      signals. SETTING: A quaternary and primary referral children's hospital with a
      general PICU and cardiac critical care unit. PATIENTS: One thousand two hundred
      eighty-nine patients less than 18 years old were analyzed. Data from individual
      patient admissions were divided into 19 groups by primary admission diagnosis or
      surgical procedure. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS:
      Distributions at admission are dependent on patient age and admission diagnosis
      (p < 10). Heart rate decreases over time, whereas arterial blood pressure is
      relatively stable, with differences seen in the directions and magnitude of these
      trends when analyzed by diagnosis group (p < 10). Multiple linear regression
      analysis shows that patient age, diagnosis group, and physiologic vital sign
      value at admission explain 50-63% of the variation observed for that physiologic
      signal at 72 hours (or at discharge if earlier) with admission value having the
      greatest influence. Furthermore, the variance of either heart rate or arterial
      blood pressure for the individual patient is smaller than the variance measured
      at the level of the group of patients with the same diagnosis. CONCLUSIONS: This
      is the first study reporting distributions of continuously measured physiologic
      variables and trends in their behavior according to admission diagnosis in
      critically ill children. Differences detected between and within diagnostic
      groups may aid in earlier recognition of outliers as well as allowing refinement
      of patient monitoring strategies.

PMID- 29206730
TI  - Understanding the Impact of Fluid Restriction on Growth Outcomes in Infants
      Following Cardiac Surgery.
AB  - OBJECTIVE: Fluid restriction is reported to be a barrier in providing adequate
      nutrition following cardiac surgery. The specific aim of this study was to
      evaluate the adequacy of nutritional intake during the postoperative period using
      anthropometrics by comparing preoperative weight status, as measured by weight
      for-age z scores, to weight status at discharge home. DESIGN: Prospective cohort
      study. SETTING: Cardiac ICU at Miami Children's Hospital. PATIENTS: Infants from
      birth to 12 months old who were scheduled for cardiac surgery at Miami Children's
      Hospital between December 2013 and September 2014 were followed during the
      postoperative stay. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN
      RESULTS: Preoperative and discharge weight-for-age z scores were analyzed. The
      Risk Adjustment for Congenital Heart Surgery 1 categories were obtained to
      account for the individual complexity of each case. In patients who had
      preoperative and discharge weights available (n = 40), the mean preoperative
      weight-for-age z score was -1.3 +/- 1.43 and the mean weight-for-age z score at
      hospital discharge was -1.89 +/- 1.35 with a mean difference of 0.58 +/- 0.5 (p <
      0.001). A higher Risk Adjustment for Congenital Heart Surgery 1 category was
      correlated with a greater decrease in weight-for-age z scores (r = -0.597; p =
      0.002). CONCLUSIONS: Nutritional status during the postoperative period was found
      inadequate through the use of objective anthropometric measures and by comparing
      them with normal growth curves. Increase in surgical risk categories predicted a
      greater decrease in weight-for-age z scores. The development of future protocols
      for nutritional intervention should consider surgical risk categories.

PMID- 29206729
TI  - Extracorporeal Cardiopulmonary Resuscitation in the Pediatric Cardiac Population:
      In Search of a Standard of Care.
AB  - OBJECTIVES: Although clinical and pharmacologic guidelines exist for the practice
      of cardiopulmonary resuscitation in children (Pediatric Advanced Life Support),
      the practice of extracorporeal cardiopulmonary resuscitation in pediatric cardiac
      patients remains without universally accepted standards. We aim to explore
      variation in extracorporeal cardiopulmonary resuscitation procedures by surveying
      clinicians who care for this high-risk patient population. DESIGN: A 28-item
      cross-sectional survey was distributed via a web-based platform to clinicians
      focusing on cardiopulmonary resuscitation practices and extracorporeal membrane
      oxygenation team dynamics immediately prior to extracorporeal membrane
      oxygenation cannulation. SETTINGS: Pediatric hospitals providing extracorporeal
      mechanical support services to patients with congenital and/or acquired heart
      disease. SUBJECTS: Critical care/cardiology specialist physicians, cardiothoracic
      surgeons, advanced practice nurse practitioners, respiratory therapists, and
      extracorporeal membrane oxygenation specialists. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Survey web links were distributed over a 2-month
      period with critical care and/or cardiology physicians comprising the majority of
      respondents (75%). Nearly all respondents practice at academic/teaching
      institutions (97%), 89% were from U.S./Canadian institutions and 56% reported
      less than 10 years of clinical experience. During extracorporeal cardiopulmonary
      resuscitation, a majority of respondents reported adherence to guideline
      recommendations for epinephrine bolus dosing (64%). Conversely, 19% reported
      using only one to three epinephrine bolus doses regardless of extracorporeal
      cardiopulmonary resuscitation duration. Inotropic support is held after
      extracorporeal membrane oxygenation cannulation "most of the time" by 58% of
      respondents and 94% report using afterload reducing/antihypertensive agents
      "some" to "most of the time" after achieving full extracorporeal membrane
      oxygenation support. Interruptions in chest compressions are common during active
      cannulation according to 77% of respondents. CONCLUSIONS: The results of this
      survey identify wide variability in resuscitative practices during extracorporeal
      cardiopulmonary resuscitation in the pediatric cardiac population. The deviations
      from established Pediatric Advanced Life Support CPR guidelines support a call
      for further inquiry into the pharmacologic and logistical care surrounding
      extracorporeal cardiopulmonary resuscitation.

PMID- 29206732
TI  - Enteral Feeding in Children on Noninvasive Ventilation Is Feasible, but
      Clinicians Remain Fearful.

PMID- 29206731
TI  - Enteral Feeding Practices in Infants With Congenital Heart Disease Across
      European PICUs: A European Society of Pediatric and Neonatal Intensive Care
      Survey.
AB  - OBJECTIVES: To describe enteral feeding practices in pre and postoperative
      infants with congenital heart disease in European PICUs. DESIGN: Cross-sectional
      electronic survey. SETTING: European PICUs that admit infants with congenital
      heart disease pre- and postoperatively. PARTICIPANTS: One senior PICU physician
      or designated person per unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Fifty-nine PICUs from 18 European countries responded to the survey.
      PICU physicians were involved in the nutritional care of children with congenital
      heart disease in most (76%) PICUs, but less than 60% of units had a dedicated
      dietician. Infants with congenital heart disease were routinely fed
      preoperatively in only 63% of the PICUs, due to ongoing concerns around
      prostaglandin E1 infusion, the presence of umbilical venous and/or arterial
      catheters, and the use of vasoactive drugs. In three quarters of the PICUs (76%),
      infants were routinely fed during the first 24 hours postoperatively. Units
      cited, the most common feeding method, both pre and postoperatively, was
      intermittent bolus feeds via the gastric route. Importantly, 69% of European
      PICUs still did not have written guidelines for feeding, but this varied for pre
      and postoperative patients. CONCLUSIONS: Wide variations in practices exist in
      the nutritional care between European PICUs, which reflects the absence of local
      protocols and scientific society-endorsed guidelines. This is likely to
      contribute to suboptimal energy delivery in this particularly vulnerable group.

PMID- 29206733
TI  - Is the ICU a Risk Factor for Future Asthma Readmissions?

PMID- 29206734
TI  - Viral Bronchiolitis in PICUs: Looking Further Than the Acute Phase!

PMID- 29206735
TI  - The Most Vulnerable SPROUTs: Severe Sepsis in the Pediatric Hematopoietic Cell
      Transplantation Population.

PMID- 29206736
TI  - Fluid Overload and Extracorporeal Membrane Oxygenation: Is Renal Replacement
      Therapy a Buoy or an Anchor?

PMID- 29206737
TI  - Piperacillin-Tazobactam Plus Vancomycin Equals Acute Kidney Injury: Does It Add
      Up?

PMID- 29206738
TI  - Communication of Risk and Benefit.

PMID- 29206739
TI  - The Quest to Preserve Muscle Mass-Lessons From Pediatric Burn Injury.

PMID- 29206740
TI  - Healthcare in the PICU May Be More Complicated Than We Thought-Who Knew?

PMID- 29206741
TI  - Assessing Cardiac Surgery-Associated Acute Kidney Injury in Pediatric Patients.

PMID- 29206742
TI  - The authors reply.

PMID- 29206743
TI  - Can Serum Neutrophil Gelatinase-Associated Lipocalin Be Precisely Used as a
      Diagnostic Marker of Sepsis in Pediatric Cases?

PMID- 29206744
TI  - Detectable Concentrations of Inhaled Tobramycin in Critically Ill Children
      Without Cystic Fibrosis: Should Routine Monitoring Be Recommended?
AB  - OBJECTIVES: To determine the percentage of detectable tobramycin troughs and
      acute kidney injury in critically ill children without cystic fibrosis on inhaled
      therapy. DESIGN: Historic cohort. SETTING: Academic hospital. PATIENTS: Forty
      children less than 18 years receiving inhaled tobramycin across 6.5 years.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary objective was to
      determine the percentage of detectable tobramycin troughs greater than or equal
      to 0.5 ug/mL. Secondary objectives included a comparison of acute kidney injury
      in children with and without detectable troughs. Twenty-two (55%) had trough
      concentrations obtained. Ten of these (45.5%) had detectable concentrations, with
      a median of 0.85 ug/mL (interquartile range, 0.5-2.0). There was no statistical
      significance between the detectable and nondetectable groups in age, gender, and
      method of administration. However, patients in the detectable group tended to be
      younger than nondetectable group and more likely to have a tracheotomy. There was
      a clinically significant decrease in estimated glomerular filtration rate in the
      detectable trough group. CONCLUSIONS: Detectable troughs were noted in almost
      half of patients with concentrations obtained. A clinically significant decrease
      in estimated glomerular filtration rate was noted in patients with detectable
      concentrations. Continued work should be directed to better understand outcomes
      and monitoring in children requiring inhaled tobramycin.

PMID- 29206745
TI  - Cardiosphere-Derived Cells and Ischemic Heart Failure.
AB  - After a myocardial infarction, heart tissue becomes irreversibly damaged, leading
      to scar formation and inevitably ischemic heart failure. Of the many available
      interventions after a myocardial infarction, such as percutaneous intervention or
      pharmacological optimization, none can reverse the ischemic insult on the heart
      and restore cardiac function. Thus, the only available cure for patients with
      scarred myocardium is allogeneic heart transplantation, which comes with
      extensive costs, risks, and complications. However, multiple studies have shown
      that the heart is, in fact, not an end-stage organ and that there are endogenous
      mechanisms in place that have the potential to spark regeneration. Stem cell
      therapy has emerged as a potential tool to tap into and activate this endogenous
      framework. Particularly promising are stem cells derived from cardiac tissue
      itself, referred to as cardiosphere-derived cells (CDCs). CDCs can be extracted
      and isolated from the patient's myocardium and then administered by
      intramyocardial injection or intracoronary infusion. After early success in the
      animal model, multiple clinical trials have demonstrated the safety and efficacy
      of autologous CDC therapy in humans. Clinical trials with allogeneic CDCs showed
      early promising results and pose a potential "off-the-shelf" therapy for patients
      in the acute setting after a myocardial infarction. The mechanism responsible for
      CDC-induced cardiac regeneration seems to be a combination of triggering native
      cardiomyocyte proliferation and recruitment of endogenous progenitor cells, which
      most prominently occurs via paracrine effects. A further understanding of the
      mediators involved in paracrine signaling can help with the development of a stem
      cell-free therapy, with all the benefits and none of the associated
      complications.

PMID- 29206746
TI  - Mitral Valve and Subvalvular Repair for Secondary Mitral Regurgitation: Rationale
      and Clinical Outcomes of the Papillary Muscle Sling.
AB  - Secondary mitral regurgitation (MR) is a common finding in patients with dilated
      cardiomyopathy, and it is associated with poor outcomes. It is the result of
      incomplete systolic closure of the mitral valve (MV) as a consequence of left
      ventricular dilatation, papillary muscle displacement with impaired systolic
      shortening, and mitral leaflet tethering. MV surgery may be performed in cases of
      significant secondary MR despite guideline-directed medical therapy. However, MV
      repair, which is most commonly performed with an undersized ring annuloplasty, is
      associated with a 30-60% recurrence of moderate or greater MR at mid-term follow
      up. To improve MV repair durability, several adjunctive subvalvular procedures
      have been proposed, one of which is the addition of papillary muscle
      approximation utilizing a papillary muscle sling. Recent studies comparing the
      outcomes of a conventional undersized ring annuloplasty with a MV repair
      utilizing a papillary muscle sling have reported a significant reduction in
      recurrent moderate or severe MR, greater left ventricular reverse remodeling, and
      improved MV apparatus geometry with the addition of the papillary muscle sling.
      We present a comprehensive review of the pathophysiology of secondary MR, and the
      rationale and clinical outcomes of MV repair with papillary muscle sling
      placement for the treatment of secondary MR.

PMID- 29206747
TI  - Safety and Efficacy of Atazanavir Powder and Ritonavir in HIV-1-Infected Infants
      and Children From 3 Months to <11 Years of Age: The PRINCE-2 Study.
AB  - BACKGROUND: Novel antiretroviral formulations that are palatable, safe, and
      effective are needed for infants and children. METHODS: PRINCE-2 is an ongoing
      clinical trial assessing safety, efficacy, and palatability of once-daily
      atazanavir powder formulation boosted with ritonavir (ATV + RTV) plus optimized
      dual nucleos(t)ide reverse transcriptase inhibitors therapy in antiretroviral
      naive/experienced children with screening HIV-1 RNA >=1000 copies/mL. Children 3
      months to <11 years received ATV + RTV by 5 baseline weight bands: 5 to <10 kg =
      150/80 mg; 5 to <10 kg = 200/80 mg; 10 to <15 kg = 200/80 mg; 15 to <25 kg =
      250/80 mg; and 25 to <35 kg = 300/100 mg. RESULTS: Of 99 treated children, 83.8%
      and 59.6% remained on ATV powder until 24 and 48 weeks, respectively. Through 48
      weeks, the most common adverse events were upper respiratory tract infections
      (33.3%), gastroenteritis (28.3%), vomiting (21.2%) and hyperbilirubinemia (18.2%;
      none leading to treatment discontinuation). Serious adverse events occurred in
      20.2% of patients. Laboratory grade 3-4 hyperbilirubinemia occurred in 9.2% and
      elevated total/pancreatic amylase in 33.7%/3.1%. At week 24, proportions with
      virologic suppression (HIV-1 RNA <50 copies/mL; intention-to-treat analysis)
      across weight bands were 10/23 (43.5%), 2/12 (16.5%), 10/21 (47.6%), 19/35
      (54.3%) and 5/8 (62.5%), respectively. Virologic suppression was similar in
      antiretroviral-naive/experienced patients and lowest in the 5 to <10 kg = 200/80
      mg group, likely because of higher baseline HIV-1 RNA and discontinuation
      (66.7%). Overall, virologic suppression at weeks 24 (46.5%) and 48 (43.0%) was
      comparable. At week 48, 83.3% and 74.1% of caregivers reported no trouble giving
      ATV powder and RTV, respectively. CONCLUSIONS: ATV powder palatability, efficacy
      and lack of unexpected safety findings support its use for HIV-1-infected
      children >=3 months to <11 years.

PMID- 29206748
TI  - Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected Children
      Treated With Atazanavir Powder and Ritonavir: Combined Analysis of the PRINCE-1
      and -2 Studies.
AB  - BACKGROUND: Two clinical studies (PRINCE-1 and -2) in HIV-1-infected children
      assessed the safety, efficacy and pharmacokinetics of dual nucleos(t)ide reverse
      transcriptase inhibitor background therapy plus once-daily atazanavir (ATV)
      powder formulation boosted with ritonavir (ATV + RTV). Here, we present a
      combined analysis of ATV pharmacokinetics and pharmacodynamics across these
      studies. METHODS: Intensive 24-hour pharmacokinetic profiles at steady state
      compared ATV exposures (area under the concentration-time curve in one dosing
      interval) in 5 ATV + RTV baseline weight-band dosing categories, with historic
      data in adults receiving ATV + RTV 300/100 mg capsules. Repeated ATV Ctrough
      measurements over 48 weeks explored relationships between ATV composite Ctrough
      quartiles (CCQs) with virologic efficacy and key safety parameters. RESULTS: Of
      146 children included in this combined analysis, 49.3% were male, 56.8% were
      Black/African American and 62.3% were antiretroviral experienced. Proportions
      with HIV-1 RNA <50 copies/mL at week 48 were 13/32, 24/32, 19/32 and 13/28 in the
      lowest through highest ATV CCQs, respectively. Mean changes from baseline in
      total bilirubin at week 48 were +0.3, +0.5, +0.6 and +1.0 mg/dL in the lowest
      through highest ATV CCQs, respectively. Corresponding proportions with adverse
      events of hyperbilirubinemia by week 48 were 1/36, 4/36, 5/36 and 13/35,
      respectively. Changes from baseline in total amylase or electrocardiogram
      parameters and adverse events of diarrhea did not vary by ATV CCQs. CONCLUSIONS:
      Weight-band dosing of ATV + RTV plus optimized dual nucleos(t)ide reverse
      transcriptase inhibitors in young HIV-1-infected children achieved similar ATV
      exposure to that in adults; no unexpected safety findings occurred, and with the
      exception of lower virologic suppression in the lowest ATV CCQ, there was no
      apparent trend in virologic suppression across ATV CCQs.

PMID- 29206749
TI  - A California Infant With Insidious Left Wrist Swelling.

PMID- 29206750
TI  - Ceftazidime-Avibactam Antimicrobial Activity and Spectrum When Tested Against
      Gram-negative Organisms From Pediatric Patients: Results From the INFORM
      Surveillance Program (United States, 2011-2015).
AB  - BACKGROUND: Ceftazidime-avibactam was approved by the US Food and Drug
      Administration in 2015 to treat complicated intra-abdominal and urinary tract
      infections in adults and is under clinical development for treating pediatric
      patients. METHODS: Among 53,381 Gram-negative organisms (1 per patient) collected
      in 2011-2015, 8461 (15.9%) were from pediatric (<=17 years old) patients. The
      isolates were collected from 82 US medical centers and susceptibility tested
      against ceftazidime-avibactam (avibactam at fixed 4 MUg/mL) and comparators by
      reference broth microdilution methods. Susceptibility results were stratified by
      patient age: <=1 (3671 isolates); 2-5 (1900); 6-12 (1644) and 13-17 years old
      (1246). Enterobacteriaceae with an extended-spectrum beta-lactamase (ESBL)
      screening-positive phenotype were evaluated by microarray-based assay for genes
      encoding ESBLs, KPC, NDM and transferable AmpC enzymes. RESULTS: Ceftazidime
      avibactam inhibited >99.9% of all Enterobacteriaceae at the <=8 MUg/mL
      susceptible break point and was highly active against ESBL screening-positive
      phenotype Escherichia coli and Klebsiella pneumoniae. Overall, 83.6% of ESBL
      screening-positive phenotype K. pneumoniae were susceptible to meropenem. Only 1
      of 4724 Enterobacteriaceae (0.02%) isolates was nonsusceptible to ceftazidime
      avibactam, an Enterobacter aerogenes with a ceftazidime-avibactam minimum
      inhibitory concentration (MIC) value of 16 MUg/mL and negative results for all
      beta-lactamase tested. Ceftazidime-avibactam was very active against Pseudomonas
      aeruginosa (MIC50/90, 1/4 MUg/mL; 99.1% susceptible), including isolates
      nonsusceptible to meropenem (94.0% susceptible to ceftazidime-avibactam) or
      piperacillin-tazobactam (91.7% susceptible) or ceftazidime (89.6% susceptible).
      Ceftazidime-avibactam activity against P. aeruginosa did not vary substantially
      among age groups (98.8%-99.3% susceptible) or year of isolation (98.5%-100.0%
      susceptible). CONCLUSIONS: Ceftazidime-avibactam was very active against a large
      collection of Gram-negative bacilli isolated from pediatric patients, including
      P. aeruginosa and Enterobacteriaceae with an ESBL screening-positive phenotype
      and resistant to carbapenems.

PMID- 29206751
TI  - The Impact of Clostridium difficile Infection on Mortality in Patients With
      Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND AIMS: Clostridium difficile infection (CDI) has been associated
      with an increased mortality risk among patients with inflammatory bowel disease
      (IBD) in multiple observational studies. We performed a systematic review and
      meta-analysis to help clearly define the magnitude of risk in IBD patients with
      and without CDI, and to assess the risk in individual IBD subtypes. METHODS: A
      systematic search of multiple electronic databases was conducted for
      observational studies reporting the risk of mortality in IBD, stratified by the
      presence of CDI. Weighted summary estimates were calculated using generalized
      inverse variance with random-effects model. Study quality was assessed using the
      Newcastle-Ottawa scale. RESULTS: Ten observational studies were identified (8
      from North America and 2 from Europe) and included 40,700 IBD patients with CDI
      and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a
      higher risk of mortality compared with IBD patients without CDI [odds ratios
      (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I=93%]. The results were
      stable in high-quality studies and in hospitalized patients. When patients were
      stratified by IBD type, CDI was associated with increased mortality in patients
      with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I), but not in
      patients with Crohn's disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I).
      Individual studies were limited by an inability to control for IBD disease
      activity and therapeutic interventions. CONCLUSIONS: On the basis of 10
      observational studies with at least moderate quality, CDI seems to increase
      mortality risk in IBD, particularly in ulcerative colitis. These findings are a
      cause for concern and suggest that CDI should be managed aggressively in patients
      with IBD.

PMID- 29206752
TI  - Rather than Surgical Technique, Dedicated Stroke Centers Improve Bowel and Life
      Outcomes in Acute Mesenteric Ischemia.

PMID- 29206753
TI  - The Effects of Sleep on the Commensal Microbiota: Eyes Wide Open?
AB  - Sleep dysfunction is an epidemic, the implications of which have a profound
      impact on a variety of gastrointestinal disease. Recent data suggests a
      relationship between sleep dysfunction and intestinal dysbiosis, a known
      proinflammatory driver. This article evaluates the interplay between sleep
      dysfunction and gastrointestinal health and disease, with a focus on the impact
      of circadian rhythm disruption on the commensal microbiota.

PMID- 29206754
TI  - Abdominal Ultrasound Does Not Reveal Significant Alterations in Patients With
      Nonceliac Wheat Sensitivity.
AB  - GOALS: The goal of this study was (A) to evaluate abdominal ultrasound signs in
      nonceliac wheat sensitivity (NCWS) patients for features useful in diagnosis and
      (B) to compare these aspects with those of celiac patients to assess whether
      ultrasound can be useful in the differential diagnosis between NCWS and celiac
      disease (CD). BACKGROUND: NCWS diagnosis is difficult as no biomarkers of this
      condition have as yet been identified. In CD ultrasound aspects have been
      identified that have a good diagnostic accuracy. STUDY: We prospectively
      recruited 45 NCWS patients (11 males, 34 females; mean age 35.7 y). Three control
      groups were included: (A) 99 age-matched CD patients; (B) 18 patients with
      seronegative CD; (C) 50 patients with irritable bowel syndrome (IBS) who did not
      improve on a wheat-free diet. NCWS diagnosis was confirmed on the basis of an
      elimination diet and double-blind placebo-controlled (DBPC) challenge. Ultrasound
      sign investigation included: dilatation of the small bowel loops, thickening of
      the small bowel wall, hyperperistalsis, enlarged mesenteric lymph nodes, ascites,
      hyposplenism, altered diameter of the portal vein. RESULTS: NCWS patients showed
      a low frequency of pathologic ultrasound findings. Dilated or thickened loops
      appeared more often in CD patients than in NCWS patients (88.8% vs. 20%;
      P<0.0001). These US signs were significantly more frequent in seronegative CD
      than in NCWS patients (both P<0.0001), whereas no difference was found between
      NCWS patients and IBS controls. CONCLUSIONS: In NCWS patients' ultrasound does
      not show a characteristic pattern which could be helpful for diagnosis. However,
      US can be useful to differentiate between NCWS and CD patients and especially
      those with seronegative CD. (ClinicalTrials.gov NCT03017274).

PMID- 29206755
TI  - THE OASIS MP-1 SUBSTUDY: Characterization of the Effect of Ocriplasmin on
      Microperimetry Parameters.
AB  - PURPOSE: To evaluate the effects of ocriplasmin and symptomatic vitreomacular
      adhesion resolution on visual fixation and macular sensitivity using
      microperimetry. METHODS: MP-1 parameters were analyzed from 3 OASIS sites after
      the use of standardized instruments and testing procedures over 24 months.
      RESULTS: A total of 27 patients (19 ocriplasmin, 8 sham) were evaluated. Mean
      distance of the preferred fixation locus to the anatomical center was farther in
      the sham group at baseline and farther in the sham versus ocriplasmin group
      throughout the study. Retinal sensitivity values were consistently higher in the
      ocriplasmin versus sham group after Month 3. Fewer patients in the ocriplasmin
      group had predominantly eccentric fixation at study end compared with the sham
      group, which also had an increased number of patients with unstable fixation.
      Patients with vitreomacular adhesion resolution had lower bivariate contour area,
      fewer relative scotomas, and higher retinal sensitivity parameters at baseline
      than those with unresolved vitreomacular adhesion. CONCLUSION: Substudy results
      suggest that fixation and sensitivity parameters tended to be better in the
      ocriplasmin group than in the sham group over time. The substudy identified
      parameters that were distinct between patients with and without vitreomacular
      adhesion resolution, suggesting that microperimetry warrants further study as a
      relevant biomarker for visual function.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- 29206756
TI  - Optical Coherence Tomography Angiography Before and After Bevacizumab Injection
      in Ocular Ischemic Syndrome.

PMID- 29206757
TI  - CONTACT VERSUS NONCONTACT WIDE-FIELD VIEWING SYSTEMS: Why Not Have the Best of
      Both Worlds?

PMID- 29206758
TI  - EARLY MICROVASCULAR AND NEURAL CHANGES IN PATIENTS WITH TYPE 1 AND TYPE 2
      DIABETES MELLITUS WITHOUT CLINICAL SIGNS OF DIABETIC RETINOPATHY.
AB  - PURPOSE: To assess and compare early modifications in inner retinal layer
      thickness and optical coherence tomography angiography parameters in patients
      with diabetes mellitus (DM) Types 1 and 2 without clinical signs of diabetic
      retinopathy. METHODS: Ninety eyes of 90 subjects (24 Type 1 DM, 36 Type 2 DM, and
      30 healthy controls) were prospectively evaluated with spectral domain OCT, swept
      source OCT angiography, and color fundus photography (on the same day). Retinal
      nerve fiber layer, ganglion cell layer (GCL+), and nerve fiber layer + GCL+
      (GCL++) thickness were automatically determined by the instrument in the 1, 3,
      and 6 central mm. On OCT angiography, the following parameters were evaluated:
      area of foveal avascular zone, number of focally dilated endings of the
      capillaries (detected only on OCT angiography), presence of regular/irregular
      foveal avascular zone, capillary loss, and capillary network irregularities in
      the superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS:
      Ganglion cell layer+ (P = 0.0099) and GCL++ (P = 0.0367) were significantly
      thicker in DM Type 1 versus DM Type 2 in 1 central mm, after adjustment for age
      and DM duration. The area of foveal avascular zone was significantly larger in DM
      Type 1 versus controls in both SCP and DCP and in DM Type 1 versus Type 2 only in
      DCP (P < 0.05 for all); the number of focally dilated endings of the capillaries
      was higher in DM Type 1 versus controls in both SCP and DCP (P < 0.01 for all);
      and in DM Type 2 versus controls only in DCP (P = 0.007). Perifoveal capillary
      loss in SCP and inner retinal layer thickness had the highest correlation in both
      DM types. CONCLUSION: There are specific neural and microvascular modifications
      even before clinical signs of diabetic retinopathy in DM Types 1 and 2.
      Perifoveal capillary loss in the SCP is highly correlated with inner retinal
      layer. These data may help in characterization of patients at the preclinical
      stage of diabetic retinopathy.

PMID- 29206759
TI  - MULTIMODAL IMAGING OF CHOROIDAL LESIONS IN DISSEMINATED MYCOBACTERIUM CHIMAERA
      INFECTION AFTER CARDIOTHORACIC SURGERY.
AB  - PURPOSE: To explore morphologic characteristics of choroidal lesions in patients
      with disseminated Mycobacterium chimaera infection subsequent to open-heart
      surgery. METHODS: Nine patients (18 eyes) with systemic M. chimaera infection
      were reviewed. Activity of choroidal lesions were evaluated using biomicroscopy,
      fundus autofluorescence, enhanced depth imaging optical coherence tomography,
      fluorescein angiography/indocyanine green angiography, and optical coherence
      tomography angiography. Relationships of choroidal findings to systemic disease
      activity were sought. RESULTS: All 9 male patients, aged between 49 and 66 years,
      were diagnosed with endocarditis and/or aortic graft infection. Mean follow-up
      was 17.6 months. Four patients had only inactive lesions (mild disease). In all
      five patients (10 eyes) with progressive ocular disease, indocyanine green
      angiography was superior to other tests for revealing new lesions and active
      lesions correlated with hyporeflective choroidal areas on enhanced depth imaging
      optical coherence tomography. One eye with a large choroidal granuloma developed
      choroidal neovascularization. Optical coherence tomography angiography showed
      areas with reduced perfusion at the inner choroid. All 5 patients with
      progressive ocular disease had evidence of systemic disease activity within +/-6
      weeks' duration. CONCLUSION: Choroidal manifestation of disseminated M. chimaera
      infection indicates systemic disease activity. Multimodal imaging is suitable to
      recognize progressive ocular disease. We propose ophthalmologic screening
      examinations for patients with M. chimaera infection.

PMID- 29206760
TI  - Development of Noninvasive in Vivo Approach to Assess Vascular Permeability in
      Inflammation Using Fluorescence Imaging.
AB  - INTRODUCTION: In vivo fluorescence imaging can quantify vascular permeability
      without requiring sacrifice of animals. However, use of this noninvasive approach
      for vascular permeability assessment in remote organ injury caused by systemic
      inflammatory disease has not been reported. METHODS: Evans blue (EB) and Genhance
      750 fluorescent dye were mixed and injected into mice. The lung as a remote organ
      and the footpad as a noninvasive observational site were assessed in a cecal
      ligation and puncture (CLP)-induced systemic inflammation mouse model and
      compared with sham and hydrocortisone pretreated (CLP + HC) mouse models.
      Extraction of EB in harvested tissues was assessed as a conventional indicator of
      vascular permeability. Fluorescent intensities in the footpad or harvested lung
      were assessed and their correlation was analyzed to investigate this novel,
      noninvasive approach for estimation of lung vascular permeability. RESULTS:
      Fluorescent intensity in the footpad and harvested lung in the CLP group was
      significantly higher than in the other groups (footpad, sham vs. CLP, P < 0.0001;
      CLP vs. CLP + HC, P = 0.0004; sham vs. CLP + HC, P = 0.058; lung, sham vs. CLP, P
      < 0.0001; CLP vs. CLP + HC, P < 0.0001; sham vs. CLP + HC, P = 0.060). The
      fluorescent intensity in the footpad was strongly correlated with that in the
      lung (r = 0.95). CONCLUSIONS: This fluorescent technique may be useful for
      vascular permeability assessment based on EB quantification. Footpad fluorescent
      intensity was strongly correlated with that in the lung, and may be a suitable
      indicator in noninvasive estimation of lung vascular permeability.

PMID- 29206762
TI  - Soluble Epoxide Hydrolase Plays a Vital Role in Angiotensin II-Induced Lung
      Injury in Mice.
AB  - BACKGROUND: Angiotensin II plays a vital role in the pathogenesis of acute
      respiratory distress syndrome (ARDS). However, its mechanism is not well defined.
      Angiotensin II upregulates the expression of soluble epoxide hydrolase (sEH;
      Ephx2). sEH is suggested as a potential pharmacologic target for ARDS. The
      present study investigates whether the sEH is involved in the angiotensin II
      triggered pulmonary inflammation and edema using an angiotensin II-induced lung
      injury animal model. METHODS: Lung injury was induced by angiotensin II
      intratracheally instillation in wild-type or Ephx2 deficient mice. RESULTS: sEH
      activities were markedly increased in wild-type mice treated with angiotensin II.
      Angiotensin II markedly increased the levels of tumor necrosis factor-alpha and
      interleukin-1beta in bronchoalveolar lavage fluid, worsened alveolar capillary
      protein leak and lung histological alterations, and elevated activity of
      activator protein-1 and nuclear factor-kappaB. However, these changes were
      significantly improved in Ephx2 deficient mice. Moreover, Losartan, an
      angiotensin II receptor 1 antagonist, abolished the sEH induction and improved
      mortality. CONCLUSIONS: Angiotensin II-induced lung injury was improved in sEH
      gene deleted mice. The angiotensin II-triggered pulmonary inflammation is
      mediated, at least in part, through the sEH.

PMID- 29206761
TI  - Skeletal Muscle Mitochondrial Function is Determined by Burn Severity, Sex, and
      Sepsis, and is Associated With Glucose Metabolism and Functional Capacity in
      Burned Children.
AB  - BACKGROUND: Restoring normal mitochondrial function represents a new target for
      strategies aimed at mitigating the stress response to severe burn trauma and
      hastening recovery. Our objective was to investigate the determinants of skeletal
      muscle mitochondrial respiratory capacity and function and its association with
      glucose metabolism and functional capacity in burned children. METHODS: Data from
      burned children enrolled in the placebo arm of an ongoing prospective clinical
      trial were analyzed. Mitochondrial respiratory capacity was determined in
      permeabilized myofibers by high-resolution respirometry on at least one occasion
      per participant. In subsets of patients, glucose kinetics and cardiorespiratory
      fitness (VO2peak) were also determined. Mixed multiple regression models were
      used to identify the determinants of mitochondrial respiratory function and to
      assess the relationship between mitochondrial respiration and both glucose
      control and functional capacity (VO2peak). MAIN RESULTS: Increasing full
      thickness burn size was associated with greater adjusted coupled (ATP-producing)
      respiration, adjusted for age, sex, sepsis, and time of testing (P < 0.01; n =
      55, obs = 97). Girls had on average 23.3% lower coupled respiration (adjusted
      mean and 95% confidence of interval [CI], -7.1; -12.6 to -1.7 pmol/s/mg; P <
      0.025) and 29.8% lower respiratory control than boys (adjusted mean and 95% CI, 
      0.66; -1.07 to -0.25; P < 0.01; n = 55, obs = 97). The presence of sepsis was
      associated with lower respiration coupled to ATP production by an average of
      25.5% compared with nonsepsis (adjusted mean and 95% CI, -6.9; -13.0 to -0.7
      pmol/s/mg; P < 0.05; n = 55, obs = 97), after adjustment for age, sex, full
      thickness burn size, and time of testing. During a hyperinsulinemic euglycemic
      clamp, hepatic glucose release was associated with greater coupled respiration
      and respiratory control (P < 0.05; n = 42, obs = 73), independent of age, sepsis,
      full-thickness burn size, and time postinjury testing. Coupled respiration was
      positively associated with VO2peak after adjustment for age, full-thickness burn
      size, and time of exercise testing (P < 0.025; n = 18, obs = 25). CONCLUSIONS:
      Burn severity, sex, and sepsis influence skeletal muscle mitochondrial function
      in burned children. Glucose control and functional capacity are associated with
      altered mitochondrial respiratory function in muscle of burn survivors,
      highlighting the relationship of altered muscle bioenergetics with the clinical
      sequelae accompanying severe burn trauma.

PMID- 29206764
TI  - PET-CT in Critically Ill Patients: Diagnosing the Unsuspected.
AB  - OBJECTIVE: Quick identification of septic source is fundamental in patients with
      severe sepsis of unknown origin. The purpose of this case report was to assess
      the benefit and feasibility of an early PET-CT in critically ill patients with
      undiagnosed sepsis. DATA SOURCES: Clinical observations of two patients. STUDY
      SELECTION: Case reports. DATA EXTRACTION: Data extracted from medical records,
      after patient's consent. Illustrations were collected from the imaging software.
      DATA SYNTHESIS: We admitted two critically ill patients for suspected sepsis and
      altered mental state. As all bacteriological samples were initially sterile,
      diagnostic workups in both patients led us to suspect underlying malignant
      hemopathy. In fact, the lumbar puncture of the first patient revealed a large B
      cell lymphoma, and an acquired thrombotic thrombocytopenic purpura was suspected
      in the second patient. However, PET-CTs performed in both patients displayed
      infra-clinical underlying infectious foci. Within 48 hours, both patients
      developed a clearly identified sepsis linked to the described focus, and
      favorable outcome thanks to the precious information delivered by the PET-CT.
      CONCLUSIONS: PET-CT precisely detected the deep foci of infection about 48 hours
      prior to the diagnosis of sepsis. The cases reports suggested the use of this
      image technique in ICU for patients with sepsis of unknown origin.

PMID- 29206763
TI  - Association of Clinical Hypoperfusion Variables With Lactate Clearance and
      Hospital Mortality.
AB  - BACKGROUND: Lactate has shown utility in assessing the prognosis of patients
      admitted to the hospital with confirmed or suspected shock. Some findings of the
      physical examination may replace it as screening tool. We have determined the
      correlation and association between clinical perfusion parameters and lactate at
      the time of admission; the correlation between the change in clinical parameters
      and lactate clearance after 6 and 24 h of resuscitation; and the association
      between clinical parameters, lactate, and mortality. METHODS: Prospective cohort
      study of adult patients hospitalized in the emergency room with infection,
      polytrauma, or other causes of hypotension. We measured serum lactate, capillary
      refill time, shock index, and pulse pressure at 0, 6, and 24 h after admission. A
      Spearman's correlation was performed between clinical variables and lactate
      levels, as well as between changes in clinical parameters and lactate clearance.
      The operative characteristics of these variables were determined by area under
      the receiver operating characteristic curve analysis and the association between
      lactate, clinical variables, and mortality through logistic regression. RESULTS:
      A total of 1,320 patients met the inclusion criteria, 66.7% (n = 880) confirmed
      infection, 19% (n = 251) polytrauma, and 14.3% (n = 189) another etiology. No
      significant correlation was found between any clinical variable and lactate
      values (r < 0.28). None of the variable had an adequate discriminatory capacity
      to detect hyperlactatemia (AUC < 0.62). In the multivariate model, lactate value
      at admission was the only variable independently associated with mortality (OR
      1.2; 95% CI = 1.1-1.1). CONCLUSIONS: Among patients with hypoperfusion risk or
      shock, no correlation was found between clinical variables and lactate. Of the
      set of parameters collected, lactate at admission was the only independent marker
      of mortality.

PMID- 29206765
TI  - The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model
      for Sepsis.
AB  - OBJECTIVES: In accordance with Rory's Regulations, hospitals across New York
      State developed and implemented protocols for sepsis recognition and treatment to
      reduce variations in evidence informed care and preventable mortality. The New
      York Department of Health sought to develop a risk assessment model for accurate
      and standardized hospital mortality comparisons of adult septic patients across
      institutions using case-mix adjustment. DESIGN: Retrospective evaluation of
      prospectively collected data. PATIENTS: Data from 43,204 severe sepsis and septic
      shock patients from 179 hospitals across New York State were evaluated. SETTINGS:
      Prospective data were submitted to a database from January 1, 2015, to December
      31, 2015. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Maximum likelihood
      logistic regression was used to estimate model coefficients used in the New York
      State risk model. The mortality probability was estimated using a logistic
      regression model. Variables to be included in the model were determined as part
      of the model-building process. Interactions between variables were included if
      they made clinical sense and if their p values were less than 0.05. Model
      development used a random sample of 90% of available patients and was validated
      using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were
      considerably greater than 0.05, suggesting good calibration. Areas under the
      receiver operator curve in the developmental and validation subsets were 0.770
      (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating
      good discrimination. Development and validation datasets had similar
      distributions of estimated mortality probabilities. Mortality increased with
      rising age, comorbidities, and lactate. CONCLUSIONS: The New York Sepsis Severity
      Score accurately estimated the probability of hospital mortality in severe sepsis
      and septic shock patients. It performed well with respect to calibration and
      discrimination. This sepsis-specific model provides an accurate, comprehensive
      method for standardized mortality comparison of adult patients with severe sepsis
      and septic shock.

PMID- 29206767
TI  - Prevention of Ventilator-Associated and Early Postoperative Pneumonia Through
      Tapered Endotracheal Tube Cuffs: A Systematic Review and Meta-Analysis of
      Randomized Controlled Trials.
AB  - OBJECTIVE: Microaspiration of subglottic secretions is considered a major
      pathogenic mechanism of hospital-acquired pneumonia, either early postoperative
      or ventilator-associated pneumonia. Tapered endotracheal tube cuffs have been
      proposed to provide a better seal of the extraluminal airway, thereby preventing
      microaspiration and possibly hospital-acquired pneumonia. We performed a
      systematic review and meta-analysis to assess the value of endotracheal tubes
      with tapered cuffs in the prevention of hospital-acquired pneumonia. DATA
      SOURCES: A systematic search of MEDLINE, EMBASE, CENTRAL/CCTR,
      ClinicalTrials.gov, and ICTRP was conducted up to March 2017. STUDY SELECTION:
      Eligible trials were randomized controlled clinical trials comparing the impact
      of tapered cuffs versus standard cuffs on hospital-acquired pneumonia. DATA
      EXTRACTION: Random-effects meta-analysis calculated odds ratio and 95% CI for
      hospital-acquired pneumonia occurrence rate between groups. Secondary outcome
      measures included mortality, duration of mechanical ventilation, length of
      hospital and ICU stay, and cuff underinflation. DATA SYNTHESIS: Six randomized
      controlled clinical trials with 1,324 patients from intensive care and
      postoperative wards were included. Only two studies concomitantly applied
      subglottic secretion drainage, and no trial performed continuous cuff pressure
      monitoring. No significant difference in hospital-acquired pneumonia incidence
      per patient was found when tapered cuffs were compared with standard cuffs (odds
      ratio, 0.97; 95% CI, [0.73-1.28]; p = 0.81). There were likewise no differences
      in secondary outcomes. CONCLUSIONS: Application of tapered endotracheal tube
      cuffs did not reduce hospital-acquired pneumonia incidence among ICU and
      postoperative patients. Further research should examine the impact of concomitant
      use of tapered cuffs with continuous cuff pressure monitoring and subglottic
      secretion drainage.

PMID- 29206766
TI  - Hospital Variation in Renal Replacement Therapy for Sepsis in the United States.
AB  - OBJECTIVES: Acute renal replacement therapy in patients with sepsis has increased
      dramatically with substantial costs. However, the extent of variability in use
      across hospitals-and whether greater use is associated with better outcomes-is
      unknown. DESIGN: Retrospective cohort study. SETTING: Nationwide Inpatient Sample
      in 2011. PATIENTS: Eighteen years old and older with sepsis and acute kidney
      injury admitted to hospitals sampled by the Nationwide Inpatient Sample in 2011.
      INTERVENTIONS: We estimated the risk- and reliability-adjusted rate of acute
      renal replacement therapy use for patients with sepsis and acute kidney injury at
      each hospital. We examined the association between hospital-specific renal
      replacement therapy rate and in-hospital mortality and hospital costs after
      adjusting for patient and hospital characteristics. MEASUREMENTS AND MAIN
      RESULTS: We identified 293,899 hospitalizations with sepsis and acute kidney
      injury at 440 hospitals, of which 6.4% (n = 18,885) received renal replacement
      therapy. After risk and reliability adjustment, the median hospital renal
      replacement therapy rate for patients with sepsis and acute kidney injury was
      3.6% (interquartile range, 2.9-4.5%). However, hospitals in the top quintile of
      renal replacement therapy use had rates ranging from 4.8% to 13.4%. There was no
      significant association between hospital-specific renal replacement therapy rate
      and in-hospital mortality (odds ratio per 1% increase in renal replacement
      therapy rate: 1.03; 95% CI, 0.99-1.07; p = 0.10). Hospital costs were
      significantly higher with increasing renal replacement therapy rates (absolute
      cost increase per 1% increase in renal replacement therapy rate: $1,316; 95% CI,
      $157-$2,475; p = 0.03). CONCLUSIONS: Use of renal replacement therapy in sepsis
      varied widely among nationally sampled hospitals without associated differences
      in mortality. Improving renal replacement standards for the initiation of therapy
      for sepsis may reduce healthcare costs without increasing mortality.

PMID- 29206768
TI  - Inhibition of Group Ia Afferents Between Brachioradialis and Flexor Carpi
      Radialis in Humans: A Study Using an Electromyogram-Averaging Method.
AB  - PURPOSE: Our previous studies using a poststimulus time histogram method
      demonstrated inhibitory spinal reflex arcs (inhibition) between the
      brachioradialis (BR) and flexor carpi radialis (FCR) in humans. Group I afferents
      mediated the inhibition through an oligosynaptic path. In this study, effects of
      the inhibition on excitability of the motoneuron pools were examined, and we
      tried to clarify which afferents of group Ia or Ib are responsible for the
      inhibition. METHODS: We evaluated the effects of low-threshold afferents between
      BR and FCR on FCR and BR motoneuron pools, respectively, using an electromyogram
      averaging method in 14 healthy human subjects. Changes of rectified and averaged
      electromyogram of BR by electrical conditioning stimulation with the intensity
      below the motor threshold to the median nerve branch innervating FCR (FCR nerve)
      and those of FCR by the stimulation to the radial nerve branch innervating BR (BR
      nerve) were evaluated. RESULTS: The stimulation to the FCR and BR nerves produced
      an early and significant trough of rectified and averaged electromyogram of BR
      and FCR, respectively, in all the subjects. The amount of inhibition of BR and
      FCR was 13.2 +/- 3.4% (mean +/- SD) and 14.2 +/- 1.4%, respectively. The trough
      of BR and FCR diminished by tonic vibration stimuli to a respective FCR and BR.
      Such a trough was never provoked by cutaneous stimulation. CONCLUSIONS: The
      inhibition between BR and FCR depresses excitability of the FCR and BR motoneuron
      pools, respectively. Group Ia afferents should mediate the inhibition.

PMID- 29206769
TI  - Severe menopausal symptoms associated with reduced adherence to antiretroviral
      therapy among perimenopausal and menopausal women living with HIV in Metro
      Vancouver.
AB  - OBJECTIVES: Although more women living with HIV (WLWH) are entering midlife, the
      experiences of perimenopausal and menopausal WLWH, including the effects of
      menopausal symptoms severity, remain understudied. This study longitudinally
      investigated the correlates of antiretroviral therapy (ART) adherence among
      perimenopausal and menopausal WLWH from Metro Vancouver. METHODS: Analyses drew
      on longitudinal data (2014-2017) from Sexual health and HIV/AIDS: Women's
      Longitudinal Needs Assessment, an ongoing community-based cohort of WLWH, aged
      14+, from Metro Vancouver, Canada. At baseline and biannually, participants
      completed an interviewer-administered questionnaire. Bivariate and multivariable
      logistic regression with generalized estimating equations were used to identify
      the correlates of self-reported <95% ART adherence. RESULTS: The sample included
      109 perimenopausal and menopausal WLWH (233 observations), with a median age of
      49 years (IQR 44-53). Whereas most (68.8%) participants experienced menopausal
      symptoms, only 17% had received treatment (eg, antidepressants, hormone therapy)
      at baseline. In multivariable analysis, severe menopausal symptoms (adjusted odds
      ratio [AOR] 1.03, 95% confidence interval [CI] 1.00-1.06), injection drug use
      (AOR 2.86, 95% CI 1.44-5.55), and physical/sexual violence (AOR 2.33, 95% CI 1.02
      5.26) independently and positively correlated with <95% adherence. CONCLUSIONS:
      These findings suggest that menopausal symptoms may undermine ART adherence, with
      overlapping vulnerabilities such as injection drug use and sexual/physical
      violence further exacerbating poor ART adherence. Women-centred, trauma-informed
      care approaches to detect menopause and treat menopausal symptoms are urgently
      needed. Such approaches should holistically address the intersecting barriers to
      adherence and link WLWH to peripheral health and social services, including
      trauma counseling and evidence-based harm reduction services.

PMID- 29206770
TI  - The cross-sectional association between chemerin and bone health in peri/pre and
      postmenopausal women: results from the EPIC-Potsdam study.
AB  - OBJECTIVE: Recent in vitro data suggested that the novel adipokine chemerin may
      influence bone health. However, only limited evidence of the relationship between
      chemerin and bone health in humans is available. Therefore, this study aimed to
      investigate the association between chemerin and broadband ultrasound attenuation
      (BUA) in peri/premenopausal and postmenopausal women. METHODS: Data from the
      German population-based European Prospective Investigation into Cancer and
      Nutrition-Potsdam cohort comprising 404 peri/premenopausal and 279 postmenopausal
      women were analyzed. Multivariable-adjusted analysis of covariance including age,
      body mass index, waist circumference, smoking status, education, physical
      activity, alcohol consumption, and hormone use was used to investigate potential
      relationships between the adipokine and BUA levels in peri/premenopausal and
      postmenopausal women, respectively. RESULTS: The concentrations of chemerin were
      lower in peri/premenopausal women (median 118.0 ng/mL, interquartile range [IQR]
      99.2-135.0), compared with postmenopausal women (median 140.0 ng/mL, IQR 121.0
      167.0). In peri/premenopausal women chemerin was inversely associated with BUA
      levels; after multivariable adjustment, a 10% increase in the chemerin
      concentration was significantly associated with 0.83 dB/MHz lower BUA levels (P =
      0.0006). In postmenopausal women chemerin was not related to BUA levels (P =
      0.8). CONCLUSION: The present study provides evidence for an inverse association
      between chemerin and BUA in peri/premenopausal women. Therefore, the study
      suggests that high chemerin concentrations may minimize peak bone mass and
      thereby may promote age-related bone loss. Further studies are needed to
      investigate the role of chemerin in bone homeostasis in peri/premenopausal and
      postmenopausal women.

PMID- 29206772
TI  - Letter to the Editor.

PMID- 29206771
TI  - Vasomotor symptom characteristics: are they risk factors for incident diabetes?
AB  - OBJECTIVE: Vasomotor symptoms (VMS), encompassing hot flashes and night sweats,
      may be associated with diabetes, but evidence is limited. We sought to estimate
      these associations. METHODS: Among 150,007 postmenopausal Women's Health
      Initiative participants from 1993 to 2014, we prospectively examined associations
      of incident diabetes with VMS characteristics at enrollment: any VMS, severity
      (mild/ moderate/severe), type (hot flashes/night sweats), timing (early
      [premenopausal or perimenopausal]/late [postmenopausal]), and duration. Cox
      proportional-hazards models estimated hazard ratios (HRs) and 95% confidence
      intervals (CIs). RESULTS: Mean duration of follow-up was 13.1 years. VMS
      prevalence was 33%. Reporting any VMS was associated with 18% increased diabetes
      risk (95% CI 1.14, 1.22), which increased with severity (mild: HR 1.13, 95% CI
      1.08, 1.17; moderate: HR 1.29, 95% CI 1.22, 1.36; severe: HR 1.48, 95% CI 1.34,
      1.62) and duration (4% per 5 years, 95% CI 1.03, 1.05), independent of obesity.
      Diabetes risk was more pronounced for women reporting any night sweats (night
      sweats only: HR 1.20, 95% CI 1.13, 1.26; night sweats and hot flashes: HR 1.22,
      95% CI 1.17, 1.27) than only hot flashes (HR 1.08, 95% CI 1.02, 1.15) and was
      restricted to late VMS (late: HR 1.12, 95% CI 1.07, 1.18; early and late: HR
      1.16, 95% CI 1.11, 1.22; early: HR 0.99, 95% CI 0.95, 1.04). CONCLUSIONS: VMS are
      associated with elevated diabetes risk, particularly for women reporting night
      sweats and postmenopausal symptoms. The menopause transition may be an optimal
      window for clinicians to discuss long-term cardiovascular/metabolic risk with
      patients and leverage the bother of existing symptoms for behavior change to
      improve VMS and reduce diabetes risk.

PMID- 29206773
TI  - Trauma exposure and endothelial function among midlife women.
AB  - OBJECTIVE: Trauma is a potent exposure that can have implications for health.
      However, little research has considered whether trauma exposure is related to
      endothelial function, a key process in the pathophysiology of cardiovascular
      disease (CVD). We tested whether exposure to traumatic experiences was related to
      poorer endothelial function among midlife women, independent of CVD risk factors,
      demographic factors, psychosocial factors, or a history of childhood abuse.
      METHODS: In all, 272 nonsmoking perimenopausal and postmenopausal women aged 40
      to 60 years without clinical CVD completed the Brief Trauma Questionnaire, the
      Child Trauma Questionnaire, physical measures, a blood draw, and a brachial
      ultrasound for assessment of brachial artery flow-mediated dilation (FMD).
      Relations between trauma and FMD were tested in linear regression models
      controlling for baseline vessel diameter, demographics, depression/anxiety, CVD
      risk factors, health behaviors, and, additionally, a history of childhood abuse.
      RESULTS: Over 60% of the sample had at least one traumatic exposure, and 18% had
      three or more exposures. A greater number of traumatic exposures was associated
      with lower FMD, indicating poorer endothelial function in multivariable models
      (beta, beta [standard error, SE] -1.05 [0.40], P = 0.01). Relations between
      trauma exposure and FMD were particularly pronounced for three or more trauma
      exposures (b [SE] -1.90 [0.71], P = 0.008, relative to no exposures,
      multivariable). CONCLUSIONS: A greater number of traumatic exposures were
      associated with poorer endothelial function. Relations were not explained by
      demographics, CVD risk factors, mood/anxiety, or a by history of childhood abuse.
      Women with greater exposure to trauma over life maybe at elevated CVD risk.

PMID- 29206775
TI  - Menopause improves the predictive value of common cardiovascular risk scores in
      women with premature coronary artery disease.
AB  - OBJECTIVE: Menopause, particularly its early stage (<=3 years from onset), may be
      an important risk factor for premature coronary artery disease. The objective of
      the study was to assess whether the addition of the presence of menopause in
      women with premature coronary artery disease could improve the predictive value
      of the Atherosclerotic Cardiovascular Disease risk estimator and the Systematic
      COronary Risk Evaluation model. METHODS: The case-control study included 307
      women with coronary artery disease aged 55 or less, and 347 age-matched controls
      without coronary artery disease. Diagnostic accuracy parameters were evaluated
      for traditional risk models versus those enriched with menopausal status. Early
      and late postmenopausal periods were defined as <=3 and >3 years from the onset
      of menopause, respectively. RESULTS: Only the addition of the presence of the
      early postmenopausal stage to the 10-year Atherosclerotic Cardiovascular Disease
      risk classes resulted in significantly increased c-statistics from 0.66 (95%
      confidence interval [CI] 0.62-0.7) to 0.705 (95%CI 0.66-0.75) (P = 0.0003) and an
      increase of accuracy from 61.3% to 63.8% (P = 0.0025).Adding the presence of
      early postmenopause to the Systematic COronary Risk Evaluation risk classes also
      resulted in significantly increased c-statistics from 0.59 (95% CI 0.55-0.63) to
      0.641 (95%CI 0.6-0.68) (P = 0.0024) and an increase of accuracy from 64.1% versus
      57.5% (P = 0.001). CONCLUSION: Adding the early menopausal period may
      significantly improve the predictive value of the 10-year Atherosclerotic
      Cardiovascular Disease risk score and the Systematic COronary Risk Evaluation
      model in women with premature coronary artery disease.

PMID- 29206776
TI  - In Reply.

PMID- 29206774
TI  - Associations between improvement in genitourinary symptoms of menopause and
      changes in the vaginal ecosystem.
AB  - OBJECTIVE: The aim of the study was to identify associations between improvement
      in genitourinary symptoms of menopause (GSM) and vaginal microbiota, vaginal
      glycogen, and serum estrogen. METHODS: Thirty postmenopausal women enrolled in a
      hot flash treatment trial (oral estradiol vs venlafaxine vs placebo) who reported
      GSM and provided vaginal swabs at 0, 4, and 8 weeks were studied. Bacterial
      communities were characterized using deep sequencing targeting the 16S rRNA gene
      V3-V4 region. Participants selected a most bothersome genitourinary symptom
      (dryness, discharge, pain, itch/burn, or inability to have sex) and rated
      severity on a 10-point scale at baseline and 8 weeks. Vaginal glycogen and serum
      estradiol and estrone were measured at enrollment and 8 weeks. Comparisons
      according to improvement in most bothersome symptom (MBS) were made using chi,
      Wilcoxon signed-rank test, or Hotelling's t test. RESULTS: Of 30 participants, 21
      (70%) had improvement in MBS over the 8-week study and 9 (30%) had no improvement
      or worsening of MBS. A higher proportion of women receiving estradiol or
      venlafaxine reported improvement in MBS (88%, 78%) compared with placebo (54%; P
      = 0.28). MBS improvement was associated with Lactobacillus-dominant vaginal
      microbiota at enrollment (57% vs 22%, P = 0.08). Vaginal glycogen, serum
      estradiol, and estrone significantly increased in women whose MBS improved.
      CONCLUSIONS: A larger proportion of women whose MBS improved had a Lactobacillus
      dominant microbiota at enrollment than those who had no improvement during the
      trial, though this difference was not statistically significant. Larger trials
      are needed to determine whether vaginal microbiota modify or mediate treatment
      responses in women with GSM.

PMID- 29206777
TI  - To the Editor.

PMID- 29206778
TI  - Urinary incontinence: finding a voice to talk about "it".

PMID- 29206779
TI  - Concentration range of serum sex steroids in normal postmenopausal women and
      those with diagnosis of vulvovaginal atrophy.
AB  - OBJECTIVE: The aim of the study was to determine the range of serum sex-related
      steroids in normal postmenopausal women and in women of the same age with a
      diagnosis of vulvovaginal atrophy (VVA). METHODS: Validated mass spectrometry
      based assays coupled to gas or liquid chromatography were used over a 10-year
      period for steroid measurements. Serum samples were obtained in up to 1,512 women
      aged 55 to 65 years. RESULTS: Serum estrone sulfate (E1S) and androsterone
      glucuronide (ADT-G), the main metabolites of estrogens and androgens,
      respectively, were 16.9% (P = 0.005) and 16.1% (P = 0.001) higher in women not
      diagnosed with moderate/severe VVA than those diagnosed with VVA. Serum estrone
      (E1) was 14.5% (P < 0.0001) higher in women with no diagnosis of VVA, whereas the
      other steroids did not show meaningful differences. The limited biological
      significance of serum estradiol (E2) and testosterone is supported by the lack of
      statistical significance in the serum concentrations of these two steroids
      between the two groups. Most importantly, for the women without a diagnosis of
      VVA, the normal upper limit (95 centile) of serum E2 was 9.15 pg/mL (n = 364) and
      10.7 pg/mL (n = 67) for a weighted average of 9.99 pg E2/mL. A limit of 10 pg
      E2/mL has recently been found by two other laboratories. When comparing 50- to 59
      year-old and 70- to 79-year-old women, serum E2, E1S, ADT-G, and DHEA were,
      respectively, 24.4%, 22.6%, 27.0%, and 85.9% higher in the younger group.
      CONCLUSIONS: Somewhat higher values, namely, 16.9% and 16.1%, are observed in the
      serum concentrations of the estrogen (E1S) and androgen (ADT-G) metabolites in
      normal compared with women with a diagnosis of VVA. Such data indicating a lower
      estrogenic and androgenic global exposure in women diagnosed with VVA offers an
      opportunity for the local intravaginal administration of DHEA to replace the
      deficiency in endogenous DHEA.

PMID- 29206780
TI  - Neoadjuvant strategies for advanced pancreatic neuroendocrine tumors: should
      combined chemotherapy and peptide receptor radionuclide therapy be the preferred
      regimen for maximizing outcome?

PMID- 29206781
TI  - Perceptual Responses to High- and Moderate-Intensity Interval Exercise in
      Adolescents.
AB  - PURPOSE: Continuous high-intensity exercise is proposed to evoke unpleasant
      sensations as predicted by the dual-mode theory and may negatively impact on
      future exercise adherence. Previous studies support unpleasant sensations in
      affective responses during continuous high-intensity exercise, but the affect
      experience during high-intensity interval exercise (HIIE) involving brief bursts
      of high-intensity exercise separated by low-intensity activity is poorly
      understood in adolescents. We examined the acute affective, enjoyment, and
      perceived exertion responses to HIIE compared with moderate-intensity interval
      exercise (MIIE) in adolescents. METHODS: Thirteen adolescent boys (mean +/- SD:
      age, 14.0 +/- 0.5 yr) performed two counterbalanced exercise conditions: 1) HIIE:
      8 * 1-min work intervals at 90% maximal aerobic speed; and 2) MIIE: between 9 and
      12 * 1-min work intervals at 90% ventilatory threshold where the number of
      intervals performed were distance-matched to HIIE. HIIE and MIIE work intervals
      were interspersed with 75 s active recovery at 4 km.h. Affect, enjoyment, and RPE
      were recorded before, during, and after exercise. RESULTS: Affect responses
      declined in both conditions but the fall was greater in HIIE than MIIE (P <
      0.025, effect size [ES], 0.64 to 0.81). Affect remained positive at the end-work
      interval for both conditions (MIIE, 2.62 +/- 1.50; HIIE, 1.15 +/- 2.08 on feeling
      scale). No enjoyment differences were evident during HIIE and MIIE (P = 0.32),
      but HIIE elicited greater postexercise enjoyment compared with MIIE (P = 0.01, ES
      = 0.47). RPE was significantly higher during HIIE than MIIE across all work
      intervals (all P < 0.03, ES > 0.64). CONCLUSIONS: Despite elevated RPE, HIIE did
      not elicit prominent unpleasant feelings as predicted by the dual-mode theory and
      was associated with greater postexercise enjoyment responses than MIIE. This
      study demonstrates the feasibility of the application of HIIE as an alternative
      form of physical activity in adolescents.

PMID- 29206782
TI  - Muscle Fiber and Performance Changes after Fast Eccentric Complex Training.
AB  - INTRODUCTION: The purpose of this study was to examine the effects of a short
      term fast eccentric and ballistic complex training program on muscle power, rate
      of force development (RFD), muscle fiber composition, and cross-sectional area
      (CSA). METHODS: Sixteen male physical education students were randomly assigned
      to either a training group (TG, n = 8) or a control group (n = 8). The TG
      followed a 6-wk low volume training program, including fast eccentric squat
      training with an individually optimized load of 74% +/- 7% of maximal half-squat
      strength (1RM) twice per week and a ballistic training session with loaded (30%
      1RM) and unloaded jump squats, once per week, all combined with unloaded
      plyometric jumps. RESULTS: Half squat 1RM was increased in the TG from 1.87 +/-
      0.28 to 2.14 +/- 0.31 kg per kilogram body mass (14.4% +/- 9.3%, P = 0.01). The
      percentage of types I, IIA, and IIX fibers were similar in the two groups at
      pretesting and did not change after the intervention period (P = 0.53-0.89).
      Muscle fiber CSA increased in all fiber types by 8.3% to 11.6% (P = 0.02 to
      0.001) in TG only. Countermovement jump height and peak power measured at five
      different external loads (0%-65% of 1RM) only increased in the TG by
      approximately 20% to 36% (P < 0.01) and approximately 16% to 22% (P < 0.01),
      respectively. Peak ground reaction force during jump squats remained unchanged in
      both groups, whereas RFD increased in the TG only (40%-107%, P = 0.001).
      CONCLUSIONS: A combination of low-volume fast eccentric and ballistic jump squat
      training with plyometric jumps in a strength-power potentiation complex format,
      induced substantial increases in peak leg muscle power, RFD, and maximal
      strength, accompanied by gains in CSA of all muscle fiber types, without a
      reduction in fast twitch fiber composition.

PMID- 29206783
TI  - Protocol for Objective Measurement of Infants' Physical Activity using
      Accelerometry.
AB  - PURPOSE: This study aimed to evaluate methods for infants' physical activity
      measurement based on accelerometry, including the minimum number of measurement
      days and placement of a wrist or ankle device. We also evaluated the
      acceptability of the device among infants and mothers. METHODS: A cross-sectional
      mixed-methods study was conducted on a convenience sample of 90 infants. Physical
      activity was measured using the Actigraph GT3X+ accelerometer placed on the wrist
      and/or ankle for 7 consecutive days (worn for 24 h), and a qualitative interview
      was performed to verify acceptability. The intraclass correlation coefficient
      (ICC) method and the Bland and Altman's dispersion diagram were used to verify
      the minimum number of measurement days. All analyses were stratified by walking
      status. RESULTS: The mean (SD) age was 12.9 (1.70) months; the mean acceleration
      varied between 25.8 mg (95% confidence interval (CI), 14.3-52.7) and 27.3 mg (95%
      CI, 17.9-44.5) using the wrist placement, and between 24.9 mg (95% CI, 10.6-48.4)
      and 26.2 mg (95% CI, 11.7-65.6) using the ankle placement. The ICC results showed
      a lower acceleration variability between days among infants incapable of walking;
      they achieved an ICC of 0.80 with 1 d of measurement in both placements. Among
      those capable of walking, the minimum number of days to achieve an ICC of 0.80
      was 2 d measured at the wrist (0.85; 95% CI, 0.71-0.93) and 3 d measured at the
      ankle (0.92; 95% CI, 0.84-0.96). The qualitative results pointed to the wrist
      placement as the preferred placement among the overall sample. CONCLUSIONS: Two
      and three measurement days with the accelerometer placed on the wrist and ankle,
      respectively, seemed to adequately represent a week of measurement. The
      accelerometer placed on the wrist had better acceptance by the infants and
      mothers.

PMID- 29206784
TI  - Effect of Beta-blocker Treatment on VO2peak in Patients with Heart Failure.
AB  - PURPOSE: In addition to prolonged life and reduced hospitalization rates, it is
      currently unclear whether beta-blocker (BB) treatment modulates peak oxygen
      consumption (VO2peak), a hallmark of exercise capacity, in patients with heart
      failure (HF). The main aim of this study is to determine the effect of BB
      treatment on VO2peak in HF patients. METHODS: We conducted a systematic search of
      MEDLINE, Scopus, and Web of Science since their inceptions until March 2017 for
      randomized controlled trials (RCT) assessing the effect of BB treatment on
      VO2peak in chronic HF patients. A meta-analysis was performed to ascertain the
      standardized mean difference (SMD) between the effects of BB and placebo
      treatment on VO2peak. Secondary outcomes included peak exercise performance and
      New York Health Association functional class. Subgroup and meta-regression
      analyses assessed potential moderating factors. RESULTS: Fourteen RCT met the
      inclusion criteria (overall n = 616). Interventions comprised BB (n = 324) or
      placebo (n = 292) administration lasting 3 to 24 months. Concomitant reported
      medication did not differ between HF patients assigned to BB and placebo groups.
      After data pooling, VO2peak was preserved with BB compared with placebo treatment
      (SMD, -0.04; 95% confidence interval (CI), -0.20 to 0.12; P = 0.61);
      heterogeneity among studies was not detected (I = 0%, P = 0.88). Peak exercise
      performance was not altered (SMD, 0.02; 95% CI, -0.16 to 0.20; P = 0.85), whereas
      New York Health Association functional class was reduced with BB compared with
      placebo (SMD, -0.54; 95% CI, -0.90 to -0.18; P = 0.003). CONCLUSIONS: According
      to evidence from RCT, prolonged BB (B1-selective or nonselective) treatment does
      not affect VO2peak but improves functional status in HF patients.

PMID- 29206785
TI  - Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.
AB  - PURPOSE: Overload training is hypothesized to alter autonomic regulation,
      although interpretations using indirect measures of heart rate variability are
      conflicting. The aim of the present study was to examine the effects of overload
      training on muscle sympathetic nerve activity (MSNA), a direct measure of central
      sympathetic outflow, in recreational endurance athletes. METHODS: Measurements of
      heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA
      (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes
      and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of
      either regular (n = 7) or overload (n = 10) training. RESULTS: After training,
      the changes (Delta) in peak power output (10 +/- 10 vs -12 +/- 9 W, P < 0.001),
      maximal heart rate (-2 +/- 4 vs -8 +/- 3 bpm, P = 0.006), heart rate variability
      (SD of normal-to-normal intervals, 27 +/- 31 vs -3 +/- 25 ms; P = 0.04), and
      cardiac BRS (7 +/- 6 vs -2 +/- 8 ms.mm Hg, P = 0.02) differed between the control
      and overload groups. The change in MSNA burst frequency (-2 +/- 2 vs 4 +/- 5
      bursts per minute, P = 0.02) differed between groups. Across all participants,
      the changes in resting MSNA and peak power output were correlated negatively (r =
      -0.51, P = 0.04). No between-group differences in resting heart rate or blood
      pressure were observed (all P > 0.05). CONCLUSIONS: Overload training increased
      MSNA and attenuated increases in cardiac BRS and heart rate variability observed
      with regular training. These results support neural adaptations after overload
      training and suggest that increased central sympathetic outflow may be linked
      with decreased exercise performance.

PMID- 29206786
TI  - Same-Day Discharge Compared with Inpatient Hospitalization Following Hip and Knee
      Arthroplasty.
AB  - BACKGROUND: Discharge from the hospital on the day of (same-day) hip and knee
      arthroplasties has become more common; however, to our knowledge, few studies
      have compared morbidity between same-day and inpatient surgical procedures. The
      aims of this study were to compare matched cohorts of patients who underwent same
      day and inpatient hip or knee arthroplasty in terms of postoperative
      complications and 30-day readmission rates. METHODS: Patients who underwent
      primary elective total hip arthroplasty, total knee arthroplasty, or
      unicompartmental knee arthroplasty from 2005 to 2014 were identified from the
      National Surgical Quality Improvement Program registry. Patients discharged the
      day of the surgical procedure were matched 1:1 with patients who had an inpatient
      stay using propensity scores. The rates of 30-day adverse events and readmission
      were compared between matched cohorts using the McNemar test. Risk factors for 30
      day readmission following same-day procedures were identified using multivariate
      regression. RESULTS: Of 177,818 patients identified, 1,236 (0.70%) underwent a
      same-day surgical procedure. After matching, there were no differences in overall
      adverse events or readmission between same-day and inpatient groups, although
      inpatients had increased thromboembolic events (p = 0.048) and same-day patients
      had an increased rate of return to the operating room (p = 0.016). When
      procedures were assessed individually, the only difference identified was that
      the same-day total knee arthroplasty cohort had an increased return to the
      operating room compared with the inpatient total knee arthroplasty cohort (p =
      0.046). Body mass index of >=35 kg/m (p = 0.035), insulin-dependent diabetes (p =
      0.041), non-insulin-dependent diabetes (p = 0.013), and age of >=85 years (p =
      0.039) were associated with 30-day readmission following same-day surgical
      procedures. Infection was the most common reason for reoperation and readmission
      following same-day procedures. CONCLUSIONS: No significant differences in overall
      postoperative complications or readmission were found between matched cohorts of
      patients who underwent same-day and inpatient hip and knee arthroplasties,
      although inpatients had a higher rate of thromboembolic events and same-day
      patients had a higher rate of reoperation. Patients with a body mass index of
      >=35 kg/m, diabetes, and an age of >=85 years had an increased risk of 30-day
      readmission following same-day procedures, which was most commonly due to
      infection. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29206787
TI  - Outpatient Total Knee Arthroplasty Is Associated with Higher Risk of
      Perioperative Complications.
AB  - BACKGROUND: As concerns regarding health-care expenditure in the U.S. remain at
      the national forefront, outpatient arthroplasty is an appealing option for
      carefully selected patient populations. The purpose of this study was to
      determine the nationwide trends and complication rates associated with outpatient
      total knee arthroplasty (TKA) in comparison with standard inpatient TKA. METHODS:
      We performed a retrospective review of the Humana subset of the PearlDiver
      Patient Record Database to identify patients who had undergone TKA (Current
      Procedural Terminology [CPT] code 27447) as either outpatients or inpatients from
      2007 to 2015. The incidence of perioperative medical and surgical complications
      was determined by querying for relevant International Classification of Diseases,
      Ninth Revision (ICD-9) and CPT codes. Multivariate logistic regression analysis
      adjusted for age, sex, and Charlson Comorbidity Index (CCI) was used to calculate
      odds ratios (ORs) of complications among outpatients relative to inpatients
      treated with TKA. RESULTS: Cohorts of 4,391 patients who underwent outpatient TKA
      and 128,951 patients who underwent inpatient TKA were identified. The median age
      was in the 70 to 74-year age group in both cohorts. The incidence of outpatient
      TKA increased across the study period (R = 0.60, p = 0.015). After adjustment for
      age, sex, and CCI, outpatient TKAs were found to more likely be followed by
      tibial and/or femoral component revision due to a noninfectious cause (OR = 1.22,
      95% confidence interval [CI] = 1.01 to 1.47; p = 0.039), explantation of the
      prosthesis (OR = 1.35, CI = 1.07 to 1.72; p = 0.013), irrigation and debridement
      (OR = 1.50, CI = 1.28 to 1.77; p < 0.001), and stiffness requiring manipulation
      under anesthesia (OR = 1.28, CI = 1.17 to 1.40; p < 0.001) within 1 year.
      Outpatient TKA was also more frequently associated with postoperative deep vein
      thrombosis (OR = 1.42, CI = 1.25 to 1.63; p < 0.001) and acute renal failure (OR
      = 1.13, CI = 1.01 to 1.25; p = 0.026). CONCLUSIONS: With the potential to
      minimize arthroplasty costs among healthy patients, outpatient TKA is an
      increasingly popular option. Nationwide data from a private insurance database
      demonstrated a higher risk of perioperative surgical and medical complications
      including component failure, surgical site infection, knee stiffness, and deep
      vein thrombosis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29206788
TI  - Matrix-Induced Autologous Chondrocyte Implantation (MACI) Using a Cell-Seeded
      Collagen Membrane Improves Cartilage Healing in the Equine Model.
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) using a collagen scaffold
      (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that
      provides the benefit of autologous cells and guided tissue regeneration using a
      biocompatible collagen scaffold. The MACI implant also has inherent advantages
      including surgical implantation via arthroscopy or miniarthrotomy, the
      elimination of periosteal harvest, and the use of tissue adhesive in lieu of
      sutures. This study evaluated the efficacy of the MACI implant in an equine full
      thickness cartilage defect model at 1 year. METHODS: Autologous chondrocytes were
      seeded onto a collagen type-I/III membrane and implanted into one of two 15-mm
      defects in the femoral trochlear ridge of 24 horses. Control defects either were
      implanted with cell-free collagen type-I/III membrane (12 horses) or were left
      ungrafted as empty defects (12 horses). An additional 3 horses had both 15-mm
      defects remain empty as nonimplanted joints. The repair was scored by second-look
      arthroscopy (12 weeks), and necropsy examination (53 weeks). Healing was assessed
      by arthroscopic scoring, gross assessment, histology and immunohistology,
      cartilage matrix component assay, and gene expression determination. Toxicity was
      examined by prostaglandin E2 formation in joint fluid, and lymph node morphology
      combined with histologic screening of organs. RESULTS: MACI-implanted defects had
      improved gross healing and composite histologic scores, as well as increases in
      chondrocyte predominance, toluidine blue-stained matrix, and collagen type-II
      content compared with scaffold-only implanted or empty defects. There was minimal
      evidence of reaction to the implant in the synovial membrane (minor perivascular
      cuffing), subchondral bone, or cartilage. There were no adverse clinical effects,
      signs of organ toxicity, or evidence of chondrocytes or collagen type-I/III
      membrane in draining lymph nodes. CONCLUSIONS: The MACI implant appeared to
      improve cartilage healing in a critical-sized defect in the equine model compared
      with collagen matrix alone. CLINICAL RELEVANCE: These results indicate that the
      MACI implant is quick to insert, provides chondrocyte security in the defect, and
      improves cartilage healing compared with ACI.

PMID- 29206789
TI  - Functional Outcomes of the Ream-and-Run Shoulder Arthroplasty: A Concise Follow
      up of a Previous Report.
AB  - : We previously reported the results at an average of 4.5 years after treatment
      of 176 patients with the ream-and-run arthroplasty. In the present study, we
      present the patient self-reported functional outcomes and clinical implant
      survival of the original cohort at a mean of 10 years (range, 5 to 16 years).
      Twenty-eight (16%) of the 176 patients had a subsequent procedure, 11 (6%) died,
      and 30 (17%) had <5 years of follow-up. The Simple Shoulder Test (SST) score at
      the time of the latest follow-up was a median of 11 points (interquartile range,
      9 to 12 points) and a mean (and standard deviation) of 10 +/- 2.6 points, out of
      a possible 12 points. The present study demonstrates that the improvement in
      function and comfort derived from the ream-and-run procedure can be sustained at
      the time of mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29206790
TI  - Aspirin for Prophylaxis Against Venous Thromboembolism After Orthopaedic
      Oncologic Surgery.
AB  - BACKGROUND: Patients who undergo orthopaedic oncologic surgical procedures are at
      increased risk of developing a venous thromboembolism (VTE). Guidelines from
      surgical societies are shifting to include aspirin as a postoperative VTE
      prophylactic agent. The purpose of this study was to review our experience using
      aspirin as postoperative VTE prophylaxis for orthopaedic oncologic surgical
      procedures. METHODS: This study was a retrospective review of patients diagnosed
      with a primary malignant soft-tissue or bone tumor or metastatic carcinoma.
      Demographic information, histopathologic diagnosis, VTE history, surgical
      procedure, and VTE prophylaxis were analyzed. VTE rates in the overall and
      prophylactic-specific cohorts were recorded and compared. RESULTS: A total of 142
      distinct surgical procedures in 130 patients were included. VTE prophylaxis with
      aspirin was used after 103 procedures, and non-aspirin prophylaxis was used after
      39. In 33 cases, imaging was used to investigate for VTE because of clinical
      signs and symptoms. VTE developed after 7 (4.9%) of the 142 procedures. There
      were 6 deep venous thromboses (DVTs) and 1 pulmonary embolism, and 2 of the VTEs
      presented in patients with a VTE history. VTE developed in 2.9% (3) of the 103
      aspirin cases and 10.3% (4) of the 39 non-aspirin cases. No patient in the
      aspirin group who had been diagnosed with metastatic carcinoma, malignant soft
      tissue sarcoma, lymphoma, or multiple myeloma developed a VTE. Risk factors for
      VTE development included diabetes mellitus (odds ratio [OR] = 10.40, 95%
      confidence interval [CI] = 1.61 to 67.30), a history of VTE (OR = 7.26, 95% CI =
      1.19 to 44.25), postoperative transfusion (OR = 34.50, 95% CI = 3.94 to 302.01),
      and estimated blood losses of 250 mL (OR = 1.50, 95% CI = 1.11 to 2.03), 500 mL
      (OR = 2.26, 95% CI = 1.23 to 4.13), and 1,000 mL (OR = 5.10, 95% CI = 1.52 to
      17.04). CONCLUSIONS: Aspirin may be a suitable and effective option for VTE
      chemoprophylaxis in patients treated with orthopaedic oncologic surgery,
      especially those diagnosed with a soft-tissue sarcoma. Research with a more
      advanced study design is required. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29206791
TI  - Irrigation and Debridement with Component Retention for Acute Infection After Hip
      Arthroplasty: Improved Results with Contemporary Management.
AB  - BACKGROUND: There are conflicting data on the results of irrigation and
      debridement with component retention in patients with acute periprosthetic hip
      infections. The goals of this study were to examine contemporary results of
      irrigation and debridement with component retention for acute infection after
      primary hip arthroplasty and to identify host, organism, antibiotic, or implant
      factors that predict success or failure. METHODS: Ninety hips (57 total hip
      arthroplasties and 33 hemiarthroplasties) were diagnosed with acute
      periprosthetic hip infection (using strict criteria) and were treated with
      irrigation and debridement and component retention between 2000 and 2012. The
      mean follow-up was 6 years. Patients were stratified on the basis of McPherson
      criteria. Hips were managed with irrigation and debridement and retention of well
      fixed implants with modular head and liner exchange (70%) or irrigation and
      debridement alone (30%). Seventy-seven percent of patients were treated with
      chronic antibiotic suppression. Failure was defined as failure to eradicate
      infection, characterized by a wound fistula, drainage, intolerable pain, or
      infection recurrence caused by the same organism strain; subsequent removal of
      any component for infection; unplanned second wound debridement for ongoing deep
      infection; and/or occurrence of periprosthetic joint infection-related mortality.
      RESULTS: Treatment failure occurred in 17% (15 of 90 hips), with component
      removal secondary to recurrent infection in 10% (9 of 90 hips). Treatment failure
      occurred in 15% (10 of 66 hips) after early postoperative infection and 21% (5 of
      24 hips) after acute hematogenous infection (p = 0.7). Patients with McPherson
      host grade A had a treatment failure rate of 8%, compared with 16% (p = 0.04) in
      host grade B and 44% in host grade C (p = 0.006). Most treatment failures (12 of
      15 failures) occurred within the initial 6 weeks of treatment; failures
      subsequent to 6 weeks occurred in 3% of those treated with chronic antibiotic
      suppression compared with 11% of those who were not treated with suppression
      (hazard ratio, 4.0; p = 0.3). CONCLUSIONS: The success rate was higher in this
      contemporary series than in many previous series. Systemic host grade A was
      predictive of treatment success. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29206792
TI  - Direct Anterior Hip Replacement Does Not Pose Undue Radiation Exposure Risk to
      the Patient or Surgeon.
AB  - BACKGROUND: The fluoroscopically assisted direct anterior approach for total hip
      arthroplasty has gained interest in recent years. One of the perceived advantages
      is the use of fluoroscopy to aid in the positioning of implants. The purpose of
      this study was to measure the radiation entrance surface dose to anatomically
      important areas of both patients and surgeons during direct anterior approach
      total hip arthroplasty. METHODS: Radiation dosimetry badges were placed at the
      sternal notch and pubic symphysis of 50 patients undergoing direct anterior
      approach total hip arthroplasty. Badges were also placed on the surgeons outside
      of their lead aprons at the level of the thyroid. Three fellowship-trained
      arthroplasty surgeons were involved in the study. Radiation exposure of each
      badge was measured after each case (surgeon and patient). The cumulative dose was
      also calculated for the surgeons. To limit surgeon bias during the study, 50
      consecutive direct anterior approach total hip arthroplasties that occurred prior
      to this study were analyzed for total fluoroscopic dose and time and served as a
      control group. RESULTS: Forty-five subjects met study criteria. In the study
      group, 1 patient had a detectable thyroid exposure equal to 1 mrem. Seven
      patients had a detectable radiation entrance surface dose at the pubic symphysis
      (range, 1 to 7 mrem). No radiation entrance surface dose was detectable in the
      remaining 44 patients at the sternal notch and 38 patients at the pubic
      symphysis. Surgeons in the study did not experience a detectable radiation
      entrance surface dose. The mean fluoroscopic time was 13.72 seconds (range, 6.7
      to 28.7 seconds). The mean patient radiation exposure was 178 mrem (range, 54 to
      526 mrem). CONCLUSIONS: This study demonstrates that during direct anterior
      approach total hip arthroplasty, the mean patient entrance surface dose at the
      pubic symphysis and the sternal notch is not detectable in most patients. The
      mean patient exposure in this study during direct anterior approach total hip
      arthroplasty was 178 mrem, which is less than a single pelvic radiograph (600
      mrem). No surgeon in our study demonstrated a detectable radiation entrance
      surface dose. Our data suggest that direct anterior approach total hip
      arthroplasty typically results in a negligible or very low dose of absorbed
      radiation exposure to the patient and the surgeon. CLINICAL RELEVANCE: We believe
      this study to have clinical relevance because both patients and surgeons have
      evidence that utilization of fluoroscopy during direct anterior total hip
      replacement places both parties at a relatively low radiation exposure risk.

PMID- 29206793
TI  - Diagnosis and Management of Sacroiliac Joint Dysfunction.

PMID- 29206794
TI  - What's New in Musculoskeletal Basic Science.

PMID- 29206795
TI  - What's Important: What Constitutes Success in an Orthopaedic Career?: Defining
      Success Your Way.

PMID- 29206796
TI  - Overlapping and Concurrent Surgery: A Professional and Ethical Analysis.
AB  - Overlapping and concurrent surgeries form a continuum of simultaneous surgical
      practice in which a single surgeon has 2 or more patients in operating rooms at
      the same time. Undeniably, in an acute life-or-limb-threatening presentation, it
      may be essential for a surgeon to care for 2 individual patients simultaneously.
      These situations are different from scheduled elective surgery. Concurrent
      surgery is defined as the attending surgeon not being present for "critical and
      key" portions of a procedure. Billing for concurrent surgical procedures is a
      violation of the U.S. Centers for Medicare & Medicaid Services guidelines. The
      American College of Surgeons Statement of Principles (April 2016), adopted by the
      American Academy of Orthopaedic Surgeons, judges the practice of concurrent
      surgery to be "inappropriate." Overlapping surgery, although permissible under
      regulatory guidelines in the United States, presents substantial professional,
      bioethical, and legal concerns, and threatens our obligation as orthopaedic
      surgeons to respect the primacy of patient welfare and an individual's autonomy.

PMID- 29206797
TI  - Instability of the Hip Joint After Posterior Acetabular Wall Fracture:
      Independent Risk Factors Remain Elusive.
AB  - BACKGROUND: Exact determinants of hip instability have not been established for
      fractures of the posterior wall of the acetabulum involving <=50% of the wall.
      Therefore, examination of the hip under anesthesia (EUA) is routinely performed.
      Recently, the superior exit point of the fracture has been reported to be an
      important identifiable risk factor. Pre-existing adult hip dysplasia
      (developmental dysplasia of the hip [DDH]) is thought to have a similar role. The
      purpose of this study was to determine if any known radiographic measurements and
      signs associated with DDH, or any fracture characteristics, are independent risk
      factors for hip instability after fracture of the posterior wall of the
      acetabulum. METHODS: All patients with a posterior acetabular wall fracture (OTA
      62.A1) treated at our institution between 2004 and 2015 were considered for the
      study. Inclusion criteria were an age of >=18 years, an isolated posterior
      acetabular wall fracture involving <=50% of the acetabular wall, adequate
      imaging, and documented EUA results. Evaluated variables included fracture
      fragment size, superior exit point of the fracture, center-edge angle, acetabular
      index, Tonnis angle, lateralized head sign, crossover sign, posterior wall sign,
      ischial spine sign, and hip version. Data were examined using univariate testing,
      followed by a multivariate logistic regression analysis. RESULTS: Sixty-eight
      patients met all of the inclusion criteria. Univariate analyses identified the
      posterior wall sign (p = 0.033), ischial spine sign (p = 0.030), and proximity of
      the superior exit point of the fracture to the acetabular dome (p = 0.044) as
      having a significant association with hip instability. However, multivariate
      logistic regression modeling revealed that none of these factors were significant
      independent risk factors. CONCLUSIONS: Consistent with previous studies,
      univariate analyses identified certain radiographic findings as significant risk
      factors for hip instability in the setting of a fracture of the posterior wall of
      the acetabulum. However, subsequent multivariate logistic regression modeling
      showed that no studied variable was an independent risk factor. Our results
      indicate that important factors leading to hip instability are yet to be
      identified or the contributions of the measured variables are relatively small.
      Therefore, EUA should remain the main clinical determinant of hip stability
      status. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 29206798
TI  - A Novel Registration-Based Approach for 3D Assessment of Posttraumatic Distal
      Humeral Deformities.
AB  - BACKGROUND: With current 3-dimensional (3D) computer-based methods for the
      assessment of deformities, a surface registration method is applied to
      superimpose a computer model of the pathological bone onto a mirrored computer
      model of the contralateral side. However, because of bilateral differences,
      especially in humeral torsion, such template-based approaches may introduce bias
      in the assessment of a distal humeral deformity. We hypothesized that a novel
      registration approach might prove superior to the current approach in reducing
      such bias, thus yielding improved accuracy of 3D assessment of distal humeral
      deformities. METHODS: Three-dimensional triangular surface models were generated
      from computed tomographic (CT) data of 100 paired humeri without a pathological
      condition. Humeral segments of varying, predetermined lengths, excluding the
      distal part of the humerus, were defined. A surface registration algorithm was
      applied to superimpose the humeral models of both sides based on each selected
      segment. Humeral contralateral registration (HCR) errors, defined as the residual
      differences in apparent 3D orientation between the distal parts, were evaluated.
      RESULTS: The mean HCR error (and standard deviation) using the distal-most
      humeral shaft segment to assess the angular orientation was 2.3 degrees  +/- 1.1
      (range, 0.5 degrees  to 5.8 degrees ). Including the humeral head in the surface
      registration algorithm, however, as is done currently, resulted in a higher HCR
      error (p < 0.001). The HCR error using the proximal-most segment was >10 degrees 
      in 20% of the cases and between 5 degrees  and 10 degrees  in an additional 50%
      of the cases. By comparison, using the proposed distal-most humeral shaft
      segment, the HCR error was between 5 degrees  and 10 degrees  in only 2% of
      cases, and was never >10 degrees . The proximal segments are nevertheless used in
      the proposed method for registering humeral length. CONCLUSIONS: The proposed new
      approach yields a deformity assessment that is less prone to bias arising from
      inherent bilateral differences and therefore is more accurate than current
      surface registration approaches. CLINICAL RELEVANCE: Accurate 3D assessment is of
      fundamental importance if computer-based methods are applied in the correction of
      posttraumatic deformities.

PMID- 29206799
TI  - Simulation-Based Educational Module Improves Intern and Medical Student
      Performance of Closed Reduction and Percutaneous Pinning of Pediatric
      Supracondylar Humeral Fractures.
AB  - BACKGROUND: Simulation-based education has been integrated into many orthopaedic
      residency programs to augment traditional teaching models. Here we describe the
      development and implementation of a combined didactic and simulation-based course
      for teaching medical students and interns how to properly perform a closed
      reduction and percutaneous pinning of a pediatric supracondylar humeral fracture.
      METHODS: Subjects included in the study were either orthopaedic surgery interns
      or subinterns at our institution. Subjects all completed a combined didactic and
      simulation-based course on pediatric supracondylar humeral fractures. The first
      part of this course was an electronic (e)-learning module that the subjects could
      complete at home in approximately 40 minutes. The second part of the course was a
      20-minute simulation-based skills learning session completed in the simulation
      center. Subject knowledge of closed reduction and percutaneous pinning of
      supracondylar humeral fractures was tested using a 30-question, multiple-choice,
      written test. Surgical skills were tested in the operating room or in a simulated
      operating room. Subject pre-intervention and post-intervention scores were
      compared to determine if and how much they had improved. RESULTS: A total of 21
      subjects were tested. These subjects significantly improved their scores on both
      the written, multiple-choice test and skills test after completing the combined
      didactic and simulation module. Prior to the module, intern and subintern
      multiple-choice test scores were significantly worse than postgraduate year (PGY)
      2 to PGY-5 resident scores (p < 0.01); after completion of the module, there was
      no significant difference in the multiple-choice test scores. After completing
      the module, there was no significant difference in skills test scores between
      interns and PGY-2 to PGY-5 residents. Both tests were validated using the scores
      obtained from PGY-2 to PGY-5 residents. CONCLUSIONS: Our combined didactic and
      simulation course significantly improved intern and subintern understanding of
      supracondylar humeral fractures and their ability to perform a closed reduction
      and percutaneous pinning of these fractures.

PMID- 29206801
TI  - Wishing It True Doesn't Make It So: Commentary on an article by Gregory M.
      Mendez, MD, et al.: "Aspirin for Prophylaxis Against Venous Thromboembolism After
      Orthopaedic Oncologic Surgery".

PMID- 29206800
TI  - Outpatient Total Joint Arthroplasty: An Evolving Concept: Commentary on an
      article by Armin Arshi, MD, et al.: "Outpatient Total Knee Arthroplasty Is
      Associated with Higher Risk of Perioperative Complications".

PMID- 29206802
TI  - Another Option in the Armamentarium: Understanding the Role of Irrigation and
      Debridement to Treat Hip Periprosthetic Joint Infection: Commentary on an article
      by Andrew J. Bryan, MD, et al.: "Irrigation and Debridement with Component
      Retention for Acute Infection After Hip Arthroplasty. Improved Results with
      Contemporary Management".

PMID- 29206803
TI  - Clinical Indicators of the Need for Telemetry Postoperative Monitoring in
      Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee
      Arthroplasty.
AB  - BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with increased
      complication rates postoperatively. Current literature does not provide adequate
      guidance on management of these patients. This study used the STOP-Bang
      questionnaire to diagnose patients with possible obstructive sleep apnea (score
      >=3). We hypothesized that a STOP-Bang score of 3 or greater would significantly
      correlate with the number of oxygen desaturation episodes during the first 48
      hours after total knee arthroscopy. METHODS: The STOP-Bang questionnaire was
      administered to 110 patients preoperatively. All patients underwent spinal
      epidural anesthesia with a saphenous nerve block and sedation and were connected
      to the Nellcor OxiMax N-600x pulse oximeter for 48 hours postoperatively.
      RESULTS: Final analysis included 98 patients. There was no significant difference
      in the total number of desaturation events between STOP-Bang groups (score <3 vs
      >=3 and score <5 vs >=5). The total number of desaturation events on
      postoperative day 1 was greater than that on day 0 (32.8 +/- 42.7 vs 4.1 +/-
      10.0, P < 0.0001). The total number of desaturation events correlated with length
      of hospital stay (r = 0.329, P = 0.0001). Patients with a preoperative serum CO2
      of 30 mmol/L or greater had significantly longer episodes of desaturation on
      postoperative day 0 compared with CO2 of less than 30 mmol/L (233.7 +/- 410.1 vs
      82.0 +/- 126.2 seconds, P = 0.044). CONCLUSIONS: A high preoperative value of CO2
      should be a warning for possible prolonged episodes of desaturation
      postoperatively. An attempt to limit postoperative desaturation events should be
      made to minimize length of stay.

PMID- 29206804
TI  - Comparison of Endoscopic Ultrasonography Guided Biliary Drainage and Percutaneous
      Transhepatic Biliary Drainage in the Management of Malignant Obstructive Jaundice
      After Failed ERCP.
AB  - AIMS: The aim of this study is to compare the efficacy and safety of endoscopic
      ultrasonography guided biliary drainage and percutaneous transhepatic biliary
      drainage in the management of malignant obstructive jaundice after failed ERCP.
      METHODS: We performed a prospective study on 66 consecutive patients with
      malignant obstructive jaundice admitted to our hospital between January 2014 and
      January 2016 [corrected]. Patients were performed endoscopic ultrasonography
      guided biliary drainage in 36 cases (group A) and percutaneous transhepatic
      biliary drainage in 30 cases (group B) according to the results of the draw. Data
      on the following variables were compared between the 2 groups: the technical
      success rate, the clinical success rate, complications, length of hospital stay,
      and hospital costs. RESULTS: There was statistically significant difference in
      the clinical success rate (88.89% vs. 66.67%; chi=4.84), complications (5.56% vs.
      23.33%; chi=4.39), length of hospital stay (11.54+/-3.73 d vs. 15.68+/-6.56 d;
      t=8.17) and hospital costs (23.52+/-8.44 thousand yuan vs. 32.81+/-6.06 thousand
      yuan; t=16.28) (P<0.05) between group A and group B. The technical success rate
      was higher in groups A than that in group B, although the difference did not
      reach statistical significance (94.44% vs. 86.67%; chi=1.20; P>0.05).
      CONCLUSIONS: In the treatment of malignant obstructive jaundice, endoscopic
      ultrasonography guided biliary drainage is safer and more effective than
      percutaneous transhepatic biliary drainage when performed by experienced
      practitioners after failed ERCP. Its more widespread use is recommended.

PMID- 29206805
TI  - Axial to Centrifugal Continuous Flow LVAD Pump Exchange Using Minimally Invasive
      Technique.
AB  - Driveline or device infection may complicate left ventricular assist device
      implants, and only curative option may be pump exchange. Replacement with similar
      device may be liable to reinfection, because pump configuration is such that the
      new device and driveline may partly lie within the pocket of the previous pump.
      One approach to overcome this is using a different pump design such that the new
      pump would lie in a different location from the old pump. We describe treatment
      of severe HeartMate II (Abbott, [St Jude Thoratec Corp], Pleasanton, CA USA) left
      ventricular assist device infection by minimally invasive exchange to an
      intrapericardial HVAD (HeartWare International, Inc, Framingham, MA USA) left
      ventricular assist device.

PMID- 29206806
TI  - Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry for
      Cyclosporine Analysis in Human Whole Blood and Comparison With an Antibody
      Conjugated Magnetic Immunoassay.
AB  - BACKGROUND: Various immunoassays have been used for cyclosporine A (CsA) analysis
      in human whole blood; however, they could not fully satisfy the requirements of
      criteria for accuracy and specificity in CsA measurement. The liquid
      chromatography tandem mass spectrometry is a gold method for CsA analysis. The
      aim of the study was to develop and validate an ultra-high performance liquid
      chromatography tandem mass spectrometry (UHPLC-MS/MS) method for CsA analysis and
      establish its agreement with an antibody-conjugated magnetic immunoassay (ACMIA)
      in clinical sample analysis. METHODS: An UHPLC-MS/MS method for CsA analysis in
      human whole blood was developed, validated, and applied in 85 samples, which were
      also tested by ACMIA. The agreement between UHPLC-MS/MS and ACMIA was evaluated
      by Bland-Altman plot. RESULTS: The calibration range was 5-2000 ng/mL. The
      inaccuracy and imprecision were -4.60% to 5.56% and less than 8.57%,
      respectively. The internal standard-normalized recovery and matrix factor were
      100.4%-110.5% and 93.5%-107.6%, respectively. The measurements of ACMIA and UHPLC
      MS/MS were strongly correlated (r > 0.98). Evaluated by Bland-Altman plot, the
      95% limit of agreement of the ACMIA:UHPLC-MS/MS ratio was 88.7%-165.6%, and the
      mean bias of the ratio was 21.1%. CONCLUSIONS: A rapid, simple, accurate, and
      reliable UHPLC-MS/MS method for CsA analysis in human whole blood was developed,
      validated, and applied in 85 samples. On average, 21.1% overestimation was
      observed in ACMIA compared with that in the UHPLC-MS/MS. Further and larger
      studies are required to identify whether this degree of variance could be
      accepted by clinicians.

PMID- 29206807
TI  - Comparison of the Arktm Immunoassay With Hplc-Uv for Therapeutic Drug Monitoring
      of Linezolid.
AB  - BACKGROUND: An enzymatic immunoassay is under development by ARK Diagnostics,
      Inc. for the quantification of plasma concentrations of linezolid (LZD). In the
      present study, the authors aimed to assess the performance of this immunoassay
      using a validated HPLC-UV method as reference. METHODS: Within- and between-day
      in vitro inaccuracy and imprecision of the ARK LZD assay were firstly tested
      using spiked quality controls (QC) provided by the kit manufacture. Subsequently,
      the performance of the immunoassay was verified in vivo by analyzing 170 trough
      LZD plasma samples from patients on antibiotic therapy. RESULTS: Imprecision of
      the spiked QCs resulted in every instance less than 7.0% and the inaccuracy
      ranged from -1.5% to 6.6%. The linear correlation between the two methods was
      documented by the Pearson analysis of plasma samples from patients on LZD therapy
      (coefficient = 0.9619). By Bland-Altman comparison, 8.2% of the patient samples
      resulted out of the limits ranging from -27.0% to +33.5%, with the large majority
      of them having LZD concentrations exceeding 10 mg/L. CONCLUSIONS: Acceptable
      analytical performance of the ARK LZD immunoassay has been demonstrated both with
      spiked QC and patients' samples, making it a viable alternative to HPLC for the
      TDM of LZD in clinical practice in laboratory hospitals that do not have HPLC
      equipment.

PMID- 29206808
TI  - Extrinsic Calcitonin Gene-Related Peptide Inhibits Hyperoxia-Induced Alveolar
      Epithelial Type II Cells Apoptosis, Oxidative Stress, and Reactive Oxygen Species
      (ROS) Production by Enhancing Notch 1 and Homocysteine-Induced Endoplasmic
      Reticulum Protein (HERP) Expression.
AB  - BACKGROUND Lung alveolar epithelial type II cells (AEC II) are the most important
      stem cells in lung tissues, which are critical for wound repair of
      bronchopulmonary dysplasia (BPD). This study investigated the effects of
      calcitonin gene-related peptide (CGRP) on AEC II cells exposed to hyperoxia.
      MATERIAL AND METHODS Neonatal rat AEC II cells were isolated and identified by
      detecting surfactant protein C (SP-C). Three small interfering RNAs targeting
      Notch 1 were synthesized and transfected into AEC II. A hyperoxia-exposed AEC II
      cell injury model was established and was divided into 8 groups. MDA levels and
      SOD activity were examined using lipid peroxidation assay kits. Apoptosis and
      reactive oxygen species (ROS) production were evaluated using flow cytometry.
      Notch 1 mRNA expression was examined using RT-PCR. Homocysteine-induced
      endoplasmic reticulum protein (HERP) was examined using Western blot analysis.
      RESULTS CGRP treatment significantly enhanced MDA levels and decreased SOD
      activity compared to hyperoxia-treated AEC II cells (P<0.05). CGRP treatment
      significantly inhibited hyperoxia-induced AEC II cell apoptosis, and
      significantly suppressed hyperoxia-induced ROS production compared to hyperoxia
      treated AEC II cells (P<0.05) either undergoing g secretase inhibitor or Notch
      RNA interference. CGRP significantly triggered Notch 1 mRNA expression and
      significantly enhanced HERP expression compared to hyperoxia-treated AEC II cells
      (P<0.05) either undergoing g secretase inhibitor or Notch RNA interference.
      CONCLUSIONS In AEC II cells, extrinsic peptide CGRP suppressed hyperoxia-induced
      apoptosis, oxidative stress, and ROS production, which may be triggered by Notch
      1 and HERP signaling pathway.

PMID- 29206809
TI  - Effect of recombinant human growth hormone therapy on blood lipid and carotid
      intima-media thickness in children with growth hormone deficiency.
AB  - BackgroundReports on the association between growth hormone deficiency (GHD) and
      cardiovascular risk factors in children are limited. We aim to investigate the
      effect of different doses of recombinant human growth hormone (rhGH) therapy on
      blood lipid and carotid intima-media thickness (cIMT) in Chinese GHD
      children.MethodsNinety children, including sixty isolated GHD children and thirty
      healthy children, were enrolled. GHD children were randomly divided into two
      groups (A and B) according to the rhGH dose given: group A received 0.23
      mg/kg/week and group B received 0.35 mg/kg/week for 12 months. The TC, TG, LDL-C,
      HDL-C, and cIMT at baseline and after treatment were measured.ResultsThe height,
      weight, and height velocity improved significantly over 12 months of rhGH therapy
      in all GHD children. At baseline, GHD children in both the treatment groups
      showed significantly higher total cholesterol (TC), triglyceride (TG), low
      density lipoprotein-cholesterol (LDL-C), cIMT, and lower high-density lipoprotein
      cholesterol (HDL-C) than healthy children (all P<=0.033). After the 12-month rhGH
      therapy, a significant decrease in the TC, TG, LDL-C, and cIMT, as well as a
      significant increase in the HDL-C (P<=0.046), was observed in the GHD children,
      with change in the group B being even more marked.ConclusionsThe RhGH replacement
      therapy in GHD children can improve both the blood lipid profile and carotid
      intima-media thickness, with higher-dose rhGH therapy showing superior effects.

PMID- 29206810
TI  - mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of
      Tuberous Sclerosis Complex.
AB  - Drugs targeting metabotropic glutamate receptor 5 (mGluR5) have therapeutic
      potential in autism spectrum disorders (ASD), including tuberous sclerosis
      complex (TSC). The question whether inhibition or potentiation of mGluR5 could be
      beneficial depends, among other factors, on the specific indication. To
      facilitate the development of mGluR5 treatment strategies, we tested the
      therapeutic utility of mGluR5 negative and positive allosteric modulators (an
      mGluR5 NAM and PAM) for TSC, using a mutant mouse model with neuronal loss of
      Tsc2 that demonstrates disease-related phenotypes, including behavioral symptoms
      of ASD and epilepsy. This model uniquely enables the in vivo characterization and
      rescue of the electrographic seizures associated with TSC. We demonstrate that
      inhibition of mGluR5 corrects hyperactivity, seizures, and elevated de novo
      synaptic protein synthesis. Conversely, positive allosteric modulation of mGluR5
      results in the exacerbation of hyperactivity and epileptic phenotypes. The data
      suggest a meaningful therapeutic potential for mGluR5 NAMs in TSC, which warrants
      clinical exploration and the continued development of mGluR5 therapies.

PMID- 29206812
TI  - When and How to Stop Surveillance Colonoscopy in Older Adults: Five Rules of
      Thumb for Practitioners.

PMID- 29206813
TI  - A Randomized Double-Blind, Placebo-Controlled, Cross-Over Study Using Baclofen in
      the Treatment of Rumination Syndrome.
AB  - OBJECTIVES: Both rumination syndrome and supra-gastric belching (SGB) have
      limited treatment options. We demonstrated (open-label) that baclofen reduces
      pressure flow events in these patients. We aimed to study the effect of baclofen
      in a placebo-controlled, double-blind, cross-over study in patients with
      clinically suspected rumination and/or SGB. METHODS: Twenty tertiary-care
      patients (mean age 42 years (range 18-61), 13f) with clinically suspected
      rumination and/or SGB were randomized to receive baclofen (10 mg, t.i.d) or
      placebo for 2 weeks with cross-over to the alternative intervention after a 1
      week wash-out period. At the end of each treatment period, patients underwent a
      solid-state high-resolution impedance manometry measurement, during which they
      registered symptoms. Patients received a solid meal and recordings continued for
      1 h. They scored overall treatment evaluation (OTE) on a -3 to +3 scale. RESULTS:
      Both the number of regurgitation event markers and rumination episodes were
      significantly decreased after baclofen (6 (0-19) vs. 4 (0-14), P=0.04; 13 (8-22)
      vs. 8 (3-11), P=0.004). The number of SGB episodes was similar in both groups.
      Lower esophageal sphincter (LES) pressure was significantly higher and the number
      of transient LES relaxations was significantly lower after baclofen (17.8 (12.7
      22.7) vs. 13.1 (7.2-16.9) mm Hg, P=0.0002; 4(1-8) vs. 7(3-12), P=0.17). The
      number of reflux events decreased in the baclofen condition (4 (1-9) vs. 3 (0-6),
      P=0.03). Straining episodes were similar in both arms, but the
      rumination/straining ratio was significantly lower in the baclofen arm (0.06 (0
      0.32) vs. 0.33 (0-0.51), P=0.0012). OTE was superior after baclofen compared to
      placebo (P=0.03). CONCLUSIONS: Baclofen is an effective treatment option for
      patients with rumination syndrome, probably through its effect on LES pressure.

PMID- 29206814
TI  - Expanding the Facebook Platform to Engage and Educate Online Communities.

PMID- 29206815
TI  - Novel Intra-Procedural Distensibility Measurement Accurately Predicts Immediate
      Outcome of Pneumatic Dilatation for Idiopathic Achalasia.
AB  - OBJECTIVES: Often 2-3 graduated pneumatic dilatations (PD) are required to treat
      achalasia as there is no current intra-procedural predictor of clinical response.
      Distensibility measurements using functional lumen imaging probe (FLIP) may
      provide an intra-procedural predictor of outcome. Our aim was to determine the
      optimal criterion for esophagogastric junction (EGJ) distensibility measurements
      during PD that predicts immediate clinical response. METHODS: EGJ distensibility
      was prospectively measured using FLIP immediately pre- and post-PD. The EGJ
      distensibility index (EGJ-DI) was defined as a ratio of the narrowest cross
      sectional area and the corresponding intra-bag pressure at 40 ml distension.
      Immediate and short-term clinical responses were defined as Eckardt score <=3
      assessed 2 weeks Post-PD and at 3-month follow-up, respectively. RESULTS: In 54
      patients, we performed thirty-seven 30 mm; twenty 35 mm and six 40 mm PDs. The
      short-term response rate to the graded PD was 93% (27/29) in newly diagnosed
      achalasia; 87% (13/15) and 70% (7/10) in those who had relapsed after previous PD
      and Heller's Myotomy, respectively. Among those demonstrating an immediate
      response, EGJ-DI increased by an average of 4.5 mm2/mmHg (95% CI (3.5, 5.5)
      (P<0.001). Within-subject Delta EGJ-DI was highly predictive of immediate
      clinical response with AUROC of 0.89 (95% CI [0.80, 0.98], P<0.001). An increment
      in EGJ-DI of 1.8 mm2/mmHg after a single PD predicts an immediate response with
      an accuracy of 87%. CONCLUSIONS: FLIP-measured Delta EGJ-DI is a novel intra
      procedural tool that accurately predicts immediate clinical response to PD in
      achalasia. This technique may potentially dictate an immediate mechanism to "step
      up" dilator size within a single endoscopy session.

PMID- 29206811
TI  - Neuronal Mechanisms for Sleep/Wake Regulation and Modulatory Drive.
AB  - Humans have been fascinated by sleep for millennia. After almost a century of
      scientific interrogation, significant progress has been made in understanding the
      neuronal regulation and functions of sleep. The application of new methods in
      neuroscience that enable the analysis of genetically defined neuronal circuits
      with unprecedented specificity and precision has been paramount in this endeavor.
      In this review, we first discuss electrophysiological and behavioral features of
      sleep/wake states and the principal neuronal populations involved in their
      regulation. Next, we describe the main modulatory drives of sleep and
      wakefulness, including homeostatic, circadian, and motivational processes.
      Finally, we describe a revised integrative model for sleep/wake regulation.

PMID- 29206816
TI  - Optimizing Selection of Biologics in Inflammatory Bowel Disease: Development of
      an Online Patient Decision Aid Using Conjoint Analysis.
AB  - OBJECTIVES: Recent drug approvals have increased the availability of biologic
      therapies for inflammatory bowel disease (IBD), making it difficult for patients
      with ulcerative colitis (UC) and Crohn's disease (CD) to navigate treatment
      options. Here we developed a conjoint analysis to examine patient decision-making
      surrounding biologic medicines for IBD. We used the results to create an online
      patient decision aid that generates a unique "preferences report" for each
      patient to assist with shared decision-making with their provider. METHODS: We
      administered an adaptive choice-based conjoint survey to IBD patients that
      quantifies the relative importance of biologic attributes (e.g., efficacy, side
      effect profile, mode of administration, and mechanism of action) in decision
      making. The conjoint software determined individual patient preferences by
      calculating part-worth utilities for each attribute. We conducted regression
      analyses to determine if demographic and disease characteristics (e.g., type of
      IBD and severity) predicted how patients made decisions. RESULTS: 640 patients
      completed the survey (UC=304; CD=336). In regression analyses, demographics and
      IBD characteristics did not predict individual patient preferences; the main
      exception was IBD type. When compared to UC, CD patients were more likely to
      report side effect profile as most important (odds ratio (OR) 1.63, 95%
      confidence interval (CI) 1.16-2.30). Conversely, those with UC were more likely
      to value therapeutic efficacy (OR 1.41, 95% CI 1.01-2.00). CONCLUSIONS: Biologic
      decision-making is highly personalized; demographic and disease characteristics
      poorly predict individual preferences, indicating that IBD patients are unique
      and difficult to statistically categorize. The online decision tool resulting
      from this study (www.ibdandme.org) may be used by patients to support shared
      decision-making and optimize personalized biologic selection with their provider.

PMID- 29206817
TI  - Quality of Care and the Irritable Bowel Syndrome: Is Now the Time to Set
      Standards?

PMID- 29206818
TI  - HCV Therapy in Decompensated Cirrhosis before or after Liver Transplantation: A
      Paradoxical Quandary.

PMID- 29206820
TI  - [General practitioner certification].
AB  - La regulacion de la profesion medica es un proceso antiguo en nuestro pais. Desde
      los tiempos del virreinato existia el Real Tribunal del Protomedicato, que tenia
      como funcion examinar a los medicos, cirujanos y boticarios para ser autorizados
      a ejercer su profesion; con el tiempo, esta funcion se fue relegando en otras
      estructuras administrativas que se fueron modificando, pero que la mantuvieron en
      vigor.

PMID- 29206819
TI  - Mechanisms of inactivation of the tumour suppressor gene RHOA in colorectal
      cancer.
AB  - BACKGROUND: Reduced RHOA signalling has been shown to increase the
      growth/metastatic potential of colorectal tumours. However, the mechanisms of
      inactivation of RHOA signalling in colon cancer have not been characterised.
      METHODS: A panel of colorectal cancer cell lines and large cohorts of primary
      tumours were used to investigate the expression and activity of RHOA, as well as
      the presence of RHOA mutations/deletions and promoter methylation affecting RHOA.
      Changes in RHOA expression were assessed by western blotting and qPCR after
      modulation of microRNAs, SMAD4 and c-MYC. RESULTS: We show here that RHOA point
      mutations and promoter hypermethylation do not significantly contribute to the
      large variability of RHOA expression observed among colorectal tumours. However,
      RHOA copy number loss was observed in 16% of colorectal tumours and this was
      associated with reduced RHOA expression. Moreover, we show that miR-200a/b/429
      downregulates RHOA in colorectal cancer cells. In addition, we found that TGF
      beta/SMAD4 upregulates the RHOA promoter. Conversely, RHOA expression is
      transcriptionally downregulated by canonical Wnt signalling through the Wnt
      target gene c-MYC that interferes with the binding of SP1 to the RHOA promoter in
      colon cancer cells. CONCLUSIONS: We demonstrate a complex pattern of inactivation
      of the tumour suppressor gene RHOA in colon cancer cells through genetic,
      transcriptional and post-transcriptional mechanisms.

PMID- 29206821
TI  - [Analysis of road traffic injuries in Mexican cyclists].
AB  - With the objective of analyzing fatal and non-fatal road traffic injuries in
      cyclists and to document helmet use in this road user to inform sustainable
      mobility policies, a descriptive analysis of four secondary official information
      sources was conducted at the national level: mortality, Ministry of Health's
      hospital discharges, Unintentional and Violence Registry System (SIS-SS-17-P) and
      the 2012 National Health and Nutrition Survey (ENSANUT). Only SIS-SS-17-P and
      ENSANUT document helmet use. Except for ENSANUT information analyzed is of 2014.A
      total of 190 cyclists died in Mexico during 2014 and 392 were hospitalized; head
      was the anatomical region most frequently affected (63% and 32%, respectively).
      Only 0.75% of the 667 cases registered in SIS-17 reported helmet use and 24%
      suffered head injuries. Of the 165,348 non-fatally injured cyclists from ENSANUT
      <10% used helmet, 24% had head injuries and more than 16,000 suffered permanent
      injuries. Whereas cyclist-friendly infrastructure is an effective intervention to
      prevent injuries in the long term, helmet use could potentially reduce the
      frequency and severity of head injuries in the short run while bicycle use
      widespread as a means of transportation providing "safety in numbers".

PMID- 29206822
TI  - Analysis of accidents and injuries on motorcycles in Mexico.
AB  - OBJECTIVE: To analyze the type of injuries and the characteristics and
      geographical distribution of road accidents where motorcycles were involved in
      Mexico. METHODS: A descriptive analysis of second-hand information sources was
      conducted, including the number of accidents (N = 41,881), total number of
      injured people (N = 13,916) and medical expenses (N = 9,111) associated to
      motorcycle accidents during 2014. RESULTS: Motorcycles represent 13.14% of the
      total number of deaths in road accidents in Mexico, and the Southeast region of
      Mexico registers the highest proportion of fatal injuries. Of the total number of
      motorcycles, 1.84% (95% confidence interval [CI]: 1.83-1.86) were involved in a
      collision. 3.64 (95% CI: 3.39-3.89) people died and 105.5 (95% CI: 104.1-106.8)
      were injured in every 10,000. Out of the total number of injuries, 76.6% were
      male and 53.74% were women. 55.1% of deaths were caused by intracranial trauma.
      Only 16.6% wore a helmet at the time of the accident, and those not wearing a
      helmet had a 2.11 (odds ratio [OR]: 2.1; CI 95%: 1.8-2.4) higher chance of head
      injury. Regarding the severity of the crash, those occurred in suburban areas
      (OR: 6.58; CI 95%: 5.69-7.60), in unpaved surfaces (OR: 4.13; CI 95%: 3.04-5.61),
      after low alcohol consumption (OR: 1.89; CI 95%: 1.46-2.44), at night (OR: 2.24;
      CI 95%: 1.95-2.57) and on weekends (OR: 1.65; CI 95%: 1.44-1.90), had the highest
      chance of turning into a fatal accident. CONCLUSIONS: In spite of the progress
      made in terms of road safety, motorcycle accidents are still increasing, and the
      use of a helmet is still proportionally low. More information on these groups and
      risk factors needs to be available so people are better informed. Also,
      regulations need improvements regarding the use of security equipment like
      helmets in order to reduce injuries and fatal accidents.

PMID- 29206823
TI  - [Thoracic and lumbar fractures in adolescents. An eight-year study].
AB  - METHODS: In order to know the characteristics of these lesions in our environment
      and compare with those the adults, a transversal and descriptive study of
      adolescents between 12 and 18 years who were hospitalized for thoracic and lumbar
      fracture in two centers of high level trauma in our country for 8 years was
      performed. The variables studied were applied statistical analysis descriptive
      and correlation. RESULTS: They were found significant date by associating the
      causes of damage with associated lesions (p = 0.006) and the initial neurological
      damage associated with the final neurological damage (p = 0.000). DISCUSSION:
      They were registered seven teenagers with 10 fractures firearm, as rare cause of
      injury. An increase in the frequency of thoracic and lumbar fractures in
      adolescents with increasing age was found. The thoracic and lumbar fractures in
      adolescents caused by road accidents are associated with lesions in the chest and
      abdomen. And when are caused by falls are associated with lower extremity
      fractures. In addition, 13.5% of cases showed significant changes toward
      improvement in the initial neurological damage.

PMID- 29206824
TI  - [Approach to percutaneous nephrolithotomy. Comparison of the procedure in a one
      shot versus the sequential with metal dilata].
AB  - INTRODUCTION: Percutaneous nephrolithotomy is an efficient approach for treatment
      of different types of kidney stones. Various types of access techniques have been
      described like sequential dilatation and one-shot procedure. OBJECTIVE: To
      determine the differences in time of exposure to X-rays and hemoglobin levels
      between techniques. METHODS: Controlled clinical trial. Patients older than 18
      years with complex/uncomplicated kidney stones, without urine infection were
      included. They were assigned randomly to one of the two techniques. Response
      variables were determined before and 24 h after procedures. RESULTS: 59 patients
      were included: 30 underwent one-shot procedure (study-group) and 29 sequential
      dilatation (control-group). Baseline characteristics were similar. Study group
      had a lower postoperative hemoglobin decline than control group (0.81 vs. 2.03
      g/dl, respectively; p < 0.001); X-ray exposure time (69.6 vs. 100.62 s; p <
      0.001) and postoperative creatinine serum levels (0.93 +/- 0.29 vs. 1.13 +/- 0.4
      mg/dl; p = 0.039). No significant differences in postoperative morbidity were
      found. CONCLUSION: One-shot technique demonstrated better results compared to
      sequential dilatation.

PMID- 29206825
TI  - Clinical competence of Guatemalan and Mexican physicians for family dysfunction
      management.
AB  - OBJECTIVE: To evaluate the clinical competence of Mexican and Guatemalan
      physicians to management the family dysfunction. METHODS: Cross comparative study
      in four care units first in Guadalajara, Mexico, and four in Guatemala,
      Guatemala, based on a purposeful sampling, involving 117 and 100 physicians,
      respectively. Clinical competence evaluated by validated instrument integrated
      for 187 items. Non-parametric descriptive and inferential statistical analysis
      was performed. RESULTS: The percentage of Mexican physicians with high clinical
      competence was 13.7%, medium 53%, low 24.8% and defined by random 8.5%. For the
      Guatemalan physicians'14% was high, average 63%, and 23% defined by random. There
      were no statistically significant differences between healthcare country units,
      but between the medium of Mexicans (0.55) and Guatemalans (0.55) (p = 0.02).
      CONCLUSION: The proportion of the high clinical competency of Mexican physicians'
      was as Guatemalans.

PMID- 29206826
TI  - [Response to serotonergic and noradrenergic antidepressants: a crossover study of
      fluoxetine and desipramine in patients with first major depression episode].
AB  - BACKGROUND: Response rate data from studies with different kinds of
      antidepressant drugs help in the development of guidelines for the rational
      prescription of pharmacotherapy. However, there are still few comparative studies
      with selective reuptake inhibition on serotonin or norepinephrine in the same
      sample of major depression patients. METHODS: First episode major depression (DSM
      III-R) outpatients who completed 6 weeks in two double-blind randomized trials
      with fluoxetine and desipramine were crossed over to treatment with the other
      drug under open conditions for 6 weeks. Response was considered if patient's
      final Hamilton depression scale score decreased 50% or more from baseline.
      RESULTS: No significant differences were found by drug treatment or sequence of
      treatment. Ten of the 18 patients (55.5%) were responders to both fluoxetine and
      desipramine, 3 (16.6%) were resistant to fluoxetine, 3 (16.6%) to desipramine and
      2 (11.1%) to both drugs. DISCUSSION: These data suggest that among first major
      depressive episode outpatients fluoxetine and desipramine are equally effective.
      In patients who have been non-responders to one of the studied drugs, the other
      one is strikingly effective; this kind of treatment maneuver should be considered
      in such patients.

PMID- 29206827
TI  - [Health obligation or health fascism].
AB  - El Dr. Lifshitz presenta un editorial interesante sobre la campana de una region
      de Italia que pretendia que la salud debia ser obligatoria y que quien no la
      obedeciera tendria pena de muerte. Esta pretension, que de entrada resulta
      simpatica, quiza muestra la desesperacion de un sistema de salud que se ve
      rebasado presupuestalmente con el incremento de la esperanza de vida y, por ende,
      de la presentacion de enfermedades cronicas degenerativas en la poblacion.

PMID- 29206828
TI  - Chest trauma of Alexander the Great, a pneumology approach.
AB  - Delgado-Garcia, et al. presentan una disertacion amplia, con revision historica
      profunda, de la lesion toracica que sufrio Alejandro Magno por el disparo de una
      saeta de dos codos de largo (88 cm) en la batalla contra los malios, donde a
      traves de diversas narraciones se ha considerado que sufrio un neumotorax y que
      debido a la gravedad de la lesion sus medicos decidieron retirar el objeto
      punzocortante, obteniendose aire y sangre posextraccion; el emperador perdio el
      estado de alerta, recuperandose posteriormente la herida y permitiendole montar a
      caballo a los pocos dias. Los autores finalizan con la frase "Lo sucedido despues
      del flechazo torna inverosimil la posibilidad de un neumotorax".

PMID- 29206829
TI  - [Transition from Millennium Development Goals to Sustainable Development Goals
      from the perspective of the social determinants of health and health equity].
AB  - The United Nations Declaration of 2000 agreed on eight millennium development
      goals (MDGs) to be met in 2015. The results show that poverty continues through
      population growth and advances in both rich and poor countries are threatened by
      economic crises and inequities in geographic areas and population groups within
      countries. In a globalized world with great social and economic inequalities,
      from the perspective of the social determinants of health (SDH), the relevance of
      the new 17 sustainable development goals (SDGs) is greater. Faced with the health
      challenges in our country to achieve SDGs, the symposium "The transition from
      MDGs to SDGs from the perspective of SDH and health equity" was presented at the
      XLIV Congress of the National Academy of Medicine. The presentations dealt with
      five important aspects of the transition in Mexico: background and context; the
      current state of the MDGs in childhood; the impact on gender equity and
      adolescent fertility; the health system and the theme of environmental health and
      were presented by Dr. Raffaela Schiavon, Jacobo Finkelman, Luis Jasso and Rafael
      Lozano.

PMID- 29206830
TI  - [The masters of thoracic trauma in the Central Hospital of the Mexican Red Cross.
      Their story and legacy].
AB  - The branches of medicine responsible for the care of victims of different types
      of injuries were born as a result of the urgent need to save lives during the
      wars. In Mexico, one of the first hospitals developed for the care of injured
      patients was the Central Hospital of the Mexican Red Cross. The aim of this
      article is to pay tribute to the first service for the care of patients with
      chest trauma, founded in 1954, its founders and those who have continued with
      their work: Dr. Pedro Garza Alegria, Dr. Octavio Rivas Solis Dr. Jesus Genis
      Becerra, etc. In 64 years of existence, there have been trained eight specialists
      in cardiothoracic surgery and three of them have worked in the Central Hospital
      of the Mexican Red Cross.

PMID- 29206831
TI  - Prognostic value of ALDH2 polymorphism for patients with oropharyngeal cancer in
      a Japanese population.
AB  - BACKGROUND: Half of Japanese possess a polymorphism of aldehyde dehydrogenase
      2(ALDH2), while few white individuals possess this mutation. The purpose of this
      study was to investigate the possibility of ALDH2 polymorphism as a prognostic
      factor for oropharyngeal cancer (OPC) among Japanese population. METHODS: We
      analyzed 82 Japanese patients with OPC treated between 2006 and 2011. The median
      observation period was 50 months. P16-staining and ALDH2 polymorphisms were
      investigated. To examine the frequencies of second primary pharyngeal and
      esophageal cancers (SPPEC),37 Japanese patients with OPC treated at Tokyo
      University Hospital were included for statistical analysis. RESULTS:
      Statistically significant differences were noted in OS among sex, age, N
      classification, and p16 (p = 0.045, 0.024, 0.020, 0.007, respectively). In
      addition, OS and DSS rates of the patients with heterozygous ALDH2 tended to be
      worse than those of the patients with homozygous ALDH2 (p = 0.21, 0.086,
      respectively). Of note, OS and DSS of the patients with p16-negative OPC and
      heterozygous ALDH2 was significant poorer than those of the patients with p16
      positive OPC (p = 0.002, 0.006, respectively), while there was no significant
      difference in OS and DSS between patients with p16-positive OPC and patients with
      p16-negative OPC and homozygous ALDH2. CONCLUSIONS: ALDH2 polymorphism might be a
      promising prognostic factor for Japanese patients with p16-negative OPC.

PMID- 29206832
TI  - The effects of dipeptidyl peptidase-4 inhibitors on bone fracture among patients
      with type 2 diabetes mellitus: A network meta-analysis of randomized controlled
      trials.
AB  - AIM: The association between dipeptidyl peptidase-4 inhibitors (DPP-4is), a class
      of anti-diabetes, and bone fracture in patients with type 2 diabetes mellitus
      (T2DM) is unknown. This meta-analysis aimed to systematically evaluate the
      effects of DPP-4is on bone fracture in T2DM patients. METHODS: We searched the
      Cochrane Library, Embase, Medline and ClinicalTrials.gov from inception through
      April 28th, 2016 to identify randomized controlled trials (RCTs) that compared
      DPP-4is with placebo or other anti-diabetes in T2DM patients. RCTs lasting more
      than 12 weeks and having data on bone fracture were included. We conducted random
      effects meta-analysis to estimate odds ratios (ORs) and their 95% confidence
      intervals (CIs), and network meta-analysis (NMA) to supplement direct
      comparisons. Predictive interval plot and node-splitting method were used to
      evaluate the heterogeneity and inconsistency for NMA, while the funnel plot was
      applied to explore publication bias. Besides, study quality was assessed
      according to Cochrane risk of bias tool. RESULTS: We identified 75 RCTs with a
      total of 70,207 patients and 11 treatments: interventions included 5 DPP-4is
      (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin), while controls
      included placebo and 5 other anti-diabetes (sulfonylureas, glucagon-like peptide
      1 receptor agonists, metformin, thiazolidinediones, sodium-glucose co-transporter
      2 inhibitors). In the NMA, the risk of fracture for alogliptin tended to decrease
      when versus placebo (OR, 0.51; 95% CI, 0.29 to 0.88). Besides, aloglitpin had a
      lower risk compared with linagliptin (OR, 0.45; 95% CI, 0.20 to 0.99) and
      saxagliption (OR, 0.46; 95%CI, 0.25 to 0.84); the risk was higher with
      saxagliptin when versus sitagliptin (OR, 1.90; 95% CI, 1.04 to 3.47) and
      sulfonylureas (OR, 1.98; 95% CI, 1.06 to 3.71). In the direct pairwise meta
      analysis, alogliptin was associated with a non-significant tendency to reduction
      of bone fracture compared with placebo (OR, 0.54; 95% CI, 0.29 to 1.01). Ranking
      probability analysis indicated alogliptin decreased the risk of bone fracture
      most with a probability of 76.3%. CONCLUSION: Alogliptin may be associated with a
      lower risk of bone fracture compared with placebo, linagliptin, or saxagliptin,
      while other anti-diabetes did not seem to have an association with the risk of
      bone fracture.

PMID- 29206833
TI  - Effects of women's groups practising participatory learning and action on
      preventive and care-seeking behaviours to reduce neonatal mortality: A meta
      analysis of cluster-randomised trials.
AB  - BACKGROUND: The World Health Organization recommends participatory learning and
      action (PLA) in women's groups to improve maternal and newborn health,
      particularly in rural settings with low access to health services. There have
      been calls to understand the pathways through which this community intervention
      may affect neonatal mortality. We examined the effect of women's groups on key
      antenatal, delivery, and postnatal behaviours in order to understand pathways to
      mortality reduction. METHODS AND FINDINGS: We conducted a meta-analysis using
      data from 7 cluster-randomised controlled trials that took place between 2001 and
      2012 in rural India (2 trials), urban India (1 trial), rural Bangladesh (2
      trials), rural Nepal (1 trial), and rural Malawi (1 trial), with the number of
      participants ranging between 6,125 and 29,901 live births. Behavioural outcomes
      included appropriate antenatal care, facility delivery, use of a safe delivery
      kit, hand washing by the birth attendant prior to delivery, use of a sterilised
      instrument to cut the umbilical cord, immediate wrapping of the newborn after
      delivery, delayed bathing of the newborn, early initiation of breastfeeding, and
      exclusive breastfeeding. We used 2-stage meta-analysis techniques to estimate the
      effect of the women's group intervention on behavioural outcomes. In the first
      stage, we used random effects models with individual patient data to assess the
      effect of groups on outcomes separately for the different trials. In the second
      stage of the meta-analysis, random effects models were applied using summary
      level estimates calculated in the first stage of the analysis. To determine
      whether behaviour change was related to group attendance, we used random effects
      models to assess associations between outcomes and the following categories of
      group attendance and allocation: women attending a group and allocated to the
      intervention arm; women not attending a group but allocated to the intervention
      arm; and women allocated to the control arm. Overall, women's groups practising
      PLA improved behaviours during and after home deliveries, including the use of
      safe delivery kits (odds ratio [OR] 2.92, 95% CI 2.02-4.22; I2 = 63.7%, 95% CI
      4.4%-86.2%), use of a sterile blade to cut the umbilical cord (1.88, 1.25-2.82;
      67.6%, 16.1%-87.5%), birth attendant washing hands prior to delivery (1.87, 1.19
      2.95; 79%, 53.8%-90.4%), delayed bathing of the newborn for at least 24 hours
      (1.47, 1.09-1.99; 68.0%, 29.2%-85.6%), and wrapping the newborn within 10 minutes
      of delivery (1.27, 1.02-1.60; 0.0%, 0%-79.2%). Effects were partly dependent on
      the proportion of pregnant women attending groups. We did not find evidence of
      effects on uptake of antenatal care (OR 1.03, 95% CI 0.77-1.38; I2 = 86.3%, 95%
      CI 73.8%-92.8%), facility delivery (1.02, 0.93-1.12; 21.4%, 0%-65.8%), initiating
      breastfeeding within 1 hour (1.08, 0.85-1.39; 76.6%, 50.9%-88.8%), or exclusive
      breastfeeding for 6 weeks after delivery (1.18, 0.93-1.48; 72.9%, 37.8%-88.2%).
      The main limitation of our analysis is the high degree of heterogeneity for
      effects on most behaviours, possibly due to the limited number of trials
      involving women's groups and context-specific effects. CONCLUSIONS: This meta
      analysis suggests that women's groups practising PLA improve key behaviours on
      the pathway to neonatal mortality, with the strongest evidence for home care
      behaviours and practices during home deliveries. A lack of consistency in
      improved behaviours across all trials may reflect differences in local
      priorities, capabilities, and the responsiveness of health services. Future
      research could address the mechanisms behind how PLA improves survival, in order
      to adapt this method to improve maternal and newborn health in different
      contexts, as well as improve other outcomes across the continuum of care for
      women, children, and adolescents.

PMID- 29206834
TI  - Influence of socioeconomic status on the whole blood transcriptome in African
      Americans.
AB  - BACKGROUND: The correlation between low socioeconomic status (SES) and poor
      health outcome or higher risk of disease has been consistently reported by many
      epidemiological studies across various race/ancestry groups. However, the
      biological mechanisms linking low SES to disease and/or disease risk factors are
      not well understood and remain relatively under-studied. The analysis of the
      blood transcriptome is a promising window for elucidating how social and
      environmental factors influence the molecular networks governing health and
      disease. To further define the mechanistic pathways between social determinants
      and health, this study examined the impact of SES on the blood transcriptome in a
      sample of African-Americans. METHODS: An integrative approach leveraging three
      complementary methods (Weighted Gene Co-expression Network Analysis, Random
      Forest and Differential Expression) was adopted to identify the most predictive
      and robust transcriptome pathways associated with SES. We analyzed the expression
      of 15079 genes (RNA-seq) from whole blood across 36 samples. RESULTS: The results
      revealed a cluster of 141 co-expressed genes over-expressed in the low SES group.
      Three pro-inflammatory pathways (IL-8 Signaling, NF-kappaB Signaling and
      Dendritic Cell Maturation) are activated in this module and over-expressed in low
      SES. Random Forest analysis revealed 55 of the 141 genes that, collectively,
      predict SES with an area under the curve of 0.85. One third of the 141 genes are
      significantly over-expressed in the low SES group. CONCLUSION: Lower SES has
      consistently been linked to many social and environmental conditions acting as
      stressors and known to be correlated with vulnerability to chronic illnesses
      (e.g. asthma, diabetes) associated with a chronic inflammatory state. Our
      unbiased analysis of the blood transcriptome in African-Americans revealed
      evidence of a robust molecular signature of increased inflammation associated
      with low SES. The results provide a plausible link between the social factors and
      chronic inflammation.

PMID- 29206835
TI  - The human kidney capsule contains a functionally distinct mesenchymal stromal
      cell population.
AB  - We recently demonstrated that the adult human kidney cortex contains a
      perivascular stromal cell (kPSC) that shows organotypic properties and is
      important for repair and stabilisation of kidney function. Not only the kidney
      cortex but also the kidney capsule contains stromal cells that are important for
      the three dimensional organisation of the kidney during nephrogenesis. They
      provide the barrier function of the capsule which is critical for homeostatic
      processes such as pressure natriuresis. We postulated that stromal cells derived
      from the kidney capsule may therefore also have specific properties and
      functions. To this end, we isolated these capsule mesenchymal stromal cells
      (cMSC) from human cadaveric kidneys that were not suitable for transplantation.
      There were several similarities between cMSCs and kPSCs including support of
      vascular plexus formation, phenotypic marker expression and resistance against
      myofibroblast transformation. However, compared to kPSCs, cMSCs showed distinct
      mRNA and miRNA expression profiles, showed increased immunosuppressive capacity,
      and displayed strongly reduced HGF production, contributing to the inability to
      enhance kidney epithelial repair. Therefore cMSCs are a distinct, novel human
      kidney-derived MSC-population and these data underpin the large functional
      diversity of phenotypic similar stromal cells in relation to their anatomic site,
      even within one organ.

PMID- 29206836
TI  - Where should the safe limits of alcohol consumption stand in light of liver
      enzyme abnormalities in alcohol consumers?
AB  - OBJECTIVES: To estimate the prevalence and risk factors for abnormal liver
      enzymes in a large age- and gender stratified population-based sample of
      apparently healthy individuals with or without alcohol consumption and other
      health-related risk factors (adiposity, physical inactivity, smoking). METHODS:
      Data on alcohol use, smoking, diet and physical activity were recorded using
      structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25-74
      years) in the national FINRISK studies. Alcohol data was used to categorize the
      participants into abstainers, light drinkers, moderate drinkers and heavy
      drinkers. Serum gamma-glutamyltransferase (GGT) and alanine aminotransferase
      (ALT) activities were measured using standard kinetic methods. RESULTS: Male
      light drinkers, moderate drinkers and heavy drinkers showed significantly higher
      relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval
      1.11 to 1.71, p < 0.01), 2.72 (2.08 to 3.56, p < 0.0005), and 6.10 (4.55 to 7.17,
      p < 0.0005), respectively. Corresponding values for women were 1.22 (0.99 to
      1.51, p = 0.065), 1.90 (1.44 to 2.51, p < 0.0005), and 5.91 (3.80 to 9.17, p <
      0.0005). Estimated threshold doses for a significant GGT elevation was 14
      standard weekly alcohol doses for men and 7 for women. Excess body weight and age
      over 40 years modulated the thresholds towards smaller quantities of alcohol. The
      risk of abnormal GGT was also significantly influenced by physical inactivity and
      smoking. The relative risks of abnormal ALT activities were increased in male
      heavy drinkers, especially in those presenting with adiposity and sedentary
      lifestyle. CONCLUSIONS: Alcohol use markedly increases the risk for abnormal
      liver enzyme activities in those presenting with age over 40 years, obesity,
      smoking or sedentary lifestyle. The data should be considered in public health
      recommendations and in the definitions of safe limits of alcohol use.

PMID- 29206837
TI  - Pyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes.
AB  - BACKGROUND: The incidence of pyogenic vertebral osteomyelitis (PVO) has increased
      over the past two decades. One possible cause of this increase is the aging of
      the population, which results in more comorbidities in high income countries.
      OBJECTIVE: To better characterize the clinical presentation and outcome of PVO in
      the elderly. DESIGN: We conducted a post-hoc analysis of a previously published
      trial that studied treatment duration in PVO and compared the presentation and
      outcomes according to age. PARTICIPANTS: Our analysis included 351 patients among
      whom 85 (24%) were 75-years-old or more. RESULTS: There were no significant
      differences in the socio-demographics of the patients. Neoplasia and chronic
      inflammatory diseases were more common in the older group: 34% vs. 19% (p =
      0.021) and 9% versus 1% (p = 0.004), respectively. There were no significant
      differences in clinical and radiological presentations between the groups in
      terms of back pain (337/351, 97%), fever (182/351, 52%), PVO localization,
      neurological signs and epidural abscess. Associated infective endocarditis (IE)
      was more frequent in the older group (37% vs. 14%, p<0.001). Streptococci were
      more frequently involved in infections of older patients (29% vs. 14%, p = 0.003)
      in contrast to Staphylococcus aureus (31% vs. 45%, p = 0.03). Older patients
      displayed higher mortality rates at 1 year (21% vs. 3%, p<0.001) and more adverse
      events related to cardiorespiratory failure (10.6% vs. 3.8%, p = 0.025), but had
      similar quality of life among the survivors. CONCLUSION: During PVO, the clinical
      and radiological findings are similar in older patients. Global mortality rates
      are higher in older patients compared to younger patients, which could be
      explained by the increased frequency of neoplasia at diagnosis and higher
      prevalence of associated IE in the elderly.

PMID- 29206838
TI  - Implementation of stroke teams and simulation training shortened process times in
      a regional stroke network-A network-wide prospective trial.
AB  - BACKGROUND: To meet the requirements imposed by the time-dependency of acute
      stroke therapies, it is necessary 1) to initiate structural and cultural changes
      in the breadth of stroke-ready hospitals and 2) to find new ways to train the
      personnel treating patients with acute stroke. We aimed to implement and validate
      a composite intervention of a stroke team algorithm and simulation-based stroke
      team training as an effective quality initiative in our regional
      interdisciplinary neurovascular network consisting of 7 stroke units. METHODS: We
      recorded door-to-needle times of all consecutive stroke patients receiving
      thrombolysis at seven stroke units for 3 months before and after a 2 month
      intervention which included setting up a team-based stroke workflow at each
      stroke unit, a train-the-trainer seminar for stroke team simulation training and
      a stroke team simulation training session at each hospital as well as a
      recommendation to take up regular stroke team trainings. RESULTS: The
      intervention reduced the network-wide median door-to-needle time by 12 minutes
      from 43,0 (IQR 29,8-60,0, n = 122) to 31,0 (IQR 24,0-42,0, n = 112) minutes (p <
      0.001) and substantially increased the share of patients receiving thrombolysis
      within 30 minutes of hospital arrival from 41.5% to 59.6% (p < 0.001). Stroke
      team training participants stated a significant increase in knowledge on the
      topic of acute stroke care and in the perception of patient safety. The overall
      course concept was regarded as highly useful by most participants from different
      professional backgrounds. CONCLUSIONS: The composite intervention of a binding
      team-based algorithm and stroke team simulation training showed to be well
      transferable in our regional stroke network. We provide suggestions and materials
      for similar campaigns in other stroke networks.

PMID- 29206839
TI  - Development of an organ failure score in acute liver failure for transplant
      selection and identification of patients at high risk of futility.
AB  - INTRODUCTION: King's College Hospital criteria are currently used to select liver
      transplant candidates in acetaminophen-related acute liver failure (ALF).
      Although widely accepted, they show a poor sensitivity in predicting pre
      transplant mortality and cannot predict the outcome after surgery. In this study
      we aimed to develop a new prognostic score that can allow patient selection for
      liver transplantation more appropriately and identify patients at high risk of
      futile transplantation. METHODS: We analysed consecutive patients admitted to the
      Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory
      data at admission were collected. Predictors of 3-month mortality in the non
      transplanted patients admitted to the Royal Free Hospital were used to develop
      the new score, which was then validated against the Beaujon cohort. The Beaujon
      transplanted group was also used to assess the ability of the new score in
      identifying patients at high risk of transplant futility. RESULTS: 152 patients
      were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores
      were the best predictors of 3-month mortality among non-transplanted patients.
      CLIF-C OF score and high dosages of norepinephrine requirement were the only
      significant predictors of 3-month mortality in the non-transplanted patients, and
      therefore were included in the ALF-OFs score. In non-transplanted patients, ALF
      OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%;
      specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%;
      specificity = 92.3%). ALF-OFs score was also able to identify patients at high
      risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity =
      79.2%). CONCLUSION: ALF-OFs is a new prognostic score in acetaminophen-related
      ALF that can predict both the need for liver transplant and high risk of
      transplant futility, improving candidate selection for liver transplantation.

PMID- 29206840
TI  - Age-related changes in somatic condition and reproduction in the Eurasian beaver:
      Resource history influences onset of reproductive senescence.
AB  - Using 15 years of data from a stable population of wild Eurasian beavers (Castor
      fiber), we examine how annual and lifetime access to food resources affect
      individual age-related changes in reproduction and somatic condition. We found an
      age-related decline in annual maternal reproductive output, after a peak at age 5
      6. Rainfall, an established negative proxy of annual resource availability for
      beavers, was consistently associated with lower reproductive output for females
      of all ages. In contrast, breeding territory quality, as a measure of local
      resource history over reproductive lifetimes, caused differences in individual
      patterns of reproductive senescence; animals from lower quality territories
      senesced when younger. Litter size was unrelated to maternal age, although adult
      body weight increased with age. In terms of resource effects, in poorer years but
      not in better years, older mothers produced larger offspring than did younger
      mothers, giving support to the constraint theory. Overall, our findings exemplify
      state-dependent life-history strategies, supporting an effect of resources on
      reproductive senescence, where cumulative differences in resource access, and not
      just reproductive strategy, mediate long-term reproductive trade-offs, consistent
      with the disposable soma and reproductive restraint theories. We propose that
      flexible life-history schedules could play a role in the dynamics of populations
      exhibiting reproductive skew, with earlier breeding opportunities leading to an
      earlier senescence schedule through resource dependent mechanisms.

PMID- 29206841
TI  - Auditory word recognition of verbs: Effects of verb argument structure on
      referent identification.
AB  - Word recognition includes the activation of a range of syntactic and semantic
      knowledge that is relevant to language interpretation and reference. Here we
      explored whether or not the number of arguments a verb takes impinges negatively
      on verb processing time. In this study, three experiments compared the dynamics
      of spoken word recognition for verbs with different preferred argument structure.
      Listeners' eye movements were recorded as they searched an array of pictures in
      response to hearing a verb. Results were similar in all the experiments. The time
      to identify the referent increased as a function of the number of arguments,
      above and beyond any effects of label appropriateness (and other controlled
      variables, such as letter, phoneme and syllable length, phonological
      neighborhood, oral and written lexical frequencies, imageability and rated age of
      acquisition). The findings indicate that the number of arguments a verb takes,
      influences referent identification during spoken word recognition.
      Representational complexity and amount of information generated by the lexical
      item that aids target identification are discussed as possible sources of this
      finding.

PMID- 29206842
TI  - From menarche to menopause: A population-based assessment of water, sanitation,
      and hygiene risk factors for reproductive tract infection symptoms over life
      stages in rural girls and women in India.
AB  - Women face greater challenges than men in accessing water, sanitation, and
      hygiene (WASH) resources to address their daily needs, and may respond to these
      challenges by adopting unsafe practices that increase the risk of reproductive
      tract infections (RTIs). WASH practices may change as women transition through
      socially-defined life stage experiences, like marriage and pregnancy. Thus, the
      relationship between WASH practices and RTIs might vary across female
      reproductive life stages. This cross-sectional study assessed the relationship
      between WASH exposures and self-reported RTI symptoms in 3,952 girls and women
      from two rural districts in India, and tested whether social exposures
      represented by reproductive life stage was an effect modifier of associations. In
      fully adjusted models, RTI symptoms were less common in women using a latrine
      without water for defecation versus open defecation (Odds Ratio (OR) = 0.69;
      Confidence Interval (CI) = 0.48, 0.98) and those walking shorter distances to a
      bathing location (OR = 0.79, CI = 0.63, 0.99), but there was no association
      between using a latrine with a water source and RTIs versus open defecation (OR =
      1.09; CI = 0.69, 1.72). Unexpectedly, RTI symptoms were more common for women
      bathing daily with soap (OR = 6.55, CI = 3.60, 11.94) and for women washing their
      hands after defecation with soap (OR = 10.27; CI = 5.53, 19.08) or ash/soil/mud
      (OR = 6.02; CI = 3.07, 11.77) versus water only or no hand washing. WASH
      practices of girls and women varied across reproductive life stages, but the
      associations between WASH practices and RTI symptoms were not moderated by or
      confounded by life stage status. This study provides new evidence that WASH
      access and practices are associated with self-reported reproductive tract
      infection symptoms in rural Indian girls and women from different reproductive
      life stages. However, the counterintuitive directions of effect for soap use
      highlights that causality and mechanisms of effect cannot be inferred from this
      study design. Future research is needed to understand whether improvements in
      water and sanitation access could improve the practice of safe hygiene behaviors
      and reduce the global burden of RTIs in women.

PMID- 29206843
TI  - Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues.
AB  - The periparturient period of dairy cows is characterized by intense lipolysis in
      adipose tissues (AT), which induces the release of free fatty acids (FFA) into
      circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation
      and can modulate inflammatory responses during lipolysis within AT. Linoleic and
      arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic
      acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified
      as products of lipolysis that could modulate AT inflammation during lipolysis.
      However, the effect of lipolysis intensity during the transition from gestation
      to lactation on fatty acid substrate availability and subsequent AT oxylipid
      biosynthesis is currently unknown. We hypothesized that in periparturient dairy
      cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide
      with changes in lipolysis intensity and stage of lactation. Blood and
      subcutaneous AT samples were collected from periparturient cows at -27+/-7 (G1)
      and -10+/-5 (G2) d prepartum and at 8+/-3 d postpartum (PP). Targeted lipidomic
      analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA
      concentrations increased as parturition approached and were highest at PP. Cows
      exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition
      scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L).
      Concentrations of plasma linoleic and arachidonic acids were increased at PP. In
      AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2.
      Concentrations of beta hydroxybutyrate were positively correlated with those of
      13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased
      at PP. These data demonstrate that prepartum adiposity predisposes cows to
      intense lipolysis post-partum and may exacerbate AT inflammation because of
      increased production of pro-inflammatory oxylipids including 5- and 15-HETE and
      13-HODE. These results support a role for certain linoleic and arachidonic acid
      derived oxylipids as positive and negative modulators of AT inflammation during
      periparturient lipolysis.

PMID- 29206844
TI  - Restoration of the prolyl-hydroxylase domain protein-3 oxygen-sensing mechanism
      is responsible for regulation of HIF2alpha expression and induction of
      sensitivity of myeloma cells to hypoxia-mediated apoptosis.
AB  - Multiple myeloma (MM) is an incurable disease of malignant plasma B-cells that
      infiltrate the bone marrow (BM), resulting in bone destruction, anemia, renal
      impairment and infections. Physiologically, the BM microenvironment is hypoxic
      and this promotes MM progression and contributes to resistance to chemotherapy.
      Since aberrant hypoxic responses may result in the selection of more aggressive
      tumor phenotypes, we hypothesized that targeting the hypoxia-inducible factor
      (HIF) pathways will be an effective anti-MM therapeutic strategy. We demonstrated
      that MM cells are resistant to hypoxia-mediated apoptosis in vivo and in vitro,
      and that constitutive expression of HIF2alpha contributed to this resistance.
      Since epigenetic silencing of the prolyl-hydroxylase-domain-3 (PHD3) enzyme
      responsible for the O2-dependent regulation of HIF2alpha is frequently observed
      in MM tumors, we asked if PHD3 plays a role in regulating sensitivity to hypoxia.
      We found that restoring PHD3 expression using a lentivirus vector or overcoming
      PHD3 epigenetic silencing using a demethyltransferase inhibitor, 5-Aza-2'
      deoxycytidine (5-Aza-dC), rescued O2-dependent regulation of HIF2alpha and
      restored sensitivity of MM cells to hypoxia-mediated apoptosis. This provides a
      rationale for targeting the PHD3-mediated regulation of the adaptive cellular
      hypoxic response in MM and suggests that targeting the O2-sensing pathway, alone
      or in combination with other anti-myeloma chemotherapeutics, may have clinical
      efficacy.

PMID- 29206845
TI  - Turbulence in protein folding: Vorticity, scaling and diffusion of probability
      flows.
AB  - Recently, when studying folding of a SH3 domain, we discovered that the flows of
      transitions between protein states can be surprisingly similar to turbulent fluid
      flows. This similarity was not restricted by a vortex pattern of the flow fields
      but extended to a spatial correlation of flow fluctuations, resulting, in
      particular, in the structure functions such as in the Kolmogorov theory of
      homogeneous and isotropic turbulence. Here, we undertake a detailed analysis of
      spatial distribution of folding flows and their similarity to turbulent fluid
      flows. Using molecular dynamics simulations, we study folding of another
      benchmark system-Trp-cage miniprotein, which has different content of secondary
      structure elements and mechanism of folding. Calculating the probability fluxes
      of transitions in a three-dimensional space of collective variables, we have
      found that similar to the SH3 domain, the structure functions of the second and
      third orders correspond to the Kolmogorov functions. The spatial distributions of
      the probability fluxes are self-similar with a fractal dimension, and the fractal
      index decreases toward the native state, indicating that the flow becomes more
      turbulent as the native state is approached. We also show that the process of
      folding can be viewed as Brownian diffusion in the space of probability fluxes.
      The diffusion coefficient plays a role of the key parameter that defines the
      structures functions, similar to the rate of dissipation of kinetic energy in
      hydrodynamic turbulence. The obtained results, first, show that the very complex
      dynamics of protein folding allows a simple characterization in terms of scaling
      and diffusion of probability fluxes, and, secondly, they suggest that the
      turbulence phenomena similar to hydrodynamic turbulence are not specific of
      folding of a particular protein but are common to protein folding.

PMID- 29206846
TI  - Bacterial community composition in the gut content of Lampetra japonica revealed
      by 16S rRNA gene pyrosequencing.
AB  - The composition of the bacterial communities in the hindgut contents of Lampetrs
      japonica was surveyed by Illumina MiSeq of the 16S rRNA gene. An average of 32385
      optimized reads was obtained from three samples. The rarefaction curve based on
      the operational taxonomic units tended to approach the asymptote. The rank
      abundance curve representing the species richness and evenness was calculated.
      The composition of microbe in six classification levels was also analyzed. Top 20
      members in genera level were displayed as the classification tree. The abundance
      of microorganisms in different individuals was displayed as the pie charts at the
      branch nodes in the classification tree. The differences of top 50 genera in
      abundance between individuals of lamprey are displayed as a heatmap. The pairwise
      comparison of bacterial taxa abundance revealed that there are no significant
      differences of gut microbiota between three individuals of lamprey at a given
      rarefied depth. Also, the gut microbiota derived from L. japonica displays little
      similarity with other aquatic organism of Vertebrata after UPGMA analysis. The
      metabolic function of the bacterial communities was predicted through KEGG
      analysis. This study represents the first analysis of the bacterial community
      composition in the gut content of L. japonica. The investigation of the gut
      microbiota associated with L. japonica will broaden our understanding of this
      unique organism.

PMID- 29206847
TI  - "Gaining or losing": The importance of the perspective in primary care health
      services valuation.
AB  - RATIONALE AND OBJECTIVES: Economic theory classifies an intervention as socially
      beneficial if the total Willingness to Pay (WTP) of those who gain exceeds the
      total Willingness to accept (WTA) of those who are harmed. This paper examines
      the differences in health system users' valuation of a health care service in
      primary care setting based on the WTP and WTA perspectives, discussing the impact
      of personal and service variables, including risk attitudes, on these
      disparities. METHOD: Six hundred and sixty two subjects who asked for care in
      health centres in the Region of Madrid (Spain) were interviewed, using the
      contingent valuation method to estimate WTP and WTA. Patient sociodemographic
      characteristics, health needs, satisfaction with the service and risk attitude
      and behaviour under risk (measured by self-reported scales and lottery games
      respectively) were collected. Generalised Linear Models were used to estimate the
      association between the explanatory variables and the WTA/WTP ratio. RESULTS: We
      obtained the WTA/WTP ratio for 570 subjects (mean 1.66 CI 95%: 1.53-1.79; median
      1, interquartile range 1-2). People with higher education or in high social
      groups expressed WTA values closest to WTP. The opposite occurred in patients
      with the greatest health needs or who were born abroad. Self-reported expression
      of risk aversion appeared also related to increases in the WTA/WTP ratio.
      Satisfaction with the service evaluated was the most influential factor in the
      WTA/WTP ratio. CONCLUSION: Health need, difficulty in obtaining substitutes and
      satisfaction with the service could serve for profiling people averse to loss for
      health care services in primary care setting. Self-reported expression of risk
      aversion could also be related to increases in the WTA/WTP ratio. This would mean
      that these characteristics should be taken into account both in the design and
      implementation of new healthcare interventions, as in the making decision for
      disinvestment.

PMID- 29206848
TI  - Caveolin-3 promotes glycometabolism, growth and proliferation in muscle cells.
AB  - OBJECTIVE: Caveolin-3 (CAV3) protein is known to be expressed specifically in
      various myocytes, but its physiological function remains unclear. CAV3, located
      at the cell membrane, may promote the sensitivity of the Akt signaling pathway,
      which is closely related to glucose metabolism and to cell growth and
      proliferation. METHODS: The CAV3 gene was stably transfected into C2C12 muscle
      cells, and the effects were evaluated by biochemical assays, WB and confocal
      microscopy for the observation of cellular glucose metabolism, growth and
      proliferation, and the effect of CAV3 on the Akt signaling pathway with no
      insulin stimulation. RESULTS: After C2C12 cells were transfected with the mouse
      CAV3 gene, which increased CAV3 expression, the abundance of the CAV3 and GLUT4
      proteins on the cell membrane increased, but the total GLUT4 protein content of
      the cell was unchanged. Glucose uptake was increased, and this did not affect the
      glycogen synthesis, but the cell surface area and cell proliferation increased.
      While there were significant increases in p-Akt and p-p70s6K, which is a
      downstream component of Akt signaling, the level of GSK3beta protein, another
      component of Akt signaling did not change. CONCLUSIONS: The muscle, CAV3 protein
      can activate Akt signaling, increase GLUT4 protein localization in the cell
      membrane, increase glucose uptake, and promote myocyte growth and proliferation.
      CAV3 protein has a physiological role in glycometabolism, growth and
      proliferation, independent of insulin stimulation.

PMID- 29206849
TI  - Cilostazol attenuates intimal hyperplasia in a mouse model of chronic kidney
      disease.
AB  - Intimal hyperplasia (IH) is a common cause of vasculopathy due to direct
      endothelial damage (such as post-coronary revascularization) or indirect injury
      (such as chronic kidney disease, or CKD). Although the attenuation of coronary
      revascularization-induced IH (direct-vascular-injury-induced IH) by cilostazol, a
      phosphodiesterase III inhibitor, has been demonstrated, our understanding of the
      effect on CKD-induced IH (indirect-vascular-injury-induced IH) is limited.
      Herein, we tested if cilostazol attenuated CKD-induced IH in a mouse model of
      ischemic-reperfusion injury with unilateral nephrectomy (Chr I/R), a normotensive
      non-proteinuria CKD model. Cilostazol (50 mg/kg/day) or placebo was orally
      administered once daily from 1-week post-nephrectomy. At 20 weeks, cilostazol
      significantly attenuated aortic IH as demonstrated by a 34% reduction in the
      total intima area with 50% and 47% decreases in the ratios of tunica intima
      area/tunica media area and tunica intima area/(tunica intima + tunica media
      area), respectively. The diameters of aorta and renal function were unchanged by
      cilostazol. Interestingly, cilostazol decreased miR-221, but enhanced miR-143 and
      miR-145 in either in vitro or aortic tissue, as well as attenuated several pro
      inflammatory mediators, including asymmetrical dimethylarginine, high-sensitivity
      C-reactive protein, vascular endothelial growth factor in aorta and serum pro
      inflammatory cytokines (IL-6 and TNF-alpha). We demonstrated a proof of concept
      of the effectiveness of cilostazol in attenuating IH in a Chr I/R mouse model, a
      CKD model with predominantly indirect-vascular-injury-induced IH. These
      considerations warrant further investigation to develop a new primary prevention
      strategy for CKD-related IH.

PMID- 29206850
TI  - The prognostic value of asymmetric dimethylarginine in patients with cardiac
      syndrome X.
AB  - BACKGROUND: The pathophysiology of cardiac syndrome X is multifactorial and
      endothelial dysfunction has been implicated as important contributing factor.
      Asymmetric dimethylarginine (ADMA), characterized as a circulating endogenous
      inhibitor of nitric oxide synthase, may have been implicated as an important
      contributing factor for the development of endothelial dysfunction. In this
      study, we aim to assess the predictive power of ADMA for long-term prognosis in
      patients with cardiac syndrome X. METHODS AND RESULTS: We enrolled 239
      consecutive patients with cardiac syndrome X diagnosed by coronary angiography.
      The mean age was 58.7+/-10.1 years. The patients were grouped into tertiles
      according to the plasma ADMA levels: <0.38 MUmol/l (tertile I), 0.38-0.44 MUmol/l
      (tertile II), and >0.44 MUmol/l (tertile III). All patients were followed up for
      a mean period of 6.5+/-1.5 years (median: 6.3 years, inter-quartile range: 5.7
      8.0 years). During the follow-up period, major adverse events (MAE) were observed
      in 15 patients (6.3%), including 13 deaths. The plasma ADMA levels in patients
      who developed MAE were significantly higher than those who did not (0.48+/-0.06
      MUmol/l vs. 0.42+/-0.08 MUmol/l, p = 0.005). In multivariate Cox regression
      analysis adjusted for age, eGFR and LVEF, ADMA tertile I and II were identify to
      be associated with a significantly lower risk of MAE compared to ADMA tertile III
      (p = 0.017). By considering the plasma ADMA level as a continuous variable, the
      plasma ADMA level remained a significant independent predictor for outcomes of
      MAE, and the relative risk of MACE increased by 50% when plasma ADMA level
      increased by 1 SD of value (p = 0.018). CONCLUSIONS: In patients with cardiac
      syndrome X, elevated plasma ADMA levels appeared to be an independent predictor
      of long-term adverse clinical outcomes.

PMID- 29206851
TI  - Role of viral coinfections in asthma development.
AB  - BACKGROUND: Viral respiratory infections, especially acute bronchiolitis, play a
      key role in the development of asthma in childhood. However, most studies have
      focused on respiratory syncytial virus or rhinovirus infections and none of them
      have compared the long-term evolution of single versus double or multiple viral
      infections. OBJECTIVE: Our aim was to compare the frequency of asthma development
      at 6-8 years in children with previous admission for bronchiolitis associated
      with single versus double or multiple viral infection. PATIENTS & METHODS: A
      cross-sectional study was performed in 244 children currently aged 6-8 years,
      previously admitted due to bronchiolitis between September 2008 and December
      2011. A structured clinical interview and the ISAAC questionnaire for asthma
      symptoms for 6-7-year-old children, were answered by parents by telephone.
      Specimens of nasopharyngeal aspirate for virological study (polymerase chain
      reaction) and clinical data were prospectively taken during admission for
      bronchiolitis. RESULTS: Median current age at follow-up was 7.3 years (IQR: 6.7
      8.1). The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7%
      in the single-infection group, p = 0.06. The number of wheezing-related
      admissions was twice as high in coinfections than in single infections, p =
      0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of
      single infections, p = 0.01, presented "wheezing in the last 12 months", data
      that strongly correlate with current prevalence of asthma. "Dry cough at night"
      was also reported more frequently in coinfections than in single infections, p =
      0.02. The strongest independent risk factors for asthma at 6-8 years of age were:
      age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317,
      p:0.005), allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001), and viral
      coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01). CONCLUSIONS:
      Asthma at 6-8 years is more frequent and severe in those children previously
      hospitalized with viral coinfection-bronchiolitis compared with those with single
      infection. Allergic rhinitis and older age at admission seem also to be strong
      independent risk factors for asthma development in children previously
      hospitalised because of bronchiolitis.

PMID- 29206852
TI  - Psychological, pharmacological, and combined smoking cessation interventions for
      smokers with current depression: A systematic review and meta-analysis.
AB  - We conducted a systematic literature review and meta-analysis (ID:
      CRD42016051017) of smoking cessation interventions for patients with current
      depression. We examined the effectiveness of smoking cessation treatments in
      improving abstinence rates and depressive symptoms. The following electronic
      databases were used for potentially eligible studies: PUBMED, PSYCINFO, DIALNET
      and WEB OF KNOWLEDGE. The search terms used were: smoking cessation, depressive
      disorder, depression, mood, depressive, depressed, smoking, smokers, nicotine,
      nicotine dependence, and tobacco cigarette smoking. The methodological quality of
      included studies was assessed using the Effective Public Health Practice Project
      Quality assessment tool (EPHPP). Of the 6,584 studies identified, 20 were
      eligible and included in the review. Trial designs of studies were 16 randomized
      controlled trials and 4 secondary studies. Studies included three types of
      intervention: psychological (6/30%), pharmacological (6/30%) or combined (8/40%).
      Four trials comprised special populations of smokers. Four studies received a
      strong methodological quality, 7 were scored as moderate and 9 studies received a
      weak methodological rating. Analyses of effectiveness showed that smoking
      cessation interventions appear to increase short-term and long-term smoking
      abstinence in individuals with current depression. Subgroup analyses revealed
      stronger effects among studies that provided pharmacological treatments than in
      studies using psychological treatments. However, the evidence is weak due to the
      small number of studies. Smoking abstinence appears to be associated with an
      improvement in depressive symptoms. Heterogeneity in protocols in similar types
      of treatment also prevent firm conclusions being drawn on the effectiveness of
      any particular treatment model to optimally manage abstinence among depressed
      smokers. Further research is required to strengthen the evidence base.

PMID- 29206853
TI  - Proportion and factors associated with recent HIV infection in a cohort of
      patients seen for care in Italy over 1996-2014: Data from the ICONA Foundation
      Study cohort.
AB  - In Italy the prevalence of recent HIV infection (RHI) isn't currently monitored.
      Early diagnosis is crucial to allow introduction of antiretroviral therapy (cART)
      in the recent phase of infection. We aimed to estimate the proportion and the
      determinants of RHI among patients enrolled in the ICONA cohort; we explored
      differences in the median time from HIV diagnosis to cART initiation and in the
      viro-immunological response between RHI and Less Recent HIV infections (NRHI). We
      included antiretroviral-naive HIV-positive patients enrolled in the cohort with
      documented dates of HIV-negative and positive antibodies tests, grouped in RHI
      (estimated date of seroconversion within 12 months of enrolment) and NRHI.
      Proportion of RHI and the trend of this proportion by calendar period (1996-2014)
      were investigated (Chi-square test). Logistic regression analysis was employed to
      identify factors associated with RHI. The time from seroconversion to cART
      initiation was compared in RHI and NRHI overall and after stratification by
      calendar period (survival analysis). We finally explored the time from starting
      cART to HIV-RNA <50 copies/mL and to CD4+ gain >=200 cells/mmc by Cox regression.
      HIV seroconversion could be estimated for 2608/12,616 patients: 981/2608 (37.6%)
      were RHI. Proportion of RHI increased in recent calendar periods and was
      associated with younger age, baseline higher HIV-RNA and CD4+ count. There wasn't
      difference in the 2-year estimates of cART start between RHI and NRHI, regardless
      of calendar period. Rates and hazards of virological response were similar in RHI
      versus NRHI. RHI showed a 1.5-fold higher probability of CD4+ gain, also
      following adjustment for calendar period and cART regimen, and for age, HCV and
      smoking; the difference in probability was however attenuated after further
      controlling for baseline HIV-RNA and CD4+ T-cells. The increased proportion of
      RHI over time suggests that in recent years in Italy HIV infections are more
      likely to be detected earlier than before. The similar rates of cART introduction
      and viro-immunological response in RHI and NRHI probably reflect the efficacy of
      the modern cART regimens. An improvement of the prevention services is warranted
      to allow an early cART access, also in the perspective of therapy as prevention.

PMID- 29206854
TI  - Zingerone alleviates the delayed ventricular repolarization and AV conduction in
      diabetes: Effect on cardiac fibrosis and inflammation.
AB  - BACKGROUND: The study aims to analyse the action of zingerone in diabetes-related
      cardiac arrhythmias. METHODS: Diabetes was induced by streptozocin while
      treatment groups received 20 mg/kg zingerone daily. Following extra seven weeks,
      electrocardiography, extraction of blood, urine and heart for biochemical
      analysis, histopathology and immunofluorescence were undertaken. RESULTS: The
      suppression of QT and QTc prolongation in diabetic rats was indicative of
      prolonged cardiac repolarisation that was greatly reduced by zingerone treatment.
      In addition, the reduction in PR interval attested that zingerone improved AV
      delay in diabetic rats. The fibrogenic transforming growth factor beta1
      upregulation in diabetic hearts was suppressed by zingerone. The marked glycogen
      deposition and muscle degeneration seen in diabetic heart sections were also
      alleviated by zingerone. Furthermore, zingerone prevented the decrease in of the
      serum anti-inflammatory cytokine adiponectin in diabetics. The heightened levels
      of oxidative stress markers 8-isoprostane and uric acid in diabetic rats were
      suppressed. In the diabetic heart, the reduced catalase activity was improved and
      the excessive expression of angiotensin receptor 1 was inhibited by zingerone.
      CONCLUSION: Cardiac delayed repolarisation and AV conduction in rats with
      diabetes were halted by zingerone. It appears that inhibition of cardiac fibrosis
      and associated inflammation-oxidative stress signalling underpins the zingerone
      effect.

PMID- 29206855
TI  - Linking disease epidemiology and livestock productivity: The case of bovine
      respiratory disease in France.
AB  - Concerns are growing over the impact of livestock farming on environment and
      public health. The livestock industry is faced with the double constraint of
      limiting its use of natural resources and antimicrobials while ensuring its
      economic sustainability. In this context, reliable methods are needed to evaluate
      the effect of the prevention of endemic animal diseases on the productivity of
      livestock production systems. In this study, an epidemiological and productivity
      model was used to link changes in Bovine Respiratory Disease (BRD) incidence with
      the productivity of the beef and dairy cattle sectors in France. Cattle
      production parameters significantly affected by BRD were selected through
      literature review. Previous field study results and national cattle performance
      estimates were used to infer growth performances, mortality rates and carcass
      quality in the cattle affected and not affected by BRD. A steady-state
      deterministic herd production model was used to predict the productivity of the
      dairy and beef sector and their defined compartments (breeding-fattening, feedlot
      young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or
      100%. Results suggested that BRD should be controlled at a priority in beef
      breeding farms as eradication of BRD in beef calves would increase the whole beef
      sector's productivity by 4.7-5.5% while eradication in other production stages
      would result in lower productivity gain in their respective sectors. However, the
      analysis performed at compartment level showed that, in both the beef and dairy
      sector, young bull and veal feedlot enterprises derive more economic benefits
      from BRD eradication for their own compartment (increase in productivity of 8.7
      12.8% for beef young bulls) than the breeding farms (increase in productivity of
      5.1-6% for beef calves), which may limit the investments in BRD control.

PMID- 29206856
TI  - A novel post-processing scheme for two-dimensional electrical impedance
      tomography based on artificial neural networks.
AB  - OBJECTIVE: Electrical Impedance Tomography (EIT) is a powerful non-invasive
      technique for imaging applications. The goal is to estimate the electrical
      properties of living tissues by measuring the potential at the boundary of the
      domain. Being safe with respect to patient health, non-invasive, and having no
      known hazards, EIT is an attractive and promising technology. However, it suffers
      from a particular technical difficulty, which consists of solving a nonlinear
      inverse problem in real time. Several nonlinear approaches have been proposed as
      a replacement for the linear solver, but in practice very few are capable of
      stable, high-quality, and real-time EIT imaging because of their very low
      robustness to errors and inaccurate modeling, or because they require
      considerable computational effort. METHODS: In this paper, a post-processing
      technique based on an artificial neural network (ANN) is proposed to obtain a
      nonlinear solution to the inverse problem, starting from a linear solution. While
      common reconstruction methods based on ANNs estimate the solution directly from
      the measured data, the method proposed here enhances the solution obtained from a
      linear solver. CONCLUSION: Applying a linear reconstruction algorithm before
      applying an ANN reduces the effects of noise and modeling errors. Hence, this
      approach significantly reduces the error associated with solving 2D inverse
      problems using machine-learning-based algorithms. SIGNIFICANCE: This work
      presents radical enhancements in the stability of nonlinear methods for
      biomedical EIT applications.

PMID- 29206857
TI  - Z-disc protein CHAPb induces cardiomyopathy and contractile dysfunction in the
      postnatal heart.
AB  - AIMS: The Z-disc is a crucial structure of the sarcomere and is implicated in
      mechanosensation/transduction. Dysregulation of Z-disc proteins often result in
      cardiomyopathy. We have previously shown that the Z-disc protein Cytoskeletal
      Heart-enriched Actin-associated Protein (CHAP) is essential for cardiac and
      skeletal muscle development. Furthermore, the CHAP gene has been associated with
      atrial fibrillation in humans. Here, we studied the misregulated expression of
      CHAP isoforms in heart disease. METHODS AND RESULTS: Mice that underwent
      transverse aortic constriction and calcineurin transgenic (Tg) mice, both models
      of experimental heart failure, displayed a significant increase in cardiac
      expression of fetal isoform CHAPb. To investigate whether increased expression of
      CHAPb postnatally is sufficient to induce cardiomyopathy, we generated CHAPb Tg
      mice under the control of the cardiac-specific alphaMHC promoter. CHAPb Tg mice
      displayed cardiac hypertrophy, interstitial fibrosis and enlargement of the left
      atrium at three months, which was more pronounced at the age of six months.
      Hypertrophy and fibrosis were confirmed by evidence of activation of the
      hypertrophic gene program (Nppa, Nppb, Myh7) and increased collagen expression,
      respectively. Connexin40 and 43 were downregulated in the left atrium, which was
      associated with delayed atrioventricular conduction. Tg hearts displayed both
      systolic and diastolic dysfunction partly caused by impaired sarcomere function
      evident from a reduced force generating capacity of single cardiomyocytes. This
      co-incided with activation of the actin signalling pathway leading to the
      formation of stress fibers. CONCLUSION: This study demonstrated that the fetal
      isoform CHAPb initiates progression towards cardiac hypertrophy, which is
      accompanied by delayed atrioventricular conduction and diastolic dysfunction.
      Moreover, CHAP may be a novel therapeutic target or candidate gene for screening
      in cardiomyopathies and atrial fibrillation.

PMID- 29206858
TI  - Extreme metal adapted, knockout and knockdown strains reveal a coordinated gene
      expression among different Tetrahymena thermophila metallothionein isoforms.
AB  - Metallothioneins (MT) constitute a superfamily of small cytosolic proteins that
      are able to bind metal cations through numerous cysteine (Cys) residues. Like
      other organisms the ciliate Tetrahymena thermophila presents several MT isoforms,
      which have been classified into two subfamilies (Cd- and Cu-metallothioneins).
      The main aim of this study was to examine the specific functions and
      transcriptional regulation of the five MT isoforms present in T. thermophila, by
      using several strains of this ciliate. After a laboratory evolution experiment
      over more than two years, three different T. thermophila strains adapted to
      extreme metal stress (Cd2+, Cu2+ or Pb2+) were obtained. In addition, three
      knockout and/or knockdown strains for different metallothionein (MT) genes were
      generated. These strains were then analyzed for expression of the individual MT
      isoforms. Our results provide a strong basis for assigning differential roles to
      the set of MT isoforms. MTT1 appears to have a key role in adaptation to Cd. In
      contrast, MTT2/4 are crucial for Cu-adaptation and MTT5 appears to be important
      for Pb-adaptation and might be considered as an "alarm" MT gene for responding to
      metal stress. Moreover, results indicate that likely a coordinated
      transcriptional regulation exists between the MT genes, particularly among MTT1,
      MTT5 and MTT2/4. MTT5 appears to be an essential gene, a first such report in any
      organism of an essential MT gene.

PMID- 29206859
TI  - Proteus mirabilis inhibits cancer growth and pulmonary metastasis in a mouse
      breast cancer model.
AB  - A variety of bacteria have been used as agents and vectors for antineoplastic
      therapy. A series of mechanisms, including native bacterial toxicity,
      sensitization of the immune system and competition for nutrients, may contribute
      to antitumor effects. However, the antitumor effects of Proteus species have been
      minimally studied, and it is not clear if bacteria can alter tumor hypoxia as a
      component of their antineoplastic effect. In the present study, Proteus mirabilis
      bacteria were evaluated for the ability to proliferate and accumulate in murine
      tumors after intravenous injection. To further investigate the efficacy and
      safety of bacterial injection, mice bearing 4T1 tumors were treated with an
      intravenous dose of 5*107 CFU Proteus mirabilis bacteria via the tail vein weekly
      for three treatments. Histopathology, immunohistochemistry (IHC) and western
      analysis were then performed on excised tumors. The results suggested Proteus
      mirabilis localized preferentially to tumor tissues and remarkably suppressed the
      growth of primary breast cancer and pulmonary metastasis in murine 4T1 models.
      Results showed that the expression of NKp46 and CD11c was significantly increased
      after bacteria treatment. Furthermore, tumor expression of carbonic anhydrase IX
      (CA IX) and hypoxia inducible factor-1a (HIF-1a), surrogates for hypoxia, was
      significantly lower in the treated group than the control group mice as assessed
      by IHC and western analysis. These findings demonstrated that Proteus mirabilis
      may a promising bacterial strain for used against primary tumor growth and
      pulmonary metastasis, and the immune system and reduction of tumor hypoxia may
      contribute to the antineoplastic and antimetastatic effects observed.

PMID- 29206860
TI  - The acute glucose lowering effect of specific GPR120 activation in mice is mainly
      driven by glucagon-like peptide 1.
AB  - The mechanism behind the glucose lowering effect occurring after specific
      activation of GPR120 is not completely understood. In this study, a potent and
      selective GPR120 agonist was developed and its pharmacological properties were
      compared with the previously described GPR120 agonist Metabolex-36. Effects of
      both compounds on signaling pathways and GLP-1 secretion were investigated in
      vitro. The acute glucose lowering effect was studied in lean wild-type and GPR120
      null mice following oral or intravenous glucose tolerance tests. In vitro, in
      GPR120 overexpressing cells, both agonists signaled through Galphaq, Galphas and
      the beta-arrestin pathway. However, in mouse islets the signaling pathway was
      different since the agonists reduced cAMP production. The GPR120 agonists
      stimulated GLP-1 secretion both in vitro in STC-1 cells and in vivo following
      oral administration. In vivo GPR120 activation induced significant glucose
      lowering and increased insulin secretion after intravenous glucose administration
      in lean mice, while the agonists had no effect in GPR120 null mice. Exendin 9-39,
      a GLP-1 receptor antagonist, abolished the GPR120 induced effects on glucose and
      insulin following an intravenous glucose challenge. In conclusion, GLP-1
      secretion is an important mechanism behind the acute glucose lowering effect
      following specific GPR120 activation.

PMID- 29206861
TI  - Preparative two-step purification of recombinant H1.0 linker histone and its
      domains.
AB  - H1 linker histones are small basic proteins that have a key role in the formation
      and maintenance of higher-order chromatin structures. Additionally, many examples
      have shown that linker histones play an important role in gene regulation,
      modulated by their various subtypes and posttranslational modifications.
      Obtaining high amounts of very pure linker histones, especially for efficient
      antibody production, remains a demanding and challenging procedure. Here we
      present an easy and fast method to purify human linker histone H1.0 overexpressed
      in Escherichia coli, as well as its domains: N-terminal/globular domain and C
      terminal intrinsically disordered domain. This purification protocol relies on a
      simple affinity chromatography step followed by cation exchange due to the highly
      basic properties of histone proteins. Therefore, this protocol can also be
      applied to other linker histones. Highly pure proteins in amounts sufficient for
      most biochemical experiments can be obtained. The functional quality of purified
      H1.0 histone and its domains has been confirmed by pull-down, gel-mobility shift
      assays and the nuclear import assay.

PMID- 29206862
TI  - Recombinant human IL-26 facilitates the innate immune response to endotoxin in
      the bronchoalveolar space of mice in vivo.
AB  - Interleukin (IL)-26 is released in response to bacterial endotoxin (LPS) in the
      bronchoalveolar space of humans in vivo and it may potentiate neutrophil
      chemotaxis by enhanced IL-26 receptor stimulation. However, the effects of
      extracellular IL-26 protein on the innate immune response in the lungs in vivo
      remain unknown. Here, we characterized these effects of IL-26 on a wide range of
      aspects of the innate immune response to LPS in different compartments of the
      lungs in vivo over time. We administrated recombinant human (rh) IL-26 protein in
      the bronchoalveolar space using intranasal instillation in a mouse in vivo model,
      with and without prior instillation of LPS. We verified gene expression of the IL
      26 receptor complex in mouse lungs and observed that, after instillation of LPS,
      rhIL-26 increases the phosphorylation of STAT3, a signaling molecule of the IL-26
      receptor complex. We also observed that rhIL-26 exerted additional stimulatory
      and inhibitory actions that are compartment- and time-dependent, resulting in
      alterations of cytokines, proteinases, tissue inflammation and the accumulation
      of innate effector cells. Without the prior instillation of LPS, rhIL-26 exerted
      time-dependent effects on total gelatinase activity but few other effects. Most
      important, after instillation of LPS, rhIL-26 cleared inflammatory cells from
      local tissue and increased the accumulation of innate effector cells in the
      bronchoalveolar space. Tentatively, rhIL-26 may facilitate the innate immune
      response towards the bronchoalveolar space in vivo and represents a potential
      target for therapy in lung disorders involving the innate immune response.

PMID- 29206863
TI  - Blood collection in cell-stabilizing tubes does not impact germline DNA quality
      for pediatric patients.
AB  - OBJECTIVES: Liquid biopsy technologies allow non-invasive tumor profiling for
      patients with solid tumor malignancies by sequencing circulating tumor DNA. These
      studies may be useful in risk-stratification, monitoring for relapse, and
      understanding tumor evolution. The quality of DNA obtained for these studies is
      improved when blood samples are collected in tubes that stabilizing white blood
      cells (WBC). However, ongoing germline research in pediatric oncology generally
      requires obtaining blood samples in EDTA tubes, which do not contain a WBC
      stabilizing preservative. In this study, we explored whether blood samples
      collected in WBC-stabilizing tubes could be used for both liquid biopsy and
      germline studies simultaneously, minimizing blood collection volumes for
      pediatric patients. METHODS: Blood was simultaneously collected from three
      patients in both EDTA and Streck Cell-Free DNA BCT(r) tubes. Germline DNA was
      extracted from all blood samples and subjected to whole-exome sequencing and
      microarray profiling. RESULTS: Quality control metrics of DNA quality, sequencing
      library preperation and whole-exome sequencing alignment were virtually identical
      regardless of the sample collection method. There was no discernable difference
      in patterns of variant calling for paired samples by either whole-exome
      sequencing or microarray analysis. CONCLUSION: Our study demonstrates that high
      quality genomic studies may be performed from germline DNA obtained in Streck
      tubes. Therefore, these tubes may be used to simultaneously obtain samples for
      both liquid biopsy and germline studies in pediatric patients when the volume of
      blood available for research studies may be limited.

PMID- 29206864
TI  - High visual acuity revealed in dogs.
AB  - Humans have selectively bred and used dogs over a period of thousands of years,
      and more recently the dog has become an important model animal for studies in
      ethology, cognition and genetics. These broad interests warrant careful
      descriptions of the senses of dogs. Still there is little known about dog vision,
      especially what dogs can discriminate in different light conditions. We trained
      and tested whippets, pugs, and a Shetland sheepdog in a two-choice discrimination
      set-up and show that dogs can discriminate patterns with spatial frequencies
      between 5.5 and 19.5 cycle per degree (cpd) in the bright light condition (43 cd
      m-2). This is a higher spatial resolution than has been previously reported
      although the individual variation in our tests was large. Humans tested in the
      same set-up reached acuities corresponding to earlier studies, ranging between
      32.1 and 44.2 cpd. In the dim light condition (0.0087 cd m-2) the acuity of dogs
      ranged between 1.8 and 3.5 cpd while in humans, between 5.9 and 9.9 cpd. Thus,
      humans make visual discrimination of objects from roughly a threefold distance
      compared to dogs in both bright and dim light.

PMID- 29206866
TI  - An adaptive map-matching algorithm based on hierarchical fuzzy system from
      vehicular GPS data.
AB  - An improved hierarchical fuzzy inference method based on C-measure map-matching
      algorithm is proposed in this paper, in which the C-measure represents the
      certainty or probability of the vehicle traveling on the actual road. A strategy
      is firstly introduced to use historical positioning information to employ curve
      curve matching between vehicle trajectories and shapes of candidate roads. It
      improves matching performance by overcoming the disadvantage of traditional map
      matching algorithm only considering current information. An average historical
      distance is used to measure similarity between vehicle trajectories and road
      shape. The input of system includes three variables: distance between position
      point and candidate roads, angle between driving heading and road direction, and
      average distance. As the number of fuzzy rules will increase exponentially when
      adding average distance as a variable, a hierarchical fuzzy inference system is
      then applied to reduce fuzzy rules and improve the calculation efficiency.
      Additionally, a learning process is updated to support the algorithm. Finally, a
      case study contains four different routes in Beijing city is used to validate the
      effectiveness and superiority of the proposed method.

PMID- 29206865
TI  - Regulation of potassium dependent ATPase (kdp) operon of Deinococcus radiodurans.
AB  - The genome of D. radiodurans harbors genes for structural and regulatory proteins
      of Kdp ATPase, in an operon pattern, on Mega plasmid 1. Organization of its two
      component regulatory genes is unique. Here we demonstrate that both, the
      structural as well as regulatory components of the kdp operon of D. radiodurans
      are expressed quickly as the cells experience potassium limitation but are not
      expressed upon increase in osmolarity. The cognate DNA binding response regulator
      (RR) effects the expression of kdp operon during potassium deficiency through
      specific interaction with the kdp promoter. Deletion of the gene encoding RR
      protein renders the mutant D. radiodurans (DeltaRR) unable to express kdp operon
      under potassium limitation. The DeltaRR D. radiodurans displays no growth defect
      when grown on rich media or when exposed to oxidative or heat stress but shows
      reduced growth following gamma irradiation. The study elucidates the functional
      and regulatory aspects of the novel kdp operon of this extremophile, for the
      first time.

PMID- 29206868
TI  - A model for foreign exchange markets based on glassy Brownian systems.
AB  - In this work we extend a well-known model from arrested physical systems, and
      employ it in order to efficiently depict different currency pairs of foreign
      exchange market price fluctuation distributions. We consider the exchange rate
      price in the time range between 2010 and 2016 at yearly time intervals and
      resolved at one minute frequency. We then fit the experimental datasets with this
      model, and find significant qualitative symmetry between price fluctuation
      distributions from the currency market, and the ones belonging to colloidal
      particles position in arrested states. The main contribution of this paper is a
      well-known physical model that does not necessarily assume the independent and
      identically distributed (i.i.d.) restrictive condition.

PMID- 29206867
TI  - GNB3 overexpression causes obesity and metabolic syndrome.
AB  - The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk;
      however, the molecular mechanism of GNB3-related disease is unknown. GNB3
      duplication is responsible for a syndromic form of childhood obesity, and an
      activating DNA sequence variant (C825T) in GNB3 is also associated with obesity.
      To test the hypothesis that GNB3 overexpression causes obesity, we created
      bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of
      the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased
      adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have
      elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose
      intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides,
      cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based
      on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or
      depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity
      levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute
      thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose
      tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to
      impaired cellular thermogenesis. Taken together, our study provides the first
      functional link between GNB3 and obesity, and presents insight into novel
      pathways that could be applied to combat obesity and type 2 diabetes.

PMID- 29206869
TI  - Measurements of 6-thioguanine nucleotide levels with TPMT and NUDT15 genotyping
      in patients with Crohn's disease.
AB  - The association between the 6-thioguanine nucleotide (6-TGN) level and clinical
      remission in Crohn's disease (CD) remains controversial. Thiopurine-induced
      leukopenia is a life-threatening complication of CD in Asians that was recently
      shown to strongly correlate with NUDT15 genetic variants. This study aimed to
      determine the relationship between thiopurine metabolite levels and therapeutic
      response, and to investigate the association of NUDT15, TPMT, and thiopurine
      metabolites with leukopenia in patients with CD. We enrolled 165 adult patients
      with CD undergoing thiopurine treatment. Clinical evaluation and laboratory
      examinations were carried out every 2-3 months. We measured thiopurine
      metabolites levels and genotyped NUDT15 and TPMT. During the median 12-month
      observational period, 95 (67.9%) patients exhibited clinical response and 45
      (32.1%) did not respond to the treatment. The median 6-TGN level was
      significantly higher in responders than in non-responders (P < 0.001). The odds
      ratio of patients with a 6-TGN level >=230 pmol/8 * 108 red blood cells for
      showing a clinical response was 4.63 (95% CI 1.62-11.9). NUDT15 variant types
      were strongly associated with developing leukopenia. Patients with NUDT15
      homozygous variant genotype developed severe early leukopenia with an average
      reduction of 88.2% (range, 84-94%) from the baseline white blood cell count at 4
      weeks. Our findings support the role of therapeutic drug monitoring in thiopurine
      maintenance treatment to optimize thiopurine therapy, especially, for non
      responding CD patients. Thiopurine treatment should not be recommended to
      patients with NUDT15 homozygous variant genotype due to severe early leukopenia.

PMID- 29206870
TI  - Loss of polarity alters proliferation and differentiation in low-grade
      endometrial cancers by disrupting Notch signaling.
AB  - Cell adhesion and apicobasal polarity together maintain epithelial tissue
      organization and homeostasis. Loss of adhesion has been described as a
      prerequisite for the epithelial to mesenchymal transition. However, what role
      misregulation of apicobasal polarity promotes tumor initiation and/or early
      progression remains unclear. We find that human low-grade endometrial cancers are
      associated with disrupted localization of the apical polarity protein Par3 and
      Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by
      decreased Notch signaling, and altered Notch receptor localization. Depletion of
      Par3 or Ezrin, in a cell-based model, results in loss of epithelial architecture,
      differentiation, increased proliferation, migration and decreased Notch
      signaling. Re-expression of Par3 in endometrial cancer cell lines with disrupted
      Par3 protein levels blocks proliferation and reduces migration in a Notch
      dependent manner. These data uncover a function for apicobasal polarity
      independent of cell adhesion in regulating Notch-mediated differentiation signals
      in endometrial epithelial cells.

PMID- 29206871
TI  - Clopidogrel in a combined therapy with anticancer drugs-effect on tumor growth,
      metastasis, and treatment toxicity: Studies in animal models.
AB  - Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely
      prescribed for patients with cardiovascular diseases. In addition to antiplatelet
      activity, antiplatelet agents possess anticancer and antimetastatic properties.
      Contrary to this, results of some studies have suggested that the use of
      clopidogrel and other thienopyridines accelerates the progression of breast,
      colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate
      the efficacy of clopidogrel and various anticancer agents as a combined treatment
      using mouse models of breast, colorectal, and prostate cancer. Metastatic
      dissemination, selected parameters of platelet morphology and biochemistry, as
      well as angiogenesis were assessed. In addition, body weight, blood morphology,
      and biochemistry were evaluated to test toxicity of the studied compounds.
      According to the results, clopidogrel increased antitumor and/or antimetastatic
      activity of chemotherapeutics such as 5-fluorouracil, cyclophosphamide, and
      mitoxantrone, whereas it decreased the anticancer activity of doxorubicin,
      cisplatin, and tamoxifen. The mechanisms of such divergent activities may be
      based on the modulation of tumor vasculature via factors, such as transforming
      growth factor beta1 released from platelets. Moreover, clopidogrel increased the
      toxicity of docetaxel and protected against mitoxantrone-induced toxicity, which
      may be due to the modulation of hepatic enzymes and protection of the
      vasculature, respectively. These results demonstrate that antiplatelet agents can
      be useful but also dangerous in anticancer treatment and therefore use of
      thienopyridines in patients undergoing chemotherapy should be carefully
      evaluated.

PMID- 29206873
TI  - Correction: Repurposed Transcriptomic Data Reveal Small Viral RNA Produced by
      Influenza Virus during Infection in Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0165729.].

PMID- 29206872
TI  - Socioeconomic disparities and sexual dimorphism in neurotoxic effects of ambient
      fine particles on youth IQ: A longitudinal analysis.
AB  - Mounting evidence indicates that early-life exposure to particulate air
      pollutants pose threats to children's cognitive development, but studies about
      the neurotoxic effects associated with exposures during adolescence remain
      unclear. We examined whether exposure to ambient fine particles (PM2.5) at
      residential locations affects intelligence quotient (IQ) during pre-/early-
      adolescence (ages 9-11) and emerging adulthood (ages 18-20) in a demographically
      diverse population (N = 1,360) residing in Southern California. Increased ambient
      PM2.5 levels were associated with decreased IQ scores. This association was more
      evident for Performance IQ (PIQ), but less for Verbal IQ, assessed by the
      Wechsler Abbreviated Scale of Intelligence. For each inter-quartile (7.73 MUg/m3)
      increase in one-year PM2.5 preceding each assessment, the average PIQ score
      decreased by 3.08 points (95% confidence interval = [-6.04, -0.12]) accounting
      for within-family/within-individual correlations, demographic characteristics,
      family socioeconomic status (SES), parents' cognitive abilities, neighborhood
      characteristics, and other spatial confounders. The adverse effect was 150%
      greater in low SES families and 89% stronger in males, compared to their
      counterparts. Better understanding of the social disparities and sexual
      dimorphism in the adverse PM2.5-IQ effects may help elucidate the underlying
      mechanisms and shed light on prevention strategies.

PMID- 29206874
TI  - Correction: Human babesiosis: Indication of a molecular mimicry between
      thrombospondin domains from a novel Babesia microti BmP53 protein and host
      platelets molecules.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185372.].

PMID- 29206875
TI  - Correction: Effects of insulin like growth factors on early embryonic chick limb
      myogenesis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185775.].

PMID- 29206877
TI  - Correction: Quality of life measures predict cardiovascular health and physical
      performance in chronic renal failure patients.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183926.].

PMID- 29206876
TI  - DNA barcoding, ecology and geography of the cryptic species of Aneura pinguis and
      their relationships with Aneura maxima and Aneura mirabilis (Metzgeriales,
      Marchantiophyta).
AB  - Aneura pinguis is a thalloid liverwort species with broad geographical
      distribution. It is composed of cryptic species, however, the number of cryptic
      species within A. pinguis is not known. Five cpDNA regions (matK, rbcL, rpoC1,
      trnH-psbA and trnL-trnF) and the entire nuclear ITS region were studied in 130
      samples of A. pinguis from different geographical regions. The relationships
      between the cryptic species of A. pinguis, A. maxima and A. mirabilis were
      analyzed. All of the examined samples were clustered into 10 clades corresponding
      to 10 cryptic species of A. pinguis (marked A to J). Aneura mirabilis and A.
      maxima were nested among different cryptic species of A. pinguis, which indicates
      that A. pinguis is a paraphyletic taxon. Subgroups were found in cryptic species
      A, B, C and E. As single barcodes, all tested DNA regions had 100% discriminant
      power and fulfilled DNA barcode criteria for species identification; however, the
      only combination detected in all subgroups was trnL-trnF with trnH-psbA or ITS2.
      The distances between cryptic species were 11- to 35-fold higher than
      intraspecific distances. In all analyzed DNA regions, the distances between most
      pairs of cryptic A. pinguis species were higher than between A. maxima and A.
      mirabilis. All cryptic species of A. pinguis clearly differed in their habitat
      preferences, which suggests that habitat adaptation could be the main driving
      force behind cryptic speciation within this taxon.

PMID- 29206878
TI  - Predictors of mercury, lead, cadmium and antimony status in Norwegian never
      pregnant women of fertile age.
AB  - BACKGROUND: The toxic trace elements mercury (Hg), lead (Pb), cadmium (Cd) and
      antimony (Sb) are transferred over the placenta to the fetus and secreted into
      the breastmilk. All four elements bioaccumulate in the body and as maternal age
      at delivery is increasing in industrialized countries, the burden of toxic trace
      elements in never-pregnant women of fertile age is of concern. METHODS: Healthy,
      never-pregnant women aged 18 to 40 years (n = 158) were recruited between June
      2012 and March 2015 in Bergen, Norway. Clinical data were collected and non
      fasting venous blood samples were analyzed for whole blood Hg, Pb and Cd and
      serum Sb by ICP-MS and related to diet and life style factors. RESULTS: In a
      multiple linear regression model, increasing age was associated with higher
      levels of Hg and Sb, but diet and life style factors were more important
      predictors. Median whole blood Hg was increased by a factor of 70 in women who
      had fish for dinner >=1/week, compared to women who rarely or never ate fish
      (p<0.001). Alcohol intake was the strongest predictor for whole blood Pb, while
      use of tobacco was the strongest predictor for whole blood Cd. Being a vegetarian
      was associated with lower levels of both Hg and Sb. CONCLUSIONS: As toxic trace
      elements tend to bioaccumulate in the body, increasing maternal age at delivery
      may represent a threat to the next generation. In a group of healthy Norwegian
      never-pregnant women, age contributed to Hg and Sb levels, but diet and life
      style factors were stronger determinants of whole blood Hg, Pb, Cd and serum Sb
      levels. Continuous public actions are needed to reduce modifiable and preventable
      sources of potentially deleterious toxins to minimize the exposure in children
      and fertile women.

PMID- 29206879
TI  - Climate change influences on the potential geographic distribution of the disease
      vector tick Ixodes ricinus.
AB  - BACKGROUND: Ixodes ricinus is a species of hard tick that transmits several
      important diseases in Europe and North Africa, including Lyme borreliosis and
      tick-borne encephalitis. Climate change is affecting the geographic distributions
      and abundances of arthropod vectors, which in turn influence the geographic
      distribution and epidemiology of associated vector-borne diseases. To date, few
      studies have investigated effects of climate change on the spatial distribution
      of I. ricinus at continental extents. Here, we assessed the potential
      distribution of I. ricinus under current and future climate conditions to
      understand how climate change will influence the geographic distribution of this
      important tick vector in coming decades. METHOD: We used ecological niche
      modeling to estimate the geographic distribution of I. ricinus with respect to
      current climate, and then assessed its future potential distribution under
      different climate change scenarios. This approach integrates occurrence records
      of I. ricinus with six relevant environmental variables over a continental extent
      that includes Europe, North Africa, and the Middle East. Future projections were
      based on climate data from 17 general circulation models (GCMs) under 2
      representative concentration pathway emissions scenarios (RCPs), for the years
      2050 and 2070. RESULT: The present and future potential distributions of I.
      ricinus showed broad overlap across most of western and central Europe, and in
      more narrow zones in eastern and northern Europe, and North Africa. Potential
      expansions were observed in northern and eastern Europe. These results indicate
      that I. ricinus populations could emerge in areas in which they are currently
      lacking, posing increased risks to human health in those areas. However, the
      future of I. ricinus ticks in some important regions such the Mediterranean was
      unclear owing to high uncertainty in model predictions.

PMID- 29206880
TI  - Improved multi-objective clustering algorithm using particle swarm optimization.
AB  - Multi-objective clustering has received widespread attention recently, as it can
      obtain more accurate and reasonable solution. In this paper, an improved multi
      objective clustering framework using particle swarm optimization (IMCPSO) is
      proposed. Firstly, a novel particle representation for clustering problem is
      designed to help PSO search clustering solutions in continuous space. Secondly,
      the distribution of Pareto set is analyzed. The analysis results are applied to
      the leader selection strategy, and make algorithm avoid trapping in local
      optimum. Moreover, a clustering solution-improved method is proposed, which can
      increase the efficiency in searching clustering solution greatly. In the
      experiments, 28 datasets are used and nine state-of-the-art clustering algorithms
      are compared, the proposed method is superior to other approaches in the
      evaluation index ARI.

PMID- 29206881
TI  - Deletion of lynx1 reduces the function of alpha6* nicotinic receptors.
AB  - The alpha6 nicotinic acetylcholine receptor (nAChR) subunit is an attractive drug
      target for treating nicotine addiction because it is present at limited sites in
      the brain including the reward pathway. Lynx1 modulates several nAChR subtypes;
      lynx1-nAChR interaction sites could possibly provide drug targets. We found that
      dopaminergic cells from the substantia nigra pars compacta (SNc) express lynx1
      mRNA transcripts and, as assessed by co-immunoprecipitation, alpha6 receptors
      form stable complexes with lynx1 protein, although co-transfection with lynx1 did
      not affect nicotine-induced currents from cell lines transfected with alpha6 and
      beta2. To test whether lynx1 is important for the function of alpha6 nAChRs in
      vivo, we bred transgenic mice carrying a hypersensitive mutation in the alpha6
      nAChR subunit (alpha6L9'S) with lynx1 knockout mice, providing a selective probe
      of the effects of lynx1 on alpha6* nAChRs. Lynx1 removal reduced the alpha6
      component of nicotine-mediated rubidium efflux and dopamine (DA) release from
      synaptosomal preparations with no effect on numbers of alpha6beta2 binding sites,
      indicating that lynx1 is functionally important for alpha6* nAChR activity. No
      effects of lynx1 removal were detected on nicotine-induced currents in slices
      from SNc, suggesting that lynx1 affects presynaptic alpha6* nAChR function more
      than somatic function. In the absence of agonist, lynx1 removal did not alter DA
      release in dorsal striatum as measured by fast scan cyclic voltammetry. Lynx1
      removal affected some behaviors, including a novel-environment assay and nicotine
      stimulated locomotion. Trends in 24-hour home-cage behavior were also suggestive
      of an effect of lynx1 removal. Conditioned place preference for nicotine was not
      affected by lynx1 removal. The results show that some functional and behavioral
      aspects of alpha6-nAChRs are modulated by lynx1.

PMID- 29206883
TI  - Watching TV has a distinct sociodemographic and lifestyle profile compared with
      other sedentary behaviors: A nationwide population-based study.
AB  - Watching TV has been consistently associated with higher risk of adverse health
      outcomes, but the effect of other sedentary behaviors (SB) is uncertain.
      Potential explanations are that watching TV is not a marker of a broader
      sedentary pattern and that each SB reflects different sociodemographic and health
      characteristics. Data were taken form a survey on 10,199 individuals,
      representative of the Spanish population aged >=18 years. SB and other health
      behaviors were ascertained using validated questionnaires. Watching TV was the
      predominant SB (45.4% of the total sitting time), followed by sitting at the
      computer (22.7%). TV watching time showed no correlation with total time on other
      SB (r: -0.02, p = 0.07). By contrast, time spent at the computer was directly
      correlated with time spent on commuting (r: 0.07, p<0.01), listening to music (r:
      0.10, p<0.01) and reading (r: 0.08, p<0.01). TV watching time was greater in
      those with older age, lower education, unhealthier lifestyle, and with diabetes
      or osteomuscular disease. More time spent at the computer or in commuting was
      linked to younger age, male gender, higher education and having a sedentary job.
      In conclusion, watching TV is not correlated with other SB and shows a distinct
      demographic and lifestyle profile.

PMID- 29206882
TI  - Morphological study of the eye and adnexa in capuchin monkeys (Sapajus sp.).
AB  - The objective of this study was to describe the anatomic and histologic features
      of the Sapajus sp. eye, comparing similarities and differences of humans and
      other species of non-human primates for biomedical research purposes. Computed
      tomography (CT) of adnexa, eye and orbit live animal, as well as formolized
      pieces of the same structures of Sapajus sp. for anatomical and histological
      study were also performed. The anatomical description of the eye and adnexa was
      performed using the techniques of topographic dissection and exenteration.
      Histological fragments were fixated in buffered formalin 10%, processed by the
      routine paraffin inclusion technique, stained with hematoxylin-eosin and special
      stains. CT scan evaluation showed no differences between the live animal and the
      formolized head on identification of visual apparatus structures. Anatomic and
      histologic evaluation revealed rounded orbit, absence of the supraorbital foramen
      and frontal notch, little exposure of the sclera, with slight pigmentation of the
      exposed area and marked pigmentation at the sclerocorneal junction. Masson's
      Trichrome revealed the Meibomian glands, the corneal epithelium and Bowman's
      membrane; in the choroid, melanocytes and Bruch's membrane were observed; and in
      the retina, cones and rods as well as, optic nerve, the lamina cribrosa of the
      nerve fibers bundles. Toluidine blue highlighted the membranes: Bowman, Descemet
      and the endothelium; in the choroid: melanocytes; and in the retina: nuclear
      layers and retinal pigment epithelium. In view of the observed results Sapajus
      sp. is an important experimental model for research in the ophthalmology field,
      which has been shown due to the high similarity of its anatomical and
      histological structures with the human species.

PMID- 29206884
TI  - Rapid research and implementation priority setting for wound care uncertainties.
AB  - INTRODUCTION: People with complex wounds are more likely to be elderly, living
      with multimorbidity and wound related symptoms. A variety of products are
      available for managing complex wounds and a range of healthcare professionals are
      involved in wound care, yet there is a lack of good evidence to guide practice
      and services. These factors create uncertainty for those who deliver and those
      who manage wound care. Formal priority setting for research and implementation
      topics is needed to more accurately target the gaps in treatment and services. We
      solicited practitioner and manager uncertainties in wound care and held a
      priority setting workshop to facilitate a collaborative approach to prioritising
      wound care-related uncertainties. METHODS: We recruited healthcare professionals
      who regularly cared for patients with complex wounds, were wound care specialists
      or managed wound care services. Participants submitted up to five wound care
      uncertainties in consultation with their colleagues, via an on-line survey and
      attended a priority setting workshop. Submitted uncertainties were collated,
      sorted and categorised according professional group. On the day of the workshop,
      participants were divided into four groups depending on their profession.
      Uncertainties submitted by their professional group were viewed, discussed and
      amended, prior to the first of three individual voting rounds. Participants cast
      up to ten votes for the uncertainties they judged as being high priority.
      Continuing in the professional groups, the top 10 uncertainties from each group
      were displayed, and the process was repeated. Groups were then brought together
      for a plenary session in which the final priorities were individually scored on a
      scale of 0-10 by participants. Priorities were ranked and results presented.
      Nominal group technique was used for generating the final uncertainties, voting
      and discussions. RESULTS: Thirty-three participants attended the workshop
      comprising; 10 specialist nurses, 10 district nurses, seven podiatrists and six
      managers. Participants had been qualified for a mean of 20.7 years with a mean of
      16.8 years of wound care experience. One hundred and thirty-nine uncertainties
      were submitted electronically and a further 20 were identified on the day of the
      workshop following lively, interactive group discussions. Twenty-five
      uncertainties from the total of 159 generated made it to the final prioritised
      list. These included six of the 20 new uncertainties. The uncertainties varied in
      focus, but could be broadly categorised into three themes: service delivery and
      organisation, patient centred care and treatment options. Specialist nurses were
      more likely to vote for service delivery and organisation topics, podiatrists for
      patient centred topics, district nurses for treatment options and operational
      leads for a broad range. CONCLUSIONS: This collaborative priority setting project
      is the first to engage front-line clinicians in prioritising research and
      implementation topics in wound care. We have shown that it is feasible to conduct
      topic prioritisation in a short time frame. This project has demonstrated that
      with careful planning and rigor, important questions that are raised in the
      course of clinicians' daily decision making can be translated into meaningful
      research and implementation initiatives that could make a difference to service
      delivery and patient care.

PMID- 29206885
TI  - Does elevated glucose metabolism correlate with higher cell density in
      Neurofibromatosis type 1 associated peripheral nerve sheath tumors?
AB  - PURPOSE: To investigate whether elevated glucose metabolism in neurofibroma,
      determined by [F18]-FDG-PET, is correlated with cell density in MRI, as expressed
      through the apparent diffusion coefficient. MATERIALS AND METHODS: Patients
      diagnosed with neurofibromatosis type 1 and peripheral nerve sheath tumors (PNST)
      were enrolled in this prospective, IRB-approved study. After a single [F18]-FDG
      injection, patients consecutively underwent [F18]-FDG-PET/CT and [F18]-FDG
      PET/MRI on the same day. Maximum and mean standardized uptake values (SUVmax,
      SUVmean) on [F18]-FDG-PET/CT and [F18]-FDG-PET/MRI were compared, and correlated
      with minimum and mean apparent diffusion coefficients (ADCmean, ADCmin). RESULTS:
      A total of 12 (6 male/6 female, mean age was 16.2 +/- 5.2 years) patients were
      prospectively included and analyzed on a per-lesion (n = 39) basis. The SUVmean
      of examined PNST showed a moderate negative correlation with the ADCmean (r = 
      .441) and ADCmin (r = -.477), which proved to be statistically significant (p =
      .005 and p = .002). The SUVmax of the respective lesions, however, showed a
      weaker negative correlation for ADCmean (r: -.311) and ADCmin (r: -.300) and did
      not reach statistical significance (p = .054 and p = .057). Lesion-based
      correlation between [F18]-FDG-PET/MRI and [F18]-FDG-PET/CT showed a moderate
      correlation for SUVmax (r = .353; p = .027) and a strong one for SUVmean (r =
      .879; p = .001)). Patient-based liver uptake (SUVmax and mean) of [F18]-FDG
      PET/MRI and [F18]-FDG-PET/CT were strongly positively correlated (r = .827; p <
      .001 and r = .721; p < .001) but differed significantly (p < .001). CONCLUSIONS:
      We found a statistically significant, negative correlation between glucose
      metabolism and cell density in PNST. Thus, ADCmean and ADCmin could possibly add
      complimentary information to the SUVmax and SUVmean and may serve as a potential
      determinant of malignant transformation of PNST.

PMID- 29206886
TI  - Monodisperse measurement of the biotin-streptavidin interaction strength in a
      well-defined pulling geometry.
AB  - The widely used interaction of the homotetramer streptavidin with the small
      molecule biotin has been intensively studied by force spectroscopy and has become
      a model system for receptor ligand interaction. However, streptavidin's
      tetravalency results in diverse force propagation pathways through the different
      binding interfaces. This multiplicity gives rise to polydisperse force
      spectroscopy data. Here, we present an engineered monovalent streptavidin
      tetramer with a single cysteine in its functional subunit that allows for site
      specific immobilization of the molecule, orthogonal to biotin binding.
      Functionality of streptavidin and its binding properties for biotin remain
      unaffected. We thus created a stable and reliable molecular anchor with a unique
      high-affinity binding site for biotinylated molecules or nanoparticles, which we
      expect to be useful for many single-molecule applications. To characterize the
      mechanical properties of the bond between biotin and our monovalent streptavidin,
      we performed force spectroscopy experiments using an atomic force microscope. We
      were able to conduct measurements at the single-molecule level with 1:1
      stoichiometry and a well-defined geometry, in which force exclusively propagates
      through a single subunit of the streptavidin tetramer. For different force
      loading rates, we obtained narrow force distributions of the bond rupture forces
      ranging from 200 pN at 1,500 pN/s to 230 pN at 110,000 pN/s. The data are in very
      good agreement with the standard Bell-Evans model with a single potential barrier
      at Deltax0 = 0.38 nm and a zero-force off-rate koff,0 in the 10-6 s-1 range.

PMID- 29206887
TI  - Reduced spore germination explains sensitivity of reef-building algae to climate
      change stressors.
AB  - Reduced seawater pH and changes in carbonate chemistry associated with ocean
      acidification (OA) decrease the recruitment of crustose coralline algae (CCAcf.),
      an important coral-reef builder. However, it is unclear whether the observed
      decline in recruitment is driven by impairment of spore germination, or post
      settlement processes (e.g. space competition). To address this, we conducted an
      experiment using a dominant CCA, Porolithon cf. onkodes to test the independent
      and combined effects of OA, warming, and irradiance on its germination success
      and early development. Elevated CO2 negatively affected several processes of
      spore germination, including formation of the germination disc, initial growth,
      and germling survival. The magnitude of these effects varied depending on the
      levels of temperature and irradiance. For example, the combination of high CO2
      and high temperature reduced formation of the germination disc, but this effect
      was independent of irradiance levels, while spore abnormalities increased under
      high CO2 and high temperature particularly in combination with low irradiance
      intensity. This study demonstrates that spore germination of CCA is impacted by
      the independent and interactive effects of OA, increasing seawater temperature
      and irradiance intensity. For the first time, this provides a mechanism for how
      the sensitivity of critical early life history processes to global change may
      drive declines of adult populations of key marine calcifiers.

PMID- 29206888
TI  - Corrigendum: Supported Discharge Teams for older people in hospital acute care: a
      randomized controlled trial.

PMID- 29206889
TI  - Drastic decrease of the HIV reservoir in a patient treated with nivolumab for
      lung cancer.

PMID- 29206890
TI  - Validation of the diagnosis of mesothelioma and BAP1 protein expression in a
      cohort of asbestos textile workers from Northern Italy.
AB  - Background: Diagnosis of mesothelioma based on death certificate is subject to
      misclassification, which may bias the results of epidemiology studies. A high
      proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1
      (BAP1) gene. Methods: We searched medical and pathology records and specimens for
      127 workers from a textile-asbestos factory in Italy who died during 1963-2013
      with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death
      certificate, to confirm the diagnosis with immunohistochemistry markers. We
      calculated the odds ratio of confirmation by selected characteristics and
      asbestos exposure variables. When sufficient pathology material was available, we
      analyzed BAP1 protein expression. Results: The diagnosis of mesothelioma was
      histologically confirmed for 35 cases (27.6%); 5 cases were classified as non
      mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record
      but no sufficient material was available for revision (26.0%); no records were
      available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation
      was not associated with sex, location of the neoplasm, age, or duration of
      employment; however, there was a significant association with time since first
      employment (P for linear trend 0.04). An association between duration of
      employment and time since first employment was observed for confirmed cases but
      not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases
      (51.4%), without an association with sex, location, age, indices of asbestos
      exposure, or survival. Conclusions: We were able to confirm by
      immunohistochemistry a small proportion of mesothelioma diagnoses on certificates
      of deceased asbestos workers, and confirmation correlated with latency of
      asbestos exposure but not other characteristics. BAP1 protein loss is a frequent
      event in mesothelioma of asbestos-exposed workers, but does not correlate with
      exposure.

PMID- 29206891
TI  - Rituximab: a benchmark in the development of chemotherapy-free treatment
      strategies for follicular lymphomas.
AB  - Background: With the introduction of the anti-CD20 antibody rituximab, the
      outcome of patients with follicular lymphoma (FL) has greatly improved over the
      last two decades. First-line prolonged rituximab monotherapy is effective,
      achieving long-term remission and prolonged failure-free survival in some
      patients. Additionally, rituximab has been shown to synergize with
      chemotherapeutic and novel targeted agents alike with measurable gains in
      duration of response. As such, rituximab has made its mark in the treatment of FL
      and remains a valid agent despite the availability of newer monoclonal
      antibodies. This review summarizes the evolving role of rituximab as the first
      available anti-CD20 monoclonal antibody, emphasizing its clear activity as a
      single agent and in combination with chemotherapy or molecular targeted agents,
      and setting the standard for the development of new anti-CD20 monoclonal
      antibodies. Conclusion: We provide data that support the ongoing use of rituximab
      as a therapeutic partner for novel agents in future clinical trials exploring
      chemotherapy-free alternatives.

PMID- 29206892
TI  - Progestin-associated shift of meningioma mutational landscape.
AB  - Background: Meningiomas are the most common primary tumor of the central nervous
      system. The relationship between meningioma and progestins is frequently
      mentioned but has not been elucidated. Patients and methods: We identified 40
      female patients operated for a meningioma after long-term progestin therapy and
      performed targeted next generation sequencing to decipher the mutational
      landscape of hormone-related meningiomas. A published cohort of 530 meningiomas
      in women was used as a reference population. Results: Compared with the control
      population of meningiomas in women, progestin-associated meningiomas were more
      frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and
      located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found
      a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8]
      and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower
      frequency of NF2-related tumors compared with the control population of
      meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift
      in mutational landscape indicates the vulnerability of certain meningeal cells
      and mutations to hormone-induced tumorigenesis. While the relationship between
      PIK3CA mutation frequency and hormone-related cancers such as breast and
      endometrial cancer is well-known, this hormonally induced mutational shift is a
      unique feature in molecular oncology.

PMID- 29206893
TI  - The cerebellar cognitive affective/Schmahmann syndrome scale.
AB  - Cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome) is
      characterized by deficits in executive function, linguistic processing, spatial
      cognition, and affect regulation. Diagnosis currently relies on detailed
      neuropsychological testing. The aim of this study was to develop an office or
      bedside cognitive screen to help identify CCAS in cerebellar patients. Secondary
      objectives were to evaluate whether available brief tests of mental function
      detect cognitive impairment in cerebellar patients, whether cognitive performance
      is different in patients with isolated cerebellar lesions versus complex
      cerebrocerebellar pathology, and whether there are cognitive deficits that should
      raise red flags about extra-cerebellar pathology. Comprehensive standard
      neuropsychological tests, experimental measures and clinical rating scales were
      administered to 77 patients with cerebellar disease-36 isolated cerebellar
      degeneration or injury, and 41 complex cerebrocerebellar pathology-and to healthy
      matched controls. Tests that differentiated patients from controls were used to
      develop a screening instrument that includes the cardinal elements of CCAS. We
      validated this new scale in a new cohort of 39 cerebellar patients and 55 healthy
      controls. We confirm the defining features of CCAS using neuropsychological
      measures. Deficits in executive function were most pronounced for working memory,
      mental flexibility, and abstract reasoning. Language deficits included verb for
      noun generation and phonemic > semantic fluency. Visual spatial function was
      degraded in performance and interpretation of visual stimuli. Neuropsychiatric
      features included impairments in attentional control, emotional control,
      psychosis spectrum disorders and social skill set. From these results, we derived
      a 10-item scale providing total raw score, cut-offs for each test, and pass/fail
      criteria that determined 'possible' (one test failed), 'probable' (two tests
      failed), and 'definite' CCAS (three tests failed). When applied to the
      exploratory cohort, and administered to the validation cohort, the
      CCAS/Schmahmann scale identified sensitivity and selectivity, respectively as
      possible exploratory cohort: 85%/74%, validation cohort: 95%/78%; probable
      exploratory cohort: 58%/94%, validation cohort: 82%/93%; and definite exploratory
      cohort: 48%/100%, validation cohort: 46%/100%. In patients in the exploratory
      cohort, Mini-Mental State Examination and Montreal Cognitive Assessment scores
      were within normal range. Complex cerebrocerebellar disease patients were
      impaired on similarities in comparison to isolated cerebellar disease. Inability
      to recall words from multiple choice occurred only in patients with extra
      cerebellar disease. The CCAS/Schmahmann syndrome scale is useful for expedited
      clinical assessment of CCAS in patients with cerebellar
      disorders.awx317media15678692096001.

PMID- 29206894
TI  - Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective
      Study.
AB  - Aim: Alcoholic liver disease (ALD) is the most common liver disease in the
      Western World. Liver transplantation (LT) is the treatment for end-stage ALD.
      However, many transplant centers are still reluctant to transplant these patients
      because of the risk of alcohol relapse, recurrence of the primary liver disease
      and associated post-transplant complications. We examined survival rate,
      prevalence of primary liver disease recurrence, re-transplantation and post
      transplant complications among transplanted patients for alcoholic cirrhosis
      compared with those transplanted for viral cirrhosis. Methods: data about
      patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital
      from January 1995 to April 2016 were retrospectively collected. Survival rate was
      evaluated according to the Kaplan-Meier method. Recurrence was defined as
      histological evidence of primary liver disease. Data on the onset of
      complication, causes of death and graft failure after liver transplant were
      analyzed. Results: There was no statistically significant difference regarding
      survival rate between the two groups. Only patients transplanted for viral
      cirrhosis presented with primary liver disease recurrence. There was a higher
      rate of cancer development in patients transplanted for alcoholic cirrhosis.
      Cancer was the major cause of death in this population. Risk factors associated
      with the onset of cancer were a high MELD score at the transplant time and
      smoking after transplantation. Conclusion: ALD is a good indication for LT.
      Patients transplanted for alcoholic cirrhosis should receive regular cancer
      screening and should be advised against smoking. Short Summary: No difference was
      found between patients transplanted for alcoholic cirrhosis and viral cirrhosis
      in term of survival rate. Only patients transplanted for viral cirrhosis
      presented primary liver disease recurrence. A higher rate of cancer development
      was found in patients transplanted for alcoholic cirrohosis. This complication
      was associated with post-trasplant smoking.

PMID- 29206896
TI  - Review of methodologies of cohort studies of older people.
AB  - This paper describes a cohort study in terms of its design, the research
      questions answered by cohort studies, common analytic techniques and the
      strengths and limitations of this type of study. We also describe the main cohort
      studies of older populations, many of which are available for secondary data
      analysis.

PMID- 29206895
TI  - Minimally conscious state or cortically mediated state?
AB  - Durable impairments of consciousness are currently classified in three main
      neurological categories: comatose state, vegetative state (also recently coined
      unresponsive wakefulness syndrome) and minimally conscious state. While the
      introduction of minimally conscious state, in 2002, was a major progress to help
      clinicians recognize complex non-reflexive behaviours in the absence of
      functional communication, it raises several problems. The most important issue
      related to minimally conscious state lies in its criteria: while behavioural
      definition of minimally conscious state lacks any direct evidence of patient's
      conscious content or conscious state, it includes the adjective 'conscious'. I
      discuss this major problem in this review and propose a novel interpretation of
      minimally conscious state: its criteria do not inform us about the potential
      residual consciousness of patients, but they do inform us with certainty about
      the presence of a cortically mediated state. Based on this constructive criticism
      review, I suggest three proposals aiming at improving the way we describe the
      subjective and cognitive state of non-communicating patients. In particular, I
      present a tentative new classification of impairments of consciousness that
      combines behavioural evidence with functional brain imaging data, in order to
      probe directly and univocally residual conscious processes.

PMID- 29206897
TI  - Optimization of Poplar mRNA purification for trancriptome library construction.

PMID- 29206898
TI  - Somatic mutation footprinting reveals a unique tetranucleotide signature
      associated with intron-exon boundaries in lung cancer.
AB  - Cigarette smoke comprises a large number of carcinogenic substances that can
      increase DNA mutation load in epithelial cells of the mouth, throat and lungs.
      While a strong C:A substitution preference is abundant in tobacco-related cancer
      genomes, detection of complex or less abundant somatic mutation signatures may be
      confounded by the heterogeneity of carcinogens present in smoke. Trinucleotide
      signatures are defined for a variety of somatic mutation processes, yet the
      extent to which this configuration optimally defines and discriminates between
      mutational processes is not clear. Here, we describe a method that determines
      whether trinucleotide patterns do a good job at encapsulating a mutation
      signature or whether they mask underlying heterogeneity that alternative pattern
      structures would better define. The approach works by mapping the dependency of
      trinucleotide signatures in relation to sequence context to establish a
      'footprint' of context dependency. Applying this technique to smoke-associated
      cancers, we show that a robust tetranucleotide substitution is prevalent in 17%
      of lung squamous cell carcinoma genomes. The signature is dominated by the
      substitution CT(C:A)G and is strongly associated with gene expression level and
      intron-exon junctions. Intriguingly, its distribution across the genome is biased
      towards 5' splice junctions, suggesting a novel mechanism of mutation.

PMID- 29206899
TI  - MOSAIC: a chemical-genetic interaction data repository and web resource for
      exploring chemical modes of action.
AB  - Summary: Chemical-genomic approaches that map interactions between small
      molecules and genetic perturbations offer a promising strategy for functional
      annotation of uncharacterized bioactive compounds. We recently developed a new
      high-throughput platform for mapping chemical-genetic (CG) interactions in yeast
      that can be scaled to screen large compound collections, and we applied this
      system to generate CG interaction profiles for more than 13 000 compounds. When
      integrated with the existing global yeast genetic interaction network, CG
      interaction profiles can enable mode-of-action prediction for previously
      uncharacterized compounds as well as discover unexpected secondary effects for
      known drugs. To facilitate future analysis of these valuable data, we developed a
      public database and web interface named MOSAIC. The website provides a convenient
      interface for querying compounds, bioprocesses (Gene Ontology terms) and genes
      for CG information including direct CG interactions, bioprocesses and gene-level
      target predictions. MOSAIC also provides access to chemical structure information
      of screened molecules, chemical-genomic profiles and the ability to search for
      compounds sharing structural and functional similarity. This resource will be of
      interest to chemical biologists for discovering new small molecule probes with
      specific modes-of-action as well as computational biologists interested in
      analysing CG interaction networks. Availability and implementation: MOSAIC is
      available at http://mosaic.cs.umn.edu. Contact: hisyo@riken.jp,
      yoshidam@riken.jp, charlie.boone@utoronto.ca or chadm@umn.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29206900
TI  - Cbx3 inhibits vascular smooth muscle cell proliferation, migration, and neointima
      formation.
AB  - Aims: To investigate the role of chromobox protein homolog 3 (Cbx3) in vascular
      smooth muscle cell (VSMC) proliferation, migration, and neointima formation
      following vascular injury. Methods and results: Overexpression of Cbx3 led to a
      significant increase in VSMC contractile gene expression and VSMC apoptosis as
      well as a dramatic decrease in collagen gene expression, VSMC proliferation, and
      migration. Meanwhile, the opposite was observed following inhibition of
      endogenous Cbx3. Luciferase activity assays revealed that Notch signalling, but
      neither beta-catenin nor NF-kappaB signalling, is regulated by Cbx3 in VSMCs, and
      among the four Notch receptors, Notch3 is selectively down-regulated by Cbx3
      through a transcriptional repression mechanism. Notch3 gene activation
      recapitulates the effects of Cbx3 knockdown on VSMC proliferation and migration.
      Consequently, the inhibitory effects of Cbx3 over-expression on VSMC
      proliferation and migration were reversed by Notch3 gene reactivation. In a model
      of vascular damage by carotid wire injury, we observed that Cbx3 expression was
      dramatically down-regulated in the injured arteries. Local ectopic over
      expression of Cbx3 in the injured arteries significantly inhibited Notch3
      expression, thereby reducing VSMCs proliferation and causing an overall decrease
      in neointima formation. Additionally, injury-induced neointimal SMC hyperplasia
      was significantly reduced by aortic inhibition of Notch3. Importantly, a
      decreased expression level of Cbx3, but an increased expression level of Notch3,
      was observed in human femoral arteries with atherosclerotic lesions. Conclusion:
      Cbx3 modulates VSMC contractile and collagen gene expression, as well as VSMC
      proliferation, migration, and apoptosis via a Notch3 pathway, and plays an
      important role in controlling injury-induced neointima formation.

PMID- 29206901
TI  - GenSSI 2.0: multi-experiment structural identifiability analysis of SBML models.
AB  - Motivation: Mathematical modeling using ordinary differential equations is used
      in systems biology to improve the understanding of dynamic biological processes.
      The parameters of ordinary differential equation models are usually estimated
      from experimental data. To analyze a priori the uniqueness of the solution of the
      estimation problem, structural identifiability analysis methods have been
      developed. Results: We introduce GenSSI 2.0, an advancement of the software
      toolbox GenSSI (Generating Series for testing Structural Identifiability). GenSSI
      2.0 is the first toolbox for structural identifiability analysis to implement
      Systems Biology Markup Language import, state/parameter transformations and multi
      experiment structural identifiability analysis. In addition, GenSSI 2.0 supports
      a range of MATLAB versions and is computationally more efficient than its
      previous version, enabling the analysis of more complex models. Availability and
      implementation: GenSSI 2.0 is an open-source MATLAB toolbox and available at
      https://github.com/genssi-developer/GenSSI. Contact: thomas.ligon@physik.uni
      muenchen.de or jan.hasenauer@helmholtz-muenchen.de. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29206903
TI  - Rapid Determination of Pyrrolidinium Cations by Ion-Pair Chromatography With
      Imidazolium Ionic Liquids.
AB  - This article describes a pioneering ion-pair chromatography with indirect
      ultraviolet detection with imidazolium ionic liquids (ILs) as ultraviolet
      absorption reagent and eluting agent for determination of pyrrolidinium cations.
      Three pyrrolidinium cations were analyzed on a reversed-phase silica-based
      monolithic column by isocratic elution with imidazolium ILs-ion-pair reagents
      methanol mixtures. The effects of the ultraviolet absorption reagents, detection
      wavelength, ion-pair reagents, imidazolium ILs, organic solvents, column
      temperature and flow rate on the separation and determination of pyrrolidinium
      cations were investigated. Under the selected chromatographic conditions, the
      separation time was reduced to <2.5 min while maintaining excellent peak shapes
      and sufficient resolution. The detection limits for N-methyl-N-ethylpyrrolidinium
      cation, N-methyl-N-propylpyrrolidinium cation and N-methyl-N-butylpyrrolidinium
      cation were 0.12, 0.08 and 0.19 mg/L, respectively. Relative standard deviations
      for peak area were <0.59%. This simple and practical method has been successfully
      applied to the determination of three IL samples synthesized by the chemistry
      laboratory. The method is accurate, reliable and meets the requirements for
      quantitative analysis. In general, the analytical system and its associated
      methods appear to be widely applicable to determination of pyrrolidinium cations.

PMID- 29206902
TI  - Managing Asbestos-Containing Materials in the Built Environment: Report of a
      Health and Safety Executive and Government Office for Science Workshop.
AB  - The duty to manage asbestos in non-domestic premises is described in the Control
      of Asbestos Regulations 2012. Health and Safety Executive (HSE) policy and
      guidance on asbestos in the built environment in Great Britain is that asbestos
      containing materials (ACMs) that are in good condition and unlikely to be
      disturbed can be managed in place. Where ACMs are in poor condition or likely to
      be disturbed they should be repaired, encapsulated or, if necessary, removed. HSE
      and Government Office for Science hosted a stakeholder workshop to consider
      evidence on the management of ACMs in public buildings. Invitees attended from a
      range of backgrounds (including regulatory, government, academic, medical, public
      interest groups, and professional service providers). Participants considered the
      evidence, suggested nine evidence gap areas and ranked these according to
      preference in an anonymous vote. The top three suggested evidence gaps were: (i)
      the comparative risks of managing ACMs in place versus removal; (ii) improved
      measurement techniques at lower fibre concentrations; and (iii) building the
      evidence base on the effectiveness of asbestos management and safe removal. HSE
      will use the workshop outputs to inform its research planning. It is anticipated
      that a number of initiatives for shared research will be explored.

PMID- 29206904
TI  - The ESMO Precision Medicine Glossary.

PMID- 29206906
TI  - What is Comprehensive Geriatric Assessment (CGA)? An umbrella review.
AB  - Background: Comprehensive Geriatric Assessment (CGA) is now the accepted gold
      standard for caring for frail older people in hospital. However, there is
      uncertainty about identifying and targeting suitable recipients and which
      patients benefit the most. Objectives: our objectives were to describe the key
      elements, principal measures of outcome and the characteristics of the main
      beneficiaries of inpatient CGA. Methods: we used the Joanna Briggs Institute
      umbrella review method. We searched for systematic reviews and meta-analyses
      describing CGA services for hospital inpatients in the Cochrane Database of
      Systematic Reviews, Database of Reviews of Effectiveness (DARE), MEDLINE and
      EMBASE and a range of other sources. Results: we screened 1,010 titles and
      evaluated 419 abstracts for eligibility, 143 full articles for relevance and
      included 24 in a final quality and relevance check. Thirteen reviews, reported in
      15 papers, were selected for review. The most widely used definition of CGA was:
      'a multidimensional, multidisciplinary process which identifies medical, social
      and functional needs, and the development of an integrated/co-ordinated care plan
      to meet those needs'. Key clinical outcomes included mortality, activities of
      daily living and dependency. The main beneficiaries were people >=55 years in
      receipt of acute care. Frailty in CGA recipients and patient related outcomes
      were not usually reported. Conclusions: we confirm a widely used definition of
      CGA. Key outcomes are death, disability and institutionalisation. The main
      beneficiaries in hospital are older people with acute illness. The presence of
      frailty has not been widely examined as a determinant of CGA outcome.

PMID- 29206905
TI  - Control of inflammation decreases the need for subsequent esophageal dilation in
      patients with eosinophilic esophagitis.
AB  - It is unknown if successful control of esophageal inflammation in eosinophilic
      esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed
      to determine whether histologic response to topical steroid treatment decreases
      the likelihood and frequency of subsequent esophageal dilation. We conducted a
      retrospective cohort study. Patients with an incident diagnosis of EoE were
      included if they had an initial esophageal dilation, received topical steroids,
      and had a subsequent endoscopy with biopsies. The number of dilations performed
      in each group was determined, and histologic responders (<15 eos/hpf) were
      compared to nonresponders. The 55 EoE patients included (27 responders and 28
      nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19
      months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P =
      0.03), after adjusting for potential confounders. Despite undergoing
      significantly fewer dilations, responders achieved a similar increase in
      esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients
      undergoing esophageal dilation at baseline, control of inflammation with topical
      steroids was associated with a 65% decrease in the number of subsequent dilations
      to maintain the same esophageal caliber. This suggests that inflammation control
      is an important goal in patients with fibrostenotic changes of EoE.

PMID- 29206907
TI  - A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal
      tumor development in ApcDelta14/+ mice.
AB  - Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the
      development of hundreds of polyps throughout the colon. Without prophylactic
      colectomy, most individuals with FAP develop colorectal cancer at an early age.
      Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce
      polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid
      oxidation, a stable form of EPA compound has been developed in the form of
      magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the
      chemopreventive efficacy of TP-252 on intestinal tumor formation using
      ApcDelta14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a
      modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and
      administered to mice for 11 weeks. We found that administration of TP-252
      significantly reduced tumor number and size in the small intestine and colon in a
      dose-related manner and as effectively as EPA-FFA. To gain further insight into
      the cancer protection afforded to the colon, we performed a comprehensive
      lipidomic analysis of total fatty acid composition and eicosanoid metabolites.
      Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA)
      and increased EPA concentrations within the colonic mucosa. Furthermore, a
      classification and regression tree (CART) analysis revealed that a subset of
      fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream
      metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were
      strongly associated with antineoplastic activity. These results indicate that TP
      252 warrants further clinical development as a potential strategy for delaying
      colectomy in adolescent FAP patients.

PMID- 29206908
TI  - Regulatory and Operational Complexities of Conducting a Clinical Treatment Trial
      During an Ebola Virus Disease Epidemic.
AB  - The first phase II and III clinical trials for Ebola virus disease treatments
      were conducted during the West Africa outbreak. We report the operational
      practicalities of conducting a phase II clinical trial of TKM-130803 to
      international standards during this outbreak.

PMID- 29206909
TI  - Seasonal Incidence of Symptomatic Influenza in the United States.
AB  - Background: The seasonal incidence of influenza is often approximated as 5%-20%.
      Methods: We used 2 methods to estimate the seasonal incidence of symptomatic
      influenza in the United States. First, we made a statistical estimate
      extrapolated from influenza-associated hospitalization rates for 2010-2011 to
      2015-2016, collected as part of national surveillance, covering approximately 9%
      of the United States, and including the existing mix of vaccinated and
      unvaccinated persons. Second, we performed a literature search and meta-analysis
      of published manuscripts that followed cohorts of subjects during 1996-2016 to
      detect laboratory-confirmed symptomatic influenza among unvaccinated persons; we
      adjusted this result to the US median vaccination coverage and effectiveness
      during 2010-2016. Results: The statistical estimate of influenza incidence among
      all ages ranged from 3.0%-11.3% among seasons, with median values of 8.3% (95%
      confidence interval [CI], 7.3%-9.7%) for all ages, 9.3% (95% CI, 8.2%-11.1%) for
      children <18 years, and 8.9% (95% CI, 8.2%-9.9%) for adults 18-64 years.
      Corresponding values for the meta-analysis were 7.1% (95% CI, 6.1%-8.1%) for all
      ages, 8.7% (95% CI, 6.6%-10.5%) for children, and 5.1% (95% CI, 3.6%-6.6%) for
      adults. Conclusions: The 2 approaches produced comparable results for children
      and persons of all ages. The statistical estimates are more versatile and permit
      estimation of season-to-season variation. During 2010-2016, the incidence of
      symptomatic influenza among vaccinated and unvaccinated US residents, including
      both medically attended and nonattended infections, was approximately 8% and
      varied from 3% to 11% among seasons.

PMID- 29206910
TI  - State Medicaid Hepatitis C Treatment Eligibility Criteria and Use of Direct
      Acting Antivirals.
AB  - Medicaid program criteria for accessing hepatitis C treatment are changing.
      Medicaid drug utilization data from 2014 to 2016 show that programs that have
      relaxed their criteria have seen significant increases in treatment utilization,
      as have states with Medicaid expansions.

PMID- 29206911
TI  - Libman-Sacks vegetations detected by 3D echocardiography.

PMID- 29206912
TI  - An evidence-based framework on community-centred approaches for health: England,
      UK.
AB  - Community participation is a central concept for health promotion, covering a
      breadth of approaches, purposes and activities. This paper reports on a national
      knowledge translation project in England, UK, which resulted in a conceptual
      framework and typology of community-based approaches, published as national
      guidance. A key objective was to develop a conceptual framework linked to sources
      of evidence that could be used to support increased uptake of participatory
      methods across the health system. It was recognized that legitimacy of community
      participation was being undermined by a scattered evidence base, absence of a
      common terminology and low visibility of community practice. A scoping review,
      combined with stakeholder consultation, was undertaken and 168 review and
      conceptual publications were identified and a map produced. A 'family of
      community-centred approaches for health and wellbeing' was then produced as way
      of organizing the evidence and visually representing the range of intervention
      types. There are four main groups, with sub-categories: (i) strengthening
      communities, (ii) volunteer and peer roles, (iii) collaborations and partnerships
      and (iv) access to community resources. Each group is differentiated using key
      concepts and theoretical justifications around increasing equity, control and
      social connectedness. An open access bibliography is available to accompany the
      framework. The paper discusses the application of the family of community-centred
      approaches as a flexible planning tool for health promotion practice and its
      potential to be used as a framework for organizing and synthesizing evidence from
      a range of participatory methods.

PMID- 29206913
TI  - Molecular regulation of Nodal signaling during mesendoderm formation.
AB  - One of the most important events during vertebrate embryogenesis is the formation
      or specification of the three germ layers, endoderm, mesoderm, and ectoderm.
      After a series of rapid cleavages, embryos form the mesendoderm and ectoderm
      during late blastulation and early gastrulation. The mesendoderm then further
      differentiates into the mesoderm and endoderm. Nodal, a member of the
      transforming growth factor beta (TGF-beta) superfamily, plays a pivotal role in
      mesendoderm formation by regulating the expression of a number of critical
      transcription factors, including Mix-like, GATA, Sox, and Fox. Because the Nodal
      signal transduction pathway is well-characterized, increasing effort has been
      made to delineate the spatiotemporal modulation of Nodal signaling during
      embryonic development. In this review, we summarize the recent progress
      delineating molecular regulation of Nodal signal intensity and duration during
      mesendoderm formation.

PMID- 29206914
TI  - Simultaneous Determination of Vinpocetine and its Major Active Metabolite
      Apovincaminic Acid in Rats by UPLC-MS/MS and its Application to the Brain Tissue
      Distribution Study.
AB  - A specific, rapid and sensitive ultra-performance liquid chromatography-tandem
      mass spectrometric (UPLC-MS/MS) method was developed for simultaneous
      determination of vinpocetine (VP) and its active metabolite, apovincaminic acid
      (AVA) in rat brain regions, such as hypothalamus, striatum, cortex, cerebellum
      and hippocampus. Phenacetin was used as internal standard (IS). Brain tissue
      samples were precipitated protein by using 500 MUL methanol. The separation was
      achieved on a Waters ACQUITY UPLC BEH C18 column (100 mm * 2.1 mm, 1.7 MUm),
      using a methanol-water gradient elution at the flow rate of 0.20 mL/min. The
      detection was performed on a triple quadrupole tandem mass spectrometer in
      multiple reaction monitoring (MRM) mode via positive electrospray ionization
      source (ESI). The quantification was operated using the transitions of m/z 351 ->
      m/z 280 for VP, m/z 323 -> m/z 280 for AVA and m/z 180 -> m/z 110 for IS,
      respectively. The calibration curve was linear in concentration range from 0.100
      to 60.0 ng/mL for VP and 0.103 to 6.18 ng/mL for AVA. The intra-day and inter-day
      precision (relative standard deviation, RSD) values were within 11.8%, the
      accuracy (relative error, RE) was from -1.7% to 3.0% for VP and 2.7% to 9.5% for
      AVA at all the three concentration levels of quality-control (QC) samples. The
      improved UPLC-MS/MS method was specific, rapid and sensitive, which was further
      successfully applied to simultaneous determination of VP and AVA in different rat
      brain regions after intragastric administration of 4 mg/kg VP. It was indicated
      that VP could be eliminated quickly in brain, while the elimination of AVA was
      slow and it could be maintained for more than 12 h in brain. Moreover, it was
      found that the contents of VP and AVA were much higher in the hypothalamus,
      striatum and cortex than those in the cerebellum and hippocampus, which verified
      the distribution characteristics of VP and AVA in different brain regions from
      the point of quantitation in rats.

PMID- 29206916
TI  - Regulation of low-density lipoprotein cholesterol by intestinal inflammation and
      the acute phase response.
AB  - Systemic inflammation, induced by disease or experimental intervention, is well
      established to result in elevated levels of circulating triglycerides, and
      reduced levels of high-density lipoprotein-cholesterol (HDL-C), in most mammalian
      species. However, the relationship between inflammation and low-density
      lipoprotein-cholesterol (LDL-C) concentrations is less clear. Most reports
      indicate that systemic inflammation, as observed during sepsis or following high
      dose experimental endotoxaemia, lowers total, and LDL-C in man. However, isolated
      reports have suggested that certain inflammatory conditions are associated with
      increased LDL-C. In this review, we summarize the emerging evidence that low
      grade inflammation specifically of intestinal origin may be associated with
      increased serum LDL-C levels. Preliminary insights into potential mechanisms that
      may mediate these effects, including those connecting inflammation to trans
      intestinal cholesterol efflux (TICE), are considered. We conclude that this
      evidence supports the potential downregulation of major mediators of TICE by
      inflammatory mediators in vitro and during intestinal inflammation in vivo. The
      TICE-inflammation axis therefore merits further study in terms of its potential
      to regulate serum LDL-C, and as a readily druggable target for
      hypercholesterolaemia.

PMID- 29206915
TI  - Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme
      Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc.
AB  - The enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH) is responsible for the
      synthesis of N-glycolylneuraminic acid (Neu5Gc), a sialic acid present on the
      cell surface proteins of most deuterostomes. The CMAH gene is thought to be
      present in most deuterostomes, but it has been inactivated in a number of
      lineages, including humans. The inability of humans to synthesize Neu5Gc has had
      several evolutionary and biomedical implications. Remarkably, Neu5Gc is a
      xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red
      meats, may promote inflammation, arthritis, and cancer. Likewise,
      xenotransplantation of organs producing Neu5Gc can result in inflammation and
      organ rejection. Therefore, knowing what animal species contain a functional CMAH
      gene, and are thus capable of endogenous Neu5Gc synthesis, has potentially far
      reaching implications. In addition to humans, other lineages are known, or
      suspected, to have lost CMAH; however, to date reports of absent and pseudogenic
      CMAH genes are restricted to a handful of species. Here, we analyze all available
      genomic data for nondeuterostomes, and 322 deuterostome genomes, to ascertain the
      phylogenetic distribution of CMAH. Among nondeuterostomes, we found CMAH homologs
      in two green algae and a few prokaryotes. Within deuterostomes, putatively
      functional CMAH homologs are present in 184 of the studied genomes, and a total
      of 31 independent gene losses/pseudogenization events were inferred. Our work
      produces a list of animals inferred to be free from endogenous Neu5Gc based on
      the absence of CMAH homologs and are thus potential candidates for human
      consumption, xenotransplantation research, and model organisms for investigation
      of human diseases.

PMID- 29206918
TI  - Differences in planktonic microbial communities associated with three types of
      macrophyte stands in a shallow lake.
AB  - Little is known about how various substances from living and decomposing aquatic
      macrophytes affect the horizontal patterns of planktonic bacterial communities.
      Study sites were located within Lake Kolon, which is a freshwater marsh and can
      be characterised by open-water sites and small ponds with different
      macrovegetation (Phragmites australis, Nymphea alba and Utricularia vulgaris).
      Our aim was to reveal the impact of these macrophytes on the composition of the
      planktonic microbial communities using comparative analysis of environmental
      parameters, microscopy and pyrosequencing data. Bacterial 16S rRNA gene sequences
      were dominated by members of phyla Proteobacteria (36%-72%), Bacteroidetes (12%
      33%) and Actinobacteria (5%-26%), but in the anoxic sample the ratio of Chlorobi
      (54%) was also remarkable. In the phytoplankton community, Cryptomonas sp.,
      Dinobryon divergens, Euglena acus and chrysoflagellates had the highest
      proportion. Despite the similarities in most of the measured environmental
      parameters, the inner ponds had different bacterial and algal communities,
      suggesting that the presence and quality of macrophytes directly and indirectly
      controlled the composition of microbial plankton.

PMID- 29206919
TI  - Identification and Quantification of Four Anthraquinones in Rhubarb and its
      Preparations by Gas Chromatography-Mass Spectrometry.
AB  - A gas chromatographic-mass spectrometric (GC-MS) method was developed for the
      determination of four anthraquinones found in rhubarb. Chrysophanol, physcion,
      aloe-emodin and emodin were confirmed by GC-MS and the possible main cleavage
      pathways of fragment ions are discussed in this study. Rhubarb is a traditional
      Chinese medicinal herb which required an effective evaluation method to
      quantitate the four major active anthraquinone compounds described. The
      determinations of analytes were accomplished by GC-MS using osthole as an
      internal standard. MS detection was performed in selected ion monitoring mode to
      increase the sensitivity. The method was evaluated by a number of validation
      characteristics (precision, limit of detection, calibration range and recovery).
      The calibration ranges were all 3.2-30.0 MUg/mL. This method was fully validated
      and showed good performances in terms of recovery (96.9-102.9%) and precision
      (1.4-2.9%). Finally, the method was applied to the analysis of four
      anthraquinones in rhubarb and its preparations in the first time.

PMID- 29206917
TI  - Tunicamycin-induced ER stress in breast cancer cells neither expresses GRP78 on
      the surface nor secretes it into the media.
AB  - GRP78 (an Mr 78 kDa calcium dependent glucose binding protein) is located in ER
      lumen. It functions as ER chaperone and translocates proteins for glycosylation
      at the asparagine residue present in the sequon Asn-X-Ser/Thr. Paraffin sections
      from N-glycosylation inhibitor tunicamycin treated ER-/PR-/HER2+ (double
      negative) breast tumor in athymic nude mice exhibited reduced N-glycan but
      increased GRP78 expression. We have evaluated the effect of tunicamycin on
      cellular localization of GRP78 in metastatic human breast cancer cells MDA-MB-231
      (ER-/PR-/HER2-). Tunicamycin inhibited cell proliferation in a time and dose
      dependent manner. Nonmetastatic estrogen receptor positive (ER+) MCF-7 breast
      cancer cells were also equally effective. GRP78 expression (protein and mRNA) was
      higher in tunicamycin (1.0 MUg/mL) treated MCF-7 and MDA-MB-231 cells. GRP78 is
      an ER stress marker, so we have followed its intracellular localization using
      immunofluorescence microscopy after subjecting the cancer cells to various stress
      conditions. Unfixed cells stained with either FITC-conjugated Concanavalin A (Con
      A) or Texas-red conjugated wheat germ agglutinin (WGA) exhibited surface
      expression of N-glycans but not GRP78. GRP78 became detectable only after a brief
      exposure of cells to ice-cold methanol. Western blotting did not detect GRP78 in
      conditioned media of cancer cells whereas it did for MMP-1. The conclusion, GRP78
      is expressed neither on the outer-leaflet of the (ER-/PR-/HER2-) human breast
      cancer cells nor it is secreted into the culture media during tunicamycin-induced
      ER stress. Our study therefore suggests strongly that anti-tumorigenic action of
      tunicamycin can be modeled to develop next generation cancer therapy, i.e.,
      glycotherapy for treating breast and other sold tumors.

PMID- 29206920
TI  - Evaluation of hospital readmissions for surgical site infections in Italy.
AB  - Background: The objectives of this investigation are to assess the prevalence of
      hospital readmissions for surgical site infections (SSIs) in patients aged >=18
      in Italy and to describe the clinical characteristics of these patients and
      evaluate the possible association with readmission for SSIs. Methods: A
      retrospective epidemiological study was conducted between January and May 2015
      considering a sample of patients aged >=18 years admitted to the surgical wards
      of two hospitals in Naples and undergoing surgery in the year 2014. Results: 3.8%
      of patients had been readmitted and 28.8% of them were readmitted to hospital due
      to SSIs. The multiple logistic regression model showed that readmissions for SSIs
      were significantly more common in smokers (odds ratio [OR] = 3.14; 95% confidence
      interval [CI] = 1.13-8.69), in patients with immunosuppression status (OR = 8.28;
      95% CI = 1.76-38.87), in patients with low serum albumin (OR = 3.07; 95% CI =
      1.05-9.01) and in patients who had undergone a surgical procedure classified as
      contaminated (OR = 10:44; 95% CI = 3.11-35.01) compared with those that had
      undergone a surgical procedure classified as clean. Conclusions: The results
      point to the need that hospital infection prevention strategies are implemented
      in order to reduce morbidity and mortality for patients. Moreover, the measures
      taken to prevent infections would lead to a reduction in health spending since
      almost one third of readmissions to the hospital in our study were due to SSIs.

PMID- 29206922
TI  - PIE: A prior knowledge guided integrated likelihood estimation method for bias
      reduction in association studies using electronic health records data.
AB  - Objectives: This study proposes a novel Prior knowledge guided Integrated
      likelihood Estimation (PIE) method to correct bias in estimations of associations
      due to misclassification of electronic health record (EHR)-derived binary
      phenotypes, and evaluates the performance of the proposed method by comparing it
      to 2 methods in common practice. Methods: We conducted simulation studies and
      data analysis of real EHR-derived data on diabetes from Kaiser Permanente
      Washington to compare the estimation bias of associations using the proposed
      method, the method ignoring phenotyping errors, the maximum likelihood method
      with misspecified sensitivity and specificity, and the maximum likelihood method
      with correctly specified sensitivity and specificity (gold standard). The
      proposed method effectively leverages available information on phenotyping
      accuracy to construct a prior distribution for sensitivity and specificity, and
      incorporates this prior information through the integrated likelihood for bias
      reduction. Results: Our simulation studies and real data application demonstrated
      that the proposed method effectively reduces the estimation bias compared to the
      2 current methods. It performed almost as well as the gold standard method when
      the prior had highest density around true sensitivity and specificity. The
      analysis of EHR data from Kaiser Permanente Washington showed that the estimated
      associations from PIE were very close to the estimates from the gold standard
      method and reduced bias by 60%-100% compared to the 2 commonly used methods in
      current practice for EHR data. Conclusions: This study demonstrates that the
      proposed method can effectively reduce estimation bias caused by imperfect
      phenotyping in EHR-derived data by incorporating prior information through
      integrated likelihood.

PMID- 29206921
TI  - Acute Effects of Methylphenidate, Modafinil, and MDMA on Negative Emotion
      Processing.
AB  - Background: Stimulants such as methylphenidate and modafinil are frequently used
      as cognitive enhancers in healthy people, whereas 3,4
      methylenedioxymethamphetamine (ecstasy) is proposed to enhance mood and empathy
      in healthy subjects. However, comparative data on the effects of methylphenidate
      and modafinil on negative emotions in healthy subjects have been partially
      missing. The aim of this study was to compare the acute effects of
      methylphenidate and modafinil on the neural correlates of fearful face processing
      using 3,4-methylenedioxymethamphetamine as a positive control. Methods: Using a
      double-blind, within-subject, placebo-controlled, cross-over design, 60 mg
      methylphenidate, 600 mg modafinil, and 125 mg 3,4-methylenedioxymethamphetamine
      were administrated to 22 healthy subjects while performing an event-related fMRI
      task to assess brain activation in response to fearful faces. Negative mood
      states were assessed with the State-Trait Anxiety Inventory and subjective
      ratings. Results: Relative to placebo, modafinil, but not methylphenidate or 3,4
      methylenedioxymethamphetamine, increased brain activation within a limbic
      cortical-striatal-pallidal-thalamic circuit during fearful face processing.
      Modafinil but not methylphenidate also increased amygdala responses to fearful
      faces compared with 3,4-methylenedioxymethamphetamine. Furthermore, activation in
      the middle and inferior frontal gyrus in response to fearful faces correlated
      positively with subjective feelings of fearfulness and depressiveness after
      modafinil administration. Conclusions: Despite the cognitive enhancement effects
      of 600 mg modafinil in healthy people, potential adverse effects on emotion
      processing should be considered.

PMID- 29206924
TI  - Predicting Australia's university students' mental health status.
AB  - University years are a period of increased morbidity and mortality, associated
      with negative health behaviours and corresponding poor mental health (MH) status
      amongst students. With this said, the aim of this research was to determine the
      level of influence a number of predictive factors have on Australia's university
      students' MH status. A cross-sectional study design, consisting of an online
      survey was implemented. Psychometric measurement components were based on
      adopting Bronfenbrenner's socio-ecological model approach to collecting
      descriptive statistics. This approach was concerned with investigating patterns
      of association between three predictive factors [social emotional wellbeing
      (SEWB), physical activity (PA) levels and sporting club (SC) involvement],
      against four domains (personal, university, home and community). This study
      identified that 25% (n = 571) of participants (n = 2326) indicated that they have
      been diagnosed with a MH disorder. Specifically, gender, age, negative health
      behaviours, lower levels of PA and SC involvement and poor SEWB, were found to be
      significantly and positively associated (p < 0.05*, p < 0.01**) with a MH
      diagnosis. Importantly, findings from this study indicate that there are
      significant (positive/negative) associations between the identified predictive
      factors and participants' MH status. Findings from this study will go towards
      informing current and future Student Health Service policies, practices and
      infrastructure allocation that address MH status amongst university students.

PMID- 29206925
TI  - Exploring fish microbial communities to mitigate emerging diseases in
      aquaculture.
AB  - Aquaculture is the fastest growing animal food sector worldwide and expected to
      further increase to feed the growing human population. However, existing and (re
      )emerging diseases are hampering fish and shellfish cultivation and yield. For
      many diseases, vaccination protocols are not in place and the excessive use of
      antibiotics and other chemicals is of substantial concern. A more sustainable
      disease control strategy to protect fish and shellfish from (re-)emerging
      diseases could be achieved by introduction or augmentation of beneficial
      microbes. To establish and maintain a 'healthy' fish microbiome, a fundamental
      understanding of the diversity and temporal-spatial dynamics of fish-associated
      microbial communities and their impact on growth and health of their aquatic
      hosts is required. This review describes insights in the diversity and functions
      of the fish bacterial communities elucidated with next-generation sequencing and
      discusses the potential of the microbes to mitigate (re-)emerging diseases in
      aquaculture.

PMID- 29206923
TI  - Vascular abnormalities in the placenta of Chst14-/- fetuses: implications in the
      pathophysiology of perinatal lethality of the murine model and vascular lesions
      in human CHST14/D4ST1 deficiency.
AB  - Collagen is one of the most important components of the extracellular matrix that
      is involved in the strength of tissues, cell adhesion and cell proliferation.
      Mutations in several collagen and post-translational modification enzyme genes
      cause Ehlers-Danlos syndrome (EDS) characterized by joint and skin
      hyperextensibility as well as fragility of various organs. Carbohydrate
      sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical
      enzyme for biosynthesis of dermatan sulfate, a side chain of various
      proteoglycans including biglycan that regulates collagen fibrils through their
      interaction. Mutations in CHST14 were found to cause a new form of EDS, named
      musculocontractural type EDS (mcEDS-CHST14). Large subcutaneous hematomas are one
      of the most serious complications accompanied by decreased quality of life and
      potential lethality. In this study, Chst14 gene-deleted mice were expected to be
      an animal model of the vascular abnormalities of mcEDS-CHST14. However, only
      limited numbers of adult mice were generated because of perinatal lethality in
      most Chst14 gene-deleted homozygote (Chst14-/-) mice. Therefore, we investigated
      the placentas of these fetuses. The placentas of Chst14-/- fetuses showed a
      reduced weight, alterations in the vascular structure, and ischemic and/or
      necrotic-like changes. Electron microscopy demonstrated an abnormal structure of
      the basement membrane of capillaries in the placental villus. These findings
      suggest that Chst14 is essential for placental vascular development and perinatal
      survival of fetuses. Furthermore, placentas of Chst14-/- fetuses could be a
      useful model for vascular manifestations in mcEDS-CHST14, such as the large
      subcutaneous hematomas.

PMID- 29206926
TI  - Impact of cleaner fuel use and improved stoves on acute respiratory infections:
      evidence from India.
AB  - Background: The use of cleaner fuel and improved stoves has been promoted as a
      means to lower harmful emissions from solid fuels. However, little is known about
      how exclusive use of cleaner fuels, mixed fuel use and improved stoves influences
      children's health. Methods: We compared the impact of using liquefied petroleum
      gas (LPG) exclusively with mixed fuel use (LPG plus polluting fuels) and with
      exclusive use of polluting fuels on acute respiratory infections (ARI) among 16
      157 children 0-4 years of age from households in the 2012 Indian Human
      Development Survey. Inverse probability weighting (IPW) procedures for multiple
      treatments were used for this evaluation. Results: Children from households using
      LPG had a 5.0% lower probability of reporting ARI relative to exclusive users of
      polluting fuels, with larger effects (10.7%) in rural households. The probability
      of ARI in households using improved stoves and mixed fuel use was also lower in
      rural households, by 2.9% and 2.8%, respectively. The magnitude of effect varied
      across population subgroups, with the highest effects for children living in
      households living in kachha (low quality material) houses households identified
      as poor. Conclusion: Use of LPG and improved stoves lowered the probability of
      ARI among children younger than 5 years.

PMID- 29206927
TI  - Conservation Genetics of Two Highly Endangered and Poorly Known Species of Zamia
      (Zamiaceae: Cycadales) in Colombia.
AB  - Genetic diversity is key in providing the variation needed to face stochastic
      change. Increased habitat loss alters population size and dynamics posing serious
      threats to the conservation of wild species. Colombia has undergone massive
      deforestation over the last century, but harbors extraordinary high species
      diversity of genus Zamia (Cycadales); however, most of the species are under
      threat. In this study, we targeted the largest accessible remaining populations
      of 2 closely related species growing as endemics in the Magdalena Valley region
      of Colombia. We successfully transferred the SSR loci used in previous Zamia
      studies to these species. In total, we amplified 13 microsatellite loci in 3 wild
      populations, aiming at: 1) assessing genetic diversity and 2) understanding if
      the structure found between the 3 populations reflected species and population
      boundaries due to ecological and historical genetic isolation. We found that the
      actual population size does not reflect population genetic diversity with a small
      population (Perales) harboring the highest genetic diversity. In addition, all
      populations are highly structured regardless of species containment, all showing
      signs of genetic isolation. Given the high degree of ecological threat, and the
      inherent biological traits of Cycads, we provide information regarding the
      prioritization of populations for ex situ management.

PMID- 29206929
TI  - The need for appropriate use criteria: the proof of the pudding.

PMID- 29206928
TI  - Confounding by ill health in the observed association between BMI and mortality:
      evidence from the HUNT Study using offspring BMI as an instrument.
AB  - Background: The observational association between mortality and body mass index
      (BMI) is U-shaped, leading to highly publicized suggestions that moderate
      overweight is beneficial to health. However, it is unclear whether elevated
      mortality is caused by low BMI or if the association is confounded, for example
      by concurrent ill health. Methods: Using HUNT, a Norwegian prospective study, 32
      452 mother-offspring and 27 747 father-offspring pairs were followed up to 2009.
      Conventional hazard ratios for parental mortality per standard deviation of BMI
      were estimated using Cox regression adjusted for behavioural and socioeconomic
      factors. To estimate hazard ratios with reduced susceptibility to confounding,
      particularly from concurrent ill health, the BMI of parents' offspring was used
      as an instrumental variable for parents' own BMI. The shape of mortality-BMI
      associations was assessed using cubic splines. Results: There were 18 365
      parental deaths during follow-up. Conventional associations of mortality from all
      causes, cardiovascular disease and cancer with parents' own BMI were
      substantially nonlinear, with elevated mortality at both extremes and minima at
      21-25 kg m-2. Equivalent associations with offspring BMI were positive and there
      was no evidence of elevated parental mortality at low offspring BMI. The linear
      instrumental variable hazard ratio for all-cause mortality per standard deviation
      increase in BMI was 1.18 (95% confidence interval: 1.10, 1.26), compared with
      1.05 (1.03, 1.06) in the conventional analysis. Conclusions: Elevated mortality
      rates at high BMI appear causal, whereas excess mortality at low BMI is likely
      exaggerated by confounding by factors including concurrent ill health.
      Conventional studies probably underestimate the adverse population health
      consequences of overweight.

PMID- 29206930
TI  - Exploring an Ancient Event in Pumpkin, Gourd, and Melon Evolution.

PMID- 29206931
TI  - Scientists Find Evidence Our Best Friends, Dogs, Similarly Adapted to Malaria in
      Africa.

PMID- 29206933
TI  - Scientists Bring New Insights into the Heritability of HIV Infection Severity.

PMID- 29206932
TI  - Novel oral anticoagulants in patients with chronic kidney disease and atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the most frequent arrhythmia in common clinical
      practice and its prevalence is markedly increased among patients with chronic
      kidney disease (CKD). The presence of CKD increases the incidence of AF and vice
      versa. Both AF and CKD increase the risk of stroke or systemic thromboembolism
      and oral anticoagulation is the mainstay for thromboembolic event prevention in
      patients with AF. Novel oral anticoagulants (NOACs) are nowadays often used in
      patients with AF and CKD, but they display a variable degree of renal elimination
      and the risk of accumulation and bleeding increases among patients with CKD in
      particular as kidney disease progresses. While recent data have demonstrated that
      patients with Stage 3 CKD benefit even more from oral anticoagulation therapies
      in comparison with patients with normal renal function, relatively little is
      known about the best choice of anticoagulation in patients with advanced and, in
      particular, end-stage renal disease, as these patients were excluded from all
      pivotal Phase 3 NOACs trials. This review summarizes current knowledge on the
      efficacy and safety of these agents in individuals with CKD and provides CKD
      stage-specific recommendations.

PMID- 29206934
TI  - Enzymatic Functional Assays of Coagulation Using Small Sample Volumes.
AB  - Current laboratory methods for comprehensive thrombophilia status require large
      blood volumes and long turn-around times. We demonstrate the feasibility of
      performing thrombophilia panel testing of enzymatic functional assays on a
      microfluidic cartridge using low sample volume.Functional assays for Antithrombin
      III, Protein C, Factor VIII, and plasminogen were adapted on the digital
      microfluidic platform by developing novel fluorogenic substrates and establishing
      on-cartridge fluorescence (360/460 nm) detection. Cartridge vs. microtiter plate
      results were compared using samples obtained from pediatric patients. Linear
      regression and Bland-Altman plots were used to establish correlations. Results
      were not significantly different when performed on-cartridge compared to
      microtiter plates. Importantly, the sample volume required is significantly lower
      for all on-cartridge compared to microtiter plate assays (25 MUL vs. 2 ml).This
      study demonstrates the feasibility of thrombophilia panel testing with high
      fidelity using small plasma volume. The efficacy of this near-patient technology
      in clinical settings needs further investigation.

PMID- 29206935
TI  - Report of a Myocarditis Outbreak among Pediatric Patients: Human Herpesvirus 7 as
      a Causative Agent?
AB  - Background: The etiology of myocarditis in children has not yet been completely
      elucidated. Objective: Medical records of eight pediatric patients diagnosed with
      acute myocarditis within a 41-day period in a small-town hospital were
      retrospectively analyzed. Methods: We examined antibody titers of adenovirus,
      Epstein-Barr virus, herpes simplex virus, respiratory syncytial virus, varicella
      zoster virus and cytomegalovirus in peripheral blood. We used polymerase chain
      reaction (PCR) amplification to detect genetic sequences from Human herpesvirus
      (HHV) 7, HHV 6, enterovirus, measles or parvovirus in peripheral blood. Results:
      The causative agent was HHV 7 in four patients. HHV 7 sequences were detected
      through PCR in one patient with rapid deterioration. Of four patients with HHV 7,
      two presented with dilated cardiomyopathy. Conclusion: To our knowledge, this is
      the first report to suggest HHV 7 as a causative agent for acute myocarditis. We
      believe HHV 7 should be considered as a possible etiologic pathogen for patients
      with suspected myocarditis.

PMID- 29206936
TI  - Birthweight of singletons born after cleavage-stage or blastocyst transfer in
      fresh and warming cycles.
AB  - STUDY QUESTION: Does extended culture to the blastocyst stage affect singleton
      birthweight after either fresh or vitrified-warmed embryo transfer? SUMMARY
      ANSWER: Singleton birthweight z-scores did not vary significantly after a fresh
      blastocyst transfer, whereas the additional effect of vitrification remains
      inconclusive. WHAT IS KNOWN ALREADY: Observational studies have associated
      extended culture with an increased risk of preterm birth and low birthweight. On
      the contrary, in terms of birthweight and gestational age, singletons born after
      vitrification have been associated with a better perinatal outcome when compared
      to those born following a fresh transfer. STUDY DESIGN, SIZE, DURATION: Our post
      hoc cohort analysis on neonatal outcomes included 447 liveborn singletons was
      derived from a recent retrospective analysis on cumulative live birth rates after
      cleavage-stage and blastocyst transfers. These babies were born following a fresh
      single cleavage-stage transfer (FCT Day 3, n = 113), fresh single blastocyst
      transfer (FBT Day 5, n = 218), vitrified-warmed cleavage-stage transfer (VCT Day
      3, n = 58) or vitrified-warmed blastocyst transfer (VBT Day 5, n = 58).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton birthweight was the primary
      outcome measure. Gestational age and gender of the newborn were accounted for by
      using birthweight z-scores in a multivariable linear regression analysis,
      adjusting for other confounders (maternal age, BMI, parity and smoking
      behaviour). Vanishing twins were excluded from the analysis. MAIN RESULTS AND THE
      ROLE OF CHANCE: A significantly lower z-score was observed after blastocyst
      transfer compared to cleavage-stage transfer in the vitrified-warmed Day 5 group
      (P = 0.013), a difference not observed in the fresh transfer groups (P = 0.32).
      Following multivariable regression analysis [adjusted regression coefficient (95%
      confidence interval)], the FCT and FBT groups showed no significant influence on
      the birthweight z-scores after fresh transfer [-0.19 (-0.44; 0.05)], but the
      transfer of vitrified blastocysts (VBT) was associated with a lower birthweight [
      0.52 (-0.90; -0.15)] compared with the transfer of vitrified cleavage-stage
      embryos (VCT). LIMITATIONS, REASONS FOR CAUTION: The present cohort was
      relatively small, especially in the vitrified-warmed subgroups. Pregnancy
      associated factors possibly influencing birthweight (such as diabetes,
      hypertension, pre-eclampsia) were also not accounted for in the analysis. WIDER
      IMPLICATIONS OF THE FINDINGS: Different ART procedures, including extended
      culture and vitrification, may hold potential safety issues. These results
      require further confirmation in future larger studies. STUDY FUNDING/COMPETING
      INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29206937
TI  - Functional impact of microRNA regulation in models of extreme stress adaptation.
AB  - When confronted with severe environmental stress, some animals are able to
      undergo a substantial reorganization of their cellular environment that enables
      long-term survival. One molecular mechanism of adaptation that has received
      considerable attention in recent years has been the action of reversible
      transcriptome regulation by microRNA. The implementation of new computational and
      high-throughput experimental approaches has started to uncover the vital
      contributions of microRNA towards stress adaptation. Indeed, recent studies have
      suggested that microRNA may have a major regulatory influence over a number of
      cellular processes that are essential to prolonged environmental stress survival.
      To date, a number of studies have highlighted the role of microRNA in the
      regulation of a metabolically depressed state, documenting stress-responsive
      microRNA expression during mammalian hibernation, frog and insect freeze
      tolerance, and turtle and marine snail anoxia tolerance. These studies
      collectively indicate a conserved principle of microRNA stress response across
      phylogeny. As we are on the verge of dissecting the role of microRNA in
      environmental stress adaptation, this review summarizes recent research advances
      and the hallmark expression patterns that facilitate stress survival.

PMID- 29206938
TI  - Misidentification of Acinetobacter baumannii as Alcaligenes faecalis by VITEK 2
      System; Case Report.
AB  - Acinetobacter baumannii (A. baumannii) is widely known as an opportunistic
      bacterial pathogen that causes infection more frequently among immunocompromised
      individuals. Our case demonstrated the limitation of the current VITEK 2 system
      for the idendification of A. baumannii. Four clinical isolates of A. baumannii
      were identified as Alcaligenes faecalis by the VITEK 2 system. Misidentification
      might lead to unnecessary tests and inappropriate treatments. Additional methods
      appear to be helpful for the accurate identification of A. baumannii for clinical
      microbiology laboratories.

PMID- 29206940
TI  - Neurons in the Human Left Amygdala Automatically Encode Subjective Value
      Irrespective of Task.
AB  - The amygdala plays an important role in the computation of internal reward
      signals. In animals it has been shown to enable a stimulus to indicate the
      current value of a reinforcer. However, the exact nature of the current value
      representations in humans remains unknown. Specifically, do neurons of the human
      amygdala represent current value signals only in tasks requiring valuation? We
      recorded from 406 neurons in the amygdala, orbitofrontal cortex, parahippocampal
      cortex, entorhinal cortex, and hippocampus of 6 neurosurgical patients while
      subjects repeatedly viewed 40 different pictures of sweet or salty "junk food"
      items in 2 different tasks. Neural activity during stimulus inspection in a
      valuation task reflected food preferences in the amygdala, orbitofrontal cortex,
      hippocampus, and entorhinal cortex. Notably, only left amygdala activity
      represented these food preferences even in a sweet-salty classification task.
      Valuation signals of the left amygdala thus appear to be stimulus-, not-task
      driven.

PMID- 29206939
TI  - Paradoxical roles of TGF-beta signaling in suppressing and promoting squamous
      cell carcinoma.
AB  - Transforming growth factor beta (TGF-beta) signaling either promotes or inhibits
      tumor formation and/or progression of many cancer types including squamous cell
      carcinoma (SCC). Canonical TGF-beta signaling is mediated by a number of
      downstream proteins including Smad family proteins. Alterations in either TGF
      beta or Smad signaling can impact cancer. For instance, defects in TGF-beta type
      I and type II receptors (TGF-betaRI and TGF-betaRII) and in Smad2/3/4 could
      promote tumor development. Conversely, increased TGF-beta1 and activated TGF
      betaRI and Smad3 have all been shown to have tumor-promoting effects in
      experimental systems of human and mouse SCCs. Among TGF-beta/Smad signaling, only
      TGF-betaRII or Smad4 deletion in mouse epithelium causes spontaneous SCC in the
      mouse model, highlighting the critical roles of TGF-betaRII and Smad4 in tumor
      suppression. Herein, we review the dual roles of the TGF-beta/Smad signaling
      pathway and related mechanisms in SCC, highlighting the potential benefits and
      challenges of TGF-beta/Smad-targeted therapies.

PMID- 29206941
TI  - Factors Associated with Bottle Feeding in Namibia: Findings from Namibia 2013
      Demographic and Health Survey.
AB  - Aim: The aim of this study is to examine the prevalence of bottle feeding (BF)
      among children aged 0-23 months and factors associated with BF in Namibia.
      Methods: Data from Namibia 2013 Demographic Health Survey were used for the
      study. The study covered last-born alive children aged 0-23 months, making up
      1926 mother-baby pairs. Chi-square tests and binary logistic regression were used
      to test for association between BF and related factors. Results: Prevalence of BF
      in Namibia was 35.7%. In the multivariate analysis, the following factors were
      significantly associated with increased risk of BF: working mothers, hospital
      delivery, increasing child age, higher mother's educational status, higher wealth
      quintile and urban residence. Conclusion: To achieve a substantial decrease in
      bottle usage rate in Namibia, breastfeeding promotion programmes should target
      all mothers but especially those at risk of BF highlighted in the study.

PMID- 29206942
TI  - Understanding decision-making in cardiac imaging: determinants of appropriate
      use.
AB  - Aims: Appropriate Use Criteria (AUC) for echocardiography were developed in 2007
      to facilitate decision-making, reduce variability in test utilization, and
      encourage rational use of imaging. However, there is little evidence that the AUC
      have favourably influenced ordering behaviour. This study explores the factors
      that contribute to clinicians requesting echocardiograms with a focus on
      appropriate use. Methods and results: Semi-structured face-to-face interviews
      with cardiologists and non-cardiologists who had requested echocardiograms were
      conducted at an Australian tertiary hospital. The interview guide included
      hypothetical clinical scenarios to better understand decision-making in ordering
      echocardiograms and the actions they could take when receiving test reports.
      Interviews underwent thematic analysis. Seventeen clinicians were interviewed,
      ten of whom were cardiologists. All participants ordered echocardiograms to
      support their clinical decision-making. Awareness of the AUC was low. The
      categorization of tests as 'appropriate' or 'inappropriate' was considered
      ineffective as it failed to reflect the decision-making process. The decision to
      request echocardiograms was influenced by a number of personal and systemic
      factors as well as guidelines and protocols. Training and experience, patients'
      expectations, and management of uncertainty were key personal factors. Systemic
      factors involved the accessibility of services and health insurance status of the
      patient. Conclusion: Factors that influenced the ordering of echocardiograms by
      clinicians at a tertiary care hospital did not appear to be amenable to control
      with AUC. Alternative approaches may be more effective than the AUC in addressing
      the overuse of echocardiography.

PMID- 29206943
TI  - Time to redefine endometriosis including its pro-fibrotic nature.
AB  - Endometriosis is currently defined as presence of endometrial epithelial and
      stromal cells at ectopic sites. This simple and straightforward definition has
      served us well since its original introduction. However, with advances in disease
      knowledge, endometrial stromal and glands have been shown to represent only a
      minor component of endometriotic lesions and they are often absent in some
      disease forms. In rectovaginal nodules, the glandular epithelium is often not
      surrounded by stroma and frequently no epithelium can be identified in the wall
      of ovarian endometriomas. On the other hand, a smooth muscle component and
      fibrosis represent consistent features of all disease forms. Based on these
      observations, we believe that the definition of endometriosis should be
      reconsidered and reworded as 'A fibrotic condition in which endometrial stroma
      and epithelium can be identified'. The main reasons for this change are: (1) to
      foster the evaluation of fibrosis in studies on endometriosis pathogenesis using
      animal models; (2) to limit potential false negative diagnoses if pathologists
      stick stringently to the current definition of endometriosis requiring the
      demonstration of endometrial stromal and glands; (3) to consider fibrosis as a
      potential target for treatment in endometriosis. This opinion article is aimed at
      boosting the attention paid to a largely neglected aspect of the disease. We hope
      that targeting the fibrotic process might increase success in developing new
      therapeutic approaches.

PMID- 29206944
TI  - The direct and indirect effects of kisspeptin-54 on granulosa lutein cell
      function.
AB  - STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the
      expression of genes involved in ovarian reproductive function, steroidogenesis
      and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when
      compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use
      of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes
      involved in ovarian steroidogenesis in human GL cells including, FSH receptor
      (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR),
      aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid
      dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional
      maturation triggers, but did not alter markers of OHSS. WHAT IS KNOWN ALREADY:
      hCG is the most widely used trigger of oocyte maturation, but is associated with
      an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation
      is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a
      novel therapeutic option that safely triggers oocyte maturation even in women at
      high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by
      acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also
      expressed in the human ovary, but there is limited data on the direct action of
      kisspeptin on the ovary. STUDY DESIGN SIZE, DURATION: Forty-eight women
      undergoing IVF treatment for infertility consented to kisspeptin-54 triggering
      and/or granulosa cell collection and were included in the study. Twelve women
      received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger
      oocyte maturation. In the kisspeptin-54 group, 12 received one injection of
      kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a
      10 h interval (9.6 nmol/kg * 2). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Follicular fluid was aspirated and pooled from follicles during the retrieval of
      oocytes for IVF/ICSI. GL cells were isolated and either RNA extracted immediately
      or cultured in vitro +/- kisspeptin or hCG. MAIN RESULTS AND THE ROLE OF CHANCE:
      GL cells from women who had received kisspeptin-54 had a 14-fold and 8-fold
      higher gene expression of FSHR and a 2-fold (ns) and 2.5-fold (P < 0.05) higher
      expression of LHCGR than GL cells from women who had received hCG or GnRH
      agonist, respectively. CYP19A1 expression was 3.6-fold (P < 0.05) and 4.5-fold (P
      < 0.05) higher, STAR expression was 3.4-fold (P < 0.01) and 1.8-fold (P < 0.05)
      higher, HSD3B2 expression was 7.5- (P < 0.01) and 2.5-fold higher (P < 0.05),
      INHBA was 2.5-fold (P < 0.01) and 2.5-fold (P < 0.01) higher in GL cells from
      women who had received kisspeptin-54 than hCG or GnRHa, respectively. ESR1 (P <
      0.05) and ESR2 (P < 0.05) both showed 3-fold higher expression in cells from
      kisspeptin treated than GnRHa treated women. Markers of vascular permeability and
      oocyte growth factors were unchanged (VEGFA, SERPINF1, CDH5, amphiregulin,
      epiregulin). Gene expression of kisspeptin receptor was unchanged. Whereas
      treating GL cells in vitro with hCG induced steroidogenic gene expression,
      kisspeptin-54 had no significant direct effects on either OHSS genes or
      steroidogenic genes. LIMITATIONS REASONS FOR CAUTION: Most women in the study had
      PCOS, which may limit applicability to other patient groups. For the analysis of
      the in vitro effects of kisspeptin-54, it is important to note that GL cells had
      already been exposed in vivo to an alternate maturation trigger. WIDER
      IMPLICATIONS OF THE FINDINGS: The profile of serum gonadotropins seen with
      kisspeptin administration compared to other triggers more closely resemble that
      of the natural cycle as compared with hCG. Thus, kisspeptin could potentially
      permit an ovarian environment augmented for steroidogenesis, in particular
      progesterone synthesis, which is required for embryo implantation. STUDY
      FUNDING/COMPETING INTEREST(S): Dr Owens is supported by an Imperial College
      London PhD Scholarship. Dr Abbara is supported by an National Institute of Health
      Research Academic Clinical Lectureship. The authors do not have any conflict of
      interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01667406.

PMID- 29206945
TI  - Exploring practices and perceptions of alcohol use during pregnancy in England
      and Sweden through a cross-cultural lens.
AB  - Background: Qualitative studies have aimed to understand why some women continue
      to drink during pregnancy; however, there is a lack of comparative cross-cultural
      research. We aimed to explore perceptions and practices of alcohol use during
      pregnancy in England and Sweden. Methods: Semi-structured interviews were
      conducted with 21 parents in Merseyside, England and 22 parents in Orebro County,
      Sweden. Interviews were audio recorded, transcribed verbatim and translated. Data
      were analyzed using thematic analysis. Results: The majority of women in both
      countries abstained from alcohol when they found out they were pregnant, despite
      alcohol being part of many social contexts before pregnancy. Nine of the
      seventeen English women drank at some point during pregnancy, typically on
      special occasions. Most parents felt women should modify their alcohol intake
      when they become mothers, though several English parents argued that responsible
      motherhood did not necessarily equate to abstinence. Swedish parents held strong
      opinions against drinking during pregnancy and argued that any amount of alcohol
      could harm the foetus. English parents' opinions were divided; some were
      skeptical of whether low to moderate drinking was associated with risks.
      Conclusions: Practices and attitudes towards alcohol use during pregnancy and
      views on foetal rights and responsibilities of pregnant women differed in England
      and Sweden. Shared social norms around drinking may be shaped within the policy
      context of pregnancy drinking guidelines, determining whether women consume
      alcohol or not.

PMID- 29206946
TI  - Meaning Reconstruction among Women following Stillbirth: A Loss Fraught with
      Ambiguity and Doubt.
AB  - Stillbirth (SB), death of a fetus in late stages of pregnancy or during birth,
      usually leads to extended and intense grief among women. However, their grief is
      often disenfranchised and they are denied the social right to mourn their loss.
      Constructivist theories recently assuming a central place in bereavement studies
      inform this article, which aims to identify the meaning that women who experience
      SB ascribe to their loss in general and to the lost figure. This tack may offer
      the opportunity to examine the consequences of the discrepancy between personal
      and environmental constructions of this loss on its personal construction and to
      learn about the essence of the loss. Within the domain of qualitative research,
      the current article draws on phenomenology and the research method that has
      emerged from this approach. Specifically, the article focuses on in-depth
      interviews with 10 women who experienced SB. Its findings suggest that for these
      women, the lost figure and the loss in general engender ambiguity both internally
      that is, within the psyche of women themselves-and externally, within the women's
      social environment. Thus, ambiguity, uncertainty, and doubt infused women's
      experience of SB. Implications for theory and practice are discussed.

PMID- 29206947
TI  - Academic Disruption and Substance Use Disorders: University-Based Treatment
      Facilities.

PMID- 29206948
TI  - Leadership, Literacy, and Translational Expertise in Genomics: Challenges and
      Opportunities for Social Work.
AB  - The transdisciplinary field of genomics is revolutionizing conceptualizations of
      health, mental health, family formation, and public policy. Many professions must
      rapidly acquire genomic expertise to maintain state-of-the-art knowledge in their
      practice. Calls for social workers to build genomic capacity come regularly, yet
      social work education has not prepared practitioners to join the genomics
      workforce in providing socially just, ethically informed care to all clients,
      particularly those from vulnerable and marginalized groups. The authors suggest a
      set of action steps for bringing social work skills and practice into the 21st
      century. They propose that good genomic practice entails bringing social work
      values, skills, and behaviors to genomics. With education and training, social
      workers may facilitate socially just dissemination of genomic knowledge and
      services across practice domains. Increased genomic literacy will support the
      profession's mission to address disparities in health, health care access, and
      mortality.

PMID- 29206949
TI  - The Subjective Experiences of Attention-Deficit/Hyperactivity Disorder of Chinese
      Families in Hong Kong: Co-Construction of Meanings in Multiple Family Groups.
AB  - The subjective experiences of Chinese children in Hong Kong with attention
      deficit/hyperactivity disorder (ADHD) are underexplored. This article reports the
      results of a qualitative study that aims to understand the subjective experiences
      of children with ADHD in Hong Kong, taken from among a clinical sample of Chinese
      families with children struggling with ADHD who have participated in cross
      disciplinary research of multiple family groups (MFG). The participating children
      revealed the subjective experiences of their struggle with the disorder in
      response to their parents' concern at a "press conference," one of the MFG
      activities, which underscored the importance of developing a new social work
      model to meet the multiple psychosocial service needs of these families. The
      article concludes with the discussion of the implications for the new model.

PMID- 29206950
TI  - Formal and Informal Neighborhood Social Organization: Which Promotes Better
      Resident Health?
AB  - Neighborhood social organization captures how neighborhood residents differently
      organize to exert social control and enact their vision of their community.
      Whereas structural aspects of neighborhoods have been found to predict the health
      of neighborhood residents, we know less about whether neighborhood social
      characteristics, like social organization, matter for resident health. In their
      study, authors tested whether two types of social organization-formal and
      informal-were more predictive of resident self-rated health in a diverse sample
      of Chicago residents. They used multilevel models with survey weights, ordered
      dependent variables, and multiple imputation. They found that one measure of
      formal social organization, organizational participation, was significantly
      associated with self-rated health even when controlling for other types of social
      organization and individual participation. The article concludes with a
      discussion of the implications for macro social work practice to address social
      determinants of health and improve community health.

PMID- 29206951
TI  - The Effects of Caregiving Resources on Perceived Health among Caregivers.
AB  - This study examined how various types of resources influence perceived health of
      caregivers. Guided by the conservation of resources theory, a caregiver health
      model was built and tested using structural equation modeling. The caregiver
      health model consisted of caregiving situations (functional limitations and
      cognitive impairments of older adults and caregiving time), resources (financial
      resources, mastery, social support, family harmony, and service utilization),
      caregiver burden, and perceived health of caregivers. The sample included 1,837
      unpaid informal caregivers drawn from the 2004 National Long-Term Caregiver
      Survey. The model fit indices indicated that the first structural model did not
      fit well; however, the revised model yielded an excellent model fit. More
      stressful caregiving situations were associated with fewer resources and higher
      burden, whereas greater resources were associated with lower burden and better
      perceived health of caregivers. The results suggest explicit implications for
      social work research and practice on how to protect the health of caregivers.

PMID- 29206952
TI  - Dental Disparities among Low-Income American Adults: A Social Work Perspective.

PMID- 29206953
TI  - Social Workers as Behavioral Health Consultants in the Primary Care Clinic.

PMID- 29206954
TI  - Social Determinants of Health: Grand Challenges in Social Work's Future.

PMID- 29206955
TI  - AIMS: A Care Coordination Model to Improve Patient Health Outcomes.

PMID- 29206956
TI  - Psychological Problems Experienced by Women with Gynecological Cancer and How
      They Cope with It: A Phenomenological Study in Turkey.
AB  - This study was carried out to reveal, in detail, the psychosocial problems faced
      by women in Turkey during their illness with gynecological cancer, and how they
      cope with these problems. The phenomenological approach used for the methodology
      is consistent with that described by Clark Moustakas's transcendental
      phenomenology. The sample included 17 married women. A semistructured, in-depth
      question directive was used to collect the data. The psychological problems found
      in the women in the study included frustration and despair, depression, inability
      to control anger, disruption in body image, and problems with their sex lives.
      The women in the study stated that, among other activities, they prayed
      frequently. They also emphasized that social support from family and others was
      important in coping. The majority said that they were able to cope through
      denial. Women under treatment for gynecological cancer should be evaluated from a
      psychosocial standpoint, and spiritual care and social support should be provided
      as they frequently use these to cope with their illness. It is recommended that a
      team be created, consisting of nurses, psychiatrists or psychologists, and
      religious staff to meet these needs.

PMID- 29206957
TI  - Sleep as an Underused Target for Rapid Response in the Treatment of Depression
      and Suicidal Ideation.

PMID- 29206959
TI  - Identifying Risk for Suicide.

PMID- 29206960
TI  - Spotlight on recently published ICVTS articles.

PMID- 29206958
TI  - The Impact of Racial and Socioeconomic Disparities on Binge Eating and Self
      Efficacy among Adults in a Behavioral Weight Loss Trial.
AB  - The prevalence of obesity is a significant problem among racial and ethnic
      minorities and those of low socioeconomic status (SES). Psychosocial barriers,
      such as binge eating and low self-efficacy, are known to hinder the adoption of a
      more healthful diet. There is limited research identifying racial and SES
      differences in binge eating and self-efficacy. Further investigations of these
      constructs may allow researchers to improve the effectiveness of weight
      management interventions and increase social worker involvement. In this article,
      the authors examine the socioeconomic and racial differences in binge eating and
      eating self-efficacy in a sample of individuals seeking weight loss treatment (N
      = 151). They explore associations between various sociodemographic variables and
      the Binge Eating Scale and Weight Efficacy Lifestyle Questionnaire (WEL). At
      baseline, nonwhite participants or those with fewer years of education exhibited
      more confidence resisting eating when food was available. Moreover, nonwhite
      participants reported more self-confidence eating under social pressure and had
      higher total WEL scores than white participants. However, at six months, nonwhite
      participants' WEL scores decreased. White participants increased their total WEL
      scores and obtained a higher percent weight change by the end of the
      intervention. Additional investigations on the dynamics affecting the development
      of self-efficacy are warranted.

PMID- 29206961
TI  - Corrigendum to '2017 ESC/EACTS Guidelines for the management of valvular heart
      disease' [Eur J Cardiothorac Surg 2017;52:616-664].

PMID- 29206962
TI  - Health promotion, partnership and intersectoral action.

PMID- 29206964
TI  - David Holmes MD FACC.

PMID- 29206963
TI  - Occupational Exposure to Alcohol-Based Hand Sanitizers: The Diagnostic Role of
      Alcohol Biomarkers in Hair.
AB  - Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair are effective
      direct biomarkers of ethanol ingestion, whose analytical determination can be
      used to discriminate between chronic and occasional ethanol intake. Ethanol is a
      compound widely used in some workplaces (e.g., clinics, hospitals) and is present
      in considerable amounts in mouthwash for oral cleaning, medications, cosmetic
      products, hydro-alcoholic disinfectants and antiseptics for hands. This study
      examined the ethyl alcohol exposure derived from hand disinfectants (in gel form)
      by simulating the typical occupational situation of medical-health workers
      (healthcare workers, nurses, surgeons, etc.) who frequently wash their hands with
      antiseptic sanitizer. Two types of hand disinfectants with 62% w/w of ethanol
      content were daily applied to the hands of a teetotaler for 20 times a day, for 4
      consecutive weeks, thus simulating a typical workplace situation and a cumulative
      dermal exposure to ethanol of ~1,100 g. Different matrices (head, chest and beard
      hair, urine) were regularly sampled and analyzed using a ultra high-performance
      liquid chromatography tandem massspectrometry validated method for EtG and a
      (HS)SPME-GC-MS validated technique for FAEEs. The data obtained showed that a
      significant dermal absorption and/or inhalation of ethanol occurred, and that the
      use of detergents produce urinary EtG concentrations both higher than the cut
      offs normally used for clinical and forensic analyses (either 100 and 500 ng/mL,
      depending on the context). The concentrations of the ethanol metabolites in the
      keratin matrices were, respectively, below the cut-off of 7 pg/mg for EtG and
      below 0.5 ng/mg for FAAEs (0.35 ng/mg for ethyl palmitate). In conclusion, the
      regular use of alcohol-based hand sanitizers can affect the concentration of
      urinary EtG and lead to positive analytical results, particularly when specimens
      are obtained shortly after sustained use of ethanol-containing hand sanitizer. On
      the other hand, direct biomarkers of alcohol abuse in the keratin matrix are
      capable of distinguishing between ethanol consumption and incidental exposures.

PMID- 29206965
TI  - Training the next generation of cardiovascular leaders in health policy and
      economics.

PMID- 29206966
TI  - The EuroCTO Club Anniversary meeting.

PMID- 29206967
TI  - Ferrara II.

PMID- 29206968
TI  - New from ESC: ESC Journals Twitter.

PMID- 29206969
TI  - Managing aortic stenosis with TAVI or surgery: risk assessement and long-term
      outcome.

PMID- 29206970
TI  - Thrombospondin-1 and disease progression in dysferlinopathy.
AB  - The purpose of this study was to determine whether thrombospondin (TSP)-1
      promotes macrophage activity and disease progression in dysferlinopathy. First,
      we found that levels of TSP-1 are elevated in blood of non-ambulant
      dysferlinopathy patients compared with ambulant patients and healthy controls,
      supporting the idea that TSP-1 levels are correlated with disease progression. We
      then crossed dysferlinopathic BlaJ mice with TSP-1 knockout mice and assessed
      disease progression longitudinally with magnetic resonance imaging (MRI). In
      these mice, deletion of TSP-1 ameliorated loss in volume and mass of the
      moderately affected gluteal muscle but not of the severely affected psoas muscle.
      T2 MRI parameters revealed that loss of TSP-1 modestly inhibited inflammation
      only in gluteal muscle of male mice. Histological assessment indicated that
      deletion of TSP-1 reduced inflammatory cell infiltration of muscle fibers, but
      only early in disease progression. In addition, flow cytometry analysis revealed
      that, in males, TSP-1 knockout reduced macrophage infiltration and phagocytic
      activity, which is consistent with TSP-1-enhanced phagocytosis and pro
      inflammatory cytokine induction in cultured macrophages. In summary, TSP-1
      appears to play an accessory role in modulating Mp activity in BlaJ mice in a
      gender, age and muscle-dependent manner, but is unlikely a primary driver of
      disease progression of dysferlinopathy.

PMID- 29206971
TI  - An unexpected response to rituximab in a patient with rheumatoid arthritis.

PMID- 29206973
TI  - Social Work Should Be More Proactive in Addressing the Need to Plan for End of
      Life.

PMID- 29206972
TI  - Nutritional Deficiencies and Clinical Correlates in First-Episode Psychosis: A
      Systematic Review and Meta-analysis.
AB  - Objective: Diet is increasingly recognized as a potentially modifiable factor
      influencing the onset and outcomes of psychiatric disorders. Whereas, previous
      research has shown long-term schizophrenia is associated with various nutritional
      deficiencies, this meta-analysis aimed to determine the prevalence and extent of
      nutritional deficits in first-episode psychosis (FEP). Method: A search of
      electronic databases conducted in July 2017 identified 28 eligible studies,
      examining blood levels of 6 vitamins and 10 minerals across 2612 individuals:
      1221 individuals with FEP and 1391 control subjects. Meta-analyses compared
      nutrient levels in FEP to nonpsychiatric controls. Clinical correlates of
      nutritional status in patient samples were systematically reviewed. Results:
      Significantly lower blood levels of folate (N = 6, n = 827, g = -0.624, 95%
      confidence interval [CI] = -1.176 to -0.072, P = .027) and vitamin D (N = 7, n =
      906, g = -1.055, 95% CI = -1.99 to -0.119, P = .027) were found in FEP compared
      to healthy controls. Synthesis of clinical correlates found both folate and
      vitamin D held significant inverse relationships with psychiatric symptoms in
      FEP. There was also limited evidence for serum level reductions of vitamin C (N =
      2, n = 96, g = -2.207, 95% CI = -3.71 to -0.71, P = .004). No differences were
      found for other vitamins or minerals. Conclusions: Deficits in vitamin D and
      folate previously observed in long-term schizophrenia appear to exist from
      illness onset, and are associated with worse symptomology. Further research must
      examine the direction and nature of these relationships (ie, mediator, moderator,
      or marker) with clinical status in FEP. Future trials assessing efficacy of
      nutrient supplementation in FEP samples should consider targeting and stratifying
      for baseline deficiency.

PMID- 29206974
TI  - Experiences with Health Insurance and Health Care in the Context of Welfare
      Reform.
AB  - Studies have shown that in the wake of welfare reform there has been a drop in
      the health insurance coverage and health care utilization of low-income mothers.
      Using data from 20 telephone interviews, this study explored the health insurance
      and health care experiences of current and former welfare participants living in
      Los Angeles County. This study found that half of these women had been uninsured
      at some point. Many of these lapses in health insurance coverage were linked to
      employment transitions and lack of knowledge regarding eligibility for different
      safety net programs. This study also found that satisfaction with access to
      health care was high among the insured respondents; however, barriers to care
      remained for many individuals, including appointment scheduling issues, limited
      scope of health insurance coverage, narrow provider networks, lack of care
      continuity, and perceived low quality of care. Better linkages between social
      programs assisting with health insurance coverage and improved knowledge among
      program clients may reduce health insurance cycling in this group. New rules for
      Medicaid managed care, currently being considered by the Centers for Medicare and
      Medicaid Services, have the potential to improve access to health care and the
      quality of care for these individuals.

PMID- 29206975
TI  - Health-Related Quality of Life of Low-Socioeconomic-Status Populations in Urban
      China.
AB  - Previous researchers had not yet examined the association between socioeconomic
      status (SES) and health-related quality of life (HRQOL) in urban China. The
      present study attempts to assess HRQOL of lower-SES populations in urban China in
      comparison with middle- and high-SES populations, and then to examine the
      mediating role of sense of control between SES and HRQOL. A national
      representative sample of 1,856 participants responded to the HRQOL survey using
      the 12-item Short Form Health Survey (SF-12), conducted by the Chinese General
      Social Survey research team in 2010. The results showed that lower-SES
      populations reported lower HRQOL than middle- and high-SES populations. Sense of
      control could partially mediate the association between social class and HRQOL.
      These findings will generate significant policy and practice implications for
      identifying those at particular risk for lower HRQOL and, accordingly, suggesting
      ways to improve their HRQOL through specific social work interventions in urban
      China's context.

PMID- 29206976
TI  - Talking about Sexuality and Intimacy with Women Spousal Caregivers: Perspectives
      of Service Providers.
AB  - This article reports the findings of an exploratory study examining service
      provider perceptions and experiences of addressing sexuality and intimacy with
      women spousal caregivers. The caregiver-provider encounter is examined, and
      challenges faced by service providers in addressing sexuality are considered.
      Themes identified include ambivalence and discomfort, personal and institutional
      barriers, meanings attributed to sexuality and intimacy, and lack of
      opportunities to discuss experiences. Strategies to overcome silence and
      invisibility on the part of service providers in the health and social services
      system are considered.

PMID- 29206977
TI  - Underuse and Unawareness of Residential Respite Care Services in Dementia
      Caregiving: Constraining the Need for Relief.
AB  - This article describes an analysis of the use of residential respite care
      services and the factors that influence the use of such services among informal
      caregivers of people with dementia. The authors studied a sample of 223
      caregivers participating in a community-based intervention project in northern
      Portugal. Participants provided information on their overall caregiving situation
      and on their use or willingness to use respite care services. Results showed that
      fewer than 6 percent of caregivers accessed the services and that although most
      caregivers were not familiar with these services, they recognized their
      importance and strongly considered the possibility of using them. Part-time care,
      lower levels of gratification, higher burden, and the care receiver's attendance
      of day center supported the willingness to use residential respite services. The
      limited offer, not knowing about the services, and cultural issues related to the
      family duties within the caregiving role can explain the low use of these
      services. Social work professionals have an important role in promoting
      residential respite care services, and thereby helping to reduce caregiving
      overload.

PMID- 29206978
TI  - Analysis of Advance Directive Documentation to Support Palliative Care Activities
      in Nursing Homes.
AB  - As part of an intervention to improve health care in nursing homes with the goal
      of reducing potentially avoidable hospital admissions, 1,877 resident records
      were reviewed for advance directive (AD) documentation. At the initial phases of
      the intervention, 50 percent of the records contained an AD. Of the ADs in the
      resident records, 55 percent designated a durable power of attorney for health
      care, most often a child (62 percent), other relative (14 percent), or spouse (13
      percent). Financial power of attorney documents were sometimes found within the
      AD, even though these documents focused on financial decision making rather than
      health care decision making. Code status was the most prevalent health preference
      documented in the record at 97 percent of the records reviewed. The intervention
      used these initial findings and the philosophical framework of respect for
      autonomy to develop education programs and services on advance care planning. The
      role of the social worker within an interdisciplinary team is discussed.

PMID- 29206979
TI  - Seasonal Difference in National School Lunch Program Participation and Its
      Impacts on Household Food Security.
AB  - The National School Lunch Program (NSLP) is one of the most important food
      assistance programs in the United States to ensure children's food security and
      healthy development. Previous studies have offered mixed results and challenges
      in estimating the effects of program participation. This study assesses NSLP's
      effect on household food security using data from the Survey of Income and
      Program Participation (SIPP). SIPP collects information on food security that
      covers four reference months, including both summer (June, July, August) and
      nonsummer months. The number of summer months in these four reference months
      varies by SIPP rotation group. These unique features allow this study to address
      the potential selection bias in the research of NSLP and food security by
      examining a seasonal difference in program participation. The analysis found that
      one more summer month in the reference period increases the difference in low
      food security rates by about 1.5 percentage points between recipients and
      nonrecipients eligible for free or reduced-price lunch. Findings have important
      social work and health policy implications for increasing food security among low
      income households with children.

PMID- 29206980
TI  - Social Security's Disability Hearings Backlog: A National Crisis.

PMID- 29206981
TI  - Variable Molecular Markers for the Order Mantophasmatodea (Insecta).
AB  - The recently discovered insect order Mantophasmatodea currently comprises 19
      Southern African species. These mainly occur in allopatry, have high levels of
      color polymorphism and communicate via species- and gender-specific vibratory
      signals. High levels of interspecific morphological conservatism mean that
      cryptic species are likely to be uncovered. These aspects of Mantophasmatodean
      biology make them an ideal group in which to investigate population divergence
      due to habitat-specific adaptation, sexual selection, and potentially sensory
      speciation. Lack of appropriate genetic markers has thus far rendered such
      studies unfeasible. To address this need, the first microsatellite loci for this
      order were developed. Fifty polymorphic loci were designed specifically for
      Karoophasma biedouwense (Austrophasmatidae), out of which 23 were labeled and
      tested for amplification across the order using 2-3 individuals from 10 species,
      representing all 4 currently known families. A Bayesian mitochondrially encoded
      cytochrome c oxidase I (COI) topology was reconstructed and divergence dates
      within the order were estimated for the first time. Amplification success and
      levels of polymorphism were compared with genetic divergence and time since
      divergence. In agreement with studies on vertebrate taxa, both amplification and
      variability were negatively correlated with distance (temporal and genetic). The
      high number of informative loci will offer sufficient resolution for both broad
      level population genetic analysis and individual based pedigree or parentage
      analyses for most species in Austrophasmatidae, with at least some loci available
      for the other families. This resource will facilitate research into the
      evolutionary biology of this understudied but fascinating group.

PMID- 29206982
TI  - Measures and metrics of sustainable diets with a focus on milk, yogurt, and dairy
      products.
AB  - The 4 domains of sustainable diets are nutrition, economics, society, and the
      environment. To be sustainable, foods and food patterns need to be nutrient-rich,
      affordable, culturally acceptable, and sparing of natural resources and the
      environment. Each sustainability domain has its own measures and metrics.
      Nutrient density of foods has been assessed through nutrient profiling models,
      such as the Nutrient-Rich Foods family of scores. The Food Affordability Index,
      applied to different food groups, has measured both calories and nutrients per
      penny (kcal/$). Cultural acceptance measures have been based on relative food
      consumption frequencies across population groups. Environmental impact of
      individual foods and composite food patterns has been measured in terms of land,
      water, and energy use. Greenhouse gas emissions assess the carbon footprint of
      agricultural food production, processing, and retail. Based on multiple
      sustainability metrics, milk, yogurt, and other dairy products can be described
      as nutrient-rich, affordable, acceptable, and appealing. The environmental impact
      of dairy farming needs to be weighed against the high nutrient density of milk,
      yogurt, and cheese as compared with some plant-based alternatives.

PMID- 29206983
TI  - Cytogenetic Profiling of Myelomas, Association With Complete Blood Count: Study
      of 180 Patients.
AB  - Objectives: To analyze the most common primary and secondary cytogenetic events
      in myelomas using a probe panel designed in our laboratory, and to associate
      those events with hematological and biochemical findings. Methods: Blood
      specimens from patients diagnosed with myeloma were processed to determine
      complete blood count and levels of albumin, creatinine, and beta-2 microglobulin.
      We evaluated bone-marrow specimens for plasma-cell percentage by light microscopy
      and for cytogenetic abnormalities by fluorescence in situ hybridization (FISH).
      The Mann-Whitney U test was used to compare hematological and biochemical
      parameters. Results: We observed immunoglobulin heavy chain (IgH) gene
      translocations in 43.3% and t(4;14) in 21% of specimens; t(11;14) was observed in
      7.7% of specimens. Gain of chromosomes was observed in 67.2% and loss observed in
      16.6% of specimens. Conclusions: Gains of chromosomes were observed in two-thirds
      of patients with myeloma. The most common IgH translocation was t(4;14);
      del13/monosomy13 was the most common secondary cytogenetic abnormality. Partial
      or complete tetrasomies were associated with higher beta-2 microglobulin levels.

PMID- 29206984
TI  - Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain:
      Consensus Recommendations.
AB  - Objective: To develop consensus recommendations on urine drug monitoring (UDM) in
      patients with chronic pain who are prescribed opioids. Methods: An
      interdisciplinary group of clinicians with expertise in pain, substance use
      disorders, and primary care conducted virtual meetings to review relevant
      literature and existing guidelines and share their clinical experience in UDM
      before reaching consensus recommendations. Results: Definitive (e.g.,
      chromatography-based) testing is recommended as most clinically appropriate for
      UDM because of its accuracy; however, institutional or payer policies may require
      initial use of presumptive testing (i.e., immunoassay). The rational choice of
      substances to analyze for UDM involves considerations that are specific to each
      patient and related to illicit drug availability. Appropriate opioid risk
      stratification is based on patient history (especially psychiatric conditions or
      history of opioid or substance use disorder), prescription drug monitoring
      program data, results from validated risk assessment tools, and previous UDM.
      Urine drug monitoring is suggested to be performed at baseline for most patients
      prescribed opioids for chronic pain and at least annually for those at low risk,
      two or more times per year for those at moderate risk, and three or more times
      per year for those at high risk. Additional UDM should be performed as needed on
      the basis of clinical judgment. Conclusions: Although evidence on the efficacy of
      UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is
      recommended by the panel as part of ongoing comprehensive risk monitoring in
      patients prescribed opioids for chronic pain.

PMID- 29206985
TI  - Advanced Maternal Age and the Risk of Low Birth Weight and Preterm Delivery: a
      Within-Family Analysis Using Finnish Population Registers.
AB  - Advanced maternal age at birth is considered a major risk factor for birth
      outcomes. It is unclear to what extent this association is confounded by maternal
      characteristics. To test whether advanced maternal age at birth independently
      increases the risk of low birth weight (<2,500 g) and preterm birth (<37 weeks'
      gestation), we compared between-family models (children born to different mothers
      at different ages) with within-family models (children born to the same mother at
      different ages). The latter procedure reduces confounding by unobserved parental
      characteristics that are shared by siblings. We used Finnish population
      registers, including 124,098 children born during 1987-2000. When compared with
      maternal ages 25-29 years in between-family models, maternal ages of 35-39 years
      and >=40 years were associated with percentage increases of 1.1 points (95%
      confidence intervals: 0.8, 1.4) and 2.2 points (95% confidence intervals: 1.4,
      2.9), respectively, in the probability of low birth weight. The associations are
      similar for the risk of preterm delivery. In within-family models, the
      relationship between advanced maternal age and low birth weight or preterm birth
      is statistically and substantively negligible. In Finland, advanced maternal age
      is not independently associated with the risk of low birth weight or preterm
      delivery among mothers who have had at least 2 live births.

PMID- 29206986
TI  - Potential for Bias When Estimating Critical Windows for Air Pollution in
      Children's Health.
AB  - Evidence supports an association between maternal exposure to air pollution
      during pregnancy and children's health outcomes. Recent interest has focused on
      identifying critical windows of vulnerability. An analysis based on a distributed
      lag model (DLM) can yield estimates of a critical window that are different from
      those from an analysis that regresses the outcome on each of the 3 trimester
      average exposures (TAEs). Using a simulation study, we assessed bias in estimates
      of critical windows obtained using 3 regression approaches: 1) 3 separate models
      to estimate the association with each of the 3 TAEs; 2) a single model to jointly
      estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We
      used weekly fine-particulate-matter exposure data for 238 births in a birth
      cohort in and around Boston, Massachusetts, and a simulated outcome and time
      varying exposure effect. Estimates using separate models for each TAE were biased
      and identified incorrect windows. This bias arose from seasonal trends in
      particulate matter that induced correlation between TAEs. Including all TAEs in a
      single model reduced bias. DLM produced unbiased estimates and added flexibility
      to identify windows. Analysis of body mass index z score and fat mass in the same
      cohort highlighted inconsistent estimates from the 3 methods.

PMID- 29206987
TI  - Neighborhood Physical Environment and Changes in Body Mass Index: Results From
      the Multi-Ethnic Study of Atherosclerosis.
AB  - Longitudinal associations between neighborhood characteristics and body mass
      index (BMI; weight (kg)/height (m)2) were assessed from 2000 to 2011 among 5,919
      participants in the Multi-Ethnic Study of Atherosclerosis. The perceived
      availability of healthy food and walking environment were assessed via surveys,
      and 1-mile (1.6-km) densities of supermarkets, fruit-and-vegetable stores, and
      recreational facilities were obtained through a commercial database. Econometric
      fixed-effects models were used to estimate the association between within-person
      changes in neighborhood characteristics and within-person change in BMI. In fully
      adjusted models, a 1-standard-deviation increase in the healthy food environment
      index was associated with a 0.16-kg/m2 decrease in BMI (95% confidence interval
      (CI): -0.27, -0.06) among participants with obesity at baseline. A 1-standard
      deviation increase in the physical activity environment index was associated with
      0.13-kg/m2 (95% CI: -0.24, -0.02) and 0.14-kg/m2 (95% CI: -0.27, -0.01) decreases
      in BMI for participants who were overweight and obese at baseline, respectively.
      Paradoxically, increases in the physical activity index were associated with BMI
      increases in persons who were normal-weight at baseline. This study provides
      preliminary longitudinal evidence that favorable changes in neighborhood physical
      environments are related to BMI reductions in obese persons, who comprise a
      substantial proportion of the US population.

PMID- 29206989
TI  - Work-Related Biomechanical Exposure and Job Strain as Separate and Joint
      Predictors of Musculoskeletal Diseases: A 28-Year Prospective Follow-up Study.
AB  - We investigated how work-related biomechanical exposure and job strain in midlife
      separately and jointly predicted back and degenerative musculoskeletal diseases
      (MSDs). A total of 6,257 employees participated in the Finnish Longitudinal Study
      on Aging Municipal Employees (FLAME) in 1981 and were followed up for 28 years.
      Risk ratios and the relative excessive risk due to interaction and 95% confidence
      intervals were modeled for separate and joint prediction estimates, respectively.
      After adjustment for confounders, job strain predicted degenerative MSDs among
      women after 4 and 11 years of follow-up. After 11 years, both exposures predicted
      both types of MSDs among men. Joint exposure predicted both types of MSDs after 4
      years among women (for back MSDs, risk ratio (RR) = 1.58, 95% confidence interval
      (CI): 1.15, 2.18; for degenerative MSDs, RR = 1.59, 95% CI: 1.21, 2.07) and men
      (for back MSDs, RR = 1.50, 95% CI: 1.05, 2.15; for degenerative MSDs, RR = 1.61,
      95% CI: 1.16, 2.22) and both types of MSDs after 11 years (for back MSDs, RR =
      1.72, 95% CI: 1.21, 2.43; for degenerative MSDs, RR = 1.68, 95% CI: 1.25, 2.46)
      among men only, but the relative excessive risk due to interaction was not
      significant throughout. However, after 28 years, the separate and joint exposures
      did not predict MSDs. Workplace interventions should be focused on reducing job
      strain along with biomechanical exposure for possible prevention of MSDs in
      working life and around the time of retirement, but there may be other pathways
      of onset of MSDs in old age.

PMID- 29206988
TI  - Group-Based Trajectory of Body Shape From Ages 5 to 55 Years and Cardiometabolic
      Disease Risk in 2 US Cohorts.
AB  - The association of adiposity across the life span with cardiometabolic risk is
      not completely delineated. We used a group-based modeling approach to identify
      distinct trajectories of body shape from ages 5 years to 55 years among 84,792
      women from the Nurses' Health Study (1976-2010) and 37,706 men from the Health
      Professionals Follow-up Study (1986-2010) and assessed the associations between
      these trajectories and incidence of type 2 diabetes and cardiovascular disease
      (CVD) during a 17-year follow-up period. Compared with those who maintained
      leanness throughout the life span ("lean-stable" trajectory), participants who
      maintained a medium body shape ("medium-stable" trajectory) had somewhat
      increased risk. Those who started lean but had a moderate or marked increase in
      adiposity ("lean-moderate increase" and "lean-marked increase" trajectories) had
      even higher risk (e.g., for a "lean-marked increase" trajectory, the hazard ratio
      for diabetes was 8.11 (95% confidence interval (95% CI): 7.10, 9.27) in women and
      2.36 (95% CI: 2.04, 2.74) in men; for CVD, it was 1.38 (95% CI: 1.25, 1.52) in
      women and 1.28 (95% CI: 1.16, 1.41) in men). Participants who started heavy and
      became heavier (a "heavy-increase" trajectory) had substantially elevated risk
      (for diabetes, the hazard ratio was 7.34 (95% CI: 6.40, 8.42) in women and 2.80
      (95% CI: 2.37, 3.31) in men; for CVD, it was 1.55 (95% CI: 1.40, 1.71) in women
      and 1.35 (95% CI: 1.20, 1.53) in men). Our data showed that trajectories of body
      shape from ages 5 to 55 years were associated with subsequent risk of developing
      type 2 diabetes and CVD.

PMID- 29206990
TI  - Measuring the Impact of Disasters Using Publicly Available Data: Application to
      Hurricane Sandy (2012).
AB  - The unexpected nature of disasters leaves little time or resources for organized
      health surveillance of the affected population, and even less for those who are
      unaffected. An ideal epidemiologic study would monitor both groups equally well,
      but would typically be decided against as infeasible or costly. Exposure and
      health outcome data at the level of the individual can be difficult to obtain.
      Despite these challenges, the health effects of a disaster can be approximated.
      Approaches include 1) the use of publicly available exposure data in geographic
      detail, 2) health outcomes data-collected before, during, and after the event,
      and 3) statistical modeling designed to compare the observed frequency of health
      outcomes with the counterfactual frequency hidden by the disaster itself. We
      applied these strategies to Hurricane Sandy, which struck the northeastern United
      States in October 2012. Hospital admissions data from the state of New York with
      information on primary payer as well as patient demographic characteristics were
      analyzed. To illustrate the method, we present multivariate logistic regression
      results for the first 2 months after the hurricane. Inferential implications of
      admissions data on nearly the entire target population in the wake of a disaster
      are discussed.

PMID- 29206991
TI  - Clinical Predictors of Malaria, Acute Bacterial Meningitis and Treatment Outcomes
      among Febrile Children Admitted with Altered Mental Status in Northwestern
      Tanzania.
AB  - Background: Malaria and acute bacterial meningitis (ABM) are the leading
      infectious causes of febrile encephalopathy in malaria endemic settings. The
      clinical distinction of the two conditions is complicated by overlap in clinical
      features. Objective: To determine the clinical predictors for malaria, ABM and
      treatment outcome in febrile children aged 2 months to 12 years with altered
      mentation at two tertiary hospitals in Northwestern Tanzania. Methods:
      Prospective study of 103 children to document demographic data and physical
      examination findings, such as level of consciousness and meningeal irritations.
      Laboratory results for cerebrospinal fluid, hemoglobin, malaria and HIV were also
      evaluated. Results: Age >60 months and hemoglobin <=5 g/dl were independent
      predictors of malaria; (p = 0.013 and 0.004, respectively). HIV infection was the
      only predictor of meningitis, p = 0.037, and mortality was high if the diagnosis
      was unconfirmed. Conclusions: Children with febrile encephalopathy are more
      likely to have malaria than ABM if they have severe anemia.

PMID- 29206992
TI  - Seroprevalence of lymphatic filariasis among migrant workers in Peninsular
      Malaysia.
AB  - Background: Malaysia aims to eliminate lymphatic filariasis (LF) by the year
      2020, thus the potential threat of LF from migrant workers needs to be
      investigated. Methods: Brugian and bancroftian filariasis among 484 migrant
      workers from six countries were investigated using rapid tests based on detection
      of specific IgG4 antibodies against BmR1 (Brugia Rapid) and BmSXP recombinant
      antigens. Results: The seroprevalence of brugian filariasis was very low;
      however, bancroftian filariasis was notable among workers from India, Nepal and
      Myanmar. Conclusion: Malaysia is not endemic for Wuchereria bancrofti, but
      harbors the vectors for the parasite, thus the results showed that migrant
      workers should be monitored for this infection.

PMID- 29206993
TI  - Longitudinal Relationship Between Knee Pain Status and Incident Frailty: Data
      from the Osteoarthritis Initiative.
AB  - Objective: Examine the longitudinal association between knee pain and
      prefrailty/frailty. Design: Longitudinal study. Setting: Five clinical centers
      across the United States. Subject: Data from 3,053 nonfrail participants aged 45
      79 years at baseline from the Osteoarthritis Initiative. Methods: According to
      self-reported knee pain at baseline, the participants were placed into three
      groups: no knee pain (N = 1,600), unilateral knee pain (N = 822), and bilateral
      knee pain (N = 631). Frailty status was assessed over time using the five frailty
      indicators (unintentional weight loss, exhaustion, weak energy, slow gait speed,
      and little physical activity). Based on the number of frailty indicators present,
      prefrailty (1-2) and frailty (>=3) were diagnosed. Generalized estimating
      equations logistic regression analyses were conducted to examine the relationship
      between knee pain status and prefrailty/frailty. Results: After adjusting for
      age, sex, race, education, marital status, smoking status, comorbidities, and
      body mass index, unilateral knee pain at baseline was associated with an
      increased odds of developing prefrailty (odds ratio [OR] = 1.14, 95% confidence
      interval [CI] = 1.01-1.27) and frailty (OR = 1.89, 95% CI = 1.38-2.62), and
      bilateral knee pain at baseline was also associated with an increased risk of
      prefrailty (OR = 1.41, 95% CI = 1.24-1.62) and frailty (OR = 2.21, 95% CI = 1.63
      3.01) over time in comparison with no knee pain. The interaction of knee pain
      status by time was not significantly associated with either prefrailty or
      frailty. Conclusions: Knee pain (particularly bilateral knee pain) is associated
      with an increased risk of developing prefrailty and frailty over time.

PMID- 29206994
TI  - Trends and patterns in leprosy in nine states of the Republic of the Sudan 7
      years after the introduction of routine contact screening.
AB  - Background: This paper analyzes the trends of key indicators reflecting the
      epidemiological situation of leprosy in nine different states of the Republic of
      the Sudan after the introduction of a systematic contact screening in 2010.
      Methods: The routinely assessed data from the leprosy control program from 2010
      to 2016 were analyzed. Results: Despite, intense contact screening, the overall
      number of new cases detected showed a decreasing trend. The female:male ratio
      among new cases was constantly low. The overall average number of contacts needed
      to screen in order to detect a new case among contacts was 64. However, this
      number varied significantly in the nine states under investigation, with the best
      yield being observed in the state with the lowest case detection rate.
      Conclusions: The total number of new cases of leprosy in nine states of the
      Republic of the Sudan has shown declining tendencies since 2010. Our data are not
      suggestive of a significant impact of contact screening on the trends of leprosy
      key indicators. Overall, contact screening proved to be efficient in most states,
      including those that exhibited very low annual new case detection rates (ANCDRs).
      Sensitization of personnel undergoing training and measures improving access of
      females to leprosy services are urgently needed.

PMID- 29206995
TI  - Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in
      Prostate Cancer.
AB  - Background: Real-time knowledge of the somatic genome can influence management of
      patients with metastatic castration-resistant prostate cancer (mCRPC). While
      routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating
      tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor
      genome. However, no systematic comparisons of matched "liquid" and "solid"
      biopsies have been performed that would enable ctDNA profiling to replace the
      need for direct tissue sampling. Methods: We performed targeted sequencing across
      72 clinically relevant genes in 45 plasma cell-free DNA (cfDNA) samples collected
      at time of metastatic tissue biopsy. We compared ctDNA alterations with exome
      sequencing data generated from matched tissue and quantified the concordance of
      mutations and copy number alterations using the Fisher exact test and Pearson
      correlations. Results: Seventy-five point six percent of cfDNA samples had a
      ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic
      mutations identified in matched metastatic tissue biopsies were concurrently
      present in ctDNA. Furthermore, the hierarchy of variant allele fractions for
      shared mutations was remarkably similar between ctDNA and tissue. Copy number
      profiles between matched liquid and solid biopsy were highly correlated, and
      individual copy number calls in clinically actionable genes were 88.9%
      concordant. Detected alterations included AR amplifications in 22 (64.7%)
      samples, SPOP mutations in three (8.8%) samples, and inactivating alterations in
      tumor suppressors TP53 , PTEN , RB1 , APC , CDKN1B , BRCA2 , and PIK3R1 . In
      several patients, ctDNA sequencing revealed robust changes not present in paired
      solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K
      pathways. Conclusions: Our study shows that, in the majority of patients, a ctDNA
      assay is sufficient to identify all driver DNA alterations present in matched
      metastatic tissue and supports development of DNA biomarkers to guide mCRPC
      patient management based on ctDNA alone.

PMID- 29206996
TI  - Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic
      Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer.
AB  - Background: We investigated tumor regression grading (TRG) as a prognostic marker
      and individual-level surrogate for disease-free survival (DFS) in patients with
      rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur
      Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft
      Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial. Methods: TRG was
      recorded prospectively using the Dworak classification in 1179 patients after
      preoperative fluorouracil-based chemoradiotherapy (CRT) with or without
      oxaliplatin. Multivariable analysis was performed using Cox regression models
      adjusted for treatment arm, resection status, and pathologic stage. Individual
      level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1
      4). All statistical tests were two-sided. Results: With a median follow-up of 50
      months, the addition of oxaliplatin to fluorouracil-based CRT led to
      statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to
      79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more
      advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone.
      The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to
      80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 +
      3 (intermediate regression), and TRG 4 (complete regression), respectively ( P <
      .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3
      vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to
      multicollinearity, TRG 4 and pathologic stage could not be tested within the same
      model. The treatment effect on DFS was captured by TRG, satisfying individual
      level PC4. Conclusions: Higher TRG after preoperative CRT predicted a favorable
      long-term outcome. At the individual patient level, TRG was a surrogate marker
      for DFS. Further phase III trials are needed to validate TRG as a surrogate at
      trial level.

PMID- 29206997
TI  - Healthcare use among immigrants and natives in Sweden on disability pension,
      before and after changes of regulations.
AB  - Background: There is limited knowledge regarding psychiatric healthcare
      utilization around the time of granting disability pension (DP) due to common
      mental disorders (CMD) among immigrants and if this is related to social
      insurance regulations. The aim was to evaluate patterns of psychiatric healthcare
      utilization before and after DP due to CMD among immigrants and natives. A second
      aim was to evaluate if such patterns differed before and after changes in social
      insurance regulations in Sweden in 2008. Methods: All 28 354 individuals living
      in Sweden with incident DP due to CMD, before (2005-06; n = 24 298) or after
      (2009-10; n = 4056) changes in regulations of granting DP, were included.
      Patterns of psychiatric in- and specialized outpatient healthcare utilization
      during a 7-year window around DP granting were assessed by Generalized Estimating
      Equations estimating multivariate adjusted odds ratios (OR) and 95% confidence
      intervals (CI). Results: Prevalence rates of psychiatric inpatient care were
      comparable among immigrants and natives, lower in non-Western immigrants (Africa,
      Asia and South-America). Three years after DP, non-Western immigrants in
      comparison to natives and Western immigrants had a stronger decrease in inpatient
      psychiatric healthcare: OR 0.48 (CI 0.38-0.62), 0.76 (0.70-0.83) and 1.01 (0.76
      1.34), respectively. After 2008, a strong reduction in outpatient psychiatric
      healthcare after DP granting was observed, similarly in immigrants and natives.
      Conclusions: Non-Western immigrants showed a different pattern of inpatient
      specialized healthcare after DP granting in comparison to natives. After changes
      in social insurance regulations, the decline in outpatient psychiatric healthcare
      following DP granting was comparable in immigrants and natives.

PMID- 29206999
TI  - Expansion of Viral Load Testing and the Potential Impact on HIV Drug Resistance.
AB  - The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive
      scale-up of antiretroviral therapy (ART) in high-burden countries and across all
      genders and populations at risk toward global human immunodeficiency virus (HIV)
      epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a
      consequence of aggressive ART scale-up and is actively promoting 3 key steps to
      mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring
      in all settings; (2) optimization of ART regimens; and (3) routine collection and
      analysis of HIVDR data to monitor the success of mitigation strategies. The
      transition to dolutegravir-based regimens in PEPFAR-supported countries and the
      continuous evolution of HIVDR surveillance strategies are essential elements of
      PEPFAR implementation.

PMID- 29207000
TI  - Key Factors Influencing the Emergence of Human Immunodeficiency Virus Drug
      Resistance in Low- and Middle-Income Countries.
AB  - The emergence and spread of human immunodeficiency virus (HIV) drug resistance
      from antiretroviral roll-out programs remain a threat to long-term control of the
      HIV-AIDS epidemic in low- and middle-income countries (LMICs). The patterns of
      drug resistance and factors driving emergence of resistance are complex and
      multifactorial. The key drivers of drug resistance in LMICs are reviewed here,
      and recommendations are made to limit their influence on antiretroviral therapy
      efficacy.

PMID- 29207001
TI  - The Role of HIV-1 Drug-Resistant Minority Variants in Treatment Failure.
AB  - Human immunodeficiency virus type 1 (HIV-1) drug resistance genotyping is
      recommended to help in the selection of antiretroviral therapy and to prevent
      virologic failure. There are several ultrasensitive assays able to detect HIV-1
      drug-resistance minority variants (DRMVs) not detectable by standard population
      sequencing-based HIV genotyping assays. Presence of these DRMVs has been shown to
      be clinically relevant, but its impact does not appear to be uniform across drug
      classes. In this review, we summarize key evidence for the clinical impact of
      DRMVs across drug classes for both antiretroviral treatment-naive and
      antiretroviral treatment-experienced patients, and highlight areas where more
      supporting evidence is needed.

PMID- 29207003
TI  - Risk factors for symptomatic esophageal stricture after caustic ingestion-a
      retrospective cohort study.
AB  - Esophageal stricture is a major secondary complication of ingesting caustic
      agents. We examined our experiences with caustic injuries with a view to finding
      clinical and biological risk factors of esophageal strictures secondary to
      caustic ingestion. Records were retrieved for 58 adults admitted consecutively to
      our intensive care unit for caustic ingestion. Fifty cases were managed
      conservatively and therefore retained for analyses. Patients were grouped
      according to whether they developed strictures or not during the follow-up
      period. Mucosal damage was assessed by emergency endoscopy. Eleven patients (22%)
      developed a stricture. At referral, dysphagia, epigastric pain, and hematemesis
      were associated with secondary stricture (respectively P = 0.047, P = 0.008, P =
      0.02). A high Zargar endoscopic grade (above IIa; P = 0.02), the ingestion of
      strong acids or alkalis (P = 0.006), hyperleukocytosis (P = 0.02), and a low
      prothrombin ratio (P = 0.002) were associated with a higher risk of developing a
      stricture. The median delay of stricture diagnosis was 12 (8;16) days after
      ingestion, with extreme values from 4 to 26 days. Initial symptoms such as
      dysphagia or hematemesis, early endoscopy showing >IIa grade esophagitis, and
      certain laboratory results should draw the physician's attention to a high risk
      of esophageal stricture.

PMID- 29207004
TI  - Phenotypic antimicrobial susceptibility testing of Chlamydia trachomatis isolates
      from patients with persistent or successfully treated infections.
AB  - Objectives: Antimicrobial susceptibility data for Chlamydia trachomatis are
      lacking. Methodologies for susceptibility testing in C. trachomatis are not well
      defined, standardized or performed routinely owing to its intracellular growth
      requirements. We sought to develop an assay for the in vitro susceptibility
      testing of C. trachomatis isolates from two patient cohorts with different
      clinical outcomes. Methods: Twenty-four clinical isolates (11 from persistently
      infected and 13 from successfully treated patients) were overlaid with media
      containing two-fold serial dilutions of azithromycin or doxycycline. After
      incubation, aliquots were removed from the stock inoculum (SI) and each
      antimicrobial concentration for total RNA extraction, complementary DNA
      generation and real-time PCR. The MIC was defined as the lowest antimicrobial
      concentration where a 95% reduction in transcription was evident in comparison
      with the SI for each isolate. Results: MICs of azithromycin were comparable for
      isolates from the two patient groups (82% <= 0.25 mg/L for persistently infected
      and 100% <= 0.25 mg/L for successfully treated patients). Doxycycline MICs were
      at least two-fold lower for isolates from the successfully treated patients
      (53.9% <= 0.064 mg/L) than for the persistently infected patients (100% >= 0.125
      mg/L) (P = 0.006, Fisher's exact test). Overall, 96% of isolates gave
      reproducible MICs when re-tested. Conclusions: A reproducible assay was developed
      for antimicrobial susceptibility testing of C. trachomatis. MICs of azithromycin
      were generally comparable for the two different patient groups. MICs of
      doxycycline were significantly higher in the persistently infected patients.
      However, interpretation of elevated MICs in C. trachomatis is extremely
      challenging in the absence of breakpoints, or wild-type and treatment failure MIC
      distribution data.

PMID- 29207005
TI  - Global Health Journal Club: Is Honey Effective as a Treatment for Chemotherapy
      induced Mucositis in Paediatric Oncology Patients?
AB  - Oral mucositis (OM) is an inflammatory response of mucosal epithelium to the
      cytotoxic effects of chemotherapy and radiotherapy causing severe oral pain and
      ulceration, which may complicate the management of cancer. The Mucositis
      Prevention Guideline Development Group has developed an international guideline
      for the prevention of mucositis in children receiving treatment for cancer or
      undergoing haematopoietic stem cell transplantation. Evidence-based preventative
      strategies include cryotherapy, low-level light therapy and keratinocyte growth
      factor. However, these strategies are often not available in resource-poor
      settings. There is some evidence that honey may be a suitable treatment for OM in
      adult patients. We performed a literature search of 11 databases to find papers
      exploring the use of honey to treat chemotherapy-associated mucositis in
      paediatric oncology patients. We found four papers, which provide Grade C
      evidence that honey is effective as a preventative and therapeutic measure for OM
      in paediatric oncology patients.

PMID- 29207002
TI  - Disability, fatigue, pain and their associates in early diffuse cutaneous
      systemic sclerosis: the European Scleroderma Observational Study.
AB  - Objectives: Our aim was to describe the burden of early dcSSc in terms of
      disability, fatigue and pain in the European Scleroderma Observational Study
      cohort, and to explore associated clinical features. Methods: Patients completed
      questionnaires at study entry, 12 and 24 months, including the HAQ disability
      index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment
      of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates
      examined included the modified Rodnan skin score (mRSS), current digital ulcers
      and internal organ involvement. Correlations between 12-month changes were also
      examined. Results: The 326 patients recruited (median disease duration 11.9
      months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with
      'grip' and 'activity' being most affected. Of the 18 activities assessed in the
      CHFS, those involving fine finger movements were most affected. High HAQ-DI and
      CHFS scores were both associated with high mRSS (rho = 0.34, P < 0.0001 and rho =
      0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital
      ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and
      muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional
      Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated,
      in particular the HAQ-DI with the CHFS (rho = 0.84, P < 0.0001). Worsening HAQ-DI
      over 12 months was strongly associated with increasing mRSS (rho = 0.40, P <
      0.0001), decreasing hand function (rho = 0.57, P < 0.0001) and increasing fatigue
      (rho = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational
      Study highlights the burden of disability in early dcSSc, with high levels of
      disability and fatigue, associating with the degree of skin thickening (mRSS).
      Impaired hand function is a major contributor to overall disability.

PMID- 29207006
TI  - Distal Functional Connectivity of Known and Emerging Cortical Targets for
      Therapeutic Noninvasive Stimulation.
AB  - Noninvasive stimulation is an emerging modality for the treatment of psychiatric
      disorders, including addiction. A crucial element in effective cortical target
      selection is its distal influence. We approached this question by examining
      resting-state functional connectivity patterns in known and potential stimulation
      targets in 145 healthy adults. We compared connectivity patterns with distant
      regions of particular relevance in the development and maintenance of addiction.
      We used stringent Bonferroni-correction for multiple comparisons. We show how the
      anterior insula, dorsal anterior cingulate, and ventromedial prefrontal cortex
      had opposing functional connectivity with striatum compared to the dorsomedial
      prefrontal cortex. However, the dorsolateral prefrontal cortex, the currently
      preferred target, and the presupplementary motor area had strongest negative
      connections to amygdala and hippocampus. Our findings highlight differential and
      opposing influences as a function of cortical site, underscoring the relevance of
      careful cortical target selection dependent on the desired effect on subcortical
      structures. We show the relevance of dorsal anterior cingulate and ventromedial
      prefrontal cortex as emerging cortical targets, and further emphasize the
      anterior insula as a potential promising target in addiction treatment, given its
      strong connections to ventral striatum, putamen, and substantia nigra.

PMID- 29207007
TI  - Fertility preservation in women harboring deleterious BRCA mutations: ready for
      prime time?
AB  - Fertility issues have become critical in the management and counseling of BRCA
      mutation carriers. In this setting four points deserve consideration. (1) Women
      in general lose their ability to conceive at a mean age of 41 years, thus the
      suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for
      BRCA mutation carriers does not affect the chances of natural pregnancy.
      Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation
      prior to surgery should be considered. (2) Some evidence suggests that ovarian
      reserve may actually be partly reduced in BRCA mutations carriers and that the
      mutation may affect ovarian responsiveness to stimulation. However, these
      findings are still controversial. (3) Breast cancer is not rare before the age of
      40 and fertility preservation after diagnosis can be requested in a significant
      proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation
      in young healthy carriers deserves consideration. The procedure could be
      considered at a young age and in an elective setting, when ovarian stimulation
      may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis
      (PGD) could be considered in BRCA mutations carriers, particularly when good
      quality oocytes have been stored at a young age. Based on the current knowledge,
      a univocal approach cannot be recommended; in depth patient counseling is
      warranted.

PMID- 29207008
TI  - Cannabis Use and Hypomania in Young People: A Prospective Analysis.
AB  - Background: Cannabis use in young people is common and associated with
      psychiatric disorders. However, the prospective link between cannabis use and
      bipolar disorder symptoms has rarely been investigated. The study hypothesis was
      that adolescent cannabis use is associated with hypomania in early adulthood via
      several potential etiological pathways. Methods: Data were used from the Avon
      Longitudinal Study of Parents and Children, a UK birth cohort study. The
      prospective link between cannabis use at age 17 and hypomania at age 22-23 years
      was tested using regression analysis, adjusted for gender, early environmental
      risk factors, alcohol and drug use, and depression and psychotic symptoms at age
      18 years. Path analysis examined direct and indirect effects of the link and
      whether gender, childhood family adversity, or childhood abuse are associated
      with hypomania via an increased risk of cannabis use. Results: Data were
      available on 3370 participants. Cannabis use at least 2-3 times weekly was
      associated with later hypomania (OR = 2.21, 95% CI = 1.49-3.28) after adjustment.
      There was a dose-response relationship (any use vs weekly). Cannabis use mediated
      the association of both childhood sexual abuse and hypomania, and male gender and
      hypomania. The cannabis use-hypomania link was not mediated by depression or
      psychotic symptoms. Conclusions: Adolescent cannabis use may be an independent
      risk factor for future hypomania, and the nature of the association suggests a
      potential causal link. Cannabis use mediates the link between childhood abuse and
      future hypomania. As such it might be a useful target for indicated prevention of
      hypomania.

PMID- 29207009
TI  - TAT-fused IP3R-derived peptide enhances cisplatin sensitivity of ovarian cancer
      cells by increasing ER Ca2+ release.
AB  - Ovarian cancer is the most common gynecological malignancy. At present, cisplatin
      is used to treat ovarian cancer; however, the development of cisplatin resistance
      during therapy is a common obstacle to achieving favorable outcomes. Recently,
      the B-cell lymphoma 2 (Bcl-2) BH4 domain has been reported to mediate the
      prosurvival activity of Bcl-2 in cancer; however, the involvement of the BH4
      domain of Bcl-2 in the cisplatin resistance of ovarian carcinoma cells is not
      entirely clear. In this study, we observed the cytoplasmic and mitochondrial
      levels of Ca2+ by confocal laser microscopy. We also detected cell apoptosis
      using western blot analysis and flow cytometry. The present study demonstrated
      that TAT-fused inositol 1,4,5-trisphosphate receptor-derived peptide (TAT-IDPS),
      which targets the BH4 domain of Bcl-2, increased cisplatin-induced Ca2+ flux from
      the endoplasmic reticulum (ER) into the cytosol and mitochondria. In addition,
      TAT-IDPS increased cisplatin-induced expression of mitochondrial apoptosis
      associated proteins and ER stress-associated proteins. These results indicated
      that TAT-IDPS may enhance the cytotoxicity of cisplatin toward ovarian carcinoma
      cells by increasing ER Ca2+ release.

PMID- 29207010
TI  - The potential inhibitory effects of miR-19b on vulnerable plaque formation via
      the suppression of STAT3 transcriptional activity.
AB  - Atherosclerotic plaque growth requires angiogenesis, and acute coronary syndrome
      (ACS) is usually triggered by the rupture of unstable atherosclerotic plaques.
      Previous studies have identified typically circulating microRNA (miRNA/miR)
      profiles in patients with ACS. miRNAs serve important roles in the
      pathophysiology of atherosclerotic plaque progression. The present study aimed to
      investigate the potential role and mechanism of miR-19b in plaque stability.
      miRNA array data indicated that 28 miRNAs were differentially expressed in the
      plasma of patients with unstable angina (UA; n=12) compared with in control
      individuals (n=12), and miR-19b exhibited the most marked upregulation.
      Circulating miR-19b levels were further validated in another independent cohort,
      which consisted of 34 patients with UA and 24 controls, by quantitative
      polymerase chain reaction. Gene Ontology annotations of the predicted target
      genes of miR-19b suggested that miR-19b may be involved in endothelial cell (EC)
      proliferation, migration and angiogenesis, which was confirmed by Cell Counting
      kit-8, wound healing and tube formation assays in the present study. Finally, the
      present study indicated that miR-19b may suppress signal transducer and activator
      of transcription 3 (STAT3) tyrosine phosphorylation and transcriptional activity
      in ECs, as determined by western blot analysis and luciferase reporter assay. In
      conclusion, the present study revealed that increased miR-19b expression may
      delay unstable plaque progression in patients with UA by inhibiting EC
      proliferation, migration and angiogenesis via the suppression of STAT3
      transcriptional activity.

PMID- 29207011
TI  - Astragaloside IV prevents kidney injury caused by iatrogenic hyperinsulinemia in
      a streptozotocin-induced diabetic rat model.
AB  - Diabetic patients are able to manage their blood glucose with exogenous insulin
      but, ultimately, remain at risk of diabetic nephropathy (DN). Long-term use of
      insulin may lead to iatrogenic hyperinsulinemia, which has been suggested to
      cause kidney injury. However, there are no effective interventions for iatrogenic
      hyperinsulinemia leading to kidney damage. In the present paper, the hypothesis
      that astragaloside IV (AS-IV), a novel saponin purified from Astragalus
      membranaceus (Fisch) Bunge, may prevent DN in iatrogenic hyperinsulinemic
      diabetic rats through antioxidative and anti-inflammatory mechanisms was
      investigated. Diabetes was induced with streptozotocin (STZ) (55 mg/kg) by
      intraperitoneal injection in rats. At 1 week following STZ injection, the
      diabetic rats were treated with Levemir subcutaneously for 4 weeks. Diabetic rat
      insulin levels >30 uU/ml were considered as iatrogenic hyperinsulinemia. Rats
      were divided into six groups (n=8 per group): Iatrogenic hyperinsulinemic rats,
      and iatrogenic hyperinsulinemic rats treated with Tempol and AS-IV at 2.5, 5 and
      10 mg/kg/day, intragastric infusion, for 12 weeks. The normal rats were used as a
      non-diabetic control group. AS-IV ameliorated albuminuria, mesangial cell
      proliferation, basement membrane thickening and podocyte foot process effacement
      in iatrogenic hyperinsulinemic rats. In iatrogenic hyperinsulinemic rat renal
      tissues, malondialdehyde, interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), type IV collagen and laminin levels were increased, whereas
      glutathione peroxidase and superoxide dismutase activity levels were decreased.
      Nicotinamide adenine dinucleotide phosphate oxidase 4 expression and
      extracellular signal-regulated kinase 1/2 (ERK1/2) activation were upregulated,
      and canonical transient receptor potential cation channel 6 (TRPC6) protein
      expression was downregulated. However, all these abnormalities were attenuated by
      AS-IV. These findings suggested that AS-IV prevented rat kidney injury caused by
      iatrogenic hyperinsulinemia by inhibiting oxidative stress, IL-1beta and TNF
      alpha overproduction, downregulating ERK1/2 activation, and upregulating TRPC6
      expression.

PMID- 29207012
TI  - MicroRNA-30a-5p suppresses tumor cell proliferation of human renal cancer via the
      MTDH/PTEN/AKT pathway.
AB  - The present study aimed to explore the effects of microRNA (miRNA)-30a-5p on
      tumor proliferation and to seek a potential therapeutic target for the treatment
      of human renal cancer. The results demonstrated that the expression levels of
      miRNA-30a-5p were reduced in tumor samples from patients with renal cancer
      compared with in normal tissue samples. Overall survival and disease-free
      survival were increased in patients with renal cancer and high miRNA-30a-5p
      expression compared with in those with low miRNA-30a-5p. Furthermore,
      overexpression of miRNA-30a-5p suppressed cell proliferation, induced apoptosis,
      and promoted caspase-3/9 activities and B-cell lymphoma 2-associated X protein
      (Bax) protein expression in Caki-2 cells. In addition, the results confirmed that
      overexpression of miRNA-30a-5p inhibited metadherin (MTDH), upregulated
      phosphatase and tensin homolog (PTEN) and suppressed phosphorylated (p)-protein
      kinase B (AKT) protein expression levels in Caki-2 cells. Furthermore,
      transfection with small interfering RNA-MTDH, increased the effects of miRNA-30a
      5p on the inhibition of cell proliferation, and promotion of apoptosis, caspase
      3/9 activities and Bax protein expression levels in Caki-2 cells. Knockdown of
      MTDH expression also upregulated PTEN and suppressed p-AKT protein expression in
      Caki-2 cells. In conclusion, the present study is the first, to the best of our
      knowledge, to provide evidence suggesting that miRNA-30a-5p suppresses tumor
      human renal cancer cell proliferation via the MTDH/PTEN/AKT pathway.

PMID- 29207013
TI  - Effects of kartogenin on the attenuated nucleus pulposus cell degeneration of
      intervertebral discs induced by interleukin-1beta and tumor necrosis factor
      alpha.
AB  - Cytokines are the main cause of intervertebral disc degeneration. Kartogenin
      (KGN) is found to protect chondrocytes from cytokines. To explore whether KGN can
      slow down the degeneration on intervertebral discs following exposure to
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), the
      expression of type II collagen (Col II) and aggrecan were detected by
      immunofluorescence, immunohistochemistry and tissue staining. An in vitro model
      of disc degeneration using human nucleus pulposus cells (hNPCs) and ex vivo
      culture of mouse intervertebral discs organs under the actions of inflammatory
      cytokines were used, and the expression of Col II and aggrecan in hNPCs were
      detected by semi-quantitative western blot analysis, and the mRNA expression of
      the genes than encode Col II and aggrecan were detected by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). The results indicated that the
      expression of Col II and aggrecan was reduced in the degeneration models.
      However, the protein expressions of Col II and aggrecan were significantly
      elevated in hNPCs and the mouse intervertebral discs following addition of KGN.
      RT-qPCR results revealed that the mRNA expression of Col II and aggrecan was
      increased in hNPCs and mouse intervertebral discs following treatment with KGN.
      Thus, KGN effectively increased the expression of Col II and aggrecan in hNPCs
      and slowed the degeneration of intervertebral discs stimulated by IL-1beta and
      TNF-alpha.

PMID- 29207014
TI  - Necroptosis: A novel manner of cell death, associated with stroke (Review).
AB  - Cell death is indispensable in the physiology, pathology, growth, development,
      senility and death of an organism. In recent years, the identification of a
      highly regulated form of necrosis, known as necroptosis, has challenged the
      traditional concept of necrosis and apoptosis, which are two major modes of cell
      death. This novel manner of cell death is similar in form to necrosis in terms of
      morphological features, and it can also be regulated in a caspase-independent
      manner. Therefore, necroptosis can be understood initially as a combination of
      necrosis and apoptosis. The mechanism of its regulation, induction and inhibition
      is complicated, and involves a range of molecular expression and regulation.
      According to the recent literature, necroptosis takes place in the physiological
      regulatory processes of an organism and is involved in the occurrence,
      development and prognosis of a variety of diseases that have a necrosis
      phenotype, including neurodegenerative diseases, ischemic disease, hemorrhagic
      disease, inflammation and viral infectious diseases. In the present review, the
      features, molecular mechanism and identification of necroptosis under
      pathological conditions are discussed, with particular emphasis on its
      association with stroke.

PMID- 29207015
TI  - Human amniotic epithelial cells regulate osteoblast differentiation through the
      secretion of TGFbeta1 and microRNA-34a-5p.
AB  - Since the beginning of the use of stem cells in tissue regenerative medicine,
      there has been a search for optimal sources of stem cells. Human amniotic
      epithelial cells (hAECs) are derived from human amnions, which are typically
      discarded as medical waste, but were recently found to include cells with
      trilineage differentiation potential in vitro. Previous study has focused on the
      osteogenic differentiation ability of hAECs as seed cells in bone regeneration;
      however, their paracrine effects on osteoblasts (OBs) are yet to be elucidated.
      In the present study, conditioned medium (CM) derived from hAECs was used to
      determine their paracrine effects on the human fetal OB cell line (hFOB1.19), and
      the potential bioactive factors involved in this process were investigated. The
      results suggested that hAEC-CM markedly promoted the proliferation, migration and
      osteogenic differentiation of hFOB1.19 cells. Expression of transforming growth
      factor beta1 (TGFbeta1) and microRNA 34a-5p (miR-34a-5p) were detected in hAECs.
      Furthermore, it was demonstrated that TGFbeta1 and miR-34a-5p stimulated the
      differentiation of hFOB1.19 cells, and that TGFbeta1 promoted cell migration.
      Moreover, the effects of hAEC-CM were downregulated following the depletion of
      either TGFbeta1 or miR-34a-5p. These results demonstrated that hAECs promote OB
      differentiation through the secretion of TGFbeta1 and miR-34a-5p, and that hAECs
      may be an optimal cell source in bone regenerative medicine.

PMID- 29207016
TI  - MicroRNA-21 promotes the progression of peritoneal fibrosis through the
      activation of the TGF-beta/Smad signaling pathway: An in vitro and in vivo study.
AB  - The present study aimed to explore the roles of microRNA-21 (miR-21) and the
      transforming growth factor-beta (TGF-beta)/Smad signaling pathway in the
      development of peritoneal fibrosis (PF). First, dialysis effluents from 30
      patients with PF were collected, and after the establishment of a mouse model of
      PF, hematoxylin and eosin (H&E) and Masson's staining were used to observe
      peritoneal tissues, inflammatory cells and blood vessels. High glucose was used
      to stimulate human peritoneal mesothelial cell lines and these stimulated cells
      were then transfected with miR-21 inhibitor. Immunofluorescence microscopy was
      applied for the observation of the transfected cells. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) was used to detect the
      expression of miR-21, and RT-qPCR and western blot analysis were used to detect
      the mRNA and protein expression of Zonula occludens-1 (ZO-1), TGF-beta, Smad,
      vimentin and connective-tissue growth factor (CTGF). The mRNA and protein
      expression levels TGF-beta, Smad-3, vimentin and CTGF were elevated, while ZO-1
      mRNA and protein expression was decreased with the prolonged duration of dialysis
      treatment in the patients with PF. The experiments using the mouse model of PF
      revealed that the peritoneal connective tissue was thickened, while the numbers
      of inflammatory cells and blood vessels were increased. The expression levels of
      miR-21, and the mRNA and protein expression levels of TGF-beta, Smad-3, vimentin
      and CTGF were increased over time, whereas the mRNA and protein expression levels
      ZO-1 constantly decreased in the mice in the experimental group. Moreoever, the
      expression of miR-21 positively correlated with the expression levels of TGF
      beta, Smad-3, vimentin and CTGF, while it negatively correlated with the
      expression of ZO-1. The results of H&E and Masson's staining revealed that miR-21
      expression was associated with the degree of PF. These findings thus indicate
      that miR-21 promotes the progression of PF through the activation of the TGF
      beta/Smad signaling pathway.

PMID- 29207017
TI  - A common African variant of human connexin 37 is associated with Caucasian
      primary ovarian insufficiency and has a deleterious effect in vitro.
AB  - Folliculogenesis requires communication between granulosa cells and oocytes,
      mediated by connexin-based gap junctions. Connexin 37 (Cx37)-deficient female
      mice are infertile. The present study assessed Cx37 deficiency in patients with
      primary ovarian insufficiency (POI). A candidate gene study was performed in
      patients and controls from the National Genotyping Center (Evry, France)
      including 58 Caucasian patients with idiopathic isolated POI and 142 Caucasian
      controls. Direct genomic sequencing of the coding regions of the GJA4 gene
      (encoding Cx37) was performed with the aim to identify a deleterious variant
      associated with POI and absent in ethnically matched controls. A single Cx37
      variant absent in the control population was identified, namely a c.946G>A
      heterozygous substitution leading to a p.Gly316Ser variant that was present in
      two POI patients. This variant was absent in all Caucasian controls from various
      databases, and has been observed exclusively in African populations. This variant
      was identified to have a dominant negative effect in HeLa cells in vitro to alter
      connexon function (by 67.2+/-7.17%), as determined by Gap-fluorescence recovery
      after photobleaching. The alteration principally resulted from a decrease of cell
      surface connexons due to altered trafficking (by 47.73+/-8.59%). In marked
      contrast to this observation, a p.Pro258Ser variant frequent in all ethnic
      populations in databases had no functional effect in vitro. In conclusion, the
      present study reported on a Cx37 variant in two Caucasian POI patients, which was
      absent in control Caucasian populations, and which had a deleterious effect in
      vitro. It is therefore suggested that in the genetic context of the Caucasian
      population, this variant may contribute to POI.

PMID- 29207018
TI  - Clinical significance of interleukin-6 and inducible nitric oxide synthase in
      ketamine-induced cystitis.
AB  - Ketamine is an ionotropic glutamatergic N-methyl-D-aspartate receptor antagonist,
      which is widely used among recreational drug abusers. Ketamine abusers exhibit
      substantially reduced bladder capacity, which can lead to urinary frequency. The
      molecular pathogenesis of ketamine-induced cystitis has been scarcely reported.
      Given previous clinical findings, it may be hypothesized that pathological
      alterations in smooth muscle cells (SMCs) of the urinary bladder serve a crucial
      role in the mechanism underlying cystitis. In the present study, two lineages of
      SMCs, one from differentiated foreskin-derived fibroblast-like stromal cells and
      the other from cultured normal aortic SMCs, were used to study ketamine-induced
      molecular alterations. Polymerase chain reaction was used to study the effects of
      ketamine on oxidative stress. The effects of adjuvant chemotherapy with
      cyclophosphamide (CTX) were also investigated. The results indicated that the
      expression levels of interleukin-6 and inducible nitric oxide synthase (iNOS)
      were decreased, whereas collagen expression and deposition were increased in
      ketamine-treated SMCs. Conversely, treatment with CTX restored the expression of
      iNOS, which may prevent or limit oxidative damage. In conclusion, the present
      study demonstrated that ketamine may induce several molecular alterations in SMCs
      and these changes may be associated with the clinical symptoms observed in
      ketamine abusers. In addition, the specific chemotherapeutic agent CTX may
      reverse these ketamine-induced aberrations.

PMID- 29207019
TI  - Stromal-epithelial lactate shuttle induced by tumor-derived interleukin-1beta
      promotes cell proliferation in oral squamous cell carcinoma.
AB  - Stromal-epithelial lactate shuttle is an essential process to support fast
      growing tumor cells, however, the underlying mechanism remains ambiguous.
      Interleukin-1beta (IL-1beta), which is a key node gene in both stromal and
      epithelial cells of oral squamous cell carcinoma (OSCC), may participate in this
      metabolic reprogramming. In the present study, anaerobic glycolysis of cancer
      associated fibroblasts (CAFs) was evaluated and the role of IL-1beta in
      regulating stromal-epithelial lactate shuttle was determined. A co-culture system
      of primary fibroblasts and OSCC cell lines (CAL27, UM1 or SCC25) was created to
      investigate the stromal-epithelial interaction. alpha-smooth muscle actin (alpha
      SMA) expression of fibroblasts, IL-1beta expression and cell proliferation of
      OSCC cells, and a series of glycolytic genes were measured. Recombinant IL-1beta
      treatment and IL-1beta knockdown in UM1 cells were also used to evaluate the
      effect of IL-1beta. Expression of alpha-SMA, glucose transporter 1, hexokinase 2,
      lactic dehydrogenase and mono-carboxylate transporter (MCT) 4 were significantly
      overexpressed in activated fibroblasts, while IL-1beta and MCT1 were upregulated
      in OSCC cells, indicating enhanced glycolysis in cells of the tumor stroma and a
      lactate shuttle to the tumor cells. Furthermore, exogenous IL-1beta induced
      fibroblasts to present similar expression profiles as that in the co-culture
      system. Silencing of IL-1beta significantly abrogated the regulatory effect of
      UM1 cells on stromal glycolysis. Additionally, carboxy-fluorescein succinimidyl
      ester cell tracing indicated that OSCC cell proliferation was accelerated during
      co-cultivation with fibroblasts. These results indicate that tumor-derived IL
      1beta enhanced stromal glycolysis and induced one-way lactate flow from the tumor
      mesenchyme to transformed epithelium, which promotes OSCC proliferation.

PMID- 29207020
TI  - Quercetin inhibits okadaic acid-induced tau protein hyperphosphorylation through
      the Ca2+-calpain-p25-CDK5 pathway in HT22 cells.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by
      aberrant tau protein hyperphosphorylation, which eventually leads to the
      formation of neurofibrillary tangles. Hyperphosphorylated tau protein is
      considered as a vital factor in the development of AD and is highly associated
      with cognitive impairment. Therefore, it is recognized to be a potential
      therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound.
      In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced
      tau protein hyperphosphorylation in HT22 cells was explored. Western blotting
      results indicated that QUE significantly attenuated OA-induced tau protein
      hyperphosphorylation at the Ser396, Ser199, Thr231 and Thr205 sites. Further
      experiments demonstrated that QUE inhibited the activity of cyclin-dependent
      kinase 5 (CDK5), a key enzyme in the regulation of tau protein, and blocked the
      Ca2+-calpain-p25-CDK5 signaling pathway. These observations indicate the ability
      of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the
      associated neuropathology. In conclusion, these results support the potential of
      QUE as a therapeutic agent for AD and other neurodegenerative tauopathies.

PMID- 29207021
TI  - Stromal cell-derived factor-1 induces matrix metalloproteinase expression in
      human endplate chondrocytes, cartilage endplate degradation in explant culture,
      and the amelioration of nucleus pulposus degeneration in vivo.
AB  - Intervertebral disc (IVD) degeneration is a strong etiological factor in chronic
      lower back pain. Stem cell migration toward the site of IVD degeneration for
      regeneration is restricted by avascularity and distance. Our previous study
      indicated that the expression of stromal cell-derived factor-1 (SDF-1) and its
      receptor, C-X-C chemokine receptor type 4 (CXCR4) was upregulated in degenerated
      cartilage endplate (CEP) and nucleus pulposus (NP). In the present study, SDF-1
      increased CXCR4 mRNA and protein expression in human endplate chondrocytes in a
      dose-dependent manner. The results of reverse transcription-quantitative
      polymerase chain reaction, western blotting and zymography indicated that SDF-1
      increased matrix metalloproteinase (MMP)-1, -3 and -13 mRNA and protein
      expression in human endplate chondrocytes in a dose-dependent manner. The results
      of zymography suggested that SDF-1 also increased MMP-2 and -9 protein expression
      in a dose-dependent manner. The CXCR4-specific chemical inhibitor AMD3100
      significantly decreased the levels of MMP-1, -2, -3, -9 and -13 expression. In a
      human cartilage explant culture model, SDF-1 accelerated the degradation of
      extracellular matrix (ECM), and AMD3100 decreased cartilage cleavage. However, in
      a rat tail disc degeneration model, the injection of SDF-1 into the NP resulted
      in the retention of dense areas of proteoglycan matrix and enhanced NP
      regeneration. These results suggest that SDF-1, as an inflammatory cytokine,
      induces MMP expression in human endplate chondrocytes and that ECM remodeling in
      the CEP may be a favorable factor of endogenous stem cell homing into the NP for
      regeneration in vivo.

PMID- 29207022
TI  - Role of the c-Jun N-terminal kinase signaling pathway in the activation of
      trypsinogen in rat pancreatic acinar cells.
AB  - Bile acid causes trypsinogen activation in pancreatic acinar cells through a
      complex process. Additional research is required to further elucidate which
      signaling pathways affect trypsinogen activation when activated. the changes in
      the whole-genome expression profile of AR42J cells under the effect of
      taurolithocholic acid 3-sulfate (TLC-S) were investigated. Furthermore, gene
      groups that may play a regulatory role were analyzed using the modular approach
      of biological networks. The aim of the present study was to improve our
      understanding of the changes in TLC-S-stimulated AR42J cells through a genetic
      functional modular analysis. whole-genome expression profile chip arrays were
      applied to detect genes that were differentially expressed in pancreatic acinar
      AR42J cells treated with TLC-S for 20 min. Based on the human protein reference
      database, a protein-protein interaction network was obtained, which was then
      processed by CFinder software to derive 14 modules. Among these 14 modules, the
      gene ontology biological processes enrichment analysis identified two as modules
      of interest. Kyoto encyclopedia of genes and genomes map analysis revealed that
      MAP2K4, MAPK8 and FLNA are part of the c-Jun N-terminal kinase (JNK) pathway. The
      JNK signaling pathway is involved in regulating trypsinogen activation in rat
      pancreatic AR42J cells. Next, a regulatory network of seven kinase inhibitors was
      constructed. SP600125 is an ATP-competitive, efficient, selective and reversible
      inhibitor of JNK. the results were verified by four sets of experiments and
      demonstrated that trypsinogen activation is mediated by the JNK signaling pathway
      in the pathogenesis of acute pancreatitis (AP). The present study provided a
      useful reference for better understanding the pathogenesis of AP and identifying
      new targets to regulate trypsinogen activation, in addition to providing valuable
      information for the treatment of AP.

PMID- 29207023
TI  - Macrophage migration inhibitory factor promotes Warburg effect via activation of
      the NF-kappaB/HIF-1alpha pathway in lung cancer.
AB  - Macrophage migration inhibitory factor (MIF) is upregulated in various solid
      tumors, a process that is associated with tumor progression and metastasis. The
      present study aimed to investigate the role and the underlying mechanism of MIF
      in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and
      A549 cell lines were used to examine the expression of MIF by real time
      quantitative polymerase chain reaction and western blotting. The lentivirus was
      used to overexpress MIF and the expression of MIF and hypoxia-inducible factor 1
      alpha (HIF-1alpha) were knocked down by shRNA or siRNA. The proliferation of cell
      lines was detected by MTT assay. Glucose uptake, adenosine 5'-triphosphate (ATP)
      production, the glycolytic rate and lactate production were used to examine the
      Warburg effect in cells. BAY 11-7082 (BAY) was used to inhibit the nuclear
      translocation of nuclear factor-kappaB (NF-kappaB), which was detected using
      immunofluorescence. It was revealed that overexpression of MIF promoted cell
      proliferation and the Warburg effect in lung cancer, whereas knockdown of MIF
      inhibited cell proliferation and the Warburg effect. Mechanistically, MIF
      promoted the Warburg effect by upregulating HIF-1alpha. Knockdown of HIF-1alpha
      largely abolished the promotional effect of MIF on the Warburg effect.
      Additionally, the results in the current study provided evidence that MIF
      regulates HIF-1alpha through NF-kappaB. In conclusion, the findings of the
      present study demonstrated that MIF is a key component in lung cancer progression
      through promoting the Warburg effect, and that the novel MIF/NF-kappaB/HIF-1alpha
      axis may prove to be useful for the development of new strategies for treating
      patients with lung cancer.

PMID- 29207024
TI  - Geraniin protects bone marrow-derived mesenchymal stem cells against hydrogen
      peroxide-induced cellular oxidative stress in vitro.
AB  - Administration of bone marrow-derived mesenchymal stem cells (MSCs) has emerged
      as a potential therapeutic approach for the treatment of myocardial infarction
      (MI). However, the increase in reactive oxygen species (ROS) in ischemic cardiac
      tissue compromises the survival of transplanted MSCs, thus resulting in limited
      therapeutic efficiency. Therefore, strategies that attenuate oxidative stress
      induced damage and enhance MSC viability are required. Geraniin has been reported
      to possess potent antioxidative activity and exert protective effects on numerous
      cell types under certain conditions. Therefore, geraniin may be considered a
      potential drug used to modulate MSC-based therapy for MI. In the present study,
      MSCs were pretreated with geraniin for 24 h and were exposed to hydrogen peroxide
      (H2O2) for 4 h. Cell apoptosis, intracellular ROS levels and mitochondrial
      membrane potential were measured using Annexin V-fluorescein
      isothiocyanate/propidium iodide staining, the 2',7'-dichlorodihydrofluorescein
      diacetate fluorescent probe and the membrane permeable dye JC-1, respectively.
      Glutathione and malondialdehyde levels were also investigated. The expression
      levels of apoptosis-associated proteins and proteins of the phosphoinositide 3
      kinase (PI3K)/protein kinase B (Akt) signaling pathway were analyzed by western
      blotting. The results demonstrated that geraniin could significantly attenuate
      H2O2-induced cell damage by promoting MSC survival, reducing cellular ROS
      production and maintaining mitochondrial function. Furthermore, geraniin
      modulated the expression levels of phosphorylated-Akt in a time- and dose
      dependent manner. The cytoprotective effects of geraniin were suppressed by
      LY294002, a specific PI3K inhibitor. In conclusion, the present study revealed
      that geraniin protects MSCs from H2O2-induced oxidative stress injury via the
      PI3K/Akt pathway. These findings indicated that cotreatment of MSCs with geraniin
      may optimize therapeutic efficacy for the clinical treatment of MI.

PMID- 29207025
TI  - Anti-obesity effects of pectinase and cellulase enzyme-treated Ecklonia cava
      extract in high-fat diet-fed C57BL/6N mice.
AB  - The present study investigated the anti-obesity effects of enzyme-treated
      Ecklonia cava extract (EEc) in C57BL/6N mice with high-fat diet (HFD)-induced
      obesity. The EEc was separated and purified with the digestive enzymes pectinase
      (Rapidase X-Press L) and cellulase (Rohament CL) and its effects on the
      progression of HFD-induced obesity were examined over 10 weeks. The mice were
      divided into 6 groups (n=10/group) as follows: Normal diet group, HFD group, mice
      fed a HFD with 25 mg/kg/day Garcinia cambogia extract and mice fed a HFD with 5,
      25 or 150 mg/kg/day EEc (EHD groups). Changes in body weight, fat, serum lipid
      levels and lipogenic enzyme levels were determined. The body weight and liver
      weight were increased in the HFD group compared with those in the ND group, which
      was significantly reduced by EEc supplementation. In addition, significant
      reductions in epididymal, perirenal and mesenteric white adipose tissues were
      present in the EHD groups and all three EHD groups exhibited decreases in
      insulin, leptin and glutamate pyruvate transaminase levels compared with those in
      the HFD group. In addition, EEc treatment significantly decreased the serum and
      hepatic triglyceride levels compared with those in the HFD group. However, the
      levels of high-density lipoprotein cholesterol/total cholesterol ration increased
      significantly in EHD-25 and -150 groups compared with those in the HFD group.
      Changes in adipogenic and lipogenic protein expression in the liver was assessed
      by western blot analysis. The EHD-25 and -150 groups exhibited reduced levels of
      CCAAT/enhancer-binding protein alpha and peroxisome proliferator activated
      receptor gamma. However, the phosphorylation ratios of AMP-activated protein
      kinase and acetyl-CoA carboxylase were significantly increased in the liver
      tissue obtained from the EHD (5, -25 and -150 mg/kg/day) groups compared with
      those in the HFD group. EEc supplementation reduced levels of sterol regulatory
      element-binding protein-1c, adipose fatty acid-binding protein, fatty acid
      synthase and leptin, while it significantly increased glucose transporter type 4
      and adiponectin protein levels in the liver tissues of all three EHD groups
      compared with those in the HFD group. Taken together, these results suggest that
      EEc exerts anti-obesity effects by reducing body weight and the serum and hepatic
      levels of obesity-associated factors. Thus, EEc supplementation reduces HFD
      induced obesity in C57BL/6N mice and has the potential to prevent obesity and
      subsequent metabolic disorders.

PMID- 29207026
TI  - Comparative analysis of human embryonic stem cell-derived neural stem cells as an
      in vitro human model.
AB  - Alternative cell models of human neural stem cells (hNSCs) have been developed
      and used for investigations ranging from in vitro experiments to in vivo clinical
      studies. However, a cell model capable of mimicking the 'normal' state of hNSCs
      is mandatory in order to extrapolate the results of these studies to humans. In
      the present study, to select a more suitable hNSC model for developing human
      based experimental platforms, two representative hNSC types were compared, namely
      human embryonic stem cell (hESC)-derived hNSCs and ReNcell CX cells, which are
      well-characterized immortalized hNSC lines. The hNSCs, differentiated from hESCs
      via human neuroectodermal sphere (hNES) formation, recapitulated the molecular
      and cellular phenotypes of hNSCs, including NSC marker expression and terminal
      neuronal differentiation potential. Comparative analyses of the transcriptome
      profiles of the hESC-derived hNESs and ReNcell CX hNSCs showed that the
      differentiated hNESs were analogous to the ReNcell CX cells, as demonstrated by
      principal component analysis and hierarchical sample clustering. The hNSC
      specific transcriptome was presented, comprising commonly expressed transcripts
      between hNESs derived from hESCs and ReNcell CX cells. To elucidate the molecular
      mechanisms associated with the hNSC identity, the hNSC-specific transcriptome was
      analyzed using pathway and functional annotation clustering analyses. The results
      suggested that hESC-derived hNESs, an expandable and accessible cell source, may
      be used as a relevant hNSC model in a wide range of neurological investigations.

PMID- 29207028
TI  - Role of the cofilin 2 gene in regulating the myosin heavy chain genes in mouse
      myoblast C2C12 cells.
AB  - The cofilin 2 (CFL2) and myosin heavy chain (MyHC) genes play a key role in
      muscle development and myofibrillar formation. The aim of the present study was
      to investigate the effect of CFL2 on genes involved in fiber formation and the
      mechanisms underlying this process. Undifferentiated and differentiated C2C12
      cells (UDT and DT, respectively) were transfected with CFL2 small interfering RNA
      (siRNA). CFL2 mRNA and protein levels were assessed using reverse transcription
      polymerase chain reaction (RT-PCR) and western blotting, respectively. MyHC gene
      expression in UDT and signaling pathway-related factors were observed with
      quantitative PCR (RT-qPCR) and western blotting. Fluorescence microscopy was used
      to analyze the cytoskeletal effects of CFL2. The mRNA and protein expressions of
      CFL2, four MyHC isoforms (MyHC-I, MyHC-IIa, MyHC-IIb and MyHC-IIx), p38 mitogen
      activated protein kinase, cAMP-response element-binding protein, AMP-activated
      protein kinase alpha1, and myocyte enhancer factor 2C, were significantly
      decreased in UDT. However, extracellular signal-regulated kinase 2 expression was
      significantly increased. Slightly decreased CFL2 protein and mRNA expression was
      observed in DT C2C12 cells transfected with CFL2 siRNA. Fluorescence microscopy
      revealed a significant decrease of CFL2 in the cytoplasm, but not the nucleus, of
      UDT, compared with normal cells. These results indicated that the mouse CFL2 gene
      may be involved in the regulation of MyHC via the key signaling molecules of CFL2
      related signaling pathways.

PMID- 29207029
TI  - Icariin possesses chondroprotective efficacy in a rat model of dexamethasone
      induced cartilage injury through the activation of miR-206 targeting of cathepsin
      K.
AB  - The present study aimed to investigate the articular cartilage and chondrocytes
      of dexamethasone (DXM)-induced cartilage injuries in rats in response to
      treatment with icariin, as well as the implicated molecular mechanism. Effects of
      icariin on bone metabolism and articular cartilage in experimental rats were
      investigated. Subsequently, the present study assessed dysregulated microRNA
      (miRNA) in the articular cartilage of experimental rats, and validated the
      significant miRNA and their targets. Finally, the effects of icariin on
      chondrocytes in experimental rats and the implicated molecular mechanism were
      explored. Quantitative polymerase chain reaction demonstrated that icariin
      significantly reversed DXM-induced bone degradation and stimulated bone
      regeneration. In addition, some notable changes in articular cartilage were also
      observed following continuous administration of icariin to DXM-treated rats,
      including enhanced cartilage area (revealed by safranin-O staining), substantial
      decrements in serum concentrations of deoxypyridinoline and C-terminal
      telopeptide of type II collagen, reduced expression of collagen type I and matrix
      metalloproteinase-13, as well as elevated expression of transforming growth
      factor-beta. Furthermore, miR-206 was determined to be significantly upregulated
      in the icariin group compared with the DXM-treated group. A luciferase assay
      further validated cathepsin K as the target RNA of miR-206. Additionally, icariin
      (100 uM) facilitated the viability of chondrocytes and reduced apoptotic
      chondrocytes. More importantly, icariin (100 uM) not only abolished the
      inhibition effect of DXM on miR-206 expression in chondrocytes, but also
      eliminated the enhancing effect of DXM on cathepsin K expression. Overall, the
      present study identified icariin as a novel therapeutic agent in DXM-induced
      cartilage injury in rats, and revealed that the activation of miR-206 targeting
      of cathepsin K may be responsible for the chondroprotective efficacy of icariin.

PMID- 29207027
TI  - Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy
      (Review).
AB  - Galectin-3 is a member of the galectin family, which are beta-galactoside-binding
      lectins with >=1 evolutionary conserved carbohydrate-recognition domain. It binds
      proteins in a carbohydrate-dependent and -independent manner. Galectin-3 is
      predominantly located in the cytoplasm; however, it shuttles into the nucleus and
      is secreted onto the cell surface and into biological fluids including serum and
      urine. It serves important functions in numerous biological activities including
      cell growth, apoptosis, pre-mRNA splicing, differentiation, transformation,
      angiogenesis, inflammation, fibrosis and host defense. Numerous previous studies
      have indicated that galectin-3 may be used as a diagnostic or prognostic
      biomarker for certain types of heart disease, kidney disease and cancer. With
      emerging evidence to support the function and application of galectin-3, the
      current review aims to summarize the latest literature regarding the biomarker
      characteristics and potential therapeutic application of galectin-3 in associated
      diseases.

PMID- 29207030
TI  - Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3
      inflammasome.
AB  - Damage to the bronchial epithelium leads to persistent inflammation and airway
      remodelling in various respiratory diseases, such as asthma and chronic
      obstructive pulmonary disease. To date, the mechanisms underlying bronchial
      epithelial cell damage and death by common allergens remain largely unknown. The
      aim of the present study was to investigate Der f1, an allergen of
      Dermatophagoides farinae, which may result in the death of human bronchial
      epithelial cells (HBECs). Der f1 induces BECs to undergo the inflammatory cell
      death referred to as pyroptosis, induced by increasing lactate dehydrogenase
      release and propidium iodide penetration. Stimulation by Der f1 enhances
      interleukin (IL)-1beta cleavage and release, which is associated with caspase-1
      activation. In addition, the NOD-like receptor family pyrin domain-containing 3
      (NLRP3), is required for the activation of caspase-1 through increasing the
      formation of the inflammasome complex. Consistent with these findings, pre
      treatment of HBECs with a caspase-1 inhibitor, or silencing of NLRP3 by siRNA
      transfection, reduced Der f1-mediated IL-1beta and pyroptosis. Therefore, the
      common allergen Der f1 was not only found to induce allergy, but also led to
      pyroptosis and IL-1beta secretion via the NLRP3-caspase-1 inflammasome in HBECs.
      This newly identified connection of the Der f1 allergen with BEC damage and
      inflammation may play an important role in the pathogenesis of asthma.

PMID- 29207031
TI  - PRL-3 increases the aggressive phenotype of prostate cancer cells in vitro and
      its expression correlates with high-grade prostate tumors in patients.
AB  - The increased expression of phosphatase of regenerating liver-3 (PRL-3) has been
      shown to be associated with the aggressive and metastatic phenotype of different
      solid tumors. However, it is not known whether PRL-3 plays a similar role in the
      progression of prostate cancer (PCa). In this study, immunoblot analysis of
      androgen receptor (AR)-positive PCa lines (LNCaP and LNCaP-SF) revealed the
      constitutive cytoplasmic expression of PRL-3, and stimulation with R1881 (AR
      agonist) rapidly increased the nuclear translocation of PRL-3. The AR-negative
      cell lines exhibited negligible PRL-3 expression, and the ectopic overexpression
      of PRL-3 increased both the proliferative and invasive potential of PC3 and DU145
      cells. In addition, we measured PRL-3 protein expression in human prostate tumor
      sections. A high-density prostate tumor microarray (TMA) was immunostained to
      assess whether PRL-3 expression and its subcellular localization (cytoplasmic and
      nuclear levels) is associated with the Gleason score (GS), Gleason grade (GG) and
      tumor stage (T-stage). Digital image analysis (DIA) revealed that PRL-3
      expression was significantly higher in the malignant cores, as compared to the
      non-malignant areas. Increases in both total and nuclear PRL-3 levels were also
      associated with a higher GS and GG. Metastatic tumors (T4-stage) had lower
      cytoplasmic, but higher nuclear PRL-3 levels. Furthermore, the
      nuclear/cytoplasmic ratio for PRL-3 in the tumors graded as GS7 could effectively
      distinguish between indolent (3+4) and aggressive (4+3) disease. Thus, our
      experiments using PCa lines suggested that PRL-3 is an AR-regulated gene and its
      androgen-induced nuclear localization may increase the aggressive behavior of PCa
      cells. Furthermore, the digital analysis of immunostained tumor sections
      suggested that PRL-3 may be an effective biomarker of high-grade PCa, and its
      nuclear/cytoplasmic ratio may be used to distinguish between indolent vs.
      aggressive tumors.

PMID- 29207032
TI  - Autophagy relieves the function inhibition and apoptosis-promoting effects on
      osteoblast induced by glucocorticoid.
AB  - Autophagy may be a major mechanism by which osteoblasts (OBs) protect against the
      negative effects of chronic glucocorticoid (GC) usage. OBs are closely associated
      with the remodeling that occurs in GC-induced osteoporosis (GIO). In osteocytes,
      in response to stress induced by GCs, several pathways are activated, including
      cell necrosis, apoptosis and autophagy. However, the role of autophagy in OBs
      following treatment with excess GCs has not been addressed. In the current study,
      confocal microscopy observation of green fluorescent protein-microtubule
      associated protein 1 light chain 3beta (LC3) punctuate, and western blotting for
      LC3II and Beclin 1 were performed for detection of autophagy in the MC3T3-E1
      osteoblastic cell line. Flow cytometry and western blotting were used for the
      examination of apoptosis and expression of BAX apoptosis regulator
      (Bax)/apoptosis regulator Bcl-2 (Bcl-2). The expression of genes associated with
      osteoblastic function, runt-related transcription factor 2, alpha-1 type 1
      collagen and osteocalcin, were measured by reverse transcription-quantitative
      polymerase chain reaction. The results indicated that autophagy was induced in
      OBs during dexamethasone (Dex) treatment in a dose-dependent manner. The level of
      autophagy did not continue to increase over time, but peaked at 48 h and then
      decreased gradually. Subsequently, flow cytometry was used to demonstrate that
      inhibition of autophagy induced apoptosis in OBs under Dex treatment, and was
      associated with the upregulation of Bax and the downregulation of Bcl-2 protein
      expression. Furthermore, the data suggested that the inhibition of autophagy also
      suppressed the expression of osteoblastic genes. By contrast, the stimulation of
      autophagy maintained the gene expression level under Dex treatment. The data
      revealed that autophagy is an important regulator of osteoblastic apoptosis
      through its interaction with Bax/Bcl-2, and maintains the osteoblastic function
      of MC3T3-E1 cells following GC exposure. In addition, these results indicated
      that the suppression of autophagy in OBs under chronic GC therapy may increase
      the prevalence of GIO and fragility fractures.

PMID- 29207033
TI  - Epigallocatechin-3-gallate inhibits inflammation and epithelial-mesenchymal
      transition through the PI3K/AKT pathway via upregulation of PTEN in asthma.
AB  - Asthma is a chronic disease associated with hyperresponsiveness, obstruction and
      remodeling of the airways. Epithelial-mesenchymal transition (EMT) has an
      important role in these alterations and may account for the accumulation of
      subepithelial mesenchymal cells, thus contributing to airway hyperresponsiveness
      and remodeling. Epigallo-catechin-3-gallate (EGCG), which is a type of
      polyphenol, is the most potent ingredient in green tea, and exhibits
      antibacterial, antiviral, antioxidative, anticancer and chemopreventive
      activities. Recently, numerous studies have investigated the protective effects
      of EGCG against asthma and other lung diseases. In the present study, the role of
      EGCG in ovalbumin (OVA)-challenged asthmatic mice was determined. In addition,
      the inhibitory effects of EGCG against transforming growth factor (TGF)-beta1
      induced EMT and migration of 16HBE cells, and the underlying mechanisms of the
      phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, were
      investigated by immunofluorescence, Transwell, wound healing assay and western
      blot analysis, respectively. The results indicated that EGCG may suppress
      inflammation and inflammatory cell infiltration into the lungs of OVA-challenged
      asthmatic mice, and may also inhibit EMT via the PI3K/Akt signaling pathway
      through upregulating the expression of phosphatase and tensin homolog (PTEN) in
      vivo and in vitro. The present study also revealed the anti-migratory effects of
      EGCG in TGF-beta1-induced 16HBE cells, thus suggesting it may reduce airway
      remodeling. The present study provides a novel insight into understanding the
      protective effects of EGCG on airway remodeling in asthma, and indicates that
      EGCG may be useful as an adjuvant therapy for bronchial asthma.

PMID- 29207034
TI  - Role of inhibitor of growth 4 in the suppression of human melanoma cells through
      the Fas/FasL-mediated apoptosis pathway.
AB  - Melanoma, the most aggressive form of skin cancer, is notoriously resistant to
      all current available therapies. Inhibitor of growth 4 (ING4), a novel member of
      the ING family of proteins, has previously been shown to play a critical role in
      the development of multiple tumors by regulating apoptosis, proliferation, cell
      cycle progress, migration and invasion. However, the functional role of ING4 in
      human melanoma remains unclear. To fully understand its potential role in human
      melanoma, in the present study, lentivirus (LV)-ING4 and LV-ING4-short hairpin
      RNA were constructed and transfected into human melanoma A375 cells. First, the
      effect of overexpressing or downregulating ING4 on the apoptosis of the
      transfected melanoma cells and cluster of differentiation (CD)3+ T cells was
      investigated. In the present study, we found that the late apoptotic cells, and
      not the early apoptotic cells, were more in LV-ING4 group compared with LV
      control, and both the early and late apoptosis of CD3+ T cells was significantly
      observed in A375 cells transfected with LV-ING4 compared with LV-control.
      Importantly, it was determined whether the overexpression of ING4 significantly
      induce apoptotic cell death via Fas/FasL (Fas death receptor/FasL) pathway
      activation and downregulation of poly(ADP-ribose) polymerase, caspase-3 and
      caspase-8 in the melanoma cells and CD3+ T cells. These results demonstrated that
      overexpression of ING4 can induce the apoptosis of melanoma cells and CD3+ T
      cells through signaling pathways such as the Fas/FasL pathway, and that ING4 gene
      therapy for melanoma treatment is a novel approach.

PMID- 29207035
TI  - In vitro characterization of spheres derived from colorectal cancer cell lines.
AB  - Spherical cultures (SCs) can be regarded in cancer research as a link between in
      vitro investigations on cancer lines and in vivo studies of tumor development.
      SCs are believed to mimic tumor architecture and to be enriched in cancer stem
      cell-like cells (CSC-like cells). In the present study we characterized
      colonospheres derived from colorectal cancer (CRC) cell lines, and we confirmed
      the ability of HCT116 and HT29 cell lines to form spheres within serum-free
      medium, however, the detailed analysis presented the major differences concerning
      their characteristics including morphology, phenotype, proliferative potential,
      distribution in the cell cycle phases and spherogenicity. Moreover, after we
      magnetically separated CD133+ and CD133- cells we could conduct the analogical
      analysis as we performed for the original cells. We observed that all cellular
      fractions unveiled sphere formation capacity, even when cultured in limited
      number of cells per well and only SCs originated from CD133+ fraction resembled
      morphologically the parental spheres. Both CD133+ and CD133- subsets derived from
      HCT116 line were more enriched in cells in G0/G1 phase of the cell cycle in
      comparison to their HT29 analogues. Additionally, proliferative potential also
      varied amongst all studied fractions. Surprisingly, 3-D invasion assay revealed
      that only HCT116-derived populations were able to migrate into extended regions
      of Matrigel Matrix confirming their higher aggressiveness. Our results provided
      comprehensive characterization of CRC cell lines culture in adherent and
      spherical forms and, what seems to be the most advantageous, the comparison of
      two distinct fractions after magnetic separation. As we found the specific
      features of cells presented line- and expansion mode-dependency, thus, such
      complete description might appear crucial before CRC lines would be involved into
      sophisticated assays, especially focused on potentially novel therapeutic agents
      targeting CSC-like cells.

PMID- 29207036
TI  - Periostin has a protective role in melatonin-induced cell apoptosis by inhibiting
      the eIF2alpha-ATF4 pathway in human osteoblasts.
AB  - The present study aimed to investigate the role of periostin (POSTN) and high
      melatonin concentrations in the apoptosis of hFOB 1.19 human normal fetal
      osteoblastic cells. hFOB 1.19 human osteoblastic cells were stably cultured and
      treated in different concentrations of melatonin for different durations of
      action. Apoptosis was assessed quantitatively using flow cytometric analysis. The
      results of western blot analysis demonstrated that the treatment of cells with
      different concentrations of melatonin for different durations of action revealed
      a positive association between melatonin and the expression levels of glucose
      regulated protein (GRP)78, GRP94, phosphorylated (p-) eukaryotic initiation
      factor 2alpha (eIF2alpha), activating transcription factor (ATF)4, CCAAT/enhanced
      binding protein homologous protein (CHOP), cleaved caspase-3, p-c-Jun N-terminal
      kinase (JNK) and POSTN. When POSTN was inhibited, the levels of p-JNK, CHOP, p
      eIF2alpha, ATF4 and cleaved caspase-3 were significantly increased, whereas other
      proteins associated with the endoplasmic reticulum stress (ERS) pathways,
      including ATF6 and X-box binding protein 1 (XBP1), were not significantly
      altered. Reverse transcription-quantitative polymerase chain reaction analysis
      was also performed to assess the relative mRNA levels of ATF4, ATF6 and XBP1. The
      results of the present study are the first, to the best of our knowledge, to
      demonstrate that melatonin induced apoptosis in hFOB 1.19 human osteoblastic
      cells by activating the ERS-associated eIF2alpha-ATF4 pathway and subsequently
      triggered the cascade effects of CHOP, caspase-3 and JNK. POSTN may function as a
      protective factor for osteoblasts during this process by inhibiting the eIF2alpha
      ATF4 pathway.

PMID- 29207037
TI  - Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7
      macrophages and DNCB-induced atopic dermatitis animal models.
AB  - Flavonols are compounds that have been shown to possess potent anti-inflammatory
      effects in cellular and animal models of inflammation. In the present study, the
      anti-inflammatory effects and mechanisms of two natural flavonols, quercetin and
      galangin, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were
      investigated. It was identified that quercetin and galangin markedly reduced the
      production of nitric oxide (NO), inducible NO synthase and interleukin-6, and the
      nuclear translocation of nuclear factor-kappaB (NF-kappaB). In addition, LPS
      induced activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and c
      Jun N-terminal kinase (JNK) was suppressed by quercetin and galangin. Taken
      together, these data implied that NF-kappaB, Erk1/2 and JNK may be potential
      molecular targets of quercetin and galangin in an LPS-induced inflammatory
      response. Subsequently, the effects of oral administration of quercetin or
      galangin, either alone or in combination, in a 2,4-dinitrochlorobenzene-induced
      atopic dermatitis (AD) mouse model were investigated. As a result, measurements
      of ear thickness and the levels of serum immunoglobulin E, and histological
      analysis revealed that the two flavonols led to a decrease in inflammation,
      whereas, in combination, they were even more effective. These results suggested
      that quercetin and galangin may be promising therapeutic agents for AD.
      Additionally, their combination may be a novel therapeutic strategy for the
      prevention of AD.

PMID- 29207038
TI  - Interaction of iPSC-derived neural stem cells on poly(L-lactic acid) nanofibrous
      scaffolds for possible use in neural tissue engineering.
AB  - Tissue engineering is a rapidly growing technological area for the regeneration
      and reconstruction of damage to the central nervous system. By combining seed
      cells with appropriate biomaterial scaffolds, tissue engineering has the ability
      to improve nerve regeneration and functional recovery. In the present study,
      mouse induced pluripotent stem cells (iPSCs) were generated from mouse embryonic
      fibroblasts (MEFs) with the non-integrating episomal vectors pCEP4-EO2S-ET2K and
      pCEP4-miR-302-367 cluster, and differentiated into neural stem cells (NSCs) as
      transplanting cells. Electrospinning was then used to fabricate randomly oriented
      poly(L-lactic acid) (PLLA) nanofibers and aligned PLLA nanofibers and assessed
      their cytocompatibility and neurite guidance effect with iPSC-derived NSCs
      (iNSCs). The results demonstrated that non-integrated iPSCs were effectively
      generated and differentiated into iNSCs. PLLA nanofiber scaffolds were able to
      promote the adhesion, growth, survival and proliferation of the iNSCs.
      Furthermore, comp-ared with randomly oriented PLLA nanofibers, the aligned PLLA
      nanofibers greatly directed neurite outgrowth from the iNSCs and significantly
      promoted neurite growth along the nanofibrous alignment. Overall, these findings
      indicate the feasibility of using PLLA nanofiber scaffolds in combination with
      iNSCs in vitro and support their potential for use in nerve tissue engineering.

PMID- 29207039
TI  - Effective component of Salvia miltiorrhiza in promoting cardiomyogenic
      differentiation of human placenta-derived mesenchymal stem cells.
AB  - Our previous study indicated that Salvia miltiorrhiza (SM) induced human placenta
      derived mesenchymal stem cells (hPDMSCs) to differentiate into cardiomyocytes,
      however, the effective component of SM in promoting cardiomyogenic
      differentiation remained to be elucidated. In the present study, the most
      commonly examined components of SM, including danshensu, salvianolic acid B,
      protocatechuic aldehyde, tanshinone I (TS I), TS IIA and cryptotanshinone, were
      used to determine the effective components of SM in promoting cardiomyogenic
      differentiation. The above components of SM slowed cell growth rate and altered
      cell morphology with a spindle or irregular shape to different degrees. The cells
      treated with the above components of SM showed increasing of cardiac protein
      expression to differing degrees, including GATA-binding protein 4, atrial
      natriuretic factor, alpha-sarcomeric actin and cardiac troponin-I. Among the
      components of SM, TS IIA induced the most marked effects. In addition, the above
      components of SM increased the expression of phosphorylated glycogen synthase
      kinase-3beta, but decreased the expression of beta-catenin to different degrees,
      with TS IIA also having the most marked effects. In conclusion, the results of
      the present study suggested that TS IIA was the most effective active component
      of SM in inducing hPDMSCs to differentiate into cardiomyocytes, and that Wnt/beta
      catenin signaling was important in the process of TS IIA promoting cardiomyogenic
      differentiation.

PMID- 29207041
TI  - Mitochondria-mediated damage to dopaminergic neurons in Parkinson's disease
      (Review).
AB  - Mitochondria are important organelles in virtually all eukaryotic cells, and are
      involved in a wide range of physiological and pathophysiological processes.
      Besides the generation of cellular energy in the form of adenosine triphosphate,
      mitochondria are also involved in calcium homeostasis, reactive oxygen species
      production and the activation of the intrinsic cell death pathway, thus
      determining cell survival and death. Mitochondrial abnormalities have been
      implicated in a wide range of disorders, including neurodegenerative disease such
      as Parkinson's disease (PD), and considered as a primary cause and central event
      responsible for the progressive loss of dopaminergic neurons in PD. Thus,
      reversion or attenuation of mitochondrial dysfunction should alleviate the
      severity or progression of the disease. The present review systematically
      summarizes the possible mechanisms associated with mitochondria-mediated
      dopaminergic neuron damage in PD, in an attempt to elucidate the requirement for
      further studies for the development of effective PD treatments.

PMID- 29207040
TI  - Aryl hydrocarbon receptor inhibits inflammation in DSS-induced colitis via the
      MK2/p-MK2/TTP pathway.
AB  - The pathogenesis of inflammatory bowel disease (IBD) is believed to be associated
      with the abnormal expression of inflammatory factors. The aryl hydrocarbon
      receptor (AhR) is a ligand-dependent transcription factor, which can suppress the
      inflammatory response and attenuate experimental colitis. However, the detailed
      mechanism underlying the effects of AhR remains unclear. The present study
      investigated the role of AhR in the pathogenesis of IBD. Colitis was induced in
      mice by administration of 3% dextran sulphate sodium (DSS) for 7 days. The mice
      were also administered injections of the AhR agonist, 6-formylindolo(3,2
      b)carbazole (FICZ), starting 2 days after the first administration of DSS.
      Furthermore, LoVo cells were treated with lipopolysaccharide (LPS) in the
      presence or absence of FICZ for 8 h. The protein expression levels of AhR,
      cytochrome P450 1A1 (CYP1A1) and tristetraprolin (TTP) were assessed by western
      blotting and immunofluorescence, whereas mRNA expression levels were assessed by
      reverse transcription-quantitative polymerase chain reaction. The results
      indicated that injection of mice with FICZ significantly attenuated DSS-induced
      colitis; in addition, the expression levels of inflammatory cytokines were
      markedly downregulated. Conversely, the expression levels of AhR and TTP were
      upregulated. In addition, mice in the AhR-knockout + DSS group exhibited elevated
      inflammatory cytokine production and developed more severe colitis. In LoVo
      cells, incubation with FICZ decreased the expression levels of inflammatory
      cytokines, whereas AhR and TTP expression was increased. In addition, the levels
      of phosphorylated-mitogen-activated protein kinase-activated protein kinase 2 (p
      MK2) were decreased. These results suggested that AhR deficiency resulted in
      increased susceptibility to colitis, whereas activation of AhR by FICZ could
      ameliorate DSS-induced colitis via the MK2/p-MK2/TTP pathway.

PMID- 29207042
TI  - Anti-inflammatory effect of lovastatin is mediated via the modulation of NF
      kappaB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7
      macrophages.
AB  - Lovastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor that is
      clinically used for the prevention of cardiovascular diseases. Although it has
      been reported that lovastatin has anti-inflammatory properties in several
      studies, how lovastatin regulates the inflammation is still unclear. To evaluate
      the effect of lovastatin on nitric oxide production (NO) in RAW264.7 macrophages,
      NO production assay was performed. Also, cell viability was measured to confirm
      cytotoxicity. Level of tumor necrosis factor-alpha (TNF-alpha) transcription was
      measured by reverse transcription polymerase chain reaction (RT-PCR) from total
      RNA in RAW264.7 cells. Western blot analysis and immunofluorescence staining were
      used to investigate the regulation of lovastatin on the expression,
      phosphorylation, and nuclear translocation of cellular proteins. The results of
      the present study revealed that lovastatin reduced nitric oxide production via
      the reduction of inducible nitric oxide synthase (iNOS) expression in
      lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The mRNA level of
      TNF-alpha was reduced in presence of lovastatin. In addition, lovastatin
      downregulated histone deacetylase 1 (HDAC1), resulting in the accumulation of
      acetylated histone H3 and heat shock protein 70. Furthermore, the expression of
      phosphoinositide 3-kinase catalytic subunits alpha and beta was reduced under
      lovastatin treatment, and the phosphorylation of Akt and mammalian target of
      rapamycin was consequently inhibited. Lovastatin also inhibited the
      phosphorylation of inhibitor of nuclear factor (NF)-kappaBalpha and the
      translocation of NF-kappaB into the nucleus. Therefore, the present study
      demonstrates that lovastatin inhibits the expression of pro-inflammatory
      mediators, including iNOS and TNF-alpha, through the suppression of HDAC1
      expression, PI3K/Akt phosphorylation and NF-kappaB translocation in LPS
      stimulated RAW264.7 macrophage cells.

PMID- 29207043
TI  - Naringenin induces laxative effects by upregulating the expression levels of c
      Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced
      constipation.
AB  - Constipation is a common affliction which causes discomfort and affects the
      quality of life of affected individuals. Naringenin (NAR), a natural flavonoid
      widely found in citrus fruits and tomatoes, has been reported to exhibit various
      pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti
      mutagenic, hepatoprotective and anticancer effects. Increasing evidence has
      indicated that NAR has potential for use in the treatment of constipation. Thus,
      the aim of this study was to evaluate the laxative effects of NAR in mice with
      loperamide-induced (Lop-induced) constipation. The data indicated that NAR
      relieved Lop-induced constipation in mice based on the changes of fecal
      parameters (numbers, weight and water content), the intestinal charcoal transit
      ratio and the histological alteration. ELISA revealed that NAR regulated the
      production levels of gastrointestinal metabolic components, such as motilin
      (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase
      (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of
      enteric nerve-related factors, glial cell line-derived neurotrophic factor
      (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase
      (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by
      western blot analysis and RT-PCR analysis. The results of this study suggest that
      NAR relieves Lop-induced constipation by increasing the levels of interstitial
      cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be
      effective as a candidate in patients suffering from lifestyle-induced
      constipation.

PMID- 29207044
TI  - Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear
      factor-kappaB pathway and inhibition of inflammasome activation in alcoholic
      hepatitis.
AB  - Ginsenoside Rg1 (G-Rg1) is an active ingredient of Panax ginseng, which has
      previously been reported to attenuate alcohol-induced hepatic damage; however,
      the underlying mechanisms remain largely unknown. The present study aimed to
      investigate the protective effects of G-Rg1 on alcohol-induced cell injury in
      vitro and on a rat model of alcoholic hepatitis in vivo. For the in vitro model,
      L-O2 cells were incubated with ethanol in the presence or absence of G-Rg1. For
      the in vivo model, rats were administered ethanol by intragastric injection and
      were treated with G-Rg1, or dexamethasone as a control. The results indicated
      that serum biochemical parameters, including alanine aminotransferase, aspartate
      aminotransferase and total bilirubin, as well as the expression of nuclear factor
      (NF)-kappaB pathway-associated inflammatory cytokines, including interleukin (IL)
      6, tumor necrosis factor-alpha and IL-1beta, were elevated in response to
      alcohol; however, they were significantly decreased by G-Rg1 treatment.
      Furthermore, NF-kappaB pathway activation was reduced by treatment with G-Rg1. G
      Rg1 also decreased oxidative stress by inhibiting cytochrome P450 2E1 expression
      and reactive oxygen species production, and promoting glutathione peroxidase
      expression. Furthermore, G-Rg1 inhibited the expression levels of caspase-3 and 
      8, which may be associated with decreased hepatocyte apoptosis. These data
      suggested that G-Rg1 may protect hepatocytes against alcohol-induced injury,
      through preventing excessive inflammation and hepatocellular apoptosis.

PMID- 29207045
TI  - Effect of Atractylodes macrocephala rhizoma on isoproterenol-induced ventricular
      remodeling in rats.
AB  - Myocardial infarction (MI) is the primary cause of ventricular remodeling (VR).
      The aim of the present study was to determine the effect of Atractylodis
      macrocephalae rhizoma (AMR) on VR induced by isoproterenol (ISO) in rats. Male
      Sprague Dawley rats were randomly divided into the normal control, ISO-induced
      and AMR groups. Rats in the ISO-induced and AMR groups were subcutaneously
      injected with 85 mg/kg/day ISO for two consecutive days. Compared with the ISO
      induced group, AMR normalized the levels of hemodynamic parameters, markedly
      attenuated myocardial pathological damage, decreased the level of N-terminal
      prohormone of brain natriuretic peptide, and inhibited cardiac hypertrophy and
      myocardial fibrosis. In addition, AMR inhibited oxidative stress and activation
      of the rennin-angiotensin-aldosterone system (RAAS) when compared with the ISO
      induced group. The results of the present study suggest that AMR may reverse VR
      via its antioxidative effect and inhibition of RAAS activation.

PMID- 29207046
TI  - Nano-sized titanium alloy particles inhibit the proliferation and promote the
      apoptosis of bone marrow mesenchymal stem cells in vitro.
AB  - Aseptic loosening of artificial joints is the leading cause of failure for
      patients who receive total joint arthroplasty. Prior reports indicate that bone
      marrow mesenchymal stem cells (BSMC) are critical in the stabilization of
      implanted artificial joints, and that deregulated interaction between BMSCs and
      artificial joint derived particles is a risk factor for aseptic loosening with an
      unknown mechanism. In the present study, the pathomechanisms whereby titanium and
      its alloy derived particles facilitate aseptic loosing were investigated in
      vitro. It was demonstrated that nano-sized titanium alloy particles significantly
      inhibited the proliferation of BMSCs in a time and concentration dependent
      manner. Furthermore, it was demonstrated that the particles promoted the
      apoptosis of BMSCs in the same manner. Bax and Caspase-3 expression of BMSCs were
      elevated when cultured with the particles. As BMSCs exhibit a critical role in
      the stabilization of artificial joints, the results of the present study may
      provide a novel direction for the management of aseptic loosening in clinics.

PMID- 29207047
TI  - Clinical and next-generation sequencing findings in a Chinese family exhibiting
      severe familial exudative vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is a rare hereditary retinal disorder
      characterized by the premature arrest of vascularization in the peripheral
      retina. The aim of the present study was to characterize the clinical
      presentations of a Chinese family affected by bilateral severe FEVR, and to
      identify the underlying genetic variations. One family that presented with
      bilateral FEVR was recruited for this study. Comprehensive ophthalmic
      examinations, including best-corrected visual acuity, slit-lamp examination,
      fundus photography, fundus fluorescein angiography imaging and electroretinogram
      were performed. Genomic DNA was extracted from leukocytes of the peripheral blood
      collected from the affected and unaffected family members, as well as 200
      unrelated control subjects from the same population. Next-generation sequencing
      of the candidate genes associated with ocular diseases was performed, and the
      identified mutations were validated by conventional polymerase chain reaction
      based sequencing. The functional effects of the mutations were analyzed by
      polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT).
      One heterozygous ATP binding cassette subfamily A member 4 (ABCA4) c.5693G>A
      (p.R1898H) mutation in exon 40 and one heterozygous LDL receptor related protein
      5 (LRP5) c.260T>G (p.I87S) mutation in exon 2 were identified in this family. To
      the best of our knowledge, the ABCA4 c.5693G>A (p.R1898H) mutation has not been
      reported in FEVR, and the LRP5 c.260T>G (p.I87S) mutation is a novel mutation.
      PolyPhen and SIFT predicted that the amino acid substitution R1898H in protein
      ABCA4 is benign, whereas the amino acid substitution I87S in protein LRP5 is
      damaging. A single nucleotide polymorphism c.266A>G (p.Q89R, rs41494349) was
      identified in exon 2 of LRP5. These findings expand the mutation spectrums of
      ABCA4 and LRP5, and will be valuable for genetic counseling and development of
      therapeutic interventions for patients with FEVR.

PMID- 29207048
TI  - TLR4 promotes the expression of HIF-1alpha by triggering reactive oxygen species
      in cervical cancer cells in vitro-implications for therapeutic intervention.
AB  - The present study investigated the mechanism underlying Toll-like receptor 4
      (TLR4)-mediated stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha)
      activity and its association with reactive oxygen species (ROS) in cervical
      cancer cells. SiHa cells were cultured and randomized to control,
      lipopolysaccharide (LPS), methyl-beta-cyclodextrin (MbetaCD)+LPS, ammonium
      pyrrolidinedithiocarbamate (PDTC)+LPS, ST2825+LPS and small interfering (si) RNA
      TLR4+LPS treatment groups. Cell proliferation was quantified using an MTT assay,
      cell cloning was performed using soft agar colony formation and HIF-1alpha
      expression was detected by immunocytochemical staining and western blot analyses.
      Dichloro-dihydro-fluorescein diacetate and lucigenin luminescence assays were
      used to detect alterations in ROS and nicotinamide-adenine dinucleotide phosphate
      (NADPH) oxidase content, respectively. Co-localization of TLR4 and HIF-1alpha was
      detected by immunofluorescence staining and observed using fluorescence
      microscopy. Compared with the control group, cell proliferation was enhanced in
      the LPS-treated group and was not altered in the PDTC+LPS treatment group. Cell
      proliferation was reduced in all other treatment groups (P<0.05). Compared with
      the LPS group, cell proliferation decreased in all other groups. Compared with
      the PDTC+LPS treatment group, cell proliferation significantly decreased when LPS
      was co-administered with ST2825, siTLR4 and MbetaCD (P<0.01). Treatment with
      MbetaCD+LPS exhibited an increased inhibitory effect on cell activity and
      proliferation. Compared with the control group, HIF-1alpha expression was
      enhanced following treatment with LPS, although it decreased when LPS was co
      administered with ST2825, siTLR4 and MbetaCD (P<0.05). HIF-1alpha expression
      decreased following treatment with ST2825, siTLR4, MbetaCD and PDTC+LPS, compared
      with treatment with LPS alone. Compared with the PDTC+LPS group, HIF-1alpha
      activity decreased when LPS was co-administered with ST2825, siTLR4 and MbetaCD.
      NADPH oxidase and ROS levels increased in cells treated with LPS, compared with
      the control group, at 24 and 12 h following treatment, respectively, and
      decreased at 12 h when LPS was co-administered with ST2825, siTLR4 and MbetaCD.
      There was no difference between the LPS and PDTC+LPS groups with respect to NADPH
      and ROS levels. Compared with the PDTC+LPS group, NADPH oxidase activity and ROS
      content decreased when LPS was co-administered with ST2825, siTLR4 and MbetaCD.
      NADPH oxidase activity and ROS content were lowest in the MbetaCD+LPS treatment
      group, and immunofluorescent staining demonstrated that TLR4 was localized to the
      cell surface and HIF-1alpha was primarily localized to the cytoplasm. TLR4 was co
      expressed with HIF-1alpha in cervical cancer cells. The results of the present
      study suggested that TLR4 signaling primarily promoted HIF-1alpha activity via
      activation of lipid rafts/NADPH oxidase redox signaling and may be associated
      with the initiation and progression of cervical cancer. This promoting effect was
      stronger in TLR4/lipid rafts/NADPH oxidase pathway than that in TLR4-NF-kappaB
      signaling pathway. Therefore, the TLR4/lipid raft-associated redox signal may be
      a target for therapeutic intervention to prevent the growth of cervical cancer.

PMID- 29207049
TI  - Coordinated microRNA/mRNA expression profiles reveal a putative mechanism of
      corneal epithelial cell transdifferentiation from skin epidermal stem cells.
AB  - Skin epidermal stem cells (SESCs), which share a single origin with corneal
      epithelial cells (CECs), are considered to be one of the most ideal seed cells
      for the construction of tissue engineered corneas. However, the mechanism
      underlying the transdifferentiation of SESCs to CECs has not been fully
      elucidated. In the present study, to identify critical microRNAs (miRNAs/miRs)
      and genes that regulate the transdifferentiation of SESCs to CECs, SESCs and CECs
      were collected from sheep and used for small RNA sequencing and mRNA microarray
      analyses. Among the differentially expressed miRNAs and genes, 36 miRNAs were
      downregulated and 123 genes were upregulated in the CECs compared with those in
      the SESCs. miR-10b exhibited the largest change in expression between the cell
      types. Target genes of the 36 downregulated miRNAs were predicted and a
      computational approach demonstrated that these target genes may be involved in
      several signaling pathways, including the 'PI3K signaling pathway', the 'Wnt
      signaling pathway' and the 'MAPK signaling pathway', as well as in 'focal
      adhesion'. Comparison of these target genes to the 123 upregulated genes
      identified 43 intersection genes. A regulatory network of these 43 intersection
      genes and its correlative miRNAs were constructed, and three genes (dedicator of
      cytokinesis 9, neuronal differentiation 1 and activated leukocyte cell adhesion
      molecule) were found to have high interaction frequencies. The expression levels
      of 7 randomly selected miRNAs and the 3 intersection genes were further validated
      by reverse transcription-quantitative polymerase chain reaction. It was found
      that miR-10b, the Wnt signaling pathway and the 3 intersection genes may act
      together and serve a critical role in the transdifferentiation process. This
      study identified miRNAs and genes that were expressed in SESCs and CECs that may
      assist in uncovering its underlying molecular mechanism, as well as promote
      corneal tissue engineering using epidermal stem cells for clinical applications.

PMID- 29207050
TI  - In vitro cell behaviors of bone mesenchymal stem cells derived from normal and
      postmenopausal osteoporotic rats.
AB  - Postmenopausal osteoporosis (PMO) increases bone fragility and the risk of
      fractures, and impairs the healing procedure of bone defects in aged women. The
      stromal cell-derived factor-1alpha (SDF-1alpha)/CXC chemokine receptor type 4
      (CXCR4) axis helps to maintain the biological and physiological functions of bone
      marrow mesenchymal stem cells (BMSCs) and increase the homing efficiency of
      BMSCs. The present study aimed to provide insights into the possible association
      between migration and osteogenic ability and the SDF-1alpha/CXCR4 axis in BMSCs
      derived from a rat model of PMO. In order to do this, the general and SDF
      1alpha/CXCR4-associated biological characteristics as well as associated
      molecular mechanisms in BMSCs isolated from a PMO rat model (OVX-BMSCs) and
      normal rats (Sham-BMSCs) were investigated and compared. In comparison with Sham
      BMSCs, OVX-BMSCs exhibited an impaired osteo-genic ability, but a stronger
      adipogenic activity as well as a higher proliferative ability. In addition, OVX
      BMSCs presented a lower chemotactic activity towards SDF-1alpha, lower expression
      levels of CXCR4 and reduced levels of phosphorylated AKT (p-AKT). Therefore, the
      lower expression levels of CXCR4 and p-AKT may be responsible for the impaired
      osteogenic ability and lower chemotactic activity towards SDF-1alpha of OVX
      BMSCs.

PMID- 29207051
TI  - Chlorogenic acid attenuates hydrogen peroxide-induced oxidative stress in lens
      epithelial cells.
AB  - Oxidative stress has an important role in the degradation, oxidation, cross
      linking and aggregation of lens proteins, and can trigger lens epithelial cell
      apoptosis. To investigate the protective effect of chlorogenic acid (CGA) against
      hydrogen peroxide (H2O2)-induced oxidative stress, human lens epithelial cells
      (hLECs) were exposed to various concentrations of H2O2 in the presence and
      absence of CGA. Using MTT assay, reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) and ELISA techniques, cell viability, and protein/mRNA
      levels of BCL2 apoptosis regulator (Bcl-2) and BCL2 associated X apoptosis
      regulator (Bax) were investigated. Additionally, the levels of intracellular
      reactive oxygen species (ROS) and apoptosis within cells were measured using flow
      cytometry to determine the protective effect of CGA on H2O2-induced oxidative
      stress. Furthermore, the protective effect of CGA on H2O2-induced apoptosis was
      also examined using rabbit lenses ex vivo. The results indicated that CGA reduced
      H2O2-induced cytotoxicity in a dose-dependent manner. Flow cytometry analysis
      demonstrated that simultaneous exposure of hLECs to H2O2 and CGA significantly
      decreased apoptosis and the levels of ROS. RT-qPCR analysis revealed a decrease
      in Bcl-2 and an increase in Bax in hLECs following exposure to H2O2 for 24 h,
      regardless of CGA presence. Furthermore, ELISA results indicate that CGA
      increased Bcl-2 expression and decreased Bax expression following treatment with
      H2O2 for 24 h and the Bax/Bcl-2 ratio was significantly decreased by CGA
      treatment. Lens organ culture experiments indicated a dose-dependent decrease in
      H2O2-induced lens opacity following CGA treatment. These results suggest that CGA
      suppresses hLECs apoptosis and prevents lens opacity induced by H2O2 via Bax/Bcl
      2 signaling pathway. CGA may provide effective defenses against oxidative stress
      and, thus, hasigma potential as treatment for a variety of diseases in clinical
      practice.

PMID- 29207052
TI  - Molecular expression of multiple Nav1.5 splice variants in the frontal lobe of
      the human brain.
AB  - Voltage-gated sodium channels serve an essential role in the initiation and
      propagation of action potentials for central neurons. Previous studies have
      demonstrated that two novel variants of Nav1.5, designated Nav1.5e and Nav1.5f,
      were expressed in the human brain cortex. To date, nine distinct sodium channel
      isoforms of Nav1.5 have been identified. In the present study, the expression of
      Nav1.5 splice variants in the frontal lobe of the human brain cortex was
      systematically investigated. The results demonstrated that wild Nav1.5 and its
      splice variants, Nav1.5c and Nav1.5e, were expressed in the frontal lobe of the
      human brain cortex. Nav1.5a, Nav1.5b and Nav1.5d splice variants were not
      detected. However, the expression level of different Nav1.5 variants was revealed
      to vary. The expression ratio of wild Nav1.5 vs. Nav1.5c and Nav1.5e was
      approximately 5:1 and 1:5, respectively. Immunochemistry results revealed that
      Nav1.5 immunoreactivity was predominantly in neuronal cell bodies and processes,
      including axons and dendrites, whereas little immunoreactivity was detected in
      the glial components. These results revealed that a minimum of four Nav1.5 splice
      variants are expressed in the frontal lobe of the human brain cortex. This
      indicates that the previously reported tetrodotoxin-resistant sodium current was
      a compound product of different Nav1.5 variants. The present study revealed that
      Nav1.5 channels have a more abundant expression in the human brain than
      previously considered. It also provided further insight into the complexity and
      functional significance of Nav1.5 channels in human brain neurons.

PMID- 29207053
TI  - Diagnostic significance and potential function of miR-338-5p in hepatocellular
      carcinoma: A bioinformatics study with microarray and RNA sequencing data.
AB  - MicroRNA (miR)-338-5p has been studied in hepatocellular carcinoma (HCC);
      however, the diagnostic value and molecular mechanism underlying its actions
      remains to be elucidated. The present study aimed to validate the diagnostic
      ability of miR-338-5p and further explore the underlying molecular mechanism.
      Data from eligible studies, Gene Expression Omnibus (GEO) chips and The Cancer
      Genome Atlas (TCGA) datasets were gathered in the data mining and the integrated
      meta-analysis, to evaluate the significance of miR-338-5p in diagnosing HCC
      comprehensively. The potential target genes of miR-338-5p were achieved from the
      intersection of the deregulated targets of miR-338-5p from GEO and TCGA in
      addition to the predicted target genes from 12 online software. A protein-protein
      interaction (PPI) network was drawn to illustrate the interaction between target
      genes and to define the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway enrichment analyses were performed to
      investigate the function of the target genes. From the results, miR-338-5p
      exhibited favorable value in diagnosing HCC. Types of sample and experiment were
      defined as the possible sources of heterogeneity in meta-analysis. A total of 423
      genes were selected as the potential target genes of miR-338-5p, and five genes
      were defined as the hub genes from the PPI network. The GO and KEGG analyses
      indicated that the target genes were significantly assembled in the pathways of
      metabolic process and cell cycle. miR-338-5p may function as a novel diagnostic
      target for HCC through regulating certain target genes and signaling pathways.

PMID- 29207054
TI  - Use of methylation profiling to identify significant differentially methylated
      genes in bone marrow mesenchymal stromal cells from acute myeloid leukemia.
AB  - The present study aimed to characterize the epigenetic architecture by studying
      the DNA methylation signature in bone marrow mesenchymal stem cells (BM-MSCs)
      from patients with acute myeloid leukemia (AML). Microarray dataset GSE79695 was
      downloaded from the Gene Expression Omnibus database. Differentially methylated
      sites and differentially methylated CpG islands were identified in BM-MSC samples
      from patients with AML compared with controls. MicroRNAs (miRs) encoding genes
      covering differentially methylated sites were found and the regulation network
      was constructed. Pathway enrichment analysis of hypermethylated genes and
      hypomethylated genes was performed, followed by protein-protein interaction (PPI)
      network construction. Moreover, the identified differentially methylated genes
      were compared with the leukemia-related marker/therapeutic genes from the
      literature. Overall, 228 hypermethylated CpG site probes covering 183 gene
      symbols and 523 hypomethylated CpG sites probes covering 362 gene symbols were
      identified in the BM-MSCs from AML patients. Furthermore, 4 genes with CpG island
      hypermethylation were identified, including peptidase M20 domain containing 1
      (PM20D1). The hsa-miR-596-encoding gene MIR596 was found to be hypermethylated
      and the regulation network based on hsa-miR-596 and its targets (such as
      cytochrome P450 family 1 subfamily B member 1) was constructed. Hypermethylated
      and hypomethylated genes were enriched in different Kyoto Encyclopedia of Genes
      and Genomes pathways, including 'hsa05221: Acute myeloid leukemia' and 'hsa05220:
      Chronic myeloid leukemia', which the hypomethylated gene mitogen-activated
      protein kinase 3 (MAPK3) was involved in. In addition, MAPK3, lysine demethylase
      2B and RAP1A, member of RAS oncogene family were hubs in the PPI network of
      methylated genes. In conclusion, PM20D1 with hypermethylation of CpG islands may
      be associated with the energy expenditure of patients with AML. Furthermore, the
      aberrantly hypermethylated miR-159-encoding gene MIR159 may be a potential
      biomarker of AML.

PMID- 29207055
TI  - Therapeutic effects of conditioned medium from bone marrow-derived mesenchymal
      stem cells on epithelial-mesenchymal transition in A549 cells.
AB  - Pulmonary fibrosis (PF) is a chronic lung disease. The transforming growth factor
      beta1 (TGF-beta1)/Smad3 signaling pathway plays an important role in the
      pathogenesis of pulmonary fibrosis. Bone marrow-derived mesenchymal stem cells
      (BMSCs) have been shown to be a modulator of the molecular aspects of the
      fibrosis pathway. However, it is still unknown as to whether the conditioned
      medium from BMSCs (BMSCs-CM) inhibits the epithelial-mesenchymal transition (EMT)
      process. This study confirmed the hypothesis that BMSCs-CM exerts an anti
      fibrotic effect on human type II alveolar epithelial cells (A549) by suppressing
      the phosphorylation of Smad3. We used the A549 cells in vitro to detect
      morphological evidence of EMT by phase-contrast microscopy. These cells were
      randomly divided into 4 groups as follows: the control group, the TGF-beta1
      group, the SIS3 (specific inhibitor of Smad3) group and the BMSCs-CM group. The
      immunofluorescence method was used to determined the location of E-cadherin (E
      calcium mucins; E-cad), alpha-smooth muscle actin (alpha-SMA) and p-Smad3. The
      expression levels of E-cad, CK8, alpha-SMA, vimentin, p-Smad3, Snail1, collagen I
      (COLI) and collagen III (COLIII) were detected by western blot analysis.
      Following exposure to TGF-beta1, the A549 cells displayed a spindle-shaped
      fibroblast-like morphology. In accordance with these morphological changes, the
      expression levels of E-cad and CK8 were downregulated, while the expression
      levels of alpha-SMA and vimentin were upregulated. Along with this process, the
      expression levels of p-Smad3, Snail1, COLI and COLIII were increased. However,
      the cells in the BMSCs-CM group and SIS3 group exhibited a decrease in the levels
      of alpha-SMA and vimentin (which had been upregulated by TGF-beta1), and an
      increase in the levels of E-cad and CK8 expression (which had been downregulated
      by TGF-beta1). On the whole, these results indicated that BMSCs-CM suppressed the
      EMT which might be associated with TGF-beta1/Smad3. This study provides the
      theoretical basis for the research of the mechanisms responsible for pulmonary
      disease.

PMID- 29207056
TI  - Different roles of Akt and mechanistic target of rapamycin in serum-dependent
      chondroprotection of human osteoarthritic chondrocytes.
AB  - Despite various animal serums being used widely to culture chondrocytes, the
      regulatory mechanism of serum on chondrocyte activities has not been elucidated.
      In the present study, human osteoarthritis (OA) chondrocytes were used to perform
      in vitro investigations on the effect of different concentrations of bovine fetal
      serum on extracellular matrix synthesis, cell proliferation and autophagy using
      the Cell Counting Kit-8 analysis, a laser-scanning confocal microscope, and
      western blot analysis. The results demonstrated that 5% serum exerted a
      chondroprotective effect more than the other concentrations of serum, as it
      simultaneously promoted cell proliferation, autophagy, and ECM synthesis in human
      OA chondrocytes. Furthermore, the decreased mechanistic target of rapamycin
      (mTOR) and increased Akt were observed in 5% serum-treated OA chondrocytes.
      Either mTOR or Akt inhibitor influenced the effect of 5% serum on cell
      proliferation and autophagy in human OA chondrocytes, which was associated with
      LC-3B or B-cell lymphoma-2 (Bcl-2) signal molecules. Consistent with previous
      studies, the present study proposes that 5% serum promotes cell proliferation via
      the Akt/Bcl-2 axis and induces autophagy via the mTOR/LC-3B axis in human OA
      chondrocytes. Furthermore, the different roles of Akt and mTOR in the cell
      processes of human OA chondrocytes require consideration for preclinical and
      clinical therapy of OA.

PMID- 29207057
TI  - Molecular mechanism and targeted therapy of Hsp90 involved in lung cancer: New
      discoveries and developments (Review).
AB  - The exploration of the molecular mechanisms and signaling pathways on lung cancer
      is very important for developing new strategies of diagnosis and treatment to
      this disease, such as finding valuable lung cancer markers and molecularly
      targeted therapies. Previously, a number of studies disclose that heat shock
      protein 90 (Hsp90) is upregulated in cancer cells, tissues and serum of lung
      cancer patients, and its upregulation intimately correlates with the occurrence,
      development and outcome of lung cancer. On the contrary, inhibition of Hsp90 can
      suppress cell proliferation, motility and metastasis of lung cancer and promote
      apoptosis of lung cancer cells via complex signaling pathways. In addition, a
      series of Hsp90 inhibitors have been investigated as effective molecular targeted
      therapy tactics fighting against lung cancer. This review, systematically
      summarizes the role of Hsp90 in lung cancer, the molecular mechanisms and
      development of anti-Hsp90 treatment in lung cancer.

PMID- 29207058
TI  - Protective effect of baicalin against severe burn-induced remote acute lung
      injury in rats.
AB  - Baicalin exhibits antibacterial, anti-viral, anti-oxidative, antipyretic,
      analgesic, anti-inflammatory and anti-tumor properties. The chemical scavenges
      oxygen free radicals, protects the cardiovascular system and neurons, protects
      the liver, and has been used for the prevention and treatment of diabetes
      associated complications. The present study investigated the effect of baicalin
      on severe burn-induced remote acute lung injury (ALI). The present study
      demonstrated that baicalin significantly decreased the lung wet-to-dry weight
      ratio, improved pulmonary histological alterations and reduced the expression of
      high mobility group protein B1 in the rat model of ALI. In addition, treatment
      with baicalin decreased tumor necrosis factor-alpha, interleukin (IL)-8, IL-1beta
      and IL-18 concentrations in the serum, reduced myeloperoxidase activity and
      malondialdehyde content, and increased the level of superoxide dismutase in the
      serum in treated model rats with ALI. As a result, baicalin significantly
      suppressed nucleotide-binding oligomerization, NACHT, LRR and PYD domains
      containing protein 3 (NLRP3), caspase-1, nuclear factor-kappaB and matrix
      metalloproteinase-9 protein expression in the rat model of ALI. The results of
      the present study suggested that baicalin may serve a protective role against ALI
      in rats through the NLRP3 signaling pathway.

PMID- 29207059
TI  - Therapeutic effect of adipose-derived stem cell transplantation on optic nerve
      injury in rats.
AB  - Adipose-derived stem cells (ADSCs) are mesenchymal stem cells in adipose tissue.
      ADSCs may differentiate into cells and tissues of different embryonic germ layers
      under specific inducing conditions. Previous studies have demonstrated that
      Schwann cells transformed from ADSCs can express nerve growth factors, generate
      nerve fibers and promote axonal regeneration in models of peripheral nerve
      injury. Stem cell transplantation is one of the potential techniques for the
      treatment of retinal ganglion cell injury. The present study developed an optic
      nerve crush injury rat model to investigate the therapeutic effect of fat stem
      cell transplantation on optic nerve injured rats. Retinal morphological changes
      were observed on day 3, 7, 14, 21 and 28 following optic nerve injury. It was
      determined that the number of retinal ganglion cells (RGCs) decreased with time
      following optic nerve injury; however, the number of RGCs in the stem cell
      transplantation group was higher compared with the buffer control group. The
      results of reverse transcription-quantitative polymerase chain reaction also
      demonstrated that the growth associated protein 43 mRNA expression level of the
      stem cell transplantation group was higher compared with the buffer control
      group. Apoptosis tests demonstrated that the stem cell transplantation group was
      able to resist the apoptosis of retinal cells. The present study demonstrated
      that in vivo transplantation of ADSCs can improve the survival rate of RGCs in
      rats with optic nerve injury and to resist the apoptosis of retinal cells.

PMID- 29207060
TI  - Honokiol induces autophagy and apoptosis of osteosarcoma through PI3K/Akt/mTOR
      signaling pathway.
AB  - Honokiol is the main active constituent of Magnolia officinalis. With effective
      and long-term pharmacological functions of being antibacterial, anti-oxidative,
      anti-inflammatory, antitumor, anti-spasmic, anti-anxiety and anti-viral, Honokiol
      is clinically used in the treatment of acute enteritis and chronic gastritis. The
      aim of the present study was to observe the possible anti-effects of honokiol on
      autophagy and apoptosis of osteosarcoma, and to investigate the role of the
      PI3K/Akt/mTOR signaling pathway in its anticancer effects. MTT assay was used to
      evaluate cell proliferation and Annexin V-fluorescein isothiocyanate/propidium
      iodide staining flow cytometry was used to analyze the apoptotic rate. The
      authors identified that honokiol could inhibit cell proliferation and induce the
      apoptotic rate of osteosarcoma cells. The expression level of Bcl-2-like protein
      4, caspase-3 and p53 protein expression were induced and cyclin D1 protein
      expression was suppressed in osteosarcoma cells by honokiol. Autophagy-associated
      LC3II protein expression level was promoted, and PI3K, p-Akt and p-mTOR protein
      expression level was suppressed in osteosarcoma cells by honokiol. The present
      study demonstrated, to the best of the authors' knowledge, for the first time
      that honokiol induces autophagy and apoptosis of osteosarcoma cells through the
      PI3K/Akt/mTOR signaling pathway.

PMID- 29207061
TI  - Neurochemical changes in the hippocampus and prefrontal cortex associated with
      electroacupuncture for learning and memory impairment.
AB  - Electroacupuncture (EA) has been widely used to treat cognitive impairment
      following cerebral ischemia. However, the functional mechanisms of EA have not
      been fully elucidated. The aim of the present study was to investigate whether EA
      at the GV 20 and DU 24 acupoints can improve the learning and memory ability via
      alteration of the neurochemical metabolism in the hippocampus (HPC) and
      prefrontal cortex (PFC) of rats with ischemia and reperfusion (I/R) injury.
      Sprague-Dawley male rats were randomly divided into three groups, namely the sham
      group (n=12), the middle cerebral artery occlusion (MCAO) group (n=12) and the EA
      treatment (MCAO + EA) group (n=12). MCAO was performed to establish the left
      focal cerebral I/R injury model, and the GV 20 and DU 24 acupoints were then
      stimulated with EA for 30 min per time, once daily, for 7 consecutive days. The
      Morris water maze (MWM) test was used to assess learning and memory ability. T2
      weighted imaging was used to assess the cerebral infarct volume. Magnetic
      resonance spectroscopy was used to assess neurochemical metabolism of HPC and
      PFC. The neurological scores of the MCAO + EA group were significantly reduced
      compared with those of the MCAO group 7 days after EA treatment (P<0.01). The
      escape latency of the MWM test in the MCAO + EA group was found to be shorter
      compared with that in the MCAO group (P<0.01). The number of rats crossing
      through the platform area was significantly higher in the MCAO + EA group
      compared with that in the MCAO group (P<0.01). The cerebral infarct volume was
      also decreased in the MCAO + EA group compared with the MCAO group (P<0.05). The
      ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr of left-to
      right HPC were increased in the MCAO + EA group compared with the MCAO group;
      however, the ratio of glutamate (Glu)/Cr did not change significantly (P>0.05).
      The ratios of NAA/Cr, Cho/Cr and Glu/Cr of left-to-right PFC were elevated
      (P<0.05). In conclusion, EA at the GV 20 and DU 24 acupoints may ameliorate
      learning and memory ability, possibly through increasing the levels of NAA and
      Cho in the HPC and PFC of rats with I/R injury.

PMID- 29207062
TI  - Sevoflurane inhibits the malignant potential of head and neck squamous cell
      carcinoma via activating the hypoxia-inducible factor-1alpha signaling pathway in
      vitro.
AB  - Sevoflurane, an inhalational anesthetic, is extensively used during oral cancer
      surgery. However, the effect of sevoflurane on head and neck squamous cell
      carcinoma (HNSCC) remains unclear. The objective of the present study was to
      investigate the effects of sevoflurane on the proliferation, apoptosis and
      invasion in HNSCC cell lines and the underlying molecular mechanism. The Cell
      Counting Kit-8 assay was used to evaluate cell proliferation. Apoptosis was
      analyzed by flow cytometry. Cell invasion was evaluated using the Transwell
      invasion assay. The expression levels of Akt, p-Akt (Ser473), hypoxia-inducible
      factor-1alpha (HIF-1alpha), Fas and Bcl-2 were measured by western blotting.
      Significant inhibition of cell proliferation and induction of apoptosis were
      observed in FaDu and CAL-27 cells following sevoflurane treatment. The expression
      of Akt, p-Akt (Ser473) and Bcl-2 was supressed, while that of Fas was
      significantly increased, which was partly associated with the activation of the
      HIF-1alpha pathway. In addition, the results revealed a statistically significant
      inhibition of cell invasion in the FaDu cell line following exposure to 2 and 4%
      sevoflurane for 2, 4, 6 and 8 h. Therefore, the present study demonstrated that
      sevoflurane decreased the malignant behavior of HNSCC cell lines in vitro, which
      was associated with activation of the HIF-1alpha pathway.

PMID- 29207063
TI  - Forskolin attenuates retinal inflammation in diabetic mice.
AB  - The present study aimed to investigate the effect of forskolin on retinal
      inflammation under diabetic conditions. C57BL/6 mice were randomly divided into
      normal control, diabetic control and forskolin treatment groups. The diabetic
      model was established by intraperitoneal injection of streptozotocin. The
      forskolin treatment group received intragastrical administration of forskolin for
      12 weeks, the other two groups received an equal amount of PBS. At 21 weeks
      following diabetic induction, an immunoblotting test was conducted to investigate
      the expression of two inflammatory factors: Intercellular adhesion molecule-1
      (ICAM-1) and tumor necrosis factor-alpha (TNF-alpha). Glucose concentration was
      additionally calculated. A leukostasis assay was utilized to compare
      microvasculature pathological alterations. It was demonstrated that retinal
      glucose concentration of diabetic control and forskolin treatment were both
      increased compared with normal control, however the forskolin treatment group was
      only ~68.06% of the diabetic control due to downregulated glucose transporter 1
      expression. The expression of ICAM-1 and TNF-alpha were upregulated in the
      forskolin treatment and diabetic control groups compared with the normal control,
      however these two inflammatory factor expression levels in the forskolin
      treatment group were ~68.75 and 75.37% of diabetic control. It was additionally
      observed that there were less adherent leukocytes in retinal microvasculature in
      the forskolin treatment group compared with diabetic control. All the differences
      observed were significant. Overall, by means of limiting glucose transport into
      the retina via forskolin, the retinal environment with lower glucose
      concentration alleviates the inflammatory response under diabetic conditions.

PMID- 29207064
TI  - Quinalizarin exerts an anti-tumour effect on lung cancer A549 cells by modulating
      the Akt, MAPK, STAT3 and p53 signalling pathways.
AB  - Quinalizarin may be a potential chemical agent for cancer therapy, as it exerts
      anti-tumour effects against a variety of different types of cancer. However, the
      underlying regulatory mechanism and signalling pathways of quinalizarin in lung
      cancer cells remains unknown. The present study sought to investigate the effects
      of quinalizarin on proliferation, apoptosis and reactive oxygen species (ROS)
      generation in lung cancer. MTT assays were used to evaluate the effects of
      quinalizarin on the viability of lung cancer A549, NCI-H460 and NCI-H23 cells.
      Flow cytometry was employed to evaluate the effects of quinalizarin on the cell
      cycle, apoptosis and ROS generation in A549 cells. Western blotting was performed
      to detect cell cycle and apoptosis-associated protein expression levels in A549
      cells. Quinalizarin inhibited A549, NCI-H460 and NCI-H23 cell proliferation and
      induced A549 cell cycle arrest at the G0/G1 phase. Quinalizarin induced apoptosis
      by upregulating the expression of B-cell lymphoma 2 (Bcl-2)-associated agonist of
      cell death, cleaved-caspase-3 and cleaved-poly (adenosine diphosphate-ribose)
      polymerase, and downregulating the expression of Bcl-2. Furthermore, quinalizarin
      activated mitogen-activated protein kinase (MAPK) and p53, and inhibited the
      protein kinase B and signal transducer and activator of transcription-3 (STAT3)
      signalling pathways. In addition, quinalizarin increased ROS generation. The ROS
      scavenger N-acetyl-L-cysteine restored quinalizarin-induced cell apoptosis, and
      inactivated the MAPK and STAT3 signalling pathways. The results of the present
      study demonstrated that quinalizarin induces G0/G1 phase cell cycle arrest and
      apoptosis via ROS mediated-MAPK and STAT3 signalling pathways.

PMID- 29207065
TI  - Estrogen inhibits the overgrowth of Escherichia coli in the rat intestine under
      simulated microgravity.
AB  - Microgravity can affect many aspects of intestinal homeostasis, leading to an
      increased risk of colitis. Estrogen, the most frequently affected hormone when
      under simulated microgravity, regulates the permeability of the colonic mucosa
      barrier. The associations between alterations in intestinal microbiota and
      increased susceptibility under microgravity have not been thoroughly elucidated.
      The aim of the present study was to evaluate the changes in intestinal microbiota
      under simulated microgravity and to investigate the protective effect of estrogen
      against those changes. The hindlimb unweighting (HU) model was used to simulate
      microgravity in rats. Estrogen was administered via intramuscular injection.
      Amplicons of the V3 variable regions of bacterial 16S rDNA were analyzed using
      denaturing gradient gel electrophoresis (DGGE), cloning and sequencing. Several
      specific bacterial groups were assayed using quantitative-polymerase chain
      reaction. Bacterial translocation was evaluated by detecting serum
      lipopolysaccharide (LPS) and LPS binding protein (LBP) levels. DGGE profiles
      generated by universal primers revealed minor, though specific, changes in
      bacterial communities under simulated microgravity, particularly the band
      matching the sequence of Escherichia coli (E. coli). The quantification of 16S
      RNA revealed increased numbers of Bacteroides fragilis, E. coli and Fusobacterium
      nucleatum; however, Bifidobacteria longum significantly decreased under
      microgravity. Estrogen inhibited the overgrowth of E. coli, and decreased the
      levels of LBS and LBP under simulated microgravity. These results demonstrated
      that simulated microgravity alters the intestinal microflora and may contribute
      to bacterial translocation in the gut mucosa. The data also suggested that
      further investigations evaluating the administration of estrogen to protect
      against microgravity-associated diseases may be required.

PMID- 29207066
TI  - Erythropoietin induces the osteogenesis of periodontal mesenchymal stem cells
      from healthy and periodontitis sources via activation of the p38 MAPK pathway.
AB  - Erythropoietin (Epo), a hematopoietic hormone, has multiple biological functions.
      Recently, the positively osteogenic effects of Epo on mesenchymal stem cells
      (MSCs) have attracted broad interest. However, the effects of Epo on the
      osteogenesis of human periodontal ligament tissue-derived mesenchymal stem cells
      (hPDLSCs) and periodontitis mesenchymal stem cells (pPDLSCs) from patients with
      periodontitis remain unknown. In the present study, osteogenic effects of Epo on
      hPDLSCs and pPDLSCs were investigated, and the results suggested that the effects
      were mediated by promoting the expression of runt related transcription factor 2,
      alkaline phosphatase (ALP) and osteocalcin. Using Alizarin Red and ALP staining,
      it was demonstrated that Epo exerted positive osteogenic effects on hPDLSCs and
      pPDLSCs. Additionally, Epo upregulated the proliferation of hPDLSCs and pPDLSCs,
      based on flow cytometric analyses of the cell cycle. To determine the underlying
      mechanism, the role of the p38 mitogen-activated protein kinase (MAPK) pathway,
      which is associated with the osteogenesis of hPDLSCs and pPDLSCs, was
      investigated further. Epo increases p38 phosphorylation (the target of the MAPK
      pathway) in hPDLSCs and pPDLSCs. Furthermore, when the cells were treated with
      SB203580, an inhibitor of the p38 MAPK pathway, the osteogenic effects of Epo on
      hPDLSCs and pPDLSCs were attenuated. In conclusion, Epo may upregulate the bone
      formation ability of hPDLSCs and pPDLSCs via the p38 MAPK pathways.

PMID- 29207068
TI  - Role of DDAH/ADMA pathway in TGF-beta1-mediated activation of hepatic stellate
      cells.
AB  - Asymmetric dimethylarginine (ADMA) is catalyzed by the enzyme dimethylarginine
      dimethylaminohydrolase (DDAH) in humans, and the role for ADMA has been
      associated with hepatic fibrogenesis. Transforming growth factor-beta (TGF-beta)
      has been shown to mediate the myofibroblastic transformation of quiescent hepatic
      stellate cells (HSCs), a pivotal step in liver fibrogenesis. However, the
      underlying molecular mechanisms are not well understood. Accumulation of ADMA due
      to low activity of DDAH has been reported to be associated with liver damage and
      hepatic fibrosis. In this study, the role of the DDAH/ADMA pathway in the TGF
      beta1-induced HSC activation was assessed. Freshly harvested primary HSCs from
      rat liver were used in this study. It was demonstrated that TGF-beta1 treatment
      significantly suppressed the DDAH protein expression and activity, and increased
      levels of ADMA in the culture medium of rat primary HSCs. Notably, the TGF-beta1
      mediated effects on DDAH/ADMA were significantly abrogated by the p38 mitogen
      activated protein kinase specific inhibitor, SB203580. Furthermore, it was
      demonstrated that excessive ADMA led to an increase in the number of TGF-beta1
      positive HSCs and induced the expression of alpha-smooth muscle actin and
      collagen type I in rat primary HSCs. In addition, rat primary HSCs exposed to
      excessive ADMA showed a significant increase in the expressions of alpha-SMA and
      collagen type I. Finally, it was revealed that ADMA treatment promoted the
      proliferation of rat primary HSCs. In conclusion, the results obtained from the
      study suggest a potentially novel role for the ADMA/DDAH1 signaling pathway in
      TGF-beta1-induced HSC activation, and along with the studies of others,
      suppression of the ADMA/DDAH1 pathway may be an alterative approach for the
      treatment of liver fibrosis.

PMID- 29207067
TI  - High glucose/lysophosphatidylcholine levels stimulate extracellular matrix
      deposition in diabetic nephropathy via platelet-activating factor receptor.
AB  - Platelet-activating factor (PAF), protein kinase C (PKC)betaI, transforming
      growth factor (TGF)-beta1 and aberrant extracellular matrix (ECM) deposition have
      been associated with diabetic nephropathy (DN). However, the mechanistic basis
      underlying this association remains to be elucidated. The present study
      investigated the association among the aforementioned factors in a DN model
      consisting of human mesangial cells (HMCs) exposed to high glucose (HG) and
      lysophosphatidylcholine (LPC) treatments. HMCs were divided into the following
      treatment groups: Control; PAF; PAF+PKCbetaI inhibitor LY333531; HG + LPC; PAF +
      HG + LPC; and PAF + HG + LPC + LY333531. Cells were cultured for 24 h, and
      PKCbetaI and TGF-beta1 expression was determined using the reverse transcription
      quantitative polymerase chain reaction and western blotting. The expression
      levels of the ECM-associated molecules collagen IV and fibronectin in the
      supernatant were detected using ELISA analysis. Subcellular localization of
      PKCbetaI was assessed using immunocytochemistry. PKCbetaI and TGF-beta1
      expression was increased in the PAF + HG + LPC group compared with the other
      groups (P<0.05); however, this effect was abolished in the presence of LY333531
      (P<0.05). Supernatant fibronectin and collagen IV levels were increased in the
      PAF + HG + LPC group compared with the others (P<0.05); this was reversed by
      treatment with LY333531 (P<0.05). In cells treated with PAF, HG and LPC, PKCbetaI
      was translocated from the cytosol to the nucleus, an effect which was blocked
      when PKCbetaI expression was inhibited (P<0.05). The findings of the present
      study demonstrated that PAF stimulated ECM deposition in HMCs via activation of
      the PKC-TGF-beta1 axis in a DN model.

PMID- 29207069
TI  - Stimulation of chondrocytes and chondroinduced mesenchymal stem cells by
      osteoinduced mesenchymal stem cells under a fluid flow stimulus on an integrated
      microfluidic device.
AB  - The aim of the present study was to investigate the stimulation of osteoinduced
      mesenchymal stem cells (MSCs) into chondrogenically predifferentiated MSCs and
      chondrocytes in a mechanical environment. A novel two-layer microfluidic chip was
      used to mimic the interstitial flow in the superficial zones of articular
      cartilage. The morphology, proliferation rate and the expression of collagen I,
      collagen II and aggrecan of chondrocytes and chondro-MSCs were investigated. The
      results revealed that the cells in the bottom layer were influenced by the top
      layer's osteoinduced MSCs and the bottom layer's shear flow. The expression of
      collagen I, which may signify the effect of the shear stress on the
      dedifferentiation change, was weakened by the stimulation of osteoinduced MSCs on
      the top layer. The expression of collagen II and aggrecan was increased in the
      fluidic environment by osteoinduced MSCs. These results indicate that
      osteoinduced MSCs have a significant effect on the phenotype of chondro-MSCs and
      chondrocytes in the fluidic microenvironment. The present study described a
      simple and promising way to rapidly evaluate cell responses to other cells in a
      fluidic environment, which may help to better promote the utilization of MSCs and
      chondrocytes in tissue engineering.

PMID- 29207070
TI  - KIF9-AS1, LINC01272 and DIO3OS lncRNAs as novel biomarkers for inflammatory bowel
      disease.
AB  - Long non-coding RNAs (lncRNAs) are a novel group of non-coding RNAs that are
      associated with inflammation and tumorigenesis. At present, the diagnostic
      efficacy of lncRNAs in inflammatory bowel disease (IBD) is unclear. The present
      study aimed to identify lncRNAs that may be used as potential biomarkers for IBD.
      The mRNA expression levels of various lncRNAs (KIF9-AS1, LINC01272 and DIO3OS)
      were detected in tissue and plasma samples from patients with IBD by reverse
      transcription-quantitative polymerase chain reaction. The results indicated that
      the mRNA expression levels of KIF9-AS1 and LINC01272 were significantly
      upregulated in tissue and plasma samples from patients with IBD compared with in
      the healthy controls; conversely, the mRNA expression levels of DIO3OS were
      significantly downregulated in tissue and plasma samples from patients with IBD
      compared with in the healthy controls. Subsequently, the specificity and
      sensitivity of KIF9-AS1, LINC01272 and DIO3OS were determined using a receiver
      operating characteristic (ROC) curve analysis. The results indicated that KIF9
      AS1, LINC01272 and DIO3OS had potential diagnostic value for the detection of
      IBD. Furthermore, there were significantly positive correlations in KIF9-AS1,
      LINC01272 and DIO3OS expression between IBD tissue and plasma samples. Therefore,
      the present study indicated that KIF9-AS1, LINC01272 and DIO3OS may be potential
      diagnostic biomarkers for IBD.

PMID- 29207071
TI  - Hepatocellular carcinoma-targeted nanoparticles for cancer therapy.
AB  - Nanocarriers, such as liposomes, have the potential to increase the payload of
      chemotherapeutic drugs while decreasing toxicity to non-target tissues; such
      advantageous properties can be further enhanced through surface conjugation of
      nanocarriers with targeting moieties. We previously reported that SP94 peptides,
      identified by phage display, exhibited higher binding affinity to human
      hepatocellular carcinoma (HCC) than to hepatocytes and other normal cells. Here,
      we confirm the tumor-targeting properties of SP94 peptide by near-infrared
      fluorescence imaging. Non-targeted PEGylated liposomal doxorubicin (LD) and SP94
      conjugated PEGylated liposomal doxorubicin (SP94-LD) were compared by assessing
      pharmacokinetics, tissue distribution, and antitumor efficacy in xenograft
      bearing mice, in order to investigate the effectiveness of SP94-mediated
      targeting for cancer therapy. SP94-LD demonstrated a significant increase in drug
      accumulation in tumors, while its plasma residence time was the same as its non
      targeted equivalent. Consistent with this result, conjugation of targeting
      peptide SP94 enhances the therapeutic efficacy of liposomal doxorubicin in mouse
      models with hepatocellular carcinoma xenografts. Furthermore, combination
      targeted therapy exhibited a significant enhancement against orthotopic tumor
      growth, and markedly extended the survival of mice compared with all other
      treatments. Our study shows that SP94-mediated targeting enhances antitumor
      efficacy by improving tumor pharmacokinetics and tissue distribution, allowing
      large amounts of antitumor drugs to accumulate in tumors.

PMID- 29207072
TI  - Transcription factor TBX18 promotes adult rat bone mesenchymal stem cell
      differentiation to biological pacemaker cells.
AB  - Bone mesenchymal stem cells (BMSCs) are currently considered the optimal stem
      cells for biological pacemaker cell transformation. The cardiac-specific
      transcription factor T-Box protein 18 (TBX18) is essential for sinoatrial node
      (SAN) formation, particularly formation of the head region that generates the
      electrical impulses that induce heart contraction. The present study aimed to
      confirm the effects of TBX18 on biological pacemaker differentiation of rat
      BMSCs. Flow cytometry was used to identify the surface markers of BMSCs, in order
      to acquire pure mesenchymal stem cells. Subsequently, BMSCs were transduced with
      TBX18 or green fluorescent protein adenovirus vectors. The effects of TBX18 were
      evaluated using SAN-specific makers including TBX18, alpha-actin, cardiac
      troponin I, hyperpolarization-activated cyclic nucleotide-gated channel 4 and
      connexin 43 by reverse transcription-quantitative polymerase chain reaction,
      western blotting and immunofluorescence. The findings demonstrated that direct
      conversion of BMSCs to biological pacemaker cells via TBX18 is a feasible method
      in the field of cardiology.

PMID- 29207073
TI  - P2X7 receptor antagonist protects retinal ganglion cells by inhibiting microglial
      activation in a rat chronic ocular hypertension model.
AB  - Microglial activation and the release of pro-inflammatory cytokines occur during
      early glaucoma. However, the exact mechanism underlying the initiation of the
      microglial activation process remains unclear. Thus, the present study
      investigated the potential role of a purine receptor subtype, the P2X
      purinoceptor 7 (P2X7) receptor, during microglial activation in the retinal
      tissues of a rat chronic ocular hypertension (COH) model. This was achieved by
      cauterizing 3 of the 4 episcleral veins. Microglial activation and caspase-1
      upregulation were observed in COH rat retinas by immunohistochemical and western
      blotting techniques. Intravitreal injection of 2',3'-O-(4-benzoylbenzoyl)-ATP
      (BzATP), a P2X7 receptor agonist, induced microglial activation in normal rat
      retinal tissues, which was alleviated by pretreatment with the P2X7 receptor
      antagonist, Brilliant Blue G (BBG). BBG further attenuated caspase-1 increment in
      COH rat retinal tissues. The data demonstrated that BBG reduced TUNEL-positive
      retinal ganglion cells in whole-mount retinal tissues with COH and normal retinal
      tissues following intravitreal injection with BzATP. One may conclude that the
      P2X7 receptor may be involved in microglial activation in the COH retina and
      could be considered a target for neuronal protection in glaucoma.

PMID- 29207074
TI  - Establishment of a novel hepatic steatosis cell model by Cas9/sgRNA-mediated
      DGKtheta gene knockout.
AB  - To investigate the role of diacylglycerol kinase theta (DGKtheta) in lipid
      metabolism and insulin resistance, the present study generated an in vitro
      hepatic steatosis cell model by knockout of the DGKtheta gene in liver cancer
      cell line HepG2 using CRISPR/Cas9 technology. The cell line was characterized by
      Oil Red O staining and shown to exhibit increased intracellular lipid
      accumulation, compared with that in wild-type liver cancer cell line HepG2. The
      gene expression levels of signaling proteins in pathways involved in lipid
      metabolism, insulin resistance and gluconeogenesis were also examined. The
      DGKtheta-knockout HepG2 cells showed increased mRNA and protein expression levels
      of lipid synthesis-related genes, fatty acid synthase, peroxisome proliferator
      activated receptor-gamma and sterol regulatory element-binding protein-1c, and
      decreased expression levels of the lipolysis-related gene, carnitine
      palmitoyltransferase1A. These changes may account for the increased intracellular
      lipid content of this cell line. The DGKtheta-knockout HepG2 cells also exhibited
      an increased phosphorylation level of protein kinase Cepsilon and decreased
      phosphorylation levels of insulin receptor substrate 1, mechanistic target of
      rapamycin and protein kinase B (also known as Akt). These changes have been
      reported to mediate insulin resistance. Taken together, an in vitro hepatic
      steatosis cell model was established in the present study, providing a valuable
      tool for understanding the pathogenesis of nonalcoholic fatty liver disease and
      associated insulin resistance, and for developing treatment strategies for this
      disease.

PMID- 29207075
TI  - Blocking interleukin-6 signaling inhibits cell viability/proliferation,
      glycolysis, and colony forming activity of human medulloblastoma cells.
AB  - Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have tumor
      promoting activity and are associated with poor survival outcomes in many
      cancers. Additionally, the IL-6/GP130/STAT3 axis has been widely studied due to
      its pivotal role in tumor development and maintenance in a number of tissue
      types, including the cerebellum. However, the connection between IL-6 signaling
      and medulloblastoma progression is largely unexplored. In the present study, we
      observed that IL-6 induced medulloblastoma cell viability, cell proliferation and
      glycolysis. Furthermore, it also upregulated the expression of phosphorylated
      STAT3, indicating that the IL-6/GP130/STAT3 pathway plays a central role in
      medulloblastoma. The FDA-approved drug bazedoxifene, a blocker of the formation
      of the hexameric IL-6/IL-6R/GP130 complex, was re-purposed in this study to
      inhibit the IL-6/GP130/STAT3 signaling pathway. Bazedoxifene not only inhibited
      IL-6 mediated cell viability and cell proliferation, and increased phosphorylated
      STAT3 expression, but it also decreased cell glycolysis, demonstrating a certain
      level of therapeutic efficacy in vitro. Collectively, our findings offer new
      insight into the molecular mechanism underlying the biological aggressiveness of
      medulloblastoma, the roles of IL-6 in these processes and a possible efficacious
      adjuvant therapy for medulloblastoma.

PMID- 29207077
TI  - Investigation of the pro-apoptotic effects of arbutin and its acetylated
      derivative on murine melanoma cells.
AB  - Arbutin, a natural polyphenol isolated from the bearberry plant Arctostaphylos
      uvaursi, possesses whitening and anticancer properties. The effects of arbutin on
      melanogenesis and its pro-apoptotic effect on B16 murine melanoma cells have not
      yet been reported. In the present study, acetylated arbutin was prepared in order
      to improve the biological effects of arbutin, and it was found to significantly
      inhibit the biosynthesis of melanin and tyrosinase activity compared with parent
      arbutin in B16 murine melanoma cells. Interestingly, only acetylated arbutin
      strongly inhibited B16 murine melanoma cell migration in a dose-dependent manner.
      Both arbutin and acetylated arbutin significantly reduced cell viability,
      promoted cell apoptosis, caused G1 cell cycle arrest and induced mitochondrial
      disruption in B16 murine melanoma cells. Furthermore, reduced expression of B
      cell lymphoma-extra large (Bcl-xL) and Bcl-2 were observed in arbutin- and
      acetylated arbutin-treated cells. Therefore, arbutin and acetylated arbutin were
      found to exert pro-apoptotic effects on B16 murine melanoma cells, mediated
      through the mitochondrial pathway. The findings of the present study also support
      the use of acetylated arbutin as a new potential candidate agent for skin
      whitening and melanoma treatment.

PMID- 29207076
TI  - Antiangiogenic effects of catalpol on rat corneal neovascularization.
AB  - To investigate the effects of catalpol on corneal neovascularization (CNV) and
      associated inflammation, eye drops (5 mM catalpol or PBS) were administered four
      times daily to alkali-burn rat models of CNV and inflammation. Clinical
      evaluations of CNV and the degree of inflammation were performed on days 0, 4, 7,
      10 and 14 under slit lamp microscopy. Eyes were collected on day 14 and prepared
      for hematoxylin and eosin, and immunofluorescence staining; corneal cell
      apoptosis was investigated via terminal deoxynucleotidyl transferase-mediated
      nick end labeling (TUNEL) staining. Protein expression levels of angiogenic and
      proinflammatory factors, including vascular endothelial growth factor (VEGF),
      pigment epithelium-derived factor (PEDF), tumor necrosis factor-alpha (TNF-alpha)
      and necrosis factor-kappaB (NF-kappaB) were determined by western blotting. The
      effects of catalpol on cell proliferation were investigated in vitro using human
      umbilical vein endothelial cells (HUVECs) and a Cell Counting kit-8 (CCK-8);
      alterations in migration and tube formation were investigated via HUVEC wound
      closure and tube formation assays. HUVEC viability and proliferative ability were
      inhibited in a dose-dependent manner; catalpol also decreased HUVEC cell
      migration and tube forming ability. Within alkali-burn rat models, decreased
      inflammation and CNV was associated with catalpol administration; as demonstrated
      with TUNEL, corneal cell apoptosis was decreased in response to catalpol. Western
      blot analysis revealed reduced protein expression levels of VEGF and TNF-alpha;
      however, PEDF and phosphorylated-NF-kappaB p65 were increased due to catalpol
      administration. The present study demonstrated the inhibitory effects exerted by
      catalpol on CNV and inflammation within alkali-burned rat models. Topical
      application of catalpol in vivo was associated with reduced CNV and inflammation;
      therefore, catalpol may be considered an anti-inflammatory agent for the clinical
      treatment of CNV.

PMID- 29207078
TI  - Characterizing key nucleotide polymorphisms of hepatitis C virus-disease
      associations via mass-spectrometric genotyping.
AB  - As more than 80% of hepatocellular carcinoma patients in Japan also suffer from
      hepatitis C virus infections some time in their medical history, identifying
      genetic aberrations associated to hepatitis C virulence in these individuals
      remains a high priority in the diagnosis and treatment of hepatocellular
      carcinoma. From the BioBank Japan Project, we acquired 480 subjects of
      hepatocellular carcinoma, chronic hepatitis and liver cirrhosis, and genotyped
      131 clinically relevant host single nucleotide polymorphisms to survey the
      potential association between certain risk alleles and genes to a patient's
      predisposition to hepatitis C and liver cancer. Among those polymorphisms, we
      found 12 candidates with statistical significance to support association with
      hepatitis C virus susceptibility and genetic predisposition to hepatocellular
      carcinoma. SNPs in genes such as XPC, FANCA, KDR and BRCA2 also suggested likely
      connections between hepatitis C virus susceptibility and the contraction of liver
      diseases. Single nucleotide polymorphisms reported here provided suggestions for
      genes as biomarkers and elucidated insights briefing the linkage of hepatitis C
      virulence to the alteration of healthy liver genomic landscape as well as liver
      disease progression.

PMID- 29207079
TI  - Molecular basis of coronary artery dilation and aneurysms in patients with
      Kawasaki disease based on differential protein expression.
AB  - Kawasaki disease (KD) is an acquired cardiac disease with a high incidence that
      affects children. KD has various complications, including coronary artery
      dilation (CAD) and coronary artery aneurysms (CAA). The identification of
      differentially expressed proteins and the underlying mechanisms may be the key to
      understanding differences between these KD complications. In the present study,
      isobaric tags for relative and absolute quantitation were used to identify
      variations in serum proteins between KD patients with CAD and CAA. In total, 87
      (37 upregulated and 50 downregulated) and 65 (33 upregulated and 32
      downregulated) significantly differentially-expressed proteins were identified in
      comparisons between control samples (healthy individuals) and those obtained from
      patients with KD and with CAD or CAA. Investigation into the underlying
      biological process revealed that variations between the two complications were
      associated with the wound healing response, as well as lipoprotein- and
      cholesterol-associated processes. Important proteins involved in the formation of
      the wound healing signaling network were identified via enriched biological
      processes and pathway analysis using ClueGo and ReactomeFIViz software. In the
      present study, 5 significantly differentially-expressed proteins, including
      mannose binding lectin 2 (MBL2), complement factor H (CFH), kininogen 1 (KNG1),
      serpin family C member 1 (SERPINC1) and fibronectin 1 (FN1), were selected and
      confirmed by western blotting. Analysis indicated that these proteins were
      associated to immunity, inflammation and metabolism, serving a key role within
      each module, which has never been reported previously. The present study proposed
      that MBL2, CFH, KNG1, SERPINC1 and FN1 may be a potentially excellent indicator
      group for distinguishing the two major KD complications, CAD and CAA.

PMID- 29207080
TI  - Effect of puerarin on collagen metabolism of fibroblasts in pelvic tissue of
      women with pelvic organ prolapse.
AB  - The aim of the present study was to investigate the protective effect of puerarin
      on pelvic organ prolapse (POP) and the underlying mechanisms that regulate the
      metabolism of human parametrial ligament fibroblasts (HPLFs). HPLFs obtained from
      the pelvic tissue of patients with (n=10) or without (n=8) POP during
      hysterectomy were isolated by enzymatic digestion and subsequently identified by
      immunocytochemistry in a previous study of the authors. Following this, cultured
      HPLFs were treated with 0.01, 0.10 or 1.00 mmol/l puerarin, followed by detection
      of proliferation rate by Cell Counting kit-8 assay. Following incubation with
      puerarin for 48 h, mRNA and protein expression levels of tissue inhibitor of
      metalloproteinase-1 (TIMP-1), matrix metalloproteinase (MMP)-2 and -9, and
      collagen (COL)I and III in HPLFs were quantified by reverse transcription
      quantitative polymerase chain reaction, and western blot and gelatin zymography
      analyses, respectively. MMP-2 and -9 expression levels were increased, whereas
      expression levels of TIMP-1, and COL I and III were decreased, in patients with
      POP compared with healthy controls. Following puerarin treatment, the expression
      levels of TIMP-1, and COL I and III were enhanced, whereas MMP-2 and -9 were
      inhibited. In conclusion, the present study demonstrated evidence increased
      degradation of the extracellular matrix in pelvic tissues of patients with POP
      compared with controls, and the protective effect of puerarin against POP via its
      anti-degradation effect on collagen. These results provide evidence for puerarin
      as a novel approach for the treatment of POP.

PMID- 29207081
TI  - Increased serum protein levels by Yuanshi Shengmai Chenggu Tablet in treatment of
      avascular osteonecrosis of the femoral head.
AB  - The traditional Chinese medicine (TCM) Yuanshi Shengmai Chenggu Tablet is used
      for treating the common orthopedic disease, hormone-induced avascular necrosis of
      the femoral head (ANFH) in China. However, its underlying mechanism and the
      changes induced in the treatment of ANFH remain to be fully elucidated. In the
      present study, through the use of isobaric Tag for Relative and Absolute
      Quantitation and multiple reaction monitoring quantifications, corticosteroid
      induced femoral head necrosis and the effects of treatment with Yuanshi Shengmai
      Chenggu Tablet were examined. The aim was to identify serum proteins, which may
      be potential serum markers for the early clinical diagnosis of ANFH, and maybe
      used to develop more rapid and convenient detection strategies. A total of five
      proteins were identified, comprising Ig mu chain C region, keratin, type I
      cytoskeletal 9, properdin, apolipoprotein A-IV, and IQ and AAA domain-containing
      protein 1. The expression levels of all five proteins were lower in ANFH and were
      higher following TCM treatment. These findings were confirmed using ELISA and
      western blot analysis.

PMID- 29207082
TI  - Autophagy regulates proliferation and biliary differentiation of hepatic oval
      cells via the MAPK/ERK signaling pathway.
AB  - Hepatic oval cells (HOCs) are thought to possess self-renewal ability and a
      bipotential capacity for differentiation, which allows them to differentiate into
      hepatocytes and cholangiocytes. Autophagy serves an important role in self
      renewal and differentiation of stem cells; however, how autophagy contributes to
      proliferation and differentiation of hepatic progenitor cells has yet to be
      elucidated. In the present study, autophagy was regulated by rapamycin (Rapa) and
      chloroquine (Chlo) administration. The results demonstrated that Chlo-treated
      HOCs exhibited decreased autophagic activity alongside a decreased tendency to
      proliferate, as determined by Cell Counting Kit-8. In addition, activation of
      autophagy by Rapa enhanced the biliary differentiation of HOCs. Furthermore,
      increased phosphorylated (p)-extracellular signal-regulated kinase (ERK)/p-p38
      expression was observed following the induction of autophagy, thus indicating
      that the mitogen-activated protein kinase (MAPK)/ERK signaling pathway was
      activated by autophagy to exert effects on the stimulation of HOC proliferation
      and differentiation. In conclusion, the present study demonstrated that autophagy
      regulates proliferation and biliary differentiation of HOCs via the MAPK/ERK
      signaling pathway. These results suggest a role for autophagy in stimulating the
      proliferation and differentiation of HOCs.

PMID- 29207083
TI  - A type 2 diabetes-associated SNP in KCNQ1 (rs163184) modulates the binding
      activity of the locus for Sp3 and Lsd1/Kdm1a, potentially affecting CDKN1C
      expression.
AB  - Although genome-wide association studies have shown that potassium voltage-gated
      channel subfamily Q member 1 (KCNQ1) is one of the genes that is most
      significantly associated with type 2 diabetes mellitus (T2DM), functionally
      annotating disease-associated single nucleotide polymorphisms (SNPs) remains a
      challenge. Recently, our group described a novel strategy to identify proteins
      that bind to SNP-containing loci in an allele-specific manner. The present study
      successfully applied this strategy to investigate rs163184, a T2DM susceptibility
      SNP located in the intronic region of KCNQ1. Comparative analysis of DNA-binding
      proteins revealed that the binding activities for the genomic region containing
      SNP rs163184 differed between alleles for several proteins, including Sp3 and
      Lsd1/Kdm1a. Sp3 preferentially bound to the non-risk rs163184 allele and
      stimulated transcriptional activity in an artificial promoter containing this
      region. Lsd1/Kdm1a was identified to be preferentially recruited to the non-risk
      allele of the rs163184 region and reduced Sp3-dependent transcriptional activity
      in the artificial promoter. In addition, expression of the nearby cyclin
      dependent kinase inhibitor 1C (CDKN1C) gene was revealed to be upregulated after
      SP3 knockdown in cells that possessed non-risk alleles. This suggests that CDKN1C
      is potentially one of the functional targets of SNP rs163184, which modulates the
      binding activity of the locus for Sp3 and Lsd1/Kdm1a.

PMID- 29207084
TI  - Promoter hypermethylation may contribute to E-cadherin repression in the human
      salivary carcinoma ex pleomorphic adenoma.
AB  - The role of promoter methylation in the inactivation of E-cadherin (CDH1) in
      salivary carcinoma ex pleomorphic adenoma (CXPA) is unknown. The objective of
      this study was to determine the role and potential clinical implications of CDH1
      promoter methylation in salivary CXPA. The CDH1 promoter methylation status was
      determined by bisulfite sequencing PCR in 37 primary CXPA tissues and 2 CXPA cell
      lines. E-cadherin expression levels were determined by immunohistochemical
      analysis of each tumor. E-cadherin protein levels and CDH1 mRNA levels were
      examined by immunoblotting and quantitative real-time PCR, respectively, in 2
      CXPA cell lines. Cells were treated with 5-Aza-dC or TGF-beta1 to test the
      influence of promoter methylation on CDH1 mRNA and protein expression.
      Associations between CDH1 molecular alterations and patients' clinicopathologic
      characteristics and prognosis were statistically evaluated. CDH1 promoter
      hypermethylation was detected in 21 of 37 tumors (56.76%). Of these 37 tumors, 13
      tumors (35.14%) showed low E-cadherin expression. Tumors that had CDH1 promoter
      methylation had a histological tendency toward luminal differentiation (P=0.004),
      high tumor grade (P=0.005), high T stage (P=0.024) and high TNM stage (P=0.038)
      compared with tumors that did not. The two CXPA cell lines exhibited an inverse
      relationship between CDH1 promoter methylation status and CDH1 mRNA and protein
      expression. Treatment of the hypermethylated cell line with 5-Aza-dC restored
      CDH1 mRNA and E-cadherin protein expression. The induction of hypermethylation by
      TGF-beta1 resulted in the repression of CDH1 mRNA and protein expression. CDH1 is
      commonly silenced in CXPA through promoter methylation. CDH1 methylation is
      closely related to tumor cell differentiation, histological grade, lymph node
      metastasis and advanced TNM stage, indicating that CDH1 methylation may play a
      role in the initiation and progression of CXPA.

PMID- 29207085
TI  - Chronic prenatal hypoxia impairs cochlear development, a mechanism involving
      connexin26 expression and promoter methylation.
AB  - Chronic prenatal hypoxia is a damaging to fetal development and may have various
      consequences, including hearing loss. Connexin 26 (Cx26) is one of the major
      protein subunits required for gap junction formation, and has an important role
      in maintaining homeostasis in the cochlea and normal hearing. Cx26 mutation and
      expression abnormality are closely associated with inherited nonsyndromic
      deafness, but the association between Cx26 and prenatal hypoxia is less
      established. The present study aimed to examine Cx26 expression and aberrant
      methylation the Cx26 promoter region in the cochlea from rats exposed to chronic
      prenatal hypoxia. Hematoxylin and eosin staining demonstrated that the number of
      hair cells in the organ of Corti were less in the hypoxia group. Reverse
      transcription-quantitative polymerase chain reaction and western blot analysis
      revealed that protein and mRNA levels of Cx26 were decreased in the hypoxia group
      compared with the control group. Further bisulfite sequencing analysis revealed
      that prenatal hypoxia significantly increased the methylation status of the
      promoter region of the Cx26 gene. These results demonstrate that chronic prenatal
      hypoxia caused hearing impairment, and suggest that promoter region
      hypermethylation and expression downregulation of Cx26 underlie the mechanism of
      action.

PMID- 29207086
TI  - Tan IIA inhibits H1299 cell viability through the MDM4-IAP3 signaling pathway.
AB  - Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots
      of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell
      proliferation and induce apoptosis. However, the mechanisms underlying the
      function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of
      the present study was to identify the molecular mechanisms underlying the anti
      cancer effects of Tan IIA in p53-deficient H1299 cells. Tan IIA was demonstrated
      to suppress murine double minute 4 (MDM4) expression in a time- and dose
      dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA-induced
      downregulation of MDM4 resulted in an increase of P73alpha and a decrease of
      inhibitor of apoptosis 3 (IAP3). However, P73alpha was not activated as two
      P73alpha target genes, BCL2 binding component 3 and phorbol-12-myristate-13
      acetate-induced protein 1, were not significantly induced. Tan IIA-induced
      inhibition of IAP3 expression may be involved in Tan IIA-induced apoptosis and
      inhibition of H1299 cell viability. Notably, a combination of Tan IIA and
      doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299
      cells, indicating that Tan IIA sensitized p53-deficient and MDM4-overexpressing
      H1299 cells to DOX-induced apoptosis.

PMID- 29207087
TI  - p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and
      results from the BIG 2-98 phase III trial.
AB  - In the present study, in order to investigate the role of signal transducer and
      activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast
      cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and
      investigated its effect on the outcome in a pooled analysis and in a large
      prospective adjuvant trial. By using the TCGA repository, we developed gene
      signatures that reflected the level of p-STAT3. Using pooled analysis of the
      expression data from luminal breast cancer patients, we assessed the effects of
      the p-STAT3 expression signature on prognosis. We further validated the p-STAT3
      prognostic effect using immunohistochemistry (IHC) and immunofluorescence
      staining of p-STAT3 tissue microarrays from a large randomised prospective trial.
      Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type
      breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated
      with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression
      signature identified patients with a good prognosis irrespective of the luminal
      subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by
      IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples
      (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1
      years, p-STAT3 was associated with a reduced risk of recurrence in ER
      positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98;
      P=0.04). On the whole, our data indicate that p-STAT3 is associated with an
      improved outcome in ER-positive breast cancer.

PMID- 29207088
TI  - Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal
      carcinoma.
AB  - Luteolin is a falconoid compound that is present in various types of plants and
      possesses remarkable potential as a chemopreventive agent. However, the poor
      aqueous solubility of luteolin limits its clinical application. In the present
      study, an approach towards chemoprevention was explored using liposomes to
      deliver luteolin, and the antitumor efficacy was investigated in colorectal
      carcinoma. The present findings demonstrated that luteolin was efficiently
      encapsulated into liposomes with an encapsulation efficiency as high as 90%. The
      particle size of the liposomal luteolin (Lipo-Lut) and zeta-potential were
      optimized. In vitro studies demonstrated that, Lipo-Lut had a significant
      inhibitory effect on the growth on the CT26 colorectal carcinoma cell line
      compared with free luteolin (Free-Lut). The in vivo study indicated that Lipo-Lut
      could achieve superior antitumor effects against CT26 tumor compared with
      luteolin alone. The present results suggested that liposome delivery of luteolin
      improved solubility, bioavailability and may have potential applications in
      chemoprevention in clinical settings.

PMID- 29207089
TI  - Overexpression of p16ink4a regulates the Wnt/beta-catenin signaling pathway in
      pancreatic cancer cells.
AB  - The pathogenesis and etiology of pancreatic cancer remain to be fully elucidated;
      therefore, associated investigations are required to improve the outcome and
      prognosis of patients. In the present study, the effects of the overexpression of
      p16ink4a on the Wnt/beta-catenin signaling pathway were investigated in
      pancreatic cancer cell lines. Two pancreatic cancer cell lines, Bxpc-3 and
      Miapaca-2, characterized by low expression of p16ink4a, were transfected with the
      pc-DNA3.0-p16ink4a plasmid. After 24 h, Reverse transcription-polymerase chain
      reaction and western blot analyses were performed to evaluate the expression of
      p16ink4a, beta-catenin, which is a key molecule in the Wnt/beta-catenin signaling
      pathway, c-myc and cyclin D1, which are molecules downstream of beta-catenin. The
      expression of p16ink4a was significantly upregulated in the transfected cells.
      Consequently, the expression of beta-catenin was inhibited, whereas the
      expression levels of c-myc and cyclin D1 were not altered significantly. The
      increased expression of p16ink4a may affect the activity of Wnt/beta-catenin
      signaling through modulation of the expression of beta-catenin. The results of
      the present study provide information for the future development of targeted
      treatments for pancreatic cancer.

PMID- 29207090
TI  - Long intergenic non-coding RNA-p21 mediates cardiac senescence via the Wnt/beta
      catenin signaling pathway in doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (Dox)-induced cardiotoxicity has been a well-known phenomenon to
      clinicians and scientists for decades. It has been confirmed that Dox-dependent
      cardiotoxicity is accompanied by cardiac cellular senescence. However, the
      molecular mechanisms underlying Dox cardiotoxicity remains to be fully
      elucidated. Long non-coding (lnc) RNAs regulate gene transcription and the fate
      of post-transcriptional mRNA, which affects a broad range of age-associated
      physiological and pathological conditions, including cardiovascular disease and
      cellular senescence. However, the functional role of lncRNAs in Dox-induced
      cardiac cellular senescence remains largely unknown. Using the reverse
      transcription-quantitative polymerase chain reaction method, the present study
      indicated that long intergenic non-coding (linc) RNA-p21 was highly expressed in
      Dox-treated HL-1 murine cardiomyocytes. Dox-induced cardiac senescence was
      accompanied by decreased cellular proliferation and viability, increased
      expression of p53 and p16, and decreased telomere length and telomerase activity,
      while these effects were relieved by silencing endogenous lincRNA-p21. We found
      that lincRNA-p21 interacted with beta-catenin and that silencing beta-catenin
      abolished the anti-senescent effect of lincRNA-p21 silencing. It was observed
      that modulating lincRNA-p21 to exert an anti-senescent effect was dependent on
      decreasing oxidant stress. To conclude, the present findings suggest that lincRNA
      p21 may be involved in Dox-associated cardiac cellular senescence and that
      silencing lincRNA-p21 effectively protects against Dox cardiotoxicity by
      regulating the Wnt/beta-catenin signaling pathway and decreasing oxidant stress.
      Furthermore, modulating lincRNA-p21 may have cardioprotective potential in
      patients with cancer receiving Dox treatment.

PMID- 29207091
TI  - Fibroblast activation protein-alpha in tumor cells promotes colorectal cancer
      angiogenesis via the Akt and ERK signaling pathways.
AB  - Fibroblast activation protein-alpha (FAP-alpha) is a cell surface serine protease
      of the post-prolyl peptidase family, and stromal FAP-alpha expression may serve
      important functions in tumor occurrence and progression. In recent years, FAP
      alpha expression in tumor cells has been detected in a number of types of tumor,
      and its roles in tumor growth and metastasis have been reported. However, the
      presence of FAP-alpha in colorectal cancer (CRC) cells lacks sufficient evidence
      and its role in angiogenesis remains unknown. The present study confirmed FAP
      alpha expression in CRC cells at the tissue and cellular level, using
      immunohistochemistry and western blot analysis, respectively; it additionally
      identified that FAP-alpha in CRC cells was positively associated with vascular
      endothelial growth factor (VEGF)-A expression and microvessel density in stained
      tissue samples for the first time. In addition, western blotting identified that
      FAP-alpha overexpression in SW1116 cells significantly upregulated VEGF-A
      expression, and silencing of FAP-alpha in HT29 cells markedly inhibited VEGF-A
      expression. Survival analysis demonstrated that patients with high expression of
      FAP-alpha and VEGF-A had the shortest survival time. To detect the effects of FAP
      alpha on human umbilical vein endothelial cells (HUVECs), conditioned medium (CM)
      from CRC cell lines was used and it was identified that CM from SW1116 cells with
      overexpressed FAP-alpha exhibited significantly increased VEGF-R2, phosphorylated
      extracellular signal-regulated kinase (p-ERK) and p-RAC-alpha serine/threonine
      protein kinase (Akt) in HUVECs, in addition to the proliferation rate.
      Conversely, CM from HT29 cells with FAP-alpha silenced exhibited a significantly
      inhibited proliferation rate. Molecular mechanism analysis demonstrated that p
      ERK and p-Akt in SW1116 and HT29 cells were affected by alterations in FAP-alpha
      expression, and treatment with a p-ERK inhibitor (U0126) and p-Akt inhibitor
      (LY294002) ameliorated VEGF-A upregulation induced by FAP-alpha overexpression.
      All the results confirmed the presence of FAP-alpha in CRC cells and suggested
      that FAP-alpha may effectively promote angiogenesis in CRC via the Akt and ERK
      signaling pathways.

PMID- 29207092
TI  - Lycium barbarum polysaccharide arbitrates palmitate-induced apoptosis in MC3T3-E1
      cells through decreasing the activation of ERS-mediated apoptosis pathway.
AB  - Palmitate (PA) has been identified to induce cell apoptosis in osteoblasts. The c
      Jun NH2-teminal kinase (JNK) signaling pathway and endoplasmic reticulum stress
      (ERS) were found to be important contributors. Therefore, natural or synthetic
      agents may antagonize PA-induced apoptosis in osteoblasts, and demonstrate the
      potential application to reverse osteoporosis. The present study demonstrated
      that the Lycium barbarum polysaccharide (LBP) is as a major active ingredient of
      Lycium barbarum and that it can reduce the fatty acid toxicity of PA.
      Furthermore, this study attempted to elucidate the underlying molecular
      mechanisms of LBP. Firstly, it was demonstrated via a Cell Counting Kit-8 assay,
      that LBP could significantly increase the viability of MC3T3-E1 cells in a dose
      dependent manner. Flow cytometric analysis indicated that LBP inhibits PA-induced
      apoptosis in osteoblastic cells. Reverse transcription-quantitative polymerase
      chain reaction and western blotting results showed that the expression levels of
      glucose-regulated protein 78, C/EBP homologous protein and cysteinyl asparate
      specific proteinase-3/-9/-12, were increased in MC3T3-E1 cells following PA
      treatment. The treatment of the cells with PA resulted in an activation of the
      ERS and the JNK signaling pathway. These pathways were effectively suppressed by
      co-incubation with LBP. Taken together, PA may cause ERS, in cell apoptosis, and
      it may further activate the JNK signaling pathway. LBP reversed PA-induced
      apoptosis in MC3T3-E1 cells through inhibition of the activation of the ERS
      mediated JNK signaling pathway.

PMID- 29207093
TI  - Potential inhibitory effects of the traditional herbal prescription Hyangso-san
      against skin inflammation via inhibition of chemokine production and inactivation
      of STAT1 in HaCaT keratinocytes.
AB  - Inflammatory skin disease are caused by multiple factors, including
      susceptibility genes, and immunologic and environmental factors, and are
      characterized by an increase in epidermal thickness and the infiltration of
      macrophages, keratinocytes, mast cells, eosinophils and other inflammatory cells.
      Keratinocytes may serve an important role in the pathogenesis of inflammatory
      skin diseases. The traditional herbal decoction Hyangso-san (HSS) has been used
      to treat symptoms of the common cold, including headache, pantalgia, fever and
      chills. However, to the best of our knowledge, there is no evidence regarding
      whether HSS has an effect on inflammatory skin diseases. The present study
      investigated the anti-skin inflammation activity of HSS using the HaCaT human
      keratinocyte cell line. The mRNA expression and production of inflammatory
      chemokines, including C-C motif chemokine ligand 22 (CCL22), CCL5, CCL17, and
      interleukin (IL)-8, was measured using reverse transcription polymerase chain
      reaction and ELISA analyses. Moreover, we evaluated the effect of HSS on signal
      transducer and activator of transcription 1 (STAT1) pathway in HaCaT cells. The
      cells were stimulated with tumor necrosis factor-alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) to induce an inflammatory reaction. In the TNF-alpha- and IFN
      gamma-stimulated cells, the production and expression of inflammatory chemokines
      were observed, including CCL22, CCL5, CCL17 and IL-8. In addition, stimulation
      with TNF-alpha and IFN-gamma increased the phosphorylation and nuclear
      translocation of STAT1 in HaCaT cells. By contrast, HSS extract treatment
      inhibited TNF-alpha- and IFN-gamma-induced STAT1 activation. Results from the
      present study indicated that HSS exhibited inhibitory effects on TNF-alpha- and
      IFN-gamma-mediated chemokine production and expression by targeting STAT1 in
      keratinocytes. Overall, the results indicated that HSS may be a potential
      candidate therapeutic drug for inflammatory skin diseases such as atopic
      dermatitis.

PMID- 29207094
TI  - MicroRNA-132 modifies angiogenesis in patients with ischemic cerebrovascular
      disease by suppressing the NF-kappaB and VEGF pathway.
AB  - In the present study, the expression of microRNA (miR)-132 and the mechanism by
      which it modifies angiogenesis in patients with ischemic cerebrovascular disease
      (ICD) was investigated. RNA isolation and reverse transcription-quantitative
      polymerase chain reaction were used to measure miR-132 expression in patients
      with ICD. Inflammatory factors were measured using ELISA kits and western
      blotting measured B-cell lymphoma-2 (Bcl-2)-associated X/Bcl-2 ratio (Bax/Bcl-2
      ratio), nuclear factor (NF)-kappaB p65, matrix metalloproteinase-9 (MMP-9),
      vascular cell adhesion molecule-1 (VCAM-1) and protein expression of inducible
      nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF)
      protein expression. miR-132 expression in patients with ICD was lower compared
      with healthy volunteers. PC12 cells were used to create an oxygen glucose
      deprivation (OGD) model. miR-132 overexpression in an in vitro model was able to
      reduce tumor necrosis factor-a, interleukin (IL)-1beta, IL-6, IL-8,
      cyclooxygenase-2, caspase-3 and caspase-9 levels, suppress Bax/Bcl-2 ratio, NF
      kappaB p65, MMP-9, VCAM-1, iNOS, VEGF protein expression. The results suggested
      that miR-132 may modify angiogenesis in patients with ICD by suppressing the NF
      kappaB pathway and promoting the VEGF pathway, and may develop into a therapy for
      ICD in future research.

PMID- 29207095
TI  - Upregulation of ZBTB7A exhibits a tumor suppressive role in gastric cancer cells.
AB  - Gastric cancer presents as a complex solid tumor and is the third leading cause
      of global cancer-associated mortality. The genetic alterations in gastric cancer
      remain unclear and deserve further investigation. Mining The Cancer Genome Atlas
      gastric adenocarcinoma dataset identified a frequent loss of the zinc finger and
      BTB domain containing 7A (ZBTB7A) gene locus and a significant correlation
      between low ZBTB7A expression and poor patient survival. ZBTB7A belongs to the
      POZ/BTB and Kruppel transcription factor family. In the present study,
      overexpression of ZBTB7A in a gastric cancer cell line induced cell cycle arrest
      at the S phase. Upregulation of ZBTB7A also promoted apoptosis and repressed cell
      migration. The results of the present study indicated that ZBTB7A functions as a
      tumor suppressor in gastric cancer cells. Understanding the role of ZBTB7A in
      gastric cancer may provide important clinical insight for treatment.

PMID- 29207096
TI  - Therapeutic effect of herb residue fermentation supernatant on spleen-deficient
      mice.
AB  - To minimize the waste of active ingredients present in herb residues, in the
      present study, probiotics of Bacillus subtilis, Aspergillus oryzae and
      Lactobacillus plantarum M3 were selected to reuse herb residues from
      Jianweixiaoshi tablets, and the therapeutic effects of the herb residue
      fermentation supernatant were evaluated using a spleen-deficient mouse model. The
      results of the present study indicated that the fermentation supernatant may
      effectively improve the immunity of mice, as measured by body weight, spleen and
      thymus index, and inflammatory cytokines, including interleukin (IL)-2, IL-4 and
      interferon-gamma. The viable cell count and denaturing gradient gel
      electrophoresis results indicated that the fermentation supernatant markedly
      enhanced bacterial diversity and the number of lactobacilli in mouse intestines.
      Therefore, the combination of the Jianweixiaoshi herb residue and probiotics
      provided a novel method to reuse herb residues and may in the future contribute
      to the treatment of spleen deficiency.

PMID- 29207097
TI  - The anticancer effects of Cucurbitacin I inhibited cell growth of human non-small
      cell lung cancer through PI3K/AKT/p70S6K pathway.
AB  - The present study aimed to identify potential anticancer effects of Cucurbitacin
      I regulators on cell growth of human non-small cell lung cancer (NSCLC) and to
      explore their mechanism. The results indicated that the anticancer effects of
      Cucurbitacin I markedly attenuated cell proliferation, and induced apoptosis in
      NSCLC. Furthermore, Cucurbitacin I suppressed phosphatidylinositol-4,5
      bisphosphate 3-kinase (PI3K), phosphorylation (p)-AKT and p-p70S6K pathway in
      NSCLC. Then, (PI3K) inhibitor increased anticancer effects of Cucurbitacin I on
      NSCLC. In conclusion, the present results indicated that Cucurbitacin I inhibited
      cell growth of human NSCLC through PI3K/AKT/p70S6K signaling pathway.

PMID- 29207098
TI  - FOXO1 is crucial in glioblastoma cell tumorigenesis and regulates the expression
      of SIRT1 to suppress senescence in the brain.
AB  - In the present study, the role of Forkhead Box O1 (FOXO1) in glioblastoma (GBM)
      cell tumorigenesis was examined and the underlying mechanisms were investigated.
      Reverse transcription-quantitative polymerase chain reaction and western blot
      analyses were used to analyze the expression of FOXO1 in GBM cell lines (LN18 and
      T98G) and tissues. Compared with the control groups, FOXO1 was significantly
      downregulated in the GBM tissues and GBM cell lines (P<0.05). The effects of the
      expression of FOXO1 on GBM cell proliferation and cell cycle were examined using
      flow cytometry. The overexpression of FOXO1 markedly inhibited LN18 and T98G cell
      proliferation and arrested cell cycle at the G0/G1 phase. In addition, FOXO1
      facilitated cell senescence through regulation of the expression of sirtuin 1.
      Epithelial-mesenchymal transition (EMT) is a complex process, which affects cell
      growth, invasion and metastasis. The results of the present study revealed that
      FOXO1 inhibited EMT and metastasis in GBM. These finding revealed a novel
      mechanism of FOXO1 in the suppression of tumorigenesis and metastasis of GBM
      cells and suggested that FOXO1 may be a potential therapeutic target for treating
      GBM.

PMID- 29207099
TI  - N-acetylcysteine ameliorates contrast-induced kidney injury in rats with
      unilateral hydronephrosis.
AB  - The aim of the present study was to investigate the protective effects of N
      acetylcysteine (NAC) on contrast-induced acute kidney injury in rats with
      unilateral hyronephrosis. Eighty-two male Sprague Dawley rats were randomized to
      undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68).
      After 3 weeks, the UUO animals were randomized to three groups: NAC gastric
      perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24);
      and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were
      injected with iohexol. One day after contrast, half of the rats were sacrificed
      to assess the pathological changes to the kidneys, serum creatinine, serum
      neutrophil gelatinase-associated lipocalin (NGAL), renal cell apoptosis rate and
      expression of apoptosis regulators Bcl-2/Bax. The remaining rats underwent
      obstruction relief and were analyzed 3 weeks later. Compared with the controls,
      serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3
      weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum
      NGAL levels compared with UUO+iohexol rats (all P<0.05). Following modeling,
      UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular
      cells, higher expression of Bax mRNA, and lower ratio of Bcl-2/Bax (all P<0.05).
      Three weeks after obstruction relief, UUO+iohexol+NAC rats exhibited a lower
      apoptosis rate, lower Bax mRNA expression, higher expression of Bcl-2 mRNA and
      higher ratio of Bcl-2/Bax (all P<0.05) compared with day 1 following drug
      administration. The prophylactic use of NAC reduced the apoptotic rate of renal
      tubular cells following contrast exposition, which was accompanied by changes in
      the expression of Bcl-2/Bax mRNA.

PMID- 29207100
TI  - Retinal microvasculature alteration in central serous chorioretinopathy.
AB  - The aim of the present study was to investigate the changes of retinal
      microvascular network in patients with central serous chorioretinopathy (CSCR). A
      total of fifteen patients (right eye) with CSCR and 15 normal controls (right
      eye) were recruited. We used optical coherence tomography angiography to scan 6x6
      mm macular retinal blood flow images with the application of a series of
      customized image segmentation processing program software to obtain microvascular
      and macrovascular density, and compared the superficial microvascular (SMIR),
      superficial macrovascular ring (SMAR) and the superficial total microvascular
      (STMI) density between CSCR patients and control group. Using the annular
      partition (C1-C6) and quadrant partition methods on the macular, we compared the
      retinal vessel density changes. We also performed ROC analysis of superficial
      retinal microvessel density in CSCR retina to investigate the relationship
      between the microvascular density, the foveal thickness and visual acuity. The
      density of STMI and SMIR decreased in macular area in the patients with CSCR
      compared to the normal controls (P<0.05), while the density of SMAR did not
      change significantly. We found no significant difference in the density of SMIR
      with the quadrant partition method, whereas the annular partition method showed
      significantly decreased SMIR density only in the C1 region in patients with CSCR
      (P<0.05), with no significant difference observed in C2-C6 regions. The density
      of SMIR had the highest differentiation power in the CSCR group, whereas the
      density of SC1 ring had the lowest differentiation power by the annular method.
      The largest area under the ROC curves was 0.77. The correlation index of the SMIR
      density and visual acuity was -0.544, whereas macular thickness and visual acuity
      was -0.644 in the CSCR group. The density of STMI and SMIR were decreased in
      patients with CSCR, which might provide further understanding of the pathogenesis
      of CSCR.

PMID- 29207101
TI  - Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease
      through the AMPK and LXR signaling pathways.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a major public health concern
      worldwide. The aim of the present study was to observe the effect of diosgenin on
      NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased
      the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA
      carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose
      (HG)-induced triglyceride (TG) accumulation and sterol regulatory element-binding
      protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially
      abolished by the AMPK inhibitor compound C. Diosgenin also significantly
      inhibited the increase of liver X receptor (LXR) alpha mRNA induced by HG or
      T0901317. However, T0901317-induced upregulation of LXRalpha and SREBP-1c mRNA
      was not blocked by compound C. Following a high-fat diet for 16 weeks, the body
      and liver weights of the experimental rats were significantly increased, but this
      effect was significantly suppressed by diosgenin. Diosgenin and fenofibrate
      ameliorated lipid deposition in the liver and reduced the increase of hepatic TG
      content. Diosgenin significantly decreased the alanine aminotransferase (ALT)
      level, whereas fenofibrate significantly increased the ALT and aspartate
      aminotransferase levels. Diosgenin also increased AMPK and ACC phosphorylation
      and suppressed LXRalpha in the liver. In conclusion, the results of the present
      study suggested that diosgenin is a potential agent for preventing the
      development of NAFLD through the AMPK and LXR signaling pathways.

PMID- 29207102
TI  - LncRNA TUG1 serves an important role in hypoxia-induced myocardial cell injury by
      regulating the miR-145-5p-Binp3 axis.
AB  - The aim of the present study was to investigate the function of long non-coding
      RNA TUG1 in hypoxia-induced myocardial cell injury and to explore the potential
      molecular mechanisms. The cardiomyocyte cell line H9c2 was cultured under hypoxic
      and normoxic conditions. TUG1 expression under hypoxic conditions was then
      detected. The effects of TUG1 overexpression on viability, apoptosis, migration
      and invasion were assayed. In addition, the microRNA (miR)-145-5p expression was
      detected. Following H9c2 cell transfection with miR-145-5p mimics, the H9c2 cell
      viability, apoptosis, migration and invasion were also detected. Additionally,
      the target gene of miR-145-5p was assayed by Luciferase reporter assay. The
      protein expressions of Wnt-3a, Wnt5a, and beta-catenin in H9c2 cells under
      hypoxic conditions were also determined. The results revealed that hypoxia
      induced injury in H9c2 cells, including inhibiting cell viability, migration and
      invasion, and promoting cell apoptosis. Overexpression of TUG1 aggravated hypoxia
      induced injury in H9c2 cells. In addition, miR-145-5p was negatively regulated by
      TUG1, and TUG1 overexpression aggravated hypoxia-induced injury via the
      downregulation of miR-145-5p. Furthermore, B-cell lymphoma 2 interacting protein
      3 (Bnip3) was a target of miR-145-5p, and overexpression of Bnip3 aggravated
      hypoxia-induced cell injury by activating Wnt/beta-catenin signaling pathways in
      H9c2 cells. In conclusion, overexpression of TUG1 aggravated hypoxia-induced
      injury in cardiomyocytes by regulating the miR-145-5p-Binp3 axis. Activation of
      the Wnt/beta-catenin signaling pathway may be a key mechanism to mediate the role
      of TUG1 in regulating hypoxia-induced myocardial injury. TUG1 may be an effective
      diagnostic marker and therapeutic target for myocardial ischemia.

PMID- 29207103
TI  - Epigenetic alterations of the Igf2 promoter and the effect of miR-483-5p on its
      target gene expression in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most widespread
      malignancies in China. MicroRNAs (miRNAs/miRs) are endogenous evolutionarily
      conserved small non-coding RNAs that are able to regulate ESCC formation and
      deterioration by negatively regulating specific target genes. In the present
      study, the expression levels of miR-483-5p and its associated mRNAs were measured
      by quantitative polymerase chain reaction (PCR) analysis, and the methylation
      levels of the insulin-like growth factor 2 (Igf2) promoter were detected via the
      methylation-specific PCR method in serum and tissues from patients with ESCC. The
      results demonstrated that the expression level of miR-483-5p was significantly
      upregulated in preoperative serum and cancer tissues from patients with ESCC
      (P<0.01), and the miR-483-5p expression levels were correlated with the tumor,
      node, metastasis stage (P<0.05) and lymph node metastasis (P<0.05). In addition,
      the mRNA levels of miR-483-5p target genes (Rho GDP dissociation inhibitor alpha,
      activated leukocyte cell adhesion molecule, and suppressor of cytokine signaling
      3) in cancer tissues were significantly decreased compared with adjacent non
      cancerous tissues. These results indicated that miR-483-5p and its target genes
      may be involved in the developmental process of ESCC. The Igf2 levels in cancer
      tissues were significantly increased compared with adjacent non-cancerous tissues
      (P<0.01). Additionally, the methylation levels of the Igf2 promoter region were
      31.82 and 54.55% in cancer tissues and adjacent non-cancerous tissues,
      respectively, suggesting that low methylation of the Igf2 gene promoter region
      may promote the expression of Igf2 and miR-483-5p; this, in turn, induces the
      degradation of miR-483-5p target genes, and leads to the upregulation of
      oncogenes and the downregulation of tumor suppressors, which promotes the
      development of ESCC.

PMID- 29207105
TI  - microRNA-363-3p inhibits cell growth and invasion of non-small cell lung cancer
      by targeting HMGA2.
AB  - Lung cancer is the second most common cancer and is the leading cause of cancer
      related death worldwide. For decades, increasing evidence revealed that microRNAs
      may contribute to non-small cell lung cancer (NSCLC) carcinogenesis and
      progression and could provide novel therapeutic targets for treatments of
      patients with NSCLC. Accumulated studies indicate that microRNA (miR)-363-3p
      serves important roles in tumorigenesis and tumor development; however, the role
      of miR-363-3p in NSCLC is still unclear. The current study reported that miR-363
      3p exhibited reduced expression in NSCLC tissues and cell lines. Reduced miR-363
      3p expression was correlated with tumor node metastasis classification and
      distant metastasis of NSCLC patients. Notably, miR-363-3p re-expression
      significantly suppressed cell proliferation and invasion of NSCLC. Furthermore,
      bioinformatics analysis, luciferase reporter assay, reverse transcription
      quantitative polymerase chain reaction and western blotting indicated that (high
      mobility group AT-hook 2) HMGA2 was a direct target gene of miR-363-3p. HMGA2 was
      increased in NSCLC tissues and inversely associated with HMGA2 expression.
      Moreover, HMGA2 underexpression had similar effects to miR-363-3p overexpression
      in NSCLC cells. Thus, the current study suggested that miR-363-3p may act as a
      tumor suppressor in NSCLC and that the miR-363-3p could be investigated as a
      therapeutic target for the patients with this disease.

PMID- 29207104
TI  - The role and mechanism of beta-arrestins in cancer invasion and metastasis
      (Review).
AB  - beta-arrestins are a family of adaptor proteins that regulate the signaling and
      trafficking of various G protein-coupled receptors (GPCRs). They consist of beta
      arrestin1 and beta-arrestin2 and are considered to be scaffolding proteins. beta
      arrestins regulate cell proliferation, promote cell invasion and migration,
      transmit anti-apoptotic survival signals and affect other characteristics of
      tumors, including tumor growth rate, angiogenesis, drug resistance, invasion and
      metastatic potential. It has been demonstrated that beta-arrestins serve roles in
      various physiological and pathological processes and exhibit a similar function
      to GPCRs. beta-arrestins serve primary roles in cancer invasion and metastasis
      via various signaling pathways. The present review assessed the function and
      mechanism of beta-arrestins in cancer invasion and metastasis via multiple
      signaling pathways, including mitogen-activated protein kinase/extracellular
      signal regulated kinase, Wnt/beta-catenin, nuclear factor-kappaB and
      phosphoinositide-3 kinase/Akt.

PMID- 29207106
TI  - LncRNA SNHG12 regulates gastric cancer progression by acting as a molecular
      sponge of miR-320.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. Previous
      studies have focused on long non-coding RNAs (lncRNAs), which have important
      roles in the development and progression of GC. The present study aimed to
      clarify the expression and function of lncRNA small nucleolar RNA host gene 12
      (SNHG12) in GC. The expression and the clinical characteristics of GC were
      analyzed in the samples from patients with GC and matched adjacent normal
      tissues. The present study determined that SNHG12 was significantly overexpressed
      in GC and its expression level was highly associated with tumor size, tumor-node
      metastasis stage, distant metastasis, lymphatic metastasis. Patients with high
      SNHG12 expression had a short survival period. Additionally, inhibition of SNHG12
      in GC cell lines SGC-7901 and AGS suppressed cell growth, colony formation,
      proliferation and invasion. MicroRNA (miR)-320, a putative target gene of SNHG12,
      was inversely correlated with SNHG12 expression in GC tissues and cell lines. In
      addition, the present study determined that miR-320 was directly regulated by
      SNHG12 and suppression of miR-320 expression reversed the inhibitory effects of
      SNHG12 siRNA on GC cell proliferation and invasion. These findings revealed that
      SNHG12 acts as a tumor promoter by directly targeting miR-320 in GC, suggesting a
      potential novel biomarker for the diagnosis and prognosis of GC.

PMID- 29207107
TI  - Modular organization of a hypocretin gene minimal promoter.
AB  - Orexins or hypocretins are neurotransmitters produced by a small population of
      neurons in the lateral hypothalamus. This family of peptides modulates sleep-wake
      cycle, arousal and feeding behaviors; however, the mechanisms regulating their
      expression remain to be fully elucidated. There is an interest in defining the
      key molecular elements in orexin regulation, as these may serve to identify
      targets for generating novel therapies for sleep disorders, obesity and
      addiction. Our previous studies showed that the expression of orexin was
      decreased in mice carrying null-mutations of the transcription factor early B
      cell factor 2 (ebf2) and that the promoter region of the prepro-orexin (Hcrt)
      gene contained two putative ebf-binding sites, termed olf-1 sites. In the present
      study, a minimal promoter region of the murine Hcrt gene was identified, which
      was able to drive the expression of a luciferase reporter gene in the human 293
      cell line. Deletion of the olf1-site proximal to the transcription start site of
      the Hcrt gene increased reporter gene expression, whereas deletion of the distal
      olf1-like site decreased its expression. The lentiviral transduction of murine
      transcription factor ebf2 cDNA into 293 cells increased the gene expression
      driven by this minimal Hcrt-gene promoter and an electrophoretic mobility shift
      assays demonstrated that the distal olf1-like sequence was a binding site for
      ebf2.

PMID- 29207108
TI  - Integrated analysis of gene expression and copy number variations in MET proto
      oncogene-transformed human primary osteoblasts.
AB  - The aim of the present study was to screen the potential osteosarcoma (OS)
      associated genes and to obtain additional insight into the pathogenesis of OS.
      Transcriptional profile (ID: GSE28256) and copy number variations (CNV) profile
      were downloaded from Gene Expression Omnibus database. Differentially expressed
      genes (DEGs) between MET proto-oncogene-transformed human primary osteoblast (MET
      HOB) samples and the control samples were identified using the Linear Models for
      Microarray Data package. Subsequently, CNV areas and CNVs were identified using
      cut-off criterion of >30%-overlap within the cases using detect_cnv.pl in
      PennCNV. Genes shared in DEGs and CNVs were obtained and discussed. Additionally,
      the Database for Annotation, Visualization and Integrated Discovery was used to
      identify significant Gene Ontology (GO) functions and pathways in DEGs with
      P<0.05. A total of 1,601 DEGs were screened out in MET-HOBs and compared with
      control samples, including 784 upregulated genes, such as E2F transcription
      factor 1 (E2F1) and 2 (E2F2) and 817 downregulated genes, such as retinoblastoma
      1 (RB1) and cyclin D1 (CCND1). DEGs were enriched in 344 GO terms, such as
      extracellular region part and extracellular matrix and 14 pathways, including
      pathways in cancer and extracellular matrix-receptor interaction. Additionally,
      239 duplications and 439 deletions in 678 genes from 1,313 chromosome regions
      were detected. A total of 12 genes were identified to be CNV-driven genes,
      including cadherin 18, laminin subunit alpha 1, spectrin beta, erythrocytic,
      ciliary rootlet coiled-coil, rootletin pseudogene 2, beta-1,4-N-acetyl
      galactosaminyltransferase 1, G protein regulated inducer of neurite outgrowth 1,
      EH domain binding protein 1-like 1, growth factor independent 1, cathepsin Z, WNK
      lysine deficient protein kinase 1, glutathione S-transferase mu 2 and microsomal
      glutathione S-transferase 1. Therefore, cell cycle-associated genes including
      E2F1, E2F2, RB1 and CCND1, and cell adhesion-associated genes, such as CDH18 and
      LAMA1 may be used as diagnosis and/or therapeutic markers for patients with OS.

PMID- 29207109
TI  - Downregulation of 14-3-3beta inhibits proliferation and migration in osteosarcoma
      cells.
AB  - The 14-3-3 protein isoform beta (14-3-3beta), which is an intracellular adaptor
      protein that exists in all eukaryotic organisms, is highly expressed in many
      cancer tissues, including glioma, lung carcinoma and breast cancer. However, 14-3
      3beta expression and function in osteosarcoma progression remain unknown. In the
      present study, the endogenous expression of 14-3-3beta was assessed in
      osteosarcoma samples and the effect of 14-3-3beta knockdown was examined in human
      osteosarcoma MG63 cells using small interfering RNA (siRNA). mRNA and protein
      expression levels for 14-3-3beta were detected by reverse transcription
      quantitative polymerase reaction and western blotting, respectively. The results
      demonstrated that endogenous 14-3-3beta mRNA and protein were highly expressed in
      human osteosarcoma tissues and osteosarcoma cell lines (U2OS, MG63 and SaOs-2),
      but not in normal bone tissues or normal osteoblast hFOB1.19 cells. These data
      suggested that increased expression of 14-3-3beta may be significantly associated
      with the development and progression of osteosarcoma. Therefore, the effect of 14
      3-3beta knockdown in MG63 cells was further examined in vitro. Knockdown of 14-3
      3beta by siRNA significantly decreased cell viability, and inhibited cell
      proliferation and invasion. In addition, 14-3-3beta knockdown significantly
      decreased the protein expression levels of beta-catenin, cyclin D1, v-myc avian
      myelocytomatosis viral oncogene homolog and matrix metallopeptidase 9 in
      osteosarcoma MG63 cells. These results suggested that the anticancer effects of
      14-3-3beta knockdown in MG63 cells might be mediated by the inhibition of the
      Wnt/beta-catenin signaling pathway. In summary, 14-3-3beta knockdown decreased
      proliferation and invasion in MG63 cells, which suggests a potential therapeutic
      application for 14-3-3beta as a novel target for the treatment of osteosarcoma
      patients.

PMID- 29207110
TI  - Acetylshikonin suppresses invasion of Porphyromonas gingivalis-infected YD10B
      oral cancer cells by modulating the interleukin-8/matrix metalloproteinase axis.
AB  - The development of pharmaceutical agents possessing anti-invasive and anti
      metastatic abilities, as well as apoptotic activity, is important in decreasing
      the incidence and recurrence of oral cancer. Cancer cells are known to acquire
      invasiveness not only through epigenetic changes, but also from inflammatory
      stimuli within the tumor microenvironment. Accordingly, the identification of
      agents that can suppress the inflammation-promoted invasiveness of cancer cells
      may be important in treating cancer and improving the prognosis of patients with
      cancer. Acetylshikonin, a flavonoid with anti-inflammatory activity, inhibits
      proliferation and induces apoptosis of oral cancer cells. In the present study,
      the anti-invasive effect of acetylshikonin on YD10B oral cancer cells infected
      with Porphyromonas gingivalis, a major pathogen of chronic periodontitis, and the
      mechanisms involved were investigated. Firstly, we examined whether P. gingivalis
      infection increased the invasiveness of YD10B cells. Results suggested that YD10B
      oral cancer cells become more aggressive when they are infected with P.
      gingivalis. Secondly, acetylshikonin significantly inhibited the invasion of P.
      gingivalis-infected YD10B cells by suppressing IL-8 release and IL-8-dependent
      MMP release. These data suggest that acetylshikonin may be a useful preventive
      and therapeutic candidate for oral cancer that is chronically infected with
      periodontal pathogens.

PMID- 29207111
TI  - H19 functions as a competing endogenous RNA to regulate human epidermal growth
      factor receptor expression by sequestering let-7c in gastric cancer.
AB  - Long non-coding RNA (lncRNA) H19 has been suggested to serve important roles in
      the progression of gastric cancer (GC); however, the mechanism involved is
      largely unknown. The present study aimed to investigate the mechanism underlying
      the effect of H19 on human epidermal growth factor receptor (HER2) expression.
      Let-7c belongs to the let-7 family, which has been reported to be downregulated
      in cancers and considered to serve as a tumor suppressor. Let-7c has been
      negatively associated with the expression of human epidermal growth factor
      receptor 2 (HER2). Reverse transcription-quantitative polymerase chain reaction
      was used to examine the expression levels of H19 and let-7c in GC tissues and
      cell lines. HER2 protein expression levels were examined using
      immunohistochemistry and western blot analyses. The effect of H19 on let-7c and
      HER2 expression was analyzed following transfection of small interfering RNA
      targeting H19 in GC cells. The results indicated that the expression levels of
      H19 lncRNA in GC tissue samples were significantly higher when compared with that
      in matched benign adjacent tissue samples (P<0.001). H19-silenced GC cells
      exhibited significantly increased let-7c expression and decreased HER2 protein
      expression levels. Assessment of tumor diameter and pathological tumor stage
      suggested that increased H19 expression was associated with a poorer prognosis in
      patients with GC. The results of the present study suggest that H19 may function
      as a competing endogenous RNA to regulate HER2 expression by sequestering let-7c
      in GC cells. The present study has aided the understanding of the mechanism of
      H19 lncRNA in GC, and has provided evidence for the application of lncRNA-based
      diagnostic and therapeutic strategies for GC.

PMID- 29207112
TI  - MicroRNA-381 suppresses the proliferation of osteosarcoma cells through LRH
      1/Wnt/beta-catenin signaling pathway.
AB  - We explored the function of microRNA-381 on osteosarcoma cell growth and
      anticancer mechanism for clinic treatment. MicroRNA-381 of osteosarcoma patients
      was decreased, microRNA-381 levels were more downregulated at stages III/IV than
      those at stage I/II in osteosarcoma patients. Downregulation of microRNA-381
      using anti-microRNA-381 mimics increased cell proliferation, decreased LDH
      activity and apoptosis, and inhibited caspase-3/9 activities, Bax/Bcl-2 and p53
      protein expression in vitro osteosarcoma cells through upregulation of LRH
      1/Wnt/beta-catenin signaling pathway. Overexpression of microRNA-381 using
      microRNA-381 mimics inhibited cell proliferation, induced apoptosis and increased
      LDH activity, caspase-3/9 activities, expression of Bax/Bcl-2 and p53 protein in
      osteosarcoma of in vitro model through downregulation of LRH-1/Wnt/beta-catenin
      signaling pathway. Si-LRH-1 promoted the anticancer effects of microRNA-381 on
      osteosarcoma cell growth through Wnt/beta-catenin signaling pathway. Thus, our
      data suggested that microRNA-381 suppresses the proliferation of osteosarcoma
      cells through upregulation of LRH-1/Wnt/beta-catenin signaling pathway.

PMID- 29207113
TI  - Spontaneous hypothermia ameliorated inflammation and neurologic deficit in rat
      cardiac arrest models following resuscitation.
AB  - Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of
      the associated mortalities are caused by post-CA syndrome, which includes
      symptoms, such as neurologic damage, myocardial dysfunction and systemic
      inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a
      brain reperfusion injury, which subsequently causes adverse neurologic outcomes
      or mortality. Therefore, investigating the underlying mechanisms of ROSC-induced
      neurologic deficits and establishing potential treatments is critical to prevent
      and treat post-CA syndrome. In the current study, CA rat models were established
      by asphyxia. Following ROSC, the temperature was controlled to achieve
      hypothermia. The general neurologic status was assessed using the neurologic
      deficit scale. Changes in the concentrations of interleukin (IL)-18 and IL-1beta
      were measured with ELISA and the dynamic change in NACHT, LRR and PYD domains
      containing protein 3 inflammasome components was determined by western blot
      analysis and immunohistochemistry. Neuronal death and apoptosis were measured via
      TUNEL assays. In the CA rat models, increasing the duration of CA before
      cardiopulmonary resuscitation was found to aggravate the neural deficit and
      increase the incidence of inflammation. Following ROSC, the expression level of
      the inflammasome components was observed to increase in CA rat models, which was
      accompanied by increased secretion of IL-18 and IL-1beta, indicating the
      promotion of inflammation. In addition, the study identified the beneficial role
      of spontaneous hypothermia in ameliorating the ROSC-induced inflammation and
      neurologic deficit in CA rat models, including the downregulation of inflammasome
      components and attenuating neuronal apoptosis. The present study contributes to
      the understanding of underlying mechanisms in CA-evoked inflammation and the
      subsequent neurologic damage following ROSC. A novel potential therapeutic
      strategy that may increase survival times and the quality of life for patients
      suffering from post-CA syndrome is proposed in the present study.

PMID- 29207114
TI  - Elderly apolipoprotein E-/- mice with advanced atherosclerotic lesions in the
      aorta do not develop Alzheimer's disease-like pathologies.
AB  - Atherosclerosis and Alzheimer's disease (AD) are a major cause of morbidity and
      mortality in Western societies. These diseases share common risk factors, which
      are exhibited in old age, including hypertension, diabetes, hypercholesterolemia
      and apolipoprotein (Apo) epsilon4 allele. We previously demonstrated that factor
      XI (FXI) deficiency in mice reduced the atherosclerotic plaque area in coronary
      sinuses and the aortic arch. This led us to investigate whether FXI deficiency in
      elderly ApoE knockout (KO) mice would decrease pathological alterations
      compatible with atherosclerosis and AD. The present study used ApoE/factor XI
      double KO (ApoE/FXI DKO) mice aged 64 weeks and age-matched ApoE KO mice to serve
      as a control group. The ApoE KO mice developed an advanced atherosclerotic lesion
      area in the aortic arch, which was reduced by 33% in the DKO mice. However,
      neither atherosclerosis nor AD-associated pathological alterations in the elderly
      mice brains were observed in either the DKO mice or the ApoE KO mice. The results
      advocate a dichotomy between the brain and peripheral blood vessels. Therefore,
      the ApoE KO and DKO mice cannot serve as mouse models for studying AD or
      pathological brain changes compatible with atherosclerosis. The mechanism by
      which ApoE KO protects against brain pathology should be further studied as it
      may prove helpful for future treatment of senile dementia.

PMID- 29207115
TI  - Current status and future prospects of the strategy of combining CAR-T with PD-1
      blockade for antitumor therapy (Review).
AB  - The immune system serves an important role in controlling and eradicating
      malignant cells. Immunotherapy for treating tumors has received much attention in
      recent years due to its marked effect. There are two approaches which currently
      lead this field: Chimeric antigen receptor-modified T-cell immunotherapy (CAR-T)
      and programmed cell death protein-1 blockade (PD-1 blockade). CAR-T has emerged
      as a promising regimen for the treatment of a range of types of cancer, including
      chronic lymphoid leukemia and neuroblastoma, with studies of long term remission
      in certain patients. PD-1 blockade has been reported to exert marked clinical
      responses in patients against a range of types of solid cancer, including
      advanced melanoma, non-small-cell lung cancer and renal cell carcinoma, in
      addition to hematological malignancies. While increasing the power of the immune
      system to fight cancer has been a long-standing goal in oncology, a number of
      studies have demonstrated the synergistic antitumor effects of combination
      therapies under the umbrella of immunotherapy. The present review focused on a
      novel combination approach involving CAR-T and PD-1 blockade. The present reviews
      aimed to discuss the following four aspects of such an approach: i) Current
      monotherapy status; ii) rationale for the combination of CAR-T and PD-1 blockade;
      iii) current status of the combination of CAR-T and PD-1 blockade; and iv)
      conclusions and future perspectives.

PMID- 29207116
TI  - Melatonin exerts an inhibitory effect on insulin gene transcription via MTNR1B
      and the downstream Raf-1/ERK signaling pathway.
AB  - The pineal hormone melatonin influences the secretion of insulin by pancreatic
      islets via the G-protein-coupled melatonin receptors 1 and 2 that are expressed
      in pancreatic beta-cells. Genome-wide association studies indicate that melatonin
      receptor 1B (MTNR1B) single nucleotide polymorphisms are tightly associated with
      type 2 diabetes mellitus (T2DM). However, the underlying mechanism is unclear.
      Raf-1 serves a critical role in the mitogen-activated protein kinase (MAPK)
      pathways in beta-cell survival and proliferation and, therefore, may be involved
      in the mechanism by which melatonin impacts on T2DM through MTNR1B. In the
      present study, the mRNA expression of the two mouse insulin genes Ins1 and Ins2
      was investigated in MIN6 cells treated with different concentrations of
      melatonin, and insulin secretion was detected under the same conditions.
      Following the overexpression or silencing of MTNR1B, the activities of components
      of the MAPK signaling pathway, including Raf-1 and ERK, were evaluated. The
      impact of MTNR1B knockdown on the melatonin-regulated insulin gene expression and
      insulin secretion were also investigated. The results demonstrated that exogenous
      melatonin inhibited the expression of insulin mRNA in the MIN6 cells. Insulin
      secretion by the MIN6 cells, however, was not affected by melatonin. The MAPK
      signaling pathway was inhibited in MIN6 cells by treatment with melatonin or the
      overexpression of MTNR1B. The knockdown of MTNR1B totally attenuated the
      regulating effect of melatonin on insulin gene expression. Additionally, the
      inductive effect of melatonin on the expression of insulin mRNA was attenuated
      when the activities of Raf-1 or ERK were blocked using the chemical inhibitors
      GW5074 and U0126, respectively. It may be concluded that melatonin exerts an
      inhibitory effect on insulin transcription via MTNR1B and the downstream MAPK
      signaling pathway.

PMID- 29207117
TI  - Clinical significance of CCBE1 expression in lung cancer.
AB  - Lymph node metastasis (LNM) is one of the major causes of cancer-associated
      morbidity and mortality in patients with lung cancer following radical pulmonary
      carcinoma resection. The present study aimed to investigate the relationship
      between the expression of collagen and calcium-binding epidermal growth factor
      domain-containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan
      receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of lung cancer.
      The present study included 40 patients with lung cancer that underwent pulmonary
      carcinoma resection, including 10 patients with LNM, and 10 control patients who
      underwent pulmonary bullae resection. CCBE1 and LYVE1 expression was assessed in
      samples from normal and tumor tissue using polymerase chain reaction, western
      blot analysis and immunohistochemistry. CCBE1 expression appeared to be decreased
      in lung tumor tissue and further downregulated in samples from patients with LNM,
      and was revealed to be correlated with poor clinical outcome. Conversely, LYVE1
      expression appeared to be upregulated in lung cancer tissue. In conclusion, the
      present results suggested that CCBE1 and LYVE1 may have potential as biomarkers
      for the identification of lung cancer patients at a high risk of LNM.

PMID- 29207118
TI  - Oxysophoridine rescues spinal cord injury via anti-inflammatory, anti-oxidative
      stress and anti-apoptosis effects.
AB  - Oxysophoridine (OSR) is an alkaloid extracted from Sophora alopecuroides L and
      has various pharmacological activities. The present study aimed to investigate
      the protective effects and underlying mechanisms of OSR on spinal cord injury
      (SCI), a clinically common serious trauma, in a rat model. The results of the
      present study demonstrated that the anti-inflammatory effect of OSR improved
      Basso, Beatie and Bresnahan Locomotor Rating Scale scores and reduced spinal cord
      tissue water contents in an SCI rat model. Inflammatory activation was measured
      by ELISA, and Prostaglandin E2 (PGE2), intercellular adhesion molecule-1 (ICAM
      1), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and B-cell
      lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax) protein expression levels using
      western blotting. The results revealed that treatment with OSR reduced tumor
      necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8 and malondialdehyde,
      and increased superoxide dismutase and glutathione peroxidase levels in the serum
      of an SCI rat model. OSR significantly reduced the protein expression of
      inflammation-associated proteins PGE2, ICAM-1, COX-2, NF-kappaB and Bcl-2/Bax
      ratio in the spinal cord tissue of an SCI rat model. Furthermore, the results of
      the current study demonstrate that OSR ameliorates SCI via anti-inflammatory,
      anti-oxidative stress and anti-apoptosis effects.

PMID- 29207119
TI  - EZH2 inhibition sensitizes tamoxifen-resistant breast cancer cells through cell
      cycle regulation.
AB  - Enhancer of zeste homologue 2 (EZH2), a catalytic subunit of polycomb repressive
      complex 2, is overexpressed in a number of different tumors including breast
      cancer, and serves important roles in cell cycle regulation, proliferation,
      apoptosis, tumorigenesis and drug resistance. However, it remains unclear whether
      EZH2 contributes to tamoxifen resistance in breast cancer. In the present study,
      the role of EZH2 in tamoxifen resistance in MCF-7 cells was investigated. EZH2
      was overexpressed in MCF-7 tamoxifen-resistant (MCF-7 TamR) cells. EZH2
      overexpression decreased the sensitivity of MCF-7 cells to tamoxifen, and EZH2
      knockdown improved the sensitivity of MCF-7 TamR cells to tamoxifen. Furthermore,
      EZH2 knockdown induced cell cycle arrest in MCF-7 TamR cells, accompanied by a
      decrease in cyclin D1 expression and an increase in p16 expression. EZH2
      knockdown reduced p16 gene methylation in MCF-7 TamR cells. These findings
      suggested that EZH2 overexpression may contribute to tamoxifen resistance in
      breast cancer, and EZH2 inhibition may reverse tamoxifen resistance in breast
      cancer by regulating the cell cycle via the demethylation of the p16 gene. Thus,
      EZH2 inhibitors may be effective for treating tamoxifen resistance in breast
      cancer.

PMID- 29207120
TI  - The antibacterial effect of topical ozone on the treatment of MRSA skin
      infection.
AB  - Skin can be infected by many types of microorganisms, most commonly by gram
      positive strains of Staphylococcus and Streptococcus spp. Treatment of
      Staphylococcus aureus (S. aureus) infections, particularly that of methicillin
      resistant Staphylococcus aureus (MRSA), is a challenge in clinical practice.
      Ozone therapy has proven to be one of the strongest antiseptics against the
      majority of microorganisms involved in skin infections. The purpose of the
      present study was to evaluate the microbicidal effects of topical ozone therapy
      on S. aureus and MRSA, and determine the clinical efficacy of ozone therapy on
      patients with MRSA skin infection. Microbicidal effects of ozonated oil and
      ozonated water were determined by plating and Kirby Bauer methods. Clinical
      efficacy and safety of topical ozone were evaluated in two cases with skin MRSA
      infection. The killing rates of ozonated oil for S. aureus and MRSA were greater
      when compared with the control oil group. Almost 100% of S. aureus were
      eliminated by ozonated oil following 5 min. Almost 100% MRSA were eliminated by
      ozonated oil following 15 min. In addition, 100% S. aureus and 100% MRSA were
      eliminated by ozonated water in 1 min. The inhibition zone diameters of ozonated
      oil for S. aureus and MRSA were 17 and 13 mm, respectively, which were
      significantly larger than the control group. Both cases of skin MRSA infection
      were completely healed with ozone therapy. In conclusion, ozone therapy is a
      potential treatment for S. aureus and MRSA skin infection as it has great
      efficacy, few side effects and low-costs.

PMID- 29207121
TI  - Percentage and function of CD4+CD25+ regulatory T cells in patients with
      hyperthyroidism.
AB  - The current study observed the percentage of peripheral blood (PB) CD4+CD25+
      regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the
      proliferation of naive CD4 T cells in patients with hyperthyroidism. Furthermore,
      preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs
      on hyperthyroidism attacks. The present study identified that compared with the
      percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant
      changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with
      hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs
      exhibited significantly reduced inhibition of the proliferation of naive CD4 T
      cells and decreased secretion capacity on the cytokines of CD4 T cells, compared
      with those of healthy control subjects (P<0.05). In addition, it was demonstrated
      that thyroid function of patients with hyperthyroidism was significantly improved
      (P<0.05) subsequent to receiving medication. Compared with the percentage of PB
      CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant
      changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism
      patients following treatment (P>0.05). In the patients with hyperthyroidism,
      following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition
      of the proliferation of naive CD4 T cells and increased secretion capacity of CD4
      T cell cytokines, compared with those of the patients with hyperthyroidism prior
      to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with
      hyperthyroidism, and its non-proportional decrease may be closely associated with
      the occurrence and progression of hyperthyroidism.

PMID- 29207122
TI  - Diallyl disulfide inhibits the metastasis of type II esophageal-gastric junction
      adenocarcinoma cells via NF-kappaB and PI3K/AKT signaling pathways in vitro.
AB  - Esophageal-gastric junction adenocarcinoma (AEG) is an aggressive tumor with high
      incidence and dismal prognosis worldwide. Despite significant advances in
      therapeutic strategies, the 5-year survival rate still remains low. Diallyl
      disulfide (DADS), which is one of the major volatile components isolated from
      garlic, has been shown to have multi-targeted antitumor activities in a variety
      of cancer cells. However, the exact anti-metastatic effects and underlying
      molecular mechanisms of DADS in AEG have not been elucidated. The present study
      demonstrated that DADS inhibited cell viability of OE19 cells with low
      cytotoxicity to healthy hepatocytes, L02 cells, in vitro. Non-toxic doses of DADS
      were <=10 ug/ml for a 24-h treatment. Our data showed that these non-toxic doses
      of DADS were found to block the metastasis of OE19 cells by suppressing MMPs,
      increasing u-PA and TIMPs, as well as altering the balance of MMPs/TIMPs, which
      at least in part resulted from the suppression of NF-kappaB and PI3K/AKT
      signaling pathways. The present study provides a previously neglected insight
      into the investigation of DADS in suppressing tumor metastasis and its underlying
      molecular mechanisms in vitro. Hence, DADS could be a promising anticancer agent
      for anti-metastatic treatment of AEG in the future.

PMID- 29207123
TI  - NACHT, LRR and PYD domains-containing protein 3 inflammasome is activated and
      inhibited by berberine via toll-like receptor 4/myeloid differentiation primary
      response gene 88/nuclear factor-kappaB pathway, in phorbol 12-myristate 13
      acetate-induced macrophages.
AB  - The nucleotide-binding domain, leucine-rich-containing family, pyrin domain
      containing-3 (NLRP-3) inflammasome has recently emerged as a pivotal regulator of
      chronic inflammation. The present study investigated the expression of NLRP3
      inflammasome in phorbol 12-myristate 13-acetate (PMA)-induced macrophages, and
      aimed to identify the effects of berberine on the inflammasome. Human monocytic
      THP-1 cells were pretreated with berberine for 1 h and then induced with PMA for
      48 h. Total RNA and protein were collected for reverse transcription-quantitative
      polymerase chain reaction and western blot analysis, respectively. Supernatants
      were collected to determine IL-1beta levels by using ELISA. The present study
      demonstrated that NLRP3 inflammasome and IL-1beta were activated in PMA-induced
      macrophages in a time-dependent manner, whereas berberine significantly inhibited
      their expression in a dose-dependent manner in PMA-induced macrophages.
      Furthermore, berberine also suppressed the toll-like receptor 4 (TLR4)/myeloid
      differentiation primary response gene 88 (Myd88)/nuclear factor (NF)-kappaB
      signaling pathway which was activated during the conversion of THP-1 cells to
      macrophages by PMA. In conclusion, berberine reduced NLRP3 inflammasone
      expression by suppressing the activation of the TLR4/Myd88/NF-kappaB signaling
      pathway in PMA-induced macrophages. This inhibitory effect may imply an important
      role of berberine on chronic inflammation and atherogenic progression in coronary
      artery disease.

PMID- 29207124
TI  - Inhibiting proliferation and migration of lung cancer using small interfering RNA
      targeting on Aldo-keto reductase family 1 member B10.
AB  - Lung cancer is the leading cause of global cancer-associated mortality. Genomic
      alterations in lung cancers have not been widely characterized, however, the
      molecular mechanism of tumor initiation and progression remain unknown, and no
      molecularly targeted have been specifically developed for its treatment and
      diagnosis. The present study observed the upregulation of Aldo-keto reductase
      family 1 member Bio10 (AKR1B10) lung cancer tissues by analyzing two public lung
      cancer gene expression datasets. Further experiments in silencing AKR1B10
      demonstrated that the expression of AKR1B10 was associated with cell
      proliferation, cell cycle, adhesion and invasion, as well as extracellular-signal
      regulated kinase/mitogen activated protein kinase signal pathway. The
      overexpression of AKR1B10 in lung cancer indicates the important role of AKR1B10
      in tumorigenesis. These findings suggest that AKR1B10 could be a potential
      diagnosis and treatment mark of lung cancer.

PMID- 29207126
TI  - Melatonin enhances the apoptotic effects and modulates the changes in gene
      expression induced by docetaxel in MCF-7 human breast cancer cells.
AB  - Results from clinical trials and multiple in vivo and in vitro studies point to
      melatonin as a promising adjuvant molecule with many beneficial effects when
      concomitantly administered with chemotherapy. Melatonin palliates side-effects
      and enhances the efficacy of chemotherapeutic agents. However, the mechanisms
      through which melatonin regulates molecular changes induced by chemotherapeutic
      agents remain largely unknown. In this study, we demonstrated that melatonin
      enhanced the anti-proliferative and apoptotic responses to low doses of docetaxel
      in breast cancer cells. Importantly, these effects were more potent when
      melatonin was added prior to docetaxel. Treatment with 1 uM docetaxel (equivalent
      to the therapeutic dosage) induced changes in gene expression profiles and
      melatonin modulated these changes. Specifically, docetaxel downregulated TP53,
      cyclin-dependent kinase inhibitor 1A (CDKN1A) and cadherin 13 (CDH13), and
      upregulated mucin 1 (MUC1), GATA binding protein 3 (GATA3) and c-MYC, whereas
      melatonin counteracted these effects. Melatonin further stimulated the expression
      of the pro-apoptotic BAD and BAX genes, and enhanced the inhibition of the anti
      apoptotic gene BCL-2 induced by docetaxel. The findings of this study suggest
      that melatonin is a molecule with potential for use as an adjuvant in cancer
      chemotherapy, which may have implications for designing clinical trials using
      chemotherapeutic drugs in combination with melatonin.

PMID- 29207127
TI  - Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A
      proof-of-concept study.
AB  - Methotrexate (MTX), as a pharmaceutical, is frequently used in tumor chemotherapy
      and is also a part of the established treatment of a number of autoimmune
      inflammatory disorders. Radiolabeled MTX has been studied as a tumor-diagnostic
      agent in a number of published studies. In the present study, the potential use
      of technetium-99m-labelled MTX (99mTc-MTX) as a radiotracer was investigated for
      the identification of inflammatory target sites. The labelling of MTX was carried
      out via a 99mTc-gluconate precursor. Evaluation studies included in vitro
      stability, plasma protein binding assessment, partition-coefficient estimation,
      in vivo scintigraphic imaging and ex vivo animal experiments in an animal
      inflammation model. MTX was successfully labelled with 99mTc, with a
      radiochemical purity of >95%. Stability was assessed in plasma, where it remained
      intact up to 85% at 4 h post-incubation, while protein binding of the radiotracer
      was observed to be ~50% at 4 h. These preclinical ex vivo and in vivo studies
      indicated that 99mTc-MTX accumulates in inflamed tissue, as well as in the spinal
      cord, joints and bones; all areas with relatively high remodeling activity. The
      results are promising, and set the stage for further work on the development and
      application of 99mTc-MTX as a radiotracer for inflammation associated with
      rheumatoid arthritis.

PMID- 29207128
TI  - NR4A1-induced increase in the sensitivity of a human gastric cancer line to
      TNFalpha-mediated apoptosis is associated with the inhibition of JNK/Parkin
      dependent mitophagy.
AB  - Tumor necrosis factor alpha (TNFalpha)-based immunotherapy is the vital host
      defense system against the progression of gastric cancer (GC) as a pro
      inflammatory and pro-apoptotic cytokine. However, resistance limits its
      therapeutic efficiency. Therefore, an increasing number of studies are focusing
      on the development of drugs or methods with which to enhance the treatment
      efficacy of TNFalpha. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has
      been shown to exert antitumor effects through several mechanisms, such as by
      inhibiting proliferation, as well as pro-apoptotic and potent pro-oxidant
      effects. In this study, we examined the effects and mechanisms of action of NR4A1
      on the apoptosis of GC cells treated with TNFalpha, with particular focus on
      mitochondrial homeostasis. We found that TNFalpha treatment decreased NR4A1
      expression. Moreover, the overexpression of NR4A1 in the presence of TNFalpha
      further increased GC cell apoptosis. Mechanistically, the overexpression of NR4A1
      augmented caspase-9-dependent mitochondrial apoptosis, as evidenced by reduced
      mitochondrial membrane potential, reactive oxygen species (ROS) overproduction,
      mitochondrial permeability transition pore (mPTP) opening and the leakage of
      cytochrome c (Cyt-c) leakage. Moreover, NR4A1 overexpression also evoked
      mitochondrial energy disorder via the suppression of mitochondrial respiratory
      complex expression. Furthermore, we found that TNFalpha treatment activated
      Parkin-dependent mitophagy. Excessive Parkin-dependent mitophagy blocked
      mitochondrial apoptosis, undermining the toxic effects of TNFalpha on cells.
      However, NR4A1 overexpression suppressed Parkin-dependent mitophagy via the
      inhibition of c-Jun N-terminal kinase (JNK). Re-activation of the JNK/Parkin
      pathway abrogated the inhibitory effects of NR4A1 on mitophagy, eventually
      limiting cell apoptosis. Collectively, this study confirmed that NR4A1 sensitizes
      GC cells to TNFalpha-induced apoptosis through the inhibition of JNK/Parkin
      dependent mitophagy.

PMID- 29207125
TI  - The spectrum of myocardial homeostasis mechanisms in the settings of cardiac
      surgery procedures (Review).
AB  - Classic cardiac surgery, determined through the function of cardiopulmonary
      bypass machine and myocardial cardioplegic arrest, represents the most controlled
      scenario for cardiomyocyte homeostatic disturbances due to systemic inflammatory
      response and myocardial reperfusion injury. An increasing number of studies have
      demonstrated that myocardial cell homeostasis in cardiac surgery procedures is a
      sequence of molecularly interrelated and overlapping mechanisms in the form of
      apoptosis, autophagy and necrosis, which are activated by a plethora of induced
      inflammatory mediators and gene-related signaling pathways. In this study, we
      outline the molecular mechanisms of the cardiomyocyte adaptive homeostatic
      process and the associated clinical implications, in the settings of classic
      cardiac surgery procedures.

PMID- 29207129
TI  - Identification of susceptibility loci for thoracic ossification of the posterior
      longitudinal ligament by whole-genome sequencing.
AB  - Ossification of the posterior longitudinal ligament (OPLL) is a myelopathy
      commonly observed in the cervical spine. By contrast, thoracic OPLL (T-OPLL) is
      rare but more severe. Previous studies have identified several polymorphisms in
      osteogenic genes that are associated with the occurrence and development of
      cervical OPLL. However, few genetic studies have evaluated T-OPLL. The present
      study aimed to identify the genetic factors for OPLL by performing whole-genome
      sequencing (WGS) in 30 unrelated northern Chinese Han patients with T-OPLL. Using
      bioinformatics analyses and damaging-variant prediction algorithms, two
      deleterious variants [c.1534G>A(p.Gly512Ser)/collagen, type VI, alpha1 (COL6A1)]
      and [c.2275C>A(p.Leu759Ile)/inteleukin-17 receptor C (IL17RC)] were identified in
      seven unrelated patients. These two mutations resulted in markedly increased gene
      expression levels in peripheral blood samples. To the best of our knowledge, this
      is the first report to describe the use of WGS analysis of T-OPLL in the northern
      Chinese Han population. The results revealed two novel potentially pathogenic
      mutations in patients with T-OPLL.

PMID- 29207130
TI  - Ethanol extract from Cnidium monnieri (L.) Cusson induces cell cycle arrest and
      apoptosis via regulation of the p53-independent pathway in HepG2 and Hep3B
      hepatocellular carcinoma cells.
AB  - Cnidium monnieri (L.) Cusson is a frequently used traditional Chinese medicine
      that treats gynecological diseases and carbuncles. However, the mechanism of
      action of C. monnieri remains to be fully elucidated. The present study examined
      the cell cycle arrest and apoptotic effects resulting from ethanol extract of C.
      monnieri (CME) in HepG2 (wild-type p53) and Hep3B (p53-null) hepatocellular
      carcinoma cells. An MTT assay was used to confirm the anti-proliferative effect
      of CME. The cells were stained with Hoechst 33342 or propidium iodide. It was
      demonstrated that proliferation of HepG2 cells was suppressed by CME. Cell cycle
      arrest occurred in the G1 phase following treatment with CME and the number of
      apoptotic bodies was increased. The expression levels of cell cycle-associated
      proteins, including protein kinase B (Akt), glycogen synthase kinase-3beta (GSK
      3beta), p53, cyclin E and cyclin-dependent kinase 2 (CDK2) were determined by
      western blot analysis. The protein levels of phosphorylated (p)-Akt, p-GSK-3beta,
      p-MDM2 and cyclin E were decreased, whereas the protein levels of p53, p21 and p
      CDK2 (Thr14/Tyr15) were increased following treatment with CME. Furthermore,
      treatment or co-treatment with LY294002 (phosphoinositide-3-kinase/Akt inhibitor)
      or Pifithrin-alpha (p53 inhibitor) with CME resulted in CME-induced G1 arrest
      which occurred through the p53-independent signaling pathway in hepatocellular
      carcinoma cells. In conclusion, CME induces G1 arrest and apoptosis via the
      Akt/GSK-3beta signaling pathway which is regulated by MDM2-induced degradation of
      p21, rather than p53.

PMID- 29207132
TI  - IRF3 signaling pathway serves an important role in poly(I:C)-induced procollagen
      reduction in human skin fibroblasts.
AB  - Pattern recognition receptors (PRRs) are part of the immune system. They can
      recognize pathogen-associated molecular patterns (PAMPs). Toll-like receptors
      (TLRs) and retinoic acid-inducible gene 1 (RIG-1)-like receptors (RLRs) are 2
      types of PRR in the innate immune system. Double-stranded RNA (dsRNA) can exist
      as a PAMP, including dsRNA viruses. dsRNA is known as a ligand not only for TLR3
      but also for RLRs, including melanoma differentiation-associated gene 5 and RIG
      1. Collagen is the main structural protein in the extracellular space in the
      skin. Recently, it was reported that treatment of a synthetic dsRNA, poly(I:C),
      decreases procollagen expression in skin fibroblasts. However, signaling pathways
      involved in this process have not yet been fully elucidated. The present study
      further explored the underlying signaling pathways involved in the processes. It
      was demonstrated by western blotting that treatment of poly(I:C), but not another
      PAMP, Pam3CSK4, inhibited procollagen expression in cultured human skin
      fibroblasts. Treatment of poly(I:C)and Pam3CSK4 induced activation of the mitogen
      activated protein kinases and the nuclear factor-kappaB pathways. However, only
      poly(I:C), but not Pam3CSK4, induced the activation of the interferon regulatory
      factor 3 (IRF3) pathway. By using specific inhibitors, it was demonstrated that
      inhibition of IRF3 pathway relieved poly(I:C)-induced procollagen reduction. In
      conclusion, IRF3 signaling pathway serves an important role in poly(I:C)-induced
      procollagen reduction in skin fibroblasts. This suggests that the IRF3 signaling
      pathway may be a key target for collagen regulation in the skin.

PMID- 29207131
TI  - Lysyl oxidases expression and histopathological changes of the diabetic rat
      nephron.
AB  - Diabetic nephropathy (DN) is a major complication of diabetes, the accumulation
      of extracellular matrix (ECM) is considered an indication of nephropathological
      changes. Lysyl oxidases (LOXs) are also associated with ECM. However, the
      majority of studies on LOXs have focused on their potential role in renal
      fibrogenesis and there has no examination of LOXs expression or the correlation
      with histopathological changes of DN, including glomerular basement membrane
      (GBM) thickening and glomerulosclerosis. In this study, the association between
      histological changes and LOXs was explored using a type 2 diabetes model of male
      Zucker diabetic fatty rats. The expression of LOX and lysyl oxidase-like 1 to 3
      (LOXL1 to 3) levels were evaluated by immunohistochemical staining. The
      expression levels of LOX and LOXL2 in the kidney tissue in the diabetic group
      were significantly higher compared with those of the control group, but LOXL1 and
      LOXL3 expression levels were not significantly different between the two groups.
      These results indicated that LOXL2 and LOX may be critical factors involved in
      the progression of DN.

PMID- 29207133
TI  - Potential role of microRNA-223-3p in the tumorigenesis of hepatocellular
      carcinoma: A comprehensive study based on data mining and bioinformatics.
AB  - The aims of the present study were to examine the potential role of microRNA-233
      3p (miR)-223-3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to
      investigate its diagnostic accuracy and potential molecular mechanisms. The
      expression data of miR-223-3p in HCC were obtained from the Gene Expression
      Omnibus (GEO). Data for the precursor miR-223 were obtained from The Cancer
      Genome Atlas (TCGA). The diagnostic role of miR-223-3p was identified by the
      receiver operating curve (ROC), and the diagnostic value of miR-223-3p in HCC was
      calculated from qualified reports in the literature. In addition, associated data
      from the GEO, TCGA and qualified experiments were pooled for comprehensive meta
      analysis. Genes, which intersected between online prediction databases, natural
      language processing and differentially expressed genes from TCGA were regarded as
      potential targets of miR-223-3p in HCC. The Gene Ontology enrichment analysis and
      the Kyoto Encyclopedia of Genes and Genomes pathways of potential targets were
      performed using the Database for Annotation, Visualization and Integrated
      Discovery. The protein-protein interactions were mapped using the Search Tool for
      the Retrieval of Interacting Genes. Among 15 qualified microarray data sets from
      GEO, seven showed that a significantly lower level of miR-223-3p was present in
      the HCC tissues, compared with that in non-cancerous tissues (P<0.05). In
      addition, five GEO data sets revealed diagnostic values of miR-223-3p, with an
      area under the curve (AUC) of >0.80 (P<0.05). The diagnostic accuracy of the
      precursor miR-223 in TCGA was also calculated (AUC=0.78, P<0.05). Similarly, the
      precursor miR-223 showed a higher level of downregulation in HCC tissues,
      compared with that in healthy controls in TCGA (P<0.001). A summary ROC was also
      calculated as 0.89 (95% CI, 0.85-0.91) in the meta-analysis. A total of 72
      potential targets were extracted, mainly involved in the terms 'microRNAs in
      cancer', 'ATP binding' and 'prostate cancer'. Five potential target genes were
      considered the hub genes of miR-223-3p in HCC, including checkpoint kinase 1, DNA
      methyltransferase 1, baculoviral IAP repeat containing 5, kinesin family member
      23, and collagen, type I, alpha1. Based on TCGA, the hub genes were significantly
      upregulated in HCC (P<0.05). Collectively, these results showed that miR-223-3p
      may be crucial in HCC carcinogenesis showing high diagnostic accuracy, and may be
      mediated by several hub genes.

PMID- 29207134
TI  - Novel herbal medicine LA16001 ameliorates cisplatin-induced anorexia.
AB  - Chemotherapy frequently causes anorexia in cancer patients, which has been
      associated with poor disease prognosis. Several therapeutic strategies for the
      treatment of chemotherapy-induced anorexia are available; however, their adverse
      effects limit their clinical use. Herbal medicines have a long history of use for
      the treatment of various diseases, including cancer, and recent research has
      demonstrated their safety and efficacy. In the present study, combinations of
      herbal medicines were designed based on traditional Korean medicine, and their
      effects were investigated on chemotherapy-induced anorexia. Herbal mixtures were
      extracted, composed of Atractylodes japonica, Angelica gigas, Astragalus
      membranaceus, Lonicera japonica Thunb., Taraxacum platycarpum H. Dahlstedt and
      Prunella vulgaris var. asiatica (Nakai) Hara. The mixtures were termed LCBP
      Anocure-16001-3 (LA16001, LA16002, LA16003). A cisplatin-induced anorexic mouse
      model was used to evaluate the putative effects of the extracts on chemotherapy
      induced anorexia. Treatment with LA16001 was revealed to prevent body weight
      loss, and all three extracts were demonstrated to improve food intake. When the
      molecular mechanisms underlying the orexigenic effects of LA16001 were
      investigated, altered expression levels of ghrelin, leptin and interleukin-6 were
      revealed. Furthermore, LA16001 was reported to induce phosphorylation of Janus
      kinase 1 and signal transducer and activator of transcription 3. In addition,
      LA16001 administration increased the number of white blood cells and neutrophils.
      These results suggested that the herbal formula LA16001 may be able to prevent
      chemotherapy-induced anorexia and may have potential as a novel therapeutic
      strategy for the adjuvant treatment of patients with cancer.

PMID- 29207135
TI  - bFGF promotes Sca-1+ cardiac stem cell migration through activation of the
      PI3K/Akt pathway.
AB  - Cardiac stem cells (CSCs) are important for improving cardiac function following
      myocardial infarction, with CSC migration to infarcted or ischemic myocardium
      important for cardiac regeneration. Strategies to improve cell migration may
      improve the efficiency of myocardial regeneration. Basic fibroblast growth factor
      (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level
      is too low to be effective. The effect of exogenously delivered bFGF on CSC
      migration was observed in vitro and in vivo in the present study. The CSC
      migration index in response to various bFGF concentrations was demonstrated in
      vitro. In addition, a murine myocardial infarction model was constructed and bFGF
      protein expression levels and CSC aggregation following myocardial infarction
      were observed. To study cell migration in vivo, CM-Dil-labeled CSCs or bFGF-CSCs
      were injected into the peri-infarct myocardium following myocardium infarction
      and cell migration and maintenance in the peri-infarct/infarct area was observed
      1 week later. Protein expression levels of bFGF, CXCR-4 and SDF-1 were assessed,
      as was myocardium capillary density. The Akt inhibitor deguelin was used to
      assess the role of the PI3K/Akt pathway in vitro and in vivo. The present study
      demonstrated that bFGF-promoted Sca-1+ CSC migration, with the highest migration
      rate occurring at a concentration of 45 ng/ml. The PI3K/Akt pathway inhibitor
      deguelin attenuated this increase. The phospho-Akt/Akt ratio was elevated
      significantly after 30 min of bFGF exposure. Transplantation of bFGF-treated Sca
      1+ CSCs led to improved cell maintenance in the peri-infarct area and increased
      cell migration to the infarct area, as well as improved angiogenesis. Protein
      expression levels of bFGF, CXCR-4 and SDF-1 were upregulated, and this
      upregulation was partially attenuated by deguelin. Therefore, bFGF was
      demonstrated to promote Sca-1+ CSC migration both in vitro and in vivo, partially
      through activation of the PI3K/Akt pathway. This may provide a new method for
      facilitating CSC therapy for myocardium repair after myocardium injury.

PMID- 29207136
TI  - Exploiting novel valve interstitial cell lines to study calcific aortic valve
      disease.
AB  - Calcific aortic valve disease (CAVD) involves progressive valve leaflet
      thickening and severe calcification, impairing leaflet motion. The in vitro
      calcification of primary rat, human, porcine and bovine aortic valve interstitial
      cells (VICs) is commonly employed to investigate CAVD mechanisms. However, to
      date, no published studies have utilised cell lines to investigate this process.
      The present study has therefore generated and evaluated the calcification
      potential of immortalized cell lines derived from sheep and rat VICs.
      Immortalised sheep (SAVIC) and rat (RAVIC) cell lines were produced by
      transduction with a recombinant lentivirus encoding the Simian virus (SV40) large
      and small T antigens (sheep), or large T antigen only (rat), which expressed
      markers of VICs (vimentin and alpha-smooth muscle actin). Calcification was
      induced in the presence of calcium (Ca; 2.7 mM) in SAVICs (1.9 fold; P<0.001) and
      RAVICs (4.6 fold; P<0.01). Furthermore, a synergistic effect of calcium and
      phosphate was observed (2.7 mM Ca/2.0 mM Pi) on VIC calcification in the two cell
      lines (P<0.001). Analysis of SAVICs revealed significant increases in the mRNA
      expression of two key genes associated with vascular calcification in cells
      cultured under calcifying conditions, runt related transcription factor-2
      (RUNX2;1.3 fold; P<0.05 in 4.5 mM Ca) and sodium-dependent phosphate transporter
      1 (PiT1; 1.2 fold; P<0.05 in 5.4 mM Ca). A concomitant decrease in the expression
      of the calcification inhibitor matrix Gla protein (MGP) was noted at 3.6 mM Ca
      (1.3 fold; P<0.01). Assessment of RAVICs revealed alterations in Runx2, Pit1 and
      Mgp mRNA expression levels (P<0.01). Furthermore, a significant reduction in
      calcification was observed in SAVICs following treatment with established
      calcification inhibitors, pyrophosphate (1.8 fold; P<0.01) and etidronate (3.2
      fold; P<0.01). Overall, the present study demonstrated that the use of
      immortalised sheep and rat VIC cell lines is a convenient and cost effective
      system to investigate CAVD in vitro, and will make a useful contribution to
      increasing current understanding of the pathophysiological process.

PMID- 29207137
TI  - In vitro expression of mutant factor VII proteins and characterization of their
      clinical significance.
AB  - Factor VII (FVII) serves an essential role in the initiation of blood
      coagulation. Mutations in conserved residues within its serine protease domain
      may lead to dysregulated coagulation activity. The objective of the present study
      was to elucidate the impact of altering two conserved residues, H348R and S282R,
      on the functional properties of the FVII protein. The mutation-harboring
      fragments were derived from genomic DNA of a FVII deficient patient. The
      fragments were integrated into a pcDNA vector containing FVII cDNA of HepG2
      cells. The wild-type and mutated FVII constructs were transfected into CHO-K1
      cells as a mammalian cell model. The coagulation activity, antigen levels and
      intracellular localization of the recombinant proteins were studied in
      association with their pathological importance. Results indicated that FVII
      activity was not detectable in conditioned media of the cells transfected with
      the mutated constructs. The H348R mutation reduced the expression of
      intracellular and secreted forms of the FVII protein. Following S282R
      transfection, intracellular FVII expression showed no significant variation;
      however, extracellular protein was reduced. The pattern of intracellular
      localization of mutated FVII remained unaltered in comparison to the wild-type
      protein. In conclusion, the present study suggested that missense mutations
      within the serine protease domain of FVII affect extracellular levels in addition
      to the coagulation activity of FVII. These results may contribute to further
      understanding of the molecular pathogenesis of FVII deficiency and the
      development of pharmaceutical candidates with improved therapeutic properties.

PMID- 29207138
TI  - Anticancer pyridines induce G2/M arrest and apoptosis via p53 and JNK
      upregulation in liver and breast cancer cells.
AB  - In the present study, the synthesis and biological evaluation of one novel
      pyridine and one novel pyridone anticancer compound is reported. The compounds 6
      (2,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-1H-pyridin-2-one (1) and 2
      (2,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)pyridine (2) were synthesized
      from a chalchone precursor. 1 was more active than 2 in inhibiting the
      proliferation of MCF-7 and HepG2 cells, whereas HepG2 cells were more sensitive
      to the antiproliferative activity of these compounds compared with MCF-7 cells.
      The lowest IC50 value was noted for compound 1 in HepG2 cells (IC50=4.5+/-0.3
      uM). The mechanism of action involved induction of G2/M arrest and apoptosis.
      Both 1 and 2 further induced downregulation of the cell cycle-associated protein
      cyclin D1 and upregulation of the cell cycle inhibitors p53 and p21 and the
      apoptosis-associated protein JNK in HepG2 cells. Compound 1 was further shown to
      induce phosphorylation of JNK in HepG2 cells. These results demonstrate promising
      cytostatic effects for the two novel anticancer compounds in human cancer cells.

PMID- 29207139
TI  - CPNE1 silencing inhibits the proliferation, invasion and migration of human
      osteosarcoma cells.
AB  - Osteosarcoma (OS) is the most common primary malignancy of the bone affecting
      children and adolescents. Copine 1 (CPNE1) is a highly conserved calcium
      dependent phospholipid-binding protein and may function in regulating signal
      transduction and membrane trafficking. In the present study, we investigated
      CPNE1 expression in osteosarcoma tissues and cells, and studied the effects of
      small interfering RNA (siRNA)-targeting CPNE1 on proliferation, metastasis and
      chemosensitivity of the osteosarcoma cells. The results demonstrated that CPNE1
      was highly expressed in the osteosarcoma tissues and cell lines. Moreover,
      functional investigations confirmed that CPNE1 knockdown significantly inhibited
      cell proliferation, colony formation, invasion and metastasis in Saos-2 and HOS
      cells. Western blot analysis indicated that CPNE1 silencing downregulated the
      expression of many proteins associated with tumorigenesis and development,
      including Ras, MEK-1/2, WNT1, beta-catenin, cyclin A1, IRAK2 and cIAP2. In
      addition, CPNE1 downregulation enhanced the sensitivity of Saos-2 cells towards
      cisplatin and adriamycin. The present study provides deep insight into the
      clinical use of lentiviral-mediated CPNE1 silencing for osteosarcoma therapy.

PMID- 29207140
TI  - Platelet-rich plasma inhibits RANKL-induced osteoclast differentiation through
      activation of Wnt pathway during bone remodeling.
AB  - Platelet-rich plasma (PRP) is used in the clinic as an autologous blood product
      to stimulate bone regeneration and chondrogenesis. Numerous studies have
      demonstrated that PRP affects bone remodeling by accelerating osteoblast
      formation. With the research perspective focusing on osteoclasts, the present
      study established a mouse model of mandibular advancement to examine the effect
      of PRP on osteoclast differentiation induced by modification of the dynamics of
      the temporomandibular joint (TMJ). The lower incisors of the mice were trimmed by
      1 mm and the resultant change in mandibular position during the process of eating
      induced condylar adaptation to this change. PRP significantly increased the bone
      mass and decreased osteoclastic activity, in vitro as well as in vivo.
      Mechanistically, the reduced expression of receptor activator of nuclear factor
      kappaB ligand (RANKL)-induced differentiation marker genes, including nuclear
      factor of activated T-cells, cytoplasmic 1, c-fos and tartrate-resistant acid
      phosphatase, and that of the resorptive activity marker genes such as cathepsin
      k, carbonic anhydrase 2 and matrix metalloproteinase 9, indicated that PRP
      suppresses RANKL-induced osteoclast differentiation. A microarray analysis
      revealed that several genes associated with the Wnt pathway were differentially
      expressed, which indicated the involvement of this pathway in osteoclast
      differentiation. Furthermore, the activation of the Wnt pathway was verified by
      reverse transcription-quantitative polymerase chain reaction and immunoblot
      analysis of Dickkopf-related protein 1 and beta-catenin. The results of the
      present study indicated that PRP inhibits osteoclast differentiation through
      activation of the Wnt pathway.

PMID- 29207141
TI  - Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and
      enhance proliferation in pancreatic cancer.
AB  - As one of the most aggressive types of tumor, pancreatic cancer is a principal
      cause of tumor-associated mortality. Negative associations between microRNA-29
      (miR-29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be
      associated with the carcinogenesis of a number of types of cancer; however, this
      has not been completely elucidated in pancreatic cancer. In the present study,
      pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15)
      were obtained and the results of reverse transcription-quantitative polymerase
      chain reaction analysis indicated decreased expression of miR-29b and enhanced
      mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the
      corresponding paracancerous tissues. Increased protein expression of DNMT3b was
      demonstrated by western blotting and immunohistochemistry. In addition, the
      negative association between miR-29b and DNMT3b was noted in pancreatic cancer
      tissues, and luciferase reporter assays confirmed that miR-29b was able to
      directly target DNMT3b in vitro. Notably, miR-29b overexpression was able to
      decrease cell viability and to promote the apoptosis by targeting DNMT3b, and the
      knockdown of DNMT3b exhibited consistent results in vitro and in vivo. The
      results of the present study suggested that miR-29b, as a tumor suppressor, may
      be a novel target for the development of treatments for pancreatic cancer.

PMID- 29207142
TI  - Screening and identification of differentially expressed serum proteins in
      patients with vitiligo using two-dimensional gel electrophoresis coupled with
      mass spectrometry.
AB  - In the clinic, vitiligo is characterized by two stages: Stable and progressive.
      The pathogenesis of vitiligo is still not clear. Here, we identified serum
      markers of vitiligo by screening for differentially expressed proteins in
      patients with vitiligo compared to healthy individuals. Serum samples were
      collected from patients with vitiligo (n=10 for both the stable and progressive
      stages) and healthy individuals (n=10). Two-dimensional gel electrophoresis
      followed by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry and western blotting were used to validate the differential
      expression of the proteins in the serum (n=20 each, at both stages for patients
      and healthy individuals). A total of 48 differentially expressed proteins were
      identified by gel image analysis. There were 28 differentially expressed proteins
      in patients with progressive vitiligo (PV) and 13 differentially expressed
      proteins in patients with stable vitiligo (SV) compared with that in healthy
      individuals. Additionally, 7 differentially expressed proteins were identified in
      patients with PV compared with those in patients with SV. The western blotting
      results showed that Peroxiredoxin-6, apolipoprotein L1, apolipoprotein E and
      mannose-binding protein were differentially expressed in patients with different
      stages of vitiligo. Our results showed that change serum levels of several
      proteins might be useful as biomarkers or in understanding the pathogenesis of
      vitiligo.

PMID- 29207143
TI  - Screening and antitumor effect of an anti-CTLA-4 nanobody.
AB  - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of
      immune responses. CTLA-4 is rapidly upregulated following T-cell activation, and
      then binds to B7 molecules with a higher affinity than CD28. CTLA-4 may abolish
      the initiation of the responses of T cells by raising the threshold of signals
      required for full activation of T cells, and it also may terminate ongoing T-cell
      responses. This regulatory role has led to the development of monoclonal
      antibodies (mAbs) designed to block CTLA-4 activity for enhancing immune
      responses against cancer. mAbs have several disadvantages including high
      production cost and unstable behavior. Nanobodies (Nbs) are single-domain antigen
      binding fragments derived from the camelid heavy-chain antibodies, which are
      highly attractive in cancer immunotherapy due to their small size, high
      specificity, and stability. We selected CTLA-4-specific Nbs from a high quality
      dromedary camel immune library by phage display technology. Four positive
      colonies were sequenced and classified based on the amino acids sequences in the
      CDR3 region. These Nbs recognized unique epitopes on CTLA-4 and displayed high
      binding rates when used on PHA-stimulated human T cells. Treatment of B16
      melanoma-bearing C57BL/6 mice with anti-CTLA-4 nanobody 16 (Nb16) delayed
      melanoma growth and prolonged the survival time of mice. These data indicate that
      anti-CTLA-4 Nbs selected from a high quality phage display library may be
      effective for the treatment of patients with tumors.

PMID- 29207144
TI  - DNER modulates the length, polarity and synaptogenesis of spiral ganglion neurons
      via the Notch signaling pathway.
AB  - The Delta/Notch-like epidermal growth factor-related receptor (DNER) serves an
      important role in the developing central nervous system. However, the actions of
      DNER in the development of the spiral ganglion in the inner ear have yet to be
      elucidated. Wild-type C57BL/6 mice were housed and time-mated for use in the
      present study. Primary neuronal cultures were prepared using spiral ganglion
      progenitors isolated from the modiolus of postnatal day 1 (P1) mice. DNER
      recombinant lentiviral vectors were constructed and transfected into the cultured
      primary neurons. The relative proportion of differentiated neurons and the length
      of their neurites were evaluated using microscopy. The results of the present
      study demonstrated that DNER was expressed in spiral ganglion neurons (SGNs) that
      exhibited significant polarity in the early differentiation stages; DNER
      expression gradually decreased until the polarity was lost on week 35. The in
      vitro expression of DNER was revealed to be similar to that in vivo. When DNER
      expression was silenced using RNA interference, the polarity of the
      differentiated neurons was altered and they exhibited significantly reduced
      dendritic length. In addition, the proportion of bipolar neurons was decreased
      compared with the control group. Furthermore, the expression of alpha-synuclein
      and the GluR2/3 subunits of the alpha-amin-o-3-hydroxy-5-methyl-4
      isoxazolepropionic acid glutamate receptor were also reduced in cultured neurons
      in which DNER was silenced. Notch1 was co-expressed with DNER in SGNs isolated
      from P1 mice. The indirect Notch inhibitor N-[N-(3,5-Difluorophenacetyl)-L
      alanyl]-S-phenylglycine t-butyl ester also affected the polarity and the
      formation of protrusions, and reduced the expression of DNER and glial fibrillary
      acidic protein in SGNs. In conclusion, the present study demonstrated that DNER
      was expressed in SGNs and appeared to be involved in the mechanisms underlying
      neuronal polarity and neuritogenesis, via a Notch-dependent signaling pathway.

PMID- 29207145
TI  - MicroRNA-133a acts as a tumour suppressor in breast cancer through targeting
      LASP1.
AB  - Many microRNAs (miRs) have been demonstrated to play promoting or tumor
      suppressive roles in human cancers including breast cancer. However, the
      molecular mechanism of miR-133a underlying the malignant progression of breast
      cancer still remains obscure. In the present study we observed that the
      expression of miR-133a was significantly downregulated in breast cancer tissues
      and cell lines, when compared with adjacent non-tumor tissues and normal breast
      cell line, respectively. Reduced miR-133a levels were significantly associated
      with advanced clinical stage, lymph node metastasis, as well as shorter survival
      time of patients with breast cancer. Restoration of miR-133a expression led to
      significant decrease in the proliferation, migration, and invasion of SK-BR-3 and
      MDA-MB-231 cells in vitro, as well as in tumor xenograft growth in nude mice.
      Luciferase reporter gene assay data identified LASP1 as a target gene of miR
      133a, and the expression of LASP1 was negatively regulated by miR-133a in breast
      cancer cells. LASP1 was significantly upregulated in breast cancer tissues and
      cell lines, and its upregulation was significantly associated with disease
      progression. siRNA-induced LASP1 downregulation caused a significant reduction in
      breast cancer cell proliferation, migration and invasion. Furthermore,
      overexpression of LASP1 impaired the suppressive effects of miR-133a upregulation
      on the proliferation, migration and invasion of SK-BR-3 and MDA-MB-231 cells. In
      summary, the present study demonstrates that miR-133a acts as a tumor suppressor
      in breast cancer partly at least via targeting LASP1, and thus suggests that the
      miR-133a/LASP1 axis may become a potential therapeutic target for breast cancer.

PMID- 29207146
TI  - Interference of Notch 1 inhibits the proliferation and invasion of breast cancer
      cells: Involvement of the beta-catenin signaling pathway.
AB  - Breast cancer is one of the most common types of carcinoma in humans. The aim of
      the present study was to identify the role of Notch 1 in the proliferation and
      invasion of human breast cancer cells. Firstly, the levels of Notch 1 were
      determined by western blot analysis in breast cancer cell lines, and the results
      revealed that the expression levels of Notch 1 were markedly higher in MDA-MB-231
      and MCF-7 cells, and lower in MCF-10A cells, compared with human mammary
      epithelial cells. An MTT assay was used to determine the viability of breast
      cancer cells. The optical density (OD)490 values were significantly decreased in
      Notch 1 short hairpin (sh)RNA-transfected MCF-7 and MDA-MB-231 cells, compared
      with the OD490 values in the negative control shRNA-transfected cells. The MCF-7
      cells and MDA-MB-231 cells were also treated with increasing concentrations of
      MRK003, a Notch 1 inhibitor, for 24, 48 and 72 h, respectively. The inhibition
      rate was gradually increased in the MRK003-treated cells in a time- and dose
      dependent manner. The invasive ability of the cells was determined using a
      Transwell migration assay. The migration ability was significantly decreased in
      the Notch 1-transfected MCF-7 cells and MDA-MB-231 cells. The molecular mechanism
      was examined, and the knockdown of Notch 1 significantly decreased the expression
      levels of beta-catenin, matrix metalloproteinase (MMP)-2 and MMP-9, and was also
      correlated with the downregulation of beta-catenin in the nucleus. In conclusion,
      Notch 1 was key in the progression of breast cancer, and knocking down the
      expression of Notch 1 significantly suppressed the proliferation and invasion of
      breast cancer cells. This provides novel clues for cancer therapy in human breast
      cancer.

PMID- 29207147
TI  - Effect and mechanism of RNAi targeting WWTR1 on biological activity of gastric
      cancer cells SGC7901.
AB  - Gastric cancer (GC) is one of the most common malignancies in the world. It is
      essential to develop novel targets and therapeutic approaches for GC, which
      requires identification of novel functional molecules. WW-domain containing
      transcription regulator 1 (WWTR1) may activate many transcriptional factors and
      exhibit an important role in the development of various tissues in mammals. The
      results of the present study demonstrated that mRNA and protein levels of WWTR1
      are increased in GC tissues and cell lines. The SGC7901 cell line was selected to
      perform RNA interference (RNAi) targeting WWTR1, and for subsequent study.
      Compared with control groups (cells without any treatment) and mock groups (cells
      treated with nonspecific siRNA), cell proliferation of siWWTR1 cells (cells
      treated with WWTR1 siRNA) was detected using a Cell Counting Kit-8 assay at 12,
      24 and 48 h, and decreased in a time-dependent manner. Cell cycle and apoptosis
      status were determined by flow cytometry, and it was demonstrated that G1/S
      transition was blocked in the cell cycle and apoptosis promoted in siWWTR1 cells,
      compared with control and mock cells. Reverse transcription-quantitative
      polymerase chain reaction and western blotting were performed to detect the mRNA
      and protein levels of cell cycle and apoptosis-associated factors. The expression
      of Cyclin D1, cancer Myc and B cell lymphoma/leukemia-2 (Bcl-2) decreased and Bcl
      2 associated X protein increased significantly in siWWRT1 cells, at the mRNA and
      protein level, compared with control and mock cells. With the exception of the
      Hippo pathway, siWWTR1 regulated downstream factors, including mothers against
      decapentaplegic homolog family member 3 (SMAD3) and inhibitor of DNA binding 1,
      HLH protein (ID1), HLH protein in the transforming growth factor (TGF)-beta
      pathway. The expression of asparagine synthetase was decreased whereas ID1, SMAD3
      (proteins that participate in intracellular TGF-beta transduction) and
      betacellulin increased notably in siWWRT1 cells. In conclusion, WWTR1 promotes
      cell proliferation and inhibits apoptosis of GC cells by regulating cell
      cycle/apoptosis-associated factors, and effectors in the TGF-beta pathway.

PMID- 29207148
TI  - Paeoniflorin inhibits PDGF-BB-induced human airway smooth muscle cell growth and
      migration.
AB  - Abnormal proliferation and migration of airway smooth muscle cells (ASMCs) is
      important in the progression of asthma. Paeoniflorin (PF), one of the major
      active ingredients of Paeonia lactiflora, has been reported to exhibit anti
      asthmatic effects. However, the effects of PF in the regulation of platelet
      derived growth factor (PDGF)-BB-induced ASMC proliferation and migration remain
      unknown. The present study was designed to investigate the effects of PF on human
      ASMCs and the underlying mechanism. The results demonstrated that PF treatment
      significantly reduced the numbers of live ASMC cells and their PDGF-BB-induced
      migration. PF treatment also suppressed PDGF-BB-induced alpha-smooth muscle actin
      expression in ASMCs. Furthermore, pretreatment with PF reduced PDGF-BB-induced
      phosphorylation of phosphoinositide 3-kinase (PI3K) and AKT serine/threonine
      kinase 1 (Akt) in ASMCs. In conclusion, the present study demonstrated for the
      first time that PF inhibited ASMC growth and migration induced by PDGF-BB, and
      that this effect may be partly due to inhibition of the PI3K/Akt signaling
      pathway. The results provide novel information regarding the role of PF as a
      potential therapeutic agent for the treatment of asthma.

PMID- 29207149
TI  - Knockdown of Trio by CRISPR/Cas9 suppresses migration and invasion of cervical
      cancer cells.
AB  - Triple functional domain protein (Trio) is an evolutionarily conserved protein
      with guanine nucleotide exchange factors that regulate different physiological
      processes in some types of cancer. However, the expression and function of Trio
      in cervical cancer are still unknown. The purpose of this study was to detect the
      expression of Trio in cervical cancer tissues and to evaluate its clinical value.
      Furthermore, the effects of the Trio on the migration and invasion of cervical
      cancer cells and its mechanism were investigated in vitro. The results of the
      present study revealed that Trio expression levels were significantly higher in
      most of the clinical cervical cancer samples than in adjacent tissues. The
      clinicopathological significance of Trio expression was also analyzed, and the
      results revealed that high expression levels in cervical cancer were correlated
      with lymph node metastasis (P=0.005). The CRISPR/Cas9 system was used to
      knockdown the endogenous Trio. The inhibition of Trio significantly decreased the
      migration and invasion abilities of cervical cancer cells. Meanwhile, levels of
      RhoA/ROCK signaling factors (RhoA, Rock, and p-LIMK), which contributed to cell
      migration and invasion, were decreased along with the inhibition of Trio.
      Therefore, Trio may regulate the migration and invasion of cervical cancer
      through the RhoA/ROCK signaling pathway.

PMID- 29207150
TI  - Inhibition of autophagy enhances the targeted therapeutic effect of sorafenib in
      thyroid cancer.
AB  - The multi-target kinase inhibitor sorafenib has been approved for the treatment
      of patients with advanced differentiated thyroid cancer. However, different
      sensitivities to sorafenib have been observed, and few patients have benefited
      from sorafenib treatment in the long term. In the event of acquired resistance to
      sorafenib it is not beneficial to continue treatment in most patients. Autophagy
      can be induced in a variety of cancer treatments and plays an important role in
      cancer treatment. The role of autophagy in sorafenib treatment of thyroid cancer
      has not been fully demonstrated. The present study investigated whether autophagy
      is activated by sorafenib during the treatment of thyroid cancer, examined the
      underlying mechanisms, and explored potential strategies to enhance the
      therapeutic sensitivity of sorafenib. Chloroquine (CQ) is an autophagy inhibitor
      that has been reported to increase sensitivity to various cancer treatments.
      Thyroid cancer xenograft model mice were treated with sorafenib, CQ, or a
      combination of sorafenib and CQ. We observed that CQ or sorafenib treatment
      suppressed tumor growth, while mice treated with the combination of sorafenib and
      CQ displayed significantly reduced tumor growth compared with those treated with
      sorafenib or CQ alone. Western blotting results indicated that sorafenib
      concurrently inhibited the activities of the MAPK and AKT/mTOR pathways in
      thyroid cancer. Autophagy was activated by sorafenib in thyroid cancer, both in
      vitro and in vivo, which was at least in part due to suppression of the AKT/mTOR
      pathway. Combination treatment including CQ could inhibit the autophagic flux
      induced by sorafenib. Silencing the key autophagy gene ATG5 using small
      interfering RNA also increased the anticancer effect of sorafenib. In summary,
      the present study revealed that inhibition of autophagy enhances the anticancer
      effect of sorafenib, and the combination of CQ with sorafenib treatment
      represents a potential therapeutic strategy for treating advanced differentiated
      thyroid cancer.

PMID- 29207151
TI  - Long non-coding nuclear paraspeckle assembly transcript 1 acts as prognosis
      biomarker and increases cell growth and invasion in cervical cancer by
      sequestering microRNA-101.
AB  - Emerging studies have focused on the essential role of long non-coding RNAs
      (lncRNAs) in cervical carcinogenesis. A recent study has indicated that nuclear
      paraspeckle assembly transcript 1 (NEAT1) is highly expressed in the human
      cervical tissue. However, whether NEAT1 is involved in cervical cancer remains to
      be elucidated. Reverse transcription-quantitative polymerase chain reaction
      results demonstrated that the expression of NEAT1 was higher in cervical cancer
      cells/tissues compared with that in normal human keratinocytes/tissues. Patients
      with higher NEAT1 level had poorer clinical characteristics and a shorter
      survival time compared with those that exhibited lower NEAT1 expression levels.
      In vitro, flow cytometery analysis revealed that transfection with NEAT1 small
      interfering RNA retarded cervical cancer cell (Caski and HeLa) growth by
      decreasing the percentage of S phase in the cell cycle and inducing cell
      apoptosis. In addition, the colony formation assay, wound healing assay and
      matrigel invasion assay results indicated that downregulation of NEAT1 inhibited
      colony formation, cell migration and invasion. Further investigation using the
      luciferase reporter assay revealed that the expression of mircoRNA-101 (miR-101)
      target gene Fos was positively associated with NEAT1 expression due to NEAT1
      competitive molecular sequestering of miR-101 via base pairing. Furthermore,
      reduction of miR-101 expression by inhibitor transfection reversed the effect of
      NEAT1 siRNA on cervical cancer cells. To conclude, the present data indicated
      that NEAT1 promoted cervical cancer progression by targeting miR-101.

PMID- 29207152
TI  - Increased soluble ST2 and IL-4 serum levels are associated with disease severity
      in patients with membranous nephropathy.
AB  - The interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis regulates Th2
      reactivity, and ST2 is the receptor for IL-33. In this study, the roles of IL-33
      and soluble ST2 (sST2) in the pathogenesis of membranous nephropathy (MN), and
      their association with disease severity were evaluated. Serum levels of IL-33 and
      sST2 in 93 patients, and 34 healthy controls (HCs) were measured by enzyme-linked
      immunosorbent assays. Clinical characteristics were recorded and the estimated
      glomerular filtration rates (eGFRs) were computed. In addition, the association
      between serum IL-33 and sST2 levels, and clinical measurements in patients with
      MN was analyzed. No difference in the serum levels of IL-33 was identified
      between the patients with MN and HCs. However, the serum levels of sST2 were
      considerably higher in the MN patients compared with in the HCs at every stage.
      Higher concentrations of serum IL-2, IL-4, IL-10, IL-17A, and IFN-gamma were
      measured in the MN patients compared with in the HCs. Serum sST2 concentrations
      were negatively correlated with IL-4 concentrations in the patients with MN.
      Furthermore, serum sST2 levels were negatively correlated with the eGFRs and
      serum calcium levels. Serum sST2 levels, but not IL-33 levels, were positively
      correlated with the 24-h urine protein and serum phosphorus levels. Following
      treatment, serum sST2 levels were considerably reduced, whereas serum IL-4 and IL
      10 levels were significantly increased. These data suggest that sST2 and IL-4,
      but not IL-33, contribute to the pathogenesis of MN.

PMID- 29207153
TI  - FGFR inhibitor BGJ398 and HDAC inhibitor OBP-801 synergistically inhibit cell
      growth and induce apoptosis in bladder cancer cells.
AB  - In advanced bladder cancer, cisplatin-based chemotherapy has been the standard
      treatment for many years, but there are many problems in terms of side-effects.
      Recently, a number of clinical trials using molecular-targeted agents have been
      conducted, and new therapies are expected that could replace conventional
      cytotoxic chemotherapy. We herein report that concurrent treatment with
      fibroblast growth factor receptor (FGFR) inhibitor BGJ398 and the novel histone
      deacetylase (HDAC) inhibitor OBP-801/YM753/spiruchostatin A synergistically
      inhibited cell growth and markedly induced apoptosis in high-grade bladder cancer
      cells. This combination activated caspase-3, -8 and -9, and the pan-caspase
      inhibitor zVAD-fmk significantly reduced the apoptotic response to the combined
      treatment. The combination upregulated the expression of Bim, one of the pro
      apoptotic molecules. In the present study, Bim siRNA efficiently reduced
      apoptosis induced by the co-treatment of BGJ398 and OBP-801. Therefore, the
      apoptosis induced by the combination was shown to be at least partially dependent
      on Bim. Taken together, these results suggest that the combination of BGJ398 and
      OBP-801 is a novel high potential therapeutic strategy for muscle-invasive
      bladder cancer.

PMID- 29207154
TI  - Adipose-derived stem cell conditioned medium attenuates cisplatin-triggered
      apoptosis in tongue squamous cell carcinoma.
AB  - Autologous fat grafting procedures have noted a markedly increased frequency, not
      only for cosmetic purposes, but also for deformities after head and neck cancer
      and breast cancer surgery. Carcinogenesis is always a major concern in cell
      therapy-related issues. However, there is no literature discussing this issue in
      head and neck squamous cell carcinoma patients. To evaluate the interaction of
      tongue cancer cells and adipose-derived stem cells, we performed a series of in
      vitro experiments. Our results demonstrated that cisplatin significantly reduced
      the viabilities of SCC-25 and CAL-27 cells in a concentration-dependent manner,
      but it had low cytotoxicity in cisplatin-resistant CAL-27 (CAR) cells. There was
      no significant difference in terms of viability among the SCC-25, CAL-27, and CAR
      cells in the adipose-derived stem cell conditioned medium and control groups.
      There was also no significant difference in terms of cell migration as determined
      by wound healing assay of SCC-25, CAL-27, and CAR cells between the adipose
      derived stem cell conditioned medium treatment and control treatment.
      Importantly, the adipose-derived stem cell conditioned medium attenuated
      cisplatin-triggered cell death in the SCC-25 and CAL-27 cells. Moreover, adipose
      derived stem cell conditioned medium markedly inhibited cisplatin-induced
      apoptotic cell death (sub-G1 phase) in the CAL-27 cells. Western blot analyses
      indicated that cisplatin-induced reductions in pro-caspase-3, pro-caspase-9,
      phospho-BAD, phospho-IGF-1R, phospho-AKT, and phospho-ERK in CAL-27 cells were
      reversed by adipose-derived stem cell conditioned medium supplement. Taken
      together, we provide evidence that adipose-derived stem cell conditioned medium
      protects CAL-27 cells from cisplatin-induced cell death, possibly through
      upregulation of the IGF-1R/AKT/ERK signaling pathway.

PMID- 29207155
TI  - miRNA-27a promotes the proliferation and inhibits apoptosis of human pancreatic
      cancer cells by Wnt/beta-catenin pathway.
AB  - A specific expression of miRNA in pancreatic cancer renders it the novel
      diagnostic marker of pancreatic cancer. Therefore, we investigated how the
      anticancer effect of miRNA-27a suppressed cell growth and induced apoptosis of
      human pancreatic cancer cells. We upregulated miRNA-27a expression in PANC-1
      cells using miRNA-27a mimic, which demonstrated that induction of cell growth and
      suppression of apoptosis of human pancreatic cancer cells were observed. However,
      anti-miRNA-27a inhibited cell growth and apoptosis in pancreatic cancer cells.
      The downregulation of miRNA-27a suppressed Wnt/beta-catenin pathway. The
      inhibition of Wnt/beta-catenin pathway increased the anticancer effects of anti
      miRNA-27a on human pancreatic cancer cells. Taken together, miRNA-27a promotes
      the proliferation and inhibits apoptosis of human pancreatic cancer cells via
      Wnt/beta-catenin pathway.

PMID- 29207156
TI  - MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in
      H2O2-treated lung cancer cells via increased superoxide anion and glutathione
      depletion.
AB  - Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), induce
      apoptosis in cancer cells by regulating mitogen-activated protein kinase (MAPK)
      signaling pathways. The present study investigated the effects of MAPK inhibitors
      on cell growth and death as well as changes in ROS and glutathione (GSH) levels
      in H2O2-treated Calu-6 and A549 lung cancer cells. H2O2 inhibited growth and
      induced death of Calu-6 and A549 lung cancer cells. All MAPK inhibitors appeared
      to enhance growth inhibition in H2O2-treated Calu-6 and A549 lung cancer cells
      and increased the percentage of Annexin V-FITC-positive cells in these cancer
      cells. Among the MAPK inhibitors, a JNK inhibitor significantly augmented the
      loss of mitochondrial membrane potential (MMP; DeltaPsim) in H2O2-treated Calu-6
      and A549 lung cancer cells. Intracellular ROS levels were significantly increased
      in the H2O2-treated cells at 1 and 24 h. Only the JNK inhibitor increased ROS
      levels in the H2O2-treated cells at 1 h and all MAPK inhibitors raised superoxide
      anion levels in these cells at 24 h. In addition, H2O2 induced GSH depletion in
      Calu-6 and A549 cells and the JNK inhibitor significantly enhanced GSH depletion
      in H2O2-treated cells. Each of the MAPK inhibitors altered ROS and GSH levels
      differently in the Calu-6 and A549 control cells. In conclusion, H2O2 induced
      growth inhibition and death in lung cancer cells through oxidative stress and
      depletion of GSH. The enhanced effect of MAPK inhibitors, especially the JNK
      inhibitor, on cell death in H2O2-treated lung cancer cells was correlated with
      increased O2*- levels and GSH depletion.

PMID- 29207157
TI  - Microarray analysis reveals gene and microRNA signatures in diabetic kidney
      disease.
AB  - The current study aimed to identify therapeutic gene and microRNA (miRNA)
      biomarkers for diabetic kidney disease (DKD). The public expression profile
      GSE30122 was used. Following data preprocessing, the limma package was used to
      select differentially-expressed genes (DEGs) in DKD glomeruli samples and tubuli
      samples and they were compared with corresponding controls. Then overlapping DEGs
      in glomeruli and tubuli were identified and enriched analysis was performed. In
      addition, protein-protein interaction (PPI) network analysis as well as sub
      network analysis was conducted. miRNAs of the overlapping DEGs were investigated
      using WebGestal. A total of 139 upregulated and 28 downregulated overlapping DEGs
      were selected, which were primarily associated with pathways involved in
      extracellular matrix (ECM)-receptor interactions and cytokine-cytokine receptor
      interactions. CD44, fibronectin 1, C-C motif chemokine ligand 5 and C-X-C motif
      chemokine receptor 4 were four primary nodes in the PPI network. miRNA (miR)-17
      5p, miR-20a and miR-106a were important and nuclear receptor subfamily 4 group A
      member 3 (NR4A3), protein tyrosine phosphatase, receptor type O (PTPRO) and
      Kruppel like factor 9 (KLF9) were all predicted as target genes of the three
      miRNAs in the integrated miRNA-target network. Several genes were identified in
      DKD, which may be involved in pathways such as ECM-receptor interaction and
      cytokine-cytokine receptor interaction. Three miRNAs may also be used as
      biomarkers for therapy of DKD, including miR-17-5p, miR-20a and miR-106a, with
      the predicted targets of NR4A3, PTPRO and KLF9.

PMID- 29207158
TI  - Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing
      KRAS expression.
AB  - The microRNA miR-19a is closely related to tumor formation and development and is
      a key oncogene. Previous studies have demonstrated that miR-19a is upregulated in
      multiple cancer types, including colorectal cancer (CRC). However, most of these
      experiments were performed in vitro, and consequently, the mechanisms underlying
      the effects of miR-19a on CRC are still unclear. Therefore, in the present study,
      we investigated the role of miR-19a in the development of solid CRC tumors. We
      generated KRAS 3'UTR-Mut by deleting the predicted binding site for miR-19a in
      KRAS, and observed that the expression of a reporter gene containing the KRAS
      3'UTR in HCT116 cells was suppressed by miR-19a, while that of a reporter gene
      with mutant KRAS 3'UTR was unaffected by miR-19a. We observed that high miR-19a
      levels reduced KRAS expression. In the tube formation assay, overexpression of
      miR-19a exhibited anti-angiogenesis effects, which were rescued by KRAS
      expression. We established a nude mouse xenograft model to investigate the
      specific role of miR-19a in solid tumors. The results revealed that the sizes of
      xenograft tumors and density of blood vessels developed from HCT116 cells
      expressing miR-19a were smaller/lower compared with those of the control. KRAS
      and VEGFA levels were also reduced. In conclusion, our results revealed that miR
      19a overexpression supressed KRAS expression and angiogenesis in CRC, indicating
      possibilities of using miR-19a in future therapeutic applications.

PMID- 29207159
TI  - Downregulation of miR-146a promotes proliferation and migration of AOB-treated
      embryoid body via PDGFRA induction.
AB  - Antioxidant of bamboo leaves (AOB) has been proven to have antioxidant activity
      and an inhibitory effect on free radicals that induce deterioration of
      macromolecules. The multi-target regulation of microRNAs (miRs) in the
      complicated process of vasculogenesis and angiogenesis lead to the use of miRNA
      therapy in vascular development. In the present study, the role of miRNAs on
      early embryo vascular development upon AOB stimulation was investigated. For this
      purpose, mouse embryonic stem cells were spontaneously differentiated as embryoid
      bodies (EBs) and were examined by phase contrast microscopy. miR-146a mimic and
      scramble control were transfected into EBs and potential targets of miR-146a were
      predicted. Cell proliferation and migration were detected by cell viability and
      wound-healing and migration assays, respectively. Angiogenesis was determined by
      the Spheroid sprouting assay. It was demonstrated that EBs transfected with miR
      146a mimic had an increased growth rate compared with the control cells. miR-146a
      transfected cells were very susceptible to AOB treatment. Furthermore, among the
      predicted miR-146a targets, platelet-derived growth factor receptor alpha
      (PDGFRA) was identified as a bona fide target of miR-146a. In conclusion, PDGFRA
      was demonstrated to participate in the modulation of cell migration and
      proliferation of mouse EBs. The present study expanded the current understanding
      of AOB biology and elucidated the mechanisms underlying early embryo vascular
      development upon AOB stimulation.

PMID- 29207160
TI  - UNC0638, a G9a inhibitor, suppresses epithelial-mesenchymal transition-mediated
      cellular migration and invasion in triple negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is associated with an aggressive clinical
      history, high risk of recurrence and metastasis, and shorter patient survival due
      to lack of targeted therapy. In the present study, UNC0638, a chemical G9a
      inhibitor, was identified to suppress TNBC cell invasion and migration in vitro
      at a non-cytotoxic concentration. In addition, UNC0638 reduced the size and
      number of the tumorsphere and decreased anchor-independent colony formation in
      the two TNBC cell lines. Evaluation of the underlying mechanism revealed that the
      suppressive effect of UNC0638 is associated with modulation of epithelial
      mesenchymal transition through enhancing E-cadherin promoter activities and
      restoring its expression. Thus, the current data indicates that UNC0638 may be
      developed as a chemotherapeutic agent to effectively treat metastatic cancers,
      including TNBC.

PMID- 29207161
TI  - Inhibition of autophagy in hepatocarcinoma cells promotes chemotherapeutic agent
      induced apoptosis during nutrient deprivation.
AB  - Autophagy is a lysosome-dependent process involved in protein and organelle
      degradation. It has been suggested that autophagy is activated in nutrient
      deficient condition and plays an important role in protecting cells from nutrient
      shortage. However, the effect of autophagy on chemotherapy during nutrient
      deficiency has been rarely researched. In the present study, we discovered that
      hepatocarcinoma cells exhibit chemoinsensitivity accompanied by the activation of
      autophagy when cultured in nutrient-deprived medium. Inhibition of autophagy by 3
      methyladenine or siRNA-targeted Beclin 1 increased the nutrient deprivation
      induced apoptosis and chemosensitivity in hepatocarcinoma cells. Furthermore,
      decreased mitochondrial mass was detected when cells underwent autophagy. The
      present study suggests that induction of autophagy confers a survival advantage
      for hepatocarcinoma cells during nutrient deprivation, not only rescuing cells
      from nutrient deficiency-induced cell apoptosis, but also protecting cells from
      chemotherapy-induced cell death. Combined usage of the inhibition of autophagy
      and conventional chemotherapeutic agents could be an effective therapy for
      hepatocarcinoma during nutrient deprivation.

PMID- 29207162
TI  - miR-33a hinders the differentiation of adipose mesenchymal stem cells towards
      urothelial cells in an inductive condition by targeting beta-catenin and TGFR.
AB  - Tissue engineering technology offers an appealing approach for tissue
      reconstruction of the urothelium. Adipose-derived mesenchymal stem cells (ADSCs)
      represent an abundant source for tissue engineering applications. However, ASCs
      primarily possess mesoderm lineage differentiation potential. It is difficult to
      induce differentiation of ASCs towards urothelial cells that are derived from the
      endoderm, although a recent findings have reported that a conditioned medium may
      drive ADSCs towards differentiation into the urothelium phenotype. In the present
      study, human ADSCs were isolated from abdominal adipose tissues and incubated in
      this conditioned medium for indicated time periods. Western blotting showed that
      protein expression levels of urothelial specific marks, including CK7, CK20 and
      UPIII, were increased after seven days' incubation, but immunofluorescence
      microscopy determined that cells with CK7 and UPIII staining were scarce, which
      suggested a low-efficiency for the differentiation. Prolonging the incubation
      time did not further increase CK20 and UPIII expression. Furthermore, miR-33a
      expression was increased with ADSC differentiation. Using synthetic miRNAs to
      mimic or inhibit the action of miR-33a revealed that miR-33a hinders the
      differentiation of ADSCs towards urothelial cells. Furthermore, luciferase
      reporter assay confirmed that beta-catenin and transforming growth factor-beta
      receptor (TGFR) are targets of miR-33a. Inhibition of miR-33a expression
      increased beta-catenin and TGFR expression and improved the efficiency of ADSCs
      towards differentiation into the urothelium phenotype. The present novel finding
      suggests that miR-33 may be an important target in tissue engineering and
      regenerative medicine for urothelium repair.

PMID- 29207163
TI  - Preclinical analysis of MTOR complex 1/2 inhibition in diffuse intrinsic pontine
      glioma.
AB  - Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood brain tumor.
      The mechanistic target of rapamycin (MTOR), a key oncogene, functions as two
      distinct signaling complexes, MTORC1 and MTORC2. We set out to determine the
      preclinical efficacy and mechanism of action of MTOR inhibitors in DIPG. We
      evaluated the MTORC1 inhibitor everolimus and the MTORC1/2 inhibitor AZD2014 in
      three patient-derived DIPG cell lines using cell culture models. We created dose
      response curves for both compounds. We measured phenotypic effects on cell self
      renewal, apoptosis, cell cycle, differentiation, senescence, and autophagy. We
      assessed the effects of each compound on the AKT pathway. Finally, we measured
      the efficacy of AZD2014 in combination with radiation therapy (RT) and a panel of
      FDA-approved chemotherapy drugs. While everolimus showed minimal antitumor
      efficacy, AZD2014 revealed IC50 levels of 410-552 nM and IC90 levels of 1.30-8.86
      uM in the three cell lines. AZD2014 demonstrated increased inhibition of cell
      self-renewal compared to everolimus. AZD2014 decreased expression of phospho-AKT,
      while no such effect was noted with everolimus. Direct AKT inhibition showed
      similar efficacy to AZD2014, and induction of constitutive AKT activity rescued
      DIPG cells from the effects of AZD2014. AZD2014 exhibited synergistic
      relationships with both RT and various chemotherapy agents across classes,
      including the multikinase inhibitor ponatinib. MTORC1/2 inhibition shows
      antitumor activity in cell culture models of DIPG due to the effect of MTORC2
      inhibition on AKT. This strategy should be further assessed for potential
      incorporation into combinatorial approaches to the treatment of DIPG.

PMID- 29207164
TI  - Silencing TGIF suppresses migration, invasion and metastasis of MDA-MB-231 human
      breast cancer cells.
AB  - This study explored the potential role of TG-interacting factor (TGIF) in
      migration, invasion and metastasis of the human breast cancer cell line MDA-MB
      231. Western blot assay, immunohistochemistry and qRT-PCR assays were applied to
      detect the expression of protein and mRNA. Wound healing assay, Transwell
      invasion assay and tail vein metastatic assay were performed to assess the
      migration, invasion and metastasis of stable TGIF-silenced MDA-MB-231 cell line
      in vitro and in vivo. The significantly higher frequency of TGIF high-expression
      was observed in metastatic breast cancer (62.9%) compared to that in non
      metastatic breast cancer (25.8%). Silencing TGIF suppressed migration and
      invasion of MDA-MB-231 cells in vitro and tumor metastasis in nude mouse models.
      The expression of Snail1, matrix metalloproteinase 2 (MMP2) and beta-catenin was
      markedly decreased in the stable TGIF-silenced MDA-MB-231 cells compared with the
      control cells. Our results suggest that silencing TGIF suppressed the migration,
      invasion and metastasis of the human breast cancer cell line MDA-MB-231 using in
      vitro and in vivo experiments.

PMID- 29207165
TI  - Combination treatment of FTY720 and cisplatin exhibits enhanced antitumour
      effects on cisplatin-resistant non-small lung cancer cells.
AB  - A major common medical treatment for lung carcinoma is cisplatin (DDP)-based
      therapy. However, the development or existence of chemoresistance frequently
      blocks its effectiveness. Currently, autophagy is recognised as a potential
      anticancer strategy, although there is controversy over its role in the
      development of cancer. In lung carcinoma, no studies of autophagy induced by
      FTY720, a sphingosine 1-phosphate analog and a novel immunosuppressant drug, have
      been published, while apoptosis has been shown to be induced by FTY720 in several
      cancer cell lines. We evaluated the effects of FTY720 on autophagy in A549 cells
      and studied the related mechanisms of cell autophagy and apoptosis in non-small
      cell lung carcinoma, including both DDP-resistant and -sensitive cells. The
      results revealed that FTY720 inhibited the growth and induced apoptosis in the
      A549/DDP cells in a time- and dose-dependent manner and the combination of FTY720
      and DDP further enhanced apoptosis in these cells as determined by CCK-8 assay,
      western blotting and flow cytometry. Compared with the sensitive cell line A549,
      DDP-resistant A549/DDP cells showed a substantial increase in baseline autophagy
      as determined by increased LC puncta, and expression of LC3-I, LC3-II and Atg7
      expression. DDP-induced apoptotic cell death was enhanced by the blockade of
      either siRNA-mediated knockdown of Atg7 genetic expression or a pharmacological
      inhibitor (3-MA). Moreover, the combination of FTY720 and DDP showed enhanced
      antitumour activity in vivo in lung cancer-bearing mice. Immunohistochemistry
      showed that the mice with lung carcinoma treated with FTY720 and DDP showed
      decreased expression of Atg7 and Ki67. Compared with monotherapy in vivo and in
      vitro, FTY720 in combination with DDP inhibited A549 cell growth more
      effectively. and these findings also show the influence of FTY720 in the
      induction of autophagy. Overall, the results indicated that FTY720 in combination
      with a DDP-based regime could enhance the effectiveness of lung carcinoma
      treatment.

PMID- 29207166
TI  - Pentosan polysulfate ameliorates apoptosis and inflammation by suppressing
      activation of the p38 MAPK pathway in high glucose-treated HK-2 cells.
AB  - The apoptosis of tubular epithelial cells in diabetic nephropathy (DN) is
      commonly observed in human renal biopsies. Inflammation plays a key role in DN,
      and pentosan polysulfate (PPS) has been shown to largely attenuate the
      inflammation of nephropathy in aging diabetic mice. p38 mitogen-activated protein
      kinase (p38 MAPK) plays a crucial role in tissue inflammation and cell apoptosis,
      and it is activated by hyperglycemia. In the present study, high glucose (HG)
      treated human renal proximal tubular epithelial cells (HK-2) were used to examine
      the protective effects of PPS against HG-stimulated apoptosis and inflammation.
      The results of the study revealed that PPS markedly suppressed the HG-induced
      reduction in cell viability. Incubation of HK-2 cells with HG activated the p38
      MAPK pathway and, subsequently, as confirmed by western blot analysis and flow
      cytometry, increased cell apoptosis, which was blocked by PPS. In addition, PPS
      treatment significantly inhibited HG-stimulated p38 MAPK and nuclear factor
      kappaB activation, and reduced the production of pro-inflammatory cytokines, such
      as tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6. In conclusion,
      PPS ameliorates p38 MAPK-mediated renal cell apoptosis and inflammation. The anti
      apoptotic actions and anti-inflammatory effects of PPS prompt further
      investigation of this compound as a promising therapeutic agent against DN.

PMID- 29207167
TI  - Prazosin protects myocardial cells against anoxia-reoxygenation injury via the
      extracellular signal-regulated kinase signaling pathway.
AB  - Ischemic heart disease (including coronary arterial atherosclerosis, or vascular
      cavity stenosis or occlusion) remains the leading cause of disease-associated
      mortality worldwide. Prazosin, a receptor blocker of postsynaptic adrenaline, is
      essential in expanding peripheral arteries, which decreases peripheral vascular
      resistance, and regulates anti-hypertensive action. However, the mechanisms
      underlying the effects of prazosin have not been fully elucidated. The aim of the
      present study was to investigate the protective effects of prazosin on myocardial
      cells against anoxia-reoxygenation injury in a mouse model. The regulatory
      effects of prazosin on blood lipid levels and blood pressure were investigated in
      experimental mice. Furthermore, inflammation responses and oxidative stress in
      myocardial cells were analyzed in mice treated with prazosin. Apoptotic
      myocardial cells were investigated in experimental mice treated with prazosin. In
      addition, apoptotic gene expression levels were evaluated in myocardial cells.
      Extracellular signal-regulated kinase (ERK) expression and phosphorylation was
      investigated in myocardial cells in mice with anoxia-reoxygenation injury
      following prazosin treatment. The activity and expression levels of nuclear
      factor of activated T cells (NF-AT), activator protein 1 (AP-1) and necrosis
      factor (NF)-kappaB were observed in myocardial cells. Furthermore, histological
      analyses were performed to investigate the benefits of prazosin treatment on
      anoxia-reoxygenation injury. The results of the present study identified that
      prazosin decreased the expression levels of inflammatory factors, interleukin
      (IL)-6, tumor necrosis factor (TNF)-alpha, IL-10 and IL-1 in the serum of mice
      exhibiting hypoxia/reoxygenation injury. Oxidative stress was observed to be
      improved and the apoptosis rate was decreased in myocardial cells in anoxia
      reoxygenation injury model mice treated with prazosin. ERK expression and
      phosphorylation was upregulated, and expression levels of NF-AT, AP-1 and NF
      kappaB were downregulated in the myocardial cells of mice treated with prazosin.
      Blood lipid levels and blood pressure of the anoxia-reoxygenation injury model
      mice were markedly improved following treatment with prazosin. Histological
      analysis indicated that the area, circumference fragmentation and segmentation of
      myocardial cells were significantly improved following prazosin treatment. Thus,
      these results indicate that prazosin treatment decreases inflammation responses,
      oxidative stress, and apoptosis of myocardial cells via regulation of the ERK
      signaling pathway. The findings indicate that prazosin may present as a potential
      therapeutic agent for the treatment of hypoxia/reoxygenation injury.

PMID- 29207168
TI  - Targeted next-generation sequencing reveals two novel mutations of NBAS in a
      patient with infantile liver failure syndrome-2.
AB  - Mutations in neuroblastoma amplified sequence (NBAS) cause infantile liver
      failure syndrome-2 (ILFS2). NBAS is a protein involved in Golgi-to-endoplasmic
      reticulum retrograde transport. Exon capture in combination with high-throughput
      sequencing was used to detect NBAS mutations. Via targeted sequencing, two
      causative mutations were identified from 358 selected genes associated with
      growth and development diseases; one was a missense mutation, c.3596G>A
      (p.C1199Y), detected in the coding region of NBAS (NM_015909.3), and the other a
      splice site mutation, c.209+1G>A. Both of these were heterozygous. The SEC39
      structure of the wild-type NBAS protein was compared with a model of the mutated
      protein. The overall structure of the SEC39 after mutation did not change;
      however, steric hindrance did increase. In conclusion, two novel NBAS mutations
      were identified in a 4-year-old Chinese girl with ILFS2.

PMID- 29207169
TI  - Daam1 activates RhoA to regulate Wnt5a-induced glioblastoma cell invasion.
AB  - The signaling pathway of dishevelled-associated activator of morphogenesis 1
      (Daam1) triggered by Wnt5a drives cell movement and migration during breast
      cancer metastasis. However, Wnt5a signaling in glioblastoma progression remains
      poorly defined. Wnt5a expression and activations of RhoA, Cdc42, and Rac1 were
      detected in human glioblastoma tissues by using ELISA assays and small G-protein
      activation assays, respectively. The cell invasion rate and Daam1 activation of
      glioblastoma U251 and T98MG cells were determined by cell invasion assays and
      pull-down assays, respectively. According to our experiments, Wnt5a expression
      and RhoA activation were upregulated in invasive glioblastoma tissues, with a
      significant positive correlation between them. Wnt5a activated Daam1 and RhoA,
      and subsequently promoted the invasion of glioblastoma U251 and T98MG cells. This
      process was abolished by secreted frizzled-related protein 2 (sFRP2), an
      antagonist that directly binds to Wnt5a. Specific small interfering RNA (siRNA)
      targeting Daam1 markedly inhibited Wnt5a-induced RhoA activation, stress fiber
      formation and glioblastoma cell invasion. CCG-1423, a RhoA inhibitor, decreased
      Wnt5a-induced stress fiber formation and glioblastoma cell invasion. Finally,
      siRNA targeting Daam1 or CCG-1423 treatment did not alter the cell proliferation
      of glioblastoma U251 and T98MG cells. We thus concluded that Wnt5a promoted
      glioblastoma cell invasion via Daam1/RhoA signaling pathway.

PMID- 29207170
TI  - BMI-1 suppression increases the radiosensitivity of oesophageal carcinoma via the
      PI3K/Akt signaling pathway.
AB  - B-cell-specific Moloney murine leukaemia virus integration site-1 (BMI-1)
      contributes to the growth of tumour cells post-irradiation (IR). The aim of the
      present study was to characterize the effects of BMI-1 on cell viability,
      radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer
      (ESCC). Western blotting and immunohistochemistry were employed to evaluate the
      protein expression of BMI-1 in ESCC cells and specimens, respectively.
      Additionally, the protein expression levels of BMI-1, H2AK119ub and gammaH2AX in
      ESCC cells were detected following different doses of IR and at different times
      after IR. The protein expression levels of MDC1 and 53BP1 were also measured.
      Flow cytometry and MTT assays were used to determine cell cycle progression,
      apoptosis and cell viability. The phosphatidylinositol 3-kinase inhibitor
      LY294002 and the agonist IGF-1 were employed to suppress or induce the
      phosphorylation of Akt to determine whether BMI-1 induces radioresistance in ESCC
      cells via activation of the PI3K/Akt pathway. The expression of BMI-1 was higher
      in ESCC tissues and cells compared with that in normal oesophageal tissues and
      cells. In addition, BMI-1 was positively related to tumour size and lymph node
      metastases and negatively to the overall survival of ESCC patients. IR induced
      the expression of BMI-1, H2AK119ub and gammaH2AX in a dose- and time-dependent
      manner. BMI-1 knockdown lowered the expression of gammaH2AX, MDC1 and 53BP1,
      suppressed cell viability and increased radiosensitivity. G2/M phase arrest was
      eliminated; this was followed by an increased proportion of cells entering the
      G0/G1 phase after IR and BMI-1 knockdown via the upregulation of P16 and
      downregulation of cyclin D2 and cyclin-dependent kinase-4. Moreover, BMI-1
      knockdown increased cell apoptosis, downregulated MCL-1 and p-Akt and upregulated
      Bax. Additionally, the inhibitory effect of the downregulation of p-Akt by
      LY294002 on tumour cell viability was identical to that of BMI-1 knockdown, while
      the kinase agonist IGF-1 reversed the effects of BMI-1 knockdown on cell
      viability and radiosensitivity. Taken together, BMI-1 knockdown induces
      radiosensitivity in ESCC and significantly inhibits cell viability, which may
      contribute to an increased proportion of cells in the G0/G1 phase and cell
      apoptosis via suppression of the PI3K/Akt signalling pathway.

PMID- 29207171
TI  - Ginsenoside Rh2 inhibits human A172 glioma cell proliferation and induces cell
      cycle arrest status via modulating Akt signaling pathway.
AB  - Ginsenoside Rh2 (G-Rh2), the main bioactive component in American ginseng, is
      known to exert a wide variety of biological activities. Accumulating evidence
      suggests that G-Rh2 inhibits cell proliferation and induces apoptosis of tumor
      cells. However, the possible mechanism through which G-Rh2 exerts its action on
      malignant glioma cells have not been completely elucidated. The findings of the
      present study demonstrated that G-Rh2 decreased the viability of glioma cells in
      a dose- and time-dependent manner, and induced cell cycle arrest. G-Rh2-induced
      cell cycle arrest was accompanied by the downregulation of cyclin-dependent
      kinase 4 and Cyclin E. In addition, G-Rh2 markedly reduced the expression of
      total- RAC-alpha serine/threonine-protein kinase (Akt) and the levels of
      phosphorylated-Akt. These findings provide mechanistic details of how G-Rh2 acts
      on glioma cells and suggest that G-Rh2 may function as a potential anti-cancer
      drug for glioma treatment.

PMID- 29207173
TI  - microRNA-196b promotes cell migration and invasion by targeting FOXP2 in
      hepatocellular carcinoma.
AB  - Accumulating evidence indicates that microRNAs (miRNAs) play important roles in
      tumorigenesis and metastasis. Recent research has shown that miR-196b is
      implicated in metastasis by regulating the migration and invasion of cancer
      cells. However, the clinical significance of miR-196b and its role as well as the
      underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unknown.
      Here, we detected miR-196b expression in HCC and matched non-tumor tissues with
      qRT-PCR. We found that miR-196b displayed higher expression in HCC patient
      tissues and cells. Clinical analysis revealed that high miR-196 expression was
      correlated with venous infiltration, advanced TNM stage and poor prognosis.
      Functionally, we demonstrated that miR-196b promoted the migration and invasion
      of HCC cells in vitro. Moreover, miR-196b knockdown restrained pulmonary
      metastasis in vivo. Mechanistically, we confirmed that miR-196b could directly
      bind to 3'UTR of forkhead box P2 (FOXP2) mRNA and repress its expression. miR
      196b and FOXP2 showed a negative correlation in HCC tissues. More importantly,
      upregulation of FOXP2 antagonized miR-196b-mediated migration and invasion in
      Hep3B cells. Furthermore, FOXP2 knockdown partially reversed the anti-metastatic
      function of the miR-196b inhibitor on HCCLM3 cells. Taken together, we
      demonstrated that miR-196b may function as a prognostic biomarker and suppressed
      FOXP2 expression, subsequently leading to the metastasis of HCC. Our findings
      highlight a novel mechanism of miR-196b in the progression of HCC and identify
      miR-196b/FOXP2 axis as a promising target for HCC.

PMID- 29207172
TI  - Ran-binding protein M is associated with human spermatogenesis and oogenesis.
AB  - The aim of the present study was to explore the underlying mechanism and
      diagnostic potential of Ran-binding protein M (RanBPM) in human spermatogenesis
      and oogenesis. RanBPM expression in human testis and ovaries was analysed using
      polymerase chain reaction (PCR) and western blotting, and immunofluorescence was
      performed on testis and ovary tissue sections during different developmental
      stages of spermatogenesis and oogenesis using RanBPM antibodies. Interactions
      with a variety of functional proteins were also investigated. RanBPM mRNA and
      protein expression levels were determined by PCR and western blotting in the
      tissue sections. Results revealed that the mRNA expression levels were highest in
      the testis followed by the ovary. The RanBPM protein was predominantly localized
      in the nucleus of germ cells, and the expression levels were highest in pachytene
      spermatocytes and cells surrounding spermatids in testis tissue. In ovary cells,
      RanBPM was localized in the nucleus and cytoplasm. In conclusion, the results
      suggested that RanBPM may have multiple roles in the regulation of germ cell
      proliferation during human spermatogenesis and oogenesis. This research may
      provide a novel insight into the underlying molecular mechanism of RanBPM and may
      have implications for the clinical diagnosis and treatment of human infertility.

PMID- 29207174
TI  - Calcium channels are involved in EphB/ephrinB reverse signaling-induced apoptosis
      in a rat chronic ocular hypertension model.
AB  - Erythropoietin-producing hepatocyte receptor B (EphB)/ephrinB reverse signaling
      has been revealed to be activated in chronic ocular hypertension (COH) by
      increasing the apoptosis of retinal ganglion cells (RGCs). However, the exact
      mechanism is not well understood. The present study investigated the involvement
      of Ca2+ channels in the apoptosis of RGCs induced by EphB/ephrinB reverse
      signaling in a rat CHO model, which was established by cauterizing 3 out of the 4
      episcleral veins. The expression levels of four voltage-gated Ca2+ channel
      subunits (Cav3.1-3.3 and Cav1.2) were detected using immunofluorescence and
      western blot analysis. TUNEL staining was performed to assess RGC apoptosis
      following an injection with the T type Ca2+ channel blocker. Ca2+ channels,
      mainly the T type, were upregulated in COH rat retinas when compared with the
      sham group (P<0.01). Additionally, the Cav3.2 subunit of T type calcium channels
      was predominantly expressed in Muller cells and RGCs, such as ephrinB2.
      Furthermore, an intravitreal injection of the Ca2+ channel blocker Mibefradil (3
      uM) reduced EphB2-fragment crystallizable region-induced RGC apoptosis in normal
      rats. Thus, the results suggest that Ca2+ channels in a COH model may be a
      pathway involved in ephrinB/EphB signaling-induced RGC apoptosis.

PMID- 29207175
TI  - Hypermethylation of the SPARC promoter and its prognostic value for prostate
      cancer.
AB  - Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular
      glycoprotein and plays a key role in the development of many tissues and organ
      types. However, the role of SPARC in prostate cancer (PCa) is still
      controversial. The aim of the present study was to investigate the abnormalities
      in the expression of SPARC and its promoter hypermethylation in prostate cancers
      and in correlated clinicopathological profiles. We examined the hypermethylation
      of the SPARC promoter as a potential mechanism for suppressing SPARC in PCa. The
      clinicopathological correlation between SPARC and its promoter expression and the
      prognostic significance of the aberrantly expressed genes were evaluated to
      identify novel biomarkers of PCa. SPARC expression was decreased in PCa cell
      lines, which correlated with hypermethylation of the SPARC promoter. Treatment
      with the demethylating agent 5-Aza-Cdr restored SPARC expression. Seventy percent
      (145 of 207) of the primary tumors exhibited SPARC hypermethylation, while only
      2.6% was found in normal prostate mucosa (n=38). In PCa cases, SPARC
      hypermethylation was correlated with a poorer prognosis (P=0.005; relative risk
      2.659, 95% CI, 1.433-4.562). Our findings revealed potential diagnostic markers
      of PCa based on specific hypermethylated CpG sites and also provided new insights
      of SPARC as a novel biomarker and/or treatment modality for prostate cancer.

PMID- 29207176
TI  - P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of
      diffuse gliomas.
AB  - Diffuse gliomas are the most common type of primary brain and central nervous
      system (CNS) tumors. Protein disulfide isomerases (PDIs) such as P4HB and PDIA3
      act as molecular chaperones for reconstructing misfolded proteins, and are
      involved in endoplasmic reticulum stress and the unfolded protein response. The
      present study focused on the role of P4HB and PDIA3 in diffuse gliomas. Analysis
      of GEO and HPA data revealed that the expression levels of P4HB and PDIA3 were
      upregulated in glioma datasets. their increased expression was then validated in
      99 glioma specimens compared with 11 non-tumor tissues. High expression of P4HB
      and PDIA3 was significantly correlated with high Ki-67 and a high frequency of
      the TP53 mutation. Kaplan-Meier survival curve and Cox regression analyses showed
      that glioma patients with high P4HB and PDIA3 expression had a poor survival
      outcome, P4HB and PDIA3 could be independent prognostic biomarkers for diffuse
      gliomas. In vitro, knockdown of PDIA3 suppressed cell proliferation, induced cell
      apoptosis, and decreased the migration of glioma cells. Furthermore,
      downregulation of P4HB and PDIA3 may contribute to improve the survival of
      patients who receive chemotherapy and radiotherapy. The data suggest that high
      expression of P4HB and PDIA3 plays an important role in glioma progression, and
      could predict the survival outcome and therapeutic response of glioma patients.
      Therefore, protein disulfide isomerases may be explored as prognostic biomarkers
      and therapeutic targets for diffuse gliomas.

PMID- 29207177
TI  - Regulation of steroid hormones in the placenta and serum of women with
      preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific hypertensive syndrome that results in
      substantial maternal and fetal morbidity and mortality. The exact cause of PE has
      not been completely elucidate, although abnormal formation of the placenta has
      been considered. The placenta connects the developing fetus to the uterine wall,
      producing a large quantity of steroid hormones to maintain pregnancy. Although
      steroid hormones, particularly progesterone (P4) and estrogen (E2), in the serum
      of women with PE have been studied, steroidogenesis in the placenta has not well
      been established. The present study compared the concentrations of steroid
      hormones, including pregnenolone (PG), P4, dehydroepiandrosterone (DHEA),
      testosterone (T) and E2, in the serum and placenta of women with PE. PG, P4, DHEA
      and E2 concentrations tended to be decreased in PE serum and placentas, and the
      results were statistically significant for P4 and E2 in the serum. Quantification
      of genes associated with steroidogenesis in the placenta was performed, and the
      expression of the P4- and E2-synthesizing enzymes testosterone 17-beta
      dehydrogenase 3 and 3 beta-hydroxysteroid dehydrogenase/delta5 4-isomerase type 1
      was reduced. Notably, aromatase, an enzyme required for the production of E2, was
      upregulated in the PE placenta, suggesting that steroidogenic enzymes may be
      dynamically regulated and may affect the symptoms of PE. In conclusion, the
      results of the present study suggested that the levels of steroid hormones,
      including P4 and E2, in the serum and placenta of women with PE are
      downregulated, which may be mediated by the regulation of steroidogenic enzyme
      expression in the PE placenta.

PMID- 29207178
TI  - miR-328-3p enhances the radiosensitivity of osteosarcoma and regulates apoptosis
      and cell viability via H2AX.
AB  - Osteosarcoma is a kind of high-risk sarcoma of the skeleton typically observed in
      people under 25 years old. Currently, radiotherapy is widely applied in cancer
      treatment. However, osteosarcoma is radioresistant and accordingly new, more
      effective radiosensitizers are needed. miRNAs have been reported to play an
      important role in osteosarcoma radiosensitivity. We examined the modulating
      effect of miR-328-3p in vivo and in vitro. miR-328-3p was downregulated in HOS-2R
      cells. The overexpression of miR-328-3p enhanced the radiosensitivity of
      osteosarcoma cells. miR-328-3p inhibited proliferation and promoted apoptosis in
      osteosarcoma cells under radiation conditions. In cells overexpressing miR-328
      3p, H2AX expression was downregulated. We found that miR-328-3p targets H2AX and
      inhibits its expression. It was concluded, that miR-328-3p enhances the
      radiosensitization of osteosarcoma following X-ray irradiation, and determined
      that it directly targets H2AX to regulate radiosensitization.

PMID- 29207179
TI  - Arctigenin induces the apoptosis of primary effusion lymphoma cells under
      conditions of glucose deprivation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary
      effusion lymphoma (PEL) and Kaposi's sarcoma. PEL is a type of non-Hodgkin's B
      cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or
      AIDS patients. However, since PEL is resistant to chemotherapeutic regimens, new
      effective treatment strategies are required. Arctigenin, a natural lignan
      compound found in the plant Arctium lappa, has been widely investigated as a
      potential anticancer agent in the clinical setting. In the present study, we
      examined the cytotoxic effects of arctigenin by cell viability assay and found
      that arctigenin markedly inhibited the proliferation of PEL cells compared with
      KSHV-uninfected B-lymphoma cells under conditions of glucose deprivation.
      Arctigenin decreased cellular ATP levels, disrupted mitochondrial membrane
      potential and triggered caspase-9-mediated apoptosis in the glucose-deprived PEL
      cells. In addition, western blot analysis using phospho-specific antibodies were
      used to evaluate activity changes in the signaling pathways of interest. As a
      result, arctigenin suppressed the activation of the extracellular signal
      regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK)
      signaling pathways by inhibiting ERK and p38 MAPK phosphorylation in the glucose
      deprived PEL cells. We confirmed that an inhibitor of ERK (U0126) or p38 MAPK
      (SB202190 and SB203580) suppressed the proliferation of the BC3 PEL cells
      compared with the KSHV-negative DG75 cells. Moreover, RT-PCR and luciferase
      reporter assay revealed that arctigenin and p38 MAPK inhibition by SB202190 or
      SB203580 downregulated the transcriptional expression of unfolded protein
      response (UPR)-related molecules, including GRP78 and ATF6alpha under conditions
      of glucose deprivation. Finally, we confirmed that arctigenin did not affect KSHV
      replication in PEL cells, suggesting that arctigenin treatment for PEL does not
      contribute to the risk of de novo KSHV production. These data thus indicate that
      arctigenin may serve as a lead compound for the development of novel and
      effective drugs for the treatment of PEL.

PMID- 29207180
TI  - MicroRNA-411 inhibits malignant biological behaviours of colorectal cancer cells
      by directly targeting PIK3R3.
AB  - Colorectal cancer (CRC) is the third most common cancer and the fourth leading
      cause of cancer-related mortality worldwide. Aberrant expression of miRNAs play
      important roles in the development and progression of various types of cancers by
      modulating oncogenic and tumour-suppressor pathways. Therefore, exploring the
      functions of microRNAs (miRNAs) that specifically contribute to CRC
      tumourigenesis and tumour development would greatly aid in obtaining more
      information on CRC and provide new targets for its diagnosis and treatment. miRNA
      411 (miR-411) was previously observed to be aberrantly expressed in multiple
      human cancers. However, the expression pattern, function and underlying molecular
      mechanism of miR-411 in CRC remain unclear. Therefore, the present study was
      performed to detect miR-411 expression, investigate the biological roles of miR
      411 and identify its mechanism of action in CRC cells. Here, miR-411 expression
      was significantly downregulated in human CRC tissues and cell lines, and low
      levels of miR-411 were correlated with lymph node metastasis, distant metastasis
      and TNM stage. Resumed expression of miR-411 suppressed cell proliferation and
      invasion but promoted apoptosis in CRC. Additionally, phosphoinositide-3-kinase
      regulatory subunit 3 (PIK3R3) was identified as a direct target of miR-411 in
      CRC. PIK3R3 was upregulated in the CRC tissues and inversely correlated with miR
      411 expression. Downregulation of PIK3R3 had tumour-suppressive effects similar
      to those of miR-411 overexpression in CRC. Moreover, upregulation of PIK3R3 could
      rescue the tumour-suppressing effects of miR-411 overexpression in CRC cells.
      More importantly, miR-411 specifically suppressed the activation of the AKT/mTOR
      signalling pathway in CRC. Therefore, miR-411 functions as a tumour-suppressive
      miRNA by directly targeting PIK3R3 and indirectly regulating AKT/mTOR signalling
      pathway. miR-411 may serve as a new therapeutic target for patients with CRC.

PMID- 29207181
TI  - Function of miR-212 as a tumor suppressor in thyroid cancer by targeting SIRT1.
AB  - miR-212 as a tumor suppressor has been reported to be downregulated in multiple
      cancer cells lines and tumor tissues. However, its role in thyroid cancer has nor
      been investigated. Therefore, the present study aimed to investigate the role of
      miR-212 in human thyroid cancer and the underlying mechanisms. In the present
      study, we demonstrated that miR-212 expression was significantly decreased in
      thyroid cancer specimens and cell lines compared with adjacent normal tissues and
      normal thyroid cell lines. In addition, we demonstrated that miR-212
      downrwegulation in thyroid cancer tissues was negatively associated with lymph
      node metastasis and advanced clinical stage. Functionally, ectopic expression of
      miR-212 by transfection with miR-212 mimic significantly inhibited proliferation,
      colony formation, migration and invasion in TPC-1 cells. In addition, Sirtuin 1
      (SIRT1) was identified as a direct target of miR-212 and its expression was
      inversely correlated with miR-212 expression in thyroid cancer tissues.
      Overexpression of SIRT1 could effectively rescue miR-212 mimic-induced
      suppression of cell proliferation, migration and invasion in TPC-1 cells. In
      vivo, miR-212 overexpression significantly inhibited tumor growth in a nude mice
      model. In light of these findings, miR-212 may function as a tumor suppressor in
      thyroid cancer by targeting SIRT1.

PMID- 29207183
TI  - Src homology phosphotyrosyl phosphatase 2 mediates cisplatin-related drug
      resistance by inhibiting apoptosis and activating the Ras/PI3K/Akt1/survivin
      pathway in lung cancer cells.
AB  - Cisplatin resistance is a major cause of chemotherapeutic failure in lung cancer
      patients. Unraveling the molecular mechanisms underlying cisplatin (CDDP)
      resistance is important in lung cancer therapeutics. To explore the role of Src
      homology phosphotyrosyl phosphatase 2 (SHP2) in the development of cisplatin
      resistance in lung cancer and the underlying mechanism, we established stable
      SHP2-overexpressing H446-SHP2-OE cells and SHP2-knockdown H446/CDDP-SHP2-shRNA
      cells derived from H446 and H446/CDDP (cisplatin-resistant) parental lung cancer
      cells. The cell viability and apoptosis of these cells exposed to CDDP were
      observed to determine the influence of SHP2 on drug resistance. In addition, the
      expression of SHP2, Ras, Akt1 and survivin was assessed by western blot analysis
      after the lung cancer cells were challenged by cisplatin or silenced by Ras
      siRNA. As a result, the 50% inhibitory concentration (IC50) of the H446-SHP2-OE
      cells exposed to CDDP increased from 1.01 to 1.218 ug/ml vs. the H446-control
      vector cells. The percentage of apoptotic cells was smaller in the H446-SHP2-OE
      cells vs. the H446-control vector cells after cisplatin challenge. In addition,
      the expression of Ras, pAkt1, Akt1 and survivin in the H446/CDDP cells was
      significantly increased vs. the H446 cells. Furthermore, the IC50 of the
      H446/CDDP-SHP2-shRNA cells exposed to CDDP decreased from 11.92 to 4.382 ug/ml
      vs. the H446/CDDP-mock cells. There were significantly more apoptotic cells among
      the H446/CDDP-SHP2-shRNA cells vs. the H446/CDDP-mock cells exposed to cisplatin.
      A smaller percentage of the H446/CDDP-SHP2-shRNA cells vs. the H446/CDDP-mock
      cells was observed. In addition, the expression of pAkt1 and survivin in the
      H446, H446/CDDP and H446/CDDP-mock cells was increased upon exposure to cisplatin
      however, a corresponding change was not observed in the H446/CDDP-SHP2-shRNA
      cells. Upon Ras RNA silencing with cisplatin, the Ras expression was
      significantly decreased in the H446, H446-SHP2-OE and H446/CDDP cells. However,
      upon Ras RNA interference, the SHP2 expression was not significantly changed, but
      the expression of Akt1, pAkt1 and survivin was significantly increased in the
      H446-SHP2-OE and H446/CDDP cells. In conclusion, SHP2 is a new cisplatin
      resistance-related phosphatase in lung cancer, which inhibits apoptosis by
      activating the Ras/PI3K/Akt1/survivin signaling pathway.

PMID- 29207182
TI  - Antitumor activity of the synthetic retinoid ST1926 on primary effusion lymphoma
      in vitro and in vivo models.
AB  - Primary effusion lymphoma (PEL) is a rare B-cell neoplasm, associated with Kaposi
      sarcoma-associated herpes virus/human herpes virus-8 (KSHV/HHV-8), arising as
      malignant effusions in body cavities. PEL cells do not harbor conventional
      genetic cancer mutations; however, their oncogenesis is mainly attributed to HHV
      8 latent genes. Treatment strategies are inefficient resulting in poor prognosis
      of PEL patients, stressing the need for new effective therapy. ST1926 is a
      synthetic retinoid with favorable antitumor properties and no cross-resistance
      with the natural retinoid, all-trans retinoic acid. ST1926 has shown potent
      apoptotic activities on a variety of solid tumors and hematologic malignancies in
      in vitro and in vivo models. In the present study we elucidated the antitumor
      activities and underlying molecular mechanism of ST1926 using in vitro, ex vivo,
      and in vivo PEL preclinical models. ST1926, at sub-micromolar concentrations,
      displayed potent antiproliferative effects on PEL cell lines and malignant
      ascites. Furthermore, ST1926 treatment of PEL cells and ascites resulted in their
      accumulation in the sub-G1 region, S phase cell cycle arrest, early DNA damage,
      PARP cleavage and p53 activation including the upregulation of its target genes
      p21 and Bax. However, ST1926 did not significantly modulate HHV-8 latent viral
      transcripts. Importantly, ST1926 delayed formation of ascites and enhanced
      survival of PEL mice. These results highlight the therapeutic potential of ST1926
      in combination with drugs that target HHV-8 in PEL patients.

PMID- 29207184
TI  - Cullin 7 is a predictor of poor prognosis in breast cancer patients and is
      involved in the proliferation and invasion of breast cancer cells by regulating
      the cell cycle and microtubule stability.
AB  - Cullin 7 is the 'scaffold' of the cullin-RING-based E3 ligases which catalyze the
      final step of the ubiquitination cascade in eukaryotic organisms. Although one
      study has reported the involvement of cullin 7 in the invasion and migration of
      breast cancer cells without further exploration of its mechanisms, the expression
      of cullin 7 in breast cancer tissues and its clinical significance have not been
      reported. The present study evaluated cullin 7 protein expression in malignant
      and benign breast tissues using immunochemistry, and further analyzed the
      association of positive cullin 7 expression in breast cancer tissues with
      clinicopathological characteristics of breast cancer patients. Cullin 7
      expression was further silenced in breast cancer cells by siRNA and its functions
      and mechanisms in cell proliferation and invasion were investigated. The results
      showed that high cullin 7 expression was significantly correlated with
      pathological stage (P=0.013) and lymph node metastasis (P=0.022) of breast
      cancer. Patients with high cullin 7 expression had a shorter overall survival
      rate than those with low cullin 7 expression (P=0.037). Silencing of cullin 7
      expression significantly inhibited the proliferation (P<0.05) and invasion
      (P<0.05), increased S1 phase (P<0.05), but decreased G2 phase (P<0.05) in MDA-MB
      231 and BT549 cells. In addition, silencing of cullin 7 expression decreased
      cyclin A, but increased p21 protein expression. Moreover, silencing of cullin 7
      expression altered the cell shape, caused disorder in microtubules, and increased
      the microtubule regeneration in MDA-MB-231 and BT549 cells. In conclusion, cullin
      7 is overexpressed in breast cancer tissues which is associated with the
      development and prognosis of breast cancer. Cullin 7 is involved in the
      proliferation and invasion of breast cancer cells by regulating the cell cycle
      and microtubule stability.

PMID- 29207185
TI  - Novel multi-kinase inhibitor, T03 inhibits Taxol-resistant breast cancer.
AB  - Activation of kinase-associated signaling pathways is one of the leading causes
      of various malignant phenotypes in breast tumors. Strategies of drug discovery
      and development have investigated approaches to target the inhibition of protein
      kinase signaling. In the current study, the anti-tumor activities of a novel
      multi-kinase inhibitor, T03 were evaluated in breast cancer. T03 inhibited Taxol
      resistant breast cancer cell proliferation and induced cell cycle arrest and
      apoptosis in vitro and in vivo. The current results demonstrated that T03
      downregulated c-Raf, platelet-derived growth factor receptor-beta and other
      kinases, thus inhibited Raf/mitogen-activated protein kinase kinase/extracellular
      signal-regulated kinase and Akt/mechanistic target of rapamycin survival pathways
      in MCF-7 and MCF-7/Taxol xenograft tumors. At a dose of 100 mg/kg, T03 inhibited
      tumor growth by 62.90 and 59.98% in tumor weight in MX-1 and MX-1/T xenograft
      models, respectively and by 62.60 and 60.22% in MCF-7 and MCF-7/T tumors,
      respectively. These data indicate that the novel multi-kinase inhibitor, T03, may
      present as a potential compound to develop novel treatments against breast cancer
      and Taxol-resistant breast tumors.

PMID- 29207186
TI  - Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma
      cells by activating the PI3K/AKT pathway.
AB  - Our previous study demonstrated that neuroglobin (Ngb) functions as an
      independent predictive indicator of the prognosis of patients with glioma and
      promotes cancer cell growth by suppressing apoptosis. However, the understanding
      of the mechanisms underlying the survival-enhancing function of Ngb in glioma is
      limited. In the present study, KEGG PathwayFinder by gene correlation analysis
      was performed on the R2: Genomics Analysis and Visualization Platform, which
      revealed a high association between Ngb and the phosphatidylinositol 3-kinase
      (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus
      database. Furthermore, western blotting experiments were performed in U251 and
      U87 glioma cells, and Ngb knockdown using short hairpin RNA reduced the protein
      levels of phosphorylated (p)-AKT, p-mammalian target of rapamycin (mTOR) and
      antiapoptotic factor Bcl-2, and increased the expression of the proapoptotic
      protein Bcl-2-associated X, in U251 cells. In addition, Ngb overexpression
      promoted the activation of the PI3K/AKT pathway in U87 cells. MK2206, a PI3K/AKT
      signaling inhibitor, reduced the expression of p-AKT and increased the levels of
      apoptosis-associated proteins, including cleaved poly(ADP-ribose) polymerase 1
      and cleaved caspase-3/7/8, in Ngb-overexpressing U87 cells. Furthermore, MK2206
      treatment reduced the proliferation and induced the apoptosis of Ngb
      overexpressing U87 cells, as indicated by the results of MTT, colony formation
      and flow cytometry assays. In addition, insulin-like growth factor-1, a PI3K/AKT
      signaling activator, reversed Ngb knockdown-induced growth arrest and apoptosis
      in U251 cells. In conclusion, the results of the present study indicate that Ngb
      may facilitate a malignant phenotype of glioma cells by activating the PI3K/AKT
      pathway.

PMID- 29207187
TI  - Macrophage migration inhibitory factor rescues mesenchymal stem cells from
      doxorubicin-induced senescence though the PI3K-Akt signaling pathway.
AB  - Doxorubicin (DOXO), an anthracycline antibiotic, is a commonly used anticancer
      drug. Despite its widespread usage, the therapeutic effects of DOXO are limited
      by its cardiotoxicity. Mesenchymal stem cell (MSC)-based therapies have had
      positive outcomes in the treatment of DOXO-induced cardiac damage; however, DOXO
      exerts toxic effects on MSCs, decreasing the effectiveness of MSC therapy.
      Macrophage migration inhibitory factor (MIF) promotes MSC survival and
      rejuvenation, and thus is a promising candidate to protect MSCs against DOXO
      induced injury. The present study revealed that DOXO induced the senescence of
      MSCs, resulting in decreased proliferation, viability and paracrine effects.
      However, pretreatment with MIF improved the proliferation rate, viability,
      paracrine function, telomere length and telomerase activity of MSCs. Furthermore,
      the results indicated that the molecular mechanism underlying the anti-senescent
      function of MIF involved the phosphatidylinositol 3-kinase (PI3K)-RAC-alpha
      serine/threonine-protein kinase (Akt) signaling pathway, which MIF activated. In
      agreement with this finding, silencing Akt was identified to abolish the anti
      senescent effect of MIF. In addition, MIF decreased oxidative stress in MSCs, as
      revealed by the decreased production of reactive oxygen species and
      malondialdehyde, and the increased activity of superoxide dismutase. These
      results indicate that MIF can rescue MSCs from a state of DOXO-induced senescence
      by inhibiting oxidative stress and activating the PI3K-Akt signaling pathway.
      Thus, treatment with MIF may have an important therapeutic application for the
      rejuvenation of MSCs in patients with cancer being treated with DOXO.

PMID- 29207188
TI  - Glycyrrhizic acid induces human MDA-MB-231 breast cancer cell death and autophagy
      via the ROS-mitochondrial pathway.
AB  - Glycyrrhizic acid (GA), the main component of licorice root extracts, has been
      shown to suppress cell proliferation and induce apoptosis in various types of
      cancers. However, the molecular mechanism of its anticancer activity remains
      poorly understood and warrants further investigation. MDA-MB-231 cells were
      treated with various concentrations of GA and the cytotoxic effects of GA were
      determined using the CCK-8 assay. Apoptosis and cell cycle status were detected
      by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial
      membrane potential (?Psim) were assessed using DCFDA, MitoSOX and JC-1 staining.
      Western blot analysis was used to quantify the expression of autophagy-related
      proteins. In the present study, induction of autophagic cell death was observed
      in GA-treated MDA-MB-231 cells. Downregulation of p62- and beclin 1-associated
      proteins occurred after GA treatment, and, the conversion of LC3 and increased
      ROS without significant changes in caspase-associated proteins and intracellular
      responses were detected. Furthermore, loss of mitochondria and its membrane
      potential in cells demonstrated that mitochondria were involved in the GA
      regulated MDA-MB-231 cell death. The addition of a pan-caspase inhibitor (z-VAD
      fmk) did not suppress the GA-induced apoptotic effect, and GA-induced apoptosis
      was not accompanied by processing of procaspase-8, -9 and -3. However, GA
      triggered the translocation of the apoptosis-inducing factor (AIF) from the
      mitochondria into the nucleus. In contrast, GA-induced LC3 conversion was
      significantly inhibited by 3 methlyadenine (3MA), an inhibitor of PI3K-regulated
      autophagy. Therefore, these results suggest that enhancement of both AIF- and LC3
      dependent GA-derived ROS generation plays an important role in the inhibition of
      the growth of MDA-MB-231 human breast cancer cells.

PMID- 29207189
TI  - Overexpression of COUP-TFII suppresses proliferation and metastasis of human
      gastric cancer cells.
AB  - The abnormal expression of the chicken ovalbumin upstream promoter transcription
      factor 2 (COUP-TFII) is associated with numerous forms of cancer, including
      gastric, prostate, colon and lung cancer. However, previous studies investigating
      the association between COUP-TFII expression and the occurrence, recurrence,
      invasion and metastasis of gastric cancer are limited in number. In the present
      study, it was revealed that the expression of COUP-TFII is significantly reduced
      in gastric carcinoma tissues compared with normal gastric mucosa cells (GES-1).
      In addition, the expression of COUP-TFII was also reduced in gastric cancer cell
      lines compared with GES-1 cells. Furthermore, it was revealed that ectopic
      expression of COUP-TFII was able to suppress the proliferation, migration and
      invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In
      addition, it was demonstrated that COUP-TFII knockdown was able to promote the
      proliferation, migration and invasion of GES-1 cells in vitro. Furthermore,
      database analysis suggested that COUP-TFII expression in patients with gastric
      cancer is correlated with clinical stage classification and increased expression
      levels of COUP-TFII improved overall survival rates in patients with gastric
      cancer. The results of the present study suggest that COUP-TFII functions as a
      significant regulatory suppressor of gastric cancer growth and metastasis, and
      suggests that COUP-TFII may serve as a novel diagnostic and prognostic biomarker
      for gastric cancer metastasis.

PMID- 29207190
TI  - Anticancer potential of novel curcumin analogs towards castrate-resistant
      prostate cancer.
AB  - Prostate cancer is initially sensitive to hormone therapy; however, over time the
      majority of patients progress to a hormone-insensitive form classified as
      castration-resistant prostate cancer (CRPC). CRPC is highly metastatic and
      patients have a poor prognosis. Thus, new drugs for the treatment of this disease
      are required. In this study, we therefore examined the cytotoxic effects and
      anticancer mechanism(s) of action of second generation curcumin analogs towards
      CRPC cells. For this purpose, PC3 and DU145 cells were treated with a series of
      curcumin analogs at 0-10 uM for 72 h and cytotoxicity was determined by the
      sulforhodamine B (SRB) assay. Two compounds, 1-isopropyl-3,5-bis(pyridin-3
      ylmethylene)-4-piperidone (RL118) and 1-methyl-3,5-[(6-methoxynaphthalen-2
      yl)methylene]-4-piperidone (RL121), were found to have the most potent cytotoxic
      effect with EC50 values of 0.50 and 0.58 uM in the PC3 cells and EC50 values of
      0.76 and 0.69 uM in the DU145 cells, respectively. Thus, further experiments were
      performed focusing on these two compounds. Flow cytometry was performed to
      determine their effects on the cell cycle and apoptosis. Both analogs increased
      the number of cells in the G2/M phase of the cell cycle and induced apoptosis.
      Specifically, in the PC3 cells, RL121 increased the number of cells in the G2/M
      phase by 86% compared to the control, while RL118 increased the number of cells
      in the G2/M phase by 42% compared to the control after 24 h. Moreover, both RL118
      and RL121 induced the apoptosis of both cell lines. In the DU145 cells, a 38-fold
      increase in the number of apoptotic cells was elicited by RL118 and a 78-fold
      increase by RL121 compared to the control. Furthermore, the effects of both
      analogs on the expression of key proteins involved in cell proliferation were
      also determined by western blot analysis. The results revealed that both analogs
      inhibited the expression of nuclear factor (NF)-kappaB (p65/RelA), eukaryotic
      translation initiation factor 4E-binding protein 1 (4E-BP1), p-4E-BP1, mammalian
      target of rapamycin (mTOR), p-mTOR, AKT and p-AKT. Thus, the findings of this
      study provide evidence that RL118 and RL121 have potent anticancer activity
      against CPRC cells, and both analogs warrant further investigation in vivo.

PMID- 29207191
TI  - Novel evidence that pituitary sex hormones regulate migration, adhesion, and
      proliferation of embryonic stem cells and teratocarcinoma cells.
AB  - The pituitary sex hormones (SexHs): follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), and prolactin (PRL) regulate several functions crucial
      for reproduction, including oogenesis, spermatogenesis, and lactation. An
      important source of prolactin-like hormones, known as lactogens, is the placenta,
      and lactogens bind to the PRL receptor (PRLR) with high affinity and thereby
      mimic the actions of PRL. Recently, it has been demonstrated that pituitary SexHs
      were involved in metastatic lung cancer, certain sarcomas, and leukemia. In the
      present study we aimed to investigate whether FSH, LH, and PRL were able to
      stimulate stem cells involved in early development. To address this issue we
      employed a murine embryonic stem cell line (ES-D3) as well as two teratocarcinoma
      cell lines, P19 (murine) and NTera2 (human). We determined that all these cells
      expressed SexH receptors at the mRNA and protein levels and that stimulation of
      these receptors induced phosphorylation of p42/44 MAPK, p38 MAPK, and AKT.
      Moreover, ES-D3, P19, and NTera2 cells responded with increased migration and
      adhesion to physiological concentrations of pituitary SexHs. In view of these
      findings we proposed that maternal-derived pituitary SexHs regulate the biology
      of stem cells involved in early development.

PMID- 29207192
TI  - Resveratrol attenuates hydrogen peroxide-induced apoptosis, reactive oxygen
      species generation, and PSGL-1 and VWF activation in human umbilical vein
      endothelial cells, potentially via MAPK signalling pathways.
AB  - Reactive oxygen species (ROS) are implicated in the pathogenesis of thrombosis.
      Studies have reported that resveratrol exhibits antioxidative activities,
      however, the effect and underlying mechanisms of resveratrol on venous thrombosis
      remain largely unknown. To investigate the effect of resveratrol on venous
      thrombosis and the underlying mechanisms, the present study investigated the
      effects of resveratrol on cell viability, apoptosis, ROS generation and the
      expression of thrombosis-associated markers in human umbilical vein endothelial
      cells (HUVECs). HUVECs were pretreated with resveratrol for 2 h and incubated
      with hydrogen peroxide (H2O2) for 24 h prior to the evaluation of cell viability,
      ROS generation, apoptosis and thrombosis-associated marker expression by
      performing MTT assays, 2',7'-dichlorofluorescin diacetate reagent, flow
      cytometry, and reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) and western blot analysis, respectively. Subsequently, to validate whether
      resve-ratrol functions via mitogen-activated protein kinase (MAPK) pathways, the
      expression of thrombosis-associated markers was detected by western blot analysis
      and RT-qPCR following treatment of cells with resveratrol and the MAPK pathway
      activators anisomycin and curcumin. The results demonstrated that cell viability
      was markedly reduced by H2O2, and resveratrol treatment reversed the reductions
      in cell viability in a dose-dependent manner. In addition, the levels of cell
      apoptosis and ROS generation were significantly increased by H2O2 alone, and
      resveratrol also reduced these effects in a dose-dependent manner. Furthermore,
      the mRNA and protein expression of caspase-3, P-selectin glycoprotein ligand-1
      and von Willebrand factor was upregulated by H2O2 treatment in HUVECs. However,
      resveratrol decreased the protein expression these proteins in a dose-dependent
      manner. Resveratrol also significantly inhibited the induction of phosphorylated
      (p)-p38, P-c-Jun N-terminal kinase and P-extracellular signal-regulated kinase by
      H2O2, and these effects were attenuated by the MAPK pathway activators anisomycin
      and curcumin. In conclusion, these results indicate that resveratrol protected
      HUVECs against oxidative stress and apoptosis. Furthermore, to the best of our
      knowledge, the present study is the first to demonstrate that resveratrol
      attenuates the expression of thrombosis-associated markers induced by H2O2, which
      may occur through the suppression of the MAPK signalling pathways, indicating a
      potential novel therapeutic approach to prevent venous thrombosis.

PMID- 29207193
TI  - All-trans retinoic acid reduces endothelin-1 expression and increases endothelial
      nitric oxide synthase phosphorylation in rabbits with atherosclerosis.
AB  - All-trans retinoic acid (ATRA) is a natural derivative of vitamin A that
      ameliorates atherosclerosis (AS) by regulating inflammatory factors. However,
      studies concerning the role of retinoic acid in artery endothelial function are
      rare. Therefore, the present study investigated its role in regulating the
      production of endothelin-1 (ET-1) and nitric oxide (NO) in rabbits with AS. The
      rabbits were randomly divided into 3 groups: The control group was administered
      an ordinary diet, while the high fat group and the ATRA drug intervention group
      were administered a high fat diet. After 12 weeks, the blood lipid levels of
      rabbits, the morphological structure of the arterial wall, the arterial intimal
      permeability, the activity of blood endothelial nitric oxide synthase (eNOS) and
      the level of plasma NO were investigated. Western blot analysis was used to
      detect the levels of ET-1, eNOS and eNOS phosphorylation at Ser-1177 (p-eNOS),
      and a radioimmunoassay was performed to detect the level of ET-1 in the plasma.
      It was identified that plaque formation was alleviated in the ATRA group compared
      with the high fat group, as revealed by hematoxylin and eosin and oil red O
      staining, and a similar trend was reflected in the immunofluorescence results for
      endothelial permeability. Western blotting demonstrated significantly decreased
      ET-1 expression levels in the arterial tissue of rabbits in the ATRA group
      compared with the high fat group, together with increased p-eNOS level (P<0.05),
      however, no difference was observed in the expression of eNOS (P>0.05). The
      trends observed for ET-1 and the activity of eNOS in plasma were similar to those
      for arterial tissue. Therefore, the present study demonstrated that ATRA may
      regulate the grade of AS by the reduction of ET-1 secretion and increased NO
      formation via increased phosphorylation of eNOS. ATRA provides a potential novel
      method for the treatment of atherosclerosis.

PMID- 29207194
TI  - Quercetin synergistically reactivates human immunodeficiency virus type 1 latency
      by activating nuclear factor-kappaB.
AB  - Highly active antiretroviral therapy (HAART) is very effective in suppressing
      human immunodeficiency virus type 1 (HIV-1) replication. However, the treatment
      is required to be administered for the remainder of an individual's lifetime due
      to latent HIV-1 reservoirs. The 'shock-and-kill' strategy, which involves using
      agents to reactivate latent HIV-1 and subsequently killing latently infected
      cells in the presence of HAART, was recently proposed. Unfortunately, no agents
      have currently demonstrated an ability to reactivate latent HIV-1 in vivo in the
      absence of toxicity. Therefore, the identification of novel latency activators is
      required. In order to identify a potential novel agent, the present study
      investigated the effect of quercetin on latent HIV-1 reactivation using an
      established model of HIV-1 latency. As a marker for reactivation of HIV-1 in C11
      Jurkat cells, the expression of green fluorescent protein, controlled by HIV-1
      long terminal repeat, was observed by fluorescence microscopy. The results of the
      present study demonstrated that quercetin effectively reactivated latent HIV-1
      gene expression alone, and led to synergistic reactivation when combined with
      prostratin or valproic acid. In addition, the present study provides evidence
      that quercetin may reactivate HIV-1 expression by inducing nuclear factor-kappaB
      nuclear translocation, and that the toxicity of quercetin is lower when compared
      with various additional activators of HIV-1. Combined, the results of the present
      study indicate that quercetin may be an effective agent to disrupt HIV-1 latency
      and may be useful in future eradication strategies.

PMID- 29207195
TI  - A novel correlation between ATP5A1 gene expression and progression of human clear
      cell renal cell carcinoma identified by co-expression analysis.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common solid lesion within
      kidneys, and its prognostic is influenced by the progression covering a complex
      network of gene interactions. In our study, a weighted gene co-expression network
      was constructed to identify gene modules associated with the progression of ccRCC
      (n=35). In the significant module (R2 = -0.53), a total of 13 network hub genes
      were identified, and 2 of them were hub nodes in the protein-protein interaction
      network as well. In validation, ATP5A1 showed a higher correlation with the
      disease progression than any other hub gene in the hub module (P=0.001219). In
      the test set (n=202), ATP5A1 was also highly expressed in normal kidney than
      ccRCC tissues of each grade (P<0.001). Functional and pathway enrichment analysis
      demonstrated that ATP5A1 is overrepresented in pathway of oxidative
      phosphorylation, which associated with tumorigenesis and tumor progression. Gene
      set enrichment analysis (GSEA) also demonstrated that the gene set of 'oxidative
      phosphorylation' and metabolic pathways were enriched in ccRCC samples with
      ATP5A1 highly expressed (P<0.05). In conclusion, based on the co-expression
      analysis, ATP5A1 was validated to be associated with progression of ccRCC,
      probably by regulating tumor-related phosphorylation.

PMID- 29207196
TI  - High-resolution metabolomics determines the mode of onset of type 2 diabetes in a
      3-year prospective cohort study.
AB  - Type 2 diabetes mellitus (DM) is a progressive disease and the rate of
      progression from non-diabetes to DM varies considerably between individuals,
      ranging from a few months to many years. It is important to understand the
      mechanisms underlying the progression of diabetes. In the present study, a high
      resolution metabolomics (HRM) analysis was performed to detect potential
      biomarkers and pathways regulating the mode of onset by comparing subjects who
      developed and did not develop type 2 DM at the second year in a 3-year
      prospective cohort study. Metabolic profiles correlated with progression to DM
      were examined. The subjects (n=98) were classified into four groups: Control (did
      not develop DM for 3 years), DM (diagnosed with DM at the start of the study), DM
      onset at the third year and DM onset at the second year. The focus was on the
      comparison of serum samples of the DM groups with onset at the second and third
      year from the first year, where these two groups had not developed DM, yet.
      Analyses involved sample examination using liquid chromatography-mass
      spectrometry-based HRM and multivariate statistical analysis of the data.
      Metabolic differences were identified across all analyses with the affected
      pathways involved in metabolism associated with steroid biosynthesis and bile
      acid biosynthesis. In the first year, higher levels of cholesterol {mass-to
      charge ratio (m/z) 369.35, (M+H-H2O)+}, 25-hydroxycholesterol [m/z 403.36,
      (M+H)+], 3alpha,7alpha-dihydroxy-5beta-cholestane [m/z 443.33, (M+K)+], 4alpha
      methylzymosterol-4-carboxylate [m/z 425.34, (M+H-H2O)+], and lower levels of
      24,25-dihydrolanosterol [m/z 429.40, (M+H)+] were evident in the group with DM
      onset at the second year compared with those in the group with DM onset at the
      third year. These results, with a focus on the cholesterol biosynthesis pathway,
      point to important aspects in the development of DM and may aid in the
      development of more effective means of treatment and prevention.

PMID- 29207197
TI  - Prohibitin-2 negatively regulates AKT2 expression to promote prostate cancer cell
      migration.
AB  - Prostate cancer (PCa) is a leading cause of cancer-associated mortality in men;
      however, the factors that contribute to disease development have yet to be fully
      elucidated. Previous studies have suggested that prohibitin-2 (PHB2), which is a
      multifunctional protein that contributes to various cellular processes, is
      positively correlated with malignant progression of PCa; however, the molecular
      mechanisms underlying the effects of PHB2 on the enhancement of cell migration
      have not been identified. The present study induced overexpression and knockdown
      of PHB2 in PCa cell lines (PC3 and DU145) with the aim of examining the effects
      of PHB2 on PCa cell migration via wound healing assays. The results indicated
      that PHB2 overexpression promoted migration of both cell lines. AKT
      serine/threonine kinase 2 (AKT2), which interacts with PHB2, has been reported to
      participate in cell migration; therefore, the present study examined the effects
      PHB2 overexpression and knockdown on AKT2 in PCa cells. The present study
      demonstrated that overexpression of PHB2 reduced the expression of AKT2, whereas
      PHB2 knockdown increased AKT2 expression in both PCa cell lines. In addition,
      knockdown of PHB2 enhanced the protein stability of AKT2. Furthermore, AKT2
      overexpression resulted in a significant decrease in migration, whereas AKT2
      knockdown promoted migration of PC3 and DU145 PCa cells. The combined
      overexpression of PHB2 and AKT2 inhibited migration of both cell lines, thus
      suggesting that AKT2 overexpression abolished PHB2-induced migration.
      Mechanistically, the present study suggested that PHB2 may promote PCa cell
      migration by inhibiting the expression of AKT2. These results provide information
      regarding the role of PHB2 in PCa migration and malignancy.

PMID- 29207198
TI  - Mechanism of triptolide in treating ankylosing spondylitis through the anti
      ossification effect of the BMP/Smad signaling pathway.
AB  - The present study aimed to examine the mechanism of triptolide in the treatment
      of ankylosing spondylitis (AS) through the anti-ossification effect of bone
      morphogenetic protein (BMP)/small mothers against decapentaplegic (Smad) pathway.
      Male rats were randomly divided into five groups: Normal rat group; model group;
      triptolide low dose group (10 mg/kg); triptolide middle dose group (20 mg/kg);
      triptolide high dose group (40 mg/kg). The spinal joint capsules of each group of
      rats were collected to perform primary cell culture to determine the levels of
      cell proliferation. Western blot and reverse transcription-polymerase chain
      reaction analyses, and ELISA were used to detect the mRNA and protein expression
      levels of core-binding factor alpha1 (Cbfal), BMP receptor type II (BMPRII),
      Smad1, Smad4, Smad5 and Smad6, the protein expression of phosphorylation
      indicators, including phosphorylated (p)Smad1 and pSmad5, the mRNA expression of
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 in rat
      plasma, and the mRNA expression of BMP/Smads in fibroblasts induced by
      recombinant human (rh)BMP-2. The effects on AS in the rats were also examined.
      The results revealed that, following intervention with triptolide, inflammation
      was suppressed, and the mRNA expression levels of TNF-alpha, IL-1beta and IL-6
      were reduced. The expression levels of Cbfal, BMPRII, Smad1, Smad4 and Smad5 were
      also reduced, whereas the expression of Smad6 was increased. Following induction
      by rhBMP-2, the effects of triptolide weakened, with the most marked effects
      observed at the highest concentration, suggesting that triptolide functions
      through the BMP/Smad signaling pathway. Taken together, the results suggested
      that triptolide may be used to treat AS, the mechanism of which may be through
      the BMP/Smad pathway.

PMID- 29207199
TI  - Genes and pathways associated with the occurrence of malignancy in benign
      lymphoepithelial lesions.
AB  - There is increasing evidence concerning the occurrence of malignant lymphoma
      among people suffering from Mikulicz disease, also termed benign lymphoepithelial
      lesion (BLEL) and immunoglobulin G4-associated disease. However, the underlying
      molecular mechanism of the malignant transformation remains unclear. The present
      study aimed to investigate the gene expression profile between BLEL and malignant
      lymphoepithelial lesion (MLEL) conditions using tissue microarray analysis, to
      identify genes and pathways which may be associated with the risk of malignant
      transformation. Comparing gene expression profiles between BLEL tissues (n=13)
      and MLEL (n=14), a total of 1,002 differentially expressed genes (DEGs) were
      identified including 364 downregulated and 638 upregulated DEGs in BLEL. The
      downregulated DEGs in BLEL were frequently associated with immune-based
      functions, immune cell differentiation, proliferation and survival, and metabolic
      functions, whereas the upregulated DEGs were primarily associated with organ,
      gland and tissue developmental processes. The B cell receptor signaling pathway,
      the transcription factor p65 signaling pathway, low affinity immunoglobulin gamma
      Fc region receptor II-mediated phagocytosis, the high affinity immunoglobulin
      epsilon receptor subunit gamma signaling pathway and Epstein-Barr virus
      infection, and pathways in cancer, were the pathways associated with the
      downregulated DEGs. The upregulated DEGs were associated with three pathways,
      including glutathione metabolism, salivary secretion and mineral absorption
      pathways. These results suggested that the identified signaling pathways and
      their associated genes may be crucial for understanding the molecular mechanisms
      underlying malignant transformation from BLEL, and they may be considered to be
      markers for predicting malignancy among the BLEL group.

PMID- 29207200
TI  - Effect of TW37 on the growth of H1975 EGFR-TKI-resistant lung cancer cells and
      its underlying mechanisms.
AB  - Previous studies have suggested that the B-cell lymphoma 2 (Bcl-2) inhibitor,
      TW37, may induce apoptosis of the non-small cell lung cancer cell line,
      H1975/epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI),
      which exhibits secondary resistance to EGFR-TKI. However, the effects of TW37 on
      H1975/EGFR-TKI cells remain unclear. The aim of the present study was to
      investigate the effects of TW37 on the growth of H1975/EGFR-TKI cells and explore
      the underlying mechanisms. An in vitro study was performed, whereby H1975/EGFR
      TKI cells were treated with serially increasing concentrations of TW37. MTT, flow
      cytometry, migration and transwell invasion assays were preformed to investigate
      the proliferation, apoptosis, migration and invasion of H1975/EGFR-TKI cells,
      respectively. In addition, reverse transcription-polymerase chain reaction and
      western blot analyses were performed to detect the mRNA and protein expression
      levels of apoptosis-associated factors, respectively. An enzyme-linked
      immunosorbent assay was performed to detect phosphatidylinositol [3,4,5] tris
      phosphate (PIP3) expression. The results suggested that the mRNA and protein
      expression levels of Bcl-2 were significantly decreased in TW37-treated cells
      when compared with the untreated control group. Following treatment with TW37,
      the proliferation, migration and invasion ability of H1975/EGFR-TKI cells
      decreased in a dose-dependent manner, while the percentage of apoptotic cells
      increased. In addition, the results demonstrated that TW37 reduced the expression
      of PIP3 and the phosphorylation of AKT serine/threonine kinase 1 (AKT) in
      H1975/EGFR-TKI cells in a dose-dependent manner. In conclusion, TW37 inhibited
      H1975/EGFR-TKI cell growth and induced cell apoptosis potentially via suppression
      of AKT signaling pathway activation.

PMID- 29207202
TI  - Synthesis, Structure, and Acidity Constants of Ligated alpha-Boryl Acetic Acids.
AB  - Basic hydrolyses of various ligated alpha-boryl acetic acid esters provided the
      first ligated derivatives of the unknown compound boroacetic acid (BH2 CH2 CO2
      H). Four monoacids (L-BH2 CH2 CO2 H) and one diacid (L-BH(CH2 CO2 H)2 ) were
      prepared with N-heterocyclic carbene, amine, and pyridine ligands (L). The stable
      acids were characterized by X-ray crystallography and acidity constant (pKa )
      measurements. They rank among the least acidic of all known carboxylic acids. In
      turn, their conjugate bases are among the strongest of all carboxylates.

PMID- 29207201
TI  - Hypoxia modulates the stem cell population and induces EMT in the MCF-10A breast
      epithelial cell line.
AB  - A common feature among pre-malignant lesions is the induction of hypoxia through
      increased cell propagation and reduced access to blood flow. Hypoxia in breast
      cancer has been associated with poor patient prognosis, resistance to
      chemotherapy and increased metastasis. Although hypoxia has been correlated with
      factors associated with the latter stages of cancer progression, it is not well
      documented how hypoxia influences cells in the earliest stages of transformation.
      Using the immortalized MCF-10A breast epithelial cell line, we used hypoxic
      culture conditions to mimic reduced O2 levels found within early pre-malignant
      lesions and assessed various cellular parameters. In this non-transformed mammary
      cell line, O2 deprivation led to some changes not immediately associated with
      cancer progression, such as decreased proliferation, cell cycle arrest and
      increased apoptosis. In contrast, hypoxia did induce other changes more
      consistent with an increased metastatic potential. A rise in the CD44+CD24-/low
      labeled cell sub-population along with increased colony forming capability
      indicated an expanded stem cell population. Hypoxia also induced cellular and
      molecular changes consistent with an epithelial-to-mesenchymal transition (EMT).
      Furthermore, these cells now exhibited increased migratory and invasive
      abilities. These results underscore the contribution of the hypoxic tumour
      microenvironment in cancer progression and dissemination.

PMID- 29207203
TI  - A Rotaxane Scaffold Bearing Multiple Redox Centers: Synthesis, Surface
      Modification and Electrochemical Properties.
AB  - A rotaxane scaffold incorporating two dithiolane anchoring units for the
      modification of gold surfaces has been functionalized with multiple copies of a
      redox unit, namely ferrocene. Surface modification has been first assessed at the
      single molecule level by atomic force microscopy (AFM) and scanning tunneling
      microscopy (STM) imaging, while tip enhanced Raman spectroscopy (TERS) provided
      the local vibrational signature of the ferrocenyl subunits of the rotaxanes
      grafted onto the gold surface. Finally, oxidation of the redox moieties within a
      rotaxane scaffold grafted onto gold microelectrodes has been investigated by
      ultrafast cyclic voltammetry. Intramolecular electron hopping is indeed extremely
      fast in this system. Moreover, the kinetics of charge injection depends on the
      molecular coverage due to the influence of intermolecular contacts on molecular
      motions.

PMID- 29207204
TI  - Cocoa production: Monocultures are not the solution to climate adaptation
      Response to Abdulai et al. 2017.

PMID- 29207205
TI  - Rebuttal from David Simpson and Jurgen Claassen.

PMID- 29207206
TI  - Spontaneous Covalent Self-Assembly of the Azoarcus Ribozyme from Five Fragments.
AB  - Spontaneous covalent assembly of short RNA fragments has been proposed as a
      plausible prebiotically relevant pathway to a self-reproducing system. We
      previously showed that the Azoarcus group I intron could self-assemble from four
      RNA fragments. Here, we extended this fragmentation to five RNAs that averaged
      <40 nucleotides in length. We optimized this reaction and showed that a
      dehydration-rehydration sequence was the most effective means to date to shift
      the self-assembly equilibrium from reactants to products.

PMID- 29207207
TI  - Synthesis of Functionalized Nitriles by Microwave-Promoted Fragmentations of
      Cyclic Iminyl Radicals.
AB  - The synthesis of functionalized nitriles via microwave-promoted radical
      fragmentations of cyclic O-phenyl oxime ethers is reported. A variety of radical
      traps can be employed, permitting the generation of diverse adducts via C-O, C-C,
      C-N, or C-X bond formation. Other salient features include a simple and practical
      protocol, very short reaction times, and the avoidance of metal catalysts and
      toxic cyanide reagents. The utility of this method is demonstrated by the ring
      distortion of a steroid-derived substrate.

PMID- 29207208
TI  - CrossTalk opposing view: dynamic cerebral autoregulation should be quantified
      using induced (rather than spontaneous) blood pressure fluctuations.

PMID- 29207210
TI  - Rebuttal from Y. C. Tzeng and R. B. Panerai.

PMID- 29207212
TI  - Hydrophilicity and Microsolvation of an Organic Molecule Resolved on the Sub
      molecular Level by Scanning Tunneling Microscopy.
AB  - Low-temperature scanning tunneling microscopy was used to follow the formation of
      a solvation shell around an adsorbed functionalized azo dye from the attachment
      of the first water molecule to a fully solvated molecule. Specific functional
      groups bind initially one water molecule each, which act as anchor points for
      additional water molecules. Further water attachment occurs in areas close to
      these functional groups even when the functional groups themselves are already
      saturated. In contrast, water molecules surround the hydrophobic parts of the
      molecule only when the two-dimensional solvation shell closes around them. This
      study thus traces hydrophilic and hydrophobic properties of an organic molecule
      down to a sub-molecular length scale.

PMID- 29207211
TI  - Preparation and Electrochemical Properties of NiCo2 O4 Nanospinels Supported on
      Graphene Derivatives as Earth-Abundant Oxygen Bifunctional Catalysts.
AB  - This work reports on the facile synthesis and characterisation of a non-precious
      metal bifunctional catalyst for oxygen reduction and evolution reactions (ORR and
      OER). A few-layer reduced graphene oxide-supported NiCo2 O4 catalyst is prepared
      using a rapid and easy two-step method of synthesis. It consists of the
      solvothermal poyl(vinylpyrrolidone)-assisted assembly of metal complexes onto few
      layer graphene followed by a calcination step aiming at converting metal
      complexes into the spinel phase. Using this synthesis approach, the most active
      material demonstrates an outstanding activity towards the OER and ORR, making it
      one of the best bifunctional catalysts of these reactions ever reported. This
      composite catalyst exhibits improved bifunctional behaviour with a low
      reversibility criterion of 746 mV. The ORR process follows a four-electron
      pathway and the hydroxyl selectivity is higher than those with pure reduced
      graphene oxide or NiCo2 O4 materials, showing the synergistic effect between the
      two phases. Moreover, the high activity of this composite catalyst is confirmed
      by comparing its performance with those obtained on other cobaltite catalysts
      prepared using a different synthesis method, or those obtained using a different
      graphene-based support.

PMID- 29207213
TI  - CrossTalk proposal: dynamic cerebral autoregulation should be quantified using
      spontaneous blood pressure fluctuations.

PMID- 29207214
TI  - Feed thickener for infants up to six months of age with gastro-oesophageal
      reflux.
AB  - BACKGROUND: Gastro-oesophageal reflux (GOR) is common in infants, and feed
      thickeners are often used to manage it in infants as they are simple to use and
      perceived to be harmless. However, conflicting evidence exists to support the use
      of feed thickeners. OBJECTIVES: To evaluate the use of feed thickeners in infants
      up to six months of age with GOR in terms of reduction in a) signs and symptoms
      of GOR, b) reflux episodes on pH probe monitoring or intraluminal impedance or a
      combination of both, or c) histological evidence of oesophagitis. SEARCH METHODS:
      We used the standard search strategy of the Cochrane Neonatal Review Group to
      search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue
      2), MEDLINE via PubMed (1966 to 22 November 2016), Embase (1980 to 22 November
      2016), and CINAHL (1982 to 22 November 2016). We also searched clinical trials
      databases, conference proceedings, and the reference lists of retrieved articles
      for randomised controlled trials. SELECTION CRITERIA: We included randomised
      controlled trials if they examined the effects of feed thickeners as compared to
      unthickened feeds (no treatment or placebo) in treating GOR in term infants up to
      six months of age or six months of corrected gestational age for those born
      preterm. DATA COLLECTION AND ANALYSIS: Two review authors independently
      identified eligible studies from the literature search. Two review authors
      independently performed data extraction and quality assessments of the eligible
      studies. Differences in opinion were resolved by discussion with a third review
      author, and consensus was reached among all three review authors. We used the
      GRADE approach to assess the quality of the evidence. MAIN RESULTS: Eight trials
      recruiting a total of 637 infants met the inclusion criteria for the systematic
      review. The infants included in the review were mainly formula-fed term infants.
      The trials were of variable methodological quality. Formula-fed term infants with
      GOR on feed thickeners had nearly two fewer episodes of regurgitation per day
      (mean difference -1.97 episodes per day, 95% confidence interval (CI) -2.32 to 
      1.61; 6 studies, 442 infants, moderate-certainty evidence) and were 2.5 times
      more likely to be asymptomatic from regurgitation at the end of the intervention
      period (risk ratio 2.50, 95% CI 1.38 to 4.51; number needed to treat for an
      additional beneficial outcome 5, 95% CI 4 to 13; 2 studies, 186 infants, low
      certainty evidence) when compared to infants with GOR on unthickened feeds. No
      studies reported failure to thrive as an outcome. We found low-certainty evidence
      based on 2 studies recruiting 116 infants that use of feed thickeners improved
      the oesophageal pH probe parameters of reflux index (i.e. percentage of time pH <
      4), number of reflux episodes lasting longer than 5 minutes, and duration of
      longest reflux episode. No major side effects were reported with the use of feed
      thickeners. Information was insufficient to conclude which type of feed thickener
      is superior. AUTHORS' CONCLUSIONS: Gastro-oesophageal reflux is a physiological
      self resolving phenomenon in infants that does not necessarily require any
      treatment. However, we found moderate-certainty evidence that feed thickeners
      should be considered if regurgitation symptoms persist in term bottle-fed
      infants. The reduction of two episodes of regurgitation per day is likely to be
      of clinical significance to caregivers. Due to the limited information available,
      we were unable to assess the use of feed thickeners in infants who are
      breastfeeding or preterm nor could we conclude which type of feed thickener is
      superior.

PMID- 29207215
TI  - Unique preening behavior may use light and heat to facilitate ectoparasite
      removal in green herons (Butorides virescens).

PMID- 29207216
TI  - The roles of cellular and molecular components of a hematoma at early stage of
      bone healing.
AB  - Bone healing is a complex repair process that commences with the formation of a
      blood clot at the injured bone, termed hematoma. It has evidenced that a lack of
      a stable hematoma causes delayed bone healing or non-union. The hematoma at the
      injured bone constitutes the early healing microenvironment. It appears to
      dictate healing pathways that ends in a regenerative bone. However, the hematoma
      is often clinically removed from the damaged site. Conversely, blood-derived
      products have been used in bone tissue engineering for treating critical sized
      defects, including fibrin gels and platelet-rich plasma. A second generation of
      platelet concentrate that is based on leukocyte and fibrin content has also been
      developed and introduced in market. Conflicting effect of these products in bone
      repair are reported. We propose that the bone healing response becomes
      dysregulated if the blood response and subsequent formation and properties of a
      hematoma are altered. This review focuses on the central structural, cellular,
      and molecular components of a fracture hematoma, with a major emphasis on their
      roles in regulating bone healing mechanism, and their interactions with
      mesenchymal stem cells. New angles towards a better understanding of these
      factors and relevant mechanisms involved at the beginning of bone healing may
      help to clarify limited or adverse effects of blood-derived products on bone
      repair. We emphasize that the recreation of an early hematoma niche with critical
      compositions might emerge as a viable therapeutic strategy for enhanced skeletal
      tissue engineering.

PMID- 29207217
TI  - [Clinical competence in Nephrology: proposal of an evaluation pathway and
      definition of professional levels].
AB  - The need to assess clinical competencies in a medical environment is an
      intriguing issue due to progressive involvement of young physicians in clinical
      practice, as well as for connections tied to evaluation systems to define
      postgraduate training and career progression. To reach this goal, system must be
      based upon contributions that are aimed to achieve a clear and homogeneous
      evaluation pathway and strictly related to the continuing medical education
      institution (credits). All these presuppositions are instrumental for the
      proposal of a sheet which could allow a data retrieval useful to depict a career
      progression by means of: identification of reproducible parameters along with
      clear standards; advices for indicators; objective judgments that could drive to
      a score meaningful for reaching higher steps in the performance evaluation. This
      work had been carried out at Local Health Authority 1 of Cuneo (ASLCN1) from 2014
      to 2017 in order to provide a widely usable evaluation framework for all the
      medical workers. Aim of this work is thus to show up an original methodology, as
      much as possible based upon objective items, related to the professional
      improvement of a nephrologist working in Hospital and following him along his
      clinical course.

PMID- 29207218
TI  - [Medicine and Nephrology from Social Networks].

PMID- 29207219
TI  - [Donor and recipient selection in living donor kidney transplantation:
      eligibility].
AB  - This review is intended to be a guide for the physician to evaluate and prepare a
      donor / recipient couple for living kidney transplantation. Although it is
      intended to be exhaustive, it will not be able to respond at all possible and
      different cases, but it may apply at most of them. Renal transplantation is
      considered the choice treatment for patients with chronic renal failure and if
      the kidney transplant is performed pre-emptive it is associated with better organ
      and patient survival. The main aim of the program is to evaluate the risks of
      donor and recipient and to ensure the donor safety and well-being. Eligibility
      for living transplant can only be granted when the risks are acceptable, well
      defined and the couple is adequately informed. The review includes clinical and
      legal procedures needed to transplantation. Early conditions that contraindicate
      the transplant must be removed, to avoid unnecessary exams, excessive waste of
      time, money. The sequence of the exams has been ordered so that costly and
      invasive surveys are carried out only after other simple and essential
      investigations have confirmed the transplant suitability. Special attention
      should be paid to the renal function measurement, proteinuria, hematuria,
      hypertension, obesity, pre diabetes, renal calculus, and cancers. To give
      eligibility for living transplant is often not easy, but a careful study can
      avoid many complications and improve the transplant outcome.

PMID- 29207220
TI  - [Long-term outcome of renal function in women with preeclampia and pregestational
      diabetes].
AB  - Pre-eclampsia (PE) is an important cause of acute renal failure and an important
      risk marker for subsequent chronic kidney disease. In normal pregnancy, there are
      marked changes in the renin-angiotensin system (RAS) including considerably
      elevated angiotensin II (ang II) levels. However, vascular resistance decreases
      markedly during normal pregnancy, suggesting that pregnant individuals are less
      sensitive to ang II than non-pregnant individuals. In contrast, during PE
      decreased circulating components of the RAS with enhanced sensitivity of ang II
      infusion have been reported. Patients with a history of PE have an increased risk
      of microalbuminuria with a prevalence similar to subjects with type 1 diabetes
      mellitus. Women with gestational or chronic hypertension were at a high risk of
      end-stage renal disease (ESRD) vs. normotensive ones, but the risk is much
      greater for women who had PE or eclampsia than those who had gestational
      hypertension only. A previous episode of PE should suggest long-term follow-up,
      especially with respect to hypertension and microalbuminuria within 6-8 weeks of
      delivery, and should require a nephrological consult if these disorders do not
      resolve. Pregestational diabetes was also associated with long-term increased
      risk of ESRD and death. Lastly, women who have PE and give birth to offspring
      with low birth weight and short gestation have a substantially increased risk for
      having a later kidney biopsy. For all these reasons, short and long-term
      evaluation of kidney function should be suggested in women with previous
      complicated pregnancy.

PMID- 29207221
TI  - [Therapy of glucocorticoid induced osteoporosis].
AB  - Glucocorticoid-induced osteoporosis (GIO) is a major cause of secondary
      osteoporosis that starts early after the beginning of therapy even for low drug
      doses. Glucocorticoids are used for the treatment of immunologic nephropathies
      and in the setting of kidney transplant. In clinical practice, a number of
      algorithms are available; they allow us to estimate the long-term risk of major
      osteoporotic fracture; but none of them is specific for GIO. To date, the
      therapeutic approach comprises both general measures aimed at correcting calcium
      and vitamin D intake, and drugs (bisphosphonates, teriparatide, hormone
      replacement therapy, denosumab) that ameliorate bone mineral density and patient
      outcomes.

PMID- 29207222
TI  - Urea and impairment of the Gut-Kidney axis in Chronic Kidney Disease.
AB  - Gut microbiota can be considered a real organ coordinating health and wellness of
      our body. It is made of more than 100 trillions of microorganisms, thus about 3
      times higher than the number of human body cells and more than 150 times than
      human genes containing 1000 different microbe species. It has been described a
      symbiotic relationship between gut and kidney, confirmed by several observations.
      This is a bi-directional relation with a mutual influence, even when kidney
      disease occurs, and consequent alterations of intestinal microbiota and
      production of uremic toxins, that in turn worsens kidney disease and its
      progression. Our review analyzes the components of gut-kidney axis and relative
      clinical consequences.

PMID- 29207223
TI  - [Fragility fracture in the Chronic Kidney Disease (CKD)].
AB  - Fragility fractures (FF) are common in patients with chronic kidney disease
      (CKD), and they occur at a younger age and with a higher frequency than in the
      general population, producing significant morbidity, mortality and healthcare
      costs. The pathogenic mechanisms underlying FF in CKD patients have not been
      completely understood. Behind CKD-MBD, the uremic toxicity should play a role in
      their pathogenesis, by affecting bone quality (uremic osteoporosis). There are
      very few prospective studies investigating risk factors for fragility fractures
      in CKD patients, and available algorithms for fracture risk prediction (FRAX and
      DeFRA) have never considered CKD. The diagnosis of vertebral fractures (FV),
      under-diagnosed in CKD patients as well as in general population, should be
      performed by Quantitative Vertebral Morphometry (QVM) both with DXA or Spine (D4
      L5) x-Ray. A recent KDIGO review has qualified the measurement of the Bone
      Mineral Density by DXA as a predictive tool for fracture risk assessment in
      patients with stage G3a-G5D. Furthermore, the Trabecular Bone Score (TBS,
      software applied to DXA) allows the bone quality evaluation as well as the
      fracture risk prediction. Other techniques, such as Quantitative Computerized
      Tomography (QCT), especially High Resolution-peripheral QCT (HR-pQCT), have been
      shown to be useful, although expensive. Finally, some bone biomarkers (PTH and
      BAP) demonstrated to be informative for the definition of fracture risk in
      patients with CKD-MBD. In conclusion, there are several different tools and
      approaches that demonstrated to be useful for the identification of CKD patients
      at high risk of fracture, when these are appropriately performed and interpreted
      by expertise clinicians.

PMID- 29207224
TI  - [Bone biopsy in the Chronic Kidney Disease (CKD)].
AB  - Histomorphometry or quantitative histology is the analysis on histologic sections
      of bone resorption, formation and structure parameters. It is the only technique
      allowing a dynamic evaluation of osteoblast activity after labelling with
      tetracycline. In addition, the use of computed image analyzer allows the
      possibility to assess bone microarchitecture. Histomorphometric bone biopsy is a
      reliable and well-tolerated procedure. Bone samples are taken at iliac crest
      level under local anesthesia and sedation. Samples are put into methyl
      metacrilate resin where the sections are prepared for the microscopic analysis of
      different histomorphometric parameters. Histomorphometry is used to exclude or
      confirm the diagnosis of osteomalacia and also to evaluate bone damage associated
      with particular treatments (for example, glucocorticoids, anticonvulsants) or in
      case of rare bone diseases (osteogenesis imperfecta). Recently, this approach has
      been repurposed for the evaluation of bone disease during Chronic Kidney Disease,
      particularly to differentiate high and low bone turnover osteodystrophy. Kidney
      Disease Improving Global Outcomes (KDIGO) guidelines have pointed out the
      situations requiring bone biopsy for histomorphometric analysis. New techniques
      using molecular biology will improve the accuracy and predictive value of this
      approach.

PMID- 29207225
TI  - [ASSOCIATION BETWEEN VERTEBRAL FRACTURES AND VASCULAR CALCIFICATIONS].
AB  - Several cross-sectional and prospective studies highlight the existence of an
      association between bone fractures and abdominal aortic calcifications,
      especially if particularly severe and independent from confounders such as aging,
      smoking habits and diabetes. This phenomenon affects not only the general
      population but also patients with chronic kidney disease in which cortical bone
      lesions are prevalent. Moreover, bone fractures and aortic calcifications have
      been proved to be linked to increased cardiovascular morbidity and mortality,
      both in the general populations and in patients with chronic kidney disease, who
      notoriously show elevated cardiovascular risks. Therefore, diagnostic
      investigations about bone fractures and abdominal aortic calcifications,
      particularly in patients with chronic kidney disease, may represent a useful tool
      for identification of patients with a higher cardiovascular risk in order to
      optimize therapies for bone metabolism disorders.

PMID- 29207226
TI  - [The treatment of the patient presenting with chronic kidney disease (CKD) and
      fragility fractures].
AB  - Fragility fractures occur in all stages of chronic kidney disease (CKD) due to
      low bone mineral density and poor bone quality (namely osteoporosis), as well as
      in CKD-mineral and bone disorders (CKD-MBD). As in postmenopausal women and older
      adults, the prompt identification of CKD subjects with a history of fragility
      fractures is crucial in order to implement strategies to reduce the risk of new
      fragility fractures and their consequences. The treatment of severe osteoporosis
      for patients with stages 1-3 CKD should not differ from patients without CKD,
      while clinical decisions and pharmacological treatments in subjects with stages 4
      5/5D CKD differ greatly, being more tricky and challenging. Before starting a
      pharmacological therapy in subjects with stages 4-5/5D CKD and a history of
      fragility fractures, it is imperative to discriminate between osteoporosis and
      CKD-MBD, using quantitative bone histomorphometry. After the implementation of
      general non-pharmacological measures for fractures and falls risk reduction, the
      management of osteoporotic patients in stages 4-5/5D CKD may include
      bisphosphonates and denosumab, though evidence for safety and efficacy is
      marginal in advanced CKD. Alendronate, risedronate and denosumab have been shown
      to be effective (in reducing fracture incidence), safe and well tolerated in
      stage 4 CKD. On the other hand, the pharmacological treatment in patients with
      stage 5/5D CKD has been explored only in small reports/series producing poor or
      limited evidence. In all cases (stages 4-5/5D), physicians should be aware of the
      potential risk of adverse events such as the adynamic bone disease or
      hypocalcaemia.

PMID- 29207227
TI  - First case report of using Ofatumumab in kidney transplantation AB0 incompatible.
AB  - Modern methods for desensitization protocol rely heavily on combined apheresis
      therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in
      AB0 incompatible kidney transplants. Severe infusion related reactions due to the
      administration of Rituximab are reported in 10% of patients. These adverse
      reactions may hinder the completion of the desensitization protocol. Therefore,
      it's useful to test alternative B cell depleting therapies. Our clinical case
      focuses on a 41-year-old male who developed an adverse infusion reaction
      following the administration of Rituximab and was given Ofatumumab as an
      alternative treatment. Ofatumumab is a fully humanized monoclonal anti-CD20
      antibody. As a fully humanized antibody, Ofatumumab may avoid immunogenic
      reactions. The patient tolerated the administration of the drug showing no signs
      of adverse side effects and with good clinical efficacy. Our case report suggest
      that Ofatumumab is a valid alternative B cell depleting agent.

PMID- 29207228
TI  - [Clinical practice for the diagnosis of cardiac arrhythmias in patients on renal
      replacement therapy: data from a Lombard survey].
AB  - Among dialysis patients, 40% of deaths are due to cardiovascular causes, and 60%
      of cardiac deaths are due to an arrhythmia. The purpose of this survey, carried
      out with the organizational support of the Lombard Section of the Italian Society
      of Nephrology, is to evaluate the frequency and mode of use of non-invasive
      instruments for the diagnosis of cardiac arrhythmias in the dialysis centers of
      Lombardy. Information on the prevalence and type of cardiac devices at December
      1, 2016 in this population was also required. Data from 18 centers were collected
      for a total of 3395 patients in replacement renal therapy, including 2907 (85.6%)
      in hemodialysis and 488 (14.4%) in peritoneal dialysis. All centers use the 12
      lead ECG in case of evocative symptoms of an arrhythmic event and 2/3 perform the
      exam with programmed cadence (usually once a year). Twenty four-hour ECG Holter
      is not used as a routine diagnostic tool. The proportion of cardiac devices is
      relatively high, compared to literature data: n=259, equal to 7.6% of the
      population. Pace-Maker patients are 166 (4.9%), those with intracardiac
      defibrillator 52 (1.5%), those with resynchronization therapy 18 (0.5%) and those
      with resynchronization therapy and intracardiac defibrillator 23 (0.7%). The
      survey provides interesting information and can be an important starting point
      for trying to optimize clinical practice and collaboration between nephrologists
      and cardiologists in front of a major problem like that of arrhythmic disease in
      patients on renal replacement therapy.

PMID- 29207230
TI  - [How italian Healthcare fights corruption: the experience of the APSS, city of
      Trento].

PMID- 29207231
TI  - [Leading characters of privacy policies, informative note and informed consent].

PMID- 29207229
TI  - [Bilirubin removal with Coupled Plasma Filtration and Adsorption in patients
      affected by hilar cholangiocarcinoma].
AB  - Background: Patients affected by hilar cholangiocarcinoma are eligible for
      surgery only in the 20-30% of the cases and postoperative mortality is 40-50%.
      Many specialists are involved in the treatment of this disease, like surgeons,
      gastroenterologists, oncologists and radiotherapists. Recent studies have shown
      that preoperative bilirubinaemia is a predictor of morbidity and mortality after
      surgery. Coupled Plasma Filtration and Adsorption (CPFA) is a blood purification
      extracorporeal therapy recommended for sepsis and able to reduce bilirubinaemia.
      METHODS: We treated 10 patients referred to our centre affected by hilar
      cholangiocarcinoma complicated by obstructive jaundice with 34 CPFA sessions to
      test its ability to reduce preoperative bilirubin levels and we checked for
      mortality at 90 days. RESULTS: CPFA reduced preoperative bilirubin of 30% for
      session; it also improved others inflammation and coagulation tests. Mortality at
      90 days was 40%. CONCLUSIONS: CPFA is an effective therapy for
      hyperbilirubinaemia. Lowering preoperative bilirubinaemia and improvement of
      coagulation tests subsidized the management of the patients but in our study did
      not affect postoperative mortality. Further studies to evaluate the indications
      for treatments that remove bilirubin in this setting are needed.

PMID- 29207232
TI  - A- to B-DNA Transition in AMBER Force Fields and Its Coupling to Sugar Pucker.
AB  - The A/B transition is a basic element of DNA conformational change. Because of
      its involvement in the sensing of the ionic conditions by DNA and in specific
      protein-DNA interactions, this transition is important for biological functions
      of DNA. Therefore, accurate modeling of the A/B equilibrium by means of empirical
      force fields is of utmost interest. In this work, we examine the A/B equilibrium
      in three AMBER force fields, including the recent bsc1 and OL15 modifications,
      using much longer MD simulations than attempted before. Special attention is paid
      to the coupling of the A/B equilibrium with the south/north (S/N) transition of
      the sugar pucker. We found that none of the tested force fields provided a
      satisfactory description of the A/B equilibrium because the B-form was predicted
      to be much too stable and the A-form was predicted to be almost absent even in
      concentrated trifluoroethanol solutions. Based on comparison with NMR data for
      duplexes and single nucleosides, we hypothesize that this problem arose from the
      incorrect description of the S/N equilibrium of sugar pucker, where the south
      conformation is much too stable, thus stabilizing the B-form. Because neither the
      A/B equilibrium in duplexes nor the S/N equilibrium in nucleosides was described
      accurately, further refinements of the AMBER DNA force fields are needed.

PMID- 29207233
TI  - Anomalous Temperature Dependence in Metal-Black Phosphorus Contact.
AB  - Metal-semiconductor contact has been the performance limiting problem for
      electronic devices and also dictates the scaling potential for future generation
      devices based on novel channel materials. Two-dimensional semiconductors beyond
      graphene, particularly few layer black phosphorus, have attracted much attention
      due to their exceptional electronic properties such as anisotropy and high
      mobility. However, due to its ultrathin body nature, few layer black phosphorus
      metal contact behaves differently than conventional Schottky barrier (SB)
      junctions, and the mechanisms of its carrier transport across such a barrier
      remain elusive. In this work, we examine the transport characteristic of metal
      black phosphorus contact under varying temperature. We elucidated the origin of
      apparent negative SB heights extracted from classical thermionic emission model
      and also the phenomenon of metal-insulator transition observed in the current
      temperature transistor characteristic. In essence, we found that the SB height
      can be modulated by the back-gate voltage, which beyond a certain critical point
      becomes so low that the injected carrier can no longer be described by the
      conventional thermionic emission theory. The transition from transport dominated
      by a Maxwell-Boltzmann distribution for the high energy tail states, to that of a
      Fermi distribution by low energy Fermi sea electrons, is the physical origin of
      the observed metal-insulator transition. We identified two distinctive tunneling
      limited transport regimes in the contact: vertical and longitudinal tunneling.

PMID- 29207234
TI  - Vacuum UV Polarization Spectroscopy of p-Terphenyl.
AB  - p-Terphenyl is used as a component in a variety of optical devices. In this
      investigation, the electronic transitions of p-terphenyl are investigated by
      synchrotron radiation linear dichroism (SRLD) spectroscopy in the range 30000
      58000 cm-1 (330-170 nm) on molecular samples aligned in stretched polyethylene,
      thereby extending the region investigated by polarization spectroscopy into the
      vacuum UV. The resulting partial absorbance curves reveal that the vacuum UV band
      system with a maximum at 55000 cm-1 (180 nm) is predominantly short axis
      polarized. This result is of interest in the optical applications of p-terphenyl,
      for example as a wavelength shifter. The observed polarization spectra are
      compared with the results of quantum chemical model calculations. Convoluted
      versions of the transitions predicted with the semiempirical ZINDO method and
      with the long-range-corrected time-dependent density functional theory (TD-DFT)
      procedures TD-CAM-B3LYP, TD-LC-omegaPBE, and TD-omegaB97XD are in similar
      qualitative agreement with the observed partial absorbance curves throughout the
      investigated spectral regions, while TD-B3LYP fails to predict qualitatively the
      spectrum of p-terphenyl in the region above 40000 cm-1 (250 nm).

PMID- 29207235
TI  - A Data-Driven Perspective on the Hierarchical Assembly of Molecular Structures.
AB  - Macromolecular systems are composed of a very large number of atomic degrees of
      freedom. There is strong evidence suggesting that structural changes occurring in
      large biomolecular systems at long time scale dynamics may be captured by models
      coarser than atomistic, although a suitable or optimal coarse-graining is a
      priori unknown. Here we propose a systematic approach to learning a coarse
      representation of a macromolecule from microscopic simulation data. In
      particular, the definition of effective coarse variables is achieved by
      partitioning the degrees of freedom both in the structural (physical) space and
      in the conformational space. The identification of groups of microscopic
      particles forming dynamical coherent states in different metastable states leads
      to a multiscale description of the system, in space and time. The application of
      this approach to the folding dynamics of two proteins provides a revised view of
      the classical idea of prestructured regions (foldons) that combine during a
      protein-folding process and suggests a hierarchical characterization of the
      assembly process of folded structures.

PMID- 29207236
TI  - Modified Separator Performing Dual Physical/Chemical Roles to Inhibit Polysulfide
      Shuttle Resulting in Ultrastable Li-S Batteries.
AB  - In this paper we describe a modified (AEG/CH) coated separator for Li-S batteries
      in which the shuttling phenomenon of the lithium polysulfides is restrained
      through two types of interactions: activated expanded graphite (AEG) flakes
      interacted physically with the lithium polysulfides, while chitosan (CH), used to
      bind the AEG flakes on the separator, interacted chemically through its abundance
      of amino and hydroxyl functional groups. Moreover, the AEG flakes facilitated
      ionic and electronic transfer during the redox reaction. Live H-cell discharging
      experiments revealed that the modified separator was effective at curbing
      polysulfide shuttling; moreover, X-ray photoelectron spectroscopy analysis of the
      cycled separator confirmed the presence of lithium polysulfides in the AEG/CH
      matrix. Using this dual functional interaction approach, the lifetime of the pure
      sulfur-based cathode was extended to 3000 cycles at 1C-rate (1C = 1670 mA/g),
      decreasing the decay rate to 0.021% per cycle, a value that is among the best
      reported to date. A flexible battery based on this modified separator exhibited
      stable performance and could turn on multiple light-emitting diodes. Such
      modified membranes with good mechanical strength, high electronic conductivity,
      and anti-self-discharging shield appear to be a scalable solution for future high
      energy battery systems.

PMID- 29207238
TI  - Nonadiabatic Ab Initio Molecular Dynamics with the Floating Occupation Molecular
      Orbital-Complete Active Space Configuration Interaction Method.
AB  - We show that the floating occupation molecular orbital complete active space
      configuration interaction (FOMO-CASCI) method is a promising alternative to the
      widely used complete active space self-consistent field (CASSCF) method in direct
      nonadiabatic dynamics simulations. We have simulated photodynamics of three
      archetypal molecules in photodynamics: ethylene, methaniminium cation, and
      malonaldehyde. We compared the time evolution of electronic populations and
      reaction mechanisms as revealed by the FOMO-CASCI and CASSCF approaches.
      Generally, the two approaches provide similar results. Some dynamical differences
      are observed, but these can be traced back to energetically minor differences in
      the potential energy surfaces. We suggest that the FOMO-CASCI method represents,
      due to its efficiency and stability, a promising approach for direct ab initio
      dynamics in the excited state.

PMID- 29207239
TI  - The Human Microbiota, Infectious Disease, and Global Health: Challenges and
      Opportunities.
AB  - Despite significant advances in treating infectious diseases worldwide, morbidity
      and mortality associated with pathogen infection remains extraordinarily high and
      represents a critical scientific and global health challenge. Current strategies
      to combat these infectious agents include a combination of vaccines, small
      molecule drugs, increased hygiene standards, and disease-specific interventions.
      While these approaches have helped to drastically reduce the incidence and number
      of deaths associated with infection, continued investment in current strategies
      and the development of novel therapeutic approaches will be required to address
      these global health threats. Recently, human- and vector-associated microbiotas,
      the assemblages of microorganisms living on and within their hosts, have emerged
      as a potentially important factor mediating both infection risk and disease
      progression. These complex microbial communities are involved in intricate and
      dynamic interactions with both pathogens as well as the innate and adaptive
      immune systems of their hosts. Here, we discuss recent findings that have
      illuminated the importance of resident microbiotas in infectious disease,
      emphasizing opportunities for novel therapeutic intervention and future
      challenges for the field. Our discussion will focus on four major global health
      threats: tuberculosis, malaria, HIV, and enteric/diarrheal diseases. We hope this
      Perspective will highlight the many opportunities for chemists and chemical
      biologists in this field as well as inspire efforts to elucidate the mechanisms
      underlying established disease correlations, identify novel microbiota-based risk
      factors, and develop new therapeutic interventions.

PMID- 29207240
TI  - C(5) Site-Selective Functionalization of (S)-Cotinine.
AB  - (S)-(-)-Cotinine 2 undergoes direct and site-selective iridium-catalyzed
      borylation to provide boronate ester 3 and bromide 4 which offer flexible entry
      to a range of C(5)-substituted cotinine variants.

PMID- 29207237
TI  - Proteins and Proteoforms: New Separation Challenges.

PMID- 29207241
TI  - Quantum Wires and Waveguides Formed in Graphene by Strain.
AB  - Confinement of electrons in graphene to make devices has proven to be a
      challenging task. Electrostatic methods fail because of Klein tunneling, while
      etching into nanoribbons requires extreme control of edge terminations, and
      bottom-up approaches are limited in size to a few nanometers. Fortunately, its
      mechanical flexibility raises the possibility of using strain to alter graphene's
      properties and create novel straintronic devices. Here, we report transport
      studies of nanowires created by linearly-shaped strained regions resulting from
      individual folds formed by layer transfer onto hexagonal boron nitride.
      Conductance measurements across the folds reveal Coulomb blockade signatures,
      indicating confined charges within these structures, which act as quantum dots.
      Along folds, we observe sharp features in traverse resistivity measurements,
      attributed to an amplification of the dot conductance modulations by a resistance
      bridge incorporating the device. Our data indicates ballistic transport up to ~1
      MUm along the folds. Calculations using the Dirac model including strain are
      consistent with measured bound state energies and predict the existence of valley
      polarized currents. Our results show that graphene folds can act as straintronic
      quantum wires.

PMID- 29207242
TI  - Suppression of Aflatoxin Production in Aspergillus Species by Selected Peanut
      (Arachis hypogaea) Stilbenoids.
AB  - Aspergillus flavus is a soil fungus that commonly invades peanut seeds and often
      produces carcinogenic aflatoxins. Under favorable conditions, the fungus
      challenged peanut plant produces and accumulates resveratrol and its prenylated
      derivatives in response to such an invasion. These prenylated stilbenoids are
      considered peanut antifungal phytoalexins. However, the mechanism of peanut
      fungus interaction has not been sufficiently studied. We used pure peanut
      stilbenoids arachidin-1, arachidin-3, and chiricanine A to study their effects on
      the viability of and metabolite production by several important toxigenic
      Aspergillus species. Significant reduction or virtually complete suppression of
      aflatoxin production was revealed in feeding experiments in A. flavus,
      Aspergillus parasiticus, and Aspergillus nomius. Changes in morphology, spore
      germination, and growth rate were observed in A. flavus exposed to the selected
      peanut stilbenoids. Elucidation of the mechanism of aflatoxin suppression by
      peanut stilbenoids could provide strategies for preventing plant invasion by the
      fungi that produce aflatoxins.

PMID- 29207243
TI  - Significantly Enhanced Dielectric Performances and High Thermal Conductivity in
      Poly(vinylidene fluoride)-Based Composites Enabled by SiC@SiO2 Core-Shell
      Whiskers Alignment.
AB  - Design of composites with ordered fillers arrangement results in anisotropic
      performances with greatly enhanced properties along a specific direction, which
      is a powerful tool to optimize physical properties of composites. Well-aligned
      core-shell SiC@SiO2 whiskers in poly(vinylidene fluoride) (PVDF) matrix has been
      achieved via a modified spinning approach. Because of the high aspect ratio of
      SiC whiskers, strong anisotropy and significant enhancement in dielectric
      constant were observed with permittivity 854 along the parallel direction versus
      71 along the perpendicular direction at 20 vol % SiC@SiO2 loading, while little
      increase in dielectric loss was found due to the highly insulating SiO2 shell.
      The anisotropic dielectric behavior of the composite is perfectly understood
      macroscopically to have originated from anisotropic intensity of interfacial
      polarization based on an equivalent circuit model of two parallel RC circuits
      connected in series. Furthermore, finite element simulations on the three
      dimensional distribution of local electric field, polarization, and leakage
      current density in oriented SiC@SiO2/PVDF composites under different applied
      electrical field directions unambiguously revealed that aligned core-shell
      SiC@SiO2 whiskers with a high aspect ratio significantly improved dielectric
      performances. Importantly, the thermal conductivity of the composite was
      synchronously enhanced over 7 times as compared to that of PVDF matrix along the
      parallel direction at 20 vol % SiC@SiO2 whiskers loading. This study highlights
      an effective strategy to achieve excellent comprehensive properties for high-k
      dielectrics.

PMID- 29207244
TI  - Chemoproteomics Reveals Unexpected Lysine/Arginine-Specific Cleavage of Peptide
      Chains as a Potential Protein Degradation Machinery.
AB  - Proteins can undergo oxidative cleavage by in vitro metal-catalyzed oxidation
      (MCO) in either the alpha-amidation or the diamide pathway. However, whether
      oxidative cleavage of polypeptide-chain occurs in biological systems remains
      unexplored. We describe a chemoproteomic approach to globally and site
      specifically profile electrophilic protein degradants formed from peptide
      backbone cleavages in human proteomes, including the known N-terminal alpha
      ketoacyl products and >1000 unexpected N-terminal formyl products. Strikingly,
      such cleavages predominantly occur at the carboxyl side of lysine (K) and
      arginine (R) residues across native proteomes in situ, while MCO-induced
      oxidative cleavages randomly distribute on peptide/protein sequences in vitro.
      Furthermore, ionizing radiation-induced reactive oxygen species (ROS) also
      generate random oxidative cleavages in situ. These findings suggest that the
      endogenous formation of N-formyl and N-alpha-ketoacyl degradants in biological
      systems is more likely regulated by a previously unknown mechanism with a trypsin
      like specificity, rather than the random oxidative damage as previously thought.
      More generally, our study highlights the utility of quantitative chemoproteomics
      in combination with unrestricted search tools as a viable strategy to discover
      unexpected chemical modifications of proteins labeled with active-based probes.

PMID- 29207245
TI  - Mixed Quantum/Classical Method for Nonadiabatic Quantum Dynamics in Explicit
      Solvent Models: The pipi*/npi* Decay of Thymine in Water as a Test Case.
AB  - We present a novel mixed quantum classical dynamical method to include solvent
      effects on internal conversion (IC) processes. All the solute degrees of freedom
      are represented by a wavepacket moving according to nonadiabatic quantum
      dynamics, while the motion of an explicit solvent model is described by an
      ensemble of classical trajectories. The mutual coupling of the solute and solvent
      dynamics is included within a mean-field framework and the quantum and classical
      equations of motions are solved simultaneously. As a test case we apply our
      method to the ultrafast pipi* -> npi* decay of thymine in water. Solvent
      dynamical response modifies IC yield already on the 50 fs time scale. This effect
      is due to water librational motions that stabilize the most populated state. Pure
      static disorder, that is, the existence of different solvent configurations when
      photoexcitation takes place, also has a remarkable impact on the dynamics.

PMID- 29207246
TI  - Multiple Reaction Monitoring for the Quantitation of Serum Protein Glycosylation
      Profiles: Application to Ovarian Cancer.
AB  - Protein glycosylation fingerprints are widely recognized as potential markers for
      disease states, and indeed differential glycosylation has been identified in
      multiple types of autoimmune diseases and several types of cancer. However,
      releasing the glycans leave the glycoproteins unknown; therefore, there exists a
      need for high-throughput methods that allow quantification of site- and protein
      specific glycosylation patterns from complex biological mixtures. In this study,
      a targeted multiple reaction monitoring (MRM)-based method for the protein- and
      site-specific quantitation involving serum proteins immunoglobulins A, G and M,
      alpha-1-antitrypsin, transferrin, alpha-2-macroglobulin, haptoglobin, alpha-1
      acid glycoprotein and complement C3 was developed. The method is based on tryptic
      digestion of serum glycoproteins, followed by immediate reverse phase UPLC-QQQ-MS
      analysis of glycopeptides. To quantitate protein glycosylation independent of the
      protein serum concentration, a nonglycosylated peptide was also monitored. Using
      this strategy, 178 glycopeptides and 18 peptides from serum glycoproteins are
      analyzed with good repeatability (interday CVs of 3.65-21-92%) in a single 17 min
      run. To assess the potential of the method, protein glycosylation was analyzed in
      serum samples from ovarian cancer patients and controls. A training set
      consisting of 40 cases and 40 controls was analyzed, and differential analyses
      were performed to identify aberrant glycopeptide levels. All findings were
      validated in an independent test set (n = 44 cases and n = 44 controls). In
      addition to the differential glycosylation on the immunoglobulins, which was
      reported previously, aberrant glycosylation was also observed on each of the
      glycoproteins, which could be corroborated in the test set. This report shows the
      development of a method for targeted protein- and site-specific glycosylation
      analysis and the potential of such methods in biomarker development.

PMID- 29207247
TI  - Surface Micropatterning of Uniaxially Oriented Polyethylene Films Using
      Interference Holography for Strain Sensors.
AB  - A new procedure is presented for direct generation of surface micropatterns on
      uniaxially oriented polyethylene (PE) films using interference holography with a
      nanosecond pulsed laser. An ultraviolet absorber, 2-(2H-benzotriazol-2-yl)-4,6-di
      tert-pentylphenol (BZT) is incorporated into PE prior to stretching to generate
      absorption at the wavelength of the laser. Illumination with an interference
      pattern in the absorption band of BZT leads to an obvious height variation in the
      exposed regions and consequently relief gratings are generated. The height in the
      exposed regions is strongly dependent on the angle between the grating direction
      and the film orientation direction. This phenomenon is attributed to a
      combination of events such as melting, entropic contraction, recrystallization,
      thermal evaporation of BZT, and anisotropic thermal conductivity. It is shown
      that the relief height increases with increasing BZT concentration and exhibits a
      linear dependence on the energy dose above a certain threshold. Additionally, the
      oriented PE films with the surface micropatterns are explored for strain sensors.
      The results demonstrate that small strains below 10% are monitored accurately in
      tensile deformation of the micropatterned, oriented PE films which makes these
      films potentially useful as strain sensors.

PMID- 29207248
TI  - Effect of pH and Salt on Surface pKa of Phosphatidic Acid Monolayers.
AB  - The pH-induced surface speciation of organic surfactants such as fatty acids and
      phospholipids in monolayers and coatings is considered to be an important factor
      controlling their interfacial organization and properties. Yet, correctly
      predicting the surface speciation requires the determination of the surface
      dissociation constants (surface pKa) of the protic functional group(s) present.
      Here, we use three independent methods-compression isotherms, surface tension pH
      titration, and infrared reflection-absorption spectroscopy (IRRAS)-to study the
      protonation state of dipalmitoylphosphatidic acid (DPPA) monolayers on water and
      NaCl solutions. By examining the molecular area expansion at basic pH, the pKa to
      remove the second proton of DPPA (surface pKa2) at the aqueous interface is
      estimated. In addition, utilizing IRRAS combined with density functional theory
      calculations, the vibrational modes of the phosphate headgroup were directly
      probed and assigned to understand DPPA charge speciation with increasing pH. We
      find that all three experimental techniques give consistent surface pKa2 values
      in good agreement with each other. Results show that a condensed DPPA monolayer
      has a surface pKa2 of 11.5, a value higher than previously reported (~7.9-8.5).
      This surface pKa2 was further altered by the presence of Na+ cations in the
      aqueous subphase, which reduced the surface pKa2 from 11.5 to 10.5. It was also
      found that the surface pKa2 value of DPPA is modulated by the packing density
      (i.e., the surface charge density) of the monolayer, with a surface pKa2 as low
      as 9.2 for DPPA monolayers in the two-dimensional gaseous phase over NaCl
      solutions. The experimentally determined surface pKa2 values are also found to be
      in agreement with those predicted by Gouy-Chapman theory, validating these
      methods and proving that surface charge density is the driving factor behind
      changes to the surface pKa2.

PMID- 29207249
TI  - Preschoolers' health-related quality of life following the implementation of a
      childcare physical activity intervention.
AB  - Being active offers many physical and emotional benefits contributing to a higher
      health-related quality of life (HRQoL); however, this relationship remains
      unexplored among preschoolers (aged 2.5-5 years). This study examined the impact
      of the Supporting Physical Activity in the Childcare Environment (SPACE), which
      was an intervention implemented using a cluster randomized controlled trial on
      preschoolers' HRQoL. Childcare centres were randomly allocated to the
      experimental (n = 11) or control (n = 11) conditions, and preschoolers' HRQoL was
      measured using the parent-report Pediatric Quality of Life Inventory 4.0 (3
      subscales: physical, psychosocial, and total HRQoL) at baseline, post
      intervention (i.e., week 8), and 6- and 12-month follow-up. A linear mixed
      effects model was used to determine if preschoolers in the experimental condition
      displayed an increased HRQoL post-intervention and at follow-up compared with
      preschoolers in the control condition. Preschoolers (n = 234) with HRQoL data at
      baseline and one additional time-point were retained for analyses. Body mass
      index was not found to impact significantly on the intervention, and no
      statistically significant interaction effects were found for any of the 3 HRQoL
      variables. In conclusion, the SPACE intervention had no impact on preschoolers'
      HRQoL. Given the scarcity of research in this population, additional exploration
      is necessary to better understand the potential impact of physical activity
      participation on preschoolers' HRQoL.

PMID- 29207250
TI  - A survey of dog and cat anaesthesia in a sample of veterinary practices in New
      Zealand.
AB  - AIMS: To survey current anaesthesia practices for dogs and cats in small and
      mixed animal practices in New Zealand in order to improve anaesthesia education.
      METHODS: A questionnaire was sent to 440 small and mixed animal practices,
      including questions regarding the type of practice, preanaesthetic examination,
      anaesthetic drugs and management, anaesthetic machines, monitoring and topics of
      interest for continuing professional development. RESULTS: Responses were
      obtained from 113/440 (26%) practices, with 78 (69%) respondents from small and
      35 (31%) from mixed animal practices. A preanaesthetic physical examination was
      carried out by >95% of respondents and premedication was usually given to dogs
      (112/113; 99%) and cats (95/113; 85%). Acepromazine was the preferred sedative
      for dogs and cats, with morphine or buprenorphine. Propofol and alfaxalone were
      the preferred induction agents, and isoflurane was preferred for maintenance in
      both dogs and cats. A venous catheter was usually placed for anaesthesia in dogs
      (59/113; 52%), but less so in cats (39/113; 35%). Perioperative fluid was
      administered at 10 mL/kg/hour by 62/110 (56%) respondents. Intubation was usually
      used for anaesthesia in dogs (111/112; 99%), and cats (87/112; 78%). Almost 40%
      of respondents usually administered supplementary oxygen if patients were not
      intubated. Local analgesia was used by 69/111 (88%) respondents sometimes or
      always if applicable. Morphine or buprenorphine, and meloxicam were common
      choices for post-operative analgesia after neuter surgery in dogs and cats. A
      semiclosed (non-rebreathing) system was used in animals weighing <10 kg, and a
      Mapleson E or F non-rebreathing circuit was used by 66/109 (61%) practices. Only
      15/111 (14%) practices had a ventilator in their practice. A dedicated
      anaesthetist was usually used by 104/113 (92%) practices, and apnoea alarms,
      pulse oximeters, thermometers and oesophageal stethoscopes were the main
      monitoring devices available in practices. Loco-regional block, pain management,
      and anaesthetic drugs were the main topics of interest for continuing education.
      CONCLUSIONS AND CLINICAL RELEVANCE: Responses by the veterinarians taking part in
      this survey indicated that they had a reasonably good standard of anaesthetic
      practice. A physical examination was carried out preanaesthesia, and
      premedication including analgesia was routinely administered to most patients. A
      dedicated anaesthetist usually monitored patients and most respondents reported
      they had access to basic anaesthetic monitoring equipment. Areas where changes
      could lead to improved anaesthetic practice were increased use of I/V
      catheterisation, endotracheal intubation, and supplementary oxygen, and reduced
      I/V fluid rates.

PMID- 29207251
TI  - Oral contraceptives modulate the muscle metaboreflex in healthy young women.
AB  - There are known sex differences in blood pressure regulation. The differences are
      related to ovarian hormones that influence beta-adrenergic receptors and the
      transduction of muscle sympathetic nerve activity. Oral contraceptives (OC)
      modulate the ovarian hormonal profile in women and therefore may alter the
      cardiovascular response. We questioned if OC would alter the absolute pressor
      response to static exercise and influence the day-to-day variability of the
      response. Healthy men (n = 11) and women (n = 19) completed a familiarization day
      and 2 experimental testing days. Women were divided into those taking (W-OC, n =
      10) and not taking (W-NC, n = 9) OC. Each experimental testing day involved
      isometric handgripping exercise, at 30% of maximal force, followed by circulatory
      occlusion to isolate the metaboreflex. Experimental days in men were 7-14 days
      apart. The first experimental testing in W-OC occurred 2-7 days after the start
      of the active phase of their OC. Women not taking OC were tested during the early
      and late follicular phase of the menstrual cycle as determined by commercial
      ovulation monitor. The increase in mean arterial pressure (MAP) during exercise
      was significantly lower in W-NC (95 +/- 4 mm Hg) compared with men (114 +/- 4 mm
      Hg) and W-OC (111 +/- 3 mm Hg) (P < 0.05), with the differences preserved during
      circulatory occlusion. The rise in MAP was significantly correlated between the 2
      testing days in men (r = 0.72, P < 0.01) and W-OC (r = 0.77, P < 0.05), but not
      in W-NC (r = 0.17, P = 0.67), indicating greater day-to-day variation in W-NC. In
      conclusion, OC modulate the exercise pressor response in women and minimize day
      to-day variability in the exercise metaboreflex.

PMID- 29207252
TI  - Role of activin C in normal ovaries and granulosa cell tumours of mice and
      humans.
AB  - Activins and inhibins play important roles in the development, growth and
      function of the ovary. Mice lacking inhibin develop granulosa cell tumours in
      their ovaries that secrete activin A, and these tumours are modulated by
      increased activin C expression. The aim of the present study was to identify
      where activin C is expressed in mouse and human ovaries and whether
      overexpression of activin C modulates normal follicular development in mice.
      Immunohistochemical staining for the activin betaC subunit was performed on
      sections from mouse and human ovaries and human adult granulosa cell tumours.
      Stereology techniques were used to quantify oocyte and follicular diameters, and
      the percentage of different follicular types in ovaries from wild-type mice and
      those underexpressing inhibin alpha and/or overexpressing activin C. Staining for
      activin betaC was observed in the oocytes, granulosa cells, thecal cells and
      surface epithelium of mouse and human ovaries, and in the granulosa-like cells of
      adult granulosa cell tumours. Overexpression of activin C in mice did not alter
      follicular development compared with wild-type mice, but it did modulate the
      development of abnormal early stage follicles in inhibin alpha-null mice. These
      results provide further evidence of a role for activin C in the ovary.

PMID- 29207253
TI  - Influence of postnatal prolactin modulation on the development and maturation of
      ventral prostate in young rats.
AB  - Besides androgenic dependence, other hormones also influence the prostate
      biology. Prolactin has been described as an important hormone associated with
      maintenance of prostatic morphophysiology; however, there is a lack of
      information on the involvement of prolactin during prostate development and
      growth. This study aimed to evaluate whether perinatal prolactin modulation
      interferes with rat ventral prostate (VP) development and maturation. Therefore,
      prolactin or bromocriptine (an inhibitor of prolactin release from the pituitary)
      were administered to Sprague Dawley rats from postnatal Day (PND) 12 to PND 21 or
      35. Animals were then killed and serum hormonal quantification, VP morphological
      stereological and immunohistochemical analyses and western blotting reactions
      were employed. Our results demonstrate that prolactin blockage increased serum
      testosterone on PND 21, which reflected an increase in anogenital distance.
      Although prolactin modulation did not interfere with VP weight, it modified VP
      morphology by dilating the acinar lumen and reducing epithelial cell height.
      Prolactin activated the signal transducer and activator of transcription (STAT)
      downstream pathway, increased androgen receptor expression and epithelial
      proliferation. In addition, prolactin and bromocriptine also increased expression
      of cytokeratin 18, a marker of luminal-differentiated cells. In conclusion, the
      VP responds to prolactin modulation through a mechanism of increasing the
      epithelial proliferative response and dynamics of cell differentiation,
      especially in animals treated for a more prolonged period.

PMID- 29207254
TI  - Seeing a Coastline Paradox in Membrane Reservoirs.
AB  - In this issue of Developmental Cell, Goudarzi et al. (2017) examine the membrane
      source that allows bleb-based cell migration in vivo. Their work reminds us of
      the fractal nature of cell surfaces and highlights how the unfolding of these
      convoluted surfaces contributes to physiologically relevant cell shape change in
      intact organisms.

PMID- 29207255
TI  - Macrophage Cytoplasmic Transfer in Melanoma Invasion.
AB  - Within tumors, macrophage infiltration can promote cancer cell invasiveness and,
      consequently, metastatic dissemination. In this issue of Developmental Cell, Roh
      Johnson et al. (2017) reveal that cytoplasmic transfer from macrophages to
      melanoma cells correlates with melanoma invasion and arises as a result of
      intimate cell-cell contact.

PMID- 29207256
TI  - MAP Kinase Signaling Turns to ICE.
AB  - Plants in temperate climates utilize cold acclimation modes to improve frost
      tolerance during phases of active growth. Two papers in this issue of
      Developmental Cell (Li et al., 2017; Zhao et al., 2017) now highlight the
      important role MAP kinases play in this process in Arabidopsis thaliana.

PMID- 29207257
TI  - Forcing Entry into the Nucleus.
AB  - Nuclear pore complexes tightly regulate nucleo-cytoplasmic transport, controlling
      the nuclear concentration of several transcription factors. In a recent issue of
      Cell, Elosegui-Artola et al. (2017) show that nuclear deformation modulates the
      nuclear entry rates of YAP/TAZ via nuclear pore stretching, clarifying how forces
      affect gene transcription.

PMID- 29207258
TI  - Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo.
AB  - Interactions between tumor cells and tumor-associated macrophages play critical
      roles in the initiation of tumor cell motility. To capture the cellular
      interactions of the tumor microenvironment with high-resolution imaging, we
      directly visualized tumor cells and their interactions with macrophages in
      zebrafish. Live imaging in zebrafish revealed that macrophages are dynamic, yet
      maintain sustained contact with tumor cells. In addition, the recruitment of
      macrophages to tumor cells promotes tumor cell dissemination. Using a Cre/LoxP
      strategy, we found that macrophages transfer cytoplasm to tumor cells in
      zebrafish and mouse models. Remarkably, macrophage cytoplasmic transfer
      correlated with melanoma cell dissemination. We further found that macrophages
      transfer cytoplasm to tumor cells upon cell contact in vitro. Thus, we present a
      model in which macrophage/tumor cell contact allows for the transfer of
      cytoplasmic molecules from macrophages to tumor cells corresponding to increased
      tumor cell motility and dissemination.

PMID- 29207259
TI  - A Chemical-Genetic Approach Reveals the Distinct Roles of GSK3alpha and GSK3beta
      in Regulating Embryonic Stem Cell Fate.
AB  - Glycogen synthase kinase 3 (GSK3) plays a central role in diverse cellular
      processes. GSK3 has two mammalian isozymes, GSK3alpha and GSK3beta, whose
      functions remain ill-defined because of a lack of inhibitors that can distinguish
      between the two highly homologous isozymes. Here, we show that GSK3alpha and
      GSK3beta can be selectively inhibited in mouse embryonic stem cells (ESCs) using
      a chemical-genetic approach. Selective inhibition of GSK3beta is sufficient to
      maintain mouse ESC self-renewal, whereas GSK3alpha inhibition promotes mouse ESC
      differentiation toward neural lineages. Genome-wide transcriptional analysis
      reveals that GSK3alpha and GSK3beta have distinct sets of downstream targets.
      Furthermore, selective inhibition of individual GSK3 isozymes yields distinct
      phenotypes from gene deletion, highlighting the power of the chemical-genetic
      approach in dissecting kinase catalytic functions from the protein's scaffolding
      functions. Our study opens new avenues for defining GSK3 isozyme-specific
      functions in various cellular processes.

PMID- 29207261
TI  - PARPs.
AB  - Leung introduces the various roles of PARPs and the regulation of ADP
      ribosylation of protein substrates.

PMID- 29207262
TI  - Transcranial electrical stimulation.
AB  - Transcranial electrical stimulation (tES) is a neuromodulatory technique in which
      low voltage constant or alternating currents are applied to the human brain via
      scalp electrodes. The basic idea of tES is that the application of weak currents
      can interact with neural processing, modify plasticity and entrain brain
      networks, and that this in turn can modify behaviour. The technique is now widely
      employed in basic and translational research, and increasingly is also used
      privately in sport, the military and recreation. The proposed capacity to augment
      recovery of brain function, by promoting learning and facilitating plasticity,
      has motivated a burgeoning number of clinical trials in a wide range of disorders
      of the nervous system.

PMID- 29207260
TI  - A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell
      Survival and Affects Organ Size.
AB  - The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell
      proliferation and survival, but interactions between these parallel control
      systems are poorly defined. In this study, we demonstrate that interaction
      between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby
      suppresses Yki target gene expression. RBF modifies these effects by reducing
      E2F1/Sd interaction. This regulation has significant effects on apoptosis, organ
      size, and progenitor cell proliferation. Using a combination of DamID-seq and RNA
      seq, we identified a set of Yki targets that play a diversity of roles during
      development and are suppressed by E2F1. Further, we found that human E2F1
      competes with YAP for TEAD1 binding, affecting YAP activity, indicating that this
      mode of cross-regulation is conserved. In sum, our study uncovers a previously
      unknown mechanism in which RBF and E2F1 modify Hippo signaling responses to
      modulate apoptosis, organ growth, and homeostasis.

PMID- 29207263
TI  - Ocean sunfish as indicators for the 'rise of slime'.
AB  - Overfishing and ocean warming are drastically altering the community composition
      and size structure of marine ecosystems, eliminating large bodied species [1].
      Against a backdrop of such environmental change, the heaviest of all bony fish,
      the ocean sunfish (Mola mola), seems an improbable survivor. Indeed this indolent
      giant is killed globally as bycatch, and is listed as 'Vulnerable'[2]. We
      undertook the most extensive aerial surveys of sunfish ever conducted and found
      surprisingly high abundances off the Atlantic and Mediterranean coasts of Western
      Europe. With up to 475 individuals per 100 km2, these figures are one order of
      magnitude higher than abundance estimates for other areas [3-5]. Using
      bioenergetic modelling, we estimate that each sunfish requires 71 kg day-1 of
      jellyfish, a biomass intake more than an order of magnitude greater than
      predicted for a similarly sized teleost. Scaled up to the population level, this
      equates to a remarkable 20,774 tonnes day-1 of predated jellyfish across our
      study area in summer. Sunfish abundance may be facilitated by overfishing and
      ocean warming, which together cause reduced predation of sunfish by sharks and
      elevated jellyfish biomass. Our combined survey and bioenergetic data provide the
      first-ever estimate of spatialized ocean sunfish daily food requirements, and
      stress the importance of this species as a global indicator for the 'rise of
      slime'. This hypothesis posits that, in an overfished world ocean exposed to
      global warming, gelatinous zooplankton should flourish, to the detriment of other
      mesotrophic species such as small pelagic fish, causing irreversible trophic
      cascades as well as a series of other environmental and economic issues.

PMID- 29207264
TI  - Non-cortical magnitude coding of space and time by pigeons.
AB  - Considerable research in cognitive science, neuroscience, and developmental
      science has revealed that the temporal, spatial, and numerical features of a
      stimulus can interact with one another [1,2], as when larger stimuli are
      perceived as lasting longer than smaller stimuli. These findings have inspired
      the prominent hypothesis that time, space, and number are processed by a 'common
      magnitude system', which represents these dimensions via the same unit of
      magnitude [3,4]. According to current theorizing, the parietal cortex mediates
      this system [4]. To test the species generality and neuroanatomical foundations
      of this hypothesis, we asked whether space-time interactions can be observed in
      birds. Unlike mammals, birds lack a cortex [5,6]; rather, they possess a neuron
      dense pallium that is organized in clusters, in contrast to the laminar structure
      of the mammalian cortex [7]. Despite these striking neuroanatomical disparities,
      we observed reliable space-time interactions in pigeons. Our findings suggest
      that common magnitude systems are more widespread among animals than previously
      believed and need not be cortically dependent in all species.

PMID- 29207265
TI  - Reduced social-information provision by immigrants and use by residents following
      dispersal.
AB  - Greater access to social information is a proposed benefit of group living [1].
      However, individuals vary in the quantity and quality of information they provide
      [2], and prior knowledge about signaller reliability is likely important when
      receivers decide how to respond [3]. While dispersal causes regular changes in
      group membership [4], no experimental work has investigated social-information
      provision and use in this context. We studied sentinel behaviour following
      immigration in a habituated population of wild dwarf mongooses (Helogale parvula)
      [5]; sentinels (raised guards) use various vocalisations to provide social
      information [5,6]. Recent immigrants acted as sentinels rarely and significantly
      less often than residents, limiting their role as social-information providers.
      Even when recent immigrants acted as social-information providers, foragers
      responded to them less than they did to residents. Several months after arrival,
      immigrants had increased sentinel contributions, and foragers no longer responded
      differently to sentinel activity by former immigrants and residents. Our results
      raise questions about the assumed social-information benefits associated with
      increased group size.

PMID- 29207266
TI  - Animal Communication: Origins of Sequential Structure in Birdsong.
AB  - Culturally transmitted behaviors have an innate foundation, but the detailed
      sequential structure of such complex, acquired behaviors is often an outcome of
      historical accidents. New research has identified innate predispositions for
      structuring vocal sequences in culturally acquired birdsong.

PMID- 29207267
TI  - Evolution: New Gene-Rich Mitochondria Found across the Eukaryotic Tree.
AB  - Mitochondria are the energy-generating organelles that power eukaryotic cells.
      Originally descended from endosymbiotic bacteria, their genomes have shrunk
      during evolution. New analyses suggest that large, gene-rich mitochondrial
      genomes are more common than previously thought, with interesting implications
      for eukaryotic genome evolution.

PMID- 29207268
TI  - Cortical Processing: How Mice Predict the Visual Effects of Locomotion.
AB  - New research identifies a frontal area in the mouse neocortex that sends
      predictions of locomotion-coupled visual flow to visual cortex. The findings
      support predictive coding theories of cortical processing.

PMID- 29207269
TI  - Actin Networks: Adapting to Load through Geometry.
AB  - Cell migration frequently involves the protrusion of lamellipodial actin
      networks, the structure and regulation of which have been studied for decades.
      New work highlights how the geometry of these networks endows cells with the
      ability to adapt to environmental conditions and load.

PMID- 29207270
TI  - Plant Development: Keeping on the Straight and Narrow and Flat.
AB  - Plant leaves have functionally specialized upper and lower sides. Two recent
      studies show that these opposite identities are derived from a pre-pattern in the
      shoot meristem and the border between them is maintained by mobile small RNAs
      with morphogen-like properties.

PMID- 29207271
TI  - Microbial Ecology: Community Coalescence Stirs Things Up.
AB  - When methane-producing microbial communities are mixed experimentally, the
      resulting community is dominated by the community with the greatest resource-use
      efficiency. These results suggest a degree of community cohesion, or the
      maintenance of that initial community in the mix.

PMID- 29207272
TI  - Evolution: Weevils Get Tough on Symbiotic Tyrosine.
AB  - Weevils, which represent one of the most diverse groups of terrestrial insects in
      nature, obtain a tough exoskeleton through the activity of an ancient bacterial
      symbiont with a tiny genome that serves as a factory for the production of
      tyrosine.

PMID- 29207273
TI  - Protein Targeting: ER Leads the Way to the Inner Nuclear Envelope.
AB  - Efficient targeting of newly synthesized membrane proteins from the endoplasmic
      reticulum to the inner nuclear membrane depends on nucleotide hydrolysis. A new
      study shows that this dependence reflects critical actions of the atlastin family
      of GTPases in maintaining the morphology of the endoplasmic reticulum network.

PMID- 29207274
TI  - Causes and Consequences of Microtubule Acetylation.
AB  - Among the different types of cytoskeletal components, microtubules arguably
      accumulate the greatest diversity of post-translational modifications (PTMs).
      Acetylation of lysine 40 (K40) of alpha-tubulin has received particular attention
      because it is the only tubulin PTM to be found in the lumen of microtubules: most
      other tubulin PTMs are found at the outer surface of the microtubule. As a
      consequence, the enzyme catalyzing K40 acetylation needs to penetrate the narrow
      microtubule lumen to find its substrate. Acetylated microtubules have been
      considered to be stable, long-lived microtubules; however, until recently, there
      was little information about whether the longevity of these microtubules is the
      cause or the consequence of acetylation. Current advances suggest that this PTM
      helps the microtubule lattice to cope with mechanical stress, thus facilitating
      microtubule self-repair. These observations now shed new light on the structural
      integrity of microtubules, as well as on the mechanisms and biological functions
      of tubulin acetylation. Here, we discuss recent insights into how acetylation is
      generated in the lumen of microtubules, and how this 'hidden' PTM can control the
      properties and functions of microtubules.

PMID- 29207275
TI  - Clinical features of otolith organ-specific vestibular dysfunction.
AB  - OBJECTIVE: To elucidate the clinical features and vestibular symptoms of patients
      with otolith organ dysfunction in the presence of normal function of the
      semicircular canals. METHODS: We reviewed the clinical records of 277 consecutive
      new patients with balance disorders who underwent testing of cervical and ocular
      vestibular evoked myogenic potentials (cVEMPs and oVEMPs) as well as caloric
      testing and video head impulse testing (vHIT). RESULTS: We identified 76 patients
      who showed normal caloric responses and normal vHIT findings in each SCC plane,
      but abnormal responses in cVEMP and/or oVEMP testing. Benign paroxysmal
      positional vertigo (BPPV) was the most common diagnosis. 37% of patients could
      not be categorized into any of the established clinical entities that could cause
      a balance disorder and did not show sensorineural hearing loss. The most common
      clinical manifestation in the idiopathic cases was recurrent rotatory vertigo
      with a duration of 1-12 h. CONCLUSIONS: The most common diagnosis of otolith
      organ-specific vestibular dysfunction was BPPV. The most common clinical
      manifestation in the idiopathic cases was recurrent rotatory vertigo.
      SIGNIFICANCE: Specific dysfunction of the otolith organs occurs in association
      with some of the undiagnosed patients with recurrent rotatory vertigo.

PMID- 29207277
TI  - Laser-captured microglia in the Alzheimer's and Parkinson's brain reveal unique
      regional expression profiles and suggest a potential role for hepatitis B in the
      Alzheimer's brain.
AB  - Expression array data from dozens of laboratories, including our own, show
      significant changes in expression of many genes in Alzheimer's disease (AD)
      patients compared with normal controls. These data typically rely on brain
      homogenates, and information about transcripts specific to microglia and other
      central nervous system (CNS) cell types, which far outnumber microglia-specific
      transcripts, is lost. We therefore used single-cell laser capture methods to
      assess the full range of microglia-specific expression changes that occur in
      different brain regions (substantia nigra and hippocampus CA1) and disease states
      (AD, Parkinson's disease, and normal controls). Two novel pathways, neuronal
      repair and viral processing were identified. Based on KEGG analysis (Kyoto
      Encyclopedia of Genes and Genomes, a collection of biological pathways), one of
      the most significant viruses was hepatitis B virus (HBV) (false discovery rate <
      0.00000001). Immunohistochemical analysis using HBV-core antibody in HBV-positive
      control, amnestic mild cognitive impairment, and HBV-positive AD cases show
      increased HBV immunoreactivity as disease pathology increases. These results are
      the first, to our knowledge, to show regional differences in human microglia. In
      addition, these data reveal new functions for microglia and suggest a novel risk
      factor for AD.

PMID- 29207278
TI  - Collision induced unfolding of isolated proteins in the gas phase: past, present,
      and future.
AB  - Rapidly characterizing the three-dimensional structures of proteins and the
      multimeric machines they form remains one of the great challenges facing modern
      biological and medical sciences. Ion mobility-mass spectrometry based techniques
      are playing an expanding role in characterizing these functional complexes,
      especially in drug discovery and development workflows. Despite this expansion,
      ion mobility-mass spectrometry faces many challenges, especially in the context
      of detecting small differences in protein tertiary structure that bear functional
      consequences. Collision induced unfolding is an ion mobility-mass spectrometry
      method that enables the rapid differentiation of subtly-different protein
      isoforms based on their unfolding patterns and stabilities. In this review, we
      summarize the modern implementation of such gas-phase unfolding experiments and
      provide an overview of recent developments in both methods and applications.

PMID- 29207276
TI  - Environmental enrichment improves hippocampal function in aged rats by enhancing
      learning and memory, LTP, and mGluR5-Homer1c activity.
AB  - Previous studies from our laboratory have shown that environmental enrichment
      (EE) in young rats results in improved learning ability and enhanced metabotropic
      glutamate receptor-dependent long-term potentiation (mGluR-dependent LTP)
      resulting from sustained activation of p70S6 kinase. Here, we investigated
      whether 1-month EE is sufficient to improve hippocampus-dependent learning and
      memory and enhance hippocampal LTP in 23-24 month-old Fischer 344 male rats. Aged
      rats were housed in environmentally enriched, socially enriched, or standard
      housing conditions. We find that aged rats exposed to 1-month of EE demonstrate
      enhanced learning and memory relative to standard housed controls when tested in
      the Morris water maze and novel object recognition behavioral tasks. Furthermore,
      we find that environmentally enriched rats perform significantly better than
      socially enriched or standard housed rats in the radial-arm water maze and
      display enhanced mGluR5-dependent hippocampal LTP. Enhanced hippocampal function
      results from activity-dependent increases in the levels of mGluR5, Homer1c, and
      phospho-p70S6 kinase. These findings demonstrate that a short exposure of EE to
      aged rats can have significant effects on hippocampal function.

PMID- 29207279
TI  - Biofabrication of morphology improved cadmium sulfide nanoparticles using
      Shewanella oneidensis bacterial cells and ionic liquid: For toxicity against
      brain cancer cell lines.
AB  - The present work determines the anticancer activity of bio-mediated synthesized
      cadmium sulfide nanoparticles using the ionic liquid and bacterial cells
      (Shewanella oneidensis). Bacterial cells have been exposed to be important
      resources that hold huge potential as ecofriendly, cost-effective, evading toxic
      of dangerous chemicals and the alternative of conventional physiochemical
      synthesis. The Shewanella oneidensis is an important kind of metal reducing
      bacterium, known as its special anaerobic respiratory and sulfate reducing
      capacity. The crystalline nature, phase purity and surface morphology of
      biosynthesized cadmium sulfide nanoparticles were analyzed by Fourier transform
      infrared spectroscopy, X-ray diffraction, Field emission scanning electron
      microscopy, Energy dispersive spectroscopy and Transmission electron microscopy.
      The use of imidazolium based ionic liquids as soft templating agent for
      controlling self-assembly and crystal growth direction of metal sulfide
      nanoparticles has also advanced as an important method. The microscopic
      techniques showed that the nanoparticles are designed on the nano form and have
      an excellent spherical morphology, due to the self-assembled mechanism of ionic
      liquid assistance. The antitumor efficiency of the cadmium sulfide nanoparticles
      was investigated against brain cancer cell lines using rat glioma cell lines. The
      effectively improved nano-crystalline and morphological structure of CdS
      nanoparticles in the presence of IL exhibit excellent cytotoxicity and dispersion
      ability on the cell shape is completely spread out showing a nice toxic
      environment against cancer cells. The cytotoxicity effect of cadmium sulfide
      nanoparticles was discussed with a diagrammatic representation.

PMID- 29207280
TI  - Hybrid capture as a tool for cervical lesions screening in HIV-infected women:
      insights from a Brazilian cohort.
AB  - INTRODUCTION: Cervical cancer remains an important burden for HIV-infected women
      in the era of combination antiretroviral therapy. Recommendations for cervical
      screening in these women diverge and may include high-risk HPV (HRHPV) testing.
      We aimed to evaluate the clinical usefulness of a single HRHPV testing for
      cervical screening of HIV-infected women. METHODS: 723 HIV-infected women from a
      Brazilian prospective cohort were included between 1996 and 2012. Inclusion
      criteria were: normal cervical cytology at baseline and having a HRHPV-test at
      baseline. We calculated incidence rates of any squamous intraepithelial lesion
      (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12
      and 36 months. Hazard Ratios were obtained using Cox proportional hazards
      regression models. RESULTS: Incidence rate for both outcomes was low (9.9 cases
      per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9
      1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95%
      CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL
      and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV
      for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months
      and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0]
      for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months). CONCLUSIONS: Incidence
      of any and high grade cytological abnormality was significantly higher among HIV
      infected women with positive-HRHPV test. A single negative-HRHPV test helped
      reassure follow-up free of cytological abnormalities through three years of
      follow-up in HIV-infected women with negative cytology.

PMID- 29207281
TI  - Dark-chilling and subsequent photo-activation modulate expression and induce
      reversible association of chloroplast lipoxygenase with thylakoid membrane in
      runner bean (Phaseolus coccineus L.).
AB  - Lipoxygenases (LOXs) are non-haem iron-containing dioxygenases that catalyse
      oxygenation of polyunsaturated fatty acids. This reaction is the first step in
      biosynthesis of oxylipins, which play important and diverse roles in stress
      response. In this study, we identified four LOX genes (PcLOXA, B, C, D) in
      chilling-sensitive runner bean (Phaseolus coccineus L.) plant and analyzed their
      expression patterns during long term dark-chilling (4  degrees C) stress and
      during day/night (21oC/4  degrees C) temperature fluctuations. Three of the four
      identified LOX genes, namely PcLOXA, PcLOXB and PcLOXD, were induced by wounding
      stress, while only the PcLOXA was induced by dark-chilling of both detached
      (wounded) leaves and whole plants. We identified PcLOXA as a chloroplast-targeted
      LOX protein and investigated its expression during chilling stress in terms of
      abundance, localization inside chloroplasts and interactions with the thylakoid
      membranes. The analysis by immunogold electron microscopy has shown that more
      than 60% of detectable PcLOXA protein was associated with thylakoids, and dark
      chilling of leaves resulted in increased amounts of this protein detected within
      grana margins of thylakoids. This effect was reversible under subsequent photo
      activation of chilled leaves. PcLOXA binding to thylakoids is not mediated by the
      posttranslational modification but rather is based on direct interactions of the
      protein with membrane lipids; the binding strength increases under dark-chilling
      conditions.

PMID- 29207282
TI  - Responses of riverbed sediment bacteria to heavy metals: Integrated evaluation
      based on bacterial density, activity and community structure under well
      controlled sequencing batch incubation conditions.
AB  - Better understanding the responses of riverbed sediment bacteria to heavy metals
      is a key for considering using riverbed sediment bacterial community as an
      indicator of river water contamination by heavy metals. For this, integrated
      evaluation based on bacterial density, activity and community structure through
      incubation experiments under well-controlled conditions is necessary to obtain
      more closely relevant findings that are difficult to achieve through field
      studies. The findings may also include those that can serve as new evidence to
      clarify contrary findings reported in previous studies. In this study, sequencing
      batch incubation experiments were performed using sediment suspensions from three
      rivers with catchment of different land covers and uses. The effects of four
      metals (Pb, Cr, Cd and Cu) were investigated by spiking them separately under
      three different concentration levels. Glucose was added once every day as the
      carbon source throughout the whole incubation lasted for 30 days. The changing
      trends of the density of general and heterotrophic bacteria showed clearly that
      the responses of sediment bacteria to Cu were obviously stronger, followed by
      that to Cd; whereas, the responses to Pb and Cr were not apparent. For incubation
      with Cu, a short-term inhibition effect appeared in the initial 3 days and was
      then followed by a long-term promotion effect reflected by obvious increases of
      bacterial density against control. In regard of bacterial activity evaluated
      based on the first-order consumption rate for glucose, a trend of decreases was
      revealed. The results of PCR-DGGE and sequence analysis of extracted 16S rDNA
      further suggested there were bacterial species that had strong tolerance against
      the metal and could grow readily to become new dominating ones. The existence of
      such bacterial species was inferred as the reason leading to the observed
      increases of bacterial density during incubation with the metal.

PMID- 29207283
TI  - Division of labor as an emergent phenomenon of social coordination: The example
      of playing doubles-pong.
AB  - In many daily situations, our behavior is coordinated with that of others. This
      study investigated this coordination in a doubles-pong task. In this task, two
      participants each controlled a paddle that could move laterally near the bottom
      of a shared computer screen. With their paddles, the players needed to block
      balls that moved down under an angle. In doing so, they needed to make sure that
      their paddles did not collide. A successful interception led to the ball bouncing
      back upwards. Importantly, all communication other than through vision of the
      shared screen was excluded. In the experiment, the initial position of the paddle
      of the right player was varied across trials. This allowed testing hypotheses
      regarding the use of a tacitly understood boundary to divide interception space.
      This boundary could be halfway the screen, or in the middle between the initial
      positions of the two paddles. These two hypotheses did not hold. As an
      alternative to planned division of labor, the behavioral patterns might emerge
      from continuous visual couplings of paddles and ball. This was tested with an
      action-based decision model that considered the rates of change of each player's
      angle between the interception axis and the line connecting the ball and inner
      edge of the paddle. The model accounted for the observed patterns of behavior to
      a very large extent. This led to the conclusion that decisions of who would take
      the ball emerged from ongoing social coordination. Implications for social
      coordination in general are discussed.

PMID- 29207284
TI  - Correspondence to the Editor Re: Artisanal and small-scale gold mining impacts in
      Madre de Dios, Peru: Management and mitigation strategies.

PMID- 29207285
TI  - Heat and health in Antwerp under climate change: Projected impacts and
      implications for prevention.
AB  - BACKGROUND: Excessive summer heat is a serious environmental health problem in
      several European cities. Heat-related mortality and morbidity is likely to
      increase under climate change scenarios without adequate prevention based on
      locally relevant evidence. METHODS: We modelled the urban climate of Antwerp for
      the summer season during the period 1986-2015, and projected summer daily
      temperatures for two periods, one in the near (2026-2045) and one in the far
      future (2081-2100), under the Representative Concentration Pathway (RCP) 8.5. We
      then analysed the relationship between temperature and mortality, as well as with
      hospital admissions for the period 2009-2013, and estimated the projected
      mortality in the near future and far future periods under changing climate and
      population, assuming alternatively no acclimatization and acclimatization based
      on a constant threshold percentile temperature. RESULTS: During the sample period
      2009-2013 we observed an increase in daily mortality from a maximum daily
      temperature of 26 degrees C, or the 89th percentile of the maximum daily
      temperature series. The annual average heat-related mortality in this period was
      13.4 persons (95% CI: 3.8-23.4). No effect of heat was observed in the case of
      hospital admissions due to cardiorespiratory causes. Under a no acclimatization
      scenario, annual average heat-related mortality is multiplied by a factor of 1.7
      in the near future (24.1deaths/year CI 95%: 6.78-41.94) and by a factor of 4.5 in
      the far future (60.38deaths/year CI 95%: 17.00-105.11). Under a heat
      acclimatization scenario, mortality does not increase significantly in the near
      or in the far future. CONCLUSION: These results highlight the importance of a
      long-term perspective in the public health prevention of heat exposure,
      particularly in the context of a changing climate, and the calibration of
      existing prevention activities in light of locally relevant evidence.

PMID- 29207286
TI  - Short-term effects of ultrafine particles on daily mortality by primary vehicle
      exhaust versus secondary origin in three Spanish cities.
AB  - BACKGROUND: Evidence on the short-term effects of ultrafine particles (with
      diameter<100nm, UFP) on health is still inconsistent. New particles in ambient
      urban air are the result of direct emissions and also the formation of secondary
      UFP from gaseous precursors. We segregated UFP into these two components and
      investigated their impact on daily mortality in three Spanish cities affected by
      different sources of air pollution. METHODS: We separated the UFP using a method
      based on the high correlation between black carbon (BC) and particle number
      concentration (N). The first component accounts for aerosol constituents emitted
      by vehicle exhaust (N1) and the second for the photochemical new particle
      formation enhancements (N2). We applied city-specific Poisson regression models,
      adjusting for long-term trends, temperature and population dynamics. RESULTS:
      Mean BC levels were higher in Barcelona and Tenerife (1.8 and 1.2MUg.m-3,
      respectively) than in Huelva (0.8MUg.m-3). While mean UFP concentrations were
      similar in the three cities, from which N1 was 40% in Barcelona, 46% in Santa
      Cruz de Tenerife, and 27% in Huelva. We observed an association with N1 and daily
      mortality in Barcelona, by increasing approximately 1.5% between lags 0 and 2,
      per an interquartile increase (IQR) of 3277cm-3, but not with N2. A similar
      pattern was found in Santa Cruz de Tenerife, although none of the associations
      were significant. Conversely, in the industrial city of Huelva mortality was
      associated with N2 at lag 0, by increasing 3.9% per an IQR of 12,032.cm-3.
      CONCLUSION: The pattern and origin of UFP determines their short-term effect on
      human health. BC is possibly the better parameter to evaluate the health effects
      of particulate vehicle exhaust emissions, although in areas influenced by
      domestic solid fuel combustion this should also be taken into account.

PMID- 29207287
TI  - Nursing students' experiences with refugees with mental health problems in
      Jordan: A qualitative content analysis.
AB  - OBJECTIVES: The aim of this study was to describe Jordanian nursing students'
      experience of caring for refugees with mental health problems. BACKGROUND:
      According to refugees' experiences of crisis, a well-educated staff is needed to
      provide high quality of care due to mental health problems. Therefore, health
      professionals play an important role in creating an environment that promotes
      human rights regardless of ethnic origin. SETTINGS, PARTICIPANTS, METHOD: The
      study comprised eight interviews and was analysed using content analysis, a
      qualitative method that involves an inductive approach, to increase our
      understanding of nursing students' perspective and thoughts regarding caring for
      refugees with mental health problems. RESULTS: The results formed one category:
      to be challenged by refugees' mental health issues and three subcategories:
      managing refugees' mental health needs, affected by refugees' mental health, and
      improve mental healthcare for refugees. CONCLUSION: Language problems could be
      managed by using interpreters to decrease cultural clashes to facilitate equal
      healthcare. In addition, well-educated (theoretical knowledge) and trained
      (practical knowledge) nursing students have potential to fulfil refugees' care
      needs regardless of ethnicity or background by using nursing interventions built
      on communication skills and cultural competences (theory, practice) to facilitate
      high quality of healthcare.

PMID- 29207288
TI  - Adaptation and pretesting of the College Persistence Questionnaire V3 (Short
      Form) for measuring intention to persist among Aboriginal Diploma of Nursing
      students.
AB  - BACKGROUND: Culturally appropriate health care delivery is essential to improve
      health outcomes for Aboriginal peoples. There is a shortage of Aboriginal and
      Torres Strait Islander nurses partly due to disproportionately high non
      completion rates among tertiary sector students. The College Persistence
      Questionnaire V3 (Short Form) provides scales for gauging major predictors of
      retention. OBJECTIVE: To adapt an instrument for measuring intention to persist
      among Aboriginal Diploma of Nursing students. DESIGN: Instrument adaptation and
      pretesting. PARTICIPANTS: A convenience sample of Aboriginal Diploma of Nursing
      students (N=21) at a registered training organisation in Australia. METHODS: The
      instrument was mapped against the domain of interest and modified. Ten experts
      reviewed its content validity; its reading ease and educational grade reading
      level were assessed. RESULTS: The expert panel endorsed individual items as valid
      (item-level Content Validity Index 0.90-1.00) and scale-level validation was
      acceptable (average scale-level Content Validity Index=0.98). The minimally
      adapted instrument was 'fairly easy' to read and suitable for general adult
      audiences (Flesch Reading Ease score 71.3) and was below the United States 8th
      grade reading level (Flesch-Kincaid Grade Level 6.7). Students took <30min to
      complete the questionnaire. All understood its purpose, found instructions clear,
      and questions easy to answer. Most rated its length 'Just right'. CONCLUSION: The
      College Persistence Questionnaire - Registered Training Organisation Version
      appears suitable for assessing factors influencing retention/attrition among
      Aboriginal Diploma of Nursing students. Piloting and psychometric evaluation is
      recommended.

PMID- 29207289
TI  - Accuracy evaluation of a method to partition ground reaction force and center of
      pressure in cane-assisted gait using an instrumented cane with a triaxial force
      sensor.
AB  - Clarifying the biomechanics of cane-assisted gait in elderly individuals and
      patients with gait disorders is important for developing better therapeutic
      interventions in the fields of rehabilitation and orthopedics. However, if the
      foot and the cane in the ipsilateral hand are placed on the same force plate
      simultaneously, the force plate cannot separate the forces as it records the sum
      of the forces. To overcome this indeterminacy problem of the ground reaction
      force (GRF) and the center of pressure (COP) in cane-assisted gait analysis, a
      method to partition the GRF and COP using an instrumented cane with a force
      transducer has been proposed. However, the accuracy and precision of the
      estimated GRF and COP has not been evaluated previously. We therefore
      reestablished a framework to partition the foot and cane forces during walking
      using an instrumented cane with a triaxial force sensor and evaluated the
      accuracy and precision of the method using a force plate array. Cane-assisted
      gait of healthy adults and hemiplegic patients were measured. Mean accuracy and
      precision associated with the GRF and COP measurements were approximately 0.4+/
      1.4N and 0.2+/-2.7mm, respectively, indicating that the separations of the GRF
      and COP were sufficiently accurate for kinetic gait analysis. Although some
      methodological limitations certainly apply, this system will serve as a useful
      tool for improved therapeutic interventions.

PMID- 29207290
TI  - Physiological-phased kinetic characteristics of microalgae Chlorella vulgaris
      growth and lipid synthesis considering synergistic effects of light, carbon and
      nutrients.
AB  - To comprehensively understand kinetic characteristics of microalgae growth and
      lipid synthesis in different phases, a phase-feeding strategy was proposed to
      simultaneously regulate light, carbon and nutrients in adaption, growth and
      stationary phases of microalgae cultivation. Physiological-phased kinetic
      characteristics of microalgae Chlorella vulgaris growth and lipid synthesis under
      synergistic effects of light, carbon and nutrients were investigated, and supply
      demand relationships of electrons and energy between light and dark reactions of
      photosynthesis process were discussed. Finally, the optimized cultivation
      strategy for microalgae in various phases were obtained, under which the lipid
      productivity was significantly improved from 130.11 mg/L/d to 163.42 mg/L/d. The
      study provided some important guidance for the large-scale production of biofuels
      from microalgae.

PMID- 29207291
TI  - Transcriptome analysis of ovine granulosa cells reveals differences between small
      antral follicles collected during the follicular and luteal phases.
AB  - Ovarian follicular growth occurs in both the follicular and luteal phases of the
      estrous cycle but in very different endocrine contexts. In both phases, many
      small antral follicles with similar morphologic and histologic characteristics
      are present within the ovaries as a reserve for the terminal folliculogenesis.
      However, there are several gaps in our molecular knowledge of the gene expression
      profiles of small antral follicles in the follicular and luteal phases. The aim
      of the present study was to use RNA sequencing to compare and analyze the global
      transcriptional profile of ovine granulosa cells collected from small antral
      follicles (1-3 mm) either during the follicular or the luteal phase of the
      estrous cycle, with the hypothesis that they should be differential. We
      identified 663 genes whose mRNA was differentially expressed or accumulated in
      the granulosa cell layer of small antral follicles in the two phases. A
      comprehensive interpretation of these data was performed through integrative
      analyses (Gene Ontology, Ingenuity Pathway Analysis) and the exploitation of
      already available transcriptomic data on follicular growth and atresia. In
      particular, we observed that the contrasted endocrine context between follicular
      and luteal phases may have an impact on estradiol, follicle-stimulating hormone
      (FSH), and on the activin/inhibin signaling pathways. Furthermore, we reveal the
      possible initiation of early follicular atresia in small antral follicles during
      the follicular phase in interaction with the presence of immune cells. This study
      provides new insights into the gene expression profile in ovine granulosa cells,
      and we suggest that these molecular changes may have an implication at the time
      of follicle selection.

PMID- 29207292
TI  - Reproductive system development in male and female horse embryos and fetuses:
      Gonadal hyperplasia revisited.
AB  - In horses, pregnancy is characterized by high levels of maternal estrogens that
      are produced largely by the interstitial tissue inside the gonads of the
      offspring, associated with a physiological gonadal hyperplasia, that is uncommon
      in other species. However, a detailed structural-functional understanding of the
      early stages of gonadal development and hyperplasia has remained elusive in horse
      pregnancy because of the lack of substantial data. The goal of this study was to
      describe the genital organs' development in 19 early horse embryos and fetuses
      (days 20-140 of gestation) of both sexes by means of anatomy, histology,
      stereology, and immunohistochemistry, with a specific focus on gonadal
      hyperplasia and interstitial tissue development. Gonadal hyperplasia with similar
      amounts of interstitial cells was observed in both sexes, but only during the
      early stage of development (days 40-90). Surprisingly, a higher degree of
      hyperplasia, characterized by larger amounts of interstitial cell-rich areas, was
      seen in fetal ovaries from 90 days of gestation onwards. Another novel aspect was
      that parallel to the hyperplasia of the interstitial cells, a much more
      precocious and pronounced differentiation of germinal cells was seen in the
      ovary, characterized by an earlier peak and decrease of DAZL and OCT protein
      immune markers. In conclusion, a reduced degree of hyperplasia and interstitial
      tissue in the fetal testis after 90 days of gestation suggests the existence of a
      more efficient mechanism regarding the synthesis of estrogen precursors as a
      structural or physiological difference between both fetal sexes, which warrants
      further investigation.

PMID- 29207293
TI  - Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of
      in vitro derived bovine embryos.
AB  - The aim of this work was to evaluate whether the treatment with the pan-caspase
      inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) during
      cryopreservation and post-warming in vitro culture improves cryotolerance of
      bovine in vitro produced (IVP) embryos. Abattoir derived bovine oocytes were in
      vitro matured, fertilized and cultured according to standard procedure. On Day 7,
      embryo yields were assessed and blastocysts randomly divided in 2 groups:
      vitrification and post-warming culture in the absence (n = 184) or presence (n =
      156) of 20 MUM Z-VAD-FMK. Resistance to cryopreservation was evaluated post
      warming culture by assessing the survival rate and hatching rate. Differential
      staining combined with in situ terminal deoxynucleotidyl transferase mediated
      dUTP nick end labelling (TUNEL) technique was performed to evaluate total cells
      number, cell allocation into inner cell mass (ICM) and trophectoderm (TE)
      lineages, as well as the DNA fragmentation rate of vitrified blastocysts, while
      immunohystochemical staining was used to assess the level of cleaved-caspase 3.
      It was demonstrated that inhibition of caspase activity by Z-VAD-FMK increases
      embryo cryotolerance, as indicated by higher survival (76.1 vs 51.1%; P < 0.01)
      and hatching rates (26.5 vs 17.6%; P < 0.05) after 48 h of post-warming culture.
      Furthermore, Z-VAD-FMK decreased both the average number (4.7 +/- 0.3 vs 7.7 +/-
      0.5; P < 0.01) and the percentage (3.4 +/- 0.2 vs 6.1 +/- 0.5; P < 0.01) of DNA
      fragmented cells in blastocysts compared to the control. No differences were
      recorded in the average number of ICM, TE and total cells between groups. The
      level of cleaved-caspase-3, the downstream effector of apoptosis, and its
      relative percentage on total area of blastocysts was reduced (P < 0.01) in the
      presence of Z-VAD-FMK both at thawing (1.29 +/- 0.17 vs 3.24 +/- 0.46) and after
      48 h post-warming culture (1.46 +/- 0.17 vs 5.06 +/- 0.41). In conclusion, the
      addition of 20 MUM Z-VAD-FMK during vitrification/warming and post-warming
      culture partially inhibits cryopreservation-induced apoptosis by reducing the
      level of active caspase 3, suggesting a potential use as an additive to
      ameliorate the efficiency of embryo cryopreservation in cattle, critical for a
      further diffusion of IVEP technology in the field. Further studies are though
      needed to evaluate the effect of Z-VAD-FMK on post-transfer embryo development
      before considering a commercial application.

PMID- 29207294
TI  - Placental structure and function in different breeds in horses.
AB  - Ponies and sometimes draft horses are often used as experimental models for
      horses although size and metabolic parameters are known to vary between horse
      breeds. So far, there is little information about differences of placental
      structure and no information about differences of placental function between
      breeds. The aim of this study was to investigate differences in placental size,
      structure and function at birth in relation to foal size and weight in ponies,
      Saddlebred and draft horses. Pony, Saddlebred and draft horse pregnancies were
      obtained by artificial insemination over 2 successive breeding seasons. Foals and
      total fetal membranes (TFM) were weighed and placentas measured for surface area
      at term. Placentas were sampled above the umbilical cord insertion. Surface
      density and volume fraction of the different cellular components of the placenta
      were measured on histological sections using stereology. The expression of genes
      involved in growth and development, nutrient transfer and vascularization was
      compared between groups. Foals and TFM were lighter at birth in ponies than
      Saddlebred horses, and both were lighter compared to draft horses. The surface
      density and volume fraction of microcotyledonary vessels was increased in pony
      compared to Saddlebred placentas. The relative expression of genes involved in
      growth and development was different between breeds and increased with maternal,
      fetal and placental weight. Primiparous dams produced lighter foals and smaller
      placentas, associated with a decreased volume fraction of microcotyledonary
      vessels and genes involved in growth and development and vascularization. Foal
      sex had little effect on placental structure and function as the expression of
      only one gene differed according to sex, with EGFR expression being decreased in
      placentas of females compared to males. In conclusion, foal and placental weight,
      as well as placental expression of genes involved in growth and development were
      correlated with maternal size. Placental structure also differed between breeds,
      with a stronger difference between ponies and both breeds of horses.

PMID- 29207295
TI  - Effects of dietary omega-3 and -6 supplementations on phospholipid fatty acid
      composition in mice uterus during window of pre-implantation.
AB  - Since fatty acid composition of uterus phospholipids is likely to influence
      embryo implantation, this study was conducted to investigate the effects of
      dietary omega-3 and -6 fatty acids on implantation rate as well as uterine
      phospholipid fatty acids composition during mice pre-implantation period. Sixty
      female mice were randomly distributed into:1) control (standard pellet), 2) omega
      3 (standard pellet + 10% w/w of omega-3 fatty acids) and 3) omega-6 (standard
      pellet + 10% w/w of omega-6 fatty acids). Uterine phospholipid fatty acid
      composition during the pre-implantation window (days 1-5 of pregnancy) was
      analyzed using gas-chromatography. The implantation rate on the fifth day of
      pregnancy was also determined. Our results showed that on days 1, 2 and 3 of
      pregnancy, the levels of arachidonic acid (ARA) as well as total omega-6 fatty
      acids were significantly higher and the levels of linolenic acid and total omega
      3 fatty acids were statistically lower in the omega-6 group compared to the omega
      3 group (p < 0.05). On the fourth day of pregnancy, only the ARA, total omega-6
      fatty acids, and poly-unsaturated fatty acids levels were significantly different
      between the two dietary supplemented groups (p < 0.05). There were positive
      correlations between the levels of omega-6 fatty acids, especially ARA, with the
      implantation rate. The present study showed that diets rich in omega-3 and -6
      fatty acids could differently modify uterine phospholipid fatty acid composition
      and uterine levels of phospholipid ARA, and that the total omega-6 fatty acids
      had a positive association with the implantation rate.

PMID- 29207296
TI  - Microplastics in freshwater river sediments in Shanghai, China: A case study of
      risk assessment in mega-cities.
AB  - Microplastics, which are plastic debris with a particle diameter of less than 5
      mm, have attracted growing attention in recent years. Its widespread
      distributions in a variety of habitats have urged scientists to understand deeper
      regarding their potential impact on the marine living resources. Most studies on
      microplastics hitherto are focused on the marine environment, and research on
      risk assessment methodology is still limited. To understand the distribution of
      microplastics in urban rivers, this study investigated river sediments in
      Shanghai, the largest urban area in China. Seven sites were sampled to ensure
      maximum coverage of the city's central districts, and a tidal flat was also
      included to compare with river samples. Density separation, microscopic
      inspection and MU-FT-IR analysis were conducted to analyze the characteristics of
      microplastics and the type of polymers. The average abundance of microplastics in
      six river sediment samples was 802 items per kilogram of dry weight. The
      abundance in rivers was one to two orders of magnitude higher than in the tidal
      flat. White microplastic spheres were most commonly distributed in river
      sediments. Seven types of microplastics were identified, of which polypropylene
      was the most prevailing polymers presented. The study then conducted risk
      assessment of microplastics in sediments based on the observed results, and
      proposed a framework of environmental risk assessment. After reviewing waste
      disposal related legislation and regulations in China, this study conclude that
      in situ data and legitimate estimations should be incorporated as part of the
      practice when developing environmental policies aiming to tackle microplastic
      pollution.

PMID- 29207297
TI  - Differences between a deciduous and a conifer tree species in gaseous and
      particulate emissions from biomass burning.
AB  - In the Mediterranean ecosystem, wildfires are very frequent and the predicted
      future with a probable increase of fires could drastically modify the vegetation
      scenarios. Vegetation fires are an important source of gases and primary
      emissions of fine carbonaceous particles in the atmosphere. In this paper, we
      present gaseous and particulate emissions data from the combustion of different
      plant tissues (needles/leaves, branches and needle/leaf litter), obtained from
      one conifer (Pinus halepensis) and one deciduous broadleaf tree (Quercus
      pubescens). Both species are commonly found throughout the Mediterranean area,
      often subject to wildfires. Experiments were carried out in a combustion chamber
      continuously sampling emissions throughout the different phases of a fire (pre
      ignition, flaming and smoldering). We identified and quantified 83 volatile
      organic compounds including important carcinogens that can affect human health.
      CO and CO2 were the main gaseous species emitted, benzene and toluene were the
      dominant aromatic hydrocarbons, methyl-vinyl-ketone and methyl-ethyl-ketone were
      the most abundant measured oxygenated volatile organic compounds. CO2 and methane
      emissions peaked during the flaming phase, while the peak of CO emissions
      occurred during the smoldering phase. Overall, needle/leaf combustion released a
      greater amount of volatile organic compounds into the atmosphere than the
      combustion of branches and litter. There were few differences between emissions
      from the combustion of the two tree species, except for some compounds. The
      combustion of P. halepensis released a great amount of monoterpenes as alpha
      pinene, beta-pinene, p-cymene, sabinene, 3-carene, terpinolene and camphene that
      are not emitted from the combustion of Q. pubescens. The combustion of branches
      showed the longest duration of flaming and peak of temperature. Data presented
      appear crucial for modeling with the intent of understanding the loss of C during
      different phases of fire and how different typologies of biomass can affect
      wildfires and their speciation emissions profile.

PMID- 29207298
TI  - Effects of biochar on hydraulic conductivity of compacted kaolin clay.
AB  - Compacted clay is widely used as capillary barriers in landfill final cover
      system. Recently, biochar amended clay (BAC) has been proposed as a sustainable
      alternative cover material. However, the effects of biochar on saturated
      hydraulic conductivity (ksat) of clay with high degree of compaction is not yet
      understood. The present study aims to investigate the effects of biochar on ksat
      of compacted kaolin clay. Soil specimens were prepared by amending kaolin clay
      with biochar derived from peanut-shell at 0, 5 and 20% (w/w). The ksat of soil
      specimens was measured using a flexible water permeameter. The effects of biochar
      on the microstructure of the compacted clay was also investigated using MIP.
      Adding 5% and 20% of biochar increased the ksat of compacted kaolin clay from 1.2
      * 10-9 to 2.1 * 10-9 and 1.3 * 10-8 ms-1, respectively. The increase in ksat of
      clay was due to the shift in pore size distribution of compacted biochar-amended
      clay (BAC). MIP results revealed that adding 20% of biochar shifted the dominant
      pore diameter of clay from 0.01-0.1 MUm (meso- and macropores) to 0.1-4 MUm
      (macropores). Results reported in this communication revealed that biochar
      application increased the ksat of compacted clay, and the increment was
      positively correlated to the biochar percentage.

PMID- 29207299
TI  - A novel screening method to identify air pollution by genotoxic compounds.
AB  - Genotoxic compounds, as common contaminants of the air environment, are of
      interest in air pollution monitoring. There are several methods to determine the
      level of these contaminants in different localities, many of which may be
      difficult to access with the use of conventional active and passive samplers. In
      the present study, the needles Pinus mugo Turra and Picea abies were used to
      monitor sampling localities in Austria, Slovakia, and the Czech Republic. Needles
      were extracted and chemical analysis and the genotoxicity bioassay SOS chromotest
      were used to obtain complex information about the chemical mixture of pollutants
      present and their genotoxic effects. The SOS chromotest method was optimized by
      using a CPRG chromogenic substrate to reduce the false positive genotoxic effect
      of needle extracts. Pinus mugo Turra and Picea abies were identified as suitable
      passive sampling matrices for long-term air monitoring using the same plants
      sampled at the same time. The presented study brings an innovative method for the
      fast screening and identification of localities loaded by genotoxic active air
      contaminants.

PMID- 29207300
TI  - Evaluating the relationship between temporal changes in land use and resulting
      water quality.
AB  - Changes in land use have a direct impact on receiving water quality. Effective
      mitigation strategies require the accurate prediction of water quality in order
      to enhance community well-being and ecosystem health. The research study employed
      Bayesian Network modelling to investigate the validity of using cross-sectional
      and longitudinal data on water quality and land use for predicting water quality
      in a mixed use catchment and the role it plays in the generation of blue-green
      algae in the receiving marine environment. Bayesian Network modelling showed that
      cross-sectional and longitudinal data analyses generate contrasting information
      about the influence of different land uses on surface water pollution. The
      modelling outcomes highlighted the lack of reliability in cross-sectional data
      analysis, based on the indication of spurious relationships between water quality
      and land use. On the other hand, the longitudinal data analysis, which accounted
      for changes in water quality and land use over a ten-year period, informed how
      catchment water quality varies in response to temporal changes in land use. The
      longitudinal data analysis further revealed that the types of anthropogenic
      activities have a more significant influence on pollutant generation than the
      change in the area extent of different land uses over time. Therefore, the
      careful interpretation of the findings derived solely from cross-sectional data
      analysis is important in the design of long-term strategies for pollution
      mitigation.

PMID- 29207301
TI  - Percutaneous low-dose CT-guided lung biopsy with an augmented reality navigation
      system: validation of the technique on 496 suspected lesions.
AB  - PURPOSE: To validate a CT-navigation system during percutaneous lung biopsy
      (PLB). METHODS: Four hundred-ninety-six patients underwent low-dose CT-guided
      PLB. Lesion diameter (LD), procedural time (PT), histologic validity, lesion
      distance from pleural surface (DPS), needle distance travelled during procedure
      (DTP), complications and radiation exposure were recorded. RESULTS: Hysto
      patological diagnosis was obtained in 96.2% cases. Mean PT, DPS, DTP, LD were
      respectively 29.5min, 12.4mm, 17.9mm, 20.7mm. In cases of major complications
      (4.6%), higher values of DTP were measured. CONCLUSIONS: CT-navigation system
      allowed a good success in terms of diagnosis in small lesions and when a long DTP
      is required.

PMID- 29207302
TI  - Lactic acid fermentation of human excreta for agricultural application.
AB  - Studies show that source separated human excreta have a fertilizing potential
      with benefits to plant growth and crop yield similar or exceeding that of mineral
      fertilizers. The main challenges in fertilizing with excreta are pathogens, and
      an increased risk of eutrophication of water bodies in case of runoff. This
      review shows that lactic acid fermentation of excreta reduces the amount of
      pathogens, minimizes the nutrient loss and inhibits the production of malodorous
      compounds, thus increasing its agricultural value. Pathogens (e.g.,
      Enterobacteriacea, Staphylococcus and Clostridium) can be reduced by 7 log CFUg-1
      during 7-10 days of fermentation. However, more resistant pathogens (e.g.
      Ascaris) are not always efficiently removed. Direct application of lacto
      fermented faeces to agriculture may be constrained by incomplete decomposition,
      high concentrations of organic acids or insufficient hygienization. Post
      treatment by adding biochar, vermi-composting, or thermophilic composting
      stabilizes and sanitizes the material. Pot and field experiments on soil
      conditioners obtained via lactic acid fermentation and post treatment steps
      (composting or biochar addition) demonstrated increased crop yield and growth, as
      well as improved soil quality, in comparison to unfertilized controls.

PMID- 29207303
TI  - The fate of cyanuric acid in biological wastewater treatment system and its
      impact on biological nutrient removal.
AB  - Cyanuric acid (CA) is widely used in living and production. It is a kind of
      environmental priority pollutants which exists chronically in soil and water, but
      is difficult to be chemically hydrolyzed or oxidized. The behavior of CA at
      different levels of 0, 0.01, 0.10 and 1.00 mg L-1 in biological wastewater
      treatment process was investigated in this paper. Experimental results showed
      that CA (0.01 and 0.10 mg L-1) was removed in biological wastewater treatment
      process, which was mainly achieved by biodegradation of particular species
      (Acidovorax and Pseudomonas) in the anaerobic condition. However, 1.00 mg L-1 CA
      was reluctant to be degraded in biological wastewater treatment system. With the
      CA level increase from 0 to 1.00 mg L-1, total nitrogen removal efficiency
      decreased from 97.23 to 74.72%. The presence of CA promoted both the synthesis
      and decomposition metabolisms of poly-hydroxyalkanoates and glycogen, thereby
      providing the advantage for phosphorus removal. CA could inhibit nitrification
      process because of inhibition to nitrite oxidizing bacteria (NOB). Moreover, the
      microbial community of activated sludge was changed by the exposure of CA.
      Polyphosphate accumulating organisms, such as Bacteroidetes, Chloroflexi and
      Saccharibacteria increased, but the abundance of Nitrospirae was decreased.

PMID- 29207304
TI  - Evaluating statistical model performance in water quality prediction.
AB  - Exposure to contaminated water while swimming or boating or participating in
      other recreational activities can cause gastrointestinal and respiratory disease.
      It is not uncommon for water bodies to experience rapid fluctuations in water
      quality, and it is therefore vital to be able to predict them accurately and in
      time so as to minimise population's exposure to pathogenic organisms. E. coli is
      commonly used as an indicator to measure water quality in freshwater, and higher
      counts of E. coli are associated with increased risk to illness. In this case
      study, we compare the performance of a wide range of statistical models in
      prediction of water quality via E. coli levels for the weekly data collected over
      the summer months from 2006 to 2014 at the recreational site on the Oreti river
      in Wallacetown, New Zealand. The models include naive model, multiple linear
      regression, dynamic regression, regression tree, Markov chain, classification
      tree, random forests, multinomial logistic regression, discriminant analysis and
      Bayesian network. The results show that Bayesian network was superior to all the
      other models. Overall, it had a leave-one-out and k-fold cross validation error
      rate of 21%, while predicting the majority of instances of E. coli levels
      classified as unsafe by the Microbiological Water Quality Guidelines for Marine
      and Freshwater Recreational Areas 2003, New Zealand. Because Bayesian networks
      are also flexible in handling missing data and outliers and allow for continuous
      updating in real time, we have found them to be a promising tool, and in the
      future, plan to extend the analysis beyond the current case study site.

PMID- 29207305
TI  - Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse
      blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies.
AB  - Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer
      cells to radiation and chemotherapeutic agents. However, the optimal delivery
      method, dose, and tumor concentrations required for these effects are not known.
      This is in part due to a lack of sensitive and reproducible analytical methods
      for HCQ quantitation in small animals. As such, we developed and validated a
      selective and sensitive liquid chromatography coupled with tandem mass
      spectrometry (LC-MS/MS) method for simultaneous quantitation of
      hydroxychloroquine and its metabolites in mouse blood and tissues. The
      chromatographic separation and detection of analytes were achieved on a reversed
      phase Thermo Aquasil C18 (50*4.6mm, 3MU) column, with gradient elution using 0.2%
      formic acid and 0.1% formic acid in methanol as mobile phase at a flow rate of
      0.5mL/min. Simple protein precipitation was utilized for extraction of analytes
      from the desired matrix. Analytes were separated and quantitated using MS/MS with
      an electrospray ionization source in positive multiple reaction monitoring (MRM)
      mode. The MS/MS response was linear over the concentration range from 1 to
      2000ng/mL for all analytes with a correlation coefficient (R2) of 0.998 or
      better. The within- and between-day precision (relative standard deviation, %
      RSD) and accuracy were within the acceptable limits per FDA guidelines. The
      validated method was successfully applied to a preclinical pharmacokinetic mouse
      study involving low volume blood and tissue samples for hydroxychloroquine and
      metabolites.

PMID- 29207306
TI  - Membrane bending by actin polymerization.
AB  - Actin polymerization provides driving force to aid several types of processes
      that involve pulling the plasma membrane into the cell, including phagocytosis,
      cellular entry of large viruses, and endocytosis. In endocytosis, actin
      polymerization is especially important under conditions of high membrane tension
      or high turgor pressure. Recent modeling efforts have shown how actin
      polymerization can give rise to a distribution of forces around the endocytic
      site, and explored how these forces affect the shape dynamics; experiments have
      revealed the structure of the endocytic machinery in increasing detail, and
      demonstrated key feedback interactions between actin assembly and membrane
      curvature. Here we provide a perspective on these findings and suggest avenues
      for future research.

PMID- 29207307
TI  - Systemic sclerosis: Clinical manifestations, anesthetic and orthopedic
      considerations in a patient.
AB  - INTRODUCTION: Systemic sclerosis is a rare and progressive multisystem autoimmune
      disorder that is characterized pathologically by vascular abnormalities,
      connective tissue sclerosis and atrophy of skin and various internal organs
      (e.g., alimentary tract, lungs, heart, kidney, CNS), and autoantibodies. With an
      unknown etiology, Scleroderma is a complex polygenetic disease. A recent Genome
      Wide Association Study (GWAS) confirmed a strong association with the Major
      Histocompatibility Complex (MHC) and autoimmunity. We provide a case scenario
      along with a review of the systems involved and challenges physicians can face in
      dealing with this rare disease. CASE PRESENTATION: Our patient, a known case of
      systemic sclerosis, was admitted with a history of right femur fracture following
      a fall. We highlight the medical, anesthetic and surgical challenges faced by our
      team in the management of this patient. We will explain the stages patient faced
      in treatment process till her death. We combined the case report with detailed
      literature review of this rare disease. DISCUSSION: Systemic sclerosis is a
      complex disease process with many different levels of system involvement. Patient
      needs to be reviewed thoroughly in preoperative period by multidisciplinary team
      and counseled in detail about the difficulties in procedure, risks and
      complications. CONCLUSION: Patient with scleroderma presents a challenge to the
      surgical team and anesthetist and a multidisciplinary approach should be followed
      with all of these patients to avoid catastrophic results.

PMID- 29207308
TI  - Road MAPs to engineer host microbiomes.
AB  - Microbiomes contribute directly or indirectly to host health and fitness. Thus
      far, investigations into these emergent traits, referred to here as microbiome
      associated phenotypes (MAPs), have been primarily qualitative and taxonomy-driven
      rather than quantitative and trait-based. We present the MAPs-first approach, a
      theoretical and experimental roadmap that involves quantitative profiling of MAPs
      across genetically variable hosts and subsequent identification of the underlying
      mechanisms. We outline strategies for developing 'modular microbiomes'-synthetic
      microbial consortia that are engineered in concert with the host genotype to
      confer different but mutually compatible MAPs to a single host or host
      population. By integrating host and microbial traits, these strategies will
      facilitate targeted engineering of microbiomes to the benefit of agriculture,
      human/animal health and biotechnology.

PMID- 29207309
TI  - Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal
      activity and show significant inhibition of parasite acetylcholinesterases.
AB  - Over 4.5 billion people are at risk of infection with soil transmitted helminths
      and there are concerns about the development of resistance to the handful of
      frontline nematocides in endemic populations. We investigated the anti-nematode
      efficacy of a series of polypyridylruthenium(II) complexes and showed they were
      active against L3 and adult stages of Trichuris muris, the rodent homologue of
      the causative agent of human trichuriasis, T. trichiura. One of the compounds,
      Rubb12-mono, which was among the most potent in its ability to kill L3 (IC50 =
      3.1 +/- 0.4 MUM) and adult (IC50 = 5.2 +/- 0.3 MUM) stage worms was assessed for
      efficacy in a mouse model of trichuriasis by administering 3 consecutive daily
      oral doses of the drug 3 weeks post infection with the murine whipworm Trichuris
      muris. Mice treated with Rubb12-mono showed an average 66% reduction (P = 0.015)
      in faecal egg count over two independent trials. The drugs partially exerted
      their activity through inhibition of acetylcholinesterases, as worms treated in
      vitro and in vivo showed significant decreases in the activity of this class of
      enzymes. Our data show that ruthenium complexes are effective against T. muris, a
      model gastro-intestinal nematode and soil-transmitted helminth. Further,
      knowledge of the target of ruthenium drugs can facilitate modification of current
      compounds to identify analogues which are even more effective and selective
      against Trichuris and other helminths of human and veterinary importance.

PMID- 29207311
TI  - Analysis of passenger-car crash injury severity in different work zone
      configurations.
AB  - Work zone safety remains a priority to the Federal Highway Administration, State
      Highway Departments, highway engineers, and the traveling public. Work zones
      create a hospitable environment for crashes; an issue that gained tremendous
      share of attention in recent years. Therefore, every effort should be sought out
      to reduce the injury severity of crashes in work zones. In this paper we attempt
      to investigate factors contributing to the injury severity of passenger-car
      crashes in different work zone configurations. Considering the discrete ordinal
      nature of injury severity categories, a Mixed Generalized Ordered Response Probit
      (MGORP) modeling framework was developed. The model estimation was undertaken by
      compiling a database consisting of 10 years of crashes that involved at least one
      passenger car, and occurred in a work zone. Revealing the underlying factors
      contributing to injury severity levels for different work zone configurations
      will allow for distinguishing mitigation methods for higher severity outcomes
      that best suit each of the depicted work zone layouts. This can be accomplished
      through the implementation of specific safety measures based on the specific
      configuration of a work zone as a potential crash location. Elasticity analysis
      suggests that partial control of access, roadways classified as rural, crashes
      during evening times, crashes during weekends, and curved roadways are key
      factors that increase the likelihood of severe outcomes. Also, the effects of
      several covariates were found to vary across the different work zone
      configurations.

PMID- 29207312
TI  - Investigating the spatial characteristics of the crossmodal interaction between
      nociception and vision using gaze direction.
AB  - The present study investigated the influence of nociceptive stimuli on visual
      stimuli processing according to the relative spatial congruence between the two
      stimuli of different sensory modalities. Participants performed temporal order
      judgments on pairs of visual stimuli, one presented near the hand on which
      nociceptive stimuli were occasionally applied, the other one either to its left
      or to its right. The visual hemifield in which the stimulated hand and the near
      visual stimulus appeared was manipulated by changing gaze direction. The
      stimulated hemibody and the stimulated visual hemifield were therefore either
      congruent or incongruent, in terms of anatomical locations. Despite the changes
      in anatomical congruence, judgments were always biased in favor of the visual
      stimuli presented near the stimulated hand. This indicates that nociceptive
      visual interaction may rely on a realignment of the respective initial anatomical
      representations of the somatic and retinotopic spaces toward an integrated,
      multimodal representation of external space.

PMID- 29207310
TI  - CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel
      cancer therapy.
AB  - Chemokines are proteins which induce chemotaxis, promote differentiation of
      immune cells, and cause tissue extravasation. Given these properties, their role
      in anti-tumor immune response in the cancer environment is of great interest.
      Although immunotherapy has shown clinical benefit for some cancer patients, other
      patients do not respond. One of the mechanisms of resistance to checkpoint
      inhibitors may be chemokine signaling. The CXCL9, -10, -11/CXCR3 axis regulates
      immune cell migration, differentiation, and activation, leading to tumor
      suppression (paracrine axis). However, there are some reports that show
      involvements of this axis in tumor growth and metastasis (autocrine axis). Thus,
      a better understanding of CXCL9, -10, -11/CXCR3 axis is necessary to develop
      effective cancer control. In this article, we summarize recent evidence regarding
      CXCL9, CXCL10, CXCL11/CXCR3 axis in the immune system and discuss their potential
      role in cancer treatment.

PMID- 29207313
TI  - Regulation of host-pathogen interactions via the post-transcriptional Csr/Rsm
      system.
AB  - A successful colonization of specific hosts requires a rapid and efficient
      adaptation of the virulence-relevant gene expression program by bacterial
      pathogens. An important element in this endeavor is the Csr/Rsm system. This
      multi-component, post-transcriptional control system forms a central hub within
      complex regulatory networks and coordinately adjusts virulence properties with
      metabolic and physiological attributes of the pathogen. A key function is
      elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous
      target mRNAs, many of which encode crucial virulence factors, and alters their
      translation, stability or elongation of transcription. Recent studies highlighted
      that important colonization factors, toxins, and bacterial secretion systems are
      under CsrA/RsmA control. CsrA/RsmA deficiency impairs host colonization and
      attenuates virulence, making this post-transcriptional regulator a suitable drug
      target. The CsrA/RsmA protein can be inactivated through sequestration by non
      coding RNAs, or via binding to specific highly abundant mRNAs and interacting
      proteins. The wide range of interaction partners and RNA targets, as well as the
      overarching, interlinked genetic control circuits illustrate the complexity of
      this regulatory system in the different pathogens. Future work addressing spatio
      temporal changes of Csr/Rsm-mediated control during the course of an infection
      will help us to understand how bacteria reprogram their expression profile to
      cope with continuous changes experienced in colonized niches.

PMID- 29207314
TI  - Enzyme evolution: innovation is easy, optimization is complicated.
AB  - Enzymes have been evolving to catalyze new chemical reactions for billions of
      years, and will continue to do so for billions more. Here, we review examples in
      which evolutionary biochemists have used big data and high-throughput
      experimental tools to shed new light on the enormous functional diversity of
      extant enzymes, and the evolutionary processes that gave rise to it. We discuss
      the role that gene loss has played in enzyme evolution, as well as the more
      familiar processes of gene duplication and divergence. We also review insightful
      studies that relate not only catalytic activity, but also a host of other
      biophysical and cellular parameters, to organismal fitness. Finally, we provide
      an updated perspective on protein engineering, based on our new-found
      appreciation that most enzymes are sloppy and mediocre.

PMID- 29207315
TI  - 8-oxoguanine DNA glycosylase (Ogg1) controls hepatic gluconeogenesis.
AB  - Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and
      is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the
      base excision repair pathway. Here, we tested the hypothesis that changes in
      liver metabolism as under fasting/feeding conditions would be sensed by liver
      mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild
      type (WT) and ogg1-/- mice were either fed ad libitum or subjected to fasting for
      24h, and the corresponding effects on liver gene expression, DNA damage, as well
      as serum values were analyzed. Ogg1 deficient mice fed ad libitum exhibited
      hyperglycemia, elevated insulin levels and higher liver glycogen content as well
      as increased accumulation of 8oxoG in mtDNA compared to age- and gender matched
      WT mice. Interestingly, these phenotypes were absent in ogg1-/- mice during
      fasting. Gene expression and functional analyses suggest that the diabetogenic
      phenotype in the ogg1-/- mice is due to a failure to suppress gluconeogensis in
      the fed state. The ogg1-/- mice exhibited reduced mitochondrial electron
      transport chain (ETC) capacity and a combined low activity of the pyruvate
      dehydrogenase (PDH), alluding to inefficient channeling of glycolytic products
      into the citric acid cycle. Our data demonstrate a physiological role of base
      excision repair that goes beyond DNA maintenance, and implies that DNA repair is
      involved in regulating metabolism.

PMID- 29207316
TI  - Hafnium(IV) triflate as a potent catalyst for selective 1-O-deacetylation of
      peracetylated saccharides.
AB  - An efficient method for selective anomeric deacetylation of peracetylated mono-,
      di-, and trisaccharides has been developed by using 2 mol% Hf(OTf)4 as catalyst
      in acetonitrile. Employment of ultrasonic irradiation could significantly
      accelerate the reaction rate. Mechanistic study confirmed the hydrolysis nature
      of this reaction, and NMR experimental data suggested that multiple peracetylated
      saccharide molecules may ligate to Hf(IV) cation primarily via the anomeric
      acetate to promote its specific hydrolysis.

PMID- 29207317
TI  - Public attitudes towards psychiatrists in the metropolitan area of Hanoi,
      Vietnam.
AB  - OBJECTIVES: Mental health associated stigmatization remains problematic in low
      and middle-income countries, thus preventing patients from adequate access to
      psychiatric care. Public attitudes towards psychiatrists have not been examined
      in many countries, especially not in Vietnam where merely one psychiatrist per
      300.000 population is available. The study aims to explore attitudes towards
      psychiatrists in the Hanoi municipality and to identify socio-demographical
      factors that influence these attitudes. METHODS: Between April and August 2013, a
      general population-based survey was carried out in the greater Hanoi area,
      Vietnam. The sample of 817 participants was stratified according to the latest
      Vietnamese census (2009) and micro-census (2013) with regards to socio
      demographic factors. Multivariate analyses were conducted to determine the
      influence of these factors on attitudes towards psychiatrists. RESULTS: Gender
      and religious beliefs significantly influenced public attitudes towards
      psychiatrists. Male participants reported significantly more negative perception
      towards psychiatrists compared to female respondents. Participants following a
      religion reported significantly more negative attitudes toward psychiatrists than
      those without self-reported religious attainment. CONCLUSIONS: Negative attitudes
      towards psychiatrists are associated with religious beliefs and gender
      affiliation in the greater Hanoi area. A strategy that involves religious
      institutions in raising awareness about mental health issues while considering
      public's socio-cultural attitudes may pave the way for greater potentialities of
      adequate psychiatric care, destigmatize the mental health system, and care
      provider.

PMID- 29207318
TI  - HER2 copy number of circulating tumour DNA functions as a biomarker to predict
      and monitor trastuzumab efficacy in advanced gastric cancer.
AB  - BACKGROUND: HER2 status is significant to trastuzumab therapy; however, it is
      difficult to determine HER2 status accurately with few pieces of biopsies from
      advanced gastric cancer (AGC) due to highly heterogeneity and invasive behaviour,
      which will be investigated in this study. METHODS: Fifty-six patients with AGC
      were included in this study. Primary tumour tissues and matched plasmas before
      medication from 36 patients were retrospectively collected, and the other 20
      patients with primary tumour tissues and paired plasmas were prospectively
      collected. HER2 expression and amplification in 56 tumour tissues were determined
      by immunohistochemistry (IHC) and dual in situ hybridisation (DISH), and HER2
      copy number in 135 circulating tumour DNAs (ctDNAs) was judged by next-generation
      sequencing. RESULTS: For tumour tissues, HER2 amplification by DISH was most
      commonly found in patients with HER2 score 3+by IHC. For plasmas, HER2
      amplification defined as HER2 copy number >2.22 was identified in 26 of 56
      patients. There was a high concordance of HER2 amplification between ctDNA and
      tumour tissues, suggesting that ctDNA could function as an alternative to screen
      HER2-targeted population. Moreover, the changes of HER2 copy number in ctDNA
      could efficiently monitor trastuzumab efficacy, the power of which was superior
      to commonly used markers carcinoembryonic antigen (CEA) and CA199, suggesting its
      potential role in clinical practice. CONCLUSION: ctDNA for HER2 analysis was
      strongly recommended to serve as a surrogate to screen trastuzumab-suitable
      population and monitor trastuzumab efficacy.

PMID- 29207319
TI  - Phytochemical variation among the traditional Chinese medicine Mu Dan Pi from
      Paeonia suffruticosa (tree peony).
AB  - Mu Dan Pi is a traditional Chinese medicine used to treat inflammation, cancer,
      allergies, diabetes, angiocardiopathy, and neurodegenerative diseases. In this
      study, the metabolome variation within Mu Dan Pi collected from 372 tree peony
      cultivars was systematically investigated. In total, 42 metabolites were
      identified, comprising of 14 monoterpene glucosides, 11 tannins, 8 paeonols, 6
      flavonoids, and 3 phenols. All cultivars revealed similar metabolite profiles,
      however, they were further classified into seven groups on the basis of their
      varying metabolite contents by hierarchical cluster analysis. Traditional
      cultivars for Mu Dan Pi were found to have very low metabolite contents, falling
      into clusters I and II. Cultivars with the highest amounts of metabolites were
      grouped in clusters VI and VII. Five potential cultivars, namely, 'Bai Yuan Qi
      Guan', 'Cao Zhou Hong', 'Da Zong Zi', 'Sheng Dan Lu', and 'Cheng Xin', with high
      contents of monoterpene glycosides, tannins, and paeonols, were further screened.
      Interestingly, the majority of investigated cultivars had relatively higher
      metabolite contents compared to the traditional medicinal tree peony cultivars.

PMID- 29207320
TI  - PTP1B inhibitory and cytotoxic C-24 epimers of Delta28-24-hydroxy stigmastane
      type steroids from the brown alga Dictyopteris undulata Holmes.
AB  - Ten stigmastane-type steroids bearing unusual Delta28-24-hydroxy side chains,
      dictyopterisins A-J, including three pairs of C-24 epimers, dictyopterisins B/C,
      F/G, and I/J, were isolated from the brown alga Dictyopteris undulata Holmes,
      together with two previously reported analogues, (24S)- and (24R)-saringosterol.
      Their structures were elucidated on the basis of extensive spectroscopic
      analysis, with their absolute configurations at the stereogenic center C-24 of
      the side chain being assigned by a direct comparison of 1H NMR data with those of
      related known compounds. The absolute configurations of the steroidal nuclei of
      dictyopterisins A, B, and H were determined using the modified Mosher's method.
      The mixture of dictyopterisins D and E and dictyopterisin I exhibited promising
      PTP1B inhibitory activities with IC50 values of 1.88 and 3.47 MUM, respectively,
      comparable to the positive control oleanolic acid (IC50, 2.78 MUM). In addition,
      the mixture of dictyopterisins D and E and dictyopterisins F-J displayed
      significant cytotoxicities against the human cancer cell lines HL-60 (IC50 from
      1.02 to 2.70 MUM) and A-549 (IC50 from 1.35 to 2.85 MUM).

PMID- 29207321
TI  - A multi-institutional registry of pediatric hospital-acquired thrombosis cases:
      The Children's Hospital-Acquired Thrombosis (CHAT) project.
AB  - BACKGROUND: Pediatric hospital-acquired venous thromboembolism (HA-VTE) rates
      have increased dramatically. To achieve generalizable knowledge in the derivation
      and validation of HA-VTE risk factors and risk prediction models and inform
      future risk-stratified prevention strategies, multi-institutional studies are
      needed. OBJECTIVES: This paper presents an investigator-initiated, multicenter
      pediatric case-cohort study designed to identify risk factors for HA-VTE to
      create a HA-VTE risk prediction model. METHODS: A registry, which houses
      pertinent variables from HA-VTE subjects and non-HA-VTE controls, was created for
      the Children's Hospital-Acquired Thrombosis (CHAT) study. Specific variables from
      the registry associated with HA-VTE risk will be identified using multivariable
      regression to create a pediatric HA-VTE risk prediction model to be prospectively
      validated. RESULTS: Seven large pediatric institutions have entered over 600 HA
      VTE subjects aged 0-21years of age into the registry. Subjects showed a male
      predominance (57%), a median age of three years (IQR 0.3-13) and were most likely
      admitted to an intensive care unit (57%) at VTE diagnosis. Median time to HA-VTE
      was 10days after admission. The most prevalent risk factors include central
      venous catheters (80%), surgery (43%), systemic steroids (31%), congenital heart
      disease (27%), infection (14%) and cancer (13%). CONCLUSIONS: CHAT, with its
      creation of a risk prediction model with prospective validation using the CHAT
      registry, is a novel study design and will be the first step in identifying safe
      and effective strategies to decrease HA-VTE in children by helping define the
      highest risk population for initial, or more aggressive, thromboprophylaxis
      efforts.

PMID- 29207323
TI  - Overcoming obstacles in the tumor microenvironment: Recent advancements in
      nanoparticle delivery for cancer theranostics.
AB  - Despite rapid advancements in the field of nanotechnology, there is mounting
      frustration in the scientific community regarding the translational impact of
      nanomedicine. Modest therapeutic performance of FDA-approved nanomedicines
      combined with multiple disappointing clinical trials (such as phase III HEAT
      trial) have raised questions about the future of nanomedicine. Encouraging
      breakthroughs, however, have been made in the last few years towards the
      development of new classes of nanoparticles that can respond to tumor
      microenvironmental conditions and successfully deliver therapeutic agents to
      cancer cells. Concurrently, a great deal of effort has also been devoted to alter
      various parameters of tumor pathophysiology to pre-treat tumors before
      nanoparticles are administered. Such 'priming' treatments improve access of the
      systemically administered agents to the tumor and promote drug penetration into
      the deeper layers of tumor tissue. This review will highlight recent advances in
      cancer nanomedicine exploiting both nanoparticle design and tumor
      microenvironment modification; and provide a critical perspective on the future
      development of nanomedicine delivery in oncology.

PMID- 29207322
TI  - Identification of a "VTE-rich" population in pediatrics - Critically ill children
      with central venous catheters.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) is rising among
      inpatients in US hospitals, especially among kids with central venous catheters
      (CVCs) in the pediatric intensive care unit (PICU). OBJECTIVES: To identify a sub
      group of "VTE-rich" population among PICU children, and to assess the effect of
      VTE on morbidity and mortality. METHODS: Data was extracted from a multicenter
      Virtual PICU Database, or VPS, for children with a CVC and presence of a VTE. The
      primary outcome variable was all cause mortality and secondary outcome measure
      was prolonged mechanical ventilation. Primary diagnoses and Pediatric risk of
      mortality 2 (PIM 2) score were also recorded. RESULTS: The database identified
      158,299 PICU patients who had a CVC. A total of 1602 patients had VTE (103 per
      10,000 PICU patients). Multivariate analysis showed increased risk of VTE in
      patients who were <1year old (OR 1.48; 1.30-1.68), mechanically ventilated (OR
      2.48; 2.07-2.98), had either a diagnostic (OR 2.32; 1.94-2.78) or therapeutic
      cardiac catheterization (OR 2.06; 1.66-2.55), PICC (OR 3.91; 3.50-4.37), and
      percutaneous CVC (OR 3.99; 3.48-4.61). Primary diagnoses associated with VTE were
      endocrinologic, immunologic, and gastrointestinal disorders. PICU patients with
      CVC and VTE had increased odds of mortality (OR 1.71; 1.47-2.00) after adjusting
      for factors associated with mortality, and fewer Ventilator Free Days (VFD) than
      patients without VTE. CONCLUSIONS: Critically ill children with CVC have a
      significant risk of developing VTE. Identification of the above "VTE-rich"
      population may aid in design of clinical trials aimed at prevention of VTE among
      hospitalized PICU children.

PMID- 29207324
TI  - Microenvironments to study migration and somal translocation in cortical neurons.
AB  - Migrating post-mitotic neurons of the developing cerebral cortex undergo terminal
      somal translocation (ST) when they reach their final destination in the cortical
      plate. This process is crucial for proper cortical layering and its perturbation
      can lead to brain dysfunction. Here we present a reductionist biomaterials
      platform that faithfully supports and controls the distinct phases of terminal ST
      in vitro. We developed microenvironments with different adhesive molecules to
      support neuronal attachment, neurite extension, and migration in distinct
      manners. Efficient ST occurred when the leading process of migratory neurons
      crossed from low-to high-adhesive areas on a substrate, promoting spreading of
      the leading growth cone. Our results indicate that elementary adhesive cell
      substrate interactions strongly influence migratory behavior and the final
      positioning of neurons during their developmental journey. This in vitro model
      allows advanced experimentation to reveal the microenvironmental requirements
      underlying cortical layer development and disorders.

PMID- 29207325
TI  - Prediction of miscarriage in women with viable intrauterine pregnancy-A
      systematic review and diagnostic accuracy meta-analysis.
AB  - Both ultrasound and biochemical markers either alone or in combination have been
      described in the literature for the prediction of miscarriage. We performed this
      systematic review and meta-analysis to determine the best combination of
      biochemical, ultrasound and demographic markers to predict miscarriage in women
      with viable intrauterine pregnancy. The electronic database search included
      Medline (1946-June 2017), Embase (1980-June 2017), CINAHL (1981-June 2017) and
      Cochrane library. Key MESH and Boolean terms were used for the search. Data
      extraction and collection was performed based on the eligibility criteria by two
      authors independently. Quality assessment of the individual studies was done
      using QUADAS 2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised
      Tool) and statistical analysis performed using the Cochrane systematic review
      manager 5.3 and STATA vs.13.0. Due to the diversity of the combinations used for
      prediction in the included papers it was not possible to perform a meta-analysis
      on combination markers. Therefore, we proceeded to perform a meta-analysis on
      ultrasound markers alone to determine the best marker that can help to improve
      the diagnostic accuracy of predicting miscarriage in women with viable
      intrauterine pregnancy. The systematic review identified 18 eligible studies for
      the quantitative meta-analysis with a total of 5584 women. Among the ultrasound
      scan markers, fetal bradycardia (n=10 studies, n=1762 women) on hierarchical
      summary receiver operating characteristic showed sensitivity of 68.41%,
      specificity of 97.84%, positive likelihood ratio of 31.73 (indicating a large
      effect on increasing the probability of predicting miscarriage) and negative
      likelihood ratio of 0.32. In studies for women with threatened miscarriage (n=5
      studies, n=771 women) fetal bradycardia showed further increase in sensitivity
      (84.18%) for miscarriage prediction. Although there is gestational age dependent
      variation in the fetal heart rate, a plot of fetal heart rate cut off level
      versus log diagnostic odds ratio showed that at <=110 beat per minutes the
      diagnostic power to predict miscarriage is higher. Other markers of intra uterine
      hematoma, crown rump length and yolk sac had significantly decreased predictive
      value. Therefore in women with threatened miscarriage and presence of fetal
      bradycardia on ultrasound scan, there is a role for offering repeat ultrasound
      scan in a week to ten days interval.

PMID- 29207326
TI  - In silico prediction of potential vaccine candidates on capsid protein of human
      bocavirus 1.
AB  - Human bocavirus 1 (HBoV1) is a newly identified parvovirus that causes serious
      respiratory infection among children across the globe. Aim of the present study
      was to predict immunogenic residues located on the VP2 protein of HBoV1 towards
      development of epitope based vaccines. Several computational tools were employed
      to predict epitopes (bothT and B cell restricted) with stringent regulation for
      the improvement of confidence. After meticulous analysis, the peptide
      "TTPWTYFNFNQY" was identified as potential candidate for development of
      preventive vaccine. Of note, the epitope "TTPWTYFNFNQY" was found to be
      recognized by fifteen different alleles belonging to seven HLA supertypes (A1,
      A3, A24, A26, B7, B58 and B62). Further, mutational variability analysis pointed
      that most of the amino acids were well conserved. Docking scores obtained from
      ClusPro and Autodock Vina for selected epitopes displayed energetically favorable
      and stable interaction of peptide-HLA-I complexes. The core peptide "LLYQMPFFL"
      was found to recognize by wide range of HLA class II allele recognition thereby
      qualified as candidate for therapeutic vaccine. Five distinct linear peptides
      (withT cell epitope superimposition) belonging to B cells were identified in the
      VP2 protein. Further attention on the enlisted epitopes may shed light on the
      path for development of diagnostic, therapeutic and preventive tools against
      HBoV1 infection. Additionally, the predicted epitopes may help us to address the
      original antigenic sin phenomena observed during consecutive HBoV2-4 infection.

PMID- 29207327
TI  - Molecular mechanism of LPS-induced TNF-alpha biosynthesis in polarized human
      macrophages.
AB  - In response to environmental stimuli such as granulocyte-macrophage or macrophage
      colony stimulating factor (GM-CSF/M-CSF), macrophages (MPhi) can acquire distinct
      functional phenotypes that control inflammatory processes on the one hand and
      contribute to a broad spectrum of pathologies on the other. Potential
      intervention strategies will require an understanding of the signalling processes
      that are associated with macrophage polarization. In the present study, we show
      that M-MPhi produce more IFN-beta and IL-10 and a lot less TNF-alpha than do GM
      MPhi in response to LPS. To define the molecular mechanisms that underlie the
      biosynthesis of TNF-alpha we carried out a detailed investigation of the LPS
      induced activation of the canonical and non-canonical myeloid differentiation
      primary response 88 (MyD88)-dependent signal transduction pathways as well as the
      TIR-domain-containing adapter-inducing interferon-beta (TRIF)-dependent pathway.
      Our results show that all three pathways are activated in both cell types and
      that the activation is more pronounced in M-MPhi. While IL-10 was found to
      interfere with TNF-alpha production in M-MPhi, we exclude a decisive role for IFN
      beta in this respect. Furthermore, we demonstrate that TNF-alpha mRNA is markedly
      destabilized in M-MPhi and that expression of the mRNA destabilizing protein
      tristetraprolin is greatly enhanced in these cells. Collectively, our study
      suggests that differential effects of LPS on TNF-alpha mRNA turnover and on
      signal transduction pathways influence the amount of TNF-alpha finally produced
      by GM-MPhi and M-MPhi.

PMID- 29207328
TI  - Age estimation approaches using cranial suture closure: A validation study on a
      Thai population.
AB  - Cranial suture closure, one of the most commonly used age estimation methods, for
      decades, however, is often viewed with caution and its reliability is still
      debated. Few methods of estimating age using the skeleton, especially cranial
      suture, have been tested on Thais. This study aims to test the traditional aging
      techniques using cranial suture closure on Thai individuals in order to identify
      the error rate of each method when applied to a Thai sample. Meindl and Lovejoy
      (1985), Acsadi and Nemeskeri (1970), and Mann (1991) methods were applied to 175
      Thai dry crania. Bias and inaccuracy in the Meindl and Lovejoy, Acsadi and
      Nemeskeri, and Mann methods resulted in overestimation in young adults and
      underestimation in older individuals with an inaccuracy range of approximately 13
      22 years. The Mann method approached 100% in predicting age in older males, but
      the method did not fare as well on Thai females. The results confirm inter
      population variation does exist. Additionally, differences in age composition
      between populations used to develop the methods and Thais may lead to an increase
      in error. This study indicates that these three aging methods should be used in
      conjunction with other techniques. Further research which develops specific
      methods for Thais might give better results for age estimation.

PMID- 29207329
TI  - Tensile rupture of medial arterial tissue studied by X-ray micro-tomography on
      stained samples.
AB  - Detailed characterization of damage and rupture mechanics of arteries is one the
      current challenges in vascular biomechanics, which requires developing suitable
      experimental approaches. This paper introduces an approach using in situ tensile
      tests in an X-ray micro-tomography setup to observe mechanisms of damage
      initiation and progression in medial layers of porcine aortic samples. The
      technique requires the use of sodium polytungstate as a contrast agent, of which
      the conditions for use are detailed in this paper. Immersion of the samples
      during 24h in a 15g/L concentrated solution provided the best compromise for
      viewing musculo-elastic units in this tissue. The process of damage initiation,
      delamination and rupture of medial tissue under tensile loading was observed and
      can be described as an elementary process repeating several times until complete
      failure. This elementary process initiates with a sudden mode I fracture of a
      group of musculo-elastic units, followed by an elastic recoil of these units,
      causing mode II separation of these, hence a delamination plane. The presented
      experimental approach constitutes a basis for observation of other constituents,
      or for investigations on other tissues and damage mechanisms.

PMID- 29207330
TI  - Steps towards 'drop-in' biofuels: focusing on metabolic pathways.
AB  - The past decade has witnessed rapid advance in microbial production of 'drop-in'
      biofuels from renewable resources. Various biosynthetic pathways have been
      constructed to produce biofuels with diverse structures, and multiple metabolic
      engineering strategies have been developed to increase biofuel titers, yields,
      productivities and system robustness. In this review, we intend to give a brief
      but comprehensive overview of the most recent progresses on four essential
      pathways leading to 'drop-in' biofuel production, with an emphasis on the
      metabolic pathway efficiencies and biofuel structures. Furthermore, we also
      provide an insightful discussion on optimization strategies to improve the
      robustness of the microbial platforms for biofuel production.

PMID- 29207331
TI  - Use of bacterial co-cultures for the efficient production of chemicals.
AB  - The microbial production of chemicals has traditionally relied on a single
      engineered microbe to enable the complete bioconversion of substrate to final
      product. Recently, a growing fraction of research has transitioned towards
      employing a modular co-culture engineering strategy using multiple microbes
      growing together to facilitate a divide-and-conquer approach for chemical
      biosynthesis. Here, we review key success stories that leverage the unique
      advantages of co-culture engineering, while also addressing the critical concerns
      that will limit the wide-spread implementation of this technology. Future studies
      that address the need to monitor and control the population dynamics of each
      strain module, while maintaining robust flux routes towards a wide range of
      desired products will lead the efforts to realize the true potential of co
      culture engineering.

PMID- 29207332
TI  - A model assessment method for predicting structural fatigue life using Lamb
      waves.
AB  - This paper presents a study on model assessment for predicting structural fatigue
      life using Lamb waves. Lamb wave coupon testing is performed for model
      development. Three damage sensitive features, namely normalized energy, phase
      change, and correlation coefficient are extracted from Lamb wave data and are
      used to quantify the crack size. Four data-driven models are proposed. The
      average relative error and the probability of detection (POD) are proposed as two
      measures to evaluate the performance of the four models. To study the influence
      of model choice on the probabilistic fatigue life prediction, probability density
      functions of the actual crack size are obtained from the POD models given the
      Lamb wave data. Crack growth model parameters are statistically identified using
      Bayesian parameter estimation with Markov chain Monte Carlo simulations. The
      model assessment and the influence of model choice on fatigue life prediction are
      made using both coupon testing data with artificial cracks and realistic lap
      joint testing data with naturally developed cracks.

PMID- 29207333
TI  - Acute in vitro neurotoxicity of some pyrethroids using microelectrode arrays.
AB  - Pyrethroid-mediated changes on microelectrode array (MEA) parameters, such as
      mean firing rate (MFR), mean burst rate (MBR), and number of active channels
      (nAC) were investigated by exposing neuronal networks to cumulative
      concentrations (0.01, 0.1, 1, 10, and 100MUM) of pyrethroids (Type-1, bifenthrin
      and permethrin; Type-2, beta-cyfluthrin, cypermethrin, deltamethrin, and lambda
      cyhalothrin). The average MFR, MBR, and nAC increased for all pyrethroids (except
      nAC for deltamethrin) at lower concentrations and decreased at higher
      concentrations. The increase in the average MFR, MBR, and nAC was not
      statistically significant in most of the cases. Increase in MFR, MBR, and nAC was
      observed in 19/19, 18/19, and 12/19 individual experiments, respectively, at
      lower concentrations. The IC50s calculated on MEA parameters were more or less
      similar. The relative potencies calculated on the IC50s of MEA parameters had a
      strong positive correlation. These observations indicate that the MEA parameters
      MFR, MBR, and nAC follow the same trend for pyrethroid-mediated changes, and
      provide a similar outcome. The rank orders of relative potencies on the IC50s of
      the MEA parameters distinguish type-1 pyrethroids from type-2 pyrethroids, with
      type-2 being more potent. As increase in MFR at the lower concentrations of
      pyrethroids was observed in all the individual experiments (19/19), it may be
      considered as the characteristic effect of pyrethroids on neuronal excitability.

PMID- 29207334
TI  - PeptideNavigator: An interactive tool for exploring large and complex data sets
      generated during peptide-based drug design projects.
AB  - There is growing interest in peptide-based drug design and discovery. Due to
      their relatively large size, polymeric nature, and chemical complexity, the
      design of peptide-based drugs presents an interesting "big data" challenge. Here,
      we describe an interactive computational environment, PeptideNavigator, for
      naturally exploring the tremendous amount of information generated during a
      peptide drug design project. The purpose of PeptideNavigator is the presentation
      of large and complex experimental and computational data sets, particularly 3D
      data, so as to enable multidisciplinary scientists to make optimal decisions
      during a peptide drug discovery project. PeptideNavigator provides users with
      numerous viewing options, such as scatter plots, sequence views, and sequence
      frequency diagrams. These views allow for the collective visualization and
      exploration of many peptides and their properties, ultimately enabling the user
      to focus on a small number of peptides of interest. To drill down into the
      details of individual peptides, PeptideNavigator provides users with a
      Ramachandran plot viewer and a fully featured 3D visualization tool. Each view is
      linked, allowing the user to seamlessly navigate from collective views of large
      peptide data sets to the details of individual peptides with promising property
      profiles. Two case studies, based on MHC-1A activating peptides and MDM2 scaffold
      design, are presented to demonstrate the utility of PeptideNavigator in the
      context of disparate peptide-design projects.

PMID- 29207335
TI  - Tamoxifen a pioneering drug: An update on the therapeutic potential of tamoxifen
      derivatives.
AB  - Tamoxifen (ICI 46 474), trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2
      diphenylbut-1-ene, is the most commonly used drug for the treatment of estrogen
      receptor positive breast cancer and has been saving lives worldwide for the past
      four decades. Tamoxifen is considered a pioneering drug due to its ubiquitous use
      in both treatment and chemoprevention of breast cancer and also for research
      addressing novel selective estrogen receptor modulators (SERMs). Tamoxifen is
      cost effective, lifesaving, and devoid of major side effects in the majority of
      patients. The discovery of tamoxifen metabolites such as 4-hydroxy tamoxifen, N
      desmethyl tamoxifen, and endoxifen has facilitated understanding of tamoxifen's
      and its metabolites' mechanisms of action in breast cancer therapy. Continuous
      efforts are being made by both industry and academia to synthesize novel
      tamoxifen derivatives in order to better understand the mechanism of this drug's
      action and to generate new agents with reduced side effects for many therapeutic
      targets. This review article comprises the tamoxifen derivatives reported in the
      literature in the last few years and we anticipate that it will assist medicinal
      chemists in the synthesis of novel and pharmacologically potent agents for
      various therapeutic targets.

PMID- 29207336
TI  - Cytotoxicity, molecular modeling, cell cycle arrest, and apoptotic induction
      induced by novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcones.
AB  - Novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one
      derivatives were synthesized and their structures were confirmed by different
      spectral tools. Cytotoxicity test revealed that some compounds exhibited strong
      to moderate effect, while others showed weak action against different cancer cell
      lines (MCF7, A549, HCT116, and Hepg2). Breast carcinoma revealed higher
      sensitivity toward all derivatives especially compounds 5 and 8 which offered the
      lowest IC50 values (50.05, and 27.15 MUg/ml) respectively, relative to the
      positive control 5-fluorouracil (5-FU) (IC50 = 178 MUg/ml). In addition, the two
      compounds exhibited less toxic effect toward normal melanocytes (HFB4). Several
      theoretical and experimental studies were done to reveal the molecular mechanisms
      that control breast carcinoma metastasis using the two promising novels 5 and 8.
      Docking simulation studies against the two proteins EGFR and DHFR demonstrate
      that compound 8 showed higher binding affinity toward the two proteins more than
      compound 5, suggesting that trimethoxy groups may be responsible for this higher
      activity through the formation of five hydrogen bonding with the active domain
      (4r3r) and other four interactions with the active domain (1dls). Real time PCR
      assay illustrates that the two compounds up regulated BAX, p53, caspase-3 genes
      and down regulated BCL2, MMP1, CDK4 ones. In addition, it was noted that compound
      8 was more effective in gene regulation and apoptotic induction than compound 5.
      Also, flow cytometer analysis demonstrates that both compounds 5 and 8 induced
      cell growth arrest at G1 phase and thus, inhibit G1/S transition and cell cycle
      progression. In addition, both compounds stimulate apoptotic death of breast
      cells significantly to reach 8.72%, and 17.28% respectively, compared to their
      control (0.55%). Apoptotic induction of breast cells was enhanced effectively
      through activation of caspase-3 by compound 8 using Elisa assay.

PMID- 29207337
TI  - Quinoxaline: An insight into the recent pharmacological advances.
AB  - Quinoxaline, a fused heterocycle of benzene and pyrazine rings has gained
      considerable attention in the field of contemporary medicinal chemistry. The
      moiety is of substantial importance because of its wide array of pharmacological
      activities viz. anti-cancer, antimalarial, anti-inflammatory, antimicrobial, anti
      HIV etc. Diversely substituted quinoxalines are important therapeutic agents in
      the pharmaceutical industry. This review focusses on the quinoxaline derivatives
      developed during the last decennial period and their biomedical applications. A
      compilation of patents on quinoxaline is also included herein.

PMID- 29207338
TI  - Synthesis and bio-inspired optimization of drimenal: Discovery of chiral drimane
      fused oxazinones as promising antifungal and antibacterial candidates.
AB  - The synthesis of antifungal natural product drimenal was accomplished. Bio
      inspired optimization protruded chiral 8-(R)-drimane fused oxazinone D as a lead,
      considering favorable physicochemical profiles for novel pesticides. The improved
      scalable synthesis of scaffold D was implemented by Hofmann rearrangment under
      mild conditions. Detailed structural optimization was discussed for both
      antifungal and antibacterial exploration. Substituted groups (SGs) with C3~C5
      hydrocarbon chain are recommended for exploration of antifungal agents, while
      substituents with C4~C6 carbon length are preferred for antibacterial
      ingredients. The chiral drimane fused oxazinone D8 was selected as a promising
      antifungal candidate against Botrytis cirerea, with an EC50 value of 1.18 mg/L,
      with the enhancement of up to >25 folds and >80 folds than the mother compound D,
      and acyclic counterpart AB5, respectively. The in vivo bioassay confirmed much
      better preservative effect of D8 than that of Carbendazim. The chiral oxazinone
      variant D10 possessed prominent antibacterial activity, with MIC values of 8 mg/L
      against both Bacillus subtilis and Ralstonia solanacearum, showing advantages
      over the positive control streptomycin sulfate.

PMID- 29207339
TI  - Structure-activity relationships for inhibitors of Pseudomonas aeruginosa
      exoenzyme S ADP-ribosyltransferase activity.
AB  - During infection, the Gram-negative opportunistic pathogen Pseudomonas aeruginosa
      employs its type III secretion system to translocate the toxin exoenzyme S (ExoS)
      into the eukaryotic host cell cytoplasm. ExoS is an essential in vivo virulence
      factor that enables P. aeruginosa to avoid phagocytosis and eventually kill the
      host cell. ExoS elicits its pathogenicity mainly via ADP-ribosyltransferase
      (ADPRT) activity. We recently identified a new class of ExoS ADPRT inhibitors
      with in vitro IC50 of around 20 MUM in an enzymatic assay using a recombinant
      ExoS ADPRT domain. Herein, we report structure-activity relationships of this
      compound class by comparing a total of 51 compounds based on a thieno [2,3
      d]pyrimidin-4(3H)-one and 4-oxo-3,4-dihydroquinazoline scaffolds. Improved
      inhibitors with in vitro IC50 values of 6 MUM were identified. Importantly, we
      demonstrated that the most potent inhibitors block ADPRT activity of native full
      length ExoS secreted by viable P. aeruginosa with an IC50 value of 1.3 MUM in an
      enzymatic assay. This compound class holds promise as starting point for
      development of novel antibacterial agents.

PMID- 29207340
TI  - Xanthine oxidase inhibitory activity of natural and hemisynthetic flavonoids from
      Gardenia oudiepe (Rubiaceae) in vitro and molecular docking studies.
AB  - Xanthine oxidase (XO), an enzyme widely distributed among mammalian tissues, is
      associated with the oxidation of xanthine and hypoxanthine to form uric acid.
      Reactive oxygen species are also released during this process, leading to
      oxidative damages and to the pathology called gout. Available treatments mainly
      based on allopurinol cause serious side effects. Natural products such as
      flavonoids may represent an alternative. Thus, a series of polymethoxyflavones
      isolated and hemisynthesized from the bud exudates of Gardenia oudiepe has been
      evaluated for in vitro XO inhibitory activity. Compounds 1, 2 and 3 were more
      active than the reference inhibitor, Allopurinol (IC50 = 0.25 +/- 0.004 MUM) with
      IC50 values of (0.004 +/- 0.001) MUM, (0.05 +/- 0.01) MUM and (0.09 +/- 0.003)
      MUM, respectively. Structure-activity relationships were established.
      Additionally, a molecular docking study using MOETM tool was carried out to
      establish the binding mode of the most active flavones with the enzyme, showing
      important interactions with its catalytic residues. These promising results,
      suggest the use of these compounds as potential leads for the design and
      development of novel XO inhibitors.

PMID- 29207341
TI  - DNA intercalators based on (1,10-phenanthrolin-2-yl)isoxazolidin-5-yl core with
      better growth inhibition and selectivity than cisplatin upon head and neck
      squamous cells carcinoma.
AB  - ((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2
      yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar
      cycloaddition methodology, as DNA intercalating agents and evaluated for their
      anticancer activity against human cervical carcinoma HeLa and head and neck
      squamous cells carcinoma cell lines. The synthesized compounds exhibited good
      cytotoxic activity with IC50 better than cisplatin, used as the main and
      effective treatment for HNSCC, and a 24.3-72.0-fold selectivity respect to the
      184B5 non-cancerous immortalized breast epithelial cell lines. Unwinding assay,
      circular dichroism data, and Uv-vis melting experiments confirmed that these
      compounds act as DNA intercalators with a binding constant in the order of 104 M
      1. Docking studies showed that both compounds can interact as intercalating agent
      with both poly-d(AT)2 and poly-d(GC)2, preferring an entrance by the minor groove
      of the poly-d(AT)2.

PMID- 29207342
TI  - Accelerated skin wound healing by selective 11beta-Hydroxylase (CYP11B1)
      inhibitors.
AB  - Previous studies have shown that inhibition of cortisol biosynthesis in skin
      leads to accelerated wound healing. Here, pyridylmethyl pyridine type 11beta
      hydroxylase (CYP11B1) inhibitors were optimized for topical application to avoid
      systemic side effects. The resulting very potent, non-toxic CYP11B1 inhibitor 14
      (IC50 = 0.8 nM) exhibited good selectivity over 11beta-HSD1, CYP17A1 and CYP19A1.
      The compound showed high stability toward human plasma (t1/2= > 150 min, as a
      substitute for wound fluid) and low stability toward HLS9 (t1/2 = 19 min) for
      rapid metabolic clearance after absorption. Compound 14 was able to accelerate
      wound healing in human skin.

PMID- 29207343
TI  - Development of novel anti-filarial agents using carbamo(dithioperoxo)thioate
      derivatives.
AB  - A series of novel carbamo(dithioperoxo)thioate derivatives have been prepared in
      excellent yield using a significantly fast, one-pot three component reaction and
      experimented for their potential as anti-filarial agents against model filarial
      nematode Setaria cervi. Among 23 compounds (4a-w) evaluated for the anti-filarial
      activities, five compounds (4a, 4b, 4c, 4d and 4h) have shown promising anti
      proliferative effects on the juvenile stage microfilariae (mf) as well as in
      adults in a time and dose dependent manner. Compound 4a was found most active
      against oocytes, mf and adult nematods as well as non-cytotoxic to the normal
      cells. It has been established that the anti-filarial activity of the compounds
      were observed due to the involvement of reactive oxygen species (ROS) and
      apoptosis. Several biochemical and microscopic experiments have been carried out
      to establish the fact that both intrinsic and extrinsic pathways of apoptosis
      contribute to the compound 4a mediated death phenomenon of the filarial
      nematodes.

PMID- 29207344
TI  - NOD1 and NOD2: Molecular targets in prevention and treatment of infectious
      diseases.
AB  - Nucleotide-binding oligomerization domain (NOD) 1 and NOD2 are pattern
      recognition receptors responsible for sensing fragments of bacterial
      peptidoglycan known as muropeptides. Stimulation of innate immunity by systemic
      or local administration of NOD1 and NOD2 agonists is an attractive means to
      prevent and treat infectious diseases. In this review, we discuss novel data
      concerning structural features of selective and non-selective (dual) NOD1 and
      NOD2 agonists, main signaling pathways and biological effects induced by NOD1 and
      NOD2 stimulation, including induction of pro-inflammatory cytokines, type I
      interferons and antimicrobial peptides, induction of autophagy, alterations of
      metabolism. We also discuss interactions between NOD1/NOD2 and Toll-like receptor
      agonists in terms of synergy and cross-tolerance. Finally, we review available
      animal data on the role of NOD1 and NOD2 in protection against infections, and
      discuss how these data could be applied in human infectious diseases.

PMID- 29207345
TI  - Water-in-oil Pickering emulsions stabilized by stearoylated microcrystalline
      cellulose.
AB  - HYPOTHESIS: Hydrophobic particles with static water contact angles larger than 90
      degrees  are more like to stabilize W/O Pickering emulsions. In particular, high
      internal phase Pickering emulsions (HIPEs) are of great interest for diverse
      applications. However, W/O HIPEs have rarely been realized using sustainable
      biopolymers. Herein, we used stearoylated microcrystalline cellulose (SMCC) to
      stabilize W/O Pickering emulsions and especially, W/O HIPEs. Moreover, these W/O
      HIPEs can be further used as platforms for the preparation of porous materials,
      such as porous foams. EXPERIMENTS: Stearoylated microcrystalline cellulose (SMCC)
      was prepared by modifying MCC with stearoyl chloride under heterogeneous
      conditions. Using SMCC as emulsifiers, W/O medium and high internal phase
      Pickering emulsions (MIPEs and HIPEs) with various organic solvents as continuous
      phases were prepared using one-step and two-step methods, respectively.
      Polystyrene (PS) foams were prepared after polymerization of oil phase using
      HIPEs as templates and their oil/water separation capacity were studied.
      FINDINGS: SMCC could efficiently stabilize W/O Pickering emulsions and HIPEs
      could only be prepared via the two-step method. The internal phase volume
      fraction of the SMCC-stabilized HIPEs reached as high as 89%. Diverse internal
      phase volume fractions led to distinct inner structures of foams with closed or
      open cells. These macroporous polystyrene (PS) foams demonstrated great potential
      for the effective absorption of organic solvents from underwater.

PMID- 29207346
TI  - Colloidal polymer particles as catalyst carriers and phase transfer agents in
      multiphasic hydroformylation reactions.
AB  - HYPOTHESIS: Colloidal particles have been used to covalently bind ligands for the
      heterogenization of homogeneous catalysts. The replacement of the covalent bonds
      by electrostatic interactions between particles and the catalyst could preserve
      the selectivity of a truly homogeneous catalytic process. EXPERIMENTS:
      Functionalized polymer particles with trimethylammonium moieties, dispersed in
      water, with a hydrophobic core and a hydrophilic shell have been synthesized by
      emulsion polymerization and have been thoroughly characterized. The ability of
      the particles with different monomer compositions to act as catalyst carriers has
      been studied. Finally, the colloidal dispersions have been applied as phase
      transfer agents in the multiphasic rhodium-catalyzed hydroformylation of 1
      octene. FINDINGS: The hydrodynamic radius of the particles has been shown to be
      around 100 nm, and a core-shell structure could be observed by atomic force
      microscopy. The polymer particles were proven to act as carriers for the water
      soluble hydroformylation catalyst, due to electrostatic interaction between the
      functionalized particles bearing ammonium groups and the sulfonated ligands of
      the catalyst. The particles were stable under the hydroformylation conditions and
      the aqueous catalyst phase could be recycled three times.

PMID- 29207347
TI  - A facile approach towards amino-coated ferroferric oxide nanoparticles for
      environmental pollutant removal.
AB  - A facile and environmental-friendly approach was developed to prepare magnetic
      nano-adsorbent for environmental pollutant removal. Based on the mussel-inspired
      polymerization, amino-coated Fe3O4 nanoparticles were fabricated by simply
      immersing Fe3O4 nanoparticles into an aqueous solution of catechol and
      hexanediamine with stirring at room temperature. The magnetic nano-adsorbent was
      characterized via Fourier transform infrared spectroscopy (FTIR), transmission
      electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer
      (VSM), thermo gravimetric analysis (TGA), and Brunauer-Emmett-Teller's test
      (BET). The effects of initial mole ratio of catechol/hexanediamine and coating
      time on the adsorption capacity were investigated, using Congo red as a model
      organic dye. Under the optimal preparation condition, the absorption capacity of
      the amino-coated Fe3O4 nanoparticles reached 97.3 mg/g for Congo red, and the
      adsorption reached about 80% of the equilibrium adsorption amount within 200 min.
      Adsorption kinetics and isotherm studies indicated that the absorption process
      fitted the pseudo-second-order kinetic and Langmuir isotherm models well.
      Besides, desired functional groups could be introduced onto the surface of Fe3O4
      nanoparticles, to tailor the adsorption capacity for Congo red, amaranths red,
      methylene blue and methylene violet. It is believed that the amino-coated
      magnetic nano-adsorbent prepared by the proposed method in this study has a good
      prospect for wastewater treatment.

PMID- 29207348
TI  - Experimental study of dynamic contact angles on rough hydrophobic surfaces.
AB  - Rough hydrophobic surfaces have many applications in industry and technology. An
      experimental study was done on the spreading dynamics of different concentrations
      of polyethylene glycol (PEG) solutions on rough Teflon plates with different
      roughness. The experiments were conducted using Wilhelmy plate method. The
      advancing dynamic contact angle was found to be weakly dependent of capillary
      number. However, the receding dynamic contact angle decreases with increasing
      capillary number. The degree of roughness on rough Teflon surface has an
      important role on dynamic contact angle. The dynamics of receding motion was
      found to follow the molecular-kinetic theory. A power law relation between the
      receding dynamic contact angle and the capillary number was also obtained.

PMID- 29207349
TI  - Chemically functionalized graphene for lubricant applications: Microscopic and
      spectroscopic studies of contact interfaces to probe the role of graphene for
      enhanced tribo-performance.
AB  - Shear-induced transfer of graphene on the contact interfaces was studied by
      microscopic and spectroscopic analyses of steel balls lubricated with chemically
      functionalized graphene-based mineral lube base oil (SN-150). The 3,5-di-tert
      butyl-4-hydroxybenzaldehyde (DtBHBA) grafted-graphene (Gr-DtBHBA) was prepared by
      two-steps approach using graphene oxide as a precursor. Chemical and structural
      features of Gr-DtBHBA are probed by FTIR, XPS, Raman, TGA, and HRTEM analyses.
      The van der Waals interaction between the tertiary-butyl group in the Gr-DtBHBA
      and hydrocarbon chains of mineral lube base oil facilitates the dispersion of Gr
      DtBHBA in the SN-150 lube base oil, which is very important for the optimized
      performance of Gr-DtBHBA as a lubricant additive. The minute dosing (0.2-0.8 mg
      mL-1) of the Gr-DtBHBA in the SN-150 lube base oil showed the significant
      reduction in the coefficient of friction (40%) and wear scar diameter (17%) under
      the rolling contact between steel balls. The microscopic and EDX analysis of the
      worn area suggested the role of Gr-DtBHBA nanosheets for enhanced tribo
      performance of the SN-150 lube base oil. A detailed Raman study of the worn area
      of steel ball revealed the deposition of a graphene-based tribo thin film in the
      forms of irregular patches. The shear-induced deposition of graphene thin film on
      the contact interfaces reduced the friction and protected the tribo-surfaces
      against the wear.

PMID- 29207350
TI  - Mobile genetic elements and antibiotic resistance in mine soil amended with
      organic wastes.
AB  - Metal resistance has been associated with antibiotic resistance due to co- or
      cross-resistance mechanisms. Here, metal contaminated mine soil treated with
      organic wastes was screened for the presence of mobile genetic elements (MGEs).
      The occurrence of conjugative IncP-1 and mobilizable IncQ plasmids, as well as of
      class 1 integrons, was confirmed by PCR and Southern blot hybridization,
      suggesting that bacteria from these soils have gene-mobilizing capacity with
      implications for the dissemination of resistance factors. Moreover, exogenous
      isolation of MGEs from the soil bacterial community was attempted under
      antibiotic selection pressure by using Escherichia coli as recipient. Seventeen
      putative transconjugants were identified based on increased antibiotic
      resistance. Metabolic traits and metal resistance of putative transconjugants
      were investigated, and whole genome sequencing was carried out for two of them.
      Most putative transconjugants displayed a multi-resistant phenotype for a broad
      spectrum of antibiotics. They also displayed changes regarding the ability to
      metabolise different carbon sources, RNA: DNA ratio, growth rate and biofilm
      formation. Genome sequencing of putative transconjugants failed to detect genes
      acquired by horizontal gene transfer, but instead revealed a number of nonsense
      mutations, including in ubiH, whose inactivation was linked to the observed
      resistance to aminoglycosides. Our results confirm that mine soils contain MGEs
      encoding antibiotic resistance. Moreover, they point out the role of spontaneous
      mutations in achieving low-level antibiotic resistance in a short time, which was
      associated with a trade-off in the capability to metabolise specific carbon
      sources.

PMID- 29207351
TI  - Enhancing the efficiency of zero valent iron by electrolysis: Performance and
      reaction mechanism.
AB  - Electrolysis was applied to enhance the efficiency of micron-size zero valent
      iron (mFe0) and thereby promote p-nitrophenol (PNP) removal. The rate of PNP
      removal by mFe0 with electrolysis was determined in cylindrical electrolysis
      reactor that employed annular aluminum plate cathode as a function of
      experimental factors, including initial pH, mFe0 dosage and current density. The
      rate constants of PNP removal by Ele-mFe0 were 1.72-144.50-fold greater than
      those by pristine mFe0 under various tested conditions. The electrolysis-induced
      improvement could be primarily ascribed to stimulated mFe0 corrosion, as
      evidenced by Fe2+ release. The application of electrolysis could extend the
      working pH range of mFe0 from 3.0 to 6.0 to 3.0-10.0 for PNP removal.
      Additionally, intermediates analysis and scavengers experiments unraveled the
      reduction capacity of mFe0 was accelerated in the presence of electrolysis
      instead of oxidation. Moreover, the electrolysis effect could also delay
      passivation of mFe0 under acidic condition, as evidenced by SEM-EDS, XRD, and XPS
      analysis after long-term operation. This is mainly due to increased
      electromigration meaning that iron corrosion products (iron hydroxides and
      oxides) are not primarily formed in the vicinity of the mFe0 or at its surface.
      In the presence of electrolysis, the effect of electric field significantly
      promoted the efficiency of electromigration, thereby enhanced mFe0 corrosion and
      eventually accelerated the PNP removal rates.

PMID- 29207352
TI  - Ecosystem effects and the management of petroleum-contaminated soils on
      subantarctic islands.
AB  - Human activity in the Polar Regions has resulted in petroleum contamination of
      soils. In this context, subantarctic islands are a unique management challenge
      for climatic, biological and logistical reasons. In this review we identify the
      main abiotic factors affecting petroleum-contaminated soils in the subantarctic
      environment, the primary effects of such contamination on biota, and lessons
      learned with regards to remediation techniques in this region. The sensitivity of
      biota to contamination depends on organism life stage, on soil properties, and on
      the degree of contaminant weathering. Initial studies using species endemic to
      subantarctic islands suggest that for fresh diesel fuel, sensitivities may range
      between 103 and 20 000 mg total petroleum hydrocarbons (TPH) kg -1 soil. Diesel
      that has undergone a short period of weathering is generally more toxic, with
      sensitivities ranging between 52 and 13 000 mg TPH kg-1 soil for an earthworm and
      a grass respectively (based on EC20 and IC50 values). A sufficient body of data
      from which to develop remediation targets for existing spills in the region does
      not yet exist for the region, but there has been a recent increase in research
      attention to address this data gap. A range of remediation methods have also now
      been trialled, and techniques such as in-ground aeration and nutrient addition
      have achieved some success. Passive management techniques such as permeable
      reactive barriers and phytoremediation are in preliminary stages of investigation
      for the region and show promise, not least because they cause less collateral
      disturbance than other methods.

PMID- 29207353
TI  - Predicting acute toxicity of traditional Chinese medicine wastewater using UV
      absorption and volatile fatty acids as surrogates.
AB  - In this study, the applicability of UV absorbance at 254 nm (UV254) and volatile
      fatty acids (VFAs) to serve as reliable surrogates to predict acute toxicity of
      traditional Chinese medicine (TCM) wastewater was investigated. The medicine
      residues and VFAs were identified as main components of the TCM wastewater, and
      their individual and joint toxicity assays were operated with luminescent
      bacteria. The median effective concentration (EC50) values of medicine residues
      and VFAs were in the range of 26.46-165.55 mg/L and 11.45-20.58 g/L,
      respectively. The joint toxicity action modes of medicine residues, VFAs and
      medicine residues-VFAs were identified as additive, additive and synergistic
      respectively. UV254 and VFAs showed better correlations with acute toxicity
      according to the correlation analysis, compared with other conventional
      parameters. The regression model was a good fit for toxic unit (TU50) as a
      function of UV254 and VFAs according to the stepwise regression method (adjusted
      R2 = 0.836). Validation of the model to the pilot-scale samples provided
      satisfactory prediction results in the influent and hydrolysis acidification
      effluent samples tests, but for EGSB effluent and final effluent samples, the
      model needed further optimization. Surrogates prediction using UV254 and VFAs
      provided a valuable and cost-saving tool for rapid or on-line monitoring of acute
      toxicity of TCM wastewater.

PMID- 29207354
TI  - Biomonitoring chromium III or VI soluble pollution by moss chlorophyll
      fluorescence.
AB  - We systematically compared the impacts of four Cr salts (chromic chloride,
      chromic nitrate, potassium chromate and potassium bichromate) on physiological
      parameters and chlorophyll fluorescence in indigenous moss Taxiphyllum
      taxirameum. Among the four Cr salts, K2Cr2O7 treatment resulted in the most
      significant decrease in photosynthetic efficiency and antioxidant enzymes,
      increase in reactive oxygen species (ROS), and obvious cell death. Different form
      the higher plants, although hexavalent Cr(VI) salt treatments resulted in higher
      accumulation levels of Cr and were more toxic than Cr(III) salts, Cr(III) also
      induced significant changes in moss physiological parameters and chlorophyll
      fluorescence. Our results showed that Cr(III) and Cr(VI) could be monitored
      distinguishably according to the non-photochemical quenching (NPQ) fluorescence
      of sporadic purple and sporadic lavender images respectively. Then, the valence
      states and concentrations of Cr contaminations could be evaluated according to
      the image of maximum efficiency of PSII photochemistry (Fv/Fm) and the quantum
      yield of PSII electron transport (PhiPSII). Therefore, this study provides new
      ideas of moss's sensibility to Cr(III) and a new method to monitor Chromium
      contaminations rapidly and non-invasively in water.

PMID- 29207356
TI  - Quantification and characterization of chemically-and thermally-labile and
      recalcitrant biochar fractions.
AB  - The C:N ratios of biochar labile fractions is important for assessing biochar
      stability and N cycling in soil. Here we compare chemically and thermally labile
      fractions for nine biochars produced from five biomass feedstocks using four
      production techniques. Biochar fractionation methods included proximate analysis,
      hot water extraction, acid and base extractions (0.05 M, 0.5 M, 1 M, 2 M, 3 M,
      and 6 M of either H2SO4 or NaOH), and oxidation with 15% H2O2 and 0.33 M KMnO4
      (pH 7.2). Results show chemical addition reactions cause underestimation of mass
      of the labile fraction for chemical extraction and oxidation procedures but not
      the thermal procedure. Estimates of C and N in labile and recalcitrant fractions
      were not adversely affected by addition reactions, because solvents were
      independent of C or N. Results indicate that herbaceous biochars may be a source
      of N fertility while hardwood biochars may immobilize N during the first few
      years after biochar application to soils.

PMID- 29207355
TI  - Environmental pollution and health hazards from distillery wastewater and
      treatment approaches to combat the environmental threats: A review.
AB  - Distillery industries are the key contributor to the world's economy, but these
      are also one of the major sources of environmental pollution due to the discharge
      of a huge volume of dark colored wastewater. This dark colored wastewater
      contains very high biological oxygen demand, chemical oxygen demand, total
      solids, sulfate, phosphate, phenolics and various toxic metals. Distillery
      wastewater also contains a mixture of organic and inorganic pollutants such as
      melanoidins, di-n-octyl phthalate, di-butyl phthalate, benzenepropanoic acid and
      2-hydroxysocaproic acid and toxic metals, which are well reported as genotoxic,
      carcinogenic, mutagenic and endocrine disrupting in nature. In aquatic resources,
      it causes serious environmental problems by reducing the penetration power of
      sunlight, photosynthetic activities and dissolved oxygen content. On other hand,
      in agricultural land, it causes inhibition of seed germination and depletion of
      vegetation by reducing the soil alkalinity and manganese availability, if
      discharged without adequate treatment. Thus, this review article provides a
      comprehensive knowledge on the distillery wastewater pollutants, various
      techniques used for their analysis as well as its toxicological effects on
      environments, human and animal health. In addition, various physico-chemicals,
      biological as well as emerging treatment methods have been also discussed for the
      protection of environment, human and animal health.

PMID- 29207357
TI  - Asbestos containing materials detection and classification by the use of
      hyperspectral imaging.
AB  - In this work, hyperspectral imaging in the short wave infrared range (SWIR: 1000
      2500nm) coupled with chemometric techniques was evaluated as an analytical tool
      to detect and classify different asbestos minerals, such as amosite
      ((Fe2+)2(Fe2+,Mg)5Si8O22(OH)2)), crocidolite (Na2(Mg,Fe)6Si8O22(OH)2) and
      chrysotile (Mg3(Si2O5)(OH)4), contained in cement matrices. Principal Component
      Analysis (PCA) was used for data exploration and Soft Independent Modeling of
      Class Analogies (SIMCA) for sample classification. The classification model was
      built using spectral characteristics of reference asbestos samples and then
      applied to the asbestos containing materials. Results showed that identification
      and classification of amosite, crocidolite and chrysotile was obtained based on
      their different spectral signatures, mainly related to absorptions detected in
      the hydroxyl combination bands, such as Mg-OH (2300nm) and Fe-OH (from 2280 to
      2343nm). The developed SIMCA model showed very good specificity and sensitivity
      values (from 0.89 to 1.00). The correctness of classification results was
      confirmed by stereomicroscopic investigations, based on different color,
      morphological and morphometrical characteristics of asbestos minerals, and by
      micro X-ray fluorescence maps, through iron (Fe) and magnesium (Mg) distribution
      assessment on asbestos fibers. The developed innovative approach could represent
      an important step forward to detect asbestos in building materials and demolition
      waste.

PMID- 29207358
TI  - Sequence length dependence in arginine/phenylalanine oligopeptides: Implications
      for self-assembly and cytotoxicity.
AB  - We present a detailed study on the self-assembly and cytotoxicity of arginine
      rich fragments with general form [RF]n (n=1-5). These highly simplified
      sequences, containing only two l-amino acids, provide suitable models for
      exploring both structure and cytotoxicity features of arginine-based
      oligopeptides. The organization of the sequences is revealed over a range of
      length scales, from the nanometer range down to the level of molecular packing,
      and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is
      investigated. We found that the polymorphism is dependent on peptide length, with
      a progressive increase in crystalline ordering upon increasing the number of [RF]
      pairs along the backbone. A dependence on length was also found for other
      observables, including critical aggregation concentrations, formation of chiral
      assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter
      peptides self-assemble into fractal-like aggregates, clear fibrillogenic
      capabilities are identified for longer sequences with octameric and decameric
      chains exhibiting crystalline phases organized into cross-beta structures. Cell
      viability assays revealed dose-dependent cytotoxicity profiles with very similar
      behavior for both glioma and macrophage cell lines, which has been interpreted as
      evidence for a nonspecific mechanism involved in toxicity. We propose that
      structural organization of [RF]n peptides plays a paramount role regarding
      toxicity due to strong increase of local charge density induced by self
      assemblies rich in cationic groups when interacting with cell membranes.

PMID- 29207359
TI  - Telbivudine attenuates UUO-induced renal fibrosis via TGF-beta/Smad and NF-kappaB
      signaling.
AB  - Renal fibrosis yields decreased renal function and is a potent contributor to
      chronic kidney disease (CKD). Telbivudine (LdT) is an anti-hepatitis B virus
      (HBV) drug that has been found to steadily improve renal function, but the
      mechanism of drug action is unclear. One explanation is that LdT impacts
      inflammatory or fibrotic pathways. In this study, we investigated renal
      protection by LdT in a rat model of unilateral ureteral obstruction (UUO). UUO
      rats received oral gavage of LdT (1, 1.5, or 2g/kg/day) for 5weeks. Kidney
      tissues were examined histopathologically with hematoxylin and eosin and Masson's
      trichrome stain. To assess proliferation of myofibroblasts and matrix
      accumulation, alpha-smooth muscle actin (alpha-sma) and collagen type I and III
      were detected. Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha were
      evaluated as a measure of proinflammatory cytokines. Transforming growth factor
      (TGF)-beta and nuclear factor-kappaB (NF-kappaB) were considered the canonical
      signaling components in our investigation of the underlying mechanism of LdT
      action. Histopathology results indicated that LdT ameliorates renal injury and
      matrix accumulation. Expression of alpha-sma and collagen I/III as well as key
      fibrotic signaling factors in the TGF-beta/Smad pathway were downregulated. In
      addition, LdT suppressed the release of IL-1 and TNF-alpha and decreased the
      expression of NF-kappaB by inhibiting toll-like receptor 4. Taken together, these
      findings indicate that LdT can attenuate renal fibrosis and inflammation via TGF
      beta/Smad and NF-kappaB pathways in UUO.

PMID- 29207360
TI  - Oridonin protects against the inflammatory response in diabetic nephropathy by
      inhibiting the TLR4/p38-MAPK and TLR4/NF-kappaB signaling pathways.
AB  - Inflammation plays a pivotal role in the development and progression of diabetic
      nephropathy (DN). Oridonin (Ori), a component isolated from Rabdosia rubescens,
      possesses remarkable anti-inflammatory, immunoregulatory and antitumor
      properties. However, the renoprotective effects of Ori and the underlying
      molecular mechanisms have not been explored in DN. In this study, we aimed to
      investigate the protective effects and potential mechanisms responsible for the
      anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in
      vitro. Our results showed that Ori significantly attenuated diabetes-induced
      renal injury and markedly decreased urinary protein excretion levels, serum
      creatinine concentrations and blood urea nitrogen concentrations in rats. Ori
      also significantly alleviated infiltration of inflammatory cells (cluster of
      differentiation (CD)68) in kidney tissues and reduced the levels of pro
      inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), IL-1beta and monocyte chemotactic protein 1 (MCP-1), both
      in vivo and in vitro. TLR4 is a principal mediator of innate immune and
      inflammatory responses and participates in the development of DN. Our molecular
      studies indicated that Ori administration significantly down-regulated TLR4
      overexpression in DN. Additional studies were conducted to investigate the effect
      of Ori on the p38-mitogen-activated protein kinase (p38-MAPK) and nuclear factor
      (NF)-kappaB pathways. The results showed that Ori inhibited IkappaBalpha, p65,
      and p38 phosphorylation, as well as NF-kappaB DNA-binding activity. In
      conclusion, these results demonstrated that Ori exerts protective effects in
      diabetes-induced renal injury in vivo and in vitro. These effects may be ascribed
      to its anti-inflammatory and modulatory effects on the TLR4/p38-MAPK and TLR4/NF
      kappaB signaling pathways.

PMID- 29207361
TI  - Patient Factors But Not the Use of Novel Anticoagulants or Warfarin Are
      Associated With Internal Jugular Vein Access-Site Hematoma After Right Heart
      Catheterization.
AB  - INTRODUCTION: Right heart catheterization (RHC) is routinely performed to assess
      hemodynamics. Generally, anticoagulants are held prior to the procedure. At our
      center, anticoagulants are continued and ultrasound guidance is always used for
      internal jugular vein access. A micropuncture access kit is used to place a 5 or
      6 Fr sheath using the modified Seldinger technique. Manual compression is applied
      for 10-15 min and the patient is observed for at least 2 hours after the
      procedure. In a retrospective analysis, we investigated the risk of bleeding
      complications associated with RHC via the internal jugular vein in patients with
      and without full anticoagulation. METHODS AND RESULTS: Our catheterization
      laboratory database was searched for adult patients who underwent RHC by a single
      operator between January 2012 and December 2015. A total of 571 patients were
      included in the analysis. Baseline characteristics, labs, relevant invasive
      hemodynamics, co-morbid conditions, and incidence of access-site hematoma are
      presented. Multivariable binary logistic regression was performed using IBM SPSS
      v. 23.0 software. Statistically significant associations with access-site
      hematoma were observed with body mass index (P=.02; 95% confidence interval [CI],
      1.0-1.1), right atrial pressure (P=.03; 95% CI, 0.7-0.9), and dialysis dependence
      (P<.01; 95% CI, 0.1-0.6). There was no association of access-site hematoma with
      the use of anticoagulants (P>.99). CONCLUSION: The incidence of internal jugular
      vein access-site hematoma is small when using careful access techniques for RHC
      even with the continued use of novel oral anticoagulants and warfarin. Patient
      characteristics and co-morbid conditions are related to bleeding complications.

PMID- 29207362
TI  - Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: Indications,
      Technical Aspects, and Clinical Outcomes.
AB  - Hypertrophic cardiomyopathy is the most common genetically transmitted heart
      disease. Around two-thirds of patients develop symptoms caused by the dynamic
      left ventricular outflow tract obstruction, either at rest or during effort. For
      patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain
      symptomatic despite optimal medical treatment, septal reduction is a valuable
      therapeutic strategy. While surgical myomectomy was considered the gold standard
      until the end of the 1990s, alcohol septal ablation (ASA) has gained rapid
      popularity and acceptance, especially in Europe. In this review, we describe
      indications and contraindications to ASA, along with technical considerations
      related to the procedure. Particular emphasis is put on adjunctive imaging
      modalities required for proper patient selection (echocardiography, magnetic
      resonance imaging) and procedure safety (echocardiography). Next, we describe
      postprocedural care and potential procedural complications. Finally, a review of
      the recent literature describing the long-term results of ASA is presented. In
      short, when performed by an experienced team, ASA has a high success rate and low
      complication rate. The procedure provides symptom relief and grants patients
      similar longevity to that of the general population.

PMID- 29207363
TI  - Improvement in Aortic Valve Area in Patients With Aortic Stenosis Through Use of
      a New "Hourglass-Shaped" Valvuloplasty Balloon.
AB  - OBJECTIVES: The study aim was to assess the effect of hourglass-shaped V8 and
      TAV8 balloons (InterValve, Inc) on aortic valve area (AVA) and other outcomes in
      patients with severe aortic stenosis undergoing balloon aortic valvuloplasty
      (BAV). BAV has re-emerged with transcatheter therapy. Cylindrical balloons have
      been the device of choice despite limitations. The hourglass-shaped balloons,
      with shorter, broader segments separated by a narrowed waist, permit enhanced
      fixation and better leaflet opening without annular or sinotubular compromise.
      METHODS: We compared outcomes of InterValve balloon use in patients undergoing
      BAV with outcomes of cylindrical balloon use in patients from a BAV database.
      Patients were propensity matched by age, gender, baseline AVA, left ventricular
      ejection fraction, and Society of Thoracic Surgeons mortality risk score.
      Endpoints included change in AVA and aortic insufficiency (AI) by
      echocardiography, new permanent pacemaker (PPM) implantation, and major adverse
      events (ie, procedural death, emergency surgery, or stroke). RESULTS: Forty
      InterValve balloon patients were matched with 40 cylindrical balloon patients.
      Postprocedure change in AVA trended strongly in favor of InterValve balloon
      patients (0.29 +/- 0.17 cm2 vs 0.22 +/- 0.15 cm2; P=.06). Maximum balloon sizes
      were significantly smaller for InterValve balloon patients. Worsened AI occurred
      less frequently with InterValve balloons. There was no difference in
      postprocedure PPM implantations or major adverse events. CONCLUSIONS: Use of the
      hourglass-shaped balloons provided larger AVA, as compared with use of
      cylindrical balloons. Use of the novel balloons was not associated with an
      increase in AI, PPM, or major adverse events.

PMID- 29207364
TI  - Transpedal Access for the Management of Complex Peripheral Artery Disease.
AB  - OBJECTIVES: To evaluate the safety and efficacy of transpedal access for the
      management of complex peripheral artery disease (PAD). INTRODUCTION: Critical
      limb ischemia is associated with high risk of limb loss, as well as
      cardiovascular and all-cause mortality. Transpedal access is a novel,
      increasingly utilized technique for the management of complex PAD. METHODS: We
      performed a literature search using PubMed from January 2003 to December 2016.
      Published studies on transpedal access were studied. We evaluated patient sample
      demographics, procedure indications, access and target vessel, procedural
      characteristics, outcomes, and complications. RESULTS: Ten studies and 881
      patients were included in our study. The indication for transpedal access was
      critical limb ischemia in 68.4% and severe claudication in 29.5%. A chronic total
      occlusion was present in 93.7% (average occlusion length, 206 mm). Access was
      achieved by ultrasound in 57.1% and by fluoroscopy in 35.7%. The anterior tibial
      or dorsalis pedis were accessed in 54.7% and the posterior tibial in 28.0%. The
      angiographic procedural success rate was 92.6%. The most commonly reported
      complication was dissection (7.49%), followed by perforation (1.36%) and
      embolization (1.25%). CONCLUSION: Based on the results of this systematic review,
      transpedal access appears to be a safe and effective technique for complex PAD.

PMID- 29207365
TI  - Thirty-Day Outcomes in 100 Consecutive Patients Undergoing Transfemoral Aortic
      Valve Replacement With the Portico Valve on an All-Comer Basis.
AB  - OBJECTIVES: Transcatheter heart valves such as the self-expandable Portico valve
      (St. Jude Medical) are being developed to overcome limitations of first
      generation devices. Since clinical experience with this valve is still limited in
      a real-world setting, we investigated its use on an all-comer basis. METHODS:
      Between October 2015 and October 2016, a total of 100 consecutive patients
      assessed for transcatheter aortic valve replacement (TAVR) and found suitable for
      the Portico valve were included. The primary endpoint was 30-day all-cause
      mortality. Secondary endpoints included immediate postprocedural survival,
      complications according to Valve Academic Research Consortium (VARC)-2 criteria,
      and echocardiographic findings. RESULTS: All 100 participants received a Portico
      valve; the patient group included 56 women (56%) and 44 men (44%) with mean age
      of 81.7 +/- 5.1 years. Mean EuroScore II and STS scores were 6.2 +/- 8.6 and 5.2
      +/- 6.1, respectively. Immediate postprocedural survival rate was 99%. The 30-day
      mortality rate (6%) was comparable with earlier studies performed in selected
      patients. Complications included major stroke (2%), minor stroke (2%), major
      vascular complication (2%), minor vascular complication (4%), cardiac tamponade
      (1%), major bleeding (3%), conversion into open surgery (1%), and pacemaker
      implantation (19.5%). Maximal and mean echocardiographic gradients were reduced
      from 66 mm Hg (range, 21-141 mm Hg) to 15 mm Hg (range, 4-41 mm Hg) (P<.001) and
      from 44 mm Hg (range, 12-84 mm Hg) to 8 mm Hg (range, 2-25 mm Hg) (P<.001),
      respectively. A low rate of more-than-mild paravalvular leak was observed (4.4%).
      CONCLUSIONS: Our immediate and 30-day post-TAVR results support favorable
      survival comparable to other studies, and significant clinical improvement with
      the Portico valve in non-selected patients in a real-world setting, with short
      term complications being uncommon.

PMID- 29207366
TI  - Differences in Approaches and Outcomes of Defibrillator Lead Implants Between
      High-Volume and Low-Volume Operators: Results From the Pacemaker and Implantable
      Defibrillator Leads Survival Study ("PAIDLESS").
AB  - OBJECTIVES: The purpose of this study was to investigate the relationship between
      operator volume and implantable defibrillator lead failure and patient mortality
      at a single large implanting center. METHODS: This study analyzed the differences
      between high-volume and low-volume defibrillator implanters in the Pacemaker and
      Implantable Defibrillator Lead Survival Study ("PAIDLESS") between February 1,
      1996 and December 31, 2011 at NYU Winthrop Hospital. "High-volume" was defined as
      performing >=500 implants over the study period, while "low-volume" was defined
      as performing <500 implants. Comparisons between the procedure volume groups were
      performed using Fisher's Exact test, Wilcoxon rank-sum test, and Kaplan-Meier
      analysis as appropriate. RESULTS: Eight operators participated in the study, four
      of whom were high-volume operators. Of 3801 patients, a total of 3149 (83%) were
      operated upon by high-volume operators. Low-volume operators implanted fewer
      recalled leads (12% vs 42%; P<.001) and more often obtained venous access through
      the cephalic vein cutdown approach (63% vs 38%; P<.001) than high-volume
      operators. Kaplan-Meier analysis revealed shorter time to lead failure in the low
      volume group (P=.02). Time to mortality was not significantly different between
      the high-volume and low-volume groups (P=.18). When adjusted for lead recall
      status, patients of high-volume operators were 43% less likely to experience lead
      failure compared to patients of low-volume operators. CONCLUSIONS: High-volume
      defibrillator implanters selected a higher percentage of recalled leads, but
      their patients were less likely to encounter lead failure when adjusted for lead
      recall status compared to low-volume operators.

PMID- 29207367
TI  - Subadventitial Advancement of a Mother-and-Child Catheter to Allow Successful
      Recanalization of a Complex In-Stent Chronic Total Occlusion: Testing the
      Resistance of the Adventitia.
AB  - In-stent chronic total occlusion (CTO) represents a challenging lesion subset for
      percutaneous coronary intervention (PCI), and although a true-to-true lumen
      crossing is the first-line strategy, a subadventitial approach may become
      necessary. Here we describe a case of successful in-stent right coronary artery
      CTO-PCI performed with subadventitial crossing, crushing of the occluded stents,
      and advancement of a mother-and-child catheter to the distal right coronary
      artery through the subadventitial space to allow stent delivery. The use of
      intracoronary imaging in this setting proved crucial to confirm adequate
      apposition of the newly implanted stents and optimal crushing of the occluded
      stents.

PMID- 29207368
TI  - The Reverse T-Stenting and Small Protrusion Technique: A Novel Technique for
      Coronary Bifurcation Lesions.
AB  - Bifurcation lesions may be encountered in approximately 15%-20% of percutaneous
      coronary interventions. A 2-stent approach is required in up to 30% of these
      procedures. We describe a novel technique based on a modification of TAP
      stenting, suitable for procedures where a 2-stent strategy is predetermined.

PMID- 29207369
TI  - Young Athlete With Complex Aneurysmal Coronary Stenosis.
AB  - Kawasaki disease is an acute vasculitis that occurs predominantly in infants and
      children younger than 5 years old. If undiagnosed and untreated, the risk of
      developing coronary artery aneurysms increases to about 20%. In patients who
      present with angina and are found to have coronary artery aneurysm on imaging and
      angiography, Kawasaki disease should be considered as one of the leading
      diagnoses.

PMID- 29207370
TI  - A Bleeding Heart: Coronary-Cameral Fistula After Septal Myomectomy.
AB  - Coronary-cameral fistulas are relatively rare communications arising within the
      coronary vasculature entering into one of the four cardiac chambers. This case
      highlights a striking angiographic example of coronary-cameral fistula occurring
      after septal myomectomy, a complication occurring somewhat frequently with
      typical spontaneous resolution.

PMID- 29207371
TI  - Caught in Time: When IVC Filters Save Lives.
AB  - Inferior vena cava filters are indicated in patients with venous thromboembolic
      disease in whom anticoagulation is a contraindication. This case highlights the
      importance of inferior vena cava filter placement in patients with extensive
      proximal deep vein thromboses in order to prevent massive pulmonary emboli,
      possibly associated with sudden cardiac death.

PMID- 29207372
TI  - Catheter-Induced Coronary Spasm: Serious But Preventable.
AB  - While catheter-induced spasm is considered to be rare, it needs to be ruled out
      (especially in cases of left main stenosis) to avoid unnecessary
      revascularization. We present a patient where the underlying tendency for
      coronary spasm was so high, the severe spasm was possibly the underlying cause of
      a prior cardiac arrest episode.

PMID- 29207373
TI  - A Novel, Simple, and Safe Technique for Retrieving a Crushed Stent From the
      Coronary Artery: Balloon-Assisted Stent Retraction.
AB  - Various percutaneous methods have been described for the retrieval of damaged
      stents; however, these methods can be complex and carry a risk of stent
      embolization or vascular damage. We present a simple and safe technique using a
      compliant balloon for stent retrieval.

PMID- 29207374
TI  - Age-related gene expression changes, and transcriptome wide association study of
      physical and cognitive aging traits, in the Lothian Birth Cohort 1936.
AB  - Gene expression is influenced by both genetic variants and the environment. As
      individuals age, changes in gene expression may be associated with decline in
      physical and cognitive abilities. We measured transcriptome-wide expression
      levels in lymphoblastoid cell lines derived from members of the Lothian Birth
      Cohort 1936 at mean ages 70 and 76 years. Changes in gene expression levels were
      identified for 1,741 transcripts in 434 individuals. Gene Ontology enrichment
      analysis indicated an enrichment of biological processes involved in the immune
      system. Transcriptome-wide association analysis was performed for eleven
      cognitive, fitness, and biomedical aging-related traits at age 70 years (N=665 to
      781) and with mortality. Transcripts for genes (F2RL3, EMILIN1 and CDC42BPA)
      previously identified as being differentially methylated or expressed in smoking
      or smoking-related cancers were overexpressed in smokers compared to non-smokers
      and the expression of transcripts for genes (HERPUD1, GAB2, FAM167A and GLS)
      previously associated with stress response, autoimmune disease and cancer were
      associated with telomere length. No associations between expression levels and
      other traits, or mortality were identified.

PMID- 29207375
TI  - Sexually dimorphic effects of dietary sugar on lifespan, feeding and starvation
      resistance in Drosophila.
AB  - Lifespan and health in older age are strongly influenced by diet. Feeding
      Drosophila melanogaster diets high in sugar has increasingly been used as an
      experimental model to understand the physiological effects of unhealthy,
      contemporary human diets. Several metabolic parameters and physiological
      responses to nutrition are known to be dependent on the sex of the animal.
      However, sexual dimorphism in the responses to high-sugar diets in fruit flies
      has not been examined. Here we show that a high-sugar diet in Drosophila
      melanogaster elicits sexually dimorphic effects on feeding behaviour, starvation
      resistance and lifespan. Females feed less on such diets, while males feed more,
      and these feeding responses may have secondary consequences. Females, more than
      males, gain the ability to resist periods of starvation from high-sugar diets,
      indicating that the female response to excess sugar may be geared towards
      surviving food shortages in early life. At the same time, female lifespan is more
      susceptible to the detrimental effects of high sugar diets. Our study reveals
      differences between Drosophila sexes in their responses to sugar-rich diets,
      indicating the fruit fly could be used as a model to understand the sexually
      dimorphic features of human metabolic health.

PMID- 29207376
TI  - The fat regulator neuropeptide Y and caloric restriction.

PMID- 29207377
TI  - Polymorphisms in Nonamelogenin Enamel Matrix Genes Are Associated with Dental
      Fluorosis.
AB  - The aim of this study was to evaluate whether genetic polymorphisms in AMELX,
      AMBN, ENAM, TFIP11, and TUFT1 genes are associated with dental fluorosis (DF). A
      total of 1,017 children from 2 Brazilian cohorts were evaluated. These
      populations lived in cities with fluoridation of public water supplies. DF was
      assessed in erupted permanent teeth using the modified Dean index. The
      polymorphisms rs946252, rs12640848, rs4694075, rs5997096, and rs4970957 were
      analyzed by real-time PCR from genomic DNA. Associations between DF, genotype,
      and allele distribution were evaluated using the chi2 test, with an alpha of 5%.
      The polymorphisms rs4694075, rs5997096, and rs4970957 in AMBN, TFIP11, and TUFT1
      were associated with DF (p < 0.05). In conclusion, enamel matrix genes are
      associated with DF.

PMID- 29207378
TI  - Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish
      Patients.
AB  - A large cohort of hepatocellular carcinoma (HCC) patients from several
      collaborating Turkish institutions were examined for the tumor parameters of
      maximum diameter (MTD), portal vein thrombosis (PVT), and alpha-fetoprotein (AFP)
      levels. A relationship was found between MTD and blood platelet levels. Patients
      with large >=5 cm tumors who had normal platelet levels had significantly larger
      tumors, higher percent of PVT, and significantly lower blood total bilirubin and
      liver cirrhosis than similar >=5 cm tumor patients having thrombocytopenia. A
      comparison of patients with and without PVT showed significantly larger tumors,
      greater multifocality, blood AFP, and C-reactive protein levels, and,
      interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of
      the total cohort had AFP levels <=100 IU/mL (and 42.1% had values <=20 IU/mL).
      These patients had significantly smaller tumors, less tumor multifocality and
      percent PVT, lower total bilirubin, and less cirrhosis. There was considerable
      geographic heterogeneity within Turkey in the patterns of HCC presentation, with
      areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and
      tumor aggressiveness parameters. Turkish patients thus have distinct patterns of
      presentation, but the biological relationships between MTD and both platelets and
      bilirubin levels are similar to the relationships that have been reported in
      other ethnic patient groups.

PMID- 29207380
TI  - Body Mass Index and Olfactory Fossa Depth in Patients with and without
      Spontaneous Cerebrospinal Fluid Leaks.
AB  - BACKGROUND/AIMS: Spontaneous cerebrospinal fluid (SCSF) leaks are associated with
      a high body mass index (BMI) and an expanded skull base. The purpose of this
      study is to determine if a correlation exists between BMI and olfactory fossa
      depth (OFD) in patients with SCSF leaks and those without. METHODS: This is a
      cross-sectional study evaluating the correlation between OFD and BMI in patients
      with and without SCSF leaks. OFD was measured on computed tomography obtained in
      temporal proximity to the BMI. RESULTS: Patients with SCSF leaks had a deeper
      mean OFD than controls (6.39 vs. 5.46 mm, p = 0.013) and a larger BMI (38.2 vs.
      30.5, p = 0.0003). Pearson correlation was positive between BMI and OFD in women
      from the control group (R = 0.319, n = 93, p = 0.002 on the left; R = 0.313, n =
      93, p = 0.002 on the right) but insignificant in men. CONCLUSIONS: The olfactory
      fossa is deeper and the BMI higher in patients with SCSF leaks than in those
      without. Differences were statistically significant. Higher BMI may predict
      deeper olfactory fossa in women but not in men. These findings suggest expansion
      of weak points in the skull base as precursors to the development of SCSF leaks
      in response to elevated CSF pressures, particularly in women.

PMID- 29207379
TI  - Practical Recommendations of the Obesity Management Task Force of the European
      Association for the Study of Obesity for the Post-Bariatric Surgery Medical
      Management.
AB  - Bariatric surgery is today the most effective long-term therapy for the
      management of patients with severe obesity, and its use is recommended by the
      relevant guidelines of the management of obesity in adults. Bariatric surgery is
      in general safe and effective, but it can cause new clinical problems and is
      associated with specific diagnostic, preventive and therapeutic needs. For
      clinicians, the acquisition of special knowledge and skills is required in order
      to deliver appropriate and effective care to the post-bariatric patient. In the
      present recommendations, the basic notions needed to provide first-level adequate
      medical care to post-bariatric patients are summarised. Basic information about
      nutrition, management of co-morbidities, pregnancy, psychological issues as well
      as weight regain prevention and management is derived from current evidences and
      existing guidelines. A short list of clinical practical recommendations is
      included for each item. It remains clear that referral to a bariatric
      multidisciplinary centre, preferably the one performing the original procedure,
      should be considered in case of more complex clinical situations.

PMID- 29207382
TI  - Incidental Septostomy after Laser Surgery for Twin-Twin Transfusion Syndrome:
      Perinatal Outcomes and Antenatal Management.
AB  - INTRODUCTION: Incidental septostomy, or inadvertent perforation of the twins'
      dividing membranes, can create a functional monoamniotic twin pregnancy. Our aim
      was to describe the perinatal outcomes and antenatal management of patients with
      incidental septostomy after laser surgery for twin-twin transfusion syndrome
      (TTTS). MATERIALS AND METHODS: Monochorionic diamniotic multiple gestations with
      a gestational age (GA) between 16 and 26 weeks that underwent laser surgery from
      March 2006 to December 2015 were studied retrospectively. Perinatal outcomes were
      compared for patients with and without an incidental septostomy. A subgroup
      analysis was performed to evaluate antenatal management. RESULTS: Of 532 TTTS
      patients who underwent laser surgery, incidental septostomy occurred in 34
      (6.4%). Compared to all others, patients with a septostomy had an earlier median
      (range) GA at delivery (30.8 [18.6-37.9] vs. 34.0 [19.3-40.4] weeks, p < 0.0001)
      and lower 30-day survival of at least one twin (85.3 vs. 94.6%, p = 0.0452). We
      found no evidence that inpatient fetal surveillance was protective. DISCUSSION:
      Incidental septostomy in TTTS patients treated via laser surgery appeared to be
      associated with lower GA at delivery and perinatal survival of at least one twin.
      Further study is required to determine the optimal antenatal surveillance
      strategy.

PMID- 29207381
TI  - Alicaforsen, an Antisense Inhibitor of Intercellular Adhesion Molecule-1, in the
      Treatment for Left-Sided Ulcerative Colitis and Ulcerative Proctitis.
AB  - BACKGROUND: Data on the efficacy of intercellular adhesion molecule-1 antisense
      oligonucleotide alicaforsen in ulcerative colitis (UC) is inconsistent. METHODS:
      All patients, who had received at least one dose of alicaforsen, were analyzed
      retrospectively. Alicaforsen's efficacy was assessed in patients treated for left
      sided UC and proctitis by comparing clinical and (if applicable) endoscopic
      disease activity before/after treatment. RESULTS: Twelve patients were treated
      for left-sided UC or proctitis. Eleven patients received a 6-week course of a
      once-daily 240 mg alicaforsen enema formulation. In 1 patient, treatment was
      discontinued, because it was found to be inefficient. Disease activity measured
      by the partial Mayo score and 6-point symptom score was significantly reduced
      after treatment (6.0 vs. 2.4, p = 0.011 and 3.7 vs. 1.4, p = 0.008). Faecal
      calprotectin showed a trend towards reduction (484.4 vs. 179.5 MUg/g, p = 0.063).
      Clinical improvement was achieved in 10 patients (83.3%). In 7 patients, a
      relapse occurred (70%). Median duration of clinical improvement was 18.0 weeks
      (range 1-112). Three patients showed an ongoing improvement of >9 months. No
      adverse events were reported. CONCLUSIONS: A 6-week course of alicaforsen seemed
      to be safe and efficacious in inducing clinical improvement in patients with left
      sided UC and proctitis. Prolonged clinical improvement was observed in many but
      not all patients.

PMID- 29207383
TI  - Thoracic Changes after Full Laser Ablation of the Feeding Artery in Fetuses with
      Bronchopulmonary Sequestration.
AB  - OBJECTIVE: To assess longitudinal intrathoracic changes after fetal laser surgery
      in fetuses with bronchopulmonary sequestration (BPS) with hydrops and/or
      hydrothorax. STUDY DESIGN: The presence of intrafetal fluid effusions, the lung
      mass volume ratio (congenital pulmonary airway malformation volume ratio [CVR]),
      and the observed/expected lung-to-head circumference ratio (O/E-LHR) of both
      lungs were evaluated in a cohort of BPS fetuses with hydrops and/or hydrothorax
      treated with full laser ablation of the feeding artery (FLAFA). The longitudinal
      changes in intrafetal fluid effusions, lung mass volume, and pulmonary growth
      were analyzed by survival and multilevel analysis against days after FLAFA.
      RESULTS: FLAFA was successfully performed in 15 cases at a median gestational age
      of 26.9 weeks. A complete disappearance of the hydrops and hydrothorax was
      observed a median interval of 7.5 and 21 days after the fetal intervention,
      respectively. A progressive decrease in the CVR and an increment in the size of
      both lungs were observed after FLAFA. The O/E-LHR of the lung contralateral and
      ipsilateral to the side of the BPS became normal on average 8 and 10 weeks after
      FLAFA, respectively. CONCLUSION: Fetal laser surgery with FLAFA promotes
      disappearance of all fetal fluid effusions, a lung mass regression sequence, and
      a normalization of pulmonary growth.

PMID- 29207384
TI  - SLC2A1 Tag SNPs in Greek Patients with Diabetic Retinopathy and Nephropathy.
AB  - : Backround: Genetic variants are implicated in the development of diabetic
      retinopathy (DR) and nephropathy (DN). The role of solute carrier family 2
      facilitated glucose transporter member 1 (SLC2A1), also known as glucose
      transporter (GLUT1), on DR and DN remain controversial. OBJECTIVE: Examination of
      the influence of tag SLC2A1 single-nucleotide polymorphisms (SNPs) on the
      development of DR and DN during the course of type 2 diabetes mellitus (T2DM).
      METHODS: A total of 169 patients with DR or DN, 107 uncomplicated T2DM patients,
      and 315 controls were recruited and genotyped for 14 SLC2A1 tag SNPs. SNPs and
      haplotypes were tested for associations with microvascular diabetes'
      complications. RESULTS: rs3768029 TT genotype was associated with a lower risk of
      DR + DN, compared to the CC wild-type (p = 0.0024). Moreover, CT and TT rs841847
      genotypes were associated with a higher risk of DR + DN compared to the CC
      genotype (p = 0.0028). A common haplotype (GGCCCGCATCAAT) was associated with an
      increased risk of DR, DN, DR +/- DN, and DR + DN phenotypes. Mutational loads of
      rs3768029, rs3729548, rs841853, and rs841847 were found to influence the
      development of microvascular complications during the T2DM course. CONCLUSIONS:
      This study provides evidence that SLC2A1 gene variants might be implicated in the
      development of T2DM microvascular complications.

PMID- 29207385
TI  - Real or Perceived: Hyperkalemia Is a Major Deterrent for Renin-Angiotensin
      Aldosterone System Inhibition in Heart Failure.

PMID- 29207386
TI  - Follow-Up of Asymptomatic High-Risk Patients with Normal Cervical Length to
      Predict Recurrence of Preterm Birth.
AB  - BACKGROUND: A midtrimester cervical length (CL) <25 mm is associated with
      spontaneous preterm birth (sPTB). However, as CL >=25 mm is not enough to exclude
      recurrence in high-risk patients, follow-up CL measurement later in pregnancy has
      been proposed. OBJECTIVES: To evaluate whether CL measurement at 26+/-1 weeks in
      asymptomatic high-risk patients improves the prediction of sPTB recurrence.
      METHODS: A retrospective cohort of high-risk women because of previous sPTB was
      analyzed. Patients with a CL >=25 mm at 20+/-1 weeks and subsequent CL
      measurement at 26+/-1 weeks were included. The exclusion criteria were incomplete
      follow-up, any treatment before CL assessments, and medically indicated preterm
      birth. The association and predictive performance of CL at 26+/-1 weeks for sPTB
      was studied. RESULTS: Of 131 patients with a CL measurement at 26+/-1 weeks, 19
      and 4.6% presented sPTB before 37 and 34 weeks, respectively. The rate of sPTB
      before 37 weeks was higher in women with a CL <25 mm (37.5 vs. 16.5%, RR 2.3
      [1.07-4.8], p = 0.045), although the detection rate of CL at 26+/-1 weeks to
      predict sPTB before 37 weeks was 24% (95% CI 10-46%). The performance did not
      improve regardless of the selected cutoff. CONCLUSIONS: In asymptomatic high-risk
      patients, CL <25 mm at 26+/-1 weeks is associated with higher risk of sPTB.
      However, the prediction of recurrence by CL was low and did not improve,
      regardless of the selected cutoff.

PMID- 29207387
TI  - Comparative Effects of Education and Bilingualism on the Onset of Mild Cognitive
      Impairment.
AB  - BACKGROUND: Increasing evidence suggests that life course factors such as
      education and bilingualism may have a protective role against dementia due to
      Alzheimer disease. This study aimed to compare the effects of education and
      bilingualism on the onset of cognitive decline at the stage of mild cognitive
      impairment (MCI). METHODS: A total of 115 patients with MCI evaluated in a
      specialty memory clinic in Hyderabad, India, formed the cohort. MCI was diagnosed
      according to Petersen's criteria following clinical evaluation and brain imaging.
      Age at onset of MCI was compared between bilinguals and monolinguals, and across
      subjects with high and low levels of education, adjusting for possible
      confounding variables. RESULTS: The bilingual MCI patients were found to have a
      clinical onset of cognitive complaints 7.4 years later than monolinguals (65.2
      vs. 58.1 years; p = 0.004), while years of education was not associated with
      delayed onset (1-10 years of education, 59.1 years; 11-15 years of education,
      62.6 years; >15 years of education, 62.2 years; p = 0.426). CONCLUSION: The
      effect of bilingualism is protective against cognitive decline, and lies along a
      continuum from normal to pathological states. In comparison, the role of years of
      education is less robust.

PMID- 29207388
TI  - Resveratrol Does Not Protect from Ischemia-Induced Acute Kidney Injury in an in
      Vivo Rat Model.
AB  - BACKGROUND/AIMS: The natural polyphenol resveratrol (RSV) has been shown to
      ameliorate ischemia/reperfusion (I/R)-induced damage. Therefore, a rat model of
      I/R-induced AKI equipped with intensive monitoring was utilized to examine direct
      renal protection by RSV in vivo. METHODS: AKI was induced by bilateral renal
      clamping (45 min) followed by reperfusion (3 h). Solvent-free RSV was
      continuously infused intravenously (0.056 and 0.28 mg/kg) in a total volume of 7
      ml/kg/h starting from 30 min before renal clamping. At a mean arterial blood
      pressure below 70 mmHg for more than 5 min, bolus injections of 0.5 ml 0.9% NaCl
      solution were administered repetitively (max. 5 ml/kg/h). RESULTS: No differences
      could be found between normoxic control groups with/without RSV. Bilateral renal
      clamping and subsequent reperfusion caused a progressive rise in creatinine,
      cystatin C, and CK, a decrease in cellular ATP content and diuresis. Infusion of
      RSV increased sirtuin 1 expression after ischemia/reperfusion and was associated
      with decreased blood pressure during ischemia and early reperfusion accompanied
      by an increased requirement of bolus injections as well as with increased
      expression of TNFalpha. CONCLUSION: RSV did not exert protective effects on I/R
      induced AKI in the present short-term in vivo rat model. The lack of protection
      is potentially connected to aggravation of blood pressure instability.

PMID- 29207391
TI  - Tooth Extraction Locally Stimulates Proliferation of Multiple Myeloma in a
      Patient with Mandibular Localizations.
AB  - OBJECTIVES: Multiple myeloma (MM) is characterized by the occurrence of
      osteolytic lesions. MM treatment usually involves antiresorptive drugs (mainly
      bisphosphonates). CASE REPORT: A patient with an MM presented osteolytic lesions
      of the mandible. Extraction of teeth 45 and 46 was performed 5 years after the
      diagnosis of periodontitis. Four months later, osteonecrosis of the jaw (ONJ) was
      diagnosed at the extraction site. X-ray showed an extension of osteolytic lesions
      on the right side, close to the extraction site, without modification of the
      lesions on the left side. Two months later, a curettage was performed because of
      a painful bone sequestration. X-ray showed an extension of the osteolytic lesions
      on the right side. RESULTS: Histological analysis found a vascularized
      plasmacytoma of the soft tissues around the ONJ. Analysis of the bone showed
      mixed lesions with osteonecrotic areas and living bone resorbed by active
      osteoclasts surrounding a plasmacytoma. The surface area of the osteolytic foci
      has considerably increased only close to the extraction site. CONCLUSIONS: Tooth
      extraction triggered an ONJ associated with bisphosphonate treatment. However, it
      also seemed to induce a considerable proliferation of plasma cells at the
      extraction site; we hypothesize that it is due to the increase in bone remodeling
      related to the surgical trauma.

PMID- 29207392
TI  - Distinct Roles of Endothelial Dysfunction and Inflammation in Intracranial
      Atherosclerotic Stroke.
AB  - BACKGROUND/AIMS: The aim of the study was to evaluate the differential roles of
      endothelial dysfunction and inflammation in intracranial atherosclerotic stroke
      (ICAS). METHODS: We prospectively recruited 262 patients with acute cerebral
      infarcts caused by ICAS and 75 individuals with no history of stroke as controls.
      Markers of endothelial dysfunction (asymmetric dimethylarginine, ADMA) and
      inflammation (lipoprotein-associated phospholipase A2, Lp-PLA2) were measured.
      Acute ischemic lesions were measured in terms of their size, composition, and
      patterns. Subclinical microangiopathy (degree of leukoaraiosis) and
      macroangiopathy (presence/number of asymptomatic stenoses) were graded in each
      patient. RESULTS: Compared to normal controls, serum levels of ADMA (0.69 +/-
      0.14 vs. 0.47 +/- 0.10, p < 0.001) and Lp-PLA2 (138.1 +/- 116.8 vs. 19.0 +/-
      58.0, p < 0.001) were elevated in patients with ICAS. A high ADMA serum level was
      associated with greater prevalence of preclinical microangiopathy and
      macroangiopathy. Contrastingly, an elevated serum Lp-PLA2 level was associated
      with larger ischemic lesions, a greater number of lesions, and a larger cortical
      pattern. CONCLUSIONS: Endothelial dysfunction and inflammation have distinct
      effects in ICAS patents; endothelial dysfunction is associated with the
      underlying micro- and macro-atherosclerotic burden, whereas inflammation is
      associated with acute infarct volume and pattern.

PMID- 29207393
TI  - How Virtue Was Born.
AB  - This paper summarizes the Opening Lecture of the European Forum Alpbach 2017 in
      Tyrol/Austria (https://www.alpbach.org/de/). It deals with the evolution of
      cooperation throughout the history of life on Earth, and in particular human
      cooperation based on partnership. It emphasizes the role of institutions
      providing incentives for cooperation, and the role of praise and blame in guiding
      our actions. This helps for a better understanding of the social contract, based
      on evolutionary biology and psychology.

PMID- 29207394
TI  - Cumulative Effect of Obesogenic Behaviours on Adiposity in Spanish Children and
      Adolescents.
AB  - OBJECTIVE: Little is known about the cumulative effect of obesogenic behaviours
      on childhood obesity risk. We determined the cumulative effect on BMI z-score,
      waist-to-height ratio (WHtR), overweight and abdominal obesity of four lifestyle
      behaviours that have been linked to obesity. METHODS: In this cross-sectional
      analysis, data were obtained from the EnKid sudy, a representative sample of
      Spanish youth. The study included 1,614 boys and girls aged 5-18 years. Weight,
      height and waist circumference were measured. Physical activity (PA), screen
      time, breakfast consumption and meal frequency were self-reported on structured
      questionnaires. Obesogenic behaviours were defined as <1 h PA/day, >=2 h/day
      screen time, skipping breakfast and <3 meals/day. BMI z-score was computed using
      age- and sex-specific reference values from the World Health Organization (WHO).
      Overweight including obesity was defined as a BMI > 1 SD from the mean of the WHO
      reference population. Abdominal obesity was defined as a WHtR >= 0.5. RESULTS:
      High screen time was the most prominent obesogenic behaviour (49.7%), followed by
      low physical activity (22.4%), low meal frequency (14.4%), and skipping breakfast
      (12.5%). Although 33% of participants were free of all 4 obesogenic behaviours,
      1, 2, and 3 or 4 behaviours were reported by 44.5%, 19.3%, and 5.0%,
      respectively. BMI z-score and WHtR were positively associated (p < 0.001) with
      increasing numbers of concurrent obesogenic behaviours. The odds of presenting
      with obesogenic behaviours were significantly higher in children who were
      overweight (OR 2.68; 95% CI 1.50; 4.80) or had abdominal obesity (OR 2.12; 95% CI
      1.28; 3.52); they reported more than 2 obesogenic behaviours. High maternal and
      parental education was inversely associated (p = 0.004 and p < 0.001,
      respectively) with increasing presence of obesogenic behaviours. Surrogate
      markers of adiposity increased with numbers of concurrent presence of obesogenic
      behaviours. The opposite was true for high maternal and paternal education.

PMID- 29207395
TI  - Adiponectin and Its Receptors Are Differentially Expressed in Human Tissues and
      Cell Lines of Distinct Origin.
AB  - BACKGROUND: Adiponectin is secreted by adipose tissue and exerts high abundance
      and an anti-inflammatory potential. However, only little information exists about
      the expression profiles of adiponectin and its recently identified receptor CDH13
      in non-tumorous human tissues and their association to clinical parameters.
      METHODS: The expression levels of adiponectin and CDH13 were analyzed in heart,
      liver, kidney, spleen, skin, blood vessels, peripheral nerve and bone marrow of
      21 human body donors, in 12 human cell lines, and in purified immune effector
      cell populations of healthy blood donors by immunohistochemistry, Western-blot,
      and semi-quantitative PCR. The obtained results were then correlated to clinical
      parameters, including age, sex and known diseases like cardiovascular and renal
      diseases. RESULTS: Adiponectin expression in renal corpuscles was significantly
      higher in humans with known renal diseases. A coordinated expression of
      adiponectin and CDH13 was observed in the myocard. High levels of adiponectin
      could be detected in the bone marrow, in certain lymphoid tumor cell lines and in
      purified immune effector cell populations of healthy donors, in particular in
      cytotoxic T cells. CONCLUSION: For the first time, the expression profiles of
      adiponectin and CDH13 are analyzed in many human tissues in correlation to each
      other and to clinical parameters.

PMID- 29207396
TI  - Instrumentalization of Eating Improves Weight Loss Maintenance in Obesity.
AB  - AIM: The purpose of this study was to identify psychosocial determinants for
      maintaining weight loss. METHODS: 42 obese individuals who achieved a 12% weight
      loss before entering a 52-week weight maintenance program were interviewed
      qualitatively. Psychosocial factors related to weight loss maintenance were
      identified in two contrasting groups: weight reducers and weight regainers.
      Groups were defined by health-relevant weight maintenance (additional weight loss
      > 3% at week 52, n = 9 versus weight gain > 3%, at week 52, n = 20). RESULTS:
      Weight reducers reported structured meal patterns (p = 0.008), no comfort eating
      (p = 0.016) and less psychosocial stress (p = 0.04) compared to weight regainers.
      The ability to instrumentalize eating behavior emerged as an important factor (p
      = 0.007). Nutritional knowledge, motivation or exercise level did not differ
      between groups (p > 0.05). CONCLUSIONS: Successful weight loss maintenance was
      associated with an interplay between behavioral, affective and contextual
      changes. 'Instrumentalization of eating behavior' seems to be an important
      element in long-term weight maintenance.

PMID- 29207397
TI  - Relationship of Serum Fetuin A with Metabolic and Clinical Parameters in German
      Children and Adolescents with Type 1 Diabetes.
AB  - BACKGROUND AND AIM: The hepatokine fetuin A is upregulated in the metabolic
      syndrome and in type 2 diabetes (T2D), while its role in adolescent type 1
      diabetes (T1D) is unclear. We assessed the relationship between circulating
      fetuin A levels and metabolic control, comorbidities, and complications in
      adolescent T1D patients. METHODS: We studied the relationship between serum
      fetuin A and clinical diabetes-related data from the DPV registry (Diabetes-Pa
      tienten-Verlaufsdokumentation) in 172 adolescent T1D patients with early-onset
      (<5 years) long-standing (>10 years) T1D. Fetuin A levels were further compared
      between adolescent T1D and T2D patients. RESULTS: Serum fetuin A levels in T1D
      patients (mean 0.267 +/- 0.043 g/L) did not correlate with age, diabetes
      duration, gender, body mass index (BMI), glycated hemoglobin, serum lipid levels,
      blood pressure, celiac or thyroid disease, nephropathy, or retinopathy. An
      association of fetuin A levels with insulin requirements was only evident within
      the subgroup of overweight T1D patients (rs = 0.439, p = 0.028, n = 25, BMI >90th
      percentile), disappearing after adjustment for multiple testing. Adolescent T1D
      patients showed distinctly lower fetuin A levels than patients with T2D (p <=
      0.001). CONCLUSION: Overall, we did not observe a clinically relevant association
      of fetuin A levels with surrogate parameters for insulin sensitivity in our
      juvenile T1D cohort. A correlation with insulin requirements was detectable in
      overweight patients only. We hypothesize that multiple factors, such as obesity,
      puberty, inadequate metabolic control, and hepatic steatosis, have to add up
      before a clinically relevant effect of fetuin A on insulin sensitivity becomes
      evident.

PMID- 29207398
TI  - Involvement of N-Methyl-D-Aspartic Acid Receptor and DL-alpha-Amino-3-Hydroxy-5-
      Methyl-4-Isoxazole Propionic Acid Receptor in Ginsenosides Rb1 and Rb3 against
      Oxygen-Glucose Deprivation-Induced Injury in Hippocampal Slices from Rat.
AB  - OBJECTIVE: Ginsenosides, Rb1 and Rb3, are the major protopanaxadiol components of
      ginseng saponin. In the present study, the influences of ginsenosides Rb1 and Rb3
      on N-methyl-D-aspartic acid (NMDA) receptor or DL-alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionic acid (AMPA) receptor-mediated synaptic transmission after
      oxygen-glucose deprivation (OGD) were investigated. METHODS: NMDA receptor
      population spike (NMDA-PS) or AMPA receptor-mediated population spike (AMPA-PS)
      was recorded in the CA1 pyramidal cell layer of rat hippocampal slices by
      electrophysiological techniques. RESULTS: Under normal conditions, ginsenosides
      Rb3 and Rb1 depressed glutamate receptors-mediated synaptic transmission.
      Fourteen min of OGD resulted in a poor recovery amplitude of NMDA-PS or AMPA-PS
      after reoxygenation. Ginsenoside Rb3 significantly delayed the appearance of
      transient recovery of PS during OGD, and improved the recovery amplitudes of NMDA
      PS and AMPA-PS after reoxygenation. However, the similar protective effects of
      ginsenoside Rb1 were observed only on NMDA-PS but not AMPA-PS. CONCLUSION: These
      results suggest that ginsenosides Rb1 and Rb3 have the different inhibitions on
      NMDA and AMPA receptors-mediated response, which may partially explain the
      different protective effects of these agents on ischemic neuronal death.

PMID- 29207404
TI  - Cognitive Development in Pediatric Epilepsy Surgery.
AB  - Epilepsy surgery is a very effective treatment option for children and
      adolescents with drug-resistant structural epilepsy, resulting in seizure freedom
      in the majority of cases. Beyond seizure freedom, the postsurgical stabilization
      or even improvement of cognitive development constitutes a fundamental objective.
      This study aims to address key features of cognitive development in the context
      of pediatric epilepsy surgery. Many surgical candidates present with severe
      developmental delay and cognitive deficits prior to surgery. Recent studies
      support that global cognitive development remains stable after surgery.
      Individual developmental trajectories are determined by the degree of presurgical
      developmental impairment, age at surgery, seizure freedom, antiepileptic drug
      tapering, and other case-specific factors. Compared with adults, children may
      better compensate for temporary postsurgical deficits in circumscribed cognitive
      functions such as memory. Particularly for left-sided temporal resections,
      children present a clear advantage in terms of postsurgical recovery with regard
      to verbal learning compared with adults. In the case of severe presurgical
      developmental impairment, minimal postsurgical improvements are often not
      measurable, although they are evident to patients' families and have a large
      impact on their quality of life. Multicenter studies with a standardized
      assessment protocol and longer follow-up intervals are urgently called for to
      provide deeper insights into the cognitive development after epilepsy surgery, to
      analyze the interaction between different predictors, and to facilitate the
      selection of appropriate candidates as well as the counseling of families.

PMID- 29207405
TI  - [Correction: Glove Disinfection: Knowledge, Experiences and Attitudes of Hygiene
      Team Members and Company Physicians].

PMID- 29207406
TI  - Double-clip counter-traction using a rubber band is a useful and adaptive tool
      for colonic endoscopic submucosal dissection.

PMID- 29207407
TI  - Triple stenting to treat a complete Wirsung-to-jejunum anastomotic leak after
      pancreaticoduodenectomy.

PMID- 29207408
TI  - Joshua P. Klein, MD, PhD, FANA, FASN, FAAN.

PMID- 29207409
TI  - Neuroimaging.

PMID- 29207411
TI  - Magnetic Resonance Spectroscopy as a Biomarker for Chronic Traumatic
      Encephalopathy.

PMID- 29207410
TI  - Functional Networks in Disorders of Consciousness.
AB  - Severe brain injury may cause disruption of neural networks that sustain arousal
      and awareness, the two essential components of consciousness. Despite the
      potentially devastating immediate and long-term consequences, disorders of
      consciousness (DoC) are poorly understood in terms of their underlying
      neurobiology, the relationship between pathophysiology and recovery, and the
      predictors of treatment efficacy. Recent advances in neuroimaging techniques have
      enabled the study of network connectivity, providing great potential to improve
      the clinical care of patients with DoC. Initial discoveries in this field were
      made using positron emission tomography (PET). More recently, functional magnetic
      resonance (fMRI) techniques have added to our understanding of functional network
      dynamics in this population. Both methods have shown that whether at rest or
      performing a goal-oriented task, functional networks essential for processing
      intrinsic thoughts and extrinsic stimuli are disrupted in patients with DoC
      compared with healthy subjects. Atypical connectivity has been well established
      in the default mode network as well as in other cortical and subcortical networks
      that may be required for consciousness. Moreover, the degree of altered
      connectivity may be related to the severity of impaired consciousness, and
      recovery of consciousness has been shown to be associated with restoration of
      connectivity. In this review, we discuss PET and fMRI studies of functional and
      effective connectivity in patients with DoC and suggest how this field can move
      toward clinical application of functional network mapping in the future.

PMID- 29207413
TI  - Advances in Imaging Multiple Sclerosis.

PMID- 29207414
TI  - TSPO-PET Imaging to Assess Cerebral Microglial Activation in Multiple Sclerosis.

PMID- 29207415
TI  - Acute Stroke Multimodal Imaging: Present and Potential Applications toward
      Advancing Care.

PMID- 29207416
TI  - Advances in Neuro-Ophthalmic Imaging.

PMID- 29207417
TI  - Imaging for Epilepsy Surgery.

PMID- 29207418
TI  - Neuroimaging of Brain Tumors: Pseudoprogression, Pseudoresponse, and Delayed
      Effects of Chemotherapy and Radiation.

PMID- 29207419
TI  - Clinical Experience with the Implementation of Accurate Measurement of Blood Loss
      during Cesarean Delivery: Influences on Hemorrhage Recognition and Allogeneic
      Transfusion.
AB  - OBJECTIVE:  This article compares hemorrhage recognition and transfusion using
      accurate, contemporaneous blood loss measurement versus visual estimation during
      cesarean deliveries. STUDY DESIGN:  A retrospective cohort study using visually
      estimated blood loss (traditional, n = 2,025) versus estimates using a mobile
      application that photographs sponges and canisters and calculates their
      hemoglobin content (device, n = 756). RESULTS:  Blood loss > 1,000 mL was
      recognized in 1.9% of traditional visual estimation patients, while measured
      blood loss of > 1,000 mL occurred in 8.2% of device patients (p < 0.0001). In
      both groups, this was accompanied by a greater decrease in transfusion-adjusted
      hemoglobin levels than occurred in patients without hemorrhage (p < 0.0001).
      Despite similar transfusion rates (1.6% in both groups), fewer red cell units
      were given to transfused patients in the device group (1.83 +/- 0.58 versus 2.56
      +/- 1.68 units; p = 0.038). None of the patients in the device group received
      plasma or cryoprecipitate. Seven patients in the traditional group received these
      products (p = 0.088). Device use was associated with shorter hospital stays (4.0
      +/- 2.3 versus 4.4 +/- 2.9 days; p = 0.0006). CONCLUSION:  The device identified
      hemorrhages more frequently than visual estimation. Device-detected hemorrhages
      appeared clinically relevant. Blood product transfusion was reduced possibly due
      to earlier recognition and treatment, although further studies are needed to
      verify the conclusion.

PMID- 29207420
TI  - [Internal Medicine - from Guidelines to "Choosing Wisely"].

PMID- 29207412
TI  - Neuroimaging in Dementia.

PMID- 29207421
TI  - [Management of Lymphedema].

PMID- 29207422
TI  - [Pheochromocytoma - Current Recommendations on Diagnostics, Therapy and Follow
      up].

PMID- 29207423
TI  - [Addiction in Old Age].

PMID- 29207424
TI  - [Current Aspects of Diagnosis and Treatment of Lung Cancer].

PMID- 29207425
TI  - [Update on Uncomplicated Urinary Tract Infections - New Guideline 2017].

PMID- 29207426
TI  - [Management of Delirium in the Intensive Care Unit].

PMID- 29207427
TI  - [2016 ESC Position Paper on Cancer Treatments and Cardiovascular Toxicity].

PMID- 29207428
TI  - [Primary and Secondary Glomerular Diseases - Update 2017].

PMID- 29207429
TI  - [Rheumatoid Arthritis - New Treatment Options].

PMID- 29207430
TI  - [Novel Developments in Autoimmune Liver Diseases].

PMID- 29207431
TI  - [79-Year-Old Male Patient in Reduced General Condition with a Pronounced Cough].

PMID- 29207432
TI  - [Sonography of the Optic Nerve: a New Bedside Tool in Intensive Care?]
AB  - History and clinical findings Here, we present the case history of a 76-year old
      man with out-of-hospital cardiac arrest due to a cardiogenic shock and a
      consecutive no-flow-time of approximately 10 minutes. After 25 minutes of
      resuscitation procedures a spontaneous return of circulation could be
      established. The patient was admitted to our center for emergency coronary
      angiography. After coronary stenting the patient was admitted to our intensive
      care unit and treated in accordance with the guidelines on cardiogenic shock due
      to myocardial infarction. Therapy and course After therapeutic hypothermia and
      subsequent termination of analgosedation a delayed wake-up reaction could be
      remarked. In the laboratory chemistry the initial parameter of neuron-specific
      enolase, a marker for cerebral hypoxia, was increased. Measurement of the optic
      nerve sheath diameter with a maximum diameter of 7 mm indicated an increased
      intracranial pressure. In the subsequent CT scan of the brain signs of hypoxic
      encephalopathy with breakup of grey and white matter differentiation were
      present. Conclusions In case of clinical and/or laboratory-chemical indications
      for hypoxic encephalopathy and/or increased intracranial pressure the bedside
      based sonography examination at the intensive care unit should imply an
      evaluation of the optic nerve in order to initiate early apparative neurological
      diagnostics.

PMID- 29207433
TI  - [From the History of the German Society of Internal Medicine (DGIM) - Part 1: The
      DGIM in the Nazi era].
AB  - 51 years after its founding in 1882, the "Congress for Internal Medicine", 1920
      renamed "German Society for Internal Medicine (DGIM)", fell into heavy water.
      While during the Kaiserreich and the Weimar Republic the medical care for the
      individual patient had never been seriously questioned, the proclaimed "Third
      Reich" brought fundamental changes. The 1164 male and 13 female physicians, who
      had been organized in the DGIM 1933, had to position themselves in the Nazi
      dictatorship. The same applied for the society as a whole.The behavior of the
      German Society of Internal Medicine during the Nazi period is disenchanting. The
      society completely subordinated to the Nazi regime. The scientific program of the
      meetings was oriented to the ideological interests of the regime. Solidarity with
      nazi-persecuted people is only apparent in rare cases. On the contrary, even DGIM
      chairmen were involved in expulsions and NS-medical crimes. Cautious criticism
      was limited to a few areas, such as the "Neue Deutsche Heilkunde" ("New German
      Healing") and the study conditions at the universities. Only individual DGIM
      members developed oppositional behavior on the basis of personal conviction.In
      accordance with the more recent research on the Nazi era, these results both
      clarify and broaden the picture of scientific organizations in general and
      medical societies in particular.

PMID- 29207435
TI  - Iron Pharmacokinetics in Women with Iron Deficiency Anaemia Following A Single
      Oral Dose of a Novel Formulation of Tardyferon (Prolonged Release Ferrous
      Sulphate).

PMID- 29207434
TI  - Role of Endovascular Aortic Repair in the Treatment of Infected Aortic Aneurysms
      Complicated by Aortoenteric or Aortobronchial Fistulae.
AB  - BACKGROUND: The aim of this study was to compare outcomes and identify factors
      related to increased mortality of open surgical and endovascular aortic repair
      (EVAR) of primary mycotic aortic aneurysms complicated by aortoenteric fistula
      (AEF) or aortobronchial fistula (ABF). METHODS: Patients with primary mycotic
      aortic aneurysms complicated by an AEF or ABF treated by open surgery or
      endovascular repair between January 1993 and January 2014 were retrospectively
      reviewed. Outcomes were compared between the open surgery and endovascular
      groups, and a Cox's proportional hazard model was used to determine factors
      associated with mortality. RESULTS: A total of 29 patients included 14 received
      open surgery and 15 received endovascular repair. Positive initial bacterial
      blood culture results included Salmonella spp., oxacillin-resistant
      Staphylococcus aureus, and Klebsiella pneumoniae. Mortality within 1 month of
      surgery was higher in the open surgery than in the endovascular group (43 vs. 7%,
      respectively, p = 0.035). Shock, additional surgery to repair gastrointestinal
      (GI) or airway pathology, and aneurysm rupture were associated with a higher risk
      of death. Compared with patients without resection surgery, the adjusted hazard
      ratio of death within 4 years in patients with resection for GI/bronchial disease
      was 0.25. Survival within 6 months was better in the endovascular group (p =
      0.016). CONCLUSION: The results of this study showed that EVAR/thoracic EVAR
      (TEVAR) is feasible for the management of infected aortic aneurysms complicated
      by an AEF or ABF, and results in good short-term outcomes. However, EVAR/TEVAR
      did not benefit long-term survival compared with open surgery.

PMID- 29207436
TI  - [Dysphagia in a patient with postcricoidal lesion].

PMID- 29207437
TI  - Unfavourable outcome of glucocorticoid treatment in suspected idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: The diagnostic classification of 'possible idiopathic
      pulmonary fibrosis (posIPF)' is characterized by a radiological pattern of
      inconsistent usual interstitial pneumonia (UIP) on high-resolution computed
      tomography (HRCT) scan and a UIP pattern in surgical lung biopsy (SLB). The
      evidence base to guide treatment for patients with posIPF is lacking; the
      clinician must choose between observation, treatment with immunomodulatory agents
      or anti-fibrotic agents. METHODS: To evaluate outcomes of immunomodulatory
      treatment, a multicentre cohort of 59 posIPF patients treated with prednisone was
      analysed retrospectively. Prednisone starting dose was 0.5 mg/kg/day and tapered
      to 0.15 mg/day/kg over 6 months. Outcome measures were forced vital capacity
      (FVC) and serious adverse events (SAE), defined as death or hospital admissions.
      RESULTS: The majority of prednisone-treated posIPF patients were non-responders
      (68%) with a decrease in FVC >5% or death within 6 months from baseline; 90% of
      patients with radiographical presence of honeycombing were non-responders. In
      contrast, six out of seven patients with focal desquamative interstitial
      pneumonia-like reaction in the SLB who had stopped smoking for <5 years ago were
      responders to prednisone, demonstrating <5% FVC decline. The mean decline of FVC
      was 8.7% (95% CI: 3.1-14.3%) before treatment and 20% (95% CI: 9.4-31.1%) after
      treatment (P = 0.018) in the 32 patients with available FVC data. Twelve SAE
      occurred within the first 3 months on prednisone (at dosage >0.3 mg/kg/day),
      including five deaths. CONCLUSION: Patients with posIPF demonstrated an
      accelerated FVC decline and a substantial number of SAE on steroid therapy.

PMID- 29207439
TI  - The world of molecular data is not enough - we still need more algal
      ultrastructure.

PMID- 29207438
TI  - Caterpillars induce jasmonates in flowers and alter plant responses to a second
      attacker.
AB  - In nature, herbivorous insects and plant pathogens are generally abundant when
      plants are flowering. Thus, plants face a diversity of attackers during their
      reproductive phase. Plant responses to one attacker can interfere with responses
      to a second attacker, and phytohormones that orchestrate plant reproduction are
      also involved in resistance to insect and pathogen attack. We quantified
      phytohormonal responses of flowering plants exposed to single or dual attack and
      studied resistance mechanisms of plants in the flowering stage. Flowering
      Brassica nigra were exposed to either a chewing caterpillar, a phloem-feeding
      aphid or a bacterial pathogen, and plant hormonal responses were compared with
      dual attack situations. We quantified phytohormones in inflorescences and leaves,
      and determined the consequences of hormonal changes for components of direct and
      indirect plant resistance. Caterpillars were the main inducers of jasmonates in
      inflorescences, and the phytohormonal profile of leaves was not affected by
      either insect or pathogen attack. Dual attack increased plant resistance to
      caterpillars, but compromised resistance to aphids. Parasitoid performance was
      negatively correlated with the performance of their hosts. We conclude that
      plants prioritize resistance of reproductive tissues over vegetative tissues, and
      that a chewing herbivore species is the main driver of responses in flowering B.
      nigra.

PMID- 29207440
TI  - Understanding the stoichiometric limitation of herbivore growth: the importance
      of feeding and assimilation flexibilities.
AB  - Ecological stoichiometry suggests that herbivore growth is limited by phosphorus
      when this element in the diet is < 8.6 MUg P mg C-1 (C : P atomic ratio > 300).
      However, in nature, it is not necessarily related to the relative phosphorus
      content in diets. This may be the result of complex feeding and assimilation
      responses to diets. We examined these possibilities using herbivorous plankton
      fed mono-specific and mixed algae varying in phosphorus content of 1.6 to 8.1 MUg
      P mg C-1 . The herbivores showed a 10-fold growth rate difference among the
      diets. Growth rates related poorly with phosphorus content in the diets (r2  =
      0.07), better with P ingestion rate (r2  = 0.41) and best with phosphorus
      assimilation rate (r2  = 0.69). Inclusion of assimilation rates for carbon and
      fatty acids increased 7% of the explained growth variance. These results indicate
      that the feeding and assimilation flexibilities play pivotal roles in acquiring a
      deficient element and in regulating growth rate.

PMID- 29207441
TI  - The impact of host genetic diversity on virus evolution and emergence.
AB  - Accumulating evidence indicates that biodiversity has an important impact on
      parasite evolution and emergence. The vast majority of studies in this area have
      only considered the diversity of species within an environment as an overall
      measure of biodiversity, overlooking the role of genetic diversity within a
      particular host species. Although theoretical models propose that host genetic
      diversity in part shapes that of the infecting parasite population, and hence
      modulates the risk of parasite emergence, this effect has seldom been tested
      empirically. Using Rabies virus (RABV) as a model parasite, we provide evidence
      that greater host genetic diversity increases both parasite genetic diversity and
      the likelihood of a host being a donor in RABV cross-species transmission events.
      We conclude that host genetic diversity may be an important determinant of
      parasite evolution and emergence.

PMID- 29207442
TI  - Using the CAUSE Model to Understand Public Communication about Water Risks:
      Perspectives from Texas Groundwater District Officials on Drought and
      Availability.
AB  - Public communication about drought and water availability risks poses challenges
      to a potentially disinterested public. Water management professionals, though,
      have a responsibility to work with the public to engage in communication about
      water and environmental risks. Because limited research in water management
      examines organizational communication practices and perceptions, insights into
      research and practice can be gained through investigation of current applications
      of these risk communication efforts. Guided by the CAUSE model, which explains
      common goals in communicating risk information to the public (e.g., creating
      Confidence, generating Awareness, enhancing Understanding, gaining Satisfaction,
      and motivating Enactment), semistructured interviews of professionals (N = 25)
      employed by Texas groundwater conservation districts were conducted. The
      interviews examined how CAUSE model considerations factor in to communication
      about drought and water availability risks. These data suggest that many work to
      build constituents' confidence in their districts. Although audiences and
      constituents living in drought-prone areas were reported as being engaged with
      water availability risks and solutions, many district officials noted
      constituents' lack of perceived risk and engagement. Some managers also indicated
      that public understanding was a secondary concern of their primary
      responsibilities and that the public often seemed apathetic about technical
      details related to water conservation risks. Overall, results suggest complicated
      dynamics between officials and the public regarding information access and
      motivation. The article also outlines extensions of the CAUSE model and
      implications for improving public communication about drought and water
      availability risks.

PMID- 29207443
TI  - Carcinoid tumour of soft tissue: Primary or metastasis?

PMID- 29207444
TI  - Abnormal B Cell Development in Systemic Lupus Erythematosus: What the Genetics
      Tell Us.

PMID- 29207445
TI  - Risk Reduction of Breast Cancer by Childbirth, Breastfeeding, and Their
      Interaction in Korean Women: Heterogeneous Effects Across Menopausal Status,
      Hormone Receptor Status, and Pathological Subtypes.
AB  - Objectives: The purpose of this study was to examine the associations of
      childbirth, breastfeeding, and their interaction with breast cancer (BC) risk
      reduction, and to evaluate the heterogeneity in the BC risk reduction effects of
      these factors by menopause, hormone receptor (HR) status, and pathological
      subtype. Methods: BC patients aged 40+ from the Korean Breast Cancer Registry in
      2004-2012 and controls from the Health Examinee cohort participants were included
      in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC
      risk according to childbirth, breast-feeding, and their interaction was
      calculated in logistic regression models using odds ratios (ORs) and 95%
      confidence intervals (CIs). Results: BC risk decreased with childbirth (3+
      childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR,
      0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women,
      respectively); and the degree of risk reduction by the number of children was
      heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p
      heterogeneity<0.001), and pathological subtype (p-heterogeneity<0.001); whereas
      breastfeeding for 1-12 months showed a heterogeneous association with BC risk
      according to menopausal status, with risk reduction only in premenopausal women
      (p-heterogeneity<0.05). The combination of 2 more childbirths and breastfeeding
      for >=13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI,
      0.45 to 0.58). Conclusions: This study suggests that the combination of longer
      breastfeeding and more childbirths reduces BC risk more strongly, and that women
      who experience both 2 or more childbirths and breastfeed for >=13 months can
      reduce their BC risk by about 50%.

PMID- 29207446
TI  - Has the Copayment Ceiling Improved Financial Protection in the Korean National
      Health Insurance System? Evidence From the 2009 Policy Change.
AB  - Objectives: To relieve the financial burden faced by households, the Korean
      National Health Insurance (NHI) system introduced a "copayment ceiling," which
      evolved into a differential ceiling in 2009, with the copayment ceiling depending
      on patients' income. This study aimed to examine the effect of the differential
      copayment ceiling on financial protection and healthcare utilization,
      particularly focusing on whether its effects varied across different income
      groups. Methods: This study obtained data from the Korea Health Panel. The number
      of households included in the analysis was 6555 in 2008, 5859 in 2009, 5539 in
      2010, and 5372 in 2011. To assess the effects of the differential copayment
      ceiling on utilization, out-of-pocket (OOP) payments, and catastrophic payments,
      various random-effects models were applied. Utilization was measured as treatment
      days, while catastrophic payments were defined as OOP payments exceeding 10% of
      household income. Among the right-hand side variables were the interaction terms
      of the new policy with income levels, as well as a set of household
      characteristics. Results: The differential copayment ceiling contributed to
      increased utilization regardless of income levels both in all patients and in
      cancer patients. However, the new policy did not seem to reduce significantly the
      incidence of catastrophic payments among cancer patients, and even increased the
      incidence among all patients. Conclusions: The limited effect of the differential
      ceiling can be attributed to a high proportion of direct payments for services
      not covered by the NHI, as well as the relatively small number of households
      benefiting from the differential ceilings; these considerations warrant a better
      policy design.

PMID- 29207447
TI  - Mercury Exposure in Association With Decrease of Liver Function in Adults: A
      Longitudinal Study.
AB  - Objectives: Although mercury (Hg) exposure is known to be neurotoxic in humans,
      its effects on liver function have been less often reported. The aim of this
      study was to investigate whether total Hg exposure in Korean adults was
      associated with elevated serum levels of the liver enzymes aspartate
      aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase
      (GGT). Methods: We repeatedly examined the levels of total Hg and liver enzymes
      in the blood of 508 adults during 2010-2011 and 2014-2015. Cross-sectional
      associations between levels of blood Hg and liver enzymes were analyzed using a
      generalized linear model, and nonlinear relationships were analyzed using a
      generalized additive mixed model. Generalized estimating equations were applied
      to examine longitudinal associations, considering the correlations of individuals
      measured repeatedly. Results: GGT increased by 11.0% (95% confidence interval
      [CI], 4.5 to 18.0%) in women and 8.1% (95% CI, -0.5 to 17.4%) in men per doubling
      of Hg levels, but AST and ALT were not significantly associated with Hg in either
      men or women. In women who drank more than 2 or 3 times per week, AST, ALT, and
      GGT levels increased by 10.6% (95% CI, 4.2 to 17.5%), 7.7% (95% CI, 1.1 to
      14.7%), and 37.5% (95% CI,15.2 to 64.3%) per doubling of Hg levels, respectively,
      showing an interaction between blood Hg levels and drinking. Conclusions: Hg
      exposure was associated with an elevated serum concentration of GGT. Especially
      in women who were frequent drinkers, AST, ALT, and GGT showed a significant
      increase, with a significant synergistic effect of Hg and alcohol consumption.

PMID- 29207448
TI  - Are Serum Vitamin D Levels Associated With Dry Eye Disease? Results From the
      Study Group for Environmental Eye Disease.
AB  - Objectives: Dry eye disease (DED) is an increasingly important public health
      problem in Korea. Previous studies conducted in Korea have reported inconsistent
      results regarding the protective effects of vitamin D on DED, and these
      discrepancies may be related to the relatively simple questionnaire that has been
      used. Thus, we evaluated the association of serum vitamin D levels with DED using
      the ocular surface disease index (OSDI). Methods: The present study evaluated
      data from participants in the Study Group for Environmental Eye Disease (2014
      2015). This group included data from 752 participants, and data from 740
      participants (253 men and 487 women) were analyzed in the present study. DED
      severity was evaluated using the OSDI. Results: Higher serum vitamin D levels
      were associated with a non-significantly reduced risk of DED in the crude
      analysis (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.971 to 1.011)
      and in the adjusted analysis (OR, 0.988; 95% CI, 0.966 to 1.010). In the crude
      analysis of no/mild DED vs. moderate/severe DED, men exhibited a decreased risk
      with increasing serum vitamin D levels (OR, 0.999; 95% CI, 0.950 to 1.051), while
      women exhibited an increased risk (OR, 1.003; 95% CI, 0.979 to 1.027). In these
      analyses, we found no significant associations. Conclusions: The findings of the
      present study support previous reports that serum vitamin D levels are not
      associated with DED.

PMID- 29207449
TI  - Exploratory Study of Dimensions of Health-related Quality of Life in the General
      Population of South Korea.
AB  - Objectives: This study aimed to explore dimensions in addition to the 5
      dimensions of the 5-level EQ-5D version (EQ-5D-5L) that could satisfactorily
      explain variation in health-related quality of life (HRQoL) in the general
      population of South Korea. Methods: Domains related to HRQoL were searched
      through a review of existing HRQoL instruments. Among the 28 potential
      dimensions, the 5 dimensions of the EQ-5D-5L and 7 additional dimensions (vision,
      hearing, communication, cognitive function, social relationships, vitality, and
      sleep) were included. A representative sample of 600 subjects was selected for
      the survey, which was administered through face-to-face interviews. Subjects were
      asked to report problems in 12 health dimensions at 5 levels, as well as their
      self-rated health status using the EuroQol visual analogue scale (EQ-VAS) and a 5
      point Likert scale. Among subjects who reported no problems for any of the
      parameters in the EQ-5D-5L, we analyzed the frequencies of problems in the
      additional dimensions. A linear regression model with the EQ-VAS as the dependent
      variable was performed to identify additional significant dimensions. Results:
      Among respondents who reported full health on the EQ-5D-5L (n=365), 32% reported
      a problem for at least 1 additional dimension, and 14% reported worse than
      moderate self-rated health. Regression analysis revealed a R2 of 0.228 for the
      original EQ-5D-5L dimensions, 0.200 for the new dimensions, and 0.263 for the 12
      dimensions together. Among the added dimensions, vitality and sleep were
      significantly associated with EQ-VAS scores. Conclusions: This study identified
      significant dimensions for assessing self-rated health among members of the
      general public, in addition to the 5 dimensions of the EQ-5D-5L. These dimensions
      could be considered for inclusion in a new preference-based instrument or for
      developing a country-specific HRQoL instrument.

PMID- 29207450
TI  - One Health Perspectives on Emerging Public Health Threats.
AB  - Antimicrobial resistance and emerging infectious diseases, including avian
      influenza, Ebola virus disease, and Zika virus disease have significantly
      affected humankind in recent years. In the premodern era, no distinction was made
      between animal and human medicine. However, as medical science developed, the gap
      between human and animal science grew deeper. Cooperation among human, animal,
      and environmental sciences to combat emerging public health threats has become an
      important issue under the One Health Initiative. Herein, we presented the history
      of One Health, reviewed current public health threats, and suggested
      opportunities for the field of public health through better understanding of the
      One Health paradigm.

PMID- 29207451
TI  - Cardiovascular Disease-related Health Beliefs and Lifestyle Issues Among Karen
      Refugees Resettled in the United States From the Thai-Myanmar (Burma) Border.
AB  - Objectives: Refugees resettled in the US may be at risk for cardiovascular
      disease (CVD). However, little is known about CVD-related issues among Karen
      refugees who have migrated to the US from the Thai-Myanmar border. The purpose of
      this study was to examine CVD-related health beliefs and lifestyle issues among
      Karen refugees resettled in the US. Methods: Karen refugees resettled in the US
      from the Thai-Myanmar border (n=195) participated in a survey study on health
      beliefs related to CVD, salt intake, physical activity (PA), and smoking in the
      fall of 2016. Results: A high-salt diet, physical inactivity, and smoking were
      major lifestyle problems. Participants who adhered to a low-salt diet considered
      themselves to be susceptible to CVD. Most participants did not engage in regular
      PA. Regular PA was associated with less perceived susceptibility to CVD and
      greater perceived benefits of a healthy lifestyle for decreasing the likelihood
      of CVD. Conclusions: Each refugee population may require individualized
      strategies to promote PA and a healthy diet. Future studies should develop health
      education programs that are specifically designed for Karen refugees and evaluate
      such programs. In addition to health education programs on healthy lifestyle
      choices, tobacco cessation programs seem to be necessary for Karen refugees. At
      the same time, it is important to foster strategies to increase the utilization
      of preventive care among this population by promoting free or reduced-fee
      resources in the community to further promote their health.

PMID- 29207452
TI  - Congenital Malformations in Infants of Mothers Undergoing Assisted Reproductive
      Technologies: A Systematic Review and Meta-analysis Study.
AB  - Objectives: This meta-analysis aimed to evaluate congenital malformations in
      infants conceived by assisted reproductive techniques (ART), compared with
      infants conceived spontaneously. Methods: In this study, available resources
      searched to find relevant articles included PubMed, ScienceDirect, Scopus, Google
      Scholar, Cochrane, ProQuest, Iranmedex, Magiran, and Scientific Information
      Database. After extracting the necessary information from evaluated articles,
      meta-analysis on the articles' data was performed using Stata version 11.2.
      Results: In this study, from a total of 339 articles, extracted from the initial
      investigation, ultimately 30 articles were selected for meta-analysis that
      assessed the use of ART on the risk of congenital abnormalities and some birth
      complications on 5 470 181 infants (315 402 cases and 5 154 779 controls). The
      odds ratio (95% confidence interval [CI]) for low birth weight was 1.89 (95% CI,
      1.36 to 2.62), preterm labor 1.79 (95% CI, 1.21 to 2.63), cardiac abnormalities
      1.43 (95% CI, 1.27 to 1.62), central nervous system abnormalities 1.36 (95% CI,
      1.10 to 1.70), urogenital system abnormalities 1.58 (95% CI, 1.28 to 1.94),
      musculoskeletal disorders 1.35 (95% CI, 1.12 to 1.64), and chromosomal
      abnormalities in infants conceived by ART was 1.14 (95% CI, 0.90 to 1.44), which
      were all statistically significant, except chromosomal abnormalities.
      Conclusions: The risk of congenital abnormalities and some birth complications
      were significantly higher in ART than normal conception, while chromosomal
      abnormalities were not; therefore, the application of ART should be selected
      individually for patients by detailed assessment to reduce such risks in the
      population.

PMID- 29207453
TI  - How to successfully list a journal in the Social Science Citation Index or
      Science Citation Index Expanded.

PMID- 29207454
TI  - Podcasting in medical education: a review of the literature.
AB  - Podcasts are increasingly being used for medical education, both within teaching
      institutions and on an international scale by major journals. To date, there are
      no evidence-based guidelines for the development of educational podcasts. To
      review the state of the literature, MEDLINE, SCOPUS, and ERIC were searched in
      May 2016 for articles describing audio format podcasts used in medical education.
      Eighty-four articles met inclusion criteria. A qualitative synthesis of the
      evidence was done using Kirkpatrick's model for evaluating outcomes. Twenty-four
      articles described reaction outcomes, eleven described learning outcomes, and one
      described behavioral outcomes. None measured patient impact. The literature
      demonstrates that podcasts are both feasible and accepted by learners. The mean
      length of reported podcasts was 18 minutes, which falls within the recommended
      range in at least one paper, and is consistent with reported listener preference.
      Interview format, clear disclosures, and accurate information were reported as
      desirable. There is limited evidence showing the efficacy of podcasts as teaching
      tools, or regarding best practices in making podcasts. More rigorous studies
      evaluating efficacy, changes in behavior, and changes in patient outcomes need to
      be performed in order to prove podcasts' value and to justify production costs.

PMID- 29207455
TI  - Verbal communication of students with high patient-physician interaction scores
      in a clinical performance examination assessed by standardized patients.
AB  - PURPOSE: Standardized patients (SPs) tend to rate medical students' communication
      skills subjectively and comprehensively, in contrast to such objective skill set
      defined in the clinical performance examination (CPX). Meanwhile, medical school
      instructors have a different approach in their evaluation of students'
      communication skills. We aim to analyze medical students' verbal communication
      skills using objective methods, and to determine the contributing factors of a
      patient-physician interaction (PPI) score. METHODS: Students with high- and low
      ranking scores for PPI in CPX were selected. The Roter interaction analysis
      system was used to compare verbal communication behaviors of the students and
      SPs. Patient-centeredness scores (PCSs), physician's verbal dominance, and number
      of utterances were compared between the two groups. RESULTS: PCSs and physician's
      verbal dominance had no difference between the groups. The number of utterances
      during the limited time of 5 minutes of CPX was higher for the high-ranking
      students. They tended to employ more paraphrase/check for understanding, and
      closed questions for psychosocial state and open questions for medical condition.
      The SPs interviewed by high-ranking students gave more medical information and
      requested for more services. CONCLUSION: In the case of the routine checkup,
      smooth conversations with more frequent utterances were detected in the high
      ranking students. More medical information exchange and requests for services by
      SPs were higher for the high-ranking students. Medical communication instructors
      should keep in mind that our results could be indicators of a high PPI score.

PMID- 29207456
TI  - A study of satisfaction of medical students on their mentoring programs at one
      medical school in Korea.
AB  - PURPOSE: The purpose of this study was to investigate the awareness levels of
      medical students regarding the characteristics of each function within a
      mentoring program conducted within Kyung Hee University and to ultimately suggest
      points for reformation. Medical students' awareness levels were determined using
      a 29-item questionnaire. METHODS: The questionnaire was conducted on 347 medical
      students, excluding 25 students who either marked multiple answers or did not
      reply. The assessment of the program was based on a questionnaire with the use of
      a 5-point Likert scale using SPSS version 22.0. Multiple regression was conducted
      to examine the relationship between the satisfaction level, regarding functions
      of mentoring programs, and characteristics of mentoring programs. Interviews were
      conducted to supplement additional information that was hard to gain from the
      questionnaire. RESULTS: The results on demographic and functional characteristics
      revealed that there was no statistically significant differences in satisfaction
      levels across gender, whereas there were significant differences across grade
      levels. In addition, there were significant differences in the frequency of
      meetings and topics of conversation while the length of meetings and meeting
      place were not significantly different. CONCLUSION: For the improved mentoring
      programs for medical students, the program should focus on the frequency of
      meetings and the topics of conversation. Furthermore, mentoring programs of high
      quality can be expected if professors take interview results into consideration.
      Also, students want to be provided with psychosocial advice from mentors in
      various ways such as role model function.

PMID- 29207457
TI  - Verification of learner's differences by team-based learning in biochemistry
      classes.
AB  - PURPOSE: We tested the effect of team-based learning (TBL) on medical education
      through the second-year premedical students' TBL scores in biochemistry classes
      over 5 years. METHODS: We analyzed the results based on test scores before and
      after the students' debate. The groups of students for statistical analysis were
      divided as follows: group 1 comprised the top-ranked students, group 3 comprised
      the low-ranked students, and group 2 comprised the medium-ranked students.
      Therefore, group T comprised 382 students (the total number of students in group
      1, 2, and 3). To calibrate the difficulty of the test, original scores were
      converted into standardized scores. We determined the differences of the tests
      using Student t-test, and the relationship between scores before, and after the
      TBL using linear regression tests. RESULTS: Although there was a decrease in the
      lowest score, group T and 3 showed a significant increase in both original and
      standardized scores; there was also an increase in the standardized score of
      group 3. There was a positive correlation between the pre- and the post-debate
      scores in group T, and 2. And the beta values of the pre-debate scores and "the
      changes between the pre- and post-debate scores" were statistically significant
      in both original and standardized scores. CONCLUSION: TBL is one of the
      educational methods for helping students improve their grades, particularly those
      of low-ranked students.

PMID- 29207458
TI  - Implementation of problem-based learning in medical education in Korea.
AB  - PURPOSE: This study aims to identify how problem-based learning (PBL) has been
      implemented in Korean medical education, and how it is evaluated by each medical
      school. METHODS: For this study, a total of 40 medical schools in Korea were
      surveyed via e-mail. The survey tool was a questionnaire consisting of 22
      questions which was developed independently by the researchers. RESULTS: Of the
      40 medical schools, 35 schools were implementing PBL programs in their medical
      curriculum, while five were found not currently to be running the program. A
      large number of the schools which introduced PBL (30 schools, 85.7%) used a
      hybrid PBL model. In over 70% of the medical schools surveyed, professors
      evaluated the effects of PBL as positive. Most medical schools (85.7%) stated
      they would maintain or expand their use of PBL. However, the lack of
      understanding and skeptical attitude of the faculty on PBL, the lack of self
      study time and passive attitude of students, insufficiency of good PBL cases, and
      the perfunctory PBL introduction for school accreditation interfere with the
      successful PBL. CONCLUSION: PBL has been incorporated in Korean medical
      curriculum as hybrid PBL type. It is analyzed that intensive tutor training and
      good PBL case development are necessary for the success and effective operation
      of PBL.

PMID- 29207459
TI  - The challenges of medical education in developing "true medical professionalism".

PMID- 29207460
TI  - An epilogue to an emergency-trauma practicum.

PMID- 29207461
TI  - Effect of Solution Treatment on Precipitation Behaviors, Age Hardening Response
      and Creep Properties of Elektron21 Alloy Reinforced by AlN Nanoparticles.
AB  - In the present study, the solution and ageing treatments behavior of Mg-RE-Zr-Zn
      alloy (Elektron21) and its nano-AlN reinforced nanocomposites have been
      evaluated. The properties of the thermal-treated materials were investigated in
      terms of Vickers hardness, the area fraction of precipitates, microstructure and
      phase composition. The solution treatments were performed by treating at 520 
      degrees C, 550  degrees C and 580  degrees C in argon atmosphere. The outcomes
      show that the hardness of the solutionized alloys was slightly affected by the
      solution temperature. X-ray diffraction and image analysis revealed that the
      complete dissolution of precipitates was not possible, neither for Elektron21
      (El21) nor for its AlN containing nanocomposites. The ageing treatment of El21
      led to a significant improvement in hardness after 20 h, while for longer times,
      it progressively decreased. The effect of ageing on the hardness of El21-AlN
      composites was found to be much less than this effect on the hardness of the host
      alloy. Electron backscatter diffraction (EBSD) analysis of El21 and El21-1%AlN
      after solution treatment confirm the random orientation of grains with a typical
      texture of random distribution. The as-cast creep results showed that the
      incorporation of nanoparticles could effectively improve the creep properties,
      while the results after solution treatment at 520  degrees C for 12 h followed by
      ageing treatment at 200  degrees C for 20 h confirmed that the minimum creep rate
      of T6-El21 was almost equal to the as-cast El21-AlN.

PMID- 29207462
TI  - Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and
      New Prospective.
AB  - In 2017, the 200th anniversary of the discovery of selenium was celebrated. In
      1817, the Swedish chemists, Berzelius and Gahn, on roasting 200 kg of sulfur from
      a pyrite from the Falun mine, obtained about 3 g of a precipitate that they first
      wrongly identified as tellurium. Berzelius doubted this result and repeated the
      analysis some months later realizing that a new element was in his hands and he
      named this element Selenium (Greek: Selene, moon) in consideration of its
      resemblance to Tellurium (Latin: Tellus, earth). Several events were organized in
      the year for this special celebration and this Special Issue would like to be an
      additional contribution to the success of a research that, especially during the
      last decades, rapidly grew in different fields: synthesis, medicinal chemistry,
      biology, material, and environment. These studies are strongly characterized by
      multi- and interdisciplinary connections, and, for this reason, we collected here
      contributions coming from different areas and disciplines, not exclusively
      synthetic organic chemistry.

PMID- 29207463
TI  - Synthesis and Characterization of Polyaniline/Graphene Composite Nanofiber and
      Its Application as an Electrochemical DNA Biosensor for the Detection of
      Mycobacterium tuberculosis.
AB  - This article describes chemically modified polyaniline and graphene (PANI/GP)
      composite nanofibers prepared by self-assembly process using oxidative
      polymerization of aniline monomer and graphene in the presence of a solution
      containing poly(methyl vinyl ether-alt-maleic acid) (PMVEA). Characterization of
      the composite nanofibers was carried out by Fourier transform infrared (FTIR) and
      Raman spectroscopy, transmission electron microscopy (TEM) and scanning electron
      microscopy (SEM). SEM images revealed the size of the PANI nanofibers ranged from
      90 to 360 nm in diameter and was greatly influenced by the proportion of PMVEA
      and graphene. The composite nanofibers with an immobilized DNA probe were used
      for the detection of Mycobacterium tuberculosis by using an electrochemical
      technique. A photochemical indicator, methylene blue (MB) was used to monitor the
      hybridization of target DNA by using differential pulse voltammetry (DPV) method.
      The detection range of DNA biosensor was obtained from of 10-6-10-9 M with the
      detection limit of 7.853 * 10-7 M under optimum conditions. The results show that
      the composite nanofibers have a great potential in a range of applications for
      DNA sensors.

PMID- 29207464
TI  - Synthesis, Characterization and Antibacterial Activity of Novel 1,3-Diethyl-1,3
      bis(4-nitrophenyl)urea and Its Metal(II) Complexes.
AB  - A bioactive ligand and its dinuclear metal(II) complexes were synthesized and
      characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet
      visible (UV-Visible), nuclear magnetic resonance (1H-NMR), mass spectroscopy and
      molar conductance measurements. The ligand has been crystalized in the monoclinic
      system with a P21/c space group. The biological activities of metal complexes
      were evaluated using disc diffusion and broth dilution methods. In vitro
      antibacterial activities of the ligand and their metal complexes were examined
      against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus)
      and two Gram-negative bacteria (Escherichia coli and Serratia marcescens) and
      compared to the standard drugs. It was found that metal complexes displayed much
      higher antibacterial activities and better inhibitory effects than that of the
      ligand and standard drugs. Among these complexes, the compound having Zn-metal
      showed greater antibacterial activity against all four tested bacteria and was
      more effective against Serratia marcescens with the zone inhibition diameter of
      26 mm and MIC value of 31.25 ug/mL.

PMID- 29207465
TI  - gammaPNA FRET Pair Miniprobes for Quantitative Fluorescent In Situ Hybridization
      to Telomeric DNA in Cells and Tissue.
AB  - Measurement of telomere length by fluorescent in situ hybridization is widely
      used for biomedical and epidemiological research, but there has been relatively
      little development of the technology in the 20 years since it was first reported.
      This report describes the use of dual gammaPNA (gammaPNA) probes that hybridize
      at alternating sites along a telomere and give rise to Forster resonance energy
      transfer (FRET) signals. Bright staining of telomeres is observed in nuclei,
      chromosome spreads and tissue samples. The use of FRET detection also allows for
      elimination of wash steps, normally required to remove unhybridized probes that
      would contribute to background signals. We found that these wash steps can
      diminish the signal intensity through the removal of bound, as well as unbound
      probes, so eliminating these steps not only accelerates the process but also
      enhances the quality of staining. Thus, gammaPNA FRET pairs allow for brighter
      and faster staining of telomeres in a wide range of research and clinical
      formats.

PMID- 29207466
TI  - Evaluation of Poly(Lactic-co-glycolic) Acid Alone or in Combination with
      Hydroxyapatite on Human-Periosteal Cells Bone Differentiation and in Sinus Lift
      Treatment.
AB  - Most recent advances in tissue engineering in the fields of oral surgery and
      dentistry have aimed to restore hard and soft tissues. Further improvement of
      these therapies may involve more biological approaches and the use of dental
      tissue stem cells in combination with inorganic/organic scaffolds. In this study,
      we analyzed the osteoconductivity of two different inorganic scaffolds based on
      poly (lactic-co-glycolic) acid alone (PLGA-Fisiograft) or in combination with
      hydroxyapatite (PLGA/HA-Alos) in comparison with an organic material based on
      equine collagen (PARASORB Sombrero) both in vitro and in vivo. We developed a
      simple in vitro model in which periosteum-derived stem cells were grown in
      contact with chips of these scaffolds to mimic bone mineralization. The viability
      of cells and material osteoconductivity were evaluated by osteogenic gene
      expression and histological analyses at different time points. In addition, the
      capacity of scaffolds to improve bone healing in sinus lift was examined. Our
      results demonstrated that the osteoconductivity of PLGA/HA-Alos and the efficacy
      of scaffolds in promoting bone healing in the sinus lift were increased. Thus,
      new clinical approaches in sinus lift follow-up should be considered to elucidate
      the clinical potential of these two PLGA-based materials in dentistry.

PMID- 29207467
TI  - Review of Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of
      Euclea natalensis A.DC.
AB  - Euclea natalensis is traditionally used as herbal medicine for several human
      diseases and ailments in tropical Africa. This study reviews information on
      ethnomedicinal uses, botany, phytochemical constituents, pharmacology and
      toxicity of E. natalensis. Results of this study are based on literature search
      from several sources including electronic databases, books, book chapters,
      websites, theses and conference proceedings. This study showed that E. natalensis
      is used as traditional medicine in 57.1% of the countries where it is indigenous.
      Euclea natalensis has a high degree of consensus on abdominal pains, antidote for
      snake bites, diabetes, diarrhoea, malaria, roundworms, stomach problems,
      toothache, venereal diseases and wounds. Several ethnopharmacological studies
      have shown that crude extracts and chemical compounds from E. natalensis
      demonstrated many biological activities both in vitro and in vivo, which included
      antibacterial, antidiabetic, antifungal, antimycobacterial, antiviral,
      antioxidant, antiplasmodial, larvicidal, antischistosomal, molluscicidal, dentin
      permeability and hepatoprotective activities. Future studies should focus on the
      mechanism of biological activities of both crude extracts and chemical compounds
      from the species, as well as structure-function relationships of bioactive
      constituents of the species.

PMID- 29207468
TI  - Vertical Optical Scanning with Panoramic Vision for Tree Trunk Reconstruction.
AB  - This paper presents a practical application of a technique that uses a vertical
      optical flow with a fisheye camera to generate dense point clouds from a single
      planimetric station. Accurate data can be extracted to enable the measurement of
      tree trunks or branches. The images that are collected with this technique can be
      oriented in photogrammetric software (using fisheye models) and used to generate
      dense point clouds, provided that some constraints on the camera positions are
      adopted. A set of images was captured in a forest plot in the experiments.
      Weighted geometric constraints were imposed in the photogrammetric software to
      calculate the image orientation, perform dense image matching, and accurately
      generate a 3D point cloud. The tree trunks in the scenes were reconstructed and
      mapped in a local reference system. The accuracy assessment was based on
      differences between measured and estimated trunk diameters at different heights.
      Trunk sections from an image-based point cloud were also compared to the
      corresponding sections that were extracted from a dense terrestrial laser
      scanning (TLS) point cloud. Cylindrical fitting of the trunk sections allowed the
      assessment of the accuracies of the trunk geometric shapes in both clouds. The
      average difference between the cylinders that were fitted to the photogrammetric
      cloud and those to the TLS cloud was less than 1 cm, which indicates the
      potential of the proposed technique. The point densities that were obtained with
      vertical optical scanning were 1/3 less than those that were obtained with TLS.
      However, the point density can be improved by using higher resolution cameras.

PMID- 29207469
TI  - Eating at Food Outlets and "On the Go" Is Associated with Less Healthy Food
      Choices in Adults: Cross-Sectional Data from the UK National Diet and Nutrition
      Survey Rolling Programme (2008-2014).
AB  - Eating location has been linked with variations in diet quality including the
      consumption of low-nutrient energy-dense food, which is a recognised risk factor
      for obesity. Cross-sectional data from 4736 adults aged 19 years and over from
      Years 1-6 of the UK National Diet and Nutrition Survey (NDNS) Rolling Programme
      (RP) (2008-2014) were used to explore food consumption patterns by eating
      location. Eating location was categorized as home, work, leisure places, food
      outlets and "on the go". Foods were classified into two groups: core (included in
      the principal food groups and considered important/acceptable within a healthy
      diet) and non-core (all other foods). Out of 97,748 eating occasions reported,
      the most common was home (67-90% of eating occasions). Leisure places, food
      outlets and "on the go" combined contributed more energy from non-core (30%) than
      from core food (18%). Analyses of modulating factors revealed that sex, income,
      frequency of eating out and frequency of drinking were significant factors
      affecting consumption patterns (p < 0.01). Our study provides evidence that
      eating patterns, behaviours and resulting diet quality vary by location. Public
      health interventions should focus on availability and access to healthy foods,
      promotion of healthy food choices and behaviours across multiple locations,
      environments and contexts for food consumption.

PMID- 29207470
TI  - Repetitively Mode-Locked Cavity-Enhanced Absorption Spectroscopy (RML-CEAS) for
      Near-Infrared Gas Sensing.
AB  - A Pound-Drever-Hall (PDH)-based mode-locked cavity-enhanced sensor system was
      developed using a distributed feedback diode laser centered at 1.53 um as the
      laser source. Laser temperature scanning, bias control of the piezoelectric
      ceramic transducer (PZT) and proportional-integral-derivative (PID) feedback
      control of diode laser current were used to repetitively lock the laser modes to
      the cavity modes. A gas absorption spectrum was obtained by using a series of
      absorption data from the discrete mode-locked points. The 15 cm-long Fabry-Perot
      cavity was sealed using an enclosure with an inlet and outlet for gas pumping and
      a PZT for cavity length tuning. The performance of the sensor system was
      evaluated by conducting water vapor measurements. A linear relationship was
      observed between the measured absorption signal amplitude and the H2O
      concentration. A minimum detectable absorption coefficient of 1.5 * 10-8 cm-1 was
      achieved with an averaging time of 700 s. This technique can also be used for the
      detection of other trace gas species by targeting the corresponding gas
      absorption line.

PMID- 29207471
TI  - Nuts and Human Health Outcomes: A Systematic Review.
AB  - There has been increasing interest in nuts and their outcome regarding human
      health. The consumption of nuts is frequently associated with reduction in risk
      factors for chronic diseases. Although nuts are high calorie foods, several
      studies have reported beneficial effects after nut consumption, due to fatty acid
      profiles, vegetable proteins, fibers, vitamins, minerals, carotenoids, and
      phytosterols with potential antioxidant action. However, the current findings
      about the benefits of nut consumption on human health have not yet been clearly
      discussed. This review highlights the effects of nut consumption on the context
      of human health.

PMID- 29207472
TI  - Effects of beta-Hydroxy-beta-methylbutyrate-free Acid Supplementation on
      Strength, Power and Hormonal Adaptations Following Resistance Training.
AB  - BACKGROUND: beta-Hydroxy-beta-methylbutyrate-free acid (HMB-FA) has been ingested
      prior to exercise to reduce muscle damage, however the effects of HMB-FA
      supplementation on hormonal, strength and power adaptation are unclear. METHODS:
      Sixteen healthy men were matched and randomized into two groups and performed six
      week resistance training while supplementing with either HMB-FA or placebo (3 g
      per day). The subjects were evaluated for 1 repetition maximum (1RM) bench press
      and leg press and vertical jump (VJ) prior to and after training intervention. In
      addition, blood samples were obtained before and after resistance training to
      evaluate resting growth hormone (GH), insulin like growth factor 1 (IGF-1),
      testosterone (TEST), cortisol (CORT), and adrenocorticotropic hormone (ACTH)
      responses. The HMB-FA supplementation group showed greater gains compared with
      the placebo group in peak power (effect size ES = 0.26 vs. 0.01) and 1RM leg
      press (ES = 1.52 vs. 0.96). In addition, the HMB-FA supplementation group
      indicated greater decrements in ACTH and CORT responses to training in comparison
      to the placebo group (p < 0.05). Likewise, in GH (ES = 1.41 vs. 0.12) and IGF-1
      (ES = 0.83 vs. 0.41), the HMB-FA indicated greater training effects when compared
      with the placebo group. CONCLUSIONS: These findings provide further support for
      the potential anabolic benefits associated with HMB-FA supplementation.

PMID- 29207473
TI  - The Cost-Effectiveness of Lowering Permissible Noise Levels Around U.S. Airports.
AB  - Aircraft noise increases the risk of cardiovascular diseases and mental illness.
      The allowable limit for sound in the vicinity of an airport is 65 decibels (dB)
      averaged over a 24-h 'day and night' period (DNL) in the United States. We
      evaluate the trade-off between the cost and the health benefits of changing the
      regulatory DNL level from 65 dB to 55 dB using a Markov model. The study used
      LaGuardia Airport (LGA) as a case study. In compliance with 55 dB allowable limit
      of aircraft noise, sound insulation would be required for residential homes
      within the 55 dB to 65 dB DNL. A Markov model was built to assess the cost
      effectiveness of installing sound insulation. One-way sensitivity analyses and
      Monte Carlo simulation were conducted to test uncertainty of the model. The
      incremental cost-effectiveness ratio of installing sound insulation for residents
      exposed to airplane noise from LGA was $11,163/QALY gained (95% credible
      interval: cost-saving and life-saving to $93,054/QALY gained). Changing the
      regulatory standard for noise exposure around airports from 65 dB to 55 dB comes
      at a very good value.

PMID- 29207474
TI  - Emerging Roles of Mitochondrial Ribosomal Proteins in Plant Development.
AB  - Mitochondria are the powerhouse of eukaryotic cells because they are responsible
      for energy production through the aerobic respiration required for growth and
      development. These organelles harbour their own genomes and translational
      apparatus: mitochondrial ribosomes or mitoribosomes. Deficient mitochondrial
      translation would impair the activity of this organelle, and is expected to
      severely perturb different biological processes of eukaryotic organisms. In
      plants, mitoribosomes consist of three rRNA molecules, encoded by the
      mitochondrial genome, and an undefined set of ribosomal proteins (mitoRPs),
      encoded by nuclear and organelle genomes. A detailed functional and structural
      characterisation of the mitochondrial translation apparatus in plants is
      currently lacking. In some plant species, presence of small gene families of
      mitoRPs whose members have functionally diverged has led to the proposal of the
      heterogeneity of the mitoribosomes. This hypothesis supports a dynamic
      composition of the mitoribosomes. Information on the effects of the impaired
      function of mitoRPs on plant development is extremely scarce. Nonetheless,
      several works have recently reported the phenotypic and molecular
      characterisation of plant mutants affected in mitoRPs that exhibit alterations in
      specific development aspects, such as embryogenesis, leaf morphogenesis or the
      formation of reproductive tissues. Some of these results would be in line with
      the ribosomal filter hypothesis, which proposes that ribosomes, besides being the
      machinery responsible for performing translation, are also able to regulate gene
      expression. This review describes the phenotypic effects on plant development
      displayed by the mutants characterised to date that are defective in genes which
      encode mitoRPs. The elucidation of plant mitoRPs functions will provide a better
      understanding of the mechanisms that control organelle gene expression and their
      contribution to plant growth and morphogenesis.

PMID- 29207475
TI  - Function of microRNAs in the Osteogenic Differentiation and Therapeutic
      Application of Adipose-Derived Stem Cells (ASCs).
AB  - Traumatic wounds with segmental bone defects represent substantial reconstructive
      challenges. Autologous bone grafting is considered the gold standard for surgical
      treatment in many cases, but donor site morbidity and associated post-operative
      complications remain a concern. Advances in regenerative techniques utilizing
      mesenchymal stem cell populations from bone and adipose tissue have opened the
      door to improving bone repair in the limbs, spine, and craniofacial skeleton. The
      widespread availability, ease of extraction, and lack of immunogenicity have made
      adipose-derived stem cells (ASCs) particularly attractive as a stem cell source
      for regenerative strategies. Recently it has been shown that small, non-coding
      miRNAs are involved in the osteogenic differentiation of ASCs. Specifically,
      microRNAs such as miR-17, miR-23a, and miR-31 are expressed during the osteogenic
      differentiation of ASCs, and appear to play a role in inhibiting various steps in
      bone morphogenetic protein-2 (BMP2) mediated osteogenesis. Importantly, a number
      of microRNAs including miR-17 and miR-31 that act to attenuate the osteogenic
      differentiation of ASCs are themselves stimulated by transforming growth factor
      beta-1 (TGFbeta-1). In addition, transforming growth factor beta-1 is also known
      to suppress the expression of microRNAs involved in myogenic differentiation.
      These data suggest that preconditioning strategies to reduce TGFbeta-1 activity
      in ASCs may improve the therapeutic potential of ASCs for musculoskeletal
      application. Moreover, these findings support the isolation of ASCs from
      subcutaneous fat depots that tend to have low endogenous levels of TGFbeta-1
      expression.

PMID- 29207476
TI  - Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced
      Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy.
AB  - The aim of this study was to investigate the protective effects and mechanisms of
      hesperidin, a plant based active flavanone found in citrus fruits, under the
      oxidative stress and apoptosis induced by high levels of glucose in retinal
      ganglial cells (RGCs). RGC-5 cells were pretreated with hesperidin (12.5, 25, or
      50 MUmol/L) for 6 h followed by exposure to high (33.3 mmol/L) d-glucose for 48
      h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      was adopted to evaluate cell viability. Mitochondrial function was estimated by
      measuring the mitochondrial membrane potential (DeltaPsim). A fluorescent probe
      was employed to evaluate the intercellular production of reactive oxygen species
      (ROS). Colorimetric assay kits were used to evaluate lipid peroxidation,
      antioxidant enzyme activities, and protein carbonyls formation. The expression of
      apoptosis-related proteins and mitogen-activated protein kinase (MAPK) were
      measured with Western blotting. Hesperidin inhibited high glucose-mediated cell
      loss and restored mitochondrial function including a reversion of DeltaPsim loss
      and cytochrome c release. Treated with hesperidin, high glucose-induced increase
      in ROS, malondialdehyde, and protein carbonyl levels were blocked in RGC-5 cells.
      Hesperidin was found to elevate the activities of superoxide dismutase, catalase,
      glutathione peroxidase, and to recover glutathione levels. Hesperidin inhibited
      high glucose-induced cell apoptosis by attenuating the downregulation of caspase
      9, caspase-3, and Bax/Bcl-2. Furthermore, the phosphorylation of c-Jun N-terminal
      kinases (JNK) and p38 MAPK triggered by high glucose were attenuated in RGC-5
      cells after their incubation with hesperdin. We concluded that hesperidin may
      protect RGC-5 cells from high glucose-induced injury since it owns the properties
      of antioxidant action and blocks mitochondria-mediated apoptosis.

PMID- 29207477
TI  - A Robust Manifold Graph Regularized Nonnegative Matrix Factorization Algorithm
      for Cancer Gene Clustering.
AB  - Detecting genomes with similar expression patterns using clustering techniques
      plays an important role in gene expression data analysis. Non-negative matrix
      factorization (NMF) is an effective method for clustering the analysis of gene
      expression data. However, the NMF-based method is performed within the Euclidean
      space, and it is usually inappropriate for revealing the intrinsic geometric
      structure of data space. In order to overcome this shortcoming, Cai et al.
      proposed a novel algorithm, called graph regularized non-negative matrices
      factorization (GNMF). Motivated by the topological structure of the GNMF-based
      method, we propose improved graph regularized non-negative matrix factorization
      (GNMF) to facilitate the display of geometric structure of data space. Robust
      manifold non-negative matrix factorization (RM-GNMF) is designed for cancer gene
      clustering, leading to an enhancement of the GNMF-based algorithm in terms of
      robustness. We combine the l 2 , 1 -norm NMF with spectral clustering to conduct
      the wide-ranging experiments on the three known datasets. Clustering results
      indicate that the proposed method outperforms the previous methods, which
      displays the latest application of the RM-GNMF-based method in cancer gene
      clustering.

PMID- 29207478
TI  - Phenolic Content and Antioxidant Activity in Raw and Denatured Aqueous Extracts
      from Sprouts and Wheatgrass of Einkorn and Emmer Obtained under Salinity.
AB  - Total phenolic content (TPC), reducing power (RP), superoxide radical scavenging
      (RS), and thiobarbituric acid reactive substances (TBARS) production inhibition
      were measured in raw and denatured aqueous extracts from sprouts and wheatgrass
      of einkorn and emmer obtained at increasing salinity. Grains were incubated and
      kept at 0, 25, 50, and 100 mM NaCl until either sprout or wheatgrass stage.
      Additionally, a recovery treatment was included, in which sprouts obtained at 100
      mM NaCl were then transferred at 0 mM NaCl until wheatgrass stage. All parameters
      (TPC, RP, RS, and TBARS production inhibition) increased with sprouting and were
      highest in wheatgrass. Salinity increased all parameters, but the effect varied
      with NaCl concentration, genotype, developmental stage, and plant material
      processing (raw or denatured). Overall, given the delay and limitation of growth
      at high NaCl concentration, the best compromise appears to be the application of
      a moderate salinity (25 to 50 mM NaCl). In denatured extracts, TPC, RP, and RS
      slightly decreased, and TBARS was not affected, which means that antioxidant
      activity was mainly related to compounds other than enzymes and peptides, and
      thus it can be assumed to remain after digestion. Thus, supplementing the human
      diet with einkorn or emmer sprouts and wheatgrass can actually benefit health.

PMID- 29207479
TI  - Growth and Bone Mineralization of Very Preterm Infants at Term Corrected Age in
      Relation to Different Nutritional Intakes in the Early Postnatal Period.
AB  - Preterm infants often have a reduced bone mineral content (BMC) with increased
      risk of metabolic bone disease. After birth it is difficult to supply calcium
      (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not
      known whether high supplementation of minerals in the early postnatal period
      improves growth and bone mineralization. The aim of this study was to evaluate
      growth and bone mineralization at term corrected age (TCA) in very and extremely
      preterm infants who received different enteral Ca and P intakes during the first
      10 days of life. Infants (n = 109) with birth weights below 1500 g were randomly
      assigned to one of three groups that differed in the nutritional protocols
      delivered until day 10: Group A, mother's own milk (MOM) and donor milk
      (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM
      (start fortification >50 mL/day) and preterm formula. Due to the earlier
      commencement of fortification, Group C received higher intakes of calcium and
      phosphorus and protein (p < 0.001) until day 10. At TCA weight, length, BMC and
      bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not
      different between the groups. Nutritional intake of P was positively associated
      with length (beta; (95% confidence interval (CI): 0.20 (0.001; 0.393); p-value =
      0.048), whereas Ca intake was negatively associated with BMC (-1.94 (-2.78; 
      1.09); p-value < 0.001). A small interaction between Ca and P intake was only
      found for BMD (0.003 (0.00002; 0.00006); p-value = 0.036). The volume of human
      milk per kg provided during the first 10 days was positively associated with BMC
      (beta; (95% CI): 0.013 (0.002; 0.023); p < 0.017). Higher intakes of Ca and P
      during the first 10 days, as provided in this study, did not improve bone
      mineralization at term corrected age.

PMID- 29207480
TI  - Improved In Vivo Efficacy of Anti-Hypertensive Biopeptides Encapsulated in
      Chitosan Nanoparticles Fabricated by Ionotropic Gelation on Spontaneously
      Hypertensive Rats.
AB  - Recent biotechnological advances in the food industry have led to the enzymatic
      production of angiotensin I-converting enzyme (ACE)-inhibitory biopeptides with a
      strong blood pressure lowering effect from different food proteins. However, the
      safe oral administration of biopeptides is impeded by their enzymatic degradation
      due to gastrointestinal digestion. Consequently, nanoparticle (NP)-based delivery
      systems are used to overcome these gastrointestinal barriers to maintain the
      improved bioavailability and efficacy of the encapsulated biopeptides. In the
      present study, the ACE-inhibitory biopeptides were generated from stone fish
      (Actinopyga lecanora) protein using bromelain and stabilized by their
      encapsulation in chitosan (chit) nanoparticles (NPs). The nanoparticles were
      characterized for in vitro physicochemical properties and their antihypertensive
      effect was then evaluated on spontaneously hypertensive rats (SHRs). The results
      of a physicochemical characterization showed a small particle size of 162.70 nm,
      a polydispersity index (pdi) value of 0.28, a zeta potential of 48.78 mV, a high
      encapsulation efficiency of 75.36%, a high melting temperature of 146.78  degrees
      C and an in vitro sustained release of the biopeptides. The results of the in
      vivo efficacy indicated a dose-dependent blood pressure lowering effect of the
      biopeptide-loaded nanoparticles that was significantly higher (p < 0.05) compared
      with the un-encapsulated biopeptides. Moreover, the results of a morphological
      examination using transmission electron microscopy (TEM) demonstrated the
      nanoparticles as homogenous and spherical. Thus, the ACE-inhibitory biopeptides
      stabilized by chitosan nanoparticles can effectively reduce blood pressure for an
      extended period of time in hypertensive individuals.

PMID- 29207481
TI  - Switching between Successful and Dead-End Intermediates in Membrane Fusion.
AB  - Fusion of cellular membranes during normal biological processes, including
      proliferation, or synaptic transmission, is mediated and controlled by
      sophisticated protein machinery ensuring the preservation of the vital barrier
      function of the membrane throughout the process. Fusion of virus particles with
      host cell membranes is more sparingly arranged and often mediated by a single
      fusion protein, and the virus can afford to be less discriminative towards the
      possible different outcomes of fusion attempts. Formation of leaky intermediates
      was recently observed in some fusion processes, and an alternative trajectory of
      the process involving formation of pi-shaped structures was suggested. In this
      study, we apply the methods of elasticity theory and Lagrangian formalism
      augmented by phenomenological and molecular geometry constraints and boundary
      conditions to investigate the traits of this trajectory and the drivers behind
      the choice of one of the possible scenarios depending on the properties of the
      system. The alternative pathway proved to be a dead end, and, depending on the
      parameters of the participating membranes and fusion proteins, the system can
      either reversibly enter the corresponding "leaky" configuration or be trapped in
      it. A parametric study in the biologically relevant range of variables emphasized
      the fusion protein properties crucial for the choice of the fusion scenario.

PMID- 29207482
TI  - Physico-Chemical and Electrochemical Properties of Nanoparticulate NiO/C
      Composites for High Performance Lithium and Sodium Ion Battery Anodes.
AB  - Nanoparticulate NiO and NiO/C composites with different carbon proportions have
      been prepared for anode application in lithium and sodium ion batteries.
      Structural characterization demonstrated the presence of metallic Ni in the
      composites. Morphological study revealed that the NiO and Ni nanoparticles were
      well dispersed in the matrix of amorphous carbon. The electrochemical study
      showed that the lithium ion batteries (LIBs), containing composites with carbon,
      have promising electrochemical performances, delivering specific discharge
      capacities of 550 mAh/g after operating for 100 cycles at 1C. These excellent
      results could be explained by the homogeneity of particle size and structure, as
      well as the uniform distribution of NiO/Ni nanoparticles in the in situ generated
      amorphous carbon matrix. On the other hand, the sodium ion battery (NIB) with the
      NiO/C composite revealed a poor cycling stability. Post-mortem analyses revealed
      that this fact could be ascribed to the absence of a stable Solid Electrolyte
      Interface (SEI) or passivation layer upon cycling.

PMID- 29207483
TI  - Biochemical, Physiological and Transcriptomic Comparison between Burley and Flue
      Cured Tobacco Seedlings in Relation to Carbohydrates and Nitrate Content.
AB  - Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates
      high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant
      tumors in animals. Nitrate is a principle precursor of tobacco-specific
      nitrosamines. Nitrate content in burley tobacco was significantly higher than
      that in flue-cured tobacco. The present study investigated differences between
      the two tobacco types to explore the mechanisms of nitrate accumulation in burley
      tobacco. transcripts (3079) related to the nitrogen and carbon metabolism were
      observed. Expression of genes involved in carbon fixation, glucose and starch
      biosynthesis, nitrate translocation and assimilation were significantly low in
      burley tobacco than flue-cured tobacco. Being relative to flue-cured tobacco,
      burley tobacco was significantly lower at total nitrogen and carbohydrate
      content, nitrate reductase and glutamine synthetase activities, chlorophyll
      content and photosynthetic rate (Pn), but higher nitrate content. Burley tobacco
      required six-fold more nitrogen fertilizers than flue-cured tobacco, but both
      tobaccos had a similar leaf biomass. Reduced chlorophyll content and
      photosynthetic rate (Pn) might result in low carbohydrate formation, and low
      capacity of nitrogen assimilation and translocation might lead to nitrate
      accumulation in burley tobacco.

PMID- 29207484
TI  - Tunisian Milk Thistle: An Investigation of the Chemical Composition and the
      Characterization of Its Cold-Pressed Seed Oils.
AB  - In this study, milk thistle seeds growing in different areas in Tunisia were cold
      pressed and the extracted oils were examined for their chemical and antioxidant
      properties. The major fatty acids were linoleic acid (C18:2) (57.0%, 60.0%, and
      60.3% for the milk thistle seed oils native to Bizerte, Zaghouan and Sousse,
      respectively) and oleic acid (C18:1) (15.5%, 21.5%, and 22.4% for the milk
      thistle seed oils originating from Bizerte, Zaghouan and Sousse, respectively).
      High performance liquid chromatography (HPLC) analysis showed the richness of the
      milk thistle seed oils (MTSO) in alpha-tocopherol. The highest content was
      recorded for that of the region of Zaghouan (286.22 mg/kg). The total phenolic
      contents (TPC) of Zaghouan, Bizerte, and Sousse were 1.59, 8.12, and 4.73 Gallic
      Acid Equivalent (GAE) mg/g, respectively. Three phenolic acids were also
      identified (vanillic, p-coumaric, and silybine), with a predominance of the
      vanillic acid. The highest value was recorded for the Zaghouan milk thistle seed
      oil (83 mg/100 g). Differences in outcomes between regions may be due to climatic
      differences in areas. Zaghouan's cold-pressed milk thistle seed oil had a better
      quality than those of Bizerte and Sousse, and can be considered as a valuable
      source for new multi-purpose products or by-products for industrial, cosmetic,
      and pharmaceutical utilization.

PMID- 29207485
TI  - Study on the Ingredient Proportions and After-Treatment of Laser Sintering Walnut
      Shell Composites.
AB  - To alleviate resource shortage, reduce the cost of materials consumption and the
      pollution of agricultural and forestry waste, walnut shell composites (WSPC)
      consisting of walnut shell as additive and copolyester hot melt adhesive (Co-PES)
      as binder was developed as the feedstock of selective laser sintering (SLS). WSPC
      parts with different ingredient proportions were fabricated by SLS and processed
      through after-treatment technology. The density, mechanical properties and
      surface quality of WSPC parts before and after post processing were analyzed via
      formula method, mechanical test and scanning electron microscopy (SEM),
      respectively. Results show that, when the volume fraction of the walnut shell
      powder in the WSPC reaches the maximum (40%), sintered WSPC parts have the
      smallest warping deformation and the highest dimension precision, although the
      surface quality, density, and mechanical properties are low. However, performing
      permeating resin as the after-treatment technology could considerably increase
      the tensile, bending and impact strength by 496%, 464%, and 516%, respectively.

PMID- 29207486
TI  - Superior Stability of Hydroxysafflor Yellow A in Xuebijing Injection and the
      Associated Mechanism.
AB  - Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection.
      At first, the stability of HSYA in solution and in a Xuebijing injection was
      investigated, then the mechanisms of the increased stability of HSYA in the XBJ
      injection were investigated to provide useful information on clinical safety.
      HSYA stability was investigated as a function of pH and temperature in aqueous
      solution and an XBJ injection, following the guidelines from the International
      Conference on Harmonisation of Technical Requirements for Registration of
      Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA
      reaction followed first-order kinetics under all conditions. The half-life of
      HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation
      energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53
      and 92.90 kJ?mol-1 by using Arrhenius equation. The results indicated that HSYA
      was more stable in XBJ than in aqueous solution. Two products were identified and
      the mechanism was intra-molecular nucleophilic substitution. The excellent
      stability of HSYA in XBJ injection partly due to the micelles formed in the
      injection. The study may provide clues for compatibility in TCM prescription and
      also provide useful information for further preparation technology research of
      HSYA and assessment of clinical safety of XBJ.

PMID- 29207488
TI  - A Wideband Magnetoresistive Sensor for Monitoring Dynamic Fault Slip in
      Laboratory Fault Friction Experiments.
AB  - A non-contact, wideband method of sensing dynamic fault slip in laboratory
      geophysical experiments employs an inexpensive magnetoresistive sensor, a small
      neodymium rare earth magnet, and user built application-specific wideband signal
      conditioning. The magnetoresistive sensor generates a voltage proportional to the
      changing angles of magnetic flux lines, generated by differential motion or
      rotation of the near-by magnet, through the sensor. The performance of an array
      of these sensors compares favorably to other conventional position sensing
      methods employed at multiple locations along a 2 m long * 0.4 m deep laboratory
      strike-slip fault. For these magnetoresistive sensors, the lack of resonance
      signals commonly encountered with cantilever-type position sensor mounting, the
      wide band response (DC to ~ 100 kHz) that exceeds the capabilities of many
      traditional position sensors, and the small space required on the sample, make
      them attractive options for capturing high speed fault slip measurements in these
      laboratory experiments. An unanticipated observation of this study is the
      apparent sensitivity of this sensor to high frequency electomagnetic signals
      associated with fault rupture and (or) rupture propagation, which may offer new
      insights into the physics of earthquake faulting.

PMID- 29207487
TI  - Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review.
AB  - Traumatic brain injury (TBI) is one of the world's leading causes of morbidity
      and mortality among young individuals. TBI applies powerful rotational and
      translational forces to the brain parenchyma, which results in a traumatic
      diffuse axonal injury (DAI) responsible for brain swelling and neuronal death.
      Following TBI, axonal degeneration has been identified as a progressive process
      that starts with disrupted axonal transport causing axonal swelling, followed by
      secondary axonal disconnection and Wallerian degeneration. These modifications in
      the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing
      the gradual gathering of transport products so as to generate axonal swellings
      and modifications in neuronal homeostasis. Oxidative stress with consequent
      impairment of endogenous antioxidant defense mechanisms plays a significant role
      in the secondary events leading to neuronal death. Studies support the role of an
      altered axonal calcium homeostasis as a mechanism in the secondary damage of
      axon, and suggest that calcium channel blocker can alleviate the secondary
      damage, as well as other mechanisms implied in the secondary injury, and could be
      targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)
      mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in
      the defense mechanisms through the use of exogenous antioxidants may be
      neuroprotective, particularly if they are given within the neuroprotective time
      window. A promising potential therapeutic target for DAI is to directly address
      mitochondria-related injury or to modulate energetic axonal energy failure.

PMID- 29207489
TI  - Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-kappaB
      Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-alpha and
      the Fas Ligand.
AB  - Quinacrine has been used for therapeutic drugs in some clinical settings. In the
      present study, we demonstrated that quinacrine decreased the expression of
      intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor (TNF)
      alpha and interleukin-1 (IL-1) alpha in human lung adenocarcinoma A549 cells.
      Quinacrine inhibited ICAM-1 mRNA expression and nuclear factor kappaB (NF-kappaB)
      responsive luciferase reporter activity following a treatment with TNF-alpha and
      IL-1alpha. In the NF-kappaB signaling pathway, quinacrine did not markedly affect
      the TNF-alpha-induced degradation of the inhibitor of NF-kappaB or the TNF-alpha
      induced phosphorylation of the NF-kappaB subunit, p65, at Ser-536 and its
      subsequent translocation to the nucleus. In contrast, a chromatin
      immunoprecipitation assay showed that quinacrine prevented the binding of p65 to
      the ICAM-1 promoter following TNF-alpha stimulation. Moreover, TNF-alpha and the
      Fas ligand effectively reduced the viability of A549 cells in the presence of
      quinacrine only. Quinacrine down-regulated the constitutive and TNF-alpha-induced
      expression of c-FLIP and Mcl-1 in A549 cells. These results revealed that
      quinacrine inhibits ICAM-1 transcription by blocking the DNA binding of p65 and
      sensitizes A549 cells to TNF-alpha and the Fas ligand.

PMID- 29207490
TI  - Is Trabecular Bone Score Valuable in Bone Microstructure Assessment after Gastric
      Bypass in Women with Morbid Obesity?
AB  - INTRODUCTION: The effects of bariatric surgery on skeletal health raise many
      concerns. Trabecular bone score (TBS) is obtained through the analysis of lumbar
      spine dual X-ray absorptiometry (DXA) images and allows an indirect assessment of
      skeletal microarchitecture (MA). The aim of our study was to evaluate the changes
      in bone mineral density (BMD) and alterations in bone microarchitecture assessed
      by TBS in morbidly obese women undergoing Roux-en-Y gastric bypass (RYGB), over a
      three-year follow-up. MATERIAL/METHODS: A prospective study of 38 morbidly obese
      white women, aged 46.3 +/- 8.2 years, undergoing RYGB was conducted. Biochemical
      analyses and DXA scans with TBS evaluation were performed before and at one year
      and three years after surgery. RESULTS: Patients showed normal calcium and
      phosphorus plasma concentrations throughout the study. However, 25-hydroxyvitamin
      D (25(OH)D3) decreased, and 71% of patients had a vitamin D deficiency at three
      years. BMD at femoral neck and lumbar spine (LSBMD) significantly decreased 13.53
      +/- 5.42% and 6.03 +/- 6.79%, respectively, during the three-year follow-up;
      however Z-score values remained above those for women of the same age. TBS was
      within normal ranges at one and three years (1.431 +/- 106 and 1.413 +/- 85,
      respectively), and at the end of the study, 73.7% of patients had normal bone MA.
      TBS at three years correlated inversely with age (r = -0.41, p = 0.010), body fat
      (r = -0.465, p = 0.004) and greater body fat deposited in trunk (r = -0.48, p =
      0.004), and positively with LSBMD (r = 0.433, p = 0.007), fat mass loss (r =
      0.438, p = 0.007) and lean mass loss (r = 0.432, p = 0.008). In the regression
      analysis, TBS remained associated with body fat (beta = -0.625, p = 0.031; R2 =
      0.47). The fracture risk, calculated by FRAX(r) (University of Sheffield,
      Sheffield, UK), with and without adjustment by TBS, was low. CONCLUSION: Women
      undergoing RYGB in the mid-term have a preserved bone MA, assessed by TBS.

PMID- 29207491
TI  - Dietary Intake of High-Protein Foods and Other Major Foods in Meat-Eaters,
      Poultry-Eaters, Fish-Eaters, Vegetarians, and Vegans in UK Biobank.
AB  - Vegetarian diets are defined by the absence of meat and fish, but differences in
      the intake of other foods between meat-eaters and low or non-meat eaters are also
      important to document. We examined intakes of high-protein foods (meat, poultry,
      fish, legumes, nuts, vegetarian protein alternatives, dairy products, and eggs)
      and other major food groups (fruit, vegetables, bread, pasta, rice, snack foods,
      and beverages) in regular meat-eaters, low meat-eaters, poultry-eaters, fish
      eaters, vegetarians, and vegans of white ethnicity participating in UK Biobank
      who had completed at least one web-based 24-h dietary assessment (n = 199,944).
      In regular meat-eaters, around 25% of total energy came from meat, fish, dairy
      and plant milk, cheese, yogurt, and eggs. In vegetarians, around 20% of energy
      came from dairy and plant milk, cheese, yoghurt, eggs, legumes, nuts, and
      vegetarian protein alternatives, and in vegans around 15% came from plant milk,
      legumes, vegetarian alternatives, and nuts. Low and non-meat eaters had higher
      intakes of fruit and vegetables and lower intakes of roast or fried potatoes
      compared to regular meat-eaters. The differences in the intakes of meat, plant
      based high-protein foods, and other foods between meat-eaters and low and non
      meat eaters in UK Biobank may contribute to differences in health outcomes.

PMID- 29207492
TI  - Rapid Non-Enzymatic Glycation of the Insulin Receptor under Hyperglycemic
      Conditions Inhibits Insulin Binding In Vitro: Implications for Insulin
      Resistance.
AB  - The causes of insulin resistance are not well-understood in either type 1 or type
      2 diabetes. Insulin (INS) is known to undergo rapid non-enzymatic covalent
      conjugation to glucose or other sugars (glycation). Because the insulin receptor
      (IR) has INS-like regions associated with both glucose and INS binding, we
      hypothesize that hyperglycemic conditions may rapidly glycate the IR, chronically
      interfering with INS binding. IR peptides were synthesized spanning IR-
      associated INS-binding regions. Glycation rates of peptides under hyperglycemic
      conditions were followed over six days using matrix assisted laser
      desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. INS
      conjugated to horse-radish peroxidase was used to determine INS binding to IR
      peptides in glycated and non-glycated forms. Several IR peptides were glycated up
      to 14% within days of exposure to 20-60 mM glucose. Rates of IR-peptide glycation
      were comparable to those of insulin. Glycation of four IR peptides significantly
      inhibits INS binding to them. Glycation of intact IR also decreases INS binding
      by about a third, although it was not possible to confirm the glycation sites on
      the intact IR. Glycation of the IR may therefore provide a mechanism by which INS
      resistance develops in diabetes. Demonstration of glycation of intact IR in vivo
      is needed.

PMID- 29207493
TI  - Glycoprotein 90K Promotes E-Cadherin Degradation in a Cell Density-Dependent
      Manner via Dissociation of E-Cadherin-p120-Catenin Complex.
AB  - Glycoprotein 90K (also known as LGALS3BP or Mac-2BP) is a tumor-associated
      protein, and high 90K levels are associated with poor prognosis in some cancers.
      To clarify the role of 90K as an indicator for poor prognosis and metastasis in
      epithelial cancers, the present study investigated the effect of 90K on an
      adherens junctional protein, E-cadherin, which is frequently absent or
      downregulated in human epithelial cancers. Treatment of certain cancer cells with
      90K significantly reduced E-cadherin levels in a cell-population-dependent
      manner, and these cells showed decreases in cell adhesion and increases in
      invasive cell motility. Mechanistically, 90K-induced E-cadherin downregulation
      occurred via ubiquitination-mediated proteasomal degradation. 90K interacted with
      the E-cadherin-p120-catenin complex and induced its dissociation, altering the
      phosphorylation status of p120-catenin, whereas it did not associate with beta
      catenin. In subconfluent cells, 90K decreased membrane-localized p120-catenin and
      the membrane fraction of the p120-catenin. Particularly, 90K-induced E-cadherin
      downregulation was diminished in p120-catenin knocked-down cells. Taken together,
      90K upregulation promotes the dissociation of the E-cadherin-p120-catenin
      complex, leading to E-cadherin proteasomal degradation, and thereby destabilizing
      adherens junctions in less confluent tumor cells. Our results provide a potential
      mechanism to explain the poor prognosis of cancer patients with high serum 90K
      levels.

PMID- 29207494
TI  - An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory
      Syndrome Coronavirus.
AB  - The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV
      HKU1, some of which have been known for decades. The severe acute respiratory
      syndrome (SARS) CoV briefly emerged into the human population but was controlled.
      In 2012, another novel severely human pathogenic CoV-the Middle East Respiratory
      Syndrome (MERS)-CoV-was identified in the Kingdom of Saudi Arabia; 80% of over
      2000 human cases have been recorded over five years. Targeted research remains
      key to developing control strategies for MERS-CoV, a cause of mild illness in its
      camel reservoir. A new therapeutic toolbox being developed in response to MERS is
      also teaching us more about how CoVs cause disease. Travel-related cases continue
      to challenge the world's surveillance and response capabilities, and more data
      are needed to understand unexplained primary transmission. Signs of genetic
      change have been recorded, but it remains unclear whether there is any impact on
      clinical disease. How camels came to carry the virus remains academic to the
      control of MERS. To date, human-to-human transmission has been inefficient, but
      virus surveillance, characterisation, and reporting are key to responding to any
      future change. MERS-CoV is not currently a pandemic threat; it is spread mainly
      with the aid of human habit and error.

PMID- 29207496
TI  - Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for
      Optimal Bactericidal Activity.
AB  - Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid
      bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D
      (Gr) yielding optimal and broadened bactericidal activity against both
      Escherichia coli and Staphylococcus aureus. The adsorption of DODAB/Gr bilayer
      onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm,
      changed the zeta-potential of the NPs from negative to positive, and yielded a
      narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and
      maximal microbicidal activity at very small concentrations of the antimicrobials,
      namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized
      the advantages of highly-organized, nanostructured, and cationic particles to
      achieve hybrid combinations of antimicrobials with broad spectrum activity at
      considerably reduced DODAB and Gr concentrations.

PMID- 29207495
TI  - Validity of Dietary Assessment in Athletes: A Systematic Review.
AB  - Dietary assessment methods that are recognized as appropriate for the general
      population are usually applied in a similar manner to athletes, despite the
      knowledge that sport-specific factors can complicate assessment and impact
      accuracy in unique ways. As dietary assessment methods are used extensively
      within the field of sports nutrition, there is concern the validity of
      methodologies have not undergone more rigorous evaluation in this unique
      population sub-group. The purpose of this systematic review was to compare two or
      more methods of dietary assessment, including dietary intake measured against
      biomarkers or reference measures of energy expenditure, in athletes. Six
      electronic databases were searched for English-language, full-text articles
      published from January 1980 until June 2016. The search strategy combined the
      following keywords: diet, nutrition assessment, athlete, and validity; where the
      following outcomes are reported but not limited to: energy intake, macro and/or
      micronutrient intake, food intake, nutritional adequacy, diet quality, or
      nutritional status. Meta-analysis was performed on studies with sufficient
      methodological similarity, with between-group standardized mean differences (or
      effect size) and 95% confidence intervals (CI) being calculated. Of the 1624
      studies identified, 18 were eligible for inclusion. Studies comparing self
      reported energy intake (EI) to energy expenditure assessed via doubly labelled
      water were grouped for comparison (n = 11) and demonstrated mean EI was under
      estimated by 19% (-2793 +/- 1134 kJ/day). Meta-analysis revealed a large pooled
      effect size of -1.006 (95% CI: -1.3 to -0.7; p < 0.001). The remaining studies (n
      = 7) compared a new dietary tool or instrument to a reference method(s) (e.g.,
      food record, 24-h dietary recall, biomarker) as part of a validation study. This
      systematic review revealed there are limited robust studies evaluating dietary
      assessment methods in athletes. Existing literature demonstrates the substantial
      variability between methods, with under- and misreporting of intake being
      frequently observed. There is a clear need for careful validation of dietary
      assessment methods, including emerging technical innovations, among athlete
      populations.

PMID- 29207497
TI  - Accumulation of De-Icing Salt and Leaching in Spanish Soils Surrounding Roadways.
AB  - The environmental implications of soil salinity caused by accumulation of de
      icing salt and leaching in soils of northeastern Spain were examined. For this
      purpose, the concentrations of ions associated with diagnosing and managing this
      problem were evaluated from several measurements performed over one year along a
      road. This analysis demonstrated a higher concentration of soluble Na+ in the
      soil 3 m from a road in the northernmost part of the study area in February,
      which made the soil saline-sodic. Data from the rest of the study period (during
      the spring and summer) demonstrated that the de-icing salt moved to areas farther
      south by runoff water, which caused environmental impacts by modifying soil
      characteristics. These results suggest that leaching of Ca2+ and Mg2+ cations
      occurred faster in the studied systems in sodic soils. Leaching of these cations
      may affect plant yield, and results in environmental impacts within 3-30 m from
      the road. Awareness of this impact will be useful for developing future
      strategies for evaluating and reporting these complex relationships within
      Spain's transport system and environment.

PMID- 29207498
TI  - Steppogenin Isolated from Cudrania tricuspidata Shows Antineuroinflammatory
      Effects via NF-kappaB and MAPK Pathways in LPS-Stimulated BV2 and Primary Rat
      Microglial Cells.
AB  - Excessive microglial stimulation has been recognized in several neurodegenerative
      diseases, including Parkinson's disease (PD), Alzheimer's disease (AD),
      amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple
      sclerosis (MS), and stroke. When microglia are stimulated, they produce
      proinflammatory mediators and cytokines, including nitric oxide (NO) derived from
      inducible NO synthase (iNOS), prostaglandin E2 (PGE2) derived from cyclooxygenase
      2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions
      are related to the nuclear factor-kappa B (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-kappaB
      and MAPK is vital to prevent microglial activation and confer resistance against
      neuronal injury. In this study, steppogenin (1) isolated from Cudrania
      tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide
      (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and
      cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover,
      western blot analysis and immunofluorescence revealed that the nuclear
      translocation of NF-kappaB was inhibited in LPS-induced BV2 and rat primary
      microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial
      cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2
      terminal kinase (JNK) and p38 MAPK signaling. These results suggested that
      steppogenin (1) exerted antineuroinflammatory effects against acute
      neuroinflammation in BV2 and rat primary microglial cells by suppressing the
      activation of NF-kappaB and MAPK signaling and the production of proinflammatory
      mediators and cytokines.

PMID- 29207499
TI  - Sulfur-Mediated-Alleviation of Aluminum-Toxicity in Citrus grandis Seedlings.
AB  - Limited data are available on the sulfur (S)-mediated-alleviation of aluminum
      (Al)-toxicity in higher plants. Citrus grandis seedlings were irrigated for 18
      weeks with 0.5 mM MgSO4 or 0.5 mM MgSO4 + 0.5 mM Na2SO4, and 0 (-Al) or 1 mM
      AlCl3.6H2O (+Al, Al-toxicity). Under Al-toxicity, S decreased the level of Al in
      leaves; increased the relative water content (RWC) of roots and leaves, the
      contents of phosphorus (P), calcium (Ca) and magnesium (Mg) per plant, the dry
      weights (DW) of roots and shoots, the ratios of root DW/shoot DW, and the Al
      induced secretion of citrate from root; and alleviated the Al-induced inhibition
      of photosynthesis via mitigating the Al-induced decrease of electron transport
      capacity resulting from the impaired photosynthetic electron transport chain. In
      addition to decreasing the Al-stimulated H2O2 production, the S-induced
      upregulation of both S metabolism-related enzymes and antioxidant enzymes also
      contributed to the S-mediated-alleviation of oxidative damage in Al-treated roots
      and leaves. Decreased transport of Al from roots to shoots and relatively little
      accumulation of Al in leaves, and increased leaf and root RWC and P, Ca, and Mg
      contents per plant might also play a role in the S-mediated-alleviation of Al
      toxicity.

PMID- 29207500
TI  - Enrichment of Circular Code Motifs in the Genes of the Yeast Saccharomyces
      cerevisiae.
AB  - A set X of 20 trinucleotides has been found to have the highest average
      occurrence in the reading frame, compared to the two shifted frames, of genes of
      bacteria, archaea, eukaryotes, plasmids and viruses. This set X has an
      interesting mathematical property, since X is a maximal C3 self-complementary
      trinucleotide circular code. Furthermore, any motif obtained from this circular
      code X has the capacity to retrieve, maintain and synchronize the original
      (reading) frame. Since 1996, the theory of circular codes in genes has mainly
      been developed by analysing the properties of the 20 trinucleotides of X, using
      combinatorics and statistical approaches. For the first time, we test this theory
      by analysing the X motifs, i.e., motifs from the circular code X, in the complete
      genome of the yeast Saccharomyces cerevisiae. Several properties of X motifs are
      identified by basic statistics (at the frequency level), and evaluated by
      comparison to R motifs, i.e., random motifs generated from 30 different random
      codes R. We first show that the frequency of X motifs is significantly greater
      than that of R motifs in the genome of S. cerevisiae. We then verify that no
      significant difference is observed between the frequencies of X and R motifs in
      the non-coding regions of S. cerevisiae, but that the occurrence number of X
      motifs is significantly higher than R motifs in the genes (protein-coding
      regions). This property is true for all cardinalities of X motifs (from 4 to 20)
      and for all 16 chromosomes. We further investigate the distribution of X motifs
      in the three frames of S. cerevisiae genes and show that they occur more
      frequently in the reading frame, regardless of their cardinality or their length.
      Finally, the ratio of X genes, i.e., genes with at least one X motif, to non-X
      genes, in the set of verified genes is significantly different to that observed
      in the set of putative or dubious genes with no experimental evidence. These
      results, taken together, represent the first evidence for a significant
      enrichment of X motifs in the genes of an extant organism. They raise two
      hypotheses: the X motifs may be evolutionary relics of the primitive codes used
      for translation, or they may continue to play a functional role in the complex
      processes of genome decoding and protein synthesis.

PMID- 29207501
TI  - Detection of a Planktothrix agardhii Bloom in Portuguese Marine Coastal Waters.
AB  - Cyanobacteria blooms are frequent in freshwaters and are responsible for water
      quality deterioration and human intoxication. Although, not a new phenomenon,
      concern exists on the increasing persistence, scale, and toxicity of these
      blooms. There is evidence, in recent years, of the transfer of these toxins from
      inland to marine waters through freshwater outflow. However, the true impact of
      these blooms in marine habitats has been overlooked. In the present work, we
      describe the detection of Planktothrix agardhii, which is a common microcystin
      producer, in the Portuguese marine coastal waters nearby a river outfall in an
      area used for shellfish harvesting and recreational activities. P. agardhii was
      first observed in November of 2016 in seawater samples that are in the scope of
      the national shellfish monitoring system. This occurrence was followed closely
      between November and December of 2016 by a weekly sampling of mussels and water
      from the sea pier and adjacent river mouth with salinity ranging from 35 to 3.
      High cell densities were found in the water from both sea pier and river outfall,
      reaching concentrations of 4,960,608 cells.L-1 and 6810.3 * 106 cells.L-1
      respectively. Cultures were also established with success from the environment
      and microplate salinity growth assays showed that the isolates grew at salinity
      10. HPLC-PDA analysis of total microcystin content in mussel tissue, water
      biomass, and P. agardhii cultures did not retrieve a positive result. In
      addition, microcystin related genes were not detected in the water nor cultures.
      So, the P. agardhii present in the environment was probably a non-toxic strain.
      This is, to our knowledge, the first report on a P. agardhii bloom reaching the
      sea and points to the relevance to also monitoring freshwater harmful
      phytoplankton and related toxins in seafood harvesting and recreational coastal
      areas, particularly under the influence of river plumes.

PMID- 29207502
TI  - Relationship between Vitamin Intake and Depressive Symptoms in Elderly Japanese
      Individuals: Differences with Gender and Body Mass Index.
AB  - Only a few studies have focused on the relationship between vitamin intake and
      depressive symptoms in Japanese individuals. This cross-sectional study
      investigated the relationship between vitamin intake and depressive symptoms in
      1634 elderly Japanese individuals (65 years and older). The consumption of
      fifteen vitamins including retinol, a retinol equivalent, beta-carotene
      equivalent, vitamin D, alpha-tocopherol, vitamin K, vitamin group B, vitamin C,
      and cryptoxanthine was analyzed using a brief-type self-administered diet history
      questionnaire (BDHQ). The short version of the Geriatric Depression Scale (GDS)
      was used to assess depressive symptoms. The prevalence of participants with
      depressive symptoms was 26.7%. The consumption of all vitamins, except for
      retinol and vitamin D, was lower among depressed than non-depressed participants.
      The consumption of vitamins was significantly less in female and overweight
      participants with depressive symptoms than in elderly participants without
      depressive symptoms. After adjustments for potential confounders, none of the
      fifteen vitamins were correlated with depressive symptoms in male or underweight
      participants. Associations between vitamin deficiencies and depressive symptoms
      were observed in female and overweight elderly participants. Our findings
      demonstrated a relationship between vitamin intake and depressive symptoms.

PMID- 29207504
TI  - Effect of Anisotropy on the Resilient Behaviour of a Granular Material in Low
      Traffic Pavement.
AB  - Granular materials are often used in pavement structures. The influence of
      anisotropy on the mechanical behaviour of granular materials is very important.
      The coupled effects of water content and fine content usually lead to more
      complex anisotropic behaviour. With a repeated load triaxial test (RLTT), it is
      possible to measure the anisotropic deformation behaviour of granular materials.
      This article initially presents an experimental study of the resilient repeated
      load response of a compacted clayey natural sand with three fine contents and
      different water contents. Based on anisotropic behaviour, the non-linear
      resilient model (Boyce model) is improved by the radial anisotropy coefficient
      gamma3 instead of the axial anisotropy coefficient gamma1. The results from both
      approaches (gamma1 and gamma3) are compared with the measured volumetric and
      deviatoric responses. These results confirm the capacity of the improved model to
      capture the general trend of the experiments. Finally, finite element
      calculations are performed with CAST3M in order to validate the improvement of
      the modified Boyce model (from gamma1 to gamma3). The modelling results indicate
      that the modified Boyce model with gamma3 is more widely available in different
      water contents and different fine contents for this granular material. Besides,
      based on the results, the coupled effects of water content and fine content on
      the deflection of the structures can also be observed.

PMID- 29207503
TI  - Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2
      Protein Using Quantitative Differential Proteomics.
AB  - Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in
      pediatric populations globally. This study examined proteomic profile changes in
      A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain
      binding motif(s) in the M2-2 protein. These motifs are involved in the
      interruption of antiviral signaling, namely the interaction between the TNF
      receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS)
      proteins. The aim of this study was to provide insight into the overall and novel
      impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem
      mass tagging, stable isotope labeling, and high-resolution mass spectrometry were
      used for quantitative proteomic analysis. Using quantitative proteomics and Venn
      analysis, 1248 common proteins were detected in all infected samples of both
      technical sets. Hierarchical clustering of the differentiated proteome displayed
      distinct proteomic signatures that were controlled by the motif(s).
      Bioinformatics and experimental analysis confirmed the differentiated proteomes,
      revealed novel cellular biological events, and implicated key pathways controlled
      by hMPV M2-2 PDZ domain-binding motif(s). This provides further insight for
      evaluating M2-2 mutants as potent vaccine candidates.

PMID- 29207505
TI  - Co-Precipitation, Strength and Electrical Resistivity of Cu-26 wt % Ag-0.1 wt %
      Fe Alloy.
AB  - Both a Cu-26 wt % Ag (Fe-free) alloy and Cu-26 wt % Ag-0.1 wt % Fe (Fe-doping)
      alloy were subjected to different heat treatments. We studied the precipitation
      kinetics of Ag and Cu, microstructure evolution, magnetization, hardness,
      strength, and electrical resistivity of the two alloys. Fe addition was incapable
      of changing the precipitation kinetics of Ag and Cu; however, it decreased the
      size and spacing of rod-shaped Ag precipitates within a Cu matrix, because Fe
      might affect the elastic strain field and diffusion field, suppressing the
      nucleation of Ag precipitates. Magnetization curves showed that gamma-Fe
      precipitates were precipitated out of the Cu matrix, along with Ag precipitates
      in Fe-doping alloy after heat treatments. The yield strength of the Fe-doping
      alloy was higher than that of the Fe-free alloy, and the maximum increment was
      about 41.3%. The electrical conductivity in the aged Fe-doping alloy was up to
      about 67% IACS (International Annealed Copper Standard). Hardness, strength, and
      electrical resistivity were intensively discussed, based on the microstructural
      characterization and solute contributions of both alloys. Our results
      demonstrated that an increasing fraction of nanoscale gamma-Fe precipitates and
      decreasing spacing between Ag precipitates resulted in the increasing strength of
      the Fe-doping alloy.

PMID- 29207506
TI  - Longitudinal Surveillance of Porcine Rotavirus B Strains from the United States
      and Canada and In Silico Identification of Antigenically Important Sites.
AB  - Rotavirus B (RVB) is an important swine pathogen, but control and prevention
      strategies are limited without an available vaccine. To develop a subunit RVB
      vaccine with maximal effect, we characterized the amino acid sequence variability
      and predicted antigenicity of RVB viral protein 7 (VP7), a major neutralizing
      antibody target, from clinically infected pigs in the United States and Canada.
      We identified genotype-specific antigenic sites that may be antibody
      neutralization targets. While some antigenic sites had high amino acid functional
      group diversity, nine antigenic sites were completely conserved. Analysis of
      nucleotide substitution rates at amino acid sites (dN/dS) suggested that negative
      selection appeared to be playing a larger role in the evolution of the identified
      antigenic sites when compared to positive selection, and was identified in six of
      the nine conserved antigenic sites. These results identified important
      characteristics of RVB VP7 variability and evolution and suggest antigenic
      residues on RVB VP7 that are negatively selected and highly conserved may be good
      candidate regions to include in a subunit vaccine design due to their tendency to
      remain stable.

PMID- 29207507
TI  - Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl,
      Abamectin, and Their Mixture in Male Rats.
AB  - Exposure to mixtures of toxicants (e.g., pesticides) is common in real life and a
      subject of current concern. The present investigation was undertaken to assess
      some toxicological effects in male rats following exposure to methomyl (MET),
      abamectin (ABM), and their combination (MET+ABM), and to evaluate the
      ameliorative effect of zinc co-administration. Three groups of rats were
      designated for MET, ABM, and the mixture treatments. Three other groups were
      designated for zinc in conjunction with the pesticides. Additionally, one group
      received water only (control), and the other represented a positive zinc
      treatment. The obtained results revealed that MET was acutely more toxic than
      ABM. The tested pesticides induced significant elevation in lipid peroxidation
      and catalase levels, while declined the levels of the other tested parameters
      e.g., Superoxide dismutase (SOD), Glutathione-S-transferase (GST), Glutathione
      peroxidase (GPx), Glutathione reductase (GR), Cytochrome P450 (CYP450),
      testosterone, and thyroxine). Biochemical alterations induced by the mixture were
      greater than those recorded for each of the individual insecticides. The joint
      action analysis, based on the obtained biochemical data, revealed the dominance
      of antagonistic action among MET and ABM. Zinc supplementation achieved
      noticeable ameliorative effects. It was concluded that zinc may act as a powerful
      antioxidant, especially in individuals who are occupationally exposed daily to
      low doses of such pesticides.

PMID- 29207509
TI  - A Round-Efficient Authenticated Key Agreement Scheme Based on Extended Chaotic
      Maps for Group Cloud Meeting.
AB  - The security is a critical issue for business purposes. For example, the cloud
      meeting must consider strong security to maintain the communication privacy.
      Considering the scenario with cloud meeting, we apply extended chaotic map to
      present passwordless group authentication key agreement, termed as Passwordless
      Group Authentication Key Agreement (PL-GAKA). PL-GAKA improves the computation
      efficiency for the simple group password-based authenticated key agreement
      (SGPAKE) proposed by Lee et al. in terms of computing the session key. Since the
      extended chaotic map has equivalent security level to the Diffie-Hellman key
      exchange scheme applied by SGPAKE, the security of PL-GAKA is not sacrificed when
      improving the computation efficiency. Moreover, PL-GAKA is a passwordless scheme,
      so the password maintenance is not necessary. Short-term authentication is
      considered, hence the communication security is stronger than other protocols by
      dynamically generating session key in each cloud meeting. In our analysis, we
      first prove that each meeting member can get the correct information during the
      meeting. We analyze common security issues for the proposed PL-GAKA in terms of
      session key security, mutual authentication, perfect forward security, and data
      integrity. Moreover, we also demonstrate that communicating in PL-GAKA is secure
      when suffering replay attacks, impersonation attacks, privileged insider attacks,
      and stolen-verifier attacks. Eventually, an overall comparison is given to show
      the performance between PL-GAKA, SGPAKE and related solutions.

PMID- 29207508
TI  - Preparation of A Spaceflight: Apoptosis Search in Sutured Wound Healing Models.
AB  - To prepare the ESA (European Space Agency) spaceflight project "Wound healing and
      Sutures in Unloading Conditions", we studied mechanisms of apoptosis in wound
      healing models based on ex vivo skin tissue cultures, kept for 10 days alive in
      serum-free DMEM/F12 medium supplemented with bovine serum albumin,
      hydrocortisone, insulin, ascorbic acid and antibiotics at 32  degrees C. The
      overall goal is to test: (i) the viability of tissue specimens; (ii) the gene
      expression of activators and inhibitors of apoptosis and extracellular matrix
      components in wound and suture models; and (iii) to design analytical protocols
      for future tissue specimens after post-spaceflight download. Hematoxylin-Eosin
      and Elastica-van-Gieson staining showed a normal skin histology with no signs of
      necrosis in controls and showed a normal wound suture. TdT-mediated dUTP-biotin
      nick end labeling for detecting DNA fragmentation revealed no significant
      apoptosis. No activation of caspase-3 protein was detectable. FASL, FADD, CASP3,
      CASP8, CASP10, BAX, BCL2, CYC1, APAF1, LAMA3 and SPP1 mRNAs were not altered in
      epidermis and dermis samples with and without a wound compared to 0 day samples
      (specimens investigated directly post-surgery). BIRC5, CASP9, and FN1 mRNAs were
      downregulated in epidermis/dermis samples with and/or without a wound compared to
      0 day samples. BIRC2, BIRC3 were upregulated in 10 day wound samples compared to
      0 day samples in epidermis/dermis. RELA/FAS mRNAs were elevated in 10 day wound
      and no wound samples compared to 0 day samples in dermis. In conclusion, we
      demonstrate that it is possible to maintain live skin tissue cultures for 10
      days. The viability analysis showed no significant signs of cell death in wound
      and suture models. The gene expression analysis demonstrated the interplay of
      activators and inhibitors of apoptosis and extracellular matrix components,
      thereby describing important features in ex vivo sutured wound healing models.
      Collectively, the performed methods defining analytical protocols proved to be
      applicable for post-flight analyzes of tissue specimens after sample return.

PMID- 29207510
TI  - A Combined Approach of Sensor Data Fusion and Multivariate Geostatistics for
      Delineation of Homogeneous Zones in an Agricultural Field.
AB  - To assess spatial variability at the very fine scale required by Precision
      Agriculture, different proximal and remote sensors have been used. They provide
      large amounts and different types of data which need to be combined. An
      integrated approach, using multivariate geostatistical data-fusion techniques and
      multi-source geophysical sensor data to determine simple summary scale-dependent
      indices, is described here. These indices can be used to delineate management
      zones to be submitted to differential management. Such a data fusion approach
      with geophysical sensors was applied in a soil of an agronomic field cropped with
      tomato. The synthetic regionalized factors determined, contributed to split the
      3D edaphic environment into two main horizontal structures with different
      hydraulic properties and to disclose two main horizons in the 0-1.0-m depth with
      a discontinuity probably occurring between 0.40 m and 0.70 m. Comparing this
      partition with the soil properties measured with a shallow sampling, it was
      possible to verify the coherence in the topsoil between the dielectric properties
      and other properties more directly related to agronomic management. These results
      confirm the advantages of using proximal sensing as a preliminary step in the
      application of site-specific management. Combining disparate spatial data (data
      fusion) is not at all a naive problem and novel and powerful methods need to be
      developed.

PMID- 29207512
TI  - Molecular Investigation of the Stem Snap Point in Textile Hemp.
AB  - Fibre crops are important natural resources, as they sustainably provide bast
      fibres, an economically-valuable raw material used in the textile and
      biocomposite sectors. Among fibre crops, textile hemp (Cannabis sativa L.) is
      appreciated for its long and strong gelatinous bast fibres. The stem of fibre
      crops is a useful system for cell wall-oriented studies, because it shows a
      strong tissue polarity with a lignified inner core and a cellulosic hypolignified
      cortex, as well as a basipetal lignification gradient. Along the stem axis of
      fibre crops, a specific region, denoted snap point, marks the transition from
      elongation (above it) to fibre thickening (below it). After empirically
      determining the snap point by tilting the plant, we divided the stem segment
      containing it into three non-overlapping consecutive regions measuring 1 cm each,
      and carried out targeted RT-qPCR on cell wall-related genes separately, in outer
      and inner tissues. Different gene clusters can be observed, two of which are the
      major gene groups, i.e., one group with members expressed at higher levels in the
      inner tissues, and one group whose genes are more expressed in the cortex. The
      present results provide a molecular validation that the snap point is
      characterised by a gradient of events associated with the shift from fibre
      elongation to thickening.

PMID- 29207511
TI  - Subcellular Trafficking of the Papillomavirus Genome during Initial Infection:
      The Remarkable Abilities of Minor Capsid Protein L2.
AB  - Since 2012, our understanding of human papillomavirus (HPV) subcellular
      trafficking has undergone a drastic paradigm shift. Work from multiple
      laboratories has revealed that HPV has evolved a unique means to deliver its
      viral genome (vDNA) to the cell nucleus, relying on myriad host cell proteins and
      processes. The major breakthrough finding from these recent endeavors has been
      the realization of L2-dependent utilization of cellular sorting factors for the
      retrograde transport of vDNA away from degradative endo/lysosomal compartments to
      the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An
      overview of current models of HPV entry, subcellular trafficking, and the role of
      L2 during initial infection is provided below, highlighting unresolved questions
      and gaps in knowledge.

PMID- 29207513
TI  - Methylxanthine Content in Commonly Consumed Foods in Spain and Determination of
      Its Intake during Consumption.
AB  - Methylxanthines present psychostimulant effects. These compounds have low
      toxicity and their consumption at moderate levels presents some beneficial health
      effects, whereas some significant risk appears at high levels. Samples of common
      types of methylxanthine-containing beverages and foods consumed in Spain were
      analyzed to determine their content. Caffeine was the methylxanthine that was
      most found in the samples investigated. Instant coffees gave the highest caffeine
      percentage (18-44 mg.g-1). Green and scented teas were found to have a caffeine
      dry-weight content (8-26 mg.g-1) equivalent to ground coffees (13-23 mg.g-1), but
      black and pu-erh teas (18-30 mg.g-1) had a higher caffeine content. The
      evaluation of the most conventional methods for preparing espresso coffees showed
      that an espresso contains between 88-116 mg of caffeine. In the case of tea
      beverages, the amount of caffeine present was 2-3 times smaller than in espresso
      coffees. Energy drinks showed a similar caffeine content (80-106 mg) as espresso
      coffees. Chocolates had the lowest caffeine content. It has been found that none
      of the foods evaluated reach the recommended daily intake limit of 400 mg of
      caffeine with a single dose. This limit can be reached with 4-5 doses in the case
      of coffees and energy drinks. In the case of chocolates, the methylxanthine
      compound detected at large levels was theobromine, with amounts ranging from 4 to
      10 mg.g-1 for dark chocolates.

PMID- 29207514
TI  - Nutrition Counselling Practices among General Practitioners in Croatia.
AB  - Chronic non-communicable diseases are a significant public health problem and
      imbalanced nutrition is one of the most significant risk factor for them. The
      objective of this study was to examine Croatia's general practitioners' nutrition
      counselling practice and determine the factors that influence such practice. A
      cross-sectional study was conducted among 444 (17.0%) randomly selected general
      practitioners (GPs) in Croatia from May to July 2013 via a 32-item anonymous
      questionnaire. Study showed that 77.0% of participants had provided nutrition
      counselling exclusively to patients with specific health risks; 18.7%
      participants had provided nutrition counselling for all patients, regardless of
      their individual risks, while 4.3% had not provide nutrition counselling. As the
      most significant stimulating factor for implementing nutrition counselling in
      their daily work with patients, 55.6% of the participants identified personal
      interest regarding nutrition and the effects it has on health. The latter factor
      was more frequently emphasized among female general practitioners (p < 0.001) and
      general practitioners without chronic diseases (p < 0.001). The most significant
      barrier for nutrition counselling was lack of time (81.6%). It is necessary to
      make additional efforts to increase the frequency of nutrition counselling
      provided by general practitioners in Croatia. The majority of Croatian general
      practitioners could increase their nutrition counselling practice in order to
      promote balanced nutrition and improve the overall health status of their
      patients.

PMID- 29207515
TI  - A Low-Cost and Portable Dual-Channel Fiber Optic Surface Plasmon Resonance
      System.
AB  - A miniaturization and integration dual-channel fiber optic surface plasmon
      resonance (SPR) system was proposed and demonstrated in this paper. We used a
      yellow light-emitting diode (LED, peak wavelength 595 nm) and built-in web camera
      as a light source and detector, respectively. Except for the detection channel,
      one of the sensors was used as a reference channel to compensate nonspecific
      binding and physical absorption. We packaged the LED and surface plasmon
      resonance (SPR) sensors together, which are flexible enough to be applied to
      mobile devices as a compact and portable system. Experimental results show that
      the normalized intensity shift and refractive index (RI) of the sample have a
      good linear relationship in the RI range from 1.328 to 1.348. We used this sensor
      to monitor the reversible, specific interaction between lectin concanavalin A
      (Con A) and glycoprotein ribonuclease B (RNase B), which demonstrate its
      capabilities of specific identification and biochemical samples concentration
      detection. This sensor system has potential applications in various fields, such
      as medical diagnosis, public health, food safety, and environment monitoring.

PMID- 29207516
TI  - Equine Vaccines: How, When and Why? Report of the Vaccinology Session, French
      Equine Veterinarians Association, 2016, Reims.
AB  - To date, vaccination is one of the most efficient methods of prevention against
      equine infectious diseases. The vaccinology session, which was organised during
      the annual meeting of the French Equine Veterinarians Association (AVEF) at Reims
      (France) in 2016, aimed to approach three subjects of importance for the equine
      industry. Vaccination against three major equine diseases were used as examples:
      equine influenza (equine influenza virus), rhinopneumonitis (equine herpes virus
      1/4), and tetanus (Clostridium tetani neuro-toxin). (1) Emergency vaccination:
      while it has been very successful to reduce the impact of equine influenza
      epizooties and it is also recommended for tetanus in case of surgery and
      accident, the benefit of emergency vaccination against equine herpes virus 1/4
      remains arguable; (2) Compatibility of equine vaccines from different brands:
      despite being a frequent concerns for equine veterinarians, little information is
      available about the compatibility of equine vaccines from different commercial
      origins. The consequence of mixing different equine vaccines targeting the same
      disease is believed to be limited but scientific evidences are sparse; and, (3)
      Laps vaccination and vaccine shortage: they could have serious consequences in
      terms of protection and their impact should be evaluated on a case by case basis,
      taking into account the risk of contact with the pathogen and the effect on herd
      immunity.

PMID- 29207517
TI  - Monitoring the Activity of Immobilized Lipase with Quinizarin Diester Fluoro
      Chromogenic Probe.
AB  - Quinizarin diester is used as a fluoro-chromogenic substrate of the activity of
      lipase supported in poly(methylmetacrylate) beads (CALB, Novozym(r) 435)
      dispersed in organic solvents. The monoester and diester of quinizarin are both
      non-fluorescent species contrasting with the enzymatic product quinizarin that
      shows optical absorption in the visible region and strong fluorescence signal.
      The enzymatic conversion is accomplished by spectroscopic measurements and it
      follows a sigmoid curve from which the mean reaction time of the enzymatic
      process can be determined. This parameter indicates the enzyme activity of the
      immobilized lipase. Its dependency with the amount of lipase allowed the
      determination of the ratio of the catalytic rate and the Michaelis constant
      (kc/Km) and the experimental value found was (1.0 +/- 0.1) * 10-2 mg-1/min in the
      case of quinizarin diacetate.

PMID- 29207518
TI  - Highly Sensitive and Stretchable Strain Sensor Based on Ag@CNTs.
AB  - Due to the rapid development and superb performance of electronic skin, we
      propose a highly sensitive and stretchable temperature and strain sensor. Silver
      nanoparticles coated carbon nanowires (Ag@CNT) nanomaterials with different Ag
      concentrations were synthesized. After the morphology and components of the
      nanomaterials were demonstrated, the sensors composed of Polydimethylsiloxane
      (PDMS) and CNTs or Ag@CNTs were prepared via a simple template method. Then, the
      electronic properties and piezoresistive effects of the sensors were tested.
      Characterization results present excellent performance of the sensors for the
      highest gauge factor (GF) of the linear region between 0-17.3% of the sensor with
      Ag@CNTs1 was 137.6, the sensor with Ag@CNTs2 under the strain in the range of 0
      54.8% exhibiting a perfect linearity and the GF of the sensor with Ag@CNTs2 was
      14.9.

PMID- 29207519
TI  - A Diastereoselective Synthesis of Dispiro[oxindole-cyclohexanone]pyrrolidines by
      1,3-Dipolar Cycloaddition.
AB  - For the first time, arylmethylidene cyclohexanones that are non-symmetrical due
      to the presence of peripheral substituents were studied in 1,3-dipolar
      cycloaddition reactions. It is shown that the interaction with the azomethine
      ylide generated from sarcosine proceeds regio- and diastereoselectively, with the
      participation of two non-equivalent parts of the dipolarophile. Also for the
      first time, beta-amino ketones (Mannich bases) were used as dipolarophile
      equivalents of unsaturated ketones. It was found that cycloaddition occurs
      diastereoselectively at the generated center.

PMID- 29207521
TI  - "I Am Ready and Willing to Provide the Service ... Though My Religion Frowns on
      Abortion"-Ghanaian Midwives' Mixed Attitudes to Abortion Services: A Qualitative
      Study.
AB  - BACKGROUND: Unsafe abortion is a major preventable public health problem and
      contributes to high mortality among women. Ghana has ratified international
      conventions to prevent unwanted pregnancies and provide safe abortion services,
      legally authorizing midwives to provide induced abortion services in certain
      circumstances. OBJECTIVE: The aim of the study was to understand midwives'
      readiness to be involved in legal induced abortions, should the law become less
      restricted in Ghana. METHODS: A qualitative study design, with a topic guide for
      individual in-depth interviews of selected midwives, was adopted. The interviews
      were tape-recorded and analyzed using content analysis. RESULTS: Participants
      emphasized their willingness to reduce maternal mortalities, their experiences of
      maternal deaths, and their passion for the health of pregnant women. Knowledge of
      Ghana's abortion law was generally low. Different views were expressed regarding
      readiness to engage in abortion services. Some expressed it as being sinful and
      against their religion to assist in abortion care, whilst others felt it was good
      to save the lives of women. CONCLUSION: The midwives made it clear that unsafe
      abortions are common, stigmatizing and contributing to maternal mortality, issues
      that must be addressed. They made various suggestions to reduce this preventable
      tragedy.

PMID- 29207520
TI  - Plants of the Genus Zingiber as a Source of Bioactive Phytochemicals: From
      Tradition to Pharmacy.
AB  - Plants of the genus Zingiber (Family Zingiberaceae) are widely used throughout
      the world as food and medicinal plants. They represent very popular herbal
      remedies in various traditional healing systems; in particular, rhizome of
      Zingiber spp. plants has a long history of ethnobotanical uses because of a
      plethora of curative properties. Antimicrobial activity of rhizome essential oil
      has been extensively confirmed in vitro and attributed to its chemical
      components, mainly consisting of monoterpene and sesquiterpene hydrocarbons such
      as alpha-zingiberene, ar-curcumene, beta-bisabolene and beta-sesquiphellandrene.
      In addition, gingerols have been identified as the major active components in the
      fresh rhizome, whereas shogaols, dehydrated gingerol derivatives, are the
      predominant pungent constituents in dried rhizome. Zingiber spp. may thus
      represent a promising and innovative source of natural alternatives to chemical
      food preservatives. This approach would meet the increasing concern of consumers
      aware of the potential health risks associated with the conventional
      antimicrobial agents in food. This narrative review aims at providing a
      literature overview on Zingiber spp. plants, their cultivation, traditional uses,
      phytochemical constituents and biological activities.

PMID- 29207522
TI  - Using the SPE and Micro-HPLC-MS/MS Method for the Analysis of Betalains in Rat
      Plasma after Red Beet Administration.
AB  - The objective of this study was to develop a simple and reproducible method for
      the qualitative and quantitative analysis of betalains in plasma samples, based
      on Solid Phase Extraction (SPE) and micro-high performance liquid chromatography
      coupled with mass spectrometry (micro-HPLC-MS/MS). The eight betalain compounds
      detected and quantified were characterized in the fortified rat blood plasma
      samples. The developed method showed a good coefficient of determination (R2 =
      0.999), good recovery, precision, and appropriate limits of detection (LOD) and
      quantification (LOQ) for these compounds. Application of this method for the
      treatment of rat plasma samples collected after the betalain preparation
      administration, for the first time, revealed the presence of native betalains and
      their metabolites in plasma samples. Moreover, among them, betanin (2.14 +/- 0.06
      umol/L) and isobetanin (3.28 +/- 0.04 umol/L) were found at the highest
      concentration. The results indicated that the combination of an SPE method with a
      micro-HPLC-MS/MS analysis may be successfully applied for the determination of
      betalains in the blood plasma.

PMID- 29207523
TI  - 31iemes Journees Franco-Belges de Pharmacochimie: Meeting Report.
AB  - The "Journees Franco-Belges de Pharmacochimie" is a recognized two-day annual
      meeting on Medicinal Chemistry that is renowned for the advanced science
      presented, conviviality, and outstanding opportunities for senior and young
      scientists to exchange knowledge. Abstracts of plenary lectures, oral
      communications, and posters presented during the meeting are collected in this
      report.

PMID- 29207524
TI  - Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat
      (Eidolon helvum).
AB  - Bats are important reservoirs for emerging zoonotic viruses. For extensive
      surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in
      Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto
      Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106)
      exhibited remarkable cytopathic changes. Based on the ultrastructural property in
      negative staining and cross-reactivity in immunofluorescence assays, the virus
      was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06
      106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined
      by next-generation sequencing, showed the presence of 28 open reading frames.
      Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat
      adenovirus species in the genus Mastadenovirus. The virus shared similar
      characteristics of low G + C contents with recently isolated members of species
      Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than
      15% based on the distance matrix analysis of DNA polymerase amino acid sequences.
      According to the taxonomic criteria, we propose the tentative new species name
      "Bat mastadenovirus H". Because EhAdV 06-106 exhibited a wide in vitro cell
      tropism, the virus might have a potential risk as an emerging virus through cross
      species transmission.

PMID- 29207525
TI  - Phenylpropionamides, Piperidine, and Phenolic Derivatives from the Fruit of
      Ailanthus altissima.
AB  - Four novel compounds-two phenylpropionamides, one piperidine, and one phenolic
      derivatives-were isolated and identified from the fruit of a medicinal plant,
      Ailanthus altissima (Mill.) Swingle (Simaroubaceae), together with one known
      phenylpropionamide, 13 known phenols, and 10 flavonoids. The structures of the
      new compounds were elucidated as 2-hydroxy-N-[(2-O-beta-d
      glucopyranosyl)phenyl]propionamide (1), 2-hydroxy-N-[(2-O-beta-d-glucopyranosyl
      (1->6)-beta-d-glucopyranosyl)phenyl]propionamide (2), 2beta-carboxyl-piperidine
      4beta-acetic acid methyl ester (4), and 4-hydroxyphenyl-1-O-[6-(hydrogen-3
      hydroxy-3-methylpentanedioate)]-beta-d-glucopyranoside (5) based on spectroscopic
      analysis. All the isolated compounds were evaluated for their inhibitory activity
      against Tobacco mosaic virus (TMV) using the leaf-disc method. Among the
      compounds isolated, arbutin (6), beta-d-glucopyranosyl-(1->6)-arbutin (7), 4
      methoxyphenylacetic acid (10), and corilagin (18) showed moderate inhibition
      against TMV with IC50 values of 0.49, 0.51, 0.27, and 0.45 mM, respectively.

PMID- 29207526
TI  - Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical
      Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal
      Transition Associated Transcription Factors Twist1 and Zeb1.
AB  - Cervical cancer is one of the most common gynecological malignant tumors
      worldwide, for which chemotherapeutic strategies are limited due to their non
      specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ)
      has been reported to target a vast number of signaling pathways in carcinogenesis
      in different cancers, and hence is regarded as a promising anticancer molecule.
      Inhibition of epithelial to mesenchymal transition (EMT) regulators is an
      important approach in anticancer research. In this study, TQ was used to treat
      the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT
      regulatory proteins and cancer metastasis. Our results showed that TQ has time
      dependent and dose-dependent cytotoxic effects, and it also inhibits the
      migration and invasion processes in different cervical cancer cells. At the
      molecular level, TQ treatment inhibited the expression of Twist1, Zeb1
      expression, and increased E-Cadherin expression. Luciferase reporter assay showed
      that TQ decreases the Twist1 and Zeb1 promoter activities respectively,
      indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also
      increased cellular apoptosis in some extent, but apoptotic genes/proteins we
      tested were not significant affected. We conclude that TQ inhibits the migration
      and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and
      Zeb1/E-Cadherin/EMT, among other signaling pathways.

PMID- 29207527
TI  - Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells
      with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with
      Targeted Toxin-Based Selection System.
AB  - The recent advancement in genome editing such a CRISPR/Cas9 system has enabled
      isolation of cells with knocked multiple alleles through a one-step transfection.
      Somatic cell nuclear transfer (SCNT) has been frequently employed as one of the
      efficient tools for the production of genetically modified (GM) animals. To use
      GM cells as SCNT donor, efficient isolation of transfectants with mutations at
      multiple target loci is often required. The methods for the isolation of such GM
      cells largely rely on the use of drug selection-based approach using selectable
      genes; however, it is often difficult to isolate cells with mutations at multiple
      target loci. In this study, we used a novel approach for the efficient isolation
      of porcine cells with at least two target loci mutations by one-step introduction
      of CRISPR/Cas9-related components. A single guide (sg) RNA targeted to GGTA1
      gene, involved in the synthesis of cell-surface alpha-Gal epitope (known as
      xenogenic antigen), is always a prerequisite. When the transfected cells were
      reacted with toxin-labeled BS-I-B4 isolectin for 2 h at 37 C to eliminate alpha
      Gal epitope-expressing cells, the surviving clones lacked alpha-Gal epitope
      expression and were highly expected to exhibit induced mutations at another
      target loci. Analysis of these alpha-Gal epitope-negative surviving cells
      demonstrated a 100% occurrence of genome editing at target loci. SCNT using these
      cells as donors resulted in the production of cloned blastocysts with the
      genotype similar to that of the donor cells used. Thus, this novel system will be
      useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple
      target loci may be mutated.

PMID- 29207529
TI  - Improving the Catalytic Property of the Glycoside Hydrolase LXYL-P1-2 by Directed
      Evolution.
AB  - The glycoside hydrolase LXYL-P1-2 from Lentinula edodes can specifically
      hydrolyze 7-beta-xylosyltaxanes to form 7-beta-hydroxyltaxanes for the semi
      synthesis of paclitaxel. In order to improve the catalytic properties of the
      enzyme, we performed error-prone PCR to construct the random mutant library of
      LXYL-P1-2 and used the methanol-induced plate method to screen the mutants with
      improved catalytic properties. Two variants, LXYL-P1-2-EP1 (EP1, S91D mutation)
      and LXYL-P1-2-EP2 (EP2, T368E mutation), were obtained from the library and
      exhibited 17% and 47% increases in their catalytic efficiencies on 7-beta-xylosyl
      10-deacetyltaxol. Meanwhile, compared with LXYL-P1-2, EP1 and EP2 showed elevated
      stabilities in the range of pH >= 6 conditions. After treatment at pH 12 for 48
      h, EP1 and EP2 retained 77% and 63% activities, respectively, while the wild-type
      only retained 33% activity under the same condition. Molecular docking results
      revealed that the S91D mutation led to a shorter distance between the R-chain and
      the substrate, while the T368E mutation increased negative charge at the surface
      of the enzyme, and may introduce alterations of the loop near the active pocket,
      both of which may result in improved stabilities and catalytic activities of
      enzymes. This study provides a practical directed evolution method for exploring
      catalytically improved glycoside hydrolase.

PMID- 29207528
TI  - Construction and Potential Applications of Biosensors for Proteins in Clinical
      Laboratory Diagnosis.
AB  - Biosensors for proteins have shown attractive advantages compared to traditional
      techniques in clinical laboratory diagnosis. In virtue of modern fabrication
      modes and detection techniques, various immunosensing platforms have been
      reported on basis of the specific recognition between antigen-antibody pairs. In
      addition to profit from the development of nanotechnology and molecular biology,
      diverse fabrication and signal amplification strategies have been designed for
      detection of protein antigens, which has led to great achievements in fast
      quantitative and simultaneous testing with extremely high sensitivity and
      specificity. Besides antigens, determination of antibodies also possesses great
      significance for clinical laboratory diagnosis. In this review, we will
      categorize recent immunosensors for proteins by different detection techniques.
      The basic conception of detection techniques, sensing mechanisms, and the
      relevant signal amplification strategies are introduced. Since antibodies and
      antigens have an equal position to each other in immunosensing, all biosensing
      strategies for antigens can be extended to antibodies under appropriate
      optimizations. Biosensors for antibodies are summarized, focusing on potential
      applications in clinical laboratory diagnosis, such as a series of biomarkers for
      infectious diseases and autoimmune diseases, and an evaluation of vaccine
      immunity. The excellent performances of these biosensors provide a prospective
      space for future antibody-detection-based disease serodiagnosis.

PMID- 29207530
TI  - Characterization of Ultrasound Energy Diffusion Due to Small-Size Damage on an
      Aluminum Plate Using Piezoceramic Transducers.
AB  - During the propagation of ultrasonic waves in structures, there is usually energy
      loss due to ultrasound energy diffusion and dissipation. The aim of this research
      is to characterize the ultrasound energy diffusion that occurs due to small-size
      damage on an aluminum plate using piezoceramic transducers, for the future
      purpose of developing a damage detection algorithm. The ultrasonic energy
      diffusion coefficient is related to the damage distributed in the medium.
      Meanwhile, the ultrasonic energy dissipation coefficient is related to the
      inhomogeneity of the medium. Both are usually employed to describe the
      characteristics of ultrasound energy diffusion. The existence of multimodes of
      Lamb waves in metallic plate structures results in the asynchronous energy
      transport of different modes. The mode of Lamb waves has a great influence on
      ultrasound energy diffusion as a result, and thus has to be chosen appropriately.
      In order to study the characteristics of ultrasound energy diffusion in metallic
      plate structures, an experimental setup of an aluminum plate with a through-hole,
      whose diameter varies from 0.6 mm to 1.2 mm, is used as the test specimen with
      the help of piezoceramic transducers. The experimental results of two categories
      of damages at different locations reveal that the existence of damage changes the
      energy transport between the actuator and the sensor. Also, when there is only
      one dominate mode of Lamb wave excited in the structure, the ultrasound energy
      diffusion coefficient decreases approximately linearly with the diameter of the
      simulated damage. Meanwhile, the ultrasonic energy dissipation coefficient
      increases approximately linearly with the diameter of the simulated damage.
      However, when two or more modes of Lamb waves are excited, due to the existence
      of different group velocities between the different modes, the energy transport
      of the different modes is asynchronous, and the ultrasonic energy diffusion is
      not strictly linear with the size of the damage. Therefore, it is recommended
      that only one dominant mode of Lamb wave should be excited during the
      characterization process, in order to ensure that the linear relationship between
      the damage size and the characteristic parameters is maintained. In addition, the
      findings from this paper demonstrate the potential of developing future damage
      detection algorithms using the linear relationships between damage size and the
      ultrasound energy diffusion coefficient or ultrasonic energy dissipation
      coefficient when a single dominant mode is excited.

PMID- 29207532
TI  - Relationship among Phosphorus Circulation Activity, Bacterial Biomass, pH, and
      Mineral Concentration in Agricultural Soil.
AB  - Improvement of phosphorus circulation in the soil is necessary to enhance
      phosphorus availability to plants. Phosphorus circulation activity is an index of
      soil's ability to supply soluble phosphorus from organic phosphorus in the soil
      solution. To understand the relationship among phosphorus circulation activity;
      bacterial biomass; pH; and Fe, Al, and Ca concentrations (described as mineral
      concentration in this paper) in agricultural soil, 232 soil samples from various
      agricultural fields were collected and analyzed. A weak relationship between
      phosphorus circulation activity and bacterial biomass was observed in all soil
      samples (R2 = 0.25), and this relationship became significantly stronger at near
      neutral pH (6.0-7.3; R2 = 0.67). No relationship between phosphorus circulation
      activity and bacterial biomass was observed at acidic (pH < 6.0) or alkaline (pH
      > 7.3) pH. A negative correlation between Fe and Al concentrations and phosphorus
      circulation activity was observed at acidic pH (R2 = 0.72 and 0.73,
      respectively), as well as for Ca at alkaline pH (R2 = 0.64). Therefore, bacterial
      biomass, pH, and mineral concentration should be considered together for
      activation of phosphorus circulation activity in the soil. A relationship model
      was proposed based on the effects of bacterial biomass and mineral concentration
      on phosphorus circulation activity. The suitable conditions of bacterial biomass,
      pH, and mineral concentration for phosphorus circulation activity could be
      estimated from the relationship model.

PMID- 29207531
TI  - Microbial and Plant-Assisted Bioremediation of Heavy Metal Polluted Environments:
      A Review.
AB  - Environmental pollution from hazardous waste materials, organic pollutants and
      heavy metals, has adversely affected the natural ecosystem to the detriment of
      man. These pollutants arise from anthropogenic sources as well as natural
      disasters such as hurricanes and volcanic eruptions. Toxic metals could
      accumulate in agricultural soils and get into the food chain, thereby becoming a
      major threat to food security. Conventional and physical methods are expensive
      and not effective in areas with low metal toxicity. Bioremediation is therefore
      an eco-friendly and efficient method of reclaiming environments contaminated with
      heavy metals by making use of the inherent biological mechanisms of
      microorganisms and plants to eradicate hazardous contaminants. This review
      discusses the toxic effects of heavy metal pollution and the mechanisms used by
      microbes and plants for environmental remediation. It also emphasized the
      importance of modern biotechnological techniques and approaches in improving the
      ability of microbial enzymes to effectively degrade heavy metals at a faster
      rate, highlighting recent advances in microbial bioremediation and
      phytoremediation for the removal of heavy metals from the environment as well as
      future prospects and limitations. However, strict adherence to biosafety
      regulations must be followed in the use of biotechnological methods to ensure
      safety of the environment.

PMID- 29207534
TI  - Effects of the Macular Carotenoid Lutein in Human Retinal Pigment Epithelial
      Cells.
AB  - Retinal pigment epithelial (RPE) cells are central to retinal health and
      homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the
      pathogenesis of age-related macular degeneration and neovascular retinopathies
      (e.g., retinopathy of prematurity, diabetic retinopathy). The xanthophyll
      carotenoids, lutein and zeaxanthin, are selectively taken up by the RPE,
      preferentially accumulated in the human macula, and transferred to
      photoreceptors. These macular xanthophylls protect the macula (and the broader
      retina) via their antioxidant and photo-protective activities. This study was
      designed to investigate effects of various carotenoids (beta-carotene, lycopene,
      and lutein) on RPE cells subjected to either hypoxia or oxidative stress, in
      order to determine if there is effect specificity for macular pigment
      carotenoids. Using human RPE-derived ARPE-19 cells as an in vitro model, we
      exposed RPE cells to various concentrations of the specific carotenoids, followed
      by either graded hypoxia or oxidative stress using tert-butyl hydroperoxide
      (tBHP). The results indicate that lutein and lycopene, but not beta-carotene,
      inhibit cell growth in undifferentiated ARPE-19 cells. Moreover, cell viability
      was decreased under hypoxic conditions. Pre-incubation of ARPE-19 cells with
      lutein or lycopene protected against tBHP-induced cell loss and cell co-exposure
      of lutein or lycopene with tBHP essentially neutralized tBHP-dependent cell death
      at tBHP concentrations up to 500 MUM. Our findings indicate that lutein and
      lycopene inhibit the growth of human RPE cells and protect the RPE against
      oxidative stress-induced cell loss. These findings contribute to the
      understanding of the protective mechanisms attributable to retinal xanthophylls
      in eye health and retinopathies.

PMID- 29207535
TI  - Contamination Event Detection with Multivariate Time-Series Data in Agricultural
      Water Monitoring.
AB  - Time series data of multiple water quality parameters are obtained from the water
      sensor networks deployed in the agricultural water supply network. The accurate
      and efficient detection and warning of contamination events to prevent pollution
      from spreading is one of the most important issues when pollution occurs. In
      order to comprehensively reduce the event detection deviation, a spatial-temporal
      based event detection approach with multivariate time-series data for water
      quality monitoring (M-STED) was proposed. The M-STED approach includes three
      parts. The first part is that M-STED adopts a Rule K algorithm to select backbone
      nodes as the nodes in the CDS, and forward the sensed data of multiple water
      parameters. The second part is to determine the state of each backbone node with
      back propagation neural network models and the sequential Bayesian analysis in
      the current timestamp. The third part is to establish a spatial model with
      Bayesian networks to estimate the state of the backbones in the next timestamp
      and trace the "outlier" node to its neighborhoods to detect a contamination
      event. The experimental results indicate that the average detection rate is more
      than 80% with M-STED and the false detection rate is lower than 9%, respectively.
      The M-STED approach can improve the rate of detection by about 40% and reduce the
      false alarm rate by about 45%, compared with the event detection with a single
      water parameter algorithm, S-STED. Moreover, the proposed M-STED can exhibit
      better performance in terms of detection delay and scalability.

PMID- 29207533
TI  - Molecular and Genetic Determinants of Glioma Cell Invasion.
AB  - A diffusely invasive nature is a major obstacle in treating a malignant brain
      tumor, "diffuse glioma", which prevents neurooncologists from surgically removing
      the tumor cells even in combination with chemotherapy and radiation. Recently
      updated classification of diffuse gliomas based on distinct genetic and
      epigenetic features has culminated in a multilayered diagnostic approach to
      combine histologic phenotypes and molecular genotypes in an integrated diagnosis.
      However, it is still a work in progress to decipher how the genetic aberrations
      contribute to the aggressive nature of gliomas including their highly invasive
      capacity. Here we depict a set of recent discoveries involving molecular genetic
      determinants of the infiltrating nature of glioma cells, especially focusing on
      genetic mutations in receptor tyrosine kinase pathways and metabolic
      reprogramming downstream of common cancer mutations. The specific biology of
      glioma cell invasion provides an opportunity to explore the genotype-phenotype
      correlation in cancer and develop novel glioma-specific therapeutic strategies
      for this devastating disease.

PMID- 29207536
TI  - Text Messaging Based Obesity Prevention Program for Parents of Pre-Adolescent
      African American Girls.
AB  - African American girls are at a greater risk of obesity than their nonminority
      peers. Parents have the primary control over the home environment and play an
      important role in the child obesity prevention. Obesity prevention programs to
      help parents develop an obesity-preventive home environment are needed. The
      purpose of this study was to collect formative research from parents of 8-10-year
      old African American girls about perceptions, expectations, and content for a
      text messaging based program. Mothers (n = 30) participated in surveys and
      interviews to inform message development and content. A professional expert panel
      (n = 10) reviewed draft text messages via a survey. All the mothers reported
      owning a cellphone with an unlimited texting plan, and they used their cellphones
      for texting (90.0%) and accessing the Internet (100.0%). The majority were
      interested in receiving text messages about healthy eating and physical activity
      (86.7%). Interviews confirmed survey findings. One hundred and seven text
      messages promoting an obesity-preventive home environment were developed. The
      expert panel and parents reported positive reactions to draft text messages. This
      research provides evidence that mobile health (mHealth) interventions appeal to
      parents of African American girls and they have ready access to the technology
      with which to support this approach.

PMID- 29207537
TI  - A Robust Indoor/Outdoor Navigation Filter Fusing Data from Vision and Magneto
      Inertial Measurement Unit.
AB  - Visual-inertial Navigation Systems (VINS) are nowadays used for robotic or
      augmented reality applications. They aim to compute the motion of the robot or
      the pedestrian in an environment that is unknown and does not have specific
      localization infrastructure. Because of the low quality of inertial sensors that
      can be used reasonably for these two applications, state of the art VINS rely
      heavily on the visual information to correct at high frequency the drift of
      inertial sensors integration. These methods struggle when environment does not
      provide usable visual features, such than in low-light of texture-less areas. In
      the last few years, some work have been focused on using an array of
      magnetometers to exploit opportunistic stationary magnetic disturbances available
      indoor in order to deduce a velocity. This led to Magneto-inertial Dead-reckoning
      (MI-DR) systems that show interesting performance in their nominal conditions,
      even if they can be defeated when the local magnetic gradient is too low, for
      example outdoor. We propose in this work to fuse the information from a monocular
      camera with the MI-DR technique to increase the robustness of both traditional
      VINS and MI-DR itself. We use an inverse square root filter inspired by the MSCKF
      algorithm and describe its structure thoroughly in this paper. We show navigation
      results on a real dataset captured by a sensor fusing a commercial-grade camera
      with our custom MIMU (Magneto-inertial Measurment Unit) sensor. The fused
      estimate demonstrates higher robustness compared to pure VINS estimate, specially
      in areas where vision is non informative. These results could ultimately increase
      the working domain of mobile augmented reality systems.

PMID- 29207538
TI  - Bioinspiring Chondrosia reniformis (Nardo, 1847) Collagen-Based Hydrogel: A New
      Extraction Method to Obtain a Sticky and Self-Healing Collagenous Material.
AB  - Collagen is a natural and abundant polymer that serves multiple functions in both
      invertebrates and vertebrates. As collagen is the natural scaffolding for cells,
      collagen-based hydrogels are regarded as ideal materials for tissue engineering
      applications since they can mimic the natural cellular microenvironment.
      Chondrosia reniformis is a marine demosponge particularly rich in collagen,
      characterized by the presence of labile interfibrillar crosslinks similarly to
      those described in the mutable collagenous tissues (MCTs) of echinoderms. As a
      result single fibrils can be isolated using calcium-chelating and disulphide
      reducing chemicals. In the present work we firstly describe a new extraction
      method that directly produces a highly hydrated hydrogel with interesting self
      healing properties. The materials obtained were then biochemically and
      rheologically characterized. Our investigation has shown that the developed
      extraction procedure is able to extract collagen as well as other proteins and
      Glycosaminoglycans (GAG)-like molecules that give the collagenous hydrogel
      interesting and new rheological properties when compared to other described
      collagenous materials. The present work motivates further in-depth investigations
      towards the development of a new class of injectable collagenous hydrogels with
      tailored specifications.

PMID- 29207539
TI  - Comprehensive Profiling and Quantification of Ginsenosides in the Root, Stem,
      Leaf, and Berry of Panax ginseng by UPLC-QTOF/MS.
AB  - The effective production and usage of ginsenosides, given their distinct
      pharmacological effects, are receiving increasing amounts of attention. As the
      ginsenosides content differs in different parts of Panax ginseng, we wanted to
      assess and compare the ginsenosides content in the ginseng roots, leave, stems,
      and berries. To extract the ginsenosides, 70% (v/v) methanol was used. The
      optimal ultra-performance liquid chromatography-quadrupole time of flight mass
      spectrometry (UPLC-QTOF/MS) method was used to profile various ginsenosides from
      the different parts of P. ginseng. The datasets were then subjected to
      multivariate analysis including principal component analysis (PCA) and
      hierarchical clustering analysis (HCA). A UPLC-QTOF/MS method with an in-house
      library was constructed to profile 58 ginsenosides. With this method, a total of
      39 ginsenosides were successfully identified and quantified in the ginseng roots,
      leave, stem, and berries. PCA and HCA characterized the different ginsenosides
      compositions from the different parts. The quantitative ginsenoside contents were
      also characterized from each plant part. The results of this study indicate that
      the UPLC-QTOF/MS method can be an effective tool to characterize various
      ginsenosides from the different parts of P. ginseng.

PMID- 29207541
TI  - Node Depth Adjustment Based Target Tracking in UWSNs Using Improved Harmony
      Search.
AB  - Underwater wireless sensor networks (UWSNs) can provide a promising solution to
      underwater target tracking. Due to the limited computation and bandwidth
      resources, only a small part of nodes are selected to track the target at each
      interval. How to improve tracking accuracy with a small number of nodes is a key
      problem. In recent years, a node depth adjustment system has been developed and
      applied to issues of network deployment and routing protocol. As far as we know,
      all existing tracking schemes keep underwater nodes static or moving with water
      flow, and node depth adjustment has not been utilized for underwater target
      tracking yet. This paper studies node depth adjustment method for target tracking
      in UWSNs. Firstly, since a Fisher Information Matrix (FIM) can quantify the
      estimation accuracy, its relation to node depth is derived as a metric. Secondly,
      we formulate the node depth adjustment as an optimization problem to determine
      moving depth of activated node, under the constraint of moving range, the value
      of FIM is used as objective function, which is aimed to be minimized over moving
      distance of nodes. Thirdly, to efficiently solve the optimization problem, an
      improved Harmony Search (HS) algorithm is proposed, in which the generating
      probability is modified to improve searching speed and accuracy. Finally,
      simulation results are presented to verify performance of our scheme.

PMID- 29207540
TI  - Herpesvirus and Autophagy: "All Right, Everybody Be Cool, This Is a Robbery!"
AB  - Autophagy is an essential vacuolar process of the cell, leading to lysosomal
      degradation and recycling of proteins and organelles, which is extremely
      important in maintaining homeostasis. Multiple roles have been now associated
      with autophagy, in particular a pro-survival role in nutrient starvation or in
      stressful environments, a role in life span extension, in development, or in
      innate and adaptive immunity. This cellular process can also take over
      microorganisms or viral proteins inside autophagosomes and degrade them directly
      in autolysosomes and is then called xenophagy and virophagy, respectively.
      Several Herpesviruses have developed strategies to escape this degradation, by
      expression of specific anti-autophagic proteins. However, we are increasingly
      discovering that Herpesviruses hijack autophagy, rather than just fight it. This
      beneficial effect is obvious since inhibition of autophagy will lead to decreased
      viral titers for human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) or
      Varicella-Zoster virus (VZV), for example. Conversely, autophagy stimulation will
      improve viral multiplication. The autophagic machinery can be used in whole or in
      part, and can optimize viral propagation or persistence. Some viruses block
      maturation of autophagosomes to avoid the degradation step, then autophagosomal
      membranes are used to contribute to the envelopment and/or the egress of viral
      particles. On the other hand, VZV stimulates the whole process of autophagy to
      subvert it in order to use vesicles containing ATG (autophagy-related) proteins
      and resembling amphisomes for their transport in the cytoplasm. During latency,
      autophagy can also be activated by latent proteins encoded by different oncogenic
      Herpesviruses to promote cell survival and achieve long term viral persistence in
      vivo. Finally, reactivation of gammaherpesvirus Murid Herpesvirus 68 (MHV68) in
      mice appears to be positively modulated by autophagy, in order to control the
      level of inflammation. Therefore, Herpesviruses appear to behave more like
      thieves than fugitives.

PMID- 29207542
TI  - Mapping Sensory Spots for Moderate Temperatures on the Back of Hand.
AB  - Thermosensation with thermoreceptors plays an important role in maintaining body
      temperature at an optimal state and avoiding potential damage caused by harmful
      hot or cold environmental temperatures. In this work, the locations of sensory
      spots for sensing moderate temperatures of 40-50  degrees C on the back of the
      hands of young Chinese people were mapped in a blind-test manner with a thermal
      probe of 1.0 mm spatial resolution. The number of sensory spots increased along
      with the testing temperature; however, the surface density of sensory spots was
      remarkably lower than those reported previously. The locations of the spots were
      irregularly distributed and subject-dependent. Even for the same subject, the
      number and location of sensory spots were unbalanced and asymmetric between the
      left and right hands. The results may offer valuable information for designing
      artificial electronic skin and wearable devices, as well as for clinical
      applications.

PMID- 29207543
TI  - The Effects of Carbon Nanotubes on the Mechanical and Wear Properties of AZ31
      Alloy.
AB  - Carbon nanotube (CNT)-reinforced AZ31 matrix nanocomposites were successfully
      fabricated using a powder metallurgy method followed by hot extrusion. The
      influence of CNTs on microstructures, mechanical properties, and wear properties
      were systematically investigated by optical microscope (OM), scanning electron
      microscope (SEM), X-ray diffraction (XRD), hardness test, tensile test, and wear
      test. The results revealed that the nanocomposites showed a slightly smaller
      grain size compared with the matrix and uniform distribution that CNTs could
      achieve at proper content. As a result, the addition of CNTs could weaken basal
      plane texture. However, the yield strength and ultimate tensile strength of the
      composites were enhanced as the amount of CNTs increased up to 2.0 wt. %,
      reaching maximum values of 241 MPa (+28.2%) and 297 MPa (+6.1%), respectively.
      The load transfer mechanism, Orowan mechanism, and thermal mismatch mechanism
      played important roles in the enhancement of the yield strength, and several
      classical models were employed to predict the theoretical values. The effect of
      CNT content on the friction coefficient and weight loss of the nanocomposites was
      also studied. The relationships between the amount of CNTs, the friction
      coefficient, and weight loss could be described by the exponential decay model
      and the Boltzmann model, respectively.

PMID- 29207544
TI  - How Does Health-Related Advertising with a Regulatory Focus and Goal Framing
      Affect Attitudes toward Ads and Healthy Behavior Intentions?
AB  - The health costs of colorectal cancer have increased over the years in Taiwan.
      The National Health Insurance Administration (NHI) and the Health Promotion
      Administration of the Ministry of Health and Welfare (MOHW) in Taiwan advocate
      that people have to change their unhealthy behaviors; however, the number of
      patients of colorectal cancer is increasing annually. This research discussed the
      effects of healthy diet advocacy advertisements (ads) on healthy diet behavior
      intentions as influenced by the interactions between regulatory focus theory
      (RFT) and message framing effects. Both regulatory focus theory and message
      framing effect were discussed for the relationship between advertisement and
      behavior change in many fields, such as health-related behavior, pro
      environmental behavior, consumer choice, etc. We executed an experiment with four
      different types of public health advocacy ads. A 2 (regulatory focus: promotion
      vs. prevention) * 2 (message framing: gain framing vs. loss framing) two-factor
      experiment was adopted, and 201 valid participants responded to the
      questionnaire. Results indicated that if the ad's regulatory focus is promotion
      focus, viewers' attitudes toward the ad and their behavior intentions are more
      positive when the slogan of the ad is gain framing rather than loss framing via
      the multiple analysis of variance (MANOVA), and vice versa. Respondents found the
      communication easier to comprehend when the ads evoked the respondents'
      regulatory focus and applied the appropriate message framing, thus improving the
      efficacy of health-related advertising. We offer suggestions regarding the future
      use of health-related advertising for the MOHW.

PMID- 29207546
TI  - Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose
      Lock (MTLL) for GPS Receivers.
AB  - Frequency-locked detector (FLD) has been widely utilized in tracking loops of
      Global Positioning System (GPS) receivers to indicate their locking status. The
      relation between FLD and lock status has been seldom discussed. The traditional
      PLL experience is not suitable for FLL. In this paper, the threshold setting
      criteria for frequency-locked detector in the GPS receiver has been proposed by
      analyzing statistical characteristic of FLD output. The approximate probability
      distribution of frequency-locked detector is theoretically derived by using a
      statistical approach, which reveals the relationship between probabilities of
      frequency-locked detector and the carrier-to-noise ratio (C/N0) of the received
      GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection
      threshold and lock probability related to C/N0 can be further discovered by
      utilizing this probability. Therefore, a theoretical basis for threshold setting
      criteria in frequency locked loops for GPS receivers is provided based on mean
      time-to-lose-lock analysis.

PMID- 29207545
TI  - Plasma Sphingolipids in Acute Pancreatitis.
AB  - Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with
      systemic inflammatory response syndrome and, in the case of severe AP, a
      mortality rate ranging from 36% to 50%. Standard clinical treatment of AP
      includes intensive hydration, analgesia, and management of complications.
      Unfortunately, the direct treatment of AP at the level of its molecular
      pathomechanism has not yet been established. Recent studies indicate that the
      sphingolipid signaling pathway may be one of the important factors contributing
      to the development of inflammation in pancreatic diseases. In the current study,
      we sought to investigate this promising route. We examined the plasma
      sphingolipid profile of 44 patients with acute pancreatitis, dividing them into
      three groups: mild, moderate and severe AP. Samples were collected from these
      groups at days 1, 3 and 7 following their hospital admission. We demonstrated
      significant changes in blood plasma sphingolipids in relation to the time course
      of AP. We also found an inhibition of de novo ceramide synthesis in mild and
      moderate AP. However, the most important and novel finding was a significant
      elevation in sphingosine-1-phosphate (S1P) (a downstream metabolite of ceramide)
      in mild AP, as well as a dramatic reduction in the lipid molecule content in the
      early stage (days 1 and 3) of severe AP. This strongly indicates that plasma S1P
      could serve as a prognostic marker of AP severity.

PMID- 29207547
TI  - Predicted Release and Analysis of Novel ACE-I, Renin, and DPP-IV Inhibitory
      Peptides from Common Oat (Avena sativa) Protein Hydrolysates Using in Silico
      Analysis.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays an important role in
      regulating hypertension by controlling vasoconstriction and intravascular fluid
      volume. RAAS itself is largely regulated by the actions of renin (EC 3.4.23.15)
      and the angiotensin-I-converting enzyme (ACE-I; EC 3.4.15.1). The enzyme
      dipeptidyl peptidase-IV (DPP-IV; EC 3.4.14.5) also plays a role in the
      development of type-2 diabetes. The inhibition of the renin, ACE-I, and DPP-IV
      enzymes has therefore become a key therapeutic target for the treatment of
      hypertension and diabetes. The aim of this study was to assess the bioactivity of
      different oat (Avena sativa) protein isolates and their ability to inhibit the
      renin, ACE-I, and DPP-IV enzymes. In silico analysis was carried out to
      predictthe likelihood of bioactive inhibitory peptides occurring from oat protein
      hydrolysates following in silico hydrolysis with the proteases papain and ficin.
      Nine peptides, including FFG, IFFFL, PFL, WWK, WCY, FPIL, CPA, FLLA, and FEPL
      were subsequently chemically synthesised, and their bioactivities were confirmed
      using in vitro bioassays. The isolated oat proteins derived from seven different
      oat varieties were found to inhibit the ACE-I enzyme by between 86.5 +/- 10.7%
      and 96.5 +/- 25.8%, renin by between 40.5 +/- 21.5% and 70.9 +/- 7.6%, and DPP-IV
      by between 3.7 +/- 3.9% and 46.2 +/- 28.8%. The activity of the synthesised
      peptides was also determined.

PMID- 29207549
TI  - 9-Vinylanthracene Based Fluorogens: Synthesis, Structure-Property Relationships
      and Applications.
AB  - Fluorescent dyes with aggregation-induced emission (AIE) properties exhibit
      intensified emission upon aggregation. They are promising candidates to study
      biomolecules and cellular changes in aqueous environments when aggregation
      formation occurs. Here, we report a group of 9-position functionalized anthracene
      derivatives that were conveniently synthesized by the palladium-catalyzed Heck
      reaction. Using fluorometric analyses, these dyes were confirmed to show AIE
      behavior upon forming aggregates at high concentrations, in viscous solvents, and
      when poorly solubilized. Their photophysical properties were then further
      correlated with their structural features, using density functional theory (DFT)
      calculation. Finally, we demonstrated their potential applications in monitoring
      pH changes, quantifying globular proteins, as well as cell imaging with confocal
      microscopy.

PMID- 29207548
TI  - The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic
      Review on Early Psychosis, Autism, and ADHD.
AB  - In this systematic review, we will consider and debate studies that have explored
      the effects of omega-3 polyunsaturated fatty acids (PUFAs) in three major, and
      somehow related, developmental psychiatric disorders: Autism, Attention Deficit
      and Hyperactivity disorder and Psychosis. The impact of omega-3 PUFAs on clinical
      symptoms and, if possible, brain trajectory in children and adolescents suffering
      from these illnesses will be reviewed and discussed, considering the biological
      plausibility of the effects of omega-3 fatty acids, together with their potential
      perspectives in the field. Heterogeneity in study designs will be discussed in
      the light of differences in results and interpretation of studies carried out so
      far.

PMID- 29207550
TI  - Using Free Adoptions to Reduce Crowding and Euthanasia at Cat Shelters: An
      Australian Case Study.
AB  - Many healthy adult cats are euthanised annually in shelters, and novel approaches
      are required to reduce euthanasia rates. Waiving adoption fees is one such
      approach. However, concerns that less responsible owners will be attracted to
      free events persist among welfare groups. We evaluated evidence for differences
      in cat fate, health, and adherence to husbandry legislation via a case-study of a
      free adoption-drive for cats >=1 year at a Western Australian shelter. Post
      adoption outcomes were compared between free adopters and a control group of
      normal-fee adopters. The free adoption-drive rehomed 137 cats, increasing average
      weekly adoptions by 533%. First-time adopters were a significantly larger portion
      of the free cohort, as a result of mixed-media promotions. Both adopter groups
      selected cats of similar age; sex and pelage. Post-adoption, both groups retained
      >90% cats, reporting near identical incidences of medical and behavioural
      problems. Adopters did not differ in legislative compliance regarding fitting
      collars, registering cats, or allowing cats to roam. The shelter reported
      satisfaction with the adoption-drive, because in addition to relieving crowding
      of healthy adults, adoption of full-fee kittens increased 381%. Overall, we found
      no evidence for adverse outcomes associated with free adoptions. Shelters should
      not be dissuaded from occasional free adoption-drives during overflow periods.

PMID- 29207551
TI  - Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of
      Lipophilic Agents: Towards Transdermal Drug Administration in Neurological
      Disorders.
AB  - We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA)
      based nanohydrogels for effective transdermal delivery. First, hyaluronan
      conjugated dodecylamine (HA-Do) HA-based polymers to load the lipophilic agents
      were synthesized with hyaluronan (HA) and dodecylamine (Do) by varying the
      substitution ratio of Do to HA. The synthetic yield of HA-Do was more than 80%
      (HA-Do (A): 82.7 +/- 4.7%, HA-Do (B): 87.1 +/- 3.9% and HA-Do (C): 81.4 +/-
      4.5%). Subsequently, nanohydrogels were fabricated using the nanoemulsion method.
      Indocyanine green (ICG) simultaneously self-assembled with HA-Do, and the size
      depended on the substitution ratio of Do in HA-Do (nanohydrogel (A): 118.0 +/-
      2.2 nm, nanohydrogel (B): 121.9 +/- 11.4 nm, and nanohydrogel (C): 142.2 +/- 3.8
      nm). The nanohydrogels were delivered into cells, and had excellent
      biocompatibility. Especially, nanohydrogel (A) could deliver and permeate ICG
      into the deep skin layer, the dermis. This suggests that nanohydrogels can be
      potent transdermal delivery systems.

PMID- 29207552
TI  - Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for
      Magnetic Hyperthermia Cancer Treatment.
AB  - Targeting cancer cells without injuring normal cells is the prime objective in
      treatment of cancer. In this present study, solvothermal and wet chemical
      precipitation techniques were employed to synthesize iron oxide (IO),
      hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles
      for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed
      spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X
      ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field
      emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray
      spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles
      was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized
      nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and
      40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic
      field at room temperature (300 K). The magnetic hyperthermia study that was
      performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR
      value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia
      temperature (~45  degrees C) was reached within 3 min, which shows a very high
      efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells
      within 30 min exposure. These results could potentially open new perceptions for
      biomaterials that are aimed for anti-cancer therapies based on magnetic
      hyperthermia.

PMID- 29207553
TI  - Determination of the Relative Efficacy of Eicosapentaenoic Acid and
      Docosahexaenoic Acid for Anti-Cancer Effects in Human Breast Cancer Models.
AB  - Epidemiological studies have associated high fish oil consumption with decreased
      risk of breast cancer (BC). n-3 long chain polyunsaturated fatty acids (n-3
      LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish
      and fish oils exert anti-cancer effects. However, few studies have examined the
      relative efficacy of EPA and DHA alone and in mixtures on BC subtypes. This was
      the objective of the present review, as this research is a necessity for the
      translation of findings to human health and disease. The literature suggests that
      DHA has a greater anti-cancer effect in triple negative BC (TNBC). In estrogen
      positive (ER+) BC, DHA has a greater effect on cell viability, while both fatty
      acids have similar effects on apoptosis and proliferation. These effects are
      associated with preferential uptake of DHA into TNBC lipid rafts and EPA in ER+
      BC. EPA:DHA mixtures have anti-cancer activity; however, the ratio of EPA:DHA
      does not predict the relative incorporation of these two fatty acids into
      membrane lipids as EPA appears to be preferentially incorporated. In summary, DHA
      and EPA should be considered separately in the context of BC prevention. The
      elucidation of optimal EPA:DHA ratios will be important for designing targeted n
      3 LCPUFA treatments.

PMID- 29207554
TI  - The Synergetic Effect of Cash Transfers for Families, Child Sensitive Social
      Protection Programs, and Capacity Building for Effective Social Protection on
      Children's Nutritional Status in Nepal.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of the
      synergetic effect of child sensitive social protection programs, augmented by a
      capacity building for social protection and embedded within existing government's
      targeted resource transfers for families on child nutritional status. DESIGN: A
      repeat cross-sectional quasi-experimental design with measures taken pre-
      (October-December 2009) and post- (December 2014-February 2015) intervention in
      the intervention and comparison district. The comparison district received
      standard social welfare services in the form of targeted resource transfers
      (TRTs) for eligible families. The intervention district received the TRTs plus a
      child cash payment, augmented by a capacity building for effective social
      protection outcomes. Propensity scores were used in difference-in-differences
      models to compare the changes over time between the intervention and control
      groups. RESULTS: Propensity score matched/weighted models produced better results
      than the unmatched analyses, and hence we report findings from the radius
      matching. The intervention resulted in a 5.16 (95% CI: 9.55, 0.77), 7.35 (95% CI:
      11.62, 3.08) and 2.84 (95% CI: 5.58, 0.10) percentage point reduction in the
      prevalence of stunting, underweight, and wasting among children under the age,
      respectively. The intervention impact was greater in boys than girls for stunting
      and wasting; and greater in girls than boys for underweight. The intervention
      also resulted in a 6.66 (95% CI: 2.13, 3.18), 11.40 (95% CI: 16.66, 6.13), and
      4.0 (95% CI: 6.43, 1.78) percentage point reduction in the prevalence of
      stunting, underweight, and wasting among older children (>=24 months). No impact
      was observed among younger children (<24 months). CONCLUSIONS: Targeted resource
      transfers for families, augmented with a child sensitive social protection
      program and capacity building for social protection can address effectively child
      malnutrition. To increase the intervention effectiveness on younger children, the
      child cash payment amount needs to be revisited and closely embedded into infant
      and young child feeding initiatives, but also adjusted to equate to 20% of
      household expenditure or more to maximize the diversity of food available to
      young children.

PMID- 29207555
TI  - Study on Spatial Spillover Effects of Logistics Industry Development for Economic
      Growth in the Yangtze River Delta City Cluster Based on Spatial Durbin Model.
AB  - The overall entropy method is used to evaluate the development level of the
      logistics industry in the city based on a mechanism analysis of the spillover
      effect of the development of the logistics industry on economic growth, according
      to the panel data of 26 cities in the Yangtze River delta. On this basis, the
      paper uses the spatial durbin model to study the direct impact of the development
      of the logistics industry on economic growth and the spatial spillover effect.
      The results show that the direct impact coefficient of the development of the
      logistics industry in the Yangtze River Delta urban agglomeration on local
      economic growth is 0.092, and the significant spatial spillover effect on the
      economic growth in the surrounding area is 0.197. Compared with the labor force
      input, capital investment and the degree of opening to the world, and government
      functions, the logistics industry's direct impact coefficient is the largest,
      other than capital investment; the coefficient of the spillover effect is higher
      than other control variables, making it a "strong engine" of the Yangtze River
      Delta urban agglomeration economic growth.

PMID- 29207556
TI  - Effect of Low Cycle Fatigue Predamage on Very High Cycle Fatigue Behavior of TC21
      Titanium Alloy.
AB  - The effect of low cycle fatigue (LCF) predamage on the subsequent very high cycle
      fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF predamage is
      applied under 1.8% strain amplitude up to various fractions of the expected life
      and subsequent VHCF properties are determined using ultrasonic fatigue tests.
      Results show that 5% of predamage insignificantly affects the VHCF limit due to
      the absence of precrack, but decreases the subsequent fatigue crack initiation
      life estimated by the Pairs law. Precracks introduced by 10% and 20% of predamage
      significantly reduce the subsequent VHCF limits. The crack initiation site shifts
      from subsurface-induced fracture for undamaged and 5% predamaged specimens to
      surface precrack for 10% and 20% predamaged specimens in very high cycle region.
      Furthermore, the predicted fatigue limits based on the El Haddad modified model
      for the predamaged specimens agree with the experimental results.

PMID- 29207557
TI  - Lobocrassin B Induces Apoptosis of Human Lung Cancer and Inhibits Tumor Xenograft
      Growth.
AB  - Lobocrassin B, a natural cembrane-type compound isolated from the soft coral
      Lobophytum crassum, has been shown to have significant biological effects,
      including anticancer activity. As the most common cause of cancer mortality
      worldwide, lung cancer remains a major concern threatening human health. In the
      current study, we conducted in vitro experiments to demonstrate the inhibiting
      effect of Lobocrassin B on CL1-5 and H520 human lung cancer cells growth and to
      explore the underlying mechanisms, as well as in nude mice bearing CL1-5 tumor
      xenografts. Lobocrassin B exerted cytotoxic effects on lung cancer cells, as
      shown by decreasing cell viability, and inducing apoptosis, oxidative stress and
      mitochondrial dysfunction. In addition, the increased level of Bax, cleaved
      caspase-3, -9 and -8, and the suppression of Bcl-2 were observed in the
      Lobocrassin B treated cells. Moreover, in vivo assays verified the significance
      of these results, revealing that Lobocrassin B inhibited CL1-5 tumor xenograft
      growth and that inhibitory effects were accompanied by a marked increase in tumor
      cell apoptosis. In conclusion, the results suggested that Lobocrassin B could be
      a potential anticancer compound for its propensity to inhibit growth and induce
      apoptosis in human lung cancer cells.

PMID- 29207558
TI  - Three New Cytotoxic Steroidal Glycosides Isolated from Conus pulicarius Collected
      in Kosrae, Micronesia.
AB  - Three new sulfated steroidal glycosides (3-5), along with known cholesterol
      derivatives (1,2), were isolated from the visceral extract of the cone snail
      Conus pulicarius. The structure of each new compound was elucidated by nuclear
      magnetic resonance spectroscopy and high-resolution mass spectrometry. The three
      new compounds exhibited significant in vitro cytotoxicity (GI50 values down to
      0.49 MUM) against the K562 human leukemia cell line.

PMID- 29207559
TI  - Tooth Wear Is Frequent in Adult Patients with Celiac Disease.
AB  - (1) Background: Celiac disease (CD) patients can be affected by mouth and tooth
      disorders, which are influenced by their gluten-free diet. The aim of our
      research was to evaluate the pathological conditions of the stomatognathic system
      observed in celiac patients on a gluten-free diet. (2) Methods: we consecutively
      recruited celiac patients on a gluten-free diet at our celiac center, as well as
      healthy volunteers. Two dentists examined all patients/controls and checked them
      for any mouth disorder. (3) Results: Forty-nine patients affected by celiac
      disease (age at test 31.8 +/- 11.58, time on GFD 8.73 +/- 7.7) and 51 healthy
      volunteers (age at test 30.5 +/- 8.7) were included. Recurrent aphthous
      stomatitis was reported in 26 patients (53.0%) and in 13 (25.5%) controls (p =
      0.005). Dental enamel disorders were reported in 7 patients (14.3%) and in 0
      controls (p = 0.002), with none having geographic tongue. We found non-specific
      tooth wear, characterized by loss of the mineralized tissue of the teeth, in 9
      patients (18.3%) and in 3 (5.9%) controls (p = 0.05). (4) Conclusion: Recurrent
      aphthous stomatitis and enamel hypoplasia are "risk indicators" that may suggest
      that an individual has CD. We detected a high prevalence of non-specific tooth
      wear that can be caused by several factors such as malocclusion, sleep bruxism,
      parafunctional activity, and age.

PMID- 29207560
TI  - Optimization of Collagenase Production by Pseudoalteromonas sp. SJN2 and
      Application of Collagenases in the Preparation of Antioxidative Hydrolysates.
AB  - Collagenases are the most important group of commercially-produced enzymes.
      However, even though biological resources are abundant in the sea, very few of
      these commercially popular enzymes are from marine sources, especially from
      marine bacteria. We optimized the production of marine collagenases by
      Pseudoalteromonas sp. SJN2 and investigated the antioxidant activities of the
      hydrolysates. Media components and culture conditions associated with marine
      collagenase production by Pseudoalteromonas sp. SJN2 were optimized by
      statistical methods, namely Plackett-Burman design and response surface
      methodology (RSM). Furthermore, the marine collagenases produced by
      Pseudoalteromonas sp. SJN2 were seen to efficiently hydrolyze marine collagens
      extracted from fish by-products, and remarkable antioxidant capacities of the
      enzymatic hydrolysates were shown by DPPH radical scavenging and oxygen radical
      absorbance capacity (ORAC) tests. The final optimized fermentation conditions
      were as follows: soybean powder, 34.23 g.L-1; culture time, 3.72 d; and
      temperature, 17.32  degrees C. Under the optimal fermentation conditions, the
      experimental collagenase yield obtained was 322.58 +/- 9.61 U.mL-1, which was in
      agreement with the predicted yield of 306.68 U.mL-1. Collagen from Spanish
      mackerel bone, seabream scale and octopus flesh also showed higher DPPH radical
      scavenging rates and ORAC values after hydrolysis by the collagenase. This study
      may have implications for the development and use of marine collagenases.
      Moreover, seafood waste containing beneficial collagen could be used to produce
      antioxidant peptides by proteolysis.

PMID- 29207561
TI  - Cross-National Differences in Psychosocial Factors of Perinatal Depression: A
      Systematic Review of India and Japan.
AB  - Perinatal depression is prevalent worldwide. However, there are few available
      studies that discuss the different cultural factors affecting perinatal
      depression within Asian countries. This study aims to compare the literature
      regarding related factors relating to perinatal depression in India and Japan,
      and to synthesize the evidence common to both countries in addition to the
      country-specific evidence. We conducted a systematic review using several
      databases (CINAHL, MEDLINE, Pubmed, Ovid, SCOPUS, IndMED, and ICHUSI). Keywords
      were "antenatal depression" or "postpartum depression", and "India" or "Japan".
      Both Japanese and English language papers were reviewed. The identified evidence
      was compared between the two countries, as well as with non-Asian countries based
      on previous reports. In total, 15 articles on India and 35 on Japan were
      reviewed. Although several factors were shared between the two countries as well
      as with other non-Asian countries (vulnerable personality, being abused, age,
      marital conflict, and lower socio-demographic status), some differing factors
      were identified between India and Japan and non-Asian countries; India: poor
      socioeconomic status, living only with the husband, pregnancy not welcomed by the
      husband, a female baby, and poor relationship with in-laws; Japan: infertility
      treatment, conflict with work-life balance, poor relationships with biological
      mother or in-laws, and concerns about social relations with the other mother's
      friends. To conclude, involving the family and community may be important for
      implementing both global standardized and culture-specific interventions. In
      India, treatment involving the in-laws may be effective because large family
      structure is a significant predictor of perinatal depression. In Japan, a
      family/community approach involving not only the mother's family of origin but
      also the working environment is essential.

PMID- 29207562
TI  - The Impact of Technological Progress in the Energy Sector on Carbon Emissions: An
      Empirical Analysis from China.
AB  - This paper investigates the relationship between technological progress in the
      energy sector and carbon emissions based on the Environment Kuznets Curve (EKC)
      and data from China during the period of 1995-2012. Our study confirms that the
      situation in China conforms to the EKC hypothesis and presents the inverted U
      curve relationship between per capita income and carbon emissions. Furthermore,
      the inflection point will be reached in at least five years. Then, we use
      research and development (R & D) investment in the energy industry as the
      quantitative indicator of its technological progress to test its impact on carbon
      emissions. Our results show that technological progress in the energy sector
      contributes to a reduction in carbon emissions with hysteresis. Furthermore, our
      results show that energy efficiency improvements are also helpful in reducing
      carbon emissions. However, climate policy and change in industrial structure
      increase carbon emissions to some extent. Our conclusion demonstrates that
      currently, China is not achieving economic growth and pollution reduction
      simultaneously. To further achieve the goal of carbon reduction, the government
      should increase investment in the energy industry research and improve energy
      efficiency.

PMID- 29207563
TI  - Pyrene-Based Blue AIEgen: Enhanced Hole Mobility and Good EL Performance in
      Solution-Processed OLEDs.
AB  - Organic luminogens with strong solid-state emission have attracted much attention
      for their widely practical applications. However, the traditional organic
      luminogens with planar conformations often suffer from the notorious aggregation
      caused quenching (ACQ) effect in solid state for the pi-pi stacking. Here, a
      highly efficient blue emitter TPE-4Py with an aggregation-induced emission (AIE)
      effect is achieved by combining twisted tetraphenylethene (TPE) core and planar
      pyrene peripheries. When the emitter was spin-coated in non-doped OLEDs with or
      without a hole-transporting layer, comparable EL performance was achieved,
      showing the bifunctional property as both an emitter and a hole-transporting
      layer. Furthermore, its EL efficiency was promoted in doped OLED, even at a high
      doping concentration (50%), because of its novel AIE effect, with a current
      efficiency up to 4.9 cd/A at 484 nm.

PMID- 29207564
TI  - Obstacle Detection as a Safety Alert in Augmented Reality Models by the Use of
      Deep Learning Techniques.
AB  - Augmented reality (AR) is becoming increasingly popular due to its numerous
      applications. This is especially evident in games, medicine, education, and other
      areas that support our everyday activities. Moreover, this kind of computer
      system not only improves our vision and our perception of the world that
      surrounds us, but also adds additional elements, modifies existing ones, and
      gives additional guidance. In this article, we focus on interpreting a reality
      based real-time environment evaluation for informing the user about impending
      obstacles. The proposed solution is based on a hybrid architecture that is
      capable of estimating as much incoming information as possible. The proposed
      solution has been tested and discussed with respect to the advantages and
      disadvantages of different possibilities using this type of vision.

PMID- 29207565
TI  - Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure,
      Composition and Predicted Metabolic Function.
AB  - Cesarean (C-section) delivery, recently shown to cause excess weight gain in
      mice, perturbs human neonatal gut microbiota development due to the lack of
      natural mother-to-newborn transfer of microbes. Neonates excrete first the in
      utero intestinal content (referred to as meconium) hours after birth, followed by
      intestinal contents reflective of extra-uterine exposure (referred to as
      transition stool) 2 to 3 days after birth. It is not clear when the effect of C
      section on the neonatal gut microbiota emerges. We examined bacterial DNA in
      carefully-collected meconium, and the subsequent transitional stool, from 59
      neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a
      private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the
      16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA)
      platform. We found evidence of bacterial DNA in the majority of meconium samples
      in our study. The bacterial DNA structure (i.e., beta diversity) of meconium
      differed significantly from that of the transitional stool microbiota. There was
      a significant reduction in bacterial alpha diversity (e.g., number of observed
      bacterial species) and change in bacterial composition (e.g., reduced
      Proteobacteria) in the transition from meconium to stool. However, changes in
      predicted microbiota metabolic function from meconium to transitional stool were
      only observed in vaginally-delivered neonates. Within sample comparisons showed
      that delivery mode was significantly associated with bacterial structure,
      composition and predicted microbiota metabolic function in transitional-stool
      samples, but not in meconium samples. Specifically, compared to vaginally
      delivered neonates, the transitional stool of C-section delivered neonates had
      lower proportions of the genera Bacteroides, Parabacteroides and Clostridium.
      These differences led to C-section neonates having lower predicted abundance of
      microbial genes related to metabolism of amino and nucleotide sugars, and higher
      abundance of genes related to fatty-acid metabolism, amino-acid degradation and
      xenobiotics biodegradation. In summary, microbiota diversity was reduced in the
      transition from meconium to stool, and the association of delivery mode with
      microbiota structure, composition and predicted metabolic function was not
      observed until the passing of the transitional stool after meconium.

PMID- 29207566
TI  - The Osteogenic and Tenogenic Differentiation Potential of C3H10T1/2 (Mesenchymal
      Stem Cell Model) Cultured on PCL/PLA Electrospun Scaffolds in the Absence of
      Specific Differentiation Medium.
AB  - The differentiation potential of mesenchymal stem cells (MSC) has been
      extensively tested on electrospun scaffolds. However, this potential is often
      assessed with lineage-specific medium, making it difficult to interpret the real
      contribution of the properties of the scaffold in the cell response. In this
      study, we analyzed the ability of different polycaprolactone/polylactic acid
      PCL/PLA electrospun scaffolds (pure or blended compositions, random or aligned
      fibers, various fiber diameters) to drive MSC towards bone or tendon lineages in
      the absence of specific differentiation medium. C3H10T1/2 cells (a mesenchymal
      stem cell model) were cultured on scaffolds for 96 h without differentiation
      factors. We performed a cross-analysis of the cell-scaffold interactions
      (spreading, organization, and specific gene expression) with mechanical
      (elasticity), morphological (porosity, fibers diameter and orientation) and
      surface (wettability) characterizations of the electrospun fibers. We concluded
      that (1) osteogenic differentiation can be initiated on pure PCL-based
      electrospun scaffolds without specific culture conditions; (2) fiber alignment
      modified cell organization in the short term and (3) PLA added to PCL with an
      increased fiber diameter encouraged the stem cells towards the tendon lineage
      without additional tenogenic factors. In summary, the differentiation potential
      of stem cells on adapted electrospun fibers could be achieved in factor-free
      medium, making possible future applications in clinically relevant situations.

PMID- 29207567
TI  - Synthesis and Antibacterial Evaluation of a Series of 11,12-Cyclic Carbonate
      Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives.
AB  - A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O
      carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for
      their antibacterial activities in vitro. Most of these compounds had significant
      antibacterial activity against seven kinds of susceptible strains. In particular,
      compound G1 exhibited the most potent activity against methicillin-resistant
      Streptococcus pneumoniae 943 (MIC: 1 MUg/mL), Staphylococcus pneumoniae 746 (MIC:
      2 MUg/mL), Streptococcus pyogenes 447 (MIC: 8 MUg/mL), and Escherichia coli 236
      (MIC: 32 MUg/mL), which were two-, four-, four-, four-, and eight-fold stronger
      activity than azithromycin, respectively. Additionally, compound G2 exhibited
      improved activity against methicillin-resistant Staphylococcus aureus MRSA-1
      (MIC: 8 MUg/mL), Streptococcus pneumoniae 943 (MIC: 2 MUg/mL), Staphylococcus
      pneumoniae 746 (MIC: 2 MUg/mL), and Escherichia coli 236 (MIC: 32 MUg/mL), which
      were two-, two-, four-, and eight-fold better activity than azithromycin,
      respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound
      G6 presented the most excellent activity (MIC: 4 MUg/mL), showing four-fold
      higher activity than azithromycin (MIC: 16 MUg/mL) and erythromycin (MIC: 16
      MUg/mL). However, compared with other compounds, compounds G7 and G8 with the
      disaccharide side chain were observed the lower activity against seven strains.

PMID- 29207568
TI  - Recent Advances in Fluorescence Lifetime Analytical Microsystems: Contact Optics
      and CMOS Time-Resolved Electronics.
AB  - Fluorescence spectroscopy has become a prominent research tool with wide
      applications in medical diagnostics and bio-imaging. However, the realization of
      combined high-performance, portable, and low-cost spectroscopic sensors still
      remains a challenge, which has limited the technique to the laboratories. A
      fluorescence lifetime measurement seeks to obtain the characteristic lifetime
      from the fluorescence decay profile. Time-correlated single photon counting
      (TCSPC) and time-gated techniques are two key variations of time-resolved
      measurements. However, commercial time-resolved analysis systems typically
      contain complex optics and discrete electronic components, which lead to
      bulkiness and a high cost. These two limitations can be significantly mitigated
      using contact sensing and complementary metal-oxide-semiconductor (CMOS)
      implementation. Contact sensing simplifies the optics, whereas CMOS technology
      enables on-chip, arrayed detection and signal processing, significantly reducing
      size and power consumption. This paper examines recent advances in contact
      sensing and CMOS time-resolved circuits for the realization of fully integrated
      fluorescence lifetime measurement microsystems. The high level of performance
      from recently reported prototypes suggests that the CMOS-based contact sensing
      microsystems are emerging as sound technologies for application-specific, low
      cost, and portable time-resolved diagnostic devices.

PMID- 29207569
TI  - The UV Plasmonic Behavior of Distorted Rhodium Nanocubes.
AB  - For applications of surface-enhanced spectroscopy and photocatalysis, the
      ultraviolet (UV) plasmonic behavior and charge distribution within rhodium
      nanocubes is explored by a detailed numerical analysis. The strongest plasmonic
      hot-spots and charge concentrations are located at the corners and edges of the
      nanocubes, exactly where they are the most spectroscopically and catalytically
      active. Because intense catalytic activity at corners and edges will reshape
      these nanoparticles, distortions of the cubical shape, including surface
      concavity, surface convexity, and rounded corners and edges, are also explored to
      quantify how significantly these distortions deteriorate their plasmonic and
      photocatalytic properties. The fact that the highest fields and highest carrier
      concentrations occur in the corners and edges of Rh nanocubes (NCs) confirms
      their tremendous potential for plasmon-enhanced spectroscopy and catalysis. It is
      shown that this opportunity is fortuitously enhanced by the fact that even higher
      field and charge concentrations reside at the interface between the metal
      nanoparticle and a dielectric or semiconductor support, precisely where the most
      chemically active sites are located.

PMID- 29207571
TI  - Computational Modelling of Structures with Non-Intuitive Behaviour.
AB  - This paper presents a finite-element analysis of honeycomb and re-entrant
      honeycomb structures made of a two-phase composite material which is optimized
      with respect to selected parameters. It is shown that some distributions of each
      phase in the composite material result in the counter-intuitive mechanical
      behaviour of the structures. In particular, negative values of effective
      Poisson's ratio, i.e., effective auxeticity, can be obtained for a hexagonal
      honeycomb, whereas re-entrant geometry can be characterized by positive values.
      Topology optimization by means of the method of moving asymptotes (MMA) and solid
      isotropic material with penalization (SIMP) was used to determine the materials'
      distributions.

PMID- 29207570
TI  - Low Levels of Physical Activity and Sedentary Behavior in Adults with
      Intellectual Disabilities.
AB  - Adults with intellectual disabilities (ID) are more likely to lead sedentary
      lifestyles and have low levels of physical activity (LLPA). The present study
      investigated the prevalence of reported LLPA and time spent watching TV in adults
      with ID and identified the associated factors for these behaviors. The proxy
      informants of 1618 adults with ID completed the surveys regarding their health
      behaviors. Multiple logistic regressions were employed for LLPA and multiple
      linear regressions for time spent watching TV. About 60% of adults with ID had
      LLPA and average time spent watching TV was 3.4 h a day. Some characteristics and
      health and function variables were identified as associated factors. While
      engaging in community activities and involvement in Special Olympics were
      inversely associated with LLPA, they were not associated with time spent watching
      TV. Attending day/educational programs or being employed were associated with
      spending less time watching TV. Findings highlight differential factors
      associated with LLPA versus TV-watching behavior in adults with ID. Hence, a key
      strategy aimed at increasing physical activity includes promoting participation
      in social and community activities, while targeted activities for reducing
      sedentary behavior might focus on providing day programs or employment
      opportunities for adults with ID.

PMID- 29207572
TI  - Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power
      and Sample Size.
AB  - Biomarker-guided clinical trial designs, which focus on testing the effectiveness
      of a biomarker-guided approach to treatment in improving patient health, have
      drawn considerable attention in the era of stratified medicine with many
      different designs being proposed in the literature. However, planning such trials
      to ensure they have sufficient power to test the relevant hypotheses can be
      challenging and the literature often lacks guidance in this regard. In this
      study, we focus on the parallel subgroup-specific design, which allows the
      evaluation of separate treatment effects in the biomarker-positive subgroup and
      biomarker-negative subgroup simultaneously. We also explore an adaptive version
      of the design, where an interim analysis is undertaken based on a fixed
      percentage of target events, with the option to stop each biomarker-defined
      subgroup early for futility or efficacy. We calculate the number of events and
      patients required to ensure sufficient power in each of the biomarker-defined
      subgroups under different scenarios when the primary outcome is time-to-event.
      For the adaptive version, stopping probabilities are also explored. Since
      multiple hypotheses are being tested simultaneously, and multiple interim
      analyses are undertaken, we also focus on controlling the overall type I error
      rate by way of multiplicity adjustment.

PMID- 29207573
TI  - The Effects of Industrial Protective Gloves and Hand Skin Temperatures on Hand
      Grip Strength and Discomfort Rating.
AB  - Daily working activities and functions require a high contribution of hand and
      forearm muscles in executing grip force. To study the effects of wearing
      different gloves on grip strength, under a variety of hand skin temperatures, an
      assessment of the maximum grip strength was performed with 32 healthy male
      workers with a mean age (standard deviation) of 30.44 (5.35) years wearing five
      industrial gloves at three hand skin temperatures. Their ages and anthropometric
      characteristics including body mass index (BMI), hand length, hand width, hand
      depth, hand palm, and wrist circumference were measured. The hand was exposed to
      different bath temperatures (5  degrees C, 25  degrees C, and 45  degrees C) and
      hand grip strength was measured using a Jamar hydraulic hand dynamometer with and
      without wearing the gloves (chemical protection glove, rubber insulating glove,
      anti-vibration impact glove, cotton yarn knitted glove, and RY-WG002 working
      glove). The data were analyzed using the Shapiro-Wilk test, Pearson correlation
      coefficient, Tukey test, and analysis of variance (ANOVA) of the within-subject
      design analysis. The results showed that wearing gloves significantly affected
      the maximum grip strength. Wearing the RY-WG002 working glove produced a greater
      reduction on the maximum grip when compared with the bare hand, while low
      temperatures (5  degrees C) had a significant influence on grip when compared to
      medium (25  degrees C) and high (45  degrees C) hand skin temperatures. In
      addition, participants felt more discomfort in both environmental extreme
      conditions. Furthermore, they reported more discomfort while wearing neoprene,
      rubber, and RY-WG002 working gloves.

PMID- 29207574
TI  - Novel Carbazole Skeleton-Based Photoinitiators for LED Polymerization and LED
      Projector 3D Printing.
AB  - Radical chemistry is a very convenient way to produce polymer materials. Here, an
      application of a particular photoinduced radical chemistry is illustrated. Seven
      new carbazole derivatives Cd1-Cd7 are incorporated and proposed as high
      performance near-UV photoinitiators for both the free radical polymerization
      (FRP) of (meth)acrylates and the cationic polymerization (CP) of epoxides
      utilizing Light Emitting Diodes LEDs @405 nm. Excellent polymerization-initiating
      abilities are found and high final reactive function conversions are obtained.
      Interestingly, these new derivatives display much better near-UV polymerization
      initiating abilities compared to a reference UV absorbing carbazole (CARET 9H
      carbazole-9-ethanol) demonstrating that the new substituents have good ability to
      red shift the absorption of the proposed photoinitiators. All the more
      strikingly, in combination with iodonium salt, Cd1-Cd7 are likewise preferred as
      cationic photoinitiators over the notable photoinitiator bis(2,4,6
      trimethylbenzoyl)phenylphosphine oxide (BAPO) for mild irradiation conditions
      featuring their remarkable reactivity. In particular their utilization in the
      preparation of new cationic resins for LED projector 3D printing is envisioned. A
      full picture of the included photochemical mechanisms is given.

PMID- 29207575
TI  - Synthesis of Novel Nitrogen-Containing Heterocycle Bromophenols and Their
      Interaction with Keap1 Protein by Molecular Docking.
AB  - We previously reported 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanoe (LM49), a
      bromophenol analogue that shows strong protection from oxidative stress injury
      owing to its superior anti-inflammatory, antioxidant, and anti-apoptotic
      properties. A series of novel nitrogen-containing heterocycle bromophenols were
      herein synthesized by introducing substituted piperidine, piperazine, and
      imidazole to modify 2-position of the lead compound LM49. By further evaluating
      their cytoprotective activity against H2O2 induced injury in EA.hy926 cells, 14
      target bromophenols showed moderate-to-potent activity with EC50 values in the
      range of 0.9-6.3 MUM, which were stronger than that of quercetin (EC50: 18.0
      MUM), a positive reference compound. Of these, the most potent compound 22b is a
      piperazine bromophenol with an EC50 value of 0.9 MUM equivalent to the LM49.
      Molecular docking studies were subsequently performed to deduce the affinity and
      binding mode of derived halophenols toward the Keap1 Kelch domain, the docking
      results exhibited that the small molecule 22b is well accommodated by the bound
      region of Keap1-Kelch and Nrf2 through stable hydrogen bonds and hydrophobic
      interaction, which contributed to the enhancement of affinity and stability
      between the ligand and receptor. The above facts suggest that 22b is a promising
      pharmacological candidate for further cardiovascular drug development. Moreover,
      the targeting Keap1-Nrf2 protein-protein interaction may be an emerging strategy
      for halophenols to selectively and effectively activate Nrf2 triggering
      downstream protective genes defending against injury.

PMID- 29207577
TI  - Replication stress in colorectal cancer stem cells.

PMID- 29207576
TI  - Glycosaminoglycan-Mediated Downstream Signaling of CXCL8 Binding to Endothelial
      Cells.
AB  - The recruitment of leukocytes, mediated by endothelium bound chemokine gradients,
      is a vital process in inflammation. The highly negatively charged, unbranched
      polysaccharide family of glycosaminoglycans (GAGs), such as heparan sulfate and
      chondroitin sulfate mediate chemokine immobilization. Specifically the binding of
      CXCL8 (interleukin 8) to GAGs on endothelial cell surfaces is known to regulate
      neutrophil recruitment. Currently, it is not clear if binding of CXCL8 to GAGs
      leads to endothelial downstream signaling in addition to the typical CXCR1/CXCR2
      (C-X-C motif chemokine receptor 1 and 2)-mediated signaling which activates
      neutrophils. Here we have investigated the changes in protein expression of human
      microvascular endothelial cells induced by CXCL8. Tumor necrosis factor alpha
      (TNFalpha) stimulation was used to mimic an inflammatory state which allowed us
      to identify syndecan-4 (SDC4) as the potential proteoglycan co-receptor of CXCL8
      by gene array, real-time PCR and flow cytometry experiments. Enzymatic GAG
      depolymerization via heparinase III and chondroitinase ABC was used to emulate
      the effect of glycocalyx remodeling on CXCL8-induced endothelial downstream
      signaling. Proteomic analyses showed changes in the expression pattern of a
      number of endothelial proteins such as Zyxin and Caldesmon involved in
      cytoskeletal organization, cell adhesion and cell mobility. These results
      demonstrate for the first time a potential role of GAG-mediated endothelial
      downstream signaling in addition to the well-known CXCL8-CXCR1/CXCR2 signaling
      pathways in neutrophils.

PMID- 29207578
TI  - Molecular insights into desmoid tumors.

PMID- 29207579
TI  - Circulating tumour DNA analysis in multiple myeloma.

PMID- 29207580
TI  - Targeting the value of targeted therapy.

PMID- 29207581
TI  - Targeting multiple nodes of MLL complexes to improve leukemia therapy.

PMID- 29207582
TI  - Our young cancer patients talk-we learn.

PMID- 29207583
TI  - Autologous transplant for myeloma: when the old meets the new.

PMID- 29207584
TI  - miR-301a mediated immune evasion by Japanese encephalitis virus.

PMID- 29207585
TI  - Multifaceted CK2 in malignant and healthy T cells.

PMID- 29207586
TI  - Targeting autoreactive germinal centers to curb autoimmunity.

PMID- 29207587
TI  - Cobll1: A new player in CML.

PMID- 29207588
TI  - Traceback: leveraging archived biospecimens to identify mutation carriers.

PMID- 29207589
TI  - Tolerogenic dendritic cell-based immunotherapy.

PMID- 29207590
TI  - Microvesicles in CLL: predictor of disease progression/relapse.

PMID- 29207591
TI  - Integrative cancer care: crossing communication barriers.

PMID- 29207592
TI  - Unproven stem cell therapy for macular degeneration.

PMID- 29207593
TI  - Deregulated c-Myc requires a functional HSF1 for experimental and human
      hepatocarcinogenesis.
AB  - Deregulated activity of the c-Myc protooncogene is a frequent molecular event
      underlying mouse and human hepatocarcinogenesis. Nonetheless, the mechanisms
      sustaining c-Myc oncogenic activity in liver cancer remain scarcely delineated.
      Recently, we showed that the mammalian target of rapamycin complex 1 (mTORC1)
      cascade is induced and necessary for c-Myc dependent liver tumor development and
      progression. Since the heat shock factor 1 (HSF1) transcription factor is a major
      positive regulator of mTORC1 in the cell, we investigated the functional
      interaction between HSF1 and c-Myc using in vitro and in vivo approaches. We
      found that ablation of HSF1 restrains the growth of c-Myc-derived mouse
      hepatocellular carcinoma (HCC) cell lines, where it induces downregulation of c
      Myc levels. Conversely, silencing of c-Myc gene in human and mouse HCC cells led
      to downregulation of HSF1 expression. Most importantly, overexpression of a
      dominant negative form of HSF1 (HSF1dn) in the mouse liver via hydrodynamic gene
      delivery resulted in the complete inhibition of mouse hepatocarcinogenesis driven
      by overexpression of c-Myc. Altogether, the present results indicate that a
      functional HSF1 is necessary for c-Myc-driven hepatocarcinogenesis. Consequently,
      targeting HSF1 might represent a novel and effective therapeutic strategy for the
      treatment of HCC subsets with activated c-Myc signaling.

PMID- 29207594
TI  - Cancer-mutated ribosome protein L22 (RPL22/eL22) suppresses cancer cell survival
      by blocking p53-MDM2 circuit.
AB  - Several ribosomal proteins (RPs) in response to various ribosomal stressors have
      been shown to play a critical role in p53-dependent regulation of cell cycle
      arrest, apoptosis and tumor suppression. Here, we report ribosomal protein L22
      (RPL22/eL22) as a novel p53 activator highly mutated (mostly deletion mutation)
      in various types of human cancers, but not essential for ribosomal biogenesis in
      normal cells. Ectopic expression of RPL22/eL22 suppressed the colony formation of
      cancer cells in a p53-dependent manner, whereas knockdown of RPL22/eL22
      significantly compromised p53 activation by Actinomycin D, rescuing p53-induced
      G1/G0 cell cycle arrest. Interestingly, human tumors with RPL22/eL22 deletion
      appeared to sustain wild type p53. Mechanistically, RPL22/eL22 bound to MDM2
      acidic domain and inhibited MDM2-mediated p53 ubiquitination and degradation,
      hence extending the half-life of p53. Ribosome-profiling analysis revealed that
      induction of ribosomal stress by Actinomycin D leads to the increase of ribosome
      free RPL22/eL22 pool. Also, RPL22/eL22 formed a complex with
      MDM2/RPL5/uL18/RPL11/uL5 and synergized with RPL11/uL5 to activate p53.
      Furthermore, the N terminus of RPL22/eL22 bound to MDM2, while the C terminus
      interacted with RPL5/uL18/RPL11/uL5; both of these two fragments activated p53 by
      inhibiting MDM2. Our study indicates that RPL22/eL22 highly mutated in human
      cancers plays an anti-cancer role likely through regulation of the MDM2-p53
      feedback loop, and also suggests that targeting the RPL22/eL22-MDM2-p53 pathway
      could be a potential strategy for future development of anti-cancer therapy.

PMID- 29207595
TI  - CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA
      damaging therapeutic agents.
AB  - Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a
      vital role in many biological events including cell cycle control, DNA damage
      repair, and checkpoint activation. Here, we identify an unanticipated role for
      CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short
      duration of CDK1 inhibition, which does not perturb cell cycle progression,
      triggers a replication-associated DNA damage response (DDR). This DDR is
      associated with a disruption of replication fork progression and leads to genome
      instability. Moreover, we show that compromised CDK1 activity dramatically
      increases the efficacy of chemotherapeutic agents that kill cancer cells through
      perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor.
      Our study has revealed an important role for CDK1 in the DNA replication program,
      and suggests that the therapeutic targeting CDK1 may be a novel approach for
      combination chemotherapy.

PMID- 29207596
TI  - UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3sigma axis inhibits
      keratinocyte survival and proliferation.
AB  - Understanding protein subcellular localization is important to determining the
      functional role of specific proteins. T-cell protein tyrosine phosphatase (TC
      PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C
      terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45)
      is mainly localized to the cytoplasm in keratinocytes and it is translocated to
      the nucleus following UVB irradiation. Here, we report that TC45 is translocated
      by an AKT/14-3-3sigma-mediated mechanism in response to UVB exposure, resulting
      in increased apoptosis and decreased keratinocyte proliferation. We demonstrate
      that UVB irradiation increased phosphorylation of AKT and induced nuclear
      translocation of 14-3-3sigma and TC45. However, inhibition of AKT blocked nuclear
      translocation of TC45 and 14-3-3sigma. Site-directed mutagenesis of 14-3-3sigma
      binding sites within TC45 showed that a substitution at Threonine 179
      (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic
      TC45 due to the disruption of the direct binding between TC45 and 14-3-3sigma.
      Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB
      induced apoptosis which corresponded to an increase in nuclear phosphorylated
      STAT3, and cell proliferation was higher in TC45/T179A-overexpressing
      keratinocytes compared to control keratinocytes following UVB irradiation.
      Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear
      translocation, indicating that both T179 and NLSII are required. Taken together,
      our findings suggest that AKT and 14-3-3sigma cooperatively regulate TC45 nuclear
      translocation in a critical step of an early protective mechanism against UVB
      exposure that signals the deactivation of STAT3 in order to promote keratinocyte
      cell death and inhibit keratinocyte proliferation.

PMID- 29207597
TI  - Inhibition of Miro1 disturbs mitophagy and pancreatic beta-cell function
      interfering insulin release via IRS-Akt-Foxo1 in diabetes.
AB  - Mitochondrial function is essential to meet metabolic demand of pancreatic beta
      cells respond to high nutrient stress. Mitophagy is an essential component to
      normal pancreatic beta-cell function and has been associated with beta-cell
      failure in Type 2 diabetes (T2D). Our previous studies have indicated that
      mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high
      nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory
      responses and subsequent insulin resistance. However, the in vivo mechanism by
      which Miro1 underlies mitophagy has not been identified. Here we show firstly
      that the expression of Miro is reduced in human T2D and mouse db/db islets and in
      INS-1 cell line exposed to high glucose and palmitate. beta-cell specific
      ablation of Miro1 (Miro1f/f: Rip-cre mice, or (IKO) under high nutrient stress
      promotes the development of hyperglycemia. beta-cells from IKO mice display an
      inhibition of mitophagy under oxidative stress and induces mitochondrial
      dysfunction. Dysfunctional mitophagy in IKO mice is represented by damaged islet
      beta cell mitochondrial and secretory capacity, unbalanced downstream MKK-JNK
      signalling without affecting the levels of MEK, ERK or p38 activation and
      subsequently, impaired insulin secretion signaling via inhibition IRS-AKT-Foxo1
      pathway, leading to worsening glucose tolerance in these mice. Thus, these data
      suggest that Miro1 may be responsible for mitophagy deficiency and beta-cell
      dysfunction in T2D and that strategies target Miro1 in vivo may provide a
      therapeutic target to enhance beta-cell mitochondrial quality and insulin
      secretion to ameliorate complications associated with T2D.

PMID- 29207598
TI  - Low expression of SerpinB2 is associated with reduced survival in lung
      adenocarcinomas.
AB  - : Lung cancer is a leading cause of cancer deaths worldwide and new biomarkers
      are of utmost importance. Studies have indicated that the anti-plasminogen
      activators SerpinB2 and Neuroserpin, and the adhesion molecule L1CAM, have a
      coordinated impact on development of metastasis. Here, we examined whether
      expression of these markers was associated with clinico-pathologic
      characteristics and prognosis in resected non-small cell lung cancer (NSCLC).
      Surgical specimens from 438 NSCLC patients treated at Haukeland University
      Hospital, Bergen, Norway (1993-2010) were included (median age 68 years; 213
      adenocarcinomas, 135 squamous cell carcinomas, 90 others). Representative tumor
      sections were stained for SerpinB2, Neuroserpin, and L1CAM. Low expression of
      SerpinB2 was associated with reduced lung cancer specific survival (LCSS) in
      adenocarcinomas (p = 0.017), also in stage I (p = 0.031). In contrast, high
      SerpinB2 was associated with reduced LCSS in stage I squamous cell carcinomas (p
      = 0.022). Although Neuroserpin and L1CAM showed some associations with clinico
      pathologic phenotype, there were no associations with survival. In multivariate
      survival analysis of adenocarcinomas, low SerpinB2 demonstrated independent
      prognostic value (HR 1.8, p = 0.008). In summary, low expression of SerpinB2 in
      lung adenocarcinomas was an independent prognostic factor. In contrast to
      findings by others, we found no impact of L1CAM on survival. INTRODUCTION: 

PMID- 29207599
TI  - Automated histological classification of whole slide images of colorectal biopsy
      specimens.
AB  - Background: An automated image analysis system, e-Pathologist, was developed to
      improve the quality of colorectal biopsy diagnostics in routine pathology
      practice. Objective: The aim of the study was to evaluate the classification
      accuracy of the e-Pathologist image analysis software in the setting of routine
      pathology practice in two institutions. Materials and methods: In total, 1328
      colorectal tissue specimens were consecutively obtained from two hospitals (1077
      tissues from Tokyo hospital, and 251 tissues from East hospital) and the stained
      specimen slides were anonymized and digitized. At least two experienced
      gastrointestinal pathologists evaluated each slide for pathological diagnosis. We
      compared the 3-tier classification results (carcinoma or suspicion of carcinoma,
      adenoma, and lastly negative for a neoplastic lesion) between the human
      pathologists and that of e-Pathologist. Results: For the Tokyo hospital
      specimens, all carcinoma tissues were correctly classified (n=112), and 9.9%
      (80/810) of the adenoma tissues were incorrectly classified as negative. For the
      East hospital specimens, 0 out of the 51 adenoma tissues were incorrectly
      classified as negative while 9.3% (11/118) of the carcinoma tissues were
      incorrectly classified as either adenoma, or negative. For the Tokyo and East
      hospital datasets, the undetected rate of carcinoma, undetected rate of adenoma,
      and over-detected proportion were 0% and 9.3%, 9.9% and 0%, and 36.1% and 27.1%,
      respectively. Conclusions: This image analysis system requires some improvements;
      however, it has the potential to assist pathologists in quality improvement of
      routine pathological practice in the not too distant future.

PMID- 29207600
TI  - Host cell transcriptome modification upon exogenous HPV16 L2 protein expression.
AB  - Human papillomavirus type 16 minor capsid protein L2 has been shown to assist in
      the initial entry and intracellular trafficking events leading to nuclear
      translocation of the viral genome. During our investigations of L2 function, we
      observed that expression of L2 in a keratinocyte cell line (HaCaT) resulted in
      phenotypic changes. In this manuscript, we present data that expression of the L2
      protein in this cellular model system HaCaTs resulted in a shift from G0/G1 phase
      to mitotic S phase, as well as a reduced amount of retinoblastoma protein (Rb)
      and an increase in Cdc2 phosphorylation. We performed genome-wide host cell mRNA
      sequencing and identified 2586 differentially expressed genes upon HPV16 L2
      expression. Via machine learning and protein network analysis, genes involved in
      cellular differentiation and proliferation were highlighted as impacted by L2.
      Our results have implications for the role of L2 at the viral production stages
      when the virus needs to prevent cellular differentiation while maintaining the
      cells ability to replicate DNA. Our study suggests a potential novel function of
      the L2 protein, as a regulator of cellular gene transcription.

PMID- 29207601
TI  - Dissecting the mechanisms involved in anti-human T-lymphocyte immunoglobulin
      (ATG)-induced tolerance in the setting of allogeneic stem cell transplantation -
      potential implications for graft versus host disease.
AB  - Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to
      significantly reduce the incidence of graft versus host disease (GVHD) post
      allogeneic stem cell transplantation (HSCT) from both sibling and unrelated
      donors. Induction of regulatory T cells has been suggested as one of the possible
      mechanisms. The aim of current study was to further characterize the T cell
      populations induced by ATG treatment and to delineate the mechanisms involved in
      ATG-induced tolerance. Phenotypic characterization revealed a significant
      increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the
      complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG
      treatment. Addition of ATG-treated cells to autologous and allogeneic peripheral
      blood mononuclear cells (PBMCs) stimulated with anti-CD3/anti-CD28 antibodies
      resulted in significant inhibition of proliferation. Moreover, T-cell activation
      and IFNgamma secretion were reduced in the presence of ATG-induced Treg cells.
      The CD4+CD25+CD127-low Treg fraction sorted from ATG-treated culture demonstrated
      greater suppressive potency than negative fraction. Conditioned medium produced
      by ATG-treated but not IgG-treated cells contained TGFbeta and suppressed T cell
      proliferation and activation in a TGFbeta receptor-dependent manner. TGFbeta
      receptor kinase inhibitor SB431542 interfered with the suppressive activity of
      ATG-primed cells, enabling partial rescue of proliferation and IFNgamma
      secretion. Moreover, SB431542 prevented Treg phenotype induction upon ATG
      treatment. Altogether, our data reveal the role of TGFbeta signaling in ATG
      mediated immunosuppression and further support the use of ATG, a potent inducer
      of regulatory T cells, for prevention of GVHD post HSCT and potentially other
      therapeutic applications.

PMID- 29207602
TI  - The TRPV1 ion channel regulates thymocyte differentiation by modulating autophagy
      and proteasome activity.
AB  - Autophagy and the ubiquitin-proteasome system (UPS) control thymus cell
      homeostasis under resting and endoplasmic reticulum (ER) stress conditions.
      Several evidence support a cross-talk between UPS and autophagy; abrogation of
      UPS responses stimulates autophagy, and vice versa the inhibition of autophagy
      alters the UPS functions. Herein, we found that TRPV1 activation induces ER
      stress, proteasome dysfunction and autophagy in thymocytes by modulating the
      expression of UPR-related genes. The TRPV1-mediated autophagy prevents the UPR
      activation by inhibiting BiP, Grp94 and ERp57 chaperone protein expression.
      Thymocytes from TRPV1 KO mice display both autophagy and proteasome dysfunctions,
      resulting in increased apoptotic cells and reduced total DP thymocyte number. In
      addition, positive selection of thymocytes triggered by anti-TCRbeta/CD2 Ab
      mediated costimulation induces apoptosis in thymocytes from TRPV1 KO as compared
      with WT mice. Stimulation of TRPV1 KO thymocytes with anti-TCRbeta/CD2 mAbs
      modulates the expression of CD4 antigen on purified DP thymocytes, with reduced
      number of mature, single positive (SP) CD4 and increased number of immature SP
      CD4low and DP CD4lowCD8+ thymocytes, further supporting the intrinsic role of
      TRPV1 in T cell maturation. Finally, a reduction in CD8+ and CD4+ T cells is
      evidenced in the peripheral blood and spleen of TRPV1 KO, as compared with WT
      mice. Therapeutic strategy by restraining or stimulating the TRPV1 expression and
      functions in thymocytes might represent a new pharmacological tool in the
      regulation of different inflammatory T cell responses.

PMID- 29207604
TI  - Canis familiaris allergen Can f 6: expression, purification and analysis of B
      cell epitopes in Chinese dog allergic children.
AB  - Dog allergy is common worldwide. However, the allergenicity of dog allergy is
      still unclear in China as well as in special group, such as children. In this
      study, we chose Can f 6, a major dog allergen which belongs to the lipocalin to
      study its allergenicity in Chinese dog allergic children. Can f 6 gene was
      subcloned into pET-28a vector and transformed into E. coli BL21 (DE3) cells for
      expression. The recombinant Can f 6 was purified by nickel affinity
      chromatography, identified by SDS-PAGE, and tested for its allergenicity by
      Western blot with sera and basophil activation test. Secondary structures, B cell
      epitopes and homology modeling of Can f 6 were predicted by using a series of
      bioinformatical approaches. And the verification of B cell epitopes was detected
      by ELISA. The recombinant allergen showed an explicit band with the molecular
      weight of 20 kDa by SDS-PAGE. Sera from 56.3 % (18/32) of dog-allergic children
      patients reacted with Can f 6. The induction of the expression of CD63 and CCR3
      of dog allergic children in passively sensitized basophils was up to
      approximately 5.0 times higher than healthy subjects. The secondary structure of
      Can f 6 contains 3 alpha-helices, 9 beta-sheets and random coils. Five B cell
      epitopes of Can f 6 were predicted and were confirmed successfully by ELISA. The
      results showed Can f 6 is a major allergen in Chinese children, which provides a
      basis for further study of Can f 6 in diagnosis and treatment of symptoms in
      children in China. The structural information of Can f 6 will help to form a
      foundation for the future design of vaccines and therapies for Can f 6 related
      allergies.

PMID- 29207603
TI  - Effects of baicalein on IL-1beta-induced inflammation and apoptosis in rat
      articular chondrocytes.
AB  - In osteoarthritis (OA), activated synoviocytes and articular chondrocytes produce
      pro-inflammatory cytokines, such as IL-1beta, that promote chondrocyte apoptosis
      and activate the NF-kappaB signaling pathway to induce catabolic factors. In this
      study, we examined the anti-inflammatory and anti-apoptotic effect of baicalein
      on IL-1beta signaling and NF-kappaB-regulated gene products in rat chondrocytes.
      Rat chondrocytes were pretreated with 10 ng/ml IL-1beta for 24 h and then co
      treated with 10 ng/ml IL-1beta and 50 MUM baicalein for 0, 12, 24, 36 and 48h.
      The expression levels of poly(ADP-ribose) polymerase (PARP), Bcl-2, caspase-3,
      matrix metalloproteinase (MMP)-9, MMP-3, cyclooxygenase (COX)-2 and SOX-9 were
      detected by Western blot and quantitative reverse transcription-PCR (qPCR). The
      effects of baicalein on the translocation and phosphorylation of the NF-kappaB
      system were studied by Western blotting and immunofluorescence. Baicalein
      stimulated the expression of anti-apoptotic genes and reduced the pro-apoptotic
      and pro-inflammatory gene products in chondrocytes. Baicalein promoted SOX-9
      expression in a time-dependent manner in chondrocytes. Baicalein inhibited the NF
      kappaB activation that was induced by IL-1beta in a time-dependent manner in
      chondrocytes. Our results suggest that the anti-inflammatory and anti-apoptotic
      effects of baicalein are mediated through the inhibition of the translocation of
      phosphorylated p65 to the nucleus.

PMID- 29207605
TI  - VEGF121, is predictor for survival in activated B-cell-like diffuse large B-cell
      lymphoma and is related to an immune response gene signature conserved in
      cancers.
AB  - Tumor microenvironment including endothelial and immune cells plays a crucial
      role in tumor progression and has been shown to dramatically influence cancer
      survival. In this study, we investigated the clinical relevance of the gene
      expression of key mediators of angiogenesis, VEGF isoforms 121, 165, and 189, and
      their receptors (VEGFR-1 and R-2) in a cohort of patients (n = 37) with
      relapsed/refractory diffuse large B-cell lymphoma (DLBCL) from the Collaborative
      Trial in Relapsed Aggressive Lymphoma (CORAL). In patients with ABC-like DLBCL,
      but not in patients with GCB-like DLBCL, low VEGF121 expression was associated
      with a significantly better survival than in those with high VEGF121 level: 4
      year overall survival at 100% vs 36% (p = .011), respectively. A specific gene
      signature including 57 genes was correlated to VEGF121 expression level and was
      analyzed using a discovery process in 1,842 GSE datasets of public microarray
      studies. This gene signature was significantly expressed in other cancer datasets
      and was associated with immune response. In conclusion, low VEGF121 expression
      level was significantly associated with a good prognosis in relapsed/refractory
      ABC-like DLBCL, and with a well-conserved gene-expression profiling signature
      related to immune response. These findings pave the way for rationalization of
      drugs targeting immune response in refractory/relapsed ABC-like DLBCL.

PMID- 29207606
TI  - Combination therapy with an OX40L fusion protein and a vaccine targeting the
      transcription factor twist inhibits metastasis in a murine model of breast
      cancer.
AB  - OX40 is a costimulatory receptor that potentiates proliferation, survival, memory
      formation, and effector function of CD4+ and CD8+ T-cells, while overcoming the
      suppressive activity of regulatory T-cells (Tregs). Here, we explored the
      combination of an OX40L fusion protein (OX40L-FP) with a poxvirus-based cancer
      vaccine (MVA-Twist-TRICOM) to inhibit tumor metastasis in the 4T1 murine breast
      cancer model. Contrary to the single agent treatments, the combination therapy
      significantly decreased the number of metastatic colonies per lung and prolonged
      survival. Depletion studies demonstrated that these effects were mediated by both
      CD4+ and CD8+ T-cells. The combination therapy a) increased the total number of T
      cells in the CD4+Foxp3- population and the CD4+ central and effector memory
      subsets within the lung, spleen, and draining lymph node, b) enhanced
      infiltration of CD4+ T-cells into metastatic areas of the lung, and (c) increased
      the number of functional CD8+ T-cells that produced IFNgamma and TNFalpha. The
      combination therapy also promoted the development of KLRG1-CD127+ memory
      precursor CD8+ T-cells, while reducing those with a KLRG1+ terminally
      differentiated phenotype. Moreover, the combination of OX40L-FP and vaccine
      induced greater CD4+ and CD8+ Twist-specific responses. In addition, Tregs
      isolated from mice receiving the combination were also less immunosuppressive in
      ex-vivo proliferation assays than those from the OX40L-FP and MVA-Twist-TRICOM
      monotherapy groups. Such results provide the rationale to combine co-stimulatory
      agonists with cancer vaccines for the treatment of tumor metastasis.

PMID- 29207607
TI  - Cyclin A2 regulates homologous recombination DNA repair and sensitivity to DNA
      damaging agents and poly(ADP-ribose) polymerase (PARP) inhibitors in human breast
      cancer cells.
AB  - Defects in homologous recombination (HR) repair are found in breast cancers.
      Intriguingly, breast cancers with defective HR show increased sensitivity to DNA
      crosslinking agents and poly(ADP-ribose) polymerase (PARP) inhibitors. As such,
      genes that can affect HR functions have been of high interest in studies aiming
      to develop biomarkers for predicting response to treatment with these agents.
      Cyclin A2 is a key component of the core cell cycle machinery. However, whether
      cyclin A2 dysfunctions could cause HR defect and mediate sensitivity to DNA
      damaging agents remain unclear. Here we show that loss of cyclin A2 causes high
      rates of double-strand breaks (DSB) in MCF-7 and MDA-MB-231 cells. The increased
      DSB was due to defective HR-mediated repair of the breaks, resulting from reduced
      MRE11 and RAD51 proteins. Cyclin A2 mediates MRE11 abundance through its MRE11
      mRNA binding property and RAD51 abundance through inhibition of proteasome
      degradation of RAD51. Moreover, cyclin A2 depletion hypersensitized the cells to
      DNA damaging agents, such as cisplatin and melphalan. Our results demonstrate
      novel roles for cyclin A2 in regulating HR repair and determining sensitivity to
      DNA cross linkers and PARP inhibitors in breast cancer cells.

PMID- 29207608
TI  - GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing
      allogeneic hematopoietic stem cell transplantation: a multicenter study.
AB  - Busulfan (BU) dose adjustment following therapeutic drug monitoring contributes
      to better outcome of hematopoietic stem cell transplantation (HSCT). Further
      improvement could be achieved through genotype-guided BU dose adjustments. To
      investigate this aspect, polymorphism within glutathione S transferase genes were
      assessed. Particularly, promoter haplotypes of the glutathione S transferase A1
      (GSTA1) were evaluated in vitro, with reporter gene assays and clinically, in a
      pediatric multi-center study (N =138) through association with BU
      pharmacokinetics (PK) and clinical outcomes. Promoter activity significantly
      differed between the GSTA1 haplotypes (p<0.001) supporting their importance in
      capturing PK variability. Four GSTA1 diplotype groups that significantly
      correlated with clearance (p=0.009) were distinguished. Diplotypes underlying
      fast and slow metabolizing capacity showed higher and lower BU clearance
      (ml/min/kg), respectively. GSTA1 diplotypes with slow metabolizing capacity were
      associated with higher incidence of sinusoidal obstruction syndrome, acute graft
      versus host disease and combined treatment-related toxicity (p<0.0005). Among
      other GST genes investigated, GSTP1 313GG correlated with acute graft versus host
      disease grade 1-4 (p=0.01) and GSTM1 non-null genotype was associated with
      hemorrhagic cystitis (p=0.003). This study further strengthens the hypothesis
      that GST diplotypes/genotypes could be incorporated into already existing
      population pharmacokinetic models for improving first BU dose prediction and HSCT
      outcomes. (No Clinicaltrials.gov identifier: NCT01257854. Registered 8 December
      2010, retrospectively registered).

PMID- 29207609
TI  - Reciprocal regulation of DGCR5 and miR-320a affects the cellular malignant
      phenotype and 5-FU response in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal
      malignancies. Long non-coding microRNAs (lncRNAs) are a newly discovered type of
      regulatory molecule with both diagnostic and prognostic value, but the role of
      lncRNA in PDAC has not been well investigated until now. Here, we present
      evidence that shows that the lncRNA DGCR5 is significantly reduced in PDAC
      tissues as well as in PDAC cell lines and that the downregulation of DGCR5
      predicts poor prognosis. Ectopic expression of DGCR5 inhibits the proliferation
      and migration, and promotes 5-FU resistances of PDAC cells. Further experiments
      demonstrated that DGCR5 and miR-320a regulate each other in a reciprocal manner
      and that DGCR5 reverses the inhibition of PDCD4 by miR-320a, which is involved in
      the regulation of the PDAC cell phenotype and response to 5-FU. Our findings
      provide novel information about the functions of lncRNAs in PDAC, some of which
      might be beneficial to the precise diagnosis, prognosis and individualized
      therapy of patients with PDAC in the future.

PMID- 29207611
TI  - The positivity of G-protein-coupled receptor-30 (GPR 30), an alternative estrogen
      receptor is not different between type 1 and type 2 endometrial cancer.
AB  - It is well-known that the clinical outcomes are different between type 1
      (estrogen dependent) and type 2 (estrogen independent) endometrial cancer.
      Studies have suggested that the estrogen receptor (ER) is positively correlated
      with endometrial cancer survival, however we previously reported that there is no
      difference in the positivity of ER as well as sex hormone levels between subtypes
      of cancer. G-protein-coupled receptor-30 (GPR 30), an alternative estrogen
      receptor has been suggested to be negatively correlated with clinical outcomes of
      endometrial cancer. In this study we investigated whether the positivity of GPR30
      is different between subtypes of cancer. The immunostaining of GPR30 and ER was
      examined and analysed in 128 cases taking into account menopausal status.
      Overall, 105 (82%) cases were GPR30 positive and 118 (92%) cases were ER
      positive. The positivity of GPR30 in type 1 endometrial cancer (83%) was not
      statistically different to type 2 endometrial cancer (78%). In addition,
      intensity of immunostaining of GPR30 in type 1 endometrial cancer was also not
      different to type 2 endometrial cancer quantified by semi-quantitative analysis
      (p = 0.268). Menopausal status was not associated with the positivity of GPR30 in
      both type 1 and type 2 endometrial cancer. Furthermore, the positivity and
      intensity of immunostaining of GPR30 were not correlated with the positivity and
      intensity of immunostaining of ER in endometrial cancer (p = 0.689). Our data
      further confirm that type 2 endometrial cancer may not be completely estrogen
      independent, and suggest that type 1 and type 2 endometrial cancer may have
      similar pathogenesis.

PMID- 29207612
TI  - The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced
      by andrographolide.
AB  - High concentrations of arsenic trioxide (As2O3) are used to treat acute
      promyelocytic leukemia and solid tumors, with negative side effects to normal
      cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer,
      anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the
      effects of combined andrographolide with As2O3 against hepatocellular carcinoma
      (HCC). We found that by increasing apoptosis, andrographolide synergistically
      enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo.
      Furthermore, results from our microarray assays and experiments with mouse
      xenografts showed that EphB4 was downregulated by the combination of As2O3 plus
      andrographolide. These findings suggest that the combination of andrographolide
      and As2O3 could yield therapeutic benefits in the treatment of HCC.

PMID- 29207610
TI  - Integration of microRNAome, proteomics and metabolomics to analyze arsenic
      induced malignant cell transformation.
AB  - Long-term exposure to arsenic has been linked to tumorigenesis in different
      organs and tissues, such as skin; however, the detailed mechanism remains
      unclear. In this present study, we integrated "omics" including microRNAome,
      proteomics and metabolomics to investigate the potential molecular mechanisms.
      Compared with non-malignant human keratinocytes (HaCaT), twenty-six miRNAs were
      significantly altered in arsenic-induced transformed cells. Among these miRNAs,
      the differential expression of six miRNAs was confirmed using Q-RT-PCR,
      representing potential oxidative stress genes. Two-dimensional gel
      electrophoresis (2D-PAGE) and mass spectrometry (MS) were performed to identify
      the differential expression of proteins in arsenic-induced transformed cells, and
      twelve proteins were significantly changed. Several proteins were associated with
      oxidative stress and carcinogenesis including heat shock protein beta-1 (HSPB1),
      peroxiredoxin-2 (PRDX2). Using ultra-performance liquid chromatography and Q-TOF
      mass spectrometry (UPLC/Q-TOF MS), 68 metabolites including glutathione, fumaric
      acid, citric acid, phenylalanine, and tyrosine, related to redox metabolism,
      glutathione metabolism, citrate cycle, met cycle, phenylalanine and tyrosine
      metabolism were identified and quantified. Taken together, these results
      indicated that arsenic-induced transformed cells exhibit alterations in miRNA,
      protein and metabolite profiles providing novel insights into arsenic-induced
      cell malignant transformation and identifying early potential biomarkers for
      cutaneous squamous cell carcinoma induced by arsenic.

PMID- 29207613
TI  - Changes in renal function indices in cirrhotic chronic hepatitis C patients
      treated with sofosbuvir-containing regimens.
AB  - This study aimed to explore changes in hepatic and renal function indices in
      chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs).
      Forty-three CHC patients treated with sofosbuvir (SOF)-containing regimens were
      enrolled. At the end of treatment, the estimated glomerular filtration rate
      (eGFR) level was significantly decreased and the serum creatinine (Scr) and uric
      acid (UA) levels were significantly increased compared with baseline levels
      (eGFR: 86.7 +/- 20.4 vs 80.5 +/- 21.3, P01 = 0.005; Scr: 83.9 +/- 19.1 vs 89.6 +/
      21.1, P01 < 0.001; UA: 323.7+/- 86.2 vs 358.5 +/- 93.2, P01 < 0.001); no
      significant improvements were observed at 24 w post-treatment (eGFR: 86.7 +/-
      20.4 vs 81.4 +/- 18.6, P02 = 0.013; Scr: 83.6 +/- 17.9 vs 87.9 +/- 18.3, P02 =
      0.014; UA: 320.8 +/- 76.3 vs 349.3 +/- 91.0, P02 = 0.004). When the patients were
      grouped by liver conditions, non-cirrhotic patients and cirrhotic patients had
      decreased eGFR levels and increased Scr levels at the end of treatment; at 24 w
      post-treatment, the eGFR and Scr levels were significantly improved in non
      cirrhotic patients (88.4 +/- 21.7 vs 83.8 +/- 18.5, P02 = 0.142; 84.4 +/- 20.4 vs
      87.0 +/- 16.9, P02 = 0.088), while no obvious improvements were observed in
      cirrhotic patients (84.3 +/- 18.7 vs 78.1 +/- 18.6, P02 = 0.002; 83.2 +/- 17.7 vs
      89.2 +/- 20.6, P02 = 0.006). Clinical physicians should closely monitor renal
      function in patients treated with SOF-containing regimens, especially in
      cirrhotic patients.

PMID- 29207614
TI  - Danshen improves survival of patients with advanced lung cancer and targeting the
      relationship between macrophages and lung cancer cells.
AB  - In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely
      used in the treatment of numerous cancers. However, its clinical effort and
      mechanism in the treatment of advanced lung cancer are unclear. In our study, the
      in vivo protective effort of danshen in patients with advanced lung cancer were
      validated using data from the National Health Insurance Research Database in
      Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive
      compound in danshen, exerts anticancer effects through many pathways. First, 10
      MUM DT substantially inhibited the migration ability of lung cancer cells in both
      macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10
      MUM DT repressed the phosphorylation of signal transducer and activator of
      transcription 3 (STAT3), the protein expression of S-phase kinase associated
      protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine
      (C-C motif) ligand 2 (CCL2). In addition, 10 MUM DT suppressed the macrophage
      recruitment ability of lung cancer cells by reducing CCL2 secretion from both
      macrophages and lung cancer cells. Third, 20 MUM DT induced apoptosis in lung
      cancer cells. Furthermore, DT treatment significantly inhibited the final tumor
      volume in a xenograft nude mouse model. In conclusion, danshen exerts protective
      efforts in patients with advanced lung cancer. These effects can be attributed to
      DT-mediated interruption of the cross talk between lung cancer cells and
      macrophages and blocking of lung cancer cell proliferation.

PMID- 29207615
TI  - PIK3CA mutations are associated with increased tumor aggressiveness and Akt
      activation in gastric cancer.
AB  - PIK3CA mutations are frequent in gastric cancer. However, their pathological and
      clinical implications are still unclear. We analyzed the clinicopathological
      characteristics according to the PIK3CA mutation status of patients with stage IB
      IV disease who underwent gastrectomy between May 2003 and Dec. 2005 (cohort 1; n
      = 302) and of those with stage IV disease who received gastrectomy between Jul.
      2006 and Dec. 2012 (cohort 2; n = 120). PIK3CA mutations were detected in 40
      patients (13.2%) in cohort 1. In these patients, PIK3CA-mutant tumors were more
      frequently located in the upper third of the stomach (p = 0.021) and
      significantly showed poorly differentiated histology (p = 0.018) and increased
      lymphatic (p = 0.015), vascular (p = 0.005), and perineural invasion (p = 0.026).
      In addition, these tumors showed significantly increased lymphocyte and
      neutrophil infiltration in cancer stroma (p < 0.001), Epstein-Barr virus
      positivity (p < 0.001), and microsatellite instability (p = 0.015). Cytoplasmic
      Akt expression was significantly increased in these tumors (p = 0.001). In cohort
      2, PIK3CA mutations were identified in 15 patients (12.5%). PIK3CA-mutant tumors
      showed significantly increased vascular invasion (p = 0.019) and microsatellite
      instability (p = 0.041). In addition, cytoplasmic Akt expression was also
      significantly increased (p = 0.018). However, in both cohorts, PIK3CA mutations
      were not associated with the prognosis of patients. In conclusion, PIK3CA
      mutations were associated with increased tumor aggressiveness, especially in
      locoregional disease, and Akt activation in gastric cancer. Our data suggest that
      PIK3CA-mutated gastric cancer is a distinct disease entity, which might need a
      different therapeutic approach.

PMID- 29207616
TI  - PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D
      glucose.
AB  - Cancer metabolism has emerged as an increasingly attractive target for
      interfering with tumor growth. Small molecule activators of pyruvate kinase
      isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on
      established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in
      increased glucose consumption, providing the rationale for combining PKM2
      activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination
      treatment resulted in reduced viability of a range of cell lines in standard cell
      culture conditions at concentrations of drugs that had no effect when used alone.
      This effect was replicated in vivo on established subcutaneous tumors. We further
      demonstrated the ability to detect acute metabolic differences in combination
      treatment using hyperpolarized magnetic resonance spectroscopy (MRS). Combination
      treated tumors displayed a higher pyruvate to lactate 13C-label exchange 2 hr
      post-treatment. This ability to assess the effect of drugs non-invasively may
      accelerate the implementation and clinical translation of drugs that target
      cancer metabolism.

PMID- 29207617
TI  - Phenotypic and clinical characterization of low density neutrophils in patients
      with advanced lung adenocarcinoma.
AB  - Purpose: An immunosuppressive subgroup of neutrophils, low density neutrophils
      (LDNs) was reported to be closely related to several diseases. This study was
      designed to explore the association between LDNs and advanced lung
      adenocarcinoma, as well as potential mechanisms. Results: The expression levels
      of surface CD molecules on LDNs were different from high density neutrophils
      (HDNs), consistent with previous studies. The ratio of LDNs/HDNs, rather than the
      percentage of LDNs in peripheral blood mononuclear cells (PBMCs), was
      significantly higher in lung adenocarcinoma patients than healthy controls. It
      was also observed that the ratio decreased when patients received anti-cancer
      treatments, and increased when disease relapsed. Patients harboring positive
      epidermal growth factor receptor (EGFR) mutation had significantly higher ratios.
      Both the ratio and the percentage showed positive correlation with CD8+ T cells.
      Although significantly increased TGF-beta was detected in lung adenocarcinoma
      patients, relationship between TGF-beta and LDNs was not obvious. Materials and
      Methods: LDNs and HDNs levels of peripheral blood from 52 lung adenocarcinoma
      patients and 13 healthy controls were determined by flow cytometry. Lymphocytes
      and cytokines were also detected. Conclusions: Two kinds of neutrophils with
      different phenotypes were identified in lung adenocarcinoma patients. Besides, we
      found the existence of high ratio of LDNs/HDNs in these patients, which is
      related to disease prognosis, EGFR mutation and bad immune status.

PMID- 29207618
TI  - Neuroprotective effect of a novel gastrodin derivative against ischemic brain
      injury: involvement of peroxiredoxin and TLR4 signaling inhibition.
AB  - The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling
      appears to be a potential therapeutic strategy for neuroinflammatory injury after
      acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for
      the treatment of cerebral ischemia, accompanied by regulation of the autoimmune
      inflammatory response. The present study investigated the neuroprotective effects
      of Gas and its derivative, Gas-D, with a focus on the potential mechanism
      associated with inflammatory Prx-Toll-like receptor 4 (TLR4) signaling. Gas-D
      significantly inhibited Prx1-, Prx2-, and Prx4-induced inflammatory responses in
      RAW264.7 macrophages and H2O2-mediated oxidative injury in SH-SY5Y nerve cells.
      In rats, intraperitoneal Gas-D administration 10 h after reperfusion following 2
      h middle cerebral artery occlusion (MCAO) ameliorated neurological deficits,
      brain infarction, and neuropathological alterations, including neuron loss,
      astrocyte and microglia/macrophage activation, T-lymphocyte invasion, and lipid
      peroxidation. Delayed Gas-D treatment significantly inhibited postischemic
      Prx1/2/4 expression and spillage, TLR4 signaling activation, and inflammatory
      mediator production. In contrast, Gas had no significant effects in either cell
      model or in MCAO rats under the same conditions. These results indicate that Gas
      D may be a drug candidate with an extended therapeutic time window that blocks
      inflammatory responses and attenuates the expression and secretome of
      inflammatory Prxs in acute ischemic stroke.

PMID- 29207619
TI  - Antitumor activity of gemcitabine against high-grade meningioma in vitro and in
      vivo.
AB  - Currently, there is no established therapeutic option for high-grade meningioma
      recurring after surgery and radiotherapy, and few chemotherapeutic agents are in
      development for the treatment of high-grade meningioma. Here in this study, we
      screened a panel of chemotherapeutic agents for their possible antitumor activity
      in high-grade meningioma and discovered that high-grade meningioma cells show a
      preferential sensitivity to antimetabolites, in particular, to gemcitabine. In
      vitro, gemcitabine inhibited the growth of high-grade meningioma cells
      effectively by inducing S-phase arrest and apoptotic cell death. In vivo,
      systemic gemcitabine chemotherapy suppressed not only tumor initiation but also
      inhibited the growth and achieved a long-term control of established tumors in
      xenograft models of high-grade meningioma. Histological analysis indicated that
      systemic gemcitabine blocks cell cycle progression and promotes apoptotic cell
      death in tumor cells in vivo. Together, our data demonstrate that gemcitabine
      exerts potent antitumor activity against high-grade meningioma through cytostatic
      and cytotoxic mechanisms. We therefore propose gemcitabine is a promising
      chemotherapeutic agent that warrants further investigation as a treatment option
      for high-grade meningioma.

PMID- 29207620
TI  - TXNDC5 is a cervical tumor susceptibility gene that stimulates cell migration,
      vasculogenic mimicry and angiogenesis by down-regulating SERPINF1 and TRAF1
      expression.
AB  - TXNDC5 (thioredoxin domain-containing protein 5) catalyzes disulfide bond
      formation, isomerization and reduction. Studies have reported that TXNDC5
      expression is increased in some tumor tissues and that its increased expression
      can predict a poor prognosis. However, the tumorigenic mechanism has not been
      well characterized. In this study, we detected a significant association between
      the rs408014 and rs7771314 SNPs at the TXNDC5 locus and cervical carcinoma using
      the Taqman genotyping method. We also detected a significantly increased
      expression of TXNDC5 in cervical tumor tissues using immunohistochemistry and
      Western blot analysis. Additionally, inhibition of TXNDC5 expression using siRNA
      prevented tube-like structure formation, an experimental indicator of
      vasculogenic mimicry and metastasis, in HeLa cervical tumor cells. Inhibiting
      TXNDC5 expression simultaneously led to the increased expression of SERPINF1
      (serpin peptidase inhibitor, clade F) and TRAF1 (TNF receptor-associated factor
      1), which have been reported to inhibit angiogenesis and metastasis as well as
      induce apoptosis. This finding was confirmed in Caski and C-33A cervical tumor
      cell lines. The ability to form tube-like structures was rescued in HeLa cells
      simultaneously treated with anti-TXNDC5, SERPINF1 and TRAF1 siRNAs. Furthermore,
      the inhibition of TXNDC5 expression significantly attenuated endothelial tube
      formation, a marker of angiogenesis, in human umbilical vein endothelial cells.
      The present study suggests that TXNDC5 is a susceptibility gene in cervical
      cancer, and high expression of this gene contributes to abnormal angiogenesis,
      vasculogenic mimicry and metastasis by down-regulating SERPINF1 and TRAF1
      expression.

PMID- 29207621
TI  - Genetic variation of lncRNA GAS5 contributes to the development of lung cancer.
AB  - Lung cancer remains the leading cause of cancer-related deaths throughout the
      world. In spite of great effort for the research of carcinogenesis, the molecular
      mechanisms of lung cancer remain unclear. In current study, we investigated the
      possible association between susceptibility of lung cancer and GAS5 rs145204276,
      which showed contradictory roles in carcinogenesis of colorectal cancer and
      hepatocellular carcinoma. We found that the del allele was significantly
      associated with 21% decreased risk of lung cancer (OR=0.79; 95% CI=0.66-0.93; P
      value = 0.006). Compared with the genotype ins/ins, both the genotype ins/del
      (OR=0.78; 95% CI=0.62-0.99) and del/del (OR=0.59;95% CI=0.39-0.89) showed
      decreased susceptibility of lung cancer. Real-time PCR analysis found that the
      expression levels of lncRNA GAS5 in lung cancer tissues were significantly lower
      than those in the corresponding normal tissues (P<0.01). Also the relative GAS5
      expression level in samples with del/del genotype was significantly higher than
      that in samples with ins/del and ins/ins genotype (P<0.01). Taken together, our
      findings provided strong evidence for the hypothesis that GAS5 rs145204276 were
      significantly associated with the susceptibility of lung cancer, and GAS5
      functions as a tumor suppressor in carcinogenesis of lung cancer.

PMID- 29207622
TI  - The performance of 11C-Methionine PET in the differential diagnosis of glioma
      recurrence.
AB  - Despite the advancement of neuroimaging techniques, it often remains a diagnostic
      challenge to distinguish recurrent glioma from lesions representing treatment
      effect. Preliminary reports suggest that 11C-methionine Positron emission
      tomography (PET) can assist in diagnosing true glioma recurrence. We present here
      a meta-analysis to assess the accuracy of 11C-methionine PET in identifying
      recurrent glioma in patients who had undergone prior therapy. A comprehensive
      search of the PubMed, Embase and Chinese Biomedical (CBM) databases yielded 23
      eligible articles comprising 29 studies listed prior to November 20, 2016,
      representing 891 patients. In this report, we assess the methodological quality
      of each article individually and perform a meta-analysis to obtain the summary
      diagnostic accuracy of 11C-methionine PET in correctly identifying recurrent
      glioma. The pooled sensitivity and specificity are 0.88 (95% CI: 0.85, 0.91) and
      0.85 (95% CI: 0.80, 0.89), respectively, with an area under the curve (AUC) for
      the summary receiver-operating characteristic curve (SROC) of 0.9352. We conclude
      that 11C-methionine PET has excellent diagnostic performance for differentiating
      glioma recurrence from treatment effect.

PMID- 29207623
TI  - Isoxazole compound ML327 blocks MYC expression and tumor formation in
      neuroblastoma.
AB  - Neuroblastomas are the most common extracranial solid tumors in children and
      arise from the embryonic neural crest. MYCN-amplification is a feature of ~30% of
      neuroblastoma tumors and portends a poor prognosis. Neural crest precursors
      undergo epithelial-to-mesenchymal transition (EMT) to gain migratory potential
      and populate the sympathoadrenal axis. Neuroblastomas are posited to arise due to
      a blockade of neural crest differentiation. We have recently reported effects of
      a novel MET inducing compound ML327 (N-(3-(2-hydroxynicotinamido) propyl)-5
      phenylisoxazole-3-carboxamide) in colon cancer cells. Herein, we hypothesized
      that forced epithelial differentiation using ML327 would promote neuroblastoma
      differentiation. In this study, we demonstrate that ML327 in neuroblastoma cells
      induces a gene signature consistent with both epithelial and neuronal
      differentiation features with adaptation of an elongated phenotype. These
      features accompany induction of cell death and G1 cell cycle arrest with blockage
      of anchorage-independent growth and neurosphere formation. Furthermore,
      pretreatment with ML327 results in persistent defects in proliferative potential
      and tumor-initiating capacity, validating the pro-differentiating effects of our
      compound. Intriguingly, we have identified destabilization of MYC signaling as an
      early and consistent feature of ML327 treatment that is observed in both MYCN
      amplified and MYCN-single copy neuroblastoma cell lines. Moreover, ML327 blocked
      MYCN mRNA levels and tumor progression in established MYCN-amplified xenografts.
      As such, ML327 may have potential efficacy, alone or in conjunction with existing
      therapeutic strategies against neuroblastoma. Future identification of the
      specific intracellular target of ML327 may inform future drug discovery efforts
      and enhance our understanding of MYC regulation.

PMID- 29207624
TI  - Autophagy suppression potentiates the anti-glioblastoma effect of asparaginase in
      vitro and in vivo.
AB  - Asparaginase has been reported to be effective in the treatment of various
      leukemia and several malignant solid cancers. However, the anti-tumor effect of
      asparaginase is always restricted due to complicated mechanisms. Herein, we
      investigated the mechanisms of how glioblastoma resisted asparaginase treatment
      and reported a novel approach to enhance the anti-glioblastoma effect of
      asparaginase. We found that asparaginase could induce growth inhibition and
      caspase-dependent apoptosis in U87MG/U251MG glioblastoma cells. Meanwhile,
      autophagy was activated as indicated by autophagosomes formation and upregulated
      expression of LC3-II. Importantly, abolishing autophagy using chloroquine (CQ)
      and LY294002 enhanced the cytotoxicity and apoptosis induced by asparaginase in
      U87MG/U251MG cells. Further study proved that Akt/mTOR and Erk signaling pathways
      participated in autophagy induction, while reactive oxygen species (ROS) served
      as an intracellular regulator for both cytotoxicity and autophagy in asparaginase
      treated U87MG/U251MG cells. Moreover, combination treatment with autophagy
      inhibitor CQ significantly enhanced anti-glioblastoma efficacy of asparaginase in
      U87MG cell xenograft model. Taken together, our results demonstrated that
      inhibition of autophagy potentiated the anti-tumor effect of asparagine depletion
      on glioblastoma, indicating that targeting autophagy and asparagine could be a
      potential approach for glioblastoma treatment.

PMID- 29207625
TI  - Stanniocalcin2 acts as an anorectic factor through activation of STAT3 pathway.
AB  - The regulation of food intake and body weight has been hotly investigated. In the
      present study, we show that stanniocalcin2 (STC2), a cytokine ubiquitously
      expressed and especially upregulated in many types of human cancers, has a
      regulatory role in food intake and weight loss. Systemic treatment of C57BL/6
      mice with recombinant STC2 protein resulted in decreased food intake and body
      weight, whereas energy expenditure was not affected. Similarly, STC2 treatment
      also induced anorexia in hyperphagic leptin-deficient mice, leading to a
      significant reduction in body weight and improvement of blood glucose levels.
      Furthermore, intracerebroventricular administration of STC2 to mice led to an
      acute decrease in food intake, which was mediated, at least in part, by
      activation of STAT3 pathway. Taken together, our results revealed the importance
      of STC2 in the regulation of feeding behavior as well as body weight.

PMID- 29207626
TI  - Perioperative outcomes of robotic surgery for the treatment of lung cancer
      compared to a conventional video-assisted thoracoscopic surgery (VATS) technique.
AB  - Aim: To conduct a meta-analysis to determine the relative merits between robotic
      video-assisted thoracoscopic surgery (R-VATS) and conventional video-assisted
      thoracoscopic surgery (VATS) for lung cancer. Results: Fifteen studies matched
      the selection criterion, which reported 8827 subjects, of whom 1704 underwent R
      VATS and 7123 underwent VATS. Compared the perioperative outcomes with VATS,
      reports of R-VATS indicated unfavorable outcomes considering the operative time
      (SMD = 0.48, 95% CI 0.15 to 0.81). Meanwhile, the number of dissected lymph nodes
      (SMD = 0.12, 95% CI -0.27 to 0.51) and hospital stay following surgery (SMD = 
      0.1; 95% CI -0.27 to 0.07), conversion (RR = 0.68; 95% CI 0.42 to 1.11),
      morbidity (RR = 0.99, 95% CI 0.92 to 1.07) and mortality (RR = 0.33, 95% CI 0.1
      to 1.09) were similar for both procedures. Materials and Methods: A literature
      search was performed to identify comparative studies reporting perioperative
      outcomes for R-VATS and VATS for lung cancer. Pooled risk ratio (RR) and
      standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were
      calculated using either the fixed effects model or the random effects model.
      Conclusions: There is no difference in terms of perioperative outcomes between R
      VATS and VATS except for the operative time which is significantly high for R
      VATS. Further studies are required to confirm these results.

PMID- 29207627
TI  - Orellanine specifically targets renal clear cell carcinoma.
AB  - Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney,
      accounts for approximately 85% of kidney cancers and causes over 140,000 annual
      deaths worldwide. In the last decade, several new therapies have been identified
      for treatment of metastatic RCC. Although these therapies increase survival time
      compared to standard care, none of them has curative properties. The nephrotoxin
      orellanine specifically targets proximal tubular epithelial cells, leaving other
      organs unaffected. We therefore hypothesized that the selective toxicity of
      orellanine extends to clear cell RCC (ccRCC) cells since they emanate from
      proximal tubular cells. Orellanine would thus target both primary and metastatic
      ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell
      death in proximal tubular cells and in all ccRCC cells tested, both primary and
      cell lines, with no toxicity detected in control cells. The toxic action of
      orellanine involve decreased protein synthesis, disrupted cell metabolism and
      induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief
      orellanine treatment eliminated more than 90% of viable tumor mass compared to
      control rats. This identifies orellanine as a potential treatment concept for
      ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC.

PMID- 29207628
TI  - Sigma-1 and Sigma-2 receptor ligands induce apoptosis and autophagy but have
      opposite effect on cell proliferation in uveal melanoma.
AB  - Uveal melanoma is the most common primary intraocular tumor in adults, with about
      1200-1500 new cases occurring per year in the United States. Metastasis is a
      frequent occurrence in uveal melanoma, and outcomes are poor once distant spread
      occurs and no clinically significant chemotherapeutic protocol is so far
      available. The aim of the present study was to test the effect of various sigma1
      and sigma2 receptor ligands as a possible pharmacological strategy for this rare
      tumor. Human uveal melanoma cells (92.1) were treated with various concentrations
      of different sigma2 ligands (haloperidol and haloperidol metabolite II) and
      sigma1 ligand ((+)-pentazocine) at various concentrations (1, 10 and 25 MUM) and
      time points (0, 4 h, 8 h, 24 h and 48 h). Cell proliferation and migration were
      evaluated respectively by continuous cell monitoring by xCELLigence analysis,
      clonogenic assay and wound healing. Apoptosis and autophagy were also measured by
      cytofluorimetric and microscopy analysis. Our results showed that sigma2 receptor
      ligands significantly reduced cell proliferation whereas (+)-pentazocine
      exhibited opposite results. All tested ligands showed significant decrease in
      cell migration. Interestingly, both sigma1 and sigma2 receptor ligands showed
      significant increase of autophagy and apoptosis at all concentrations. Taken all
      together these results suggest that sigma receptors mediates opposite biological
      effects but they also share common pharmacological effect on apoptosis and
      autophagy in uveal melanoma. In conclusion, these data provide the first evidence
      that sigma receptors may represent a "druggable" target to develop new
      chemotherapic agent for uveal melanoma.

PMID- 29207629
TI  - Genetic deletion of Rnd3 in neural stem cells promotes proliferation via
      upregulation of Notch signaling.
AB  - Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics
      through the Rho kinase-dependent signaling pathway. We previously demonstrated
      that mice with genetic deletion of Rnd3 developed a markedly larger brain
      compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice
      developed an enlarged subventricular zone, and we identify a novel role for Rnd3
      as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in
      vivo and in vitro, resulted in increased levels of Notch intracellular domain
      protein. This led to enhanced Notch signaling and promotion of aberrant neural
      stem cell growth, thereby resulting in a larger subventricular zone and a
      markedly larger brain. Inhibition of Notch activity abrogated this aberrant
      neural stem cell growth.

PMID- 29207630
TI  - Shp2 regulates migratory behavior and response to EGFR-TKIs through ERK1/2
      pathway activation in non-small cell lung cancer cells.
AB  - In the clinical treatment of lung cancer, therapy failure is mainly caused by
      cancer metastasis and drug resistance. Here, we investigated whether the tyrosine
      phosphatase Shp2 is involved in the development of metastasis and drug resistance
      in non-small cell lung cancer (NSCLC). Shp2 was overexpressed in a subset of lung
      cancer tissues, and Shp2 knockdown in lung cancer cells inhibited cell
      proliferation and migration, downregulated c-Myc and fibronectin expression, and
      upregulated E-cadherin expression. In H1975 cells, which carry double mutations
      (L858R + T790M) in epidermal growth factor receptor (EGFR) that confers
      resistance toward the tyrosine kinase inhibitor gefitinib, Shp2 knockdown
      increased cellular sensitivity to gefitinib; conversely, in H292 cells, which
      express wild-type EGFR and are sensitive to gefitinib, Shp2 overexpression
      increased cellular resistance to gefitinib. Moreover, by overexpressing Shp2 or
      using U0126, a small-molecule inhibitor of extracellular signal-regulated kinase
      1/2 (ERK1/2), we demonstrated that Shp2 inhibited E-cadherin expression and
      enhanced the expression of fibronectin and c-Myc through activation of the ERK1/2
      pathway. Our findings reveal that Shp2 is overexpressed in clinical samples of
      NSCLC and that Shp2 knockdown reduces the proliferation and migration of lung
      cancer cells, and further suggest that co-inhibition of EGFR and Shp2 is an
      effective approach for overcoming EGFR T790M mutation acquired resistance to EGFR
      tyrosine kinase inhibitors (TKIs). Thus, we propose that Shp2 could serve as a
      new biomarker in the treatment of NSCLC.

PMID- 29207631
TI  - Tetrahydrocurcumin induces mesenchymal-epithelial transition and suppresses
      angiogenesis by targeting HIF-1alpha and autophagy in human osteosarcoma.
AB  - Human osteosarcoma is considered a malignant tumor with poor prognosis that
      readily metastasizes. Tetrahydrocurcumin (THC) has been reported to have anti
      tumor activity in numerous tumors. In addition, hypoxia-inducible factor-1alpha
      (HIF-1alpha) has been demonstrated to be associated with tumor metastasis by
      regulating epithelial-mesenchymal transition (EMT). However, the role of THC in
      osteosarcoma remains uncertain. Therefore, this study aimed to elucidate the
      potential mechanisms. We found that THC significantly reduced the growth of
      osteosarcoma cells and suppressed migration and invasion, as tested in a nude
      mouse lung metastasis model. Additionally, the mesenchymal-epithelial transition
      (MET) process was facilitated by THC. Mechanistically, our study showed that HIF
      1alpha had a pivotal role in the anti-metastatic effect of THC. Importantly, HIF
      1alpha expression was downregulated by THC by inhibiting Akt/mTOR and p38 MAPK
      pathways. Moreover, THC exhibited a remarkable inhibitory effect on HIF-1alpha
      expression and angiogenesis under hypoxic conditions. Furthermore, THC activated
      autophagy and induced MET and suppressed angiogenesis in a HIF-1alpha-related
      manner. Taken together, our findings suggest that THC suppresses metastasis and
      invasion and this may be associated with HIF-1alpha and autophagy, which would
      potentially provide therapeutic strategies for human osteosarcoma.

PMID- 29207632
TI  - Addition of 5-fluorouracil to first-line induction chemotherapy with docetaxel
      and cisplatin before concurrent chemoradiotherapy does not improve survival in
      locoregionally advanced nasopharyngeal carcinoma.
AB  - Although a multicenter, randomized study indicated that induction chemotherapy
      (IC) with docetaxel/cisplatin/fluorouracil (TPF) before concurrent
      chemoradiotherapy (CCRT) improves survival outcomes, it remains unclear whether
      TPF is the best IC regimen for treating locoregionally advanced nasopharyngeal
      carcinoma (NPC). Our aim was to compare the efficacy and toxicities of TPF vs.
      docetaxel/cisplatin (TP) IC followed by CCRT in patients with locoregionally
      advanced NPC. One hundred thirty-two patients with locoregionally advanced NPC
      received 21-day cycles of IC with either TPF or TP. Both were followed by
      intensity-modulated radiotherapy concurrent with the cisplatin treatment every 3
      weeks. Three-year rates of locoregional relapse-free survival, distant metastasis
      free survival, progression-free survival, and overall survival were respectively
      96.4%, 87.7%, 86.0%, and 94.7% for patients in the TPF arm patients and 90.3%,
      91.9%, 85.2%, and 92.0% for patients in the TP arm. There were no differences in
      survival between the two arms. Multivariate analysis revealed the IC regimen was
      not an independent prognostic factor for any survival outcome. However, patients
      in the TP arm experienced fewer grade 3/4 toxicities. In sum, IC with docetaxel
      and cisplatin is associated with similar efficacy and less toxicity than the TPF
      regimen. Addition of fluorouracil to docetaxel plus cisplatin IC is therefore not
      recommended for patients with locoregionally advanced NPC.

PMID- 29207634
TI  - Treatment plan comparison between Tri-Co-60 magnetic-resonance image-guided
      radiation therapy and volumetric modulated arc therapy for prostate cancer.
AB  - To investigate the plan quality of tri-Co-60 intensity-modulated radiation
      therapy (IMRT) with magnetic-resonance image-guided radiation therapy compared
      with volumetric-modulated arc therapy (VMAT) for prostate cancer. Twenty patients
      with intermediate-risk prostate cancer, who received radical VMAT were selected.
      Additional tri-Co-60 IMRT plans were generated for each patient. Both primary and
      boost plans were generated with tri-Co-60 IMRT and VMAT techniques. The
      prescription doses of the primary and boost plans were 50.4 Gy and 30.6 Gy,
      respectively. The primary and boost planning target volumes (PTVs) of the tri-Co
      60 IMRT were generated with 3 mm margins from the primary clinical target volume
      (CTV, prostate + seminal vesicle) and a boost CTV (prostate), respectively. VMAT
      had a primary planning target volume (primary CTV + 1 cm or 2 cm margins) and a
      boost PTV (boost CTV + 0.7 cm margins), respectively. For both tri-Co-60 IMRT and
      VMAT, all the primary and boost plans were generated that 95% of the target
      volumes would be covered by the 100% of the prescription doses. Sum plans were
      generated by summation of primary and boost plans. In sum plans, the average
      values of V70 Gy of the bladder of tri-Co-60 IMRT vs. VMAT were 4.0% +/- 3.1% vs.
      10.9% +/- 6.7%, (p < 0.001). Average values of V70 Gy of the rectum of tri-Co-60
      IMRT vs. VMAT were 5.2% +/- 1.8% vs. 19.1% +/- 4.0% (p < 0.001). The doses of tri
      Co-60 IMRT delivered to the bladder and rectum were smaller than those of VMAT
      while maintaining identical target coverage in both plans.

PMID- 29207633
TI  - CaMKII is involved in subcellular Ca2+ redistribution-induced endoplasmic
      reticulum stress leading to apoptosis in primary cultures of rat proximal tubular
      cells exposed to lead.
AB  - Lead (Pb) is a known nephrotoxic element. Recently we have proved that
      subcellular Ca2+ redistribution is involved in Pb-induced apoptosis in primary
      cultures of rat proximal tubular (rPT) cells, but the underlying mechanism
      remains to be elucidated. Firstly, data showed that Pb triggers endoplasmic
      reticulum (ER) stress response in rPT cells, as evidenced by the elevations of ER
      stress markers. Moreover, pharmacological modulation of Ca2+ mobilization in ER
      and cytoplasm with three chemicals (2-APB or TG or BAPTA-AM) can effectively
      increase or decrease the protein expression of ER stress markers in Pb-exposed
      rPT cells, demonstrating that Pb-induced ER stress is Ca2+-dependent. We found
      that Pb stimulates phosphorylation of calcium/calmodulin-dependent protein kinase
      II (CaMKII) to activate its activity. Meanwhile, inhibition of CaMKII with KN93
      or KN62 attenuated Pb-activated caspase-12 and CCAAT/enhancer-binding protein
      homologous protein (CHOP) in rPT cells, demonstrating that CaMKII activation
      promoted ER stress in rPT cells. Likewise, Pb-induced apoptosis can be
      effectively inhibited by CaMKII inhibitor KN93 or KN62. Furthermore, co-treatment
      with KN93 or KN62 significantly reversed Pb-induced ER Ca2+ release and
      concomitant intracellular Ca2+ overload in rPT cells. In summary, these results
      expound the mechanisms involving in ER stress, Ca2+ dyshomeostasis and activated
      CaMKII, which all contribute to Pb-induced apoptosis. CaMKII acts as a critical
      mediator of ER stress and associated apoptosis via regulating intracellular Ca2+
      mobilization from ER to cytoplasm.

PMID- 29207635
TI  - SOCS2 overexpression alleviates diabetic nephropathy in rats by inhibiting the
      TLR4/NF-kappaB pathway.
AB  - Suppressor of cytokine signaling 2 (SOCS2) was reported to be involved in the
      development of Diabetic Nephropathy (DN). However, its underlying mechanism
      remains undefined. Western blot was carried out to determine the expressions of
      SOCS2, Toll-like receptors 4 (TLR4) and nuclear factor kappa B (NF-kappaB)
      pathway-related proteins in DN patients, streptozotocin (STZ)-induced DN rats and
      high glucose (HG)-stimulated podocytes. The effects of SOCS2 overexpression on
      renal injury, the inflammatory cytokines production, renal pathological changes,
      apoptosis and the TLR4/NF-kappaB pathway in DN rats or HG-stimulated podocytes
      were investigated. TLR4 antagonist TAK-242 and NF-kappaB inhibitor PDTC were used
      to confirm the functional mechanism of SOCS2 overexpression in HG-stimulated
      podocytes. SOCS2 was down-regulated, while TLR4 and NF-kappaB were up-regulated
      in renal tissues of DN patients and DN rats. Ad-SOCS2 infection alleviated STZ
      induced renal injury and pathological changes and inhibited STZ-induced IL-6, IL
      1beta and MCP-1 generation and activation of the TLR4/NF-kappaB pathway in DN
      rats. SOCS2 overexpression attenuated apoptosis, suppressed the inflammatory
      cytokines expression, and inactivated the TLR4/NF-kappaB pathway in HG-stimulated
      podocytes. Suppression of the TLR4/NF-kappaB pathway enhanced the inhibitory
      effect of SOCS2 overexpression on apoptosis and inflammatory cytokines
      expressions in HG-stimulated podocytes. SOCS2 overexpression alleviated the
      development of DN by inhibiting the TLR4/NF-kappaB pathway, contributing to
      developing new therapeutic strategies against DN.

PMID- 29207636
TI  - Characterization of urinary extracellular vesicle proteins in muscle-invasive
      bladder cancer.
AB  - The mechanisms of bladder cancer progression are unknown, and new treatments and
      biomarkers are needed. Patient urinary extracellular vesicles (EVs) derive in
      part from bladder cancer cells and contain a specific protein cargo which may
      provide information about the disease. We conducted a proteomics study comparing
      EVs from the muscle-invasive bladder cancer (MIBC) cell line TCCSUP to EVs from
      normal urothelial line SVHUC. GO term analysis showed that TCCSUP EVs are
      enriched in proteins associated with the cell membrane, extracellular matrix, and
      inflammation and angiogenesis signaling pathways. Proteins characteristic of
      cancer EVs were further screened at the mRNA level in bladder cancer cell lines.
      In Western blots, three of six proteins examined showed greater than fifteenfold
      enrichment in patient urinary EVs compared to healthy volunteers (n = 6).
      Finally, we performed immunohistochemical staining of bladder tissue microarrays
      for three proteins of interest. One of them, transaldolase (TALDO1), is a nearly
      ubiquitous enzyme and normally thought to reside in the cytoplasm. To our
      surprise, nuclei were stained for transaldolase in 94% of MIBC tissue samples (n
      = 51). While cytoplasmic transaldolase was found in 89-90% of both normal
      urothelium (n = 79) and non-muscle-invasive samples (n = 71), the rate falls to
      39% in MIBC samples (P < 0.001), and negative cytoplasmic staining was correlated
      with worse cancer-specific survival in MIBC patients (P = 0.008). The
      differential EV proteomics strategy reported here successfully identified a
      number of proteins associated with bladder cancer and points the way to future
      investigation.

PMID- 29207637
TI  - Wheat germ agglutinin-induced paraptosis-like cell death and protective autophagy
      is mediated by autophagy-linked FYVE inhibition.
AB  - Wheat germ agglutinin (WGA) is a lectin that specifically binds cell surface
      glycoproteins and disrupts nuclear pore complex function through its interaction
      with POM121. Our data indicate WGA induces paraptosis-like cell death without
      caspase activation. We observed the main features of paraptosis, including
      cytoplasmic vacuolation, endoplasmic reticulum dilation and increased ER stress,
      and the unfolded protein response in WGA-treated cervical carcinoma cells.
      Conversion of microtubule-associated protein I light chain 3 (LC3-I) into LC3-II
      and punctuate formation suggestive of autophagy were observed in WGA-treated
      cells. WGA-induced autophagy antagonized paraptosis in HeLa and CaSKi cells,
      which expressed autophagy-linked FYVE (Alfy) protein, but not in SiHa cells that
      did not express Alfy. Alfy knockdown in HeLa cells induced paraptosis-like cell
      death. These data indicate that WGA-induced cell death occurs through paraptosis
      and that autophagy may exert a protective effect. WGA treatment and Alfy
      inhibition could be an effective therapeutic strategy for apoptosis-resistant
      cervical cancer cells.

PMID- 29207638
TI  - Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress
      Ca2+-mitochondria dependent pathway.
AB  - Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer
      related diseases. In this study, we aimed to investigate the anticancer effect of
      Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried
      roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms.
      We found that JB suppressed the cell viability and colony formation of CRC cells,
      HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC
      cells, which was further confirmed by the increased expression of cleaved
      caspase3 and cleaved-PARP. iTRAQ-based quantitative proteomics was performed to
      identify JB-regulated proteins in CRC cells. Gene Ontology (GO) analysis revealed
      that these JB-regulated proteins were mainly involved in ER stress response,
      which was evidenced by the expression of ER stress marker proteins, HSP90, Bip
      and PDI. Moreover, we found that JB provoked the generation of reactive oxygen
      species (ROS), and that inhibition of the ROS generation with N-acetyl L-cysteine
      could reverse the JB-induced apoptosis. Confocal microscopy and flow cytometry
      showed that JB treatment enhanced intracellular and mitochondrial Ca2+ level and
      JC-1 assay revealed a loss of mitochondrial membrane potential in CRC after JB
      treatment. The mitochondrial Ca2+ uptake and depolarization can be blocked by
      Ruthenium Red (RuRed), an inhibitor of mitochondrial Ca2+ uniporter. Taken
      together, we demonstrated that JB exerts its anticancer effect by ER stress-Ca2+
      mitochondria signaling, suggesting the promising chemotherapeutic potential of JB
      for the treatment of CRC.

PMID- 29207639
TI  - Comparative efficacy of different chemotherapies for non-Hodgkin lymphoma: a
      network-meta analysis.
AB  - This network meta-analysis (NMA) was conducted to integrate different
      chemotherapeutic regimens for non-Hodgkin lymphoma (NHL) patients. Overall
      survival (OS) and complete remission (CR) were considered as main outcome
      indicators to evaluate the efficacy of NHL chemotherapies. OS and CR data were
      extracted from included studies and represented by hazard ratio and odds ratio
      separately. Network structure and forest plots were further included to visually
      present the relative efficacy among different regimens. A total of 14 qualified
      publications with 4,167 patients were included. In OS results, no significant
      difference was observed from the 1-year OS. For 2-year, 3-year and 5-year OS,
      patients treated by CNOP exhibited the least favorable results. Moreover,
      significant advantages of R-CHOP treatment over CHOP and VMP were recognized in
      view of 3-year OS. In respect of CR, R-HDS presented significantly better
      outcomes than CNOP and VMP, and no significant difference was identified when
      compared to CHOP in forest plot. ProMACE-CytaBOM and R-HDS possessed the
      compelling cumulative ranking probability in OS or CR, indicating their
      competitive performance in NHL treatment while R-CHOP and I-CHOP yielded
      desirable in terms of long-term survival and short-term survival, respectively.
      To conclude, ProMACE-CytaBOM, I-CHOP, R-HDS and R-CHOP were recommended to go
      through further evaluation to confirm their superiority in NHL treatment. CNOP
      and VMP were discouraged after comprehensively analyzing OS and CR from NMA
      results.

PMID- 29207640
TI  - Accurate quantification of 5-Methylcytosine, 5-Hydroxymethylcytosine, 5
      Formylcytosine, and 5-Carboxylcytosine in genomic DNA from breast cancer by
      chemical derivatization coupled with ultra performance liquid chromatography-
      electrospray quadrupole time of flight mass spectrometry analysis.
AB  - The DNA demethylation pathway has been discovered to play a significant role in
      DNA epigenetics. This pathway removes the methyl group from cytosine, which is
      involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC)
      by ten-eleven translocation (TET) proteins. Then, 5-hmC can be iteratively
      oxidized to generate 5-formylcytosine (5-foC) and 5-carboxylcytosine (5-caC).
      However, 5-hmC, 5-foC, and 5-caC are hardly detected due to their low content. In
      this study, we have developed a LC-HRMS method coupled with derivatization to
      accurately and simultaneously quantify 5-mC levels, along with its oxidation
      products in genomic DNA. Derivatization was carried out using 4-dimethylamino
      benzoic anhydride, which has been shown to improve separation and enhance the
      detection sensitivity. Finally, we successfully applied this method towards the
      quantification of 5-mC, 5-hmC, 5-foC, and 5-caC in genomic DNA isolated from both
      human breast cancer tissue and tumor-adjacent normal tissue. We show that 5-foC
      and 5-caC are increased in tumor tissue. In addition, the levels of 5-mC, 5-hmC,
      5-foC, and 5-caC measured in tumor tissue versus tumor-adjacent tissue were found
      to be distinct among different classifications. This suggests that cytosine
      modifiers could be used as potential biomarkers for determining the stage of
      development of breast cancer, as well as prognosis.

PMID- 29207641
TI  - A small molecule, (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol
      suppresses tumor growth via inhibition of IkappaB kinase beta in colorectal
      cancer in vivo and in vitro.
AB  - Here we report that a novel synthesized compound (E)-2-methoxy-4-(3-(4
      methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) which exhibits better stability, drug
      likeness and anti-cancer effect than (E)-2,4-bis(p-hydroxyphenyl)-2-butenal
      (BHPB) that we previously reported. Of all newly synthesized BHPB analogues, MMPP
      showed the most significant inhibitory effect on colon cancer cell growth. Thus,
      we evaluated the anti-cancer effects and possible mechanisms of MMPP in vitro and
      in vivo. MMPP treatment (0-15 MUg/mL) induced apoptotic cell death and enhanced
      the expression of cleaved caspase-3 and cleaved caspase-8 in a concentration
      dependent manner. Notably, the expression of death receptor (DR)5 and DR6 was
      significantly increased by MMPP treatment. Moreover, DR5 siRNA or DR6 siRNA
      transfection partially abolished MMPP-induced cell growth inhibition. Pull down
      assay and docking experiment showed that MMPP bound directly to IkappaB kinase
      beta (IKKbeta). It was noteworthy that IKKbeta mutant (C99S) partially abolished
      MMPP-induced cell growth inhibition and enhanced expression of DR5 and DR6. In
      addition, MMPP enhanced TRAIL-induced apoptosis, cell growth inhibition and
      expression of DRs. In xenograft mice model, MMPP (2.5-5 mg/kg) suppressed tumor
      growth in a dose dependent manner. Immunohistochemistry analysis showed that the
      expression levels of DR5 and DR6 and active caspase-3 were increased while the
      expression levels of PCNA and p-IKKbeta were decreased in a dose dependent
      manner. Thus, MMPP may be a promising anti-cancer agent in colon cancer
      treatment.

PMID- 29207642
TI  - Crosstalk in competing endogenous RNA network reveals the complex molecular
      mechanism underlying lung cancer.
AB  - We investigated the transcriptional mechanism underlying lung cancer development.
      RNA sequencing analysis was performed on blood samples from lung cancer cases and
      healthy controls. Differentially expressed microRNAs (miRNAs), circular RNAs
      (circRNAs), mRNAs (genes), and long non-coding RNAs (lncRNA) were identified,
      followed by pathway enrichment analysis. Based on miRNA target interactions, a
      competing endogenous network was established and significant nodes were screened.
      Differentially expressed transcriptional factors were retrieved from the TRRUST
      database and the transcriptional factor regulatory network was constructed. The
      expression of 59 miRNAs, 18,306 genes,232 lncRNAs, and 292 circRNAs were greatly
      altered in patients with lung cancer. miRNAs were closely associated with cancer
      related pathways, such as pathways in cancer, colorectal cancer, and
      transcriptional misregulation in cancer. Two novel pathways, olfactory
      transduction and neuroactive ligand-receptor interactions, were significantly
      enriched by differentially expressed genes. The competing endogenous RNA network
      revealed 5 hub miRNAs. Hsa-miR-582-3p and hsa-miR-582-5p were greatly enriched in
      the Wnt signaling pathway. Hsa-miR-665 was closely related with the MAPK
      signaling pathway. Hsa-miR-582-3p and hsa-miR-582-5p were also present in the TF
      regulatory network. Transcriptional factors of WT1 (wilms tumor 1) and ETV1 (ETS
      variant 1) were regulated by hsa-miR-657 and hsa-miR-582-5p, respectively, and
      controlled androgen receptor gene expression. miR-582-5p, miRNA-582-3p, and miR
      657 may play critical regulatory roles in lung tumor development. Our work may
      explore new mechanism of lung cancer and aid the development of novel therapy.

PMID- 29207643
TI  - LncRNA-UCA1 enhances MMP-13 expression by inhibiting miR-204-5p in human
      chondrocytes.
AB  - Osteoarthritis (OA) is a common degenerative disease characterized by
      degeneration of articular cartilage. Increasing studies showed that long
      noncoding RNAs (lncRNAs) play important roles in the cartilage damage. However,
      little is known about the role of UCA1 in the osteoarthritis. The expression
      level of UCA1 was upregulated in the OA cartilage. Overexpression of UCA1
      suppressed the miR-204-5p expression in the chondrocytes. The expression of miR
      204-5p was downregulated in the OA cartilage. Moreover, the expression of miR-204
      5p was negatively correlated with the UCA1 expression in the OA cartilage.
      Elevated expression of UCA1 promoted the chondrocytes cell proliferation and
      overexpression of miR-204-5p suppressed chondrocytes cell proliferation. In
      addition, overexpression of UCA1 decreased the expression of the type II collagen
      and type IV collagen expression in the chondrocytes. Elevated expression of miR
      204-5p promoted the type II collagen and type IV collagen expression in the
      chondrocytes. We idetified MMP-13 was a direct target gene of miR-204-5p in the
      chondrocytes. Overexpression of UCA1 enhanced the MMP-13 expression in the
      chondrocytes. Elevated expression of UCA1 regulated the chondrocytes cell
      proliferation and collagen expression through inhibiting the miR-204-5p
      expression.These results suggested that UCA1 played as an important regulator of
      survival and matrix synthesis of chondrocytes partly through suppressing the miR
      204-5p expression.

PMID- 29207644
TI  - Protection by simvastatin on hyperglycemia-induced endothelial dysfunction
      through inhibiting NLRP3 inflammasomes.
AB  - Recent studies have demonstrated that NLRP3 inflammasome complex acts as pivotal
      elements to initiate inflammatory responses and plays an important role in the
      dysfunction of cardiovascular complications. Meanwhile, simvastatin prevents
      vascular endothelial dysfunction from inflammasome invasion contributing to
      reduce cardiovascular risk. However, Whether or not the simvastatin improves
      vascular endothelial barrier function through inhibiting the activation of NLRP3
      inflammasome pathway remains unknown. Here, we explored the role and mechanisms
      of simvastatin in the activation of NLRP3 inflammasome which are involved in
      vascular endothelial hyperpermeability causing by the disruption of tight
      junction protein ZO-1 and adherens junction protein VE-Cadherin, an early
      initiation of cardiovascular complication. Our results found that high glucose
      significantly induced the formation and activation of NLRP3 inflammasome through
      NADPH oxidase-dependent reactive oxygen species (ROS) formation, associated with
      vascular endothelial hyperpermeability causing by ZO-1 and VE-Cadherin disruption
      in the rat aortic endothelial cells (RAECs). Simvastatin treatment remarkably
      abolished vascular endothelial hyperpermeability and enhanced the protein
      expression of ZO-1 and VE-Cadherin through NLRP3 inflammasome. Mechanistically,
      the inhibitory role of simvastatin endothelial hyperpermeability is attributed to
      the decreased release of cytoplasmic high mobility group box protein-1 (HMGB1)
      derived from endothelial NLRP3 inflammasome activation. We further confirm the
      protective role of simvastatin on vascular leakage in the heart of diabetic rats
      injected with Evans blue dye, which was associated with HMGB1 release in the
      serum. Collectively, the mechanism of simvastatin treatment alleviating vascular
      endothelial permeability dysfunction may be through inhibiting the NLRP3
      inflammasome-dependent HMGB1 release in RAECs.

PMID- 29207645
TI  - Nitidine chloride acts as an apoptosis inducer in human oral cancer cells and a
      nude mouse xenograft model via inhibition of STAT3.
AB  - Nitidine chloride (NC) is a natural alkaloid compound derived from the plant
      Zanthoxylum nitidum and is known for its therapeutic anticancer potential. In
      this study, we investigated the effects of NC on growth and signaling pathways in
      human oral cancer cell lines and a tumor xenograft model. The apoptotic effects
      and related molecular targets of NC on human oral cancer were investigated using
      trypan blue exclusion assay, DAPI staining, Live/Dead assay, Western blotting,
      Immunohistochemistry/Immunofluorescence and a nude mouse tumor xenograft. NC
      decreased cell viability in both HSC3 and HSC4 cell lines; further analysis
      demonstrated that cell viability was reduced via apoptosis. STAT3 was hyper
      phosphorylated in human oral squamous cell carcinoma (OSCC) compared with normal
      oral mucosa (NOM) and dephosphorylation of STAT3 by the potent STAT3 inhibitor,
      cryptotanshinone or NC decreased cell viability and induced apoptosis. NC also
      suppressed cell viability and induced apoptosis accompanied by dephosphorylating
      STAT3 in four other oral cancer cell lines. In a tumor xenograft model bearing
      HSC3 cell tumors, NC suppressed tumor growth and induced apoptosis by regulating
      STAT3 signaling without liver or kidney toxicity. Our findings suggest that NC is
      a promising chemotherapeutic candidate against human oral cancer.

PMID- 29207646
TI  - TGFbeta1 induces hypertrophic change and expression of angiogenic factors in
      human chondrocytes.
AB  - The transforming growth factor beta1 (TGFbeta1) plays an important role in
      cartilage development. However, whether TGFbeta1 stimulates chondrocyte
      proliferation and cartilage regeneration in osteoarthritis (OA) remains elusive,
      especially in the context of different treatment and tissue environments. In the
      present study, we investigated the role of TGFbeta1 in human chondrocyte culture
      in vitro, focusing on the morphological change of chondrocytes and the expression
      of angiogenic factors upon TGFbeta1 stimulation. We found increased expression of
      biomarkers indicating chondrocyte hypertrophy and the chondrocytes aggregated to
      form networks when they were treated with TGFbeta1. DNA microarray analysis
      revealed significantly increased expression of genes related to blood vessel
      formation in TGFbeta1 treatment group compared to control group. Matrigel assay
      further demonstrated that chondrocytes had the potential to form network-like
      structure. These results suggested that TGFbeta1 induces the hypertrophic change
      of chondrocytes culture in vitro and induce expression of angiogenic biomarkers.
      Therefore, application of TGFbeta1 for chondrocyte culture in practice should be
      considered prudentially and targeting TGFbeta1 or relevant receptors to block the
      signaling pathway might be a strategy to prevent or alleviate progression of
      osteoarthritis.

PMID- 29207647
TI  - Response to transarterial chemoembolization may serve as selection criteria for
      hepatocellular carcinoma liver transplantation.
AB  - Aims: This study sought to extend the inclusion criteria for hepatocellular
      carcinoma (HCC) liver transplantation (LT), particularly addressing the safety
      and effectiveness of pre-LT transarterial chemoembolization (TACE). Materials and
      Methods: Our study included 115 patients with HCC who underwent LT after TACE.
      The response measured after each TACE session was based on the mRECIST criteria:
      complete response (CR), partial response (PR), stable disease (SD) or progressive
      disease (PD). We defined CR and PR patients as responders (64 cases) and SD and
      PD patients as non-responders (51 cases). Results: The majority of responders
      could be identified after the first or second TACE sessions (57 cases, 89.1%).
      Overall survival rates at 1, 3 and 5 years were 95.3%, 89.1% and 75.0%,
      respectively, in the responder group, and these rates were much higher than those
      in the non-responder group (86.3%, 66.7% and 54.9%, P=0.016). In addition, the
      tumor-free survival rate in the responder group was also higher than in the non
      responder group (P=0.009). In the responder group, a statistically improved long
      term outcome was observed in patients whose HCC did not satisfy the Milan
      criteria (P<0.05). Univariate and multivariate Cox analyses showed that achieving
      CR or PR was the best predictor of survival and tumor-free survival following
      TACE. Conclusion: The response to TACE, particularly following the first two
      sessions, primarily and robustly predicted overall and tumor-free survival in HCC
      patients, particularly those whose HCC did not satisfy the Milan criteria.

PMID- 29207648
TI  - CASC15 gene polymorphisms reduce neuroblastoma risk in Chinese children.
AB  - In this case-control study, we analyzed the association between three single
      nucleotide polymorphisms (SNPs) in the CASC15 gene (rs6939340 A>G, rs4712653 T>C,
      and rs9295536 C>A) and neuroblastoma susceptibility in the Guangdong and Henan
      populations of China. We genotyped and analyzed 118 cases and 281 control
      subjects from Henan province and combined them with previously published data
      from the Guangdong population. In the Henan population, only the rs6939340 G>A
      variant homozygote AA was associated with decreased neuroblastoma risk [AA vs.
      GG: adjusted odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23-0.98;
      P=0.045]. All three polymorphisms, individually and in combination, were
      associated with decreased neuroblastoma susceptibility in the Guangdong
      population. Moreover, subjects carrying 1-3 of these protective genotypes had
      lower neuroblastoma susceptibility than non-carriers (adjusted OR=0.65, 95%
      CI=0.51-0.84, P=0.0007). These results show that all three genetic variants of
      CASC15 identified in a genome-wide association study (GWAS) decrease
      neuroblastoma risk in two distinct Chinese populations.

PMID- 29207649
TI  - Sulodexide recovers endothelial function through reconstructing glycocalyx in the
      balloon-injury rat carotid artery model.
AB  - Disruption of endothelial cell function is a principle event in cardiovascular
      disease. Accordingly, therapies have mostly focused on repairing the endothelium,
      but little attention has been paid to the reconstruction of glycocalyx, which
      covers the endothelium and protects the function of endothelial cells. Sulodexide
      has a similar glycosaminoglycan structure to glycocalyx, so it is assumed to be
      effective in remodeling the glycocalyx following damage. We assessed the effect
      of sulodexide on glycocalyx remodeling and endothelial function in the balloon
      injury rat carotid artery model. Electron micrographs showed that sulodexide
      (2mg/kg, administered by intraperitoneal injection for seven days after injury)
      could reconstruct the endothelial glycocalyx and recover the clear
      cytoarchitecture. With regard to endothelial function, sulodexide increased
      endothelial nitric oxide synthase level, attenuated endothelial hyperplasia, and
      inhibited platelet aggregation that benefitted from glycocalyx reforming.
      Sulodexide decreased the glycocalyx damage related expression of CD31 and
      intercellular cell adhesion molecule-1 in endothelium, accompanying by the
      downregulation of leukocyte counts and C-reactive protein levels. The levels of
      the atherosclerosis-related factors, osteopontin and vascular cell adhesion
      molecule-1, which increased in activated endothelial cells lacking glycocalyx,
      were normalized by sulodexide. Along with the benefit of glycocalyx
      reconstruction, sulodexide reversed the dyslipidemia. Moreover, sulodexide
      prevented CD68-positive inflammatory cells infiltration into the vascular wall,
      presumably as a result of glycocalyx reconstruction. In summary, sulodexide
      treatment reconstructed glycocalyx which therefore preserved endothelial function
      and attenuated the expression of inflammatory factors, and decreased the blood
      coagulation and lipid metabolism, all of which are important for vascular
      healing.

PMID- 29207650
TI  - Upregulation of miR-181a impairs hepatic glucose and lipid homeostasis.
AB  - The contributions of altered post-transcriptional gene silencing to the
      development of metabolic disorders remain poorly understood thus far. The
      objective of this study was to evaluate the roles of miR-181a in the regulation
      of hepatic glucose and lipid metabolism. MiR-181a is abundantly expressed in the
      liver, and we found that blood and hepatic miR-181a levels were significantly
      increased in patients and dairy cows with non-alcoholic fatty liver disease, as
      well as in high-fat diet and ob/ob mice. We determined that sirtuin1 is a target
      of miR-181a. Moreover, we found that hepatic sirtuin1 and peroxisome proliferator
      activated receptor-gamma coactivator-1alpha expression levels are downregulated,
      and acetylated peroxisome proliferator-activated receptor-gamma coactivator
      1alpha expression levels are upregulated in patients and dairy cows with non
      alcoholic fatty liver disease, as well as in high-fat diet and ob/ob mice. MiR
      181a overexpression inhibits the sirtuin1-peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha pathway, reduces insulin sensitivity, and
      increases gluconeogenesis and lipid synthesis in dairy cow hepatocytes and HepG2
      cells. Conversely, silencing of miR-181a over-activates the sirtuin1-peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha pathway, increases
      insulin sensitivity and glycogen content, and decreases gluconeogenesis and lipid
      synthesis in hepatocytes, even under non-esterified fatty acids treatment
      conditions. Furthermore, miR-181a overexpression or sirtuin1 knockdown in mice
      increases lipid accumulation and decreases insulin sensitivity and glycogen
      content in the liver. Taken together, these findings indicate that increased
      hepatic miR-181a impairs glucose and lipid homeostasis by silencing sirtuin1 in
      non-alcoholic fatty liver disease.

PMID- 29207651
TI  - Matrix metalloproteinase-1 expression in breast carcinoma: a marker for
      unfavorable prognosis.
AB  - Matrix metalloproteinase-1 (MMP1) is a member of the matrix metalloproteinases
      family, and its aberrant expression is implicated in tumor invasion and
      metastasis. However, the relationship between MMP1 abnormal expression and
      clinical outcome in breast cancer patients remains to be elucidated. To address
      this issue, we conducted immunohistochemistry in breast cancer and adjacent
      normal tissues, and mined the transcriptional and survival data of MMP1 in breast
      cancer patients through Oncomine, Kaplan-Meier Plotter, bc-GenExMiner, COSMIC and
      cBioPortal databases. First, we found that both protein and mRNA levels of MMP1
      expression were significantly higher in breast cancer tissues. Second, high MMP1
      mRNA expression correlated with worse overall survival among grade II (HR = 1.75;
      p = 0.011), nodal-negative (HR = 2.00; p = 0.00028), ER-positive (HR = 1.61; p =
      0.00027) and HER2-negative (HR = 3.17; p = 0.029) patients with breast cancer by
      using Kaplan-Meier plotter database. Third, the overexpression of MMP1 was
      associated with unfavorable survival results including overall survival (HR =
      1.6; p = 1.6e-05), relapse free survival (HR = 1.78; p < 1e-16) and distant
      metastasis free survival (HR = 1.65; p = 5.3e-05) in patients with breast cancer.
      Taken together, the expression status of MMP1 is a significant prognostic
      indicator and a potential drug target for breast cancer.

PMID- 29207652
TI  - IQCA-TAVV: To explore the effect of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8
      on deep venous thrombosis.
AB  - Deep vein thrombosis (DVT) associates with considerable morbidity, functional
      disability and mortality. Due to the lack of suitable inhibitor the correlation
      of various factors in DVT onset remains unknown. In this context we analyzed the
      structure of anti-platelet aggregation agent, P-selectin down-regulator,
      GPIIb/IIIa down-regulator and anti-inflammatory agent, thereby designed N-(3S
      1,2,3,4-tetrahydroisoquinoline-3-carbonyl)- Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA
      TAVV) as an inhibitor of DVT to receive evaluations. The docking predicted that
      IQCA-TAVV can target P-selectin and GPIIb/IIIa. The UV showed that IQCA-TAVV can
      act on P-selectin and GPIIb/IIIa. ELISA indicated that IQCA-TAVV concentration
      dependently inhibited activated platelets to express P-selectin and GPIIb/IIIa,
      and the minimal effective concentration was 1 nM. IC50 of IQCA-TAVV against
      platelet aggregation induced by arachidonic acid, adenosine diphosphate and
      platelet activating factor fell within a range of 0.13 nM to 0.30 nM. In vivo
      IQCA-TAVV dose-dependently inhibited venous thrombosis and the minimal effective
      dose was 1 nmol/kg. On ear edema model the anti-inflammation activity of 10
      nmol/kg IQCA-TAVV equaled that of 1.1mmol/kg aspirin. The concentration of IL-2,
      IL-6 and IL-8 in the serum of the ear edema mice were also significantly
      decreased by 10 nmol/kg IQCA-TAVV. Even at 1 MUmol/kg of dose IQCA-TAVV still did
      not injure the kidney, the liver, and the nerves of healthy mice. Thereby IQCA
      TAVV depicts a relationship of three levels (inhibiting platelet activation,
      targeting externalized membrane receptor, decreasing serum inflammatory factor)
      for the down-regulation of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 in DVT.

PMID- 29207653
TI  - Melatonin enhances sorafenib actions in human hepatocarcinoma cells by inhibiting
      mTORC1/p70S6K/HIF-1alpha and hypoxia-mediated mitophagy.
AB  - The antiangiogenic effects of sustained sorafenib treatment in hepatocellular
      carcinoma (HCC) lead to the occurrence of hypoxia-mediated drug resistance
      resulting in low therapy efficiency and negative outcomes. Combined treatments
      with coadjuvant compounds to target the hypoxia-inducible factor-1alpha (HIF
      1alpha) represent a promising therapeutic approach through which sorafenib
      efficiency may be improved. Melatonin is a well-documented oncostatic agent
      against different cancer types. Here, we evaluated whether melatonin could
      enhance sorafenib cytotoxicity and overcome the hypoxia-mediated resistance
      mechanisms in HCC. The pharmacological melatonin concentration (2 mM) potentiated
      the oncostatic effects of sorafenib (5 MUM) on Hep3B cells even under hypoxia.
      Melatonin downregulated the HIF-1alpha protein synthesis through the inhibition
      of the mammalian target of rapamycin complex 1 (mTORC1)/ribosomal protein S6
      kinase beta-1 (p70S6K)/ribosomal protein S6 (RP-S6) pathway, although the indole
      enhanced Akt phosphorylation by the mTORC1/C2 negative feedback. Furthermore,
      melatonin and sorafenib coadministration reduced the HIF-1alpha-mitophagy targets
      expression, impaired autophagosome formation and subsequent mitochondria and
      lysosomes colocalization. Together, our results indicate that melatonin improves
      the Hep3B sensitivity to sorafenib, preventing HIF-1alpha synthesis to block the
      cytoprotective mitophagy induced by the hypoxic microenvironment, an important
      element of the multifactorial mechanisms responsible for the chemotherapy
      failure.

PMID- 29207654
TI  - Genetic variations in LIGHT are associated with susceptibility to ankylosing
      spondylitis in a Chinese Han population.
AB  - Ankylosing spondylitis (AS) is a common chronic autoimmune disease characterized
      by inflammation of axial skeleton and has strong genetic susceptibility. Single
      nucleotide polymorphisms (SNPs) have been found playing an important role in the
      development of AS. This study intends to explore whether the susceptibility to AS
      is associated with rs2171513 C>T, rs1077667 G>A in LIGHT (lymphotoxin, expressed
      on T lymphocytes) and rs12609318 A>G in B and T lymphocyte attenuator (BTLA) in a
      Chinese Han population. We studied a total of 497 AS patients and 387 healthy
      controls in the current research. Clinical characteristics were recorded when
      they were recruited. Single nucleotide polymorphisms (SNPs) were genotyped by
      polymerase chain reaction (PCR) and high-resolution melting methods (HRM).
      Statistically significant difference was found in both co-dominant model (GG vs.
      GA vs. AA) (p = 4.00E-06) and alleles (p = 4.59E-08) of rs1077667 between
      patients and controls. There was also a significant difference in alleles of
      rs2171513 (p = 0.037) between patients and controls. We found rs1077667 in LIGHT
      and rs2171513 in BTLA with susceptibility to AS, while 12609318 in LIGHT
      associate with susceptibility to AS. Our results showed that LIGHT might be
      involved in pathogenesis of AS.

PMID- 29207655
TI  - Egr-1 regulates RTA transcription through a cooperative involvement of
      transcriptional regulators.
AB  - Kaposi's sarcoma associated herpesvirus (KSHV) regulates the host cellular
      environment to establish life-long persistent infection by manipulating cellular
      signaling pathways, with approximately 1- 5% of cells undergoing lytic
      reactivation during the course of infection. Egr-1 (Early Growth Response Factor
      1) is one such cellular transcription factor, which gets phosphorylated during
      the lytic phase of viral life cycle to perpetrate its function. This study
      demonstrates the mechanism of how Egr-1 mediates transcription of the immediate
      early gene, RTA (Replication and transcription activator), which is the lytic
      switch gene of KSHV. Egr-1 depleted KSHV infected cells exhibited reduced
      expression of RTA. Also, an increase in Egr-1 phosphorylation led to a higher
      virion production, which was suppressed in the presence of p38 and Raf
      inhibitors. Reporter assays showed that coexpression of Egr-1 and CBP (CREB
      binding protein) enhances RTA promoter activity as compared to the expression of
      either Egr-1 or CBP alone. Binding of Egr-1 and CBP at RTA promoter was analyzed
      by chromatin immunoprecipitation assay (ChIP), which showed an enhanced
      accumulation during viral reactivation. Mutation in Egr-1 binding site of the RTA
      promoter eliminated Egr-1 response on promoter activation. Furthermore, de novo
      infection of THP-1 (monocytic) and HUVECs (endothelial) cells showed an
      upregulation of Egr-1 phosphorylation, whereas depletion of Egr-1 reduced the
      mRNA levels of RTA during primary infection. Together, these results demonstrate
      a cooperative role of Egr-1 and CBP in mediating RTA transcription, which
      significantly improves our understanding of the involvement of cellular factors
      controlling RTA transcription in KSHV pathogenesis.

PMID- 29207656
TI  - CCR6 is required for ligand-induced CatSper activation in human sperm.
AB  - CatSper channel has been considered the principal sperm Ca2+ channel responsible
      for the cytosolic Ca2+ elevation required for various sperm functions necessary
      for fertilization [1-4]. However, the mechanism underlying the activation of
      CatSper channel by various physiological ligands remain incompletely understood.
      We have recently demonstrated the expression of C-C chemokine receptor 6 (CCR6)
      in sperm and Ca2+ influx upon binding of human beta-defensin 1 (DEFB1) to CCR6,
      which is important for sperm motility [5]. In the present study, we have
      demonstrated that CCR6 receptor and CatSper channel are both required for the
      Ca2+ entry/current induced by physiological ligands DEFB1, chemokine (C-C motif)
      ligand 20 (CCL20) and progesterone in human sperm. CCR6 is co-localized and
      interacts with CatSper in human sperm. Ca2+ influx mediated by CCR6 and CatSper
      is required for essential sperm functions, including motility, hyperactivation
      and acrosome reaction, which are impaired in infertile sperm showing reduced
      levels of CCR6 and CatSper. The present finding suggests a critical role of CCR6
      receptor in mediating ligand-induced, CatSper-dependent Ca2+ influx required for
      various sperm functions and thus male fertility.

PMID- 29207657
TI  - Discovery of novel frizzled-7 inhibitors by targeting the receptor's
      transmembrane domain.
AB  - Frizzled (Fzd) proteins are seven transmembrane receptors that belong to a novel
      and separated family of G-protein-coupled receptors (GPCRs). The Fzd receptors
      can respond to Wnt proteins to activate the canonical beta-catenin pathway which
      is important for both initiation and progression of cancers. Disruption of the
      Wnt/beta-catenin signal thus represents an opportunity for rational cancer
      prevention and therapy. Of the 10 members of the Fzd family, Fzd7 is the most
      important member involved in cancer development and progression. In the present
      studies, we applied structure-based virtual screening targeting the transmembrane
      domain (TMD) of Fzd7 to select compounds that could potentially bind to the Fzd7
      TMD and block the Wnt/Fzd7 signaling and further evaluated them in biological
      assays. Six small molecule compounds were confirmed as Fzd7 inhibitors. The best
      hit, SRI37892, significantly blocked the Wnt/Fzd7 signaling with IC50 values in
      the sub-micromolar range and inhibited cancer cell proliferation with IC50 values
      around 2 MUM. Our results provide the first proof of concept of targeting Fzd-TMD
      for the development of Wnt/Fzd modulators. The identified small molecular Fzd7
      inhibitors can serve as a useful tool for studying the regulation mechanism(s) of
      Wnt/Fzd7 signaling as well as a starting point for the development of cancer
      therapeutic agents.

PMID- 29207658
TI  - Overexpression of RAD51B predicts a preferable prognosis for non-small cell lung
      cancer patients.
AB  - Lung cancer is the leading cause of cancer-related death. The majority of
      patients are diagnosed at an incurable advanced stage with poor prognosis. A
      recent study associated the methylation of homologous recombination genes with
      expression of immune checkpoints in lung squamous cell carcinoma. However, the
      correlation between them remains unclear. In our study, we propose that RAD51B, a
      repair gene in the homologous recombination process, which is noticed to be a key
      player in the maintenance of chromosome integrity and in sensing DNA damage, can
      act as an independent factor affecting the prognosis of non-small-cell lung
      cancer (NSCLC). Univariate analysis showed that overexpression of RAD51B is
      statistically significant correlated with better prognosis (P=0.013). Further,
      the multivariate Cox regression analysis showed that the morbidity of patients
      with high expression of RAD51B was decreased by 26% compared to those with low
      expression (HR=0.74, 95%CI: 0.59-0.93), especially for the patients with squamous
      cell carcinoma (HR=0.68, 95%CI: 0.51-0.90). In conclusion, RAD51B in mRNA level
      can be an important indicator to decide the prognosis of NSCLC and its
      overexpression predicts a preferable prognosis for NSCLC. Our results serve as a
      foundation for the investigation of the role of RAD51B in NSCLC, which may lead
      to potential therapeutic innovations.

PMID- 29207659
TI  - 2-(3, 4-dihydroxybenzylidene)malononitrile as a novel anti-melanogenic compound.
AB  - Tyrosinase is a key player in ultraviolet-induced melanogenesis. Because
      excessive melanin accumulation in the skin can induce hyperpigmentation, the
      development of tyrosinase inhibitors has attracted attention in cosmetic-related
      fields. However, side effects including toxicity and low selectivity have limited
      the use of many tyrosinase inhibitors in cosmetics. We synthesized 12 novel 2
      (substituted benzylidene)malononitrile derivatives and investigated their anti
      melanogenic activities. Of these 12 compounds, 2-(3, 4-dihydroxy
      benzylidene)malononitrile (BMN11) exhibited the strongest inhibitory activity
      against tyrosinase (IC50 = 17.05 MUM). In parallel with this, BMN11 treatment
      notably decreased alpha-melanocyte-stimulating hormone-induced melanin
      accumulation in B16F10, cells without toxicity and also decreased melanin
      accumulation in a human skin model. As a mechanism underlying the BMN11-mediated
      anti-melanogenic effect, docking simulation showed that BMN11 can directly bind
      to tyrosinase by forming two hydrogen bonds with GLY281 and ASN260 residues, and
      via three hydrophobic interactions with VAL283, PHE264, and ALA286 residues in
      the tyrosinase binding pocket, and this likely contributes to its inhibitory
      effect on tyrosinase. Consistently, Lineweaver-Burk and Cornish-Bowden plots
      showed that BMN11 is a competitive inhibitor of tyrosinase. We concluded that
      BMN11 may be a novel tyrosinase inhibitor that could be used in cosmetics.

PMID- 29207660
TI  - Genetic polymorphisms of ATG5 predict survival and recurrence in patients with
      early-stage esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is a deadly disease with high risk of
      tumor recurrence even among patients with an early pathologic stage of tumor. In
      the current study, we investigate the association between 20 SNPs of the ATG5
      gene and prognosis of patients with early-stage ESCC. A total of 305 patients
      diagnosed with early-stage ESCC were enrolled in the study and randomly assigned
      to a training set (n=93) or replication set (n=212). The genotypes of candidate
      SNPs (single nucleotide polymorphisms) within ATG5 were analyzed and correlated
      with the prognosis of ESCC patients. We repeatedly demonstrated that 3 SNPs in
      ATG5, rs1322178, rs3804329, and rs671116, were significantly correlated with the
      prognosis of patients with early-stage ESCC (HR[95 % CI]=2.01[1.19-3.40], p=0.009
      for ATG5: rs1322178; HR[95 % CI]=1.88 [1.08-3.26], p=0.025 for ATG5:rs3804329;
      HR[95 % CI]=1.73[1.24-2.42], p=0.001 for ATG5:rs671116, in combined group). Both
      rs1322178 and rs3804329 can predict early distant metastasis of patients.
      Furthermore, increased expression of ATG5 was observed in ESCC tumor tissue as
      compared to adjacent normal tissue. Moreover, higher levels of ATG5 expression in
      both normal and tumor tissues exhibited a trend to correlate with poor prognosis
      of patients. However, the expression of ATG5 did not correlate with these 3
      relevant prognostic SNPs. We concluded that hereditary genetic polymorphisms and
      gene expression of ATG5 can serve as prognostic predictors of patients with early
      stage ESCC.

PMID- 29207661
TI  - Immunization with recombinant rabies virus expressing Interleukin-18 exhibits
      enhanced immunogenicity and protection in mice.
AB  - Several studies have shown that interleukin-18 (IL-18) plays an important role in
      both innate and adaptive immune responses. In this study, we investigated the
      pathogenicity and immunogenicity of recombinant rabies virus expressing IL-18
      (rHEP-IL18). Experimental results showed that Institute of Cancer Research (ICR)
      mice that received a single intramuscular immunization with rHEP-IL18 elicited
      the highest titers of serum neutralizing antibodies and the strongest cell
      mediated immune responses to prevent the development of rabies disease, compared
      with immunization with the parent virus HEP-Flury. Mice inoculated with rHEP-IL18
      developed significantly higher IFN-gamma responses, increased percentages of CD4+
      and CD8+ T-lymphocytes compared to HEP-Flury. Flow cytometry results show that
      rHEP-IL18 recruited more activated T- and B-cells in lymph nodes or peripheral
      blood, which is beneficial for virus clearance in the early stages of infection.
      A higher percentage of mice immunized with rHEP-IL18 survived wild-type rabies
      virus (RABV) challenge, compared to HEP-Flury mice. Our results show that rHEP
      IL18 is promising as a novel vaccine for RABV prevention and control.

PMID- 29207662
TI  - Tumor-associated macrophages promote neuroblastoma via STAT3 phosphorylation and
      up-regulation of c-MYC.
AB  - Tumor-associated macrophages (TAMs) are strongly associated with poor survival in
      neuroblastomas that lack MYCN amplification. To study TAM action in
      neuroblastomas, we used a novel murine model of spontaneous neuroblastoma lacking
      MYCN amplification, and observed recruitment and polarization of TAMs, which in
      turn enhanced neuroblastoma proliferation and growth. In both murine and human
      neuroblastoma cells, we found that TAMs increased STAT3 activation in
      neuroblastoma cells and transcriptionally up-regulated the MYC oncogene. Analysis
      of human neuroblastoma tumor specimens revealed that MYC up-regulation correlates
      with markers of TAM infiltration. In an IL6ko neuroblastoma model, the absence of
      IL-6 protein had no effect on tumor development and prevented neither STAT3
      activation nor MYC up-regulation. In contrast, inhibition of JAK-STAT activation
      using AZD1480 or the clinically admissible inhibitor ruxolitinib significantly
      reduced TAM-mediated growth of neuroblastomas implanted subcutaneously in NOD
      scid gamma mice. Our results point to a unique mechanism in which TAMs promote
      tumor cells that lack amplification of an oncogene common to the malignancy by up
      regulating transcriptional expression of a distinct oncogene from the same gene
      family, and underscore the role of IL-6-independent activation of STAT3 in this
      mechanism. Amplification of MYCN or constitutive up-regulation of MYC protein is
      observed in approximately half of high-risk tumors; our findings indicate a novel
      role of TAMs as inducers of MYC expression in neuroblastomas lacking independent
      oncogene activation.

PMID- 29207663
TI  - MicroRNA-218 inhibits proliferation and invasion in ovarian cancer by targeting
      Runx2.
AB  - MicroRNA-218 (miR-218) has been implicated in the development and progression of
      multiple cancers. We investigated the role of miR-218 in ovarian cancer
      progression. We found that miR-218 expression levels were lower in ovarian cancer
      tissues and cell lines than in adjacent normal tissues or a normal ovarian cell
      line.miR-218 levels associated with International Federation of Gynecology and
      Obstetrics (FIGO) stage and lymph node metastasis. Exogenous expression of miR
      218 inhibited cell proliferation, colony formation, migration, and invasion in
      vitro and suppressed tumor growth in a tumor-bearing nude mouse model. Runt
      related transcription factor 2 (RUNX2) was identified as a direct functional
      target of miR-218, and its expression was inversely correlated with miR-218
      expression in ovarian cancer tissues. RUNX2 overexpression rescued the
      suppressive effect of miR-218 on ovarian cancer cell proliferation, colony
      formation, migration, and invasion. These findings highlight an important role
      played bymiR-218 in the regulation of cancer growth and metastasis, in part by
      repressing RUNX2, and revealed the potential of miR-218 as a new therapeutic
      target inovarian cancer.

PMID- 29207664
TI  - Shikonin protects against D-Galactosamine and lipopolysaccharide-induced acute
      hepatic injury by inhibiting TLR4 signaling pathway.
AB  - Shikonin, a naphthoquinone isolated from the root of medical herb Lithospermum
      erythrorhizon, has been reported to have anti-inflammatory effect. However, there
      is no related research for the treatment of shikonin on hepaic injury. The
      purpose of this study was to investigate the effects of shikonin on D
      Galactosamine and Lipopolysaccharide-induced hepatic injury in mice. Male BALB/c
      mice were pretreated with shikonin 1 h before LPS/D-GalN treatment. The
      pathological changes of hepatic injury were detected by H&E staining. The levels
      of TNF-alpha and IL-1beta in hepatic tissues were detected by ELISA. The levels
      of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also
      measured in this study. In addition, the expression of TLR4 and NF-kappaB were
      determined by western blot analysis. These results suggest that shikonin
      effectively prevents LPS/D-GalN-induced liver injury by inhibiting AST and ALT
      levels, as well as inflammatory cytokines TNF-alpha and IL-1beta production. The
      expression of TLR4 and NF-kappaB activation induced by LPS/D-GalN were also
      inhibited by treatment of shikonin. In vitro, shikonin significantly inhibited
      LPS-induced TNF-alpha and IL-1beta production, as well as TLR4 expression and NF
      kappaB activation. In conclusion, the results of the present study suggest that
      shikonin attenuates LPS/D-GalN-induced hepatic injury by inhibiting TLR4
      signaling pathway.

PMID- 29207665
TI  - miR-15b represses BACE1 expression in sporadic Alzheimer's disease.
AB  - Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is conceived as a
      potential target for therapies against Alzheimer disease (AD). MicroRNAs (miRNAs)
      are small non-coding RNAs that negatively regulate gene expression in a sequence
      specific manner. Although miRNAs have been increasingly recognized as important
      modulators in sporadic AD. In order to confirm whether miR-15b correlates with
      the BACE1 upregulation in sporadic AD, we firstly evaluated the expression of miR
      15b and BACE1 in sporadic AD brain tissues and analyzed the correlation of miR
      15b with BACE1. Then we determined the regulation of miR-15b in SH-SY5Y cells on
      the BACE1 expression. And finally we determined the targeting to 3' UTR of BACE1
      by miR-15b by a luciferase reporter. Downregulation of miR-15b alleviated Abeta
      induced viability inhibition and decreased apoptosis in SH-SY5Y cells. Our
      results demonstrated that miR-15b play an important role in the cellular AD
      phenotype and might be involved in the pathogenesis of AD.

PMID- 29207666
TI  - Integrative analysis to identify oncogenic gene expression changes associated
      with copy number variations of enhancer in ovarian cancer.
AB  - Enhancers are short regulatory regions (50-1500 bp) of DNA that control the
      tissue-specific activation of gene expression by long distance interaction with
      targeting gene regions. Recently, genome-wide identification of enhancers in
      diverse tissues and cell lines was achieved using high-throughput sequencing.
      Enhancers have been associated with malfunctions in cancer development resulting
      from point mutations in regulatory regions. However, the potential impact of copy
      number variations (CNVs) on enhancer regions is unknown. To learn more about the
      relationship between enhancers and cancer, we integrated the CNVs data on
      enhancers and explored their targeting gene expression pattern in high-grade
      ovarian cancer. Using human enhancer-gene interaction data with 13,691
      interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found
      that the 2,910 copy number gain events of enhancer are significantly correlated
      with the up-regulation of targeting genes. We further identified that a number of
      highly mutated super-enhancers, with concordant gene expression change on their
      targeting genes. We also identified 18 targeting genes by super-enhancers with
      prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B.
      We are the first to report that abundant copy number variations on enhancers
      could change the expression of their targeting genes which would be valuable for
      the design of enhancer-based cancer treatment strategy.

PMID- 29207667
TI  - Prevalence of and risk factors for cystic echinococcosis among herding families
      in five provinces in western China: a cross-sectional study.
AB  - Echinococcosis is a severe zoonosis that endangers the health of herdsmen in
      China's western provinces. This study aimed to examine the prevalence of this
      disease and identify potential factors associated with human echinococcosis among
      herding families. A cross-sectional study was conducted in five provinces in
      western China from May 1, 2016 to November 30, 2016, and 1500 herding families
      participated in the study. A total of 1211 completed questionnaires were
      analyzed. The prevalence of Cystic echinococcosis (CE) among surveyed herding
      families was 1.55%. The results of multivariate analysis revealed that the sheep
      immunization (OR=0.35, 95%CI 0.21-0.58), being concerned about family members
      echinococcosis (OR=0.49, 95%CI 0.28-0.84) were protective factors, while allowing
      dogs to roam free (OR=3.17, 95%CI 1.89-5.31), feeding dogs with viscera (OR=3.04,
      95%CI 1.83, 5.03), slaughter at home (OR=3.53, 95%CI 2.04-6.12), drinking non
      boiled water (OR=2.15, 95%CI 1.28-3.63), eating raw vegetables (OR=1.87, 95%CI
      1.13-3.10), not washing hands before meals (OR=3.08, 95%CI 1.68-5.65), and often
      seeing stray dogs (OR=2.60 95%CI 1.38-4.91) and wild animals (OR=1.92, 95%CI 1.17
      3.14) near habitations were more associated with increased risk of infection.
      Immunizing sheep, appropriately managing domestic and stray dogs, and improving
      living environments and behavioral factors may help to reduce the risk of human
      echinococcosis in western China.

PMID- 29207668
TI  - Genetic or pharmacologic inhibition of EGFR ameliorates sepsis-induced AKI.
AB  - Despite recent studies have demonstrated that the EGF receptor (EGFR) activation
      provided a renoprotective role during ischemic and folic acid-induced AKI, the
      role and regulation mechanism of EGFR in septic AKI remains unclear. Here,
      gefitinib, a highly selective EGFR inhibitor, abrogated LPS-induced
      phosphorylation of EGFR, ERK1/2, and STAT3 as well as expression of COX, eNOS,
      and proinflammatory cytokines in HK-2 cells. In addition, c-Src is an upstream of
      EGFR signaling pathway and mediates LPS-induced EGFR transactivation. In vivo,
      either gefitinib or genetic approaches (Wave-2 mutant mice, which have reduced
      EGFR tyrosine kinase activity) protected against LPS or cecal ligation and
      puncture (CLP) induced AKI respectively. Interestingly, the beneficial effects of
      gefitinib or genetic approaches were accompanied by the dephosphorylation of
      EGFR, ERK1/2, and STAT3, the down regulation of expression of COX, eNOS,
      macrophage infiltration, proinflammatory cytokines production and the renal cell
      apoptosis. Furthermore, mRNA array results indicated that gene families involved
      in cell death, inflammation, proliferation and signal transduction were down
      regulated in Wave-2 (Wa-2) mice. Take together, these data suggest that EGFR may
      mediate renal injury by promoting production of inflammatory factors and cell
      apoptosis. Inhibition of EGFR may have therapeutic potential for AKI during
      endotoxemia.

PMID- 29207669
TI  - Breath analysis by gas chromatography-mass spectrometry and electronic nose to
      screen for pleural mesothelioma: a cross-sectional case-control study.
AB  - Rationale: Malignant pleural mesothelioma (MPM) is mainly caused by previous
      exposure to asbestos fibers and has a poor prognosis. Due to a long latency
      period between exposure and diagnosis, MPM incidence is expected to peak between
      2020-2025. Screening of asbestos-exposed individuals is believed to improve early
      detection and hence, MPM management. Recent developments focus on breath analysis
      for screening since breath contains volatile organic compounds (VOCs) which
      reflect the cell's metabolism. Objectives: The goal of this cross-sectional, case
      control study is to identify VOCs in exhaled breath of MPM patients with gas
      chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen
      for MPM using an electronic nose (eNose). Methods: Breath and background samples
      were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former
      asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related
      diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and
      eNose. Results: Using GC-MS, AEx individuals were discriminated from MPM patients
      with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and
      cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients
      were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74%
      accuracy, respectively. The sensitivity, specificity, positive and negative
      predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for
      eNose, respectively. Conclusion: This study shows accurate discrimination of
      patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and
      eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis
      for MPM screening.

PMID- 29207670
TI  - MicroRNA-92b inhibits epithelial-mesenchymal transition-induced migration and
      invasion by targeting Smad3 in nasopharyngeal cancer.
AB  - Increasing studies reports that aberrant miRNAs contribute to nasopharyngeal
      carcinoma (NPC) development and progression. However, the role of miR-92b in NPC
      remains unclear. In present research, we found that a reduced miR-92b expression
      in NPC tissues and cell lines. The clinical data showed that the down-regulated
      miR-92b expression was obviously associated with adverse prognostic
      characteristic. Furthermore, we confirmed that miR-92b was a novel independent
      prognostic symbol for predicting 5-year survival of NPC patients. MiR-92b
      overexpression inhibited cell migration, invasion and EMT progress, while down
      regulated miR-92b reversed the effect. Besides, miR-92b could modulate Smad3 by
      directly binding to its 3'-UTR. In clinical samples of NPC, miR-92b inversely
      correlated with Smad3. Alternation of Smad3 expression at least partially
      abrogated the migration, invasion and EMT progress of miR-92b on NPC cells. In
      summary, our results indicated that miR-92b functioned as a tumor suppressor gene
      in regulating the EMT and metastasis of NPC via targeting Smad3, and may
      represent a novel potential therapeutic target and prognostic marker for NPC.

PMID- 29207671
TI  - Ginkgo biloba extract EGb 761-induced upregulation of LincRNA-p21 inhibits
      colorectal cancer metastasis by associating with EZH2.
AB  - EGb 761, the standard ginkgo biloba extract, is frequently prescribed in
      traditional Chinese medicine. Currently, there is no research focusing on its
      role in human colorectal cancer progression. In our study, we determined the anti
      metastatic effect of EGb 761 on colorectal cancer cells and further explored the
      potential underlying regulatory mechanism. The cell migration and invasion assay
      indicated that EGb 761 treatment of colorectal cancer cells induced inhibition of
      cell migration and invasion ability in a concentration-dependent manner. To
      further explore the underlying regulatory mechanisms that may account for these
      findings, we performed quantitative real-time PCR (RT-qPCR), western blotting and
      immunoprecipitation analysis. The results showed that EGb 761 induced
      upregulation of LincRNA-p21 expression in a dose- and time-dependent manner.
      Overexpression of LincRNA-p21 also suppressed colorectal cancer cell metastasis.
      Furthermore, EGb 761 as well as LincRNA-p21 inhibited the expression of
      extracellular matrix protein, fibronectin. More importantly, RNA
      immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed
      that LincRNA-p21 directly interacted with EZH2, and this interaction suppressed
      the expression of fibronectin. Finally, the gain and loss function assay revealed
      that EGb 761 inhibited migration, invasion and fibronctin expression by the
      LincRNA-p21/EZH2 pathway in colorectal cancer cells. Hence, EGb 761 may be a
      promising treatment regimen for colorectal cancer and restoration of LincRNA-p21
      levels may be helpful for enhancing the anti-cancer effect of EGb 761.

PMID- 29207672
TI  - Thoracic endovascular aortic repair for type B aortic dissection after renal
      transplantation.
AB  - Thoracic endovascular repair (TEVAR) is an effective treatment for type B aortic
      dissection (TBAD). Here, we evaluated the early-midterm effectiveness and safety
      of TEVAR for treating TBAD patients after renal transplantation. Six patients
      with TBAD treated with TEVAR after renal transplantation were recruited between
      February 2012 and December 2016. They were then followed up with clinical
      examinations and computed tomography angiography (CTA). TEVAR was successfully
      performed in all patients (100%), and the primary tear sites were well covered by
      stents with or without coverage of the left subclavian artery. No severe
      complications occurred in any patient during perioperative period. The one-year
      survival rate was 100%, one patient died of renal graft failure and heart failure
      four years after TEVAR; the remaining five patients (83.3%) survived and
      exhibited no severe complications. Our findings show that TEVAR provides
      satisfactory short-midterm results for TBAD patients after renal transplantation.
      Moreover, our experience shows that it need relative longer proximal landing zone
      to prevent the endoleak and recurrence. However, regular hematodialysis, long
      term immunosuppressive therapy, and blood pressure control remain crucial factors
      to prolong survival. Long-term follow-up studies are needed to evaluate the long
      term prognosis in these patients.

PMID- 29207673
TI  - Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and
      genotype in glioblastoma.
AB  - Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo
      the most malignant tumor areas, the extent of tumor infiltration and the sites
      giving origin to GB stem cells (GSCs), we combined positron emission
      tomography/computed tomography (PET/CT) and conventional and advanced magnetic
      resonance imaging (MRI) with histology, immunohistochemistry and molecular
      genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens
      [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions]
      from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy
      technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum
      standardized uptake value (18F-FDG SUVmax), relative cerebral blood volume
      (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and
      Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded
      to the most malignant tumor phenotype, to the greatest molecular spectrum and
      stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and
      fractional anisotropy (FA) in the CE region were very variable. 18F-FDG SUVmax,
      Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor
      infiltration. In edematous areas, reactive astrocytes and microglia/macrophages
      were influencing variables. Combined MRI and 18F-FDG PET/CT allowed to recognize
      the specific biological significance of the different identified areas of GB.

PMID- 29207674
TI  - Genetic polymorphisms in caveolin-1 associate with breast cancer risk in Chinese
      Han population.
AB  - Caveolin-1(CAV-1) was demonstrated to be a tumor suppressor gene and be
      implicated in the development of breast cancer (BC). Numerous potentially
      functional polymorphisms in CAV-1 have been identified, but their effects on BC
      were not clear. This case-control study aims to evaluate the relationship between
      CAV-1 polymorphisms and BC risk. 560 BC patients and 583 healthy controls were
      enrolled in the present study, all from Chinese Han population. We detected 3
      single nucleotide polymorphisms (rs3807987, rs1997623, and rs7804372) in CAV-1
      using the Sequenom MassARRAY method. The association between CAV-1genotypes and
      BC risk was assessed in six genetic models by calculating the odds ratio (OR) and
      95% confidence intervals (95% CIs) with chi2-test. The CAV-1 rs3807987
      polymorphism was observed to increase the risk of BC And the A allele of
      rs3807987 relates to a larger tumor size (>=2cm) and lower incidence of PR
      positive BC while the AA genotype of rs7804372 associates with a higher ER and
      Her-2 positive rate among BC patients. In addition,
      Ars1997623Grs3807987Trs7804372 haplotype was linked to a decreased risk of BC (OR
      =0.64, 95%CI=0.44-0.93), whereas Crs1997623Ars3807987Trs7804372 haplotype was
      related to an increased BC risk (OR =1.74, 95%CI=1.04-2.92). Our study suggests
      that CAV-1 rs3807987 can increase the BC risk among Chinese Han women. And the
      rs3807987 and rs7804372 in CAV-1 may serve as predictors for prognosis of BC.

PMID- 29207675
TI  - Thio-barbiturate-derived compounds are novel antioxidants to prevent LPS-induced
      inflammation in the liver.
AB  - Liver inflammation is closely associated with metabolic syndrome. Oxidative
      stress plays a synergistic role in inflammation by activating nuclear factor
      kappa B (NF-kappaB) signaling in the liver. Therefore, substantial efforts have
      been made to develop compounds that inhibit the generation of oxidative stress
      and activation of NF-kappaB. We synthesized twenty-six novel 5-(substituted
      benzyl)-2-oxo- and 5-(substituted benzyl)-2-thioxo-dihydropyrimidine-4,6(1H,5H)
      dione derivatives for the development of potential antioxidants and examined
      their biological activities in vitro and in vivo. Thio-barbiturate-derived
      compounds 5-[4-hydroxy-3-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]-dione
      (2d) and 5-[4-hydroxy-3,5-methoxybenzy]-2-thioxodihydropyrimidine-4,6[1H,5H]
      dione (2l) had the strongest inhibitory effect on reactive oxygen species and
      peroxynitrite generation in vitro. Furthermore, oral administration of compounds
      2d and 2l in mice notably suppressed lipopolysaccharide (LPS)-induced oxidative
      stress and NF-kappaB activation in the liver. Because macrophages play an
      essential role in liver inflammation, we investigated the effects of these
      compounds on inflammatory signaling in LPS-induced RAW264.7 macrophages. LPS
      induced NF-kappaB activation and protein expression of cyclooxygenase 2 and
      inducible nitric oxide synthase were inhibited by pretreatment of these compounds
      in macrophages. In parallel with this finding, the phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN) and AKT signalings, which are upstream activators
      of p65, were decreased by these compounds in macrophages. Our study suggests that
      compounds 2d and 2l inhibit oxidative stress and NF-kB-mediated inflammation, at
      least partially, through suppressing PTEN/AKT signaling. Therefore, these
      compounds may be useful as therapeutic agents for the amelioration of
      inflammatory diseases.

PMID- 29207676
TI  - Circular RNA hsa_circ_000984 promotes colon cancer growth and metastasis by
      sponging miR-106b.
AB  - Circular RNAs (circRNAs) as a novel type of noncoding RNAs (ncRNAs) are widely
      studied in the development of human various diseases, including cancer. Here, we
      found circular RNA hsa_circ_000984 encoded by the CDK6 gene was remarkably
      upregulated in the tissues of colorectal cancer (CRC) patients and in the CRC
      cell lines. Moreover, high expression level of hsa_circ_000984 was significantly
      associated with advanced colorectal cancer. Further analysis revealed that
      hsa_circ_000984 knockdown could inhibit cell proliferation, migration, invasion
      in vitro and tumor formation in vivo in CRC cell lines. Mechanically, we found
      that hsa_circ_000984 may act as a competing endogenous RNA (ceRNA) by
      competitively binding miR-106b and effectively upregulate the expression of CDK6,
      thereby inducing a series of malignant phenotypes of tumor cells. Taken together,
      these observations suggest that the hsa_circ_000984 could mediate the expression
      of gene CDK6 by acting as a ceRNA, which may contribute to a better understanding
      of between the regulatory miRNA network and CRC pathogenesis.

PMID- 29207677
TI  - Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer
      risk: a meta-analysis of epidemiological studies.
AB  - The relationship between intake of fish and n-3 fatty acids and endometrial
      cancer risk has not been consistent across epidemiological studies. We
      quantitatively assessed the aforementioned association through a systematic
      review and meta-analysis. PubMed and Embase were searched through March 2017 for
      eligible epidemiological studies. Fixed or random-effects models were used to
      pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response
      relationship was also evaluated. Based on the literature search, five prospective
      studies and 11 case-control studies were identified. All 16 studies were
      categorized as high-quality studies. After pooling available risk estimates, no
      significant association was detected between overall fish intake and endometrial
      cancer risk. In subgroup analyses, every one additional serving/week of fish
      intake was significantly associated with inversed endometrial cancer risk in
      studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies
      performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested
      subgroups. In studies conducted in Asia, there was significant positive
      association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake,
      marginally inverse associations of high EPA or DHA intake were detected (EPA: RR
      (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response
      analyses suggested a significant nonlinear relationship between DHA intake and
      endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that
      intake of n-3 PUFA may be inversely associated with endometrial cancer risk at
      some level of evidence, although the exact relationship, especially for fish
      intake, needs further characterization. Further well-designed studies are
      warranted.

PMID- 29207678
TI  - Systematic review and meta-analysis of the prognostic value of preoperative
      platelet-to-lymphocyte ratio in patients with urothelial carcinoma.
AB  - A large number of studies have investigated the prognostic value of the platelet
      to-lymphocyte ratio (PLR) in patients diagnosed with urothelial carcinoma, but
      the evidence from these papers is conflicting. This systematic review and meta
      analysis was carried out to assess the role of PLR in urothelial carcinoma
      patients. After a systematic search of the PubMed, Embase, Web of science
      databases, the associations between PLR and overall survival (OS), cancer
      specific survival (CSS)/disease-specific survival (DSS), and relapse-free
      survival (RFS)/disease-free survival (DFS) were analyzed in urothelial carcinoma
      patients. The relationship between PLR and pathological results was also
      evaluated. A total of seven studies (eight cohorts) comprising 3171 patients were
      included. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs)
      indicated the increased preoperative PLR predicted poor OS (HR = 1.14, 95% CI =
      1.01- 1.27, p < 0.001), CSS/DSS (HR = 1.24, 95% CI = 1.08-1.40, p < 0.001),
      RFS/DFS (HR = 1.23, 95% CI = 1.09-1.38, p < 0.001). However, no significant
      correlation was found between elevated preoperative PLR and pathological results
      such as tumor grade, tumor necrosis and T stages. These findings suggest a high
      PLR is associated with reduced OS, CSS/DSS and RFS/DFS in urothelial carcinoma.
      Preoperative PLR may therefore be a predictive factor in this patient group.

PMID- 29207679
TI  - Italian real life experience with brentuximab vedotin: results of a large
      observational study on 234 relapsed/refractory Hodgkin's lymphoma.
AB  - A large Italian multicenter observational retrospective study was conducted on
      the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma
      (HL) to check if clinical trial results are confirmed even in a real life
      context. 234 CD30+ HL patients were enrolled. Best response was observed after a
      median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a
      complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall
      response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best
      response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR.
      Disease free survival was 26.3% at 3 years and progression free survival 31.9% at
      4.5 years. Duration of response did not differ for who achieved at least PR and
      then either did or did not undergo consolidative transplant. Overall, the
      treatment was well tolerated and no death has been linked to BV-induced toxicity.
      Our report confirms activity in elderly patients, duration of response unrelated
      to the consolidation with transplant procedure, the relevance of the CR status at
      first restaging, and the role of BV as a bridge to transplant for chemorefractory
      patients.

PMID- 29207680
TI  - Correlation between cerebellar metabolism and post-stroke depression in patients
      with ischemic stroke.
AB  - The neurochemical changes that occur in the brain of patients with post-stroke
      depression (PSD) are not fully understood. This study aims to explore the
      correlation between cerebellar metabolism changes and PSD using proton magnetic
      resonance spectroscopy (1H-MRS). Participants were assigned to 3 groups: 60
      patients with PSD (PSD group), 60 stroke patients without depression (NOPSD
      group), and 60 healthy volunteers (HEAL group). T1 WI, T2 WI, DWI and 1H-MRS
      examination were performed for patients at 14 days, 3 months after the stroke,
      respectively, and for healthy volunteers once when included in the study. Cho/Cr
      and Cho/NAA ratios in the cerebellar hemisphere contralateral to the lesion were
      higher in the PSD group than those in the HEAL and NOPSD groups on 14th day after
      the stroke (P < 0.05). In PSD group, Cho/Cr and Cho/NAA ratios in the cerebellar
      hemisphere contralateral to the lesion were positively correlated to the HAMD
      scale scores at both 14 days and 3 months after stroke (P < 0.05); Higher Cho/Cr
      and Cho/NAA ratios, and lower NAA/Cr ratio in the cerebellar hemisphere
      contralateral to the lesion were observed at 3 months after stroke compared to
      that at 14 days after stroke. Cerebellar damage may lead to PSD, and the degree
      of cerebellar damage may be associated with severity of PSD.

PMID- 29207681
TI  - Histone demethylase JMJD2C: epigenetic regulators in tumors.
AB  - Histone methylation is one of the major epigenetic modifications, and various
      histone methylases and demethylases participate in the epigenetic regulating.
      JMJD2C has been recently identified as one of the histone lysine demethylases. As
      one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to
      demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9)
      or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting
      heterochromatin formation, genomic imprinting, X-chromosome inactivation, and
      transcriptional regulation of genes. JMJD2C was firstly found to involve in
      embryonic development and stem cell regulation. Afterwards, aberrant status of
      JMJD2C histone methylation was observed during the formation and development of
      various tumors, and it has been reported to play crucial roles in the progression
      of breast cancer, prostate carcinomas, osteosarcoma, blood neoplasms and so on,
      indicating that JMJD2C represents a promising anti-cancer target. In this review,
      we will focus on the research progress and prospect of JMJD2C in tumors, and
      provide abundant evidence for the functional application and therapeutic
      potential of targeting JMJD2C in tumors.

PMID- 29207683
TI  - Non-coding RNA: a potential biomarker and therapeutic target for sepsis.
AB  - Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities
      caused by an altered systemic host response to infection, has become the main
      cause of death among patients admitted to the intensive care units. Recently,
      genome-wide expression analysis revealed that over 80% of the essential genetic
      elements were altered in critically ill patients. Notably, non-coding RNAs,
      including microRNAs, long non-coding RNAs and circular RNAs, have been proven to
      play essential roles in innate immunity, mitochondrial dysfunction and organ
      dysfunction. In this review, we introduced the biogenesis of non-coding RNAs
      briefly and summed up different kinds of non-coding RNAs in regulation of sepsis,
      which could provide a more comprehensive understanding about pathogenesis of the
      disease. Additionally, we summarized the limitations of current biomarkers and
      then recommended some non-coding RNAs as novel potential biomarkers for sepsis
      and sepsis-induced organ dysfunction. Besides, we also introduced some problems
      and challenges that need to be overcome during the clinical application of non
      coding RNAs. Future research should focus on elucidating their molecular
      mechanisms, particularly long non-coding RNAs as well as circular RNAs and
      sepsis, to further understanding of the disease process. With the in-depth
      understanding of the mechanism of sepsis, non-coding RNAs provide a new insight
      into sepsis and could become the novel therapeutic targets in the future.

PMID- 29207684
TI  - Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.
AB  - Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in
      adults. With a median patient survival of less than two years, GBM represents one
      of the biggest therapeutic challenges of the modern era. Even with the best
      available treatment, recurrence rates are nearly 100% and therapeutic options at
      the time of relapse are extremely limited. Nivolumab, an anti-programmed cell
      death-1 (PD-1) monoclonal antibody, has provided significant clinical benefits in
      the treatment of various advanced cancers and represented a promising therapy for
      primary and recurrent GBM. CheckMate 143 (NCT 02017717) was the first large
      randomized clinical trial of PD pathway inhibition in the setting of GBM,
      including a comparison of nivolumab and the anti-VEGF antibody, bevacizumab, in
      the treatment of recurrent disease. However, preliminary results, recently
      announced in a WFNOS 2017 abstract, demonstrated a failure of nivolumab to
      prolong overall survival of patients with recurrent GBM, and this arm of the
      trial was prematurely closed. In this review, we discuss the basic concepts
      underlying the rational to target PD pathway in GBM, address implications of
      using immune checkpoint inhibitors in central nervous system malignancies,
      provide a rationale for possible reasons contributing to the failure of nivolumab
      to prolong survival in patients with recurrent disease, and analyze the future
      role of immune checkpoint inhibitors in the treatment of GBM.

PMID- 29207682
TI  - Over forty years of bladder cancer glycobiology: Where do glycans stand facing
      precision oncology?
AB  - The high molecular heterogeneity of bladder tumours is responsible for
      significant variations in disease course, as well as elevated recurrence and
      progression rates, thereby hampering the introduction of more effective targeted
      therapeutics. The implementation of precision oncology settings supported by
      robust molecular models for individualization of patient management is warranted.
      This effort requires a comprehensive integration of large sets of panomics data
      that is yet to be fully achieved. Contributing to this goal, over 40 years of
      bladder cancer glycobiology have disclosed a plethora of cancer-specific glycans
      and glycoconjugates (glycoproteins, glycolipids, proteoglycans) accompanying
      disease progressions and dissemination. This review comprehensively addresses the
      main structural findings in the field and consequent biological and clinical
      implications. Given the cell surface and secreted nature of these molecules, we
      further discuss their potential for non-invasive detection and therapeutic
      development. Moreover, we highlight novel mass-spectrometry-based high-throughput
      analytical and bioinformatics tools to interrogate the glycome in the postgenomic
      era. Ultimately, we outline a roadmap to guide future developments in glycomics
      envisaging clinical implementation.

PMID- 29207685
TI  - Excellent response to chemotherapy post immunotherapy.
AB  - Introduction: Immunotherapy in the form of immune checkpoint inhibitors has
      changed the landscape of cancer treatment. Newer monoclonal antibodies are coming
      up and are being tested in various cancers during different stages of treatment.
      With the increasing use of immune checkpoint inhibitors in the management of
      various types of cancers, the question is raised as to what next can be offered
      to a patient who has progressed on this newer treatment. Does Sequence matter?
      There have been reports of improved responses to chemotherapy after immunotherapy
      in the form of vaccines. Here we present a case series of 6 patients who
      progressed on immunotherapy with immune checkpoint inhibitors after initial
      modality of treatment (chemotherapy/radiation), subsequently received
      chemotherapy with excellent response. Methods: We have a cohort of six patients
      who had disease progression on second line Immunotherapy for solid or
      hematological malignancies and had ECOG < 2. All these patients received third
      line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2
      had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell
      lymphoma. Prior review and approval were obtained from our institutional review
      board. Results: All patients had an excellent response to chemotherapy in third
      line setting, after immune checkpoint inhibitors and most of them achieved a
      complete response. Conclusion: Targeting cancer with chemotherapy after failure
      of immunotherapy is a valid option and can lead to better response rates and PFS
      which may lead to OS. This effect may be secondary to immunotherapy removing the
      inhibition exerted by tumor cells or other immune cells initially followed by
      cytotoxic chemotherapy mediated killing of tumor cells.

PMID- 29207686
TI  - Molecular targeting of the Aurora-A/SMAD5 oncogenic axis restores
      chemosensitivity in human breast cancer cells.
AB  - Although the majority of breast cancers initially respond to the cytotoxic
      effects of chemotherapeutic agents, most breast cancer patients experience tumor
      relapse and ultimately die because of drug resistance. Breast cancer cells
      undergoing epithelial to mesenchymal transition (EMT) acquire a CD44+/CD24
      /ALDH1+ cancer stem cell-like phenotype characterized by an increased capacity
      for tumor self-renewal, intrinsic drug resistance and high proclivity to develop
      distant metastases. We uncovered in human breast tumor xenografts a novel non
      mitotic role of Aurora-A kinase in promoting breast cancer metastases through
      activation of EMT and expansion of breast tumor initiating cells (BTICs). In this
      study we characterized the role of the Aurora-A/SMAD5 oncogenic axis in the
      induction of chemoresistance. Breast cancer cells overexpressing Aurora-A showed
      resistance to conventional chemotherapeutic agents, while treatment with
      alisertib, a selective Aurora-A kinase inhibitor, restored chemosensitivity.
      Significantly, SMAD5 expression was required to induce chemoresistance and
      maintain a breast cancer stem cell-like phenotype, indicating that the Aurora
      A/SMAD5 oncogenic axis promotes chemoresistance through activation of stemness
      signaling. Taken together, these findings identified a novel mechanism of drug
      resistance through aberrant activation of the non-canonical Aurora-A/SMAD5
      oncogenic axis in breast cancer.

PMID- 29207687
TI  - Variation in Morphometry of Vastus Medialis Muscle.
AB  - Introduction: The Vastus Medialis (VM) muscle divides into two parts, proximal
      Vastus Medialis Longus (VML) and distal Vastus Medialis Obliquus (VMO). The VMO
      originates from the tendon of adductor magnus and insert into the medial border
      of patella and these fibers are nearly horizontal. It exerts medial force vector
      to counter the lateral force vector of Vastus Lateralis (VL) hence the VM
      presents a biomechanical advantage over the VL. The functional importance of VML
      and VMO is well explained but the anatomical evidence of separate identity of VMO
      is lacking. Aim: To determine muscle fiber angles and lengths of VML and VMO, to
      find out the distinct nerve supply and fascial plane between VML and VMO and to
      evaluate VM insertion in relation to patella. Materials and Methods: Thirty
      intact lower limbs (right-15 and left- 15) from 15 donated cadavers with an age
      60 years and above were dissected. Lengths and angles of VML, VMO superior (VMOs)
      and VMO inferior (VMOi) were measured. The fascial plane and the femoral nerve
      and its branches supplying VM were dissected and terminal branches were traced in
      each section with the blunt dissection. All parameters were recorded and
      statistical analysis was done using one-way ANOVA. Results: The VMO took origin
      from the adductor magnus muscle and attached to the patella. VMOi was present in
      83.33% cases (25 limbs), and inserted to the medial border of patella. The
      percentages of VML, VMOs and VMOi lengths compared to total VM length were
      65.54+/-4.84, 25.23+/-4.20 and 9.22+/-2.17 respectively. The fiber angles ranged
      for VML, VMOs and VMOi were between 18 to 32, 30 to 46 and 46 to 56 degrees
      respectively. There were significant differences among all groups (p=0.001).
      These two parts were not separated by distinct fascial plane and no separate
      nerve supply was observed but the richest nerve supply to VMO was noted.
      Conclusion: The present study conclude that VMO is having obtuse angle,
      horizontal fibers and richest nerve supply as compared to proximal part which
      make it functionally as a separate entity but not anatomically.

PMID- 29207688
TI  - Radiological Biometric Study of Metatarsals and Phalanges.
AB  - Introduction: Several diseases affect the forefoot bones. Relative dimensions of
      the forefoot bones are important considerations for preoperative and
      postoperative assessment of surgeries. The choice of a particular surgery over
      another can also be made if the surgeon knows the length to which a bone needs to
      be lengthened or shortened in comparison to other bones of the forefoot. Aim: To
      measure the dimensions of the metatarsals and phalanges on standardized
      radiographs and to determine possible correlations amongst them. Materials and
      Methods: A cross-sectional prospective study was conducted on 60 volunteer
      participants of either sex. The dimensions of metatarsals and phalanges were
      measured on standardized radiographs of both feet in 60 healthy adults. The mean,
      range and standard deviation were calculated. Correlation analysis was done to
      assess the association between the variables. Results: The first metatarsal was
      the shortest (56.42+/-4.41 mm in males and 50.09+/-3.06 mm in females) and widest
      of all metatarsals (13.7+/-1.00 mm in males and 11.7+/-0.91 mm in females). The
      first proximal phalanx was the longest (28.0+/-2.40 mm in males and 25.8+/-2.21
      mm in females) and the fifth distal phalanx (5.2+/-1.33 mm in males and 4.4+/
      1.03 mm in females) was the shortest of all phalanges. A strong correlation
      (p<0.001) exists amongst the lengths of metatarsals, proximal phalanges and
      middle phalanges, within their own groups. Conclusion: Correlation of the lengths
      and widths of the forefoot bones amongst themselves and between types can be
      calculated mathematically utilising standardized radiographs. This helps in
      assessment of forefoot disorders, choose an appropriate surgical technique and
      postoperative evaluation.

PMID- 29207689
TI  - Students' Perception and Attitude on Methods of Anatomy Teaching in a Medical
      College of West Bengal, India.
AB  - Introduction: Incorporating newer teaching aids over traditional one in Anatomy
      has been challenging both for the teachers and the learners. Different
      educational strategies are being used for teaching of Anatomy. Aim: To elicit the
      perception and attitude toward teaching approaches in the Anatomy curriculum
      among first year medical students. Materials and Methods: A cross-sectional,
      descriptive study was undertaken with the help of predesigned, pre-tested
      questionnaire to elicit knowledge in four domains of classroom teaching which
      were: a) gross anatomical structure; b) organ identification; c) topography; and
      d) radiological anatomy and self-assessment of acquired skills in respective
      fields among 114 first year students. Results: A total of 57% of students opined
      good in gross structure of anatomy. A 60.5% of students preferred chalk and board
      method and 33.3% with LCD projector. Regarding acquiring knowledge, 72.8% of
      medical students gathered knowledge in gross anatomical structure domain whereas
      58.8% in radiological anatomy. The overall mean score of attitude of the students
      regarding incorporating newer techniques in Anatomy teaching is 14.17+/-2.26.
      Conclusion: The perception of Anatomy teaching and attitude among medicos have
      been studied and opinion from them had thrown light for incorporation of newer
      techniques in their teaching curriculum.

PMID- 29207690
TI  - Morphological and Morphometric Study of Coronary Sinus in North Indian
      Population.
AB  - Introduction: Coronary sinus (CS) is the largest vein draining the blood from
      heart. It is a muscular tube of about 2 cm to 3 cm length and 1 cm in caliber. It
      has become a clinically important structure through its role in providing access
      for different cardiac procedures viz., biventricular pacing, arrhythmia ablation
      and for deployment of an array of cardiac devices. Aim: To study the location,
      shape, length and width of CS including its left atrial muscular coverage in 50
      cadaveric hearts. Materials and Methods: The present study comprised of 50 adult
      human apparently normal formalin fixed cadaveric hearts belonging to either sex
      obtained from the Department of Anatomy, Government Medical College, Amritsar,
      India. Location and shape of CS were noted, external and internal lengths of the
      CS were measured with the help of a thread and Vernier caliper. Width of CS was
      measured at three levels; at the beginning, at the point of entry of Middle
      Cardiac Vein (MCV) and at termination in right atrium. The walls of CS were
      examined to note whether they were covered by the muscles of left atrium or not.
      Descriptive analysis was done to calculate range, mean and Standard Deviation
      (SD) by using Statistical Package for Social Science (SPSS) 17.0. Results: CS was
      located in the posterior atrioventricular sulcus in 98%. Two shapes; funnel in
      82% and tubular/cylindrical in 18% were observed. External length of coronary
      sinus ranged from 20.5 mm to 58.78 mm (mean 38.22+/-8.6 mm) and internal length
      ranged from 16.28 mm to 49.6 mm (mean 34.48+/-8.9 mm). Maximum width of coronary
      sinus was at its termination (9.61+/-2.6 mm) and it was covered by muscles of
      left atrium in 96% of hearts. Conclusion: CS is a constant structure in cardiac
      venous anatomy but its location, shape, length and width are variable. Knowing
      these variations can help cardiac surgeons especially during cardiac
      resynchronization therapy, ablation and defibrillation.

PMID- 29207691
TI  - A Comparative Study of High Sensitivity C-Reactive Protein and Metabolic
      Variables in Type 2 Diabetes Mellitus with and without Nephropathy.
AB  - Introduction: Diabetic nephropathy is a serious chronic complication of Type 2
      Diabetes Mellitus (T2DM) which impairs the quality of life, leading to increased
      morbidity and mortality. The high sensitivity C-reactive protein (hs-CRP) is an
      acute phase reactant which acts as a non-specific systemic marker of
      inflammation. Aim: To find out the relationship between serum hs-CRP and
      metabolic variables in Type 2 diabetic patients with and without nephropathy.
      Materials and Methods: The study group consists of 96 subjects that include non
      diabetic healthy controls, Type 2 diabetic patients without any complications and
      patients with diabetic nephropathy. The study group was composed of both genders,
      aged 31-70 years, who reported after 10-12 hours overnight fasting; then, venous
      blood and fresh urine samples were collected, in the morning from all the study
      subjects. Data were analysed using Statistical Package for the Social Sciences
      (SPSS). Independent t-test was used to compare between the groups and Chi square
      test was used to find out the relationship between serum hs-CRP and metabolic
      variables. Results: The results showed a significantly (p<0.05) increasing trend
      of serum hs-CRP with the degree of microalbumin excretion and the severity of
      nephropathy in Type 2 diabetic patients. The result showed a significant (p<0.05)
      relationship between hs-CRP and the metabolic variables like Fasting Blood
      Glucose (FBG), Post Prandial Blood Glucose (PPBG), Total Cholesterol (TC),
      Triglycerides (TG), LDL-Cholesterol (LDL-C), TC:HDL-Cholesterol (HDL-C) ratio and
      estimated Glomerular Filtration Rate (eGFR) and no significance (p>0.05) between
      hs-CRP and HDL-Cholesterol in both diabetic and diabetic nephropathy subjects.
      Conclusion: Hs-CRP was strongly associated with the metabolic variables and
      predictors of cardiovascular risk in Type 2 diabetes mellitus with and without
      nephropathy. The hs-CRP might be considered as a predictor or illness indicator
      for the development of nephropathy and cardiovascular risk in Type 2 diabetic
      patients.

PMID- 29207692
TI  - Oxidative Stress in the Development of Genetic Generalised Epilepsy: An
      Observational Study in Southern Indian Population.
AB  - Introduction: Oxidative stress resulting from excessive generation of Reactive
      Oxygen Species (ROS) plays a significant role in neurodegeneration associated
      with seizures/epilepsy. Aim: To evaluate oxidative stress markers and antioxidant
      enzymes in Genetic Generalised Epilepsy (GGE) and to know the extent of oxidative
      stress induced by Anti-Epileptic Drugs (AEDs) with the time duration of
      treatment. Materials and Methods: In this case-control study, 310 GGE patients
      (male:female=203:107), who were on AED treatment (n=235) and 75 untreated
      patients (male:female=49:26) along with 310 age and sex matched healthy controls
      were recruited. Oxidative stress markers such as Nitric Oxide (NO),
      Malondialdehyde (MDA) and antioxidant enzyme activities namely Superoxide
      Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT) were measured
      spectrophotometrically. Results: Significantly higher levels of serum NO, MDA and
      low levels of plasma Total Antioxidant Capacity (TAC) were found in patients as
      compared to controls (p<0.001) whereas erythrocyte SOD, CAT and GPx activities
      were found to be significantly low in patients when compared to the control group
      (p<0.001). Statistically significant higher levels of NO, MDA and lower levels of
      SOD, CAT and TAC were observed in patients subgroup, who were on AEDs for more
      than >5 years compared to other groups (<= 1 year and 1-<= 5 years) (p=0.02,
      p=0.01, p=0.001, p=0.01 and p=0.05 respectively). Further, significant increase
      in the levels of NO, MDA and decreased activities of SOD, CAT were found in
      treated patients compared to untreated patients (p<0.05) denoting that additional
      oxidative stress induced by AEDs which results in seizure recurrence and drug
      intractability. Conclusion: Our study demonstrated that GGE patients have
      additional oxidative stress due to AEDs and decreased antioxidant enzyme
      activities causing an imbalance between oxidant and antioxidant status, which
      might contribute to the pathogenesis of GGE.

PMID- 29207693
TI  - Serum Uric Acid in Chronic Obstructive Pulmonary Disease: A Hospital Based Case
      Control Study.
AB  - Introduction: Airway inflammation and imbalance between oxidant/anti-oxidant
      mechanisms are postulated to play a major role in the pathogenesis and
      exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Previous studies on
      the role of serum Uric Acid (UA) in COPD subjects have been both confounding and
      inconclusive. Aim: To measure the serum UA levels among COPD subjects and to
      correlate with different stages of the disease. Materials and Methods: The study
      included 39 stable COPD subjects (21 males, 18 females; 13 smokers, 26
      nonsmokers; age group; 40 to 60 years) and compared with 46 control subjects from
      the general population. Serum UA levels were measured by enzymatic colorimetric
      assay in fully automated analyser (Cobas Integra 400+, Roche, Germany) using
      commercially available kits from Roche. This was further correlated with duration
      and severity of COPD {determined as per Global Initiative for Obstructive Lung
      Disease (GOLD) criteria}. Results: The mean age of COPD and control subjects was
      62.97+/-11.30 and 48.76+/-12.71 years, respectively (p<0.001). COPD cases had
      significantly higher level of UA compared to control subjects (4.85+/-1.67 vs.
      2.32+/-0.93 mg/dl, respectively, p<0.001). Female subjects with COPD had higher
      levels of UA compared to their male counterparts (5.15+/-1.89 vs. 4.59+/-1.45
      mg/dl, respectively, p=0.3). Similar insignificant (p=0.56) trend was also
      observed among control subjects. Hyperuricaemia correlated significantly (p<
      0.05) with advance duration (>= 10 years) of COPD; whereas, statistically
      insignificant trend was observed for GOLD stage 3/4 versus stage 1/2 disease.
      Nonsmokers were having higher uric acid level than smokers. Alcohol intake did
      not affect the level of uric acid in COPD cases (p=0.79). Conclusion: Serum uric
      acid is a simple, cost effective biochemical test which may be useful in risk
      stratification of subjects with newly diagnosed chronic obstructive pulmonary
      disease. Hyperuricaemia is associated with advance duration and stage of COPD.

PMID- 29207694
TI  - The Effect of Ramadan Fasting on Biochemical Parameters in Healthy Thai Subjects.
AB  - Introduction: Although, the effect of Ramadan fasting on the risks for
      Cardiovascular Disease (CVD) has been reported in several studies, the results
      were inconsistent. In addition, the effect of Ramadan fasting on biochemical
      parameters in Thai subjects has not been evaluated. Aim: The aim of this study
      was to investigate the effect of Ramadan fasting on anthropometry, blood
      pressure, Fasting Blood Glucose (FBG), lipid profiles, and body composition in
      healthy Thai subjects. Materials and Methods: A total of 65 healthy subjects (21
      men and 44 women) aged between 19-24 years were randomly recruited.
      Anthropometry, blood pressure, FBG, Total Cholesterol (TC), Triglyceride (TG),
      High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol
      (LDL-C), and body composition were measured before Ramadan, end of Ramadan and
      after one month of Ramadan. Results: There were no changes in anthropometry,
      blood pressure, lipid profiles and body composition in both genders before
      Ramadan, end of Ramadan and after one month of Ramadan. Nevertheless, FBG levels
      were significantly increased after one month of Ramadan compared with baseline
      (5.09+/-0.50 versus 4.83+/-0.38 mmol/L, p=0.016, respectively) in women.
      Conclusion: The Ramadan fasting did not affect the lipid, anthropometric and body
      composition in healthy Thai subjects. However, the increased FBG levels after one
      month of Ramadan were observed in women. To improve the favourable biochemical
      parameters after Ramadan fasting, the lifestyle modifications such as, increased
      intake of healthy diets and increased physical activity should be recommended.

PMID- 29207695
TI  - Association of Glycated Haemoglobin and Serum Apolipoproteins with Diabetic
      Retinopathy: An Indian Overview.
AB  - Introduction: India is presently facing an epidemic of diabetes mellitus and the
      risks of chronic complications from the disease are associated with the duration
      of the disease as well as the degree of hyperglycaemia. Diabetic retinopathy is a
      known microvascular complication of diabetes mellitus and is the most common
      cause of blindness in the western countries.Apolipoproteins are the protein
      component of lipoproteins. Apart from acting as structural proteins, they also
      act as cofactors to various enzymes. Aim: To measure the levels of serum
      apolipoproteins and glycated haemoglobin in cases of diabetic retinopathy and to
      assess their association with the stages of diabetic retinopathy. Material and
      Methods: The 135 diabetic cases [with (110) and without (125) retinopathy]
      attending the Ophthalmology OPD of this tertiary care hospital were included in
      the present study. Following retinoscopy, the patients were classified as Non
      Proliferative Diabetic Retinopathy (NPDR) (n=75) and Proliferative Diabetic
      Retinopathy (PDR) (n=35). The controls (n=100) were age and sex matched patients
      who did not have diabetes. The cases and controls were assessed for HbA1c, total
      cholesterol, triglycerides, HDL cholesterol, Apo A-I and Apo B-100. Results: The
      HbA1c was found to be higher in diabetics without retinopathy (7.02%) as compared
      to controls (5.58%) (p<0.05) and the highest value was seen in the mild NPDR
      group (8.82%). The mean value of Apo A-I was found to be lowest in the diabetics
      without retinopathy at 88 mg/dl and the highest in severe NPDR at 167 mg/dL. The
      mean value of Apo B-100 was found to be highest in severe NPDR at 114 mg/dL. The
      mean value of HDL cholesterol was lowest in moderate NPDR at 36.6 mg/dl. Total
      cholesterol was highest in severe NPDR at 280.88mg/dl while triglyceride was
      highest in severe NPDR at 286.4mg/dl. Conclusion: In our study, the level of
      HbA1c was found to range from 5.58% in non-diabetic to 8.82% in mild NPDR. There
      was a clear association between Apo B-100 and total cholesterol, triglycerides
      with the highest value of each parameter seen in the severe NPDR group. There was
      a discordance noted in the levels of HDL and Apo A-I in various groups. Apo B-100
      values may be of value in prognosis of diabetic retinopathy as higher values may
      result in progression of the disease. Further studies involving Lp(a) and
      homocysteine may be required in cases of diabetic retinopathy.

PMID- 29207696
TI  - Correlation of Pregnancy Associated Plasma Protein A and Zinc with Calculated
      Risk Ratio of Dual Test.
AB  - Introduction: First trimester screening by dual test is the most preferred method
      of antenatal screening. The detection rate of foetal aneuploidy using dual test
      is 95%. This test uses maternal serum free beta human Chorionic Gonadotropin
      (free beta hCG) and Pregnancy Associated Plasma Protein A (PAPP-A) along with
      maternal demographic and foetal sonographic indices to calculate risk for foetal
      aneuploidy. PAPP-A is a zinc binding metalloproteinase which is also responsible
      for placental development and foetal growth. So, zinc might also have some role
      in first trimester screening. No studies are available substantiating the role of
      zinc in first trimester screening. Aim: To measure and correlate maternal serum
      zinc with PAPP-A and calculated risk ratio of first trimester screening.
      Materials and Methods: PAPP-A and zinc were measured from the serum of 84
      pregnant women aged 20-40 years in 11th-13th weeks+6 days of gestation who
      underwent dual test during their antenatal check-up. Risk calculation was done
      using Screening Software for Downs Windows Lab (SSDWL). Results: Maternal serum
      PAPP-A showed a significant positive correlation with maternal serum zinc (p
      value <0.001). Maternal serum PAPP-A and zinc both showed a significant positive
      correlation with calculated risk ratio (p-value<0.01). Conclusion: As PAPP-A is a
      zinc binding metalloproteinase, zinc showed significant pattern of correlation
      with aneuploidy risk as shown by PAPP-A. So there could be a possible role for
      serum zinc in first trimester of screening.

PMID- 29207697
TI  - Effects of Organophosphorus Pesticides on Cardiorespiratory Parameters among the
      Farmers.
AB  - Introduction: Indiscriminate use and improper handling of synthetic pesticides in
      agriculture have resulted in serious problems such as asthma, wheeze and chronic
      bronchitis among the farmers. Though number of studies have been done on
      pesticide exposure and its effect on cardiorespiratory parameters in Northern
      India, only few studies were done in Southern India, thus this study was chosen.
      Aim: To find the cardiorespiratory changes in farm workers exposed to
      organophosphorus pesticides. Materials and Methods: Peak Expiratory Flow Rate
      (PEFR), blood pressure, pulse rate were measured among 35 farm workers of Palayam
      and Naduveerpattu village of Cuddalore district and 35 age, sex, BMI matched
      controls were taken from urban area and the same parameters were measured in both
      groups from 10 am-12 am in the morning. History of use of personal protective
      equipments like face mask, eye mask, special clothes, shoes, hat, history of
      respiratory symptoms and hygienic work practices was also obtained from the
      farmers. Chi-square test was used to analyse the qualitative data. All values
      were expressed as Mean+/-SD. Students unpaired t-test was used to compare PEFR
      between two groups and to compare the duration of exposure and PEFR using GRAPH
      PAD PRISM. The p<0.05 was considered to be statistically significant. Results:
      There was a significant decrease in PEFR among the farmers (p<0.001) compared to
      the controls. On comparing the duration of exposure of pesticide and the PEFR
      values by unpaired Students t-test, there was a significant difference with p
      value of 0.03. Blood Pressure did not show any significant difference between the
      two groups. But the pulse rate was significantly decreased among the farmers
      (p<0.001) which could be due to their regular physical activity. About 71% of the
      farmers used personal protective equipments. Conclusion: Thus, chronic exposure
      to organophosphorus pesticides has an impact on PEFR among the farmers.

PMID- 29207698
TI  - Protective effects of Ethanolic Extract of Emblica officinalis (amla) on
      Cardiovascular Pathophysiology of Rats, Fed with High Fat Diet.
AB  - Introduction: Dietary high fat alters lipid profile and possibly induce sympatho
      vagal imbalance. Emblica officinalis is found to be potential antioxidant and
      possibly counteract hyperlipidemia induced lipid peroxidation. Aim: To assess
      Ethanolic extract of Emblica Officinalis (EEO) as lipid lowering and
      cardiovascular protective agent against high dietary fat supplemented to
      experimental rats. Further to study a comparative analysis between EEO and
      atorvastatin on hyperlipidemia and cardiovascular integrity. Materials and
      Methods: EEO was prepared and phytochemical analysis was done. Rats were divided
      into five groups, having six rats in each group as following; Group I-control
      (20% fat); Group II (+ EEO 100 mg/kg body wt); Group III (fed with high fat diet;
      30% fat); Group IV (fed with high fat diet; 30% fat + EEO 100 mg/kg body wt) and
      Group V (fed with high fat diet; 30% fat + atorvastatin 4 mg/kg body wt). The
      treatments were continued for 21 days. Gravimetric parameters and
      electrophysiological parameters {Heart Rate (HR), sympatho-vagal balance} were
      recorded and lipid profiles of all the groups were measured. ANOVA, correlation
      and multiple regressions were done for analysis of data. Results: Significant
      alteration in serum lipid profile was observed in rats fed with high dietary fat
      but supplementation of EEO was found to be reversible. Electrophysiological
      evaluation revealed altered HR and sympatho-vagal balance in high dietary fat fed
      rats (Group III) which indicate cardiac autonomic malfunctions which were found
      to be improved in Emblica officinalis supplemented group of rats (Group IV).
      Further, analysis has shown significant negative correlation between HDL/LDL and
      sympatho-vagal balance in all groups of rats which clearly indicate a role of
      dietary fat on sympatho-vagal balance. These results further corroborated with
      findings of histopathological study on myocardium and elastic artery. Conclusion:
      Observations from the study indicate a beneficial role of ethanolic extract of
      Emblica officinalis (amla) on dyslipidemia and cardiac autonomic functions in
      rats treated with high fat diet.

PMID- 29207699
TI  - Effect of 12 Weeks of Yoga Therapy on Quality of Life and Indian Diabetes Risk
      Score in Normotensive Indian Young Adult Prediabetics and Diabetics: Randomized
      Control Trial.
AB  - Introduction: India has become the epicentre for diabetes, a stress-related
      disorder affecting the working skills and day-to-day lifestyle management of
      younger population. Most of the studies have reported the effect of yoga on
      improving Quality of Life (QoL) in diabetic patients with other comorbidities.
      Till date, no randomized control trial reports are available to show the effect
      of yoga therapy on QoL and Indian Diabetes Risk Score (IDRS) in normotensive
      prediabetic and diabetic young individuals. Aim: To determine the effect of 12
      weeks of yoga therapy on QoL and IDRS among normotensive prediabetic and diabetic
      young Indian adults. Materials and Methods: A randomized control trial was
      conducted in Endocrinology Outpatient Department (OPD). Normotensive participants
      (n=310) aged 18-45 years were divided into healthy controls (n=62), prediabetics
      (n=124) and diabetics (n=124). Study group subjects were randomly assigned to
      Group II (n=62, prediabetes-standard treatment), Group III (n=62, prediabetes
      standard treatment + yoga therapy), Group IV (n=62, diabetes-standard treatment)
      and Group V (n=62, diabetes-standard treatment + yoga therapy). Flanagan QoL
      scale, IDRS questionnaire, Fasting Plasma Glucose (FPG) and insulin were assessed
      pre and post 12 weeks of intervention. Statistical analysis was done using
      Student's paired t-test and one-way ANOVA. Results: Pre-post intervention
      analysis showed significant improvement in QoL scale with p<0.01 in Group II and
      Group IV; p<0.001 in Group III and Group V respectively. There was significant
      reduction in IDRS in Group II (p<0.05); p<0.001 in Group III, Group IV and Group
      V respectively. Significant difference (p<0.001) in QoL scale and IDRS were found
      when study groups with standard treatment along with yoga therapy were compared
      to standard treatment alone. Conclusion: Yoga therapy along with standard
      treatment for 12 weeks improved QoL and attenuated the diabetes risk among Indian
      prediabetics and diabetics compared to standard treatment alone.

PMID- 29207700
TI  - Statistical Significance is Prerequisite in Study.

PMID- 29207701
TI  - Characterization of Vancomycin Resistant Enterococci in Hospitalized Patients and
      Role of Gut Colonization.
AB  - Introduction: Enterococci are part of the normal intestinal flora and have been
      recognized as important human pathogens. Vancomycin Resistant Enterococci (VRE)
      are global threat as this resistance is transmissible and also poses a challenge
      for infection control. Aim: This study was undertaken to study phenotypic and
      genotypic characteristics of VRE from clinically significant infections among
      hospitalized patients and their association with gut colonization. Materials and
      Methods: Clinically significant isolates of enterococci (n=250) were studied.
      Species confirmation was done by Polymerase Chain Reaction (PCR). Minimum
      Inhibitory Concentration (MIC) for vancomycin was determined by E-test. PCR for
      VanA, VanB and VanC1 gene was done for genotypic characterization. MIC for
      teicoplanin, linezolid, tigecycline, daptomycin and quinupristin-dalfopristin was
      determined by E test. Patients with VRE infection were screened for gut
      colonization using vancomycin screen agar (6 MUg/mL). Continuous data was
      analysed using the Student's t-test. Categorical data was assessed using
      Pearson's Chi-square test. A value of p <= 0.05 was considered statistically
      significant. Results: There was good correlation between the phenotypic and
      genotypic methods used for species identification and detection of vancomycin
      resistance. E. faecium (162, 64.8%) was most common followed by E. faecalis (82,
      32.84%) and E. gallinarum (6, 2.4%). Overall higher resistance was observed among
      E. faecium. Vancomycin MIC >= 2 MUg/mL was noted in 63 (25.2%) isolates. Fifty
      seven isolates showed presence of vanA and vanC1 was detected in six isolates of
      E. gallinarum. Isolates with VanB genotype was not detected in the present study.
      MIC50 (MUg/mL) for teicoplanin, linezolid, tigecycline, daptomycin and
      quinupristin-dalfopristrin was 24, 0.75, 0.064, 2 and 0.064 respectively.
      Resistance to linezolid (1, 1.6%) and tigecycline (2, 3.2%) was rare. Majority
      (33/47, 70.2%) patients with clinically significant VRE infection showed gut
      colonization. Conclusion: Vancomycin resistance among enterococci is emerging.
      Emergence of tigecycline and linezolid resistance is also posing a challenge for
      clinicians. Thus, further investigations are warranted to control vancomycin
      resistance among pathogens.

PMID- 29207702
TI  - Nagging Presence of Clostridium difficile Associated Diarrhoea in North India.
AB  - Introduction: Clostridium Difficile Associated Diarrhoea (CDAD) is a significant
      cause of morbidity in hospitalised patients worldwide. The data on clinical
      epidemiology of this disease in Indian subcontinent is scarce. Aim: To evaluate
      the risk factors and clinical course of patients with CDAD. Materials and
      Methods: A cross-sectional study was planned at our tertiary care centre, All
      India Institute of Medical Sciences, whereby, all patients who had nosocomial
      diarrhea between 2010 and 2014 were included in the study. Their clinical and
      laboratory profile were recorded using structured questionnaire and their stool
      samples were subjected to ELISA for detection of toxins A and B (Premier toxins A
      and B). Those patients who had toxins A and B in their stool samples were
      diagnosed as CDAD. The clinical and laboratory profile of CDAD patients were
      further analysed. Results: A total of 791 patients with nosocomial diarrhea were
      included in this study. CDAD was diagnosed in a total of 48(6%) patients. The
      year wise breakdown of the positive patients is as follows: 7/135 (5.2%), 4/156
      (2.6%), 5/141 (3.5%), 9/193 (4.7%) and 23/166 (13.8%), respectively. A total of
      16/48 (33.3%) of CDAD cases belonged to the age group of 51-60 years. Malignancy
      (n=15, 31.25%) was the most common underlying pathological condition. All the
      patients had a history of antibiotic intake. Most common antibiotic used in the
      patients of CDAD was third generation cephalosporins (n=27, 56.25%). The use of
      clindamycin, carbapenems and colistin increased in the year 2014. Mean duration
      of hospital stay was 9.8 days. Diarrhoea was associated with fever in 50% of the
      patients while abdominal pain was seen in 39.6% of the patients. Conclusion: The
      control of Clostridium difficile infection suffers from the rampant use of higher
      antibiotics. There is a need for proper implementation of antimicrobial
      stewardship programmes and better hospital infection control to stop the
      transmission of this nagging bug.

PMID- 29207703
TI  - Diagnosis of Acute Q Fever by Detection of Coxiella burnetii DNA using Real-Time
      PCR, Employing a Commercial Genesig Easy Kit.
AB  - Introduction: Query (Q) fever is an important zoonosis and a cause of concern for
      humans, due to the potential bioterrorism threat posed by the causative agent,
      Coxiella burnetii. Because of the danger of contracting the illness, isolation
      attempts are seldom made. Serological and molecular diagnostic tests are the main
      option. Aim: To study the prevalence of acute Q fever in Puducherry and
      surrounding districts of Tamil Nadu, India, employing a new commercial Real-Time
      Polymerase Chain Reaction (RT-PCR) kit and confirming it by the gold standard
      Immunofluorescence Assay (IFA). Materials and Methods: Acute phase blood samples
      from 72 consecutive febrile patients and 24 healthy individuals were included in
      this prospective study. DNA was extracted from the buffy coats and preserved at 
      80 degrees C. Detection of C. burnetii was carried out employing a commercial
      Real-Time PCR kit. Serum samples were tested for IgM (Phase I+II) and IgG (Phase
      I+II) by QM-120 and QG-120, Coxiella burnetii IFA Fuller Laboratories,
      California, USA. Sensitivity, Specificity, Positive Predictive Value (PPV) and
      Negative Predictive Value (NPV) were calculated keeping IFA as the reference.
      Results: Presumptive diagnosis of acute Q fever was made in two febrile patients
      by the Genesig Easy kit (2.78%). In addition to these two PCR positive cases, one
      more patient was positive for both Phase II IgM and Phase II IgG antibodies by
      the gold standard IFA. All 24 healthy controls were negative for Q fever by both
      PCR and IFA. The sensitivity, specificity, NPV and PPV for Genesig Easy kit PCR
      were: 66.67%, 100%, 100% and 98.57 % respectively against IFA as the reference.
      Conclusion: The true prevalence of Q fever in India and other developing
      countries is poorly understood, owing to the difficulties in the diagnosis of
      this infection. Since molecular diagnostic tests have good specificity and are
      mandated for confirmation of single acute samples, validation of commercial Q
      fever PCR kits is the need of the hour. Genesig Easy kit in our hands was found
      to be reliable with the moderate sensitivity and high specificity. Performing
      both PCR (with acute specimens) and IFA (with paired sera) would be ideal for Q
      fever diagnosis.

PMID- 29207704
TI  - Opportunistic Microorganisms in Oral Cavity According to Treatment Status in Head
      and Neck Cancer Patients.
AB  - Introduction: Cancer patients receiving chemotherapy and/or radiation therapy are
      prone to many predisposing factors like immunosuppression, imbalance in the oral
      flora, hypo-salivation and local tissue damage. Therefore, considered to be at
      higher risk for oral bacterial and fungal infection than the general population.
      Aim: To study oropharyngeal flora in head and neck cancer patients under
      treatment and to correlate their incidence according with Chemotherapy cycles and
      Radiochemotherapy. Materials and Methods: Total 110 patients were selected for
      study, those were further divided into two groups, group I under Chemotherapy
      (CT) - 55 patients and group II under Radiochemotherapy (RCT) - 55 patients and
      50 healthy individuals were taken as control. Saliva sample was collected from
      control and study group and inoculated on Blood agar, MacConkey agar and
      Sabouraud's Dextrose Agar (SDA). The identification of bacterial and fungal
      isolates was done by standard microbiological methods and result was calculated
      according to cycles of Chemotherapy and Radiochemotherapy combined. Significant
      differences between patients were tested using the Chi-square test or Fisher's
      exact test. A p-value less than 0.05 was considered as statistically significant.
      Result: There were 149 culture isolates from 110 patient in which Gram Negative
      Bacilli (GNB) found in 63.6%, Candida spp. in 50%, Staphylococcus aureus in 8%
      and Normal commensal of oral cavity in 13.6% patients in study group and this was
      higher than control group and this difference was statistically significant in
      relation to all isolates individually. Relatively more microorganism were
      isolated during RCT (56%) in compare to CT alone (44%), among GNB- Pseudomonas
      (27.7%,32.3%) and Klebsiella (25%,29.4%) were most frequently isolated during CT,
      RCT respectively. Candida spp. were more commonly isolated from patient on RCT
      (63.6%) than CT (36.3%) when compared to control group (20%) among which C.
      tropicalis was more prevalent species. Both GNB & Candida spp. were more commonly
      isolated in later chemotherapy cycles (CT4, CT5 CT6). Conclusion: Colonisation of
      Gram negative bacilli & Candida spp. is directly related to number of
      chemotherapy cycles and combined cancer therapy. Hence, prophylactic medication
      for these two organisms should be incorporated along with cancer therapy.

PMID- 29207705
TI  - Serum Vitamin D Level as a Risk Factor for Female Genital Tuberculosis (FGTB).
AB  - Introduction: Vitamin D is now known to be essential to Mycobacterium
      tuberculosis containment and killing through activation of 25-hydroxyvitamin-D
      receptors (VDRs) present on all immune cells or obtained from dietary food stuffs
      as either vitamin D3 or vegetable vitamin D2 (also known as ergocalciferol). Aim:
      To evaluate the association of serum vitamin D level between the Female Genital
      Tuberculosis (FGTB) cases and healthy controls. Materials and Methods: Total 120
      cases and 120 controls enrolled for the study following inclusion and exclusion
      criteria. Detailed clinical history was taken from each subjects. Total of 3 ml
      of the blood was collected in EDTA vial from each subject (case and control).
      Quantification of serum vitamin D level was measured by active human vitamin D
      ELISA kit using an ELISA reader. Statistical analysis was done using Statistical
      Package for Social Science (SPSS) version 21.0. A p-value <0.05 was considered as
      significant. Results: A total of 120 confirmed FGTB cases and 120 healthy control
      enrolled for study. Out of 120 women 97.5%, 10.0%, 3.3%, 3.3% were detected
      positive for M. tuberculosis respectively. Comparing the mean demographic value
      of age and BMI were (29.03+/-3.127, 28.03+/-3.00) and (22.92+/-3.33, 24.15+/
      3.97) respectively with the p=0.012* and p=0.010* found to be significant among
      cases and controls. The mean serum vitamin D level was 14.96+/-8.81 in cases and
      23.00+/-8.83 in controls with p-value<0.001. There was a significant positive
      association found in low serum vitamin D level among FGTB cases than controls.
      Conclusion: Vitamin D is important for normal immune cell function, as well as
      regression of FGTB disease. FGTB may be controlled by regulating the serum
      vitamin D level concentration. This study suggests that, vitamin D deficiency and
      BMI is strongly associated with the progression of active FGTB disease which
      alters the expression of antimicrobial peptide and lead to the persistence of TB
      infection. Therefore, serum vitamin D level may play an important role in
      treatment of FGTB.

PMID- 29207706
TI  - Detection of blaCTX-M Extended Spectrum Beta-lactamase Producing Salmonella
      enterica Serotype Typhi in a Tertiary Care Centre.
AB  - Introduction: Infections caused by Salmonella are an important public health
      threat in tropical and subtropical countries. Due to the emergence of resistance
      to ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole (multidrug
      resistant salmonellae) in the late 1980s, fluoroquinolones and extended spectrum
      cephalosporins became the drugs of choice. Resistance to cefotaxime and
      ceftriaxone due to the production of Extended Spectrum Beta-Lactamase (ESBL) and
      reduced susceptibility to ciprofloxacin have emerged resulting in treatment
      failure. The Cefotaximase (CTX-M) type ESBLs are the most widespread beta
      lactamase among Enterobacteriaceae including salmonellae. Aim: To detect the
      presence of blaCTX-M in salmonellae causing human infections. Detection of qnr
      genes to identify the coexistence of blaCTX-M and qnr gene. Materials and
      Methods: The study included 103 consecutive, non-repetitive salmonellae isolated
      from clinical specimens obtained from July 2015- June 2016 which were identified
      up to species level by conventional/automated methods. Susceptibility to various
      classes of antimicrobial agents was determined by disc diffusion method. Minimum
      Inhibitory Concentration (MIC) to cefotaxime and ceftriaxone was determined by
      agar dilution method. The results were interpreted in accordance with Clinical &
      Laboratory Standard Institute (CLSI) (guidelines 2015. Detection of the ESBL
      phenotype was performed by the combined disk method. Polymerase Chain Reaction
      (PCR) amplification of all isolates was performed using group specific primers to
      characterize the presence of blaCTX-M, qnrA, qnrB and qnrS. Result: Of the 103
      study isolates two isolates of Salmonella typhi were resistant to cefotaxime and
      ceftriaxone and had a MIC of 128MUg/ml. PCR amplification and sequencing detected
      the presence of blaCTX-M-15 in these two isolates. These two isolates exhibited
      resistance to ciprofloxacin in vitro but qnr gene was not detected in these
      isolates. Conclusion: Resistance to third generation cephalosporins among
      salmonellae is a cause for concern as it may lead to treatment failure. It is
      imperative to continuously monitor the susceptibility pattern as enteric fever is
      endemic in India.

PMID- 29207707
TI  - Diagnostic Approach to Viral Acute Encephalitis Syndrome (AES) in Paediatric Age
      Group: A Study from New Delhi.
AB  - Introduction: Acute Encephalitis Syndrome has heralded the emergence of multiple
      virulent pathogens, which may result in severe morbidity and mortality. In India,
      encephalitis is not notified and there has been a dearth of analysis for trends
      in encephalitis death rates and causation. A downward trend has been observed in
      encephalitis deaths, due to 'known' causes, which can be largely explained by
      improvement in diagnostic, treatment, and prevention methods. There is still a
      very high proportion of encephalitis deaths in developing countries, where the
      aetiological diagnosis of the pathogen is not established and thus, lies the
      importance of monitoring encephalitis morbidity and mortality with a view to
      improve pathogen diagnosis and identify emerging infectious diseases. Aim: To
      formulate a diagnostic approach to viral acute encephalitis syndrome in
      paediatric age group. Materials and Methods: A cross-sectional study including 50
      paediatric patients, clinically diagnosed with acute encephalitis syndrome using
      WHO criteria was conducted. The CSF of all the patients was evaluated to diagnose
      the aetiology for viral pathogens. ELISA was used for diagnosing Japanese
      encephalitis and dengue encephalitis; and multiplex real time PCR was used for
      detecting HSV-1, HSV-2, Varicella zoster virus, Mumps virus, Enterovirus and
      Parechovirus. Results: Confirmed diagnosis was established in 11 (22%) of 50
      cases. A confirmed or probable viral agent of encephalitis was found in 7 (14%),
      bacterial agent was found in 2 (4%), non-infectious aetiology was found in 2
      (4%). Fatal outcome was independently associated with patient age. Conclusion:
      Despite extensive testing, the aetiologies of more than three fourth of the cases
      remains elusive. Nevertheless the result from the present study may be useful for
      future design of early diagnosis and treatment of the disease. New strategies for
      pathogen identification and continued analysis of clinical features and case
      histories should help us improve our ability to diagnose, treat and prevent
      encephalitis.

PMID- 29207708
TI  - In Vitro Anti-Cariogenic Plaque Effects of Essential Oils Extracted from Culinary
      Herbs.
AB  - Introduction: Cariogenic bacteria including mutans streptococci and lactobacilli
      are partly but significantly involved in dental caries development. An effective
      prevention strategy against dental caries is to decrease the accumulation of this
      microbiota either in planktonic or in biofilm form. Aim: To examine the
      antimicrobial and anti-plaque effects of some culinary herbs (spices), so the
      herbs are plausibly used as alternative and effective herbal plaque control
      supplements to promote good oral health. Materials and Methods: Essential oils
      extracted from sweet basil (Ocimum basilicum), cinnamon bark (Cinnamomum
      zeylanicum), sweet fennel (Foeniculum vulgare), kaffir lime (Citrus hystrix),
      black pepper (Piper nigrum), peppermint (Mentha piperita), and spearmint (Mentha
      spicata) were primarily examined for their antimicrobial activities against the
      cariogenic bacteria (Streptococcus mutans KPSK2 and Lactobacillus casei) using
      the agar disk diffusion and broth microdilution methods, respectively. These
      essential oils were then analysed for anti-plaque effects (retardation of S.
      mutans biofilm formation and reduction of the in vitro established biofilm). This
      experimental study was performed at the Department of Oral Microbiology, Faculty
      of Dentistry, Mahidol University during June 2015 till August 2016. Results: All
      selected essential oils showed different degrees of antimicrobial activity
      against the planktonic form of both cariogenic bacteria. Cinnamon bark essential
      oil expressed the strongest inhibitory effect against S. mutans {MIC of 0.08%
      (v/v)} and L. casei {MIC of 0.16% (v/v)}, whereas the weakest effect was found in
      kaffir lime essential oil {MIC values of 2.5% and 5.0% (v/v) for S. mutans and L.
      casei, respectively}. Up to 80% of S. mutans biofilm was retarded to form on the
      substratum primed with these spice essential oils, especially cinnamon oil. The
      preventive effect of these oils was in dose- and exposure time-dependent manners.
      For reductive effect against the 24-hour pre-established S. mutans biofilm, at
      least 50% of the biofilm mass was reduced when the biofilm was treated with each
      essential oil at the MIC for an hour. The reductive effect against the in vitro
      established S. mutans biofilm of these culinary herb essential oils only depended
      on the exposure time. Conclusion: Cinnamon and sweet basil essential oils with
      impressive in vitro anti-cariogenic bacteria and anti-plaque effects may be
      proposed as alternative and effective supplements to promote oral health status.

PMID- 29207709
TI  - Isolation of the Rare Opportunistic Yeast Saprochaete capitata from Clinical
      Samples-Experience from a Tertiary Care Hospital in Southern India and a Brief
      Review of the Literature.
AB  - Introduction: Saprochaete capitata (Teleomorph: Magnusiomyces capitatus) is a
      ubiquitous yeast found in environmental sources such as soil, water, air, plants
      and dairy products. It is also a part of the normal microbial flora in humans.
      The yeast is being increasingly reported as an opportunistic pathogen, especially
      in patients in the haemato-oncology setting, the infection being often mistakenly
      diagnosed as invasive candidiasis. Aim: To review the epidemiological, clinical
      and microbiological features of six patients admitted in our hospital over a
      period of 10 years (from January 2007 to December 2016), from whom Saprochaete
      capitata was isolated. Materials and Methods: A retrospective study was conducted
      and the epidemiological, clinical, imaging and microbiological data of the six
      patients were collected and analysed. Results: The age of the six patients ranged
      from 19 years to 65 years with a median age of 53 years. There were two males and
      four females. In three out of the six patients, the isolation of S. capitata was
      considered clinically significant as the yeast was isolated repeatedly from blood
      and/or respiratory specimens and the clinical features could not be explained by
      any other alternative diagnosis. Haematological malignancy was the underlying
      disease in three out of the six patients while one patient was on triple
      immunosuppression following renal transplantation four years back. Three out of
      the six patients had severe neutropenia with Absolute Neutrophil Count (ANC) <=
      500 at the time of isolation of S. capitata. Two patients with clinical features
      of fungal sepsis received antifungal therapy with Amphotericin B but succumbed
      within a short period of starting the therapy. The post renal transplant patient
      who presented with pneumonia recovered after treatment with a combination of
      Amphotericin B and Voriconazole. Conclusion: Awareness regarding the
      epidemiological, clinical and microbiological aspects of invasive infections
      caused by S. capitata is essential for early recognition and appropriate
      management.

PMID- 29207711
TI  - Universal Presence of blaNDM-1 Gene in Carbapenem-Resistant Gram-Negative Bacilli
      in an Indian Hospital in 2015.

PMID- 29207710
TI  - A Case of Keratomycosis Caused by Fusarium Solani at Rural Tertiary Care Center.
AB  - Keratomycosis is defined as invasive infection of corneal stroma caused by
      variety of fungi. Most of these cases occur in agricultural workers with history
      of corneal trauma with vegetative matter contaminated by fungi. Fusarium species
      which causes keratomycosis receives occasional mention in literature. We report a
      case of a 27-year-old male, farmer by occupation presented with complains of
      foreign body sensation, itching and discharge from the right eye and developed
      white patch on cornea which was progressed gradually to size of diameter of pea
      which was later diagnosed as keratitis caused by Fusarium species.

PMID- 29207712
TI  - Role of HER-2/neu in Premalignant and Malignant Lesions of Uterine Cervix.
AB  - Introduction: In light of literature and controversy that exists in various
      cervical lesions, this prospective study was designed to explore the expression
      of Human Epidermal Growth Factor Receptor-2 (HER-2/neu) in the cervical lesions
      and its correlation with the histopathological grade and type of tumour.
      Immunohistochemistry (IHC) was performed to evaluate HER-2/neu expression as it
      is the most reliable method of detecting overexpression of HER-2/neu. Aim: To
      assess the role of HER-2/neu expression in premalignant and malignant lesions of
      uterine cervix. Materials and Methods: Seventy cases of premalignant and
      malignant cervical lesions received in our department from January 2015 to
      December 2016, were included in study and Polyclonal Rabbit Anti-Human c-erbB-2
      oncoprotein from DAKO was used. Standard streptovidin-biotin peroxidase method of
      IHC was followed. A golden brown membrane and cytoplasmic staining was taken as a
      positive reaction and intensity of expression was graded according to the 2014
      ASCO/CAP guidelines for HER-2/neu reporting. Results: Out of total 70 cases, HER
      2/neu expression scores were 0 in 64.3% {23 cases of Cervical Intraepithelial
      Neoplasia (CIN) and 22 of Squamous Cell Carcinoma (SCC)}, +1 in 22.9%, (04 cases
      of CIN and 12 of SCC) +2 in 10% (06 cases of SCC and 01 of adenosquamous
      carcinoma) and +3 in 2.9% (02 cases of adenocarcinoma) cases. HER-2/neu
      overexpression rate was significantly higher in malignant (48.8%) as compared to
      pre malignant (14.8%) cases (p=0.004) and expression scores were higher (+2 and
      +3) in 20.9% of malignant cases as compared to none of pre malignant cases
      (p=0.020). Significant higher HER-2/neu scores are seen (+2 and +3) in all the
      adenocarcinoma cases as compared to 15% cases of SCC (p<0.001). Among malignant
      cases, HER-2/neu expression was statistically significantly higher in {Moderately
      Differentiated (MD) + Poorly Differentiated (PD)} 59.09% as compared to {Well
      Differentiated (WD)} 38.09% cases (p=0.090). Conclusion: Study shows that
      expression of HER-2/neu is relatively lower in cervical lesions. However, the
      results of our study show that with shift from well to poorly differentiated
      lesions; the HER-2/neu expression rate shows an incremental trend.

PMID- 29207713
TI  - Analysis of Patient's Satisfaction with Phlebotomy Services in NABH Accredited
      Neuropsychiatric Hospital: An Effective Tool for Improvement.
AB  - Introduction: Patient's satisfaction is the need of the hour and one of the most
      important quality indicators in the laboratory medicine. Aim: To assess the
      patient's satisfaction with phlebotomy services in a neuropsychiatric hospital by
      a structured questionnaire with grading scale. Also, identify the problems
      causing dissatisfactions and to undertake necessary Corrective and Preventative
      Action (CAPA). Materials and Methods: Total 1200 patients were randomly selected
      over a period of two months (June and July 2016). A structured self designed
      questionnaire (feedback form) was devised in both Hindi and English languages
      containing ten questions with a grading scale for each question. It also included
      suggestions from the users. All the selected patients or their attendants filled
      up this questionnaire. At the same time, they were also interviewed by phlebotomy
      staff. A statistical analysis was conducted using SPSS version 16.0 software and
      Likert scale. Results: A total of 94% of the patients were satisfied with the
      phlebotomy services. Almost 30.0% patients found the phlebotomy services to be
      very good, but the majority of them (40.5%) found it to be good and another 23.5%
      found it to be satisfactory while, 4% found the services to be poor and 2% found
      it to be very poor. The highest rate of satisfaction (4.21) was noted in case of
      parameter-ease to find collection sample room and lowest rate of satisfaction
      (3.92) was scored by the parameter-staff's wearing proper uniform. Depending upon
      the deficient areas some corrective actions were suggested such as strict
      compliance of personal protective equipments, regular training to improve
      technical skill, knowledge and behaviour with emphasis on cleanliness of work
      area. Conclusion: Even though the overall patient's satisfaction was high, there
      were areas which needed our attention such as waiting time for phlebotomy
      procedure, lack of proper sitting arrangement, techniques of sample collection,
      knowledge of universal precautions etc. Appropriate corrective and preventive
      actions were taken to solve the problems. Thereby, feedback proved effective in
      maintenance and improvement of phlebotomy services.

PMID- 29207714
TI  - Paediatric Peripheral Primitive Neuroectodermal Tumour - A Clinico-Pathological
      Study from Southern India.
AB  - Introduction: Primitive Neuroectodermal Tumour (PNET)/Ewing Sarcomas (ES) are
      aggressive childhood malignancies with neuroectodermal differentiation. Aim: To
      study the clinical presentation, morphology, Immun-ohistochemistry (IHC),
      management and outcome of all the cases of paediatric pPNET/ES reported in our
      tertiary care centre over a period of six years. Materials and Methods: This was
      a retrospective study conducted at Sri Ramachandra Medical College and Research
      Institute, Chennai, India. All biopsy proven cases of peripheral PNET/ES, in
      patients less than 18 years of age for a period of six years were included in
      this study. The corresponding clinical details regarding initial presentation,
      treatment and follow up were retrieved from the case files and analysed. Survival
      rate was calculated and Kaplan-Meier survival curve was plotted. Results: We
      describe eleven cases of paediatric peripheral PNET/ES. The mean age at
      presentation was 94.08 (+/-58.27) months with a male/female ratio of 1.2:1. About
      27.3% cases, all male with a mean age of 140 months at presentation, had distant
      metastasis during initial diagnosis. Biopsy showed small round blue cell
      morphology on light microscopy. IHC revealed strong membranous staining for CD99
      in all cases. All children were treated with neo-adjuvant chemotherapy and then
      surgery, followed by radiotherapy if indicated. The cases were followed up for a
      mean duration of 20.82 months (ranging from one to 66 months). Nine children are
      doing well on follow up (81.8% survival rate). Two cases with metastasis at
      initial presentation died. Patients with metastatic disease exhibited a mean
      duration of survival of 9.66 (+/-7.24) months and those with localized disease
      exhibited a mean duration of survival of 25 (+/-22.88) months. Conclusion:
      Metastasis at diagnosis is the single most important factor affecting prognosis.
      This was reflected in the present study where cases with metastasis exhibited a
      short mean duration of survival when compared to localized disease. It is likely
      that many cases of PNET/ES were not accurately identified in the past as IHC
      plays a vital role in the diagnosis of these small round blue cell tumours. IHC
      in adjunct with molecular studies has improved diagnostic accuracy.
      Multidisciplinary management and good supportive care when the lesion is
      localized has lead to improved survival.

PMID- 29207715
TI  - A Correlative Study between Platelet Count, Mean Platelet Volume and Red Cell
      Distribution Width with the Disease Severity Index in Psoriasis Patients.
AB  - Introduction: Platelet activation is presumed to play an important role in the
      immunoinflammatory reactions. Several recent studies on a variety of inflammatory
      disorders have used Mean Platelet Volume (MPV) as a marker for platelet
      activation. Aim: To determine the relationship between haematological parameters
      and disease severity index in psoriasis patients. Materials and Methods: A Case
      control study was carried out on 50 psoriatic patients and 50 healthy control
      subjects. Ten haematologic parameters were compared between patients and control
      subjects. These parameters were also correlated in patients with PASI (Psoriasis
      Area and Severity Index) score. The data was statistically analysed using IBM
      SPSS software (Version 21). Spearman Rank Correlation was used to find the
      correlation between PASI and haematological parameters. Results: When all the
      patients were considered together, mean values for MPV, Platelet Count (PLT) and
      Red Cell Distribution Width (RDW) were significantly different between the two
      groups (Control and Patients). While MPV and RDW were raised, PLT was reduced in
      patients of both sexes when compared with controls. In Male patients the MPV and
      RDW showed statistically significant correlation with Psoriasis Area And Severity
      Index (PASI) (MPV <0.01; RDW<0.05), whereas PLT though reduced in both sexes when
      compared with controls, it showed significance in female patients alone (p
      <0.01). Conclusion: The mean values for MPV and RDW were higher and mean platelet
      values were lower in patients than controls. The MPV values in male patients and
      Platelet counts in female patients showed strong positive and negative
      correlation respectively with the PASI score. It can be concluded that rising MPV
      and decreasing PLT could be good indicators of disease severity and progression.
      These indicators could also help in assessing the treatment course of the
      disease.

PMID- 29207716
TI  - Expression of p16INK4A Protein in Cervical Intraepithelial Neoplasia and Invasive
      Carcinoma of Uterine Cervix.
AB  - Introduction: Cervical cancer still ranks as the most frequent cancer among women
      in India. Infection with Human Papilloma Virus (HPV) results in precancerous
      lesions and invasive cervical cancer. Interaction of HPV oncogenic proteins with
      cellular regulatory proteins leads to upregulation of p16INK4A, a cyclin
      dependent kinase inhibitor. Therefore, p16INK4A overexpression is a surrogate
      biomarker of HPV infection making it useful in evaluating HPV associated
      premalignant and malignant lesions of gynaecological tract. Aim: This study was
      conducted to evaluate the usefulness of p16INK4A as a biomarker in dysplastic and
      malignant alteration of cervical epithelium.Materials and Methods: A total of 57
      specimens diagnosed histopathologically as cervical dysplasia or malignancy were
      included in this prospective study of two year duration. Immunohistochemical
      (IHC) study of p16INK4A expression was performed on normal cervical tissue
      samples, Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, CIN 3, squamous cell
      carcinoma, adenocarcinoma. Expression was scored by two methods. One was simple
      positive versus negative p16INK4A staining and the other method was a semi
      quantitative IHC scoring (0 to 8 points) according to the intensity of staining
      and the proportion of stained cells. The collected data was entered in excel
      sheet and analysed using Statistical Package For Social Science (SPSS) 16.0
      software and the descriptive statistics, Chi-square test. The p-value of <0.05
      was considered statistically significant. Results: Nuclear and/or cytoplasmic
      p16INK4A immunoreactivity was absent in normal cervical tissue, while
      immunopositivity was 25% in CIN 1, 50% in CIN 2, 75% in CIN 3, 75% and 100% in
      squamous cell carcinoma and adenocarcinoma respectively. All normal cervical
      samples had low scores (0 to 2 points), while number of cases with high scores
      was proportional to the degree of cervical dysplasia or invasive carcinoma.
      p16INK4A immunostaining with higher expression (score>5) was observed in 75%
      cases of carcinoma cervix. Conclusion: IHC expression of p16INK4A is related to
      degree of histological dysplasia and malignancy, suggesting its prognostic and
      predictive value in the management of cervical cancers.

PMID- 29207717
TI  - Heterotopic Prostate at Autopsy- An Unusual Mass at the Dome of the Urinary
      Bladder.
AB  - Heterotopic prostate in the dome of the urinary bladder is extremely rare and
      difficult to diagnose. It is often mistaken for neoplastic masses and
      histopathological examination is warranted for diagnosis. We report an autopsy
      case of an ectopic prostate at the dome of the bladder which mimicked a neoplasm
      on gross pathology.

PMID- 29207718
TI  - An Alpha Fetoprotein Producing Gastric Tumor with Yolk Sac, Hepatoid and
      Papillary Adenocarcinoma Components.
AB  - Alpha Fetoprotein (AFP) producing gastric carcinomas are very rare and have
      unique clinicopathological features and an extremely poor prognosis. Here, we
      report a case of AFP producing gastric carcinoma with three distinct
      histomorphologic patterns such as yolk sac like, hepatoid, tubular and papillary
      adenocarcinoma components. The uniqueness of this case is absence of metastases
      and associated findings such as fundic gland polyposis with varying degrees of
      dysplasia, gastric and duodenal well differentiated neuroendocrine tumour and
      rectal ganglioneuroma. The patient is symptom free as of two and half year's
      postoperative period. AFP producing gastric tumours although rare, need to be
      identified as it is known to carry poor prognosis.

PMID- 29207719
TI  - Approach to a Pregnant Woman with Anti D + Anti C Reactivity Pattern: A
      Diagnostic Conundrum.
AB  - The Rhesus G antigen is present on all RBCs that are C+ and also on most D+ RBCs.
      Due to this co-distribution of G with either C or D antigen, it mimics a
      reactivity pattern of anti C + anti D on Indirect Antiglobulin Test (IAT), though
      the role of Anti G in causing Hemolytic Disease of Newborn (HDN) is
      controversial. The differentiation of anti D, anti C, and anti G is essential
      particularly in pregnant females. We hereby report a rare case of anti G with
      anti D and anti C in a pregnant woman with emphasis on approach to identify anti
      D+C+G and its implications.

PMID- 29207720
TI  - Locally Aggressive Primary Intraosseous Paraganglioma of Sacrum.
AB  - Primary Intraosseous Paraganglioma (PGL) of sacrum is highly uncommon. Few of the
      spinal PGL reported were mostly intradural mass. Paraganglionic tissue is usually
      not present in the bone. So far, only seven cases of primary intraosseous sacral
      PGL have been reported in the literature. There are no dependable prognostic
      histological features to differentiate benign from malignant PGL. The only
      unequivocal criterion for malignancy is metastasis to an organ where
      paraganglionic tissue is normally not present. However, an aggressive nature can
      be identified histologically by loss of architecture, decreased or absent
      sustentacular cells and Ki-67 index of >3%. We report a case of an elderly male
      who was admitted with complaints of swelling in the lower back with associated
      radiating pain and difficulty in sitting of two months duration. A diagnosis of
      sacral chordoma was made on Magnetic Resonance Imaging (MRI). No other mass was
      detected elsewhere in his body. The patient underwent surgical excision followed
      by radiotherapy. On histopathology and immunohistochemistry, a diagnosis of
      locally aggressive primary intraosseous PGL of sacrum was rendered. Hence, when
      evaluating a lytic sacral mass, PGL has to be considered as a differential
      diagnosis.

PMID- 29207721
TI  - Anorectal Melanoma: An Unusual Cause of Rectal Bleeding.
AB  - Anorectum is a rare site for primary melanoma. It is an aggressive cancer with
      poor prognosis. The diagnosis is often delayed due to non-specific signs and
      symptoms. Clinically, it is often misdiagnosed as hemorrhoids. The cytological
      diagnosis can be challenging especially when melanin pigment is sparse or absent.
      Herein, we present a rare case of anorectal melanoma which was initially
      misdiagnosed as hemorrhoids. A final correct diagnosis was made on cytology when
      later on the patient developed inguinal metastasis.

PMID- 29207722
TI  - Thalassaemia Trait with Gaucher Disease: A Diagnostic Dilemma.
AB  - Gaucher Disease is an autosomal recessive disease caused by the accumulation of
      glucocerebrosidase due to deficiency in lysosomal glucocerebrosidase.
      Thalassaemia trait is asymptomatic and is usually an incidental diagnosis. Both
      thalassaemia and Gaucher disease can have similar haematologic manifestations and
      hence, their coexistence causes diagnostic dilemma. Our patient presented at one
      and-a-half years with weakness, pallor, failure to thrive and massive
      hepatosplenomegaly. Clinical examination and history pointed to a lipid storage
      disease. Peripheral smear revealed microcytic hypochromic cells and nucleated red
      cells with haemolytic blood picture. Thalassaemia trait was indicated on
      haemoglobin variant analysis using High Performance Liquid Chromatography. Liver
      biopsy, bone marrow aspirate and therapeutic splenectomy revealed Gaucher-like
      cells. Type 1 Gaucher disease can be clinically asymptomatic as well as present
      with massive liver and spleen enlargement and involvement of bone marrow.
      Anaemia, splenomegaly and thrombocytopenia are the usual presentations at
      diagnosis, similar to the haemoglobinopathies. Gaucher-like cells with normal
      beta-glucocerebrosidase (pseudo-Gaucher cells) are seen in thalassaemia,
      leukaemia, mycobacterial infections and myeloma. Gaucher disease coexisting with
      thalassaemia trait is uncommon. We report the occurrence of thalassaemia trait
      and Gaucher disease in a child, which resulted in confusion regarding the
      haematological diagnosis. This report highlights the necessity of independent
      establishment of the diagnosis in every patient so that appropriate management
      decisions are taken.

PMID- 29207723
TI  - Papillary Renal Cell Carcinoma with Tubercular Paraaortic Lymphadenopathy: A
      Blessing in Disguise.
AB  - Incidental Renal Cell Carcinoma (RCC) can be found in a tubercular kidney;
      however, the vice versa i.e., finding tubercular lymphadenopathy after radical
      nephrectomy for cancer is exceptionally rare. To the best of our knowledge, only
      two cases of coexistent renal cell carcinoma and tubercular paraaortic
      lymphadenopathy have been reported till date. Out of these, only one case was of
      papillary renal cell carcinoma. We hereby, report a rare case of papillary renal
      cell carcinoma with coexisting paraaortic tubercular lymphadenopathy, which was
      upstaged based on radiology findings. This case highlights the importance of
      considering the possibility of tuberculosis in cancer-associated lymphadenopathy.
      This can prevent unnecessary lymphnode dissection and inappropriate clinical
      upstaging in renal cancer patients.

PMID- 29207724
TI  - Diagnosis of Lafora Disease by Skin Biopsy.

PMID- 29207725
TI  - Rapid and Accurate Diagnosis of Acute Pyogenic Meningitis Due to Streptococcus
      Pneumoniae, Haemophilus influenzae Type b and Neisseria meningitidis Using A
      Multiplex PCR Assay.
AB  - Introduction: Acute bacterial meningitis is one of the major causes of morbidity
      and mortality in children and geriatric population, especially in developing
      countries. Methods of identification are standard culture and other phenotypic
      tests in many resource poor settings. Aim: To use molecular methods for the
      improvement of aetiological diagnosis of acute pyogenic meningitis in patients.
      Materials and Methods: CSF samples of 125 patients were included for the study.
      Gram staining and culture were performed according to standard procedures.
      Antigen was detected using commercial latex agglutination test kit. Multiplex PCR
      was performed using previously published primers and protocols. Fischer's exact
      test was used for finding association between presence of the disease and
      clinical/biochemical parameters, considering two tailed p<0.05 as statistically
      significant. Sensitivity, specificity, positive and negative predictive values
      were calculated using Graphpad QuicCalc software. Results: A total of 39 cases
      (31.2%) were confirmed to be of acute pyogenic meningitis based on biochemical
      methods. Only 10/39 was positive for the three organisms tested. Multiplex PCR
      was able to detect one additional isolate each of Streptococcus pneumoniae and
      Haemophilus influenzae type b. When compared with multiplex PCR as the gold
      standard, culture and latex agglutination tests had same sensitivity (80%),
      specificity (100%), PPV (100%) and NPV (97.8%), whereas Gram stain had poor
      sensitivity (40%) and good specificity (95.6%). Detection rates were higher in
      multiplex PCR for the two organisms Streptococcus pneumoniae and Haemophilus
      influenzae type b. Conclusion: Multiplex PCR was more sensitive than culture or
      antigen detection, and employing this assay can significantly increase the speed
      and accuracy of identification of the pathogen.

PMID- 29207726
TI  - Pleiotropic Effects of Losartan in Hypertensive Patients with Dyslipidemia.
AB  - Introduction: In essential hypertension, the comorbidity of dyslipidemia is very
      common. In addition to hypertension, dyslipidemia is linked to cardiovascular
      disease, stroke and decline in renal function. Unlike other angiotensin receptor
      blockers, Losartan has been claimed to have unique pleiotropic property and
      thereby decreasing the risk of future cardiovascular complications. Aim: The
      present study was done to assess on the pleiotropic effect of losartan in newly
      diagnosed hypertensive patients with dyslipidemia. Materials and Methods: Fifty
      four hypertensive patients with dyslipidemia who fulfilled the eligible criteria
      and were willing to give informed consent were included in the study after
      getting Institutional Ethical Committee (IEC) approval. All the study
      participants were given tab. Losartan 50mg once daily for four weeks. At the end
      of 1st, 2nd, 3rd and 4th week, blood pressure control and compliance were
      monitored. At the end of 4th week all the baseline laboratory parameters like
      renal function test, liver function test, lipid prolife and random blood sugar
      were performed. The EQ-5D questionnaires were completed at two points during the
      study: at the patient's initial visit before enrollment in the study and after 4
      weeks of Losartan therapy. Appropriate statistical methods were used to analyse
      the results.The primary endpoint was reduction in blood pressure and improvement
      in lipid profile and improvement in quality of life score from baseline after 4
      weeks of losartan therapy. Results: Four patients were withdrawn due to non
      compliance and totally 50 patients completed the study. The mean systolic blood
      pressure was reduced from 154.54 mm Hg to 138.16 mm Hg with p<0.0001 and the mean
      diastolic blood pressure was reduced from 91.56 mm Hg to 82.44 mm Hg with
      p<0.0001. There was a significant reduction in the mean total cholesterol from
      189.52 to 180.46 mg/dl, mean LDL from 110.50 to 101.32 mg/dl and mean
      triglygeride from 135.68 to 127.70 mg/dl with p<0.0001. Improvements in anxiety
      and depression, as well as other dimensions in the QOL questionnaire, paralleled
      with improvement of the clinical picture. Conclusion: Based on the results of
      this study, Losartan is safe and effective in treating hypertensive patients with
      dyslipidemia in addition to its antihypertensive effect and it also has benefits
      of reducing serum glucose, lipid levels; and improvement in the quality of life.

PMID- 29207727
TI  - Effect of Cellular Mobile Phone Use and Cetrizine on Hand-Eye Coordination and
      Visual Acuity.
AB  - Introduction: Cellular mobile phones are a major cause of distraction especially
      while driving. The aggressive and inappropriate use of cellular mobile phones has
      increased the risk of accidents. Similar alerts are available in literature for
      certain substances and drugs (e.g. second generation anti H1 drug -Cetirizine)
      which also derange psychomotor performance and parameters of alertness. Aim: This
      study measured variations in hand-eye coordination and visual acuity due to use
      of cellular mobile phone in comparison to that of commonly used antihistaminic
      drug viz., single dose Cetirizine 10 mg. Materials and Methods: It was a single
      blind, single dose, interventional study, 100 healthy human volunteers divided
      into two groups. Baseline readings of all volunteers were noted. Group-I (n=50)
      was Cetirizine group (10mg orally stat), Group -II (n=50) Cellular mobile phone
      user group. Alertness was tested on hand- steadiness tester (Reaction Time Index
      = RTI) and on Flicker-fusion apparatus (visual acuity - Critical Flicker Fusion
      Frequency per second= CFFF/sec). Baseline readings of all volunteers were noted
      before intervention. Baseline was compared with readings at three hour post
      intervention and was analysed by paired t-test. Inter-group comparison of
      parameters was also done and was analysed by unpaired t-test. Results: The
      baseline RTI (95.46+/-41.74, 85.11+/-39.05) and CFF low and high (40.07+/-9.970,
      40.76+/-9.309 and 40.42+/-9.035, 40.48+/-9.863) respectively, in Cetirizine group
      and Mobile user group were comparable. The RTI increased significantly (116.4+/
      51.46, 102.8+/-49.26) in both the groups after intervention. However, there is no
      significant change in CFF intensity from baseline in either group post
      intervention. Conclusion: Concurrent use of mobile phone while performing tasks,
      showed significant impairment of hand-steadiness which was comparable to that
      produced by single dose Cetirizine 10 mg and this may be one of the factors
      contributing to their close association with road traffic accidents.

PMID- 29207728
TI  - The Effect of Soy Isoflavones on the Menopause Rating Scale Scoring in
      Perimenopausal and Postmenopausal Women: A Pilot Study.
AB  - Introduction: Menopause is associated with many unpleasant symptoms which vary in
      different phases of menopausal transition. Although, Hormone Replacement Therapy
      (HRT) is considered the most effective mode of treatment for these symptoms, its
      use is associated with increased risk of breast cancer, endometrial cancer and
      thromboembolic events. Soy isoflavones are being widely used as a safer
      alternative to HRT, even though scientific evidence of their efficacy is poor or
      lacking. Aim: To study the effect of soy isoflavone supplementation on the
      menopausal symptoms in perimenopausal and postmenopausal women. Materials and
      Methods: An observational pilot study was done involving 29 perimenopausal and 21
      postmenopausal women prescribed 100 mg soy isoflavones for 12 weeks. Menopause
      Rating Scale (MRS) questionnaire was administered to the patients before starting
      soy isoflavone therapy and at the end of treatment. Responses were analysed using
      Statistical Package for Social Sciences (SPSS) software 23.0. Results: Total
      score of both the groups were comparable at baseline. Among perimenopausal women
      highest score was given to symptoms of psychological domain. Urogenital symptoms
      were the worst among postmenopausal women. After 12 weeks of treatment, total
      scores improved significantly by 19.55% and 12.62% in the perimenopausal and
      postmenopausal women respectively. The greatest improvement was seen in scores of
      hot flashes for both the groups and the least improvement was shown by symptoms
      of urogenital subscale. Conclusion: Soy isoflavone improves the MRS score among
      both the perimenopausal and postmenopausal women. As they are most effective for
      somatic and psychological symptoms, their use could be beneficial during
      perimenopause.

PMID- 29207729
TI  - Comparison of Different Dosing Protocols of Anti-Snake Venom (ASV) in Snake Bite
      Cases.
AB  - Introduction: Considering the cost of Anti-Snake Venom (ASV) and irregularity in
      its supply, there is often a need to curtail doses of ASV, despite guidelines for
      management of snake bite. During June 2013 to September 2013, when ASV was in
      short supply, our institutional committee reviewed the overall hospital
      statistics of snake bite cases as well as scientific literature and formulated a
      working modified protocol that used low dose of ASV in snake bite cases. Aim: To
      retrospectively analyse and compare the modified ASV protocol versus conventional
      ASV protocol with respect to outcome, number of ASV vials required, duration of
      stay in the hospital/ ICU, and additional supportive interventions needed.
      Materials and Methods: This was a retrospective study conducted at a tertiary
      care teaching hospital, Maharashtra, India. Hospital records of inpatients
      admitted for snake bite during June 2013 to September 2013 (since introduction of
      the modified protocol) as well as during June 2012 to September 2012, (when
      patients received conventional protocol-historical controls) were retrospectively
      analysed to assess the number of ASV vials received by the patients during the
      stay, need for supportive therapy, duration of stay and outcome of the patients.
      Results: There was a significant reduction in average number of ASV vials per
      patient, required vide the modified protocol compared to their historical
      controls (10.74+/-0.95 vs 28.17+/-2.75 p<0.001). There was no significant
      difference in outcome, need for dialysis, fresh frozen plasma requirement, need
      for ICU stay and duration of hospitalization of snake bite patients. Yet, the
      average cost of management of each patient reduced by approximately 11974.41 INR
      per treated patient, based on the requirement of ASV. Conclusion: The modified
      ASV protocol used in this study is more cost effective as compared to the
      conventional protocol, deserves prospective evaluation and may be followed at
      least during prime time of scarcity of ASV.

PMID- 29207730
TI  - Safety Assessment of Human Bone Marrow-derived Mesenchymal Stromal Cells
      Transplantation in Wistar Rats.
AB  - Introduction: Bone Marrow-derived Mesenchymal Stromal Cells (BM-MSCs) are
      multipotent stem cells isolated from adult human bone marrow. Properties of MSCs
      make them potentially ideal candidates for regenerative medicine. The preclinical
      data available in the literature regarding the safety assessment of MSCs at
      different dosage group is scanty. Aim: To evaluate the safety of BM-MSCs
      transplantation in Wistar rats. Materials and Methods: Eighteen adult female
      Wistar rats were used in the study. They were randomly divided into normal
      control, low dose MSCs and high dose MSCs groups. Low dose group received 3.25
      million BM-MSCs/kg body weight; high dose group received 9.75 million BM-MSCs/kg
      body weight intravenously. Body weight, food and water intake of each rat were
      measured statistically using SPSS version 16.0; animals were observed for changes
      in behaviour, general clinical signs, presence of any abnormal response,
      mortality for thirty days. Results: Repeated measures ANOVA indicated a
      significant increase in body weight, food, and water intake of all animals at all
      weeks of the study period compared to week zero (p<0.05). Between the low dose
      and high dose MSCs group, increase in absolute body weight was seen at the end of
      the 30th day which was statistically significant (p=0.01). There was no
      significant difference in body weights, food and water intake in MSCs group when
      compared to normal control. All the animals survived for the entire duration of
      the study. Further, there was no change in the behaviour of the animals, no
      adverse clinical signs or complications following the MSCs treatment. Conclusion:
      Results indicate that administration of BM-MSCs is safe when given by a slow
      intravenous infusion as it did not alter the food and water intake behaviour of
      the animals and did not have any negative effect on its body weight.

PMID- 29207731
TI  - Sodium Valproate Induced Alopecia: A Case Series.
AB  - Drug induced alopecia may range from a barely detectable shedding to an
      irreversible baldness. Alopecia associated with valproate is a dose-dependent and
      reversible side effect. We hereby report, three cases of alopecia that occurred
      in patients who received sodium valproate for various neurological conditions. In
      all three cases, long term exposure of valproate therapy led to the development
      of alopecia which eventually resolved after dose reduction or discontinuation.
      The Naranjo's causality assessment scale indicated valproate as the probable
      cause of the alopecia in all our patients.

PMID- 29207732
TI  - Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.
AB  - Introduction: MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that
      can modulate gene expression and are aberrantly expressed in many diseases,
      including cancer. It has been suggested that, the presence of single nucleotide
      polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing,
      expression and binding to target mRNA and represents another type of genetic
      variability, that can contribute to the susceptibility of human cancers. Aim: The
      present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2
      rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for
      their role in cervical cancer susceptibility. Materials and Methods: The study
      comprised 164 controls and 184 patients of cervical cancer. The genotypic
      frequency of miRNA polymorphisms were determined by using a polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic
      regression was used for statistical analysis using SPSS Software version 15.0.
      Results: Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically
      significant association with considerable risk for cervical cancer at genotypes
      (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and
      miRNA 196a2 polymorphisms showed no association with cervical cancer. However,
      interaction of miRNA polymorphisms with smoking habit showed higher risk of
      cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no
      significant modification in the risk of cervical cancer was seen for other
      polymorphisms. Conclusion: The results of the present study demonstrate that,
      miRNA 499 T/C polymorphism is significantly associated with genetic
      susceptibility to cervical cancer and may have a role in its pathogenesis.

PMID- 29207733
TI  - The Association between Prolonged Jaundice and TATA Box Dinucleotide Repeats in
      Gilbert's Syndrome.
AB  - Introduction: Jaundice is a common condition during the neonatal period.
      Prolonged jaundice occurs in a large number of breastfed infants, considering the
      impact of genetic factors on the incidence of jaundice. Aim: To determine the
      association between prolonged jaundice and TATA box dinucleotide repeats in
      Gilbert's Syndrome (GS). Materials and Methods: In this case-control study, the
      case group consisted of 51 neonates with jaundice, aged more than two weeks with
      indirect bilirubin level higher than 10 mg/dl. Acute diseases, mother's use of
      phenobarbital and other medications were the exclusion criteria. The control
      group consisted of 54 newborns without jaundice. The two groups were matched in
      terms of age and sex. TATA box polymorphisms in the promoter region of UGT1A1
      gene were evaluated using Polymerase Chain Reaction (PCR) in order to determine
      TATA box dinucleotide repeats. Results: Overall, 64.7% and 50% of subjects in the
      case and control groups were male, respectively (p=0.168). The mean age of
      neonates in the case and control groups was 20.1+/-7.1days and 18.8+/-4.1 days,
      respectively. The distribution of Gilbert genome was not significantly different
      between the two groups. In the case group, 13.7% of the subjects were homozygous,
      37.3% were heterozygous and 49% were normal. In the control group, 7.4% of the
      participants were homozygous, 35.2% were heterozygous and 57.4% were normal.
      Conclusion: The results of this study showed an association between TATA box
      polymorphism and prolonged jaundice in neonates which revealed that TATA box
      polymorphism is an important risk to increase and extend icterus.

PMID- 29207734
TI  - Prenatal Screening for Rare Co-Inheritance of HbE and beta-Thalassaemia Traits in
      Western India.
AB  - The mutations in Haemoglobin Beta (HBB) gene, bring about less or no production
      of Hb beta-chain synthesis in affected cases, leading from minor to major types
      depending on haematological indices. In compound heterozygotic conditions, two
      traits are involved, in which one parent has HbE trait and the other has beta
      thalassaemia carrier (trait). Here, we report a family of Rajasthan, West India
      which had a proband (son) having HbE/ beta-thalassaemia a co-inherited compound
      heterozygosity as revealed by DNA sequencing. It also contained upper levels of
      HbE with altered Hb and red cell indices showing asymptomatic to symptomatic
      state requiring blood transfusion periodically. The parents and Chorionic Villus
      Sampling (CVS) were HbE and beta-thalassaemia traits only. Such case is rare in
      Western India and we recommend this family for genetic counseling and genetic
      testing before they want reproductive choices in future for better management in
      a society.

PMID- 29207735
TI  - Pattern of Isolated Fatal Mechanical Injury in Homicidal Deaths: A Cross
      Sectional Study.
AB  - Introduction: Homicide is the death of one human being as a result of conduct of
      another. Multiple assaults on the body are seen in 70% cases, which indicate
      determination on the part of the accused to end the life of the victim. Aim: To
      identify the pattern, distribution and means of inflicting fatal isolated
      mechanical injury on the body in cases of homicide. Materials and Methods: This
      cross-sectional study was conducted on total 728 homicide deaths, out of which 63
      cases had an isolated fatal mechanical injury over the body and the rest 665
      cases had multiple injuries. The data collected from the study sample were
      recorded in a case record form and was analysed using Graphpad Prism 5.0.
      Results: Homicidal deaths occurring due to an isolated bodily injury were 8.65%.
      Most of the victims (82%) were males. Those in the age group more than 60 years
      and less than 10 years together constituted 38% of the cases having isolated
      fatal homicidal injury. Sharp cutting weapons were used in most of the cases
      (46.03%) followed by use of hard and blunt weapon in 20.63%. The most common site
      of isolated injury causing homicide was head (41.26%) followed by the neck in
      31.74%. The least common site of injury was the groin/scrotum (7.93%). The
      leading mode of death was coma (38.09%) followed by haemorrhagic shock in 34.92%.
      Conclusion: Victims of homicidal deaths with isolated bodily injury showed a
      distinct pattern in comparison to deaths due to homicide with multiple injuries,
      which can be an indicator of the degree of aggression, magnitude of violence and
      the determination or intention of the assailant to kill.

PMID- 29207736
TI  - Awareness of Patients' Rights among Inpatients of a Tertiary Care Teaching
      Hospital- A Cross-sectional Study.
AB  - Introduction: The rights of a patient are a set of rules of conduct which govern
      the interaction between the patients' and healthcare professionals. Every patient
      has a right to be informed about their rights and also the responsibility of the
      healthcare provider. Aim: To assess awareness among inpatient about patients'
      rights at an academic accredited hospital. Materials and Methods: A questionnaire
      based cross-sectional study was carried out among 350 patients admitted to the
      wards of a Tertiary Care Teaching Hospital. A 21-point questionnaire was
      developed based on standards of the National Accreditation Board for Hospitals
      and Healthcare Providers (NABH) and patients' charter of rights and validated.
      This charter of rights is also displayed in the hospital for patient's awareness.
      Frequencies and percentages were depicted. Chi-square test was used for
      statistical analysis. Results: Positive awareness among the patients ranged from
      28% to 97.4%. Females were more aware of their rights than males for 11 out of
      the 21 patient rights items. Younger adults were more aware than any other age
      group participants. Participants who were admitted to wards of higher categories
      (deluxe rooms) had high degree of awareness about patients' rights and education.
      Patients from urban areas and higher educational status were more aware than
      patients coming from rural areas. Conclusion: The study concludes that effective
      measures should be taken to improve the overall awareness not only among patients
      but also among different stakeholders in the healthcare delivery system.
      Readability of the patients' rights charter with good readability score,
      developing and distributing patient education materials in simple language about
      the rights and responsibilities to the patient and their family/relatives during
      their stay in the hospital or at the time of registration.Continuing nursing and
      medical education in medical teaching institutions and hospitals should focus on
      patients' rights and its importance, its need for awareness and its consequences
      should be taught to students and hospital staff. Patient Right Committee in the
      hospital should be established for supervision monitoring and observance of
      patients' rights.

PMID- 29207737
TI  - Factors Affecting Post Caesarean Pain Intensity among Women in the Northern
      Peninsular of Malaysia.
AB  - Introduction: Caesarean section (CS) rate has increased considerably during the
      past years, accounting for 15% to 25% of births. During post-CS period, moderate
      to severe postoperative pain is a regularly reported problem. Ideally, the
      intensity of postoperative pain should be predicted so as to customize analgesia.
      Aim: To document the CS rate, assess the pain intensity and preoperative factors
      that may predict post caesarean pain among women in the Obstetric unit of a
      Hospital Pulau Pinang in Malaysia. Materials and Methods: A retrospective chart
      review of 400 caesarean deliveries was conducted between January 2013 and June
      2014. The study encompassed patient's demographic data and obstetrics data. The
      overall pain scores since the time of surgery (2, 4, 8, 12, 24 and 48 hours
      postoperatively at rest and while moving) were assessed by visual analogue scale
      (VAS). The data were analyzed by using SPSS software (version 21.0 for Windows).
      Results: The results demonstrate that within a 48 hours postoperative period, the
      average pain at rest and while moving was 0.40+/-0.013 and 0.83+/-0.017 (VAS
      score), respectively. Logistic regression identified that a higher BMI (>=30) (OR
      1.056; 95% CI=1.003 to 1.113, p=0.04), an increase in operation time (> 60
      minutes) (OR 1.009; 95% CI=1.000 to 1.018, p=0.049), Single women (OR 11.597; 95%
      CI=1.382 to 97.320, p=0.024), blood group type O (OR 1.857; 95% CI=0.543 to
      2.040, p = 0.001) and general anesthesia (OR 3.689; 95% CI=1.653 to 8.232,
      p=0.001) were found to be independent predictors for postcaesarean pain
      intensity. Conclusion: This study concluded that CS rate is 28% among women in
      the obstetric unit of a Hospital Pulau Pinang and the pain experienced by the
      study participants was mild. Moreover, the predictive factors for pain intensity
      may aid in identifying patients at greater risk for postoperative pain. This
      study concluded that the predictive methods proposed may aid in identifying
      patients at greater risk for postoperative pain.

PMID- 29207738
TI  - Medical Education Terminologies: Do These Really Percolate to the Level of
      Medical Students? A Survey.
AB  - Introduction: In Medical Education Technology, many terminologies are embodied in
      faculty training programs; used by teachers in daily practice like learning
      objectives, curriculum, and domains, formative and summative assessments. The
      awareness and knowledge of students regarding these terminologies, is
      questionable. Aim: To assess the awareness and knowledge of the students of all
      phases of MBBS - regarding terminologies in medical education. Materials and
      Methods: The study was questionnaire based survey at a private medical college in
      rural setting. Participants were the students from first, second, third Part I
      and third part II MBBS. Sample size included 175, 161,150 and 162 participants of
      first, second, third Part I and third Part II MBBS respectively. The
      questionnaire included 10 closed and one open ended questions which included the
      themes in educational spiral like: learning objectives, teaching-learning and
      assessment.Statistical data analysis was done by using descriptive and
      inferential statistics (Chi-square test) and p<0.05 was considered as level of
      significance. Qualitative data was analysed using coding and categorization.
      Results: Percentage of students participated for first, second, third Part I and
      third Part II MBBS were 87.5%, 80.09%, 93.16% and 90% respectively. The students
      were aware of some terms like learning objectives, its importance, curriculum;
      but knowledge component was missing. For some terms like cognitive, psychomotor,
      affective domain, simulation, formative, summative assessment; awareness as well
      as knowledge was missing. The methods suggested by students regarding the
      terminologies ranged from explanation of importance of these terms to its
      application. Conclusion: Efforts should be made in the direction to increase the
      awareness and knowledge of the basic terminologies used in medical education
      technology.

PMID- 29207739
TI  - Assessment of Palliative Care Awareness among Undergraduate Healthcare Students.
AB  - Introduction: Palliative care knowledge is being given meager importance in the
      curriculum of medical and other allied medical sciences. It is vital that all
      health care practitioners including medical, pharmacy, physiotherapy and nursing
      are aware and apply the best principles of palliative care. Aim: To assess the
      awareness of palliative care among undergraduate students of medical, nursing,
      pharmacy and physiotherapy. Materials and Methods: The study population included
      total of 200 students. Among 200 students, 50 were from each of the colleges of
      medicine, nursing, pharmacy and physiotherapy. After obtaining informed consent,
      questionnaire was given. The questionnaire contained the sociodemographic profile
      and 35 statements under nine groups, for which the respondents were expected to
      answer one out of the three options (Yes, No, Don't know). The groups of
      statements deal with palliative care definition, its philosophy, communication
      issues, non-pain symptoms, medications use and context of application of
      palliative care. Results: It was found that less than 20% of nursing students
      were unaware of palliative care. Among the undergraduates of college of pharmacy,
      more than 50% had no knowledge of palliative care. More than 80% of
      physiotherapy, nursing and medical students agree that death should occur without
      any pain or symptoms. The need of palliative care was well understood by more
      than 70% of students of physiotherapy, pharmacy, nursing and medical colleges.
      Conclusion: Basic knowledge about palliative care was inadequate among the
      undergraduate students related to healthcare.

PMID- 29207740
TI  - Risk Factors for Kidney Stones in Rural Puducherry: Case-Control Study.
AB  - Introduction: Renal stone is a distressing chronic condition which is getting
      common across the world. The rigorous evidence on multiple risk factors of kidney
      stone from a single study is limited. Aim: To find out the social and dietary
      risk factors responsible for the occurrence of kidney stone in a local community
      in rural Puducherry, India. Materials and Methods: It was a hospital-based
      unmatched case-control study. Based on existing information, a sample of 70 cases
      and 140 controls was calculated and considered adequate. The exposure information
      on recent cases was uniformly collected by interview and review of radiologic
      records and exposure information for controls was collected through interviews.
      Associations between the occurrence of renal stone as a dependent variable and
      multiple independent variables such as age, sex, socioeconomic status, type of
      family, religion, the source of drinking water and dietary practices were studied
      by using multiple logistic regression analysis. Results: We found associations of
      occurrence of kidney stone with genetic predisposition (OR:16.98, CI;3.02-95.25),
      less frequency of urine per day (OR:5.95, CI;1.03-34.19) and dietary habit of
      eating red meat once a week (OR:32.28, CI; 9.7-143.2) and even once a month
      (OR:5.20, CI;1.44-18.77). Conclusion: The risk of kidney stone was found high
      among those who had genetic predisposition, less frequency of urination per day
      and those who consumed red meat once a month or more. Patients and local
      community should be educated to reduce the red meat consumption and increase the
      consumption of water and fluid, especially during the hot climates.

PMID- 29207741
TI  - Prevalence of Chronic Morbidity and Sociodemographic Profile of Police Personnel 
      A Study from Gujarat.
AB  - Introduction: The police personnel are special group of population that work for
      minimum 12 hours a day. They are at risk of various types of chronic morbidities.
      Aim: To determine the sociodemographic, chronic morbidity and health profile of
      police personnel of Vadodara district. Materials and Methods: It was a cross
      sectional study conducted on the police force of Vadodara district, Gujarat,
      India. The present study was the outcome of health checkup camp for police
      personnel. Total 982 police personnel participated in the aforementioned study.
      Information regarding the sociodemographic profile, addiction to alcohol
      drinking, tobacco chewing or smoking, diagnosed chronic morbidities, BMI, blood
      sugar and history of exercise and yoga was collected. Data collected was entered
      into Microsoft Excel 2007 and analysed by using Epi-Info 7. Statistical methods
      used included frequencies and proportions for categorical data while range, mean
      and standard deviation were calculated for continuous data. For bivariate
      analysis, Chi-square test was used. Results: In the study population, 95.10% were
      males. The prevalence of chronic morbidity, hypertension and diabetes were 9.5%,
      5% and 2.6% respectively. About 47.05% had normal BMI and mean BMI was 24. The
      study revealed that 7.64% police personnel had the habit of smoking, 3.16%
      consumed alcohol whereas 24.03% consumed tobacco products. It was found that 138
      (14.05%) were active in sports and 304 (30.95%) were actively involved in
      exercise while 44 (4.48%) were involved in yoga. Conclusion: The prevalence of
      hypertension (5%) and diabetes (2.6%) were low as compared to the general
      population (NFHS-4). This can be attributed to health consciousness prevalent
      among the population. A substantial number of study population were involved in
      sports, exercise and yoga.

PMID- 29207742
TI  - Use of Multi-Response Format Test in the Assessment of Medical Students' Critical
      Thinking Ability.
AB  - Introduction: To evaluate students critical thinking skills effectively, change
      in assessment practices is must. The assessment of a student's ability to think
      critically is a constant challenge, and yet there is considerable debate on the
      best assessment method. There is evidence that the intrinsic nature of open and
      closed-ended response questions is to measure separate cognitive abilities. Aim:
      To assess critical thinking ability of medical students by using multi-response
      format of assessment. Materials and Methods: A cross-sectional study was
      conducted on a group of 159 undergraduate third-year medical students. All the
      participants completed the California Critical Thinking Skills Test (CCTST)
      consisting of 34 multiple-choice questions to measure general critical thinking
      skills and a researcher-developed test that combines open and closed-ended
      questions. A researcher-developed 48-question exam, consisting of 8 short-answers
      and 5 essay questions, 19 Multiple-Choice Questions (MCQ), and 16 True-False (TF)
      questions, was used to measure critical thinking skills. Correlation analyses
      were performed using Pearson's coefficient to explore the association between the
      total scores of tests and subtests. Results: One hundred and fifty-nine students
      participated in this study. The sample comprised 81 females (51%) and 78 males
      (49%) with an age range of 20+/-2.8 years (mean 21.2 years). The response rate
      was 64.1%. A significant positive correlation was found between types of
      questions and critical thinking scores, of which the correlations of MCQ (r=0.82)
      and essay questions (r=0.77) were strongest. The significant positive
      correlations between multi-response format test and CCTST's subscales were seen
      in analysis, evaluation, inference and inductive reasoning. Unlike CCTST
      subscales, multi-response format test have weak correlation with CCTST total
      score (r=0.45, p=0.06). Conclusion: This study highlights the importance of
      considering multi-response format test in the assessment of critical thinking
      abilities of medical students by using both open and closed-ended response
      questions.

PMID- 29207743
TI  - Comparison of Microbiological Flora in the External Auditory Canal of Normal Ear
      and an Ear with Acute Otitis Externa.
AB  - Introduction: Acute Otitis Externa (AOE) is also known as swimmer's ear.
      Investigations initiated during World War II firmly established the role of
      bacteria in the aetiology of Acute Otitis Externa. Aim: To culture the
      microbiological flora of the normal ear and compare it with the flora causing AOE
      and to know the role of normal ear canal flora and anaerobes in the aetiology.
      Materials and Methods: A prospective observational study was conducted on 64
      patients clinically diagnosed with unilateral AOE. Ear swabs were taken from both
      the ears. Microbiological flora was studied considering diseased ear as test ear
      and the normal ear as the control. Aerobic and anaerobic cultures were done.
      Severity of the disease was assessed by subjective and objective scores. Effect
      of topical treatment with ichthammol glycerine pack was assessed after 48 hours
      and scores were calculated again. Patients with scores < 4 after pack removal
      were started on systemic antibiotics and were assessed after seven days of
      antibiotics course. Data was analysed using Paired t-test, Wilcoxon signed ranks
      test and Chi-square test. A p-value < 0.05 was considered significant. Results:
      Pseudomonas aeruginosa (33%) was the most common bacteria cultured from the ear
      followed by Methicillin Resistant Staphylococcus aureus (MRSA) (18%). Patients
      with anaerobic organism in the test ear had severe symptoms and needed systemic
      antibiotic therapy. Conclusion: Most of the cases may respond to empirical
      antibiotic therapy. In cases with severe symptoms and the ones refractory to
      empirical treatment, a culture from the ear canal will not be a tax on the
      patient. This helps in giving a better understanding about the disease, causative
      organisms and helps in avoiding the use of inappropriate antibiotics that usually
      result in developing resistant strains of bacteria.

PMID- 29207744
TI  - Awareness of Presbyopia among Rural Female Population in North Karnataka.
AB  - Introduction: Presbyopia is an age related loss of lens accommodation resulting
      in inability to read and/write or to do near work. Though literacy level may be
      low in rural female population of South India, but household works like sewing,
      sorting grains and operating mobile phones must be difficult due to presbyopia.
      Aim: To determine the awareness of presbyopia in rural females; also, to
      determine the knowledge levels regarding presbyopia, spectacle coverage and
      reasons for not wearing spectacles. Materials and Methods: A hospital based cross
      sectional study was conducted at SDM College of Medical Sciences, Dharwad,
      Karnataka, India, on 1000 female subjects of age group 35 years and above coming
      from rural area (around Dharwad). They were examined and open-ended questionnaire
      was used to record subject's awareness and knowledge about presbyopia and their
      responses were analysed. Results: More than 2/3rd of 1000 (66.7%) subjects were
      not aware about presbyopia. More than 50% subjects had difficulty in cleaning
      grains, threading needles and reading fine newspaper print. About 86.5% thought
      presbyopia is age related and 92.2% thought it could be treated with spectacles.
      In spite of high prevalence, almost 98% of the population were not willing to
      wear glasses among which majority (60.2%) felt that spectacles were difficult to
      be maintained while working. In the present study, no statistical significance
      between literacy and awareness was noted (p=0.46). Conclusion: High prevalence of
      presbyopia was seen with majority of them uncorrected due to lack of awareness or
      unwillingness to wear glasses. We need to provide better health education
      regarding presbyopia among both literate and illiterate individuals. Thus, there
      is a need to create awareness and to provide affordable, accessible and
      compatible optical services to the affected population.

PMID- 29207745
TI  - Bilateral Persistent Hyperplastic Primary Vitreous - A Rare Case Report.
AB  - Persistent Hyperplastic Primary Vitreous (PHPV), now-a-days referred to as
      Persistent Fetal Vasculature (PFV), is a rare congenital anomaly of the eye that
      typically presents unilaterally with white pupillary reflex and microphthalmia
      without systemic associations. Bilateral presentations are rare. Here we report a
      case of 15-year-old male with bilateral PFV without leucokoria who was
      misdiagnosed as congenital esotropia with amblyopia, treated for refractive
      errors and referred to higher centre for squint corrections. The diagnosis of PFV
      was made easily on slit lamp examination with dilated pupil due to media clarity.
      Findings were confirmed by colour doppler ultrasonography of the eyes. This case
      warrants essential screening of the posterior segment of all children with
      deviated eyes to ensure earliest detection of such pathologies.

PMID- 29207746
TI  - Dengue Stings the Eye!
AB  - Dengue is a vector borne viral fever and has varied ocular affections. We report
      two cases of Dengue Associated Maculopathy (DAM). The first patient was a 22-year
      old lady with dengue fever, presented with diminution of vision in the left eye
      with best corrected visual acuity of 20/40. Fundus revealed soft exudates and
      streak haemorrhages at the macula in the left eye. Optical Coherence Tomography
      (OCT) showed cystoid macular oedema. She recovered completely within four days.
      The second patient was a 33-year-old lady with dengue, with blurred vision in the
      left eye and with a visual acuity of 20/80. Fundus examination in the left eye
      revealed elevated fovea with a yellow well circumscribed lesion with surrounding
      striations. OCT showed features suggestive of foveolitis. She improved
      spontaneously over the next 21 days to a visual acuity of 20/20p. DAM is usually
      a self-limiting condition with favourable prognosis. This report highlights the
      importance of anticipating visual morbidity in patients with dengue and a
      thorough evaluation and follow-up in spite of its benign behaviour. Also, this
      report highlights the importance of OCT in differentiating various presentations
      of DAM.

PMID- 29207747
TI  - Bilateral Conjunctival Rhinosporidiosis in a Paediatric Patient.

PMID- 29207748
TI  - A Three Year Analysis of Systemic Comorbidities in Cataract Operated Patients in
      India.

PMID- 29207749
TI  - Cirrhosis of Liver and Diabetes Mellitus: The Diabolic Duo?
AB  - Introduction: Cirrhosis of the liver and diabetes mellitus are two chronic
      illnesses with significant impact on the quality of life. Studies from different
      part of the world have shown the combination to be associated with higher
      incidence of complications of cirrhosis and reduced survival. However, data on
      the impact of pre-cirrhotic and post-cirrhotic diabetes on cirrhosis is minimal.
      Aim: The aim of the study was to determine the complications of cirrhosis
      patients with and without co-existent DM and to compare the relation between
      cirrhosis patients with antecedent DM and hepatogenous DM. Materials and Methods:
      The present prospective study was conducted at a tertiary care hospital in
      Kerala, India, over a period of three years. Cirrhosis patients with and without
      diabetes, along with subcategorization as antecedent and hepatogenous diabetes,
      were studied for various complications and outcome including death. Chi-square
      and Mann-whitney tests were used for comparing data. Results: Patients with
      cirrhosis and diabetes had higher incidence of gall stones (27.6% versus 13.2%;
      p=0.008) and urinary infection (29.3% versus 7.5%; p=<0.001). Incidence of
      hepatocellular carcinoma and mortality were similar between the groups. Patients
      with antecedent diabetes and hepatogenous diabetes were similar with respect to
      complications and mortality. Child-Turcotte-Pugh (CTP) score, Model for End stage
      Liver Disease (MELD) score, urinary tract and respiratory infections and duration
      of cirrhosis were independent predictors of mortality in patients with cirrhosis.
      Conclusion: Coexistent diabetes mellitus increases the incidence of complications
      and hospitalizations in cirrhosis patients but without impact on mortality rates.
      There is no significant morbidity or mortality difference between cirrhotics with
      antecedent diabetes and hepatogenous diabetes.

PMID- 29207750
TI  - Validity of Simplified Ankylosing Spondylitis Disease Activity Scores (SASDAS) in
      Indian Ankylosing Spondylitis Patients.
AB  - Introduction: Ankylosing Spondylitis Disease Activity Score (ASDAS) is a complex
      score for monitoring disease activity in Ankylosing Spondylitis (AS). Aim: To
      develop a simplified version of the ASDAS. Materials and Methods: Consenting 254
      AS patients (modified New York and/or Assessment in Ankylosing Spondylitis 2009
      criteria) were recruited. Sociodemographic data and disease characteristics such
      as Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and
      AS Quality of Life (ASQoL), Erythrocyte Sedimentation Rate (ESR), and C-Reactive
      Protein (CRP) were collected. Simplified ASDAS (SASDAS) was calculated as the
      simple sum of patient global assessment, back pain (BASDAI question no.2),
      peripheral pain and swelling (BASDAI question no.3), morning stiffness (BASDAI
      question no.6), and either ESR in mm/hour (for SASDAS-ESR) or CRP in mg/L (for
      SASDAS-CRP); this sum was divided by 10 to obtain the final score. Results: Most
      patients (224/254; 88.19%) were males with the median age of 30 years. SASDAS-ESR
      and SASDAS-CRP showed good correlation with ASDAS-ESR and ASDAS-CRP respectively
      (r2=0.78 and 0.58 respectively; p-value<0.0001). SASDAS-ESR showed good
      correlation with CRP (r=0.50) and is fairly correlated with backpain (r=0.19),
      morning stiffness (r=0.21) and peripheral pain (r=0.21); SASDAS-CRP showed good
      correlation with BASFI (r=0.32), and ESR (r=0.55) (all p-value<0.0001). Using
      established ASDAS cut-off values, corresponding cut-off points between
      'inactive', 'moderate', 'high', and 'very high' disease activities (with optimum
      sensitivity and specificity) were 1.83, 2.45 and 4.45 for SASDAS-ESR, and 0.79,
      1.50, and 3.26 for SASDAS-CRP. Both the SASDAS scores showed good correlation
      with BASDAI. Conclusion: SASDAS-ESR and SASDAS-CRP are reliable, easy-to
      calculate scores for disease activity assessment in Asian Indian AS patients;
      which can be used in daily clinical practice.

PMID- 29207751
TI  - Does Azithromycin and Cetirizine Combination Given for Upper Respiratory Tract
      Infections has any Significant Effect on QTc?
AB  - Introduction: Azithromycin usage in patients with baseline cardiovascular risk is
      associated with increased risk of cardiovascular mortality, following which Food
      and Drug Administration (FDA) issued a black box warning regarding safety of
      azithromycin in patients with cardiovascular morbidity particularly with
      prolonged QTc. Cetirizine is a second generation anti histaminic and is found to
      be commonly used for Upper Respiratory Tract Infections (URIs) along with
      azithromycin on outpatient basis. Whether, usage of these two drugs in
      combination confers a similar risk, is unknown. Aim: To assess the effect on QTc
      among patients treated with azithromycin and cetirizine combination for upper
      respiratory tract infection. Materials and Methods: We conducted a prospective
      longitudinal study from August 2014 to July 2016. The study was done on 45
      patients above 18 years of age without any cardiovascular morbidity in whom
      azithromycin and cetirizine were prescribed for upper respiratory tract
      infections. We compared the QTc on day 1 and day 4. Data was analysed using
      Student's paired t-test. Results: During three days of azithromycin and
      cetirizine for upper respiratory tract infections, we observed that on day 4
      there was significant increase in QTc in 43 patients (95.6%) as compared with the
      QTc on day 1. We also observed that in 8 (17.8%) out of 45 patients, QTc on day 4
      crossed the upper limit of normal {430 milliseconds (ms)}, but this was not
      statistically significant. However, analysing these eight patients, we obtained
      the baseline QTc of 377.50 ms above which if prescribed, this combination of
      drugs have a chance of prolonging the QTc above 430 ms with a sensitivity of
      87.5% and specificity of 40.5%. Conclusion: During three days treatment with
      azithromycin and cetirizine, there was significant change in QTc between day 1
      and day 4. Patients with baseline QTc greater than 377.5 ms were at risk of QTc
      prolongation above 430 ms on day 4.

PMID- 29207752
TI  - Study of Left Ventricular Mass and Its Determinants on Echocardiography.
AB  - Introduction: Increased Left Ventricular Mass (LVM) is an independent risk factor
      for cardiovascular morbidity and mortality. Aim: This study was done to find the
      prevalence and determinants of LVM in the Northern Indian population. Materials
      and Methods: A prospective cross-sectional observational study was carried out in
      a tertiary care centre in Himachal Pradesh, India and the study population
      included all consecutive patients fulfilling the inclusion criteria attending
      cardiology OPD on seeking medical attention with various symptoms for
      dyslipidaemia, hypertension but not on medication over a period of one year.
      Focused history was taken; physical examination and investigations were done.
      Data collected was analysed using Epi-info software version 3.5.1. We calculated
      means of LVM index for categorical variables i.e., sex, tobacco consumption,
      alcohol consumption and sedentary lifestyle etc., and also calculated p-values as
      test of significance for mean difference across the exposure variable groups. The
      Pearson correlation coefficient was calculated and 2 tailed significance at p<
      0.05 was taken as statistically significant. Results: Mean age of study
      population was 42.30+/-9.8 years and 62.9% were males. The mean LVM index was
      significantly higher in men than in women 77.7 +/- 11.4 vs.71.3 +/- 15.7 (p-value
      <0.01). Strong positive correlation was observed between increased waist hip
      ratio and increased Left Ventricular Mass Index (LVMI). The Pearson correlation
      coefficient was 36.77 and it was statistically significant with p-value 0.04.
      Conclusion: We found positive and independent correlation of increased LVMI with
      increased Waist Hip Ratio (WHR). A positive independent correlation was also
      observed with higher fasting blood sugar levels.

PMID- 29207753
TI  - A Study of Correlation of Neck Circumference with Framingham Risk Score as a
      Predictor of Coronary Artery Disease.
AB  - Introduction: It has been observed that metabolic syndrome is risk factor for
      Coronary Artery Disease (CAD) and exerts its effects through fat deposition and
      vascular aging. CAD has been acknowledged as a leading cause of death. In earlier
      studies, the metabolic risk has been estimated by Framingham risk score. Recent
      studies have shown that Neck Circumference (NC) has a good correlation with other
      traditional anthropometric measurements and can be used as marker of obesity. It
      also correlates with Framingham risk score, which is slightly more sophisticated
      measure of CAD risk. Aim: To assess the risk of CAD in a subject based on NC and
      to correlate the NC to Framingham risk score. Materials and Methods: The present
      cross-sectional study, done at Karnataka Institute of Medical Sciences, Hubli,
      Karnataka, India, includes 100 subjects. The study duration was of one year from
      1st January 2015 to 31st December 2015. Anthropometric indices Body Mass Index
      (BMI) and NC were correlated with 10 year CAD risk as calculated by Framingham
      risk score. The correlation between BMI, NC, vascular age and Framingham risk
      score was calculated using Karl Pearson's correlation method. Results: NC has a
      strong correlation with 10 year CAD risk (p<=0.001). NC was significantly greater
      in males as compared to females (p<=0.001). Males had greater risk of
      cardiovascular disease as reflected by higher 10 year Framingham risk score
      (p<=0.0035). Conclusion: NC gives simple and easy prediction of CAD risk and is
      more reliable than traditional risk markers like BMI. NC correlates positively
      with 10 year Framingham risk score.

PMID- 29207754
TI  - Clinicopathological Characteristics and Outcomes of Diffuse Crescentic
      Glomerulonephritis - A Single Center Experience from Southern India.
AB  - Introduction: Diffuse Crescentic glomerulonephritis (CrGN) is characterized by
      rapidly progressive renal failure and has grave prognosis. There is significant
      regional and temporal variation in aetiology, prevalence and prognosis of diffuse
      crescentic glomerulonephritis (CrGN) with limited data available in adult Indian
      population. Aim: This study aims to identify the aetiology, clinico-pathological
      features and outcomes of diffuse CrGN in south Indian population. Materials and
      Methods: In this retrospective study, clinical records of all adults (>18 years)
      over a 5-year period (2010-2014) with a histopathological diagnosis of diffuse
      CrGN (>50% crescents) were reviewed. Clinical, serological, biochemical and
      histopathological data were collected. Follow-up data at six months including
      renal outcome and mortality were studied. Data was analysed using SPSS version
      15. Results: There were 29 cases of diffuse CrGN accounting for an incidence of
      2.9% among 1016 non-transplant kidney biopsies. The most common cause was pauci
      immune crescentic GN. The median creatinine at admission was 7.2 mg/dl
      {(interquartile range (IR) 3.3 - 10.4)} and 75.9% of patients required
      haemodialysis at admission. Complete/partial recovery was seen in 34.5%. At the
      end of six months 31% were dialysis dependent and the mortality was 27.6%. On
      univariate analysis, the significant predictors of renal loss and mortality were
      oliguria (p=0.02), requirement of haemodialysis and serum creatinine (p=0.001) at
      admission (>5.5mg/dl) (p=0.003). Histopathological features did not influence the
      outcome in our study. Conclusion: In our cohort, the most common cause for
      diffuse CrGN is pauci-immune CrGN. Diffuse CrGN carries a poor prognosis.
      Patients with pauci-immune and AntiGBM disease have worst prognosis compared to
      immune complex CrGN. The presence of oliguria, high serum creatinine and
      requirement of haemodialysis at admission are associated with poor outcomes.

PMID- 29207755
TI  - Correlation of Trace Elements in Patients of Chronic Liver Disease with Respect
      to Child- Turcotte- Pugh Scoring System.
AB  - Introduction: Zinc, copper, manganese and magnesium are essential trace elements
      whose role in chronic liver disease and its complications is not clear. Aim: To
      study the concentration of these elements in patients with Chronic Liver Disease
      (CLD) with respect to Child-Torcotte-Pugh (CTP) scoring. Materials and Methods:
      This was an observational study carried out in the Department of Medicine, JSS
      Hospital, Mysore, India, between October 2013 and October 2015. A total of 75
      patients with cirrhosis were prospectively enrolled. Severity of liver disease
      was assessed based on CTP score and patients were grouped into Class A, B and C.
      Routine investigations were done and following trace elements were assessed in
      all-zinc, copper, manganese and magnesium. Results: The serum concentrations of
      zinc decreased with severity of liver disease, and the mean difference between
      different severity classes was statistically significant (p<0.001). There was a
      significant negative correlation between zinc and CTP Score (r= -0.439; p<0.001).
      Copper concentration was increased in patients with more severe cirrhosis and
      mean level difference of copper among the CTP groups were statistically
      significant (p<0.001). Moreover, copper showed significant positive correlation
      with CTP Score (r=0.385; p<0.001). The serum levels of manganese were
      significantly higher in patients with CTP C class in comparison to patients with
      CTP A and B class (p<0.05); Manganese showed significant positive correlation
      with CTP Score (r=0.271; p= 0.019). The concentrations of magnesium did not
      differ significantly between CTP class with the mean level difference not
      statistically significant. Conclusion: Increasing liver dysfunction alters the
      metabolism of trace elements towards excess of copper and deficiency of zinc.

PMID- 29207756
TI  - Intravenous Fluid Administration and the Survival of Pre hospital Resuscitated
      out of Hospital Cardiac Arrest Patients in Thailand.
AB  - Introduction: Out of Hospital Cardiac Arrest (OHCA) is a leading cause of death
      worldwide. The Emergency Medical Service (EMS) provides early care to critical
      OHCA patients. Pre hospital intervention has been improving OHCA survival rate,
      however it is still unclear for the recommendation of routine infusion of
      Intravenous (IV) fluids during cardiac arrest resuscitation. Aim: This study
      aimed to determine whether IV fluid administration was associated with increasing
      survival of resuscitated OHCA patients and to assess the survival rate of
      resuscitated OHCA patients. Materials and Methods: This cross-sectional
      analytical study was conducted among 33,006 resuscitated OHCA patients who
      received emergency medical service in Thailand. Data set from the EMS Registry of
      the OHCA patients who received Advanced Life Support (ALS) and Cardiopulmonary
      Resuscitation (CPR) during January 2011 to December 2015 was enrolled as per
      inclusion criteria. Data were analysed by using both descriptive statistic and
      multiple logistic regression. Results: The result indicated that 27,270 OHCA
      patients (82.62%:95%CI=82.121-83.030%) survived until they reached hospital. In
      addition, after adjusting for effect modifiers and covariates, it was found that
      adult (>=18 years) with IV fluid administration were more likely to survive
      (adjusted OR=4.389; 95% CI: 3.911-4.744) when compared to children (<18 years)
      with IV fluid administration (adjusted OR =2.952; 95% CI: 2.040-4.273). Other
      factors associated with OHCA patients' survival were female gender (adjusted OR
      =1.151; 95% CI: 1.067-1.241), response time per minutes (adjusted OR =0.993; 95%
      CI: 0.989-0.997), scene time per minutes (adjusted OR=0.948; 95% CI: 0.944-0.952)
      and transport time per minutes (adjusted OR=0.973, 95%CI: 0.968-0.978).
      Conclusion: This study revealed that IV fluid administration was significantly
      associated with survival of OHCA patients while controlled other covariates
      including female gender, response time, scene time and transport time. Therefore,
      it is recommended that the IV fluid administration should be medicated for
      resuscitated OHCA patients.

PMID- 29207758
TI  - Mycobacterium fortuitum Infection at Umbilical Hernioplasty Site.
AB  - Non Tuberculous Mycobacteria (NTM) are a group of rapidly growing mycobacteria
      and are generally considered to be of low virulence. Of late, there has been an
      increase in incidence of infections due to these organisms. Among them,
      Mycobacterium fortuitum, M. chelonae and M. abscessus are the common species
      which have been identified. Though they are occasionally implicated in pulmonary
      infections, NTM are very commonly associated with cutaneous infections,
      especially surgical site infections. Identification of NTM infection at such
      sites should be suspected when there is delayed healing of the wound.
      Histopathological Examination (HPE) of the wound site may reveal a classical
      picture of granulomas, epithelioid cells and giant cells which may lead to a
      suspicion of tuberculosis. It is important to perform mycobacterial culture and
      sensitivity testing of the wound tissue as this helps to differentiate
      tuberculous and non tuberculous infections. Here, we present a case of a patient
      who underwent mesh hernioplasty for umbilical hernia and was diagnosed with M.
      fortuitum infection at the site of umbilical hernioplasty.

PMID- 29207759
TI  - Combined Thrombophilia in a Young Male Presenting as Life Threatening Pulmonary
      Embolism.
AB  - Combined hereditary thrombophilia is an uncommon entity associated with higher
      risk of early onset thrombosis. We report a case of 39-year-old male with
      combined deficiency of natural anticoagulants (protein C, S and anti thrombin)
      along with hyper homocystenemia and factor V Leiden mutation, presenting with
      life threatening bilateral pulmonary embolism. The clinical implications of
      combined thrombophilia are also discussed.

PMID- 29207757
TI  - Vitamin D Levels and Associations in Indian Patients with Primary Sjogren's
      Syndrome.
AB  - Introduction: Vitamin D is a steroid hormone belonging to the class of
      secosteroids with myriad immune functions and has been implicated in
      aetiopathogenesis of various autoimmune diseases. Although, there have been
      various studies showing the association of vitamin D in rheumatoid arthritis and
      lupus in different populations, there have been limited studies on vitamin D and
      primary Sjogren's Syndrome (pSS). There are no studies on association of vitamin
      D and pSS from any tropical country including Indian subcontinent. Aim: The
      purpose of the study was to look for any association between 25-hydroxyvitamin D
      (25(OH)D) levels and disease manifestations in Indian patients with pSS.
      Materials and Methods: This is a retrospective cross-sectional study done at a
      tertiary teaching hospital in southern India in 235 patients with pSS. Patients
      satisfying the American European Consensus Group (AECG) or American College of
      Rheumatology (ACR) 2012 for pSS between 2008 and 2015 were included if baseline
      25(OH)D levels using electrochemiluminescence were available in hospital's
      laboratory record, 25(OH)D <20 ng/ml,20-30 ng/ml and >30 ng/ml was defined as
      deficiency, insufficiency and normal, respectively. Clinical laboratory data and
      disease activity scoring by EULAR Sjogren's syndrome disease activity index
      (ESSDAI) were retrieved retrospectively. Latitude corresponding to residence of
      each patient and the season of performing the assay were recorded. Chi-square
      statistics was done to find associations between categorized 25(OH)D and outcomes
      and was reported as odds ratio(95% confidence interval). Results: Mean 25(OH)D
      for 235 patients with pSS was 19.98(12.55)ng/ml. A vitamin D deficiency,
      insufficiency and sufficiency was seen in 141(60%), 60(25.5%) and 34.0(14.5%),
      respectively. No association was noted between latitude or season of performing
      assay and the levels. pSS with 25(OH)D <=30ng/ml had more than two fold risk of
      higher grading on lip biopsy as well as Rheumatoid Factor (RF) positivity.
      However, low 25(OH)D seemed to be associated with lower ESSDAI and less pulmonary
      involvement. Conclusion: Prevalence of 25(OH)D deficiency in Indian patients with
      pSS was comparable to that of general Indian population. Low 25(OH)D level
      <=30ng/ml was associated with higher odds for RF positivity and positive grading
      on lip biopsy. Surprisingly, low 25(OH)D was associated with lower ESSDAI score.

PMID- 29207760
TI  - Epituberculosis Revisited: Case Report and Review.
AB  - Primary pulmonary tuberculosis can involve regional lymph nodes which may resolve
      spontaneously or on treatment; or they may enlarge causing extrinsic bronchial
      compression; or cause endobronchial inflammation and ulceration; or a node may
      erode through the bronchial wall with extrusion of caseous materials into the
      bronchial tree, causing focal or lobar pneumonia. This erosion is seen
      radiologically as hilar lymphadenopathy, with atelectasis and consolidation and
      described as "epituberculosis". It is more common in infants than older children.
      We hereby describe the case of a 13-year-old child with right hilar
      lymphadenopathy and right upper lobe consolidation on chest x-ray. We
      demonstrated by fibreoptic bronchoscopy that this epituberculosis resulted from
      perforation of a lymph node and discharge of caseous material into the upper lobe
      bronchus with resultant endobronchial obstruction. Thus a tuberculous ruptured
      lymph node may lead to clinical and radiological worsening, but this does not
      indicate development of drug resistance in these patients and they respond well
      to the same treatment regimen.

PMID- 29207761
TI  - Foreign Body Aspiration: An Unusual Presentation and Outcome.
AB  - Foreign body aspiration mostly presents as acute emergency with cough, choking
      and dyspnoea. Rarely aspiration of foreign body may be the underlying cause in
      patients presenting with long term symptomatologies. Here is a case of 60-year
      old male who came for surgical management of cholelithiasis. During his workup, X
      ray chest revealed right paracardiac opacity. Fibre-optic bronchoscopy showed a
      mass lesion in right main bronchus. It was taken out of the airways by flexible
      bronchoscope but could not be retrieved. Subsequent chest radiographs showed
      marked improvement.

PMID- 29207762
TI  - Guillain-Barre Syndrome with Falciparum Malaria and Scrub Typhus Mixed Infection
      An Unusual Combination.
AB  - Guillain-Barre Syndrome is very rare in parasitic and rickettsial infection. Here
      we report a case of Plasmodium falciparum and scrub typhus mixed infection,
      presented with quadriparesis. Clinical, Serological, CSF analysis and Nerve
      Conduction Studies were consistent with Acute Inflammatory Demyelinating
      Polyneuropathy (variant of GBS). After administration of antimalarials and
      antibiotics for the mixed infection, patient gradually improved.

PMID- 29207763
TI  - Carbamazepine Induced Thrombocytopenia.
AB  - Antiepileptic Drugs (AEDs) are commonly associated with haematological disorders,
      including anaemia, thrombocytopenia, neutropenia and even bone marrow failure.
      Fatal disorders like aplastic anaemia are uncommon. On exploring through the
      literature, older AEDs are more associated with haematological alterations than
      newer AEDs, and careful monitoring is warranted especially with phenytoin,
      carbamazepine and valproate. The exact cause of these alterations is not
      established, though immune mechanisms and pharmacology of individual drugs are
      the proposed mechanisms, a further research along this path is underway. Of worth
      mentioning here, this predilection of older AEDs towards haematological disorders
      is pronounced in children compared to adults. We present here a case of
      congenital heart disease with history of brain abscess and seizures, on
      carbamazepine who presented to our hospital with toothache. Routine screening
      prior to tooth extraction revealed thrombocytopenia. Further evaluation revealed
      the association of carbamazepine and thrombocytopenia, which mandated
      discontinuation of drug and switching patient to alternative AED.

PMID- 29207764
TI  - Spontaneous Renal Artery Thrombosis Successfully Intervened with Drug Eluting
      Stent: A Primary Renal Artery Angioplasty.
AB  - Renal artery thrombosis is a rare medical emergency and needs to be diagnosed
      early and treated urgently to prevent irreversible renal injury. We report a case
      of 35-year-old male, who presented with the total thrombotic occlusion of right
      renal artery and was managed with percutaneous transluminal angioplasty with a
      drug eluting stent.

PMID- 29207765
TI  - Syndrome of Inappropriate Secretion of Antidiuretic Hormone Preceding Guillain
      Barre Syndrome.
AB  - Guillain-Barre Syndrome (GBS) is an inflammatory polyradiculoneuropathy which is
      known to produce syndrome of inappropriate Secretion of Antidiuretic Hormone
      (SIADH). However, the hyponatremia is usually seen after the onset of weakness.
      Here, we report a case of SIADH that presented with hyponatremic seizures which
      preceded the onset of GBS by ten days.

PMID- 29207766
TI  - Successful Management of Urosepsis with Ceftriaxone+Sulbactam+EDTA: A Case Report
      of Penem Sparing Approach.
AB  - Over the past decade, the Anti-Microbial Resistance (AMR) among members of
      Enterobacteriaceae family is on rise mainly due to rapid spread of strains
      producing Extended-Spectrum Beta-Lactamases (ESBLs) and Metallo Beta-Lactamases
      (MBLs). Hence, the choice of drugs available for these resistant strains is
      diminishing and their treatment is becoming more challenging. This is a case of
      complicated Urinary Tract Infection (cUTI) due to ESBL producing E. coli leading
      to septic shock which was successfully managed with Antibiotic Adjuvant Entity
      (AAE), a combination of ceftriaxone+sulbactam+EDTA.

PMID- 29207767
TI  - Clinical Utility of Blood Cell Histogram Interpretation.
AB  - An automated haematology analyser provides blood cell histograms by plotting the
      sizes of different blood cells on X-axis and their relative number on Y-axis.
      Histogram interpretation needs careful analysis of Red Blood Cell (RBC), White
      Blood Cell (WBC) and platelet distribution curves. Histogram analysis is often a
      neglected part of the automated haemogram which if interpreted well, has
      significant potential to provide diagnostically relevant information even before
      higher level investigations are ordered.

PMID- 29207768
TI  - Controversies in Serotonin Syndrome Diagnosis and Management: A Review.
AB  - Over the past few years, Serotonin Syndrome (SS) has become a significant
      clinical concern. Over the last decade, United States saw a surge in
      antidepressant use. SS characteristically presents as the triad of altered mental
      status, autonomic dysfunction and neuromuscular excitation. Symptoms vary from
      patient to patient with mild cases presenting with subacute symptoms and severe
      cases progressing rapidly to death. Due to the protean manifestations of the
      syndrome along with non-specific prodromal, SS can easily be misdiagnosed if not
      carefully assessed. In severe cases, SS can be mistaken as neuroleptic malignant
      syndrome while mild cases are mostly misattributed to other causes such as flu.
      SS is a clinical diagnosis and therefore, requires a thorough review of
      medications and physical examination. Given the protean nature of this
      toxicologic syndrome various criteria were defined which includes Sternbach's,
      Radomski and Hunter's criteria. Keeping in mind the wide symptoms of serotonin
      syndrome from being barely perceptible to lethal emphasis there is a need to
      treat the syndrome on urgent basis. Mainstay for treatment of serotonin syndrome
      is to discontinue the offending drug. Improvement is seen in most patients within
      24 hours.

PMID- 29207769
TI  - Brugada Syndrome with Spontaneous Fluctuation in ECG Pattern.

PMID- 29207770
TI  - Making Nutrition Management Scientific, Objective and Simple with the Help of
      Technology.
AB  - Nutrition management is one of the cornerstones of care in the management of
      hospitalized patients, especially, for those who are critically ill. Significant
      numbers of hospitalized patients have alteration in appetite and the function of
      the gastrointestinal tract. Calculating the caloric goal, prescribed proteins to
      be delivered in a finite amount of water at a certain rate is the need of the
      hour and it becomes a daunting task to complete daily. With the help of
      technology such tasks can be completed easily and accurately. This suggestion
      based software called as "iNutriMon" helps to screen out the patients which are
      at risk of malnutrition, formulate a plan, monitor and manage enteral nutrition
      of patients by calculating calories, proteins and water intake as per the patient
      requirement.

PMID- 29207771
TI  - Aspects of Evolving Genito Urinary Tuberculosis-A Profile of Genito Urinary
      Tuberculosis (GUTB) in 110 Patients.
AB  - Introduction: Genito Urinary Tuberculosis (GUTB) is a widespread disease seen in
      urology practice. The true incidence and prevalence of GUTB is difficult to
      estimate because a large number of patients remain asymptomatic. Aim: To
      recognize typical and atypical clinical and radiological features of tuberculosis
      and to emphasize the need for diagnosing GUTB early. Materials and Methods: This
      was a retrospective study conducted in 110 cases of GUTB diagnosed and treated in
      two teaching institutions over a period of three years, from July 2002 to June
      2005. A detailed history, thorough clinical examination, urine examination,
      culture for tubercle bacillus, imaging studies, cystoscopy and histological and
      serological examination were done to arrive at a diagnosis. Results: Fifty six
      patients (51%) were in the age group of 21-40 years. The male: female ratio was
      1.4: 1. Loin pain was the most common symptom observed in 27% of the patients.
      Intravenous Urogram (IVU) revealed non-visulalised kidney in 25 patients (23%),
      hydronephrosis or hydrouretero nephrosis in 34 patients (31%) and distortion,
      cavitation or scarring of the calyces in 16 patients (14.5%). Five of them had
      thimble bladder. In 14 patients, IVU appeared normal. About 28 patients (25%)
      were treated conservatively with anti tuberculosis therapy. Twenty one of them
      (19%) underwent Nephrectomy and 10 patients had reconstructive procedures.
      Conclusion: A peculiarity of most of our patients was a late presentation with
      advanced disease. Most patients were asymptomatic or ignorant. Slow but
      continuous infection causes a destruction of renal parenchyma and the healing
      process leads to renal parenchymal loss. If identified early and treated
      appropriately, GUTB is a curable condition.

PMID- 29207772
TI  - Comparison of Pain Relief from Different Intravenous Doses of Ketorolac after
      Reduction of Mandibular Fractures.
AB  - Introduction: Pain is an unpleasant feeling due to tissue destruction, which
      disturbs an individual's daily routines even at its lowest levels. The majority
      of surgeons and anaesthesiologists are increasingly trying to administer non
      opioid analgesics because excessive use of opioids after surgery results in
      patient dissatisfaction. Aim: To evaluate the analgesic effect of intravenous
      injection of different doses of ketorolac at different intervals in patients
      undergoing surgery for unilateral fractures of the mandible. Materials and
      Methods: In the present randomized clinical trial (March 2016 to January 2017, in
      Tabriz Imam Reza Treatment/Educational Center), 50 patients were assigned to five
      groups with simple randomization method. In Group 1 and 2, immediately before the
      induction of general anaesthesia 30 and 60 mg of ketorolac and in Group 3 and 4,
      immediately before termination of surgery 30 and 60 mg of ketorolac was injected
      intravenously. In Group 5, ketorolac was not administered. After each patient
      regained complete consciousness, the severity of pain was determined using VAS up
      to 24 hours at baseline and at 2, 4, 6, 12 and 24-hours intervals. The total dose
      of the opioid analgesic agent (morphine-pethidine) and the time for the first
      request for an analgesic agent were recorded for each patient and their means
      were compared in each group with suitable statistical tests. Results: The
      patients in Group 5 and 4 exhibited the highest and lowest mean pain scores
      (5.03+/-0.9 and 3.5+/-1), respectively. ANOVA for repeated measures and post-hoc
      Tukey tests showed significant differences only between Group 3 and 5 (p=0.002)
      and Group 4 and 5 (p=0.001), with no significant differences between the other
      groups (p>0.005). The highest dose of the analgesic agent was in Group 5 (5.3+/
      1.4 mg) and the lowest dose was recorded in Group 4 (1.6+/-0.6 mg). Patients in
      the control group received significantly higher doses compared to the other
      groups (p<0.05). The patients in Group 1 and 2 received higher doses of
      analgesics compared to Group 3 and 4 (p<0.05). The longest time for the request
      for the first dose of analgesic agent after surgery was 73.4+/-12.03 minutes in
      Group 4 The patients in the control group had requested analgesics after surgery
      at a significantly shorter time compared to the patients in all the study groups
      (p<0.05). The patients in Group 1 and 2 had requested analgesics at a shorter
      time after surgery compared to the subjects in Group 3 and 4 (p<0.05).
      Conclusion: Intravenous administration of 30 and 60 mg of ketorolac, immediately
      before termination of surgery, decreases the pain severity and the need for
      opioid analgesics after surgery.

PMID- 29207773
TI  - Testicular and Epididymal Metastasis from Prostate Carcinoma: A Rare
      Manifestation of Common Disease.
AB  - Carcinoma prostate secondary metastasis to testicle and epididymis is rare. We
      report a case of metastatic carcinoma prostate in which testicular and epididymal
      metastasis were diagnosed incidentally in bilateral orchiectomy specimen.
      Testicular and para testicular structure should be properly evaluated for
      accurate staging of carcinoma prostate. Epididymis should always be included in
      bilateral orchidectomy specimen.

PMID- 29207774
TI  - A Diagnostic Surprise For A Right Iliac Fossa Mass - A Perforated Ileal
      Gastrointestinal Stromal Tumour.
AB  - Gastrointestinal Stromal Tumours (GISTs) are tumours of the gut found mostly in
      stomach and small intestine. The complications are Gastrointestinal (GI)
      bleeding, obstruction, pain and rarely perforation. We are reporting an abnormal
      presentation of GIST masquerading as an acute abdomen with Right Iliac Fossa
      (RIF) mass in 60-year-old lady. Contrast Enhanced Computed Tomography (CECT) of
      abdomen revealed a peripherally enhancing encapsulated abscess in RIF in close
      contact with base of caecum and adjacent peritonitis suggesting caecal
      perforation. On laparotomy, a gangrenous perforated ileal GIST was identified
      along the antimesenteric border of ileum. Pathological examination confirmed the
      tumour to be a GIST of spindle cell type, further reiterated by
      immunohistochemistry. Our case report emphasizes, GIST as a rare and unusual
      differential diagnosis of RIF mass, and to have high degree of clinical suspicion
      when a similar situation is encountered in an emergency scenario, keeping in mind
      the poor outcome due to delay in appropriate management of the disease.

PMID- 29207775
TI  - Axial Torsion of Meckel's Diverticulum: A Rare Case Report.
AB  - Meckel's Diverticulum (MD) is the most common congenital anomaly of
      gastrointestinal tract, occurring in 2% of the population. It is a true
      diverticulum and histologically all four intestinal layers are present within MD.
      There are various complications related to a Meckel's diverticulum, including
      haemorrhage, intestinal obstruction, inflammation and perforation. Axial torsion
      followed by gangrene of MD is the rarest of the complications that have been
      reported. The exact mechanism for torsion is unclear. Preoperative diagnosis of
      torsion of MD is difficult and often confused with appendicitis as pain is
      usually localized to right lower quadrant. Radiological investigations do not
      provide much help in diagnosis. We report a case of axial torsion of MD
      presenting as acute abdomen in an 11-year-old female patient. The diagnostic
      laparoscopy was performed. Confirmatory diagnosis and further surgical management
      was done by exploratory laparotomy under general anaesthesia.

PMID- 29207776
TI  - Primary Adenocarcinoma of the Bulbomembranous Urethra in a 33-Year-Old Male
      Patient.
AB  - Primary Urethral Carcinoma (PUC) is considered as a rare tumour, accounts for
      less than 1% of all malignancies and an incidence rate of four cases per million
      patients. Incidence increases with the patient's age and most commonly present in
      seventh decades. Urothelial carcinoma is the most common type (76%) of the PUC,
      adenocarcinoma accounts for less than 5% of the PUC. No definitive protocol for
      tumour management for urethral adenocarcinoma has been described in the
      literature due to lack of prospective study and scarcity of the cases. Treatment
      usually depends on the site and stage of the tumour. We hereby report a case of
      33-year-old male patient with urethral adenocarcinoma of bulbomembranous urethra
      spread to the prostatic urethra and left side inguinal lymph node. He was treated
      through multimodal therapy with surgery plus adjuvant chemotherapy.

PMID- 29207777
TI  - An Aggressive Primary Retroperitoneal Diffuse Large B-Cell Lymphoma Mimicking a
      Pancreatic Neoplasm, Presenting as Duodenal Stenosis.
AB  - Diffuse Large B-Cell Lymphoma (DLBCL) is the most common histological subtype of
      Non-Hodgkin's Lymphoma (NHL). Primary retroperitoneal DLBCL is uncommon and has
      seldom been reported. Extrinsic compression of the duodenum due to lesions
      originating from the retroperitoneum is also rare. We present a case of a 39-year
      old man who presented with inability to tolerate oral intake, abdominal pain, an
      upper abdominal mass and postprandial bilious vomiting caused by a large DLBCL
      arising from the retroperitoneum causing extrinsic compression of the duodenum.
      The cause of compression was initially presumed to be a neoplasm arising from the
      uncinate process of the pancreas or duodenum because of its proximity to the
      uncinate process and apparent widening of the C loop of duodenum. Repeat Computed
      Tomography (CT) scans were obtained because of the rapid increase in the size of
      the mass, normal levels of tumour markers such as Cancer Antigen (CA) 19-9,
      Carcinoembryonic Antigen (CEA) and no evidence of jaundice in spite of the large
      size of the mass. It revealed encasement of the uncinate process of pancreas with
      no involvement of parenchyma of the pancreas, thereby mimicking a pancreatic
      tumour. The neoplastic lymphoid cells were positive for Leukocyte Common Antigen
      (LCA), Cluster of Differentiation (CD)20, CD10, B-cell Lymphoma 2 (Bcl-2) and
      were negative for Creatine Kinase (CK), CD23, CD30, Anaplastic Lymphoma Kinase
      (ALK) and cyclin D1, D3 and D5. The Ki67 proliferative index was greater than
      95%. Retroperitoneal DLBCL although rare should be considered in cases of
      duodenal obstruction.

PMID- 29207778
TI  - Delayed Tension Pneumothorax - Identification and Treatment in Traumatic
      Bronchial Injury: An Interesting Presentation.
AB  - A 13-year-old girl, who did not receive any treatment for few hours following
      Road Traffic Injury (RTI), reported to the Casualty Department and found to have
      patent airway with clinically normal C spine, air-hunger (RR 42/minute), trachea
      deviated to left, distended neck veins and absent breath sounds on the right
      side. The chest X-ray she carried, done immediately after the injury, showed
      right sided tension pneumothorax. She was put on oxygen at 11 L/minute and an
      Intercostal chest tube drainage (ICD) was inserted on right side. Her oxygen
      saturation (40%) failed to improve. ICD bag showed continuous bubbling and air
      entry remained absent on the right side. An urgent right thoracotomy was done
      which revealed right main bronchus tear; the tear was repaired using interrupted
      Prolene(r) sutures. Patient recovered well and was discharged 10 days later in a
      stable condition.

PMID- 29207779
TI  - Intraductal Tubulopapillary Neoplasm: A New Entity in the Spectrum of Pancreatic
      Intraductal Neoplasms.
AB  - Intraductal Tubulopapillary Neoplasms (ITPN) is a rare and new entity defined as
      an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-
      grade dysplasia and ductal differentiation without overt production of mucin. Its
      clinical presentation can be varied, which makes the diagnosis quite challenging.
      In this report, we present a case of pancreatic ITPN and review the published
      work to learn clinicopathological, radiological features and treatment strategies
      of this recently proposed pancreatic neoplasm.

PMID- 29207780
TI  - Autoimmune Pancreatitis Type II: First Report from India.
AB  - Autoimmune Pancreatitis (AIP) presents in two forms - Type I or lymphoplasmacytic
      sclerosing pancreatitis and Type II or idiopathic ducto-centric pancreatitis
      (IDCP). AIP II is rare in south Asia and, especially so, in India. Most patients
      have either Idiopathic Chronic Pancreatitis (ICP) or alcohol related chronic
      pancreatitis. AIP Type I has been described in India. We herein report a patient
      who had features of ICP on imaging, for whom surgery was performed to relieve
      chronic pancreatic pain. However, the pathologic features revealed AIP Type II or
      IDCP.

PMID- 29207781
TI  - A Boy with a Congenital Sagittal Fissure of the Glans Penis Representing an
      Abortive Isolated Urethral Duplication.

PMID- 29207782
TI  - Prediction of Delivery in Women with Threatening Preterm Labour using
      Phosphorylated Insulin-Like Growth Factor Binding Protein-1 and Cervical Length
      using Transvaginal Ultrasound.
AB  - Introduction: Preterm delivery remains a challenge in Obstetrics as it is
      responsible for significant cause of perinatal morbidity and mortality. At
      present there is no standard test for prediction of preterm labour for timely
      referral to a center with NICU facilities. Aim: To evaluate the effectiveness of
      the cervical phosphorylated insulin like growth factor binding protein-1(phIGFBP
      1), cervical length measurement and combination of phIGFBP-1 with cervical length
      for Predicting Preterm Labour (PTL). Materials and Methods: It was a
      observational prospective study done from January 2014 to April 2015 in
      Department of Obstetrics and Gynaecology, NDMC Medical College and Hindu Rao
      Hospital, Delhi, India. A total of 100 women with singleton pregnancy, between 24
      and 36 weeks of gestation with complaint of uterine contractions were randomly
      selected. These women were subjected to detect phIGFBP-1 in cervical secretions
      and cervical length measurement by Transvaginal Sonography (TVS). Result of the
      test, cervical length and time lapse between test and delivery was noted and the
      results were analysed. The cervical length less than 25 mm was used as a cut off
      point for predicting pre-term delivery. Data was analysed using SPSS software
      version 20.0. Results: The Negative Predictive Value (NPV) of phIGFBP-1 and
      cervical length was similar (95.2% vs 94.05%) respectively for prediction of
      preterm labour within one week of admission and 93.92% vs 94.80% at 37 weeks of
      gestational age. Combined test had higher NPV of 96.38% at 34 weeks of gestation
      and 94% within two days of admission. Positive Predictive Value (PPV) was low for
      both the test and combining the two-test did not have any advantage as far as PPV
      was concerned. Receiver Operating Characteristic (ROC) curve showed that the
      combined test had a superior result in predicting PTL compared to either phIGFBP
      1 or cervical length. The combined test had steepest ROC curve at < 34 weeks of
      gestation (AUC-0.83 with 95% CI). Conclusion: The phIGFBP-1 test and cervical
      length have an almost equivalent ability to predict preterm delivery
      independently. The combined use of phIGFBP-1 and TVS for cervical length shows an
      increase in efficacy in predicting preterm labour.

PMID- 29207783
TI  - Evaluation of Maternal and Perinatal Outcomes of Induction in Borderline
      Oligohydramnios at Term.
AB  - Introduction: Oligohydramnios is described as decreased amniotic fluid volume
      relative to gestational age. Semiquantitatively it is described using the
      Amniotic Fluid Index (AFI) which is calculated by adding the depth in centimetres
      of the largest vertical pocket in each of four equal uterine quadrants. AFI less
      than or equal to 5 cm is defined as oligohydramnios. A Borderline Oligohydramnios
      (BO) is defined as AFI 5.1-8 cm. Aim: To assess the maternal and perinatal
      outcome of induction in borderline oligohydramnios cases at term. Materials and
      Methods: This is a retrospective observational study done from December 2015 to
      November 2016 in Mahatma Gandhi Medical College and Research Institute,
      Puducherry, India. Fifty cases of BO with AFI 5.1 cm - 8 cm taken as case and
      another 50 cases of Normal Liquor (NL) with AFI 8.1 cm - 18 cm taken as control.
      Data was collected and analysed by SPSS software version 20.0 For qualitative
      data, the chi2-test or Fisher's-exact test were used and for continuous
      variables, the t-test was used. Results: Cases and controls were matched in
      baseline parameters. More number of cases were found with meconium stained liquor
      during labour which is statistically significant (p<0.05). Otherwise there were
      no statistical significant difference between cases and controls in maternal and
      perinatal outcome. Conclusion: Induction of labour in cases with BO cases
      compared to those with NL at term did not show very statistically significant
      difference in terms of induction to delivery interval and neonatal outcome.

PMID- 29207784
TI  - Emergency Peripartum Hysterectomy: A 14-Year Experience at a Tertiary Care Centre
      in India.
AB  - Introduction: Emergency Peripartum Hysterectomy (EPH), although relatively
      infrequent in present day obstetrics, is a life-saving procedure in the event of
      a massive postpartum haemorrhage. Aim: To assess incidence, risk factors,
      indications and complications of peripartum hysterectomies at a tertiary care
      teaching hospital in India. Materials and Methods: A retrospective study was
      conducted at 650-bedded tertiary care medical teaching hospital in Southern
      India. All emergency peripartum hysterectomies performed between February 2002
      and December 2015 at a tertiary care teaching hospital, were included in the
      study. Demographic characteristics, risk factors, antepartum, intrapartum and
      post-partum events, need for blood transfusion, length of stay in intensive care
      unit and postoperative complications were noted. Data was entered in Microsoft
      Excel spreadsheet and analysed using SPSS software version 22.0. For categorical
      variables, data was compiled as frequency and percent. For continuous variables,
      data was calculated as mean+/-SD. Results: Among 16,473 deliveries in the study
      period, 12 emergency peripartum hysterectomies were undertaken, the incidence
      being 0.073%. Women were aged 20 to 40 years (mean 30.25 years). Majority (83%)
      were multiparous women. Atonic postpartum haemorrhage was the most common (58%)
      indication for hysterectomy. About 67% of hysterectomies performed were subtotal
      hysterectomies. One half of them had a previous caesarean section. Two patients
      had bilateral internal iliac artery embolization for ongoing haemorrhage. All
      patients required intensive care and blood transfusion. Two patients did not
      survive even after hysterectomy. Conclusion: Atonic postpartum haemorrhage was
      the most common reason for performing an emergency peripartum hysterectomy. Women
      with previous caesarean section are at increased risk, both due to atonic and
      traumatic postpartum haemorrhage. Regular departmental audits are needed to
      formulate appropriate protocols to decrease mortality and near-miss events like
      EPH. Stringent protocols should be instituted for managing obstetric haemorrhage.
      Although EPH is life-saving, early intervention by a senior obstetrician well
      versed with conservative procedures may avoid morbidity associated with EPH.

PMID- 29207785
TI  - Role of Sonographic Gray-Scale Pattern Recognition in the Diagnosis of Adnexal
      Masses.
AB  - Introduction: Characterization of adnexal masses as benign or malignant is of
      utmost importance for optimal management and prognostication. Ultrasound
      examination plays an important role in the differentiation of adnexal masses.
      Various sonographic characteristics have been recognised to differentiate benign
      and malignant adnexal masses. Subjective evaluation of gray-scale ultrasound
      images by an experienced ultrasound examiner to discriminate adnexal masses is
      known as "pattern recognition". Aim: To access the efficacy of pattern
      recognition at predicting an accurate histological diagnosis of adnexal masses.
      Materials and Methods: All adnexal masses diagnosed clinically or during
      screening sonography were included in the study (n=136). Sonographic pattern
      recognition was performed and documented with specific diagnosis whenever
      feasible. Risk of Malignancy Index 3 (RMI3) score was also calculated. Results
      were compared with the gold standard histology. Chi-square test was used to
      assess the significance of the results and a p-value <0.05 was considered
      statistically significant. Results: In the final cohort of 136 women, on pattern
      recognition, 91 were suspected to have benign adnexal masses and 45 were reported
      as malignant adnexal masses. However, on final histo-pathology, 94 patients had
      benign tumours and 42 patients had malignant disease. The benign group pattern
      recognition could render a specific diagnosis in 85.7% as compared to RMI3
      pattern recognition conferred a sensitivity of 95.2% (RMI3 78.6%), with a slight
      compromise in the specificity (94.7% versus 96.8%). Conclusion: Pattern
      recognition is a sensitive and specific sonographic tool in discriminating benign
      and malignant adnexal masses. Moreover, it is also useful in differentiating
      various benign adnexal masses.

PMID- 29207786
TI  - Recurrent Vaginal Cuff Dehiscence in a Treated Case of Carcinoma Cervix.
AB  - Vaginal Cuff Dehiscence (VCD) is partial or total separation of anterior and
      posterior vaginal cuff layers. We report a case of recurrent vault cuff
      dehiscence in a patient of cervical carcinoma. A 60-year-old treated case of
      carcinoma cervix post surgery and radiotherapy was found to have vault dehiscence
      and intestinal prolapse second time during a routine speculum examination. She
      underwent an emergency laparotomy and closure of vault. Vaginal Cuff Dehiscence
      with Evisceration (VCDE) is a rare but potentially fatal complication following
      hysterectomy. Postoperative infection, poor technique, hematoma, coitus before
      healing, radiotherapy, corticosteroid therapy are the risk factors. Radiotherapy
      leads to progressive obliterative endarteritis and resultant tissue hypoxia.
      There is paucity of literature regarding the best management of VCD, but early
      corrective intervention is necessary. Patients and the treating physicians should
      be made aware of this possibility especially those receiving adjuvant radiation
      or cases of robotic or laparoscopic hysterectomies.

PMID- 29207787
TI  - Primary Adenocarcinoma of the Fallopian Tube: A Rare Entity.
AB  - Primary fallopian tube carcinoma is an uncommon gynaecologic malignancy usually
      seen in postmenopausal females. We present a case of a 66-year-old postmenopausal
      female who presented with complaint of blood mixed vaginal discharge on and off
      for past one month. Workup of the patient revealed no abnormality other than
      presence of atypical squamous cells on Papanicolaou (PAP) smear. MRI showed
      mildly bulky cervix with around 4cc fluid in endometrial cavity. As the patient
      remained symptomatic and fluid in endometrial cavity persisted, total abdominal
      hysterectomy with bilateral salpingo-oophorectomy was done. On histopathological
      examination, fimbrial end of left tube had features of poorly differentiated
      papillary serous adenocarcinoma. Postoperatively, she was given chemotherapy and
      is doing well with more than 3 years of follow up. This case highlights the
      importance of high suspicion in postmenopausal women with bleeding per vaginum,
      where there is little to suggest clinically or radiologically.

PMID- 29207788
TI  - Hyperparathyroidism during Pregnancy- A Diagnostic and Therapeutic Challenge.
AB  - Primary Hyperparathyroidism (PHP) is a rare event in pregnancy; Maternal
      complications in PHP patients can be as high as 67%. It can be overlooked easily
      because of many similar complaints shared by hyperparathyroidism and pregnancy
      such as nausea and vomiting, gastritis, bone aches, easy fatigability.
      Hypercalcemic crisis can develop resulting in coma and death. Neonatal effects
      are tetany and death in about 80% of cases. We report a case, of an antenatal
      woman at 30 weeks gestation with complains of painful swelling in left lower jaw
      and below right knee, pain over right hip joint and frequent episodes of
      gastritis. She was finally diagnosed to have primary hyperparathyroidism and
      brown tumour due to parathyroid adenoma. The baby was kept in Neonatal Intensive
      Care Unit (NICU) for three weeks, in view of prematurity with respiratory
      distress and later developed sepsis with DIC. The patient's signs and symptoms
      regressed after parathyroid surgery and the baby was healthy at the time of
      discharge. This case highlights the progressive deterioration of the patient
      because of lack of awareness of this disease process and its impact on maternal
      and foetal morbidity.

PMID- 29207789
TI  - Minerals in Pregnancy and Lactation: A Review Article.
AB  - Micronutrients (include vitamins and minerals) are essential for normal function,
      growth and development. Minerals have important effects on the health of the
      mother and foetus. But biological mechanisms of minerals are not completely
      understood. Micronutrient deficiency during pregnancy can lead to anaemia,
      hypertension, obstetric complications and even maternal death and in foetus lead
      to a fail in growth and development. Mineral deficiency during pregnancy,
      particularly exist in developing countries. During pregnancy due to the increased
      demands caused by physiological changes, deficiency is exaggerated and as a
      result its complications occur. Thus, ensuring to receive enough macronutrients
      and micronutrients before and during pregnancy, is important. Nevertheless, there
      are controversies regarding administrating supplements. There are not enough
      studies about some of the minerals and the challenges remain. Regarding the
      importance of minerals in pregnancy and lactation, in this review we will analyze
      the role of them in pregnancy and lactation.

PMID- 29207790
TI  - Large Vulvar Haematoma of Traumatic Origin.

PMID- 29207791
TI  - Gastroenteritis In Pregnancy: Relevance and Remedy.

PMID- 29207792
TI  - Clinical Evaluation of Efficacy and Performance of All-Poly Tibial Freedom(r)
      Total Knee System for Treating Osteoarthritis Patients: Three-Year Follow Up
      Study.
AB  - Introduction: Advancement in technology in terms of design and building materials
      has made Total Knee Replacement (TKR) a highly effective, safe, and predictable
      orthopedic procedure. Aim: To review the clinical outcomes for efficacy and
      performance of Freedom Total Knee System for the management of Osteoarthritis
      (OA), at a minimum of three years follow up. Materials and Methods: For this
      retrospective, post-marketing study, clinical data of patients treated with
      Freedom Total Knee System was retrieved from the clinical records after approval
      from the Institutional Ethics Committee . All the patients above the age of 18
      years who completed at least three years after TKR were observed for the study
      purpose. Patients treated for OA were included while the patients who received
      the implant for treatment of rheumatoid arthritis and traumatic injury were
      excluded. Factors such as aseptic loosening, implant failure, and need for
      revision surgery were observed to evaluate implant performance. Cases were
      recruited for clinical assessment of primary efficacy endpoint in terms of post
      surgery maximun range of motion. Secondary efficacy endpoint was to determine the
      clinical and social quality of life as per the American Knee Society Score (AKSS)
      and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain
      and stiffness scores. Results: A total of 158 patients who had 191 TKR were
      observed for performance. The mean age of the patients was 67.67 years; mean BMI
      was 28.97+/-3.33, and the group comprised of 43% men and 57% women. Telephonic
      follow up at three years of 158 patients identified that none of them required
      revision surgery or had aseptic loosening suggesting excellent performance. Final
      clinical follow up at three years was available for only 35 patients (41 knee
      implants). The range of motion significantly improved from preoperative 104
      degrees +/-5.67 degrees  (range, 85 degrees -119 degrees ) to 119.8 degrees +/
      11.05 degrees  (98 degrees -123 degrees ) at follow-up (p<0.05). There was a
      significant improvement in clinical and functional AKSS score and WOMAC score at
      follow-up. Conclusion: The evaluation of Freedom Total Knee System for TKR in
      treating OA, at a minimum of three years follow up showed excellent outcomes in
      terms of performance, range of motion, reduced postoperative stiffness and pain,
      and improved functionality.

PMID- 29207793
TI  - Posterior Dislocation of Subtalar Joint without Associated Fracture: A Case
      Report and Review of Literature.
AB  - Posterior subtalar dislocation is an exceedingly rare entity. Clinically, the
      appearance of the foot can simulate a complex fracture dislocation. It is
      important to recognize that not all posterior subtalar dislocations are true
      posterior dislocations. We report a true posterior subtalar dislocation in a 34
      year-old female, managed promptly with closed reduction and resulting in an
      excellent functional outcome. A chronic dislocation or an irreducible dislocation
      may need open reduction.

PMID- 29207794
TI  - Non Traumatic Fracture of Pedunculated Osteochondroma: Conservative Management of
      a Rare Case.
AB  - Fracture of a pedunculated osteochondroma is a rare complication for which
      surgical treatment is usually advocated. In this report, we present the
      functional and radiological outcomes of a case of a conservatively treated
      fracture of a pedunculated osteochondroma. A 26-year-old man with no history of
      trauma presented with acute onset of left knee pain, oedema, and limited range of
      motion. Radiological assessment revealed a fracture of a pedunculated
      osteochondroma. It was treated conservatively with an elastic bandage and non
      steroidal anti-inflammatory drugs, and union was achieved by the 12-week follow
      up, with no complications. Although surgical treatment is usually advocated for a
      pedunculated osteochondroma fracture, conservative treatment should be the first
      approach to avoid complications of surgical intervention.

PMID- 29207795
TI  - Association between Vascular Endothelial Markers and Carotid Intima-Media
      Thickness in Children and Adolescents with Type 1 Diabetes Mellitus.
AB  - Introduction: Type 1 Diabetes Mellitus (T1DM) is one of the important risk factor
      for cardiovascular disease. Endothelial dysfunction and increased Carotid Intima
      Media Thickness (CIMT) result in cardiovascular complications. Vascular Cell
      Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) are
      two adhesion molecules that are markers of early atherosclerosis and play a
      significant role in developing atherosclerosis. Aim: To evaluate CIMT and its
      association with the levels of ICAM-1 and VCAM-1 in children and adolescents with
      T1DM. Materials and Methods: In this descriptive, cross-sectional study conducted
      between April 2013 and September 2014, 29 children aged 7-20 years with T1DM for
      at least two years and 29 age and sex-matched, healthy individuals were
      evaluated. Plasma level of ICAM-1 and VCAM-1 was measured by ELISA, and CIMT via
      Doppler ultrasound was also assessed. The data were analysed by t-test and
      Pearson's correlation coefficient in SPSS 16.0 (p<=0.05). Results: Independent t
      test indicated that there is a significant difference in ICAM-1 level between the
      patients and controls (p<0.001). Further, CIMT was significantly higher in
      diabetic subject (p<0.001). CIMT was not significantly associated with the level
      of VCAM-1 and ICAM-1 in the patients (p>0.5). Conclusion: ICAM-1 and VCAM-1 were
      not associated with CIMT but, CIMT and level of ICAM-1 were significantly, higher
      in diabetic patients, and therefore could be used as useful tools for
      identification of early atherosclerosis in children and adolescents with T1DM.

PMID- 29207796
TI  - Clinico-Aetiological Study of Severe and Very Severe Pneumonia in Two Months to
      Five Years Children in a Tertiary Health Care Centre in Odisha, India.
AB  - Introduction: Pneumonia is a major cause of mortality under five-year-old
      children. In spite of recent advances in management, there is paucity of data on
      clinical, aetiological profile of severe and very severe pneumonia among under
      five-year-old children in developing countries. Aim: To determine the clinico
      aetiological factors of severe and very severe pneumonia and its outcome in
      children aged two -months to five-years in a tertiary health care centre in
      Odisha, India. Materials and Methods: This was a prospective observational study.
      All the patients between two-months to five-years age admitted to SCB Medical
      College, Cuttack, Odisha, India, were screened for features of severe and very
      severe pneumonia based on WHO diagnostic criteria, over a one year period. Out of
      10300 patients admitted to our hospital during the study period; 141 cases were
      included in the study. Their clinical parameters were recorded and were followed
      up till discharge or death. Continous variables were analyzed using Student t
      test or Mann-Whitney U test whereas categorical data were analyzed using Pearson
      Chi square test or Fischer Exact test. Results: Out of 141 patients included in
      the study, cough, tachypnea and chest retractions were present in 100% cases
      while fever in 97.1% (137) cases. In 17% (24) cases, bacterial pathogen was
      isolated. Most common organism being Staphylococcus aureus 8.51% (12) followed by
      Streptococcus pneumonie 6.4% (9). Higher mortality 11.34% (16) was found among
      patients presenting after three days of illness (p=0.048). About 17% (24)
      patients developed complications. Common complications were sepsis 5.6% (8), CCF
      4.2% (6) and empyema 4.2% (6). Higher mortality 22 (15.6%) was observed in very
      severe pneumonia group (p=0.003). Conclusion: The incidence of severe and very
      severe pneumonia was higher in infancy. Rainy and winter season were associated
      with higher incidence of disease. Bottle feeding practice and smoking were
      significantly associated with more severe disease. Death rate was high among
      patients admitted to hospital after three days of onset of illness, so early
      referral is indicated for better outcome.

PMID- 29207797
TI  - Audit of Organic Acidurias from a Single Centre: Clinical and Metabolic Profile
      at Presentation with Long Term Outcome.
AB  - Introduction: Organic Acidurias (OA) accounts between 10% and 40% of confirmed
      Inborn Errors of Metabolism (IEM) in India. With prompt recognition and
      management, better survival but adverse neurodevelopmental outcome is reported.
      Aim: To study the clinical and metabolic presentation, management with immediate
      and long term outcome of symptomatic children with confirmed OA. Materials and
      Methods: Hospital based study of symptomatic children diagnosed to have OA
      between 2003 and 2009 and the survivors followed up over next five years.
      Diagnosis was based on clinical and metabolic presentation and confirmed by
      spectrometry analyses of urine and blood. Management, immediate outcome,
      compliance to treatment and recurrence of crises were documented.
      Neurodevelopmental outcome was assessed in follow up. Mean with Standard Error
      (Mean +/- SE) and frequencies with percentages were calculated. Results: Of 72
      cases suspected to have IEM, 38 (52.8%) were confirmed of (IEM), and out of which
      15 (39.5%) had OA. Methyl malonic acidemia, multiple carboxylase deficiency and
      Propionic Acidemia (PA) constituted the largest proportion. Neurodevelopmental
      issues (73.3%) and metabolic crisis (53.3%) were common presenting features. Mean
      +/- SE of ammonia was 639.0+/-424.1 MUg/dl and lactate was 33.6+/-4.9 mg/dl. Mean
      pH, bicarbonate, and anion gap was 7.27+/-0.07, 14.1+/-2.3 and 17.9+/-2.3
      respectively. Management was protocol based. Death was reported in two cases of
      PA; other morbidities were seen in five. Recurrent crisis (46.7%) complicated the
      follow up in survivors. Spasticity, extrapyramidal movement disorder,
      intellectual subnormality, autism spectrum, attention deficit hyperactivity
      disorder and sensory neural deafness were seen amongst survivors, in spite of
      compliance to therapy. Conclusion: OA is part of differential diagnosis in sick
      children and treatment needs to be prompt and specific. Prognosis is guarded even
      with long term cofactor supplementation in the symptomatic.

PMID- 29207798
TI  - Does Vitamin D Supplementation Improve Glycaemic Control In Children With Type 1
      Diabetes Mellitus? - A Randomized Controlled Trial.
AB  - Introduction: Vitamin D endocrine system is a potential immune system modulator
      and has been implicated in the pathogenesis of several autoimmune diseases
      including Type 1 Diabetes Mellitus (T1DM). Studies have demonstrated an inverse
      risk relationship between T1DM and Vitamin D levels and also, shown a reduced
      risk of the disease with its supplementation. Aim: To evaluate the role of
      Vitamin D as an adjuvant in improving glycaemic control and residual pancreatic
      beta-cell function. Primary outcome was the mean change in HbA1c levels over a
      period of six months. Materials and Methods: This double-blinded randomized
      controlled trial was done in a tertiary care hospital, Southern India and
      included 52 children aged 1-18 years with T1DM, with 26 participants each in the
      intervention and standard of care arm. Oral Vitamin D therapy was administered
      once a month for six months in addition to insulin in intervention arm while only
      insulin was continued for other arm. Plasma HbA1c, serum 25-Hydroxy vitamin D
      (25OHD), insulin dose and C-peptide were measured at baseline and repeated after
      6 months. Results: Prevalence of Vitamin D deficiency was as high as 63.5% i.e.,
      33 of total 52 children with T1DM. The mean C-peptide levels were significantly
      high in intervention arm as compared to standard of care after six months.
      However, there was no significant difference in HbA1c, and insulin requirement at
      six months between the two groups. No adverse events due to Vitamin D therapy
      were noted. Conclusion: Oral Vitamin D may serve as an adjuvant to insulin
      therapy for children with T1DM by augmenting residual beta-cell function and
      improving insulin secretion. However, a significant decrease in HbA1c level and
      requirement for exogenous insulin was not achieved in our study.

PMID- 29207799
TI  - Change in Bone Mineral Density and Role of Vitamin D and Calcium Supplementation
      During Treatment of First Episode Nephrotic Syndrome.
AB  - Introduction: Nephrotic Syndrome (NS) is one of the common illnesses in
      childhood. Oral glucocorticoids are mainstay of treatment, which are known to
      cause various short term and long term adverse effects including osteoporosis.
      Children with first episode and infrequent relapsing NS are not prescribed
      Calcium (Ca) and Vitamin D (VitD) supplements routinely. Aim: To observe change
      in Bone Mineral Density (BMD) in children during first episode of NS and role of
      VitD and Ca supplementation during the treatment of first episode of NS.
      Materials and Methods: A double blind randomized control trial was conducted in
      Department of Paediatrics at a tertiary care center in New Delhi, India, from
      October 2011 to March 2013. Three groups were made, each having sample size of
      20. Group A (intervention group) consisted of first episode NS patients who
      received steroids along with VitD and Ca supplements. Group B (placebo group) had
      children with first episode of NS treated with steroids and placebo. Biochemical
      tests and BMD assessment were done at start and after three months of steroid
      treatment. Groupwise differences in BMD, VitD, Ca, Phosphate (PO4) and Alkaline
      Phosphatase (ALP) were assessed at baseline and after three months through
      Analysis Of Variance (ANOVA). Linear regression models for repeated measures were
      used to test the association between different variables and BMD and also between
      various study groups. Results: Among study population, Group B had significant
      decrease in VitD levels (28.85+/-5.52 ng/dl to 14.22+/-1.36 ng/dl) than to Group
      A (23.59+/-6.08 ng/dl to 13.27+/-1.35 ng/dl) after three months of steroid
      treatment. Similarly BMD decreased significantly in Group B (-0.033g/cm2) as
      compared to Group A (0.001g/cm2) showing significant decrease in VitD and BMD in
      children with first episode of NS after three months of steroid treatment whereas
      use of VitD and Ca supplements improves the deficit. Conclusion: Ca and VitD
      supplement should be used during treatment of first episode of NS, but further
      studies are required to ascertain the adequate dose for the same.

PMID- 29207800
TI  - Right Pulmonary Venous Atresia: A Rare Cause for Recurrent Unilateral Pneumonia.
AB  - Recurrent unilateral pneumonia poses a diagnostic dilemma for all paediatricians.
      Isolated pulmonary venous atresia is an uncommon entity, which presents with
      recurrent unilateral pulmonary infections, dyspnoea on exertion and haemoptysis.
      It is associated with significant mortality and morbidity. Owing to rarity of
      condition, there may be some difficulties in the diagnosis and therapy. Pulmonary
      angiography is the investigation of choice. However, the current multislice CT
      scanners may obviate the need for pulmonary angiography. We report a two-year-old
      child with this rare congenital malformation and discuss diagnostic modalities
      and management options.

PMID- 29207801
TI  - Autoimmune Haemolytic Anaemia-A Spectrum of Presentation in Children.
AB  - Autoimmune Haemolytic Anaemias (AIHAs) are rare in children. They can be either a
      primary disease or secondary to/triggered by a host of other clinical conditions.
      We present five interesting cases of paediatric AIHA associated with infections
      (viral, bacterial and atypical) and autoimmune diseases {Systemic Lupus
      Erythematosus (SLE) and Autoimmune Hepatitis (AIH)}. The H1N1 influenza
      associated AIHA responded to oseltamivir and Intravenous Immunoglobulin (IvIg)
      while the cases secondary to Mycoplasma pneumoniae and pneumococcal bacteraemia
      required only treatment of the primary infection. AIHA with SLE responded well to
      corticosteroid therapy but the patient with AIH and AIHA succumbed to severe
      liver failure. Rest of the four cases with good response to therapy did not have
      any recurrence/relapse of AIHA during their follow up periods.

PMID- 29207802
TI  - Image Findings of Solid Pseudopapillary Neoplasms of the Pancreas on Multiphasic
      Multidetector CT Scan-A Single Institute Experience from Southern India.
AB  - Introduction: Solid Pseudopapillary Neoplasms (SPN) are uncommon pancreatic
      tumours and are slow growing with uncertain malignant potential, showing female
      preponderance. Postoperative prognosis is good and metastasis is rare. Aim: To
      summarise the imaging and pathological features of seven cases of SPN in three
      years period, from January 2013 to January 2016. Materials and Methods: In this
      retrospective study the imaging features of seven cases on triphasic
      multidetector Computed Tomogram (CT), a 16-slice scanner, were reviewed along
      with CT-guided Fine Needle Aspiration Cytology (FNAC) and histopathological
      examination. Statistics were expressed in terms of percentiles. Results: All
      cases were female patients with an age range of 13-35 years (mean: 23.3 years).
      On CT assessment, the size of the tumours varied from 2.5-14 cm (mean: 5.3 cm).
      All these tumours were well capsulated and round to oval in shape. In four out of
      seven cases, the tumour was located in the tail of pancreas. All the solid
      enhancing portions showed moderate enhancement of at least 20-30 HU compared to
      unenhanced scan, on the other hand the cystic parts remained unenhanced with <5
      HU variation in comparison to the plain scan. Histopathological examination
      exhibited characteristic poorly cohesive cuboidal cells arranged in papillaroid
      pattern having fine nuclear chromatin with nuclear grooves. Conclusion: Solid
      pseudopapillary neoplasm is a high diagnostic possibility in case of a young
      female having pancreatic mass and needs to be evaluated with triphasic contrast
      enhanced CT scan, followed by FNAC and or histopathological examination.

PMID- 29207803
TI  - Radiological Manifestations of Pulmonary Tuberculosis - A Comparative Study
      between Immunocompromised and Immunocompetent Patients.
AB  - Introduction: Pulmonary tuberculosis has atypical radiological manifestations in
      patients with underlying immunocompromised disease like diabetes and human
      immunodeficient virus infection. Computed tomography has important role in such
      patients for early diagnosis of disease and management to minimize complication.
      Aim: To evaluate and compare the computed tomography chest features of pulmonary
      tuberculosis in between immunocompromised patients and immunocompetent patients.
      Materials and Methods: This cross-sectional study was conducted in the hospital
      on newly diagnosed 60 pulmonary tuberculosis patients of which 30 patients had no
      underlying disease (Immunocompetent Group) and 30 patients had diabetes mellitus
      or were human immunodeficiency virus seropositive (Immunocompromised Group). CT
      scan of chest were evaluated for each patient. Results: In immunocompetent
      patients, 36.7% had radiologically atypical presentation,90% had nodular
      opacities, 73.3% had consolidation, 23.3% had lymphadenopathy, 60% had cavitation
      and cavitatory lesion were single in 94.4% patients. Isolated upper lung field
      were involved in 60% patients. In immunocompromised patients 76.7% had
      radiologically atypical presentation, 66.7% had nodular opacities, 46.7% had
      consolidation, 63.3% had lymphadenopathy, 20% had cavitation and cavitatory
      lesions were multiple in 60% patients. Isolated lower lung field were involved in
      23.3% patients. Conclusion: We concluded that immunocompromised patients have
      more atypical involvement of lung fields, higher prevalence of lymphadenopathy as
      compared to immunocompetent patients. Diabetic patients have multiple cavitatory
      lesions as compared to non-diabetic patients. HIV seropositive patients have more
      prevalence of lymphadenopathy as compared to HIV seronegative patients.

PMID- 29207804
TI  - An Evaluation of Dental Crowding in Relation to the Mesiodistal Crown Widths and
      Arch Dimensions in Southern Indian Population.
AB  - Introduction: With the advancement in imaging technology, 3D dental computed
      tomography plays a very significant role in orthodontic treatment and diagnosis.
      Aim: To evaluate dental crowding in relation to the mesiodistal crown widths and
      arch dimensions and also to determine the differences of dental crowding among
      males and females, in Southern Indian population. Materials and Methods: A total
      of 132 subjects were divided into two groups: crowded and non-crowded, each
      comprising 66 subjects (33 males and 33 females), aged between 15 and 35 years,
      who were referred for computed tomography scan of brain to the radiology
      department, were selected. During the scan both the jaws were included in the
      image. The 2D images were converted to 3D images using volume rendering software.
      By using measurement tool, individual and collective mesiodistal crown widths of
      canine, first and second premolar and first molar and arch perimeter of both the
      maxillary and mandibular jaws were measured. Results: When both the gender were
      considered, the mesiodistal crown widths and arch perimeter were statistically
      significant for dental crowding in both mandibular jaw (p-value=0.001 for both
      mesiodistal crown width and arch perimeter) and maxillary jaw (p-value=0.016 for
      mesiodistal crown width and 0.002 for arch perimeter). However, when analysed
      separately, in males the mesiodistal crown widths and arch perimeter were
      statistically significant for dental crowding in both mandibular jaw (p
      value=0.001 for mesiodistal crown width and 0.002 for arch perimeter) and
      maxillary jaw (p-value=0.002 for mesiodistal crown width and 0.001 for arch
      perimeter) but in females it was not statistically significant in any jaw (p
      value=0.7 for mesiodistal crown width and 0.06 for arch perimeter in mandibular
      jaw and p-value=0.2 for mesiodistal crown width and 0.9 for arch perimeter for
      maxillary jaw). The crowded group had larger tooth size and smaller arch
      perimeter. Conclusion: This study concluded that in males, both the factors i.e.,
      mesiodistal crown width and arch dimensions contributed to dental crowding and
      the crowded dentition had larger mesiodistal tooth size and smaller arch
      dimensions; whereas, in females both the factors were not responsible for
      crowding in Southern Indian population.

PMID- 29207805
TI  - Benign Lesions on Screening Mammography: Increasing Diagnostic Confidence in a
      Hitherto Unscreened Population.
AB  - Introduction: Screening mammography is used for detection of breast cancer and is
      interpreted using the Breast Image Reporting and Data System (BIRADS) convention.
      It is not routinely offered to women in countries which do not have a national
      screening programme resulting in a challenge for the radiologist who has to
      interpret these in the absence of previous mammograms. Aim: To analyse benign and
      probably benign lesions in screening mammograms in a hitherto unscreened
      population and suggest protocols to increase diagnostic confidence. Materials and
      Methods: Screening mammograms of 362 asymptomatic women in the age range of 40 to
      60 years carried out over a two year period were retrospectively analysed.
      Patients of breast cancer and those who had palpable lumps were excluded from the
      study. All images were analysed in standard Mediolateral Oblique (MLO) and
      Craniocaudal (CC) projections with additional views wherever necessary.
      Corroborative ultrasound had been carried out wherever indicated in the opinion
      of the interpreting radiologist. The mammograms were finally classified according
      to the BIRADS convention. Results: Of the total number of 362 women screened,
      most of whom did not have any previous mammogram, 162 were reported as BIRADS I,
      179 as BIRADS II and 18 as BIRADS III. The mammograms reported as BIRADS II had
      various findings including dystrophic calcification/macrocalcification, vascular
      calcification, simple cysts and fibroadenomas. Only 26 (16.04%) of the BIRADS I
      mammograms had undergone further evaluation with Ultrasound (US) due to dense
      breasts or asymmetrical involution of breast tissue whereas 76 (42.5%) of the
      BIRADS II mammograms had undergone further evaluation with US to characterize
      lesions like cysts and fibroadenomas, but occasionally also for benign clustered
      calcification. Of BIRADS III mammograms, 12 (66.6%) had required US correlation
      to exclude a mass in cases with dense breasts. The increased likelihood of
      ultrasound corroboration in BIRADS II and BIRADS III was analysed using the Chi
      square test and was statistically significant. Conclusion: In the absence of
      previous screening mammograms, a small number of BIRADS I mammograms and a
      significant number of BIRADS II and BIRADS III mammograms undergo a corroborative
      US examination. The addition of supplemental US to the evaluation of these
      lesions increase diagnostic confidence and lesion characterization in a
      population which is not subject to routine screening.

PMID- 29207806
TI  - Rapunzel Syndrome.
AB  - A bezoar refers to a mass of undigestible foreign material found in the
      gastrointestinal tract, mainly stomach. The second most common bezoar is the
      trichobezoar, which usually occurs in the young psychiatric female patients with
      history of trichotillomania and trichophagia. This is a case report of a 12 -year
      old female patient came with complaints of diffuse abdominal pain, vomiting, and
      constipation. Ultrasound, Barium X-ray and Computed Tomography scan were done,
      which suggested trichobezoar. Thus, trichobezoar should be considered as
      differential diagnosis of abdominal pain in young female patients with associated
      psychiatric complaints. A review is presented here, as a high index of suspicion
      for better diagnostic facilities which can help in timely diagnosis and
      intervention, to prevent further complications like intestinal obstruction,
      perforation and mortality in such children.

PMID- 29207807
TI  - Epididymal Cystic Lymphangioma Presenting as Scrotal Swelling in a Post Surgery
      Case of Carcinoma Rectum- A Case Report.
AB  - Cystic lymphangiomas are usually congenital malformations of draining lymphatic
      channels with most common sites including neck, axilla, mediastinum and
      retroperitoneum. Occurrence of lymphangiomas in scrotum or inguinal region is a
      rare entity and epididymal origin of these lesions is even more infrequent. We
      herein report a case of epididymal lymphangioma detected on USG, which developed
      after surgical abdominal lymph nodal dissection in an adult patient of carcinoma
      rectum presenting as painless scrotal swelling.

PMID- 29207808
TI  - Chilli Sign: Pathognomonic Sign for Ruling Out Sacral Agenesis on Foetal MRI.

PMID- 29207809
TI  - Therapeutic Efficacy of Ozone Injection into the Knee for the Osteoarthritis
      Patient along with Oral Celecoxib and Glucosamine.
AB  - Introduction: Suffering from osteoarthritis is prevalent among elderly patients
      so the use of intra-articular injection of medical ozone may well be the
      effective way to relieve their pain. Aim: To evaluate the effect of intra
      articular injection of medical ozone given into the knee of the osteoarthritis
      patients, and to compare it with taking celecoxib and glucosamine orally.
      Materials and Methods: In the present study, 76 patients suffering from
      osteoarthritis were randomly assigned into two groups. In the ozone group, 20 ml
      ozone-oxygen mixture gas concentration of 20 MUg/ml was injected into knee
      articular cavity and each patient took oral celecoxib and glucosamine
      hydrochloride. Patients in control group only took the celecoxib and glucosamine
      hydrochloride orally.Pain score and Lysholm knee score were measured prior to the
      injection (pretreatment) and at one, three, six weeks after the beginning of the
      treatment (posttreatment). Results: After the treatment, the pain intensity and
      function significantly improved in the two groups compared with the pretreatment
      (p<0.05). In the ozone group, three weeks after intervention, the pain score
      improved significantly when compared with the control group (p<0.05).After the
      treatment, the lysholm scores increased significantly (p<0.05), but in the ozone
      group, it improved faster. Conclusion: Intra-articular injection of ozone plus
      oral celecoxib and glucosamine could significantly decrease pain intensity in
      patients with mild to moderate Knee Osteoarthritis (KOA), and improve their
      functional status early than oral celecoxib and glucosamine only.

PMID- 29207810
TI  - Comparative Study of the Effect of Dexmedetomidine Vs. Fentanyl on Haemodynamic
      Response in Patients Undergoing Elective Laparoscopic Surgery.
AB  - Introduction: Dexmedetomidine and fentanyl, both have sedative and analgesic
      effects. They are often used as adjunct during anaesthesia to attenuate pressor
      response during tracheal intubation. Limited study has been done comparing the
      effect of both drugs on haemodynamic response in patients undergoing laparoscopic
      surgery. Aim: The study was designed to compare the effect of dexmedetomidine Vs
      fentanyl on haemodynamic response to tracheal intubation, following
      pneumoperitoneum and intraoperative period in patients undergoing laparoscopic
      surgery. Materials and Methods: Sixty patients of age group 18-60 years of either
      sex, classified as American Society of Anaesthesiologist (ASA) Grade I and II
      undergoing elective laparoscopy surgery were randomly allocated to one of the two
      groups (Group-D) and (Group F) of 30 each. Group D received dexmedetomidine and
      Group F received fentanyl. Patients received intravenous 0.5 MUg/kg of the study
      drug as loading dose over 10 minutes prior to intubation followed by 0.2-0.7
      MUg/kg/hr as infusion till surgery was over. In operating room parameters like
      Heart Rate (HR), Respiratory Rate (RR), Systolic Blood Pressure (SBP), Mean
      Arterial Pressure (MAP), SpO2, EtCO2 were recorded 10 minutes after infusion of
      drug i.e., dexmedetomidine or fentanyl. The said parameters were again recorded
      after injection of induction drugs, after intubation, five minutes after
      intubation, just after pneumoperitoneum, and 5,10,15,30,45 and 60 minutes after
      pneumoperitoneum, five minutes after release of pneumoperitoneum, five and 10
      minutes after extubation. Results: Dexmedetomidine significantly attenuates
      stress response at intubation with lesser increase in HR (5% Vs 18%), SBP (9% Vs
      19%) and DBP (3% Vs 15%), MAP (2% Vs 15%) as compared to fentanyl (p<0.05).
      Throughout intraoperative period of pneumoperitoneum Group D showed significant
      fall in HR, SBP, DBP, MAP from baseline value at all points of time intervals
      whereas it remained constantly high above baseline value in Group F (p-value
      <0.05). Conclusion: Dexmedetomidine when compared to fentanyl causes greater
      attenuation of stress response to tracheal intubation, following pneumoperitoneum
      and in intraoperative period resulting in greater reduction of HR, SBP, DBP, MAP
      than that of fentanyl, thus causing better haemodynamic stability in patients
      undergoing elective laparoscopic surgery.

PMID- 29207811
TI  - Comparative Evaluation of Ropivacaine and Fentanyl Versus Ropivacaine and
      Fentanyl with Clonidine for Postoperative Epidural Analgesia in Total Knee
      Replacement Surgery.
AB  - Introduction: Clonidine an alpha 2 adrenoceptor agonist possesses analgesic
      properties and has been used as an adjuvant in epidural analgesia. The addition
      of clonidine to other analgesics may result in enhanced analgesia through
      additive mechanisms or synergistic mechanisms. The enhanced analgesia may lead to
      a decrease in the dosage of analgesic drugs along with reduction of side effects.
      Aim: The purpose of this study was to evaluate the effect of adding clonidine to
      epidural ropivacaine and fentanyl mixture in terms of quality of analgesia and
      side effects in patients of total knee replacement surgery. Materials and
      Methods: A prospective randomised double blind study was conducted on 60 patients
      of ASA physical status I, II and III who underwent unilateral total knee
      replacement surgery under combined spinal epidural anaesthesia. Patients were
      divided into two Groups A and B randomly. Postoperatively Group A received
      continuous epidural infusion of ropivacaine 2 mg.ml -1 and fentanyl 2 MUg.ml -1
      along with clonidine 2 MUg.ml-1 in the range of 3-7 ml.hr-1 while Group B
      received the ropivacaine and fentanyl epidural solution. The postoperative VAS
      scores, haemodynamic parameters, motor block, sedation, nausea, vomiting and any
      other significant side effects were noted. The two groups were compared with
      student's t-test, Pearson's Chi square test and t-test using SPSS statistical
      software. Results: Visual analog scale scores were lower in Group A (3.38) than
      in Group B (3.72). The average infusion rate was lower in Group A (4.7 +/- 0.7
      ml.hr -1) than in Group B (5.5 +/- 0.7 ml.hr-1). Patients in Group A required
      less dosage of rescue pain medication Paracetamol (1g i.v.), diastolic pressure
      and heart rate were lower in Group A. The groups were comparable in terms of
      sedation, motor block and nausea vomiting. Conclusion: Clonidine added to a
      ropivacaine and fentanyl mixture augmented the postoperative epidural analgesia
      without significant side effects.

PMID- 29207812
TI  - Prediction of Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)
      after Thoracic Surgery- The Role of Estimated GFR.
AB  - Introducton: Little is known about the prognostic utility of preoperative
      estimated GFR (eGFR) on perioperative Major Adverse Cardiovascular and
      Cerebrovascular Events (MACCE) in apparently lower risk patients undergoing
      moderate risk surgeries like thoracotomy. Aim: The current study sought to
      identify a clinically relevant cut-off value of eGFR for identifying thoracotomy
      patients at higher risk for MACCE. Materials and Methods: Between July 2012 and
      July 2016, 436 consecutive patients were retrospectively studied after elective
      thoracotomy in a single institution. Patients were classified into six groups
      according to the calculated Chronic Kidney Disease Epidemiology Collaboration
      equations (CKD-EPI) eGFR (ml min -11.73 m -2): Stage 1, eGFR >90; Stage 2,
      eGFR=60-89.9; Stage 3a, eGFR=45-59.9; Stage 3b, eGFR=30-44.9; Stage 4, eGFR=15
      29.9; Stage 5, eGFR <15. All the eGFR groups were analysed for perioperative
      MACCE, length of hospital stay, and mortality. Results: The incidence of
      perioperative MACCE in our study was 4.24%. The mean eGFR in our study as
      calculated by the CKD-EPI equation was 83 ml min-11.73 m-2. With the exception of
      nonfatal cardiac arrest which was not seen in any patient, the incidence of all
      MACCE increased with progressively worsening preoperative eGFR.It was seen by
      logistic regression analysis that the occurrence of any perioperative MACCE
      increased significantly with worsening eGFR (p<0.001). The increase in MACCE was
      particularly marked from Stage 3b onwards to the later stages (OR 1.9 in 3a vs.
      3.6 in 3b). The two mortalities observed in the study were in Stages 4 and 5 with
      no deaths seen in the better eGFR subgroups. There was also an increased length
      of hospital stay with declining eGFR. Conclusion: Preoperative eGFR is a
      predictor of perioperative MACCE in homogenous moderate risk elective surgical
      population like thoracic surgeries. There is an inverse relationship between eGFR
      and MACCE, particularly manifested at eGFR values <45 ml/min/1.73. Routine use of
      preoperative eGFR for cardiovascular and cerebrovascular risk assessment in
      patients undergoing moderate risk surgeries like thoracotomy would be beneficial.

PMID- 29207813
TI  - Anaesthetic Considerations for Balloon Mitral Valvuloplasty in Pregnant Patient
      with Severe Mitral Stenosis: A Case Report and Review of Literature.
AB  - Even though, the incidence of Mitral Stenosis (MS) has reduced grossly, it still
      remains a health problem in developing countries and is the most common rheumatic
      valvular lesion encountered in pregnant patients. The already compromised cardiac
      status of a pregnant female deteriorates further by the presence of MS. So,
      pregnancy is a common situation during which untreated and frequently poorly
      tolerated MS are first diagnosed. Percutaneous Balloon Mitral Valvuloplasty (BMV)
      may be life saving in such a setting and a multidisciplinary approach in the
      management reduces the mortality and morbidity during the procedure. Anaesthetic
      management of such a procedure has hardly ever been reported. We report a case of
      a 23-year-old woman presenting at 28 weeks gestation with severe MS and severe
      pulmonary hypertension (52 mmHg) who underwent successful percutaneous BMV under
      monitored anaesthesia Care. The anaesthetic considerations in such situations are
      being discussed.

PMID- 29207814
TI  - Congenital Lobar Emphysema: Anaesthetic Challenges and Review of Literature.
AB  - Congenital Lobar Emphysema (CLE) is a developmental anomaly, characterized by
      hyperinflation of one or more pulmonary lobes. It presents in infancy with
      variable degree of respiratory distress due to compression atelectasis. It is
      most often associated with mediastinal shift with subsequent hypoxia. CLE poses a
      diagnostic and therapeutic dilemma. We report a case of five-month-old infant of
      CLE requiring left lobectomy, who was previously being treated for pneumonia
      which was unresponsive to medical therapy. Anaesthetic challenges experienced
      during the case and a brief review of literature is presented.

PMID- 29207815
TI  - Anaesthetic Management in Transoral Endoscopic Thyroidectomy.
AB  - Young females undergoing thyroid surgery are apprehensive about the surgical
      scar. This leads to the introduction of Transoral Endoscopic Thyroidectomy
      (TOET). TOET is gaining popularity for its minimally invasive and cosmetically
      sound approach to perform thyroidectomies in young patients. The surgical site
      being the mouth orifice poses a challenge to the anaesthesiologist to secure a
      definitive airway. The case report is that of a young female undergoing TOET for
      whom we have successfully performed nasal intubation with a North Pole ivory
      endotracheal tube (ET).

PMID- 29207816
TI  - Non-Catheter Related Perioperative Superior Vena Cava Syndrome Following Surgical
      VSD Closure-Role of Transesophageal Echocardiography.
AB  - Unintentional iatrogenic surgical complications can complicate the operative and
      postoperative courses of paediatric cardiac surgery patients. Unless recognized
      and treated early, it's possible, these complications may lead to a prolonged
      hospital stay, increased treatment cost, morbidity, and even death. Ventricular
      Septal Defect (VSD) is the most common congenital heart defect in children,
      occurring in 50% of all children with congenital heart disease and in 20% as an
      isolated lesion. Herein, we discuss the development of Superior Vena Cava (SVC)
      syndrome following surgical repair of VSD in a nine-month-old child. Early
      clinical diagnosis, immediate confirmation with Transthoracic Echocardiography
      (TTE) and surgical re-exploration led to a good outcome in this patient. If,
      however, we could have performed an intraoperative Trans Esophageal
      Echocardiography (TEE), this complication could have been recognized, even before
      shifting from the operating room.

PMID- 29207817
TI  - Immunohistochemical Expression of Cyclo-oxygenase 2 and Liver X Receptor-alpha in
      Acne Vulgaris.
AB  - Introduction: Acne Vulgaris (AV) is a common inflammatory disease of
      pilosebaceous units. Liver X Receptor-alpha (LXR-alpha) is a ligand activated
      transcription factor. It controls transcription of genes involved in lipid and
      fatty acid synthesis. Cyclo-oxygenase 2 (COX2) is a rate limiting enzyme in
      prostaglandin synthesis. It plays important role in inflammation. Aim: To
      evaluate the immunohistochemical expression of LXR-alpha and COX2 in acne
      vulgaris skin biopsies to explore their possible pathogenic role in this disease.
      Materials and Methods: Sixty five subjects were included (45 cases with AV and 20
      age and gender-matched healthy controls). Skin biopsies were taken from lesional
      and perilesional skin of cases and from site-matched areas of control subjects.
      The evaluation of LXR-alpha and COX2 was done using immunohistochemical
      technique. Data were collected, tabulated and statistically analysed using a
      personal computer with "(SPSS) version 11" program. Chi-square test was used to
      study the association between qualitative variables. Mann-Whitney test was used
      for comparison between quantitative variables. Student's t-test was used for
      comparison between two groups having quantitative variables. Spearman's
      coefficient was used to study the correlation between two different variables.
      Differences were considered statistically significant with p<0.05. Results: COX2
      was upregulated in lesional skin compared with peilesional and control skin both
      in epidermis and pilosebaceous units (p<0.001 for all). Higher epidermal COX2%
      was significantly associated with papulopustular acne (p=0.009) and higher acne
      score (p=0.018). Higher pilosebaceous units COX2% was significantly associated
      with papulopustular acne (p=0.04). LXR-alpha was upregulated in lesional skin
      compared with peilesional and control skin both in epidermis and pilosebaceous
      units (p<0.001 for all). Higher LXR-alpha % in epidermis and pilosebaceous units
      was significantly associated with papulopustular acne (p=0.01 for both) and
      higher acne score (p=0.03 for both). Significant positive correlation was
      detected between COX2% and LXR-alpha % in epidermis (p=0.001, r=0.87) and
      pilosebaceous units (p=0.001, r=0.65). Conclusion: Both LXR-alpha and COX-2 play
      a role in the pathogenesis of acne vulgaris through their effects on cellular
      proliferation, inflammation and lipid synthesis. Research for new therapeutic
      modalities based on their inhibition is needed. More understanding of the
      interaction between LXR-alpha, COX2 and acne lesions may lead to effective
      interference, possibly directed toward specific cell types or steps within
      inflammatory pathways.

PMID- 29207818
TI  - Clinical Efficacy and Safety on Combining 20% Trichloroacetic Acid Peel with
      Topical 5% Ascorbic Acid for Melasma.
AB  - Introduction: Trichloroacetic Acid (TCA) is a versatile peeling agent for
      treatment of melasma. However, Post-Inflammatory Hyperpigmentation (PIH) is
      reported to be the most common side-effect associated with TCA peel. Topical
      Ascorbic Acid (AA) due to its effect as antioxidant and tyrosinase inhibitor
      helps to prevent PIH and maintains the response. Aim: To assess the clinical
      efficacy, safety and reduction in Melasma Quality of Life (MELASQOL) on combining
      20% TCA peel with 5% ascorbic acid cream in epidermal melasma. Materials and
      Methods: This study was conducted in the Department of Dermatology, Pt. Bhagwat
      Dayal Sharma University of Health Sciences, Rohtak. This was an open labelled
      prospective randomized study in which 60 patients of epidermal melasma were
      enrolled for 12 weeks. Patients were divided into two groups: Combination group
      received 20% TCA peel every two weeks with once daily 5% ascorbic acid cream and
      Control group received only 20% TCA peel. Melasma Area Severity Index (MASI) was
      used for evaluating clinical improvement of melasma. Improvement in Quality Of
      Life (QoL) was assessed by MELASQOL scale in both groups. Adverse effects were
      evaluated at each visit. All statistical analysis was carried out with SPSS 20th
      version. The difference in change in mean MASI scoring and MELASQOL scores
      between the two groups were analysed using Mann-Whitney test. The side effects
      between the two groups were compared using Chi-square test. Results: The
      combination group demonstrated a statistically significant improvement in MASI,
      percentage decrease in MASI and quality of life as compared to control group
      after treatment. At the baseline there was no statistically significant
      difference in MASI between the two groups (i.e., MASI in combination group and
      control group were 23.55+/-4.61 and 23.613+/-4.088 respectively). However, it was
      statistically significant at the end of therapy (i.e., MASI in combination group
      was 9.50+/-5.31 and in control group was 15.10+/-4.44). When the results were
      analysed in terms of percentage decrease in MASI from baseline, there was
      statistically significant difference in combination group (i.e., 10.87+/-4.11) as
      compared to control group (i.e., 6.3+/-1.97) after 2nd week of therapy. When the
      mean MELASQOL scores were compared between the two groups at the end of therapy
      (i.e., 12 weeks), it was found to be statistically significantly lower in
      combination group (16.60+/-8.03) as compared to control group (25.90+/-8.17).
      Minor adverse effects like post peel erythema, pruritus, burning and stinging
      sensation were observed in some of the patients, which didn't necessitate
      termination of the therapy. Conclusion: Combination of 20% TCA peel with topical
      5% ascorbic acid is a highly effective, safe and promising therapeutic option in
      treatment of melasma which significantly improves the QoL.

PMID- 29207819
TI  - Effect of Rocker Soled Shoe Design on Walking Economy in Females with Pes Planus.
AB  - Introduction: The energy cost is increased during walking in pes planus condition
      whereas, energy cost during walking using rocker bottom shoes is debatable. Aim:
      To determine the walking economy with rocker soled shoes, when compared with bare
      feet walking in females with pes planus over treadmill. Materials and Methods:
      Seventeen collegiate flat footed females aged 18-25 years were recruited in
      accordance with inclusion and exclusion criteria. Subjects were asked to walk
      barefooted and with rocker soled shoes on treadmill for four minutes at a speed
      of 3.8 km/hour. Oxygen consumption (VO2) was measured directly using PowerLab
      8/35 data acquisition system with Lab Chart Pro (AD Instruments, Australia) one
      minute before walking, four minutes during walking and one minute after walking.
      Rating of Perceived Exertion (RPE) was taken after termination of walking.
      Results: VO2 during barefoot walking was significantly lower than rocker soled
      shoe walking during four-five minutes (p<0.001) and during recovery (p=0.04). RPE
      is significantly lower during barefoot walking than rocker soled shoe walking
      (p<0.001) over treadmill. Conclusion: Oxygen consumption and RPE were increased
      during walking with rocker soled shoe design in comparison to bare feet walking
      over treadmill at same speed.

PMID- 29207820
TI  - Relationship Between Trunk Control and Balance in Children with Spastic Cerebral
      Palsy: A Cross-Sectional Study.
AB  - Introduction: Trunk control is impaired in children with Cerebral Palsy (CP) thus
      influencing their functional balance. However, there is a paucity of literature
      determining the relationship between trunk control and balance in children with
      CP. Aim: To find the relationship between trunk control and balance by means of
      Trunk Control Measurement Scale (TCMS) and Paediatric Balance Scale (PBS).
      Materials and Methods: Twenty four children {age range 8-14 years, Gross Motor
      Function Classification System (GMFCS) Level I-III} with spastic CP were
      recruited and evaluated using TCMS and PBS. The results were expressed as summary
      measures median (M) and Inter-Quartile Range (IQR). The correlation of TCMS and
      PBS were done using Spearman's correlation coefficient. A p-value <0.05 was
      considered statistically significant. Results: The children obtained a median
      score of 52 out of 58 on the TCMS and 50 out of 56 on PBS. There was a
      significantly strong correlation with rs=0.77 and p<0.01. A strong correlation
      (p<0.01) was seen between static, dynamic and total components of TCMS and PBS.
      The median scores of TCMS and PBS had a strong correlation for boys with rs=0.74
      and very strong correlation for girls with rs=0.84. Based on the type of spastic
      CP, diplegics had a very strong correlation with rs=0.85. While based on GMFCS
      levels, Level II and Level III had a very strong correlation (For level II
      rs=0.81 and level III rs=0.86) and weak correlation for level I (rs=0.27).
      Conclusion: Based on gender, topography and severity of the motor impairment both
      trunk control and balance are impaired to a different degree in children with CP.
      The findings of this study showed a high positive correlation between trunk
      control and balance in children with spastic CP.

PMID- 29207821
TI  - Hand-Held Dynamometer is a Reliable Tool to Measure Trunk Muscle Strength in
      Chronic Stroke.
AB  - Introduction: Patients with chronic stroke show atypical coordination of trunk
      movement and they find difficulty during bed mobility and transfer skills due to
      weakness of trunk muscles. Routine bedside clinical examination fails to quantify
      the trunk muscle strength in patients with stroke. Handheld dynamometer is widely
      administered to quantify the strength of extremities, but its reliability on
      testing the trunk muscles strength is limited. Aim: This study aimed at examining
      the reliability of hand-held dynamometer to quantify the strength of trunk muscle
      groups in chronic stroke. Materials and Methods: This reliability study was
      conducted in outpatient clinical settings. Patients with chronic stroke aged
      between 30 and 80 years and an ambulatory capacity of 10-meter distance
      volunteered in the study. The strength of trunk flexors, extensors, rotators
      towards most and least affected sides and bilateral lateral flexors was examined
      by break test using hand-held dynamometer and the isometric strength was reported
      in pounds (lb.). These tests were carried out by two physical therapists
      independently at two time points and the assessment procedure was standardized.
      Pearson's correlation test was conducted to observe the reliability of
      dynamometer strength testing i.e., internal consistency of the measure and intra
      class correlation coefficient (r). Results: Of the 85 study participants, 51 of
      them had most trunk involvement on the left side and 34 had it on the right side.
      This study showed an excellent intra-rater (0.88-0.98) and inter-rater (0.84
      0.96) reliability of trunk muscle strength testing using hand-held dynamometer.
      Conclusion: Hand-held dynamometer showed excellent intra and inter tester
      reliability to quantify the trunk muscle strength in patients with chronic
      stroke. So this tool can easily be administered in clinical and rehabilitation
      settings for diagnostic and prognostic purposes.

PMID- 29207822
TI  - Estimation of Correlation between Chronological Age, Skeletal Age and Dental Age
      in Children- A Cross-sectional Study.
AB  - Introduction: In the modern era, identification and determination of age is
      imperative for diversity of reasons that include disputed birth records,
      premature delivery, legal issues and for validation of birth certificate for
      school admissions, adoption, marriage, job and immigration. Several growth
      assessment parameters like bone age, dental age and the combination of both have
      been applied for different population with variable outcomes. It has been well
      documented that the chronological age does not necessarily correlate with the
      maturational status of a child. Hence, efforts were made to determine a child's
      developmental age by using dental age (calcification of teeth) and skeletal age
      (skeletal maturation). Aim: The present study was aimed to correlate the
      chronological age, dental age and skeletal age in children from Southeastern
      region of Andhra Pradesh, India. Materials and Methods: Out of the total 900
      screened children, only 100 subjects between age groups of 6-14 years with a mean
      age of 11.3+/-2.63 for males and 10.77+/-2.24 for females were selected for the
      study. Dental age was calculated by Demirjian method and skeletal age by modified
      Middle Phalanx of left hand third finger (MP3) method. Pearson's and Spearman's
      correlation tests were done to estimate the correlation between chronological,
      dental and skeletal ages among study population. Results: There was a significant
      positive correlation between chronological age, dental age and all stages of MP3
      among males. Similar results were observed in females, except for a non
      significant moderate correlation between chronological age and dental age in the
      H stage of the MP3 region. Conclusion: The results of the present study revealed
      correlation with statistical significance (p<0.05) between chronological, dental
      and skeletal ages among all the subjects (48 males and 52 females) and females
      attained maturity earlier than males in the present study population.

PMID- 29207823
TI  - An In vitro Study to Compare the Effect of Different Types of Tea with
      Chlorhexidine on Streptococcusmutans.
AB  - Introduction: Tea is the second most commonly consumed beverage in the world
      after water. The leaf and bud of the plant Camellia sinensis produces tea. The
      different forms of tea are 'non-fermented' green tea, 'semi-fermented' oolong tea
      and 'fermented' black tea according to the manufacturing process. Streptococcus
      mutans is the main causative organism in dental caries and plaque formation. Aim:
      The present study was undertaken to determine the antibacterial effectiveness of
      aqueous and ethanol extracts of green tea, black tea and oolong tea against S.
      mutans in comparison with 0.2% chlorhexidine. Materials and Methods: An in vitro
      study was conducted to compare the effectiveness of aqueous and ethanol extracts
      of green tea, black tea and oolong tea with 0.2% chlorhexidine against S. mutans.
      Chlorhexidine 0.2% commercially available as mouthwash was used as such for
      comparison. The antimicrobial activity was determined using agar well diffusion
      method. About 50 ul of the aqueous and ethanol extracts of tea and 0.2%
      chlorhexidine were inoculated into the wells prepared on blood agar plates
      smeared with S. mutans. The agar plates were incubated for 24 hours after which
      the diameter of the zone of inhibition was measured. Analysis of Variance (ANOVA)
      followed by Tukey's post hoc test were used for statistical analysis. Results:
      The mean zone of inhibition of the aqueous extracts of green tea, black tea,
      oolong tea and chlorhexidine was found to be 16.33 mm, 10.33 mm, 19.66 mm and 22
      mm respectively. The mean zone of inhibition of the ethanol extracts of green
      tea, black tea, oolong tea and chlorhexidine was found to be 14 mm, 9 mm, 20.66
      mm and 22 mm respectively. The study result state that the inhibitory effect of
      chlorhexidine is almost similar to that of oolong tea followed by green tea and
      black tea. Conclusion: From the present study, it can be concluded that the
      aqueous and ethanol extracts of oolong tea showed highest antimicrobial activity
      compared to green tea and black tea.

PMID- 29207824
TI  - Comparative Evaluation of Antiplaque Efficacy of Coconut Oil Pulling and a
      Placebo, Among Dental College Students: A Randomized Controlled Trial.
AB  - Introduction: Oil pulling, has been extensively used as traditional Indian folk
      remedy since many years to prevent dental diseases and for strengthening teeth
      and gums. Aim: To compare and evaluate antiplaque efficacy of coconut oil pulling
      with a placebo among dental students, in Hyderabad city of India. Materials and
      Methods: A randomized controlled study was carried out among 40 dental students.
      Out of 40, 20 subjects were randomly assigned to study group and other 20 to
      control group. Subjects in the study group were given the coconut oil and control
      group a placebo, and advised to rinse for 10 minutes, once daily in the morning
      for a period of seven days. Plaque levels were assessed on day zero, third and
      seventh day using Turesky-Gilmore-Glickman Modification of the Quigley-Hein
      Plaque Index (1970) for both the groups. Results: The mean plaque scores showed a
      significant difference at baseline, third day and seventh day among both study
      (p<0.001) and control groups (p<0.001). Group wise comparison revealed, though
      the mean plaque scores were low among study group on third day and seventh day on
      comparison with the control group, significant difference was noticed only on the
      seventh day. Furthermore, the mean percentage reduction of plaque scores were
      also significant only on the seventh day with a high mean plaque reduction among
      study groups (p<0.001). Conclusion: Oil pulling is effective in controlling
      plaque levels.

PMID- 29207825
TI  - Global Search Trends of Oral Problems using Google Trends from 2004 to 2016: An
      Exploratory Analysis.
AB  - Introduction: Oral diseases are pandemic cause of morbidity with widespread
      geographic distribution. This technology based era has brought about easy
      knowledge transfer than traditional dependency on information obtained from
      family doctors. Hence, harvesting this system of trends can aid in oral disease
      quantification. Aim: To conduct an exploratory analysis of the changes in
      internet search volumes of oral diseases by using Google Trends(c) (GT(c)).
      Materials and Methods: GT(c) were utilized to provide real world facts based on
      search terms related to categories, interest by region and interest over time.
      Time period chosen was from January 2004 to December 2016. Five different search
      terms were explored and compared based on the highest relative search volumes
      along with comma separated value files to obtain an insight into highest search
      traffic. Results: The search volume measured over the time span noted the term
      "Dental caries" to be the most searched in Japan, "Gingivitis" in Jordan, "Oral
      Cancer" in Taiwan, "No Teeth" in Australia, "HIV symptoms" in Zimbabwe, "Broken
      Teeth" in United Kingdom, "Cleft palate" in Philippines, "Toothache" in Indonesia
      and the comparison of top five searched terms provided the "Gingivitis" with
      highest search volume. Conclusion: The results from the present study offers an
      insight into a competent tool that can analyse and compare oral diseases over
      time. The trend research platform can be used on emerging diseases and their
      drift in geographic population with great acumen. This tool can be utilized in
      forecasting, modulating marketing strategies and planning disability limitation
      techniques.

PMID- 29207826
TI  - The Association between Periodontal Status, Serum Lipid Levels, Lipoprotein
      Associated Phosholipase A2 (Lp-PLA2) in Chronic Periodontitis Subjects and
      Healthy Controls.
AB  - Introduction: Lipoprotein associated phospholipase A2 (Lp-PLA2) has been explored
      as a potential biomarker for Cardiovascular Disease (CVD). The human Lp-PLA2 is a
      serine-dependent, Ca2+- independent enzyme. It gives way to oxidised free fatty
      acids and lysophosphatidyl choline by hydrolysing oxidised phospholipids, that
      leads to smooth muscle cell apoptosis, inflammatory cell chemotaxis and
      endothelial cell dysfunction in CVD. Owing to its role in inflammation, it may
      influence the development and progression of periodontitis as well. Aim: To
      compare the demographic variables, Gingival Index(GI), Bleeding On Probing (BOP),
      Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) with serum lipid
      profile and Lp-PLA2 level in Chronic Periodontitis (CP) subjects. Materials and
      Methods: A total of 75 subjects were selected and divided into three groups;
      based on the inclusion and exclusion criteria: Group I - 25 subjects with severe
      generalized CP with CAL >= 5 mm in more than 30% of sites. Group II -25 subjects
      with moderate generalized CD with clinical CAL 3 mm-4 mm in more than 30% of
      sites. Group III- 25 systemically and periodontally healthy volunteers who served
      as control. Clinical parameters such as Plaque Index (PI), BOP, Probing Depth
      (PD) and CAL, lipid profile such as Total Cholesterol (TC), Triglyceride (TG),
      High density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Very Low Density
      Lipoprotein (VLDL) as well as Lp-PLA2 were assessed. One-way ANOVA and Tukey's
      Post-hoc test were used for data analysis. Results: Age was higher in Group I and
      II when compared to Group III. Group II showed a significant correlation between
      PI and LDL. In Group III, lower PI was significantly correlated with high HDL and
      low LDL and BOP was positively correlated with TG and HDL. A significant
      association of Lp-PLA2 was found to be higher with increase in the TG and VLDL
      level in Group I and Group II when compared to Group III. Conclusion: The study
      concluded that Lp-PLA2, TG and VLDL already being a predictor biomarker for
      atherosclerotic disease can be an inflammatory marker for periodontitis.

PMID- 29207827
TI  - To Evaluate the Correlation Between Skeletal and Dental Parameters to the Amount
      of Crowding in Class II Div. 1 Malocclusions.
AB  - Introduction: Crowding of teeth is one of the most common problem that motivates
      the patient to seek orthodontic treatment. Determination of etiology of crowding
      could have a significant effect on treatment planning and prognosis of Class II
      malocclusion. Aim: Aim of this study was to evaluate the relationship of skeletal
      and dental parameters to amount of dental crowding in patients with Class II
      Divison 1 (div.1) malocclusion. Materials and Methods: Pretreatment lateral
      cephalograms and dental casts of 60 patients with skeletal Class II malocclusion
      were collected for the study. The sample was divided into two groups according to
      severity of pretreatment mandibular crowding. Group I consisted of cases with
      crowding >=3 mm and Group II with crowding <3 mm. Lateral cephalograms for each
      patient was manually traced and skeletal parameters (effective maxillary and
      mandibular length, mandibular plane angle, Y Axis, lower anterior face height)
      and dental parameters (axial inclination of lower incisor, inclination of lower
      incisor to mandibular plane, interincisal angle) were measured. Unpaired t-test
      was used for intergroup comparison and relationship between different
      measurements was investigated using Pearson correlation coefficient. Results:
      Among the skeletal parameters measured, only effective mandibular length
      exhibited statistically significant difference between the two groups. No
      statistically significant difference was found between the two groups for any of
      the dental parameters. Significant inverse correlation was found between
      mandibular crowding and effective mandibular length. Conclusion: Subjects with
      Class II div.1 malocclusion and moderate to severe mandibular crowding have
      significantly smaller effective mandibular base length than subjects with the
      same malocclusion and slight mandibular crowding.

PMID- 29207828
TI  - Micronucleus Assay: An Early Diagnostic Tool to Assess Genotoxic Changes in
      Patients with Tobacco Use, Oral Leukoplakia and Oral Submucous Fibrosis.
AB  - Introduction: Micronuclei (MNi) are acentric chromatid or chromosome fragments
      produced via genetic damage through genotoxic agents contained in tobacco and
      betel nut. Evidently, the various Oral Potentially Malignant Disorders (OPMDs)
      like oral lichen Planus, oral leukoplakia and Oral Submucous Fibrosis (OSMF)
      demonstrate MNi, as a substantiation of genetic damage. As these changes can be
      easily appreciated in oral exfoliated cells, an exfoliated cell based MNi assay
      might be utilized as handy and non invasive biomonitoring tool for gauging the
      genetic damage and hence the propensity for malignant transformation in OPMDs. To
      this end, MNi are definitely easier to evaluate when compared to chromosome
      aberrations. Aim: To compare the MNi frequency in normal mucosa, in individuals
      using various tobacco forms without oral leukoplakia, individuals using various
      tobacco forms with oral leukoplakia, and areca nut chewers with OSMF, using three
      different stains. Materials and Methods: Oral exfoliated cells from 50 cases of
      normal mucosa (Group I), 50 cases of tobacco chewing people without Oral
      Leukoplakia (Group II), 50 cases of people with Oral Leukoplakia (Group III) and
      50 cases of areca nut chewers with OSMF (Group IV) were taken. MNi frequencies
      were compared in these groups using three different stains i.e., Papanicolaou
      (PAP) stain, May Grunwald Giemsa (MGG) stain and Feulgen stain. The data between
      cases (Group II, III and IV) and control groups (Group I) was analyzed by Kruskal
      Wallis Test. The comparison between two independent groups was done by Mann
      Whitney U test and interstain comparison between cases and control was done by
      Wilcoxon Signed Rank Test and the individual p-value was obtained. Results: A
      significant increase in the count was observed during transition of normal mucosa
      to OPMDs. The best stain for detecting MNi was PAP stain followed by MGG stain
      and Feulgen stain. Conclusion: The higher mean MNi count for PAP stain and MGG
      stain could be attributed to nonspecific staining. Further study using a larger
      sample size on quantitative assessment of MNi count in various OPMDs is
      warranted.

PMID- 29207829
TI  - Evaluation of Tumour Associated Macrophages and Angiogenesis in Ameloblastoma.
AB  - Introduction: Ameloblastoma is a locally invasive odontogenic neoplasm that has a
      high recurrence rate. The invasion of adjacent tissue is supported by
      angiogenesis stimulated by Tumour-Associated Macrophages (TAMs). TAMs are
      macrophages modified in the milieu of the tumour microenvironment and have very
      weak or no ability to present antigens. Thus, there is collaboration between the
      tumour and the tumour microenvironment to maintain tumour enlargement. TAMs exist
      as the classically activated M1 macrophages that possess antitumour activity and
      the otherwise activated M2 macrophages that support tumour invasion and
      metastasis. Aim: To investigate the relative expression and topography of TAMs
      and CD34 in ameloblastoma in order to assess their affiliation and effect on
      tumour growth. Materials and Methods: Forty-six Formalin Fixed Paraffin Embedded
      (FFPE) blocks of ameloblastoma were processed for Abcam Mouse monoclonal Anti
      CCR7 antibody, Abcam Rabbit polyclonal Anti-CD206 antibody and Dako Mouse
      monoclonal Anti-CD34 antibody QBEnd-10. Cytoplasmic/membrane brown staining was
      taken as positive for all antibodies. The relative percentage of TAMs was
      classified as: <5%, 5-25%, 25-50% and >50%. TAMs related Microvessel Density
      (MVD) was evaluated as the mean of the three-recorded values. Cases with no CD34+
      vessels adjacent to the TAMs region had MVD score of 0. Simple descriptive
      statistics was applied. Results: Macrophages adjacent to peri-tumour islands were
      marked by CD206 and CCR7 and we noted negligible intra-tumour presence of
      positive macrophages. The percentage of positive CCR7 immune cells was greater
      than that for CD206 in 38 (82.6%) cases, approximately equal to CD206 in 6 (13%)
      cases, and the CD206 expression was more than CCR7 in only 2 (4.3%) cases. In 34
      (73.9%) cases, the area of MVD did not overlap with the region of TAMs but in 4
      (8.7%) cases (where MVD overlapped TAM1), the average MVD score was 20.
      Conclusion: The relative percentage of TAM1 exceeds TAM2 in peri-tumoural areas
      of ameloblastoma, conferring anti-angiogenic and hence anti-tumour activity on
      the tumour.

PMID- 29207830
TI  - Assessment of Pulp Oxygen Saturation Levels by Pulse Oximetry for Pulpal Diseases
      -A Diagnostic Study.
AB  - Introduction: Diagnosis of pulpal inflammation is a key to endodontics. Pulse
      oximetry is a true vitality testing device which relies on oxygen saturation
      levels of pulp and helps in diagnosis of different pulpal conditions. Aim: The
      aim of the study was to analyse oxygen saturation levels of different pulpally
      inflamed teeth by using pulse oximetry. Materials and Methods: Hundred patients
      were included in the study and categorized into five groups based on pulpal
      status of the test tooth by using heat test and cold test. Twenty patients were
      recruited in each of the experimental groups i.e., Reversible Pulpitis (RP),
      Irreversible Pulpitis (IP), Pulpal Necrosis (PN), Positive Control (PC, healthy
      teeth), and Negative Control (NC, endodontically treated teeth). Oxygen
      saturation levels of all the groups were measured along with each patient index
      finger oxygen saturation readings. Results were analysed by using ANOVA and Tukey
      HSD tests. Results: The mean oxygen saturation levels of RP, IP, PN, PC and NC
      were 85.4%, 81.6%, 70.7%, 94.6% and 0 respectively. There was significant
      difference in the oxygen saturation levels between all the groups. Conclusion:
      Pulse oximeter is an effective tool in diagnosing different pulpal pathologies
      especially PN which was interpreted inaccurately by thermal tests.

PMID- 29207831
TI  - Comparison of Gingival Biotype between different Genders based on Measurement of
      Dentopapillary Complex.
AB  - Introduction: Clinical and aesthetic outcomes after periodontal or implant
      surgical procedures are determined by anatomical and morphological
      characteristics of the gingiva like width of keratinized gingiva, thickness of
      gingiva and alveolar bone. Therefore, the knowledge of gingival biotype plays an
      important role in modifying the dental therapeutic procedures for the desired
      outcome and predictability. Aim: The aim of the present study was to assess and
      compare the gingival biotype among genders by clinical, photographic and
      radiographic parameters. Materials and Methods: A total of 800 subjects (400
      males and 400 females) were considered for the study. Width of keratinized
      gingiva (GW), transparency of the periodontal probe through the sulcus (TRAN)
      were assessed clinically; Crown Width/Crown Length ratio (CW/CL) and Papillary
      Height (PH) were assessed photographically; Gingival Thickness (GT1, GT2, GT3)
      and Alveolar bone Thickness (AT1, AT2, AT3) were assessed radiographically. The
      obtained data was correlated to compare the gingival biotype between males and
      females. The collected data was statistically analysed using Pearson correlation
      coefficient (r) with the corresponding 95% confidence interval. Results: The TRAN
      at GT1, GT2 and GT3 as well as at AT1, AT2 and AT3 showed a very strong positive
      correlation in males (r>0.8) as compared to females (r<0.8). A very strong
      positive correlation was observed between GT1, GT2, GT3 and AT1, AT2, AT3 in
      males (r>0.9) as compared to females (r<0.7). Conclusion: There are definite
      differences in the gingival biotype among different genders with predominance of
      a thin gingival biotype with reduced alveolar bone thickness in females as
      compared to males.

PMID- 29207832
TI  - A Comparison of Clinicopathological Differences in Oral Squamous Cell Carcinoma
      in Patients Below and Above 40 Years of Age.
AB  - Introduction: Recent times have revealed an increase in incidence of Oral
      Squamous Cell Carcinoma (OSCC) in young adults including those who lack
      association with typical risk factors such as tobacco. There are reported
      variations in clinical behaviour of tumours in young and older individuals. Aim:
      Present study evaluated differences in clinicopathological characteristics
      between two groups of OSCC, below and above 40 years of age. Materials and
      Methods: An analytical study was performed on two groups of OSCC patients, below
      and above 40 years of age. Clinicopathological parameters of site distribution,
      type of habit, histological grade, nodal metastasis, margin status, mitotic index
      and Argyrophilic Nucleolar Organizing Regions (AgNOR) count were compared. Chi
      square test and Students t- test were applied for statistical analysis. Results:
      Present study revealed that mean AgNOR count was significantly higher in older
      group (6.38) than younger group (4.27). However, no significant differences were
      noted in site distribution, tobacco habit, histological grade, mitotic index,
      nodal metastasis and status of resected surgical margins between the two age
      groups. A trend for increased metastasis and poor histological differentiation
      was also observed in the older and younger age group respectively. Most common
      site was buccal mucosa followed by tongue in both groups. Conclusion: Reasons for
      documented variability in tumour characteristics between young and older patients
      are currently unclear. Difference in AgNOR count found in present study is
      suggestive of variability in proliferative and ploidy characteristics between
      different age groups and supports the hypothesis of genetic and epigenetic
      influences in development of oral cancer.

PMID- 29207833
TI  - Possible Role of Bcl-2 Expression in Metastatic and Non Metastatic Oral Squamous
      Cell Carcinoma.
AB  - Introduction: Oral carcinoma is a global health problem. India accounts for one
      third of world burden with high prevalence rate of 2.5 million and mortality rate
      of 5.5 lacs per year. Oral carcinogenesis is a multistage process that frequently
      involves invasion and metastasis that needs early detection and treatment to
      improve the overall quality of life. The ability of Oral Squamous Cell Carcinoma
      (OSCC) to metastasize to lymph nodes does not always show a relationship with
      clinical staging. A spectrum of molecular mechanisms is involved in
      carcinogenesis, where defect in the regulation of apoptosis is assumed to
      contribute to the pathogenesis and progression of cancer. Apoptosis regulatory
      genes include the antiapoptotic protein such as B-cell lymphoma-2 (Bcl-2) gene
      that might be used as a molecular marker to evaluate the biological behaviour of
      oral cancer. Aim: To evaluate and correlate the Bcl-2 expression in OSCC patients
      with lymphnode metastasis and without metastasis. Materials and Methods: The
      study comprised of 30 samples, 15 cases of metastatic and 15 non-metastatic
      primary OSCC. All the cases were stained for routine Hematoxylin and Eosin (H&E),
      and Bcl-2 antibody by immunohistochemistry. The H&E stained sections were
      evaluated for Lymphocytic Infiltrate (LI) and Pattern Of Invasion (POI). Bcl-2
      stained sections were evaluated for staining intensity and distribution. The
      differences between the groups were statistically analysed using chi-square test.
      Results: The histopathological parameters, LI and POI did not show any
      statistical difference between the study groups. Expression of Bcl-2 in OSCC was
      33.3% among the study groups, where metastatic group showed a positive expression
      of 13.3% and 20% in non-metastatic OSCC that did not show statistically
      significance among the study groups. Conclusion: There was no significant
      difference in the expression of Bcl-2 between the study groups. Apoptosis is
      regulated by interaction among the Bcl-2 gene family. Hence, evaluation of Bcl-2
      along with other apoptotic regulating proteins could define the role in
      pathogenesis and prognosis of metastatic and non-metastatic OSCC.

PMID- 29207834
TI  - Clinical Evaluation of Quality of Obturation and Instrumentation Time using Two
      Modified Rotary File Systems with Manual Instrumentation in Primary Teeth.
AB  - Introduction: Pulp therapy in primary teeth has been performed using various
      instrumentation techniques. However, the conventional instrumentation technique
      used for root canal preparation in primary teeth is hand instrumentation. Various
      Nickel-Titanium (Ni-Ti) instruments are available to perform efficient root canal
      preparation in primary teeth. These Ni-Ti instruments has been designed to aid in
      better root canal preparation in permanent teeth but are rarely used in primary
      teeth. It is necessary to assess the feasibility of using these adult rotary
      files with a modified sequence in primary teeth. Aim: To compare the quality of
      obturation and instrumentation time during root canal preparation using hand
      files and modified rotary file systems in primary molars. Materials and Methods:
      Forty-five primary mandibular molars were randomly assigned to three experimental
      groups (n=15). Group I was instrumented using k-hand files, Group II with S2
      ProTaper universal file and Group III with 0.25 tip 4% taper K3 rotary file.
      Standardized digital radiographs were taken before and after root canal
      instrumentation. Root canal preparation time was also recorded. Statistical
      analysis of the obtained data was done using SPSS Software version 17.0. An
      intergroup comparison of the instrumentation time and the quality of obturation
      was done using ANOVA and Chi-square test with the level of significance set at
      0.05. Results: No significant differences were noted with regard to the quality
      of obturation (p=0.791). However, a statistically significant difference was
      noted in the instrumentation time between the three groups (p<0.05). ProTaper
      rotary system had significantly lesser instrumentation time when compared to that
      of K3 rotary system and hand file system. Conclusion: The hand files, S2 ProTaper
      Universal and K3 0.25 tip 4% taper files systems performed similarly with respect
      to the quality of obturation. There was a significant difference in
      instrumentation time with manual instrumentation compared to the modified rotary
      file systems in primary teeth.

PMID- 29207835
TI  - SEM Evaluation of Enamel Surface Changes and Enamel Microhardness around
      Orthodontic Brackets after Application of CO2 Laser, Er,Cr:YSGG Laser and
      Fluoride Varnish: An In vivo Study.
AB  - Introduction: One of the most undesirable consequences of orthodontic treatment
      is occurrence of enamel demineralization around orthodontic brackets. Numerous in
      vitro studies have reported the prevention of enamel demineralization by surface
      treatment with lasers and fluoride varnish. Aim: To evaluate the changes on the
      enamel surface and microhardness around orthodontic brackets after surface
      treatment by CO2 laser, Er, Cr:YSGG laser and fluoride varnish in vivo. Materials
      and Methods: A double blind interventional study was carried out on 100 premolars
      which were equally divided into five groups, out of which one was the control
      group (Group 0). The intervention groups (Group I to IV) comprised of patients
      requiring fixed orthodontic treatment with all 4 first premolars extraction.
      Brackets were bonded on all 80 premolars which were to be extracted. Enamel
      surface treatment of Groups I, II and III was done by CO2 laser, Er, Cr:YSGG
      laser and 5% sodium fluoride varnish respectively and Group IV did not receive
      any surface treatment. A modified T-loop was ligated to the bracket and after two
      months, the premolars were extracted. Surface changes were evaluated by Scanning
      Electron Microscopic (SEM) and microhardness testing. Comparison of mean
      microhardness between all the groups was assessed using post-hoc test with
      Bonferroni correction. Results: Group I showed a melted enamel appearance with
      fine cracks and fissures while Group II showed a glossy, homogenous enamel
      surface with well coalesced enamel rods. Group III showed slight areas of
      erosions and Group IV presented areas of stripped enamel. Significant difference
      was observed between the mean microhardness (VHN) of Group I, Group II, Group
      III, Group IV and Group 0 with p<0.001. A significant difference of p<0.001 was
      observed while comparing Group I vs II,III,IV,0 and Group II vs III,IV,0.
      However, difference while comparing Group III vs IV was p=0.005 and difference
      between the mean microhardness of Group 0 vs Group III was non significant.
      Conclusion: Surface treatment with Er,Cr:YSGG laser causes a positive alteration
      of the enamel surface increasing its ability to resist demineralization with
      optimum microhardness as compared to CO2 laser and sodium fluoride varnish.

PMID- 29207836
TI  - Recurrent Aphthous Stomatitis: An Assessment of Antioxidant Levels in Plasma and
      Saliva.
AB  - Introduction: Recurrent Aphthous Stomatitis (RAS) is a common oral mucosal
      disorder that affects 20% of the population worldwide. Factors such as trauma,
      stress, genetic, hypersensitivity, nutrition, immune disturbance and hormonal
      imbalance may disturb the oxidant and antioxidant balance of an organism and
      precipitate RAS, but the relationships are poorly understood. Aim: The purpose of
      this study was to evaluate the antioxidant status in plasma and saliva of
      patients with RAS. Materials and Methods: Forty patients with RAS and forty
      healthy individuals were included in the study. The levels of antioxidants such
      as Superoxide Dismutase (SOD), Glutathione Peroxidase (GSHPx) Catalase (CAT) and
      Uric Acid (UA) were measured in plasma and saliva. Statistical analysis was
      performed to compare the two groups using independent t-test and ANOVA. Results:
      Decreased SOD levels were observed in plasma amongst RAS patients (p < 0.03)
      whereas, increased levels were observed in their saliva (p < 0.001) compared to
      the control group. A significant difference (p < 0.001) was noticed in GSHPx
      levels: RAS patients exhibited higher levels in plasma but decreased in saliva
      compared to the control group. CAT activities and UA levels in saliva (p = 0.015
      and p < 0.001 respectively) were observed to be significantly higher in RAS
      patients. Within the RAS group elevated plasma SOD level (p < 0.006) was found in
      patients with major ulcers whereas, an increased plasma UA (p < 0.01) level was
      observed in patients with minor ulcers. Conclusion: The non-equilibrium
      antioxidant levels observed in both plasma and saliva indicate the antioxidant
      status of the body is disturbed in patients with RAS.

PMID- 29207837
TI  - Fracture Resistance of Endodontically Treated Teeth Restored with Biodentine,
      Resin Modified GIC and Hybrid Composite Resin as a Core Material.
AB  - Introduction: The restoration of a severely damaged tooth usually needs a post
      and core as a part of treatment procedure to provide a corono - radicular
      stabilization. Biodentine is a class of dental material which possess high
      mechanical properties with excellent biocompatibility and bioactive behaviour.
      The sealing ability coupled with optimum physical properties could make
      Biodentine an excellent option as a core material. Aim: The aim of the study was
      to determine the fracture resistance of Biodentine as a core material in
      comparison with resin modified glass ionomer and composite resin. Materials and
      Methods: Freshly extracted 30 human permanent maxillary central incisors were
      selected. After endodontic treatment followed by post space preparation and
      luting of Glass fibre post (Reforpost, Angelus), the samples were divided in to
      three groups based on the type of core material. The core build-up used in Group
      I was Biodentine (Septodont, France), Group II was Resin-Modified Glass Ionomer
      Cement (GC, Japan) and Group III was Hybrid Composite Resin (TeEconom plus,
      Ivoclar vivadent). The specimens were subjected to fracture toughness using
      Universal testing machine (1474, Zwick/Roell, Germany) and results were compared
      using One-way analysis of variance with Tukey's Post hoc test. Results: The
      results showed that there was significant difference between groups in terms of
      fracture load. Also, composite resin exhibited highest mean fracture load (1039.9
      N), whereas teeth restored with Biodentine demonstrated the lowest mean fracture
      load (176.66 N). Resin modified glass ionomer exhibited intermediate fracture
      load (612.07 N). The primary mode of failure in Group I and Group II was
      favourable (100%) while unfavourable fracture was seen in Group III (30%).
      Conclusion: Biodentine, does not satisfy the requirements to be used as an ideal
      core material. The uses of RMGIC's as a core build-up material should be limited
      to non-stress bearing areas. Composite resin is still the best core build-up
      material owing to its high fracture resistance and bonding to tooth.

PMID- 29207838
TI  - In vitro Evaluation of Resin Infiltrant Penetration into White Spot Lesions of
      Deciduous Molars.
AB  - Introduction: Caries Infiltration is a recent microinvasive restorative technique
      that permits treatment of non-cavitated demineralized lesions, known as White
      Spot Lesions (WSL). Aim: To evaluate the extent of penetration of a commercially
      available resin caries-infiltrant into natural WSL occurring in deciduous tooth
      enamel. Materials and Methods: Deciduous molars with natural WSL on any smooth
      surface were selected and sectioned into halves to yield equal control and
      experimental groups. Therefore, 25 samples in the control group were untreated
      whereas 25 samples in the experimental group were treated with caries-infiltrant
      according to the manufacturer's instructions. Samples were then evaluated under
      cross-polarized light microscope. Lesion Depth (LD) and Penetration Depth (PD) of
      the caries-infiltrant were measured quantitatively and descriptive statistics
      were calculated. Results: Mean LD (standard deviation) for all samples (n=50) was
      367(+/-182) MUm. Caries-infiltrant demonstrated varying depths of resin
      penetration into the natural white spot lesions of deciduous molars. Mean PD
      (standard deviation) was 352 (+/- 141) MUm. Conclusion: Resin-infiltrants can
      deeply and predictably penetrate enamel porosities in natural WSL in deciduous
      molars and impede lesion progression and prevent cavitation.

PMID- 29207839
TI  - Evaluation of Effect of Irrigants with or without Surfactant on Root Canal
      Transportation by Cone Beam Computed Tomography-An In vitro Study.
AB  - Introduction: Maintenance of original canal anatomy with proper disinfection is
      our primary goal to achieve during root canal instrumentation. Surfactants are
      added to irrigating solution to promote deeper penetration into dentinal tubules.
      Aim: The aim of this study was to evaluate the influence of addition of
      surfactants to Sodium Hypochlorite (NaOCl) and Ethylenediaminetetraacetic Acid
      (EDTA) on transportation of root canal. Materials and Methods: Fifty human
      mandibular molars with mesial root curvatures of 10 degrees  - 40 degrees  were
      selected and embedded in silicone impression material to simulate mandibular arch
      form to facilitate imaging process and maintain reproducibility of images. Before
      instrumentation, root canals were scanned by using Cone Beam Computed Tomography
      (CBCT) imaging (Carestream, India). The canals were then prepared with the
      ProTaper Next (PTN) system (Dentsply Maillefer, Ballaigues, Switzerland), using
      one of the following irrigation regimens during the instrumentation and were
      divided into five groups based on irrigation regimens followed: G1 (n=10)
      irrigation with saline solution(control); G2 (n=10)-irrigation with 2.5% NaOCl;
      G3 (n=10)-irrigation with 2.5% NaOCl added with surfactant; G4 (n=10)-irrigation
      with 17% EDTA; G5 (n=10)-irrigation with 17% EDTA added with surfactant. Post
      instrumentation scans were obtained with similar parameters and position as pre
      instrumentation scans by CBCT imaging. Transportation of the root canals were
      then analysed at three cross-sectional planes of pre-instrumentation and post
      instrumentation images at 2 mm, 5 mm, 8 mm from the apical end of the root. The
      data was statistically analyzed using Analysis of Variance (ANOVA) and Tukey post
      hoc test (p<0.05). Results: The mean transportation values were higher in G5.
      Transportation in G3 and G5 was not significantly different compared to G2 and G4
      respectively (p<0.05). Conclusion: Instrumentation using irrigating solutions
      added with surfactant like 1% cetrimide maintained the canal curvature well.

PMID- 29207841
TI  - Effect of Mobile Phone Usage on Nickel Ions Release and pH of Saliva in Patients
      Undergoing Fixed Orthodontic Treatment.
AB  - Introduction: Hand held mobile phones are presently the most popular means of
      communication worldwide and have transformed our lives in many aspects. The
      widespread use of such devices have resulted in growing concerns regarding
      harmful effects of radiations emitted by them. This study was designed to
      evaluate the effects of mobile phone usage on nickel ion release as well as pH of
      saliva in patients with fixed orthodontic appliances. Aim: To assess the level of
      nickel ions in saliva and pH of saliva in mobile phone users undergoing fixed
      orthodontic treatment using inductively coupled plasma atomic emission
      spectrometry. Materials and Methods: A total of 42 healthy patients with fixed
      orthodontic appliance in mouth for a duration of six to nine months were selected
      for the study. They were divided into experimental group (n=21) consisting of
      mobile phone users and control group (n=21) of non mobile phone users. Saliva
      samples were collected from both the groups and nickel ion levels were measured
      using inductively coupled plasma-mass spectroscopy. The pH values were also
      assessed for both groups using pH meter. Unpaired t-test was used for the data
      analysis. Results: Statistical analysis revealed that though the pH levels were
      reduced and the nickel ion levels were higher in the experimental group compared
      to the control group, the results were non significant. Conclusion: Mobile phone
      usage may affect the pH of saliva and result in increased release of nickel ions
      in saliva of patients with fixed orthodontic appliances in the oral cavity.

PMID- 29207840
TI  - Evaluation of the Efficacy of G32 (Commercially Available Ayurvedic Preparation)
      in Reducing Halitosis - A Randomized Controlled Trial.
AB  - Introduction: Oral malodour is a social malady affecting people of all the age
      groups. Effective management of oral malodour is the key to improve the quality
      of life of such people. Aim: To evaluate the effectiveness of ayurvedic
      medication, G32 in controlling oral malodour and comparing the effects with
      Chlorhexidine (CHX). Materials and Methods: This was a single blind randomized
      controlled trial with parallel study design conducted at a hospital in the city
      of Udupi in Southern India. A total of 40 patients suffering with oral malodour,
      aged 17-35 years, were included in this trial. After inclusion into the study,
      the subjects were examined twice, with a one-week interval between both
      examinations. Volatile Sulphur Compounds (VSCs), gingival, plaque and tongue
      coating scores were assessed at both examinations. Subjects were randomly
      allocated to G32 group - ayurvedic formulation (intervention group) and CHX group
      (control group), and were provided with the respective formulations enough to be
      used twice daily for a period of one week. The difference between the mean scores
      of VSCs, plaque, and gingivitis and tongue coating were compared within the
      intervention and control groups, respectively, using paired t-test. Results: Both
      test and control groups showed a significant reduction in VSCs, plaque and
      gingivitis levels. The percentage reductions in VSCs, plaque and gingivitis were
      found to be similar among the two groups. There was no significant difference
      between the preintervention and postintervention scores in both the groups.
      Conclusion: G32, an ayurvedic medication, can be an effective tool to deal with
      oral malodour.

PMID- 29207842
TI  - A Three Month Comparative Evaluation of the Effect of Different Surface Treatment
      Agents on the Surface Integrity and Softness of Acrylic based Soft Liner: An In
      vivo Study.
AB  - Introduction: Acrylic based soft liners are cost effective, yet are inferior in
      durability as compared to silicone based liners. Hence, this study was conducted
      to evaluate if the softness and surface integrity of acrylic based soft liner can
      be maintained by using different surface treatment agents. Aim: To comparatively
      evaluate the effects of Varnish, Monopoly and Kregard surface treatment agents on
      the surface integrity and softness of acrylic based soft liner at baseline, at
      one month and after three months. Materials and Methods: A total of 37
      participants who required conventional maxillary dentures were selected according
      to the determined inclusion and exclusion criteria of the study. In the maxillary
      denture on the denture bearing surface, eight palatal recesses (5 mm x 3 mm) were
      made and filled with acrylic based soft liner (Permasoft). The soft liners in
      these recesses were given surface treatment and divided as control (uncoated),
      Varnish, Monopoly and Kregard groups. The hardness and surface integrity were
      evaluated with Shore A Durometer and Scanning Electron Microscope (SEM)
      respectively at baseline, one month and three months interval. Surface integrity
      between groups was compared using Kruskal-Wallis test. Intergroup comparison for
      hardness was done using ANOVA and Tukey's HSD post-hoc tests. Results: Amongst
      all the groups tested, surface integrity was maintained in the Kregard group, as
      compared to control, Varnish and Monopoly groups for all three time intervals (p<
      0.001). Kregard treated samples also demonstrated significantly higher softness
      at all the time intervals (p<0.001). Conclusion: Surface treatment with Kregard
      demonstrated better surface integrity and softness at all the time intervals.

PMID- 29207843
TI  - Biosynthesis, Characterization and Antibacterial Efficacy of Silver Nanoparticles
      Derived from Endophytic Fungi against P. gingivalis.
AB  - Introduction: Microbial resistance to existing antimicrobial agents in
      periodontal therapy is a growing problem. Therefore, there is a need for
      development of new antimicrobial agents. Aim: To biosynthesize and characterize
      Silver Nanoparticles (AgNPs) using endophytic fungi and to evaluate the
      antibacterial efficacy against P. gingivalis. Materials and Methods: Cut leaf
      segments of Withania Somnifera (Ashwagandha) were used to isolate the fungi.
      Fresh cultures of fungi were inoculated in Erlenmeyer flask of 100 ml Malt
      Glucose Yeast Peptone (MGYP) broth and incubated at 29 degrees C for 72 hours for
      the biomass to grow. Biomass was filtered and cell free fungal filtrate was used
      further. Biosynthesized AgNPs were characterized by visual observation,
      Ultraviolet-Visible (UV-Vis) spectrophotometer, Transmission Electron Microscopy
      (TEM), Selected Area Electron Diffraction Analysis (SAED) and Fourier Transform
      Infrared Spectroscopy (FTIR). Antibacterial efficacy was evaluated by agar
      diffusion method measuring the zone of inhibition. The study groups included
      different concentrations of AgNPs: A (20 MUl), B (40 MUl), C (60 MUl), D (80 MUl)
      and E (100 MUl) of AgNPs, F (0.2% CHX), G (2% CHX), H (Ampicillin) and I (sterile
      distilled water). The data collected for inhibition zones were statistically
      analysed using One-way Anova followed by Tukey post-hoc multiple comparison
      tests. Results: The fungi were identified as Fusarium semitectum.
      Characterization studies showed the colour change from colourless to reddish
      brown; U-V spectrum showed peak 420 nm, TEM revealed the particles spherical in
      shape and 10-20 nm in size. FTIR analysis revealed the presence of functional
      groups. AgNPs 80 MUl and 100 MUl showed mean zone of inhibition 17.33 and 18 mm
      against P. gingivalis. CHX (0.2%) 17.85 and CHX (2%) 19.97 mm, Ampicillin 20.5 mm
      and no zone for sterile distilled water. Conclusion: Biosynthesized AgNPs showed
      efficient antibacterial efficacy against P. gingivalis hence, creates a new
      horizon in periodontal therapy.

PMID- 29207844
TI  - Impact of Nano Hydroxyapatite, Nano Silver Fluoride and Sodium Fluoride Varnish
      on Primary Teeth Enamel Remineralization: An In Vitro Study.
AB  - Introduction: Dental caries is still prevailing worldwide, although different
      anti caries products have been introduced. Each remineralizing agent has its own
      shortcomings. Therefore, looking for new agents to have benefits of previous ones
      with lesser side effects is worthwhile. Aim: To determine the remineralization
      ability of NaF varnish, nano-Hydroxyapatite Serum (n-HAP) and Nano Silver
      Fluoride (NSF) on enamel of primary anterior teeth. Materials and Methods:
      Incipient caries were induced in primary sound anterior teeth by storing each
      specimen in demineralization solution for 72 hours. Then they were randomly
      divided into four groups of 15 samples each: (1) NaF varnish; (2) n-HAP repairing
      serum; (3) NSF and (4) no treatment (control). Surface Microhardness (SMH) was
      assessed with Vickers micro hardness tester before and after demineralization and
      after 10 days of pH-cycling. A total of 12 random specimens from groups 1 to 4 (3
      random samples of each group) were examined by Atomic Force Microscopy (AFM). The
      SMH values were analysed with one-way and repeated measures ANOVA. Level of
      significance was set at p=0.05. Results: Post lesion SMH values significantly
      decreased in all groups (p<0.001). Post treatment SMH values significantly
      increased in comparison to post lesion ones (p<0.001) except for control group
      which was not different statistically (p=0.86). The highest SMH values were
      observed in NSF group (mean 222.90 +/- 28.79). Statistically significant
      differences were shown between all groups (p<0.05). However, NaF varnish and n
      HAP groups were not statistically different (p=0.165). AFM images demonstrated
      protective layers in all treated groups. Conclusion: The results of this in vitro
      study suggest that NSF could have the greatest remineralization efficacy. NaF
      varnish and n-HAP serum were similar in remineralizing initial caries. Future
      clinical studies are recommended for selection of the most appropriate
      remineralizing agent in primary teeth.

PMID- 29207845
TI  - Two Episodes of Trigeminocardiac Reflex During a Pan facial Fracture Surgery, a
      Rare Phenomenon - Case Report and Review of Literature.
AB  - Trigeminocardiac reflex is a sudden physiologic response due to mechanical
      manipulation of any of the branches of trigeminal nerve. Trigeminocardiac reflex
      occurs due to pressure effect or stretching of trigeminal nerve which causes fall
      in blood pressure and decrease in heart rate. In this reflex arc, the trigeminal
      nerve serves as afferent pathway and vagus nerve, which is cardio inhibitory in
      nature, serves as efferent pathway. Two episodes of trigeminocardiac reflex
      during maxillofacial trauma surgery is not a common phenomenon. The present case
      report describes a case of 40-year-old male patient, diagnosed with pan facial
      fracture in which two episodes of trigeminocardiac reflex were seen
      intraoperatively during fracture reduction and fixation of left
      zygomaticomaxillary complex fracture and inferior orbital rim fracture.
      Intraoperative management of trigeminocardiac reflex was done by withholding the
      stimulus and administration of atropine.

PMID- 29207846
TI  - Tiny Creature in Oral Cavity: A Case Report.
AB  - Oral cavity is nidus of much pathology. Some may arise due to altered eating
      habits such as meat, uncooked food etc. The parasitic infections arising from
      ingesting uncooked pork (larva of pork tapeworm) called as cysticercosis and
      being undiagnosed lead to "diagnostic dilemma". Herein we report a case of
      cysticercosis involving the right dorsum of tongue along with review of
      literature.

PMID- 29207847
TI  - Categorization and Management of Various Types of C-Shaped Canals: Two Case
      Reports.
AB  - This case report presents the categorization and management of two cases of C
      shaped canals in need of root canal treatment, based on the available
      classification systems. The prediction of C-shaped root canal morphology using
      radiography and clinical picture is possible through the application of the
      classification schemes proposed in literature. A modified cold lateral compaction
      technique is described for obturation of C-shaped canals partly united by a
      narrow isthmus.

PMID- 29207848
TI  - Bite Force Recording Devices - A Review.
AB  - In dental research, bite force serves as a valuable parameter to evaluate the
      efficacy of masticatory system. A variety of devices with different design and
      working principle have been used to record bite force, but no single device is
      capable to record all the required forces. One may find it difficult to choose a
      device that will fulfil the purpose of recording bite force for research. So, the
      present review aims to report and compare the wide range of devices and will help
      in describing their uses for recording bite force.

PMID- 29207849
TI  - Management of Paediatric Oral Ranula: A Systematic Review.
AB  - Introduction: Ranula is mucous extravasation cyst that occurs in the floor of the
      mouth. There are various methods of management of paediatric oral ranula each of
      which has their own advantage and disadvantage. Aim: The aim of this paper was to
      systematically review the available literature on the management of paediatric
      oral ranula. Materials and Methods: A total of 64 articles were retrieved by
      electronic search. Based on the preset inclusion and exclusion criteria, a total
      of 21 articles were retrieved for full text analysis. The following
      characteristics were assessed from the retrieved articles: author, year of
      publication, study design, sample size, intervention, adverse effects and follow
      up period. Results: The included studies consisted of the following study design:
      Seven articles were prospective clinical study, four articles were retrospective
      review, five articles were case series and five articles were case report. The
      mode of care varied from surgical excision to drug administration and lasers.
      Conclusion: The data obtained from the review, display a lack of high quality
      study, with proper sample size and adequate follow up period. Further, randomized
      clinical trials are required to help the clinicians devise a best treatment
      approach for the management of paediatric oral ranula.

PMID- 29207850
TI  - A Novel Technique of Fabricating a Modified Removable Provisional Prosthesis over
      an Autologous Bone Grafted Maxillary Anterior Edentulous Segment Prior to Implant
      Placement.
AB  - Implant dentistry has provided a lot of surgical as well as prosthetic techniques
      for improving the success of the implants. The surgical technique commonly
      followed now prior to implant placement is bone grafting procedure. One of the
      commonest techniques is the use of autologous block graft harvested from
      mandibular chin region. However, interference in healing as well as excessive
      bone resorption due to the use of removable provisional prosthesis over the bone
      grafted region has been commonly observed/reported. Hence now-a-days, fixed
      provisional prosthesis is preferred over removable provisional prosthesis for the
      added advantages of superior aesthetics and patient acceptance. This article
      highlights a new technique of fabricating removable provisional prosthesis, which
      is superior in aesthetics and strength, consumes less chair time and exerts zero
      pressure onto the grafted site.

PMID- 29207851
TI  - Correspondence: Correlation of Salivary pH, Incidence of Dental Caries and
      Periodontal Status in Diabetes Mellitus Patients: A Cross-Sectional Study.

PMID- 29207852
TI  - The efficacy and safety of high-intensity focused ultrasound ablation of benign
      thyroid nodules.
AB  - High-intensity focused ultrasound (HIFU) is a promising form of thermal ablation
      of benign thyroid nodules, but evidence supporting its use is scarce. The present
      review evaluated the efficacy and safety of single-session HIFU treatment of
      benign thyroid nodules. As reported in the literature, the extent of nodule
      shrinkage following treatment ranged from 48.8% to 68.8%. Like other forms of
      ablation, the shrinkage rate was greatest in the first 3-6 months, and the best
      responders were patients with small (<=10 mL) nodules. Complications were
      uncommon, but temporary vocal cord palsy occurred in 3%-4% of patients, and was
      related to the distance between the HIFU beam and the recurrent laryngeal nerve.
      Despite being safe and efficacious, a larger-scale prospective trial is required.

PMID- 29207853
TI  - Complications Following Transradial Cerebral Angiography : An Ultrasound Follow
      Up Study.
AB  - Objective: The feasibility and usefulness of transradial catheterization for
      coronary and neuro-intervention are well known. However, the anatomical change in
      the catheterized radial artery (RA) is not well understood. Herein, we present
      the results of ultrasonographic observation of the RA after routine transradial
      cerebral angiography (TRCA). Methods: Patients who underwent routine TRCA with
      pre- and post-procedure Doppler ultrasonography (DUS) of the catheterized RA were
      enrolled. We then recorded and retrospectively reviewed the diameter and any
      complicated features of the RA observed on DUS, and the factors associated with
      the diameter and complications were analyzed. Results: A total of 223 TRCAs
      across 181 patients were enrolled in the current study. The mean RA diameter was
      2.48 mm and was positively correlated with male gender (p<0.001) and hypertension
      (p<0.002). The median change in diameter after TRCA was less than 0.1 mm (range, 
      1.3 to 1.2 mm) and 90% of changes were between -0.8 and +0.7 mm. Across 228
      procedures, there were 12 cases (5.3%) of intimal hyperplasia and 22 cases (9.6%)
      of asymptomatic local vascular complications found on DUS. Patients with abnormal
      findings on the first procedure had a smaller pre-procedural RA diameter than
      that of patients without findings (2.26 vs. 2.53 mm, p=0.0028). There was no
      significant difference in the incidence of abnormal findings for the first versus
      subsequent procedures (p=0.68). Conclusion: DUS identified the pre- and post
      procedural diameter and local complications of RA. Routine TRCA seems to be
      acceptable with regard to identifying local complications and changes in RA
      diameter.

PMID- 29207855
TI  - Including the Sheath Rinse to Improve Cellular Yield in Biliary Brushing
      Cytology.

PMID- 29207854
TI  - Recent Development of Techniques and Devices in Colorectal Endoscopic Submucosal
      Dissection.
AB  - Colorectal endoscopic submucosal dissection (ESD) is now a well-established
      endoscopic treatment for early-stage colorectal neoplasms, especially in Asian
      countries, including Japan. Despite the spread of colorectal ESD, there are still
      situations in which achieving successful submucosal dissection is difficult.
      Various novel techniques and devices have been developed to overcome these
      difficulties, and past reports have shown that some of these strategies can be
      applied to colorectal ESD. We review several recent developments in the field.
      The techniques reviewed include the pocket creation method and traction methods
      and the devices reviewed include the overtube with balloon and electrosurgical
      knives with water-jet function. These improved techniques and devices can
      facilitate safer, more reliable ESDs and expand its applicability and
      acceptability all over the world.

PMID- 29207856
TI  - Diagnosis of Pancreatic Neuroendocrine Tumors.
AB  - Pancreatic neuroendocrine tumors (PNETs) are relatively rare; however, the
      incidence has increased over the last few decades. They are classified as
      functional or non-functional tumors according to the presence of associated
      clinical symptoms. The majority are non-functional tumors. For classification and
      staging, the World Health Organization 2010 classification system is the most
      commonly accepted. Chromogranin A is the most sensitive marker but has
      insufficient specificity. In general, PNETs are hypervascular tumors, and
      multiphasic contrast-enhanced computed tomography is considered the first choice
      for imaging study. Multiphasic magnetic resonance imaging can detect PNETs
      smaller than 2 cm and small liver metastasis compared with other modalities.
      Somatostatin receptor scintigraphy is often used in cases where functional PNETs
      are suspected. Positron emission tomography (PET) scan with 18F
      fluorodeoxyglucose cannot visualize PNETs, but PET with 68-Ga DOTATATE can.
      Endoscopic ultrasonography can characterize smaller PNETs using contrast and
      confirm histology through fine needle aspiration or biopsy. In this article, we
      review the characteristics of grading systems and diagnostic modalities commonly
      used for PNETs.

PMID- 29207857
TI  - Diagnosis and Management of Rectal Neuroendocrine Tumors.
AB  - The incidence of rectal neuroendocrine tumors (NETs) has increased by almost ten
      fold over the past 30 years. There has been a heightened awareness of the
      malignant potential of rectal NETs. Fortunately, many rectal NETs are discovered
      at earlier stages due to colon cancer screening programs. Endoscopic ultrasound
      is useful in assessing both residual tumor burden after retrospective diagnosis
      and tumor characteristics to help guide subsequent management. Current guidelines
      suggest endoscopic resection of rectal NETs <=10 mm as a safe therapeutic option
      given their low risk of metastasis. Although a number of endoscopic interventions
      exist, the best technique for resection has not been identified. Endoscopic
      submucosal dissection (ESD) has high complete and en-bloc resection rates, but
      also an increased risk of complications including perforation. In addition, ESD
      is only performed at tertiary centers by experienced advanced endoscopists.
      Endoscopic mucosal resection has been shown to have variable complete resection
      rates, but modifications to the technique such as the addition of band ligation
      have improved outcomes. Prospective studies are needed to further compare the
      available endoscopic interventions, and to elucidate the most appropriate course
      of management of rectal NETs.

PMID- 29207858
TI  - Can Endoscopic Ultrasonography Prevent Unnecessary Endoscopic Retrograde
      Cholangiopancreatography in Patients with High and Intermediate Likelihood of
      Choledocholithiasis?

PMID- 29207859
TI  - Clinical Significance of Risk Factors for Asymptomatic Peptic Ulcer Disease.

PMID- 29207860
TI  - Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including
      Ethanol and Radiofrequency Ablation.
AB  - Pancreatic neuroendocrine tumors (PNETs) are increasingly being detected, though
      usually as incidental findings. Majority of the PNETs are non-functional and
      surgical resection is the standard of care for most of them. However, in patients
      with small PNETs localized within the pancreas, who are unfit or unwilling for
      surgery, alternate methods of treatment are needed. Direct methods of ablation of
      PNETs, using either ethanol injection or radiofrequency ablation (RFA), are
      emerging as effective methods. The limited literature available as case reports
      or case series on endoscopic ultrasound (EUS)-guided local ablation using either
      ethanol or RFA has demonstrated safety and efficacy along with short- to medium
      term sustained relief. Long-term benefits with these local ablative therapies are
      awaited. Comparative studies are needed to show which of these two competing
      technologies is superior. Finally, comparative trials of EUS-guided ablation with
      surgical resection in terms of efficacy and safety will ensure their place in the
      management algorithm.

PMID- 29207861
TI  - Endoscopic Resection of Early Gastric Cancer with Undifferentiated-Type
      Histology.

PMID- 29207863
TI  - Proper Treatment Option for Small Rectal Neuroendocrine Tumors Using Precut
      Endoscopic Mucosal Resection.

PMID- 29207862
TI  - Diagnosis and Management of Upper Gastrointestinal Neuroendocrine Tumors.
AB  - Upper gastrointestinal neuroendocrine tumors (NETs) are rare tumors which are
      increasingly recognised by practising endoscopists. After confirmation by
      endoscopic biopsies of these focal lesions, many questions may arise. As NETs are
      less frequently encountered compared to other malignancies or gastrointestinal
      pathology, many endoscopists may not fully understand the natural history,
      diagnosis and management of these tumors. In this review, we aim to update the
      practising endoscopist on the key clinical features and management of patients
      with upper gastrointestinal NET.

PMID- 29207864
TI  - Long-term cosmesis following a novel schedule of accelerated partial breast
      radiation in selected early stage breast cancer: result of a prospective clinical
      trial.
AB  - PURPOSE: There is controversy regarding the cosmetic outcome after accelerated
      partial breast radiation (APBR). We report the cosmetic outcome from a single-arm
      prospective clinical trial of APBR delivered using intensity-modulated radiation
      therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel
      fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged >=65, with
      Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II
      study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy
      in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by
      physician/patient and objectively by using a computer program (BCCT.core) before
      APBR, during, and after completion of the treatment. RESULTS: The median age was
      72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5
      months. The 5-year locoregional control in this cohort was 97% and overall
      survival 87%. At the last follow-up, patients and physicians rated cosmesis as
      'excellent' or 'good' in 100% and 91 %, respectively. The BCCT.core program
      scored the cosmesis as 'excellent' or 'good' in 87% of the patients at baseline
      and 81% at the last follow-up. The median V50 (20 Gy) of the whole breast volume
      (WBV) was 37.2%, with the median WBV V100 (40 Gy) of 10.9%. CONCLUSION: An
      excellent rate of tumor control was observed in this prospective trial. By using
      multiple assessment techniques, we are showing acceptable cosmesis, supporting
      the use of IMRT planned APBR with daily schedule in elderly patients with early
      stage BC.

PMID- 29207865
TI  - Prognostic value of nodal SUVmax of 18F-FDG PET/CT in nasopharyngeal carcinoma
      treated with intensity-modulated radiotherapy.
AB  - PURPOSE: To investigate the predictive role of maximum standardized uptake value
      (SUVmax) of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission
      tomography/computed tomography (PET/CT) in nasopharyngeal cancer patients treated
      with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Between
      October 2006 and April 2016, 53 patients were treated with IMRT in two
      institutions and their PET/CT at the time of diagnosis was reviewed. The SUVmax
      of their nasopharyngeal lesions and metastatic lymph nodes (LN) was recorded.
      IMRT was delivered using helical tomotherapy. All patients except for one were
      treated with concurrent chemoradiation therapy (CCRT). Correlations between
      SUVmax and patients' survival and recurrence were analyzed. RESULTS: At a median
      follow-up time of 31.5 months (range, 3.4 to 98.7 months), the 3-year overall
      survival (OS) and disease-free survival (DFS) rates were 83.2% and 77.5%,
      respectively. In univariate analysis, patients with a higher nodal pre-treatment
      SUVmax (>= 13.4) demonstrated significantly lower 3-year OS (93.1% vs. 55.5%; p =
      0.003), DFS (92.7% vs. 38.5%; p < 0.001), locoregional recurrence-free survival
      (100% vs. 50.5%; p < 0.001), and distant metastasis-free survival (100% vs.
      69.2%; p = 0.004), respectively. In multivariate analysis, high pre-treatment
      nodal SUVmax (>= 13.4) was a negative prognostic factor for OS (hazard ratio
      [HR], 7.799; 95% confidence interval [CI], 1.506-40.397; p = 0.014) and DFS (HR,
      9.392; 95% CI, 1.989-44.339; p = 0.005). CONCLUSIONS: High pre-treatment nodal
      SUVmax was an independent prognosticator of survival and disease progression in
      nasopharyngeal carcinoma patients treated with IMRT in our cohort. Therefore,
      nodal SUVmax may provide important information for identifying patients who
      require more aggressive treatment.

PMID- 29207866
TI  - Interobserver variation in target volume for salvage radiotherapy in recurrent
      prostate cancer patients after radical prostatectomy using CT versus combined CT
      and MRI: a multicenter study (KROG 13-11).
AB  - PURPOSE: To investigate interobserver variation in target volume delineations for
      prostate cancer salvage radiotherapy using planning computed tomography (CT)
      versus combined planning CT and magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: Ten radiation oncologists independently delineated a target volume on
      the planning CT scans of five cases with different pathological status after
      radical prostatectomy. Two weeks later, this was repeated with the addition of
      planning MRI. The volumes obtained with CT only and combined CT and MRI were
      compared, and the effect of the addition of planning MRI on interobserver
      variability was assessed. RESULTS: There were large differences in clinical
      target volume (CTV) delineated by each observer, regardless of the addition of
      planning MRI (9.44-139.27 cm3 in CT only and 7.77-122.83 cm3 in CT plus MRI) and
      no significant differences in the mean and standard deviation of CTV. However,
      there were decreases in mean volume and standard deviation as a result of using
      the planning MRI. CONCLUSION: This study showed substantial interobserver
      variation in target volume delineation for salvage radiotherapy. The combination
      of planning MRI with CT tended to decrease the target volume and the variation.

PMID- 29207868
TI  - Unexpected amyloidosis, mimicking a splenic cyst.

PMID- 29207869
TI  - Concomitant emphysematous cystitis and liver abscess.

PMID- 29207867
TI  - Updated treatment strategies for intestinal Behcet's disease.
AB  - Behcet's disease (BD) is a chronic, idiopathic, relapsing immune-mediated disease
      involving multiple organs, and is characterized by recurrent oral and genital
      ulcers, ocular disease, gastrointestinal ulcers, vascular diseases, and skin
      lesions. In particular, gastrointestinal involvement in BD is followed by severe
      complications, including massive bleeding, bowel perforation, and fistula, which
      can lead to significant morbidity and mortality. However, the management of
      intestinal BD has not yet been properly established. Intestinal BD patients with
      a severe clinical course experience frequent disease aggravations and often
      require recurrent corticosteroid and/or immunomodulatory therapies, or even
      surgery. However, a considerable number of patients with intestinal BD are often
      refractory to conventional therapies such as corticosteroids and
      immunomodulators. Recently, there has been a line of evidence suggesting that
      biologics such as infliximab and adalimumab are effective in treating intestinal
      BD. Moreover, new biologics targeting proteins other than tumor necrosis factor
      alpha are emerging and are under active investigation. Therefore, in this paper,
      we review the current therapeutic strategies and new clinical data for the
      treatment of intestinal BD.

PMID- 29207870
TI  - Thermodynamics of a MU-oxo Dicopper(II) Complex for Hydrogen Atom Abstraction.
AB  - The mono-MU-hydroxo complex {[Cu(tmpa)]2-(MU-OH)}3+ (1) can undergo reversible
      deprotonation at -30  degrees C to yield {[Cu(tmpa)]2-(MU-O)}2+ (2). This species
      is basic with a pKa of 24.3. 2 is competent for concerted proton-electron
      transfer from TEMPOH, but is an intrinsically poor hydrogen atom abstractor
      (BDFE(OH) of 77.2 kcal/mol) based on kinetic and thermodynamic analyses.
      Nonetheless, DFT calculations experimentally calibrated against 2 reveal that
      [Cu2O]2+ is likely thermodynamically viable in copper-dependent methane
      monoxygenase enzymes.

PMID- 29207871
TI  - Molecular Tensor Analysis of Third-Harmonic Scattering in Liquids.
AB  - Third-harmonic scattering is a nonlinear optical process that involves the
      molecular second-hyperpolarizability, gamma. This work presents a rigorous
      quantum electrodynamical analysis of the scattering process, involving a
      partially index-symmetric construction of the fourth-rank gamma tensor-dispensing
      with the Kleinman symmetry condition. To account for stochastic molecular
      rotation in fluids, methods of isotropic averaging must be employed to relate the
      molecular properties to accessible experimental quantities such as depolarization
      ratio. A complete eighth-rank tensor rotational average yields results for
      observable third-harmonic scattering rates, cast as a function of the natural
      invariant gamma components, and the polarization geometry of the experiment.
      Decomposing the tensor gamma into irreducible weights allows specific predictions
      to be made for each molecular point group, allowing greater discrimination
      between the results for different molecular symmetries.

PMID- 29207872
TI  - Complexation of Al3+ and Ni2+ by l-Ascorbic Acid: An Experimental and Theoretical
      Investigation.
AB  - Despite the potential versatility of Vitamin C as a ligand, only for few metal
      complexes does full characterization exist. Vitamin C metal complexes, indeed,
      are difficult to study experimentally because the ligand has multiple protonation
      and oxidation states, and the metal-ligand complexes are in general not as tight
      as one might expect and frequently resistant to crystallographic
      characterization. In most cases, coordination via one of the hypothesized modes
      is invoked, characterized by monodentate or bidentate coordination via the most
      acidic oxygen atoms, with the ligand singly or doubly deprotonated. In this study
      the ability of l-ascorbic acid to form complexes with Al3+ and Ni2+ ions under
      physiological conditions was investigated by using a combination of
      potentiometric measurements, 1H NMR spectroscopy, and DFT computations in order
      to recognize the structural properties of the resulting complexes in aqueous
      solution. The comparison between the values of the free energies of complexation
      obtained by using DFT quantum chemical calculations and estimated from
      experimental stability constants according to the mass action law and by
      considering the involved equilibria allows to select structure and preferred
      coordination modes of formed complexes. The protonation constant of the free
      ligand was also determined using potentiometric data and its reproduction by
      using computational approaches was critically commented.

PMID- 29207873
TI  - A Novel Doxorubicin Prodrug with GRP78 Recognition and Nucleus-Targeting Ability
      for Safe and Effective Cancer Therapy.
AB  - Glucose-regulated protein of 78 kDa (GRP78) has become an attractive and novel
      target for tumor therapy. Design and construction of powerful delivery systems
      that could efficiently transport doxorubicin (DOX) to a tumor-cell nucleus
      remains a formidable challenge for improving the tumor therapeutic index and
      mitigating side effects to normal tissues. Herein, a novel doxorubicin prodrug
      (NDP) with GRP78 recognition and nucleus-targeting ability was synthesized by a
      facile chemical route. NDP exhibited an enhanced antiproliferative activity
      against colorectal cancer cells and could efficiently enter the cell nucleus.
      Furthermore, it is inspiring to note that NDP displayed a much stronger
      inhibitory efficacy against the growth of colorectal cancer xenografts in nude
      mice than free DOX and showed superior in vivo safety. Together, the work
      provides a novel GRP78 and nucleus-targeting strategy, and the NDP holds great
      promise to be used as a potent and safe chemotherapeutic agent.

PMID- 29207874
TI  - Recent Progress in the Chemistry of Pyridazinones for Functional Group
      Transformations.
AB  - While N-hetereocycles have received significant attention in organic synthesis
      and other research fields, the chemistry of pyridazine, a six-membered aromatic
      ring with two adjacent nitrogen atoms, and its derivatives has been relatively
      little understood. This Synopsis describes recent progress made in the synthesis
      of pyridazine derivatives-particularly, pyridazin-3(2H)-ones-and their utility as
      efficient and recyclable functional group carriers for various important organic
      reactions.

PMID- 29207876
TI  - Rural health in Japan: past and future.

PMID- 29207877
TI  - Alternative Thiol-Based Redox Systems.
AB  - The maintenance of thiol-redox homeostasis is vital to the survival of living
      organisms. Sulfur-based low-molecular weight compounds and proteins synthesized
      by cells provide efficient and specific ways to counteract oxidative stress and
      regulate cellular processes. For these tasks, most organisms share the
      glutathione and thioredoxin NADPH-dependent redox systems. However, in certain
      lineages, evolution has taken different paths that led to the emergence of novel
      cysteine-based low-molecular weight redox cofactors, around which new redox
      systems evolved. These include the sugar-based cysteinyl derivatives mycothiol
      and bacillithiol, and ergothioneine (EGT), which are present in different phyla
      from bacteria. Within Eukarya, some fungi contain EGT, whereas trypanothione is
      unique to species from the Euglenozoa family. This Forum compiles the state-of
      the-art knowledge about these noncanonical redox systems of pathogenic organisms.
      The functions in physiology and pathogenicity, as well as structural and
      biochemical specializations that these system components evolved, are thoroughly
      discussed. Antioxid. Redox Signal. 28, 407-409.

PMID- 29207878
TI  - CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies.
AB  - The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected
      T cells with specificity for CD19 induced complete remissions in the majority of
      patients, with a realistic hope for cure. However, recent follow-up data revealed
      a substantial risk of relapse through leukemic cells that lack the CAR targeted
      antigen. In this situation, a bispecific CAR with binding domains for CD19 and
      CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The
      anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of
      CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting
      T-cell activation. T cells with the anti-CD20-CD19 CAR efficiently killed
      patients' chronic lymphocytic leukemia cells in vitro. The bispecific CAR T cells
      cleared pediatric acute lymphocytic leukemia with a mixed CD19+CD20+/CD20-
      phenotype from the blood and bone marrow of transplanted mice, while anti-CD20
      CAR T cells left CD20- leukemic cells behind without curing the disease. Data
      indicate the superior anti-leukemic activity in the control of leukemia, implying
      that the anti-CD20-CD19 bispecific CAR T cells may reduce the risk of relapse
      through antigen-loss leukemic cells in the long term.

PMID- 29207879
TI  - Association of DGAT2 gene polymorphisms with carcass and meat quality traits in
      domestic pigeons (Columba livia).
AB  - 1. Diacylglycerol acyltransferase (DGAT) plays an important role in the synthesis
      of triacylglycerol, but its effects on meat quality and carcass composition in
      pigeons are unclear. In this study, single-nucleotide polymorphisms (SNPs) in the
      exons of the DGAT2 gene were identified and analysed by using DNA sequencing
      methods in 200 domestic pigeons (Columba livia). The associations between DGAT2
      polymorphisms and carcass and meat quality traits were also analysed. 2.
      Sequencing results showed that 5 nucleotide mutations were detected in exons 3,
      4, 5 and 6 of the DGAT2 gene. The analysis revealed three genotypes (AA, AB and
      BB) in G18398T and G22484C, in which the AA genotype and A allele had the highest
      frequency. 3. In the SNP of G18398T located in exon 5, individuals with genotype
      BB had significantly higher meat quality and lower abdominal fat content than
      those with AA or AB genotype. In the SNP of G22484C located in exon 6, the
      genotype AA showed highest carcass trait values, while the genotype BB
      represented better meat quality, compared to AA and AB genotypes. 4. The results
      imply that DGAT2 gene has a close relationship with carcass and meat quality
      traits in pigeons, and the SNPs of G18398T and G22484C can be used as genetic
      markers for marker-assisted breeding in pigeon.

PMID- 29207880
TI  - The psychosocial needs of refugee children and youth and best practices for
      filling these needs: A systematic review.
AB  - Conflict across the globe has displaced over 16.1 million refugees, with
      approximately half under the age of 18. Despite the number of young refugees,
      there is a dearth of research reporting on the needs of refugee children and
      youth. The purpose of this systematic review is to begin to fill this gap by
      summarizing what we know about the needs of refugee children and youth (5-18
      years old). Eighteen manuscripts met the study inclusion criteria. In these
      studies, the identified needs of refugee children and youth were primarily in the
      domains of social support, security, culture, and education. Several strategies
      were identified as facilitating their integration, such as mentorship programs.
      The current review can help inform future integration programs designed for
      refugee children and youth. Supporting the integration of refugee children and
      youth, and their families, promotes positive outcomes and is beneficial for both
      refugees and members of host communities.

PMID- 29207882
TI  - The modified lateral supraorbital approach.
AB  - PURPOSE: Lateral supraorbital approach is a simpler and quicker method than
      pterional approach. It provides a more anterior projection when compared to the
      pterional approach. There are some minor differences of the modified lateral
      supraorbital approach when compared to lateral supraorbital approach. It is
      directed more subfrontally and anterior than the pterional and lateral
      supraorbital approach. MATERIAL AND METHODS: We used modified lateral
      supraorbital approach in 100 cases between 2012 and 2015 in Medical Park Izmir
      Hospital/Turkey. The assessed data were as follows: age, gender, Glasgow coma
      scale at admission, the localization of pathology, the condition of surgical
      obliteration for aneurysm, excision grade for meningioma, length of stay in the
      hospital and Glasgow outcoma scale at discharge. RESULTS: Of all patients, 58
      (58%) were men and 42 (42%) were women. Our cases were anterior communicating
      artery aneurysms (41 cases), tuberculum sella and medial sphenoid wing
      meningiomas (22 cases), middle cerebral artery aneurysms (15 cases), olfactory
      groove meningiomas (15 cases), anterior choroidal artery aneurysms (4 cases) and
      posterior communicating artery aneurysms (3 cases). 4 patients died and the
      mortality rate of the study cohort was 4%. CONCLUSIONS: The MLSA is faster,
      simpler and less invasive than the PA and LSA.

PMID- 29207881
TI  - Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular
      disease.
AB  - INTRODUCTION: Sickle cell disease (SCD) is a devastating monogenic disorder that
      presents as a multisystem illness and affects approximately 100,000 individuals
      in the United States alone. SCD management largely focuses on primary prevention,
      symptomatic treatment and targeting of hemoglobin polymerization and red blood
      cell sickling. Areas covered: This review will discuss the progress of SCD over
      the last few decades, highlighting some of the clinical (mainly cerebrovascular)
      and psychosocial challenges of SCD in the United States. In addition, focus will
      also be made on the evolving science and management of this inherited disease.
      Expert commentary: Until recently hydroxyurea (HU) has been the only FDA approved
      therapy for SCD. However, advancing understanding of SCD pathophysiology has led
      to multiple clinical trials targeting SCD related thrombo-inflammation, abnormal
      endothelial biology, increased oxidant stress and sickle cell mutation. Yet,
      despite advancing understanding, available therapies are limited. SCD also
      imposes great psychosocial challenges for the individual and the affected
      community, which has previously been under-recognized. This has created a
      pressing need for complementary adjuvant therapies with repurposed and novel
      drugs, in addition to the establishment of comprehensive clinics focusing on both
      the medical treatment and the psychosocial issues associated with SCD.

PMID- 29207883
TI  - Physiological and behavioral indices of short-term stress in wild vicunas
      (Vicugna vicugna) in Jujuy Province, Argentina.
AB  - The management of wild vicunas can trigger a stress response that may compromise
      welfare. In Santa Catalina, Jujuy Province, Argentina, indices of short-term
      stress associated with capture, handling, and shearing were studied in 105 wild
      vicunas (Vicugna vicugna). The study included 2 groups (n = 59 and n = 46) of
      wild vicunas captured in 2 consecutive days. Independent variables analyzed
      included sex, restraint time, and groups. Cortisol, creatine kinase, glucose,
      white blood cells, temperature, heart rate, and respiratory frequency were higher
      than published values. Respiratory rate increased during handling and correlated
      with holding time and group size, while heart rate decreased. Packed cell volume
      was higher in females. Cortisol concentrations differed between restraint groups
      and sex and inversely correlated with agonistic behavior. The most common
      behavior was increased vigilance. Sternal recumbency increased over holding time.
      During handling procedures, frequency of sudden movements like kicking and
      attempts to stand increased as restraint time increased. Females vocalized more
      than males. In conclusion, the methods used triggered measurable changes
      suggestive of short-term stress that appeared to be physiologically tolerated by
      the vicunas.

PMID- 29207884
TI  - Mental Health of Refugees and Asylum Seekers: Assessment and Intervention.
AB  - With unprecedented numbers of displaced persons worldwide, mental health
      clinicians in high-income countries will increasingly encounter refugee and
      asylum-seeking patients, many of whom have experienced significant adversity
      before and after their migration. This paper presents a summary of the recent
      evidence on the assessment and treatment of refugees across the lifespan to
      inform clinicians' approaches to care of refugee patients in mental health care
      settings. Assessment and interventions for refugees are grounded in an
      ecosystemic approach which considers not only pre-migratory trauma, but social,
      familial, and cultural determinants of mental health in the host country.
      Evidence for psychotherapy and pharmacological treatments are reviewed,
      highlighting promising interventions while acknowledging that further research is
      needed. Ultimately, serving refugees necessitates a biopsychosocial approach that
      engages clinicians as medical experts, therapists, and advocates.

PMID- 29207885
TI  - The effectiveness of walking versus exercise on pain and function in chronic low
      back pain: a systematic review and meta-analysis of randomized trials.
AB  - OBJECTIVE: Walking is commonly recommended to relieve pain and improve function
      in chronic low back pain. The purpose of this study was to conduct a systematic
      review and meta-analysis of randomized controlled trials concerning the
      effectiveness of walking interventions compared to other physical exercise on
      pain, disability, quality of life and fear-avoidance, in chronic low back pain.
      METHODS: Randomized controlled trials investigating the effects of walking alone
      compared to exercise and to exercise with added walking on adults with chronic
      low back pain were identified using the MEDLINE, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro),
      Cochrane Central Register of Controlled Trials (CENTRAL), PsychINFO, and SPORT
      DiscusTM databases. Two reviewers independently selected the studies and
      extracted the results. Study quality was assessed using the PEDro scale and the
      clinical relevance of each outcome measure was evaluated. RESULTS: Meta-analysis
      of five randomized controlled trials meeting inclusion criteria was performed.
      The effectiveness of walking and exercise at short-, mid-, and long-term follow
      ups appeared statistically similar. Adding walking to exercise did not induce any
      further statistical improvement, at short-term. CONCLUSIONS: Pain, disability,
      quality of life and fear-avoidance similarly improve by walking or exercise in
      chronic low back pain. Walking may be considered as an alternative to other
      physical activity. Further studies with larger samples, different walking
      dosages, and different walking types should be conducted. Implications for
      Rehabilitation Walking is commonly recommended as an activity in chronic low back
      pain. Pain, disability, and fear-avoidance similarly improve by walking or
      exercise. Adding walking to exercise does not induce greater improvement in the
      short-term. Walking may be a less-expensive alternative to physical exercise in
      chronic low back pain.

PMID- 29207886
TI  - Quality characteristics of wheat flour dough and bread containing grape pomace
      flour.
AB  - Wheat bread was enriched with 6%, 10% and 15% dried and milled grape pomace flour
      from two grape cultivars: 'Merlot' and 'Zelen'. Rheological, textural, sensory
      and antioxidant properties of the enriched dough and bread were evaluated, and
      compared to control samples. Grape cultivar had significant impact on the
      rheological characteristics of the dough, and on the sensory and antioxidant
      properties of the final bread. Development time and dough stability were longer
      when 'Merlot' grape pomace flour was added compared to 'Zelen' grape pomace flour
      and the control. Grape pomace flour addition affected bread volume, firmness,
      crumb and crust colour, and odour and taste intensity. Moreover, grape pomace
      flour addition resulted in a stickier and less springy crumb texture, and some
      negative sensorial properties, such as increased intensity of aftertaste and sand
      feeling in the mouth. The phenolic content and antioxidant activity of bread were
      positively correlated with grape pomace flour addition ( r = 0.987, p = 0.01 and
      r = 0.941, p = 0.01 between phenolic content and ferric reducing antioxidant
      power and phenolic content and 2,2-diphenyl-1-picrylhydrazyl, respectively). The
      highest total phenolic contents were 5.92 mg gallic acid equivalents (GAE)/g dw
      for 'Merlot' and 3.65 mg gallic acid equivalents /g dw for 'Zelen', which were
      seen for the bread prepared with the highest grape pomace flour addition (15%).
      The highest antioxidant activity determined by the 2,2-diphenyl-1-picrylhydrazyl
      and ferric reducing antioxidant power assays were seen for the bread prepared
      with the highest 'Merlot' grape pomace flour addition (15%). Dough characteristic
      and sensory profile are strongly influenced by cultivar of grape pomace flour.
      Based on results of sensory profiling, the variety 'Zelen' is suggested for use.

PMID- 29207887
TI  - Burn care and rehabilitation in Australia: health professionals' perspectives.
AB  - OBJECTIVE: To understand health professionals' perspectives of burn care and
      rehabilitation. DESIGN: Qualitative and semi-structured interviews. SETTING:
      Australian burn and rehabilitation units. PARTICIPANTS: Twenty-two clinicians
      working in burns units across disciplines and healthcare settings. RESULTS: The
      data portrayed the health professionals' perspectives of burn care and
      rehabilitation in Australia. Three themes were identified: (1) interprofessional
      collaboration; (2) integrated community care, and (3) empowering patients to self
      care. CONCLUSION: Burn care and rehabilitation remains a complex and a
      challenging area of care with limited access to burn services especially in rural
      and remote areas. Interprofessional training and education of health
      professionals involved with the complex care of burn injury remains a key element
      to support and sustain the long-term rehabilitation requirements for patients and
      their families. Empowering patients to develop independence early in their
      rehabilitation is fundamental to their ongoing recovery. A burns model of care
      that embraces a multidisciplinary collaboration and integrated care across the
      continuum has the potential to positively impact recovery and improve health
      outcomes. Implications for rehabilitation Burn care and rehabilitation remains a
      complex and challenging area of care. Managing the rehabilitation phase after
      burn injury can be as complex as managing the acute phase. Interprofessional
      collaboration, integrated community care, and empowering patients to self-care
      are key elements for sustaining the rehabilitation of adults with burn injuries.

PMID- 29207888
TI  - Effect of oral supplementation of composite leaf extract of medicinal plants on
      biomarkers of oxidative stress in induced diabetic Wistar rats.
AB  - Present study was conducted to evaluate the effect of oral supplementation of
      composite extract of leaves (CLE) of four medicinal plants; Aegle marmelos,
      Ocimum sanctum, Murraya koenigii and Azadirachta indica on markers of oxidative
      stress in brain tissues of alloxan-induced diabetic rats in vivo. Enhanced lipid
      peroxidation, protein oxidation and reduced antioxidative defence systems were
      measured in brain tissues of diabetic rats. Supplementation of CLE, once in a day
      for 35 days significantly (p < .05) protected the peroxidation of lipid,
      oxidation of protein and ameliorated the antioxidant defence in brain tissue of
      diabetic rats. It was observed that the insulin-like effect of CLE was dose
      dependent; higher effect at higher doses. The results of the study suggest that
      supplementation CLE may provide an overall homeostasis and significant neuro
      protection through rescuing brain cells from oxidative abuse and accelerating
      brain antioxidative defence during advanced stage of hyperglycaemia.

PMID- 29207889
TI  - Primary Carcinosarcoma of the Vagina Associated With Differentiated Squamous
      Intraepithelial Neoplasia in a Patient With Complete Uterine Prolapse: Case
      Report and Review of the Literature.
AB  - Vaginal carcinosarcomas (VCSs) are rare and clinically aggressive neoplasms.
      Primary vaginal malignancies are among the rarest malignant tumors, so clear
      management guidelines and optimal therapy, especially in the presence of
      significant pelvic organ prolapse, has not been determined. Here, we present a
      case of primary VCS closely associated with differentiated squamous
      intraepithelial neoplasia (DSIN), from which it appeared to have arisen in a
      postmenopausal patient with complete uterine prolapse. The unusual presentation
      of our case with DSIN in the adjacent vaginal epithelium with possible diagnostic
      pitfalls emphasizes the need for systemic presentation of these cases to help
      pathologists and clinicians know that such lesions can initially present in a
      patient with complete uterine prolapse. To our knowledge, this is the first case
      of vaginal DSIN described in the literature to date.

PMID- 29207890
TI  - Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a
      Transgenic Sheep Model of Huntington's Disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease caused by a
      genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies
      in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but
      evidence for their effectiveness and safety in larger animals is lacking. HD
      transgenic sheep express the full-length human HTT with 73 CAG repeats. AAV9 was
      used to deliver unilaterally to HD sheep striatum an artificial miRNA targeting
      exon 48 of the human HTT mRNA under control of two alternative promoters: U6 or
      CbetaA. The treatment reduced human mutant (m) HTT mRNA and protein 50-80% in the
      striatum at 1 and 6 months post injection. Silencing was detectable in both the
      caudate and putamen. Levels of endogenous sheep HTT protein were not affected.
      There was no significant loss of neurons labeled by DARPP32 or NeuN at 6 months
      after treatment, and Iba1-positive microglia were detected at control levels. It
      is concluded that safe and effective silencing of human mHTT protein can be
      achieved and sustained in a large-animal brain by direct delivery of an AAV
      carrying an artificial miRNA.

PMID- 29207891
TI  - Reluctance of patients with chronic obstructive pulmonary disease in its early
      stages and their families to participate in a partnership-based self-management
      trial: A search for explanation.
AB  - Recruitment, the process of accessing, screening, selecting and retaining
      participants for research remains a challenge. In a randomized controlled trial,
      partnership-based self-management intervention for patients who have chronic
      obstructive pulmonary disease (COPD) in its initial stages, and their families, a
      theoretical framework developed for patients with an advanced COPD and their
      families was modified and implemented in a primary care context. In contrast to
      recruitment to the original study where 4% decline participation, in this study
      25% of the potential patients declined participation. Although participants were
      encouraged to bring a family member, only 25% of them did so. The main reason for
      not being accompanied by a family member was that patients did not want anybody
      accompany them. Those who had quit smoking were more often accompanied by a
      family member compared to those who smoked. Reviewing the literature, the most
      compelling explanations for non-participation are shame and self-blame due to
      smoking, and that potential participants may not have envisioned any benefits
      from participating since they might not have realized that they had COPD. An
      alternative recruitment process needs to embrace the situation that potential
      participants find themselves in and which takes account of the issues at stake.

PMID- 29207892
TI  - Serum adipokines (adiponectin and resistin) correlation in developing gestational
      diabetes mellitus: pilot study.
AB  - Adiponectin and resistin are adipose tissue-derived proteins with antagonistic
      actions; adiponectin has insulin sensitive properties while resistin is involved
      in the development of insulin resistance. We analyzed adiponectin and resistin
      levels in gestational diabetes mellitus (GDM) women to evaluate the association
      of these adipokines in a very high diabetes prevalence population. An age-matched
      case-control study of GDM and normal pregnant women in Saudi population. We
      recruited 90 pregnant women at 24-32 weeks of gestation. Glucose levels (fasting,
      1, 2, and 3 h) and lipid parameters (cholesterol, triglyceride, HDL cholesterol,
      LDL cholesterol) were measured. Serum adiponectin and resistin levels were
      analyzed using Randox evidence biochip analyzer. Pearson's correlation
      coefficient was used to determine the association of adiponectin and resistin
      with GDM risk factors. GDM women showed significantly low adiponectin and high
      resistin levels when compared with control group. Pearson's correlation analysis
      of adiponectin and resistin in all the subjects with various GDM risk factors
      showed a negative association of adiponectin (r = -0.32, p = .05) and a positive
      correlation of resistin (r = 0.41, p = .01) with LDL cholesterol. This study
      analyzes adiponectin and resistin levels together, as accumulating evidences
      shows that these are involved in the pathophysiology of GDM. This is going to
      help to determine in conjunction with traditional risk factors the incremental
      value of circulating adiponectin and resistin in developing GDM.

PMID- 29207893
TI  - A combination of an iron chelator with an antioxidant exerts greater efficacy on
      cardioprotection than monotherapy in iron-overload thalassemic mice.
AB  - Many recent studies have shown that antioxidant compounds decrease cardiac
      oxidative stress, decrease cardiac iron deposition, and improve cardiac
      dysfunction in iron-overload induced cardiomyopathy in animal models.
      Interestingly, a therapy including the combination of the iron chelator
      deferiprone (DFP) plus the antioxidant N-acetylcysteine (NAC) has been shown to
      significantly decrease oxidative stress and restore heart and brain function in
      iron-overloaded rats. However, the cardioprotective effects of this combined DFP
      and NAC treatment in thalassemic mice have not been investigated. We hypothesised
      that the combination of DFP and NAC exerts better cardioprotection than
      monotherapy via decreasing cardiac iron accumulation, oxidative stress, and
      apoptosis in thalassemic mice. The iron-overload condition was induced in
      heterozygous betaKO HT and wild-type mice by instigating high iron diet
      consumption (FE) for three months. Then, iron chelator DFP (75 mg/kg/day twice a
      day), antioxidant NAC (100 mg/kg/day once a day), and combined DFP plus NAC were
      fed via oral gavage for one month with continuous iron feeding. Left ventricular
      (LV) function, heart rate variability (HRV), apoptosis, and cardiac iron
      accumulation were determined. Chronic iron-overload in mice led to increased
      cardiac iron deposition, oxidative stress, apoptosis, and impaired LV function
      and HRV. Although DFP and NAC showed similar cardioprotective efficacy, combined
      DFP plus NAC exerted greater efficacy in reducing both cardiac iron deposition
      and cellular apoptosis than monotherapy. In conclusion, combined iron chelator
      and NAC treatment exert the greatest cardioprotective efficacy when compared with
      either of the monotherapies in iron-overload thalassemic mice.

PMID- 29207894
TI  - Maternal and neonatal outcomes related to iron supplementation or iron status: a
      summary of meta-analyses.
AB  - BACKGROUND: Iron deficiency is the most abundant nutritional deficiency in the
      world and is discussed to be associated with adverse pregnancy outcomes. The
      objective of this review was to perform an umbrella summary of meta-analyses to
      evaluate the effects and associations of iron supplementation or iron status on
      maternal and birth/neonatal outcomes. METHODS: A literature search was conducted
      on PubMed and Scopus by two reviewers without temporal restriction. Systematic
      reviews and meta-analyses of studies evaluating (1) the effects of
      multimicronutrient compared to iron + folic acid supplementations on maternal and
      birth/neonatal outcomes (2), the association of dietary iron intake or hemoglobin
      or ferritin status regarding the risk for maternal (gestational diabetes mellitus
      (GDM)) and birth/neonatal outcomes, and (3) the effects of iron supplementation
      on pregnancy and birth/neonatal outcomes, were included in this review. RESULTS:
      Overall, 16 meta-analyses were included. Multimicronutrient supplements had
      significant risk reducing effects on low birth weight and small for gestational
      age compared to iron/folic acid supplements as controls. Furthermore, most of the
      meta-analyses showed that higher levels of hemoglobin or ferritin increased the
      risk for GDM. On the other hand, maternal anemia (low hemoglobin levels) was
      associated with adverse birth/neonatal outcomes. Finally, iron supplementation
      reduced the risk of iron deficiency and iron deficiency anemia and had some risk
      reducing effects on low birth weight newborns. CONCLUSIONS: Our summary of meta
      analyses showed that multimicronutrient supplementation had beneficial effects on
      some neonatal outcomes. Furthermore, higher ferritin levels seem to increase the
      risk for GDM whereas maternal anemia was associated with adverse birth/neonatal
      outcomes.

PMID- 29207895
TI  - Nonpharmacological management of neonatal abstinence syndrome: a review of the
      literature.
AB  - BACKGROUND: Infants with neonatal abstinence syndrome (NAS) experience withdrawal
      that occurs as a result of termination of placental opioid supply following
      delivery. Common symptoms include restlessness, tremors, agitation and
      gastrointestinal disturbances. Severe NAS is often treated using opioids and/or
      sedatives. Although commonly employed effectively in neonatal care, there is a
      lack of published information regarding nonpharmacological management of the NAS
      infant. OBJECTIVE: The purpose of this review was to summarize the current
      literature on nonpharmacological management of NAS. METHODS: A literature search
      of Medline and EMBASE was performed for articles published between 2000 and June
      2107. RESULTS: Nonpharmacological management encompasses "environmental control",
      "feeding methods", "social integration", "soothing techniques" and "therapeutic
      modalities". Several interventions, including: breastfeeding, swaddling, rooming
      in, environmental control and skin to skin contact have proven to be effective in
      managing NAS and should be incorporated into standard of care for this population
      (Level I-III Evidence). These interventions can be effective when offered in
      combination with pharmacological therapy, or as stand-alone therapy for less
      severe cases of NAS (Finnegan score <8). CONCLUSIONS: Given the increasing body
      of evidence on its efficacy and ease of implementation, nonpharmacological
      treatment should universally be incorporated into standard of care for NAS.

PMID- 29207897
TI  - Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus
      in the Han Chinese population.
AB  - Objective To investigate the association of the CD11b single nucleotide
      polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han
      Chinese patients, and to clarify this association with SLE clinical
      manifestations. Methods PCR-restriction fragment length polymorphism and direct
      sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628
      healthy controls in this case-control study to compare genotype and allele
      frequency distributions. Correlations between CD11b genotypes and clinical
      manifestations were also determined. Results The frequency of the CD11b rs1143679
      GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than
      that of European and American populations, but close to the frequency observed in
      individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also
      shown to confer susceptibility to SLE (odds ratio = 4.00, 95% confidence interval
      = 1.11-14.41). CD11b rs1143679 was found to be significantly associated with
      nephritis, but not with age of disease onset, arthritis, hematological
      involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be
      associated with risk for SLE in the Han Chinese population, and may play an
      important role in the development of lupus nephritis.

PMID- 29207896
TI  - Rho GTPase effectors and NAD metabolism in cancer immune suppression.
AB  - INTRODUCTION: Sustained proliferative signaling and de-regulated cellular
      bioenergetics are two of the chief hallmarks of cancer. Alterations in the Ras
      pathway and its downstream effectors are among the major drivers for uncontrolled
      cell growth in many cancers. The GTPases are one of the signaling molecules that
      activate crucial signal transducing pathways downstream of Ras through several
      effector proteins. The GTPases (GTP bound) interact with several effectors and
      modulate a number of different biological pathways including those that regulate
      cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis,
      transcription and nuclear signaling. Similarly, the altered glycolytic pathway,
      the so-called 'Warburg effect', rewires tumor cell metabolism to support the
      biosynthetic requirements of uncontrolled proliferation. There exists strong
      evidence for the critical role of the glycolytic pathway's rate limiting enzymes
      in promoting immunosuppression. Areas covered: We review the emerging roles of
      GTPase effector proteins particularly the p21 activated kinase 4 (PAK4) and
      nicotinamide biosynthetic pathway enzyme nicotinamide phosphoribosyltransferase
      (NAMPT) as signaling molecules in immune surveillance and the immune response.
      Expert opinion: In this expert opinion article we highlight the recent
      information on the role of GTPases and the metabolic enzymes on the immune
      microenvironment and propose some unique immune therapeutic opportunities.

PMID- 29207899
TI  - Effect of a Mat Pilates Program with TheraBand on Dynamic Balance in Patients
      with Parkinson's Disease: Feasibility Study and Randomized Controlled Trial.
AB  - The aim of this study was to assess the effect of a physical exercise program
      based on Mat Pilates (MP) with TheraBand(r) on the dynamic balance of a sample
      population diagnosed with Parkinson's disease (PD). After random selection, 26
      participants were allocated to a MP group or a control group where they performed
      calisthenics exercises. Both interventions lasted 12 weeks and involved 2 weekly
      sessions of 60 minutes. Assessments took place at baseline, 12 weeks after the
      intervention started and 4 weeks after the intervention was completed using the
      body mass index (BMI), the Timed Up and Go (TUG) test with Wiva(r) sensors, the
      30 Second Chair Stand test, and the Five Times Sit to Stand test. The group that
      completed the MP program presented significant improvements in BMI (F1,21 =
      3.986; p = 0.038), the 30 Second Chair Stand test (F1,21 = 6.716; p = 0.014), the
      Five Times Sit to Stand test (F1,21 = 5.213; p = 0.032), and the time required to
      complete the TUG dynamic balance test (F1,21 = 5.035; p = 0.035). The MP program
      performed by a sample population with PD led to improvements in dynamic balance,
      and participants in the MP group showed increased strength in the lower limbs,
      but such improvements were not permanent after the activity ceased.

PMID- 29207898
TI  - NR3C1 gene polymorphisms are associated with steroid resistance in patients with
      primary nephrotic syndrome.
AB  - AIM: The aim of this study was to investigate the role of SNPs of genes involved
      in the glucocorticoid pathway in the development of steroid resistance in
      patients with primary nephrotic syndrome. METHODS: Sequenom MassARRAY method was
      used to sequence 25 SNP genotypes in 154 patients. The frequency distribution of
      the genotypes was compared between patients with steroid-sensitive nephrotic
      syndrome and those with steroid-resistant nephrotic syndrome. RESULTS: NR3C1
      rs6196 G allele carriers had a decreased risk of steroid resistance compared with
      that of the A allele carriers. The presence of rs10052957 and rs258751 A alleles
      could reduce the incidence of steroid resistance compared with that with G
      allele. Haplotype analysis showed AAG and GGA haplotypes that contain NR3C1
      rs10052957, rs258751 and rs6196 were associated with steroid resistance.
      CONCLUSION: NR3C1 gene polymorphisms are significantly associated with the
      response to glucocorticoids in patients with primary nephrotic syndrome.

PMID- 29207900
TI  - In vivo characterization of a new type of biodegradable starch microsphere for
      transarterial embolization.
AB  - Transarterial embolization is an established minimally invasive treatment for
      solid tumors. Unintended inflammation, foreign body reactions and ischemia
      triggered neoangiogenesis are clinical drawbacks of permanent embolic materials.
      The aim of the current study was to characterize a new type of biodegradable
      starch microsphere with regard to angiographic and histopathological features
      such as patterns of acute arterial occlusion as well as induction of tissue
      necrosis, microsphere biodegradation, and inflammation and foreign body reactions
      during follow-up. Key characteristics of both biodegradable prototypes (L1 and
      L2; prototype groups) were as follows: microspheres are biodegradable by serum
      alpha-amylase, produced from chemically crosslinked potato starch to different
      extents, in a diameter range of ~300-800 um, differing in size distribution and
      featuring a microsphere deformation of ~1%. In vivo transarterial embolization
      with L1 and L2, while applying clinical standard techniques, was performed and
      compared with clinically established permanent microspheres (Embosphere(r)500-700
      and Embosphere(r)700-900; control groups). Twenty-four pig kidneys were embolized
      with the different embolic materials by following the study protocol, and there
      were no technical failures or complications. Parenchymal necrosis with
      interstitial calcification was observed in all kidneys independent of the type of
      embolic material used. Compared with the permanent embolic materials,
      biodegradable microspheres showed complete (L1) or partial (L2) biodegradation
      within one week after transarterial embolization, and induced a comparable (L1)
      or a lower (L2) degree of arterial wall necrosis and a lower degree of
      inflammation and foreign body reactions. In conclusion, the presented new type of
      biodegradable microsphere is promising, and could be further evaluated in terms
      of clinical translation.

PMID- 29207901
TI  - Repeated treatment with the alpha2-adrenoceptor agonist UK-14304 improves
      cognitive performance in middle-age rats: Role of hippocampal Fas-associated
      death domain.
AB  - The cell fate regulator Fas-associated death domain (FADD) balances cell death
      with non-apoptotic actions via its phosphorylated form. A recent study associated
      loss of cortical FADD with cognitive decline and increased risk of clinical
      dementia. Since the activation of cortical alpha2A-adrenoceptors improved memory
      deficits in various animal models of working memory loss, the present study
      evaluated whether UK-14304, an alpha2-adrenoceptor agonist known to acutely
      regulate brain FADD forms, would improve cognitive function in middle-aged rats.
      Sprague-Dawley rats were treated with UK-14304 (0.3 or 1 mg/kg) or saline (1
      mL/kg) for seven days. Cognitive performance was evaluated in the eight-arm
      radial maze. FADD protein content was measured in the prefrontal cortex and
      hippocampus by Western blot analysis. The results showed that UK-14304 (1 mg/kg)
      improved cognitive performance (less time: -310+/-45 s, p=0.025 and fewer errors:
      -2.75+/-1.06, p=0.043 to complete the maze) and increased FADD selectively in the
      hippocampus (+35+/-11%, p=0.029). Interestingly, hippocampal FADD content
      negatively correlated with the time ( r=-0.651, p<0.01) needed to complete the
      maze. Thus, better cognitive scores were associated with higher FADD hippocampal
      content. These results support a role for alpha2-adrenoceptors in ameliorating
      cognition and suggest FADD protein content as a possible correlate for cognitive
      performance.

PMID- 29207903
TI  - Professor Klaus Gartner, 1927-2017.

PMID- 29207904
TI  - Graft-Versus-Host Disease With Early Cytomegalovirus Infection in
      Gastrointestinal Tract Biopsies.
AB  - Gastrointestinal (GI) graft-versus-host disease (GVHD) and cytomegalovirus (CMV)
      infection often simulate each other. However, distinction between GVHD and CMV
      infection is critical in the management of immunosuppression for transplant
      recipients. This study retrospectively reviewed 16 patients diagnosed with GVHD
      from 2010 to 2016 and found 4 cases (25%) coinfected with CMV. Two cases were
      initially diagnosed as GVHD only but found to have CMV infection by serological
      testing within 3 days after immunosuppression treatment for GVHD. The remarkable
      histological feature of CMV infection appeared to be significant acute
      inflammation in addition to apoptotic epithelial injuries, and particularly in an
      early stage of CMV replication, acute inflammation is possibly the only
      detectable feature of CMV infection.

PMID- 29207902
TI  - Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16
      mouse cancer models.
AB  - Murine orthotopic cancer models often require surgery, potentially causing pain
      or distress. However, analgesics are often withheld because they may alter tumour
      development. Two orthotopically implanted cancers were investigated in mice pre
      treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg).
      Tumours were imaged and welfare was assessed using body weight, behaviour and
      nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary
      carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single
      buprenorphine dose appeared beneficial to cancer growth consistency, a second
      cohort of mice additionally received saline or buprenorphine at 12 and 24 h.
      Surgery resulted in increased mammary tumour growth and lung metastases. These
      unwanted effects were lessened by buprenorphine pre-treatment, especially when
      given repeatedly. Mammary tumour-bearing mice became less active and nociceptive
      thresholds declined over time, indicating some discomfort as tumours grew. In
      study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to
      determine whether meloxicam or buprenorphine affected cancer seeding of the
      lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not.
      Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but
      the magnitude of this was insufficient to conclude that there were any
      significant welfare concerns. This study highlights the scientific value in
      utilising non-surgical models, where possible. When surgery must be performed at
      the time of tumour inoculation, the effects of this should be controlled with
      appropriate analgesics to enhance the value and possibly translation of the
      research.

PMID- 29207905
TI  - Incremental Clinical Utility of ADHD Assessment Measures With Latino Families.
AB  - OBJECTIVE: This study examined the incremental clinical utility of parent and
      teacher reports of ADHD symptomatology and functional impairment in Latino youth,
      as well as parent and teacher agreement with the final clinical judgment on a
      diagnostic structured interview. METHOD: Participants included 70 Latino youth
      (47 males, 23 females; M age = 8.13 years, SD = 2.51 years) and their parents and
      teachers; 60 participants were diagnosed with ADHD. Correlations, percent
      agreement, kappas, and regressions were utilized. RESULTS: Results demonstrated
      that teachers agreed with the final clinical judgment more often than did
      parents. Results additionally demonstrated that functional impairment did not
      statistically significantly improve diagnostic models already including ADHD
      symptoms; follow-up analyses were run and are discussed. Finally, results
      demonstrated that teacher reports statistically significantly improved diagnostic
      models already including parent reports. CONCLUSION: The current findings suggest
      the importance of including both parent and teacher reports of both ADHD
      symptomatology and functional impairment when assessing ADHD in Latino youth.

PMID- 29207906
TI  - Synthetic studies on optically active furofuran and diarylbutane lignans.
AB  - Lignans are a large class of naturally occurring secondary metabolites which are
      widely spread within the plant kingdom. Their diverse structures and variety of
      biological activities have fascinated organic chemists. For synthesizing
      optically active lignans, we have developed the novel asymmetric dimerization of
      cinnamic acid derivatives, and applied it to the enantioselective syntheses of
      furofuran lignans (yangambin, sesamin, eudesmin, caruilignan A) and diarylbutane
      lignans (sauriols A and B). This review summarizes the methodology of our
      asymmetric dimerization of cinnamic acid derivatives, and efficient total
      syntheses of furofuran and diarylbutane lignans reported by our and other groups.

PMID- 29207907
TI  - Implementation of a Goal-Directed Mechanical Ventilation Order Set Driven by
      Respiratory Therapists Improves Compliance With Best Practices for Mechanical
      Ventilation.
AB  - PURPOSE: Data regarding best practices for ventilator management strategies that
      improve outcomes in acute respiratory distress syndrome (ARDS) are readily
      available. However, little is known regarding processes to ensure compliance with
      these strategies. We developed a goal-directed mechanical ventilation order set
      that included physician-specified lung-protective ventilation and oxygenation
      goals to be implemented by respiratory therapists (RTs). We sought as a primary
      outcome to determine whether an RT-driven order set with predefined oxygenation
      and ventilation goals could be implemented and associated with improved adherence
      with best practice. METHODS: We evaluated 1302 patients undergoing invasive
      mechanical ventilation (1693 separate episodes of invasive mechanical
      ventilation) prior to and after institution of a standardized, goal-directed
      mechanical ventilation order set using a controlled before-and-after study
      design. Patient-specific goals for oxygenation partial pressure of oxygen in
      arterial blood (Pao2), ARDS Network [Net] positive end-expiratory pressure
      [PEEP]/fraction of inspired oxygen [Fio2] table use) and ventilation (pH, partial
      pressure of carbon dioxide) were selected by prescribers and implemented by RTs.
      RESULTS: Compliance with the new mechanical ventilation order set was high: 88.2%
      compliance versus 3.8% before implementation of the order set ( P < .001).
      Adherence to the PEEP/Fio2 table after implementation of the order set was
      significantly greater (86.0% after vs 82.9% before, P = .02). There was no
      difference in duration of mechanical ventilation, intensive care unit (ICU)
      length of stay, and in-hospital or ICU mortality. CONCLUSIONS: A standardized
      best practice mechanical ventilation order set can be implemented by a
      multidisciplinary team and is associated with improved compliance to written
      orders and adherence to the ARDSNet PEEP/Fio2 table.

PMID- 29207908
TI  - A Scoping Review of Pain in Children after Traumatic Brain Injury: Is There More
      Than Headache?
AB  - Headache is a common source of pain in children after traumatic brain injury
      (TBI); however, relatively little is known about nonheadache pain in this
      pediatric population. The present review seeks to map the extant literature to
      determine the prevalence, characteristics, and impact of nonheadache pain in
      children post-TBI of all severities. We found that of 109 studies published on
      pain in children after a TBI, 95 (87%) were focused exclusively on headache pain
      and only 14 (13%) reported on nonheadache pain or overall pain, with half (n = 7)
      in the form of case studies. Overall, the level of evidence was low, with only
      three level 1 high-quality prospective studies. In one study, over half (57.1%)
      of adolescents who experienced persistent pain post-TBI reported pain in multiple
      body sites (e.g., back, lower limb, and neck).1 For each additional noncephalic
      pain site, the risk for developing chronic migraine is also increased.
      Nevertheless, pain in body regions other than the head is often not assessed
      systematically in pediatric TBI research. Findings of the current review suggest
      that pain assessment in children post-TBI needs improvement, given that pain is
      linked to worse recovery, poorer quality of life, and can be long-lasting. More
      rigorous examination of nonheadache pain and its role in impeding recovery in
      children post-TBI is imperative and has the potential to improve the care and
      management of children with TBI. We conclude with recommendations for pain
      assessment, discuss gaps in the literature, and highlight directions for future
      research.

PMID- 29207909
TI  - The Evolving Role of Long-Term Pharmacotherapy for Opioid-Induced Constipation in
      Patients Being Treated for Noncancer Pain.
AB  - Nationally, the prescription of opioids for acute and chronic pain is increasing.
      As opioid use continues to expand and become of increased concern for health-care
      practitioners, so do the adverse effects and long-term management of those
      effects. Opioid-induced constipation (OIC) presents a unique challenge because
      tolerance does not develop to this particular adverse effect, making chronic pain
      management a delicate balance between relieving pain and preventing long-term
      adverse effects such as constipation and dependence. Several agents have been
      developed for the treatment of OIC in patients with chronic noncancer pain on the
      basis of short-term studies of 12 weeks or less. However, chronic pain management
      often extends beyond this 12-week boundary, resulting in health-care
      professionals questioning the safety and efficacy of continued treatment with OIC
      agents. This review evaluates available literature on long-term treatment of OIC
      in patients with chronic noncancer pain with lubiprostone, naloxegol, and
      methylnaltrexone as well as preliminary results of the recently completed
      naldemedine long-term trial, COMPOSE-3.

PMID- 29207910
TI  - The Posture of Putting One's Palms Together Modulates Visual Motion Event
      Perception.
AB  - We investigated the effect of an observer's hand postures on visual motion
      perception using the stream/bounce display. When two identical visual objects
      move across collinear horizontal trajectories toward each other in a two
      dimensional display, observers perceive them as either streaming or bouncing. In
      our previous study, we found that when observers put their palms together just
      below the coincidence point of the two objects, the percentage of bouncing
      responses increased, mainly depending on the proprioceptive information from
      their own hands. However, it remains unclear if the tactile or haptic (force)
      information produced by the postures mostly influences the stream/bounce
      perception. We solved this problem by changing the tactile and haptic information
      on the palms of the hands. Experiment 1 showed that the promotion of bouncing
      perception was observed only when the posture of directly putting one's palms
      together was used, while there was no effect when a brick was sandwiched between
      the participant's palms. Experiment 2 demonstrated that the strength of force
      used when putting the palms together had no effect on increasing bounce
      perception. Our findings indicate that the hands-induced bounce effect derives
      from the tactile information produced by the direct contact between both palms.

PMID- 29207911
TI  - Soybean amplifies the hypohomocysteinemic effect of betaine and improves its
      hypercholesterolemic effect.
AB  - We examined whether soybean (SB) and soy protein isolate (SPI) can prevent the
      betaine-induced elevation of plasma cholesterol as well as maintain the betaine
      induced reduction of plasma Hcy concentration. Rats were fed casein-, SB-, or SPI
      based diet with or without betaine; SPI-based diet with betaine containing
      soybean fiber (SF) or soy lecithin (SL) or the combination of SF and SL. Plasma
      Hcy concentration was decreased by feeding betaine to rats fed the casein-, SB-,
      and SPI-based diets. Betaine-induced elevation of plasma cholesterol was
      decreased by feeding the SB-based diet compared with the casein-based diet, but
      was not decreased by feeding the SPI-based diet. In rats fed the SPI-based diet,
      the increased concentration of plasma cholesterol by betaine feeding was not
      prevented by independent addition of SL or SF, but was prevented by a combination
      of SL and SF, and was associated with increased fecal excretion of bile acids.

PMID- 29207913
TI  - Generation of Dopamine-Secreting Cells from Human Adipose Tissue-Derived Stem
      Cells In Vitro.
AB  - Several studies have demonstrated the differentiation of human adipose tissue
      derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the
      fate of these cells toward dopaminergic neurons has not been frequently reported.
      The aim of this study was to investigate dopaminergic specification of hADSCs in
      vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were
      characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog,
      fibroblast growth factor 8, basic fibroblast growth factor, and brain-derived
      neurotrophic factor were used under a low serum condition. As the control group,
      the ADSCs were cultured under the same low serum condition without the
      dopaminergic cocktail. At the end of differentiation period, the cells expressed
      neuron-specific markers, NES, NSE, and NEFL, and dopaminergic markers, EN1,
      NURR1, PITX3, VMAT2, TH, and GIRK2 genes. TH, NURR1, and EN1 mRNAs were
      upregulated in the dopaminergic group compared with the control group. NEFL and
      TH proteins were also expressed in the differentiated cells. A total of 27.9% of
      the cells differentiated in dopaminergic induction medium showed positive
      staining for TH protein. Based on reversed-phase high-performance liquid
      chromatography analysis, the differentiated cells released a significant amount
      of dopamine in response to KCl-induced depolarization. In conclusion, results of
      this study indicate that hADSCs can be induced by a growth factor cocktail to
      produce dopamine secreting cells with possible applications for future cell
      replacement therapy of Parkinson's disease.

PMID- 29207912
TI  - Genome-wide scan identifies candidate loci related to remifentanil requirements
      during laparoscopic-assisted colectomy.
AB  - AIM:  Opioids are widely used as effective analgesics, but opioid sensitivity is
      well known to vary widely among individuals. We explored the genetic factors that
      contribute to individual differences in intraoperative opioid sensitivity by
      performing a genome-wide association study. PATIENTS & METHODS: We conducted a
      multistage genome-wide association study in subjects who underwent laparoscopic
      assisted colectomy. RESULTS: A nonsynonymous SNP, rs199670311, within the TMEM8A
      gene region and intronic SNPs, including rs4839603, within the SLC9A9 gene region
      were significantly associated with intraoperative opioid requirements (p = 3.409
      * 10-8 in the dominant model for rs199670311; p = 4.162 * 10-6 and p = 4.229 * 10
      6 in the additive and recessive models, respectively, for rs4839603). The A and T
      alleles of the rs199670311 and rs4839603 SNPs, respectively, were associated with
      lower opioid sensitivity in patients. CONCLUSION: Our findings provide valuable
      information for personalized pain treatment during laparoscopic-assisted
      colectomy.

PMID- 29207914
TI  - Exploring School Nurse Interventions and Health and Education Outcomes: An
      Integrative Review.
AB  - School nurses intervene with students, parents, and school staff to advance the
      health and academic success of students. We conducted an integrative literature
      review of published research to describe the types of school nurse interventions
      and health and education outcome measures and to examine how school nurse
      interventions were linked to student outcomes. Sixty-five studies met the
      inclusion criteria. We used the National Association of School Nurses' Framework
      for 21st Century School Nursing Practice to categorize school nurse interventions
      and health and education outcome measures. The majority of interventions were
      categorized under the care coordination principle, most commonly, motivational
      interviewing and counseling. In 17 studies, school nurse interventions were
      linked to improved student outcomes. Most studies (80%) were descriptive. To
      advance school nursing science, researchers can build on this foundation with
      more rigorous research methods to evaluate the impact of school nurse
      interventions and activities on student health and education outcomes.

PMID- 29207915
TI  - First synthesis of (S)-(+)-hymenoic acid, a DNA polymerase lambda inhibitor
      isolated from Hymenochaetaceae sp.
AB  - Hymenoic acid, isolated from cultures of the fungus, Hymenochaetaceae sp., is a
      specific inhibitor of DNA polymerase lambda. The first synthesis of (S)-(+)
      hymenoic acid was achieved by starting from trans-1,4-cyclohexanedimethanol and
      methyl (R)-(-)-3-hydroxyisobutyrate, and Julia-Kocienski olefination was employed
      as the key step.

PMID- 29207916
TI  - Flavonoid glycosides in Malabar spinach Basella alba inhibit the growth of
      Spodoptera litura larvae.
AB  - Basella alba is a perennial plant of the Basellaceae and is known by various
      common names including Malabar spinach. There are few insects that cause damage
      to B. alba. In this study, we examined the effect of B. alba leaves on the growth
      of Spodoptera litura larvae. B. alba leaves and a methanolic extract of the
      leaves inhibited the growth of S. litura larvae. Half of the larvae reared on the
      leaves died within 1 week. We found that two flavonoids, vitexin, and vitexin-2"
      O-arabinofuranoside, were abundant in the methanol extract of leaves. When larvae
      were reared on purified vitexin or vitexin-2"-O-arabinofuranoside, their growth
      was significantly impaired compared with larvae reared on control spinach leaves.
      These results suggested that the flavonoid glycosides in B. alba leaves act as
      deterrents to S. litura larvae.

PMID- 29207917
TI  - Functional Effects of SNPs in MYH9 and Risks of Nonsyndromic Orofacial Clefts.
AB  - Nonsyndromic orofacial clefts (NSOCs) are congenital newborn malformations.
      Myosin heavy chain 9 ( MYH9) is a candidate gene of NSOCs. To investigate the
      associations between single-nucleotide polymorphisms (SNPs) of MYH9 and NSOC
      susceptibility, a 2-stage case-control study was designed and 4 potentially
      functional SNPs of MYH9 (rs12107, rs2269529, rs9619601, rs5756130) were selected
      and genotyped by iPLEX Sequenom MassARRAY and TaqMan assay in the first stage
      (599 NSOC cases and 590 controls). The significant SNPs in the first stage were
      replicated in the second stage (676 NSOC cases and 705 controls) by TaqMan assay.
      Reverse transcription polymerase chain reaction, cell transfection, and
      luciferase assay were performed accordingly to explore their functionality. In
      stage I, rs12107 was nominally associated with NSOCs, whereas rs2269529 showed a
      significant association (rs12107: Phet = 0.028; rs2269529: Phet = 0.001). In
      stage II, rs12107 was nominally associated with NSOCs, and rs2269529 showed a
      significant association (rs12107: Phom = 0.014; rs2269529: Phet = 0.006). In
      combined stages, these 2 SNPs gained significant associations (rs12107: Pdom =
      0.004; rs2269529: Pdom = 4.4 * 10-5). In subphenotype analysis, these 2 SNPs were
      associated with cleft lip only (CLO) and cleft lip with palate (CLP), and
      rs2269529 was also associated with cleft palate only (CPO). Haplotype analysis
      revealed associations between rs12107-G/rs2269529-T and NSOC susceptibility ( P =
      0.011). Combined analysis of rs12107 and rs2269529 indicated the risk of NSOCs
      increased with the number of risk alleles (rs12107-G and rs2269529-T, P for trend
      = 0.008). MYH9 SNP rs12107 AG + GG and rs2269529 CT + TT were associated with
      higher MYH9 expression in lip tissues compared with their corresponding wild-type
      homozygote. For rs12107, higher luciferase activities of G allele than A allele
      were observed in the luciferase assay. MYH9 was downregulated when transfecting
      its putative binding target miR-196b-3p into human embryo plate mesenchyme (HEPM)
      and C2C12 cell lines. For rs2269529, C > T contributed to increased MYH9
      messenger RNA. In conclusion, rs12107 and rs2269529 were associated with the
      expression of MYH9 and contributed to the susceptibility of NSOCs.

PMID- 29207918
TI  - Intake of green-plant membrane with dietary oil suppresses postprandial
      hypertriglyceridemia in rats via promoting excretion of bile acids.
AB  - Green-plant membrane is a phytonutrient present in green leafy vegetables at high
      concentration. Postprandial increases in blood triglyceride levels result in
      insulin resistance and type 2 diabetes. Additionally, dietary life and eating
      order also affect postprandial hypertriglyceridemia. In this study, the effects
      of once-daily intake of green-plant membrane with dietary oil on postprandial
      hypertriglyceridemia were investigated in vitro and in vivo. In vitro, green
      plant membrane bound hydrophobic bile acids but did not inhibit pancreatic lipase
      activity. Following the administration, green-plant membrane with dietary oil in
      rats, oral fat tolerance tests, increases in serum triglycerides levels were
      significantly reduced. Moreover, fecal total lipid and bile acid volumes were
      significantly increased in rats that administered 200 mg/mL green-plant membrane.
      These results suggest that green-plant membrane with dietary oil inhibits dietary
      fat absorption via promotion of bile acid excretion in feces and the
      effectiveness of eating green-plant membrane, such as green leafy vegetables,
      with meals.

PMID- 29207919
TI  - Enhancement of natural killer activity and IFN-gamma production in an IL-12
      dependent manner by a Brassica rapa L.
AB  - Certain food components possess immunomodulatory effects. The aim of this study
      was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa
      L. We demonstrated an enhancement of natural killer (NK) activity and interferon
      (IFN)-gamma production in mice that were orally administered an insoluble
      fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced
      IFN-gamma production in mouse spleen cells in an interleukin (IL)-12-dependent
      manner, and NK1.1+ cells were the main cells responsible for producing IFN-gamma.
      Additionally, the results suggested that the active compounds in the insoluble
      fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin
      receptors on dendritic cells, and they activated signaling cascades such as MAPK,
      NF-kappaB, and Syk. These findings suggest that B. rapa L. is a potentially
      promising immuno-improving material, and it might be useful for preventing
      immunological disorders such as infections and cancers by activating innate
      immunity.

PMID- 29207920
TI  - Endoscopic ultrasound guided versus surgical transrectal drainage of pelvic
      abscesses.
AB  - BACKGROUND: Pelvic abscesses are common but only small case series reporting
      outcome of either endoscopic ultrasound (EUS) guided or surgical transrectal
      drainage have been reported. METHODS: We performed a retrospective consecutive
      cohort study, assessing effectivity and safety of EUS guided or surgical
      transrectal drainage of previously untreated pelvic abscesses from all causes,
      diagnosed using CT scan between 09/2010 and 06/2014 in a Dutch teaching hospital.
      RESULTS: Forty-six patients with comparable demographics, apart from stoma
      presence (p = .016), were included. The success rate after a single intervention
      was 83% in the EUS guided compared to 48% in the surgical transrectal drainage
      group (p = .013). However, the mean duration of drainage was threefold in the EUS
      group [42 versus 13 days (p = .001)]. The length of stay in hospital was similar
      for both EUS and surgical group [24 versus 20 days (p = .56)] as was abscess
      resolution during follow-up [78% versus 74%]. We recorded a total of 12
      anastomotic leaks [3 versus 9]. In the occurrence of leakage, only one stoma was
      finally closed in each group. CONCLUSION: EUS guided and surgical transrectal
      drainage of pelvic abscesses from any cause are safe, nonetheless EUS guided
      drainage(if feasible) seems more effective after a single treatment, with high
      overall cure rates.

PMID- 29207922
TI  - Effect of steady-state methadone on high fructose corn syrup consumption in rats.
AB  - Patients undergoing methadone maintenance treatment self-report enhanced
      preferences for, and excessive consumption of, foods rich in sugar. However, it
      is unclear whether these are direct pharmacological effects of methadone or the
      consequences of metabolic dysfunctions induced by addiction to illicit opiates.
      Hence, the current study in drug-naive male Sprague-Dawley rats explored the
      effects of steady-state methadone delivered by osmotic mini-pumps (13 days; 0,
      10, 30 mg/kg/day) on consumption of rat chow and a palatable, sweet, liquid high
      fructose corn syrup solution. Six days after the removal of the pumps, mRNA
      expression of genes involved in responses to stress and rewards were quantified:
      pro-opiomelanocortin in the hypothalamus, mu-opioid receptor in the nucleus
      accumbens, and dopamine D2 receptor in the dorsal striatum. Taste reactivity and
      locomotion tests were also performed throughout the study. It was found that
      methadone increased caloric intake from high fructose corn syrup and reduced
      caloric intake from chow, effects that could not be directly ascribed to changes
      in high fructose corn syrup taste reactivity or motor functions. However, the
      changes in caloric intake displayed significant tolerance, and mRNA expression
      analysis suggested that methadone attenuated the effect of high fructose corn
      syrup on pro-opiomelanocortin mRNA, and possibly on dopamine D2 receptor mRNA.
      These findings in rats suggest that the pharmacological effect of methadone,
      administered to achieve steady-state maintenance, may not be the primary cause of
      dietary alterations reported by patients maintained on methadone.

PMID- 29207921
TI  - Allyl isothiocyanate increases carbohydrate oxidation through enhancing insulin
      secretion by TRPV1.
AB  - The transient receptor potential (TRP) V1 is a cation channel belonging to the
      TRP channel family and it has been reported to be involved in energy metabolism,
      especially glucose metabolism. While, we have previously shown that intragastric
      administration of allyl isothiocyanate (AITC) enhanced glucose metabolism via
      TRPV1, the underlying mechanism has not been elucidated. In this study, we
      examined the relationship between insulin secretion and the increase in
      carbohydrate oxidation due to AITC. Intragastric administration of AITC elevated
      blood insulin levels in mice and AITC directly enhanced insulin secretion from
      isolated islets. These observations were not reproduced in TRPV1 knockout mice.
      Furthermore, AITC did not increase carbohydrate oxidation in streptozotocin
      treated mice. These results suggest that intragastric administration of AITC
      could induce insulin secretion from islets via TRPV1 and that enhancement of
      insulin secretion was related to the increased carbohydrate oxidation due to
      AITC.

PMID- 29207923
TI  - Isogloiosiphone B, a novel acetal, and hydrophobic compounds as beta
      glucuronidase inhibitors derived from the red alga Neodilsea yendoana.
AB  - A novel acetal named isogloiosiphone B was isolated from the red alga Neodilsea
      yendoana, along with three known hydrophobic compounds as beta-glucuronidase
      inhibitors. The acetal was determined as a naturally occurring compound from the
      extraction experiments with several kinds of solvent. The acetal showed the
      highest inhibition against beta-glucuronidase among the compounds examined.

PMID- 29207924
TI  - Speckle Tracking in Transcranial Ultrasound Allows Noninvasive Analysis of
      Pulsation Patterns of the Third Ventricle.
AB  - Cerebrospinal fluid (CSF) flow is sensitive to many cerebral disorders. We aimed
      to develop a noninvasive bedside method to detect physiological and pathological
      CSF phenomena by measuring pulsation patterns of the third ventricle. By
      transcranial B-mode ultrasound, electrocardiography (ECG)-gated video loops of
      the third ventricle were acquired. "Speckle tracking" software was used to
      quantify the relative change of its width. We conducted measurements of nine
      cardiac cycles in 11 healthy subjects in sitting and in supine position during
      Valsalva maneuver to investigate the influence of an increased intracranial
      pressure on the relative deformation of the third ventricle. In one patient with
      occlusive hydrocephalus, 19 cardiac cycles were measured in sitting position
      before and after removal of a tumorous obstruction of the aqueduct of Sylvius.
      Healthy subjects expressed a pulse-related increased width of the third ventricle
      ([Formula: see text]: +5.69, 95% confidence interval [CI] = [4.38, 7.00]). No
      significant difference was found between the sitting and the supine position in
      healthy adults. In the preoperative state of occlusive hydrocephalus, we found a
      negative, pulse-related deformation ([Formula: see text]: -1.86, 95% CI = [-2.15,
      -1.58]) with delayed onset. After surgery, the deformation pattern resembled that
      of our healthy controls. The difference between pre- and postoperative condition
      was significant (p < 0.001). Transcranial B-mode sonography can be used to record
      small movements of the sidewalls of the third ventricle. This noninvasive bedside
      method is suitable to assess CSF pulsatility within the third ventricle and might
      be able to distinguish between physiological and pathological flows.

PMID- 29207925
TI  - Quantifying emergency department crowding: comparison between two scores.
AB  - INTRODUCTION: Emergency department (ED) crowding is a major international concern
      with a negative impact on both patient care and providers. Currently, there is no
      consensus regarding measure of crowding. Therefore, emergency physicians have to
      choose between numerous scoring systems, from simple to more complex. The aim of
      the present study was to compare the complex National Emergency Department
      Overcrowding Scale (NEDOCS) with the simple ED Occupancy rate (OR) determination.
      We further evaluated the correlation between these scores and a qualitative
      assessment of crowding. METHOD: This study was conducted in two academic and one
      regional hospital in Liege Province, in Belgium; each accounting for an ED census
      of over 40,000 patient visits per year. Crowding measures were sampled four times
      a day, over a two-week period, in January 2016. RESULTS: ED staff considered
      overcrowding as a major concern in the three ED. Median OR ranged from 68 to 100,
      while NEDOCS ranged from 64.5 to 76.3. A significant correlation was found in
      each ED between the OR and the NEDOCS (Pearson r = 0.973, 0.974 and 0.972), as
      well as between the OR, the NEDOCS and the subjective evaluation by the ED staff
      (p = 0.001). CONCLUSION: Crowding evaluation in ED requires validated scores. Our
      study in three different hospitals demonstrates that simple OR appeared as
      accurate as more sophisticated NEDOCS. Furthermore, this measure is perfectly
      correlated with the feeling of ED staff.

PMID- 29207926
TI  - Nature-derived epigallocatechin gallate/duck's feet collagen/hydroxyapatite
      composite sponges for enhanced bone tissue regeneration.
AB  - Scaffolds mimicking structural and chemical characteristics of the native bone
      tissues are critical for bone tissue engineering. Herein, we have developed and
      characterized epigallocatechin gallate/duck's feet collagen/hydroxyapatite
      (EGCG/DC/HAp) composite sponges that enhanced the bone tissue regeneration. The
      three-dimensional composite sponges were synthesized by loading various amounts
      (i.e. 1, 5 and 10 MUM) of EGCG to duck feet derived collagen followed by freeze
      drying and then coating with hydroxyapatite. Several measuremental techniques
      were employed to examine the properties of the as-fabricated composite sponges
      including morphology and structure, porosity, compressive strength, etc. and as
      well compared with pristine duck feet derived collagen. SEM observations of
      EGCG/DC/HAp sponges showed the formation of a highly porous collagen matrix with
      EGCG embodiment. The porosity and pore size of sponges were found to increase by
      high EGCG content. The compressive strength was calculated as 3.54 +/- 0.04, 3.63
      +/- 0.03, 3.89 +/- 0.05, 4.047 +/- 0.05 MPa for 1, 5 and 10 MUM EGCG/DC/HAp
      sponges, respectively. Osteoblast-like cell (BMSCs isolated from rabbit) culture
      and in vivo experiments with EGCG/DC/HAp sponges implanted in nude mouse followed
      by histological staining showed enhanced cell internalization and attachment,
      cell proliferation, alkaline phosphatase expressions, indicating that EGCG/DC/HAp
      sponges have ahigh biocompatibility. Moreover, highEGCG content in the
      EGCG/DC/HAp sponges have led to increased cellular behavior. Collectively, the 5
      MUM of EGCG/DC/HAp sponges were suggested as the potential candidates for bone
      tissue regeneration.

PMID- 29207927
TI  - Welcome to the 13th Volume of Nanomedicine.

PMID- 29207928
TI  - Occupational gender composition and mild to severe depression in a Swedish
      cohort: The impact of psychosocial work factors.
AB  - AIMS: The aim of the present study was to investigate associations between
      occupational gender composition, psychosocial work factors and mild to severe
      depression in Swedish women and men with various educational backgrounds.
      METHODS: The study included 5560 participants from two waves of the Swedish
      Longitudinal Occupational Survey of Health, an approximately representative
      sample of the Swedish working population. Odds ratios (OR) and 95% confidence
      intervals of mild to severe depression in 2014 were estimated for five strata of
      occupational gender composition with >20-40%, >40-60%, >60-80% and >80-100%
      women, using 0-20% women as the reference. Analyses were stratified by gender and
      education. Job strain, organisational injustice, poor social support and effort
      reward imbalance in 2012 were added in separate models, and changes in OR of mild
      to severe depression for strata of occupational gender composition were
      evaluated. RESULTS: Among women, the odds of mild to severe depression did not
      vary by occupational gender composition. Among men with low to intermediate
      education, the odds were higher in the stratum with >80-100% women, and among men
      with high education, the odds were higher in strata with >20-40% and >60-80%
      women. Psychosocial work factors affected the odds ratios of mild to severe
      depression, but most of the variation remained unexplained. CONCLUSIONS: Odds of
      mild to severe depression appeared to vary by occupational gender composition
      among Swedish men but not women. This variation seemed only to a small extent to
      be explained by psychosocial work factors.

PMID- 29207929
TI  - A nationwide Danish survey on the use of green spaces by people with mobility
      disabilities.
AB  - BACKGROUND: There is increasing awareness of the importance and health benefits
      of living near green spaces. Research usually focuses on the general population's
      use of green spaces and there has been little focus on the use of green spaces by
      specific groups, such as people with mobility disabilities. This represents a
      significant knowledge gap with regard to facilitating access to healthy green
      environments by all population groups. This study aims to provide knowledge of
      the use of green spaces by people with mobility disabilities. METHODS: The study
      was based on data from the Danish Health and Morbidity Survey in 2005. The study
      participants consisted of 11,238 adult Danes, 383 of whom reported mobility
      disabilities, meaning that they were dependent on assistive devices for walking
      or moving around. Multiple logistic regression analysis was used to investigate
      the association between mobility disability and use of green spaces. RESULTS: The
      results show that respondents who reported mobility disabilities visited green
      spaces less often than respondents without mobility disabilities. The severity of
      the mobility disability was associated with the frequency of visits. Frequency of
      visits was also related to the respondents' health-related quality of life
      status. CONCLUSIONS: These results highlight the need for further research into
      the constraints faced by people with mobility disabilities with regard to
      visiting green spaces.

PMID- 29207930
TI  - The rise and fall of an opt-out system.
AB  - INTRODUCTION: In Denmark, citizens participate in register-based research without
      the possibility of opting out. However, in 1995 it was made possible for Danish
      citizens to register an opt-out called 'researcher protection' [
      forskerbeskyttelse], which implied that researchers could not contact people to
      invite them to participate in research projects, such as clinical trials or
      questionnaries, based on their registrations in national registers. Data already
      registered could still be used for research. In 2014, this possibility of opt-out
      was revoked by law. AIMS: The aims of this paper are to understand how the Danish
      researcher protection system came about, why it was terminated and what we can we
      learn from this example. METHODS: We conducted a descriptive analysis of a copy
      of the former researcher protection register along with policies and media debate
      surrounding the rise and revocation of the researcher protection system. RESULTS:
      Our results show how both the inception and the abolishment of researcher
      protection appear to be ad hoc and without specified criteria of success. An
      examination of the recorded entries in the researcher protection registry could
      have led to changes in its administration as an alternative to its total
      abolition. CONCLUSIONS: In future opt-out systems, there should be focus on
      monitoring register practices and the purpose and criteria for evaluation must be
      defined prior to implementation.

PMID- 29207931
TI  - Drug-related deaths: Statistics based on death certificates miss one-third of
      cases.
AB  - AIMS: Statistics on drug-related deaths (DRD) provide crucial information on the
      drug situation. The European Monitoring Centre for Drug and Drug Addiction
      (EMCDDA) has published a specification for extracting DRD from national mortality
      registers to be used in international comparisons. However, surprisingly little
      is known of the accuracy of DRD statistics derived from national mortality
      registers. This study assesses the accuracy of Swedish data derived from national
      mortality registers by comparing it with other sources of data. METHODS: We
      compared five Swedish datasets. Three were derived from national mortality
      registers, two according to a Swedish specification and one according to the
      EMCDDA specification. A fourth dataset was based on toxicological analyses. We
      used a fifth dataset, an inventory of DRD in Stockholm, to assess the
      completeness and coverage of the Swedish datasets. RESULTS: All datasets were
      extracted from high-quality registers, but still did not capture all DRD, and
      both the numbers and demographic characteristics varied considerably. However,
      the time trends were consistent between the selections. In international
      comparisons, data completeness and investigation procedures may impact even more
      on stated numbers. CONCLUSIONS: Basing international comparisons on numbers or
      rates of DRDs gives misleading results, but comparing trends is still meaningful.

PMID- 29207932
TI  - Contact with primary and mental health care prior to suicide: A systematic review
      of the literature from 2000 to 2017.
AB  - AIM: To examine rates of contact with primary and mental health care prior to
      suicide in men and women and across a range of age categories. METHOD: The
      authors performed a systematic review of 44 studies from 2000 to 2017 of which 36
      reported rates on contact with primary health care and 14 reported on contact
      with mental health care prior to suicide. RESULTS: Contact with primary health
      care was highest in the year prior to suicide with an average contact rate of
      80%. At one month, the average rate was 44%. The lifetime contact rate for mental
      health care was 57%, and 31% in the final 12 months. In general, women and those
      over 50 years of age had the highest rates of contact with health care prior to
      suicide. CONCLUSIONS: Contact with primary health care prior to suicide is common
      even in the final month before death. The findings presented in this study
      highlight the importance of placing suicide prevention strategies and
      interventions within the primary health care setting.

PMID- 29207933
TI  - Prognostic factors for in-hospital mortality of patients hospitalized for acutely
      decompensated heart failure.
AB  - Objectives Despite improved treatment during last 20 years, prognosis for
      patients hospitalized for acutely decompensated heart failure (ADHF) is poor and
      mortality rates reported for these patients are high. Laboratory results can
      assist clinicians in evaluation and triaging of patients on hospital admission,
      and are important for the medical decision-making and prognosis assessments.
      Recently, new guidelines for the diagnosis and treatment of acute and chronic HF
      patients were published introducing a new group of patients with mid-range left
      ventricular ejection fraction (LVEF). Methods In order to explore the prognostic
      value for the in-hospital mortality of ADHF patients we analyzed laboratory test
      results for 165 emergency hospitalized patients regarding the survival and LVEF.
      Results In-hospital mortality was 16%. Patients who died were older than
      survivals (p = 0.003). There were no differences in LVEF between survivals and
      non-survivals. Patients who survived had significantly lower N-terminal pro-B
      type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs
      cTnT), uric acid, urea, creatinine, and red blood cell distribution width (RDW)
      than patients who died (p < 0.001). All these tests had a good discrimination
      power between survivals and non-survivals (p < 0.001), but their incremental
      addition to NT-proBNP didn't improve its overall prognostic value. There was only
      a very weak correlation between NT-proBNP concentrations and LVEF. Groups with
      different LVEF status showed significant difference in number of erythrocytes,
      RDW and hemoglobin concentrations. Conclusions NT-proBNP had the best
      discriminatory power between survivals and non-survivals. Some routine laboratory
      test results, like RDW, uric acid, urea, and creatinine, have potentially
      significant value.

PMID- 29207934
TI  - Incidence of skeletal related events in patients with bone metastasis receiving
      denosumab every four weeks compared to intervals greater than every four weeks.
AB  - Objective Denosumab is a monoclonal antibody used for prevention of skeletal
      related events in patients with bone metastasis from solid tumors and is
      administered every four weeks. In our practice, denosumab is often given at
      different frequencies more similar to patient's chemotherapy regimens to decrease
      frequency of clinic visits. The purpose of this study is to compare the incidence
      of skeletal related events, incidence of hypocalcemia, and cost with denosumab
      given at every four weeks and denosumab given at other frequencies. Methods This
      retrospective study at Duke University Health System included solid tumor
      patients with an age >=18 years who received denosumab for prevention of skeletal
      related events. Results A total of 94 patients were included, with 29 in the
      every four-week group and 65 in the greater than every four-week group. Patients
      who received denosumab every four weeks had a 41.4% incidence of skeletal related
      events compared to 26.2% incidence of skeletal related events in patients who
      received denosumab at intervals greater than every four weeks (OR: 0.50; p =
      0.14). There was no statistically significant difference in incidence of
      hypocalcemia. Based on average wholesale price, when the frequency of denosumab
      is extended to greater than every four weeks, annual cost savings per patient
      ranged from $4700 (every 5 weeks) to $18,800 (every 12 weeks). Conclusion While
      this study raises the possibility of decreasing the frequency of denosumab
      administration, further data are necessary to confirm that less frequent
      administration is non-inferior to every four-week administration.

PMID- 29207935
TI  - Cardiac birth defects in a twin infant born to a woman with chronic myeloid
      leukemia on dasatinib.
AB  - Preclinical animal studies have demonstrated an association between maternal use
      of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical
      case series have reported normal pregnancy outcomes and healthy infants in women
      on these medications during the course of their pregnancy. We describe a case of
      a woman with chronic myeloid leukemia who had taken the second-generation
      tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic
      diamniotic twin pregnancy and subsequently delivered two low-birth weight
      infants, one with severe cardiac malformations and the other without apparent
      birth abnormalities. To our knowledge, this is the first reported case of fetal
      cardiovascular defects in an infant born to a woman on dasatinib during a twin
      pregnancy and supports current recommendations to avoid this medication during
      pregnancy. We also review relevant preclinical and clinical studies of tyrosine
      kinase inhibitor use during pregnancy and explore alternative therapeutic options
      for patients with chronic myeloid leukemia during pregnancy to aid clinicians in
      the appropriate management of these patients so as to minimize both maternal and
      fetal risks.

PMID- 29207936
TI  - Fatal graft-versus-host disease after allogeneic stem cell transplantation in a
      patient recently exposed to nivolumab.
AB  - Allogeneic hematopoietic stem cell transplantation and checkpoint blockade
      therapy are immune-based salvage therapies for Hodgkin's lymphoma; however, the
      use of programmed death 1 blocking agents in the allogeneic stem cell
      transplantation setting could augment the incidence of steroid refractory graft
      versus-host disease. Few studies suggest that that nivolumab is safe in patients
      previously treated with an allogeneic stem cell transplantation. Likewise, there
      are very limited data on the use of nivolumab before allogeneic stem cell
      transplantation. Here, we report a case of fatal graft-versus-host disease in a
      patient who underwent allogeneic stem cell transplantation 26 days after the last
      administration of nivolumab. Careful monitoring and close clinical assessment of
      atypical presentation for graft-versus-host disease in these patients, interval
      of time from nivolumab administration to allogeneic stem cell transplantation,
      drug dosage adjustments or more effective allo prophilaxys should been evaluated
      in prospective clinical trial.

PMID- 29207937
TI  - A retrospective analysis of clinical acuity markers on hospital length of stay in
      patients with febrile neutropenia.
AB  - Objective The primary objective of this study was to identify factors that have
      predictive value in determining total hospital length of stay in patients with
      febrile neutropenia, particularly time to first antibiotic dose. Methods This
      study was a retrospective chart review analyzing patients admitted to a 443 bed
      tertiary county teaching hospital from 1 November 2010 through 1 November 2015.
      Patients were eligible for enrollment into the study if they met Infectious
      Diseases Society of America accepted criteria for febrile neutropenia. Results
      Ninety-three patients were included for analysis. Time to first antibiotic dose,
      first empirically appropriate antibiotic dose, and time to first isolate
      appropriate antibiotic did not show a significant correlation to total hospital
      length of stay (p = 0.71, p = 0.342, and p = 0.77, respectively). Subject's
      Multinational Association for Supportive Care in Cancer and Simplified Acute
      Physiology II scores were significantly correlated with hospital lengths of stay
      (p = 0.0052, rs = -0.243 and p = 0.0001, rs = 0.344, respectively). Higher median
      (interquartile ranges) Simplified Acute Physiology II scores were also associated
      with hospital mortality [dead = 46 (34.8-51.7) vs. alive = 34 (28-43.3), p =
      0.0173]. Conclusions Measures of patient acuity, such as the Multinational
      Association for Supportive Care in Cancer and Simplified Acute Physiology II
      scores, did show a correlation to clinical outcomes in patients with febrile
      neutropenia. Timing of initial antibiotics between 2.32 and 6.27 hours after
      presentation in patients with febrile neutropenia did not correlate with clinical
      outcomes.

PMID- 29207938
TI  - Characterization of collaborative practice agreements held by hematopoietic stem
      cell transplant pharmacists.
AB  - Background Current workforce shortages within the hematopoietic stem cell
      transplant field necessitate capitalizing on the role of oncology-trained
      pharmacists. Working within an agreed-upon protocol, pharmacists are able to
      expand patient care delivery through optimal medication therapy management.
      Methods An electronic survey was developed by the Advocacy & Policy Working
      Committee of the American Society for Blood and Marrow Transplantation Pharmacy
      Special Interest Group and distributed to pharmacists involved in the care of
      hematopoietic stem cell transplant patients. The primary objective was to assess
      the current state of collaborative practice agreements in the hematopoietic stem
      cell transplant setting. Results Forty-eight responses representing 41
      institutions were returned. Respondents were mostly female (67%) and practiced in
      the adult setting (83%). Reponses represented a range of practice experience in
      hematopoietic stem cell transplant with the majority of the hematopoietic stem
      cell transplant positions (83%) funded by the department of pharmacy at an
      academic medical center. Of the 48 responses, 22 (46%) respondents reported
      having collaborative practice agreements in place; 10 (21%) respondents did not
      currently have collaborative practice agreements, but were planning to implement
      them; and 16 (33%) respondents did not have collaborative practice agreements at
      their institution. Clinical activities performed under a collaborative practice
      agreement included medication selection and dosing modifications, therapeutic
      drug monitoring, supportive care management, and management of comorbid
      conditions and chronic diseases. The most commonly cited barrier to establishing
      collaborative practice agreements was the inability to secure reimbursement for
      services provided. No respondents reported a negative impact on job satisfaction.
      Conclusions The results of this survey provide the pharmacy community with a
      robust understanding of the current landscape of hematopoietic stem cell
      transplant pharmacy collaborative practice agreements.

PMID- 29207939
TI  - Tocilizumab for the management of immune mediated adverse events secondary to PD
      1 blockade.
AB  - Background Immune checkpoint inhibitors are poised to revolutionize the
      management of a growing number of malignancies. Unfortunately, the management of
      steroid-refractory immune mediated adverse events is based on a paucity of
      randomized data and limited to single center experiences. Our initial experience
      with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a
      wide variety of irAEs. As a result, we adopted the use of tocilizumab for the
      management of steroid refractory irAEs. Methods The character and clinical course
      of irAEs were abstracted from the medical record and analyzed. The dose of
      tocilizumab was 4 mg/kg given IV over one hour. C-reactive protein was drawn at
      first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical
      improvement was defined as either: documentation of resolution of symptoms or
      hospital discharge within seven days. Results Of the initial 87 patients that
      were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were
      on corticosteroids. The majority (88.2%) were lung cancer patients. The index
      grade 3/4 irAE was pneumonitis in 35.3%, serum sickness/SIRS in 35.3%, cerebritis
      in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and
      immune mediated coagulopathy. Median time between first nivolumab and initiation
      of tocilizumab was 76 days (range 1-429). There was a statistically significant
      increase in C-reactive protein from a median of 23 mg/L (range 0.1-238.5) at
      baseline to 109.3 mg/L (21.5-350.4) at the time of index irAE, followed by a
      decrease to 19.2 mg/L (0.25-149) after tocilizumab ( p < 0.00001). Clinical
      improvement was noted in 27/34 patients (79.4%). Some patients (52.9%) required a
      single dose, while 38.2% required two, 8.8% required three and 1 patient required
      four doses. Twenty-seven doses were given in the inpatient setting (49.1%).
      Median time to discharge was four days (range 1-27). Seventy-four percent of
      patients were discharged home. For the 53 doses of tocilizumab that were
      delivered when infliximab was an option, there was a cost savings of $141,048.72
      (WAC) during the 18 month study period. Conclusions Tocilizumab may be a
      therapeutic option for the management of steroid refractory irAEs secondary to
      immune checkpoint blockade. However, randomized trials are needed to better
      elucidate the relative efficacy and safety of these agents.

PMID- 29207940
TI  - Time trend of clinical cases of Lyme disease in two hospitals in Belgium, 2000
      2013.
AB  - BACKGROUND: As several studies indicated an increase in Lyme disease (LD),
      notably in neighbouring countries, concerns have arisen regarding the evolution
      of Lyme disease in Belgium. In order to confirm or infirm the increase of LD in
      Belgium, we focused on hospital admissions of patients diagnosed with LD between
      2000 and 2013 based on hospital admission databases from two hospitals in
      Belgium. METHODS: Hospital databases are a stable recording system. We did a
      retrospective analysis of the medical files of patients hospitalized with Lyme
      disease in two Belgian hospitals between 2000 and 2013. RESULTS: The annual
      number of cases of LD for the two studied Belgian hospitals remained stable
      between 2000 and 2013, ranging from 1 for the Cliniques universitaires Saint-Luc
      to 15 for the the Clinique Saint-Pierre. No increasing trend were noted in the
      estimated annual incidence rate but the average estimated annual incidence rate
      was higher for the hospital Saint-Pierre (8.1 +/- 3.7 per 100,000 inhabitants)
      than Saint-Luc (2.2 +/- 1.5 per 100,000 inhabitants). The number of hospital
      cases of LD peaked between June and November. CONCLUSIONS: Based on hospital
      admissions with LD, no increasing trend was observed for the period 2000-2013 in
      the two studied Belgian hospitals. This is in line with other studies carried out
      in Belgium.

PMID- 29207941
TI  - Uneven acute non-alcoholic fatty change of the liver after percutaneous
      transhepatic portal vein embolization in a patient with hilar cholangiocarcinoma 
      a case report.
AB  - BACKGROUND: Portal vein embolization is essential for patients with biliary
      cancer who undergo extended hepatectomy to induce hypertrophy of the future
      remnant liver. Over 830 patients have undergone the portal vein embolization at
      our institution since 1990. Non-alcoholic fatty liver disease is an entity of
      hepatic disease characterized by fat deposition in hepatocytes. It has a higher
      prevalence among persons with morbid obesity, type 2 diabetes, and
      hyperlipidemia. Neither the mechanism of hepatic hypertrophy after portal vein
      embolization nor the pathophysiology of non-alcoholic fatty liver disease has
      been fully elucidated. Some researchers integrated the evident insults leading to
      progression of fatty liver disease into the multiple-hit hypothesis. Among these
      recognized insults, the change of hemodynamic status of the liver was never
      mentioned. CASE PRESENTATION: We present the case of a woman with perihilar
      cholangiocarcinoma who received endoscopic biliary drainage and presented to our
      institute for surgical consultation. A left trisectionectomy with caudate
      lobectomy and extrahepatic bile duct resection was indicated for curative
      treatment. To safely undergo left trisectionectomy, she underwent selective
      portal vein embolization of the liver, in which uneven acute fatty change
      subsequently developed. The undrained left medial sector of the liver with
      dilated biliary tracts was spared the fatty change. The patient underwent planned
      surgery without any major complications 6 weeks after the event and has since
      resumed a normal life. The discrepancies in fatty deposition in the different
      sectors of the liver were confirmed by pathologic interpretations. CONCLUSION:
      This is the first report of acute fatty change of the liver after portal vein
      embolization. The sparing of the undrained medial sector is unique and
      extraordinary. The images and pathologic interpretations presented in this report
      may inspire further research on how the change of hepatic total inflow after
      portal vein embolization can be one of the insults leading to non-alcoholic fatty
      liver disease/ change.

PMID- 29207942
TI  - A reconstruction of sexual modes throughout animal evolution.
AB  - BACKGROUND: Although most extant animals have separate sexes, simultaneous
      hermaphrodites can be found in lineages throughout the animal kingdom. However,
      the sexual modes of key ancestral nodes including the last common ancestor (LCA)
      of all animals remain unclear. Without these data, it is difficult to infer the
      reproductive-state transitions that occurred early in animal evolution, and thus
      a broad understanding of the evolution of animal reproduction remains elusive. In
      this study, we use a composite phylogeny from four previously published studies,
      two alternative topologies (ctenophores or sponges as sister to the rest of
      animals), and multiple phylogenetic approaches to conduct the most extensive
      analysis to date of the evolution of animal sexual modes. RESULTS: Our analyses
      clarify the sexual mode of many ancestral animal nodes and allow for sound
      inferences of modal transitions that have occurred in animal history. Our results
      also indicate that the transition from separate sexes to hermaphroditism has been
      more common in animal history than the reverse. CONCLUSIONS: These results
      provide the most complete view of the evolution of animal sexual modes to date
      and provide a framework for future inquiries into the correlation of these
      transitions with genes, behaviors, and physiology. These results also suggest
      that mutations promoting hermaphroditism have historically been more likely to
      invade gonochoristic populations than vice versa.

PMID- 29207943
TI  - Auxiliary diagnostic potential of ventricle geometry and late gadolinium
      enhancement in left ventricular non-compaction; non-randomized case control
      study.
AB  - BACKGROUND: There are still ambiguities existing in regard to left ventricular
      non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze
      diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry
      in patients with LVNC and controls. METHODS: Data on cardiac magnetic resonance
      imaging (CMR) studies for LVNC were reassessed from the hospital's database (3.75
      years; n=1975 exams). Matching sample of controls included cases with no
      structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic
      right ventricular dysplasia or subacute myocarditis. Eccentricity of the left
      ventricle was measured at end diastole in the region with pronounced NC and
      maximal to minimal ratio (MaxMinEDDR) was calculated. RESULTS: Study included 255
      patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied
      period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5%
      (95%-CI:42.3-62.5), specificity of 80.4% (95%-CI:73.2-86.5) for LVNC, area under
      curve (AUC) 0.664 (95%-CI:0.603-0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity
      of 95.0% (95%-CI:88.7-98.4), specificity of 82.6% (95%-CI: 75.7-88.2) for LVNC,
      AUC 0.917 (95%-CI:0.876-0.948); p<0.001. LGE correlated with Max-Min-EDD-R
      (Rho=0.130; p=0.038) and there was significant difference in ROC analysis
      DeltaAUC0.244 (95%-CI:0.175-0.314); p<0.001. LGE also correlated negatively with
      stroke volume and systolic function (both p<0.05, respectively). CONCLUSIONS: LGE
      was found to be frequently expressed in patients with LVNC, but without
      sufficient power to be used as a discriminative diagnostic parameter. Both LGE
      and eccentricity of the left ventricle were found to be relatively solid
      diagnostic landmarks of complex infrastructural and functional changes within the
      failing heart.

PMID- 29207944
TI  - Incidence of breast cancer in Chinese women exposed to the 1959-1961 great
      Chinese famine.
AB  - BACKGROUND: The association of malnutrition in early life with breast cancer risk
      has been studied in Europe by investigating survivors of the Dutch Hunger Winter
      Famine, but not in China. We evaluated the effect of exposure to the 1959-1961
      Great Leap Forward famine on subsequent breast cancer risk in Chinese women.
      METHODS: A total of 59,060 women born in 1955~1966 were recruited from Minhang
      district, Shanghai, China, during the period 2008 to 2012. A baseline survey was
      conducted to collect demographic characteristics and known risk factors for
      breast cancer. Incident breast cancers were identified by conducting record
      linkage with the Shanghai Cancer Registry up to June 30, 2015, and confirmed
      through medical records. Cumulative probabilities of cancer incidence were
      evaluated after adjusting for age, educational level and other confounders. Cox
      regression models were applied to estimate the hazard ratios (HR) and 95%
      confidence intervals (CI) of breast cancer. RESULTS: The overall crude incidence
      of in situ and invasive breast cancer were 19.2 and 115.0 per 100,000,
      respectively, in women conceived or born during the famine (1959-1962), slightly
      higher than those in women born before (1955-1958) (13.2 and 109.8/100,000) and
      after (1963-1966) (10.4 and 101.5/100,000). Particularly, at age group of 50-52
      years when all participants contributed person-year of observations, the age
      specific incidence of invasive breast cancer was higher in pre-natal exposed
      women (123.7/100,000, 95%CI: 94.5-161.9/100,000) than in post-natal exposed
      (109.6/100,000, 95%CI: 69.1-174.0/100,000) and unexposed women (82.7/100,000,
      95%CI: 46.9-145.7/100,000). However, the incidence of cancer in situ was slightly
      lower in pre-natal exposed women at the age group. Adjusted cumulative
      probabilities of breast cancer incidence, both in-situ and invasive, were also
      observed to be higher in women exposed to the famine, however, the difference was
      not statistically significant. CONCLUSION: Our results suggest a possible
      adverse, but limited, impact of exposure to the Great famine on the risk of
      breast cancer in Chinese women.

PMID- 29207945
TI  - Meningococcal arthritis and myopericarditis: a case report.
AB  - BACKGROUND: We report the first adult case of Neisseria meningitidis W-135
      presenting with meningococcal arthritis and myopericarditis concomitantly,
      without other classical features of meningococcal disease. CASE PRESENTATION: A
      67-year-old Caucasian man presented with acute-onset polyarthralgia, myalgia, and
      fever. On examination he had polyarticular synovitis. An electrocardiogram (ECG)
      demonstrated ST-elevation in leads I, II, III, aVF, and V2-V6 without reciprocal
      depression, and a high-sensitivity troponin level was significantly elevated.
      Cardiac magnetic resonance (CMR) imaging on day five of admission demonstrated
      patchy pericardial enhancement. Neisseria meningitidis W-135 was isolated from
      both synovial fluid and blood cultures. The clinical outcome was favourable with
      intravenous ceftriaxone and myopericarditis treatment (colchicine and ibuprofen).
      CONCLUSIONS: We conclude that this is a rare case of disseminated Neisseria
      meningitidis W-135 presenting with acute polyarticular septic arthritis and
      myopericarditis, without other classical features of systemic meningococcal
      disease. The earlier described entity of primary meningococcal arthritis (PMA)
      can present in patients with meningococcal bacteraemia, and may not be distinct
      from disseminated meningococcal disease, but rather an atypical presentation of
      this.

PMID- 29207946
TI  - Achieved systolic blood pressure in older people: a systematic review and meta
      analysis.
AB  - BACKGROUND: It remains unclear into which level the systolic blood pressure (SBP)
      should be lowered in order to provide the best cardiovascular protection among
      older people. Hypertension guidelines recommendation on attaining SBP levels <150
      mmHg in this population is currently based on experts' opinion. To clarify this
      issue, we systematically reviewed and quantified available evidence on the impact
      of achieving different SBP levels <150 mmHg on various adverse outcomes in
      subjects aged >=60 years old receiving antihypertensive drug treatment. METHODS:
      We searched 8 databases to identify randomized controlled trials (RCTs) and post
      hoc analyses or subanalyses of RCTs reporting the effects of attaining different
      SBP levels <150 mmHg on the risk of stroke, acute myocardial infarction, heart
      failure, cardiovascular mortality and all-cause mortality in participants aged
      >=60 years. We performed random-effects meta-analyses stratified by study design.
      RESULTS: Eleven studies (> 33,600 participants) were included. Compared with
      attaining SBP levels >=140 mmHg, levels of 130 to <140 mmHg were not associated
      with lower risk of outcomes in the meta-analysis of RCTs, whereas there was an
      associated reduction of cardiovascular mortality (RR 0.72, 95% CI 0.59-0.88) and
      all-cause mortality (RR 0.86, 95% CI 0.75-0.99) in the meta-analysis of post-hoc
      analyses or subanalyses of RCTs. Limited and conflicting data were available for
      the SBP levels of <130 mmHg and 140 to <150 mmHg. CONCLUSIONS: Among older
      people, there is suggestive evidence that achieving SBP levels of 130 to <140
      mmHg is associated with lower risks of cardiovascular and all-cause mortality.
      Future trials are required to confirm these findings and to provide additional
      evidence regarding the <130 and 140 to <150 mmHg SBP levels.

PMID- 29207947
TI  - Modeling heterogeneous (co)variances from adjacent-SNP groups improves genomic
      prediction for milk protein composition traits.
AB  - BACKGROUND: Accurate genomic prediction requires a large reference population,
      which is problematic for traits that are expensive to measure. Traits related to
      milk protein composition are not routinely recorded due to costly procedures and
      are considered to be controlled by a few quantitative trait loci of large effect.
      The amount of variation explained may vary between regions leading to
      heterogeneous (co)variance patterns across the genome. Genomic prediction models
      that can efficiently take such heterogeneity of (co)variances into account can
      result in improved prediction reliability. In this study, we developed and
      implemented novel univariate and bivariate Bayesian prediction models, based on
      estimates of heterogeneous (co)variances for genome segments (BayesAS). Available
      data consisted of milk protein composition traits measured on cows and de
      regressed proofs of total protein yield derived for bulls. Single-nucleotide
      polymorphisms (SNPs), from 50K SNP arrays, were grouped into non-overlapping
      genome segments. A segment was defined as one SNP, or a group of 50, 100, or 200
      adjacent SNPs, or one chromosome, or the whole genome. Traditional univariate and
      bivariate genomic best linear unbiased prediction (GBLUP) models were also run
      for comparison. Reliabilities were calculated through a resampling strategy and
      using deterministic formula. RESULTS: BayesAS models improved prediction
      reliability for most of the traits compared to GBLUP models and this gain
      depended on segment size and genetic architecture of the traits. The gain in
      prediction reliability was especially marked for the protein composition traits
      beta-CN, kappa-CN and beta-LG, for which prediction reliabilities were improved
      by 49 percentage points on average using the MT-BayesAS model with a 100-SNP
      segment size compared to the bivariate GBLUP. Prediction reliabilities were
      highest with the BayesAS model that uses a 100-SNP segment size. The bivariate
      versions of our BayesAS models resulted in extra gains of up to 6% in prediction
      reliability compared to the univariate versions. CONCLUSIONS: Substantial
      improvement in prediction reliability was possible for most of the traits related
      to milk protein composition using our novel BayesAS models. Grouping adjacent
      SNPs into segments provided enhanced information to estimate parameters and
      allowing the segments to have different (co)variances helped disentangle
      heterogeneous (co)variances across the genome.

PMID- 29207948
TI  - Homozygous GRID2 missense mutation predicts a shift in the D-serine binding
      domain of GluD2 in a case with generalized brain atrophy and unusual clinical
      features.
AB  - BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of
      disorders that may present with isolated ataxia, or ataxia in combination with
      other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2
      mutations were recently reported in rare cases with cerebellar syndrome and
      variable degree of ataxia, ocular symptoms, hypotonia and developmental delay.
      CASE PRESENTATION: We report on a consanguineous family with autosomal recessive
      childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor
      development in three siblings. MRI of an adult and affected family member
      revealed slightly widened cerebral and cerebellar sulci, suggesting generalized
      brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we
      identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in
      GRID2 that segregates with the disease. The missense variant is located in a
      conserved region encoding the extracellular serine-binding domain of the GluD2
      protein and predicts a change in conformation of the protein. CONCLUSION: The
      widespread supratentorial brain abnormalities, absence of oculomotor symptoms,
      increased peripheral muscle tone and the novel missense mutation add to the
      clinical and genetic variability in GRID2 associated cerebellar syndrome. The
      neuroradiological findings in our family indicate a generalized neurodegenerative
      process to be taken into account in other families segregating complex clinical
      features and GRID2 mutations.

PMID- 29207949
TI  - Comparative analysis of avian poxvirus genomes, including a novel poxvirus from
      lesser flamingos (Phoenicopterus minor), highlights the lack of conservation of
      the central region.
AB  - BACKGROUND: Avian poxviruses are important pathogens of both wild and domestic
      birds. To date, seven isolates from subclades A and B and one from proposed
      subclade E, have had their genomes completely sequenced. The genomes of these
      isolates have been shown to exhibit typical poxvirus genome characteristics with
      conserved central regions and more variable terminal regions. Infection with
      avian poxviruses (APVs) has been reported in three species of captive flamingo,
      as well as a free-living, lesser flamingo at Kamfers dam, near Kimberley, South
      Africa. This study was undertaken to further characterise this virus which may
      have long term effects on this important and vulnerable, breeding population.
      RESULTS: Gene content and synteny as well as percentage identities between
      conserved orthologues was compared between Flamingopox virus (FGPV) and the other
      sequenced APV genomes. Dotplot comparisons revealed major differences in central
      regions that have been thought to be conserved. Further analysis revealed five
      regions of difference, of differing lengths, spread across the central, conserved
      regions of the various genomes. Although individual gene identities at the
      nucleotide level did not vary greatly, gene content and synteny between
      isolates/species at these identified regions were more divergent than expected.
      CONCLUSION: Basic comparative genomics revealed the expected similarities in
      genome architecture but an in depth, comparative, analysis showed all avian
      poxvirus genomes to differ from other poxvirus genomes in fundamental and
      unexpected ways. The reasons for these large genomic rearrangements in regions of
      the genome that were thought to be relatively conserved are yet to be elucidated.
      Sequencing and analysis of further avian poxvirus genomes will help characterise
      this complex genus of poxviruses.

PMID- 29207950
TI  - Persistent hematuria in patients with antineutrophil cytoplasmic antibody
      associated vasculitis during clinical remission: chronic glomerular lesion or low
      grade active renal vasculitis?
AB  - BACKGROUND: Whether persistent hematuria in patients with antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV) during clinical remission
      reflects active disease or chronic glomerular injury is uncertain. This study
      aimed to investigate the significance of persistent hematuria during clinical
      remission in a large cohort of AAV patients. METHODS: A cohort of 219 AAV
      patients in complete clinical remission after induction therapy at our center was
      retrospectively studied, and their clinical and laboratory data as well as long
      term outcomes were analyzed. RESULTS: A total of 80 out of 219 patients had
      persistent hematuria during clinical remission of AAV. Compared with patients
      without hematuria during remission, the slope of eGFR decline in patients with
      persistent hematuria was significantly higher during the long-term follow-up [3.6
      (IQR 1.2, 7.2) vs. 1.5 (IQR 0.2, 4.0) mL/min/1.73 m2/year, P < 0.001]. Among the
      80 patients with persistent hematuria during remission, there was little
      difference between those with fast and slow decline of eGFR, as divided by either
      median or interquartile range of the slope of eGFR decline. We also compared
      patients without hematuria who had a slope of eGFR decline that was lower than
      the median level of the slope of eGFR decline with those with persistent
      hematuria, and found that patients with hematuria had significantly lower levels
      of CRP and ESR at baseline and higher levels of ANCA at remission. CONCLUSIONS:
      Among the AAV patients who achieved clinical remission after immunosuppressive
      therapy, those with persistent hematuria are not rare and may reflect either
      chronic renal damage or low-grade active renal disease.

PMID- 29207951
TI  - Downstream mediators of Ten-m3 signalling in the developing visual pathway.
AB  - BACKGROUND: The formation of visuotopically-aligned projections in the brain is
      required for the generation of functional binocular circuits. The mechanisms
      which underlie this process are unknown. Ten-m3 is expressed in a broad high
      ventral to low-dorsal gradient across the retina and in topographically
      corresponding gradients in primary visual centres. Deletion of Ten-m3 causes
      profound disruption of binocular visual alignment and function. Surprisingly, one
      of the most apparent neuroanatomical changes-dramatic mismapping of ipsilateral,
      but not contralateral, retinal axons along the representation of the nasotemporal
      retinal axis-does not correlate well with Ten-m3's expression pattern, raising
      questions regarding mechanism. The aim of this study was to further our
      understanding of the molecular interactions which enable the formation of
      functional binocular visual circuits. METHODS: Anterograde tracing, gene
      expression studies and protein pull-down experiments were performed. Statistical
      significance was tested using a Kolmogorov-Smirnov test, pairwise-fixed random
      reallocation tests and univariate ANOVAs. RESULTS: We show that the ipsilateral
      retinal axons in Ten-m3 knockout mice are mismapped as a consequence of early
      axonal guidance defects. The aberrant invasion of the ventral-most region of the
      dorsal lateral geniculate nucleus by ipsilateral retinal axons in Ten-m3
      knockouts suggested changes in the expression of other axonal guidance molecules,
      particularly members of the EphA-ephrinA family. We identified a consistent down
      regulation of EphA7, but none of the other EphA-ephrinA genes tested, as well as
      an up-regulation of ipsilateral-determinants Zic2 and EphB1 in visual structures.
      We also found that Zic2 binds specifically to the intracellular domain of Ten-m3
      in vitro. CONCLUSION: Our findings suggest that Zic2, EphB1 and EphA7 molecules
      may work as effectors of Ten-m3 signalling, acting together to enable the wiring
      of functional binocular visual circuits.

PMID- 29207952
TI  - Economic burden of preemptive treatment of CMV infection after allogeneic stem
      cell transplantation: a retrospective study of 208 consecutive patients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global
      concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They
      affect survival, both by direct and indirect effects. Due to safety issues of
      current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and
      the most common strategy to decrease the incidence of CMV disease is preemptive.
      New, less toxic, molecules are currently being assessed for CMV prophylaxis which
      should replace or considerably decrease the preemptive approach. The aim of this
      study was to assess the economic burden of CMV episodes after HSCT with a
      preemptive approach. METHODS: We analyzed data from 208 consecutive adults
      transplanted in our institution, between 2008 and 2013. Hospital resource
      utilization was retrieved via the linked hospital admissions and Diagnostic
      Related Groups for the period of conditioning to 12 months after transplant.
      RESULTS: CMV episodes occurred in 70 patients (34%) over the first 12 months
      following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total
      length of stay was significantly associated with the occurrence of a CMV episode
      (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre
      transplant CMV serology of donors/recipients nor with survival. The mean cost of
      transplant was ?104,016 (SD = ?37,281) after 12 months. Bivariate and
      multivariate analyses indicated that the occurrence of >1 CMV episode increased
      the costs of allogeneic HSCT by 25-30% (p < 0.0001). CONCLUSION: Our study, which
      is the largest, single-institution cost study of allogeneic HSCT in Europe, shows
      that two or more CMV episodes significantly increased the transplant cost. New
      prophylactic strategies to prevent CMV infection and disease should decrease
      transplant costs.

PMID- 29207953
TI  - Genomic signature of highland adaptation in fish: a case study in Tibetan
      Schizothoracinae species.
AB  - BACKGROUND: Genome-wide studies on highland adaptation mechanism in terrestrial
      animal have been widely reported with few available for aquatic animals. Tibetan
      Schizothoracinae species are ideal model systems to study speciation and
      adaptation of fish. The Schizothoracine fish, Gymnocypris przewalskii
      ganzihonensis had underwent the ecological niche shift from salt water to
      freshwater, and also experienced a recent split from Gymnocypris przewalskii
      przewalskii. In addition, G. p. ganzihonensis inhabited harsh aquatic environment
      including low temperature and hypoxia as well as other Schizothoracinae species,
      its genetic mechanism of highland adaptation have yet to be determined. RESULTS:
      Our study used comparative genomic analysis based on the transcriptomic data of
      G. p. ganzihonensis and other four fish genome datasets to investigate the
      genetic basis of highland adaptation in Schizothoracine fish. We found that
      Schizothoracine fish lineage on the terminal branch had an elevated dN/dS ratio
      than its ancestral branch. A total of 202 gene ontology (GO) categories involved
      into transport, energy metabolism and immune response had accelerated
      evolutionary rates than zebrafish. Interestingly, we also identified 162 genes
      showing signature of positive selection (PSG) involved into energy metabolism,
      transport and immune response in G. p. ganzihonesis. While, we failed to find any
      PSG related to hypoxia response as previous studies. CONCLUSIONS: Comparative
      genomic analysis based on G. p. ganzihonensis transcriptome data revealed
      significant genomic signature of accelerated evolution ongoing within Tibetan
      Schizothoracinae species lineage. Molecular evolution analysis suggested that
      genes involved in energy metabolism, transport and immune response functions in
      Schizothoracine fish underwent positive selection, especially in innate immunity
      including toll-like receptor signaling pathway genes. Taken together, our result
      as a case study in Schizothoracinae species provides novel insights in
      understanding the aquatic animal adaptation to extreme environment on the Tibetan
      Plateau, and also provides valuable genomic resource for further functional
      verification studies.

PMID- 29207954
TI  - The Turkish validation of the Brief International Cognitive Assessment for
      Multiple Sclerosis (BICAMS) battery.
AB  - BACKGROUND: Cognitive impairment may be seen in as many as 43-70% of patients
      with multiple sclerosis (MS) and may be observed in all MS subtypes. The Brief
      International Cognitive Assessment in Multiple Sclerosis (BICAMS) battery may be
      used to evaluate cognition status. The purpose of the current study is to
      validate the BICAMS battery in Turkish. METHODS: Patients with MS attending our
      clinic between September 2014 and April 2015 were invited to participate. Healthy
      control participants were matched in terms of age, gender and years of education.
      RESULTS: One hundred seventy-three MS patients and 153 healthy control
      participants were enrolled in the study. MS patients performed significantly
      worse in all trials than the members of the healthy control group. In addition,
      cognitive dysfunction was identified in 78 of the 173 (45.1%) patients. In the MS
      with cognitive impairment group, 64 out of 151 (42.4%) subjects were RRMS
      patients, 12 out of 18 (66.7%) were secondary progressive MS patients, and 2 out
      of 4 (50%) were primer progressive MS patients. CONCLUSIONS: The BICAMS has been
      proposed for assessing cognitive impairment in MS patients. This study shows that
      the battery is suitable for use in Turkey.

PMID- 29207955
TI  - Classification schemes for knowledge translation interventions: a practical
      resource for researchers.
AB  - BACKGROUND: As implementation science advances, the number of interventions to
      promote the translation of evidence into healthcare, health systems, or health
      policy is growing. Accordingly, classification schemes for these knowledge
      translation (KT) interventions have emerged. A recent scoping review identified
      51 classification schemes of KT interventions to integrate evidence into
      healthcare practice; however, the review did not evaluate the quality of the
      classification schemes or provide detailed information to assist researchers in
      selecting a scheme for their context and purpose. This study aimed to further
      examine and assess the quality of these classification schemes of KT
      interventions, and provide information to aid researchers when selecting a
      classification scheme. METHODS: We abstracted the following information from each
      of the original 51 classification scheme articles: authors' objectives; purpose
      of the scheme and field of application; socioecologic level (individual,
      organizational, community, system); adaptability (broad versus specific); target
      group (patients, providers, policy-makers), intent (policy, education, practice),
      and purpose (dissemination versus implementation). Two reviewers independently
      evaluated the methodological quality of the development of each classification
      scheme using an adapted version of the AGREE II tool. Based on these assessments,
      two independent reviewers reached consensus about whether to recommend each
      scheme for researcher use, or not. RESULTS: Of the 51 original classification
      schemes, we excluded seven that were not specific classification schemes, not
      accessible or duplicates. Of the remaining 44 classification schemes, nine were
      not recommended. Of the 35 recommended classification schemes, ten focused on
      behaviour change and six focused on population health. Many schemes (n = 29)
      addressed practice considerations. Fewer schemes addressed educational or policy
      objectives. Twenty-five classification schemes had broad applicability, six were
      specific, and four had elements of both. Twenty-three schemes targeted health
      providers, nine targeted both patients and providers and one targeted policy
      makers. Most classification schemes were intended for implementation rather than
      dissemination. CONCLUSIONS: Thirty-five classification schemes of KT
      interventions were developed and reported with sufficient rigour to be
      recommended for use by researchers interested in KT in healthcare. Our additional
      categorization and quality analysis will aid in selecting suitable classification
      schemes for research initiatives in the field of implementation science.

PMID- 29207956
TI  - A microsatellite diversity analysis and the development of core-set germplasm in
      a large hulless barley (Hordeum vulgare L.) collection.
AB  - BACKGROUND: Clarifying genetic diversity in a large germplasm resource plays
      important roles in experimental designs that provides flexible utility in
      fundamental research and breeding in crops. However, the work is limited due to
      small collections of barley that are insufficient representatives. RESULTS: In
      the present study, we collected 562 hulless barley (Hordeum vulgare L.)
      accessions with worldwide geographic origins and evaluated their genetic
      variability and relatedness based on 93 simple sequence repeat (SSR) markers. In
      an integrated analysis of the population structure, analysis of molecular
      variance (AMOVA) and pairwise F ST, the 562 barley accessions exhibited a strong
      stratification that allowed for them to be divided into two major subpopulations
      (p1 and p2) and an admixture subpopulation, with 93, 408 and 61 accessions,
      respectively. In a neutral test, considerable proportions of SSR alleles
      expressed the strong non-neutrality in specific subpopulations (44 and 37), which
      are probably responsible for population differentiation. To reduce the diversity
      redundancy in large barley collections, we delicately selected a core set of 200
      barley accessions as a tradeoff between diversity and representativeness in an
      easily handled population. In comparing the 562 barley accessions, the core
      barley set accounted for 96.2% of allelic diversity and 93% to 95% of phenotypic
      variability, whereas it exhibited a significant enhancement in minor allelic
      frequencies, which probably benefit association mapping in the barley core set.
      CONCLUSIONS: The results provided additional insight into the genetic structure
      in a large barley germplasm resource, from which an easily manageable barley core
      set was identified, demonstrating the great potential for discovering key QTLs
      and ultimately facilitating barley breeding progress.

PMID- 29207957
TI  - Placenta response of inflammation and oxidative stress in low-risk term
      childbirth: the implication of delivery mode.
AB  - BACKGROUND: Caesarean delivery rate is increasing gradually in China and there is
      no doubt that delivery mode is closely associated with the maternal health and
      infant development.This study examined the independent effect of delivery mode on
      placenta inflammation response and oxidative stress response. METHODS: A total of
      3474 pregnant women recruited in Ma'anshan Birth Cohort Study were the initial
      study population. Data on maternal socio-demographic characteristics and pre
      pregnancy BMI were collected at their 1st antenatal checkups. Pregnancy-specific
      anxiety was assessed during the three trimesters of pregnancy. Common pregnant
      complications were monitored in the whole pregnancy period. Delivery modes, as
      well as newborn characteristics were abstracted from medical records. Delivery
      modes included vaginal deliveries (VD), caesarean delivery with medical
      indications (CDMI), caesarean delivery on maternal request (CDMR) and urgent
      cesarean delivery (UCD). Placentas were collected during childbirth. The mRNA
      expression of IL-1beta, TNF-a, IL-6, IFN-gamma, IL-4, IL-10, IL-8, and HO-1 were
      assessed in the final sample of 1978 low-risk women with singleton term-births.
      RESULTS: The overall rate of caesarean delivery (CD) was 50.5% (1650/3265) in
      singleton term childbirths in this study. Among women who reported definite CD
      reasons, 56.8%of them chose the surgery without any medical indications.It shows
      a non-linear relationship between cytokines related with placenta inflammatory
      response, oxidative stress response and different delivery modes. At high
      percentiles of IL-1beta, IFN-gamma and IL-8, women with CDMR had higher
      expression levels compared to women with VD. Women with CDMI had higher levels at
      median percentiles of IL-1beta, IFN-gamma and IL-8. Women with CDMR had higher
      expression compared with VD at high percentiles of IL-6 and HO-1, and women with
      CDMI had higher levels of these two cytokines at their low percentiles. It is
      worth noting that at high percentiles, compared with normal delivery, the
      expression of IL-1beta, IFN-gamma, IL-8 and HO-1 have significantly altered in
      women with CDMR. CONCLUSION: A high overall CD rate was found in this study, and
      caesarean delivery on maternal request was the major contributor to the high
      prevalence. Maternal placental oxidative stress and inflammatory response were
      closely associated with delivery mode. The effect is much amplified at high
      levels of expression in women who chose CD on maternal request.Such difference
      needs to be noticed and may have important implications for obstetricians,
      midwives and other perinatal health care workers.

PMID- 29207958
TI  - Bloodstream infections at a tertiary level paediatric hospital in South Africa.
AB  - BACKGROUND: Bloodstream infection (BSI) in children causes significant morbidity
      and mortality. There are few studies describing the epidemiology of BSI in South
      African children. METHODS: A retrospective descriptive cohort study was conducted
      at a paediatric referral hospital in Cape Town, South Africa. The National Health
      Laboratory Service (NHLS) microbiology database was accessed to identify positive
      blood culture specimens during the period 2011-2012. Demographic and clinical
      details, antimicrobial management and patient outcome information were extracted
      from medical and laboratory records. Antibiotic susceptibility results of
      identified organisms were obtained from the NHLS database. RESULTS: Of the 693
      unique bacterial and fungal BSI episodes identified during the study period, 248
      (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74
      (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per
      1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus
      pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae,
      Acinetobacter baumanii and S.aureus were most commonly isolated in HA-BSI. On
      multivariable analysis, severe underweight, severe anaemia at the time of BSI,
      admission in the ICU at the time of BSI, and requiring ICU admission after BSI
      was diagnosed were significantly associated with 14-day mortality. CONCLUSION:
      This study adds to the limited literature describing BSI in children in Africa.
      Further studies are required to understand the impact that BSI has on the
      paediatric population in sub-Saharan Africa.

PMID- 29207959
TI  - Insulin-like growth factor receptor and sphingosine kinase are prognostic and
      therapeutic targets in breast cancer.
AB  - BACKGROUND: Targeting the type 1 insulin-like growth factor receptor (IGF1R) in
      breast cancer remains an ongoing clinical challenge. Oncogenic IGF1R-signaling
      occurs via activation of PI3K/AKT/MAPK downstream mediators which regulate cell
      proliferation and protein synthesis. To further understand IGF1R signaling we
      have investigated the involvement of the oncogenic IGF1R-related sphingosine
      kinase (SphK) pathway. METHODS: The prognostic (overall survival, OS) and
      therapeutic (anti-endocrine therapy) co-contribution of IGF1R and SphK1 were
      investigated using breast cancer patient samples (n = 236) for
      immunohistochemistry to measure total and phosphorylated IGF1R and SphK1. Kaplan
      Meier and correlation analyses were performed to determine the contribution of
      high versus low IGF1R and/or SphK1 expression to OS in patients treated with anti
      endocrine therapy. Cell viability and colony formation in vitro studies were
      completed using estrogen receptor (ER) positive and negative breast cancer cell
      lines to determine the benefit of IGF1R inhibitor (OSI-906) and SphK inhibitor
      (SKI-II) co-therapy. Repeated measures and 1-way ANOVA were performed to compare
      drug treatments groups and the Chou-Talalay combination index (CI) was calculated
      to estimate drug synergism in vitro (CI < 1). RESULTS: High IGF1R and SphK1
      protein co-expression in tumor tissue was associated with improved OS
      specifically in ER-positive disease and stratified for anti-endocrine therapy. A
      significant synergistic inhibition of cell viability and/or colony formation
      following OSI-906 and SKI-II co-treatment in vitro was evident (p < 0.05, CI <
      1). CONCLUSION: We conclude that high IGF1R and SphK1 co-expression act together
      as prognostic indicators and are potentially, dual therapeutic targets for the
      development of a more effective IGF1R-directed combination breast cancer therapy.

PMID- 29207960
TI  - Decreased expression of the beta2 integrin on tumor cells is associated with a
      reduction in liver metastasis of colorectal cancer in mice.
AB  - BACKGROUND: Lymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one
      of the main adhesion molecules used by immune cells to infiltrate the liver under
      inflammatory conditions. Recently, the expression of this integrin has also been
      reported on several solid tumors, including colorectal cancer. However, its
      functional role in the metastatic progression to the liver remains unknown. Using
      in vitro assays and an experimental orthotopic in vivo model of liver metastasis,
      we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by
      means of the partial depletion of the beta2 subunit of LFA-1, required for
      integrin activation, firm adhesion and signaling. METHODS: To do so, we evaluated
      the effects of beta2 reduction on the murine colon carcinoma C26 cell line on
      their pro-metastatic features in vitro and their metastatic potential in vivo in
      a mouse model of colon carcinoma metastasis to the liver. RESULTS: The reduction
      in beta2 integrin expression correlated with a slower proliferation, and a
      reduced adhesion and migration of C26 cells in an in vitro setting. Additionally,
      tumor cells with a reduced in beta2 integrin expression were unable to activate
      the liver sinusoidal endothelial cells (LSECs). This resulted in a recovery of
      the cytotoxic potential of liver lymphocytes which is compromised by LSECs
      activated by C26 cells. This was related to the abrogation of RNA expression of
      inflammatory and angiogenic cytokines by C26 cells after their activation with
      sICAM-1, the main ligand of beta2alphaL. Furthermore, in vivo tumor cell
      retention and metastasis were profoundly reduced, along with a decrease in the
      recruitment and infiltration of myeloid derived suppressor cells (MDSCs) and
      lymphocytes to the liver. CONCLUSION: Taken together, our findings uncovered the
      modulatory role for the tumor beta2 subunit of the LFA-1 integrin in the
      metastatic progression of colorectal cancer to the liver by impairing activation
      of liver endothelium and thus, the local immune response in the liver. Besides,
      this integrin also showed to be critical in vivo for tumor cell retention,
      cytokine release, leukocyte recruitment and metastasis development. These data
      support a therapeutical potential of the integrin LFA-1 as a target for the
      treatment of colorectal liver metastasis.

PMID- 29207961
TI  - When and how should multiple imputation be used for handling missing data in
      randomised clinical trials - a practical guide with flowcharts.
AB  - BACKGROUND: Missing data may seriously compromise inferences from randomised
      clinical trials, especially if missing data are not handled appropriately. The
      potential bias due to missing data depends on the mechanism causing the data to
      be missing, and the analytical methods applied to amend the missingness.
      Therefore, the analysis of trial data with missing values requires careful
      planning and attention. METHODS: The authors had several meetings and discussions
      considering optimal ways of handling missing data to minimise the bias potential.
      We also searched PubMed (key words: missing data; randomi*; statistical analysis)
      and reference lists of known studies for papers (theoretical papers; empirical
      studies; simulation studies; etc.) on how to deal with missing data when
      analysing randomised clinical trials. RESULTS: Handling missing data is an
      important, yet difficult and complex task when analysing results of randomised
      clinical trials. We consider how to optimise the handling of missing data during
      the planning stage of a randomised clinical trial and recommend analytical
      approaches which may prevent bias caused by unavoidable missing data. We consider
      the strengths and limitations of using of best-worst and worst-best sensitivity
      analyses, multiple imputation, and full information maximum likelihood. We also
      present practical flowcharts on how to deal with missing data and an overview of
      the steps that always need to be considered during the analysis stage of a trial.
      CONCLUSIONS: We present a practical guide and flowcharts describing when and how
      multiple imputation should be used to handle missing data in randomised clinical.

PMID- 29207963
TI  - Two staging systems for gastrointestinal stromal tumors in the stomach: which is
      better?
AB  - BACKGROUND: The prognosis of a gastrointestinal stromal tumor (GIST) is
      influenced by its anatomic site; however, few studies on the prognosis of gastric
      GISTs have been reported. The aims of this study were to evaluate long-term
      prognoses of patients who underwent surgical resection for gastric GISTs and to
      compare the clinical efficacy of two staging systems: the National Institutes of
      Health (NIH) consensus criteria and the 7th Union for International Cancer
      Control/American Joint Committee on Cancer (UICC/AJCC) tumor-node-metastasis
      (TNM) staging system. METHODS: We conducted a retrospective observational study
      of 145 patients who underwent surgical resection for gastric GISTs between
      February 2001 and June 2012 at Pusan National University Hospital (Busan, Korea).
      Recurrence and 5-year recurrence-free survival (RFS) rates were analyzed.
      RESULTS: During a median follow-up period of 44 months (range, 6-144 months), 11
      recurrent lesions were detected in 9 patients (6.4%). On multivariate analysis,
      tumor size (>5 cm), mitotic count (>5/50 high-power fields), and epithelioid and
      mixed pathological type were significantly associated with recurrence. The
      overall 5-year RFS rate was 93.4%. Although no statistically significant
      differences were detected (C-statistic difference P = 0.886), all metrics showed
      lower values for the UICC/AJCC TNM staging system than for the NIH consensus
      criteria, suggesting that the UICC/AJCC TNM staging system may be a better model.
      CONCLUSIONS: The 5-year RFS rate in patients who underwent curative resection for
      gastric GISTs was excellent. The UICC/AJCC TNM staging system may be more useful
      than the NIH consensus criteria for risk categorization of patients with gastric
      GISTs.

PMID- 29207962
TI  - A partially supervised physical activity program for adult and adolescent
      survivors of childhood cancer (SURfit): study design of a randomized controlled
      trial [NCT02730767].
AB  - BACKGROUND: Beyond survival of nowadays >80%, modern childhood cancer treatment
      strives to preserve long-term health and quality of life. However, the majority
      of today's survivors suffer from short- and long-term adverse effects such as
      cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue,
      depression, and reduced physical fitness and quality of life. Regular exercise
      can play a major role to mitigate or prevent such late-effects. Despite this,
      there are no data on the effects of regular exercise in childhood cancer
      survivors from randomized controlled trials (RCTs). Primary outcome of the
      current RCT is therefore the effect of a 12-months exercise program on a
      composite cardiovascular disease risk score in childhood cancer survivors.
      Secondary outcomes are single cardiovascular disease risk factors, glycaemic
      control, bone health, body composition, physical fitness, physical activity,
      quality of life, mental health, fatigue and adverse events (safety). METHODS: A
      total of 150 childhood cancer survivors aged >=16 years and diagnosed >=5 years
      prior to the study are recruited from Swiss paediatric oncology clinics.
      Following the baseline assessments patients are randomized 1:1 into an
      intervention and control group. Thereafter, they are seen at month 3, 6 and 12
      for follow-up assessments. The intervention group is asked to add >=2.5 h of
      intense physical activity/week, including 30 min of strength building and 2 h of
      aerobic exercises. In addition, they are told to reduce screen time by 25%.
      Regular consulting by physiotherapists, individual web-based activity diaries,
      and pedometer devices are used as motivational tools for the intervention group.
      The control group is asked to keep their physical activity levels constant.
      DISCUSSION: The results of this study will show whether a partially supervised
      exercise intervention can improve cardiovascular disease risk factors, bone
      health, body composition, physical activity and fitness, fatigue, mental health
      and quality of life in childhood cancer survivors. If the program will be
      effective, all relevant information of the SURfit physical activity intervention
      will be made available to interested clinics that treat and follow-up childhood
      cancer patients to promote exercise in their patients. TRIAL REGISTRATION:
      Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration
      date: 10.12.2015.

PMID- 29207964
TI  - Concordance of FDG PET/CT metabolic tumour volume versus DW-MRI functional tumour
      volume with T2-weighted anatomical tumour volume in cervical cancer.
AB  - BACKGROUND: 18F-fluoro-deoxyglucose positron emission tomography with computed
      tomography (FDG PET/CT) has been employed to define radiotherapy targets using a
      threshold based on the standardised uptake value (SUV), and has been described
      for use in cervical cancer. The aim of this study was to evaluate the concordance
      between the metabolic tumour volume (MTV) measured on FDG PET/CT and the
      anatomical tumour volume (ATV) measured on T2-weighted magnetic resonance imaging
      (T2W-MRI); and compared with the functional tumour volume (FTV) measured on
      diffusion-weighted MRI (DW-MRI) in cervical cancer, taking the T2W-ATV as gold
      standard. METHODS: Consecutive newly diagnosed cervical cancer patients who
      underwent FDG PET/CT and DW-MRI were retrospectively reviewed from June 2013 to
      July 2017. Volumes of interest was inserted to the focal hypermetabolic activity
      corresponding to the cervical tumour on FDG PET/CT with automated tumour
      contouring and manual adjustment, based on SUV 20%-80% thresholds of the maximum
      SUV (SUVmax) to define the MTV20-80, with intervals of 5%. Tumour areas were
      manually delineated on T2W-MRI and multiplied by slice thickness to calculate the
      ATV. FTV were derived by manually delineating tumour area on ADC map, multiplied
      by the slice thickness to determine the FTV(manual). Diffusion restricted areas
      was extracted from b0 and ADC map using K-means clustering to determine the
      FTV(semi-automated). The ATVs, FTVs and the MTVs at different thresholds were
      compared using the mean and correlated using Pearson's product-moment
      correlation. RESULTS: Twenty-nine patients were evaluated (median age 52 years).
      Paired difference of mean between ATV and MTV was the closest and not
      statistically significant at MTV30 (-2.9cm3, -5.2%, p = 0.301). This was less
      than the differences between ATV and FTV(semi-automated) (25.0cm3, 45.1%, p <
      0.001) and FTV(manual) (11.2cm3, 20.1%, p = 0.001). The correlation of MTV30 with
      ATV was excellent (r = 0.968, p < 0.001) and better than that of the FTVs.
      CONCLUSIONS: Our study demonstrated that MTV30 was the only parameter
      investigated with no statistically significant difference with ATV, had the least
      absolute difference from ATV, and showed excellent positive correlation with ATV,
      suggesting its superiority as a functional imaging modality when compared with DW
      MRI and supporting its use as a surrogate for ATV for radiotherapy tumour
      contouring.

PMID- 29207965
TI  - Long-term intra-individual variability of albuminuria in type 2 diabetes
      mellitus: implications for categorization of albumin excretion rate.
AB  - BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage renal
      disease in the Western world. Early and accurate identification of DKD offers the
      best chance of slowing the progression of kidney disease. An important method for
      evaluating risk of progressive DKD is abnormal albumin excretion rate (AER). Due
      to the high variability in AER, most guidelines recommend the use of more than or
      equal to two out of three AER measurements within a 3- to 6-month period to
      categorise AER. There are recognised limitations of using AER as a marker of DKD
      because one quarter of patients with type 2 diabetes may develop kidney disease
      without an increase in albuminuria and spontaneous regression of albuminuria
      occurs frequently. Nevertheless, it is important to investigate the long-term
      intra-individual variability of AER in participants with type 2 diabetes.
      METHODS: Consecutive AER measurements (median 19 per subject) were performed in
      497 participants with type 2 diabetes from 1999 to 2012 (mean follow-up 7.9 +/- 3
      years). Baseline clinical characteristics were collected to determine
      associations with AER variability. Participants were categorised as having normo
      , micro- or macroalbuminuria according to their initial three AER measurements.
      Participants were then categorised into four patterns of AER trajectories:
      persistent, intermittent, progressing and regressing. Coefficients of variation
      were used to measure intra-individual AER variability. RESULTS: The median
      coefficient of variation of AER was 53.3%, 76.0% and 67.0% for subjects with
      normo-, micro- or macroalbuminuria at baseline. The coefficient of variation of
      AER was 37.7%, 66% and 94.8% for subjects with persistent, intermittent and
      progressing normoalbuminuria; 43%, 70.6%, 86.1% and 82.3% for subjects with
      persistent, intermittent, progressing and regressing microalbuminuria; and 55.2%,
      67% and 82.4% for subjects with persistent, intermittent and regressing
      macroalbuminuria, respectively. CONCLUSION: High long-term variability of AER
      suggests that two out of three AER measurements may not always be adequate for
      the optimal categorisation and prediction of AER.

PMID- 29207966
TI  - Study protocol for a cluster-randomized trial to compare human papillomavirus
      based cervical cancer screening in community-health campaigns versus health
      facilities in western Kenya.
AB  - BACKGROUND: Despite guidelines for cervical cancer prevention in low-resource
      countries, a very small proportion of women in these settings undergo screening,
      and even fewer women are successfully treated. Using pilot data from western
      Kenya and World Health Organization recommendations, we developed a protocol to
      implement evidence-based cervical cancer screening and linkage to treatment
      strategies to the rural communities. We describe the protocol for a cluster
      randomized trial to compare two implementation strategies for human
      papillomavirus (HPV)-based cervical cancer screening program using metrics
      described in the RE-AIM (reach, efficacy, adaption, implementation and
      maintenance) framework. METHODS: The study is a three-year, two-phase cluster
      randomized trial in 18 communities in western Kenya. During Phase 1, six control
      communities were offered screening in health facilities; and six intervention
      communities were offered screening in community health campaigns. Screening was
      done with human-papillomavirus testing through self-collected specimens. Phase 1
      ended and we are working in partnership with communities to further contextualize
      the implementation strategy for screening, and develop an enhanced linkage to
      treatment plan. This plan will be tested in an additional six communities in
      Phase 2 (enhanced intervention). We will compare the reach, efficacy, cost
      effectiveness and adaptability of the implementation strategies. DISCUSSION:
      Effective low-cost cervical cancer prevention technologies are becoming more
      widely available in low- and middle-income countries. Despite increasing
      government support for cervical cancer prevention, there remains a sizeable gap
      in service availability. We will use implementation science to identify the most
      effective strategies to fill this gap through development of context-specific
      evidence-based solutions. This protocol design and results can help guide
      implementation of cervical cancer screening in similar settings, where women are
      most underserved and at highest risk for disease. TRIAL REGISTRATION: This trial
      is registered at ClinicalTrials.gov , NCT02124252 .

PMID- 29207967
TI  - Identification by mass spectrometry and automated susceptibility testing from
      positive bottles: a simple, rapid, and standardized approach to reduce the
      turnaround time in the management of blood cultures.
AB  - BACKGROUND: Speeding up identification and antimicrobial susceptibility testing
      (AST) is of foremost importance in the management of blood cultures. Here, we
      describe a simple, rapid, and standardized approach based on a very short-term
      incubation on solid medium from positive blood cultures followed by MALDI-TOF
      mass spectrometry identification and automated AST. The aim of the study was to
      evaluate the impact in the laboratory practice of this new procedure with respect
      to that previously used (standard method) by comparing TAT and cumulative
      percentage of final reports to clinicians. RESULTS: Compared with the standard
      method, the new procedure gave correct organism identification at genus or
      species level in 98.4% of monomicrobial samples. AST resulted in 97.7% essential
      agreement and 98.1% categorical agreement, with 0.9% minor errors, 1.0% major
      error, and 1.5% very major errors. The mean turnaround time to identification and
      AST was 61.4 h by using the new method compared to 83.1 h by using standard
      procedure. Concerning cumulative percentages of final reports, approximately a
      third of results were available at 48 h from the check-in of the sample when
      using the new procedure, whereas no final reports were ready at the same time
      with the standard method. CONCLUSIONS: The new procedure allows faster and
      reliable results using a simple and standardized approach. Thus, it represents an
      important tool for a more rapid management of blood cultures when molecular
      methods are not available in the laboratory.

PMID- 29207968
TI  - Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort
      analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older
      patient.
AB  - BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these
      are underrepresented in the phase III clinical studies that established the
      current treatment standards. This leads to uncertainty regarding the treatment of
      older patients with potentially toxic but active regimens like FOLFIRINOX.
      METHODS: We conducted a retrospective analysis of patients treated according to
      the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on
      older patients. RESULTS: Overall survival in our cohort was 10.2 months. Only 43%
      of patients did not need dose adaptations, but dose reductions did not lead to an
      inferior survival. We did not find evidence that patients aged 65 years and older
      deemed fit enough for palliative treatment had more toxicities or a worse outcome
      than younger patients. CONCLUSION: We conclude that treatment with the FOLFIRINOX
      protocol in patients with pancreatic cancer should not be withhold from patients
      solely based on their chronological age but rather be based on the patient's
      performance status and comorbidities.

PMID- 29207969
TI  - Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral
      aetiology - a prospective study.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma
      (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is
      not clear. METHODS: Patients with nvHCC, referred to a Hepatobiliary Clinic from
      September 2011-2015 were screened. HCC was diagnosed using American Association
      for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed
      when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for
      End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated
      against patient characteristics, tumour characteristics and survival. RESULTS:
      Three hundred eighty-nine patients with nvHCC [age 64(12-88) years; 344(88.4%)
      males] were screened. Median AFP was 25.46 ng/ml (1.16-100,000). 41.2% (n = 160)
      Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female
      gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05),
      late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels.
      Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage
      tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was
      associated with longer survival (16 vs. 7 months, P < 0.001). CONCLUSION: Pre
      treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over
      400 ng/ml was associated with aggressive tumour behaviour and poor prognosis.

PMID- 29207970
TI  - Overexpression of Cullin7 is associated with hepatocellular carcinoma progression
      and pathogenesis.
AB  - BACKGROUND: Overexpression of Cullin7 is associated with some types of
      malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains
      unclear. The aim of this study was to investigate the role of Cullin7 in
      pathogenesis and the progression of hepatocellular carcinoma. METHODS: In the
      present study, the expression of Cullin7 in hepatocellular carcinoma cell lines
      and five surgical hepatocellular carcinoma specimens was detected with
      quantitative reverse transcription PCR and western blotting. In addition, the
      protein expression of Cullin7 was examined in 162 cases of archived
      hepatocellular carcinoma using immunohistochemistry. RESULTS: We found elevated
      expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma
      cell lines, and Cullin7 protein was significantly upregulated in hepatocellular
      carcinoma compared with paired normal hepatic tissues. The immunohistochemistry
      analysis revealed that overexpression of Cullin7 occurred in 69.1% of
      hepatocellular carcinoma samples, which was a significantly higher rate than that
      in adjacent normal hepatic tissue (P < 0.01). Statistical analysis found that
      overexpression of Cullin7 was significantly associated with lymph node
      metastasis, tumor thrombus of the portal vein and advanced clinical stage (P <
      0.05). Furthermore, by overexpressing Cullin7 in hepatocellular carcinoma HepG2
      cells, we revealed that Cullin7 could significantly enhance cell proliferation,
      growth, migration and invasion. Conversely, knocking down Cullin7 expression with
      short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell
      proliferation, growth, migration and invasion. CONCLUSION: Our studies provide
      evidence that overexpression of Cullin7 plays an important role in the
      pathogenesis and progression of hepatocellular carcinoma and may be a valuable
      marker for hepatocellular carcinoma management.

PMID- 29207972
TI  - Disparities in the regional, hospital and individual levels of antibiotic use in
      gallstone surgery in Sweden.
AB  - BACKGROUND: Antimicrobial resistance may be promoted by divergent routines and
      lack of conformity in antibiotic treatment, especially regarding the practice of
      antibiotic prophylaxis. The aim of the present study was to assess differences in
      gallstone surgery regarding antibiotic use in Sweden. METHODS: The study was
      based on data from the Swedish Register for Gallstone Surgery and ERCP (GallRiks)
      2005-2015. Funnel plots were used to test impact of grouping factors, including,
      hospital and surgeon and to identify units that deviated from the rest of the
      population. RESULTS: After adjusting for cofounders including age, gender, ASA
      classification, indication for surgery, operation time, gallbladder perforation
      and emergency status, there were 0/21 (0%) at the regional level, 18/76 (24%) at
      the hospital level and 128/1038 (12%) at the surgeon level outside the 99.9%
      confidence interval (CI). The estimated median odds ratios were 1.13 (95% CI 1.00
      1.31) at the regional level, 1.93 (95% CI 1.70-2.19) at the hospital level and
      2.38 (95% CI 2.26-2.50) at the surgeon level. CONCLUSION: There are significant
      differences between hospitals and surgeons, but little or no differences between
      regions. These deviations confirm the lack of standardization in regards to
      prescription of antibiotic prophylaxis and the need more uniform routines
      regarding antibiotic usage. Randomized controlled trials and large population
      based studies are necessary to assess assessing the effectiveness and safety of
      antibiotic prophylaxis in gallstone surgery.

PMID- 29207971
TI  - Comparison of the association of mammographic density and clinical factors with
      ductal carcinoma in situ versus invasive ductal breast cancer in Korean women.
AB  - BACKGROUND: In spite of the increasing incidence of in situ breast cancer, the
      information about the risk factors of in situ breast cancer (DCIS) is scarce as
      compared to the information available for invasive ductal breast cancer (IDC),
      with inconsistent findings regarding the difference in risk factors between DCIS
      and IDC. METHODS: We enrolled 472 women with IDC and 90 women with DCIS and 1088
      controls matching for age and menopausal status. Information on risk factors was
      collected through self-administered questionnaire. Percent mammographic dense
      area (PDA), absolute mammographic dense area (ADA), and nondense area were
      assessed using a computer-assisted thresholding technique. Odds ratio (OR) and
      95% confidence intervals (CI) were estimated by conditional logistic regression
      model with adjustment for covariates. RESULTS: Later age at menarche and regular
      physical exercise were associated with decreased risk of IDC, whereas alcohol
      consumption, previous benign breast disease, and family history of breast cancer
      were associated with increased risk of IDC. For DCIS, previous benign breast
      disease and alcohol consumption were associated with the increased risk, and
      regular physical exercise was associated with decreased risk. Increase of ADA by
      1-quartile level and PDA increase by 10% were associated with 1.10 (95% CI: 1.01,
      1.21) and 1.10 (95% CI: 1.01, 1.19) times greater risk of IDC, respectively. The
      increase of ADA by 1-quartile level and PDA increase by 10% were associated with
      1.17 (95% CI: 0.91, 1.50) times and 1.11 (95% CI:0.90,1.37) times greater risk of
      DCIS, respectively, but the associations were not statistically significant.
      There was no significant difference in the association with risk factors and
      mammographic density measures between IDC and DCIS (P > 0.1). CONCLUSIONS:
      Differential associations of DCIS with mammographic density and risk factors as
      compared with the associations of IDC were not evident. This finding suggests
      that IDC and DCIS develop through the shared causal pathways.

PMID- 29207973
TI  - Identifying models of HIV care and treatment service delivery in Tanzania,
      Uganda, and Zambia using cluster analysis and Delphi survey.
AB  - BACKGROUND: Organization of HIV care and treatment services, including clinic
      staffing and services, may shape clinical and financial outcomes, yet there has
      been little attempt to describe different models of HIV care in sub-Saharan
      Africa (SSA). Information about the relative benefits and drawbacks of different
      models could inform the scale-up of antiretroviral therapy (ART) and associated
      services in resource-limited settings (RLS), especially in light of expanded
      client populations with country adoption of WHO's test and treat recommendation.
      METHODS: We characterized task-shifting/task-sharing practices in 19 diverse ART
      clinics in Tanzania, Uganda, and Zambia and used cluster analysis to identify
      unique models of service provision. We ran descriptive statistics to explore how
      the clusters varied by environmental factors and programmatic characteristics.
      Finally, we employed the Delphi Method to make systematic use of expert opinions
      to ensure that the cluster variables were meaningful in the context of actual
      task-shifting of ART services in SSA. RESULTS: The cluster analysis identified
      three task-shifting/task-sharing models. The main differences across models were
      the availability of medical doctors, the scope of clinical responsibility
      assigned to nurses, and the use of lay health care workers. Patterns of
      healthcare staffing in HIV service delivery were associated with different
      environmental factors (e.g., health facility levels, urban vs. rural settings)
      and programme characteristics (e.g., community ART distribution or integrated
      tuberculosis treatment on-site). CONCLUSIONS: Understanding the relative
      advantages and disadvantages of different models of care can help national
      programmes adapt to increased client load, select optimal adherence strategies
      within decentralized models of care, and identify differentiated models of care
      for clients to meet the growing needs of long-term ART patients who require more
      complicated treatment management.

PMID- 29207974
TI  - Spectrum of mutations in monogenic diabetes genes identified from high-throughput
      DNA sequencing of 6888 individuals.
AB  - BACKGROUND: Diagnosis of monogenic as well as atypical forms of diabetes mellitus
      has important clinical implications for their specific diagnosis, prognosis, and
      targeted treatment. Single gene mutations that affect beta-cell function
      represent 1-2% of all cases of diabetes. However, phenotypic heterogeneity and
      lack of family history of diabetes can limit the diagnosis of monogenic forms of
      diabetes. Next-generation sequencing technologies provide an excellent
      opportunity to screen large numbers of individuals with a diagnosis of diabetes
      for mutations in disease-associated genes. METHODS: We utilized a targeted
      sequencing approach using the Illumina HiSeq to perform a case-control sequencing
      study of 22 monogenic diabetes genes in 4016 individuals with type 2 diabetes
      (including 1346 individuals diagnosed before the age of 40 years) and 2872
      controls. We analyzed protein-coding variants identified from the sequence data
      and compared the frequencies of pathogenic variants (protein-truncating variants
      and missense variants) between the cases and controls. RESULTS: A total of 40
      individuals with diabetes (1.8% of early onset sub-group and 0.6% of adult onset
      sub-group) were carriers of known pathogenic missense variants in the GCK, HNF1A,
      HNF4A, ABCC8, and INS genes. In addition, heterozygous protein truncating
      mutations were detected in the GCK, HNF1A, and HNF1B genes in seven individuals
      with diabetes. Rare missense mutations in the GCK gene were significantly over
      represented in individuals with diabetes (0.5% carrier frequency) compared to
      controls (0.035%). One individual with early onset diabetes was homozygous for a
      rare pathogenic missense variant in the WFS1 gene but did not have the additional
      phenotypes associated with Wolfram syndrome. CONCLUSION: Targeted sequencing of
      genes linked with monogenic diabetes can identify disease-relevant mutations in
      individuals diagnosed with type 2 diabetes not suspected of having monogenic
      forms of the disease. Our data suggests that GCK-MODY frequently masquerades as
      classical type 2 diabetes. The results confirm that MODY is under-diagnosed,
      particularly in individuals presenting with early onset diabetes and clinically
      labeled as type 2 diabetes; thus, sequencing of all monogenic diabetes genes
      should be routinely considered in such individuals. Genetic information can
      provide a specific diagnosis, inform disease prognosis and may help to better
      stratify treatment plans.

PMID- 29207976
TI  - Demographic differences in and correlates of perceived body image discrepancy
      among urban adolescent girls: a cross-sectional study.
AB  - BACKGROUND: Understanding factors related to girls' body image discrepancy, which
      is the difference between self-perceived current or actual and ideal body size,
      is important for addressing body-related issues and preventing adverse sequelae.
      Two aims were to: 1) examine demographic differences in body image discrepancy;
      and 2) determine the association of body image discrepancy with weight status,
      percent body fat, physical activity, sedentary behavior, and cardiovascular (CV)
      fitness among young adolescent girls. METHODS: The cross-sectional study included
      a secondary analysis of baseline data from a group randomized controlled trial
      including 1519 5th-8th grade girls in 24 U.S. schools. Girls completed physical
      activity and sedentary behavior surveys. To indicate perceived current/actual and
      ideal body image, girls selected from nine body figures the one that represented
      how they look now and another showing how they want to look. Girls wore
      accelerometers measuring physical activity. Height, weight, and percent body fat
      were assessed. The Progressive Aerobic CV Endurance Run was used to estimate CV
      fitness. Independent t-test, one- and two-way ANOVA, correlational analyses, and
      hierarchical linear regressions were performed. RESULTS: The majority (67.5%; n =
      1023) chose a smaller ideal than current/actual figure. White girls had higher
      body image discrepancy than Black girls (p = .035). Body image discrepancy
      increased with increasing weight status (F3,1506 = 171.32, p < .001). Moderate-to
      vigorous physical activity (MVPA) and vigorous physical activity were negatively
      correlated with body image discrepancy (r = -.10, p < .001; r = -.14, p < .001,
      respectively), but correlations were not significant after adjusting for race and
      body mass index (BMI), respectively. Body image discrepancy was moderately
      correlated with CV fitness (r = -.55, p < .001). After adjusting for
      demographics, percent body fat, but not CV fitness or MVPA, influenced body image
      discrepancy. Girls with higher percent body fat had higher body image discrepancy
      (p < .001). CONCLUSION: This study provided important information to guide
      interventions for promoting a positive body image among girls. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier NCT01503333 , registration date:
      January 4, 2012.

PMID- 29207975
TI  - Radiomics based analysis to predict local control and survival in hepatocellular
      carcinoma patients treated with volumetric modulated arc therapy.
AB  - BACKGROUND: To appraise the ability of a radiomics based analysis to predict
      local response and overall survival for patients with hepatocellular carcinoma.
      METHODS: A set of 138 consecutive patients (112 males and 26 females, median age
      66 years) presented with Barcelona Clinic Liver Cancer (BCLC) stage A to C were
      retrospectively studied. For a subset of these patients (106) complete
      information about treatment outcome, namely local control, was available.
      Radiomic features were computed for the clinical target volume. A total of 35
      features were extracted and analyzed. Univariate analysis was used to identify
      clinical and radiomics significant features. Multivariate models by Cox
      regression hazards model were built for local control and survival outcome.
      Models were evaluated by area under the curve (AUC) of receiver operating
      characteristic (ROC) curve. For the LC analysis, two models selecting two groups
      of uncorrelated features were analyzes while one single model was built for the
      OS analysis. RESULTS: The univariate analysis lead to the identification of 15
      significant radiomics features but the analysis of cross correlation showed
      several cross related covariates. The un-correlated variables were used to build
      two separate models; both resulted into a single significant radiomic covariate:
      model-1: energy p < 0.05, AUC of ROC 0.6659, C.I.: 0.5585-0.7732; model-2: GLNU p
      < 0.05, AUC 0.6396, C.I.:0.5266-0.7526. The univariate analysis for covariates
      significant with respect to local control resulted in 9 clinical and 13 radiomics
      features with multiple and complex cross-correlations. After elastic net
      regularization, the most significant covariates were compacity and BCLC stage,
      with only compacity significant to Cox model fitting (Cox model likelihood ratio
      test p < 0.0001, compacity p < 0.00001; AUC of the model is 0.8014 (C.I. = 0.7232
      0.8797)). CONCLUSION: A robust radiomic signature, made by one single feature was
      finally identified. A validation phases, based on independent set of patients is
      scheduled to be performed to confirm the results.

PMID- 29207977
TI  - Acute Zonal Occult Outer Retinopathy (AZOOR): a case report of vision improvement
      after intravitreal injection of Ozurdex.
AB  - BACKGROUND: AZOOR was first described by Gass in 1993 as a syndrome with rapid
      loss of one or more extensive zones of the outer retinal segments. It is
      characterized by photopsia, minimal funduscopic changes, and electroretinographic
      abnormalities. The efficacy of systemic steroids in treating AZOOR has been
      previously described and advocated by the concept of autoimmune retinopathy.
      However, the use of intravitreal of sustained-released steroid had not been
      mentioned to date. CASE PRESENTATION: A 34-year-old man had sudden onset of
      central scotoma and photopsia in the left eye. His visual acuity continued
      deteriorating. The visual field defect demonstrated bilateral enlarged blind
      spots and altitudinal defects. Fluorescein angiography (FA) showed nonspecific
      retinal inflammation, and an electroretinogram (ERG) illustrated decreased
      amplitude of the b wave in both eyes. Optical coherence tomography (OCT)
      examinations revealed parafoveal loss of the photoreceptor inner/outer segment
      (IS/OS) junction. Therefore, acute zonal occult outer retinopathy (AZOOR) was
      diagnosed. Although his vision did not improve under the initial treatment of
      systemic corticosteroid and calcium channel blocker, remarkable improvement was
      noticed after the intravitreal injection(IVI) of Ozurdex, consistent with the
      recovered IS/OS junction disruption. CONCLUSIONS: We herein report a typical case
      of AZOOR, suggesting that the intravitreal injection of steroid may benefit in
      certain patients.

PMID- 29207978
TI  - Potential therapeutic effects of N-butylidenephthalide from Radix Angelica
      Sinensis (Danggui) in human bladder cancer cells.
AB  - BACKGROUND: N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis
      (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo
      and in vitro. The effect of BP in bladder cancer treatment is still unclear and
      worth for further investigate. METHODS: Changes of patients with bladder cancer
      after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National
      Health Insurance Research Database (NHIRD) database. The anti-proliferative
      effect of BP on human bladder cancer cells was investigated and their cell cycle
      profiles after BP treatment were determined by flow cytometry. BP-induced
      apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the
      expressions of apoptosis-related proteins were determined by western blot. The
      migration inhibitory effect of BP on human bladder cancer cells were shown by
      trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by
      injection of BFTC human bladder cancer cells. RESULTS: The correlation of taking
      Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this
      herbal product is worth for further investigation. BP caused bladder cancer cell
      death in a time- and dose- dependent manner and induced apoptosis via the
      activation of caspase-9 and caspase-3. BP also suppressed the migration of
      bladder cancer cells as revealed by the trans-well and wound healing assays. Up
      regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real
      time RT-PCR analysis after BP treatment in vitro. Besides, in combination with
      BP, the sensitivity of these bladder cancer cells to cisplatin increased
      significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2%
      reduction of tumor volume after treatment for 26 days. CONCLUSIONS: BP caused
      bladder cancer cell death through activation of mitochondria-intrinsic pathway.
      BP also suppressed the migration and invasion of these cells, probably by
      modulating EMT-related genes. Furthermore, combination therapy of BP with a lower
      dose of cisplatin significantly inhibited the growth of these bladder cancer cell
      lines. The incidence of bladder cancer decreased in patients who were exposed to
      Angelica sinensis, suggesting that BP could serve as a potential adjuvant in
      bladder cancer therapy regimen.

PMID- 29207979
TI  - A propeptide toolbox for secretion optimization of Flavobacterium meningosepticum
      endopeptidase in Lactococcus lactis.
AB  - BACKGROUND: Lactic acid bacteria are a family of "generally regarded as safe"
      organisms traditionally used for food fermentation. In recent years, they have
      started to emerge as potential chassis for heterologous protein production. And
      more recently, due to their beneficial properties in the gut, they have been
      examined as potential candidates for mucosal delivery vectors, especially for
      acid-sensitive enzymes. One such application would be the delivery of gluten
      digesting endopeptidases for the treatment of celiac disease. To facilitate these
      applications, an efficient recombinant protein expression toolbox is required,
      especially for recombinant protein secretion. While current tools for enhancing
      protein secretion consist mainly of signal peptides, secretion propeptides have
      also been observed to play a crucial role for protein secretion and improved
      yields. RESULTS: To expand the propeptide library for secretion optimization, we
      have mined and characterized three naturally occurring propeptides from the
      sequenced genomes of 109 Lactococcus species. These newly-mined propeptides were
      introduced after the N-terminal USP45 secretion signal to characterize and
      compare their effects on the secretion of Escherichia coli thioredoxin (TRX) and
      Flavobacterium meningosepticum prolyl endopeptidase (Fm PEP) in Lactococcus
      lactis NZ9000. All three propeptides, along with the positive control LEISSTCDA,
      improved volumetric secretion yields by 1.4-2.3-folds. However, enhancement of
      secretion yield is dependent on protein of interest. For TRX, the optimal
      combination of USP45 signal peptide and LEISSTCDA produced a 2.3-fold increase in
      secretion yields. Whilst for Fm PEP, propeptide 1 with USP45 signal peptide
      improved volumetric secretion yields by 2.2-fold compared to a 1.4-fold increase
      by LEISSTCDA. Similar trends in Fm PEP activity and protein yield also
      demonstrated minimal effect of the negative charged propeptides on PEP activity
      and thus folding. CONCLUSIONS: Overall, we have characterized three new
      propeptides for use in L. lactis secretion optimization. From success of these
      propeptides for improvement of secretion yields, we anticipate this collection to
      be valuable to heterologous protein secretion optimisation in lactic acid
      bacteria. We have also demonstrated for the first time, secretion of Fm PEP in L.
      lactis for potential use as a therapy agent in celiac disease.

PMID- 29207980
TI  - Pilot randomised controlled trial of culturally adapted cognitive behavior
      therapy for psychosis (CaCBTp) in Pakistan.
AB  - BACKGROUND: Evidence for efficacy of cognitive-behavioural therapy (CBT) in
      treatment of schizophrenia is growing. CBT is effective and cost efficient in
      treating positive and negative symptoms. To effectively meet the needs of diverse
      cultural groups, CBT needs to be adapted to the linguistic, cultural and
      socioeconomic context. We aimed to assess the feasibility, efficacy and
      acceptability of a culturally adapted CBT for treatment of psychosis (CaCBTp) in
      a low-income country. METHODS: Rater-blind, randomised, controlled trial of the
      use of standard duration CBT in patients with psychosis from a low-income
      country. Participants with a ICD-10 diagnosis of psychosis were assessed using
      Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Psychotic Symptom
      Rating Scales (PSYRATS), and the Schedule for Assessment of Insight (SAI)
      (baseline, 3 months and 6 months). They were randomized into the intervention
      group (n = 18) and Treatment As Usual (TAU) group (n = 18). The intervention
      group received 12 weekly sessions of CaCBTp. RESULTS: The CaCBTp group had
      significantly lower scores on PANSS Positive (p = 0.02), PANSS Negative (p =
      0.045), PANSS General Psychopathology (p = 0.008) and Total PANSS (p = 0.05) when
      compared to TAU at three months. They also had low scores on Delusion Severity
      Total (p = 0.02) and Hallucination Severity Total (p = 0.04) of PSYRATS, as well
      as higher scores on SAI (p = 0.01) at the same time point. At six months only the
      improvement in PANSS positive scores (p = 0.045) met statistical significance..
      CONCLUSIONS: It is feasible to offer CaCBTp as an adjunct to TAU in patients with
      psychosis, presenting to services in a lower middle-income country. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier NCT02202694 (Retrospectively
      registered).

PMID- 29207981
TI  - An ontology-aware integration of clinical models, terminologies and guidelines:
      an exploratory study of the Scale for the Assessment and Rating of Ataxia (SARA).
AB  - BACKGROUND: Electronic rating scales represent an important resource for
      standardized data collection. However, the ability to exploit reasoning on rating
      scale data is still limited. The objective of this work is to facilitate the
      integration of the semantics required to automatically interpret collections of
      standardized clinical data. We developed an electronic prototype for the Scale of
      the Assessment and Rating of Ataxia (SARA), broadly used in neurology. In order
      to address the modeling challenges of the SARA, we propose to combine the best
      performances from OpenEHR clinical archetypes, guidelines and ontologies.
      METHODS: A scaled-down version of the Human Phenotype Ontology (HPO) was built,
      extracting the terms that describe the SARA tests from free-text sources. This
      version of the HPO was then used as backbone to normalize the content of the SARA
      through clinical archetypes. The knowledge required to exploit reasoning on the
      SARA data was modeled as separate information-processing units interconnected via
      the defined archetypes. Each unit used the most appropriate technology to
      formally represent the required knowledge. RESULTS: Based on this approach, we
      implemented a prototype named SARA Management System, to be used for both the
      assessment of cerebellar syndrome and the production of a clinical synopsis. For
      validation purposes, we used recorded SARA data from 28 anonymous subjects
      affected by Spinocerebellar Ataxia Type 36 (SCA36). When comparing the
      performance of our prototype with that of two independent experts, weighted kappa
      scores ranged from 0.62 to 0.86. CONCLUSIONS: The combination of archetypes,
      phenotype ontologies and electronic information-processing rules can be used to
      automate the extraction of relevant clinical knowledge from plain scores of
      rating scales. Our results reveal a substantial degree of agreement between the
      results achieved by an ontology-aware system and the human experts.

PMID- 29207982
TI  - On causal roles and selected effects: our genome is mostly junk.
AB  - The idea that much of our genome is irrelevant to fitness-is not the product of
      positive natural selection at the organismal level-remains viable. Claims to the
      contrary, and specifically that the notion of "junk DNA" should be abandoned, are
      based on conflating meanings of the word "function". Recent estimates suggest
      that perhaps 90% of our DNA, though biochemically active, does not contribute to
      fitness in any sequence-dependent way, and possibly in no way at all. Comparisons
      to vertebrates with much larger and smaller genomes (the lungfish and the
      pufferfish) strongly align with such a conclusion, as they have done for the last
      half-century.

PMID- 29207983
TI  - Protocol for project IMPACT (improving millions hearts for provider and community
      transformation): a quasi-experimental evaluation of an integrated electronic
      health record and community health worker intervention study to improve
      hypertension management among South Asian patients.
AB  - BACKGROUND: The Million Hearts(r) initiative aims to prevent heart disease and
      stroke in the United States by mobilizing public and private sectors around a
      core set of objectives, with particular attention on improving blood pressure
      control. South Asians in particular have disproportionately high rates of
      hypertension and face numerous cultural, linguistic, and social barriers to
      accessing healthcare. Interventions utilizing Health information technology (HIT)
      and community health worker (CHW)-led patient coaching have each been
      demonstrated to be effective at advancing Million Hearts(r) goals, yet few
      studies have investigated the potential impact of integrating these strategies
      into a clinical-community linkage initiative. Building upon this initiative, we
      present the protocol and preliminary results of a research study, Project IMPACT,
      designed to fill this gap in knowledge. METHODS: Project IMPACT is a stepped
      wedge quasi-experimental study designed to test the feasibility, adoption, and
      impact of integrating CHW-led health coaching with electronic health record (EHR)
      based interventions to improve hypertension control among South Asian patients in
      New York City primary care practices. EHR intervention components include the
      training and implementation of hypertension-specific registry reports, alerts,
      and order sets. Fidelity to the EHR intervention is assessed by collecting the
      type, frequency, and utilization of intervention components for each practice.
      CHW intervention components consist of health coaching sessions on hypertension
      and related risk factors for uncontrolled hypertensive patients. The outcome,
      hypertension control (<140 mmHg systolic blood pressure (BP) and <90 mmHg
      diastolic BP), is collected at the aggregate- and individual-level for all 16
      clinical practices enrolled. DISCUSSION: Project IMPACT builds upon the evidence
      base of the effectiveness of CHW and Million Hearts(r) initiatives and proposes a
      unique integration of provider-based EHR and community-based CHW interventions.
      The project informs the effectiveness of these interventions in team-based care
      approaches, thereby, helping to develop relevant sustainability strategies for
      improving hypertension control among targeted racial/ethnic minority populations
      at small primary care practices. TRIAL REGISTRATION: This study protocol has been
      approved and is made available on Clinicaltrials.gov by NCT03159533 as of May 17,
      2017.

PMID- 29207984
TI  - Individualised radial extracorporeal shock wave therapy (rESWT) for symptomatic
      calcific shoulder tendinopathy: a retrospective clinical study.
AB  - BACKGROUND: A retrospective single centre cohort analysis was performed to
      evaluate an individualised radial extracorporeal shock wave therapy (rESWT)
      protocol for treatment of symptomatic calcific shoulder tendinopathy. METHODS: 67
      patients (79 Shoulders) were identified with 76 shoulders included for analysis.
      rESWT treatment protocol was adapted according to individual response to
      treatment. Variables included number of sessions, shockwave impulses, pressure
      and frequency. Success rate was estimated as the percentage of patients having
      >=60% visual analogue score (VAS) pain decrease at follow-up. Recurrence at 1
      year was recorded. RESULTS: Using this individualised symptom guided protocol,
      patients underwent a mean of 7 +/- 1.5 rESWT sessions, with mean pressure of 1.7
      +/- 0.2 bar, mean frequency of 5 +/- 0.3 Hz and 2175 +/- 266 impulses. The mean
      pre-treatment VAS score of 6.7 +/- 1.1 was significantly decreased to 3.2 +/- 0.8
      immediately post-treatment, 2.6 +/- 0.9 at 1 month, 1.7 +/- 1.0 at 3 months and
      0.8 +/- 1.0 at 1 year follow up (alpha = 0.05). One-year success rate was
      estimated at 92% and 1-year recurrence rate was 7%. CONCLUSIONS: We conclude that
      in this retrospective study an individualised rESWT protocol resulted in a high
      success rate with low number of recurrences. Randomised controlled trials to
      support these findings are recommended.

PMID- 29207985
TI  - Long-term follow-up after scleral lens fixation in patients with Marfan syndrome.
AB  - BACKGROUND: The dislocation of the crystalline lens is a common finding in
      patients with Marfan syndrome (MFS). Scleral intraocular lens (IOL) fixation is
      an accepted treatment method of this complication. To now, no long-term data on
      scleral IOL fixation in MFS exist. METHODS: We present a retrospective study of
      27 eyes of 17 MFS patients that underwent scleral lens fixation at our clinic
      between 1999 and 2012. These patients are compared to an age- and surgeon-matched
      group of 31 eyes of 27 patients who underwent the same procedure for reasons
      other than MFS. RESULTS: The median age in the MFS group was 35.4 years versus
      35.6 years in the non-MFS group. The median follow-up was 4 years for MFS and 3
      years for non-MFS. In the MFS group, significantly more IOL-dislocations occurred
      than compared to the non-MFS group (30% vs. 6.5%, p = 0.02). Retinal detachment
      occurred in four MFS-eyes compared to three eyes in the non-MFS group. Biometry
      prediction error was 1.11 diopters (D) for MFS and 1.33 D for non-MFS (p = 0.11).
      Median BCVA (best-corrected visual acuity, logMAR) was 0.1 in the MFS group
      versus 0.3 in non-MFS patients. CONCLUSION: Scleral lens fixation in MFS patients
      achieves satisfying visual and refractive outcomes. Our data shows a
      significantly higher rate of IOL dislocations in patients with MFS. We therefore
      recommend addressing this complication preoperatively.

PMID- 29207986
TI  - Risk of total/subtotal meniscectomy for respective medial and lateral meniscus
      injury: correlation with tear type, duration of complaint, age, gender and ACL
      rupture in 6034 Asian patients.
AB  - BACKGROUND: To evaluate the risk factor associated with total or subtotal
      meniscectomy for respective medial and lateral meniscus injury. METHODS: The data
      of all the meniscus injured patients undergoing arthroscopy in our institute
      between January 15th, 2000 and December 31st, 2008 was collected and 6034
      patients with 7241 injured menisci met the inclusion criteria. The mean patient
      age was 33.6 +/- 14.9 years and there were 4785 males and 2456 females with 3568
      medial and 3673 lateral menisci. The decision tree approach was applied to
      investigate the correlation of the tear type, the duration of complaint, age,
      gender, ACL rupture and total/subtotal meniscectomy for respective medial and
      lateral meniscus. RESULTS: The tear type was associated with both medial (chi2 =
      70.901, P < 0.001) and lateral (chi2 = 268.019, P < 0.001) total/subtotal
      meniscectomy. The strongest risk of total/subtotal meniscectomy of both medial
      and lateral meniscus tear was shown for the complex tear followed by the
      longitudinal, oblique, horizontal and radial tear of the medial meniscus and
      followed by horizontal, longitudinal, radial and oblique tear of the lateral
      meniscus. The risk of total/subtotal medial meniscectomy was significantly
      elevated for the patients with complex tear and the age of <=40 years old (chi2 =
      21.028, P < 0.001) and those with the oblique, horizontal or radial tear
      accompanied by ACL rupture (chi2 = 6.631, P = 0.01). Besides, the duration of
      complaint was also associated with total/subtotal meniscectomy of the medial
      longitudinal tear with ACL rupture (chi2 = 17.155, P < 0.001). On the other side,
      the risk of total/subtotal lateral meniscectomy was significantly elevated for
      the complex tear of the female patients (chi2 = 5.877, P = 0.015) with no ACL
      rupture (chi2 = 50.501, P < 0.001). The ACL rupture was associated with a
      decreased risk of total/subtotal meniscectomy for all the types of the lateral
      meniscus (complex: chi2 = 50.501, P < 0.001; horizontal: chi2 = 20.897, P <
      0.001; oblique: chi2 = 27.413, P < 0.001; longitudinal and radial: chi2 = 110.85,
      P < 0.001). CONCLUSION: Analyzing data from a big sample available in an Asian
      patient database, we found different risk factors associated with total/subtotal
      meniscectomy for respective medial and lateral meniscus. Identifying patients at
      high risk for total/subtotal meniscectomy may allow for interventions after
      meniscus injury.

PMID- 29207987
TI  - Correction to: Public-on-private dual practice among physicians in public
      hospitals of Tigray National Regional State, North Ethiopia: perspectives of
      physicians, patients and managers.
AB  - CORRECTION: After the publication of this article [1] it has come to our
      attention that the author Jeph Herrin was incorrectly included as Jeph Henry. The
      correct spelling is included in this erratum and the original article has been
      updated.

PMID- 29207988
TI  - Correction to: An exploration of mortality risk factors in non-severe pneumonia
      in children using clinical data from Kenya.
AB  - CORRECTION: The original article contains an omission in the Acknowledgements sub
      section of the Declarations.

PMID- 29207989
TI  - Case report: continued treatment with alectinib is possible for patients with
      lung adenocarcinoma with drug-induced interstitial lung disease.
AB  - BACKGROUND: Alectinib, a second-generation anaplastic lymphoma kinase (ALK)
      inhibitor, is a key drug for ALK rearranged lung adenocarcinoma. Interstitial
      lung disease (ILD) is an important adverse effect of alectinib, which generally
      requires termination of treatment. However, we treated two patients with drug
      induced ILD who continued to receive alectinib. CASE PRESENTATION: Patient 1 was
      a 57-year-old male with an ALK-rearranged Stage IV lung adenocarcinoma who was
      administered alectinib as first-line therapy. Computed tomography (CT) detected
      asymptomatic ground-glass opacity (GGO) on day 33 of treatment. Alectinib therapy
      was therefore discontinued for 7 days and then restarted. GGO disappeared, and
      the progression of ILD ceased. Patient 2 was a 64-year-old woman with an ALK
      positive lung adenocarcinoma who was administered alectinib as third-line
      therapy. One year later, CT detected GGO; and she had a slight, nonproductive
      cough. Alectinib therapy was continued in the absence of other symptoms, and GGO
      slightly diminished after 7 days. Two months later, CT detected increased GGO,
      and alectinib therapy was continued. GGO diminished again after 7 days. The
      patient has taken alectinib for more than 2 years without progression of ILD.
      CONCLUSIONS: Certain patients with alectinib-induced ILD Grade 2 or less may
      continue alectinib therapy if they are closely managed.

PMID- 29207990
TI  - Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.
AB  - BACKGROUND: The need for novel biomarkers that could aid in non-small cell lung
      cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases
      (MMPs) -1, -2, -7, -9 and -10 in lung tumorigenesis, prompted us to assess the
      diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase
      (TIMP) -1 in NSCLC patients. METHODS: Markers were evaluated in an initial study
      cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were
      analyzed in a larger sample including patients with benign lung diseases. Serum
      MMPs and TIMP-1 were determined by multiplexed immunoassays. Logistic regression
      was employed for multivariate analysis of biomarker combinations. RESULTS: MMPs
      and TIMP-1 were elevated in the serum of NSCLC patients compared to healthy
      controls. MMP-1, -7 and -9 performed at best and were further evaluated in the
      sample including benign pathologies, corroborating the superiority of MMP-9 in
      NSCLC discrimination, also at early-stage NSCLC. The optimal diagnostic value was
      obtained with the model including MMP-9, gender, age and smoking history, that
      demonstrated an AUC of 0.787, 85.54% sensitivity and 64.89% specificity.
      CONCLUSION: Our results suggest that MMP-9 is a potential biomarker for NSCLC
      diagnosis and its combined measurement with other biomarkers could improve NSCLC
      detection.

PMID- 29207992
TI  - Correction to: Chronic obstructive pulmonary disease, bronchial asthma and
      allergic rhinitis in the adult population within the commonwealth of independent
      states: rationale and design of the CORE study.
AB  - After publication of this work [1] it was noticed three author names were spelt
      incorrectly. Liudmila Iashyna should be Liudmyla Iashyna, Marina Polyanskaya
      should be Maryna Polianska and Elcan Mamamdbayov should be Eljan Mammadbayov.

PMID- 29207991
TI  - Investigation of c-KIT and Ki67 expression in normal, preneoplastic and
      neoplastic canine prostate.
AB  - BACKGROUND: c-KIT expression has been related to bone metastasis in human
      prostate cancer, but whether c-KIT expression can be similarly classified in
      canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression
      in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67
      expression were evaluated in forty-four canine prostatic tissues by
      immunohistochemistry, RT-qPCR and western blot. Additionally, we have
      investigated c-KIT protein expression by immunoblotting in two primary canine
      prostate cancer cell lines. RESULTS: Eleven normal prostates, 12 proliferative
      inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two
      prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue
      exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c
      KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed
      positive c-KIT expression. No c-KIT immunoexpression was observed in metastases.
      Canine prostate cancer and PIA samples contained a higher number of Ki67-positive
      cells compared to normal samples. The median relative quantification (RQ) for c
      KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6
      (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A
      positive correlation between the number of Ki67-positive cells and c-KIT
      transcript levels was observed in prostate cancer samples. In the cell line, PC1
      was negative for c-KIT protein expression, while PC2 was weakly positive.
      CONCLUSION: The present study identified a strong correlation between c-KIT
      expression and proliferative index, suggesting that c-KIT may influence cell
      proliferation. Therefore, c-KIT heterogeneous protein expression among the
      samples (five positive and thirteen negative prostate cancer samples) indicates a
      personalized approach for canine prostate cancer.

PMID- 29207993
TI  - Views of policy makers and health promotion professionals on factors facilitating
      implementation and maintenance of interventions and policies promoting physical
      activity and healthy eating: results of the DEDIPAC project.
AB  - BACKGROUND: The uptake, implementation, and maintenance of effective
      interventions promoting physical activity (PA) and a healthy diet and the
      implementation of policies targeting these behaviors are processes not well
      understood. We aimed to gain a better understanding of what health promotion
      professionals and policy makers think are important factors facilitating
      adoption, implementation, and maintenance of multi-level interventions and
      policies promoting healthy eating and PA in Belgium, Germany, Ireland, Norway,
      and Poland. METHODS: Six interventions and six policies were identified based on
      pre-defined criteria. Forty semi-structured interviews were conducted with
      stakeholders from various sectors to elicit information on factors impacting
      adoption, implementation, and maintenance of these interventions and policies.
      All interview transcripts were coded in NVivo, using a common categorization
      matrix. Coding in the respective countries was done by one researcher and
      validated by a second researcher. RESULTS: Active involvement of relevant
      stakeholders and good communication between coordinating organizations were
      described as important factors contributing to successful adoption and
      implementation of both interventions and policies. Additional facilitating
      factors included sufficient training of staff and tailoring of materials to match
      needs of various target groups. The respondents indicated that maintenance of
      implemented interventions/policies depended on whether they were embedded in
      existing or newly created organizational structures in different settings and
      whether continued funding was secured. CONCLUSIONS: Despite considerable
      heterogeneity of interventions and health policies in the five countries,
      stakeholders across these countries identify similar factors facilitating
      adoption, implementation, and maintenance of these interventions and policies.

PMID- 29207994
TI  - The functional and molecular studies on involvement of hydrogen sulphide in
      myometrial activity of non-pregnant buffaloes (Bubalus bubalis).
AB  - BACKGROUND: Hydrogen sulphide (H2S), a member of the gasotransmitters family, is
      known to play patho-physiological role in different body systems including during
      pregnancy. But its involvement in myometrial spontaneity and associated
      signalling pathways in uterus in non-pregnant animals is yet to be studied.
      Present study describes the effect of L-cysteine, an endogenous H2S donor, on
      isolated myometrial strips of non-pregnant buffaloes and the underlying signaling
      mechanism(s). RESULTS: L-cysteine (10 nM-30 mM) produced concentration-dependent
      contractile effect on buffalo myometrium which was extracellular Ca2+ and L-type
      calcium channels-dependent. Significant rightward shift of dose-response curve of
      L-cysteine was observed with significant decrease in maxima in the presence of
      amino-oxyacetic acid (AOAA; 100 MUM) and d, l-propargylglycine (PAG; 100 MUM),
      the specific blockers of cystathionine beta-synthase (CBS) and cystathionine
      gamma-lyase (CSE), respectively. Existence of CBS enzyme of 63 kDa and CSE of 45
      kDa molecular weights was confirmed by western blot using specific antibodies and
      also by immunohistochemistry. CONCLUSIONS: Endogenous H2S along with its
      biosynthetic enzymes (CBS and CSE) is evidently present in uteri of non-pregnant
      buffaloes and it regulates spontaneity in uteri of non-pregnant buffaloes and
      this effect is dependent on extracellular Ca2+ influx through nifedipine
      sensitive L-type calcium channels. Thus H2S-signalling pathway may be a potential
      target to alter the uterine activities in physiology and patho-physiolgical
      states.

PMID- 29207995
TI  - Physicians using spinal manipulative treatment in The Netherlands: a description
      of their characteristics and their patients.
AB  - BACKGROUND: Various health care professionals apply Spinal Manipulative Treatment
      (SMT) in daily practice. While the characteristics of chiropractors and manual
      therapists and the characteristics of their patient populations are well
      described, there is little research about physicians who use SMT techniques. A
      distinct group of physicians in The Netherlands has been trained in
      musculoskeletal (MSK) medicine, which includes the use of SMT. Our objective was
      to describe the characteristics of these physicians and their patient population.
      METHODS: All registered MSK physicians were approached with questionnaires and
      telephone interviews to collect data about their characteristics. Data about
      patient characteristics were extracted from a web-based register. In this
      register physicians recorded basic patient data (age, gender, the type and
      duration of the main complaint, concomitant complaints and the type of referral)
      at the first consultation. Patients were invited to fill in web-based
      questionnaires to provide baseline data about previous treatments and the
      severity of their main complaint. Functional impairment was measured with Patient
      Reported Outcome Measures (PROMs). RESULTS: Questionnaires were sent to 138
      physicians of whom 90 responded (65%). Most physicians were trained in MSK
      medicine after a career in other medical specialities. They reported to combine
      their SMT treatment with a variety of diagnostic and treatment options part of
      which were only permissible for physicians, such as prescription medication and
      injections. The majority of patients presented with complaints of long duration
      (62.1% > 1 year), most frequently low back pain (48.1%) or neck pain (16.9%),
      with mean scores of 6.0 and 6.2, respectively, on a 0 to10 numerical rating scale
      (NRS) for pain intensity. Mean scores on all PROMs showed moderate impairment.
      Patients most frequently reported previous treatment by physical therapists
      (68.1%), manual therapists (37.7%) or chiropractors (17.0%). CONCLUSION: Our
      study showed that MSK physicians in The Netherlands used an array of SMT
      techniques. They embedded their SMT techniques in a broad array of other
      diagnostic and treatment options, part of which were limited to medical doctors.
      Most patients consulted MSK physicians with spinal pain of long duration with
      moderate functional impairment.

PMID- 29207997
TI  - Correction to: Effect of inhaled corticosteroid particle size on asthma efficacy
      and safety outcomes: a systematic literature review and meta-analysis.
AB  - CORRECTION: After publication of this work [1] it was noticed that the author
      name Rachael L. DiSantostefano was not spelt correctly as there was a space in
      her surname between 'Di' and 'Santostefano'. The publisher apologises for this
      error.

PMID- 29207996
TI  - CRISPR-Cas9 mediated gene deletions in lager yeast Saccharomyces pastorianus.
AB  - BACKGROUND: The ease of use of CRISPR-Cas9 reprogramming, its high efficacy, and
      its multiplexing capabilities have brought this technology at the forefront of
      genome editing techniques. Saccharomyces pastorianus is an aneuploid
      interspecific hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus that
      has been domesticated for centuries and is used for the industrial fermentation
      of lager beer. For yet uncharacterised reasons, this hybrid yeast is far more
      resilient to genetic alteration than its ancestor S. cerevisiae. RESULTS: This
      study reports a new CRISPR-Cas9 method for accurate gene deletion in S.
      pastorianus. This method combined the Streptococcus pyogenes cas9 gene expressed
      from either a chromosomal locus or from a mobile genetic element in combination
      with a plasmid-borne gRNA expression cassette. While the well-established gRNA
      expression system using the RNA polymerase III dependent SNR52 promoter failed,
      expression of a gRNA flanked with Hammerhead and Hepatitis Delta Virus ribozymes
      using the RNA polymerase II dependent TDH3 promoter successfully led to accurate
      deletion of all four alleles of the SeILV6 gene in strain CBS1483. Furthermore
      the expression of two ribozyme-flanked gRNAs separated by a 10-bp linker in a
      polycistronic array successfully led to the simultaneous deletion of SeATF1 and
      SeATF2, genes located on two separate chromosomes. The expression of this array
      resulted in the precise deletion of all five and four alleles mediated by
      homologous recombination in the strains CBS1483 and Weihenstephan 34/70
      respectively, demonstrating the multiplexing abilities of this gRNA expression
      design. CONCLUSIONS: These results firmly established that CRISPR-Cas9
      significantly facilitates and accelerates genome editing in S. pastorianus.

PMID- 29207998
TI  - Health workers' perceptions of private-not-for-profit health facilities'
      organizational culture and its influence on retention in Uganda.
AB  - BACKGROUND: An in-depth understanding of how organizational culture is
      experienced by health workers (HWs), and influences their decisions to leave
      their jobs is a fundamental, yet under-examined, basis for forming effective
      retention strategies. This research examined HWs' working experiences and
      perceptions of organisational culture within private-not-for-profit, largely
      mission-based hospitals, and how this influenced retention. METHODS: Thirty-two
      HWs, including managers, in 19 health facilities in Uganda were interviewed using
      a semi-structured topic guide. Interview transcripts were analysed using thematic
      content analysis. RESULTS: Interviews showed that the organizational culture was
      predominantly hierarchical, with non-participative management styles which
      emphasized control and efficiency. HWs and managers held different perceptions of
      the organizational culture. While the managers valued results and performance,
      HWs valued team work, recognition and participative management. CONCLUSIONS: The
      findings of this study indicate that organizational culture influences retention
      of HWs in health facilities and provide a useful context to inform health care
      managers in the PNFP sub-sector in Uganda and similar contexts. To improve
      retention of HWs, a gradual shift in organizational culture will be necessary,
      focussing on the values, beliefs and perceptions which have the greatest
      influence on observable behaviour.

PMID- 29207999
TI  - Corticosteroid plus beta2-agonist in a single inhaler as reliever therapy in
      intermittent and mild asthma: a proof-of-concept systematic review and meta
      analysis.
AB  - BACKGROUND: Current guidelines recommend a single inhaler maintenance and
      reliever therapy (SMART) regimen for moderate to severe asthma. However, evidence
      for the inhaled corticosteroid plus fast-onset-acting beta2-agonist (ICS/FABA) as
      reliever therapy in management of intermittent and mild asthma patients is
      lacking. OBJECTIVE: To systematically explore efficacy and safety of the proof-of
      concept of the ICS plus FABA regimen in a single inhaler as reliever therapy
      across children and adults with intermittent and mild persistent asthma. METHODS:
      We searched online bibliographic databases for randomized controlled trials
      (RCTs) involving the as-needed use of ICS/FABA as monotherapy in intermittent or
      mild asthma patients. The primary outcomes were exacerbations and the hazard
      ratio (HR) of the time to first exacerbation. RESULTS: Six RCTs (n = 1300) met
      the inclusion criteria. Compared with the as-needed FABA regimen, the as-needed
      use of ICS/FABA as monotherapy statistically reduced exacerbations (RR = 0.56, P
      = 0.001). Compared with regular ICS regimen, the as-needed ICS/FABA therapy had
      slightly higher risk of exacerbations (RR = 1.39, P = 0.011). The HR for time to
      first exacerbations in the ICS/FABA regimen was significant lower when compared
      with FABA regimen (HR = 0.52, P = 0.002) but had no difference when compared with
      ICS regimen (HR = 1.30, P = 0.286). The corticosteroid exposure in the daily ICS
      regimen was 2- to 5-fold compared with as-needed use of ICS/FABA regimen.
      CONCLUSIONS: Our analysis shows that the ICS/FABA as a symptom-driven therapy may
      be a promising alternative regimen for the patients with intermittent or mild
      asthma, but it needs further real-world RCTs to confirm these findings.

PMID- 29208000
TI  - Dynamics behind the scale up of evidence-based obesity prevention: protocol for a
      multi-site case study of an electronic implementation monitoring system in health
      promotion practice.
AB  - BACKGROUND: The effectiveness of many interventions to promote health and prevent
      disease has been well established. The imperative has therefore shifted from
      amassing evidence about efficacy to scale-up to maximise population-level health
      gains. Electronic implementation monitoring, or 'e-monitoring', systems have been
      designed to assist and track the delivery of preventive policies and programs.
      However, there is little evidence on whether e-monitoring systems improve the
      dissemination, adoption, and ongoing delivery of evidence-based preventive
      programs. Also, given considerable difficulties with e-monitoring systems in the
      clinical sector, scholars have called for a more sophisticated re-examination of
      e-monitoring's role in enhancing implementation. METHODS: In the state of New
      South Wales (NSW), Australia, the Population Health Information Management System
      (PHIMS) was created to support the dissemination of obesity prevention programs
      to 6000 childcare centres and elementary schools across all 15 local health
      districts. We have established a three-way university-policymaker-practice
      research partnership to investigate the impact of PHIMS on practice, how PHIMS is
      used, and how achievement of key performance indicators of program adoption may
      be associated with local contextual factors. Our methods encompass ethnographic
      observation, key informant interviews and participatory workshops for data
      interpretation at a state and local level. We use an on-line social network
      analysis of the collaborative relationships across local health district health
      promotion teams to explore the relationship between PHIMS use and the
      organisational structure of practice. DISCUSSION: Insights will be sensitised by
      institutional theory, practice theory and complex adaptive system thinking, among
      other theories which make sense of socio-technical action. Our working hypothesis
      is that the science of getting evidence-based programs into practice rests on an
      in-depth understanding of the role they play in the on-going system of local
      relationships and multiple accountabilities. Data will be synthesised to produce
      a typology to characterise local context, PHIMS use and key performance indicator
      achievement (of program implementation) across the 15 local health districts.
      Results could be used to continuously align e-monitoring technologies within
      quality improvement processes to ensure that such technologies enhance practice
      and innovation. A partnership approach to knowledge production increases the
      likelihood that findings will be put into practice.

PMID- 29208001
TI  - Factors associated with infants' and young children's (6-23 months) dietary
      diversity in Pakistan: evidence from the demographic and health survey 2012-13.
AB  - BACKGROUND: Optimum nutrition and good feeding practices amongst infants and
      young children are the key determinants of growth for a healthy life. Dietary
      diversity is considered to be a reliable and easy-to-measure proxy variable to
      assess young children's feeding practices for dietary adequacy and nutritional
      intake. This research aims to examine the current practices of dietary diversity
      amongst infants and young children aged 6-23 months in Pakistan and the various
      associated factors at child, maternal, household and community levels. METHODS:
      Secondary data analysis was performed for this research using the nationally
      representative dataset of the Pakistan Demographic and Health Survey 2012-13.
      Data on the last-born infants and young children aged 6-23 months (n = 1102) was
      taken from their mothers' interviews, who reported on their child's consumption
      of 7 food groups during the 24 h immediately preceding the survey. Data was
      analysed, using IBM(r) SPSS(r) Complex Sample to measure the association between
      children's dietary diversity and various factors at child, maternal, household
      and community levels through multiple linear regressions. RESULTS: Our research
      uncovered positive associations between children's dietary diversity and other
      sociodemographic variables. Overall, a variation was observed in consumption of 7
      food groups across the youngest, middle and oldest age-groups of children.
      Multivariate analysis revealed that the children's Dietary Diversity Score (scale
      from 0 to 7) increases to 0.56 (95% CI: 0.18-0.94) amongst children in the middle
      age-group (12-17 months). Furthermore, the children who were still breastfeeding,
      with mothers who had a primary level of schooling and whose mothers also received
      information/services from lady health workers (LHWs) on maternal and child health
      were found to be a statistically significant predictor of infants' and young
      children's dietary diversity. Nevertheless, amongst them, the DDS had a negative
      association with the children's status of still breastfeeding and mothers'
      primary level of schooling, whereas it had a positive association with children
      being in the middle age-group and with mothers who received information/services
      from LHWs. CONCLUSION: The dietary diversity of infants and young children aged 6
      23 months has a modest, nevertheless statistically significant, relationship with
      sociodemographic characteristics in Pakistan. There is a need for practical
      efforts to change the behaviour of communities to encourage more diverse foods to
      promote the healthy growth of children.

PMID- 29208002
TI  - EPHA6 rs4857055 C > T polymorphism associates with hypertension through
      triglyceride and LDL particle size in the Korean population.
AB  - BACKGROUND: Erythropoietin-producing human hepatocellular (Eph) receptors might
      contribute to the development of atherosclerosis. A genome-wide association study
      indicated that the Eph receptor A6 gene (EPHA6) associated with at least 1 blood
      pressure (BP) phenotype. The objective of the present study was to determine
      whether EPHA6 is a novel candidate gene for hypertension in a Korean population.
      METHODS: A total 2146 study participants with normotension and hypertension were
      included. Genotype data were obtained using a Korean Chip. To assess the
      association between single-nucleotide polymorphisms (SNPs) and BP, we performed a
      linear regression analysis, which showed that rs4850755 in the EPHA6 gene was the
      SNP most highly associated with both systolic and diastolic BP. RESULTS: The
      presence of the TT genotype of the EPHA6 rs4857055 C > T SNP was associated with
      a higher risk of hypertension after adjusting for age, sex, body mass index
      (BMI), smoking, and drinking [odds ratio 1.533, P = 0.001]. In the control group,
      significant associations were observed between systolic BP and the rs4857055
      polymorphism and between diastolic BP and the rs4857055 polymorphism. In the
      hypertension group, a significant association was observed between systolic BP
      and the rs4857055 polymorphism. In the hypertension group, subjects with the TT
      genotype showed significantly higher systolic BP than CC subjects. Additionally,
      in the hypertension group, TT carriers showed a higher tendency of serum
      triglyceride (P = 0.069) and significantly higher apolipoprotein B (P = 0.015)
      and smaller low-density lipoprotein (LDL) particle size (P < 0.001) than either
      TC or CC subjects. CONCLUSIONS: These results could suggest that the EPHA6
      rs4857055 C > T SNP is a novel candidate gene for hypertension in the Korean
      population. Additionally, the TT genotype could be associated with
      hypertriglyceridemia and small LDL particle size in hypertension.

PMID- 29208003
TI  - FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1
      expression in male patients.
AB  - BACKGROUND: Forkhead box A1 (FOXA1) expression is associated with various types
      of tumors; however, the function and underlying mechanism of FOXA1 in the
      development of hepatocellular carcinoma (HCC) remains obscure. METHODS: Here, we
      investigated the role of FOXA1 in the development of HCC by applying gene
      function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing
      outcomes with those of clinical HCC samples. RESULTS: Phosphoinositide-3-kinase
      regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was
      identified as a FOXA1 target gene. Analyses of the mechanism and function
      revealed that FOXA1 suppresses hepatocellular carcinoma cell viability and
      motility by inhibiting PI3K/Akt signaling through direct inhibition of PIK3R1
      transcription. Moreover, in clinical samples from male HCC patients, FOXA1
      expression was much lower, whereas PI3Kp85 levels were much higher in tumor than
      in non-tumor tissues. Elevated PI3Kp85 is an unfavorable factor in HCC.
      CONCLUSIONS: As a tumor suppressor, FOXA1 targets PIK3R1 directly to inhibit
      PI3K/Akt signaling pathway, thus exerting a negative regulatory effect on
      proliferation, migration, and invasion of HCC in male patients.

PMID- 29208004
TI  - Psychometric properties of the single-item measure, severity of worst tiredness,
      in patients with moderately to severely active rheumatoid arthritis.
AB  - BACKGROUND: To assess the reliability, validity, and responsiveness to treatment
      change of the single-item measure, Severity of Worst Tiredness, in patients with
      rheumatoid arthritis (RA). METHODS: Data from two Phase 3, randomized, placebo
      controlled (RA-BUILD; and active-controlled [RA-BEAM]), clinical studies of the
      efficacy of baricitinib in adults with moderately to severely active RA were
      used. The psychometric properties of the single-item measure, Severity of Worst
      Tiredness, were assessed, including test-retest reliability, convergent and
      discriminant validity, known-groups validity, and responsiveness, using other
      patient- and clinician-reported outcomes frequently assessed in RA patients.
      RESULTS: Test-retest reliability of the Severity of Worst Tiredness was supported
      through large intraclass correlation coefficients (0.89 <= ICC <= 0.91). Moderate
      to-large correlations were observed between this patient-reported outcome (PRO)
      and other related patient- and clinician-reported assessments of RA symptoms and
      patient functioning, supporting construct validity of the measure (?r? >= 0.41).
      The instrument also displayed known-groups validity through statistically
      significant differences between mean values of the Severity of Worst Tiredness
      defined using other indicators of RA severity. Finally, responsiveness was
      supported by large and statistically significant differences in change scores
      from Day 1 to Week 12 for patients comparing responders and nonresponders using
      the American College of Rheumatology 20 (ACR20) criteria. CONCLUSION: The
      Severity of Worst Tiredness PRO demonstrated adequate reliability, validity, and
      responsiveness in clinical trials of adults with moderately to severely active RA
      and is fit for purpose in this patient population.

PMID- 29208005
TI  - Recovery after critical illness: putting the puzzle together-a consensus of 29.
AB  - In this review, we seek to highlight how critical illness and critical care
      affect longer-term outcomes, to underline the contribution of ICU delirium to
      cognitive dysfunction several months after ICU discharge, to give new insights
      into ICU acquired weakness, to emphasize the importance of value-based
      healthcare, and to delineate the elements of family-centered care. This consensus
      of 29 also provides a perspective and a research agenda about post-ICU recovery.

PMID- 29208006
TI  - Identification and validation of a 44-gene expression signature for the
      classification of renal cell carcinomas.
AB  - BACKGROUND: Renal cancers account for more than 3% of all adult malignancies and
      cause more than 23,400 deaths per year in China alone. The four most common types
      of kidney tumours include clear cell, papillary, chromophobe and benign
      oncocytoma. These histological subtypes vary in their clinical course and
      prognosis, and different clinical strategies have been developed for their
      management. Some kidney tumours can be very difficult to distinguish based on the
      pathological assessment of morphology and immunohistochemistry. METHODS: Six
      renal cell carcinoma microarray data sets, including 106 clear cell, 66
      papillary, 42 chromophobe, 46 oncocytoma and 35 adjacent normal tissue samples,
      were subjected to integrative analysis. These data were combined and used as a
      training set for candidate gene expression signature identification. In addition,
      two independent cohorts of 1020 RNA-Seq samples from The Cancer Genome Atlas
      database and 129 qRT-PCR samples from Fudan University Shanghai Cancer Center
      (FUSCC) were analysed to validate the selected gene expression signature.
      RESULTS: A 44-gene expression signature derived from microarray analysis was
      strongly associated with the histological differentiation of renal tumours and
      could be used for tumour subtype classification. The signature performance was
      further validated in 1020 RNA-Seq samples and 129 qRT-PCR samples with overall
      accuracies of 93.4 and 93.0%, respectively. CONCLUSIONS: A 44-gene expression
      signature that could accurately discriminate renal tumour subtypes was identified
      in this study. Our results may prompt further development of this gene expression
      signature into a molecular assay amenable to routine clinical practice.

PMID- 29208007
TI  - A pilot study to determine the effect of one physical therapy session on physical
      activity levels for individuals with chronic low back pain.
AB  - BACKGROUND: A pilot study was conducted to quantify the effect size of changes in
      physical activity after of one session of physical therapy for individuals with
      chronic low back pain and to determine factors that predict daily sedentary
      activity time. METHODS: Fourteen subjects with at least 3 days of physical
      activity accelerometer data were analyzed before and after one session of
      physical therapy. Data was analyzed using 1-tailed, paired t-tests with level of
      significance set at 0.05. Effect sizes were computed using the baseline and post
      intervention mean differences divided by the baseline and post-intervention
      differences in the standard deviation. RESULTS: A nonsignificant reduction in
      steps-per-day and time spent performing sedentary activities, with increases in
      light and moderate-vigorous physical activity were found (effect size: 0.15
      0.33). A nonsignificant decrease in daily sitting and standing time 1 week
      immediately following the physical therapy session and an increase in daily lying
      time (p = 0.03) (effect size: 0.23-0.69) were found. CONCLUSION: One physical
      therapy session resulted in a small physical activity change for individuals with
      chronic low back pain. Baseline and post intervention levels of pain
      catastrophisation and perceptions of disability need to be explored in future
      studies to determine if these are factors that influence levels of physical
      activity change for these individuals Results are limited by the small sample
      size, however the ability to increase physical activity in this population may be
      of clinical relevance. Trial Registration NCT02823756; June 30, 2016:
      Retrospectively Registered.

PMID- 29208009
TI  - Troglostrongylus brevior: a new parasite for Romania.
AB  - BACKGROUND: The genus Troglostrongylus includes nematodes infecting domestic and
      wild felids. Troglostrongylus brevior was described six decades ago in Palestine
      and subsequently reported in some European countries (Italy, Spain, Greece,
      Bulgaria, and Bosnia and Herzegovina). As the diagnosis by the first-stage larvae
      (L1) may be challenging, there is a possibility of confusion with
      Aelurostrongylus abstrusus. Hence, the knowledge on the distribution of this
      neglected feline parasite is still scarce. The present paper reports the first
      case of T. brevior infection in Romania. In July 2017, a road-killed juvenile
      male Felis silvestris, was found in in Covasna County, Romania. A full necropsy
      was performed and the nematodes were collected from the trachea and bronchioles.
      Parasites were sexed and identified to species level, based on morphometrical
      features. A classical Baermann method was performed on the lungs and the faeces
      to collect the metastrongyloid larvae. Genomic DNA was extracted from an adult
      female nematode. Molecular identification was accomplished with a PCR assay
      targeting the ITS2 of the rRNA gene. RESULTS: Two males and one female nematodes
      were found in the trachea and bronchioles. They were morphologically and
      molecularly identified as T. brevior. The first-stage larvae (L1) recovered from
      the lung tissue and faeces were morphologically consistent with those of T.
      brevior. No other pulmonary nematodes were identified and no gross pulmonary
      lesions were observed. CONCLUSIONS: This paper represents the first report of
      Troglostrongylus brevior infection in Romania, so far representing the second
      northernmost location for this genus in Europe. The diversity of species
      infecting wild and domestic felids and the differences regarding the clinical
      significance of these nematodes highlight the need for a more intense
      surveillance and proper diagnosis of feline lungworm infections, especially in
      countries where more species were demonstrated to be present. Furthermore, an
      increased awareness between clinicians is needed for a correct diagnostic
      approach to feline lungworm diagnosis.

PMID- 29208008
TI  - "I just feel comfortable out here, there's something about the place": staff and
      client perceptions of a remote Australian Aboriginal drug and alcohol
      rehabilitation service.
AB  - BACKGROUND: The need for effective, culturally safe residential rehabilitation
      services for Aboriginal people is widely acknowledged, however the combination of
      treatment components that is optimally effective, is not well defined. Most
      existing Aboriginal residential rehabilitation research has focused on describing
      client characteristics, and largely ignored the impact of treatment and service
      factors, such as the nature and quality of therapeutic components and
      relationships with staff. METHODS: This qualitative study was undertaken as part
      of a three-year mixed methods community-based participatory research (CBPR)
      project that aimed to empirically describe a remote Aboriginal drug and alcohol
      rehabilitation service. Researchers utilised purposive sampling to conduct 21 in
      depth, semi-structured interviews. The interviews used a 'research yarning'
      approach, a form of culturally appropriate conversation that is relaxed and
      narrative-based. The interview transcripts were thematically coded using
      iterative categorization. The emerging themes were then analysed from an
      Interpretative Phenomenological Analysis, focusing on how participants' lived
      experiences before and during their admission to the service shaped their
      perceptions of the program. RESULTS: A total of 12 clients (mean age 35 years, SD
      9.07, 91% Aboriginal) and 9 staff (2 female, 7 male, mean age 48 years, SD 8.54,
      67% Aboriginal) were interviewed. Five themes about specific program components
      were identified in the interview data: healing through culture and country;
      emotional safety and relationships; strengthening life skills; improved
      wellbeing; and perceived areas for improvement. This research found that
      Aboriginal drug and alcohol residential rehabilitation is not just about length
      of time in treatment, but also about the culture, activities and relationships
      that are part of the treatment process. CONCLUSION: This study highlights that
      cultural elements were highly valued by both clients and staff of a remote
      Aboriginal residential rehabilitation service, with the country or location being
      fundamental to the daily practice of, and access to, culture. Developing reliable
      and valid assessments of the program components of culture and treatment alliance
      would be valuable, given this study has reinforced their perceived importance in
      achieving positive treatment outcomes. Further, strengthening the aftercare
      program, as part of an integrated model of care, would likely provide greater
      support to clients after discharge.

PMID- 29208010
TI  - Prediction of progression of damage to articular cartilage 2 years after anterior
      cruciate ligament reconstruction: use of aggrecan and type II collagen biomarkers
      in a retrospective observational study.
AB  - BACKGROUND: We aimed to determine whether synovial fluid (SF) biomarkers can
      predict the progression of articular cartilage damage as determined by
      arthroscopic evaluation during and after anterior cruciate ligament (ACL)
      reconstruction. METHODS: Arthroscopic assessment of articular cartilage damage
      was performed twice in 62 patients, first during ACL reconstruction and then
      approximately 2 years later during implant removal for ligament fixation. SF
      levels of the collagenase-generated cleavage neoepitope of type II collagen (C2C)
      and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate
      (Deltadi-C4S), and chondroitin-6-sulfate (Deltadi-C6S) were measured at ACL
      reconstruction. Associations between baseline biomarker levels and subsequent
      progression of cartilage damage were determined using receiver operating
      characteristic analysis and multivariable logistic regression analysis. RESULTS:
      No radiographic changes were observed in any of the patients. Progression of high
      grade cartilage damage, observed arthroscopically, was negatively correlated with
      levels of Deltadi-C6S and KS, as well as the ratio of Deltadi-C6S to Deltadi-C4S
      (C6S/C4S). Logistic regression analysis revealed significant associations of
      Deltadi-C6S (cut-off: 55.7 nmol/ml, odds ratio (OR) 0.231, 95% confidence
      interval (CI) 0.061-0.879), KS (cut-off: 10.6 MUg/ml, OR 0.114, 95% CI 0.024
      0.529), and C6S/C4S ratio (cut-off: 4.6, OR 0.060, 95% CI 0.005-0.737) with the
      progression of high-grade cartilage damage after adjusting for age, the duration
      from injury to first surgery, sex, and the number of high-grade lesions (grades
      III and IV) at baseline. CONCLUSIONS: The progression of high-grade cartilage
      damage was significantly associated with baseline levels of proteoglycan
      glycosaminoglycan biomarkers; namely, Deltadi-C6S, KS, and C6S/C4S ratio.

PMID- 29208011
TI  - Babesia vesperuginis, a neglected piroplasmid: new host and geographical records,
      and phylogenetic relations.
AB  - BACKGROUND: Babesia spp. are hemoparasites which infect the red blood cells of a
      large variety of mammals. In bats, the only known species of the genus is Babesia
      vesperuginis. However, except a few old reports, the host range and geographical
      distribution of this bat parasite have been poorly studied. This study aimed to
      investigate the presence of piroplasms in tissues of bats collected in four
      different countries from eastern and central Europe: Austria, Czech Republic,
      Hungary and Romania. METHODS: A total of 461 bat carcasses (24 species) were
      collected between 2001 and 2016 from caves, mines and buildings. PCR was
      performed using specific primers targeting a portion of the 18S rDNA nuclear gene
      and cytochrome c oxidase subunit 1 mitochondrial gene, followed by sequencing.
      RESULTS: The results of this study show for the first time the presence of B.
      vesperuginis in bats in central and eastern Europe. The phylogenetic analysis of
      the 18S rDNA nuclear gene revealed no variability between the sequences and the
      phylogenetic analysis of the cox1 mitochondrial gene proved that B. vesperuginis
      could be divided into two subclades. CONCLUSION: Our study showed a broad
      geographical distribution of B. vesperuginis in European bats, reporting its
      presence in five new host species (M. cf. alcathoe, M. bechsteinii, M. myotis,
      Pi. nathusii and V. murinus) and three new countries.

PMID- 29208012
TI  - Pho dynamically interacts with Spt5 to facilitate transcriptional switches at the
      hsp70 locus.
AB  - BACKGROUND: Numerous target genes of the Polycomb group (PcG) are transiently
      activated by a stimulus and subsequently repressed. However, mechanisms by which
      PcG proteins regulate such target genes remain elusive. RESULTS: We employed the
      heat shock-responsive hsp70 locus in Drosophila to study the chromatin dynamics
      of PRC1 and its interplay with known regulators of the locus before, during and
      after heat shock. We detected mutually exclusive binding patterns for HSF and
      PRC1 at the hsp70 locus. We found that Pleiohomeotic (Pho), a DNA-binding PcG
      member, dynamically interacts with Spt5, an elongation factor. The dynamic
      interaction switch between Pho and Spt5 is triggered by the recruitment of HSF to
      chromatin. Mutation in the protein-protein interaction domain (REPO domain) of
      Pho interferes with the dynamics of its interaction with Spt5. The
      transcriptional kinetics of the heat shock response is negatively affected by a
      mutation in the REPO domain of Pho. CONCLUSIONS: We propose that a dynamic
      interaction switch between PcG proteins and an elongation factor enables stress
      inducible genes to efficiently switch between ON/OFF states in the
      presence/absence of the activating stimulus.

PMID- 29208013
TI  - Patients and surgeons provide endorsement of core domains for total joint
      replacement clinical trials.
AB  - BACKGROUND: Our objective in this study was to examine whether stakeholders
      further endorse the core domain set proposed by the Outcome Measures in
      Rheumatology Trials (OMERACT) total joint replacement (TJR) working group.
      METHODS: We emailed a survey to 3810 hip/knee arthroplasty patients and 49
      arthroplasty surgeons at a high-volume arthroplasty center to rate the importance
      of each core domain (i.e., pain, function, patient satisfaction, revision
      surgery, adverse events, and death) and two additional domains (i.e., cost and
      participation). Ratings were on a 1-9 scale, with 1-3 indicating limited or no
      importance for patients, 4-6 being important but not critical, and 7-9 being
      critical. We calculated median (IQR) values and compared ratings by sex, age, and
      participant type using the Wilcoxon rank-sum test. RESULTS: The questionnaire was
      completed by 1295 patients (34%) and 21 surgeons (43%). Patient nonresponders
      were similar to responders in age (>=55 years, 85.7% vs. 88.6%), sex (female,
      57.5% vs. 57.3%), and joint procedure (total hip replacement, 56.9% vs. 63.2%).
      Overall, all core domains and one noncore domain (i.e., participation) were
      confirmed as "critical" by both stakeholder groups. Cost was rated as only
      "important" but not "critical" by surgeons. A completed consensus for all the
      core domains persisted even when we stratified by sex, age, arthritis type, and
      the affected joint (knee vs. hip). We received suggestions for additional
      critical domains from 217 patients and 5 surgeons, prompting the inclusion of 2
      research agenda items. CONCLUSIONS: Our study confirmed a consensus rating of the
      OMERACT TJR core domain set as critical for patients. This broad endorsement
      should encourage the identification of candidate outcome instruments to further
      develop a TJR core measurement set that can harmonize reporting in TJR clinical
      trials.

PMID- 29208014
TI  - Plasma C4d as marker for lupus nephritis in systemic lupus erythematosus.
AB  - BACKGROUND: In the present study, we sought to evaluate the complement activation
      product C4d as a marker for lupus nephritis in systemic lupus erythematosus
      (SLE). METHODS: C4d levels were determined by enzyme-linked immunosorbent assay
      in plasma samples of patients with established SLE using a novel approach based
      on detection of a short linear cleavage neoepitope. Cross-sectional associations
      were studied in 98 patients with SLE with samples taken at lower or higher
      respective disease activity. Temporal associations were investigated in 69
      patients with SLE who were followed longitudinally for up to 5 years. Plasma
      samples from 77 healthy donors were included as controls. RESULTS: C4d levels
      were negligible in healthy control subjects and significantly increased in
      patients with SLE in the cross-sectional study (p < 0.0001). C4d levels
      discriminated between higher and lower disease activity according to ROC curve
      analysis (p < 0.001), exhibiting a positive predictive value of 68%. At higher
      disease activity, C4d levels correlated with the modified Systemic Lupus
      Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus
      nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with
      nephritis. High C4d levels together with the presence of anti-dsDNA
      autoantibodies preceded and thus predicted future lupus nephritis in the
      longitudinal study (OR 5.4, 95% CI 1.4-21.3). When we considered only patients
      with renal involvement (19 of 69) during the longitudinal study, we found that
      high C4d levels alone could forecast recurrence of future lupus nephritis (OR
      3.3, 95% CI 1.2-9.6). CONCLUSIONS: C4d appears to be a valuable marker for use in
      monitoring of patients with SLE, particularly for lupus nephritis. Importantly,
      C4d levels can predict impending flares of lupus nephritis and may thus be useful
      for informing treatment.

PMID- 29208015
TI  - Molecular etiological profile of atypical bacterial pathogens, viruses and
      coinfections among infants and children with community acquired pneumonia
      admitted to a national hospital in Lima, Peru.
AB  - OBJECTIVE: The main objective of this study was to detect the presence of 14
      respiratory viruses and atypical bacteria (Mycoplasma pneumoniae, Chlamydia
      pneumoniae), via polymerase chain reaction in patients under 18 years old
      hospitalized due to community-acquired pneumonia (CAP) from Lima, Peru. RESULTS:
      Atypical pathogens were detected in 40% (58/146); viral etiologies in 36%
      (52/146) and coinfections in 19% (27/146). The most common etiological agent was
      M. pneumoniae (n = 47), followed by C. pneumoniae (n = 11). The most frequent
      respiratory viruses detected were: respiratory syncytial virus A (n = 35),
      influenza virus C (n = 21) and parainfluenza virus (n = 10). Viral-bacterial and
      bacterium-bacterium coinfections were found in 27 cases. In our study population,
      atypical bacteria (40%) were detected as frequently as respiratory viruses (36%).
      The presence of M. pneumoniae and C. pneumoniae should not be underestimated as
      they can be commonly isolated in Peruvian children with CAP.

PMID- 29208016
TI  - Production and characterization of anti-Campylobacter jejuni IgY derived from egg
      yolks.
AB  - BACKGROUND: Campylobacter jejuni is a major cause of foodborne disease having
      chickens as an important reservoir. Its control at the farm would lower the
      contamination of the final products and therefore also lower the risk of
      transmission to humans. At the farm, C. jejuni is rarely found in chickens before
      they reach 2 weeks of age. Past studies have shown that maternal antibodies could
      hamper C. jejuni gut colonization. The objective of this study was to compare
      protocols to use in order to produce anti-C. jejuni antibodies derived from egg
      yolks in the perspective to be used as feed additives for the control of chicken
      C. jejuni colonization. Laying hens were naturally contaminated with four well
      characterized strains or injected with either outer membrane proteins or formalin
      killed whole bacteria derived from these same strains. Eggs were collected and
      IgYs present in the yolks were extracted. The amount and the specificity of the
      recovered antibodies were characterized. RESULTS: It was observed that injection
      yielded eggs with superior concentrations of both total and anti-C. jejuni
      antibodies. Equivalent performances for antibodies recovered from all protocols
      were observed for the ability of the antibodies to agglutinate the live C. jejuni
      homologous strains, to hinder their motility or to lyse the bacteria. Western
      blot analyses showed that proteins from all strains could be recognized by all
      IgY extracts. All these characteristics were strain specific. The
      characterization assays were also made for heterologous strains and weaker
      results were observed when compared to the homologous strains. CONCLUSIONS: Based
      on these results, only an IgY quantitative based selection can be made in regards
      to which protocol would give the best anti-C. jejuni IgY enriched egg-yolks as
      all tested protocols were equivalent in terms of the recovered antibody ability
      to recognized the tested C. jejuni strains.

PMID- 29208017
TI  - A multisession evaluation of an adaptive competitive arm rehabilitation game.
AB  - BACKGROUND: People with neurological injuries such as stroke should exercise
      frequently and intensely to regain their motor abilities, but are generally
      hindered by lack of motivation. One way to increase motivation in rehabilitation
      is through competitive exercises, but such exercises have only been tested in
      single brief sessions and usually did not adapt difficulty to the patient's
      abilities. METHODS: We designed a competitive arm rehabilitation game for two
      players that dynamically adapts its difficulty to both players' abilities. This
      game was evaluated by two participant groups: 15 participants with chronic arm
      impairment who exercised at home with an unimpaired friend or relative, and 20
      participants in the acute or subacute phase of stroke who exercised in pairs (10
      pairs) at a rehabilitation clinic. All participants first played the game against
      their human opponent for 3 sessions, then played alone (against a computer
      opponent) in the final, fourth session. In all sessions, participants' subjective
      experiences were assessed with the Intrinsic Motivation Inventory questionnaire
      while exercise intensity was measured using inertial sensors built into the
      rehabilitation device. After the fourth session, a final brief questionnaire was
      used to compare competition and exercising alone. RESULTS: Participants who
      played against an unimpaired friend or relative at home tended to prefer
      competition (only 1 preferred exercising alone), and exhibited higher enjoyment
      and exercise intensity when competing (first three sessions) than when exercising
      alone (last session). Participants who played against each other in the clinic,
      however, did not exhibit significant differences between competition and
      exercising alone. For both groups, there was no difference in enjoyment or
      exercise intensity between the first three sessions, indicating no negative
      effects of habituation or novelty. CONCLUSIONS: Competitive exercises have high
      potential for unsupervised home rehabilitation, as they improve enjoyment and
      exercise intensity compared to exercising alone. Such exercises could thus
      improve rehabilitation outcome, but this needs to be tested in long-term clinical
      trials. It is not clear why participants who competed against each other at the
      clinic did not exhibit any advantages of competition, and further studies are
      needed to determine how different factors (environment, nature of opponent etc.)
      influence patients' experiences with competitive exercises. TRIAL REGISTRATION:
      The study is not a clinical trial. While human subjects are involved, they do not
      participate in a full rehabilitation intervention, and no health outcomes are
      examined.

PMID- 29208018
TI  - Noise exposure during prehospital emergency physicians work on Mobile Emergency
      Care Units and Helicopter Emergency Medical Services.
AB  - BACKGROUND: Prehospital personnel are at risk of occupational hearing loss due to
      high noise exposure. The aim of the study was to establish an overview of noise
      exposure during emergency responses in Mobile Emergency Care Units (MECU),
      ambulances and Helicopter Emergency Medical Services (HEMS). A second objective
      was to identify any occupational hearing loss amongst prehospital personnel.
      METHODS: Noise exposure during work in the MECU and HEMS was measured using
      miniature microphones worn laterally to the auditory canals or within the
      earmuffs of the helmet. All recorded sounds were analysed in proportion to a
      known tone of 94 dB. Before and after episodes of noise exposure, the physicians
      underwent a hearing test indicating whether the noise had had any impact on the
      function of the outer sensory hair cells. This was accomplished by measuring the
      amplitude level shifts of the Distortion Product Otoacoustic Emissions.
      Furthermore, the prehospital personnels' hearing was investigated using pure-tone
      audiometry to reveal any occupational hearing loss. All prehospital personnel
      were compared to ten in-hospital controls. RESULTS: Our results indicate high
      noise exposure levels of >=80 dB(A) during use of sirens on the MECU and during
      HEMS operations compared to in-hospital controls (70 dB(A)). We measured an
      exposure up to >=90 dB(A) under the helmet for HEMS crew. No occupational hearing
      loss was identified with audiometry. A significant level shift of the Distortion
      Product Otoacoustic Emissions at 4 kHz for HEMS crew compared to MECU physicians
      was found indicating that noise affected the outer hair cell function of the
      inner ear, thus potentially reducing the hearing ability of the HEMS crew.
      DISCUSSION: Further initiatives to prevent noise exposure should be taken, such
      as active noise reduction or custom-made in-ear protection with communication
      system for HEMS personnel. Furthermore, better insulation of MECU and ambulances
      is warranted. CONCLUSION: We found that the exposure levels exceeded the
      recommendations described in the European Regulative for Noise, which requires
      further protective initiatives. Although no hearing loss was demonstrated in the
      personnel of the ground-based units, a reduced function of the outer sensory hair
      cells was found in the HEMS group following missions.

PMID- 29208019
TI  - Correlation between quantitative analysis of wall shear stress and intima-media
      thickness in atherosclerosis development in carotid arteries.
AB  - BACKGROUND: This paper presents quantitative analysis of blood flow shear stress
      by measuring the carotid arterial wall shear stress (WSS) and the intima-media
      thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly
      basis in order to cause atherosclerosis. METHODS: This study is based on
      establishing an atherosclerosis model of high-fat rabbits, and measuring the
      rabbits' common carotid arterial WSS of the experimental group and control group
      on a weekly basis. Detailed analysis was performed by using WSS quantification.
      RESULTS: We have demonstrated small significant difference of rabbit carotid
      artery WSS between the experimental group and the control group (P<0.01) from the
      1st week onwards, while the IMT of experimental group had larger differences from
      5th week compared with the control group (P<0.05). Next, we have shown that with
      increasing blood lipids, the rabbit carotid artery shear stress decreases and the
      rabbit carotid artery IMT goes up. The decrease of shear stress appears before
      the start of IMT growth. Furthermore, our receiver operator characteristic (ROC)
      curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm2,
      the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and
      the specificity is 81.3%. The area under the ROC curve is 0.9283. CONCLUSIONS:
      All these data goes to show that WSS decreasing to 1.198 dyne/cm2 can be used as
      an indicator that rabbit common carotid artery comes into the period of fibrous
      plaques. In conclusion, our study is able to find and confirm that the decrease
      of the arterial WSS can predict the occurrence of atherosclerosis earlier, and
      offer help for positive clinical intervention.

PMID- 29208020
TI  - Mapping upper-limb motor performance after stroke - a novel method with utility
      for individualized motor training.
AB  - BACKGROUND: Chronic upper limb motor impairment is a common outcome of stroke.
      Therapeutic training can reduce motor impairment. Recently, a growing interest in
      evaluating motor training provided by robotic assistive devices has emerged.
      Robot-assisted therapy is attractive because it provides a means of increasing
      practice intensity without increasing the workload of physical therapists.
      However, movements practised through robotic assistive devices are commonly pre
      defined and fixed across individuals. More optimal training may result from
      individualizing the selection of the trained movements based on the individual's
      impairment profile. This requires quantitative assessment of the degree of the
      motor impairment prior to training, in relevant movement tasks. However, standard
      clinical measures for profiling motor impairment after stroke are often
      subjective and lack precision. We have developed a novel robot-mediated method
      for systematic and fine-grained mapping (or profiling) of individual performance
      across a wide range of planar arm reaching movements. Here we describe and
      demonstrate this mapping method and its utilization for individualized training.
      We also present a novel principle for the individualized selection of training
      movements based on the performance maps. METHODS AND RESULTS: To demonstrate the
      utility of our method we present examples of 2D performance maps produced from
      the kinetic and kinematics data of two individuals with stroke-related upper limb
      hemiparesis. The maps outline distinct regions of high motor impairment. The
      procedure of map-based selection of training movements and the change in motor
      performance following training is demonstrated for one participant. CONCLUSIONS:
      The performance mapping method is feasible to produce (online or offline). The 2D
      maps are easy to interpret and to be utilized for selecting individual
      performance-based training. Different performance maps can be easily compared
      within and between individuals, which potentially has diagnostic utility.

PMID- 29208021
TI  - Alliance members' roles in collective field-building: an assessment of leadership
      and championship within the Population Health Intervention Research Initiative
      for Canada.
AB  - BACKGROUND: The Population Health Intervention Research Initiative for Canada
      (PHIRIC) is a multi-stakeholder alliance founded in 2006 to advance population
      health intervention research (PHIR). PHIRIC aimed to strengthen Canada's capacity
      to conduct and use such research to inform policy and practice to improve the
      public's health by building PHIR as a field of research. In 2014, an evaluative
      study of PHIRIC at organisational and system levels was conducted, guided by a
      field-building and collaborative action perspective. METHODS: The study involved
      17 qualitative key informant interviews with 21 current and former PHIRIC
      Planning Committee and Working Group members. The interviews examined how
      individuals and organisations were acting as champions and exerting leadership in
      building the field of PHIR. RESULTS: Founding PHIRIC organisational members have
      been championing PHIR at organisational and system levels. While the PHIR field
      has progressed in terms of enhanced funding, legitimacy, profile and capacity,
      some members and organisations faced constraints and challenges acting as leaders
      and champions in their respective environments. Expectations about the future of
      PHIRIC and field-building of PHIR were mixed, where longer-term and founding
      members of PHIRIC expressed more optimism than recent members. All agreed on the
      need for incorporating perspectives of decision-makers into PHIR directions and
      initiatives. CONCLUSIONS: The findings contribute to understanding alliance
      members' roles in leadership and championship for field-building more generally,
      and for population health and PHIR specifically. Building this field requires
      multi-level efforts, collaborative action and distributed leadership to create
      the necessary conditions for PHIRIC members to both benefit from and contribute
      to advancing PHIR as a field. Lessons from this 'made in Canada' model may be of
      interest to other countries regarding the structures needed for PHIR field
      building.

PMID- 29208022
TI  - Role of endoplasmic reticulum stress in the protective effects of PPARbeta/delta
      activation on endothelial dysfunction induced by plasma from patients with lupus.
AB  - BACKGROUND: We tested whether GW0742, a peroxisome proliferator-activated
      receptor beta/delta (PPARbeta/delta) agonist, improves endothelial dysfunction
      induced by plasma from patients with systemic lupus erythematosus (SLE) involving
      the inhibition of endoplasmic reticulum (ER) stress. METHODS: A total of 12 non
      pregnant women with lupus and 5 non-pregnant healthy women (controls)
      participated in the study. Cytokines and double-stranded DNA autoantibodies (anti
      dsDNA) were tested in plasma samples. Endothelial cells, isolated from human
      umbilical cord veins (HUVECs), were used to measure nitric oxide (NO),
      intracellular reactive oxygen species (ROS) production, nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase activity, and ER stress markers. RESULTS:
      Interferon-gamma, interleukin-6, and interleukin-12 levels were significantly
      increased in plasma from patients with SLE with active nephritis (AN), as
      compared to both patients with SLE with inactive nephritis (IN) and the control
      group. The NO production stimulated by both the calcium ionophore A23187 and
      insulin was significantly reduced in HUVECs incubated with plasma from patients
      with AN-SLE as compared with the control group. Plasma from patients with IN-SLE
      did not modify A23187-stimulated NO production. Increased ROS production and
      NADPH oxidase activity were found in HUVECs incubated with plasma from patients
      with AN-SLE, which were suppressed by the ER stress inhibitor 4-PBA and the NADPH
      oxidase inhibitors, apocynin and VAS2870. GW0742 incubation restored the impaired
      NO production, the increased ROS levels, and the increased ER stress markers
      induced by plasma from patients with AN-SLE. These protective effects were
      abolished by the PPARbeta/delta antagonist GSK0660 and by silencing
      PPARbeta/delta. CONCLUSIONS: PPARbeta/delta activation may be an important target
      to control endothelial dysfunction in patients with SLE.

PMID- 29208023
TI  - Comparison of 2002 AECG and 2016 ACR/EULAR classification criteria and added
      value of salivary gland ultrasonography in a patient cohort with suspected
      primary Sjogren's syndrome.
AB  - BACKGROUND: The objective was to evaluate concordance between 2002 American
      European Consensus Group (AECG) and 2016 American College of Rheumatology
      (ACR)/European League Against Rheumatism (EULAR) classification criteria for
      primary Sjogren's syndrome (pSS) and to assess how salivary gland ultrasonography
      (SGUS) might improve the classification of patients. METHODS: Patients with
      suspected pSS underwent a standardised evaluation, including SGUS, at inclusion
      into the single-centre Brittany DIApSS cohort. Agreement between the two criteria
      sets was assessed using Cohen's kappa coefficient. Characteristics of
      discordantly categorised patients were detailed. RESULTS: We prospectively
      included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR
      criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled
      only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria
      set. Concordance was excellent (kappa = 0.92). Compared to patients fulfilling
      both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had
      similar age and symptom duration but lower frequencies of xerophthalmia and
      xerostomia (p < 0.01 for each) and salivary gland dysfunction (p < 0.01); most
      had systemic involvement (91%), including three (27%) with no sicca symptoms; 91%
      had abnormal salivary gland biopsy and 46% anti-Sjogren's-syndrome-related
      antigen A (anti-SSA); 64% were diagnosed with pSS by the physician. SGUS was
      abnormal in 12% of the 165 patients fulfilling no criteria set. Including SGUS
      among the ACR/EULAR criteria increased sensitivity from 87.4% to 91.1% when
      physician diagnosis was the reference standard. CONCLUSIONS: Agreement between
      AECG and ACR/EULAR criteria sets is excellent. ACR/EULAR criteria are slightly
      more sensitive and classified some patients without sicca symptoms as having pSS.
      Including SGUS in the ACR/EULAR criteria may further improve their sensitivity.

PMID- 29208024
TI  - Selection of a suitable reference gene for quantitative gene expression in mouse
      lymph nodes after vaccination.
AB  - BACKGROUND: The quantification of gene expression is an important tool in the
      evaluation of the immune response to vaccines. Reliable reference genes for gene
      expression studies in mouse draining lymph nodes after vaccination have not been
      reported. RESULTS: The utility of seven potential reference genes was
      investigated using commercially available Taq-man primer/probe mixes. Results
      were evaluated with RefFinder, a web-based program including multiple algorithm
      methods such as geNorm, NormFinder, BestKeeper and the comparative delta-Ct.
      Further assessment was done by applying the candidate reference genes in relative
      expression calculations with genes related to the magnitude and longevity of the
      humoral immune responses. The ubiquitin C gene, Ubc, was found to be the most
      reliable reference gene when validated with well-known genes that are expressed
      at relatively low levels after vaccination. The optimal time of sample collection
      varied depending on the function of the target genes. CONCLUSIONS: This study
      identified Ubc as the most reliable reference gene and provides useful
      information for studies examining immunological gene expression in the draining
      lymph nodes after vaccination in mice.

PMID- 29208025
TI  - Change in cardiac output during Trendelenburg maneuver is a reliable predictor of
      fluid responsiveness in patients with acute respiratory distress syndrome in the
      prone position under protective ventilation.
AB  - BACKGROUND: Predicting fluid responsiveness may help to avoid unnecessary fluid
      administration during acute respiratory distress syndrome (ARDS). The aim of this
      study was to evaluate the diagnostic performance of the following methods to
      predict fluid responsiveness in ARDS patients under protective ventilation in the
      prone position: cardiac index variation during a Trendelenburg maneuver, cardiac
      index variation during an end-expiratory occlusion test, and both pulse pressure
      variation and change in pulse pressure variation from baseline during a tidal
      volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. METHODS: This
      study is a prospective single-center study, performed in a medical intensive care
      unit, on ARDS patients with acute circulatory failure in the prone position.
      Patients were studied at baseline, during a 1-min shift to the Trendelenburg
      position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT
      to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed
      present if cardiac index assessed by transpulmonary thermodilution increased by
      at least 15% after fluid administration. RESULTS: There were 33 patients
      included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15
      (45%) were deemed fluid-responsive. The area under the receiver operating
      characteristic (ROC) curve of the pulse contour-derived cardiac index change
      during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90
      (95% CI, 0.80-1.00) and 0.65 (95% CI, 0.46-0.84), respectively. An increase in
      cardiac index >= 8% during the Trendelenburg maneuver enabled diagnosis of fluid
      responsiveness with sensitivity of 87% (95% CI, 67-100), and specificity of 89%
      (95% CI, 72-100). The area under the ROC curve of pulse pressure variation and
      change in pulse pressure variation during the tidal volume challenge were 0.52
      (95% CI, 0.24-0.80) and 0.59 (95% CI, 0.31-0.88), respectively. CONCLUSIONS:
      Change in cardiac index during a Trendelenburg maneuver is a reliable test to
      predict fluid responsiveness in ARDS patients in the prone position, while
      neither change in cardiac index during end-expiratory occlusion, nor pulse
      pressure variation during a VT challenge reached acceptable predictive
      performance to predict fluid responsiveness in this setting. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was
      registered 6 days after inclusion of the first patient.

PMID- 29208026
TI  - Operationalizing mHealth to improve patient care: a qualitative implementation
      science evaluation of the WelTel texting intervention in Canada and Kenya.
AB  - BACKGROUND: Mobile health (mHealth) applications have proliferated across the
      globe with much enthusiasm, although few have reached scale and shown public
      health impact. In this study, we explored how different contextual factors
      influenced the implementation, effectiveness and potential for scale-up of
      WelTel, an easy-to-use and evidence-based mHealth intervention. WelTel uses two
      way SMS communication to improve patient adherence to medication and engagement
      in care, and has been developed and tested in Canada and Kenya. METHODS: We used
      a comparative qualitative case study design, which drew on 32 key informant
      interviews, conducted in 2016, with stakeholders involved in six WelTel projects.
      Our research was guided by the Consolidated Framework for Implementation Research
      (CFIR), a meta-theoretical framework, and our analysis relied on a modified
      approach to grounded theory, which allowed us to compare findings across these
      projects. RESULTS: We found that WelTel had positive influences on the "culture
      of care" at local clinics and hospitals in Canada and Kenya, many of which
      stretched beyond the immediate patient-client relationship to influence wider
      organizational systems. However, these were mediated by clinician norms and
      practices, the availability of local champion staff, the receptivity and capacity
      of local management, and the particular characteristics of the technology
      platform, including the ability for adaptation and co-design. We also found that
      scale-up was influenced by different forms of data and evidence, which played
      important roles in legitimization and partnership building. Even with robust
      research evidence, scale-up was viewed as a precarious and uncertain process,
      embedded within the wider politics and financing of Canadian and Kenyan health
      systems. Challenges included juggling different interests, determining
      appropriate financing pathways, maintaining network growth, and "packaging" the
      intervention for impact and relevance. CONCLUSIONS: Our comparative case study,
      of a unique transnational mobile health research network, revealed that moving
      from mHealth pilots to scale is a difficult, context-specific process that
      couples social and technological innovation. Fostering new organizational
      partnerships and ways of learning are paramount, as mHealth platforms straddle
      the world of research, industry and public health. Partnerships need to avoid the
      perils of the technological fix, and engage the structural barriers that mediate
      people's health and access to services.

PMID- 29208027
TI  - Animations designed to raise patient awareness of prudent antibiotic use: patient
      recall of key messages and their immediate effect on patient attitude.
AB  - OBJECTIVES: This study aimed to determine if patients recalled key messages from
      antibiotic animations shown on digital displays in General Practice waiting
      rooms, and if watching them changed patients' immediate intentions to consult
      their GP for upper respiratory tract infections, seek antibiotics and self-care.
      RESULTS: The pre intervention focus group found the animations intergenerational,
      informative and educational. 3119 patients were observed in 3 GP practices during
      project team visits; 145 (4.6%) were observed watching the animations; 132 (91%)
      remembered seeing them; the key messages were retained by 47-55% of patients.
      Significant positive differences were observed for questions related to intended
      antibiotic related behaviours.

PMID- 29208028
TI  - Psychosocial effects of infertility among couples attending St. Michael's
      Hospital, Jachie-Pramso in the Ashanti Region of Ghana.
AB  - OBJECTIVE: Infertility is a life crisis with a wide range of socio-cultural,
      emotional, physical and financial problems. This study sought to determine the
      psychosocial effects of infertility among couples attending St. Michael's
      hospital, Jachie-Pramso. A descriptive study design was adopted using a
      quantitative approach. A simple random technique was used to select 100
      respondents and a structured closed ended questionnaire was administered to
      couples who visited the St. Michaels Hospital at Jachie-Pramso. RESULTS: The
      study has revealed that the social effects of infertility on couples included
      exclusion, verbal and physical abuse, divorce as well as stigma. There is high
      level of despondence among couples who are considered infertile. Reliance on
      family members for emotional support as well as avoidance of sensitive
      conversations was the main coping strategies adopted by the couples to cope with
      their conditions. Infertility has psychological, emotional and social
      consequences on individuals as well as couples. Families should support infertile
      individuals in every way that they can so that they will not be isolated.

PMID- 29208029
TI  - Tissue source determines the differentiation potentials of mesenchymal stem
      cells: a comparative study of human mesenchymal stem cells from bone marrow and
      adipose tissue.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) possess intrinsic regeneration capacity
      as part of the repair process in response to injury, such as fracture or other
      tissue injury. Bone marrow and adipose tissue are the major sources of MSCs.
      However, which cell type is more effective and suitable for cell therapy remains
      to be answered. The intrinsic molecular mechanism supporting the assertion has
      also been lacking. METHODS: Human bone marrow-derived MSCs (BMSCs) and adipose
      tissue-derived MSCs (ATSCs) were isolated from bone marrow and adipose tissue
      obtained after total hip arthroplasty. ATSCs and BMSCs were incubated in standard
      growth medium. Trilineage differentiation including osteogenesis, adipogenesis,
      and chondrogenesis was performed by addition of relevant induction mediums. The
      expression levels of trilineage differentiation marker genes were evaluated by
      quantitative RT-PCR. The methylation status of CpG sites of Runx2, PPARgamma, and
      Sox9 promoters were checked by bisulfite sequencing. In addition, ectopic bone
      formation and calvarial bone critical defect models were used to evaluate the
      bone regeneration ability of ATSCs and BMSCs in vivo. RESULTS: The results showed
      that BMSCs possessed stronger osteogenic and lower adipogenic differentiation
      potentials compared to ATSCs. There was no significant difference in the
      chondrogenic differentiation potential. The CpG sites of Runx2 promoter in BMSCs
      were hypomethylated, while in ATSCs they were hypermethylated. The CpG sites of
      PPARgamma promoter in ATSCs were hypomethylated, while in BMSCs they were
      hypermethylated. The methylation status of Sox9 promoter in BMSCs was only
      slightly lower than that in ATSCs. CONCLUSIONS: The epigenetic memory obtained
      from either bone marrow or adipose tissue favored MSC differentiation along an
      osteoblastic or adipocytic lineage. The methylation status of the main
      transcription factors controlling MSC fate contributes to the differential
      differentiation capacities of different source-derived MSCs.

PMID- 29208030
TI  - Experimental therapeutic assays of Tephrosia vogelii against Leishmania major
      infection in murine model: in vitro and in vivo.
AB  - BACKGROUND: Conventional targeted leishmanicidal chemotherapy has persistently
      remained prohibitive for most economically deprived communities due to costs,
      associated time to accessing health services and duration for successful
      treatment programme. Alternatives are bound to be incorporated in rational
      management of leishmaniasis by choice or default due to accessibility and
      cultural beliefs. Therefore, there is need to rigorously investigate and appraise
      the activity of medicinal compounds that may have anti-leishmanicidal activity
      especially in the context of products that are already being utilized by the
      populations for other ailments but have limited information on their therapeutic
      value and possible cytoxicity. Hence, the study examined both in vivo and in
      vitro response of L. major infection to Tephrosia vogelii extracts in BALB/c mice
      as the mouse model. METHODS: A comparative study design was applied for the in
      vivo and in vitro assays of the extract with Pentostam (GlaxoSmithKline, UK) and
      Amphotericin B [FungizoneTM, X-Gen Pharmaceuticals (US)] as standard drugs.
      RESULTS: In BALB/c mice where the chemotherapeutic extract was administered
      intraperitoneally, there was significantly (p < 0.05) larger reduction in lesion
      size and optimal control of parasite burden than those treated orally. However,
      standard drugs showed better activity. Tephrosia vogelii had 50% inhibitory
      concentration (IC50) and IC90 of 12 and 68.5 MUg/ml respectively, while the
      standard drugs had IC50 and IC90 of 5.5 and 18 MUg/ml for Pentostam and 7.8 and
      25.5 MUg/ml for Amphotericin B in that order. In the amastigote assay, the
      infection rates decreased with increase in chemotherapeutic concentration. The
      multiplication indices for L. major amastigotes in macrophages treated with 200
      ug/ml of the standard drugs and extract were significantly different (p < 0.05).
      200 ug/ml of T. vogelii extract showed a multiplication index of 20.57, 5.65% for
      Amphotericin B and 9.56% for Pentostam. There was also significant difference (p
      < 0.05) in levels of Nitric oxide produced in the macrophages. CONCLUSIONS: The
      findings demonstrated that T. vogelii extract has anti-leishmanial activity and
      further assays should be done to ascertain the active compounds responsible for
      anti-leishmanial activity.

PMID- 29208031
TI  - Lipid-rafts remain stable even after ionizing radiation induced disintegration of
      beta1 integrin containing focal adhesions.
AB  - OBJECTIVE: Adhesion of cells to the extracellular matrix is facilitated by
      integrin receptors. We recently found that a nanoscale organization of plasma
      membrane located integrins containing the beta1 subunit is responsible for an
      enhanced radio-resistance in 3D cultured cells over cells grown in 2D. While
      ionizing radiation is known to have broad effects on the lipid composition of the
      plasma membrane and their organization in lipid-rafts, it is not clear whether
      the effects of ionizing radiation on the nanoscale clustering of integrins is
      lipid-raft dependent. RESULTS: Using single molecule microscopy we can show that
      beta1 integrins colocalize with cholesterol in lipid-rafts. Ionizing radiation,
      as an extrinsic stressor, causes the separation of beta1 integrins from
      cholesterol lipid raft suggesting that the effects of ionizing radiation on the
      clustering of beta1 integrins are lipid-raft independent.

PMID- 29208032
TI  - Junior Rounds: an educational initiative to improve role transitions for junior
      residents.
AB  - OBJECTIVE: At our institution, Morning Report focuses mostly on diagnostic
      reasoning. This makes it a challenge for first-year residents to learn to manage
      common on-call emergencies, such as hyperkalemia. We sought to improve their
      preparedness for the transitions they would encounter: from medical student to
      physician at the beginning of the academic year, and from junior resident to
      senior resident toward the end. In response to feedback, we developed the Junior
      Rounds curriculum: a weekly session focused on the approach to commonly
      encountered on-call emergencies and internal medicine referrals. Anonymous
      surveys were sent to trainees, and iterative analysis of monthly feedback led to
      changes to Junior Rounds. RESULTS: Junior Rounds was implemented from August 2015
      to June 2016. Thirty-nine of 92 possible respondents (44%) completed surveys in
      that period. Most respondents agreed that Junior Rounds met their educational
      needs, was presented at an appropriate level, and was more important to their
      learning than other available educational activities. Our experience demonstrates
      that dedicated time for level-specific learning aimed to support the transitions
      of junior residents can be successfully achieved. Iterative adjustment to these
      rounds based on feedback allowed for evolution of the curriculum to meet the
      changing priorities of junior learners.

PMID- 29208034
TI  - Optimal database combinations for literature searches in systematic reviews: a
      prospective exploratory study.
AB  - BACKGROUND: Within systematic reviews, when searching for relevant references, it
      is advisable to use multiple databases. However, searching databases is laborious
      and time-consuming, as syntax of search strategies are database specific. We
      aimed to determine the optimal combination of databases needed to conduct
      efficient searches in systematic reviews and whether the current practice in
      published reviews is appropriate. While previous studies determined the coverage
      of databases, we analyzed the actual retrieval from the original searches for
      systematic reviews. METHODS: Since May 2013, the first author prospectively
      recorded results from systematic review searches that he performed at his
      institution. PubMed was used to identify systematic reviews published using our
      search strategy results. For each published systematic review, we extracted the
      references of the included studies. Using the prospectively recorded results and
      the studies included in the publications, we calculated recall, precision, and
      number needed to read for single databases and databases in combination. We
      assessed the frequency at which databases and combinations would achieve varying
      levels of recall (i.e., 95%). For a sample of 200 recently published systematic
      reviews, we calculated how many had used enough databases to ensure 95% recall.
      RESULTS: A total of 58 published systematic reviews were included, totaling 1746
      relevant references identified by our database searches, while 84 included
      references had been retrieved by other search methods. Sixteen percent of the
      included references (291 articles) were only found in a single database; Embase
      produced the most unique references (n = 132). The combination of Embase,
      MEDLINE, Web of Science Core Collection, and Google Scholar performed best,
      achieving an overall recall of 98.3 and 100% recall in 72% of systematic reviews.
      We estimate that 60% of published systematic reviews do not retrieve 95% of all
      available relevant references as many fail to search important databases. Other
      specialized databases, such as CINAHL or PsycINFO, add unique references to some
      reviews where the topic of the review is related to the focus of the database.
      CONCLUSIONS: Optimal searches in systematic reviews should search at least
      Embase, MEDLINE, Web of Science, and Google Scholar as a minimum requirement to
      guarantee adequate and efficient coverage.

PMID- 29208033
TI  - Evaluating the oxysterol combination of 22(S)-hydroxycholesterol and 20(S)
      hydroxycholesterol in periodontal regeneration using periodontal ligament stem
      cells and alveolar bone healing models.
AB  - BACKGROUND: Oxysterols, oxygenated by-products of cholesterol biosynthesis, play
      roles in various physiological and pathological systems. However, the effects of
      oxysterols on periodontal regeneration are unknown. This study investigated the
      effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and
      20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in
      vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar
      bone defect. METHODS: To evaluate the effects of the combined oxysterols on PDLSC
      biology, we studied the SS-induced osteogenic differentiation of PDLSCs by
      assessing alkaline phosphatase activity, intracellular calcium levels [Ca2+]i,
      matrix mineralization, and osteogenic marker mRNA expression and protein levels.
      To verify the effect of oxysterols on alveolar bone regeneration, we employed
      tooth extraction bone defect models. RESULTS: Oxysterols increased the osteogenic
      activity of PDLSCs compared with the control group. The expression of liver X
      receptor (LXR) alpha and beta, the nuclear receptors for oxysterols, and their
      target gene, ATP-binding cassette transporter A1 (ABCA1), increased significantly
      during osteogenesis. Oxysterols also increased protein levels of the hedgehog
      (Hh) receptor Smo and the transcription factor Gli1. We further confirmed the
      reciprocal reaction between the LXRs and Hh signaling. Transfection of both
      LXRalpha and LXRbeta siRNAs decreased Smo and Gli1 protein levels. In contrast,
      the inhibition of Hh signaling attenuated the LXRalpha and LXRbeta protein
      levels. Subsequently, SS-induced osteogenic activity of PDLSCs was suppressed by
      the inhibition of LXRs or Hh signaling. The application of SS also enhanced bone
      formation in the defect sites of in-vivo models, showing equivalent efficacy to
      recombinant human bone morphogenetic protein-2. CONCLUSIONS: These findings
      suggest that a specific combination of oxysterols promoted periodontal
      regeneration by regulating PDLSC activity and alveolar bone regeneration.

PMID- 29208035
TI  - Prevalence, predictors and adverse outcomes of adolescent pregnancy in sub
      Saharan Africa: a protocol of a systematic review.
AB  - BACKGROUND: Several studies have reported on factors influencing adolescent
      pregnancies and the associated outcomes, but evidence from a systematic review is
      limited, especially in sub-Saharan Africa where the greater burden lies.
      Establishment of accurate epidemiological data on the rates of adolescent
      pregnancy, its predictors, and adverse outcomes (maternal and neonatal) may have
      important implications towards attainment of the Sustainable Development Goals.
      METHODS: This will be a systematic review of studies reporting predictors of
      adolescent pregnancy and adverse outcomes in sub-Saharan Africa published between
      January 2000 and December 2017. The following databases will be searched:
      PubMed/MEDLINE, Excerpta Medica Database (EMBASE), SCOPUS, Popline, Africa Wide
      Information, African Index Medicus, Google scholar and the Cochrane library.
      Three authors will independently screen all potential articles for eligibility as
      guided by the selection criteria. The Stata statistical software will be used in
      analysing the data. Appropriate meta-analytic techniques will be used to pool
      prevalence estimates from studies with similar features, overall and by major
      subgroups as warranted. Heterogeneity of studies will be evaluated by the chi 2
      test on Cochrane's Q statistic. Publication bias will be sorted for using funnel
      plot analysis and Egger's test. Qualitative synthesis will be used where data are
      insufficient to produce a quantitative synthesis. This protocol is reported
      according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      Protocols (PRISMA-P) 2015 guidelines. DISCUSSION: This systematic review and meta
      analysis is expected to serve as a template for designing adolescent-friendly
      preventive and control programmes to help curb the ever-growing burden of
      adolescent pregnancies, and as a guide for future research. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42017070773.

PMID- 29208036
TI  - Informal care and health behaviors among elderly people with chronic diseases.
AB  - BACKGROUND: The mechanism by which social relationships influence health can be
      interpreted as a social network regulating one's health behaviors. Based on the
      hypothesis that relatives, friends, or neighbors are sources of social support
      and may monitor one's health behaviors, researchers have gotten significant and
      consistent results that a social network can regulate health behaviors. However,
      few empirical studies have been conducted to examine the role of informal care in
      the regulation of health behaviors, especially for elderly individuals with
      chronic diseases that can be controlled by healthy behaviors. This paper
      researched the effects of informal care on health behaviors-smoking control,
      dietetic regulation, weight control, and maintenance of exercise-among elderly
      patients with chronic diseases in China who are facing the challenge of aging.
      METHODS: We used the propensity score matching method to control the impacts of a
      very rich set of family and individual characteristics. The 2011-2012 national
      baseline data of the China Health and Retirement Longitudinal Study (CHARLS) was
      used. RESULTS: Our findings showed that informal care could significantly help
      improve the health behaviors of elderly people. Informal care could improve the
      compliance of smoking control and dietetic regulation significantly. Elderly
      people with informal care smoked less and consumed more meals per day. For weight
      control, informal care helped decrease the possibility of weight gain of elderly
      people, but its impacts were not significant for BMI and weight loss. Last, for
      the elders, informal care could only help increase the probability of walking
      exercise; however, there was no significant result for moderate exercise.
      CONCLUSIONS: Findings from this study highlight the importance of informal care
      among elderly people. Our results appeal to policy makers who aim to control
      chronic diseases that they should take informal care into account and provide
      appropriate policies to meet the demand of informal care for elderly people.

PMID- 29208037
TI  - Uterine rupture in a primigravid patient, an uncommon but severe obstetrical
      event: a case report.
AB  - BACKGROUND: A spontaneous rupture of the unscarred uterus in a primigravid
      patient is extremely rare and is associated with high perinatal and maternal
      morbidity and mortality. CASE PRESENTATION: A 34-year-old white primigravid
      woman, 31 + 3 weeks of gestation, presented with pre-eclampsia and developed a
      sudden acute abdomen. An emergency laparotomy was performed and a uterine rupture
      was found as the cause of the event. A stillborn girl was born. CONCLUSION: A
      rupture of the pregnant uterus should always be considered in a pregnant woman
      presenting with abdominal pain, even in a primigravid patient.

PMID- 29208038
TI  - Genetic investigation of XPA gene: high frequency of the c.682C>T mutation in
      Moroccan XP patients with moderate clinical profile.
AB  - OBJECTIVE: Xeroderma pigmentosum (XP) is a genetically and clinically
      heterogeneous disease, associated with an inherited defect in one of eight
      different genes (XPA to XPG and XPV). In addition to the early onset of the skin
      manifestations, the XP group A is marked by the presence of a mild to severe
      neural disorders which appear tardily and worsens with age. In this study, 9
      patients with moderate clinical profile belonging to 6 XP families were recruited
      to determine the XPA mutational spectrum in Morocco, using the direct sequencing
      of the whole coding region of the XPA gene. RESULTS: The genetic investigation of
      the XPA gene showed that 7 from 9 patients were homozygous for the c.682C>T,
      p.Arg228X mutation, while all their investigated family members were
      heterozygous. The frequency of this mutation was estimated to be 83.33% (5/6
      families) .The molecular analysis of the 5 other exons of the XPA gene, showed
      that the 2 negative siblings carried no mutation in the XPA gene. This finding
      suggests that c.682C>T (p.Arg228X) mutation is relatively associated with
      moderate phenotype in XP group A Moroccan families; this result will also
      contribute to improve the molecular diagnosis of XP disease in Moroccan patients.

PMID- 29208039
TI  - Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and
      necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.
AB  - BACKGROUND: Adenocarcinoma of the pancreas is one of the most aggressive cancer
      diseases affecting the human body. Recent research has shown the importance of
      the perioperative phase in disease progression. Particularly during this
      vulnerable phase, substances such as metamizole and paracetamol are given as
      general anesthetics and postoperative analgesics. Therefore, the effects of
      metamizole and paracetamol on tumor progression should be investigated in more
      detail because the extent to which these substances influence the carcinogenesis
      of pancreatic carcinoma is still unclear. This study analyzed the influence of
      metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and
      paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic
      cancer cell lines PaTu 8988t and Panc-1 in vitro. METHODS: Cell proliferation was
      measured by means of the ELISA BrdU assay and the rate of apoptosis by flow
      cytometry using the Annexin V assay. RESULTS: Metamizole and paracetamol
      significantly inhibited cell proliferation in pancreatic cancer cells. After the
      addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced
      after 3 h of incubation but significantly increased after 9 h of incubation.
      CONCLUSION: The oncogenic potential of pancreatic adenocarcinoma is mainly
      characterized by its extreme growth rate. Non-opioid analgesics such as
      metamizole and paracetamol are given as general anesthetics and postoperative
      analgesics. The combination of metamizole or paracetamol with cytotoxic
      therapeutic approaches may achieve synergistic effects. Further studies are
      necessary to identify the underlying mechanisms so that new therapeutic options
      may be developed for the treatment of this aggressive tumor.

PMID- 29208040
TI  - A systematic review of school-based eHealth interventions targeting alcohol use,
      smoking, physical inactivity, diet, sedentary behaviour and sleep among
      adolescents: a review protocol.
AB  - BACKGROUND: Six key behavioural risk factors (risky alcohol use, smoking, poor
      diet, physical inactivity, sedentary behaviour and unhealthy sleep patterns) have
      been identified as strong determinants of chronic disease, such as cardiovascular
      disease, diabetes and cancers. School-based interventions targeting these
      multiple health risk behaviours among adolescents have the potential to halt the
      trajectory towards later disease, whilst online and mobile technology
      interventions offer advantages in terms of student engagement, reach and
      scalability. Despite this, the efficacy of eHealth school-based interventions
      targeting these six health risk behaviours among adolescents has not been
      evaluated. The proposed systematic review aims to address this by determining the
      nature and efficacy of existing eHealth school-based interventions targeting
      multiple health risk behaviours among adolescents. METHODS: A systematic search
      of the MEDLINE, Embase, PsycINFO and Cochrane Library databases will be conducted
      to identify eligible published papers. Eligible studies will be randomised
      controlled trials, including cluster randomised controlled trials, of
      interventions targeting two or more of the following lifestyle risk behaviours:
      alcohol use, smoking, poor diet, physical inactivity, sedentary behaviour and
      sleep. Eligible studies will be those evaluating interventions delivered in a
      secondary school setting among participants 11-18 years of age, via an eHealth
      platform (Internet, computers of mobile technology). Two reviewers will
      independently screen studies for eligibility, extract data and assess the risk of
      bias. Study outcomes will be summarised in a narrative synthesis, and meta
      analyses will be conducted where it is appropriate to combine studies.
      DISCUSSION: It is anticipated that the results from this review will serve to
      inform the development of future eHealth multiple health behaviour interventions
      for adolescents by identifying common characteristics of effective programs and
      highlighting knowledge gaps in the evidence base. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017072163.

PMID- 29208042
TI  - Abnormal placental cord insertion and adverse pregnancy outcomes: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Abnormal placental cord insertion (PCI) includes marginal cord
      insertion (MCI) and velamentous cord insertion (VCI). VCI has been shown to be
      associated with adverse pregnancy outcomes. This systematic review and meta
      analysis aims to determine the association of abnormal PCI and adverse pregnancy
      outcomes. METHODS: Embase, Medline, CINAHL, Scopus, Web of Science,
      ClinicalTrials.gov, and Cochrane Databases were searched in December 2016 (from
      inception to December 2016). The reference lists of eligible studies were
      scrutinized to identify further studies. Potentially eligible studies were
      reviewed by two authors independently using the following inclusion criteria:
      singleton pregnancies, velamentous cord insertion, marginal cord insertion, and
      pregnancy outcomes. Case reports and series were excluded. The methodological
      quality of the included studies was assessed using the Newcastle-Ottawa Scale.
      Outcomes for meta-analysis were dichotomous and results are presented as summary
      risk ratios with 95% confidence intervals. RESULTS: Seventeen studies were
      included in the systematic review, all of which were assessed as good quality.
      Normal PCI and MCI were grouped together as non-VCI and compared with VCI in
      seven studies. Four studies compared MCI, VCI, and normal PCI separately. Two
      other studies compared MCI with normal PCI, and VCI was excluded from their
      analysis. Studies in this systematic review reported an association between
      abnormal PCI, defined differently across studies, with preterm birth, small for
      gestational age (SGA), low birthweight (< 2500 g), emergency cesarean delivery,
      and intrauterine fetal death. Four cohort studies comparing MCI, VCI, and normal
      PCI separately were included in a meta-analysis resulting in a statistically
      significant increased risk of emergency cesarean delivery for VCI (pooled RR
      2.86, 95% CI 1.56-5.22, P = 0.0006) and abnormal PCI (pooled RR 1.77, 95% CI 1.33
      2.36, P < 0.0001) compared to normal PCI. CONCLUSIONS: The available evidence
      suggests an association between abnormal PCI and emergency cesarean delivery.
      However, the number of studies with comparable definitions of abnormal PCI was
      small, limiting the analysis of other adverse pregnancy outcomes, and further
      research is required.

PMID- 29208041
TI  - Metabolomics reveals distinct, antibody-independent, molecular signatures of MS,
      AQP4-antibody and MOG-antibody disease.
AB  - The overlapping clinical features of relapsing remitting multiple sclerosis
      (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder
      (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that
      detection of disease specific serum antibodies is the gold standard in
      diagnostics. However, antibody levels are not prognostic and may become
      undetectable after treatment or during remission. Therefore, there is still a
      need to discover antibody-independent biomarkers. We sought to discover whether
      plasma metabolic profiling could provide biomarkers of these three diseases and
      explore if the metabolic differences are independent of antibody titre. Plasma
      samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were
      analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein
      profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was
      used to identify significant differences in the plasma metabolite concentrations
      and produce models (mathematical algorithms) capable of identifying these
      diseases. In all instances, the models were highly discriminatory, with a
      distinct metabolite pattern identified for each disease. In addition, OPLS-DA
      identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels
      with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by
      decreased levels of scyllo-inositol and small high density lipoprotein particles
      along with an increase in large low density lipoprotein particles relative to
      both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and
      glucose, along with decreased lactate, alanine, and large high density
      lipoproteins while MOG-Ab disease plasma was defined by increases in formate and
      leucine coupled with decreased myo-inositol. Despite overlap in clinical measures
      in these three diseases, the distinct plasma metabolic patterns support their
      distinct serological profiles and confirm that these conditions are indeed
      different at a molecular level. The metabolites identified provide a molecular
      signature of each condition which is independent of antibody titre and EDSS, with
      potential use for disease monitoring and diagnosis.

PMID- 29208043
TI  - Self-sampling for human papillomavirus testing among rural young women of KwaZulu
      Natal, South Africa.
AB  - BACKGROUND: Cervical cancer is a major problem in women and it is important to
      find a suitable and acceptable screening method, especially among young in low
      resource areas for future human papillomavirus (HPV) vaccine follow-up
      investigations. The study sought to test the acceptability of self-sampling as
      well as the suitability of the specimen collecting devices. METHODS: Ninety-eight
      young women from rural KwaZulu-Natal were enrolled between March and July 2014.
      Collected genital specimens were transferred to colour indicator cards for HPV
      detection. Participants answered a questionnaire where they described their
      experiences with self-sampling. Samples were tested for high-risk HPV using
      GP5/6+ PCR. RESULTS: Of the enrolled participants, 91 answered questionnaires and
      indicated that self-sampling was preferred by 51/91 (56%) women while 40/91 (44%)
      indicated preference for sampling by a doctor (p = 0.023). The majority, 64% were
      comfortable using a swab, 22% preferred a brush while 11% were comfortable with
      both devices. Of the 98 self-sampled specimens 61 were negative for HPV in both
      specimens while 37 were HPV-positive in either brush or swab. Of the 37, 26 (70%)
      were HPV-positive in both brush and swab (kappa = 0.743) and 11 (30%) were
      discordant. CONCLUSIONS: Self-sampling was acceptable to the majority of
      participants in this rural area. The Dacron swab was the preferred device, and
      can be used in combination with colour indicator cards for comfortable self
      sampling, easy storage and transport of specimens plus detection.

PMID- 29208044
TI  - An outbreak of acute haemorrhagic conjunctivitis associated with coxsackievirus
      A24 variant in The Gambia, West Africa.
AB  - OBJECTIVE: An outbreak of acute haemorrhagic conjunctivitis occurred in The
      Gambia, West Africa in 2011. Affected individuals presented with conjunctival
      haemorrhages, swelling and ocular discharge. In an effort to identify a causative
      agent of the disease, ocular swabs were taken from patients during the acute and
      convalescent phases. Total RNA was extracted from all samples and reverse
      transcriptase PCR performed using primers specific for all enteroviruses.
      Resulting amplicons were sequenced and data compared to known sequences using the
      BLAST algorithm. RESULTS: Forty-eight swabs were included in the analysis. Of
      these, 21 acute and 9 convalescent swabs (65% of the total) gave positive PCR
      results. Sequence analysis of the resulting amplicons indicated 99% sequence
      identity with coxsackievirus A24 variant identified during independent outbreaks
      of acute haemorrhagic conjunctivitis around the world and suggest the Gambian
      outbreak was due to this virus.

PMID- 29208045
TI  - Joubert's syndrome and related disorders and home-based peritoneal dialysis in
      East Africa: a case report.
AB  - BACKGROUND: Joubert's syndrome is a rare condition affecting an estimated
      1:80,000-1:100,000 individuals. There is underdevelopment of the cerebellar
      vermis resulting in a characteristic molar tooth sign on cross sectional axial
      magnetic resonance imaging. It can occur in association with multi-organ
      involvement; in such cases it is classified as Joubert's syndrome and related
      disorders. To date, there are no cases of Joubert's syndrome and related
      disorders from sub-Saharan Africa described in the literature. CASE PRESENTATION:
      An 8 year old black Kenyan female child was diagnosed in Joubert's syndrome in
      her first year of life. She was noted to have dysmorphic facies and hypotonia in
      the neonatal period and cranial MRI showed dysplasia of the cerebellar vermis and
      typical molar tooth malformation. She was subsequently lost to follow up for
      several years and later presented with anaemia. Further investigation revealed
      bilateral multicystic kidneys and significant renal impairment consistent with a
      diagnosis of end stage renal failure and polycystic kidney disease. She underwent
      home peritoneal dialysis for 7 months. CONCLUSIONS: Joubert's syndrome and
      related disorders is a rare condition. This case report demonstrates that home
      peritoneal dialysis is feasible in a low resource setting. Although it is
      scarcely provided in African countries, it is an effective renal replacement
      strategy for patients with end stage renal disease.

PMID- 29208046
TI  - Short form version of the Quality of Trauma Care Patient-Reported Experience
      Measure (SF QTAC-PREM).
AB  - OBJECTIVE: To enable the valid and reliable measurement of patient experiences we
      previously published a multicenter multi-center validation of the Quality of
      Trauma Care Patient-Reported Experience Measure (QTAC-PREM). The purpose of this
      study was to derive a simplified, short form version of the QTAC-PREM to further
      enhance the feasibility of measuring patient experiences in injury care. To
      identify candidate items for the short form we reviewed the results of the
      original multi-center long form validation cohort study, which included 400
      injury care patients and their family members recruited from three trauma
      centers. We only included the best performing items on the revised short form.
      RESULTS: The acute care component of the measure was shortened by 30% and the
      post-acute care component was shortened by 42%. We identified two subscales on
      the acute measure (information and communication; clinical and ancillary care)
      and one subscale on the post-acute measure (post-discharge information and
      communication). The measurement properties of the short form measure were similar
      to that of the validated long form. This short form assessment of patient injury
      care experiences offers a useful, practical, and easy tool for trauma centers to
      implement for service evaluation, quality improvement, and injury care research.

PMID- 29208047
TI  - Non-conventional dosing of oral anticancer agents in oncology and malignant
      haematology: a systematic review protocol.
AB  - BACKGROUND: Recent advances in cancer therapeutics have resulted in significantly
      improved overall survival and progression-free survival for patients. Targeted
      oral systemic anticancer therapies (SACT) offer a range of treatment approaches
      that differ from traditional cytotoxic chemotherapy: non-cytotoxic oral SACT
      target malignant disease continuously, have less broad and more favourable safety
      profiles, which can improve patients' quality of life (QoL). Toxicities
      associated with daily oral SACT administration can, however, result in non
      adherence and a reduced QoL. Non-conventional dosing of oral SACT, where
      unlicensed doses/schedules of drugs are prescribed, is one approach increasingly
      adopted by clinicians to reduce toxicities and subsequent non-adherence and to
      improve QoL. Guidance governing this practice is, however, limited. This
      systematic review aims to identify evidence about prescribing practices of, and
      outcomes from, non-conventional dosing of oral SACT in oncology and malignant
      haematology. METHODS: A search using the following electronic databases will be
      conducted: Ovid MEDLINE, Ovid EMBASE, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL) and Cochrane Registry of Controlled Trials. Studies
      will be selected based on predefined inclusion/exclusion criteria. Critical
      appraisal will be conducted to identify potential biases, strengths and
      limitations of included studies. Extracted data will be tabulated to sort and
      summarise key findings. An initial literature search indicated that studies
      reporting non-standard dosing of oral SACT intervention studies are diverse and
      heterogeneous in study design. Extracted data will, therefore, be tabulated, and
      together with a narrative synthesis of integrated key findings, will be presented
      and discussed in reference to the strengths and weaknesses of the evidence base.
      If sufficient stratified data is available (e.g. age group, tumour type, disease
      stage) or intervention (drug, dosing schedule), sub-group analysis will be
      conducted to inform prescribing practice. DISCUSSION: This review will identify
      relevant literature on the topic to inform prescribers working in oncology and
      malignant haematology. It will also analyse any evidence of the following
      outcomes: toxicity, treatment adherence and/or QoL outcomes for patients
      receiving non-standard doses of oral SACT. Limitations in the evidence base may
      arise from variability in both the type and quality of studies reviewed.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017076195 .

PMID- 29208048
TI  - Quantifying heterogeneity in individual participant data meta-analysis with
      binary outcomes.
AB  - BACKGROUND: In meta-analyses (MA), effect estimates that are pooled together will
      often be heterogeneous. Determining how substantial heterogeneity is is an
      important aspect of MA. METHOD: We consider how best to quantify heterogeneity in
      the context of individual participant data meta-analysis (IPD-MA) of binary data.
      Both two- and one-stage approaches are evaluated via simulation study. We
      consider conventional I 2 and R 2 statistics estimated via a two-stage approach
      and R 2 estimated via a one-stage approach. We propose a simulation-based
      intraclass correlation coefficient (ICC) adapted from Goldstein et al. to
      estimate the I 2, from the one-stage approach. RESULTS: Results show that when
      there is no effect modification, the estimated I 2 from the two-stage model is
      underestimated, while in the one-stage model, it is overestimated. In the
      presence of effect modification, the estimated I 2 from the one-stage model has
      better performance than that from the two-stage model when the prevalence of the
      outcome is high. The I 2 from the two-stage model is less sensitive to the
      strength of effect modification when the number of studies is large and
      prevalence is low. CONCLUSIONS: The simulation-based I 2 based on a one-stage
      approach has better performance than the conventional I 2 based on a two-stage
      approach when there is strong effect modification with high prevalence.

PMID- 29208049
TI  - Selecting the right gate to identify relevant cells for your assay: a study of
      thioglycollate-elicited peritoneal exudate cells in mice.
AB  - OBJECTIVE: In this study, we investigate the diversity and modulation of
      leukocyte populations represented in the gates defined by size and granularity at
      different time points of thioglycollate-induced peritonitis in mouse. RESULTS:
      The inflammatory cells were distributed into four regions (R1-R4) of a data plot
      graph defined by cell size and granularity. R1 and R2 contained agranular cells
      that were small in size and predominately included T (CD3+) lymphocytes along
      with B (B220+) lymphocytes. Macrophages (F4/80+) were the predominant cells found
      in the R3 region. However, these cells were present in all regions, albeit at a
      lower frequency in R1 and R2. Granulocytes (Gr1+) were mainly distributed in R3
      and R4. The wide distribution of F4/80+ and Gr1+ cells may reflect the
      recruitment and activation state of the different macrophage and granulocyte
      populations. Based on these observations, size and granularity may contribute to
      an initial step in the analysis and sorting of thioglycollate-elicited peritoneal
      exudate cells. However, the developmental stage and cell activation state may
      interfere with cell segregation using size and granularity as parameters.

PMID- 29208051
TI  - A novel mutation in ST14 at a functionally significant amino acid residue expands
      the spectrum of ichthyosis-hypotrichosis syndrome.
AB  - BACKGROUND: Mutations in the ST14 gene, encoding the serine protease matriptase,
      have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian
      disorder with skin and hair manifestations which include, in addition to
      ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However,
      the understanding of the specific consequences of mutations in ST14 on the
      development of this syndrome is incomplete. RESULTS: Using a targeted next
      generation sequencing array of 38 ichthyosis-associated genes on a large cohort
      of 180 ichthyosis patients from a primarily consanguineous background, a
      previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a
      patient with IHS. This mutation affects an essential site within a ligand-binding
      domain of matriptase. Comparison with previous reports of IHS allowed further
      delineation of the phenotype of IHS in correlation with mutations present in
      these patients. Histological and ultrastructural analysis of skin and hair
      identified novel features in this disorder. CONCLUSIONS: This study correlates
      genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum
      of pathology associated with the disorder, and provides clinical evidence of the
      importance of the Asp482 amino acid, previously shown to have an essential role
      in matriptase activation.

PMID- 29208050
TI  - Robotic-assisted total mesorectal excision with the single-docking technique for
      patients with rectal cancer.
AB  - BACKGROUND: The robotic system has advantages of high-definition three
      dimensional vision and articular instruments with high dexterity, allowing more
      precise dissection in the deep and narrow pelvic cavity. METHODS: We enrolled 95
      patients with stage I-III rectal cancer (adenocarcinoma) who underwent totally
      robotic-assisted total mesorectal excision (TME) with single-docking technique at
      a single institution between September 2013 and December 2016. RESULTS: Of the 95
      patients, 48 (50.5%) and 30 (31.6%) patients had lower and middle rectal cancers,
      respectively. Of the 75 (78.9%) patients undergoing preoperative concurrent
      chemoradiotherapy (CCRT), 27 (28.4%) exhibited pathologic complete response
      (pCR). Only four (4.2%) patients underwent abdominoperineal resection and the
      sphincter preservation rate was 95.8%. R0 resection was performed in 92 (96.8%)
      patients. Circumferential resection margin (CRM) and distal resection margin
      (DRM) were positive in 2 (2.1%) and 1 (1.1%) patients, respectively. The
      anastomotic leakage rate was 5.4% (5/95 patients). The overall complication rate
      was 17.9% (17/95 patients); most of them were mild. No 30-day hospital mortality
      occurred, and no patients required conversion to open surgery. In 92 patients
      undergoing R0 resection, 2-year overall survival was 94% and 2-year disease-free
      survival was 83%. CONCLUSIONS: The results demonstrated that totally robotic
      assisted TME with the single-docking technique is safe and feasible for patients
      with rectal cancer, with or without preoperative CCRT. Moreover, favorable pCR
      rate, R0 resection rate, CRM, DRM, sphincter preservation rate, and short-term
      oncological outcomes can be achieved by combining this approach with appropriate
      preoperative CCRT.

PMID- 29208053
TI  - A comparison of the effects of electronic reminders and group bonuses on the
      recording of diagnoses in primary care: a longitudinal follow-up study.
AB  - OBJECTIVE: To improve the recording of diagnoses in visits to general
      practitioners, an observational retrospective study based on a before-after
      design was performed by installing an electronic reminder in the computerized
      patient chart system, reinforced in feedback delivered in superior-subordinate or
      development discussions with the general practitioners. The monthly rate of
      recording diagnoses was observed before and after the intervention. The effect of
      this intervention on recording of diagnoses was compared with the effects of
      financial group bonuses on the same parameter in a neighbouring city. RESULTS:
      Before intervention, the level of recording diagnoses was about 45% in the
      primary care units. Nine months after this intervention there was not yet any
      statistically significant increase in recording of diagnoses but after 21 months
      it yielded a recording rate of 90% (P < 0.001). In three years, this percentage
      reached level over 95%. Group bonuses, a financial incentive serving as a control
      intervention, increased this parameter from 50 to 80% (P < 0.001) in nine months,
      and in 21 months the level of recording diagnoses was 90%. The both methods
      increased the level of recording diagnoses at the same level. Group bonuses acted
      faster but were also more expensive.

PMID- 29208054
TI  - Unpublished systematic reviews and financial support: a meta-epidemiological
      study.
AB  - OBJECTIVE: PROSPERO, an international prospective register of systematic reviews,
      was launched in February 2011 to reduce publication bias of systematic reviews
      (SRs). A questionnaire survey of SR researchers conducted in 2005 indicated the
      existence of unpublished SRs and the potential influence of lack of funding as a
      reason for non-publication. Here, we investigated the publication status of
      registered SRs in the 1st year that PROSPERO launched and assessed the
      association between publication and the existence of funding or conflicts of
      interest (COIs). RESULTS: We identified 326 SRs registered in PROSPERO from
      February 2011 through February 2012. Among them, 85 SRs (26%) remained
      unpublished at least 65 months after registration. We found 241 published
      reports, including four conference abstracts and one poster presentation. Median
      time to publication from protocol registration was 16.3 months. Funding for SRs
      was associated with publication [odds ratio (OR) = 2.10; 95% confidence interval
      (CI) = 1.26 to 3.50]. We found no significant association of author-reported COIs
      with publication (OR = 2.35; 95% CI = 0.67 to 8.20). Twenty SRs were not
      published despite the authors reporting completion of the reviews in PROSPERO.

PMID- 29208055
TI  - Combinations of SNP genotypes from the Wellcome Trust Case Control Study of
      bipolar patients.
AB  - OBJECTIVES: Combinations of genetic variants are the basis for polygenic
      disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs
      in The Wellcome Trust Case Control Study of bipolar patients. METHODS: Parallel
      computing by graphics processing units, cloud computing, and data mining tools
      were used to scan The Wellcome Trust data set for combinations. RESULTS: Two
      clusters of combinations were significantly associated with bipolar disorder. One
      cluster contained 68 combinations, each of which included five SNP genotypes. Of
      the 1998 patients, 305 had combinations from this cluster in their genome, but
      none of the 1500 controls had any of these combinations in their genome. The
      other cluster contained six combinations, each of which included five SNP
      genotypes. Of the 1998 patients, 515 had combinations from the cluster in their
      genome, but none of the 1500 controls had any of these combinations in their
      genome. CONCLUSION: Clusters of combinations of genetic variants can be
      considered general risk factors for polygenic disorders, whereas accumulation of
      combinations from the clusters in the genome of a patient can be considered a
      personal risk factor.

PMID- 29208057
TI  - Caenorhabditis elegans: nature and nurture gift to nematode parasitologists.
AB  - The free-living nematode Caenorhabditis elegans is the simplest animal model
      organism to work with. Substantial knowledge and tools have accumulated over 50
      years of C. elegans research. The use of C. elegans relating to parasitic
      nematodes from a basic biology standpoint or an applied perspective has increased
      in recent years. The wealth of information gained on the model organism, the use
      of the powerful approaches and technologies that have advanced C. elegans
      research to parasitic nematodes and the enormous success of the omics fields have
      contributed to bridge the divide between C. elegans and parasite nematode
      researchers. We review key fields, such as genomics, drug discovery and genetics,
      where C. elegans and nematode parasite research have convened. We advocate the
      use of C. elegans as a model to study helminth metabolism, a neglected area ready
      to advance. How emerging technologies being used in C. elegans can pave the way
      for parasitic nematode research is discussed.

PMID- 29208056
TI  - Importation, Mitigation, and Genomic Epidemiology of Candida auris at a Large
      Teaching Hospital.
AB  - OBJECTIVE Candida auris (CA) is an emerging multidrug-resistant pathogen
      associated with increased mortality. The environment may play a role, but
      transmission dynamics remain poorly understood. We sought to limit environmental
      and patient CA contamination following a sustained unsuspected exposure. DESIGN
      Quasi-experimental observation. SETTING A 528-bed teaching hospital. PATIENTS The
      index case patient and 17 collocated ward mates. INTERVENTION Immediately after
      confirmation of CA in the bloodstream and urine of a patient admitted 6 days
      previously, active surveillance, enhanced transmission-based precautions,
      environmental cleaning with peracetic acid-hydrogen peroxide and ultraviolet
      light, and patient relocation were undertaken. Pre-existing agreements and
      foundational relationships among internal multidisciplinary teams and external
      partners were leveraged to bolster detection and mitigation efforts and to
      provide genomic epidemiology. RESULTS Candida auris was isolated from 3 of 132
      surface samples on days 8, 9, and 15 of ward occupancy, and from no patient
      samples (0 of 48). Environmental and patient isolates were genetically identical
      (4-8 single-nucleotide polymorphisms [SNPs]) and most closely related to the 2013
      India CA-6684 strain (~200 SNPs), supporting the epidemiological hypothesis that
      the source of environmental contamination was the index case patient, who
      probably acquired the South Asian strain from another New York hospital. All
      isolates contained a mutation associated with azole resistance (K163R) found in
      the India 2105 VPCI strain but not in CA-6684. The index patient remained
      colonized until death. No surfaces were CA-positive 1 month later. CONCLUSION
      Compared to previous descriptions, CA dissemination was minimal. Immediate access
      to rapid CA diagnostics facilitates early containment strategies and outbreak
      investigations. Infect Control Hosp Epidemiol 2018;39:53-57.

PMID- 29208052
TI  - Collaborative modeling of an implementation strategy: a case study to integrate
      health promotion in primary and community care.
AB  - BACKGROUND: Evidence-based interventions are more likely to be adopted if
      practitioners collaborate with researchers to develop an implementation strategy.
      This paper describes the steps to plan and execute a strategy, including the
      development of structure and supports needed for implementing proven health
      promotion interventions in primary and community care. RESULTS: Between 10 and 13
      discussion and consensus sessions were performed in four highly-motivated primary
      health care centers involving 80% of the primary care staff and 21 community
      based organizations. All four centers chose to address physical activity, diet,
      and smoking. They selected the 5 A's evidence-based clinical intervention to be
      adapted to the context of the health centers. The planned implementation strategy
      worked at multiple levels: bottom-up primary care organizational change, top-down
      support from managers, community involvement, and the development of innovative e
      health information and communication tools. Shared decision making and practice
      facilitation were perceived as the most positive aspects of the collaborative
      modeling process, which took more time than expected, especially the development
      of the new e-health tools integrated into electronic health records. CONCLUSIONS:
      Collaborative modeling of an implementation strategy for the integration of
      health promotion in primary and community care was feasible in motivated centers.
      However, it was difficult, being hindered by the heavy workload in primary care
      and generating uncertainty inherent to a bottom-up decision making processes.
      Lessons from this experience could be useful in diverse settings and for other
      clinical interventions. Two companion papers report the evaluation of its
      feasibility and assess quantitatively and qualitatively the implementation
      process.

PMID- 29208059
TI  - Associations of the serum long-chain n-3 PUFA and hair mercury with resting heart
      rate, peak heart rate during exercise and heart rate recovery after exercise in
      middle-aged men.
AB  - Long-chain n-3 PUFA from fish have been associated with lower risk of CVD. Fish
      may also contain methylmercury, which may attenuate the inverse associations of
      the long-chain n-3 PUFA. However, the mechanisms underlying these associations
      are not fully known. We evaluated the associations of the serum long-chain n-3
      PUFA (EPA, DPA and DHA) and hair Hg with resting heart rate (HR), peak HR during
      cycle ergometer exercise and HR recovery after exercise. A total of 1008 men from
      the population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60
      years and free of CVD, were studied. After multivariate-adjustments in ANCOVA,
      higher serum total long-chain n-3 PUFA concentration was associated with lower
      resting HR (extreme-quartile difference 2.2 beats/min; 95 % CI 0.2, 4.1, P trend
      across quartiles=0.02), but not with peak HR or HR recovery. Associations were
      generally similar when EPA, DPA and DHA were evaluated individually, except for
      DPA, which was also associated with better HR recovery after exercise (extreme
      quartile difference 2.1 beats/min; 95 % CI 0.1, 4.2, P trend=0.06). Higher hair
      Hg content had a trend towards lower peak HR after adjusting for the long-chain n
      3 PUFA (P trend=0.05), but it only slightly attenuated the associations of the
      serum long-chain n-3 PUFA with HR. These findings suggest that higher serum long
      chain n-3 PUFA concentrations are associated with lower resting HR in middle-aged
      men from Eastern Finland, which may partially explain the potential
      cardioprotective effect of fish intake.

PMID- 29208058
TI  - Low-protein diet supplemented with ketoacids delays the progression of diabetic
      nephropathy by inhibiting oxidative stress in the KKAy mice model.
AB  - Diabetic nephropathy (DN) is a major cause of chronic kidney disease. We aimed to
      investigate the effect of the low-protein diets (LPD) supplemented with ketoacids
      (LPD+KA) in KKAy mice, an early type 2 DN model. KKAy mice were treated with
      normal protein diet (NPD), LPD or LPD+KA from 12 to 24 weeks of age. A period of
      12-week treatment with LPD significantly reduced albuminuria as compared with
      that observed after NPD treatment. Treatment with LPD+KA further reduced
      albuminuria as compared with that observed with LPD treatment alone. Moreover,
      LPD treatment reduced mesangial expansion, thickness of glomerular basement
      membrane and the severity of the podocyte foot process effacement in KKAy mice;
      these effects were more pronounced in KKAy mice treated with LPD+KA. Both LPD and
      LPD+KA treatments slightly reduced total body weight, but had no significant
      effect on kidney weight and blood glucose concentrations when compared with NPD
      treated KKAy mice. LPD treatment slightly attenuated oxidative stress in kidneys
      as compared with that observed in NPD-treated KKAy mice; however, LPD+KA
      treatment remarkably ameliorated oxidative stress in diabetic kidneys as shown by
      decreased malondialdehyde concentrations, protein carbonylation, nitrotyrosine
      expression and increased superoxide dismutase expression. Nutritional therapy
      using LPD+KA confers additional renal benefits as compared with those of LPD
      treatment alone in early type 2 DN through inhibition of oxidative stress.

PMID- 29208060
TI  - Pertussis epidemiology prior to the introduction of a maternal vaccination
      program, Queensland Australia.
AB  - Pertussis morbidity is highest in infants too young to be fully protected by
      routine vaccination schedules. Alternate vaccine strategies are required to
      maximise protection in this age-group. To understand baseline pertussis
      epidemiology prior to the introduction of the maternal pertussis vaccination
      program in 2014, we conducted a retrospective case series analyses of 53 901
      notifications and temporal trends from 1997 to 2014. Notifications were highest
      in infants younger than 4 months of age and highest annual notification rates in
      infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal
      and Torres Strait Islander infants aged younger than 1 month, this rate was
      576/100 000 per year. Notification rates were 40% higher amongst women 15-44
      years, 62.4/100 000 population compared with men (44.5/100 000) and 90% higher in
      Aboriginal and Torres Strait Islander women of the same age (38.2/100 000)
      compared with men (19.7/100 000). Six infant deaths were identified, all younger
      than 2 months of age. Monitoring epidemiology in at-risk groups - infants too
      young to be vaccinated, women of childbearing age and Aboriginal and Torres
      Strait Islander peoples - following implementation of the maternal pertussis
      vaccination program will be important to assess its impact and safety.

PMID- 29208061
TI  - Antichagasic effect of crotalicidin, a cathelicidin-like vipericidin, found in
      Crotalus durissus terrificus rattlesnake's venom gland.
AB  - Cathelicidins are antimicrobial peptides produced by humans and animals in
      response to various pathogenic microbes. Crotalicidin (Ctn), a cathelicidin
      related vipericidin from the South American Crotalus durissus terrificus
      rattlesnake's venom gland, and its fragments have demonstrated antimicrobial and
      antifungal activity, similarly to human cathelicidin LL-37. In order to provide
      templates for the development of modern trypanocidal agents, the present study
      evaluated the antichagasic effect of these four peptides (Ctn, Ctn[1-14], Ctn[15
      34] and LL-37). Herein, Ctn and short derived peptides were tested against the
      epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi Y strain
      (benznidazole-resistant strain) and cytotoxicity in mammalian cells was evaluated
      against LLC-MK2 lineage cells. Ctn inhibited all T. cruzi developmental forms,
      including amastigotes, which is implicated in the burden of infection in the
      chronic phase of Chagas disease. Moreover, Ctn showed a high selective index
      against trypomastigote forms (>200). Ctn induced cell death in T. cruzi through
      necrosis, as determined by flow cytometry analyses with specific molecular probes
      and morphological alterations, such as loss of membrane integrity and cell
      shrinkage, as observed through scanning electron microscopy. Overall, Ctn seems
      to be a promising template for the development of antichagasic agents.

PMID- 29208062
TI  - Performances of statistical methods for the detection of seasonal influenza
      epidemics using a consensus-based gold standard.
AB  - Influenza epidemics are monitored using influenza-like illness (ILI) data
      reported by health-care professionals. Timely detection of the onset of epidemics
      is often performed by applying a statistical method on weekly ILI incidence
      estimates with a large range of methods used worldwide. However, performance
      evaluation and comparison of these algorithms is hindered by: (1) the absence of
      a gold standard regarding influenza epidemic periods and (2) the absence of
      consensual evaluation criteria. As of now, performance evaluations metrics are
      based only on sensitivity, specificity and timeliness of detection, since
      definitions are not clear for time-repeated measurements such as weekly epidemic
      detection. We aimed to evaluate several epidemic detection methods by comparing
      their alerts to a gold standard determined by international expert consensus. We
      introduced new performance metrics that meet important objective of influenza
      surveillance in temperate countries: to detect accurately the start of the single
      epidemic period each year. Evaluations are presented using ILI incidence in
      France between 1995 and 2011. We found that the two performance metrics defined
      allowed discrimination between epidemic detection methods. In the context of
      performance detection evaluation, other metrics used commonly than the standard
      could better achieve the needs of real-time influenza surveillance.

PMID- 29208063
TI  - Unusually high illness severity and short incubation periods in two foodborne
      outbreaks of Salmonella Heidelberg infections with potential coincident
      Staphylococcus aureus intoxication.
AB  - We describe the investigation of two temporally coincident illness clusters
      involving salmonella and Staphylococcus aureus in two states. Cases were defined
      as gastrointestinal illness following two meal events. Investigators interviewed
      ill persons. Stool, food and environmental samples underwent pathogen testing.
      Alabama: Eighty cases were identified. Median time from meal to illness was 5.8
      h. Salmonella Heidelberg was identified from 27 of 28 stool specimens tested, and
      coagulase-positive S. aureus was isolated from three of 16 ill persons.
      Environmental investigation indicated that food handling deficiencies occurred.
      Colorado: Seven cases were identified. Median time from meal to illness was 4.5
      h. Five persons were hospitalised, four of whom were admitted to the intensive
      care unit. Salmonella Heidelberg was identified in six of seven stool specimens
      and coagulase-positive S. aureus in three of six tested. No single food item was
      implicated in either outbreak. These two outbreaks were linked to infection with
      Salmonella Heidelberg, but additional factors, such as dual aetiology that
      included S. aureus or the dose of salmonella ingested may have contributed to the
      short incubation periods and high illness severity. The outbreaks underscore the
      importance of measures to prevent foodborne illness through appropriate washing,
      handling, preparation and storage of food.

PMID- 29208064
TI  - Sleep indices and eating behaviours in young adults: findings from Project EAT.
AB  - OBJECTIVE: To test the associations between sleep indices and eating behaviours
      in young adults, a group vulnerable to suboptimal sleep. DESIGN: Cross-sectional
      analysis of survey measures of sleep (i.e. time in bed, variability, timing and
      quality) and dietary patterns (i.e. breakfast skipping, eating at fast-food
      restaurants, consumption of sports and energy drinks, and sugar-free, sugar
      sweetened and caffeinated beverages). SETTING: Minneapolis/St. Paul metropolitan
      area of Minnesota (USA). SUBJECTS: A total of 1854 respondents (20-30 years, 55.6
      % female) from the 2008-2009 survey conducted for the third wave of the
      population-based Project EAT (Eating and Activity in Teens and Young Adults)
      study. RESULTS: After adjustment for demographic and behavioural covariates in
      linear regression models, those who went to bed after 00.30 hours consumed 0.3
      more servings of sugar-sweetened beverages per day, consumed 1.7 times more
      energy drinks, skipped breakfast 1.8 more times per week and consumed fast food
      0.3 more times per week compared with those who went to bed before 22.30 hours.
      Reported sleep quality in the lowest (Q1) v. highest (Q3) tertile was associated
      with more intake of energy drinks (Q3 v. Q1, prevalence ratio, 95 % CI: 1.79,
      1.24, 2.34), sports drinks (1.28, 1.00, 1.55) and breakfast skipping (adjusted
      mean, 95 % CI: Q1: 4.03, 3.81, 4.26; Q3: 3.43, 3.17, 3.69). Time in bed and sleep
      variability were associated with few eating behaviours. CONCLUSIONS: Some, but
      not all, sleep indices were related to problematic eating behaviours. Sleep
      habits may be important to address in interventions and policies that target
      improvements in eating patterns and health outcomes.

PMID- 29208065
TI  - Use of Confocal Microscopy to Evaluate Equine Zygote Development After Sperm
      Injection of Oocytes Matured In Vivo or In Vitro.
AB  - Confocal microscopy was used to image stages of equine zygote development, at
      timed intervals, after intracytoplasmic sperm injection (ICSI) of oocytes that
      were matured in vivo or in vitro. After fixation for 4, 6, 8, 12, or 16 h after
      ICSI, zygotes were incubated with alpha/beta tubulin antibodies and human
      anticentromere antibody (CREST/ACA), washed, incubated in secondary antibodies,
      conjugated to either Alexa 488 or Alexa 647, and incubated with 561-Phalloidin
      and Hoechst 33258. An Olympus IX81 spinning disk confocal microscope was used for
      imaging. Data were analyzed using chi 2 and Fisher's exact tests. Minor
      differences in developmental phases were observed for oocytes matured in vivo or
      in vitro. Oocytes formed pronuclei earlier when matured in vivo (67% at 6 h and
      80% at 8 h) than in vitro (13% at 6 and 8 h); 80% of oocytes matured in vitro
      formed pronuclei by 12 h. More (p=0.04) zygotes had atypical phenotypes,
      indicative of a failure of normal zygote development, when oocyte maturation
      occurred in vitro versus in vivo (30 and 11%, respectively). Some potential
      zygotes from oocytes matured in vivo had normal phenotypes, although development
      appeared to be delayed or arrested. Confocal microscopy provided a feasible
      method to assess equine zygote development using limited samples.

PMID- 29208066
TI  - Estimating the likely true changes in rheumatic fever incidence using two data
      sources.
AB  - Acute rheumatic fever (ARF) continues to produce a significant burden of disease
      in New Zealand (NZ) Maori and Pacific peoples. Serious limitations in national
      surveillance data mean that accurate case totals cannot be generated. Given the
      changing epidemiology of ARF in NZ and the major national rheumatic fever
      prevention programme (2012-2017), we updated our previous likely true case number
      estimates using capture-recapture analyses. Aims were to estimate the likely true
      incidence of ARF in NZ and comment on the changing ability to detect cases. Data
      were obtained from national hospitalisation and notification databases. The
      Chapman Estimate partially adjusted for bias. An estimated 2342 likely true new
      cases arose from 1997 to 2015, giving a mean annual incidence of 2.9 per 100 000
      (95% CI 2.5-3.5). Compared with the pre-intervention (2009-2011) baseline
      incidence (3.4 per 100 000, 95% CI 2.9-4.0), the likely true 2015 incidence
      declined 44%. Large gaps in data completeness are slowly closing. During the
      period 2012-2015, 723 cases were identified; 83.8% of notifications were matched
      to hospitalisation data, and 87.2% of hospitalisations matched to notifications.
      Despite this improvement, clinicians need to remain aware of the need to notify
      atypical patients. A possible unintended consequence of the national ARF
      prevention programme is increased misdiagnosis.

PMID- 29208067
TI  - Predicting weight status in Chinese pre-school children: independent and
      interactive effects of caregiver types and feeding styles.
AB  - OBJECTIVE: To investigate caregiver type as a potential moderating effect in the
      relationship between feeding style and weight status among Chinese pre-school
      children. DESIGN: Cross-sectional data collected with the Caregiver's Feeding
      Style Questionnaire (CFSQ), anthropometric data, childcare and sociodemographic
      information. SETTING: Shenyang, China. SUBJECTS: Caregiver-child dyads (n 857).
      RESULTS: After controlling for confounders, authoritarian feeding style was
      associated with a 0.30 lower BMI Z-score. Fathers as primary caregivers were
      related to lower BMI Z-score (beta=-0.66), while grandparents as main caregivers
      were associated with higher BMI Z-score (beta=0.66) after adjusting for
      covariates. Mothers buffered the relationship between authoritarian (beta=0.50,
      95 % CI 0.04, 0.95) or indulgent (beta=-0.60, 95 % CI -1.06, -0.14) feeding
      styles and BMI Z-score. Grandparents strengthened the trend that indulgent
      feeding style was related to higher BMI Z-score (beta=0.54, 95 % CI 0.01, 1.08).
      CONCLUSIONS: The results of independent and interactive effects of specific
      feeding styles and caregiver types had different influences on child BMI Z
      scores. Longitudinal investigations are needed to evaluate the effect of fathers'
      and grandparents' feeding on their children's nutrition and weight status.

PMID- 29208068
TI  - In vitro supplementation with the porcine plasma product, betaGRO(r), stimulates
      activity of porcine fetal myoblasts and neonatal satellite cells in a divergent
      manner.
AB  - Two separate experiments were conducted to evaluate the effect of betaGRO(r)
      supplementation on in vitro porcine fetal myoblasts (PFM) and porcine satellite
      cells (PSC) proliferation, fusion and myotube thickness. The PFM and PSC were
      isolated from the m. longissimus dorsi of day 60 of gestation fetuses and piglets
      within 24 h of birth, respectively. Proliferation assays were conducted as 4*3
      factorial arrangements with time of culture (24, 48, 72, 96 h) and media
      treatment (standard porcine media supplemented with 10% (vol/vol) fetal bovine
      serum (HS); HS without 10% fetal bovine serum (LS); and LS supplemented with 10
      mg/ml betaGRO(r) (BG)) as main effects. Fusion and myotube growth assays were
      conducted as 2*2 factorial designs with serum concentration (HS or LS), and
      betaGRO(r) inclusion (0 or 10 mg/ml) as main effects. There was a treatment*time
      interaction and betaGRO(r)*serum interactions for proliferation, fusion and
      myotube thickness of PFM (P<0.01). At all-time points, HS and BG-PFM had greater
      proliferation rates compared LS (P<0.01). The HS treatment had greater
      proliferation rates than BG (P<0.02) except at 72 h of culture (P=0.44). When
      betaGRO(r) was added to LS media, fusion percentage and myotube thickness
      decreased (P<0.01), while fusion percentage increased (P<0.01) and myotube
      thickness was unaffected (P=0.63) when betaGRO(r) was added to HS media. There
      were treatment*time and betaGRO(r)*serum interactions for proliferation rate and
      fusion rate of PSC, respectively (P<0.01). At all-time points, HS had greater
      proliferation rates than LS and BG (P<0.01), and LS had greater proliferation
      rates than BG (P<0.02). When betaGRO(r) was added to LS and HS media, fusion
      percentage increased for both media types (P<0.01). There was no betaGRO(r)*serum
      interaction (P=0.63) for PSC myotube thickness; however, betaGRO(r) supplemented
      myotubes were thicker (P<0.01) than non-betaGRO(r) supplemented myotubes. These
      two experiments indicate in vitro betaGRO(r) supplementation stimulates divergent
      responses based on the age of cell examined.

PMID- 29208069
TI  - The Delirium Drug Scale is associated to delirium incidence in the emergency
      department.
AB  - : ABSTRACTBackground:The Delirium Drug Scale (DDS) is an evaluation scale
      developed to assess a patient's drug burden for delirium. The primary goal is to
      validate the association between the DDS score and the incidence of delirium.
      METHODS: This study was an observational retrospective cross-sectional chart
      review study in patients aged 75 years and older. It was carried out in three
      emergency departments of a tertiary care university health center. Patients were
      included if a medication list was available. Delirium present upon admission was
      assessed during the first five days of admission. RESULTS: A total of 1,205
      subjects were included in the analysis. The mean age was of 83.4 years, and 62.4%
      were female. The prevalence of delirium was 19.1%. A total of 745 patients (62%)
      were exposed to DDS medication. The relative risk for the low (1-2) and high (>2)
      exposure group according to the DDS score was of 1.26 (CI: 0.95; 1.66) and 2.18
      (CI: 1.61; 2.96) compared to a score of 0. In the multivariate analysis,
      dementia, anxiety, insomnia, history of delirium, infection, and acute kidney
      failure were significantly associated to delirium. When adjusted for confounding
      variables, the DDS score was associated with the incidence of delirium with an
      odd ratio (OR) of 1.29 (CI: 1.16; 1.44). CONCLUSIONS: This study found that DDS
      score was associated with delirium incidence. The association persisted in the
      multivariate analysis adjusted for 26 known risks and precipitating factors for
      delirium.

PMID- 29208070
TI  - Neuropsychological outcomes in CHD beyond childhood: a meta-analysis.
AB  - BACKGROUND: Risk for neurodevelopmental delay in infants and children with CHD is
      well established, but longer-term outcomes are equivocal. A meta-analysis was
      conducted to establish whether cognitive deficits remain beyond childhood - into
      teenage and young adult years. Methods and results A total of 18 unique samples,
      involving adolescents, teenagers, and adults with CHD significant enough to
      require invasive intervention, and sourced through searches of Web of Science,
      MEDLINE, CINAHL Plus, and PsychInfo, met the inclusion criteria. These included
      the use of standardised neuropsychology tests across 10 domains of cognitive
      functioning and the reporting of effect size differences with controls. Reports
      of patients with chromosomal or genetic abnormalities were excluded. Pooled
      effect sizes suggested no significant differences between CHD samples and
      controls in terms of general intellectual ability and verbal reasoning. However,
      small-medium effects sizes were noted (0.33-0.44) and were statistically
      significant within the domains of non-verbal reasoning, processing speed,
      attention, auditory-verbal memory, psychomotor abilities, numeracy, and literacy
      with executive functioning also emerging as significant when one study outlier
      was excluded. We also included quality assurance statistics including Cochran's
      Q, T, and I2 statistics, leave-one-out analyses, and assessment of publication
      bias. These often suggested study variability, possibly related to the
      heterogeneity of diagnostic groups included, and different tests used to measure
      the same construct. CONCLUSIONS: Heterogeneity indicated that moderators affect
      cognitive outcomes in CHD. Nevertheless, deficits across cognitive domains were
      discerned, which are likely to have functional impact and which should inform
      practice with this clinical population.

PMID- 29208071
TI  - Economic policy and the double burden of malnutrition: cross-national
      longitudinal analysis of minimum wage and women's underweight and obesity.
AB  - OBJECTIVE: To examine changes in minimum wage associated with changes in women's
      weight status. DESIGN: Longitudinal study of legislated minimum wage levels (per
      month, purchasing power parity-adjusted, 2011 constant US dollar values) linked
      to anthropometric and sociodemographic data from multiple Demographic and Health
      Surveys (2000-2014). Separate multilevel models estimated associations of a $10
      increase in monthly minimum wage with the rate of change in underweight and
      obesity, conditioning on individual and country confounders. Post-estimation
      analysis computed predicted mean probabilities of being underweight or obese
      associated with higher levels of minimum wage at study start and end. SETTING:
      Twenty-four low-income countries. SUBJECTS: Adult non-pregnant women (n 150 796).
      RESULTS: Higher minimum wages were associated (OR; 95 % CI) with reduced
      underweight in women (0.986; 0.977, 0.995); a decrease that accelerated over time
      (P-interaction=0.025). Increasing minimum wage was associated with higher obesity
      (1.019; 1.008, 1.030), but did not alter the rate of increase in obesity
      prevalence (P-interaction=0.8). A $10 rise in monthly minimum wage was associated
      (prevalence difference; 95 % CI) with an average decrease of about 0.14
      percentage points (-0.14; -0.23, -0.05) for underweight and an increase of about
      0.1 percentage points (0.12; 0.04, 0.20) for obesity. CONCLUSIONS: The present
      longitudinal multi-country study showed that a $10 rise in monthly minimum wage
      significantly accelerated the decline in women's underweight prevalence, but had
      no association with the pace of growth in obesity prevalence. Thus, modest rises
      in minimum wage may be beneficial for addressing the protracted underweight
      problem in poor countries, especially South Asia and parts of Africa.

PMID- 29208072
TI  - Risk-based strategies for surveillance of tuberculosis infection in cattle for
      low-risk areas in England and Scotland.
AB  - Disease surveillance can be made more effective by either improving disease
      detection, providing cost savings, or doing both. Currently, cattle herds in low
      risk areas (LRAs) for bovine tuberculosis (bTB) in England are tested once every
      4 years. In Scotland, the default herd testing frequency is also 4 years, but a
      risk-based system exempts some herds from testing altogether. To extend this
      approach to other areas, a bespoke understanding of at-risk herds and how risk
      based surveillance can affect bTB detection is required. Here, we use a
      generalized linear mixed model to inform a Bayesian probabilistic model of
      freedom from infection and explore risk-based surveillance strategies in LRAs and
      Scotland. Our analyses show that in both areas the primary herd-level risk
      factors for bTB infection are the size of the herd and purchasing cattle from
      high-risk areas of Great Britain and/or Ireland. A risk-based approach can
      improve the current surveillance system by both increasing detection (9% and 7%
      fewer latent infections), and reducing testing burden (6% and 26% fewer animal
      tests) in LRAs and Scotland, respectively. Testing at-risk herds more frequently
      can also improve the level of detection by identifying more infected cases and
      reducing the hidden burden of the disease, and reduce surveillance effort by
      exempting low-risk herds from testing.

PMID- 29208073
TI  - Dallas MegaShelter Medical Operations Response to Hurricane Harvey.
AB  - On August 25, 2017, Hurricane Harvey made landfall near Corpus Christi, Texas.
      The ensuing unprecedented flooding throughout the Texas coastal region affected
      millions of individuals.1 The statewide response in Texas included the sheltering
      of thousands of individuals at considerable distances from their homes. The
      Dallas area established large-scale general population sheltering as the number
      of evacuees to the area began to amass. Historically, the Dallas area is one
      familiar with "mega-sheltering," beginning with the response to Hurricane Katrina
      in 2005.2 Through continued efforts and development, the Dallas area had been
      readying a plan for the largest general population shelter in Texas. (Disaster
      Med Public Health Preparedness. 2017;page 1 of 4).

PMID- 29208076
TI  - Improving diagnostic communication in dementia.
AB  - In many countries around the world, owing to the lack of specialists and
      equipment, delay up to a few years in help-seeking and getting diagnostic
      examinations for dementia is not uncommon (Sayegh and Knight, 2013), and this
      situation is considerably more serious in "atypical dementias" due to the
      challenge they present for differential diagnosis. For instance, a survey in the
      USA showed that misdiagnosis was common in patients with Lewy body dementia who,
      on average, saw at least three physicians over a year's time or more before
      getting the proper diagnosis (Lewy Body Dementia Association, 2010). Furthermore,
      in multiethnic communities, cultural and language barriers between practitioners
      and patients may lead to substantial delay as well (Sayegh and Knight, 2013).

PMID- 29208074
TI  - The impact of implementing a Xpert MTB/RIF algorithm on drug-sensitive pulmonary
      tuberculosis: a retrospective analysis.
AB  - Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with
      tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm.
      This study evaluates pre- and post-implementation trends in diagnostic practices
      for drug-sensitive, pulmonary TB in adults in an operational setting, following
      the introduction of the Xpert-based algorithm. We retrospectively analysed data
      from the national TB database for Greater Tzaneen sub-district, Limpopo Province.
      Trends in a number of cases, diagnosis and outcome and characteristics associated
      with death are reported. A total of 8407 cases were treated from 2008 until 2015,
      with annual cases registered decreasing by 31.7% over that time period (from 1251
      to 855 per year). After implementation of Xpert, 69.9% of cases were diagnosed by
      Xpert, 29.4% clinically, 0.6% by smear microscopy and 0.1% by culture. Cases with
      a recorded microbiological test increased from 76.2% to 96.4%. Cases started on
      treatment without confirmation, but with a negative microbiological test
      increased from 7.1% to 25.7%. Case fatality decreased from 15.0% to 9.8%,
      remaining consistently higher in empirically treated groups, regardless of HIV
      status. Implementation of the algorithm coincided with a reduced number of TB
      cases treated and improved coverage of microbiological testing; however, a
      substantial proportion of cases continued to start treatment empirically.

PMID- 29208075
TI  - Estimating vaccine effectiveness against laboratory-confirmed influenza among
      children and adolescents in Lower Saxony and Saxony-Anhalt, 2012-2016.
AB  - Influenza vaccine effectiveness (VE) has to be estimated anew for every season to
      explore vaccines' protective effect in the population. We report VE estimates
      against laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2) and influenza B
      among children aged 2-17 years, using test-negative design. Pooled data from two
      German federal states' surveillance systems for acute respiratory illness from
      week 40/2012 to 20/2016 was used, yielding a total of 10 627 specimens. Odds
      ratios and 95% confidence intervals (95% CIs) for the association between
      laboratory-confirmed influenza and vaccination status were calculated by
      multivariate logistic regression adjusting for age, sex, illness onset and
      federal state. VE was estimated as 1-Odds Ratio. Overall adjusted VE was 33% (95%
      CI: 24.3-40.7). A strong variation of VE between the seasons and subtypes was
      observed: highest season- and subtype-specific VE of 86.2% (95% CI: 41.3-96.7)
      was found against A(H1N1)pdm09 in 7-17-year-olds in 2015/16. Low estimates of VE
      were observed against A(H3N2) in any season, e.g. 1.5% (95% CI: -39.3-30.3) in
      2014/15. Estimates showed a tendency to higher VE among 7-17-year-old children,
      but differences were not statistically significant. Although our findings are
      common in studies estimating influenza VE, we discussed several explanations for
      observed low VE.

PMID- 29208077
TI  - Response Time Consistency Is an Indicator of Executive Control Rather than Global
      Cognitive Ability.
AB  - OBJECTIVES: Intraindividual variability increases with age, but the relative
      strength of association with cognitive domains is still unclear. The objective of
      this study was to examine the relation between cognitive domains and the shape
      and spread of response time (RT) distributions as indexed by intraindividual
      standard deviation (ISD), and ex-Gaussian parameters (MU, sigma, tau). METHODS:
      Healthy adults (40 young [aged 18-30 years], 40 young-old [aged 65-74 years], and
      41 old-old [aged 75-85 years]) completed neuropsychological testing and a touch
      screen attention task from which ISD and ex-Gaussian parameters were derived. The
      relation between RT performance and cognitive domains (memory, processing speed,
      executive functioning) was examined with structural equation modeling (SEM), and
      the predictive power of RT distribution indices over age was investigated with
      linear regression. RESULTS: ISD, MU, and tau, but not sigma, showed a linear
      increase with age group. An SEM showed that independent of age, tau was most
      strongly associated with executive functioning, while MU exhibited less critical
      associations. Linear regression indicated that MU and tau explained a significant
      portion of variance in processing speed and executive ability in addition to age
      group. Memory was more parsimoniously predicted by age, without any significant
      contribution of ex-Gaussian parameters. CONCLUSIONS: The findings suggest that
      exceptionally slow responses convey attention lapses through wavering of
      cognitive control, which strongly correspond to executive functioning tests.
      General slowing and extremely slow responses predicted processing speed and
      executive performance beyond age group, indicating that RT metrics are sensitive
      to differences in cognitive ability. (JINS, 2018, 24, 456-465).

PMID- 29208078
TI  - Community junior sport sponsorship: an online experiment assessing children's
      responses to unhealthy food v. pro-health sponsorship options.
AB  - OBJECTIVE: To explore children's responses to sponsorship of community junior
      sport by unhealthy food brands and investigate the utility of alternative, pro
      health sponsorship options. DESIGN: Between-subjects experiment, with four
      sponsorship conditions: A, non-food branding (control); B, unhealthy food
      branding; C, healthier food branding; D, obesity prevention campaign branding.
      SETTING: Online experiment conducted in schools. Participants were shown a junior
      sports pack for their favourite sport that contained merchandise with branding
      representing their assigned sponsorship condition. Participants viewed and rated
      the sports pack, completed a distractor task, then completed questions assessing
      brand awareness, brand attitudes and preference for food sponsors' products.
      SUBJECTS: Students in grades 1 to 3 (aged 5-10 years; n 1124) from schools in
      metropolitan Melbourne, Australia. RESULTS: Compared with the control condition,
      there were no significant effects of unhealthy food branding on awareness of,
      attitudes towards or preference for these brands. Exposure to healthier food
      branding prompted a significant increase in the proportion of children aware of
      these brands, but did not impact attitudes towards or preference for these
      brands. Exposure to either healthier food branding or obesity prevention campaign
      branding prompted a significant reduction in the proportion of children showing a
      preference for unhealthy food sponsor products. CONCLUSIONS: The sponsorship of
      children's sport by healthier food brands may promote awareness of these brands
      and healthier sponsorship branding may reduce preferences for some unhealthy food
      products. Establishing and implementing healthy sponsor criteria in sports clubs
      could forge healthier sponsorship arrangements and help phase out unhealthy food
      and beverage sponsors.

PMID- 29208079
TI  - Asthma control, lung function, symptoms, and corticosteroid sparing after
      omalizumab initiation in patients with allergic asthma.
AB  - BACKGROUND: Omalizumab is approved in patients with moderate-to-severe allergic
      asthma with symptoms uncontrolled, despite the mainstay therapy. OBJECTIVE:
      Electronic medical records (EMR) were used to increase the knowledge of
      omalizumab effectiveness in a real-world setting. METHODS: Patients with
      uncontrolled moderate-to-severe allergic asthma, ages >=12 years old, initiated
      on omalizumab (index date), with >=12 months of pre- and postindex data, were
      identified in an EMR data base. An Asthma Control Test score (>=20 is considered
      well controlled), forced expiratory volume in 1 second as a percentage of the
      predicted value (<80% considered below normal), symptoms, and oral corticosteroid
      (OCS) and inhaled corticosteroid (ICS) use were compared in the 12-month post-
      versus the preindex period with univariate generalized estimating equations
      adjusted for repeated measurements. RESULTS: A total of 208 patients (mean +/-
      standard deviation[SD] age, 41 +/- 19 years; 64.9% women; 71.2% white; and with a
      mean +/- SD serum total immunoglobulin E level of 455.4 +/- 644.7 IU/mL) were
      identified. In the post- versus preindex period, the patients were significantly
      more likely to have well-controlled asthma (odds ratio [OR] 1.72 [95% confidence
      interval {CI}, 1.11-2.64]) and less likely to have a lung function value below
      normal (nonsignificant) after omalizumab initiation. The patients experienced
      significantly less coughing (OR 0.66 [95% CI, 0.49-0.91]), shortness of breath
      (OR 0.60 [95% CI, 0.44-0.83]), and wheezing (OR 0.59 [95% CI, 0.43-0.81]), with
      no improvement in chest tightness. A significantly lower likelihood of new OCS
      prescriptions (OR 0.58 [95% CI, 0.41-0.82]) was observed. A lower likelihood of
      new high- and medium-dose ICS prescriptions was nonsignificant. CONCLUSION:
      Omalizumab was associated with beneficial effects on asthma control and symptoms,
      and the likelihood of requiring new OCS prescriptions. An observed trend of
      improved lung function and lower likelihood of requiring high- and medium-dose
      ICS did not reach statistical significance.

PMID- 29208080
TI  - Selective Determination of Diazinon and Chlorpyrifos in the Presence of Their
      Degradation Products: Application to Environmental Samples.
AB  - An accurate, sensitive, and selective HPLC method was developed and validated for
      the determination of diazinon and chlorpyrifos. These pesticides were subjected
      to different stress conditions, such as acidic, alkaline, oxidative, thermal, and
      photolytic hydrolysis. The proposed method used a C18 Eclipse Plus column (100 *
      4.6 mm, 3.5 um) and a mobile phase consisting of acetonitrile-water (70 + 30,
      v/v) in an isocratic separation mode. The flow rate was 1.5 mL/min, with UV
      detection at 247 and 230 nm for diazinon and chlorpyrifos, respectively. The
      proposed method was linear over the range of 0.40-50.00 ug/mL for diazinon and
      0.40-40.00 ug/mL for chlorpyrifos. The proposed method was validated per
      International Conference on Harmonization guidelines and subsequently applied for
      the successful determination of the studied pesticides in bulk form in their
      commercial samples in the presence of their degradation products. The developed
      method was used for the determination of the residues of these pesticides in
      lavender and rosemary leaves that were pretreated with the recommended doses of
      these pesticides.

PMID- 29208081
TI  - The 2003 European heat waves.
AB  - The current issue of Eurosurveillance updates and provides additional context to
      the report in early 2004 of an estimated 22 080 excess deaths in England and
      Wales, France, Italy and Portugal during and immediately after the heat waves of
      the summer of 2003 [1]. While estimates for England and Wales [2], France [3],
      and Portugal [4], are largely unchanged from those reported earlier, to these
      should be added 6595-8648 excess deaths in Spain [5], of which approximately 54%
      or 3574-4687 occurred in August, and 1400-2200 in the Netherlands [6], of which
      an estimated 500 occurred during the heat wave of 31 July-13 August. Data for
      Italy, provided here for the cities of Bologna, Milan, Rome, and Turin, are
      compatible with the earlier estimate that 3134 excess deaths occurred in the 21
      Italian regional capitals during the period 1 June-15 August [1,7]; the Italian
      National Institute of Statistics however, reported an excess of 19 780 deaths
      country-wide during June-September 2003 as compared to 2002 [8]. Reports
      elsewhere indicate that approximately 1250 heat-related deaths occurred in
      Belgium during the summer of 2003 [9], that there were 975 excess deaths during
      June-August in Switzerland [10] and 1410 during the period August 1-24 in Baden
      Wurttemberg, Germany [11]. At this point, it seems reasonable to speculate that
      with evidence of heat wave-associated deaths beyond England and Wales, France,
      Italy, and Portugal, the previously published estimate of 22 080 early August
      excess deaths should be revised upward by at least 50% for all of western Europe,
      and by 100% or more if heat events that occurred during June and July 2003 are
      also taken into account.

PMID- 29208082
TI  - The impact of the summer 2003 heat waves on mortality in four Italian cities.
AB  - This study evaluates the impact of the 2003 heat wave on cause-specific mortality
      and the role of demographic characteristics and socioeconomic conditions that may
      have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome
      and Turin. Daily mortality counts, for the resident population by age, sex and
      cause of death were considered. Daily excess mortality was calculated as the
      difference between the number of deaths observed and the smoothed average. The
      impact of heat on health is measured in terms of maximum apparent temperature.
      The greatest excess in mortality was observed in the north west of Italy (Turin,
      +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were
      the age groups most affected, and when stratifying by sex, the increase in
      mortality seemed to be greater among females. The greatest excess in mortality
      was registered in those with low socioeconomic status in Rome (+17.8%) and in
      those with lower education levels in Turin (+43%). The analysis of cause-specific
      mortality not only confirms results from previous studies of an increase in heat
      related mortality by respiratory and cardiovascular diseases, but also shows a
      significant excess in mortality for diseases of the central nervous system and
      for metabolic/endocrine disorders. Results from 2003 highlight the necessity of
      targeting future prevention programmes at the susceptible sub-groups identified.
      The introduction of warning systems alongside efficient preventive plans and the
      monitoring of mortality during heat waves may represent a valid tool for the
      reduction of heat-related deaths.

PMID- 29208083
TI  - Real or media-mediated outbreak of coxsackie infections in 2002 in Greece?
AB  - The purpose of this study was to provide evidence about the existence of a
      coxsackie B outbreak in Greece in 2002 by comparing data of laboratory confirmed
      coxsackie B recent infections in northern Greece between 1998-2001 with data from
      2002. The infections were confirmed serologically, using the indirect
      immunofluorescence method detecting IgM antibodies for coxsackie B1-B6 viruses.
      Sera from 2701 patients residents of northern Greece who were suspected to be
      suffering from coxsackie B virus infections were examined: 2056 between 1998 and
      2001, and 645 in 2002. The comparison between the results of laboratory confirmed
      cases and data available at the laboratory between the two periods showed that: -
      The total number of patients examined per year was higher in 2002 (645 versus an
      annual average of 514 in 1998-2001). - The proportion of laboratory confirmed
      recent infections was lower in 2002 (27.8% versus 32.7%) and the estimated
      incidence was 0.66/10 000 for 2002 and 0.32-0.84/10 000 for 1998-2001. - The age
      distribution differed: the proportions of cases in children versus cases in
      adults were reversed in 2002 compared with 1998-2001, with a higher proportion
      among children in 2002. The difference between the two periods was statistically
      significant. Children aged 3-5 years were the age group most affected in 2002. -
      Seasonal distribution remained the same for both periods (peaks in spring and
      autumn). In 2002, three fatal cases occurred in April, but no deaths were
      reported in 1998-2001. - The clinical syndromes involved also differed: cases of
      respiratory infections, mainly pneumonia, rose from 5.75% to 24.3% in children in
      2002 and cases of myopericarditis rose in adults from 13% in 1998-2001 to 29.5%
      in 2002. The last finding, combined with the involvement of the media (because of
      the three fatal cases) and the panic in the general public that followed
      suggested that an outbreak had occurred, but we conclude that there was no
      outbreak.

PMID- 29208084
TI  - Late detection of a shigellosis outbreak in a school in Madrid.
AB  - Even though shigellosis in Spain is rare, an indigenous outbreak is occasionally
      detected. We describe an outbreak in a school in Madrid caused by person-to
      person transmission of Shigella sonnei. After the detection of Shigella sonnei in
      a stool sample from a 3 year old girl, an investigation at her school was
      initiated. Questionnaires were distributed to the parents of 520 pupils attending
      the school. A case was defined as a school case if it was the first case in a
      child's household, and as a household case if other members of the household had
      fallen ill first. We identified 88 cases (60 pupils and 28 of their family
      members). The attack rate (AR) was 12% in the school and 32% in the families.
      There was a significant association between higher AR and lower age. The outbreak
      lasted for two months. The length and the shape of the epidemic curve of the 60
      cases in pupils suggests person-to-person transmission. Shigella sonnei isolated
      from 5 different cases were typed by pulsed field gel electrophoresis (PFGE) and
      was found to be an identical strain. The prolonged duration of the outbreak was
      probably due to delayed detection, and stopped as soon as control measures were
      introduced.

PMID- 29208085
TI  - Disseminated and chronic Lyme borreliosis in Norway, 1995 - 2004.
AB  - Lyme borreliosis is the most common tickborne infection in Norway. All clinical
      manifestations of Lyme borreliosis other than erythema migrans are notifiable to
      Folkehelseinstituttet, the Norwegian Institute of Public Health. During the
      period 1995-2004 a total of 1506 cases of disseminated and chronic Lyme
      borreliosis were reported. Serological tests were the basis for laboratory
      diagnosis in almost all cases. The annual numbers of cases showed no clear trend
      over the period, but varied each year between 120 and 253 cases, with the highest
      number of cases reported in 2004. Seventy five per cent of cases with information
      on time of onset were in patients who fell ill during the months of June to
      October. There was marked geographical variation in reported incidence rates,
      with the highest rates reported from coastal counties in southern and central
      Norway. Fifty six per cent of the cases were in males and 44% in females. The
      highest incidence rate was found in children aged between 5 and 9 years.
      Neuroborreliosis was the most common clinical manifestation (71%), followed by
      arthritis/arthralgia (22%) and acrodermatitis chronica atrophicans (5%). Forty
      six per cent of patients were admitted to hospital. Prevention of borreliosis in
      Norway relies on measures to prevent tick bites, such as use of protective
      clothing and insect repellents, and early detection and removal of ticks.
      Antibiotics are generally not recommended for prophylaxis after tick bites in
      Norway.

PMID- 29208086
TI  - Absence of infection in asymptomatic contacts of index SARS case in France.
AB  - The first case of severe acute respiratory syndrome (SARS) in France was
      diagnosed in March 2003. We conducted a serological survey to assess whether or
      not asymptomatic persons who had been in contact with this patient during his
      infectious stage had been infected. They were interviewed and asked to provide a
      blood sample for SARS coronavirus immunoglobulin G antibody testing. Despite the
      likely high infectivity of the SARS patient, no asymptomatic SARS infection was
      found in any of the 37 contacts included. These findings support a SARS case
      definition that is essentially based on clinical and epidemiological assessment,
      should SARS re-emerge.

PMID- 29208087
TI  - Reply to Letter: Outbreaks caused by parvovirus B19.
AB  - We are grateful for the comments provided by Kelly and Leydon, and Bernard J
      Cohen. They seem to share our previously expressed opinion that 'in the context
      of measles and rubella elimination programs, study protocols should include data
      collection procedures and laboratory tests able to confirm or discard the
      diagnosis of B19 infections.' [1]. They have provided a useful commentary with
      relevant information and references.

PMID- 29208088
TI  - Pneumococcal vaccination policy in Europe.
AB  - Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important
      cause of invasive clinical manifestations such as meningitis, septicaemia and
      pneumonia, particularly in young children and the elderly. A 23-valent
      polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent
      conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a
      European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a
      questionnaire was distributed to all 15 EU member states, Switzerland, Norway and
      the 10 accession countries in 2003 to ascertain current pneumococcal vaccination
      policy. Twenty three of the 27 target countries, constituting the current
      European Union (plus Norway and Switzerland), completed the questionnaire. PPV
      was licensed in 22 of the 23 responding countries and was in the official
      recommendations of 21. In all the 20/21 countries for which information was
      available, risk groups at higher risk of infection were targeted. The number of
      risk groups targeted ranged from one to 12. At least 17 countries recommend that
      PPV be administered to all those >65 years of age (in three countries, to those
      over 60 years of age). Thirteen countries had developed national recommendations
      for PCV in 2003. No country recommended mass infant immunisation at that time,
      but rather targeted specific risk groups (between 1 and 11), particularly
      children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to
      children under two years of age in seven countries, and in four countries to
      children under five years of age. Future decisions on use of pneumococcal
      vaccines in Europe will be decided on the basis of several factors including:
      local disease burden; the predicted impact of any universal programme,
      particularly the importance of serotype replacement and herd immunity (indirect
      protection to the unvaccinated population); the effectiveness of reduced dose
      schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since
      implemented a universal infant PCV immunisation policy.

PMID- 29208089
TI  - A human case of travel-related rabies in Austria, September 2004.
AB  - A young male Austrian tourist, aged 23 years and unvaccinated against rabies, was
      bitten by a dog in Morocco in July 2004. One month later he was hospitalised in
      Ceuta with symptoms compatible with rabies. He died on 23 September in an
      Austrian hospital after a diagnosis of rabies was confirmed by FAT, IHC and RT
      PCR (including sequencing) of the neck skin and the RT-PCR (including sequencing)
      of the pharyngeal swab. This Austrian case of laboratory confirmed rabies
      highlights the urgent need for reinforcement of the international recommendations
      for travel vaccinations.

PMID- 29208090
TI  - Mortality in Spain during the heat waves of summer 2003.
AB  - The effect of the elevated temperatures on mortality experienced in Europe during
      the summer of 2003 was observed in several countries. This study, carried out in
      Spain, describes mortality between 1 June and 31 August and evaluates the effect
      of the heat wave on mortality. Observed deaths were obtained from official death
      registers from 50 provincial capitals. Observed deaths were compared with the
      expected number, estimated by applying a Poisson regression model to historical
      mortality series and adjusting for the upward trend and seasonality observed.
      Meteorological information was provided by the Instituto Nacional de Meteorologia
      (National Institute of Meteorology). Spain experienced three heat waves in 2003.
      The total associated excess deaths were 8% (43 212 observed deaths compared with
      40 046 expected deaths). Excess deaths were only observed in those aged 75 years
      and over (15% more deaths than expected for the age group 75 to 84 and 29% for
      those aged 85 or over). This phenomenon (heat-associated excess mortality) is an
      emerging public health problem because of its increasing attributable risk, the
      aging of the Spanish population and its forecasted increasing frequency due to
      global warming. The implementation of alert and response systems based on
      monitoring of climate-related risks, emergency room activity and mortality, and
      strengthening the response capacity of the social and health services should be
      considered.

PMID- 29208091
TI  - Mortality in Portugal associated with the heat wave of August 2003: Early
      estimation of effect, using a rapid method.
AB  - During the first two weeks of August 2003, Portugal was affected by a severe heat
      wave. Following the identification in Portugal of the influence of heat waves on
      mortality in 1981 and 1991 (estimated excess of about 1900 and 1000 deaths
      respectively), the Observatorio Nacional de Saude (ONSA) - Instituto Nacional de
      Saude Dr. Ricardo Jorge, together with the Vigilancia Previsao e Informacao -
      Instituto de Meteorologia, created a surveillance system called ICARO, which has
      been in operation since 1999. ICARO identifies heat waves with potential
      influence on mortality [1]. Before the end of the 2003 heat wave, ONSA had
      produced a preliminary estimate of its effect on mortality. The results based on
      daily number of deaths from 1 June to 12 August 2003 were presented within 4
      working days. Data was gathered from 31 National Civil registrars, covering the
      district capitals of all 18 districts of mainland Portugal, and representing
      approximately 40% of the mainland's mortality. The number of deaths registered in
      the period 30 July to 12 August was compared with the ones registered during 3
      comparison periods: (in July): 1-14 July, 1-28 July, and 15-28 July). 15-28 July,
      the period best resembling the heat wave in time and characteristics, produced an
      estimation of 37.7% higher mortality rate then the value expected under normal
      temperature conditions. From this value, an estimate of 1316 death excess was
      obtained for mainland Portugal. The main purpose of this article is to present
      the method used to identify and assess the occurrence of an effect (excess
      mortality) during the heat wave of summer 2003.

PMID- 29208092
TI  - New diagnoses of HTLV infection in England and Wales: 2002-2004.
AB  - Human T cell lymphotropic viruses (HTLV) are retroviruses transmitted through
      breastfeeding, sexual contact, blood transfusion and injecting drug use. HTLV is
      endemic in the Caribbean, and parts of Africa, Japan and South America, with
      isolated foci in other areas. Infection is life long. Fewer than 5% of those
      infected progress to one of the HTLV-related diseases, but these are debilitating
      and often fatal. In England and Wales, laboratory and clinical reports of new
      HTLV diagnoses are routinely collected, including infections identified by the
      blood service since the introduction of anti-HTLV testing in August 2002. Between
      2002 and 2004, 273 individuals were diagnosed with HTLV: 102 (37%) were male and
      169 female (sex was not reported for two). Median ages at diagnosis were 54 and
      50 years respectively. Clinical reports were received for 78% (212/273)
      individuals. Where reported, 58% (116/199) of individuals were of black Caribbean
      ethnicity and 29% (57/199) white; 87% (128/147) were probably infected
      heterosexually or through mother-to-child transmission; 45% (66/146) were
      probably infected in the Caribbean and 40% (59/146) in the United Kingdom. An
      appreciable number of HTLV infections continue to be diagnosed within England and
      Wales, with increases in 2002-2003 because of anti-HTLV testing of blood
      donations. While most infections diagnosed are directly associated with the
      Caribbean, transmission of HTLV infection is occurring within England and Wales.
      Specialist care services for HTLV-infected individuals and their families have
      improved in recent years, but prevention remains limited.

PMID- 29208093
TI  - Comparison of the European Union Disease Surveillance Networks' websites.
AB  - Currently the surveillance of infectious disease in the European Union (EU) is
      supported by the Basic Surveillance Network (BSN) and other disease specific
      surveillance networks (DSNs). Each network has its own website. The objective of
      the current study was to describe the information presented with public access on
      each website from the perspective of its usefulness for the surveillance of an EU
      member state. The BSN and the DSNs cited in Decision 2003/542/CE were included.
      Each website was reviewed and assessed on the inclusion of characteristics from
      three broad categories: 1) general information, 2) procedures for data collection
      and 3) data presentation. Ten surveillance network websites were reviewed during
      the week of 5 December 2005. At least 80% of the 10 networks included a list of
      participating countries, the contact addresses for the coordinator of the network
      and the participating country gatekeepers and the network's objectives. Only one
      network specified the source and coverage of the data of each country on its
      website, and seven presented the disease case definition. Raw data were shown on
      eight websites and only two networks included presentation of elaborated data for
      the whole of the EU. Four networks included no reports on their websites. The
      periodicity of presentation for both raw data and elaborated data varied greatly
      between networks. The publicly available information on the 10 network websites
      studied was not homogeneous. We recommend that all networks present a basic set
      of characteristics on their websites, including case definitions, procedures used
      for data collection and periodic reports covering elaborated data for the entire
      EU.

PMID- 29208094
TI  - The epidemiology of severe Streptococcus pyogenes associated disease in Europe.
AB  - Several European countries reported outbreaks of severe disease caused by
      Streptococcus pyogenes in the late 1980s. This marked a departure from the
      previous decades, where very few such outbreaks were noted. These changes in
      disease occurrence formed part of a global phenomenon, the reasons for which have
      yet to be explained. Results of surveillance activities for invasive S. pyogenes
      infection within Europe over the past fifteen years identified further increases
      in many countries. However, variations in surveillance methods between countries
      preclude robust comparisons being made, illustrating the need for a unified
      surveillance strategy across Europe. This was finally embodied in the Strep-EURO
      programme, introduced in 2002.

PMID- 29208096
TI  - An outbreak of airborne tularaemia in France, August 2004.
AB  - Fifteen tularaemia cases were identified after a holiday spent at a converted
      mill in the Vendee region in France, between 9 and 12 August 2004. The mill was
      visited, and descriptive, retrospective cohort and environmental investigations
      were conducted. The 39 people who had stayed at the mill between 24 July and 11
      August were asked about symptoms, exposure to food and animals, and leisure
      activities. A case was defined as a person with evidence of fever and a positive
      serology (seroconversion or significant rise in antibody titre, or a single
      titre) = 40. Culture for Francisella tularensis and polymerase chain reaction
      (PCR) diagnosis was carried out for drinking water, firewood, and domestic
      animals at the mill. Fifteen cases of tularaemia (38%) were confirmed. Twelve of
      the cases (80%) had the pulmonary form. None of the patients was admitted to
      hospital. There was a strong association between infection and participation in a
      dinner at the mill on 4 August (p<10-8). One of the three dogs present in the
      dining room was serologically positive for F. tularensis. Results of analysis of
      environmental samples were negative. These investigations confirmed the
      occurrence of a cluster of 15 tularaemia cases, in patients who were infected on
      the evening of 4 August, in a mill in Vend|e, an endemic area for tularaemia. The
      investigations highlight the existence of nonspecific and benign pulmonary forms
      of the illness in France. The pulmonary form of infection in the human cases and
      the positive serology of the dog suggest contamination by inhalation of
      contaminated particles from the dog!-s fur disseminated by the dog shaking
      itself.

PMID- 29208095
TI  - Emerging Salmonella Enteritidis anaerogenic phage type 14b: Outbreak in
      Norwegian, Swedish and Finnish travellers returning from Greece.
AB  - In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet,
      FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in
      Norwegian travellers returning from Greece. An increase in the same uncommon
      phage type was also registered in Sweden and Finland at the same time. Cases of
      S. Enteritidis PT 14b in patients returning from Greece were reported in these
      three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199
      cases). Case-control studies performed in 2001 in Norway and Sweden indicated
      that consumption of chicken was associated with illness. In 2002 and 2003,
      continuing case reports indicated that this uncommon phage type had probably
      become established in the Greek food chain. Tour operators were informed and
      contacts were made with Greek public health authorities. Because place of
      infection is not systematically included in most Salmonella notification systems,
      the S. Enteritidis phage type 14b outbreak reported here may represent only part
      of a larger outbreak among travellers visiting Greece. Infections are often
      reported only in the tourists' home countries and public health authorities in
      the tourist destinations may not be aware of the problem. Further collaboration
      between national institutes of public health in Europe is needed to detect
      outbreaks occurring among tourists.

PMID- 29208097
TI  - Surveillance of antimicrobial resistance of invasive pathogens: the Estonian
      experience.
AB  - The aim of the present study was to evaluate the needs for surveillance of
      invasive Gram-negative pathogens in Estonia. The antimicrobial susceptibility
      data of invasive isolates of Acinetobacter baumannii, Pseudomonas aeruginosa,
      Klebsiella spp, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae
      and enterococci were collected in accordance with EARSS (European Antimicrobial
      Resistance Surveillance System) protocols. Despite the higher rate of Gram
      positive pathogens, their resistance to antimicrobials was low in contrast to the
      elevated resistance established for Gram negative pathogens. The higher
      resistance to antimicrobials was particularly associated with A. baumannii and P.
      aeruginosa. Also, the proportion of extended spectrum betalactamase (ESBL)
      producing strains was 23% among Klebsiella spp. and 3.6% among E. coli. The
      inclusion of invasive Gram negative pathogens in antimicrobial resistance
      surveillance provides useful information concerning local pathogen
      susceptibility, as well as for the empirical treatment of suspected infections.

PMID- 29208098
TI  - An imported case of canine rabies in Aquitaine: Investigation and management of
      the contacts at risk, August 2004-March 2005.
AB  - In August 2004, a case of rabies was diagnosed in a puppy that had been illegally
      imported from Morocco to Bordeaux (France). Because a great number of people and
      animals were thought to have come into contact with the puppy, extensive tracing
      measures were implemented, and an international alert was launched to trace and
      treat the contacts at risk. One hundred and eighty seven people received post
      exposure treatment, eight of whom also received serovaccination, and 57 animals
      known to have been exposed to the puppy were tested. Six months after the death
      of the rabid animal, none of the people treated showed any signs of rabies, nor
      was any secondary animal case reported. The management of this crisis highlights
      the importance of the role of a rapid alert system at European level. Strict
      application of sanitary control regulations is essential for animals introduced
      into EU countries, and all necessary information must be made available to EU
      residents travelling to rabies enzootic areas.

PMID- 29208099
TI  - An outbreak of mumps in Sweden, February-April 2004.
AB  - Between 24 February and 26 April 2004, Vastra Gotaland county in Sweden reported
      42 cases of suspected mumps. A descriptive study of the cases was undertaken. A
      questionnaire was administered by telephone and vaccine effectiveness was
      calculated using the screening method. Seventy four per cent (31/42) of the
      suspected cases were interviewed by telephone. Eight out of the 42 serum samples
      were positive or equivocal for mumps IgM by ELISA. Mumps virus genome was
      identified in 21/42 (50%) saliva samples. Eleven were selected for sequencing and
      all were confirmed to be mumps virus. Cases were predominantly from 2 small
      towns. Eighteen out of 19 cases that developed bilateral swelling could be linked
      to one small town. The median age of interviewed cases was 43 years (range 5 to
      88). Six cases were admitted to hospital, 5 of which were older than 30 years.
      The highest incidence occurred in the 35 to 44 years age group. Vaccine
      effectiveness was estimated to be 65% for 1 dose and 91% for 2 doses. This
      descriptive study shows the increasing age of mumps cases with increasing vaccine
      coverage. Vaccine effectiveness was particularly high for 2 doses. Second-dose
      uptake must be ensured, as primary vaccine failure is well documented in mumps.
      Stronger precautions must be taken to avoid pools of susceptible older
      individuals accumulating due to the increased risk of complications.

PMID- 29208100
TI  - Outbreak of E. coli O157 infection in the south west of the UK: risks from
      streams crossing seaside beaches.
AB  - In August 2004 seven cases of Escherichia coli O157 infection were identified in
      children on holiday in Cornwall, southwest England, all of whom had stayed at
      different sites in the area. Isolates from all seven cases were confirmed as E.
      coli serogroup O157 phage type 21/28. We carried out a case-control study among
      holidaymakers who visited the beach. A standardised questionnaire was
      administered by telephone to parents. They were asked where on the beach the
      children had played, whether they had had contact with the stream that flowed
      across the beach, and about their use of food outlets and sources of food eaten.
      Cases were more likely to have played in the stream than controls (OR [1.72-
      undefined]). The time spent in the stream by cases was twice spent there by
      controls. Cases and controls were equally exposed to other suspected risk
      factors. PFGE profiles for all the cases were indistinguishable. Increased
      numbers of coliforms were found in the stream prior to the outbreak. Cattle were
      found grazing upstream. We suggest that the vehicle of infection for an outbreak
      of acute gastrointestinal illness caused by E. coli O157 was a contaminated
      freshwater stream flowing across a seaside beach. The onset dates were consistent
      with a point source. Heavy rainfall in the days preceding the outbreak might have
      lead to faeces from the cattle potentially contaminated by E. coli O157
      contaminating the stream, thereby leading to the outbreak. Control measures
      included fencing off the part of the stream in which children played, and putting
      up warning signs around the beach.

PMID- 29208101
TI  - Tuberculosis control in Latvia: integrated DOTS and DOTS-plus programmes.
AB  - From 1991 until the end of 1998, the number of patients with tuberculosis in
      Latvia increased 2.5 times with a simultaneous increase of drug resistant and
      multidrug resistant tuberculosis (MDR-TB). Descriptive analysis of different TB
      programme services, activities and strategies including Directly Observed Therapy
      Short-course (DOTS) for tuberculosis and treatment of MDR-TB, were performed.
      Data from the state tuberculosis registry, drug resistance surveillance, and the
      national MDR-TB database were used. The state-funded national tuberculosis
      control programme (NTAP, Nacionala Tuberkulozes Apkarodanas Programma), based on
      WHO recommended DOTS strategy, was introduced in Latvia in 1996. The NTAP
      includes TB control in prisons. Treatment of MDR-TB using second line drugs was
      started in 1997. Cure rates for TB patients increased from 59.5% in 1996 to 77.5%
      in 2003. Between 1996 and 2003, more than 200 patients began MDR-TB treatment
      each year, and the cure rate was between 66% and 73%. Numbers of MDR-TB patients
      were reduced by more than half during this period. Treatment results including
      MDR-TB reached the WHO target, with cure rates 85% of newly diagnosed patients.
      These results demonstrate that MDR-TB treatment and management using the
      individualised treatment approach can be effectively provided within the overall
      TB programme on a national scale, to successfully treat a large number of MDR-TB
      patients. Rapid diagnostic methods combined with early intensified case finding,
      isolation and infection control measures could decrease transmission of TB and
      MDR-TB in hospitals and in the community. Highly important that MDR-TB management
      follows WHO recommendations in order to stop creating drug resistance to first
      and to second line drugs.

PMID- 29208102
TI  - European recommendations for the management of healthcare workers occupationally
      exposed to hepatitis B virus and hepatitis C virus.
AB  - Exposure prevention is the primary strategy to reduce the risk of occupational
      bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made
      aware of the medicolegal and clinical relevance of reporting an exposure, and
      have ready access to expert consultants to receive appropriate counselling,
      treatment and follow-up. Vaccination against hepatitis B virus (HBV), and
      demonstration of immunisation before employment are strongly recommended. HCWs
      with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >10
      mIU/mL are considered as responders. Responders are protected against HBV
      infection: booster doses of vaccine or periodic antibody concentration testing
      are not recommended. Alternative strategies to overcome non-response should be
      adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and
      HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between
      infection (anti-HBs >50 mUI/ml 30 days after 1st vaccination: anamnestic
      response) and false positive results(anti-HBs >10 mUI/ml 30 days after 3rd
      vaccination: primary response); true positive subjects have resistance to re
      infection. and do not need vaccination The management of an occupational exposure
      to HBV differs according to the susceptibility of the exposed HCW and the
      serostatus of the source. When indicated, post-exposure prophylaxis with HBV
      vaccine, hepatitis B immunoglobulin or both must be started as soon as possible
      (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV)
      infection, follow-up management of HCV exposures depends on whether antiviral
      treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline
      and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is
      recommended, perform ALT (amino alanine transferase) activity at baseline and
      monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is
      detected.

PMID- 29208103
TI  - An outbreak of Campylobacter jejuni associated with consumption of chicken,
      Copenhagen, 2005.
AB  - In May/June 2005 an outbreak of diarrhoeal illness occurred among company
      employees in Copenhagen. Cases were reported from seven of eight companies that
      received food from the same catering kitchen. Stool specimens from three patients
      from two companies were positive for Campylobacter jejuni. We performed a
      retrospective cohort study among employees exposed to canteen food in the three
      largest companies to identify the source of the outbreak and to prevent further
      spread. Using self-administered questionnaires we collected information on
      disease, days of canteen food eaten and food items consumed. The catering kitchen
      was inspected and food samples were taken. Questionnaires were returned by
      295/348 (85%) employees. Of 247 employees who ate canteen food, 79 were cases,
      and the attack rate (AR) was 32%. Consuming canteen food on 25 May was associated
      with illness (AR 75/204, RR=3.2, 95%CI 1.3-8.2). Consumption of chicken salad on
      this day, but not other types of food, was associated with illness (AR=43/97,
      RR=2.3, 95%CI 1.3-4.1). Interviews with kitchen staff indicated the likelihood of
      cross-contamination from raw chicken to the chicken salad during storage. This is
      the first recognised major Campylobacter outbreak associated with contaminated
      chicken documented in Denmark. It is plausible that food handling practices
      contributed to transmission, and awareness of safe food handling and storage has
      since been raised among kitchen staff. The low number of positive specimens
      accrued in this outbreak suggests a general underascertainment of adult cases in
      the laboratory reporting system by a factor of 20.

PMID- 29208104
TI  - Two clusters of human infection with influenza A/H5N1 virus in the Republic of
      Azerbaijan, February-March 2006.
AB  - Following the appearance of influenza A/H5 virus infection in several wild and
      domestic bird species in the Republic of Azerbaijan in February 2006, two
      clusters of potential human avian influenza due to A/H5N1 (HAI) cases were
      detected and reported by the Ministry of Health (MoH) to the World Health
      Organization (WHO) Regional Office for Europe during the first two weeks of March
      2006. On 15 March 2006, WHO led an international team, including infection
      control, clinical management, epidemiology, laboratory, and communications
      experts, to support the MoH in investigation and response activities. As a result
      of active surveillance, 22 individuals, including six deaths, were evaluated for
      HAI and associated risk infections in six districts. The investigations revealed
      eight cases with influenza A/H5N1 virus infection confirmed by a WHO
      Collaborating Centre for Influenza and one probable case for which samples were
      not available. The cases were in two unrelated clusters in Salyan (seven
      laboratory confirmed cases, including four deaths) and Tarter districts (one
      confirmed case and one probable case, both fatal). Close contact with and de
      feathering of infected wild swans was considered to be the most plausible source
      of exposure to influenza A/H5N1 virus in the Salyan cluster, although
      difficulties in eliciting information were encountered during the investigation,
      because of the illegality of some of the activities that might have led to the
      exposures (hunting and trading in wild birds and their products). These cases
      constitute the first outbreak worldwide where wild birds were the most likely
      source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of
      resources to contain the spread of influenza A/H5 in the two districts was
      achieved through collaboration between the MoH, WHO and its international
      partners. Control activities were supported by the establishment of a field
      laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect
      influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two
      affected districts made it unlikely that human cases of influenza A/H5N1 virus
      infection remained undetected.

PMID- 29208105
TI  - Community-acquired methicillin-resistant Staphylococcus aureus in Switzerland :
      first surveillance report.
AB  - Methicillin resistant Staphylococcus Aureus (MRSA) infection is an emerging
      community pathogen. Community-acquired MRSA (CA-MRSA) has been associated with
      virulent strains producing Panton-Valentine leukocidin (PVL) and a variety of
      other exotoxins. In Geneva, PVL-producing CA-MRSA was first reported in 2002 and
      a surveillance system based on voluntary reporting was set up.

PMID- 29208106
TI  - A regional outbreak of S. Typhimurium in Denmark and identification of the source
      using MLVA typing.
AB  - In Denmark, as part of the national laboratory-based surveillance system of human
      enteric infections, all S. Typhimurium isolates are currently sub-typed using
      phage typing, antibiogram typing, and pulsed-field gel electrophoresis (PFGE).
      However, the discriminatory ability of PFGE is not always high enough to
      discriminate within certain phage types, and it is not always possible to
      separate unrelated and related isolates. We have therefore applied multiple locus
      variable number of tandem repeats analysis (MLVA) for surveillance typing of S.
      Typhimurium since 2004. In May and June 2005, an outbreak with 26 cases of S.
      Typhimurium infection was identified by MLVA. The isolates were fully sensitive
      and had one of the most frequently occurring Danish phage types (DT12) and PFGE
      types. S. Typhimurium DT12 isolates from routine surveillance of animals and food
      were typed using MLVA and PFGE for comparison with the human isolates. The typing
      results revealed that an isolate from a pig herd and its corresponding
      slaughterhouse located in the same geographic region as the outbreak had the same
      PFGE and MLVA type as the human isolates. In contrast, all other DT12 isolates
      investigated, which had the same PFGE profile, had different MLVA types. The
      conclusion that the pig herd was the source of the human infections was supported
      by patient information, and pork from the herd stopped entering the market on 29
      June. MLVA may contribute significantly to both surveillance and outbreak
      investigations of S. Typhimurium, as without MLVA typing this outbreak would not
      have been found nor its origin traced.

PMID- 29208108
TI  - Salmonella Enteritidis phage type 21 outbreak in Austria, 2005.
AB  - We report an outbreak of gastroenteritis due to Salmonella Enteritidis PT 21
      associated with attending an annual traditional fair in a small Austrian village
      on 4 May 2005. The outbreak lasted from 4 to 8 May. Descriptive and analytical
      epidemiological investigations were conducted in order to determine the extent of
      the outbreak and to identify outbreak risk factors. Of the 115 persons who
      visited the fair, 85 persons fulfilled the criteria of an outbreak case (attack
      rate=73.9%). Stool specimens from 52 patients, including two kitchen staff, were
      tested for salmonella, and 20 specimens were positive for Salmonella Enteritidis
      PT 21. The cohort study revealed mixed salad (which included potatoes) as the
      likely cause of the outbreak (RR: 10.4, 95%CI 2.8 - 39.1; P=<0.001). The
      causative agent of the outbreak was cultured from the stock of eggs used at the
      fair and from all three drag swabs and one barn dust sample collected from the
      responsible egg laying flock. Molecular subtyping by pulsed-field gel
      electrophoresis of genomic DNA after XbaI digestion showed that isolates from
      eggs, from the flock and from humans were indistinguishable. We hypothesise that
      cross contamination from eggs to boiled potatoes occurred in the kitchen area,
      where raw eggs were handled by village residents preparing a traditional Viennese
      egg dressing. Unrefrigerated storage of peeled potatoes may have favoured
      bacterial growth. Eggs from small rural flocks of laying hens kept in a
      traditional 'natural' way should not be assumed to be salmonella-free.

PMID- 29208107
TI  - Meat inspection for Trichinella in pork, horsemeat and game within the EU:
      available technology and its present implementation.
AB  - A new EU directive relating to meat inspection for Trichinella, expected to come
      into force in 2006, imposes important modifications to current legislation.
      Nevertheless, several issues need more attention. Optimisation of methods,
      especially concerning sensitivity and digestibility of the meat to be inspected,
      along with further simplification of the legislation with regard to the number of
      techniques accepted, is recommended to guarantee that all member states of the EU
      will be given tools to perform inspection of consumer meat at the same high
      level. Additionally, there is a need for guidelines and protocols regarding
      optimal proficiency testing procedures.

PMID- 29208109
TI  - European survey of BCG vaccination policies and surveillance in children, 2005.
AB  - In 2005, all 25 EU countries, as well as Andorra, Bulgaria, Norway, Romania and
      Switzerland, participated in a survey on BCG vaccination in children. BCG was
      recommended nationally for children under 12 months in 12 countries, in older
      children in five countries and in children at risk (from origin, contact or
      travel) in 10 countries. Seven countries did not use BCG systematically.
      Revaccination was practised in four countries. In countries with universal
      vaccination, BCG coverage was high (83.0% to 99.8%). TB cases commonly occurred
      in vaccinated children (at least 30%-98% in five countries using universal or
      high-risk approach). Disseminated infection due to BCG was rarely reported in
      recent years (0-1/100 000 vaccinated). There is a wide variation among BCG
      recommendations in Europe, and nearly half the countries surveyed were
      considering revisions, at a time when the European Centre for Disease Prevention
      and Control (ECDC) is advocating for harmonised vaccine strategies. Data on
      monitoring of BCG coverage in target groups is important but often lacking in
      Europe. Information on BCG status and eligibility should be collected routinely
      through TB case notification. The incidence of severe adverse effects of BCG in
      children should be monitored. Given lack of evidence to its efficacy,
      revaccination should be discontinued.

PMID- 29208110
TI  - First general outbreak of Verocytotoxin-producing Escherichia coli O157 in
      Denmark.
AB  - This report describes the first general outbreak of verocytotoxin-producing E.
      coli (VTEC) in Denmark. Twenty five patients, 18 children and seven adults, with
      culture-confirmed VTEC O157:H- infection and indistinguishable pulsed-field gel
      electrophoresis DNA profiles, were identified during a six month period from
      September 2003 to March 2004. The outbreak strain possessed the virulence genes:
      eae, vtx1 and vtx2c. All patients but one presented with diarrhoea; none
      developed haemolytic uraemic syndrome. The outbreak was restricted to Copenhagen
      and surrounding areas. A case-control study including 11 cases and 55 matched
      controls revealed an association between VTEC O157:H- infection and shopping in a
      specific supermarket chain in Copenhagen and surrounding area, matched odds ratio
      (OR): 8.7 (95% confidence interval (CI): 1.1-71). After exclusion of three
      assumed secondary cases, only consumption of a particular kind of organic milk
      from a small dairy was associated with disease OR: 8.7 (95% CI 1.6-48).
      Environmental and microbiological investigations at the suspected dairy did not
      confirm the presence of the outbreak strain, but the outbreak stopped once the
      dairy was closed and thoroughly cleaned.

PMID- 29208111
TI  - Prolonged outbreak of B meningococcal disease in the Seine-Maritime department,
      France, January 2003 to June 2005.
AB  - Between January 2003 and June 2005, an outbreak of meningococcal disease occured
      in the department of Seine-Maritime in northern France. Eighty six cases were
      notified, giving an average annual incidence of 2.7 cases per 100 000
      inhabitants, compared with 1.6 in France. An especially affected area was defined
      as the city of Dieppe and its surrounding area (26 cases, giving an annual
      incidence of 12 cases per 100 000). This outbreak was due to N. meningitidis
      phenotype B:14:P1.7,16 belonging to the clonal complex ST-32/ET-5. Over the 31
      B14:P1.7,16 cases confirmed by phenotyping methods at the national reference
      centre for meningococci (CNR, Centre National de Reference des meningocoques) the
      case-fatality rate (19%) and the proportion of purpura fulminans (42%) were
      especially high. Teenagers aged between 15 and 19 years and children aged 1 to 9
      years were the most affected. In 2003, health authorities put in place enhanced
      epidemiological surveillance and informed practitioners and population about the
      disease. In 2004, the national vaccination advisory board studied the opportunity
      of using a non licensed outer membrane vesicle vaccine developed in Norway which
      may be effective against the B14:P1.7,16 strain. The Ministry of health decided
      in 2006 to offer vaccination with this vaccine to people aged 1 to 19 years in
      Seine- Maritime.

PMID- 29208112
TI  - Tribute to Andrea Infuso.
AB  - This special issue of Eurosurveillance is dedicated to the memory of Andrea
      Infuso, a dear and respected colleague and friend, who died suddenly on 20
      September 2005 at the age of 44. Andrea was actively involved in the preparation
      of this special issue on vaccination and tuberculosis. As EuroTB coordinator
      since 2000, his knowledge of and contacts with all European experts involved in
      tuberculosis surveillance in Europe were very valuable in conceiving this
      thematic issue. The Euroroundup published in this issue, European survey of BCG
      vaccination policies and surveillance in children, 2005, written by Andrea as
      first author, is a posthumous publication.

PMID- 29208113
TI  - Lymphogranuloma venereum emerging in men who have sex with men in Germany.
AB  - A resurgence of lymphogranuloma venereum (LGV) has been observed in several
      European countries. LGV is not a mandatorily notifiable disease in Germany.
      Reports of LGV cases have actively been collected by the Robert Koch-Institut
      since 2004 to describe the outbreak and estimate the extent of the LGV problem in
      Germany. Updates on the LGV outbreak were published in the German national
      epidemiological bulletin. Physicians were asked to send their samples to a
      laboratory for genotyping. A possible case was defined as a person with symptoms
      of proctitis and/or inguinal lymph node swelling and a positive chlamydia
      serology. A probable case had in addition a positive chlamydia rectal or urinary
      PCR test. A case was confirmed if the genotype L1-L3 was identified based on
      sequence analysis of omp1 gene sequences. Since 2003, LGV has been reported in 78
      male patients in Germany. Of these, 61 patients were confirmed as genotype L2.
      Fifty eight out of 78 patients (74%) are known to be men who have sex with men
      (MSM). Fifty five patients (71%) had rectal symptoms and 49 (63%) knew they were
      HIV positive. Sixty two (79%) of the patients were residents of Berlin or
      Hamburg. LGV has emerged in MSM in Germany at the same time as in other European
      countries. It is thought that LGV may become endemic in the MSM community in
      German metropolitan areas, because the number of reported patients with LGV
      continues to increase. The increase in the number of LGV cases and the high HIV
      prevalence in LGV patients are of great public health concern. Clinicians and MSM
      may not be sufficiently aware of the disease, and existing efforts to promote
      awareness and prevention of sexually transmitted infections and HIV need to be
      strengthened.

PMID- 29208114
TI  - Epidemiological and virological assessment of influenza activity in Europe,
      during the 2004-2005 winter.
AB  - The 2004-2005 influenza season in Europe started in late December 2004 and the
      first influenza activity occurred in the west and southwest (Spain, United
      Kingdom and Ireland). Influenza activity then moved gradually east across Europe
      during January and early February 2005, and from late February until late March,
      most movement was south to north. The intensity of clinical influenza activity in
      ten out of 23 countries was higher than during the 2003-2004 season, and lower or
      equal to the 2003-2004 season in the other 13 countries. The highest consultation
      rates were generally observed among children aged 0-14 years. However, the peak
      consultation rates due to influenza-like illness or acute respiratory infection
      were not especially high when compared with historical data. The predominant
      virus strain was influenza A (83% of total detections) of the H3 subtype (85% of
      H-subtyped A viruses), with fewer influenza B (17% of total detections) or A(H1)
      viruses (15 % of H-subtyped A viruses) detected. The vast majority of A(H3)
      viruses were similar to the reference strains A/Wellington/1/2004 (H3N2) and,
      subsequently, A/California/7/2004 (H3N2) that are closely related drift variants
      of the A/Fujian/411/2002 (H3N2) prototype vaccine strain. The B viruses co
      circulated with A viruses during the whole influenza season in 11 out of 24
      countries. Seven of these were located in the northeast of Europe and in these
      countries the proportion of B viruses was higher (range: 31-60%) than in the rest
      of Europe (range: 6-26%). In 13 out of 24 countries the B viruses circulated
      relatively late in the season. About 43% of all antigenically characterised B
      viruses were B/Hong Kong/330/2001-like (B/Victoria/2/87 lineage), a strain that
      is distinguishable from the vaccine influenza B strain, which was a
      B/Yamagata/16/88 lineage virus. Based on the viruses detected worldwide until
      February 2005, the World Health Organization modified the composition of the 2005
      2006 influenza vaccine from the 2004-2005 season vaccine to include a new A(H3N2)
      component: an A/California/7/2004 (H3N2)-like virus.

PMID- 29208115
TI  - Travel-associated legionnaires' disease in Europe: 2004.
AB  - Six hundred and fifty five cases of travel-associated legionnaires' disease with
      onset in 2004 have been reported to the EWGLINET surveillance scheme by 25
      countries. A total of 84.9% of cases were diagnosed by the urinary antigen test,
      and 37 cultures were obtained. Thirty seven deaths were reported, giving a case
      fatality rate of 5.6%. Eighty six new clusters were detected, 45% of which would
      not have been detected without the EWGLINET scheme. Ninety four accommodation
      sites were investigated and the names of four sites were published on the EWGLI
      website. Fifteen sites were associated with additional cases after a report was
      received to say that investigations and control measures had been satisfactorily
      carried out. Further improvements could be made in the data collected on deaths
      due to travel-associated legionnaires' disease, and on the number of samples
      taken for culture throughout Europe.

PMID- 29208116
TI  - Respiratory viruses and influenza-like illness: a survey in the area of Rome,
      winter 2004-2005.
AB  - Limited information is available on the viral aetiology of influenza-like illness
      (ILI) in Southern European countries. Hereby we report the main findings of a
      survey conducted in the area of Rome during the 2004-2005 winter season. ILI
      cases were defined as individuals with fever >37.5 degrees C and at least one
      constitutional symptom and one respiratory symptom, recruited during the survey
      period. Influenza and other respiratory viruses were identified using polymerase
      chain reaction (PCR) on throat swabs. Basic individual information was collected
      through a standard form. Of 173 ILI cases enrolled, 74 tested positive for one
      virus, and two tested positive for two viruses. Overall, 33.5% of the cases were
      positive for influenza viruses, 5.2% for adenoviruses, 3.5% for parainfluenza
      viruses, 1.7% for coronaviruses, and 1.2% for the respiratory syncitial virus.
      The proportion of influenza virus detection was higher in the 'high influenza
      activity' period. The distribution of viral agents varied across age groups,
      influenza viruses being more likely to be detected in younger patients. Viral
      pathogens were identified in less than 50% of ILI cases occurred during a high
      activity influenza season. The detection of other than influenza viruses was
      sporadic, without evidence of large outbreaks due to specific agents.

PMID- 29208117
TI  - A measles outbreak in children under 15 months of age in La Rioja, Spain, 2005
      2006.
AB  - This paper describes a measles outbreak in La Rioja, Spain, which began in
      December 2005 and mainly affected children under 15 months of age who were not
      yet immunised with MMR vaccine. The measles cases were detected by the mandatory
      reporting system, under which laboratories must report every confirmed measles
      case. Cases were classified in accordance with the National Measles Elimination
      Plan: suspected and laboratory-confirmed. In the period 14 December 2005 to 19
      February 2006, 29 suspected cases of measles were investigated, and 18 were
      confirmed. The mean incubation period was 13.8 days (range: 9 to 18). Of the 18
      confirmed cases, only two were in adults. MMR vaccination was recommended for all
      household contacts, as well as for children aged 6 to 14 months who attended the
      daycare centres where the cases had appeared. At these centres, the second dose
      of MMR was administered ahead of schedule for children under three years of age.
      It was recommended that the first dose of MMR vaccine be administered ahead of
      schedule for all children aged 9 to 14 months. During an outbreak of measles,
      children aged 6 months or older, who have not previously been vaccinated against
      measles, mumps and rubella, should receive a first dose as soon as possible, and
      those who have had a first dose should receive a second dose as soon as possible,
      provided that a minimum of one month has elapsed between the two doses.

PMID- 29208118
TI  - Case-control study for risk factors for Q Fever in southwest England and Northern
      Ireland.
AB  - Q fever (Coxiella burnetti) is thought to account for 1% (700 cases) of community
      acquired pneumonia in the United Kingdom each year, and can result in serious
      complications such as endocarditis. Although outbreaks have frequently been
      reported worldwide, the causes are often not clearly identified and there have
      been few studies of risk factors in sporadic cases. We conducted a matched case
      control study. Cases of acute Q fever in people aged over 15 years in southwest
      England and Northern Ireland were identified from January 2002 to December 2004.
      Controls were matched for age, sex and the general practice at which they were
      registered. Questionnaires asking about contact with animals, and leisure and
      work activities, were posted to cases and controls. Questionnaires were completed
      by 39/50 (78%) of the cases and 90/180 (50%) of the controls. In the single
      variable analysis, occupational exposure to animals or animal products was the
      only risk factor associated with cases at the 5% level (P=0.05, odds ratio (OR)
      3.4). Long term illness appeared to be significantly protective (P=0.03, OR 0.3).
      In multivariable analysis the strength of association between occupational
      exposure and illness remained high (OR 3.6, 95% confidence interval (CI) 0.9 to
      14.8) and smoking emerged as a possible risk factor. This is the first case
      control study to identify occupational exposure to animals or animal products as
      the most likely route of infection in sporadic cases as opposed to outbreaks.

PMID- 29208120
TI  - Surveillance of listeria infections in Europe.
AB  - In addition to the economic consequences and threats associated with outbreaks,
      listeriosis remains of great public health concern, as it has one of the highest
      case fatality rates of all the foodborne infections (20%-30%), and has common
      source epidemic potential. Changes in the way food is produced, distributed and
      stored have created the potential for diffuse and widespread outbreaks involving
      many countries. In 2002, a survey was carried out to assess the need for and the
      feasibility of a European network on listeria infections in humans. Data on
      surveillance systems and laboratory methods were collected through two postal
      surveys sent to the national Centres for communicable disease surveillance and to
      the listeria reference laboratories. Surveillance systems for listeria infections
      were in operation in 16 out of the 17 countries surveyed, and 16 countries had a
      national reference laboratory (NRL). All countries based their case definition of
      listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed
      at least one typing method on human strains. At least 13 countries already
      carried out or expressed willingness to carry out characterisation of isolates by
      pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from
      human cases following a standard protocol. The participants concluded that there
      was a clear added value to having a European surveillance network for listeria
      infections, particularly for outbreak detection and investigation, and that a
      surveillance network based on the existing national surveillance systems was
      feasible.

PMID- 29208119
TI  - Comparative analysis of the Burkholderia cenocepacia K56-2 essential genome
      reveals cell envelope functions that are uniquely required for survival in
      species of the genus Burkholderia.
AB  - Burkholderia cenocepacia K56-2 belongs to the Burkholderia cepacia complex, a
      group of Gram-negative opportunistic pathogens that have large and dynamic
      genomes. In this work, we identified the essential genome of B. cenocepacia K56-2
      using high-density transposon mutagenesis and insertion site sequencing (Tn-seq
      circle). We constructed a library of one million transposon mutants and
      identified the transposon insertions at an average of one insertion per 27 bp.
      The probability of gene essentiality was determined by comparing of the insertion
      density per gene with the variance of neutral datasets generated by Monte Carlo
      simulations. Five hundred and eight genes were not significantly disrupted,
      suggesting that these genes are essential for survival in rich, undefined medium.
      Comparison of the B. cenocepacia K56-2 essential genome with that of the closely
      related B. cenocepacia J2315 revealed partial overlapping, suggesting that some
      essential genes are strain-specific. Furthermore, 158 essential genes were
      conserved in B. cenocepacia and two species belonging to the Burkholderia
      pseudomallei complex, B. pseudomallei K96243 and Burkholderia thailandensis E264.
      Porins, including OpcC, a lysophospholipid transporter, LplT, and a protein
      involved in the modification of lipid A with aminoarabinose were found to be
      essential in Burkholderia genomes but not in other bacterial essential genomes
      identified so far. Our results highlight the existence of cell envelope processes
      that are uniquely essential in species of the genus Burkholderia for which the
      essential genomes have been identified by Tn-seq.

PMID- 29208122
TI  - Cryptosporidium outbreak linked to interactive water feature, UK: importance of
      guidelines.
AB  - A need for national guidelines relating to interactive water features was
      highlighted following three outbreaks of cryptosporidiosis in the United Kingdom,
      all of which were related to public water features. In August 2003 the Health
      Protection Agency South West of England was notified of an outbreak of
      cryptosporidiosis associated with an interactive water feature designed for water
      play within an adventure park. The water feature was implicated following samples
      with a high coliform count and the presence of faecal coliforms. A case was
      defined as any child (younger than 16 years of age) who had visited the park
      during August and who subsequently had gastrointestinal symptoms and a faecal
      sample positive for cryptosporidium. Seventy one children were identified in the
      cohort. This outbreak of cryptosporidiosis was characterised by a very high
      attack rate (89%), relatively severe in duration (median 8 days) and had a
      relatively high hospital admission (16% of cases). The epidemic curve was
      consistent with a point source of infection, which corresponded to the date 80%
      of the cohort visited the park. This outbreak has similarities to two other
      cryptosporidiosis outbreaks reported in England in 2003 that involved public
      water features. These outbreaks raise issues about the operation and maintenance
      of water-based recreational attractions that very often involve children. The
      paper reflects on the basic control measures that can be taken and highlights the
      need for guidelines, especially since such attractions are becoming increasingly
      common. The Pool Water Treatment Advisory Group in United Kingdom has now
      produced guidelines.

PMID- 29208124
TI  - HIV incidence increasing in MSM in Germany: factors influencing infection
      dynamics.
AB  - After an initial peak in the mid-1980s, HIV incidence in men who have sex with
      men (MSM) declined in most western industrialised countries and then levelled off
      during the 1990s. Since the late 1990s, increasing numbers of newly diagnosed HIV
      infections in MSM have been observed in the majority of countries with large and
      visible MSM communities. Based on a review of national and international
      behavioural surveillance studies of MSM and national HIV surveillance data, we
      propose a model for the HIV epidemic in MSM in Germany. The model includes
      aspects such as individuals' increasing numbers of sexual partners and increasing
      frequency of unprotected anal intercourse, conditional condom use based on real
      or perceived HIV status of sexual partners (HIV 'serosorting') and sexual role
      assignments (insertive versus receptive based on HIV status (HIV
      'seropositioning'), selection of partners and formation of sexual networks
      through seeking sexual partners on the internet, the introduction of HAART and
      changing HAART treatment strategies. All these aspects have been shown or are
      suspected to increase or decrease HIV transmission risk in MSM. We conclude that
      increasing HIV incidence in MSM in recent years has been fuelled by a spread of
      HIV in high-risk sexual networks with an increasing proportion of infections
      transmitted during highly infective early HIV infection, acquired mostly from
      casual sexual partners.

PMID- 29208121
TI  - Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not
      distinguish bacteraemia from endocarditis.
AB  - Most Staphylococcus aureus isolates can cause invasive disease given the right
      circumstances, but it is unknown if some isolates are more likely to cause severe
      infections than others. S. aureus bloodstream isolates from 120 patients with
      definite infective endocarditis and 121 with S. aureus bacteraemia without
      infective endocarditis underwent whole-genome sequencing. Genome-wide association
      analysis was performed using a variety of bioinformatics approaches including SNP
      analysis, accessory genome analysis and k-mer based analysis. Core and accessory
      genome analyses found no association with either of the two clinical groups. In
      this study, the genome sequences of S. aureus bloodstream isolates did not
      discriminate between bacteraemia and infective endocarditis. Based on our study
      and the current literature, it is not convincing that a specific S. aureus
      genotype is clearly associated to infective endocarditis in patients with S.
      aureus bacteraemia.

PMID- 29208123
TI  - Outbreak of human listeriosis associated with tomme cheese in northwest
      Switzerland, 2005.
AB  - During an eight week period in spring 2005, 10 cases of listeriosis were reported
      in a small area of northwest Switzerland (150 000 inhabitants). Eight cases were
      in older immunocompromised patients who became ill with bacteraemia (three
      deaths), and two cases were in pregnant women who had septic abortion.

PMID- 29208125
TI  - Rabies in Europe in 2005.
AB  - Rabies is still present in Europe in 2005. Its incidence in humans remains
      limited (fewer than 5 human cases per year) through the application of strict
      prophylactic measures (anti-rabies treatment) and by means of veterinary rabies
      control measures in the domesticated and wild animal populations. The main
      indigenous animal reservoirs are: the dog in eastern European countries and on
      the borders with the Middle East; the fox in central and eastern Europe; the
      racoon dog in northeastern Europe; and the insectivorous bat throughout the
      entire territory. Finally, each year, cases of animals with rabies imported from
      enzootic areas are reported, showing the permeability of borders and traveller's
      lack of consideration of the rabies risk. These importations constantly threaten
      the rabies-free status of terrestrial animals in western European countries and
      complicate the therapeutic decisions taken by physicians in the absence of
      information regarding the biting animal.

PMID- 29208126
TI  - Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003.
AB  - An outbreak of highly pathogenic avian influenza A virus subtype H7N7 began in
      poultry farms in the Netherlands in 2003. Virus infection was detected by RT-PCR
      in 86 poultry workers and three household contacts of PCR-positive poultry
      workers, mainly associated with conjunctivitis. To determine the magnitude of and
      risk factors for human-to-human transmission of influenza A/H7N7 in the
      Netherlands, a retrospective cohort study among household members of infected
      poultry workers was undertaken. In total, 33 (58.9%) of 56 (among 62)
      participants who provided blood samples had positive H7 serology, using single
      convalescent serum samples obtained at least 3 weeks after onset of symptoms of
      the index case. Eight household members (12.9%) reported symptoms (conjunctivitis
      and/or ILI), of which four of five (80.0%) tested seropositive. On univariate
      analysis, significant risk factors for seropositivity included having at least
      two toilets, a pet bird, and using cloth handkerchiefs. It was not possible to
      obtain a stable model for binomial regression for the outcome of A/H7N7
      infection. Further seroprevalence studies among contacts of asymptomatic H7 cases
      should be conducted.

PMID- 29208127
TI  - The Early Warning and Response System for communicable diseases in the EU: an
      overview from 1999 to 2005.
AB  - Under Decision 2119/98/EC of the European Parliament and of the Council, a
      network for epidemiological surveillance and control of communicable diseases in
      the Community was set up in 1998. One pillar of Decision 2119/98/EC is the early
      warning and response system (EWRS). The main objective of the network is to
      establish permanent communication between European Union (EU) Member States'
      public health authorities, which are responsible for determining the measures
      required to control communicable disease-related events. Since 1998, a web based
      informatics tool has been developed in order to allow information to be shared
      between the relevant public health authorities. Between 1998 and December 2005, a
      total of 583 messages were circulated through the EWRS, notifying 396 events. The
      information shared through the system helped to coordinate public health measures
      in the EU. However, only few events prompted specific measures at Community level
      and most of them were controlled with public health measures applied at national
      level. Major events (such as the Severe Acute Respiratory Syndrome) and the
      results of simulation exercises prompted the Commission to upgrade the
      informatics system on the basis of user needs. Since 1 May 2004 the 10 newest
      Member States have provided information under the current legislation and since
      April 2005 the European Centre for Disease Prevention and Control (ECDC) is part
      of the system. Future developments will include a link between the existing EWRS
      and the communication platform currently developed by the ECDC.

PMID- 29208128
TI  - Surveillance of listeriosis in Finland during 1995-2004.
AB  - We analysed the surveillance data from listeriosis cases notified to the Finnish
      National Infectious Diseases Register between 1995 and 2004 and describe our
      recent experience in investigating clusters of listeriosis cases. The number of
      annual cases varied between 18 and 53 but no trends in incidence were identified
      (average annual incidence was 7 cases per million inhabitants).

PMID- 29208129
TI  - Pneumococcal disease surveillance in Europe.
AB  - Pneumococcal disease (Pnc) is responsible for invasive pneumococcal disease (IPD)
      - mainly meningitis and septicaemia - and is an infection of public health
      importance in Europe. Following the licensure of an effective conjugate vaccine
      (PCV) in Europe, several European countries, including France, Germany, the
      Netherlands, Norway, Spain and the United Kingdom, are introducing universal Pnc
      childhood immunisation programmes. As part of a European Union (EU) funded
      project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed in
      late 2003 to each of the current 25 European Union member states as well as
      Norway and Switzerland to get a clearer picture of national surveillance for
      invasive pneumococcal disease (IPD) in Europe. All respondents were contacted in
      2006 and asked to provide an update to the questionnaire. Twenty two of the 27
      countries targeted completed and returned the questionnaire. Four of the 22
      responding countries have no reporting requirement for IPD. Eighteen countries
      reported a total of 27 national surveillance systems. Case definitions employed
      in these systems differed. Fourteen of the 18 countries reported collection of
      IPD strains to a single reference lab for serotyping and in 12 countries to a
      single laboratory for susceptibility testing. Thirteen countries undertook
      laboratory quality assurance. Information on age and sex were widely collected,
      but only 11/27 systems collected information on pneumococcal polysaccharide
      vaccine status, while 5/27 systems collected information on pneumococcal
      conjugate vaccine status. The incidence of IPD reported in each of the 18
      countries ranged from 0.4 to 20/100 000 in the general population, with a total
      of 23 470 IPD cases reported over a 12 month period. Surveillance for IPD in
      Europe is very heterogeneous. Several countries lack surveillance systems. Large
      differences in reported disease incidence may reflect both true differences, and
      also variations in patient and healthcare factors, including surveillance. If IPD
      surveillance in Europe can be strengthened, countries will be able to make
      informed decisions regarding the introduction of new pneumococcal vaccines and
      also to monitor and compare the impact and effectiveness of new programmes.

PMID- 29208131
TI  - Using sentinel surveillance to monitor effectiveness of influenza vaccine is
      feasible: A pilot study in Denmark.
AB  - The influenza vaccine for the season 2003/04 did not contain the circulating
      A(H3N2)/Fujian virus strain. Vaccine effectiveness (VE) estimates were needed but
      unavailable. We explored whether or not laboratory based influenza surveillance
      can be used to estimate VE. We carried out a case-control study nested within
      Danish sentinel surveillance. A case was defined as a person aged 25 or above
      with A(H3N2)/Fujian/411/02 influenza. Four controls per case, matched on age
      groups and time, were selected from clients of sentinel practitioners (SP) who
      reported cases. SPs collected the following data in structured one-page
      questionnaires: vaccination status, chronic illness and previous pneumococcal
      vaccination. We sent postal survey questionnaires to participating SPs to assess
      acceptability and simplicity of data collection. Twenty four cases were
      identified. Data from 19 case-control sets were analysed. One control was
      excluded because information on vaccination status was missing. Two of the 19
      cases and 11 of 75 controls had been vaccinated against influenza. The VE
      adjusted for chronic illness was 33% (95% CI 0%-88%) and 37% (95% CI 0%-89%) when
      excluding 5 controls with influenza-like illness. Twenty two SPs returned survey
      questionnaires. Fifteen of 17 SPs reported that it was easy to find controls. SPs
      collected data through interviews and clinical notes, spending 1 to 5 minutes per
      case and 5 to 15 minutes for all four controls. Nineteen of 22 SPs considered the
      amount of time they spent on the study to be acceptable, 17 said that they would
      like to participate again, and none ruled out further participation. Le controle
      de l'EV au sein des systemes de surveillance sentinelle est faisable. Les nombres
      restreints de notre etude limitent l'interpretation de l'EV. Une etude etendue a
      l'echelle europeenne, comprenant plusieurs pays, pourrait surmonter cette
      limitation et offrir des evaluations de l'efficacite vaccinale plus tot dans la
      saison, pour differents groupes d'age et pour des souches virales emergentes,
      incluant les sous-types nouveaux et pandemiques. Monitoring VE within sentinel
      surveillance systems is feasible. The small numbers in our study limit
      interpretation of VE. Expansion to a European multicountry study could overcome
      this limitation and provide VE estimates earlier in the season, for different age
      groups and emerging virus strains, including new and pandemic subtypes.

PMID- 29208130
TI  - Novel large-scale chromosomal transfer in Bacteroides fragilis contributes to its
      pan-genome and rapid environmental adaptation.
AB  - Bacteroides fragilis, an important component of the human gastrointestinal
      microbiota, can cause lethal extra-intestinal infection upon escape from the
      gastrointestinal tract. We demonstrated transfer and recombination of large
      chromosomal segments from B. fragilis HMW615, a multidrug resistant clinical
      isolate, to B. fragilis 638R. In one example, the transfer of a segment of ~435
      Kb/356 genes replaced ~413 Kb/326 genes of the B. fragilis 638R chromosome. In
      addition to transfer of antibiotic resistance genes, these transfers (1) replaced
      complete divergent polysaccharide biosynthesis loci; (2) replaced DNA inversion
      controlled intergenic shufflons (that control expression of genes encoding starch
      utilization system outer membrane proteins) with more complex, divergent
      shufflons; and (3) introduced additional intergenic shufflons encoding divergent
      Type 1 restriction/modification systems. Conjugative transposon-like genes within
      a transferred segment and within a putative integrative conjugative element
      (ICE5) ~45 kb downstream from the transferred segment both encode proteins that
      may be involved in the observed transfer. These data indicate that chromosomal
      transfer is a driver of antigenic diversity and nutrient adaptation in
      Bacteroides that (1) contributes to the dissemination of the extensive B.
      fragilis pan-genome, (2) allows rapid adaptation to a changing environment and
      (3) can confer pathogenic characteristics to host symbionts.

PMID- 29208132
TI  - Wound botulism in injectors of drugs: upsurge in cases in England during 2004.
AB  - Wound infections due to Clostridium botulinum were not recognised in the UK and
      Republic of Ireland before 2000. C. botulinum produces a potent neurotoxin which
      can cause paralysis and death. In 2000 and 2001, ten cases were clinically
      recognised, with a further 23 in 2002, 15 in 2003 and 40 cases in 2004. All cases
      occurred in heroin injectors. Seventy cases occurred in England; the remainder
      occurred in Scotland (12 cases), Wales (2 cases) and the Republic of Ireland (4
      cases). Overall, 40 (45%) of the 88 cases were laboratory confirmed by the
      detection of botulinum neurotoxin in serum, or by the isolation of C. botulinum
      from wounds. Of the 40 cases in 2004, 36 occurred in England, and of the 12 that
      were laboratory confirmed, 10 were due to type A. There was some geographical
      clustering of the cases during 2004, with most cases occurring in London and in
      the Yorkshire and Humberside region of northeast England.

PMID- 29208133
TI  - Outbreak of Salmonella enterica serotype Manhattan infection associated with meat
      products, France, 2005.
AB  - Between August 2005 and March 2006 in France, 69 cases of Salmonella enterica
      serotype Manhattan (Salmonella Manhattan) were reported, 51 (74%) of them from
      southeastern France. At the time of the alert (November 2005), 13 cases and 33
      controls were interviewed. Cases were more likely than controls to have eaten
      pork sausages (OR=5.9, confidence interval CI [1.3; 26.9]) and beef (OR=9.3, CI
      [1.3; 68.6]). At the same time, 19 strains of Salmonella Manhattan isolated from
      meat products in southeastern France, reported to the French food safety agency
      (Afssa, Agence francaise de securite sanitaire des aliments) in September and
      November 2005, had an indistinguishable PFGE profile to the 7 human isolates of
      Salmonella Manhattan from the outbreak in southeastern France. Trace-back
      investigations revealed that pork samples came from one wholesaler whose pork
      products had tested positive for S. Manhattan during routine food testing in
      August 2005. This wholesaler supplied retail outlets in southeastern France.
      Additionally, a slaughterhouse supplying the wholesaler was inspected and
      widespread contamination with Salmonella spp. and S. Manhattan was found.
      Cooperation between the national agencies in charge of human health (Institut de
      veille sanitaire, InVS) and food safety (Afssa) allowed us to determine the most
      probable source of contamination and to take appropriate control measures.

PMID- 29208134
TI  - Epidemiologic surveillance system implemented in the Hautes-Alpes District,
      France, during the Winter Olympic Games, Torino 2006.
AB  - Some of the competitions of the Olympic Winter Games in Torino, 10 to 26 February
      2006, were organised in France near the city of Briancon, in the department of
      Hautes-Alpes. An epidemiologic surveillance system was set up by the local health
      authorities. The goals were to detect in a timely fashion any phenomenon which
      could justify prevention or sanitary control action, and to guide interventions
      in the case of outbreak or environmental pollution. Surveillance was implemented
      from 30 January to15 March 2006 in the Briancon area. Mortality was tracked using
      by analysing the number and cause of deaths. A sentinel network of general
      practitioners was set up and reported the frequency of acute gastroenteritis,
      influenza-like illness and measles. Medical laboratories provided data about the
      analyses they undertook. Hospital emergency department and emergency ambulance
      service activities were followed up. Statutory notification diseases and toxic
      effects of carbon monoxide surveillances were reinforced. Analysed data were
      transmitted daily to the health authorities. A French/English report was sent
      weekly to all participants. The participation rate was close to 100%, and data
      transmission deadlines were respected. No adverse health event was identified.
      The strong acceptability of this surveillance system comes from its good
      understanding by the participants. This surveillance, structured around routine
      and ad-hoc systems, allowed the establishment of the foundations of a network to
      be used in case of outbreak or environmental pollution.

PMID- 29208135
TI  - A pseudo-outbreak of human A/H5N1 infections in Greece and its public health
      implications.
AB  - The recent wide geographic spread of the highly pathogenic avian influenza A/H5N1
      virus has important public health implications. Several wild migratory birds were
      confirmed to be infected with avian influenza A/H5N1 in Greece in February and
      March 2006. The aim of this paper is to report data from potential H5N1 human
      cases that presented to local hospitals during this period with a respiratory
      infection and expressing concern about exposure to avian influenza. A case
      control investigation was conducted that included case identification with the
      use of a structured definition, review of epidemiological and clinical
      characteristics and molecular testing for avian influenza A/H5N1. The setting was
      the entire country of Greece during February and March 2006. The main outcomes
      were rates of possible cases (meeting both a clinical and an epidemiological
      criterion) and clinical or epidemiological characteristics differentiating them
      from potential cases that met either one of the criteria of a possible case, but
      not both. Twenty six potential patients (81% of whom met a clinical criterion,
      and 39% of whom met an epidemiological criterion) presented and most (85%) were
      admitted in local hospitals during the period of interest. The majority of cases
      (85%) were observed in northern Greece where most of the confirmed A/H5N1 avian
      cases were documented. Five of the 26 evaluated patients met the definition of a
      possible case. These clustered within the early period of confirmed A/H5N1 cases
      in wild migratory birds (P=0.05). Molecular testing was negative for all possible
      cases. Application of a revised case definition constructed according to newer
      European Union guidance resulted in the exclusion of two possible cases. Several
      potential A/H5N1 human cases were recently identified in Greece. Both the timing
      of identification and the geographical location of potential cases suggest an
      increased awareness on the part of the general public, as well as poor
      interpretation of the case definition by the clinicians.

PMID- 29208136
TI  - From evaluation to continuous quality assurance of surveillance systems.
AB  - Surveillance systems have been described as the nerve cells of public health with
      afferent arms receiving information, cell bodies analysing the information and
      efferent arms initiating appropriate action or further distribution of
      information [1]. Increasing numbers of scientific publications on the methodology
      and evaluation of surveillance systems seem to underline the importance of
      surveillance systems in public health. The most often cited references in these
      publications appear to be the definition of public health surveillance by Thacker
      and Berkelman [2] and variations thereof, and the recommendations for evaluating
      surveillance systems from 1988 [3] and its update from 2002 written by working
      groups at the Centers for Disease Control and Prevention (CDC) in the United
      States[4].

PMID- 29208137
TI  - Rectal lymphogranuloma venereum surveillance in France 2004-2005.
AB  - Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused
      by Chlamydia trachomatis strains belonging to the L1, L2 or L3 genotype. An alert
      about an outbreak of LGV among MSM in the Netherlands was published in January
      2004. The first cases of rectal LGV in France were retrospectively diagnosed in
      March 2004 and sentinel surveillance for LGV was implemented in April 2004. Most
      of the participating centres were located in the cities of Paris and Bordeaux.
      Only confirmed rectal LGV cases were included in the surveillance. Rectal
      specimens from men that were found to be positive for C trachomatis by PCR were
      sent to the National Reference Centre for Chlamydia infection for genotyping.
      Simple epidemiological data provided by clinicians and genotyping results were
      sent to the Institut de Veille Sanitaire (InVS) where data were anonymously
      recorded. A total of 328 C. trachomatis rectal strains isolated in men were
      genotyped by the end of December 2005. Of these, 244 (74%) were LGV strains
      belonging to the L2 genotype. No L1 or L3 C. trachomatis genotype was found.
      Diagnosis was made retrospectively for 46 cases. The median age of patients with
      LGV was 39 years. HIV status was known for 96 patients: 82/96 (85%) were HIV
      infected. Most LGV cases were diagnosed in the Paris area (92%). Among the
      remaining 26% C. trachomatis strains, genotypes Da and G were the most frequent.
      As with syphilis in recent years, the emergence of LGV in Europe is mainly
      affecting HIV-infected MSM. The screening and treatment of STIs should be
      included in the clinical follow-up of all HIV-infected MSM.

PMID- 29208139
TI  - You're the Flight Surgeon.
AB  - Timboe AM. You're the flight surgeon: seborrheic dermatitis. Aerosp Med Hum
      Perform. 2017; 88(1):68-70.

PMID- 29208140
TI  - Suspected cases of intracontinental Burkholderia pseudomallei sequence type
      homoplasy resolved using whole-genome sequencing.
AB  - Burkholderia pseudomallei is a Gram-negative environmental bacterium that causes
      melioidosis, a disease of high mortality in humans and animals. Multilocus
      sequence typing (MLST) is a popular and portable genotyping method that has been
      used extensively to characterise the genetic diversity of B. pseudomallei
      populations. MLST has been central to our understanding of the underlying
      phylogeographical signal present in the B. pseudomallei genome, revealing
      distinct populations on both the intra- and the inter-continental level. However,
      due to its high recombination rate, it is possible for B. pseudomallei isolates
      to share the same multilocus sequence type (ST) despite being genetically and
      geographically distinct, with two cases of 'ST homoplasy' recently reported
      between Cambodian and Australian B. pseudomallei isolates. This phenomenon can
      dramatically confound conclusions about melioidosis transmission patterns and
      source attribution, a critical issue for bacteria such as B. pseudomallei that
      are of concern due to their potential for use as bioweapons. In this study, we
      used whole-genome sequencing to identify the first reported instances of
      intracontinental ST homoplasy, which involved ST-722 and ST-804 B. pseudomallei
      isolates separated by large geographical distances. In contrast, a third
      suspected homoplasy case was shown to be a true long-range (460 km) dispersal
      event between a remote Australian island and the Australian mainland. Our results
      show that, whilst a highly useful and portable method, MLST can occasionally lead
      to erroneous conclusions about isolate origin and disease attribution. In cases
      where a shared ST is identified between geographically distant locales, whole
      genome sequencing should be used to resolve strain origin.

PMID- 29208142
TI  - Investigation of a tuberculosis cluster at a job centre in Manchester, United
      Kingdom.
AB  - During the summer of 2005, four cases of active tuberculosis from the same
      occupational setting were investigated in Manchester, UK. The index case had been
      diagnosed in December of the previous year. At that stage the closest
      occupational contacts had been screened, all of whom were assessed as being free
      from active disease, and none had met nationally recommended criteria for
      chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work
      contacts developed progressive primary extrapulmonary (pleural) TB. Following a
      detailed risk assessment, the screening programme was widened to include 137
      staff who worked at the job centre (employment agency) where the first four cases
      had been found. This screening programme was based on tuberculin Mantoux testing,
      CXR and gamma-interferon testing. Of these 137 contacts screened, one additional
      person was found to have active disease and six others were offered
      chemoprophylaxis for LTBI. The isolates from the index case and the first two
      secondary cases were indistinguishable on VNTR-MIRU (variable number tandem
      repeat - mycobacterial interspersed repetitive unit) typing at 15 loci. No
      samples were available for testing from the fourth case of active disease.
      Management of this incident has benefited from the evolving fields of both
      genotyping and diagnostic testing for LTBI. However, further research into the
      epidemiological inferences made through genotyping, as well as the significance
      of a positive gamma-interferon test in assessing the risk of development of
      active disease, is still required.

PMID- 29208141
TI  - Enhanced Surveillance of Infectious Diseases : the 2006 FIFA World Cup
      experience, Germany.
AB  - The 2006 FIFA World Cup was held in 12 German cities between 9 June and 9 July
      2006. We identified a need to accelerate and sensitise the pre-existing
      surveillance system for infectious diseases in order to timely detect adverse
      health events during the World Cup. Enhanced surveillance, based on Germany's pre
      existing system of mandatory notifications was conducted between 7 June and
      11July 2006 in the 12 World Cup cities by: accelerating frequency of electronic
      data transmission of case-definition based notifiable diseases from weekly to
      daily transmission, additional reporting of non-case definition-based infectious
      disease events, lay and expert press screening and intensifying communication
      between all stakeholders of the surveillance system. Median delay of notification
      data transmission from the community to the federal level was reduced from three
      days to one day. The enhanced reporting system detected a norovirus outbreak in
      the International Broadcast Centre in Munich with 61 epidemiologically linked
      cases within the first week after onset, as well as four single cases related to
      the World Cup, two of them with relevance for the International Health
      Regulations. After the World Cup, all surveillance stakeholders agreed that
      communication between local, state and federal levels had improved considerably.
      Unlike the majority of health planners of previous mass gatherings in the last
      decade we did not introduce syndromic surveillance. Nevertheless, enhancement of
      infectious disease surveillance successfully detected adverse health events in a
      timely manner during the FIFA World Cup. Additionally, it provided a valuable
      communication and networking exercise for potentially critical health-related
      events. We recommend continuing daily notification data transmission for routine
      infectious disease surveillance in Germany.

PMID- 29208143
TI  - SmiNet-2: Description of an internet-based surveillance system for communicable
      diseases in Sweden.
AB  - Electronic systems for communicable diseases surveillance enhance quality by
      simplifying reporting, improving completeness, and increasing timeliness. In this
      article we outline the ideas and technologies behind SmiNet-2, a new
      comprehensive regional/national system for communicable disease surveillance in
      Sweden. The system allows for reporting from physicians (web form) and
      laboratories (direct from lab data system) over the internet. Using a unique
      personal identification number, SmiNet-2 automatically merges clinical and
      laboratory notifications to case records. Privileged users, at national and
      county level, work against a common central server containing all notifications
      and case records. In addition, SmiNet-2 has separate county servers with tools
      for outbreak investigations, contact tracing and case management. SmiNet-2 was
      first used in September 2004. Individual counties receive up to 90% of all
      notifications electronically. In its first year, SmiNet-2 received 54 980
      clinical notifications and 32 765 laboratory notifications, which generated 58
      891 case records. Since most clinicians in Sweden have easy access to the
      internet, a general web-based reporting has been feasible, and it is anticipated
      that within a few years all reporting to SmiNet-2 will be over the internet. In
      this context, some of the major advantages of SmiNet-2 when compared with other
      systems are timeliness in the dataflow (up to national level), the full
      integration of clinical and laboratory notifications, and the capability to
      handle more than 50 diseases with tailor-made notification forms within one
      single system.

PMID- 29208144
TI  - Significant increase of listeriosis in Germany - Epidemiological patterns 2001
      2005.
AB  - Listeriosis has been a mandatorily notifiable disease in Germany since January
      2001. Clinical cases with isolation of Listeria monocytogenes from sterile
      specimens or neonates are reported to the Robert Koch-Institut. Listeriosis
      incidence significantly increased from 0.26 per 100 000 inhabitants (217 cases)
      in 2001 to 0.62 per 100 000 (519 cases) in 2005.

PMID- 29208145
TI  - SurvNet@RKI - a multistate electronic reporting system for communicable diseases.
AB  - In 2001 Germany implemented a new electronic reporting system for surveillance of
      notifiable infectious diseases (SurvNet@RKI). The system is currently being used
      in all 431 local health departments (LHD), the 16 state health departments (SHD)
      and the Robert Koch-Institut (RKI), the national agency for infectious disease
      epidemiology. The SurvNet@RKI software is written in MS Access 97 and Visual
      Basic and it supports MS Access as well as MS SQL Server database management
      systems as a back-end. The database is designed as a distributed, dynamic
      database for 73 reporting categories with more than 600 fields and about 7000
      predefined entry values. An integrated version management system documents
      deletion, undeletion, completion and correction of cases at any time and entry
      level and allows reproduction of previously conducted queries. Integrated
      algorithms and help functions support data quality and the application of case
      definitions. RKI makes the system available to all LHDs and SHDs free of charge.
      RKI receives an average of 300 000 case reports and 6240 outbreak reports per
      year through this system. A public web-based query interface, SurvStat@RKI,
      assures extensive and timely publication of the data. During the 5 years that
      SurvNet@RKI has been running in all LHDs and SHDs in Germany it has coped well
      with a complex federal structure which makes this system particularly attractive
      to multinational surveillance networks. The system is currently being migrated to
      Microsoft C#/.NET and transport formats in XML. Based on our experiences, we
      provide recommendations for the design and implementation of national or
      international electronic surveillance systems.

PMID- 29208146
TI  - Epidemiology of invasive meningococcal disease in France in 2003.
AB  - National surveillance of invasive meningococcal disease (IMD) is based on
      mandatory reporting. The case definition for surveillance notification was
      changed in mid-2002 to include cases without microbiological confirmation. The
      IMD alert detection system was enhanced in 2003 with daily reporting and weekly
      analysis by district, serogroup, and age. Evaluation of the exhaustivity of the
      surveillance with capture-recapture analysis allowed correcting for
      underreporting. In 2003, 803 cases were reported. After correction for under
      reporting, the estimated incidence was 1.78 / 100 000. After excluding 'new'
      cases reported with new definition criteria, the 2002-2003 increase was 4%.
      Incidence decreased with age, with the highest values in infants less than 1 year
      (20/100 000), children aged between 1 and 2 years (11/100 000) and in teenagers
      of 17 years old(7/100 000). The overall case fatality rate was 12%. Fifty nine
      per cent of cases were due to serogroup B, 32% to C, 5% to W135, and 4% to Y and
      non-groupable meningococci. Patients with purpura fulminans treated with
      intravenous antibiotics before admission to hospital were shown to have lower
      fatality rates than those not treated. In 2001-2003, 5 situations required
      particular attention: two clusters of serogroup B IMD had set off mass
      prophylaxis, one outbreak due to a specific B IMD clonal complex with high case
      fatality rate, and two districts crossed the alert threshold for serogroup C IMD,
      2/100 000, and mass vaccination was recommended.

PMID- 29208147
TI  - Shiga toxin-producing Escherichia coli (STEC) O157 outbreak, The Netherlands,
      September - October 2005.
AB  - In September 2005, the first national food-related outbreak of Shiga toxin (Stx)
      producing Escherichia coli (STEC) O157 was investigated in the Netherlands. A
      total of 21 laboratory-confirmed cases (including one secondary case), and
      another 11 probable cases (two primary and nine secondary cases) were reported in
      patients who became ill between 11 September and 10 October 2005. Preliminary
      investigation suggested consumption of a raw beef product, steak tartare (in the
      Netherlands also known as 'filet americain'), and contact with other symptomatic
      persons as possible risk factors. A subsequent case-control study supported the
      hypothesis that steak tartare was the source of the outbreak (matched odds ratio
      (OR) 272, 95% confidence interval (CI) 3 - 23211). Consumption of ready-to-eat
      vegetables was also associated with STEC O157 infection (matched OR 24, 95% CI
      1.1 - 528), but was considered a less likely source, as only 40% of the cases
      were exposed. Samples of steak tartare collected from one chain of supermarkets
      where it is likely that most patients (67%) bought steak tartare, all tested
      negative for STEC O157. However, sampling was done three days after the date of
      symptom onset of the last reported case. Since 88% of the cases became ill within
      a two week period, point source contamination may explain these negative results.
      It is concluded that steak tartare was the most likely cause of the first
      national food-related outbreak of STEC O157 in the Netherlands.

PMID- 29208148
TI  - Ascertainment of meningococcal disease in Europe.
AB  - Meningococcal disease surveillance in most countries is based upon a combination
      of statutory notification systems and laboratory reporting, both of which are
      recognised to underestimate the true burden of disease. The incidence of
      meningococcal disease varies throughout Europe, and although there are many
      reasons for this, it is important to quantify the degree of under-ascertainment
      in order to validate international comparisons. Here, we review the literature on
      the ascertainment of meningococcal disease in Europe and the available methods
      for estimating the degree of under-reporting. We found that the sensitivity of
      surveillance varies between countries and over time, with estimates ranging from
      40% to 96%. We identified five methods suitable for conducting ascertainment
      studies, from simple comparative studies to more complicated capture-recapture
      and regression analyses. Studies of ascertainment may be used to identify
      weaknesses and biases in surveillance data, and facilitate the improvement of
      these systems. These findings are relevant to the surveillance of other
      infectious diseases, particularly those with lower mortality and a lower public
      profile than meningococcal disease, for which ascertainment may be worse.

PMID- 29208150
TI  - Exercise Countermeasures: The First Decade on ISS.

PMID- 29208151
TI  - Tattooing, permanent makeup and piercing in Amsterdam; guidelines, legislation
      and monitoring.
AB  - Tattooing, body piercing and permanent makeup are increasing in popularity. Here,
      we describe the procedures involved in these practices, their risks, the content
      of guidelines developed by the Municipal Health Service in Amsterdam (the
      Netherlands) to reduce infection risks, the legislation in the city of Amsterdam,
      and results of monitoring in tattoo and piercing studios.

PMID- 29208152
TI  - Diagnosis of non-viral sexually transmitted infections in Lithuania and
      international recommendations.
AB  - The aim of this study is to evaluate the range, quality and availability of
      diagnostic services for non-viral sexually transmitted infections (STIs), i.e. C.
      trachomatis, N. gonorrhoeae, T. vaginalis and T. pallidum, in Lithuania from
      September 2002 to December 2003. Surveillance data describing the organisation
      and performance characteristics of non-viral STI diagnostic services in Lithuania
      were collected using a questionnaire and subsequent site-visits. International
      evidence-based recommendations for non-viral STI diagnosis were used to evaluate
      the quality of the STI diagnostics. There were 171 facilities providing non-viral
      STI diagnostic services for the 3.5 million inhabitants of Lithuania. However,
      only 6% (n=9) of the respondents (n=153) could provide a confirmatory diagnosis,
      in accordance with international recommendations, for the full minimum range of
      relevant non-viral STIs in Lithuania, i.e. C. trachomatis, N. gonorrhoeae, T.
      pallidum, and T. vaginalis. In addition, accessibility to STI diagnostic services
      differed significantly among the different counties in Lithuania. Several of the
      respondents analysed low numbers of samples each year, and overall the sampling
      size was extremely low, especially for C. trachomatis diagnostics. In Lithuania,
      optimisation of non-viral STI diagnostics as well as of epidemiological
      surveillance and management of STIs is crucial. It may be worth considering a
      decrease in the number of laboratories, with those remaining having the
      possibility of performing STI diagnostic services that are optimised, in
      concordance with international recommendations, standardised, and quality assured
      using systematic internal and external quality controls and systems. In addition,
      establishment of national inter-laboratory networks and reference centres for non
      viral STIs is recommended.

PMID- 29208153
TI  - 'Did you have flu last week?' A telephone survey to estimate a point prevalence
      of influenza in the Swedish population.
AB  - Sentinel surveillance usually underestimates the true burden of influenza in a
      population, as individuals must present to medical establishments to be included
      in the surveillance system. We carried out a telephone survey to estimate the
      national burden of influenza in the Swedish population for one week during the
      2004/05 influenza season. Fixed-line telephone numbers were randomly sampled and
      households interviewed concerning influenza illness between 14-20 February 2005
      (Week 7 of 2005). Questions regarding seasonal influenza vaccination status,
      symptoms and the impact of illness on daily life were also included. A self
      defined influenza prevalence of 7.7% in week 7 of 2005 was estimated. On applying
      a case definition of 'cough and fever and muscle pain' for influenza like
      illness, the prevalence decreased to 3.6%. The survey provided insight into the
      burden of illness in the population further to that estimated through the
      sentinel surveillance system.

PMID- 29208154
TI  - The emergence of LGV in Western Europe: what do we know, what can we do?
AB  - Lymphogranuloma venereum (LGV), a systemic sexually transmitted disease (STD)
      caused by a variety of the bacterium Chlamydia trachomatis, occurs rarely in the
      Western world [1]. However, in January 2004, public health officials in the
      Netherlands noted an outbreak of cases of LGV proctitis among men who have sex
      with men (MSM) [2]. Since then, cases have been reported from several European
      countries, and the United States of America and Canada. In this issue three
      countries report on the current status of LGV [3-5].

PMID- 29208155
TI  - Legionnaires' disease in Europe 2003-2004.
AB  - Once a year, countries that collaborate in the European Surveillance Scheme for
      Travel Associated Legionnaires' Disease (EWGLINET) are requested to submit a
      dataset that provides epidemiological and microbiological information on cases of
      legionnaires' disease (nosocomial (hospital-acquired), community and travel
      related) detected in their country for that year. This paper presents the data
      collected for 2003 and 2004. For this period, 9166 cases were reported to the
      dataset by 35 countries, of which 941 cases were associated with outbreaks.
      Fourteen countries reported a total of 218 detected outbreaks. National infection
      rates varied between countries from 28.7 to less than one case per million
      population. This information is valuable in that it allows countries to assess
      the effectiveness of their national surveillance schemes in detecting cases. Over
      the two year period, 748 cases were reported to have died, giving a case fatality
      rate of 8.2%. The lack of detailed epidemiological information on deaths from
      legionnaires' disease is highlighted. The establishment of the European Centre
      for Disease Prevention and Control is seen as an opportunity to develop European
      collaborations more fully, and to increase further the protection of Europeans
      from outbreaks of legionnaires' disease.

PMID- 29208156
TI  - Epidemic conjunctivitis in Germany, 2004.
AB  - Epidemic conjunctivitis can be associated with viral or bacterial pathogens,
      whereas epidemic keratoconjunctivitis is caused mainly by adenoviruses type 8,19
      and 37. In Germany, the incidence of adenovirus conjunctivitis cases increased
      from 0.2 per 100 000 inhabitants (in 2001 and 2002) eventually to 0.5 in 2003 and
      0.8 in 2004. The detection of adenovirus in conjunctival swabs is notifiable to
      the local health departments. Data about cases with positive conjunctival swabs
      are then transmitted to the Robert Koch-Institut. Quality control of data takes
      place and national surveillance data of confirmed cases with adenovirus
      conjunctivitis are published. From January to April 2004 the national
      surveillance system captured an outbreak with 1024 cases (131 laboratory
      confirmed). Analysis of the national surveillance data showed that in March 2004
      the group primarily affected by epidemic keratoconjunctivitis was young men
      between 18 -29 years old followed by an increased number of notifications from
      women in the same age group. Meanwhile the German Armed Forces experienced an
      outbreak of conjunctivitis, almost exclusively without laboratory confirmation,
      affecting 6378 soldiers. Despite the small number of laboratory confirmed cases
      it became clear from the analysis of the national surveillance data that person
      to-person transmission between young men and similar age groups of the population
      did occur. Whether the outbreak started within the garrisons of the German Armed
      Forces or whether it was triggered within these accommodations, there is clearly
      a need for the national and the military public health institutions to work
      together on guidelines to handle future challenges.

PMID- 29208157
TI  - Using data from a behavioural survey of men who have sex with men (MSM) to
      estimate the number likely to present for HIV pre-exposure prophylaxis (PrEP) in
      Ireland, 2017.
AB  - In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure
      prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition.
      We estimated MSM numbers likely to present for PrEP by applying French PrEP
      criteria to Irish MSM behavioural survey data. We adjusted for survey bias,
      calculated proportions accessing testing services and those likely to take PrEP.
      We estimated 1-3% of MSM in Ireland were likely to present for PrEP.

PMID- 29208158
TI  - HIV testing in Europe: Evaluating the impact, added value, relevance and
      usability of the European Centre for Disease Prevention and Control (ECDC)'s 2010
      HIV testing guidance.
AB  - BACKGROUND: An evaluation of the 2010 ECDC guidance on HIV testing, conducted in
      October 2015-January 2016, assessed its impact, added value, relevance and
      usability and the need for updated guidance. METHODS: Data sources were two
      surveys: one for the primary target audience (health policymakers and decision
      makers, national programme managers and ECDC official contact points in the
      European Union/European Economic Area (EU/EEA) countries and one for a broader
      target audience (clinicians, civil society organisations and international public
      health agencies); two moderated focus group discussions  (17 participants each);
      webpage access data; a literature citation review; and an expert consultation (18
      participants) to discuss the evaluation findings. RESULTS: Twenty-three of 28
      primary target audience and 31 of 51 broader target audience respondents
      indicated the guidance was the most relevant when compared with other
      international guidance. Primary target audience respondents in 11 of 23 countries
      reported that they had used the guidance in development, monitoring and/or
      evaluation of their national HIV testing policy, guidelines, programme and/or
      strategy, and 29 of 51 of the broader target audience respondents reported having
      used the guidance in their work. Both the primary and broader target audience
      considered it important or very important to have an EU/EEA-level HIV testing
      guidance (23/28 and 46/51, respectively). CONCLUSION: The guidance has been
      widely used to develop policies, guidelines, programmes and strategies in the
      EU/EEA and should be regularly updated due to continuous developments in the
      field in order to continue to serve as an important reference guidance in the
      region.

PMID- 29208159
TI  - Reduction in undiagnosed HIV infection in the European Union/European Economic
      Area, 2012 to 2016.
AB  - It is well-documented that early HIV diagnosis and linkage to care reduces
      morbidity and mortality as well as HIV transmission. We estimated the median time
      from HIV infection to diagnosis in the European Union/European Economic Area
      (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a
      decline in the number of people living with undiagnosed HIV in the EU/EEA, many
      remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350
      cells/mm3).

PMID- 29208160
TI  - HIV epidemic among men who have sex with men in the Czech Republic, 2016: high
      time for targeted action.
AB  - Reported incidence of human immunodeficiency virus (HIV) infection in the Czech
      Republic increased steeply over the past decade from 90 new cases in 2005 to 266
      in 2015. This increase is almost exclusively attributed to sexual transmissions
      between men who have sex with men (MSM). In 2015, there were 79% (n=210) newly
      diagnosed cases among MSM, 17% (n=45) were attributed to heterosexual
      transmission and 1% (n=3) to people who inject drugs. Interventions targeted at
      MSM have not yet been prioritised in the broadly focused national HIV prevention
      strategy which this is envisaged to change in the programme set out for 2018 to
      2022. The national budget for HIV prevention has been reduced, however, and this
      remains. Availability of voluntary counselling and testing has decreased
      substantially in the past decade. Post- and pre-exposure prophylaxis for sexual
      intercourse among MSM are not part of the HIV prevention policy and the concept
      of treatment as prevention is not fully recognised. Provision of a combined
      prevention strategy with a focus on MSM, reflecting the above factors including
      stigmatisation, should contribute to reverse the development of a concentrated
      HIV epidemic among MSM in the Czech Republic.

PMID- 29208161
TI  - Hepatitis A outbreak in HIV-infected MSM and in PrEP-using MSM despite a high
      level of immunity, Lyon, France, January to June 2017.
AB  - Since 2016, an increase in the number of hepatitis A cases affecting mainly men
      who have sex with men (MSM) has been reported in low endemic countries in Europe.
      We calculated the attack rate in Lyon, France, in populations considered at high
      risk: HIV-infected MSM and HIV-negative MSM receiving HIV pre-exposure
      prophylaxis (PrEP). In these populations, high level of immunity did not prevent
      the outbreak, indicating that vaccination should be reinforced, particularly in
      younger individuals.

PMID- 29208162
TI  - Healthcare associated infections in university hospitals in Latvia, Lithuania and
      Sweden: a simple protocol for quality assessment.
AB  - Surveillance of healthcare associated infections is an overlooked parameter of
      good clinical practice in most healthcare institutions, due to the workload
      demanded in the absence of adequate IT-systems. The aim of the present study was
      to investigate whether a simple protocol could be used to estimate the burden of
      healthcare associated infections in three university hospitals in Huddinge in
      Sweden, Riga in Latvia and Vilnius in Lithuania and form the basis for initiating
      a long term follow up system. The medical records of all patients receiving
      antibiotics were reviewed according to a standardised protocol, focusing on the
      indications for the drugs and on the frequency of hospital acquired infection
      (HAI) in a point-prevalence survey. Only comparable specialities were included.
      The proportion of patients treated with antibiotics (prophylaxis not included)
      were 63/280 (22%) in Huddinge, 73/649 (11%) in Riga and 99/682 (15%) in Vilnius.
      The proportion of admitted patients treated for a HAI were 15%, 3% and 4%,
      respectively, (both comparisons Huddinge versus other centres P<0.001). Surgical
      site infections were most common, followed by infections with an onset more than
      2 days after admission without any of the other registered risk factors present.
      Our inexpensive and simple method showed that healthcare associated infections
      were a significant problem among patients admitted to Huddinge. The figures
      obtained can be used for further discussion and form a baseline for follow up at
      the local level. The comparison of figures between centres was far less relevant
      than the process the study created.

PMID- 29208164
TI  - Syndromic surveillance based on emergency department activity and crude
      mortality: two examples.
AB  - Recent public health crises have shown the need for readily available information
      allowing proper management by decision-makers. One way of obtaining early
      information is to involve data providers who already record routine data for
      their own use. We describe here the results of a pilot network carried out by the
      InVS (Institut national de veille sanitaire) which gathered data available in
      real time from hospital emergency departments and register offices. Emergency
      departments data were registered from patients' computerised medical files.
      Mortality data were received from the national institute of statistics (Insee).
      Data were transmitted automatically on a daily basis. Influenza data from
      outbreaks in 2004/05 and 2005/06 were compared with data from the sentinel
      network for the same periods. Environmental health data were compared with
      meteorological temperatures recorded in Paris between June and August 2006. A
      mortality analysis was conducted on a weekly basis. Correlation between influenza
      data from emergency departments and data from Sentiweb (sentinel network) was
      significant (p<0.001) for both outbreaks. In 2005 and 2006, the outbreaks were
      described similarly by both sources with identification of the start of the
      outbreaks by both systems during the same weeks. As for data related to heat, a
      significant correlation was observed between some diagnoses and temperature
      increases. For both types of phenomena, mortality increased significantly with
      one to two weeks lag. To our knowledge, this is the first time that a study using
      real time morbidity and mortality data is conducted. These initial results show
      how these data complement each other and how their simultaneous analysis in real
      time makes it possible to quickly measure the impact of a phenomenon.

PMID- 29208163
TI  - Population structure of Escherichia coli O26 : H11 with recent and repeated stx2
      acquisition in multiple lineages.
AB  - A key virulence factor of enterohaemorrhagic Escherichia coli (EHEC) is the
      bacteriophage-encoded Shiga toxin (Stx). Stxs are classified into two types, Stx1
      and Stx2, and Stx2-producing strains are thought to cause more severe infections
      than strains producing only Stx1. Although O26 : H11 is the second most prevalent
      EHEC following O157 : H7, the majority of O26 : H11 strains produce Stx1 alone.
      However, Stx2-producing O26 strains have increasingly been detected worldwide.
      Through a large-scale genome analysis, we present a global phylogenetic overview
      and evolutionary timescale for E. coli O26 : H11. The origin of O26 has been
      estimated to be 415 years ago. Sequence type 21C1 (ST21C1), one of the two
      sublineages of ST21, the most predominant O26 : H11 lineage worldwide, emerged
      213 years ago from one of the three ST29 sublineages (ST29C2). The other ST21
      lineage (ST21C2) emerged 95 years ago from ST21C1. Increases in population size
      occurred in the late 20th century for all of the O26 lineages, but most
      remarkably for ST21C2. Analysis of the distribution of stx2-positive strains
      revealed the recent and repeated acquisition of the stx2 gene in multiple
      lineages of O26, both in ST21 and ST29. Other major EHEC virulence genes, such as
      type III secretion system effector genes and plasmid-encoded virulence genes,
      were well conserved in ST21 compared to ST29. In addition, more antimicrobial
      resistance genes have accumulated in the ST21C1 lineage. Although current
      attention is focused on several highly virulent ST29 clones that have acquired
      the stx2 gene, there is also a considerable risk that the ST21 lineage could
      yield highly virulent clones.

PMID- 29208165
TI  - Hepatitis A vaccination policy for travellers to Egypt in eight European
      countries, 2004.
AB  - In 2004, an outbreak of hepatitis A occurred in European tourists returning from
      Egypt. The reported hepatitis A attack rates varied considerably between tourists
      from different European countries. To determine the reason for this divergence in
      attack rates, a survey was undertaken with the following objectives: (a)
      documentation of national hepatitis A prevention policies for people travelling
      to Egypt and (b) documentation of hepatitis A reporting practices in these
      countries. A questionnaire was compiled and distributed to 13 European countries.
      All eight of the countries that responded had produced guidelines for the
      prevention of travel-associated hepatitis A. Between 2001-2003, 40% (range 4-51)
      of hepatitis A cases reported annually were associated with travel abroad. This
      occurred despite the fact that all countries recommended active vaccination with
      hepatitis A vaccine for people travelling to Egypt for holidays. There was no
      standard case definition for reporting confirmed cases in the countries that
      reported hepatitis A cases. As it is likely that travel-associated infections
      will increase as more people take overseas holidays, innovative ways to increase
      the number of travellers who seek and adhere to appropriate medical advice prior
      to travel must be explored. In addition, we recommend the use of the European
      Commission case definition for notification of confirmed cases of hepatitis A.

PMID- 29208166
TI  - Antibiotic resistance in the southeastern Mediterranean - preliminary results
      from the ARMed project.
AB  - Sporadic reports from centres in the south and east of the Mediterranean have
      suggested that the prevalence of antibiotic resistance in this region appears to
      be considerable, yet pan-regional studies using comparable methodology have been
      lacking in the past. Susceptibility test results from invasive isolates of
      Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Enterococcus
      faecium and faecalis routinely recovered from clinical samples of blood and
      cerebrospinal fluid within participating laboratories situated in Algeria,
      Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey were collected
      as part of the ARMed project. Preliminary data from the first two years of the
      project showed the prevalence of penicillin non-susceptibility in S. pneumoniae
      to range from 0% (Malta) to 36% (Algeria) [median: 29%] whilst methicillin
      resistance in Staphylococcus aureus varied from 10% in Lebanon to 65% in Jordan
      [median: 43%]. Significant country specific resistance in E. coli was also seen,
      with 72% of isolates from Egyptian hospitals reported to be resistant to third
      generation cephalosporins and 40% non-susceptible to fluoroquinolones in Turkey.
      Vancomycin non-susceptibility was only reported in 0.9% of E. faecalis isolates
      from Turkey and in 3.8% of E. faecium isolates from Cyprus. The preliminary
      results from the ARMed project appear to support previous sporadic reports
      suggesting high antibiotic resistance in the Mediterranean region. They suggest
      that this is particularly the case in the eastern Mediterranean region where
      resistance in S. aureus and E. coli seems to be higher than that reported in the
      other countries of the Mediterranean.

PMID- 29208167
TI  - A slow epidemic of LGV in the Netherlands in 2004 and 2005.
AB  - In 2004, an outbreak of LGV was detected in MSM in the Netherlands. By January
      2006, 179 confirmed cases of LGV had been reported; 65 (retrospectively) in
      2002/2003, 76 in 2004 and 38 in 2005. The evolution of the LGV outbreak appears
      to have slowed down and only a few cases were found in the first months of 2006.

PMID- 29208168
TI  - Biochemical evaluation of hydroxyurea derivative schiff bases in liver of rats.
AB  - In this study, it was aimed to examine the antioxidant and antihepatotoxic
      effects of hydroxyurea derivative Schiff bases on serum biochemical parameters
      (AST, ALT, LDH, urea, creatinine and total bilirubin) and antioxidant parameters
      (SOD, CAT, GPx, MDA). In this study, a total of 49 adult male Wistar rats was
      examined and they were divided into 7 equal groups. DMSO, which is diluted only
      with corn oil, was administered to control group. 25 mg / kg ligand, 25 mg / kg
      Schiff base - manganese, 25 mg / kg Schiff base-copper, 25 mg / kg Schiff base -
      zinc, 25 mg / kg Schiff base - nickel, 25 mg / kg Schiff base - cobalt complexes
      were administered to rats of experimental group subcutaneously for 15 days with
      three-day intervals throughout the test process. All specimens were killed by
      decapitation and their livers were extracted. According to the results obtained,
      ALT level was observed to be higher (P<0.05) in the Cu-L group compared to other
      groups. LDH level was observed to be higher (P<0.05) in the Cu-L and Co-L groups
      compared to other groups. SOD level was observed to be higher (P<0.05) in the Cu
      L, Mn-L and Zn-L groups compared to other groups. MDA level was observed to be
      higher (P<0.05) in the Ni-L, Cu-L, Zn-L groups compared to other groups. In
      conclusion, it can be suggested that the determination of the pharmacological
      characteristics of them can be beneficial in numerous fields of application
      thanks to the antioxidant and hepatotoxic activities demonstrated by hydroxyurea
      derivative Schiff bases.

PMID- 29208169
TI  - Effect of melatonin on cytokine levels in a hyperthermia-induced febrile seizure
      model.
AB  - Higher serum cytokine levels have been reported in children admitted with febrile
      seizures and in some experimental models. However, other studies have shown that
      cytokine levels are influenced by melatonin. In this study, we investigated serum
      cytokine levels in a hyperthermia-induced febrile rat seizure model and the
      effect of melatonin. A total of 28 male Sprague-Dawley rats were divided into
      four groups: the control (C) group, healthy melatonin (MT) group, and
      hyperthermia-induced febrile seizure groups with (HIFS-MT) and without (HIFS)
      administration of melatonin. Melatonin (80 mg/kg) was given intraperitoneally 15
      min before the seizure. HIFS was induced by placing the rats in 45 degrees C
      water. The rats were sacrificed under anesthesia after the seizure. Blood samples
      were drawn by transcardiac puncture to measure serum cytokine and melatonin
      levels. Serum interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor
      (TNF)-alpha levels were lower in the HIFS group than those in the C group (p =
      0.005, p = 0.200, p = 0.011, and p = 0.016, respectively). All serum cytokine
      levels of rats in the MT and HIFS-MT groups were similar to those in the C group.
      This experimental rat model demonstrated that serum cytokine levels decrease with
      HIFS and that administering melatonin maintains serum cytokine levels. These
      results suggest that cytokines may play role in the anticonvulsive activity of
      melatonin in rats with febrile seizures.

PMID- 29208170
TI  - Ferula gummosa gum induces apoptosis via ROS mechanism in human leukemic cells.
AB  - Ferula species known for its oleo-resins that are recognized valuable industrial
      crops and food products. In this study, we examined the level of cellular
      oxidants, cytotoxicity, apoptosis and differentiation induced by oleo resin gum
      from Ferula gummosa (30-250 ug/mL), as well as Arsenic trioxide (50 uM, as
      positive control), in leukemic (NB4 and HL-60 cells) and normal polymorph nuclear
      cells during 72 h. Resazurin assay was used to determine cell viability following
      treatment with F. gummosa (30-250 ug/mL). Intracellular reactive oxygen species
      was measured by fluorimetry using carboxy 2', 7'-dichlorofluorescein diacetate.
      Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow
      cytometry (sub-G1 peak). Differentiation of cells evaluated by Giemsa staining
      and Nitro Blue Tetrazolium reduction. F. gummosa showed a concentration-dependent
      suppression in cell survival with IC50 values of 41.8 ug/mL for HL60 and 59.2
      ug/mL for NB4 cells after 72 h treatment. ROS formation and apoptotic cells were
      concentration-dependently increased following treatment with F. gummosa, similar
      to As2O3. F. gummosa did not induce differentiation of leukemic cells towards
      granulocytic pattern. The resin did not have toxic effect on PMN cells (<800
      ug/mL). In conclusion, the present study demonstrated that F. gummosa induced
      apoptosis through ROS mechanism on leukemic cells as a concentration and time
      dependent manner. The precise signaling pathway by which F. gummosa induce
      apoptosis needs further research.

PMID- 29208171
TI  - Ecological and biological studies on five-lined skink, Trachylepis (= Mabuya)
      quinquetaeniata inhabiting two different habitats in Egypt.
AB  - This study was carried out to study the diet type, genetic, morphometric and
      histological variations between two natural populations of Trachylepis
      quinquetaeniata inhabiting Abu-Rawash, Embaba, North Giza and Garfas-Senoures, El
      Faiyum habitats. In this study, morphometric examination showed that Trachylepis
      quinquetaeniata is a typically ground-dwelling Skink and seems to be frequently
      associated with grass and below shrubs. Geographic variation in sexual size
      dimorphism (SSD) and head size dimorphism (HSD) with greater dimensions in Garfas
      Senoures, El-Faiyum compared with Abu-Rawash, Embaba, North Giza might be
      correlated with spatial food availability and abundance or micro-evolutionary
      change or phenotypic plasticity. Also, the increase of body size and mass in
      individuals from Garfas-Senoures, El-Faiyum might be an adaptation to lower
      ambient temperature and hypoxia. Diet analysis showed that the bulk of gut
      contents were beetles, plant bugs, hymenopterans and dipterans. The remainder of
      the plant material was probably ingested secondarily. Moreover, the increase in
      the activity of Ldh in liver tissues of T. quinquetaeniata inhabiting Abu-Rawash,
      Embaba, North Giza could be confirmed by the significant increase in the
      accumulation of the total lipids in liver and muscle tissues than that in the
      other population. As well as, a marked degeneration, necrosis and desquamation of
      spermatogoneal cells lining seminiferous tubules in testes of T. quinquetaeniata
      inhabiting Garfas-Senoures, El-Faiyum than that in the other population
      inhabiting Abu-Rawash, Embaba, North Giza that could be attributed to the
      bioaccumulation of soil heavy metals in testes. Higher carbohydrate accumulation
      in the former lizards' population was confirmed by the high availability and
      diversity of diet in El-Faiyum habitat. Thus we concluded that T. quinquetaeniata
      inhabiting Abu-Rawash, Embaba, North Giza is more active, energetic and adaptable
      in its habitat than T. quinquetaeniata inhabiting Garfas-Senoures, El-Faiyum.

PMID- 29208172
TI  - Investigation of role of vascular endothelial growth factor, Annexin A5 and
      Apelin by immunohistochemistry method in placenta of preeclampsia patients.
AB  - Preeclampsia is a disease characterized by hypertension and proteinuria occurred
      after 20 weeks of gestation. Preeclampsia is a major cause of maternal and fetal
      morbidity and mortality.  The pathophysiological mechanism of preeclampsia is not
      known exactly yet. Preeclampsia endothelial cell dysfunction, associated with
      inadequate trophoblastic invasion is characterized by abnormal placentation.
      Vascular endothelial growth factor (VEGF) according to is an angiogenic cytokine,
      Annexin A5 is among endogenous peptides are both expressed from placental
      trophoblasts and Apelin is a multifunctional peptide and expressed by placental
      trophoblasts and endothelial cells. It was aimed to investigate roles of these
      parameters occurring in preeclampsia and to compare immunoreactivity of them in
      normal and preeclamptic placenta. In this study, placentas were collected from 20
      normotensive pregnant women as controls, 16 mild-preeclamptic pregnant women, and
      16 severe preeclamptic women. VEGF, Annexin A5 and Apelin were examined in
      samples of placenta tissues by streptavidin-biotin-peroxidase complex
      immunohistochemical methods. Immunoreactivity scores (IRS) were obtained for each
      parameter.  VEGF and Apelin IRS were increased significantly in preeclamptic
      groups compared with control group (p <0.026, p<0.002 respectively). But Annexin
      A5 IRS was decreased significantly in preeclamptic groups compared with control
      group (p<0.04). In correlation with the intensity of disease, increase in VEGF
      and Apelin, and decrease in Annexin A5 supports roles of hemo-dynamic alterations
      in fetoplacental circulation and structural alterations in uteroplacental bed
      occurring in preeclampsia.

PMID- 29208173
TI  - Transforming Growth Factor-beta1 gene polymorphism and osteoporosis in
      postmenopausal egyptian women.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a wide spread bone matrix protein
      that affect the function, formation and cell-cell interactions of osteoclasts and
      osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim
      of this study is to evaluate the role of the two polymorphism of transforming
      growth factor-beta1 T869C and C-509T in developing osteoporosis in postmenopausal
      Egyptian women. This study was performed on 138 postmenopausal
      osteoporosis/osteopenic women and 128 postmenopausal female control group. There
      was a significant statistical difference in the CC, CT and TT (T869C) genotype
      frequencies between the osteopenia/osteoporosis and control subjects (p value
      <0.001). There was a non-significant statistical difference in the CC, CT and TT
      (T-509C) genotype frequencies between the osteopenia/osteoporosis and control
      subjects (p value <0.082). There was a significant statistical difference between
      TT,CT and CC of (T869C) and T score, Z score and calcium of
      osteopenia/osteoporosis group (p value <0.001). There was a non-significant
      statistical difference between TT, CT and CC of (T-509C) and T score, Z score of
      osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically
      significant difference between the three genotyping and serum calcium and
      creatinine (p value 0.04). Multivariate regression analysis showed that T869C
      polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57,
      95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-beta1 gene
      has an impact on bone mineral density and enhancement of the susceptibility to
      osteopenia/osteoporosis in Egyptian women.

PMID- 29208174
TI  - Strong antimicrobial activity of Hypericum perforatum L. against oral isolates of
      Lactobacillus spp.
AB  - Lactobacillus spp. are one of the first microorganisms involved in the
      development of dental caries in the first years of life of the child. The purpose
      of this study was to investigate the antibacterial effect of alcoholic extract of
      hypericin against strains of Lactobacillus spp. and determine its related MIC
      (minimum inhibitory concentration); and cytotoxic effect against gingival
      fibroblasts. Antimicrobial activity and MIC were evaluated using micro broth
      dilution method based on CLSI (clinical and laboratory standards institute)
      protocols. Determination of cytotoxicity was done by using MTT assay protocol on
      gingival fibroblast cells at 24, 48 and 72 hours after adding different
      concentrations of alcoholic extract of hypericin. Hypericin extract had an
      antimicrobial effect on lactobacillus spp., and its MIC was determined to be
      0.625ug/ml . The IC50 value after 24, 48 and 72 hours was obtained as 0.89MUg/ml,
      0.7MUg/ml and 0.604MUg/ml, respectively. Hypericin extract MIC for L.acidophilus
      spp. was 0.625ug/ml and given that, MIC was less than IC50. This concentration
      does not have toxic effects on gingival fibroblast cells. The results of this
      study indicate that hypericin extract was able to eliminate acid producing
      strains in the mouth and can be evaluated as a suitable and safe substitute for
      mouthwashes and oral disinfectants.

PMID- 29208175
TI  - Antifungal activity of silver nanoparticles on Fluconazole resistant
      Dermatophytes identified by (GACA)4 and isolated from primary school children
      suffering from Tinea Capitis in Ismailia - Egypt.
AB  - Fungal infections caused by dermatophytes recently became more common. Available
      antifungal drugs are limited because of emergence of resistant strains due to
      prophylaxis with them, so there is an urgent need for novel antifungals. This
      study is aimed to detect the antifungal activity of silver nanoparticles (SNPs)
      on Fluconazole resistant dermatophytes isolated from primary school children
      clinically suffering from tinea capitis and attending El-Sheikh Zaid Dermatology
      Center in Ismailia. The study was done on 112 clinical cases. Examination with
      potassium hydroxide(KOH) of hair samples was done, followed by routine
      identification using culturing, macroscopical and microscopical examination and
      biochemical tests, finally molecular identification using Polymerase Chain
      Reaction (PCR) with (GACA) 4 was done. Fluconazole resistance of these
      dermatophytes was detected by different methods including agar disc diffusion
      method and broth microdilution susceptibility testing. Silver nanoparticles
      susceptibility testing was carried out on these Fluconazole resistant
      dermatophytes. The Ubiquitin 1 (Ub 1) gene was detected in samples which were
      Fluconazole resistant but SNPs susceptible. In this study dermatophytes were
      found only in 70 samples (62.5%). They were belonged to 3 species: Trichophyton
      violaceum, Microsporum gypseum and Microsporum canis. Fluconazole resistance was
      found in 58 samples (82.85%). Both M. canis and M. gypseum were resistant to all
      used concentrations of SNPs, while T. violaceum was susceptible to 50 ug/ml SNPs
      solution. The Ub1 gene was detected in 1 sample (4.8%). Therefore SNPs can be
      used for treatment of T. violaceum, while they can't be used for treatment of M.
      canis or M. gypseum.

PMID- 29208176
TI  - Analysis of potential interactions between vitamins D and C using gene expression
      profiles from mouse models.
AB  - Vitamin D (VD) and vitamin C (VC) have been recognized as essential elements for
      human health.  Animal models, especially mouse models, have been widely used in
      the study of VD and VC. This study is to investigate how VD and VC interact at
      molecular level using whole genome expression profiles from spleens of 111 mouse
      strains and livers from 40 mouse strains. We first identified the genes that are
      closely correlated to vitamin D receptor (Vdr) and gulonolactone oxidase (Lgo).
      We next analyzed the potential molecular pathways of Vdrand Lgo correlated genes
      and examined how these two sets of pathways are connected in liver and spleen.
      Our results indicated that Vdrand Lgo associate to distinct groups of genes.
      While most of genes are not the same, a few of them are associated to both Vdrand
      Lgo.  Our gene network construction suggests that there are interactions between
      Vdrand Lgopathways.  Our work laid down the foundation for future study of the
      interactions between VD and VC and revealed the potential bias when using animals
      for the study of VD or VC, as humans do not produce VC.

PMID- 29208177
TI  - Human haematological and epithelial tumor-derived cell lines express distinct
      patterns of onco-microRNAs.
AB  - MicroRNAs post-transcriptionally regulate gene expression thus playing a critical
      role in a wide range of physiological and pathological processes, including
      cancer initiation and progression. Moreover, a growing number of evidences
      highlights that miRNAs themselves are differentially expressed between normal and
      malignant tissues. In this study, we analysed differences in miRNA expression
      profile between haematological and epithelial tumor-derived cell lines and
      explored their role in definying different cancer cells phenotypes. Cancer Focus
      microRNA PCR Panel was used to analyze eighty-four oncomiRNAs in two human
      haematological (K562 and HL-60) and in two epithelial (H460 and MCF-7) cancer
      cell lines. Bioinformatic tools were used to identify miRNA-specific signatures
      and to discover potentially deregulated pathways. Our analysis led to the
      identification of i) a large repertoire of miRNAs commonly expressed in the four
      cell lines, including two equally highly expressed (UPmiRs) and four equally low
      expressed (DNmiRs); ii) two miRNAs signatures, one associated with the
      haematological and one with the epithelial cell lines; iii) miRNA signatures
      specific for the acute or for the chronic myeloid leukemic cells; iv) miRNA
      signatures specific for the lung or for the breast carcinoma cells. As a whole,
      these results strengthen the significance of miRNAs profiling in human cancer
      subtyping, providing the ground for the identification of novel potential
      biomarkers for specific cancer cell phenotypes.

PMID- 29208178
TI  - Bioactive flavones isolated from Tunisian Artemisia campestris L. Leaves.
AB  - Four flavones were isolated from dried leaves of Artemisia campestris L.
      2',4',5,7-tetrahydroxy-5',6-dimethoxyflavone, eupatilin and dimethoxycentaureidin
      were reported for the first time in this species whereas cirsiliol was previously
      identified but it was isolated for the first time. Their structures were
      elucidated by spectroscopic methods, including 1D and 2D NMR experiments and mass
      spectrometry analysis. In addition, all isolated flavones were evaluated for
      their antioxidant, anti-inflammatory, anti-superoxide dismutase, anti-xanthine
      oxidase and cytotoxic activities. The results showed that all isolated compounds
      exhibited potent anti-xanthine oxidase activity with IC50 ranging from 3.3 to 6.8
      uM, which was higher than that of the control compound allopurinol (8.2 +/- 0.6
      uM). In addition, cirsiliol was found to be the most cytotoxic against OVCAR-3,
      IGROV-1and HCT-116 cell lines at 15uM, with inhibition percentage values of 53.7,
      48.8 and 40.9%, respectively. All compounds also showed weak to moderate anti
      inflammatory and anti-superoxide dismutase activities.

PMID- 29208179
TI  - Genetic characterization and assessment of demographic bottleneck in Caspian
      horse population.
AB  - The aim of this study was to evaluate genetic characterization of the Caspian
      horse population using microsatellite markers. This study determined the
      efficiency of microsatellite markers for conservation plans and breeding
      strategies in Caspian horse population. For this purpose, 120 Caspian horse
      samples including 95 adults and 25 foals were genotyped by using seventeen
      microsatellite markers recommended by ISAG. The number of allele per locus varied
      from 5 (HMS01 and HTG07) to 9 (HTG10) with an average value of 7.41. The observed
      heterozygosity and the expected heterozygosity ranged 0.505-0.831 (mean 0.684),
      from 0.615-0.835 (mean 0.748) respectively. PIC value ranged from 0.716 (HMS01)
      to 0.834 (AHT04) with average 0.787. The total exclusion probability of the 17
      microsatellite loci was 0.9999. Low values of Wright's fixation index, Fis
      (0.084) indicated low levels of inbreeding. A significant heterozygote excess on
      the basis of different models suggested that Caspian horse population has
      decreased to low numbers in the past, but a bottleneck event is still scrutable,
      and its number has recently increased is not in mutation drift equilibrium. The
      present study contributes to our knowledge of the genetic diversity of the
      Caspian horse population and helps to define its genetic conservation strategies.

PMID- 29208180
TI  - Curcumin induce DNA damage and apoptosis through generation of reactive oxygen
      species and reducing mitochondrial membrane potential in melanoma cancer cells.
AB  - Melanoma is the most malignant skin cancer. Curcumin has shown to have
      therapeutic effects when used in the treatment of malignant diseases. However,
      the precise molecular mechanisms of its action are not fully elucidated. In this
      research, we hypothesized that reactive oxygen species (ROS) play a key role in
      curcumin induced DNA damage, apoptosis and cell dead. To test our hypothesis,
      cytotoxic, genotoxic, apoptotic, ROS generating and mitochondrial membrane
      potential (MMP) of curcumin on mouse melanoma cancer cells (B16-F10) and
      fibroblastic normal cells (L-929) were investigated. Our results demonstrated
      that curcumin decreased cell viability and MMP and, increased DNA damage,
      apoptosis and ROS levels in both melanoma cancer and normal cells in a dose
      dependent manner and, these activities were significantly higher in melanoma
      cells than in normal cells with higher concentrations. There were positive strong
      relationships between DNA damage, apoptosis, cytotoxicity and ROS generation and
      MMP levels in curcumin treated melanoma and normal cells.  In summary, this in
      vitro study provide clear evidence that curcumin induced DNA damage, apoptosis 
      and cytotoxicity via its pro-oxidant activity in a dose dependent manner in both
      cancer and normal cells and these activities were higher in cancer cells than
      those of normal cells.

PMID- 29208181
TI  - Potential biomarkers for the diagnosis of respiratory tract infection and lungs
      cancer.
AB  - Major hurdle faced by many physicians in treating various respiratory tract
      infections and lung carcinomas is their late or mis-diagnosis. In most
      respiratory tract infections the manner of infection is not completely
      understood. Similarly, various lung carcinomas are diagnosed at advance stages at
      which not only the treatment possibilities are narrowed but the chances of
      survival are also reduced. So, for the sake of better treatment, the quick and
      improved diagnostic strategies are suggested. Protein biomarkers fully fit the
      description in this regard as they have shown great potential in specific
      diagnosis of many respiratory diseases and also have shown capability in timely
      pin pointing different stages of lung carcinomas. Many serum biomarkers are
      presently being used for diagnosis but the efficiency for diagnosis of these
      biomarkers is lower when used alone. So, physicians are suggested to use the
      combination of different biomarkers. Moreover, genetic biomarkers are also
      currently studied to indicate the exact stage of disease, the possible damage
      occurred, the severity of disease and also for the analysis of the possible body
      response to the therapeutics.

PMID- 29208182
TI  - Complexity of phenotypes induced by p.Asn1303Lys-CFTR correlates with difficulty
      to rescue and activate this protein.
AB  - Cystic Fibrosis is the most common recessive autosomal rare disease found in
      Caucasian. It is caused by mutations on the Cystic Fibrosis Transmembrane
      Conductance Regulator gene (CFTR) that encodes for a protein located on the
      apical membrane of epithelial cells. c.3909C>G (p.Asn1303Lys) is one of the most
      common worldwide mutations located in nucleotide binding domain 2. The effect of
      the p.Asn1303Lys mutation on misprocessing was studied by immunofluorescence and
      western blotting analysis in presence and absence of treatment. To evaluate the
      functionality of potentially rescued p.Asn1303Lys-CFTR, we assessed the channel
      activity by radioactive iodide efflux. No recovery of the activity was observed
      in transfected cultured cells treated with VX-809. Thus, our results suggest that
      multiple drugs may be needed for the treatment of c.3909C>G patients in order to
      correct and activate p.Asn1303Lys-CFTR as it shows folding and functional
      defects.

PMID- 29208183
TI  - Promoter motifs required for c-mpl gene expression induced by thrombopoietin in
      CMK cells.
AB  - Thrombopoietin (TPO) and its receptor, c-Mpl, are the central regulators of
      megakaryocyte development and platelet production and are also crucial to
      regulate megakaryocytopoiesis. TPO remarkably elevated c-mpl promoter activity,
      while the protein kinase C (PKC) inhibitors, GF109203, H7 and Calphostin C,
      clearly reduced the steady level of its promoter activity.  In the present study,
      motifs crucial for c-mpl promoter activity induced by TPO treatment have been
      analyzed using a human megakaryoblastic cell line, CMK. Destruction of the 
      107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in
      decrease of the promoter activity by 53.1% and 64.4%, respectively, and
      destruction of -69Ets and -28Ets elements dramatically decreased the promoter
      activity by 96.4% and 87.8%, respectively, while mutation of -77GATA moderately
      reduced the activity by 31.4%. The result was in agreement with our previous
      report that showed the crucial motifs in the c-mpl promoter for the promoter
      activity induced by PMA-treatment. This indicates that TPO-induced activation of
      the c-mpl promoter activity is fully modulated by transcription through a PKC
      dependent pathway and the two Sp1 and two Ets motifs are crucial for the
      activation of the c-mpl promoter activity rather than a GATA motif in the c-mpl
      promoter of CMK cells.

PMID- 29208184
TI  - Development of PCR primer systems for amplification of 16S-rDNA to detect of
      Thiobacillus spp.
AB  - Thiobacillus is a genus of Gram-negative, rod-shaped and autotrophic
      Betaproteobacteria. They catalyze the dissimilatory oxidation of elemental sulfur
      and reduced inorganic sulfur compounds. Whereas more than 30 species have been
      known in this genus, most were never reliably or effectively published. The rest
      were either reclassified into Thiomonas, Paracoccus, Starkeya, Sulfuriferula,
      Halothiobacillus, Thermithiobacillus or Acidithiobacillus, were lost from
      culture. Most of Thiobacillus species are obligate autotrophs via elementary
      sulfur, thiosulfate or polythionates as energy sources. Based on 16S ribosomal
      RNA sequence analysis, many members of Thiobacillus have been reclassified. A
      system was developed for the detection of Thiobacillus bacteria by the
      amplification of specific 16S ribosomal RNA sequence gene (16S rDNA) fragments
      with PCR. Primer sequences were designed for the amplification of fragments of
      16S rDNA.

PMID- 29208185
TI  - Association between vitamin D receptor BsmI gene polymorphism and periodontitis:
      a meta-analysis in a single ethnic group.
AB  - Although many researchers have studied on the association between vitamin D
      receptor (VDR) BsmI polymorphism and periodontitis, this association remains
      elusive. To further assess the effects of VDR BsmI polymorphism on the risk of
      periodontitis, a meta-analysis was performed in a single ethnic group. We
      searched PubMed and Chinese databases for relevant studies till April 2017. The
      strength of the associations were assessed used pooled odds ratios (ORs) and 95%
      confidence intervals (CIs). Six studies including 757 periodontitis cases and 670
      controls were identified at last. In the total analyses, VDR BsmI polymorphism
      was not associated with the risk of periodontitis in all models. The subgroup
      analyses suggested a significantly reduced risk of periodontitis in South China.
      In conclusion, our meta-analysis showed that VDR BsmI polymorphism was associated
      with the decreased risk of periodontitis in Chinese individuals from South China,
      and further studies in other ethic groups are required for definite conclusions.

PMID- 29208186
TI  - Association between platelet glycoprotein Ia C807T gene polymorphism and ischemic
      stroke: a meta-analysis in a separate ethnic group.
AB  - Many studies have been examined the association of platelet glycoprotein (GP) Ia
      C807T polymorphism with ischemic stroke (IS) susceptibility. However, the results
      of these studies are inconsistent. To further assess the effects of GP Ia C807T
      polymorphism on the risk of IS, a meta-analysis was performed in a separate
      ethnic group. Relevant studies were identified using PubMed and Chinese databases
      through January 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs)
      were used to assess the strength of the associations. Finally, 13 studies
      contained 2438 IS cases and 2308 controls included. In the total analyses, a
      significantly elevated risk of IS was associated with all variants of GP Ia C807T
      in the Chinese population (T vs C: OR = 1.24, 95% CI = 1.09-1.40; TT vs CC: OR =
      1.59, 95% CI = 1.17-2.15; TT and CT combined vs CC: OR = 1.32, 95% CI = 1.09
      1.59; TT vs CC and CT: OR = 1.35, 95% CI = 1.04-1.76). In the subgroup analyses
      stratified by ethnicity and geographic areas, it revealed the significant results
      in Chinese Han and in South China. This meta-analysis provides the evidence that
      GP Ia C807T polymorphism may contribute to the IS development in the Chinese
      population, especially in South China, and further studies in other ethic groups
      are required for definite conclusions.

PMID- 29208187
TI  - A meta-analysis study of the association between EGFR rs2252586 mutation and the
      risk of glioma.
AB  - Several studies reported the association between Epidermal growth factor receptor
      (EGFR) rs2252586 mutation and glioma susceptibility. However, the results of
      these studies were inconsistent. A computer-based search using EMBASE and PubMed
      databases was conducted. Odds ratios (OR) and 95% confidence interval (CI) were
      used to assess the strength of association between EGFR rs2252586 mutation and
      glioma susceptibility. The EGFR rs2252586 mutation was significantly associated
      with an increased risk of glioma (OR=1.16; 95%CI, 1.11-1.21; P<0.00001). When
      stratified by tumor subtype, the significantly elevated risk was observed in
      glioblastoma (OR=1.15; 95%CI, 1.04-1.26; P=0.007) but not in oligodendroglioma
      (OR=1.19; 95%CI, 0.97-1.46; P=0.10). When we excluded the studies with small
      sample size (case number < 1000), a significant association between EGFR
      rs2252586 mutation and glioma susceptibility remained (OR=1.16; 95%CI, 1.09-1.22;
      P<0.00001). In conclusion, this meta-analysis found that EGFR rs2252586 mutation
      was significantly associated with glioma risk.

PMID- 29208188
TI  - The antiosteoporosis effect of icariin in ovariectomized rats: a systematic
      review and meta-analysis.
AB  - Herba Epimedii (Yinyanghuo or Horny Goat Weed) is a traditional Chinese medicine
      widely used in treating osteoporosis. As the major active component, icariin is
      intensively investigated in the prevention and treatment of osteoporosis in
      ovariectomized rats. However, misleading conclusions can be generated in animal
      studies with various experimental designs. Therefore, a systematic review and
      meta-analysis was performed to evaluate the efficacy of icariin against
      osteoporosis in ovariectomized rats. PubMed, EMBASE and Chinese National
      Knowledge Infrastructure databases were searched to identify studies of icariin
      in ovariectomized rats. Two independent authors selected and reviewed the
      publications. Data were pooled using a DerSimonian and Laird random-effects
      model. The results demonstrated that ovariectomized rats treated with icariin had
      significantly higher bone mineral density (femur and lumbar spine) and lower bone
      turnover markers (serum alkaline phosphatase and osteocalcin) compared with the
      ovariectomized control group. For bone histomorphometric parameters, the
      percentages of trabecular area and trabecular thickness were significantly higher
      while the trabecular separation was significantly lower in the ovariectomized
      rats treated with icariin. Based on these results, the presnet study suggested
      that icariin might possess substantial antiosteoporosis effect in ovariectomized
      rats. Safety studies and large randomized clinical trials are needed to further
      support possible clinical applications of icariin in postmenopausal women with
      osteoporosis.

PMID- 29208189
TI  - Enlightenment and lesson from the successful treatment of acute superior
      mesenteric artery embolism.
AB  - Despite recent advances, treatment of acute superior mesenteric artery embolism
      (SMAE) in emergency is still very difficult. The comparative rarity, the
      difficulty of early diagnosis, and the extremely high mortality of SMAE give us
      the sufficient reasons to report our successful experience in curing a patient
      with acute SMAE. In the present case, the patient was diagnosed early without
      evidence of intestinal necrosis. The diagnosis of SMAE was verified by computed
      tomography angiography (CTA). A comprehensive treatment was immediately employed
      including a combination of intra-arterial thrombolysis and embolectomy operation
      with emergent laparotomy. We summarize that the successful treatment of superior
      mesenteric artery embolism depends on early diagnosis and timely reestablishment
      of arterial flow under the support of general treatments such as prevention of
      sepsis and control of organic insufficiencies. Through a combined treatment,
      patient's life could be saved without complications.

PMID- 29208191
TI  - [Throat pain after colonoscopy].
AB  - A 38-year-old man known with inflammatory bowel disease, received an ileostomy
      and a blinded colon. Eight years later the patient underwent a painful
      colonoscopy, performed under suspicion of malignancy in the blinded colon. Two
      days later the patient was admitted due to hoarseness, throat pain and a feeling
      of neck swelling but no abdominal pain. A chest X-ray showed subcutaneous
      emphysema in the neck region and pneumoperitoneum. We conclude, that
      colonoscopies can give a variety of complications, such as perforation in the
      colon with secondary subcutaneous emphysema in the neck and throat region.

PMID- 29208192
TI  - [A 12-kg benign ovarian tumour in a teenage girl].
AB  - This is case report of a 14-year-old girl with severe abdominal swelling over a
      period of 12 months. The patient was admitted to the local children's hospital,
      and an ultrasound scan was performed. The scan showed a tumour in the right
      ovary. Further investigation with MRI confirmed the tumour as cystic, and
      resection and pathological examination revealed a 12-kg benign cystadenoma of the
      right ovary.

PMID- 29208193
TI  - [Epidermolysis bullosa].
AB  - Epidermolysis bullosa (EB) is a rare genodermatosis. A new classification system
      is presented, distinguishing the subtypes of EB, and this system is based on the
      phenotype, mode of inheritance, ultrastructure, immunofluorescence findings, and
      specific mutation(s) present. EB is inherited in an autosomal dominant or 
      recessive fashion. Clinical manifestations vary in severity and character
      according to subtype. The severity ranges from mild localized to life
      threatening. Available treatment is mainly symptomatic with therapeutic treatment
      in an experimental stage.

PMID- 29208190
TI  - Preventing blood-borne virus infection in people who inject drugs in the UK:
      systematic review, stakeholder interviews, psychosocial intervention development
      and feasibility randomised controlled trial.
AB  - BACKGROUND: Opioid substitution therapy and needle exchanges have reduced blood
      borne viruses (BBVs) among people who inject drugs (PWID). Some PWID continue to
      share injecting equipment. OBJECTIVES: To develop an evidence-based psychosocial
      intervention to reduce BBV risk behaviours and increase transmission knowledge
      among PWID, and conduct a feasibility trial among PWID comparing the intervention
      with a control. DESIGN: A pragmatic, two-armed randomised controlled, open
      feasibility trial. Service users were Steering Group members and co-developed the
      intervention. Peer educators co-delivered the intervention in London. SETTING:
      NHS or third-sector drug treatment or needle exchanges in Glasgow, London,
      Wrexham and York, recruiting January and February 2016. PARTICIPANTS: Current
      PWID, aged >= 18 years. INTERVENTIONS: A remote, web-based computer randomisation
      system allocated participants to a three-session, manualised, psychosocial,
      gender-specific group intervention delivered by trained facilitators and BBV
      transmission information booklet plus treatment as usual (TAU) (intervention), or
      information booklet plus TAU (control). MAIN OUTCOME MEASURES: Recruitment,
      retention and follow-up rates measured feasibility. Feedback questionnaires,
      focus groups with participants who attended at least one intervention session and
      facilitators assessed the intervention's acceptability. RESULTS: A systematic
      review of what works to reduce BBV risk behaviours among PWID; in-depth
      interviews with PWID; and stakeholder and expert consultation informed the
      intervention. Sessions covered improving injecting technique and good vein care;
      planning for risky situations; and understanding BBV transmission. Fifty-six per
      cent (99/176) of eligible PWID were randomised: 52 to the intervention group and
      47 to the control group. Only 24% (8/34) of male and 11% (2/18) of female
      participants attended all three intervention sessions. Overall, 50% (17/34) of
      men and 33% (6/18) of women randomised to the intervention group and 47% (14/30)
      of men and 53% (9/17) of women randomised to the control group were followed up 1
      month post intervention. Variations were reported by location. The intervention
      was acceptable to both participants and facilitators. At 1 month post
      intervention, no increase in injecting in 'risky' sites (e.g. groin, neck) was
      reported by participants who attended at least one session. PWID who attended at
      least one session showed a trend towards greater reduction in injecting risk
      behaviours, a greater increase in withdrawal planning and were more confident
      about finding a vein. A mean cost of L58.17 per participant was calculated for
      those attending one session, L148.54 for those attending two sessions and L270.67
      for those attending all three sessions, compared with L0.86 in the control group.
      Treatment costs across the centres vary as a result of the different levels of
      attendance, as total session costs are divided by attendees to obtain a cost per
      attendee. The economic analysis suggests that a cost-effectiveness study would be
      feasible given the response rates and completeness of data. However, we have
      identified aspects where the service use questionnaire could be abbreviated given
      the low numbers reported in several care domains. No adverse events were
      reported. CONCLUSIONS: As only 19% of participants attended all three
      intervention sessions and 47% were followed up 1 month post intervention, a
      future definitive randomised controlled trial of the intervention is not
      feasible. Exposure to information on improving injecting techniques did not
      encourage riskier injecting practices or injecting frequency, and benefits were
      reported among attendees. The intervention has the potential to positively
      influence BBV prevention. Harm reduction services should ensure that the
      intervention content is routinely delivered to PWID to improve vein care and
      prevent BBVs. FUTURE WORK: The intervention did not meet the complex needs of
      some PWID, more tailoring may be needed to reach PWID who are more frequent
      injectors, who are homeless and female. LIMITATIONS: Intervention delivery proved
      more feasible in London than other locations. Non-attendance at the York trial
      site substantially influenced the results. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN66453696 and PROSPERO 014:CRD42014012969. FUNDING: This project was
      funded by the National Institute for Health Research Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 21,
      No. 72. See the NIHR Journals Library website for further project information.

PMID- 29208194
TI  - [Gut microbiota and depressive symptoms].
AB  - The gut microbiota is believed to affect a wide variety of mental disorders,
      including depression. The hypothesis involves bacterial signalling to the host
      through metabolic, endocrinal, immunologic and neuronal pathways. Few studies of
      patients with depression have shown altered microbiota profiles and increased
      levels of systemic endotoxin, which can be detected by leucocytes and result in
      expression of cytokines. Studies performed so far have lacked statistical power
      and provide no causal explanation for the gut-brain hypothesis. Further research
      into the matter is certainly warranted.

PMID- 29208195
TI  - [Treatment principles in bone reconstruction and limb lengthening of the lower
      extremity].
AB  - Limb length discrepancies, axis deviations and bone loss on a congenital,
      traumatic or infectious basis are treated with restoration of axis and bone
      elongation. The intention is to improve gait and function, to relieve pain caused
      by imbalance in the musculoskeletal system and to prevent degenerative joint
      disease. Modern motorized intramedullary nails spare the patients for external
      fixators, and thus complications are being reduced. X-ray, CT-based planning and
      a thorough clinical examination is essential for a good result. Complications are
      frequent, and treatment can be lengthy. Modern techniques have made treatment
      more gentle and allow a normal daily life during treatment and rehabilitation.

PMID- 29208196
TI  - ?

PMID- 29208197
TI  - [Treatment of rolandic epilepsy].
AB  - Recent literature indicates, that rolandic epilepsy/epilepsy of childhood with
      centrotemporal spikes may not be as benign as previously assumed. This study
      investigates the existing evidence, which describes the treatment effects on
      seizure frequency as well as improvement of cognition in children with rolandic
      epilepsy. We conclude, that treatment with anti-epileptic drugs could be
      justified, if treatment reduces seizures, prevents the evolution to atypical
      forms, or diminishes the negative cognitive consequences associated with the
      disease. Levetiracetam and sulthiame are the recommended treatments according to
      the existing evidence, which is still insufficient. A larger randomized
      controlled trial is warranted.

PMID- 29208198
TI  - [Idiopathic oedema].
AB  - Idiopathic oedema is a non-inflammatory interstitial oedema seen in fertile
      women. A hallmark is a daily increase in weight > 1.4 kg from morning until
      evening due to fluid retention, which shows as facial puffiness in the morning
      and more often abdominal increase and swollen lower extremities during the day.
      Patients may be disabled due to accompanying symptoms like headache, dizziness,
      fatigue, anxiety, and depression. The diagnosis is based on clinical features and
      exclusion of other causes of oedema. Non-pharmacological interventions and
      pharmacological therapies are reviewed.

PMID- 29208199
TI  - [Amputation of an arm due to infection with Vibrio vulnificus after beach
      holiday].
AB  - Infection with Vibrio vulnificus is a rare condition with approximately 11 cases
      reported in the Danish literature. It is characterized by soft tissue
      infection/wound, necrotizing fasciitis and septicaemia. In this case report we
      present a patient admitted with a rapid progression and sepsis consistent with V.
      vulnificus infection but with no informa-tion of water exposure. The initial
      treatment was surgery and sepsis management including broad-spectrum antibiotics.
      On day eight the patient's right arm was amputated. On day 16 the patient was
      discharged from the intensive care unit, and on day 32 the patient was
      transferred to a local hospital.

PMID- 29208200
TI  - [Primary septic arthritis is a rare, atypical manifestation of invasive
      meningococcal disease].
AB  - We present a case report of a 50-year-old man diagnosed with a primary septic
      arthritis with invasive Neisseria meningitidis serogroup W (MenW) clonal complex
      11 identified with culture in blood and synovial fluid. The patient recovered
      from rapidly instituted relevant antibiotics and synovectomy, but there may be a
      risk of fatal delayed diagnosis and treatment by an atypical manifestation of
      invasive meningococcal disease. Invasive MenW disease has been increasing in
      recent years and has been described with atypical presentations.

PMID- 29208201
TI  - [Osteochondritis dissecans].
AB  - Osteochondritis dissecans (OCD) has been known for more than 100 years. Several
      reasons have been suggested as the major cause for developing OCD:
      trauma/microtrauma, ischaemic or genetic reasons. OCD is primarily located in the
      knee. In adolescent patients with knee symptoms, X-ray of the affected knee and
      often a subsequent MRI scan is indicated. Depending on the findings, an
      arthroscopy can be performed. Conservative treatment can be quiet regime or
      bracing. Operative treatment can be transchondral/retrograde drilling for the in
      situ lesion or fixation of the unstable lesion.

PMID- 29208202
TI  - [Deformities of the finger joints].
AB  - Extension of the fingers is a complex act. Boutonniere deformity is defined by
      flexion at the proximal inter-phalangeal (PIP) joint and hyperextension at the
      distal interphalangeal (DIP) joint due to disruption of the central slip of the
      extensor tendon. Swan neck deformity is defined by hyperextension at the PIP
      joint and flexion at the DIP joint, and the pathology is divided into intrinsic,
      extrinsic, and articular. The deformities are a result of imbalance of the
      tendons and ligaments in the fingers. Treatment is depending on the underlying
      cause and includes surgery and non-operative treatment. Functional gain and risk
      must be realistically assessed.

PMID- 29208203
TI  - Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers on renal function in patients with chronic renal
      failure: A meta-analysis of randomized controlled trials?.
AB  - OBJECTIVE: <italic>Rheum officinale</italic> is a traditional medicinal herb used
      widely in China to treat chronic renal failure, but the proof of evidence-based
      medicine is poor. This meta-analysis aims to assess the benefits of angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs)
      supplemented with <italic>Rheum officinale</italic> for delaying the progression
      of chronic renal failure. MATERIALS AND METHODS: The MEDLINE, EMBASE, Cochrane
      Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP
      databases were searched to identify studies published before September 2016 that
      investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum
      (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and
      blood urea nitrogen (BUN) levels in chronic renal failure patients. Review
      Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects
      models were used to analyze the data. RESULTS: The meta-analysis included nine
      clinical trials. Comparisons of patients before and after treatment with ACEI/ARB
      plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted
      in significantly greater reductions in SCr (short-term: weighted mean difference
      (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71,
      95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long
      term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. CONCLUSION: In
      patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB
      significantly lowered both SCr and BUN, particularly after long-term
      administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the
      treatment of patients with impaired renal function.?.

PMID- 29208204
TI  - Durable renal response after combination of bortezomib, corticosteroids,
      rituximab, and plasmapheresis for late antibody-mediated renal transplant
      rejection?.
AB  - : Late occurrence of antibody-mediated rejection (AMR), defined as occurring 6
      months after transplantation, is associated with poor renal allograft survival,
      compared to early acute AMR and acute cellular rejection. The proteasome
      inhibitor bortezomib has multiple immunomodulatory effects on plasma cells, the
      source of donor-specific HLA antibodies which mediate AMR. MATERIALS AND METHODS:
      Consecutive patients who presented with biopsy-proven AMR and donor-specific anti
      HLA antibodies (DSA) at a single institution between July 2011 and February 2015
      were included. They received rituximab 375 mg/m<sup>2</sup> on day 1, bortezomib
      1.3 mg/m<sup>2</sup> and methylprednisolone on days 1, 4, 8, 11, and
      plasmapheresis on days -1, 4, 8, 11, 14, 15, 17, with herpes zoster prophylaxis.
      The primary outcome was graft survival independent of dialysis. Patients were
      prospectively assessed with serial monitoring of renal function and proteinuria,
      and neuropathy symptoms. Toxicity determination was made by medical record review
      for hospitalizations within 3 months of therapy, or documentation of
      opportunistic infection. RESULTS: Eleven patients were treated for late AMR
      (diagnosed at a median of 38 months post renal transplant) with this bortezomib
      based protocol; 2 patients underwent the regimen twice. Of the 11 patients, 9
      have functioning allografts (82% graft survival) with a median creatinine of 2.1
      mg/dL (range 1.1 - 3.4 mg/dL), at a median follow-up of 50 months after AMR
      therapy (range 24 - 63 months). One patient was re-transplanted at 4 years post
      AMR treatment with no AMR recurrence to date at 2-years' follow-up, and a second
      patient re-initiated dialysis at 2 years post AMR treatment. Patient survival is
      91% (10/11): 1 patient relocated out of state and was reported to have died from
      complications of hypertensive encephalopathy. The majority of patients (7/11) had
      several class I and class II DSA specificities; of these, 4 patients had negative
      class I DSA but persistent class II DSAs at 2 - 3 months post therapy. Only 1
      patient who was positive for class II DSAs alone (DR53 and DQ2) converted to
      negative DSA, although DSA testing was delayed to 2 years' follow-up. Two
      patients were hospitalized within 1 month of the protocol, 1 for ileus and 1 for
      urinary tract infection and ruptured ovarian cyst. One other patient had herpes
      zoster. CONCLUSION: Renal allograft survival was 82% at 4 years after bortezomib
      based therapy for late onset AMR; toxicity profile of this regimen was
      acceptable. Eradication of DSAs may not be necessary for meaningful and durable
      renal response.?.

PMID- 29208205
TI  - Dense deposit disease associated with multiple myeloma?.
AB  - Dense deposit disease (DDD) is a very rare pathological finding associated with
      activation of the final complement pathway. DDD has been rarely found in
      association with multiple myeloma (MM). Here we report a patient with MM
      presenting with renal failure, anemia, and bone pain. The renal biopsy showed
      DDD. The patient received anti-myeloma treatment and responded well. The case is
      discussed and literature reviewed.?.

PMID- 29208206
TI  - Prospective study of NSAIDs prescribing in Saudi Arabia: Cardiovascular and
      gastrointestinal risk in patients with diabetes mellitus?.
AB  - OBJECTIVES: The purpose of this study was to investigate the patterns of
      nonsteroidal anti-inflammatory drug (NSAID) prescriptions in diabetes mellitus
      (DM) patients and to evaluate their suitability based on patient
      gastrointestinal/cardiovascular (GI/CV) risk profiles. MATERIALS AND METHODS: We
      retrospectively identified patients with DM, who were seen at a primary care
      facility from March 1 to 31, 2016. GI risk factors, CV histories, and current
      medications were recorded. Data were evaluated for appropriateness of NSAID
      prescribing by using current understanding and accepted guidelines. RESULTS: A
      total of 443 evaluable patients were reviewed. NSAIDs were prescribed in 171
      patients (38.5%). Ibuprofen (23.5%) was the most frequently prescribed drug,
      followed by celecoxib (20%) and naproxen (14.1%). Of 171 patients, 76 (44.4%) had
      a previous history of CV events, while 52 patients without CV history had a
      moderate to very high 10-year risk of heart disease. Markedly fewer patients with
      CV history (19.1%) than patients without CV history were prescribed naproxen.
      Patients at high GI risk (22.9%) were prescribed traditional NSAIDs without a
      gastroprotective agent. Overall, 22.9% of patients at high GI risk and 65.8% at
      high CV risk were prescribed NSAIDs that were not in accordance with current
      guidelines or recommendations of regulatory agencies. CONCLUSION: Inappropriate
      prescribing of NSAIDs was found in more than half of the studied DM patients who
      were at risk for significant GI and CV adverse events. Assessment of GI and CV
      risks in DM patients is crucial to tailor NSAID selection and optimize patient
      outcomes.?.

PMID- 29208207
TI  - Corrigendum to "Chlorin E6 phototoxicity in L. major and L. braziliensis
      promastigotes-In vitro study" [Photodiagn. Photodyn. Ther. 15 (September) (2016)
      19-24].

PMID- 29208208
TI  - Corrigendum to "Photoinactivation of single and mixed biofilms of Candida
      albicans and non-albicans Candida species using Photodithazine(r)"[Photodiagn.
      Photodyn. Ther. 17C (2017) 194-199].

PMID- 29208209
TI  - Imepitoin withdrawal in dogs with idiopathic epilepsy well-controlled with
      imepitoin and phenobarbital and/or potassium bromide does not increase seizure
      frequency.
AB  - Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average
      monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum
      dose of imepitoin. The importance of continued administration of imepitoin in
      these dogs is currently unknown. The goal of this study was to assess whether
      imepitoin withdrawal would destabilize epileptic seizure control. In this
      prospective clinical trial epileptic seizure control was evaluated by comparing
      the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy
      receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr
      (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3-6 months
      (pre-withdrawal period), with a follow-up period of 9-12 months after withdrawal
      of imepitoin (post-withdrawal period). Adverse effects were also recorded before
      and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as
      follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month,
      then once daily for 1 month. Withdrawal of imepitoin did not increase monthly
      seizure frequency (P=0.9). Moreover, all owners reported improvement in the
      adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin
      withdrawal in epileptic dogs that were well-controlled with imepitoin and
      phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly
      decreased antiepileptic treatment-related adverse effects. However, a worsening
      of seizure frequency could occur in individual cases.

PMID- 29208210
TI  - Evaluation of the delta neutrophil index from an automated blood cell analyser in
      septic dogs.
AB  - Immature granulocytes (IG) are a marker of severe inflammatory states in human
      beings and animals, and have been linked to a diagnosis of sepsis and poor
      prognosis. The delta neutrophil index (DNI), automatically calculated by a
      haematological analyser, provides an estimate of circulating IG. In particular,
      an increased DNI value has been associated with the severity of sepsis, and
      mortality, in critically ill human beings. The aims of this study were to
      determine the DNI reference interval (RI) in healthy dogs, and to evaluate its
      diagnostic and prognostic significance in dogs with sepsis. A total of 118 dogs
      with sepsis undergoing a complete blood cell count (CBC) at the time of hospital
      admission were included retrospectively. Dogs with sepsis were compared to 20
      dogs with primary immune-mediated haemolytic anaemia (IMHA) and 99 healthy
      controls. The DNI RI was set from 0 to 9.2%. The DNI was significantly higher in
      dogs with sepsis compared to dogs with IMHA and healthy dogs (P<0.001), and
      significantly higher in dogs with septic shock compared to septic dogs without
      circulatory failure (P<0.03). No differences were detected between survivors
      (78/118) and non-survivors (40/118). Septic dogs with a DNI above the RI had
      significantly higher frequencies of IG and toxic neutrophil changes on manual
      blood smear evaluation (P=0.03 and P<0.001, respectively). The DNI had a fair
      performance in identifying dogs with sepsis in this population and predicted
      septic shock. Larger prospective studies are needed to validate DNI measurement
      in dogs and to test its clinical utility.

PMID- 29208211
TI  - Plasma firocoxib concentrations after intra-articular injection of autologous
      conditioned serum prepared from firocoxib positive horses.
AB  - Orthobiologics such as autologous conditioned serum (ACS) are often used to treat
      joint disease in horses. Because ACS is generated from the horse's own blood, any
      medication administered at the time of preparation would likely be present in
      stored ACS, which could lead to an inadvertent positive drug test following intra
      articular (IA) injection. The main objective of this study was to determine if
      ACS prepared from firocoxib positive horses could result in detectable plasma
      concentrations of the drug following IA injection. Firocoxib was administered to
      six horses at 0.1mg/kg PO twice at a 24h interval. Blood was obtained at 4h
      following the second dose and transferred to a separate syringe (Arthrex IRAP II)
      for ACS preparation. Plasma and ACS concentrations of firocoxib were analysed by
      liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). When
      horses were confirmed firocoxib negative, 7.5mL of ACS was injected into both
      tarsocrural joints. Blood samples were collected at 0, 4, 8, 12, 24, and 48h, and
      firocoxib concentration was measured. Mean (+/-standard error of the mean, SEM)
      plasma concentration of firocoxib 4h following the second dose was 33.3+/
      4.72ng/mL. Mean (+/-SEM) firocoxib concentration in ACS was 35.4+/-4.47ng/mL.
      Fourteen days following the second and last dose of firocoxib, mean plasma
      concentration was below the lower limit of detection (LOD=1ng/mL) in all horses.
      Following IA injection of ACS, plasma concentrations of firocoxib remained below
      LOD at all times in all horses. ACS generated from horses with therapeutic plasma
      concentrations of firocoxib did not contain sufficient firocoxib to lead to a
      positive plasma drug test following IA administration.

PMID- 29208212
TI  - Incidence and risk factors for hypoadrenocorticism in dogs treated with
      trilostane.
AB  - The aim of this study was to describe the incidence and permanence of
      hypoadrenocorticism associated with trilostane treatment and to assess potential
      risk factors for hypoadrenocorticism. A retrospective cohort study was conducted
      using case records for 156 dogs treated with trilostane after a diagnosis of
      hyperadrenocorticism. Occurrences of hypoadrenocorticism were categorised as
      either transient or permanent. After initiation of treatment with trilostane, the
      estimated cumulative incidence of hypoadrenocorticism was 15% by 2 years and 26%
      by 4.3 years, respectively. Occurrences of hypoadrenocorticism were transient in
      14/19 (74%) affected study dogs. The risk of hypoadrenocorticism was not
      significantly associated with trilostane dose rate and other potential risk
      factors assessed were not significantly associated with subhazard of
      hypoadrenocorticism, but effect estimates for most were imprecise. In conclusion,
      approximately 15% of dogs being treated with trilostane developed
      hypoadrenocorticism within the first 2 years of treatment and about one quarter
      became affected by 4 years. However, first occurrences of hypoadrenocorticism
      were mostly transient. Over the range of dose rates studied, each 1mg/kg/day
      increase in trilostane dose rate resulted in, at most, only a small increase in
      the risk of developing hypoadrenocorticism.

PMID- 29208213
TI  - Evaluation of ex vivo restoration of carious equine maxillary cheek teeth
      infundibulae following debridement with dental drills and Hedstrom files.
AB  - An ex-vivo study was performed on vertically mounted equine maxillary cheek teeth
      that had caries of 30 infundibulae, using high and low speed contra-angle dental
      drills and Hedstrom files to debride infundibular food debris and carious dental
      tissues. This technique effectively debrided 27/30 infundibulae with a mean depth
      of 19mm (range 9.4-34.3mm) as assessed by computed tomographic (CT) imaging. The
      debrided infundibulae were treated with sodium hypochlorite, EDTA and a bonding
      agent, and then then filled in layers with endodontic restoration materials.
      Further CT imaging and direct examination of sectioned restored teeth showed 6/30
      infundibulae, including three that were incompletely debrided, to have defects
      between the restoration and the infundibular wall/apex. Twenty-one of the
      remaining 24 infundibulae contained air bubbles, largely within restorations. It
      is concluded that the use of drills and Hedstrom files is effective in debriding
      carious infundibulae but improved techniques and materials are required to more
      effectively fill infundibulae with restorative material.

PMID- 29208214
TI  - Proof of concept of a new autologous skin substitute for the treatment of deep
      wounds in dogs.
AB  - Autologous skin grafts are effective for the repair of large skin wounds, but the
      availability of large amounts of skin is often limited. Through bioengineering,
      several autologous skin substitutes have been developed for use in human clinical
      practice. However, few skin substitutes are available for use in animals. The aim
      of this study was to develop and assess an engineered autologous skin substitute
      for the treatment of deep wounds in veterinary medicine. Canine keratinocytes and
      fibroblasts were isolated after double enzyme digestion from 8mm punch biopsies
      from four healthy Beagle dogs. Skin substitutes were constructed on a fibrin
      based matrix and grafting capacity was assessed by xenografting in six athymic
      mice. Bioengineered autologous skin was assessed clinically in two dogs with
      large deep skin wounds. The canine skin construct was ready for use within 12
      14days after the initial biopsy specimens were obtained. Grafting capacity in
      this model was confirmed by successful grafting of the construct in athymic mice.
      In both dogs, grafts were established and permanent epithelialisation occurred.
      Histological studies confirmed successful grafting. This full thickness skin
      substitute developed for the management of large skin defects in dogs appears to
      be a safe and useful tool for clinical veterinary practice. Further studies are
      needed to validate its efficacy for the treatment of deep wounds.

PMID- 29208215
TI  - Plasma potassium concentrations in neonatal diarrhoeic calves are correlated with
      serum aldosterone concentrations but not with insulin concentrations.
AB  - Hyperkalaemia is a clinically relevant electrolyte imbalance in neonatal
      diarrhoeic calves which was previously associated with severe dehydration and
      acidaemia. The present study assessed the association of plasma potassium (cK)
      with serum aldosterone and insulin concentrations, since these hormones are
      involved in the regulation of potassium homeostasis. Serum aldosterone (rs=0.62),
      but not insulin concentrations (rs=0.22) were closely correlated to cK in 123
      hospitalised neonatal diarrhoeic calves. Median values for serum aldosterone
      concentrations in 38 hyperkalaemic calves (cK>5.8mmol/L) were 3.2 and 15.3 times
      higher (P<0.001) than in 85 non-hyperkalaemic diarrhoeic calves and nine healthy
      control calves, respectively. Aldosterone, but not insulin secretion, appears to
      be highly stimulated in dehydrated diarrhoeic calves with hyperkalaemia, but
      hypovolaemia and a concomitant decrease in renal perfusion and urinary flow rate
      are likely to limit the efficacy of aldosterone-induced control mechanisms in
      these animals.

PMID- 29208216
TI  - Clinical veterinary proteomics: Techniques and approaches to decipher the animal
      plasma proteome.
AB  - Over the last two decades, technological advancements in the field of proteomics
      have advanced our understanding of the complex biological systems of living
      organisms. Techniques based on mass spectrometry (MS) have emerged as powerful
      tools to contextualise existing genomic information and to create quantitative
      protein profiles from plasma, tissues or cell lines of various species. Proteomic
      approaches have been used increasingly in veterinary science to investigate
      biological processes responsible for growth, reproduction and pathological
      events. However, the adoption of proteomic approaches by veterinary investigators
      lags behind that of researchers in the human medical field. Furthermore, in
      contrast to human proteomics studies, interpretation of veterinary proteomic data
      is difficult due to the limited protein databases available for many animal
      species. This review article examines the current use of advanced proteomics
      techniques for evaluation of animal health and welfare and covers the current
      status of clinical veterinary proteomics research, including successful protein
      identification and data interpretation studies. It includes a description of an
      emerging tool, sequential window acquisition of all theoretical fragment ion mass
      spectra (SWATH-MS), available on selected mass spectrometry instruments. This
      newly developed data acquisition technique combines advantages of discovery and
      targeted proteomics approaches, and thus has the potential to advance the
      veterinary proteomics field by enhancing identification and reproducibility of
      proteomics data.

PMID- 29208217
TI  - Humidity sensing in insects-from ecology to neural processing.
AB  - Humidity is an omnipresent climatic factor that influences the fitness,
      reproductive behavior and geographic distribution of animals. Insects in
      particular use humidity cues to navigate the environment. Although the sensory
      neurons of this elusive sense were first described more than fifty years ago, the
      transduction mechanism of humidity sensing (hygrosensation) remains unknown.
      Recent work has uncovered some of the key molecules involved, opening up for
      novel approaches to study hygrosensory transduction. In this review, I will
      discuss this progress made toward understanding hygrosensation in insects.

PMID- 29208218
TI  - Drosophila as a holistic model for insect pheromone signaling and processing.
AB  - In recent years, research into the chemical ecology of the vinegar fly,
      Drosophila melanogaster, has yielded a wealth of information on the neural
      substrates that detect and process pheromones and control behavior. The studies
      reveal at the cellular and molecular level how behavioral responses to pheromones
      are initiated and modulated by social, environmental, and physiological factors.
      By taking into account both the complexity of the chemical world and the
      intricacies of the animal's physiological state, the emerging holistic
      perspective provides insight not only into chemical communication but more
      generally, how organisms balance internal and external signals when making
      behavioral decisions.

PMID- 29208219
TI  - Neuronal modulation of D. melanogaster sexual behaviour.
AB  - Drosophila melanogaster sexual behaviour relies on well-studied genetically
      determined neuronal circuits. At the same time, it can be flexible and is
      modulated by multiple external and internal factors. This review focuses on how
      physiological state, behavioural context and social experience impact sexual
      circuits in the two sexes. We discuss how females tune receptivity and other
      behaviours depending on mating status and how males adjust courtship intensity
      based on sexual satiety, age and the conflicting drive for aggression. Neuronal
      mechanisms for behavioural modulation include changes in sensory and central
      processing. Activity of modulatory neurons can enhance, suppress or reverse the
      behavioural response to sensory cues. In summary, fly sexual behaviour is an
      excellent model to study mechanisms of neuromodulation of complex innate
      behaviour on the circuit level.

PMID- 29208220
TI  - Regulation of pheromone biosynthesis in moths.
AB  - Female moths release sex pheromones for attracting males from a distance. Most
      moths are nocturnal so there is a periodicity to the release of sex pheromone.
      The temporal release of sex pheromone in most moths is regulated by calling
      behavior and by the biosynthesis of sex pheromone. In most moths, biosynthesis
      occurs in the pheromone gland and is controlled by the neuropeptide PBAN
      (pheromone biosynthesis activating neuropeptide). PBAN is produced in the
      subesophageal ganglion and released into circulation where it travels to the
      pheromone gland to activate pheromone biosynthesis. The G-protein coupled
      receptor that binds PBAN has been identified as well as aspects of signal
      transduction to activate the biosynthetic pathway. This review will highlight
      recent advances in the study of regulation of pheromone biosynthesis in moths.

PMID- 29208221
TI  - Evolutionary origin of insect pheromones.
AB  - Communication via chemical signals, that is, pheromones, is of pivotal importance
      for most insects. According to current evolutionary theory, insect pheromones
      originated either from extant precursor compounds being selected for information
      transfer or by the pheromone components exploiting a pre-existing sensory bias in
      the receiver. Here, we review the available experimental evidence for both
      hypotheses. Existing data indicate that most insect pheromones evolved from
      precursor compounds that were emitted as metabolic by-products or that previously
      had other non-communicative functions. Many studies have investigated cuticular
      hydrocarbons that have evolved a communicative function, although examples of
      pheromones exist that have arisen from defensive secretions, hormones or dietary
      compounds. We summarize and discuss the selective pressures shaping the pheromone
      during signal evolution.

PMID- 29208222
TI  - Using virtual reality to study visual performances of honeybees.
AB  - Virtual reality (VR) offers an appealing experimental framework for studying
      visual performances of insects under highly controlled conditions. In the case of
      the honeybee Apis mellifera, this possibility may fill the gap between
      behavioural analyses in free-flight and cellular analyses in the laboratory.
      Using automated, computer-controlled systems, it is possible to generate virtual
      stimuli or even entire environments that can be modified to test hypotheses on
      bee visual behaviour. The bee itself can remain tethered in place, making it
      possible to record neural activity while the bees is performing behavioural
      tasks. Recent studies have examined visual navigation and attentional processes
      in VR on flying or walking tethered bees, but experimental paradigms for
      examining visual learning and memory are only just emerging. Behavioural
      performances of bees under current experimental conditions are often lower in VR
      than in natural environments, but further improvements on current experimental
      protocols seem possible. Here we discuss current developments and conclude that
      it is essential to tailor the specifications of the VR simulation to the visual
      processing of honeybees to improve the success of this research endeavour.

PMID- 29208223
TI  - Neuronal and molecular mechanisms of sleep homeostasis.
AB  - Sleep is necessary for survival, and prolonged waking causes a homeostatic
      increase in the need for recovery sleep. Homeostasis is a core component of sleep
      regulation and has been tightly conserved across evolution from invertebrates to
      man. Homeostatic sleep regulation was first identified among insects in
      cockroaches several decades ago, but the characterization of sleep rebound in
      Drosophila melanogaster opened the use of insect model species to understand
      homeostatic functions and regulation of sleep. This review describes circuits in
      two neuropil structures, the central complex and mushroom bodies, that influence
      sleep homeostasis and neuromodulatory systems that influence the accrual of
      homeostatic sleep need.

PMID- 29208225
TI  - Pheromone biosynthesis in bark beetles.
AB  - Pine bark beetles rely on aggregation pheromones to coordinate mass attacks and
      thus reproduce in host trees. The structural similarity between many pheromone
      components and those of defensive tree resin led to early suggestions that
      pheromone components are metabolic derivatives of ingested precursors. This model
      has given way to our current understanding that most pheromone components are
      synthesized de novo. Their synthesis involves enzymes that modify products from
      endogenous metabolic pathways; some of these enzymes have been identified and
      characterized. Pheromone production is regulated in a complex way involving
      multiple signals, including JH III. This brief review summarizes progress in our
      understanding of this highly specialized metabolic process.

PMID- 29208224
TI  - Unraveling the neural basis of insect navigation.
AB  - One of the defining features of animals is their ability to navigate their
      environment. Using behavioral experiments this topic has been under intense
      investigation for nearly a century. In insects, this work has largely focused on
      the remarkable homing abilities of ants and bees. More recently, the neural basis
      of navigation shifted into the focus of attention. Starting with revealing the
      neurons that process the sensory signals used for navigation, in particular
      polarized skylight, migratory locusts became the key species for delineating
      navigation-relevant regions of the insect brain. Over the last years, this work
      was used as a basis for research in the fruit fly Drosophila and extraordinary
      progress has been made in illuminating the neural underpinnings of navigational
      processes. With increasingly detailed understanding of navigation circuits, we
      can begin to ask whether there is a fundamentally shared concept underlying all
      navigation behavior across insects. This review highlights recent advances and
      puts them into the context of the behavioral work on ants and bees, as well as
      the circuits involved in polarized-light processing. A region of the insect brain
      called the central complex emerges as the common substrate for guiding navigation
      and its highly organized neuroarchitecture provides a framework for future
      investigations potentially suited to explain all insect navigation behavior at
      the level of identified neurons.

PMID- 29208226
TI  - Image statistics and their processing in insect vision.
AB  - Natural scenes may appear random, but are not only constrained in space and time,
      but also show strong spatial and temporal correlations. Spatial constraints and
      correlations can be described by quantifying image statistics, which include
      intuitive measures such as contrast, color and luminance, but also parameters
      that need some type of transformation of the image. In this review we will
      discuss some common tools used to quantify spatial and temporal parameters of
      naturalistic visual input, and how these tools have been used to inform us about
      visual processing in insects. In particular, we will review findings that would
      not have been possible using conventional, experimenter defined stimuli.

PMID- 29208228
TI  - Pheromones-based sexual selection in a rapidly changing world.
AB  - Insects utilise chemical cues for a range of different purposes and the
      complexity and degree of specificity of these signals is arguably unparalleled in
      the animal kingdom. Chemical signals are particularly important for insect
      reproduction and the selective pressures driving their evolution and maintenance
      have been the subject of previous reviews. However, the world in which chemical
      cues evolved and are maintained is changing at an unprecedented rate. How (or
      indeed whether) chemical signals used in sexual selection will respond is largely
      unknown. Here, we explore how recent increases in urbanisation and associated
      anthropogenic impacts may affect how chemical signals are produced and perceived.
      We focus on four anthropomorphic influences which have the potential to interact
      with pheromone-mediated sexual selection processes; climatic temperature shifts,
      exposure to chemical pollutants, the presence of artificial light at night and
      nutrient availability. Our aim is to provide a broad overview of key areas where
      the rapidly changing environment of the future might specifically affect
      pheromones utilised in sexual selection.

PMID- 29208227
TI  - Retinal perception and ecological significance of color vision in insects.
AB  - Color vision relies on the ability to discriminate different wavelengths and is
      often improved in insects that inhabit well-lit, spectrally rich environments.
      Although the Opsin proteins themselves are sensitive to specific wavelength
      ranges, other factors can alter and further restrict the sensitivity of
      photoreceptors to allow for finer color discrimination and thereby more informed
      decisions while interacting with the environment. The ability to discriminate
      colors differs between insects that exhibit different life styles, between female
      and male eyes of the same species, and between regions of the same eye, depending
      on the requirements of intraspecific communication and ecological demands.

PMID- 29208229
TI  - Pheromones involved in insect parental care and family life.
AB  - Effective parental care requires recognition and communication processes. Whereas
      chemical communication has been studied intensively in eusocial organisms, in
      which the workers (siblings) predominantly provide brood care, insect groups in
      which parents engage in care have been largely neglected. However, the study of
      communication in insect families might complement and enhance our understanding
      not only of the evolution of signaling process involved in social insects, but
      also of those involved in vertebrate families. In this review, we synthesize the
      existing information about the pheromones and chemical cues that regulate and
      affect insect parental care and family life. We will present research dealing
      with pre-hatching as well as post-hatching parental care and cover interactions
      between parents and offspring, between male and female parents, and among
      siblings.

PMID- 29208230
TI  - Learning from connectomics on the fly.
AB  - Parallels between invertebrates and vertebrates in nervous system development,
      organisation and circuits are powerful reasons to use insects to study the
      mechanistic basis of behaviour. The last few years have seen the generation in
      Drosophila melanogaster of very large light microscopy data sets, genetic driver
      lines and tools to report or manipulate neural activity. These resources in
      conjunction with computational tools are enabling large scale characterisation of
      neuronal types and their functional properties. These are complemented by 3D
      electron microscopy, providing synaptic resolution data. A whole brain connectome
      of the fly larva is approaching completion based on manual reconstruction of
      electron-microscopy data. An adult whole brain dataset is already publicly
      available and focussed reconstruction is under way, but its 40* greater volume
      would require ~500-5000 person-years of manual labour. Nevertheless rapid
      technical improvements in imaging and especially automated segmentation will
      likely deliver a complete adult connectome in the next 5 years. To enhance our
      understanding of the circuit basis of behaviour, light and electron microscopy
      outputs must be integrated with functional and physiological information into
      comprehensive databases. We review presently available data, tools and
      opportunities in Drosophila. We then consider the limits and potential of future
      progress and how this may impact neuroscience in rich model systems provided by
      larger insects and vertebrates.

PMID- 29208231
TI  - Editorial overview: Recent advances in insect neuroethology: from sensory
      processing to circuits controlling internal states.

PMID- 29208232
TI  - Editorial overview: Insect pheromones: making sense of a rapidly diversifying
      field of study.

PMID- 29208233
TI  - From testing to diagnostic strategies and dia-prognostic research.

PMID- 29208235
TI  - Modelling the effect of intervillous flow on solute transfer based on 3D imaging
      of the human placental microstructure.
AB  - INTRODUCTION: A healthy pregnancy depends on placental transfer from mother to
      fetus. Placental transfer takes place at the micro scale across the placental
      villi. Solutes from the maternal blood are taken up by placental villi and enter
      the fetal capillaries. This study investigated the effect of maternal blood flow
      on solute uptake at the micro scale. METHODS: A 3D image based modelling approach
      of the placental microstructures was undertaken. Solute transport in the
      intervillous space was modelled explicitly and solute uptake with respect to
      different maternal blood flow rates was estimated. Fetal capillary flow was not
      modelled and treated as a perfect sink. RESULTS: For a freely diffusing small
      solute, the flow of maternal blood through the intervillous space was found to be
      limiting the transfer. Ignoring the effects of maternal flow resulted in a 2.4 +/
      0.4 fold over-prediction of transfer by simple diffusion, in absence of binding.
      Villous morphology affected the efficiency of solute transfer due to
      concentration depleted zones. Interestingly, less dense microvilli had lower
      surface area available for uptake which was compensated by increased flow due to
      their higher permeability. At super-physiological pressures, maternal flow was
      not limiting, however the efficiency of uptake decreased. CONCLUSIONS: This study
      suggests that the interplay between maternal flow and villous structure affects
      the efficiency of placental transfer but predicted that flow rate will be the
      major determinant of transfer.

PMID- 29208234
TI  - Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of
      extravillous trophoblast migration.
AB  - INTRODUCTION: Failure of trophoblast invasion and remodelling of maternal blood
      vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems,
      the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration
      therefore this study determined its effect on extravillous trophoblast (EVT)
      function. METHODS: A transwell migration system was used to assess the behaviour
      of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human
      trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and
      1,25(OH)2D3. QPCR and immunolocalisation were used to demonstrate EVT S1P
      receptor expression. RESULTS: EVTs express S1P receptors 1, 2 and 3. S1P
      inhibited EVT migration. This effect was abolished in the presence of the
      specific S1PR2 inhibitor, JTE-013 (p < 0.05 versus S1P alone) whereas treatment
      with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is
      regulated by vitamin D; here we found that treatment with 1,25(OH)2D3 for 48 or
      72 h reduces S1PR2 (4-fold; <0.05), but not R1 and R3, expression. Moreover, S1P
      did not inhibit the migration of cells exposed to 1,25(OH)2D3 (p < 0.05).
      DISCUSSION: This study demonstrates that although EVT express three S1P receptor
      isoforms, S1P predominantly signals through S1PR2/Galpha12/13 to activate Rho and
      thereby acts as potent inhibitor of EVT migration. Importantly, expression of
      S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data
      suggest that vitamin D deficiency, which is known to be associated with PE, may
      contribute to the impaired trophoblast migration that underlies this condition.

PMID- 29208236
TI  - Placental abnormalities differ between small for gestational age fetuses in
      dichorionic twin and singleton pregnancies.
AB  - OBJECTIVE: Twin fetuses grow slower during the third trimester compared with
      singletons. However, the extent to which the relative smallness of twins is the
      result of placenta-mediated factors similar to those associated with fetal growth
      restriction in singletons remains unclear. Our aim was to address this question
      by comparing placental findings between small for gestational age (SGA) twins and
      SGA singletons. METHODS: Retrospective cohort study of all SGA non-anomalous
      newborns from singleton and dichorionic twin pregnancies in a single tertiary
      referral center between 2002 and 2015. SGA was defined as birth weight <10th
      percentile for gestational age according to sex-specific national reference
      charts. Placental findings were compared between SGA twins and SGA singletons and
      were classified into lesions associated with maternal vascular malperfusion,
      fetal vascular malperfusion, placental hemorrhage and chronic villitis. RESULTS:
      A total of 532 SGA twins and 954 SGA singletons met the inclusion criteria. SGA
      twins had a higher mean placental weight (371 +/- 103 g vs. 319 +/- 107, p <
      0.001) and a lower fetal-placental ratio (6.0 +/- 2.5 vs. 6.7 +/- 3.2, p < 0.001)
      compared with SGA singletons. Compared with SGA singletons, SGA twins were less
      likely to have any placental pathology (aOR 0.37, 95%-CI 0.29-0.46), hypercoiled
      cord (aOR 0.45, 95%-CI 0.33-0.61), placental weight<10th% (aOR 0.13, 95%-CI 0.08
      0.20), maternal vascular malperfusion pathology (aOR 0.24, 95%-CI 0.18-0.30) and
      fetal vascular malperfusion pathology (aOR 0.62, 95%-CI 0.48-0.82). By contrast,
      SGA twins had higher odds of a marginal or velamentous cord insertion compared
      with SGA singletons (aOR 13.82, 95%-CI 10.44-18.30). Similar significant
      associations were observed in subgroups of SGA fetuses with a birth weight below
      the 5th and 3rd percentile for gestational age. CONCLUSIONS: Our findings
      illustrate that the mechanisms underlying reduced fetal growth in dichorionic
      twins differ from those involved in singletons, and may provide support to the
      hypothesis that smallness in dichorionic twins may be more benign than in
      singletons.

PMID- 29208237
TI  - Imaging the human placental microcirculation with micro-focus computed
      tomography: Optimisation of tissue preparation and image acquisition.
AB  - Micro-CT provides 3D volume imaging with spatial resolution at the micrometre
      scale. We investigated the optimal human placenta tissue preparation (contrast
      agent, perfusion pressure, perfusion location and perfusion vessel) and imaging
      (energy, target material, exposure time and frames) parameters. Microfil (Flow
      Tech, Carver, MA) produced better fill than Barium sulphate (84.1%(+/
      11.5%)vs70.4%(+/-18.02%) p = 0.01). Perfusion via umbilical artery produced
      better fill than via chorionic vessels (83.8%(+/-17.7%)vs78.0%(+/-21.9%), p <
      0.05), or via umbilical vein (83.8%(+/-16.4%)vs69.8%(+/-20.3%), p < 0.01).
      Imaging at 50 keV with a molybdenum target produced the best contrast to noise
      ratio. We propose this method to enable quantification and comparison of the
      human fetoplacental vascular tree.

PMID- 29208238
TI  - Toll-like receptor-2 mediates local innate immune response against Trypanosoma
      cruzi in ex vivo infected human placental chorionic villi explants.
AB  - BACKGROUND: Congenital Chagas disease is caused by the protozoan parasite
      Trypanosoma cruzi that must cross the placental barrier during transmission. The
      trophoblast constitutes the first tissue in contact with the maternal-blood
      circulating parasite. Importantly, the congenital transmission rates are low,
      suggesting the presence of local placental defense mechanisms. On the other hand,
      the placenta is considered an immune regulatory organ since it acts as a
      modulator of fetal and maternal immune responses. We have previously proposed
      that local placental factors, such as the epithelial turnover of the trophoblast
      and the innate immune response initiated by Toll-like receptors (TLRs), might
      prevent parasite infection and congenital transmission. Here, we studied in an ex
      vivo infected human placental chorionic villi explant HPCVE model, the
      relationship between TLR-2 activation in response to T. cruzi trypomastigotes,
      the secreted profile of cytokines, the integrity of the placental barrier and the
      expression of trophoblast turnover markers. RESULTS: TLR-2 inhibition increases
      the parasite induced histopathological damage, prevents secretion of IL-6 and IL
      10, decreases expression of PCNA (proliferation marker) and of beta-hCG
      (differentiation marker) while increasing caspase 3 activity (cell death marker).
      CONCLUSION: Our results suggest that TLR-2 is not only involved in the local
      secretion of cytokines but also regulates, at least partially, the trophoblast
      turnover.

PMID- 29208239
TI  - Syncytial nuclei accumulate at the villous surface in IUGR while proliferation is
      unchanged.
AB  - INTRODUCTION: Placental syncytiotrophoblast is responsible for feto-maternal
      nutrient exchange during pregnancy. It is assumed that in IUGR, placental
      dysfunction is crucially bound to compromised stability and function of
      syncytiotrophoblast, the latter being related to altered proliferation of villous
      trophoblast. Cell cycle data obtained on conventional thin sections has produced
      inconsistent results. In the present study we investigated cell cycle markers
      found in the villous trophoblast using a novel 3D histological quantification
      method. METHODS AND FINDINGS: We analyzed 40 placentas from IUGR pregnancies and
      42 placentas from clinically normal pregnancies by immunohistochemical detection
      of the cell cycle marker PCNA. Nuclei immuno-positive for PCNA were quantified
      using 3D microscopy, and the results were compared to corresponding results
      obtained on conventional thin histological sections. These data did not show any
      evidence of altered trophoblast proliferation in IUGR, while the density of post
      proliferative (i.e. PCNA-negative) trophoblast nuclei was statistically
      significantly increased in IUGR. The latter could be revealed by 3D topological
      microscopy, but not by conventional histology of thin sections. DISCUSSION: The
      data of the present study indicate a previously unknown type of regulation of
      syncytial stability and function, independent of proliferation. We hypothesize
      that in IUGR, post-proliferative trophoblast nuclei accumulate at the villous
      surface of peripheral villous branches. This could possibly reflect the presence
      of an unknown mechanism controlling syncytial function and stability by
      modulation of syncytial passage time rather than by modulation of proliferative
      supply.

PMID- 29208240
TI  - Redness discordance in monochorionic twin placentas: Correlation with clinical
      and placental findings.
AB  - INTRODUCTION/OBJECTIVES: Recent studies suggest redness (color) discordance of
      the placental basal plate may be a marker for twin anemia-polycythemia sequence
      (TAPS), a recently described complication of diamniotic-monochorionic twinning
      characterized by marked intertwin hemoglobin (Hb) discordance in the absence of
      oligohydramnios-polyhydramnios. In this study, we determined the clinicoplacental
      and choriovascular correlates of basal plate color discordance in monochorionic
      twin placentas, and assessed its value as postnatal indicator of TAPS. METHODS:
      We performed a clinicoplacental analysis of 100 consecutive non-TTTS diamniotic
      monochorionic twin placentas with available photographic documentation of the
      basal plate. Basal plate redness was quantified by computer-assisted analysis of
      digital images and expressed as intertwin color difference ratio (CDR). RESULTS:
      The CDR ranged between 1.00 and 3.58 (median CDR: 1.14; 90th %ile: 1.98).
      Compared to twins with low CDR (N = 90), twins with high CDR (>=2.0; N = 10) had
      significantly higher hemoglobin difference (11.25 g/dL versus 2.55 g/dL) and
      significantly fewer and smaller artery-to-artery (AA) and artery-to-vein (AV)
      anastomoses. Apgar scores and birth weights were equivalent in both groups. Among
      the 10 twin sets with high CDR, six (60%) qualified as TAPS, as defined by
      intertwin Hb difference >8 g/dL and absent or very small AA and AV anastomoses.
      Conversely, 6 of 8 (75%) twin sets with TAPS had a CDR >= 2.0. CONCLUSION:
      Intertwin CDR correlates with intertwin hemoglobin difference and chorionic
      angioarchitecture. A CDR value >= 2.0 (the 90%ile value for CDR derived from the
      present cohort) has high specificity (96%), but relatively low positive
      predictive value (60%) as indicator of TAPS, as currently defined.

PMID- 29208241
TI  - Increased trophoblast inclusions in placentas from prematurely born infants: A
      potential marker of risk for preterm neurodevelopmental outcomes.
AB  - Trophoblast inclusions (TIs) are placental abnormalities of the trophoblast
      bilayer. Present in 2-8% of full-term placentas, they are associated with poor
      neurodevelopment, including autism. Although previously unstudied, examination of
      chorionic villi from 108 preterm births revealed a ~4 fold increase in the
      frequency of TIs (30.5%). Frequency of TIs was inversely related to gestational
      age (GA); 43% of placentas <30 weeks and 20% of placentas >=32 weeks had TIs
      (chi2 = 4.41, p = 0.036). This increased prevalence in preterm infants suggests
      that TIs may indicate adverse intrauterine processes or undetected genetic
      abnormalities and could identify infants at risk for poor neurodevelopment.

PMID- 29208242
TI  - DNA methylation of amino acid transporter genes in the human placenta.
AB  - INTRODUCTION: Placental transfer of amino acids via amino acid transporters is
      essential for fetal growth. Little is known about the epigenetic regulation of
      amino acid transporters in placenta. This study investigates the DNA methylation
      status of amino acid transporters and their expression across gestation in human
      placenta. METHODS: BeWo cells were treated with 5-aza-2'-deoxycytidine to inhibit
      methylation and assess the effects on amino acid transporter gene expression. The
      DNA methylation levels of amino acid transporter genes in human placenta were
      determined across gestation using DNA methylation array data. Placental amino
      acid transporter gene expression across gestation was also analysed using data
      from publically available Gene Expression Omnibus data sets. The expression
      levels of these transporters at term were established using RNA sequencing data.
      RESULTS: Inhibition of DNA methylation in BeWo cells demonstrated that expression
      of specific amino acid transporters can be inversely associated with DNA
      methylation. Amino acid transporters expressed in term placenta generally showed
      low levels of promoter DNA methylation. Transporters with little or no expression
      in term placenta tended to be more highly methylated at gene promoter regions.
      The transporter genes SLC1A2, SLC1A3, SLC1A4, SLC7A5, SLC7A11 and SLC7A10 had
      significant changes in enhancer DNA methylation across gestation, as well as gene
      expression changes across gestation. CONCLUSION: This study implicates DNA
      methylation in the regulation of amino acid transporter gene expression. However,
      in human placenta, DNA methylation of these genes remains low across gestation
      and does not always play an obvious role in regulating gene expression, despite
      clear evidence for differential expression as gestation proceeds.

PMID- 29208243
TI  - Resveratrol mitigates trophoblast and endothelial dysfunction partly via
      activation of nuclear factor erythroid 2-related factor-2.
AB  - INTRODUCTION: Maternal endothelial dysfunction underlying preeclampsia arises
      from excessive placental release of anti-angiogenic factors, such as soluble fms
      like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and activin A.
      Resveratrol, an activator of the nuclear factor erythroid 2-related factor-2
      (Nrf2) transcription factor, mediates the gene expression of antioxidant and
      vasoprotective factors that may counter the endothelial damage imposed by these
      anti-angiogenic factors. The objective of this study was to assess whether
      resveratrol could reduce placental oxidative stress and production of anti
      angiogenic factors in vitro and/or improve in vitro markers of endothelial
      dysfunction via Nrf2 activation. METHOD: We used in vitro term placental explants
      to assess the effects of resveratrol on placental oxidative stress and production
      of sFlt1, sEng and activin A. Using human umbilical vein endothelial cells we
      investigated the effects of resveratrol on markers of in vitro endothelial
      dysfunction, including the expression of intercellular adhesion molecule 1
      (ICAM1), vascular cell adhesion molecule 1 (VCAM1), E-selectin and endothelin-1,
      and endothelial permeability. To confirm that resveratrol mediated its effects
      via Nrf2, we examined the impact of resveratrol on the same in vitro markers of
      endothelial and placental dysfunction following Nrf2 knockdown. RESULTS:
      Resveratrol significantly decreased placental oxidative stress and the production
      of sFlt1 and activin A. Resveratrol significantly mitigated tumor necrosis factor
      alpha stimulated endothelial expression of ICAM1, VCAM1, E-selectin and
      endothelin-1 and prevented an increase in endothelial monolayer permeability.
      Nrf2 knockdown abolished some of the protective effects of resveratrol on
      endothelial cells, but not in primary trophoblast cells. CONCLUSION: Features of
      placental and endothelial dysfunction characteristic of preeclampsia are improved
      by resveratrol in vitro, partially via the modulation of Nrf2.

PMID- 29208244
TI  - Role of nucleoside transporters in transplacental pharmacokinetics of nucleoside
      reverse transcriptase inhibitors zidovudine and emtricitabine.
AB  - INTRODUCTION: Zidovudine (AZT) and emtricitabine (FTC) are effective and well
      tolerated antiretroviral drugs, routinely used in the prevention of perinatal HIV
      transmission. However, precise mechanism(s) involved in their transfer from
      mother to fetus are not fully elucidated. Since both drugs are nucleoside
      analogues, we hypothesized that the mechanisms of their transplacental passage
      might include equilibrative nucleoside transporters, ENT1 and/or ENT2. METHODS:
      To address this issue, we performed in vitro accumulation assays in the BeWo
      placental trophoblast cell line, ex vivo uptake studies in fresh villous
      fragments isolated from human placenta and in situ dually perfused rat term
      placenta experiments. RESULTS: Applying this complex array of methods, we did not
      prove that ENTs play a significant role in transfer of AZT or FTC across the
      placenta. DISCUSSION: We conclude that the transplacental passage of AZT and FTC
      is independent of ENTs. Disposition of either compound into the fetal circulation
      should thus not be affected by ENT-mediated drug-drug interactions or placental
      expression of the transporters.

PMID- 29208245
TI  - Mammalian target of rapamycin signaling is a mechanistic link between increased
      endoplasmic reticulum stress and autophagy in the placentas of pregnancies
      complicated by growth restriction.
AB  - INTRODUCTION: Increased endoplasmic reticulum (ER) stress and autophagy have been
      noted in the placentas of pregnancies complicated by idiopathic intrauterine
      growth restriction (IUGR); however, the cause of these phenomena remains unclear.
      We surmised that oxygen-glucose deprivation (OGD) may increase ER stress and
      autophagy and that mammalian target of rapamycin (mTOR) signaling is involved in
      regulating placental ER stress and autophagy in pregnancies complicated by IUGR.
      METHODS: We obtained placentas from women with normal term pregnancies and
      pregnancies complicated by IUGR to compare ER stress, mTOR signaling, and levels
      of autophagy-related proteins between the two groups and used primary
      cytotrophoblast cells treated with or without salubrinal (an ER stress
      inhibitor), MHY1485 (an mTOR activator), or rapamycin (an mTOR inhibitor) to
      investigate the effects of OGD on ER stress, mTOR activity, and autophagy levels
      in vitro. RESULTS: Women with pregnancies complicated by IUGR displayed higher
      placental ER stress and autophagy levels but lower mTOR activity than women with
      normal pregnancies. Furthermore, OGD increased ER stress, regulated in
      development and DNA damage responses-1 (REDD1), phosphorylated tuberous sclerosis
      complex 2 (TSC2), and autophagy levels and decreased mTOR activity compared to
      the standard culture condition; however, the salubrinal treatment attenuated
      these changes. Moreover, the administration of MHY1485 or rapamycin to OGD
      treated cells decreased or increased autophagy levels, respectively. DISCUSSION:
      Based on our results, mTOR is a mechanistic link between OGD-induced ER stress
      and autophagy in cytotrophoblast cells; thus, mTOR plays an essential role in the
      pathogenesis of pregnancies complicated by IUGR.

PMID- 29208246
TI  - History of reptile placentology, part III: Giacomini's 1891 histological
      monograph on lizard placentation.
AB  - By the 1890s, placental arrangements had been documented macroscopically in
      lizards and fishes, but placental studies on such species lagged far behind
      research on mammals. In 1891, the biologist Ercole Giacomini (at the University
      of Siena, Italy) published the first histological analysis of a reptile placenta.
      Focusing on a placentotrophic lizard (Chalcides chalcides) with a morphologically
      complex placenta, Giacomini documented the histological and cellular bases for
      placental nutrient transfer and gas exchange. In conjunction with a follow-up
      study in 1906, he demonstrated that placental structure is correlated with
      function and can vary dramatically between related species. Giacomini's work was
      highly influential in showing that placentation in lizards had converged
      evolutionarily on that of mammals, while establishing reptile placentology as a
      highly promising area for future research.

PMID- 29208247
TI  - Assessing the Risk of Aortic Aneurysm in Takayasu Arteritis.

PMID- 29208248
TI  - Kidney Diseases Associated With Alternative Complement Pathway Dysregulation and
      Potential Treatment Options.
AB  - Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease
      and C3 glomerulonephritis) are characterized as inappropriate activation of the
      alternative complement pathway. Genetic mutations affecting the alternative
      complement pathway regulating proteins (complement factor H, I, membrane cofactor
      protein and complement factor H-related proteins) and triggers (such as
      infection, surgery, pregnancy and autoimmune disease flares) result in the
      clinical manifestation of these diseases. A decade ago, prognosis of these
      disease states was quite poor, with most patients developing end-stage renal
      disease. Furthermore, renal transplantation in these conditions was associated
      with poor outcomes due to graft loss to recurrent disease. Recent advances in
      targeted complement inhibitor therapy resulted in significant improvement in
      disease remission, renal recovery, health-related quality of life and allograft
      survival.

PMID- 29208249
TI  - Aortic Aneurysm in Takayasu Arteritis.
AB  - BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis
      (TA). This study aimed to evaluate the prevalence, clinical and imaging features,
      management and long-term outcomes of AA in patients with TA. MATERIALS AND
      METHODS: A retrospective study was performed of TA patients with AA admitted to
      Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA
      patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934
      patients with TA were identified with AA that was related to vasculitis. The mean
      age at disease onset was 31 +/- 10 years, with a female-to-male ratio of 1.79:1.
      The ascending aorta was the most common site of the aneurysmal lesion (18,
      33.3%), and the most frequent manifestations associated with AA were chest
      tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually
      concomitant with aortic valve insufficiency. Involvement of multiple sites in AA
      was found in 8 patients (20.5%), and multiple AAs were found in 5 patients
      (12.8%). No significant difference was observed in clinical and imaging findings
      between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient
      suffered from heart failure owing to perivalvular leakage, and 1 patient died,
      possibly related to severe complications of the operation. CONCLUSIONS: The
      prevalence of AA is relatively low in Chinese patients with TA. AA seems to
      develop more frequently in male patients with TA. Management should consider
      location and size of AA, complexity of vessel lesions and disease status. Long
      term follow-up is indispensable.

PMID- 29208250
TI  - Elevated Serum Midkine in Patients With Acute Pancreatitis.
AB  - BACKGROUND: Midkine (MK) is reported to be involved in the pathogenesis of
      numerous pathologies, but the expression of MK in acute pancreatitis (AP) has not
      been well studied and documented. METHODS: In this study, the temporal changes of
      serum MK were assessed in 97 patients with AP by enzyme-linked immunosorbent
      assay. RESULTS: The concentration of serum MK increased along with the severity
      of AP. Serum MK level increased more significantly in patients with organ failure
      than in those without organ failure. A more obvious elevation of serum MK level
      was also observed in patients with pancreatic necrosis. CONCLUSION: Serum MK
      might be a useful marker in the clinical diagnosis of AP.

PMID- 29208251
TI  - Drug-Coated Balloon Versus Drug-Eluting Stent in Primary Percutaneous Coronary
      Intervention: A Feasibility Study.
AB  - BACKGROUND: Drug-eluting stents (DES) represent a significant evolution in the
      treatment of patients with acute myocardial infarction with ST elevation.
      However, stent-related adverse events have led to an introduction of drug-coated
      balloons (DCB) applied particularly to bifurcation lesions, in-stent restenosis
      and small vessel disease. The aim of this study was to determine whether a DCB
      only strategy has a similar safety profile and equal angiographic and clinical
      outcomes to DES implantation in primary percutaneous coronary intervention
      (pPCI). MATERIALS AND METHODS: Seventy-five patients with acute myocardial
      infarction with ST elevation were randomized into DES and DCB groups of 37 and 38
      patients, respectively. The study end-points were major adverse cardiac events
      and late lumen loss during the 6 months following the pPCI. RESULTS: Reinfarction
      occurred in 5.4% of patients in the DES and 5.3% of patients in the DCB group
      after 1 month (risk ratio = 1.03, 95% CI [0.15-6.91], P = 0.98). After 6 months,
      major adverse cardiac events were reported in 5.4% of patients in the DES group
      and none in the DCB group (risk ratio = 5.13, 95% CI [0.25-103.42], P = 0.29).
      Late lumen loss in the DES group was 0.10 +/- 0.19mm and -0.09 +/- 0.09mm in the
      DCB group (P < 0.05). CONCLUSIONS: A DCB-only strategy is safe and feasible in
      the pPCI setting and showed good clinical and angiographic outcomes in a 6-month
      follow-up period.

PMID- 29208252
TI  - Sporadic Fundic Gland Polyps and Gastric Acid Suppression Level.
AB  - BACKGROUND: Fundic gland polyps (FGPs) are a common endoscopic finding and are
      known to be associated with proton pump inhibitors (PPIs) use. It is not known if
      their prevalence is affected by gastric acidity levels. This study aimed to
      assess whether there is a correlation between FGPs and gastric acidity levels as
      identified on 24-hour ambulatory impedance-pH studies in patients on PPI therapy.
      METHODS: We performed a review of 402 consecutive patients who take at least once
      daily PPI and underwent esophagogastroduodenoscopy with combined impedance-pH
      studies in the same setting (time and place) between January 2010 and December
      2014. Patients were classified into 2 groups based on the presence or absence of
      biopsy-confirmed FGPs during endoscopy. RESULTS: Of the 402 patients, 30 (7%) had
      FGPs. One of these polyps was found with low-grade dysplasia. There was no
      significant difference of the distributions of the [H+] in the FGPs versus the
      nonpolyp groups (P = 0.741). There was no significant difference between the 2
      groups regarding PPI dose frequency regimens (once and twice) (P = 0.074).
      However, we found weak ordinal association with PPI duration (P = 0.01) (Spearman
      = 0.1). CONCLUSIONS: FGPs are common endoscopic lesions. Incidence of dysplasia
      in FGPs is not only rare, but also of unknown clinical significance. Although
      they seem to be associated with PPIs, the mechanism remains unclear, as we found
      no correlation between the presence of FGPs and gastric acid control or PPI dose.
      Future studies would be useful to elucidate an alternate mechanism.

PMID- 29208254
TI  - Assessing Mobile Health Capacity and Task Shifting Strategies to Improve
      Hypertension Among Ghanaian Stroke Survivors.
AB  - BACKGROUND: There has been a tremendous surge in stroke prevalence in sub-Saharan
      Africa. Hypertension (HTN), the most potent, modifiable risk factor for stroke,
      is a particular challenge in sub-Saharan Africa. Culturally sensitive,
      efficacious HTN control programs that are timely and sustainable are needed,
      especially among stroke survivors. Mobile health (mHealth) technology and task
      shifting offer promising approaches to address this need. METHODS: Using a
      concurrent triangulation design, we collected data from stroke survivors,
      caregivers, community leaders, clinicians and hospital personnel to explore the
      barriers, facilitators and perceptions toward mHealth related to HTN management
      among poststroke survivors in Ghana. Exploration included perceptions of a nurse
      led navigational model to facilitate care delivery and willingness of stroke
      survivors and caregivers to use mHealth technology. RESULTS: Two hundred stroke
      survivors completed study surveys while focus groups (n = 4) were conducted with
      stroke survivors, caregivers and community leaders (n = 28). Key informant
      interviews were completed with clinicians and hospital personnel (n = 10). A
      total of 93% of survey respondents had HTN (60% uncontrolled). Findings support
      mHealth strategies for poststroke care delivery and HTN management and for task
      shifting through a nurse-led model. Of survey and focus group participants, 76%
      and 78.6%, respectively, have access to mobile phones and 90% express comfort in
      using mobile phones and conveyed assurance that task-shifting through a nurse-led
      model could facilitate management of HTN. Findings also identified barriers to
      care delivery and medication adherence across all levels of the social ecological
      model. CONCLUSIONS: Participants strongly supported enhanced care delivery
      through mobile health and were receptive toward a nurse-led navigational model.

PMID- 29208253
TI  - Socioeconomic, Psychosocial and Behavioral Characteristics of Patients
      Hospitalized With Cardiovascular Disease.
AB  - BACKGROUND: Recent studies have drawn attention to nonclinical factors to better
      understand disparities in the development, treatment and prognosis of patients
      with cardiovascular disease. However, there has been limited research describing
      the nonclinical characteristics of patients hospitalized for cardiovascular care.
      METHODS: Data for this study come from 520 patients admitted to the Duke Heart
      Center from January 1, 2015 through January 10, 2017. Electronic medical records
      and a standardized survey administered before discharge were used to ascertain
      detailed information on patients' demographic (age, sex, race, marital status and
      living arrangement), socioeconomic (education, employment and health insurance),
      psychosocial (health literacy, health self-efficacy, social support, stress and
      depressive symptoms) and behavioral (smoking, drinking and medication adherence)
      attributes. RESULTS: Study participants were of a median age of 65 years,
      predominantly male (61.4%), non-Hispanic white (67.1%), hospitalized for 5.11
      days and comparable to all patients admitted during this period. Results from the
      survey showed significant heterogeneity among patients in their demographic,
      socioeconomic and behavioral characteristics. We also found that the patients'
      levels of psychosocial risks and resources were significantly associated with
      many of these nonclinical characteristics. Patients who were older, women,
      nonwhite and unmarried had generally lower levels of health literacy, self
      efficacy and social support, and higher levels of stress and depressive symptoms
      than their counterparts. CONCLUSIONS: Patients hospitalized with cardiovascular
      disease have diverse nonclinical profiles that have important implications for
      targeting interventions. A better understanding of these characteristics will
      enhance the personalized delivery of care and improve outcomes in vulnerable
      patient groups.

PMID- 29208255
TI  - Using Ice Cream for Diagnosis of Diabetes Mellitus and Impaired Glucose
      Tolerance: An Alternative to the Oral Glucose Tolerance Test.
AB  - BACKGROUND: Oral glucose tolerance test (OGTT) is a sensitive and reliable test
      for diabetes mellitus and impaired glucose tolerance (IGT). However, poor patient
      tolerance of glucose solutions is common. We aim to compare the diagnostic value
      of an ice cream test with a standard OGTT. MATERIALS AND METHODS: A total of 104
      healthy adults were randomly assigned to either 75-g OGTT or ice cream, followed
      by a crossover to the other test. RESULTS: Most patients were females (71%). Mean
      age was 37 +/- 12 years, and body mass index was 24.2 +/- 3.9kg/m2. Diabetes
      mellitus and IGT, as diagnosed by 75-g OGTT, were 4.8% and 6.7%, respectively.
      The 2-hour plasma glucose levels were 110 +/- 55.5mg/dL with 75-g glucose and
      97.52 +/- 40.7mg/dL with ice cream. The correlation coefficient of 2-hour plasma
      glucose for the 2 tests was 0.82 (95% CI: 0.75-0.87; P < 0.001). Discordant
      diagnostic results, based on 2-hour plasma glucose levels, were 9.61%. By using a
      combination of fasting plasma glucose and 2-hour plasma glucose values, the ice
      cream test would have missed 5.76% of those at high risk for diabetes mellitus
      (impaired fasting glucose and IGT) or diabetes. CONCLUSIONS: An ice cream test
      may serve as an alternative to a 75-g OGTT. Before applying this test in clinical
      practice, it needs to be validated in a larger population.

PMID- 29208256
TI  - Combined Cryoballoon and Radiofrequency Ablation Versus Radiofrequency Ablation
      Alone for Long-Standing Persistent Atrial Fibrillation.
AB  - BACKGROUND: To achieve sinus rhythm, ablation of long-standing persistent atrial
      fibrillation (LSPAF) usually requires substrate modification in addition to
      pulmonary vein isolation (PVI). In the present article, we aimed to compare
      clinical and substrate modification effects of 2 distinct PVI strategies during
      stepwise ablation in patients with LSPAF: (1) Combined approach: cryoballoon (CB)
      for PVI and radiofrequency (RF) ablation for substrate modification and (2) RF
      only approach: RF ablation for both PVI and substrate modification. MATERIALS AND
      METHODS: A total of 34 patients were divided into 2 groups: 19 in the combined
      group and 15 in the RF group. Left atrial (LA) complex fractionated atrial
      electrogram (CFAE) maps were acquired before and after PVI and compared between
      groups. The groups were compared for acute atrial fibrillation termination (AFT)
      rates and long-term arrhythmia-free survival. RESULTS: A significant reduction on
      total LA CFAE area was observed with PVI in both groups. In the CB group, when
      pulmonary veins were excluded, the reduction of LA CFAE area was the most
      significant on the posterior wall of left atrium and which was greater than in
      the RF group. Although the ratio of AFT was higher in the CB group (44% versus
      33%, respectively), single-procedure arrhythmia-free survival at 1 year was
      comparable between groups (68% in the CB group versus 66% in the RF group). Times
      of total procedure, fluoroscopy and post-PVI RF were all shorter in the CB group.
      CONCLUSIONS: CB may cause greater substrate modification on the posterior wall
      and increase AFT rate during LSPAF ablation.

PMID- 29208257
TI  - Cross-Cultural Interprofessional Faculty Development in Japan: Results of an
      Integrated Workshop for Clinical Teachers.
AB  - BACKGROUND: Faculty development programs, studied both home and abroad, have been
      shown to be helpful for enhancing the scholarly and academic work of nonacademic
      clinicians. Interprofessional education and faculty development efforts have been
      less well studied. This project investigated the effect of a well-studied faculty
      development program applied in an interprofessional fashion across health
      profession educators in medicine and nursing. METHODS: A faculty cohort of nurse
      and physician educators at The University of Tokyo underwent training in the
      Stanford Faculty Development Center (SFDC) model of clinical teaching through a
      sequence of 7 workshops. The workshops were performed in English with all
      materials translated into Japanese. A validated, retrospective pretest and
      posttest instrument was used to measure study outcomes on global assessment of
      teaching abilities and specific teaching behaviors (STBs) at 1 and 12 months
      after intervention. Successful completion of Commitment to Change statements were
      also assessed at 12 months. RESULTS: In total, 19 faculty participants completed
      the study. All participants found the workshops valuable. For global assessment,
      significant improvement in self-reported teaching abilities was seen comparing
      the mean pretest scores of 27.26 (maximum score = 55, standard deviation [SD] =
      8.61) with mean scores at both 1 month (36.81, SD = 7.48, P < 0.001) and at 1
      year (34.67, SD = 7.32, P < 0.001). For STBs, significant improvement was also
      seen comparing the mean group pretest score of 82.11 (maximum score = 145, SD =
      15.72), to the posttest mean score of 111.11 (SD = 14.48, P < 0.001) and the 1
      year mean score of 103.76 (SD = 12.87, P < 0.001). In total, 27/42 Commitment to
      Change statements were successfully completed at 1 year. CONCLUSIONS: Faculty
      development for improving clinical teaching can be performed across the cultures
      of medicine and nursing, as well as across the cultures of the United States and
      Japan.

PMID- 29208258
TI  - Durability of Sirolimus for Lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting
      women of reproductive age, is characterized by cystic-appearing lung lesions,
      progressive loss of lung function, chylous effusions and renal angiomyolipomas.
      Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to
      stabilize lung function, reduce symptoms and resolve chylous effusions in the
      short term for patients with LAM. Herein, we report a premenopausal female with
      LAM who experienced complete and durable resolution of her chylothoraces with
      significant and sustained improvement in lung function on sirolimus.

PMID- 29208259
TI  - The Role of a Novel Long Noncoding RNA TUC40- in Cardiomyocyte Induction and
      Maturation in P19 Cells.
AB  - BACKGROUND: In previous studies, TUC40-, a new long noncoding RNA, was found to
      be overexpressed in human ventricular septal defect (VSD) embryonic heart
      samples. In this article, we carried out experiments on the P19 cell line to
      elucidate the effects of TUC40- overexpression on cardiomyocyte development
      relevant to VSD pathogenesis. METHODS: We established the overexpression cell
      model by plasmid transfection, and explored the expression profile of Pbx1, the
      sense gene of TUC40-, and the marker genes of cardiomyocyte linage commitment
      (Nkx2.5 and GATA4) and maturation (cardiac troponin T). In addition, we combined
      cell cycle and Cell Counting Kit-8 analysis to detect cell proliferation and used
      flow cytometry and caspase-3 assays to test apoptosis. At last, bioinformatics
      analysis was performed to show the possible role of TUC40-. RESULTS: In the
      control group, Pbx1 elevated steadily during cardiomyocyte induction; whereas in
      the overexpression group, it showed significantly lower expression at day 6, 8
      and 10 of induction. Cells in the overexpression group failed to induce
      cardiomyocytes indicated by GATA4 and cardiac troponin T. Proliferation was
      inhibited possibly owing to G2/M cell cycle arrest and the induced apoptosis rate
      was higher in the overexpression group. CONCLUSIONS: TUC40- overexpression
      reduced Pbx1 expression, cardiomyocyte induction and differentiation, inhibited
      proliferation and promoted apoptosis. Combining the results and previous studies,
      we propose TUC40- as a potential pathologic factor for VSD.

PMID- 29208260
TI  - Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.
AB  - BACKGROUND: This study aimed to confirm the ameliorative effect of ghrelin on
      asthma and investigate its mechanism. MATERIALS AND METHODS: The murine model of
      asthma was induced by ovalbumin (OVA) treatment and assessed by histological
      pathology and airway responsiveness to methacholine. The total and differential
      leukocytes were counted. Tumor necrosis factor alpha, interferon gamma,
      interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were
      quantified by commercial kits. The protein levels in pulmonary tissues were
      measured by Western blot analysis. RESULTS: Ghrelin ameliorated the histological
      pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse
      model. Consistently, OVA-increased total and differential leukocytes and levels
      of tumor necrosis factor alpha, interferon gamma, interleukin-5 and interleukin
      13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin.
      Ghrelin prevented the increased protein levels of the endoplasmic reticulum
      stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein
      homologous protein and reversed the reduced levels of p-Akt in asthmatic mice.
      CONCLUSIONS: Ghrelin might prevent endoplasmic reticulum stress activation by
      stimulating the Akt signaling pathway, which attenuated inflammation and
      ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy.

PMID- 29208261
TI  - Recurrent Malignancy-Associated Atypical Neutrophilic Dermatosis With
      Noninfectious Shock.
AB  - Sweet syndrome (SS) or acute febrile neutrophilic dermatosis presents with the
      sudden onset of fever, leukocytosis and tender, erythematous, edematous, well
      demarcated papules and plaques that histopathologically demonstrate a dense
      neutrophilic infiltrate. A total of 20% of patients with SS have malignancy
      associated disease that can present with bullous or atypical skin lesions that
      mimic pyoderma gangrenosum, another neutrophilic dermatosis. Both entities exist
      on a spectrum, and in the context of underlying malignancy, these neutrophilic
      diseases become less clinically distinct. The literature also describes life
      threatening cases of neutrophilic dermatoses that mimic severe sepsis. We present
      a fatal case of a patient with chronic eosinophilic leukemia with recurrent
      episodes of malignancy-associated atypical neutrophilic dermatosis characterized
      by necrotic skin lesions, pulmonary infiltrates and noninfectious shock and we
      also summarize the clinical presentations of an additional 10 patients reported
      in the literature. We conducted a PubMed search of articles published up to and
      in 2015, focusing on the English and Spanish literature with SS cross-referenced
      with the following search terms: neutrophilic dermatosis, pyoderma gangrenosum,
      shock, multiorgan failure and systemic inflammatory response syndrome. The
      articles were reviewed and the patients' clinical and laboratory findings were
      summarized. Cases of atypical neutrophilic dermatosis presenting with
      noninfectious shock syndrome are likely underrecognized clinically and
      underreported in the literature. Patients with malignancy-associated atypical
      neutrophilic dermatoses associated with noninfectious shock syndrome typically
      have multisystem disease characterized by recurrent episodes and typically have
      poor prognoses.

PMID- 29208262
TI  - Splenic Infarction and Rupture Due to Melioidosis.

PMID- 29208263
TI  - Nontyphoidal Salmonella Emphysematous Osteomyelitis.

PMID- 29208264
TI  - Spontaneous Pneumomediastinum in Dermatomyositis.

PMID- 29208265
TI  - Mulberry-Shaped Gingival Overgrowth Induced by Amlodipine and Cyclosporine.

PMID- 29208266
TI  - Comparative study of kerateine and keratose based composite nanofibers for
      biomedical applications.
AB  - In this work, two forms of keratins, kerateine (KR) and keratose (KO), were
      fabricated respectively into electrospun nanofibers by combination with
      polyurethane (PU). The differences of the structure and material properties
      between KR and KO based fibers were investigated by SEM observation, ATR-FTIR,
      XRD, contact angle, tensile test, in vitro degradation and cytocompatibility
      assay. The results indicated that the KR based nanofibers exhibited a higher
      tensile modulus, lower fracture strain and slower degradation rate, mainly due to
      the reformation of disulfide crosslinking between the regenerated cysteines in KR
      after the reductive extraction. The KO based nanofibers demonstrated a stronger
      hydrophilic property and higher water uptake ability due to the cysteic acid
      residues resulting from the oxidative extraction. Furthermore, the combination of
      keratins, regardless of KR or KO, could obviously improve the cytocompatibility
      of PU, especially in the cell attachment stage.

PMID- 29208267
TI  - Custom-made PEI/exfoliated-MoS2 nanocomposite ultrafiltration membranes for
      separation of bovine serum albumin and humic acid.
AB  - Herein, we report the effect of the exfoliated molybdenum disulfide (eMoS2)
      nanosheets in improving the permeability and anti-fouling properties of the PEI
      ultra-filtration (UF) membrane using bovine serum albumin (BSA) and humic acid
      (HA) as model fouling agents. The PEI/eMoS2 nanocomposite membranes were prepared
      via phase inversion method using three different eMoS2 concentrations (0.5, 1 and
      2wt%) designated as PEI-0.5, PEI-1 and PEI-2, respectively. Fourier transform
      infra-red spectroscopy employed to probe the surface functionalities on the
      membranes. Contact angle measurement, pure water flux, swelling rate and solute
      rejection studies confirmed the improved hydrophilicity of the PEI/eMoS2
      nanocomposite membranes than the individual entities. Flux recovery ratio (FRR),
      reversible and irreversible fouling results evidenced the improved fouling
      resistance of PEI/eMoS2 modified membranes than the individual counterparts. SEM
      results evidenced that the nanoscale eMoS2 significantly altered the membrane
      morphology by causing increased porosity and larger macrovoids formation on the
      surface as well as in the bulk of the membrane. PEI-1 membrane showed an
      increased pure water flux (52.54Lm-2h-1) and water content (74.8%) whereas lesser
      contact angle (69.2 degrees ) and hydraulic resistance (1.85kPa/Lm-2h-1).
      Resistance to fouling performance of PEI-1 membrane was evident from the FRR
      values of 95.3 and 90.2% and rejection values of 94.5 and 92.4% for BSA and HA
      respectively. PEI-2 membrane agglomerates with eMoS2 and hindered the membrane
      permeability by blocking the macrovoids in the bulk which restricted the
      permeation and fouling resistance of the membrane. Amongst various nanocomposite
      membranes investigated, the PEI-1 membrane exhibited better hydrophilicity and
      fouling resistance properties due to the availability of the favorable surface
      and bulk characteristics.

PMID- 29208268
TI  - Ultrafast microwave-assisted multicomponent tandem polymerization for rapid
      fabrication of AIE-active fluorescent polymeric nanoparticles and their potential
      utilization for biological imaging.
AB  - The fabrication and biomedical applications of fluorescent polymeric
      nanoparticles (FPNs) with aggregation-induced emission (AIE) feature has
      attracted the most intensive research interest since the first discovery of AIE
      phenomenon by Tang' group. Although great attention has been devoted to
      preparation of AIE-active FPNs, an efficient, facile and versatile strategy is
      still highly desirable to advance their biomedical applications. In this work, a
      one-pot microwave-assisted multicomponent tandem polymerization was proposed to
      fabricate AIE-active FPNs based on a microwave-assisted Kabachnik-Fields (KF)
      reaction, which involves the conjugation of aldehyde group containing
      polyethylene glycol (CHO-PEG-CHO) and amino-group terminating AIE dye (H2N-PhE
      NH2) using diethyl phosphate as the lock. The KF reaction can occur under rather
      facile and mild experimental conditions (e.g. absent of catalyst and solvents,
      air atmosphere) with the assistance of microwave irradiation in 5min. The
      resultant (PEG-DP-PhE) copolymers would self-assemble into FPNs that showed high
      water dispersibility and enhanced fluorescence intensity. The desirable
      cytocompatibility and cell uptake efficiency of PEG-DP-PhE FPNs endow their great
      potential for biomedical applications. Considering the convenience and
      effectiveness, the method should be promising for fabrication of many AIE-active
      functional materials with great application potential.

PMID- 29208269
TI  - High encapsulation and localized delivery of curcumin from an injectable
      hydrogel.
AB  - Most chemotherapy currently available for cancer treatment has limited potential
      to successful clinical cancer therapy, mainly due to low encapsulating capacity
      of drugs and unavailable pharmacologically beneficial concentrations at the tumor
      site. Herein, a novel yet simple strategy is developed to enhance drug
      encapsulating capacity and localized drug concentration using an injectable
      hydrogel based on thiolated chitosan (TCS) and poly(ethylene glycol) diacrylate
      (PEGDA). Almost 100% of encapsulating capacity is achieved when anti-cancer drug
      curcumin is encapsulated in the system. The interaction of curcumin with PEGDA is
      determined by fluorescence spectroscopy and the binding constant is calculated,
      followed by a simulation by a docking study using AutoDock. To improve the anti
      tumor activity and achieve effective local concentrations, lysozyme is introduced
      into the system. Sustained curcumin release in a controlled lysozyme-responsive
      behaviour is observed, which enables the drug concentration to reach the
      therapeutic threshold promptly. The system displays efficient intracellular
      curcumin release to promote cancer cells apoptosis in vitro. In addition, the
      system effectively delays the tumor growth and reduces adverse effects in tumor
      bearing nude mice. The strategy of localized, high encapsulation of drug by using
      an injectable hydrogel would be particularly beneficial with many insoluble anti
      cancer drugs.

PMID- 29208270
TI  - Nano-fibrous and ladder-like multi-channel nerve conduits: Degradation and
      modification by gelatin.
AB  - We recently fabricated multi-channel PLLA nerve conduits (NCs, conduits diameter:
      ~3mm, channels diameter: ~200MUm) with nano-fibrous microstructure (NNCs) and
      ladder-like microstructure (LNCs), and found the nanofibers in the NNCs promote
      differentiation of nerve stem cells (NSCs) into neurons. In the present study, we
      evaluated the degradation profile of NNCs and LNCs, and observed that NNCs
      degraded too fast to implant. To delay the degradation and retain the nano-scale
      effect of NNCs, we used gelatin to wrap (2% w/v gelatin) or embed (8% w/v
      gelatin) NNCs and LNCs via vacuum infusion and chemical cross-linking with
      genipin. NNCs-wrapped maintained their original nano-fibrous microstructure, but
      NNCs-embedded presented a porous morphology without nanofibers appearing.
      Incorporation of gelatin did not change their compressive moduli, but increased
      the creep recovery ratios of LNCs and NNCs. In vitro degradation revealed that
      integrity was maintained and the mass loss was <5% for NNCs-wrapped after
      10weeks, in comparison with 15% mass loss and collapsed structure of the pure
      NNCs after 4weeks. Meanwhile, there were no obvious changes in the degradation of
      LNCs with modification. Nerve stem cells (NSCs) were then seeded onto the six NCs
      represented as: NNCs, NNCs-wrapped, NNCs-embedded, LNCs, LNCs-wrapped, and LNCs
      embedded. Immunocytochemistry analysis demonstrated that gelatin coating enhanced
      the adhesion and proliferation of NSCs, and the NNCs-wrapped scaffold promoted
      the differentiation proportion of NSCs into neurons from 25.8% (on pure NNCs) to
      53.4% after 14days of seeding. On the other hand, only 14.3% of neurons were
      derived from the differentiation of the seeded NSCs on the NNCs-embedded. NNCs
      wrapped would be a good choice for future studies in nerve injury repair in vivo
      due to its appropriate degradation rate, flexibility, and nano-scale effect.

PMID- 29208271
TI  - Dissolvable layered microneedles with core-shell structures for transdermal drug
      delivery.
AB  - Microneedle (MN) systems for painless transdermal drug delivery have been
      developed in the past few years to overcome the issues of hypodermic injections.
      This study introduces a novel dissolvable layered microneedle (LMN) with core
      shell structure for efficient transdermal drug delivery. Fabricated by three-step
      casting method, the LMNs encapsulated the drug into the HA layer as a "shell",
      which is supported by PVA layer as core and base. When the LMNs are inserted into
      the skin, the drug would be released immediately once the HA layer were separated
      or dissolved. What's more, little drug would be wasted on the residual base after
      insertion. It is demonstrated that the mechanical property of LMNs is kept well
      with 100% insertion percentage at 60% relative humidity. Moreover, in the
      transdermal delivery in vivo test, almost 90% of drug in LMNs could be successful
      delivered into the skin with 10s, while the homogeneous HA MNs with wide drug
      distribution need more than 120s to reach the same efficiency. Owing to the
      advantages of stable mechanical property and rapid efficient drug delivery, the
      LMNs are more reliable and satisfied for the self-administration in the future.

PMID- 29208272
TI  - Biosynthesis of cerium oxide nanoparticles and their effect on lipopolysaccharide
      (LPS) induced sepsis mortality and associated hepatic dysfunction in male Sprague
      Dawley rats.
AB  - The fetal/life challenging Sepsis is an urgent medical disaster which have
      developed "blood poisoning". The sepsis is one of the disorders of organs which
      cause death in patients. The investigational models that mimicchemical change of
      sepsis in human bodywereessential. We have synthesized CeO2 NPs using eco
      friendly method using plant extract. The characterization of synthesized CeO2 NPs
      was studied using UV-Vis, FTIR, XRD, SEM, EDX and TEM analysis. The results were
      confirmed that the synthesized CeO2 was in nano size with spherical shape. The
      synthesized CeO2 nanoparticles were evaluated against lipopolysaccharide (LPS)
      male Sprague Dawley rats. We have intravenously administrated CeO2NPs (0.5mg/kg)
      to Sprague Dawleyratswhich are septic and checked the death rate, respiratory
      rate, blood pressure, body temperature. The rats could restore all parameters
      with decrease in hepatic damage, serum cytokines/chemokines, and swelling
      indicators. The Kupffer cells and macrophage cells treated with CeO2NPs and
      showed lowest TNF-a, IL-1b, IL-6, and HMGB1release. Due to the ROS, iNOS, COX-2,
      and nuclear factor-kappa light chain, the triggered B cells (NF-kB)
      transcriptional action was decreased. Thus, results represents that CeO2NPs can
      be applied as healing agent for liver sepsis.

PMID- 29208273
TI  - Self-catalyzed photo-initiated RAFT polymerization for fabrication of fluorescent
      polymeric nanoparticles with aggregation-induced emission feature.
AB  - In recent years, the fluorescent polymeric nanoparticles (FPNs) with aggregation
      induced emission (AIE) feature have been extensively exploited in various
      biomedical fields owing to their advantages, such as low toxicity,
      biodegradation, excellent biocompatibility, good designability and optical
      properties. Therefore, development of a facile, efficient and well designable
      strategy should be of great importance for the biomedical applications of these
      AIE-active FPNs. In this work, a novel method for the fabrication of AIE-active
      FPNs has been developed through the self-catalyzed photo-initiated reversible
      addition fragmentation chain transfer (RAFT) polymerization using an AIE dye
      containing chain transfer agent (CTA), which could initiate the RAFT
      polymerization under light irradiation. The results suggested that the final AIE
      active FPNs (named as TPE-poly(St-PEGMA)) showed great potential for biomedical
      applications owing to their optical and biological properties. More importantly,
      the method described in the work is rather simple and effective and can be
      further extended to prepare many other different AIE-active FPNs owing to the
      good monomer adoptability of RAFT polymerization.

PMID- 29208274
TI  - Hemostatic porous sponges of cross-linked hyaluronic acid/cationized dextran by
      one self-foaming process.
AB  - Effective hemostatic materials are very important for treating trauma cases.
      Natural polysaccharides have been particularly appealing in the development of
      new hemostatic materials due to their unique functions in human bodies. In this
      work, different polysaccharide-based hemostatic porous sponges (SHDP or SHDQ) of
      cross-linked hyaluronic acid (HA)/cationized dextran were readily prepared by the
      self-foaming process of HA and poly((2-dimethyl amino)-ethyl methacrylate)
      grafted dextran (Dex-PDM) or partially-quaternized Dex-PDM in the presence of
      sodium trimetaphosphate crosslinkers. SHDP and SHDQ sponges were investigated in
      terms of liquid-absorption ability, hemolysis, whole-blood clotting and
      hemostatic activity in hemorrhaging-liver models. Compared with HA/Dex-PDM
      sponges (HDP) without chemical cross-linking, SHDP and SHDQ sponges displayed
      higher porosity (>70.0% vs. 48.9%) and swelling ratios (>1000% vs. 520%).
      Meanwhile, hemolysis assay revealed the good blood compatibility of SHDP and SHDQ
      with low hemolysis ratio (below 0.5%). Furthermore, in vitro and in vivo
      hemostatic assay showed that SHDQ possessed better hemostatic properties than
      SHDP, owing to the higher cationic charges of partially-quaternized Dex-QPDM than
      Dex-PDM. The present study demonstrated that the self-foaming process of HA/Dex
      PDM under a 'green' condition is an effective means to produce new hemostatic
      materials.

PMID- 29208275
TI  - Synergetically understanding the interaction between nano/microspheres and
      peptide for controllable drug loading via experimental and theoretical
      approaches.
AB  - In this paper we systematically investigate the loading capacity of raspberry
      like nano/microspheres with highly cross-linked structure for the peptide,
      immunostimulating hexapeptide from human (IHH), by integrating both experimental
      and simulation efforts. The experimental results indicate that the loading
      capacities of raspberry-like nano/microspheres with different functionalized
      chains vary drastically. To provide theoretical insights into the observed
      phenomenon, the typical raspberry-like nano/microspheres were simplified as
      effective functionalized groups, thereby the interactions between them and IHH
      were accurately calculated by ab initio method. The ab initio results agree well
      with the experimental observations, and the underlying binding mechanism is
      analyzed in great details. It is shown that hydrogen bonding plays an important
      role and the binding affinity strongly depends on the functionalized motifs.
      Therefore, this work provides insightful guidance to controlling the drug loading
      by design of the functionalized surface of nanomaterials.

PMID- 29208276
TI  - Development of novel pH-sensitive thiolated chitosan/PMLA nanoparticles for
      amoxicillin delivery to treat Helicobacter pylori.
AB  - The cysteine conjugated chitosan/PMLA multifunctional nanoparticles were
      synthesized as targeted Nano-drug delivery system to eradicate Helicobacter
      pylori. Helicobacter pylori specifically express urea transport protein on its
      membrane to carrying urea to the cytoplasm urease to supply ammonia that protects
      bacteria in the acid environment of the stomach. The clinical suitability of
      topical antimicrobial agents is required to get rid of Helicobacter pylori inside
      the inflamed basal region. In this work, cysteine conjugated chitosan derivative,
      Cys-CS for their mucoadhesive and anticoagulant properties was designed and
      synthesized, for the preparation of multifunctional nanoparticles. The technique
      turned into optimized to prepare Cys-CS/PMLA nanoparticles for encapsulation of
      amoxicillin. The results showed that amoxicillin-Cys-CS/PMLA nanoparticles
      exhibit favorable pH-sensitive properties that could procrastinate the release of
      amoxicillin at gastric acid and allow the drug to deliver and target to
      Helicobacter pylori at its survival region efficiently. In comparison with
      unmodified amoxicillin-chitosan/PMLA nanoparticles, effective inhibition of
      Helicobacter pylori growth was observed for amoxicillin-Cys-CS/PMLA
      nanoparticles. These results indicate that the multifunctional amoxicillin-loaded
      nanoparticles have great potential for the effective treatment of Helicobacter
      pylori infection. They can also be used as pharmacologically powerful
      nanocarriers for oral targeted delivery of different therapeutic drugs to treat
      Helicobacter pylori.

PMID- 29208277
TI  - Preliminary investigation of the effect of doping of copper oxide in CaO-SiO2
      P2O5-MgO bioactive composition for bone repair applications.
AB  - A diopside based bioactive system with a nominal composition of xCuO-(45.55-x)CaO
      29.44 SiO2-10.28P2O5-14.73 MgO (x=0,1,3 and 5mol%) has been prepared by sol gel
      technique in the laboratory. X-ray Diffraction, Fourier Transform Infra-Red and
      Raman Spectroscopy, Field Emission Scanning Electron Microscopy along with Energy
      Dispersive X-ray Analysis and pH studies have been undertaken on the prepared
      samples before and after dipping the samples in simulated body fluid. It has been
      observed that hydroxyapatite layer starts to form with in 24h during immersion in
      simulated body fluid. Degradation studies have also been employed to check the
      degradation behavior in Tris-HCl. Dynamic light scattering studies show that
      particles are mostly agglomerated and have an average size of 356nm. Zeta
      potential studies have been undertaken to check the surface charge and it has
      been estimated that samples carry negative charge when dipped in simulated body
      fluid. Negative surface charge may contribute to attachment and proliferation of
      osteoblasts. Samples have also shown the antimicrobial properties against the
      Vibro cholerae and Escherichia coli pathogens. To check the non-toxic nature of
      the samples, cell cytotoxic and cell culture studies have been undertaken using
      the MG-63 cell lines. Samples have shown good response with good percentage
      viability of the cells in the culture media and hence, provides friendly
      environment to the growth of cells. The particle size, bioactivity, negative
      values of zeta potential, antimicrobial properties and good cell viability
      indicate the potential of the synthesized compositions as possible candidates for
      bone repair applications.

PMID- 29208278
TI  - Mixed-ligand copper(II) complex of quercetin regulate osteogenesis and
      angiogenesis.
AB  - Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)
      phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been
      synthesized and characterized. From the FT-IR spectroscopic studies, it was
      evident that C-ring of quercetin is involved in the metal chelation in all the
      three copper complexes. C-ring chelation was further proven by UV-Visible spectra
      and the presence of Cu(II) from EPR spectroscopic investigations. These complexes
      were found to have osteogenic and angiogenic properties, observed through in
      vitro osteoblast differentiation and chick embryo angiogenesis assay. In
      osteoblast differentiation, quercetin-Cu(II) complexes treatment increased
      calcium deposition and alkaline phosphatase activity (ALP) activity at the
      cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1
      collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt)
      showed more effects on osteoblast differentiation when compared to that of other
      two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to
      Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation
      was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The
      chick embryo angiogenesis assay showed that angiogenic parameters such as blood
      vessel length, size and junctions were stimulated by these complexes. Thus, the
      present study demonstrated that quercetin copper(II) complexes exhibit as a
      pharmacological agent for the orthopedic application.

PMID- 29208279
TI  - Collagen-alginate as bioink for three-dimensional (3D) cell printing based
      cartilage tissue engineering.
AB  - Articular cartilage repair is still a huge challenge for researchers and
      clinicians. 3D bioprinting could be an innovative technology for cartilage tissue
      engineering. In this study, we used collagen type I (COL) or agarose (AG) mixed
      with sodium alginate (SA) to serve as 3D bioprinting bioinks and incorporated
      chondrocytes to construct in vitro 3D printed cartilage tissue. Swelling ratio,
      mechanical properties, scanning electron microscopy (SEM), cell viability and
      cytoskeleton, biochemistry analysis and quantitative real-time polymerase chain
      reaction (qRT-PCR) were performed to investigate the function of different
      bioinks in 3D printing cartilage tissue engineering applications. The results
      showed that the mechanical strength was improved in both SA/COL and SA/AG groups
      compared to SA alone. Besides, the addition of COL or AG has little impact on
      gelling behavior, demonstrating the advantage as bioinks for 3D printing. Among
      the three scaffolds, SA/COL could distinctly facilitated cell adhesion,
      accelerated cell proliferation and enhanced the expression of cartilage specific
      genes such as Acan, Col2al and Sox9 than the other two groups. Lower expression
      of Col1a1, the fibrocartilage marker, was present in SA/COL group than that in
      both of SA and SA/AG groups. The results indicated that SA/COL effectively
      suppressed dedifferentiation of chondrocytes and preserved the phenotype. In
      summary, 3D bioprinted SA/COL with favorable mechanical strength and biological
      functionality is promising in cartilage tissue engineering.

PMID- 29208280
TI  - Formulation and biological actions of nano-bioglass ceramic particles doped with
      Calcarea phosphorica for bone tissue engineering.
AB  - The improvisation of the treatment procedures for treating the various kind of
      bone defects such as, bone or dental trauma and for diseases such as
      osteoporosis, osteomyelitis etc., need the suitable and promising biomaterials
      with resemblance of bone components. Bioactive glass ceramic (BGC) has recently
      acquired great attention as the most promising biomaterials; hence it has been
      widely applied as a filler material for bone tissue regeneration. Because it
      elicts specific biological responses after implantation in addition more
      potential in formation of strong interface with both hard and soft tissues by
      dissolution of calcium and phosphate ions. Hence, the current focus in treating
      the bone defects by orchestrating the biomaterial in combination of alternative
      medicine such as homeopathic remedies with biomaterials to prevent the adverse
      effects at minimal concentrations. So the current study was focused on
      constructing the nano-bioglass ceramic particles (nBGC) doped with novel
      homeopathic remedy Calcarea phosphorica for dental and bone therapeutic implants.
      The nBGC particles were synthesized by sol-gel method and reinforced with
      commercially available Calcarea phosphorica. The synthesized particles were
      characterized by SEM, DLS, EDS, FT-IR, and XRD studies. The SEM and DLS were
      shown the size of the particles at nano scale, also the EDS, and FT-IR
      investigations indicated that the Calcarea phosphorica was integrated with nBGC
      particles and also the crystalline nature of particles was confirmed by XRD
      studies. Both nBGC and Calcarea phosphorica doped nBGC (CP-nBGC) were found to be
      non toxic to mouse mesenchymal stem cells at lower concentrations and also
      illustrated the better bone forming ability in vitro.

PMID- 29208281
TI  - Overcoming STC2 mediated drug resistance through drug and gene co-delivery by PHB
      PDMAEMA cationic polyester in liver cancer cells.
AB  - Stanniocalcin 2 (STC2) overexpression in hepatocellular carcinoma (HCC) could
      lead to poor prognosis, which might be due to its induced P-glycoprotein and Bcl
      2 protein expression level increase. P-glycoprotein or membrane pump induced drug
      efflux and altered prosurvival Bcl-2 expression are key mechanisms for drug
      resistance leading to failure of chemotherapy in HCC. However, current strategy
      to overcome both P-glycoprotein and Bcl-2 protein induced drug resistance was
      rarely reported. In this work, we utilized an amphiphilic poly[(R)-3
      hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)
      cationic polyester to encapsulate chemotherapeutic paclitaxel (PTX) in
      hydrophobic PHB domain and Bcl-2 convertor Nur77/DeltaDBD gene (Nur77 without DNA
      binding domain for mitochondria localization) by formation of polyplex due to
      cationic PDMAEMA segment, to effectively inhibit the drug resistant HepG2/STC2
      and SMCC7721/STC2 liver cancer cell growth. Thanks to the cationic nanoparticle
      complex formation ability and high transfection efficiency to express Bcl-2
      conversion proteins, PHB-PDMAEMA/PTX@polyplex could partially impair P
      glycoprotein induced PTX efflux and activate the apoptotic function of previous
      prosurvival Bcl-2 protein. This is the pioneer report of cationic amphiphilic
      polyester PHB-PDMAEMA to codeliver anticancer drug and therapeutic plasmid to
      overcome both pump and non-pump mediated chemotherapeutic resistance in liver
      cancer cells, which might be inspiring for the application of polyester in
      personalized cancer therapy.

PMID- 29208282
TI  - Polyester micelles for drug delivery and cancer theranostics: Current
      achievements, progresses and future perspectives.
AB  - The development of tumor-targeting nanocarriers is critical important for
      effective treatment. The synthetic polyesters have demonstrated high potential
      for developing nanocarriers for cancer theranostics. Especially, the
      biocompatible and biodegradable polyester micelles have held great promise for
      cancer therapy and diagnosis, while some candidates have been translated into
      clinical applications or under clinical trial. In this review, we have provided
      the state-of-the-art of polyester micelles for drug delivery and cancer
      theranostics. In addition, we have summarized several major types of polyesters
      used in the biomedical fields, the current clinical achievements of polyester
      micelles and recent progresses of multi-functional polyester micelles for tumor
      molecular imaging and therapeutic applications.

PMID- 29208283
TI  - A review of recent progress in drug and protein encapsulation: Approaches,
      applications and challenges.
AB  - Many drugs and proteins formulated for treatment of various diseases are not
      fully utilised due to environmentally problems such as degradation by enzymes or
      it being hydrophobic. To counter this problem, the drug and protein of interest
      are encapsulated by synthetic polymers where they are protected from the
      environment. This allows the molecule to reach its target safely and maximise its
      function. In this paper, we will discuss about the different techniques of
      encapsulation that includes emulsion evaporation, self-emulsifying drug delivery
      system and supercritical fluid. This will be followed by the drugs and proteins
      that are commonly encapsulated to counter life-threatening diseases such as
      cancer and diabetes. A novel method using foam was proposed and will be briefly
      discussed as it can play a huge role in future developments.

PMID- 29208284
TI  - Corrigendum to "Liposome-based drug co-delivery systems in cancer cells" [Mater.
      Sci. Eng. C 71 (2017) 1327-1341].

PMID- 29208285
TI  - Hybrid nanofibers based on poly-caprolactone/gelatin/hydroxyapatite nanoparticles
      loaded Doxycycline: Effective anti-tumoral and antibacterial activity.
AB  - Cancer is one of the leading causes of morbidity and mortality Worldwide, 19.3
      million new cancer cases are expected to be identified in 2025. Among the
      therapeutic arsenal to cancer control one could find the Doxycycline and the nano
      hydroxyapatite. The Doxycycline (Dox) not only shown antibiotic effect but also
      exhibits a wide range of pleiotropic therapeutic properties as the control of the
      invasive and metastatic cancer cells characteristics. The purpose of the present
      study was to evaluate both cytotoxicity in vitro and antibacterial activity of
      electrospun Dox-loaded hybrid nanofibrous scaffolds composed by hydroxyapatite
      nanoparticles (nHA), poly-epsilon-caprolactone (PCL) and gelatin (Gel) polymers.
      Both nHA and Dox were dispersed into different PCL/Gel ratios (70:30, 60:40,
      50:50wt%) solutions to form electrospun nanofibers. The nHA and Dox/nHA/PCL-Gel
      hybrid nanofibers were characterized by TEM microscopy. In vitro Dox release
      behavior from all of these Dox-loaded nHA/PCL-Gel nanofibers showed the same
      burst release profile due to the high solubility of Gel in the release medium.
      Antibacterial properties of nanofiber composites were evaluated using Gram
      positive Staphylococcus aureus (S. aureus) and Gram-negative Porphyromonas
      gingivalis (P. gingivalis) bacteria. The co-delivery of nHA particles and Dox
      simultaneously exhibited inhibition of bacterial growth more efficiently than the
      delivery of either Dox or nHA at the same concentrations, indicating a
      synergistic effect. The results showed that cancer cell tested had different
      sensibility to co-delivery system. On the whole, A-431 cells were found exhibited
      the most pronounced synergistic effect compared to CACO-2 and 4T1 cancer cells.
      Based on the anticancer as well as the antimicrobial results in this study, the
      developed Dox/nHA/PCL-Gel composite nanofibers are suitable as a drug delivery
      system with potential applications in the biomedical fields.

PMID- 29208286
TI  - One pot biocatalytic synthesis of a biodegradable electroactive macromonomer
      based on 3,4-ethylenedioxytiophene and poly(l-lactic acid).
AB  - A novel electroactive macromonomer based on poly(l-lactic acid) (PLLA) with (3,4
      ethylenedioxythiophene) (EDOT) functional end groups, was prepared by a
      traditional approach of organometallic polymerization with stannous octanoate
      [Sn(oct2)] and enzymatic polymerization using immobilized Candida antarctica
      Lipase B (CAL-B) and Amano lipase Pseudomonas cepacia(PS-IM), as catalysts. In
      the synthetic strategy, (2,3-dihydrothieno[3,4-b] dioxin-2-yl)methanol (EDOT-OH)
      was used to initiate the ring opening polymerization of lactide to yield PLLA
      with EDOT end group. All macromonomers (EDOT-PLLA) were characterized by 1H and
      13C RMN, MALDI-TOF, GPC and EDX. Moreover, ICP-OES analysis showed the presence
      of Sn traces in the material synthesized by the traditional approach, but that
      pathway led to macromonomers with higher molecular weight while the enzymatic
      route led to completely metal-free macromonomers with medium and lower molecular
      weights. Also, electrochemical and chemical polymerization of EDOT-PLLA were
      tested showing that it is possible to prepare degradable conducting polymers
      based on poly(3,4-ethylenedioxythiphene) (PEDOT). The biocatalytic synthesis is a
      very promising and environmental friendly pathway for the preparation of
      biodegradable materials for short time applications.

PMID- 29208287
TI  - Development of temozolomide coated nano zinc oxide for reversing the resistance
      of malignant glioma stem cells.
AB  - Recently most of the researchers have turned their interest towards plant
      mediated synthesis of metal nanoparticles to avoid several environmental
      toxicants. In this manuscript, we have discussed the ecofriendly syntheses of
      zinc oxide nanoparticles (ZnO NPs) were achieved using Glycyrrhiza glabra (G.
      glabra) seed aqueous extract. The green synthesized ZnO NPs were characterized
      using analytical techniques like XRD, TEM, particle size histogram and Zeta
      potential. From the results, it was found that the green synthesized ZnO NPs were
      around 35nm in size with irregular spherical shape. The Zeta potential study of
      ZnO NPs was resulted to be high stabile with electronegative charge around 
      56.3mV. Further the G. glabra seed aqueous extract mediated synthesis of ZnO NPs
      were subjected to treat human glioblastoma cells with the help of temozolomide
      (TMZ) a commercially available drug by the method of MTT cell viability assay.
      The results stated that the ZnO NPs shows IC50 value around 30MUg/mL results
      significantly. The plausible mechanism behind the mortality rate was also
      discussed in this manuscript.

PMID- 29208288
TI  - Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry
      optimization with a mechanobiology - driven algorithm.
AB  - In a context more and more oriented towards customized medical solutions, we
      propose a mechanobiology-driven algorithm to determine the optimal geometry of
      scaffolds for bone regeneration that is the most suited to specific boundary and
      loading conditions. In spite of the huge number of articles investigating
      different unit cells for porous biomaterials, no studies are reported in the
      literature that optimize the geometric parameters of such unit cells based on
      mechanobiological criteria. Parametric finite element models of scaffolds with
      rhombicuboctahedron unit cell were developed and incorporated into an
      optimization algorithm that combines them with a computational mechanobiological
      model. The algorithm perturbs iteratively the geometry of the unit cell until the
      best scaffold geometry is identified, i.e. the geometry that allows to maximize
      the formation of bone. Performances of scaffolds with rhombicuboctahedron unit
      cell were compared with those of other scaffolds with hexahedron unit cells. We
      found that scaffolds with rhombicuboctahedron unit cell are particularly suited
      for supporting medium-low loads, while, for higher loads, scaffolds with
      hexahedron unit cells are preferable. The proposed algorithm can guide the
      orthopaedic/surgeon in the choice of the best scaffold to be implanted in a
      patient-specific anatomic region.

PMID- 29208289
TI  - Elastic polyurethane bearing pendant TGF-beta1 affinity peptide for potential
      tissue engineering applications.

PMID- 29208290
TI  - Synthesis, spectroscopic, thermal and molecular modeling studies of Zn2+, Cd2+
      and UO22+ complexes of Schiff bases containing triazole moiety. Antimicrobial,
      anticancer, antioxidant and DNA binding studies.
AB  - A novel series of Zn2+, Cd2+ and UO22+ complexes of ligands namely 1-[(5-mercapto
      1H-1,2,4-triazole-3-ylimino) methyl]naphthalene-2-ol (HL1) and [(1H-1,2,4
      triazole-3-ylimino) methyl] naphthalene-2-ol (HL2) have been prepared and
      characterized by different analytical and spectral techniques. The stoichiometry,
      stereochemistry, conductivity measurements and mode of bonding of the complexes
      have been elucidated. Accurate comparison of the IR spectra of the ligands with
      their metal chelates proved the involvement of nitrogen atoms of the azomethine
      group and/or triazole ring in chelation in addition to the deprotonated hydroxyl
      oxygen. The UV-Vis and molar conductance data supported the octahedral geometry
      for the metal complexes. TGA technique has been used to study the thermal
      decomposition way of the metal complexes and the thermo kinetic parameters were
      estimated. Valuable information is obtained from calculations of molecular
      parameters using the molecular modeling techniques. The interaction between the
      metal complexes and CT-DNA has been studied from which the binding constants (kb)
      were calculated. The Schiff bases and their metal chelates have shown potent
      antimicrobial, antioxidant and antitumor activities. The antitumor activities of
      the compounds have been tested in vitro against HEPG2 cell line and in silico by
      the molecular docking analysis with the VEGFR-2 receptor responsible for
      angiogenesis.

PMID- 29208291
TI  - Optimization of the composition and dosage of PEGylated polyethylenimine
      entrapped gold nanoparticles for blood pool, tumor, and lymph node CT imaging.
AB  - Gold nanoparticles (Au NPs) with a high X-ray attenuation coefficient have a good
      potential in CT imaging applications. Here, we report the design and synthesis of
      Au NPs entrapped within polyethylene glycol (PEG)-modified branched
      polyethyleneimine (PEI) with varying the initial Au salt/PEI molar ratios and
      with the remaining PEI surface amines being acetylated for blood pool, lung tumor
      and lymph node CT imaging. The formed unacetylated and acetylated PEGylated PEI
      entrapped Au NPs (Au PENPs) were characterized via different methods. We show
      that the PEGylated PEI is an effective template to entrap Au NPs having a uniform
      size ranging from 1.7nm to 4.4nm depending on the Au salt/PEI molar ratio. After
      optimization of the composition-dependent X-ray attenuation effect, we then
      selected {(Au0)100-PEI.NHAc-mPEG} NPs for biological testing and show that the
      particles have good cytocompatibility in the given concentration range and can be
      used as a contrast agent for effective CT imaging of the blood pool of rats, lung
      cancer model of nude mice and lymph node of rabbits after intravenous injection.
      For each application, the injected dosage of the particles was optimized. In
      addition, the {(Au0)100-PEI.NHAc-mPEG} NPs could be excreted out of the body with
      time. Our results indicate that the formed Au PENPs with an appropriate
      composition and dosage hold a great promise to be used for CT imaging of various
      biosystems.

PMID- 29208292
TI  - Hydroxyapatite/mesoporous silica coated gold nanorods with improved degradability
      as a multi-responsive drug delivery platform.
AB  - In this study, gold nanorods/mesoporous silica/hydroxyapatite (Au/SiO2/HAP)
      hybrid nanoparticles with AuNR core and SiO2/HAP hybrid inorganic shell for multi
      responsive drug delivery had been prepared. The morphology and structure of the
      nanoparticles were characterized by TEM, XPS, XRD, FT-IR and N2 adsorption
      desorption isotherms. The degradation of the hybrid nanoparticles could be
      significantly improved by the dissolution of HAP from the hybrid skeleton in acid
      environment. In vitro drug release results indicated that Au/SiO2/HAP
      nanoparticles exhibited high drug loading efficiency, excellent near-infrared
      (NIR)- and pH-responsive drug release properties. Compared to the drug release of
      Au/SiO2 nanoparticles over 12h (about 6.35%), Au/SiO2/HAP nanoparticles displayed
      a higher drug release of 37.62% upon NIR irradiation at pH4.5 due to the NIR
      responsiveness of AuNRs and the pH-responsiveness of HAP in acid media. The cell
      viability results also indicated that the Au/SiO2/HAP nanoparticles exhibited the
      excellent biocompatibility. The present paper provides a facile route to
      fabricate a hybrid drug carrier with high drug loading efficiency, excellent pH
      sensitivity, NIR-sensitivity, biodegradability and biocompatibility.

PMID- 29208293
TI  - Mesoporous silica-based bioactive glasses for antibiotic-free antibacterial
      applications.
AB  - Bioactive glasses (BGs) are being used in several biomedical applications, one of
      them being as antibacterial materials. BGs can be produced via melt-quenching
      technique or sol-gel method. Bactericidal silver-doped sol-gel derived mesoporous
      silica-based bioactive glasses were reported for the first time in 2000, having
      the composition 76SiO2-19CaO-2P2O5-3Ag2O (wt%) and a mean pore diameter of 28nm.
      This review paper discusses studies carried out exploring the potential
      antibacterial applications of drug-free mesoporous silica-based BGs. Bioactive
      glasses doped with metallic elements such as silver, copper, zinc, cerium and
      gallium are the point of interest of this review, in which SiO2, SiO2-CaO and
      SiO2-CaO-P2O5 systems are included as the parent glass compositions. Key findings
      are that silica-based mesoporous BGs offer a potential alternative to the
      systemic delivery of antibiotics for prevention against infections. The
      composition dependent dissolution rate and the concentration of the doped
      elements affect the antibacterial efficacy of BGs. A balance between
      antibacterial activity and biocompatibility is required, since a high dose of
      metallic ion addition can cause cytotoxicity. Typical applications of mesoporous
      BGs doped with antibacterial ions include bone tissue regeneration,
      multifunctional ceramic coatings for orthopedic devices and orbital implants,
      scaffolds with enhanced angiogenesis potential, osteostimulation and
      antibacterial properties for the treatment of large bone defects as well as in
      wound healing.

PMID- 29208294
TI  - Hearing loss: time for sound action.

PMID- 29208295
TI  - Far from universal access to electricity.

PMID- 29208296
TI  - Crucial role of finance ministry in achieving universal health coverage.

PMID- 29208297
TI  - Women in science, medicine, and global health: call for papers.

PMID- 29208298
TI  - Offline: The latent power of doctors.

PMID- 29208299
TI  - Informing women with endometriosis about ovarian cancer risk.

PMID- 29208300
TI  - To be a scientist in Mexico... or not to be?

PMID- 29208301
TI  - A global perspective on the history of anaesthesia.

PMID- 29208302
TI  - Efficacy of infliximab biosimilars in patients with Crohn's disease.

PMID- 29208304
TI  - Efficacy of infliximab biosimilars in patients with Crohn's disease - Authors'
      reply.

PMID- 29208303
TI  - Efficacy of infliximab biosimilars in patients with Crohn's disease.

PMID- 29208305
TI  - Heart transplantation at 50.

PMID- 29208306
TI  - US Senate considers Alex Azar to lead HHS.

PMID- 29208307
TI  - Department of Error.

PMID- 29208308
TI  - Serum intestinal fatty-acid binding protein: predictor of bowel necrosis in
      pediatric intussusception.
AB  - BACKGROUND/PURPOSE: Serum Intestinal Fatty-Acid Binding Protein (I-FABP) is a
      useful marker of bowel necrosis in pediatric intussusception. The aim of this
      study is to determine the sensitivity of this marker and correlate it with length
      of necrosed small bowel. METHODS: A single-centre prospective study of 50
      children presenting to Lagos University Teaching Hospital, Nigeria, in whom a
      diagnosis of intussusception was made over 1 year was completed. Additionally, 25
      age- and sex-matched controls (day case surgery) were recruited. They were
      grouped into three: 25 children with necrotic bowel, 25 without bowel necrosis,
      and 25 controls. The serum IFABP levels were compared between the cohorts with
      confirmed bowel necrosis at surgery and those with no necrosis, as well as
      controls. The cut-off values for the diagnosis of bowel necrosis were calculated
      using a receiver operating characteristic curve (ROC). The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      were calculated. RESULTS: Twenty-five children were diagnosed with necrotic
      intussusception whose serum IFABP immunoassay has significantly higher median
      compared with those without necrosis and controls (2056.0ng/ml vs. 943.0ng/ml and
      478.0ng/ml P=0.0002). Using a cut-off value of 1538ng/ml, the sensitivity,
      specificity, PPV, and NPV were 64%, 88%, 84%, and 71%, respectively. I-FABP titer
      greater than 1538ng/ml was found to have higher likelihood of necrotic bowel
      (p=0.002; odds ratio 13.04; 95% confidence interval; 0.618-0.891). CONCLUSION:
      Serum I-FABP is moderately sensitive for discriminating between bowel necrosis,
      and it predicts increased likelihood of bowel resectability in intussusception.
      LEVEL OF EVIDENCE: Level II - Development of diagnostic criteria in a consecutive
      series of patients and a universally applied "gold standard".

PMID- 29208309
TI  - Detection of estrogen active compounds in hops by planar yeast estrogen screen.
AB  - Hops used in the brewing process of beer for flavoring are known to contain
      estrogen active compounds (EAC) and to be the source of EAC in beer. The recently
      developed planar yeast estrogen screen (pYES) with the substrate resorufin-beta-d
      galactopyranoside (RGP) successfully was applied for the detection of EAC in
      ethanolic extracts of hops pellet samples. The only pYES positive compound was
      identified as the hop flavanone prenylnaringenin (PN) by thin-layer
      chromatography-mass spectrometry. The heat-induced formation of estrogen active
      PN from the inactive hop flavonoid desmethylxanthohumol was confirmed by
      simulation of wort boiling, extraction of both the hops' remainder and the
      supernatant water, and subsequent investigation of the extracts by pYES. By means
      of the dose-response curve of PN of a hops' remainder extract, the estradiol
      equivalent concentration (EEQ) and thus the estradiol equivalent amount (EEA) of
      PN in the hops' remainder after simulation of the wort boiling was determined to
      39 MUg/L and 52 MUg/kg, respectively.

PMID- 29208310
TI  - Equivalent mortality and complication rates following periprosthetic distal femur
      fractures managed with either lateral locked plating or a distal femoral
      replacement.
AB  - INTRODUCTION: Management of distal femur fractures above total knee arthroplasty
      (TKA) remains challenging. Two common surgical options are locked lateral plating
      (LLP) and distal femoral arthroplasty (DFR). Unfortunately, approximately 30-50%
      of patients may die within one year of injury, require further surgery, or not
      regain prior mobility performance. We compared 87 LLP to 53 DFR patients - to our
      knowledge the largest comparative study - focusing on 90- and 365-day mortality,
      mobility maintenance, and further surgery. METHODS: We performed a retrospective
      review of patients at least 55 years old who sustained femur fractures near a
      primary TKA (essentially OTA-33 or Su types 1, 2, or 3) from 2000 to 2015
      assigning cohort based on treatment: LLP or DFR. We excluded patients having
      prior care for the injury, whose surgery was not for fracture (e.g. loosening),
      or having other surgical intervention (e.g. intramedullary nail). RESULTS:
      Results Cohorts were similar based on body mass index and age adjusted Charlson
      Comorbidity Index (aaCCI). LLP was more common than DFR for fractures above and
      at the level of the implant, but similar for fractures within the implant for
      patients with aaCCI >= 5. LLP and DFR had similar mortality at 90 days (9% vs 4%)
      and 365 days (22% vs 10%), need for additional surgery (9% vs 3%), and survivors
      maintaining ambulation (77% vs 81%). Patients whose surgery occurred 3 or more
      days after presentation had similar mortality risk to those whose surgery was
      before 3days. The mean age of one year survivors was 77 whereas for patients who
      died it was 85. Neither surgical choice nor aaCCI was associated with increased
      risk in time to surgery. CONCLUSIONS: Fracture location, remaining bone stock,
      and patient's prior mobility and current comorbidities must guide treatment. Our
      study suggests that 90- and 365-day mortality, final mobility, and re-operation
      rate are not statistically different with LLP vs DFR management.

PMID- 29208311
TI  - Bonding strategies for MIH-affected enamel and dentin.
AB  - OBJECTIVES: Aim of the present study was to evaluate resin composite adhesion to
      dental hard tissues affected by molar incisor hypomineralisation (MIH). METHODS:
      94 freshly extracted human molars and incisors (53 suffering MIH) were used. 68
      teeth (35 with MIH) were used for MU-TBS tests in enamel and dentin, 26 (18 with
      MIH) for qualitative evaluation. Specimens were bonded with Clearfil SE Bond,
      Scotchbond Universal, and OptiBond FL. For MIH affected enamel, additional
      OptiBond FL groups with NaOCl and NaOCl+Icon were investigated. Beside
      fractographic analysis, also qualitative evaluations were performed using SEM at
      different magnifications as well as histological sectioning. RESULTS: Highest MU
      TBS values were recorded with dentin specimens (ANOVA, mod. LSD, p<0.05). Results
      were independent of adhesive and dentin substrate (p>0.05). Pre-test failures did
      not occur in dentin specimens. Sound enamel specimens exhibited significantly
      higher MU-TBS values than MIH enamel (p<0.05). The two-step self-etch adhesive
      (Clearfil SE Bond) and the two-step etch-and-rinse adhesive (Scotchbond
      Universal) showed the lowest values in affected enamel specimens (p<0.05) with
      most pre-test failures (p<0.05). OptiBond FL on affected enamel showed better
      results than Clearfil SE Bond (p<0.05). An additional pre-treatment of affected
      enamel with NaOCl or NaOCl and Icon did not enhance enamel bonding (p>0.05),
      however, it caused less pre-test failures (p<0.05). Micromorphological analyses
      revealed that conventional phosphoric acid etching produces a much less
      pronounced etching pattern in affected enamel and a porous structure as weak link
      for the resin-enamel bond was identified. SIGNIFICANCE: Bonding to porous
      hypomineralized MIH enamel is the limiting factor in adhesion to MIH teeth. MIH
      affected dentin may be bonded conventionally.

PMID- 29208312
TI  - Gadolinium deposition in the paediatric brain: T1-weighted hyperintensity within
      the dentate nucleus following repeated gadolinium-based contrast agent
      administration.
AB  - AIM: To determine whether repeated gadolinium-based contrast agent administration
      (GBCA) in children is associated with the development of increased T1-weighted
      signal intensity within the cerebellar dentate nucleus. MATERIALS AND METHODS:
      With institutional review board approval for this The Health Insurance
      Portability and Accountability Act-compliant retrospective study, a cohort of 41
      patients under the age of 18 years who underwent at least four contrast-enhanced
      magnetic resonance imaging (MR) examinations of the brain from 2005 to 2015 were
      identified. For each examination, both dentate nuclei were manually contoured,
      and the mean dentate nucleus-to-pons signal intensity (DN-P SI) ratio was
      calculated. The DN-P SI ratios from the last to first MRI examination were
      compared, and the correlation between DN-P SI ratio and cumulative gadolinium
      dose was calculated using a linear mixed effect model to control for potentially
      confounding variables. RESULTS: For the 41 patients in the cohort, there was a
      significant increase in the mean DN-P SI ratio from the first MRI to the last MRI
      examination (1.05 versus 1.11, p=0.004). After controlling for patient diagnosis,
      history of chemotherapy or radiation, sex, and age, there was a significant
      positive association between DN-P SI ratio and cumulative gadolinium dose
      (coefficient=0.401, p=0.032). CONCLUSION: Repeated GBCA administration in
      children is associated with increased T1-weighted signal intensity within the
      dentate nucleus.

PMID- 29208313
TI  - Pursuit of a method for single administration of pFSH for superstimulation in
      cattle: What we have learned.
AB  - A single dose protocol of FSH for superstimulation in cattle may improve
      compliance and superovulatory response. A single subcutaneous (sc) administration
      of pFSH was efficacious, but response depended on body condition and injection
      site; the adipose tissue pad behind the shoulder was most efficacious.
      Inconsistent results in Holsteins were partially overcome by sc administration of
      75% of the total pFSH dose behind the shoulder on the first day followed by 25%
      48 h later. An alternative would be to combine FSH with polymers that cause it to
      be released slowly over several days. Hyaluronan is found normally in most animal
      tissues and is nonreactive when administered parentally. A single intramuscular
      (im) administration of pFSH in a 2.0% hyaluronan induced a superovulatory
      response that did not differ from twice daily im administration over 4 d.
      However, 2.0% hyaluronan was viscous and difficult to mix with FSH. Although
      solutions of 1.0 and 0.5% hyaluronan were less viscous, they lacked efficacy as a
      single im administration. However, superovulatory response was high when either
      1.0 or 0.5% hyaluronan was used in a two-dose im protocol; two-thirds on the
      first day and one-third 48 h later. A single im administration of FSH in 0.5%
      hyaluronan effectively induced superstimulation for OPU in cattle. Successful
      superovulation in the cow was associated with circulating FSH levels that were
      similar to endogenous FSH levels prior to follicular wave emergence; however,
      levels must be maintained above baseline for at least 72 h, or 36 h for OPU.
      Circulating FSH levels following a single sc administration of 400 mg NIH-FSH-P1
      behind the shoulder in beef cows increased to 1.0 or 1.2 ng/mL at 12 h and were
      back near baseline in approximately 60 h, while FSH levels following im
      administration of 200 mg NIH-FSH-P1 in 0.5% hyaluronan into Holstein donors
      reached 1.5 ng/mL at 12 h and returned to baseline in approximately 36 h.

PMID- 29208314
TI  - The 20S immunoproteasome and constitutive proteasome bind with the same affinity
      to PA28alphabeta and equally degrade FAT10.
AB  - The 20S immunoproteasome (IP) is an interferon(IFN)-gamma - and tumor necrosis
      factor (TNF) -inducible variant of the 20S constitutive proteasome (CP) in which
      all its peptidolytically active subunits beta1, beta2, and beta5 are replaced by
      their cytokine inducible homologues beta1i (LMP2), beta2i (MECL-1), and beta5i
      (LMP7). These subunit replacements alter the cleavage specificity of the
      proteasome and the spectrum of proteasome-generated peptide ligands of MHC class
      I molecules. In addition to antigen processing, the IP has recently been shown to
      serve unique functions in the generation of pro-inflammatory T helper cell
      subtypes and cytokines as well as in the pathogenesis of autoimmune diseases, but
      the mechanistic involvement of the IP in these processes has remained elusive. In
      this study we investigated whether the IP differs from the CP in the interaction
      with two IFN-gamma/TNF inducible factors: the 11S proteasome regulator
      PA28alphabeta and the ubiquitin-like modifier FAT10 (ubiquitin D). Using
      thermophoresis, we determined the affinity of PA28alphabeta for the CP and IP to
      be 12.2nM +/- 2.8nM and 15.3nM +/- 2.7nM, respectively, which is virtually
      identical. Also the activation of the peptidolytic activities of the IP and CP by
      PA28alphabeta did not differ. For FAT10 we determined the degradation kinetics in
      cycloheximide chase experiments in cells expressing almost exclusively IP or CP
      as well as in IFN-gamma stimulated and unstimulated cells and found no
      differences between the degradation rates. Taken together, we conclude that
      neither differences in the binding strength to, nor activation by PA28alphabeta,
      nor a difference in the rate of FAT10-mediated degradation can account for
      distinct functional capabilities of the IP as compared to the CP.

PMID- 29208315
TI  - On the role of V1 in avoiding obstacles.

PMID- 29208316
TI  - Should we perform an inspiratory or an expiratory chest radiograph for the
      initial diagnosis of pneumothorax?
AB  - Chest radiography for pneumothorax screening is a frequently employed test.
      However, there is some controversy about which radiographic technique to choose.
      Posteroanterior chest radiography taken during expiration has been the technique
      used for many decades because several experts in classical thoracic radiology,
      such as Greene and Felson, recommended it. However, chest radiography, with
      posteroanterior and lateral projections, taken during deep breath is the
      appropriated technique to initially assess the whole thoracic pathology. In this
      review we have tried to establish, based on the best available evidence, which is
      the initial examination of choice to diagnose pneumothorax.

PMID- 29208317
TI  - Protein dynamics in the solid-state from 2H NMR lineshape analysis. III. MOMD in
      the presence of Magic Angle Spinning.
AB  - We report on a new approach to the analysis of dynamic NMR lineshapes from
      polycrystalline (i.e., macroscopically disordered) samples in the presence of
      Magic Angle Spinning (MAS). This is an application of the Stochastic Liouville
      Equation developed by Freed and co-workers for treating restricted (i.e.,
      microscopically ordered) motions. The 2H nucleus in an internally-mobile C-CD3
      moiety serves as a prototype probe. The acronym is 2H/MOMD/MAS, where MOMD stands
      for "microscopic-order-macroscopic-disorder." The key elements describing
      internal motions - their type, the local spatial restrictions, and related
      features of local geometry - are treated in MOMD generally, within their rigorous
      three-dimensional tensorial requirements. Based on this representation a single
      physically well-defined model of local motion has the capability of reproducing
      experimental spectra. There exist other methods for analyzing dynamic 2H/MAS
      spectra which advocate simple motional modes. Yet, to reproduce satisfactorily
      the experimental lineshapes, one has either to use unusual parameter values, or
      combine several simple motional modes. The multi-simple-mode reasoning assumes
      independence of the constituent modes, features ambiguity as different simple
      modes may be used, renders inter-system comparison difficult as the overall
      models differ, and makes possible model-improvement only by adding yet another
      simple mode, i.e., changing the overall model. 2H/MOMD/MAS is free of such
      limitations and inherently provides a clear physical interpretation. These
      features are illustrated. The advantage of 2H/MOMD/MAS in dealing with sensitive
      but hardly investigated slow-motional lineshapes is demonstrated by applying it
      to actual experimental data. The results differ from those obtained previously
      with a two-site exchange scheme that yielded unusual parameters.

PMID- 29208318
TI  - Liver resection is justified for patients with bilateral multiple colorectal
      liver metastases: A propensity-score-matched analysis.
AB  - BACKGROUND: Increasingly, patients with multiple colorectal liver metastases
      (CLM) are surgically treated. Some studies have shown that patients with bilobar
      and unilobar multiple CLM have similar outcomes, but other have shown that
      patients with bilobar CLM have worse outcomes after resection. We aimed to
      compare clinical outcomes of surgical treatment of bilobar and unilobar CLM using
      propensity score matching. METHODS: The single-institution study included
      patients who underwent hepatectomy for >=3 histologically confirmed CLM during
      1998-2014. Clinicopathologic characteristics and long-term outcomes were compared
      between patients with bilobar and unilobar CLM in a propensity-score-adjusted
      cohort. RESULTS: A total of 473 patients met the inclusion criteria, 271 (57%)
      with bilobar and 202 (43%) with unilobar CLM. In the propensity-score-matched
      population (bilobar, 170; unilobar, 170), no differences were observed according
      to the distribution of CLM except for a greater frequency of concomitant
      ablation, and R1 resection in the bilobar group. There was no difference between
      the bilobar and unilobar groups in 5-year overall survival rates (46% and 49%,
      respectively; P = 0.740) or 3-year recurrence-free survival rates (21% and 24%,
      respectively; P = 0.674). CONCLUSIONS: Tumor distribution may not affect the
      curability of surgery for multiple CLM. Liver resection would be justified for
      selected patients with bilobar CLM.

PMID- 29208319
TI  - Defining the incidence and clinical significance of lymph node metastasis in soft
      tissue sarcoma.
AB  - INTRODUCTION: The incidence and clinical significance of lymph node metastasis
      (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on
      extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with
      LNM at sarcoma diagnosis across all disease sites and histologies. METHODS: We
      identified and categorized 89,870 STS patients from the National Cancer Data Base
      (1998-2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in
      1404 patients; 1750 had clinically suspicious but not pathologically confirmed
      LNM (cN1). Survival analyses were performed by Kaplan-Meier method. RESULTS: Of
      3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous
      distant metastasis (M1). LNM affected a small proportion of patients (5.8%
      head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma
      (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the
      highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and
      leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0
      disease, median overall survival (OS) was 28.2 months, varying by histology.
      Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma,
      and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1,
      and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0
      months, p < 0.001). CONCLUSION: Despite clinical suspicion, pathologic LN
      evaluation in STS is inconsistently performed. LNM occurs across anatomic disease
      sites and is unevenly distributed across histologies. Although M1 disease
      portends poor prognosis regardless of LN status, LNM predicts worse OS in a
      histology-dependent manner in M0 disease.

PMID- 29208320
TI  - Efficacy of a massive transfusion protocol for hemorrhagic trauma resuscitation.
AB  - OBJECTIVES: New paradigm shifts in trauma resuscitation recommend that early
      reconstitution of whole blood ratios with massive transfusion protocols (MTP) may
      be associated with improved survival. We performed a preliminary study on the
      efficacy of MTP at an urban, Level 1 trauma center and its impact on
      resuscitation goals. METHODS: A case-control study was performed on consecutive
      critically-ill trauma patients over the course of 1 year. The trauma captain
      designated patients as either MTP activation (cases) or routine care without MTP
      (controls) in matched, non-randomized fashion. Primary outcomes were: time to
      initial transfusion; number of total units of packed red blood cells (pRBC) and
      fresh frozen plasma (FFP) transfused; and ratio of pRBC to fresh frozen plasma
      (pRBC:FFP). Secondary outcomes were in-hospital mortality, and length of stay.
      RESULTS: Out of 226 patients screened, we analyzed 58 patients meeting study
      criteria (32 MTP, 26 non-MTP). Study characteristics for the MTP and non-MTP
      groups were similar except age (34.0 vs. 45.85 years, p=0.015). MTP patients
      received blood products more expeditiously (41.7 minutes vs. 62.1 minutes,
      p=0.10), with more pRBC (5.19 vs 3.08 units, p=0.05), more FFP (0.19 vs 0.08
      units, p<0.01), and had larger pRBC:FFP ratios (1.90 vs 0.52, p<0.01). Secondary
      outcomes did not differ significantly but the MTP group was associated with a
      trend for decreased hospital length of stay (p=0.08). CONCLUSIONS: MTP resulted
      in clinically significant improvements in transfusion times and volumes. Further
      larger and randomized studies are warranted to validate these findings to
      optimize MTP protocols.

PMID- 29208321
TI  - Predicting 72-hour emergency department revisits: Methodological issues.

PMID- 29208322
TI  - Face mask leak with nasal cannula during noninvasive positive pressure
      ventilation: A randomized crossover trial.
AB  - BACKGROUND: Nasal cannula can achieve apneic oxygenation during emergency
      intubation. However, pre-procedure nasal cannula placement may be difficult in
      patients undergoing non-invasive positive pressure ventilation (NPPV) prior to
      intubation. Our objective was to compare mask leak during NPPV with versus
      without simultaneous application of nasal cannula. We hypothesized mask leak
      would be no worse with concomitant use of nasal cannula (non-inferiority design).
      METHODS: We performed a randomized crossover non-inferiority study of healthy
      volunteers. We randomized subjects undergoing 60s trials of NPPV (10cmH2O
      continuous positive airway pressure) to either NPPV alone (NPPV-a) or NPPV with
      nasal cannula at 15L/min (NPPV-nc). After a brief rest period, all subjects
      underwent the alternative intervention. The primary outcome was time averaged
      mask leak over 60s (L/min). We defined a non-inferiority margin of 5L/min.
      RESULTS: We enrolled 64 subjects. Mean time-averaged mask leak was 2.2L/min for
      NPPV-a versus 4.0L/min for NPPV-nc for a difference of 1.7L/min (one-sided 95% CI
      -infinity to 3.2L/min). NPPV-a resulted in higher mean minute volume received
      (13.5 versus 12.2L) and higher mean respiratory rates (14.8 versus 13.5 breaths
      per minute). CONCLUSION: The addition of nasal cannula during NPPV does not
      significantly increase mask leak. The simultaneous application of nasal cannula
      with NPPV may be a useful strategy to streamline airway management among patients
      undergoing NPPV prior to intubation.

PMID- 29208323
TI  - Evaluation of Posterior Cruciate Ligament and Intercondylar Notch in Subjects
      With Anterior Cruciate Ligament Tear: A Comparative Flexed-Knee 3D Magnetic
      Resonance Imaging Study.
AB  - PURPOSE: To determine if posterior cruciate ligament (PCL) and intercondylar
      notch (IN) morphometries and volumetrics act as risk factors for anterior
      cruciate ligament (ACL) tears. METHODS: A prospective case-controlled magnetic
      resonance imaging (MRI) study was conducted with subjects presenting noncontact
      knee injuries. Exclusion criteria were previous surgery, PCL tear,
      osteoarthritis, tumors, or infectious and inflammatory conditions. All
      participants underwent a flexed-knee 3-dimensional (3D) magnetic resonance
      imaging (MRI) to uniformly straighten PCL. MR images were independently reviewed
      by 2 radiologists and assessed for 2D and 3D measurements (bicondylar width; IN
      angle, depth, width, and cross-sectional area; PCL width, thickness, and cross
      sectional area; and IN and PCL volumes). Clinical profiles were tabulated and
      subjects were divided into cases (ACL tear) and controls (without ACL tear).
      RESULTS: The study was composed of 50 cases versus 52 controls (N = 102), with a
      mean age of 36.8 years. There was no difference between groups (P > .05)
      regarding age, gender, body mass index, time from injury, Tegner score, flexion
      angle, limb side, intensity of injury, or familial or opposite limb history of
      tear. Agreement between readers ranged from substantial to almost perfect.
      Subjects with ACL tear presented with lower IN width, lower IN minus PCL widths,
      lower Notch Width Index, higher PCL/IN width proportion, higher PCL thickness,
      lower IN depth minus PCL thickness, and higher PCL thickness/IN depth proportion
      (P < .05). Moreover, higher PCL/IN cross-sectional area proportion, higher PCL
      volumes (OR = 9.01), and higher PCL/IN volume proportion were also found in
      cases. CONCLUSIONS: Our study shows that subjects with ACL tears present not only
      reduced IN but also larger PCL dimensions. These findings, isolated and combined,
      and especially PCL volume, might be suggestive as risk factors for ACL tears
      owing to the reduction of its space inside the IN. LEVEL OF EVIDENCE: Level III,
      comparative group.

PMID- 29208324
TI  - Measuring the cost of a pediatric vaccine administration in the UK.
AB  - The administration of a vaccine dose involves a series of activities prior to and
      on the day of vaccine delivery. Total vaccination cost should include the cost of
      each activity, which is often not done or poorly reported. To calculate those
      costs a field study was performed in 6 United Kingdom (UK) sites (General
      Practitioner (GP) practices) during a 4-month period (April-June 2015). First, a
      workflow map of all the relevant vaccine-related activities per site was obtained
      through interviews. Second, time estimates for activities happening prior to the
      vaccination day were obtained through interviews and associated costs were
      calculated. A prospective, non-interventional study using Time & Motion (T&M)
      methodology was used to measure time for activities happening on the day of
      vaccination. Consumables, wastage, and guardian time were also collected. Third,
      the time for each task and for all tasks combined during the T&M study was
      analyzed using a random intercept model to account for site effect. Hundred and
      twenty-three T&M observations with approximately 20 per site were collected and
      were equally stratified by vaccination visit during the first year of a baby's
      life. Total cost per visit was L11.9 (site range: L8.6-L17.0) when supply cost
      and time for activities prior to the vaccination day were included. Time per dose
      administrated was 7.1 min (site range: 5.7-9.2) and the associated cost was L4.3
      (site range: L3.1-L6.2). The study demonstrates an accurate reflection of the
      time and cost involved in a vaccine dose administration in a pediatric setting in
      the UK. The amount measured is consistent with the current National Health
      Services fee schedule.

PMID- 29208325
TI  - Inhibitory effects of compound DMBT on hypoxia-induced vasculogenic mimicry in
      human breast cancer.
AB  - Breast cancer is one of the most serious malignant tumors that harm to women's
      health. Vasculogenic mimicry (VM) is an alternative type of blood supplement
      independent of endothelial vessels, which refers to the formation of tumor cell
      lined vessels and is associated with tumor invasion, metastasis and poor cancer
      patient prognosis. Prior antiangiogenic therapy just focused on vascular
      endothelial cells and did not significantly affect VM. DMBT, 6, 6'-bis (2, 3
      dimethoxybenzoyl)-a, a-D-trehalose, has shown to have multiple anti-tumor
      invasion and metastasis activities; however the exact mechanism is not thoroughly
      elucidated. In this study, we examined key molecular mechanisms underlying VM by
      using breast cancer cells MDA-MB-231 and MCF-7. We found that following the
      hypoxia treatment, the cells were easily to form VM networks and DMBT could
      inhibit VM formation of both MDA-MB-231 and MCF-7 cells in hypoxic condition.
      When tumor cells exposed to hypoxia environment, the expression of VM related
      proteins such as HIF-1alpha, VE-cadherin, MMP-9, Cdc42, and EGFR, p-Akt, p-mTOR
      were increased but decreased when exposed to hypoxia medium with DMBT. In MDA-MB
      231 cells, DMBT inhibit hypoxia-induced VM by suppress HIF-1alpha/VE
      cadherin/MMPs signaling pathway and in MCF-7 cells, DMBT had little effect on HIF
      1alpha or VE-cadherin but could inhibit cell autophagy to suppress VM formation.
      These results suggested that DMBT could serve as a therapeutic agent to inhibit
      VM formation in human breast cancer.

PMID- 29208326
TI  - A review on the antagonist Ebola: A prophylactic approach.
AB  - Ebola virus (EBOV), a member of Filoviridae virus family under the genus
      Ebolavirus, has emerged as a dangerous and potential threat to human health
      globally. It causes a severe and deadly hemorrhagic fever in humans and other
      mammals, called Ebola Virus Disease (EVD). In recent outbreaks of EVD, there has
      been loss of large numbers of individual's life. Therefore, EBOV has attracted
      researchers and increased interests in developing new models for virus evolution,
      and therapies. The EBOV interacts with the immune system of the host which led to
      understand how the virus functions and effects immune system behaviour. This
      article presents an exhaustive review on Ebola research which includes EVD
      illness, symptoms, transmission patterns, patho-physiology conditions,
      development of antiviral agents and vaccines, resilient health system, dynamics
      and mathematical model of EBOV, challenges and prospects for future studies.

PMID- 29208328
TI  - Different approaches for identifying important concepts in probabilistic
      biomedical text summarization.
AB  - Automatic text summarization tools help users in the biomedical domain to acquire
      their intended information from various textual resources more efficiently. Some
      of biomedical text summarization systems put the basis of their sentence
      selection approach on the frequency of concepts extracted from the input text.
      However, it seems that exploring other measures rather than the raw frequency for
      identifying valuable contents within an input document, or considering
      correlations existing between concepts, may be more useful for this type of
      summarization. In this paper, we describe a Bayesian summarization method for
      biomedical text documents. The Bayesian summarizer initially maps the input text
      to the Unified Medical Language System (UMLS) concepts; then it selects the
      important ones to be used as classification features. We introduce six different
      feature selection approaches to identify the most important concepts of the text
      and select the most informative contents according to the distribution of these
      concepts. We show that with the use of an appropriate feature selection approach,
      the Bayesian summarizer can improve the performance of biomedical summarization.
      Using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) toolkit, we
      perform extensive evaluations on a corpus of scientific papers in the biomedical
      domain. The results show that when the Bayesian summarizer utilizes the feature
      selection methods that do not use the raw frequency, it can outperform the
      biomedical summarizers that rely on the frequency of concepts, domain-independent
      and baseline methods.

PMID- 29208327
TI  - Botulinum toxin A for patients with orofacial dystonia: prospective,
      observational, single-centre study.
AB  - The objective of this study was to demonstrate the efficacy of intramuscular
      botulinum toxin type A (BTX-A) as a method of controlling the symptoms of focal
      facial dystonia. A prospective, longitudinal, observational, pre-post (case
      series) single-centre study was conducted over a period of 3 months, involving 30
      patients with focal dystonia. The patients were enrolled on a first-come, first
      served basis. For all patients, the abnormal movements were evaluated using the
      Abnormal Involuntary Movement Scale (AIMS). The AIMS results were recorded
      immediately before BTX-A injection (primary predictor variable) and after 3
      months (the toxin reaches its maximum effect 2 weeks after injection, and the
      effect is maintained for 3 months). An improvement in AIMS score was the primary
      outcome variable. Treatment efficacy was evaluated using the Pearson correlation
      index with a level of significance of P<0.05. The average age of the study
      subjects was 70.9+/-12.7years (20 female, 10 male). The mean dose of BTX-A used
      was 27.4+/-20.5U. The mean improvement in AIMS score after treatment was 5.2+/
      4.2. A significant correlation was found between the dose applied and the
      reduction in AIMS score (P<0.05). BTX-A can be used in the treatment of focal
      dystonia and provides reproducible results.

PMID- 29208329
TI  - The Effects of Body Mass Index on Pain Control With Liposomal Bupivacaine in Hip
      and Knee Arthroplasty.
AB  - BACKGROUND: There is evidence to suggest that liposomal bupivacaine (LB) is an
      effective component of a multimodal pain regimen for total joint arthroplasty
      (TJA). Obesity has been associated with chronic pain following TJA. This study
      assessed whether early postoperative pain is affected by body mass index (BMI),
      and whether the standard LB dose has similar effects on obese vs nonobese
      patients. METHODS: A retrospective analysis of 2629 primary TJA over a 12-month
      period was conducted, with LB used in half of this group. Patients were further
      classified as nonobese (BMI < 30) or obese (BMI >= 30). Pain scores and narcotic
      use were recorded. Independent-sample t-tests were used for continuous variables
      and chi-squared analyses for categorical variables. A multivariate regression
      analysis was performed. RESULTS: Significantly less narcotic was required on
      postoperative days (POD) 0 and 1 in patients receiving LB compared to those who
      did not in both obese and nonobese patient groups. On POD 2, obese and nonobese
      patients had an increase in narcotic requirement, which was significant in obese
      patients. A regression analysis found that on POD 0 and POD 1, lack of LB use,
      obesity, and younger age were independently associated with increased narcotic
      use. CONCLUSION: While narcotic requirement of obese and nonobese patients
      decreased on POD 0 and POD 1 with initiation of LB at our institution, all
      patients demonstrated increased narcotic requirement on POD 2 which was
      statistically and clinically significant in obese patients. Further studies are
      needed to determine the optimal pain regimen in the growing obese population
      undergoing TJA.

PMID- 29208330
TI  - What Is the Impact of Advancing Age on the Outcomes of Total Hip Arthroplasty?
AB  - BACKGROUND: The global demand for total hip arthroplasty (THA) is increasing,
      underscoring its moniker as the "operation of the century." However, debate still
      exists as to whether the elderly who undergo the operation achieve the same
      outcomes as those younger. In this study, we sought to investigate the
      association between older age and the risks and benefits of THA. METHODS: In this
      study, we aimed to compare the risks and benefits of THA of those aged >=80 years
      vs those <80 years. We analyzed the physical status component of the Short-Form
      12 Health Survey, complications within 12 months, all-cause mortality, length of
      hospital stay (LOS), and discharge to rehabilitation in 2457 cases of primary THA
      using multivariate modeling. RESULTS: There was no difference in improvement of
      those older vs the younger group in physical functioning. However, the older
      group had 2.87 times greater odds of experiencing a post-operative medical
      complication and 3.49 times the rate of all-cause mortality (P < .001).
      Additionally, the older group encountered an additional median 0.21-day increase
      in LOS and had 3.93 times greater odds of being discharged to rehabilitation
      rather than home (P < .001). We were unable to demonstrate any difference between
      groups in terms of post-operative surgical or wound-related complications.
      CONCLUSION: The elderly stand to gain equivalent benefits from THA as those
      younger in terms of physical functioning. However, this benefit needs to be
      balanced against the increased risk of post-operative medical complications,
      increased LOS, increased requirement for rehabilitation, and ultimately the
      increased risk of mortality.

PMID- 29208331
TI  - Autoimmune and medication-induced lymphadenopathies.
AB  - This article will provide a discussion of some common autoimmune disorders that
      could affect the lymph nodes and potentially mimic B and T-cell lymphomas. Some
      of these disorders are more characteristic of individuals in the pediatric age
      group (autoimmune lymphoproliferative syndrome, Kawasaki disease), while others
      present in older individuals (rheumatoid arthritis, lupus erythematosus,
      sarcoidosis). A common finding that groups all of these disorders together is the
      overall relative preservation of the architecture, a feature that can be
      particularly helpful to distinguish them from many B and T-cell lymphomas.
      Another area of interest, that will be discussed in this review, is the
      pathologic manifestations that can be present in lymph nodes secondary to
      medications. Such alterations range from 'reactive' forms of follicular,
      interfollicular or paracortical hyperplasia, to specific B and T-cell
      lymphoproliferative disorders (particularly documented in association with
      methotrexate and TNF-inhibitors).

PMID- 29208332
TI  - Severe aortic arch calcification predicts mortality in patients undergoing
      peritoneal dialysis: Response to methodological issues.

PMID- 29208333
TI  - The role of corticosteroid in septic shock patients: The authors reply.

PMID- 29208334
TI  - Factors influencing recurrent emergency department visits for epistaxis in the
      elderly.
AB  - OBJECTIVE: Our objective is to determine the risk factors associated with
      recurrent epistaxis requiring emergency department (ED) visits in the elderly.
      METHODS: We used a 5% national sample of Medicare data from January 2012 through
      December 2013. Our cohort included patients with a new diagnosis of epistaxis in
      the ED, defined as no epistaxis in the prior 12 months. We assessed the rates of
      ED visits for recurrent epistaxis in the 12 months following the incident visit.
      Our variables included demographics, geographic location, procedures performed
      during the incident visit and comorbidities. RESULTS: Out of the 4120 patients
      with incident epistaxis, 775 were readmitted with recurrent epistaxis within 12
      months. 60% presented in the first 30days and 75% within 90 days. There was a
      significant increase in ED visits for patients over 75 years of age and in men
      compared to women. Recurrent ED visits for epistaxis was higher in patients with
      congestive heart failure, diabetes mellitus, and obstructive sleep apnea compared
      to those without these comorbidities. CONCLUSION: Additional ED visits for
      epistaxis are more common in the elderly and in males. Congestive heart failure,
      diabetes mellitus and obstructive sleep apnea were found to be independent risk
      factors.

PMID- 29208335
TI  - Fructose consumption and its impact on human health: Diet and risk of
      cardiovascular disease.

PMID- 29208337
TI  - "The Pink Cloud": Can Technology Curb Addiction.

PMID- 29208336
TI  - A framework for testing and comparing binaural models.
AB  - Auditory research has a rich history of combining experimental evidence with
      computational simulations of auditory processing in order to deepen our
      theoretical understanding of how sound is processed in the ears and in the brain.
      Despite significant progress in the amount of detail and breadth covered by
      auditory models, for many components of the auditory pathway there are still
      different model approaches that are often not equivalent but rather in conflict
      with each other. Similarly, some experimental studies yield conflicting results
      which has led to controversies. This can be best resolved by a systematic
      comparison of multiple experimental data sets and model approaches. Binaural
      processing is a prominent example of how the development of quantitative theories
      can advance our understanding of the phenomena, but there remain several
      unresolved questions for which competing model approaches exist. This article
      discusses a number of current unresolved or disputed issues in binaural
      modelling, as well as some of the significant challenges in comparing binaural
      models with each other and with the experimental data. We introduce an auditory
      model framework, which we believe can become a useful infrastructure for
      resolving some of the current controversies. It operates models over the same
      paradigms that are used experimentally. The core of the proposed framework is an
      interface that connects three components irrespective of their underlying
      programming language: The experiment software, an auditory pathway model, and
      task-dependent decision stages called artificial observers that provide the same
      output format as the test subject.

PMID- 29208338
TI  - Risky Behaviors of Mothers with Infants on Sudden Infant Death Syndrome in
      Turkey.
AB  - PURPOSE: Sudden infant death syndrome is the most common cause of death during
      the post-neonatal period. Factors such as sleeping position, bed sharing, pillow
      use, smoking during pregnancy and the breastfeeding period constitute risk
      factors for sudden infant death syndrome. This study aims to identify the risky
      behaviors of mothers with infants that may put their children at risk for sudden
      infant death syndrome. DESIGN AND METHODS: This is a cross-sectional, descriptive
      study. Data were collected using a questionnaire that was developed by the
      researchers. The questionnaire was filled out by 456 mothers who applied to the
      family health center between October 2014 and January 2015. RESULTS: The greatest
      risk factor is the infant's sleeping position. A total of 77.9% of the mothers
      put their babies in bed in a non-supine position; 65.8% used a pillow when they
      put their babies in bed, 52.9% used a soft mattress, and 28.5% shared their beds
      with their babies. Prone sleeping was more likely to occur when smoke was present
      in the home or a pillow was used. CONCLUSION: Nurses should notify families of
      the risky behaviors that can cause sudden infant death syndrome and plan
      appropriate nursing care.

PMID- 29208339
TI  - Comment on "Indoor terrestrial gamma dose rate mapping in France: A case study
      using two different geostatistical models" by Warnery et al. (J. Environ.
      Radioact. 2015, 139, 140-148).

PMID- 29208340
TI  - Different indicators for postprocedural mitral stenosis caused by single- or
      multiple-clip implantation after percutaneous mitral valve repair.
AB  - BACKGROUND: Postprocedural mitral stenosis (MS) is a main limitation for
      MitraClipTM (Abbot Vascular, Inc., Santa Clara, CA, USA) procedure. The purpose
      of this study was to detect the preprocedural predictors of high transmitral
      pressure gradient (TMPG) after MitraClipTM implantation, which indicated
      postprocedural mitral stenosis (MS). METHODS: We studied 79 patients who were
      implanted with MitraClipTM in our institute. Before the procedure, mitral valve
      orifice area (MVOA), and anterior-posterior (AP) and medial-lateral (ML) mitral
      annular diameters were measured at diastole using three-dimensional (3D)
      transesophageal echocardiography (TEE) data set. After the procedure, the mean
      TMPG was assessed using continuous-wave (CW) Doppler by periprocedural TEE.
      RESULTS: Preprocedural MVOA, and AP and ML diameter of left ventricular (LV)
      inflow orifices were larger in patients with mean TMPG <=4mmHg than in patients
      with TMPG >4mmHg after 1-and 2-clip implantation. The large MVOA and ML diameter
      of LV inflow orifice strongly correlated with the low TMPG after 1- and 2-clip
      implantation. As a result of the receiver operating characteristic curve
      analysis, the preprocedural MVOA predicted the low postprocedural TMPG more
      accurately than the ML diameter of LV inflow orifice after 1-clip implantation
      either in the degenerative or functional mitral regurgitation (MR) patients.
      After 2-clip implantation, however, the preprocedural ML diameter of LV inflow
      orifice predicted it more accurately than the MVOA in the degenerative and
      functional MR patients. CONCLUSIONS: 3D TEE derived MVOA predicts the
      postprocedural MS after 1-clip implantation, however, preprocedural ML diameter
      of LV inflow orifice is more useful to predict after 2-clip implantation.

PMID- 29208341
TI  - Hemodynamic correlates of nutritional indexes in heart failure.
AB  - BACKGROUND: Malnutrition in heart failure (HF) is related to altered intestinal
      function, which could be due to hemodynamic changes. We investigated the
      usefulness of novel nutritional indexes in relation to hemodynamic parameters.
      METHODS: We retrospectively analyzed 139 HF patients with reduced ejection
      fraction who underwent right heart catheterization. We investigated correlations
      between right side pressures and nutritional indexes, which include controlling
      nutritional (CONUT) score and geriatric nutritional risk index (GNRI). Receiver
      operating characteristic (ROC) curves were generated to investigate the
      prognostic accuracy of CONUT score and GNRI for a composite of death or HF
      hospitalization in 12 months. Logistic regression analysis was performed to
      investigate whether hemodynamic correlates were associated with malnutrition,
      which was defined based on CONUT sore or GNRI. RESULTS: Higher right side
      pressures were positively correlated with worse nutritional status according to
      CONUT score, but were negatively correlated with worse nutritional status
      according to GNRI. Area under ROC curve for the composite endpoint was 0.746 in
      CONUT score and 0.576 in GNRI. The composite endpoint occurred in 40% of CONUT
      score>=3 and in 11% of CONUT score<3 (p<0.001). These relationships were also
      investigated with GNRI (40% of GNRI<95 vs. 17% of GNRI>=95, p=0.002). In
      multivariate analysis, higher right atrial pressure was significantly associated
      with higher CONUT score, while no hemodynamic parameter was related to GNRI.
      CONCLUSIONS: CONUT score was associated with right side congestion, while no
      association between GNRI and right side congestion was noted. CONUT score had
      better predictive value than GNRI.

PMID- 29208342
TI  - Pediatric stroke related to Lyme neuroborreliosis: Data from the Swiss
      NeuroPaediatric Stroke Registry and literature review.
AB  - BACKGROUND: Cerebrovascular complications of Lyme neuroborreliosis (LNB) are
      poorly documented in the paediatric population. METHODS: We performed a
      retrospective analysis from prospectively registered cases of acute ischemic
      stroke (AIS) from the Swiss NeuroPaediatric Stroke Registry (SNPSR) from 2000 to
      2015. Only cases with serologically confirmed LNB were included. In addition, a
      literature review on paediatric stroke cases secondary to Lyme neuroborreliosis
      in the same time frame was performed. RESULTS: 4 children out of 229 children
      with arterial ischemic childhood stroke and serologically confirmed LNB were
      identified in the SNPSR giving a global incidence of 1.7%. Median age was 9.9
      years. A prior history of tick bites or erythema migrans (EM) was reported in two
      cases. Clinical presenting signs were suggestive of acute cerebellar/brainstem
      dysfunction. On imaging, three children demonstrated a stroke in the distribution
      of the posterior inferior cerebellar artery. The remaining fourth child had a
      "stroke-like" picture with scattered white matter lesions and a multifocal
      vasculitis with prominent basilar artery involvement. Lymphocytic pleocytosis as
      well as intrathecal synthesis of Borrelia burgdorferi antibodies were typical
      biological features. Acute intravenous third generation cephalosporins proved to
      be effective with rapid improvement in all patients. No child had recurrent
      stroke. Data from the literature concerning eight patients gave similar results,
      with prominent posterior circulation stroke, multifocal vasculitis and abnormal
      CSF as distinctive features. CONCLUSIONS: Lyme Neuroborreliosis accounts for a
      small proportion of paediatric stroke even in an endemic country. The strong
      predilection towards posterior cerebral circulation with clinical occurrence of
      brainstem signs associated with meningeal symptoms and CSF lymphocytosis are
      suggestive features that should rapidly point to the diagnosis. This can be
      confirmed by appropriate serological testing in the serum and CSF. Clinicians
      must be aware of this rare neurological complication of Lyme disease that demands
      specific antibiotic treatment.

PMID- 29208343
TI  - Single-center experience with intrathecal administration of Nusinersen in
      children with spinal muscular atrophy type 1.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disorder mainly
      characterized by proximal muscle weakness. There have been enormous advances in
      therapeutic development with the possibility to influence the clinical course of
      the disease. Nusinersen is the first approved drug to treat SMA. It is
      administered intrathecally and acts as splicing modifier of the SMN2 gene.
      METHODS: Lumbar punctures were performed using a standardized protocol. To
      evaluate safety and feasibility of the intrathecal treatment, vital signs and the
      need for sedation, analgesia or mechanical ventilation during the procedure were
      monitored. Furthermore, the number of puncture attempts, the injection site and
      the macroscopic appearance of cerebrospinal fluid were documented. RESULTS:
      Treatment with Nusinersen was initiated in 20 children aged from 2 to 50 months.
      Administration of a local anesthetic cream on the puncture site and a peripheral
      analgesic led to an adequate pain management. We observed a beneficial
      distraction through the possibility to watch a movie or listen to music during
      the procedure. In some cases, an additional sedation was necessary. In patients
      accustomed to non-invasive ventilation, this was used during lumbar punctures. On
      average, 1.5 +/- 1.0 puncture attempts were performed between L 4/5 and L 2/3. If
      required, the position of the medullary cone was identified by ultrasound to
      guarantee a safe puncture above L 3/4. CONCLUSIONS: Lumbar punctures for
      intrathecal administration of Nusinersen could be performed without any relevant
      complications. With the described approach lumbar punctures were tolerated well
      in all investigated age groups.

PMID- 29208344
TI  - Characteristic diversity and antimicrobial resistance of Salmonella from
      gastroenteritis.
AB  - Salmonella is a leading cause of foodborne disease worldwide and may cause to
      gastroenteritis. The aim of this study was to determine the prevalence,
      serotypes, virulence genes, molecular subtyping, and antibiotic resistance
      phenotype of Salmonella from gastroenteritis in Hubei, China. Of 500 patients
      stools samples collected from January 2015 to January 2016, 52 (10.40%) samples
      were contaminated by Salmonella. The results showed that most of the isolates
      were positive for eight virulence genes that appear on pathogenicity islands,
      prophages, plasmid, and fimbrial. A total of twelve serotypes were found.
      Antimicrobial susceptibility results indicated that most strains were resistant
      to ampicillin (57.69%), kanamycin (53.85%), and tetracycline (40.38%). There were
      33 STs on MLST types, and were grouped into two clusters. Thus, our findings
      provided insights into the dissemination of antibiotic resistant strains, genetic
      diversity, and improved our knowledge of microbiological risk assessment in
      Salmonella from gastroenteritis.

PMID- 29208345
TI  - Multi-class parkinsonian disorders classification with quantitative MR markers
      and graph-based features using support vector machines.
AB  - BACKGROUND AND PURPOSE: In this study we attempt to automatically classify
      individual patients with different parkinsonian disorders, making use of pattern
      recognition techniques to distinguish among several forms of parkinsonisms (multi
      class classification), based on a set of binary classifiers that discriminate
      each disorder from all others. METHODS: We combine diffusion tensor imaging,
      proton spectroscopy and morphometric-volumetric data to obtain MR quantitative
      markers, which are provided to support vector machines with the aim of
      recognizing the different parkinsonian disorders. Feature selection is used to
      find the most important features for classification. We also exploit a graph
      based technique on the set of quantitative markers to extract additional features
      from the dataset, and increase classification accuracy. RESULTS: When graph-based
      features are not used, the MR markers that are most frequently automatically
      extracted by the feature selection procedure reflect alterations in brain regions
      that are also usually considered to discriminate parkinsonisms in routine
      clinical practice. Graph-derived features typically increase the diagnostic
      accuracy, and reduce the number of features required. CONCLUSIONS: The results
      obtained in the work demonstrate that support vector machines applied to
      multimodal brain MR imaging and using graph-based features represent a novel and
      highly accurate approach to discriminate parkinsonisms, and a useful tool to
      assist the diagnosis.

PMID- 29208346
TI  - Advancing the GI frontier for patients with CF.

PMID- 29208347
TI  - Usefulness of bandage contact lenses in the immediate postoperative period after
      uneventful myopic LASIK.
AB  - PURPOSE: To determine the usefulness of a silicone-hydrogel bandage contact lens
      (BCL) in the immediate postoperative period after uneventful myopic laser in-situ
      keratomileusis (LASIK). METHODS: The study design was randomized but not masked
      and data collection was prospective. This study comprised 51 consecutive myopic
      eyes intervened by means of the LASIK technique to compensate their refractive
      error. Patients were randomly assigned to two different groups. The experimental
      group included 24 eyes of 12 patients that were fitted with a BCL immediately
      after the flap replacement. The control group included 27 eyes of 14 patients
      with no BCL. Patients were examined 24h after the surgery; the experimental group
      was analyzed immediately after the extraction of the BCL. Postoperative
      uncorrected distance visual acuity (UDVA) and postoperative topographic indexes
      were compared to baseline in both groups. RESULTS: The experimental group
      achieved worse results in the majority of the studied variables. Postoperative
      UDVA was worse in experimental group (p<0.01). Likewise, corneal asphericity (Q)
      was significantly higher in experimental group (p=0.024). Topographic indexes
      showed higher asymmetry in the corneal maps pertaining to experimental group.
      Specifically, the index of surface variance (ISV) (p=0.017) and index of vertical
      asymmetry (IVA) (p=0.031) were higher in experimental group. Also, the
      postoperative central corneal thickness (CCT) resulted in higher values for eyes
      pertaining to experimental group. CONCLUSIONS: The fitting of a silicone-hydrogel
      BCL after uneventful LASIK provokes morphological changes in the ocular
      structures that may lead to a worse UDVA secondary to a higher postoperative CCT
      and corneal edema.

PMID- 29208348
TI  - Nuclear migration in mammalian brain development.
AB  - During development of the mammalian brain, neural stem cells divide and give rise
      to adult stem cells, glia and neurons, which migrate to their final locations.
      Nuclear migration is an important feature of neural stem cell (radial glia
      progenitor) proliferation and subsequent postmitotic neuronal migration. Defects
      in nuclear migration contribute to severe neurodevelopmental disorders such as
      microcephaly and lissencephaly. In this review, we address the cellular and
      molecular mechanisms responsible for nuclear migration during the radial glia
      cell cycle and postmitotic neuronal migration, with a particular focus on the
      role of molecular motors and cytoskeleton dynamics in regulating nuclear
      behavior.

PMID- 29208349
TI  - Re: "Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical
      Practice Guidelines of the European Society for Vascular Surgery (ESVS)".

PMID- 29208351
TI  - Detection radius of EMG for fasciculations: Empiric study combining
      ultrasonography and electromyography.
AB  - OBJECTIVE: The aims of this study were to investigate the detection radius and
      sensitivity of EMG for fasciculations. METHODS: Muscle ultrasonography was
      performed simultaneously to EMG recordings in patients with fasciculations in the
      context of amyotrophic lateral sclerosis. Ultrasonography and EMG parameters were
      analyzed for selected fasciculations. RESULTS: A total of 381 fasciculations were
      detected by ultrasonography in 18 muscles of 10 patients. Out of these, 125 (33%)
      were EMG-negative. In contrast, none of the fasciculations detected by EMG were
      ultrasonography-negative. EMG detection probability decreased significantly with
      increasing distance from the center of the fasciculation. EMG detection rate was
      98% when the EMG needle was located within the fasciculation and 50% at 7.75 mm
      distance from the fasciculation center. In addition, EMG detection depended
      significantly on cross-sectional area of the fasciculation and presence of
      neurogenic changes. CONCLUSIONS: For detecting the same fasciculations, EMG is
      less sensitive than ultrasonography. EMG detection probability decreases sharply
      at a distance comparable to motor unit size. SIGNIFICANCE: These results extend
      previous knowledge about superior sensitivity of ultrasonography for
      fasciculations. Moreover, our novel bimodal detection method provides first in
      vivo data about the EMG detection radius for fasciculations in a clinical
      setting.

PMID- 29208350
TI  - Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial
      Cells in Vitro.
AB  - OBJECTIVE: Endothelial cells (ECs) play an important role in neovascularisation,
      but are too limited in number for adequate therapeutic applications. Mesenchymal
      stem cells (MSCs) have the potential to differentiate into endothelial lineage
      cells, which makes them attractive candidates for therapeutic angiogenesis. The
      aim of this study was to investigate efficient differentiation of MSCs into ECs
      by inducing medium in vitro. METHODS: MSCs were isolated from bone marrow by
      density gradient centrifugation. The characterisation of the MSCs was determined
      by their cluster of differentiation (CD) marker profile. Inducing medium
      containing vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), insulin like growth factor (IGF), epidermal growth factor (EGF),
      ascorbic acid, and heparin was applied to differentiate the MSCs into ECs.
      Endothelial differentiation was quantitatively evaluated using flow cytometry.
      Real time quantitative PCR (qRT-PCR) was used to analyse mRNA expression of
      endothelial markers. Tube formation assay was further performed to examine the
      functional status of the differentiated MSCs. RESULTS: Flow cytometry analysis
      demonstrated that CD31+ and CD34+ cells increased steadily from 12% at 3 days, to
      40% at 7 days, and to 60% at 14 days. Immunofluorescence staining further
      confirmed the expression of CD31 and CD34. qRT-PCR showed that expression of von
      Willebrand factor (vWF), vascular endothelial cadherin (VE-cadherin) and vascular
      endothelial growth factor receptor-2 (VEGFR-2) were significantly higher in the
      induced MSCs group compared with the uninduced MSCs group. The functional
      behavior of the differentiated cells was tested by tube formation assay in vitro
      on matrigel. Induced MSCs were capable of developing capillary networks, and
      progressive formation of vessel like structures was associated with increased EC
      population. CONCLUSIONS: These results provide a method to efficiently promote
      differentiation of MSCs into ECs in vitro for potential application in the
      treatment of peripheral arterial disease.

PMID- 29208352
TI  - Multicentre study of the impact of factors that may affect long-term survival
      following pancreaticoduodenectomy for distal cholangiocarcinoma.
AB  - BACKGROUND: Although the peri-operative mortality following
      pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased,
      the post-operative morbidity remains high. The aim of this study was to evaluate
      the impact of factors that may affect the long term survival for patients with
      DCC following PD. METHODS: All patients who underwent PD for DCC between January
      2000 and December 2015 in 5 tertiary referral centers underwent retrospective
      medical record review. Factors likely to influence overall (OS) and disease-free
      (DFS) survivals were assessed by univariate and multivariate analysis. RESULTS: A
      total of 201 on 217 patients who underwent PD for DCC were included for further
      analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and
      5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The
      median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of
      60%, 37% and 28%. Following multivariate analysis, peri-operative blood
      transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003)
      and DFS (HR = 2.08 [1.24-3.5], P = 0.005). CONCLUSION: This study confirms the
      negative impact of PBT on the oncologic result following PD for DCC.

PMID- 29208353
TI  - AtMMS21: Connecting DNA Repair and Root Development.
AB  - Two recent reports show that SUMO ligase AtMMS21 controls the cell cycle through
      dissociating the E2Fa/DPa complex, and regulates chromatin remodeling by
      maintaining the stability of BRAHMA. We discuss these novel functions of AtMMS21
      and its potential role in linking DNA repair and root development.

PMID- 29208355
TI  - Usage of Prophylactic Cranial Irradiation in Elderly Patients With Small-cell
      Lung Cancer.
AB  - BACKGROUND: Prophylactic cranial irradiation (PCI) reduces the risk of overt
      brain metastases in patients with small-cell lung cancer (SCLC) and is currently
      recommended in guidelines for both limited and extensive disease. Given the
      concerns about the greater frequency of neurologic side effects in elderly
      patients, we studied the association among age, PCI usage, and survival for SCLC
      patients in the Netherlands. PATIENTS AND METHODS: Data from the Netherlands
      Cancer Registry for patients diagnosed with SCLC from 2009 to 2013 were queried.
      Separate analyses were performed for patients with stage I to III, treated with
      chemoradiotherapy (n = 1684) and patients with stage IV, treated with
      chemotherapy or chemoradiotherapy (n = 3481). Patients with brain metastasis at
      diagnosis were excluded. RESULTS: For patients with stage I to III, the overall
      PCI usage rate was 74%, and the rate decreased with age, from 78% for patients
      aged 18 to 59 years to 66% for patients aged >= 80 years. For patients with stage
      IV, the overall PCI usage rate was 41% and decreased with age, from 46% for
      patients aged 18 to 59 years to 23% for patients aged >= 80 years. Gender and
      socioeconomic status did not affect the PCI rates. For patients aged < 70 years
      and treated with PCI, the median survival was 45, 24, and 12 months for stage I
      and II, III, and IV, respectively. For patients aged >= 70 years treated with
      PCI, the corresponding survival duration was 33, 17, and 10 months. CONCLUSION:
      In the Dutch population, PCI usage rates were fairly high but were significantly
      lower for elderly patients.

PMID- 29208354
TI  - More Than a "Number": Perspectives of Prenatal Care Quality from Mothers of Color
      and Providers.
AB  - INTRODUCTION: African American mothers and other mothers of historically
      underserved populations consistently have higher rates of adverse birth outcomes
      than White mothers. Increasing prenatal care use among these mothers may reduce
      these disparities. Most prenatal care research focuses on prenatal care adequacy
      rather than concepts of quality. Even less research examines the dual
      perspectives of African American mothers and prenatal care providers. In this
      qualitative study, we compared perceptions of prenatal care quality between
      African American and mixed race mothers and prenatal care providers. METHODS:
      Prenatal care providers (n = 20) and mothers who recently gave birth (n = 19)
      completed semistructured interviews. Using a thematic analysis approach and
      Donabedian's conceptual model of health care quality, interviews were analyzed to
      identify key themes and summarize differences in perspectives between providers
      and mothers. FINDINGS: Mothers and providers valued the tailoring of care based
      on individual needs and functional patient-provider relationships as key elements
      of prenatal care quality. Providers acknowledged the need for knowing the social
      context of patients, but mothers and providers differed in perspectives of
      "culturally sensitive" prenatal care. Although most mothers had positive prenatal
      care experiences, mothers also recalled multiple complications with providers'
      negative assumptions and disregard for mothers' options in care. CONCLUSIONS:
      Exploring strategies to strengthen patient-provider interactions and
      communication during prenatal care visits remains critical to address for
      facilitating continuity of care for mothers of color. These findings warrant
      further investigation of dual patient and provider perspectives of culturally
      sensitive prenatal care to address the service needs of African American and
      mixed race mothers.

PMID- 29208356
TI  - Practice Patterns and Outcomes in Elderly Stage I Non-Small-cell Lung Cancer: A
      2004 to 2012 SEER Analysis.
AB  - BACKGROUND: We reviewed the population-based treatment patterns and outcomes for
      elderly patients with stage I non-small-cell lung cancer (NSCLC) treated from
      2004 to 2012. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End
      Results (SEER) database, we identified biopsy-proven stage I NSCLC cases
      diagnosed from 2004 to 2012. The patients were divided into 5-year age subsets
      (60-64, 65-69, 70-74, 75-79, 80-84, 85-89, and >= 90 years). The demographic
      data, therapy, and survival were compared by year. Trends in overall survival
      (OS), cancer-specific survival (CSS), and practice patterns were analyzed.
      RESULTS: A total of 62,213 cases were identified. The use of surgery declined
      sharply with age. Patients aged 60 to 64 years had a surgical rate of 81%
      compared with 21% for those aged >= 90 years (P < .0001). Radiation use increased
      (from 11% to 39%; P < .0001), as did the receipt of neither surgery nor radiation
      (from 7% to 40%; P < .0001). When analyzing the annual trends, radiation use
      increased, with fewer patients forgoing treatment from 2004 to 2012 (P < .0001).
      From 2004 to 2011, CSS at 2 years improved significantly for patients treated
      with radiation alone (from 48% to 72%; P < .0001) and more subtly for those
      receiving surgery alone (from 87% to 91%; P < .0001). The outcomes were stable
      for those receiving neither surgery nor radiation (38% to 45%; P = NS). Surgical
      outcomes declined with advancing age (P < .0001); however, the radiation outcomes
      did not (P = NS). CONCLUSION: With advancing age, radiation replaces surgery as
      the most used treatment for early-stage NSCLC. OS and CSS have improved
      significantly for elderly stage I NSCLC patients treated with radiation alone
      during a timeline concurrent with the widespread adoption of stereotactic body
      radiation therapy. Dedicated prospective studies are indicated, because these
      findings are limited by the inherent biases of using the SEER database alone.

PMID- 29208357
TI  - Differential expression of IGFBPs in Laron syndrome-derived lymphoblastoid cell
      lines: Potential correlation with reduced cancer incidence.
AB  - Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is a growth
      disorder that results from mutation of the GH-receptor (GHR) gene leading to
      congenital insulin-like growth factor-1 (IGF-1) deficiency. Recent
      epidemiological studies have shown that LS patients are protected from cancer
      development. Genome-wide profiling identified genes and signaling pathways that
      are differentially represented in LS patients, and that may contribute to cancer
      protection. The present study was aimed at evaluating the hypothesis that IGF
      binding proteins (IGFBPs) are differentially expressed in LS, most probably as a
      result of low circulating levels of IGF-1. Furthermore, we postulated that IGFBPs
      might be differentially regulated by oxidative stress in this condition and,
      therefore, may contribute to cancer evasion. Our results show that IGFBP-3, which
      is predominantly protective, was highly expressed in LS-derived lymphoblastoid
      cells in comparison to control cells from the same ethnic group. On the other
      hand, levels of IGFBP-2, -4, -5, and -6 were diminished in LS patients, as
      demonstrated by RQ-PCR, Western immunoblots and confocal immunofluorescence. In
      addition, our data provide evidence for a pattern of IGFBP response to H2O2
      treatment that might be associated with distinct expression of apoptosis markers
      (BCL2, pro-caspase-9, pro-caspase-3) in LS. In summary, differential expression
      of specific IGFBPs in LS might be correlated with cellular mechanisms underlying
      cancer protection and, probably, additional phenotypes due to congenital IGF-1
      deficiency.

PMID- 29208358
TI  - Effect of (-)-epicatechin, a flavonoid on the NO and NOS activity of Raillietina
      echinobothrida.
AB  - (-)-Epicatechin, a natural flavonoid reportedly has huge pharmacological
      properties. In this study the cestocide effect of (-)-epicatechin is demonstrated
      in Raillietina echinobothrida. Although the antiparasitic activity of (-)
      epicatechin has been demonstrated against protozoa, helminths and ectoparasites,
      in the present study the cestocide activity of (-)-epicatechin is shown to be
      related to a decrease in nitric oxide synthase (NOS) activity and nitric oxide
      (NO) production. On exposure to 0.53mg/ml each of epicatechin, reference drug
      praziquantel and O Nitro-l- Arginine Methyl Ester (NOS inhibitor), the parasites
      attained paralysis at 10.15, 0.27 and 11.21h followed by death at 30.15, 1.21 and
      35.18h respectively. Biochemical analysis showed a significant decrease in
      activity of NOS (57.360, 36.040 and 44.615%) and NO (41.579, 19.078 and 24.826%)
      in comparison to the controls. NADPH-diaphorase histochemical staining (a
      selective marker for NOS in neuronal tissue) demonstrated a pronounced decline in
      the visible staining activity in the tegument, subtegument and the peripheral
      nerve regions following exposure to the treatments. Strong binding affinity of (
      )-epicatechin with NOS protein was also revealed through docking studies. The
      results strongly define the probable anthelmintic activity of our compound
      through its influence on the NOS activity.

PMID- 29208359
TI  - Aminoguanidine hydrazones (AGH's) as modulators of norfloxacin resistance in
      Staphylococcus aureus that overexpress NorA efflux pump.
AB  - One of the promising fields for improving the effectiveness of antimicrobial
      agents is their combination with efflux pump inhibitors (EPIs), which besides
      expanding the use of existing antibiotics. The goal of this research was to
      evaluate a series of aminoguanidine hydrazones (AGH's, 1-19) as antibacterial
      agents and NorA efflux pump inhibitors in Staphylococcus aureus strain SA-1199B.
      Molecular modeling and docking studies were also performed in order to explain at
      the molecular level the interactions of the compounds with the generated NorA
      efflux pump model. The MICs of the antibiotic and ethidium bromide were
      determined by microdilution assay in absence or presence of a subinhibitory
      concentration of aminoguanidine hydrazones and macrophages viability was
      determined through MTT assay. Bioinformatic software Swiss-Model and AutoDock 4.2
      were used to perform modeling and docking studies, respectively. As results, all
      AGH's were able to potentiate the action for the antibiotic norfloxacin, causing
      MIC's reduction of 16-fold and 32-fold to ethidium bromide. In the cell viability
      test, the concentration of 10 MUg/mL showed better results than 90% and the
      concentration of 1000 MUg/mL showed the lowest viability, reaching a maximum of
      50% for the analyzed aminoguanidine hydrazones. Molecular docking studies showed
      that both norfloxacin and derivative 13 were recognized by the same binding site
      of NorA pump, suggesting a competitive mechanism. The present work demonstrated
      for the first time that AGH derivatives have potential to be putative inhibitors
      of NorA efflux pump, showing a promising activity as an antibacterial drug
      development.

PMID- 29208361
TI  - Bifurcations and global dynamics in a toxin-dependent aquatic population model.
AB  - The study of effects of environmental toxins on ecosystems is of great interest
      from both environmental and conservation points of view. In this paper, we
      present a global stability and bifurcation analysis of a toxin-dependent aquatic
      population model. Our analytical and numerical results show that both the
      environmental toxin level and the depuration capability of the population
      significantly affect the population persistence. The model exhibits a
      multifarious array of dynamics. While low levels of external toxin allow
      population persistence and high levels of toxin lead to an extirpation,
      intermediate toxin concentrations can produce very rich dynamics, such as
      transient oscillations, hysteresis, heteroclinic orbits, and a codimension-two
      bifurcation. In particular, a regime of bistability exists where the population
      is doomed to extinction or survival, depending on initial state of the system. As
      a practical implication of our study, the toxic effects of methylmercury on
      rainbow trout are scrutinized. The theory developed here provides a sound
      theoretical foundation for understanding the population effects of toxicity.

PMID- 29208360
TI  - The influence of soluble fragments of extracellular matrix (ECM) on tumor growth
      and morphology.
AB  - A major challenge in matrix-metalloproteinase (MMP) target validation and MMP
      inhibitor-drug development for anti-cancer clinical trials is to better
      understand their complex roles (often competing with each other) in tumor
      progression. While there is extensive research on the growth-promoting effects of
      MMPs, the growth-inhibiting effects of MMPs has not been investigated thoroughly.
      So we develop a continuum model of tumor growth and invasion including chemotaxis
      and haptotaxis in order to examine the complex interaction between the tumor and
      its host microenvironment and to explore the inhibiting influence of the
      gradients of soluble fragments of extracellular matrix (ECM) density on tumor
      growth and morphology. Previously, it was shown both computationally (in one
      spatial dimension) and experimentally that the chemotactic pull due to soluble
      ECM gradients is anti-invasive, contrary to the traditional view of the role of
      chemotaxis in malignant invasion [1]. With two-dimensional numerical simulation
      and using a level set based tumor-host interface capturing method, we examine the
      effects of chemotaxis on the progression and morphology of a tumor growing in
      nutrient-rich and nutrient-poor microenvironments which was not investigated
      before. In particular we examine how the geometry of the growing tumor is
      affected when placed in different environments. We also investigate the effects
      of varying ECM degradation rate, the production rate of matrix degrading enzymes
      (MDE), and the conversion of ECM into soluble ECM. We find that chemotaxis due to
      ECM-fragment gradients strongly influences tumor growth and morphology, and that
      the instabilities caused by tumor cell proliferation and haptotactic movements
      can be prevented if chemotaxis is sufficiently strong. The influence of
      chemotaxis and the above factors on tumor growth and morphology are found to be
      more prominent in nutrient-poor environments than in nutrient-rich environments.
      So we extend our investigations of these antinvasive chemotactic influences by
      examining the effects of cell-cell and cell-ECM adhesion and low proliferation
      rate for tumors growing in low-nutrient environments. We find that as the extent
      of chemotaxis increases, the effects of adhesion on tumor growth and shape become
      negligible. Under conditions of low cell mitosis, chemotaxis may cause the tumor
      to shrink, as the extent of chemotaxis increases. Both stable and unstable tumor
      shrinkage are predicted by our model. Unexpectedly, in some cases chemotaxis may
      contribute toward developing instability where haptotaxis alone induces stable
      growth.

PMID- 29208362
TI  - Feminizing effects of exposure to Corexit-enhanced water-accommodated fraction of
      crude oil in vitro on sex determination in Alligator mississippiensis.
AB  - Deepwater Horizon spilled over 200 million gallons of oil into the waters of the
      Gulf of Mexico in 2010. In an effort to contain the spill, chemical dispersants
      were applied to minimize the amount of oil reaching coastal shorelines. However,
      the biological impacts of chemically-dispersed oil are not well characterized,
      and there is a particular lack of knowledge concerning sublethal long-term
      effects of exposure. This study examined potential estrogenic effects of CWAF,
      Corexit 9500-enhanced water-accommodated fraction of oil, by examining its effect
      on estrogen receptors and sex determination in the American alligator, Alligator
      mississippiensis. The alligator exhibits temperature-dependent sex determination
      which is modulated by estrogen signals, and exposure to 17beta-estradiol (E2) and
      estrogenic compounds in ovo during the thermosensitive period of embryonic
      development can induce ovarian development at a male-producing temperature (MPT).
      CWAF induced transactivation up to 50% of the maximum induction by E2 via
      alligator estrogen receptors in vitro. To determine potential endocrine
      disrupting effects of exposure directly on the gonad, gonad-adrenal-mesonephric
      (GAM) organ complexes were isolated from embryos one day prior to the
      thermosensitive period and exposed to E2, CWAF, or medium alone in vitro for 8-16
      days at MPT. Both CWAF and E2 exposure induced a significant increase in female
      ratios. CWAF exposure suppressed GAM mRNA abundances of anti-Mullerian hormone
      (AMH), sex determining region Y-box 9, and aromatase, whereas E2 exposure
      suppressed AMH and increased Forkhead box protein L2 mRNA abundances in GAM.
      These results indicate that the observed endocrine-disrupting effects of CWAF are
      not solely estrogenically mediated, and further investigations are required.

PMID- 29208363
TI  - The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety
      and 1-year growth data.
AB  - BACKGROUND: For children with familial hypercholesterolemia (FH), UK guidelines
      recommend consideration of statin therapy by age 10 years and dietary and
      lifestyle advice to maintain an ideal body weight. OBJECTIVES: The objective of
      the study is to use the UK Paediatric Familial Hypercholesterolemia Register to
      determine: (1) the prevalence of plasma markers of liver toxicity and muscle
      damage in statin-treated FH children; (2) the prevalence of obesity in FH
      children compared to the UK general population; and (3) to compare growth rates
      in statin-treated and nontreated children. METHODS: Differences in registration
      and 1-year characteristics were compared by Mann-Whitney U tests. Age and gender
      body mass index percentiles were compared to UK children's growth charts.
      RESULTS: In 300 children (51% boys, 75% Caucasian, untreated mean [standard
      deviation] low-density lipoprotein cholesterol 5.50 [1.49] mmol/L), the
      proportion on statins varied significantly (P < .005) by age group (<5 years =
      0%, 5-10 years = 16.7%, 10-15 years = 57.1%, and >15 years = 73.2%). Statin
      treatment reduced low-density lipoprotein cholesterol by 31% (1.84 [1.43]
      mmol/L), and no child showed elevated levels of markers of liver toxicity or
      muscle damage. At registration, 16.9% of the FH children were overweight (>85th
      percentile) and 11.1% were obese (>95th percentile) vs reported in 21.2% in UK
      non-FH children. There was no difference in annual growth rate in statin vs no
      statin groups (age-adjusted weight increases 3.58 vs 3.53 kg; P = .91, height
      4.45 vs 4.60 cm P = .73). CONCLUSIONS: We show no evidence for statin-related
      safety or growth issues, but many FH children over the age of 10 years are not on
      statin treatment. Fewer UK children with FH are obese compared to UK non-FH
      children.

PMID- 29208364
TI  - Dopamine promotes cellular iron accumulation and oxidative stress responses in
      macrophages.
AB  - Iron is essential for many biological functions including neurotransmitter
      synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts
      tyrosine to dopamine and further to norepinephrine. As the shared chemical
      structure, called catechol, may potentially bind iron we questioned whether
      tyrosine derived hormones would impact on cellular iron homeostasis in
      macrophages, which are central for the maintenance of body iron homeostasis.
      Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect
      of catecholamines and found that only dopamine but neither tyrosine, nor
      norepinephrine, affected cellular iron homeostasis. Exposure of macrophages to
      dopamine increased the uptake of non-transferrin bound iron into cells. The
      expansion of intracellular iron upon dopamine treatment resulted in oxidative
      stress responses as evidenced by increased expression of nuclear factor erythroid
      2-related factor (Nrf2) and hypoxia inducible factor-1alpha. As a consequence,
      the transcriptional expression of stress response genes such as heme oxygenase-1
      and the iron export protein ferroportin1 were significantly increased. Genetic
      deletion of Nrf2 abolished these effects of dopamine. Dopamine directly affects
      cellular iron homeostasis by increasing iron incorporation into macrophages and
      subsequently promoting intracellular oxidative stress responses. Our observations
      are of interest for disorders involving dopamine and iron dyshomeostasis such as
      Parkinson's disease and restless legs syndrome, partly enlightening the
      underlying pathology or the therapeutic efficacy of dopamine agonists to overcome
      neuronal iron deficiency.

PMID- 29208365
TI  - Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior
      antileukemic activity against AML ex vivo.
AB  - Acute myeloid leukemia (AML) remains challenging to treat and needs more
      effective treatments. The PI3K/mTOR pathway is involved in cell survival and has
      been shown to be constitutively active in 50-80% of AML patients. However,
      targeting the PI3K/mTOR pathway results in activation of the ERK pathway, which
      also plays an important role in cell survival. In addition, AML cells often
      overexpress antiapoptotic Bcl-2 family proteins (e.g., Bcl-2), preventing cell
      death. Thus, our strategy here is to target the PI3K, mTOR (by VS-5584, a PI3K
      and mTOR dual inhibitor), ERK (by SCH772984, an ERK-selective inhibitor), and Bcl
      2 (by ABT-199, a Bcl-2-selective inhibitor) signaling network to kill AML cells.
      In this study, we show that while inhibition of PI3K, mTOR, and ERK showed
      superior induction of cell death compared to inhibition of PI3K and mTOR, the
      levels of cell death were modest in some AML cell lines and primary patient
      samples tested. Although simultaneous inhibition of PI3K, mTOR, and ERK caused
      downregulation of Mcl-1 and upregulation of Bim, immunoprecipitation of Bcl-2
      revealed increased binding of Bim to Bcl-2, which was abolished by the addition
      of ABT-199, suggesting that Bim was bound to Bcl-2 which prevented cell death.
      Treatment with combined VS-5584, SCH772984, and ABT-199 showed significant
      increase in cell death in AML cell lines and primary patient samples and
      significant reduction in AML colony formation in primary patient samples, while
      there was no significant effect on colony formation of normal human CD34+
      hematopoietic progenitor cells. Taken together, our findings show that inhibition
      of PI3K, mTOR, and ERK synergistically induces cell death in AML cells, and
      addition of ABT-199 enhances cell death further. Thus, our data support targeting
      the PI3K, mTOR, ERK, and Bcl-2 signaling network for the treatment of AML.

PMID- 29208366
TI  - Keto-adaptation enhances exercise performance and body composition responses to
      training in endurance athletes.

PMID- 29208367
TI  - The role of EpCAM in tumor progression and the clinical prognosis of endometrial
      carcinoma.
AB  - OBJECTIVE: EpCAM is a transmembrane glycoprotein that functions as an epithelial
      marker in endometrial tissues. However, the correlation between EpCAM and
      endometrial carcinoma (EC) is not clear. METHODS: This study investigated the
      association between EpCAM and EC. Immunohistochemistry staining and
      bioinformatics analysis disclosed the clinical importance of low EpCAM
      expression. The migratory ability of cells expressing low EpCAM levels was
      studied in transwell invasion assays in vitro and an orthotopic intra-uterine
      tumor injection model in vivo. The Connectivity MAP was used to identify drugs
      that effectively inhibit cells with low EpCAM expression. RESULTS: According to
      immunohistochemistry analysis results, low EpCAM expression was associated with
      an advanced stage and lymph node metastasis in patients with endometrioid EC, and
      high EpCAM expression favored survival. EpCAM silencing promoted cell invasion,
      and EpCAM re-expression in EpCAM-silenced EC cells attenuated their invasiveness.
      EpCAM suppression in an orthotopic uterine implantation model promoted the lymph
      node metastasis of EC cells. According to quantitative PCR and promoter reporter
      analyses, estrogen receptor alpha signaling regulated EpCAM expression by
      enhancing its promoter activity. As shown in the Connectivity MAP analysis,
      transamin inhibited the invasiveness of EpCAM-silenced EC cells. CONCLUSIONS: The
      loss of EpCAM may increase the malignancy of EC, and these findings provide new
      insights into the prognostic role of EpCAM in patients with EC.

PMID- 29208368
TI  - The end of life costs for Medicare patients with advanced ovarian cancer.
AB  - OBJECTIVE: To describe the Medicare payments at the end of life for patients with
      advanced ovarian cancer, and assess factors responsible for payment variation
      METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)
      Medicare database, we identified a cohort of women with stage III/IV epithelial
      ovarian cancer diagnosed between 1995 and 2007. We defined the end of life as the
      last 90days prior to death. Total medical costs were estimated from overall
      Medicare payments, and adjusted for geography and for inflation to the 2009 U.S.
      dollar. A generalized linear regression was performed to assess factors
      associated with variability in cost. RESULTS: Of 5509 patients, 78.9% died from
      ovarian cancer. In the 90days prior to death, 65.2% of patients had an inpatient
      admission, 53.7% received chemotherapy, 19.3% had a palliative procedure, and
      62.5% had hospice services. The mean total payment per patient in the last 90days
      of life was $24,073 (range 0-$484,119) over the study time period. The mean cost
      of inpatient admissions was $14,529 (range 0-$483,932). On a multivariate
      analysis, costs at the end of life did not vary based on length of patient
      survival (p=0.77). Factors associated with significantly increased costs in the
      last 90days of life were medical comorbidity, chemotherapy, time spent as an
      inpatient, and admissions associated with emergency room visits. CONCLUSIONS:
      Reducing the prescription of chemotherapy and increasing the use of hospice
      services for ovarian cancer patients at the end of life will aid in lowering
      costs.

PMID- 29208370
TI  - Design and development of a manual pump for bolus enteral nutrition.
AB  - INTRODUCTION: Enteral nutrition (EN) is based on administration of liquid
      solutions into the gastrointestinal tract using a tube. After identifying
      unsolved practical difficulties in administration of EN using volume syringes, a
      new device to overcome such technical difficulties was proposed. MATERIAL AND
      METHODS: Specific technologies (CAD, 3D printing) were used in collaboration with
      the PRODINTEC Foundation (Gijon, Asturias). Clarke Modet, a law firm specialized
      in intellectual property, provided legal advice on formulas for legal protection
      of the invention. RESULTS AND DISCUSSION: The resulting device is a manual pump
      for infusion of EN to patients that solves previously identified problems and is
      highly functional and compact. It would allow for comfortable and safe
      administration of solutions. Integration of a bottle into the device itself and
      pump dimensions facilitate transport and patient mobility. According to the
      described configuration, this invention has many advantages over the previously
      known procedures, such as a simpler administration within the field of
      intermittent EN, improving the standard nutritional support technique, which in
      this case is use of volume syringes. This would facilitate the work of caregivers
      while promoting patient self-care and autonomy. The pump was accredited novelty
      of design, inventive activity and industrial exploitation potential by the
      European Patent Office (EPO), to which a patent has been requested.

PMID- 29208369
TI  - Prophylactic 3-hour graduated infusion schedule minimizes risk of carboplatin
      hypersensitivity reactions - A prospective study.
AB  - OBJECTIVE: Aim of this study was observation of hypersensitivity reaction (HSR)
      frequency by using a 3-hour graduated infusion protocol with appropriate
      premedication as a prophylactic measure in patients with gynecological cancer
      receiving carboplatin retreatment in second line or above. None of the patients
      had experienced HSRs to platinum previously. METHOD: All the patients in this
      study received premedication with corticosteroids and anti-histamines followed by
      carboplatin as 3-hour graduated infusion. Carboplatin was administered either as
      monotherapy or in combination with other chemotherapeutic agents. RESULTS: Ninety
      nine patients with ovarian (n=71), fallopian tube (n=9), peritoneal (n=9) and
      other gynecological cancers (5 uterine cancer, 5 abdominal cancer of
      gynecological origin) were retreated by a total of 611cycles of carboplatin
      administered as monotherapy (210cycles) or combination regime (401cycles). HSRs
      were recorded in only 11cycles (1.8%) in a total of 11 patients. While 8 of these
      patients had grade 1or 2 reactions (8.1%), only 3 patients had grade 3 reactions
      (3%). After pause in the infusion and complete resolution of HSR symptoms, an
      attempt of retreatment using this infusion protocol with extra premedication was
      successful in 6 of these patients without any reoccurrence of HSRs. CONCLUSION:
      In this prospective study, we report that prophylactic 3-hour graduated infusion
      rate with appropriate premedication is associated with low frequency of HSRs in
      gynecological cancer patients requiring carboplatin retreatment in second line or
      above.

PMID- 29208371
TI  - Integrated semi-targeted metabolomics analysis reveals distinct metabolic
      dysregulation in pleural effusion caused by tuberculosis and malignancy.
AB  - BACKGROUND: Tuberculous pleural effusion (TPE) and malignant pleural effusion
      (MPE) are the 2 most frequent causes of exudative pleural effusions (PEs).
      However, the clinical differentiation is challenging. METHODS: Metabolic
      signatures in pleural effusion from 156 patients were profiled. An integrated
      semi-targeted metabolomics platform was incorporated for high throughput
      metabolite identification and quantitation. In this platform, orbitrap based mass
      spectrometry with data dependent MS/MS acquisition was applied in the analysis.
      In-house database containing ~1000MS/MS spectra were established and "MetaInt"
      was developed for metabolite alignment. RESULTS: Using this strategy, lower
      levels of amino acids, citric acid cycle intermediates and free fatty acids
      accompanied with elevated acyl-carnitines and bile acids were observed,
      demonstrating increased energy expenditure caused by TPE. Kynurenine pathway from
      tryptophan was significantly enhanced in TPE. The ratio of tryptophan/kynurenine
      exhibited decent performance in differentiating TPE from MPE with sensitivity of
      92.7% and specificity of 86.1%. After two further independent validations, it
      turns out that the ratio of tryptophan/kynurenine can be applied confidently as a
      potential biomarker together with adenosine deaminase (ADA) for clinical
      diagnosis of TPE. CONCLUSIONS: Conclusively, the integrated in-house platform for
      high throughput semi-targeted metabolomics analysis reliably identified great
      potential of tryptophan/kynurenine ratio as a novel diagnostic biomarker to
      distinguish pleural effusion caused by tuberculosis and malignancy.

PMID- 29208372
TI  - Different calibrator options may strongly influence the trueness of serum
      transferrin measured by Abbott Architect systems.

PMID- 29208373
TI  - Roles of maternal wnt8a transcripts in axis formation in zebrafish.
AB  - In early zebrafish development, the program for dorsal axis formation begins soon
      after fertilization. Previous studies suggested that dorsal determinants (DDs)
      localize to the vegetal pole, and are transported to the dorsal blastomeres in a
      microtubule-dependent manner. The DDs activate the canonical Wnt pathway and
      induce dorsal-specific genes that are required for dorsal axis formation. Among
      wnt-family genes, only the wnt8a mRNA is reported to localize to the vegetal pole
      in oocytes and to induce the dorsal axis, suggesting that Wnt8a is a candidate
      DD. Here, to reveal the roles of maternal wnt8a, we generated wnt8a mutants by
      transcription activator-like effector nucleases (TALENs), and established
      zygotic, maternal, and maternal zygotic wnt8a mutants by germ-line replacement.
      Zebrafish wnt8a has two open reading frames (ORF1 and ORF2) that are tandemly
      located in the genome. Although the zygotic ORF1 or ORF2 wnt8a mutants showed
      little or no axis-formation defects, the ORF1/2 compound mutants showed antero
      dorsalized phenotypes, indicating that ORF1 and ORF2 have redundant roles in
      ventrolateral and posterior tissue formation. Unexpectedly, the maternal wnt8a
      ORF1/2 mutants showed no axis-formation defects. The maternal-zygotic wnt8a
      ORF1/2 mutants showed more severe antero-dorsalized phenotypes than the zygotic
      mutants. These results indicated that maternal wnt8a is dispensable for the
      initial dorsal determination, but cooperates with zygotic wnt8a for ventrolateral
      and posterior tissue formation. Finally, we re-examined the maternal wnt genes
      and found that Wnt6a is an alternative candidate DD.

PMID- 29208374
TI  - The Application of 3D Printing in the Formulation of Multilayered Fast Dissolving
      Oral Films.
AB  - Fast-dissolving oral films (FDFs) provide an alternative approach to increase
      consumer acceptance by advantage of rapid dissolution and administration without
      water. Usually, FDFs require taste-masking agents. However, inclusion of these
      excipients could make developing the formulation a challenging task. Hence, this
      work employed fused-deposition modeling three-dimensional printing to produce
      single-layered FDFs (SLFDFs), or multilayered FDFs (MLFDFs) films, with taste
      masking layers being separated from drug layer. Filaments were prepared
      containing polyethylene oxide (PEO) with ibuprofen or paracetamol as model drugs
      at 60 degrees C. Also, filaments were produced containing polyvinyl alcohol and
      paracetamol at 130 degrees C. Furthermore, a filament was prepared containing PEO
      and strawberry powder for taste-masking layer. FDFs were printed at temperatures
      of 165 degrees C (PEO) or 190 degrees C (polyvinyl alcohol) with plain or mesh
      designs. High-performance liquid chromatography and mass spectroscopy analysis
      indicated active ingredient stability during film preparation process. SLFDFs had
      thicknesses as small as 197 +/- 21 MUm, and MLFDFs had thicknesses starting from
      298 +/- 15 MUm. Depending on the formulation and design, mesh SLFDFs presented
      disintegration time as short as 42 +/- 7 s, and this was 48 +/- 5 s for mesh
      MLFDFs. SLFDFs showed drug content uniformity in the range of 106.0%-112.4%. In
      conclusion, this study provides proof-of-concept for the manufacturing of FDFs by
      using 3D printing.

PMID- 29208375
TI  - Cancer control in Africa: infrastructure, not philanthropy.

PMID- 29208376
TI  - An action plan for cancer control in the USA.

PMID- 29208377
TI  - Priorities for cancer research in the USA.

PMID- 29208378
TI  - Implementing the Cancer Moonshot and beyond.

PMID- 29208379
TI  - Patients, data, and progress in cancer care.

PMID- 29208380
TI  - The Cancer Moonshot from a European perspective.

PMID- 29208381
TI  - CONVERTed or not: what are the barriers to implementing the evidence?

PMID- 29208382
TI  - CONVERTed or not: what are the barriers to implementing the evidence? - Author's
      reply.

PMID- 29208383
TI  - Neo-adjuvant chemotherapy alone or with regional hyperthermia for soft-tissue
      sarcoma.

PMID- 29208385
TI  - Physical fitness and cancer.

PMID- 29208384
TI  - Neo-adjuvant chemotherapy alone or with regional hyperthermia for soft-tissue
      sarcoma - Authors' reply.

PMID- 29208386
TI  - Cancer, checkpoint inhibitors, and confusion.

PMID- 29208387
TI  - Timing of androgen-deprivation therapy in prostate cancer.

PMID- 29208388
TI  - Timing of androgen-deprivation therapy in prostate cancer.

PMID- 29208389
TI  - Timing of androgen-deprivation therapy in prostate cancer - Author's reply.

PMID- 29208390
TI  - Adequate SIRT activity dose is as important as adequate chemotherapy dose.

PMID- 29208391
TI  - Adequate SIRT activity dose is as important as adequate chemotherapy dose -
      Authors' reply.

PMID- 29208392
TI  - Concordance between plasma-based and tissue-based next-generation sequencing in
      LOTUS.

PMID- 29208393
TI  - Neoadjuvant chemotherapy in oesophageal adenocarcinoma.

PMID- 29208394
TI  - Neoadjuvant chemotherapy in oesophageal adenocarcinoma.

PMID- 29208395
TI  - Neoadjuvant chemotherapy in oesophageal adenocarcinoma - Authors' reply.

PMID- 29208396
TI  - Correction to Lancet Oncol 2017; 18: 1502-11.

PMID- 29208397
TI  - Correction to Lancet Oncol 2017; 18: e315-29.

PMID- 29208399
TI  - Association between Extracellular Material and Biofilm Formation in Response to
      Sodium Hypochlorite by Clinical Isolates of Enterococcus faecalis.
AB  - INTRODUCTION: Extracellular material (ECM) surrounding Enterococcus faecalis may
      play a role in increasing resistance to environmental stresses. Our aim was to
      determine ECM levels in response to subminimal inhibitory concentrations of
      sodium hypochlorite (sub-MIC/NaOCl) or anaerobic growth and determine the impact
      on biofilm development. METHODS: From 37 E. faecalis clinical strains, 19 were
      selected according to their biofilm-producing ability by using a crystal violet
      biofilm assay: 10 strong, 4 intermediate, and 5 non-biofilm producers. Biofilm
      assays were subsequently performed on all strains when subjected to sub
      MIC/NaOCl. All strains were evaluated for ECM production under aerobic and
      anaerobic conditions and with sub-MIC/NaOCl. ECM production was assessed by using
      scanning electron microscopy. Double-blinded independent assessors were used to
      score levels of ECM production. The esp gene was detected by using polymerase
      chain reaction. Gelatinase activity was determined by using Todd-Hewitt and
      gelatin agar. RESULTS: In aerobic conditions, ECM was expressed in all strains.
      In the presence of sub-MIC/NaOCl, of the 10 strong biofilm producers, 5 increased
      their ECM production, and 4 showed increased biofilm growth. Two strains had less
      ECM production and showed decreased biofilm growth. One isolate demonstrated no
      observable changes. Most non-biofilm producers demonstrated no observable
      differences in ECM production, although 1 strain increased biofilm growth. ECM
      production in anaerobic conditions was highly variable. The esp gene (n = 15) and
      gelatinase activity (n = 7) were evident among the isolates. CONCLUSIONS: Clonal
      diversity among strains of E. faecalis suggests that some strong biofilm
      producers can upregulate ECM production and increase biofilm growth in response
      to sub-MIC/NaOCl.

PMID- 29208400
TI  - Influence of Cervical Preflaring on the Incidence of Root Dentin Defects.
AB  - INTRODUCTION: This study evaluated the influence of cervical preflaring on the
      incidence of root dentin defects after root canal preparation. METHODS: Extracted
      human maxillary central incisors were selected and allocated to 1 control group
      and 12 experimental groups (n = 15). Teeth in the control group were left
      unprepared, whereas the others were prepared using 2 reciprocating single-file
      systems (Reciproc and WaveOne [WO]), 3 full-sequence rotary systems (ProTaper
      Universal, ProTaper Next [PTN], and ProFile), and K-files driven by an
      oscillatory system, with and without cervical preflaring. Roots were then
      horizontally sectioned at 4, 8, and 12 mm from the apex, stained with 1%
      methylene blue, and viewed through a stereomicroscope at *25 magnification.
      Slices were inspected and the absence/presence of defects (fractures, partial
      cracks, and craze lines) recorded. Data were analyzed using Kolmogorov-Smirnov
      and Levene tests followed by the Tukey post hoc test at a significance level of P
      < .05. RESULTS: No root dentin defects were observed in the control group. WO was
      associated with a significantly higher number of defects than K-files, ProFile,
      and PTN (P < .05), but was not significantly different from Reciproc or ProTaper
      Universal (P > .05). Cervical preflaring significantly reduced the incidence of
      fractures and other defects in the WO and PTN groups (P < .05). CONCLUSIONS: All
      instruments caused root dentin defects, regardless of the enlargement or not of
      the cervical portion. Cervical preflaring was associated with a lower incidence
      of defects, mainly in root canals prepared with WO and PTN.

PMID- 29208401
TI  - Survival Rates from Fracture of Endodontically Treated Premolars Restored with
      Full-coverage Crowns or Direct Resin Composite Restorations: A Retrospective
      Study.
AB  - INTRODUCTION: The aim of the present study was to compare the survival rates
      against fracture of premolar endodontically treated teeth (ETT) restored with
      resin composite or crowns and to identify risk factors associated with the
      fracture. METHODS: Data from dental records and radiographs of premolar ETT with
      postendodontic restorations (ie, resin composite or crowns) were collected
      between 2012 and 2016 and selected following selected inclusion and exclusion
      criteria. Tooth location, type of restoration, number of proximal contacts, and
      amount of tooth surface loss were recorded. The incidence and restorability of
      postendodontic fractures were identified. Survival rates against fracture of the
      2 restoration types were calculated using Kaplan-Meier survival analysis. Any
      potential factors associated with fractures were identified using Cox
      proportional hazards models. RESULTS: The survival rate against fracture of ETT
      restored with crowns (95.1%) was higher than resin composite (77.0%). ETT
      restored with resin composite with 1 or 2 tooth surface losses and 2 proximal
      contacts had a high survival rate of 88.5% that was not significantly different
      from ETT with crowns. A higher incidence of restorability after fracture was
      observed in teeth restored with resin composite than crowns. The type of
      restoration and number of proximal contacts were identified as potential risk
      factors associated with fracture incidence. CONCLUSIONS: The survival rate
      against fracture of ETT restored with crowns was higher than resin composite.
      However, ETT with 1 or 2 tooth surface losses and 2 proximal contacts and
      restored with resin composite showed a high survival rate that was comparable
      with ETT restored with crowns.

PMID- 29208402
TI  - Anesthetic Efficacy of Supine and Upright Positions for the Inferior Alveolar
      Nerve Block: A Prospective, Randomized Study.
AB  - INTRODUCTION: It has been recommended to place patients in an upright position
      after administration of an inferior alveolar nerve block (IANB), theoretically
      allowing the anesthetic to diffuse in an inferior direction and resulting in
      better pulpal anesthesia. The purpose of this study was to compare an upright
      versus a supine position on the success of pulpal anesthesia when an IANB was
      administered in asymptomatic teeth. METHODS: One hundred ten asymptomatic
      subjects were randomly given IANBs by using 2% lidocaine with 1:100,000
      epinephrine while they were in an upright position and supine position at 2
      different appointments spaced at least 2 weeks apart. Pulpal anesthesia was
      measured in the molars, premolars, and incisors with an electric pulp tester in 4
      minute cycles for 60 minutes. Anesthetic success was defined as the subject
      achieving 2 consecutive 80 readings within 15 minutes of the injection and
      sustaining the 80 reading for 60 minutes. Success was analyzed by using a mixed
      model logistic regression. RESULTS: Pulpal anesthesia for the supine position was
      not statistically more successful than the upright position in the second molars
      (73% vs 65%), first molars (59% vs 54%), lateral incisors (28% vs 23%), and
      central incisors (11% vs 8%), respectively. The supine position significantly
      improved success in the second premolars (63% vs 53%) and first premolars (75% vs
      64%). CONCLUSIONS: The supine and upright positions were equally successful in
      the molars and anterior teeth. The supine position was more successful in the
      premolars. However, clinically, neither position for the IANB administration
      would provide complete pulpal anesthesia.

PMID- 29208403
TI  - Efficacy of Standard Dose R-CHOP Alternating With R-HDAC Followed by Autologous
      Hematopoietic Cell Transplantation as Initial Therapy of Mantle Cell Lymphoma, a
      Single-Institution Experience.
AB  - BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly
      treated with induction chemotherapy followed by high-dose chemotherapy and
      autologous hematopoietic cell transplantation (AHCT). Induction regimens with
      modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,
      and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more
      effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of
      the Nordic protocol using standard, rather than higher dose R-CHOP, alternating
      with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already
      treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of
      rituximab plus HDAC. We herein report our experience with 28 patients treated
      with this regimen who proceeded to AHCT, and compare their outcomes with patients
      treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA
      (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with
      methotrexate, and cytarabine; n = 21), before AHCT. RESULTS: With a median follow
      up duration of 26 months, our data show that this modification of the Nordic
      regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year
      progression-free and overall survival rates of 69% and 75%, respectively).
      CONCLUSION: By using a less intense induction, this regimen can serve as a
      platform for combined use of novel agents, with less risk of additive toxicity.

PMID- 29208404
TI  - Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus.
AB  - The aim of this work was to know whether naringin (NA) could prevent the bone
      complications in a model of streptozotocin (STZ) induced diabetes. Rats were
      divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and
      4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone
      histomorphometry and histology as well as TRAP staining were done in tibia.
      Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD
      and catalase activities were assayed in bone marrow from femur. The data showed
      that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40
      and NA80 normalized the trabecular number and the trabecular separations. An
      increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was
      blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the
      NA80 treatment allowed to reach the control values. NA normalized the SOD and
      catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA
      avoids alterations in the physical properties and microstructure of bone from STZ
      rats probably by stimulation of osteoblastogenesis, inhibition of the
      osteoclastogenesis and adipogenesis via blocking the oxidative stress.

PMID- 29208405
TI  - Emergence of a Klebsiella pneumoniae ST392 clone harbouring KPC-3 in an Italian
      transplantation hospital.

PMID- 29208406
TI  - Macrophage depletion by liposome-encapsulated clodronate suppresses seizures but
      not hippocampal damage after acute viral encephalitis.
AB  - Viral encephalitis is a major risk factor for the development of seizures and
      epilepsy, but the underlying mechanisms are only poorly understood. Mouse models
      such as viral encephalitis induced by intracerebral infection with Theiler's
      virus in C57BL/6 (B6) mice allow advancing our understanding of the immunological
      and virological aspects of infection-induced seizures and their treatment.
      Previous studies using the Theiler's virus model in B6 mice have indicated that
      brain-infiltrating inflammatory macrophages and the cytokines released by these
      cells are key to the development of acute seizures and hippocampal damage in this
      model. However, approaches used to prevent or reduce macrophage infiltration were
      not specific, so contribution of other mechanisms could not be excluded. In the
      present study, we used a more selective and widely used approach for macrophage
      depletion, i.e., systemic administration of clodronate liposomes, to study the
      contribution of macrophage infiltration to development of seizures and
      hippocampal damage. By this approach, almost complete depletion of monocytic
      cells was achieved in spleen and blood of Theiler's virus infected B6 mice, which
      was associated with a 70% decrease in the number of brain infiltrating
      macrophages as assessed by flow cytometry. Significantly less clodronate liposome
      treated mice exhibited seizures than liposome controls (P<0.01), but the
      development of hippocampal damage was not prevented or reduced. Clodronate
      liposome treatment did not reduce the increased Iba1 and Mac3 labeling in the
      hippocampus of infected mice, indicating that activated microglia may contribute
      to hippocampal damage. The unexpected mismatch between occurrence of seizures and
      hippocampal damage is thought-provoking and suggests that the mechanisms involved
      in degeneration of specific populations of hippocampal neurons in encephalitis
      induced epilepsy are more complex than previously thought.

PMID- 29208407
TI  - Dehydrocavidine attenuates d-galactose induced learning and memory impairment in
      rats.
AB  - OBJECTIVE: Dehydrocavidine (DEH) is the major component of a plant corydalis
      saxicola Bunting, which is used to treat the patients with hepatic disorders,
      there is still no report about the effect of DEH on the brain disorder. In this
      study, the effect and mechanism of DEH on d-galactose (d-gala) induced learning
      and memory impairment in rats was investigated. METHODS: A learning and memory
      impairment rat model was employed by chronic intraperitoneal injection of d-gala
      and intragastric administration of DEH, then Morris water maze test was used to
      investigate the effect of DEH on learning and memory impairment, Golgi stain and
      biochemical methods, real time PCR were used to investigate underlying mechanism.
      RESULTS: Intraperitoneal injection of d-gala could induced severe learning and
      memory impairment in rats, intragastric administration of DEH could effectively
      attenuates these deficits. Golgi staining showed DEH supplementary could restored
      the density of spines to 5.7+/-1.16 spines per 10MUm in the DEH+d-gala group
      (p<0.05). DEH supplementary administration reversed the lipid peroxides and
      restored the enzymes activities to reduce oxidative damage (p<0.05). DEH
      supplementary administration could reduced the production of NO and PGE2 and the
      mRNA expression of iNOS and COX-2 (p<0.05). CONCLUSIONS: DEH could attenuates d
      gala induced learning and memory impairment in rats by enhancing synaptic
      plasticity, reducing oxidative damage and limiting the neuroinflammation.

PMID- 29208398
TI  - Future cancer research priorities in the USA: a Lancet Oncology Commission.
AB  - We are in the midst of a technological revolution that is providing new insights
      into human biology and cancer. In this era of big data, we are amassing large
      amounts of information that is transforming how we approach cancer treatment and
      prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in
      the USA arrived at a propitious moment in the advancement of knowledge, providing
      nearly US$2 billion of funding for cancer research and precision medicine. In
      2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed
      to exploit new advances in cancer diagnosis, prevention, and treatment. Those
      recommendations provided a high-level view of how to accelerate the conversion of
      new scientific discoveries into effective treatments and prevention for cancer.
      The US National Cancer Institute is already implementing some of those
      recommendations. As experts in the priority areas identified by the BRP, we
      bolster those recommendations to implement this important scientific roadmap. In
      this Commission, we examine the BRP recommendations in greater detail and expand
      the discussion to include additional priority areas, including surgical oncology,
      radiation oncology, imaging, health systems and health disparities, regulation
      and financing, population science, and oncopolicy. We prioritise areas of
      research in the USA that we believe would accelerate efforts to benefit patients
      with cancer. Finally, we hope the recommendations in this report will facilitate
      new international collaborations to further enhance global efforts in cancer
      control.

PMID- 29208408
TI  - Personalized management of bipolar disorder.
AB  - Bipolar disorder (BD) is one of the most serious psychiatric disorders. The rates
      of disability, the risk of suicide attempts and their high lethality, as well as
      frequent and severe psychiatric and medical comorbidities, put it among the major
      causes of mortality and disability worldwide. At the same time, many patients can
      do well when treated properly. In this review, we focus on those aspects of the
      clinical care that offer the potential of individualized approach, in the context
      of the recent technology driven advances in the comprehension of the
      neurobiological underpinnings of BD. We first review those clinical and
      biological factors that can help identifying individuals at high risk of
      developing BD. Among these are a family history of BD and/or completed suicide,
      prodromal symptoms (in childhood and/or adolescence) such as anxiety and mood
      lability, early onset, and poor response to antidepressants. Panels of genetic
      markers are also being studied to identify subjects at risk for BD. Further,
      neuroimaging studies have found an increased gray matter density in the right
      Inferior Frontal Gyrus (rIFG) as a possible risk marker of BD. We then examine
      clinical factors that influence the initiation, selection and possibly
      discontinuation of long-term treatment. Lastly, we discuss the risk of side
      effects in BD, and their relevance for treatment adherence and for treatment
      monitoring. In summary, we discuss how a personalized approach in BD can be
      implemented through the identification of specific clinical and molecular
      predictors. We show that the realization of a personalized management of BD is
      not only of a theoretical value, but has substantial clinical repercussions,
      resulting in a significant reduction of the long-term morbidity and mortality
      associated to BD.

PMID- 29208409
TI  - Direct fermentation of Jerusalem artichoke tuber powder for production of l
      lactic acid and d-lactic acid by metabolically engineered Kluyveromyces
      marxianus.
AB  - An efficient production system for optically pure l- and d-lactic acid (LA) from
      Jerusalem artichoke tuber powder (JAP) was developed by metabolic engineering of
      Kluyveromyces marxianus. To construct LA-producing strains, the ethanol
      fermentation pathway of K. marxianus was redirected to LA production by
      disruption of KmPDC1 and expression of l- and d-lactate dehydrogenase (LDH) genes
      derived from Lactobacillus plantarum under the control of the K. marxianus
      translation elongation factor 1alpha promoter. To further increase the LA titer,
      the l-LA and d-LA consumption pathway of host strains was blocked by deletion of
      the oxidative LDH genes KmCYB2 and KmDLD1. The recombinant strains produced
      130g/L l-LA and 122g/L d-LA by direct fermentation from 230g/L JAP containing
      140g/L inulin, without pretreatment or nutrient supplementation. The conversion
      efficiency and optical purity were ?>95% and ?>99%, respectively. This system
      using JAP and the inulin-assimilating yeast K. marxianus could lead to a cost
      effective process for the production of LA.

PMID- 29208410
TI  - Application of heat compensation calorimetry to an E. coli fed-batch process.
AB  - The application of biocalorimetry to fermentation processes offers advantageous
      insights, while being less complex compared to other, sophisticated PAT
      solutions. Although the general concept is established, calorimetric methods vary
      in detail. In this work, a special approach, called heat compensation
      calorimetry, was applied to an E. coli fed-batch process. Much work has been done
      for batch processes, proving the validity and accuracy of this calorimetric mode.
      However, the adaption of this strategy to fed-batch processes has some
      implications. In the first section of this work, batch fermentations were
      performed, comparing heat capacity calorimetry to the compensation mode. Both
      processes showed very good agreement by means of growth behavior. The heat
      related differences, e.g. temperature profiles, were obvious. In addition, the
      impact of the chosen mode on the calculation of in-process heat transfer
      coefficients was shown. Finally, a fed-batch fermentation was performed. The
      compensation mode was kept sufficiently, up to the point where the metabolic heat
      production accelerated strongly. Controller tuning was a neuralgic point, which
      would have needed further optimization under these conditions. Nevertheless, in
      the present work it was possible to realize a working compensation process while
      demonstrating critical aspects that must be considered when establishing such
      approach.

PMID- 29208411
TI  - Distribution of NADPH-diaphorase reactivity in the central nervous system of the
      common toad (Bufo bufo).
AB  - We examined the distribution of nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d)-reactive elements in the central nervous system (CNS) of the
      common toad, Bufo bufo. The investigation involved adult male and female toads
      collected during the breeding season. Labeled neurons of different morphological
      appearances (weakly or darkly stained, unipolar, bipolar, and multipolar) and
      fibers were observed across all subdivisions of the amphibian brain. Overall, a
      similar distribution of NADPH-d-labeled neurons was observed in the brain of male
      and female toads. In the secondary prosencephalon NADPH-d-labeled neurons were
      observed in the olfactory bulbs, pallial regions, nucleus accumbens, diagonal
      band of Broca, septum, striatum, amygdala, suprachiasmatic and magnocellular
      preoptic nuclei, dorsal and ventral hypothalamus. In the diencephalon, NADPH-d
      positive neurons were seen in the anterior thalamic nuclei, ventromedial and
      ventrolateral nuclei, central and lateral thalamic nuclei, posterior tubercle,
      posterodorsal division of the lateral thalamic nucleus, and in the pretectal and
      pretoral gray. In the mesencephalon, heavily stained neurons were present in the
      anterodorsal and anteroventral tegmental nuclei, magnocellular, principal and
      laminar nuclei of the torus semicircularis, and nucleus profundus mesencephali.
      In the isthmus, stained cells were observed medially and ventrally in the
      posterodorsal and posteroventral tegmental nuclei. In the rhombencephalon,
      numerous NADPH-d-stained neurons were distributed in the cerebellar nucleus,
      sensory and descending trigeminal nuclei, motor nuclei of the glossopharyngeal
      and vagus nerves, the nucleus of the solitary tract, nuclei of the hypoglossal
      and octaval nerves, dorsal column nucleus, central gray region, and in reticular
      formation. However, the complete absence of NADPH-d-stained neurons in the
      cerebellar cortex was an unusual feature observed in this study. The widespread
      distribution of NADPH-d staining in diverse cell types, belonging to a variety of
      neuronal systems suggests a widespread role for NADPH-d in modulating diverse
      functions, including sensory coding in the amphibian nervous system.

PMID- 29208412
TI  - Impact of the surface charge of polydiacetylene micelles on their interaction
      with human innate immune protein C1q and the complement system.
AB  - Polydiacetylene (pDA) micelles have been demonstrated to be effective drug
      carriers for cancer therapy in mouse model. However, little is known about their
      interaction with the human complement system, which constitutes an important part
      of the innate immune system and can cause severe hypersensitivity reactions.
      Herein, we investigate the influence of micelle surface charge on the binding of
      complement protein C1q, the target recognition unit that activates the classical
      complement pathway and performs a range of other important physiological
      functions. Besides the classical pathway, we also investigate the surface charge
      effect on complement activities through the other activation pathways, namely,
      the MBL-dependent lectin pathway and the alternative pathway. We synthesized
      three samples of pDA micelles bearing neutral, anionic, and cationic surface
      charge motifs, respectively. Surface plasmon resonance showed that none of these
      micelles interacted with C1q. Results from serum complement activation assays
      indicated that all micelles were inert to complement, except for the anionic pDA
      micelles, which activated the alternative pathway.

PMID- 29208413
TI  - Characterization of ML0314c of Mycobacterium leprae and deciphering its role in
      the immune response in leprosy patients.
AB  - Mycobacterium leprae has a reduced genome size due to the reductive evolution
      over a long period of time. Lipid metabolism plays an important role in the life
      cycle and pathogenesis of this bacterium. In comparison to 26 lip genes (Lip A-Z)
      of M. tuberculosis, M. leprae retained only three orthologs indicating their
      importance in its life cycle. ML0314c (LipU) is one of them. It is conserved
      throughout the mycobacterium species. Bioinformatics analysis showed the presence
      of an alpha/beta hydrolase fold and 'GXSXG' characteristic of the
      esterases/lipases. The gene was expressed in E. coli and purified to homogeneity.
      It showed preference towards short chain esters with pNP-acetate as the preferred
      substrate. The enzyme showed optimal activity at 45 degrees C and pH8.0. ML0314c
      protein was stable between temperatures ranging from 20 to 60 degrees C and pH5.0
      8.0, i.e., relatively acidic and neutral conditions. The active site residues
      predicted bioinformatically were confirmed to be Ser168, Glu267, and His297 by
      site directed mutagenesis. E-serine, DEPC and Tetrahydrolipstatin (THL)
      completely inhibited the activity of ML0314c. The protein was localized in cell
      wall and extracellular medium. Several antigenic epitopes were predicted in
      ML0314c. Protein elicited strong humoral immune response in leprosy patients,
      whereas, a reduced immune response was observed in the relapsed cases. No humoral
      response was observed in treatment completed patients. Overexpression of ml0314c
      in the surrogate host M. smegmatis showed marked difference in the colony
      morphology and growth rate. In conclusion, ML0314c is a secretary carboxyl
      esterase that could modulate the immune response in leprosy patients.

PMID- 29208414
TI  - Analysis of the SNP loci around transcription start sites related to goat
      fecundity trait base on whole genome resequencing.
AB  - Genome flanking regions surrounding transcription start sites (TSSs) are critical
      for the regulation of gene expression, containing many translational regulatory
      elements. To investigate whether critical single nucleotide polymorphisms (SNPs)
      exist around TSSs in the dairy goat genome, we performed high throughput DNA
      sequencing to compare two dairy goat groups with discrepant litter sizes. After
      genome mapping, SNP calling, and annotation, we screened the SNPs within 2kb
      scales surrounding annotated TSSs in high fecundity (HF) and low fecundity (LF)
      groups, respectively. We attempted to identify distinct SNPs and motifs near the
      TSSs in both groups. The SNPs near the TSSs most were consistent; 318 new SNPs
      were uncovered in the HF group, of which 305 were heterozygote SNPs, 13 were
      homozygote SNPs, and majority of which were distributed on chromosome 2 and 29.
      After validation by Sanger sequencing we found that a SNP in CHI16: 27612330 C>A
      in the PSEN2 gene presented an A/A genotype in the HF group and an A/A or A/C
      genotype in the LF group. In conclusion, our study provides insightful
      information into the dairy goat genomic variations surrounding TSSs, which may
      contribute to enhanced litter size. Based on comparison studies of SNPs exist
      around transcription start sites between high fecundity group and low fecundity
      group. Our finding provides insights concerning the goat litter size phenotypic
      and will promote future goat breeding.

PMID- 29208415
TI  - Guideline on terminology and definitions of updating clinical guidelines: The
      Updating Glossary.
AB  - OBJECTIVE: The Guidelines International Network (G-I-N) Updating Guidelines
      Working Group launched an initiative to develop a glossary (the Updating
      Glossary) with domains, terms, definitions, and synonyms related to updating of
      clinical guidelines (CGs). STUDY DESIGN AND SETTING: The steering committee
      developed an initial list of domains, terms, definitions, and synonyms through
      brainstorming and discussion. The panel members participated in three rounds of
      feedback to discuss, refine, and clarify the proposed terms, definitions, and
      synonyms. Finally, the panel members were surveyed to assess their level of
      agreement regarding the glossary. RESULTS: Eighteen terms were identified and
      defined: (1) continuous updating, (2) decision to update, (3) fixed updating, (4)
      full updating, (5) impact of the new evidence, (6) partial updating, (7)
      prioritization process, (8) reporting process, (9) signal for an update, (10)
      surveillance process, (11) time of validity, (12) timeframe, (13) tools and
      resources, (14) up to date, (15) update cycle, (16) update unit, (17) updated
      version, and (18) updating strategy. Consensus was reached for all terms,
      definitions, and synonyms (median agreement scores >= 6); except for one term.
      CONCLUSIONS: The G-I-N Updating Guidelines Working Group assembled the Updating
      Glossary to facilitate and improve the knowledge exchange among CGs developers,
      researchers, and users.

PMID- 29208417
TI  - Multiple digit melanonychia: Examine the scalp.

PMID- 29208416
TI  - Statin use and risk of skin cancer.
AB  - BACKGROUND: Statins are among the most commonly used medications in the United
      States, and statin use is associated with increased risk of basal cell carcinoma
      (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by
      lack of adjustment for important confounders. OBJECTIVE: Examine the relation
      between statins and skin cancer risk in the Nurses' Health Study and Health
      Professionals Follow-up Study. METHODS: Cox proportional hazards regression was
      used to evaluate associations. RESULTS: During follow-up (2000-2010), we
      documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high
      cholesterol level was not associated with risk of BCC (pooled multivariable
      adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC
      (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin
      use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR,
      1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a
      trend toward higher BCC risk with longer duration of statin use in men (P trend =
      .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data.
      CONCLUSION: History of high cholesterol level was not associated with skin cancer
      risk. Longer duration of statin use was associated with a trend toward higher BCC
      risk in men.

PMID- 29208418
TI  - Left Atrial Volumes and Strain in Healthy Children Measured by Three-Dimensional
      Echocardiography: Normal Values and Maturational Changes.
AB  - BACKGROUND: Assessment of left atrial (LA) size and function is important in a
      number of pediatric cardiac conditions including those affecting the diastolic
      performance of the left ventricle. Measurements of LA volume and strain by two
      dimensional echocardiography rely upon inaccurate geometric assumptions and are
      hampered by out-of-plane motion. The objective of this study was to characterize
      LA volumes and strain by three-dimensional echocardiography in healthy children.
      METHODS: LA volumes and strain were retrospectively measured by three-dimensional
      echocardiography in healthy children with no known structural or functional heart
      disease using a commercial speckle-tracking package applied to the LA to compute
      maximum volume (Vmax), minimum volume (Vmin), ejection volume (LAEV), ejection
      fraction (LAEF), and the following components of global strain: 3D principal
      (3DS), longitudinal (GLS), and circumferential (GCS). RESULTS: The study
      population included 196 normal subjects (median age, 12 years; range, 4 days to
      20.9 years). Vmax, Vmin, and LAEV increased with age and body surface area.
      Significant age-related declines were present in all measured functional indices
      including LAEF, 3DS, GLS, and GCS. Analysis of a subset of 50 subjects showed
      excellent agreement between Vmax derived by three-dimensional and two-dimensional
      biplane area-length method. Regression equations with standard deviations were
      generated to enable calculation of Z scores. CONCLUSIONS: LA volume and
      functional indices can be reliably calculated using a commercial three
      dimensional analysis software. All components of LA strain decline modestly with
      age. Normative data generated in this study have the potential to greatly enhance
      the utility of three-dimensional echocardiography-derived measurements in a wide
      range of cardiac pathologies.

PMID- 29208419
TI  - Planning of Polish physician workforce - Systemic inconsistencies, challenges and
      possible ways forward.
AB  - BACKGROUND: Poland has the lowest number of physicians per 1000 population
      (2.2/1000) in the EU. This is accompanied by a considerable migration rate of
      Polish physicians to other EU countries (estimated at above 7%). Among other
      consequences, this results in waiting lists and unmet health needs. OBJECTIVE:
      The aim of this article is an identification of the main challenges for physician
      workforce planning in Poland. METHODS: The authors analysed national and
      international documents, reports, official statements, publications and
      statistical databases. MAIN FINDINGS: In Poland health workforce planning is
      inadequate and insufficient. There is no formal structure and no strategy
      regarding human resource planning or regular forecasts for the health workforce,
      which results in many negative effects for the healthcare system. Currently the
      shortage of physicians in some specialties is becoming one of the most important
      reasons for limited access to care and lengthening the average wait time.
      CONCLUSIONS: To improve this situation operational and strategic actions should
      be undertaken without unnecessary delay. Effective and close cooperation between
      key stakeholders is needed. Health workforce planning needs to become one of the
      key building blocks of the Polish health system's reforms, strongly connected to
      the other functions of the health system. It is essential for Poland to follow
      available good practices in health workforce planning.

PMID- 29208420
TI  - The inhibitor of connexin Cx36 channels, mefloquine, inhibits voltage-dependent
      Ca2+ channels and insulin secretion.
AB  - The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap
      junctions and hemichannels and has thus become a tool to investigate their
      physiological relevance in pancreatic islets. In view of earlier reports on a
      KATP channel-block by mefloquine, the specificity of mefloquine as a
      pharmacological tool was investigated. Mouse pancreatic islets and single beta
      cells were used to measure membrane potential, whole cell currents, Ca2+ channel
      activity, cytosolic Ca2+ concentration ([Ca2+]i) and insulin secretion.
      Mefloquine was tested in the concentration range of 5-50 MUM 25 MUM mefloquine
      was as effective as 500 MUM tolbutamide to depolarize the plasma membrane of beta
      cells, but did not induce action potentials. Rather, it abolished tolbutamide
      induced action potentials and the associated increase of [Ca2+]i. In the range of
      5-50 MUM mefloquine inhibited voltage-dependent Ca2+ currents in primary beta
      cells as effectively as 1 MUM nisoldipine, a specific blocker of L-type Ca2+
      channels. The Ca2+ channel opening effect of Bay K8644 was completely antagonized
      by mefloquine. Likewise, the increase of [Ca2+]i and of insulin secretion
      stimulated by 40 mM KCl, but not that by 30 mM glucose was antagonized by 50 MUM
      mefloquine. Neither at 5 MUM nor at 50 MUM did mefloquin stimulate insulin
      secretion at basal glucose. In conclusion, mefloquine blocks KATP channels and L
      type Ca2+ channels in pancreatic beta cells in the range from 5 to 50 MUM. Thus
      it inhibits depolarization-induced insulin secretion, but in the presence of a
      stimulatory glucose concentration additional effects of mefloquine, possibly on
      intracellular Ca2+ mobilization, and the metabolic amplification by glucose
      permit a sustained rate of secretion.

PMID- 29208421
TI  - Is testing for postprandial hyperinsulinemic hypoglycemia after gastric bypass
      necessary?
AB  - INTRODUCTION: Postprandial hyperinsulinemic hypoglycemia (pHH) is an increasingly
      reported complication after Roux-en-Y gastric bypass (RYGB). As pHH can cause
      life-threatening emergencies if occurring without warning symptoms, challenge
      testing may detect patients at risk. The study objective was to determine the
      frequency of occurrence of pHH with or without symptoms of hypoglycemia after
      RYGB. METHODS: We undertook an observational cohort study of consecutive,
      unselected patients approximately one year after uncomplicated RYGB. To simulate
      normal habits, all patients received a standardized carbohydrate-rich solid mixed
      meal. Plasma glucose and insulin were measured at 30, 60, 90, 120, and 150 min
      thereafter. Symptoms were classified as autonomous or neuroglycopenic. Patients
      with hypoglycemia (plasma glucose <3.0 mmol/L [55 mg/dL]), were tested a second
      time with a protein-rich solid mixed meal. RESULTS: 113 patients were included.
      Total weight loss at the first follow-up check (14 +/- 0.4 months) was 33.97 +/-
      9.3%. After the carbohydrate-rich meal, glucose dropped to <3.0 mmol/L in 13.2%
      (n = 15) of patients vs no drop to <3.0 mmol/L after a protein-rich meal. The pHH
      occurred in 11.5% (n = 13) of patients. Asymptomatic patients (5.3%, n = 6)
      carried an increased risk (p = 0.008) for pHH. One patient needed emergency
      treatment after sudden loss of consciousness after the carbohydrate-rich meal.
      CONCLUSIONS: The occurrence of pHH was quite high in our study population with
      11.5% thereof 5.3% asymptomatic. We therefore suggest that detection of these
      patients warrants a screening of patients after RYGB. At-risk patients should
      than be adequately advised to avoid carbohydrate-rich meals in order to optimize
      risk management.

PMID- 29208422
TI  - Support vector machine-based classification of first episode drug-naive
      schizophrenia patients and healthy controls using structural MRI.
AB  - Although regional brain deficits have been demonstrated in schizophrenia patients
      by structural MRI studies, one important question that remains largely unanswered
      is whether the complex and subtle deficits revealed by MRI could be used as
      objective biomarkers to discriminate patients from healthy controls individually.
      To address this question, a total of 326 right-handed participants were
      recruited, including 163 drug-naive first-episode schizophrenia (FES) patients
      and 163 demographically matched healthy controls. High-resolution anatomic data
      were acquired from all subjects and processed via Freesurfer software to obtain
      cortical thickness and surface area measurements. Subsequently, the Support
      Vector Machine (SVM) was used to explore the potential utility for cortical
      thickness and surface area measurements in the differentiation of individual
      patients and healthy controls. The accuracy of correct classification of patients
      and controls was 85.0% (specificity 87.0%, sensitivity 83.0%) for surface area
      and 81.8% (specificity 85.0%, sensitivity 76.9%) for cortical thickness (p<0.001
      after permutation testing). Regions contributing to classification accuracy
      mainly included the gray matter in default mode, central executive, salience, and
      visual networks. Current findings, in a sample of never-treated FES patients,
      suggest that the patterns of illness-related gray matter changes has potential as
      a biomarker for identifying structural brain alterations in individuals with
      schizophrenia. Future prospective studies are needed to evaluate the utility of
      imaging biomarkers for research and potentially for clinical purpose.

PMID- 29208423
TI  - Delusions of control in schizophrenia: Resistant to the mind's best trick?
AB  - The existence of a free will is fiercely debated in neuroscience and philosophy.
      The debate has great impact on society and our self-understanding as human
      beings. Behavioral and electrophysiological data have challenged the intuitive
      assumption that human behavior is the result of conscious intentions. This notion
      has important implications for delusions of control in schizophrenia, where
      patients experience bodily movements as not being controlled by themselves.
      Current theories explain control delusions as a deficit to perceive certain
      aspects of motor control, but many findings are inconsistent with this idea.
      Here, an alternative view is proposed: Control delusions might be triggered by an
      even more veridical perception of the temporal order of intentions and actions.
      This hypothesis is supported by evidence that (a) conscious intentions in healthy
      subjects are often based on retrospective inferences, (b) temporal recalibrations
      of conscious percepts occur in healthy subjects and are disturbed in
      schizophrenia and (c) basic perceptual functions of schizophrenic patients are
      less influenced by expectations and therefore they can sometimes be closer to
      physical reality than those of healthy subjects.

PMID- 29208424
TI  - Evolutionary studies on the betaretrovirus RERV-H in the Leporidae family reveal
      an endogenization in the ancestor of Oryctolagus, Bunolagus and Pentalagus at 9
      million years ago.
AB  - RERV-H was first identified in human tissues and mistaken for a human exogenous
      retrovirus. However, the integration sites carried by this virus showed that it
      was instead a European rabbit (Oryctolagus cuniculus) endogenous retrovirus. The
      first clones retrieved from European rabbit samples represented defective
      proviruses, although estimation of proviral copy numbers found in the European
      rabbit genome ranged from hundreds to thousands. Screening for the presence of
      RERV-H showed the absence of the virus in two other lagomorphs, pika (Ochotona)
      and hares (Lepus), which diverged from rabbits about 35 and 12 million years ago,
      respectively. Using a PCR-based approach, samples of seven different Lagomorph
      genera were tested for the presence of RERV-H. It was possible to amplify a
      proviral fragment corresponding to RNaseH from Oryctolagus, Bunolagus and
      Pentalagus genomic samples. The amplification of proviral DNA in species other
      than Oryctolagus revealed that this virus was endogenized in their common
      ancestor, roughly 9 million years ago. Using the European rabbit genome sequence
      OryCun2.0, it was possible to find multiple copies spread throughout the genome
      and several complete proviral genomes were retrieved. Some copies contained full
      open reading frames for all viral components. The lack of a complete genome in
      the other Lagomorph species did not allow further analyses of the provirus,
      although more deleterious mutations were found in Bunolagus and Pentalagus than
      in Oryctolagus RNaseH-amplified sequences. To what extent RERV-H and other
      endogenous viruses might have had an impact on the rabbit genome and its immune
      system remains elusive.

PMID- 29208425
TI  - Serum uric acid as a potential marker for heart failure risk in men on
      antihypertensive treatment: The British Regional Heart Study.
AB  - The role of serum uric acid (SUA) as a prognostic marker for incident heart
      failure (HF) in hypertensive subjects is uncertain. We have prospectively
      examined the relationship between SUA and incident HF in 3440 men aged 60-79years
      separately in those on and not on antihypertensive treatment who were followed up
      for a mean period of 15years. Men on SUA lowering drugs and those with history of
      HF or myocardial infarction were excluded. There were 260 incident HF cases. The
      men were divided into three groups of SUA concentrations/levels (<350, 350-410
      and >410MUmol/L). Raised SUA was associated with significantly increased risk of
      HF in men on antihypertensive treatment (N=949) but not in those without (N=2491)
      (p=0.003 for interaction). In men on antihypertensive treatment those with
      hyperuricemia (>410MUmol/L) had the most adverse biological risk profile for HF
      including the highest rates of atrial fibrillation and renal dysfunction and the
      highest mean level of BMI, c-reactive protein and cardiac function (cardiac
      troponin T). Treated hypertensive men with SUA levels>410MUmol/L showed an
      increase in risk of HF of more than twofold compared to those on treatment with
      levels <350MUmol/L even after adjustment for lifestyle characteristics and
      biological risk factors [adjusted hazard ratio 2.26 (1.23,4.15)]. SUA improved
      prediction of HF beyond routine conventional risk factors (p=0.02 for improvement
      in c-statistics). SUA as a marker of increased xanthine oxidase activity may be a
      useful prognostic marker for HF risk in older men on antihypertensive treatment.

PMID- 29208427
TI  - Clinical decision making: more than just an algorithm.

PMID- 29208426
TI  - 5-Azacytidine engages an IRE1alpha-EGFR-ERK1/2 signaling pathway that stabilizes
      the LDL receptor mRNA.
AB  - Hepatic low-density lipoprotein receptor (LDLR) is the primary conduit for the
      clearance of plasma LDL-cholesterol and increasing its expression represents a
      central goal for treating cardiovascular disease. However, LDLR mRNA is unstable
      and undergoes rapid turnover mainly due to the three AU-rich elements (ARE) in
      its proximal 3'-untranslated region (3'-UTR). Herein, our data revealed that 5
      azacytidine (5-AzaC), an antimetabolite used in the treatment of myelodysplastic
      syndrome, stabilizes the LDLR mRNA through a previously unrecognized signaling
      pathway resulting in a strong increase of its protein level in human hepatocytes
      in culture. 5-AzaC caused a sustained activation of the inositol-requiring enzyme
      1alpha (IRE1alpha) kinase domain and c-Jun N-terminal kinase (JNK) independently
      of endoplasmic reticulum stress. This resulted in activation of the epidermal
      growth factor receptor (EGFR) and extracellular signal-regulated kinase1/2
      (ERK1/2) that, in turn, stabilized LDLR mRNA. Systematic mutation of the AREs
      (ARE1-3) in the LDLR 3'UTR and expression of each mutant coupled to a luciferase
      reporter in Huh7 cells demonstrated that ARE1 is required for rapid LDLR mRNA
      decay and 5-AzaC-induced mRNA stabilization via the IRE1alpha-EGFR-ERK1/2
      signaling cascade. The characterization of this pathway will help to reveal
      potential targets to enhance plasma LDL clearance and novel cholesterol-lowering
      therapeutic strategies.

PMID- 29208428
TI  - Lung cancer in Asian women and health system implications for Australia.

PMID- 29208429
TI  - Checkpoint inhibitors and aspergillosis in AML: the double hit hypothesis.

PMID- 29208430
TI  - Make Blood Cancer Visible.

PMID- 29208431
TI  - Cancer in two Renaissance families.

PMID- 29208432
TI  - Go, no-go decision making for phase 3 clinical trials: ACT IV revisited.

PMID- 29208434
TI  - Correction to Lancet Oncol 2017; 18: 1555-56.

PMID- 29208433
TI  - Go, no-go decision making for phase 3 clinical trials: ACT IV revisited -
      Authors' reply.

PMID- 29208435
TI  - Correction to Lancet Oncol 2017; 18: 1493-1501.

PMID- 29208436
TI  - Correction to Lancet Oncol 2016; 17: 1637-38.

PMID- 29208437
TI  - Correction to Lancet Oncol 2017; 18: 1061-75.

PMID- 29208438
TI  - An integrated multidisciplinary algorithm for the management of spinal
      metastases: an International Spine Oncology Consortium report.
AB  - Spinal metastases are becoming increasingly common because patients with
      metastatic disease are living longer. The close proximity of the spinal cord to
      the vertebral column limits many conventional therapeutic options that can
      otherwise be used to treat cancer. In response to this problem, an innovative
      multidisciplinary approach has been developed for the management of spinal
      metastases, leveraging the capabilities of image-guided stereotactic
      radiosurgery, separation surgery, vertebroplasty, and minimally invasive local
      ablative approaches. In this Review, we discuss the variables that should be
      considered during the management of these patients and review the role of each
      discipline and their respective management options to provide optimal care. This
      work is synthesised into a practical algorithm to aid clinicians in the
      management of patients with spinal metastasis.

PMID- 29208439
TI  - De-novo and acquired resistance to immune checkpoint targeting.
AB  - Use of immune checkpoint inhibitors targeting the programmed cell death protein
      1/programmed cell death-ligand 1 and cytotoxic T lymphocyte-associated protein-4
      axes has yielded impressive results in some clinical trials. However, only a
      subset of patients initially respond to these inhibitors, and increasing clinical
      evidence indicates that a substantial proportion of initial responders ultimately
      relapse with lethal, drug-resistant disease months or years later. Studies that
      have used massively parallel sequencing have shed light on the rich functional
      landscape of mutations that endow tumour cells with the ability to evade T-cell
      mediated immunosurveillance. Cancer genomes bear signatures of clonal evolution
      and selection, particularly implicating acquired defects in interferon receptor
      signalling and antigen presentation. In this Review, we discuss the biological
      processes that operate in the formation of so-called immunoresistant niches, and
      describe the latest progress in the development of combination strategies to
      reinstate immunosurveillance in immune-refractory tumours.

PMID- 29208440
TI  - Radiotherapy in the setting of breast reconstruction: types, techniques, and
      timing.
AB  - As the use of breast reconstruction and postmastectomy radiotherapy (PMRT) has
      increased over the past decade, the typical approach to integrating radiotherapy
      with breast reconstruction has provoked intense controversy in the management of
      breast cancer. PMRT can lead to an increased frequency of complications in the
      reconstructed breast. Conversely, the reconstructed breast can increase the
      complexity of radiotherapy delivery. How to minimise the frequency of
      complications without compromising oncological or cosmetic outcomes of the
      reconstructed breast is an important shared multidisciplinary goal for
      oncologists and their patients. Several questions remain, however, regarding the
      type of reconstruction that should be used with PMRT, when reconstruction should
      be done relative to PMRT and whether radiotherapy treatment should be directed
      towards the tissue expander or the implant for women who opt for a two-stage
      expander-implant reconstruction. Following advances in the planning of
      radiotherapy treatment, new questions about the application of these technologies
      in the setting of breast reconstruction have arisen. In this Review, we address
      these questions by reviewing contemporary evidence on the optimal integration of
      radiotherapy and breast reconstruction in the management of breast cancer.

PMID- 29208441
TI  - European position statement on lung cancer screening.
AB  - Lung cancer screening with low-dose CT can save lives. This European Union (EU)
      position statement presents the available evidence and the major issues that need
      to be addressed to ensure the successful implementation of low-dose CT lung
      cancer screening in Europe. This statement identified specific actions required
      by the European lung cancer screening community to adopt before the
      implementation of low-dose CT lung cancer screening. This position statement
      recommends the following actions: a risk stratification approach should be used
      for future lung cancer low-dose CT programmes; that individuals who enter
      screening programmes should be provided with information on the benefits and
      harms of screening, and smoking cessation should be offered to all current
      smokers; that management of detected solid nodules should use semi-automatically
      measured volume and volume-doubling time; that national quality assurance boards
      should be set up to oversee technical standards; that a lung nodule management
      pathway should be established and incorporated into clinical practice with a
      tailored screening approach; that non-calcified baseline lung nodules greater
      than 300 mm3, and new lung nodules greater than 200 mm3, should be managed in
      multidisciplinary teams according to this EU position statement recommendations
      to ensure that patients receive the most appropriate treatment; and planning for
      implementation of low-dose CT screening should start throughout Europe as soon as
      possible. European countries need to set a timeline for implementing lung cancer
      screening.

PMID- 29208442
TI  - Defining a global research and policy agenda for betel quid and areca nut.
AB  - Betel quid and areca nut are known risk factors for many oral and oesophageal
      cancers, and their use is highly prevalent in the Asia-Pacific region.
      Additionally, betel quid and areca nut are associated with health effects on the
      cardiovascular, nervous, gastrointestinal, metabolic, respiratory, and
      reproductive systems. Unlike tobacco, for which the WHO Framework Convention on
      Tobacco Control provides evidence-based policies for reducing tobacco use, no
      global policy exists for the control of betel quid and areca nut use.
      Multidisciplinary research is needed to address this neglected global public
      health emergency and to mobilise efforts to control betel quid and areca nut use.
      In addition, future research is needed to advance our understanding of the basic
      biology, mechanisms, and epidemiology of betel quid and areca nut use, to advance
      possible prevention and cessation programmes for betel quid and areca nut users,
      and to design evidence-based screening and early diagnosis programmes to address
      the growing burden of cancers that are associated with use.

PMID- 29208443
TI  - A polymorphous bullous dermatosis.

PMID- 29208444
TI  - Characterization of outer membrane vesicles of Acetobacter pasteurianus NBRC3283.
AB  - Acetobacter pasteurianus is characterized as a fermenting bacterium of kurozu,
      which is a common traditional Japanese black vinegar. Recently, we separated acid
      resistant and low Toll-like receptor 4 (TLR4)-stimulatory lipopolysaccharides
      (LPS) from A. pasteurianus. We also showed that their lipid A parts possessed a
      novel sugar backbone that is responsible for the low TLR4-stimulatory and acid
      resistant properties of the LPS. Outer membrane vesicles (OMVs) are nano-sized
      spherical structures secreted from many gram-negative bacteria. OMVs contain LPS
      and act as immunomodulants such as vaccines. In this study, we investigated OMVs
      secreted from A. pasteurianus. OMV secretion from A. pasteurianus NBRC 3283 cells
      was observed after 2 days in culture by transmission electron microscopy imaging.
      Thus OMVs were separated from the culture supernatants by ultracentrifugation and
      then purified by OptiPrep density gradient centrifugation. The OMVs contained
      several proteins including outer membrane proteins, and several sugars as
      components of LPS. The OMVs weakly stimulated TLR4 in accordance with the
      activity of A. pasteurianus LPS. Additionally, the TLR2-stimulating activity of
      the OMVs was significantly potent, indicating the existence of lipoproteins.
      Furthermore OMV-like spherical particles were observed in kurozu. Some of these
      particles are probably derived from A. pasteurianus. These data suggest that A.
      pasteurianus produce OMVs that contain LPS and probably lipoproteins, and can
      modulate the innate immune system.

PMID- 29208445
TI  - Optimal Interval for 18F-FDG-PET After Chemoradiotherapy for Rectal Cancer.
AB  - INTRODUCTION: Although 18F-fluorodeoxyglucose (FDG)-positron emission tomography
      (PET) has been increasingly used to evaluate the response to preoperative
      chemoradiotherapy (CRT) in patients with rectal cancer, the optimal intervals
      between completion of CRT, PET, and surgery have not been fully investigated.
      PATIENTS AND METHODS: A total of 148 consecutive patients with rectal
      adenocarcinoma who received CRT followed by FDG-PET and radical surgery were
      retrospectively analyzed. The association between the FDG-PET maximum
      standardized uptake value (SUVmax) and pathological response was assessed using a
      logistic regression model, with a primary focus on the intervals between CRT and
      PET as well as between PET and surgery. RESULTS: The baseline SUVmax showed no
      association with pathological response (P = .201; area under the curve [AUC] =
      0.528), whereas the SUVmax after CRT completion showed a strong association (P <
      .001; AUC = 0.707). Logistic regression analysis revealed that the ability of the
      SUVmax to accurately predict pathological good responders was significantly
      associated with a long CRT-PET interval (>= 7 weeks; P = .027), but was not
      affected by the length of PET-surgery interval. In patients with a short CRT-PET
      interval (< 7 weeks), the ability of the SUVmax to predict good responders was
      poor (P = .201; AUC = 0.669); however, in patients with long intervals (>= 7
      weeks), the predictive ability markedly improved (P < .001; AUC = 0.879).
      CONCLUSION: A minimum wait time of 7 weeks is recommended before performing FDG
      PET after neoadjuvant CRT for rectal cancer to obtain maximal predictive accuracy
      for pathological response.

PMID- 29208446
TI  - Person-Centered Care Planning: Preferences Are a Priority.

PMID- 29208447
TI  - Impact of Advanced Practice Registered Nurses on Quality Measures: The Missouri
      Quality Initiative Experience.
AB  - PURPOSE: The purpose of this article is to review the impact of advanced practice
      registered nurses (APRNs) on the quality measure (QM) scores of the 16
      participating nursing homes of the Missouri Quality Initiative (MOQI)
      intervention. The MOQI was one of 7 program sites in the US, with specific
      interventions unique to each site tested for the Centers for Medicaid and
      Medicare Services Innovations Center. While the goals of the MOQI for long-stay
      nursing home residents did not specifically include improvement of the QM scores,
      it was anticipated that improvement most likely would occur. Primary goals of the
      MOQI were to reduce the frequency of avoidable hospital admissions and
      readmissions; improve resident health outcomes; improve the process of
      transitioning between inpatient hospitals and nursing facilities; and reduce
      overall healthcare spending without restricting access to care or choice of
      providers. METHODS: A 2-group comparison analysis was conducted using statewide
      QMs; a matched comparison group was selected from facilities in the same counties
      as the intervention homes, similar baseline QM scores, similar size and
      ownership. MOQI nursing homes each had an APRN embedded full-time to improve care
      and help the facility achieve MOQI goals. Part of their clinical work with
      residents and staff was to focus on quality improvement strategies with potential
      to influence healthcare outcomes. Trajectories of QM scores for the MOQI
      intervention nursing homes and matched comparison group homes were tested with
      nonparametric tests to examine for change in the desired direction between the 2
      groups from baseline to 36 months. A composite QM score for each facility was
      constructed, and baseline to 36-month average change scores were examined using
      nonparametric tests. Then, adjusting for baseline, a repeated measures analysis
      using analysis of covariance as conducted. RESULTS: Composite QM scores of the
      APRN intervention group were significantly better (P = .025) than the comparison
      group. The repeated measures analysis identified statistically significant group
      by time interaction (P = .012). Then group comparisons were made at each of the 6
      month intervals and statistically significant differences were found at 24 months
      (P = .042) and 36 months (P = .002), and nearly significant at 30 months (P =
      .11). IMPLICATIONS: APRNs working full time in nursing homes can positively
      influence quality of care, and their impact can be measured on improving QMs. As
      more emphasis is placed on quality and outcomes for nursing home services,
      providers need to find successful strategies to improve their QMs. Results of
      these analyses reveal the positive impact on QM outcomes for the majority of the
      MOQI nursing homes, indicating budgeting for APRN services can be a successful
      strategy.

PMID- 29208448
TI  - Investigation of TGFbetaR2 SNP rs4522809, Osteopontin, TGF beta1 and their
      association with dilatative pathology of ascending thoracic aorta.
AB  - BACKGROUND: Dilatative pathology of the ascending thoracic aorta (DPATA) is
      characterized by the aortic wall expansion more than 1.5 and could be accompanied
      by aortic wall rupture. Mutations of TGFBR2 gene demonstrated an association with
      syndromic DPATA and altered pathway of transforming growth factor beta (TGF
      beta). Elevated TGF-beta1 level has been found in blood samples in DPATA group.
      Moreover, elevated osteopontin (OPN) level was associated with mutations of
      TGFBR2 gene. Based on recently published findings, we aimed to evaluate
      genotyping results of TGFBR2 rs4522809 and the association with circulating OPN
      and TGF-beta1 concentrations within DPATA patients. METHODS AND FINDINGS: TGFBR2
      SNP genotyping assay was performed by quantitative real-time PCR, TGF-beta1 and
      OPN concentrations were measured using enzyme-linked immunosorbent assay.
      Genotyping results showed G allele to be associated with DPATA (p = .01), the
      presence of G allele significantly increased the possibility of DPATA by 1.67
      times (OR = 1.67, 95%, CI = 1.12-2.47). TGF-beta1 concentration was significantly
      higher in DPATA subjects compared with Reference group (p = 0,001). Finally, we
      found moderate inverse correlation (r = -0,524) between circulating TGF-beta1 and
      OPN levels within DPATA subjects (p = 0,002), as increasing levels of TGF-beta1
      cytokine significantly decrease concentration of OPN. CONCLUSIONS: This is the
      first report on the association between previously defined TGFbetaR2 SNP
      rs4522809 linked with dilatation of ascending thoracic aorta. Also, for the first
      time we report the inversed correlation between circulating TGF-beta1 and OPN
      concentrations in DPATA subjects indicating the possible biomarkers for DPATA.

PMID- 29208450
TI  - Intracameral Chemotherapy for Globe Salvage in Retinoblastoma with Secondary
      Anterior Chamber Invasion.

PMID- 29208449
TI  - Surgical Treatment of Thoracic Spinal Tuberculosis: A Multicenter Retrospective
      Study.
AB  - OBJECTIVE: The aim of the present multicenter, retrospective study was to assess
      the safety and effectiveness of different surgery strategies for the treatment of
      thoracic tuberculosis and to provide a reference for surgical treatment of
      thoracic tuberculosis. MATERIALS AND METHODS: This study reviewed 394 patients
      with thoracic tuberculosis who were treated in 6 institutions between January
      2000 and January 2015. There were 208 men and 186 women with an average age of
      34.92 +/- 13.14 years (range 5-76 years). A total of 73 patients underwent one
      stage anterior surgery (group A); 84 underwent an anterior combined posterior
      surgery (group B); and 237 underwent one-stage posterior surgery (group C).
      Clinical outcome, laboratory indexes, and radiologic results were analyzed to
      observe the advantage of posterior approach surgery. RESULTS: All cases were
      followed up for about 26-60 months (average of 37 months). At the last follow-up,
      all patients reached bone fusion, pain relief, and neurologic recovery. There
      were significant differences before and after treatment in terms of the visual
      analog scale and Oswestry Disability Index scores (P < 0.05). Posterior approach
      significantly improved kyphosis (P < 0.05). CONCLUSIONS: Posterior fixation is
      superior to anterior fixation in the correction of kyphosis and maintenance of
      spinal stability. One-stage posterior surgery can achieve the same efficacy as
      anterior-only or combined surgery, with less trauma, less blood loss, and shorter
      operative times. However, for wide lesions or paraspinal abscesses, severe bone
      destruction, and anterior and middle column defects that are too large after
      debridement to require long segment bone grafting, the anterior combined
      posterior approach is indispensable.

PMID- 29208451
TI  - [Influence of occupation on cognitive impairment with no dementia in a sample
      population over 55 years from Zaragoza].
AB  - INTRODUCTION: The prevalence of cognitive impairment with no dementia (CIND)
      varies between 5.1% and 35.9%, increasing between 65 and 85 years. The CIND
      increases the risk of dementia. Factors such as education, occupation, and social
      activities are associated with the risk of cognitive impairment. The main
      objective of this study was to analyse the association between the main
      occupation developed throughout life and CIND in a general population sample of
      over 55 years. METHODS: In wave I of the ZARADEMP Project, a sample (n=4803) of
      people over 55 years was interviewed. CIND measurement was obtained through the
      Mini Mental State Examination. Occupational activity data were recoded into white
      collar, blue collar, homemakers, and farmers. The association between the
      occupation variables and CIND was estimated using the odds ratio, and 95%
      confidence intervals using logistic regression equations. RESULTS: The prevalence
      of CIND in the sample was 28.2%. As regards white collar workers, the CIND
      diagnosis odds was 53% higher for blue collar workers, 77% higher for women who
      were homemakers and almost twice for farmers, after controlling for socio
      demographic, behavioural and clinical variables. All results were statistically
      significant. CONCLUSIONS: CIND frequency is influenced by the previous occupation
      of the subjects. An occupation with higher intellectual requirements can help
      keep cognitive functions intact for longer.

PMID- 29208452
TI  - External validation of mortality prognostic indices after hospital discharge in
      older adults.

PMID- 29208453
TI  - Comparison of survival between hemodialysis and peritoneal dialysis patients with
      end-stage renal disease in the era of icodextrin treatment.
AB  - BACKGROUND: Icodextrin could reduce the risk of technique failure and improve
      patient survival in peritoneal dialysis (PD) patients. This study compared the
      survival between incident hemodialysis (HD) and PD patients, with and without
      diabetes, in the era of icodextrin treatment. METHODS: From the Taiwan health
      insurance database, 53,103 incident end-stage renal disease patients undergoing
      dialysis were identified from 2005 to 2010. The mortality risks among HD and PD
      patients with or without icodextrin treatment were compared. The follow-up period
      started from the date of dialysis initiation to December 31, 2011. The competing
      risks regression model was used to estimate the subhazard ratio (SHR) of death
      with considering renal transplantation as a competing event. RESULTS: Compared
      with the corresponding HD patients, mortality risks were higher in diabetic PD
      patients with icodextrin treatment (Bonferroni adjusted SHR=1.16, 98.3% CI=1.04
      1.30) and without the treatment (Bonferroni adjusted SHR=1.35, 98.3% CI=1.16
      1.57), particularly for elderly patients. Mortality risks for patients without
      diabetes were not different among the three cohorts. The time-dependent competing
      risks model showed that PD patients with icodextrin treatment exhibited a reduced
      risk of death for diabetic patients, compared with those without icodextrin
      treatment (adjusted SHR=0.84, 95% CI=0.72-0.97). CONCLUSIONS: Icodextrin could
      attenuate the survival disadvantage for PD relative to HD in diabetic patients,
      particularly for the elderly patients.

PMID- 29208454
TI  - Pope Francis and the end-of-life: Time for serious reflection.

PMID- 29208455
TI  - High prevalence and incidence of HPV-related anal cancer precursor lesions in HIV
      positive women in the late HAART era.
AB  - INTRODUCTION: Anal cancer is one of the most common non-AIDS defining
      malignancies, especially in men who have sex with men and women living with HIV
      (WLHIV). OBJECTIVES: To evaluate the prevalence and incidence of precursor
      lesions (high-grade squamous intraepithelial lesions [HSIL]) and anal cancer in
      our cohort of women and to compare them to cervical lesions; to calculate the
      percentage of patients that acquire and clear oncogenic genotypes (HR-HPV) in the
      anal canal; and to determine predictive factors for anal HPV infection. PATIENTS
      AND METHODS: Prospective-longitudinal study (May 2012-December 2016). At baseline
      (V1) and follow up visits, anal mucosa samples were taken in liquid medium for
      cytology and HPV PCR. In cases of abnormal anal cytology and/or positive HR-HPV
      PCR results, a high resolution anoscopy was performed. Patients were also
      referred to the gynaecologist. RESULTS: Ninety five women with an average age of
      43.7years were included. At baseline, 11.6% had cervical abnormalities (4.1%
      CIN1, 2.2% CIN2/3, 1.1% cervical cancer), 64.3% anal abnormalities (50%
      LSIL/AIN1, 9.5% HSIL/AIN2/3 and 2.4% anal cancer) and 49.4% had HR-HPV genotypes.
      During 36months of follow up, the incidence of anal HSIL was 16*1,000 person
      years; 14.8% acquired HR-HPV genotypes and 51.2% cleared them, P=.007. No
      patients presented CIN1/2/3/ or cervical cancer. In the multivariate analysis we
      found the following predictive factors for HR-HPV infection: smoking (RR: 1.55,
      95%CI: 0.99-2.42), number of sexual partners >3 (RR: 1.69; 95%CI: 1.09-2.62),
      cervical and anal dysplasia (RR: 1.83; 95%CI: 1.26-2.67) and (RR: 1.55; 95%CI:
      1.021-2.35), respectively. CONCLUSIONS: Despite clearance rates of anal oncogenic
      genotypes being higher than acquisition rates, prevalence and incidence of HSIL
      were still high and greater than cervical HSIL. Therefore, screening for these
      lesions should perhaps be offered to all WLHIV.

PMID- 29208456
TI  - Human immunodeficiency virus screening: Is it appropriate in hospital emergency
      departments?

PMID- 29208457
TI  - How, when and whom, selective screening of HIV at the emergency department.

PMID- 29208458
TI  - Inhibition of TGF-beta pathway reverts extracellular matrix remodeling in T.
      cruzi-infected cardiac spheroids.
AB  - Chagasic cardiomyopathy (CC) is the main manifestation of Chagas Disease (CD). CC
      is a progressive dysfunctional illness, in which transforming growth factor beta
      (TGF-beta) plays a central role in fibrogenesis and hypertrophy. In the present
      study, we tested in a three-dimensional (3D) model of cardiac cells culture
      (named cardiac spheroids), capable of mimicking the aspects of fibrosis and
      hypertrophy observed in CC, the role of TGF-beta pathway inhibition in restoring
      extracellular matrix (ECM) balance disrupted by T. cruzi infection. Treatment of
      T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF
      beta type I receptor, resulted in a reduction in the size of spheroids, which was
      accompanied by a decrease in parasite load and in fibronectin expression. The
      inhibition of TGF-beta pathway also promoted an increase in the activity of
      matrix metalloproteinase (MMP)-2 and a decrease in tissue inhibitor of matrix
      metalloproteinase (TIMP)-1 expression, which may be one of the mechanisms
      regulating extracellular matrix remodeling. Therefore, our study provides new
      insights into the molecular mechanisms by which inhibition of TGF-beta signaling
      reverts fibrosis and hypertrophy generated by T. cruzi during CC and also
      highlights the use of cardiac spheroids as a valuable tool for the study of
      fibrogenesis and anti-fibrotic compounds.

PMID- 29208459
TI  - MiR-3202 protects smokers from chronic obstructive pulmonary disease through
      inhibiting FAIM2: An in vivo and in vitro study.
AB  - Previous study found the variable miR-3202 as a potential biomarker in smoker
      with or without chronic obstructive pulmonary disease (COPD). This study aims to
      identify the molecular involvement of miR-3202 in the pathophysiology of COPD.
      Level of miR-3202 in blood sample of non-smoker non-COPD(C), smoker without
      COPD(S), smoker with stable COPD(S-COPD) and smoker with acute exacerbation
      COPD(AE-COPD) was observed by quantitative real-time PCR. By bioinformatics
      prediction, Fas apoptotic inhibitory molecule 2 (FAIM2) was identified as a
      potential target of miR-3202. In vitro, human bronchial epithelial (HBE) cells
      and cigarette smoke extract (CSE) stimulated T lymphocytes were co-cultured. Cell
      proliferation and apoptosis of HBE cells were determinated. In vivo, rats were
      exposed in cigarette smoke for 30 days and expression of miR-3202 and FAIM2 in
      bronchia were detected. Results showed that The miR-3202 was down-regulated in S,
      S-COPD and AE-COPD group when compared with C group. Decreased level of miR-3202
      was also observed in CSE treated T lymphocyte. Additionally, CSE stimulation
      increased INF-gamma and TNF-alpha levels and FAIM2 expression whereas inhibited
      Fas and FasL expressions in T lymphocytes. However, these effects were
      significantly suppressed by miR-3202 overexpression and enhanced by miR-3202
      inhibitor. Likely to exogenous miR-3202, FAIM2 knockdown significantly inhibited
      HBE cells apoptosis, as well as inhibited INF-gamma and TNF-alpha levels. In COPD
      rats model, miR-3202 was reduced while FAIM2 was up-regulated accordingly. Here,
      results suggest that high level miR-3202 in T lymphocytes may protect epithelial
      cells through targeting FAIM2. MiR-3202 might be used as a notable biomarker of
      COPD.

PMID- 29208460
TI  - RalGPS2 is involved in tunneling nanotubes formation in 5637 bladder cancer
      cells.
AB  - RalGPS2 is a Ras-independent Guanine Nucleotide Exchange Factor (GEF) for RalA
      containing a PH domain and an SH3-binding region and it is involved in several
      cellular processes, such as cytokinesis, control of cell cycle progression,
      differentiation, cytoskeleton organization and rearrangement. Up to now, few data
      have been published regarding RalGPS2 role in cancer cells, and its involvement
      in bladder cancer is yet to be established. In this paper we demonstrated that
      RalGPS2 is expressed in urothelial carcinoma-derived 5637 cancer cells and is
      essential for cellular growth. These cells produces thin membrane protrusions
      that displayed the characteristics of actin rich tunneling nanotubes (TNTs) and
      here we show that RalGPS2 is involved in the formation of these cellular
      protrusions. In fact the overexpression of RalGPS2 or of its PH-domain increased
      markedly the number and the length of nanotubes, while the knock-down of RalGPS2
      caused a strong reduction of these structures. Moreover, using a series of RalA
      mutants impaired in the interaction with different downstream components (Sec5,
      Exo84, RalBP1) we demonstrated that the interaction of RalA with Sec5 is required
      for TNTs formation. Furthermore, we found that RalGPS2 interacts with the
      transmembrane MHC class III protein leukocyte specific transcript 1 (LST1) and
      RalA, leading to the formation of a complex which promotes TNTs generation. These
      findings allow us to add novel elements to molecular models that have been
      previously proposed regarding TNTs formation.

PMID- 29208461
TI  - Simvastatin inhibits the development of radioresistant esophageal cancer cells by
      increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT
      pathway.
AB  - Acquired radioresistance compromises the efficacy of radiotherapy for carcinomas
      including esophageal cancer (EC), thus resulting in recurrence and poor survival.
      Recent research corroborated radiosensitive function of simvastatin in stem-like
      breast cancer cells. However, its role in EC radioresistance remains poorly
      elucidated. Here, we developed a radioresistant EC cell line Ec9706-R with higher
      resistance to irradiation relative to control Ec9706 cells. Intriguingly, Ec9706
      R cells exhibited epithelial-mesenchymal transition (EMT) characteristics with
      high invasion and migration ability. Simvastatin sensitized radioresistance of
      Ec9706-R cells and suppressed cell proliferation, but aggravated radiation
      induced apoptosis and caspase-3 activity. Furthermore, simvastatin reversed EMT
      and inhibited cell invasion and migration of Ec9706-R cells. Mechanism assay
      confirmed the activation of PI3K/AKT pathway after radiation, which was inhibited
      by simvastatin. After restoring this pathway by its activator, IGF-1, simvastatin
      mediated radiosensitivity and EMT reversion were abrogated. Further assay
      substantiated the PTEN suppression after irradiation, which was elevated
      following simvastatin pre-treatment. Moreover, PTEN cessation attenuated the
      inhibitory effect of simvastatin on PI3K/AKT activation, and subsequently
      antagonized simvastatin-induced radiosensitivity and EMT reversion. Additionally,
      simvastatin aggravated radiation-mediated Ec9706-R tumor growth inhibition.
      Together, simvastatin inhibits the development of Ec9706-R cells by increasing
      radiosensitivity and reversing EMT via PTEN-PI3K/AKT pathway, implying a
      promising strategy against EC radioresistance.

PMID- 29208462
TI  - MicroRNA-630 inhibits breast cancer progression by directly targeting BMI1.
AB  - MicroRNAs (miRNAs) play critical roles in breast cancer cell biological
      processes, including proliferation and apoptosis by inhibiting the expression of
      their target genes. Herein, we reported that miR-630 overexpression initiates
      apoptosis, blocks cell cycle progression and suppresses cell proliferation in
      breast cancer cells. Furthermore, BMI1, a member of polycomb group family, was
      identified as a direct target of miR-630, and there was a negative correlation
      between the expression levels of BMI1 and miR-630 in human breast cancer samples.
      With a series of biology approaches, subsequently, we proved that BMI1 was a
      functional downstream target of miR-630 and mediated the property of miR-630
      dependent inhibition of breast cancer progression. Taken together, these findings
      provide further evidence on the tumor-suppression function of miR-630 in breast
      cancer, and clarify BMI1 as a novel functional target gene of miR-630.

PMID- 29208463
TI  - Stellate ganglion block ameliorates vascular calcification by inhibiting
      endoplasmic reticulum stress.
AB  - AIMS: Vascular calcification (VC) underlies substantial cardiovascular morbidity
      and mortality. No clinically therapies have emerged presently. Stellate ganglion
      block (SGB) is one of the most often used sympathetic blockade procedure, and
      regulates vascular dilation. However, the effect of SGB on VC is still unknown.
      Therefore, we aimed to identify the ameliorative effect of SGB on VC. KEY
      FINDING: In vivo VC was induced in rats by administering vitamin D3 plus nicotine
      (VDN), and in vitro calcification of rat aortic vascular smooth muscle cells
      (VSMC) was induced by beta-glycerophosphate. In VDN rats, alkaline phosphatase
      (ALP) activity and Calcium contents were higher than that in control rats. The
      transformation of VSMC from contractile to osteoblast-like phenotype was observed
      in calcified aorta. SGB ameliorated the increase of ALP activity and Calcium
      content, and the transformation of VSMC in calcified aorta. The stimulation of
      endoplasmic reticulum stress (ERS) in calcified aorta was also attenuated by SGB
      treatment. The inducer of ERS, tunicamycin could block the beneficial effect of
      SGB on VC, and the ERS inhibitor, 4-PBA could mimic the amelioration of SGB.
      Furthermore, SGB attenuated the increased plasma levels of norepinephrine in VDN
      rats. In vitro experiments, norepinephrine exaggerated VSMC calcification,
      phenotype transformation and ERS. SIGNIFICANCE: These results demonstrate that
      SGB could inhibit sympathetic nervous activity, and then prevent the activation
      of ERS followed by ameliorating VC. Sympathetic over-activation might play
      critical role in the pathogenesis of VC, which provides new strategy and target
      for therapy and prevention of VC.

PMID- 29208465
TI  - A curvature-dependent membrane binding by tyrosine kinase Fer involves an
      intrinsically disordered region.
AB  - Tyrosine kinases are important enzymes that mediate signal transduction at the
      plasma membrane. While the significance of membrane localization of tyrosine
      kinases has been well evaluated, the role of membrane curvature in their
      regulation is unknown. Here, we demonstrate that an intrinsically disordered
      region in the tyrosine kinase Fer acts as a membrane curvature sensor that
      preferentially binds to highly curved membranes in vitro. This region forms an
      amphipathic alpha-helix upon interaction with curved membranes, aligning
      hydrophobic residues on one side of the helical structure. Further, the tyrosine
      kinase activity of Fer is significantly enhanced by the membrane in a manner
      dependent on curvature. We propose a model for the regulation of Fer based on an
      intramolecular interaction and the curvature-dependent membrane binding mediated
      by its intrinsically disordered region.

PMID- 29208464
TI  - Risk factors for postpolypectomy bleeding in patients receiving anticoagulation
      or antiplatelet medications.
AB  - BACKGROUND AND AIMS: Balancing the risks for thromboembolism and postpolypectomy
      bleeding in patients requiring anticoagulation and antiplatelet agents is
      challenging. We investigated the incidence and risk factors for postpolypectomy
      bleeding on anticoagulation, including heparin bridge and other antithrombotic
      therapy. METHODS: We performed a retrospective cohort and case control study at 2
      tertiary-care medical centers from 2004 to 2012. Cases included male patients on
      antithrombotics with hematochezia after polypectomy. Nonbleeding controls were
      matched to cases 3 to 1 by antithrombotic type, study site, polypectomy
      technique, and year of procedure. Our outcomes were the incidence and risk
      factors for postpolypectomy bleeding. RESULTS: There were 59 cases and 174
      matched controls. Postpolypectomy bleeding occurred in 14.9% on bridge
      anticoagulation. This was significantly higher than the overall incidence of
      bleeding on antithrombotics at 1.19% (95% confidence interval, 0.91%-1.54%)
      (59/4923). We identified similarly low rates of bleeding in patients taking
      warfarin (0.66%), clopidogrel (0.84%), and aspirin (0.92%). Patients who bled
      tended to have larger polyps (13.9 vs 7.3 mm; P < .001) and more polyps >=2 cm
      (41% vs 10%; P < .001). Bleeding risk was increased with restarting
      antithrombotics within 1 week postpolypectomy (odds ratio [OR] 4.50; P < .001),
      having polyps >=2 cm (OR 5.94; P < .001), performing right-sided cautery (OR
      2.61; P = .004), and having multiple large polyps (OR 2.92; P = .001). Among
      patients on warfarin, the presence of bridge anticoagulation was an independent
      risk factor for postpolypectomy bleeding (OR 12.27; P = .0001). CONCLUSION: We
      conclude that bridge anticoagulation is associated with a high incidence of
      postpolypectomy bleeding and is an independent risk factor for hemorrhage
      compared with patients taking warfarin alone. A higher threshold to use bridge
      anticoagulation should be considered in patients with an elevated bleeding risk.

PMID- 29208467
TI  - Human proton coupled folic acid transporter is a monodisperse oligomer in the
      lauryl maltose neopentyl glycol solubilized state.
AB  - The human proton coupled folic acid transporter PCFT is the major import route
      for dietary folates. Mutations in the gene encoding PCFT cause hereditary folic
      acid malabsorption, which manifests itself by compromised folate absorption from
      the intestine and also in impaired folate transport into the central nervous
      system. Since its recent discovery, PCFT has been the subject of numerous
      biochemical studies aiming at understanding its structure and mechanism. One
      major focus has been its oligomeric state, with some reports supporting oligomers
      and others a monomer. Here, we report the overexpression and purification of
      recombinant PCFT. Following detergent screening, n-Dodecyl beta-D-maltoside (DDM)
      and lauryl maltose neopentyl glycol (LMNG) were chosen for further work as they
      exhibited the most optimal solubilization. We found that purified detergent
      solubilized PCFT was able to bind folic acid, thus indicating a functionally
      active protein. Size exclusion chromatography showed that PCFT in DDM was
      polydisperse; the LMNG preparation was clearly monodisperse but with shorter
      retention time than the major DDM peak. To assess the oligomeric state negative
      stain electron microscopy was performed which showed a particle with the size of
      a PCFT dimer.

PMID- 29208466
TI  - Chetomin induces apoptosis in human triple-negative breast cancer cells by
      promoting calcium overload and mitochondrial dysfunction.
AB  - Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive
      to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized
      by Chaetomium cochliodes, has been reported as a promising anticancer and
      antiangiogenic agent but the complete molecular mechanism of its anticancer
      potential remains to be elucidated. In our study, we explored the anti-neoplastic
      action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC
      cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay. It
      exhibited antiproliferative response and induced apoptosis in both the cell
      types. Cell cycle analysis revealed that it increases the sub G0/G1 phase cell
      population. Modulation of mitochondrial membrane potential, activation of caspase
      3/7 and a remarkable increase in the expression of cleaved PARP and increased
      chromatin condensation was observed after CHET treatment in MDA-MB-231 and MDA-MB
      468 cells. Additionally, an elevated level of intracellular Ca2+ played an
      important role in CHET mediated cell death response. Calcium overload in
      mitochondria led to release of cytochrome c which in turn triggered caspase-3
      mediated cell death. Inhibition of calcium signalling using BAPTA-AM reduced
      apoptosis confirming the involvement of calcium signalling in CHET induced cell
      death. Chetomin also inhibited PI3K/mTOR cell survival pathway in human TNBC
      cells. The overall findings suggest that Chetomin inhibited the growth of human
      TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling
      and could be used as a novel chemotherapeutic agent for the treatment of human
      TNBC in future.

PMID- 29208468
TI  - Elevated Markers of Death Receptor-Activated Apoptosis are Associated with
      Increased Risk for Development of Diabetes and Cardiovascular Disease.

PMID- 29208470
TI  - On the statistical analysis of single cell lineage trees.
AB  - Stem cells play a central role in the regeneration and repair of multicellular
      organisms. However, it remains far from trivial to reliably identify them.
      Despite decades of work, current techniques to isolate hematopoietic stem cells
      (HSCs) based on cell-surface markers only result in 50% purity, i.e. half of the
      sorted cells are not stem cells when functionally tested. Modern microscopy
      techniques allow us to follow single cells and their progeny for up to weeks in
      vitro, while recording the cell fates and lifetime of each individual cell. This
      cell tracking generates so-called lineage trees. Here, we propose statistical
      techniques to determine if the initial cell in a lineage tree was a HSC. We apply
      these techniques to murine hematopoietic lineage trees, revealing that 18% of the
      trees in our HSC dataset display a unique signature, and this signature is
      compatible with these trees having started from a true stem cell. Assuming 50%
      purity of HSC empirical datasets, this corresponds to a 0.35 power of the test,
      and the type-1-error is estimated to be 0.047. In summary, this study shows that
      statistical analysis of lineage trees could improve the classification of cells,
      which is currently done based on bio-markers only. Our statistical techniques are
      not limited to mammalian stem cell biology. Any type of single cell lineage
      trees, be it from bacteria, single cell eukaryotes, or single cells in a
      multicellular organism can be investigated. We expect this to contribute to a
      better understanding of the molecules influencing cellular dynamics at the single
      cell level.

PMID- 29208471
TI  - High dietary intake of aromatic amino acids increases risk of hypertension.
AB  - Recent studies investigated the relation between amino acids and blood pressure.
      Our aim was to examine the association between intake of aromatic amino acids
      (AAAs) and risk of hypertension. A total of 4288 individuals, aged 20-70 years,
      participants of the Tehran Lipid and Glucose Study, who were free of hypertension
      at baseline (2008-2011), were followed for 3 years (2011-2014). Average intakes
      of AAAs including phenylalanine, tyrosine, and tryptophan were collected using a
      valid and reliable food frequency questionnaire at baseline. Adjusted logistic
      regression models were used to report odds ratio (OR) of hypertension across
      quartiles of AAAs. At the end of follow-up, 429 (10%) hypertension cases were
      ascertained. The adjusted OR of hypertension for percentage of AAAs from total
      protein intakes was 1.63 (95% confidence interval, 1.06-2.50; P for trend: .03)
      when comparing the highest quartile to the lowest. Furthermore, in the adjusted
      analyses, a statistically significant positive relationship was observed between
      the highest versus the lowest quartile intake of phenylalanine (OR = 1.66; 95%
      confidence interval, 1.14-2.47; P for trend: .03). However, there was no
      significant association of tyrosine and tryptophan intakes with hypertension
      risk. Our data suggest that AAAs may increase the risk of incident hypertension.

PMID- 29208469
TI  - An Elastomeric Polymer Matrix, PEUU-Tac, Delivers Bioactive Tacrolimus
      Transdurally to the CNS in Rat.
AB  - Central nervous system (CNS) neurons fail to regrow injured axons, often
      resulting in permanently lost neurologic function. Tacrolimus is an FDA-approved
      immunosuppressive drug with known neuroprotective and neuroregenerative
      properties in the CNS. However, tacrolimus is typically administered systemically
      and blood levels required to effectively treat CNS injuries can lead to lethal,
      off-target organ toxicity. Thus, delivering tacrolimus locally to CNS tissues may
      provide therapeutic control over tacrolimus levels in CNS tissues while
      minimizing off-target toxicity. Herein we show an electrospun poly(ester
      urethane) urea and tacrolimus elastomeric matrix (PEUU-Tac) can deliver
      tacrolimus trans-durally to CNS tissues. In an acute CNS ischemia model in rat,
      the optic nerve (ON) was clamped for 10s and then PEUU-Tac was used as an ON wrap
      and sutured around the injury site. Tacrolimus was detected in PEUU-Tac wrapped
      ONs at 24h and 14days, without significant increases in tacrolimus blood levels.
      Similar to systemically administered tacrolimus, PEUU-Tac locally decreased glial
      fibrillary acidic protein (GFAP) at the injury site and increased growth
      associated protein-43 (GAP-43) expression in ischemic ONs from the globe to the
      chiasm, consistent with decreased astrogliosis and increased retinal ganglion
      cell (RGC) axon growth signaling pathways. These initial results suggest PEUU-Tac
      is a biocompatible elastic matrix that delivers bioactive tacrolimus trans
      durally to CNS tissues without significantly increasing tacrolimus blood levels
      and off-target toxicity.

PMID- 29208472
TI  - Role of transglutaminase 2 in A1 adenosine receptor- and beta2-adrenoceptor
      mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation
      induced cell death in H9c2 cells.
AB  - Pharmacologically-induced pre- and post-conditioning represent attractive
      therapeutic strategies to reduce ischaemia/reperfusion injury during cardiac
      surgery and following myocardial infarction. We have previously reported that
      transglutaminase 2 (TG2) activity is modulated by the A1 adenosine receptor and
      beta2-adrenoceptor in H9c2 cardiomyoblasts. The primary aim of this study was to
      determine the role of TG2 in A1 adenosine receptor and beta2-adrenoceptor-induced
      pharmacological pre- and post-conditioning in the H9c2 cells. H9c2 cells were
      exposed to 8h hypoxia (1% O2) followed by 18h reoxygenation, after which cell
      viability was assessed by monitoring mitochondrial reduction of MTT, lactate
      dehydrogenase release and caspase-3 activation. N6-cyclopentyladenosine (CPA; A1
      adenosine receptor agonist), formoterol (beta2-adrenoceptor agonist) or
      isoprenaline (non-selective beta-adrenoceptor agonist) were added before
      hypoxia/reoxygenation (pre-conditioning) or at the start of reoxygenation
      following hypoxia (post-conditioning). Pharmacological pre- and post-conditioning
      with CPA and isoprenaline significantly reduced hypoxia/reoxygenation-induced
      cell death. In contrast, formoterol did not elicit protection. Pre-treatment with
      pertussis toxin (Gi/o-protein inhibitor), DPCPX (A1 adenosine receptor
      antagonist) or TG2 inhibitors (Z-DON and R283) attenuated the A1 adenosine
      receptor-induced pharmacological pre- and post-conditioning. Similarly, pertussis
      toxin, ICI 118,551 (beta2-adrenoceptor antagonist) or TG2 inhibition attenuated
      the isoprenaline-induced cell survival. Knockdown of TG2 using small interfering
      RNA (siRNA) attenuated CPA and isoprenaline-induced pharmacological pre- and post
      conditioning. Finally, proteomic analysis following isoprenaline treatment
      identified known (e.g. protein S100-A6) and novel (e.g. adenine
      phosphoribosyltransferase) protein substrates for TG2. These results have shown
      that A1 adenosine receptor and beta2-adrenoceptor-induced protection against
      simulated hypoxia/reoxygenation occurs in a TG2 and Gi/o-protein dependent manner
      in H9c2 cardiomyoblasts.

PMID- 29208473
TI  - Role of beta2- and beta3-adrenoceptors in arterial stiffness in a state of
      hypertension.
AB  - An increase in arterial stiffness is associated with a high risk for morbidity
      and mortality in a state of elevated systemic pressure. The sympathetic nervous
      system plays an important role in the regulation of vascular tone via activation
      of beta-adrenoceptors. The aim of this investigation was to determine the
      involvement of beta-adrenoceptors in the control of arterial stiffness in a state
      of hypertension versus normotension. Pulse wave velocity (PWV), an index of
      vascular stiffness, was assessed in isoflurane-anaesthetized 13-14-week-old male
      spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. At baseline, PWV was
      significantly higher in SH (9.2+/-0.9m/s) compared to WKY rats (6.7+/-0.4m/s).
      The stimulation of beta2- but not beta3-adrenoceptors significantly reduced PWV
      in SH rats despite comparable reductions in blood pressure. Stimulation of beta2-
      or beta3-adrenoceptors did not reduce PWV in WKY rats. The administration of
      sodium nitroprusside (SNP) also significantly reduced PWV in SH but not WKY rats.
      Immunofluorescence revealed the expression of beta2- and beta3-adrenoceptors in
      endothelial cells and vascular smooth muscle cells of the abdominal aorta. There
      were no significant differences in the distribution of the expression of beta2-
      and beta3-adrenoceptors in endothelial and/or smooth muscle cells in blood
      vessels of SH compared to WKY rats. The evidence suggests that beta2-adrenoceptor
      stimulation and SNP infusion reduce PWV independently from reduction in blood
      pressure in a state of high systemic arterial pressure. A reduction in vascular
      tone of the central arteries may play a key role in decreasing PWV that is
      elevated due to stiffer arterial wall.

PMID- 29208474
TI  - Caenorhabditis elegans as a model system for target identification and drug
      screening against neurodegenerative diseases.
AB  - Over the past decades, Caenorhabditis elegans (C. elegans) has been widely used
      as a model system because of its small size, transparent body, short generation
      time and lifespan (~3 days and 3 weeks, respectively), completely sequenced
      genome and tractability to genetic manipulation. Protein misfolding and
      aggregation are key pathological features in neurodegenerative diseases such as
      Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic
      lateral sclerosis. Animal models, including C. elegans, have been extensively
      used to discover and validate new drugs against neurodegenerative diseases. The
      well-defined and genetically tractable nervous system of C. elegans offers an
      effective model to explore basic mechanistic pathways of neurodegenerative
      diseases. Recent progress in high-throughput drug screening also provides a
      powerful approach for identifying chemical modulators of biological processes.
      Here, we summarize the latest progress of using C. elegans as a model system for
      target identification and drug screening in neurodegenerative diseases.

PMID- 29208475
TI  - Cortical bone trajectory screws fixation in lumbar adjacent segment disease: A
      technique note with case series.
AB  - Lumbar adjacent segment disease after lumbar fusion surgery often requires
      surgical intervention. However, subsequent surgical treatment often needs to
      expose and remove all of the previous instruments. This additional surgery leads
      to significant post-operative pain, muscular fibrosis, poor wound healing and
      infection, etc. From October 2015 to March 2016, we collected six cases underwent
      cortical bone trajectory screws fixation with minimal invasive inter-body cage
      fusion for lumbar adjacent segment disease. Patients in the study all had
      improvement after surgery without recurrence or instruments failure during follow
      up. The technique negates removal of pre-existing instruments and when combined
      with minimal invasive fusion surgery, the wound length, blood loss and soft
      tissue damage could be reduced compared with traditional surgery. We introduce
      the surgical procedures in detail and wish this technique could be an option for
      spine surgeons who encounter a similar situation.

PMID- 29208476
TI  - What does best evidence tell us about robotic gait rehabilitation in stroke
      patients: A systematic review and meta-analysis.
AB  - BACKGROUND: Studies about electromechanical-assisted devices proved the validity
      and effectiveness of these tools in gait rehabilitation, especially if used in
      association with conventional physiotherapy in stroke patients. OBJECTIVE: The
      aim of this study was to compare the effects of different robotic devices in
      improving post-stroke gait abnormalities. METHODS: A computerized literature
      research of articles was conducted in the databases MEDLINE, PEDro, COCHRANE,
      besides a search for the same items in the Library System of the University of
      Parma (Italy). We selected 13 randomized controlled trials, and the results were
      divided into sub-acute stroke patients and chronic stroke patients. We selected
      studies including at least one of the following test: 10-Meter Walking Test, 6
      Minute Walk Test, Timed-Up-and-Go, 5-Meter Walk Test, and Functional Ambulation
      Categories. RESULTS: Stroke patients who received physiotherapy treatment in
      combination with robotic devices, such as Lokomat or Gait Trainer, were more
      likely to reach better results, compared to patients who receive conventional
      gait training alone. Moreover, electromechanical-assisted gait training in
      association with Functional Electrical Stimulations produced more benefits than
      the only robotic treatment (-0.80 [-1.14; -0.46], p > .05). CONCLUSIONS: The
      evaluation of the results confirm that the use of robotics can positively affect
      the outcome of a gait rehabilitation in patients with stroke. The effects of
      different devices seems to be similar on the most commonly outcome evaluated by
      this review.

PMID- 29208477
TI  - Impact of Opioid Therapy on Sleep and Respiratory Patterns in Adults With
      Advanced Cancer Receiving Palliative Care.
AB  - CONTEXT: In advanced cancer, abnormal sleep patterns may contribute to poor
      quality of life, but the impact of opioid-related sleep disorders has not been
      explored in detail in these patients. OBJECTIVE: To document sleep and
      respiratory patterns in patients with cancer, receiving a range of opioids,
      determine factors that contribute to severity of central or obstructive apnea,
      and to what extent these contribute to sleep disturbance. METHODS: Adults with
      advanced cancer admitted to a palliative care service underwent a sleep analysis
      by an unattended polysomnography. Total sleep time, apnea hypopnea index, central
      apnea index, obstructive apnea hypopnea index, arousal index, and oxygen
      desaturation were measured. Baseline assessment included body habitus, Mallampati
      score, comorbidity indices, concomitant medications, and the Berlin
      questionnaire. Epworth Sleepiness Scale, Stanford Sleepiness Scale, and Wu cancer
      fatigue scales were documented. RESULTS: Twenty-eight patients were studied,
      including 25 receiving opioids. In the latter group, the apnea hypopnea index was
      mildly abnormal in six patients and severely abnormal in 10 patients. Central
      apnea index and obstructive apnea hypopnea index were abnormal in nine and 17
      patients, respectively. There was no significant correlation between opioid dose
      and polysomnographic results. CONCLUSION: In patients with advanced cancer
      receiving opioid analgesia, there was a high prevalence of respiratory
      disturbance, both central and obstructive, and deranged sleep patterns.
      Addressing sleep-disordered breathing in cancer patients has the potential to
      improve daytime drowsiness and quality of life.

PMID- 29208478
TI  - Pilot Testing of a Brief Couple-Based Mind-Body Intervention for Patients With
      Metastatic Non-Small Cell Lung Cancer and Their Partners.
AB  - CONTEXT: Given the generally incurable nature of metastatic lung cancer, patients
      and their spouses/partners are at risk for psychological and spiritual distress.
      To address this concern, we developed a couple-based mind-body (CBMB)
      intervention. OBJECTIVES: This formative research aimed at examining the
      intervention's acceptability and initial efficacy in patients with metastatic
      lung cancer undergoing treatment and their spouses. METHODS: Intervention content
      evaluation sessions and an ensuing single-arm trial were conducted. To evaluate
      intervention content, participants performed intervention exercises and then
      participated in semistructured interviews and completed written evaluations. In
      the single-arm trial, four intervention sessions were delivered over two weeks,
      focusing on cultivating mindfulness, interpersonal connection, gratitude, and
      purpose. Newly recruited couples completed measures of depressive symptoms,
      cancer distress, spiritual well-being, and sleep disturbances before and after
      the intervention. RESULTS: Content evaluations by seven dyads of patients and
      their partners revealed high acceptability ratings for the CBMB intervention
      (e.g., all participants would recommend the intervention). Consent and adherence
      rates (54% and 67%, respectively) were acceptable in the single-arm trial. All
      patients (n = 7 dyads; 67% male; mean age, 55 years) and partners (33% male; mean
      age, 59 years) rated the intervention as useful. Paired t-test analyses revealed
      large effect sizes for reduced sleep disturbances (d = 1.83) and medium effect
      sizes for cancer-specific distress (d = 0.61) for patients and large effect sizes
      for depressive symptoms (d = 0.90) for partners. CONCLUSION: Based on these
      results, the CBMB intervention appears to be acceptable and subjectively useful.
      In addition, we observed preliminary evidence of quality of life gains in both
      patients and their partners.

PMID- 29208479
TI  - Ninety Day Mortality and Overall Survival after Radical Radiotherapy for Non
      small Cell Lung Cancer.

PMID- 29208480
TI  - Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated
      Patients Affected by Recurrent Prostate Cancer.
AB  - AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged
      as a valuable option for exclusive local failure after prior external beam
      radiation therapy (EBRT) for localised prostate cancer. The aim of this study was
      to assess the efficacy and safety of rSBRT in patients experiencing locally
      recurrent prostate cancer after prior definitive or postoperative radiotherapy
      using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were
      retrospectively reviewed. Local recurrence was assessed by 18F-choline positron
      emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was
      delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2
      months, 6 months and every 4 months thereafter. Toxicity was assessed according
      to CTCAE v.4.03. RESULTS: All patients received prior EBRT. The median EQD2 total
      dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation
      after prior biochemical failure. At 6 months, 41 patients showed a median PSA
      decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA
      elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was
      80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P =
      0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard
      ratio 2.98). Neither clinical variables nor dosimetric parameters were found to
      be predictive for toxicity. CONCLUSION: Focal rSBRT can achieve durable remission
      in locally relapsing patients and systemic treatment can be postponed with
      acceptable toxicity. Accurate patient selection is mandatory to maximise disease
      control.

PMID- 29208481
TI  - Detection thresholds for four different fatty stimuli are associated with
      increased dietary intake of processed high-caloric food.
AB  - BMI-specific differences in food choice and energy intake have been suggested to
      modulate taste perception. However, associations between body composition and fat
      taste sensitivity are controversial. The objective of this study was to examine
      the association between body composition, dietary intake and detection thresholds
      of four fatty stimuli (oleic acid, paraffin oil, canola oil, and canola oil
      spiked with oleic acid) that could be perceived via gustatory and/or textural
      cues. In 30 participants, fat detection thresholds were determined in a repeated
      measurements design over twelve days. Weight status was examined by measuring the
      participants' BMI, waist circumference and waist-to-hip ratio. The habitual food
      intake was assessed via several questionnaires and twelve, non-consecutive 24
      hour food diaries. In this study, a negative correlation was found between fat
      detection thresholds and the intake of food rich in vitamins and fibre. Moreover,
      a positive correlation was identified between the intake of high-fat food and fat
      detection thresholds. No differences in fat detection thresholds were observed
      due to variations in BMI or waist-to-hip ratio. These findings indicate that a
      regular intake of fatty foods might decrease an individuals' perceptual response
      to fats which might lead to excess fat intake on the long term.

PMID- 29208482
TI  - What motivates women to breastfeed in Lebanon: An exploratory qualitative
      analysis.
AB  - This exploratory qualitative study examined the influence of injunctive and
      descriptive norms on breastfeeding, a health-improving behaviour related to a
      highly committed personal decision. The research explores the different
      mechanisms through which social norms impact breastfeeding behaviour pre or post
      adoption of breastfeeding practice. A qualitative approach was used by performing
      in-depth analysis of cross-sectional accounts of women in Lebanon contemplating
      adoption of breastfeeding practice and women who already breastfed. Interviews
      were also conducted with medical professionals, lactation specialists, and
      breastfeeding activists. On one hand, the attitude of the medical professionals
      and the government efforts are two mechanisms that stimulate the injunctive
      norms. On the other hand, the descriptive norms are defined by community attitude
      aggregated with societal beliefs and expectations on women's image and role in
      society. Both types of social norms are in constant interplay with personal norms
      and each type becomes more salient at different periods over time. The findings
      suggest that social norms are major determinants of breastfeeding behaviour. The
      influence of the type of social norm-descriptive or injunctive-on the decision to
      breastfeed varies according to the moment of life the mother is living.
      Theoretical and practical implications are discussed.

PMID- 29208483
TI  - Initial validation of the Nine Item Avoidant/Restrictive Food Intake disorder
      screen (NIAS): A measure of three restrictive eating patterns.
AB  - Avoidant/Restrictive Food Intake Disorder (ARFID) is an eating or feeding
      disorder characterized by inadequate nutritional or caloric intake leading to
      weight loss, nutritional deficiency, supplement dependence, and/or significant
      psychosocial impairment. DSM-5 lists three different eating patterns that can
      lead to symptoms of ARFID: avoidance of foods due to their sensory properties
      (e.g., picky eating), poor appetite or limited interest in eating, or fear of
      negative consequences from eating. Research on the prevalence and psychopathology
      of ARFID is limited by the lack of validated instruments to measure these eating
      behaviors. The present study describes the development and validation of the nine
      item ARFID screen (NIAS), a brief multidimensional instrument to measure ARFID
      associated eating behaviors. Participants were 455 adults recruited on Amazon's
      Mechanical Turk, 505 adults recruited from a nationally-representative subject
      pool, and 311 undergraduates participating in research for course credit.
      Exploratory and confirmatory factor analyses provided evidence for three factors.
      The NIAS subscales demonstrated high internal consistency, test-retest
      reliability, invariant item loadings between two samples, and
      convergent/discriminant validity with other measures of picky eating, appetite,
      fear of negative consequences, and psychopathology. The scales were also
      correlated with measures of ARFID-like symptoms (e.g., low BMI, low
      fruit/vegetable variety and intake, and eating-related psychosocial
      interference/distress), although the picky eating, appetite, and fear scales had
      distinct independent relationships with these constructs. The NIAS is a brief,
      reliable instrument that may be used to further investigate ARFID-related eating
      behaviors.

PMID- 29208484
TI  - Value of 18F-FDG PET/CT in the diagnosis of chorea-acanthocytosis.

PMID- 29208485
TI  - Lactational exposure of polychlorinated biphenyls impair Leydig cellular
      steroidogenesis in F1 progeny rats.
AB  - The present study was aimed to determine the effects of lactational exposure of
      PCBs (Aroclor 1254) on Leydig cellular steroidogenesis in F1 progeny rats.
      Lactating dams were orally treated by gavage with different doses of PCBs (1, 2
      and 5mg/kg b.wt./day). Male progenies were sacrificed on PND60. Our results
      demonstrated that exposure to PCBs decreased the body weight, testis weight and
      anogenital distance (AGD) index in the F1 progeny rats. Importantly, PCBs
      exposure reduced the serum levels of LH, testosterone and estradiol.
      Interestingly, PCBs caused a decrease in the Leydig cell population along with
      decreased activities of steroidogenic enzymes 3beta- and 17beta-HSD.
      Additionally, we observed a significant decrease in LHR, SR-B1, StAR protein,
      Cyp11a1, 3beta-HSD, Cyp17a1, 17beta-HSD, 5alpha-reductase, Cyp19a1 and AR gene
      expression in the Leydig cells of progeny rats. In conclusion, our study
      demonstrates that lactational exposure of PCBs alters Leydig cellular
      steroidogenesis in the F1 progeny rats.

PMID- 29208487
TI  - In-vitro comparison of mechanical resistance between two straight plates and a Y
      plate for fixation of mandibular condyle fractures.
AB  - OBJECTIVE: To compare the mechanical resistance of conventional plates with a
      modified Y-plate in mandibular condyle fracture. MATERIALS AND METHODS: 40
      synthetic hemi-mandibular polyurethane replicates were used. Two groups of fixing
      materials were included: 20 mandibles fixed with 40 straight plates with four
      roles each (2.0 mm system) and 20 mandibles fixed with 20 Y-shaped plates (2.0 mm
      system and 1.5 mm thickness). The samples were submitted to linear loading in the
      following directions: 10 mandibles from each group from lateral to medial and 10
      mandibles from each group from anterior to posterior. A universal loading
      machine, Instron Universal 4411, was used to performed the tests, and the
      resistance of each fixed mandible was assessed at displacements of 1 mm, 3 mm,
      and 5 mm. The t-test for independent samples was performed. The p value was set
      at <0.05. RESULTS: The worst mechanical resistance was found in the Y-plates
      loaded from anterior to posterior. The best mechanical resistance was in two
      straight hole plates loaded from lateral to medial. The Y-plates and two straight
      hole plates showed similar resistance when a lateral to medial load was applied.
      CONCLUSION: There was no difference between the plates when lateral to medial
      loading was tested.

PMID- 29208486
TI  - Controlled-release biodegradable nanoparticles: From preparation to vaginal
      applications.
AB  - This study aimed to prepare poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles
      (NPs) with chitosan (CTS) surface modification to be used as a vaginal delivery
      system for antimycotic drugs. Clotrimazole was encapsulated with entrapment
      efficiencies of 86.1 and 68.9% into Clotrimazole-PLGA-NPs (CLT-PLGA-NPs) and PLGA
      NPs with CTS-modified surface (CLT-PLGA-CTS-NPs), respectively. The later NPs
      exhibited a larger size and higher positive zeta potential (Z potential) in
      comparison to unmodified NPs. In vitro release kinetic studies indicated that
      Clotrimazole was released in percentages of >98% from both nanoparticulate
      systems after 18days. Antifungal activity and mucoadhesive properties of NPs were
      enhanced when CTS was added onto the surface. In summary, these results suggested
      that Clotrimazole loaded into PLGA-CTS-NPs has great potential for vaginal
      applications in treating vaginal infections generated by Candida albicans.

PMID- 29208488
TI  - Multi-targeted effects of G4-aptamers and their antiproliferative activity
      against cancer cells.
AB  - We selected and investigated nine G-quadruplex (G4)-forming aptamers originally
      designed against different proteins involved in the regulation of cellular
      proliferation (STAT3, nucleolin, TOP1, SP1, VEGF, and SHP-2) and considered to be
      potential anticancer agents. We showed that under physiological conditions all
      the aptamers form stable G4s of different topology. G4 aptamers designed against
      STAT3, nucleolin and SP1 inhibit STAT3 transcriptional activity in human breast
      adenocarcinoma MCF-7 cells, and all the studied aptamers inhibit TOP1-mediated
      relaxation of supercoiled plasmid DNA. STAT3 inhibition by G4 aptamer designed
      against SP1 protein provides a new explanation for the SP1 and STAT3 crosstalk
      described recently. We found some correlation between G4-mediated inhibition of
      the DNA replication and TOP1 activity. Four G4 aptamers from our dataset that
      appeared to be the strongest TOP1 inhibitors most efficiently decreased de novo
      DNA synthesis, by up to 79-87%. Seven G4 aptamers demonstrated significantly
      higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells than
      on immortalized mammary epithelial MCF-10A cells. Pleiotropic properties of G4
      aptamers and their high specificity against cancer cells observed for the
      majority of the studied G4 aptamers allowed us to present them as promising
      candidates for multi-targeted cancer therapy.

PMID- 29208489
TI  - Relaxing access to liver transplantation with living donation: A foolish move or
      a time to change?

PMID- 29208490
TI  - Fluorescence enlightens RND pump activity and the intrabacterial concentration of
      antibiotics.
AB  - To understand antibiotic resistance in Gram-negative bacteria, a key point is to
      investigate antibiotic accumulation, which is defined by influx and efflux.
      Several methods exist to evaluate membrane permeability and efflux pump activity,
      but they present disadvantages and limitations. An optimized spectrofluorimetric
      method using intrinsic tryptophan fluorescence as an internal standard, as well
      as a complementary microfluorimetric assay following time-course accumulation in
      intact individual cells, have been developed. Comparing the latter population and
      single cell approaches can lead to an understanding of phenotypic heterogeneity
      within a population. The two methodologies lead to determination of parameters,
      concentration, accumulation rates and localization that contribute to emerging
      concepts (RTC2T, SICAR) with the aim of identifying and detailing antibiotic
      chemotypes involved in influx/efflux.

PMID- 29208491
TI  - Feedback information and the reward positivity.
AB  - The reward positivity is a component of the event-related brain potential (ERP)
      sensitive to neural mechanisms of reward processing. Multiple studies have
      demonstrated that reward positivity amplitude indices a reward prediction error
      signal that is fundamental to theories of reinforcement learning. However,
      whether this ERP component is also sensitive to richer forms of performance
      information important for supervised learning is less clear. To investigate this
      question, we recorded the electroencephalogram from participants engaged in a
      time estimation task in which the type of error information conveyed by feedback
      stimuli was systematically varied across conditions. Consistent with our
      predictions, we found that reward positivity amplitude decreased in relation to
      increasing information content of the feedback, and that reward positivity
      amplitude was unrelated to trial-to-trial behavioral adjustments in task
      performance. By contrast, a series of exploratory analyses revealed frontal
      central and posterior ERP components immediately following the reward positivity
      that related to these processes. Taken in the context of the wider literature,
      these results suggest that the reward positivity is produced by a neural
      mechanism that motivates task performance, whereas the later ERP components apply
      the feedback information according to principles of supervised learning.

PMID- 29208492
TI  - Resting state connectivity mediates the relationship between collectivism and
      social cognition.
AB  - Humans are intrinsically social beings and it is natural that self-processing is
      associated with social cognition. The degree to which the self is perceived as a
      part of social environment is modulated by cultural stereotypes, such as
      collectivism and individualism. Here, we tested the hypothesis that individuals
      who endorse collectivist values would spontaneously think more about their
      relationships with other people and this association would be mediated by
      connectivity between the medial prefrontal cortex (MPFC) and the rest of the
      brain. Connectivity was evaluated based on resting state EEG data using the
      recently developed methods, which combine beamformer spatial filtering with seed
      based connectivity estimation. The formal mediation analysis revealed that
      collectivism is associated with an enhanced connectivity of MPFC with a set of
      cortical regions that are frequently co-activated in moral reasoning, empathy,
      and theory of mind tasks and with diminished connectivity with the
      precuneus?posterior cingulate cortex, which is involved in self-centered
      cognition. The relationship between collectivism and social cognition was
      mediated by MPFC connectivity with the left middle temporal gyrus implying that
      in participants with collectivistic attitude, thinking about relationships with
      other people may be associated with semantic memory retrieval and reasoning on
      moral issues and others' intentions.

PMID- 29208493
TI  - Almond, hazelnut and walnut, three nuts for neuroprotection in Alzheimer's
      disease: A neuropharmacological review of their bioactive constituents.
AB  - An increase in the prevalence of Alzheimer's disease (AD) as a multifactorial
      neurodegenerative disorder is an almost obvious issue in the world. Researches on
      natural products for finding effective drugs to prevent the disease are in
      progress. There is special attention to the three types of nuts including almond,
      hazelnut and walnut in manuscripts of traditional Persian medicine (PM) as the
      preventive agents against brainatrophy and memory loss. The purpose of this study
      is a pharmacological review of their bioactive constituents and introducing the
      value of these nuts as the effective supplements and natural medicinal foods in
      AD patients. Databases including PubMed and ScienceDirect were searched in title,
      abstract and keywords from year 2000 to present for AD-related researches on
      these tree nuts, their major phytochemicals and their mechanisms of action. As
      result, almond, hazelnut and walnut provide macronutrients, micronutrients, and
      phytochemicals which affect several pathways in AD pathogenesis such as
      amyloidogenesis, tau phosphorylation, oxidative stress, cholinergic pathways, and
      some non-target mechanisms including cholesterol lowering and anti-inflammatory
      properties, as well as effect on neurogenesis. These nuts are recommended in PM
      for their brain-protective activity and particularly reversing brain atrophy in
      case of hazelnut. The therapeutical statements of PM scholars mentioned in their
      books are based on their clinical observations with support of a long history of
      experiences. Beyond the molecular activities attributed to the phytochemicals,
      the use of these tree nuts could be more considered in scientific researches as
      the effective nutrients for prevention or even management of AD.

PMID- 29208494
TI  - Bleeding in advanced CKD patients on antithrombotic medication - A critical
      appraisal.
AB  - Patients with advanced chronic kidney disease (CKD) are at an increased risk of
      bleeding, especially in the context of the complex therapeutic schemes of
      coronary artery disease (CAD) (from stable angina to acute coronary syndromes),
      atrial fibrillation or venous thromboembolism. The bleeding issue increases
      morbidity and mortality, a serious problem in daily medical practice. However,
      these patients are largely excluded from major randomized clinical trials, which
      results in the lack of medical evidence-based foundation for specific
      recommendations regarding antithrombotic treatment in a high bleeding risk
      setting. Within this framework, the clinician does not benefit from a clear set
      of algorithms and measures in the exploration and balancing of bleeding and
      thrombosis risks. We discuss a diversity of scenarios, encompassing all
      categories of advanced CKD patients with CAD or/and atrial fibrillation, and with
      various combinations of drugs, such as antiplatelet therapy or/and oral
      anticoagulation. Our review highlights the most recent research as well as
      existing gaps in the recommendations of European Society of Cardiology
      Guidelines. We evaluate the existence or lack of assessment tools for the
      bleeding risk, strength, reliability and usefulness of the bleeding risk scores.
      Also, we identify all the measures recommended after risk evaluation, including
      specific plans, dose adjustments and particular therapeutic approaches. Finally,
      we provide with suggestions for improving the management of this patient
      population.

PMID- 29208495
TI  - Peptidoglycan recognition protein of Solen grandis (SgPGRP-S1) mediates immune
      recognition and bacteria clearance.
AB  - Peptidoglycan recognition proteins (PGRPs) are indispensable molecules in innate
      immunity due to their prominent function in sensing and eliminating invading
      microorganisms. In the present study, a short type PGRP from razor clam Solen
      grandis (SgPGRP-S1) was recombinantly expressed and purified to investigate its
      potential function in innate immunity. As a pattern recognition receptor,
      recombinant SgPGRP-S1 (rSgPGRP-S1) specifically bind Lys-type and Dap-type
      peptidoglycan in vitro, but not lipopolysaccharide or beta-glucan. The
      peptidoglycan binding ability of rSgPGRP-S1 resulted in significant agglutination
      activity against Gram-negative Escherichia coli and Listonella anguillarum, as
      well as Gram-positive Micrococcus luteus. Furthermore, rSgPGRP-S1 was
      bactericidal, significantly suppressing the growth of both E. coli and Gram
      positive Staphylococcus aureus. The protein also exhibited strong amidase
      activity and degraded bacterial peptidoglycan in the presence of Zn2+, suggesting
      amidase activity might contribute to SgPGRP-S1 antibacterial activity. These
      results indicate SgPGRP-S1 is multifunctional in innate immunity, mediating both
      immune recognition and bacteria elimination.

PMID- 29208496
TI  - Effect of stocking density on growth performance, digestive enzyme activities,
      and nonspecific immune parameters of Palaemonetes sinensis.
AB  - Palaemonetes sinensis is a new breed of shrimp with great potential for
      aquaculture, which has been confirmed in our previous production tests. However,
      there are limited reports about this species and its biological information is
      scarce. This study describes the effect of stocking density on the growth,
      digestive enzyme activities, and nonspecific immunity of P. sinensis with an
      initial average body weight was 0.25 +/- 0.02 g. Groups of shrimps were reared at
      four different initial densities (2.5, 5, 10, and 20 individuals.L-1). After 30
      days of culture, the results indicated that the final body weight, weight gain,
      and specific growth rate were higher in shrimps grown in groups of 10
      individuals.L-1 than other groups, but the survival rates of these shrimp were
      significantly lower than those reared in group of 2.5 or 5 individuals.L-1. The
      trypsin, amylase, and lipase activities of shrimp significantly decreased with
      increase in stocking density. Nonspecific immune indicators decreased
      significantly with increase in density, but there were no significant differences
      between the 2.5 and 5 individuals.L-1 groups in terms of the total haemocyte
      count (THC), phenoloxidase activity (PO), lysozyme (LZM), catalase (CAT), and
      superoxide dismutase (SOD). These results suggest that increasing the stocking
      density from 2.5 to 5 individuals.L-1 did not affect any of the detected
      indicators of P. sinensis, but there are shelter in farming mode is better for
      culture of P. sinensis up to 10 individuals L-1.

PMID- 29208497
TI  - Molecular cloning, expression, promoter analysis and functional characterization
      of a new Crustin from Litopenaeus vannamei.
AB  - Antimicrobial peptides (AMPs) are the most important players in the innate immune
      system, providing a principal first-line of defense against the invading
      pathogens. Crustin, a type of whey acidic protein (WAP) domain-containing and
      cationic cysteine-rich AMP, can function in a protease inhibition or an effector
      molecule manner. In the present study, a new Crustin was cloned and identified
      from Pacific white shrimp Litopenaeus vannamei and designated as LvCrustinA. The
      full-length cDNA of LvCrustinA was 687 bp, with a 519 bp open reading frame (ORF)
      that encoded a peptide of 172 amino acids. Domain analysis indicated that
      LvCrustinA contained a Glycine-rich region in the N-terminal and a single WAP
      domain within eight cysteines in the C-terminal. The 5' upstream regulatory
      sequence of 1249 bp (promoter) was obtained using a genome walking method, and it
      contained several conserved transcription factors binding motifs including NF
      kappaB, AP-1 and STAT (Signal transducers and activators of transcription). Dual
      reporter assay showed that NF-kappaB transcription factors LvDorsal and LvRelish,
      and AP-1 transcription factor Lvc-Jun could up-regulate the promoter activity of
      LvCrustinA, suggesting that NF-kappaB and JNK-c-Jun pathways could be involved in
      regulating the expression of LvCrustinA. Moreover, LvCrustinA was abundantly
      expressed in immune related tissues such as gill, hemocyte and epithelium, and
      its expression was up-regulated in response to Vibrio parahaemolyticus and White
      spot syndrome virus (WSSV) challenges in gill tissue, suggesting that LvCrustinA
      could be involved in the host defense against bacterial and viral infection.
      Additionally, RNAi mediated knockdown of LvCrustinA resulted in shrimps with the
      higher cumulative mortality during V. parahaemolyticus and WSSV infection. Taken
      together, these results provided some insight into the expression and
      transcriptional regulatory role of LvCrustinA, and its defensive role against
      pathogenic infection.

PMID- 29208498
TI  - Identification and functional characterization of interferon regulatory factor 7
      involved in activation JAK/STAT pathway in miiuy croaker.
AB  - Interferon regulatory factor (IRF) family is a transcription factor family which
      plays an important role in the regulation of natural immunity and immune cell
      differentiation. IRF7 is important to regulate the response of type I interferon
      (IFN) to viral infection. Thus, more researches of the characteristic and
      functions of IRF7 should be done to get better understanding of the mechanisms
      underlying immune reactions. Here, the characterization of full-length cDNA of
      IRF7 was reported from miiuy croaker. Gene characterization analysis of mmiIRF7
      showed conservative with other fish and inferred that the difference of
      tryptophan residues in IRF7 may occurred in the period of fish-specific genome
      duplication (FSGD) or earlier. Syntenic analysis of IRF7 showed that fish IRF7
      had more highly conserved synteny than the higher vertebrates IRF7. Luciferase
      reporter assays result showed the ability of mmiIRF7 for activation of IFNalpha,
      IFNbeta, IFNgamma and ISRE luciferase reporter. In this study, we systematically
      and comprehensively analyzed evolution and function of mmiIRF7, which will
      provide the basis for future research on fish IRF family.

PMID- 29208500
TI  - Effect of microencapsulated probiotic Bacillus vireti 01-polysaccharide extract
      of Gracilaria folifera with alginate-chitosan on immunity, antioxidant activity
      and disease resistance of Macrobrachium rosenbergii against Aeromonas hydrophila
      infection.
AB  - Polysaccharide from red seaweed Gracilaria folifera has an interesting functional
      property of antioxidant activity and prebiotic effect. A feeding trial experiment
      was directed to examine the effect of probiotic bacteria Bacillus vireti 01
      microencapsulated with G. folifera polysaccharide against freshwater prawn M.
      rosenbergii. Three different feeding trials were conducted for 15 days. The first
      group contained prawns fed with commercial diet. The second group was comprised
      of Aeromonas hydrophila challenged prawns fed with commercial feed. The third
      group consisted of A. hydrophila challenged prawns fed with microencapsulated
      probiotic-polysaccharide. Survival percentage was significantly decreased in
      prawns of group2 as compared to that of group1 and group3 prawns (p < 0.0001).
      The immunological parameters and antioxidant activities (p < 0.001) were found to
      be increased in group three prawns which were fed with encapsulated probiotic
      seaweed polysaccharide and challenged with A. hydrophila as compared to that of
      group1 and group2. Tissue necrosis, fused lamella, haemocyte infiltration and
      damage of hepatopancreas lumen and tubule were noted in group2 prawns. There was
      no histological changes were observed in group3 prawns in which the histological
      architecture was similar to the control group1. The results suggested that
      combination of encapsulated probiotic B. vireti 01 and seaweed polysaccharide as
      dietary feed showed an enhancement of immune response, antioxidant activity and
      disease resistant of M. rosenbergii against A. hydrophila.

PMID- 29208499
TI  - Identification of SNP markers associated with tolerance to ammonia toxicity by
      selective genotyping from de novo assembled transcriptome in Litopenaeus
      vannamei.
AB  - The high concentration of ammonia from deteriorated aquaculture environments and
      the intensive culture system could increase the susceptibility to pathogens and
      even cause high mortality in Litopenaeus vannamei. In addition, we have revealed
      that the ammonia-tolerant shrimp also have high disease resistance in L.
      vannamei. In the present study, in order to identify SNP markers associated with
      tolerance to ammonia toxicity, we developed and characterized SNPs from our
      previous transcriptome sequencing data of ammonia-stressed and control groups,
      and a marker-trait association analysis was performed for marker-assisted
      selection (MAS) to increase production in L. vannamei. A total of 318,919 SNPs
      were identified from the transcriptome sequences, and 25,772 SNPs were found from
      the 1826 ammonia-responsive genes with functional annotation. We selected 49 SNPs
      from 26 ammonia-responsive genes that had strong homologies to known genes in the
      shrimp and probably involved in immune function as candidate markers for
      genotyping, among which 39 SNPs were polymorphic for further marker-trait
      association analysis with the ammonia-tolerant (AT) and ammonia-sensitive (AS)
      groups. Finally, 12 out of the 49 SNP markers were identified to be associated
      with ammonia tolerance, containing 10 loci with significantly different allele
      frequencies and 10 loci with significantly different genotyping frequencies
      between the AT and AS groups. Among the associated markers, the G allele of TSP-1
      (the first locus from the thrombospondin gene), the A allele of TSP-3, and the C
      allele of XBP1-5 (the fifth locus from X-box binding protein 1) only presented in
      the AT groups, but they were absent from the AS groups, which would be the
      preference of the MAS for the ammonia-tolerant shrimp. In addition, when the 12
      associated SNP markers were used for analysis, the genetic diversity of the AT
      groups were significantly higher than that of the AS groups, but when the 39 loci
      were used there was no difference. This is the first report for the markers
      associated with ammonia tolerance in this species, indirectly with disease
      resistance, which provided important potential for genetic selection to increase
      survival rate and production in shrimp farming.

PMID- 29208501
TI  - Autophagic processes in Mytilus galloprovincialis hemocytes: Effects of Vibrio
      tapetis.
AB  - Autophagy is a highly conserved and regulated catabolic process involved in
      maintaining cell homeostasis in response to different stressors. The autophagic
      machinery is also used as an innate immune mechanism against microbial infection.
      In invertebrates, that lack acquired immunity, autophagy may thus play a key role
      in the protection against potential pathogens. In aquatic molluscs, evidence has
      been provided for induction of autophagy by starvation and different
      environmental stressors; however, no information is available on autophagic
      pathways in the immune cells, the hemocytes. In this work, the autophagic
      processes were investigated in the hemocytes of the marine bivalve, the mussel
      Mytilus galloprovincialis. The effects of classical inducers/inhibitors of
      mammalian autophagy were first tested. Rapamycin induced a decrease in lysosomal
      membrane stability-LMS that was prevented by the autophagy inhibitor Wortmannin.
      Increased MDC fluorescence and expression of LC3-II were also observed. Moreover,
      responses to in vitro challenge with the bivalve pathogen Vibrio tapetis were
      evaluated. Mussel hemocytes were unable to activate the immune response towards
      V. tapetis; however, bacterial challenge induced a moderate decrease in LMS,
      corresponding to lysosomal activation but no cytotoxicity; the effect was
      prevented by Wortmannin. TEM observations showed that V. tapetis resulted in
      rapid formation of autophagosomes and autolysosomes. Accordingly, increased LC3
      II expression, decreased levels of phosphorylated mTor and of p62 were observed.
      The results represent the first evidence for autophagic processes in bivalve
      hemocytes in response to bacterial challenge, and underline the protective role
      of autophagy towards potential pathogenic vibrios.

PMID- 29208502
TI  - Rate of caesarean sections according to the Robson classification: Analysis in a
      French perinatal network - Interest and limitations of the French medico
      administrative data (PMSI).
AB  - INTRODUCTION: The objective of our study was to determine, in accordance with WHO
      recommendations, the rates of Caesarean sections in a French perinatal network
      according to the Robson classification and determine the benefit of the medico
      administrative data (PMSI) to collect this indicator. This study aimed to
      identify the main groups contributing to local variations in the rates of
      Caesarean sections. MATERIAL AND METHODS: A descriptive multicentric study was
      conducted in 13 maternity units of a French perinatal network. The rates of
      Caesarean sections and the contribution of each group of the Robson
      classification were calculated for all Caesarean sections performed in 2014. The
      agreement of the classification of Caesarean sections according to Robson using
      medico-administrative data and data collected in the patient records was measured
      by the Kappa index. We also analysed a 6 groups simplified Robson classification
      only using data from PMSI, which do not inform about parity and onset of labour.
      RESULTS: The rate of Caesarean sections was 19% (14.5-33.2) in 2014 (2924 out of
      15413 deliveries). The most important contributors to the total rates were groups
      1, 2 and 5, representing respectively 14.3%, 16.7% and 32.1% of the Caesarean
      sections. The rates were significantly different in level 1, 2b and 3 maternity
      units in groups 1 to 4, level 2a maternity units in group 5, and level 3
      maternity units in groups 6 and 7. The agreement between the simplified Robson
      classification produced using the medical records and the medico-administrative
      data was excellent, with a Kappa index of 0.985 (0.980-0.990). CONCLUSION: To
      reduce the rates of Caesarean sections, audits should be conducted on groups 1, 2
      and 5 and local protocols developed. Simply by collecting the parity data, the
      excellent metrological quality of the medico-administrative data would allow
      systematisation of the Robson classification for each hospital.

PMID- 29208503
TI  - Maternal complications induced by digoxin treatment of fetal tachycardia: A
      retrospective series of 18 cases.
AB  - OBJECTIVE: To evaluate maternal tolerance to digoxin, used alone or associated to
      other antiarrhythmic drugs in the management of fetal tachycardia. PATIENTS AND
      METHODS: This retrospective study was conducted at Rouen University Hospital
      between January 2009 and July 2016. All women who have received a treatment by
      either digoxin alone or associated with another antiarrhythmic drug for fetal
      tachycardia were included in the study. Maternal cardiac and extracardiac adverse
      effects were reported and comparisons between electrocardiograms before and
      during treatment with digoxin alone were performed. RESULTS: Eighteen women were
      treated by digoxin, either alone or associated with another antiarrhythmic
      (sotalol, flecainide or amiodarone). During treatment, digoxin overdosing
      (>2ng/mL) was observed in 11 women (61%), among which 4 women had toxic levels of
      digoxinemia (>3ng/mL) that was symptomatic in 3 women. Cardiac complications such
      as sinus bradycardia, first-degree auriculo-ventricular block and Mobitz I second
      degree auriculo-ventricular block were reported in four women (18.2%).
      Extracardiac side effects i.e. neurosensorial or digestive were diagnosed in
      35.3% of women. The parameters of the electrocardiogram were not altered before
      and after treatment with digoxin alone. CONCLUSION: Antiarrhythmics can cause
      maternal cardiac complications and extracardiac side effects that can sometimes
      be severe but rapidly reversible upon treatment arrest.

PMID- 29208504
TI  - Hepatoprotective effects of garlic against ethanol-induced liver injury: A mini
      review.
AB  - Alcoholic liver disease (ALD) is a progressively aggravated liver disease with a
      diverse spectrum from steatosis to hepatitis, fibrosis, and cirrhosis.
      Epidemiological studies reveal that alcohol is one of the major causes of
      advanced liver disease in Europe, United States, and China. Despite the
      considerable harm, progression in ALD research is slow and the current therapies
      for ALD have less efficient. Garlic (Allium sativum) has been used as a flavoring
      agent and also a folk medicine since ancient time. Along with the prosperity in
      the use of herbal medicines for the treatment of human diseases in recent
      decades, a series of studies have focused on the beneficial effects of garlic
      against ALD. This mini-review highlighted the protective roles of garlic against
      ALD and the potential mechanisms.

PMID- 29208505
TI  - Toxicological analysis of roast duck flavor components.
AB  - The aim of the study was to investigate toxicity of the synthesized roast duck
      flavor through animal experiment (mice feeding with the flavor for 35 days), and
      the major toxic compounds (acrylamide and 3,4-benzopyrene) were detected by high
      performance liquid chromatography. Compared with the control group, the blood
      biochemical indexes including protein content, bilirubin content, activity of
      alkaline phosphatase, activity of aspartate transaminase (AST) and alanine
      transaminase (ALT), cholesterol content, high density lipoprotein (HDL) and low
      density lipoprotein (LDL) content, triglycerides content, activity of creatine
      kinase (CK) and CK-MB, activity of cholinesterase (CHE) and lactate dehydrogenase
      (LDH), total bile acid (TBA) in high dose feeding group were significantly
      different. And body weight of mice fed by the flavor was decreased distinctly,
      and the heart weight was also decreased, while the liver weight was increased
      obviously. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities in liver and heart were significantly decreased, while methane
      dicarboxylic aldehyde (MDA) contents were increased evidently. Acrylamide was
      detected by high performance liquid-mass spectrum (HPLC-MS), and the content was
      5.21 mg/kg 3,4-benzoapryene was calculated by HPLC with fluorescence detector,
      and the content was 21.13 MUg/kg. Thus, the roast duck flavor was considered to
      be potential toxicity to human being.

PMID- 29208506
TI  - New iridoids from Verbascum nobile and their effect on lectin-induced T cell
      activation and proliferation.
AB  - The Verbascum species are widely used traditional herb remedies against
      respiratory, inflammatory conditions and disorders. In the present study methanol
      extract of the aerial parts of the endemic Verbascum nobile Velen, was
      investigated and two novel iridoid glycosides 1 and 2, together with nine known
      constituents: iridoids, phenylethanoids, and saponins characteristic of Verbascum
      genus were identified. Further, the biological activity of the extract and
      selected isolated compounds on concanavalin (Con A)-induced T cell proliferation
      and activation of human Jurkat T cell line and splenic murine CD3 T cells was
      evaluated. T cell growth was studied by colorimetric-based WST proliferation
      assay while DNA content, cell cycling, dynamic of cell proliferation, expression
      of activation markers, intracellular expression of cytokine IFN-gamma, and
      phosphorylation of ERK were analyzed by flow cytometry. Caspase-mediated
      apoptosis resulting in a poly (ADP-ribose) polymerase (PARP) cleavage was
      assessed by colorimetric in-cell kit. It was found that the extract, and all
      tested compounds (1, 2, 3 and 9) inhibited lectin-induced cell growth of Jurkat T
      cell line. The novel compounds decreased the frequencies of cells in S phase
      without causing a significant cell cycle arrest at G1 phase, caspases-mediated
      apoptosis and/or a profound change in the dynamic of splenic murine CD3+ T cell
      proliferation. Both compounds showed stronger inhibitory effect on Con A-induced
      ERK phosphorylation than the known bioactive compounds 3 and 9, and suppressed
      the expression of early activation marker CD69, the intracellular level of IFN
      gamma, and the generation of CD3+IFN-gamma+ effectors. Our data suggest that the
      novel iridoid glycosides might have a potential to modulate T cell-related
      pathologies.

PMID- 29208507
TI  - Myrtenol protects against myocardial ischemia-reperfusion injury through
      antioxidant and anti-apoptotic dependent mechanisms.
AB  - Myrtenol is a monoterpene with multiple pharmacological activities. However,
      although monoterpenes have been proposed to play beneficial roles in a variety of
      cardiac disorders, pharmacological actions of myrtenol in the heart are not yet
      reported. Hence, the aim of this study was to evaluate whether myrtenol promotes
      cardioprotection against myocardial ischemia-reperfusion (IR) injury, and the
      mechanisms involved in these effects. Male Wistar rats were orally treated for
      seven consecutive days with myrtenol (50 mg/kg) or N-acetyl cysteine (1.200
      mg/kg, NAC). Afterward, hearts were subjected to myocardial IR injury. Here, we
      show that the severe impairment of contractile performance induced by IR was
      significantly prevented by myrtenol or NAC. Moreover, myrtenol abolished aberrant
      electrocardiographic waveform (ST-segment elevation), as well as reduced life
      threatening arrhythmias and infarct size induced by IR injury. Importantly,
      myrtenol fully prevented the massive increase of cardiac reactive oxygen species
      generation and oxidative stress damage. Accordingly, myrtenol restored the
      impairment of endogenous antioxidant enzymes (superoxide dismutase, catalase,
      glutathione peroxidase and reductase) activities and balance of pro- and anti
      apoptotic pathways (Bax and Bcl-2), associated with decreased apoptotic cells.
      Taken together, our data show that myrtenol promotes cardioprotection against IR
      injury through attenuation of oxidative stress and inhibition of pro-apoptotic
      pathway.

PMID- 29208508
TI  - Scientific evidence on the links between periodontal diseases and diabetes:
      Consensus report and guidelines of the joint workshop on periodontal diseases and
      diabetes by the International diabetes Federation and the European Federation of
      Periodontology.
AB  - BACKGROUND: Diabetes and periodontitis are chronic non-communicable diseases
      independently associated with mortality and have a bidirectional relationship.
      AIMS: To update the evidence for their epidemiological and mechanistic
      associations and re-examine the impact of effective periodontal therapy upon
      metabolic control (glycated haemoglobin, HbA1C). EPIDEMIOLOGY: There is strong
      evidence that people with periodontitis have elevated risk for dysglycaemia and
      insulin resistance. Cohort studies among people with diabetes demonstrate
      significantly higher HbA1C levels in patients with periodontitis (versus
      periodontally healthy patients), but there are insufficient data among people
      with type 1 diabetes. Periodontitis is also associated with an increased risk of
      incident type 2 diabetes. MECHANISMS: Mechanistic links between periodontitis and
      diabetes involve elevations in interleukin (IL)-1-beta, tumour necrosis factor
      alpha, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin
      ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression.
      INTERVENTIONS: Periodontal therapy is safe and effective in people with diabetes,
      and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months,
      although studies involving longer-term follow-up are inconclusive. CONCLUSIONS:
      The European Federation of Periodontology (EFP) and the International Diabetes
      Federation (IDF) report consensus guidelines for physicians, oral healthcare
      professionals and patients to improve early diagnosis, prevention and
      comanagement of diabetes and periodontitis.

PMID- 29208509
TI  - The use of an intraarticular catheter on fast-track primary knee arthroplasty, is
      it a step forward?
AB  - OBJECTIVE: This study compares the efficacy in post-operative pain control of the
      intraarticular catheter compared to the epidural catheter after primary total
      knee arthroplasty. MATERIAL AND METHOD: Randomised clinical trial consisting of
      two groups of patients. A control group with intradural anaesthesia and an
      intraoperative epidural catheter (ropivacaine) and an intervention group using
      the same anaesthetic technique and an intraarticular catheter with an elastomeric
      pump (ropivacaine+dexketoprofen). Data such as demographic, anaesthetic and
      surgical variables, pain intensity according to Verbal Rating Scale, opioid use
      and complications, joint balance, onset of walking and hospital stay were
      recorded. RESULTS: A lower incidence and severity on Verbal Rating Scale and a
      better control of postoperative pain (p<.0014) were observed in the intervention
      group. Joint balance also presented significant results in flexion and 74% of
      these patients started walking before the first 36h and the control group had not
      yet done so. Regarding patient satisfaction, 54.1% of the patients were "very
      satisfied" with the use of the catheter (p>.001). Finally, the hospital stay
      decreased significantly, with 33.3% of intervention group patients discharged
      within the first 48h compared to none of the control group. DISCUSSION AND
      CONCLUSIONS: The use of the intraarticular catheter as postoperative analgesia is
      a useful and safe alternative. It reduces the possibility of side effects. It
      helps in early improvement of joint balance, onset of walking and control of
      pain. All of which increase patient satisfaction and result in a shorter period
      of hospitalisation.

PMID- 29208510
TI  - Differential impacts of individual and combined exposures of deoxynivalenol and
      zearalenone on the HepaRG human hepatic cell proteome.
AB  - : Numerous surveys have highlighted the natural co-occurrence of deoxynivalenol
      (DON) and zearalenone (ZEA) mycotoxins in food and feed. Nevertheless, data
      regarding cellular mechanisms involved in response to their individual and
      simultaneous exposures are lacking. In this study, in order to analyze how low
      mycotoxin doses could impact cellular physiology and homeostasis, proteomic
      profiles of proliferating human hepatic cells (HepaRG) exposed for 1h and 24h to
      low DON and ZEA cytotoxicity levels (0.2 and 20MUM respectively), alone or in
      combination, were analyzed by LC-MS/MS. Proteome analyses of mycotoxin-treated
      cells identified 4000 proteins with about 1.4% and 3.7% of these proteins
      exhibiting a significantly modified abundance compared to controls after 1h or
      24h, respectively. Analysis of the Gene Ontology biological process annotations
      showed that cell cycle, proliferation and/or development as well as on DNA
      metabolic processes were affected for most treatments. Overall, different
      proteins, and thus biological processes, were impacted depending on the
      considered mycotoxin and exposure duration. Finally, despite the important
      proteome changes observed following 24h exposure to both mycotoxins, only the
      uptake of ZEA by the cells was suggested by the mycotoxin quantification in cell
      supernatants. BIOLOGICAL SIGNIFICANCE: This study investigated the proteomic
      changes that occurred after DON and ZEA (individually and in combination) short
      exposures at low cytotoxicity levels in proliferating HepaRG cells using LC
      MS/MS. The obtained results showed that the cellular response is time- and
      mycotoxin or mixture-dependent. In particular, after 1h exposure, the DON+ZEA
      combination led to more proteomic changes than DON or ZEA alone, whereas the
      opposite was observed after 24h. In addition, the significant cellular response
      to stress induced by ZEA after 24h exposure seemed to be reduced when combined
      with DON. Thus, these results supported a possible mitigation by the hepatocytes
      when exposed to the mycotoxin mixture for a long duration. These findings
      represent an essential step to further explore adaptive cell response to
      mycotoxin exposure using with more complex incubation kinetics and combining
      different "omics" tools. Moreover, as mycotoxin quantification in cell
      supernatants showed different behaviors for DON and ZEA, this also raises the
      question about how mycotoxins actually trigger the cell response.

PMID- 29208511
TI  - Identification of potent lysophosphatidic acid receptor 5 (LPA5) antagonists as
      potential analgesic agents.
AB  - Lysophosphatidic acid (LPA) plays an important role in a variety of cellular
      functions. In particular, LPA5 receptor is highly expressed in spinal cord and
      dorsal root ganglion, which are associated with pain. This fact prompted us to
      hypothesize that LPA5 antagonists show analgesic effects. To search for potent
      LPA5 antagonists with blood brain barrier (BBB) permeability, we conducted high
      throughput screening (HTS). In HTS campaign, we found a 2H-isoquinoline-1-one
      scaffold showing antagonistic activity against LPA5 and synthesized a series of
      2H-isoquinoline-1-one derivatives and evaluated their LPA5 activities. Among
      these compounds, compound 7e showed potent LPA5 activity with an IC50 value of
      0.12 MUM, and acceptable BBB permeability. Furthermore, it showed effective
      analgesic effect in a chronic constriction injury rat model. Therefore, 7e may
      have a potential as novel pain therapeutic approach.

PMID- 29208512
TI  - Interobserver variability in the delineation of the primary lung cancer and lymph
      nodes on different four-dimensional computed tomography reconstructions.
AB  - PURPOSE: The study compared interobserver variation in the delineation of the
      primary tumour (GTVp) and lymph nodes (GTVln) between three different 4DCT
      reconstruction types; Maximum Intensity Projection (MIP), Mid-Ventilation (Mid-V)
      and Mid-Position (Mid-P). MATERIAL AND METHODS: Seven radiation oncologists
      delineated the GTVp and GTVln on the MIP, Mid-V and Mid-P 4DCT image
      reconstructions of 10 lung cancer patients. The volumes, the mean standard
      deviation (SD) and distribution of SD (SD/area) over the median surface contour
      were compared for different tumour regions. RESULTS: The overall mean delineated
      volume on the MIP was significantly larger (p < 0.001) than the Mid-V and Mid-P.
      For the GTVp the Mid-P had the lowest interobserver variation (SD = 0.261 cm),
      followed by Mid-V (SD = 0.314 cm) and MIP (SD = 0.330 cm) For GTVln the Mid-V had
      the lowest interobserver variation (SD = 0.425 cm) followed by the MIP (SD =
      0.477 cm) and Mid-P (SD = 0.543 cm). The SD/area distribution showed a
      statistically significant difference between the MIP versus Mid-P and Mid-P
      versus Mid-V for both GTVp and GTVln (p < 0.001), with outliers indicating
      interpretation differences for GTVp located close to the mediastinum and GTVln.
      CONCLUSION: The Mid-P reduced the interobserver variation for the GTVp.
      Delineation protocols must be improved to benefit from the improved image quality
      of Mid-P for the GTVln.

PMID- 29208513
TI  - Clinical evaluation of atlas and deep learning based automatic contouring for
      lung cancer.
AB  - BACKGROUND AND PURPOSE: Contouring of organs at risk (OARs) is an important but
      time consuming part of radiotherapy treatment planning. The aim of this study was
      to investigate whether using institutional created software-generated contouring
      will save time if used as a starting point for manual OAR contouring for lung
      cancer patients. MATERIAL AND METHODS: Twenty CT scans of stage I-III NSCLC
      patients were used to compare user adjusted contours after an atlas-based and
      deep learning contour, against manual delineation. The lungs, esophagus, spinal
      cord, heart and mediastinum were contoured for this study. The time to perform
      the manual tasks was recorded. RESULTS: With a median time of 20 min for manual
      contouring, the total median time saved was 7.8 min when using atlas-based
      contouring and 10 min for deep learning contouring. Both atlas based and deep
      learning adjustment times were significantly lower than manual contouring time
      for all OARs except for the left lung and esophagus of the atlas based
      contouring. CONCLUSIONS: User adjustment of software generated contours is a
      viable strategy to reduce contouring time of OARs for lung radiotherapy while
      conforming to local clinical standards. In addition, deep learning contouring
      shows promising results compared to existing solutions.

PMID- 29208514
TI  - Fragmentation level determines mitochondrial damage response and subsequently the
      fate of cancer cells exposed to carbon ions.
AB  - OBJECTIVES: Although mitochondria are known to play an important role in
      radiation-induced cellular damage response, the mechanisms of how radiation
      elicits mitochondrial responses are largely unknown. MATERIALS AND METHODS: Human
      cervical cancer cell line HeLa and human breast cancer cell lines MCF-7 and MDA
      MB-231 were irradiated with high LET carbon ions at low (0.5 Gy) and high (3 Gy)
      doses. Mitochondrial functions, dynamics, mitophagy, intrinsic apoptosis and
      total apoptosis, and survival fraction were investigated after irradiation.
      RESULTS: We found that carbon ions irradiation induced two different
      mitochondrial morphological changes and corresponding responses in cancer cells.
      Cells exposed to carbon ions of 0.5 Gy exhibited only modestly truncated
      mitochondria, and subsequently damaged mitochondria could be eliminated through
      mitophagy. In contrast, mitochondria within cells insulted by 3 Gy radiation
      split into punctate and clustered ones, which were associated with apoptotic cell
      death afterward. Inhibition of mitochondrial fission by Drp1 or FIS1 knockdown or
      with the Drp1 inhibitor mdivi-1 suppressed mitophagy and potentiated apoptosis
      after irradiation at 0.5 Gy. However, inhibiting fission led to mitophagy and
      increased cell survival when cells were irradiated with carbon ions at 3 Gy.
      CONCLUSION: We proposed a stress response model to provide a mechanistic
      explanation for the mitochondrial damage response to high-LET carbon ions.

PMID- 29208515
TI  - Effectiveness of sitagliptin in a patient with late dumping syndrome after total
      gastrectomy.
AB  - An 83-year-old man developed hypoglycemia after undergoing total gastrectomy for
      gastric cancer in 200X-4. The patient was admitted to our hospital in May 200X
      and placed on continuous glucose monitoring (CGM). Glycemic excursions were
      examined while on 3-meal/day (1700kcal) and 6-meal/day (1800kcal) diets.
      Oxyhyperglycemia followed about 2h later by a sudden drop in glucose levels was
      seen with both regimens. These findings were consistent with late dumping
      syndrome. CGM was continued, oral miglitol at 150mg/day or sitagliptin at
      50mg/day was started, and glycemic excursions were compared. Results were similar
      for both drugs, with reductions in postprandial glucose elevations. Meal
      tolerance testing 3 months after oral sitagliptin, compared to before starting
      treatment, showed reductions in both early postprandial hyperglycemia and insulin
      hypersecretion. These findings suggest that DPP-4 inhibitors such as sitagliptin
      may be effective for treating post-gastrectomy late dumping syndrome.

PMID- 29208516
TI  - Selection of the Best of 2017 on Acute Cardiac Care.

PMID- 29208517
TI  - Selection of the Best of 2017 on Cardio-oncology. What Should We Know?

PMID- 29208518
TI  - Three-dimensional Model for Percutaneous Closure of an Iatrogenic Fistula.

PMID- 29208519
TI  - Cardiac Involvement in a Patient With Behcet Disease. Diagnostic and Therapeutic
      Approach.

PMID- 29208520
TI  - Multimodality Imaging in a Patient With Suspected Myocarditis.

PMID- 29208521
TI  - Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4
      hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells.
AB  - Dysfunction or progressive degeneration of retinal pigment epithelium (RPE)
      contributes in the initial pathogenesis of age-related macular degeneration (AMD)
      causing irreversible vision loss, which makes RPE the prime target of the
      disease. The present study aimed to identify compounds to protect 4
      hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4
      (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human
      adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty
      two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were
      synthesized and tested. We found that there was a strong correlation between
      level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell
      death and that of inhibitory activity against 4-HNE-induced superoxide
      production, and that most of the compounds 17 showed minimal DPPH radical
      scavenging activity. Compound 17-28 showed the best protective activity against 4
      HNE-induced superoxide production (79.5% inhibition) and cell death (85.1%
      recovery) at 10 MUM concentration, which was better than that of VAS2870, a
      NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of
      ARPE-19 cells in a concentration-dependent manner. The results indicate that
      compound 17-28 may be a lead compound to develop AMD therapeutics.

PMID- 29208522
TI  - Discovery of new GSK-3beta inhibitors through structure-based virtual screening.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is an attractive therapeutic target
      for human diseases, such as diabetes, cancer, neurodegenerative diseases, and
      inflammation. Thus, structure-based virtual screening was performed to identify
      novel scaffolds of GSK-3beta inhibitors, and we observed that conserved water
      molecules of GSK-3beta were suitable for virtual screening. We found 14 hits and
      D1 (IC50 of 0.71 MUM) were identified. Furthermore, the neuroprotection activity
      of D1-D3 was validated on a cellular level. 2D similarity searches were used to
      find derivatives of high inhibitory compounds and an enriched structure-activity
      relationship suggested that these skeletons were worthy of study as potent GSK
      3beta inhibitors.

PMID- 29208523
TI  - Rational modification of semaxanib and sunitinib for developing a tumor growth
      inhibitor targeting ATP binding site of tyrosine kinase.
AB  - Analysis of the crystal structure of tyrosine kinase in complexation with an ATP
      analogue, supplemented with the molecular docking studies of semaxanib and
      sunitinib in the ATP binding site of the enzyme enabled us to make design of a
      series of tyrosine kinase inhibitors. The combination of pyrrole and indolinone
      in one molecule and placement of appropriate substituent thereof made the
      molecule compatible for the hydrophobic sub-pocket of the enzyme. Screening of
      the compounds over 60 cell line panel of human tumor cell lines identified
      compound 3a that exhibited GI50 35 nM and 63 nM against MCF7 and MDA-MB-468 cell
      lines of breast cancer.

PMID- 29208524
TI  - Synthesis, in vitro alpha-glucosidase inhibitory activity and docking studies of
      novel chromone-isatin derivatives.
AB  - A novel series of chromone-isatin derivatives 6a-6p were designed, synthesized
      and characterized by 1H NMR, 13C NMR and HRMS. These novel synthetic compounds
      were evaluated for inhibitory activity against yeast alpha-glucosidase enzyme.
      The results of biological test have shown that all tested compounds exhibited
      excellent to potent inhibitory activity in the range of IC50 = 3.18 +/- 0.12
      16.59 +/- 0.17 MUM as compared to the standard drug acarbose (IC50 = 817.38 +/-
      6.27 MUM). Compound 6j (IC50 = 3.18 +/- 0.12 MUM) with a hydroxyl group at the 7
      position of chromone and a 4-bromobenzyl group at the N1-positions of isatin, was
      found to be the most active compound among the series. Furthermore, molecular
      docking study was performed to help understand binding interactions of the most
      active analogs with alpha-glucosidase enzyme. These results indicated that this
      class of compounds had potential for the development of anti-diabetic agents.

PMID- 29208525
TI  - Novel familial mutation of LRP5 causing high bone mass: Genetic analysis,
      clinical presentation, and characterization of bone matrix mineralization.
AB  - The Wnt signalling pathway is a critical regulator of bone mass and quality.
      Several heterozygous mutations in the LRP5 gene, a Wnt co-receptor, causing high
      bone mass (LRP5-HBM) have been described to date. The pathogenic mechanism is
      thought to be a gain-of-function caused by impaired inhibition of the canonical
      Wnt signalling pathway, thereby leading to increased bone formation. We report
      the cases of two affected family members, a 53-year-old mother and her 23-year
      old daughter, with high bone mass (T-scores mother: lumbar spine 11.4, femoral
      neck 10.5; T-scores daughter: lumbar spine 5.4, femoral neck 8.7), increased
      calvarial thickness, and thickened cortices of the long bones but no history of
      fractures. Whereas the mother did not show any indications of the mutation, the
      daughter suffered from congenital hearing impairment resulting in cochlear
      implantation, recurrent facial palsy, and migraine. In addition, she had stenosis
      of the foramen magnum. In both individuals, we detected a novel heterozygous
      duplication of six basepairs in the LRP5 gene, resulting in an insertion of two
      amino acids, very likely associated with a gain-of-function. When the daughter
      had part of the occipital bone surgically removed, the bone sample was used for
      the visualization of bone lamellar structure and bone cells as well as the
      measurement of bone mineralization density distribution (BMDD). The bone sample
      revealed two distinctly different regions: an intra-cortical region with osteonal
      remodeling, typical osteonal lamellar orientation, associated with relatively
      higher heterogeneity of bone matrix mineralization, and another periosteal region
      devoid of bone remodeling, with parallel bone lamellae and lower heterogeneity of
      mineralization. In conclusion, we present data on bone tissue and material level
      from an LRP5-HBM patient with a novel mutation in the LRP5 gene. Our findings
      indicate normal morphology of osteoclasts and osteoblasts as well as normal
      mineralization in skull bone in LRP5-HBM.

PMID- 29208527
TI  - Spontaneous pure subacute subdural haematoma without subarachnoid haemorrhage
      caused by rupture of middle cerebral artery aneurysm.

PMID- 29208526
TI  - LARG GEF and ARHGAP18 orchestrate RhoA activity to control mesenchymal stem cell
      lineage.
AB  - The quantity and quality of bone depends on osteoblastic differentiation of
      mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available
      pool for osteogenesis. Cell architecture influences lineage decisions, where
      interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain
      suppresses MSC adipogenesis partially through RhoA driven enhancement of
      cytoskeletal structure. To understand the basis of force-driven RhoA activation,
      we considered critical GEFs (activators) and GAPs (inactivators) on bone marrow
      MSC lineage fate. Knockdown of LARG accelerated adipogenesis and repressed basal
      RhoA activity. Importantly, mechanical activation of RhoA was almost entirely
      inhibited following LARG depletion, and the ability of strain to inhibit
      adipogenesis was impaired. Knockdown of ARHGAP18 increased basal RhoA activity
      and actin stress fiber formation, but did not enhance mechanical strain
      activation of RhoA. ARHGAP18 null MSCs exhibited suppressed adipogenesis assessed
      by Oil-Red-O staining and Western blot of adipogenic markers. Furthermore,
      ARHGAP18 knockdown enhanced osteogenic commitment, confirmed by alkaline
      phosphatase staining and qPCR of Sp7, Alpl, and Bglap genes. This suggests that
      ARHGAP18 conveys tonic inhibition of MSC cytoskeletal assembly, returning RhoA to
      an "off state" and affecting cell lineage in the static state. In contrast, LARG
      is recruited during dynamic mechanical strain, and is necessary for mechanical
      suppression of adipogenesis. In summary, mechanical activation of RhoA in
      mesenchymal progenitors is dependent on LARG, while ARHGAP18 limits RhoA
      delineated cytoskeletal structure in static cultures. Thus, on and off GTP
      exchangers work through RhoA to influence MSC fate and responses to static and
      dynamic physical factors in the microenvironment.

PMID- 29208528
TI  - Heterochromatin protein (HP)1gamma is not only in the nucleus but also in the
      cytoplasm interacting with actin in both cell compartments.
AB  - Confocal and electron microscopy images, and WB analysis of cellular fractions
      revealed that HP1gamma is in the nucleus but also in the cytoplasm of C2C12
      myoblasts, myotubes, skeletal and cardiac muscles, N2a, HeLa and HEK293T cells.
      Signal specificity was tested with different antibodies and by HP1gamma
      knockdown. Leptomycin B treatment of myoblasts increased nuclear HP1gamma,
      suggesting that its nuclear export is Crm-1-dependent. HP1gamma exhibited a
      filamentous pattern of staining partially co-localizing with actin in the
      cytoplasm of myotubes and myofibrils. Immunoelectron microscopic analysis showed
      high-density immunogold particles that correspond to HP1gamma localized to the Z
      disk and A-band of the sarcomere of skeletal muscle. HP1gamma partially co
      localized with actin in C2C12 myotubes and murine myofibrils. Importantly, actin
      co-immunoprecipitated with HP1gamma in the nuclear and cytosolic fractions of
      myoblasts. Actin co-immunoprecipitated with HP1gamma in myoblasts incubated in
      the absence or presence of the actin depolymerizing agent cytochalasin D,
      suggesting that HP1gamma may interact with G-and F-actin. In the cytoplasm,
      HP1gamma was associated to the perinuclear actin cap that controls nuclear shape
      and position. In the nucleus, re-ChIP assays showed that HP1gamma-actin
      associates to the promoter and transcribed regions of the house keeping gene
      GAPDH, suggesting that HP1gamma may function as a scaffold protein for the
      recruitment of actin to control gene expression. When HP1gamma was knocked-down,
      myoblasts were unable to differentiate or originated thin myotubes. In summary,
      HP1gamma is present in the nucleus and the cytoplasm interacting with actin, a
      protein complex that may exert different functions depending on its subcellular
      localization.

PMID- 29208529
TI  - Vesicular transport protein Arf6 modulates cytoskeleton dynamics for polar body
      extrusion in mouse oocyte meiosis.
AB  - Arf6 (ADP-ribosylation factor 6) is known to play important roles in membrane
      dynamics through the regulation of actin filament reorganization for multiple
      cellular processes such as cytokinesis, phagocytosis, cell migration and tumor
      cell invasion. However, the functions of Arf6 in mammalian oocyte meiosis have
      not been clarified. In present study we showed that Arf6 expressed in mouse
      oocytes and was mainly distributed around the spindle during meiosis. Depletion
      of Arf6 by morpholino microinjection caused oocytes failing to extrude first
      polar body. Further analysis indicated that Arf6 knock down caused the aberrant
      actin distribution, which further induced the failure of meiotic spindle
      movement. And the loss of oocyte polarity also confirmed this. The regulation of
      Arf6 on actin filaments in mouse oocytes might be due to its effects on the
      phosphorylation level of cofilin and the expression of Arp2/3 complex. Moreover,
      we found that the decrease of Arf6 caused the disruption of spindle formation,
      indicating the multiple roles of Arf6 on cytoskeleton dynamics in meiosis. In
      summary, our results indicated that Arf6 was involved in mouse oocyte meiosis
      through its functional roles in actin-mediated spindle movement and spindle
      organization.

PMID- 29208530
TI  - Analytical performances of simultaneous detection of HIV-1, HIV-2 and hepatitis C
      specific antibodies and hepatitis B surface antigen (HBsAg) by multiplex
      immunochromatographic rapid test with serum samples: A cross-sectional study.
AB  - BACKGROUND: The HIV/HCV/HBsAg Triplex consists in manually performed, visually
      interpreted, lateral flow, immunochromatographic rapid diagnostic test
      simultaneously detecting in 15min human immunodeficiency virus (HIV)-1 and HIV-2
      and hepatitis C virus (HCV)- specific antibodies (Ab) (IgG and IgM) and hepatitis
      B virus (HBV) surface antigen (HBsAg) in serum, plasma and whole blood. METHODS:
      A hospital-based cross-sectional study was conducted on a prospective panel of
      serum samples from adult inpatients included from routine analysis irrespectively
      of age and sex, including 250 sera positive for HIV-1-specific Ab, 250 for HCV
      specific Ab, 250 for HBsAg and 250 sera negative for HIV- and HCV- Ab and HBsAg,
      and from 110 HIV-2-infected patients living in Ivory Coast, according to the
      results obtained by the reference chemiluminiscent microparticle immunoassay
      (CMIA) Abbott Architect i2000SR analyzer (Abbott Diagnostic, Chicago, IL, USA).
      Among HCV-seropositive sera, 187 were positive for HCV RNA (chronic infection),
      whereas 63 were negative (resolved infection), respectively. Serum samples were
      further tested blindly by HIV/HCV/HBsAg Triplex according to manufacturers'
      recommendations. RESULTS: HIV/HCV/HBsAg Triplex showed very high sensitivity and
      specificity, as well as excellent concordance with CMIA Abbott results, as shown
      in the Table. Lower sensitivity was observed only in individuals who had cleared
      their HCV infection (presence of HCV-specific Ab in absence of HCV RNA). The mean
      lower limit of HBsAg detection was 2.38+/-0.63 IU/ml. Erythrocytes-spiked serum
      samples gave similar results than serum samples. CONCLUSIONS: Advantages of
      HIV/HCV/HBsAg Triplex for HIV-1, HIV-2, HCV and HBV include the requirement for
      less overall specimen volume, fewer finger-sticks if capillary whole blood is
      used, cost savings through lower cost per virus tested, improved patient flow
      with results for multiple viruses available at the same time, overall service
      delivery efficiencies with less time required per infected patient; and patient
      benefits from fewer visits and lower cost associated with each clinic attendance.
      The screening of chronic HIV, HCV and HBV by multiplex HIV-1/HIV-2/HCV/HBsAg
      Triplex may improve the "cascade of screening" and quite possibly linkage-to-care
      with reduced cost.

PMID- 29208531
TI  - The characteristics of household food waste in Hong Kong and their implications
      for sewage quality and energy recovery.
AB  - Food waste (FW) is a worldwide environmental issue due to its huge production
      amount. FW separation from municipal solid waste followed by different treatment
      strategies has been widely accepted. Food waste disposer (FWD) is a promising
      approach to separate and collect household food waste (HFW), which has been
      widely applied in many countries. However, the feasibility of FWD application in
      many countries is still being debated due to the major concerns over the impact
      of FWD on the wastewater treatment plants. In order to investigate the
      feasibility of FWD application, FW characterization is a key work to be conducted
      in advance. Since the FW characteristics largely vary by region, reliable and
      representative FW characteristics in different countries should be investigated.
      To provide such information for further studies on FW management for Hong Kong,
      HFW was collected from Hong Kong typical households over one year and analyzed
      systemically in this study. The FW composition varied little from place to place
      or season to season, and the values observed were comparable with results
      reported from other countries and regions. Based on the reliable HFW
      characteristics obtained from one-year survey coupled with statistical analysis,
      simulated HFW for Hong Kong consisting of 50% fruits, 20% vegetables, 20% starchy
      food and 10% meat was proposed for future studies. On the other hand, the FWD
      treatment caused more than 50% of the biodegradable organic content in HFW to
      dissolve. With a ratio of 1 g food waste to 1 L sewage, total solids in the
      wastewater stream were predicted to increase by 73%, total chemical oxygen demand
      by 61%, soluble chemical oxygen demand by 110%, nitrogen by 6% and phosphorus by
      16%. Theoretically, 22 million m3/year of additional methane could be generated
      if 50% of Hong Kong residential buildings equipped with FWD. That would certainly
      increase pollutant loading on the wastewater treatment plants, but also energy
      recovery potential.

PMID- 29208533
TI  - Assessing cerebellar brain inhibition (CBI) via transcranial magnetic stimulation
      (TMS): A systematic review.
AB  - The inhibitory tone that the cerebellum exerts on the primary motor cortex (M1)
      is known as cerebellar brain inhibition (CBI). Studies show CBI to be relevant to
      several motor functions, including adaptive motor learning and muscle control.
      CBI can be assessed noninvasively via transcranial magnetic stimulation (TMS)
      using a double-coil protocol. Variability in parameter choice and controversy
      surrounding the protocol's ability to isolate the cerebellothalamocortical
      pathway casts doubt over its validity in neuroscience research. This justifies a
      systematic review of both the protocol, and its application. The following review
      examines studies using the double-coil protocol to assess CBI in healthy adults.
      Parameters and CBI in relation to task-based studies, other non-invasive
      protocols, over different muscles, and in clinical samples are reviewed. Of the
      1398 studies identified, 24 met selection criteria. It was found that
      methodological design and selection of parameters in several studies may have
      reduced the validity of outcomes. Further systematic testing of CBI protocols is
      warranted, both from a parameter and task-based perspective.

PMID- 29208532
TI  - Improvement of acidogenic fermentation for volatile fatty acid production from
      protein-rich substrate in food waste.
AB  - Based on our previous study, the low volatile fatty acid (VFA) production from
      egg white in food waste was mainly attributed to more acidogenic substrates
      (proteins and amino acids) consumed in the Maillard reaction and more organics
      converted into lactic acid. In this study, two methods were employed to improve
      VFA production: (1) reducing Maillard reaction with a drop in pH during
      hydrothermal (HT) pretreatment, and (2) inhibiting the conversion from protein to
      lactic acid. HT pretreatment under weakly acidic condition significantly promoted
      the hydrolysis and degradation of protein and the hydrolytic enzyme (protease)
      activity, thus increasing VFA yield by 45.8% from 0.24 to 0.35 g/g protein for HT
      pretreated egg white. Addition of sodium oxamate increased the maximal VFA yield
      from 0.24 to 0.29 g/g protein for HT pretreated egg white and from 0.32 to 0.67
      g/g protein for egg white with no pretreatment in which there was more protein
      converted through the lactic acid metabolism pathway. Sodium oxamate improved the
      acidification step by inhibiting the reaction from pyruvates to lactic acid, and
      thereby accelerating the process of conversion from pyruvates to VFA.

PMID- 29208534
TI  - Loss of CDKL5 disrupts respiratory function in mice.
AB  - Cyclin-dependent kinase-like 5 (CDKL5) is an X-linked gene encoding a serine
      threonine kinase that is highly expressed in the central nervous system.
      Mutations in CDKL5 cause neurological and psychiatric symptoms, including early
      onset seizures, motor dysfunction, autistic features and sleep breathing
      abnormalities in patients. It remains to be addressed whether loss of CDKL5
      causes respiratory dysfunction in mice. Here, we examined the respiratory pattern
      of male Cdkl5-/y mice at 1-3 months of age during resting breathing and
      respiratory challenge (i.e., hypoxia and hypercapnia) via whole body
      plethysmography. The results demonstrated that the resting respiratory frequency
      and tidal volume of Cdkl5-/y mice was unaltered compared to that of WT mice at 1
      month of age. However, these mutant mice exhibit transient reduction in tidal
      volume during respiratory challenge even the reduction was restored at 2 months
      of age. Notably, the sigh-breathing pattern was changed in Cdkl5-/y mice, showing
      a transient reduction in sigh volume at 1-2 month of age and long-term
      attenuation of peak expiratory airflow from 1 to 3 month of age. Therefore, loss
      of CDKL5 causes breathing deficiency, supporting a CDKL5-mediated regulation of
      respiratory function in mice.

PMID- 29208535
TI  - The influence of 5-HT1A receptors in the dorsal raphe nucleus on genioglossus
      activity.
AB  - Genioglossus activity maintains the patency of the upper airway. 5-HT neurons in
      the raphe nucleus regulate genioglossus activity. In order to study the influence
      of 5-HT1A receptors in dorsal raphe nucleus (DRN) on genioglossus EMG during
      normoxia, adult male Wistar rats were randomly divided into four groups: the
      artificial cerebrospinal fluid group (ACSF group), the low-concentration of 5
      HT1A receptors agonist 8-OH-DPAT group (0.1 mM group), the mid-concentration 8-OH
      DPAT group (0.4 mM group) and the high-concentration 8-OH-DPAT group (1.0 mM
      group). Rats received 0.1 MUl ACSF/8-OH-DPAT microinjections into the DRN. EMG
      activity of the genioglossus was recorded at 5 min, 15 min and 30 min after
      microinjection. In three 8-OH-DPAT groups, genioglossus EMG activity
      significantly decreased at 5 min after microinjection and persisted for 30 min.
      The significantly decreased EMG activity was more pronounced in the mid- and high
      concentration groups than in the low-concentration group, indicating that 5-HT1A
      receptors in the DRN could rapidly and continuously inhibit genioglossus EMG
      activity during normoxia.

PMID- 29208536
TI  - HEK-293 secretome attenuates kainic acid neurotoxicity through insulin like
      growth factor-phosphatidylinositol-3-kinases pathway and by temporal regulation
      of antioxidant defense machineries.
AB  - A major impediment in the success of cell therapy for neurodegenerative diseases
      is the poor survival of grafted cells in the in vivo milieu, predominantly due to
      accumulated reactive oxygen species, thus prompting the search for suitable
      alternatives. Accumulating evidence suggests that the therapeutic potential of
      transplanted cells is partially attributed to the secretome released by them into
      the extracellular milieu. Studies that investigated the neuroprotective potential
      of the secretome attributes to the mere presence of growth factors without
      addressing other underlying cellular/molecular changes that occur upon post
      secretome intervention like re-establishing the host cell's free radical
      scavenging machineries. In the present study, we investigated the neuroprotective
      effects of human embryonic kidney (HEK-293) cell line derived secretome (HEK-S)
      in an in vitro model of kainic acid (KA) induced neurodegeneration and explored
      the possible neuroprotective mechanism(s) of HEK-S. Murine hippocampal cells were
      exposed to toxic doses of KA (200MUM) for 6hours (H) or 24H to induce
      excitotoxicity. Kainic acid exposed hippocampal cells were then treated with HEK
      S either simultaneously or 6h post-KA exposure. Our results revealed that HEK-S
      confers significant neuroprotection in early/later stages of neurodegeneration
      through insulin like growth factor (IGF) - phosphatidylinositol-3-kinases (PI3K)
      pathway, efficiently restoring the host's free radical scavenging mechanisms at
      molecular-cellular-biochemical levels and also by modulating kainate receptor
      subunit expressions in host neurons.

PMID- 29208538
TI  - Sleep-Related Painful Erections: A Meta-Analysis on the Pathophysiology and Risks
      and Benefits of Medical Treatments.
AB  - BACKGROUND: Patients with sleep-related painful erections (SRPEs) have frequent
      awakenings from deep penile pain during nocturnal erections. This results in
      severe sleep deprivation. AIM: To review the current literature on SRPEs and
      discuss the pathophysiologic theories and risks and benefits of medical
      treatments. METHODS: PubMed was searched using the terms sleep-related painful
      erections, nocturnal priapism, treatment, and sleep-related erections. OUTCOME:
      Variables included patient demographics, medical history, diagnostics, hypotheses
      on pathophysiology, and treatment modalities and their effect on SRPE in the
      short and long term. RESULTS: The search yielded in 66 SRPE cases that were
      analyzed, including our mono-institutional series of 24 patients. The phenomenon
      of SRPEs is not well understood. Theories about pathophysiology concerned
      increased serum testosterone levels, altered autonomic function, compression of
      the lateral preoptic area, coexistent obstructive sleep apnea syndrome, the
      existence of a "compartment syndrome," and psychosomatic factors. Except for
      polysomnographic findings that showed sleep fragmentation and decreased sleep
      efficiency in all patients, other diagnostic results varied widely. Multiple
      agents were tried. Baclofen and, to lesser degree, clonazepam showed noticeable
      results, most likely due to their influence on the gamma-aminobutyric acid system
      and, hence, suppression of glutamate release. In addition, baclofen relaxes the
      ischiocavernosus and bulbospongiosus muscles, which are involved in penile
      erection. CLINICAL IMPLICATIONS: By providing a critical analysis and complete
      overview on the limited literature about this overlooked and undermanaged
      condition, this review contributes to a better understanding of the
      pathophysiology and provides directions for future research on the treatment of
      SRPE. STRENGTHS AND LIMITATIONS: Because the literature on SRPEs includes only
      case reports and small case series, the level of evidence of treatment advice is
      limited. CONCLUSION: The pathophysiology of SRPEs is not yet clarified. Further
      diagnostic evaluation, including electromyography of the ischiocavernosus and
      bulbospongiosus muscles to elucidate the pathophysiology, is recommended.
      Prospective controlled investigations are warranted to assess the efficacy and
      safety of long-term use of baclofen and develop evidence-based treatment advice.
      Vreungdenhil S, Weidenaar AC, de Jong IJ, van Driel MF. Sleep-Related Painful
      Erections: A Meta-Analysis on the Pathophysiology and Risks and Benefits of
      Medical Treatments. J Sex Med 2018;15:5-19.

PMID- 29208537
TI  - Comprehensive Evaluation of the Learning Curve for Peroral Endoscopic Myotomy.
AB  - BACKGROUND & AIMS: Peroral endoscopic myotomy (POEM) is a minimally invasive
      endoscopic surgical procedure that is effective in treatment for spastic
      esophageal motility disorders. However, little is known about the learning curve
      for endoscopists. We aimed to evaluate the effects of various factors on the POEM
      learning curve. METHODS: We performed a retrospective study of 1346 patients who
      underwent POEM for achalasia at Shanghai Zhongshan Hospital in China from August
      2010 through July 2015. We used risk-adjusted cumulative sum and moving average
      methods to evaluate outcomes. The primary outcome was a composite of technical
      failure and adverse events. Secondary outcomes included procedure time and the
      composite outcome of technical failure, adverse events, and clinical failure of
      the first 192 cases performed by only the original, training surgeon. RESULTS:
      The primary composite outcome occurred in 54 (4%) of the 1346 patients: 10
      technical failures and 44 adverse events. This composite outcome was
      independently associated with the case number (P = .010), full-thickness myotomy
      (P = .002), and procedure time (P = .001). After we adjusted for these risk
      factors, cumulative sum analysis showed that the primary composite outcome
      decreased gradually after 100 cases. The procedure time was high during the first
      few cases and decreased after endoscopists performed 70 cases. The secondary
      composite outcome of technical failure, adverse events, and clinical failure for
      the 192 cases performed by only the original surgeon gradually decreased after 90
      100 cases. CONCLUSIONS: In a retrospective analysis of POEM procedures, we found
      that 100 cases were required to decrease the risk of technical failure, adverse
      events, and clinical failure (the learning curve). Seventy cases can be
      considered the threshold for decreasing procedure time.

PMID- 29208539
TI  - Trichoderma based synthesis of anti-pathogenic silver nanoparticles and their
      characterization, antioxidant and cytotoxicity properties.
AB  - Antibacterial silver nanoparticles (AgNPs) are synthesized from various
      biological resources, but studies on Trichoderma-based synthesis are limited.
      Hence, the current work synthesized antibacterial silver nanoparticles using
      Trichoderma atroviride and also tested for their biomedical properties. AgNPs
      synthesis was confirmed by the occurrence of plasmon resonance at 390-400 nm in
      the UV-vis spectrum. FTIR spectrum displayed the bands at 1115.4 and 3450 cm-1
      indicating the vibrations of the metallic oxides. Transmission electron
      microscopic and EDX analysis confirmed a high percentage signal of anisotropic
      structural AgNPs with the size of 15-25 nm. The AgNPs exhibited high
      antibacterial activity and DPPH scavenging activity in a dosedependent manner.
      The cytotoxicity assay ???? indicated that the AgNPs triggered the cancer cell
      death at the inhibitory concentration of IC50 16.5 MUg/ml. Current work reported
      for the first time Trichoderma atroviride based synthesis of anisotropic
      structural AgNPs with the relatively small size of 15-25 nm with remarkable anti
      bacterial, antioxidant and cytotoxicity activities, and this deserves future
      investigations for biomedical applications.

PMID- 29208540
TI  - Phytochemical analysis and antibacterial activities extracts of mangrove leaf
      against the growth of some pathogenic bacteria.
AB  - In this study, the effects of water, ethanol, methanol and glycerin at five
      levels (0, 31.25, 83.33, 125 and 250 ml) were investigated on the efficiency of
      mangrove leaf extraction using mixture optimal design. The antimicrobial effect
      of the extracts on Streptococcus pneumoniae, Enterococcus faecium and Klebsiella
      pneumoniae was evaluated using disk diffusion, minimum inhibitory concentration
      (MIC) and minimum bactericidal concentration (MBC) methods. The mangrove leaf
      extraction components were identified through gas chromatography/mass
      spectrometry (GC/MS). Phytochemical analysis (alkaloids, tannins, saponins,
      flavone and glycosides) were evaluated based on qualitative methods. Antioxidant
      activity of extracts was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      ferric reducing antioxidant potential (FRAP) methods. Maximum antimicrobial
      effect was observed in Enterococcus faecium and highest resistance against
      mangrove leaf extract in Enterococcus faecium and Klebsiella pneumoniae,
      respectively. Increasing concentration of mangrove extracts had a significant
      effect (p <= 0.05) on inhibition zone diameter. The MICs of the mangrove leaf
      extraction varied from 4 mg/ml to 16 mg/ml. The optimum formulation was found to
      contain glycerin (0 ml), water (28.22 ml), methanol (59.83 ml) and ethanol
      (161.95 ml). The results showed that the highest antioxidant activity was related
      to optimum extract of mangrove leaf and ethanolic extract respectively. The
      results of phytochemical screening of Avicennia marina leaves extract showed the
      existence of alkaloids, tannins, saponins, flavone and glycosides. 2-Propenoic
      acid, 3-phenyl- was the major compound of Avicennia marina. The results of non
      significant lack of fit tests, and F value (14.62) indicated that the model was
      sufficiently accurate. In addition, the coefficient of variations (16.8%) showed
      an acceptable reproducibility.

PMID- 29208541
TI  - Biological synthesis of silver nanoparticles using beta-1, 3 glucan binding
      protein and their antibacterial, antibiofilm and cytotoxic potential.
AB  - The present study reports the biological synthesis of silver nanoparticles using
      crustacean immune molecule beta-1, 3 glucan binding protein (beta-GBP) purified
      from the haemolymph of blue swimmer crab Portunus pelagicus. The characterization
      of synthesized beta-GBP based silver nanoparticles (Ppbeta-GBP-AgNPs) was made by
      UV-Vis spectroscopy, XRD, FTIR and TEM analysis. UV-Vis spectra recorded the
      strong absorbance peak at 420 nm due to its surface plasmon resonance. The XRD
      analysis revealed the crystalline nature of synthesized nanoparticles with
      Bragg's reflection peaks at (111), (200), (220), (311) planes. FTIR analysis
      showed the possible functional groups at 3422, 2926, 2847, 1648, 1556, 1407, 1016
      and 669 cm-1. The mean particle size of Ppbeta-GBP-AgNPs was 33-47 nm revealed by
      TEM analysis. Ppbeta-GBP-AgNPs exhibit appreciable antibacterial activity against
      Enterococcus faecalis and Pseudomonas aeruginosa when compared to chemical based
      AgNPs (Chem-AgNPs). The antibiofilm property of Ppbeta-GBP-AgNPs was assessed
      through light microscopy and confocal laser scanning microscopy analysis (CLSM),
      which clearly demonstrates, thickness of E. faecalis and P. aeruginosa preformed
      biofilm was reduced to 11 MUm & 8 MUm from 47 MUm & 45 MUm respectively.
      Moreover, exopolysaccharide (EPS) quantification and cell surface hydrophobicity
      (CSH) index exhibited that, Ppbeta-GBP-AgNPs had the potential to disturb
      structural integrity of biofilm by upset EPS matrix and bacterial adhesion to
      hydrocarbons. In addition, the cytotoxic effect of Ppbeta-GBP-AgNPs was evaluated
      against human cervical cancer cells (HeLa). Ppbeta-GBP-AgNPs effectively inhibit
      the viability of HeLa cells at 50 MUg/ml concentration and the morphological
      changes in Ppbeta-GBP-AgNPs treated HeLa cells were observed under phase contrast
      microscopy.

PMID- 29208542
TI  - Antibiotics susceptibility of quinolones against Salmonella spp. strains isolated
      and molecularly sequenced for gyrA gene.
AB  - Drug-resistant Salmonella is frequently detected in most parts of the world, and
      its rate of resistance has increased significantly in recent years. However, this
      study aimed to evaluate the minimum inhibitory concentration (MIC, determined
      with the Kirby-Bauer method) of quinolones in 86 Salmonella spp. strains isolated
      from pigs. Both the inside and outside of the QRDR region of strains were
      sequenced. The DNA sequence of the QRDR region of Salmonella spp. revealed the
      mutations S83F, D87N and S83Y. The region outside the QRDR showed a mutation in
      L582G. Forty-five isolates of Salmonella ssp. were categorized as quinolone
      resistant; out of these, 16 corresponded to Salmonella enterica and isolates
      showed intermediate resistance (6.25%) to nalidixic acid. Three isolats (18.6%)
      were resistant to ampicillin; two (12.5%) were resistant to carbenicillin.
      Moreover, three (18.7%) isolates were resistant to gentamicin, nitrofurantoin and
      pefloxacin, and 8 (50%) were resistant to trimethoprim/sulfamethoxazole. Six
      percent of Salmonella spp. strains showed less resistance to antimicrobial agents
      compared to S. Thyphimurium (18%). The resistance to individual quinolones varied
      by serotypes. For S. anatum and S. Reading, it was 12.25%, and for S.
      choreaeaesuis, S. typhimurium monofasica, 6.25%. In contrast, S. agona, S.
      bredeney and S. london were sensitive to these antibiotics. In conclusion,
      quinolones have become the drugs of choice for the treatment of severe Salmonella
      infections. The study of mutations outside the QRDR region opens up new insights
      about the resistance of Salmonella to fluoroquinolones.

PMID- 29208543
TI  - In vivo toxic effects of 4-methoxy-5-hydroxy-canthin-6-one in zebrafish embryos
      via copper dyshomeostasis and oxidative stress.
AB  - Dysfunction of copper homeostasis can lead to a host of disorders, which might be
      toxic sometimes. 4-Methoxy-5-hydroxy-canthin-6-one (CAN) is one of the major
      constituents from Picrasma quassioides and responsible for its therapeutic
      effects. In this work, we evaluated the toxic effect of CAN (7.5MUM) on zebrafish
      embryos. CAN treatment decreased survival, delayed hatching time and induced
      malformations (loss of pigmentation, pericardial edema, as well as hematologic
      and neurologic abnormalities). Besides, exogenous copper supplementation rescued
      the pigmentation and cardiovascular defects in CAN-treated embryos. Further
      spectroscopic studies revealed a copper-chelating activity of CAN. Then its
      regulation on the expressions of copper homeostasis related genes also be
      analyzed. In addition, CAN lowered the total activity of SOD, elevated the ROS
      production and altered the oxidative related genes transcriptions, which led to
      oxidative stress. In conclusion, we demonstrated that CAN (7.5MUM) might exert
      its toxic effects in zebrafish embryos by causing copper dyshomeostasis and
      oxidative stress. It will give insight into the risk assessment and prevention of
      CAN-mediated toxicity.

PMID- 29208544
TI  - Mandibuloacral dysplasia: A premature ageing disease with aspects of
      physiological ageing.
AB  - Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone
      abnormalities including localized osteolysis and generalized osteoporosis, skin
      pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular
      defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene,
      causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24
      mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects
      chromatin dynamics and stress response. A new form of mandibuloacral dysplasia
      has been recently associated with mutations in POLD1 gene, encoding DNA
      polymerase delta, a major player in DNA replication. Of note, involvement of
      prelamin A in chromatin dynamics and recruitment of DNA repair factors has been
      also determined under physiological conditions, at the border between stress
      response and cellular senescence. Here, we review current knowledge on MAD
      clinical and pathogenetic aspects and highlight aspects typical of physiological
      ageing.

PMID- 29208545
TI  - IL-24 is a common and specific autoantigen of IgE in patients with chronic
      spontaneous urticaria.
AB  - BACKGROUND: The efficacy of omalizumab (anti-IgE) and increased IgE levels in
      patients with chronic spontaneous urticaria (CSU) suggest autoallergic
      mechanisms. OBJECTIVE: We sought to identify autoallergic targets of IgE in
      patients with CSU. METHODS: Serum samples of patients with CSU together with
      those of patients with idiopathic anaphylaxis and healthy control subjects (7 of
      each) were screened for IgE autoantibodies by using an array of more than 9000
      proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were
      used in an IgE-anti-IL-24-specific ELISA to investigate the association of IgE
      anti-IL-24 and CSU. RESULTS: By using array analyses, more than 200 IgE
      autoantigens were found in patients with CSU that were not found in control
      subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8
      were soluble or membrane bound and expressed in the skin. Of these, only IgE
      autoantibodies to IL-24 were found in all patients with CSU. In vitro studies
      showed IL-24 to release histamine from human mast cells sensitized with purified
      IgE of patients with CSU but not control subjects. By using ELISA, mean +/- SD
      levels of IgE-anti-IL-24 were 0.52 +/- 0.24 IU/mL in patients with CSU and 0.27
      +/- 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of
      control subjects having levels greater than 0.33 IU/mL (P < .0001). IgE-anti-IL
      24 showed acceptable predictive properties for CSU, with a likelihood ratio of
      3.9. Clinically, IgE-anti-IL-24 levels showed an association with disease
      activity, as assessed by the urticaria activity score and with reduced basophil
      counts. CONCLUSION: Our findings show that patients with CSU frequently exhibit
      IgE autoantibodies against many autoantigens and that IL-24 is a common,
      specific, and functional autoantigen of IgE antibodies in patients with CSU.

PMID- 29208546
TI  - Thymic stromal lymphopoietin does not activate human basophils.

PMID- 29208547
TI  - Generation of adult human T-cell progenitors for immunotherapeutic applications.

PMID- 29208548
TI  - Physicians infrequently miss choledocholithiasis prior to cholecystectomy in the
      United States.

PMID- 29208549
TI  - The natural history of achalasia: Evidence of a continuum-"The evolutive pattern
      theory".
AB  - BACKGROUND: It is currently unclear if the three manometric patterns of
      esophageal achalasia represent distinct entities or part of a disease continuum.
      The study's aims were: a) to test the hypothesis that the three patterns
      represent different stages in the evolution of achalasia; b) to investigate
      whether manometric patterns change after Laparoscopic-Heller-Dor (LHD). METHODS:
      We assessed the patients diagnosed with achalasia who underwent LHD as their
      first treatment from 1992 to 2016. Their symptoms were scored using a detailed
      questionnaire for dysphagia, food-regurgitation, and chest pain. Barium-swallow,
      endoscopy, and esophageal-manometry were performed before and 6 months after
      surgery. RESULTS: The study population consisted of 511 patients (M:F=283:228).
      Patients' demographic and clinical data showed that those with pattern III had a
      shorter history of symptoms, a higher incidence of chest pain, and a less dilated
      gullet (p<0.001). All patients with a sigmoid-shaped mega-esophagus had pattern I
      achalasia. One patient with a diagnosis of pattern III achalasia developed
      pattern II at a follow-up manometry before surgery. At a median follow-up of 30
      months (IQR 12-56), the outcome of surgery was positive in 479 patients (91.7%).
      All patients with pattern I preoperatively had the same pattern after LHD,
      whereas more than 50% of patients with pattern III before treatment showed
      pattern I or II after surgery. CONCLUSIONS: This study supports the
      hypothesis/theory that the different manometric patterns represent different
      stages in the evolution of the disease-where pattern III is the earliest stage,
      pattern II an intermediate stage, and pattern I the final stage.

PMID- 29208550
TI  - Transabdominal salvage surgery after pouch failure in a tertiary center: A case
      matched study.
AB  - BACKGROUND: Salvage surgery after failure of ileal pouch-anal anastomosis (IPAA)
      could be offered to selected patients. However, the results vary widely in
      different centers. AIMS: To assess the outcomes of salvage surgery by comparison
      with a control group matched for confounding variables. METHODS: From a
      prospective database of 1286 IPAA, patients undergoing transabdominal salvage
      surgery were compared for perioperative and functional outcomes and quality of
      life (QOL) to a 1:3 control group of primary IPAA cases. RESULTS: Salvage surgery
      patients (30) had a higher rate of hand-sewn anastomoses (80 vs 20%, p <0.0001)
      and reoperations (10 vs 2.2%, p 0.02) than control group (90). A higher number of
      daytime and nighttime bowel movements (7.4 vs 4.1, p <0.0001, and 2.6 vs 1.8,
      p=0.002), a lower median CGQL score (0.7 vs 0.8, p=0.0001) and a higher rate of
      pouch fistulae (13.3 vs 1.1%, p=0.003) were reported after salvage surgery. Pouch
      failure rate after salvage surgery was 10.1%, 18.7% and 26.8% at 1, 5 and 10
      years (vs 0%, 3.5% and 8.4% in control group, p=0.0085). CONCLUSIONS: Although
      worse functional outcomes and decreased QOL have to be expected, salvage surgery
      after pouch failure is associated with acceptable outcomes when performed in a
      referral center.

PMID- 29208551
TI  - A simplified prognostic model to predict mortality in patients with acute
      variceal bleeding.
AB  - BACKGROUND: Acute variceal bleeding (AVB) is a major cause of death in patients
      with liver cirrhosis. The aim of this study was to investigate mortality
      predictors and develop a new simple prognostic model using easily verified
      factors at admission in AVB patients. METHODS: Between January 2009 and May 2015,
      333 consecutive patients with AVB were included. A simplified prognostic model
      was developed using multiple logistic regression after identifying significant
      predictors of 6-week mortality. Mortality prediction accuracy was assessed with
      area under the receiver operating characteristic (AUROC) curve. We compared the
      new model to existing models of model for end-stage liver disease (MELD) and
      Child-Pugh scores. RESULTS: The 6-week overall mortality rate was 12.9%.
      Multivariate analysis showed that C-reactive protein (CRP), total bilirubin, and
      the international normalized ratio were independent predictors of mortality. A
      new logistic model using these variables was developed. This model's AUROC was
      0.834, which was significantly higher than that of MELD (0.764) or Child-Pugh
      scores (0.699). Two external validation studies showed that the AUROC of our
      model was consistently higher than 0.8. CONCLUSIONS: Our new simplified model
      accurately and consistently predicted 6-week mortality in patients with AVB using
      objective variables measured at admission. Our system can be used to identify
      high risk AVB patients.

PMID- 29208552
TI  - Controlling human corneal stromal stem cell contraction to mediate rapid cell and
      matrix organization of real architecture for 3-dimensional tissue equivalents.
AB  - : The architecture of the human corneal stroma consists of a highly organized
      extracellular matrix (ECM) interspersed with keratocytes. Their progenitor cells;
      corneal stromal stem cells (CSSC) are located at the periphery, in the limbal
      stroma. A highly organized corneal ECM is critical for effective transmission of
      light but this structure may be compromised during injury or disease, resulting
      in loss of vision. Re-creating normal organization in engineered tissue
      equivalents for transplantation often involves lengthy culture times that are
      inappropriate for clinical use or utilisation of synthetic substrates that bring
      complications such as corneal melting. CSSC have great therapeutic potential
      owing to their ability to reorganize a disorganized matrix, restoring
      transparency in scarred corneas. We examined CSSC contractile behavior to assess
      whether this property could be exploited to rapidly generate cell and ECM
      organization in Real Architecture For 3D Tissues (RAFT) tissue equivalents (TE)
      for transplantation. Free-floating collagen gels were characterized to assess
      contractile behavior of CSSC and establish optimum cell density and culture
      times. To mediate cell and collagen organization, tethered collagen gels seeded
      with CSSC were cultured and subsequently stabilized with the RAFT process. We
      demonstrated rapid creation of biomimetic RAFT TE with tunable structural
      properties. These displayed three distinct regions of varying degrees of cellular
      and collagen organization. Interestingly, increased organization coincided with a
      dramatic loss of PAX6 expression in CSSC, indicating rapid differentiation into
      keratocytes. The organized RAFT TE system could be a useful bioengineering tool
      to rapidly create an organized ECM while simultaneously controlling cell
      phenotype. STATEMENT OF SIGNIFICANCE: For the first time, we have demonstrated
      that human CSSC exhibit the phenomenon of cellular self-alignment in tethered
      collagen gels. We found this mediated rapid co-alignment of collagen fibrils and
      thus subsequently exploited this property in vitro to improve the architecture of
      engineered RAFT tissue equivalents of the corneal stroma. Existing techniques are
      extremely lengthy and carry significant risk and cost for GMP manufacture. This
      rapid and tunable technique takes just 8 h of culture and is therefore ideal for
      clinical manufacture, creating biomimetic tissue equivalents with both cellular
      and ECM organization. Thus, cellular self-alignment can be a useful
      bioengineering tool for the development of organized tissue equivalents in a
      variety of applications.

PMID- 29208553
TI  - Fibril growth kinetics link buffer conditions and topology of 3D collagen I
      networks.
AB  - : Three-dimensional fibrillar networks reconstituted from collagen I are widely
      used as biomimetic scaffolds for in vitro and in vivo cell studies. Various
      physicochemical parameters of buffer conditions for in vitro fibril formation are
      well known, including pH-value, ion concentrations and temperature. However,
      there is a lack of a detailed understanding of reconstituting well-defined 3D
      network topologies, which is required to mimic specific properties of the native
      extracellular matrix. We screened a wide range of relevant physicochemical buffer
      conditions and characterized the topology of the reconstituted 3D networks in
      terms of mean pore size and fibril diameter. A congruent analysis of fibril
      formation kinetics by turbidimetry revealed the adjustment of the lateral growth
      phase of fibrils by buffer conditions to be key in the determination of pore size
      and fibril diameter of the networks. Although the kinetics of nucleation and
      linear growth phase were affected by buffer conditions as well, network topology
      was independent of those two growth phases. Overall, the results of our study
      provide necessary insights into how to engineer 3D collagen matrices with an
      independent control over topology parameters, in order to mimic in vivo tissues
      in in vitro experiments and tissue engineering applications. STATEMENT OF
      SIGNIFICANCE: The study reports a comprehensive analysis of physicochemical
      conditions of buffer solutions to reconstitute defined 3D collagen I matrices. By
      a combined analysis of network topology, i.e., pore size and fibril diameter, and
      the kinetics of fibril formation we can reveal the dependence of 3D network
      topology on buffer conditions, such as pH-value, phosphate concentration and
      sodium chloride content. With those results we are now able to provide
      engineering strategies to independently tune the topology parameters of widely
      used 3D collagen scaffolds based on the buffer conditions. By that, we enable the
      straightforward mimicking of extracellular matrices of in vivo tissues for in
      vitro cell culture experiments and tissue engineering applications.

PMID- 29208555
TI  - Hollow mesoporous zirconia delivery system for biomineralization precursors.
AB  - : Strategies based on the combination of nanocarrier delivery systems and
      scaffolds provide bone tissue engineering scaffolds with multifunctional
      capability. Zirconia, a biocompatible ceramic commonly used in orthopedic and
      dental implants, was used to synthesize hollow mesoporous nanocapsules for
      loading, storage and sustained release of a novel polyamine-stabilized liquid
      precursor phase of amorphous calcium phosphate (PAH-ACP) for collagen
      biomineralization and bone marrow stromal cells osteoinduction. Hollow mesoporous
      zirconia (hmZrO2) nanocapsules loaded with biomimetic precursors exhibited pH
      sensitive release capability and good biocompatibility. The PAH-ACP released from
      loaded hmZrO2 still retained the ability to infiltrate and mineralize collagen
      fibrils as well as exhibited osteoinductivity. A collagen scaffold blended with
      PAH-ACP@hmZrO2 supplement and stem cells may be a promising tool for bone tissue
      engineering. STATEMENT OF SIGNIFICANCE: The advent of nanotechnology has
      catalyzed the development of bone tissue engineering strategies based on the
      combination of nanocarrier delivery systems and scaffolds, which provide distinct
      advantages, including the possibilities of sustained release and protection of
      the bioactive agents, site-specific pharmacological effects and reduction of side
      effects. Herein, hollow mesoporous zirconia (hmZrO2) nanocapsules with pH
      sensitive capacity were synthesized for loading, storage and sustained release of
      a novel polyamine-stabilized liquid precursor phase of ACP (PAH-ACP). The loaded
      nanocapsules show good biocompatibility and demonstrate bioactivities for
      collagen biomineralization and bone marrow stromal cells osteoinduction. Our
      results may offer a promising tool for designing bone tissue engineering
      "cocktail therapy" involving seeding scaffolds with biomineralization precursors
      loaded hmZrO2 supplement and stem cells.

PMID- 29208554
TI  - Intracutaneous delivery of gelatins induces lipolysis and suppresses lipogenesis
      of adipocytes.
AB  - Due to growing interest in cosmetics and medical applications, therapeutic
      medications that reduce the amount of local subcutaneous adipose tissue have
      potential for obesity treatment. However, conventional methods such as surgical
      operation are restricted due to risk of complications. Here, we report a simple
      and effective method for local reduction of subcutaneous adipose tissue (AT) by
      using microneedle-assisted transdermal delivery of natural polymers. After in
      vitro screening tests, gelatin was selected as a therapeutic polymer to reduce
      accumulation of AT. An in vitro study showed that the level of released glycerol
      as an indicator of lipolysis was elevated in isolated adipocytes after gelatin
      treatment. In addition, gelatins suppressed expression levels of lipogenesis
      associated genes. Following application of gelatin microneedle (GMN) patches to
      high-fat diet (HD)-induced obese rats, the amount of subcutaneous AT at the site
      of GMN application was significantly reduced, which was also confirmed by
      histological analysis and micro-computed tomography scanning. In addition,
      lipogenesis-associated genes were down-regulated in GMN-treated subcutaneous AT.
      These findings suggest that GMN patches induce lipolysis and simultaneously
      inhibit lipogenesis, thereby reducing deposition of subcutaneous AT. This
      platform using GMNs may provide a new strategy to treat excess subcutaneous AT
      with minimal complications. STATEMENT OF SIGNIFICANCE: (1) Significance This work
      reports a new approach for the local reduction of subcutaneous adipose tissue
      using a dissolving microneedle patch prepared using gelatin to enable suppression
      of lipogenesis and acceleration of lipolysis in adipocytes. The gelatin
      microneedle patch exhibited a significant reduction of local subcutaneous fat up
      to 60% compared to control groups without any change in total weight. (2)
      Scientific impact This is the first report demonstrating the direct anti-obesity
      effects of gelatin administrated in a transdermal route and the feasibility of
      natural polymer therapeutics for regional reduction of subcutaneous fat. We
      believe that our work will excite interdisciplinary readers of Acta
      Biomaterialia, those who are interested in the natural polymers, drug delivery,
      and obesity.

PMID- 29208556
TI  - Binding of thioflavin T by albumins: An underestimated role of protein oligomeric
      heterogeneity.
AB  - Amyloid fibrils formation is the well-known hallmark of various neurodegenerative
      diseases. Thioflavin T (ThT)-based fluorescence assays are widely used to detect
      and characterize fibrils, however, if performed in bioliquids, the analysis can
      be biased due to the presence of other, especially abundant, proteins.
      Particularly, it is known that albumin may bind ThT, although the binding
      mechanism remains debatable. Here the role of low-order albumin oligomers in ThT
      binding is investigated using time-resolved fluorometry and size-exclusion
      chromatography. Under conditions used, the fraction of dimers in human (HSA) and
      bovine (BSA) serum albumin solutions is as low as ~7%, however, it is responsible
      for ~50% of ThT binding. For both albumins, the binding affinity was estimated to
      be ~200 and ~40MUM for monomeric and dimeric species, respectively. Molecular
      docking suggested that ThT preferentially binds in the hydrophobic pocket of
      subdomain IB of albumin monomer in a similar position but with a variable torsion
      angle, resulting in a lower fluorescence enhancement (~40-fold) compared to
      amyloid fibrils (~1000-fold). Dimerization of albumin presumably creates an extra
      binding site at the subunit interface. These results demonstrate the
      underestimated role of low-order albumin oligomers that can be highly relevant
      when analyzing drugs binding using fluorescence spectroscopy.

PMID- 29208557
TI  - Demonstration of bioprocess factors optimization for enhanced mono-rhamnolipid
      production by a marine Pseudomonas guguanensis.
AB  - We identified that Pseudomonas guguanensis produced macromolecular mono
      rhamnolipid (1264.52 Da) upon sensing n-hexadecane/diesel/kerosene from its
      surroundings. Permutation experiments were done to improve the laboratory-scale
      mono-rhamnolipid production (ie, a three-fold increase) using RSM validation.
      Consequently, maximal mono-rhamnolipids production [40-50 mg/L] and
      emulsification abilities [65-70%] were encountered on day 8 using vegetable oil,
      peptone + yeast extract. EI24 values for the rhamnolipids were found to be 78+/
      1.75% at 12.5 mg/ mL. Production and secretion of rhamnolipids were accompanied
      by aggregation of cells at day 6 as pictured in SEM. Pure monorhamnolipids of P.
      guguanensis was found to lower the surface tension of water to 32.98+/-0.3 mN/m
      than the crude and CFSs of P. aeruginosa indicating efficient activity.
      Utilization and subsequent removal of hexadecane was 77.2% and the breakdown
      products were fatty acids [decanoic, hexadecanoic, octadecanoic acids and methyl
      stearates] as signified in Head-space GC-MS. The breakdown products of hexadecane
      are also present in the synthesized rhamnolipids suggesting their biosynthetic
      role. Rapid degradation of hexadecane, diesel and kerosene by this emulsifier
      combined with non-pathogenic trait of P. guguanensis identifies this organism as
      a viable option to remove n-alkanes from aquatic environments.

PMID- 29208558
TI  - Aggregation of globular protein as a consequences of macromolecular crowding: A
      time and concentration dependent study.
AB  - The living cells show profoundly crowded condition, called as macromolecular
      crowding. Crowding essentially impacts on protein structure and lead to its
      aggregation. Protein aggregates have been involved in a wide range of diseases
      including Parkinson, Alzheimer's, and Huntington's. Increased in normal
      physiological macromolecular crowding because of increasing age can be implicated
      as one of the leading cause of proteopathies. In the present study, we have
      demonstrated the effect of macromolecular crowding on native structure of
      hemoglobin using bovine serum albumin as a crowding agent. Conformational changes
      of Hb at different concentrations of BSA were monitored using intrinsic
      fluorescence and ATR-FTIR spectroscopy. These results showed the transition of
      native Hb to a non-native form. Thermodynamic parameters were analyzed by
      isothermal titration calorimetry. The measurements of turbidity, thioflavin T,
      congo red and intrinsic fluorescence revealed the formation of significant
      protein aggregates with time. The kinetics of protein aggregation using relative
      ThT and 8-anilino-1-naphthalenesulphonic acid spectra clearly showed acceleration
      of the process with time and in concentration dependent manner. The spectra at
      80g/l of BSA incubated for 64h showed formation of maximum Hb aggregates.
      Transmission electron microscopy results clearly showed the formation of amyloid
      aggregates structures, thus supporting the spectroscopic data.

PMID- 29208559
TI  - Pilose antler peptide attenuates LPS-induced inflammatory reaction.
AB  - The present study was designed to study the effects of pilose antler peptide
      (PAP) on primary culture of nucleus pulposus cells in intervertebral disc. We
      demonstrated that PAP significantly inhibited lipopolysaccharides (LPS) induced
      over-production of inflammatory factors including interleukin-1beta (IL-1beta),
      tumor necrosis Factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in nucleus
      pulposus cells. PAP also attenuated increase of malondialdehyde (MDA) and
      decrease of superoxide dismutase (SOD) induced by LPS challenge in a
      concentration-dependent manner. Moreover, the expression of the protein levels of
      mitogen-activated protein kinase (MAPK)/nuclear transcription factor-kappaB(NF
      kappaB) were increased accompanying with the LPS challenge, which were
      significantly reversed after PAP treatment. Our results demonstrated the ability
      of PAP to antagonize LPS-mediated inflammation in primary culture of nucleus
      pulposus in intervertebral disc, suggesting a beneficial potential for its
      clinical application.

PMID- 29208560
TI  - Multiplex PCR system for the rapid diagnosis of respiratory virus infection:
      systematic review and meta-analysis.
AB  - OBJECTIVES: To provide a summary of evidence for the diagnostic accuracies of
      three multiplex PCR systems (mPCRs)-BioFire FilmArray RP (FilmArray), Nanosphere
      Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays-on the
      detection of viral respiratory infections. METHODS: A comprehensive search up to
      1 July 2017 was conducted on Medline and Embase for studies that utilized
      FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory
      infections. A summary of diagnostic accuracies for the following five viruses
      were calculated: influenza A virus (FluA), influenza B virus, respiratory
      syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary
      receiver operating curves were used for estimating the viral detection
      performance per assay. RESULTS: Twenty studies of 5510 patient samples were
      eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with
      area under the receiver operating characteristic curve (AUROC) equal to or more
      than 0.98 for all the above viruses except for adenovirus (AUROC 0.89).
      FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data)
      demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval,
      0.848-0.949), 0.949 (95% confidence interval, 0.882-0.979) and 0.954 (95%
      confidence interval, 0.871-0.985), respectively. The three mPCRs were comparable
      in terms of detection of FluA. CONCLUSIONS: Point estimates calculated from
      eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and
      ProFlu+) are highly accurate and may provide important diagnostic information for
      early identification of respiratory virus infections. In patients with low
      pretest probability for FluA, these three mPCRs can predict a low possibility of
      infection and may justify withholding empirical antiviral treatments.

PMID- 29208561
TI  - Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma
      and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi
      experimental single-centre before-after study.
AB  - OBJECTIVES: We aimed to study whether ciprofloxacin prophylaxis reduces
      infectious complications in patients undergoing autologous haematopoietic cell
      transplantation (AHCT). METHODS: This is a quasi-experimental, retrospective,
      before-after study. We compared the incidence of bacterial-related complications
      among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154)
      who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis
      between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a
      single centre. RESULTS: Febrile neutropaenia, bacteraemia, and pneumonia were
      significantly more common among patients who underwent AHCT during the second
      study period and did not receive antibacterial prophylaxis compared with patients
      who underwent AHCT during the first study period and received antibacterial
      prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0
      14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4
      16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0
      12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode
      of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7,
      respectively. Patients with ciprofloxacin prophylaxis had higher rates of
      ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference
      44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis
      significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p <
      0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02). CONCLUSION:
      According to our single-centre experience, patients with MM and lymphoma
      undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin.

PMID- 29208562
TI  - Microbiologic factors affecting Clostridium difficile recurrence.
AB  - BACKGROUND: Recurrent Clostridium difficile infection (rCDI) places a huge
      economic and practical burden on healthcare facilities. Furthermore, rCDI may
      affect quality of life, leaving patients in an rCDI cycle and dependant on
      antibiotic therapy. AIMS: To discuss the importance of microbiologic factors in
      the development of rCDI. SOURCES: Literature was drawn from a search of PubMed
      from 2000 onwards with the search term 'recurrent Clostridium difficile
      infection' and further references cited within these articles. CONTENT: Meta
      analyses and systematic reviews have shown that CDI and rCDI risk factors are
      similar. Development of rCDI is attendant on many factors, including immune
      status or function, comorbidities and concomitant treatments. Studies suggest
      that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum
      gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole)
      are in development for CDI treatment, while microbiota therapeutics (faecal
      microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are
      increasingly being explored. rCDI can only occur when viable C. difficile spores
      are present, either within the gut lumen after infection or when reacquired from
      the environment. C. difficile spore germination can be influenced by gut
      environmental factors resulting from dysbiosis, and spore outgrowth may be
      affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin,
      oritavancin). IMPLICATIONS: rCDI is a significant challenge for healthcare
      professionals, requiring a multifaceted approach; optimized infection control to
      minimize reinfection; C. difficile-targeted antibiotics to minimize dysbiosis;
      and gut microflora restoration to promote colonization resistance. These elements
      should be informed by our understanding of the microbiologic factors involved in
      both C. difficile itself and the gut microbiome.

PMID- 29208563
TI  - Malignant perivascular epithelioid cell tumor of the oropharynx with strong TFE3
      expression mimicking alveolar soft part sarcoma: a case report and review of the
      literature.
AB  - Perivascular epithelioid cell tumors (PEComas) in the head and neck region are
      rare, with 26 cases described in literature. These distinct mesenchymal tumors
      normally express both myoid and melanocytic markers. We here report an
      interesting and challenging case of malignant PEComa that showed transcription
      factor E3 (TFE3) protein expression and rearrangement, paucity of muscle and
      melanocytic marker expression, and morphologically mimicked alveolar soft part
      sarcoma. Awareness of this morphologic pitfall and recognition of TFE3 gene
      rearranged PEComa, as a distinct subtype of PEComa, is essential to avoid
      misdiagnosis.

PMID- 29208564
TI  - Nectin-4 promotes gastric cancer progression via the PI3K/AKT signaling pathway.
AB  - Nectin-4, a member of the Nectin family that includes 4 Ca+-independent
      immunoglobulin-like cell adhesion molecules, plays a carcinogenic role in
      multiple cancers. However, Nectin-4 expression and its biological role in gastric
      cancer (GC) remain largely unknown. In this study, quantitative real-time
      polymerase chain reaction, Western blotting, and immunohistochemistry were used
      to evaluate the expression patterns of Nectin-4 in GC specimens and cell lines.
      We observed that high expression of Nectin-4 in GC patients was associated with
      TNM stage and lymph node metastasis status, and poor prognosis. In addition, cell
      proliferation and cell migration assays in vitro and tumorigenicity in vivo were
      performed to observe the effects of up-regulation and down-regulation of Nectin-4
      expression on GC cell phenotypes. In further studies, the PI3K/AKT signaling
      pathway was revealed to be involved in Nectin-4-mediated GC progression. These
      results demonstrated that Nectin-4 had a promoter effect on human GC cell growth
      and motility, indicating that Nectin-4 may serve as an effective therapeutic
      target in GC.

PMID- 29208565
TI  - Mismatch repair-deficient colorectal cancer: a model of immunogenic and immune
      cell-rich tumor despite nonsignificant programmed cell death ligand-1 expression
      in tumor cells.
AB  - Mismatch repair-deficient (dMMR) colorectal cancers (CRCs) are good responders to
      anti-programmed cell death ligand-1 (PD-L1) immunotherapy, but the value of PD-L1
      testing remains unclear. We studied PD-L1 expression and the tumor immune
      microenvironment in dMMR CRC as a model of good responders to immunotherapy. We
      examined 35 dMMR and 34 mismatch repair-proficient (pMMR) CRCs using immune cell
      markers (CD3, CD4, CD8, CD20, CD68, and FOXP3) as well as programmed cell death
      receptor-1 (PD-1) and PD-L1 immunohistochemistry staining in whole tumor
      specimens and tissue microarray slides to compare 4 PD-L1 immunohistochemistry
      clones (SP142, E1L3N, 22C3, and 28.8). We observed no significant difference in
      PD-L1 expression between dMMR and pMMR CRCs. Only 2 dMMR tumors had membranous PD
      L1 staining. Expression of PD-L1 was greater in stromal immune cells of dMMR CRC,
      which also contained more numerous intraepithelial (CD3+, CD8+, FOXP3+, and PD
      1+) and stromal (CD8+, PD-1+) lymphocytes than did pMMR tumors. Immune cell
      quantification discriminated better between dMMR and pMMR tumors than did PD-L1
      expression. Tumor heterogeneity and variations in PD-L1 expression were noted
      with different antibodies, especially for PD-L1+ immune cells, which were more
      numerous at the invasion margin. Given the poor correlation with mismatch repair
      status and technical limitations, the value of PD-L1 testing to accompany the
      development of anti-PD-1/PD-L1 immunotherapy remains unclear. Further clinical
      trials are required to determine which parameters are valuable predictive
      biomarkers of the response to immunotherapy among mismatch repair status, PD-L1
      expression, and immune cell quantification in CRC.

PMID- 29208566
TI  - MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF
      kappaB signaling pathway.
AB  - Osteoarthritis (OA) is the most common joint disease, characterized by articular
      cartilage degradation and changes in all other joint tissues. MicroRNAs (miRNAs)
      play an important role in mediating the main risk factors for OA. This study
      aimed to investigate the effect of miR-26a/26b on the proliferation and apoptosis
      of human chondrocytes by targeting fucosyltransferase 4 (FUT4) through NF-kappaB
      signaling pathway. We revealed the differential expression profiles of FUT4 and
      miR-26a/26b in the articular cartilage tissues of OA patients and normal people.
      The ability of miR-26a/26b to specifically interact with the 3'UTR of FUT4 was
      demonstrated via a luciferase reporter assay in chondrocytes. Further results
      showed altered levels of miR-26a/26b and FUT4 could regulate the process of IL
      1beta-induced extracellular matrix degradation in chondrocytes. Forced miR
      26a/26b expression was able to affect chondrocytes proliferation and apoptosis,
      while altered expression of FUT4 in chondrocytes modulated progression upon
      transfection with miR-26a/26b mimic or inhibitor. In OA mice, the overexpression
      of miR-26a/26b by intra-articular injection significantly attenuated OA
      progression. In addition, regulating FUT4 expression markedly modulated the
      activity of NF-kappaB signaling pathway, and this effect could be reversed by miR
      26a/26b. In short, miR-26a/-26b/FUT4/NF-kappaB axis may serve as a predictive
      biomarker and a potential therapeutic target in OA treatment.

PMID- 29208567
TI  - Phosphorylation of threonine residues on Shc promotes ligand binding and mediates
      crosstalk between MAPK and Akt pathways in breast cancer cells.
AB  - Scaffold proteins play important roles in regulating signalling network fidelity,
      the absence of which is often the basis for diseases such as cancer. In the
      present work, we show that the prototypical scaffold protein Shc is
      phosphorylated by the extracellular signal-regulated kinase, Erk. In addition,
      Shc threonine phosphorylation is specifically up-regulated in two selected triple
      negative breast cancer (TNBC) cell lines. To explore how Erk-mediated threonine
      phosphorylation on Shc might play a role in the dysregulation of signalling
      events, we investigated how Shc affects pathways downstream of EGF receptor.
      Using an in vitro model and biophysical analysis, we show that Shc threonine
      phosphorylation is responsible for elevated Akt and Erk signalling, potentially
      through the recruitment of the 14-3-3 zeta and Pin-1 proteins.

PMID- 29208568
TI  - Overexpression of ELF3 facilitates cell growth and metastasis through PI3K/Akt
      and ERK signaling pathways in non-small cell lung cancer.
AB  - ELF3 is one of the member of transcription factors from E-twenty-six family, its
      role varies in different types of cancer. However, the role and specific
      mechanisms of ELF3 in the development of non-small cell lung cancer (NSCLC) still
      remains largely unknown. In our study, ELF3 was observed to be upregulated in
      NSCLC tissues compared to the corresponding normal lung tissue at mRNA and
      protein levels, and its expression level was correlated with the overall survival
      of patients with NSCLC. Silencing of the ELF3 gene in NSCLC cells inhibited the
      proliferation and metastasis significantly in vitro and in vivo. Conversely,
      overexpression of ELF3 in NSCLC cells promoted cancer growth and metastasis in
      vitro. Mechanistically, ELF3 activated PI3K/AKT and ERK signaling pathways and
      its downstream effectors, thus regulating the cell cycle and epithelial
      mesenchymal transition (EMT). Furthermore, the promotive effects of ELF3 on
      cellular proliferation and metastasis could be rescued by Ly294002 (inhibitor of
      PI3K) and U0126 (inhibitor of MEK1/2). The results show that ELF3 promotes cell
      growth and metastasis by regulating PI3K/Akt and ERK pathways in NSCLC and that
      it may be a promising new target for the treatment of NSCLC patients.

PMID- 29208570
TI  - Modelling and interpretation of magnetization transfer imaging in the brain.
AB  - Magnetization transfer contrast has yielded insight into brain tissue
      microstructure changes across the lifespan and in a range of disorders. This
      progress has been aided by the development of quantitative magnetization transfer
      imaging techniques able to extract intrinsic properties of the tissue that are
      independent of the specifics of the data acquisition. While the tissue properties
      extracted by these techniques do not map directly onto specific cellular
      structures or pathological processes, a growing body of work from animal models
      and histopathological correlations aids the in vivo interpretation of
      magnetization transfer properties of tissue. This review examines the biophysical
      models that have been developed to describe magnetization transfer contrast in
      tissue as well as the experimental evidence for the biological interpretation of
      magnetization transfer data in health and disease.

PMID- 29208569
TI  - A digital 3D atlas of the marmoset brain based on multi-modal MRI.
AB  - The common marmoset (Callithrix jacchus) is a New-World monkey of growing
      interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool
      to unveil the anatomical and functional organization of the marmoset brain. To
      facilitate identification of regions of interest, it is desirable to register MR
      images to an atlas of the brain. However, currently available atlases of the
      marmoset brain are mainly based on 2D histological data, which are difficult to
      apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on
      high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1
      like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi
      modal MRI images, we manually delineated 54 cortical areas and 16 subcortical
      regions on one hemisphere of the brain (the core version). The 54 cortical areas
      were merged into 13 larger cortical regions according to their locations to yield
      a coarse version of the atlas, and also parcellated into 106 sub-regions using a
      connectivity-based parcellation method to produce a refined atlas. Finally, we
      compared the new atlas set with existing histology atlases and demonstrated its
      applications in connectome studies, and in resting state and stimulus-based fMRI.
      The atlas set has been integrated into the widely-distributed neuroimaging data
      analysis software AFNI and SUMA, providing a readily usable multi-modal template
      space with multi-level anatomical labels (including labels from the Paxinos
      atlas) that can facilitate various neuroimaging studies of marmosets.

PMID- 29208571
TI  - Using multi-echo simultaneous multi-slice (SMS) EPI to improve functional MRI of
      the subcortical nuclei of the basal ganglia at ultra-high field (7T).
AB  - The nuclei of the basal ganglia pose a special problem for functional MRI,
      especially at ultra-high field, because T2* variations between different regions
      result in suboptimal BOLD sensitivity when using gradient-echo echo-planar
      imaging (EPI). Specifically, the iron-rich lentiform nucleus of the basal
      ganglia, including the putamen and globus pallidus, suffers from substantial
      signal loss when imaging is performed using conventional single-echo EPI with
      echo times optimized for the cortex. Multi-echo EPI acquires several echoes at
      different echo times for every imaging slice, allowing images to be reconstructed
      with a weighting of echo times that is optimized individually for each voxel
      according to the underlying tissue or T2* properties. Here we show that multi
      echo simultaneous multi-slice (SMS) EPI can improve functional activation of iron
      rich subcortical regions while maintaining sensitivity within cortical areas.
      Functional imaging during a motor task known to elicit strong activations in the
      cortex and the subcortex (basal ganglia) was performed to compare the performance
      of multi-echo SMS EPI to single-echo SMS EPI. Notably within both the caudate
      nucleus and putamen of the basal ganglia, multi-echo SMS EPI yielded higher tSNR
      (an average 84% increase) and CNR (an average 58% increase), an approximate 3
      fold increase in supra-threshold voxels, and higher t-values (an average 39%
      increase). The degree of improvement in the group level t-statistics was
      negatively correlated to the underlying T2* of the voxels, such that the shorter
      the T2*, as in the iron-rich nuclei of the basal ganglia, the higher the
      improvement of t-values in the activated region.

PMID- 29208573
TI  - Swimming against the tide: insights from the ORBITA trial.

PMID- 29208572
TI  - Experimental studies of g-ratio MRI in ex vivo mouse brain.
AB  - This study aimed to experimentally evaluate a previously proposed MRI method for
      mapping axonal g-ratio (ratio of axon diameters, measured to the inner and outer
      boundary of myelin). MRI and electron microscopy were used to study excised and
      fixed brains of control mice and three mouse models of abnormal white matter. The
      results showed that g-ratio measured with MRI correlated with histological
      measures of myelinated axon g-ratio, but with a bias that is likely due to the
      presence of non-myelinated axons. The results also pointed to cases where the MRI
      g-ratio model simplifies to be primarily a function of total myelin content.

PMID- 29208574
TI  - Experimental validation of TMVR technologies: a bumpy road with the risk of
      getting lost in translation.

PMID- 29208575
TI  - Grow your own valve.

PMID- 29208576
TI  - Editorial on "Characteristics of extension and de novo recurrent spontaneous
      coronary artery dissection".

PMID- 29208577
TI  - Lost in translational filters between peers.

PMID- 29208578
TI  - Endeavours to define optimal antithrombotic therapy after percutaneous coronary
      intervention.

PMID- 29208579
TI  - cFFR as an alternative to FFR: please do not contrast simplicity!

PMID- 29208580
TI  - Wire externalisation techniques for retrograde percutaneous coronary
      interventions of chronic total occlusions.

PMID- 29208581
TI  - How should I treat a left persistent superior vena cava with unroofed coronary
      sinus associated with severe stenosis and regurgitation of aortic homograft
      placed in the tricuspid position?

PMID- 29208582
TI  - Bacterial, fungal, parasitological and pathological analyses of abortions in
      small ruminants from 2012-2016.
AB  - INTRODUCTION: Abortion in small ruminants presents a clinical and economic
      problem with legal implications regarding animal health and zoonotic risk by some
      of the abortive pathogens. Several bacteria, fungi and parasites can cause
      abortion, but cost-orientated routine diagnostics only cover the most relevant
      epizootic agents. To cover a broad-range of common as well as underdiagnosed
      abortifacients, we studied 41 ovine and 36 caprine abortions by Stamp's
      modification of the Ziehl-Neelsen stain, culture for classical and opportunistic
      abortive agents, real-time PCR for C. burnetii, C. abortus, pathogenic Leptospira
      spp., Toxoplasma gondii and Neospora caninum. When the dam's serum was available
      detection of antibodies against B. melitensis, C. burnetii, C. abortus and
      Leptospira spp. was performed. In 37 cases sufficient placental tissue was
      available for pathological and histopathological examination. From the 77 cases
      11 (14.3%) were positive by staining whereas real-time PCR detected C. burnetii
      and C. abortus in 49.3% and 32.5% of the cases. Antibodies against C. abortus and
      Leptospira spp. (33.3 and 26.7%) were detected. In 23.4% a bacterial culturable
      pathogen was isolated. Fungal abortion was confirmed in 1.3% of cases. A single
      abortive agent was identified in 44.2% of the cases and in 31.2% multiple
      possible abortifacients were present. Our study shows that the highest
      clarification rate can only be achieved by a combination of methods and evidences
      the role that multi-infections play as cause of abortion.

PMID- 29208584
TI  - Outbreak of Highly Pathogenic Avian Influenza H5N8 in November 2016 in Wild Birds
      in Switzerland.

PMID- 29208583
TI  - Challenging anaesthetic management of captive reindeer (Rangifer tarandus):
      Report of 4 cases.
AB  - INTRODUCTION: Four captive reindeer underwent anaesthesia to allow dehorning or
      drainage of lymph nodes abscessation. Premedication was based on xylazine (dose
      range: 0.075- 0.5 mg/kg, IM or IV), with or without ketamine (dose range: 1-2
      mg/kg, IM or IV), all of which failed to produce effective sedation without side
      effects. During anaesthesia, 2 reindeer experienced severe hypoxaemia and
      hypoventilation. Recovery was smooth in 3 out 4 animals, but delayed in one
      reindeer sedated with 0.5 mg/kg of xylazine IV; this patient required repeated
      atipamezole administrations (0.01 mg/kg IM given 3 times) to regain normal
      locomotion. Anaesthesia of reindeer is challenging and useful dose ranges for
      safe and effective anaesthesia are mostly unknown.

PMID- 29208585
TI  - ?

PMID- 29208586
TI  - Mastitis associated with Mycobacterium smegmatis complex members in a Swiss dairy
      cattle herd: compost bedding material as a possible risk factor.

PMID- 29208587
TI  - HIV Surveillance Among Pregnant Women Attending Antenatal Clinics: Evolution and
      Current Direction.
AB  - Since the late 1980s, human immunodeficiency virus (HIV) sentinel
      serosurveillance among pregnant women attending select antenatal clinics (ANCs)
      based on unlinked anonymous testing (UAT) has provided invaluable information for
      tracking HIV prevalence and trends and informing global and national HIV models
      in most countries with generalized HIV epidemics. However, increased coverage of
      HIV testing, prevention of mother-to-child transmission (PMTCT), and
      antiretroviral therapy has heightened ethical concerns about UAT. PMTCT programs
      now routinely collect demographic and HIV testing information from the same
      pregnant women as serosurveillance and therefore present an alternative to UAT
      based ANC serosurveillance. This paper reports on the evolution and current
      direction of the global approach to HIV surveillance among pregnant women
      attending ANCs, including the transition away from traditional UAT-based
      serosurveillance and toward new guidance from the World Health Organization and
      the Joint United Nations Programme on HIV/AIDS on the implementation of
      surveillance among pregnant women attending ANCs based on routine PMTCT program
      data.

PMID- 29208588
TI  - App-Supported Promotion of Child Growth and Development by Community Health
      Workers in Kenya: Feasibility and Acceptability Study.
AB  - BACKGROUND: Early childhood is a critical phase of development. In low resource
      settings, monitoring this stage of development and providing appropriate and
      timely feedback is a challenge. Community-based service providers play a key role
      in promoting early childhood development in areas where government services are
      weak. These community-based service providers are also tasked with the collection
      of monitoring and evaluation data for donors and local government. Usually,
      collection of these data aims to provide accountability, learning, and correction
      leading to improvement. However, such data is rarely used beyond the
      accountability stage. OBJECTIVE: The purpose of this study was to test the
      feasibility and acceptability of the Information for Action (IFA) mobile phone
      app. The IFA app was designed for use by community health volunteers (CHVs), and
      repackages routinely collected data about children into useful, offline decision
      support for caregivers and program managers. METHODS: The IFA app was tested with
      a convenience sample of 10 CHVs in West Katweng'a, a sublocation of Rarieda
      subcounty in western Kenya. CHVs used the IFA app for 5 months as part of their
      regular home visits to households containing children aged 0 to 5 years, after
      which a qualitative assessment of the app was conducted. A total of 16 caregivers
      who received services from the CHVs were randomly selected to participate in 1 of
      2 focus group discussions about their experience. RESULTS: The app was reported
      to help facilitate interactive dialog between CHVs and caregivers, leading to
      improved quality of home visits. Caregivers described the app as shifting the
      relationship from feeling harassed by CHVs to experiencing genuine interest from
      CHVs. CHVs reported feasibility challenges primarily related to infrastructure.
      The limited battery life of mobile phones combined with the lack of readily
      available electricity made it difficult to keep the phones charged. CHVs reported
      initial anxiety as first-time mobile phones users, including concerns about using
      the IFA app. With time, increased levels of confidence were seen. CONCLUSIONS:
      Acceptability was high with both CHVs and caregivers, who reported an improvement
      in their client-provider relationship. A number of feasibility challenges were
      experienced.

PMID- 29208589
TI  - Development of an Index of Engagement in HIV Care: An Adapted Internet-Based
      Delphi Process.
AB  - BACKGROUND: Improving engagement in medical care among persons living with human
      immunodeficiency virus (HIV) is critical to optimizing clinical outcomes and
      reducing onward transmission of HIV. However, a clear conceptualization of what
      it means to be engaged in HIV care is lacking, and thus efforts to measure and
      enhance engagement in care are limited. OBJECTIVE: This paper describes the use
      of a modified online Delphi process of consensus building to solicit input from a
      range of HIV and non-HIV researchers and providers, and to integrate that input
      with focus group data conducted with HIV-infected patients. The overarching goal
      was to generate items for a patient-centered measure of engagement in HIV care
      for use in future research and clinical practice. METHODS: We recruited 66 expert
      panelists from around the United States. Starting with six open-ended questions,
      we used four rounds of online Delphi data collection in tandem with 12 in-person
      focus groups with patients and cognitive interviews with 25 patients. RESULTS: We
      recruited 66 expert panelists from around the United States and 64 (97%) were
      retained for four rounds of data collection. Starting with six open-ended
      questions, we used four rounds of online Delphi data collection in tandem with 12
      in-person focus groups with patients and cognitive interviews with 25 patients.
      The process resulted in an expansion to 120 topics that were subsequently reduced
      to 13 candidate items for the planned assessment measure. CONCLUSIONS: The
      process was an efficient method of soliciting input from geographically separated
      and busy experts across a range of disciplines and professional roles with the
      aim of arriving at a coherent definition of engagement in HIV care and a
      manageable set of survey items to assess it. Next steps are to validate the
      utility of the new measure in predicting retention in care, adherence to
      treatment, and clinical outcomes among patients living with HIV.

PMID- 29208591
TI  - The Second-Look Procedure for Transoral Videolaryngoscopic Surgery for T1 and T2
      Laryngeal, Oropharyngeal, and Hypopharyngeal Cancer Patients: Protocol for a
      Nonrandomized Clinical Trial.
AB  - BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) has been widely applied
      for early T stage head and neck cancer. The resection is performed with a minimum
      safety margin for function preservation under a limited surgical field of view,
      making it difficult to be certain of complete resection. OBJECTIVE: Our aim is
      the evaluation of the completeness of resection by initial TOVS resection, and
      the possibility of primary control by TOVS alone, allowing for repeat procedures
      for function preserving treatment in early T stage laryngeal, oropharyngeal, and
      hypopharyngeal cancer patients. METHODS: Patients are treated by TOVS for the
      primary site with or without neck dissection. Patients are divided in two groups
      based on the results of the pathological evaluation of the surgical specimen; the
      control group in which the resection is considered to be complete, and the
      intervention (second-look procedure) group in which incomplete tumor resection is
      suspected. The predictive factors for the possibility of complete resection by
      TOVS will then be analyzed. RESULTS: Patient enrollment started on January 1,
      2014, and closed on March 31, 2016, with 54 patients. The control group consists
      of 27 patients, the intervention group is 21 patients, and 6 patients were
      excluded. There were no clinical differences between the control and intervention
      groups. The observation period will end on December 31, 2018. CONCLUSIONS: TOVS
      has potential for both definitive resection and function preservation with
      minimal invasiveness. Identifying the limitations of TOVS is beneficial to ensure
      accurate treatment selection in early T stage head and neck cancer patients.
      TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000012485;
      https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000014472
      (Archived by WebCite at http://www.webcitation.org/6v1b741Iw).

PMID- 29208592
TI  - Missing several GP appointments could be warning sign, say researchers.

PMID- 29208590
TI  - The National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study
      Cohort: Rationale, Methods, and Baseline Characteristics.
AB  - BACKGROUND: Although bariatric procedures are commonly performed in clinical
      practice, long-term data on the comparative effectiveness and safety of different
      procedures on sustained weight loss, comorbidities, and adverse effects are
      limited, especially in important patient subgroups (eg, individuals with
      diabetes, older patients, adolescents, and minority patients). OBJECTIVE: The
      objective of this study was to create a population-based cohort of patients who
      underwent 3 commonly performed bariatric procedures-adjustable gastric band
      (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine
      the long-term comparative effectiveness and safety of these procedures in both
      adults and adolescents. METHODS: We identified adults (20 to 79 years old) and
      adolescents (12 to 19 years old) who underwent a primary (first observed) AGB,
      RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42
      health systems participating in the Clinical Data Research Networks within the
      National Patient-Centered Clinical Research Network (PCORnet). We extracted
      information on patient demographics, encounters with healthcare providers,
      diagnoses recorded and procedures performed during these encounters, vital signs,
      and laboratory test results from patients' electronic health records (EHRs). The
      outcomes of interest included weight change, incidence of major surgery-related
      adverse events, and diabetes remission and relapse, collected for up to 10 years
      after the initial bariatric procedure. RESULTS: A total of 65,093 adults and 777
      adolescents met the eligibility criteria of the study. The adult subcohort had a
      mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among
      adult patients with non-missing race or ethnicity information, 72.08%
      (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58%
      (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded
      in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric
      procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%,
      29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent
      subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients
      with known race or ethnicity information, 67.3% (473/703) were White, 22.6%
      (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest
      recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the
      adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%,
      239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was
      available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56%
      (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up,
      respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349),
      and 38.8% (47/121) in the adolescent subcohort. CONCLUSIONS: Our study cohort is
      one of the largest cohorts of patients with bariatric procedures in the United
      States. Patients are geographically and demographically diverse, which improves
      the generalizability of the research findings and allows examination of treatment
      effect heterogeneity. Ongoing and planned investigations will provide real-world
      evidence on the long-term benefits and risks of these most commonly used
      bariatric procedures in current clinical practice.

PMID- 29208593
TI  - Adenovirus infection: beware of plasma procalcitonin levels in children.

PMID- 29208595
TI  - GP who falsified prescriptions to treat his depression is suspended for 12
      months.

PMID- 29208594
TI  - Sixty seconds on . . . flu vaccine for health staff.

PMID- 29208596
TI  - Urinary 8-Hydroxy-2'-Deoxyguanosine as a Myocardial Oxidative Stress Marker Is
      Associated With Ventricular Tachycardia in Patients With Active Cardiac
      Sarcoidosis.
AB  - BACKGROUND: Recently, we reported that urinary 8-hydroxy-2'-deoxyguanosine (U-8
      OHdG), an oxidative stress marker, reflected inflammatory activity in cardiac
      sarcoidosis (CS). Here, we investigated whether U-8-OHdG levels were associated
      with ventricular tachycardia (VT) in patients with CS. METHODS AND RESULTS: This
      prospective cohort study enrolled 62 consecutive patients with CS, of whom 36
      were diagnosed as having active CS based on abnormal 18F-flurodeoxyglucose
      accumulation in the heart on positron-emission tomography/computed tomography.
      The 36 patients with active CS were subdivided as having CS with sustained VT (CS
      VT group; n=18) or CS without sustained VT (CS-nVT group; n=18). Twenty-seven
      patients diagnosed with idiopathic dilated cardiomyopathy served as heart failure
      controls. U-8-OHdG, brain natriuretic peptide, cardiac function indices, and
      immunohistological data from subendomyocardial biopsy samples were compared
      across groups. Immunohistochemical examination of ventricle biopsy samples
      revealed that the anti-8-OHdG antibody-positive area of cardiac tissue was
      significantly greater in CS-VT than in CS-nVT or dilated cardiomyopathy and
      significantly correlated with U-8-OHdG levels (n=58; R=0.61; P<0.00001), which
      were significantly higher in CS-VT than in CS-nVT (24.6+/-7.1 versus 15.2+/-3.8
      ng/mg.Cr; P<0.0001). Other baseline characteristics did not differ between the
      groups. Multivariate analysis indicated that U-8-OHdG was an independent
      determinant factor for VT. Receiver operating characteristic curve analysis to
      identify patients with VT resulted in a U-8-OHdG cutoff value of 17.5 ng/mg.Cr
      (sensitivity, 89%; specificity, 83%; area under the curve, 0.90). CONCLUSIONS: U
      8-OHdG levels are associated with VT in patients with active CS diagnosed by 18F
      flurodeoxyglucose positron-emission tomography, providing additive and relevant
      information about the arrhythmia substrate.

PMID- 29208597
TI  - Unraveling Inflammation and Oxidative Stress in Cardiac Sarcoidosis.

PMID- 29208598
TI  - Myosin IIa is critical for cAMP-mediated endothelial secretion of von Willebrand
      factor.
AB  - Nonmuscle myosin II has been implicated in regulation of von Willebrand factor
      (VWF) release from endothelial Weibel-Palade bodies (WPBs), but the specific role
      of myosin IIa isoform is poorly defined. Here, we report that myosin IIa is
      expressed both in primary human endothelial cells and intact mouse vessels,
      essential for cyclic adenosine monophosphate (cAMP)-mediated endothelial VWF
      secretion. Downregulation of myosin IIa by shRNAs significantly suppressed both
      forskolin- and epinephrine-induced VWF secretion. Endothelium-specific myosin IIa
      knockout mice exhibited impaired epinephrine-stimulated VWF release, prolonged
      bleeding time, and thrombosis. Further study showed that in resting cells, myosin
      IIa deficiency disrupted the peripheral localization of Rab27-positive WPBs along
      stress fibers; on stimulation by cAMP agonists, myosin IIa in synergy with zyxin
      promotes the formation of a functional actin framework, which is derived from
      preexisting cortical actin filaments, around WPBs, facilitating fusion and
      subsequent exocytosis. In summary, our findings not only identify new functions
      of myosin IIa in regulation of WPB positioning and the interaction between
      preexisting cortical actin filaments and exocytosing vesicles before fusion but
      also reveal myosin IIa as a physiological regulator of endothelial VWF secretion
      in stress-induced hemostasis and thrombosis.

PMID- 29208599
TI  - Prognostic miRNA classifier in early-stage mycosis fungoides: development and
      validation in a Danish nationwide study.
AB  - Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma.
      The disease often takes an indolent course, but in approximately one-third of the
      patients, the disease progresses to an aggressive malignancy with a poor
      prognosis. At the time of diagnosis, it is impossible to predict which patients
      develop severe disease and are in need of aggressive treatment. Accordingly, we
      investigated the prognostic potential of microRNAs (miRNAs) at the time of
      diagnosis in MF. Using a quantitative reverse transcription polymerase chain
      reaction platform, we analyzed miRNA expression in diagnostic skin biopsies from
      154 Danish patients with early-stage MF. The patients were subdivided into a
      discovery cohort (n = 82) and an independent validation cohort (n = 72). The
      miRNA classifier was built using a LASSO (least absolute shrinkage and selection
      operator) Cox regression to predict progression-free survival (PFS). We developed
      a 3-miRNA classifier, based on miR-106b-5p, miR-148a-3p, and miR-338-3p, which
      successfully separated patients into high-risk and low-risk groups of disease
      progression. PFS was significantly different between these groups in both the
      discovery cohort and the validation cohort. The classifier was stronger than
      existing clinical prognostic factors and remained a strong independent prognostic
      tool after stratification and adjustment for these factors. Importantly, patients
      in the high-risk group had a significantly reduced overall survival. The 3-miRNA
      classifier is an effective tool to predict disease progression of early-stage MF
      at the time of diagnosis. The classifier adds significant prognostic value to
      existing clinical prognostic factors and may facilitate more individualized
      treatment of these patients.

PMID- 29208601
TI  - Traffic pollution is linked to poor pregnancy outcomes.

PMID- 29208603
TI  - Will STPs lead to further cuts to health and social care?

PMID- 29208604
TI  - JCAR015 in ALL: A Root-Cause Investigation.
AB  - After conducting an internal probe of the five deaths that halted JCAR015's
      development for acute lymphoblastic leukemia, Juno Therapeutics has concluded
      that multiple factors were at play. A surge in inflammatory cytokine levels from
      rapid, early T-cell proliferation may have provoked the blood-brain barrier
      disruption seen in these patients, inducing fatal cerebral edema.

PMID- 29208605
TI  - Progress on malaria stalls amid decline in funding.

PMID- 29208602
TI  - Impact of London's road traffic air and noise pollution on birth weight:
      retrospective population based cohort study.
AB  - Objective To investigate the relation between exposure to both air and noise
      pollution from road traffic and birth weight outcomes.Design Retrospective
      population based cohort study.Setting Greater London and surrounding counties up
      to the M25 motorway (2317 km2), UK, from 2006 to 2010.Participants 540 365
      singleton term live births.Main outcome measures Term low birth weight (LBW),
      small for gestational age (SGA) at term, and term birth weight.Results Average
      air pollutant exposures across pregnancy were 41 MUg/m3 nitrogen dioxide (NO2),
      73 MUg/m3 nitrogen oxides (NOx), 14 MUg/m3 particulate matter with aerodynamic
      diameter <2.5 MUm (PM2.5), 23 MUg/m3 particulate matter with aerodynamic diameter
      <10 MUm (PM10), and 32 MUg/m3 ozone (O3). Average daytime (LAeq,16hr) and night
      time (Lnight) road traffic A-weighted noise levels were 58 dB and 53 dB
      respectively. Interquartile range increases in NO2, NOx, PM2.5, PM10, and source
      specific PM2.5 from traffic exhaust (PM2.5 traffic exhaust) and traffic non
      exhaust (brake or tyre wear and resuspension) (PM2.5 traffic non-exhaust) were
      associated with 2% to 6% increased odds of term LBW, and 1% to 3% increased odds
      of term SGA. Air pollutant associations were robust to adjustment for road
      traffic noise. Trends of decreasing birth weight across increasing road traffic
      noise categories were observed, but were strongly attenuated when adjusted for
      primary traffic related air pollutants. Only PM2.5 traffic exhaust and PM2.5 were
      consistently associated with increased risk of term LBW after adjustment for each
      of the other air pollutants. It was estimated that 3% of term LBW cases in London
      are directly attributable to residential exposure to PM2.5>13.8 MUg/m3during
      pregnancy.Conclusions The findings suggest that air pollution from road traffic
      in London is adversely affecting fetal growth. The results suggest little
      evidence for an independent exposure-response effect of traffic related noise on
      birth weight outcomes.

PMID- 29208606
TI  - Emerging Role of CRISPR/Cas9 Technology for MicroRNAs Editing in Cancer Research.
AB  - MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the
      regulation of important tasks in different critical processes of cancer
      pathogenesis. Because there are different miRNAs implicated in all the stages of
      cancer, for example, functioning as oncogenes, this makes these small molecules
      suitable targets for cancer diagnosis and therapy. RNA-mediated interference has
      been one major approach for sequence-specific regulation of gene expression in
      eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short
      palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an
      adaptive immune response to invading genetic material, has been explored as a
      sequence-specific molecular tool for editing genomic sequences for basic research
      in life sciences and for therapeutic purposes. There is growing evidence that
      small noncoding RNAs, including miRNAs, can be targeted by the CRISPR/Cas9 system
      despite their lacking an open reading frame to evaluate functional loss. Thus,
      CRISPR/Cas9 technology represents a novel gene-editing strategy with compelling
      robustness, specificity, and stability for the modification of miRNA expression.
      Here, I summarize key features of current knowledge of genomic editing by
      CRISPR/Cas9 technology as a feasible strategy for globally interrogating miRNA
      gene function and miRNA-based therapeutic intervention. Alternative emerging
      strategies for nonviral delivery of CRISPR/Cas9 core components into human cells
      in a clinical context are also analyzed critically. Cancer Res; 77(24); 6812-7.
      (c)2017 AACR.

PMID- 29208607
TI  - Four week target for children to access mental health services proposed.

PMID- 29208608
TI  - Corticosteroids for sore throat: a clinical practice guideline.

PMID- 29208609
TI  - NHS England and government are on collision course over funding.

PMID- 29208610
TI  - Welsh opt-out law fails to increase organ donations.

PMID- 29208611
TI  - Perturbations of NAD+ salvage systems impact mitochondrial function and energy
      homeostasis in mouse myoblasts and intact skeletal muscle.
AB  - Nicotinamide adenine dinucleotide (NAD+) can be synthesized by nicotinamide
      phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT in
      maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in
      skeletal muscle cells. We generated stable Nampt knockdown (sh Nampt KD) C2C12
      cells using a shRNA lentiviral approach. Moreover, we applied gene
      electrotransfer to express Cre recombinase in tibialis anterior muscle of floxed
      Nampt mice. In sh Nampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by
      70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%.
      Moreover, anaerobic glycolytic flux increased by 55%, and 2-deoxyglucose uptake
      increased by 25% in sh Nampt KD cells. Treatment with the NAD+ precursor
      nicotinamide riboside restored NAD+ levels in sh Nampt cells and increased
      maximal respiratory capacity by 18% and 32% in control and sh Nampt KD cells,
      respectively. Expression of Cre recombinase in muscle of floxed Nampt mice
      reduced NAMPT and NAD+ levels by 38% and 43%, respectively. Glucose uptake
      increased by 40%, and mitochondrial complex IV respiration was compromised by
      20%. Hypoxia-inducible factor (HIF)-1alpha-regulated genes and histone H3 lysine
      9 (H3K9) acetylation, a known sirtuin 6 (SIRT6) target, were increased in shNampt
      KD cells. Thus, we propose that the shift toward glycolytic metabolism observed,
      at least in part, is mediated by the SIRT6/HIF1alpha axis. Our findings suggest
      that NAMPT plays a key role for maintaining NAD+ levels in skeletal muscle and
      that NAMPT deficiency compromises oxidative phosphorylation capacity and alters
      energy homeostasis in this tissue.

PMID- 29208612
TI  - Increased body fat mass explains the positive association between circulating
      estradiol and insulin resistance in postmenopausal women.
AB  - The relationship between circulating estrogen levels and cardiometabolic risk
      factors such as insulin resistance is unclear in postmenopausal women. High
      estradiol (E2) levels have been reported to predict increased risk of type 2
      diabetes in this population. We aimed to examine associations among estrogen
      levels, adiposity measurements, and cardiometabolic risk variables including
      insulin resistance in postmenopausal women. One hundred-one healthy participants
      (mean +/- SD: age 57 +/- 4 yr, BMI 27.9 +/- 4.8 kg/m2) were included in the
      analysis. Fifteen plasma steroids or metabolites were measured by liquid
      chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a
      hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were
      determined with hydrostatic weighing and computed tomography, respectively. Blood
      lipids and circulating cytokines were also measured. Circulating E2 was
      positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001)
      except waist-to-hip ratio. E2 was positively correlated with VLDL-cholesterol,
      plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well
      as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL
      cholesterol, adiponectin, and insulin sensitivity ( r = -0.36 to -0.20, P <
      0.02). With adjustments for percent body fat, correlations between E2 and
      metabolic risk variables were no longer significant. Similar results were
      observed for circulating estrone (E1) and estrone-sulfate (E1-S) levels. In
      conclusion, circulating estrogen concentrations are proportional to adipose mass
      in postmenopausal women, although they remain in the low range. Insulin
      resistance as well as altered blood lipids and cytokines are observed when
      circulating estrogen levels are high within that range, but these differences are
      explained by concomitant variation in total adiposity.

PMID- 29208613
TI  - Do skeletal muscle-secreted factors influence the function of pancreatic beta
      cells?
AB  - Skeletal muscle is an endocrine organ that secretes a variety of compounds
      including proteins (myokines), metabolites, microRNAs (miRNAs), and exosomes,
      many of which are regulated by exercise and play important roles in endocrine
      signaling. Interorgan communication via muscle-secreted factors therefore
      provides a novel area for investigation and implicates the importance of skeletal
      muscle in the pathophysiology of metabolic diseases such as type 2 diabetes
      (T2D). Given that underlying molecular mechanisms of T2D are subject of ongoing
      research, in light of new evidence it is probable that interorgan cross-talk
      between skeletal muscle and pancreatic beta-cells plays an important part. To
      date, the number of studies published in this field provide the basis of this
      review. Specifically, we discuss current experimental evidence in support for a
      role of skeletal muscle to beta-cell cross-talk, paying particular attention to
      muscle-secreted factors including myokines, metabolites, miRNAs, and factors
      contained within exosomes that influence the function and/or the survival of beta
      cells in health and disease. In reviewing this evidence, we provide an update on
      the list of known muscle-secreted factors that have potential to influence the
      function and/or survival of beta-cells under normal and diabetic conditions. We
      also report limitations of current cross-talk methods and discuss future
      directions in this growing field.

PMID- 29208614
TI  - Association between hospitalisation for ambulatory care-sensitive conditions and
      primary health care physician specialisation: a cross-sectional ecological study
      in Curitiba (Brazil).
AB  - INTRODUCTION: Hospitalisation for ambulatory care-sensitive conditions (HACSCs)
      is frequently used as an indicator of the quality and effectiveness of primary
      healthcare (PHC) services around the world. The aim of the present study was to
      evaluate whether the PHC model (family health strategy (FHS) x conventional) and
      the availability of specialised PHC physicians is associated or not with total
      hospitalisation or HACSCs in the National Health System (SUS) of the municipality
      of Curitiba, Parana state (PR), Brazil. METHODOLOGY: This is a cross-sectional
      ecological study using multiple linear regression with socioeconomic and
      professional data from municipal health units (MHUs) between 1 April 2014 and 31
      March 2015. RESULTS: After adjustment for age and sex and control of
      socioeconomic variables, the FHS model was associated with six fewer HACSCs a
      year per 10 000 inhabitants in relation to the conventional model and the
      availability of one family physician at each FHS model MHU per 10 000 inhabitants
      was associated with 1.1 fewer HACSCs for heart failure a year per 10 000
      inhabitants. Basic specialists (clinicians, paediatricians and
      obstetrician/gynaecologists) and subspecialists showed no significant association
      with HACSC rates. CONCLUSION: These results obtained in a major Brazilian city
      reinforce the role of FHS as a priority PHC model in the country and indicate the
      potentially significant impact of specialising in family medicine on improving
      the health conditions of the population.

PMID- 29208615
TI  - Association between exercise and the risk of dementia: results from a nationwide
      longitudinal study in China.
AB  - OBJECTIVE: This study was conducted to examine the causal association between
      exercise and the risk of dementia among older Chinese adults. DESIGN:
      Longitudinal population-based study with a follow-up duration of 9 years.
      SETTING: Data for the Chinese Longitudinal Healthy Longevity Survey waves
      occurring from 2002 to 2011-2012 were extracted from the survey database.
      PARTICIPANTS: In total, 7501 dementia-free subjects who were older than 65 years
      were included at baseline. Dementia was defined as a self-reported or proxy
      reported physician's diagnosis of the disease. OUTCOME MEASURES AND METHODS:
      Regular exercise and potential confounding variables were obtained via a self
      report questionnaire. We generated longitudinal logistic regression models based
      on time-lagged generalised estimating equation to examine the causal association
      between exercise and dementia risk. RESULTS: Of the 7501 older Chinese people
      included in this study, 338 developed dementia during the 9-year follow-up period
      after excluding those who were lost to follow-up or deceased. People who
      regularly exercised had lower odds of developing dementia (OR=0.53, 95% CI 0.33
      to 0.85) than those who did not exercise regularly. CONCLUSION: Regular exercise
      was associated with decreased risk of dementia. Policy-makers should develop
      effective public health programmes and build exercise-friendly environments for
      the general public.

PMID- 29208616
TI  - Measuring clinical trial transparency: an empirical analysis of newly approved
      drugs and large pharmaceutical companies.
AB  - OBJECTIVES: To define a series of clinical trial transparency measures and apply
      them to large pharmaceutical and biotechnology companies and their 2014 FDA
      approved drugs. DESIGN: Cross-sectional descriptive analysis of all clinical
      trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug
      applications (NDAs) for novel drugs sponsored by large companies. DATA SOURCES:
      Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate
      and international registries; PubMed, Google Scholar, EMBASE, corporate press
      releases, Securities and Exchange Commission (SEC) filings and personal
      communications with drug manufacturers. OUTCOME MEASURES: Trial registration,
      results reporting, clinical study report (CSR) synopsis sharing, biomedical
      journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the
      drug level. RESULTS: The FDA approved 19 novel new drugs, sponsored by 11 large
      companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per
      drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71%
      (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were
      published and 96% (80%-100%) were publicly available in some form by 13 months
      after FDA approval. Disclosure rates were lower at FDA approval (65%) and
      improved significantly by 6 months post FDA approval. Per drug, a median of 100%
      (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs
      had publicly disclosed results for all trials in patients in our sample. One
      trial was uniquely registered in a corporate registry, and not
      ClinicalTrials.gov; 0 trials were uniquely registered in international
      registries. CONCLUSIONS: Among large pharmaceutical companies and new drugs,
      clinical trial transparency is high based on several standards, although
      opportunities for improvement remain. Transparency is markedly higher for trials
      in patients than among all trials supporting drug approval, including trials in
      healthy volunteers. Ongoing efforts to publicly track companies' transparency
      records and recognise exemplary companies may encourage further progress.

PMID- 29208618
TI  - Feasibility study of a randomised controlled trial to investigate the treatment
      of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study
      protocol.
AB  - INTRODUCTION: Fatigue is a frequent and troublesome manifestation of chronic
      sarcoidosis. This symptom can be debilitating and difficult to treat, with poor
      response to the treatment. Symptomatic management with neurostimulants, such as
      methylphenidate, is a possible treatment option. The use of such treatment
      strategies is not without precedent and has been trialled in cancer-related
      fatigue. Their use in sarcoidosis requires further evaluation before it can be
      recommended for clinical practice. METHODS AND ANALYSIS: The Fatigue and
      Sarcoidosis-Treatment with Methylphenidate study is a randomised, controlled,
      parallel-arm and feasibility trial of methylphenidate for the treatment of
      sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of
      sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale)
      and have stable disease. Up to 30 participants will be randomly assigned to
      either methylphenidate (20 mg two times per day) or identical placebo in a 3:2
      ratio for 24 weeks. The primary objective is to collect data determining the
      feasibility of a future study powered to determine the clinical efficacy of
      methylphenidate for sarcoidosis-associated fatigue. The trial is presently open
      and will continue until July 2018. ETHICS AND DISSEMINATION: Ethical approval for
      the study was granted by the Cambridge Central Research Ethics Committee on 21
      June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk
      and Norwich University Hospital (reference 190280). Clinical Trial Authorisation
      (EudraCT number 2016-000342-60) from the Medicines and Healthcare products
      Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented
      at relevant conferences and submitted to appropriate journals following trial
      closure and analysis. TRIAL REGISTRATION NUMBER: NCT02643732; Pre-results.

PMID- 29208617
TI  - Stigma towards mental illness among medical and nursing students in Singapore: a
      cross-sectional study.
AB  - OBJECTIVES: To assess stigma towards people with mental illness among Singapore
      medical and nursing students using the Opening Minds Stigma Scale for Health Care
      Providers (OMS-HC), and to examine the relationship of students' stigmatising
      attitudes with sociodemographic and education factors. DESIGN AND SETTING: Cross
      sectional study conducted in Singapore PARTICIPANTS: The study was conducted
      among 1002 healthcare (502 medical and 500 nursing) students during April to
      September 2016. Students had to be Singapore citizens or permanent residents and
      enrolled in public educational institutions to be included in the study. The mean
      (SD) age of the participants was 21.3 (3.3) years, with the majority being
      females (71.1%). 75.2% of the participants were Chinese, 14.1% were Malays, and
      10.7% were either Indians or of other ethnicity. METHODS: Factor analysis was
      conducted to validate the OMS-HC scale in the study sample and to examine its
      factor structure. Descriptive statistics and multivariate linear regression were
      used to examine sociodemographic and education correlates. RESULTS: Factor
      analysis revealed a three-factor structure with 14 items. The factors were
      labelled as attitudes towards help-seeking and people with mental illness, social
      distance and disclosure. Multivariable linear regression analysis showed that
      medical students were found to be associated with lower total OMS-HC scores
      (P<0.05), less negative attitudes (P<0.001) and greater disclosure (P<0.05) than
      nursing students. Students who had a monthly household income of below S$4000 had
      more unfavourable attitudes than those with an income of SGD$10 000 and above
      (P<0.05). Having attended clinical placement was associated with more negative
      attitudes (P<0.05) among the students. CONCLUSION: Healthcare students generally
      possessed positive attitudes towards help-seeking and persons with mental
      illness, though they preferred not to disclose their own mental health condition.
      Academic curriculum may need to enhance the component of mental health training,
      particularly on reducing stigma in certain groups of students.

PMID- 29208619
TI  - Encouraging translation and assessing impact of the Centre for Research
      Excellence in Integrated Quality Improvement: rationale and protocol for a
      research impact assessment.
AB  - INTRODUCTION: There is growing recognition among health researchers and funders
      that the wider benefits of research such as economic, social and health impacts
      ought to be assessed and valued alongside academic outputs such as peer-reviewed
      papers. Research translation needs to increase and the pathways to impact ought
      to be more transparent. These processes are particularly pertinent to the
      Indigenous health sector given continued concerns that Indigenous communities are
      over-researched with little corresponding improvement in health outcomes. This
      paper describes the research protocol of a mixed methods study to apply FAIT
      (Framework to Assess the Impact from Translational health research) to the Centre
      for Research Excellence in Integrated Quality Improvement (CRE-IQI). FAIT will be
      applied to five selected CRE-IQI Flagship projects to encourage research
      translation and assess the wider impact of that research. METHODS AND ANALYSIS:
      Phase I will develop a modified programme logic model for each Flagship project
      including identifying process, output and impact metrics so progress can be
      monitored. A scoping review will inform potential benefits. In phase II,
      programme logic models will be updated to account for changes in the research
      pathways over time. Audit and feedback will be used to encourage research
      translation and collect evidence of achievement of any process, output and
      interim impacts. In phase III, three proven methodologies for measuring research
      impact-Payback, economic assessment and narratives-will be applied. Data on the
      application of FAIT will be collected and analysed to inform and improve FAIT's
      performance. ETHICS AND DISSEMINATION: This study is funded by a nationally
      competitive grant (ID 1078927) from the Australian National Health and Medical
      Research Council. Ethics approval was obtained from the University of Newcastle's
      Human Research Ethics Committee (ID: H-2017-0026). The results from the study
      will be presented in several peer-reviewed publications, through conference
      presentations and via social media.

PMID- 29208620
TI  - Impact of electronic clinical decision support on adherence to guideline
      recommended treatment for hyperlipidaemia, atrial fibrillation and heart failure:
      protocol for a cluster randomised trial.
AB  - INTRODUCTION: Clinical practice guidelines facilitate optimal clinical practice.
      Point of care access, interpretation and application of such guidelines, however,
      is inconsistent. Informatics-based tools may help clinicians apply guidelines
      more consistently. We have developed a novel clinical decision support tool that
      presents guideline-relevant information and actionable items to clinicians at the
      point of care. We aim to test whether this tool improves the management of
      hyperlipidaemia, atrial fibrillation and heart failure by primary care
      clinicians. METHODS/ANALYSIS: Clinician care teams were cluster randomised to
      receive access to the clinical decision support tool or passive access to
      institutional guidelines on 16 May 2016. The trial began on 1 June 2016 when
      access to the tool was granted to the intervention clinicians. The trial will be
      run for 6 months to ensure a sufficient number of patient encounters to achieve
      80% power to detect a twofold increase in the primary outcome at the 0.05 level
      of significance. The primary outcome measure will be the percentage of guideline
      based recommendations acted on by clinicians for hyperlipidaemia, atrial
      fibrillation and heart failure. We hypothesise care teams with access to the
      clinical decision support tool will act on recommendations at a higher rate than
      care teams in the standard of care arm. ETHICS AND DISSEMINATION: The Mayo Clinic
      Institutional Review Board approved all study procedures. Informed consent was
      obtained from clinicians. A waiver of informed consent and of Health Insurance
      Portability and Accountability Act (HIPAA) authorisation for patients managed by
      clinicians in the study was granted. In addition to publication, results will be
      disseminated via meetings and newsletters. TRIAL REGISTRATION NUMBER:
      NCT02742545.

PMID- 29208622
TI  - US tax bill could destroy central pillar of Obamacare.

PMID- 29208621
TI  - Retrospective, multicohort analysis of the Clinical Practice Research Datalink
      (CPRD) to determine differences in the cost of medication wastage, dispensing
      fees and prescriber time of issuing either short (<60 days) or long (>=60 days)
      prescription lengths in primary care for common, chronic conditions in the UK.
AB  - OBJECTIVES: To investigate patterns of early repeat prescriptions and treatment
      switching over an 11-year period to estimate differences in the cost of
      medication wastage, dispensing fees and prescriber time for short (<60 days) and
      long (>=60 days) prescription lengths from the perspective of the National Health
      Service in the UK. SETTING: Retrospective, multiple cohort study of primary care
      prescriptions from the Clinical Practice Research Datalink. PARTICIPANTS: Five
      random samples of 50 000 patients each prescribed oral drugs for (1) glucose
      control in type 2 diabetes mellitus (T2DM); (2) hypertension in T2DM; (3) statins
      (lipid management) in T2DM; (4) secondary prevention of myocardial infarction;
      and (5) depression. PRIMARY AND SECONDARY OUTCOME MEASURES: The volume of
      medication wastage from early repeat prescriptions and three other types of
      treatment switches was quantified and costed. Dispensing fees and prescriber time
      were also determined. Total unnecessary costs (TUC; cost of medication wastage,
      dispensing fees and prescriber time) associated with <60 day and >=60 day
      prescriptions, standardised to a 120-day period, were then compared. RESULTS:
      Longer prescription lengths were associated with more medication waste per
      prescription. However, when including dispensing fees and prescriber time, longer
      prescription lengths resulted in lower TUC. This finding was consistent across
      all five cohorts. Savings ranged from L8.38 to L12.06 per prescription per 120
      days if a single long prescription was issued instead of multiple short
      prescriptions. Prescriber time costs accounted for the largest component of TUC.
      CONCLUSIONS: Shorter prescription lengths could potentially reduce medication
      wastage, but they may also increase dispensing fees and/or the time burden of
      issuing prescriptions.

PMID- 29208623
TI  - Acknowledgment of Ad Hoc Reviewers.

PMID- 29208625
TI  - Lowering Expectations with Niacin Treatment for CKD-MBD.

PMID- 29208626
TI  - The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.
AB  - BACKGROUND AND OBJECTIVES: Niacin downregulates intestinal sodium-dependent
      phosphate transporter 2b expression and reduces intestinal phosphate transport.
      Short-term studies have suggested that niacin lowers serum phosphate
      concentrations in patients with CKD and ESRD. However, the long-term effects of
      niacin on serum phosphate and other mineral markers are unknown. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The Atherothrombosis Intervention in Metabolic
      Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a
      randomized, double-blind, placebo-controlled trial testing extended release
      niacin in persons with prevalent cardiovascular disease. We examined the effect
      of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal
      changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min
      per 1.73 m2 over 3 years. Changes in each marker were compared over time between
      the niacin and placebo arms using linear mixed effects models. RESULTS:
      Randomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations
      per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean
      phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast,
      randomization to niacin was not associated with statistically significant changes
      in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or
      vitamin D metabolites over 3 years. CONCLUSIONS: The use of niacin over 3 years
      lowered serum phosphorous concentrations but did not affect other markers of
      mineral metabolism in participants with CKD.

PMID- 29208627
TI  - Generation and characterisation of two D2A1 mammary cancer sublines to model
      spontaneous and experimental metastasis in a syngeneic BALB/c host.
AB  - Studying the complex mechanisms underlying breast cancer metastasis and therapy
      response necessitates relevant in vivo models, particularly syngeneic models with
      an intact immune system. Two syngeneic spontaneously metastatic sublines, D2A1-m1
      and D2A1-m2, were generated from the poorly metastasising BALB/c-derived D2A1
      cell line by serial in vivo passaging. In vivo and in vitro analyses revealed
      distinct and shared characteristics of the metastatic D2A1-m1 and D2A1-m2
      sublines. In particular, D2A1-m1 cells are more aggressive in experimental
      metastasis assays, while D2A1-m2 cells are more efficient at disseminating from
      the primary tumour in spontaneous metastasis assays. Surprisingly, classical
      metastasis-associated in vitro phenotypes, such as enhanced proliferation,
      migration and invasion, are reduced in the sublines compared to the parental cell
      line. Further, evasion of immune control cannot fully explain their enhanced
      metastatic properties. By contrast, both sublines show increased resistance to
      apoptosis when cultured in non-adherent conditions and, for the D2A1-m2 subline,
      increased 3D tumour spheroid growth. Moreover, the enhanced spontaneous
      metastatic phenotype of the D2A1-m2 subline is associated with an increased
      ability to recruit an activated tumour stroma. The metastatic D2A1-m1 and D2A1-m2
      cell lines provide additional syngeneic models for investigating the different
      steps of the metastatic cascade and thereby represent valuable tools for breast
      cancer researchers. Finally, this study highlights that morphology and cell
      behaviour in 2D cell-based assays cannot be used as a reliable predictor of
      metastatic behaviour in vivo.

PMID- 29208628
TI  - Impact of regulatory variation across human iPSCs and differentiated cells.
AB  - Induced pluripotent stem cells (iPSCs) are an essential tool for studying
      cellular differentiation and cell types that are otherwise difficult to access.
      We investigated the use of iPSCs and iPSC-derived cells to study the impact of
      genetic variation on gene regulation across different cell types and as models
      for studies of complex disease. To do so, we established a panel of iPSCs from 58
      well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were
      further differentiated into cardiomyocytes. We characterized regulatory variation
      across individuals and cell types by measuring gene expression levels, chromatin
      accessibility, and DNA methylation. Our analysis focused on a comparison of inter
      individual regulatory variation across cell types. While most cell-type-specific
      regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in
      the affected cell types, we found that 20% of cell-type-specific regulatory QTLs
      are in shared open chromatin. This observation motivated us to develop a deep
      neural network to predict open chromatin regions from DNA sequence alone. Using
      this approach, we were able to use the sequences of segregating haplotypes to
      predict the effects of common SNPs on cell-type-specific chromatin accessibility.

PMID- 29208629
TI  - SIDR: simultaneous isolation and parallel sequencing of genomic DNA and total RNA
      from single cells.
AB  - Simultaneous sequencing of the genome and transcriptome at the single-cell level
      is a powerful tool for characterizing genomic and transcriptomic variation and
      revealing correlative relationships. However, it remains technically challenging
      to analyze both the genome and transcriptome in the same cell. Here, we report a
      novel method for simultaneous isolation of genomic DNA and total RNA (SIDR) from
      single cells, achieving high recovery rates with minimal cross-contamination, as
      is crucial for accurate description and integration of the single-cell genome and
      transcriptome. For reliable and efficient separation of genomic DNA and total RNA
      from single cells, the method uses hypotonic lysis to preserve nuclear lamina
      integrity and subsequently captures the cell lysate using antibody-conjugated
      magnetic microbeads. Evaluating the performance of this method using real-time
      PCR demonstrated that it efficiently recovered genomic DNA and total RNA.
      Thorough data quality assessments showed that DNA and RNA simultaneously
      fractionated by the SIDR method were suitable for genome and transcriptome
      sequencing analysis at the single-cell level. The integration of single-cell
      genome and transcriptome sequencing by SIDR (SIDR-seq) showed that genetic
      alterations, such as copy-number and single-nucleotide variations, were more
      accurately captured by single-cell SIDR-seq compared with conventional single
      cell RNA-seq, although copy-number variations positively correlated with the
      corresponding gene expression levels. These results suggest that SIDR-seq is
      potentially a powerful tool to reveal genetic heterogeneity and phenotypic
      information inferred from gene expression patterns at the single-cell level.

PMID- 29208630
TI  - Regulated Alternative Splicing of Drosophila Dscam2 Is Necessary for Attaining
      the Appropriate Number of Photoreceptor Synapses.
AB  - How the brain makes trillions of synaptic connections using a genome of only
      20,000 genes is a major question in modern neuroscience. Alternative splicing is
      one mechanism that can increase the number of proteins produced by each gene, but
      its role in regulating synapse formation is poorly understood. In Drosophila,
      photoreceptors form a synapse with multiple postsynaptic elements including
      lamina neurons L1 and L2. L1 and L2 express distinct isoforms of the homophilic
      repulsive protein Dscam2, and since these isoforms cannot bind to each other,
      cell-specific expression has been proposed to be necessary for preventing
      repulsive interactions that could disrupt the synapse. Here, we show that the
      number of synapses are reduced in flies that express only one isoform, and L1 and
      L2 dendritic morphology is perturbed. We propose that these defects result from
      inappropriate interactions between L1 and L2 dendrites. We conclude that
      regulated Dscam2 alternative splicing is necessary for the proper assembly of
      photoreceptor synapses.

PMID- 29208632
TI  - Right ventricular exercise contractile reserve and outcomes after early surgery
      for primary mitral regurgitation.
AB  - OBJECTIVE: To assess if the lack of development of right ventricular (RV)
      contractile reserve during exercise echocardiography (ex-echo) might be a
      predictor of postoperative major adverse cardiovascular events (MACEs) in
      patients with primary mitral regurgitation (pMR) undergoing early surgery.
      METHODS: Comprehensive resting and ex-echo were performed in 142 asymptomatic
      patients (58+/-21 years, 68% men, New York Heart Association functional class
      <=2) with isolated severe pMR and preserved left ventricular (LV) function (LV
      ejection >60%, LV end-systolic diameter <45 mm) undergoing mitral valve
      replacement (n=20) or repair. Postoperative MACEs were defined as occurrence of
      atrial fibrillation, stroke, cardiac-related hospitalisation or death. RV
      function was evaluated at rest in every patient during ex-echo by measuring their
      tricuspid annular plane systolic excursion (TAPSE) value. RESULTS: After median
      follow-up of 30 months (IQR 16-60 months), MACEs occurred in 48 (34%) patients.
      Using Bayesian model averaging, among all the characteristics including the type
      of surgery, exercise TAPSE (ex-TAPSE) emerged as the most likely predictor of
      prognosis (HR 0.91, 95% CI 0.86 to 0.96). Other probable predictors were exercise
      fractional area change (HR 0.02, 95% CI 0.00 to 0.80), male gender (HR 0.40, 95%
      CI 0.21 to 0.75) and RV basal diameter (HR 1.06, 95% CI 0.98 to 1.14). In the
      receiver operating characteristic curve analysis, an ex-TAPSE value of <26 mm
      (sensitivity 73% (95% CI 61 to 84) and specificity of 86% (95% CI 77% to 93%))
      defined RV dysfunction. Event-free survival at 5 years was significantly lower in
      the patient group that exhibited no development of RV contractile reserve during
      exercise: 43.9% (95% CI 31.3 to 61.4) vs 75.8% (95% CI 64.8 to 88.7). CONCLUSION:
      Lack of development of exercise-induced RV contractile reserve is a prognostic
      predictor in patients with severe pMR undergoing early mitral valve surgery.

PMID- 29208631
TI  - The Drosophila junctophilin gene is functionally equivalent to its four mammalian
      counterparts and is a modifier of a Huntingtin poly-Q expansion and the Notch
      pathway.
AB  - Members of the Junctophilin (JPH) protein family have emerged as key actors in
      all excitable cells, with crucial implications for human pathophysiology. In
      mammals, this family consists of four members (JPH1-JPH4) that are differentially
      expressed throughout excitable cells. The analysis of knockout mice lacking JPH
      subtypes has demonstrated their essential contribution to physiological functions
      in skeletal and cardiac muscles and in neurons. Moreover, mutations in the human
      JPH2 gene are associated with hypertrophic and dilated cardiomyopathies;
      mutations in JPH3 are responsible for the neurodegenerative Huntington's disease
      like-2 (HDL2), whereas JPH1 acts as a genetic modifier in Charcot-Marie-Tooth 2K
      peripheral neuropathy. Drosophila melanogaster has a single junctophilin (jp)
      gene, as is the case in all invertebrates, which might retain equivalent
      functions of the four homologous JPH genes present in mammalian genomes.
      Therefore, owing to the lack of putatively redundant genes, a jpDrosophila model
      could provide an excellent platform to model the Junctophilin-related diseases,
      to discover the ancestral functions of the JPH proteins and to reveal new
      pathways. By up- and downregulation of Jp in a tissue-specific manner in
      Drosophila, we show that altering its levels of expression produces a phenotypic
      spectrum characterized by muscular deficits, dilated cardiomyopathy and neuronal
      alterations. Importantly, our study has demonstrated that Jp modifies the
      neuronal degeneration in a Drosophila model of Huntington's disease, and it has
      allowed us to uncover an unsuspected functional relationship with the Notch
      pathway. Therefore, this Drosophila model has revealed new aspects of
      Junctophilin function that can be relevant for the disease mechanisms of their
      human counterparts.

PMID- 29208633
TI  - In Vivo Visualization of beta-Cells by Targeting of GPR44.
AB  - GPR44 expression has recently been described as highly beta-cell selective in the
      human pancreas and constitutes a tentative surrogate imaging biomarker in
      diabetes. A radiolabeled small-molecule GPR44 antagonist, [11C]AZ12204657, was
      evaluated for visualization of beta-cells in pigs and nonhuman primates by
      positron emission tomography as well as in immunodeficient mice transplanted with
      human islets under the kidney capsule. In vitro autoradiography of human and
      animal pancreatic sections from subjects without and with diabetes, in
      combination with insulin staining, was performed to assess beta-cell selectivity
      of the radiotracer. Proof of principle of in vivo targeting of human islets by
      [11C]AZ12204657 was shown in the immunodeficient mouse transplantation model.
      Furthermore, [11C]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic
      sections from humans and pigs without diabetes, but not those with diabetes. In
      vivo [11C]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could
      be competed away dose-dependently in nondiabetic pigs and nonhuman primates.
      [11C]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic
      beta-cells by targeting the protein GPR44.

PMID- 29208634
TI  - The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With
      Streptozotocin-Induced Diabetes.
AB  - BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have antiapoptotic
      properties via mechanisms involving the nerve growth factor receptors
      (tropomyosin-related kinase A [TrkA]/neurotrophin receptor p75 [p75NTR]). In this
      study, we examined the effects of BNN27 on neural/glial cell function, apoptosis,
      and inflammation in the experimental rat streptozotocin (STZ) model of diabetic
      retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate
      p75NTR expression was investigated. BNN27 (2,10, and 50 mg/kg i.p. for 7 days)
      administration 4 weeks post-STZ injection (paradigm A) reversed the diabetes
      induced glial activation and loss of function of amacrine cells (brain nitric
      oxide synthetase/tyrosine hydroxylase expression) and ganglion cell axons via a
      TrkA receptor (TrkAR)-dependent mechanism. BNN27 activated/phosphorylated the
      TrkAY490 residue in the absence but not the presence of TrkAR inhibitor and
      abolished the diabetes-induced increase in p75NTR expression. However, it had no
      effect on retinal cell death (TUNEL+ cells). A similar result was observed when
      BNN27 (10 mg/kg i.p.) was administered at the onset of diabetes, every other day
      for 4 weeks (paradigm B). However, BNN27 decreased the activation of caspase-3 in
      both paradigms. Finally, BNN27 reduced the proinflammatory (TNFalpha and IL
      1beta) and increased the anti-inflammatory (IL-10 and IL-4) cytokine levels.
      These findings suggest that BNN27 has the pharmacological profile of a
      therapeutic for DR, since it targets both the neurodegenerative and inflammatory
      components of the disease.

PMID- 29208635
TI  - The Sox2 promoter-driven CD63-GFP transgenic rat model allows tracking of neural
      stem cell-derived extracellular vesicles.
AB  - Extracellular vesicles (EVs) can modulate microenvironments by transferring
      biomolecules, including RNAs and proteins derived from releasing cells, to target
      cells. To understand the molecular mechanisms maintaining the neural stem cell
      (NSC) niche through EVs, a new transgenic (Tg) rat strain that can release human
      CD63-GFP-expressing EVs from the NSCs was established. Human CD63-GFP expression
      was controlled under the rat Sox2 promoter (Sox2/human CD63-GFP), and it was
      expressed in undifferentiated fetal brains. GFP signals were specifically
      observed in in vitro cultured NSCs obtained from embryonic brains of the Tg rats.
      We also demonstrated that embryonic NSC (eNSC)-derived EVs were labelled by human
      CD63-GFP. Furthermore, when we examined the transfer of EVs, eNSC-derived EVs
      were found to be incorporated into astrocytes and eNSCs, thus implying an EV
      mediated communication between different cell types around NSCs. This new
      Sox2/human CD63-GFP Tg rat strain should provide resources to analyse the cell-to
      cell communication via EVs in NSC microenvironments.

PMID- 29208637
TI  - Could blocking the formation of amyloid channels rescue Alzheimer's phenotype?

PMID- 29208636
TI  - Homeodomain-interacting protein kinase promotes tumorigenesis and metastatic cell
      behavior.
AB  - Aberrations in signaling pathways that regulate tissue growth often lead to
      tumorigenesis. Homeodomain-interacting protein kinase (Hipk) family members are
      reported to have distinct and contradictory effects on cell proliferation and
      tissue growth. From these studies, it is clear that much remains to be learned
      about the roles of Hipk family protein kinases in proliferation and cell
      behavior. Previous work has shown that Drosophila Hipk is a potent growth
      regulator, thus we predicted that it could have a role in tumorigenesis. In our
      study of Hipk-induced phenotypes, we observed the formation of tumor-like
      structures in multiple cell types in larvae and adults. Furthermore, elevated
      Hipk in epithelial cells induces cell spreading, invasion and epithelial-to
      mesenchymal transition (EMT) in the imaginal disc. Further evidence comes from
      cell culture studies, in which we expressed Drosophila Hipk in human breast
      cancer cells and showed that it enhances proliferation and migration. Past
      studies have shown that Hipk can promote the action of conserved pathways
      implicated in cancer and EMT, such as Wnt/Wingless, Hippo, Notch and JNK. We show
      that Hipk phenotypes are not likely to arise from activation of a single target,
      but rather through a cumulative effect on numerous target pathways. Most
      Drosophila tumor models involve mutations in multiple genes, such as the well
      known RasV12 model, in which EMT and invasiveness occur after the additional loss
      of the tumor suppressor gene scribble. Our study reveals that elevated levels of
      Hipk on their own can promote both hyperproliferation and invasive cell behavior,
      suggesting that Hipk family members could be potent oncogenes and drivers of EMT.

PMID- 29208639
TI  - Reconstitution of Female Germ Cell Fate Determination and Meiotic Initiation in
      Mammals.
AB  - Meiosis is a fundamental process that underpins sexual reproduction. In mammals,
      the execution of meiosis is tightly integrated within the complex processes of
      oogenesis and spermatogenesis, and elucidation of the molecular mechanisms
      regulating meiotic initiation remains challenging. We have recently developed in
      vitro culture strategies to induce mouse pluripotent stem cells into germ cells,
      which successfully contribute to both oogenesis and spermatogenesis and to
      fertile offspring. The culture strategies faithfully recapitulate transcriptional
      and epigenetic dynamics as well as signaling principles for germ cell
      specification, proliferation, and female sex determination/meiotic induction,
      providing a valuable platform for studies to illuminate the molecular mechanisms
      underlying such critical processes. Here, we review mammalian gametogenesis with
      a focus on the implementation of meiosis and, based on our recent studies,
      discuss new insights into the mechanisms for meiotic initiation and germ cell sex
      determination in mice.

PMID- 29208640
TI  - Shaping Chromatin in the Nucleus: The Bricks and the Architects.
AB  - Chromatin organization in the nucleus provides a vast repertoire of information
      in addition to that encoded genetically. Understanding how this organization
      impacts genome stability and influences cell fate and tumorigenesis is an area of
      rapid progress. Considering the nucleosome, the fundamental unit of chromatin
      structure, the study of histone variants (the bricks) and their selective loading
      by histone chaperones (the architects) is particularly informative. Here, we
      report recent advances in understanding how relationships between histone
      variants and their chaperones contribute to tumorigenesis using cell lines and
      Xenopus development as model systems. In addition to their role in histone
      deposition, we also document interactions between histone chaperones and other
      chromatin factors that govern higher-order structure and control DNA metabolism.
      We highlight how a fine-tuned assembly line of bricks (H3.3 and CENP-A) and
      architects (HIRA, HJURP, and DAXX) is key in adaptation to developmental and
      pathological changes. An example of this conceptual advance is the exquisite
      sensitivity displayed by p53-null tumor cells to modulation of HJURP, the histone
      chaperone for CENP-A (CenH3 variant). We discuss how these findings open avenues
      for novel therapeutic paradigms in cancer care.

PMID- 29208638
TI  - The diphenylpyrazole compound anle138b blocks Abeta channels and rescues disease
      phenotypes in a mouse model for amyloid pathology.
AB  - Alzheimer's disease is a devastating neurodegenerative disease eventually leading
      to dementia. An effective treatment does not yet exist. Here we show that oral
      application of the compound anle138b restores hippocampal synaptic and
      transcriptional plasticity as well as spatial memory in a mouse model for
      Alzheimer's disease, when given orally before or after the onset of pathology. At
      the mechanistic level, we provide evidence that anle138b blocks the activity of
      conducting Abeta pores without changing the membrane embedded Abeta-oligomer
      structure. In conclusion, our data suggest that anle138b is a novel and promising
      compound to treat AD-related pathology that should be investigated further.

PMID- 29208642
TI  - STPs are based on flawed financial assumptions.

PMID- 29208641
TI  - Alternative Oxidase Isoforms Are Differentially Activated by Tricarboxylic Acid
      Cycle Intermediates.
AB  - The cyanide-insensitive alternative oxidase (AOX) is a non-proton-pumping
      ubiquinol oxidase that catalyzes the reduction of oxygen to water and is
      posttranslationally regulated by redox mechanisms and 2-oxo acids. Arabidopsis
      (Arabidopsis thaliana) possesses five AOX isoforms (AOX1A-AOX1D and AOX2). AOX1D
      expression is increased in aox1a knockout mutants from Arabidopsis (especially
      after restriction of the cytochrome c pathway) but cannot compensate for the lack
      of AOX1A, suggesting a difference in the regulation of these isoforms. Therefore,
      we analyzed the different AOX isoenzymes with the aim to identify differences in
      their posttranslational regulation. Seven tricarboxylic acid cycle intermediates
      (citrate, isocitrate, 2-oxoglutarate, succinate, fumarate, malate, and
      oxaloacetate) were tested for their influence on AOX1A, AOX1C, and AOX1D wild
      type protein activity using a refined in vitro system. AOX1C is insensitive to
      all seven organic acids, AOX1A and AOX1D are both activated by 2-oxoglutarate,
      but only AOX1A is additionally activated by oxaloacetate. Furthermore, AOX
      isoforms cannot be transformed to mimic one another by substituting the variable
      cysteine residues at position III in the protein. In summary, we show that AOX
      isoforms from Arabidopsis are differentially fine-regulated by tricarboxylic acid
      cycle metabolites (most likely depending on the amino-terminal region around the
      highly conserved cysteine residues known to be involved in regulation by the 2
      oxo acids pyruvate and glyoxylate) and propose that this is the main reason why
      they cannot functionally compensate for each other.

PMID- 29208643
TI  - Heterologous Protein Expression in the Xenopus Oocyte.
AB  - The Xenopus oocyte is a specialized single cell of colossal size (>1 mm diameter)
      that is highly amenable for microinjection and a stalwart model for heterologous
      expression. Oocytes are easily obtainable, robust in vitro, and faithfully
      express injected constructs. Their large size translational capacity provides a
      huge canvas for observing and recording integrated cellular responses-from
      studies of single molecules within single cells to medium-throughput drug
      screening applications. Most eukaryotic promoters suffice for Xenopus expression,
      and the oocyte can functionally express proteins from many diverse organisms.
      This protocol provides a basic introduction for scientists keen to perform
      nuclear microinjections of cDNA constructs. These are easy methods to master, do
      not require elaborate equipment, and make accessible a wonderful model cell
      system for studying signaling, transport, cell architecture, and protein
      function.

PMID- 29208644
TI  - Filopodia-Like Structure Formation from Xenopus Egg Extracts.
AB  - The actin cytoskeleton comprises many different architectures of filaments,
      including branched networks, parallel bundles and antiparallel fibers. A current
      challenge is to elucidate how the diverse array of actin regulators, which
      controls the growth, assembly and turnover of actin filaments, is used to
      orchestrate cytoskeletal organization and in turn cell shape and movement. Long
      observed to assemble at cell membranes, actin in Xenopus egg extracts
      recapitulates membrane-triggered assembly at specific lipid and membrane
      environments. The use of Xenopus egg extracts has contributed greatly to
      identifying how constitutively autoinhibited regulatory pathways are activated,
      which converge on activation of the Arp2/3 complex. Here we describe a protocol
      for making parallel actin bundles using Xenopus egg extracts from supernatants
      prepared by high-speed centrifugation. These filopodia-like actin bundles emanate
      from clusters of actin regulators that self-assemble at phosphatidylinositol
      (4,5)-bisphosphate-containing supported lipid bilayers. Forming a plasma membrane
      mimicking bilayer on glass allows easy, optimizable, high signal-to-noise
      microscopy at high spatial and temporal resolution. The use of Xenopus egg
      extracts yields large quantities of active material that can be flexibly tailored
      to address specific questions, for example, by dilution, addition of fluorescent
      proteins, antibodies or protein fragments, immunodepletion, addition of small
      molecule inhibitors, or biochemical fractionation.

PMID- 29208645
TI  - Observation of DNA intertwining along authentic budding yeast chromosomes.
AB  - DNA replication of circular genomes generates physically interlinked or catenated
      sister DNAs. These are resolved through transient DNA fracture by type II
      topoisomerases to permit chromosome segregation during cell division.
      Topoisomerase II is similarly required for linear chromosome segregation,
      suggesting that linear chromosomes also remain intertwined following DNA
      replication. Indeed, chromosome resolution defects are a frequent cause of
      chromosome segregation failure and consequent aneuploidies. When and where
      intertwines arise and persist along linear chromosomes are not known, owing to
      the difficulty of demonstrating intertwining of linear DNAs. Here, we used
      excision of chromosomal regions as circular "loop outs" to convert sister
      chromatid intertwines into catenated circles. This revealed intertwining at
      replication termination and cohesin-binding sites, where intertwines are thought
      to arise and persist but not to a greater extent than elsewhere in the genome.
      Intertwining appears to spread evenly along chromosomes but is excluded from
      heterochromatin. We found that intertwines arise before replication termination,
      suggesting that replication forks rotate during replication elongation to
      dissipate torsion ahead of the forks. Our approach provides previously
      inaccessible insight into the topology of eukaryotic chromosomes and illuminates
      a process critical for successful chromosome segregation.

PMID- 29208646
TI  - A Serum Protein Signature Associated with Outcome after Anti-PD-1 Therapy in
      Metastatic Melanoma.
AB  - A mass spectrometry analysis was performed using serum from patients receiving
      checkpoint inhibitors to define baseline protein signatures associated with
      outcome in metastatic melanoma. Pretreatment serum was obtained from a
      development set of 119 melanoma patients on a trial of nivolumab with or without
      a multipeptide vaccine and from patients receiving pembrolizumab, nivolumab,
      ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix
      assisted laser desorption/ionization time of flight mass spectrometry. These data
      combined with clinical data identified patients with better or worse outcomes.
      The test was applied to five independent patient cohorts treated with checkpoint
      inhibitors and its biology investigated using enrichment analyses. A signature
      consisting of 209 proteins or peptides was associated with progression-free and
      overall survival in a multivariate analysis. The test performance across
      validation cohorts was consistent with the development set results. A pooled
      analysis, stratified by set, demonstrated a significantly better overall survival
      for "sensitive" relative to "resistant" patients, HR = 0.15 (95% confidence
      interval: 0.06-0.40, P < 0.001). The test was also associated with survival in a
      cohort of ipilimumab-treated patients. Test classification was found to be
      associated with acute phase reactant, complement, and wound healing pathways. We
      conclude that a pretreatment signature of proteins, defined by mass spectrometry
      analysis and machine learning, predicted survival in patients receiving PD-1
      blocking antibodies. This signature of proteins was associated with acute phase
      reactants and elements of wound healing and the complement cascade. This
      signature merits further study to determine if it identifies patients who would
      benefit from PD-1 blockade. Cancer Immunol Res; 6(1); 79-86. (c)2017 AACR.

PMID- 29208648
TI  - Optimizing Genomic Methods for Mapping and Identification of Candidate Variants
      in ENU Mutagenesis Screens Using Inbred Mice.
AB  - Positional cloning of ENU-induced mutations has traditionally relied on analysis
      of polymorphic variation between two strains. In contrast, the application of
      whole-genome sequencing (WGS) has enabled gene discovery in mutant lines
      maintained on an inbred genetic background. This approach utilizes genetic
      variation derived from ENU-induced variants for mapping and reduces the
      likelihood of phenotypic variation, making it an ideal method for genetic
      modifier screening. Here, we describe the results of such a screen, wherein we
      determined the minimal number of mutant genomic DNA samples to include in our
      analyses and improved the sensitivity of our screen by individually barcoding
      each genomic DNA library. We present several unique cases to illustrate this
      approach's efficacy, including the discovery of two distinct mutations that
      generate essentially identical mutant phenotypes, the ascertainment of a non-ENU
      induced candidate variant through homozygosity mapping, and an approach for the
      identification of putative dominant genetic modifiers.

PMID- 29208649
TI  - Whole Genome Sequencing of Hulunbuir Short-Tailed Sheep for Identifying Candidate
      Genes Related to the Short-Tail Phenotype.
AB  - The Hulunbuir short-tailed sheep (Ovis aries) is a breed native to China, in
      which the short-tail phenotype is the result of artificial and natural selection
      favoring a specific set of genetic mutations. Here, we analyzed the genetic
      differences between short-tail and normal-tail phenotypes at the genomic level.
      Selection signals were identified in genome-wide sequences. From 16 sheep, we
      identified 72,101,346 single nucleotide polymorphisms. Selection signals were
      detected based on the fixation index and heterozygosity. Seven genomic regions
      under putative selection were identified, and these regions contained nine genes.
      Among these genes, T was the strongest candidate as T is related to vertebral
      development. In T, a nonsynonymous mutation at c.G334T resulted in p.G112W
      substitution. We inferred that the c.G334T mutation in T leads to functional
      changes in Brachyury-encoded by this gene-resulting in the short-tail phenotype.
      Our findings provide a valuable insight into the development of the short-tail
      phenotype in sheep and other short-tailed animals.

PMID- 29208647
TI  - Cell-Type Transcriptomes of the Multicellular Green Alga Volvox carteri Yield
      Insights into the Evolutionary Origins of Germ and Somatic Differentiation
      Programs.
AB  - Germ-soma differentiation is a hallmark of complex multicellular organisms, yet
      its origins are not well understood. Volvox carteri is a simple multicellular
      green alga that has recently evolved a simple germ-soma dichotomy with only two
      cell-types: large germ cells called gonidia and small terminally differentiated
      somatic cells. Here, we provide a comprehensive characterization of the gonidial
      and somatic transcriptomes of V. carteri to uncover fundamental differences
      between the molecular and metabolic programming of these cell-types. We found
      extensive transcriptome differentiation between cell-types, with somatic cells
      expressing a more specialized program overrepresented in younger, lineage
      specific genes, and gonidial cells expressing a more generalist program
      overrepresented in more ancient genes that shared striking overlap with stem cell
      specific genes from animals and land plants. Directed analyses of different
      pathways revealed a strong dichotomy between cell-types with gonidial cells
      expressing growth-related genes and somatic cells expressing an altruistic
      metabolic program geared toward the assembly of flagella, which support
      organismal motility, and the conversion of storage carbon to sugars, which act as
      donors for production of extracellular matrix (ECM) glycoproteins whose secretion
      enables massive organismal expansion. V. carteri orthologs of diurnally
      controlled genes from C. reinhardtii, a single-celled relative, were analyzed for
      cell-type distribution and found to be strongly partitioned, with expression of
      dark-phase genes overrepresented in somatic cells and light-phase genes
      overrepresented in gonidial cells- a result that is consistent with cell-type
      programs in V. carteri arising by cooption of temporal regulons in a unicellular
      ancestor. Together, our findings reveal fundamental molecular, metabolic, and
      evolutionary mechanisms that underlie the origins of germ-soma differentiation in
      V. carteri and provide a template for understanding the acquisition of germ-soma
      differentiation in other multicellular lineages.

PMID- 29208650
TI  - Transcriptional Profiling of Saccharomyces cerevisiae Reveals the Impact of
      Variation of a Single Transcription Factor on Differential Gene Expression in
      4NQO, Fermentable, and Nonfermentable Carbon Sources.
AB  - Cellular metabolism can change the potency of a chemical's tumorigenicity. 4
      nitroquinoline-1-oxide (4NQO) is a tumorigenic drug widely used on animal models
      for cancer research. Polymorphisms of the transcription factor Yrr1 confer
      different levels of resistance to 4NQO in Saccharomyces cerevisiae To study how
      different Yrr1 alleles regulate gene expression leading to resistance,
      transcriptomes of three isogenic Scerevisiae strains carrying different Yrr1
      alleles were profiled via RNA sequencing (RNA-Seq) and chromatin
      immunoprecipitation coupled with sequencing (ChIP-Seq) in the presence and
      absence of 4NQO. In response to 4NQO, all alleles of Yrr1 drove the expression of
      SNQ2 (a multidrug transporter), which was highest in the presence of 4NQO
      resistance-conferring alleles, and overexpression of SNQ2 alone was sufficient to
      overcome 4NQO-sensitive growth. Using shape metrics to refine the ChIP-Seq peaks,
      Yrr1 strongly associated with three loci including SNQ2 In addition to a known
      Yrr1 target SNG1, Yrr1 also bound upstream of RPL35B; however, overexpression of
      these genes did not confer 4NQO resistance. RNA-Seq data also implicated
      nucleotide synthesis pathways including the de novo purine pathway, and the
      ribonuclease reductase pathways were downregulated in response to 4NQO.
      Conversion of a 4NQO-sensitive allele to a 4NQO-resistant allele by a single
      point mutation mimicked the 4NQO-resistant allele in phenotype, and while the
      4NQO resistant allele increased the expression of the ADE genes in the de novo
      purine biosynthetic pathway, the mutant Yrr1 increased expression of ADE genes
      even in the absence of 4NQO. These same ADE genes were only increased in the wild
      type alleles in the presence of 4NQO, indicating that the point mutation
      activated Yrr1 to upregulate a pathway normally only activated in response to
      stress. The various Yrr1 alleles also influenced growth on different carbon
      sources by altering the function of the mitochondria. Hence, the complement to
      4NQO resistance was poor growth on nonfermentable carbon sources, which in turn
      varied depending on the allele of Yrr1 expressed in the isogenic yeast. The
      oxidation state of the yeast affected the 4NQO toxicity by altering the reactive
      oxygen species (ROS) generated by cellular metabolism. The integration of RNA-Seq
      and ChIP-Seq elucidated how Yrr1 regulates global gene transcription in response
      to 4NQO and how various Yrr1 alleles confer differential resistance to 4NQO. This
      study provides guidance for further investigation into how Yrr1 regulates
      cellular responses to 4NQO, as well as transcriptomic resources for further
      analysis of transcription factor variation on carbon source utilization.

PMID- 29208651
TI  - A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand
      Disease Type 3.
AB  - Von Willebrand Disease (VWD) type 3 is a serious and sometimes fatal hereditary
      bleeding disorder. In pigs, the disease has been known for decades, and affected
      animals are used as models for the human disease. Due to the recessive mode of
      inheritance of VWD type 3, severe bleeding is typically seen in homozygous
      individuals. We sequenced the complete porcine VWF (Von Willebrand Factor)
      complementary DNA (cDNA) and detected a tandem duplication of exons 17 and 18,
      causing a frameshift and a premature termination codon (p.Val814LeufsTer3) in the
      affected pig. Subsequent next generation sequencing on genomic DNA proved the
      existence of a 12.3-kb tandem duplication associated with VWD. This duplication
      putatively originates from porcine Short Interspersed Nuclear Elements (SINEs)
      located within VWF introns 16 and 18 with high identity. The premature
      termination truncates the VWF open reading frame by a large part, resulting in an
      almost entire loss of the mature peptide. It is therefore supposed to account for
      the severe VWD type 3. Our results further indicate the presence of strong,
      nonsense-mediated decay in VWF messenger RNA (mRNA) containing the duplication,
      which was supported by the almost complete absence of the complete VWF protein in
      immunohistochemistry analysis of the VWD-affected pig. In the past,
      differentiation of wild-type and heterozygous pigs in this VWD colony had to rely
      on clinical examinations and additional laboratory methods. The present study
      provides the basis to distinguish both genotypes by performing a rapid and simple
      genetic analysis.

PMID- 29208652
TI  - Is continuous electronic fetal monitoring useful for all women in labour?

PMID- 29208653
TI  - Twin Pregnancy With Gestational Diabetes Mellitus: A Double Whammy?

PMID- 29208655
TI  - Obstructive Sleep Apnea and Diabetes Independently Add to Cardiovascular Risk
      After Coronary Revascularization.

PMID- 29208654
TI  - Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular
      Events in Patients With Type 2 Diabetes.
AB  - OBJECTIVE: The goal of this study was to determine whether plasma levels of
      advanced glycation end products (AGE) and oxidation products (OP) predict the
      incidence of cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine,
      carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal
      hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide
      [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1)
      a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a
      nested case-control subgroup from the Action to Control Cardiovascular Risk in
      Diabetes (ACCORD) study (n = 271). RESULTS: Increased levels of several AGE and
      OP were associated with older age, decreased kidney function, previous CVD, and
      longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased
      risk of incident CVD events (n = 107) was associated with lower MetSO after
      adjusting for age, race/ethnicity, sex, prior CVD event, kidney function,
      treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28
      0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone
      hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01).
      In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by
      14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by
      18% and 15%, respectively; P = 0.04 for both); however, only the difference in
      MetSO remained significant after adjustment for prior CVD event (P = 0.002).
      CONCLUSIONS: Lower levels of MetSO and higher levels of select AGE are associated
      with increased incident CVD and may help account for the limited benefit of
      intensive glucose lowering in type 2 diabetes.

PMID- 29208656
TI  - PvdO is required for the oxidation of dihydropyoverdine as the last step of
      fluorophore formation in Pseudomonas fluorescens.
AB  - Pyoverdines are important siderophores that guarantee iron supply to important
      pathogenic and non-pathogenic pseudomonads in host habitats. A key characteristic
      of all pyoverdines is the fluorescent dihydroxyquinoline group that contributes
      two ligands to the iron complexes. Pyoverdines are derived from the non
      ribosomally synthesized peptide ferribactin, and their fluorophore is generated
      by periplasmic oxidation and cyclization reactions of d-tyrosine and l
      diaminobutyric acid. The formation of the fluorophore is known to be driven by
      the periplasmic tyrosinase PvdP. Here we report that the putative periplasmic
      oxidoreductase PvdO of Pseudomonas fluorescens A506 is required for the final
      oxidation of dihydropyoverdine to pyoverdine, which completes the fluorophore.
      The pvdO deletion mutant accumulates dihydropyoverdine, and this phenotype is
      fully complemented by recombinant PvdO. The autoxidation of dihydropyoverdine at
      alkaline pH and the presence of high copper concentrations can mask this
      phenotype. Mutagenesis of conserved residues with potential catalytic function
      identified Glu-260 as an essential residue whose mutation abolished function
      without affecting stability or transport. Glu-260 of PvdO is at the exact
      position of the active-site cysteine in the structurally related formylglycine
      generating enzyme. Evolution thus used the same protein fold for two distinct
      functionalities. As purified PvdO was inactive, additional factors are required
      for catalysis.

PMID- 29208657
TI  - Assembly of intermediates for rapid membrane fusion.
AB  - Membrane fusion is essential for intracellular protein sorting, cell growth,
      hormone secretion, and neurotransmission. Rapid membrane fusion requires
      tethering and Sec1-Munc18 (SM) function to catalyze R-, Qa-, Qb-, and Qc-SNARE
      complex assembly in trans, as well as SNARE engagement by the SNARE-binding
      chaperone Sec17/alphaSNAP. The hexameric vacuolar HOPS (homotypic fusion and
      vacuole protein sorting) complex in the yeast Saccharomyces cerevisiae tethers
      membranes through its affinities for the membrane Rab GTPase Ypt7. HOPS also has
      specific affinities for the vacuolar SNAREs and catalyzes SNARE complex assembly,
      but the order of their assembly into a 4-SNARE complex is unclear. We now report
      defined assembly intermediates on the path to membrane fusion. We found that a
      prefusion intermediate will assemble with HOPS and the R, Qa, and Qc SNAREs, and
      that this assembly undergoes rapid fusion upon addition of Qb and Sec17. HOPS
      tethered membranes and all four vacuolar SNAREs formed a complex that underwent
      an even more dramatic burst of fusion upon Sec17p addition. These findings
      provide initial insights into an ordered fusion pathway consisting of the
      following intermediates and events: 1) Rab- and HOPS-tethered membranes, 2) a
      HOPS:R:Qa:Qc trans-complex, 3) a HOPS:4-SNARE trans-complex, 4) an engagement
      with Sec17, and 5) the rapid lipid rearrangements during fusion. In conclusion,
      our results indicate that the R:Qa:Qc complex forms in the context of membrane,
      Ypt7, HOPS, and trans-SNARE assembly and serves as a functional intermediate for
      rapid fusion after addition of the Qb-SNARE and Sec17 proteins.

PMID- 29208658
TI  - Unbiased Approach to Counteract Upward Drift in Cerebrospinal Fluid Amyloid-beta
      1-42 Analysis Results.
AB  - BACKGROUND: Low cerebrospinal fluid (CSF) amyloid-beta 1-42 (Abeta 1-42)
      concentrations indicate amyloid plaque accumulation in the brain, a pathological
      hallmark of Alzheimer disease (AD). Innotest assay values of Abeta 1-42 have
      gradually increased over the past 2 decades, which might lead to
      misclassification of AD when a single cutpoint for abnormality is used. We
      propose an unbiased approach to statistically correct for drift. METHODS: We
      determined year-specific cutpoints with Gaussian mixture modeling, based on the
      cross-section of bimodal distributions of Abeta 1-42 concentrations in 4397
      memory clinic patients. This allowed us to realign year-specific cutpoints as an
      unbiased method to remove drift from the data. Sensitivity and specificity to
      detect AD dementia were compared between corrected and uncorrected values.
      RESULTS: Abeta 1-42 values increased 22 pg/mL annually, and this could not be
      explained by changes in cohort composition. Our approach removed time
      dependencies [beta (SE) = 0.07 (0.59); P = 0.91]. Statistically correcting for
      drift improved the sensitivity to detect AD dementia to 0.90 (95% CI, 0.89-0.92)
      from at least 0.66 (95% CI, 0.64-0.69) based on uncorrected data. Specificity
      became lower (0.69; 95% CI, 0.67-0.70) vs at most 0.80 (95% CI, 0.79-0.82) for
      uncorrected data. CONCLUSIONS: This approach may also be useful to standardize
      Abeta 1-42 CSF concentrations across different centers and/or platforms, and to
      optimize use of CSF biomarker data collected over a long period.

PMID- 29208659
TI  - Rapid Diagnosis of Tick-Borne Illnesses by Use of One-Step Isothermal Nucleic
      Acid Amplification and Bio-Optical Sensor Detection.
AB  - BACKGROUND: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS)
      are the most common tick-borne illnesses in South Korea. Early differentiation of
      SFTS from scrub typhus in emergency departments is essential but difficult
      because of their overlapping epidemiology, shared risk factors, and similar
      clinical manifestations. METHODS: We compared the diagnostic performance of one
      step isothermal nucleic acid amplification with bio-optical sensor detection
      (iNAD) under isothermal conditions, which is rapid (20-30 min), with that of real
      time PCR, in patients with a confirmed tick-borne illness. Fifteen patients with
      confirmed SFTS who provided a total of 15 initial blood samples and 5 follow-up
      blood samples, and 21 patients with confirmed scrub typhus, were evaluated.
      RESULTS: The clinical sensitivity of iNAD (100%; 95% CI, 83-100) for SFTS was
      significantly higher than that of real-time PCR (75%; 95% CI, 51-91; P = 0.047),
      while its clinical specificity (86%; 95% CI, 65-97) was similar to that of real
      time PCR (95%; 95% CI, 77-99; P = 0.61). The clinical sensitivity of iNAD for
      scrub typhus (100%; 95% CI, 81-100) was significantly higher than that of real
      time PCR for scrub typhus (67%; 95% CI, 43-85; P = 0.009), while its clinical
      specificity (90%; 95% CI, 67-98) was similar to that of real-time PCR (95%; 95%
      CI, 73-100; P > 0.99). CONCLUSIONS: iNAD is a valuable, rapid method of detecting
      SFTS virus and Orientia tsutsugamushi with high clinical sensitivity and
      specificity.

PMID- 29208660
TI  - Dynamics of Clinically Important Proteins: Measuring Turnover of Drug Targets and
      Biomarkers.

PMID- 29208661
TI  - Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with
      Cushing Syndrome.
AB  - BACKGROUND: Diagnosis of Cushing syndrome requires a multistep process that
      includes verification of hypercortisolism followed by identification of the cause
      of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic,
      and adrenal subtypes of Cushing syndrome were characterized by distinct plasma
      steroid profiles that might assist diagnosis. METHODS: In this retrospective
      cross-sectional study, mass spectrometric measurements of a panel of 15 plasma
      steroids were applied to 222 patient samples tested for Cushing syndrome. Disease
      was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome,
      12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease.
      Another 277 age- and sex-matched hypertensive and normotensive volunteers were
      included for comparison. RESULTS: Compared with patients without disease, the
      largest increases in plasma steroids among patients with Cushing syndrome were
      observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11
      deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients
      with ectopic disease showed the most prominent increases, but there was
      considerable variation for other steroids according to subtype. Patients with
      adrenal disease had the lowest concentrations of androgens, whereas those with
      ectopic and pituitary disease showed the lowest concentrations of aldosterone.
      Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10
      selected steroids, subjects with and without different Cushing syndrome subtypes
      could be discriminated nearly as closely as with the use of salivary and urinary
      free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin
      (9.5% vs 5.8% misclassification). CONCLUSIONS: Patients with different subtypes
      of Cushing syndrome show distinctive plasma steroid profiles that may offer a
      supplementary single-test alternative for screening purposes.

PMID- 29208662
TI  - Antenatal corticosteroids in impending preterm deliveries before 25 weeks'
      gestation.
AB  - Antenatal corticosteroid (ANC) use before 25 weeks' gestation is controversial.
      Our previous systematic review (eight observational studies, n=10 109) showed
      that ANC exposure was associated with significantly reduced mortality and severe
      intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL) in neonates
      born <25 weeks. We update our review by adding data (n=3334) from a recent study.
      We used Cochrane methodology and summarised the results using GRADE (The Grading
      of Recommendations Assessment, Development and Evaluation) guidelines. Nine high
      quality observational studies were included. Meta-analysis (random effects model)
      showed reduced mortality (n=13 443; OR=0.48 (95% CI 0.42 to 0.55) P<0.00001;
      level of evidence (LOE): moderate) and IVH or PVL (n=8418; OR=0.70 (95% CI 0.63
      to 0.79), P<0.00001; LOE: moderate) in neonates born <25 weeks exposed to ANC.
      There was no difference in necrotising enterocolitis (NEC) >=stage II (n=8737;
      OR=1.01 (95% CI 0.84 to 1.22), P=0.89; LOE: low); incidence of chronic lung
      disease (CLD) was higher (n=7983; OR=1.32 (95% CI 1.04 to 1.67), P=0.02; LOE:
      low) in ANC group. Composite outcomes of death/major morbidities (eg, severe IVH,
      NEC, CLD) were improved after ANC exposure.

PMID- 29208663
TI  - Haemodynamic effects of umbilical cord milking in premature sheep during the
      neonatal transition.
AB  - OBJECTIVE: Umbilical cord milking (UCM) at birth may benefit preterm infants, but
      the physiological effects of UCM are unknown. We compared the physiological
      effects of two UCM strategies with immediate umbilical cord clamping (UCC) and
      physiological-based cord clamping (PBCC) in preterm lambs. METHODS: At 126 days'
      gestational age, fetal lambs were exteriorised, intubated and instrumented to
      measure umbilical, pulmonary and cerebral blood flows and arterial pressures.
      Lambs received either (1) UCM without placental refill (UCMwoPR); (2) UCM with
      placental refill (UCMwPR); (3) PBCC, whereby ventilation commenced prior to UCC;
      or (4) immediate UCC. UCM involved eight milks along a 10 cm length of cord,
      followed by UCC. RESULTS: A net volume of blood was transferred into the lamb
      during UCMwPR (8.8 mL/kg, IQR 8-10, P=0.01) but not during UCMwoPR (0 mL/kg, IQR 
      2.8 to 1.7) or PBCC (1.1 mL/kg, IQR -1.3 to 4.3). UCM had no effect on pulmonary
      blood flow, but caused large fluctuations in mean carotid artery pressures (MBP)
      and blood flows (CABF). In UCMwoPR and UCMwPR lambs, MBP increased by 12%+/-1%
      and 8%+/-1% and CABF increased by 32%+/-2% and 15%+/-2%, respectively, with each
      milk. Cerebral oxygenation decreased the least in PBCC lambs (17%, IQR 13-26)
      compared with UCMwoPR (26%, IQR 23-25, P=0.03), UCMwPR (35%, IQR 27-44, P=0.02)
      and immediate UCC (34%, IQR 28-41, P=0.02) lambs. CONCLUSIONS: UCMwoPR failed to
      provide placental transfusion, and UCM strategies caused considerable
      haemodynamic disturbance. UCM does not provide the same physiological benefits of
      PBCC. Further review of UCM is warranted before adoption into routine clinical
      practice.

PMID- 29208664
TI  - Improving intrapartum care: can we use routinely available data to monitor the
      effects of our actions?

PMID- 29208665
TI  - Cognitive trajectories from infancy to early adulthood in the EPICure cohort:
      time to refocus research on how to break the 'natural limits' of brain
      plasticity.

PMID- 29208667
TI  - Etk Interaction with PFKFB4 Modulates Chemoresistance of Small-cell Lung Cancer
      by Regulating Autophagy.
AB  - Purpose: Epithelial and endothelial tyrosine kinase (Etk), also known as bone
      marrow X kinase (Bmx), was found to be critical in modulating the chemoresistance
      of small-cell lung cancer (SCLC) in our preliminary study. However, the molecular
      mechanisms of Etk in SCLC chemoresistance remain poorly understood.Experimental
      Design: We determined correlation of Etk with autophagy in SCLC. And direct
      inhibition of autophagy was performed to validate its effect on chemoresistance.
      Coimmunoprecipitation (co-IP) and GST-pull down experiments were conducted to
      verify the interaction of Etk and PFKFB4, after a microarray analysis. In vitro
      and in vivo gain or loss-of-function analyses and evaluation of PFKFB4 expression
      in SCLC specimens, were done to validate its role in chemoresistance. Ibrutinib
      was administrated in SCLC cells to verify its synergistic anti-tumor effect with
      chemotherapy using preclinical models including a PDX model.Results:
      Downregulation of Etk suppressed autophagy in chemoresistant SCLC cells, and
      direct inhibition of autophagy sensitized cells to chemotherapy. PFKFB4 (6
      phosphofructo-2-kinase/fructose-2,6-biphosphatase 4) was identified as a
      downstream target of Etk and an Etk-interacting protein, which promoted
      chemoresistance in SCLC and was associated with poor therapeutic response and
      prognosis. Furthermore, ibrutinib was found to exhibit a synergistic anti-tumor
      effect with chemotherapy in targeting Etk.Conclusions: Our results demonstrated
      for the first time that Etk interacts with PFKFB4 to promote SCLC chemoresistance
      through regulation of autophagy. Aberrant Etk and PFKFB4 can be predictive
      factors for the chemotherapy response as well as potential therapeutic targets in
      SCLC. Clin Cancer Res; 24(4); 950-62. (c)2017 AACR.

PMID- 29208666
TI  - Epidemiology of UK neonatal infections: the neonIN infection surveillance
      network.
AB  - OBJECTIVE: To describe the epidemiology of neonatal infection over the past
      decade in UK neonatal units. DESIGN: Retrospective analysis of prospectively
      collected infection surveillance network data from 2005 to 2014. SETTING: 30
      neonatal units in the UK. PATIENTS: Newborns on participating neonatal units who
      had a positive blood, cerebrospinal fluid or urine culture and were treated with
      at least 5 days of appropriate antibiotics. RESULTS: 2171 episodes of neonatal
      infection in 1922 infants were recorded. The incidence of infection was 6.1/1000
      live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if
      coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of
      infection showed a statistically significant reduction over time with reductions
      in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The
      majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth),
      and infection was more common in premature (<37 weeks gestation) and low birth
      weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified
      pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS,
      while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes
      of LOS. CONCLUSIONS: This paper describes the epidemiology of neonatal infection
      in the UK over the past decade. These data enable benchmarking of practice and
      inform areas of future research and guideline development. The results support
      the hypothesis that the introduction of infection prevention care bundles and
      antibiotic stewardship programmes in the UK has reduced the burden of LOS.

PMID- 29208668
TI  - A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in
      Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or
      FOLFIRI/Cetuximab.
AB  - Purpose: Vitamin D exerts its inhibitory influence on colon cancer growth by
      inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes
      involved in vitamin D transport, metabolism, and signaling are associated with
      outcome in metastatic colorectal cancer (mCRC) patients treated with first-line
      FOLFIRI and bevacizumab.Experimental Design: 522 mCRC patients enrolled in the
      FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with
      FOLFIRI/bevacizumab were included in this study. 278 patients receiving FOLFIRI
      and cetuximab (FIRE-3) served as a control cohort. Six SNPs in 6 genes (GC,
      CYP24A1, CYP27B1, VDR, DKK1, CST5) were analyzed.Results: In the discovery
      cohort, AA carriers of the GC rs4588 SNP encoding for the vitamin D-binding
      protein, and treated with FOLFIRI/bevacizumab had a shorter overall survival (OS)
      than those harboring any C allele (15.9 vs. 25.1 months) in both univariable (P =
      0.001) and multivariable analyses (P = 0.047). This association was confirmed in
      the validation cohort in multivariable analysis (OS 18.1 vs. 26.2 months, HR,
      1.83; P = 0.037). Interestingly, AA carriers in the control set exhibited a
      longer OS (48.0 vs. 25.2 months, HR, 0.50; P = 0.021). This association was
      further confirmed in a second validation cohort comprising refractory mCRC
      patients treated with cetuximab +/- irinotecan (PFS 8.7 vs. 3.7 months) in
      univariable (P = 0.033) and multivariable analyses (P = 0.046).Conclusions:GC
      rs4588 SNP might serve as a predictive marker in mCRC patients treated with
      FOLFIRI/bevacizumab or FOLFIRI/cetuximab. Whereas AA carriers derive a survival
      benefit with FOLFIRI/cetuximab, treatment with FOLFIRI/bevacizumab is associated
      with a worse outcome. Clin Cancer Res; 24(4); 784-93. (c)2017 AACR.

PMID- 29208670
TI  - Inhibition of ID1-BMPR2 Intrinsic Signaling Sensitizes Glioma Stem Cells to
      Differentiation Therapy.
AB  - Purpose: Normal stem cells tightly control self-renewal and differentiation
      during development, but their neoplastic counterparts, cancer stem cells (CSCs),
      sustain tumorigenicity both through aberrant activation of stemness and evasion
      of differentiation. Although regulation of CSC stemness has been extensively
      studied, the molecular mechanisms suppressing differentiation remain
      unclear.Experimental Design: We performed in silico screening and in vitro
      validation studies through Western blotting, qRT-PCR for treatment of WNT and SHH
      signaling inhibitors, and BMP signaling inducer with control and ID1
      overexpressing cells. We also performed in vivo drug treatment assays with Balb/c
      nude mice.Results: Inhibitor of differentiation 1 (ID1) abrogated differentiation
      signals from bone morphogenetic protein receptor (BMPR) signaling in glioblastoma
      stem cells (GSCs) to promote self-renewal. ID1 inhibited BMPR2 expression through
      miRNAs, miR-17 and miR-20a, which are transcriptional targets of MYC. ID1
      increases MYC expression by activating WNT and SHH signaling. Combined
      pharmacologic blockade of WNT and SHH signaling with BMP treatment significantly
      suppressed GSC self-renewal and extended survival of tumor-bearing
      mice.Conclusions: Collectively, our results suggested that ID1 simultaneously
      regulates stemness through WNT and SHH signaling and differentiation through BMPR
      mediated differentiation signaling in GSCs, informing a novel therapeutic
      strategy of combinatorial targeting of stemness and differentiation. Clin Cancer
      Res; 24(2); 383-94. (c)2017 AACR.

PMID- 29208669
TI  - Vimentin Is Required for Lung Adenocarcinoma Metastasis via Heterotypic Tumor
      Cell-Cancer-Associated Fibroblast Interactions during Collective Invasion.
AB  - Purpose: Vimentin is an epithelial-to-mesenchymal transition (EMT) biomarker and
      intermediate filament protein that functions during cell migration to maintain
      structure and motility. Despite the abundance of clinical data linking vimentin
      to poor patient outcome, it is unclear if vimentin is required for metastasis or
      is a correlative biomarker. We developed a novel genetically engineered mouse
      model (GEMM) to probe vimentin in lung adenocarcinoma metastasis.Experimental
      Design: We used the LSL-KrasG12D/Lkb1fl/fl/Vim-/- model (KLV-/-), which
      incorporates a whole-body knockout of vimentin and is derived from the Cre
      dependent LSL-KrasG12D/Lkb1fl/fl model (KLV+/+). We compared the metastatic
      phenotypes of the GEMMs and analyzed primary tumors from the KLV models and lung
      adenocarcinoma patients to assess vimentin expression and function.Results:
      Characterization of KLV+/+ and KLV-/- mice shows that although vimentin is not
      required for primary lung tumor growth, vimentin is required for metastasis, and
      vimentin loss generates lower grade primary tumors. Interestingly, in the KLV+/+
      mice, vimentin was not expressed in tumor cells but in cancer-associated
      fibroblasts (CAFs) surrounding collective invasion packs (CIPs) of epithelial
      tumor cells, with significantly less CIPs in KLV-/- mice. CIPs correlate with
      tumor grade and are vimentin-negative and E-cadherin-positive, indicating a lack
      of cancer cell EMT. A similar heterotypic staining pattern was observed in human
      lung adenocarcinoma samples. In vitro studies show that vimentin is required for
      CAF motility to lead tumor cell invasion, supporting a vimentin-dependent model
      of collective invasion.Conclusions: These data show that vimentin is required for
      lung adenocarcinoma metastasis by maintaining heterotypic tumor cell-CAF
      interactions during collective invasion. Clin Cancer Res; 24(2); 420-32. (c)2017
      AACR.

PMID- 29208671
TI  - CXCR4 Is a Potential Target for Diagnostic PET/CT Imaging in Barrett's Dysplasia
      and Esophageal Adenocarcinoma.
AB  - Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading
      to esophageal adenocarcinoma. Considerable evidence supports a major role for
      chronic inflammation and diverse chemokine pathways in the development of
      Barrett's esophagus and esophageal adenocarcinoma.Experimental Design: Here we
      utilized an IL1beta transgenic mouse model of Barrett's esophagus and esophageal
      adenocarcinoma and human patient imaging to analyze the importance of CXCR4
      expressing cells during esophageal carcinogenesis.Results: IL1beta overexpression
      induces chronic esophageal inflammation and recapitulates the progression to
      Barrett's esophagus and esophageal adenocarcinoma. CXCR4 expression is increased
      in both epithelial and immune cells during disease progression in pL2-IL1beta
      mice and also elevated in esophageal adenocarcinoma patient biopsy samples.
      Specific recruitment of CXCR4-positive (CXCR4+) immune cells correlated with
      dysplasia progression, suggesting that this immune population may be a key
      contributor to esophageal carcinogenesis. Similarly, with progression to
      dysplasia, there were increased numbers of CXCR4+ columnar epithelial cells at
      the squamocolumnar junction (SCJ). These findings were supported by stronger
      CXCR4-related signal intensity in ex vivo fluorescence imaging and
      autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging
      studies in patients with esophageal cancer demonstrate the potential utility of
      CXCR4 imaging for the diagnosis and staging of esophageal cancer.Conclusion: In
      conclusion, the recruitment of CXCR4+ immune cells and expansion of CXCR4+
      epithelial cells in esophageal dysplasia and cancer highlight the potential of
      CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor
      microenvironment in esophageal adenocarcinoma. Clin Cancer Res; 24(5); 1048-61.
      (c)2017 AACR.

PMID- 29208672
TI  - CD271 Confers an Invasive and Metastatic Phenotype of Head and Neck Squamous Cell
      Carcinoma through the Upregulation of Slug.
AB  - Purpose: Head and neck squamous cell carcinoma (HNSCC) is comprised of
      heterogeneous populations of cells, and CD271 (NGFR; p75NTR) has been associated
      with a tumor-initiating cell subpopulation. This study assessed the role of CD271
      in modulating metastatic behavior in HNSCC.Experimental Design: CD271 was
      overexpressed in murine and human oral squamous cell carcinoma cells to assess
      the impact of CD271 activation on the invasive and metastatic phenotype of these
      cells, using in vitro and orthotopic in vivo modeling. Treatment with human nerve
      growth factor (NGF) to activate CD271, as well as shRNA knockdown of the CD271
      upregulated Snai2 expression, was used to assess the mechanism of the CD271
      induced invasive phenotype. Relevance of CD271 expression in human HNSCC was
      evaluated in patient-derived xenografts (PDX) and primary human oral cancers,
      annotated with clinical behavior characteristics and survival data.Results:
      Forced expression of CD271 resulted in a more invasive and metastatic phenotype.
      Slug, an epithelial-to-mesenchymal transition (EMT)-related transcription factor,
      encoded by Snai2, was highly expressed in MOC2-CD271 and HSC3-CD271, compared
      with respective parental cells. CD271 activation by NGF conferred enhanced
      invasiveness in CD271-overexpressing cells, which was abrogated by Snai2
      knockdown. In PDXs and primary human HNSCC, CD271 expression correlated with
      higher Snai2 expression, greater nodal metastasis, and shorter disease-free
      survival.Conclusions: Activation of CD271 results in upregulation of Snai2/Slug,
      which, in turn, results in a more invasive phenotype and an enhanced capacity for
      metastasis to regional lymph nodes. These findings point to CD271 as a promising,
      therapeutic target for oral cancer metastasis. Clin Cancer Res; 24(3); 674-83.
      (c)2017 AACR.

PMID- 29208673
TI  - Biomarkers of Primary Resistance to Trastuzumab in HER2-Positive Metastatic
      Gastric Cancer Patients: the AMNESIA Case-Control Study.
AB  - Purpose: Refining the selection of HER2-positive metastatic gastric cancer
      patient candidates for trastuzumab is a challenge of precision oncology.
      Preclinical studies have suggested several genomic mechanisms of primary
      resistance, leading to activation of tyrosine kinase receptors other than HER2 or
      downstream signaling pathways.Experimental Design: We carried out this
      multicenter, prospective, case-control study to demonstrate the negative
      predictive impact of a panel of candidate genomic alterations (AMNESIA panel),
      including EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications.
      Hypothesizing a prevalence of candidate alterations of 30% and 0% in resistant
      and sensitive HER2-positive patients, respectively, 20 patients per group were
      needed.Results: AMNESIA panel alterations were significantly more frequent in
      resistant (11 of 20, 55%) as compared with sensitive (0% of 17) patients (P <
      0.001), and in HER2 IHC 2+ (7 of 13, 53.8%) than 3+ (4 of 24, 16.7%) tumors (P =
      0.028). Patients with tumors bearing no candidate alterations had a significantly
      longer median progression-free [5.2 vs. 2.6 months; HR, 0.34; 95% confidence
      interval (CI), 0.07-0.48; P = 0.001] and overall survival (16.1 vs. 7.6 months;
      HR, 0.38; 95% CI, 0.09-0.75; P = 0.015). The predictive accuracy of the AMNESIA
      panel and HER2 IHC was 76% and 65%, respectively. The predictive accuracy of the
      combined evaluation of the AMNESIA panel and HER2 IHC was 84%.Conclusions: Our
      panel of candidate genomic alterations may be clinically useful to predict
      primary resistance to trastuzumab in patients with HER2-positive metastatic
      gastric cancer and should be further validated with the aim of molecularly
      stratifying HER2-addicted cancers for the development of novel treatment
      strategies. Clin Cancer Res; 24(5); 1082-9. (c)2017 AACR.

PMID- 29208674
TI  - Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2
      Ca2+ channels.
AB  - Voltage-gated Cav2.1 (P/Q-type) Ca2+ channels undergo Ca2+-dependent inactivation
      (CDI) and facilitation (CDF), both of which contribute to short-term synaptic
      plasticity. Both CDI and CDF are mediated by calmodulin (CaM) binding to sites in
      the C-terminal domain of the Cav2.1 alpha1 subunit, most notably to a consensus
      CaM-binding IQ-like (IQ) domain. Closely related Cav2.2 (N-type) channels display
      CDI but not CDF, despite overall conservation of the IQ and additional sites (pre
      IQ, EF-hand-like [EF] domain, and CaM-binding domain) that regulate CDF of
      Cav2.1. Here we investigate the molecular determinants that prevent Cav2.2
      channels from undergoing CDF. Although alternative splicing of C-terminal exons
      regulates CDF of Cav2.1, the splicing of analogous exons in Cav2.2 does not
      reveal CDF. Transfer of sequences encoding the Cav2.1 EF, pre-IQ, and IQ together
      (EF-pre-IQ-IQ), but not individually, are sufficient to support CDF in chimeric
      Cav2.2 channels; Cav2.1 chimeras containing the corresponding domains of Cav2.2,
      either alone or together, fail to undergo CDF. In contrast to the weak binding of
      CaM to just the pre-IQ and IQ of Cav2.2, CaM binds to the EF-pre-IQ-IQ of Cav2.2
      as well as to the corresponding domains of Cav2.1. Therefore, the lack of CDF in
      Cav2.2 likely arises from an inability of its EF-pre-IQ-IQ to transduce the
      effects of CaM rather than weak binding to CaM per se. Our results reveal a
      functional divergence in the CDF regulatory domains of Cav2 channels, which may
      help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic
      transmission.

PMID- 29208675
TI  - Why attempt en bloc resection of non-pedunculated colorectal adenomas? A
      systematic review of the prevalence of superficial submucosal invasive cancer
      after endoscopic submucosal dissection.
AB  - OBJECTIVE: Endoscopic submucosal dissection (ESD) aims to achieve en bloc
      resection of non-pedunculated colorectal adenomas which might be indicated in
      cases with superficial submucosal invasive cancers (SMIC), but the procedure is
      time consuming and complex. The prevalence of such cancers is not known but may
      determine the clinical necessity for ESD as opposed to the commonly used
      piecemeal mucosal resection (endoscopic mucosal resection) of colorectal
      adenomas. The main aim was to assess the prevalence of SMIC SM1 (ie, invasion
      <=1000 um or less than one-third of the submucosa) on colorectal lesions removed
      by ESD. DESIGN: A literature review was conducted using electronic databases (up
      to March 2017) for colorectal ESD series reporting the histology of the dissected
      lesions. RESULTS: 51 studies with data on 11 260 colorectal dissected lesions
      were included. Most resected lesions (82.2%; 95% CI 78.8% to 85.3%) were adenomas
      (low- and high-grade dysplasia, 26.8% and 55.4%, respectively). Overall, 15.7%
      were submucosal cancers, but only slightly more than half (8.0%; 95% CI 6.1% to
      10.3%) had an infiltration depth of <=1000 um, providing a number needed to treat
      (NNT) to avoid one surgery of 12.5. Estimating an oncologically curative (R0;
      G1/2; L0/V0) resection rate of 75.3% (95% CI 52.2% to 89.4%) for malignant
      lesions, the prevalence of curative resection lowered to 6% (95% CI 4.2% to 7.2%)
      with an NNT of 16.7. CONCLUSION: The low prevalence of SMIC SM1 in lesions
      selected for ESD as well as the even lower rate of curative resection limits the
      clinical applicability of endoscopic en bloc resection. This calls for caution
      over an indiscriminate use of this technique in the resection of colorectal
      neoplasia.

PMID- 29208676
TI  - Vonoprazan, aspirin and NSAIDs: new era in acid inhibition and gastroprotection.

PMID- 29208677
TI  - Intestinal organoid culture model is a valuable system to study epithelial
      barrier function in IBD.

PMID- 29208678
TI  - MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of
      Endothelial Autophagy.
AB  - RATIONALE: The interaction of circulating cells within the vascular wall is a
      critical event in chronic inflammatory processes, such as atherosclerosis, but
      the control of the vascular inflammatory state is still largely unclear.
      OBJECTIVE: This study was undertaken to characterize the function of the
      endothelial-enriched microRNA miR-100 during vascular inflammation and
      atherogenesis. METHODS AND RESULTS: Based on a transcriptome analysis of
      endothelial cells after miR-100 overexpression, we identified miR-100 as a potent
      suppressor of endothelial adhesion molecule expression, resulting in attenuated
      leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry
      and intravital imaging. Mechanistically, miR-100 directly repressed several
      components of mammalian target of rapamycin complex 1-signaling, including
      mammalian target of rapamycin and raptor, which resulted in a stimulation of
      endothelial autophagy and attenuated nuclear factor kappaB signaling in vitro and
      in vivo. In a low-density lipoprotein receptor-deficient atherosclerotic mouse
      model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion
      formation and a higher macrophage content of the plaque, whereas a systemic miR
      100 replacement therapy had protective effects and attenuated atherogenesis,
      resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100
      expression in >70 samples obtained during carotid endarterectomy revealed that
      local miR-100 expression was inversely correlated with inflammatory cell content
      in patients. CONCLUSIONS: In summary, we describe an anti-inflammatory function
      of miR-100 in the vascular response to injury and inflammation and identify an
      important novel modulator of mammalian target of rapamycin signaling and
      autophagy in the vascular system. Our findings of miR-100 as a potential
      protective anti-athero-miR suggest that the therapeutic replacement of this
      microRNA could be a potential strategy for the treatment of chronic inflammatory
      diseases, such as atherosclerosis, in the future.

PMID- 29208679
TI  - TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation
      Myocardial Infarction on the Recovery of Global and Regional Left Ventricular
      Function: Final 2-Year Analysis.
AB  - RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the
      first cell therapy trial sufficiently powered to determine if timing of cell
      delivery after ST-segment-elevation myocardial infarction affects recovery of
      left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and
      cardiac magnetic resonance imaging results and their modification by
      microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double
      blind, placebo-controlled trial comparing 150 million bone marrow mononuclear
      cells versus placebo in 120 patients with anterior ST-segment-elevation
      myocardial infarctions resulting in LV dysfunction. Primary end points included
      changes in global (LV ejection fraction) and regional (infarct and border zone)
      function. Secondary end points included changes in LV volumes, infarct size, and
      major adverse cardiac events. Here, we analyzed the continued trajectory of these
      measures out to 2 years and the influence of microvascular obstruction present at
      baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was
      similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%)
      with no difference in regional LV function. Infarct size and LV mass decreased
      >=30% in each group at 6 months and declined gradually to 2 years. LV volumes
      increased ~10% at 6 months and remained stable to 2 years. Microvascular
      obstruction was present in 48 patients at baseline and was associated with
      significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV
      remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus
      6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance
      imaging analyses of patients with large anterior ST-segment-elevation myocardial
      infarctions, bone marrow mononuclear cells administration did not improve
      recovery of LV function over 2 years. Microvascular obstruction was associated
      with reduced recovery of LV function, greater adverse LV remodeling, and more
      device implantations. The use of cardiac magnetic resonance imaging leads to
      greater dropout of patients over time because of device implantation in patients
      with more severe LV dysfunction resulting in overestimation of clinical stability
      of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00684021.

PMID- 29208681
TI  - HemITAM: A single tyrosine motif that packs a punch.
AB  - Innate immune cells sense danger through a plethora of germline-encoded receptors
      that recognize pathogen-associated molecular patterns (PAMPs) or cellular
      molecules that are exposed only by stressed, infected, malignant, or dead cells.
      Many of these danger-sensing receptors belong to the C-type lectin-like
      superfamily (CLSF) and therefore are called C-type lectin-like receptors (CTLRs).
      Certain activating CTLRs, namely, CLEC-2, Dectin-1, DNGR-1, NKp80, and NKp65,
      which are encoded by genes that are clustered together in a subregion of the
      mammalian natural killer gene complex (NKC), use a single copy tyrosine signaling
      module termed the hemi-immunoreceptor tyrosine-based activation motif (hemITAM).
      These hemITAM-bearing CTLRs are present on myeloid cells and innate lymphocytes
      and stimulate various functions, such as phagocytosis, cytokine production, and
      cytotoxicity. Proximal signaling mechanisms involve the tyrosine phosphorylation
      of the hemITAM and the subsequent activation of the kinase Syk. Signaling and Syk
      recruitment by the hemITAM appear to be tuned by variable amino acids within or
      near the hemITAM, which give rise to differences in downstream signaling events
      and diverging functional outcomes among hemITAM-bearing receptors.

PMID- 29208680
TI  - Subtle modifications to oxytocin produce ligands that retain potency and improved
      selectivity across species.
AB  - Oxytocin and vasopressin mediate various physiological functions that are
      important for osmoregulation, reproduction, cardiovascular function, social
      behavior, memory, and learning through four G protein-coupled receptors that are
      also implicated in high-profile disorders. Targeting these receptors is
      challenging because of the difficulty in obtaining ligands that retain
      selectivity across rodents and humans for translational studies. We identified a
      selective and more stable oxytocin receptor (OTR) agonist by subtly modifying the
      pharmacophore framework of human oxytocin and vasopressin. [Se-Se]-oxytocin-OH
      displayed similar potency to oxytocin but improved selectivity for OTR, an effect
      that was retained in mice. Centrally infused [Se-Se]-oxytocin-OH potently
      reversed social fear in mice, confirming that this action was mediated by OTR and
      not by V1a or V1b vasopressin receptors. In addition, [Se-Se]-oxytocin-OH
      produced a more regular contraction pattern than did oxytocin in a preclinical
      labor induction and augmentation model using myometrial strips from cesarean
      sections. [Se-Se]-oxytocin-OH had no activity in human cardiomyocytes, indicating
      a potentially improved safety profile and therapeutic window compared to those of
      clinically used oxytocin. In conclusion, [Se-Se]-oxytocin-OH is a novel probe for
      validating OTR as a therapeutic target in various biological systems and is a
      promising new lead for therapeutic development. Our medicinal chemistry approach
      may also be applicable to other peptidergic signaling systems with similar
      selectivity issues.

PMID- 29208682
TI  - The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by
      activating the transcriptional coactivators YAP and TAZ.
AB  - Malignant tumors reprogram cellular metabolism to support cancer cell
      proliferation and survival. Although most cancers depend on a high rate of
      aerobic glycolysis, many cancer cells also display addiction to glutamine.
      Glutamine transporters and glutaminase activity are critical for glutamine
      metabolism in tumor cells. We found that the receptor tyrosine kinase EphA2
      activated the TEAD family transcriptional coactivators YAP and TAZ (YAP/TAZ),
      likely in a ligand-independent manner, to promote glutamine metabolism in cells
      and mouse models of HER2-positive breast cancer. Overexpression of EphA2 induced
      the nuclear accumulation of YAP and TAZ and increased the expression of YAP/TAZ
      target genes. Inhibition of the GTPase Rho or the kinase ROCK abolished EphA2
      dependent YAP/TAZ nuclear localization. Silencing YAP or TAZ substantially
      reduced the amount of intracellular glutamate through decreased expression of
      SLC1A5 and GLS, respectively, genes that encode proteins that promote glutamine
      uptake and metabolism. The regulatory DNA elements of both SLC1A5 and GLS contain
      TEAD binding sites and were bound by TEAD4 in an EphA2-dependent manner. In
      patient breast cancer tissues, EphA2 expression positively correlated with that
      of YAP and TAZ, as well as that of GLS and SLC1A5 Although high expression of
      EphA2 predicted enhanced metastatic potential and poor patient survival, it also
      rendered HER2-positive breast cancer cells more sensitive to glutaminase
      inhibition. The findings define a previously unknown mechanism of EphA2-mediated
      glutaminolysis through YAP/TAZ activation in HER2-positive breast cancer and
      identify potential therapeutic targets in patients.

PMID- 29208683
TI  - IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through
      transcriptional networks.
AB  - Focal adhesion kinase (FAK) mediates tumor cell-intrinsic behaviors that promote
      tumor growth and metastasis. We previously showed that FAK also induces the
      expression of inflammatory genes that inhibit antitumor immunity in the
      microenvironment. We identified a crucial, previously unknown role for the dual
      function cytokine interleukin-33 (IL-33) in FAK-dependent immune evasion. In
      murine squamous cell carcinoma (SCC) cells, specifically nuclear FAK enhanced the
      expression of the genes encoding IL-33, the chemokine CCL5, and the soluble,
      secreted form of the IL-33 receptor, called soluble ST2 (sST2). The abundance of
      IL-33 and CCL5 was increased in FAK-positive SCC cells but not in normal
      keratinocytes. IL-33 associated with FAK in the nucleus, and the FAK-IL-33
      complex interacted with a network of chromatin modifiers and transcriptional
      regulators, including TAF9, WDR82, and BRD4, which promote the activity of
      nuclear factor kappaB (NF-kappaB) and its induction of genes encoding chemokines,
      including CCL5. We did not detect secretion of IL-33 from FAK-positive SCC cells;
      thus, we propose that the increased production and secretion of sST2 likely
      sequesters IL-33 secreted by other cell types within the tumor environment, thus
      blocking its stimulatory effects on infiltrating host immune cells. Depleting
      FAK, IL-33, or sST2 from SCC cells before implantation induced tumor regression
      in syngeneic mice, except when CD8+ T cells were co-depleted. Our data provide
      mechanistic insight into how FAK controls the tumor immune environment, namely,
      through a transcriptional regulatory network mediated by nuclear IL-33. Targeting
      this axis may boost antitumor immunity in patients.

PMID- 29208684
TI  - Central NPY-Y5 sub-receptor partially functions as a mediator of NPY-induced
      hypothermia and affords thermotolerance in heat-exposed fasted chicks.
AB  - Exposure of chicks to a high ambient temperature (HT) has previously been shown
      to increase neuropeptide Y (NPY) mRNA expression in the brain. Furthermore, it
      was found that NPY has anti-stress functions in heat-exposed fasted chicks. The
      aim of the study was to reveal the role of central administration of NPY on
      thermotolerance ability and the induction of heat-shock protein (HSP) and NPY sub
      receptors (NPYSRs) in fasted chicks with the contribution of plasma metabolite
      changes. Six- or seven-day-old chicks were centrally injected with 0 or 375 pmol
      of NPY and exposed to either HT (35 +/- 1 degrees C) or control thermoneutral
      temperature (CT: 30 +/- 1 degrees C) for 60 min while fasted. NPY reduced body
      temperature under both CT and HT NPY enhanced the brain mRNA expression of HSP-70
      and -90, as well as of NPYSRs-Y5, -Y6, and -Y7, but not -Y1, -Y2, and -Y4, under
      CT and HT A coinjection of an NPYSR-Y5 antagonist (CGP71683) and NPY (375 pmol)
      attenuated the NPY-induced hypothermia. Furthermore, central NPY decreased plasma
      glucose and triacylglycerol under CT and HT and kept plasma corticosterone and
      epinephrine lower under HT NPY increased plasma taurine and anserine
      concentrations. In conclusion, brain NPYSR-Y5 partially afforded protective
      thermotolerance in heat-exposed fasted chicks. The NPY-mediated reduction in
      plasma glucose and stress hormone levels and the increase in free amino acids in
      plasma further suggest that NPY might potentially play a role in minimizing heat
      stress in fasted chicks.

PMID- 29208685
TI  - Nonmuscle myosin 2 proteins encoded by Myh9, Myh10, and Myh14 are uniquely
      distributed in the tubular segments of murine kidney.
AB  - The diverse epithelial cell types of the kidneys are segregated into nephron
      segments and the collecting ducts in order to endow each tubular segment with
      unique functions. The rich diversity of the epithelial cell types is highlighted
      by the unique membrane channels and receptors expressed within each nephron
      segment. Our previous work identified a critical role for Myh9 and Myh10 in
      mammalian endocytosis. Here, we examined the expression patterns of Nonmuscle
      myosin 2 (NM2) heavy chains encoded by Myh9, Myh10, and Myh14 in mouse kidneys as
      these genes may confer unique nephron segment-specific membrane transport
      properties. Interestingly, we found that each segment of the renal tubules
      predominately expressed only two of the three NM2 isoforms, with isoform-specific
      subcellular localization, and different levels of expression within a nephron
      segment. Additionally, we identify Myh14 to be restricted to the intercalated
      cells and Myh10 to be restricted to the principal cells within the collecting
      ducts and connecting segments. We speculate that the distinct expression pattern
      of the NM2 proteins likely reflects the diversity of the intracellular
      trafficking machinery present within the different renal tubular epithelial
      segments.

PMID- 29208686
TI  - Effects of growth hormone administration on luteinizing hormone secretion in
      healthy older men and women.
AB  - The known interactions between the somatotropic and hypothalamic-pituitary
      gonadal (HPG) axes have not been well delineated in older individuals. Aging
      associated decline in insulin like growth factor-1 (IGF-1) levels has been
      proposed to play a role in reproductive senescence in animals. However, the
      effects of GH on LH secretion are unknown in older individuals. Our objective was
      to determine whether GH modulates LH secretion or levels of sex steroids (SS) in
      healthy older (ages 65-88 years) men (n = 24) and women (n = 24) with low-normal
      plasma IGF-1 levels. In a double-masked, placebo-controlled (n = 24), randomized
      study, we evaluated the effects of GH (n = 24, 20 MUg/kg sc 3*/week) for 26 weeks
      on nocturnal LH secretory dynamics [(8 pm to 8 am, Q20) min sampling and analyzed
      by multiparameter deconvolution algorithm]. Indices of LH secretion [frequency,
      mass per burst, pulsatile production rate, and approximate entropy (ApEn)] and
      fasting serum IGF-1, SHBG, and SS (TT, fT, or E2) were measured. At baseline, all
      indices of LH secretion (frequency, mass per burst, pulsatile production rate)
      were inversely (P < 0.05) related to IGF-1, but not to mean nocturnal serum GH
      concentrations. GH administration for 26 weeks increased serum IGF-1, but exerted
      no significant effects on LH secretory dynamics, or concentrations of SSs (TT,
      fT, or E2) or SHBG in older women or men. These data suggest that GH-mediated
      increases in IGF-1 do not modulate the HPG axis in older individuals.

PMID- 29208688
TI  - The impact of acute bouts of interval and continuous walking on energy-intake and
      appetite regulation in subjects with type 2 diabetes.
AB  - In healthy subjects, it has been suggested that exercise may acutely suppress
      energy-intake and appetite, with peak intensity being an important determinant
      for this effect. In subjects with type 2 diabetes (T2D), the effect of exercise
      on appetite-related variables is, however, virtually unknown. We aimed to assess
      the effects of two exercise interventions, differing with regards to peak
      intensity, on energy-intake, satiety and appetite-related hormones in subjects
      with T2D. Thirteen subjects with T2D completed three 60-min interventions with
      continuous measurement of oxygen consumption in a randomized and counterbalanced
      order: (1) Control, (2) Continuous walking (CW; intended 73% of VO2peak), (3)
      Interval-walking (IW; repeated cycles of 3 min slow [54% of VO2peak] and 3 min
      fast walking [89% of VO2peak]). Forty-five minutes after completion of the
      intervention, a 3-h liquid mixed meal tolerance test (MMTT, 450 kcal) with
      regular satiety assessments and blood samples for appetite-related hormones
      commenced. An ad libitum meal was served after the MMTT, with subsequent
      calculation of energy-intake. Moreover, free-living diet records were completed
      for the following ~32 h. Exercise interventions were well-matched for mean oxygen
      consumption (CW = 77 +/- 2% of VO2peak; IW = 76 +/- 1% of VO2peak, P > 0.05). No
      differences in appetite-related hormones or energy-intake were found (P > 0.05
      for all comparisons). IW increased fullness compared to Control shortly after the
      intervention (P < 0.05) and tended to reduce hunger 2 h into the MMTT compared to
      CW and Control (P < 0.10). In conclusion, a single exercise session does not
      affect energy-intake during the following ~4-36 h in subjects with T2D. However,
      satiety may be affected up to ~3 h after the exercise session, dependent on peak
      intensity.

PMID- 29208687
TI  - Increased autophagy signaling but not proteasome activity in human skeletal
      muscle after prolonged low-intensity exercise with negative energy balance.
AB  - Little is known about the molecular regulation of skeletal muscle protein
      turnover during exercise in field conditions where energy is intake inadequate.
      Here, 17 male and 7 female soldiers performed an 8 days long field-based military
      operation. Vastus lateralis muscle biopsies, in which autophagy, the ubiquitin
      proteasome system, and the mTORC1 signaling pathway were studied, were collected
      before and after the operation. The 187 h long operation resulted in a 15% and
      29% negative energy balance as well as a 4.1% and 4.6% loss of body mass in women
      and men, respectively. After the operation protein levels of ULK1 as well as the
      phosphorylation of ULK1Ser317 and ULK1Ser555 had increased by 11%, 39%, and 13%,
      respectively, and this was supported by a 17% increased phosphorylation of
      AMPKThr172 (P < 0.05). The LC3b-I/II ratio was threefold higher after compared to
      before the operation (P < 0.05), whereas protein levels of p62/SQSTM1 were
      unchanged. The beta1, beta2, and beta5 activity of the proteasome and protein
      levels of MAFbx did not change, whereas levels of MuRF-1 were slightly reduced
      (6%, P < 0.05). Protein levels and phosphorylation status of key components in
      the mTORC1 signaling pathway remained at basal levels after the operation. Muscle
      levels of glycogen decreased from 269 +/- 12 to 181 +/- 9 mmol.kg dry.muscle-1
      after the exercise period (P < 0.05). In conclusion, the 8 days of field-based
      exercise resulted in induction of autophagy without any increase in proteasome
      activity or protein ubiquitination. Simultaneously, the regulation of protein
      synthesis through the mTORC1 signaling pathway was maintained.

PMID- 29208690
TI  - Aortic hemodynamics in postmenopausal women following cessation of hormone
      therapy.
AB  - Central (aortic) blood pressure and aortic pulse wave characteristics are
      measures of cardiovascular health, predictive of cardiovascular mortality.
      Previous studies have compared aortic hemodynamics in women who do and do not
      take menopausal hormone therapy, but characteristics of these parameters
      following cessation of treatment have not been defined. Therefore, the purpose of
      this study was to define aortic pulse wave characteristics in postmenopausal
      women with and without a history of menopausal hormone therapy use. Pulse wave
      analysis was conducted on 67 women who had participated in the randomized, double
      blind, placebo-controlled Kronos Early Estrogen Prevention Study (KEEPS), 3 years
      subsequent to the four-year treatment period. Treatment was oral conjugated
      equine estrogen (0.45 mg/day; n = 18); transdermal 17beta-estradiol (50 MUg/day;
      n = 23) each with oral micronized progesterone (Prometrium 200 mg); and placebo
      pills and patch (n = 26). At post-treatment, median age (60 years) and body mass
      index (27 kg/m2) did not differ across prior treatment assignment. Aortic blood
      pressures (median systolic 115 mm Hg and diastolic 76 mm Hg) and augmentation
      index (median 33%) did not differ among women across prior treatment assignment.
      These results suggest that these doses and formulations of menopausal hormone
      therapy had no long-term effects on central vascular function 3 years after
      cessation of treatment.

PMID- 29208689
TI  - Gestation changes sodium pump isoform expression, leading to changes in ouabain
      sensitivity, contractility, and intracellular calcium in rat uterus.
AB  - Developmental and tissue-specific differences in isoforms allow Na+, K+-ATPase
      function to be tightly regulated, as they control sensitivity to ions and
      inhibitors. Uterine contraction relies on the activity of the Na+, K+ATPase,
      which creates ionic gradients that drive excitation-contraction coupling. It is
      unknown whether Na+, K+ATPase isoforms are regulated throughout pregnancy or
      whether they have a direct role in modulating uterine contractility. We
      hypothesized that gestation-dependent differential expression of isoforms would
      affect contractile responses to Na+, K+ATPase alpha subunit inhibition with
      ouabain. Our aims were therefore: (1) to determine the gestation-dependent
      expression of mRNA transcripts, protein abundance and tissue distribution of Na+,
      K+ATPase isoforms in myometrium; (2) to investigate the functional effects of
      differential isoform expression via ouabain sensitivity; and (3) if changes in
      contractile responses can be explained by changes in intracellular [Ca2+].
      Changes in abundance and distribution of the Na+, K+ATPase alpha, beta and FXYD1
      and 2 isoforms, were studied in rat uterus from nonpregnant, and early, mid-, and
      term gestation. All alpha, beta subunit isoforms (1,2,3) and FXYD1 were detected
      but FXYD2 was absent. The alpha1 and beta1 isoforms were unchanged throughout
      pregnancy, whereas alpha2 and alpha3 significant decreased at term while beta2
      and FXYD1 significantly increased from mid-term onwards. These changes in
      expression correlated with increased functional sensitivity to ouabain, and
      parallel changes in intracellular Ca2+, measured with Indo-1. In conclusion,
      gestation induces specific regulatory changes in expression of Na+, K+ATPase
      isoforms in the uterus which influence contractility and may be related to the
      physiological requirements for successful pregnancy and delivery.

PMID- 29208691
TI  - Inhibition of nitric oxide synthase unmasks vigorous vasoconstriction in
      established pulmonary arterial hypertension.
AB  - It is widely accepted that impaired bioavailability of endothelial nitric oxide
      (NO) plays a critical role in the pathophysiology of pulmonary arterial
      hypertension (PAH). However, there are published data that show that relatively
      many PAH patients respond favorably to acetylcholine-induced pulmonary
      vasodilation during their follow-up period, when diverse stages of the disorder
      are included. We hypothesized that NO bioavailability varies depending on the
      progression of PAH Adult rats were exposed to the VEGF receptor blocker Sugen5416
      and 3 weeks of hypoxia followed by return to normoxia for various additional
      weeks. All rats developed increased right ventricular systolic pressure (RVSP)
      and occlusive lesion formation at 1, 3, 5, and 8 weeks after the Sugen5416
      injection. Acute NO synthase blockade did not change the elevated RVSP at the 1
      week time point, while it further increased RVSP markedly at the 3-, 5-, and 8
      week time points, leading to death in all rats tested at 8 weeks. Acetylcholine
      caused significant reduction in RVSP at the 8-week but not the 1-week time point,
      whereas sodium nitroprusside decreased the pressure similarly at both time
      points. Increased NO-mediated cGMP production was found in lungs from the 8-week
      but not the 1-week time point. In conclusion, despite its initial impairment, NO
      bioavailability is restored and endogenous NO plays a critical protective role by
      counteracting severe pulmonary vasoconstriction in established stages of PAH in
      the Sugen5416/hypoxia/normoxia-exposed rats. Our results provide solid
      pharmacological evidence for a major contribution of a NO-suppressed
      vasoconstrictor component in the pathophysiology of established PAH.

PMID- 29208692
TI  - Exercise-induced irisin release as a determinant of the metabolic response to
      exercise training in obese youth: the EXIT trial.
AB  - The mechanisms underlying the metabolic improvements following aerobic exercise
      training remain poorly understood. The primary aim of this study was to determine
      if an adipomyokine, irisin, responded to acute exercise was associated with the
      metabolic adaptations to chronic aerobic exercise in obese youth. The acute
      response to exercise was assessed in 11 obese youth following 45-min acute bouts
      of aerobic (AE) and resistance exercise (RE). The irisin area under the curve
      (pre-exercise, 15, 30, and 45 min) during these AE sessions were the main
      exposure variables. The primary outcome measure was the change in insulin
      sensitivity using the Matsuda index, following 6 weeks of RE training, delivered
      for 45 min, three times per week at 60-65% 1RM. Participants were also
      categorized as either responders (above) or nonresponders (below) based on the
      percentage change in the Matsuda index following the 6-week intervention. Irisin
      increased significantly during the acute bout of AE from 29.23 +/- 6.96 to 39.30
      +/- 7.05 ng/mL; P = 0.028, but not significantly during the RE session (P =
      0.182). Absolute and relative change in irisin during the acute bout of AE was
      associated with absolute and relative change in Matsuda index (r = 0.68; P =
      0.022 and r = 0.63; P = 0.037) following the 6-week RE intervention. No such
      association was observed with the irisin response to acute RE (all P > 0.05).
      Responders to the 6-week RE intervention displayed a fourfold greater irisin
      response to acute AE (90.0 +/- 28.0% vs. 22.8 +/- 18.7%; P = 0.024) compared to
      nonresponders. Irisin increases significantly following an acute bout of AE, but
      not RE, and this response is associated with a greater improvement in insulin
      sensitivity in response to chronic resistance training.

PMID- 29208694
TI  - Variation in Care and Clinical Outcomes in Children Hospitalized With Orbital
      Cellulitis.
AB  - OBJECTIVES: To describe variation in the care of children hospitalized with
      orbital cellulitis and to determine associations with length of stay (LOS),
      emergency department (ED) revisits, and hospital readmissions. METHODS: By using
      the Pediatric Health Information System, we performed a multicenter,
      retrospective study of children aged 2 months to 18 years with a primary
      International Classification of Diseases, Ninth Revision, Clinical Modification
      discharge diagnosis code for orbital cellulitis from 2007 to 2014. We assessed
      hospital-level variation in the use of diagnostic tests, corticosteroids, and
      antibiotics individually and in aggregate for association with outcomes (LOS, ED
      revisits, readmissions) after risk-adjusting for important clinical and
      demographic factors. RESULTS: A total of 1828 children met inclusion criteria.
      Complete blood cell counts (median [interquartile range]: 81.8% [66.7-89.6]), C
      reactive protein levels (57.1% [22.2-84.0]), blood cultures (57.9% [48.9-63.6]),
      and computed tomography imaging (74.7% [66.7-81.0]) were the most frequently
      performed diagnostic tests, with significant variation observed across hospitals
      (all P < .001). Corticosteroids were used in 29.2% of children (interquartile
      range: 18.4-37.5). There was significant variation in antibiotic exposure across
      hospitals (P < .001). Increased total diagnostic test usage was associated with
      increased LOS (P = .044), but not with 30-day ED revisits (P = .176) or
      readmissions (P = .403). CONCLUSIONS: Children hospitalized with orbital
      cellulitis experience wide variation in clinical management. Increased hospital
      level usage is associated with increased LOS. Our findings highlight a critical
      need to identify treatment strategies that optimize resource use and outcomes for
      children hospitalized with orbital cellulitis.

PMID- 29208693
TI  - Dysregulation of junctional adhesion molecule-A contributes to ethanol-induced
      barrier disruption in intestinal epithelial cell monolayers.
AB  - Alcohol consumption promotes loss of intestinal barrier function. However,
      mechanisms by which ethanol affects the tight junction (TJ), the cellular
      structure responsible for maintaining the gut epithelial barrier, are not well
      understood. Three classes of transmembrane proteins comprise TJs: occludin,
      claudins, and junctional adhesion molecules (JAMs). It has recently been
      postulated that JAM-A (F11R), the most abundant JAM expressed in intestinal
      epithelium, regulates "leak" pathway flux, a paracellular route for the
      nonselective permeation of large solutes. Since transluminal flux of many gut
      derived antigens occurs through this pathway, we investigated the role of JAM-A
      in ethanol-induced disruption of the intestinal epithelial barrier. Using Caco-2
      and SK-CO15 monolayers, we found that ethanol induced a dose- and time-dependent
      decrease in JAM-A protein expression to about 70% of baseline levels. Alcohol
      also reduced Ras-related protein 2 (Rap2) activity, and enhanced myosin light
      chain kinase (MLCK) activity, changes consistent with impaired JAM-A signaling.
      Stable overexpression and shRNA-mediated knockdown of JAM-A were employed to
      investigate the role of JAM-A in paracellular-mediated flux following alcohol
      exposure. The paracellular flux of 40-kDa fluorescein isothiocynate (FITC)
      dextran following ethanol treatment was decreased by the overexpression of JAM-A;
      conversely, flux was enhanced by JAM-A knockdown. Thus, we conclude that ethanol
      mediated control of JAM-A expression and function contributes to mechanisms by
      which this chemical induces intestinal epithelial leakiness.

PMID- 29208695
TI  - 2017 Jack Kenney Award for Outstanding Service.

PMID- 29208696
TI  - Acetyl-CoA carboxylase 1 regulates endothelial cell migration by shifting the
      phospholipid composition.
AB  - The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid
      metabolism. In recent years, ACC has been recognized as a promising drug target
      for treating different diseases. However, the role of ACC in vascular endothelial
      cells (ECs) has been neglected so far. To characterize the role of ACC, we used
      the ACC inhibitor, soraphen A, as a chemical tool, and also a gene silencing
      approach. We found that ACC1 was the predominant isoform in human umbilical vein
      ECs as well as in human microvascular ECs and that soraphen A reduced the levels
      of malonyl-CoA. We revealed that ACC inhibition shifted the lipid composition of
      EC membranes. Accordingly, membrane fluidity, filopodia formation, and migratory
      capacity were reduced. The antimigratory action of soraphen A depended on an
      increase in the cellular proportion of PUFAs and, most importantly, on a
      decreased level of phosphatidylglycerol. Our study provides a causal link between
      ACC, membrane lipid composition, and cell migration in ECs. Soraphen A represents
      a useful chemical tool to investigate the role of fatty acid metabolism in ECs
      and ACC inhibition offers a new and valuable therapeutic perspective for the
      treatment of EC migration-related diseases.

PMID- 29208697
TI  - Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of
      acute epileptic seizure model compared to controls.
AB  - In this study, we report the development of a dual extraction protocol for RNA
      and lipids, including phospholipids, endocannabinoids, and arachidonic acid, at
      high spatial resolution, e.g., brain punches obtained from whole frozen brains
      corresponding to four brain subregions: dorsal hippocampus, ventral hippocampus,
      basolateral amygdala, and hypothalamus. This extraction method combined with
      LC/multiple reaction monitoring for lipid quantifi-cation and quantitative PCR
      for RNA investigation allows lipidomic and transcriptomic profiling from
      submilligram amounts of tissue, thus benefiting the time and animal costs for
      analysis and the data reliability due to prevention of biological variability
      between animal batches and/or tissue heterogeneity, as compared with profiling in
      distinct animal batches. Moreover, the method allows a higher extraction
      efficiency and integrity preservation for RNA, while allowing concurrently
      quantitative analysis of low and high abundant lipids. The method was applied for
      brain punches obtained 1 h after kainic acid-induced epileptic seizures in mice
      (n = 10) compared with controls (n = 10), and enabled the provision of valuable
      new insights into the subregional lipid and RNA changes with epilepsy,
      highlighting its potential as a new viable tool in quantitative neurobiology.

PMID- 29208698
TI  - Arginine 123 of apolipoprotein A-I is essential for lecithin:cholesterol
      acyltransferase activity.
AB  - ApoA-I activates LCAT that converts lipoprotein cholesterol to cholesteryl ester
      (CE). Molecular dynamic simulations suggested earlier that helices 5 of two
      antiparallel apoA-I molecules on discoidal HDL form an amphipathic tunnel for
      migration of acyl chains and unesterified cholesterol to the active sites of
      LCAT. Our recent crystal structure of Delta(185-243)apoA-I showed the tunnel
      formed by helices 5/5, with two positively charged residues arginine 123
      positioned at the edge of the hydrophobic tunnel. We hypothesized that these
      uniquely positioned residues Arg123 are poised for interaction with fatty acids
      produced by LCAT hydrolysis of the sn-2 chains of phosphatidylcholine, thus
      positioning the fatty acids for esterification to cholesterol. To test the
      importance of Arg123 for LCAT phospholipid hydrolysis and CE formation, we
      generated apoA-I[R123A] and apoA-I[R123E] mutants and made discoidal HDL with the
      mutants and WT apoA-I. Neither mutation of Arg123 changed the particle
      composition or size, or the protein conformation or stability. However, both
      mutations of Arg123 significantly reduced LCAT catalytic efficiency and the
      apparent Vmax for CE formation without affecting LCAT phospholipid hydrolysis. A
      control mutation, apoA-I[R131A], did not affect LCAT phospholipid hydrolysis or
      CE formation. These data suggest that Arg123 of apoA-I on discoidal HDL
      participates in LCAT-mediated cholesterol esterification.

PMID- 29208699
TI  - Regulation of fatty acid trafficking in liver by thioesterase superfamily member
      1.
AB  - Thioesterase superfamily member 1 (Them1) is an acyl-CoA thioesterase that is
      highly expressed in brown adipose tissue, where it functions to suppress energy
      expenditure. Lower Them1 expression levels in the liver are upregulated in
      response to high-fat feeding. Them1-/- mice are resistant to diet-induced
      obesity, hepatic steatosis, and glucose intolerance, but the contribution of
      Them1 in liver is unclear. To examine its liver-specific functions, we created
      conditional transgenic mice, which, when bred to Them1-/- mice and activated,
      expressed Them1 exclusively in the liver. Mice with liver-specific Them1
      expression exhibited no changes in energy expenditure. Rates of fatty acid
      oxidation were increased, whereas hepatic VLDL triglyceride secretion rates were
      decreased by hepatic Them1 expression. When fed a high-fat diet, Them1 expression
      in liver promoted excess steatosis in the setting of reduced rates of fatty acid
      oxidation and preserved glycerolipid synthesis. Liver-specific Them1 expression
      did not influence glucose tolerance or insulin sensitivity, but did promote
      hepatic gluconeogenesis in high-fat-fed animals. This was attributable to the
      generation of excess fatty acids, which activated PPARalpha and promoted
      expression of gluconeogenic genes. These findings reveal a regulatory role for
      Them1 in hepatocellular fatty acid trafficking.

PMID- 29208700
TI  - Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5.
AB  - G protein-mediated signaling plays a decisive role in blood pressure regulation
      and the phenotype of vascular smooth muscle cells (VSMCs); however, the relevance
      of proteins that restrict G protein activity is not well characterized in this
      context. Here, we investigated the influence of regulator of G protein signaling
      5 (RGS5), an inhibitor of Galphaq/11 and Galphai/o activity, on blood pressure
      and the VSMC phenotype during experimental hypertension. In mice, loss of RGS5
      did not affect baseline blood pressure, but prevented hypertension-induced
      structural remodeling. RGS5-deficient arterial VSMCs did not acquire a synthetic
      phenotype as evidenced by their inability to decrease the abundance of
      contractile markers-alpha-smooth muscle actin and smooth muscle-myosin heavy
      chain-or to proliferate under these conditions. Mechanistically, hypertensive
      pressure levels or biomechanical stretch are sufficient to increase the
      expression of RGS5. Loss of RGS5 severely impairs the activation of RhoA and
      stress fiber formation. In stretch-exposed VSMCs, RhoA activity was amplified
      upon inhibition of PKC, which mimics the downstream effects evoked by RGS5
      mediated inhibition of Galphaq/11 signaling. Collectively, our findings underline
      that RhoA activation may depend on the restriction of G protein activity and
      identify RGS5 as a mechanosensitive regulatory protein that is required to
      promote the synthetic VSMC phenotype as a prerequisite for structural renovation
      of the arterial wall during hypertension.-Arnold, C., Demirel, E., Feldner, A.,
      Genove, G., Zhang, H., Sticht, C., Wieland, T., Hecker, M., Heximer, S., Korff,
      T. Hypertension-evoked RhoA activity in vascular smooth muscle cells requires
      RGS5.

PMID- 29208701
TI  - Interleukin-23 regulates interleukin-17 expression in wounds, and its inhibition
      accelerates diabetic wound healing through the alteration of macrophage
      polarization.
AB  - Inflammation is a critical phase in the healing of skin wounds. Excessive
      inflammation and inflammatory macrophages are known to cause impaired wound
      closure and outcome. This prompted us to test the role of IL-23 in IL-17
      expression and in modulating wound inflammation and macrophage polarization. Full
      thickness wounds (4 * 6 mm) were created on the dorsal surface of multiple
      genetically modified mouse models. Obese diabetic mouse wounds were treated with
      anti-IL-17A, anti-IL-23, or isotype-matched antibodies. We found IL-23- but not
      IL-12-deficient mice displayed significantly reduced IL-17 expression in wounds.
      This was rescued by delivery of recombinant IL-23. IL-23- and IL-17-deficient
      mice showed a significant increase in noninflammatory macrophages. Obese diabetic
      mice treated with anti-IL-17A and anti-IL-23p19 blocking antibodies had
      significantly improved wound reepithelialization. Similarly, IL-17-/- obese mice
      had accelerated wound closure, resulting in reduced iNOS expression and
      inflammatory macrophages while maintaining prohealing CD206 and lymphatic vessel
      endothelial hyaluronic acid receptor 1 (LYVE1)-expressing macrophages. This study
      highlights the importance of the IL-17 pathway in wound closure offering new
      possibilities of therapeutic intervention in chronic wounds.-Lee, J., Rodero, M.
      P., Patel, J., Moi, D., Mazzieri, R., Khosrotehrani, K. Interleukin-23 regulates
      interleukin-17 expression in wounds, and its inhibition accelerates diabetic
      wound healing through the alteration of macrophage polarization.

PMID- 29208702
TI  - Biochemistry and structural studies of kynurenine 3-monooxygenase reveal
      allosteric inhibition by Ro 61-8048.
AB  - The human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for
      neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a
      potent, selective, and the most widely used inhibitor of KMO, was shown effective
      in various models of neurodegenerative or neurologic disorders. However, the
      molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood. Here,
      we report biochemistry studies on hKMO and crystal structures of an hKMO homolog,
      pfKMO from Pseudomonas fluorescens, in complex with the substrate l-kynurenine
      and Ro 61-8048. We found that the C-terminal ~110 aa are essential for the
      enzymatic activity of hKMO and the homologous C-terminal region of pfKMO folds
      into a distinct, all-alpha-helical domain, which associates with the N-terminal
      catalytic domain to form a unique tunnel in proximity to the substrate-binding
      pocket. The tunnel binds the Ro 61-8048 molecule, which fills most of the tunnel,
      and Ro 61-8048 is hydrogen bonded with several completely conserved residues,
      including an essential catalytic residue. Modification of Ro 61-8048 and
      biochemical studies of the modified Ro 61-8048 derivatives suggested that Ro 61
      8048 inhibits the enzyme in an allosteric manner by affecting the conformation of
      the essential catalytic residue and by blocking entry of the substrate or product
      release. The unique binding sites distinguish Ro 61-8048 as a noncompetitive and
      highly selective inhibitor from other competitive inhibitors, which should
      facilitate further optimization of Ro 61-8048 and the development of new
      inhibitory drugs to hKMO.-Gao, J., Yao, L., Xia, T., Liao, X., Zhu, D., Xiang, Y.
      Biochemistry and structural studies of kynurenine 3-monooxygenase reveal
      allosteric inhibition by Ro 61-8048.

PMID- 29208704
TI  - Increased Phosphorylation of Ser-Gln Sites on SUPPRESSOR OF GAMMA RESPONSE1
      Strengthens the DNA Damage Response in Arabidopsis thaliana.
AB  - The Arabidopsis thaliana transcription factor SUPPRESSOR OF GAMMA RESPONSE1
      (SOG1) regulates hundreds of genes in response to DNA damage, and this results in
      the activation of cell cycle arrest, DNA repair, endoreduplication, and
      programmed cell death. However, it is not clear how this single transcription
      factor regulates each of these pathways. We previously reported that
      phosphorylation of five Ser-Gln (SQ) motifs in the C-terminal region of SOG1 are
      required to activate downstream pathways. In this study, we introduced Ser-to-Ala
      (AQ) substitutions in these five SQ motifs to progressively eliminate them and
      then we examined the effects on DNA damage responses. We found that all SQs are
      required for the full activation of SOG1 and that the expression level of most
      downstream genes changed incrementally depending on the number of phosphorylated
      SQ sites. Genes involved in DNA repair and cell cycle progression underwent
      stepwise activation and inhibition respectively as the number of phosphorylated
      SQ sites increased. Also, inhibition of DNA synthesis, programmed cell death, and
      cell differentiation were incrementally induced as the number of phosphorylated
      SQ sites increased. These results show that the extent of SQ phosphorylation in
      SOG1 regulates gene expression levels and determines the strength of DNA damage
      responses.

PMID- 29208703
TI  - DISTAG/TBCCd1 Is Required for Basal Cell Fate Determination in Ectocarpus.
AB  - Brown algae are one of the most developmentally complex groups within the
      eukaryotes. As in many land plants and animals, their main body axis is
      established early in development, when the initial cell gives rise to two
      daughter cells that have apical and basal identities, equivalent to shoot and
      root identities in land plants, respectively. We show here that mutations in the
      Ectocarpus DISTAG (DIS) gene lead to loss of basal structures during both the
      gametophyte and the sporophyte generations. Several abnormalities were observed
      in the germinating initial cell in dis mutants, including increased cell size,
      disorganization of the Golgi apparatus, disruption of the microtubule network,
      and aberrant positioning of the nucleus. DIS encodes a TBCCd1 protein, which has
      a role in internal cell organization in animals, Chlamydomonas reinhardtii, and
      trypanosomes. Our study highlights the key role of subcellular events within the
      germinating initial cell in the determination of apical/basal cell identities in
      a brown alga and emphasizes the remarkable functional conservation of TBCCd1 in
      regulating internal cell organization across extremely distant eukaryotic groups.

PMID- 29208705
TI  - An amazing meeting arrangement on messenger RNA genes.

PMID- 29208706
TI  - miPrimer: an empirical-based qPCR primer design method for small noncoding
      microRNA.
AB  - MicroRNAs (miRNAs) are 18-25 nucleotides (nt) of highly conserved, noncoding RNAs
      involved in gene regulation. Because of miRNAs' short length, the design of miRNA
      primers for PCR amplification remains a significant challenge. Adding to the
      challenge are miRNAs similar in sequence and miRNA family members that often only
      differ in sequences by 1 nt. Here, we describe a novel empirical-based method,
      miPrimer, which greatly reduces primer dimerization and increases primer
      specificity by factoring various intrinsic primer properties and employing four
      primer design strategies. The resulting primer pairs displayed an acceptable qPCR
      efficiency of between 90% and 110%. When tested on miRNA families, miPrimer
      designed primers are capable of discriminating among members of miRNA families,
      as validated by qPCR assays using Quark Biosciences' platform. Of the 120 miRNA
      primer pairs tested, 95.6% and 93.3% were successful in amplifying specifically
      non-family and family miRNA members, respectively, after only one design trial.
      In summary, miPrimer provides a cost-effective and valuable tool for designing
      miRNA primers.

PMID- 29208707
TI  - Recurring infection with ecologically distinct HPV types can explain high
      prevalence and diversity.
AB  - The high prevalence of human papillomavirus (HPV), the most common sexually
      transmitted infection, arises from the coexistence of over 200 genetically
      distinct types. Accurately predicting the impact of vaccines that target multiple
      types requires understanding the factors that determine HPV diversity. The
      diversity of many pathogens is driven by type-specific or "homologous" immunity,
      which promotes the spread of variants to which hosts have little immunity. To
      test for homologous immunity and to identify mechanisms determining HPV
      transmission, we fitted nonlinear mechanistic models to longitudinal data on
      genital infections in unvaccinated men. Our results provide no evidence for
      homologous immunity, instead showing that infection with one HPV type strongly
      increases the risk of infection with that type for years afterward. For HPV16,
      the type responsible for most HPV-related cancers, an initial infection increases
      the 1-year probability of reinfection by 20-fold, and the probability of
      reinfection remains 14-fold higher 2 years later. This increased risk occurs in
      both sexually active and celibate men, suggesting that it arises from
      autoinoculation, episodic reactivation of latent virus, or both. Overall, our
      results suggest that high HPV prevalence and diversity can be explained by a
      combination of a lack of homologous immunity, frequent reinfections, weak
      competition between types, and variation in type fitness between host
      subpopulations. Because of the high risk of reinfection, vaccinating boys who
      have not yet been exposed may be crucial to reduce prevalence, but our results
      suggest that there may also be large benefits to vaccinating previously infected
      individuals.

PMID- 29208708
TI  - Aminoglycoside interactions and impacts on the eukaryotic ribosome.
AB  - Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target
      functional centers within the bacterial ribosome to impact all four principle
      stages (initiation, elongation, termination, and recycling) of the translation
      mechanism. The propensity of aminoglycosides to induce miscoding errors that
      suppress the termination of protein synthesis supports their potential as
      therapeutic interventions in human diseases associated with premature termination
      codons (PTCs). However, the sites of interaction of aminoglycosides with the
      eukaryotic ribosome and their modes of action in eukaryotic translation remain
      largely unexplored. Here, we use the combination of X-ray crystallography and
      single-molecule FRET analysis to reveal the interactions of distinct classes of
      aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S
      ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007,
      solved at 3.3- to 3.7-A resolution, reveal multiple aminoglycoside-binding sites
      within the large and small subunits, wherein the 6'-hydroxyl substituent in ring
      I serves as a key determinant of binding to the canonical eukaryotic ribosomal
      decoding center. Multivalent binding interactions with the human ribosome are
      also evidenced through their capacity to affect large-scale conformational
      dynamics within the pretranslocation complex that contribute to multiple aspects
      of the translation mechanism. The distinct impacts of the aminoglycosides
      examined suggest that their chemical composition and distinct modes of
      interaction with the ribosome influence PTC read-through efficiency. These
      findings provide structural and functional insights into aminoglycoside-induced
      impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action
      beyond decoding.

PMID- 29208710
TI  - Transverse fields to tune an Ising-nematic quantum phase transition.
AB  - The paradigmatic example of a continuous quantum phase transition is the
      transverse field Ising ferromagnet. In contrast to classical critical systems,
      whose properties depend only on symmetry and the dimension of space, the nature
      of a quantum phase transition also depends on the dynamics. In the transverse
      field Ising model, the order parameter is not conserved, and increasing the
      transverse field enhances quantum fluctuations until they become strong enough to
      restore the symmetry of the ground state. Ising pseudospins can represent the
      order parameter of any system with a twofold degenerate broken-symmetry phase,
      including electronic nematic order associated with spontaneous point-group
      symmetry breaking. Here, we show for the representative example of orbital
      nematic ordering of a non-Kramers doublet that an orthogonal strain or a
      perpendicular magnetic field plays the role of the transverse field, thereby
      providing a practical route for tuning appropriate materials to a quantum
      critical point. While the transverse fields are conjugate to seemingly unrelated
      order parameters, their nontrivial commutation relations with the nematic order
      parameter, which can be represented by a Berry-phase term in an effective field
      theory, intrinsically intertwine the different order parameters.

PMID- 29208709
TI  - Conserved salt-bridge competition triggered by phosphorylation regulates the
      protein interactome.
AB  - Phosphorylation is a major regulator of protein interactions; however, the
      mechanisms by which regulation occurs are not well understood. Here we identify a
      salt-bridge competition or "theft" mechanism that enables a phospho-triggered
      swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP
      transitions from inhibiting Raf-1 to inhibiting G-protein-coupled receptor kinase
      2 upon phosphorylation, thereby bridging MAP kinase and G-Protein-Coupled
      Receptor signaling. NMR and crystallography indicate that a phosphoserine, but
      not a phosphomimetic, competes for a lysine from a preexisting salt bridge,
      initiating a partial unfolding event and promoting new protein interactions.
      Structural elements underlying the theft occurred early in evolution and are
      found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax,
      Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of
      phosphorylated residues by binding partners, the salt-bridge theft mechanism
      represents a facile strategy for promoting or disrupting protein interactions
      using solvent-accessible residues, and it can provide additional specificity at
      protein interfaces through local unfolding or conformational change.

PMID- 29208711
TI  - Molecular basis for the recognition of the human AAUAAA polyadenylation signal.
AB  - Nearly all eukaryotic messenger RNA precursors must undergo cleavage and
      polyadenylation at their 3'-end for maturation. A crucial step in this process is
      the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular
      mechanism of this recognition has been a long-standing problem. Here, we report
      the cryo-electron microscopy structure of a quaternary complex of human CPSF-160,
      WDR33, CPSF-30, and an AAUAAA RNA at 3.4-A resolution. Strikingly, the AAUAAA PAS
      assumes an unusual conformation that allows this short motif to be bound directly
      by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by
      zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the
      U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact
      WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and
      WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant
      molecular explanation for how PAS sequences are recognized for mRNA 3'-end
      formation.

PMID- 29208712
TI  - Crystal structure of human IRAK1.
AB  - Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine
      kinases that play critical roles in initiating innate immune responses against
      foreign pathogens and other types of dangers through their role in Toll-like
      receptor (TLR) and interleukin 1 receptor (IL-1R) mediated signaling pathways.
      Upon ligand binding, TLRs and IL-1Rs recruit adaptor proteins, such as myeloid
      differentiation primary response gene 88 (MyD88), to the membrane, which in turn
      recruit IRAKs via the death domains in these proteins to form the Myddosome
      complex, leading to IRAK kinase activation. Despite their biological and clinical
      significance, only the IRAK4 kinase domain structure has been determined among
      the four IRAK family members. Here, we report the crystal structure of the human
      IRAK1 kinase domain in complex with a small molecule inhibitor. The structure
      reveals both similarities and differences between IRAK1 and IRAK4 and is
      suggestive of approaches to develop IRAK1- or IRAK4-specific inhibitors for
      potential therapeutic applications. While the IRAK4 kinase domain is capable of
      homodimerization in the unphosphorylated state, we found that the IRAK1 kinase
      domain is constitutively monomeric regardless of its phosphorylation state.
      Additionally, the IRAK1 kinase domain forms heterodimers with the phosphorylated,
      but not unphosphorylated, IRAK4 kinase domain. Collectively, these data indicate
      a two-step kinase activation process in which the IRAK4 kinase domain first
      homodimerizes in the Myddosome, leading to its trans-autophosphorylation and
      activation. The phosphorylated IRAK4 kinase domain then forms heterodimers with
      the IRAK1 kinase domain within the Myddosome, leading to its subsequent
      phosphorylation and activation.

PMID- 29208714
TI  - Encoding model of temporal processing in human visual cortex.
AB  - How is temporal information processed in human visual cortex? Visual input is
      relayed to V1 through segregated transient and sustained channels in the retina
      and lateral geniculate nucleus (LGN). However, there is intense debate as to how
      sustained and transient temporal channels contribute to visual processing beyond
      V1. The prevailing view associates transient processing predominately with motion
      sensitive regions and sustained processing with ventral stream regions, while the
      opposing view suggests that both temporal channels contribute to neural
      processing beyond V1. Using fMRI, we measured cortical responses to time-varying
      stimuli and then implemented a two temporal channel-encoding model to evaluate
      the contributions of each channel. Different from the general linear model of
      fMRI that predicts responses directly from the stimulus, the encoding approach
      first models neural responses to the stimulus from which fMRI responses are
      derived. This encoding approach not only predicts cortical responses to time
      varying stimuli from milliseconds to seconds but also, reveals differential
      contributions of temporal channels across visual cortex. Consistent with the
      prevailing view, motion-sensitive regions and adjacent lateral occipitotemporal
      regions are dominated by transient responses. However, ventral occipitotemporal
      regions are driven by both sustained and transient channels, with transient
      responses exceeding the sustained. These findings propose a rethinking of
      temporal processing in the ventral stream and suggest that transient processing
      may contribute to rapid extraction of the content of the visual input.
      Importantly, our encoding approach has vast implications, because it can be
      applied with fMRI to decipher neural computations in millisecond resolution in
      any part of the brain.

PMID- 29208713
TI  - SbcC-SbcD and ExoI process convergent forks to complete chromosome replication.
AB  - SbcC-SbcD are the bacterial orthologs of Mre11-Rad50, a nuclease complex
      essential for genome stability, normal development, and viability in mammals. In
      vitro, these enzymes degrade long DNA palindromic structures. When inactivated
      along with ExoI in Escherichia coli, or Sae2 in eukaryotes, palindromic
      amplifications arise and propagate in cells. However, long DNA palindromes are
      not normally found in bacterial or human genomes, leaving the cellular substrates
      and function of these enzymes unknown. Here, we show that during the completion
      of DNA replication, convergent replication forks form a palindrome-like
      structural intermediate that requires nucleolytic processing by SbcC-SbcD and
      ExoI before chromosome replication can be completed. Inactivation of these
      nucleases prevents completion from occurring, and under these conditions, cells
      maintain viability by shunting the reaction through an aberrant recombinational
      pathway that leads to amplifications and instability in this region. The results
      identify replication completion as an event critical to maintain genome integrity
      and cell viability, demonstrate SbcC-SbcD-ExoI acts before RecBCD and is required
      to initiate the completion reaction, and reveal how defects in completion result
      in genomic instability.

PMID- 29208715
TI  - What Chern-Simons theory assigns to a point.
AB  - We answer the questions, "What does Chern-Simons theory assign to a point?" and
      "What kind of mathematical object does Chern-Simons theory assign to a point?"
      Our answer to the first question is representations of the based loop group. More
      precisely, we identify a certain class of projective unitary representations of
      the based loop group [Formula: see text] We define the fusion product of such
      representations, and we prove that, modulo certain conjectures, the Drinfel'd
      center of that representation category of [Formula: see text] is equivalent to
      the category of positive energy representations of the free loop group [Formula:
      see text]? The abovementioned conjectures are known to hold when the gauge group
      is abelian or of type [Formula: see text] Our answer to the second question is
      bicommutant categories. The latter are higher categorical analogs of von Neumann
      algebras: They are tensor categories that are equivalent to their bicommutant
      inside [Formula: see text], the category of bimodules over a hyperfinite
      [Formula: see text] factor. We prove that, modulo certain conjectures, the
      category of representations of the based loop group is a bicommutant category.
      The relevant conjectures are known to hold when the gauge group is abelian or of
      type [Formula: see text].

PMID- 29208716
TI  - Direct measurements of meltwater runoff on the Greenland ice sheet surface.
AB  - Meltwater runoff from the Greenland ice sheet surface influences surface mass
      balance (SMB), ice dynamics, and global sea level rise, but is estimated with
      climate models and thus difficult to validate. We present a way to measure ice
      surface runoff directly, from hourly in situ supraglacial river discharge
      measurements and simultaneous high-resolution satellite/drone remote sensing of
      upstream fluvial catchment area. A first 72-h trial for a 63.1-km2 moulin
      terminating internally drained catchment (IDC) on Greenland's midelevation (1,207
      1,381 m above sea level) ablation zone is compared with melt and runoff
      simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models.
      Current models cannot reproduce peak discharges or timing of runoff entering
      moulins but are improved using synthetic unit hydrograph (SUH) theory.
      Retroactive SUH applications to two older field studies reproduce their findings,
      signifying that remotely sensed IDC area, shape, and supraglacial river length
      are useful for predicting delays in peak runoff delivery to moulins. Applying SUH
      to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs
      suggests their terminal moulins receive lower peak discharges, less diurnal
      variability, and asynchronous runoff timing relative to climate/SMB model output
      alone. Conversely, large IDCs produce high moulin discharges, even at high
      elevations where melt rates are low. During this particular field experiment,
      models overestimated runoff by +21 to +58%, linked to overestimated surface
      ablation and possible meltwater retention in bare, porous, low-density ice.
      Direct measurements of ice surface runoff will improve climate/SMB models, and
      incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and
      subglacial systems.

PMID- 29208717
TI  - Efficient targeted DNA editing and replacement in Chlamydomonas reinhardtii using
      Cpf1 ribonucleoproteins and single-stranded DNA.
AB  - The green alga Chlamydomonas reinhardtii is an invaluable reference organism to
      research fields including algal, plant, and ciliary biology. Accordingly, decades
      long standing inefficiencies in targeted nuclear gene editing broadly hinder
      Chlamydomonas research. Here we report that single-step codelivery of CRISPR/Cpf1
      ribonucleoproteins with single-stranded DNA repair templates results in precise
      and targeted DNA replacement with as much as ~10% efficiency in C. reinhardtii We
      demonstrate its use in transgene- and selection-free generation of sequence
      specific mutations and epitope tagging at an endogenous locus. As the direct
      delivery of gene-editing reagents bypasses the use of transgenes, this method is
      potentially applicable to a wider range of species without the need to develop
      methods for stable transformation.

PMID- 29208719
TI  - Effect of removing Kupffer cells on nanoparticle tumor delivery.
AB  - A recent metaanalysis shows that 0.7% of nanoparticles are delivered to solid
      tumors. This low delivery efficiency has major implications in the translation of
      cancer nanomedicines, as most of the nanomedicines are sequestered by nontumor
      cells. To improve the delivery efficiency, there is a need to investigate the
      quantitative contribution of each organ in blocking the transport of
      nanoparticles to solid tumors. Here, we hypothesize that the removal of the liver
      macrophages, cells that have been reported to take up the largest amount of
      circulating nanoparticles, would lead to a significant increase in the
      nanoparticle delivery efficiency to solid tumors. We were surprised to discover
      that the maximum achievable delivery efficiency was only 2%. In our analysis,
      there was a clear correlation between particle design, chemical composition,
      macrophage depletion, tumor pathophysiology, and tumor delivery efficiency. In
      many cases, we observed an 18-150 times greater delivery efficiency, but we were
      not able to achieve a delivery efficiency higher than 2%. The results suggest the
      need to look deeper at other organs such as the spleen, lymph nodes, and tumor in
      mediating the delivery process. Systematically mapping the contribution of each
      organ quantitatively will allow us to pinpoint the cause of the low tumor
      delivery efficiency. This, in effect, enables the generation of a rational
      strategy to improve the delivery efficiency of nanoparticles to solid tumors
      either through the engineering of multifunctional nanosystems or through
      manipulation of biological barriers.

PMID- 29208720
TI  - Reply to Hilborn: Role of marine reserves depends on assumptions.

PMID- 29208721
TI  - Traditional fisheries management is the best way to manage weak stocks.

PMID- 29208722
TI  - Reply to Hogan: Direct evidence of RNA-protein interactions and rewiring.

PMID- 29208718
TI  - An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES
      program on research outcomes and student learning.
AB  - Engaging undergraduate students in scientific research promises substantial
      benefits, but it is not accessible to all students and is rarely implemented
      early in college education, when it will have the greatest impact. An inclusive
      Research Education Community (iREC) provides a centralized scientific and
      administrative infrastructure enabling engagement of large numbers of students at
      different types of institutions. The Science Education Alliance-Phage Hunters
      Advancing Genomics and Evolutionary Science (SEA-PHAGES) is an iREC that promotes
      engagement and continued involvement in science among beginning undergraduate
      students. The SEA-PHAGES students show strong gains correlated with persistence
      relative to those in traditional laboratory courses regardless of academic,
      ethnic, gender, and socioeconomic profiles. This persistent involvement in
      science is reflected in key measures, including project ownership, scientific
      community values, science identity, and scientific networking.

PMID- 29208723
TI  - Clarifying results and prevailing models for the evolution of Puf proteins and
      their RNA targets.

PMID- 29208724
TI  - Reply to Nakov et al.: Model choice requires biological insight when studying the
      ancestral habitat of photosynthetic eukaryotes.

PMID- 29208725
TI  - Models with unequal transition rates favor marine origins of Cyanobacteria and
      photosynthetic eukaryotes.

PMID- 29208726
TI  - How Parents of Children With Cancer Learn About Their Children's Prognosis.
AB  - OBJECTIVES: To determine which prognostic information sources parents find
      informative and which are associated with better parental understanding of
      prognosis. METHODS: Prospective, questionnaire-based cohort study of parents and
      physicians of children with cancer at 2 academic pediatric hospitals. We asked
      parents how they learned about prognoses and evaluated relationships between
      information sources and prognostic understanding, defined as accuracy versus
      optimism. We excluded parents with pessimistic estimates and whose children had
      such good prognoses that optimism relative to the physician was impossible.
      Analytic cohort of 256 parent-physician pairs. RESULTS: Most parents considered
      explicit sources (conversations with oncologists at diagnosis, day-to-day
      conversations with oncologists, and conversations with nurses) "very" or
      "extremely" informative (73%-85%). Implicit sources (parent's sense of how child
      was doing or how oncologist seemed to feel child was doing) were similarly
      informative (84%-87%). Twenty-seven percent (70/253) of parents reported
      prognostic estimates matching physicians' estimates. Parents who valued implicit
      information had lower prognostic accuracy (odds ratio [OR] 0.50; 95% confidence
      interval 0.29-0.88), especially those who relied on a "general sense of how my
      child's oncologist seems to feel my child is doing" (OR 0.47; 0.22-0.99). Parents
      were more likely to use implicit sources if they reported receiving high-quality
      prognostic information (OR 3.02; 1.41-6.43), trusted the physician (OR 2.01; 1.01
      3.98), and reported high-quality physician communication (OR 1.81; 1.00-3.27).
      CONCLUSIONS: Reliance on implicit sources was associated with overly-optimistic
      prognostic estimates. Parents who endorsed strong, trusting relationships with
      physicians were not protected against misinformation.

PMID- 29208727
TI  - An Unusual Case of Abdominal Pain and Hyponatremia in a 16-Year-Old Girl With
      Disordered Eating.
AB  - A previously healthy 16-year-old girl presented to the emergency department with
      1 week of severe, diffuse abdominal pain and constipation, as well as several
      episodes of nonbloody, nonbilious emesis. Her symptoms began several days after
      she decreased her caloric intake in an attempt to lose weight. She had been
      drinking 48 to 60 oz of water per day for several days before admission in an
      attempt to ameliorate her constipation. She also admits to drinking alcohol the
      night before her pain began. She had visited several other emergency departments
      before her presentation to our hospital, and she had been sent home on a bowel
      regimen without amelioration of her symptoms. On arrival to our emergency
      department, she described severe diffuse abdominal pain. Her abdomen was tender
      to palpation throughout but soft with no rebound tenderness or peritoneal signs.
      The remainder of her physical examination yielded normal results. She was found
      to have hyponatremia with a sodium level of 122 and no neurologic sequelae.
      Abdominal radiograph showed moderate constipation but her abdominal pain
      continued even after bowel cleanout. The home, education, activities, drugs, sex,
      suicide, and safety assessment revealed several stressors, including a recent
      suicide in the family and a history of disordered eating and anxiety. Here, we
      present her case, diagnostic evaluation, ultimate diagnosis, and complications.

PMID- 29208728
TI  - Imaging in low-grade glioma: a guide for neurologists.
AB  - The management of low-grade glioma (LGG) is shifting as evidence has emergedthat
      refutes the previously commonplace imaging-based 'watch and wait' approach, in
      favour of early aggressive surgical resection. This coupled with the recent 2016
      update to the World Health Organisation Classification of Tumours of the Central
      Nervous System is changing LGG imaging and management. Recently in Practical
      Neurology the contemporary management of low-grade glioma and the changes to this
      grading system were discussed in detail. 1 In this complementary article, we
      discuss the role of imaging in the diagnosis, surgical planning and post
      treatment follow-up of LGG. We describe the principles of imaging these tumours
      and use several cases to highlight some difficult scenarios.

PMID- 29208729
TI  - Persistent postural-perceptual dizziness (PPPD): a common, characteristic and
      treatable cause of chronic dizziness.
AB  - Persistent postural-perceptual dizziness (PPPD) is a newly defined diagnostic
      syndrome that unifies key features of chronic subjective dizziness, phobic
      postural vertigo and related disorders. It describes a common chronic dysfunction
      of the vestibular system and brain that produces persistent dizziness, non
      spinning vertigo and/or unsteadiness. The disorder constitutes a long-term
      maladaptation to a neuro-otological, medical or psychological event that
      triggered vestibular symptoms, and is usefully considered within the spectrum of
      other functional neurological disorders. While diagnostic tests and conventional
      imaging usually remain negative, patients with PPPD present in a characteristic
      way that maps on to positive diagnostic criteria. Patients often develop
      secondary functional gait disorder, anxiety, avoidance behaviour and severe
      disability. Once recognised, PPPD can be managed with effective communication and
      tailored treatment strategies, including specialised physical therapy (vestibular
      rehabilitation), serotonergic medications and cognitive-behavioural therapy.

PMID- 29208731
TI  - Misleading signs in acute vertigo.
AB  - The acute vestibular syndrome is common and usually has a benign cause.
      Sometimes, however, even experienced neurologists can find it difficult to
      determine the cause clinically. Furthermore, neuroimaging is known to be
      insensitive.We describe two cases of acute vestibular syndrome where conflicting
      clinical findings contributed to a delay in making the correct diagnosis. The
      first patient with symptomatic vertigo had signs consistent with horizontal
      benign paroxysmal positional vertigo but also had an abnormal horizontal head
      impulse test, superficially suggesting acute vestibular neuritis but later
      accounted for by the finding of a vestibular schwannoma (acoustic neuroma). The
      second patient also had an abnormal horizontal head impulse test, with skew
      deviation suggesting stroke as the cause. However, later assessment identified
      that a long-standing fourth nerve palsy was the true cause for her apparent skew.
      We discuss potential errors that can arise when assessing such patients and
      highlight ways to avoid them.

PMID- 29208730
TI  - Rituximab for corticosteroid-resistant relapsing IgG4-related intracranial
      pachymeningitis: report of two cases.
AB  - IgG4-related disease is now recognised as an important cause of intracranial and
      spinal hypertrophic pachymeningitis. Treatment with corticosteroids generally
      leads to significant clinical improvement. We present two cases of IgG4
      pachymeningitis unresponsive to corticosteroids who improved with rituximab.

PMID- 29208733
TI  - Opinion: Building a better past with the help of agent-based modeling.

PMID- 29208732
TI  - The Next Generation of Training for Arabidopsis Researchers: Bioinformatics and
      Quantitative Biology.

PMID- 29208735
TI  - David Oliver: Seven day service standards in NHS hospitals: thorny problem or
      blooming success?

PMID- 29208737
TI  - Genetic influence on the associations between IGF-I and glucose metabolism in a
      cohort of elderly twins.
AB  - OBJECTIVE: IGF-I may be a marker of later metabolic and cardiovascular disease.
      The interactions between IGF-I and glucose metabolism are multifactorial, and
      there is potential confounding from several secondary effects. In this study, we
      examined the interaction between IGF-I and glucose metabolism in a large cohort
      of clinically well-characterized elderly twins. DESIGN: A total of 303 twin pairs
      of the same gender (606 twins) were included in the study; 125 monozygotic and
      178 dizygotic twin pairs. METHODS: A clinical examination including a standard
      oral glucose tolerance test (OGTT) and anthropometric measurements was performed.
      RESULTS: The heritability estimates were high for IGF-I and IGFBP-3 (h2: 0.65
      (95% CI: 0.55-0.74) and 0.71 (0.48-0.94), respectively) and for insulin secretion
      (h2 = 0.56, P < 0.0001), whereas the heritability estimates for insulin
      sensitivity were low (h2 = 0.14, P = 0.11). In a multiple regression analysis
      (adjusting for age, gender and twin status), there was a negative association
      between IGF-I and insulin sensitivity (B: -0.13, SE 0.03, P < 0.0001) and IGF-I
      and disposition index (B: -0.05, SE 0.02, P < 0.001) in the entire cohort of 606
      twins. The associations between IGF-I and both DI and HOMA-S did not differ
      between the DZ and MZ twins. Forty-five twin pairs were discordant for T2D, but
      the discordant twins had similar concentrations of IGF-I or IGFBP-3. CONCLUSIONS:
      There was a high heritability for IGF-I and IGFBP-3, but a low heritability for
      insulin secretion and insulin sensitivity in a group of elderly twins. In
      addition, we found a strong negative relationship between IGF-I and insulin
      sensitivity, which did not seem to be strongly genetically determined.

PMID- 29208738
TI  - A new form of nicotine retailers: a systematic review of the sales and marketing
      practices of vape shops.
AB  - OBJECTIVE: Retailers that primarily or exclusively sell electronic cigarettes (e
      cigarettes) or vaping products represent a new category of tobacco retailer. We
      sought to identify (a) how vape shops can be identified and (b) sales and
      marketing practices of vape shops. DATA SOURCES: A medical librarian iteratively
      developed a search strategy and in February 2017 searched seven academic
      databases (ABI/INFORM Complete, ECONLit, Embase, Entrepreneurship, PsycINFO,
      PubMed/MEDLINE and Scopus). We hand searched Tobacco Regulatory Science and
      Tobacco Prevention & Cessation. STUDY SELECTION: We used dual, independent
      screening. Records were eligible if published in 2010 or later, were peer
      reviewed journal articles and focused on vape shops. DATA EXTRACTION: We used
      dual, independent data abstraction and assessed risk of bias. Of the 3605 records
      identified, 22 were included. DATA SYNTHESIS: We conducted a narrative systematic
      review. Researchers relied heavily on Yelp to identify vape shops. Vape shop
      owners use innovative marketing strategies that sometimes diverge from those of
      traditional tobacco retailers. Vape shop staff believe strongly that their
      products are effective harm-reduction products. Vape shops were more common in
      areas with more White residents. CONCLUSIONS: Vape shops represent a new type of
      retailer for tobacco products. Vape shops have potential to promote e-cigarettes
      for smoking cessation but also sometimes provide inaccurate information and
      mislabelled products. Given their spatial patterning, vape shops may perpetuate
      inequities in tobacco use. The growing literature on vape shops is complicated by
      researchers using different definitions of vape shops (eg, exclusively selling e
      cigarettes vs also selling traditional tobacco products).

PMID- 29208739
TI  - Correlates of compliance with national comprehensive smoke-free laws.
AB  - OBJECTIVE: To explore correlates of high compliance with smoking bans in a cross
      sectional data set from the 41 countries with national comprehensive smoke-free
      laws in 2014 and complete data on compliance and enforcement. METHODS: Outcome
      variable: compliance with a national comprehensive smoke-free law in each country
      was obtained for 2014 from the WHO global report on the global tobacco epidemic.
      Explanatory variables: legal enforcement requirements, penalties, infrastructure
      and strategy were obtained through a separate survey of governments. Also,
      country socioeconomic and demographic characteristics including the level of
      corruption control were included. ANALYSIS: an initial bivariate analysis
      determined the significance of each potentially relevant explanatory variable of
      high compliance. Differences in compliance were tested using the exact logistic
      regression. RESULTS: High compliance with the national comprehensive smoke-free
      law was associated with the involvement of the local jurisdictions in providing
      training and/or guidance for inspections (OR=10.3, 95% CI 1.7 to 117.7) and a
      perception of high corruption control efforts in the country (OR=7.2, 95% CI 1.1
      to 85.8). DISCUSSION: The results show the importance of the depth of the
      enforcement infrastructure and effort represented by the degree to which the
      local government is involved in enforcement. They also show the significance of
      fighting corruption in the enforcement process, including the attempts of the
      tobacco industry to undermine the process, to achieve high levels of compliance
      with the law. The results point out to the need to invest minimal but essential
      enforcement resources given that national comprehensive smoke-free laws are self
      enforcing in many but not all countries and sectors.

PMID- 29208736
TI  - Pathophysiological and behavioral deficits in developing mice following
      rotational acceleration-deceleration traumatic brain injury.
AB  - Abusive head trauma (AHT) is the leading cause of death from trauma in infants
      and young children. An AHT animal model was developed on 12-day-old mice
      subjected to 90 degrees  head extension-flexion sagittal shaking repeated 30, 60,
      80 and 100 times. The mortality and time until return of consciousness were
      dependent on the number of repeats and severity of the injury. Following 60
      episodes of repeated head shakings, the pups demonstrated apnea and/or
      bradycardia immediately after injury. Acute oxygen desaturation was observed by
      pulse oximetry during respiratory and cardiac suppression. The cerebral blood
      perfusion was assessed by laser speckle contrast analysis (LASCA) using a PeriCam
      PSI system. There was a severe reduction in cerebral blood perfusion immediately
      after the trauma that did not significantly improve within 24 h. The injured mice
      began to experience reversible sensorimotor function at 9 days postinjury (dpi),
      which had completely recovered at 28 dpi. However, cognitive deficits and anxiety
      like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain
      blood barrier and parenchymal edema were found in all pups subjected to 60
      insults. Proinflammatory response and reactive gliosis were upregulated at 3 dpi.
      Degenerated neurons were found in the cerebral cortex and olfactory tubercles at
      30 dpi. This mouse model of repetitive brain injury by rotational head
      acceleration-deceleration partially mimics the major pathophysiological and
      behavioral events that occur in children with AHT. The resultant hypoxia/ischemia
      suggests a potential mechanism underlying the secondary rotational acceleration
      deceleration-induced brain injury in developing mice.

PMID- 29208740
TI  - Ecosystem Resilience and Limitations Revealed by Soil Bacterial Community
      Dynamics in a Bark Beetle-Impacted Forest.
AB  - Forested ecosystems throughout the world are experiencing increases in the
      incidence and magnitude of insect-induced tree mortality with large ecologic
      ramifications. Interestingly, correlations between water quality and the extent
      of tree mortality in Colorado montane ecosystems suggest compensatory effects
      from adjacent live vegetation that mute responses in less severely impacted
      forests. To this end, we investigated whether the composition of the soil
      bacterial community and associated functionality beneath beetle-killed lodgepole
      pine was influenced by the extent of surrounding tree mortality. The most
      pronounced changes were observed in the potentially active bacterial community,
      where alpha diversity increased in concert with surrounding tree mortality until
      mortality exceeded a tipping point of ~30 to 40%, after which diversity
      stabilized and decreased. Community structure also clustered in association with
      the extent of surrounding tree mortality with compositional trends best explained
      by differences in NH4+ concentrations and C/N ratios. C/N ratios, which were
      lower in soils under beetle-killed trees, further correlated with the relative
      abundance of putative nitrifiers and exoenzyme activity. Collectively, the
      response of soil microorganisms that drive heterotrophic respiration and decay
      supports observations of broader macroscale threshold effects on water quality in
      heavily infested forests and could be utilized as a predictive mechanism during
      analogous ecosystem disruptions.IMPORTANCE Forests around the world are
      succumbing to insect infestation with repercussions for local soil
      biogeochemistry and downstream water quality and quantity. This study utilized
      microbial community dynamics to address why we are observing watershed scale
      biogeochemical impacts from forest mortality in some impacted areas but not
      others. Through a unique "tree-centric" approach, we were able to delineate plots
      with various tree mortality levels within the same watershed to see if surviving
      surrounding vegetation altered microbial and biogeochemical responses. Our
      results suggest that forests with lower overall tree mortality levels are able to
      maintain "normal" ecosystem function, as the bacterial community appears
      resistant to tree death. However, surrounding tree mortality influences this
      mitigating effect with various linear and threshold responses whereupon the
      bacterial community and its function are altered. Our study lends insight into
      how microscale responses propagate upward into larger-scale observations, which
      may be useful for future predictions during analogous disruptions.

PMID- 29208741
TI  - Genome Sequences Reveal Cryptic Speciation in the Human Pathogen Histoplasma
      capsulatum.
AB  - Histoplasma capsulatum is a pathogenic fungus that causes life-threatening lung
      infections. About 500,000 people are exposed to H. capsulatum each year in the
      United States, and over 60% of the U.S. population has been exposed to the fungus
      at some point in their life. We performed genome-wide population genetics and
      phylogenetic analyses with 30 Histoplasma isolates representing four recognized
      areas where histoplasmosis is endemic and show that the Histoplasma genus is
      composed of at least four species that are genetically isolated and rarely
      interbreed. Therefore, we propose a taxonomic rearrangement of the
      genus.IMPORTANCE The evolutionary processes that give rise to new pathogen
      lineages are critical to our understanding of how they adapt to new environments
      and how frequently they exchange genes with each other. The fungal pathogen
      Histoplasma capsulatum provides opportunities to precisely test hypotheses about
      the origin of new genetic variation. We find that H. capsulatum is composed of at
      least four different cryptic species that differ genetically and also in
      virulence. These results have implications for the epidemiology of histoplasmosis
      because not all Histoplasma species are equivalent in their geographic range and
      ability to cause disease.

PMID- 29208742
TI  - Force-Induced Strengthening of the Interaction between Staphylococcus aureus
      Clumping Factor B and Loricrin.
AB  - Bacterial pathogens that colonize host surfaces are subjected to physical
      stresses such as fluid flow and cell surface contacts. How bacteria respond to
      such mechanical cues is an important yet poorly understood issue. Staphylococcus
      aureus uses a repertoire of surface proteins to resist shear stress during the
      colonization of host tissues, but whether their adhesive functions can be
      modulated by physical forces is not known. Here, we show that the interaction of
      S. aureus clumping factor B (ClfB) with the squamous epithelial cell envelope
      protein loricrin is enhanced by mechanical force. We find that ClfB mediates S.
      aureus adhesion to loricrin through weak and strong molecular interactions both
      in a laboratory strain and in a clinical isolate. Strong forces (~1,500 pN),
      among the strongest measured for a receptor-ligand bond, are consistent with a
      high-affinity "dock, lock, and latch" binding mechanism involving dynamic
      conformational changes in the adhesin. Notably, we demonstrate that the strength
      of the ClfB-loricrin bond increases as mechanical force is applied. These
      findings favor a two-state model whereby bacterial adhesion to loricrin is
      enhanced through force-induced conformational changes in the ClfB molecule, from
      a weakly binding folded state to a strongly binding extended state. This force
      sensitive mechanism may provide S. aureus with a means to finely tune its
      adhesive properties during the colonization of host surfaces, helping cells to
      attach firmly under high shear stress and to detach and spread under low shear
      stress.IMPORTANCEStaphylococcus aureus colonizes the human skin and the nose and
      can cause various disorders, including superficial skin lesions and invasive
      infections. During nasal colonization, the S. aureus surface protein clumping
      factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin,
      but the molecular interactions involved are poorly understood. Here, we unravel
      the molecular mechanism guiding the ClfB-loricrin interaction. We show that the
      ClfB-loricrin bond is remarkably strong, consistent with a high-affinity "dock,
      lock, and latch" binding mechanism. We discover that the ClfB-loricrin
      interaction is enhanced under tensile loading, thus providing evidence that the
      function of an S. aureus surface protein can be activated by physical stress.

PMID- 29208743
TI  - Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell
      Signaling Pathways To Maintain Latent Infection.
AB  - Reactivation of human cytomegalovirus (HCMV) latent infection from early myeloid
      lineage cells constitutes a threat to immunocompromised or immune-suppressed
      individuals. Consequently, understanding the control of latency and reactivation
      to allow targeting and killing of latently infected cells could have far-reaching
      clinical benefits. US28 is one of the few viral genes that is expressed during
      latency and encodes a cell surface G protein-coupled receptor (GPCR), which,
      during lytic infection, is a constitutive cell-signaling activator. Here we now
      show that in monocytes, which are recognized sites of HCMV latency in vivo, US28
      attenuates multiple cell signaling pathways, including mitogen-activated protein
      (MAP) kinase and NF-kappaB, and that this is required to establish a latent
      infection; viruses deleted for US28 initiate a lytic infection in infected
      monocytes. We also show that these monocytes then become potent targets for the
      HCMV-specific host immune response and that latently infected cells treated with
      an inverse agonist of US28 also reactivate lytic infection and similarly become
      immune targets. Consequently, we suggest that the use of inhibitors of US28 could
      be a novel immunotherapeutic strategy to reactivate the latent viral reservoir,
      allowing it to be targeted by preexisting HCMV-specific T cells.IMPORTANCE Human
      cytomegalovirus (HCMV) is a betaherpesvirus and a leading cause of morbidity and
      mortality among immunosuppressed individuals. HCMV can establish latent
      infection, where the viral genome is maintained in an infected cell, without
      production of infectious virus. A number of genes, including US28, are expressed
      by HCMV during latent infection. US28 has been shown to activate many cellular
      signaling pathways during lytic infection, promoting lytic gene expression and
      virus production. As such, the role of US28 remains unclear and seems at odds
      with latency. Here, we show that US28 has the opposite phenotype in cells that
      support latent infection-it attenuates cellular signaling, thereby maintaining
      latency. Inhibition of US28 with a small-molecule inhibitor causes HCMV latent
      infection to reactivate, allowing latently infected cells to be detected and
      killed by the immune system. This approach could be used to treat latent HCMV to
      clear it from human transplants.

PMID- 29208744
TI  - Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive
      Influenza CD8 T-Cell Receptor Repertoires.
AB  - Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear
      how primary infection with this virus leads to massive CD8 T-cell expansion and
      acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in
      severity, from a mild transient influenza-like illness to a prolonged severe
      syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross
      reactive CD8 T-cell response between influenza virus A-M158 (IAV-M1) and EBV
      BMLF1280 (EBV-BM) could modulate the immune response to EBV and play a role in
      determining the severity of AIM in 32 college students. Only ex vivo total IAV-M1
      and IAV-M1+EBV-BM cross-reactive tetramer+ frequencies directly correlated with
      AIM severity and were predictive of severe disease. Expansion of specific cross
      reactive memory IAV-M1 T-cell receptor (TCR) Vbeta repertoires correlated with
      levels of disease severity. There were unique profiles of qualitatively different
      functional responses in the cross-reactive and EBV-specific CD8 T-cell responses
      in each of the three groups studied, severe-AIM patients, mild-AIM patients, and
      seropositive persistently EBV-infected healthy donors, that may result from
      differences in TCR repertoire use. IAV-M1 tetramer+ cells were functionally cross
      reactive in short-term cultures, were associated with the highest disease
      severity in AIM, and displayed enhanced production of gamma interferon, a
      cytokine that greatly amplifies immune responses, thus frequently contributing to
      induction of immunopathology. Altogether, these data link heterologous immunity
      via CD8 T-cell cross-reactivity to CD8 T-cell repertoire selection, function, and
      resultant disease severity in a common and important human infection. In
      particular, it highlights for the first time a direct link between the TCR
      repertoire with pathogenesis and the diversity of outcomes upon pathogen
      encounter.IMPORTANCE The pathogenic impact of immune responses that by chance
      cross-react to unrelated viruses has not been established in human infections.
      Here, we demonstrate that the severity of acute infectious mononucleosis (AIM),
      an Epstein-Barr virus (EBV)-induced disease prevalent in young adults but not
      children, is associated with increased frequencies of T cells cross-reactive to
      EBV and the commonly acquired influenza A virus (IAV). The T-cell receptor (TCR)
      repertoire and functions of these cross-reactive T cells differed between mild-
      and severe-AIM patients, most likely because these two groups of patients had
      selected different memory TCR repertoires in response to IAV infections
      encountered earlier. This heterologous immunity may explain variability in
      disease outcome and why young adults with more-developed IAV-specific memory T
      cell pools have more-severe disease than children, who have less-developed memory
      pools. This study provides a new framework for understanding the role of
      heterologous immunity in human health and disease and highlights an important
      developing field examining the role of T-cell repertoires in the mediation of
      immunopathology.

PMID- 29208745
TI  - The Complex Quorum Sensing Circuitry of Burkholderia thailandensis Is Both
      Hierarchically and Homeostatically Organized.
AB  - The genome of the bacterium Burkholderia thailandensis encodes three complete
      LuxI/LuxR-type quorum sensing (QS) systems: BtaI1/BtaR1 (QS-1), BtaI2/BtaR2 (QS
      2), and BtaI3/BtaR3 (QS-3). The LuxR-type transcriptional regulators BtaR1,
      BtaR2, and BtaR3 modulate the expression of target genes in association with
      various N-acyl-l-homoserine lactones (AHLs) as signaling molecules produced by
      the LuxI-type synthases BtaI1, BtaI2, and BtaI3. We have systematically dissected
      the complex QS circuitry of B. thailandensis strain E264. Direct quantification
      of N-octanoyl-homoserine lactone (C8-HSL), N-3-hydroxy-decanoyl-homoserine
      lactone (3OHC10-HSL), and N-3-hydroxy-octanoyl-homoserine lactone (3OHC8-HSL),
      the primary AHLs produced by this bacterium, was performed by liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the wild-type
      strain and in QS deletion mutants. This was compared to the transcription of
      btaI1, btaI2, and btaI3 using chromosomal mini-CTX-lux transcriptional reporters.
      Furthermore, the levels of expression of btaR1, btaR2, and btaR3 were monitored
      by quantitative reverse transcription-PCR (qRT-PCR). We observed that C8-HSL,
      3OHC10-HSL, and 3OHC8-HSL are differentially produced over time during bacterial
      growth and correlate with the btaI1, btaI2, and btaI3 gene expression profiles,
      revealing a successive activation of the corresponding QS systems. Moreover, the
      transcription of the btaR1, btaR2, and btaR3 genes is modulated by cognate and
      noncognate AHLs, showing that their regulation depends on themselves and on other
      QS systems. We conclude that the three QS systems in B. thailandensis are
      interdependent, suggesting that they cooperate dynamically and function in a
      concerted manner in modulating the expression of QS target genes through a
      successive regulatory network.IMPORTANCE Quorum sensing (QS) is a widespread
      bacterial communication system coordinating the expression of specific genes in a
      cell density-dependent manner and allowing bacteria to synchronize their
      activities and to function as multicellular communities. QS plays a crucial role
      in bacterial pathogenicity by regulating the expression of a wide spectrum of
      virulence/survival factors and is essential to environmental adaptation. The
      results presented here demonstrate that the multiple QS systems coexisting in the
      bacterium Burkholderia thailandensis, which is considered the avirulent version
      of the human pathogen Burkholderia pseudomallei and thus commonly used as an
      alternative study model, are hierarchically and homeostatically organized. We
      found these QS systems to be finely integrated into a complex regulatory network,
      including transcriptional and posttranscriptional interactions, and further
      incorporating growth stages and temporal expression. These results provide a
      unique, comprehensive illustration of a sophisticated QS network and will
      contribute to a better comprehension of the regulatory mechanisms that can be
      involved in the expression of QS-controlled genes, in particular those associated
      with the establishment of host-pathogen interactions and acclimatization to the
      environment.

PMID- 29208746
TI  - Controlled Activity of the Salmonella Invasion-Associated Injectisome Reveals Its
      Intracellular Role in the Cytosolic Population.
AB  - The Salmonella invasion-associated type III secretion system (T3SS1) is an
      essential virulence factor required for entry into nonphagocytic cells and
      consequent uptake into a Salmonella-containing vacuole (SCV). While Salmonella is
      typically regarded as a vacuolar pathogen, a subset of bacteria escape from the
      SCV in epithelial cells and eventually hyperreplicate in the cytosol. T3SS1 is
      downregulated following bacterial entry into mammalian cells, but cytosolic
      Salmonella cells are T3SS1 induced, suggesting prolonged or resurgent activity of
      T3SS1 in this population. In order to investigate the postinternalization
      contributions of T3SS1 to the Salmonella infectious cycle in epithelial cells, we
      bypassed its requirement for bacterial entry by tagging the T3SS1-energizing
      ATPase InvC at the C terminus with peptides that are recognized by bacterial tail
      specific proteases. This caused a dramatic increase in InvC turnover which
      rendered even assembled injectisomes inactive. Bacterial strains conditionally
      expressing these unstable InvC variants were proficient for invasion but
      underwent rapid and sustained intracellular inactivation of T3SS1 activity when
      InvC expression ceased. This allowed us to directly implicate T3SS1 activity in
      cytosolic colonization and bacterial egress. We subsequently identified two T3SS1
      delivered effectors, SopB and SipA, that are required for efficient colonization
      of the epithelial cell cytosol. Overall, our findings support a multifaceted,
      postinvasion role for T3SS1 and its effectors in defining the cytosolic
      population of intracellular SalmonellaIMPORTANCE A needle-like apparatus, the
      type III secretion system (T3SS) injectisome, is absolutely required for
      Salmonella enterica to enter epithelial cells; this requirement has hampered the
      analysis of its postentry contributions. To identify T3SS1-dependent
      intracellular activities, in this study we overcame this limitation by developing
      a conditional inactivation in the T3SS whereby T3SS activity is chemically
      induced during culture in liquid broth, permitting bacterial entry into
      epithelial cells, but is quickly and perpetually inactivated in the absence of
      inducer. In this sense, the mutant acts like wild-type bacteria when
      extracellular and as a T3SS mutant once it enters a host cell. This "conditional"
      mutant allowed us to directly link activity of this T3SS with nascent vacuole
      lysis, cytosolic proliferation, and cellular egress, demonstrating that the
      invasion-associated T3SS also contributes to essential intracellular stages of
      the S. enterica infectious cycle.

PMID- 29208747
TI  - Proposed Role for KaiC-Like ATPases as Major Signal Transduction Hubs in Archaea.
AB  - All organisms must adapt to ever-changing environmental conditions and
      accordingly have evolved diverse signal transduction systems. In bacteria, the
      most abundant networks are built around the two-component signal transduction
      systems that include histidine kinases and receiver domains. In contrast,
      eukaryotic signal transduction is dominated by serine/threonine/tyrosine protein
      kinases. Both of these systems are also found in archaea, but they are not as
      common and diversified as their bacterial and eukaryotic counterparts, suggesting
      the possibility that archaea have evolved other, still uncharacterized signal
      transduction networks. Here we propose a role for KaiC family ATPases, known to
      be key components of the circadian clock in cyanobacteria, in archaeal signal
      transduction. The KaiC family is notably expanded in most archaeal genomes, and
      although most of these ATPases remain poorly characterized, members of the KaiC
      family have been shown to control archaellum assembly and have been found to be a
      stable component of the gas vesicle system in Halobacteria Computational analyses
      described here suggest that KaiC-like ATPases and their homologues with
      inactivated ATPase domains are involved in many other archaeal signal
      transduction pathways and comprise major hubs of complex regulatory networks. We
      predict numerous input and output domains that are linked to KaiC-like proteins,
      including putative homologues of eukaryotic DEATH domains that could function as
      adapters in archaeal signaling networks. We further address the relationships of
      the archaeal family of KaiC homologues to the bona fide KaiC of cyanobacteria and
      implications for the existence of a KaiC-based circadian clock apparatus in
      archaea.IMPORTANCE Little is currently known about signal transduction pathways
      in Archaea Recent studies indicate that KaiC-like ATPases, known as key
      components of the circadian clock apparatus in cyanobacteria, are involved in the
      regulation of archaellum assembly and, likely, type IV pili and the gas vesicle
      system in Archaea We performed comprehensive comparative genomic analyses of the
      KaiC family. A vast protein interaction network was revealed, with KaiC family
      proteins as hubs for numerous input and output components, many of which are
      shared with two-component signal transduction systems. Putative KaiC-based signal
      transduction systems are predicted to regulate the activities of membrane
      associated complexes and individual proteins, such as signal recognition particle
      and membrane transporters, and also could be important for oxidative stress
      response regulation. KaiC-centered signal transduction networks are predicted to
      play major roles in archaeal physiology, and this work is expected to stimulate
      their experimental characterization.

PMID- 29208748
TI  - From Cell Death to Metabolism: Holin-Antiholin Homologues with New Functions.
AB  - Programmed cell death in bacteria is generally triggered by membrane proteins
      with functions analogous to those of bacteriophage holins: they disrupt the
      membrane potential, whereas antiholins antagonize this process. The holin-like
      class of proteins is present in all three domains of life, but their functions
      can be different, depending on the species. Using a series of biochemical and
      genetic approaches, in a recent article in mBio, Charbonnier et al. (mBio
      8:e00976-17, 2017, https://doi.org/10.1128/mBio.00976-17) demonstrate that the
      antiholin homologue in Bacillus subtilis transports pyruvate and is regulated in
      an unconventional way by its substrate molecule. Here, we discuss the connection
      between cell death and metabolism in various bacteria carrying genes encoding
      these holin-antiholin analogues and place the recent study by Charbonnier et al.
      in an evolutionary context.

PMID- 29208750
TI  - Erratum for Sze and Schloss, "Looking for a Signal in the Noise: Revisiting
      Obesity and the Microbiome".

PMID- 29208749
TI  - Development of Anti-Virulence Approaches for Candidiasis via a Novel Series of
      Small-Molecule Inhibitors of Candida albicans Filamentation.
AB  - Candida albicans remains the main etiologic agent of candidiasis, the most common
      fungal infection and now the third most frequent infection in U.S. hospitals. The
      scarcity of antifungal agents and their limited efficacy contribute to the
      unacceptably high morbidity and mortality rates associated with these infections.
      The yeast-to-hypha transition represents the main virulence factor associated
      with the pathogenesis of C. albicans infections. In addition, filamentation is
      pivotal for robust biofilm development, which represents another major virulence
      factor for candidiasis and further complicates treatment. Targeting pathogenic
      mechanisms rather than growth represents an attractive yet clinically unexploited
      approach in the development of novel antifungal agents. Here, we performed large
      scale phenotypic screening assays with 30,000 drug-like small-molecule compounds
      within ChemBridge's DIVERSet chemical library in order to identify small-molecule
      inhibitors of C. albicans filamentation, and our efforts led to the
      identification of a novel series of bioactive compounds with a common biaryl
      amide core structure. The leading compound of this series, N-[3-(allyloxy)
      phenyl]-4-methoxybenzamide, was able to prevent filamentation under all liquid
      and solid medium conditions tested, suggesting that it impacts a common core
      component of the cellular machinery that mediates hypha formation under different
      environmental conditions. In addition to filamentation, this compound also
      inhibited C. albicans biofilm formation. This leading compound also demonstrated
      in vivo activity in clinically relevant murine models of invasive and oral
      candidiasis. Overall, our results indicate that compounds within this series
      represent promising candidates for the development of novel anti-virulence
      approaches to combat C. albicans infections.IMPORTANCE Since fungi are
      eukaryotes, there is a limited number of fungus-specific targets and, as a
      result, the antifungal arsenal is exceedingly small. Furthermore, the efficacy of
      antifungal treatment is compromised by toxicity and development of resistance. As
      a consequence, fungal infections carry high morbidity and mortality rates, and
      there is an urgent but unmet need for novel antifungal agents. One appealing
      strategy for antifungal drug development is to target pathogenetic mechanisms
      associated with infection. In Candida albicans, one of the most common pathogenic
      fungi, morphogenetic transitions between yeast cells and filamentous hyphae
      represent a key virulence factor associated with the ability of fungal cells to
      invade tissues, cause damage, and form biofilms. Here, we describe and
      characterize a novel small-molecule compound capable of inhibiting C. albicans
      filamentation both in vitro and in vivo; as such, this compound represents a
      leading candidate for the development of anti-virulence therapies against
      candidiasis.

PMID- 29208751
TI  - Erratum for Ianiri et al., "FKBP12-Dependent Inhibition of Calcineurin Mediates
      Immunosuppressive Antifungal Drug Action in Malassezia".

PMID- 29208752
TI  - Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent
      Proteome Reveal Pathomechanism-Associated Molecular Signatures.
AB  - Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the
      high volumes of available PD effluent (PDE) represents a rich source of
      biomarkers for monitoring disease and therapy. Although this information could
      help guide the management of PD patients, little is known about the potential of
      PDE to define pathomechanism-associated molecular signatures in PD.We therefore
      subjected PDE to a high-performance multiplex proteomic analysis after depletion
      of highly-abundant plasma proteins and enrichment of low-abundance proteins. A
      combination of label-free and isobaric labeling strategies was applied to PDE
      samples from PD patients (n = 20) treated in an open-label, randomized, two
      period, cross-over clinical trial with standard PD fluid or with a novel PD fluid
      supplemented with alanyl-glutamine (AlaGln).With this workflow we identified 2506
      unique proteins in the PDE proteome, greatly increasing coverage beyond the 171
      previously-reported proteins. The proteins identified range from high abundance
      plasma proteins to low abundance cellular proteins, and are linked to larger
      numbers of biological processes and pathways, some of which are novel for PDE.
      Interestingly, proteins linked to membrane remodeling and fibrosis are
      overrepresented in PDE compared with plasma, whereas the proteins
      underrepresented in PDE suggest decreases in host defense, immune-competence and
      response to stress. Treatment with AlaGln-supplemented PD fluid is associated
      with reduced activity of membrane injury-associated mechanisms and with
      restoration of biological processes involved in stress responses and host
      defense.Our study represents the first application of the PDE proteome in a
      randomized controlled prospective clinical trial of PD. This novel proteomic
      workflow allowed detection of low abundance biomarkers to define pathomechanism
      associated molecular signatures in PD and their alterations by a novel
      therapeutic intervention.

PMID- 29208753
TI  - Compartment-resolved Proteomic Analysis of Mouse Aorta during Atherosclerotic
      Plaque Formation Reveals Osteoclast-specific Protein Expression.
AB  - Atherosclerosis leads to vascular lesions that involve major rearrangements of
      the vascular proteome, especially of the extracellular matrix (ECM). Using single
      aortas from ApoE knock out mice, we quantified formation of plaques by single
      run, high-resolution mass spectrometry (MS)-based proteomics. To probe
      localization on a proteome-wide scale we employed quantitative detergent
      solubility profiling. This compartment- and time-resolved resource of
      atherogenesis comprised 5117 proteins, 182 of which changed their expression
      status in response to vessel maturation and atherosclerotic plaque development.
      In the insoluble ECM proteome, 65 proteins significantly changed, including
      relevant collagens, matrix metalloproteinases and macrophage derived proteins.
      Among novel factors in atherosclerosis, we identified matrilin-2, the collagen IV
      crosslinking enzyme peroxidasin as well as the poorly characterized MAM-domain
      containing 2 (Mamdc2) protein as being up-regulated in the ECM during
      atherogenesis. Intriguingly, three subunits of the osteoclast specific V-ATPase
      complex were strongly increased in mature plaques with an enrichment in
      macrophages thus implying an active de-mineralization function.

PMID- 29208754
TI  - Proactive Use of High-Flow Nasal Cannula With Critically Ill Subjects.
AB  - INTRODUCTION: It has been suggested that use of a high-flow nasal cannula (HFNC)
      could be a first-line therapy for patients with acute hypoxic respiratory
      failure. The purpose of this study was to determine if protocolized use of HFNC
      decreases unplanned intubation and adverse outcomes in an ICU population.
      METHODS: The study was a prospective evaluation of 2 cohorts who received HFNC
      per protocol. Control groups were retrospective selections of subjects who
      received HFNC in the pre-protocol period. Cohort 1 (n = 88) received mechanical
      ventilation for >= 24 h and was extubated directly to HFNC following strict
      protocol criteria. Cohort 2 (n = 83) were placed on HFNC when oxygen requirements
      escalated (>4 L/min). RESULTS: Cohort 1 did not differ from its control group in
      mortality, hospital stay, or ICU days, but there were significant decreases in
      incidence of Gram-negative pulmonary infection (30% vs 9%, P = .001) and use of
      bronchodilator therapy (81% vs 61%, P = .008). Failed extubation rates were
      nearly identical across groups, but time to re-intubation was shorter in the
      protocol group (24 vs 13 h, P = .19). Cohort 2 did not differ significantly from
      its control group in intubation rates or mortality, but subjects managed by
      protocol experienced significant decreases in ICU days (4 vs 3 d, P = .03) and
      hospital days (12 vs 8 d, P = .007). There was a trend toward fewer hours on HFNC
      (33 vs 24 h, P = .10) and faster time to intubation when HFNC failed (19 vs 9 h,
      P = .08). CONCLUSIONS: Extubation to HFNC led to a significant decrease in
      pulmonary infections and bronchodilator therapy in Cohort 1 but did not reduce
      length of stay or rates of failed extubation. When HFNC was used early and per
      protocol (Cohort 2), ICU and hospital lengths of stay were reduced and HFNC was
      initiated more quickly when the need for respiratory support escalated.

PMID- 29208755
TI  - Home Mechanical Ventilation: A 12-Year Population-Based Retrospective Cohort
      Study.
AB  - BACKGROUND: Increasing numbers of individuals are being initiated on home
      mechanical ventilation, including noninvasive (bi-level) and invasive mechanical
      ventilation delivered via tracheostomy due to chronic respiratory failure to
      enable symptom management and promote quality of life. Given the high care needs
      of these individuals, a better understanding of the indications for home
      mechanical ventilation, and health-care utilization is needed. METHODS: We
      performed a retrospective cohort study using provincial health administrative
      data from Ontario, Canada (population ~13,000,000). Home mechanical ventilation
      users were characterized using health administrative data to determine the
      indications for home mechanical ventilation, the need for acute care at the time
      of ventilation approval, and their health service use and mortality rates
      following approval. RESULTS: The annual incidence of home mechanical ventilation
      approval rose from 1.8/100,000 in 2000 to 5.0/100,000 in 2012, or an annual
      increase of approximately 0.3/100,000 persons/y. The leading indications were
      neuromuscular disease, thoracic restriction, and COPD. The indication for the
      remainder could not be determined due to limitations of the administrative
      databases. Of the 4,670 individuals, 23.0% commenced home mechanical ventilation
      following an acute care hospitalization. Among individuals who survived at least
      1 y, fewer required hospitalization in the year that followed home mechanical
      ventilation approval (29.9% vs 39.8%) as compared with the year prior.
      CONCLUSIONS: Utilization of home mechanical ventilation is increasing in Ontario,
      Canada, and further study is needed to clarify the factors contributing to this
      and to further optimize utilization of health-care resources.

PMID- 29208756
TI  - Neurally Adjusted Ventilatory Assist After Pediatric Cardiac Surgery: Clinical
      Experience and Impact on Ventilation Pressures.
AB  - BACKGROUND: After pediatric cardiac surgery, ventilation with high airway
      pressures can be detrimental to right ventricular function and pulmonary blood
      flow. Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator
      interactions, helping maintain spontaneous ventilation. This study reports our
      experience with the use of NAVA in children after a cardiac surgery. We
      hypothesize that using NAVA in this population is feasible and allows for lower
      ventilation pressures. METHODS: We retrospectively studied all children
      ventilated with NAVA (invasively or noninvasively) after undergoing cardiac
      surgery between January 2013 and May 2015 in our pediatric intensive care unit.
      The number and duration of NAVA episodes were described. For the first period of
      invasive NAVA in each subject, detailed clinical and ventilator data in the 4 h
      before and after the start of NAVA were extracted. RESULTS: 33 postoperative
      courses were included in 28 subjects with a median age of 3 [interquartile range
      (IQR) 1-12] months. NAVA was used invasively in 27 courses for a total duration
      of 87 (IQR 15-334) h per course. Peak inspiratory pressures and mean airway
      pressures decreased significantly after the start of NAVA (mean differences of
      5.8 cm H2O (95% CI 4.1-7.5) and 2.0 cm H2O (95% CI 1.2-2.8), respectively, P <
      .001 for both). There was no significant difference in vital signs or blood gas
      values. NAVA was used noninvasively in 14 subjects, over 79 (IQR 25-137) h.
      CONCLUSIONS: NAVA could be used in pediatric subjects after cardiac surgery. The
      significant decrease in airway pressures observed after transition to NAVA could
      have a beneficial impact in this specific population, which should be
      investigated in future interventional studies.

PMID- 29208757
TI  - Critical Velocity Determined by a Non-Exhaustive Method in Subjects With COPD.
AB  - BACKGROUND: Exercise training is an effective and low-cost tool for COPD
      rehabilitation. Thus, validating a non-exhaustive method to determine a patient's
      anaerobic threshold would be a very interesting tool in practical settings. We
      aimed to test the reproducibility of critical velocity values determined in a non
      exhaustive manner (CVNE) and tolerance for exercise performed at this
      physiological marker in subjects with COPD. METHODS: Twelve subjects with COPD
      were evaluated in this cross-sectional study. The study was divided into 2
      phases: Phase A consisted of reproducibility of CVNE for subjects with COPD, and
      Phase B determined the tolerance for exercise tests performed at this
      physiological marker. RESULTS: The proposed protocol for determining CVNE
      presented fair reproducibility according to blood lactate concentrations
      (intraclass correlation coefficient = 0.58). However, we cannot consider that the
      tests were reproducible due to the wide CI (0.03-0.85). Furthermore, moderate and
      strong correlations were observed between the CVNE determined by lactate
      concentration, by oxygen consumption (VO2 ) (r = 0.66), and by heart rate (r =
      0.88). However, a high limit of agreement was observed +/-1.45 km/h and +/-1.55
      km/h, respectively. In the tolerance for exercise test, none of the subjects
      presented lactate destabilization, whereas 3 tests were interrupted by oxygen
      saturation decline and 1 test was interrupted by hemodynamic instability.
      CONCLUSIONS: Although most of the subjects presented good tolerance for exercise
      at CVNE, fair levels of reproducibility were observed in subjects with COPD, even
      using lactate. Thus, the use of CVNE determined through double 3-min efforts
      should be considered with caution.

PMID- 29208758
TI  - Respiratory Volume Monitoring Reduces Hypoventilation and Apnea in Subjects
      Undergoing Procedural Sedation.
AB  - INTRODUCTION: The use of monitored anesthesia care for endoscopic procedures
      increases the risk of respiratory depression, necessitating careful monitoring of
      patient ventilation. We examined the effectiveness of an impedance-based
      respiratory volume monitor (RVM) in improving the safety of patients undergoing
      upper and lower gastrointestinal endoscopies under total intravenous anesthesia.
      We hypothesized that feedback from the RVM would allow anesthesiologists to
      maintain adequate ventilation, which would reduce the duration of respiratory
      depression (ie, hypoventilation and apnea) compared to a blinded control group.
      METHODS: Sixty-five subjects were enrolled in a randomized controlled trial and
      monitored with a noninvasive impedance-based RVM, which displayed respiratory
      traces and calculated expiratory minute ventilation (VE), tidal volume (VT), and
      breathing frequency (f) measurements. Prior to induction of anesthesia, a
      baseline VE measurement (VE-baseline) was taken as a measurement of normal
      breathing. VE was monitored throughout the procedure for signs of hypoventilation
      and apnea. Hypoventilation was defined as VE < 40% VE-baseline, and apneas were
      defined as VE = 0 for > 15 s. RESULTS: Sixty-five subjects were randomly assigned
      to either a control (n = 38) or RVM intervention group (n = 27). Subjects in the
      intervention group had a higher VE% for the entire procedure (P = .045), as well
      as the third and fourth quartile of the procedure compared to the control group
      (P = .01). Likewise, subjects in the RVM intervention group spent significantly
      less time below 40% VE-baseline compared to the control group throughout the
      entire procedure (12 +/- 15% vs 32 +/- 24%, respectively) (P < .001). The median
      number of apneas per subject was greater in the control group (median 2,
      interquartile range 1-2, maximum 4) compared to the RVM intervention group
      (median 1, interquartile range 1-2, maximum 3) (P = .037). CONCLUSIONS: The
      control group had a higher incidence of hypoventilation and apnea compared to the
      RVM intervention group. Respiratory monitoring using the RVM can potentially be a
      useful tool for identifying early signs of respiratory depression and for
      titrating anesthetics to maintain adequate ventilation while minimizing patient
      risk.

PMID- 29208759
TI  - The Role of Multidetector Computed Tomography and the Forced Oscillation
      Technique in Assessing Lung Damage in Adults With Cystic Fibrosis.
AB  - BACKGROUND: With increased survival rates and the consequent emergence of an
      adult population with cystic fibrosis (CF), developing novel tools for periodic
      evaluations of these patients has become a new challenge. Thus, we sought to
      determine the contribution of lung-volume quantification using multidetector
      computed tomography (CT) in adults with CF and to investigate the association
      between structural changes and functional abnormalities. METHODS: This was a
      cross-sectional study in which 21 adults with CF and 22 control subjects
      underwent lung-volume quantification using multidetector CT. Voxel densities were
      divided into 4 bands: -1,000 to -900 Hounsfield units (HU) (hyperaerated region),
      -900 to -500 HU (normally aerated region), -500 to -100 HU (poorly aerated
      region), and -100 to 100 HU (non-aerated region). In addition, all participants
      performed pulmonary function tests including spirometry, body plethysmography,
      diffusion capacity for carbon monoxide, and the forced oscillation technique.
      RESULTS: Adults with CF had more non-aerated regions and poorly aerated regions
      with lung-volume quantification using multidetector CT than controls. Despite
      these abnormalities, total lung volume measured by lung-volume quantification
      using multidetector CT did not differ between subjects and controls. Total lung
      capacity (TLC) measured by body plethysmography correlated with both total lung
      volume (rs = 0.71, P < .001) and total air volume (rs = 0.71, P < .001) as
      measured with lung-volume quantification using multidetector CT. While the
      hyperaerated regions correlated with the functional markers of gas retention in
      the lungs (increased residual volume (RV) and RV/TLC ratio), the poorly aerated
      regions correlated with the resistive parameters measured by the forced
      oscillation technique (increased intercept resistance and mean resistance). We
      also observed a correlation between normally aerated regions and highest
      pulmonary diffusion values (rs = 0.68, P < .001). CONCLUSIONS: In adults with CF,
      lung-volume quantification using multidetector CT can destimate the lung volumes
      of compartments with different densities and determine the aerated and non
      aerated contents of the lungs; furthermore, lung-volume quantification using
      multidetector CT is clearly related to pulmonary function parameters.

PMID- 29208760
TI  - Effectiveness of and overdiagnosis from mammography screening in the Netherlands:
      population based study.
AB  - Objective To analyse stage specific incidence of breast cancer in the Netherlands
      where women have been invited to biennial mammography screening since 1989 (ages
      50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality
      and quantified overdiagnosis.Design Population based study.Setting Mammography
      screening programme, the Netherlands.Participants Dutch women of all ages, 1989
      to 2012.Main outcome measures Stage specific age adjusted incidence of breast
      cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours
      associated with screening were estimated by comparing rates in women aged 50-74
      with those in age groups not invited to screening. Overdiagnosis was estimated
      after subtraction of the lead time cancers. Breast cancer mortality reductions
      and overdiagnosis during 2010-12 were computed without (scenario 1) and with
      (scenario 2) a cohort effect on mortality secular trends.Results The incidence of
      stage 2-4 breast cancers in women aged 50 or more was 168 per 100 000 in 1989 and
      166 per 100 000 in 2012. Screening would be associated with a 5% mortality
      reduction in scenario 1 and with no influence on mortality in scenario 2. In both
      scenarios, improved treatments would be associated with 28% reductions in
      mortality. Overdiagnosis has steadily increased over time with the extension of
      screening to women aged 70-75 and with the introduction of digital mammography.
      After deduction of clinical lead time cancers, 33% of cancers found in women
      invited to screening in 2010-12 and 59% of screen detected cancers would be
      overdiagnosed.Conclusions The Dutch mammography screening programme seems to have
      little impact on the burden of advanced breast cancers, which suggests a marginal
      effect on breast cancer mortality. About half of screen detected breast cancers
      would represent overdiagnosis.

PMID- 29208762
TI  - A dimeric catalytic core relates the short and long forms of ATP
      phosphoribosyltransferase.
AB  - Adenosine triphosphate (ATP) phosphoribosyltransferase (ATP-PRT) catalyses the
      first committed step of histidine biosynthesis in plants and microorganisms. Two
      forms of ATP-PRT have been reported, which differ in their molecular architecture
      and mechanism of allosteric regulation. The short-form ATP-PRT is a hetero
      octamer, with four HisG chains that comprise only the catalytic domains and four
      separate chains of HisZ required for allosteric regulation by histidine. The long
      form ATP-PRT is homo-hexameric, with each chain comprising two catalytic domains
      and a covalently linked regulatory domain that binds histidine as an allosteric
      inhibitor. Here, we describe a truncated long-form ATP-PRT from Campylobacter
      jejuni devoid of its regulatory domain (CjeATP-PRTcore). Results showed that
      CjeATP-PRTcore is dimeric, exhibits attenuated catalytic activity, and is
      insensitive to histidine, indicating that the covalently linked regulatory domain
      plays a role in both catalysis and regulation. Crystal structures were obtained
      for CjeATP-PRTcore in complex with both substrates, and for the first time, the
      complete product of the reaction. These structures reveal the key features of the
      active site and provide insights into how substrates move into position during
      catalysis.

PMID- 29208761
TI  - Priming of innate antimycobacterial immunity by heat-killed Listeria
      monocytogenes induces sterilizing response in the adult zebrafish tuberculosis
      model.
AB  - Mycobacterium tuberculosis remains one of the most problematic infectious agents,
      owing to its highly developed mechanisms to evade host immune responses combined
      with the increasing emergence of antibiotic resistance. Host-directed therapies
      aiming to optimize immune responses to improve bacterial eradication or to limit
      excessive inflammation are a new strategy for the treatment of tuberculosis. In
      this study, we have established a zebrafish-Mycobacterium marinum natural host
      pathogen model system to study induced protective immune responses in
      mycobacterial infection. We show that priming adult zebrafish with heat-killed
      Listeria monocytogenes (HKLm) at 1 day prior to M. marinum infection leads to
      significantly decreased mycobacterial loads in the infected zebrafish. Using rag1
      /- fish, we show that the protective immunity conferred by HKLm priming can be
      induced through innate immunity alone. At 24 h post-infection, HKLm priming leads
      to a significant increase in the expression levels of macrophage-expressed gene 1
      (mpeg1), tumor necrosis factor alpha (tnfa) and nitric oxide synthase 2b (nos2b),
      whereas superoxide dismutase 2 (sod2) expression is downregulated, implying that
      HKLm priming increases the number of macrophages and boosts intracellular killing
      mechanisms. The protective effects of HKLm are abolished when the injected
      material is pretreated with nucleases or proteinase K. Importantly, HKLm priming
      significantly increases the frequency of clearance of M. marinum infection by
      evoking sterilizing immunity (25 vs 3.7%, P=0.0021). In this study, immune
      priming is successfully used to induce sterilizing immunity against mycobacterial
      infection. This model provides a promising new platform for elucidating the
      mechanisms underlying sterilizing immunity and to develop host-directed treatment
      or prevention strategies against tuberculosis.This article has an associated
      First Person interview with the first author of the paper.

PMID- 29208763
TI  - Characterization of the catalytic signature of Scabin toxin, a DNA-targeting ADP
      ribosyltransferase.
AB  - Scabin was previously identified as a novel DNA-targeting mono-ADP
      ribosyltransferase (mART) toxin from the plant pathogen 87.22 strain of
      Streptomyces scabies Scabin is a member of the Pierisin-like subgroup of mART
      toxins, since it targets DNA. An in-depth characterization of both the
      glycohydrolase and transferase enzymatic activities of Scabin was conducted.
      Several protein variants were developed based on an initial Scabin.DNA molecular
      model. Consequently, three residues were deemed important for DNA-binding and
      transferase activity. Trp128 and Trp155 are important for binding the DNA
      substrate and participate in the reaction mechanism, whereas Tyr129 was shown to
      be important only for DNA binding, but was not involved in the reaction
      mechanism. Trp128 and Trp155 are both conserved within the Pierisin-like toxins,
      whereas Tyr129 is a unique substitution within the group. Scabin showed substrate
      specificity toward double-stranded DNA containing a single-base overhang, as a
      model for single-stranded nicked DNA. The crystal structure of Scabin bound to
      NADH - a competitive inhibitor of Scabin - was determined, providing important
      insights into the active-site structure and Michaelis-Menten complex of the
      enzyme. Based on these results, a novel DNA-binding motif is proposed for Scabin
      with substrate and the key residues that may participate in the Scabin.NAD(+)
      complex are highlighted.

PMID- 29208764
TI  - Thiamine and selected thiamine antivitamins - biological activity and methods of
      synthesis.
AB  - Thiamine plays a very important coenzymatic and non-coenzymatic role in the
      regulation of basic metabolism. Thiamine diphosphate is a coenzyme of many
      enzymes, most of which occur in prokaryotes. Pyruvate dehydrogenase and 2
      oxoglutarate dehydrogenase complexes as well as transketolase are the examples of
      thiamine-dependent enzymes present in eukaryotes, including human. Therefore,
      thiamine is considered as drug or diet supplement which can support the treatment
      of many pathologies including neurodegenerative and vascular system diseases. On
      the other hand, thiamine antivitamins, which can interact with thiamine-dependent
      enzymes impeding their native functions, thiamine transport into the cells or a
      thiamine diphosphate synthesis, are good propose to drug design. The development
      of organic chemistry in the last century allowed the synthesis of various
      thiamine antimetabolites such as amprolium, pyrithiamine, oxythiamine, or 3
      deazathiamine. Results of biochemical and theoretical chemistry research show
      that affinity to thiamine diphosphate-dependent enzymes of these synthetic
      molecules exceeds the affinity of native coenzyme. Therefore, some of them have
      already been used in the treatment of coccidiosis (amprolium), other are
      extensively studied as cytostatics in the treatment of cancer or fungal
      infections (oxythiamine and pyrithiamine). This review summarizes the current
      knowledge concerning the synthesis and mechanisms of action of selected thiamine
      antivitamins and indicates the potential of their practical use.

PMID- 29208766
TI  - miR-146a C/G polymorphism increased the risk of head and neck cancer, but overall
      cancer risk: an analysis of 89 studies.
AB  - Several studies have evaluated the association of miR-146a C/G with head and neck
      cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive
      outcomes. To drive a more precise estimation, we carried out this meta-analysis.
      The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane
      Library, and Google Scholar databases to identify eligible studies. A total of 89
      studies were included. The results showed that miR-146a C/G was significantly
      associated with increased HNC risk in dominant model (I2 =15.6%,
      Pheterogeneity=0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002
      1.182, P=0.044). However, no cancer risk was detected under all genetic models.
      By further stratified analysis, we found that rs4919510 mutation contributed to
      the risk of HNC amongst Asians under homozygote model (I2 =0,
      Pheterogeneity=0.541, OR =1.189, 95% CI =1.025-1.378, P=0.022), and dominant
      model (I2 =0, Pheterogeneity=0.959, OR =1.155, 95% CI =1.016-1.312, P=0.028).
      Simultaneously, in the stratified analysis by source of controls, a significantly
      increased cancer risk amongst population-based studies was found under homozygote
      model, dominant model, recessive model, and allele comparison model. However, no
      significant association was found in the stratified analysis by ethnicity and
      source of control. The results indicated that miR-146a C/G polymorphism may
      contribute to the increased HNC susceptibility and could be a promising target to
      forecast cancer risk for clinical practice. However, no significant association
      was found in subgroup analysis by ethnicity and source of control. To further
      confirm these results, well-designed large-scale case-control studies are needed
      in the future.

PMID- 29208765
TI  - Protein arginine methyltransferase expression and activity during myogenesis.
AB  - Despite the emerging importance of protein arginine methyltransferases (PRMTs) in
      regulating skeletal muscle plasticity, PRMT biology during muscle development is
      complex and not completely understood. Therefore, our purpose was to investigate
      PRMT1, -4, and -5 expression and function in skeletal muscle cells during the
      phenotypic remodeling elicited by myogenesis. C2C12 muscle cell maturation,
      assessed during the myoblast (MB) stage, and during days 1, 3, 5, and 7 of
      differentiation, was employed as an in vitro model of myogenesis. We observed
      PRMT-specific patterns of expression and activity during myogenesis. PRMT4 and -5
      gene expression was unchanged, while PRMT1 mRNA and protein content were
      significantly induced. Cellular monomethylarginines (MMAs) and symmetric
      dimethylarginines (SDMAs), indicative of global and type II PRMT activities,
      respectively, remained steady during development, while type I PRMT activity
      indicator asymmetric dimethylarginines (ADMAs) increased through myogenesis.
      Histone 4 arginine 3 (H4R3) and H3R17 contents were elevated coincident with the
      myonuclear accumulation of PRMT1 and -4. Collectively, this suggests that PRMTs
      are methyl donors throughout myogenesis and demonstrate specificity for their
      protein targets. Cells were then treated with TC-E 5003 (TC-E), a selective
      inhibitor of PRMT1 in order to specifically examine the enzymes role during
      myogenic differentiation. TC-E treated cells exhibited decrements in muscle
      differentiation, which were consistent with attenuated mitochondrial biogenesis
      and respiratory function. In summary, the present study increases our
      understanding of PRMT1, -4, and -5 biology during the plasticity of skeletal
      muscle development. Our results provide evidence for a role of PRMT1, via a
      mitochondrially mediated mechanism, in driving the muscle differentiation
      program.

PMID- 29208767
TI  - The feasibility of low-concentration contrast and low tube voltage in computed
      tomography perfusion imaging: an animal study.
AB  - Aim: To investigate the feasibility of low-concentration contrast (270 mg/ml)
      together with low tube voltage (80 kV) and adaptive iterative dose reduction
      (AIDR)-3D reconstruction in liver computed tomography (CT) perfusion
      imaging.Method: A total of 15 healthy New Zealand rabbits received two CT scans
      each. The first scan (control) was acquired at 100 kV and 100 mA with iopromide
      (370 mg/ml), while the second scan (experimental) was acquired at 80 kV and 100
      mA with iodixanol (270 mg/ml) 24 h after the first scan. The obtained images were
      reconstructed with filtered back projection (FBP) and AIDR-3D in the control and
      experimental groups respectively. The perfusion parameters (hepatic artery
      perfusion [HAP], portal vein perfusion [PVP], hepatic perfusion index [HPI], and
      total liver perfusion [TLP]) and image quality (image quality score, average CT
      value of abdomen aorta, signal-to-noise ratio [SNR], contrast-to-noise ratio
      [CNR], and figure of merit [FOM]) were compared using a paired t-test or Mann
      Whitney U test between the two groups, when appropriate. The effective radiation
      dose and iodine intake were also recorded and compared.Results: With the
      exception of the FOM criteria, the image quality and perfusion parameters were
      not significantly different between the two groups. The effective radiation dose
      and iodine intake were 38.79% and 27.03% lower respectively, in the experimental
      group.Conclusion: Low-concentration contrast (iodixanol, 270 mg/ml) together with
      low tube voltage (80 kV) and AIDR-3D reconstruction help to reduce radiation dose
      and iodine intake without compromising perfusion parameters and image quality in
      liver CT perfusion imaging.

PMID- 29208768
TI  - Caspase-independent programmed cell death triggers Ca2PO4 deposition in an in
      vitro model of nephrocalcinosis.
AB  - Nephrocalcinosis involves the deposition of microscopic crystals in the tubular
      lumen or interstitium. While the clinical, biochemical, and genetic aspects of
      the diseases causing nephrocalcinosis have been elucidated, little is known about
      the cellular events in this calcification process. We previously reported a
      phenomenon involving the spontaneous formation of Ca2PO4 nodules in primary
      papillary renal cells from a patient with medullary nephrocalcinosis harboring a
      rare glial cell-derived neurotrophic factor (GDNF) gene variant. We also
      demonstrated that cultivating GDNF-silenced human kidney-2 (HK-2) cells in
      osteogenic conditions for 15 days triggered Ca2PO4 deposits. Given the reportedly
      close relationship between cell death and pathological calcification, aim of the
      present study was to investigate whether apoptosis is involved in the
      calcification of GDNF-silenced HK-2 cells under osteogenic conditions. Silenced
      and control cells were cultured in standard and osteogenic medium for 1, 5, and
      15 days, and any Ca2PO4 deposition was identified by means of von Kossa staining
      and environmental SEM (ESEM) analyses. Based on the results of annexin V and
      propidium iodide (PI) analysis, and terminal deoxynucleotidyl transferase dUTP
      biotin nick end labeling (TUNEL) assay, the silenced cells in the osteogenic
      medium showed a significant increase in the percentage of cells in the late phase
      of apoptosis and an increased Ca2PO4 deposition at 15 days. The results of
      quantitative real-time PCR (qRT-PCR) of BAX and BCL2, and in-cell Western
      analysis of caspases indicated that the cell death process was independent of
      caspase-3, -6, -7, and -9 activation, however. Using this model, we provide
      evidence of caspase-independent cell death triggering the calcification process
      in GDNF-silenced HK-2 cells.

PMID- 29208769
TI  - Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary
      heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy.
AB  - Little is known about the association of the TIMD4 (T-cell immunoglobulin and
      mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and
      lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke
      (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their
      haplotypes and gene-environment interactions on serum lipid levels, the risk of
      CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese
      Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS
      patients were determined by the Snapshot technology. Atorvastatin calcium tablet
      (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after
      genotyping. The rs12522248 genotypic and allelic frequencies were different
      between controls and patients, and were associated with the risk of CHD and IS.
      The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased
      risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C
      C-C haplotype was associated with an increased risk of IS. Variants and their
      haplotypes in controls were associated with triglyceride (rs1501908), low-density
      lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein
      cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to
      HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C);
      rs1501908- and rs12522248-high body mass index (hBMI, >=24 kg/m2; TC); and TIMD4
      HAVCR1 variants-atorvastatin on several lipid parameters were detected.
      Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of
      CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also
      observed. These findings suggest that the TIMD4-HAVCR1 variants may be the
      genetic risk factors for CHD and IS.

PMID- 29208774
TI  - Predicting Relapse with Circulating Tumor DNA Analysis in Lung Cancer.
AB  - <b/> Advances in circulating tumor DNA (ctDNA) analysis are revealing new
      treatment strategies for patients with cancer. Detection of residual disease with
      ctDNA analysis predicts relapse with high accuracy after treatment for early
      stage lung cancer. Cancer Discov; 7(12); 1368-70. (c)2017 AACRSee related article
      by Chaudhuri et al., p. 1394.

PMID- 29208775
TI  - CNS Endothelial Cell Activation Emerges as a Driver of CAR T Cell-Associated
      Neurotoxicity.
AB  - <b/> Central nervous system (CNS) toxicity associated with chimeric antigen
      receptor-based therapeutics has emerged as a significant cause of morbidity and
      mortality, and insights into the pathophysiology of this syndrome have been
      lacking. A new study provides evidence that cytokine-induced CNS endothelial cell
      activation leading to disruption of the blood-brain barrier plays an early and
      critical role in this phenomenon. These insights provide new opportunities for
      targeted therapeutic interventions to modulate endothelial cell activation.
      Cancer Discov; 7(12); 1371-3. (c)2017 AACRSee related article by Gust et al., p.
      1404.

PMID- 29208770
TI  - The role of gut microbiota in the effects of maternal obesity during pregnancy on
      offspring metabolism.
AB  - Obesity is considered a global epidemic. Specifically, obesity during pregnancy
      programs an increased risk of the offspring developing metabolic disorders in
      addition to the adverse effects on the mother per se Large numbers of human and
      animal studies have demonstrated that the gut microbiota plays a pivotal role in
      obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is
      associated with alterations in the composition and diversity of the intestine
      microbial community. Recently, the microbiota in the placenta, amniotic fluid,
      and meconium in healthy gestations has been investigated, and the results
      supported the "in utero colonization hypothesis" and challenged the traditional
      "sterile womb" that has been acknowledged worldwide for more than a century.
      Thus, the offspring microbiota, which is crucial for the immune and metabolic
      function and further health in the offspring, might be established prior to
      birth. As a detrimental intrauterine environment, maternal obesity influences the
      microbial colonization and increases the risk of metabolic diseases in offspring.
      This review discusses the role of the microbiota in the impact of maternal
      obesity during pregnancy on offspring metabolism and further analyzes related
      probiotic or prebiotic interventions to prevent and treat obesity and metabolic
      diseases.

PMID- 29208771
TI  - Advanced iron-overload cardiomyopathy in a genetic murine model is rescued by
      resveratrol therapy.
AB  - Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major
      comorbidity in patients with genetic hemochromatosis and secondary iron overload.
      Therapies are limited in part due to lack of a valid preclinical model, which
      recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin (HJV)
      knockout (HJVKO) mice, which lack HJV, a bone morphogenetic co-receptor protein
      required for hepcidin expression and systemic iron homeostasis, were fed a high
      iron diet starting at 4 weeks of age for a duration of 1 year. Aged HJVKO mice in
      response to iron overload showed increased myocardial iron deposition and
      mortality coupled with oxidative stress and myocardial fibrosis culminating in
      advanced iron-overload cardiomyopathy. In a parallel group, iron-overloaded HJVKO
      mice received resveratrol (240 mg/day) at 9 months of age until 1 year of age.
      Echocardiography and invasive pressure-volume (PV) loop analyses revealed a
      complete normalization of iron-overload mediated diastolic and systolic
      dysfunction in response to resveratrol therapy. In addition, myocardial
      sarcoplasmic reticulum Ca2+ ATPase (SERCa2a) levels were reduced in iron
      overloaded hearts and resveratrol therapy restored SERCa2a levels and suppressed
      up-regulation of the sodium-calcium exchanger (NCX1). Further, iron-mediated
      oxidative stress and myocardial fibrosis were suppressed by resveratrol treatment
      with concomitant activation of the p-Akt and p-AMP-activated protein kinase
      (AMPK) signaling pathways. A combination of ageing and high-iron diet in male
      HJVKO mice results in a valid preclinical model that recapitulates iron-overload
      cardiomyopathy in humans. Resveratrol therapy resulted in normalization of
      cardiac function demonstrating that resveratrol represents a feasible therapeutic
      intervention to reduce the burden of iron-overload cardiomyopathy.

PMID- 29208776
TI  - Losers of Primary Cilia Gain the Benefit of Survival.
AB  - <b/> In this issue, Zhao and colleagues demonstrate that loss of primary cilia in
      medulloblastoma cells confers resistance to the Smoothened (SMO) inhibitor
      sonidegib. When treated with sonidegib, medulloblastoma cells lost their cilia
      and gained resistance. Surprisingly, loss of cilia is associated with recurrent
      mutations in ciliogenesis genes that are eventually able to drive drug
      resistance. These findings uncover a previously unknown mechanism of cancer cells
      in gaining a "persister-like" state against anticancer agents at the expense of
      losing primary cilia. Cancer Discov; 7(12); 1374-5. (c)2017 AACRSee related
      article by Zhao et al., p. 1436.

PMID- 29208780
TI  - Does digestive symptoms require esophago gastroscopy prior to bariatric
      procedure? Assessment of 6 years' experience.
AB  - AIM: Performance of routine preoperative esophagogastroduodenal endoscopy (EGE)
      in patients undergoing bariatric surgery is still a controversial subject. The
      purpose of our study was to evaluate the benefits of performing preoperative EGE
      in a cohort of bariatric patients. MATERIAL AND METHODS: The present
      retrospective study was performed between March 2010 and June 2016. We divided
      the study participants into two groups: group A comprised subjects without
      disturbing upper digestive signs, while group B comprised patients with
      disturbing upper digestive signs. Logistic regression analysis was used to
      identify the pre-dictors that might be associated with abnormal outcomes.
      RESULTS: Our study included 232 patients (who had undergone sleeve gastrectomy,
      gastric bypass, ileal interposition, or transit bipartition). The average age was
      41.4 +/- 10.3 years, and the average body mass index (BMI) was 43.6 +/- 5.1
      kg/m2. Of all the observed gastroscopic abnormalities, the prevalence for
      gastritis (17.3%), followed by esophagitis (10.2%), hiatus hernia (9.4%), and
      bulbitis (8.7%). In multivariate regression analysis, the Gastrointestinal
      Symptom Rating Scale (GSRS) score and upper gastric symptoms were found to be the
      only independent predictive markers (OR = 2.822, 95% CI: 1.674-3.456 and OR
      =2.735, 95% CI: 1.827-3.946, respectively). We identified a positive corre-lation
      between abnormal EGE findings and postoperative complications. CONCLUSION:
      Preoperative EGE had a high rate of detection for the possible abnormalities
      prior to bariatric surgery. Upper gastric symptoms are significant predictive
      factors of postoperative complications. Performing preoperative EGE for
      symptomatic patients could help reduce the morbidity and mortality rates in these
      patients. KEY WORDS: Bariatric surgery, Preoperative endoscopy, Upper digestive
      symptoms.

PMID- 29208781
TI  - Ephebodontics: A Little-known Branch of Dentistry.
AB  - Adolescence is an age group defined from the onset of puberty to establishment of
      social independence. Chronologically it is defined as the age of 10 to 18 years
      but social and behavioral situations may dictate vari-ability.1 Ephebodontics is
      the term coined for adolescent dentistry in the April 1969 issue of Dental
      Clinics of North America. The dental needs of adolescents differ largely from
      other established age groups. There are anomalous physical, emotional, and
      psychological changes in adolescents that need specific health care protocol.2.

PMID- 29208777
TI  - Short Abeta peptides attenuate Abeta42 toxicity in vivo.
AB  - Processing of amyloid-beta (Abeta) precursor protein (APP) by gamma-secretase
      produces multiple species of Abeta: Abeta40, short Abeta peptides (Abeta37-39),
      and longer Abeta peptides (Abeta42-43). gamma-Secretase modulators, a class of
      Alzheimer's disease therapeutics, reduce production of the pathogenic Abeta42 but
      increase the relative abundance of short Abeta peptides. To evaluate the
      pathological relevance of these peptides, we expressed Abeta36-40 and Abeta42-43
      in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory
      effects on Abeta42 toxicity. In contrast to Abeta42, the short Abeta peptides
      were not toxic and, when coexpressed with Abeta42, were protective in a dose
      dependent fashion. In parallel, we explored the effects of recombinant adeno
      associated virus-mediated expression of Abeta38 and Abeta40 in mice. When
      expressed in nontransgenic mice at levels sufficient to drive Abeta42 deposition,
      Abeta38 and Abeta40 did not deposit or cause behavioral alterations. These
      studies indicate that treatments that lower Abeta42 by raising the levels of
      short Abeta peptides could attenuate the toxic effects of Abeta42.

PMID- 29208782
TI  - Relative Translucency of a Multilayered Ultratranslucent Zirconia Material.
AB  - AIM: The aim of this study was to compare the translucency parameter (TP) of
      ultratranslucent multilayered (UTML) zirconia according to thickness and layer
      level. MATERIALS AND METHODS: Rectangles of UTML zirconia with four layers
      [dentin layer (DEL), first transitional layer (FTL), second transitional layer
      (STL), and enamel layer (ENL)] and four different thicknesses (0.4, 0.6, 0.8, and
      1 mm) were milled from blanks. Digital images were taken in a dark studio against
      white and black backgrounds under simulated daylight illumination and
      international commission on illumination (CIE) Lab* color values recorded using
      Photoshop Creative Cloud software. The TP was computed and compared according to
      thickness and layer level using analysis of variance (ANOVA) followed by
      Bonferroni post hoc analysis for multiple comparisons. Significance was set at p
      < 0.05. RESULTS: In each thickness, TP values were similar between any two
      layers. The significant effect of thickness on the TP was observed only in the
      first two layers. In the DEL, translucency was significantly greater at 0.4 mm
      than all other thicknesses. In the FTL, differences were significant between 0.4
      and 0.8 mm and between 0.4 and 1 mm. CONCLUSION: The investigated zirconia does
      not seem to show gradational changes in relative translucency from dentin to
      enamel levels regardless of the thickness used. Thickness affected the TP only in
      the first two layers with better translu-cency at 0.4 mm. CLINICAL SIGNIFICANCE:
      Since relative translucency does not seem to be significantly different between
      layers, clinicians can modify the apicocoronal positioning of the UTML layers
      within the restoration according to the desired Chroma without any implications
      on the clinically perceived translucency. While the thickness of 0.4 mm may be
      suggested for anterior esthetic veneers because of its higher translucency, the
      other thicknesses of 0.6 to 1 mm can be used to mask colored abutments in full
      contour restorations.

PMID- 29208783
TI  - Clinical Time Required and Internal Adaptation in Cavities restored with Bulk
      fill Composites.
AB  - AIM: The aim of this study was to compare the restorative time required and the
      internal adaptation after thermomechanical aging of class I restorations using
      either the conventional incremental technique or bulk-fill technique. MATERIALS
      AND METHODS: Cavities (Class I) were prepared on the occlusal surface of human
      third molars. 40 teeth were divided into four experimental groups according to
      the restorative technique (n = 10): G1 = 3 mm increment of Surefill SDR Flow + 1
      mm Filtek P60; G2 = 3 mm increment of Filtek Bulk-Fill + 1 mm Filtek P60; G3 =
      Filtek P60 inserted with incremental technique; G4 = 3 mm increment of Filtek
      Z350 Flow XT + 1 mm increment of Filtek P60. The required restorative clinical
      time for each technique was marked. Specimens were submitted to thermomechanical
      loading (20,000 mechanical cycles-80 N/thermal cycling-5/55 degrees C for 30
      seconds). After, samples were sectioned, ratio of internal gaps to interface
      length (%) was recorded using dye-staining-gap technique. Data were submitted to
      analysis of variance (ANOVA) and Tukey's test (95% significance). RESULTS: There
      was no significant difference in gap formation and none of the groups was
      completely gap-free. However, a significant reduction on required restorative
      clinical time was observed for G1 (167 +/- 7 seconds), G2 (169 +/- 4 seconds),
      and G4 (169 +/- 8 seconds) when compared with G3 (204 +/- 8 seconds). CONCLUSION:
      No significant difference in gap formation was found among bulk-fill and
      conventional incremental restorative technique tested; however, the use of a bulk
      fill composite reduced 20% of the required restorative clinical time. CLINICAL
      SIGNIFICANCE: None of the restorative techniques applied were able to prevent
      internal gap formation. The use of bulk-fill composite reduced the required
      clinical time to perform class I restorations.

PMID- 29208784
TI  - Impact of Mouthwashes on Antibacterial Activity of Subjects with Fixed
      Orthodontic Appliances: A Randomized Clinical Trial.
AB  - AIM: The study aimed to assess the impact of mouthwashes on antibacterial
      activity of individuals with fixed orthodontic appliances. MATERIALS AND METHODS:
      A total of 60 individuals were considered in the study. Sixty (20 each group)
      nonextraction class I individuals were randomly divided into experimental and
      control groups. Group I: Experimental group [chlorhexidine (CHX) mouthwash],
      group II: Experimental group (neem mouthwash), group III: Control group
      (distilled water). All the clinical examinations were done at baseline and 30th
      day respectively, after the start of orthodontic treatment. The mean differences
      between the different experimental groups were calculated using one-way analysis
      of variance (ANOVA) test. RESULTS: There was no statistical significance at
      baseline mean plaque index (PI), gingival index (GI) scores, and Streptococcus
      mutans (SM) colony count between groups. The PI and GI scores among CHX and neem
      mouthwash groups (p = 0.002, p = 0.032 respectively) were significantly reduced
      after intervention and also the SM colonies count was reduced in CHX and neem
      mouthwash groups and there was significant difference between the groups.
      CONCLUSION: As both mouthwashes showed significant effectiveness on antibacterial
      activity in individuals with fixed orthodontic appliances, neem mouthwash can be
      used as an alternative to CHX. CLINICAL SIGNIFICANCE: It is better to have a
      sound knowledge regarding the use of mouthwash in long term as fixed orthodontics
      are associated with accumulation of SM, enamel demineralization, and an increased
      number of carious lesions, predominantly in sites adjacent to bracket.

PMID- 29208785
TI  - Use of a Partial-thickness Flap for Guided Bone Regeneration in the Upper Jaw.
AB  - INTRODUCTION: Guided bone regeneration (GBR) aims to restore adequate bone volume
      for the placement of implants in an ideal location. In this article, we analyze
      different surgical techniques for tissue management during GBR and a modified
      partial-thickness surgical approach. MATERIALS AND METHODS: In a year's time
      span, five patients were enrolled in the study: Four women and one man (aged 44
      59 years). In four patients, a GBR with simultaneous implant placement was
      adopted, whereas in another patient, a delayed implant placement was done. The
      flap was of full thickness and overturned on the side palatal with the aim of a
      retractor, thus exposing the bone crest. The graft material was covered and
      protected with a resorbable collagen membrane (Geistlich Bio-Gide(r),
      Switzerland). The periosteal layer of the flap was then positioned above the
      resorbable membrane without traction. The sutures as vertical mattress were then
      positioned. Each patient received an intramuscular betamethasone dose (4 mg/50
      kg) and antibiotic therapy for 7 days (amoxicillin + clavulanic acid 1 gm every
      12 hours) and was instructed to maintain oral hygiene and appropriate wound
      cleaning. The patients were recalled at different times to monitor the healing.
      RESULTS: No cases of tissue dehiscence were observed during the period of wound
      healing. One patient, however, showed a delayed exposure 4 months after surgery.
      This occurrence was managed without complications for the patient. CONCLUSION:
      The design of proposed flap seems to be effective in controlling the risk of
      dehiscence during the healing time in the GBR. The vascular supply was rarely
      compromised. The results we obtained are encouraging even if further studies on
      this technique are needed. CLINICAL SIGNIFICANCE: Lateral partial-thickness flaps
      seem to be effective in controlling tissue tension and consequently the risk of
      dehiscence. The incision vestibularly performed should favor the soft tissue
      healing.

PMID- 29208786
TI  - Evaluation of Short and Regular Implants after Prosthesis Placement in the
      Mandible: A Nonrandomized Controlled Clinical Trial.
AB  - AIM: The aim of this nonrandomized controlled preliminary clinical trial was to
      compare treatment using short and conventional implants in the posterior region
      of the mandible after prosthesis installation by means of clinical, resonance
      frequency, and radiographic analyses. MATERIALS AND METHODS: A total of 10
      patients with 40 dental implants already installed were included in this study.
      Four implants were installed for each subject, in which the length of the
      implants (short and conventional) was distributed according to the reminiscent
      alveolar bone in the left and right side of the mandible. All implants received
      splinted prosthesis after the osseointegration period. Analyses were performed
      immediately after prosthesis installation (T1), and 3 (T2) and 6 months (T3)
      after prosthesis placement. RESULTS: The 6-month survival and success rates were
      100% for the short and conventional implants. Probing depths (PDs) after 6 months
      did not show statistical differences between short and conventional implants. All
      groups showed mean implant stability quotient (ISQ) values above 60 in all
      periods evaluated, demonstrating great implant stability, and no differences were
      found between groups at T3. Radiographic measurements showed an increased bone
      loss for conventional implants compared with short implants in all the three
      periods evaluated. CONCLUSION: Our findings suggest that treatment of resorbed
      posterior regions in the mandible with shorter dental implants is as reliable as
      treatment with conventional implants after 6 months of splinted prosthesis
      installation. CLINICAL SIGNIFICANCE: Short implants might be considered a
      predictable treatment alternative to bone augmentation or extensive surgical
      techniques in regions of restricted vertical bone height in the posterior region
      of the mandible.

PMID- 29208787
TI  - Assessment of Marginal Adaptation and Sealing Ability of Root Canal Sealers: An
      in vitro Study.
AB  - AIM: This study aims to compare the marginal adaptation and sealing ability
      [mineral trioxide aggregate (MTA)-Fillapex, AH Plus, Endofill sealers] of root
      canal sealers. MATERIALS AND METHODS: In the present study, the inclusion
      criteria include 45 single-rooted extracted mandibular premolar teeth, with
      single canal and complete root formation. The sectioning of the samples was done
      at the cementoenamel junction using a low-speed diamond disc. Step-back technique
      was used to prepare root canals manually. The MTA-Fillapex, AH Plus, and Endofill
      sealers were the three experimental sealer groups to which 45 teeth were
      distributed. Under scanning electron microscope (SEM), marginal gap at sealer and
      root dentin interface were examined at coronal and apical halves of root canal.
      RESULTS: Among the three maximum marginal adaptations were seen with AH Plus
      sealer (4.10 +/- 0.10) which is followed by Endofill sealer (1.44 +/- 0.18) and
      MTA-Fillapex sealer (0.80 +/- 0.22). Between the coronal and apical marginal
      adaptation, significant statistical difference (p = 0.001) was seen in AH Plus
      sealer. When a Mann-Whitney U-test was done on MTA-Fillapex sealer vs AH Plus
      sealer and AH Plus sealer vs Endofill sealer, there was a statistically
      significant difference (p < 0.05) found between the above two groups at coronal
      and apical third. CONCLUSION: The present study proves that AH Plus sealer has a
      better marginal adaptation when compared with other sealers used. CLINICAL
      SIGNIFICANCE: For sealing space of crown wall and main cone in root canal
      treatment, sealers play an important role. The other advantages of sealers are
      that they are used to fill voids and irregularities in root channel, secondary,
      lateral channels, and space between applied gutta-percha cones and also act as
      tripper during filling.

PMID- 29208788
TI  - Comparative Evaluation of Cleaning Efficacy using Four Novel Nickel-titanium
      Rotary Instruments: An in vitro Scanning Electron Microscope Study.
AB  - AIM: The aim of the study was to compare the cleaning efficacy (debris and smear
      layer removal) of two multifile rotary systems (MTwo and Silk) and two single
      file rotary systems (F6 Skytaper and NeoNiTi). MATERIALS AND METHODS: Eighty
      mesial canals of mandibular first molars were cleaned and shaped using four
      nickel-titanium (NiTi) rotary instruments to size # 25 and 3% NaOCl and 17%
      ethylenediaminetetraacetic acid (EDTA). Samples were randomly divided into four
      equal groups (n = 20) according to instrumentation: Group I, Mtwo; group II,
      Silk; group III, F6 Skytaper; group IV, NeoNiTi. Samples were split
      longitudinally and examined under scanning electron microscope (SEM) for debris
      and smear layer removal in coronal, middle, and apical thirds of each root canal.
      RESULTS: F6 skytaper and Mtwo groups showed significantly higher debris removal
      than Silk and NeoNiTi groups in apical third of root canal as well as when
      compared with NeoNiTi group in middle third. F6 Skytaper group showed
      significantly higher debris and smear layer removal than Silk group in coronal
      third. There was statistically significant difference among all thirds of root
      canal in terms of debris removal in Silk and NeoNiTi groups. There was
      statistically significant difference among all thirds of root canal in F6
      Skytaper and NeoNiTi groups in terms of smear layer removal. CONCLUSION: F6
      Skytaper single-file rotary instrumentation showed the maximum cleaning efficacy
      followed by Mtwo multifile rotary instrumentation in all thirds of root canal.
      CLINICAL SIGNIFICANCE: F6 Skytaper rotary instrument is most efficient followed
      by Mtwo rotary instrument among all rotary instruments.

PMID- 29208789
TI  - General Dental Practitioners as Potential Responders to Disaster Scenario in a
      Highly Disaster-prone Area: An Explorative Study.
AB  - AIM: The aim of this study is to obtain insights pertaining to disaster
      management among Indian general dental practitioners (GDPs). MATERIALS AND
      METHODS: All GDPs in Mangaluru city, Karnataka, India, were included in the
      present study. Their willingness to participate in disaster management and their
      objective knowledge, attitude, behavior, and perceived effectiveness related to
      disaster management were assessed by a structured, pretested, self-administered
      questionnaire. Demographic information was also collected. RESULTS: Overall, 101
      GDPs volunteered for the study, and 96.04% of respondents were willing to
      participate in disaster management. Mean knowledge, attitude, behavior, and
      perceived effectiveness scores were 52.65, 79.60, 41.55, and 64.20% respectively.
      Religion (odds ratio [OR] = -0.194, p = 0.022), marital status (OR = -0.222, p =
      0.040), attachment to college (OR = -0.256, p = 0.037), familiarity with standard
      operating procedures (SOP; OR = -0.502, p = 0.000), and knowledge (OR = 0.265, p
      = 0.003) were significant predictors of behavior. CONCLUSION: The GDPs reported
      knowledge and behavior scores which were low, while their attitude and
      willingness to participate were high. Demographic determinants might be critical
      indicators in disaster management scenario among GDPs. CLINICAL SIGNIFICANCE: The
      present study has crucial implications for policymakers and curriculum changes to
      integrate dentists effectively into disaster response teams. As responsible
      members of the society, the dental fraternity has critical contributions to make
      toward disaster mitigation. Integration of GDPs in a multidisciplinary team
      managing disasters might be crucial, especially in highly disaster-prone areas,
      such as India, with a definite paucity of resources.

PMID- 29208790
TI  - Oral Manifestation in Patients diagnosed with Dermatological Diseases.
AB  - AIM: This study aimed to estimate the frequency of oral lesions in dermatological
      diseased patients attending the outpatient department of Pravara Rural Medical
      and Dental College and Hospital, Pravara Institute of Medical Sciences (Deemed
      University), Loni, Ahmednagar, Maharashtra, India, and the Department of
      Dermatology at Medical College, Ahmednagar, Maharashtra, India. MATERIALS AND
      METHODS: A cross-sectional hospital-based study was conducted in Loni from
      October 2013 to January 2014. A total of 310 patients (mean age 37.2 +/- 16
      years, 61.2% males) completed an oral examination and a personal interview. Oral
      lesions were recorded. Biopsy and smear were used as adjuvant techniques for
      confirmation. Data were analyzed using Statistical Package for the Social
      Sciences (SPSS) (version 15.0.1). RESULTS: Of 310 cases (n = 310) observed for
      skin lesions, 99 cases were psoriasis (31.93%) and 68 cases were lichen planus
      (LP; 21.9%), followed by herpes zoster in 44 cases (14.1%), herpes simplex in 13
      cases (4.1%), pemphigus vulgaris (PV) in 15 cases (4.8%), erythema multiforme
      (EM) in 8 cases (2.5%), bullous pemphigoid (BP) in 4 cases (1.2%), chicken pox in
      3 cases (0.9%), eczema in 52 cases (16.7%), and nutritional deficiency and
      candidiasis in 2 cases (Table 1). CONCLUSION: The dermatologic diseases studied
      frequently occur in the oral cavity. Among them, psoriasis was the most common
      dermatological disease, and LP frequently showed. CLINICAL SIGNIFICANCE: This
      study also depicts that diagnosis and management of these oral lesions should
      also be carried out by oral clinicians so as to improve the oral health
      functioning during the course of the disease. The intraoral examination should be
      incorporated to the routine of dermatologic assistance as the oral manifestations
      can represent preliminary signs or can coexist with the diseases.

PMID- 29208791
TI  - Effect of Temperature on Film Thickness of Two Types of Commonly used Luting
      Cements.
AB  - AIM: The aim of this study is to evaluate the effect of temperature change on
      film thickness of both types of cements. MATERIALS AND METHODS: Totally, 60
      samples were prepared with 10 in each subgroup, thus comprising 30 in each group.
      Materials tested were glass ionomer cement (GIC) type I and zinc phosphate type
      I. Samples were manipulated with manufacturer's instructions and tested according
      to American Dental Association (ADA) guidelines. RESULTS: The mean values of film
      thickness were recorded for both groups I and II. In intragroup comparison of
      group 1, subgroup III (26.560 +/- 0.489 urn) was found to have the highest film
      thickness followed by subgroup II (24.182 +/- 0.576 urn) and the lowest in
      subgroup I (20.209 +/- 0.493 urn). In intragroup comparison of group II, the film
      thickness recorded in subgroup III (25.215 +/- 0.661 urn) was the highest
      followed by subgroup II (21.471 +/- 0.771 urn) and the least in subgroup I
      (17.951 +/- 0.654 urn; p < 0.01). In intergroup comparison of groups I and II,
      group II (21.545 +/- 0.841) was found to have less film thickness than group I
      (23.650 +/- 0.271). The results were found to be statistically significant (p <
      0.01). CONCLUSION: Both zinc phosphate and GICs can be used satisfactorily for
      luting purpose. The temperature fluctuations have a direct influence on the film
      thickness. Zinc phosphate has less film thickness than GIC. CLINICAL
      SIGNIFICANCE: Zinc phosphate should be preferred over GIC in clinical practice,
      and more stress should be given in mechanical preparation of crowns for better
      retentive quality of prosthesis.

PMID- 29208792
TI  - Impact of Educational Intervention for Hand Hygiene on Dental Students'
      Knowledge, Attitude, and Bacterial Contamination Level on Hands.
AB  - AIM: The present study aimed to investigate the impact of the educational
      intervention for hand hygiene (HH) on knowledge, attitude, and mean colony
      forming bacterial counts and type of bacteria on hands of undergraduate dental
      students. MATERIALS AND METHODS: A total of 86 dental students from different
      clinical grades were included in the study. They were divided into two groups,
      group I (55 students) received onetime educational session for HH at the start of
      the academic year and group II (31 students) received an extra reenforce-ment
      session 6 months later. After 2 weeks of reenforcement session, a self
      administrated questionnaire was directed to all participants assessing their
      knowledge and attitude about HH. Fingertip prints of the five fingers of the
      dominant hand from every participant were pressed onto blood agar plates in
      triplets at the same clinical session, before and after HH. Bacterial colony
      forming units (CFUs) on each plate were recorded and identified
      microbiologically. RESULTS: The overall scores of knowledge and attitude showed
      higher levels in group II than in group I with nonsignificant differences between
      both groups as regards knowledge and significant differences (p < 0.05) as
      regards attitude. Mean CFUs showed extremely significant differences (p < 0.000)
      between 2nd and 3rd counts and between 1st and 2nd counts except for students of
      group I where the difference was only significant (p < 0.05). Normal bacterial
      flora was identified in 94.9% of the plates (92.2% coagulase-negative
      Staphylococci and 2.7% Micrococcus). Potentially pathogenic bacteria isolated
      from the other plates were Klebsiella pneumonia, Pseudomonas spp., and spore
      forming aerobic nonhemolytic Bacilli. CONCLUSION: Reenforcement session had a
      positive impact on HH knowledge, attitude, and reduction of bacterial CFUs.
      CLINICAL SIGNIFICANCE: Continuous education with frequent training sessions is
      recommended to reinforce HH compliance and reduce cross-contamination.

PMID- 29208793
TI  - Assessment of Proliferative Potential of Odontogenic Keratocyst and Dentigerous
      Cyst using Podoplanin: An Immunohistochemical Study.
AB  - INTRODUCTION: Odontogenic cysts are commonly encountered lesions among head and
      neck pathologies. Odontogenic keratocyst (OKC) has unique features of recurrence
      and local aggressiveness. Podoplanin (PDP) is a lymphatic endothelial marker and
      is shown to be expressed in a variety of tissues. Hence, we planned to assess the
      significance of PDP in OKC and dentigerous cyst (DC). MATERIALS AND METHODS: The
      present study included assessment of immunoexpression of PDP in OKC and DC.
      Twenty specimens each of OKC and DC were included in the present study and were
      stained with D2-40 antibody. All the sections were analyzed and were categorized
      as negative staining, weakly positive staining, and strongly positive staining.
      All the results were analyzed by Statistical Package for the Social Sciences
      (SPSS) software. RESULTS: We detected PDP-positive staining in the cell membrane
      and cytoplasm of the cells of basal cell layer and supra-basal cell layers. In DC
      cases, we observed positive staining only in cases associated with inflammation.
      CONCLUSION: Podoplanin does play a significant role in enhancing the local
      invasive and neoplastic properties of OKC. CLINICAL SIGNIFICANCE: Podoplanin
      expression in OKC is potentially associated with moderate invasive nature of the
      neighboring structures.

PMID- 29208794
TI  - Intricate Estimation and Assessment of Surface Conditioning of Posts to improve
      Interfacial Adhesion in Post-core Restorations: An in vitro Study.
AB  - INTRODUCTION: Post and core restorations are routinely used for restoring grossly
      decayed tooth structures. Various chemical agents are known to affect the
      interfacial adhesions between the post and the core. Hence, we planned the
      present study to evaluate the effect of various post-surface treatments on the
      interfacial strength between the posts and composite materials that are used for
      building up the core portion. MATERIALS AND METHODS: The present study included
      assessment of the effect of surface conditioning of posts on the interfacial
      adhesion in post-core restorations. A total of 80 clear post-tapers were included
      and were divided broadly into four study groups based on the type of chemical
      testing protocols used. Various chemical treatments included alkaline potassium
      permanganate, hydrogen peroxide, and phosphoric acid. The fourth group was the
      control group. The composite core material was used for building up the core.
      Testing of the tensile load was done on a universal testing machine. All the
      results were analyzed by the Statistical Package for the Social Sciences (SPSS)
      software. RESULTS: The highest bond strength was observed in the study group
      treated with alkaline potassium permanganate, while the lowest was observed in
      the control group followed by the hydrogen peroxide group. While comparing the
      mean bond strength in between various study groups, significant results were
      obtained. CONCLUSION: Chemical treatment protocol significantly alters the mean
      bond strength of the post and core restoration. CLINICAL SIGNIFICANCE: Potassium
      permanganate significantly increases the bond strength between the fiber post and
      core restoration.

PMID- 29208795
TI  - In vitro Assessment of Influence of Various Bleaching Protocols on the Strength
      of Ceramic Orthodontic Brackets bonded to Bleached Tooth Surface: A Comparative
      Study.
AB  - INTRODUCTION: Esthetics is one of the common issues because of which patients
      consult dental orthodontic treatment. Two ways of tooth bleaching are available
      these days, which includes in-office bleach and home bleach. Various bleaching
      protocols are available these days for treating the tooth surfaces. Hence, we
      planned the present study for investigating the impact of various intracoronal
      bleaching protocols on shear bond strength of ceramic brackets bonded to tooth
      surface after bleaching. MATERIALS AND METHODS: The present study included
      assessment of 100 extracted maxillary central incisors with the integrated buccal
      surface. A resin block was made and individual teeth were embedded in each block.
      Root canal therapy procedure was performed in all the teeth, after which 2 mm
      short of tooth apex up to the level of cementoenamel junction, removal of the
      root canal filling was done. All the samples were broadly divided into four study
      groups with 25 samples in each group. Bleaching procedure was carried in all the
      samples intracoronally followed by testing of shear bond strength using universal
      force testing machine. Following the modified adhesive remnant index (AI),
      assessment of remaining adhesive on the brackets was done. All the results were
      compiled and analyzed by Statistical Package for the Social Sciences (SPSS)
      software version 17.0. RESULTS: In the control group, mean shear bond strength
      was found to be 17.9 MPa. While comparing the carbamide peroxide (CP) group with
      sodium perborate study group, we observed a statistically significant difference.
      Nonsignificant results were obtained while comparing the shear bond strength in
      between sodium perborate group and hydrogen peroxide (HP) group. CONCLUSION:
      Intracoronal bleaching does affect the shear bond strength of ceramic brackets.
      Sodium perborate bleaching influences shear bond strength more strongly than
      other bleaching agents such as CP and HP. CLINICAL SIGNIFICANCE: In patients
      undergoing orthodontic treatment, HP is a preferred agent where bleaching has to
      be followed by orthodontic bonding to the tooth surface.

PMID- 29208796
TI  - Comparative Evaluation of Tensile Strength in Die Stone Incorporated with Sodium
      and Calcium Hypochlorite as Disinfectants: An in vitro Study.
AB  - AIM: The aim of this study was to evaluate the tensile strength of die stone
      incorporated with sodium and calcium hypochlorite as disinfectants. MATERIALS AND
      METHODS: Two commercially available type IV die stone (Kalrock: Kalabhai Karson
      Pvt., Ltd and Pearlstone: Asian Chemicals) and two commercially available
      disinfectant solutions (sodium hypochlorite and calcium hypochlorite: Beachem
      Laboratory Chemical Private Limited, Chennai and Leo Chem Private Limited,
      Bengaluru) were used in this study, and the tensile strength was measured using
      Lloyd's Universal Testing Machine. RESULTS: The results show that incorporating
      the disinfecting solutions decreases the tensile strength of both products. The
      effect of decreasing tensile strength on type IV gypsum product is seen more in
      calcium hypochlorite when compared with sodium hypochlorite disinfecting
      solution, and the tensile strength of Kalrock specimens is higher than Pearlstone
      specimens after disinfecting with sodium hypochlorite and calcium hypochlorite
      solution. The statistical results also show significant results in all the groups
      when compared with the control group. CONCLUSION: The incorporation of sodium and
      calcium hypochlorite disinfecting solutions is not an encouraging method for both
      die materials as it reduces the tensile strength of type IV gypsum product.
      Tensile strength of Kalstone(r) die material is superior than Pearlstone(r) die
      material after mixing with sodium hypochlorite and calcium hypochlorite. CLINICAL
      SIGNIFICANCE: According to the recommendations of Americans with Disability Act
      (ADA) and the Centers for Disease Control and Prevention, disinfecting the whole
      cast without or minimal changes in physical and mechanical properties was the
      motto of the study. The tensile strength in type IV gypsum product plays a most
      important role in retrieval of cast from impression, especially in narrow tooth
      preparation. This study reveals that incorporating method of disinfecting
      solutions is not recommended as it reduces the tensile strength.

PMID- 29208797
TI  - Caries Preventive Effect of Sodium Fluoride Varnish on Deciduous Dentition: A
      Clinical Trial.
AB  - AIM: The aim of the study is to evaluate the efficacy of intensive application of
      sodium fluoride varnish in reducing caries incidence among children aged 6 to 7
      years. MATERIALS AND METHODS: The study was a randomized controlled trial
      conducted among 6- to 7-year-old children of Sangamner, Maharashtra, India.
      Nearly 200 randomly selected children were randomized into two groups: Control
      group and intervention (varnish) group. Dental examination to record the caries
      experiences was conducted at baseline and at 1-year follow-up. The fluoride
      varnish was applied for three times in a week for a period of 1 year. Mean
      decayed, missed, and filled teeth (DMFT) were compared between and within groups
      using t-test. RESULTS: Out of 200 participants, there were 3 dropouts for control
      group and 4 for intervention group. Nearly 55% study participants were males and
      remaining were females. There was a statistically significant difference between
      the baseline and follow-up caries levels in varnish group for deciduous
      dentition. Mean caries reduction in this study was 26%. CONCLUSION: After 1 year
      of study, we found significant caries reversal in deciduous dentition among the 6
      to 7-year-olds after intensive fluoride application. Such a regimen can be
      advocated to encourage the practitioners and the caregivers alike for early
      caries prevention. CLINICAL SIGNIFICANCE: Intensive fluoride application (three
      times a week) once a year was found to be effective in reducing the incidence of
      detectable carious lesions and can be advocated to the dental professionals to be
      incorporated in their routine preventive clinical practice.

PMID- 29208798
TI  - A Clinical and Microbiological Evaluation of Helicobacter pylori in Recurrent
      Aphthous Stomatitis.
AB  - AIM: The aim of this study is to evaluate the association of Helicobacter pylori
      in recurrent aphthous stomatitis (RAS) with or without peptic ulcer. MATERIALS
      AND METHODS: A total of 42 patients were selected for the present study from
      outpatient Department of Oral Medicine, and divided into control (group I) and
      test groups (groups II, III). A total number of 15 patients suffering from RAS
      based on history and clinical examination was selected as group II. A total
      number of 12 patients suffering concomitantly from RAS and duodenal ulcer based
      on history and clinical examination were selected as group III. A total number of
      15 healthy subjects were selected as controls in group I. All selected subjects
      belonged to the age group of 16 to 45 years. Data were tabulated and
      statistically analyzed with Statistical Package for the Social Sciences (SPSS)
      statistical software version 19 of IBM, Chicago, Illinois, USA. RESULTS: Among
      all three groups, 54.8% was negative and 45.2% was positive for H. pylori. No
      significant relation was established between H. pylori and RAS. CONCLUSION: In
      the present study, there was no association of H. pylori in patients with RAS and
      in patients with RAS along with gastric ulcers. CLINICAL SIGNIFICANCE: This
      clinical study evaluated the relation of H. pylori in RAS patients.

PMID- 29208799
TI  - An Alternative Approach for Space Opening in a Bilateral Maxillary Lateral
      Incisor Agenesis Patient using Miniplates.
AB  - AIM: This case report aimed to present an orthodontic mechanic alternative for
      space opening in a patient missing maxillary lateral incisors, using miniplates
      as anchorage, associated with self-ligating brackets. BACKGROUND: Dental agenesis
      affects the population causing esthetic and functional damages. The prevalence of
      missing maxillary lateral incisors should be considered for its significant rate
      and negative impact on smile esthetics. CASE REPORT: This treatment was chosen
      based on the presence of balanced facial pattern, large canine anatomy, the need
      to improve dental occlusion to prevent further wear, and patient's esthetic
      complaint. To obtain the results, upper third molars were extracted, and two
      miniplates were installed to distalize the upper arch with no need for patient
      compliance or auxiliary devices. Self-ligating brackets were used to reduce
      friction on posterior teeth, thus facilitating movement with light force
      application. At the end of 19 months, the patient presented with class I good
      overbite and overjet, and adequate space for implant and prosthetics; also, good
      facial esthetic was maintained. CONCLUSION: When indicated, space opening may
      provide excellent esthetics and functional results, and even more predictable
      results when skeletal anchorage miniplates are used to distalize all posterior
      teeth. CLINICAL SIGNIFICANCE: Considering the high level of esthetic and
      functional compromise caused by dental agenesis, the technique hereby described
      represents a viable mechanic alternative within orthodontic possibilities.

PMID- 29208800
TI  - Spanning the Horizon of Accuracy of Different Intraoral Radiographic Modalities:
      A Systematic Review.
AB  - AIM: This study was conducted with an aim to systematically review the literature
      for assessing the accuracy of intraoral radiographs in detection of dental
      caries. INTRODUCTION: Despite the advancements in oral disease science, dental
      caries continues to be a worldwide health concern, affecting humans of all ages.
      Correct diagnosis of caries is critical both in clinical practice as well as in
      epidemiology and radiography are worthwhile adjunct for a thorough examination.
      RESULTS: A literature review was performed in PubMed Central and Cochrane
      library, Embase, and Google Scholar, and these databases were searched up to
      2016. The primary outcome measure was to assess the accuracy of intraoral
      radiographs in the detection of dental caries based on sensitivity and
      specificity. The sensitivity for conventional radiographs for the detection of
      lesions in enamel (16-68%) and dentin (16-96%) was found to be superior as
      compared with other modalities of digital radiography, whereas the specificity of
      digital radiography was found to be superior in detection of lesion in enamel (77
      96%) and dentin (84-100%) when compared with conventional radiography.
      Sensitivity of conventional radiographs was noted to be superior as compared with
      digital radiography, whereas in terms of specificity, digital was found to be
      superior to conventional radiographs. CONCLUSION: Although there was no
      significant difference between digital and conventional radiography in the
      diagnosis of caries, conventional radiographs were able to detect carious lesion,
      in general, but for lesion to be detected precisely, digital was found to be
      superior. CLINICAL SIGNIFICANCE: As digital radiography produces lower ionizing
      radiation, dental professionals should employ this method in their routine dental
      practice for diagnosing and treating carious lesions.

PMID- 29208801
TI  - Grossing of Oral Pathologies-Revisited.
AB  - Grossing pathologies, otherwise known as macroscopic cutup for diagnostic
      information, is a vital laboratory step as it impacts the patient treatment and
      prognosis. However, it is a challenging skill acquired with keen observation,
      experience, and correlation between macroscopy and microscopy. Before we make an
      attempt to gross, it is imperative to have sound knowledge about its general
      principles and its applications as it differs among different lesions. Thereby,
      we have made an attempt to enhance the guidelines for gross description and also
      updated on the general principles. A practical insight has been provided with
      respect to grossing of oral mucosal biopsies, pathology of malignancies,
      odontogenic cysts, cystic odontogenic tumors, salivary gland pathologies, and
      lymph nodes along with the brief history of gross pathology.

PMID- 29208802
TI  - Eliminating cataract blindness: Are we on target?

PMID- 29208803
TI  - Cataract surgery: The journey thus far.

PMID- 29208804
TI  - Cataract surgery and controversy: Susruta-Daviel-Kelman.

PMID- 29208805
TI  - Endophthalmitis prophylaxis in cataract surgery.

PMID- 29208806
TI  - Cataract surgery training during ophthalmology residency in India: Challenges and
      how to overcome them?

PMID- 29208807
TI  - Review of manual small-incision cataract surgery.
AB  - Cataract surgery has undergone many changes with the size of incision
      progressively decreasing over time with an incision of 12.0 mm for intracapsular
      cataract extraction to 2.2-2.8 mm in phacoemulsification. However,
      phacoemulsification due to high cost and equipment maintenance cannot be employed
      widely in developing countries. Manual small-incision cataract surgery (MSICS)
      offers similar advantages with the merits of wider applicability, less time
      consuming, a shorter learning curve, and lower cost. MSICS can be performed in
      high-volume setups due to fast technique. Here, we review the various techniques,
      safety and efficacy of MSICS, and its progress and utility in developing and
      underdeveloped countries.

PMID- 29208808
TI  - Intraocular lens calculations in atypical eyes.
AB  - Cataract surgery is the most performed surgical procedure in the field of
      ophthalmology. The process of intraocular lens (IOL) calculations is a critical
      step to achieving successful outcomes. Many IOL formulae exist to guide surgeons
      through the difficult process of picking the most appropriate lens to achieve a
      certain target refraction. However, these formulae reach within 0.50 diopters of
      the target refraction only 75% of the time, leaving 25% of the eyes with a
      significant refractive surprise. A literature review was performed to investigate
      all the relevant published material on the history, progress, and recent
      advancements of IOL calculations. Based on this review, the appropriate history,
      evolution, progress, limitations, and recent advancements are analyzed and
      explained. Although the modern IOL formulae and biometric devices perform well
      for average eyes, they are suboptimal for eyes with atypical biometric parameters
      and also those that are postrefractive and keratoconic. There has not been a
      single, perfect formula that can resolve the complexities of this process.
      Various methods of formula optimization and newer generation of IOL formulae and
      devices may hold the key to improving outcomes in both typical and atypical eyes.
      These solutions minimize refractive error by introducing new input parameters and
      complex mathematical techniques to better estimate postoperative lens position.

PMID- 29208809
TI  - Optimizing outcomes with multifocal intraocular lenses.
AB  - Modern day cataract surgery is evolving from a visual restorative to a refractive
      procedure. The advent of multifocal intraocular lenses (MFIOLs) allows greater
      spectacle independence and increased quality of life postoperatively. Since the
      inception in 1980s, MFIOLs have undergone various technical advancements
      including trifocal and extended depth of vision implants more recently. A
      thorough preoperative workup including the patients' visual needs and inherent
      ocular anatomy allows us to achieve superior outcomes. This review offers a
      comprehensive overview of the various types of MFIOLs and principles of
      optimizing outcomes through a comprehensive preoperative screening and management
      of postoperative complications.

PMID- 29208810
TI  - Optimizing outcomes with toric intraocular lenses.
AB  - Toric intraocular lenses (IOLs) are the procedure of choice to correct corneal
      astigmatism of 1 D or more in cases undergoing cataract surgery. Comprehensive
      literature search was performed in MEDLINE using "toric intraocular lenses,"
      "astigmatism," and "cataract surgery" as keywords. The outcomes after toric IOL
      implantation are influenced by numerous factors, right from the preoperative case
      selection and investigations to accurate intraoperative alignment and
      postoperative care. Enhanced accuracy of keratometry estimation may be achieved
      by taking multiple measurements and employing at least two separate devices based
      on different principles. The importance of posterior corneal curvature is
      increasingly being recognized in various studies, and newer investigative
      modalities that account for both the anterior and posterior corneal power are
      becoming the standard of care. An ideal IOL power calculation formula should take
      into account the surgically induced astigmatism, the posterior corneal curvature
      as well as the effective lens position. Conventional manual marking has given way
      to image-guided systems and intraoperative aberrometry, which provide a mark-less
      IOL alignment and also aid in planning the incisions, capsulorhexis size, and
      optimal IOL centration. Postoperative toric IOL misalignment is the major factor
      responsible for suboptimal visual outcomes after toric IOL implantation.
      Realignment of the toric IOL is needed in 0.65%-3.3% cases, with more than 10
      degrees  of rotation from the target axis. Newer toric IOLs have enhanced
      rotational stability and provide precise visual outcomes with minimal higher
      order aberrations.

PMID- 29208811
TI  - Reviewing the visual benefits of femtosecond laser-assisted cataract surgery: Can
      we improve our outcomes?
AB  - Femtosecond laser-assisted cataract surgery (FLACS) was introduced in 2009 and
      has increasingly been incorporated into surgical practice. The automation of
      three key aspects of cataract surgery was expected to deliver a significant
      improvement in both refractive and safety outcomes. The published literature has
      not yet shown consistent refractive improvement above conventional techniques.
      The purpose of this paper is to review current FLACS refractive outcomes and
      explore factors that may have contributed to the current findings and whether
      future improvements are possible.

PMID- 29208812
TI  - Cataract surgery in small pupils.
AB  - This paper presents the review of historical aspects and the current state-of-the
      art in various pupil dilatation methods to be used in cataract surgery. The
      surgical algorithm in managing small pupil cases should include topical and
      intraocular mydriatics, appropriately selected viscosurgical device and
      mechanical dilatation with instruments, iris hooks, and/or pupil expanders.

PMID- 29208813
TI  - Decision-making and management of uveitic cataract.
AB  - The visual outcome of uveitic cataract surgery depends on the underlying uveitic
      diagnosis, the presence of vision-limiting pathology and perioperative
      optimization of disease control. A comprehensive preoperative ophthalmic
      assessment for the presence of concomitant ocular pathology, with particular
      emphasis on macula and optic nerve involvement, is essential to determine which
      patients will benefit from improved vision after cataract surgery. Meticulous
      examination in conjunction with adjunct investigations can help in preoperative
      surgical planning and in determining the need for combined or staged procedures.
      The eye should be quiescent for a minimum of 3 months before cataract surgery.
      Perioperative corticosteroid prophylaxis is important to reduce the risk of
      cystoid macular edema and recurrence of the uveitis. Antimicrobial prophylaxis
      may also reduce the risk of reactivation in eyes with infectious uveitis. Uveitic
      cataracts may be surgically demanding due to the presence of synechiae,
      membranes, and pupil abnormalities that limit access to the cataract. This can be
      overcome by manual stretching, multiple sphincterotomies or mechanical dilation
      with pupil dilation devices. In patients <2 years of age and in eyes where the
      inflammation is poorly controlled, intraocular lens implantation should be
      deferred. Intensive local and/or oral steroid prophylaxis should be given
      postoperatively if indicated. Patients must be monitored closely for disease
      recurrence, excessive inflammation, raised intraocular pressure, hypotony, and
      other complications. Complications must be treated aggressively to improve visual
      rehabilitation. With proper patient selection, improved surgical techniques and
      optimization of peri- and post-operative care, patients with uveitic cataracts
      can achieve good visual outcomes.

PMID- 29208814
TI  - Pediatric cataract.
AB  - Pediatric cataract is a leading cause of childhood blindness. Untreated cataracts
      in children lead to tremendous social, economical, and emotional burden to the
      child, family, and society. Blindness related to pediatric cataract can be
      treated with early identification and appropriate management. Most cases are
      diagnosed on routine screening whereas some may be diagnosed after the parents
      have noticed leukocoria or strabismus. Etiology of pediatric cataract is varied
      and diagnosis of specific etiology aids in prognostication and effective
      management. Pediatric cataract surgery has evolved over years, and with improving
      knowledge of myopic shift and axial length growth, outcomes of these patients
      have become more predictable. Favorable outcomes depend not only on effective
      surgery, but also on meticulous postoperative care and visual rehabilitation.
      Hence, it is the combined effort of parents, surgeons, anesthesiologists,
      pediatricians, and optometrists that can make all the difference.

PMID- 29208815
TI  - Managing the posterior polar cataract: An update.
AB  - Posterior polar cataracts (PPC) have always been a challenge for cataract
      surgeons due to their inherently higher propensity for posterior capsule rupture.
      Over the years, several technical modifications have been suggested to enhance
      safety and reduce posterior capsule rupture rates in these polar cataracts. This
      review article tries to present the various techniques and strategies to
      published in literature to manage PPCs. It also discusses pearls for making
      surgery more reproducible and consistent, as well as the role of newer diagnostic
      and surgical technology based on the published literature on the subject.

PMID- 29208816
TI  - Posterior capsular rent: Prevention and management.
AB  - This review article deals with a potentially sight threatening complication -
      rupture of the posterior capsule - during cataract surgery. Cataract surgery is
      the most commonly performed surgical procedure in ophthalmology and despite
      tremendous technical and technological advancements, posterior capsular rent
      (PCR) still occurs. PCR occurs both in the hands of experienced senior surgeons
      and the neophyte surgeons, although with a higher frequency in the latter group.
      Additionally, certain types of cataracts are prone to this development. If
      managed properly in a timely manner the eventual outcome may be no different from
      that of an uncomplicated case. However, improper management may lead to serious
      complications with a higher incidence of permanent visual disability. The article
      covers the management of posterior capsular rent from two perspectives: 1.
      Identifying patients at higher risk and measures to manage such patients by
      surgical discipline, and 2. Intraoperative management of posterior capsular rent
      and various case scenarios to minimize long-term complications.This review is
      written for experienced and not-so-experienced eye surgeons alike to understand
      and manage PCR.

PMID- 29208817
TI  - Glued intrascleral haptic fixation of an intraocular lens.
AB  - Glued intrascleral haptic fixation of an intraocular lens (glued IOL) has evolved
      as a technique with various modifications that are adopted and practiced by
      several surgeons. With adequate and appropriate haptic tuck, glued IOL imparts a
      stable IOL fixation and is a secured method of secondary IOL placement with no
      pseudophacodonesis.

PMID- 29208818
TI  - Corneal edema after phacoemulsification.
AB  - Phacoemulsification is the most commonly performed cataract surgery in this era.
      With all the recent advances in investigations and management of cataract through
      phacoemulsification, most of the patients are able to achieve excellent visual
      outcome. Corneal edema after phacoemulsification in the immediate postoperative
      period often leads to patient dissatisfaction and worsening of outcome. Delayed
      onset corneal edema often warrants endothelial keratoplasty. This review
      highlights the etiopathogenesis, risk factors, and management of corneal edema in
      the acute phase including descemet's membrane detachment (DMD) and toxic anterior
      segment syndrome. Various investigative modalities such as pachymetry, specular
      microscopy, anterior segment optical coherence tomography, and confocal
      microscopy have been discussed briefly.

PMID- 29208819
TI  - Antibiotic prophylaxis in cataract surgery - An evidence-based approach.
AB  - Various protocols are being followed for endophthalmitis prophylaxis in cataract
      surgery, and this subject continues to be a matter of debate. We summarize the
      most recent evidence-based studies on this topic with additional stress on
      intracameral (IC) antibiotic prophylaxis. Here, we discuss several large,
      international clinical studies which discuss the efficacy, adoption, safety,
      cost, and newer trends in antibiotic prophylaxis. Majority of these studies
      report a significant reduction in endophthalmitis rates with IC antibiotic
      prophylaxis. Efficacy data have been reported for IC cefuroxime, vancomycin, and
      moxifloxacin. Surgeons are now looking for alternatives to vancomycin for IC
      prophylaxis because of its association with the rare but sight-threatening
      complication of hemorrhagic occlusive retinal vasculitis. A recent large clinical
      study shows convincing efficacy with IC moxifloxacin prophylaxis. Two large
      studies have also reported significant endophthalmitis reduction following use of
      IC antibiotic prophylaxis, in eyes with posterior capsule tear which are at
      highest risk for infection. Except for one randomized controlled trial, there is
      a lack of prospective data on this subject; however, considering the complexity
      of performing such studies, surgeons have to rely on the mounting evidence from
      other recent big data studies. Availability of approved intraocular antibiotic
      formulations will see a much higher adoption in the future.

PMID- 29208820
TI  - Prevention and management of postoperative endophthalmitis: A case-based
      approach.
AB  - Endophthalmitis following intraocular surgery is a disastrous complication and
      can lead to poor visual outcomes and loss of globe integrity. It should be
      differentiated from toxic anterior segment syndrome (TASS) where management
      differs drastically. This article presents basic knowledge about postoperative
      endophthalmitis and describes nine different real-world scenarios ranging from
      TASS to milder forms of endophthalmitis responding to intravitreal antibiotics
      alone and more complicated forms associated with corneal involvement, fungal
      endophthalmitis and cases requiring intraocular lens removal, radical vitrectomy
      with hyaloid peeling, base dissection, and silicone oil. A case-based approach is
      followed where practical considerations have been adopted with each case such
      that it facilitates the readers' ability to apply theoretical knowledge to real
      life clinical situations.

PMID- 29208821
TI  - Redefining evidence in the management of acute post-cataract surgery
      endophthalmitis in India - The 2014 Adenwalla Oration, All India Ophthalmological
      Society.
AB  - The current evidence of postoperative endophthalmitis management in three
      important components of care-infection control, inflammation control, and
      prevention was reviewed, and their current relevance and application in an Indian
      context were evaluated. The publications from India indicated that Gram-negative
      bacterial and filamentous fungal infections are relatively higher. There are
      increasing instances of resistance to ceftazidime by Gram-negative
      microorganisms. Intravitreal dexamethasone limits inflammation in bacterial
      endophthalmitis when given together with the intravitreal antibiotics.
      Intracameral antibiotic could reduce postcataract surgery infection at least in
      less rigorous surgical environment. Systematic collection of data and periodic
      evaluation of the current practice against the new evidence are necessary to
      prevent or treat postcataract surgery endophthalmitis.

PMID- 29208822
TI  - B-HEX pupil expander: Pupil expansion redefined.
AB  - The B-HEX(r) Pupil Expander (Med Invent Devices) is a disposable 6.5 mm flexible
      hexagonal device with notches at corners and flanges at sides. Alternate flanges
      with positioning holes are tucked under the iris to engage the notches to the
      margin of the pupil to provide a 5.5 mm expanded pupil. Unlike devices with
      scrolls or pockets which require an injector to avoid snagging the incision, the
      preloaded B-HEX is inserted and removed through a 1 mm or larger incision using a
      manipulator or 23-gauge micro-forceps. The thin profile and uniplanar design
      allow unhindered instrument movement during phacoemulsification, cortical
      cleaning, and intraocular lens implantation. The B-HEX is safely used even after
      capsulorhexis since the thin uniplanar notches are directly visualized to avoid
      the capsule margin. It is useful in coaxial phacoemulsification, coaxial sub 2.00
      mm micro incision cataract surgery (MICS), biaxial 1.5 mm MICS, femtosecond laser
      assisted cataract surgery (FLACS), small pupil pars plana vitrectomy, and shallow
      anterior chamber eyes.

PMID- 29208823
TI  - Zepto precision pulse capsulotomy: A new automated and disposable capsulotomy
      technology.
AB  - Despite the appeal of an automated method of creating a perfectly circular
      anterior capsulotomy, global adoption of femtosecond laser capsulotomy (FSLC) has
      been limited by its high acquisition and per case cost. In addition, the
      femtosecond laser's large size and the need for eye docking create surgical
      efficiency and workflow challenges. The Zepto precision pulse capsulotomy (PPC)
      technology creates a circular anterior capsulotomy of a precise diameter using a
      disposable handpiece and tip that are used in the normal surgical sequence.
      Extensive preclinical and clinical testing has resulted in the US Food and Drug
      Administration (FDA) approval of the technology. Zepto PPC holds promise for
      complicated eyes such as those with intumescent or brunescent lenses,
      zonulopathy, or small pupils. This paper and the accompanying videos describe and
      demonstrate the technique and review the published studies.

PMID- 29208824
TI  - Terminal chop: New technique for full thickness nuclear segmentation in mature
      hard cataract.
AB  - We describe an efficient technique, "Terminal Chop," for full thickness nuclear
      segmentation in mature hard cataracts. Terminal chop utilizes the principle of
      secondary rock breakage system with stress concentration to break these hard
      nuclei. In this technique consonant to drag picks, a specially designed chopper
      "Terminator" is used to initiate a unique dispersive mechanical force to create a
      full thickness nuclear crack (crack formation) at the weakest soft and thin
      equator, which automatically traverses through the center and to the equator on
      the other side. Lateral separation of both the instruments placed at the equator,
      propagates the initial full thickness nuclear crack (crack propagation), breaking
      the entire nucleus into two complete pieces including the posterior plate. The
      direction of splitting follows the cleavage plane in a more direct manner, thus
      requiring least fracture force, least manipulation and stress, much lower than
      compressive stress, causing minimal trauma, and highly satisfactory postoperative
      results.

PMID- 29208825
TI  - Spatula scaffold: An iris-sparing technique for lensectomy.
AB  - Lensectomy with vitrectomy is often performed for crystalline lenticular
      subluxation. We report a new technique and a practical approach that involves the
      placement of a spatula beneath the iris tissue that facilitates retroiridial
      removal of subluxated lens and acts as a scaffold by protecting the iris tissue
      from being accidentally trapped into the vitrectomy cutter port. Our technique
      facilitates management of the lens and vitreous without any trauma to the iris
      and secondarily obviates the need to perform an iris repair procedure that may
      arise due to iatrogenic reasons.

PMID- 29208826
TI  - Limited vitrectomy in phacomorphic glaucoma.
AB  - One of the challenging situations for a cataract surgeon is phacoemulsification
      in the shallow anterior chamber like cases of phacomorphic glaucoma. Some of the
      main concerns of operating in a narrow space include endothelial decompensation,
      descemet's detachment, and posterior capsular rents. High vitreous pressure
      predisposes to posterior capsular rents owing to a reduced concavity of the
      posterior capsule and increasing the proximity of phaco-tip to the posterior
      capsule. We describe a technique of limited vitrectomy in such cases. A small
      gauge 23-G/25-G trocar cannula is passed transconjunctivally, and the liquefied
      vitreous is allowed to egress. Vitrectomy is done extraocularly till the vitreous
      pressure lowers down. This technique helps to debulk the vitreous and decompress
      the globe in a controlled manner. The resultant posterior displacement of iris
      lens diaphragm causes a deepening of the anterior chamber to facilitate
      phacoemulsification.

PMID- 29208827
TI  - Optimizing optical outcomes of intraocular lens implantation by achieving
      centration on visual axis.
AB  - In existing designs of intraocular lenses (IOLs), optical outcomes are
      compromised even after perfectly executed surgery. The reason for this is
      misalignment of optical axis of the eye and its visual axis. There is a need to
      design an IOL which compensates for this misalignment and hence enhances the
      optical outcomes of cataract surgery. The present innovation attempts to fulfill
      this unmet need and optimizes optical outcomes of all IOLs of different optical
      profiles - spherical, aspheric, toric, and multifocal. In addition, the
      improvised design of IOL offers other benefits such as delaying the formation of
      after-cataract and ameliorating negative dysphotopsia.

PMID- 29208828
TI  - A simple technique of intraocular lenses explantation for single-piece foldable
      lenses.
AB  - Foldable intraocular lenses (IOLs) are most commonly used in modern-day cataract
      surgery. Explantation of these IOLs is not frequently encountered, but sometimes
      extreme situations may demand the same. Commonly explantation is achieved by
      bisecting the IOL inside the anterior chamber with a cutter and delivering the
      pieces out one by one. This may require corneal wound extension with associated
      damage and endothelial loss leading to visual deterioration. We devised a simple,
      innovative IOL explantation technique utilizing a modified Alcon A cartridge and
      snare. This can successfully refold the IOL to be explanted inside the eye and
      deliver it out through the same wound. The device has limitations with very thick
      optic lenses, multipiece, and silicon IOLs. In conclusion, we describe a simple,
      innovative, and reproducible technique to explant almost any single piece IOL
      without compromising the original surgery and yielding very satisfactory
      outcomes.

PMID- 29208829
TI  - Comparative analysis of endothelial cell loss following phacoemulsification in
      pupils of different sizes.
AB  - PURPOSE: To compare Endothelial cell(EC) loss following Phacoemulsification (PKE)
      in pupils of different sizes. METHODS: A prospective double masked observational
      study in which a total of 150 eyes of 150 patients between 50 & 70 years of age
      with senile cataract of nuclear sclerosis grade II were enrolled. Patients were
      allocated into three groups of 50 eyes each in Group A (pupil size <5 mm), Group
      B (pupil size 5-7 mm) and Group C (pupil size >7 mm). Pupillary size was measured
      by determining the height of slit on slit-lamp biomicroscope examination. PKE was
      done by the same expert surgeon using vertical chop technique and a foldable
      intraocular lens was implanted in the capsular bag. Corneal EC count and
      pachymetry were performed twice and average of 2 readings was taken for the
      purpose of this study. Measurements were taken preoperatively and postoperatively
      on day 1, day 7 and day 30. RESULTS: The mean EC count loss on postoperative day
      1 in Group A was 19.45%, Group B 14.89%, Group C 10.19% with statistical
      significant difference between Group A and Group B, as also Group A and Group C.
      The difference was not significant between Group B and Group C, though there was
      a fall in EC count in Group C as well. Increase in corneal thickness on
      postoperative day 1 in group A was 5.43%, Group B 3.55%, Group C 2.14% with
      statistical significant difference between Group A and Group B, as also Group A
      and Group C with no difference in Group B and Group C. CONCLUSION: PKE done in
      eyes with maximal pupillary dilatation of <5 mm causes a greater EC loss and
      results in thicker corneas postoperatively as compared to eyes with pupillary
      dilatation of >5 mm at the end of one month.

PMID- 29208830
TI  - Lens decompression technique for prevention of intraoperative complications
      during phacoemulsification of intumescent cataract.
AB  - PURPOSE: To evaluate intraoperative complications during phacoemulsification of
      intumescent cataract using lens decompression technique. METHODS: Participants
      with intumescent cataract scheduled for phacoemulsification were recruited and
      divided into two groups. In both groups, after the anterior capsule was stained
      with trypan blue, the anterior chamber was filled peripherally with a dispersive
      ophthalmic viscosurgical device (OVD) followed centrally by a higher viscosity
      cohesive OVD (Healon GV). In Group 2, a 25-gauge needle was then inserted into
      the lens center and liquid cortex aspirated by pulling back on the syringe
      plunger. The outcomes measured were the incidence of capsular radial tears and
      the incidence of conversion to extracapsular cataract extraction (ECCE). RESULTS:
      In Group 1 (20 eyes), capsular radial tears occurred in four eyes, and in two
      eyes, the procedure had to be converted to ECCE. In Group 2 (20 eyes), no
      capsular radial tears or conversion to ECCE was reported. CONCLUSION: Lens
      decompression technique reduced the risk of capsular radial tears and conversion
      to ECCE during phacoemulsification of intumescent cataract.

PMID- 29208831
TI  - Long-term results of trypan blue dye irrigation in the capsular bag to prevent
      posterior capsule opacification: A randomized trial.
AB  - PURPOSE: To study the effect of capsular bag irrigation of trypan blue dye
      (0.06%) on posterior capsular opacification (PCO) in eyes undergoing
      phacoemulsification. METHODS: This was a randomized, trial conducted at a
      tertiary eye care center in central India. The study included 50 patients (100
      eyes) with senile cataracts who were scheduled for phacoemulsification and
      intraocular lens (IOL) implantation and were willing to undergo bilateral
      cataract surgery. One eye of each patient was randomized to one of two groups.
      The dye group received 0.2 ml of trypan blue injected in the capsular bag after
      cortical cleanup under air. The control group (other eye of the same patient)
      received 0.2 ml of balanced salt solution injected in a similar manner. PCO in
      the central 3 mm area of IOL optic was analyzed by a masked observer using an
      evaluation of PCO software computer analysis system at 6, 12, 24, and 36 months.
      RESULTS: The average age of patients was 62.05 +/- 6.22 in the dye group and
      64.92 +/- 7.16 years in the control group. The mean PCO score at 6 months was
      significantly lower in the dye group (0.10 +/- 0.15) than in the control group
      (0.22 +/- 0.30). There were no significant differences in the PCO scores between
      the two groups from 12 to 36 months. At the end of 3 years, eight eyes in the dye
      group and seven in the control group required YAG capsulotomy (P = 0.21).
      CONCLUSION: Capsular bag irrigation of trypan blue dye decreased the PCO score at
      6 months, but it had no effect at 36 months.

PMID- 29208832
TI  - Comparison of visual performance and after cataract formation between two
      monofocal aspheric intraocular lenses following phacoemulsification for senile
      cataract: A randomized controlled study.
AB  - PURPOSE: Monofocal aspheric intraocular lenses (IOLs) provide better visual
      outcome compared to other available IOLs following cataract surgery. However, the
      imported IOLs are expensive and are not affordable by all subset of patients in
      low- to middle-income countries like India. The aim of this study is to compare
      the safety and efficacy of a relatively low cost indigenous IOL (Acriol EC) with
      an imported aspheric IOL (AcrySof IQ). METHODS: A randomized controlled trial was
      conducted at a tertiary care centre. Two hundred and five eyes of 137 patients
      >45 years of age with uncomplicated age-related cataract were recruited. All
      cases underwent standard phacoemulsification and randomly assigned to one of the
      IOL implantations (Group I: AcrySof IOL; Group II: Acriol EC IOL). Primary
      outcome measure was best-corrected visual acuity (BCVA). Secondary outcomes
      included visual function (VF) score, spherical equivalent, contrast sensitivity,
      optical aberrations, and posterior capsular opacification. Independent t-test to
      compare two means; Mann-Whitney test; Pearson's Chi-square test, and McNemar's
      test were used for analyzing the nonparametric data such as incidence of
      posterior capsule opacification. RESULTS: There was no significant difference in
      the mean postoperative BCVA at 1, 3, 6, and 12 months in either group (P > 0.05).
      The contrast sensitivity, wavefront aberrations, VF score, and posterior capsular
      opacification were comparable between the groups except for higher-order
      aberrations and spherical aberration, which were higher in Group II. CONCLUSIONS:
      Acriol EC IOL provides visual outcomes comparable to other commonly used aspheric
      IOLs with comparable safety and efficacy at an affordable cost.

PMID- 29208833
TI  - Sutureless 27-gauge needle-assisted transconjunctival intrascleral intraocular
      lens fixation: Initial experience.
AB  - PURPOSE: The purpose of the study was to report our initial experience with the
      transconjunctival Intrascleral Intraocular Lens (SFIOL) fixation with modified
      Yamane's double-needle technique and flanged haptics. METHODS: This was a
      prospective interventional study that enrolled 31 consecutive patients undergoing
      SFIOL with the modified Yamane's technique. All patients underwent comprehensive
      evaluation including uncorrected and best-corrected vision, intraocular pressure,
      ultrasound biomicroscopy, endothelial cell density, and macular thickness using
      optical coherence tomography (OCT). We excluded patients with visually
      significant coexistent pathology such as corneal scars, macular pathology, and
      glaucoma. RESULTS: The mean age of subjects was 57 +/- 16.9 years and 23 were men
      (74%). Surgery was performed for aphakia following complicated cataract surgery
      in 10 eyes (32%), with lensectomy for subluxated/dislocated cataract in 6 eyes
      (19%), and with IOL explantation for subluxated/dislocated IOL in 15 eyes (48%).
      There were no intraoperative complications. Uncorrected visual acuity improved
      from median of 1.48 logarithm of minimum angle of resolution (logMAR) units
      (interquartile range [IQR] = 1.3-2 logMAR) at baseline to 0.3 logMAR (IQR = 0.2
      0.4 logMAR) at 6 weeks (P < 0.001) which was maintained at 6 months. There were
      no significant changes in endothelial cell density (P = 0.34) and OCT-based
      macular thickness (P = 0.31) at 6 months. Two eyes had slight IOL decentration.
      CONCLUSION: Our initial experience suggests that the Yamane's technique for SFIOL
      is a simple procedure with a short-learning curve and is independent of scleral
      flaps, tunnels, sutures, and fibrin glue. Using widely available 27-gauge needle
      instead of 30-gauge thin wall needle as originally described by Yamane makes it
      possible for the use of various three-piece IOLs available globally. Further
      studies are required for widespread acceptance of this technique.

PMID- 29208834
TI  - Sutureless glueless intrascleral fixation of posterior chamber intraocular lens:
      Boon for aphakic.
AB  - PURPOSE: To report results of intrascleral fixation of 3-piece IOL without the
      help of suture and glue. METHODS: Study included intrascleral fixation of haptic
      in 50 eyes by T-fixation technique. Preoperative and postoperative visual acuity,
      slit lamp and fundus examination, applanation tonometry, keratometry, biometry,
      optical coherence tomography, Scheimpflug imaging were done for extensive
      evaluation. Qualitative and quantitative data were summarized in the form of
      proportion and mean and standard deviation, respectively. The significance of
      difference was measured by Chi-square test or unpaired t-test or ANOVA whichever
      is appropriate. P < 0.05 was considered as statistically significant. RESULTS:
      There was one case in which haptic broke during handshake maneuver and another
      IOL was required. Postoperative complications included corneal edema (4%),
      increased intraocular pressure (6%), cystoid macular edema (2%), decentration
      (4%), and dislocation (2%), which were all managed to the level of good visual
      recovery. There was no significant change in corneal astigmatism. There was
      significant change found in best-corrected visual acuity and uncorrected visual
      acuity after surgery. CONCLUSION: This modified technique seems to be a good
      alternative in IOL implantation in eyes with deficient capsules in view of the
      decrease in the learning time and surgical time and risk for complications.

PMID- 29208835
TI  - Effects of Fuchs uveitis syndrome on the ultrastructure of the anterior lens
      epithelium: A transmission electron microscopic study.
AB  - PURPOSE: The purpose of the study was to investigate the electron microscopic
      findings of the lens epithelial cells (LECs) in patients with Fuchs uveitis
      syndrome (FUS) who suffered from cataracts and to compare those with age-matched
      controls. METHODS: This study was a prospective, comparative case series. The
      anterior lens capsules (ALC: basement membrane and associated LECs) were taken
      from 12 eyes of 12 cases of FUS and ten eyes of ten control patients. The ALCs
      were obtained from cataract surgery and prepared for transmission electron
      microscopy (TEM). RESULTS: There were no statistically significant differences
      regarding the age or gender between the FUS group and the control group (P >
      0.05). In the TEM examinations of the ALCs, all of the FUS cases revealed similar
      significant ultrastructural changes when compared to the control patients. In the
      FUS group, the LECs showed homogeneous thickening and irregularity which included
      some small vacuoles in different areas of the epithelial tissue. Moreover, in
      some areas of the LECs, widespread, oval-shaped, pigment clusters were detected.
      Conversely, in the control group, the LECs and all of their elements were in
      normal ultrastructural patterns, with the exception of some small intraepithelial
      vacuoles which were fewer and smaller than those in the FUS group. CONCLUSION:
      Ultrastructural analysis of the ALC of the patients with FUS disclosed some
      significant alterations which may be related to the summation of oxidative
      stress, intraocular inflammation, and iris atrophy.

PMID- 29208836
TI  - Clinical outcomes in traumatic pseudophacocele: A rare clinical entity.
AB  - PURPOSE: The purpose of this study is to evaluate the clinical outcomes in
      patients with traumatic pseudophacocele. METHODS: In this retrospective,
      interventional case series, scleral wound repair with pars plana vitrectomy and
      glued intrascleral fixation of an intraocular lens (glued IOL) was performed in 5
      eyes of 5 patients. Pupilloplasty was performed in 3 cases whereas aniridia glued
      IOL fixation was done in 1 case that had total avulsion and loss of iris tissue.
      The main outcome measures were best-corrected visual acuity (BCVA),
      intraoperative and postoperative complications during the entire follow-up
      period. RESULTS: The preoperative vision ranged from hand movement to perception
      of light in all the patients. The mean postoperative BCVA was 0.42 +/- 0.21
      Snellen's decimal equivalent (SDE) at final follow-up. Postoperatively, all the
      cases retained good visual acuity with case 1 and case 2 reporting 0.5 SDE, case
      3 had 0.33 SDE, case 5 had 0.67 SDE whereas case 4 had a final visual acuity
      limited to 0.1 SDE due to associated corneal opacity. The mean follow-up period
      was 20.2 +/- 11.7 months (range from 9 months to 36 months). The IOL was well
      centered, all the wounds were well apposed and the mean postoperative intraocular
      pressure was 14.6 +/- 1.95 mm Hg. No complications were reported in the entire
      follow-up period. CONCLUSION: The clinical outcomes of management of
      pseudophacocele were encouraging with retention of reasonably good visual
      potential in all cases.

PMID- 29208838
TI  - Endophthalmitis prophylaxis: My perspective.

PMID- 29208837
TI  - Antibiotic prophylaxis practice patterns for cataract surgery in India - Results
      from an online survey.
AB  - PURPOSE: The aim of this study is to assess the current antibiotic prophylaxis
      practice patterns for cataract surgery in India. METHODS: This was a
      questionnaire-based E-survey carried out at a tertiary eye care center in India.
      An E-mail invitation to complete an online 20 point questionnaire survey was sent
      to all members of the All India Ophthalmological Society with valid E-mail
      addresses using a digital E-mail service. Duplicate entries were prevented.
      RESULTS: Out of 1228 total respondents (8.2%) who completed the survey 38%
      reported using routine intracameral (IC) antibiotic prophylaxis. Another 7% place
      antibiotics in the irrigating solution. Of those using IC antibiotic prophylaxis,
      91% adopted this practice within the past 2 years; 92% are using moxifloxacin
      with 56% using a commercially available moxifloxacin formulation. Those
      predominantly performing phacoemulsification (43% vs. 25% performing mostly
      manual small incision cataract surgery, P < 0.001) and more than 500 cataract
      surgeries annually (45% vs. 33%, P < 0.001) reported greater use of IC
      moxifloxacin. Self-reported endophthalmitis rates were statistically
      significantly greater in those not using IC antibiotics (0.045% vs. 0.036, P =
      0.04). Although a majority of respondents believe that IC antibiotics are an
      important option (54%) and that it is important to have a commercially available
      solution (68%), many believe that other antibiotic prophylaxis methods are
      sufficient (31%). CONCLUSION: IC antibiotic prophylaxis for cataract surgery has
      sharply increased in India. In contrast to the West, intraocular moxifloxacin,
      which is commercially available in India, is preferred by the vast majority of
      users.

PMID- 29208839
TI  - Safety, efficacy and cost-effectiveness of consecutive bilateral cataract surgery
      on two successive days in tribes at base hospital through community outreach
      program: A prospective study of Aravali Mountain, North West India.
AB  - PURPOSE: The aim of the study was to evaluate the safety and efficacy of
      consecutive bilateral cataract surgery (CBCS) on two successive days in a single
      hospital visit. METHODS: Prospective study was conducted on 565 patients of
      various tribes of hilly area of West Rajasthan who had come to our hospital
      through community outreach programmed (CORP) between January 2015 and March 2016.
      Patients with significant bilateral cataract without any other ocular morbidity
      were advised bilateral manual small incision cataract surgery on two consecutive
      days. Intraoperative and postoperative complications were evaluated, and follow
      up was done at 1 week, 1 month, and 3 months. RESULTS: Out of 565 patients, 519
      underwent both eye surgeries. Second eye surgery was deferred for a later date in
      46 cases. Because of intraoperative and postoperative complications in the first
      eye, 31 had delayed surgeries while 15 patients refused to undergo another eye
      surgery either because of postoperative day 1 poor vision in the operated eye due
      to retinal pathologies (n = 8) or unwillingness (n = 7). The second eye surgery
      was performed for 519 patients, out of whom six had intra or postoperative
      complications. At 1 month follow-up, four patients had unilateral cystoid macular
      edema and three had prolonged postoperative inflammation. At 3 months, all
      patients were satisfied and had no complications. None of the patients had sight
      threatening complications such as endophthalmitis, corneal decompensation, or
      vitreoretinal complications. CONCLUSION: CBCS may be considered safe and cost
      effective for patients living in remote locations, dependent on CORP.

PMID- 29208841
TI  - Soemmering's ring.

PMID- 29208840
TI  - Awareness and eye health-seeking practices for cataract among urban slum
      population of Delhi: The North India eye disease awareness study.
AB  - PURPOSE: The objective of the study was to assess the awareness and health
      seeking practices related to cataract in urban slums of Delhi. METHODS: This
      study design was a population-based cross-sectional study. Participants aged 18
      60 years were recruited from randomly selected five slums of South Delhi. They
      were interviewed using a semi-structured interview schedule on awareness and eye
      health-seeking practices related to cataract. The practices were recorded if the
      respondents themselves or any other member of the family was diagnosed with
      cataract in previous 2 years. RESULTS: A total of 1552 respondents participated
      in the study, of which, 89.9% had heard of cataract but only (42%) were aware of
      any symptom of cataract. The common symptoms of cataract reported by the
      participants were white opacity in eyes (25.9%) and loss of vision (20.6%).
      Surgery as a treatment of cataract was known to only 559 (40.1%) participants.
      Awareness about surgery as treatment of cataract was significantly higher among
      people aged 45-60 years (adjusted odds ratio = 2.89, 95% confidence interval =
      2.11-3.97) and in educated people (adjusted OR = 3.69 95% CI = 2.37-5.73). Out of
      84 respondents who had been diagnosed with cataract, the health-seeking practices
      were observed by 70 (83.3%) participants. Among them, 51 (72.9%) had undergone
      surgery and another 19 (27.1%) had been advised to wait for surgery. Most of the
      operated patients 48 (94.1%) attended the postoperative follow-up. CONCLUSION:
      The study findings suggest the majority of participants have heard of cataract,
      but there is low awareness of its symptoms and treatment, and good eye health
      seeking practices observed for cataract in urban slum population. Gaps in
      awareness observed can be filled up by implementing proper eye health education
      programs.

PMID- 29208842
TI  - Implantation of a double iris-claw intraocular lens in an aphakic nanophthalmic
      eye.
AB  - A 55-year-old female with an aphakic nanophthalmic eye underwent a secondary
      intraocular lens implantation (IOL) with double Artisan aphakia iris claw IOLs
      (ICIOLs) and was evaluated in this research. The patient's preoperative best
      corrected visual acuity (BCVA) of the right eye was 0.4 (0.4 logMAR) (with +
      21.00 D), postoperative 1st and 3rd month, 1st year, and 3 years BCVAs were 0.4
      (0.4 logMAR). The intraocular pressure was 15 mmHg preoperatively, and 14, 12,
      12, and 15 mmHg postoperatively at 1st and 3rd month, 1st year, and 3 years,
      respectively. The preoperative endothelial cell density (ECD) was 2372 cells/mm2,
      and postoperative ECDs were 2352, 2391, 2246, and 2240 cells/mm2 at 1st and 3rd
      months, at 1st year, and 3 years respectively. In aphakic nanophthalmic eyes with
      inadequate capsular support, which require high IOL dioptry, the implantation of
      double ICIOLs (one in front of the iris and the other behind the iris) seems to
      be safe and provides good visual rehabilitation.

PMID- 29208843
TI  - Severe pigment dispersion after iris-claw phakic intraocular lens implantation.
AB  - A 23-year-old female patient presented 3 months after the implantation of an
      Artisan(r) phakic intraocular lens with a severe depigmentation of the iris and
      peripheral anterior synechiae. Explantation of the intraocular lens and
      goniosynechialysis were performed. Eleven months after the explantation
      appearance of the iris significantly improved. There was no loss of lines of
      corrected distance visual acuity. Severe pigment dispersion after the
      implantation of an Artisan(r) phakic intraocular lens may happen and may require
      explantation of the lens. Iris depigmentation may improve with time.

PMID- 29208844
TI  - A rare case of traumatic subretinal migration of crystalline lens, corroborated
      histologically.
AB  - Blunt trauma is the most common cause of posterior dislocation of the crystalline
      lens. We describe a rare case of subretinal migration of crystalline lens through
      the giant retinal tear following blunt ocular trauma. This incidental finding of
      subretinal dislocation of lens following blunt ocular trauma was confirmed on
      histopathological examination of the enucleated eye. This complication has not
      been described by histopathological examination in literature so far.

PMID- 29208845
TI  - Epilepsy among Systemic Lupus Erythematosus Patients: Insights from a Large
      Database Analysis.
AB  - OBJECTIVE: Epilepsy is characterized by a relevant epidemiological and clinical
      burden. In the extant literature, an increased risk of seizures has been
      described in several inflammatory/autoimmune disorders, including systemic lupus
      erythematosus (SLE). However, so far, relatively few and small size-based studies
      have been conducted. We aimed to investigate the link between seizure and SLE
      utilizing a large sample of subjects and extensive data analysis. METHODS:
      Patients with SLE were compared with age- and sex-matched controls regarding the
      prevalence of epilepsy in a cross-sectional study. Chi-square and t tests were
      used for univariate analysis and a logistic regression model was used for
      multivariate analysis. The study was performed utilizing the medical database of
      Clalit Health Services. RESULTS: The study included 5,018 patients with SLE and
      25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was
      found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using
      logistic regression, adjusting for multiple confounding factors, older age (>=70
      years) resulted as negative predictor (OR 0.42 [95% CI 0.27-0.62], p <0.001),
      whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI
      3.94-5.82], p < 0.001). Interaction between SLE and elderly age resulted in high
      OR of 5.47 for epilepsy (95% CI 2.53-11.9). CONCLUSION: Our study confirms the
      higher prevalence of epilepsy in SLE patients. Physicians should be aware of such
      findings and have a lower threshold for suspecting epileptic seizures in these
      patients. Further studies are needed to better elucidate the mechanisms by which
      SLE favors the insurgence of seizures.

PMID- 29208846
TI  - Evaluation of the Efficacy of Ultrasound-Guided Local Lauromacrogol Injection
      Combined with Aspiration for Cesarean Scar Pregnancy: A Novel Treatment.
AB  - OBJECTIVES: To evaluate the efficacy of ultrasound-guided local lauromacrogol
      injection combined with aspiration for treating cesarean scar pregnancy (CSP).
      METHODS: From July 2016 to December 2016, 18 patients diagnosed with CSP were
      treated with ultrasound-guided local lauromacrogol injection combined with
      aspiration. Clinical data and outcome were analysed. RESULTS: All patients were
      treated successfully. The amount of bleeding ranged between 10 and 50 mL. The
      duration of hospitalization ranged between 2 and 11 days. Serum beta-human
      chorionic gonadotropin (beta-hCG) decreased to the nondetectable level within 19
      41 days. Menstruation recovery occurred after 10-24 days of normalization of
      serum beta-hCG level. Reproductive functions were preserved, and there were no
      untoward effects or complications. CONCLUSIONS: Ultrasound-guided local
      lauromacrogol injection combined with aspiration is an effective CSP therapy, as
      it was associated with a high success rate, short hospitalization and fast
      recovery. However, its wider application and popularization have to be validated
      on a larger patient population affected by CSP.

PMID- 29208847
TI  - Effect of Etanercept on the Success of Assisted Reproductive Technology in
      Patients with Endometrioma.
AB  - AIMS: To determine the effects of a tumor necrosis factor inhibitor (etanercept)
      on pregnancy outcomes in patients with endometrioma who were treated with
      assisted reproductive technology. METHODS: Sixty-eight infertile patients who had
      endometrioma were included in our retrospective case-control study. We
      administered etanercept (Enbrel, 50 mg in 1 mL intramuscularly) to 19 patients on
      the second day of their previous menstrual cycle. All patients were treated with
      assisted reproductive technology. Pregnancy and live birth rates (LBR) were
      documented. RESULTS: When all other parameters (age, body mass index,
      infertility) are supposed to be constant, the clinical pregnancy rate was
      significantly higher in patients who used etanercept in an antagonist protocol
      than in patients who did not use etanercept (chi2 = 5.547; p = 0.019) but LBR did
      not reach a statistical significance (chi2 = 3.179; p = 0.075). The use of
      etanercept had an OR of 4.17 (95% CI 1.23-14.14) compared with not using
      etanercept for clinical pregnancy rate. The use of etanercept increased the rate
      of pregnancy (chi2 = 6.55; p = 0.01). The pregnancy rate with the use of
      etanercept had an OR of 4.23 (95% CI 1.35-13.25) compared with patients who did
      not use etanercept. In the same way, the use of etanercept increased LBR twofold,
      but it is not significant in the border line (chi2 = 3.771; p = 0.052).
      CONCLUSIONS: Etanercept may be a new non-hormonal therapy that may be an adjunct
      to treatment of infertile women with endometrioma. However, the safety of
      etanercept on embryos and fetuses has not been fully clarified.

PMID- 29208848
TI  - Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for
      Patients with Acute Lacunar Infarction.
AB  - BACKGROUND: Although increasing evidence has demonstrated that elevated
      homocysteine (Hcy) levels may be an important contributor for the development of
      cerebral infarction, rare studies focused on its diagnostic and early prognostic
      roles in acute lacunar infarction. METHODS: A total of 197 patients with acute
      lacunar infarction and 192 to form the control group were prospectively recruited
      between January 2013 and February 2017. Early neurological deterioration was
      defined as an increase of >=2 points in National Institutes of Health Stroke
      Scale or the decrease in Barthel index (BI) score at discharge. RESULTS:
      Univariate and multivariate logistic regression analyses revealed that higher
      levels of fibrinogen and Hcy were independently clinical predictors associated
      with lacunar infarction. Receiver operating characteristic curves analysis
      demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the
      area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff
      value of 15.5 MUmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were
      achieved for predicting lacunar infarction. Hcy was only significantly related
      with BI reduction in the males (30.5 [15.5-65.5] vs. 18 [15-24], p = 0.034) in
      the univariate analysis but not in the females and the multivariate analysis.
      CONCLUSIONS: Serum Hcy may be an independent diagnostic and not an early
      prognostic biomarker for patients with acute lacunar infarction.

PMID- 29208849
TI  - Possessions Including Poltergeist: "Are You There, Madness?"
AB  - Beliefs involving the devil and possession figured in the nosography of mental
      illness that alienists gradually established during the 19th century. The
      description of this form of cenesthetic hallucination resulted in "the possessed"
      being viewed as patients, which protected them from the trials and punishments
      they so frequently faced in earlier centuries. According to psychologists, this
      illusion of mental duality is linked to impairment of introspective capacities.
      Current brain imaging suggests inappropriate activity of the default mode
      network, which interferes with attentional systems during the hallucinatory
      episode.

PMID- 29208850
TI  - Carotid Artery Stenosis Contralateral to Acute Tandem Occlusion: An Independent
      Predictor of Poor Clinical Outcome after Mechanical Thrombectomy with Concomitant
      Carotid Artery Stenting.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemic strokes due to extra-/intracranial
      tandem occlusions (TO) of the anterior circulation are responsible for causing
      mechanical thrombectomy (MT). The impact of concomitant contralateral carotid
      stenosis (CCS) upon outcome remains unclear in this stroke subtype. METHODS:
      Retrospective analysis of prospectively collected data of 4 international stroke
      centers between 2011 and 2017. One hundred ninety-seven consecutive patients with
      anterior TO were treated with MT and acute carotid artery stenting (CAS).
      Clinical (including demographics and National Institutes of Health Stroke Scale
      [NIHSS]), imaging (including angiographic evaluation of CCS) and procedural data
      were evaluated. Favorable clinical outcome was defined as modified Rankin Scale
      (mRS) <=2 at 90 days. RESULTS: In 186 out of 197 TO patients preinterventional CT
      angiography was available for analysis, thereof 49 patients (26%) presented with
      CCS. Median admission NIHSS and procedural timings did not differ between groups.
      Reperfusion was successful in 38 out of 49 patients (78%) vs. 113 out of 148
      patients (76%) without CCS. In stark contrast, rate of favorable outcome at 90
      days differed significantly between groups (22 vs. 44%; p < 0.05). The presence
      of CCS in TO was associated with an unfavorable clinical outcome independent of
      age and NIHSS in multivariate logistic regression (p < 0.05). Final infarct
      volume was significantly larger in CCS patients (100 +/- 127 vs. 63 +/- 77 cm3; p
      < 0.05). Neither all-cause mortality rates (25 vs. 17%) nor frequency of peri
      interventional symptomatic intracranial hemorrhage differed between groups (7 vs.
      6%). CONCLUSION: For patients with anterior TO undergoing MT with concomitant CAS
      the presence of CCS >50% is an independent predictor of poor clinical outcome.
      This most likely cause is due to poorer collateral flow to the affected tissue.

PMID- 29208851
TI  - Alcohol Relapse After Liver Transplantation: Younger Women Are at Greatest Risk.

PMID- 29208852
TI  - Extremely High Serum Ferritin: An Instrumental Marker of Masquerading Adult-Onset
      Still's Disease with Hemophagocytic Syndrome.
AB  - BACKGROUND Adult-onset Still's disease (AOSD) is a rare multi-systemic
      inflammatory disorder of unknown etiology characterized by spiking fever,
      characteristic rash, and arthritis. It often associates with high serum ferritin
      levels. CASE REPORT An 88-year-old woman had fever of over 39 degrees C without
      response to extended-spectrum antibiotics for 6 days. She had non-specific
      erythema with infiltration on her trunk. She had leukocytosis with neutrophilia
      of 80%, mild hepatic dysfunction, normal level of rheumatoid factor and
      antinuclear antibody, thrombocytopenia, elevated d-dimer and soluble interleukin2
      receptor, extremely high serum ferritin (78 662 ng/mL), and splenomegaly.
      Although she had no arthritis or specific erythema, we made the diagnosis of AOSD
      according to Yamaguchi's criteria with disseminated intravascular coagulation
      (DIC) and hemophagocytic syndrome (HPS) after ruling out infections,
      malignancies, or other connective tissue diseases. Twelve percent of AOSD
      patients have HPS. The mean serum ferritin of AOSD with HPS was reported at 18
      179 ng/mL, which supported the diagnosis of AOSD because only a few other
      diseases could show such extremely high serum ferritin. Although she was treated
      with prednisolone (30 mg/day), her condition deteriorated and her left pleural
      effusion increased. Therefore, methylprednisolone 500 mg/day for 3 days was
      started followed by prednisolone 30 mg/day and immunosuppressive agent
      (Cyclosporine 50 mg/day), which improved her general condition, elevated C
      reactive protein levels, and extremely high serum ferritin levels. CONCLUSIONS We
      report the case of an elderly patient with severe AOSD, who developed HPS and
      DIC, whose extremely high serum ferritin level was useful in diagnosis.

PMID- 29208854
TI  - Study on Clinical Presentation and Outcome of Septic Abortion and Its
      Relationship with Person Inducing Abortion.
AB  - Abortion is a global problem. Maternal mortality and morbidity is still high due
      to uncontrolled abortion mainly induced abortion which may turn to septic
      abortion. A total of 50 cases of septic abortion cases admitted in Dhaka Medical
      College Hospital were included in this study. This cross sectional study was
      designed to find out the clinical presentation and outcome of septic abortion
      from January 2010 to January 2011. Out of 50 cases of septic abortion admitted
      where 44(88%) were induced abortion. Majority of the cases were parous (2-3
      parity 32%; 4-6 parity 38%; and 6+ parity 4%) and housewives 42(84%), living with
      their husbands 49(98%), hailing from urban, semi urban and urban slums. Nineteen
      (38%) having no education and 21(42%) had primary education. Most of the women
      20(45.45%) wanted no more child, decided to terminate pregnancy not to overburden
      their families or due to disturbed marital relationship. The termination of
      pregnancy was carried out in first trimester 20(40%) and between (13-16) weeks it
      was 17(34%). Complications of septic abortion still remain a lethal threat to the
      life and health of women. The death rate was found 6(12%). And the leading causes
      of death were generalized peritonitis with septicaemia 3(50%), septicaemia with
      renal failure 2(33.30%), septic abortion with Disseminated Intravascular
      Coagulation 1(16.70%). Effective and widespread contraceptive use and continuing
      health and sex education remain pivotal if the incidence of septic abortion and
      their complications are to be reduced.

PMID- 29208853
TI  - Investigations of Cartilage Matrix Degeneration in Patients with Early-Stage
      Femoral Head Necrosis.
AB  - BACKGROUND The purpose of this study was to explore changes in cartilage matrix
      in early-stage femoral head necrosis (FHN). MATERIAL AND METHODS Femoral head
      samples of patients with early FHN were collected during total hip arthroplasty
      (THA), high-field 7.0T MRI scans were performed in vitro, and the average T2
      values were calculated. Cartilage samples were obtained from the weight-bearing
      area (FHN group) and non-weight-bearing area (Control group), divided into 3
      equal parts and used for biochemical analysis, histopathological staining, and
      gene expression analysis. RESULTS T2 mapping of the femoral head specimens showed
      that the density distribution of cartilage surface was not uniform, and the
      average T2 value increased unevenly. Histological staining demonstrated that the
      number of chondrocytes was significantly decreased and they were irregularly
      arranged, SO staining was lost, and collagen fiber arrangement was slightly more
      irregular on the cartilage surface in the FHN group. The biochemical results in
      the FHN group showed that the water content increased significantly and the DNA
      content decreased significantly, while no significant changes in GAG and total
      collagen contents were detected. Gene expression analysis in the FHN group showed
      that SOX9 expression was significantly down-regulated, while COL10A1 and RUNX2
      expressions were significantly up-regulated. The expression of ACAN and COL2A1
      were decreased and COL1A1 was increased, but there was no significant difference
      compared with the Control group. CONCLUSIONS Taken together, the results of this
      study suggest that patients with early-stage FHN tend to have cartilage matrix
      degeneration, which provides new ideas for studying the pathogenesis of FHN and
      selecting treatment strategies.

PMID- 29208855
TI  - Detection of Ovarian Tumor by Color Doppler Ultrasonography and CA-125.
AB  - Ovarian cancer is the most frequent cause of death from all gynaecological
      malignancies because of its insidious onset, vague symptoms and late
      presentation. This cross-sectional study was carried out on purposively selected
      43 patients with suspected ovarian tumor in the Department of Radiology and
      Imaging in collaboration with the Department of Gynaecology and Obstetrics and
      Department of Pathology, Mymensingh Medical College Hospital, Bangladesh from
      January 2015 to December 2016 to assess the diagnostic performance of color
      Doppler ultrasonography and CA-125 in a combination described as Novel Index in
      detection of ovarian tumor. Highest number of patients of ovarian tumor
      10(23.26%) were in age group 35 to 44 years and 45 to 54 years with a mean of
      37.72+/-15.65 years with a range of 8-70 years. Histopathology findings revealed
      19(44.18%) benign tumors and 24(55.82%) malignant tumors. Sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV) and
      accuracy of Resistance Index (RI) in diagnosis of ovarian tumor were 91.67%,
      89.47%, 91.67%, 89.47% and 90.69% respectively. Sensitivity, specificity, PPV,
      NPV and accuracy of serum CA-125 were 83.33%, 89.47%, 90.90%, 80.95% and 86.04%
      respectively. Sensitivity, specificity, PPV, NPV and accuracy of Novel index were
      95.83%, 89.47%, 92.00%, 94.44% and 93.02% respectively. Novel index showed better
      diagnostic performance. Based on the current study it is concluded that the
      combination of color Doppler ultrasonography and serum CA-125 can be useful for
      diagnosis of ovarian tumor.

PMID- 29208856
TI  - Prevalence of GERD in Type II Diabetes Mellitus Patients Admitted in A Tertiary
      Care Hospital of Bangladesh.
AB  - Gastroesophageal reflux disease (GERD) is defined as symptoms or complications
      associated with regurgitation from the stomach and/or the duodenum to the
      esophagus. Patients with type II diabetes mellitus (DM) were known to have higher
      prevalence of GERD in the Western countries, but data on the impact of GERD on DM
      patients in our country are scarce. The aim of this cross-sectional study was to
      evaluate the presence of GERD in type II DM patients admitted at the Department
      of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from
      April 2015 to September 2015. A total of 137 type II DM cases were purposively
      collected. Reflux Disease Questionnaire (RDQ) was used to check the presence of
      GERD. Patient's characteristics, laboratory data, face-to-face interview data
      were analyzed. Out of 137 type 2 DM patients 108 were suffering from GERD giving
      a prevalence rate of 78.8% which is quite high. Pathophysiological factors like
      age, sex, duration of DM, weight, waist circumference (WC) had no significant
      difference between GERD-DM and non-GERD-type II DM patients. Only hypertension
      and frequent eating fatty food were found to have significant differences between
      the two groups. From the study findings it could be said that the higher rate of
      GERD in patients with type II DM may be associated with lifestyle factor and some
      pathophysiological factors like hypertension. Psychiatric factors may also play
      role in contributing GERD. Further in-depth and large scale studies are necessary
      in our country in this regard.

PMID- 29208857
TI  - Assessment of Subvalvular Apparatus in Patients with Rheumatic Mitral Stenosis:
      Comparison between 2D and 3D Echocardiography.
AB  - Mitral valve is the most involved valve in rheumatic heart disease especially in
      the form of mitral stenosis. Treatment options of mitral stenosis depend upon
      pattern, extent & the severity of disease and echocardiography has the key role
      in this area. Severity of involvement of subvalvular apparatus (SVA) is an
      important factor for determining the treatment option. 2D echocardiography (2DE)
      is conventionally used. With the advancement of echocardiographic technology 3D
      echocardiography (3DE) would offer better assessment of subvalvular apparatus.
      This study compared transthoracic 2D versus 3D echocardiography for assessment of
      SVA in chronic rheumatic mitral valve disease. This cross sectional observational
      study was done in University cardiac centre, Bangabandhu Sheikh Mujib Medical
      University, Dhaka, Bangladesh from May 2012 to October 2012. In this study,
      considering all ethical issues, data were collected from 50 subjects who
      underwent transthoracic 2D and 3D echocardiography for the assessment of extent
      and severity of mitral stenosis. Accurate measurement of Mitral valvular area is
      very important in assessment of severity, which is found similar by both 2DE
      (0.98+/-0.24cm2) and 3DE (0.92 +/-0.23cm2). But assessment of subvalvular
      involvement especially chordal adhesion can be done better by 3DE (p<0.001). This
      observation suggests superiority of 3DE for assessment of SVA in chronic
      rheumatic mitral stenosis. The result of the study demonstrates that 3DE is
      superior to 2DE for the assessment of SVA in chronic rheumatic mitral stenosis.

PMID- 29208858
TI  - Correlation of Troponin-I Level with Left Ventricular Ejection Fraction and In
      hospital outcomes after First Attack of Non-ST Segment Elevation Myocardial
      Infarction.
AB  - Coronary heart disease (CHD) is the most common cause of heart disease and is the
      single most important cause of premature death in developed world. Recognizing a
      patient with ACS is important because the diagnosis triggers both triage and
      management. cTnI is 100% tissue-specific for the myocardium and it has been shown
      to be a very sensitive and specific marker for acute myocardial infarction (AMI).
      Ventricular function is the best predictor of death after an acute coronary
      syndrome. It serves as a marker of myocardial damage, provides information on
      systolic function as well as diagnosis and prognosis. The study aimed at
      investigating the impact of elevated Troponin-I level on LV ejection fraction and
      in-hospital outcomes in patients with first attack of Non ST-segment Elevation
      Myocardial Infarction (NSTEMI). This prospective analytical study was conducted
      in the Department of Cardiology in Mymensingh Medical College Hospital from
      December 2015 to November 2016. Total 130 first attack of NSTEMI patients were
      included considering inclusion and exclusion criteria. The sample population was
      divided into two groups: Group I - Patients with first attack of NSTEMI with good
      LV function (LVEF: >=55%). Group II - Patients with first attack of NSTEMI with
      LV systolic dysfunction (LVEF: <55%). Then Troponin-I and LVEF levels were
      correlated using Pearson's correlation coefficient test. In this study mean
      Troponin-I of Group I and Group II were 5.53+/-7.43 and 16.46+/-15.79ng/ml
      respectively. It was statistically significant (p<0.05). Echocardiography showed
      that patients with high Troponin-I level had low ejection fraction (LVEF) and
      patients with low Troponin-I level had preserved ejection fraction (LVEF).
      Analysis showed that patients with severe left ventricular systolic dysfunction
      (LVEF <35%) had the highest level of Troponin-I with worse in-hospital outcomes
      and vice versa-the patients with the preserved systolic function (LVEF >=55%) had
      the lowest levels of Troponin-I with better in-hospital outcomes. In our study,
      it also showed that the levels of Troponin-I had negative correlation with LV
      ejection fraction levels, with medium strength of association (r= -0.5394,
      p=0.001). The study enabled us to conclude that, the higher was the Troponin-I
      level, the lower was the LV ejection fraction level and thus worse in-hospital
      outcomes in first attack of NSTEMI patients.

PMID- 29208859
TI  - An Evaluation of the Result of Fenestration and Discectomy for the Treatment of
      Prolapsed Lumber Intervertrebal Disc (PLID).
AB  - The aim of this study is to asses the result of fenestration and discectomy for
      the treatment of PLID. This Prospective quasi experimental study was conducted on
      29 Patient of PLID with different ages at Dhaka Medical College Hospital (DMCH),
      Dhaka, Bangladesh from July 2014 to June 2016. Post Operative outcome was
      assessed through Modified Macnab Criteria & Visual Analogue Score (VAS). The mean
      age of patient were 38.14+/-9.20 years and ranging from 24 to 55 years. The mean
      age of male was 37.21+/-9.72 years and female patient was 39.90+/-8.32 years.
      Overall subjective assessment of this study revealed that 79.2% patients had
      excellent functional outcome, 13.8% good and 6.9% fair and there was no poor
      functional outcome a according to modified Macnab criteria.

PMID- 29208860
TI  - High Wall Motion Score Index after Acute Myocardial Infarction is Associated with
      Worse In-Hospital Outcome.
AB  - Myocardial Infarction is a major cause of death and disability worldwide. The
      incidence of coronary heart disease is high and second most cause of death after
      cancer. This prospective study conducted on 100 patients admitted with first
      attack of acute myocardial infarction in the department of Cardiology in
      Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2012 to
      June 2013 who were observed 3 to 8 days of hospital stay without doing further
      echocardiography and evaluated the relationship between echocardiographic wall
      motion score index (WMSI) assessed within 24 hours of admission and in-hospital
      outcomes. Mean age was 53.24+/-10.17 years in WMSI <2 and 55.58+/-12.68 years in
      WMSI >=2 groups; difference was statistically non-significant (p>0.05). In both
      groups, males were predominant sufferer. Male-female ratio was 3.55:1 and the
      difference was statistically non-significant (p>0.05). As a risk factor, smoking
      was significantly higher in both groups but the difference was not statistically
      significant (p>0.05) between groups. Hypertension was 34(49.28%) cases in WMSI <2
      and 13(41.93%) cases in WMSI >=2 group; difference was not statistically
      significant (p>0.05). Diabetes mellitus was 13(18.84%) cases in WMSI <2 and
      16(51.61%) cases in WMSI >=2 group that was statistically significant (p<0.05).
      Dyslipidemia was 28(40.58%) cases in WMSI <2 group and 23(74.19%) cases in WMSI
      >=2 group that was statistically significant (p<0.05). Site of involvement of MI
      in WMSI <2 group were 39(56.52%) cases AMI (Anterior) and 30(43.48%) cases AMI
      (Inferior). In WMSI >=2 group, AMI (Anterior) were 29(93.55%) and AMI (Inferior)
      were 02(6.45%). It revealed that AMI (anterior) was significantly higher in WMSI
      >=2 group and AMI (Inferior) was significantly higher in WMSI <2 group. Heart
      failure class (Killip class) increases with the increasing of WMSI. In Killip
      class-I, 4(5.80%) were WMSI <2 and 01(3.23%) was WMSI >=2 (p>0.05). In Killip
      class-II, 8(11.59%) were WMSI <2 and 02(6.45%) were WMSI >=2 (p>0.05). In Killip
      class-III, 4(5.80%) were WMSI <2 and 13(41.94%) were WMSI >=2 (p<0.05). In Killip
      class-IV, 2(2.89%) were WMSI <2 and 05(16.13%) were WMSI >=2 (p<0.05) that was
      statistically significant. Arrhythmia was 14(20.29%) cases in WMSI <2 group and
      13(41.94%) cases in WMSI >=2 group that was statistically significant (p<0.05).
      Death was 2(2.90%) cases in WMSI <2 and 07(22.58%) cases in WMSI >=2 group that
      was statistically significant (p<0.05). Early mortality rate was greater in
      patients with both WMSI >=2 and a higher Killip's class. The higher the WMSI
      determined within 24 hours of admission, the worse the in-hospital outcome.
      Echocardiography is an affordable and readily available technique, which may be
      used to identify and stratify the risk following acute MI.

PMID- 29208861
TI  - Etiology of Early Renal Allograft Dysfunction and Comparison between Dysfunction
      and Function Group: A Single Center Study.
AB  - Over a period of two years thirty five renal allograft recipients & donors were
      evaluated to find out the aetiology of early renal allograft dysfunction, in the
      Department of Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka,
      Bangladesh from March 2010 to February 2012. A comparison was made between
      dysfunction & functioning graft group. Mean age of recipients were (36.4+/-9.4)
      years, mean age of donors were (41.7+/-8.3) years, with a male and female ratio
      of 3:1. Fifty percent recipients showed one heliotype match, ninety percent
      recipients were anti CMV antibody IgG positive, few were anti CMV antibody IgM
      positive. All kidney transplant recipients received same immunosuppressive drugs.
      Primary disease of the renal allograft recipients demonstrates that majority
      88.58% had glomerulonephritis, 5.72% had polycystic kidney disease, 2.85% had
      chronic pyelonephritis and another 2.85% had diabetic nephropathy. Among 35 renal
      allograft recipients 23(66%) showed early graft dysfunction, 12(34%) showed
      normal graft function. The etiology of early graft dysfunction showed, 50%
      developed acute rejection, 17% acute cyclosporine toxicity, 17% acute tubular
      necrosis, 8% had graft thrombosis and 8% developed recurrent glomerulonephritis.
      Sub-clinical rejection was detected in 20% cases. Comparison of donor
      characteristics between dysfunctioning and functioning graft groups revealed that
      age and sex were identically distributed between the groups (p=0.183 and p=0.087
      respectively). The mean serum creatinine of donor was significantly higher in the
      graft dysfunction group than that in the functioning graft group (113.5+/-12.6
      vs. 99.6+/-17.3; p=0.025), as well as the mean creatinine clearance rate was
      significantly less in the former group than that in the later group (82.1+/-13.5
      vs. 93.9+/-18.6, p=0.040). The mean cyclosporine (C2) level on 7th POD were
      1593.2+/-320.4ng/ml in graft dysfunction group and 1439.1+/-199.5ng/ml in the
      functioning graft group which decreased to 1364.8+/-263.7ng/ml and 1114.2+/
      145.1ng/ml after three months in the dysfunction and the functioning graft groups
      respectively. There was no significant difference in the cyclosporine level
      between groups on 7th POD and 14th POD, 1st and 2nd month. However, at 3rd month
      the level of cyclosporine was higher in the dysfunction group than that in the
      function group. Proteinuria on 14th POD was almost similar between dysfunction
      and function graft groups (p=0.704). However, higher incidence of proteinuria was
      observed in subsequent months in the graft dysfunction group compared to the
      function graft group. All the postoperative variables like systolic blood
      pressure, diastolic blood pressure, fever and tremor were higher in dysfunction
      group in comparison to functioning graft group. Per operative biopsy of donor
      kidney, some showed increased number of sclerotic glomeruli which is more common
      in dysfunction group. Among 35 recipients 2(16.7%) died due to infection in
      dysfunction group compared to 1(4.3%) in functioning graft group.

PMID- 29208862
TI  - Impact of Magnetic Resonance Imaging in the Diagnosis of Pituitary Adenoma.
AB  - Pituitary adenoma is the third most common primary intracranial neoplasm
      involving the adult population with clinical features due to excess or deficient
      hormone secretion or due to its mass effect. Debate about the diagnostic
      accuracy, sensitivity and specificity of MRI imaging in detecting pituitary
      adenoma has been continuing. The study was aimed to evaluate the accuracy,
      sensitivity and specificity of MR imaging in detecting pituitary adenoma. This
      cross sectional study was conducted in the Department of Radiology and imaging,
      Bangabandhu Sheikh Mujib medical University (BSMMU) from July 2013 to August
      2015. It was carried out in 50 pituitary adenoma cases of which, 28 male and 22
      female to see the impact of MRI in the diagnosis of pituitary of adenoma. Out of
      50 cases 43 cases were diagnosed by MRI, 3 were normal and 2 were pituitary
      apoplexy, one was immature teratoma as confirmed through histopathology. So, MRI
      has got major impact in the diagnosis of pituitary adenoma.

PMID- 29208863
TI  - Short-segment versus Long-segment Stabilization for Unstable Thoracolumbar
      Junction Burst Fractures.
AB  - The treatment of unstable thoracolumbar junction burst fractures remains a
      controversial issue. We evaluate the efficacy of short segment (SS) compared with
      that of long-segment (LS) stabilization in terms of clinical and the radiological
      outcomes. Records of 88 patients with thoracolumbar burst fracture underwent
      posterior pedicle screw fixation from January 2004 to December 2015, studied
      retrospectively. These patients were divided into two groups: SS and the LS
      group. Clinical parameters: back pain, disability, neurological deficit and
      radiologic parameters: Cobb angle, sagittal index, the kyphotic deformation of
      vertebral body, vertebral height and canal compromise were measured before
      surgery and immediately after surgery and at 3, 6 and 12 months postoperatively.
      Overall outcomes were evaluated using the modified Mcnab criteria at the last
      follow-up. Chi-squared test and paired-t test were used for statistical analysis
      using SPSS. There were 36 and 52 patients in the SS and LS- group, respectively.
      The mean age of the patients was 30.6+/-8.4 and 33.4+/-8.4 years and the mean
      follow-up period was 24.5 and 16.8 months in SS and LS-group respectively. In the
      SS-group, the fractured vertebral body level was L1, T12, L2, T11 and T10 in 15,
      10, 6, 3 and 2 cases and LS- group, the fractured vertebral body level was L1,
      T12, L2, T11 and T10 in 22, 17, 5, 5 and 3 cases, respectively. Both groups
      achieved satisfactory clinical outcomes according to the modified Mcnab criteria.
      In the SS-group, 8(22.22%), 21(58.33%) and 7(19.44%) cases were considered to
      have excellent, good and fair outcome and LS-group, 18(34.61%), 25(48.08%),
      6(11.54%) and 3(5.77%) cases were considered to have excellent, good, fair, and
      poor outcome, respectively. Short-segment pedicle screw fixation including the
      fractured vertebral body might be as effective as long-segment pedicle screw
      fixation for the treatment of unstable thoracolumbar junction burst fracture.

PMID- 29208864
TI  - How Does Family Structure Relate With Children's Language Development? A Cross
      Sectional Experience from Urban Slums in Dhaka.
AB  - Family structure is an important factor for children's overall development. In
      this cross sectional study, we explored how single parenting relates to child's
      language development in slums of Dhaka city, Bangladesh from 31st August 2010 to
      9th February 2011. Children aged 10 to 24 months (n=133), living with mother only
      and those living with both parents were included. Children's comprehensive and
      expressive language development was assessed using the Bengali version of Mac
      Arthur's Communicative Development Inventory (MCDI). Family care indicators (FCI)
      were used to assess quality of psychosocial stimulation at home, maternal
      depression was assessed using Centre for Epidemiological Studies - Depression
      (CES-D) questionnaire and socioeconomic status (SES) of the family was determined
      using a previously tested questionnaire. We analyzed the data using multivariate
      analysis. Maternal depression scores were higher in single mothers compared to
      those living with their husband and more depressed mothers provided less
      stimulating environment for the child. Children in the single parent families had
      lower scores on FCI and their comprehension and expression scores were slightly
      lower. Multiple regressions analysis showed that children's comprehension {B
      (95%CI), 0.19 (0.07, 0.32), p=0.003} and expression {0.18 (0.02, 0.35), p=0.032}
      scores were significantly higher in those living with both parents. Steps to
      educate parents on the importance of a healthy family life needs to be taken in
      order to ensure development of children to achieve their full potentials. Further
      long-term effects of living without father on children's development needs to be
      explored in Bangladesh.

PMID- 29208865
TI  - Assessment of Postnatal Depression by Edinburgh Postnatal Depression Scale in a
      Tertiary Care Hospital of Bangladesh.
AB  - The objective of the study was to estimate the prevalence of post partum
      depression and its associated risk factors among the mothers in their immediate
      post natal period. This cross sectional study was carried out in the Department
      of Obstetrics & Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU)
      and a tertiary care centre in Dhaka, Bangladesh from July 2015 to December 2015.
      Total 145 post natal mothers were screened for postnatal depression from day 5-7
      following caesarean section by the validated Bangla version of Edinburgh
      Postnatal Depression Scale. To find out the risk factors for depression baseline
      data included age, parity, socioeconomic conditions, educational level, and
      occupation, history of depression, social support, and marital support,
      gestational age at the time of delivery, weight and sex of the baby. Postpartum
      depression was noted among 12.4% cases. Maternal age, history of depression, lack
      of social support was found to be significantly associated with maternal
      depression. This small study reflected the facts that many of the postnatal
      mothers of our circumstances suffer from postpartum depression and needs medical
      attention. Screening of postpartum depression can be considered as a routine part
      of postpartum care.

PMID- 29208866
TI  - Acute Kidney Injury in Patients with Acute Viral Hepatitis: A Study in a Tertiary
      Care Hospital.
AB  - This cross sectional observational study was done in the Department of Medicine,
      Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from May 2013
      to April 2014 to find out the proportion of acute kidney injury among patients
      with acute viral hepatitis and to identify risk factors associated with
      development of acute kidney injury (AKI). A total of 100 patients with acute
      viral hepatitis were included purposively as study subjects. Among them 61 were
      male and 39 were female. They were divided into AKI group (n=6) and non-AKI group
      (n=94) on the basis of development of AKI. There was no significant difference in
      mean age (39.0+/-13.1 years vs. 32.2+/-10.8 years, p=0.335) and sex (67% vs. 61%
      & 33.0% vs. 39.0%) p=0.769) between AKI group and non-AKI group. There were 27%
      acute viral hepatitis A, 21% acute viral hepatitis B and 52% acute viral
      hepatitis E but no case of acute viral hepatitis C was found in this study. Acute
      kidney injury (AKI) developed in 6 of 27 patients with acute viral hepatitis A.
      This study showed that 22.2% patients with acute viral hepatitis A developed
      acute kidney injury but patients with acute viral hepatitis B (HBV) and hepatitis
      E (HEV) did not develop acute kidney injury. Majority of the patients with acute
      kidney injury were smokers and hypertensive with elevated mean arterial pressure
      (p=0.0001) at presentation and had higher total bilirubin (p=0.0001), alanine
      aminotranseferase values (p=0.040), prolonged prothrombin time (INR) {p=0.0001},
      lower albumin (p=0.0001), lower haematocrit level (p=0.0001), high CRP
      concentration (p=0.0001), leucocytosis (p=0.0001) and thrombocytopenia (p=0.0001)
      at presentation than patients without acute kidney injury. It is evident from the
      study that acute kidney injury is not a rare complication in patients with acute
      viral hepatitis.

PMID- 29208867
TI  - Surgical Treatment of Hepatolithiasis: Our Experience in Bangabandhu Sheikh Mujib
      Medical University.
AB  - Recurrent cholangitis and sepsis are common complications after surgical
      treatment for hepatolithiasis as total clearance is not always possible. This
      retrospective study is designed to see the effect of our treatment for
      hepatolithiasis on stone clearance and post operative complications. We have
      treated 60 patients with hepatolithiasis surgically from September 2010 to
      September 2016 in the Department of Surgery, Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka, Bangladesh. Various operative procedures were applied
      on the basis of location of stone and status of biliary tree. Choledocoscopic
      examination was performed during surgery for checking and cleaning of
      intrahepatic duct. Regular follow up was given and outcome was assessed. The
      chronological changes of treatment methods for patients with hepatolithiasis were
      analyzed for appropriate treatments for particular type. There were 22 males and
      38 females with age ranges from 15 to 60 years. The stone were located in left
      duct (56.6%), right duct (10%) and both duct (33.4%). The most commonly performed
      operation was extended choledocholithotomy and hepatolithotomy and it was
      performed in 28 patients (46.7%). Segmentectomy and lobectomy was performed in 17
      patients (28.3%). Common bile duct (CBD) excision, hepatolithotomy and
      hepaticojejunostomy with or without segmentectomy, lobectomy and Houston access
      loop formation was performed in rest of the patients. Stones could be removed
      completely in all patients who underwent lobectomy or segmentectomy. In contrast
      stone clearance was possible only in 57.2% and 55.5% who underwent extended
      choledocholithotomy and hepatolithotomy, and excision of CBD, hepatolithiasis
      with hepaticojejunostomy for unilateral or bilateral hepatolithiasis
      respectively. Houston's access loop to stomach was made in 2 patients for future
      endoscopic removal of stone. There was no mortality in the present series but
      morbidity occurred in 18 patients; wound infection (n=15, 25%), bile leakage
      (n=1, 1.7%), and renal dysfunction (n=1, 1.7%), septicemia (n=1, 1.7%). Patients
      who underwent lobectomy or segmentectomy did not develop cholangitis or sepsis on
      1 to 3 years follow up. In contrast who underwent extended choledocholithotomy
      and hepatolithotomy, 70.8% patients developed cholangitis and sepsis, and the
      patients who underwent excision of CBD, hepatolithotomy with hepaticojejunostomy
      50% developed cholangitis and sepsis within 1 to 3 years of follow up, required
      re-operations or conservative treatment. The difference of developing
      postoperative cholangitis and sepsis is significant (p<0.05) between patient who
      underwent extended choledocolithotomy and hepatolithotomy, and who underwent
      excision of CBD, hepatolithotomy and Roux-en-Y hepaticojejunostomy. In
      conclusion, lobectomy or segmentectomy is the best option for hepatolithiasis if
      the stones are limited to a lobe or segment. Excision of CBD, hepatolithotomy
      with hepaticojejunostomy is better than extended choledocholithotomy and
      hepatolithotomy for bilateral hepatolithiasis. Huston's access loop formation
      associated with other procedures may be considered for bilateral hepatolithiasis
      for future minimal invasive stone retrieval procedure as residual stones and
      recurrent stone formation is common.

PMID- 29208868
TI  - Detection of Plasmid Mediated AmpC-beta lactamases Among Gram-Negative
      Uropathogens at a Tertiary Care Hospital, Dhaka City.
AB  - Plasmid-mediated AmpC beta-lactamase (PMABL) resistance among gram negative
      bacilli is an emerging problem worldwide. They likely originate from chromosomal
      AmpC of certain Gram-negative bacterial species and subsequently are mobilized to
      transmissible plasmids. There are reports of unfavorable clinical outcomes in
      patients infected with these organisms and treated with broad
      spectrumcephalosporins. The present cross sectional study was designed to detect
      PMABL genes among gram negative uropathogens in a tertiary care hospital, Dhaka
      city, Bangladesh from January 2014 to December 2014. Total 138 gram negative
      uropathogens were identified by the conventional methods and were screened for
      AmpC production using cefoxitin discs. Confirmatory phenotypic identification was
      done by modified three dimensional test (MTDT). The common AmpC genotypes ACC,
      FOX, MOX, DHA, CIT and EBC types were determined by a multiplex PCR.PMABL genes
      were detected by PCR in 90% of cefoxitin resistant isolates and the molecular
      types of the genes detected predominantly were CIT, DHA followed by EBC and ACC
      types. Overall, PMABL genes were detected in 32.61% (45/138) of the studied gram
      negative uropathogens which is alarming. All (100%) the plasmid mediated AmpC
      beta-lactamase producers showed resistance to amoxicillin-clavulanic acid,
      ceftazidime, ceftriaxone, cefotaxime and cefoxitin. These results emphasize that
      clinical laboratories should consider the tests for the detection of PMABL genes
      for infection control and formulation of effective antibiotic policy.

PMID- 29208869
TI  - Prediction of Un-erupted Canine and Premolar Tooth Size in Mixed Dentition among
      Bangladeshi Population.
AB  - Accurate prediction of the space available to accommodate the size of the un
      erupted canines and premolars plays an important role in mixed dentition in
      Orthodontics. This Descriptive cross sectional study was carried out in the
      Department of Orthodontics of Bangabandhu Sheikh Mujib Medical University from
      July 2014 to June 2015. Dental study models of 140 patients were taken as sample.
      The sample was consisted of 54 Bangladeshi males and 86 females aged between 12
      to 17 years and without any previous orthodontic treatment fully erupted
      permanent teeth and with no dental anomalies were recruited. The study was done
      by measuring the mesio-distal dimensions of teeth over the dental cast. A pre
      structured data collection form which includes the particulars of the patient and
      data was filled. All patients were having a serial number to maintain their
      confidentiality. The study protocol was approved by "Institutional Review Board"
      of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Un
      paired t test were used to examine differences between genders, correlation
      coefficients and linear regression equations were used to carry out the analysis.
      Descriptive statistics including means, standard deviations, and minimum-maximum
      values were calculated. Unpaired sample 't' tests were carried out to compare
      tooth size between the sexes. Logistic regression for development of new
      prediction formula on the basis of study sample of our population. Pearson
      correlation coefficient test for found the correlation between mandibular
      incisors and mandibular and maxillary canine and premolars in each quadrant. The
      difference between the present study with that of Moyers and Tanaka and Johnston
      were statistically significant (p<0.001). The values from Moyers and Tanaka and
      Johnston methods exceed while comparing to Bangladeshi population. Therefore,
      Moyers and Tanaka and Johnston method of prediction are not applicable for our
      population.

PMID- 29208870
TI  - A Comparative Study of Magnetic Resonance Imaging and Transabdominal
      Ultrasonography for the Diagnosis and Evaluation of Uterine Fibroids.
AB  - Uterine fibroids often cause symptoms of pelvic pain, pressure, and bleeding and
      a significant cause of morbidity for women of reproductive age. A new, Food and
      Drug Administration approved noninvasive treatment option is magnetic resonance
      guided focused ultrasound surgery, which has the potential to become a treatment
      of choice for selected patients. The purpose of the study was to compare and
      evaluate the usefulness of MRI and transabdominal ultrasonography for the
      diagnosis of uterine fibroids. A cross sectional study was carried out in the
      department of Radiology & Imaging of Mymensingh Medical College Hospital, during
      the period of January' 2010 to December 2011. A total number of 40 consecutive
      patients having suspected uterine fibroids underwent MRI and transabdominal
      ultrasonography and they were followed up from the admission upto the tissue
      diagnosis of uterine fibroids for histopathological correlation were included in
      this study. The test of validity of MRI and transabdominal ultrasonography in
      diagnosis of uterine fibroids was calculated. In the diagnosis of uterine
      fibroids, USG was 88.2% sensitive, 66.7% specific, 85.0% accurate, 93.8% positive
      predictive values and 50% negative predictive values. However MRI was 97.1%
      sensitive, 83.3% specific, 95.0% accurate, 97.1% positive predictive values and
      83.3% negative predictive values for prediction of uterine fibroids. The study
      shows that the MRI is more efficient diagnostic modality than transabdominal
      ultrasonography in detecting uterine fibroid presence and evaluation.

PMID- 29208871
TI  - Management of Infected Sebaceous Cyst by Suture Closure: A New Approach.
AB  - Incision and drainage is the management plan of any infected sebaceous cyst from
      old age. But in infected sebaceous cyst, we can treat it in a simple way.Under
      local or general anesthesia the infected tissue is excised along with a rim of
      healthy tissue and then closed by Prolene in the same sitting. Usually stitches
      are removed on 21st day in the back and 14th day in the limb. This cross
      sectional observational study was carried out in the Department of Surgery of 250
      Bed District Hospital, Kishoreganj and local clinics of Kishoreganj, Bangladesh
      from January 2012 to March 2015. One hundred (100) cases were selected with
      clinical diagnosis of infected sebaceous cyst and the procedure was carefully
      explained to every patients. The overall results were analyzed and it was
      revealed that with this method patients got quick recovery and no need for
      frequent dressing which prevents cross infection. It is cost effective and saves
      time also.

PMID- 29208872
TI  - Age and Gender-dependent Correlates as Risk Factors of Recurrent Headache among
      Bangladeshi Secondary School Children.
AB  - Magnitude of recurrent headache (RHA) is not well explored among school-children
      (schoolers) particularly in developing countries like Bangladesh, though recent
      literature reveals that RHA connotes serious public health implication(s)
      particularly in schoolers in resource constraint countries. To study age and
      gender-dependent correlates of RHA among secondary-level schoolers and to
      determine if these remains its risk-factors. Cross-sectional population based
      respondent-dependent study employing direct interviews using pre-tested open and
      closed-ended questionnaire following ICHD-II (2004) diagnostic criteria. Overall,
      17% RHA was observed among 1499 schoolers surveyed initially, being more in
      pubertal/adolescents (13-15 years) than pre-pubertal (11-12 years) ones. Of
      screened-out 255 RHA positive cases, migraine (MHA) was observed in 55.3% while
      tension-type-headache (TTH) in 19.6% schoolers. RHA demonstrated a steady
      inclining trend with schooler's age. Gender difference was obvious in MHA
      (p<0.001) but not in TTH (p<0.31). Pubertal schoolers (OR=8.75) and boys (OR=1.8)
      remained at greater risk for migraine but less risky for TTH. Mass-awareness
      program is imperative to prevent RHA among schoolers towards progressing it into
      chronicity, psycho-socially handicapped and economically burdened. Further in
      depth studies warrant prudent data to examine its long-term risks/underlying
      factors involving more diverse population (school-children) from different
      geographical areas and cultural contexts.

PMID- 29208873
TI  - Correlation between Seropositivity of Chlamydia Trachomatis and Tubal and/or
      Pelvic Pathology Detected by Diagnostic Laparoscopy in Subfertile Women.
AB  - This prospective observational study was carried out in the Infertility Unit,
      Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka, from February 2011 to December 2013. Sixty-nine (69)
      subfertile women who were seropositive for Chlamydia Trachomatis were included in
      this study. Inclusion criteria was patients with sub-fertility having age between
      22 and 40 years, seeking infertility treatment, normal ovarian function, all
      normozoospermic male partner, duration of infertility ranged from 1.5 to 14
      years. Exclusion criteria were patients having sub-fertility with extensive
      pelvic and/or ovarian surgery, endometriosis, ablation of endometriotic spots,
      pelvic tuberculosis and history of ectopic pregnancy. Before laparoscopic
      evaluation, all study women were screened for Chlamydia Trachomatis Specific IgG
      & IgM antibodies using ELISA in the Microbiology Department of Bangabandhu Sheikh
      Mujib Medical University (BSMMU), Dhaka, Bangladesh. All the study women had
      positive results for IgG antibodies. All study women underwent diagnostic
      laparoscopy. During laparoscopy, we observed the condition of pelvic cavity,
      uterus, fallopian tubes, ovaries, peritubal adhesions, tubo-ovarian relationship,
      status of Pouch of Douglas (POD), fimbriae etc. During dye test procedure, dilute
      methylene blue dye was injected through the cervical canal and the dye spill out
      was observed to confirm the tubal patency or blockage or pattern of flow of dye.
      The results of laparoscopic findings demonstrated that mobility of uterus was
      restricted in 20(29%) cases, adhesion of uterus with peritoneum was in 8(11.6%)
      cases, uterine fibroid was present in 11(15.9%) cases, hydrosalpinx in right
      fallopian tubes were in 27(39.1%) cases, in left fallopian tubes were in
      32(46.4%) cases and in both fallopian tubes in 16(23.2%) cases, inflamed right
      fallopian tubes in 32(46.4%) cases, inflamed left fallopian tubes in 36(52.2%)
      cases and inflamed both fallopian tubes in 26(37.7%) cases, adhesions in pouch of
      Douglas was in 4(5.8%) cases, collections in pouch of Douglas was in 7(10.1%)
      cases and obliterations in pouch of Douglas was in 5(7.2%) cases. Results of Dye
      test during laparoscopy were that right fallopian tube was blocked in 32(46.4%)
      cases, left fallopian tube was blocked in 32(46.4%) cases and both fallopian
      tubes were blocked in 21(30.4%) cases. This study shows that by laparoscopy,
      significant number of cases of tubal and pelvic pathology was diagnosed in the
      chlamydia trachomatis seropositive subfertile female. This indicates strong
      correlation between seropositivity of chlamydia trachomatis and/or pelvic
      pathology detected by diagnostic laparoscopy.

PMID- 29208874
TI  - Status of Baby Friendly Hospital Initiative in Neonatal Units.
AB  - Neonatal unit is more vulnerable and critical ward than any others. To assure
      breastfeeding in neonatal unit is one of the ways to reduce child morbidity and
      mortality. Baby friendly hospital initiative is the best method in hospital
      setting to assure breastfeeding. This cross-sectional descriptive study was
      conducted from July 2014 to December 2014 to find out the Status of Baby Friendly
      Hospital Initiative (BFHI) in neonatal unit of different public hospitals. The
      study area was consisting of several tertiary level hospitals in Dhaka city.
      Study was done in those hospital where declared as Baby Friendly Hospital
      Initiative. Total 137 data was collected from care givers (70) and healthcare
      providers (67). From hospital data it was found that all children discharged for
      last month were exclusively breastfed. Written breastfeeding policy was present
      in all hospitals but out of 67 staffs only 28(41.48%) staffs received training
      which was not fulfillment of the requirement of Global Criteria of UNICEF/WHO
      (BFHI External Assessment and Reassessment). In step 5 only 21(31.34%) staffs
      show or offered help for breastfeeding. In step 6 and 9 there were 100% fulfill
      the requirements, no teats and pacifier was found, no use of foods or drinks
      except medications. Nurses were co-operative but due to lack of training and
      motivation they were not fully aware about the importance of breastfeeding.

PMID- 29208875
TI  - Predicting Neonatal Hyperbilirubinemia Using First Day Serum Bilirubin Level in
      Late Preterm and Term Healthy Newborn.
AB  - Hyperbilirubinemia is a common problem during the neonatal period and is the most
      common reason for readmission after early hospital discharge of the healthy near
      term and term infants. This early discharge policy along with limited follow-up
      facilities in developing countries and inadequate communication between
      physicians and parents necessitates a prognostic test to predict
      hyperbilirubinemia in these newborns; for early and effective management and
      prevention of potential complication before it occurred. This observational
      analytical study was done to determine the predictability of day1 total serum
      bilirubin (TSB) level as a screening test and identify the best cutoff value
      which would predict neonates likely to develop significant hyperbilirubinemia.
      The study was carried out in the Department of Neonatology and Department of
      Gynecology and Obstetrics, Bangabandhu Sheikh Mujib Medical University (BSMMU),
      Dhaka, Bangladesh from 1st April 2013 to 31st March 2014. A TSB level of
      >=17mg/dl after 72 hours was defined as significant hyperbilirubinemia. By
      purposive sampling method, 100 healthy late preterm and term neonates fulfilling
      the inclusion criteria were enrolled and 89 were finally analyzed. Among 89
      neonates 14(15.74%) developed significant hyperbilirubinemia (Group II) and
      75(84.26%) did not develop hyperbilirubinemia (Group I). Mean time of sample
      collection was similar in both groups. Mean TSB level on day1 was significantly
      higher in Group II (5.97+/-1.74mg/dl) than Group I (3.19+/-1.4mg/dl). By using
      ROC (Receiver Operating Characteristic) analysis, TSB level of 5.65mg/dl on day 1
      has the best combination of sensitivity (86%) and specificity (91%) to predict
      neonates at risk of significant hyperbilirubinemia (AUC-0.880, p=0.001). At this
      cut-off PPV was 63% and NPV 97%. Total serum bilirubin level on first day of life
      predicts neonates at risk of subsequent significant hyperbilirubinemia and late
      preterm and term babies with TSB level of >=5.65mg/dl on day 1 of life should be
      followed up strictly either in the hospital or in the outpatient department on
      day 5.

PMID- 29208876
TI  - Disease Pattern among Children attending Pediatric Outpatient Department in
      Community Based Medical College Hospital, Bangladesh.
AB  - Disease pattern is based on socio-demographic characteristics, comprehensive
      health care services, and environmental variables like water supply, basic
      sanitation and housing, illness behavior like quick decision to arrive at health
      care facility, and treatment behavior like the modality of treatment they
      receive. The descriptive cross-sectional study was conducted during the period of
      January 2014 to December 2015. The study was carried out among 310 purposively
      selected children attended at Pediatric Outpatient department of Community Based
      Medical College Hospital, Bangladesh. Data were collected by face to face
      interview of the parents and clinical examination and anthropometric measurement
      of children using case record form. Mean age of the children was 4.11 years with
      a SD of 4.35 years, male-female ratio was 1.25:1 with predominance 201(64.84%) of
      under-five children. The common diseases were 121(39.03%) with Acute Respiratory
      Infections (ARI), while 43(13.87%) diarrheal diseases, 25(8.06%) each with
      bronchial asthma and helminthiasis. Other diseases 96(30.97%) include anemia
      17(5.48%), urinary tract infection 15 (4.84%), peptic ulcer disease 9(2.90%),
      enteric fever, oral candidiasis, apthous ulcer of mouth, scabies and
      vulvovaginitis. Average number of children per family was 2.2 including
      251(80.97%) children having sanitary latrine in the family, 297(95.81%) with safe
      drinking water facilities and 270(87.10%) were fully vaccinated under EPI. More
      than three fourth 76(24.52%) of the children were underweight, 114(36.77%) were
      from poor families and 136(43.87%) lived in Kancha house. With the improvement of
      safe water supply and use of sanitary latrine diseases like diarrhoeal disease
      and helminthiasis are showing a decreasing trend.

PMID- 29208877
TI  - Significance of Age-Spleen-Platelet Ratio Index (ASPRI) to Exclude Cirrhosis in
      Patients with Chronic Hepatitis B.
AB  - Liver biopsy is an integral part of management of patients with Chronic Hepatitis
      B (CHB), which is helpful in confirming diagnosis, assessing grade of
      inflammation and stage of fibrosis and also in guiding treatment strategy.
      Although liver biopsy is relatively safe, morbidity occurs in 0.2-2% of patients.
      Hence various non-invasive markers, like AST-ALT Ratio (AAR), Age-Platelet Index
      (API), AST to Platelet Ratio Index (APRI), Fibroscan etc. have been developed
      worldwide to asses liver histology. Age-Spleen-Platelet Ratio Index (ASPRI) is
      new in this series. In this cross sectional study 51 (fifty one) patients with
      CHB, attending at Hepatology ward in Bangabandhu Sheikh Mujib Medical University,
      Dhaka, from January 2006 to May 2006, were studied. They were divided into two
      groups: Group I patients with ASPRI<5 and Group II patients with ASPRI>5.
      Clinical, serological, biochemical, virological parameters were analyzed and
      following liver biopsy, correlation of liver fibrosis with ASPRI was evaluated.
      Among 51 patients of CHB, 30 patients Group I with ASPRI<5 (mean 3.4) had mean
      fibrosis 1.3 using Knodell scoring system; while mean age, spleen size and
      platelet count were 23.2 years, 8.6cm and 278?109/L accordingly. In Group II, 21
      patients with ASPRI>5 (mean 5.8) had mean fibrosis 1.8; mean age was 30.6 years,
      spleen size 9.5cm and platelet count 195?109/L. Mean liver fibrosis was
      significantly increased in Group II patients. In Group I patients, liver fibrosis
      showed significant correlation with platelet count (p=0.03) and ASPRI (p= 0.011),
      while none was observed in Group II patients. Age-Spleen-Platelet Ratio Index
      ASPRI can be used as a good tool for diagnosis of liver fibrosis in chronic
      hepatitis B. However, further study with larger study population is required to
      assess its validity.

PMID- 29208878
TI  - Study of Thyroid Disorders among Type 2 Diabetic Patients Attending a Tertiary
      Care Hospital.
AB  - Type 2 diabetes mellitus (T2DM) and thyroid disorders (TD) are the two most
      common endocrine disorders in clinical practice. Unrecognized thyroid disorders
      may adversely affect the metabolic control and add more risk to an already
      predisposing type 2 diabetes mellitus. The objective of the study is to find out
      the percentage of hypothyroidism and hyperthyroidism in patients with type 2
      diabetes mellitus and non diabetic subjects. This cross-sectional study was
      conducted in the department of Biochemistry and outpatient Department of
      Endocrinology, BIRDEM General Hospital, Dhaka, Bangladesh from July 2014 to June
      2015. Total 200 patients were selected by inclusion and exclusion criteria. Among
      them, 115 were T2DM subjects and 85 were non diabetic subjects. Type 2 diabetes
      mellitus and normoglycemia were diagnosed according to WHO criteria from previous
      medical records. All patients were underwent thyroid function tests; free
      thyroxine (FT4), free tri-iodothyronine (FT3) and S. TSH (thyroid stimulating
      hormone). Study sample were divided 4 groups: Group 1: Type 2 diabetic subjects
      with thyroid disorders; Group 2: Non diabetic subjects with thyroid disorders;
      Group 3: Type 2 diabetic subjects without thyroid disorders; Group 4: Non
      diabetic without thyroid disorders. Thyroid disorders were categorized into
      subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and
      overt hyperthyroidism. Percentage of thyroid disorders in type 2 diabetes
      mellitus and non diabetic patients were estimated. Comparison of all demographic
      characteristics was done among the groups. The percentage of thyroid disorders in
      type 2 diabetic patients was 23.5%. The most frequent thyroid disorders in type 2
      diabetic patients were subclinical hypothyroidism (10.4%) and overt
      hypothyroidism (6.1%). The percentage of thyroid disorders in non diabetic
      subjects was 12%. Here, subclinical hypothyroidism is 5.9% and overt
      hypothyroidism is 3.5% were significantly higher in female, overweight and obese
      subjects. Patients with thyroid disorders (both type 2 diabetic and non-diabetic)
      had strong association with family history of thyroid disorders. This study
      showed that the percentage of thyroid disorders in type 2 diabetes mellitus is
      very high. Specially hypothyroidism (both subclinical and overt) are most
      frequent. So it is very necessary to provide regular screening for thyroid
      disorders in type 2 diabetic patients as well as initiating early treatment.
      Early treatment thyroid disorders in type 2 diabetic patients will help us to
      avoid complications and reduce morbidity and mortality of diabetes mellitus and
      thyroid disorders.

PMID- 29208879
TI  - OncoE6 Positivity among VIA Positive Suspected Cases from Colposcopy Clinic of
      Mymensingh Medical College Hospital, Mymensingh.
AB  - Cervical cancer is a major world health problem for women. It is the fourth most
      leading cause of death in women around the world. High risk HPV DNA has been
      shown to be present in 99.7% of cervical cancers worldwide. Oncoprotein E6 and E7
      play an important role in the development of cervical cancer which can be
      detected by OncoE6 cervical test. This Cross sectional observational study was
      performed to detect E6 Oncoprotein from cervical swab by OncoE6 cervical test.
      Following universal safety precautions a total of 47 endocervical swabs were
      collected from Colposcopy clinic of Obstetrics and Gynaecology department of
      Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from January
      2015 to December 2015. Laboratory work was done in the department of
      Microbiology, Mymensingh medical college. E6 strip test is an
      immunochromatographic test based on the detection of HPV-E6 oncoprotein in
      cervical swab samples. The swab specimen was treated with lysis solution and
      conditioning solution. Then the specimen solution was clarified by
      centrifugation. After that the sample solution was transferred into Detector mAb
      vial, wash solution vial and finally into developing solution vial. The test unit
      was then placed on a reading guide. Positive result was indicated by the
      appearance of purple colored test line. Out of 47 specimens 21(44.68%) were
      OncoE6 positive by OncoE6 cervical test. Among 21 positive cases 19(90.48%) were
      HPV-16 and 2 were (9.52%) HPV-18. Histopathologically out of 22 cervical
      carcinoma cases 20(90.90%) were positive by this test. Based on the findings of
      the present study, it may be concluded that screening with HPV E6 may minimize
      the overtreatment as well as the colposcopy referral. So it can be used as
      primary screening to aid colposcopy and to identify real disease. HPV based
      screening may help to control cervical cancer in Bangladesh. As HPV is a sexually
      transmitted infection; so, male screening method should be established.

PMID- 29208880
TI  - Comparative yielding of BACTEC MGIT 960 and GeneXpert MTB/RIF Assay for Rapid
      Diagnosis of Drug Resistance Tuberculosis from Sputum Specimen.
AB  - Among communicable disease, tuberculosis is the second leading cause of death
      worldwide, killing nearly two million people each year. Several diagnostic
      techniques are currently used to detect mycobacteria in respiratory specimens.
      Therefore an alternative, rapid and most effective method is required for
      diagnosis of pulmonary tuberculosis which is relatively more sensitive and
      specific. A total of 107 sputum samples of suspected TB patients were enrolled
      attending the National Tuberculosis Reference Laboratory (NTRL), Mohakhali,
      Dhaka, Bangladesh from July 2014 to July 2015. Liquid culture of 107 sputum
      samples, yielded 76.63% culture positive and 1.86% contamination was observed.
      Antibiotic susceptibility test was done for 82 culture positive sputum samples
      among which 28.04% cases were resistant to both Rifampicin and Isoniazid.
      GeneXpert assay detected 85.04% M. tuberculosis among which 25.23% were found to
      be Rifampicin Resistance.

PMID- 29208881
TI  - Clinicopathological Assessment of Colorectal Carcinoma in Mymensingh Medical
      College Hospital, Bangladesh.
AB  - Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer and the
      third leading cause of cancer death in both men and women in the US. It is mainly
      a disease of the developed countries with a western culture, yet the disease is
      not uncommon in developing countries. There is substantial geographical variation
      in the incidence and demographic characteristics of the disease. Variations are
      also observed in the risk factors, mode of presentation, sub site distribution
      and stage of the disease at presentation. This cross-sectional, descriptive study
      was intended to explore the age and sex distribution, pattern of presentation,
      sites and histological types of colorectal carcinoma. This cross-sectional,
      descriptive study was conducted in the department of surgery, Mymensingh Medical
      College Hospital, Bangladesh from October 2011 to September 2012. Purposively
      selected sixty patients irrespective of age and sex with histologically proven
      colorectal cancer were included in the study. A pre-tested, structured case
      record form was used for collection of data. Most of the patients (80.0%) were
      above 50 years of age. Mean age was 60.83 years with an SD of 11.2 years. Male to
      female ratio was almost equal (1.3:1). Positive family history was present in
      3.3% cases. More than half of the patients (53.3%) were smokers, 76.7% patients
      had the history of taking fresh fruits irregularly. Pain in abdomen was the
      leading symptom followed by alteration of bowel habit and weight loss. Anaemia
      was found in 71.6% patients followed by wasting in 70.0% cases.
      Proctosigmoidoscopy was the principal diagnostic modality (61.7%) followed by
      double contrast barium enema (30.0%). Patients with rectal growth were detected
      by digital rectal examination (23.3%). Rectum was the principal site of cancer
      (36.7%) followed by sigmoid colon (33.3%). Cancer in caecum and ascending colon
      were in 15.0% and 6.7% patients respectively. Adenocarcinoma was the principal
      histological type (88.0%) and 36.7% were well differentiated carcinoma. Majority
      of the patients (63.3%) were in advanced stage (stage III and stage IV). Some
      forms of palliative surgical treatment were offered to all colorectal cancer
      patients in the study. Postoperative outcome was uneventful in most of the
      patients. However, there was wound infection in (13.3%) patients. Colorectal
      cancer was found mainly in elderly. Male and females were affected almost
      equally. Smoking was the most commonly found risk factor. Colorectal carcinoma
      involved rectum and sigmoid colon in majority of the patients. Adenocarcinoma was
      the principal histological type and the most of which were well differentiated.
      Majority of the patients were diagnosed at an advanced stage and palliative
      treatment was offered to them. Postoperative period was uneventful in most of
      them. Policies should be taken to promote health education & screening programmes
      which will lead to early diagnosis, affordable and effective treatment and better
      prognosis.

PMID- 29208882
TI  - Thrombocytopenia in Late Onset Neonatal Sepsis and Its Relationship with Specific
      Organism in A Tertiary Care Hospital.
AB  - Late onset neonatal sepsis (LONS) is a common complication in the Neonatal
      Intensive Care Unit (NICU) especially in premature infants, in whom the clinical
      presentation can be subtle and nonspecific. Thrombocytopenia is an important
      complication of sepsis. The objective of the present study was to identify the
      organism-speci?c platelet response in neonate with culture proven LONS. In this
      retrospective study all the infants with blood culture positive LONS in the
      neonatal intensive care unit (NICU) at Square Hospitals Ltd., Dhaka, Bangladesh
      from January 2012 to June 2016 were included in this retrospective observational
      study. Multiple hemograms with platelet counts, blood culture which also revealed
      growth of fungus along with growth of bacterial organism were conducted. Duration
      of thrombocytopenia in relation to type of organism and mortality with respect to
      degree of thrombocytopenia were also studied. Out of 87 patients with culture
      proven nosocomial sepsis, 59(67.8%) patients developed thrombocytopenia (platelet
      count <150*109/l). In our study, Acinetobacter was the most frequently isolated
      organism (22/87; 25.3%) the incidence of thrombocytopenia was high among patients
      who had gram negative sepsis, concurrent bacterial and fungal sepsis (4/4, 100%)
      and also isolated fungal sepsis (11/11; 100%). The mean platelet count in Gram
      negative sepsis was significantly lower than gram positive infection (p<0.0001)
      and also in fungal sepsis in compares with gram positive bacterial causes of
      sepsis (p=0.0085). Also, the mean duration of thrombocytopenia in patients with
      Gram-positive sepsis was significantly less than that of both Gram-negative and
      fungal sepsis (p<0.0001). In this study, about 1.15% cases presented mild, 21.84%
      moderate and 36.78% severe thrombocytopenia. The mortality rate was higher in
      thrombocytopenic group. LONS sepsis is an important risk factor for
      thrombocytopenia in the NICU. Fungal and gram negative sepsis were frequently
      associated with a decreased platelet count. The mortality rate was higher in
      sepsis associated with thrombocytopenia.

PMID- 29208883
TI  - Tumor Lysis Syndrome and Hyperleukocytosis in Childhood Acute Lymphoblastic
      Leukemia in a Tertiary Care Hospital.
AB  - Acute lymphoblastic leukemia is the most common (77%) childhood leukemia and also
      the most common neoplastic disease in children. Acute lymphoblastic leukemia
      initially present with hyperleukocytosis (WBC count more than 50,000/mm3) in
      twenty percent cases. These children are particularly at risk of development of
      tumor lysis syndrome (TLS). Tumor lysis syndrome is a metabolic disorder consists
      of hyperuricaemia, hyperkalemia, hyperphosphataemia, hypocalcaemia with or
      without renal insufficiency. It is the most common disease related emergency
      encountered by physicians caring for cancer of children and adult. This cross
      sectional observational study was conducted in Department of Paediatric Haemato
      oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from
      November 2011 to April 2012 and was designed to assess early biochemical changes
      associated with hyperleukocytosis which may follow tumor lysis syndrome. Children
      with Acute lymphoblastic leukemia with hyperleukocytosis who are potential to
      develop tumor lysis syndrome were selected for the study in their initial
      presentation. Thirty patients with newly diagnosed acute lymphoblastic leukemia
      with initial high WBC count; more than 50,000/mm3 were selected for the study.
      The objectives of the study were to observe the development of tumor lysis
      syndrome with hyperleukocytosis, detection of early signs of electrolyte changes
      and early detection of tumor lysis syndrome which can help further in the
      management of such patients. Majority of the cases were in age group 7 years to
      15 years with male predominance (83%). Hyperphosphataemia (80%) followed by
      hyperuricaemia (53%) were the most common biochemical findings. Hyperkalemia and
      hypocalcaemia were present in 33% and 26% patients. Laboratory tumor lysis
      syndrome was developed in 40% of patients and clinical tumor lysis syndrome was
      developed in 20% patients with hyperleucocytosis meeting the criteria for
      definition of tumor lysis syndrome by Cairo Bishop in 2004. It was observed that
      TLS increased with higher WBC. Tumor lysis syndrome developed in 26% patients
      with WBC count below one lac, 50% with WBC count 1 lac to 2 lacs and increasing
      upto 100% with WBC count more than 3 lacs. Developing tumor lysis syndrome in
      high LDH (44% when LDH is more than 1000 unit/l) was also observed.

PMID- 29208884
TI  - Role of Oral Clonidine Premedication on Intra-operative Haemodynamics and PONV in
      Laparoscopic Cholecystectomy.
AB  - Laparoscopic cholecystectomy is a gold standard surgical procedure for
      gallbladder operation. It causes altered haemodynamic responses due to
      pneumoperitoneum and surgical procedure also causes high incidence of
      postoperative nausea &vomiting. Clonidine has been shown to reduce intraoperative
      haemodynamic instability. This randomized prospective single blind clinical study
      was designed to evaluate the efficacy of oral clonidine premedication for
      attenuation of haemodynamic responses associated with pneumoperitoneum & also
      reduce the incidence of postoperative nausea & vomiting and carried out in the
      department of Anaesthesia Analgesia and Intensive care Medicine, Bangabandhu
      Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2010 to June
      2010. Sixty adult patients of ASA physical status I & II scheduled for elective
      laparoscopic cholecystecomy were recruited for a prospective randomized single
      blind study. They were selected randomized into two equal groups, thirty in each
      group. Group A received no premedication & Group B (Clonidine) received clonidine
      (100MUgm) orally 60 minutes before induction of anaesthesia. Pulse rate, mean
      arterial pressure were recorded prior to induction, 2 minutes after endotracheal
      intubation, before pneumoperitoneum, 10 minutes & 20 minutes after
      pneumoperitoneum, 10 minutes after release of carbon dioxide & 10 minutes after
      extubation. Patients in Group B (Clonidine) maintained greater haemodynamic
      stability intraoperatively compare to Group A after intubation, during
      pneumoperitoneum and also extubation. Pulse rate & mean arterial pressure
      significantly varies in Group A compare with Group B (Clonidine) at different
      times of intraoperative period (p<0.05). Postoperative nausea & vomiting was
      significantly less in Group B (Clonidine). Premedication with oral clonidine
      attenuates the haemodynamic responses produced by pneumoperitoneum during
      laparoscopic cholecystectomy and also significantly nausea and vomiting, results
      better patient satisfaction and cost effective.

PMID- 29208885
TI  - Serum Homocysteine and its Association with Glycemic Control in Type 2 Diabetic
      Patients.
AB  - In developing countries like Bangladesh the prevalence of type 2 diabetes
      mellitus is increasing day by day. Among the long-term complications of diabetes
      mellitus, vascular complications represent a major cause of morbidity and
      mortality. Hyperglycemia is still considered the principal cause of diabetes
      complications. Total plasma homocysteine (tHcy) is an emerging cardiovascular
      risk factor. Hyperhomocysteinemia independently appears to be a stronger risk
      factor for mortality than other risk factors in type 2 diabetes than in non
      diabetes. It may partly explain the link between microalbuminurea and increased
      risk of cardiovascular disease. Objective of the study was to evaluate serum
      total homocysteine level and to correlate it with glycemic status in type 2
      diabetic patients. This cross sectional study was conducted during the period of
      July 2011 to June 2013 on 95 patients of type 2 diabetes mellitus, attending the
      Endocrine OPD of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka,
      Bangladesh. The study was carried out in the Department of Biochemistry,
      Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka, Bangladesh. Study
      subjects were selected by purposive and convenient sampling technique. Study
      subjects were categorized according to the presence or absence of
      hyperhomocysteinemia. Among the total study population hyperhomocysteinemia was
      found in 21.05%. Among them number of male was greater. Overall glycemic control
      was poor in the patients. Mean HbA1c (%) was 8.31+/-2.04. Among those having
      hyperhomocysteinemia mean HbA1c (%) was significantly lower than those who had no
      hyperhomocysteinemia (7.2+/-1.5 vs. 8.6+/-2.06). Around one fifth of the type 2
      diabetic patients had hyperhomocysteinemia. Those having hyperhomocysteinemia had
      significantly better glycemic control than those having no hyperhomocysteinemia.

PMID- 29208886
TI  - Coronary Angiography Findings and Its Determinants in Patients Presenting With
      Acute Coronary Syndrome: A Descriptive Analysis from Asian Population.
AB  - The aim was to study the angiographic profile in patients presented as acute
      coronary syndrome and its relation with risk factors and comparison between
      genders. This prospective observational study was performed on total 352 patients
      of acute coronary syndrome were analyzed for various risk factors, angiographic
      pattern in Jawaharlal Institute of Postgraduate Medical Education and Research
      (JIPMER), Puducherry, South India from January 2015 to July 2016. Mean age of
      presentation was 52.62+/-11.63 years. Male were 271(77.0%) and female were
      81(23.0%). Majority of patients were STEMI (67.6%) followed by UA (24.4%) and
      NSTEMI (8%). Smoker was 117(33.3%) patients. Hypertensive were 124(35.2%) of
      patients and 149(42.3%) were diabetics. Family history of CAD was positive in
      45(12.8%). On angiographic evaluation left main reference diameter was lower in
      females (4.02+/-0.72) than males (4.07+/-0.82). LAD was most commonly involved
      followed by RCA and LCX among all three group of acute coronary syndrome. Left
      main was least involved (8.3%). In STEMI SVD (40.3%) was most common
      presentation, after that DVD was seen in 22.3%, TVD in 10.5%, non-obstructive
      coronary was seen in 16% of patients and normal coronary was seen in 11% of
      patients. In UA 28%, 22.8%, 13.2%, 15.8%, 20.2% was seen in SVD, DVD, TVD, non
      obstructive and normal coronary respectively. Long length coronary lesions
      (>20mm) were seen in majority in all type of acute coronary syndrome. Coronary
      lesion length was not associated with presentation acute coronary syndrome and
      genders. Male were most commonly presented as acute coronary syndrome. STEMI was
      most common presentation. Diabetic was most prevalent risk factor. SVD was most
      common angiographic pattern and LAD was most common involved arteries.

PMID- 29208887
TI  - A Rare Case of Polycystic Disease of the Pancreas.
AB  - Polycystic disease of the pancreas is very rare and only few cases have been
      reported in the literature. We report a case of 27 year old female presented with
      recurrent upper abdominal pain associated with nausea and vomiting. Her
      ultrasonography of whole abdomen and computed tomography (CT) scan revealed
      polycystic pancreas associated with hepatic cysts. She underwent distal
      pancreatectomy with splenectomy. Histological examination revealed typical
      features of polycystic pancreatic disease in the resected specimen. Previously
      two of her sisters and her mother were also diagnosed as cases of polycystic
      pancreatic disease and they all underwent operative treatments. Among them one of
      those sisters and her mother received treatment under our department in 2009 and
      2014 accordingly.

PMID- 29208888
TI  - Polyarthritis is a Rare Manifestation of Pachydermoperiostosis: A Case Report.
AB  - Pachydermoperiostosis or primary hypertrophic osteoarthropathy, also known as
      Touraine-Solente-Gole syndrome, is a rare process, frequently inherited. In its
      complete form it is characterized by pachydermia (thickening of the skin),
      skeletal changes (periostosis) and acropachia (digital clubbing). Diagnosis can
      be made considering the typical clinical features and the histological feature.
      We report a patient of 25-year old man presented with joint pain involving in
      multiple joints for last 7 years and progressive enlargement of his hands and
      feet with profuse sweating of palms and soles for last 4 years. Physical
      examination revealed thickened skin with excessive furrowing of his forehead,
      dropping of both eyelids, clubbing of all fingers, toes and enlargement of his
      hands and feet with pamoplantar hyperhidrosis. Laboratory investigation shows
      raised CRP, X-ray feet lateral view showed normal heel pad thickness, new bone
      formation and periosteal elevation in lower end of tibia and fibula and skin
      biopsy showed dense fibrocollagenous tissue in dermis and subcutis and mild
      acanthosis. With this scenario he was diagnosed as primary hypertrophic
      osteoarthropathy (Pachydermoperiostosis). After diagnosis he was treated with
      cholchicine (0.6mg) twice daily, naproxen (500mg) twice daily, and risedronate
      (150mg) monthly. After one year his skin texture became less thickened, joint
      pain improved, there was no further enlargement of acral part of fore arm. In
      this report we review the characteristic features of this syndrome. We highlight
      the importance of ruling out secondary forms of hypertrophic osteoarthropathy and
      of a close follow-up of these patients because of complications that might
      develop on long-term. Although no treatment was satisfactory, we wanted to
      emphasize that NSAIDs, Cholchicine and risedronate could be an effective
      treatment option.

PMID- 29208889
TI  - Why Abortion is Illegal? Comparison of Legal and Illegal Abortion: A Critical
      Review.
AB  - Abortion is the termination of pregnancy that occurs spontaneously or purposely.
      In the most developed world, abortion is legally allowed for women seeking safe
      termination of pregnancies. Particularly, when access to legal abortion is
      restricted, abortion is the resort to unsafe methods. The aim of this review is
      to necessitate safe abortion and to accentuate the consequences of illegal
      abortion in case of legal prohibition. We used Pubmed, MedLine and Scopus
      databases to review previous literatures of safe, unsafe, legal and illegal
      abortions. Research work and reports from organizations such as World Health
      Organization (WHO), World Bank (WB) and United Nations (UN) were included.
      Snowball sampling was used to obtain relevant journals. Abortion is conventional
      whether it is safe, unsafe, legal or illegal. The intention of the antiabortion
      policy was to reduce the number of abortions globally. However, instead of
      decreasing rates, evidences show significant increase in abortions. When abortion
      is legal, the preconditions to be ensured are availability, accessibility,
      affordability and acceptability for the safe abortion facilities. When abortion
      is illegal, risk reduction strategies are needed to decrease maternal morbidity
      and mortality. We can reduce abortion related morbidity and mortality, whether it
      is legal or illegal if we can ensure the appropriate access to health care,
      including abortion services, education on sexuality, access to contraceptives,
      post abortion care, and suitable interventions and liberalization of laws. The
      paper reviewed the Mexico City Policy and the US foreign aid strategies and
      highlighted the evidence based analysis for policy reform. The liberalized
      abortion law can save pregnant women from abortion related complications and
      death.

PMID- 29208890
TI  - Impact-induced changes in source depth and volume of magmatism on Mercury and
      their observational signatures.
AB  - Mercury's crust is mostly the result of partial melting in the mantle associated
      with solid-state convection. Large impacts induce additional melting by
      generating subsurface thermal anomalies. By numerically investigating the
      geodynamical effects of impacts, here we show that impact-generated thermal
      anomalies interact with the underlying convection modifying the source depth of
      melt and inducing volcanism that can significantly postdate the impact depending
      on the impact time and location with respect to the underlying convection
      pattern. We can reproduce the volume and time of emplacement of the melt sheets
      in the interior of Caloris and Rembrandt if at about 3.7-3.8 Ga convection in the
      mantle of Mercury was weak, an inference corroborated by the dating of the
      youngest large volcanic provinces. The source depth of the melt sheets is located
      in the stagnant lid, a volume of the mantle that never participated in convection
      and may contain pristine mantle material.

PMID- 29208891
TI  - Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic
      D-cycloserine.
AB  - D-cycloserine is an antibiotic which targets sequential bacterial cell wall
      peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine
      ligase. By a combination of structural, chemical and mechanistic studies here we
      show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D
      cycloserine proceeds via a distinct phosphorylated form of the drug. This
      mechanistic insight reveals a bimodal mechanism of action for a single antibiotic
      on different enzyme targets and has significance for the design of future
      inhibitor molecules based on this chemical structure.

PMID- 29208892
TI  - Discrete and continuous mechanisms of temporal selection in rapid visual streams.
AB  - Humans can reliably detect a target picture even when tens of images are flashed
      every second. Here we use magnetoencephalography to dissect the neural mechanisms
      underlying the dynamics of temporal selection during a rapid serial visual
      presentation task. Multivariate decoding algorithms allow us to track the
      overlapping brain responses induced by each image in a rapid visual stream. The
      results show that temporal selection involves a sequence of gradual followed by
      all-or-none stages: (i) all images first undergo the same parallel processing
      pipeline; (ii) starting around 150 ms, responses to multiple images surrounding
      the target are continuously amplified in ventral visual areas; (iii) only the
      images that are subsequently reported elicit late all-or-none activations in
      visual and parietal areas around 350 ms. Thus, multiple images can cohabit in the
      brain and undergo efficient parallel processing, but temporal selection also
      isolates a single one for amplification and report.

PMID- 29208893
TI  - Geochemical and mineralogical evidence that Rodinian assembly was unique.
AB  - The mineralogy and geochemistry associated with Rodinian assembly (~1.3-0.9 Ga)
      are significantly different from those of other supercontinents. Compared to
      other supercontinents, relatively more Nb-bearing minerals, Y-bearing minerals,
      and zircons formed during Rodinian assembly, with corresponding enrichments of
      Nb, Y, and Zr concentrations in igneous rocks. By contrast, minerals bearing many
      other elements (e.g., Ni, Co, Au, Se, and platinum group elements) are
      significantly less abundant, without corresponding depletion of Ni and Co
      concentrations in igneous rocks. Here we suggest that the Nb, Y, and Zr
      enrichments in igneous rocks and relatively more occurrences of corresponding Nb
      bearing minerals, Y-bearing minerals, and zircons result from significant non-arc
      magmatism during the mid-Proterozoic, while fewer occurrences of many other
      minerals suggest enhanced erosion of Rodinian volcanic arcs and orogens. The
      prolonged, extrovert assembly of Rodinia from thickened mid-Proterozoic
      continental crust via two-sided subduction can account for both the prevalence of
      non-arc magmatism and the enhanced erosion.

PMID- 29208894
TI  - Broad modulus range nanomechanical mapping by magnetic-drive soft probes.
AB  - Stiffness matching between the probe and deformed portion of the sample in piezo
      drive peak force modulation atomic force microscopy (AFM) limits the modulus
      measurement range of single probes. Here we develop a magnetic drive peak force
      modulation AFM to broaden the dynamic range of the probe with direct cantilever
      excitation. This approach not only successfully drives the softest commercial
      probe (6 pN nm-1) for mapping extremely soft samples in liquid but also provides
      an indentation force of hundreds of nanonewtons for stiff samples with a soft
      probe. Features of direct measurements of the indentation force and depth can
      unify the elastic modulus range up to four orders of magnitude, from 1 kPa to 10
      MPa (in liquid) and 1 MPa to 20 GPa (in air or liquid) using a single probe. This
      approach can be particularly useful for analysing heterogeneous samples with
      large elastic modulus variations in multi-environments.

PMID- 29208895
TI  - Existence of multi-radical and closed-shell semiconducting states in post
      graphene organic Dirac materials.
AB  - Post-graphene organic Dirac (PGOD) materials are ordered two-dimensional networks
      of triply bonded sp 2 carbon nodes spaced by pi-conjugated linkers. PGOD
      materials are natural chemical extensions of graphene that promise to have an
      enhanced range of properties and applications. Experimentally realised molecules
      based on two PGOD nodes exhibit a bi-stable closed-shell/multi-radical character
      that can be understood through competing Lewis resonance forms. Here, following
      the same rationale, we predict that similar states should be accessible in PGOD
      materials, which we confirm using accurate density functional theory
      calculations. Although for graphene the semimetallic state is always dominant,
      for PGOD materials this state becomes marginally meta-stable relative to open
      shell multi-radical and/or closed-shell states that are stabilised through
      symmetry breaking, in line with analogous molecular systems. These latter states
      are semiconducting, increasing the potential use of PGOD materials as highly
      tuneable platforms for future organic nano-electronics and spintronics.

PMID- 29208897
TI  - Network dynamics-based cancer panel stratification for systemic prediction of
      anticancer drug response.
AB  - Cancer is a complex disease involving multiple genomic alterations that disrupt
      the dynamic response of signaling networks. The heterogeneous nature of cancer,
      which results in highly variable drug response, is a major obstacle to developing
      effective cancer therapy. Previous studies of cancer therapeutic response mostly
      focus on static analysis of genome-wide alterations, thus they are unable to
      unravel the dynamic, network-specific origin of variation. Here we present a
      network dynamics-based approach to integrate cancer genomics with dynamics of
      biological network for drug response prediction and design of drug combination.
      We select the p53 network as an example and analyze its cancer-specific state
      transition dynamics under distinct anticancer drug treatments by attractor
      landscape analysis. Our results not only enable stratification of cancer into
      distinct drug response groups, but also reveal network-specific drug targets that
      maximize p53 network-mediated cell death, providing a basis to design
      combinatorial therapeutic strategies for distinct cancer genomic subtypes.

PMID- 29208896
TI  - Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle
      checkpoint silencing.
AB  - The spindle checkpoint maintains genomic stability and prevents aneuploidy.
      Unattached kinetochores convert the latent open conformer of the checkpoint
      protein Mad2 (O-Mad2) to the active closed conformer (C-Mad2), bound to Cdc20. C
      Mad2-Cdc20 is incorporated into the mitotic checkpoint complex (MCC), which
      inhibits the anaphase-promoting complex/cyclosome (APC/C). The C-Mad2-binding
      protein p31comet and the ATPase TRIP13 promote MCC disassembly and checkpoint
      silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show
      that TRIP13 and p31comet catalyze the conversion of C-Mad2 to O-Mad2, without
      disrupting its stably folded core. We determine the crystal structure of human
      TRIP13, and identify functional TRIP13 residues that mediate p31comet-Mad2
      binding and couple ATP hydrolysis to local unfolding of Mad2. TRIP13 and p31comet
      prevent APC/C inhibition by MCC components, but cannot reactivate APC/C already
      bound to MCC. Therefore, TRIP13-p31comet intercepts and disassembles free MCC not
      bound to APC/C through mediating the local unfolding of the Mad2 C-terminal
      region.

PMID- 29208898
TI  - Diffusion of treatment in social networks and mass drug administration.
AB  - Information, behaviors, and technologies spread when people interact.
      Understanding these interactions is critical for achieving the greatest diffusion
      of public interventions. Yet, little is known about the performance of starting
      points (seed nodes) for diffusion. We track routine mass drug administration-the
      large-scale distribution of deworming drugs-in Uganda. We observe friendship
      networks, socioeconomic factors, and treatment delivery outcomes for 16,357
      individuals in 3491 households of 17 rural villages. Each village has two
      community medicine distributors (CMDs), who are the seed nodes and responsible
      for administering treatments. Here, we show that CMDs with tightly knit
      (clustered) friendship connections achieve the greatest reach and speed of
      treatment coverage. Importantly, we demonstrate that clustering predicts
      diffusion through social networks when spreading relies on contact with seed
      nodes while centrality is unrelated to diffusion. Clustering should be considered
      when selecting seed nodes for large-scale treatment campaigns.

PMID- 29208900
TI  - 'Candidatus Liberibacter asiaticus' Accumulates inside Endoplasmic Reticulum
      Associated Vacuoles in the Gut Cells of Diaphorina citri.
AB  - Citrus greening disease known also as Huanglongbing (HLB) caused by the phloem
      limited bacterium 'Candidatus Liberibacter asiaticus' (CLas) has resulted in
      tremendous losses and the death of millions of trees worldwide. CLas is
      transmitted by the Asian citrus psyllid Diaphorina citri. The closely-related
      bacteria 'Candidatus Liberibacter solanacearum' (CLso), associated with
      vegetative disorders in carrots, is transmitted by the carrot psyllid Bactericera
      trigonica. A promising approach to prevent the transmission of these pathogens is
      to interfere with the vector-pathogen interactions, but our understanding of
      these processes is limited. It was recently reported that CLas induced changes in
      the nuclear architecture, and activated programmed cell death, in D. citri midgut
      cells. Here, we used electron and fluorescent microscopy and show that CLas
      induces the formation of endoplasmic reticulum (ER)-associated bodies. The
      bacterium recruits those ER structures into Liberibacter containing vacuoles
      (LCVs), in which bacterial cells seem to propagate. ER- associated LCV formation
      was unique to CLas, as we could not detect these bodies in B. trigonica infected
      with CLso. ER recruitment is hypothesized to generate a safe replicative body to
      escape cellular immune responses in the insect gut. Understanding the molecular
      interactions that undelay these responses will open new opportunities for
      controlling CLas.

PMID- 29208899
TI  - In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects
      abnormalities of ovarian failure.
AB  - Safe clinical hormone replacement (HR) will likely become increasingly important
      in the growing populations of aged women and cancer patients undergoing
      treatments that ablate the ovaries. Cell-based HRT (cHRT) is an alternative
      approach that may allow certain physiological outcomes to be achieved with lower
      circulating hormone levels than pharmacological means due to participation of
      cells in the hypothalamus-pituitary-ovary feedback control loop. Here we describe
      the in vivo performance of 3D bioengineered ovarian constructs that recapitulate
      native cell-cell interactions between ovarian granulosa and theca cells as an
      approach to cHRT. The constructs are fabricated using either Ca++ or Sr++ to
      crosslink alginate. Following implantation in ovariectomized (ovx) rats, the Sr++
      cross-linked constructs achieve stable secretion of hormones during 90 days of
      study. Further, we show these constructs with isogeneic cells to be effective in
      ameliorating adverse effects of hormone deficiency, including bone health,
      uterine health, and body composition in this rat model.

PMID- 29208901
TI  - Alternative substrate-bound conformation of bacterial solute-binding protein
      involved in the import of mammalian host glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs), constituted by repeating uronate and amino sugar
      units, are major components of mammalian extracellular matrices. Some indigenous
      and pathogenic bacteria target GAGs for colonization to and/or infection of host
      mammalian cells. In Gram-negative pathogenic Streptobacillus moniliformis, the
      solute-binding protein (Smon0123)-dependent ATP-binding cassette (ABC)
      transporter incorporates unsaturated GAG disaccharides into the cytoplasm after
      depolymerization by polysaccharide lyase. Smon0123, composed of N and C domains,
      adopts either a substrate-free open or a substrate-bound closed form by
      approaching two domains at 47 degrees  in comparison with the open form. Here we
      show an alternative 39 degrees -closed conformation of Smon0123 bound to
      unsaturated chondroitin disaccharide sulfated at the C-4 and C-6 positions of N
      acetyl-d-galactosamine residue (CDelta4S6S). In CDelta4S6S-bound Smon0123, Arg204
      and Lys210 around the two sulfate groups were located at different positions from
      those at other substrate-bound 47 degrees -closed conformations. Therefore, the
      two sulfate groups in CDelta4S6S shifted substrate-binding residue arrangements,
      causing dynamic conformational change. Smon0123 showed less affinity with
      CDelta4S6S than with non-sulfated and monosulfated substrates. ATPase activity of
      the Smon0123-dependent ABC transporter in the presence of CDelta4S6S was lower
      than that in the presence of other unsaturated chondroitin disaccharides,
      suggesting that CDelta4S6S-bound Smon0123 was unpreferable for docking with the
      ABC transporter.

PMID- 29208902
TI  - Publisher Correction: Population scale data reveals the antidepressant effects of
      ketamine and other therapeutics approved for non-psychiatric indications.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29208903
TI  - A novel bioreactor system for biaxial mechanical loading enhances the properties
      of tissue-engineered human cartilage.
AB  - The ex vivo engineering of autologous cartilage tissues has the potential to
      revolutionize the clinical management of joint disorders. Yet, high manufacturing
      costs and variable outcomes associated with tissue-engineered implants are still
      limiting their application. To improve clinical outcomes and facilitate a wider
      use of engineered tissues, automated bioreactor systems capable of enhancing and
      monitoring neotissues are required. Here, we developed an innovative system
      capable of applying precise uni- or biaxial mechanical stimulation to developing
      cartilage neotissues in a tightly controlled and automated fashion. The
      bioreactor allows for simple control over the loading parameters with a user
      friendly graphical interface and is equipped with a load cell for monitoring
      tissue maturation. Applying our bioreactor, we demonstrate that human articular
      chondrocytes encapsulated in hydrogels composed of gelatin methacryloyl (GelMA)
      and hyaluronic acid methacrylate (HAMA) respond to uni- and biaxial mechanical
      stimulation by upregulation of hyaline cartilage-specific marker genes. We
      further demonstrate that intermittent biaxial mechanostimulation enhances
      accumulation of hyaline cartilage-specific extracellular matrix. Our study
      underlines the stimulatory effects of mechanical loading on the biosynthetic
      activity of human chondrocytes in engineered constructs and the need for easy-to
      use, automated bioreactor systems in cartilage tissue engineering.

PMID- 29208904
TI  - Author Correction: Developing a molecular picture of soil organic matter-mineral
      interactions by quantifying organo-mineral binding.
AB  - In the original version of this Article, the Acknowledgements section omitted the
      Department of Energy-funded Environmental and Molecular Sciences Laboratory in
      which the XRD measurements were performed. This error has now been corrected in
      both the PDF and HTML versions of the Article.

PMID- 29208905
TI  - Total synthesis of the reported structure of 13a-hydroxytylophorine.
AB  - The first total synthesis of the reported structure of 13a-hydroxytylophorine was
      accomplished. The key step was an unprecedented NaBH4-promoted one-pot reductive
      cyclization cascade that efficiently yielded a hydroxyl azonane intermediate. The
      indolizidine framework was obtained by means of oxidation and a subsequent
      unexpected protecting-group migration. This total synthesis revealed that the
      reported structure of the naturally isolated compound is incorrect.

PMID- 29208906
TI  - Simultaneous multi-slice inverse imaging of the human brain.
AB  - Ultrafast functional magnetic resonance imaging (fMRI) can measure blood oxygen
      level dependent (BOLD) signals with high sensitivity and specificity. Here we
      propose a novel method: simultaneous multi-slice inverse imaging (SMS-InI) - a
      combination of simultaneous multi-slice excitation, simultaneous echo refocusing
      (SER), blipped controlled aliasing in parallel imaging echo-planar imaging (EPI),
      and regularized image reconstruction. Using a 32-channel head coil array on a 3 T
      scanner, SMS-InI achieves nominal isotropic 5-mm spatial resolution and 10 Hz
      sampling rate at the whole-brain level. Compared with traditional inverse
      imaging, we found that SMS-InI has higher spatial resolution with lower signal
      leakage and higher time-domain signal-to-noise ratio with the optimized
      regularization parameter in the reconstruction. SMS-InI achieved higher effective
      resolution and higher detection power in detecting visual cortex activity than
      InI. SMS-InI also detected subcortical fMRI signals with the similar sensitivity
      and localization accuracy like EPI. The spatiotemporal resolution of SMS-InI was
      used to reveal that presenting visual stimuli with 0.2 s latency between left and
      right visual hemifield led to 0.2 s relative hemodynamic response latency between
      the left and right visual cortices. Together, these results indicate that SMS-InI
      is a useful tool in measuring cortical and subcortical hemodynamic responses with
      high spatiotemporal resolution.

PMID- 29208907
TI  - Connectivity motifs of inhibitory neurons in the mouse Auditory Cortex.
AB  - Connectivity determines the function of neural circuits and it is the gateway to
      behavioral output. The emergent properties of the Auditory Cortex (ACx) have been
      difficult to unravel partly due to our assumption that it is organized similarly
      to other sensory areas. But detailed investigations of its functional
      connectivity have begun to reveal significant differences from other cortical
      areas that perform different functions. Using Laser Scanning Photostimulation we
      previously discovered unique circuit features in the ACx. Specifically, we found
      that the functional asymmetry of the ACx (tonotopy and isofrequency axes) is
      reflected in the local circuitry of excitatory inputs to Layer 3 pyramidal
      neurons. In the present study we extend the functional wiring diagram of the ACx
      with an investigation of the connectivity patterns of inhibitory subclasses. We
      compared excitatory input to parvalbumin (PV) and somatostatin (SOM)-expressing
      interneurons and found distinct circuit-motifs between and within these
      subpopulations. Moreover, these connectivity motifs emerged as intrinsic
      differences between the left and right ACx. Our results support a functional
      circuit based approach to understand the role of inhibitory neurons in auditory
      processing.

PMID- 29208908
TI  - Multiplex three-dimensional optical mapping of tumor immune microenvironment.
AB  - Recent developments in optical tissue clearing and microscopic imaging have
      advanced three-dimensional (3D) visualization of intact tissues and organs at
      high resolution. However, to expand applications to oncology, critical
      limitations of current methods must be addressed. Here we describe transparent
      tissue tomography (T3) as a tool for rapid, three-dimensional, multiplexed
      immunofluorescent tumor imaging. Cutting tumors into sub-millimeter macrosections
      enables simple and rapid immunofluorescence staining, optical clearing, and
      confocal microscope imaging. Registering and fusing macrosection images yields
      high resolution 3D maps of multiple tumor microenvironment components and
      biomarkers throughout a tumor. The 3D maps can be quantitatively evaluated by
      automated image analysis. As an application of T3, 3D mapping and analysis
      revealed a heterogeneous distribution of programmed death-ligand 1 (PD-L1) in
      Her2 transgenic mouse mammary tumors, with high expression limited to tumor cells
      at the periphery and to CD31+ vascular endothelium in the core. Also, strong
      spatial correlation between CD45+ immune cell distribution and PD-L1 expression
      was revealed by T3 analysis of the whole tumors. Our results demonstrate that a
      tomographic approach offers simple and rapid access to high-resolution three
      dimensional maps of the tumor immune microenvironment, offering a new tool to
      examine tumor heterogeneity.

PMID- 29208910
TI  - Author Correction: Temperature dependence of protein-water interactions in a
      gated yeast aquaporin.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29208909
TI  - Mitochondrial DNA Mutations Associated with Type 2 Diabetes Mellitus in Chinese
      Uyghur Population.
AB  - A hospital-based case-control study was conducted to investigate potential
      association between mitochondrial DNA and Type 2 diabetes mellitus (T2DM) in
      Chinese Uyghur population. We sequenced mitochondrial DNA from 210 Uyghur
      individuals including 88 T2DM patients and 122 controls. Using haplogroup
      classification and association test, we found that haplogroup H (odds ratio [OR]
      = 1.40; 95% confidence interval [CI]: 1.20-1.64; P = 0.0005138) and D4 (odds
      ratio = 1.47; 95% CI: 1.22-1.77; P = 0.001064) were associated with an increased
      risk of T2DM in Chinese Uyghur population. Two markers of haplogroup D4 and H, MT
      ATP8 m.8414 T > G (p.Leu17Phe) and m.2706 G > A encoding 16S rRNA in
      mitochondria, were predicted to affect the structure of MT-ATP8 and 16S RNA,
      respectively, and may be involved in the pathogenesis of T2DM. Our study provides
      a new clue for mitochondrial DNA in the etiology of T2DM in Chinese Uyghur
      population.

PMID- 29208911
TI  - Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in
      response to antigen binding.
AB  - Proline cis-trans isomerisation is a regulatory mechanism used in a range of
      biological processes, and is related to various diseases such as Alzheimers
      disease and cancer. However, the details of the exact molecular mechanism by
      which it occurs are not known. Using X-ray crystallography, proline isomerisation
      has been shown to occur following formation of an antigen-antibody complex
      between the target epiregulin (EPR) and the antibody 9E5, at proline (Pro103),
      located in the third complementarity-determining region (CDR) of the heavy chain
      of 9E5. To obtain an accurate description of the pathway involved in cis-trans
      isomerisation in this system, we performed ten independent long molecular
      dynamics (MD) simulations starting at a stable transient bound structure obtained
      from many short binding MD simulations. As a result, we were able to describe the
      process by which cis-trans isomerisation is initiated, and suggest a catalysis
      mechanism for cis-trans isomerization in this antigen-antibody system. We found
      that Asp102, which is immediately adjacent to Pro103, rotates while changing its
      interacting partner residues in the light chain of 9E5, and at the same time EPR
      polar residues help to stabilise the intermediate states in the isomerisation
      process by interacting strongly with Asp102.

PMID- 29208912
TI  - Single electron-photon pair creation from a single polarization-entangled photon
      pair.
AB  - Quantum entanglement between different forms of qubits is an indication of the
      universality of quantum mechanics. Entanglement transfer between light and
      matter, especially photon and spin, has long been studied as the central concept,
      but it remains technically challenging for single photons and spins. In this
      paper, we show paired generation of a single electron in a GaAs quantum dot and a
      single photon from a single polarization-entangled photon pair. We measure
      temporal coincidence between the single photo-electron detection and the single
      photon detection. Considering a single photon polarization is converted to an
      electron spin via an optical selection rule, the present result indicates the
      capability of photon to spin entanglement transfer. This may be useful to explore
      the physics of entanglement transfer and also for applications to quantum
      teleportation based quantum communication.

PMID- 29208913
TI  - Prevention and treatment strategies for contextual overgeneralization.
AB  - At the core of anxiety disorders lies the tendency to generalize fear from a
      threatening to a safe situation. A deeper understanding of the mechanisms that
      facilitate and restrain generalization in humans is therefore needed. Rodent
      studies showed that pre-exposure to a context that is similar to the threatening
      context enhanced generalization to the similar context. In Experiment 1 we
      replicated these animal findings in humans (US-expectancy). Studies on the
      underlying mechanisms showed that the pre-exposure representation was recalled
      during conditioning (due to similarity between the contexts) and the shock also
      became linked to the recalled representation, resulting in greater
      generalization. In Experiment 2 we developed a pre-exposure procedure that
      increased the ability to distinguish between the conditioned and pre-exposure
      contexts, such that presentation of the former would no longer result in recall
      of the latter. We then observed that overgeneralization (US-expectancy) was
      prevented. Pre-exposure did not affect generalization of skin conductance
      response or fear potentiated startle. Finally, exploratory analyses revealed that
      increased generalization (US-expectancy), if not prevented, could be reduced by a
      reminder of the conditioned context. Hence, we developed a prevention- and a
      treatment-strategy for overgeneralization. These findings may guide the
      development of new therapeutic strategies.

PMID- 29208914
TI  - Chemical profiling and quantification of XueBiJing injection, a systematic
      quality control strategy using UHPLC-Q Exactive hybrid quadrupole-orbitrap high
      resolution mass spectrometry.
AB  - To clarify and quantify the chemical profiling of XueBiJing injection (XBJ)
      rapidly, a feasible and accurate strategy was developed by applying ultra high
      performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high
      resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS). A total of 162
      components were characterized, including 19 phenanthrenequinones, 33 lactones, 28
      flavonoids and 12 phenolic acids and 51 other compounds. Among them, 38 major
      compounds were unambiguously quantified by comparing with reference standards.
      Meanwhile, 38 representative compounds were simultaneously detected in XBJ
      samples by Q-Orbitrap HRMS. Satisfactory linearity and correlation coefficient
      were achieved with wide linear range. The precisions, repeatability, stability
      and recovery were meeting requirements. The validated method was successfully
      applied for simultaneous determination of 38 bioactive compounds in 10 batches
      XBJ samples. In addition, the similarity evaluation of fingerprintings was
      applied to assess the quality of XBJ. And the results were evaluated by multiple
      statistical strategies and five compounds might be the most important chemical
      markers for chemical quality control of XBJ. Finally, a rapid and simple UPLC
      MS/MS method was developed for determination of five markers in XBJ sample. This
      research established a high sensitive and efficient strategy for integrating
      quality control, including identification and quantification of XBJ.

PMID- 29208915
TI  - Publisher Correction: Autonomic versus perceptual accounts for tactile
      hypersensitivity in autism spectrum disorder.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29208916
TI  - Sumatran tiger survival threatened by deforestation despite increasing densities
      in parks.
AB  - The continuing development of improved capture-recapture (CR) modeling techniques
      used to study apex predators has also limited robust temporal and cross-site
      analyses due to different methods employed. We develop an approach to standardize
      older non-spatial CR and newer spatial CR density estimates and examine trends
      for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta
      regression of 17 existing densities and new estimates from our own fieldwork. We
      find that tiger densities were 47% higher in primary versus degraded forests and,
      unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a
      recovery from earlier poaching. However, while tiger numbers may have temporarily
      risen, the total potential island-wide population declined by 16.6% from 2000 to
      2012 due to forest loss and degradation and subpopulations are significantly more
      fragmented. Thus, despite increasing densities in smaller parks, we conclude that
      there are only two robust populations left with >30 breeding females, indicating
      Sumatran tigers still face a high risk of extinction unless deforestation can be
      controlled.

PMID- 29208917
TI  - Correspondence: Reply to 'Phantom phonon localization in relaxors'.

PMID- 29208918
TI  - The necessity to choose causes the effects of reward on saccade preparation.
AB  - When humans have to choose between different options, they can maximize their
      payoff by choosing the option that yields the highest reward. Information about
      reward is not only used to optimize decisions but also for movement preparation
      to minimize reaction times to rewarded targets. Here, we show that this is
      especially true in contexts in which participants additionally have to choose
      between different options. We probed eye movement preparation by measuring
      saccade latencies to differently rewarded single targets (single-trial) appearing
      left or right from fixation. In choice-trials, both targets were displayed and
      participants were free to decide for one target to receive the corresponding
      reward. In blocks without choice-trials, single-trial latencies were not or only
      weakly affected by reward. With choice-trials present, the influence of reward
      increased with the proportion and difficulty of choices and decreased when a cue
      indicated that no choice will be necessary. Choices caused a delay in subsequent
      single-trial responses to the non-chosen option. Taken together, our results
      suggest that reward affects saccade preparation mainly when the outcome is
      uncertain and depends on the participants' behavior, for instance when they have
      to choose between targets differing in reward.

PMID- 29208919
TI  - Robust method for identification of prognostic gene signatures from gene
      expression profiles.
AB  - In the last decade, many attempts have been made to use gene expression profiles
      to identify prognostic genes for various types of cancer. Previous studies
      evaluating the prognostic value of genes suffered by failing to solve the
      critical problem of classifying patients into different risk groups based on
      specific gene expression threshold levels. Here, we present a novel method,
      called iterative patient partitioning (IPP), which was inspired by the receiver
      operating characteristic (ROC) curve, is based on the log-rank test and overcomes
      the threshold decision problem. We applied IPP to analyze datasets pertaining to
      various subtypes of breast cancer. Using IPP, we discovered both novel and well
      studied prognostic genes related to cell cycle/proliferation or the immune
      response. The novel genes were further analyzed using copy-number alteration and
      mutation data, and these results supported their relationship with prognosis.

PMID- 29208920
TI  - A feasibility study on non-invasive oxidative metabolism detection and acoustic
      assessment of human vocal cords by using optical technique.
AB  - Voice disorder such as vocal fatigue is a common and complex multifaceted
      clinical problem that presents a significant impact on quality of life. In this
      study, the functional near-infrared diffuse optical technique (fNIRS-DOT) was
      proposed as a novel approach for human vocal cords oxidative metabolism detection
      and acoustic assessment simultaneously to provide a multidimensional assessment
      of voice disorder. A totally of 60 healthy subjects included 30 male and 30
      female adults of age-matched were recruited and performed a vocal loading task to
      trigger a mild inflammation of the vocal cords in this study. In the results of
      oxidative metabolism, the vocal cords expressed hypoxia after vocal loading task
      in both male and female groups that could provide relevant information on the
      relationship between tissue oxygen consumption and supply for vocal cords
      diagnosis. Additionally, the results of optical acoustic assessment revealed the
      worse/changes voice quality after vocal loading task. Therefore, integration of
      non-invasive oxidative metabolism detection and acoustic assessment by using
      optical technique could provide more relevant information for diagnosis of voice
      disorders. The multi-functional vocal cords detection system could provide a good
      feasibility for clinical applications such as diagnosis and therapeutic
      monitoring of voice disorder.

PMID- 29208921
TI  - Fe4S4 Cubane Type Cluster Immobilized on a Graphene Support: A High Performance
      H2 Evolution Catalysis in Acidic Water.
AB  - The development of alternate catalysts that utilize non-precious metal based
      electrode materials such as the first row transition metal complexes is an
      important goal for economic fuel cell design. In this direction, a new Fe4S4
      cubane type cluster, [PPh4]2[Fe4S4(DMET)4] (1) (DMET = cis-1,2
      dicarbomethoxyethylene dithiolate) and its composite with functionalized
      graphene, (1@graphene) have been synthesized and characterized. The presence of
      nanocrystalline structures on graphene matrix in TEM and SEM images of 1@graphene
      indicate that the cluster (1) has been immobilized. The composite, 1@graphene
      evolves H2 gas from p-toluene sulfonic acid (TsOH) in a mixture of H2O and CH3CN
      under ambient conditions with a significant turnover number of 3200. 1@graphene
      electro-catalyzes H2 evolution at Ep, -1.2 V with remarkable throughput,
      catalytic efficiency and stability in only H2O or in only CH3CN. The Fe4S4
      cluster (1) alone electro-catalyzes hydrogen evolution at Ep, -0.75 V from TsOH
      in CH3CN. The X-ray crystal structure of the Fe4S4 cluster (1) (lambdamax,
      CH2Cl2, 823 nm; epsilon, 2200 mol-1 cm-1) shows that it is dianionic with a
      cumulative oxidation state of +2.5 for the iron centers and short C-S bond
      distances (ca., 1.712 A & 1.727 A) indicating the presence of sulfur based
      radicals.

PMID- 29208922
TI  - Beyond the Michaelis-Menten equation: Accurate and efficient estimation of enzyme
      kinetic parameters.
AB  - Examining enzyme kinetics is critical for understanding cellular systems and for
      using enzymes in industry. The Michaelis-Menten equation has been widely used for
      over a century to estimate the enzyme kinetic parameters from reaction progress
      curves of substrates, which is known as the progress curve assay. However, this
      canonical approach works in limited conditions, such as when there is a large
      excess of substrate over enzyme. Even when this condition is satisfied, the
      identifiability of parameters is not always guaranteed, and often not verifiable
      in practice. To overcome such limitations of the canonical approach for the
      progress curve assay, here we propose a Bayesian approach based on an equation
      derived with the total quasi-steady-state approximation. In contrast to the
      canonical approach, estimates obtained with this proposed approach exhibit little
      bias for any combination of enzyme and substrate concentrations. Importantly,
      unlike the canonical approach, an optimal experiment to identify parameters with
      certainty can be easily designed without any prior information. Indeed, with this
      proposed design, the kinetic parameters of diverse enzymes with disparate
      catalytic efficiencies, such as chymotrypsin, fumarase, and urease, can be
      accurately and precisely estimated from a minimal amount of timecourse data. A
      publicly accessible computational package performing such accurate and efficient
      Bayesian inference for enzyme kinetics is provided.

PMID- 29208923
TI  - Plant-endophytes interaction influences the secondary metabolism in Echinacea
      purpurea (L.) Moench: an in vitro model.
AB  - The influence of the interaction(s) between the medicinal plant Echinacea
      purpurea (L.) Moench and its endophytic communities on the production of
      alkamides is investigated. To mimic the in vivo conditions, we have set up an
      infection model of axenic in vitro E. purpurea plants inoculated with a pool of
      bacterial strains isolated from the E. purpurea stems and leaves. Here we show
      different alkamide levels between control (not-inoculated) and inoculated plants,
      suggesting that the alkamide biosynthesis may be modulated by the bacterial
      infection. Then, we have analysed the branched-chain amino acids (BCCA)
      decarboxylase gene (GenBank Accession #LT593930; the enzymatic source for the
      amine moiety formation of the alkamides) expression patterns. The expression
      profile shows a higher expression level in the inoculated E. purpurea tissues
      than in the control ones. These results suggest that the plant-endophyte
      interaction can influence plant secondary metabolism affecting the therapeutic
      properties of E. purpurea.

PMID- 29208924
TI  - HSP60 possesses a GTPase activity and mediates protein folding with HSP10.
AB  - The mammalian molecular chaperone, HSP60, plays an essential role in protein
      homeostasis through mediating protein folding and assembly. The structure and ATP
      dependent function of HSP60 has been well established in recent studies. After
      ATP, GTP is the major cellular nucleotide. In this paper, we have investigated
      the role of GTP in the activity of HSP60. It was found that HSP60 has different
      properties with respect to allostery, complex formation and protein folding
      activity depending on the nucleoside triphosphate present. The presence of GTP
      slightly affected the ATPase activity of HSP60 during protein folding. These
      results provide clues as to the functional mechanism of the HSP60-HSP10 complex.

PMID- 29208925
TI  - Feeding type and development drive the ingestion of microplastics by freshwater
      invertebrates.
AB  - Microscopic plastic items (microplastics) are ubiquitously present in aquatic
      ecosystems. With decreasing size their availability and potential to accumulate
      throughout food webs increase. However, little is known on the uptake of
      microplastics by freshwater invertebrates. To address this, we exposed species
      with different feeding strategies to 1, 10 and 90 um fluorescent polystyrene
      spheres (3-3 000 particles mL-1). Additionally, we investigated how developmental
      stages and a co-exposure to natural particles (e.g., food) modulate microplastic
      ingestion. All species ingested microplastics in a concentration-dependent manner
      with Daphnia magna consuming up to 6 180 particles h-1, followed by Chironomus
      riparius (226 particles h-1), Physella acuta (118 particles h-1), Gammarus pulex
      (10 particles h-1) and Lumbriculus variegatus (8 particles h-1). D. magna did not
      ingest 90 um microplastics whereas the other species preferred larger
      microplastics over 1 um in size. In C. riparius and D. magna, size preference
      depended on the life stage with larger specimens ingesting more and larger
      microplastics. The presence of natural particles generally reduced the
      microplastics uptake. Our results demonstrate that freshwater invertebrates have
      the capacity to ingest microplastics. However, the quantity of uptake depends on
      their feeding type and morphology as well as on the availability of
      microplastics.

PMID- 29208926
TI  - Altered expression of metabolites and proteins in wild and caged fish exposed to
      wastewater effluents in situ.
AB  - Population growth has led to increased global discharges of wastewater.
      Contaminants that are not fully removed during wastewater treatment, such as
      pharmaceuticals and personal care products (PPCPs), may negatively affect aquatic
      ecosystems. PPCPs can bioaccumulate causing adverse health effects and
      behavioural changes in exposed fish. To assess the impact of PPCPs on wild fish,
      and to assess whether caged fish could be used as a surrogate for resident wild
      fish in future monitoring, we caged goldfish in a marsh affected by discharges of
      wastewater effluents (Cootes Paradise, Lake Ontario, Canada). We collected plasma
      from resident wild goldfish, and from goldfish that we caged in the marsh for
      three weeks. We analyzed the plasma proteome and metabolome of both wild and
      caged fish. We also compared proteomic and metabolic responses in caged and wild
      fish from the marsh to fish caged at a reference site (Jordan Harbour
      Conservation Area). We identified significant changes in expression of over 250
      molecules that were related to liver necrosis, accumulation and synthesis of
      lipids, synthesis of cyclic AMP, and the quantity of intracellular calcium in
      fish from the wastewater affected marsh. Our results suggest that PPCPs could be
      affecting the health of wild fish populations.

PMID- 29208928
TI  - Finite size effect on the structural and magnetic properties of MnAs/GaAs(001)
      patterned microstructures thin films.
AB  - MnAs epitaxial thin films on GaAs(001) single crystalline substrates crystallize
      at room temperature (RT) in a mixture of two crystalline phases with distinct
      magnetic properties, organized as stripes along the MnAs [0001] direction. This
      particular morphology is driven by anisotropic epitaxial strain. We elucidate
      here the physical mechanisms at the origin of size reduction effect on the MnAs
      crystalline phase transition. We investigated the structural and magnetic changes
      in MnAs patterned microstructures (confined geometry) when the lateral dimension
      is reduced to values close to the periodicity and width of the stripes observed
      in continuous films. The effects of the microstructure's lateral size, shape and
      orientation (with respect to the MnAs [Formula: see text] direction) were
      characterized by local probe synchrotron X-ray diffraction (MU-XRD) using a
      focused X-ray beam, X-ray Magnetic Circular Dichroism - Photo Emission Electron
      Microscopy (XMCD-PEEM) and Low Energy Electron Microscopy (LEEM). Changes in the
      transition temperature and the crystalline phase distribution inside the
      microstructures are evidenced and quantitatively measured. The effect of finite
      size and strain relaxation on the magnetic domain structure is also discussed.
      Counter-intuitively, we demonstrate here that below a critical microstructure
      size, bulk MnAs structural and magnetic properties are restored. To support our
      observations we developed, tested and validated a model based on the size
      dependence of the elastic energy and strain relaxation to explain this phase re
      distribution in laterally confined geometry.

PMID- 29208927
TI  - Establishment of a strain of haemophilia-A pigs by xenografting of foetal
      testicular tissue from neonatally moribund cloned pigs.
AB  - Grafting of testicular tissue into immunodeficient mice makes it possible to
      obtain functional sperm from immature donor animals that cannot be used for
      reproduction. We have developed a porcine model of human haemophilia A
      (haemophilia-A pigs) by nuclear transfer cloning from foetal fibroblasts after
      disruption of the X-linked coagulation factor VIII (F8) gene. Despite having a
      recessive condition, female F8+/- cloned pigs died of severe bleeding at an early
      age, as was the case for male F8-/Y cloned pigs, thus making it impossible to
      obtain progeny. In this study, therefore, we produced sperm from F8-/Y cloned
      pigs by grafting their foetal testicular tissue into nude mice. Two F8+/- female
      pigs were generated from oocytes injected with xenogeneic sperm. Unlike the F8+/-
      cloned pigs, they remained asymptomatic, and delivered five F8-/Y and four F8+/-
      pigs after being crossed with wild-type boars. The descendant F8-/Y pigs
      conserved the haemophilia phenotype. Thus, the present F8+/- pigs show resolution
      of the phenotypic abnormality, and will facilitate production of F8-/Y pigs as
      founders of a strain of haemophilia-A pigs for the development of new
      therapeutics for haemophilia A. This strategy will be applicable to other
      genetically modified pigs.

PMID- 29208930
TI  - Attraction of Halyomorpha halys (Hemiptera: Pentatomidae) haplotypes in North
      America and Europe to baited traps.
AB  - Halyomorpha halys is a global invasive species, native to Southeast Asia, that is
      threatening agriculture in invaded regions. Our objectives were to: 1) establish
      the attractiveness of semiochemical stimuli paired with field-deployed traps in
      Europe (Greece, Hungary, Italy, and Switzerland), compared with Maryland, USA,
      and 2) identify H. halys haplotypes recovered from traps at each location. We
      found qualitatively identical patterns of capture between sites located across
      Europe and in Maryland, USA. In both regions, captures of H. halys adults
      indicated a synergistic response to traps baited with the two component H. halys
      aggregation pheromone, and pheromone synergist, methyl (2E, 4E, 6Z)-decatrienoate
      when compared with either individually. Haplotype diversity in Europe based on
      trapped specimens was much greater than the USA, with five new haplotypes
      described here, probably indicating ongoing invasion and re-introduction of H.
      halys. By contrast, a single, previously identified haplotype was trapped in
      Maryland, USA, representing a single introduction. All H. halys haplotypes
      responded to each semiochemical in apparent proportion to their frequency in the
      overall population based on independently derived information from prior work.
      Taken together, these data suggest that pheromone-based technology will be of
      global utility for the monitoring of this important invasive species.

PMID- 29208929
TI  - The choice of cryopreservation method affects immune compatibility of human
      cardiovascular matrices.
AB  - Conventional frozen cryopreservation (CFC) is currently the gold standard for
      cardiovascular allograft preservation. However, inflammation and structural
      deterioration limit transplant durability. Ice-free cryopreservation (IFC)
      already demonstrated matrix structure preservation combined with attenuated
      immune responses. In this study, we aim to explore the mechanisms of this
      diminished immunogenicity in vitro. First, we characterized factors released by
      human aortic tissue after CFC and IFC. Secondly, we analyzed co-cultures with
      human peripheral blood mononuclear cells, purified monocytes, T cells and
      monocyte-derived macrophages to examine functional immune effects triggered by
      the tissue or released cues. IFC tissue exhibited significantly lower metabolic
      activity and release of pro-inflammatory cytokines than CFC tissue, but
      surprisingly, more active transforming growth factor beta. Due to reduced
      cytokine release by IFC tissue, less monocyte and T cell migration was detected
      in a chemotaxis system. Moreover, only cues from CFC tissue but not from IFC
      tissue amplified alphaCD3 triggered T cell proliferation. In a specifically
      designed macrophage-tissue assay, we could show that macrophages did not
      upregulate M1 polarization markers (CD80 or HLA-DR) on either tissue type. In
      conclusion, IFC selectively modulates tissue characteristics and thereby
      attenuates immune cell attraction and activation. Therefore, IFC treatment
      creates improved opportunities for cardiovascular graft preservation.

PMID- 29208931
TI  - Novel Methods for Prevention of Hydrogen Embrittlement in Iron.
AB  - Iron is the most widely used metal in the world. However, hydrogen embrittlement
      in steels-iron based alloys-is an important issue related to the safety of our
      infrastructure, such as railroads and bridges. Therefore, the prevention of
      hydrogen embrittlement in steels is necessary. In the present study, we
      demonstrate two novel methods for the prevention of hydrogen embrittlement in
      iron: one involves the low-energy implantation of helium, which is usually an
      element harmful to metals, into iron, the other is inducing damage to the iron
      surface by ion irradiation. In general, irradiation with high-energy particles
      leads to metal brittleness. In the former method, the driving force for hydrogen
      embrittlement in iron is weakened, in the latter method, hydrogen diffusion in
      iron is prevented because of trapping of hydrogen atoms in the vacancies produced
      by the irradiation. As a result, hydrogen embrittlement in iron was suppressed by
      both methods.

PMID- 29208932
TI  - Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent
      mouse strain and progresses to cancer.
AB  - Mouse papillomavirus has shown broad tissue tropism in nude mice. Previous
      studies have tested cutaneous infections in different immunocompromised and
      immunocompetent mouse strains. In the current study, we examined mucosal
      infection in several immunocompetent and immunocompromised mouse strains. Viral
      DNA was monitored periodically by Q-PCR of lavage samples. Immunohistochemistry
      and in situ hybridization were used to determine viral capsid protein and viral
      DNA respectively. All athymic nude mouse strains showed active infections at both
      cutaneous and mucosal sites. Interestingly, NOD/SCID mice, which have a
      deficiency in T, B, and NK cells, showed minimal disease at cutaneous sites but
      developed persistent infection at the mucosal sites including those of the
      anogenital region and the oral cavity. Three strains of immunocompetent mice
      supported mucosal infections. Infections of the lower genital tract in
      heterozygous (immunocompetent) mice of the NU/J strain progressed to high grade
      dysplasia and to carcinoma in situ. Anti-MmuPV1 neutralizing antibodies were
      detected in the sera of all immunocompetent animals. Our findings demonstrate
      that the mucosae may be the preferred sites for this virus in mice. The mouse
      model is expected to be a valuable model for the study of mucosal papillomavirus
      disease, progression, and host immune control.

PMID- 29208933
TI  - The anthelmintic praziquantel is a human serotoninergic G-protein-coupled
      receptor ligand.
AB  - Schistosomiasis is a debilitating tropical disease caused by infection with
      parasitic blood flukes. Approximately 260 million people are infected worldwide,
      underscoring the clinical and socioeconomic impact of this chronic infection.
      Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the
      therapeutic mainstay for over three decades of clinical use. However, the
      molecular target(s) of PZQ remain undefined. Here we identify a molecular target
      for the antischistosomal eutomer - (R)-PZQ - which functions as a partial agonist
      of the human serotoninergic 5HT2B receptor. (R)-PZQ modulation of serotoninergic
      signaling occurs over a concentration range sufficient to regulate vascular tone
      of the mesenteric blood vessels where the adult parasites reside within their
      host. These data establish (R)-PZQ as a G-protein-coupled receptor ligand and
      suggest that the efficacy of this clinically important anthelmintic is supported
      by a broad, cross species polypharmacology with PZQ modulating signaling events
      in both host and parasite.

PMID- 29208934
TI  - Salmonella small RNA fragment Sal-1 facilitates bacterial survival in infected
      cells via suppressing iNOS induction in a microRNA manner.
AB  - Salmonella can hijack host atypical miRNA processing machinery to cleave its
      small non-coding RNA into a ~22-nt RNA fragment, Sal-1, which facilitates
      Salmonella survival in the infected host. The mechanism through which Sal-1
      promotes Salmonella survival, however, remains unknown. In the present study, we
      reported that Sal-1 targets cellular inducible nitric oxide synthase (iNOS) in a
      miRNA manner, leading to attenuation of host cell iNOS/NO-mediated anti-microbial
      capacity. First, depletion of Sal-1 in Salmonella-infected epithelial cells
      significantly increased the iNOS level but not the levels of various inflammatory
      cytokines. Bioinformatics analysis and mutagenesis strategies were consistent
      with the identification of mRNA of iNOS as a target of Sal-1 in both human and
      mice. Second, western blot and immunohistochemical analysis confirmed that Sal-1
      suppressed iNOS expression in vitro and in vivo, thus reducing the production of
      NO. Finally, Sal-1 facilitating Salmonella survival through suppressing iNOS
      induction was confirmed in mouse model by expressing mutated iNOS that is not
      targeted by Sal-1 in mice colon. In conclusion, our study provides new insight
      into the pathogenic mechanism of intracellular bacteria to modulate host innate
      immune response.

PMID- 29208935
TI  - Author Correction: The impact of poor asthma control among asthma patients
      treated with inhaled corticosteroids plus long-acting beta2-agonists in the
      United Kingdom: a cross-sectional analysis.
AB  - A correction to this article has been published and is linked from the HTML
      version of this article.

PMID- 29208936
TI  - Disulfide driven folding for a conditionally disordered protein.
AB  - Conditionally disordered proteins are either ordered or disordered depending on
      the environmental context. The substrates of the mitochondrial intermembrane
      space (IMS) oxidoreductase Mia40 are synthesized on cytosolic ribosomes and
      diffuse as intrinsically disordered proteins to the IMS, where they fold into
      their functional conformations; behaving thus as conditionally disordered
      proteins. It is not clear how the sequences of these polypeptides encode at the
      same time for their ability to adopt a folded structure and to remain unfolded.
      Here we characterize the disorder-to-order transition of a Mia40 substrate, the
      human small copper chaperone Cox17. Using an integrated real-time approach,
      including chromatography, fluorescence, CD, FTIR, SAXS, NMR, and MS analysis, we
      demonstrate that in this mitochondrial protein, the conformational switch between
      disordered and folded states is controlled by the formation of a single disulfide
      bond, both in the presence and in the absence of Mia40. We provide molecular
      details on how the folding of a conditionally disordered protein is tightly
      regulated in time and space, in such a way that the same sequence is competent
      for protein translocation and activity.

PMID- 29208937
TI  - Elucidating the in vivo interactome of HIV-1 RNA by hybridization capture and
      mass spectrometry.
AB  - HIV-1 replication requires myriad interactions between cellular proteins and the
      viral unspliced RNA. These interactions are important in archetypal RNA processes
      such as transcription and translation as well as for more specialized functions
      including alternative splicing and packaging of unspliced genomic RNA into
      virions. We present here a hybridization capture strategy for purification of
      unspliced full-length HIV RNA-protein complexes preserved in vivo by formaldehyde
      crosslinking, and coupled with mass spectrometry to identify HIV RNA-protein
      interactors in HIV-1 infected cells. One hundred eighty-nine proteins were
      identified to interact with unspliced HIV RNA including Rev and Gag/Gag-Pol, 24
      host proteins previously shown to bind segments of HIV RNA, and over 90 proteins
      previously shown to impact HIV replication. Further analysis using siRNA
      knockdown techniques against several of these proteins revealed significant
      changes to HIV expression. These results demonstrate the utility of the approach
      for the discovery of host proteins involved in HIV replication. Additionally,
      because this strategy only requires availability of 30 nucleotides of the HIV-RNA
      for hybridization with a capture oligonucleotide, it is readily applicable to any
      HIV system of interest regardless of cell type, HIV-1 virus strain, or
      experimental perturbation.

PMID- 29208939
TI  - Diet breadth modulates preference - performance relationships in a phytophagous
      insect community.
AB  - In most phytophagous insects, larvae are less mobile than adults and their
      fitness depends on the plant chosen by their mother. To maximize fitness, adult
      preference and larval performance should thus be correlated. This correlation is
      not always apparent and seems to increase with the level of specialisation, i.e.
      specialists have a stronger preference for high quality host plant species
      compared to generalists. The aim of this study was to test whether the
      relationship between female preference and larval performance was stronger for
      specialists than for generalists within a community of fruit flies (Diptera:
      Tephritidae). A total of six fruit fly species was used, including four
      generalists, and two specialists co-existing in La Reunion island (France). We
      estimated oviposition preference through the number of eggs laid and larval
      performance through the larval survival on 29 different host plants species
      belonging to 15 families in the laboratory and evaluated the relationship between
      these two traits. Preference-performance relationship differed according to the
      degree of specialisation with a strong positive correlation for specialists and
      no relationship for generalists. These results substantiate the theory that
      choosing high quality hosts is more important for specialists that are adapted to
      survive on fewer host plants than for generalists.

PMID- 29208938
TI  - Oncolytic virotherapy as an immunotherapeutic strategy for multiple myeloma.
AB  - Multiple Myeloma (MM), a clonal malignancy of antibody-producing plasma cells, is
      the second most common hematologic malignancy and results in significant patient
      morbidity and mortality. The high degree of immune dysregulation in MM, including
      T cell imbalances and up-regulation of immunosuppressive checkpoint proteins and
      myeloid derived suppressor cells, allows this malignancy to escape from host
      immune control. Despite advances in the therapeutic landscape of MM over the last
      decade, including the introduction of immunomodulatory drugs, the prognosis for
      this disease is poor, with less than 50% of patients surviving 5 years. Thus,
      novel treatment strategies are required. Oncolytic viruses (OV) are a promising
      new class of therapeutics that rely on tumour specific oncolysis and the
      generation of a potent adaptive anti-tumour immune response for efficacy. To
      date, a number of OV have shown efficacy in pre-clinical studies of MM with three
      reaching early phase clinical trials. OVs represent a rational therapeutic
      strategy for MM based on (1) their tumour tropism, (2) their ability to
      potentiate anti-tumour immunity and (3) their ability to be rationally combined
      with other immunotherapeutic agents to achieve a more robust clinical response.

PMID- 29208940
TI  - CEA but not CA19-9 is an independent prognostic factor in patients undergoing
      resection of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with
      increasing incidence but dismal prognosis. Surgical treatment has remained the
      only potentially curative treatment option, but it remains unclear which patients
      benefit most from liver surgery, highlighting the need for new preoperative
      stratification strategies. In clinical routine, CA19-9 represents the most widely
      used tumor marker in CCA patients. However, data on the prognostic value of CA19
      9 in CCA patients are limited and often inconclusive, mostly due to small cohort
      sizes. Here, we investigated the prognostic value of CA19-9 in comparison with
      other standard laboratory markers in a large cohort of CCA patients that
      underwent tumor resection. Of note, while CA19-9 and CEA were able to
      discriminate between CCA and healthy controls, CEA showed a higher accuracy for
      the differentiation between CCA and patients with primary sclerosing cholangitis
      (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C
      reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in
      Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9
      represented an independent predictor of survival in multivariate Cox-regression
      analysis. Our data suggest that CEA might help to identify CCA patients with an
      unfavourable prognosis after tumor resection.

PMID- 29208941
TI  - The Role of Backbone Hydration of Poly(N-isopropyl acrylamide) Across the Volume
      Phase Transition Compared to its Monomer.
AB  - Thermo-responsive polymers undergo a reversible coil-to-globule transition in
      water after which the chains collapse and aggregate into bigger globules when
      passing to above its lower critical solution temperature (LCST). The hydrogen
      bonding with the amide groups in the side chains has to be contrasted with the
      hydration interaction of the hydrophobic main-chain hydrocarbons. In the present
      investigation we study molecular changes in the polymer poly(N-isopropyl
      acrylamide) (PNIPAM) and in its monomer N-isopropyl acrylamide (NIPAM) in
      solution across the LCST transition. Employing Fourier-transform infrared
      spectroscopy we probe changes in conformation and hydrogen bonding. We observe a
      nearly discontinuous shift of the peak frequencies and areas of vibrational bands
      across the LCST transition for PNIPAM whereas NIPAM exhibits a continuous linear
      change with temperature. This supports the crucial role of the polymer backbone
      with respect to hydration changes in the amide group in combination with
      cooperative interactions of bound water along the backbone chain.

PMID- 29208942
TI  - Endoscope-assisted resection of nonneoplastic space-occupying lesion in oral and
      maxillofacial areas.
AB  - Endoscope-assisted oral and maxillofacial surgeries have been applied to the
      resection of tumors with minimal invasion and good cosmetic outcomes. However,
      with regard to endoscope-assisted resection of nonneoplastic space-occupying
      lesion (NSOL) in oral and maxillofacial areas which differ from tumors in
      treatment, there are no systematic reports. Therefore the advantages and
      limitations of the endoscopy-assisted approach (EAA) in resection of NSOL remain
      unclear. In this novel study we describe endoscope technique for resection of
      NSOL in face and submandibular areas and compare the feasibility and
      effectiveness of EAA with external approach (EA). Eleven patients underwent EAA
      and 20 patients underwent EA procedures. The perioperative and postoperative
      outcomes of the patients were evaluated. The resection of NSOL with EAA was
      completed successfully with a shorter hospitalization duration, less bleeding, a
      smaller incison and better satisfaction with appearance than with the EA
      procedure (P < 0.01). Our study showed that endoscope-assisted resection of NSOL
      is technically safe, feasible and practicable. Good cosmetic results with minimal
      invasion can be achieved with this new technique and therefore this may be a
      promising new standard procedure in oral and maxillofacial areas.

PMID- 29208943
TI  - Adhesion toughness of multilayer graphene films.
AB  - Interface adhesion toughness between multilayer graphene films and substrates is
      a major concern for their integration into functional devices. Results from the
      circular blister test, however, display seemingly anomalous behaviour as adhesion
      toughness depends on number of graphene layers. Here we show that interlayer
      shearing and sliding near the blister crack tip, caused by the transition from
      membrane stretching to combined bending, stretching and through-thickness
      shearing, decreases fracture mode mixity G II/G I, leading to lower adhesion
      toughness. For silicon oxide substrate and pressure loading, mode mixity
      decreases from 232% for monolayer films to 130% for multilayer films, causing the
      adhesion toughness G c to decrease from 0.424 J m-2 to 0.365 J m-2. The mode I
      and II adhesion toughnesses are found to be G Ic = 0.230 J m-2 and G IIc = 0.666
      J m-2, respectively. With point loading, mode mixity decreases from 741% for
      monolayer films to 262% for multilayer films, while the adhesion toughness G c
      decreases from 0.543 J m-2 to 0.438 J m-2.

PMID- 29208945
TI  - Safeguarding our soils.

PMID- 29208944
TI  - Correspondence: Phantom phonon localization in relaxors.

PMID- 29208947
TI  - The Y-chromosome haplogroup C3*-F3918, likely attributed to the Mongol Empire,
      can be traced to a 2500-year-old nomadic group.
AB  - The Mongol Empire had a significant role in shaping the landscape of modern
      populations. Many populations living in Eurasia may have been the product of
      population mixture between ancient Mongolians and natives following the expansion
      of Mongol Empire. Geneticists have found that most of these populations carried
      the Y-haplogroup C3* (C-M217). To trace the history of haplogroup (Hg) C3* and to
      further understand the origin and development of Mongolians, ancient human
      remains from the Jinggouzi, Chenwugou and Gangga archaeological sites, which
      belonged to the Donghu, Xianbei and Shiwei, respectively, were analysed. Our
      results show that nine of the eleven males of the Gangga site, two of the eight
      males of Chengwugou site and all of the twelve males of Jinggouzi site were found
      to have mutations at M130 (Hg C), M217 (Hg C3), L1373 (C2b, ISOGG2015), with the
      absence of mutations at M93 (Hg C3a), P39 (Hg C3b), M48 (Hg C3c), M407 (Hg C3d)
      and P62 (Hg C3f). These samples were attributed to the Y-chromosome Hg C3* (Hg
      C2b, ISOGG2015), and most of them were further typed as Hg C2b1a based on the
      mutation at F3918. Finally, we inferred that the Y-chromosome Hg C3*-F3918 can
      trace its origins to the Donghu ancient nomadic group.

PMID- 29208946
TI  - The enigmatic SAR202 cluster up close: shedding light on a globally distributed
      dark ocean lineage involved in sulfur cycling.
AB  - The dark ocean microbiota represents the unknown majority in the global ocean
      waters. The SAR202 cluster belonging to the phylum Chloroflexi was the first
      microbial lineage discovered to specifically inhabit the aphotic realm, where
      they are abundant and globally distributed. The absence of SAR202 cultured
      representatives is a significant bottleneck towards understanding their metabolic
      capacities and role in the marine environment. In this work, we use a combination
      of metagenome-assembled genomes from deep-sea datasets and publicly available
      single-cell genomes to construct a genomic perspective of SAR202 phylogeny,
      metabolism and biogeography. Our results suggest that SAR202 cluster members are
      medium sized, free-living cells with a heterotrophic lifestyle, broadly divided
      into two distinct clades. We present the first evidence of vertical
      stratification of these microbes along the meso- and bathypelagic ocean layers.
      Remarkably, two distinct species of SAR202 cluster are highly abundant in nearly
      all deep bathypelagic metagenomic datasets available so far. SAR202 members
      metabolize multiple organosulfur compounds, many appear to be sulfite-oxidizers
      and are predicted to play a major role in sulfur turnover in the dark water
      column. This concomitantly suggests an unsuspected availability of these nutrient
      sources to allow for the high abundance of these microbes in the deep sea.

PMID- 29208948
TI  - A novel mutation in SLC1A3 causes episodic ataxia.
AB  - Episodic ataxias (EAs) are rare channelopathies characterized by recurrent ataxia
      and vertigo, having eight subtypes. Mutated genes were found in four of these
      eight subtypes (EA1, EA2, EA5, and EA6). To date, only four missense mutations in
      the Solute Carrier Family 1 Member 3 gene (SLC1A3) have been reported to cause
      EA6. SLC1A3 encodes excitatory amino-acid transporter 1, which is a trimeric
      transmembrane protein responsible for glutamate transport in the synaptic cleft.
      In this study, we found a novel missense mutation, c.383T>G (p.Met128Arg) in
      SLC1A3, in an EA patient by whole-exome sequencing. The modeled structural
      analysis suggested that p.Met128Arg may affect the hydrophobic transmembrane
      environment and protein function. Analysis of the pathogenicity of all mutations
      found in SLC1A3 to date using multiple prediction tools showed some advantage of
      using the Mendelian Clinically Applicable Pathogenicity (M-CAP) score. Various
      types of SLC1A3 variants, including nonsense mutations and indels, in the ExAC
      database suggest that the loss-of-function mechanism by SLC1A3 mutations is
      unlikely in EA6. The current mutation (p.Med128Arg) presumably has a gain-of
      function effect as described in a previous report.

PMID- 29208949
TI  - Cooperation and the evolution of hunter-gatherer storytelling.
AB  - Storytelling is a human universal. From gathering around the camp-fire telling
      tales of ancestors to watching the latest television box-set, humans are
      inveterate producers and consumers of stories. Despite its ubiquity, little
      attention has been given to understanding the function and evolution of
      storytelling. Here we explore the impact of storytelling on hunter-gatherer
      cooperative behaviour and the individual-level fitness benefits to being a
      skilled storyteller. Stories told by the Agta, a Filipino hunter-gatherer
      population, convey messages relevant to coordinating behaviour in a foraging
      ecology, such as cooperation, sex equality and egalitarianism. These themes are
      present in narratives from other foraging societies. We also show that the
      presence of good storytellers is associated with increased cooperation. In
      return, skilled storytellers are preferred social partners and have greater
      reproductive success, providing a pathway by which group-beneficial behaviours,
      such as storytelling, can evolve via individual-level selection. We conclude that
      one of the adaptive functions of storytelling among hunter gatherers may be to
      organise cooperation.

PMID- 29208950
TI  - X-ray diffraction reveals the intrinsic difference in the physical properties of
      membrane and soluble proteins.
AB  - Membrane proteins are distinguished from soluble proteins by their insertion into
      biological membranes. This insertion is achieved via a noticeable arrangement of
      hydrophobic amino acids that are exposed at the surface of the protein, and
      renders the interaction with the aliphatic tails of lipids more energetically
      favorable. This important difference between these two categories of proteins is
      the source of the need for a specific handling of membrane proteins, which
      transpired in the creation of new tools for their recombinant expression,
      purification and even crystallization. Following this line, we show here that
      crystals of membrane proteins display systematically higher diffraction
      anisotropy than those of soluble proteins. This phenomenon dramatically hampers
      structure solution and refinement, and has a strong impact on the quality of
      electron-density maps. A farther search for origins of this phenomenon showed
      that the type of crystallization, and thus the crystal packing, has no impact on
      anisotropy, nor does the nature or function of the membrane protein. Membrane
      proteins fully embedded within the membrane display equal anisotropy compared to
      the ones with extra membranous domains or fusions with soluble proteins. Overall,
      these results overturn common beliefs and call for a specific handling of their
      diffraction data.

PMID- 29208951
TI  - Functional and spatial segregation within the inferior frontal and superior
      temporal cortices during listening, articulation imagery, and production of
      vowels.
AB  - Classical models of language localize speech perception in the left superior
      temporal and production in the inferior frontal cortex. Nonetheless,
      neuropsychological, structural and functional studies have questioned such
      subdivision, suggesting an interwoven organization of the speech function within
      these cortices. We tested whether sub-regions within frontal and temporal speech
      related areas retain specific phonological representations during both perception
      and production. Using functional magnetic resonance imaging and multivoxel
      pattern analysis, we showed functional and spatial segregation across the left
      fronto-temporal cortex during listening, imagery and production of vowels. In
      accordance with classical models of language and evidence from functional
      studies, the inferior frontal and superior temporal cortices discriminated among
      perceived and produced vowels respectively, also engaging in the non-classical,
      alternative function - i.e. perception in the inferior frontal and production in
      the superior temporal cortex. Crucially, though, contiguous and non-overlapping
      sub-regions within these hubs performed either the classical or non-classical
      function, the latter also representing non-linguistic sounds (i.e., pure tones).
      Extending previous results and in line with integration theories, our findings
      not only demonstrate that sensitivity to speech listening exists in production
      related regions and vice versa, but they also suggest that the nature of such
      interwoven organisation is built upon low-level perception.

PMID- 29208952
TI  - Major depletion of SOX2+ stem cells in the adult pituitary is not restored which
      does not affect hormonal cell homeostasis and remodelling.
AB  - The pituitary gland contains SOX2-expressing stem cells. However, their
      functional significance remains largely unmapped. We investigated their
      importance by depleting SOX2+ cells through diphtheria toxin (DT)-mediated
      ablation. DT treatment of adult Sox2CreERT2/+;R26iDTR/+ mice (after tamoxifen
      induced expression of DT receptor in SOX2+ cells) resulted in 80% obliteration of
      SOX2+ cells in the endocrine pituitary, coinciding with reduced pituisphere
      forming activity. Counterintuitively for a stem cell population, the SOX2+ cell
      compartment did not repopulate. Considering the more active phenotype of the stem
      cells during early-postnatal pituitary maturation, SOX2+ cell ablation was also
      performed in 4- and 1-week-old animals. Ablation grade diminished with decreasing
      age and was accompanied by a proliferative reaction of the SOX2+ cells,
      suggesting a rescue attempt. Despite this activation, SOX2+ cells did also not
      recover. Finally, the major SOX2+ cell depletion in adult mice did not affect the
      homeostatic maintenance of pituitary hormonal cell populations, nor the
      corticotrope remodelling response to adrenalectomy challenge. Taken together, our
      study shows that pituitary SOX2+ fail to regenerate after major depletion which
      does not affect adult endocrine cell homeostasis and remodelling. Thus, pituitary
      SOX2+ cells may constitute a copious stem cell reserve or may have other critical
      role(s) still to be clearly defined.

PMID- 29208953
TI  - Reconstructing ice-margin retreat using delta morphostratigraphy.
AB  - The paleogeographic reconstruction of the successive inland positions of a
      retreating ice sheet is generally constrained by mapping moraines. However,
      deltaic complexes constructed by sediment-charged meltwater can also provide a
      record of the retreating ice-margin positions. Here, we examine a serie of ice
      contact, ice-distal glaciofluvial and paraglacial depositional systems that
      developed along the Quebec North Shore (eastern Canada) in the context of falling
      relative sea level during the northward retreat of the Laurentide Ice Sheet
      (LIS). Ice-contact depositional systems formed when the LIS was stillstanding
      along the Quebec North Shore. Subsequent inland retreat of the ice margin
      generated glacial meltwaters feeding sediment to glaciofluvial deltas, leading to
      their rapid progradation. The retreat of the ice margin from drainage basins was
      marked by the onset of paraglacial processes such as the shutdown of delta
      progradation, severe fluvial entrenchment, and deposition of shallow-marine
      strata. Four end-member scenarios describe the spatial and stratigraphic
      distribution of these three depositional systems (ice-contact deposits, ice
      distal glaciofluvial deltas, and paraglacial suites). They reflect both the
      inherited drainage basin physiography and the retreat pattern of the ice margin.
      Applied to twenty deltaic complexes, these end-members allowed us to refine the
      model of LIS-margin retreat over southeastern Quebec.

PMID- 29208954
TI  - Monitoring trifluridine incorporation in the peripheral blood mononuclear cells
      of colorectal cancer patients under trifluridine/tipiracil medication.
AB  - Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer
      drug with efficacy validated for patients with metastatic colorectal cancer
      (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates
      the anticancer effect via its incorporation into DNA. However, it has not been
      examined whether FTD is incorporated into the tissues of patients who received
      TFTD medication. By detecting FTD incorporation into DNA by a specific antibody,
      we successfully detected FTD in the bone marrow and spleen cells isolated from
      FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs)
      activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also
      detected in PBMCs isolated from mCRC patients who had administrated TFTD
      medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed
      the percentage of FTD-positive PBMCs increased and decreased in parallel with the
      administration and cessation of TFTD medication, respectively. To our knowledge,
      this is the first report to detect an active cytotoxic component of a
      chemotherapeutic drug in clinical specimens using a specific antibody. This
      technique may enable us to predict the clinical benefits or the adverse effects
      of TFTD in mCRC patients.

PMID- 29208955
TI  - The interdomain flexible linker of the polypeptide GalNAc transferases dictates
      their long-range glycosylation preferences.
AB  - The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O
      glycosylation, consist of a catalytic and a lectin domain connected by a flexible
      linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit
      unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr)
      preferences modulated by the lectin domain. Here we report studies on GalNAc-T4
      that reveal the origins of its unique N-terminal long-range glycopeptide
      specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to
      a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is
      rotated relative to the homologous GalNAc-T2 structure, explaining their
      different long-range preferences. Kinetics and molecular dynamics simulations on
      several GalNAc-T2 flexible linker constructs show altered remote prior
      glycosylation preferences, confirming that the flexible linker dictates the
      rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range
      preferences. This work for the first time provides the structural basis for the
      different remote prior glycosylation preferences of the GalNAc-Ts.

PMID- 29208956
TI  - Poleta O-GlcNAcylation governs genome integrity during translesion DNA synthesis.
AB  - DNA polymerase eta (Poleta) facilitates translesion DNA synthesis (TLS) across
      ultraviolet (UV) irradiation- and cisplatin-induced DNA lesions implicated in
      skin carcinogenesis and chemoresistant phenotype formation, respectively.
      However, whether post-translational modifications of Poleta are involved in these
      processes remains largely unknown. Here, we reported that human Poleta undergoes
      O-GlcNAcylation at threonine 457 by O-GlcNAc transferase upon DNA damage.
      Abrogation of this modification results in a reduced level of CRL4CDT2-dependent
      Poleta polyubiquitination at lysine 462, a delayed p97-dependent removal of
      Poleta from replication forks, and significantly enhanced UV-induced mutagenesis
      even though Poleta focus formation and its efficacy to bypass across cyclobutane
      pyrimidine dimers after UV irradiation are not affected. Furthermore, the O
      GlcNAc-deficient T457A mutation impairs TLS to bypass across cisplatin-induced
      lesions, causing increased cellular sensitivity to cisplatin. Our findings
      demonstrate a novel role of Poleta O-GlcNAcylation in TLS regulation and genome
      stability maintenance and establish a new rationale to improve chemotherapeutic
      treatment.

PMID- 29208958
TI  - The positivity of estrogen receptor and progesterone receptor may not be
      associated with metastasis and recurrence in epithelial ovarian cancer.
AB  - The estrogen (ER) or progesterone receptors (PR) is positively associated with
      better clinical outcomes in ovarian cancer. Whether metastasis or recurrence of
      ovarian cancer is correlated with this association has not been investigated.
      Data on 894 women with epithelial ovarian cancer were collected and the
      association between ER or PR positivity and peritoneal or lymph node metastases
      or recurrence was analysed. ER or PR positivity was higher in high-grade, low
      grade serous and endometrioid carcinoma, but lower in mucinous and clear-cell
      carcinoma. Significantly higher ER or PR positivity was seen in endometrioid
      carcinoma or high-grade serous carcinoma with peritoneal metastases,
      respectively, but not other subtypes. In addition, there was no significant
      difference in ER or PR positivity between cases with and without lymph node
      metastasis in these five subtypes. In recurrent high-grade serous carcinoma with
      peritoneal metastases (n = 103), the positivity of ER or PR was 86% and 55%
      respectively. Our data demonstrate that the association between ER or PR
      positivity and peritoneal metastases was only seen in endometrioid or high grade
      serous carcinoma, respectively. There was no association of ER or PR positivity
      and lymph node metastases. The majority of recurrent high-grade serous carcinoma
      with peritoneal metastases (86%) were ER positive.

PMID- 29208959
TI  - Design and Synthesis of an Artificial Perpendicular Hard Ferrimagnet with High
      Thermal and Magnetic Field Stabilities.
AB  - It is of great fundamental and practical interest to develop effective means of
      modulating the magnetic hystereses of magnetic materials and their
      heterostructures. A notable example is the exchange bias (EB) effect between an
      antiferromagnet or ferrimagnet and a ferromagnet, which has been widely employed
      to manipulate magnetic anisotropy in spintronic devices and artificial magnets.
      Here, we report the design, synthesis and characterization of a synthetic
      perpendicularly-magnetized ferrimagnet based on [Mn2.9Ga/Co2MnSi]n superlattices,
      which attains thermal stability above 400 K and a coercive field up to 45 kOe
      through a mechanism of magnetic compensation. The structure is incorporated into
      a prototype Heusler alloy and MgO barrier based magnetic tunnel junction, which
      demonstrates high dynamic range linear field responses and an unusual in-plane EB
      effect. With increasing temperature, the coercive field reaches beyond 70 kOe at
      400 K in this device due to the increasing degree of magnetic moment compensation
      in the superlattice. The results demonstrate that the compensation mechanism can
      be utilized to achieve simultaneous thermal robustness and high coercivity in
      realistic spintronic devices.

PMID- 29208957
TI  - Neuronal signals regulate obesity induced beta-cell proliferation by FoxM1
      dependent mechanism.
AB  - Under insulin-resistant conditions such as obesity, pancreatic beta-cells
      proliferate to prevent blood glucose elevations. A liver-brain-pancreas neuronal
      relay plays an important role in this process. Here, we show the molecular
      mechanism underlying this compensatory beta-cell proliferation. We identify FoxM1
      activation in islets from neuronal relay-stimulated mice. Blockade of this relay,
      including vagotomy, inhibits obesity-induced activation of the beta-cell FoxM1
      pathway and suppresses beta-cell expansion. Inducible beta-cell-specific FoxM1
      deficiency also blocks compensatory beta-cell proliferation. In isolated islets,
      carbachol and PACAP/VIP synergistically promote beta-cell proliferation through a
      FoxM1-dependent mechanism. These findings indicate that vagal nerves that release
      several neurotransmitters may allow simultaneous activation of multiple pathways
      in beta-cells selectively, thereby efficiently promoting beta-cell proliferation
      and maintaining glucose homeostasis during obesity development. This neuronal
      signal-mediated mechanism holds potential for developing novel approaches to
      regenerating pancreatic beta-cells.

PMID- 29208960
TI  - MIF -173 G > C (rs755622) Gene Polymorphism Modulates Tuberculosis Risk: Evidence
      from a Meta-analysis and Trial Sequential Analysis.
AB  - The macrophage migration inhibitory factor (MIF) is a cytokine that plays an
      important role in inhibiting the growth of pathogenic Mycobacterium tuberculosis
      (M.tb) and regulates immune responses against M.tb pathogen. MIF -173 G > C gene
      polymorphism may affect immunity in an individual and leads to susceptibility to
      tuberculosis (TB). A large number of studies have investigated the relevance of
      this polymorphism with TB risk, but their results were inconclusive. To obtain a
      precise conclusion, a meta-analysis was performed by retrieving six eligible
      studies from Google Scholar, PubMed (Medline), and EMBASE online databases.
      Overall combined analysis suggested increased TB risk between MIF -173 G > C
      polymorphism and overall risk in four genetic models, i.e., allelic (C vs. G: p =
      0.001; OR = 1.517, 95% CI = 1.312 to 1.753), homozygous (CC vs. GG: p = 0.026; OR
      = 1.874, 95% CI = 1.079 to 3.257), heterozygous (GC vs. GG: p = 0.001; OR =
      1.542, 95% CI = 1.273 to 1.868) and dominant model (CC + GC vs. GG: p = 0.001; OR
      = 1.631, 95% CI = 1.362 to 1.955). Similarly, increased TB risk was observed in
      subgroup analysis of Asian ethnicity. No publication bias was observed. These
      results suggested that MIF -173 G > C variant is a significant risk factor for TB
      in overall and in Asian populations, and can be used as prognostic marker for TB
      susceptibility.

PMID- 29208961
TI  - Investigation of different nitrogen reduction routes and their key microbial
      players in wood chip-driven denitrification beds.
AB  - Field denitrification beds containing polymeric plant material are increasingly
      used to eliminate nitrate from agricultural drainage water. They mirror a number
      of anoxic ecosystems. However, knowledge of the microbial composition, the
      interaction of microbial species, and the carbon degradation processes within
      these denitrification systems is sparse. This study revealed several new aspects
      of the carbon and nitrogen cycle, and these findings can be correlated with the
      dynamics of the microbial community composition and the activity of key species.
      Members of the order Pseudomonadales seem to be important players in
      denitrification at low nitrate concentrations, while a switch to higher nitrate
      concentrations seems to select for members of the orders Rhodocyclales and
      Rhizobiales. We observed that high nitrate loading rates lead to an unpredictable
      transition of the community's activity from denitrification to dissimilatory
      reduction of nitrate to ammonium (DNRA). This transition is mirrored by an
      increase in transcripts of the nitrite reductase gene nrfAH and the increase
      correlates with the activity of members of the order Ignavibacteriales.
      Denitrification reactors sustained the development of an archaeal community
      consisting of members of the Bathyarchaeota and methanogens belonging to the
      Euryarchaeota. Unexpectedly, the activity of the methanogens positively
      correlated with the nitrate loading rates.

PMID- 29208962
TI  - Exploration of pyrazine-embedded antiaromatic polycyclic hydrocarbons generated
      by solution and on-surface azomethine ylide homocoupling.
AB  - Nanographenes, namely polycyclic aromatic hydrocarbons (PAHs) with nanoscale
      dimensions (>1 nm), are atomically precise cutouts from graphene. They represent
      prime models to enhance the scope of chemical and physical properties of graphene
      through structural modulation and functionalization. Defined nitrogen doping in
      nanographenes is particularly attractive due to its potential for increasing the
      number of pi-electrons, with the possibility of introducing localized
      antiaromatic ring elements. Herein we present azomethine ylide homocoupling as a
      strategy to afford internally nitrogen-doped, non-planar PAH in solution and
      planar nanographene on surfaces, with central pyrazine rings. Localized
      antiaromaticity of the central ring is indicated by optical absorption
      spectroscopy in conjunction with theoretical calculations. Our strategy opens up
      methods for chemically tailoring graphene and nanographenes, modified by
      antiaromatic dopants.

PMID- 29208963
TI  - Enhanced CD25+Foxp3+ regulatory T cell development by amodiaquine through
      activation of nuclear receptor 4A.
AB  - CD4+ T cells play key roles in the regulation of immune responses against
      pathogenic infectious antigens via development into effector T helper and induced
      regulatory T (iTreg) cells. Particularly, CD4+CD25+Foxp3+ iTreg cells are crucial
      for maintaining immune homeostasis and controlling inflammatory diseases. Anti
      inflammatory drugs that enhance iTreg cell generation would be effective at
      preventing and treating inflammatory and autoimmune diseases. In this study, we
      examined whether anti-malarial and anti-arthritic amodiaquine (AQ) could affect
      iTreg cell development. Despite the anti-proliferative activity of AQ, AQ only
      moderately decreased iTreg cell proliferation but substantially increased IL-2
      production by iTreg cells. Furthermore, AQ dose-dependently increased iTreg cell
      development and significantly upregulated iTreg cell markers including CD25.
      Interestingly, CD25 expression was decreased at later stages of iTreg cell
      development but was sustained in the presence of AQ, which was independent of IL
      2 signaling pathway. AQ directly increased CD25 gene transcription by enhancing
      the DNA-binding and transcriptional activity of nuclear receptor 4 A. Most
      importantly, in vivo administration of AQ attenuated inflammatory colitis,
      resulted in the increased iTreg cells and decreased inflammatory cytokines. The
      ability of anti-malarial AQ to potentiate iTreg cell development makes it a
      promising drug for preventing and treating inflammatory and autoimmune diseases.

PMID- 29208964
TI  - Reduced anxiety is associated with the accumulation of six serotonin reuptake
      inhibitors in wastewater treatment effluent exposed goldfish Carassius auratus.
AB  - Pharmaceuticals and personal care products (PPCPs) have been found in wastewater
      treatment plant (WWTP) effluents and their recipient watersheds. To assess the
      potential of WWTP effluents to alter fish behaviour, we caged male goldfish
      (Carassius auratus) for 21-days at three sites along a contamination gradient
      downstream from a WWTP which discharges into Cootes Paradise Marsh, on the
      western tip of Lake Ontario. We also included a fourth caging site as an external
      reference site within Lake Ontario at the Jordan Harbour Conservation Area. We
      then measured concentrations of PPCPs and monoamine neurotransmitters in caged
      goldfish plasma, and conducted behavioural assays measuring activity, startle
      response, and feeding. We detected fifteen different PPCPs in goldfish plasma
      including six serotonin reuptake inhibitors (amitriptyline, citalopram,
      fluoxetine/norfluoxetine, sertraline, venlafaxine, and diphenhydramine). Plasma
      concentrations of serotonin were significantly greater in plasma of fish caged
      closer to the WWTP effluent outfall site. The fish caged near and downstream of
      the WWTP effluent were bolder, more exploratory, and more active overall than
      fish caged at the reference site. Taken together, our results suggest that fish
      downstream of WWTPs are accumulating PPCPs at levels sufficient to alter
      neurotransmitter concentrations and to also impair ecologically-relevant
      behaviours.

PMID- 29208965
TI  - Network effects on coordination in asymmetric games.
AB  - Network structure can have an important effect on the behavior of players in an
      iterated 2 * 2 game. We study the effect of network structure on global and local
      behavior in asymmetric coordination games using best response dynamics. We find
      that global behavior is highly dependent on network topology. Random (Erdos
      Renyi) networks mostly converge to homogeneous behavior, but the higher the
      clustering in the network the more heterogeneous the behavior becomes. Behavior
      within the communities of the network is almost exclusively homogeneous. The
      findings suggest that clustering of networks facilitates self-organization of
      uniform behavior within clusters, but heterogeneous behavior between clusters. At
      the local level we find that some nodes are more important in determining the
      equilibrium behavior than other nodes. Degree centrality is for most networks the
      main predictor for the behavior and nodes with an even degree have an advantage
      over nodes with an uneven degree in dictating the behavior. We conclude that the
      behavior is difficult to predict for (Erdos-Renyi) networks and that the network
      imposes the behavior as a function of clustering and degree heterogeneity in
      other networks.

PMID- 29208966
TI  - A two-dimensional Fe-doped SnS2 magnetic semiconductor.
AB  - Magnetic two-dimensional materials have attracted considerable attention for
      their significant potential application in spintronics. In this study, we present
      a high-quality Fe-doped SnS2 monolayer exfoliated using a micromechanical
      cleavage method. Fe atoms were doped at the Sn atom sites, and the Fe contents
      are ~2.1%, 1.5%, and 1.1%. The field-effect transistors based on the
      Fe0.021Sn0.979S2 monolayer show n-type behavior and exhibit high optoelectronic
      performance. Magnetic measurements show that pure SnS2 is diamagnetic, whereas
      Fe0.021Sn0.979S2 exhibits ferromagnetic behavior with a perpendicular anisotropy
      at 2 K and a Curie temperature of ~31 K. Density functional theory calculations
      show that long-range ferromagnetic ordering in the Fe-doped SnS2 monolayer is
      energetically stable, and the estimated Curie temperature agrees well with the
      results of our experiment. The results suggest that Fe-doped SnS2 has significant
      potential in future nanoelectronic, magnetic, and optoelectronic applications.

PMID- 29208967
TI  - A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic
      target for intervertebral disc degeneration and associated pain.
AB  - Intervertebral disc (IVD) degeneration is a major cause of low back pain. The
      transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of
      inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to
      the pathogenesis IVD degeneration. We investigated the effects of inhibition of c
      Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224,
      significantly suppressed the interleukin-1beta-induced up-regulation of Mmp-3,
      Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse
      explant culture model of IVD degeneration. We used a tail disc percutaneous
      needle puncture method to further assess the effects of oral administration of T
      5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging
      (MRI) findings, and histology revealed that IVD degeneration was significantly
      mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as
      indicated by the extended tail-flick latency in response to heat stimulation of
      rats with needle-puncture-induced IVD degeneration. These findings suggest that
      the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain
      and that T-5224 may serve as a drug for the prevention of IVD degeneration.

PMID- 29208968
TI  - Simultaneous representation of a spectrum of dynamically changing value estimates
      during decision making.
AB  - Decisions are based on value expectations derived from experience. We show that
      dorsal anterior cingulate cortex and three other brain regions hold multiple
      representations of choice value based on different timescales of experience
      organized in terms of systematic gradients across the cortex. Some parts of each
      area represent value estimates based on recent reward experience while others
      represent value estimates based on experience over the longer term. The value
      estimates within these areas interact with one another according to their
      temporal scaling. Some aspects of the representations change dynamically as the
      environment changes. The spectrum of value estimates may act as a flexible
      selection mechanism for combining experience-derived value information with other
      aspects of value to allow flexible and adaptive decisions in changing
      environments.

PMID- 29208970
TI  - Integrated mRNA and microRNA transcriptome analysis reveals miRNA regulation in
      response to PVA in potato.
AB  - Potato (Solanum tuberosum L.) is the fourth most important crop worldwide. Potato
      virus A (PVA) is one of the most harmful viruses infecting potatoes. However, the
      molecular mechanisms governing the responses to PVA infection in potato at the
      transcriptional and post-transcriptional levels are not well understood. In this
      study, we performed both mRNA and small RNA sequencing in potato leaves to
      identify the genes and miRNAs involved in the response to PVA infection. A total
      of 2,062 differentially expressed genes (DEGs) and 201 miRNAs (DEMs) were
      identified, respectively. Gene ontology (GO) and KEGG analysis revealed that
      these DEGs were involved in the transduction of pathogen signals, transcriptional
      reprogramming, induction of hormone signaling, activation of pathogenesis-related
      (PR) genes, and changes in secondary metabolism. Small RNA sequencing revealed 58
      miRNA-mRNA interactions related to PVA infection. Some of the miRNAs (stu-miR482d
      3p, stu-miR397-5p, etc) which target PR genes showed negative correlations
      between the DEMs and DEGs. Eight of the DEGs and three DEMs with their target
      genes were further validated by quantitative real time-PCR (qRT-PCR). Overall,
      this study provides a transcriptome-wide insight into the molecular basis of
      resistance to PVA infection in potato leaves and potenital candidate genes for
      improving resistance cultivars.

PMID- 29208969
TI  - Association of kidney fibrosis with urinary peptides: a path towards non-invasive
      liquid biopsies?
AB  - Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality
      worldwide. A hallmark of CKD progression is renal fibrosis characterized by
      excessive accumulation of extracellular matrix (ECM) proteins. In this study, we
      aimed to investigate the correlation of the urinary proteome classifier CKD273
      and individual urinary peptides with the degree of fibrosis. In total, 42 kidney
      biopsies and urine samples were examined. The percentage of fibrosis per total
      tissue area was assessed in Masson trichrome stained kidney tissues. The urinary
      proteome was analysed by capillary electrophoresis coupled to mass spectrometry.
      CKD273 displayed a significant and positive correlation with the degree of
      fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters
      (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein
      to-creatinine ratio) did not (Rho = -0.222; -0.137; -0.070 and P = 0.16; 0.39;
      0.66, respectively). We identified seven fibrosis-associated peptides displaying
      a significant and negative correlation with the degree of fibrosis. All peptides
      were collagen fragments, suggesting that these may be causally related to the
      observed accumulation of ECM in the kidneys. CKD273 and specific peptides are
      significantly associated with kidney fibrosis; such an association could not be
      detected by other biomarkers for CKD. These non-invasive fibrosis-related
      biomarkers can potentially be implemented in future trials.

PMID- 29208971
TI  - Association between nonspecific interstitial pneumonia and presence of CD20+ B
      lymphocytes within pulmonary lymphoid follicles.
AB  - Nonspecific interstitial pneumonia (NSIP) is characterised by interstitial
      infiltration of lymphocytes and varying amounts of interstitial fibrosis. B cells
      have been suggested to contribute to the pathogenesis of NSIP. However, the
      relationship between B-lymphocyte and the clinical outcomes of NSIP was unclear.
      In this study, 50 patients with histopathologically confirmed NSIP from Peking
      Union Medical College Hospital between April 2003 to December 2012 were
      retrospectively analyzed. Using immunohistochemical analyses, CD20+ B cells were
      counted in the lymphoid follicles, perivascular, interstitial, and
      peribronchiolar regions of lung tissure. The CD20+ lymphocytes were mainly
      present in the lymphoid follicles. The number of follicular CD20+ lymphocytes was
      higher in the fibrosing than cellular NSIP pattern [255.08 (132.92-449.71) vs.
      121.33 (63.54-282.88)/0.1 mm2, p = 0.017]. After 1 year of therapy, the
      follicular CD20+ lymphocytes were significantly higher in patients whose forced
      vital capacity (FVC) worsened as compared to those who improved (p = 0.014).
      Additionally, follicular CD20+ lymphocytes were negatively correlated with the
      post-treatment percentage change in FVC (rho = -0.397, p = 0.004). However,
      follicular CD20+ lymphocytes were not correlated with survival. These results
      suggested that pulmonary follicular CD20+ lymphocytes were correlated with the
      fibrosing pattern of NSIP and predicted less clinical improvement after
      treatment.

PMID- 29208972
TI  - Effects of 1,25 and 24,25 Vitamin D on Corneal Epithelial Proliferation,
      Migration and Vitamin D Metabolizing and Catabolizing Enzymes.
AB  - This study investigated the effects of 1,25(OH)2D3 and 24R,25(OH)2D3 on corneal
      epithelial cell proliferation, migration, and on the vitamin D activating enzyme
      CYP27B1 (produces 1,25(OH)2D3) and inactivating enzyme CYP24A1 (produces
      24R,25(OH)2D3). The role of the vitamin D receptor (VDR) was also examined. In
      VDR wildtype mouse corneal epithelial cells (WT), 1,25(OH)2D3 increased CYP24A1
      protein expression and decreased CYP27B1 expression. In VDR knockout mouse
      epithelial cells (KO), 1,25(OH)2D3 increased CYP24A1 and CYP27B1 protein
      expression. 1,25(OH)2D3 did not affect WT cell proliferation, but did stimulate
      VDR KO cell proliferation. In a human corneal epithelial cell line (HCEC),
      1,25(OH)2D3 increased CYP24A1 mRNA and protein expression. 1,25(OH)2D3 increased
      CYP27B1 mRNA levels in HCEC, but had no effect on CYP27B1 protein levels.
      1,25(OH)2D3 inhibited HCEC proliferation and stimulated cell migration in primary
      human epithelial cells. 24,25(OH)2D3, on the other hand, increased both CYP24A1
      and CYP27B1 protein expression in WT and VDR KO cells, and stimulated cell
      proliferation in both WT and KO cells. In HCEC, 24,25(OH)2D3 increased CYP24A1
      and CYP27B1 mRNA and protein expression, and stimulated cell migration. In human
      primary corneal epithelial cells, 24,25(OH)2D3 stimulated migration. We conclude
      that 24R,25(OH)2D3 is likely involved in corneal epithelial cell regulation
      independent of 1,25(OH)2D3 or VDR.

PMID- 29208973
TI  - Coupling of sea level and tidal range changes, with implications for future water
      levels.
AB  - Are perturbations to ocean tides correlated with changing sea-level and climate,
      and how will this affect high water levels? Here, we survey 152 tide gauges in
      the Pacific Ocean and South China Sea and statistically evaluate how the sum of
      the four largest tidal constituents, a proxy for the highest astronomical tide
      (HAT), changes over seasonal and interannual time scales. We find that the
      variability in HAT is significantly correlated with sea-level variability;
      approximately 35% of stations exhibit a greater than +/-50 mm tidal change per
      meter sea-level fluctuation. Focusing on a subset of three stations with long
      records, probability density function (PDF) analyses of the 95% percentile
      exceedance of total sea level (TSL) show long-term changes of this high-water
      metric. At Hong Kong, the increase in tides significantly amplifies the risk
      caused by sea-level rise. Regions of tidal decrease and/or amplification
      highlight the non-linear response to sea-level variations, with the potential to
      amplify or mitigate against the increased flood risk caused by sea-level rise.
      Overall, our analysis suggests that in many regions, local flood level
      determinations should consider the joint effects of non-stationary tides and mean
      sea level (MSL) at multiple time scales.

PMID- 29208974
TI  - Bioaccumulation of pharmaceuticals and personal care product chemicals in fish
      exposed to wastewater effluent in an urban wetland.
AB  - The bioaccumulation of a broad range of pharmaceuticals and personal care product
      chemicals (PPCPs) was studied in Cootes Paradise Marsh (CPM), an urban wetland
      that receives tertiary treated municipal waste waters as well as urban storm
      runoff. We measured PPCPs in caged and wild goldfish, as well as wild carp, and
      compared observed bioaccumulation factors (BAFP) using concentrations in surface
      waters and fish blood plasma, with modeled BAFs. Thirty-two PPCPs were detected
      in water from the central CPM site (CPM3) while 64 PPCPs were found at higher
      concentrations at a site immediately downstream of the effluent outflow (CPM1).
      Following a 3-week deployment, 15 PPCPs were detected in the plasma of caged
      goldfish at CPM1, and 14 at CPM3, compared to only 3 in goldfish caged at a
      reference site. The highest BAFP in goldfish were for the antidepressant
      Sigmafluoxetine averaging 386 L/kg in caged and 906 L/kg in wild goldfish,
      respectively. In carp, SigmaDiazepam (diazepam and oxazepam) had the highest BAFP
      (927 L/kg). This study identified a broader range of PPCPs in fish and surface
      waters than previously reported. However, modeled BAFs did not show good
      agreement with observed whole body or plasma BAFs, demonstrating that more work
      is needed to better explain bioaccumulation of PPCPs.

PMID- 29208975
TI  - A numerical treatment of radiative nanofluid 3D flow containing gyrotactic
      microorganism with anisotropic slip, binary chemical reaction and activation
      energy.
AB  - A numerical investigation of steady three dimensional nanofluid flow carrying
      effects of gyrotactic microorganism with anisotropic slip condition along a
      moving plate near a stagnation point is conducted. Additionally, influences of
      Arrhenius activation energy, joule heating accompanying binary chemical reaction
      and viscous dissipation are also taken into account. A system of nonlinear
      differential equations obtained from boundary layer partial differential
      equations is found by utilization of apposite transformations. RK fourth and
      fifth order technique of Maple software is engaged to acquire the solution of the
      mathematical model governing the presented fluid flow. A Comparison with
      previously done study is also made and a good agreement is achieved with existing
      results; hence reliable results are being presented. Evaluations are carried out
      for involved parameters graphically against velocity, temperature, concentration
      fields, microorganism distribution, density number, local Nusselt and Sherwood
      numbers. It is detected that microorganism distribution exhibit diminishing
      behavior for rising values of bio-convection Lewis and Peclet numbers.

PMID- 29208976
TI  - Dynamical system with plastic self-organized velocity field as an alternative
      conceptual model of a cognitive system.
AB  - It is well known that architecturally the brain is a neural network, i.e. a
      collection of many relatively simple units coupled flexibly. However, it has been
      unclear how the possession of this architecture enables higher-level cognitive
      functions, which are unique to the brain. Here, we consider the brain from the
      viewpoint of dynamical systems theory and hypothesize that the unique feature of
      the brain, the self-organized plasticity of its architecture, could represent the
      means of enabling the self-organized plasticity of its velocity vector field. We
      propose that, conceptually, the principle of cognition could amount to the
      existence of appropriate rules governing self-organization of the velocity field
      of a dynamical system with an appropriate account of stimuli. To support this
      hypothesis, we propose a simple non-neuromorphic mathematical model with a
      plastic self-organized velocity field, which has no prototype in physical world.
      This system is shown to be capable of basic cognition, which is illustrated
      numerically and with musical data. Our conceptual model could provide an
      additional insight into the working principles of the brain. Moreover, hardware
      implementations of plastic velocity fields self-organizing according to various
      rules could pave the way to creating artificial intelligence of a novel type.

PMID- 29208978
TI  - Algae associated with coral degradation affects risk assessment in coral reef
      fishes.
AB  - Habitat degradation alters the chemical landscape through which information about
      community dynamics is transmitted. Olfactory information is crucial for risk
      assessment in aquatic organisms as predators release odours when they capture
      prey that lead to an alarm response in conspecific prey. Recent studies show some
      coral reef fishes are unable to use alarm odours when surrounded by dead-degraded
      coral. Our study examines the spatial and temporal dynamics of this alarm odour
      nullifying effect, and which substratum types may be responsible. Field
      experiments showed that settlement-stage damselfish were not able to detect alarm
      odours within 2 m downcurrent of degraded coral, and that the antipredator
      response was re-established 20-40 min after transferral to live coral. Laboratory
      experiments indicate that the chemicals from common components of the degraded
      habitats, the cyanobacteria, Okeania sp., and diatom, Pseudo-nitzschia
      sp.prevented an alarm odour response. The same nullifying effect was found for
      the common red algae, Galaxauria robusta, suggesting that the problem is of a
      broader nature than previously realised. Those fish species best able to
      compensate for a lack of olfactory risk information at key times will be those
      potentially most resilient to the effects of coral degradation that operate
      through this mechanism.

PMID- 29208977
TI  - Protein Structure Insights into the Bilayer Interactions of the Saposin-Like
      Domain of Solanum tuberosum Aspartic Protease.
AB  - Many plant aspartic proteases contain a saposin-like domain whose principal
      functions are intracellular sorting and host defence. Its structure is
      characterised by helical segments cross-linked by three highly conserved
      cystines. The present study on the saposin-like domain of Solanum tuberosum
      aspartic protease revealed that acidification from inactive to active conditions
      causes dimerisation and a strand-to-helix secondary structure transition
      independent of bilayer interaction. Bilayer fusion was shown to occur under
      reducing conditions yielding a faster shift to larger vesicle sizes relative to
      native conditions, implying that a lower level structural motif might be bilayer
      active. Characterisation of peptide sequences based on the domain's secondary
      structural regions showed helix-3 to be active (~4% of the full domain's
      activity), and mutation of its sole positively charged residue resulted in loss
      of activity and disordering of structure. Also, the peptides' respective circular
      dichroism spectra suggested that native folding within the full domain is
      dependent on surrounding structure. Overall, the present study reveals that the
      aspartic protease saposin-like domain active structure is an open saposin fold
      dimer whose formation is pH-dependent, and that a bilayer-active motif shared
      among non-saposin membrane-active proteins including certain plant defence
      proteins is nested within an overall structure essential for native
      functionality.

PMID- 29208979
TI  - Induction of antimicrobial peptides secretion by IL-1beta enhances human amniotic
      membrane for regenerative medicine.
AB  - Due to antibacterial characteristic, amnion has been frequently used in different
      clinical situations. Developing an in vitro method to augment endogenous
      antibacterial ingredient of amniotic epithelial and mesenchymal stem cells is
      desirable for a higher efficacy of this promising biomaterial. In this study,
      epithelial or mesenchymal side dependent effect of amniotic membrane (AM) on
      antibacterial activity against some laboratory and clinical isolated strains was
      investigated by modified disk diffusion method and colony count assay. The effect
      of exposure to IL-1beta in production and release of antibacterial ingredients
      was investigated by ELISA assay. The results showed that there is no significant
      difference between epithelial and mesenchymal sides of amnion in inhibition of
      bacterial growth. Although the results of disk diffusion showed that the AM
      inhibitory effect depends on bacterial genus and strain, colony count assay
      showed that the extract of AM inhibits all investigated bacterial strains. The
      exposure of AM to IL-1beta leads to a higher level of antibacterial peptides
      secretion including elafin, HBD-2, HBD-3 and cathelicidic LL-37. Based on these
      results, amniotic cells possess antibacterial activity which can be augmented by
      inflammatory signal inducers; a process which make amnion and its epithelial and
      mesenchymal stem cells more suitable for tissue engineering and regenerative
      medicine.

PMID- 29208981
TI  - Influence of Spatial and Chromatic Noise on Luminance Discrimination.
AB  - Pseudoisochromatic figures are designed to base discrimination of a chromatic
      target from a background solely on the chromatic differences. This is
      accomplished by the introduction of luminance and spatial noise thereby
      eliminating these two dimensions as cues. The inverse rationale could also be
      applied to luminance discrimination, if spatial and chromatic noise are used to
      mask those cues. In this current study estimate of luminance contrast thresholds
      were conducted using a novel stimulus, based on the use of chromatic and spatial
      noise to mask the use of these cues in a luminance discrimination task. This was
      accomplished by presenting stimuli composed of a mosaic of circles colored
      randomly. A Landolt-C target differed from the background only by the luminance.
      The luminance contrast thresholds were estimated for different chromatic noise
      saturation conditions and compared to luminance contrast thresholds estimated
      using the same target in a non-mosaic stimulus. Moreover, the influence of the
      chromatic content in the noise on the luminance contrast threshold was also
      investigated. Luminance contrast threshold was dependent on the chromaticity
      noise strength. It was 10-fold higher than thresholds estimated from non-mosaic
      stimulus, but they were independent of colour space location in which the noise
      was modulated. The present study introduces a new method to investigate luminance
      vision intended for both basic science and clinical applications.

PMID- 29208980
TI  - Long-term drug modification to the surface of mesenchymal stem cells by the
      avidin-biotin complex method.
AB  - Mesenchymal stem cells (MSCs) have various functions, making a significant
      contribution to tissue repair. On the other hand, the viability and function of
      MSCs are not lasting after an in vivo transplant, and the therapeutic effects of
      MSCs are limited. Although various chemical modification methods have been
      applied to MSCs to improve their viability and function, most of conventional
      drug modification methods are short-term and unstable and cause cytotoxicity. In
      this study, we developed a method for long-term drug modification to C3H10T1/2
      cells, murine mesenchymal stem cells, without any damage, using the avidin-biotin
      complex method (ABC method). The modification of NanoLuc luciferase (Nluc), a
      reporter protein, to C3H10T1/2 cells by the ABC method lasted for at least 14
      days in vitro without major effects on the cellular characteristics (cell
      viability, cell proliferation, migration ability, and differentiation ability).
      Moreover, in vivo, the surface Nluc modification to C3H10T1/2 cells by the ABC
      method lasted for at least 7 days. Therefore, these results indicate that the ABC
      method may be useful for long-term surface modification of drugs and for
      effective MSC-based therapy.

PMID- 29208982
TI  - Peretinoin, an acyclic retinoid, inhibits hepatocarcinogenesis by suppressing
      sphingosine kinase 1 expression in vitro and in vivo.
AB  - Sphingosine-1-phospate is a potent bioactive lipid metabolite that regulates
      cancer progression. Because sphingosine kinase 1 and sphingosine kinase 2 (SPHK
      1/2) are both essential for sphingosine-1-phospate production, they could be a
      therapeutic target in various cancers. Peretinoin, an acyclic retinoid, inhibits
      post-therapeutic recurrence of hepatocellular carcinoma via unclear mechanisms.
      In this study, we assessed effects of peretinoin on SPHK expression and liver
      cancer development in vitro and in vivo. We examined effects of peretinoin on
      expression, enzymatic and promoter activity of SPHK1 in a human hepatoma cell
      line, Huh-7. We also investigated effects of SPHK1 on hepatocarcinogenesis
      induced by diethylnitrosamine using SPHK1 knockout mice. Peretinoin treatment of
      Huh-7 cells reduced mRNA levels, protein expression and enzymatic activity of
      SPHK1. Peretinoin reduced SPHK1 promoter activity; this effect of peretinoin was
      blocked by overexpression of Sp1, a transcription factor. Deletion of all Sp1
      binding sites within the SPHK1 promoter region abolished SPHK1 promoter activity,
      suggesting that peretinoin reduced mRNA levels of SPHK1 via Sp1. Additionally,
      diethylnitrosamine-induced hepatoma was fewer and less frequent in SPHK1 knockout
      compared to wild-type mice. Our data showed crucial roles of SPHK1 in
      hepatocarcinogenesis and suggests that peretinoin prevents hepatocarcinogenesis
      by suppressing mRNA levels of SPHK1.

PMID- 29208983
TI  - Comprehensive statistical inference of the clonal structure of cancer from
      multiple biopsies.
AB  - A comprehensive characterization of tumor genetic heterogeneity is critical for
      understanding how cancers evolve and escape treatment. Although many algorithms
      have been developed for capturing tumor heterogeneity, they are designed for
      analyzing either a single type of genomic aberration or individual biopsies. Here
      we present THEMIS (Tumor Heterogeneity Extensible Modeling via an Integrative
      System), which allows for the joint analysis of different types of genomic
      aberrations from multiple biopsies taken from the same patient, using a dynamic
      graphical model. Simulation experiments demonstrate higher accuracy of THEMIS
      over its ancestor, TITAN. The heterogeneity analysis results from THEMIS are
      validated with single cell DNA sequencing from a clinical tumor biopsy. When
      THEMIS is used to analyze tumor heterogeneity among multiple biopsies from the
      same patient, it helps to reveal the mutation accumulation history, track cancer
      progression, and identify the mutations related to treatment resistance. We
      implement our model via an extensible modeling platform, which makes our approach
      open, reproducible, and easy for others to extend.

PMID- 29208984
TI  - A nonlinear approach to identify pathological change of thyroid nodules based on
      statistical analysis of ultrasound RF signals.
AB  - In order to reassure the majority of patients with benign nodules from
      unnecessary needle biopsy, there is an increasing clinical requirement to
      identify benign and malignant thyroid nodules during ultrasound diagnosis. A
      nonlinear approach based on statistical analysis of ultrasound radio-frequency
      (RF) signals was developed for differential diagnosing the thyroid nodules to
      improve the diagnostic accuracy. Data from 44 patients with solitary thyroid
      nodules were collected, following with the ultrasound-guided fine needle
      aspiration (FNA) as the ground truth. The relative P-value (rP-value) was
      estimated to quantify the pathophysiologic changes by comparing the region of
      interest (ROI) with the no pathological change part in the thyroid gland using
      only one frame of raw RF data. The malignant nodules were distinguished from
      benign ones with high accuracy and high credibility (sensitivity = 100%,
      specificity = 80%). Suspicious nodules (rP-value < 0.5) could be picked out for
      FNA with no additional instruments. This method shows promising in
      differentiating malignant from benign thyroid nodules, subsequently avoiding
      unnecessary biopsies.

PMID- 29208985
TI  - Impact of remotely generated eddies on plume dispersion at abyssal mining sites
      in the Pacific.
AB  - Proposed harvesting of polymetallic nodules in the Central Tropical Pacific will
      generate plumes of suspended sediment which are anticipated to be ecologically
      harmful. While the deep sea is low in energy, it also can be highly turbulent,
      since the vertical density gradient which suppresses turbulence is weak. The
      ability to predict the impact of deep plumes is limited by scarcity of in-situ
      observations. Our observations show that the low-energy environment more than
      four kilometres below the surface ultimately becomes an order of magnitude more
      energetic for periods of weeks in response to the passage of mesoscale eddies.
      The source of these eddies is remote in time and space, here identified as the
      Central American Gap Winds. Abyssal current variability is controlled by
      comparable contributions from tides, surface winds and passing eddies. During
      eddy-induced elevated flow periods mining-related plumes, potentially
      supplemented by natural sediment resuspension, are expected to spread and
      disperse more widely and rapidly. Predictions are given of the timing, location
      and scales of impact.

PMID- 29208986
TI  - Immune tuning scaffold for the local induction of a pro-regenerative environment.
AB  - In mammals, tissue regeneration is accomplished through a well-regulated, complex
      cascade of events. The disruption of the cellular and molecular processes
      involved in tissue healing might lead to scar formation. Most tissue engineering
      approaches have tried to improve the regenerative outcome following an injury,
      through the combination of biocompatible materials, stem cells and bioactive
      factors. However, implanted materials can cause further healing impairments due
      to the persistent inflammatory stimuli that trigger the onset of chronic
      inflammation. Here, it is described at the molecular, cellular and tissue level,
      the body response to a functionalized biomimetic collagen scaffold. The grafting
      of chondroitin sulfate on the surface of the scaffold is able to induce a pro
      regenerative environment at the site of a subcutaneous implant. The early in situ
      recruitment, and sustained local retention of anti-inflammatory macrophages
      significantly reduced the pro-inflammatory environment and triggered a different
      healing cascade, ultimately leading to collagen fibril re-organization, blood
      vessel formation, and scaffold integration with the surrounding native tissue.

PMID- 29208988
TI  - Similarity-based Regularized Latent Feature Model for Link Prediction in
      Bipartite Networks.
AB  - Link prediction is an attractive research topic in the field of data mining and
      has significant applications in improving performance of recommendation system
      and exploring evolving mechanisms of the complex networks. A variety of complex
      systems in real world should be abstractly represented as bipartite networks, in
      which there are two types of nodes and no links connect nodes of the same type.
      In this paper, we propose a framework for link prediction in bipartite networks
      by combining the similarity based structure and the latent feature model from a
      new perspective. The framework is called Similarity Regularized Nonnegative
      Matrix Factorization (SRNMF), which explicitly takes the local characteristics
      into consideration and encodes the geometrical information of the networks by
      constructing a similarity based matrix. We also develop an iterative scheme to
      solve the objective function based on gradient descent. Extensive experiments on
      a variety of real world bipartite networks show that the proposed framework of
      link prediction has a more competitive, preferable and stable performance in
      comparison with the state-of-art methods.

PMID- 29208987
TI  - Genome-wide DNA methylation changes associated with olfactory learning and memory
      in Apis mellifera.
AB  - The honeybee is a model organism for studying learning and memory formation and
      its underlying molecular mechanisms. While DNA methylation is well studied in
      caste differentiation, its role in learning and memory is not clear in honeybees.
      Here, we analyzed genome-wide DNA methylation changes during olfactory learning
      and memory process in A. mellifera using whole genome bisulfite sequencing (WGBS)
      method. A total of 853 significantly differentially methylated regions (DMRs) and
      963 differentially methylated genes (DMGs) were identified. We discovered that
      440 DMRs of 648 genes were hypermethylated and 274 DMRs of 336 genes were
      hypomethylated in trained group compared to untrained group. Of these DMGs, many
      are critical genes involved in learning and memory, such as Creb, GABA B R and
      Ip3k, indicating extensive involvement of DNA methylation in honeybee olfactory
      learning and memory process. Furthermore, key enzymes for histone methylation,
      RNA editing and miRNA processing also showed methylation changes during this
      process, implying that DNA methylation can affect learning and memory of
      honeybees by regulating other epigenetic modification processes.

PMID- 29208989
TI  - Germination Biology of Two Invasive Physalis Species and Implications for Their
      Management in Arid and Semi-arid Regions.
AB  - Two Solanaceae invasive plant species (Physalis angulata L. and P. philadelphica
      Lam. var. immaculata Waterfall) infest several arable crops and natural habitats
      in Southeastern Anatolia region, Turkey. However, almost no information is
      available regarding germination biology of both species. We performed several
      experiments to infer the effects of environmental factors on seed germination and
      seedling emergence of different populations of both species collected from
      various locations with different elevations and habitat characteristics. Seed
      dormancy level of all populations was decreased with increasing age of the seeds.
      Seed dormancy of freshly harvested and aged seeds of all populations was
      effectively released by running tap water. Germination was slightly affected by
      photoperiods, which suggests that seeds are slightly photoblastic. All seeds
      germinated under wide range of temperature (15-40  degrees C), pH (4-10), osmotic
      potential (0 to -1.2 MPa) and salinity (0-400 mM sodium chloride) levels. The
      germination ability of both plant species under wide range of environmental
      conditions suggests further invasion potential towards non-infested areas in the
      country. Increasing seed burial depth significantly reduced the seedling
      emergence, and seeds buried below 4 cm of soil surface were unable to emerge. In
      arable lands, soil inversion to maximum depth of emergence (i.e., 6 cm) followed
      by conservational tillage could be utilized as a viable management option.

PMID- 29208990
TI  - Comparative transcriptomic analysis of Tibetan Gynaephora to explore the genetic
      basis of insect adaptation to divergent altitude environments.
AB  - Adaptation of insects to different altitudes remain largely unknown, especially
      those endemic to the Tibetan Plateau (TP). Here, we generated the transcriptomes
      of Gynaephora menyuanensis and G. alpherakii, inhabiting different high altitudes
      on the TP, and used these and the previously available transcriptomic and genomic
      sequences from low-altitude insects to explore potential genetic basis for
      divergent high-altitude adaptation in Gynaephora. An analysis of 5,869
      orthologous genes among Gynaephora and other three low-altitude insects uncovered
      that fast-evolving genes and positively selected genes (PSGs) in the two
      Gynaephora species were enriched in energy metabolism and hypoxia response
      categories (e.g. mitochondrion, oxidation-reduction process, and response to
      oxidative stress). Particularly, mTOR signaling pathway involving hypoxia was
      enriched by PSGs, indicating this well-known pathway in mammal hypoxia adaptation
      may be an important signaling system in Gynaephora. Furthermore, some PSGs were
      associated with response to hypoxia (e.g. cytochrome proteins), cold (e.g.
      dehydrogenase) and DNA repair (e.g. DNA repair proteins). Interestingly, several
      insect-specific genes that were associated with exoskeleton and cuticle
      development (e.g. chitinase and ecdysteroids) had experienced positive selection,
      suggesting the specific adaptive mechanisms in insects. This study is favourable
      for understanding the adaptive evolution of Gynaephora and even TP insects to
      divergent altitudes.

PMID- 29208991
TI  - High-definition tDCS of the temporo-parietal cortex enhances access to newly
      learned words.
AB  - Learning associations between words and their referents is crucial for language
      learning in the developing and adult brain and for language re-learning after
      neurological injury. Non-invasive transcranial direct current stimulation (tDCS)
      to the posterior temporo-parietal cortex has been suggested to enhance this
      process. However, previous studies employed standard tDCS set-ups that induce
      diffuse current flow in the brain, preventing the attribution of stimulation
      effects to the target region. This study employed high-definition tDCS (HD-tDCS)
      that allowed the current flow to be constrained to the temporo-parietal cortex,
      to clarify its role in novel word learning. In a sham-controlled, double-blind,
      between-subjects design, 50 healthy adults learned associations between legal non
      words and unfamiliar object pictures. Participants were stratified by baseline
      learning ability on a short version of the learning paradigm and pairwise
      randomized to active (20 mins; N = 25) or sham (40 seconds; N = 25) HD-tDCS.
      Accuracy was comparable during the baseline and experimental phases in both HD
      tDCS conditions. However, active HD-tDCS resulted in faster retrieval of correct
      word-picture pairs. Our findings corroborate the critical role of the temporo
      parietal cortex in novel word learning, which has implications for current
      theories of language acquisition.

PMID- 29208992
TI  - Author Correction: Intermediate degrees of synergistic pleiotropy drive adaptive
      evolution in ecological time.
AB  - In the version of this Article previously published, there was a typographical
      error ('4' instead of '2') in the equations relating F ST and effective
      population size (N e) in the Methods section 'Genome-wide scan for selection
      based on temporal differentiation'. The correct equations are given
      below.[Formula: see text] [Formula: see text].

PMID- 29208993
TI  - Author Correction: The social and cultural roots of whale and dolphin brains.
AB  - In Table 1 of the Supplementary Information, the data presented in the column
      'Corrected social repertoire' were incorrect. This error does not affect the
      analyses, statistics or conclusions of the study, which employed the correct
      values. The data have now been corrected in the Supplementary file.

PMID- 29208994
TI  - Author Correction: The global distribution of tetrapods reveals a need for
      targeted reptile conservation.

PMID- 29208995
TI  - C-Phycocyanin protects against mitochondrial dysfunction and oxidative stress in
      parthenogenetic porcine embryos.
AB  - C-Phycocyanin (CP) is a biliprotein enriched in blue-green algae that is known to
      possess antioxidant, anti-apoptosis, anti-inflammatory, and radical-scavenging
      properties in somatic cells. However, the protective effect of CP on porcine
      embryo developmental competence in vitro remains unclear. In the present study,
      we investigated the effect of CP on the development of early porcine embryos as
      well as its underlying mechanisms. Different concentrations of CP (2, 5, 8, 10
      MUg/mL) were added to porcine zygote medium 5 during in vitro culture. The
      results showed that 5 MUg/mL CP significantly increased blastocyst formation and
      hatching rate. Blastocyst formation and quality were significantly increased in
      the 50 MUM H2O2 treatment group following 5 MUg/mL CP addition. CP prevented the
      H2O2-induced compromise of mitochondrial membrane potential, release of
      cytochrome c from the mitochondria, and reactive oxygen species generation.
      Furthermore, apoptosis, DNA damage level, and autophagy in the blastocysts were
      attenuated by supplementation of CP in the H2O2-induced oxidative injury group
      compared to in controls. These results suggest that CP has beneficial effects on
      the development of porcine parthenotes by attenuating mitochondrial dysfunction
      and oxidative stress.

PMID- 29208996
TI  - Relativistic inverse Compton scattering of photons from the early universe.
AB  - Electrons at relativistic speeds, diffusing in magnetic fields, cause copious
      emission at radio frequencies in both clusters of galaxies and radio galaxies
      through non-thermal radiation emission called synchrotron. However, the total
      power radiated through this mechanism is ill constrained, as the lower limit of
      the electron energy distribution, or low-energy cutoffs, for radio emission in
      galaxy clusters and radio galaxies, have not yet been determined. This lower
      limit, parametrized by the lower limit of the electron momentum - pmin - is
      critical for estimating the total energetics of non-thermal electrons produced by
      cluster mergers or injected by radio galaxy jets, which impacts the formation of
      large-scale structure in the universe, as well as the evolution of local
      structures inside galaxy clusters. The total pressure due to the relativistic,
      non-thermal population of electrons can be measured using the Sunyaev-Zel'dovich
      Effect, and is critically dependent on pmin, making the measurement of this non
      thermal pressure a promising technique to estimate the electron low-energy
      cutoff. We present here the first unambiguous detection of this Sunyaev
      Zel'dovich Effect for a non-thermal population of electrons in a radio galaxy
      jet/lobe, located at a significant distance away from the center of the Bullet
      cluster of galaxies.

PMID- 29208997
TI  - Experimental maturation of Archaea encrusted by Fe-phosphates.
AB  - Burial is generally detrimental to the preservation of biological signals. It has
      often been assumed that (bio)mineral-encrusted microorganisms are more resistant
      to burial-induced degradation than non-encrusted ones over geological timescales.
      For the present study, we submitted Sulfolobus acidocaldarius experimentally
      encrusted by amorphous Fe phosphates to constrained temperature conditions (150 
      degrees C) under pressure for 1 to 5 days, thereby simulating burial-induced
      processes. We document the molecular and mineralogical evolution of these
      assemblages down to the sub-micrometer scale using X-ray diffraction, scanning
      and transmission electron microscopies and synchrotron-based X-ray absorption
      near edge structure spectroscopy at the carbon K-edge. The present results
      demonstrate that the presence of Fe-phosphates enhances the chemical degradation
      of microbial organic matter. While Fe-phosphates remained amorphous in abiotic
      controls, crystalline lipscombite (FeIIxFeIII3-x(PO4)2(OH)3-x) entrapping organic
      matter formed in the presence of S. acidocaldarius cells. Lipscombite textures
      (framboidal vs. bipyramidal) appeared only controlled by the initial level of
      encrustation of the cells, suggesting that the initial organic matter to mineral
      ratio influences the competition between nucleation and crystal growth.
      Altogether these results highlight the important interplay between minerals and
      organic matter during fossilization, which should be taken into account when
      interpreting the fossil record.

PMID- 29208998
TI  - High Resolution AMS Dates from Shubayqa 1, northeast Jordan Reveal Complex
      Origins of Late Epipalaeolithic Natufian in the Levant.
AB  - The Late Epipalaeolithic Natufian (~14,600 - 11,500 cal BP) is a key period in
      the prehistory of southwest Asia. Often described as a complex hunting and
      gathering society with increased sedentism, intensive plant exploitation and
      associated with an increase in artistic and symbolic material culture, it is
      positioned between the earlier Upper- and Epi-Palaeolithic and the early
      Neolithic, when plant cultivation and subsequently animal domestication began.
      The Natufian has thus often been seen as a necessary pre-adaptation for the
      emergence of Neolithic economies in southwest Asia. Previous work has pointed to
      the Mediterranean woodland zone of the southern Levant as the 'core zone' of the
      Early Natufian. Here we present a new sequence of 27 AMS radiocarbon dates from
      the Natufian site Shubayqa 1 in northeast Jordan. The results suggest that the
      site was occupied intermittently between ~14,600 - 12,000 cal BP. The dates
      indicate the Natufian emerged just as early in eastern Jordan as it did in the
      Mediterranean woodland zone. This suggests that the origins and development of
      the Natufian were not tied to the ecological conditions of the Mediterranean
      woodlands, and that the evolution of this hunting and gathering society was more
      complex and heterogeneous than previously thought.

PMID- 29208999
TI  - Associations between childhood body size and seventeen adverse outcomes: analysis
      of 65,057 European women.
AB  - Large childhood body size has been consistently shown to be associated with
      decreased breast cancer risk. However, it is important to consider the effects of
      a large childhood body size on other adult diseases. It is not clear if the
      associations between childhood body size and adult diseases will persist if they
      later attain healthy weight. The associations between body size at age 7 and 17
      adverse outcomes in adulthood were examined using Cox models in a Swedish study
      of 65,057 women. Large body size at age 7, when compared to small body size, was
      associated with decreased risk for breast cancer (HR [95% CI]: 0.81 [0.70-0.93])
      and increased risks for anorexia (2.13 [1.63-2.77]) and bulimia (1.91 [1.35
      2.70]). Neither adjusting for adult BMI nor restricting the dataset to lean
      adults (BMI < 25 kg/m2) attenuated the associations. While large body size at age
      7 by itself was positively associated with increased risks of diabetes (1.34
      [1.16-1.55]), PCOS (1.69 [1.13-2.51]) and hypertension (before age 60), the
      associations were no longer significant after controlling for adult BMI. No clear
      associations were found with the remaining adverse outcomes (cervical, uterine,
      melanoma, colon cancer, depression, ovarian cyst, stroke, hyperlipidemia, heart
      failure, myocardial infarction, and angina pectoris).

PMID- 29209001
TI  - Remote tactile sensing system integrated with magnetic synapse.
AB  - Mechanoreceptors in a fingertip convert external tactile stimulations into
      electrical signals, which are transmitted by the nervous system through synaptic
      transmitters and then perceived by the brain with high accuracy and reliability.
      Inspired by the human synapse system, this paper reports a robust tactile sensing
      system consisting of a remote touch tip and a magnetic synapse. External pressure
      on the remote touch tip is transferred in the form of air pressure to the
      magnetic synapse, where its variation is converted into electrical signals. The
      developed system has high sensitivity and a wide dynamic range. The remote
      sensing system demonstrated tactile capabilities over wide pressure range with a
      minimum detectable pressure of 6 Pa. In addition, it could measure tactile
      stimulation up to 1,000 Hz without distortion and hysteresis, owing to the
      separation of the touching and sensing parts. The excellent performance of the
      system in terms of surface texture discrimination, heartbeat measurement from the
      human wrist, and satisfactory detection quality in water indicates that it has
      considerable potential for various mechanosensory applications in different
      environments.

PMID- 29209000
TI  - Deconvoluting the Photonic and Electronic Response of 2D Materials: The Case of
      MoS2.
AB  - Evaluating and tuning the properties of two-dimensional (2D) materials is a major
      focus of advancing 2D science and technology. While many claim that the photonic
      properties of a 2D layer provide evidence that the material is "high quality",
      this may not be true for electronic performance. In this work, we deconvolute the
      photonic and electronic response of synthetic monolayer molybdenum disulfide. We
      demonstrate that enhanced photoluminescence can be robustly engineered via the
      proper choice of substrate, where growth of MoS2 on r-plane sapphire can yield
      >100x enhancement in PL and carrier lifetime due to increased molybdenum-oxygen
      bonding compared to that of traditionally grown MoS2 on c-plane sapphire. These
      dramatic enhancements in optical properties are similar to those of super-acid
      treated MoS2, and suggest that the electronic properties of the MoS2 are also
      superior. However, a direct comparison of the charge transport properties
      indicates that the enhanced PL due to increased Mo-O bonding leads to p-type
      compensation doping, and is accompanied by a 2x degradation in transport
      properties compared to MoS2 grown on c-plane sapphire. This work provides a
      foundation for understanding the link between photonic and electronic performance
      of 2D semiconducting layers, and demonstrates that they are not always
      correlated.

PMID- 29209002
TI  - The orientation and stability of the GPCR-Arrestin complex in a lipid bilayer.
AB  - G protein-coupled receptors (GPCRs) constitute a large family of membrane
      proteins that plays a key role in transmembrane signal transduction and draw wide
      attention since it was discovered. Arrestin is a small family of proteins which
      can bind to GPCRs, block G protein interactions and redirect signaling to G
      protein-independent pathways. The detailed mechanism of how arrestin interacts
      with GPCR remains elusive. Here, we conducted molecular dynamics simulations with
      coarse-grained (CG) and all-atom (AA) models to study the complex structure
      formed by arrestin and rhodopsin, a prototypical GPCR, in a POPC bilayer. Our
      results indicate that the formation of the complex has a significant impact on
      arrestin which is tightly anchored onto the bilayer surface, while has a minor
      effect on the orientation of rhodopsin in the lipid bilayer. The formation of the
      complex induces an internal change of conformation and flexibility in both
      rhodopsin and arrestin, mainly at the binding interface. Further investigation on
      the interaction interface identified the hydrogen bond network, especially the
      long-lived hydrogen bonds, and the key residues at the contact interface, which
      are responsible for stabilizing the complex. These results help us to better
      understand how rhodopsin interacts with arrestin on membranes, and thereby shed
      lights on arrestin-mediated signal transduction through GPCRs.

PMID- 29209004
TI  - DNA nanotechnology: On-command molecular Trojans.

PMID- 29209005
TI  - Moore's deviation.

PMID- 29209006
TI  - Levitated nanoparticles: Nanoparticles jumping high.

PMID- 29209007
TI  - Reproducibility, sharing and progress in nanomaterial databases.

PMID- 29209003
TI  - Prostate cancer diagnosis and characterization with mass spectrometry imaging.
AB  - BACKGROUND: Prostate cancer (PCa), the most common cancer and second leading
      cause of cancer death in American men, presents the clinical challenge of
      distinguishing between indolent and aggressive tumors for proper treatment. PCa
      presents significant alterations in metabolic pathways that can potentially be
      measured using techniques like mass spectrometry (MS) or MS imaging (MSI) and
      used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic,
      and lipidomic profiles of biological systems that can be further visualized for
      their spatial distributions through MSI. METHODS: PubMed was queried for all
      publications relating to MS and MSI in human PCa from April 2007 to April 2017.
      With the goal of reviewing the utility of MSI in diagnosis and prognostication of
      human PCa, MSI articles that reported investigations of PCa-specific metabolites
      or metabolites indicating PCa aggressiveness were selected for inclusion.
      Articles were included that covered MS and MSI principles, limitations, and
      applications in PCa. RESULTS: We identified nine key studies on MSI in intact
      human prostate tissue specimens that determined metabolites which could either
      differentiate between benign and malignant prostate tissue or indicate PCa
      aggressiveness. These MSI-detected biomarkers show promise in reliably
      identifying PCa and determining disease aggressiveness. CONCLUSIONS: MSI
      represents an innovative technique with the ability to interrogate cancer
      biomarkers in relation to tissue pathologies and investigate tumor
      aggressiveness. We propose MSI as a powerful adjuvant histopathology imaging tool
      for prostate tissue evaluations, where clinical translation of this ex vivo
      technique could make possible the use of MSI for personalized medicine in
      diagnosis and prognosis of PCa. Moreover, the knowledge provided from this
      technique can majorly contribute to the understanding of molecular pathogenesis
      of PCa and other malignant diseases.

PMID- 29209008
TI  - How to build a nanotech company.

PMID- 29209009
TI  - Reply to 'On phonons and water flow enhancement in carbon nanotubes'.

PMID- 29209010
TI  - On phonons and water flow enhancement in carbon nanotubes.

PMID- 29209013
TI  - DNA nanotechnology: DNA robots that sort cargoes.

PMID- 29209011
TI  - The shortfall of risk assessment for decision-making.

PMID- 29209014
TI  - A MoTe2-based light-emitting diode and photodetector for silicon photonic
      integrated circuits.
AB  - One of the current challenges in photonics is developing high-speed, power
      efficient, chip-integrated optical communications devices to address the
      interconnects bottleneck in high-speed computing systems. Silicon photonics has
      emerged as a leading architecture, in part because of the promise that many
      components, such as waveguides, couplers, interferometers and modulators, could
      be directly integrated on silicon-based processors. However, light sources and
      photodetectors present ongoing challenges. Common approaches for light sources
      include one or few off-chip or wafer-bonded lasers based on III-V materials, but
      recent system architecture studies show advantages for the use of many directly
      modulated light sources positioned at the transmitter location. The most advanced
      photodetectors in the silicon photonic process are based on germanium, but this
      requires additional germanium growth, which increases the system cost. The
      emerging two-dimensional transition-metal dichalcogenides (TMDs) offer a path for
      optical interconnect components that can be integrated with silicon photonics and
      complementary metal-oxide-semiconductors (CMOS) processing by back-end-of-the
      line steps. Here, we demonstrate a silicon waveguide-integrated light source and
      photodetector based on a p-n junction of bilayer MoTe2, a TMD semiconductor with
      an infrared bandgap. This state-of-the-art fabrication technology provides new
      opportunities for integrated optoelectronic systems.

PMID- 29209015
TI  - Nanomaterials: 2D materials for silicon photonics.

PMID- 29209016
TI  - Direct measurement of Kramers turnover with a levitated nanoparticle.
AB  - Understanding the thermally activated escape from a metastable state is at the
      heart of important phenomena such as the folding dynamics of proteins, the
      kinetics of chemical reactions or the stability of mechanical systems. In 1940,
      Kramers calculated escape rates both in the high damping and low damping regimes,
      and suggested that the rate must have a maximum for intermediate damping. This
      phenomenon, today known as the Kramers turnover, has triggered important
      theoretical and numerical studies. However, as yet, there is no direct and
      quantitative experimental verification of this turnover. Using a nanoparticle
      trapped in a bistable optical potential, we experimentally measure the
      nanoparticle's transition rates for variable damping and directly resolve the
      Kramers turnover. Our measurements are in agreement with an analytical model that
      is free of adjustable parameters. The levitated nanoparticle presented here is a
      versatile experimental platform for studying and simulating a wide range of
      stochastic processes and testing theoretical models and predictions.

PMID- 29209017
TI  - New Hybrid Hydrazinyl Thiazole Substituted Chromones: As Potential alpha-Amylase
      Inhibitors and Radical (DPPH & ABTS) Scavengers.
AB  - Current research is based on the identification of novel inhibitors of alpha
      amylase enzyme. For that purpose, new hybrid molecules of hydrazinyl thiazole
      substituted chromones 5-27 were synthesized by multi-step reaction and fully
      characterized by various spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR
      and 13C-NMR. Stereochemistry of the iminic bond was confirmed by NOESY analysis
      of a representative molecule. All compounds 5-27 along with their intervening
      intermediates 1-4, were screened for in vitro alpha-amylase inhibitory, DPPH and
      ABTS radical scavenging activities. All compounds showed good inhibition
      potential in the range of IC50 = 2.186-3.405 uM as compared to standard acarbose
      having IC50 value of 1.9 +/- 0.07 uM. It is worth mentioning that compounds were
      also demonstrated good DPPH (IC50 = 0.09-2.233 uM) and ABTS (IC50 = 0.584-3.738
      uM) radical scavenging activities as compared to standard ascorbic acid having
      IC50 = 0.33 +/- 0.18 uM for DPPH and IC50 = 0.53 +/- 0.3 uM for ABTS radical
      scavenging activities. In addition to that cytotoxicity of the compounds were
      checked on NIH-3T3 mouse fibroblast cell line and found to be non-toxic. In
      silico studies were performed to rationalize the binding mode of compounds
      (ligands) with the active site of alpha-amylase enzyme.

PMID- 29209018
TI  - Novel Mechanism of the Pericyte-Myofibroblast Transition in Renal Interstitial
      Fibrosis: Core Fucosylation Regulation.
AB  - Pericytes have been identified as a major source of myofibroblasts in renal
      interstitial fibrosis (RIF). The overactivation of several signaling pathways,
      mainly the TGF-beta and PDGF pathways, initiates the pericyte-myofibroblast
      transition during RIF. Key receptors in these two pathways have been shown to be
      modified by fucosyltransferase 8 (FUT8), the enzyme that catalyzes core
      fucosylation. This study postulated that core fucosylation might play an
      important role in regulating the pericyte transition in RIF. The data showed that
      core fucosylation increased with the extent of RIF in patients with IgA
      nephropathy (IgAN). Similarly, core fucosylation of pericytes increased in both a
      unilateral ureteral occlusion (UUO) mouse model and an in vitro model of pericyte
      transition. Inhibition of core fucosylation by adenoviral-mediated FUT8 shRNA in
      vivo and FUT8 siRNA in vitro significantly reduced pericyte transition and RIF.
      In addition, the activation of both the TGF-beta/Smad and PDGF/ERK pathways was
      blocked by core fucosylation inhibition. In conclusion, core fucosylation may
      regulate the pericyte transition in RIF by modifying both the TGF-beta/Smad and
      PDGF/ERK pathways. Glycosylation might be a novel "hub" target to prevent RIF.

PMID- 29209019
TI  - Correlations between gut microbiota community structures of Tibetans and
      geography.
AB  - Microbial communities of human gut directly influence health and bear adaptive
      potential to different geography environment and lifestyles. However, knowledge
      about the influences of altitude and geography on the gut microbiota of Tibetans
      is currently limited. In this study, fecal microbiota from 208 Tibetans across
      six different locations were analyzed by MiSeq sequencing; these locations
      included Gannan, Gangcha, Tianzhu, Hongyuan, Lhasa and Nagqu, with altitudes
      above sea level ranging from 2800 m to 4500 m across the Tibetan plateau.
      Significant differences were observed in microbial diversity and richness in
      different locations. At the phylum level, gut populations of Tibetans comprised
      Bacteroidetes (60.00%), Firmicutes (29.04%), Proteobacteria (5.40%), and
      Actinobacteria (3.85%) and were marked by a low ratio (0.48) of Firmicutes to
      Bacteroidetes. Analysis based on operational taxonomic unit level revealed that
      core microbiotas included Prevotella, Faecalibacterium, and Blautia, whereas
      Prevotella predominated all locations, except Gangcha. Four community state types
      were detected in all samples, and they mainly belong to Prevotella, Bacteroides,
      and Ruminococcaceae. Principal component analysis and related correspondence
      analysis results revealed that bacterial profiles in Tibetan guts varied
      significantly with increasing altitude, BMI, and age, and facultative anaerobes
      were rich in Tibetan guts. Gut microbiota may play important roles in regulating
      high-altitude and geographical adaptations.

PMID- 29209021
TI  - Resolving the spin splitting in the conduction band of monolayer MoS2.
AB  - Time-reversal symmetry and broken spin degeneracy enable the exploration of spin
      and valley quantum degrees of freedom in monolayer transition-metal
      dichalcogenides. While the strength of the large spin splitting in the valance
      band of these materials is now well-known, probing the 10-100 times smaller
      splitting in the conduction band poses significant challenges. Since it is easier
      to achieve n-type conduction in most of them, resolving the energy levels in the
      conduction band is crucial for the prospect of developing new spintronic and
      valleytronic devices. Here, we study quantum transport in high mobility monolayer
      MoS2 devices where we observe well-developed quantized conductance in multiples
      of e 2/h in zero magnetic field. We extract a sub-band spacing energy of 0.8 meV.
      The application of a magnetic field gradually increases the interband spacing due
      to the valley-Zeeman effect. Here, we extract a g-factor of ~2.16 in the
      conduction band of monolayer MoS2.

PMID- 29209022
TI  - Microdroplet-based On-Demand Drawing of High Aspect-Ratio Elastomeric Micropillar
      and Its Contact Sensing Application.
AB  - High aspect-ratio elastomeric micropillars play important roles as the platform
      for microscale sensing and actuation. Many soft-lithographic techniques have been
      developed for their facile realization but most of the techniques are limited to
      build the micropillars only on totally flat, widely accessible substrate areas
      with the micropillar's structural characteristics completely predetermined,
      leaving little room for in situ control. Here we demonstrate a new technique
      which overcomes these limitations by directly drawing micropillars from pipette
      dispensed PDMS microdroplets using vacuum-chucked microspheres. The combined
      utilization of PDMS microdroplets and microspheres not only enables the
      realization of microsphere-tipped PDMS micropillars on non-flat, highly space
      constrained substrate areas at in situ controllable heights but also allows
      arraying of micropillars with dissimilar heights at a close proximity. To
      validate the new technique's utility and versatility, we realize PDMS
      micropillars on various unconventional substrate areas in various configurations.
      We also convert one of them, the optical fiber/micropillar hybrid, into a soft
      optical contact sensor. Both the fabrication technique and the resulting sensing
      scheme will be useful for future biomedical microsystems.

PMID- 29209020
TI  - A genotype-first approach identifies an intellectual disability-overweight
      syndrome caused by PHIP haploinsufficiency.
AB  - Genotype-first combined with reverse phenotyping has shown to be a powerful tool
      in human genetics, especially in the era of next generation sequencing. This
      combines the identification of individuals with mutations in the same gene and
      linking these to consistent (endo)phenotypes to establish disease causality. We
      have performed a MIP (molecular inversion probe)-based targeted re-sequencing
      study in 3,275 individuals with intellectual disability (ID) to facilitate a
      genotype-first approach for 24 genes previously implicated in ID.Combining our
      data with data from a publicly available database, we confirmed 11 of these 24
      genes to be relevant for ID. Amongst these, PHIP was shown to have an enrichment
      of disruptive mutations in the individuals with ID (5 out of 3,275). Through
      international collaboration, we identified a total of 23 individuals with PHIP
      mutations and elucidated the associated phenotype. Remarkably, all 23 individuals
      had developmental delay/ID and the majority were overweight or obese. Other
      features comprised behavioral problems (hyperactivity, aggression, features of
      autism and/or mood disorder) and dysmorphisms (full eyebrows and/or synophrys,
      upturned nose, large ears and tapering fingers). Interestingly, PHIP encodes two
      protein-isoforms, PHIP/DCAF14 and NDRP, each involved in neurodevelopmental
      processes, including E3 ubiquitination and neuronal differentiation. Detailed
      genotype-phenotype analysis points towards haploinsufficiency of PHIP/DCAF14, and
      not NDRP, as the underlying cause of the phenotype.Thus, we demonstrated the use
      of large scale re-sequencing by MIPs, followed by reverse phenotyping, as a
      constructive approach to verify candidate disease genes and identify novel
      syndromes, highlighted by PHIP haploinsufficiency causing an ID-overweight
      syndrome.

PMID- 29209023
TI  - Motor cortical activity changes during neuroprosthetic-controlled object
      interaction.
AB  - Brain-computer interface (BCI) controlled prosthetic arms are being developed to
      restore function to people with upper-limb paralysis. This work provides an
      opportunity to analyze human cortical activity during complex tasks. Previously
      we observed that BCI control became more difficult during interactions with
      objects, although we did not quantify the neural origins of this phenomena. Here,
      we investigated how motor cortical activity changed in the presence of an object
      independently of the kinematics that were being generated using intracortical
      recordings from two people with tetraplegia. After identifying a population-wide
      increase in neural firing rates that corresponded with the hand being near an
      object, we developed an online scaling feature in the BCI system that operated
      without knowledge of the task. Online scaling increased the ability of two
      subjects to control the robotic arm when reaching to grasp and transport objects.
      This work suggests that neural representations of the environment, in this case
      the presence of an object, are strongly and consistently represented in motor
      cortex but can be accounted for to improve BCI performance.

PMID- 29209024
TI  - Future loss of Arctic sea-ice cover could drive a substantial decrease in
      California's rainfall.
AB  - From 2012 to 2016, California experienced one of the worst droughts since the
      start of observational records. As in previous dry periods, precipitation
      inducing winter storms were steered away from California by a persistent
      atmospheric ridging system in the North Pacific. Here we identify a new link
      between Arctic sea-ice loss and the North Pacific geopotential ridge development.
      In a two-step teleconnection, sea-ice changes lead to reorganization of tropical
      convection that in turn triggers an anticyclonic response over the North Pacific,
      resulting in significant drying over California. These findings suggest that the
      ability of climate models to accurately estimate future precipitation changes
      over California is also linked to the fidelity with which future sea-ice changes
      are simulated. We conclude that sea-ice loss of the magnitude expected in the
      next decades could substantially impact California's precipitation, thus
      highlighting another mechanism by which human-caused climate change could
      exacerbate future California droughts.

PMID- 29209025
TI  - Oblique corpectomy in the cervical spine.
AB  - STUDY DESIGN: A narrative review. OBJECTIVES: A literature review of studies
      reporting on the application of oblique corpectomy (OC) in various pathologies of
      the cervical spine. SETTING: UK. METHODS: A search was carried out using the
      PubMed and Google Scholar up to 18 March 2017. Finally, 26 studies met the
      inclusion criteria. RESULTS: A multilevel OC shows good clinical outcomes in
      various pathologies in the cervical spine. The clinical improvement in cervical
      spondylotic myelopathy (CSM) and ossification of the posterior longitudinal
      ligament was found to be over 70%. OC allows wide anterior decompression of the
      spinal cord and complete unilateral nerve root decompression. The approach
      carries a risk of Horner's syndrome, vertebral artery and accessory nerve injury.
      OC does not compromise spine stability and osteoarthrodesis with bone grafting is
      not necessary. Spinal motions are preserved and appear close to normal. OC can be
      applied in patients with a low fusion rate such as the elderly, diabetics, and
      heavy smokers. Furthermore, OC was found to be an optimal approach for exta
      intradural tumors of the cervical spine. CONCLUSIONS: OC seems to be a valid
      alternative for the management of multisegmental CSM in selected cases. It should
      not be considered a first-line treatment strategy due to the relatively high
      morbidity. There are no studies comparing OC without fusion to other treatment
      options in CSM. Therefore, rigorous prospective studies using validated outcome
      measures with long-term follow-up are required.

PMID- 29209026
TI  - QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53
      signaling pathway.
AB  - The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the
      treatment of heart failure (HF) in China. Previous studies have shown that QSKL
      has definite effects on HF. The purpose of this study is to identify the
      regulation of QSKL on apoptosis and clarify the underlying mechanism. An
      apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery
      (OGD/R). An animal model of HF was induced by ligation of left anterior
      descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular
      ROS generation, increased mitochondrial membrane potential and protected H9C2
      cells against OGD/R-induced apoptosis. In vivo results showed that QSKL
      administration could improve cardiac functions, decrease fibrotic area, infarct
      size and apoptotic rate in HF model. QSKL regulated the expressions of key
      apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the
      expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated
      the phosphorylated expressions of PI3K and Akt without significantly affecting
      PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be
      mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.

PMID- 29209027
TI  - Shorter telomeres precede population extinction in wild lizards.
AB  - Identifying the early warning signals of catastrophic extinctions has recently
      become a central focus for ecologists, but species' functional responses to
      environmental changes remain an untapped source for the sharpening of such
      warning signals. Telomere length (TL) analysis represents a promising molecular
      tool with which to raise the alarm regarding early population decline, since
      telomere attrition is associated with aging processes and accelerates after a
      recurrent exposure to environmental stressors. In the southern margin of their
      range, populations of the common lizard (Zootoca vivipara) recently became
      extinct at lowest elevations due to changes in climate conditions. However, the
      proximal signals involved in these demographic declines are still unknown. Here,
      we sampled 100 yearling lizards from 10 natural populations (n = 10 per
      population) along an extinction risk gradient. Relative lizard abundance
      dramatically dropped over 12 years in low-altitude populations characterized by
      warmer ambient temperatures and higher body growth of lizards early in life. A
      non-linear relationship was found between TL and population extinction risk, with
      shorter telomeres in populations facing high risk of extinction when compared to
      non-threatened ones. Our results identify TL as a promising biomarker and imply
      that population extinctions might be preceded by a loop of physiological aging.

PMID- 29209028
TI  - Suitability of two distinct approaches for the high-throughput study of the post
      embryonic effects of embryo-lethal mutations in Arabidopsis.
AB  - Several hundred genes are required for embryonic and gametophytic development in
      the model plant Arabidopsis thaliana, as inferred from the lethality of their
      mutations. Despite many of these genes are expressed throughout the plant life
      cycle, the corresponding mutants arrest at early stages, preventing the study of
      their post-embryonic functions by conventional methods. Clonal analysis
      represents an effective solution to this problem by uncovering the effects of
      embryo-lethal mutations in sectors of mutant cells within an otherwise normal
      adult plant. In this pilot study, we have evaluated the suitability of two sector
      induction methods for the large-scale study of the post-embryonic effects of
      embryo-lethal (emb) mutations in Arabidopsis. In line with the interests of our
      laboratory, we selected 24 emb mutations that damage genes that are expressed in
      wild-type vegetative leaves but whose effects on leaf development remain unknown.
      For the induction of mutant sectors in adult plants, we followed one approach
      based on the X-ray irradiation of 'cell autonomy' (CAUT) lines, and another based
      on the site-specific excision of transgenes mediated by Cre recombinase. We
      conclude that both methods are time-consuming and difficult to scale up, being
      better suited for the study of emb mutations on a case-by-case basis.

PMID- 29209029
TI  - An in vitro assay to measure antibody-mediated inhibition of P. berghei
      sporozoite invasion against P. falciparum antigens.
AB  - A large research effort is currently underway to find an effective and affordable
      malaria vaccine. Tools that enable the rapid evaluation of protective immune
      responses are essential to vaccine development as they can provide selection
      criteria to rank order vaccine candidates. In this study we have revisited the
      Inhibition of Sporozoite Invasion (ISI) assay to assess the ability of antibodies
      to inhibit sporozoite infection of hepatocytes. By using GFP expressing
      sporozoites of the rodent parasite P. berghei we are able to robustly quantify
      parasite infection of hepatocyte cell lines by flow cytometry. In conjunction
      with recently produced transgenic P. berghei parasites that express P. falciparum
      sporozoite antigens, we have been able to use this assay to measure antibody
      mediated inhibition of sporozoite invasion against one of the lead malaria
      antigens P. falciparum CSP. By combining chimeric rodent parasites expressing P.
      falciparum antigens and a flow cytometric readout of infection, we are able to
      robustly assess vaccine-induced antibodies, from mice, rhesus macaques and human
      clinical trials, for their functional ability to block sporozoite invasion of
      hepatocytes.

PMID- 29209030
TI  - High-hole mobility polycrystalline Ge on an insulator formed by controlling
      precursor atomic density for solid-phase crystallization.
AB  - High-carrier mobility semiconductors on insulators are essential for fabricating
      advanced thin-film transistors, allowing for three-dimensional integrated
      circuits or high-performance mobile terminals. We investigate the low-temperature
      (375-450  degrees C) solid-phase crystallization (SPC) of Ge on a glass
      substrate, focusing on the precursor conditions. The substrate temperature during
      the precursor deposition, T d, ranged from 50 to 200  degrees C. According to the
      atomic density of the precursor and the T d dependent SPC properties, the
      precursor conditions were determined by three regimes: the low-density regime (T
      d < 100  degrees C), high-density regime (100 <= T d <= 125  degrees C), and
      nucleation regime (T d > 125  degrees C). The use of the precursor in the narrow
      high-density regime enabled us to form SPC-Ge with a hole mobility of 340 cm2/Vs,
      the highest value among semiconductor thin films grown on insulators at low
      temperature (<900  degrees C). The origins of the high hole mobility were
      determined to be both a large grain size (5 um) and a low energy barrier height
      (6.4 meV) for the grain boundary. The findings from and knowledge gained in this
      study, that is, the influence of the precursor conditions on subsequent crystal
      growth, will be universal and applicable to various materials.

PMID- 29209031
TI  - Racial differences in neonatal hypoglycemia among very early preterm births.
AB  - OBJECTIVE: To determine whether the prevalence of neonatal hypoglycemia differs
      by race/ethnicity. STUDY DESIGN: A retrospective cohort study using prospectively
      collected data from 515 neonates born very preterm (<32 weeks) to normoglycemic
      women and admitted to the neonatal intensive care unit (NICU) at a major tertiary
      hospital in Boston, MA, between 2008 and 2012. RESULTS: A total of 61%, 12%, 7%,
      7%, and 13% were White, Black, Hispanic, Asian, and Other, respectively. Among
      the 66% spontaneous preterm births, 63% of the black neonates experienced
      hypoglycemia (blood glucose level < 40 mg/dL), while only 22-30% of the other
      racial/ethnic neonates did so (Black vs. White RR 2.15; 95% CI: 1.54-3.00). After
      adjusting for maternal education, maternal age, multiple gestations, delivery
      type, gestational age, birth weight, and neonates' sex, this association remained
      significant (adjusted Black vs. White RR: 1.61, 95% CI: 1.13-2.29). An increased
      risk of infant hypoglycemia was not seen in infants of other racial/ethnic
      groups, nor in any racial/ethnic group with a medically indicated preterm birth.
      CONCLUSIONS: Black neonates delivered for spontaneous (but not medical)
      indications at <32 weeks had a higher risk of hypoglycemia, which could provide
      critical information about mechanisms of preterm birth and adverse postnatal
      outcomes in this high-risk group.

PMID- 29209032
TI  - Comparison of state risk-appropriate neonatal care policies with the 2012 AAP
      policy statement.
AB  - OBJECTIVE: Compare state policies with standards outlined in the 2012 AAP Policy
      Statement on Levels of Neonatal Care. STUDY DESIGN: Systematic, web-based review
      of publicly available policies on levels of care in all states in 2014. Infant
      risk information, equipment capabilities, and specialty staffing were abstracted
      from published rules, statutes, and regulations. RESULT: Twenty-two states had a
      policy on regionalized perinatal care. State policies vary in consistency with
      the AAP Policy, with 60% of states including standards consistent with Level I
      criteria, 48% Level II, 14% Level III, and one state with Level IV. Ventilation
      capability standards are highly consistent (66-100%), followed by imaging
      capability standards (50-90%). Policy language on specialty staffing (44-68%),
      and subspecialty staffing (39-50%) are moderately consistent. CONCLUSION: State
      policies vary in consistency, a potentially significant barrier to monitoring,
      regulation, uniform care provision and measurement, and reporting of national
      level measures on risk-appropriate care.

PMID- 29209033
TI  - Study of THz-Plasmon hybridization of a loop Yagi-Uda absorber.
AB  - In this article we present a three-dimensional loop Yagi-Uda array for efficient,
      polarization independent and directional absorption of THz radiation over a
      narrow frequency range (f0 = 0.657 THz & Q factor = 7.5). Unit cell of the array
      consists of three vertically stacked gold micro rings separated from each other
      by 30 um thick SU-8 layers. The proposed array also exhibits a filtering response
      in its transmittance spectrum. The characteristics are explained by plasmon
      hybridization method. The transmission, reflection and absorption spectra of the
      structure are measured and they show a good agreement with corresponding
      simulated results.

PMID- 29209034
TI  - Na+ entry through heteromeric TRPC4/C1 channels mediates (-)Englerin A-induced
      cytotoxicity in synovial sarcoma cells.
AB  - The sesquiterpene (-)Englerin A (EA) is an organic compound from the plant
      Phyllanthus engleri which acts via heteromeric TRPC4/C1 channels to cause
      cytotoxicity in some types of cancer cell but not normal cells. Here we
      identified selective cytotoxicity of EA in human synovial sarcoma cells (SW982
      cells) and investigated the mechanism. EA induced cation channel current (Icat)
      in SW982 cells with biophysical characteristics of heteromeric TRPC4/C1 channels.
      Inhibitors of homomeric TRPC4 channels were weak inhibitors of the Icat and EA
      induced cytotoxicity whereas a potent inhibitor of TRPC4/C1 channels (Pico145)
      strongly inhibited Icat and cytotoxicity. Depletion of TRPC1 converted Icat into
      a current with biophysical and pharmacological properties of homomeric TRPC4
      channels and depletion of TRPC1 or TRPC4 suppressed the cytotoxicity of EA. A
      Na+/K+-ATPase inhibitor (ouabain) potentiated EA-induced cytotoxicity and direct
      Na+ loading by gramicidin-A caused Pico145-resistant cytotoxicity in the absence
      of EA. We conclude that EA has a potent cytotoxic effect on human synovial
      sarcoma cells which is mediated by heteromeric TRPC4/C1 channels and Na+ loading.

PMID- 29209035
TI  - Disturbed blood flow worsens endothelial dysfunction in moderate-severe chronic
      obstructive pulmonary disease.
AB  - The aims of this study were: (1) to test whether oscillatory shear stress further
      exacerbates endothelial dysfunction in patients with moderate-severe COPD, and
      (2) to test whether low flow oxygen administration improves endothelial function
      and is protective against oscillatory shear stress-induced endothelial
      dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age
      matched non-smoking control subjects we examined brachial artery flow-mediated
      dilation (FMD) and circulating microparticles before and after 20 minutes of
      experimentally-induced oscillatory shear stress. COPD patients performed this
      intervention a second time following a 20-minute wash in period of low flow
      supplemental oxygen to normalize arterial oxygen saturation. COPD patients had
      ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P <
      0.05). The oscillatory shear stress intervention induced significant decreases in
      brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated
      circulating markers of endothelial cell apoptosis (CD31+/CD41b- microparticles)
      in COPD patients, but not age-matched controls. Supplemental oxygen
      administration abrogated the oscillatory shear stress-induced increase in
      CD31+/CD41b- microparticles, and improved FMD after accounting for the shear
      stress stimulus. We have demonstrated that acutely disturbed blood flow with
      increased retrograde shear stress further deteriorates the already impaired
      endothelial function with attendant endothelial apoptosis in patients with
      moderate-severe COPD.

PMID- 29209036
TI  - A Universal 3D Voxel Descriptor for Solid-State Material Informatics with Deep
      Convolutional Neural Networks.
AB  - Material informatics (MI) is a promising approach to liberate us from the time
      consuming Edisonian (trial and error) process for material discoveries, driven by
      machine-learning algorithms. Several descriptors, which are encoded material
      features to feed computers, were proposed in the last few decades. Especially to
      solid systems, however, their insufficient representations of three
      dimensionality of field quantities such as electron distributions and local
      potentials have critically hindered broad and practical successes of the solid
      state MI. We develop a simple, generic 3D voxel descriptor that compacts any
      field quantities, in such a suitable way to implement convolutional neural
      networks (CNNs). We examine the 3D voxel descriptor encoded from the electron
      distribution by a regression test with 680 oxides data. The present scheme
      outperforms other existing descriptors in the prediction of Hartree energies that
      are significantly relevant to the long-wavelength distribution of the valence
      electrons. The results indicate that this scheme can forecast any functionals of
      field quantities just by learning sufficient amount of data, if there is an
      explicit correlation between the target properties and field quantities. This 3D
      descriptor opens a way to import prominent CNNs-based algorithms of supervised,
      semi-supervised and reinforcement learnings into the solid-state MI.

PMID- 29209037
TI  - Bacteriophage T5 tail tube structure suggests a trigger mechanism for
      Siphoviridae DNA ejection.
AB  - The vast majority of phages, bacterial viruses, possess a tail ensuring host
      recognition, cell wall perforation and safe viral DNA transfer from the capsid to
      the host cytoplasm. Long flexible tails are formed from the tail tube protein
      (TTP) polymerised as hexameric rings around and stacked along the tape measure
      protein (TMP). Here, we report the crystal structure of T5 TTP pb6 at 2.2 A
      resolution. Pb6 is unusual in forming a trimeric ring, although structure
      analysis reveals homology with all classical TTPs and related tube proteins of
      bacterial puncturing devices (type VI secretion system and R-pyocin). Structures
      of T5 tail tubes before and after interaction with the host receptor were
      determined by cryo-electron microscopy at 6 A resolution. Comparison of these two
      structures reveals that host-binding information is not propagated to the capsid
      through conformational changes in the tail tube, suggesting a role of the TMP in
      this information transduction process.

PMID- 29209038
TI  - A simple method to assess group difference in RT-qPCR reference gene selection
      using GeNorm: The case of the placental sex.
AB  - Normalization with proper reference genes is a crucial step in obtaining accurate
      mRNA expression levels in RT-qPCR experiments. GeNorm and NormFinder are two
      commonly used software packages that help in selecting the best reference genes,
      based on their expression stability. However, GeNorm does not take into account a
      group variable, such as sample sex, in its calculation. We demonstrate a simple
      calculation step to assess the variability of such parameters by multiplying the
      GeNorm M value with the difference of Cq values between groups. To test this, we
      used 28 reference gene candidates, to analyze 20 placental samples (10 of each
      sex), and by using HPRT1 (lower Cq values in male placentas (P = 0.017)), as a
      target gene. Our calculation demonstrates that the RPL30 - GAPDH reference gene
      combination is the better option to assess small placental sex differences in
      mRNA level, versus the selection obtained from GeNorm or NormFinder. The HPRT1
      normalized mRNA expression level is different between placental sexes, using
      RPL30 and GAPDH as reference genes (P = 0.01), but not when using genes suggested
      by GeNorm or NormFinder. These results indicate that the proposed calculation is
      appropriate to assess small variations in mRNA expression between 2 groups.

PMID- 29209039
TI  - Author Correction: Tyrosine dephosphorylated cortactin downregulates
      contractility at the epithelial zonula adherens through SRGAP1.
AB  - A correction to this article has been published and is linked from the HTML
      version of this article.

PMID- 29209040
TI  - Chitosan coated cotton cloth supported zero-valent nanoparticles: Simple but
      economically viable, efficient and easily retrievable catalysts.
AB  - A simple, economically viable and fast method has been utilized for the
      preparation of highly active metal nanoparticles (MNPs) in coating layer of
      chitosan (CH) over cellulose microfibers of cotton cloth (CC). 2 wt% of CH
      solution was used for the coating of CC strips (CC-CH), and were kept in aqueous
      solutions of metal salts to adsorb metal ions. The CC-CH templated with metal
      ions were then treated with aqueous solution of NaBH4 to reduce the metal ions
      into zero-valent metal nanoparticles (M0). The CC-CH strips loaded with M0 were
      characterized by XRD, XPS, ATR-FTIR, FE-SEM and TGA, which indicates the
      successful synthesis of MNPs by this method. The M0/CC-CH strips were used as an
      efficient catalyst for the model reduction reaction of nitrophenol and toxic
      organic dyes. Among all the prepaped samples, Fe/CC-CH showed good catalytic
      activity for 4-NP and Rh-B dye reduction in the presence of NaBH4 with rate
      constants of 0.2937 min-1 and 0.3804 min-1, respectively. Moreover Fe/CC-CH has
      good catalytic reduction ability for MO and MB having rate constants equal to
      0.1698 and 0.2802 min-1, respectively. Beside the good catalytic ability, it
      could be easily recoverable as compared to other available techniques. The
      recovery was completed by simply pulling the strip from the reaction matrix after
      completion of the reaction and can be used several times.

PMID- 29209041
TI  - The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia.
AB  - The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the
      maintenance of different types of epithelial cancers. The role of WW domain
      containing E3 ubiquitin protein ligase 1 (WWP1) in haematological neoplasms
      remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion
      of malignant myeloid cells blocked at different stages of differentiation. Here
      we report that the expression of WWP1 is significantly augmented in a large
      cohort of primary AML patients and in AML cell lines, compared with
      haematopoietic cells from healthy donors. We show that WWP1 inactivation severely
      impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we
      observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon
      transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation
      induces the accumulation of its protein substrate p27Kip1, which ultimately
      contributes to G0/G1 cell cycle arrest of AML blasts. In addition, WWP1 depletion
      triggers the autophagy signalling and reduces survival of leukaemic cells.
      Collectively, our findings provide molecular insights into the anti-cancer
      potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker
      and druggable target in AML.

PMID- 29209042
TI  - Analysis of the genomic landscape of multiple myeloma highlights novel prognostic
      markers and disease subgroups.
AB  - In multiple myeloma, next generation sequencing (NGS) has expanded our knowledge
      of genomic lesions, and highlighted a dynamic and heterogeneous composition of
      the tumor. Here, we used NGS to characterize the genomic landscape of 418
      multiple myeloma cases at diagnosis and correlate this with prognosis and
      classification. Translocations and copy number changes (CNAs) had a preponderant
      contribution over gene mutations in defining the genotype and prognosis of each
      case. Known and novel independent prognostic markers were identified in our
      cohort of proteasome inhibitor and IMiD-treated patients with long follow-up,
      including events with context-specific prognostic value, such as deletions of the
      PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each
      case, we used innovative statistical approaches to identify potential novel
      myeloma subgroups. We observed clusters of patients stratified based on the
      overall number of mutations and number/type of CNAs, with distinct effects on
      survival, suggesting that extended genotype of multiple myeloma at diagnosis may
      lead to improved disease classification and prognostication.Leukemia accepted
      article preview online, 06 December 2017. doi:10.1038/leu.2017.344.

PMID- 29209043
TI  - CRISPR/Cas9-edited NSG mice as PDX models of human leukemia to address the role
      of niche-derived SPARC.

PMID- 29209044
TI  - Biological and prognostic impact of APOBEC-induced mutations in the spectrum of
      plasma cell dyscrasias and multiple myeloma cell lines.

PMID- 29209047
TI  - IBD in 2017: Development of therapy for and prediction of IBD - getting personal.

PMID- 29209045
TI  - MiR-211 is essential for adult cone photoreceptor maintenance and visual
      function.
AB  - MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression
      that play an important role in the control of fundamental biological processes in
      both physiological and pathological conditions. Their function in retinal cells
      is just beginning to be elucidated, and a few have been found to play a role in
      photoreceptor maintenance and function. MiR-211 is one of the most abundant
      miRNAs in the developing and adult eye. However, its role in controlling
      vertebrate visual system development, maintenance and function so far remain
      incompletely unexplored. Here, by targeted inactivation in a mouse model, we
      identify a critical role of miR-211 in cone photoreceptor function and survival.
      MiR-211 knockout (-/-) mice exhibited a progressive cone dystrophy accompanied by
      significant alterations in visual function. Transcriptome analysis of the retina
      from miR-211-/- mice during cone degeneration revealed significant alteration of
      pathways related to cell metabolism. Collectively, this study highlights for the
      first time the impact of miR-211 function in the retina and significantly
      contributes to unravelling the role of specific miRNAs in cone photoreceptor
      function and survival.

PMID- 29209048
TI  - Gut microbiota: A mother's microbiota: intergenerational transfer.

PMID- 29209046
TI  - Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN
      complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.
AB  - Cdc7-Dbf4 kinase plays a key role in the initiation of DNA replication and
      contributes to the replication stress in cancer. The activity of human Cdc7-Dbf4
      kinase remains active and acts as an effector of checkpoint under replication
      stress. However, the downstream targets of Cdc7-Dbf4 contributed to checkpoint
      regulation and replication stress-support function in cancer are not fully
      identified. In this work, we showed that aberrant Cdc7-Dbf4 induces DNA lesions
      that activate ATM/ATR-mediated checkpoint and homologous recombination (HR) DNA
      repair. Using a phosphoproteome approach, we identified HSP90-S164 as a target of
      Cdc7-Dbf4 in vitro and in vivo. The phosphorylation of HSP90-S164 by Cdc7-Dbf4 is
      required for the stability of HSP90-HCLK2-MRN complex and the function of ATM/ATR
      signaling cascade and HR DNA repair. In clinically, the phosphorylation of HSP90
      S164 indeed is increased in oral cancer patients. Our results indicate that
      aberrant Cdc7-Dbf4 enhances replication stress tolerance by rewiring ATR/ATM
      mediated HR repair through HSP90-S164 phosphorylation and by promoting recovery
      from replication stress. We provide a new solution to a subtyping of cancer
      patients with dominant ATR/HSP90 expression by combining inhibitors of ATR-Chk1,
      HSP90, or Cdc7 in cancer combination therapy.

PMID- 29209049
TI  - Repurposing an inhibitor of ribosomal biogenesis with broad anti-fungal activity.
AB  - The lack of new antifungal compounds with unique mechanisms of action is a
      concern for therapeutic management of patients. To identify inhibitors against
      human pathogenic fungi, we screened ~3000 compounds provided by the Developmental
      Therapeutics Program of NIH/NCI against a panel of pathogenic fungi including
      Candida species, Aspergillus fumigatus, and Cryptococcus neoformans. NSC319726 (a
      thiosemicarbazone) had broad antifungal activity in the range of 0.1-2.0 ug/ml
      and was also inhibitory to fluconazole-resistant isolates of Candida species.
      Synergy was demonstrated with NSC319726 and azoles, as well as caspofungin. The
      inhibitory concentration 50% (IC50) of NSC319726 was 35-800-fold higher than the
      Minimum Inhibitory Concentration 50% (MIC50 values), which indicates low compound
      toxicity to human cells in vitro. Transcriptome analysis of treated and untreated
      C. albicans using Gene Ontology (GO) revealed a large cluster of down regulated
      genes that encode translational proteins, especially those with ribosome
      biogenesis functions. As NSC319726 was first shown to have anti-cancer activity,
      its affects against human pathogenic fungi establish NSC319726 as a repurposed,
      off-patent compound that has potential antifungal activity. The minimal in vitro
      toxicity of lead optimized NSC319726 and its reasonable inhibitory activity
      against pathogens suggest advancing this compound to in vivo toxicity testing and
      protection studies against candidiasis.

PMID- 29209050
TI  - Publisher Correction: Method to Reduce Long-lived Fission Products by Nuclear
      Transmutations with Fast Spectrum Reactors.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29209051
TI  - Author Correction: Identification of functional tetramolecular RNA G-quadruplexes
      derived from transfer RNAs.
AB  - The original version of this Article contained an error in the spelling of the
      author Steven M. Coyne, which was incorrectly given as Stephen M. Coyne. This has
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 29209052
TI  - Maintaining pH-dependent conformational flexibility of M1 is critical for
      efficient influenza A virus replication.
AB  - The M gene segment of influenza A virus has been shown to be a contributing
      factor to the high growth phenotype. However, it remains largely unknown why
      matrix protein 1 (M1), the major structural protein encoded by M gene, exhibits
      pH-dependent conformational changes during virus replication. Understanding the
      mechanisms underlying efficient virus replication can help to develop strategies
      not only to combat influenza infections but also to improve vaccine supplies.
      M(NLS-88R) and M(NLS-88E) are two M1 mutants differing by only a single amino
      acid: G88R vs G88E. G88R but not G88E was the compensatory mutation naturally
      selected by the virus after its nuclear localization signal was disrupted. Our
      study shows that, compared with M(NLS-88E) M1, M(NLS-88R) M1 dissociated quickly
      from viral ribonucleoproteins (vRNPs) at higher pH and took less time to
      dissemble in vitro, despite forming thicker matrix layer and having stronger
      association with vRNP in assembled virions. Correspondingly, M(NLS-88R)
      replicated more efficiently and was genetically more stable than M(NLS-88E).
      Crystallographic analysis indicated that M(NLS-88R) M1, like wild-type M1, is
      able to switch from a face-to-back-oriented conformation to a face-to-face
      oriented conformation when pH drops from neutral to acidic, whereas G88E mutation
      causes M(NLS-88E) M1 to be trapped in a face-to-face-arranged conformation
      regardless of environmental pH. Our results suggest that maintaining M1 pH
      dependent conformational flexibility is critical for efficient virus replication,
      and position 88 is a key residue controlling M1 pH-dependent conformational
      changes. Our findings provide insights into developing M1-based antiviral agents.

PMID- 29209053
TI  - Development of an influenza virus protein microarray to measure the humoral
      response to influenza virus infection in mallards.
AB  - Avian influenza viruses pose a serious zoonotic threat, in part because current
      seasonal influenza virus vaccines only offer strain-specific protection, instead
      of heterosubtypic or universal protection against influenza virus infection.
      Understanding the humoral response to vaccination and natural infection in the
      broadest context possible is important to developing defenses against influenza
      zoonosis. Protein microarrays are a novel platform well suited to assaying the
      humoral immune response broadly and efficiently. We developed an influenza virus
      protein microarray (IVPM) that could be used to assay sera from many species,
      including humans. Waterfowl such as mallard ducks are natural reservoirs for many
      influenza A viruses, but their humoral immune response to infection is poorly
      understood. To establish this technology, we assayed sera from mallards
      experimentally infected with two low-pathogenic common avian influenza viruses
      (H3N8 and H4N5) for reactivity to influenza virus hemagglutinin (HA) by IVPM. The
      IVPM results correlated well with results from an established enzyme-linked
      immunosorbent assay, supporting the validity of the IVPM as a serological assay
      in influenza virus research. Interestingly, successive infection with H3N8
      followed by H4N5 virus in mallard ducks induced antibodies that were broadly
      reactive against group 2 hemagglutinins. We also analyzed sera from wild mallards
      and observed serological evidence for infection in those sera. With serological
      information, it may be possible to infer infection history of wild avian species
      and gain a better understanding of the infection dynamics of influenza viruses in
      their natural reservoir. This might ultimately lead to interventions that enhance
      our pandemic preparedness.

PMID- 29209055
TI  - Splicing: Going in circles.

PMID- 29209054
TI  - Triazole phenotypes and genotypic characterization of clinical Aspergillus
      fumigatus isolates in China.
AB  - This study investigated the triazole phenotype and genotypic of clinical
      Aspergillus fumigatus isolates from China. We determined the triazole
      susceptibility profiles of 159 A. fumigatus isolates collected between 2011 and
      2015 from four different areas in China tested against 10 antifungal drugs using
      the Clinical Laboratory Standard Institute M38-A2 method. For the seven
      itraconazole-resistant A. fumigatus isolates identified in the study, the cyp51A
      gene, including its promoter region, was sequenced and the mutation patterns were
      characterized. The resistant isolates were genotyped by microsatellite typing to
      determine the genetic relatedness to isolates from China and other countries. The
      frequency of itraconazole resistance in A. fumigatus isolates in our study was
      4.4% (7/159). Six of the seven triazole-resistant isolates were recovered from
      the east and southeast of China, and one from was recovered from the west of
      China. No resistant isolates were found in the north. Three triazole-resistant
      isolates exhibited the TR34/L98H mutation, two carried the TR34/L98H/S297T/F495I
      mutation and one harbored a G54V mutation in the cyp51A gene. Analysis of the
      microsatellite markers from seven non-wild-type isolates indicated the presence
      of five unique genotypes, which clustered into two major genetic groups. The
      cyp51A gene mutations TR34/L98H and TR34/L98H/S297T were the most frequently
      found mutations, and the G54V mutation was reported for the first time in China.
      The geographic origin of the triazole-resistant isolates appeared to concentrate
      in eastern and south-eastern areas, which suggests that routine antifungal
      susceptibility testing in these areas should be performed for all clinically
      relevant A. fumigatus isolates to guide antifungal therapy and for
      epidemiological purposes.

PMID- 29209057
TI  - Publisher Correction: Recycled iron fuels new production in the eastern
      equatorial Pacific Ocean.
AB  - The original version of this Article contained errors in Fig. 2b and Table 2. In
      Fig. 2b, the white circle labels were incorrectly positioned as they referred to
      scenarios that were used in an earlier version of the Article. In Table 2, the
      following three sentences were removed from the legend 'The last two calculations
      are discussed in the "Methods". The first assumes that all dissolved plus the
      ~0.3 nmol kg-1 of particulate iron (measured in the eastern equatorial Pacific30)
      is bioavailable. The last calculation assumes EUC dissolved iron concentrations
      from 140 degrees  W'. These errors have now been corrected in both the PDF and
      HTML versions of the Article.

PMID- 29209056
TI  - Transcription regulation by the Mediator complex.
AB  - Alterations in the regulation of gene expression are frequently associated with
      developmental diseases or cancer. Transcription activation is a key phenomenon in
      the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase
      II transcription (Mediator), a large complex with modular organization, is
      generally required for transcription by RNA polymerase II, and it regulates
      various steps of this process. The main function of Mediator is to transduce
      signals from the transcription activators bound to enhancer regions to the
      transcription machinery, which is assembled at promoters as the preinitiation
      complex (PIC) to control transcription initiation. Recent functional studies of
      Mediator with the use of structural biology approaches and functional genomics
      have revealed new insights into Mediator activity and its regulation during
      transcription initiation, including how Mediator is recruited to transcription
      regulatory regions and how it interacts and cooperates with PIC components to
      assist in PIC assembly. Novel roles of Mediator in the control of gene expression
      have also been revealed by showing its connection to the nuclear pore and linking
      Mediator to the regulation of gene positioning in the nuclear space. Clear links
      between Mediator subunits and disease have also encouraged studies to explore
      targeting of this complex as a potential therapeutic approach in cancer and
      fungal infections.

PMID- 29209058
TI  - Learning the value of information and reward over time when solving exploration
      exploitation problems.
AB  - To flexibly adapt to the demands of their environment, animals are constantly
      exposed to the conflict resulting from having to choose between predictably
      rewarding familiar options (exploitation) and risky novel options, the value of
      which essentially consists of obtaining new information about the space of
      possible rewards (exploration). Despite extensive research, the mechanisms that
      subtend the manner in which animals solve this exploitation-exploration dilemma
      are still poorly understood. Here, we investigate human decision-making in a
      gambling task in which the informational value of each trial and the reward
      potential were separately manipulated. To better characterize the mechanisms that
      underlined the observed behavioural choices, we introduce a computational model
      that augments the standard reward-based reinforcement learning formulation by
      associating a value to information. We find that both reward and information
      gained during learning influence the balance between exploitation and
      exploration, and that this influence was dependent on the reward context. Our
      results shed light on the mechanisms that underpin decision-making under
      uncertainty, and suggest new approaches for investigating the exploration
      exploitation dilemma throughout the animal kingdom.

PMID- 29209059
TI  - Fabrication and characterization of reversible thermochromic wood veneers.
AB  - Leuco dyes are widely used as functional materials for their thermosensitive
      chromogenic nature. The influences of thermochromic compounds and impregnation
      processing conditions on thermochromic wood veneer properties were investigated
      in this paper. The thermochromic compounds included thermochromic dye (ODB-2),
      color developer (bisphenol A) and solvent (1-tetradecanol). To achieve the
      maximum color change, the optimum mixing ratio of ODB-2 to bisphenol A to 1
      tetradecanol was 1:2:60. Juglans mandshurica veneers were ultrasonically
      impregnated with reversible thermochromic compound suspensions. Analysis of
      variance showed that the influences of impregnation parameters on veneer color
      change were significant at the 0.05 level. The optimum thermochromic wood veneer
      can be obtained by impregnating with a thermochromic compound suspension for 2.0
      min at 65  degrees C. In this paper, the thermochromic properties of wood veneers
      were evaluated, and functional thermochromic veneers exhibited excellent
      properties and thermostability.

PMID- 29209060
TI  - ATR-FTIR spectral discrimination between normal and tumorous mouse models of
      lymphoma and melanoma from serum samples.
AB  - This study presents, attenuated total reflection Fourier transforms infrared
      spectroscopy of dried serum samples in an effort to assess biochemical changes
      induced by non-Hodgkin's lymphoma and subcutaneous melanoma. An EL4 mouse model
      of non-Hodgkin lymphoma and a B16 mouse model of subcutaneous melanoma are used
      to extract a snapshot of tumor-associated alteration in the serum. The study of
      both cancer-bearing mouse models in wild types and their corresponding control
      types, emphasizes the diagnostic potential of this approach as a screening
      technique for non-Hodgkin lymphoma and melanoma skin cancer. Infrared absorbance
      values of the different spectral bands, hierarchical clustering and integral
      values of the component bands by curve fitting, show statistically significant
      differences (student's t-test, two-tailed unequal variance p-value < 0.05)
      between spectra representing healthy and tumorous mouse. This technique may thus
      be useful for having individualized route maps for rapid evaluation of lymphoma
      and melanoma status and associated therapeutic modalities.

PMID- 29209061
TI  - CAR-T cells: the narrow path between hope and bankruptcy?

PMID- 29209062
TI  - Jon van Rood (1926-2017).

PMID- 29209063
TI  - Effect of different organic fertilizers application on growth and environmental
      risk of nitrate under a vegetable field.
AB  - The effect of chicken manure after different disposal methods (water-logged
      composting, GOF; anaerobic digestion, BR; thermophilic composting, ROF) on
      vegetable growth and environmental risk was investigated under the tomato-celery
      tomato field. Results showed that organic fertilizers significantly increased
      vegetable yield and quality, but with inappropriate application may cause serious
      environmental risk such as nitrate pollution. Maximum vegetable yield of 80.9,
      68.3, 112.7 t.ha-1 (first, second and third rotation crop, respectively) with
      best vegetable quality was obtained in ROF treatment. The highest N use
      efficiency with the least nitrate enrichment in soil was also found in ROF
      treatment. Moreover, under this fertilization way, nitrate concentration in soil
      leachate dropped to 6.4 mg.L-1, which satisfied the threshold (<10 mg.L-1) for
      drinking water set by the US Environmental Protection Agency. Thus, ROF was
      suggested to be the optimal fertilizer with the best yield, quality and the least
      environmental risk under the "tomato-celery" rotation system.

PMID- 29209064
TI  - Magnetic field observations in CoFeB/Ta layers with 0.67-nm resolution by
      electron holography.
AB  - Nanometre-scale magnetic field distributions in materials such as those at oxide
      interfaces, in thin layers of spintronics devices, and at boundaries in magnets
      have become important research targets in materials science and applied physics.
      Electron holography has advantages in nanometric magnetic field observations, and
      the realization of aberration correctors has improved its spatial resolution.
      Here we show the subnanometre magnetic field observations inside a sample at 0.67
      nm resolution achieved by an aberration-corrected 1.2-MV holography electron
      microscope with a pulse magnetization system. A magnetization reduction due to
      intermixing in a CoFeB/Ta multilayer is analyzed by observing magnetic field and
      electrostatic potential distributions simultaneously. Our results demonstrate
      that high-voltage electron holography can be widely applied to pin-point
      magnetization analysis with structural and composition information in physics,
      chemistry, and materials science.

PMID- 29209065
TI  - Cellular automaton models for time-correlated random walks: derivation and
      analysis.
AB  - Many diffusion processes in nature and society were found to be anomalous, in the
      sense of being fundamentally different from conventional Brownian motion. An
      important example is the migration of biological cells, which exhibits non
      trivial temporal decay of velocity autocorrelation functions. This means that the
      corresponding dynamics is characterized by memory effects that slowly decay in
      time. Motivated by this we construct non-Markovian lattice-gas cellular automata
      models for moving agents with memory. For this purpose the reorientation
      probabilities are derived from velocity autocorrelation functions that are given
      a priori; in that respect our approach is "data-driven". Particular examples we
      consider are velocity correlations that decay exponentially or as power laws,
      where the latter functions generate anomalous diffusion. The computational
      efficiency of cellular automata combined with our analytical results paves the
      way to explore the relevance of memory and anomalous diffusion for the dynamics
      of interacting cell populations, like confluent cell monolayers and cell
      clustering.

PMID- 29209067
TI  - Preoperative serum thyroglobulin predicts initial distant metastasis in patients
      with differentiated thyroid cancer.
AB  - Differentiated thyroid cancer (DTC) generally has a favorable prognosis. However,
      a small percentage of patients suffer from initial distant metastasis (DM). To
      date, there is no effective predictor for the presence of initial DM. The aim of
      this study was to determine if preoperative serum thyroglobulin (Tg) level could
      predict initial DM in DTC. We reviewed an institutional thyroid cancer database
      from October 1994 to February 2016. To determine the Tg cutoff for predicting
      initial DM, 4,735 patients who were diagnosed with DTC were included in this
      study. Fifty-seven patients (1.2%) were identified as having DTC with initial DM.
      Median preoperative Tg level was 328.4 ng/ml in the initial DM group and 10.0
      ng/ml in the non-DM group. Initial DM was the most important factor affecting
      serum Tg level (beta = 2,049.32 +/- 103.40; P < 0.001). The Tg cutoff level that
      distinguished overall DM with the greatest accuracy was 63.4 ng/ml [area under
      the ROC curve 0.914, sensitivity 84.2%, specificity 90.6%, negative likelihood
      ratio (LR) 0.17, and positive LR 8.97]. Preoperative Tg levels were useful for
      predicting initial DM of DTC. Measurement of serum Tg in patients with DTC may
      guide preoperative staging evaluation and initial treatment.

PMID- 29209066
TI  - Interaction of Complement Defence Collagens C1q and Mannose-Binding Lectin with
      BMP-1/Tolloid-like Proteinases.
AB  - The defence collagens C1q and mannose-binding lectin (MBL) are immune recognition
      proteins that associate with the serine proteinases C1r/C1s and MBL-associated
      serine proteases (MASPs) to trigger activation of complement, a major innate
      immune system. Bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases
      (BTPs) are metalloproteinases with major roles in extracellular matrix assembly
      and growth factor signalling. Despite their different functions, C1r/C1s/MASPs
      and BTPs share structural similarities, including a specific CUB-EGF-CUB domain
      arrangement found only in these enzymes that mediates interactions with collagen
      like proteins, suggesting a possible functional relationship. Here we
      investigated the potential interactions between the defence collagens C1q and MBL
      and the BTPs BMP-1 and mammalian tolloid-like-1 (mTLL-1). C1q and MBL bound to
      immobilized BMP-1 and mTLL-1 with nanomolar affinities. These interactions
      involved the collagen-like regions of the defence collagens and were inhibited by
      pre-incubation of C1q or MBL with their cognate complement proteinases. Soluble
      BMP-1 and mTLL-1 did not inhibit complement activation and the defence collagens
      were neither substrates nor inhibitors of BMP-1. Finally, C1q co-localized with
      BMP-1 in skin biopsies following melanoma excision and from patients with
      recessive dystrophic epidermolysis bullosa. The observed interactions provide
      support for a functional link between complement and BTPs during inflammation and
      tissue repair.

PMID- 29209068
TI  - "Carboranyl-cysteine"-Synthesis, Structure and Self-Assembly Behavior of a Novel
      alpha-Amino Acid.
AB  - Substitution of the thiol proton in cysteine with m-carborane furnished 2-amino-3
      (1,7-dicarba-closo-dodecacarboranyl-1-thio)propanoic acid (3), a boron cluster
      amino acid that exhibits self-assembly to form micron-sized constructs. Field
      emission scanning electron microscopy revealed that ethanol solutions of 3 form
      floret-shaped constructs, while fibrillar architectures are formed in water.
      Furthermore, slow evaporation of methanol solutions of 3 produced crystals whose
      structure was revealed by X-ray crystallography. The crystal structure shows that
      the hydrogen bonding interactions between pairs of 3 result in the formation of
      bilayers of 174 A in length. The orientation of the clusters is not random in the
      crystal structure, such that the side-by-side aligned polyhedra are offset by 158
      degrees. The material was characterized by FT-IR, NMR, high resolution mass
      spectrometry and dynamic light scattering. Circular dichroism studies indicated
      that self-assembly occurs at concentrations as low as 0.01 MUM. This represents
      the first demonstration of self-assembly of a carborane-based molecule in the
      absence of metals. The amino acid motif provides opportunities for the controlled
      synthesis of extended multimeric units with tunable properties and the potential
      for applications in biology, medicine and materials chemistry.

PMID- 29209069
TI  - Transcranial direct current stimulation of the medial prefrontal cortex dampens
      mind-wandering in men.
AB  - Mind-wandering, the mind's capacity to stray from external events and generate
      task-unrelated thought, has been associated with activity in the brain default
      network. To date, little is understood about the contribution of individual nodes
      of this network to mind-wandering. Here, we investigated the role of medial
      prefrontal cortex (mPFC) in mind-wandering, by perturbing this region with
      transcranial direct current stimulation (tDCS). Young healthy participants
      performed a choice reaction time task both before and after receiving cathodal
      tDCS over mPFC, and had their thoughts periodically sampled. We found that tDCS
      over mPFC - but not occipital or sham tDCS - decreased the propensity to mind
      wander. The tDCS-induced reduction in mind-wandering occurred in men, but not in
      women, and was accompanied by a change in the content of task-unrelated though,
      which became more related to other people (as opposed to the self) following
      tDCS. These findings indicate that mPFC is crucial for mind-wandering, possibly
      by helping construction of self-relevant scenarios capable to divert attention
      inward, away from perceptual reality. Gender-related differences in tDCS-induced
      changes suggest that mPFC controls mind-wandering differently in men and women,
      which may depend on differences in the structural and functional organization of
      distributed brain networks governing mind-wandering, including mPFC.

PMID- 29209070
TI  - Assessment of Concordance between 22C3 and SP142 Immunohistochemistry Assays
      regarding PD-L1 Expression in Non-Small Cell Lung Cancer.
AB  - Different anti-PD-1 and anti-PD-L1 antibodies bind different epitopes. However,
      whether the results from the SP142 and 22C3 immunochemistry (IHC) assays can be
      interchanged to determine patient eligibility for immunotherapy remains largely
      unknown. Histologic sections from 135 tumor samples were probed with both 22C3
      and SP142 antibodies. The concordance of PD-L1 expression determined by the two
      assays was assessed. Additionally, we evaluated the association of PD-L1
      expression detected by different assays with clinicopathological features and
      prognosis. In total, 105 (77.78%) of 135 samples evaluated by the 22C3-IHC
      platform produced the same results with the SP142-IHC platform (Kappa value:
      0.481, p < 0.001). In addition, 69 (51.11%) of 135 samples evaluated by the SP142
      IHC platform produced the same results with the 22C3-IHC platform (Kappa value:
      0.324, p < 0.001). PD-L1 expression based on the 22C3-IHC assay was significantly
      correlated with smoking status, whereas that based on the SP142-IHC assay was
      correlated with smoking status, sex, and histology. Compared to the SP142-IHC
      assay, the 22C3-IHC assay usually resulted in an underestimation of PD-L1
      expression in tumor cells and immune cells. Thus, the results from the two assays
      cannot be interchanged. Our data also suggest that the use of different reagents
      may account for inconsistencies in the literature regarding the association
      between PD-L1 expression and clinicopathological features.

PMID- 29209071
TI  - Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine
      hemodynamics and induces cardiac arrhythmia in pregnant rats.
AB  - Maternal smoking with obligatory nicotine inhalation is associated with preterm
      delivery, low birth weight, fetal growth retardation and developmental defects.
      We tested the hypothesis that cigarette smoking-relevant nicotine inhalation
      during pregnancy impairs cardiovascular function and uterine hemodynamics with
      consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine
      via a novel lung alveolar region-targeted aerosol method produced nicotine
      pharmacokinetics resembling cigarette smoking in humans. This clinically relevant
      nicotine aerosol inhalation (NAI) induced transient reduction and irregular
      fluctuations in uterine artery blood flow associated with cardiac arrhythmia and
      high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia
      included sinoatrial (SA) block, sinus arrest, 2 degrees  and 3 degrees 
      atrioventricular (A-V) block and supraventricular escape rhythm. These effects
      were blocked by the nicotinic acetylcholine receptor (nAChR) antagonist
      mecamylamine. Resection of the ovarian nerve, which innervates uterine blood
      vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest
      that the rapid rise pattern of arterial blood nicotine concentration stimulates
      and then desensitizes autonomic nAChRs leading to disruptions of cardiac function
      as well as systemic and uterine hemodynamics that reduces uteroplacental blood
      flow, a mechanism underlying maternal smoking-associated pregnancy complications
      and developmental disorders. These findings challenge the safety of pure nicotine
      inhalation, i.e., E-cigarettes.

PMID- 29209072
TI  - Free SepF interferes with recruitment of late cell division proteins.
AB  - The conserved cell division protein SepF aligns polymers of FtsZ, the key cell
      division protein in bacteria, during synthesis of the (Fts)Z-ring at midcell, the
      first stage in cytokinesis. In addition, SepF acts as a membrane anchor for the Z
      ring. Recently, it was shown that SepF overexpression in Mycobacterium smegmatis
      blocks cell division. Why this is the case is not known. Surprisingly, we found
      in Bacillus subtilis that SepF overproduction does not interfere with Z-ring
      assembly, but instead blocks assembly of late division proteins responsible for
      septum synthesis. Transposon mutagenesis suggested that SepF overproduction
      suppresses the essential WalRK two-component system, which stimulates expression
      of ftsZ. Indeed, it emerged that SepF overproduction impairs normal WalK
      localization. However, transcriptome analysis showed that the WalRK activity was
      in fact not reduced in SepF overexpressing cells. Further experiments indicated
      that SepF competes with EzrA and FtsA for binding to FtsZ, and that binding of
      extra SepF by FtsZ alleviates the cell division defect. This may explain why
      activation of WalRK in the transposon mutant, which increases ftsZ expression,
      counteracts the division defect. In conclusion, our data shows that an imbalance
      in early cell division proteins can interfere with recruitment of late cell
      division proteins.

PMID- 29209073
TI  - Integrating Clinical and Multiple Omics Data for Prognostic Assessment across
      Human Cancers.
AB  - Multiple omic profiles have been generated for many cancer types; however,
      comprehensive assessment of their prognostic values across cancers is limited. We
      conducted a pan-cancer prognostic assessment and presented a multi-omic kernel
      machine learning method to systematically quantify the prognostic values of high
      throughput genomic, epigenomic, and transcriptomic profiles individually,
      integratively, and in combination with clinical factors for 3,382 samples across
      14 cancer types. We found that the prognostic performance varied substantially
      across cancer types. mRNA and miRNA expression profile frequently performed the
      best, followed by DNA methylation profile. Germline susceptibility variants
      displayed low prognostic performance consistently across cancer types. The
      integration of omic profiles with clinical variables can lead to substantially
      improved prognostic performance over the use of clinical variables alone in half
      of cancer types examined. Moreover, we showed that the kernel machine learning
      method consistently outperformed existing prognostic signatures, suggesting that
      including a large number of omic biomarkers may provide substantial improvement
      in prognostic assessment. Our study provides a comprehensive portrait of omic
      architecture for tumor prognosis across cancers, and highlights the prognostic
      value of genome-wide omic biomarker aggregation, which may facilitate refined
      prognostic assessment in the era of precision oncology.

PMID- 29209074
TI  - In vitro and in vivo antifungal activities and mechanism of heteropolytungstates
      against Candida species.
AB  - The antifungal activities of heteropolytungstates, alpha-1,2,3-K6H[SiW9V3O40]
      (SiW-3), K13[Ce(SiW11O39)2].17H2O (SiW-5), K13[Eu(SiW11O39)2].25H2O (SiW-10),
      K6PV3W9O40 (PW-6), alpha-K4PVW11O40 (PW-8), were screened in 29 Candida albicans,
      8 Candida glabrata, 3 Candida krusei, 2 Candida parapsilosis, 1 Candida
      tropicalis, and 1 Cryptococcus neoformans strains using the CLSI M27-A3 method.
      SiW-5 had the highest efficacy with a minimum inhibitory concentration (MIC)
      values of <0.2-10.2 MUM in vitro. The antifungal mechanism, acute toxicity and in
      vivo antifungal activity of SiW-5 were then evaluated in C. albicans. The results
      showed that SiW-5 damaged the fungal cell membrane, reduce the ergosterol content
      and its main mode of action was through inhibition of ergosterol biosynthesis.
      Real-time PCR showed that ERG1, ERG7, ERG11 and ERG28 were all significantly
      upregulated by SiW-5. An acute toxicity study showed the 50% lethal dose (LD50)
      of SiW-5 for ICR mice was 1651.5 mg/kg. And in vivo antifungal studies
      demonstrated that SiW-5 reduced both the morbidity and fungal burden of mice
      infected with C. albicans. This study demonstrates that SiW-5 is a potential
      antifungal candidate against the Candida species.

PMID- 29209079
TI  - Zero-calorie sugar delivery to roots.

PMID- 29209080
TI  - Strategies for survival.

PMID- 29209082
TI  - How to get old without aging.

PMID- 29209081
TI  - Low number of fixed somatic mutations in a long-lived oak tree.
AB  - Because plants do not possess a defined germline, deleterious somatic mutations
      can be passed to gametes, and a large number of cell divisions separating zygote
      from gamete formation may lead to many mutations in long-lived plants. We
      sequenced the genome of two terminal branches of a 234-year-old oak tree and
      found several fixed somatic single-nucleotide variants whose sequential
      appearance in the tree could be traced along nested sectors of younger branches.
      Our data suggest that stem cells of shoot meristems in trees are robustly
      protected from the accumulation of mutations.

PMID- 29209083
TI  - Maintenance of carbohydrate transport in tall trees.
AB  - Trees present a critical challenge to long-distance transport because as a tree
      grows in height and the transport pathway increases in length, the hydraulic
      resistance of the vascular tissue should increase. This has led many to question
      whether trees can rely on a passive transport mechanism to move carbohydrates
      from their leaves to their roots. Although species that actively load sugars into
      their phloem, such as vines and herbs, can increase the driving force for
      transport as they elongate, it is possible that many trees cannot generate high
      turgor pressures because they do not use transporters to load sugar into the
      phloem. Here, we examine how trees can maintain efficient carbohydrate transport
      as they grow taller by analysing sieve tube anatomy, including sieve plate
      geometry, using recently developed preparation and imaging techniques, and by
      measuring the turgor pressures in the leaves of a tall tree in situ. Across nine
      deciduous species, we find that hydraulic resistance in the phloem scales
      inversely with plant height because of a shift in sieve element structure along
      the length of individual trees. This scaling relationship seems robust across
      multiple species despite large differences in plate anatomy. The importance of
      this scaling becomes clear when phloem transport is modelled using turgor
      pressures measured in the leaves of a mature red oak tree. These pressures are of
      sufficient magnitude to drive phloem transport only in concert with structural
      changes in the phloem that reduce transport resistance. As a result, the key to
      the long-standing mystery of how trees maintain phloem transport as they increase
      in size lies in the structure of the phloem and its ability to change hydraulic
      properties with plant height.

PMID- 29209084
TI  - Sublethal effects of buprofezin on development and reproduction in the white
      backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae).
AB  - In the present study, the effects of sublethal concentrations of buprofezin on
      life-table traits of S. furcifera were evaluated for two consecutive generations
      (F0 and F1). Our results exhibited that the fecundity, life span (longevity) and
      hatchability of the F0 and F1 generations were significantly decreased at LC30
      compared to the control. However, copulation was not significantly affected for
      the F0 or F1 generations at sublethal concentrations. The female life span was
      affected negatively at both treatments in F0 and at LC30 in F1, compared to the
      control. Furthermore, significant effects of the sublethal concentrations were
      found on the developmental rate of all instars except the 3rd instar of F1.
      However, the pre-adult period, total pre-oviposition period (TPOP) and adult pre
      oviposition period (APOP) significantly increased in F1 individuals at LC30 and
      LC10 compared to the control. Our findings revealed that demographic characters
      (survival rate, intrinsic rate of increase (ri), finite rate of increase
      (lambda), net reproductive rate (R 0), and gross reproductive rate (GRR)) of the
      F1 generation (from F0 parents) significantly decreased compared to the untreated
      group; however, the generation time (T) increased at LC10. Therefore, the results
      suggested that buprofezin could adversely affect individuals in the successive
      generation.

PMID- 29209085
TI  - Integrated Genomic and Proteomic Analyses of High-level Chloramphenicol
      Resistance in Campylobacter jejuni.
AB  - Campylobacter jejuni is a major zoonotic pathogen, and its resistance to
      antibiotics is of great concern for public health. However, few studies have
      investigated the global changes of the entire organism with respect to antibiotic
      resistance. Here, we provide mechanistic insights into high-level resistance to
      chloramphenicol in C. jejuni, using integrated genomic and proteomic analyses. We
      identified 27 single nucleotide polymorphisms (SNPs) as well as an efflux pump
      cmeB mutation that conferred modest resistance. We determined two radical S
      adenosylmethionine (SAM) enzymes, one each from an SNP gene and a differentially
      expressed protein. Validation of major metabolic pathways demonstrated
      alterations in oxidative phosphorylation and ABC transporters, suggesting energy
      accumulation and increase in methionine import. Collectively, our data revealed a
      novel rRNA methylation mechanism by a radical SAM superfamily enzyme, indicating
      that two resistance mechanisms existed in Campylobacter. This work provided a
      systems biology perspective on understanding the antibiotic resistance mechanisms
      in bacteria.

PMID- 29209086
TI  - Long noncoding RNAs that respond to Fusarium oxysporum infection in 'Cavendish'
      banana (Musa acuminata).
AB  - Long noncoding RNAs (lncRNAs) are a class of genes that influence a variety of
      biological functions through acting as signal, decoy, guide, and scaffold
      molecules. In banana (Musa spp.), an important economic fruit crop, particularly
      in Southeast Asia, the wilt disease caused by Fusarium oxysporum f. sp. cubense
      (Foc), especially strain Foc TR4, is disastrous. In banana, how the biogenesis of
      these lncRNAs is regulated in response to pathogen infection is still largely
      unknown. In this study, strand-specific paired-end RNA sequencing of banana
      samples was performed on susceptible and resistant cultivars inoculated with Foc,
      with three biological replicates and at two different times after infection.
      Overall, 5,294 lncRNAs were predicted with high confidence through strict
      filtration, including long intergenic ncRNA (lincRNA) and antisense lncRNA.
      Differentially expressed (DE) lncRNAs were identified in response to Foc
      infection in the inoculated versus the mock-inoculated banana of the susceptible
      'BX' and resistant 'NK' cultivars. Through KEGG, GO, and the expression levels of
      the DE lncRNAs, some DE lncRNAs were predicted to be involved in plant-pathogen
      interactions and phytohormone signal transduction. In this study, this catalog of
      lncRNAs and their properties will facilitate further experimental studies and
      functional classifications of these genes.

PMID- 29209087
TI  - Quantitative trait loci mapping for feed conversion efficiency in crucian carp
      (Carassius auratus).
AB  - QTL is a chromosomal region including single gene or gene clusters that determine
      a quantitative trait. While feed efficiency is highly important in aquaculture
      fish, little genetic and genomic progresses have been made for this trait. In
      this study, we constructed a high-resolution genetic linkage map in a full-sib F1
      family of crucian carp (Carassius auratus) consisting of 113 progenies with 8,460
      SNP markers assigning onto 50 linkage groups (LGs). This genetic map spanned
      4,047.824 cM (0.478 cM/marker) and covered 98.76% of the crucian carp genome. 35
      chromosome-wide QTL affecting feed conversion efficiency (FCE, 8 QTL), relative
      growth rate (RGR, 9 QTL), average daily gain (ADG, 13 QTL) and average daily feed
      intake (ADFI, 5 QTL) were detected on 14 LGs, explaining 14.0-20.9% of the
      phenotypic variations. In LGs of LG16, LG25, LG36 and LG49, several QTL affecting
      different traits clustered together at the identical or close regions of the same
      linkage group. Seven candidate genes, whose biological functions may involve in
      the energy metabolism, digestion, biosynthesis and signal transduction, were
      identified from these QTL intervals by comparative genomics analysis. These
      results provide a basis for elucidating genetic mechanism of feed efficiency and
      potential marker-assisted selection in crucian carp.

PMID- 29209089
TI  - MRD in multiple myeloma: more questions than answers?

PMID- 29209088
TI  - Inhibitory effects of curcumin and cyclocurcumin in 1-methyl-4-phenylpyridinium
      (MPP+) induced neurotoxicity in differentiated PC12 cells.
AB  - Development and progression of neurodegenerative diseases like Parkinson's
      disease (PD) involve multiple pathways. Thus, effective therapeutic treatments
      should intervene to address all these pathways simultaneously for greater
      success. Most of the current pharmacotherapeutic approaches just supplement
      striatal dopamine. Hence, natural extracts of plants with therapeutic potential
      have been explored. Curcuminoids belong to one such group of polyphenol which
      show immense therapeutic effects. Here, we have used intracellular reactive
      oxygen species (ROS) measurement, and two-photon fluorescence lifetime imaging
      microscopy (2P-FLIM) of cellular autofluorescent co-enzyme reduced nicotinamide
      adenine dinucleotide (NADH) to study the inhibitory effects of curcumin and
      cyclocurcumin in alleviating PD like neurotoxicity of 1-methyl-4-phenylpyridinium
      (MPP+) in neuronal growth factor (NGF) induced differentiated PC12 cells. Our
      results showed that both cyclocurcumin and curcumin reduced the level of ROS
      caused by MPP+ treatment. Moreover, a significant increase in the free, protein
      bound, and average NADH fluorescence lifetimes along with a decrease in the
      relative contribution of free- vs. protein-bound NADH components in curcuminoids
      treated cells (pretreated with MPP+) were observed compared with those treated
      with MPP+ only. This study, which indicates that cyclocurcumin offers higher
      neuronal protection than curcumin, may initiate further studies of these
      compounds in the cure of neurodegenerative diseases.

PMID- 29209090
TI  - Meta-analysis of gut microbiome studies identifies disease-specific and shared
      responses.
AB  - Hundreds of clinical studies have demonstrated associations between the human
      microbiome and disease, yet fundamental questions remain on how we can generalize
      this knowledge. Results from individual studies can be inconsistent, and
      comparing published data is further complicated by a lack of standard processing
      and analysis methods. Here we introduce the MicrobiomeHD database, which includes
      28 published case-control gut microbiome studies spanning ten diseases. We
      perform a cross-disease meta-analysis of these studies using standardized
      methods. We find consistent patterns characterizing disease-associated microbiome
      changes. Some diseases are associated with over 50 genera, while most show only
      10-15 genus-level changes. Some diseases are marked by the presence of
      potentially pathogenic microbes, whereas others are characterized by a depletion
      of health-associated bacteria. Furthermore, we show that about half of genera
      associated with individual studies are bacteria that respond to more than one
      disease. Thus, many associations found in case-control studies are likely not
      disease-specific but rather part of a non-specific, shared response to health and
      disease.

PMID- 29209092
TI  - Opposite effects of dissolved oxygen on the removal of As(III) and As(V) by
      carbonate structural Fe(II).
AB  - Freshly prepared carbonate structural Fe(II) (CSF) was used to immobilize As(III)
      and As(V) in wastewater under oxic and anoxic conditions. Dissolved oxygen was
      found to exert opposite effects on these two arsenic species. The sorption
      density of As(III) was higher under oxic conditions, whereas that of As(V) was
      higher under anoxic conditions. X-ray diffraction and infrared spectroscopic
      analyses indicated that crystalline parasymplesite (Fe(II)3(AsO4)2.8H2O) was
      formed when As(V) was removed under anoxic conditions, while an amorphous Fe-As
      containing precipitate was formed when As(III) was removed under oxic conditions.
      The distribution of arsenic and iron between the solution and sediments suggested
      that the oxidation of structural Fe(II) promoted coprecipitation process and
      inhibited surface complexation. X-ray photoelectron spectroscopic analyses
      revealed that more As(III) was oxidized under oxic condition, which contributed
      to a higher sorption capacity for As(III). The formation of parasymplesite
      through surface complexation/precipitation was proposed to be more effective for
      the removal of As(V) by CSF, while As(III) was more efficiently removed through
      coprecipitation. Together, the results suggest that CSF may be an effective
      material for sequestering both As(III) and As(V). In addition, attention should
      be paid to the dissolved oxygen content when remediating different arsenic
      species.

PMID- 29209091
TI  - Type I interferons drive inflammasome-independent emergency monocytopoiesis
      during endotoxemia.
AB  - Emergency monocytopoiesis is an inflammation-driven hematological process that
      supplies the periphery with monocytes and subsequently with macrophages and
      monocyte-derived dendritic cells. Yet, the regulatory mechanisms by which early
      bone marrow myeloid progenitors commit to monocyte-derived phagocytes during
      endotoxemia remains elusive. Herein, we show that type I interferons signaling
      promotes the differentiation of monocyte-derived phagocytes at the level of their
      progenitors during a mouse model of endotoxemia. In this model, we characterized
      early changes in the numbers of conventional dendritic cells, monocyte-derived
      antigen-presenting cells and their respective precursors. While loss of caspase
      1/11 failed to impair a shift toward monocytopoiesis, we observed sustained type
      I-IFN-dependent monocyte progenitors differentiation in the bone marrow
      correlated to an accumulation of Mo-APCs in the spleen. Importantly, IFN-alpha
      and -beta were found to efficiently generate the development of monocyte-derived
      antigen-presenting cells while having no impact on the precursor activity of
      conventional dendritic cells. Consistently, the LPS-driven decrease of
      conventional dendritic cells and their direct precursor occurred independently of
      type-I-IFN signaling in vivo. Our characterization of early changes in
      mononuclear phagocytes and their dependency on type I IFN signaling during sepsis
      opens the way to the development of treatments for limiting the immunosuppressive
      state associated with sepsis.

PMID- 29209093
TI  - Preparation and thermal properties of mineral-supported polyethylene glycol as
      form-stable composite phase change materials (CPCMs) used in asphalt pavements.
AB  - Three kinds of mineral-supported polyethylene glycol (PEG) as form-stable
      composite phase change materials (CPCMs) were prepared to choose the most
      suitable CPCMs in asphalt pavements for the problems of asphalt pavements rutting
      diseases and urban heat islands. The microstructure and chemical structure of
      CPCMs were characterized by SEM, FT-IR and XRD. Thermal properties of the CPCMs
      were determined by TG and DSC. The maximum PEG absorption of diatomite (DI),
      expanded perlite (EP) and expanded vermiculite (EVM) could reach 72%, 67% and
      73.6%, respectively. The melting temperatures and latent heat of CPCMs are in the
      range of 52-55  degrees C and 100-115 J/g, respectively. The results show that
      PEG/EP has the best thermal and chemical stability after 100 times of heating
      cooling process. Moreover, crystallization fraction results show that PEG/EP has
      slightly higher latent heats than that of PEG/DI and PEG/EVM. Temperature
      adjusting asphalt mixture was prepared by substituting the fine aggregates with
      PEG/EP CPCMs. The upper surface maximum temperature difference of temperature
      adjusting asphalt mixture reaches about 7.0  degrees C in laboratory, and the
      surface peak temperature reduces up to 4.3  degrees C in the field experiment
      during a typical summer day, indicating a great potential application for
      regulating pavement temperature field and alleviating the urban heat islands.

PMID- 29209094
TI  - Possible function of the second RecJ-like protein in stalled replication fork
      repair by interacting with Hef.
AB  - RecJ was originally identified in Escherichia coli and plays an important role in
      the DNA repair and recombination pathways. Thermococcus kodakarensis, a
      hyperthermophilic archaeon, has two RecJ-like nucleases. These proteins are
      designated as GAN (GINS-associated nuclease) and HAN (Hef-associated nuclease),
      based on the protein they interact with. GAN is probably a counterpart of Cdc45
      in the eukaryotic CMG replicative helicase complex. HAN is considered mainly to
      function with Hef for restoration of the stalled replication fork. In this study,
      we characterized HAN to clarify its functions in Thermococcus cells. HAN showed
      single-strand specific 3' to 5' exonuclease activity, which was stimulated in the
      presence of Hef. A gene disruption analysis revealed that HAN was non-essential
      for viability, but the DeltaganDeltahan double mutant did not grow under optimal
      conditions at 85  degrees C. This deficiency was not fully recovered by
      introducing the mutant han gene, encoding the nuclease-deficient HAN protein,
      back into the genome. These results suggest that the unstable replicative
      helicase complex without GAN performs ineffective fork progression, and thus the
      stalled fork repair system including HAN becomes more important. The nuclease
      activity of HAN is required for the function of this protein in T. kodakarensis.

PMID- 29209095
TI  - Life role salience and subjective well-being among Macedonian employees: Does
      family-supportive organization perception moderate this relationship.
AB  - OBJECTIVES: As many studies have shown, one of the most important tendencies of
      employees nowadays is to achieve work- life balance. Organizations should develop
      various activities and create supportive climate, within the framework of which
      employees will have opportunities to realize aforementioned goals which in turn
      would increase work productivity and work motivation. The aim of this paper was
      to examine how subjective well-being (life satisfaction and exhaustion) is
      associated with commitment to work and family roles under the conditions of
      strongly and weakly perceived organizational support for family life among health
      care professionals, teachers and bankers in Macedonia. Marriage duration and the
      number of children were introduced as control variables. MATERIAL AND METHODS:
      This cross-sectional study was conducted on a sample of 198 full-time employed
      doctors, nurses, teachers and bankers. Research variables were assessed using
      self-reported measures/ questionnaires. Hierarchical multiple linear regression
      was performed for data analysis. RESULTS: It was revealed that occupational role
      commitment contributed to highly expressed life satisfaction, while exhaustion
      was predicted by marital role commitment. These relationships were stronger among
      surveyed employees who reported positive family-supportive organization
      perception, but tested moderation effect of this variable was not statistically
      significant. Findings demonstrated that family-supportive organization perception
      moderated association of the number of children with life satisfaction, that is,
      participants who perceived an organization as family-supportive and had more
      children were more satisfied with their life in general. CONCLUSIONS: Results
      highlighted the importance of organizational orientation toward employees, their
      commitment to work and family roles, and their subjective well-being, as
      characteristics that might contribute to higher work engagement, success and
      family satisfaction. Int J Occup Med Environ Health 2018;31(3):281-291.

PMID- 29209096
TI  - Letter to the Editor (July 26, 2017) concerning the paper "Impact of
      electromagnetic radiation emitted by monitors on changes in the cellular membrane
      structure and protective antioxidant effect of vitamin A - In vitro study".

PMID- 29209097
TI  - Authors' response (September 1, 2017) to the letter to the Editor concerning the
      paper "Impact of electromagnetic radiation emitted by monitors on changes in the
      cellular membrane structure and protective antioxidant effect of vitamin A - In
      vitro study".

PMID- 29209098
TI  - The Distribution Frequency of Interferon-Gamma Receptor 1 Gene Polymorphisms in
      Interferon-gamma Release Assay-Positive Patients.
AB  - Tuberculosis is caused by mycobacterium, a potentially fatal infectious
      bacterium. In recent years, TB cases increased in the whole world. WHO statistics
      data shows that the world's annual tuberculosis incidence was 8~10 million with
      about 3 million deaths. Several studies have shown that susceptibility to
      tuberculosis may be associated with IFNGR1 gene polymorphisms. Here, we report
      the distribution frequency of IFNGR1 gene polymorphisms in 103 cases of IGA
      negative patients and 100 cases of IGA-positive patients from China by sequencing
      the IFNGR1 proximal ~750 bp promoter region. We found a total of 5 types of site
      mutations: -611 (G/A), -56 (T/C), -255 (C/T), -359 (T/C), and -72 (C/T). The two
      main types of gene polymorphisms among the IGA-negative and IGA-positive groups
      were -611 (G/A), with mutation rates of 88.3% and 78.4%, respectively, and -56
      (T/C), with mutation rates of 84.5% and 83.8%, respectively, which had no
      statistical significance, and there was no correlation with the incidence of
      tuberculosis.

PMID- 29209100
TI  - Corrigendum to "RANTES Gene Polymorphisms Associated with HIV-1 Infections in
      Kenyan Population".
AB  - [This corrects the article DOI: 10.1155/2016/4703854.].

PMID- 29209099
TI  - Polymorphisms in CCR5Delta32 and Risk of HIV-1 Infection in the Southeast of
      Caspian Sea, Iran.
AB  - Prevalence of CCR5Delta32 among blood samples of more than 400 healthy and HIV-1
      infected people was investigated in Iran. Polymerase chain reaction (PCR)
      following DNA extraction was used. Desired frequency was analyzed by Hardy
      Weinberg equilibrium (HWE) analysis and SPSS 16.0 software to harvest the
      results. The prevalence of CCRDelta32 heterozygote genotype was 3% in healthy
      people and 0.7% in HIV-1-infected individuals. There was no homozygote
      CCR5Delta32 in both groups, and the allele Delta32 was only observed in 1.5% and
      0.36% of healthy and HIV-1-infected participants, respectively. Therefore
      according to this study, the frequency of the allele CCR5Delta32 indicates no
      significant difference between either groups (p = 0.18) and it sounds that the
      mentioned mutation in heterozygote people would not affect their susceptibility
      against HIV infection. Genotyping trial in Iranians with HIV infection is
      supposed to be helpful as a matter of prognostic purposes.

PMID- 29209101
TI  - Role of Microvessels in Oxygen Supply to Tissue.
AB  - Since the early work of August Krogh in 1919, capillaries have been assumed to be
      the sole supplier of oxygen for tissue. Recent studies provide convincing
      evidence that other microvessels also contribute to tissue oxygenation and that
      capillaries play a much more complex role than originally proposed by Krogh.

PMID- 29209102
TI  - The Incidence of Depression among the Population of Central Kazakhstan and Its
      Relationship with Sociodemographic Characteristics.
AB  - It has been established that the presence of depression is accompanied by an
      increased risk of morbidity and mortality in cerebrovascular and cardiovascular
      diseases and diabetes. The aim of this research was to estimate depressive
      symptom prevalence among the population in Central Kazakhstan and to define the
      relationship with social-demographic and behavioral factors. 1820 respondents of
      the population of Central Kazakhstan, aged 25 to 65, were performed. Participants
      included 777 urban and 1043 rural residents. Depressive symptoms assessed with
      the Patient Health Questionnaire (PHQ-9). The results showed that some degree of
      depressive symptoms was detected in 75.7% of the respondents. A minimal degree of
      depressive symptoms was observed in 28.51%, mild in 27.7%, moderate in 13.7%, and
      severe and very severe degree of depressive symptoms in 4.6% and 1.2%,
      respectively; the absence of depression symptoms was reported in 24.3% of the
      respondents. The study found a relationship between the prevalence of depressive
      symptoms and factors such as gender, education, income, presence of chronic
      diseases, and physical activity. We have not found a correlation between the
      frequencies of depressive symptoms with age, employment, character of labor, and
      marital status.

PMID- 29209104
TI  - T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6
      Receptor Blocker Therapy.
AB  - Data on the impact of biological therapies on the T-cell phenotype in rheumatoid
      arthritis are limited. Here, we prospectively measured the percentages of 15
      circulating T-cell subtypes using flow cytometry. We obtained transversal and
      longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders,
      and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after
      biological therapy. Untreated RA patients and healthy controls were also
      included. The important findings are the following: (1) the proportion of
      regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes
      normal in all long-term-treated groups; (2) in anti-TNF responders as well as in
      nonresponders, the frequencies of naive CD4+ and CD8+ cells are lower, whereas
      those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are
      higher than those in untreated RA or healthy controls; (3) in IL-6R responders,
      Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared
      to that in anti-TNF-treated patients and controls; (4) pending confirmation, a
      CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic
      response to anti-TNF therapy. This study provides comprehensive information
      regarding the long-term impacts of those biological therapies on the ecotaxis of
      T-cells in RA. The ClinicalTrials.gov registration number of our study is
      NCT03266822.

PMID- 29209105
TI  - Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and
      Prostaglandin E2 from Rat Trigeminal Ganglia.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat
      migraine, but the mechanisms of their effects in this pathology are not fully
      elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP)
      have been implicated in the pathophysiology of migraine. The release of CGRP and
      prostaglandin E2 (PGE2) from freshly isolated rat trigeminal ganglia was
      evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen,
      NSAIDs with different pharmacological features. Thirty minutes after oral
      administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an
      inflammatory soup, while the other NSAIDs were ineffective at this point in time.
      Two hours after oral nimesulide (5 and 10 mg/Kg) and ketoprofen (10 mg/Kg), but
      not of etoricoxib, a significant decrease in the CGRP release was observed. All
      drugs reduced PGE2, although with some differences in timing and doses, and the
      action on CGRP does not seem to be related to PGE2 inhibition. The reduction of
      CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help
      to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes
      only nimesulide was effective in reducing CGRP release, these results suggest
      that this NSAID may exert a particularly rapid effect in patients with migraine.

PMID- 29209106
TI  - Noncoding RNAs as drivers of the phenotypic plasticity of oesophageal mucosa.
AB  - The histological commitment of the lower oesophageal mucosa largely depends on a
      complex molecular landscape. After extended inflammatory insult due to
      gastroesophageal reflux disease, squamous oesophageal mucosa may differentiate
      into columnar metaplastic mucosa. In this setting, the presence of intestinal
      metaplasia is considered the starting point of Barrett's carcinogenetic cascade.
      Aside from secondary prevention strategies for Barrett's mucosa (BM) patients,
      there are multiple endoscopic ablative therapies available for BM eradication and
      for the replacement of metaplastic epithelia with a neosquamous mucosa. However,
      BM frequently recurs in a few years, which supports the notable phenotypic
      plasticity of the oesophageal mucosa. In recent years, several reports pinpointed
      a class of small noncoding RNAs, the microRNAs (miRNAs), as principal effectors
      and regulators of oesophageal mucosa metaplastic (and neoplastic) transformation.
      Because of miRNAs notable stability in fixed archival diagnostic specimens,
      expression profiling of miRNAs represent an innovative diagnostic, prognostic and
      predictive tool in the stratification of phenotypic alterations in the
      oesophageal mucosa.

PMID- 29209103
TI  - HIV as a Cause of Immune Activation and Immunosenescence.
AB  - Systemic immune activation has emerged as an essential component of the
      immunopathogenesis of HIV. It not only leads to faster disease progression, but
      also to accelerated decline of overall immune competence. HIV-associated immune
      activation is characterized by an increase in proinflammatory mediators,
      dysfunctional T regulatory cells, and a pattern of T-cell-senescent phenotypes
      similar to those seen in the elderly. These changes predispose HIV-infected
      persons to comorbid conditions that have been linked to immunosenescence and
      inflamm-ageing, such as atherosclerosis and cardiovascular disease,
      neurodegeneration, and cancer. In the antiretroviral treatment era, development
      of such non-AIDS-defining, age-related comorbidities is a major cause of
      morbidity and mortality. Treatment strategies aimed at curtailing persistent
      immune activation and inflammation may help prevent the development of these
      conditions. At present, the most effective strategy appears to be early
      antiretroviral treatment initiation. No other treatment interventions have been
      found effective in large-scale clinical trials, and no adjunctive treatment is
      currently recommended in international HIV treatment guidelines. This article
      reviews the role of systemic immune activation in the immunopathogenesis of HIV
      infection, its causes and the clinical implications linked to immunosenescence in
      adults, and the therapeutic interventions that have been investigated.

PMID- 29209107
TI  - Functional interaction of endoplasmic reticulum stress and hepatitis B virus in
      the pathogenesis of liver diseases.
AB  - Hepatitis B virus (HBV) is a non-cytopathic virus that causes acute and chronic
      inflammatory liver diseases, often leading to the pathogenesis of hepatocellular
      carcinoma (HCC). Although many studies for the roles of HBV on pathogenesis of
      the liver diseases, such as non-alcoholic fatty liver disease (NAFLD), hepatic
      inflammation, cirrhosis, and HCC, have been reported, the mechanisms are not
      fully understood. Endoplasmic reticulum (ER) and mitochondria have the protective
      mechanisms to restore their damaged function by intrinsic or extrinsic stresses,
      but their chronic dysfunctions are associated with the pathogenesis of the
      various diseases. Furthermore, HBV can affect intra- or extracellular homeostasis
      through induction of ER and mitochondrial dysfunctions, leading to liver injury.
      Therefore, the mechanism by which HBV induces ER or mitochondrial stresses may be
      a therapeutic target for treatment of liver diseases.

PMID- 29209108
TI  - Pathological process of liver sinusoidal endothelial cells in liver diseases.
AB  - Cirrhosis develops from liver fibrosis and is the severe pathological stage of
      all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C
      virus infection is especially common. Liver fibrosis and cirrhosis involve excess
      production of extracellular matrix, which is closely related to liver sinusoidal
      endothelial cells (LSECs). Damaged LSECs can synthesize transforming growth
      factor-beta and platelet-derived growth factor, which activate hepatic stellate
      cells and facilitate the synthesis of extracellular matrix. Herein, we highlight
      the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at
      different stages and focus on the formation and development of liver fibrosis and
      cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are
      described in detail. Targeting LSECs has high therapeutic potential for liver
      diseases. Further understanding of the mechanism of action will provide stronger
      evidence for the development of anti-LSEC drugs and new directions for diagnosis
      and treatment of liver diseases.

PMID- 29209109
TI  - Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated
      and cholestatic rats.
AB  - AIM: To investigate the effect of resveratrol on biliary secretion of cholephilic
      compounds in healthy and bile duct-obstructed rats. METHODS: Resveratrol (RSV) or
      saline were administered to rats by daily oral gavage for 28 d after sham
      operation or reversible bile duct obstruction (BDO). Bile was collected 24 h
      after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate
      azithromycin. Bile acids, glutathione and azithromycin were measured in bile to
      quantify their level of biliary secretion. Liver expression of enzymes and
      transporters relevant for bile production and biliary secretion of major bile
      constituents and drugs were analyzed at the mRNA and protein levels using qRT-PCR
      and Western blot analysis, respectively. The TR-FRET PXR Competitive Binding
      Assay kit was used to determine the agonism of RSV at the pregnane X receptor.
      RESULTS: RSV increased bile flow in sham-operated rats due to increased biliary
      secretion of bile acids (BA) and glutathione. This effect was accompanied by the
      induction of the hepatic rate-limiting transporters for bile acids and
      glutathione, Bsep and Mrp2, respectively. RSV also induced Cyp7a1, an enzyme that
      is crucial for bile acid synthesis; Mrp4, a transporter important for BA
      secretion from hepatocytes to blood; and Mdr1, the major apical transporter for
      xenobiotics. The findings were supported by increased biliary secretion of
      azithromycin. The TR-FRET PXR competitive binding assay confirmed RSV as a weak
      agonist of the human nuclear receptor PXR, which is a transcriptional regulator
      of Mdr1/Mrp2. RSV demonstrated significant hepatoprotective properties against
      BDO-induced cirrhosis. RSV also reduced bile flow in BDO rats without any
      corresponding change in the levels of the transporters and enzymes involved in
      RSV-mediated hepatoprotection. CONCLUSION: Resveratrol administration for 28 d
      has a distinct effect on bile flow and biliary secretion of cholephilic compounds
      in healthy and bile duct-obstructed rats.

PMID- 29209110
TI  - Chitinase 3-like 1 secreted by peritumoral macrophages in esophageal squamous
      cell carcinoma is a favorable prognostic factor for survival.
AB  - AIM: To identify whether chitinase 3-like 1 (CHI3L1) serves as a suitable
      biomarker for the prognosis of esophageal squamous cell carcinoma (ESCC) and to
      analyze this protein's cellular source. METHODS: An ELISA was conducted to detect
      the concentration of CHI3L1 in the serum of 150 ESCC patients diagnosed between
      January 2001 and February 2005. The prognostic relevance of CHI3L1 was evaluated
      by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was
      reanalyzed, and fluorescent staining was utilized to explore the cellular origins
      of CHI3L1. We stimulated monocyte-derived macrophages (MDMs) with either IL-6 or
      the supernatant of the ESCC cell line Eca-109 and later investigated the level of
      CHI3L1 by qPCR and ELISA. RESULTS: The level of serum CHI3L1 was higher in older
      patients (>= 60) than in patients under the age of 60 (P = 0.001). The patients
      with higher levels of CHI3L1 had a significantly shorter overall survival,
      whereas the traditional markers, carcinoembryonic antigen and squamous cell
      carcinoma antigen, were less effective (P > 0.05). A multivariate Cox analysis (P
      = 0.001) indicated that CHI3L1 was an independent prognostic factor for ESCC
      patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3L1.
      Interleukin-6 (IL-6) and the supernatant of Eca-109 containing IL-6 stimulated
      MDMs to secrete CHI3L1. The serum concentration of CHI3L1 in the ESCC patients
      showed a weak correlation with the laboratory inflammatory parameters neutrophil
      (NEU, P = 0.045), neutrophil/lymphocyte rate (NLR, P = 0.016), and C-reactive
      protein (CRP, P < 0.001). CONCLUSION: Our study first established a connection
      between the pretreated CHI3L1 and patients with ESCC, and the serum CHI3L1 was
      primarily secreted by ESCC-surrounded macrophages.

PMID- 29209111
TI  - Palmitate induces fat accumulation by activating C/EBPbeta-mediated G0S2
      expression in HepG2 cells.
AB  - AIM: To determine the role of G0/G1 switch gene 2 (G0S2) and its transcriptional
      regulation in palmitate-induced hepatic lipid accumulation. METHODS: HepG2 cells
      were treated with palmitate, or palmitate in combination with CCAAT/enhancer
      binding protein (C/EBP)beta siRNA or G0S2 siRNA. The mRNA expression of
      C/EBPbeta, peroxisome proliferator-activated receptor (PPAR)gamma and PPARgamma
      target genes (G0S2, GPR81, GPR109A and Adipoq) was examined by qPCR. The protein
      expression of C/EBPbeta, PPARgamma, and G0S2 was determined by Western blotting.
      Lipid accumulation was detected with Oil Red O staining and quantified by
      absorbance value of the extracted Oil Red O dye. Lipolysis was evaluated by
      measuring the amount of glycerol released into the medium. RESULTS: Palmitate
      caused a dose-dependent increase in lipid accumulation and a dose-dependent
      decrease in lipolysis in HepG2 cells. In addition, palmitate increased the mRNA
      expression of C/EBPbeta, PPARgamma, and PPARgamma target genes (G0S2, GPR81,
      GPR109A, and Adipoq) and the protein expression of C/EBPbeta, PPARgamma, and G0S2
      in a dose-dependent manner. Knockdown of C/EBPbeta decreased palmitate-induced
      PPARgamma and its target genes (G0S2, GPR81, GPR109A, and Adipoq) mRNA expression
      and palmitate-induced PPARgamma and G0S2 protein expression in HepG2 cells.
      Knockdown of C/EBPbeta also attenuated lipid accumulation and augmented lipolysis
      in palmitate-treated HepG2 cells. G0S2 knockdown attenuated lipid accumulation
      and augmented lipolysis, while G0S2 knockdown had no effects on the mRNA
      expression of C/EBPbeta, PPARgamma, and PPARgamma target genes (GPR81, GPR109A
      and Adipoq) in palmitate-treated HepG2 cells. CONCLUSION: Palmitate can induce
      lipid accumulation in HepG2 cells by activating C/EBPbeta-mediated G0S2
      expression.

PMID- 29209112
TI  - Epidemiology and natural history of Wilson's disease in the Chinese: A territory
      based study in Hong Kong between 2000 and 2016.
AB  - AIM: To investigate the epidemiology and natural history of Wilson's disease in
      the Chinese. METHODS: Data were retrieved via electronic search of hospital
      medical registry of the Hong Kong Hospital Authority, which covers all the public
      healthcare services. We identified cases of Wilson's disease between 2000 and
      2016 by the International Classification of Diseases (ICD)-9 code. We analyzed
      the incidence rate, prevalence and adverse outcomes of Wilson's disease. RESULTS:
      We identified 211 patients (male cases 104; female cases 107; median age 27.2
      years, IQR: 17.1-38.6 years; duration of follow-up 8.0 years, IQR: 5.0-14.0
      years). The average annual incidence rate was 1.44 per million person-years while
      the prevalence was 17.93 per million. Between 2000 and 2016, there was a decrease
      in the annual incidence rate from 1.65 to 1.23 per million person-years (P =
      0.010), whereas there was an increase in the annual prevalence from 7.80 to 25.20
      per million (P < 0.001). Among the 176 cases with hepatic involvement, 38 (21.6%)
      had cirrhosis, three (1.7%) developed hepatocellular carcinoma, 24 (13.6%)
      underwent liver transplantations, and 26 (14.8%) died. Seven patients had
      concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of
      overall survival were 92.6% and 89.5%, and for transplant-free survival rates
      91.8% and 87.4%, respectively. Cirrhosis and possibly chronic viral hepatitis
      were associated with poorer overall survival. CONCLUSION: There was a significant
      increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was
      favorable except for those with cirrhosis or concomitant viral hepatitis.

PMID- 29209113
TI  - Efficacy of thalidomide therapy in pediatric Crohn's disease with evidence of
      tuberculosis.
AB  - AIM: To evaluate the efficacy of thalidomide for treating troublesome cases of
      pediatric Crohn's disease (CD) with tuberculosis infection. METHODS: A
      retrospective study of clinical outcome among children treated with thalidomide
      was conducted. All patients had evidence of tuberculosis infection with a failure
      of anti-tuberculosis treatment for more than one year, and were subsequently
      diagnosed with CD. All the patients received thalidomide treatment with a
      starting dose of 1.2-2.5 mg/kg per day. Remission was defined as pediatric CD
      activity index less than or equal to 10. RESULTS: Ten patients with CD were
      treated with thalidomide at an average age of 7.2 years and followed up for a
      median of 22.2 mo. Clinical remission rate was 60% after 9-12 mo of thalidomide
      treatment. One patient with no response had an interleukin-10 receptor alpha gene
      mutation. Erythrocyte sedimentation rate, C-reactive protein and platelet count
      showed a dramatic decrease; hemoglobin level and weight improved significantly
      after thalidomide treatment when compared with the baseline values. CONCLUSION:
      Thalidomide is an effective and safe drug for remission of CD in pediatric
      patients who have been treated for tuberculosis.

PMID- 29209114
TI  - Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization
      therapy for hepatocellular carcinoma patients with portal vein tumor thrombus.
AB  - AIM: To evaluate the safety and efficacy of combined endovascular brachytherapy
      (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat
      hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus
      (MPVTT). METHODS: This single-center retrospective study involved 68 patients
      with unresectable HCC or those who were unfit for liver transplantation and
      percutaneous frequency ablation according to the BCLC classification. All
      patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology
      Group (ECOG) performance status of 0-2, and MPVTT. The patients received either
      EVBT with stent placement, TACE, and sorafenib (group A, n = 37), or TACE with
      sorafenib (group B, n = 31). The time to progression (TTP) and overall survival
      (OS) were evaluated by propensity score analysis. RESULTS: In the entire cohort,
      the 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A,
      and 45.8%, 0%, and 0% in group B, respectively (P < 0.001). The median TTP and OS
      were significantly longer in group A than group B (TTP: 9.0 mo vs 3.4 mo, P <
      0.001; OS: 12.3 mo vs 5.2 mo, P < 0.001). In the propensity score-matched cohort,
      the median OS was longer in group A than in group B (10.3 mo vs 6.0 mo, P <
      0.001). Similarly, the median TTP was longer in group A than in group B (9.0 mo
      vs 3.4 mo, P < 0.001). Multivariate Cox analysis revealed that the EVBT combined
      with stent placement, TACE, and sorafenib strategy was an independent predictor
      of favorable OS (HR = 0.18, P < 0.001). CONCLUSION: EVBT combined with stent
      placement, TACE, and sorafenib might be a safe and effective palliative treatment
      option for MPVTT.

PMID- 29209115
TI  - Procedure-related complications in gastric variceal obturation with tissue glue.
AB  - AIM: To focus on procedure-related complications, evaluate their incidence,
      analyze the reasons and discuss the solutions. METHODS: Overall, 628 endoscopic
      gastric variceal obturation (EGVO) procedures (case-times) with NBC were
      performed in 519 patients in the Department of Endoscopy of the Third Affiliated
      Hospital of Sun Yat-Sen University from January 2011 to December 2016. The
      clinical data of patients and procedure-related complications of EGVO were
      retrospectively analyzed. RESULTS: In the 628 EGVO procedures, sticking of the
      needle to the varix occurred in 9 cases (1.43%), including 1 case that used
      lipiodol-diluted NBC and 8 cases that used undiluted NBC (P = 0.000). The needle
      was successfully withdrawn in 8 cases. Large spurt bleeding occurred in one case,
      and hemostasis was achieved by two other injections of undiluted glue. The
      injection catheter became blocked in 17 cases (2.71%) just during the injection,
      and 4 cases were complicated with the needle sticking to the varix. Large glue
      adhesion to the endoscope resulted in difficulty withdrawing the endoscope in 1
      case. Bleeding from multiple sites was observed in the esophagus and gastric
      cardia after the endoscope was withdrawn. Hemostasis was achieved by 1%
      aethoxysklerol injection and intravenous somatostatin. The ligation device stuck
      to the varices in two cases during the subsequent endoscopic variceal ligation.
      In one case, the ligation device was successfully separated from the esophageal
      varix after all bands were released. In another case, a laceration of the vein
      and massive bleeding were observed. The bleeding ceased after 1% aethoxysklerol
      injection. CONCLUSION: Although EGVO with tissue glue is usually safe and
      effective, a series of complications can occur during the procedure that may
      puzzle endoscopists. There is no standard operating procedure for addressing
      these complications. The cases described in the current study can provide some
      reference for others.

PMID- 29209116
TI  - Gastric xanthelasma and metabolic disorders: A large retrospective study among
      Chinese population.
AB  - AIM: To gain knowledge of xanthelasma, a large population-based study was
      conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at
      the First Affiliated Hospital, College of Medicine, Zhejiang University,
      Hangzhou, China during Jan 2009 to Nov 2016 were included. General
      characteristics as well as clinical data were collected, including blood routine,
      serum biochemical analysis, endoscopic findinds, histological evaluation and
      comorbiditie. Statistical analyses was performed using SPSS 20.0 software for
      Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann
      Whitney U test, chi2 test, univariable and multivariable logistic analysis. 2
      tailed P value less than 0.05 was considered to be statistically significant.
      RESULTS: A total of 176006 endoscopies were retrieved and we included 1370
      xanthelasma participants (703 men, 667 women) in this study. Prevalence of
      xanthelasma was 0.78% with average age of 56.6 +/- 11.2 years. Chief complaint of
      xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%),
      abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred
      as single lesion in gastric antrum. Xanthelasma patients witnessed higher
      Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions
      including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma
      patients, serum carcinoembryonic antigen, triglyceride, fasting glucose,
      neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high
      density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma
      accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder
      polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose
      (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P <
      0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all
      independent risk factors in xanthelasma. CONCLUSION: Current study described a
      large xanthelasma cohort in Chinese population, revealed its relationship with H.
      pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.

PMID- 29209117
TI  - Application of superb microvascular imaging in focal liver lesions.
AB  - AIM: To explore the ability of superb microvascular imaging (SMI) in differential
      diagnosis of focal liver lesions (FLLs) and to compare SMI morphology findings to
      those of color Doppler ultrasound and enhanced imaging. METHODS: Twenty-four
      patients with 31 FLLs were included in our study, with diagnoses of hemangioma
      (HE) (n = 17), hepatocellular carcinoma (HCC) (n = 5), metastatic lesions (n =
      5), primary hepatic lymphoma (n = 1), focal nodular hyperplasia (FNH) (n = 2),
      and adenoma (n = 1). Nine lesions were pathologically diagnosed, and 22 lesions
      were radiologically confirmed, all of which were evaluated by at least two types
      of enhanced imaging techniques. All patients had undergone SMI. Patients were
      divided into subgroups based on pathological and radiological diagnoses to
      analyze SMI manifestations. We also compared the SMI manifestations of the most
      common malignant FLLs (HCCs and metastatic lesions) with those of the most common
      benign FLLs (HEs). RESULTS: HEs were classified into three SMI subgroups: diffuse
      dot-like type (n = 6), strip rim type (n = 8), and nodular rim type (n = 3). The
      sizes of the three types of HEs were significantly different (P = 0.00, < 0.05).
      HCCs were classified into two subgroups: diffuse honeycomb type (n = 2) and non
      specific type (n = 3). Four of the metastatic lesions were the strip rim type,
      and the other metastatic lesion was the thick rim type, which is the same as that
      of lymphoma. FNH was described as a spoke-wheel type, and adenoma as a diffuse
      honeycomb type. The SMI types of HCCs and metastatic lesions were significantly
      different from those of HEs (P = 0.048, < 0.05). CONCLUSION: SMI technology
      enables microvascular evaluation of FLLs without using any contrast agent. For
      HEs, lesion size may affect SMI performance. SMI is able to provide useful
      information for differential diagnosis of HCCs and metastatic lesions from HEs.

PMID- 29209118
TI  - Chronic liver disease is universal in children with biliary atresia living with
      native liver.
AB  - AIM: To examine the medical status of children with biliary atresia (BA)
      surviving with native livers. METHODS: In this cross-sectional review, data
      collected included complications of chronic liver disease (CLD) (cholangitis in
      the preceding 12 mo, portal hypertension, variceal bleeding, fractures,
      hepatopulmonary syndrome, portopulmonary hypertension) and laboratory indices
      (white cell and platelet counts, total bilirubin, albumin, international
      normalized ratio, alanine aminotransferase, aspartate aminotransferase, gamma
      glutamyl transpeptidase). Ideal medical outcome was defined as absence of
      clinical evidence of CLD or abnormal laboratory indices. RESULTS: Fifty-two
      children [females = 32, 62%; median age 7.4 years, n = 35 (67%) older than 5
      years] with BA (median age at surgery 60 d, range of 30 to 148 d) survived with
      native liver. Common complications of CLD noted were portal hypertension (40%, n
      = 21; 2 younger than 5 years), cholangitis (36%) and bleeding varices (25%, n =
      13; 1 younger than 5 years). Fifteen (29%) had no clinical complications of CLD
      and three (6%) had normal laboratory indices. Ideal medical outcome was only seen
      in 1 patient (2%). CONCLUSION: Clinical or laboratory evidence of CLD are present
      in 98% of children with BA living with native livers after
      hepatoportoenterostomy. Portal hypertension and variceal bleeding may be seen in
      children younger than 5 years of age, underscoring the importance of medical
      surveillance for complications of BA starting at a young age.

PMID- 29209119
TI  - How severe is moderately severe acute pancreatitis? Clinical validation of
      revised 2012 Atlanta Classification.
AB  - AIM: To explore the outcomes and the appropriate treatment for patients with
      moderately severe acute pancreatitis (AP). METHODS: Statistical analysis was
      performed on data from the prospectively collected database of 103 AP patients
      admitted to the Department of Surgery, Hospital of Lithuanian University of
      Health Sciences in 2008-2013. All patients were confirmed to have the diagnosis
      of AP during the first 24 h following admission. The severity of pancreatitis was
      assessed by MODS and APACHE II scale. Clinical course was re-evaluated after 24,
      48 and 72 h. All patients were categorized into 3 groups based on Atlanta 2012
      classification: Mild, moderately severe, and severe. Outcomes and management in
      moderately severe group were also compared to mild and severe cases according to
      Atlanta 1992 and 2012 classification. RESULTS: Fifty-three-point four percent of
      patients had edematous while 46.6 % were diagnosed with necrotic AP. The most
      common cause of AP was alcohol (42.7%) followed by alimentary (26.2%), biliary
      (26.2%) and idiopathic (4.9%). Under Atlanta 1992 classification 56 (54.4%) cases
      were classified as "mild" and 47 (45.6%) as "severe". Using the revised
      classification (Atlanta 2012), the patient stratification was different: 49
      (47.6%) mild, 27 (26.2%) moderately severe and 27 (26.2%) severe AP cases. The
      two severe groups (Atlanta 1992 and Revised Atlanta 2012) did not show
      statistically significant differences in clinical parameters, including ICU stay,
      need for interventional treatment, infected pancreatic necrosis or mortality
      rates. The moderately severe group of 27 patients (according to Atlanta 2012) had
      significantly better outcomes when compared to those 47 patients classified as
      severe form of AP (according to Atlanta 1992) with lower incidence of necrosis
      and sepsis, lower APACHE II (P = 0.002) and MODS (P = 0.001) scores, shorter ICU
      stay, decreased need for interventional and surgical treatment. CONCLUSION: Study
      shows that Atlanta 2012 criteria are more accurate, reduce unnecessary treatments
      for patients with mild and moderate severe pancreatitis, potentially resulting in
      health costs savings.

PMID- 29209120
TI  - Laparoscopic VS open hepatectomy for hepatolithiasis: An updated systematic
      review and meta-analysis.
AB  - AIM: To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver
      resection for treating hepatolithiasis. METHODS: We conducted a systematic
      literature search on PubMed, Embase, Web of Science and Cochrane Library, and
      undertook a meta-analysis to compare the efficacy and safety of laparoscopic
      hepatectomy VS conventional open liver resection for local hepatolithiasis in the
      left or right lobe. Intraoperative and postoperative outcomes (time, estimated
      blood loss, blood transfusion rate, postoperative intestinal function recovery
      time, length of hospital stay, postoperative complication rate, initial residual
      stone, final residual stone and stone recurrence) were analyzed systematically.
      RESULTS: A comprehensive literature search retrieved 16 publications with a total
      of 1329 cases. Meta-analysis of these studies showed that the laparoscopic
      approach for hepatolithiasis was associated with significantly less
      intraoperative estimated blood loss [weighted mean difference (WMD): 61.56, 95%
      confidence interval (CI): 14.91-108.20, P = 0.01], lower blood transfusion rate
      [odds ratio (OR): 0.41, 95%CI: 0.22-0.79, P = 0.008], shorter intestinal function
      recovery time (WMD: 0.98, 95%CI: 0.47-1.48, P = 0.01), lower total postoperative
      complication rate (OR: 0.52, 95%CI: 0.39-0.70, P < 0.0001) and shorter stay in
      hospital (WMD: 3.32, 95%CI: 2.32-4.32, P < 0.00001). In addition, our results
      showed no significant differences between the two groups in operative time (WMD:
      21.49, 95%CI: 0.27-43.24, P = 0.05), residual stones (OR: 0.79, 95%CI: 0.50-1.25,
      P = 0.31) and stone recurrence (OR: 0.34, 95%CI: 0.11-1.08, P = 0.07).
      Furthermore, with subgroups analysis, our results proved that the laparoscopic
      approach for hepatolithiasis in the left lateral lobe and left side could achieve
      satisfactory therapeutic effects. CONCLUSION: The laparoscopic approach is safe
      and effective, with less intraoperative estimated blood loss, fewer postoperative
      complications, reduced length of hospital stay and shorter intestinal function
      recovery time than with conventional approaches.

PMID- 29209121
TI  - Fatal gastrointestinal histoplasmosis 15 years after orthotopic liver
      transplantation.
AB  - We report a case of ileo-colonic Histoplasmosis without apparent respiratory
      involvement in a patient who had previously undergone an orthotopic liver
      transplant (OLT) for primary biliary cholangitis 15 years earlier. The recipient
      lived in the United Kingdom, a non-endemic region for Histoplasmosis. However,
      she had previously lived in rural southern Africa prior to her OLT. The patient
      presented with iron deficiency anaemia, diarrhoea, abdominal pain and progressive
      weight loss. She reported no previous foreign travel, however, it later became
      known that following her OLT she had been on holiday to rural southern Africa. On
      investigation, a mild granulomatous colitis primarily affecting the right colon
      was identified, that initially improved with mesalazine. Her symptoms worsened
      after 18 mo with progressive ulceration of her distal small bowel and right
      colon. Mycobacterial, Yersinia, cytomegalovirus and human immunodeficiency virus
      infections were excluded and the patient was treated with prednisolone for a
      working diagnosis of Crohn's disease. Despite some early symptom improvement
      following steroids, there was subsequent deterioration with the patient
      developing gram-negative sepsis and multi-organ failure, leading to her death.
      Post-mortem examination revealed that her ileo-colonic inflammation was caused by
      Histoplasmosis.

PMID- 29209122
TI  - Advances in endoscopic balloon therapy for weight loss and its limitations.
AB  - The field of medical and surgical weight loss is undergoing an explosion of new
      techniques and devices. A lot of these are geared towards endoscopic approaches
      rather than the conventional and more invasive laparoscopic or open approach. One
      such recent advance is the introduction of intrgastric balloons. In this article,
      we discuss the recently Food and Drug Administration approved following balloons
      for weight loss: the OrberaTM Intragastric Balloon System (Apollo Endosurgery
      Inc, Austin, TX, United States), the ReShape(r) Integrated Dual Balloon System
      (ReShape Medical, Inc., San Clemente, CA, United States), and the Obalon
      (Obalon(r) Therapeutics, Inc.). The individual features of each of these
      balloons, the method of introduction and removal, and the expected weight loss
      and possible complications are discussed. This review of the various balloons
      highlights the innovation in the field of weight loss.

PMID- 29209123
TI  - Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal
      copy number aberration data.
AB  - AIM: To identify chromosomal copy number aberrations (CNAs) in early-stage
      hepatocellular carcinoma (HCC) and analyze whether they are correlated with
      patient prognosis. METHODS: One hundred and twenty patients with early-stage HCC
      were enrolled in our study, with the collection of formalin fixed, paraffin
      embedded (FFPE) specimens and clinicopathological data. Tumor areas were marked
      by certified pathologists on a hematoxylin and eosin-stained slide, and cancer
      and adjacent non-cancerous tissues underwent extraction of DNA, which was
      analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of
      heterozygosity (LOH). Ten individuals with nonmalignant disease were used as the
      control group. Another cohort consisting of 40 patients with stage I/II HCC were
      enrolled to analyze gene expression and to correlate findings with the OncoScan
      data. RESULTS: Copy number amplifications occurred at chromosomes 1q21.1-q44 and
      8q12.3-24.3 and deletions were found at 4q13.1-q35.2, 8p 23.2-21.1, 16q23.3-24.3,
      and 17p13.3-12, while LOH commonly occurred at 1p32.3, 3p21.31, 8p23.2-21.1,
      16q22.1-24.3, and 17p 13.3-11 in early-stage HCC. Using Cox regression analysis,
      we also found that a higher percentage of genome change (>= 60%) was an
      independent factor for worse prognosis in early-stage HCC (P = 0.031). Among the
      875 genes in the OncoScan GeneChip, six were independent predictors of worse
      disease-free survival, of which three were amplified (MYC, ELAC2, and SYK) and
      three were deleted (GAK, MECOM, and WRN). Further, patients with HCC who
      exhibited >= 3 CNAs involving these six genes have worse outcomes compared to
      those who had < 3 CNAs (P < 0.001). Similarly, Asian patients with stage I HCC
      from The Cancer Genome Atlas harboring CNAs with these genes were also predicted
      to have poorer outcomes. CONCLUSION: Patients with early-stage HCC and increased
      genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk
      for poorer outcome after resection.

PMID- 29209124
TI  - Composition and immuno-stimulatory properties of extracellular DNA from mouse gut
      flora.
AB  - AIM: To demonstrate that specific bacteria might release bacterial extracellular
      DNA (eDNA) to exert immunomodulatory functions in the mouse small intestine.
      METHODS: Extracellular DNA was extracted using phosphate buffered saline with 0.5
      mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell
      impermeant and high-affinity nucleic acid stain, was used to confirm the
      existence of eDNA in the mucus layers of the small intestine and colon in healthy
      Male C57BL/6 mice. Composition difference of eDNA and intracellular DNA (iDNA) of
      the small intestinal mucus was studied by Illumina sequencing and terminal
      restriction fragment length polymorphism (T-RFLP). Stimulation of cytokine
      production by eDNA was studied in RAW264.7 cells in vitro. RESULTS: TOTO-1 iodide
      staining confirmed existence of eDNA in loose mucus layer of the mouse colon and
      thin surface mucus layer of the small intestine. Illumina sequencing analysis and
      T-RFLP revealed that the composition of the eDNA in the small intestinal mucus
      was significantly different from that of the iDNA of the small intestinal mucus
      bacteria. Illumina Miseq sequencing showed that the eDNA sequences came mainly
      from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant
      bacteria of the small intestinal flora comprised Gram-positive bacteria. Both
      eDNA and iDNA were added to native or lipopolysaccharide-stimulated Raw267.4
      macrophages, respectively. The eDNA induced significantly lower tumor necrosis
      factor-alpha/interleukin-10 (IL-10) and IL-6/IL-10 ratios than iDNA, suggesting
      the predominance for maintaining immune homeostasis of the gut. CONCLUSION: Our
      results indicated that degraded bacterial genomic DNA was mainly released by Gram
      negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in
      gut mucus of mice. They decreased pro-inflammatory activity compared to total gut
      flora genomic DNA.

PMID- 29209125
TI  - Transmitted cardiovascular pulsations on high resolution esophageal impedance
      manometry, and their significance in dysphagia.
AB  - AIM: To investigate the behavior of pulsatile pressure zones (PPZ's) as noted on
      high resolution esophageal impedance manometry (HREIM), and determine their
      association with dysphagia. METHODS: Retrospective, single center case control
      design screening HREIM studies for cases (dysphagia) and controls (no dysphagia).
      Thoracic radiology studies were reviewed further in cases for (thoracic
      cardiovascular) thoracic cardiovascular (TCV) structures in esophageal proximity
      to compare with HREIM findings. Manometric data was collected for number,
      location, axial length, PPZ pressure and esophageal clearance function
      (impedance). RESULTS: Among 317 screened patients, 56% cases and 64% controls had
      PPZ's. Fifty cases had an available thoracic radiology comparison. The
      distribution of PPZ's in these 50 cases and 59 controls was similar (average 1.4
      PPZ/patient). Controls (mean 31.2 +/- SD 12 years) were a significantly younger
      population than cases (mean 67.3 +/- SD 14.9 years) with P < 0.0001. The upright
      posture PPZ pressure was higher in controls (15.7 +/- 10.0 mmHg) than cases (10.8
      +/- 9.7 mmHg). Although statistically significant (P = 0.005), it was a weak
      predictor using logistic regression and ROC model (AUC = 0.65). Three dysphagia
      patients had partial compression from external TCV on radiology (1 aberrant
      subclavian artery, 2 dilated left atrium). The posture (supine vs upright) with
      more prominent PPZ's impaired bolus clearance in 9 additional cases by > 20%.
      CONCLUSION: Transmitted TCV pulsations observed in HREIM bear no significant
      impact on swallowing. However, in older adults with dysphagia, evidence of
      impaired bolus clearance on impedance should be evaluated for external TCV
      compression. These associations have never been explored previously in
      literature, and are novel.

PMID- 29209126
TI  - Intestinal parameters of oxidative imbalance in celiac adults with
      extraintestinal manifestations.
AB  - AIM: To evaluate selected intestinal parameters of oxidative stress, and
      antioxidant capacity in adult celiac disease patients with extraintestinal
      manifestations. METHODS: The study involved 85 adult patients divided into the
      following subgroups: (1) patients with newly diagnosed celiac disease (CD) (n =
      7); (2) celiac patients not adhering to a gluten-free diet (GFD) (n = 22); (3)
      patients with CD on the GFD (n = 31); and (4) patients with functional disorders
      of the gastrointestinal tract, serving as controls (n = 25). Celiac patients
      presented with non-classic symptoms or extraintestinal manifestations. Standard
      blood tests including serum antioxidant levels (uric acid, bilirubin, and vitamin
      D), celiac antibody levels, and histopathological status of duodenal biopsy
      specimens have been determined. The expression of mRNA for tumor necrosis factor
      alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 10 (IL-10),
      superoxide dismutase (SOD), heat-shock protein 70 (HSP-70), hypoxia-inducible
      factor 1 (HIF-1alpha), and BAX in the duodenal mucosa of patients was analyzed by
      reverse transcriptase-polymerase chain reaction. RESULTS: The mean plasma uric
      acid level in patients with active CD (newly diagnosed and nonadherent patients)
      and treated celiac patients was significantly higher than in controls (260.17 +/-
      53.65 vs 190.8 +/- 22.98, P < 0.001, and 261.7 +/- 51.79 vs 190.8 +/- 22.98, P <
      0.001, respectively). The mean bilirubin concentration in active and treated
      celiac patients was significantly lower than in controls (8.23 +/- 5.04 vs 10.48
      +/- 4.08, P < 0.05 and 8.06 +/- 3.31 vs 10.48 +/- 4.08, P < 0.05, respectively).
      The mean plasma vitamin D level was significantly lower in active celiac patients
      than in treated celiac patients and controls (19.37 +/- 9.03 vs 25.15 +/- 11.2, P
      < 0.05 and 19.37 +/- 9.03 vs 29.67 +/- 5.12, P < 0.001, respectively). The
      expression of TNF-alpha, IL-10, and HSP-70 mRNAs was significantly elevated in
      the celiac groups regardless of the diet when compared with controls. Patients on
      the GFD presented a significantly lower mRNA expression of TNF-alpha and IL-10
      than in newly diagnosed and nonadherent patients (P < 0.05). The expression of
      SOD mRNA was significantly elevated in celiac patients compared with controls (P
      < 0.05), with a significant difference between treated and untreated patients (P
      < 0.05). The expression of HIF-1alpha mRNA and BAX mRNA was significantly higher
      in patients with active CD compared with controls and patients on GFD, while no
      difference was observed between the latter two groups. CONCLUSION: Increased
      intestinal expression of HSP-70 despite GFD indicates that GFD only partially
      reduced oxidative stress. CD patients exhibited an oxidative imbalance and
      inflammatory response despite GFD. Uric acid may act as an important antioxidant
      in CD.

PMID- 29209127
TI  - Prediction of hepatocellular carcinoma development by aminotransferase to
      platelet ratio index in primary biliary cholangitis.
AB  - AIM: To investigate the usefulness of aspartate aminotransferase to platelet
      ratio index (APRI) in predicting hepatocellular carcinoma (HCC) risk in primary
      biliary cholangitis (PBC). METHODS: We identified PBC patients between 2000 and
      2015 by searching the electronic medical database of a tertiary center. The
      hazard ratio (HR) of HCC with different risk factors was determined by Cox
      proportional hazards model. RESULTS: One hundred and forty-four PBC patients were
      recruited. Patients were diagnosed at a median age of 57.8 years [interquartile
      range (IQR): 48.7-71.5 years), and 41 (28.5%) patients had cirrhosis at baseline.
      The median follow-up duration was 6.9 years (range: 1.0-26.3 years). Twelve
      patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient
      years. The overall 5-, 10- and 15-year cumulative incidences of HCC were 2.3%
      95%CI: 0%-4.8%), 8.4% (95%CI: 1.8%-14.5%) and 21.6% (6.8%-34.1%), respectively.
      Older age (HR = 1.07), cirrhosis (HR = 4.38) and APRI at 1 year after treatment
      (APRI-r1) > 0.54 (HR = 3.94) were independent factors for HCC development. APRI
      r1, when combined with treatment response, further stratified HCC risk (log rank
      P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC
      was 0.77 (95%CI: 0.64-0.88). CONCLUSION: APRI-r1 can be used to predict the
      development of HCC in PBC patients. Combination of APRI-r1 with treatment
      response can further stratify the HCC risk.

PMID- 29209128
TI  - Role of combined propofol and sufentanil anesthesia in endoscopic injection
      sclerotherapy for esophageal varices.
AB  - AIM: To investigate the efficacy and safety of a combination of sufentanil and
      propofol injection in patients undergoing endoscopic injection sclerotherapy
      (EIS) for esophageal varices (EVs). METHODS: Patients with severe EVs who
      underwent EIS with sufentanil and propofol anesthesia between April 2016 and July
      2016 at our hospital were reviewed. Although EIS and sequential therapy were
      performed under endotracheal intubation, we only evaluated the efficacy and
      safety of anesthesia for the first EIS procedure. Patients were intravenously
      treated with 0.5-1 MUg/kg sufentanil. Anesthesia was induced with 1-2 mg/kg
      propofol and maintained using 2-5 mg/kg per hour of propofol. Information,
      regarding age, sex, weight, American Association of Anesthesiologists (ASA)
      physical status, Child-Turcotte-Pugh (CTP) classification, indications,
      preanesthetic problems, endoscopic procedure, successful completion of the
      procedure, anesthesia time, recovery time, and anesthetic agents, was recorded.
      Adverse events, including hypotension, hypertension, bradycardia, and hypoxia,
      were also noted. RESULTS: Propofol and sufentanil anesthesia was provided in 182
      procedures involving 140 men and 42 women aged 56.1 +/- 11.7 years (range, 25-83
      years). The patients weighed 71.4 +/- 10.7 kg (range, 45-95 kg) and had ASA
      physical status classifications of II (79 patients) or III (103 patients). Ninety
      five patients had a CTP classification of A and 87 had a CTP classification of B.
      Intravenous anesthesia was successful in all cases. The mean anesthesia time was
      33.1 +/- 5.8 min. The mean recovery time was 12.3 +/- 3.7 min. Hypotension
      occurred in two patients (1.1%, 2/182). No patient showed hypertension during the
      endoscopic therapy procedure. Bradycardia occurred in one patient (0.5%, 1/182),
      and hypoxia occurred in one patient (0.5%, 1/182). All complications were easily
      treated with no adverse sequelae. All endoscopic procedures were completed
      successfully. CONCLUSION: The combined use of propofol and sufentanil injection
      in endotracheal intubation-assisted EIS for EVs is effective and safe.

PMID- 29209129
TI  - Health disparities are associated with gastric cancer mortality-to-incidence
      ratios in 57 countries.
AB  - AIM: To evaluate the association between mortality-to-incidence ratios (MIRs) and
      health disparities. METHODS: In this study, we used the GLOBOCAN 2012 database to
      obtain the cancer incidence and mortality data for 57 countries, and combined
      this information with the World Health Organization (WHO) rankings and total
      expenditures on health/gross domestic product (e/GDP). The associations between
      variables and MIRs were analyzed by linear regression analyses and the 57
      countries were selected according to their data quality. RESULTS: The more
      developed regions showed high gastric cancer incidence and mortality crude rates,
      but lower MIR values than the less developed regions (0.64 vs 0.80,
      respectively). Among six continents, Oceania had the lowest (0.60) and Africa had
      the highest (0.91) MIR. A good WHO ranking and a high e/GDP were significantly
      associated with low MIRs (P = 0.001 and P = 0.001, respectively). CONCLUSION: The
      MIR variation for gastric cancer would predict regional health disparities.

PMID- 29209130
TI  - Circulating miR-125a but not miR-125b is decreased in active disease status and
      negatively correlates with disease severity as well as inflammatory cytokines in
      patients with Crohn's disease.
AB  - AIM: To determine the association of circulating miR-125a/b expression with the
      risk and disease severity of Crohn's disease (CD), and with inflammatory
      cytokines. METHODS: Plasma samples were collected from patients with active CD (A
      CD), or CD in remission (R-CD) and from healthy controls (HCs). The levels of the
      inflammatory cytokines interleukin-17 (IL-17), tumour necrosis factor-alpha (TNF
      alpha), and interferon-gamma (IFN-gamma) were measured by enzyme-linked
      immunosorbent assay. The expression of miR-125a/b was assessed by quantitative
      polymerase chain reaction (qPCR). RESULTS: Twenty-nine A-CD patients, 37 R-CD
      patients, and 37 HCs were included in the study. Plasma miR-125a expression was
      decreased in A-CD patients compared with that in R-CD patients (P < 0.001) and
      HCs (P < 0.001). miR-125a expression levels enabled the differentiation of A-CD
      from R-CD patients [area under curve (AUC) = 0.854] and from HCs (AUC = 0.780),
      whereas miR-125b expression did not. miR-125a was negatively correlated with C
      reaction protein (CRP) (P = 0.017), erythrocyte sedimentation rate (ESR) (P =
      0.026), Crohn's disease activity index (CDAI) (P = 0.003), IL-17 (P = 0.015), and
      TNF-alpha (P = 0.004) in A-CD patients. Furthermore, miR-125a was negatively
      associated with CRP (P = 0.038) and CDAI (P = 0.021) in R-CD patients. Regarding
      miR-125b, no association with CRP, CDAI, IL-17, TNF-alpha, or IFN-gamma was found
      in A-CD or in R-CD patients. miR-125a levels gradually increased in A-CD patients
      who achieved clinical remission (P = 0.009) after 3-mo treatment, whereas they
      remained unchanged among patients who failed to achieve remission. No changes in
      miR-125b expression were detected in remission or non-remission patients after
      treatment. CONCLUSION: Circulating miR-125a but not miR-125b is decreased in
      patients with active disease status and negatively correlates with disease
      severity and inflammatory cytokines in patients with CD.

PMID- 29209131
TI  - Dramatic response of hepatitis C patients chronically infected with hepatitis C
      virus genotype 3 to sofosbuvir-based therapies in Punjab, Pakistan: A prospective
      study.
AB  - AIM: To prospectively evaluate the efficacy of sofobuvir (SOF) in hepatitis C
      patients infected with hepatitis C virus (HCV) genotype 3 in Pakistan. METHODS:
      The present study was performed with the coordination of gastroenterology and
      pathology departments of Shalamar Hospital Lahore from August 2014 to May 2016.
      The total number of patients included in this study was 1375 and all of them were
      infected with HCV genotype 3. On the basis of drug combinations, all the patients
      were separated into two groups. The first group of patients was treated for 24 wk
      with SOF (Sovaldi(r) by Gilead Sciences) plus ribavirin (RBV) [Ribazol(r) by Getz
      Pharma Pakistan (PVT) Ltd], while the patients of the second group were treated
      with SOF + RBV + pegylated-interferon (pegIFN) alfa-2a (Ropegra by Roach) for 12
      wk. HCV genotyping and viral load measurement were performed on fully automated
      Abbott Real-Time PCR system (Abbott m24sp automated nucleic acid extraction
      system and Abbott m2000rt amplification system; abbott Molecular, Des Plaines,
      IL, United States). For the assessment of sustained virological response (SVR),
      all HCV RNA negative patients were followed for 12 weeks after the treatment
      completion. Any patient with less than 12 IU/mL viral load after 12 wk of
      treatment completion was considered as a sustained virological responder (SVR
      12). RESULTS: A total of 1375 patients chronically infected with HCV genotype 3
      were treated with two drug combinations SOF + RBV and SOF + RBV + pegIFN alfa-2a.
      On the basis of these drug combinations, patients were divided into two groups
      (first and second). Overall SVR-12 was excellent in both groups (99.17% and
      97.91%). Older patients (> 40 years) of second group showed lower SVR-12 (93.46%)
      compared to first group older patients (98.79%), while in the younger patients of
      both groups, the SVR-12 rate was almost the same (99.54% in first group and
      99.05% in second group). No such difference regarding SVR-12 rate was seen in
      males and females of first group patients (99.68% and 98.88%, respectively),
      while in second group the males were found to be better responders compared to
      females (98.96% and 95%). The SVR-12 rate in previously treated patients of first
      group was better (99.34%) than second group (93.70%), while naive patients of
      second group were marginally better responders (99.25%) than first group
      (97.80%). Rapid viral response at week-4 was found to be a very effective
      predictor for assessing the SVR rate at this stage of therapy in both groups.
      Headache, anemia and fatigue were common side effects in both groups either
      treated with SOF + RBV or SOF + RBV + pegIFN alfa-2a, while the overall
      percentage of the side effects was higher in second group. CONCLUSION: The
      remarkable SVR response rate of HCV genotype 3 infected patients to SOF provided
      a new way to look forward to eliminate hepatitis C from our region.

PMID- 29209132
TI  - Short-term clinical outcomes of laparoscopic vs open rectal excision for rectal
      cancer: A systematic review and meta-analysis.
AB  - AIM: To review evidence on the short-term clinical outcomes of laparoscopic (LRR)
      vs open rectal resection (ORR) for rectal cancer. METHODS: A systematic
      literature search was performed using Cochrane Central Register, MEDLINE, EMBASE,
      Scopus, OpenGrey and ClinicalTrials.gov register for randomized clinical trials
      (RCTs) comparing LRR vs ORR for rectal cancer and reporting short-term clinical
      outcomes. Articles published in English from January 1, 1995 to June, 30 2016
      that met the selection criteria were retrieved and reviewed. The Preferred
      Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statements
      checklist for reporting a systematic review was followed. Random-effect models
      were used to estimate mean differences and risk ratios. The robustness and
      heterogeneity of the results were explored by performing sensitivity analyses.
      The pooled effect was considered significant when P < 0.05. RESULTS: Overall, 14
      RCTs were included. No differences were found in postoperative mortality (P =
      0.19) and morbidity (P = 0.75) rates. The mean operative time was 36.67 min
      longer (95%CI: 27.22-46.11, P < 0.00001), the mean estimated blood loss was 88.80
      ml lower (95%CI: -117.25 to -60.34, P < 0.00001), and the mean incision length
      was 11.17 cm smaller (95%CI: -13.88 to -8.47, P < 0.00001) for LRR than ORR.
      These results were confirmed by sensitivity analyses that focused on the four
      major RCTs. The mean length of hospital stay was 1.71 d shorter (95%CI: -2.84 to 
      0.58, P < 0.003) for LRR than ORR. Similarly, bowel recovery (i.e., day of the
      first bowel movement) was 0.68 d shorter (95%CI: -1.00 to -0.36, P < 0.00001) for
      LRR. The sensitivity analysis did not confirm a significant difference between
      LRR and ORR for these latter two parameters. The overall quality of the evidence
      was rated as high. CONCLUSION: LRR is associated with lesser blood loss, smaller
      incision length, and longer operative times compared to ORR. No differences are
      observed for postoperative morbidity and mortality.

PMID- 29209133
TI  - Anterior vs conventional approach right hepatic resection for large
      hepatocellular carcinoma: A systematic review and meta-analysis.
AB  - AIM: To compare the clinical outcomes of right hepatectomy for large
      hepatocellular carcinoma via the anterior and conventional approach. METHODS: We
      comprehensively performed an electronic search of PubMed, EMBASE, and the
      Cochrane Library for randomized controlled trials (RCTs) or controlled clinical
      trials (CCTs) published between January 2000 and May 2017 concerning the anterior
      approach (AA) and the conventional approach (CA) to right hepatectomy. Studies
      that met the inclusion criteria were included, and their outcome analyses were
      further assessed using a fixed or random effects model. RESULTS: This analysis
      included 2297 patients enrolled in 16 studies (3 RCTs and 13 CTTs).
      Intraoperative blood loss [weighted mean difference = -255.21; 95% confidence
      interval (95%CI): -371.3 to -139.12; P < 0.0001], intraoperative blood
      transfusion [odds ratio (OR) = 0.42; 95%CI: 0.29-0.61; P < 0.0001], mortality (OR
      = 0.59; 95%CI: 0.38-0.92; P = 0.02), morbidity (OR = 0.77; 95%CI: 0.62-0.95; P =
      0.01), and recurrence rate (OR = 0.62; 95%CI: 0.47-0.83; P = 0.001) were
      significantly reduced in the AA group. Patients in the AA group had better
      overall survival (hazard ratio [HR] = 0.71; 95%CI: 0.50-1.00; P = 0.05) and
      disease-free survival (HR = 0.67; 95%CI: 0.58-0.79; P < 0.0001) than those in the
      CA group. CONCLUSION: The AA is safe and effective for right hepatectomy for
      large hepatocellular carcinoma and could accelerate postoperative recovery and
      achieve better survival outcomes than the CA.

PMID- 29209134
TI  - Metabolically based liver damage pathophysiology in patients with urea cycle
      disorders - A new hypothesis.
AB  - : The underlying pathophysiology of liver dysfunction in urea cycle disorders
      (UCDs) is still largely elusive. There is some evidence that the accumulation of
      urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is
      possible that liver injury is directly caused by the toxicity of ammonia. The
      rarity of UCDs, the lack of checking of iron level in these patients, superficial
      knowledge of UC and an underestimation of the metabolic role of fumaric acid, are
      the main reasons that are responsible for the incomprehension of the mechanism of
      liver injury in patients suffering from UCDs. Owing to our routine clinical
      practice to screen for iron overload in severely ill neonates, with the focus on
      the newborns suffering from acute liver failure, we report a case of
      citrullinemia with neonatal liver failure and high blood parameters of iron
      overload. We hypothesize that the key is in the decreased-deficient fumaric acid
      production in the course of UC in UCDs that causes several sequentially
      intertwined metabolic disturbances with final result of liver iron overload. The
      presented hypothesis could be easily tested by examining the patients suffering
      from UCDs, for liver iron overload. This could be easily performed in countries
      with a high population and comprehensive national register for inborn errors of
      metabolism. CONCLUSION: Providing the hypothesis is correct, neonatal liver
      damage in patients having UCD can be prevented by the supplementation of pregnant
      women with fumaric or succinic acid, prepared in the form of iron supplementation
      pills. After birth, liver damage in patients having UCDs can be prevented by
      supplementation of these patients with zinc fumarate or zinc succinylate, as
      well.

PMID- 29209135
TI  - First case of cross-auxiliary double domino donor liver transplantation.
AB  - We report a case of double domino liver transplantation in a 32-year-old woman
      who was diagnosed with familial amyloid polyneuropathy (FAP) and liver
      dysfunction. A two-stage surgical plan was designed, and one domino graft was
      implanted during each stage. During the first stage, an auxiliary domino liver
      transplantation was conducted using a domino graft from a 4-year-old female child
      with Wilson's disease. After removing the right lobe of the FAP patient's liver,
      the graft was rotated 90 degrees counterclockwise and placed along the right side
      of the inferior vena cava (IVC). The orifices of the left, middle, and right
      hepatic veins were reconstructed using an iliac vein patch and then anastomosed
      to the right side of the IVC. Thirty days later, a second domino liver graft was
      implanted. The second domino graft was from a 3-year-old female child with an
      ornithine carbamyl enzyme defect, and it replaced the residual native liver (left
      lobe). To balance the function and blood flow between the two grafts, a
      percutaneous transcatheter selective portal vein embolization was performed, and
      "the left portal vein" of the first graft was blocked 9 mo after the second
      transplantation. The liver function indices, blood ammonia, and 24-h urinary
      copper levels were normal at the end of a 3-year follow-up. These two domino
      donor grafts from donors with different metabolic disorders restored normal liver
      function. Our experience demonstrated a new approach for resolving metabolic
      disorders with domino grafts and utilizing explanted livers from children.

PMID- 29209136
TI  - Interaction between Flow Diverter and Parent Artery of Intracranial Aneurysm: A
      Computational Study.
AB  - To evaluate the influence of deployment strategy on the mechanical interaction
      between braided stent and parent artery of intracranial aneurysm (the elasticity
      of the arterial wall is considered), finite-element analyses are carried out by
      referring to computational models of flow-diverter device and arterial wall. Two
      implantation strategies are used to virtually implant the braided stent into the
      ideal intracranial aneurysm model. One is the noncompacted implantation method,
      and the other is the implantation method of using push-pull technique. During the
      process of the implantation, the changes of the arterial shape around the
      aneurysm and the changes of the wall pressure at the contact area between the
      braided stent and the inner wall of the artery are analyzed. The results indicate
      that the average contact pressure in the area of low porosity is 57 mmHg using
      the push-pull technique, and the average contact pressure of the parent artery is
      10.45 mmHg using the non-push-pull technique. The diameter of the parent artery
      at the aneurismal orifice increased about 0.2 mm when using the push-pull
      technique, so the elasticity of the vessel should be considered in the mechanical
      analysis of interaction between stent and vessel.

PMID- 29209137
TI  - Corrigendum to "Incorporating Family Function into Chronic Pain Disability: The
      Role of Catastrophizing".
AB  - [This corrects the article DOI: 10.1155/2016/6838596.].

PMID- 29209138
TI  - Effects of Glutathione on Mechanical Allodynia and Central Sensitization in
      Chronic Postischemic Pain Rats.
AB  - Background: The chronic postischemia pain (CPIP) model is an animal model using
      ischemia/reperfusion injury that mimics the symptoms of complex regional pain
      syndrome type I. Glutathione (GSH) prevents ischemia/reperfusion injury by
      scavenging free radicals. We conducted this study to investigate the protective
      effect of GSH in CPIP rats via changes of mechanical allodynia and
      phospholyration of the N-methyl-D-aspartate receptor subunit GluN1. Methods: We
      divided 45 rats into 5 groups: sham, CPIP, CPIP + GSH 100 mg/kg, CPIP + GSH 200
      mg/kg, and CPIP + GSH 500 mg/kg. Rats in the sham and CPIP groups received normal
      saline and rats in the other groups received GSH at the designated doses thirty
      minutes prior to reperfusion. Withdrawal thresholds were evaluated before sugery
      as well as 1, 3, and 7 days after surgery. pGluN1 level in the spinal cord was
      also measured. Results: GSH treated rats show a significant increase in the
      withdrawal thresholds of both hind paws as compared with the CPIP group dose
      dependently. The expression of pGluN1 in the GSH treated rats significantly
      decreased as compared to the CPIP group (all P < 0.05). Conclusion: These
      findings suggest that GSH inhibited the development of mechanical allodynia and
      central sensitization in CPIP rats.

PMID- 29209139
TI  - Bayes' theorem, the ROC diagram and reference values: Definition and use in
      clinical diagnosis.
AB  - Medicine is diagnosis, treatment and care. To diagnose is to consider the
      probability of the cause of discomfort experienced by the patient. The physician
      may face many options and all decisions are liable to uncertainty to some extent.
      The rational action is to perform selected tests and thereby increase the pre
      test probability to reach a superior post-test probability of a particular
      option. To draw the right conclusions from a test, certain background information
      about the performance of the test is necessary. We set up a partially artificial
      dataset with measured results obtained from the laboratory information system and
      simulated diagnosis attached. The dataset is used to explore the use of
      contingency tables with a unique graphic design and software to establish and
      compare ROC graphs. The loss of information in the ROC curve is compensated by a
      cumulative data analysis (CDA) plot linked to a display of the efficiency and
      predictive values. A standard for the contingency table is suggested and the use
      of dynamic reference intervals discussed.

PMID- 29209140
TI  - Role of matrix metalloproteinase-2/9 (MMP2/9) in lead-induced changes in an in
      vitro blood-brain barrier model.
AB  - Lead (Pb) is a well-known neurotoxicant and a risk factor for neurologic
      disorders. The blood brain barrier (BBB) plays an important role in the
      maintenance of optimal brain function. BBB is a target of Pb, and studies have
      shown that Pb induced barrier loss and decreased the expression of tight junction
      proteins, but the detailed mechanisms are not fully understood. Matrix
      metalloproteinases (MMPs) are important components of extracellular matrix
      proteasome and can affect the remodeling and degradation of tight junction (TJ).
      The role of MMP-2/9 in Pb-induced damage of BBB is not known. In our study, we
      used an in vitro BBB model by co-culturing human umbilical vascular endothelial
      cells (ECV304 cells) with rat glioma cells (C6 cells), and detected the
      expression of related TJ proteins and MMP-2/9. Our results showed that Pb
      increased the permeability of the in vitro BBB model, and stimulating C6 cells
      with Pb could decrease the protein level of ZO-1 (zonula occludens-1) and
      occludin in ECV304 cells. Pb could increase the mRNA and protein level of MMP-2/9
      in C6 cells, and inhibition of MMP-2/9 by SB-3CT could partially alleviate Pb
      induced down-regulation of TJ proteins in ECV304 cells and Pb-induced barrier
      damage in the in vitro BBB model. Our research established potential therapeutic
      targets for modulating and preserving optimal BBB function.

PMID- 29209141
TI  - Co-expression network analysis identified FCER1G in association with progression
      and prognosis in human clear cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common solid lesion within
      kidney, and its prognostic is influenced by the progression covering a complex
      network of gene interactions. In current study, the microarray data GSE66272
      containing ccRCC and adjacent normal tissues was analyzed to identify 4042
      differentially expressed genes, on which weighted gene co-expression network
      analysis was performed. Then 12 co-expressed gene modules were identified. The
      highest association was found between blue module and pathological stage (r = 
      0.77) by Pearson's correlation analysis. Functional enrichment analysis revealed
      that biological processes of blue module focused on inflammatory response, immune
      response, chemotaxis (all p < 1e-10). In the significant module, a total of 38
      network hub genes were identified, FCER1G exhibited the highest correlation (r =
      0.95) with ccRCC progression. In addition, FCER1G was hub node in the protein
      protein interaction network of the genes in blue module as well. Thus, FCER1G was
      subsequently selected for validation. In the test set GSE53757 and RNA-sequencing
      data, FCER1G expression was also positively correlated with four stages of ccRCC
      progression (p < 0.001). Receiver operating characteristic (ROC) curve indicated
      that FCER1G could distinguish localized (pathological stage I, II) from non
      localized (pathological stage III, IV) ccRCC (AUC=0.74, p < 0.001). Besides,
      FCER1G could be a prognostic gene in clinical practice as well, revealed by
      survival analysis based on RNA-sequencing data (p < 0.05). In conclusion, using
      weighted gene co-expression analysis, FCER1G was identified and validated in
      association with ccRCC progression and prognosis, which might improve the
      prognosis by influencing immune-related pathways.

PMID- 29209142
TI  - Clinical and in vitro analysis of Osteopontin as a prognostic indicator and
      unveil its potential downstream targets in bladder cancer.
AB  - Osteopontin (OPN) plays an important role in cancer progression, however its
      prognostic significance and its downstream factors are largely elusive. In this
      study, we have shown that expression of OPN was significantly higher in bladder
      cancer specimens with higher T-stage or tumor grades. In addition, a high level
      of OPN was significantly associated with poorer survival in two independent
      bladder cancer patient cohorts totaling 389 bladder cancer patients with
      available survival data. We further identified Matrix metallopeptidase 9 (MMP9)
      and S100 calcium-binding protein A8 (S100A8) were both downstream factors for OPN
      in bladder cancer specimens and bladder cancer cell lines. Expression of OPN was
      significantly positively associated with that of MMP9 and S100A8, while
      overexpression of OPN resulted in upregulation of MMP9 and S100A8, and knockdown
      of OPN showed consistent downregulation of MMP9 and S100A8 expression levels.
      Importantly, expression levels of both MMP9 and S100A8 were significantly
      associated with higher T-stage, higher tumor grade and a shorter survival time in
      the bladder cancer patients. Interestingly, OPN expression only predicted
      survival in MMP9-high, but not MMP9-low subgroups, and in S100A8-low but not
      S100A8-high subgroups. Our results suggest that OPN, MMP9 and S100A8 all play a
      significant role in bladder cancer progression and are potential prognostic
      markers and therapeutic targets in bladder cancer. The mechanistic link between
      these three genes and bladder cancer progression warrants further investigation.

PMID- 29209143
TI  - Risk Factors and Preventions of Breast Cancer.
AB  - Breast cancer is the second leading cause of cancer deaths among women. The
      development of breast cancer is a multi-step process involving multiple cell
      types, and its prevention remains challenging in the world. Early diagnosis of
      breast cancer is one of the best approaches to prevent this disease. In some
      developed countries, the 5-year relative survival rate of breast cancer patients
      is above 80% due to early prevention. In the recent decade, great progress has
      been made in the understanding of breast cancer as well as in the development of
      preventative methods. The pathogenesis and tumor drug-resistant mechanisms are
      revealed by discovering breast cancer stem cells, and many genes are found
      related to breast cancer. Currently, people have more drug options for the
      chemoprevention of breast cancer, while biological prevention has been recently
      developed to improve patients' quality of life. In this review, we will summarize
      key studies of pathogenesis, related genes, risk factors and preventative methods
      on breast cancer over the past years. These findings represent a small step in
      the long fight against breast cancer.

PMID- 29209144
TI  - Targeting the long noncoding RNA MALAT1 blocks the pro-angiogenic effects of
      osteosarcoma and suppresses tumour growth.
AB  - Osteosarcoma (OS), the commonest primary malignant tumour originating from bone,
      affects a substantial number of people, mostly during adolescent growth, and
      leads to a very poor prognosis as a result of the high rate of early metastases.
      Consequently, there is urgent demand for a novel treatment for this disease.
      There are growing concerns focused on OS-induced pro-angiogenic effects, but to
      date, the mechanism of OS-induced pro-angiogenesis is still insufficiently well
      understood. Long noncoding RNAs (lncRNAs) have attracted increasing interest due
      to their strong correlation with a variety of diseases and their powerful
      capacity for epigenetic regulation. Recently, metastasis-associated lung
      adenocarcinoma transcript 1 (MALAT1), a lncRNA, has been discovered to be closely
      related to OS progression and hypoxia responses which are associated with
      angiogenesis. In this study, we confirm that MALAT1 induces pro-angiogenic
      effects, and demonstrate that the underlying mechanism involves a
      MALAT1/mechanistic target of rapamycin (mTOR)/hypoxia inducible factor-1alpha
      (HIF-1alpha) loop. With the help of chemically-modified small interfering RNAs
      targeting MALAT1 (siMALAT1), we confirm that siMALAT could provide a potential
      strategy to block the abnormally active OS-induced pro-angiogenic effect, and
      ultimately successfully suppress progression of OS tumours.

PMID- 29209145
TI  - Altered Neuroendocrine Immune Responses, a Two-Sword Weapon against Traumatic
      Inflammation.
AB  - During the occurrence and development of injury (trauma, hemorrhagic shock,
      ischemia and hypoxia), the neuroendocrine and immune system act as a prominent
      navigation leader and possess an inter-system crosstalk between the reciprocal
      information dissemination. The fundamental reason that neuroendocrinology and
      immunology could mix each other and permeate toward the field of traumatology is
      owing to their same biological languages or chemical information molecules
      (hormones, neurotransmitters, neuropeptides, cytokines and their corresponding
      receptors) shared by the neuroendocrine and immune systems. The immune system is
      not only modulated by the neuroendocrine system, but also can modulate the
      biological functions of the neuroendocrine system. The interactive linkage of
      these three systems precipitates the complicated space-time patterns for the
      courses of traumatic inflammation. Recently, compelling evidence indicates that
      the network linkage pattern that initiating agents of neuroendocrine responses,
      regulatory elements of immune cells and effecter targets for immune regulatory
      molecules arouse the resistance mechanism disorders, which supplies the
      beneficial enlightenment for the diagnosis and therapy of traumatic complications
      from the view of translational medicine. Here we review the alternative
      protective and detrimental roles as well as possible mechanisms of the
      neuroendocrine immune responses in traumatic inflammation.

PMID- 29209146
TI  - Adhesion Regulating Molecule 1 Mediates HAP40 Overexpression-Induced
      Mitochondrial Defects.
AB  - Striatal neuron death in Huntington's disease is associated with abnormal
      mitochondrial dynamics and functions. However, the mechanisms for this
      mitochondrial dysregulation remain elusive. Increased accumulation of Huntingtin
      associated protein 40 (HAP40) has been shown to be associated with Huntington's
      disease. However, the link between increased HAP40 and Huntington's disease
      remains largely unknown. Here we show that HAP40 overexpression causes
      mitochondrial dysfunction and reduces cell viability in the immortalized mouse
      striatal neurons. HAP40-associated mitochondrial dysfunction is associated with
      reduction of adhesion regulating molecule 1 (ADRM1) protein. Consistently,
      depletion of ADRM1 by shRNAs impaired mitochondrial functions and increased
      mitochondrial fragmentation in mouse striatal cells. Moreover, reducing ADRM1
      levels enhanced activity of fission factor dynamin-related GTPase protein 1
      (Drp1) via increased phosphorylation at serine 616 of Drp1 (Drp1Ser616).
      Restoring ADRM1 protein levels was able to reduce HAP40-induced ROS levels and
      mitochondrial fragmentation and improved mitochondrial functions and cell
      viability. Moreover, reducing Drp1 activity by Drp1 inhibitor, Mdivi-1,
      ameliorates both HAP40 overexpression- and ADRM1 depletion-induced mitochondrial
      dysfunction. Taken together, our studies suggest that HAP40-mediated reduction of
      ADRM1 alters the mitochondrial fission activity and results in mitochondrial
      fragmentation and mitochondrial dysfunction.

PMID- 29209147
TI  - Transcriptome integration analysis in hepatocellular carcinoma reveals discordant
      intronic miRNA-host gene pairs in expression.
AB  - Intronic miRNAs, residing in intronic regions of host genes, are thought to be co
      transcribed from their host genes and present consistent expression patterns with
      host genes. Recent studies reported a few intronic miRNAs with discordant
      expression with their host genes. We therefore aimed to understand the expression
      pattern of intronic miRNAs and their host genes in hepatocellular carcinoma (HCC)
      and reveal possible associated molecular mechanisms. Our genome wide integration
      analysis of miRNA and mRNA transcriptomes, in three dataset from 550 patients
      with HCC, found that a large amount of miRNA-host gene pairs were discordantly
      expressed. Consistent results were also revealed in 775 breast cancer patients.
      Further, most of HCC-related intronic miRNAs were predicted to have distinct
      upstream regulators and independent proximal promoter signals from host genes.
      The discordant expression of representative pairs, miR-26s/CTDSPs, was validated
      experimentally. We have also identified the independent transcriptional start
      site, promoter signal, and transcriptional factor of miR-26b from its host gene.
      Collectively, discordant expression of intronic miRNAs and their host genes was
      relatively ubiquitous and the intronic miRNA "independent transcription" may
      partially contribute to such a phenotype.

PMID- 29209148
TI  - Human colorectal cancer progression correlates with LOX-induced ECM stiffening.
AB  - Some solid tumors are characterized by extracellular matrix (ECM) remodeling and
      stiffening, which is related to solid tumor progression and aggression. However,
      the relationship between ECM stiffness and colorectal cancer (CRC) remains
      unclear. In this study, we investigated the relevance of ECM stiffness to
      clinicopathologic features using human CRC tissue microarrays. The results
      demonstrate that the expression of ECM components in CRC tissues is closely
      correlated with CRC progression and poor prognosis, which indicates that ECM
      stiffness may be associated with CRC development. We further studied lysyl
      oxidase (LOX) expression in CRC tissue and demonstrated that LOX expression is
      closely correlated with CRC progression. Previous studies showed that P-selectin
      mediated platelet accumulation in CRC tissue may up-regulate LOX expression. Our
      findings indicate that P-selectin-mediated platelet aggregation may up-regulate
      LOX expression and enhance the remodeling and stiffening of the tumor ECM, which
      may promote the progression of colorectal cancer. Therefore, LOX may be a
      potential effective therapeutic target to treat colorectal cancer.

PMID- 29209149
TI  - Electroencephalographic evaluation of acoustic therapies for the treatment of
      chronic and refractory tinnitus.
AB  - Background: To date, a large number of acoustic therapies have been applied to
      treat tinnitus. The effect that produces those auditory stimuli is, however, not
      well understood yet. Furthermore, the conventional clinical protocol is based on
      a trial-error procedure, and there is not a formal and adequate treatment follow
      up. At present, the only way to evaluate acoustic therapies is by means of
      subjective methods such as analog visual scale and ad-hoc questionnaires.
      Methods: This protocol seeks to establish an objective methodology to treat
      tinnitus with acoustic therapies based on electroencephalographic (EEG) activity
      evaluation. On the hypothesis that acoustic therapies should produce perceptual
      and cognitive changes at a cortical level, it is proposed to examine neural
      electrical activity of patients suffering from refractory and chronic tinnitus in
      four different stages: at the beginning of the experiment, at one week of
      treatment, at five weeks of treatment, and at eight weeks of treatment. Four of
      the most efficient acoustic therapies found at the moment are considered:
      retraining, auditory discrimination, enriched acoustic environment, and binaural.
      Discussion: EEG has become a standard brain imaging tool to quantify and qualify
      neural oscillations, which are basically spatial, temporal, and spectral patterns
      associated with particular perceptual, cognitive, motor and emotional processes.
      Neural oscillations have been traditionally studied on the basis of event-related
      experiments, where time-locked and phase-locked responses (i.e., event-related
      potentials) along with time-locked but not necessary phase-locked responses
      (i.e., event-related (de) synchronization) have been essentially estimated. Both
      potentials and levels of synchronization related to auditory stimuli are herein
      proposed to assess the effect of acoustic therapies. Trial registration:
      Registration Number: ISRCTN14553550. ISRCTN Registry: BioMed Central. Date of
      Registration: October 31st, 2017.

PMID- 29209150
TI  - Correlation between subjective and objective hearing tests after unilateral and
      bilateral cochlear implantation.
AB  - Background: There are many methods for assessing hearing performance after
      cochlear implantation. Standard evaluations often encompass objective hearing
      tests only, while patients' subjective experiences gain importance in today's
      healthcare. The aim of the current study was to analyze the correlation between
      subjective (self-reported questionnaires) and objective (speech perception and
      localization) hearing test results in adult cochlear implant (CI) users.
      Secondary, the correlation between subjective and objective hearing tests was
      compared between bilateral and unilateral CI patients. Methods: Data for this
      study were prospectively collected as part of a multicentre randomized controlled
      trial. Thirty-eight postlingually deafened adult patients were randomly allocated
      to receive either unilateral (n = 19) or bilateral (n = 19) cochlear
      implantation. We used data gathered after one year of follow-up. We studied the
      correlation between objectively measured speech perception and localization
      skills on the one hand and related domains of the Speech, Spatial and Qualities
      of Hearing Scale (SSQ) and Nijmegen Cochlear Implant Questionnaire (NCIQ) on the
      other hand. We also compared these correlations between unilateral and bilateral
      CI users. Results: We found significant weak to moderate negative correlations
      between the subjective test results (speech domain of the SSQ and the advanced
      speech perception domain of the NCIQ) and the related objective speech perception
      in noise test results (r = -0.33 to -0.48). A significant moderate correlation
      was found between the subjective test results (spatial domain of the SSQ) and the
      related objective localization test results (r = 0.59). The correlations in the
      group of bilateral CI patients (r = -0.28 to -0.54) did not differ significantly
      from the correlations in the group of unilateral CI patients (r = 0.15 to -0.40).
      Conclusions: Current objective tests do not fully reflect subjective everyday
      listening situations. This study elucidates the importance and necessity of
      questionnaires in the evaluation of cochlear implantation. Therefore, it is
      advised to evaluate both objective and subjective tests in CI patients on a
      regular basis. Trial registration: This trial was registered on March 11, 2009 in
      the Dutch Trial Register. Trial registration number: NTR1722.

PMID- 29209151
TI  - Endoscopic repair of lateral sphenoid Encephaloceles: a case series.
AB  - Background: Lateral sphenoid encephaloceles present a surgical challenge. These
      encephaloceles may be difficult to access given their lateral location and
      proximity to the neural and vascular structures of the sphenoid floor,
      pterygopalatine fossa, and lateral and superior sphenoid walls. Additionally,
      many patients have idiopathic intracranial hypertension, increasing the risk of
      recurrence. When untreated or undiscovered, these encephaloceles increase the
      risk of meningitis. Methods: All consecutive endoscopic repairs of lateral
      sphenoid encephaloceles by a single surgeon from 2012 to 2017 were analyzed for
      method of repair, complications, and recurrence rate. Odds ratio for recurrence
      of CSF leak for Alloderm inlay/abdominal fat sphenoid obliteration/nasoseptal
      flap with multilayer repair vs. other method (Alloderm onlay/contralateral
      nasoseptal flap or free mucosal graft) was compared, and Fischer's exact test was
      used to calculate the two-sided p-value for the two repair methods. Results: The
      success rate (no recurrence of cerebrospinal fluid rhinorrhea) for Alloderm
      inlay/abdominal fat onlay/nasoseptal flap onlay was 100% while for Alloderm
      onlay/contralateral nasoseptal flap + free mucosal graft the success rate was 0%.
      For any nasoseptal flap repair vs. free mucosal graft the success rates were
      83.3% and 16.7% respectively. The success rate for Alloderm inlay/abdominal fat
      onlay/nasoseptal flap onlay vs. Alloderm onlay/contralateral nasoseptal flap +
      free mucosal graft was statistically significant (p = 0.048), but the success
      rate for any nasoseptal flap repair vs. free mucosal graft was not significant (p
      = 0.29). The success rate for patients without post-op lumbar drain vs. with post
      op lumbar drain was also nonsignificant (p = 0.29). Conclusions: In the author's
      hands Alloderm inlay/abdominal fat onlay/nasoseptal flap onlay was superior to
      other repair methods (Alloderm onlay/contralateral nasoseptal flap or free middle
      turbinate mucosa onlay graft). The complication rate was low. Post-operative
      lumbar drainage did not affect the success rate.

PMID- 29209152
TI  - Natural agents mediated autophagic signal networks in cancer.
AB  - Recent studies suggested that natural compounds are important in finding targets
      for cancer treatments. Autophagy ("self-eating") plays important roles in
      multiple diseases and acts as a tumor suppressor in cancer. Here, we examined the
      molecular mechanism by which natural agents regulate autophagic signals.
      Understanding the relationship between natural agents and cellular autophagy may
      provide more information for cancer diagnosis and chemoprevention.

PMID- 29209153
TI  - RAC3 influences the chemoresistance of colon cancer cells through autophagy and
      apoptosis inhibition.
AB  - Background: RAC3 coactivator overexpression has been implicated in tumorigenesis,
      contributing to inhibition of apoptosis and autophagy. Both mechanisms are
      involved in resistance to treatment with chemotherapeutic agents. The aim of this
      study was to investigate its role in chemoresistance of colorectal cancer.
      Methods: The sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells
      HT-29, HCT 116 and Lovo cell lines, expressing high or low natural levels of
      RAC3, was investigated using viability assays. Results: In HCT 116 cells, we
      found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy was
      strongly induced, while oxaliplatin has shown a similar ability to induce both of
      them. However, in HCT 116 cells expressing a short hairpin RNA for RAC3, we found
      an increased sensitivity to both drugs if it is compared with control cells. 5
      Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent
      apoptosis and produce an increase of autophagy. In addition, both process have
      shown to be trigged faster than in control cells, starting earlier after
      stimulation. Conclusions: Our results suggest that RAC3 expression levels
      influence the sensitivity to chemotherapeutic drugs. Therefore, the knowledge of
      RAC3 expression levels in tumoral samples could be an important contribution to
      design new improved therapeutic strategies in the future.

PMID- 29209154
TI  - Effects of two pre-workout supplements on concentric and eccentric force
      production during lower body resistance exercise in males and females: a
      counterbalanced, double-blind, placebo-controlled trial.
AB  - Background: Pre-workout supplements purportedly enhance feelings of energy,
      reduce fatigue and improve exercise performance. The purpose of this study was to
      examine the performance effects of caffeinated and non-caffeinated multi
      ingredient pre-workout supplements. Methods: In a counterbalanced, double-blind,
      placebo-controlled design, eccentric and concentric force production during lower
      body resistance exercise on a mechanized squat device were assessed after
      supplement ingestion. Repetitions-in-reserve/RPE and subjective feelings of
      energy, focus and fatigue were also examined. Twenty-one resistance-trained
      adults (12 F, 9 M) completed three conditions in random order: caffeinated
      supplement, non-caffeinated supplement and placebo. Subjects were not informed of
      the presence of a placebo condition. Thirty minutes after supplement ingestion, a
      3-repetition maximum test and 5 sets of 6 repetitions were completed using the
      squat device. Each repetition involved 4-s eccentric and concentric phases, and
      the force signal throughout each repetition was sampled from a load cell
      contained within the squat device. The scaled and filtered force signals were
      analyzed using customized software. Repeated measures analysis of variance and
      appropriate follow-up analyses were utilized to compare dependent variables, and
      relevant effect sizes (d) were calculated. Results: Supplement or placebo
      ingestion led to similar subjective responses (p > 0.05). Energy (+8 to 44%; d =
      0.3 to 0.8) and focus (+8 to 25%; d = 0.3 to 0.5) were acutely increased by
      supplement or placebo ingestion and decreased as the exercise session progressed.
      Fatigue was acutely decreased by supplement or placebo ingestion (-7 to 38%; d = 
      0.1 to -0.6) and increased as the exercise session progressed. Eccentric and
      concentric forces were unimproved by supplementation during the exercise sets for
      both sexes. In the non-caffeinated supplement condition only, maximal eccentric
      force production was lower during sets 3 to 5, as compared to set 1 (p < 0.05).
      Effect size data indicated that both the caffeinated and non-caffeinated
      supplements may contribute to small increases in concentric force production in
      males (+5 to 20%, d = 0.2 to 0.4 relative to placebo), but not females.
      Conclusions: As compared to placebo, caffeinated and non-caffeinated multi
      ingredient pre-workout supplements failed to improve concentric and eccentric
      force production. In males, effect size data indicate a possible small benefit of
      supplementation on concentric force production, although this was not
      statistically significant. When resistance-trained subjects were unaware of the
      presence of a placebo, resistance exercise performance was similar regardless of
      whether a placebo or multi-ingredient supplement was ingested.

PMID- 29209155
TI  - Optimization of quantitative proteomic analysis of clots generated from plasma of
      patients with venous thromboembolism.
AB  - Background: It is well known that fibrin network binds a large variety of
      proteins, including inhibitors and activators of fibrinolysis, which may affect
      clot properties, such as stability and susceptibility to fibrinolysis. Specific
      plasma clot composition differs between individuals and may change in disease
      states. However, the plasma clot proteome has not yet been in-depth analyzed,
      mainly due to technical difficulty related to the presence of a highly abundant
      protein-fibrinogen and fibrin that forms a plasma clot. Methods: The aim of our
      study was to optimize quantitative proteomic analysis of fibrin clots prepared ex
      vivo from citrated plasma of the peripheral blood drawn from patients with prior
      venous thromboembolism (VTE). We used a multiple enzyme digestion filter aided
      sample preparation, a multienzyme digestion (MED) FASP method combined with LC
      MS/MS analysis performed on a Proxeon Easy-nLC System coupled to the Q Exactive
      HF mass spectrometer. We also evaluated the impact of peptide fractionation with
      pipet-tip strong anion exchange (SAX) method on the obtained results. Results:
      Our proteomic approach revealed 476 proteins repeatedly identified in the plasma
      fibrin clots from patients with VTE including extracellular vesicle-derived
      proteins, lipoproteins, fibrinolysis inhibitors, and proteins involved in immune
      responses. The MED FASP method using three different enzymes: LysC, trypsin and
      chymotrypsin increased the number of identified peptides and proteins and their
      sequence coverage as compared to a single step digestion. Peptide fractionation
      with a pipet-tip strong anion exchange (SAX) protocol increased the depth of
      proteomic analyses, but also extended the time needed for sample analysis with LC
      MS/MS. Conclusions: The MED FASP method combined with a label-free quantification
      is an excellent proteomic approach for the analysis of fibrin clots prepared ex
      vivo from citrated plasma of patients with prior VTE.

PMID- 29209156
TI  - Machine Learning Classification Combining Multiple Features of A Hyper-Network of
      fMRI Data in Alzheimer's Disease.
AB  - Exploring functional interactions among various brain regions is helpful for
      understanding the pathological underpinnings of neurological disorders. Brain
      networks provide an important representation of those functional interactions,
      and thus are widely applied in the diagnosis and classification of
      neurodegenerative diseases. Many mental disorders involve a sharp decline in
      cognitive ability as a major symptom, which can be caused by abnormal
      connectivity patterns among several brain regions. However, conventional
      functional connectivity networks are usually constructed based on pairwise
      correlations among different brain regions. This approach ignores higher-order
      relationships, and cannot effectively characterize the high-order interactions of
      many brain regions working together. Recent neuroscience research suggests that
      higher-order relationships between brain regions are important for brain network
      analysis. Hyper-networks have been proposed that can effectively represent the
      interactions among brain regions. However, this method extracts the local
      properties of brain regions as features, but ignores the global topology
      information, which affects the evaluation of network topology and reduces the
      performance of the classifier. This problem can be compensated by a subgraph
      feature-based method, but it is not sensitive to change in a single brain region.
      Considering that both of these feature extraction methods result in the loss of
      information, we propose a novel machine learning classification method that
      combines multiple features of a hyper-network based on functional magnetic
      resonance imaging in Alzheimer's disease. The method combines the brain region
      features and subgraph features, and then uses a multi-kernel SVM for
      classification. This retains not only the global topological information, but
      also the sensitivity to change in a single brain region. To certify the proposed
      method, 28 normal control subjects and 38 Alzheimer's disease patients were
      selected to participate in an experiment. The proposed method achieved
      satisfactory classification accuracy, with an average of 91.60%. The abnormal
      brain regions included the bilateral precuneus, right parahippocampal
      gyrus?hippocampus, right posterior cingulate gyrus, and other regions that are
      known to be important in Alzheimer's disease. Machine learning classification
      combining multiple features of a hyper-network of functional magnetic resonance
      imaging data in Alzheimer's disease obtains better classification performance.

PMID- 29209157
TI  - The Effect of Head Model Simplification on Beamformer Source Localization.
AB  - Beamformers are a widely-used tool in brain analysis with magnetoencephalography
      (MEG) and electroencephalography (EEG). For the construction of the beamformer
      filters realistic head volume conductor modeling is necessary for accurately
      computing the EEG and MEG leadfields, i.e., for solving the EEG and MEG forward
      problem. In this work, we investigate the influence of including realistic head
      tissue compartments into a finite element method (FEM) model on the beamformer's
      localization ability. Specifically, we investigate the effect of including
      cerebrospinal fluid, gray matter, and white matter distinction, as well as
      segmenting the skull bone into compacta and spongiosa, and modeling white matter
      anisotropy. We simulate an interictal epileptic measurement with white sensor
      noise. Beamformer filters are constructed with unit gain, unit array gain, and
      unit noise gain constraint. Beamformer source positions are determined by
      evaluating power and excess sample kurtosis (g2) of the source-waveforms at all
      source space nodes. For both modalities, we see a strong effect of modeling the
      cerebrospinal fluid and white and gray matter. Depending on the source position,
      both effects can each be in the magnitude of centimeters, rendering their
      modeling necessary for successful localization. Precise skull modeling mainly
      effected the EEG up to a few millimeters, while both modalities could profit from
      modeling white matter anisotropy to a smaller extent of 5-10 mm. The unit noise
      gain or neural activity index beamformer behaves similarly to the array gain
      beamformer when noise strength is sufficiently high. Variance localization seems
      more robust against modeling errors than kurtosis.

PMID- 29209158
TI  - Induced Pluripotent Stem Cell-Derived Neural Stem Cell Transplantations Reduced
      Behavioral Deficits and Ameliorated Neuropathological Changes in YAC128 Mouse
      Model of Huntington's Disease.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder characterized
      by neuronal loss and motor dysfunction. Although there is no effective treatment,
      stem cell transplantation offers a promising therapeutic strategy, but the safety
      and efficacy of this approach needs to be optimized. The purpose of this study
      was to test the potential of intra-striatal transplantation of induced
      pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For
      this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them
      into neural stem cells in vitro, labeled them with Hoechst, and transplanted them
      bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice. We
      assessed the efficiency of these transplanted iPS-NSCs to reduce motor deficits
      in YAC128 mice by testing them on an accelerating rotarod task at 1 day prior to
      transplantation, and then weekly for 10 weeks. Our results showed an amelioration
      of locomotor deficits in YAC128 mice that received iPS-NSC transplantations.
      Following testing, the mice were sacrificed, and their brains were analyzed using
      immunohistochemistry and Western blot (WB). The results from our histological
      examinations revealed no signs of tumors and evidence that many iPS-NSCs survived
      and differentiated into region-specific neurons (medium spiny neurons) in both WT
      and HD mice, as confirmed by co-labeling of Hoechst-labeled transplanted cells
      with NeuN and DARPP-32. Also, counts of Hoechst-labeled cells revealed that a
      higher proportion were co-labeled with DARPP-32 and NeuN in HD-, compared to WT-
      mice, suggesting a dissimilar differentiation pattern in HD mice. Whereas
      significant decreases were found in counts of NeuN- and DARPP-32-labeled cells,
      and for neuronal density measures in striata of HD vehicle controls, such
      decrements were not observed in the iPS-NSCs-transplanted-HD mice. WB analysis
      showed increase of BDNF and TrkB levels in striata of transplanted HD mice
      compared to HD vehicle controls. Collectively, our data suggest that iPS-NSCs may
      provide an effective option for neuronal replacement therapy in HD.

PMID- 29209159
TI  - Interference between Space and Time Estimations: From Behavior to Neurons.
AB  - Influences between time and space can be found in our daily life in which we are
      surrounded by numerous spatial metaphors to refer to time. For instance, when we
      move files from one folder to another in our computer a horizontal line that
      grows from left to right informs us about the elapsed and remaining time to
      finish the procedure and, similarly, in our communication we use several spatial
      terms to refer to time. Although with some differences in the degree of
      interference, not only space has an influence on time but both magnitudes
      influence each other. Indeed, since our childhood our estimations of time are
      influenced by space even when space should be irrelevant and the same occurs when
      estimating space with time as distractor. Such interference between magnitudes
      has also been observed in monkeys even if they do not use language or computers,
      suggesting that the two magnitudes are tightly coupled beyond communication and
      technology. Imaging and lesion studies have indicated that same brain areas are
      involved during the processing of both magnitudes and have suggested that rather
      than coding the specific magnitude itself the brain represents them as abstract
      concepts. Recent neurophysiological studies in prefrontal cortex, however, have
      shown that the coding of absolute and relative space and time in this area is
      realized by independent groups of neurons. Interestingly, instead, a high overlap
      was observed in this same area in the coding of goal choices across tasks. These
      results suggest that rather than during perception or estimation of space and
      time the interference between the two magnitudes might occur, at least in the
      prefrontal cortex, in a subsequent phase in which the goal has to be chosen or
      the response provided.

PMID- 29209161
TI  - Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3
      Signaling Pathway in the Descending Pain Modulation System.
AB  - Electroacupuncture (EA) has been used for treating visceral hypersensitivity
      (VH). However, the underlying molecular mechanism remains unclear. This study was
      aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA
      attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of
      transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the
      rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis.
      Methods: Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro
      benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40%
      ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7,
      then every 3 days for six times. VH was assessed by visceromotor response (VMR)
      and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension
      pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh
      thoracic vertebra and the brain were collected at day 22. The protein and mRNA
      levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and
      qPCR, respectively. The distribution of these substances was observed with
      immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus
      raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal
      motor nucleus of vagi (DMV). Results: Goats administered with TNBS-ethanol
      solution showed diarrhea, enhanced VMR and pain behavior response, and increased
      IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and
      DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and
      pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG,
      NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA
      level of these three substances in the SCDH. Conclusion: EA attenuates VH
      probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH
      axis.

PMID- 29209160
TI  - Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes.
AB  - Antipsychotic drugs (APDs) are widely prescribed to control various mental
      disorders. As mental disorders are chronic diseases, these drugs are often used
      over a life-time. However, APDs can cause serious glucometabolic side-effects
      including type 2 diabetes and hyperglycaemic emergency, leading to medication non
      compliance. At present, there is no effective approach to overcome these side
      effects. Understanding the mechanisms for APD-induced diabetes should be helpful
      in prevention and treatment of these side-effects of APDs and thus improve the
      clinical outcomes of APDs. In this review, the potential mechanisms for APD
      induced diabetes are summarized so that novel approaches can be considered to
      relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple
      mechanisms: (1) APDs can inhibit the insulin signaling pathway in the target
      cells such as muscle cells, hepatocytes and adipocytes to cause insulin
      resistance; (2) APD-induced obesity can result in high levels of free fatty acids
      (FFA) and inflammation, which can also cause insulin resistance. (3) APDs can
      cause direct damage to beta-cells, leading to dysfunction and apoptosis of beta
      cells. A recent theory considers that both beta-cell damage and insulin
      resistance are necessary factors for the development of diabetes. In high-fat
      diet-induced diabetes, the compensatory ability of beta-cells is gradually
      damaged, while APDs cause direct beta-cell damage, accounting for the severe form
      of APD-induced diabetes. Based on these mechanisms, effective prevention of APD
      induced diabetes may need an integrated approach to combat various effects of
      APDs on multiple pathways.

PMID- 29209162
TI  - Characterization of Cochlear, Vestibular and Cochlear-Vestibular Electrically
      Evoked Compound Action Potentials in Patients with a Vestibulo-Cochlear Implant.
AB  - The peripheral vestibular system is critical for the execution of activities of
      daily life as it provides movement and orientation information to motor and
      sensory systems. Patients with bilateral vestibular hypofunction experience a
      significant decrease in quality of life and have currently no viable treatment
      option. Vestibular implants could eventually restore vestibular function. Most
      vestibular implant prototypes to date are modified cochlear implants to fast
      track development. These use various objective measurements, such as the
      electrically evoked compound action potential (eCAP), to supplement behavioral
      information. We investigated whether eCAPs could be recorded in patients with a
      vestibulo-cochlear implant. Specifically, eCAPs were successfully recorded for
      cochlear and vestibular setups, as well as for mixed cochlear-vestibular setups.
      Similarities and slight differences were found for the recordings of the three
      setups. These findings demonstrated the feasibility of eCAP recording with a
      vestibulo-cochlear implant. They could be used in the short term to reduce
      current spread and avoid activation of non-targeted neurons. More research is
      warranted to better understand the neural origin of vestibular eCAPs and to
      utilize them for clinical applications.

PMID- 29209163
TI  - Voluntary Ambulation by Upper Limb-Triggered HAL(r) in Patients with Complete
      Quadri/Paraplegia Due to Chronic Spinal Cord Injury.
AB  - Patients with complete paraplegia after spinal cord injury (SCI) are unable to
      stand or walk on their own. Standing exercise decreases the risk of decubitus
      ulcers, osteoporosis, and joint deformities in patients with SCI. Conventional
      gait training for complete paraplegia requires excessive upper limb usage for
      weight bearing and is difficult in cases of complete quadriplegia. The purpose of
      this study was to describe voluntary ambulation triggered by upper limb activity
      using the Hybrid Assistive Limb(r) (HAL) in patients with complete
      quadri/paraplegia after chronic SCI. Four patients (3 men, 1 woman) were enrolled
      in this study. The mean patient age +/- standard deviation was 37.2 +/- 17.8
      (range, 20-67) years. Clinical evaluation before intervention revealed the
      following findings: case 1, neurological level C6, American Spinal Cord Injury
      Association impairment scale (AIS) grade B; case 2, T6, AIS A; case 3, T10 AIS A;
      and case 4, T11, AIS A. The HAL intervention consisted of 10 sessions. Each HAL
      session lasted 60-90 min. The HAL electrodes for hip and knee flexion-extension
      were placed on the anterior and posterior sides of the upper limbs
      contralaterally corresponding to each of the lower limbs. Surface
      electromyography (EMG) was used to evaluate muscle activity of the tensor fascia
      lata and quadriceps femoris (Quad) in synchronization with a Vicon motion capture
      system. The modified Ashworth scale (mAs) score was also evaluated before and
      after each session. All participants completed all 10 sessions. Cases 1, 2, and 3
      demonstrated significant decreases in mAs score after the sessions compared to
      pre-session measurements. In all cases, EMG before the intervention showed no
      apparent activation in either Quad. However, gait phase dependent activity of the
      lower limb muscles was seen during voluntarily triggered ambulation driven by
      upper limb muscle activities. In cases 3 and 4, active contraction in both Quads
      was observed after intervention. These findings suggest that upper-limb-triggered
      HAL ambulation is a safe and feasible option for rehabilitation in patients with
      complete quadri/paraplegia caused by chronic SCI.

PMID- 29209164
TI  - Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and
      Regenerating Nervous Systems.
AB  - In both the central nervous system (CNS) and the peripheral nervous system (PNS),
      axonal injury induces changes in neuronal gene expression. In the PNS, a
      relatively well-characterized alteration in transcriptional activation is known
      to promote axonal regeneration. This transcriptional cascade includes the
      neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act
      to facilitate successful axon regeneration in the PNS, this process does not
      occur in the CNS. The present study examines the differential expression of Sox11
      and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at
      different time points: (i) the acutely injured CNS (retina after optic nerve
      crush) and PNS (dorsal root ganglion after sciatic nerve crush), (ii) a CNS
      regeneration model (retina after optic nerve crush and induced regeneration); and
      (iii) the retina during a chronic form of central neurodegeneration (the DBA/2J
      glaucoma model). We find an initial increase of Sox11 in both PNS and CNS after
      injury; however, the expression of Bdnf isoforms is higher in the PNS relative to
      the CNS. Sustained upregulation of Sox11 is seen in the injured retina following
      regeneration treatment, while the expression of two Bdnf mRNA isoforms is
      suppressed. Furthermore, two isoforms of Sox11 with different 3'UTR lengths are
      present in the retina, and the long isoform is specifically upregulated in later
      stages of glaucoma. These results provide insight into the molecular cascades
      active during axonal injury and regeneration in mammalian neurons.

PMID- 29209165
TI  - MicroRNA-133b Negatively Regulates Zebrafish Single Mauthner-Cell Axon
      Regeneration through Targeting tppp3 in Vivo.
AB  - Axon regeneration, fundamental to nerve repair, and functional recovery, relies
      on rapid changes in gene expression attributable to microRNA (miRNA) regulation.
      MiR-133b has been proved to play an important role in different organ
      regeneration in zebrafish, but its role in regulating axon regeneration in vivo
      is still controversial. Here, combining single-cell electroporation with a vector
      based miRNA-expression system, we have modulated the expression of miR-133b in
      Mauthner-cells (M-cells) at the single-cell level in zebrafish. Through in vivo
      imaging, we show that overexpression of miR-133b inhibits axon regeneration,
      whereas down-regulation of miR-133b, promotes axon outgrowth. We further show
      that miR-133b regulates axon regeneration by directly targeting a novel
      regeneration-associated gene, tppp3, which belongs to Tubulin polymerization
      promoting protein family. Gain or loss-of-function of tppp3 experiments indicated
      that tppp3 was a novel gene that could promote axon regeneration. In addition, we
      observed a reduction of mitochondrial motility, which have been identified to
      have a positive correlation with axon regeneration, in miR-133b overexpressed M
      cells. Taken together, our work provides a novel way to study the role of miRNAs
      in individual cell and establishes a critical cell autonomous role of miR-133b in
      zebrafish M-cell axon regeneration. We propose that up-regulation of the newly
      founded regeneration-associated gene tppp3 may enhance axonal regeneration.

PMID- 29209166
TI  - miR-145-5p/Nurr1/TNF-alpha Signaling-Induced Microglia Activation Regulates
      Neuron Injury of Acute Cerebral Ischemic/Reperfusion in Rats.
AB  - Nurr1 is a member of the nuclear receptor 4 family of orphan nuclear receptors
      that is decreased in inflammatory responses and leads to neurons death in
      Parkinson's disease. Abnormal expression of Nurr1 have been attributed to various
      signaling pathways, but little is known about microRNAs (miRNAs) regulation of
      Nurr1 in ischemia/reperfusion injury. To investigate the post transcriptional
      regulatory networks of Nurr1, we used a miRNA screening approach and identified
      miR-145-5p as a putative regulator of Nurr1. By using computer predictions, we
      identified and confirmed a miRNA recognition element in the 3'UTR of Nurr1 that
      was responsible for miR-145-5p-mediated suppression. We next demonstrated that
      overexpression of Nurr1 inhibited TNF-alpha expression in microglia by trans
      repression and finally attenuated ischemia/reperfusion-induced inflammatory and
      cytotoxic response of neurons. Results of further in vivo study revealed that
      anti-miR-145-5p administration brought about increasing expression of Nurr1 and
      reduction of infarct volume in acute cerebral ischemia. Administration of anti
      miR-145-5p promotes neurological outcome of rats post MCAO/R. It might be an
      effective therapeutic strategy to relieve neurons injury upon
      ischemia/reperfusion of rats through interrupting the axis signaling of miR-145
      5p- Nurr1-TNF-alpha in acute phase.

PMID- 29209167
TI  - Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses
      Interleukin-1beta-Mediated Neuroinflammation.
AB  - Neurodegenerative disorders and brain damage are initiated by excessive
      production of reactive oxygen species (ROS), which leads to tissue injury,
      cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase
      1 (HO-1) is an oxidative-sensor protein induced by ROS generation or carbon
      monoxide (CO) release. CO releasing molecules (CORMs), including CORM-3, exert
      anti-oxidant and anti-inflammatory effects. However, the molecular mechanisms of
      CORM-3-induced HO-1 expression and protection against interleukin (IL)-1beta
      induced inflammatory responses have not been fully elucidated in rat brain
      astrocytes (RBA-1). To study the regulation of CORM-3-induced HO-1 expression,
      signaling pathways, promoter activity, mRNA and protein expression were assessed
      following treatment with pharmacological inhibitors and gene-specific siRNA
      knockdown. We found that CORM-3 mediated HO-1 induction via transcritional and
      translational processes. Furthermore, CORM-3-induced HO-1 expression was mediated
      by phosphorylation of several protein kinases, such as c-Src, Pyk2, protein
      kinase Calpha (PKCalpha) and p42/p44 mitogen-activated protein kinase (MAPK),
      which were inhibited by respective pharmacological inhibitors or by gene-specific
      knockdown with siRNA transfections. Next, we found that CORM-3 sequentially
      activated the c-Src/Pyk2/PKCalpha/p42/p44 MAPK pathway, thereby up-regulating
      mRNA for the activator protein (AP)-1 components c-Jun and c-Fos; these effects
      were attenuated by an AP-1 inhibitor (Tanshinone IIA; TSIIA) and other relevant
      inhibitors. Moreover, CORM-3-induced upregulation of HO-1 attenuated the IL-1beta
      induced cell migration and matrix metallopeptidase-9 mRNA expression in RBA-1
      cells. These effects were reversed by an matrix metalloproteinase (MMP)2/9
      inhibitor or by transfection with HO-1 siRNA.

PMID- 29209168
TI  - Direct Neuronal Glucose Uptake Is Required for Contextual Fear Acquisition in the
      Dorsal Hippocampus.
AB  - The metabolism of glucose is a nearly exclusive source of energy for maintaining
      neuronal survival, synaptic transmission and information processing in the brain.
      Two glucose metabolism pathways have been reported, direct neuronal glucose
      uptake and the astrocyte-neuron lactate shuttle (ANLS), which can be involved in
      these functions simultaneously or separately. Although ANLS in the dorsal
      hippocampus (DH) has been proved to be required for memory consolidation, the
      specific metabolic pathway involved during memory acquisition remains unclear.
      The DH and amygdala are two key brain regions for acquisition of contextual fear
      conditioning (CFC). In 2-NBDG experiments, we observed that 2-NBDG-positive
      neurons were significantly increased during the acquisition of CFC in the DH.
      However, in the amygdala and cerebellum, 2-NBDG-positive neurons were not changed
      during CFC training. Strikingly, microinjection of a glucose transporter (GLUT)
      inhibitor into the DH decreased freezing values during CFC training and 1 h
      later, while injection of a monocarboxylate transporter (MCT) inhibitor into the
      amygdala also reduced freezing values. Therefore, we demonstrated that direct
      neuronal glucose uptake was the primary means of energy supply in the DH, while
      ANLS might supply energy in the amygdala during acquisition. Furthermore,
      knockdown of GLUT3 by a lentivirus in the DH impaired the acquisition of CFC.
      Taken together, the results indicated that there were two different glucose
      metabolism pathways in the DH and amygdala during acquisition of contextual fear
      memory and that direct neuronal glucose uptake in the DH may be regulated by
      GLUT3.

PMID- 29209169
TI  - Amyloid-beta Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and
      Cognitive Dysfunction in Multiple Sclerosis.
AB  - Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly
      involving processing speed and episodic memory. Both demyelination and gray
      matter atrophy can contribute to cognitive deficits in MS. In recent years,
      neuroinflammation is emerging as a new factor influencing clinical course in MS.
      Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity
      occurring within hippocampal structures is considered as one of the basic
      physiological mechanisms of learning and memory. In experimental models of MS,
      hippocampal plasticity is profoundly altered by proinflammatory cytokines.
      Although mechanisms of inflammation-induced hippocampal pathology in MS are not
      completely understood, alteration of Amyloid-beta (Abeta) metabolism is emerging
      as a key factor linking together inflammation, synaptic plasticity and
      neurodegeneration in different neurological diseases. We explored the correlation
      between concentrations of Abeta1-42 and the levels of some proinflammatory and
      anti-inflammatory cytokines (interleukin-1beta (IL-1beta), IL1-ra, IL-8, IL-10,
      IL-12, tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma)) in
      the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Abeta1
      42 were negatively correlated with the proinflammatory cytokine IL-8 and
      positively correlated with the anti-inflammatory molecules IL-10 and interleukin
      1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were
      either borderline or not significant. Our data show that an imbalance between
      proinflammatory and anti-inflammatory cytokines may lead to altered Abeta
      homeostasis, representing a key factor linking together inflammation, synaptic
      plasticity and cognitive dysfunction in MS. This could be relevant to identify
      novel therapeutic approaches to hinder the progression of cognitive dysfunction
      in MS.

PMID- 29209170
TI  - Noradrenaline Modulates the Membrane Potential and Holding Current of Medial
      Prefrontal Cortex Pyramidal Neurons via beta1-Adrenergic Receptors and HCN
      Channels.
AB  - The medial prefrontal cortex (mPFC) receives dense noradrenergic projections from
      the locus coeruleus. Adrenergic innervation of mPFC pyramidal neurons plays an
      essential role in both physiology (control of memory formation, attention,
      working memory, and cognitive behavior) and pathophysiology (attention deficit
      hyperactivity disorder, posttraumatic stress disorder, cognitive deterioration
      after traumatic brain injury, behavioral changes related to addiction,
      Alzheimer's disease and depression). The aim of this study was to elucidate the
      mechanism responsible for adrenergic receptor-mediated control of the resting
      membrane potential in layer V mPFC pyramidal neurons. The membrane potential or
      holding current of synaptically isolated layer V mPFC pyramidal neurons was
      recorded in perforated-patch and classical whole-cell configurations in slices
      from young rats. Application of noradrenaline (NA), a neurotransmitter with
      affinity for all types of adrenergic receptors, evoked depolarization or inward
      current in the tested neurons irrespective of whether the recordings were
      performed in the perforated-patch or classical whole-cell configuration. The
      effect of noradrenaline depended on beta1- and not alpha1- or alpha2-adrenergic
      receptor stimulation. Activation of beta1-adrenergic receptors led to an increase
      in inward Na+ current through hyperpolarization-activated cyclic nucleotide-gated
      (HCN) channels, which carry a mixed Na+/K+ current. The protein kinase A- and C-,
      glycogen synthase kinase-3beta- and tyrosine kinase-linked signaling pathways
      were not involved in the signal transduction between beta1-adrenergic receptors
      and HCN channels. The transduction system operated in a membrane-delimited
      fashion and involved the betagamma subunit of G-protein. Thus, noradrenaline
      controls the resting membrane potential and holding current in mPFC pyramidal
      neurons through beta1-adrenergic receptors, which in turn activate HCN channels
      via a signaling pathway involving the betagamma subunit.

PMID- 29209171
TI  - Influence of Mechanical Stimuli on Schwann Cell Biology.
AB  - Schwann cells are the glial cells of the peripheral nervous system (PNS). They
      insulate axons by forming a specialized extension of plasma membrane called the
      myelin sheath. The formation of myelin is essential for the rapid saltatory
      propagation of action potentials and to maintain the integrity of axons. Although
      both axonal and extracellular matrix (ECM) signals are necessary for myelination
      to occur, the cellular and molecular mechanisms regulating myelination continue
      to be elucidated. Schwann cells in peripheral nerves are physiologically exposed
      to mechanical stresses (i.e., tensile, compressive and shear strains), occurring
      during development, adulthood and injuries. In addition, there is a growing body
      of evidences that Schwann cells are sensitive to the stiffness of their
      environment. In this review, we detail the mechanical constraints of Schwann
      cells and peripheral nerves. We explore the regulation of Schwann cell signaling
      pathways in response to mechanical stimulation. Finally, we provide a
      comprehensive overview of the experimental studies addressing the mechanobiology
      of Schwann cells. Understanding which mechanical properties can interfere with
      the cellular and molecular biology of Schwann cell during development,
      myelination and following injuries opens new insights in the regulation of PNS
      development and treatment approaches in peripheral neuropathies.

PMID- 29209172
TI  - The Role of Netrin-1 in Improving Functional Recovery through Autophagy
      Stimulation Following Spinal Cord Injury in Rats.
AB  - Our previous findings indicated that treatment with Netrin-1 could improve
      functional recovery through the stimulation of autophagy, by activating the AMP
      activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling
      pathway in rats following spinal cord injury (SCI). However, the underlying
      mechanisms were not elucidated. The purpose of this study was to investigate the
      underlying mechanisms by which Netrin-1 promotes autophagy and improves
      functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats,
      we observed that the autophagic flux in neurons was impaired, as reflected by the
      accumulation of light chain 3-II (LC3-II)-positive and LC3-positive
      autophagosomes (APs), accompanied by the accumulation of the autophagic
      substrate, Sequestosome 1 (SQSTM1; also known as p62). Our results showed that
      treatment with Netrin-1 increases the levels of the lysosomal protease cathepsin
      D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1), through the
      regulation of the nuclear localization of Transcription factor EB (TFEB) via the
      AMPK/mTOR signaling pathway. In addition, this enhancement of lysosomal
      biogenesis correlated strongly with the restoration of autophagic flux,
      inhibition of neural apoptosis and improved functional recovery. Suppression of
      lysosomal biogenesis via the inhibition of the nuclear translocation of TFEB by
      Compound C abolished this restoration of autophagic flux and the functional
      recovery effects of Netrin-1 following SCI. Taken together, these results
      indicate that Netrin-1 enhances lysosomal biogenesis by regulating the nuclear
      translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, the
      enhancement of lysosomal biogenesis by Netrin-1 following SCI promotes autophagic
      flux and improves functional recovery in rats. Thus, the regulation of lysosomal
      biogenesis by modulating the nuclear localization of TFEB might be a novel
      approach for the treatment of SCI.

PMID- 29209175
TI  - Editorial: Biology of Brain Disorders.

PMID- 29209176
TI  - Central Projections of Antennal and Labial Palp Sensory Neurons in the Migratory
      Armyworm Mythimna separata.
AB  - The oriental armyworm, Mythimna separata (Walker), is a polyphagous, migratory
      pest relying on olfactory cues to find mates, locate nectar, and guide long
      distance flight behavior. In the present study, a combination of neuroanatomical
      techniques were utilized on this species, including backfills, confocal
      microscopy, and three-dimensional reconstructions, to trace the central
      projections of sensory neurons from the antenna and the labial pit organ,
      respectively. As previously shown, the axons of the labial sensory neurons
      project via the ipsilateral labial nerve and terminate in three main areas of the
      central nervous system: (1) the labial-palp pit organ glomerulus of each antennal
      lobe, (2) the gnathal ganglion, and (3) the prothoracic ganglion of the ventral
      nerve cord. Similarly, the antennal sensory axons project to multiple areas of
      the central nervous system. The ipsilateral antennal nerve targets mainly the
      antennal lobe, the antennal mechanosensory and motor center, and the prothoracic
      and mesothoracic ganglia. Specific staining experiments including dye application
      to each of the three antennal segments indicate that the antennal lobe receives
      input from flagellar olfactory neurons exclusively, while the antennal
      mechanosensory and motor center is innervated by mechanosensory neurons from the
      whole antenna, comprising the flagellum, pedicle, and scape. The terminals in the
      mechanosensory and motor center are organized in segregated zones relating to the
      origin of neurons. The flagellar mechanosensory axons target anterior zones,
      while the pedicular and scapal axons terminate in posterior zones. In the ventral
      nerve cord, the processes from the antennal sensory neurons terminate in the
      motor area of the thoracic ganglia, suggesting a close connection with motor
      neurons. Taken together, the numerous neuropils innervated by axons both from the
      antenna and labial palp indicate the multiple roles these sensory organs serve in
      insect behavior.

PMID- 29209174
TI  - Potential Mechanisms Underlying Inflammation-Enhanced Aminoglycoside-Induced
      Cochleotoxicity.
AB  - Aminoglycoside antibiotics remain widely used for urgent clinical treatment of
      life-threatening infections, despite the well-recognized risk of permanent
      hearing loss, i.e., cochleotoxicity. Recent studies show that aminoglycoside
      induced cochleotoxicity is exacerbated by bacteriogenic-induced inflammation.
      This implies that those with severe bacterial infections (that induce systemic
      inflammation), and are treated with bactericidal aminoglycosides are at greater
      risk of drug-induced hearing loss than previously recognized. Incorporating this
      novel comorbid factor into cochleotoxicity risk prediction models will better
      predict which individuals are more predisposed to drug-induced hearing loss.
      Here, we review the cellular and/or signaling mechanisms by which host-mediated
      inflammatory responses to infection could enhance the trafficking of systemically
      administered aminoglycosides into the cochlea to enhance the degree of
      cochleotoxicity over that in healthy preclinical models. Once verified, these
      mechanisms will be potential targets for novel pharmacotherapeutics that reduce
      the risk of drug-induced hearing loss (and acute kidney damage) without
      compromising the life-saving bactericidal efficacy of aminoglycosides.

PMID- 29209177
TI  - A New Behavioral Test and Associated Genetic Tools Highlight the Function of
      Ventral Abdominal Muscles in Adult Drosophila.
AB  - The function of the nervous system in complex animals is reflected by the
      achievement of specific behaviors. For years in Drosophila, both simple and
      complex behaviors have been studied and their genetic bases have emerged. The
      neuromuscular junction is maybe one of the prototypal simplest examples. A motor
      neuron establishes synaptic connections on its muscle cell target and elicits
      behavior: the muscle contraction. Different muscles in adult fly are related to
      specific behaviors. For example, the thoracic muscles are associated with flight
      and the leg muscles are associated with locomotion. However, specific tools are
      still lacking for the study of cellular physiology in distinct motor neuron
      subpopulations. Here we decided to use the abdominal muscles and in particular
      the ventral abdominal muscles (VAMs) in adult Drosophila as new model to link a
      precise behavior to specific motor neurons. Hence, we developed a new behavioral
      test based on the folding movement of the adult abdomen. Further, we performed a
      genetic screen and identify two specific Gal4 lines with restricted expression
      patterns to the adult motor neurons innervating the VAMs or their precursor
      cells. Using these genetic tools, we showed that the lack of the VAMs or the loss
      of the synaptic transmission in their innervating motor neurons lead to a
      significant impairment of the abdomen folding behavior. Altogether, our results
      allow establishing a direct link between specific motor neurons and muscles for
      the realization of particular behavior: the folding behavior of the abdomen in
      Drosophila.

PMID- 29209178
TI  - A Three-Layer Network Model of Direction Selective Circuits in the Optic Tectum.
AB  - The circuit mechanisms that give rise to direction selectivity in the retina have
      been studied extensively but how direction selectivity is established in
      retinorecipient areas of the brain is less well understood. Using functional
      imaging in larval zebrafish we examine how the direction of motion is encoded by
      populations of neurons at three layers of the optic tectum; retinal ganglion cell
      axons (RGCs), a layer of superficial inhibitory interneurons (SINs), and
      periventricular neurons (PVNs), which constitute the majority of neurons in the
      tectum. We show that the representation of motion direction is transformed at
      each layer. At the level of RGCs and SINs the direction of motion is encoded by
      three direction-selective (DS) subtypes tuned to upward, downward, and caudal-to
      rostral motion. However, the tuning of SINs is significantly narrower and this
      leads to a conspicuous gap in the representation of motion in the rostral-to
      caudal direction at the level of SINs. Consistent with previous findings we
      demonstrate that, at the level of PVNs the direction of motion is encoded by four
      DS cell types which include an additional DS PVN cell type tuned to rostral-to
      caudal motion. Strikingly, the tuning profile of this emergent cell type overlaps
      with the gap in the representation of rostral-to-caudal motion at the level of
      SINs. Using our functional imaging data we constructed a simple computational
      model that demonstrates how the emergent population of PVNs is generated by the
      interactions of cells at each layer of the tectal network. The model predicts
      that PVNs tuned to rostral-to-caudal motion can be generated via convergence of
      DS RGCs tuned to upward and downward motion and feedforward tuned inhibition via
      SINs which suppresses responses to non-preferred directions. Thus, by reshaping
      directional tuning that is inherited from the retina inhibitory inputs from SINs
      can generate a novel subtype of DS PVN and in so doing enhance the encoding of
      directional stimuli.

PMID- 29209173
TI  - Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic
      Plasticity.
AB  - Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a
      high prevalence and impact on society. ASDs are characterized by deficits in both
      social behavior and cognitive function. There is a strong genetic basis
      underlying ASDs that is highly heterogeneous; however, multiple studies have
      highlighted the involvement of key processes, including neurogenesis, neurite
      growth, synaptogenesis and synaptic plasticity in the pathophysiology of
      neurodevelopmental disorders. In this review article, we focus on the major genes
      and signaling pathways implicated in ASD and discuss the cellular, molecular and
      functional studies that have shed light on common dysregulated pathways using in
      vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has
      a prevalence of 1 in 68 children in the United States.ASDs are highly
      heterogeneous in their genetic basis.ASDs share common features at the cellular
      and molecular levels in the brain.Most ASD genes are implicated in neurogenesis,
      structural maturation, synaptogenesis and function.

PMID- 29209179
TI  - Effect of Transcranial Direct Current Stimulation of the Medial Prefrontal Cortex
      on the Gratitude of Individuals with Heterogeneous Ability in an Experimental
      Labor Market.
AB  - Gratitude is an important aspect of human sociality, which benefits mental health
      and interpersonal relationships. Thus, elucidating the neural mechanism of
      gratitude, which is only now beginning to be investigated, is important. To this
      end, this study specifies the medial prefrontal cortex (mPFC) involved in the
      gratitude of heterogeneous individuals using the transcranial direct current
      stimulation (tDCS) technique. Previous neural studies have shown the involvement
      of mPFC in social cognition and value evaluation, which are closely related to
      gratitude. However, the causal relationship between this neural area and
      gratitude has not been fully examined and the effect of individual social
      heterogeneity has been ignored. Meanwhile, behavioral economics studies have
      proposed that the abilities of employees in the labor market would affect their
      gratitude and emotional response. Thus, we designed an experiment based on gift
      exchange game to investigate the relationship between mPFC and gratitude of
      heterogeneous employees. Before the experiment, participants were asked to
      perform self-cognition of their abilities through an appropriately difficult
      task. We then used the effort of participants to imply their gratitude and
      analyzed the effort levels of employees with different abilities under anodal,
      cathodal, and sham stimulations. The results showed that employees under anodal
      stimulation were significantly likely to increase their effort than those under
      sham stimulation, and employees under cathodal stimulation ranked at the bottom
      of the list. Moreover, the effort levels of low-ability employees were obviously
      higher than those of high-ability employees. The cathodal stimulation of mPFC
      significantly reduced the effort levels of low-ability employees, whereas its
      anodal tDCS stimulation increased the effort levels of high-ability employees.
      These outcomes verify the relationship between mPFC and gratitude using tDCS and
      provided one of the first instances of neural evidence for the incentive
      mechanism design in the labor market to a certain extent.

PMID- 29209180
TI  - Frontal EEG Asymmetry of Mood: A Mini-Review.
AB  - The present mini-review was aimed at exploring the frontal EEG asymmetry of mood.
      With respect to emotion, interpreted as a discrete affective process, mood is
      more controllable, more nebulous, and more related to mind/cognition; in
      addition, causes are less well-defined than those eliciting emotion. Therefore,
      firstly, the rational for the distinction between emotion and mood was provided.
      Then, the main frontal EEG asymmetry models were presented, such as the
      motivational approach/withdrawal, valence/arousal, capability, and inhibition
      asymmetric models. Afterward, the frontal EEG asymmetry of mood was investigated
      following three research lines, that is considering studies involving different
      mood induction procedures, dispositional mood (positive and negative affect), and
      mood alterations in both healthy and clinical populations. In general, results
      were found to be contradictory, no model is unequivocally supported regardless
      the research line considered. Different methodological issues were raised, such
      as: the composition of samples used across studies, in particular, gender and age
      were found to be critical variables that should be better addressed in future
      studies; the importance of third variables that might mediate the relationship
      between frontal EEG asymmetries and mood, for example bodily states and hormonal
      responses; the role of cognition, namely the interplay between mood and executive
      functions. In light of these issues, future research directions were proposed.
      Amongst others, the need to explore the neural connectivity that underpins EEG
      asymmetries, and the need to include both positive and negative mood conditions
      in the experimental designs have been highlighted.

PMID- 29209181
TI  - The Agent Brain: A Review of Non-invasive Brain Stimulation Studies on Sensing
      Agency.
AB  - According to philosophy of mind and neuroscientific models, the sense of agency
      can be defined as the sense that I am the one that is generating an action and
      causing its effects. Such ability to sense ourselves as causal agents is critical
      for the definition of intentional behavior and is a primary root for human
      interaction skills. The present mini-review aims at discussing evidences from non
      invasive brain stimulation (NIBS) studies targeting functional correlates of
      different aspects of agency and evidences on the way stimulation techniques
      affect such core feature of human subjective experience. Clinical and brain
      imaging studies helped in defining a neural network mediating agency-related
      processes, which includes the dorsolateral prefrontal cortex (dlPFC), the
      cingulate cortex (CC), the supplementary and pre-supplementary motor areas (SMA
      and pre-SMA), the posterior parietal cortex (PPC) and its inferior regions and
      the cerebellum. However, while the plurality of those structures mirrors the
      complexity of the phenomenon, their actual roles with respect to different
      components of the experience of agency have been primarily explored via
      correlational techniques, without a clear evidence about their causal
      significance with respect to the integration of sensorimotor information,
      intentionalization, and action monitoring processes. Therefore, insights into the
      specific causal role of different cortical structures can be specified by using
      NIBS techniques, in order to provide improved understanding into the bases of our
      ability vs. inability to properly act in complex social contexts.

PMID- 29209182
TI  - Cognitive, Emotional, and Auto-Activation Dimensions of Apathy in Parkinson's
      Disease.
AB  - Apathy is one of the most frequent non-motor manifestations in Parkinson's
      disease (PD) that can lead to a whole range of deleterious outcomes. In 2006,
      Levy and Dubois proposed a model that distinguishes three different apathy
      aetiologies in PD divided into three subtypes of disrupted processing: "emotional
      affective," "cognitive," and "auto-activation." These three dimensions associated
      with dopamine depletion present in the pathology would lead to the emergence of
      apathy in PD. The aim of this mini-review was to describe and discuss studies
      that have explore links between apathy and the three subtypes of disrupted
      processing proposed by Levy and Dubois (2006) and as well as the links between
      these dimensions and dopamine depletion in Parkinson's disease. The lack of
      consensus regarding the emotional-affective correlates of apathy and the lack of
      evidence supporting the hypothesis of the auto-activation deficit, do not clearly
      confirm the validity of Levy and Dubois's model. Furthermore, the suggested
      association between dopaminergic depletion and apathy must also be clarified.

PMID- 29209183
TI  - Cognitive Flexibility Training: A Large-Scale Multimodal Adaptive Active-Control
      Intervention Study in Healthy Older Adults.
AB  - As aging is associated with cognitive decline, particularly in the executive
      functions, it is essential to effectively improve cognition in older adults.
      Online cognitive training is currently a popular, though controversial method.
      Although some changes seem possible in older adults through training, far
      transfer, and longitudinal maintenance are rarely seen. Based on previous
      literature we created a unique, state-of-the-art intervention study by
      incorporating frequent sessions and flexible, novel, adaptive training tasks,
      along with an active control group. We created a program called TAPASS (Training
      Project Amsterdam Seniors and Stroke), a randomized controlled trial. Healthy
      older adults (60-80 y.o.) were assigned to a frequent- (FS) or infrequent
      switching (IS) experimental condition or to the active control group and
      performed 58 half-hour sessions over the course of 12 weeks. Effects on executive
      functioning, processing- and psychomotor speed, planning, verbal long term
      memory, verbal fluency, and reasoning were measured on four time points before,
      during and after the training. Additionally, we examined the explorative question
      which individual aspects added to training benefit. Besides improvements on the
      training, we found significant time effects on multiple transfer tasks in all
      three groups that likely reflected retest effects. No training-specific
      improvements were detected, and we did not find evidence of additional benefits
      of individual characteristics. Judging from these results, the therapeutic value
      of using commercially available training games to train the aging brain is
      modest, though any apparent effects should be ascribed more to expectancy and
      motivation than to the elements in our training protocol. Our results emphasize
      the importance of using parallel tests as outcome measures for transfer and
      including both active and passive control conditions. Further investigation into
      different training methods is advised, including stimulating social interaction
      and the use of more variable, novel, group-based yet individual-adjusted
      exercises.

PMID- 29209184
TI  - Dynamics of Intersubject Brain Networks during Anxious Anticipation.
AB  - How do large-scale brain networks reorganize during the waxing and waning of
      anxious anticipation? Here, threat was dynamically modulated during human
      functional MRI as two circles slowly meandered on the screen; if they touched, an
      unpleasant shock was delivered. We employed intersubject correlation analysis,
      which allowed the investigation of network-level functional connectivity across
      brains, and sought to determine how network connectivity changed during periods
      of approach (circles moving closer) and periods of retreat (circles moving
      apart). Analysis of positive connection weights revealed that dynamic threat
      altered connectivity within and between the salience, executive, and task
      negative networks. For example, dynamic functional connectivity increased within
      the salience network during approach and decreased during retreat. The opposite
      pattern was found for the functional connectivity between the salience and task
      negative networks: decreases during approach and increases during approach.
      Functional connections between subcortical regions and the salience network also
      changed dynamically during approach and retreat periods. Subcortical regions
      exhibiting such changes included the putative periaqueductal gray, putative
      habenula, and putative bed nucleus of the stria terminalis. Additional analysis
      of negative functional connections revealed dynamic changes, too. For example,
      negative weights within the salience network decreased during approach and
      increased during retreat, opposite what was found for positive weights. Together,
      our findings unraveled dynamic features of functional connectivity of large-scale
      networks and subcortical regions across participants while threat levels varied
      continuously, and demonstrate the potential of characterizing emotional
      processing at the level of dynamic networks.

PMID- 29209185
TI  - Commentary: Brain-to-Brain Synchrony Tracks Real-World Dynamic Group Interactions
      in the Classroom and Cognitive Neuroscience: Synchronizing Brains in the
      Classroom.

PMID- 29209187
TI  - The Utility- and Use-of Neurotechnology to Recover Consciousness: Technical and
      Neuroethical Considerations in Approaching the "Hard Question" of Neuroscience.

PMID- 29209186
TI  - The Neural Association between Tendency to Forgive and Spontaneous Brain Activity
      in Healthy Young Adults.
AB  - The tendency to forgive (TTF) refers to one's global dispositional level of
      forgiveness across situations and relationships. Previous brain imaging studies
      examined activation patterns underlying forgiving process, yet the association
      between individual differences in the TTF and spontaneous brain activity at
      resting-state remains unknown. In this study, resting-state functional magnetic
      resonance imaging (fMRI) was used to investigate the correlation between the TTF
      and spontaneous brain activity in a young adult sample. Participants were 178
      young students (55 men) who completed the TTF scale and underwent a resting-state
      fMRI scan. Multiple regression analysis was conducted to assess the association
      between the regional amplitude of low-frequency fluctuations (ALFF) and TTF
      scores corrected for age and sex. Results showed that the ALFF value in the right
      dorsomedial prefrontal cortex (dmPFC), precuneus and inferior parietal lobule
      (IPL) were negatively associated with TTF scores. These findings suggest that the
      spontaneous brain activity of brain regions like the dmPFC, precuneus and IPL
      which are implicated in mentalizing and empathic response are associated with
      individual differences in the TTF.

PMID- 29209189
TI  - Spike-Triggered Regression for Synaptic Connectivity Reconstruction in Neuronal
      Networks.
AB  - How neurons are connected in the brain to perform computation is a key issue in
      neuroscience. Recently, the development of calcium imaging and multi-electrode
      array techniques have greatly enhanced our ability to measure the firing
      activities of neuronal populations at single cell level. Meanwhile, the
      intracellular recording technique is able to measure subthreshold voltage
      dynamics of a neuron. Our work addresses the issue of how to combine these
      measurements to reveal the underlying network structure. We propose the spike
      triggered regression (STR) method, which employs both the voltage trace and
      firing activity of the neuronal population to reconstruct the underlying synaptic
      connectivity. Our numerical study of the conductance-based integrate-and-fire
      neuronal network shows that only short data of 20 ~ 100 s is required for an
      accurate recovery of network topology as well as the corresponding coupling
      strength. Our method can yield an accurate reconstruction of a large neuronal
      network even in the case of dense connectivity and nearly synchronous dynamics,
      which many other network reconstruction methods cannot successfully handle. In
      addition, we point out that, for sparse networks, the STR method can infer
      coupling strength between each pair of neurons with high accuracy in the absence
      of the global information of all other neurons.

PMID- 29209188
TI  - Age-Related Decline of Wrist Position Sense and its Relationship to Specific
      Physical Training.
AB  - Perception of limb and body positions is known as proprioception. Sensory
      feedback, especially from proprioceptive receptors, is essential for motor
      control. Aging is associated with a decline in position sense at proximal joints,
      but there is inconclusive evidence of distal joints being equally affected by
      aging. In addition, there is initial evidence that physical activity attenuates
      age-related decline in proprioception. Our objectives were, first, to establish
      wrist proprioceptive acuity in a large group of seniors and compare their
      perception to young adults, and second, to determine if specific types of
      training or regular physical activity are associated with preserved wrist
      proprioception. We recruited community-dwelling seniors (n = 107, mean age, 70 +/
      5 years, range, 65-84 years) without cognitive decline (Mini Mental State
      Examination-brief version >=13/16) and young adult students (n = 51, mean age, 20
      +/- 1 years, range, 19-26 years). Participants performed contralateral and
      ipsilateral wrist position sense matching tasks with a bimanual wrist
      manipulandum to a 15 degrees  flexion reference position. Systematic error or
      proprioceptive bias was computed as the mean difference between matched and
      reference position. The respective standard deviation over five trials
      constituted a measure of random error or proprioceptive precision. Current levels
      of physical activity and previous sport, musical, or dance training were obtained
      through a questionnaire. We employed longitudinal mixed effects linear models to
      calculate the effects of trial number, sex, type of matching task and age on
      wrist proprioceptive bias and precision. The main results were that relative
      proprioceptive bias was greater in older when compared to young adults (mean
      difference: 36% ipsilateral, 88% contralateral, p < 0.01). Proprioceptive
      precision for contralateral but not for ipsilateral matching was smaller in older
      than in young adults (mean difference: 38% contralateral, p < 0.01). Longer years
      of dance training were associated with smaller bias during ipsilateral matching
      (p < 0.01). Other types of training or physical activity levels did not affect
      bias or precision. Our findings demonstrate that aging is associated with a
      decline in proprioceptive bias in distal arm joints, but age does not negatively
      affect proprioceptive precision. Further, specific types of long-term dance
      related training may attenuate age-related decline in proprioceptive bias.

PMID- 29209190
TI  - Classification of EEG Signals Based on Pattern Recognition Approach.
AB  - Feature extraction is an important step in the process of electroencephalogram
      (EEG) signal classification. The authors propose a "pattern recognition" approach
      that discriminates EEG signals recorded during different cognitive conditions.
      Wavelet based feature extraction such as, multi-resolution decompositions into
      detailed and approximate coefficients as well as relative wavelet energy were
      computed. Extracted relative wavelet energy features were normalized to zero mean
      and unit variance and then optimized using Fisher's discriminant ratio (FDR) and
      principal component analysis (PCA). A high density EEG dataset validated the
      proposed method (128-channels) by identifying two classifications: (1) EEG
      signals recorded during complex cognitive tasks using Raven's Advance Progressive
      Metric (RAPM) test; (2) EEG signals recorded during a baseline task (eyes open).
      Classifiers such as, K-nearest neighbors (KNN), Support Vector Machine (SVM),
      Multi-layer Perceptron (MLP), and Naive Bayes (NB) were then employed. Outcomes
      yielded 99.11% accuracy via SVM classifier for coefficient approximations (A5) of
      low frequencies ranging from 0 to 3.90 Hz. Accuracy rates for detailed
      coefficients were 98.57 and 98.39% for SVM and KNN, respectively; and for
      detailed coefficients (D5) deriving from the sub-band range (3.90-7.81 Hz).
      Accuracy rates for MLP and NB classifiers were comparable at 97.11-89.63% and
      91.60-81.07% for A5 and D5 coefficients, respectively. In addition, the proposed
      approach was also applied on public dataset for classification of two cognitive
      tasks and achieved comparable classification results, i.e., 93.33% accuracy with
      KNN. The proposed scheme yielded significantly higher classification performances
      using machine learning classifiers compared to extant quantitative feature
      extraction. These results suggest the proposed feature extraction method reliably
      classifies EEG signals recorded during cognitive tasks with a higher degree of
      accuracy.

PMID- 29209191
TI  - Conduction Delay Learning Model for Unsupervised and Supervised Classification of
      Spatio-Temporal Spike Patterns.
AB  - Precise spike timing is considered to play a fundamental role in communications
      and signal processing in biological neural networks. Understanding the mechanism
      of spike timing adjustment would deepen our understanding of biological systems
      and enable advanced engineering applications such as efficient computational
      architectures. However, the biological mechanisms that adjust and maintain spike
      timing remain unclear. Existing algorithms adopt a supervised approach, which
      adjusts the axonal conduction delay and synaptic efficacy until the spike timings
      approximate the desired timings. This study proposes a spike timing-dependent
      learning model that adjusts the axonal conduction delay and synaptic efficacy in
      both unsupervised and supervised manners. The proposed learning algorithm
      approximates the Expectation-Maximization algorithm, and classifies the input
      data encoded into spatio-temporal spike patterns. Even in the supervised
      classification, the algorithm requires no external spikes indicating the desired
      spike timings unlike existing algorithms. Furthermore, because the algorithm is
      consistent with biological models and hypotheses found in existing biological
      studies, it could capture the mechanism underlying biological delay learning.

PMID- 29209192
TI  - Response of Electrical Activity in an Improved Neuron Model under Electromagnetic
      Radiation and Noise.
AB  - Electrical activities are ubiquitous neuronal bioelectric phenomena, which have
      many different modes to encode the expression of biological information, and
      constitute the whole process of signal propagation between neurons. Therefore, we
      focus on the electrical activities of neurons, which is also causing widespread
      concern among neuroscientists. In this paper, we mainly investigate the
      electrical activities of the Morris-Lecar (M-L) model with electromagnetic
      radiation or Gaussian white noise, which can restore the authenticity of neurons
      in realistic neural network. First, we explore dynamical response of the whole
      system with electromagnetic induction (EMI) and Gaussian white noise. We find
      that there are slight differences in the discharge behaviors via comparing the
      response of original system with that of improved system, and electromagnetic
      induction can transform bursting or spiking state to quiescent state and vice
      versa. Furthermore, we research bursting transition mode and the corresponding
      periodic solution mechanism for the isolated neuron model with electromagnetic
      induction by using one-parameter and bi-parameters bifurcation analysis. Finally,
      we analyze the effects of Gaussian white noise on the original system and coupled
      system, which is conducive to understand the actual discharge properties of
      realistic neurons.

PMID- 29209193
TI  - Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in
      Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces.
AB  - This perspective paper faces the future of alternative treatments that take
      advantage of a social and cognitive approach with regards to pharmacological
      therapy of auditory verbal hallucinations (AVH) in patients with schizophrenia.
      AVH are the perception of voices in the absence of auditory stimulation and
      represents a severe mental health symptom. Virtual/augmented reality (VR/AR) and
      brain computer interfaces (BCI) are technologies that are growing more and more
      in different medical and psychological applications. Our position is that their
      combined use in computer-based therapies offers still unforeseen possibilities
      for the treatment of physical and mental disabilities. This is why, the paper
      expects that researchers and clinicians undergo a pathway toward human-avatar
      symbiosis for AVH by taking full advantage of new technologies. This outlook
      supposes to address challenging issues in the understanding of non
      pharmacological treatment of schizophrenia-related disorders and the exploitation
      of VR/AR and BCI to achieve a real human-avatar symbiosis.

PMID- 29209194
TI  - A Heavy Tailed Expectation Maximization Hidden Markov Random Field Model with
      Applications to Segmentation of MRI.
AB  - A wide range of segmentation approaches assumes that intensity histograms
      extracted from magnetic resonance images (MRI) have a distribution for each brain
      tissue that can be modeled by a Gaussian distribution or a mixture of them.
      Nevertheless, intensity histograms of White Matter and Gray Matter are not
      symmetric and they exhibit heavy tails. In this work, we present a hidden Markov
      random field model with expectation maximization (EM-HMRF) modeling the
      components using the alpha-stable distribution. The proposed model is a
      generalization of the widely used EM-HMRF algorithm with Gaussian distributions.
      We test the alpha-stable EM-HMRF model in synthetic data and brain MRI data. The
      proposed methodology presents two main advantages: Firstly, it is more robust to
      outliers. Secondly, we obtain similar results than using Gaussian when the
      Gaussian assumption holds. This approach is able to model the spatial dependence
      between neighboring voxels in tomographic brain MRI.

PMID- 29209195
TI  - The Patient Repository for EEG Data + Computational Tools (PRED+CT).
AB  - Electroencephalographic (EEG) recordings are thought to reflect the network-wide
      operations of canonical neural computations, making them a uniquely insightful
      measure of brain function. As evidence of these virtues, numerous candidate
      biomarkers of different psychiatric and neurological diseases have been advanced.
      Presumably, we would only need to apply powerful machine-learning methods to
      validate these ideas and provide novel clinical tools. Yet, the reality of this
      advancement is more complex: the scale of data required for robust and reliable
      identification of a clinical biomarker transcends the ability of any single
      laboratory. To surmount this logistical hurdle, collective action and transparent
      methods are required. Here we introduce the Patient Repository of EEG Data +
      Computational Tools (PRED+CT: predictsite.com). The ultimate goal of this project
      is to host a multitude of available tasks, patient datasets, and analytic tools,
      facilitating large-scale data mining. We hope that successful completion of this
      aim will lead to the development of novel EEG biomarkers for differentiating
      populations of neurological and psychiatric disorders.

PMID- 29209196
TI  - Commentary: Association Between Alendronate Use and Hip Fracture Risk in Older
      Patients Using Oral Prednisolone.

PMID- 29209198
TI  - Economic Cognitions Among Older Adults: Parental Socialization Predicts Financial
      Planning for Retirement.
AB  - Drawing on the model on financial planning for retirement (FPR), the aim of this
      work is to explore how parental economic socialization both directly and
      indirectly affects FPR through the mediation of financial literacy, financial
      planning decisions and financial management. Data from a sample of 280
      participants aged between 45 and 63 years were used. The results show that
      parental economic socialization directly and indirectly influences FPR. Moreover,
      parental economic behavior acts as a positive model for the development of
      financial literacy and skills and for decisions about FPR. All the variables
      increased the explained variance of FPR. Lastly, we discuss the process by which
      parental economic socialization is positively related to financial literacy and
      skills that impact on FPR, indicating some implications and future lines of
      research.

PMID- 29209197
TI  - Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between
      Functional and Structural Brain Connectome in Community-Living Elders.
AB  - Human brain is structurally and functionally asymmetrical and the asymmetries of
      brain phenotypes have been shown to change in normal aging. Recent advances in
      graph theoretical analysis have showed topological lateralization between
      hemispheric networks in the human brain throughout the lifespan. Nevertheless,
      apparent discrepancies of hemispheric asymmetry were reported between the
      structural and functional brain networks, indicating the potentially complex
      asymmetry patterns between structural and functional networks in aging
      population. In this study, using multimodal neuroimaging (resting-state fMRI and
      structural diffusion tensor imaging), we investigated the characteristics of
      hemispheric network topology in 76 (male/female = 15/61, age = 70.08 +/- 5.30
      years) community-dwelling older adults. Hemispheric functional and structural
      brain networks were obtained for each participant. Graph theoretical approaches
      were then employed to estimate the hemispheric topological properties. We found
      that the optimal small-world properties were preserved in both structural and
      functional hemispheric networks in older adults. Moreover, a leftward asymmetry
      in both global and local levels were observed in structural brain networks in
      comparison with a symmetric pattern in functional brain network, suggesting a
      dissociable process of hemispheric asymmetry between structural and functional
      connectome in healthy older adults. Finally, the scores of hemispheric asymmetry
      in both structural and functional networks were associated with behavioral
      performance in various cognitive domains. Taken together, these findings provide
      new insights into the lateralized nature of multimodal brain connectivity,
      highlight the potentially complex relationship between structural and functional
      brain network alterations, and augment our understanding of asymmetric structural
      and functional specializations in normal aging.

PMID- 29209199
TI  - Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain
      Entropy Mapping.
AB  - Alzheimer's disease (AD) is a frequently observed, irreversible brain function
      disorder among elderly individuals. Resting-state functional magnetic resonance
      imaging (rs-fMRI) has been introduced as an alternative approach to assessing
      brain functional abnormalities in AD patients. However, alterations in the brain
      rs-fMRI signal complexities in mild cognitive impairment (MCI) and AD patients
      remain unclear. Here, we described the novel application of permutation entropy
      (PE) to investigate the abnormal complexity of rs-fMRI signals in MCI and AD
      patients. The rs-fMRI signals of 30 normal controls (NCs), 33 early MCI (EMCI),
      32 late MCI (LMCI), and 29 AD patients were obtained from the Alzheimer's disease
      Neuroimaging Initiative (ADNI) database. After preprocessing, whole-brain entropy
      maps of the four groups were extracted and subjected to Gaussian smoothing. We
      performed a one-way analysis of variance (ANOVA) on the brain entropy maps of the
      four groups. The results after adjusting for age and sex differences together
      revealed that the patients with AD exhibited lower complexity than did the MCI
      and NC controls. We found five clusters that exhibited significant differences
      and were distributed primarily in the occipital, frontal, and temporal lobes. The
      average PE of the five clusters exhibited a decreasing trend from MCI to AD. The
      AD group exhibited the least complexity. Additionally, the average PE of the five
      clusters was significantly positively correlated with the Mini-Mental State
      Examination (MMSE) scores and significantly negatively correlated with Functional
      Assessment Questionnaire (FAQ) scores and global Clinical Dementia Rating (CDR)
      scores in the patient groups. Significant correlations were also found between
      the PE and regional homogeneity (ReHo) in the patient groups. These results
      indicated that declines in PE might be related to changes in regional functional
      homogeneity in AD. These findings suggested that complexity analyses using PE in
      rs-fMRI signals can provide important information about the fMRI characteristics
      of cognitive impairments in MCI and AD.

PMID- 29209200
TI  - Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison
      with the MoCA in a Normal Population.
AB  - Background: Smart Aging is a Serious games (SGs) platform in a 3D virtual
      environment in which users perform a set of screening tests that address various
      cognitive skills. The tests are structured as 5 tasks of activities of daily life
      in a familiar environment. The main goal of the present study is to compare a
      cognitive evaluation made with Smart Aging with those of a classic standardized
      screening test, the Montreal Cognitive Assessment (MoCA). Methods: One thousand
      one-hundred thirty-one healthy adults aged between 50 and 80 (M = 64.3 +/- 8.3)
      were enrolled in the study. They received a cognitive evaluation with the MoCA
      and the Smart Aging platform. Participants were grouped according to their MoCA
      global and specific cognitive domain (i.e., memory, executive functions, working
      memory, visual spatial elaboration, language, and orientation) scores and we
      explored differences among these groups in the Smart Aging indices. Results: One
      thousand eighty-six older adults (M = 64.0 +/- 8.0) successfully completed the
      study and were stratified according to their MoCA score: Group 1 with MoCA < 27
      (n = 360); Group 2 with 27 >= MoCA < 29 (n = 453); and Group 3 with MoCA >= 29 (n
      = 273). MoCA groups significantly differed in most of the Smart Aging indices
      considered, in particular as concerns accuracy (ps < 0.001) and time (ps < 0.001)
      for completing most of the platform tasks. Group 1 was outperformed by the other
      two Groups and was slower than them in these tasks, which were those supposed to
      assess memory and executive functions. In addition, significant differences
      across groups also emerged when considering the single cognitive domains of the
      MoCA and the corresponding performances in each Smart Aging task. In particular,
      this platform seems to be a good proxy for assessing memory, executive functions,
      working memory, and visual spatial processes. Conclusion: These findings
      demonstrate the validity of Smart Aging for assessing cognitive functions in
      normal aging. Future studies will validate this platform also in the clinical
      aging populations.

PMID- 29209202
TI  - Neural Basis of Enhanced Executive Function in Older Video Game Players: An fMRI
      Study.
AB  - Video games have been found to have positive influences on executive function in
      older adults; however, the underlying neural basis of the benefits from video
      games has been unclear. Adopting a task-based functional magnetic resonance
      imaging (fMRI) study targeted at the flanker task, the present study aims to
      explore the neural basis of the improved executive function in older adults with
      video game experiences. Twenty video game players (VGPs) and twenty non-video
      game players (NVGPs) of 60 years of age or older participated in the present
      study, and there are no significant differences in age (t = 0.62, p = 0.536),
      gender ratio (t = 1.29, p = 0.206) and years of education (t = 1.92, p = 0.062)
      between VGPs and NVGPs. The results show that older VGPs present significantly
      better behavioral performance than NVGPs. Older VGPs activate greater than NVGPs
      in brain regions, mainly in frontal-parietal areas, including the right
      dorsolateral prefrontal cortex, the left supramarginal gyrus, the right angular
      gyrus, the right precuneus and the left paracentral lobule. The present study
      reveals that video game experiences may have positive influences on older adults
      in behavioral performance and the underlying brain activation. These results
      imply the potential role that video games can play as an effective tool to
      improve cognitive ability in older adults.

PMID- 29209201
TI  - Do Lifestyle Activities Protect Against Cognitive Decline in Aging? A Review.
AB  - The number of patients suffering from dementia is expected to more than triple by
      the year 2040, and this represents a major challenge to publicly-funded
      healthcare systems throughout the world. One of the most effective prevention
      mechanisms against dementia lies in increasing brain- and cognitive-reserve
      capacity, which has been found to reduce the behavioral severity of dementia
      symptoms as neurological degeneration progresses. To date though, most of the
      factors known to enhance this reserve stem from largely immutable history
      factors, such as level of education and occupational attainment. Here, we review
      the potential for basic lifestyle activities, including physical exercise,
      meditation and musical experience, to contribute to reserve capacity and thus
      reduce the incidence of dementia in older adults. Relative to other therapies,
      these activities are low cost, are easily scalable and can be brought to market
      quickly and easily. Overall, although preliminary evidence is promising at the
      level of randomized control trials, the state of research on this topic remains
      underdeveloped. As a result, several important questions remain unanswered,
      including the amount of training required to receive any cognitive benefit from
      these activities and the extent to which this benefit continues following
      cessation. Future research directions are discussed for each lifestyle activity,
      as well as the potential for these and other lifestyle activities to serve as
      both a prophylactic and a therapeutic treatment for dementia.

PMID- 29209203
TI  - Linking Inter-Individual Variability in Functional Brain Connectivity to
      Cognitive Ability in Elderly Individuals.
AB  - Increasing evidence suggests that functional brain connectivity is an important
      determinant of cognitive aging. However, the fundamental concept of inter
      individual variations in functional connectivity in older individuals is not yet
      completely understood. It is essential to evaluate the extent to which inter
      individual variability in connectivity impacts cognitive performance at an older
      age. In the current study, we aimed to characterize individual variability of
      functional connectivity in the elderly and to examine its significance to
      individual cognition. We mapped inter-individual variability of functional
      connectivity by analyzing whole-brain functional connectivity magnetic resonance
      imaging data obtained from a large sample of cognitively normal older adults. Our
      results demonstrated a gradual increase in variability in primary regions of the
      visual, sensorimotor, and auditory networks to specific subcortical structures,
      particularly the hippocampal formation, and the prefrontal and parietal cortices,
      which largely constitute the default mode and fronto-parietal networks, to the
      cerebellum. Further, the inter-individual variability of the functional
      connectivity correlated significantly with the degree of cognitive relevance.
      Regions with greater connectivity variability demonstrated more connections that
      correlated with cognitive performance. These results also underscored the crucial
      function of the long-range and inter-network connections in individual cognition.
      Thus, individual connectivity-cognition variability mapping findings may provide
      important information for future research on cognitive aging and neurocognitive
      diseases.

PMID- 29209205
TI  - Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement
      of Dopamine and GABA Systems.
AB  - Tolerance to the analgesic effect of morphine is a major clinical problem which
      can be managed by co-administration of another drug. This study investigated the
      ability of propranolol to potentiate the antinociceptive action of morphine and
      the possible mechanisms underlying this effect. Antinociception was assessed in
      three nociceptive tests (thermal, hot plate), (visceral, acetic acid), and
      (inflammatory, formalin test) in mice and quantified by measuring the percent
      maximum possible effect, the percent inhibition of acetic acid-evoked writhing
      response, and the area under the curve values of number of flinches for treated
      mice, respectively. The study revealed that propranolol (0.25-20 mg/Kg, IP)
      administration did not produce analgesia in mice. However, 10 mg/Kg propranolol,
      enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1,
      and 2 mg/Kg, IP) in the three nociceptive tests. It also shifted the dose
      response curve of morphine to the left. The combined effect of propranolol and
      morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP),
      and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP). Repeated daily
      administration of propranolol (10 mg/Kg, IP) did not alter the nociceptive
      responses in the three pain tests, but it significantly potentiated morphine
      induced antinociception in the hot plate, acetic acid-evoked writhing, and in the
      second phase of formalin tests. Together, the data suggest that a cross-talk
      exists between the opioidergic and adrenergic systems and implicate dopamine and
      GABA systems in this synergistic effect of morphine-propranolol combination.
      Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid
      analgesics.

PMID- 29209204
TI  - Reward Circuitry Plasticity in Pain Perception and Modulation.
AB  - Although pain is a widely known phenomenon and an important clinical symptom that
      occurs in numerous diseases, its mechanisms are still barely understood. Owing to
      the scarce information concerning its pathophysiology, particularly what is
      involved in the transition from an acute state to a chronic condition, pain
      treatment is frequently unsatisfactory, therefore contributing to the
      amplification of the chronic pain burden. In fact, pain is an extremely complex
      experience that demands the recruitment of an intricate set of central nervous
      system components. This includes cortical and subcortical areas involved in
      interpretation of the general characteristics of noxious stimuli. It also
      comprises neural circuits that process the motivational-affective dimension of
      pain. Hence, the reward circuitry represents a vital element for pain experience
      and modulation. This review article focuses on the interpretation of the
      extensive data available connecting the major components of the reward circuitry
      to pain suffering, including the nucleus accumbens, ventral tegmental area, and
      the medial prefrontal cortex; with especial attention dedicated to the evaluation
      of neuroplastic changes affecting these structures found in chronic pain
      syndromes, such as migraine, trigeminal neuropathic pain, chronic back pain, and
      fibromyalgia.

PMID- 29209206
TI  - Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor
      Efficacy of Hypocrellin A.
AB  - Photodynamic therapy (PDT) has emerged as a potent novel therapeutic modality
      that induces cell death through light-induced activation of photosensitizer. But
      some photosensitizers have characteristics of poor water-solubility and non
      specific tissue distribution. These characteristics become main obstacles of PDT.
      In this paper, we synthesized a targeting drug delivery system (TDDS) to improve
      the water-solubility of photosensitizer and enhance the ability of targeted TFR
      positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co
      glycolide (PLGA) and carboxymethyl chitosan (CMC) nanoparticle loaded with a
      photosensitizer hypocrellin A (HA), named TF-HA-CMC-PLGA NPs. Morphology, size
      distribution, Fourier transform infrared (FT-IR) spectra, encapsulation
      efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In
      vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo
      cytotoxicity with strong reactive oxygen species (ROS) generation and apoptotic
      cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs
      was investigated with an A549 (TFR positive) tumor-bearing model in male athymic
      nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor
      inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and
      slight side effects in normal organs were observed. The results indicated that
      TDDS has great potential to enhance PDT therapeutic efficacy.

PMID- 29209207
TI  - Antiepileptic and Neuroprotective Effects of Oleamide in Rat Striatum on Kainate
      Induced Behavioral Seizure and Excitotoxic Damage via Calpain Inhibition.
AB  - Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to
      have wide range of neuropharmacological effects upon different neurochemical
      systems. However, the effects of oleamide on brain damage have scarcely been
      studied, and the molecular mechanisms and sites of its action remain elusive.
      Kainic acid (KA) has been used to produce an epileptic animal model that mimics
      human temporal lobe epilepsy and to induce calpain-activated excitotoxicity,
      which occurs in numerous neurodegenerative disorders. In this study, we examined
      whether oleamide protects against the KA-induced excitotoxic brain damage
      accompanied by behavioral seizure activity and neuronal cell death. Moreover,
      whether these effects of oleamide were mediated by calpain activity-related
      cellular mechanisms was investigated. KA-induced epileptic rats were produced by
      an intrastriatal injection of KA (5 nmole). Oral administration of oleamide (0.5,
      2, and 10 mg/kg) 30 min prior to the KA injection showed dose-dependent
      inhibition of the KA-induced behavioral seizure activities that were monitored
      starting from 60 to 180 min post-surgery. Further repetitive oral administration
      of oleamide (once per day) for the next 4 consecutive days post-KA injection
      produced significant neuroprotection against the disrupted neuronal integrity
      that resulted from KA-induced excitotoxic damage that was also demonstrated by
      staining of striatal tissue sections with cresyl violet, hematoxylin/eosin, and
      fluoro-Jade B. In addition, oleamide blocked the KA-induced cleavage of cyclin
      dependent kinase-5 coactivator (Cdk5-p35) and collapsin response mediator protein
      2, which are believed to be mediated by calpain activation in striatal tissues
      dissected from KA-induced epileptic rats. Oleamide also reversed the KA-induced
      reduction in expression of an endogenous calpain inhibitory protein, calpastatin,
      and a marker of synaptic activity, synapsin-II. The hypothesis that oleamide
      could induce direct calpain inhibition was further investigated using in vitro
      calpain assays in both brain tissue and a cell-free and calpain-overexpressed
      neuronal cell system. These findings together suggest that oleamide has
      protective effects against excitotoxicity-induced neuronal death and behavioral
      seizure, partly via its direct calpain inhibitory activity.

PMID- 29209208
TI  - The Clinical Pharmacokinetics and Pharmacodynamics of Warfarin When Combined with
      Compound Danshen: A Case Study for Combined Treatment of Coronary Heart Diseases
      with Atrial Fibrillation.
AB  - Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able
      to promote blood circulation. The combination might produce a synergic effect for
      patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether
      the combination increases the bleeding risk of warfarin is unclear, so the
      effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and
      pharmacodynamics (PD) profiles of warfarin was investigated in patients. The dose
      and blood concentrations of warfarin, the four indicators of blood coagulation,
      prothrombin time, activated partial thromboplatin time, thrombin time,
      fibrinogen, and international normalized ratio value were compared when with and
      without CDDP treatment. The population PK (PPK) and PPK-PD models were
      established to assess patient demographics, genetic polymorphisms and CDDP as
      covariates. And the Seattle Angina Questionnaire was used to evaluate clinical
      efficacy, and the bleeding risk of combination was analyzed. The results
      indicated that CDDP had little influence on PK and PD profiles of warfarin in
      most patients and the combination of CCDP and warfarin would be a promising
      alternative regime for CHD with AF patients. The study was registered on China
      Clinical Trial Registry with number ChiCTR-ONRC-13003523.

PMID- 29209210
TI  - Critical Role of Hepatic Cyp450s in the Testis-Specific Toxicity of (5R)-5
      Hydroxytriptolide in C57BL/6 Mice.
AB  - Low solubility, tissue accumulation, and toxicity are chief obstacles to
      developing triptolide derivatives, so a better understanding of the
      pharmacokinetics and toxicity of triptolide derivatives will help with these
      limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5
      hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a
      conditional knockout (KO) mouse model with liver-specific deletion of CYP450
      reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice
      suffered severe testicular toxicity (decreased testicular weight, spermatocytes
      apoptosis) unlike WT mice. Moreover, KO mice had greater LLDT-8 exposure as
      confirmed with elevated AUC and Cmax, increased drug half-life, and greater
      tissue distribution. gamma-H2AX, a marker of meiosis process, its localization
      and protein level in testis showed a distinct meiosis block induced by LLDT-8.
      RNA polymerase II (Pol II), an essential factor for RNA storage and synapsis in
      spermatogenesis, decreased in testes of KO mice after LLDT-8 treatment. Germ-cell
      line based assays confirmed that LLDT-8 selectively inhibited Pol II in
      spermatocyte-like cells. Importantly, the analysis of androgen receptor (AR)
      related genes showed that LLDT-8 did not change AR-related signaling in testes.
      Thus, hepatic CYP450s were responsible for in vivo metabolism and clearance of
      LLDT-8 and aggravated testicular injury may be due to increased LLDT-8 exposure
      in testis and subsequent Pol II reduction.

PMID- 29209209
TI  - Nonribosomal Peptides from Marine Microbes and Their Antimicrobial and Anticancer
      Potential.
AB  - Marine environments are largely unexplored and can be a source of new molecules
      for the treatment of many diseases such as malaria, cancer, tuberculosis, HIV
      etc. The Marine environment is one of the untapped bioresource of getting
      pharmacologically active nonribosomal peptides (NRPs). Bioprospecting of marine
      microbes have achieved many remarkable milestones in pharmaceutics. Till date,
      more than 50% of drugs which are in clinical use belong to the nonribosomal
      peptide or mixed polyketide-nonribosomal peptide families of natural products
      isolated from marine bacteria, cyanobacteria and fungi. In recent years large
      numbers of nonribosomal have been discovered from marine microbes using multi
      disciplinary approaches. The present review covers the NRPs discovered from
      marine microbes and their pharmacological potential along with role of genomics,
      proteomics and bioinformatics in discovery and development of nonribosomal
      peptides drugs.

PMID- 29209212
TI  - Identification of Antibody and Small Molecule Antagonists of Ferroportin-Hepcidin
      Interaction.
AB  - The iron exporter ferroportin and its ligand, the hormone hepcidin, control
      fluxes of stored and recycled iron for use in a variety of essential biochemical
      processes. Inflammatory disorders and malignancies are often associated with high
      hepcidin levels, leading to ferroportin down-regulation, iron sequestration in
      tissue macrophages and subsequent anemia. The objective of this research was to
      develop reagents to characterize the expression of ferroportin, the interaction
      between ferroportin and hepcidin, as well as to identify novel ferroportin
      antagonists capable of maintaining iron export in the presence of hepcidin.
      Development of investigative tools that enabled cell-based screening assays is
      described in detail, including specific and sensitive monoclonal antibodies that
      detect endogenously-expressed human and mouse ferroportin and fluorescently
      labeled chemically-synthesized human hepcidin. Large and small molecule
      antagonists inhibiting hepcidin-mediated ferroportin internalization were
      identified, and unique insights into the requirements for interaction between
      these two key iron homeostasis molecules are provided.

PMID- 29209211
TI  - Diabetes Mellitus and Alzheimer's Disease: The Protection of Epigallocatechin-3
      gallate in Streptozotocin Injection-Induced Models.
AB  - Diabetes mellitus is considered as a risk factor of Alzheimer's disease (AD), the
      front runner of neurodegenerative disorders. Streptozotocin (STZ) is a toxin for
      pancreatic beta-cell, which can construct a model of insulin deficient diabetes
      through intraperitoneal or intravenous injection. A model generated by
      intracerebroventricular STZ (icv-STZ) also shows numerous aspects of sporadic AD.
      The protective roles of tea polyphenols epigallocatechin-3-gallate (EGCG) on both
      two diseases were researched by some scientists. This review highlights the link
      between diabetes and AD and recent studies on STZ injection-induced models, and
      also discusses the protection of EGCG to clarify its treatment in STZ-induced
      diabetes and AD.

PMID- 29209213
TI  - Traditional and Current Food Use of Wild Plants Listed in the Russian
      Pharmacopoeia.
AB  - Historically Russia can be regarded as a "herbophilious" society. For centuries
      the multinational population of Russia has used plants in daily diet and for self
      medication. The specificity of dietary uptake of medicinal plants (especially
      those in the unique and highly developed Russian herbal medical tradition) has
      remained mostly unknown in other regions. Based on 11th edition of the State
      Pharmacopoeia of the USSR, we selected 70 wild plant species which have been used
      in food by local Russian populations. Empirical searches were conducted via the
      Russian-wide applied online database E-library.ru, library catalogs of public
      libraries in St-Petersburg, the databases Scopus, Web of Science, PubMed, and
      search engine Google Scholar. The large majority of species included in Russian
      Pharmacopoeia are used as food by local population, however, aerial parts are
      more widely used for food. In this review, we summarize data on medicinal species
      published in Russia and other countries that are included in the Russian
      Pharmacopoeia and have being used in food for a long time. Consequently, the
      Russian Pharmacopoeia is an important source of information on plant species used
      traditionally at the interface of food and medicine. At the same time, there are
      the so-called "functional foods", which denotes foods that not only serves to
      provide nutrition but also can be a source for prevention and cure of various
      diseases. This review highlights the potential of wild species of Russia
      monographed in its pharmacopeia for further developing new functional foods and
      through the lens of their incorporation into the pharmacopeia-showcases the
      species' importance in Russia.

PMID- 29209214
TI  - Fatal and Near-Fatal Non-allergic Reactions in Patients with Underlying Cardiac
      Disease Receiving Benzathine Penicillin G in Israel and Switzerland.
AB  - Benzathine Penicillin G (BPG) is commonly used for treatment of penicillin
      susceptible infections and secondary prevention of rheumatic fever. Death
      following administration of BPG is extremely rare-only a handful of cases have
      been described in the literature since the 1950's. In this case series from
      Israel and Switzerland, we describe nine cases of serious adverse reactions-six
      fatal reactions and three near-fatalities-occurring within minutes of receiving
      intramuscular BPG. Allergic reactions or faulty administration were not
      implicated in any of the cases; however, all patients had cardiac risk factors.
      This case series describes a relatively rare risk that should be borne in mind
      when prescribing BPG.

PMID- 29209215
TI  - Preparation, Evaluation and Bioavailability Studies of Eudragit Coated PLGA
      Nanoparticles for Sustained Release of Eluxadoline for the Treatment of Irritable
      Bowel Syndrome.
AB  - Eluxadoline is a newly approved orally administered drug used for the treatment
      of Irritable Bowel Syndrome with Diarrhea. It is reported as a poorly water
      soluble drug due to which its dissolution rate and oral bioavailability are very
      poor. In this work, various plain PLGA nanoparticles (NPs) (F1-F4) were prepared
      and optimized based on particle size, PDI, zeta potential and percent drug
      entrapment efficiency (EE). The developed plain NPs (F1-F4) showed average
      particle size ranging from 260.19 to 279.76 nm with smooth surface and EE of
      17.83-56.29%. The optimized plain NPs (F3) had particle size of 273.76 +/- 7.25
      nm with a low PDI value 0.327, zeta potential - 30.63 +/- 2.47 mV and % EE of
      56.29 +/- 2.56%. The optimized F3 NPs was further submitted for enteric coating
      using Eudragit S100 polymer and evaluated in terms of particles characterization,
      in vitro release and pharmacokinetic studies in rats. The bioavailability of
      plain and coated nanaoparticles were enhanced by 6.8- and 18.5-fold,
      respectively, compared to normal suspension. These results revealed that the
      developed coated NPs could be used for its oral delivery for an effective
      treatment of Irritable Bowel Syndrome with Diarrhea.

PMID- 29209216
TI  - Effects of Intensive Control of Glycemia on Clinical Kidney Outcomes in Type 2
      Diabetes Patients Compared with Standard Control: A Meta-Analysis.
AB  - Background: Association between poor control of glycemia and the onset of
      microvascular complications in type 2 diabetes mellitus (T2DM) patients is a hard
      issue. However, it seems that the impact of pharmacological treatment is
      important only in early stages of diabetic nephropathy. We sought to examine
      whether intensive glycemic control is associated with improvement of clinical
      Chronic Kidney Disease (CKD) outcomes compared to standard glycemic control.
      Methods: Meta-analysis of published and unpublished randomized controlled trials
      (RCT) and post-hoc analysis of RCTs comparing anti-diabetic drugs and/or insulin
      (intensive control) vs. dietary measures (standard control) for relevant outcomes
      related to progression of CKD clinically manifest was undertaken. Summary
      estimates obtained by random effects model and funnel plots for assessing
      reporting bias are presented. Results: Our analysis was based on four RCTs
      representing 27,391 adult T2DM patients with CKD from around the world. The
      pooled OR for the outcomes of doubling of serum creatinine and need of dialysis
      were, respectively, of 0.98 with 95% confidence interval (95% CI) 0.81-1.19, and
      0.84 with 95% CI 0.69-1.02. The pooled OR for the outcome of death from kidney
      failure was 0.62 with 95% CI 0.39-0.98. Clinical differences between studies were
      not translated in statistical heterogeneity. Reporting bias may be present.
      Conclusions: Intensive glycemic control has an effect on death from kidney
      failure compared to standard glycemic control. Better comprehension of glycemic
      control effects on both T2DM patients with and without CKD is important for
      individualization of these two treatment modalities.

PMID- 29209217
TI  - Arylacetamide Deacetylase Is Involved in Vicagrel Bioactivation in Humans.
AB  - Vicagrel, a structural analog of clopidogrel, is now being developed as a
      thienopyridine antiplatelet agent in a phase II clinical trial in China. Some
      studies have shown that vicagrel undergoes complete first-pass metabolism in
      human intestine, generating the hydrolytic metabolite 2-oxo-clopidogrel via
      carboxylesterase-2 (CES2) and subsequently the active metabolite H4 via CYP450s.
      This study aimed to identify hydrolases other than CES2 that are involved in the
      bioactivation of vicagrel in human intestine. This study is the first to
      determine that human arylacetamide deacetylase (AADAC) is involved in 2-oxo
      clopidogrel production from vicagrel in human intestine. In vitro hydrolytic
      kinetics were determined in human intestine microsomes and recombinant human CES
      and AADAC. The calculated contribution of CES2 and AADAC to vicagrel hydrolysis
      was 44.2 and 53.1% in human intestine, respectively. The AADAC-selective
      inhibitors vinblastine and eserine effectively inhibited vicagrel hydrolysis in
      vitro. In addition to CES2, human intestine AADAC was involved in vicagrel
      hydrolytic activation before it entered systemic circulation. In addition,
      simvastatin efficiently inhibited the production of both 2-oxo-clopidogrel and
      active H4; further clinical trials are needed to determine whether the hydrolytic
      activation of vicagrel is influenced by coadministration with simvastatin. This
      study deepens the understanding of the bioactivation and metabolism properties of
      vicagrel in humans, which can help further understand the bioactivation mechanism
      of vicagrel and the variations in the treatment responses to vicagrel and
      clopidogrel.

PMID- 29209218
TI  - Nootropic and Neuroprotective Effects of Dichrocephala integrifolia on
      Scopolamine Mouse Model of Alzheimer's Disease.
AB  - Alzheimer's disease the most common form of dementia in the elderly is a
      neurodegenerative disease that affects 44 millions of people worldwide. The first
      treatments against Alzheimer's disease are acetylcholinesterase inhibitors;
      however, these medications are associated with many side effects. Dichrocephala
      integrifolia is a traditional herb widely used by indigenous population of
      Cameroon to treat and prevent Alzheimer's disease and for memory improvement. In
      this study, we evaluated the effect of the decoction prepared from leaves of D.
      integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of
      six animals were used. The first two groups received distilled water for the
      distilled water and scopolamine groups. The four test groups received one of the
      four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and
      the positive control group received tacrine (10 mg/kg), a cholinesterase
      inhibitor used in the treatment of Alzheimer's disease, during 10 consecutive
      days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min
      after treatments, was used to induce memory impairment to all groups except the
      distilled water group on day 10 of drug treatment. The behavioral paradigms used
      to evaluate the effects of the treatment were the elevated plus maze for learning
      and memory, Y maze for spatial short-term memory, the novel object recognition
      for recognition memory and Morris water maze for the evaluation of spatial long
      term memory. After behavioral tests, animals were sacrificed and brains of a
      subset were used for the assessment of some biomarkers of oxidative stress
      (malondialdehyde and reduced glutathione levels) and for the evaluation of the
      acetylcholinesterase activity. From the remaining subset brains,
      histopathological analysis was performed. The results of this study showed that,
      D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01)
      improved spatial short-term and long-term memory, by increasing the percentage of
      spontaneous alternation in the Y maze and reducing the escape latency in the
      Morris water maze. Furthermore, the results of histopathological evaluation
      showed that D. integrifolia attenuated the neuronal death in the hippocampus
      induced by scopolamine. The main finding of this work is that D. integrifolia
      improves learning capacities and counteracts the memory impairment induced by
      scopolamine. Thus, D. integrifolia can be a promising plant resource for the
      management of Alzheimer's disease and memory loss.

PMID- 29209219
TI  - Differential Effects of Inhibitor Combinations on Lysophosphatidic Acid-Mediated
      Chemokine Secretion in Unprimed and Tumor Necrosis Factor-alpha-Primed Synovial
      Fibroblasts.
AB  - Lysophosphatidic acid (LPA) is a pleiotropic bioactive lysophospholipid involved
      in inflammatory mediator synthesis. Signaling through p38MAPK, ERK, Rho kinase,
      and MSK-CREB contributes to LPA-mediated IL-8 production in fibroblast-like
      synoviocytes (FLS) from rheumatoid arthritis (RA) patients. The study was
      undertaken to investigate how LPA activates MSKs and how signaling crosstalk
      between TNFalpha and LPA contributes to the super-production of
      cytokines/chemokines. RAFLS pretreated or not with TNFalpha were stimulated with
      LPA. Immunoblotting with phospho-antibodies monitored MSK activation.
      Cytokine/chemokine production was measured using ELISA and multiplex
      immunoassays. LPA induced MSK activation by signaling through ERK whereas
      p38MAPK, Rho kinase, NF-kappaB or PI3K contribute to IL-8 synthesis mainly via
      MSK-independent pathways. Priming with TNFalpha enhanced LPA-mediated MSK
      phosphorylation and cytokine/chemokine production. After priming with TNFalpha,
      inhibition of ERK or MSK failed to attenuate LPA-mediated IL-8 synthesis even if
      the MSK-CREB signaling axis was completely or partially inhibited. In TNFalpha
      primed cells, inhibition of LPA-mediated cytokine/chemokine synthesis required a
      specific combination of inhibitors such as p38MAPK and ERK for IL-8 and IL-6, and
      Rho kinase and NF-kappaB for MCP-1. The ability of the signaling inhibitors to
      block LPA induced cytokine/chemokine synthesis is dependent on the inflammatory
      cytokinic environment. In TNFalpha-primed RAFLS the super-production of IL-8 and
      IL-6 induced by LPA occurs mainly via MSK-independent pathways, and simultaneous
      inhibition of at least two MAPK signaling pathways was required to block their
      synthesis. Since simultaneous inhibition of both the p38MAPK and ERK-MSK-CREB
      pathways are required to significantly reduce LPA-mediated IL-8 and IL-6
      production in TNFalpha-preconditioned RAFLS, drug combinations targeting these
      two pathways are potential new strategies to treat rheumatoid arthritis.

PMID- 29209220
TI  - The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth
      Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation
      of CREB.
AB  - Hachimijiogan (HJG) is a traditional herbal medicine that improves anxiety
      disorders in patients with dementia. In this study, we tested the hypothesis that
      HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in
      Alzheimer disease (AD) model rats. First, we describe that HJG acts to induce
      neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line) like nerve
      growth factor (NGF) in a concentration-dependent manner (3 MUg/ml HJG, p < 0.05;
      10-500 MUg/ml HJG, p < 0.001). While six herbal constituents of HJG, Rehmannia
      root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and
      Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest
      with HJG (500 MUg/ml). Second, we demonstrated that HJG-induced neurite outgrowth
      was blocked by an inhibitor of cAMP response element binding protein (CREB), KG
      501 (10 MUM, p < 0.001). Moreover, HJG was observed to induce CREB
      phosphorylation 20-90 min after treatment (20 min, 2.50 +/- 0.58-fold) and CRE
      mediated transcription in cultured PC12 cells (500 MUg/ml, p < 0.01; 1000 MUg/ml,
      p < 0.001). These results suggest a CREB-dependent mechanism underlies the
      neurotrophic effects of HJG. Finally, we examined improvements of memory
      impairment following HJG treatment using a Morris water maze in AD model animals
      (CI + Abeta rats). Repeated oral administration of HJG improved memory impairment
      (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001) and induced CREB phosphorylation
      within the hippocampus (1000 mg/kg, p < 0.01). Together, our results suggest that
      HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate
      cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG
      could potentially be a substitute for neurotrophic factors as a treatment for
      dementia.

PMID- 29209221
TI  - Commentary: Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A
      Pharmacological, Biochemical and Behavioral Approach.

PMID- 29209222
TI  - PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs.
AB  - Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for
      respiratory diseases. Here we aimed to evaluate the ex vivo activity of
      marbofloxacin against Streptococcus suis in pig serum, as well as the optimal
      dosages scheme for avoiding the fluoroquinolone resistance development. A single
      dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and
      serum samples were collected during the next 72 h. Serum marbofloxacin content
      was determined by high-performance liquid chromatography. We estimated the Cmax
      (6.28 MUg/ml), AUC0-24 h (60.30 MUg.h/ml), AUC0-infinity (88.94 MUg.h/ml),
      T1/2ke, (12.48 h), Tmax (0.75 h) and Clb (0.104 L/h) of marbofloxacin in pigs, as
      well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral
      administration. We also determined the pharmacodynamic of marbofloxacin against
      134 Streptococcus suis strains isolated from Chinese cities in TSB and serum.
      These isolated strains had a MIC90 of 1 MUg/ml. HB2, a virulent, serotype 2
      isolate of SS, was selected for having antibacterial activity in TSB and serum to
      marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 MUg/ml
      in TSB, 2 MUg/ml in serum), minimum bactericidal concentration (MBC, 4 MUg/ml in
      TSB, 4 MUg/ml in serum), and mutant prevention concentration (2.56 MUg/ml in TSB)
      for marbofloxacin against Streptococcus suis (HB2). In serum, by inhibitory
      sigmoid Emax modeling, the AUC0-24h/MIC values for marbofloxacin against HB2 were
      25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on
      Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing
      Streptococcus suis were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36
      (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16
      (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a
      90% target attainment ratio. The data presented here provides optimized dosage
      information for clinical use; however, these predicted dosages should also be
      validated in clinical practice.

PMID- 29209223
TI  - Timing Strategies of Direct-Acting Antivirals and Biologics Administration in HCV
      Infected Subjects with Inflammatory Bowel Diseases.
AB  - Background: In the last years, inflammatory bowel disease (IBD) and hepatitis C
      virus (HCV) infection management has completely changed. However, the role of
      direct-acting antivirals (DAAs) and the correct timing of antiviral drugs
      administration in IBD patients needing biologics has not been evaluated.
      Objective: To discuss the management of HCV-infected IBD patients, focusing our
      attention on the timing of DAAs administration subjects needing biologics.
      Methods: Relevant articles addressing HCV management in patients needing
      biologics were identified by searching from PubMed, MEDLINE and Scopus. Results:
      Three possible timing strategies were identified: (1) sequential strategy,
      meaning the choice of treating firstly the active IBD with biologics and then,
      once the acute phase has been controlled, treating the HCV infection; (2)
      concomitant strategy, that is the contemporaneous beginning of DAAs and biologics
      administration; (3) inverted sequential strategy-the administration of antiviral
      therapy before biologics in HCV-infected IBD patients. The potential
      pharmacological interactions between biologics and DAAs have also been reported.
      Conclusions: Clinical management of HCV-infected IBD patients remains a
      challenging problem for clinicians, especially in terms of timing choice. Recent
      published data about DAAs are very encouraging also in IBD patients. All
      strategies could be considered safe and effective. However, further data are
      immediately required in order to evaluate hepatic toxicity of novel
      immunosuppressive drugs in IBD.

PMID- 29209224
TI  - Na+/H+ Exchanger 3 Is Expressed in Two Distinct Types of Ionocyte, and Probably
      Augments Ammonia Excretion in One of Them, in the Gills of the Climbing Perch
      Exposed to Seawater.
AB  - The freshwater climbing perch, Anabas testudineus, is an euryhaline teleost and
      an obligate air-breather with the ability to actively excrete ammonia. Members of
      the Na+/H+ exchanger (NHE) family help maintain intracellular pH homeostasis and
      ionic balance through the electroneutral exchange of Na+ and H+. This study aimed
      to obtain, from the gills of A. testudineus, the full cDNA coding sequence of
      nhe3, and to determine the effects of exposure to seawater or 100 mmol l-1 of
      NH4Cl in fresh water on its mRNA and protein expression levels. Efforts were also
      made to elucidate the type of ionocyte that Nhe3 was associated with in the
      branchial epithelium of A. testudineus. The transcript level and protein
      abundance of nhe3/Nhe3 were very low in the gills of freshwater A. testudineus,
      but they increased significantly in the gills of fish acclimated to seawater. In
      the gills of fish exposed to seawater, Nhe3 was expressed in two distinct types
      of seawater-inducible Na+/K+-ATPase (Nka)-immunoreactive ionocytes. In Nkaalpha1b
      immunoreactive ionocytes, Nhe3 had an apical localization. As these ionocytes
      also expressed apical Rhcg1 and basolateral Rhcg2, which are known to transport
      ammonia, they probably participated in proton-facilitated ammonia excretion in A.
      testudineus during seawater acclimation. In Nkaalpha1c-immunoreactive ionocytes,
      Nhe3 was atypically expressed in the basolateral membrane, and its physiological
      function is uncertain. For A. testudineus exposed to NH4Cl in fresh water, the
      transcript and protein expression levels of nhe3/Nhe3 remained low. In
      conclusion, the branchial Nhe3 of A. testudineus plays a greater physiological
      role in passive ammonia transport and acid-base balance during seawater
      acclimation than in active ammonia excretion during environmental ammonia
      exposure.

PMID- 29209225
TI  - CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in
      Models of Diastolic Dysfunction-A Cardiovascular Therapeutic: An Efficacy and
      Safety Study in the Rat.
AB  - The nitroxyl (HNO) prodrug, CXL-1020, induces vasorelaxation and improves cardiac
      function in canine models and patients with systolic heart failure (HF). HNO's
      unique mechanism of action may be applicable to a broader subset of cardiac
      patients. This study investigated the load-independent safety and efficacy of CXL
      1020 in two rodent (rat) models of diastolic heart failure and explored potential
      drug interactions with common HF background therapies. In vivo left-ventricular
      hemodynamics/pressure-volume relationships assessed before/during a 30 min IV
      infusion of CXL-1020 demonstrated acute load-independent positive inotropic,
      lusitropic, and vasodilatory effects in normal rats. In rats with only diastolic
      dysfunction due to bilateral renal wrapping (RW) or pronounced diastolic and mild
      systolic dysfunction due to 4 weeks of chronic isoproterenol exposure (ISO), CXL
      1020 attenuated the elevated LV filling pressures, improved the end diastolic
      pressure volume relationship, and accelerated relaxation. CXL-1020 facilitated
      Ca2+ re-uptake and enhanced myocyte relaxation in isolated cardiomyocytes from
      ISO rats. Compared to milrinone, CXL-1020 more effectively improved Ca2+ reuptake
      in ISO rats without concomitant chronotropy, and did not enhance Ca2+ entry via L
      type Ca2+ channels nor increase myocardial arrhythmias/ectopic activity. Acute
      therapy with CXL-1020 improved ventricular relaxation and Ca2+ cycling, in the
      setting of chronic induced diastolic dysfunction. CXL-1020's lusitropic effects
      were greater than those seen with the cAMP-dependent agent milrinone, and unlike
      milrinone it did not produce chronotropy or increased ectopy. HNO is a promising
      new potential therapy for both systolic and diastolic heart failure.

PMID- 29209226
TI  - Uncertainty Quantification Reveals the Importance of Data Variability and
      Experimental Design Considerations for in Silico Proarrhythmia Risk Assessment.
AB  - The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a global initiative
      intended to improve drug proarrhythmia risk assessment using a new paradigm of
      mechanistic assays. Under the CiPA paradigm, the relative risk of drug-induced
      Torsade de Pointes (TdP) is assessed using an in silico model of the human
      ventricular action potential (AP) that integrates in vitro pharmacology data from
      multiple ion channels. Thus, modeling predictions of cardiac risk liability will
      depend critically on the variability in pharmacology data, and uncertainty
      quantification (UQ) must comprise an essential component of the in silico assay.
      This study explores UQ methods that may be incorporated into the CiPA framework.
      Recently, we proposed a promising in silico TdP risk metric (qNet), which is
      derived from AP simulations and allows separation of a set of CiPA training
      compounds into Low, Intermediate, and High TdP risk categories. The purpose of
      this study was to use UQ to evaluate the robustness of TdP risk separation by
      qNet. Uncertainty in the model parameters used to describe drug binding and ionic
      current block was estimated using the non-parametric bootstrap method and a
      Bayesian inference approach. Uncertainty was then propagated through AP
      simulations to quantify uncertainty in qNet for each drug. UQ revealed lower
      uncertainty and more accurate TdP risk stratification by qNet when simulations
      were run at concentrations below 5* the maximum therapeutic exposure (Cmax).
      However, when drug effects were extrapolated above 10* Cmax, UQ showed that qNet
      could no longer clearly separate drugs by TdP risk. This was because for most of
      the pharmacology data, the amount of current block measured was <60%, preventing
      reliable estimation of IC50-values. The results of this study demonstrate that
      the accuracy of TdP risk prediction depends both on the intrinsic variability in
      ion channel pharmacology data as well as on experimental design considerations
      that preclude an accurate determination of drug IC50-values in vitro. Thus, we
      demonstrate that UQ provides valuable information about in silico modeling
      predictions that can inform future proarrhythmic risk evaluation of drugs under
      the CiPA paradigm.

PMID- 29209227
TI  - The Role of Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) in Dental Epithelium during
      Enamel Formation in Mice.
AB  - Na+:K+:2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled
      Cl- transporters. We investigated whether enamel-producing mouse ameloblasts
      express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental
      epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel
      epithelium and in the papillary layer but not the ameloblast layer. In incisors
      of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the
      mineral density of the enamel was reduced by 10% compared to wild-type controls.
      Protein levels of gap junction protein connexin 43, Na+-dependent bicarbonate
      cotransporter e1 (NBCe1), and the Cl--dependent bicarbonate exchangers SLC26A3
      and SLC26A6 were upregulated in Nkcc1-null enamel organs while the level of
      NCKX4/SLC24A4, the major K+, Na+ dependent Ca2+ transporter in maturation
      ameloblasts, was slightly downregulated. Whole-cell voltage clamp studies on rat
      ameloblast-like HAT-7 cells indicated that bumetanide increased ion-channel
      activity conducting outward currents. Bumetanide also reduced cell volume of HAT
      7 cells. We concluded that non-ameloblast dental epithelium expresses NKCC1 to
      regulate cell volume in enamel organ and provide ameloblasts with Na+, K+ and Cl-
      ions required for the transport of mineral- and bicarbonate-ions into enamel.
      Absence of functional Nkcc1 likely is compensated by other types of ion channels
      and ion transporters. The increased amount of Cx43 in enamel organ cells in Nkcc1
      null mice suggests that these cells display a higher number of gap junctions to
      increase intercellular communication.

PMID- 29209228
TI  - Commentary: Neutral Commentary on Frontiers Article "Cobalt Chloride Upregulates
      Impaired HIF-1alpha Expression to Restore Sevoflurane Post-conditioning-Dependent
      Myocardial Protection in Diabetic Rats".

PMID- 29209229
TI  - Proposal of a Global Training Load Measure Predicting Match Performance in an
      Elite Team Sport.
AB  - Aim: The use of external and internal load is an important aspect of monitoring
      systems in team sport. The aim of this study was to validate a novel measure of
      training load by quantifying the training-performance relationship of elite
      Australian footballers. Methods: The primary training measure of each of 36
      players was weekly load derived from a weighted combination of Global Positioning
      System (GPS) data and perceived wellness over a 24-week season. Smoothed loads
      representing an exponentially weighted rolling average were derived with decay
      time constants of 1.5, 2, 3, and 4 weeks. Differential loads representing rate of
      change in load were generated in similar fashion. Other derived measures of
      training included monotony, strain and acute:chronic ratio. Performance was a
      proprietary score derived from match performance indicators. Effects of a 1 SD
      within-player change below and above the mean of each training measure were
      quantified with a quadratic mixed model for each position (defenders, forwards,
      midfielders, and rucks). Effects were interpreted using standardization and
      magnitude-based inferences. Results: Performance was generally highest near the
      mean or ~1 SD below the mean of each training measure, and 1 SD increases in the
      following measures produced small impairments: weekly load (defenders, forwards,
      and midfielders); 1.5-week smoothed load (midfielders); 4-week differential load
      (defenders, forwards, and midfielders); and acute:chronic ratio (defenders and
      forwards). Effects of other measures in other positions were either trivial or
      unclear. Conclusion: The innovative combination of load was sensitive to
      performance in this elite Australian football cohort. Periods of high acute load
      and sustained increases in load impaired match performance. Positional
      differences should be taken into account for individual training prescription.

PMID- 29209230
TI  - Balanced Noise-Evoked Excitation and Inhibition in Awake Mice CA3.
AB  - The hippocampus is known as a neuronal structure involved in learning, memory and
      spatial navigation using multi-sensory cues. However, the basic features of its
      response to acoustic stimuli without any behavioral tasks (conditioning) remains
      poorly studied. Here, we investigated the CA3 response to auditory stimuli using
      in vivo loose-patch recordings in awake and anesthetized C57 mice. Different
      acoustic stimuli in addition to broadband noise such as click, FM sound and pure
      tone were applied to test the response of CA3 in awake animals. It was found that
      the wakefulness of the animal is important for the recorded neurons to respond.
      The CA3 neurons showed a stronger response to broadband noise rather than the
      other type of stimuli which suggested that auditory information arrived at CA3
      via broadband pathways. Finally, we investigated the excitatory and inhibitory
      inputs to CA3 neurons by using in vivo whole-cell voltage-clamp techniques with
      the membrane potential holding at -70 and 0 mV, respectively. In awake animals,
      the excitatory and inhibitory inputs CA3 neurons receive induced by noise are
      balanced by showing stable intervals and proportional changes of their latencies
      and peak amplitudes as a function of the stimulation intensities.

PMID- 29209231
TI  - Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3.
AB  - Odontogenesis results from the continuous and reciprocal interaction between
      cells of the oral epithelium and cranial neural crest-derived mesenchyme. The
      canonical Wnt signaling pathway plays a fundamental role in mediating these
      interactions from the earliest stages of tooth development. Here we analyze by in
      situ hybridization the expression patterns of the extracellular Wnt antagonist
      Frzb/Sfrp3. Although Frzb is expressed in dental mesenchymal cells from the
      earliest stages of odontogenesis, its expression is absent from a tiny population
      of mesenchymal cells immediately adjacent to the invaginating dental epithelium.
      Cell proliferation studies using BrdU showed that the Frzb expressing and Frzb
      non-expressing cell populations display different proliferative behavior during
      the initial stages of odontogenesis. DiI-mediated cell-fate tracing studies
      demonstrated that the Frzb expressing cells contribute to the formation of the
      dental follicle, the future periodontium. In contrast, the Frzb non-expressing
      cells give rise to the dental pulp. The present results indicate that Frzb is
      discriminating the presumptive periodontal territory from the rest of the dental
      mesenchyme from the very beginning of odontogenesis, where it might act as a
      barrier for the diffusion of Wnt molecules, thus regulating the activation of Wnt
      dependent transcription within dental tissues.

PMID- 29209232
TI  - The Clinicopathological and Prognostic Implications of FoxP3+ Regulatory T Cells
      in Patients with Colorectal Cancer: A Meta-Analysis.
AB  - Background and Objective: Forkhead box P3 (FoxP3) is known as the specific marker
      for regulatory T lymphocytes (Tregs), which are responsible for self-tolerance
      and disturb the antitumor immunity. However, the prognostic implication of tumor
      infiltrating FoxP3+ Tregs in patients with colorectal cancer (CRC) still remains
      controversial. The aim of this present study was to investigate the prognostic
      role of FoxP3+ Tregs in CRC through meta-analysis. Methods: PubMed, Embase and
      Web of Science were searched for relevant articles up to December 12, 2016.
      Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to
      explore the prognostic value of FoxP3+ Tregs in CRC. Odds ratio (OR) was
      calculated to investigate the correlation between FoxP3+ Tregs and pathological
      parameters. Results: A total of 18 studies comprising 3,627 patients with CRC
      were enrolled in our meta-analysis. The combined HR for FoxP3+ Tregs on cancer
      specific survival was 0.70 (95% CI = 0.62-0.80, P < 0.001). High FoxP3+ Tregs
      level was also associated with favorable prognosis on overall survival (HR =
      0.76, 95% CI = 0.58-1.01, P = 0.058), with P-value very close to the statistical
      threshold. Yet, there was no correlation between FoxP3+ Tregs infiltration and
      disease-free survival (HR = 0.83, 95% CI = 0.63-1.09, P = 0.182). Moreover,
      FoxP3+ Tregs infiltration was significantly correlated with pT stage (OR = 0.50,
      95% CI = 0.39-0.65, P < 0.001), tumor grade (OR = 0.77, 95% CI = 0.61-0.98, P =
      0.032), lymphatic invasion (OR = 0.25, 95% CI = 0.07-0.89, P = 0.033) and
      vascular invasion (OR = 0.67, 95% CI = 0.52-0.86, P = 0.001). Conclusion: The
      present meta-analysis suggests that high FoxP3+ Tregs infiltration is inclined to
      indicate favorable prognosis and is associated with the pathogenesis of CRC.
      Immunotherapy targeting Tregs in patients with CRC should be further
      investigated.

PMID- 29209233
TI  - Chemosensory Gene Families in Ectropis grisescens and Candidates for Detection of
      Type-II Sex Pheromones.
AB  - Tea grey geometrid (Ectropis grisescens), a devastating chewing pest in tea
      plantations throughout China, produces Type-II pheromone components. Little is
      known about the genes encoding proteins involved in the perception of Type-II sex
      pheromone components. To investigate the olfaction genes involved in E.
      grisescens sex pheromones and plant volatiles perception, we sequenced female and
      male antennae transcriptomes of E. grisescens. After assembly and annotation, we
      identified 153 candidate chemoreception genes in E. grisescens, including 40
      odorant-binding proteins (OBPs), 30 chemosensory proteins (CSPs), 59 odorant
      receptors (ORs), and 24 ionotropic receptors (IRs). The results of phylogenetic,
      qPCR, and mRNA abundance analyses suggested that three candidate pheromone
      binding proteins (EgriOBP2, 3, and 25), two candidate general odorant-binding
      proteins (EgriOBP1 and 29), six pheromone receptors (EgriOR24, 25, 28, 31, 37,
      and 44), and EgriCSP8 may be involved in the detection of Type-II sex pheromone
      components. Functional investigation by heterologous expression in Xenopus
      oocytes revealed that EgriOR31 was robustly tuned to the E. grisescens sex
      pheromone component (Z,Z,Z)-3,6,9-octadecatriene and weakly to the other sex
      pheromone component (Z,Z)-3,9-6,7-epoxyoctadecadiene. Our results represent a
      systematic functional analysis of the molecular mechanism of olfaction perception
      in E. grisescens with an emphasis on gene encoding proteins involved in
      perception of Type-II sex pheromones, and provide information that will be
      relevant to other Lepidoptera species.

PMID- 29209234
TI  - Altered Brain Functional Connectivity in Betel Quid-Dependent Chewers.
AB  - Background: Betel quid (BQ) is a common psychoactive substance worldwide with
      particularly high usage in many Asian countries. This study aimed to explore the
      effect of BQ use on functional connectivity by comparing global functional brain
      networks and their subset between BQ chewers and healthy controls (HCs). Methods:
      Resting-state functional magnetic resonance imaging (fMRI) was obtained from 24
      betel quid-dependent (BQD) male chewers and 27 healthy male individuals on a 3.0T
      scanner. We used independent component analysis (ICA) to determine components
      that represent the brain's functional networks and their spatial aspects of
      functional connectivity. Two sample t-tests were used to identify the functional
      connectivity differences in each network between these two groups. Results:
      Seventeen networks were identified by ICA. Nine of them showed connectivity
      differences between BQD and HCs (two sample t-tests, p < 0.001 uncorrected). We
      found increased functional connectivity in the orbitofrontal, bilateral
      frontoparietal, frontotemporal, occipital/parietal, frontotemporal/cerebellum,
      and temporal/limbic networks, and decreased connectivity in the parietal and
      medial frontal/anterior cingulate networks in the BQD compared to the HCs. The
      betel quid dependence scale scores were positively related to the increased
      functional connectivity in the orbitofrontal (r = 0.39, p = 0.03) while
      negatively related to the decreased functional connectivity in medial
      frontal/anterior cingulate networks (r = -0.35, p = 0.02). Discussion: Our
      findings provide further evidence that BQ chewing may lead to brain functional
      connectivity changes, which may play a key role in the psychological and
      physiological effects of BQ.

PMID- 29209235
TI  - The "Endless Trip" among the NPS Users: Psychopathology and Psychopharmacology in
      the Hallucinogen-Persisting Perception Disorder. A Systematic Review.
AB  - Hallucinogen-persisting perception disorder (HPPD) is a syndrome characterized by
      prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen
      effects. HPPD was associated with a broader range of LSD (lysergic acid
      diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (MDMA),
      psilocybin, mescaline, and psychostimulants. The recent emergence of novel
      psychoactive substances (NPS) posed a critical concern regarding the new onset of
      psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly
      comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes,
      flashes of colors/lights, motion-perception deficits, afterimages, micropsia,
      more acute awareness of floaters, etc.), even though depressive symptoms and
      thought disorders may be comorbidly present. Although HPPD was first described in
      1954, it was just established as a fully syndrome in 2000, with the revised
      fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      IV-TR). HPPD neural substrates, risk factors, and aetiopathogenesys still largely
      remain unknown and under investigation, and many questions about its
      pharmacological targets remain unanswered too. A critical mini review on
      psychopathological bases, etiological hypothesis, and psychopharmacological
      approaches toward HPPD, including the association with some novel substances, are
      provided here, by means of a literature search on PubMed/Medline, Google Scholar,
      and Scopus databases without time restrictions, by using a specific set of
      keywords. Pharmacological and clinical issues are considered, and practical
      psychopharmacological recommendations and clinical guidelines are suggested.

PMID- 29209236
TI  - Implementation Intention for Initiating Intuitive Eating and Active Embodiment in
      Obese Patients Using a Smartphone Application.
AB  - This article describes a study protocol, which aims to explore and describe the
      feasibility of a mobile-phone application for initiating intuitive eating and
      intuitive exercising in patients who are following an ambulatory treatment for
      obesity. Intuitive eating refers to one's ability to make food choices based on
      one's awareness of his/her body's response. Intuitive exercising encourages
      people in finding enjoyable ways of being physically active. These two components
      will be trained using an implementation intention procedure, that is, behavioral
      plans that aim at creating a strong link between a specified situation and a
      response. We aim to recruit up to 80 overweight and obese patients over a period
      of 2 years. The smartphone application will be assessed on the basis of (i) data
      obtained through a 4-week use period, (ii) self-report measures taken before and
      after the use of the mobile application, and (iii) feedbacks from participants
      after the use of the mobile application. This pilot study will allow us to better
      understand the applicability of the use of mobile application within ambulatory
      treatment settings, and to adapt the design of the app necessary for building
      cross-sectional studies investigating its efficacy.

PMID- 29209237
TI  - Decreased Left Putamen and Thalamus Volume Correlates with Delusions in First
      Episode Schizophrenia Patients.
AB  - Background: Delusional thinking is one of the hallmark symptoms of schizophrenia.
      However, the underlying neural substrate for delusions in schizophrenia remains
      unknown. In an attempt to further our understanding of the neural basis of
      delusions, we explored gray matter deficits and their clinical associations in
      first-episode schizophrenia patients with and without delusions. Methods: Twenty
      four first-episode schizophrenia patients with delusions and 18 without delusions
      as well as 26 healthy controls (HC) underwent clinical assessment and whole-brain
      structural imaging which were acquired a 3.0 T scanner. Voxel-based morphometry
      was used to explore inter-group differences in gray matter volume using analysis
      of covariance, and Spearman correlation coefficients (rho) between the Scale for
      the Assessment of Positive Symptoms (SAPS)-delusion scores and mean regional
      brain volumes was obtained. Results: Patients with delusions showed decreased
      brain gray matter volumes in the left putamen, thalamus, and caudate regions
      compared with HC. Patients with delusions also showed decreased regional volume
      in the left putamen and thalamus compared with patients without delusions. SAPS
      delusion scores were negatively correlated with the gray matter volumes of the
      left putamen and thalamus. Discussion: Left putamen and thalamus volume loss may
      be biological correlates of delusions in schizophrenia.

PMID- 29209238
TI  - Disrupted Control-Related Functional Brain Networks in Drug-Naive Children with
      Attention-Deficit/Hyperactivity Disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental
      disease featuring executive control deficits as a prominent neuropsychological
      trait. Executive functions are implicated in multiple sub-networks of the brain;
      however, few studies examine these sub-networks as a whole in ADHD. By combining
      resting-state functional MRI and graph-based approaches, we systematically
      investigated functional connectivity patterns among four control-related
      networks, including the frontoparietal network (FPN), cingulo-opercular network,
      cerebellar network, and default mode network (DMN), in 46 drug-naive children
      with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy
      controls (HCs). Compared to the HCs, the ADHD children showed significantly
      decreased functional connectivity that primarily involved the DMN and FPN regions
      and cross-network long-range connections. Further graph-based network analysis
      revealed that the ADHD children had fewer connections, lower network efficiency,
      and more functional modules compared with the HCs. The ADHD-related alterations
      in functional connectivity but not topological organization were correlated with
      clinical symptoms of the ADHD children and differentiated the patients from the
      HCs with a good performance. Taken together, our findings suggest a less
      integrated functional brain network in children with ADHD due to selective
      disruption of key long-range connections, with important implications for
      understanding the neural substrates of ADHD, particularly executive dysfunction.

PMID- 29209240
TI  - Different Bilingual Experiences Might Modulate Executive Tasks Advantages:
      Comparative Analysis between Monolinguals, Translators, and Interpreters.
AB  - Many studies have shown that being bilingual presents an advantage in executive
      control. However, it appears that knowing two (or more) languages is not enough
      to improve executive control. According to the adaptive control hypothesis (Green
      and Abutalebi, 2013), the interactional context in which bilinguals behave is a
      key factor that modulates cognitive advantage in executive control. Translation
      and simultaneous interpretation are performed in a dual-language context:
      professional bi- and multilinguals use two or more languages within the same
      context (at work). Simultaneous interpretation differs from translation though,
      because of its higher level of time pressure, which increases the cognitive
      demands on executive control. The main objective of the present study is to
      investigate the relationship between simultaneous interpretation and some aspects
      of executive control. To this end, we compare the performance of three groups (60
      interpreters, 60 translators, and 60 monolinguals) in five computerized tasks
      designed to assess different executive processes as well as the speed of
      information processing. The results show that the interpreters perform better
      than the monolinguals in all tasks and better than the translators in all tasks
      except for the one designed to assess flexibility. The results also show that the
      age variable does not have the same effect on performance in tasks designed to
      assess updating, flexibility, and resistance of proactive inhibition in
      bilinguals (both interpreters and translators), or in tasks designed to assess
      the speed of information processing and inhibition of a prepotent response in
      interpreters only. In addition to the advantage that being bilingual presents in
      some aspects of executive control, the results suggest that interpreters have an
      additional advantage that may be explained by the characteristics of their work
      activity (especially heavy time pressure) and by how much experience they have in
      this activity (in terms of magnitude of the bilingual management demands and
      amount of experience in managing the cognitive demands of simultaneous
      interpretation).

PMID- 29209239
TI  - Genetic Biomarkers on Age-Related Cognitive Decline.
AB  - With ever-increasing elder populations, age-related cognitive decline, which is
      characterized as a gradual decline in cognitive capacity in the aging process,
      has turned out to be a mammoth public health concern. Since genetic information
      has become increasingly important to explore the biological mechanisms of
      cognitive decline, the search for genetic biomarkers of cognitive aging has
      received much attention. There is growing evidence that single-nucleotide
      polymorphisms (SNPs) within the ADAMTS9, BDNF, CASS4, COMT, CR1, DNMT3A, DTNBP1,
      REST, SRR, TOMM40, circadian clock, and Alzheimer's diseases-associated genes may
      contribute to susceptibility to cognitive aging. In this review, we first
      illustrated evidence of the genetic contribution to disease susceptibility to age
      related cognitive decline in recent studies ranging from approaches of candidate
      genes to genome-wide association studies. We then surveyed a variety of
      association studies regarding age-related cognitive decline with consideration of
      gene-gene and gene-environment interactions. Finally, we highlighted their
      limitations and future directions. In light of advances in precision medicine and
      multi-omics technologies, future research in genomic medicine promises to lead to
      innovative ideas that are relevant to disease prevention and novel drugs for
      cognitive aging.

PMID- 29209241
TI  - Sentence-Level Effects of Literary Genre: Behavioral and Electrophysiological
      Evidence.
AB  - The current study used event-related brain potentials (ERPs) and behavioral
      measures to examine effects of genre awareness on sentence processing and
      evaluation. We hypothesized that genre awareness modulates effects of genre
      typical manipulations. We manipulated instructions between participants, either
      specifying a genre (poetry) or not (neutral). Sentences contained genre-typical
      variations of semantic congruency (congruent/incongruent) and morpho-phonological
      features (archaic/contemporary inflections). Offline ratings of meaningfulness (n
      = 64/group) showed higher average ratings for semantically incongruent sentences
      in the poetry vs. neutral condition. ERPs during sentence reading (n = 24/group;
      RSVP presentation at a fixed per-constituent rate; probe task) showed a left
      lateralized N400-like effect for contemporary vs. archaic inflections. Semantic
      congruency elicited a bilateral posterior N400 effect for incongruent vs.
      congruent continuations followed by a centro-parietal positivity (P600). While
      N400 amplitudes were insensitive to the genre, the latency of the P600 was
      delayed by the poetry instruction. From these results, we conclude that during
      real-time sentence comprehension, readers are sensitive to subtle morphological
      manipulations and the implicit prosodic differences that accompany them. By
      contrast, genre awareness affects later stages of comprehension.

PMID- 29209242
TI  - Patterns of Eye Movements When Observers Judge Female Facial Attractiveness.
AB  - The purpose of the present study is to explore the fixed model for the explicit
      judgments of attractiveness and infer which features are important to judge the
      facial attractiveness. Behavioral studies on the perceptual cues for female
      facial attractiveness implied three potentially important features: averageness,
      symmetry, and sexual dimorphy. However, these studies did not explained which
      regions of facial images influence the judgments of attractiveness. Therefore,
      the present research recorded the eye movements of 24 male participants and 19
      female participants as they rated a series of 30 photographs of female facial
      attractiveness. Results demonstrated the following: (1) Fixation is longer and
      more frequent on the noses of female faces than on their eyes and mouths (no
      difference exists between the eyes and the mouth); (2) The average pupil diameter
      at the nose region is bigger than that at the eyes and mouth (no difference
      exists between the eyes and the mouth); (3) the number of fixations of male
      participants was significantly more than female participants. (4) Observers first
      fixate on the eyes and mouth (no difference exists between the eyes and the
      mouth) before fixating on the nose area. In general, participants attend
      predominantly to the nose to form attractiveness judgments. The results of this
      study add a new dimension to the existing literature on judgment of facial
      attractiveness. The major contribution of the present study is the finding that
      the area of the nose is vital in the judgment of facial attractiveness. This
      finding establish a contribution of partial processing on female facial
      attractiveness judgments during eye-tracking.

PMID- 29209243
TI  - Love Influences Reproductive Success in Humans.
AB  - As love seems to be universal, researchers have attempted to find its biological
      basis. However, no studies till date have shown its direct association with
      reproductive success, which is broadly known to be a good measure of fitness.
      Here, we show links between love, as defined by the Sternberg Triangular Theory
      of Love, and reproductive success among the Hadza-traditional hunter-gatherer
      population. We found that commitment and reproductive success were positively and
      consistently related in both sexes, with number of children showing negative and
      positive associations with intimacy and passion, respectively, only among women.
      Our study may shed new light on the meaning of love in humans' evolutionary past,
      especially in traditional hunter-gatherer societies in which individuals, not
      their parents, were responsible for partner choice. We suggest that passion and
      commitment may be the key factors that increase fitness, and therefore, that
      selection promoted love in human evolution. However, further studies in this area
      are recommended.

PMID- 29209244
TI  - Processing of a Subliminal Rebus during Sleep: Idiosyncratic Primary versus
      Secondary Process Associations upon Awakening from REM- versus Non-REM-Sleep.
AB  - Primary and secondary processes are the foundational axes of the Freudian mental
      apparatus: one horizontally as a tendency to associate, the primary process, and
      one vertically as the ability for perspective taking, the secondary process.
      Primary process mentation is not only supposed to be dominant in the unconscious
      but also, for example, in dreams. The present study tests the hypothesis that the
      mental activity during REM-sleep has more characteristics of the primary process,
      while during non-REM-sleep more secondary process operations take place. Because
      the solving of a rebus requires the ability to non-contexually condensate the
      literal reading of single stimuli into a new one, rebus solving is a primary
      process operation by excellence. In a replication of the dream-rebus study of
      Shevrin and Fisher (1967), a rebus, which consisted of an image of a comb
      (German: "Kamm") and an image of a raft (German: "Flobeta"), resulting in the
      German rebus word "kampflos" (Engl.: without a struggle), was flashed
      subliminally (at 1 ms) to 20 participants before going to sleep. Upon consecutive
      awakenings participants were asked for a dream report, free associations and an
      image description. Based on objective association norms, there were significantly
      more conceptual associations referring to Kamm and Flobeta indexing secondary
      process mentation when subjects were awakened from non-REM sleep as compared to
      REM-awakenings. There were not significantly more rebus associations referring to
      kampflos indexing primary process mentation when awakened from REM-sleep as
      compared to non-REM awakenings. However, when the associations were scored on the
      basis of each subject's individual norms, there was a rebus effect with more
      idiosyncratic rebus associations in awakenings after REM than after non-REM
      sleep. Our results support the general idea that REM-sleep is characterized by
      primary process thinking, while non-REM-sleep mentation follows the rules of the
      secondary process.

PMID- 29209246
TI  - Cultural Value Orientations and Alcohol Consumption in 74 Countries: A Societal
      Level Analysis.
AB  - A significant proportion of all deaths globally can be attributed to alcohol
      consumption. Although a range of correlates of alcohol consumption have already
      been identified at the individual level, less is understood about correlates at
      the macro level, such as cultural values. As a development in this understanding
      may prove useful for global health organizations aiming to tackle the problems
      associated with excessive drinking, our aim was to investigate the association
      between encultured alcohol consumption and Cultural Value Orientations. We
      obtained data describing average alcohol consumption and Cultural Value
      Orientations, for 74 countries, from an online data repository. To assess whether
      Cultural Value Orientations are associated with alcohol consumption we calculated
      partial correlations and performed a ridge regression analysis. Our analyses
      revealed that Cultural Value Orientations were significantly associated with
      alcohol consumption, even after controlling for average income and education
      level. A profile emerged in which values of autonomy and harmony were shown to be
      positively associated with alcohol consumption, and hierarchy and embeddedness
      negatively associated with alcohol consumption. The effect was modified by
      gender. Changes in cultural Harmony, Mastery, Autonomy and Egalitarianism were
      associated with increases in alcohol consumption in males, but not females, while
      changes in cultural Embeddedness and Hierarchy were associated with decreases in
      consumption in females, but no change in males. Finally, we demonstrate that
      latitude, and by extension its covariates such as climatic demands, partially
      accounted for the effect of harmony and affective autonomy on alcohol
      consumption. This research highlights that cultural values, and their interaction
      with gender, should be an important consideration for international public health
      organizations aiming to tackle the problems associated with alcohol consumption,
      but that future research is required to fully understand the link between
      cultural values and alcohol.

PMID- 29209245
TI  - Identification and Description of Novel Mood Profile Clusters.
AB  - Mood profiling has been a popular assessment strategy since the 1970s, although
      little evidence exists of distinct mood profiles beyond the realm of sport and
      exercise. In the present study, we investigated clusters of mood profiles derived
      from the six subscales of the Brunel Mood Scale using the In The Mood website.
      Mood responses in three samples (n = 2,364, n = 2,303, n = 1,865) were analyzed
      using agglomerative, hierarchical cluster analysis, which distinguished six
      distinct and theoretically meaningful profiles. K-means clustering further
      refined the final parameter solution. Mood profiles identified were termed the
      iceberg, inverse iceberg, inverse Everest, shark fin, surface, and submerged
      profiles. Simultaneous multiple discriminant function analysis showed that
      cluster membership was correctly classified with a high degree of accuracy. Chi
      squared tests indicated that the six mood profiles were unequally distributed
      according to the gender, age, and education of participants. Future research
      should investigate the antecedents, correlates and consequences of these six mood
      profile clusters.

PMID- 29209247
TI  - Translation, Adaptation, and Validation of the Brazilian Version of the Dickman
      Impulsivity Inventory (Br-DII).
AB  - Impulsivity has mainly been described as a negative or dysfunctional
      characteristic associated with several disorders. However, impulsivity is not
      only related to dysfunctional outcomes and may explain individual differences in
      optimal human functioning as well. The Dickman Impulsivity Inventory (DII) is a
      self-report instrument measuring both the dysfunctional and the functional
      aspects of impulsivity. In this study, we performed the translation and cultural
      adaptation of the DII to the Brazilian context and analyzed its psychometric
      properties. Translation and cultural adaptation followed a rigorous process,
      which relied on an expert panel in the cross-cultural adaptation of psychological
      instruments. Data from 405 undergraduate students were obtained for the Brazilian
      version of the DII (Br-DII). The 23 items of the Br-DII was considered unsuitable
      according to model fit indices of the Confirmatory Factor Analysis (both for
      Oblique and Orthogonal models). Exploratory Factor Analysis showed an 18 items
      version of the Br-DII to be suitable (CFI = 0.92; TLI = 0.90, and RMSEA = 0.057).
      The DII's 18 items version also showed adequate Cronbach's alpha, intraclass
      correlation coefficient, and convergent and discriminant validity with the BIS
      11. Therefore, the Br-DII demonstrated reliability and validity in the
      measurement of functional and dysfunctional impulsivity.

PMID- 29209248
TI  - Hardcore Heritage: Imagination for Preservation.

PMID- 29209249
TI  - Educational and Cognitive Predictors of Pro- and Antisaccadic Performance.
AB  - Voluntary gaze control allows people to direct their attention toward selected
      targets while avoiding distractors. Failure in this ability could be related to
      dysfunctions in the neural circuits underlying executive functions.
      Interestingly, recent evidence suggests that factors such as years of schooling
      and literacy may positively influence goal-directed behavior and inhibitory
      control. However, we do not yet know whether these factors also have a
      significant impact on the inhibitory control of oculomotor responses. Using pro-
      and antisaccadic tasks to assess the behavioral responses of healthy adults, we
      tested the contribution of years of schooling and reading proficiency to their
      oculomotor control, while simultaneously analyzing the effects of other
      individual characteristics related to demographic, cognitive and motor profiles.
      This approach allowed us to test the hypothesis that schooling factors are
      closely related to oculomotor performance. Indeed, a regression analysis revealed
      important contributions of reading speed and intellectual functioning to the
      choices on both pro- and antisaccadic tasks, while years of schooling, age and
      block sequence emerged as important predictors of the kinematic properties of eye
      movements on antisaccadic tasks. Thus, our findings show that years of schooling
      and reading speed had a strong predictive influence on the oculomotor measures,
      although age and order of presentation also influenced saccadic performance, as
      previously reported. Unexpectedly, we found that an indirect measure of
      intellectual ability also proved to be a good predictor of the control of
      saccadic movements. The methods and findings of this study will be useful for
      identifying and breaking down the cognitive and educational components involved
      in assessing voluntary and automatic responses.

PMID- 29209250
TI  - Mental Simulation of Painful Situations Has an Impact on Posture and
      Psychophysiological Parameters.
AB  - Embodiment is made possible by the ability to imagine ourselves in a particular
      situation (mental simulation). Postural changes have been demonstrated in
      response to painful situations, but the effect of an implicit instruction has not
      been studied. The present study was designed to record differential responses
      according to whether or not subjects were instructed to imagine themselves in a
      painful or non-painful situation. Painful stimuli and instructions to mentally
      simulate the displayed situation were hypothesized to induce postural changes
      that could be demonstrated by changes in the center of pressure (COP) trajectory
      compared to viewing the same stimuli with no instructions. We hypothesized that
      mental simulation of a painful situation would induce embodiment of the emotional
      situation as reflected by posterior displacement of the COP and physiological
      responses as compared to passive observation of the same visual scene. Thirty-one
      subjects participated in this study while standing quietly on a posturographic
      platform with presentation of visual stimuli depicting scenes defining three
      experimental conditions (painful, non-painful and neutral situations) for 12 s.
      Physiological measurements [heart rate (HR) and electrodermal activity] and
      postural responses (COP displacements) were recorded in response to the stimuli
      with or without instructions to imagine themselves in the situation. Time-course
      analyses (1 s sliding window) were conducted for several postural parameters, HR
      and electrodermal response. An interaction effect (instruction * stimuli * time)
      demonstrated that mental simulation induced posterior displacement of the mean
      position of the COP at different times during presentation of visual stimuli (4
      s; 9-12 s). An effect of instruction was reported for HR (HR was higher in the
      mental simulation condition), while a stimulation effect was reported only for HR
      (lower for painful stimuli than for non-painful stimuli). The results of time
      course analyses demonstrated embodiment of painful situations by postural control
      modulations and physiological changes depending on whether or not the
      participants were instructed to imagine themselves in the situation.

PMID- 29209251
TI  - Social Cognition and Executive Functions As Key Factors for Effective Pedagogy in
      Higher Education.
AB  - Higher education (HE) faces the challenge of responding to an increasing
      diversity. In this context, more attention is being paid to teachers and teaching
      skills positively related to students learning. Beyond the knowledges identified
      as key components of an effective teacher, teachers also need to be capable of
      unraveling what their students think and believe, and how they accommodate the
      new information. More importantly, teachers need to be able to adapt their own
      teaching to their audience's needs. In learners, social cognition (SC) has been
      related to a better receptivity to the different teacher-student interactions.
      Since these interactions are bidirectional, SC could also help to explain
      teachers' receptiveness to the information available in feedback situations.
      However, little is known about how SC is related to teacher development, and
      therefore teaching effectiveness, in HE. In addition, executive functions (EFs),
      closely related to SC, could play a key role in the ability to self-regulate
      their own teaching to better answering their students emerging needs. Although
      there is wide evidence regarding the association of EFs to performance in high
      demanding settings, as far as we know, there are no studies exploring the
      relationship between teachers' EFs and teaching effectiveness in HE. Establishing
      a positive association between teaching effectiveness and these socio-cognitive
      functions could be a promising first step in designing professional development
      programs that promote HE academics' ability to understand and care about students
      thoughts and emotions, to eventually adapt their teaching to their students needs
      for a better learning.

PMID- 29209252
TI  - Role of a Semiotics-Based Curriculum in Empathy Enhancement: A Longitudinal Study
      in Three Dominican Medical Schools.
AB  - Background: Empathy in the context of patient care is defined as a predominantly
      cognitive attribute that involves an understanding of the patient's experiences,
      concerns, and perspectives, combined with a capacity to communicate this
      understanding and an intention to help. In medical education, it is recognized
      that empathy can be improved by interventional approaches. In this sense, a
      semiotic-based curriculum could be an important didactic tool for improving
      medical empathy. The main purpose of this study was to determine if in medical
      schools where a semiotic-based curriculum is offered, the empathetic orientation
      of medical students improves as a consequence of the acquisition and development
      of students' communication skills that are required in clinician-patient
      encounters. Design: This quasi-experimental study was conducted in three medical
      schools of the Dominican Republic that offer three different medical curricula:
      (i) a theoretical and practical semiotic-based curriculum; (ii) a theoretical
      semiotic-based curriculum; and (iii) a curriculum without semiotic courses. The
      Jefferson scale of empathy was administered in two different moments to students
      enrolled in pre-clinical cycles of those institutions. Data was subjected to
      comparative statistical analysis and logistic regression analysis. Results: The
      study included 165 students (55 male and 110 female). Comparison analysis showed
      statistically significant differences in the development of empathy among groups
      (p < 0.001). Logistic regression confirmed that gender, age, and a semiotic-based
      curriculum contributed toward the enhancement of empathy. Conclusion: These
      findings demonstrate the importance of medical semiotics as a didactic teaching
      method for improving beginners' empathetic orientation in patients' care.

PMID- 29209253
TI  - Improvement of Navigation and Representation in Virtual Reality after Prism
      Adaptation in Neglect Patients.
AB  - Prism adaptation (PA) is responsible for an expansion of sensori-motor after
      effects to cognitive domains for patients with spatial neglect. One important
      question is whether the cognitive after-effects induced by PA may also concern
      higher aspects of spatial cognition, such as navigation and topographic memory,
      which are critical in everyday life. The aim of this study was to assess whether
      multiple sessions of right PA can affect navigation and topographic memory. Seven
      right brain-damaged (RBD) patients with chronic neglect were included. We used a
      virtual supermarket named VAP-S which is an original paradigm, similar to the
      "shopping list test" during which patients had to purchase items from a list of
      eight products. Furthermore, in order to assess generalization of PA effects on
      constructing a spatial map from virtual information, each participant was then
      asked to draw the map of the virtual supermarket from memory. Regarding
      navigation performance, significant results were obtained: session duration
      reduction, fewer numbers of pauses and omissions, more items purchased on the
      left side and more items purchased over all. A long-lasting effect was noted, up
      to one month after PA. The representational task performance was also
      significantly increased for map drawing, with a reduction of the right shift of
      the symmetry axis of the map, more items drawn on the left side of maps and over
      all, and more items correctly located on the map. Some of these effects lasted
      for at least 7 days. These results suggest an expansion of PA benefit to a
      virtual environment. Crucially, the cognitive benefits induced by PA were noted
      for complex spatial cognition tasks required in everyday life such as navigation
      and topographic memory and this improvement was maintained for up to 1 month.

PMID- 29209254
TI  - Psychometric Properties of Multi-Dimensional Scale of Perceived Social Support in
      Chinese Parents of Children with Cerebral Palsy.
AB  - The Multi-dimensional Scale of Perceived Social Support (MSPSS) is one of the
      most extensively used instruments to assess social support. The purpose of this
      research was to test the reliability, factorial validity, concurrent validity and
      measurement invariance across gender groups of the MSPSS in Chinese parents of
      children with cerebral palsy. A total of 487 participants aged 21-55 years were
      recruited to complete the Chinese MSPSS and Parenting Stress Index-Short Form
      (PSI-SF). Composite reliability was calculated as the internal consistency of the
      Chinese MSPSS and a (multi-group) confirmatory factor analysis (CFA) was
      conducted to test the factorial validity and measurement invariance across
      gender. And Pearson correlations were calculated to test the relationships
      between MSPSS and PSI-SF. The Chinese MSPSS had satisfactory internal reliability
      with composite reliability values of more than 0.7. The CFA indicated that the
      original three-factor model was replicated in this specific population.
      Importantly, the results of the multi-group CFA demonstrated that configural,
      metric, and scalar invariance across gender groups was supported. In addition,
      all the three subscales of MSPSS were significant related with PSI-SF. These
      findings suggest that the Chinese MSPSS is a reliable and valid tool for
      assessing social support and can generally be utilized across sex in the parents
      of children with cerebral palsy.

PMID- 29209255
TI  - Potential for Assessing Dynamic Problem-Solving at the Beginning of Higher
      Education Studies.
AB  - There is a growing demand for assessment instruments which can be used in higher
      education, which cover a broader area of competencies than the traditional tests
      for disciplinary knowledge and domain-specific skills, and which measure
      students' most important general cognitive capabilities. Around the age of the
      transition from secondary to tertiary education, such assessments may serve
      several functions, including selecting the best-prepared candidates for certain
      fields of study. Dynamic problem-solving (DPS) is a good candidate for such a
      role, as tasks that assess it involve knowledge acquisition and knowledge
      utilization as well. The purpose of this study is to validate an online DPS test
      and to explore its potential for assessing students' DPS skills at the beginning
      of their higher education studies. Participants in the study were first-year
      students at a major Hungarian university (n = 1468). They took five tests that
      measured knowledge from their previous studies: Hungarian language and
      literature, mathematics, history, science and English as a Foreign Language
      (EFL). A further, sixth test based on the MicroDYN approach, assessed students'
      DPS skills. A brief questionnaire explored learning strategies and collected data
      on students' background. The testing took place at the beginning of the first
      semester in three 2-h sessions. Problem-solving showed relatively strong
      correlations with mathematics (r = 0.492) and science (r = 0.401), and moderate
      correlations with EFL (r = 0.227), history (r = 0.192), and Hungarian (r =
      0.125). Weak but still significant correlations were found with certain learning
      strategies, positive correlations with elaboration strategies, and a negative
      correlation with memorization strategies. Significant differences were observed
      between male and female students; men performed significantly better in DPS than
      women. Results indicated the dominant role of the first phase of solving dynamic
      problems, as knowledge acquisition correlated more strongly with any other
      variable than knowledge utilization.

PMID- 29209256
TI  - Low Mood Leads to Increased Empathic Distress at Seeing Others' Pain.
AB  - Previous studies have shown changes in empathy in patients with depression,
      including an elevated level of trait personal distress. This study examined if
      low mood causes changes in self-reported empathic distress when seeing others in
      pain. To test this, we conducted an initial (n = 26) and close replication study
      (n = 46) in which sad mood was induced in healthy participants (overall mean age
      M = 21, SD = 5, range = 18-41 years). Participants viewed and rated video stimuli
      inferring pain experienced by other people. Results showed that participants
      perceived the videos depicting others' pain (versus no-pain) to be more
      distressing under a sad mood compared to a neutral mood condition, implying that
      sadness enhances one's emotional reactivity toward others' distress. This
      supports previous depression literature suggesting an impaired emotional
      processing ability, and could contribute to some of the unhelpful behaviors seen
      in depression such as social withdrawal and avoidance.

PMID- 29209257
TI  - The Sound of Success: Investigating Cognitive and Behavioral Effects of
      Motivational Music in Sports.
AB  - Listening to music before, during, or after sports is a common phenomenon, yet
      its functions and effects on performance, cognition, and behavior remain to be
      investigated. In this study we present a novel approach to the role of music in
      sports and exercise that focuses on the notion of musical self-enhancement
      (Elvers, 2016). We derived the following hypotheses from this framework:
      listening to motivational music will (i) enhance self-evaluative cognition, (ii)
      improve performance in a ball game, and (iii) evoke greater risk-taking behavior.
      To evaluate the hypotheses, we conducted a between-groups experiment (N = 150)
      testing the effectiveness of both an experimenter playlist and a participant
      selected playlist in comparison to a no-music control condition. All participants
      performed a ball-throwing task developed by Decharms and Dave (1965), consisting
      of two parts: First, participants threw the ball from fixed distances into a
      funnel basket. During this task, performance was measured. In the second part,
      the participants themselves chose distances from the basket, which allowed their
      risk-taking behavior to be assessed. The results indicate that listening to
      motivational music led to greater risk taking but did not improve ball-throwing
      performance. This effect was more pronounced in male participants and among those
      who listened to their own playlists. Furthermore, self-selected music enhanced
      state self-esteem in participants who were performing well but not in those who
      were performing poorly. We also discuss further implications for the notion of
      musical self-enhancement.

PMID- 29209258
TI  - Syntactic and Story Structure Complexity in the Narratives of High- and Low
      Language Ability Children with Autism Spectrum Disorder.
AB  - Although language impairment is commonly associated with the autism spectrum
      disorder (ASD), the Diagnostic Statistical Manual no longer includes language
      impairment as a necessary component of an ASD diagnosis (American Psychiatric
      Association, 2013). However, children with ASD and no comorbid intellectual
      disability struggle with some aspects of language whose precise nature is still
      outstanding. Narratives have been extensively used as a tool to examine lexical
      and syntactic abilities, as well as pragmatic skills in children with ASD. This
      study contributes to this literature by investigating the narrative skills of 30
      Greek-speaking children with ASD and normal non-verbal IQ, 16 with language
      skills in the upper end of the normal range (ASD-HL), and 14 in the lower end of
      the normal range (ASD-LL). The control group consisted of 15 age-matched
      typically-developing (TD) children. Narrative performance was measured in terms
      of both microstructural and macrostructural properties. Microstructural
      properties included lexical and syntactic measures of complexity such as
      subordinate vs. coordinate clauses and types of subordinate clauses.
      Macrostructure was measured in terms of the diversity in the use of internal
      state terms (ISTs) and story structure complexity, i.e., children's ability to
      produce important units of information that involve the setting, characters,
      events, and outcomes of the story, as well as the characters' thoughts and
      feelings. The findings demonstrate that high language ability and syntactic
      complexity pattern together in ASD children's narrative performance and that
      language ability compensates for autistic children's pragmatic deficit associated
      with the production of Theory of Mind-related ISTs. Nevertheless, both groups of
      children with ASD (high and low language ability) scored lower than the TD
      controls in the production of Theory of Mind-unrelated ISTs, modifier clauses and
      story structure complexity.

PMID- 29209260
TI  - Awareness and Awakening: A Narrative-Oriented Inquiry of Undergraduate Students'
      Development of Mindful Agency in China.
AB  - The article explores undergraduate students' experiences of developing mindful
      agency as a positive learning disposition, their perceived change as a learner,
      and the possible impact of mindful agency coaching on students' learning and
      personal growth, using a narrative research method. Seventy Chinese undergraduate
      students generated personal reflective journals and eight participants' journals
      were selected to enter into the narrative-oriented inquiry. Our analysis revealed
      a number of primary themes based on which we produced a meta-story. The
      supplements of the story were exacted for further critical cross-case discussion.
      The finding indicated that the multifaceted development of mindful agency
      involved learning methods, emotional regulation, strategic thinking, and
      awareness of planning, openness to experience, self-acceptance and self-esteem,
      and learning engagement, with enhanced sense of personal awareness and awakening.
      The coaching was supportive for students to foster positive self-identities and
      become more reflective, mindful, and self-determined.

PMID- 29209261
TI  - Do True and False Intentions Differ in Level of Abstraction? A Test of Construal
      Level Theory in Deception Contexts.
AB  - The aim was to examine how people mentally represent alleged future actions-their
      true and false intentions. In two experiments, participants were asked to either
      tell the truth (i.e., express true intentions) or lie (i.e., express false
      intentions) about performing future tasks. Drawing on Construal Level Theory,
      which proposes that psychologically distant events are more abstractly construed
      than proximal ones, it was predicted that liars would have more abstract mental
      representations of the future tasks than truth tellers, due to differences in
      hypotheticality (i.e., the likelihood of the future tasks occurring). Construal
      level was measured by a video segmentation task (Experiment 1, N = 125) and
      preference for abstract or concrete descriptions of tasks (Experiment 2, N = 59).
      Veracity had no effect on construal level. Speaking against our initial
      predictions, the data indicate that true and false intentions are construed at
      similar levels of abstraction. The results are discussed in the light of
      Construal Level Theory and the emerging psycho-legal research on true and false
      intentions.

PMID- 29209259
TI  - Reinforcement Learning in Autism Spectrum Disorder.
AB  - Early behavioral interventions are recognized as integral to standard care in
      autism spectrum disorder (ASD), and often focus on reinforcing desired behaviors
      (e.g., eye contact) and reducing the presence of atypical behaviors (e.g.,
      echoing others' phrases). However, efficacy of these programs is mixed.
      Reinforcement learning relies on neurocircuitry that has been reported to be
      atypical in ASD: prefrontal-sub-cortical circuits, amygdala, brainstem, and
      cerebellum. Thus, early behavioral interventions rely on neurocircuitry that may
      function atypically in at least a subset of individuals with ASD. Recent work has
      investigated physiological, behavioral, and neural responses to reinforcers to
      uncover differences in motivation and learning in ASD. We will synthesize this
      work to identify promising avenues for future research that ultimately can be
      used to enhance the efficacy of early intervention.

PMID- 29209262
TI  - Body Size Estimation from Early to Middle Childhood: Stability of
      Underestimation, BMI, and Gender Effects.
AB  - Individuals who are overweight are more likely to underestimate their body size
      than those who are normal weight, and overweight underestimators are less likely
      to engage in weight loss efforts. Underestimation of body size might represent a
      barrier to prevention and treatment of overweight; thus insight in how
      underestimation of body size develops and tracks through the childhood years is
      needed. The aim of the present study was therefore to examine stability in
      children's underestimation of body size, exploring predictors of underestimation
      over time. The prospective path from underestimation to BMI was also tested. In a
      Norwegian cohort of 6 year olds, followed up at ages 8 and 10 (analysis sample: n
      = 793) body size estimation was captured by the Children's Body Image Scale,
      height and weight were measured and BMI calculated. Overall, children were more
      likely to underestimate than overestimate their body size. Individual stability
      in underestimation was modest, but significant. Higher BMI predicted future
      underestimation, even when previous underestimation was adjusted for, but there
      was no evidence for the opposite direction of influence. Boys were more likely
      than girls to underestimate their body size at ages 8 and 10 (age 8: 38.0% vs.
      24.1%; Age 10: 57.9% vs. 30.8%) and showed a steeper increase in underestimation
      with age compared to girls. In conclusion, the majority of 6, 8, and 10-year olds
      correctly estimate their body size (prevalence ranging from 40 to 70% depending
      on age and gender), although a substantial portion perceived themselves to be
      thinner than they actually were. Higher BMI forecasted future underestimation,
      but underestimation did not increase the risk for excessive weight gain in middle
      childhood.

PMID- 29209264
TI  - Evaluation of a Picture-Based Test for the Assessment of Gelotophobia.
AB  - This study examines whether coding open answers in a picture-based test, as to
      the extent they reflect the fear of being laughed at (i.e., gelotophobia),
      demonstrates sufficient validity to construct a semi-projective test for the
      assessment of gelotophobia. Previous findings indicate that cartoon stimuli
      depicting laughter situations (i.e., in the pilot version of the Picture-Geloph;
      Ruch et al., 2009) on average elicit fear-typical responses in gelotophobes
      stronger than in non-gelotophobes. The present study aims to (a) develop a
      standardized scoring procedure based on a coding scheme, and (b) examine the
      properties of the pilot version of the Picture-Geloph in order to select the most
      acceptable items for a standard form of the test. For Study 1, a sample of N =
      126 adults, with scores evenly distributed across the gelotophobia spectrum,
      completed the pilot version of the Picture-Geloph by noting down what they
      assumed the protagonist in each of 20 cartoons would say or think. Furthermore,
      participants answered the GELOPH<15> (Ruch and Proyer, 2008), the established
      questionnaire for the subjective assessment of the fear of being laughed at.
      Agreement between two independent raters indicated that the developed coding
      scheme allows for objective and reliable scoring of the Picture-Geloph (mean of
      intraclass correlations = 0.66). Nine items met the criteria employed to identify
      the psychometrically most reliable and valid items. These items were
      unidimensional and internally consistent (Cronbach's alpha = 0.78). The total
      score of this selection (i.e., the Picture-Geloph<9>) discriminated significantly
      between non-fearful, slightly, markedly, and extremely fearful individuals;
      furthermore, it correlated sufficiently high (r = 0.66; rc = 0.79 when corrected
      for reliability of both measures) with the GELOPH<15>. Cronbach's alpha (0.73)
      was largely comparable whereas the estimate of convergent validity was found to
      be lower in one (r = 0.50; rc = 0.61; N = 103) of the two samples in Study 2.
      Combining all three samples (N = 313) yielded a linear relationship between the
      self-report and the Picture-Geloph. With the Picture-Geloph<9> and the developed
      coding scheme, an unobtrusive and valid alternative instrument for the assessment
      of gelotophobia is provided. Possible applications are discussed.

PMID- 29209263
TI  - Changes in White-Matter Connectivity in Late Second Language Learners: Evidence
      from Diffusion Tensor Imaging.
AB  - Morphological brain changes as a consequence of new learning have been widely
      established. Learning a second language (L2) is one such experience that can lead
      to rapid structural neural changes. However, still relatively little is known
      about how levels of proficiency in the L2 and the age at which the L2 is learned
      influence brain neuroplasticity. The goal of this study is to provide novel
      evidence for the effect of bilingualism on white matter structure in relatively
      proficient but late L2 learners who acquired the second language after early
      childhood. Overall, the results demonstrate a significant effect on white matter
      fractional anisotropy (FA) as a function of L2 learning. Higher FA values were
      found in a broad white matter network including the anterior thalamic radiation
      (ATR), the inferior fronto-occipital fasciculus (IFOF), the Uncinate Fasciculus
      (UF), and the inferior longitudinal fasciculus (ILF). Moreover, FA values were
      correlated with age of L2 acquisition, suggesting that learning an L2, even past
      childhood, induces neural changes. Finally, these results provide some initial
      evidence that variability in the age of L2 acquisition has important consequences
      for neural plasticity.

PMID- 29209265
TI  - Working Conditions and Individual Differences Are Weakly Associated with
      Workaholism: A 2-3-Year Prospective Study of Shift-Working Nurses.
AB  - This study focuses on individual differences and the demand-support-control model
      in relation to workaholism. We hypothesized that unfavorable working conditions
      (high job demands, low job control/decision latitude, and low social support at
      work) and individual differences concerning sleep/wake-related variables (high
      flexibility, high morningness, and low languidity) would be related to
      workaholism measured 2-3 years later. Survey data stemmed from a prospective
      cohort of shift-working nurses (N = 1,308). The results showed that social
      support at work was negatively related to workaholism, whereas job demands were
      positively related to workaholism. Flexibility in terms of time for
      working/sleeping was also positively related to workaholism. The analyses further
      revealed that workaholism was inversely associated with age as well as having a
      child or having a child move in. Conjointly, the independent variables explained
      6.4% of the variance in workaholism, while their relative importance was small
      overall. After controlling for all other independent variables, high job demands
      had the strongest relationship (small-to-medium) with workaholism. This implies
      that less pressure from the external environment to work excessively hard may
      prevent an increase in workaholic behaviors. Overall, the study adds to our
      understanding of the relationships between working conditions, individual
      differences, and workaholism.

PMID- 29209267
TI  - Transition from Acute to Chronic Tinnitus: Predictors for the Development of
      Chronic Distressing Tinnitus.
AB  - Background: Acute tinnitus and its transition to chronic tinnitus are poorly
      investigated, and factors associated with amelioration versus exacerbation are
      largely unknown. Aims of this study were to identify early predictors for the
      future development of tinnitus severity. Method: Patients with tinnitus of no
      longer than 4 weeks presenting at an otolaryngologist filled out questionnaires
      at inclusion (T1), as well as 3 (T3), and 6 months (T4) after tinnitus onset. 6
      weeks after onset, an interview was conducted over the phone (T2). An audiogram
      was taken at T1, perceived tinnitus loudness, and tinnitus-related distress were
      assessed separately and repeatedly together with oversensitivity to external
      sounds and the levels of depression and anxiety. Furthermore, coping strategies
      with illness were recorded. Results: Complete remission until T4 was observed in
      11% of the 47 participants, while voiced complaints at onset were stable in the
      majority. In the subgroup with a relevant level of depression at T1, tinnitus
      related distress worsened in 30% until T4. For unilateral tinnitus, perceived
      loudness in the chronic condition correlated strongly with hearing loss at 2 kHz
      on the tinnitus ear, while a similar correlation was not found for tinnitus
      located to both ears or within the head. Conclusion: Results suggest early
      manifestation of tinnitus complaints, and stress the importance of screening all
      patients presenting with acute tinnitus for levels of depression and tinnitus
      related distress. Furthermore, hearing levels should be monitored, and use of
      hearing aids should be considered to reduce tinnitus loudness after having
      ascertained that sound sensitivity is within normal range.

PMID- 29209268
TI  - Implementation and Evaluation of an Economic Model for Telestroke: Experience
      from Virtuall, France.
AB  - Background: Telestroke is recognized as a safe and time-efficient way of treating
      stroke patients. However, admission centers (spokes) are subject to financial
      charges which can make them reluctant to join the system. We implemented and
      assessed an economic model supporting our telestroke system, Virtuall, France,
      which includes one expert center (hub) and six spokes. Methods: The model is
      based on payment for the expertise provided by the hub, distribution of charges
      related to telemedicine according to the fees perceived by the spokes, and
      transfer of patients between the spokes and the hub. We performed a cost-benefit
      analysis for all patients included in Virtuall from January 2014 to December 2015
      to assess the economic balance in each center. Results: 321 patients were
      prospectively included in the study. Application of the economic model resulted
      in overall financial balance with funding of a dedicated medical service in the
      hub, and reduced costs directly related to telestroke by an average of 10% in the
      spokes. The conditions generating the highest costs for the spokes were: a
      patient returning from the hub for re-hospitalization (mean cost of
      $1,995/patient); management of patients treated by intravenous thrombolysis
      without transfer to the hub (mean cost of $2,075/patient). The most favorable
      financial condition for the spokes remained simple transfer of patients to the
      hub and no return (mean cost of $329/patient). Conclusion: We describe an
      economic model which can be applied to any telestroke system to ensure the
      optimal balance between hub and spoke centers.

PMID- 29209266
TI  - Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic
      Brain Injury.
AB  - Traumatic brain injury (TBI) is a multidimensional and highly complex disease
      commonly resulting in widespread injury to axons, due to rapid inertial
      acceleration/deceleration forces transmitted to the brain during impact. Axonal
      injury leads to brain network dysfunction, significantly contributing to
      cognitive and functional impairments frequently observed in TBI survivors.
      Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of
      consciousness and coma on clinical examination and characterized by widespread
      injury to the hemispheric white matter tracts, the corpus callosum and the brain
      stem. The clinical course of DAI is commonly unpredictable and it remains a
      challenging entity with limited therapeutic options, to date. Although axonal
      integrity may be disrupted at impact, the majority of axonal pathology evolves
      over time, resulting from delayed activation of complex intracellular biochemical
      cascades. Activation of these secondary biochemical pathways may lead to axonal
      transection, named secondary axotomy, and be responsible for the clinical decline
      of DAI patients. Advances in the neurocritical care of TBI patients have been
      achieved by refinements in multimodality monitoring for prevention and early
      detection of secondary injury factors, which can be applied also to DAI. There is
      an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial
      fluid using microdialysis in the evaluation of axonal injury in TBI. These
      biomarker studies have assessed various axonal and neuroglial markers as well as
      inflammatory mediators, such as cytokines and chemokines. Moreover, modern
      neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI
      patients across all injury severities using magnetic resonance spectroscopy,
      diffusion tensor imaging, and positron emission tomography. Importantly, serial
      neuroimaging studies provide evidence for evolving axonal injury. Since axonal
      injury may be a key risk factor for neurodegeneration and dementias at long-term
      following TBI, the secondary injury processes may require prolonged monitoring.
      The aim of the present review is to summarize the clinical short- and long-term
      monitoring possibilities of axonal injury in TBI. Increased knowledge of the
      underlying pathophysiology achieved by advanced clinical monitoring raises hope
      for the development of novel treatment strategies for axonal injury in TBI.

PMID- 29209270
TI  - Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of
      Consciousness: Combined Behavioral and Event-Related Potential Evidence.
AB  - Background: The electrophysiological evidence supporting the therapeutic efficacy
      of multiple transcranial direct current stimulation (tDCS) sessions on
      consciousness improvement in patients with prolonged disorders of consciousness
      (DOCs) has not been firmly established. Objectives: To assess the effects of
      repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS
      R) score and event-related potential (ERP). Method: Using a sham-controlled
      randomized double-blind design, 26 patients were randomly assigned to either a
      real [five vegetative state (VS) and eight minimally conscious state (MCS)
      patients] or sham (six VS and seven MCS patients) stimulation group. The patients
      in the real stimulation group underwent 20 anodal tDCS sessions of the left
      dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS
      R score and P300 amplitude and latency in a hierarchical cognitive assessment
      were recorded to evaluate the consciousness level before tDCS and immediately
      after the 20 sessions. Results: The intra-group CRS-R analysis revealed a
      clinically significant improvement in the MCS patients in the real stimulation
      group. The inter-group CRS-R analysis showed a significant difference in CRS-R
      between VS and MCS patients at baseline in both the real and sham stimulation
      groups. The intra-group ERP analysis revealed a significant increase in P300
      amplitude after tDCS in the MCS patients in the real stimulation group, but no
      significant differences in P300 latency. For the inter-group ERP analysis, we
      observed significant differences regarding the presence of P300 at baseline
      between the VS and MCS patients in both groups. Conclusion: The repeated anodal
      tDCS of the left DLPFC could produce clinically significant improvements in MCS
      patients. The observed tDCS-related consciousness improvements might be related
      to improvements in attention resource allocation (reflected by the P300
      amplitude). The findings support the use of tDCS in clinical practice and ERP
      might serve as an efficient electrophysiological assessment tool in patients with
      DOCs.

PMID- 29209269
TI  - If Time Is Brain Where Is the Improvement in Prehospital Time after Stroke?
AB  - Despite the availability of thrombolytic and endovascular therapy for acute
      ischemic stroke, many patients are ineligible due to delayed hospital arrival.
      The identification of factors related to either early or delayed hospital arrival
      may reveal potential targets of intervention to reduce prehospital delay and
      improve access to time-critical thrombolysis and clot retrieval therapy. Here, we
      have reviewed studies reporting on factors associated with either early or
      delayed hospital arrival after stroke, together with an analysis of stroke onset
      to hospital arrival times. Much effort in the stroke treatment community has been
      devoted to reducing door-to-needle times with encouraging improvements. However,
      this review has revealed that the median onset-to-door times and the percentage
      of stroke patients arriving before the logistically critical 3 h have shown
      little improvement in the past two decades. Major factors affecting prehospital
      time were related to emergency medical pathways, stroke symptomatology, patient
      and bystander behavior, patient health characteristics, and stroke treatment
      awareness. Interventions addressing these factors may prove effective in reducing
      prehospital delay, allowing prompt diagnosis, which in turn may increase the
      rates and/or efficacy of acute treatments such as thrombolysis and clot retrieval
      therapy and thereby improve stroke outcomes.

PMID- 29209271
TI  - Development and Implementation of a New Telerehabilitation System for Audiovisual
      Stimulation Training in Hemianopia.
AB  - Telerehabilitation, defined as the method by which communication technologies are
      used to provide remote rehabilitation, although still underused, could be as
      efficient and effective as the conventional clinical rehabilitation practices. In
      the literature, there are descriptions of the use of telerehabilitation in adult
      patients with various diseases, whereas it is seldom used in clinical practice
      with child and adolescent patients. We have developed a new audiovisual
      telerehabilitation (AVT) system, based on the multisensory capabilities of the
      human brain, to provide a new tool for adults and children with visual field
      defects in order to improve ocular movements toward the blind hemifield. The
      apparatus consists of a semicircular structure in which visual and acoustic
      stimuli are positioned. A camera is integrated into the mechanical structure in
      the center of the panel to control eye and head movements. Patients can use this
      training system with a customized software on a tablet. From hospital, the
      therapist has complete control over the training process, and the results of the
      training sessions are automatically available within a few minutes on the
      hospital website. In this paper, we report the AVT system protocol and the
      preliminary results on its use by three adult patients. All three showed
      improvements in visual detection abilities with long-term effects. In the future,
      we will test this apparatus with children and their families. Since interventions
      for impairments in the visual field have a substantial cost for individuals and
      for the welfare system, we expect that our research could have a profound socio
      economic impact avoiding prolonged and intensive hospital stays.

PMID- 29209273
TI  - Updates on the Management of Advanced, Metastatic, and Radioiodine Refractory
      Differentiated Thyroid Cancer.
AB  - Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and
      is generally an indolent tumor, treated effectively with surgery, radioactive
      iodine, and thyroid-stimulating hormone suppressive therapy. However, 5-10% of
      patients have advanced disease, with aerodigestive tract invasion, distant
      metastases, or radioiodine refractory disease, with poor prognosis. This review
      focuses on the approaches for treating advanced DTC, including management of
      gross extra-thyroidal extension, recurrent loco-regional or distant metastatic
      disease, the role of external beam radiation therapy and systemic treatment.
      Locally ablative treatment modalities, including surgery, radiation therapy, and
      thermal ablation are evolving and can be used in selected patients. In recent
      years, new therapeutic agents with molecular targets have become available and
      two multi-kinase inhibitors, Sorafenib and Lenvatinib, have been licensed for
      iodine refractory DTC showing an advantage in terms of progression-free survival,
      although an impact on overall survival has not been proven yet. Management of
      advanced thyroid cancer can be challenging but a multidisciplinary approach can
      significantly improve outcomes for this patient population.

PMID- 29209272
TI  - A European Perspective on Auditory Processing Disorder-Current Knowledge and
      Future Research Focus.
AB  - Current notions of "hearing impairment," as reflected in clinical audiological
      practice, do not acknowledge the needs of individuals who have normal hearing
      pure tone sensitivity but who experience auditory processing difficulties in
      everyday life that are indexed by reduced performance in other more sophisticated
      audiometric tests such as speech audiometry in noise or complex non-speech sound
      perception. This disorder, defined as "Auditory Processing Disorder" (APD) or
      "Central Auditory Processing Disorder" is classified in the current tenth version
      of the International Classification of diseases as H93.25 and in the forthcoming
      beta eleventh version. APDs may have detrimental effects on the affected
      individual, with low esteem, anxiety, and depression, and symptoms may remain
      into adulthood. These disorders may interfere with learning per se and with
      communication, social, emotional, and academic-work aspects of life. The
      objective of the present paper is to define a baseline European APD consensus
      formulated by experienced clinicians and researchers in this specific field of
      human auditory science. A secondary aim is to identify issues that future
      research needs to address in order to further clarify the nature of APD and thus
      assist in optimum diagnosis and evidence-based management. This European
      consensus presents the main symptoms, conditions, and specific medical history
      elements that should lead to auditory processing evaluation. Consensus on
      definition of the disorder, optimum diagnostic pathway, and appropriate
      management are highlighted alongside a perspective on future research focus.

PMID- 29209274
TI  - Optimizing Patient Management and Adherence for Children Receiving Growth
      Hormone.
AB  - Poor adherence with growth hormone (GH) therapy has been associated with worse
      clinical outcomes, which in children relates specifically to their linear growth
      and loss of quality of life. The "360 degrees  GH in Europe" meeting, held in
      Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many
      aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and
      Referral," "Optimizing Patient Management," and "Managing Transition," each
      benefited from three guest speaker presentations, followed by an open discussion
      and are reported as a manuscript, authored by the speakers. Reported here is a
      summary of the proceedings of the second session, which reviewed the determinants
      of GH therapy response, factors affecting GH therapy adherence and the
      development of innovative technologies to improve GH treatment in children.
      Response to GH therapy varies widely, particularly in regard to the underlying
      diagnosis, although there is little consensus on the definition of a poor
      response. If the growth response is seen to be less than expected, the possible
      reasons should be discussed with patients and their parents, including compliance
      with the therapy regimen. Understanding and addressing the multiple factors that
      influence adherence, in order to optimize GH therapy, requires a multi
      disciplinary approach. Because therapy continues over many years, various
      healthcare professionals will be involved at different periods of the patient's
      journey. The role of the injection device for GH therapy, frequent monitoring of
      response, and patient support are all important for maintaining adherence. New
      injection devices are incorporating electronic technologies for automated
      monitoring and recording of clinically relevant information on injections. Study
      results are indicating that such devices can at least maintain GH adherence;
      however, acceptance of novel devices needs to be assessed and there remains an on
      going need for innovations.

PMID- 29209275
TI  - Lipid Uptake, Metabolism, and Transport in the Larval Zebrafish.
AB  - The developing zebrafish is a well-established model system for studies of energy
      metabolism, and is amenable to genetic, physiological, and biochemical
      approaches. For the first 5 days of life, nutrients are absorbed from its
      endogenous maternally deposited yolk. At 5 days post-fertilization, the yolk is
      exhausted and the larva has a functional digestive system including intestine,
      liver, gallbladder, pancreas, and intestinal microbiota. The transparency of the
      larval zebrafish, and the genetic and physiological similarity of its digestive
      system to that of mammals make it a promising system in which to address
      questions of energy homeostasis relevant to human health. For example,
      apolipoprotein expression and function is similar in zebrafish and mammals, and
      transgenic animals may be used to examine both the transport of lipid from yolk
      to body in the embryo, and the trafficking of dietary lipids in the larva.
      Additionally, despite the identification of many fatty acid and lipid transport
      proteins expressed by vertebrates, the cell biological processes that mediate the
      transport of dietary lipids from the intestinal lumen to the interior of
      enterocytes remain to be elucidated. Genetic tractability and amenability to live
      imaging and a range of biochemical methods make the larval zebrafish an ideal
      model in which to address open questions in the field of lipid transport, energy
      homeostasis, and nutrient metabolism.

PMID- 29209276
TI  - l-Thyroxine in an Oral Liquid or Softgel Formulation Ensures More Normal Serum
      Levels of Free T4 in Patients with Central Hypothyroidism.
AB  - Context: l-Thyroxine (l-T4) therapy of central hypothyroidism (CH) is guided by
      measurements of serum free thyroxine (FT4), which should be above the midnormal
      range value (MNRV). In some countries, novel formulations of oral l-T4 (liquid or
      softgel) are available further to the classic tablets. The intestinal absorption
      of either novel formulation is greater than tablets in patients with primary
      hypothyroidism. Objective: To evaluate whether new oral formulations of l-T4
      could be considered optimal in patients with CH who do not reach the FT4 target
      using tablet l-T4. Design: Our observation of six patients with isolated CH and
      serum FT4 below MNRV under stable adequate doses of tablet l-T4 (median 1.51
      MUg/kg bw/day), prompted us to switch them to liquid (n = 4) or softgel (n = 3) l
      T4 at the same dose, and verify whether FT4 increased above MNRV. A seventh
      patient with FT4 above MNRV was enrolled because she wanted a "more modern
      formulation." Postswitch FT4 was measured at least twice with the same kit as
      preswitch FT4. Results: In the first six patients, postswitch FT4 averaged 13.0
      +/- 1.6 pg/ml compared to 10.4 +/- 1.8 preswitch FT4 (P = 0.00026), with 11/13
      (85%) measurements above MNRV compared to 0/20. In the liquid or softgel l-T4
      group, postswitch FT4 averaged 13.1 +/- 1.6 vs. 10.6 +/- 0.9 pg/ml preswitch (P =
      0.0004) or 12.9 +/- 2.1 vs. 10.3 +/- 2.4 (P = 0.048), respectively. In the
      seventh patient (switched to liquid l-T4), averages were 18.3 vs. 15.2 pg/ml, and
      proportions 4/4 vs. 2/2. Conclusion: In CH patients, oral liquid or softgel l-T4
      administered at the same doses as tablet l-T4 ensures target serum FT4 levels
      above MNRV that tablet l-T4 may miss. In turn, this performance suggests the more
      favorable pharmacokinetics profile of either novel formulation compared with the
      tablet formulation.

PMID- 29209277
TI  - Exenatide Improves Bone Quality in a Murine Model of Genetically Inherited Type 2
      Diabetes Mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is associated with skeletal complications,
      including an increased risk of fractures. Reduced blood supply and bone strength
      may contribute to this skeletal fragility. We hypothesized that long-term
      administration of Exenatide, a glucagon-like peptide-1 receptor agonist, would
      improve bone architecture and strength of T2DM mice by increasing blood flow to
      bone, thereby stimulating bone formation. In this study, we used a model of
      obesity and severe T2DM, the leptin receptor-deficient db/db mouse to assess
      alterations in bone quality and hindlimb blood flow and to examine the beneficial
      effects of 4 weeks administration of Exenatide. As expected, diabetic mice showed
      marked alterations in bone structure, remodeling and strength, and basal vascular
      tone compared with lean mice. Exenatide treatment improved trabecular bone mass
      and architecture by increasing bone formation rate, but only in diabetic mice.
      Although there was no effect on hindlimb perfusion at the end of this treatment,
      Exenatide administration acutely increased tibial blood flow. While Exenatide
      treatment did not restore the impaired bone strength, intrinsic properties of the
      matrix, such as collagen maturity, were improved. The effects of Exenatide on in
      vitro bone formation were further investigated in primary osteoblasts cultured
      under high-glucose conditions, showing that Exenatide reversed the impairment in
      bone formation induced by glucose. In conclusion, Exenatide improves trabecular
      bone mass by increasing bone formation and could protect against the development
      of skeletal complications associated with T2DM.

PMID- 29209278
TI  - Follicle-Stimulating Hormone Regulates igfbp Gene Expression Directly or via
      Downstream Effectors to Modulate Igf3 Effects on Zebrafish Spermatogenesis.
AB  - Previous work showed that pharmacological inactivation of Igf-binding proteins
      (Igfbps), modulators of Igf activity, resulted in an excessive differentiation of
      type A undifferentiated (Aund) spermatogonia in zebrafish testis in tissue
      culture when Fsh was present in the incubation medium. Using this testis tissue
      culture system, we studied here the regulation of igfbp transcript levels by Fsh
      and two of its downstream effectors, Igf3 and 11-ketotestosterone (11-KT). We
      also explored how Fsh-modulated igfbp expression affected spermatogonial
      proliferation by adding or removing the Igfbp inhibitor NBI-31772 at different
      times. Fsh (100 ng/mL) decreased the transcript levels of igfbp1a, -3, and -6a
      after 1 or 3 days, while increasing igfbp2a and -5b expression, but only after 5
      days of incubation. Igf3 down-regulated the same igfbp transcripts as Fsh but
      with a delay of at least 4 days. 11-KT increased the transcripts (igfbp2a and 5b)
      that were elevated by Fsh and decreased those of igfbp6a, as did Fsh, while 11-KT
      did not change igfbp1a or -3 transcript levels. To evaluate Igfbps effects on
      spermatogenesis, we quantified under different conditions the mitotic indices and
      relative section areas occupied by the different spermatogonial generations (type
      Aund, type A differentiating (Adiff), or type B (B) spermatogonia). Igf3 (100
      ng/mL) increased the area occupied by Adiff and B while decreasing the one for
      Aund. Interestingly, a concentration of Igf3 that was inactive by itself (25
      ng/mL) became active in the presence of the Igfbp inhibitor NBI-31772 and
      mimicked the effect of 100 ng/mL Igf3 on spermatogonia. Studies exploiting the
      different dynamics of igfbp expression in response to Fsh and adding or removing
      NBI-31772 at different times showed that the quick downregulation of three igfbp
      as well as the delayed upregulated of two igfbps all support Igf3 bioactivity,
      namely the stimulation of spermatogonial differentiation. We conclude that Fsh
      modulates, directly or via androgens and Igf3, igfbp gene expression, supporting
      Igf3 bioactivity either by decreasing igfbp1a, -3, -6a or by increasing igfbp2a
      and -5b gene expression.

PMID- 29209280
TI  - Meloidogyne incognita Fatty Acid- and Retinol- Binding Protein (Mi-FAR-1) Affects
      Nematode Infection of Plant Roots and the Attachment of Pasteuria penetrans
      Endospores.
AB  - Root-knot nematode (RKN) Meloidogyne incognita is an economically important pest
      of crops. Pasteuria penetrans, is a nematode hyperparasitic bacterium capable of
      suppressing the reproduction of RKN and thereby useful for its management.
      Secreted fatty acid and retinol-binding proteins are unique in nematodes and are
      engaged in nutrient acquisition, development and reproduction; they are also a
      component of the nematode cuticle and thought to be involved in the interface
      between hosts and parasites. Attachment of endospores to the cuticle of second
      stage juveniles of RKN is the primary step of infection and several factors have
      been identified to facilitate attachment. In this study, the full length of Mi
      far-1 (573 bp) was cloned from M. incognita and characterized. Analysis revealed
      that the Mi-far-1 was rich in alpha-helix structure, contained a predicted
      consensus casein kinase II phosphorylation site and a glycosylation site.
      Quantitative PCR showed the highest expression in the fourth stage juveniles and
      in situ hybridization revealed the presence of Mi-far-1 mRNA in the hypodermis
      below the cuticle. Single copy insertion pattern of Mi-far-1 in M. incognita
      genome was detected by Southern blotting. Knockdown of Mi-far-1 showed
      significantly increased attachment of P. penetrans' endospores on juvenile
      cuticle surface and also affected host finding, root infection and nematode
      fecundity.

PMID- 29209279
TI  - Promoting Glucose Transporter-4 Vesicle Trafficking along Cytoskeletal Tracks:
      PAK-Ing Them Out.
AB  - Glucose is the principal cellular energy source in humans and maintenance of
      glucose homeostasis is critical for survival. Glucose uptake into peripheral
      skeletal muscle and adipose tissues requires the trafficking of vesicles
      containing glucose transporter-4 (GLUT4) from the intracellular storage
      compartments to the cell surface. Trafficking of GLUT4 storage vesicles is
      initiated via the canonical insulin signaling cascade in skeletal muscle and fat
      cells, as well as via exercise-induced contraction in muscle cells. Recent
      studies have elucidated steps in the signaling cascades that involve remodeling
      of the cytoskeleton, a process that underpins the mechanical movement of GLUT4
      vesicles. This review is focused upon an alternate phosphoinositide-3 kinase
      dependent pathway involving Ras-related C3 botulinum toxin substrate 1 signaling
      through the p21-activated kinase p21-activated kinase 1 and showcases related
      signaling events that co-regulate both the depolymerization and re-polymerization
      of filamentous actin. These new insights provide an enriched understanding into
      the process of glucose transport and yield potential new targets for
      interventions aimed to improve insulin sensitivity and remediate insulin
      resistance, pre-diabetes, and the progression to type 2 diabetes.

PMID- 29209282
TI  - Identification and Analysis of Novel Inhibitors against NS3 Helicase and NS5B RNA
      Dependent RNA Polymerase from Hepatitis C Virus 1b (Con1).
AB  - Hepatitis C virus (HCV) leads to severe liver diseases, including liver fibrosis,
      cirrhosis and hepatocellular carcinoma. Non-structural protein 3 helicase (NS3h)
      and non-structural protein 5B RNA-dependent RNA polymerase (NS5B) are involved in
      the replication of HCV RNA genome, and have been proved to be excellent targets
      for discovery of direct-acting antivirals. In this study, two high-throughput
      screening systems, fluorescence polarization (FP)-based ssDNA binding assay and
      fluorescence intensity (FI)-based dsRNA formation assay, were constructed to
      identify candidate NS3h and NS5B inhibitors, respectively. A library of
      approximately 800 small molecules and crude extracts, derived from marine
      microorganisms or purchased from the National Compound Resource Center, China,
      were screened, with three hits selected for further study. Natural compound
      No.3A5, isolated from marine fungi, inhibited NS3h activity with an IC50 value of
      2.8 MUM. We further demonstrated that compound No.3A5 inhibited the abilities of
      NS3h to bind ssDNA in electrophoretic mobility shift assay and to hydrolyze ATP.
      The NS3h-inhibitory activity of compound No.3A5 was reversible in our dilution
      assay, which indicated there was no stable NS3h-No.3A5 complex formed.
      Additionally, compound No.3A5 exhibited no binding selectivity on NS3h or single
      strand binding protein of Escherichia coli. In NS5B assays, commercial compounds
      No.39 and No.94 previously reported as kinase inhibitors were found to disrupt
      dsRNA formation, and their IC50 values were 62.9 and 18.8 MUM, respectively.
      These results highlight how identifying new uses for existing drugs is an
      effective method for discovering novel HCV inhibitors. To our knowledge, all
      inhibitors reported in this study were originally discovered with HCV anti-non
      structural protein activities in vitro.

PMID- 29209281
TI  - Nitrifier Gene Abundance and Diversity in Sediments Impacted by Acid Mine
      Drainage.
AB  - Extremely acidic and metal-rich acid mine drainage (AMD) waters can have severe
      toxicological effects on aquatic ecosystems. AMD has been shown to completely
      halt nitrification, which plays an important role in transferring nitrogen to
      higher organisms and in mitigating nitrogen pollution. We evaluated the gene
      abundance and diversity of nitrifying microbes in AMD-impacted sediments: ammonia
      oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and nitrite-oxidizing
      bacteria (NOB). Samples were collected from the Iron Springs Mining District
      (Ophir, CO, United States) during early and late summer in 2013 and 2014. Many of
      the sites were characterized by low pH (<5) and high metal concentrations.
      Sequence analyses revealed AOA genes related to Nitrososphaera, Nitrosotalea, and
      Nitrosoarchaeum; AOB genes related to Nitrosomonas and Nitrosospira; and NOB
      genes related to Nitrospira. The overall abundance of AOA, AOB and NOB was
      examined using quantitative PCR (qPCR) amplification of the amoA and nxrB
      functional genes and 16S rRNA genes. Gene copy numbers ranged from 3.2 * 104 -
      4.9 * 107 archaeal amoA copies * MUg DNA-1, 1.5 * 103 - 5.3 * 105 AOB 16S rRNA
      copies * MUg DNA-1, and 1.3 * 106 - 7.7 * 107Nitrospira nxrB copies * MUg DNA-1.
      Overall, Nitrospira nxrB genes were found to be more abundant than AOB 16S rRNA
      and archaeal amoA genes in most of the sample sites across 2013 and 2014. AOB 16S
      rRNA and Nitrospira nxrB genes were quantified in sediments with pH as low as
      3.2, and AOA amoA genes were quantified in sediments as low as 3.5. Though pH
      varied across all sites (pH 3.2-8.3), pH was not strongly correlated to the
      overall community structure or relative abundance of individual OTUs for any gene
      (based on CCA and Spearman correlations). pH was positivity correlated to the
      total abundance (qPCR) of AOB 16S rRNA genes, but not for any other genes. Metals
      were not correlated to the overall nitrifier community composition or abundance,
      but were correlated to the relative abundances of several individual OTUs. These
      findings extend our understanding of the distribution of nitrifying microbes in
      AMD-impacted systems and provide a platform for further research.

PMID- 29209283
TI  - Combination of Microfluidic Loop-Mediated Isothermal Amplification with Gold
      Nanoparticles for Rapid Detection of Salmonella spp. in Food Samples.
AB  - Foodborne diseases are an important cause of morbidity and mortality. According
      to the World Health Organization, there are 31 main global hazards, which caused
      in 2010 600 million foodborne illnesses and 420000 deaths. Among them, Salmonella
      spp. is one of the most important human pathogens, accounting for more than 90000
      cases in Europe and even more in the United States per year. In the current study
      we report the development, and thorough evaluation in food samples, of a
      microfluidic system combining loop-mediated isothermal amplification with gold
      nanoparticles (AuNPs). This system is intended for low-cost, in situ, detection
      of different pathogens, as the proposed methodology can be extrapolated to
      different microorganisms. A very low limit of detection (10 cfu/25 g) was
      obtained. Furthermore, the evaluation of spiked food samples (chicken, turkey,
      egg products), completely matched the expected results, as denoted by the index
      kappa of concordance (value of 1.00). The results obtained for the relative
      sensitivity, specificity and accuracy were of 100% as well as the positive and
      negative predictive values.

PMID- 29209284
TI  - The Sit-and-Wait Hypothesis in Bacterial Pathogens: A Theoretical Study of
      Durability and Virulence.
AB  - The intriguing sit-and-wait hypothesis predicts that bacterial durability in the
      external environment is positively correlated with their virulence. Since its
      first proposal in 1987, the hypothesis has been spurring debates in terms of its
      validity in the field of bacterial virulence. As a special case of the vector
      borne transmission versus virulence tradeoff, where vector is now replaced by
      environmental longevity, there are only sporadic studies over the last three
      decades showing that environmental durability is possibly linked with virulence.
      However, no systematic study of these works is currently available and
      epidemiological analysis has not been updated for the sit-and-wait hypothesis
      since the publication of Walther and Ewald's (2004) review. In this article, we
      put experimental evidence, epidemiological data and theoretical analysis together
      to support the sit-and-wait hypothesis. According to the epidemiological data in
      terms of gain and loss of virulence (+/-) and durability (+/-) phenotypes, we
      classify bacteria into four groups, which are: sit-and-wait pathogens (++),
      vector-borne pathogens (+-), obligate-intracellular bacteria (--), and free
      living bacteria (-+). After that, we dive into the abundant bacterial proteomic
      data with the assistance of bioinformatics techniques in order to investigate the
      two factors at molecular level thanks to the fast development of high-throughput
      sequencing technology. Sequences of durability-related genes sourced from Gene
      Ontology and UniProt databases and virulence factors collected from Virulence
      Factor Database are used to search 20 corresponding bacterial proteomes in batch
      mode for homologous sequences via the HMMER software package. Statistical
      analysis only identified a modest, and not statistically significant correlation
      between mortality and survival time for eight non-vector-borne bacteria with sit
      and-wait potentials. Meanwhile, through between-group comparisons, bacteria with
      higher host-mortality are significantly more durable in the external environment.
      The results of bioinformatics analysis correspond well with epidemiological data,
      that is, non-vector-borne pathogens with sit-and-wait potentials have higher
      number of virulence and durability genes compared with other bacterial groups.
      However, the conclusions are constrained by the relatively small bacterial sample
      size and non-standardized experimental data.

PMID- 29209285
TI  - Reduction of Salmonella Shedding by Sows during Gestation in Relation to Its
      Fecal Microbiome.
AB  - Pork meat is estimated to be responsible for 10-20% of human salmonellosis cases
      in Europe. Control strategies at the farm could reduce contamination at the
      slaughterhouse. One of the targeted sectors of production is maternity, where
      sows could be Salmonella reservoirs. The aim of this study was to assess the
      dynamics of shedding of Salmonella in terms of variation in both shedding
      prevalence and strains excreted during gestation in Quebec's maternity sector.
      The evolution of the fecal microbiota of these sows during gestation was also
      assessed to detect bacterial populations associated with these variations. A
      total of 73 sows both at the beginning and the end of the gestation were randomly
      selected and their fecal matter was analyzed. Salmonella detection was conducted
      using a method that includes two selective enrichment media (MSRV and TBG). Nine
      isolates per positive samples were collected. Among the 73 sows tested, 27 were
      shedding Salmonella. Sows in the first third of their gestation shed Salmonella
      significantly more frequently (21/27) than those in the last third (6/46) (chi2P
      < 0.05). The shedding status of 19 of the sows that were previously sampled in
      the first third of their gestation was followed, this time in the last third of
      their gestation, which confirmed reduction of shedding. Using 16S rRNA gene
      sequencing and qPCR, significant differences between the fecal flora of sows at
      the beginning and the end of the gestation, shedding Salmonella or not and with
      different parity number were detected. Using MaAsLin, multiple OTUs were found to
      be associated with the time of gestation, the status of Salmonella excretion and
      parity number. Some of the identified taxa could be linked to the reduction of
      the shedding of Salmonella at the end of gestation. In this study, we showed that
      the level of Salmonella shedding was variable during gestation with significantly
      higher shedding at the beginning rather than at the end of gestation. We also
      observed for the first time a significant change in the microbiota during sow
      gestation and identified interesting taxa which could be linked to a reduced
      Salmonella shedding.

PMID- 29209286
TI  - Differential Signaling and Sugar Exchanges in Response to Avirulent Pathogen- and
      Symbiont-Derived Molecules in Tobacco Cells.
AB  - Plants interact with microbes whose ultimate aim is to exploit plant
      carbohydrates for their reproduction. Plant-microbe interactions (PMIs) are
      classified according to the nature of their trophic exchanges: while mutualistic
      microbes trade nutrients with plants, pathogens unilaterally divert
      carbohydrates. The early responses following microbe recognition and the
      subsequent control of plant sugar distribution are still poorly understood. To
      further decipher PMI functionality, we used tobacco cells treated with microbial
      molecules mimicking pathogenic or mutualistic PMIs, namely cryptogein, a defense
      elicitor, and chitotetrasaccharide (CO4), which is secreted by mycorrhizal fungi.
      CO4 was perceived by tobacco cells and triggered widespread transient signaling
      components such as a sharp cytosolic Ca2+ elevation, NtrbohD-dependent H2O2
      production, and MAP kinase activation. These CO4-induced events differed from
      those induced by cryptogein, i.e., sustained events leading to cell death.
      Furthermore, cryptogein treatment inhibited glucose and sucrose uptake but not
      fructose uptake, and promoted the expression of NtSUT and NtSWEET sugar
      transporters, whereas CO4 had no effect on sugar uptake and only a slight effect
      on NtSWEET2B expression. Our results suggest that microbial molecules induce
      different signaling responses that reflect microbial lifestyle and the subsequent
      outcome of the interaction.

PMID- 29209287
TI  - ERM Proteins Play Distinct Roles in Cell Invasion by Extracellular Amastigotes of
      Trypanosoma cruzi.
AB  - The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas'
      disease. In mammalian hosts, T. cruzi alternates between trypomastigote and
      amastigote forms. Additionally, trypomastigotes can differentiate into
      amastigotes in the extracellular environment generating infective extracellular
      amastigotes (EAs). Ezrin-radixin-moesin (ERM) are key proteins linking plasma
      membrane to actin filaments, the major host cell component responsible for EA
      internalization. Our results revealed that depletion of host ezrin and radixin
      but not moesin inhibited EAs invasion in HeLa cells. ERM are recruited and
      colocalize with F-actin at EA invasion sites as shown by confocal microscopy.
      Invasion assays performed with cells overexpressing ERM showed increased EAs
      invasion in ezrin and radixin but not moesin overexpressing cells. Finally, time
      lapse experiments have shown altered actin dynamics leading to delayed EA
      internalization in ezrin and radixin depleted cells when compared to control or
      moesin depleted cells. Altogether, these findings show distinct roles of ERM
      during EAs invasion, possibly regulating F-actin dynamics and plasma membrane
      interplay.

PMID- 29209288
TI  - Antimicrobial Effects of Sulfonyl Derivative of 2(5H)-Furanone against Planktonic
      and Biofilm Associated Methicillin-Resistant and -Susceptible Staphylococcus
      aureus.
AB  - The gram-positive opportunistic bacterium Staphylococcus aureus is one of the
      most common causatives of a variety of diseases including skin and skin structure
      infection or nosocomial catheter-associated infections. The biofilm formation
      that is an important virulence factor of this microorganism renders the
      antibiotic therapy ineffective, because biofilm-embedded bacteria exhibit
      strongly increased tolerance to antimicrobials. Here, we describe a novel 3
      chloro-5(S)-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-4-[4
      methylphenylsulfonyl]-2(5H)-furanone (F105), possessing a sulfonyl group and l
      menthol moiety. Minimal inhibitory and bactericidal concentration values (MIC and
      MBC) of F105 were 10 and 40 mg/L, respectively, suggesting F105 biocidal
      properties. F105 exhibits pronounced activity against biofilm-embedded S. aureus
      and increases the efficacy of aminoglycosides (amikacin, gentamicin, and
      kanamycin) and benzalkonium chloride with fractional inhibitory concentration
      index values of 0.33-0.44 and 0.29, respectively, suggesting an alternative
      external treatment option, e.g., for wound infections. Moreover, low
      concentrations (0.5-1.3 mg/L) of F105 reduced the MICs of these antimicrobials
      twofold. By using confocal laser scanning microscopy and CFU counting, we show
      explicitly that F105 also restores the antimicrobial activity of gentamicin and
      ampicillin against S. aureus biofilms by several orders of magnitude. Biofilm
      structures were not destroyed but sterilized, with embedded cells being almost
      completely killed at twofold MBC. While F105 is quite toxic (CC50/MBC ratio 0.2),
      our data suggest that the F105 chemotype might be a promising starting point for
      the development of complex topical agents for combined anti-staphylococcal
      biofilm-therapies restoring the efficacy of some antibiotics against difficult to
      treat S. aureus biofilm.

PMID- 29209289
TI  - Co-existence of Rhizobia and Diverse Non-rhizobial Bacteria in the Rhizosphere
      and Nodules of Dalbergia odorifera Seedlings Inoculated with Bradyrhizobium
      elkanii, Rhizobium multihospitium-Like and Burkholderia pyrrocinia-Like Strains.
AB  - Rhizobia induce root nodules and fix atmospheric N2 for most legume species in
      exchange for carbon. However, the diverse endophytic non-rhizobial bacteria in
      legume nodules that co-exist with rhizobia are often ignored because they are
      difficult to cultivate using routine cultivation approaches. To enhance our
      understanding of the incidence and diversity of legume-bacteria associations, a
      high-throughput sequencing analysis of bacterial 16S rRNA genes was used to
      examine the bacterial community in the rhizospheres and root nodules of Dalbergia
      odorifera seedlings that were uninoculated or inoculated with Bradyrhizobium
      elkanii H255, Rhizobium multihospitium-like HT221, or Burkholderia pyrrocinia
      like H022238, in two growth media (nitrogen [N]-supplied soil or N-omitted
      potting mix). Seedlings inoculated with Bradyrhizobium had significantly more
      nodules than seedlings in the other inoculation conditions, regardless of growth
      media. Using the 15N natural abundance method, it was shown that the inoculated
      plants had significantly higher N2 fixation efficiency (48-57%) and specific
      nodule activity [269-313 MUg N mg-1 of dry weight (dwt) nodule] compared to the
      uninoculated plants (203 MUg N mg-1 dwt nodule). The 16S rRNA gene analysis
      showed that there was generally a higher bacterial diversity in the rhizosphere
      than in the nodules in the corresponding condition. Both rhizobial inoculation
      and media status significantly altered the bacterial communities in the
      rhizospheres and nodules (P < 0.05), with the exception of the inoculated soil
      rhizospheres. Regarding non-rhizobial bacteria, three genera, i.e., Lactococcus,
      Bacillus, and Pseudomonas, were consistently enriched in the rhizosphere and
      Bradyrhizobium, Chloroplast norank (which belongs to Cyanobacteria), and
      Lactococcus were commonly found in the nodules. In contrast, common rhizobial
      genera (including Rhizobium, Mesorhizobium, and Burkholderia) were only present
      in the nodules at low relative abundances (0.01-3.41%). Regarding non-rhizobial
      bacteria, 32 genera were found in the nodules, with non-rhizobial bacteria being
      predominant in the N omitted potting mix (with a relative abundance of 56-87%).
      This study suggests that legume nodules are inhabited by a high diversity of non
      rhizobial bacteria, which may play a vital role in nodulation and N2 fixation in
      the host plants.

PMID- 29209290
TI  - Enterotoxigenicity and Antimicrobial Resistance of Staphylococcus aureus Isolated
      from Retail Food in China.
AB  - Staphylococcus aureus is one of the most common causes of zoonotic agent in the
      world, which are attributable to the contamination of food with enterotoxins. In
      this study, a total of 1,150 S. aureus isolates were cultured from 27,000 retail
      foods items from 203 cities of 24 provinces in China in 2015 and were test for
      antimicrobial susceptibility. Additionally, the role of the genes responsible for
      the staphylococcal enterotoxins (SEA to SEE), methicillin resistance (mecA) and
      the toxigenic capabilities were also assessed. The results showed that 4.3%
      retail foods were contaminated with S. aureus, and 7.9% retail foods isolates
      were mecA positive. Some 97.6% of S. aureus isolates were resistant to at least
      one antimicrobial compound, and 57.5% of these were multi drug resistant (MDR).
      Resistance to penicillin (83.7%, 963/1,150), was common, followed by linezolid
      (67.7%, 778/1,150) and erythromycin (52.1%, 599/1,150). The isolates cultured
      from raw meats showed high levels of resistant to tetracycline (42.8%),
      ciprofloxacin (17.4%), and chloramphenicol (12.0%) and expressed a MDR phenotype
      (62.4%). A total of 29.7% S. aureus isolates harbored the classical SEs genes
      (sea, seb, sec, and sed). The sea and seb genes were the most frequent SEs genes
      detected. Of note, 22% of the SEs genes positive S. aureus harbored two or three
      SEs genes, and 16 isolates were confirmed with the capacity to simultaneously
      produce two or three enterotoxin types. Moreover, nearly 50% of the MRSA isolates
      were positive for at least one SE gene in this study. Therefore, it is important
      to monitor the antimicrobial susceptibility and enterotoxigenicity of MDR S.
      aureus and MRSA in the food chain and to use these data to develop food safety
      measures, designed to reduce the contamination and transmission of this
      bacterium.

PMID- 29209291
TI  - Essential APSES Transcription Factors for Mycotoxin Synthesis, Fungal
      Development, and Pathogenicity in Aspergillus flavus.
AB  - Aflatoxins are a potent carcinogenic mycotoxin and has become a research model of
      fungal secondary metabolism (SM). Via systematically investigating the APSES
      transcription factors (TFs), two APSES proteins were identified: AfRafA and
      AfStuA. These play central roles in the synthesis of mycotoxins including
      aflatoxin and cyclopiazonic acid, and fungal development and are consequently
      central to the pathogenicity of the aflatoxigenic A. flavus. Loss of AfRafA not
      only dramatically suppressed aflatoxin cluster expression, subsequently reducing
      toxin synthesis both in vitro and in vivo, but also impaired conidia and
      sclerotia development. More importantly, aflatoxin biosynthesis as well as
      conidia and sclerotia development were fully blocked in DeltaAfStuA. In addition,
      our results supported that AfStuA regulated the aflatoxin synthesis in an AflR
      dependent manner. Intriguingly, it was revealed that AfRafA and AfStuA exert an
      antagonistic role in the regulation of biosynthesis of cyclopiazonic acid. In
      summary, two global transcriptional regulators for fungal development, mycotoxin
      production, and seed pathogenicity of the A. flavus system have been established.
      The two novel regulators of mycotoxins are promising targets for future plant
      breeding and for the development of fungicides.

PMID- 29209292
TI  - Characterization of Colistin-Resistant Escherichia coli Isolated from Diseased
      Pigs in France.
AB  - We studied a collection of 79 colistin-resistant Escherichia coli isolates
      isolated from diseased pigs in France between 2009 and 2013. We determined a
      number of phenotypic and genetic characters using broth microdilution to
      characterize their antimicrobial susceptibility. We performed pulse field gel
      electrophoresis (PFGE) to assess their genetic diversity and assign them to
      phylogroups. High-throughput real-time PCR micro-array was used to screen for a
      selection of genetic markers of virulence, and PCR and sequencing of the main
      recognized resistance genes allowed us to investigate the mechanisms of colistin
      resistance. Results showed that isolates belonged to several phylogroups and most
      had a unique PFGE profile. More than 50% of the isolates were also resistant to
      sulfonamides, trimethoprim, tetracycline, ampicillin or chloramphenicol. The mcr
      1 gene was detected in 70 out of 79 isolates and was transferred by conjugation
      in 33 of them, sometimes together with resistance to sulfonamides, trimethoprim,
      tetracycline, ampicillin, chloramphenicol, cefotaxime, or gentamicin. Mutations
      in the amino-acid sequences of proteins MgrB, PhoP, PhoQ, PmrB, but not PmrA,
      were detected in isolates with or without the mcr-1 gene. More than one-third of
      the isolates harbored the F18, F4, astA, hlyA, estI, estII, elt, stx2e, iha,
      orfA, orfB, paa, terE, ecs1763, or ureD virulence markers. In conclusion,
      although most isolates had a unique PFGE profile, a few particular combinations
      of phylogenetic groups, virulence genes and mutations in the sequenced genes
      involved in colistin resistance were identified on a number of occasions,
      suggesting the persistence of certain isolates over several years.

PMID- 29209293
TI  - Dextransucrase Expression Is Concomitant with that of Replication and Maintenance
      Functions of the pMN1 Plasmid in Lactobacillus sakei MN1.
AB  - The exopolysaccharide synthesized by Lactobacillus sakei MN1 is a dextran with
      antiviral and immunomodulatory properties of potential utility in aquaculture. In
      this work we have investigated the genetic basis of dextran production by this
      bacterium. Southern blot hybridization experiments demonstrated the plasmidic
      location of the dsrLS gene, which encodes the dextransucrase involved in dextran
      synthesis. DNA sequencing of the 11,126 kbp plasmid (pMN1) revealed that it
      belongs to a family which replicates by the theta mechanism, whose prototype is
      pUCL287. The plasmid comprises the origin of replication, repA, repB, and dsrLS
      genes, as well as seven open reading frames of uncharacterized function. Lb.
      sakei MN1 produces dextran when sucrose, but not glucose, is present in the
      growth medium. Therefore, plasmid copy number and stability, as well as dsrLS
      expression, were investigated in cultures grown in the presence of either sucrose
      or glucose. The results revealed that pMN1 is a stable low-copy-number plasmid in
      both conditions. Gene expression studies showed that dsrLS is constitutively
      expressed, irrespective of the carbon source present in the medium. Moreover,
      dsrLS is expressed from a monocistronic transcript as well as from a
      polycistronic repA-repB-orf1-dsrLS mRNA. To our knowledge, this is the first
      report of a plasmid-borne dextransucrase-encoding gene, as well as the first time
      that co-transcription of genes involved in plasmid maintenance and replication
      with a gene encoding an enzyme has been established.

PMID- 29209294
TI  - Evolutionarily Conserved nodE, nodO, T1SS, and Hydrogenase System in Rhizobia of
      Astragalus membranaceus and Caragana intermedia.
AB  - Mesorhizobium species are the main microsymbionts associated with the medicinal
      or sand-fixation plants Astragalus membranaceus and Caragana intermedia (AC) in
      temperate regions of China, while all the Mesorhizobium strains isolated from
      each of these plants could nodulate both of them. However, Rhizobium yanglingense
      strain CCBAU01603 could nodulate AC plants and it's a high efficiency symbiotic
      and competitive strain with Caragana. Therefore, the common features shared by
      these symbiotic rhizobia in genera of Mesorhizobium and Rhizobium still remained
      undiscovered. In order to study the genomic background influencing the host
      preference of these AC symbiotic strains, the whole genomes of two (M.
      silamurunense CCBAU01550, M. silamurunense CCBAU45272) and five representative
      strains (M. septentrionale CCBAU01583, M. amorphae CCBAU01570, M. caraganae
      CCBAU01502, M. temperatum CCBAU01399, and R. yanglingense CCBAU01603) originally
      isolated from AC plants were sequenced, respectively. As results, type III
      secretion systems (T3SS) of AC rhizobia evolved in an irregular pattern, while an
      evolutionarily specific region including nodE, nodO, T1SS, and a hydrogenase
      system was detected to be conserved in all these AC rhizobia. Moreover, nodO was
      verified to be prevalently distributed in other AC rhizobia and was presumed as a
      factor affecting the nodule formation process. In conclusion, this research
      interpreted the multifactorial features of the AC rhizobia that may be associated
      with their host specificity at cross-nodulation group, including nodE, nodZ, T1SS
      as the possible main determinants; and nodO, hydrogenase system, and T3SS as
      factors regulating the bacteroid formation or nitrogen fixation efficiency.

PMID- 29209295
TI  - Extractive Fermentation of Lactic Acid in Lactic Acid Bacteria Cultivation: A
      Review.
AB  - Lactic acid bacteria are industrially important microorganisms recognized for
      their fermentative ability mostly in their probiotic benefits as well as lactic
      acid production for various applications. Nevertheless, lactic acid fermentation
      often suffers end-product inhibition which decreases the cell growth rate. The
      inhibition of lactic acid is due to the solubility of the undissociated lactic
      acid within the cytoplasmic membrane and insolubility of dissociated lactate,
      which causes acidification of cytoplasm and failure of proton motive forces. This
      phenomenon influences the transmembrane pH gradient and decreases the amount of
      energy available for cell growth. In general, the restriction imposed by lactic
      acid on its fermentation can be avoided by extractive fermentation techniques,
      which can also be exploited for product recovery.

PMID- 29209296
TI  - Illumina-Based Analysis of Endophytic and Rhizosphere Bacterial Diversity of the
      Coastal Halophyte Messerschmidia sibirica.
AB  - Halophytes play important roles in coastal ecosystems. However, few reports have
      described bacterial communities related to halophytes, and the distribution
      patterns of these bacteria in different plant tissues have been rarely compared.
      This paper mainly studied the diversity and community structure of endophytic and
      rhizosphere (Rh) bacteria related to the halophyte Messerschmidia sibirica, a
      dominant species in the coastal zone of Shandong Peninsula, China. We collected
      leaf (Lf), stem (Sm), root (Rt), Rh, and bulk (Bl) control soil samples, and
      sequenced the V5-V7 region of the bacterial 16S rRNA gene using the Illumina
      HiSeq platform to identify bacterial communities originating from different plant
      habitats. We found that the bacterial richness and diversity in Rh were
      significantly higher than those in the leaves, Sm, and Rt, but lower than those
      of the Bl control soil. In total, 37 phyla and 438 genera were identified.
      Microbial-diversity analysis showed that Proteobacteria and Actinobacteria were
      the dominant phyla and that Pseudomonas, Bacillus, Sphingomonas, Streptomyces,
      Microbacterium, Rhizobium, and Nocardioides were the dominant genera. However,
      there were clear differences in community diversity and structure among the
      samples. Endophytic bacteria community in Lf, Sm, and Rt shared more similarity
      than those in Rh and Bl control soil. The numbers of operational taxonomic units
      exclusive to the Lf, stem, Rt, Rh, and Bl control soil samples were 51, 43, 122,
      139, and 922, respectively, implying habitat-specific patterns. Principal
      coordinate analysis demonstrated differences were apparent in the bacterial
      communities associated with habitats. On the whole, M. sibirica affected
      bacterial diversity and structured the bacterial community. This study provides
      insight into the complex microbial compositions of coastal halophytes.

PMID- 29209297
TI  - Cpk2, a Catalytic Subunit of Cyclic AMP-PKA, Regulates Growth and Pathogenesis in
      Rice Blast.
AB  - The cAMP-Protein Kinase A signaling, anchored on CpkA, is necessary for
      appressorium development and host penetration, but indispensable for infectious
      growth in Magnaporthe oryzae. In this study, we identified and characterized the
      gene encoding the second catalytic subunit, CPK2, whose expression was found to
      be lower compared to CPKA at various stages of pathogenic growth in M. oryzae.
      Deletion of CPK2 caused no alterations in vegetative growth, conidiation,
      appressorium formation, or pathogenicity. Surprisingly, the cpkADeltacpk2Delta
      double deletion strain displayed significant reduction in growth rate and
      conidiation compared to the single deletion mutants. Interestingly, loss of CPKA
      and CPK2 resulted in morphogenetic defects in germ tubes (with curled/wavy and
      serpentine growth pattern) on hydrophobic surfaces, and a complete failure to
      produce appressoria therein, thus suggesting an important role for CPK2-mediated
      cAMP-PKA in surface sensing and response pathway. CPKA promoter-driven expression
      of CPK2 partially suppressed the defects in host penetration and pathogenicity in
      the cpkADelta. Such ectopic CPK2 expressing strain successfully penetrated the
      rice leaves, but was unable to produce proper secondary invasive hyphae, thus
      underscoring the importance of CpkA in growth and differentiation in planta. The
      Cpk2-GFP localized to the nuclei and cytoplasmic vesicles in conidia and germ
      tubes. The Cpk2-GFP colocalized with CpkA-mCherry on vesicles in the cytosol, but
      such overlap was not evident in the nuclei. Our studies indicate that CpkA and
      Cpk2 share overlapping functions, but also play distinct roles during
      pathogenesis-associated signaling and morphogenesis in the rice blast fungus.

PMID- 29209298
TI  - The Gut Entomotype of Red Palm Weevil Rhynchophorus ferrugineus Olivier
      (Coleoptera: Dryophthoridae) and Their Effect on Host Nutrition Metabolism.
AB  - For invasive insects, the potential roles of gut microbiota in exploiting new
      food resources and spreading remain elusive. Red palm weevil (RPW), Rhynchophorus
      ferrugineus Olivier, is an invasive destructive pest which feeds on nutrient-poor
      tender tissues and has caused extensive mortality of palm trees. The microbes
      associated with insects can improve their nutrition assimilation. However,
      experimental evidence on the interactions between RPW and its gut microbiota is
      still absent. The aim of this study is to determine the dynamics changes and the
      bacterial entomotype in the RPW gut and its potential physiological roles. Here,
      we confirmed RPW harbors a complex gut microbiota mainly constituted by bacteria
      in the families Enterobacteriaceae, Lactobacillaceae, Entomoplasmataceae, and
      Streptococcaceae. RPW gut microbiota exhibited a highly stable microbial
      community with low variance in abundance across different life stages and host
      plants. Furthermore, the abundance of Enterobacteriaceae was markedly increased
      but that of Acetobacteraceae was reduced significantly after administration of
      antibiotics. Although no significant effects were found on the body weight gain
      of RPW larvae, these alterations dramatically decreased the concentration of
      hemolymph protein and glucose while that of hemolymph triglyceride increased. In
      the gut of wild-caught RPW larvae, seven bacterial species in the genera
      Klebsiella, Serratia, Enterobacter, and Citrobacter were shown to have an ability
      to degrade cellulose. Together, RPW accommodate a stable gut microbiota which can
      degrade plant polysaccharides and confer their host optimal adaptation to its
      environment by modulating its metabolism.

PMID- 29209299
TI  - Natural Antisense Transcripts at the Interface between Host Genome and Mobile
      Genetic Elements.
AB  - Non-coding RNAs are involved in epigenetic processes, playing a role in the
      regulation of gene expression at the transcriptional and post-transcriptional
      levels. A particular group of ncRNA are natural antisense transcripts (NATs);
      these are transcribed in the opposite direction to protein coding transcripts and
      are widespread in eukaryotes. Their abundance, evidence of phylogenetic
      conservation and an increasing number of well-characterized examples of antisense
      mediated gene regulation are indicative of essential biological roles of NATs.
      There is evidence to suggest that they interfere with their corresponding sense
      transcript to elicit concordant and discordant regulation. The main mechanisms
      involved include transcriptional interference as well as dsRNA formation. Sense
      antisense hybrid formation can trigger RNA interference, RNA editing or protein
      kinase R. However, the exact molecular mechanisms elicited by NATs in the context
      of these regulatory roles are currently poorly understood. Several examples
      confirm that ectopic expression of antisense transcripts trigger epigenetic
      silencing of the related sense transcript. Genomic approaches suggest that the
      antisense transcriptome carries a broader biological significance which goes
      beyond the physiological regulation of the directly related sense transcripts.
      Because NATs show evidence of conservation we speculate that they played a role
      in evolution, with early eukaryotes gaining selective advantage through the
      regulatory effects. With the surge of genome and transcriptome sequencing
      projects, there is promise of a more comprehensive understanding of the
      biological role of NATs and the regulatory mechanisms involved.

PMID- 29209300
TI  - Molecular Characteristics of ST1193 Clone among Phylogenetic Group B2 Non-ST131
      Fluoroquinolone-Resistant Escherichia coli.
AB  - Objectives: Sequence type 1193 is emerging as a new, virulent and resistant
      lineage among fluoroquinolone resistant Escherichia coli (FQrE. coli). In this
      study, we investigated the prevalence and molecular characteristics of this clone
      isolated from a Chinese university hospital. Methods: 73 phylogenetic group B2
      FQr-non-ST131 isolates were collected from August 2014 and August 2015 at a
      Chinese university hospital. Isolates were screened for ST1193 by multilocus
      sequence typing. E. coli ST1193 then underwent lactose fermentation
      determination, susceptibility testing, virulence genotyping, PCR-based O typing,
      pulsed-field gel electrophoresis (PFGE) and FQr mechanism analysis. Results: Of
      73 B2-FQr-non ST131 E. coli isolates, 69.9% (n = 51) were ST1193. 90.2% (46/51)
      of ST1193 isolates were O75 serotype and 96.1% (49/51) of the ST1193 isolates
      were lactose non-fermenters. 35 clusters were identified by PFGE. ST1193 isolates
      exhibited a set of 3 conserved mutations defining quinolone-resistance
      determining region substitutions (gyrA S83L, D87N, and parC S80I). The most
      frequent VF genes detected in these E. coli ST1193 isolates were fyuA
      (yersiniabactin, 96.1%), fimH (type 1 fimbriae, 94.1%), iutA (iron uptake gene,
      90.2%), kpsMT II (group II capsule, 90.2%), kpsK1 (K1 capsule, 86.3%) and PAI.
      Conclusion: ST1193 lineage accounts for the majority of group B2-FQr-non-ST131 E.
      coli clinical isolates. Most of the ST1193 are serotype O75 and lactose non
      fermenting. Strategic surveillance and control schemes are needed in the future
      for this newly emerging clone of E. coli: B2-FQr-ST1193.

PMID- 29209301
TI  - The Antifungal Plant Defensin HsAFP1 Is a Phosphatidic Acid-Interacting Peptide
      Inducing Membrane Permeabilization.
AB  - HsAFP1, a plant defensin isolated from coral bells (Heuchera sanguinea), is
      characterized by broad-spectrum antifungal activity. Previous studies indicated
      that HsAFP1 binds to specific fungal membrane components, which had hitherto not
      been identified, and induces mitochondrial dysfunction and cell membrane
      permeabilization. In this study, we show that HsAFP1 reversibly interacts with
      the membrane phospholipid phosphatidic acid (PA), which is a precursor for the
      biosynthesis of other phospholipids, and to a lesser extent with various
      phosphatidyl inositol phosphates (PtdInsP's). Moreover, via reverse ELISA assays
      we identified two basic amino acids in HsAFP1, namely histidine at position 32
      and arginine at position 52, as well as the phosphate group in PA as important
      features enabling this interaction. Using a HsAFP1 variant, lacking both amino
      acids (HsAFP1[H32A][R52A]), we showed that, as compared to the native peptide,
      the ability of this variant to bind to PA and PtdInsP's is reduced (>=74%) and
      the antifungal activity of the variant is reduced (>=2-fold), highlighting the
      link between PA/PtdInsP binding and antifungal activity. Using fluorescently
      labelled HsAFP1 in confocal microscopy and flow cytometry assays, we showed that
      HsAFP1 accumulates at the cell surface of yeast cells with intact membranes, most
      notably at the buds and septa. The resulting HsAFP1-induced membrane
      permeabilization is likely to occur after HsAFP1's internalization. These data
      provide novel mechanistic insights in the mode of action of the HsAFP1 plant
      defensin.

PMID- 29209302
TI  - Influence of Stress and Antibiotic Resistance on Cell-Length Distribution in
      Mycobacterium tuberculosis Clinical Isolates.
AB  - Mycobacterial cellular variations in growth and division increase heterogeneity
      in cell length, possibly contributing to cell-to-cell variation in host and
      antibiotic stress tolerance. This may be one of the factors influencing
      Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis (TB) is a
      major public health problem in developing countries, antibiotic persistence, and
      emergence of antibiotic resistance further complicates this problem. We wanted to
      investigate the factors influencing cell-length distribution in clinical M.
      tuberculosis strains. In parallel we examined M. tuberculosis cell-length
      distribution in a large set of clinical strains (n = 158) from ex vivo sputum
      samples, in vitro macrophage models, and in vitro cultures. Our aim was to
      understand the influence of clinically relevant factors such as host stresses, M.
      tuberculosis lineages, antibiotic resistance, antibiotic concentrations, and
      disease severity on the cell size distribution in clinical M. tuberculosis
      strains. Increased cell size and cell-to-cell variation in cell length were
      associated with bacteria in sputum and infected macrophages rather than liquid
      culture. Multidrug-resistant (MDR) strains displayed increased cell length
      heterogeneity compared to sensitive strains in infected macrophages and also
      during growth under rifampicin (RIF) treatment. Importantly, increased cell
      length was also associated with pulmonary TB disease severity. Supporting these
      findings, individual host stresses, such as oxidative stress and iron deficiency,
      increased cell-length heterogeneity of M. tuberculosis strains. In addition we
      also observed synergism between host stress and RIF treatment in increasing cell
      length in MDR-TB strains. This study has identified some clinical factors
      contributing to cell-length heterogeneity in clinical M. tuberculosis strains.
      The role of these cellular adaptations to host and antibiotic tolerance needs
      further investigation.

PMID- 29209303
TI  - pH Stress-Induced Cooperation between Rhodococcus ruber YYL and Bacillus cereus
      MLY1 in Biodegradation of Tetrahydrofuran.
AB  - Microbial consortia consisting of cooperational strains exhibit biodegradation
      performance superior to that of single microbial strains and improved remediation
      efficiency by relieving the environmental stress. Tetrahydrofuran (THF), a
      universal solvent widely used in chemical and pharmaceutical synthesis,
      significantly affects the environment. As a refractory pollutant, THF can be
      degraded by some microbial strains under suitable conditions. There are often a
      variety of stresses, especially pH stress, that inhibit the THF-degradation
      efficiency of microbial consortia. Therefore, it is necessary to study the
      molecular mechanisms of microbial cooperational degradation of THF. In this
      study, under conditions of low pH (initial pH = 7.0) stress, a synergistic
      promotion of the THF degradation capability of the strain Rhodococcus ruber YYL
      was found in the presence of a non-THF degrading strain Bacillus cereus MLY1.
      Metatranscriptome analysis revealed that the low pH stress induced the strain YYL
      to up-regulate the genes involved in anti-oxidation, mutation, steroid and bile
      acid metabolism, and translation, while simultaneously down-regulating the genes
      involved in ATP production. In the co-culture system, strain MLY1 provides fatty
      acids, ATP, and amino acids for strain YYL in response to low pH stress during
      THF degradation. In return, YYL shares the metabolic intermediates of THF with
      MLY1 as carbon sources. This study provides the preliminary mechanism to
      understand how microbial consortia improve the degradation efficiency of
      refractory furan pollutants under environmental stress conditions.

PMID- 29209304
TI  - Revisiting Antibiotic Resistance Spreading in Wastewater Treatment Plants -
      Bacteriophages as a Much Neglected Potential Transmission Vehicle.
AB  - The spread of antibiotic resistance is currently a major threat to health that
      humanity is facing today. Novel multidrug and pandrug resistant bacteria are
      reported on a yearly basis, while the development of novel antibiotics is
      lacking. Focus to limit the spread of antibiotic resistance by reducing the usage
      of antibiotics in health care, veterinary applications, and meat production, have
      been implemented, limiting the exposure of pathogens to antibiotics, thus
      lowering the selection of resistant strains. Despite these attempts, the global
      resistance has increased significantly. A recent area of focus has been to limit
      the spread of resistance through wastewater treatment plants (WWTPs), serving as
      huge reservoirs of microbes and resistance genes. While being able to quite
      efficiently reduce the presence of resistant bacteria entering any of the final
      products of WWTPs (e.g., effluent water and sludge), the presence of resistance
      genes in other formats (mobile genetic elements, bacteriophages) has mainly been
      ignored. Recent data stress the importance of transduction in WWTPs as a mediator
      of resistance spread. Here we examine the current literature in the role of WWTPs
      as reservoirs and hotspots of antibiotic resistance with a specific focus on
      bacteriophages as mediators of genetic exchange.

PMID- 29209305
TI  - Unveiling and Characterizing Early Bilateral Interactions between Biofilm and the
      Mouse Innate Immune System.
AB  - A very substantial progress has been made in our understanding of infectious
      diseases caused by invasive bacteria. Under their planktonic forms, bacteria
      transiently reside in the otherwise sterile mammal body tissues, as the
      physiological inflammation insures both their clearance and repair of any tissue
      damage. Yet, the bacteria prone to experience planktonic to biofilm developmental
      transition still need to be studied. Of note, sessile bacteria not only persist
      but also concur preventing the effectors and regulators of the physiological
      inflammation to operate. Thus, it is urgent to design biologically sound
      experimental approaches aimed to extract, at the earliest stage, immune
      signatures of mono-bacteria planktonic to biofilm developmental transition in
      vivo and ex vivo. Indeed, the transition is often the first event to which
      succeeds the "chronicization" process whereby classical bacteria-targeting
      therapies are no more efficacious. An in vivo model of micro-injection of
      Staphylococcus aureus planktonic or biofilm cells in the ear pinna dermis of
      laboratory transgenic mice with fluorescent immune cells is proposed. It allows
      visualizing, in real time, the range of the early interactions between the S.
      aureus and myeloid cell subsets- the resident macrophages and dendritic cells,
      the recruited neutrophil granulocytes/polymorphonuclear neutrophils, monocytes
      otherwise known to differentiate as macrophages or dendritic cells. One main
      objective is to extract contrasting immune signatures of the modulation of the
      physiological inflammation with respect to the two bacterial lifestyles.

PMID- 29209306
TI  - CTX-M-15-Producing E. coli Isolates from Food Products in Germany Are Mainly
      Associated with an IncF-Type Plasmid and Belong to Two Predominant Clonal E. coli
      Lineages.
AB  - Extended-spectrum beta-lactamases (ESBL) mediating resistance to 3rd generation
      cephalosporins are a major public health issue. As food may be a vehicle in the
      spread of ESLB-producing bacteria, a study on the occurrence of cephalosporin
      resistantu Escherichia coli in food was initiated. A total of 404 ESBL-producing
      isolates were obtained from animal-derived food samples (e.g., poultry products,
      pork, beef and raw milk) between 2011 and 2013. As CTX-M-15 is the most abundant
      enzyme in ESBL-producing E. coli causing human infections, this study focusses on
      E. coli isolates from food samples harboring the blaCTX-M-15 gene. The blaCTX-M
      15 gene was detected in 5.2% (n = 21) of all isolates. Molecular analyses
      revealed a phylogenetic group A ST167 clone that was repeatedly isolated from raw
      milk and beef samples over a period of 6 months. The analyses indicate that
      spread of CTX-M-15-producing E. coli in German food samples were associated with
      a multireplicon IncF (FIA FIB FII) plasmid and additional antimicrobial
      resistance genes such as aac(6)-Ib-cr, blaOXA-1, catB3, different tet-variants as
      well as a class 1 integron with an aadA5/dfrA17 gene cassette. In addition, four
      phylogenetic group A ST410 isolates were detected. Three of them carried a
      chromosomal copy of the blaCTX-M-15 gene and a single isolate with the gene on a
      90 kb IncF plasmid. The blaCTX-M-15 gene was always associated with the ISEcp1
      element. In conclusion, CTX-M-15-producing E. coli were detected in German food
      samples. Among isolates of different matrices, two prominent clonal lineages,
      namely A-ST167 and A-ST410, were identified. These lineages may be important for
      the foodborne dissemination of CTX-M-15-producing E. coli in Germany.
      Interestingly, these clonal lineages were reported to be widely distributed and
      especially prevalent in isolates from humans and livestock. Transmission of CTX-M
      15-harboring isolates from food-producing animals to food appears probable, as
      isolates obtained from livestock and food samples within the same time period
      exhibit comparable characteristics as compared to isolates detected from human.
      However, the routes and direction of transmission need further investigation.

PMID- 29209307
TI  - Editorial: Cross Talk between Lymph Node Lymphatic Endothelial Cells and T-Cells
      during Inflammation and Cancer.

PMID- 29209308
TI  - Program Cell Death Receptor-1-Mediated Invariant Natural Killer T-Cell Control of
      Peritoneal Macrophage Modulates Survival in Neonatal Sepsis.
AB  - We have shown that invariant natural killer T (iNKT) cells mediate sepsis-induced
      end-organ changes and immune responses, including macrophage bacterial
      phagocytosis, a finding regulated by the check point protein program cell death
      receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and
      neonatal murine sepsis as well as in surgical patients. Given our previous
      findings, we hypothesize that iNKT cells will also modulate neonatal sepsis
      survival, and that this effect is regulated in part through PD-1. We utilized a
      polymicrobial intra-peritoneal cecal slurry (CS) sepsis model in wild type (WT),
      iNKT-/- or PD-1-/- 5-7 day old neonatal pups. Typically, tissues were harvested
      at 24 h for various bioassays/histology and, in some cases, survival was assessed
      for up to 7 days. Interestingly, similar to what we recently reported for PD-1-/-
      mice following CS, iNKT-/--deficient animals exhibit a markedly improved survival
      vs. WT. Histologically, minor alterations in liver architectural, which were
      noted in WT pups, were attenuated in both iNKT-/- and PD-1-/- pups. Following CS,
      PECAM-1 expression was unchanged in the WT pups but increased in both iNKT-/- and
      PD-1-/- pups. In WT, following CS the emergence of a Ly6Clow subpopulation was
      noted among the influxed peritoneal macrophage population. Conversely, within
      iNKT-/- pups, there were fewer peritoneal macrophages and a greater percentage of
      Ly6Chigh macrophages. We show not only a key role for iNKT cells in affecting end
      organ damage as well as alterations in phagocytes phenotypes in neonatal sepsis
      but that this iNKT cell mediated effect is driven by the central checkpoint
      protein PD-1.

PMID- 29209309
TI  - New Directions for Natural Killer T Cells in the Immunotherapy of Cancer.
AB  - Natural killer T (NKT) cells have been placed at the interface between innate and
      adaptive immunity by a long series of experiments that convincingly showed that
      beyond cytokine secretion and NK cell recruitment, NKT cells were coordinating
      dendritic cell and B cell maturation through direct membrane contacts and
      initiate productive responses. As such, NKT cells are the cellular adjuvant of
      many immune reactions and have functions that go much beyond what their name
      encapsulates. In addition, the initial discovery of the ligands of NKT cells is
      deeply linked to cancer biology and therapy. However, for a host of reasons,
      animal models in which agonists of NKT cells were used did not translate well to
      human cancers. A systematic reassessment of NKT cells role in tumorigenesis,
      especially spontaneous one, is now accessible using single cell analysis
      technologies both in mouse and man, and should be taken advantage of. Similarly,
      the migration, localization, phenotype of NKT cells following induced expansion
      after injection of an agonist can be examined at the single cell level. This
      technological revolution will help evaluate where and how NKT cells can be used
      in cancer.

PMID- 29209310
TI  - Alum Activates the Bovine NLRP3 Inflammasome.
AB  - There has been a move away from vaccines composed of whole or inactivated
      antigens toward subunit-based vaccines, which although safe, provide less
      immunological protection. As a result, the use of adjuvants to enhance and direct
      adaptive immune responses has become the focus of much targeted bovine vaccine
      research. However, the mechanisms by which adjuvants work to enhance
      immunological protection in many cases remains unclear, although this knowledge
      is critical to the rational design of effective next generation vaccines. This
      study aimed to investigate the mechanisms by which alum, a commonly used adjuvant
      in bovine vaccines, enhances IL-1beta secretion in bovine peripheral blood
      mononuclear cells (PBMCs). Unlike the case with human PBMCs, alum promoted IL
      1beta secretion in a subset of bovine PBMCs without priming with a toll-like
      receptor agonist. This suggests that PBMCs from some cattle are primed to produce
      this potent inflammatory cytokine and western blotting confirmed the presence of
      preexisting pro-IL-1beta in PBMCs from a subset of 8-month-old cattle. To address
      the mechanism underlying alum-induced IL-1beta secretion, specific inhibitors
      identified that alum mediates lysosomal disruption which subsequently activates
      the assembly of an NLRP3, ASC, caspase-1, and potentially caspase-8 containing
      complex. These components form an inflammasome, which mediates alum-induced IL
      1beta secretion in bovine PBMCs. Given the demonstrated role of the NLRP3
      inflammasome in regulating adaptive immunity in murine systems, these results
      will inform further targeted research into the potential of inflammasome
      activation for rational vaccine design in cattle.

PMID- 29209312
TI  - Dual Molecular Mechanisms Govern Escape at Immunodominant HLA A2-Restricted HIV
      Epitope.
AB  - Serial accumulation of mutations to fixation in the SLYNTVATL (SL9)
      immunodominant, HIV p17 Gag-derived, HLA A2-restricted cytotoxic T lymphocyte
      epitope produce the SLFNTIAVL triple mutant "ultimate" escape variant. These
      mutations in solvent-exposed residues are believed to interfere with TCR
      recognition, although confirmation has awaited structural verification. Here, we
      solved a TCR co-complex structure with SL9 and the triple escape mutant to
      determine the mechanism of immune escape in this eminent system. We show that, in
      contrast to prevailing hypotheses, the main TCR contact residue is 4N and the
      dominant mechanism of escape is not via lack of TCR engagement. Instead, mutation
      of solvent-exposed residues in the peptide destabilise the peptide-HLA and reduce
      peptide density at the cell surface. These results highlight the extraordinary
      lengths that HIV employs to evade detection by high-affinity TCRs with a broad
      peptide-binding footprint and necessitate re-evaluation of this exemplar model of
      HIV TCR escape.

PMID- 29209311
TI  - Codevelopment of Microbiota and Innate Immunity and the Risk for Group B
      Streptococcal Disease.
AB  - The pathogenesis of neonatal late-onset sepsis (LOD), which manifests between the
      third day and the third month of life, remains poorly understood. Group B
      Streptococcus (GBS) is the most important cause of LOD in infants without
      underlying diseases or prematurity and the third most frequent cause of
      meningitis in the Western world. On the other hand, GBS is a common intestinal
      colonizer in infants. Accordingly, despite its adaption to the human lower
      gastrointestinal tract, GBS has retained its potential virulence and its
      transition from a commensal to a dangerous pathogen is unpredictable in the
      individual. Several cellular innate immune mechanisms, in particular Toll-like
      receptors, the inflammasome and the cGAS pathway, are engaged by GBS effectors
      like nucleic acids. These are likely to impact on the GBS-specific host
      resistance. Given the long evolution of streptococci as a normal constituent of
      the human microbiota, the emergence of GBS as the dominant neonatal sepsis cause
      just about 50 years ago is remarkable. It appears that intensive usage of
      tetracycline starting in the 1940s has been a selection advantage for the
      currently dominant GBS clones with superior adhesive and invasive properties. The
      historical replacement of Group A by Group B streptococci as a leading neonatal
      pathogen and the higher frequency of other beta-hemolytic streptococci in areas
      with low GBS prevalence suggests the existence of a confined streptococcal niche,
      where locally competing streptococcal species are subject to environmental and
      immunological selection pressure. Thus, it seems pivotal to resolve neonatal
      innate immunity at mucous surfaces and its impact on microbiome composition and
      quality, i.e., genetic heterogeneity and metabolism, at the microanatomical
      level. Then, designer pro- and prebiotics, such as attenuated strains of GBS, and
      oligonucleotide priming of mucosal immunity may unfold their potential and
      facilitate adaptation of potentially hazardous streptococci as part of a
      beneficial local microbiome, which is stabilized by mucocutaneous innate
      immunity.

PMID- 29209314
TI  - Probiotic Strain Lactobacillus casei BL23 Prevents Colitis-Associated Colorectal
      Cancer.
AB  - The gut microbiota plays a major role in intestinal health, and an imbalance in
      its composition can lead to chronic gut inflammation and a predisposition to
      developing colorectal cancer (CRC). Currently, the use of probiotic bacteria
      represents an emerging alternative to treat and prevent cancer. Moreover,
      consumption of these beneficial bacteria may also favorably modulate the
      composition of the gut microbiota, which has been described in several studies to
      play an important role in CRC carcinogenesis. In this context, the aim of this
      study was to assess the protective effect of oral treatment with Lactobacillus
      casei BL23, a probiotic strain well known for its anti-inflammatory and
      anticancer properties. First, CRC was induced in C57BL6 mice by a single
      intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses
      of dextran sodium sulfate (2.5%) in drinking water that were separated by an
      adjustable recovery period. At the time of sacrifice (day 46), tumor incidence,
      histological scores, and epithelial proliferation were determined in colon
      samples. Our results show that L. casei BL23 significantly protected mice against
      CRC development; specifically, L. casei BL23 treatment reduced histological
      scores and proliferative index values. In addition, our analysis revealed that L.
      casei BL23 had an immunomodulatory effect, mediated through the downregulation of
      the IL-22 cytokine, and an antiproliferative effect, mediated through the
      upregulation of caspase-7, caspase-9, and Bik. Finally, L. casei BL23 treatment
      tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an
      analysis of fecal microbiota. Altogether our results demonstrate the high
      potential of L. casei BL23 for the development of new, probiotic-based strategies
      to fight CRC.

PMID- 29209313
TI  - Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice
      Infected with Trypanosoma cruzi.
AB  - Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin
      America but has become a global public health concern by migration of infected
      people. It has been reported that parasite persistence as well as the intensity
      of the inflammatory immune response are determinants of the clinical
      manifestations of the disease. Even though inflammation is indispensable for host
      defense, when deregulated, it can contribute to tissue injury and organ
      dysfunction. Here, we report the importance of B cells in conditioning T cell
      response in T. cruzi infection. Mice deficient in mature B cells (muMT mice)
      infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF
      producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells
      was accompanied by a reduction in IFNgamma+CD4+ T cells and a decrease of the
      frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The
      CD4+ T cell population activated by T. cruzi infection, in absence of mature B
      cells, had a high frequency of Ly6C+ cells and showed a lower expression of
      inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected
      muMT mice presented a high frequency of CD62LhiCD44- cells, which is commonly
      associated with a naive phenotype. Through transfer experiments we demonstrated
      that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells
      response from infected wild-type mice. Interestingly, using Blimp-flox/flox
      CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi
      infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our
      results showed that the absence of B cells during T. cruzi infection affected the
      T cell response at different levels and generated a favorable scenario for
      unconventional activation of CD4+ T cell leading to an uncontrolled effector
      response and inflammation. The product of B cell differentiation, the
      plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells
      since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi
      infected mice.

PMID- 29209315
TI  - Gradual Increase of FcgammaRIIIa/CD16a Expression and Shift toward IFN-gamma
      Secretion during Differentiation of CD56dim Natural Killer Cells.
AB  - Natural killer (NK) cell effector functions include cytotoxicity and secretion of
      cytokines such as interferon-gamma (IFN-gamma). The immature CD56bright subset of
      human NK cells lacks expression of FcgammaRIIIa/CD16a, one of the low-affinity
      immunoglobulin G receptors, or exhibits low-density expression (CD56brightCD16
      /dim) and produces IFN-gamma in response to cytokine stimulation, whereas the
      mature CD56dimCD16+ subset is the most cytotoxic one. A further
      differentiation/maturation of the latter subset according to the gradual loss of
      NKG2A and/or gain of KIR2DL (CD158a and CD158b) has been demonstrated and the
      ability to produce IFN-gamma in response to activating receptor (AR) co
      engagement is gradually acquired during terminal differentiation. In the course
      of flow cytometry analysis of CD56dim NK cells, we noted a substantial
      intraindividual heterogeneity of expression of FcgammaRIIIa. FcgammaRIIIa is
      unique among ARs: it does not require the co-engagement of other ARs to induce
      substantial cytotoxicity or cytokine synthesis in CD56dim cells. We, therefore,
      investigated whether individual differentiation/maturation of polyclonal CD56dim
      NK cells defined by expression of NKG2A/KIR2DL is related to FcgammaRIIIa
      expression and to the heterogeneity of NK cell responses upon FcgammaRIIIa
      engagement. When we analyzed unstimulated CD56dim cells by increasing level of
      FcgammaRIIIa expression, we found that the proportion of the more differentiated
      CD158a,h+ and/or CD158b,j+ cells and that of the less differentiated NKG2A+ cells
      gradually increased and decreased, respectively. FcgammaRIIIa engagement by using
      plate-bound murine anti-CD16 monoclonal antibody (mAb) or rituximab or
      trastuzumab (two therapeutic mAbs), resulted in donor-dependent partial
      segregation of IFN-gamma-producing and/or degranulating CD56dim cells.
      Importantly, the proportion of CD158a,h/b,j+ cells and that of NKG2A+ cells was
      increased and decreased, respectively, IFN-gamma-producing cells, whereas these
      proportions were poorly modified in degranulating cells. Similar results were
      observed after engagement of ARs by a combination of mAbs targeting NKG2D, NKp30,
      NKp46, and 2B4. Thus, the gradual increase of FcgammaRIIIa expression is an
      important feature of the differentiation/maturation of CD56dim cells and this
      differentiation/maturation is associated with a shift in functionality toward IFN
      gamma secretion observed upon both FcgammaRIIIa-dependent and FcgammaRIIIa
      independent stimulation. The functional heterogeneity related to the
      differentiation/maturation of CD56dim NK cells could be involved in the
      variability of the clinical responses observed in patients treated with
      therapeutic mAbs.

PMID- 29209316
TI  - Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural
      Mesothelioma Microenvironment and Promotes Tumor Growth.
AB  - C1q is the first recognition subcomponent of the complement classical pathway,
      which acts toward the clearance of pathogens and apoptotic cells. C1q is also
      known to modulate a range of functions of immune and non-immune cells, and has
      been shown to be involved in placental development and sensorial synaptic
      pruning. We have recently shown that C1q can promote tumor by encouraging their
      adhesion, migration, and proliferation in addition to angiogenesis and
      metastasis. In this study, we have examined the role of human C1q in the
      microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer
      commonly associated with exposure to asbestos. We found that C1q was highly
      expressed in all MPM histotypes, particularly in epithelioid rather than in
      sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic
      acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion
      and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2,
      SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement
      cascade. Consistent with the modular organization of the globular domain, we
      demonstrated that C1q may bind to HA through ghA module, whereas it may interact
      with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds
      to HA and enhances the tumor growth promoting cell adhesion and proliferation.
      These data can help develop novel diagnostic markers and molecular targets for
      MPM.

PMID- 29209317
TI  - beta1-Adrenergic Receptor Contains Multiple IAk and IEk Binding Epitopes That
      Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A/J
      Mice.
AB  - Myocarditis/dilated cardiomyopathy (DCM) patients can develop autoantibodies to
      various cardiac antigens and one major antigen is beta1-adrenergic receptor
      (beta1AR). Previous reports indicate that animals immunized with a beta1AR
      fragment encompassing, 197-222 amino acids for a prolonged period can develop DCM
      by producing autoantibodies, but existence of T cell epitopes, if any, were
      unknown. Using A/J mice that are highly susceptible to lymphocytic myocarditis,
      we have identified beta1AR 171-190, beta1AR 181-200, and beta1AR 211-230 as the
      major T cell epitopes that bind major histocompatibility complex class II/IAk or
      IEk alleles, and by creating IAk and IEk dextramers, we demonstrate that the CD4
      T cell responses to be antigen-specific. Of note, all the three epitopes were
      found also to stimulate CD8 T cells suggesting that they can act as common
      epitopes for both CD4 and CD8 T cells. While, all epitopes induced only mild
      myocarditis, the disease-incidence was enhanced in animals immunized with all the
      three peptides together as a cocktail. Although, antigen-sensitized T cells
      produced mainly interleukin-17A, their transfer into naive animals yielded no
      disease. But, steering for T helper 1 response led the T cells reacting to one
      epitope, beta1AR 181-200 to induce severe myocarditis in naive mice. Finally, we
      demonstrate that all three beta1AR epitopes to be unique for T cells as none of
      them induced antibody responses. Conversely, animals immunized with a non-T cell
      activator, beta1AR 201-220, an equivalent of beta1AR 197-222, had antibodies
      comprising of all IgG isotypes and IgM except, IgA and IgE. Thus, identification
      of T cell and B cell epitopes of beta1AR may be helpful to determine beta1AR
      reactive autoimmune responses in various experimental settings in A/J mice.

PMID- 29209318
TI  - The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the
      NLRP3 Inflammasome.
AB  - Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one
      of the most prevalent subcutaneous mycosis in tropical and subtropical countries.
      CBM is a poorly characterized chronic infection that commonly starts after
      transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi.
      Recently, we have shown that unlike conidia, hyphae and muriform cells (the
      parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response
      pattern in vivo, which comprises the production of an inflammasome-derived
      cytokine, IL-1beta. Nonetheless, the mechanisms underlying IL-1beta production
      and maturation upon F. pedrosoi infection and its functional output in the course
      of CBM remains unknown. We show here that F. pedrosoi hyphae, differently from
      conidia, induce IL-1beta secretion in both bone marrow-derived dendritic cells
      and macrophages. Using inhibitors and knockout cells, we demonstrated that the
      mechanisms underlying IL-1beta production by hyphae-infected macrophages were
      dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway.
      Furthermore, F. pedrosoi promoted a NLRP3-dependent inflammasome activation,
      which required potassium efflux, reactive oxygen species production,
      phagolysosomal acidification, and cathepsin B release as triggers. IL-1beta
      processing and release was mediated primarily by caspase-1 and, to a lesser
      extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM
      model that F. pedrosoi elicits a NLRP3-regulated IL-1beta and interleukin-18
      release in vivo, but without NLRP3 inflammasome activation interfering in the
      course of the experimental infection.

PMID- 29209319
TI  - Mesenchymal Stem Cells Induce Expression of CD73 in Human Monocytes In Vitro and
      in a Swine Model of Myocardial Infarction In Vivo.
AB  - The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the
      hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado),
      respectively. This shifts the pro-inflammatory milieu induced by extracellular
      ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs)
      have potent immunomodulatory capabilities, including monocyte modulation toward
      an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that
      human cardiac adipose tissue-derived MSCs (cATMSCs) and umbilical cord MSCs
      similarly polarize monocytes toward a regulatory M2 phenotype, which maintained
      the expression of CD39 and induced expression of CD73 in a cell contact dependent
      fashion, correlating with increased functional activity. In addition, the local
      treatment with porcine cATMSCs using an engineered bioactive graft promoted the
      in vivo CD73 expression on host monocytes in a swine model of myocardial
      infarction. Our results suggest the upregulation of ectonucleotidases on MSC
      conditioned monocytes as an effective mechanism to amplify the long-lasting
      immunomodulatory and healing effects of MSCs delivery.

PMID- 29209320
TI  - How Mucosal Epithelia Deal with Stress: Role of NKG2D/NKG2D Ligands during
      Inflammation.
AB  - Mucosal epithelia encounter both physicochemical and biological stress during
      their life and have evolved several mechanisms to deal with them, including
      regulation of immune cell functions. Stressed and damaged cells need to be
      cleared to control local inflammation and trigger tissue healing. Engagement of
      the activating NKG2D receptor is one of the most direct mechanisms involved in
      the recognition of stressed cells by the immune system. Indeed, injured cells
      promptly express NKG2D ligands that in turn mediate the activation of lymphocytes
      of both innate and adaptive arms of the immune system. This review focuses on
      different conditions that are able to modulate NKG2D ligand expression on the
      epithelia. Special attention is given to the mechanisms of immunosurveillance
      mediated by natural killer cells, which are finely tuned by NKG2D. Different
      types of stress, including viral and bacterial infections, chronic inflammation,
      and cigarette smoke exposure, are discussed as paradigmatic conditions for NKG2D
      ligand modulation, and the implications for tissue homeostasis are discussed.

PMID- 29209321
TI  - Consumption of Diet Containing Free Amino Acids Exacerbates Colitis in Mice.
AB  - Dietary proteins can influence the maturation of the immune system, particularly
      the gut-associated lymphoid tissue, when consumed from weaning to adulthood.
      Moreover, replacement of dietary proteins by amino acids at weaning has been
      shown to impair the generation of regulatory T cells in the gut as well as immune
      activities such as protective response to infection, induction of oral and nasal
      tolerance as well as allergic responses. Polymeric and elemental diets are used
      in the clinical practice, but the specific role of intact proteins and free amino
      acids during the intestinal inflammation are not known. It is plausible that
      these two dietary nitrogen sources would yield distinct immunological outcomes
      since proteins are recognized by the immune system as antigens and amino acids do
      not bind to antigen-recognition receptors but instead to intracellular receptors
      such as mammalian target of rapamycin (mTOR). In this study, our aim was to
      evaluate the effects of consumption of an amino acid-containing diet (AA diet)
      versus a control protein-containing diet in adult mice at steady state and during
      colitis development. We showed that consumption of a AA diet by adult mature mice
      lead to various immunological changes including decrease in the production of
      serum IgG as well as increase in the levels of IL-6, IL-17A, TGF-beta, and IL-10
      in the small and large intestines. It also led to changes in the intestinal
      morphology, to increase in intestinal permeability, in the number of total and
      activated CD4+ T cells in the small intestine as well as in the frequency of
      proliferating cells in the colon. Moreover, consumption of AA diet during and
      prior to development of dextran sodium sulfate-induced colitis exacerbated gut
      inflammation. Administration of rapamycin during AA diet consumption prevented
      colitis exacerbation suggesting that mTOR activation was involved in the effects
      triggered by the AA diet. Therefore, our study suggests that different outcomes
      can result from the use of diets containing either intact proteins or free amino
      acids such as elemental, semielemental, and polymeric diets during intestinal
      inflammation. These results may contribute to the design of nutritional
      therapeutic intervention for inflammatory bowel diseases.

PMID- 29209322
TI  - Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook.
AB  - Tremendous effort has been expended over the past two and a half decades to
      understand many aspects of camelid heavy chain antibodies, from their biology,
      evolution, and immunogenetics to their potential applications in various fields
      of research and medicine. In this article, I present a historical perspective on
      the development of camelid single-domain antibodies (sdAbs or VHHs, also widely
      known as nanobodies) since their discovery and discuss the advantages and
      disadvantages of these unique molecules in various areas of research, industry,
      and medicine. Commercialization of camelid sdAbs exploded in 2001 with a flurry
      of patents issued to the Vrije Universiteit Brussel (VUB) and later taken on by
      the Vlaams Interuniversitair Instituut voor Biotechnologie (VIB) and, after 2002,
      the VIB-founded spin-off company, Ablynx. While entrepreneurial spirit has
      certainly catalyzed the exploration of nanobodies as marketable products, IP
      restrictions may be partially responsible for the relatively long time span
      between the discovery of these biomolecules and their entry into the
      pharmaceutical market. It is now anticipated that the first VHH-based antibody
      drug, Caplacizumab, a bivalent anti-vWF antibody for treating rare blood clotting
      disorders, may be approved and commercialized in 2018 or shortly thereafter. This
      elusive first approval, along with the expiry of key patents, may substantially
      alter the scientific and biomedical landscape surrounding camelid sdAbs and pave
      the way for their emergence as mainstream biotherapeutics.

PMID- 29209324
TI  - Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8+ T Cell
      Responses According to Human Leukocyte Antigen Class I Allotypes and
      Intraindividual Dominance.
AB  - To define whether individual human leukocyte antigen (HLA) class I allotypes are
      used preferentially in human cytomegalovirus (CMV)-specific cytotoxic T
      lymphocyte responses, CD8+ T cell responses restricted by up to six HLA class I
      allotypes in an individual were measured in parallel using K562-based artificial
      antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class
      I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C) present in 50 healthy Korean
      donors. The CD8+ T cell responses to pp65 in the HLA-C allotypes were lower than
      responses to those in HLA-A and -B allotypes and there was no difference between
      the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest
      magnitude and frequency of immune responses to pp65 at each HLA class I locus.
      However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did
      not show any immune responses. Although each individual has up to six different
      HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes,
      and 2% showed three allotypes that responded to pp65. Interestingly, the
      frequencies of HLA-A alleles were significantly correlated with the positivity of
      specific allotypes. Our results demonstrate that specific HLA class I allotypes
      are preferentially used in the CD8+ T cell immune response to pp65 and that a
      hierarchy among HLA class I allotypes is present in an individual.

PMID- 29209323
TI  - Non-Neutralizing Antibodies Directed against HIV and Their Functions.
AB  - B cells produce a plethora of anti-HIV antibodies (Abs) but only few of them
      exhibit neutralizing activity. This was long considered a profound limitation for
      the enforcement of humoral immune responses against HIV-1 infection, especially
      since these neutralizing Abs (nAbs) are extremely difficult to induce. However,
      increasing evidence shows that additional non-neutralizing Abs play a significant
      role in decreasing the viral load, leading to partial and sometimes even total
      protection. Mechanisms suspected to participate in protection are numerous. They
      involve the Fc domain of Abs as well as their Fab part, and consequently the
      induced Ab isotype will be determinant for their functions, as well as the
      quantity and quality of the Fc-receptors (FcRs) expressed on immune cells. Fc
      mediated inhibitory functions, such as Ab-dependent cellular cytotoxicity,
      antibody-dependent cellular phagocytosis, aggregation, and even immune activation
      have been proposed. However, as for nAbs, the non-neutralizing activities are
      limited to a subset of anti-HIV Abs. An improved in-depth characterization of the
      Abs displaying these functional responses is required for the development of new
      vaccination strategies, which aim to selectively trigger the B cells able to
      induce the right functional Ab combinations both at the right place and at the
      right time. This review summarizes our current knowledge on non-neutralizing
      functional inhibitory Abs and discusses the potential benefit of inducing them
      via vaccination. We also provide new insight into the roles of the FcgammaR
      mediated Ab therapeutics in clinical trials for HIV diseases.

PMID- 29209325
TI  - Probiotic Enhanced Intestinal Immunity in Broilers against Subclinical Necrotic
      Enteritis.
AB  - Along with banning of antibiotics, necrotic enteritis (NE), especially
      subclinical NE (SNE) whereby no clinical signs are present in chicks, has become
      one of the most threatening problems in poultry industry. Therefore, increasing
      attention has been focused on research and application of effective probiotic
      strains, as an alternative to antibiotics, to prevent SNE in broilers. In the
      present study, we evaluated the effects of Lactobacillus johnsonii BS15 on the
      prevention of SNE in broilers. Specifically, assessment determined the growth
      performance and indexes related to intestinal mucosal immunity in the ileum and
      cecal tonsil of broilers. A total of 300 1-day-old Cobb 500 chicks were randomly
      distributed into the following 5 groups: control group (fed with basal diet + de
      Man, Rogosa, and Sharpe liquid medium [normal diet]), SNE group (normal diet),
      BS15 group (basal diet + 1 * 106 colony-forming units BS15/g as fed [BS15 diet]),
      treatment group (normal diet [days 1-28] + BS15 diet [days 29-42]), and
      prevention group (BS15 diet [days 1-28] + normal diet [days 29-42]) throughout a
      42-day experimental period. SNE infection was treated for all chicks in the SNE,
      BS15, treatment, and prevention groups. The present results demonstrated that
      BS15 supplementation of feeds in BS15 and prevention groups exerted a positive
      effect on preventing negative influences on growth performance; these negative
      influences included low body weight gain and increased feed conversion ratio
      caused by SNE. Although no changes were detected in all determined indexes in
      cecal tonsils, BS15-treated broilers were free from SNE-caused damage in villi in
      the ileum. BS15 inhibited SNE-caused decrease in immunoglobulins in the ileum. In
      the lamina propria of ileum, T cell subsets of lymphocytes influenced by SNE were
      also controlled by BS15. BS15 affected antioxidant abilities of the ileum and
      controlled SNE-induced mitochondrion-mediated apoptosis by positively changing
      contents and/or mRNA expression levels of apoptosis-related proteins. These
      findings indicate that BS15 supplementation may prevent SNE-affected growth
      decline mainly through enhancing intestinal immunity in broilers.

PMID- 29209326
TI  - Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 "Knockouts" Tell
      Us About Pathogenesis.
AB  - Myeloid cells initiate immune responses and are crucial to control infections. In
      the case of retroviruses, however, myeloid cells also promote pathogenesis by
      enabling viral dissemination; a process extensively studied in vitro using human
      immunodeficiency virus type 1 (HIV-1). This viral hijacking mechanism does not
      rely on productive myeloid cell infection but requires HIV-1 capture via Siglec
      1/CD169, a receptor expressed on myeloid cells that facilitates the infection of
      bystander target cells. Murine retroviruses are also recognized by Siglec-1, and
      this interaction is required for robust retroviral infection in vivo. Yet, the
      relative contribution of Siglec-1-mediated viral dissemination to HIV-1 disease
      progression remains unclear. The identification of human null individuals lacking
      working copies of a particular gene enables studying how this loss affects
      disease progression. Moreover, it can reveal novel antiviral targets whose
      blockade might be therapeutically effective and safe, since finding null
      individuals in natura uncovers dispensable functions. We previously described a
      loss-of-function variant in SIGLEC-1. Analysis of a large cohort of HIV-1
      infected individuals identified homozygous and heterozygous subjects, whose cells
      were functionally null or partially defective for Siglec-1 activity in HIV-1
      capture and transmission ex vivo. Nonetheless, analysis of the effect of Siglec-1
      truncation on progression to AIDS was not conclusive due to the limited cohort
      size, the lack of complete clinical records, and the restriction to study only
      off-therapy periods. Here, we review how the study of loss-of-function variants
      might serve to illuminate the role of myeloid cells in viral pathogenesis in vivo
      and the challenges ahead.

PMID- 29209328
TI  - Antibodies against MYC-Associated Zinc Finger Protein: An Independent Marker in
      Acute Coronary Syndrome?
AB  - Introduction: Atherosclerosis is considered the pathophysiology underlying
      cardiovascular (CVD), cerebrovascular, and peripheral vascular diseases. Evidence
      supporting an autoimmune component is emerging, with imaging studies correlating
      MYC-associated zinc finger protein antibody (MAZ-Ab) optical density (OD) with
      plaque activity. This study compares MAZ-Ab OD on ELISA testing among patients
      presenting with acute coronary syndromes (ACSs) to healthy controls and
      investigates the association of MAZ-Ab to traditional CVD risk factors. Methods:
      Patients admitted with ACSs between August 2007 and July 2011 were included.
      Serum samples taken at presentation were retrospectively tested for MAZ-Ab and
      compared with serum from healthy volunteers with no CVD risk factors. Large-scale
      assessment of post-ACS prognostic relevance was performed using the established
      PLATO cohort. Results: In total 174 ACS patients and 96 controls were included.
      Among ACS patients, median MAZ-Ab OD was higher compared with controls (0.46 vs.
      0.27; p = 0.001). Although the majority of ACS patients (116/174; 67%) had
      suffered from a ST-elevation myocardial infarction, no significant differences in
      MAZ-Ab titers were evident between ACS subtypes (p = 0.682). No associations
      between MAZ-Ab OD and conventional CVD risk factors were identified. Large-scale
      testing revealed no prognostic stratification regarding reinfarction (OR 1.04
      [95% CI: 0.94-1.16]; p = 0.436). Conclusion: MAZ-Ab OD was higher or all ACS
      phenotypes compared with controls. Given current understanding of MAZ-Ab
      function, these findings support an autoimmune component to CVD independent of
      conventional risk factors and indeed the extent of end-organ damage.

PMID- 29209329
TI  - Angiotensin-(1-7) Promotes Resolution of Neutrophilic Inflammation in a Model of
      Antigen-Induced Arthritis in Mice.
AB  - Defective resolution of inflammation may be crucial for the initiation and
      development of chronic inflammatory diseases, such as arthritis. Therefore, it
      has been suggested that therapeutic strategies based on molecules that facilitate
      inflammation resolution present great potential for the treatment of chronic
      inflammatory diseases. In this study, we investigated the effects and role of
      angiotensin-(1-7) [Ang-(1-7)] in driving resolution of neutrophilic inflammation
      in a model of arthritis. For this purpose, male C57BL/6 mice were subjected to
      antigen-induced arthritis and treated with Ang-(1-7) at the peak of the
      inflammatory process. Analysis of the number of inflammatory cells, apoptosis,
      and immunofluorescence for NF-kappaB was performed in the exudate collected from
      the knee cavity. Neutrophil accumulation in periarticular tissue was measured by
      assaying myeloperoxidase activity. Apoptosis of human neutrophil after treatment
      with Ang-(1-7) was evaluated morphologically and by flow cytometry, and NF-kappaB
      phosphorylation by immunofluorescence. Efferocytosis was evaluated in vivo.
      Therapeutic treatment with Ang-(1-7) at the peak of inflammation promoted
      resolution, an effect associated with caspase-dependent neutrophils apoptosis and
      NF-kappaB inhibition. Importantly, Ang-(1-7) was also able to induce apoptosis of
      human neutrophils, an effect associated with NF-kappaB inhibition. The pro
      resolving effects of Ang-(1-7) were inhibited by the Mas receptor antagonist
      A779. Finally, we showed that Ang-(1-7) increased the efferocytic ability of
      murine macrophages. Our results clearly demonstrate that Ang-(1-7) resolves
      neutrophilic inflammation in vivo acting in two key step of resolution: apoptosis
      of neutrophils and their removal by efferocytosis. Ang-(1-7) is a novel mediator
      of resolution of inflammation.

PMID- 29209327
TI  - Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for
      Melanoma.
AB  - Melanoma is a highly aggressive form of skin cancer that frequently metastasizes
      to vital organs, where it is often difficult to treat with traditional therapies
      such as surgery and radiation. In such cases of metastatic disease, immunotherapy
      has emerged in recent years as an exciting treatment option for melanoma
      patients. Despite unprecedented successes with immune therapy in the clinic, many
      patients still experience disease relapse, and others fail to respond at all,
      thus highlighting the need to better understand factors that influence the
      efficacy of antitumor immune responses. At the heart of antitumor immunity are
      dendritic cells (DCs), an innate population of cells that function as critical
      regulators of immune tolerance and activation. As such, DCs have the potential to
      serve as important targets and delivery agents of cancer immunotherapies. Even
      immunotherapies that do not directly target or employ DCs, such as checkpoint
      blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs
      that shape the quality of therapy-associated antitumor immunity. Therefore,
      understanding factors that regulate the function of tumor-associated DCs is
      critical for optimizing both current and future immunotherapeutic strategies for
      treating melanoma. To this end, this review focuses on advances in our
      understanding of DC function in the context of melanoma, with particular emphasis
      on (1) the role of immunogenic cell death in eliciting tumor-associated DC
      activation, (2) immunosuppression of DC function by melanoma-associated factors
      in the tumor microenvironment, (3) metabolic constraints on the activation of
      tumor-associated DCs, and (4) the role of the microbiome in shaping the
      immunogenicity of DCs and the overall quality of anti-melanoma immune responses
      they mediate. Additionally, this review highlights novel DC-based immunotherapies
      for melanoma that are emerging from recent progress in each of these areas of
      investigation, and it discusses current issues and questions that will need to be
      addressed in future studies aimed at optimizing the function of melanoma
      associated DCs and the antitumor immune responses they direct against this
      cancer.

PMID- 29209330
TI  - The Enigma of Heat Shock Proteins in Immune Tolerance.
AB  - The fundamental problem of autoimmune diseases is the failure of the immune
      system to downregulate its own potentially dangerous cells, which leads to
      destruction of tissue expressing the relevant autoantigens. Current
      immunosuppressive therapies offer relief but fail to restore the basic condition
      of self-tolerance. They do not induce long-term physiological regulation
      resulting in medication-free disease remissions. Heat shock proteins (HSPs) have
      shown to possess the capacity of inducing lasting protective immune responses in
      models of experimental autoimmune diseases. Especially mycobacterial HSP60 and
      HSP70 were shown to induce disease inhibitory IL-10-producing regulatory T cells
      in many different models. This in itself may seem enigmatic, since based on
      earlier studies, HSPs were also coined sometimes as pro-inflammatory damage
      associated molecular patterns. First clinical trials with HSPs in rheumatoid
      arthritis and type I diabetes have also indicated their potential to restore
      tolerance in autoimmune diseases. Data obtained from the models have suggested
      three aspects of HSP as being critical for this tolerance promoting potential: 1.
      evolutionary conservation, 2. most frequent cytosolic/nuclear MHC class II
      natural ligand source, and 3. upregulation under (inflammatory) stress. The
      combination of these three aspects, which are each relatively unique for HSP, may
      provide an explanation for the enigmatic immune tolerance promoting potential of
      HSP.

PMID- 29209331
TI  - Sialic Acids in the Immune Response during Sepsis.
AB  - Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a group of cell
      surface transmembrane receptors expressed on immune cells, and regulate immune
      balance in inflammatory diseases. Sepsis is a life-threatened inflammatory
      syndrome induced by infection, and the pathogenesis of sepsis includes immune
      dysregulation, inflammation, and coagulation disorder. Here, we reviewed the
      various roles acted by Siglecs family in the pathogenesis of sepsis. Siglec-1,
      Siglec-5, and Siglec-14 play bidirectional roles through modulation of
      inflammation and immunity. Siglec-2 regulates the immune balance during infection
      by modulating B cell and T cell response. Siglec-9 helps endocytosis of toll-like
      receptor 4, regulates macrophages polarization, and inhibits the function of
      neutrophils during infection. Siglec-10 inhibits danger-associated molecular
      patterns induced inflammation, helps the initiation of antigen response by T
      cells, and decreases B-1a cell population to weaken inflammation. Regulating the
      Siglecs function in the different stages of sepsis holds great potential in the
      therapy of sepsis.

PMID- 29209332
TI  - Complement Receptor 3 Has Negative Impact on Tumor Surveillance through
      Suppression of Natural Killer Cell Function.
AB  - Complement receptor 3 (CR3) is expressed abundantly on natural killer (NK) cells;
      however, whether it plays roles in NK cell-dependent tumor surveillance is
      largely unknown. Here, we show that CR3 is an important negative regulator of NK
      cell function, which has negative impact on tumor surveillance. Mice deficient in
      CR3 (CD11b-/- mice) exhibited a more activated NK phenotype and had enhanced NK
      dependent tumor killing. In a B16-luc melanoma-induced lung tumor growth and
      metastasis model, mice deficient in CR3 had reduced tumor growth and metastases,
      compared with WT mice. In addition, adaptive transfer of NK cells lacking CR3
      (into NK-deficient mice) mediated more efficient suppression of tumor growth and
      metastases, compared with the transfer of CR3 sufficient NK cells, suggesting
      that CR3 can impair tumor surveillance through suppression of NK cell function.
      In vitro analyses showed that engagement of CR3 with iC3b (classical CR3 ligand)
      on NK cells negatively regulated NK cell activity and effector functions (i.e.
      direct tumor cell killing, antibody-dependent NK-mediated tumor killing). Cell
      signaling analyses showed that iC3b stimulation caused activation of Src homology
      2 domain-containing inositol-5-phosphatase-1 (SHIP-1) and JNK, and suppression of
      ERK in NK cells, supporting that iC3b mediates negative regulation of NK cell
      function through its effects on SHIP-1, JNK, and ERK signal transduction
      pathways. Thus, our findings demonstrate a previously unknown role for CR3 in
      dysregulation of NK-dependent tumor surveillance and suggest that the iC3b/CR3
      signaling is a critical negative regulator of NK cell function and may represent
      a new target for preserving NK cell function in cancer patients and improving NK
      cell-based therapy.

PMID- 29209333
TI  - Inhibition of Acute Graft-versus-Host Disease with Retention of Graft-versus
      Tumor Effects by Dimethyl Fumarate.
AB  - Acute graft-versus-host disease (aGVHD) remains a clinical challenge and a major
      source of morbidity and mortality following allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). Dimethyl fumarate (DMF), an activator of Nrf2, has
      been shown to have anti-inflammatory and immunomodulatory properties without
      significant immunosuppression. We therefore hypothesized that DMF could be
      potentially harnessed for the treatment of aGVHD with retention of graft-versus
      tumor effect. In this study, we showed that DMF significantly inhibited
      alloreactive T cell responses in vitro in mixed lymphocyte reaction assay.
      Administration of DMF significantly alleviated the severity, histological damage,
      and the overall mortality of aGVHD in an MHC-mismatched aGVHD model. DMF
      administration reduced the activation and effector function of donor T cells in
      vitro and in vivo. In addition, DMF treatment upregulated antioxidant enzymes
      heme oxygenase-1 and glutathione S-transferase-alpha1 expressions. Furthermore,
      DMF treatment markedly increased the frequencies of Treg cells. Depletion of
      CD25+ cells in DMF recipients aggravated aGVHD mortality compared with IgG
      control recipients. DMF could promote Treg cell differentiation in a dose
      dependent manner by upregulating TGF-beta expression in vitro. Most importantly,
      DMF administration preserved graft-versus-leukemia effect after bone marrow
      transplantation. In conclusion, our findings demonstrated DMF as a promising
      agent for the prevention of aGVHD after allo-HSCT.

PMID- 29209334
TI  - Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute
      Inflammatory Responses In Vivo.
AB  - Chemerin is a chemotactic protein that induces migration of several immune cells
      including macrophages, immature dendritic cells, and NK cells. Chemerin binds to
      three G protein-coupled receptors (GPCRs), including CCRL2. The exact function of
      CCRL2 remains unclear. CCRL2 expression is rapidly upregulated during
      inflammation, but it lacks the intracellular DRYLAIV motif required for classical
      GPCR downstream signalling pathways, and it has not been reported to internalise
      chemerin upon binding. The aim of this study was to investigate what role if any
      CCRL2 plays during acute inflammation. Using the zymosan- and thioglycollate
      induced murine models of acute inflammation, we report that mice deficient in the
      Ccrl2 gene display exaggerated local and systemic inflammatory responses,
      characterised by increased myeloid cell recruitment. This amplified myeloid cell
      recruitment was associated with increased chemerin and CXCL1 levels. Furthermore,
      we report that the inflammatory phenotype observed in these mice is dependent
      upon elevated levels of endogenous chemerin. Antibody neutralisation of chemerin
      activity in Ccrl2-/- mice abrogated the amplified inflammatory responses.
      Importantly, chemerin did not directly recruit myeloid cells but rather increased
      the production of other chemotactic proteins such as CXCL1. Administration of
      recombinant chemerin to wild-type mice before inflammatory challenge
      recapitulated the increased myeloid cell recruitment and inflammatory mediator
      production observed in Ccrl2-/- mice. We have demonstrated that the absence of
      CCRL2 results in increased levels of local and systemic chemerin levels and
      exacerbated inflammatory responses during acute inflammatory challenge. These
      results further highlight the importance of chemerin as a therapeutic target in
      inflammatory diseases.

PMID- 29209335
TI  - Identification and Expression Profile of CYPome in Perennial Ryegrass and Tall
      Fescue in Response to Temperature Stress.
AB  - Plant cytochrome P450s are involved in a wide range of biosynthetic reactions
      that generate various biomolecules, including a variety of defensive compounds.
      Perennial ryegrass (Lolium perenne) and tall fescue (Festuca arundinacea) are two
      major species of turf and forage grasses that usually experience low temperature
      below -10 degrees C and high temperature over 38 degrees C around the world. In
      this study, we re-analyzed transcriptome of perennial ryegrass and tall fescue
      treated with heat and cold stress. Thus, we can evaluate P450 composition in
      these species and confirm whether P450 genes response to temperature stress. We
      identified 277 and 319 P450 transcripts with open reading frames larger than 300
      bp, respectively. These P450 transcripts were mainly classed in the CYP71, 51,
      94, 89, 72, and 734 families. In perennial ryegrass and tall fescue, a total of
      66 and 62 P450 transcripts were up-regulated, and 65 and 117 transcripts were
      down-regulated when subjected to heat stress, respectively. When exposed to cold
      stress, 60 and 73 transcripts were up-regulated, and 59 and 77 transcripts were
      down-regulated in perennial ryegrass and tall fescue. Among these differentially
      expressed transcripts, 64 and 87 of them showed expression level changes that
      followed the same trend, and these temperature-responsive genes primarily belong
      to the CYP71, 72 and 99 families. Besides, heat and cold stress altered
      phenylalanine and brassinosteroid involved P450 transcripts in perennial ryegrass
      and tall fescue. P450 transcripts involved in the metabolism of these compounds
      showed a strong response to heat and/or cold stress, indicating that they likely
      play important roles in temperature acclimation in these two species. The CYPome
      provide a genetic base for the future functional studies, as well as genetic
      studies that may improve stress tolerance for perennial ryegrass and tall fescue
      to extreme temperature.

PMID- 29209336
TI  - DRDB: An Online Date Palm Genomic Resource Database.
AB  - Background: Date palm (Phoenix dactylifera L.) is a cultivated woody plant with
      agricultural and economic importance in many countries around the world. With the
      advantages of next generation sequencing technologies, genome sequences for many
      date palm cultivars have been released recently. Short sequence repeat (SSR) and
      single nucleotide polymorphism (SNP) can be identified from these genomic data,
      and have been proven to be very useful biomarkers in plant genome analysis and
      breeding. Results: Here, we first improved the date palm genome assembly using
      130X of HiSeq data generated in our lab. Then 246,445 SSRs (214,901 SSRs and
      31,544 compound SSRs) were annotated in this genome assembly; among the SSRs,
      mononucleotide SSRs (58.92%) were the most abundant, followed by di- (29.92%),
      tri- (8.14%), tetra- (2.47%), penta- (0.36%), and hexa-nucleotide SSRs (0.19%).
      The high-quality PCR primer pairs were designed for most (174,497; 70.81% out of
      total) SSRs. We also annotated 6,375,806 SNPs with raw read depth>=3 in 90%
      cultivars. To further reduce false positive SNPs, we only kept 5,572,650 (87.40%
      out of total) SNPs with at least 20% cultivars support for downstream analyses.
      The high-quality PCR primer pairs were also obtained for 4,177,778 (65.53%) SNPs.
      We reconstructed the phylogenetic relationships among the 62 cultivars using
      these variants and found that they can be divided into three clusters, namely
      North Africa, Egypt - Sudan, and Middle East - South Asian, with Egypt - Sudan
      being the admixture of North Africa and Middle East - South Asian cultivars; we
      further confirmed these clusters using principal component analysis. Moreover,
      34,346 SSRs and 4,177,778 SNPs with PCR primers were assigned to shared cultivars
      for cultivar classification and diversity analysis. All these SSRs, SNPs and
      their classification are available in our database, and can be used for cultivar
      identification, comparison, and molecular breeding. Conclusion:DRDB is a
      comprehensive genomic resource database of date palm. It can serve as a
      bioinformatics platform for date palm genomics, genetics, and molecular breeding.
      DRDB is freely available at http://drdb.big.ac.cn/home.

PMID- 29209338
TI  - Can Aquatic Plants Keep Pace with Climate Change?
AB  - The persistence of species may depend upon their capacity to keep pace with
      climate change. However, dispersal has been ignored in the vast majority of
      studies that aimed at estimating and predicting range shifts as a response to
      climate change. Long distance dispersal (LDD) in particular might promote rapid
      range shifts and allow species to track suitable habitat. Many aquatic plant
      species are dispersed by birds and have the potential to be dispersed over
      hundreds of kilometers during the bird migration seasons. I argue that such
      dispersal potential might be critical to allow species to track climate change
      happening at unprecedented high rates. As a case study, I used dispersal data
      from three aquatic plant species dispersed by migratory birds to model range
      shifts in response to climate change projections. By comparing four dispersal
      scenarios - (1) no dispersal, (2) unlimited dispersal, (3) LDD < 100 km, and (4)
      LDD mediated by bird migratory movements -, it was shown that, for bird-mediated
      dispersal, the rate of colonization is sufficient to counterbalance the rate of
      habitat loss. The estimated rates of colonization (3.2-31.5 km?year-1) are higher
      than, for example, the rate of global warming (previously estimated at 0.42
      km?year-1). Although further studies are needed, the results suggest that these
      aquatic plant species can adjust their ranges under a severe climate change
      scenario. Therefore, investigating the dispersal capacity of species, namely
      their LDD potential, may contribute to estimate the likelihood of species to keep
      pace with climate change.

PMID- 29209337
TI  - A Plant-Feeding Nematode Indirectly Increases the Fitness of an Aphid.
AB  - Plants suffer multiple, simultaneous assaults from above and below ground. In the
      laboratory, pests and/or pathogen attack are commonly studied on an individual
      basis. The molecular response of the plant to attack from multiple organisms and
      the interaction of different defense pathways is unclear. The inducible systemic
      responses of the potato (Solanum tuberosum L.) host plant were analyzed to
      characterize the plant-mediated indirect interactions between a sedentary,
      endoparasitic nematode (Globodera pallida), and a phloem-sucking herbivore (Myzus
      persicae). The reproductive success of M. persicae was greater on potato plants
      pre-infected with G. pallida compared to control plants. Salicylic acid (SA)
      increased systemically in the leaves of potato plants following nematode and
      aphid infection singly with a corresponding increase in expression of SA-mediated
      marker genes. An increase in jasmonic acid associated with aphid infection was
      suppressed when plants were co-infected with nematodes. Our data suggests a
      positive, asymmetric interaction between a sedentary endoparasitic nematode and a
      sap-sucking insect. The systemic response of the potato plant following infection
      with G. pallida indirectly influences the performance of M. persicae. This work
      reveals additional secondary benefits of controlling individual crop pests.

PMID- 29209339
TI  - Overexpression of SoCYP85A1, a Spinach Cytochrome p450 Gene in Transgenic Tobacco
      Enhances Root Development and Drought Stress Tolerance.
AB  - Brassinosteroids (BRs) play an essential role in plant growth, development, and
      responses to diverse abiotic stresses. However, previous studies mainly analyzed
      how exogenous BRs influenced plant physiological reactions to drought stress,
      therefore, genetic evidences for the endogenous BRs-mediated regulation of plant
      responses still remain elusive. In this study, a key BRs biosynthetic gene,
      SoCYP85A1 was cloned from Spinacia oleracea, which has a complete open reading
      frame of 1,392 bp encoding a 464 amino acid peptide and shares high sequence
      similarities with CYP85A1 from other plants. The expression of SoCYP85A1 which
      was higher in leaf compared with root and stem, was induced by treatments of
      PEG6000, abscisic acid (ABA), low temperature and high salt. Increases in both
      SoCYP85A1 transcripts and endogenous BRs in transgenic tobacco which resulted in
      longer primary root and more lateral roots enhanced drought tolerance compared
      with wild types. The transgenic tobacco accumulated much lower levels of reactive
      oxygen species and malondialdehyde (MDA) than wild types did, accompanied by
      significantly higher content of proline and notably enhanced activities of
      antioxidant enzymes. Besides, transcriptional expressions of six stress
      responsive genes were regulated to higher levels in transgenic lines under
      drought stress. Taken together, our results demonstrated that SoCYP85A1 involves
      in response to drought stress by promoting root development, scavenging ROS, and
      regulating expressions of stress-responsive genes.

PMID- 29209340
TI  - Abiotic Stress Responsive miRNA-Target Network and Related Markers (SNP, SSR) in
      Brassica juncea.
AB  - Abiotic stress is one of the major factors responsible for huge yield loss in
      crop plants. MicroRNAs play a key role in adaptive responses of plants under
      abiotic stress conditions through post-transcriptional gene regulations. In
      present study, 95 potential miRNAs were predicted in Brassica juncea using
      comparative genomics approach. It was noted that these miRNAs, target several
      transcription factors (TFs), transporter family proteins, signaling related
      genes, and protease encoding genes. Nineteen distinct miRNA-target regulatory
      networks were observed with significant involvement in regulation of
      transcription, response to stimulus, hormone and auxin mediated signaling pathway
      related gene ontology (GO) term. The sucrose-starch metabolism and pentose
      gluconate interconversion pathways were found significantly enriched for these
      target genes. Molecular markers such as Simple Sequence Repeats (SSR) and Single
      Nucleotide Polymorphism (SNPs) were identified on miRNAs (miR-SSRs and miR-SNPs)
      and their target genes in B. juncea. Notably, one of the miR-SNP (C/T) was found
      at the 5th position on mature region of miR2926. This C/T transition led to the
      distorted and unstable hairpin structure of miR2926, consequently complete loss
      of target function. Hence, findings from this study will lay a foundation for
      marker assisted breeding for abiotic stress tolerant varieties of B. juncea.

PMID- 29209341
TI  - The Challenge of Improving Soil Fertility in Yam Cropping Systems of West Africa.
AB  - Yam (Dioscorea spp.) is a tuber crop grown for food security, income generation,
      and traditional medicine. This crop has a high cultural value for some of the
      groups growing it. Most of the production comes from West Africa where the
      increased demand has been covered by enlarging cultivated surfaces while the mean
      yield remained around 10 t tuber ha-1. In West Africa, yam is traditionally
      cultivated without input as the first crop after a long-term fallow as it is
      considered to require a high soil fertility. African soils, however, are being
      more and more degraded. The aims of this review were to show the importance of
      soil fertility for yam, discuss barriers that might limit the adoption of
      integrated soil fertility management (ISFM) in yam-based systems in West Africa,
      present the concept of innovation platforms (IPs) as a tool to foster
      collaboration between actors for designing innovations in yam-based systems and
      provide recommendations for future research. This review shows that the
      development of sustainable, feasible, and acceptable soil management innovations
      for yam requires research to be conducted in interdisciplinary teams including
      natural and social sciences and in a transdisciplinary manner involving relevant
      actors from the problem definition, to the co-design of soil management
      innovations, the evaluation of research results, their communication and their
      implementation. Finally, this research should be conducted in diverse biophysical
      and socio-economic settings to develop generic rules on soil/plant relationships
      in yam as affected by soil management and on how to adjust the innovation supply
      to specific contexts.

PMID- 29209343
TI  - Vermicompost Improves Tomato Yield and Quality and the Biochemical Properties of
      Soils with Different Tomato Planting History in a Greenhouse Study.
AB  - A greenhouse pot test was conducted to study the impacts of replacing mineral
      fertilizer with organic fertilizers for one full growing period on soil
      fertility, tomato yield and quality using soils with different tomato planting
      history. Four types of fertilization regimes were compared: (1) conventional
      fertilizer with urea, (2) chicken manure compost, (3) vermicompost, and (4) no
      fertilizer. The effects on plant growth, yield and fruit quality and soil
      properties (including microbial biomass carbon and nitrogen, [Formula: see text]
      N, [Formula: see text]-N, soil water-soluble organic carbon, soil pH and
      electrical conductivity) were investigated in samples collected from the
      experimental soils at different tomato growth stages. The main results showed
      that: (1) vermicompost and chicken manure compost more effectively promoted plant
      growth, including stem diameter and plant height compared with other fertilizer
      treatments, in all three types of soil; (2) vermicompost improved fruit quality
      in each type of soil, and increased the sugar/acid ratio, and decreased nitrate
      concentration in fresh fruit compared with the CK treatment; (3) vermicompost led
      to greater improvements in fruit yield (74%), vitamin C (47%), and soluble sugar
      (71%) in soils with no tomato planting history compared with those in soils with
      long tomato planting history; and (4) vermicompost led to greater improvements in
      soil quality than chicken manure compost, including higher pH (averaged 7.37 vs.
      averaged 7.23) and lower soil electrical conductivity (averaged 204.1 vs.
      averaged 234.6 MUS/cm) at the end of experiment in each type of soil. We conclude
      that vermicompost can be recommended as a fertilizer to improve tomato fruit
      quality and yield and soil quality, particularly for soils with no tomato
      planting history.

PMID- 29209342
TI  - Physical, Functional and Genetic Interactions between the BEACH Domain Protein
      SPIRRIG and LIP5 and SKD1 and Its Role in Endosomal Trafficking to the Vacuole in
      Arabidopsis.
AB  - Beige and Chediak Higashi (BEACH) domain-containing proteins (BDCPs) are
      facilitators of membrane-dependent cellular processes in eukaryotes. Mutations in
      BDCPs cause malfunctions of endosomal compartments in various cell types.
      Recently, the molecular analysis of the BDCP homolog gene SPIRRIG (SPI) has
      revealed a molecular function in P-bodies and the regulation of RNA stability. We
      therefore aimed to analyze, whether SPI has also a role in membrane-dependent
      processes. In this study, we show that SPI physically interacts with endosomal
      sorting complex required for transport associated ATPase Suppressor of K+
      transport growth defect1 (SKD1) and its positive regulator, LYST Interacting
      Protein 5 (LIP5) and report genetic interactions between SPI and SKD1 and LIP5.
      We further show that the endosomal transport route of soluble proteins to the
      lytic vacuole is disturbed in spi lip5 double mutants but not in the single
      mutants. These vacuolar transport defects were suppressed by additional
      expression of SKD1. Our results indicate that the BEACH domain protein SPI has in
      addition to a role in P-bodies a function in endosomal transport routes.

PMID- 29209344
TI  - QTL Analysis of Transgressive Nematode Resistance in Tetraploid Cotton Reveals
      Complex Interactions in Chromosome 11 Regions.
AB  - Transgressive segregation in cotton (Gossypium spp.) provides an important
      approach to enhance resistance to the major pest root-knot nematode (RKN)
      Meloidogyne incognita. Our previous studies reported transgressive RKN resistance
      in an intraspecific Gossypium hirsutum resistant NemX * susceptible SJ-2
      recombinant inbred line (RIL) population and early generations of interspecific
      cross Gossypium barbadense (susceptible Pima S-7) * G. hirsutum (NemX). However,
      the underlying functional mechanisms for this phenomenon are not known. In this
      study, the region of RKN resistance gene rkn1 on chromosome (Chr) 11 and its
      homoeologous Chr 21 was fine mapped with G. raimondii D5 genome reference
      sequence. Transgressive resistance was found in the later generation of a new RIL
      population F2:7 (Pima S-7 * NemX) and one interspecific F2 (susceptible Pima S-7
      * susceptible SJ-2). QTL analysis revealed similar contributions to root-galling
      and egg-production resistance phenotypes associated with SSR marker CIR316 linked
      to resistance gene rkn1 in NemX on Chr 11 in all seven populations analyzed. In
      testcross NemX * F1 (Pima S-7 * SJ-2) marker allele CIR069-271 from Pima S-7
      linked to CIR316 contributed 63% of resistance to galling phenotype in the
      presence of rkn1. Similarly, in RIL population F2:8 (NemX * SJ-2), SJ-2 markers
      closely linked to CIR316 contributed up to 82% of resistance to root-galling.
      These results were confirmed in BC1F1 SJ-2 * F1 (NemX * SJ-2), F2 (NemX * SJ-2),
      and F2 (Pima S-7 * SJ-2) populations in which up to 44, 36, and 15% contribution
      in resistance to galling was found, respectively. Transgressive segregation for
      resistance was universal in all intra- and inter-specific populations, although
      stronger transgressive resistance occurred in later than in early generations in
      the intraspecific cross compared with the interspecific cross. Transgressive
      effects on progeny from susceptible parents are possibly provided in the rkn1
      resistance region of chromosome 11 by tandemly arrayed allele (TAA) or gene (TAG)
      interactions contributing to transgressive resistance. Complex TAA and TAG
      recombination and interactions in the rkn1 resistance region provide three genes
      and a model to study disease and transgressive resistance in polyploid plants,
      and novel genotypes for plant breeding.

PMID- 29209345
TI  - Differentiation of Three Centella Species in Australia as Inferred from
      Morphological Characteristics, ISSR Molecular Fingerprinting and Phytochemical
      Composition.
AB  - Centella asiatica is one of the popular herbs used for inflammatory and neural
      conditions. Its differentiation from similar species is currently lacking. The
      aims of this study were to differentiate the three closely related Centella
      species using methods based on morphological characters, genetic biodiversity,
      phytochemical compositions and antioxidant activities. According to the
      morphological characteristics, the collected samples were identified as three
      species: C. asiatica, Centella cordifolia and Centella erecta and clustered into
      three groups based on their morphometric variability. Dendogram constructed on
      the basis of the intersimple sequence repeats (ISSR) analyses were consistent
      with the morphological grouping. Centella cordifolia had the highest triterpene
      glycosides, phenolics and antioxidant capacity, followed by C. asiatica, then C.
      erecta, therefore, was genetically and chemically closer to C. asiatica, while C.
      erecta was distinctively different from them. The results confirm the occurrence
      of the closely related three species of Centella in Australia, and the
      differentiation among them can be achieved via the combination of morphometric,
      molecular and phytochemical methods. This first comparative botanical study on
      Centella species provides a foundation for further systematic study and medicinal
      development of Centella.

PMID- 29209346
TI  - Katanin: A Sword Cutting Microtubules for Cellular, Developmental, and
      Physiological Purposes.
AB  - KATANIN is a well-studied microtubule severing protein affecting microtubule
      organization and dynamic properties in higher plants. By regulating mitotic and
      cytokinetic and cortical microtubule arrays it is involved in the progression of
      cell division and cell division plane orientation. KATANIN is also involved in
      cell elongation and morphogenesis during plant growth. In this way KATANIN plays
      critical roles in diverse plant developmental processes including the development
      of pollen, embryo, seed, meristem, root, hypocotyl, cotyledon, leaf, shoot, and
      silique. KATANIN-dependent microtubule regulation seems to be under the control
      of plant hormones. This minireview provides an overview on available KATANIN
      mutants and discusses advances in our understanding of KATANIN biological roles
      in plants.

PMID- 29209347
TI  - Editorial: Epigenetic Modifications Associated with Abiotic and Biotic Stresses
      in Plants: An Implication for Understanding Plant Evolution.

PMID- 29209348
TI  - Phylogeography Study of the Siberian Apricot (Prunus sibirica L.) in Northern
      China Assessed by Chloroplast Microsatellite and DNA Makers.
AB  - There is evidence that a band of dry climate separated plants in East Asia into
      distinct northern and southern groups. However, few studies have focused on the
      arid belt in this region, especially with regard to plants. We analyzed genetic
      variation in 22 populations of Siberian apricot (Prunus sibirica L.), a temperate
      deciduous species distributed in this arid belt, using two chloroplast DNA
      (cpDNA) sequences, seven chloroplast microsatellite loci (cpSSRs), and 31 nuclear
      microsatellite loci (nSSRs), to study its phylogeography. Chloroplast data showed
      the complete fixation of two different genetic groups: the eastern and western
      groups. Genetic differentiation between the two groups was significant (FST =
      0.90925, p < 0.01). This pronounced phylogeographic break was also indicated by
      nSSR data, but there were disparities regarding individual populations. An
      asymmetric gene flow via pollen and seeds likely resulted in discordance between
      the present-day geography of nuclear and chloroplast lineages. There was a
      distinct boundary between the two large groups, which were fixed for two of the
      most ancestral chlorotypes. Two populations with the highest chloroplast genetic
      diversity were located in the Yanshan Mountains and Jinzhou, considered to be the
      glacial refugia. The split of chloroplasts between the eastern and western groups
      was estimated to have occurred ~0.1795 Ma, whereas nuclear divergence occurred
      approximately 13,260 years ago. Linear regression analysis showed that climatic
      factors (annual precipitation and annual mean temperature) had a significant
      correlation with mean ancestry value (P < 0.05) indicated that they were
      potential factors for the formation of the two groups. In addition, this boundary
      was a contact zone between two groups from different refugia.

PMID- 29209350
TI  - Specific Distribution of Phosphatidylglycerol to Photosystem Complexes in the
      Thylakoid Membrane.
AB  - The thylakoid membrane is the site of photochemical and electron transport
      reactions of oxygenic photosynthesis. The lipid composition of the thylakoid
      membrane, with two galactolipids, one sulfolipid, and one phospholipid, is highly
      conserved among oxygenic photosynthetic organisms. Besides providing a lipid
      bilayer matrix, thylakoid lipids are integrated in photosynthetic complexes
      particularly in photosystems I and II and play important roles in electron
      transport processes. Thylakoid lipids are differentially allocated to
      photosynthetic complexes and the lipid bilayer fraction, but distribution of each
      lipid in the thylakoid membrane is unclear. In this study, based on published
      crystallographic and biochemical data, we estimated the proportions of
      photosynthetic complex-associated and bilayer-associated lipids in thylakoid
      membranes of cyanobacteria and plants. The data suggest that ~30 mol% of
      phosphatidylglycerol (PG), the only major phospholipid in thylakoid membranes, is
      allocated to photosystem complexes, whereas glycolipids are mostly distributed to
      the lipid bilayer fraction and constitute the membrane lipid matrix. Because PG
      is essential for the structure and function of both photosystems, PG buried in
      these complexes might have been selectively conserved among oxygenic phototrophs.
      The specific and substantial allocation of PG to the deep sites of photosystems
      may need a unique mechanism to incorporate PG into the complexes possibly in
      coordination with the synthesis of photosynthetic proteins and pigments.

PMID- 29209349
TI  - Regulation of Fig (Ficus carica L.) Fruit Color: Metabolomic and Transcriptomic
      Analyses of the Flavonoid Biosynthetic Pathway.
AB  - Combined metabolomic and transcriptomic analyses were carried out with fig
      cultivar Green Peel and its color mutant "Purple Peel." Five and twenty-two
      metabolites were identified as having significantly different contents between
      fruit peels of the two cultivars at young and mature stages, respectively.
      Cyanidin O-malonylhexoside demonstrated a 3,992-fold increase in the mature
      purple peel, the first identification of a major cyanidin in fig fruit; cyanidin
      3-O-glucoside, cyanidin O-malonylhexoside O-hexoside and cyanidin-3,5-O
      diglucoside were upregulated 100-fold, revealing the anthocyanins underlying the
      purple mutation. Beyond the visible differences, there was very significant
      accumulation of the colorless flavonoids procyanidin B1, luteolin-3',7-di-O
      glucoside, epicatechin and quercetin-3-O-rhamnoside in the mature "Purple Peel"
      compared to "Green Peel." At the young stage, only cyanidin O-malonylhexoside,
      cyanidin O-malonylhexoside O-hexoside and esculetin were upregulated a few fold
      in the mutant. Transcriptome analysis revealed a downregulated expression trend
      of genes encoding phenylpropanoid and flavonoid biosynthetic pathway enzyme in
      the young "Purple Peel" compared to the young "Green Peel," whereas significant
      and simultaneous upregulation was revealed in almost all of the flavonoid and
      anthocyanin pathway components and relevant transcription factors in the mature
      stage mutant. The role of R2R3-MYB transcription factors in the color morph
      mutation and its possible relation to the activity of retrotransposons are
      discussed. Moreover, large-scale upregulation of small heat-shock protein genes
      was found in the mature mutant. This is the first work to reveal comprehensive
      metabolome and transcriptome network changes underlying a fig mutation in a
      single horticultural attribute, and its profound effects on fruit nutrition and
      quality.

PMID- 29209351
TI  - Perturbations in the Photosynthetic Pigment Status Result in Photooxidation
      Induced Crosstalk between Carotenoid and Porphyrin Biosynthetic Pathways.
AB  - Possible crosstalk between the carotenoid and porphyrin biosynthetic pathways
      under photooxidative conditions was investigated by using their biosynthetic
      inhibitors, norflurazon (NF) and oxyfluorfen (OF). High levels of protoporphyrin
      IX (Proto IX) accumulated in rice plants treated with OF, whereas Proto IX
      decreased in plants treated with NF. Both NF and OF treatments resulted in
      greater decreases in MgProto IX, MgProto IX methyl ester, and
      protochlorophyllide. Activities and transcript levels of most porphyrin
      biosynthetic enzymes, particularly in the Mg-porphyrin branch, were greatly down
      regulated in NF and OF plants. In contrast, the transcript levels of GSA, PPO1,
      and CHLD as well as FC2 and HO2 were up-regulated in NF-treated plants, while
      only moderate increases in FC2 and HO2 were observed in the early stage of OF
      treatment. Phytoene, antheraxanthin, and zeaxanthin showed high accumulation in
      NF-treated plants, whereas other carotenoid intermediates greatly decreased.
      Transcript levels of carotenoid biosynthetic genes, PSY1 and PDS, decreased in
      response to NF and OF, whereas plants in the later stage of NF treatment
      exhibited up-regulation of BCH and VDE as well as recovery of PDS. However,
      perturbed porphyrin biosynthesis by OF did not noticeably influence levels of
      carotenoid metabolites, regardless of the strong down-regulation of carotenoid
      biosynthetic genes. Both NF and OF plants appeared to provide enhanced protection
      against photooxidative damage, not only by scavenging of Mg-porphyrins, but also
      by up-regulating FC2, HO2, and Fe-chelatase, particularly with increased levels
      of zeaxanthin via up-regulation of BCH and VDE in NF plants. On the other hand,
      the up-regulation of GSA, PPO1, and CHLD under inhibition of carotenogenic flux
      may be derived from the necessity to recover impaired chloroplast biogenesis
      during photooxidative stress. Our study demonstrates that perturbations in
      carotenoid and porphyrin biosynthesis coordinate the expression of their
      biosynthetic genes to sustain plastid function at optimal levels by regulating
      their metabolic flux in plants under adverse stress conditions.

PMID- 29209353
TI  - Colombia a Source of Cacao Genetic Diversity As Revealed by the Population
      Structure Analysis of Germplasm Bank of Theobroma cacao L.
AB  - Beans of the species Theobroma cacao L., also known as cacao, are the raw
      material to produce chocolate. Colombian cacao has been classified as a fine
      flavor cacao that represents the 5% of cacao world's production. Colombian
      genetic resources from this species are conserved in ex situ and in-field
      germplasm banks, since T. cacao has recalcitrant seeds to desication and long
      term storage. Currently, the collection of T. cacao of the Colombian Corporation
      of Agricultural Research (CORPOICA) has approximately 700 germplasm accessions.
      We conducted a molecular analysis of Corpoica's cacao collection and a
      morphological characterization of some accessions with the goal to study its
      genetic diversity and population structure and, to select interesting accessions
      for the cacao's breeding program. Phenotypic evaluation was performed based on 18
      morphological traits and 4 biochemical traits. PCA analysis of morphological
      traits explained 60.6% of the total variation in seven components and 100% of the
      total variation of biochemical traits in four components, grouping the collection
      in 4 clusters for both variables. We explored 565 accessions from Corpoica's
      germplasm and 252 accessions from reference populations using 96 single
      nucleotide polymorphism (SNP) molecular markers. Molecular patterns of cacao
      Corpoica's collection were obtained amplifying specific alleles in a Fluidigm
      platform that used integrated circuits of fluids. Corpoica's collection showed
      highest genetic diversity [Expected Heterozygosity (HE = 0.314), Observed
      Heterozygosity (HO = 0.353)] that is reduced when reference populations were
      included in the dataset (HE = 0.294, HO = 0.261). The collection was divided into
      four clusters based on population structure analysis. Cacao accessions from
      distinct groups showed some taxonomic concordance and reflected their geographic
      origins. For instance, accessions classified as Criollo were clearly
      differentiated in one group and we identified two new Colombian genetic groups.
      Using a number of allelic variations based on 87 SNP markers and 22 different
      morphological/biochemical traits, a core collection with a total of 232
      accessions was selected as a primary genetic resource for cacao breeders.

PMID- 29209352
TI  - Melatonin Attenuates Potato Late Blight by Disrupting Cell Growth, Stress
      Tolerance, Fungicide Susceptibility and Homeostasis of Gene Expression in
      Phytophthora infestans.
AB  - Phytophthora infestans (P. infestans) is the causal agent of potato late blight,
      which caused the devastating Irish Potato Famine during 1845-1852. Until now,
      potato late blight is still the most serious threat to potato growth and has
      caused significant economic losses worldwide. Melatonin can induce plant innate
      immunity against pathogen infection, but the direct effects of melatonin on plant
      pathogens are poorly understood. In this study, we investigated the direct
      effects of melatonin on P. infestans. Exogenous melatonin significantly
      attenuated the potato late blight by inhibiting mycelial growth, changing cell
      ultrastructure, and reducing stress tolerance of P. infestans. Notably,
      synergistic anti-fungal effects of melatonin with fungicides on P. infestans
      suggest that melatonin could reduce the dose levels and enhance the efficacy of
      fungicide against potato late blight. A transcriptome analysis was carried out to
      mine downstream genes whose expression levels were affected by melatonin. The
      analysis of the transcriptome suggests that 66 differentially expressed genes
      involved in amino acid metabolic processes were significantly affected by
      melatonin. Moreover, the differentially expressed genes associated with stress
      tolerance, fungicide resistance, and virulence were also affected. These findings
      contribute to a new understanding of the direct functions of the melatonin on P.
      infestans and provide a potential ecofriendly biocontrol approach using a
      melatonin-based paradigm and application to prevent potato late blight.

PMID- 29209354
TI  - How Glucosinolates Affect Generalist Lepidopteran Larvae: Growth, Development and
      Glucosinolate Metabolism.
AB  - Multiple lepidopteran larvae feed successfully on plants containing
      glucosinolates despite the diverse array of toxic and deterrent breakdown
      products, such as isothiocyanates (ITCs), formed upon plant damage. While much is
      known about how specialist lepidopterans metabolize and tolerate glucosinolates,
      there is little information about the metabolic fate of these plant defense
      compounds in specialized herbivores. Employing 13C- and 14C-labeled 4
      methylsulfinylbutyl glucosinolate (glucoraphanin), we identified and quantified
      the major detoxification products of glucosinolates and ITCs in selected
      specialized and generalist larvae. While specialists prevented glucosinolate
      hydrolysis or diverted hydrolysis to form nitriles, hydrolysis in generalists
      proceeded to toxic ITCs, of which a portion were conjugated to glutathione.
      However, a large amount of ITCs remained unmodified, which may have led to the
      observed negative effects on growth and development. The performance of two
      generalist-feeding caterpillars, Spodoptera littoralis (African cotton leafworm)
      and Mamestra brassicae (cabbage moth) on Arabidopsis thaliana Col-0 and various
      glucosinolate-deficient mutants was investigated from hatching until pupation. We
      found that glucosinolates negatively affected larval growth and development, but
      not survival, with aliphatic glucosinolates having stronger effects than indolic
      glucosinolates, and the combination of the two glucosinolate types being even
      more detrimental to growth and development. Curiously, last instar larvae grew
      better on wild type than on non-glucosinolate-containing plant lines, but this
      could not be attributed to a change in detoxification rate or feeding behavior.
      Glucosinolates thus appear to be effective defenses against generalist
      lepidopteran herbivores at least during most stages of larval development.
      Nevertheless, the reversal of negative effects in the oldest instar is
      intriguing, and further investigation of this phenomenon may shed light on how
      generalists adjust their physiology to feed on diets with many different types of
      plant defense compounds.

PMID- 29209356
TI  - Corrigendum: Genetic Diversity, Population Structure, and Linkage Disequilibrium
      of an Association-Mapping Panel Revealed by Genome-Wide SNP Markers in Sesame.
AB  - [This corrects the article on p. 1189 in vol. 8, PMID: 28729877.].

PMID- 29209355
TI  - Flocculation of Chlamydomonas reinhardtii with Different Phenotypic Traits by
      Metal Cations and High pH.
AB  - Concentrating algal cells by flocculation as a prelude to centrifugation could
      significantly reduce the energy and cost of harvesting the algae. However, how
      variation in phenotypic traits such as cell surface features, cell size and
      motility alter the efficiency of metal cation and pH-induced flocculation is not
      well understood. Our results demonstrate that both wild-type and cell wall
      deficient strains of the green unicellular alga Chlamydomonas reinhardtii
      efficiently flocculate (>90%) at an elevated pH of the medium (pH 11) upon the
      addition of divalent cations such as calcium and magnesium (>5 mM). The trivalent
      ferric cation (at 10 mM) proved to be essential for promoting flocculation under
      weak alkaline conditions (pH ~8.5), with a maximum efficiency that exceeded 95
      and 85% for wild-type CC1690 and the cell wall-deficient sta6 mutant,
      respectively. Near complete flocculation could be achieved using a combination of
      5 mM calcium and a pH >11, while the medium recovered following cell removal
      could be re-cycled without affecting algal growth rates. Moreover, the absence of
      starch in the cell had little overall impact on flocculation efficiency. These
      findings contribute to our understanding of flocculation in different
      Chlamydomonas strains and have implications with respect to inexpensive methods
      for harvesting algae with different phenotypic traits. Additional research on the
      conditions (e.g., pH and metal ions) used for efficient flocculation of diverse
      algal groups with diverse characteristics, at both small and large scale, will
      help establish inexpensive procedures for harvesting cell biomass.

PMID- 29209357
TI  - HOTAIR: A Promising Long Non-coding RNA with Potential Role in Breast Invasive
      Carcinoma.

PMID- 29209358
TI  - Draft of Zucchini (Cucurbita pepo L.) Proteome: A Resource for Genetic and
      Genomic Studies.

PMID- 29209359
TI  - Wnt/beta-catenin Signaling Pathway Regulates Specific lncRNAs That Impact Dermal
      Fibroblasts and Skin Fibrosis.
AB  - Wnt/beta-catenin signaling is required for embryonic dermal fibroblast cell fate,
      and dysregulation of this pathway is sufficient to promote fibrosis in adult
      tissue. The downstream modulators of Wnt/beta-catenin signaling required for
      controlling cell fate and dermal fibrosis remain poorly understood. The discovery
      of regulatory long non-coding RNAs (lncRNAs) and their pivotal roles as key
      modulators of gene expression downstream of signaling cascades in various
      contexts prompted us to investigate their roles in Wnt/beta-catenin signaling.
      Here, we have identified lncRNAs and protein-coding RNAs that are induced by beta
      catenin activity in mouse dermal fibroblasts using next generation RNA
      sequencing. The differentially expressed protein-coding mRNAs are enriched for
      extracellular matrix proteins, glycoproteins, and cell adhesion, and many are
      also dysregulated in human fibrotic tissues. We identified 111 lncRNAs that are
      differentially expressed in response to activation of Wnt/beta-catenin signaling.
      To further characterize the role of mouse lncRNAs in this pathway, we validated
      two novel Wnt signaling- Induced Non-Coding RNA (Wincr) transcripts referred to
      as Wincr1 and Wincr2. These two lncRNAs are highly expressed in mouse embryonic
      skin and perinatal dermal fibroblasts. Furthermore, we found that Wincr1
      expression levels in perinatal dermal fibroblasts affects the expression of key
      markers of fibrosis (e.g., Col1a1 and Mmp10), enhances collagen contraction, and
      attenuates collective cell migration. Our results show that beta-catenin
      signaling-responsive lncRNAs may modulate dermal fibroblast behavior and collagen
      accumulation in dermal fibrosis, providing new mechanistic insights and nodes for
      therapeutic intervention.

PMID- 29209360
TI  - Assortative Mating by Ethnicity in Longevous Families.
AB  - Recent work shows strong evidence of ancestry-based assortative mating in spouse
      pairs of the older generation of the Framingham Heart Study. Here, we extend this
      analysis to two studies of human longevity: the Long Life Family Study (LLFS),
      and the New England Centenarian Study (NECS). In the LLFS, we identified 890
      spouse pairs spanning two generations, while in the NECS we used data from 102
      spouse pairs including offspring of centenarians. We used principal components of
      genome-wide genotype data to demonstrate strong evidence of ancestry-based
      assortative mating in spouse pairs of the older generation and also confirm the
      decreasing trend of endogamy in more recent generations. These findings in
      studies of human longevity suggest that spouses marrying into longevous families
      may not be powerful controls for genetic association studies, and that there may
      be important ethnicity-specific, genetic influences and/or gene-environment
      interactions that influence extreme survival in old generations. In addition, the
      decreasing trend of genetic similarity of more recent generations might have
      ramifications for the incidence of homozygous rare variants necessary for
      survival to the most extreme ages.

PMID- 29209361
TI  - Crotalus durissus terrificus crotapotin naturally displays preferred positions
      for amino acid substitutions.
AB  - Background: Classically, Crotalus durissus terrificus (Cdt) venom can be
      described, according to chromatographic criteria, as a simple venom, composed of
      four major toxins, namely: gyroxin, crotamine, crotoxin and convulxin. Crotoxin
      is a non-covalent heterodimeric neurotoxin constituted of two subunits: an active
      phospholipase A2 and a chaperone protein, termed crotapotin. This molecule is
      composed of three peptide chains connected by seven disulfide bridges. Naturally
      occurring variants/isoforms of either crotoxin or crotapotin itself have already
      been reported. Methods: The crude Cdt venom was separated by using RP-HPLC and
      the toxins were identified by mass spectrometry (MS). Crotapotin was purified,
      reduced and alkylated in order to separate the peptide chains that were further
      analyzed by mass spectrometry and de novo peptide sequencing. Results: The RP
      HPLC profile of the isolated crotapotin chains already indicated that the alpha
      chain would present isoforms, which was corroborated by the MS and tandem mass
      spectrometry analyses. Conclusion: It was possible to observe that the Cdt
      crotapotin displays a preferred amino acid substitution pattern present in the
      alpha chain, at positions 31 and 40. Moreover, substitutions could also be
      observed in beta and gamma chains (one for each). The combinations of these four
      different peptides, with the already described chains, would produce ten
      different crotapotins, which is compatible to our previous observations for the
      Cdt venom.

PMID- 29209362
TI  - Search for an Appropriate Behavior within the Emotional Regulation in Virtual
      Creatures Using a Learning Classifier System.
AB  - Emotion regulation is a process by which human beings control emotional
      behaviors. From neuroscientific evidence, this mechanism is the product of
      conscious or unconscious processes. In particular, the mechanism generated by a
      conscious process needs a priori components to be computed. The behaviors
      generated by previous experiences are among these components. These behaviors
      need to be adapted to fulfill the objectives in a specific situation. The problem
      we address is how to endow virtual creatures with emotion regulation in order to
      compute an appropriate behavior in a specific emotional situation. This problem
      is clearly important and we have not identified ways to solve this problem in the
      current literature. In our proposal, we show a way to generate the appropriate
      behavior in an emotional situation using a learning classifier system (LCS). We
      illustrate the function of our proposal in unknown and known situations by means
      of two case studies. Our results demonstrate that it is possible to converge to
      the appropriate behavior even in the first case; that is, when the system does
      not have previous experiences and in situations where some previous information
      is available our proposal proves to be a very powerful tool.

PMID- 29209363
TI  - A New Approach for Mobile Advertising Click-Through Rate Estimation Based on Deep
      Belief Nets.
AB  - In recent years, with the rapid development of mobile Internet and its business
      applications, mobile advertising Click-Through Rate (CTR) estimation has become a
      hot research direction in the field of computational advertising, which is used
      to achieve accurate advertisement delivery for the best benefits in the three
      side game between media, advertisers, and audiences. Current research on the
      estimation of CTR mainly uses the methods and models of machine learning, such as
      linear model or recommendation algorithms. However, most of these methods are
      insufficient to extract the data features and cannot reflect the nonlinear
      relationship between different features. In order to solve these problems, we
      propose a new model based on Deep Belief Nets to predict the CTR of mobile
      advertising, which combines together the powerful data representation and feature
      extraction capability of Deep Belief Nets, with the advantage of simplicity of
      traditional Logistic Regression models. Based on the training dataset with the
      information of over 40 million mobile advertisements during a period of 10 days,
      our experiments show that our new model has better estimation accuracy than the
      classic Logistic Regression (LR) model by 5.57% and Support Vector Regression
      (SVR) model by 5.80%.

PMID- 29209364
TI  - Genetic Algorithm for Traveling Salesman Problem with Modified Cycle Crossover
      Operator.
AB  - Genetic algorithms are evolutionary techniques used for optimization purposes
      according to survival of the fittest idea. These methods do not ensure optimal
      solutions; however, they give good approximation usually in time. The genetic
      algorithms are useful for NP-hard problems, especially the traveling salesman
      problem. The genetic algorithm depends on selection criteria, crossover, and
      mutation operators. To tackle the traveling salesman problem using genetic
      algorithms, there are various representations such as binary, path, adjacency,
      ordinal, and matrix representations. In this article, we propose a new crossover
      operator for traveling salesman problem to minimize the total distance. This
      approach has been linked with path representation, which is the most natural way
      to represent a legal tour. Computational results are also reported with some
      traditional path representation methods like partially mapped and order
      crossovers along with new cycle crossover operator for some benchmark TSPLIB
      instances and found improvements.

PMID- 29209365
TI  - Immune and Inflammatory Responses of the Intestinal Mucosa following Extended
      Liver Radiofrequency Ablation.
AB  - Background and Aim: Extended liver radiofrequency ablation (RFA) has been shown
      to disrupt gut barrier integrity with subsequent bacterial translocation. The aim
      of the present project was to study the immune and inflammatory responses of the
      intestinal mucosa after extended RFA of the liver. Methods: Twelve Wistar rats
      were either subjected to RFA of the left lateral hepatic lobe (approximately 30%
      of the liver mass) after midline laparotomy (group RFA, n = 6) or sham operation
      (group Sham, n = 6). Forty-eight hours later, ileal tissue specimens were excised
      for immunohistochemical assessment of CD68+ macrophages, CD4+ T-lymphocytes, CD8+
      T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor
      necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), and nuclear factor-kappaB
      (NFkappaB) expression. Results: Immune response biomarkers were upregulated in
      the RFA group. Expression of CD4+ and CD8+ T-lymphocytes was moderate, while that
      of CD68+ macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were
      also upregulated in the RFA group. TNFalpha, IL-6, and NFkappaB expression was
      low, moderate, and high, respectively. Conclusions: Extended liver RFA evokes
      both immune and inflammatory responses of the gut mucosa.

PMID- 29209366
TI  - Comment on "Identification of Differentially Expressed Genes in Pituitary
      Adenomas by Integrating Analysis of Microarray Data".

PMID- 29209367
TI  - Functional Characterization of Preadipocytes Derived from Human Periaortic
      Adipose Tissue.
AB  - Adipose tissue can affect the metabolic control of the cardiovascular system, and
      its anatomic location can affect the vascular function differently. In this
      study, biochemical and phenotypical characteristics of adipose tissue from
      periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were
      obtained from areas surrounding the ascending aorta and sternotomy incision,
      respectively. Adipose tissues were collected from patients undergoing myocardial
      revascularization or mitral valve replacement surgery. Morphological studies with
      hematoxylin/eosin and immunohistochemical assay were performed in situ to
      quantify adipokine expression. To analyze adipogenic capacity, adipokine
      expression, and the levels of thermogenic proteins, adipocyte precursor cells
      were isolated from periaortic and subcutaneous adipose tissues and induced to
      differentiation. The precursors of adipocytes from the periaortic tissue
      accumulated less triglycerides than those from the subcutaneous tissue after
      differentiation and were smaller than those from subcutaneous adipose tissue. The
      levels of proteins involved in thermogenesis and energy expenditure increased
      significantly in periaortic adipose tissue. Additionally, the expression levels
      of adipokines that affect carbohydrate metabolism, such as FGF21, increased
      significantly in mature adipocytes induced from periaortic adipose tissue. These
      results demonstrate that precursors of periaortic adipose tissue in humans may
      affect cardiovascular events and might serve as a target for preventing vascular
      diseases.

PMID- 29209368
TI  - Corrigendum to "Prevalence of Fracture Risk Factors in Postmenopausal Women
      Enrolled in the POSSIBLE US Treatment Cohort".
AB  - [This corrects the article DOI: 10.1155/2013/715025.].

PMID- 29209369
TI  - Detailed Componential Characterization of Extractable Species with Organic
      Solvents from Wheat Straw.
AB  - Componential analysis of extractives is important for better understanding the
      structure and utilization of biomass. In this investigation, wheat straw (WS) was
      extracted with petroleum ether (PE) and carbon disulfide (CS2) sequentially, to
      afford extractable fractions EFPE and EFCS2, respectively. Detailed componential
      analyses of EFPE and EFCS2 were carried out with Fourier transform infrared
      (FTIR) spectroscopy, gas chromatography/mass spectrometry (GC/MS), X-ray
      photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy
      dispersive spectrometry (EDS), and electron probe microanalysis (EPMA). Total
      extractives were quantified 4.96% by weight compared to the initial WS sample.
      FTIR and GC/MS analyses results showed that PE was effective for the extraction
      of ketones and waxes derived compounds; meanwhile CS2 preferred ketones and other
      species with higher degrees of unsaturation. Steroids were enriched into EFPE and
      EFCS2 with considerable high relative contents, namely, 64.52% and 79.58%,
      respectively. XPS analysis showed that most of the C atoms in extractives were
      contained in the structures of C-C, C-COOR, and C-O. TEM-EDS and EPMA analyses
      were used to detect trace amount elements, such as Al, Si, P, S, Cl, and Ca
      atoms. Detailed characterization of extractable species from WS can provide more
      information on elucidation of extractives in biomass.

PMID- 29209370
TI  - Cross-Cultural Validation of Urdu Version KOOS in Indian Population with Primary
      Knee Osteoarthritis.
AB  - Purpose: The primary aim of this study was to translate a self-reported
      questionnaire (KOOS) from English to Urdu and then to see its internal
      consistency, agreement, test-retest reliability, and validity among primary OA
      knee patients. Methodology: First, KOOS questionnaire was translated from English
      language to Urdu through standardized cross-cultural protocol. This translated
      version of KOOS was administered to 111 radiographically diagnosed primary OA
      knee patients at two times with 48-hour interval in-between. Cronbach's alpha,
      floor and ceiling effect, intraclass correlation coefficient (ICC), absolute
      agreement %, and Spearman correlation were used to fulfill our objectives.
      Results: Average time to administer this questionnaire was 20 minutes. There was
      good internal consistency with Cronbach's alpha ranging from 0.7246 to 0.9139.
      The absolute agreement of each item between two tests ranged from 81.08% to
      98.20%. Test-retest reliability was excellent ("r" ranged from 0.9673 to 0.9782).
      There was no ceiling effect; however less than 4% floor effect was seen in two
      subscales. There was significant difference that existed between different X-ray
      grades in all subscales meaning good content validity for disease prognosis.
      Conclusion: The present results show that KOOS Urdu version is a reliable and
      valid measure for primary OA knee patients.

PMID- 29209371
TI  - Corrigendum to "Dengue Virus NS1 Protein as a Diagnostic Marker: Commercially
      Available ELISA and Comparison to qRT-PCR and Serological Diagnostic Assays
      Currently Used by the State of Florida".
AB  - [This corrects the article DOI: 10.1155/2017/8072491.].

PMID- 29209372
TI  - Heat shock protein 27 plays a protective role in thoracic aortic dissection by
      promoting cell proliferation and inhibiting apoptosis.
AB  - Background: Thoracic aortic dissection (TAD) is one of the most severe aortic
      diseases. The study aimed to explore the potential role of heat shock protein 27
      (HSP27) in the pathogenesis of TAD using an in vitro model of oxidative stress in
      vascular smooth muscle cells (VSMCs). Methods: HSP27 was analyzed in aortic
      surgical specimens from 12 patients with TAD and 8 healthy controls. A lentiviral
      vector was used to overexpress HSP27 in rat aortic VSMCs. Cell proliferation and
      apoptosis were measured under oxidative stress induced by H2O2. Results: HSP27
      expression was significantly higher in aortic tissue from patients with TAD and
      VSMCs in the aortic media were the main cell type producing HSP27. Elevated
      oxidative stress was also detected in the TAD samples. Overexpression of HSP27
      significantly attenuated H2O2-induced inhibition of cell proliferation.
      Furthermore, HSP27 was found to decrease H2O2-induced cell apoptosis and
      oxidative stress. Conclusions: These results suggest that HSP27 expression
      promotes VSMC viability, suppresses cell apoptosis, and confers protection
      against oxidative stress in TAD.

PMID- 29209373
TI  - The Influence of Traditional Culture and the Interpersonal Psychological Theory
      on Suicide Research in Korea.
AB  - Korea has the highest suicide rate amongst the OECD countries. Yet, its research
      on suicidal behaviors has been primitive. While the Interpersonal Psychological
      Theory of Suicide has gained global attention, there has only been a few
      researches, which examined its applicability in Korea. In this article, we review
      the previous studies on suicide and examine the association between the
      Interpersonal Psychological Theory of Suicide and traditional Korean culture,
      with an emphasis on Collectivism and Confucianism. We propose that pathways to
      suicide might vary depending on cultural influences. Clinical implications and
      suggestions for future research will be discussed.

PMID- 29209374
TI  - Mental Health Assessment of South Korean Adults on Probation.
AB  - Objective: The association of offender mental illness (including those on
      probation) with crime has long been the subject of social interest; however,
      systematic management has been insufficient. The study purpose was to analyze
      mental illness prevalence, proportion of first offenses and recidivism with the
      mental illness of those on probation. Methods: A total of 206 adults on probation
      were divided into groups (first offenders and repeat offenders) and they
      completed self-report instruments and clinical interviews designed to diagnose
      mental illness. Results: The mental illness prevalence among those on probation
      was considerably higher than that of the general population, and having mental
      illness was related to re-sentencing probation or recidivism. In particular,
      alcohol use disorder, major depressive episode, manic/hypomanic episode, and
      antisocial personality disorder were shown to affect recidivism. Conclusion: To
      achieve the ultimate purpose of probation, social and systematic intervention on
      a mental health and medical basis may be required.

PMID- 29209375
TI  - Association of Anxiety, Depression, and Somatization with Menstrual Problems
      among North Korean Women Defectors in South Korea.
AB  - Objective: North Korean women defectors have suffered from anxiety, depression,
      and somatization after defection. Also they have had many menstrual problems like
      amenorrhea. This study was done to identify the correlations of anxiety,
      depression, and somatization to menstrual problems among North Korean woman
      defectors in South Korea. Methods: The participants in this study were 126 women
      from 5 government resettlement centers throughout South Korea. Questionnaires
      which included State-Trait Anxiety Inventory (STAI), Center for Epidemiological
      studies-Depression Scale (CED-S), and Symptom Checklist-90-Revised (SCL-90-R)
      were used to identify anxiety and somatization. Data were collected between June
      and September, 2012. Results: The women reported the following problems;
      amenorrhea (9.5%), hypomenorrhea (13.6%), menorrhagia (19.8%), polymenorrhea
      (13.5%), oligomenorrhea (4.8%), changes in amount of menstrual discharge (4.0%),
      and changes in amount of blood clot (9.5%). Anxiety (r=0.20, p=0.002), depression
      (r=0.25, p=0.005), and Somatization (r=0.35, p<0.001) were correlated with number
      of menstrual problems. Conclusion: The results of this study indicate that mental
      health services need to be taken into account in interventions for North Korean
      woman defectors to improve their reproductive health including addressing
      menstrual problems.

PMID- 29209376
TI  - Feasibility of Psychosocial Distress Screening and Management Program for
      Hospitalized Cancer Patients.
AB  - Objective: Although the diagnosis and treatment of cancer is associated with
      psychosocial distress, routine distress screening is difficult in hospitalized
      oncology settings. We developed a consecutive screening program for psychosocial
      distress to promote psychiatric treatment of cancer patients and evaluated the
      feasibility of our program by Distress Thermometer (DT) and Hospital Anxiety and
      Depression Scale (HADS). Methods: Among 777 cancer inpatients recruited from the
      Catholic Comprehensive Institute of Seoul St. Mary's Hospital, 499 agreed to
      complete primary distress screening through DT. We conducted secondary distress
      screening through HADS in 229 patients who had high scores of DT. Results: Of the
      499 participants, 270 patients with low scores of DT were included in the
      distress education program. 229 patients with high scores of DT received
      secondary distress screening through HADS. Among 115 patients with low scores of
      HADS, 111 patients received distress management. Among 114 patients with high
      scores in the secondary distress screening, 38 patients received psychiatric
      consultation service whereas 76 patients refused psychiatric consultation.
      Conclusion: Using consecutive screening for psychosocial distress appeared to be
      feasible in an inpatient oncology setting. Nevertheless, the low participation
      rate of psychiatric consultation service in cancer patients with high distress
      level should be improved.

PMID- 29209377
TI  - Pain in Patients with Dystrophic Epidermolysis Bullosa: Association with Anxiety
      and Depression.
AB  - Objective: We investigate the presence and the quality of pain in patients with
      dystrophic epidermolysis bullosa (DEB), and its correlation with the level of
      anxiety and depression. Methods: We collected data from 27 DEB patients and 26
      healthy individuals. DEB patients and controls completed 1 scale for the quality
      of pain, and 1 scale for anxiety and depression. Pain was assessed with the short
      form of the McGill Pain Questionnaire, whereas anxiety and depression were
      assessed with the Hamilton rating scale for anxiety and depression. Results: DEB
      patients and healthy control individuals were homogeneous for age and gender
      (p>0.05). A statistically significant difference in the two groups was seen for
      sensory pain rating scale (p<0.001), affective pain rating scale (p=0.029), total
      pain rating scale (p<0.001), visual analogue scale (p=0.012) and present pain
      intensity (p=0.001), but not for anxiety (p=0.169) and depression (p=0.530). The
      characteristics of pain that showed a significant difference between DEB patients
      and healthy controls were shooting, splitting, tender and throbbing (p<0.05). In
      DEB patients pain was not correlated with anxiety or depression (p>0.05), whereas
      a slight correlation between pain and anxiety was found in healthy controls
      (p<0.05). No difference was found between quality of pain and anxiety-depression
      in DEB patients (p>0.05), but was between the DEB dominant and the recessive form
      of DEB (p=0.025). Conclusion: The perception of pain in DEB patients appears
      greater than in healthy individuals, with splitting and tender characteristics
      being the most significant ones, but was not associated with anxious and/or
      depressive symptoms.

PMID- 29209378
TI  - Extrapyramidal Signs and Risk of Progression from Mild Cognitive Impairment to
      Dementia: A Clinical Research Center for Dementia of South Korea Study.
AB  - Objective: Extrapyramidal signs (EPS) are common in patients with mild cognitive
      impairment (MCI). However, few studies have assessed the effect of EPS on the
      clinical course of MCI. We aimed to evaluate whether patients with EPS show more
      frequent progression from MCI to Alzheimer's disease (AD) and to other types of
      dementia. Methods: Participants (n=882) with MCI were recruited, and were
      followed for up to 5 years. The EPS positive group was defined by the presence of
      at least one EPS based on a focused neurologic examination at baseline. Results:
      A total of 234 converted to dementia during the follow-up period. The risk of
      progression to AD was lower in the patients with EPS after adjusting for
      potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53
      0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of
      progression to dementia other than AD (HR=6.33, 95%CI=2.30-17.39, p<0.001).
      Conclusion: EPS in patients with MCI is a strong risk factor for progression of
      MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in
      patients with MCI can yield important clinical information for prognosis.

PMID- 29209379
TI  - Gender Differences in Suicidal Ideation and Related Factors among North Korean
      Refugees in South Korea.
AB  - Objective: According to previous social survey, a high number of North Korean
      refugees (NKRs) in South Korea had suicidal ideation. The purpose of this study
      is to examine the related factors for suicidal ideation among NKRs by gender in
      South Korea. Methods: We examined the sample of NKRs, 701 subjects (men=160,
      women=-541) residing in South Korea, the participants were enrolled from October
      2008 to May 2014. The related factors with suicidal ideation in NKRs were
      analyzed via a logistic regression analysis. Results: Refugee women were more
      likely to have suicidal ideation than men were. Although thoughts of suicide do
      not necessarily mean that they will follow through, however, there is an
      association that the higher rate of suicide also results in a higher rate of
      attempted suicide. In both genders, they tended to think more frequently about
      suicide who had stayed in South Korea for more than 5 years. In addition, higher
      frequencies of suicidal ideation also associated with higher level of perceived
      stress in both genders. Conclusion: The gender difference should be addressed
      when designing suicide prevention interventions among the North Korean population
      in South Korea.

PMID- 29209380
TI  - Health Care Utilization and Expenditures of Patients with Diabetes Comorbid with
      Depression Disorder: A National Population-Based Cohort Study.
AB  - Objective: The study investigated to compare health care utilization and
      expenditures between diabetic patients with and without depression in Taiwan.
      Methods: Health care utilization and expenditure among diabetic patients with and
      without depression disorder during 2000 and 2004 were examined using Taiwan's
      population-based National Health Insurance claims database. Health care
      utilization included outpatient visits and the use of inpatient services, and
      health expenditures were outpatient, inpatient, and total medical expenditures.
      Moreover, general estimation equation models were used for analyzing the factors
      associated with outpatient visits and expenditures. Multiple logistic regression
      analysis was applied for identifying the factors associated with hospitalization.
      Results: The average annual outpatient visits and annual total medical
      expenditures in the study period were 44.23-52.20; NT$87,496-133,077 and 30.75
      32.92; NT$64,411-80,955 for diabetic patients with and without depression. After
      adjustment for covariates, our results revealed that gender and complication were
      associated with out-patient visits. Moreover, the time factor was associated with
      the total medical expenditure, and residential urbanization and complication
      factors were associated with hospitalization. Conclusion: Health care utilization
      and expenditures for diabetic patients with depression were significantly higher
      than those without depression. Sex, complications, time, and urbanization are the
      factors associated with health care utilization and expenditures.

PMID- 29209382
TI  - Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in
      Patients with Schizophrenia.
AB  - Objective: The present, case-control, study investigates binaural hearing
      performance in schizophrenia patients towards sentences presented in quiet and
      noise. Methods: Participants were twenty-one healthy controls and sixteen
      schizophrenia patients with normal peripheral auditory functions. The binaural
      hearing was examined in four listening conditions by using the Malay version of
      hearing in noise test. The syntactically and semantically correct sentences were
      presented via headphones to the randomly selected subjects. In each condition,
      the adaptively obtained reception thresholds for speech (RTS) were used to
      determine RTS noise composite and spatial release from masking. Results:
      Schizophrenia patients demonstrated significantly higher mean RTS value relative
      to healthy controls (p=0.018). The large effect size found in three listening
      conditions, i.e., in quiet (d=1.07), noise right (d=0.88) and noise composite
      (d=0.90) indicates statistically significant difference between the groups.
      However, noise front and noise left conditions show medium (d=0.61) and small
      (d=0.50) effect size respectively. No statistical difference between groups was
      noted in regards to spatial release from masking on right (p=0.305) and left
      (p=0.970) ear. Conclusion: The present findings suggest an abnormal unilateral
      auditory processing in central auditory pathway in schizophrenia patients. Future
      studies to explore the role of binaural and spatial auditory processing were
      recommended.

PMID- 29209381
TI  - Do Patients Want to Listen to a Diagnosis of Dementia in Korea? Preferences on
      Disclosing a Diagnosis of Dementia and Discussing Advance Care Planning in
      Elderly Patients with Memory Concerns and Their Families.
AB  - Objective: In this study, we aimed to investigate preferences regarding the
      disclosure of a dementia diagnosis and advance care planning (ACP) in patients
      with memory complaints and their families. Methods: A total of 98 patients who
      visited the department of psychiatry at a tertiary hospital with memory
      complaints and 62 family members completed a structured questionnaire. The
      questionnaire included preferences on disclosure of dementia and cancer
      diagnosis, awareness and preferences on ACP. Results: In total, 96.9% of patients
      were willing to know their dementia diagnosis. There were no significant
      differences in preferences between the diagnosis of cancer and dementia. Only
      24.7% of patients and 45.8% of family members have heard of ACP. However, 82.8%
      of patients agreed on the necessity of ACP under the current condition.
      Multivariate analysis revealed that younger patients were more likely to agree
      with necessity for ACP under the current condition. Conclusion: In Korea,
      patients with memory complaints and their family members strongly favored a
      disclosure of dementia diagnosis. The majority of participants also agreed on the
      necessity of ACP. More active involvement of patients is needed in treatment
      decisions and care planning in cases of dementia as well as other life
      threatening illnesses.

PMID- 29209383
TI  - Psychological Problems of Pneumothorax According to Resilience, Stress, and Post
      Traumatic Stress.
AB  - Objective: The aims of the study were to investigate psychological distress in
      pneumothorax patients. Methods: A cohort study was performed in 101 patients with
      spontaneous pneumothorax. They were divided into three groups: (A) under 19 years
      old, (B) those of an intermediate age, and (C) over 45 years old. General well
      being [Psychological Wellbeing Index-Short Form (PWI-SF)], traumatic event
      [Impact of Event Scale (IES)], and resilience [Life Orientation Test-Revised (LOT
      R)] were assessed. Results: There were 35 patients in Group A, 51 in B, and 15 in
      C. The mean length of hospital stay was five days in all patients. The overall
      recurrence rate after surgery was 8%. All patients were under severe stress and
      reported an average PWI-SF score of 39. The IES score was 27, which did not meet
      the criteria for post-traumatic stress disorder but was higher in Group C than in
      the other groups (p=0.02). Age and operation were significant factors for a high
      IES, but age was the only significant factor according to multivariate analysis.
      Conclusion: Pneumothorax patients may be at high risk for severe stress.
      Moreover, post-traumatic stress was higher in elderly patients. Actions to reduce
      the psychological problems in these patients are required.

PMID- 29209384
TI  - Association between Healthcare Utilization and Depression in Korean Women with
      Cardiovascular Conditions.
AB  - Objective: This study aimed to examine the associations between depression and
      both coronary artery disease (CAD) and cardiovascular risk factors (CVRs) in
      Korean women. Furthermore, this study sought to determine whether depression was
      associated with use of healthcare services in women with CAD or CVRs. Methods:
      This cross-sectional study was conducted on 26,335 women who were aged 19 years
      or older, and who participated in the Korean National Health and Nutrition
      Examination Survey (2007-2014). Associations of prior diagnosis of depression
      with CAD and CVRs and with nonutilization of healthcare services were
      investigated. Results: Women with depression had a higher prevalence of CAD and
      CVRs including obesity, hypertension, dyslipidemia, and metabolic syndrome than
      those without depression. In addition, depression was significantly associated
      with nonutilization of healthcare services in women with most CVRs. Conclusion:
      Considering the high rate of comorbid depression with CAD or CVRs and the low
      lvels of health service utilization in depressed patients, screening for common
      CVRs, such as obesity, hypertension, and dyslipidemia, should be provided for
      patients with depression in mental health care settings.

PMID- 29209385
TI  - The Role of Uncontrolled Eating and Screen Time in the Link of Attention Deficit
      Hyperactivity Disorder with Weight in Late Childhood.
AB  - Objective: The aim of this study was to examine the mediating roles of
      uncontrolled eating and sedentary behaviours in the link of attention deficit
      hyperactivity disorder (ADHD) and weight. Methods: A total of 352 children in
      fifth and sixth grade participated in the present study by completing the self
      rated Three-Factor Eating Questionnaire and Children of Alcoholics Screening Test
      during regular classes. An additional questionnaire completed by their parents
      provided information about the children's ADHD and emotional symptoms, sedentary
      behaviour based on screen time, and parental variables. The questionnaires were
      surveyed within one week after their schools' annual physical check-up. Results:
      Hierarchical regression analyses revealed that uncontrolled eating was complete
      mediator in association between ADHD symptoms and body mass index (BMI) for boys,
      incomplete mediator for girls. However, screen time had no significant effect on
      the ADHD symptoms-BMI link for both gender. Conclusion: The findings of this
      study suggest that gender specific intervention programs may be need to help
      eating behaviour in children with ADHD and overweight.

PMID- 29209386
TI  - Medical and Psychiatric Comorbidities in Korean Children and Adolescents with
      Attention-Deficit/Hyperactivity Disorder.
AB  - Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with a
      high rate of comorbid disorders. We aimed to investigate the medical and
      psychiatric comorbidities of Korean children and adolescents with ADHD. Methods:
      Data were obtained from Korean National Health Insurance Review and Assessment
      Service-National Patient Sample (HI-RA-NPS) for 2011. We included 2,140 (mean
      age, 10.9+/-3.1 years; boys, 1,710) and 219,410 (non-ADHD; mean age, 12.4+/-3.7
      years; boys, 113,704) children and adolescents with and without ADHD,
      respectively. We compared medical and psychiatric comorbidities between the
      groups, and performed weighted logistic regression analyses to obtain odds ratios
      (ORs) and 95% confidence intervals (CIs). Results: Most medical comorbidities
      were more likely in patients with ADHD and included nervous system disease (OR,
      2.59; 95% CI, 2.52-2.66); endocrine, nutritional, and metabolic disease (OR,
      2.09; 95% CI, 2.04-2.15); and congenital malformations, deformations, and
      chromosomal abnormalities (OR, 2.00; 95% CI, 1.90-2.11). Oppositional defiant
      disorder and conduct disorder were more prevalent in patients with ADHD (OR,
      81.88; 95% CI, 79.00-84.86), followed by learning (OR, 75.61; 95% CI, 69.69
      82.04), and depressive disorders (OR, 55.76; 95% CI, 54.44-57.11). Conclusion:
      Our results suggest that Korean children and adolescents with ADHD are more
      likely to suffer medical and psychiatric comorbidities than those without ADHD.

PMID- 29209387
TI  - Spicy Food Preference and Risk for Alcohol Dependence in Korean.
AB  - Objective: Previous studies have reported that both preference for spicy food and
      drinking behavior are associated with the activity of the opioid system in the
      central nervous system. The relationship between the preference for spicy food
      and the risk of alcohol dependence by comparing spicy food preference in alcohol
      dependent patients vs. healthy controls was investigated. Also the association
      between the preference for spicy food and OPRM1 A118G was studied. Methods: A
      total of 150 Korean male patients with alcohol dependence and 100 normal male
      control subjects were included in this study. Preference for spicy food was
      measured using the Food Preference Scale (FPS). DNA analysis was conducted to
      detect the A118G polymorphism. Results: The mean FPS score was significantly
      higher in the alcohol-dependent patients (61.2+/-24.2) than in the normal control
      subjects (53.0+/-22.0). FPS scores differed significantly between alcohol
      dependent patients and normal control subjects who had the G allele in OPRM1
      A118G, but not between the two groups with the AA genotype. Conclusion: A strong
      preference for spicy food can be assumed to be a risk factor for alcohol
      dependence, particularly in those carrying the G allele in OPRM1 A118G.

PMID- 29209388
TI  - A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless
      Legs Syndrome in a Korean Population.
AB  - Objective: Restless legs syndrome (RLS) is a highly heritable and common
      neurological sensorimotor disease disturbing sleep. The objective of study was to
      investigate significant gene for RLS by performing GWA and replication study in a
      Korean population. Methods: We performed a GWA study for RLS symptom group
      (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We
      subsequently performed a replication study in RLS and normal controls (227 RLS
      and 229 controls) to confirm the present GWA study findings as well as previous
      GWA study results. Results: In the initial GWA study of RLS, we observed an
      association of rs11645604 (OR=1.531, p=1.18*10-6) in MPHOSPH6 on chromosome
      16q23.3, rs1918752 (OR=0.6582, p=1.93*10-6) and rs9390170 (OR=0.6778, p=7.67*10
      6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170
      in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046,
      respectively) were significantly associated with RLS. Moreover, we found the
      haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69*10
      18) in BTBD9 was associated with RLS. Conclusion: From our sequential GWA and
      replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel
      genetic marker for susceptibility to RLS. Regarding with utrophin, which is
      encoded by UTRN, is preferentially expressed in the neuromuscular synapse and
      myotendinous junctions, we speculate that utrophin is involved in RLS,
      particularly related to the neuromuscular aspects.

PMID- 29209389
TI  - Asymmetrical Electroencephalographic Change of Human Brain During Sleep Onset
      Period.
AB  - Objective: Human cerebral hemisphere is known to function asymmetrically with
      daytime left hemisphere superiority in most right-handed persons. It may have
      relevance to the localization of specific function of the brain. This study
      attempted to reveal whether the functional cerebral asymmetry in the wakeful
      state is still maintained throughout the sleep onset period. Methods: Thirty
      channel EEG was recorded in 61 healthy subjects. The EEG power spectra of each of
      the seven frequencies were compared between the two kinds of 30-second states;
      the wakeful stage and the late-sleep stage 1. Results: The asymmetrical indices
      of sleep stage 1 at several fronto-central leads were decreased in the delta,
      theta, alpha-2, and all beta bands. Conversely, at parts of parieto-occipital
      leads showed an increase in the indices of the theta, alphas, beta-1, and beta-2
      bands. Any fronto-central leads did not show an increase in the index, and no
      parieto-occipital leads showed a decrease. Conclusion: During the sleep onset
      period, power spectral asymmetry of the brain showed a different pattern from the
      wakeful stage. This asymmetrical pattern of EEG powers may suggest a reversal of
      the left hemispheric dominance during sleep.

PMID- 29209390
TI  - The Mechanism of Anti-Epileptogenesis by Levetiracetam Treatment is Similar to
      the Spontaneous Recovery of Idiopathic Generalized Epilepsy during Adolescence.
AB  - Objective: The anti-epileptogenic drug levetiracetam has anticonvulsant and anti
      epileptogenesis effects. Synergy between cell death and inflammation can lead to
      increased levels of apoptosis inhibitory factors and brain-derived neurotrophic
      factor, aberrant neurogenesis and extended axon sprouting. Once hyperexcitation
      of the neural network occurs, spontaneous seizures or epileptogenesis develops.
      This study investigated whether the anti-epileptogenic effect of levetiracetam is
      due to its alternate apoptotic activity. Methods: Adult male Noda epileptic rats
      were treated with levetiracetam or vehicle control for two weeks. mRNA
      quantification of Bax, Bcl-2 and GAPDH expression were performed from prefrontal
      cortex and hippocampus tissue samples. Results: The levetiracetam-treated group
      showed a significant increase of Bax/Bcl-2 mRNA expression ratio in the
      prefrontal cortex than the control group, but no change in the Bax/Bcl-2 mRNA
      expression ratio in hippocampus. Conclusion: Idiopathic generalized epilepsy
      including childhood absence epilepsy develop at childhood and recover
      spontaneously during adolescence. The aberrant neural excitable network is pruned
      by a neural-maturing action. This study suggests the mechanism of acquired anti
      epileptogenesis by levetiracetam treatment may be similar to spontaneous recovery
      of idiopathic generalized epilepsy during adolescence.

PMID- 29209391
TI  - Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's
      Disease: Methodology and Baseline Sample Characteristics.
AB  - Objective: The Korean Brain Aging Study for the Early Diagnosis and Prediction of
      Alzheimer's disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90
      years, to search for new biomarkers of Alzheimer's disease (AD) and to
      investigate how multi-faceted lifetime experiences and bodily changes contribute
      to the brain changes or brain pathologies related to the AD process. Methods: All
      participants received comprehensive clinical and neuropsychological evaluations,
      multi-modal brain imaging, including magnetic resonance imaging, magnetic
      resonance angiography, [11C]Pittsburgh compound B-positron emission tomography
      (PET), and [18F]fluorodeoxyglucose-PET, blood and genetic marker analyses at
      baseline, and a subset of participants underwent actigraph monitoring and
      completed a sleep diary. Participants are to be followed annually with clinical
      and neuropsychological assessments, and biannually with the full KBASE
      assessment, including neuroimaging and laboratory tests. Results: As of March
      2017, in total, 758 individuals had volunteered for this study. Among them, in
      total, 591 participants-291 cognitively normal (CN) old-aged individuals, 74 CN
      young- and middle-aged individuals, 139 individuals with mild cognitive
      impairment (MCI), and 87 individuals with AD dementia (ADD)-were enrolled at
      baseline, after excluding 162 individuals. A subset of participants (n=275)
      underwent actigraph monitoring. Conclusion: The KBASE cohort is a prospective,
      longitudinal cohort study that recruited participants with a wide age range and a
      wide distribution of cognitive status (CN, MCI, and ADD) and it has several
      strengths in its design and methodologies. Details of the recruitment, study
      methodology, and baseline sample characteristics are described in this paper.

PMID- 29209392
TI  - Comparative Analysis of Emotional Symptoms in Elderly Koreans with Hwa-Byung and
      Depression.
AB  - Objective: This study compared the symptomatic emotional traits of elderly South
      Korean patients with hwa-byung and those with depression. Methods: We enrolled 58
      patients with hwa-byung, 180 patients with depression, and 181 healthy control
      subjects. All participants completed the Hwa-byung Scale, Hamilton Depression
      Rating Scale (HDRS), Beck Depression Inventory (BDI), Geriatric Depression Scale
      (GDS), State Trait Anger Expression Inventory (STAXI), Reaction Inventory (RI),
      and Aggression Questionnaire (AQ). Chi-square tests and a one-way analysis of
      variance with Games-Howell post-hoc tests were used to compare demographic
      variables and scores. Results: A binary logistic regression analysis was used to
      examine risk factors for hwa-byung. Scores in the hwa-byung group were higher
      than those in the depression group for the HDRS; BDI; GDS; trait anger STAXI
      subscale (trait anger temperament and trait anger reaction); state anger and
      anger expression STAXI subscales (anger-in, anger-out, and anger control);
      physical and verbal aggression as well as anger and hostility AQ subscales; and
      disturbance, embarrassing circumstances, personal disrespect, and unpleasant
      encounters RI subscales. A binary logistic regression analysis demonstrated that
      the state anger STAXI subscale, verbal aggression and anger AQ subscales, and
      unpleasant encounters RI subscale were significantly associated with hwa-byung.
      Conclusion: Elderly patients with hwa-byung had more severe anger traits and
      states as well as higher depression severity compared to those diagnosed with
      clinical depression. Excessive anger and anger reactivity to unpleasant factors
      may be risk factors for hwa-byung, whereas the appropriate expression (rather
      than suppression) of anger may decrease the risk of hwa-byung.

PMID- 29209393
TI  - Relationship between Problematic Internet Use and Post-Traumatic Stress Disorder
      Symptoms among Students Following the Sewol Ferry Disaster in South Korea.
AB  - We investigated the association between problematic internet use (PIU) and post
      traumatic stress disorder (PTSD) symptoms in children and adolescents in South
      Korea. A cross-sectional survey was administered to community students who
      attended primary, secondary, and high schools in the Jindo area 1-2.5 months
      after the Sewol ferry disaster. Of the 1,744 respondents, 392 students who were
      exposed to the disaster, witnessing the rescue work directly, were evaluated.
      PTSD symptoms were measured using the University of California Los Angeles Post
      traumatic Stress Disorder Reaction Index (UCLA PTSD-RI). The severity of
      impairment caused by excessive internet use was evaluated using Young's Internet
      Addiction Test. The Center for Epidemiological Studies Depression Scale (CES-D)
      and State Anxiety Inventory for Children (SAIC) were also used. Logistic
      regression analysis revealed that PIU was significantly and independently
      associated with a high level of PTSD symptoms. Our findings suggest that children
      and adolescents with PIU require intensive follow-up and special care to prevent
      the development of PTSD symptoms following a disaster.

PMID- 29209394
TI  - Polymorphism in the Promoter Region of SEMA5A Is Associated with Sociality Traits
      in Korean Subjects with Autism Spectrum Disorders.
AB  - In this study, we evaluated the association between autism spectrum disorders
      (ASDs) and 10 single-nucleotide polymorphisms (SNPs) in the 5' region of the
      semaphorin 5A gene (SEMA5A) for 250 Korean trios including children with ASDs.
      Family-based association testing and haplotype analysis revealed a statistically
      significant association between rs194085 and multiple sociality traits with
      Korean ASDs in the dominant model (p<0.001, corrected p=0.035). This indicates
      that genetic variations in the 5' region of SEMA5A play a role in the genetic
      predisposition to sociality traits in Korean ASDs.

PMID- 29209395
TI  - Prevalence and Psychiatric Comorbidities of Internet Addiction in a Nationwide
      Sample of Korean Adults.
AB  - The goal of the study was to examine the prevalence and psychiatric comorbidities
      of Internet addiction in a nationwide sample of Korean adults. Among a total of
      6,022 participants involved in Korean Epidemiological Catchment Area study in
      2011, 3,723 Internet users were assessed for their Internet addiction using
      Young's 8-item Diagnostic Questionnaire. The results showed that of the 3,723
      Internet users, 39 (1.0%) had Internet addiction. Addicted Internet users were
      younger, more likely to be males and unemployed compared to non-addicted Internet
      users. Internet addiction was associated with alcohol and nicotine use disorders,
      depressive disorders, and anxiety disorder after controlling for age, gender, and
      occupational status. Internet addiction was associated with suicidal plans even
      after controlling for psychiatric disorders and socio-demographic factors. This
      study showed that Internet addiction is highly associated with variety of
      different psychiatric disorders and suicidal plans. Therefore, clinicians should
      carefully evaluate them when treating addicted Internet users.

PMID- 29209396
TI  - Whole Brain Voxel-Wise Analysis of Cerebral Retention of Beta-Amyloid in
      Cognitively Normal Older Adults Using 18F-Florbetaben.
AB  - Objective: Recently developed 18F-labelled amyloid beta (Abeta) positron emission
      tomography (PET) tracers have demonstrated potentials to enable more prevalent
      application of amyloid imaging in the clinical setting. The aim of this study is
      to demonstrate cerebral retention of Abeta in cognitively normal older adults, by
      implementing voxel-based analysis on images acquired from 18F-Florbetaben amyloid
      PET. Methods: Fifty cognitive normal elderly subjects were recruited and included
      in the study. Demographic data and cognitive measurements were collected.
      Magnetic resonance imaging (MRI) and 18F-Florbetaben PET data were obtained
      followed by whole brain voxel-based analysis. Results: Compared to the
      florbetaben (FBB) (-) counterpart, FBB (+) showed significantly higher Abeta
      deposition in the brain regions comprising anterior cingulate, middle cingulate,
      posterior cingulate and precuneus (family wise error corrected p<0.05). There was
      no significant correlation between amyloid retention and cognitive functions.
      Conclusion: Our results confirms previous results regarding Abeta deposition by
      using 18F-Florbetaben, demonstrating potentials in application of 18F-Florbetaben
      PET imaging in clinical settings.

PMID- 29209397
TI  - Individuals with Restless Legs Syndrome Tend to have Severe Depressive Symptoms:
      Findings from a Community-Based Cohort Study.
AB  - Restless legs syndrome (RLS) is a sensorimotor neurological disturbance causing
      physical and psychological distress. Here, we investigated the severity and
      effect of depressive symptoms in RLS among a Korean cohort population. Depressive
      symptoms were more prevalent in the RLS group than in the non-RLS group [>=mild
      depression: odds ratio (OR)=1.95, p<0.001; >= moderate depression: OR=6.15,
      p<0.001; and >=severe depression: OR=56.54, p<0.001], with a predominant
      proportion of severe depression (97%) in the RLS group. We found that difficulty
      falling asleep (OR=8.16, p<0.001), broken sleep (OR=11.66, p=0.001), early
      morning awakening (OR=8.5, p<0.001), and excessive daytime sleepiness (OR=3.04,
      p=0.031) were significantly frequent in individuals with severe depression in the
      RLS group. Red blood cell count was significantly low in individuals with severe
      depression in the RLS group (p=0.041). We found that severe depression was
      associated with RLS, suggesting the evaluation and management of mood symptoms
      and sleep-related and hematological features when treating RLS.

PMID- 29209398
TI  - Risk Factors Associated with the Fear of Falling in Community-Living Elderly
      People in Korea: Role of Psychological Factors.
AB  - Little is known about the risk factors for the fear of falling in elderly Korean
      individuals. Thus, the present study aimed to investigate the risk factors for
      fear of falling in a representative elderly population of over 10,000 individuals
      aged 65 years and older. A multivariate multinomial analysis revealed that the
      risk factors associated with a severe fear of falling were being female [odds
      ratio (OR)=4.396], older age (OR=5.550 for those aged >=85 years), lower level of
      education (OR=0.719 for those with >=13 years of schooling), chronic illness
      (OR=2.788 for those with more than three chronic illnesses), poor subjective
      health (OR=6.268), functional impairments (OR=2.340), a history of falling
      (OR=7.062), and depression (OR=1.774). The ORs for each of these risk factors
      were particularly high in participants with a severe fear of falling.
      Particularly, a history of falling and/or poor subjective health status had
      strong independent associations with the fear of falling. The present findings
      may help health care professionals identify individuals that would benefit from
      interventions aimed at reducing the fear of falling.

PMID- 29209399
TI  - Psychiatric Symptoms in Teachers from Danwon High School after Exposure to the
      Sinking of the Motor Vessel Sewol.
AB  - Objective: The goal of this study was to describe the psychiatric symptoms in the
      teachers from Danwon High School who were exposed to the sinking of the Motor
      Vessel Sewol. Methods: Data were collected from 32 teachers who underwent
      psychiatric interventions by 16 volunteer psychiatrists for 3 months after the
      sinking of the Motor Vessel Sewol. Results: The most commonly diagnosed clinical
      diagnosis in the teachers were normal reaction, acute stress disorder and
      adjustment disorder. Psychiatric symptoms including anxiety, depressed mood and
      sleep disturbances were also observed. Conclusion: In the acute aftermath of the
      Sewol Ferry sinking on April 16, 2014, psychiatrists volunteered to provide
      professional psychiatric interventions to Danwon High School teachers. These
      results suggest the importance of crisis intervention focused on the teachers who
      are exposed to disasters. The implications for future research and interventions
      are discussed.

PMID- 29209400
TI  - Frontal Lobe Dysfunction in a Depressed Patient Who Survived a Suicide Attempt by
      Jumping from the Bridge on the Han River.
AB  - Suicide attempts at the Han river are rapidly increasing, which are 4.11 times
      from 2005 to 2015, whereas the rate of completed suicide in South Korea increased
      1.07 times during the same period. However, few studies have been conducted on
      the issue because many suicide attempters were seriously injured after a fall in
      the Han river. We present a case of a patient with major depressive disorder
      (MDD) who attempted suicide and minimally injured after jumping from the bridge
      at the Han river. We could assess his psychological and neurocognitive functions
      before and immediately after his attempt. From this case, we can identify that
      higher cognitive aspect of executive dysfunction, especially in the frontal
      domain of selective attention and inhibition, may be associated with his suicide
      attempt. In conclusion, we suggest psychiatric treatments for cognitive
      impulsiveness and safety barriers at the bridge to prevent suicide attempts of
      patients with MDD.

PMID- 29209401
TI  - ACP1 Gene Polymorphism Associated with Suicide Attempt Type in Bipolar Disorder
      Patients.

PMID- 29209402
TI  - Analgesics in the management of behavioral and psychological symptoms of
      dementia: a perspective review.
AB  - The objective of this review was to assess the efficacy and tolerability of
      analgesics in reducing behavioral and psychological symptoms of dementia (BPSD)
      among older adults from published randomized controlled trials (RCTs). A
      literature search was conducted of PubMed, MEDLINE, SCOPUS, PsycINFO, and
      Cochrane collaboration databases for RCTs in the English language that evaluated
      the use of analgesics in reducing the severity of BPSD among older adults.
      Additionally, references of full-text articles that were included in this review
      were searched for extra studies. We identified a total of three unique RCTs that
      evaluated the use of analgesics among individuals with BPSD. One of the
      identified RCTs resulted in a total of three additional published papers in the
      literature, resulting in a total of six papers to be included in this review. All
      three RCTs identified some benefit for the use of analgesics in reducing BPSD.
      The analgesics appeared to be well tolerated in the included studies. Major study
      limitations include the use of data exclusively from published RCTs and limiting
      the search to English language publications. Additionally, we did not utilize
      statistical methods to evaluate the treatment outcomes including tolerability. In
      conclusion, available evidence although limited indicates that analgesics may
      reduce BPSD among some individuals with dementia living in nursing homes and are
      well tolerated.

PMID- 29209404
TI  - Response to discrepancies in publications related to HMB-FA and ATP
      supplementation.
AB  - Gentles and Phillips have submitted questions regarding three recent papers
      investigating ATP, HMB and the combination. The questions pertaining to the
      homogeneity of subjects' characteristics between the three different published
      papers, and why there appears to be differences in the number of subjects in
      placebo groups across studies. This response addresses each of these issues and
      demonstrates that there are no discrepancies between papers but rather a
      misunderstanding of the papers previously published.

PMID- 29209403
TI  - Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin
      type 9 (PCSK9): an emerging chapter in lipid-lowering therapy.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that
      is mainly expressed in the liver but can also be found in the intestine and
      kidneys. PCSK9 promotes the degradation of low density lipoprotein receptors
      (LDLR) by reducing their recycling and targeting the receptors for lysosomal
      destruction, thereby decreasing the rate of removal of LDL-cholesterol from the
      circulation. Thus, interventions targeting PCSK9 by reducing its expression may
      lead to significant reductions of LDL-cholesterol and possibly decrease
      cardiovascular risk. The present review aims to present and discuss the current
      clinical and scientific data pertaining to lipid-lowering interventions targeting
      PCSK9.

PMID- 29209405
TI  - Retroconversion is a minor contributor to increases in eicosapentaenoic acid
      following docosahexaenoic acid feeding as determined by compound specific isotope
      analysis in rat liver.
AB  - Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue
      levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally
      believed that this increase is due to DHA retroconversion to EPA, however, a
      slower conversion of alpha-linolenic acid (ALA, 18:3n-3) derived EPA to
      downstream metabolic products (i.e. slower turnover of EPA) is equally plausible.
      In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA +
      ALA diet for 12 weeks. Afterwards, livers were collected and the natural
      abundance 13C-enrichment was determined by compound specific isotope analysis
      (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary
      ALA and DHA 13C-enrichment. Isotopic signatures (per mil, 0/00) for liver EPA
      were not different (p > 0.05) between the ALA only diet (-25.89 +/- 0.39 0/00,
      mean +/- SEM) and the DHA + ALA diet (-26.26 +/- 0.40 0/00), suggesting the
      relative contribution from dietary ALA and DHA to liver EPA did not change.
      However, with DHA feeding estimates of absolute EPA contribution from ALA
      increased 4.4-fold (147 +/- 22 to 788 +/- 153 nmol/g) compared to 3.2-fold from
      DHA (91 +/- 14 to 382 +/- 13 nmol/g), respectively. In conclusion, CSIA of liver
      EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of
      DHA to EPA is a relatively small contributor to increases in EPA, and that this
      increase in EPA is largely coming from elongation/desaturation of ALA.

PMID- 29209406
TI  - Serum prolactin levels and sexual dysfunction in patients with schizophrenia
      treated with antipsychotics: comparison between aripiprazole and other atypical
      antipsychotics.
AB  - Objectives: Antipsychotics, even atypical ones, can induce hyperprolactinemia.
      Aripiprazole (APZ), a dopamine D2 partial agonist, has a unique pharmacological
      profile and few side effects. We investigated the incidence of hyperprolactinemia
      in patients with schizophrenia treated with APZ and other antipsychotics.
      Methods: Serum prolactin levels were measured by ELISA (enzyme-linked
      immunosorbent assay). A questionnaire survey was used to evaluate subjective
      sexual dysfunction. Results: Based on the results of the questionnaire,
      approximately half (48.1%) of the patients complained of sexual dysfunction. The
      serum prolactin levels were significantly higher in patients with sexual
      dysfunction than in those without. In patients treated with antipsychotic
      monotherapy, the serum prolactin levels were significantly lower in patients
      treated with APZ than with other antipsychotics. In patients receiving 2 or more
      antipsychotics, the serum prolactin levels were significantly lower in patients
      treated with APZ-containing regimens than in patients treated with APZ-free
      regimens. Conclusions: Treatment with APZ did not influence the serum prolactin
      level, and adjunctive treatment with APZ may ameliorate the hyperprolactinemia
      that occurs during monotherapy with other antipsychotics.

PMID- 29209407
TI  - Heavy metals effect on breast cancer progression.
AB  - Background: Breast cancer is the most frequent localization of malignant process
      in American women and women of European countries. To date it is not possible to
      control the morbidity growth due to lack of effective ways of primary prevention.
      Comparing the incidence of breast cancer in developed countries with the
      countries of Asia and Africa, there is the fact of population predominance lesion
      in more urbanized countries. This suggests that the environment along with other
      factors, occupies a significant place in the initiation and progression of breast
      neoplasia. The impressive rates of industrial development led to the pollution of
      soil, surface water and, as a consequence, food by heavy metal salts.The purposes
      of this paper are as follows: the chemical composition determination of
      neoplastic breast tissue, evaluation of the DNA methylation level, study of
      prognostic-important receptors expression in the breast cancer cells,
      establishing linkages between all the derived indicators. Methods: In our study
      we used the following methods: studying of the chemical composition of breast
      cancer tissue by atomic absorption spectrophotometry and energy-dispersion
      spectrometer; immunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E
      cadherin and MGMT receptors; DNA extraction and investigation by oscillating
      infrared spectroscopy method. Results: The total amount of heavy metals in breast
      cancer tissue ranged from 51.21 * 10-3 to 84.86 * 10-3 MUg/kg. We have got the
      following results: the growth of heavy metals in neoplastic tissue is accompanied
      with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and
      PR expression. The increment of pathological DNA methylation is accompanied with
      the increasing amount of heavy metals in tumor tissue. Conclusions: Heavy metals
      through different pathogenetic links stimulate the progression of breast cancer
      and reduce its sensitivity to treatment. DNA of tumor tissue has a different
      level of methylation which changes with the amount of heavy metals in cancer
      cells. This is displayed on the synthesis of prognostically important receptors
      in neoplastic tissue.

PMID- 29209408
TI  - Panicle-SEG: a robust image segmentation method for rice panicles in the field
      based on deep learning and superpixel optimization.
AB  - Background: Rice panicle phenotyping is important in rice breeding, and rice
      panicle segmentation is the first and key step for image-based panicle
      phenotyping. Because of the challenge of illumination differentials, panicle
      shape deformations, rice accession variations, different reproductive stages and
      the field's complex background, rice panicle segmentation in the field is a very
      large challenge. Results: In this paper, we propose a rice panicle segmentation
      algorithm called Panicle-SEG, which is based on simple linear iterative
      clustering superpixel regions generation, convolutional neural network
      classification and entropy rate superpixel optimization. To build the Panicle-SEG
      CNN model and test the segmentation effects, 684 training images and 48 testing
      images were randomly selected, respectively. Six indicators, including Qseg, Sr,
      SSIM, Precision, Recall and F-measure, are employed to evaluate the segmentation
      effects, and the average segmentation results for the 48 testing samples are
      0.626, 0.730, 0.891, 0.821, 0.730, and 76.73%, respectively. Compared with other
      segmentation approaches, including HSeg, i2 hysteresis thresholding and jointSeg,
      the proposed Panicle-SEG algorithm has better performance on segmentation
      accuracy. Meanwhile, the executing speed is also improved when combined with
      multithreading and CUDA parallel acceleration. Moreover, Panicle-SEG was
      demonstrated to be a robust segmentation algorithm, which can be expanded for
      different rice accessions, different field environments, different camera angles,
      different reproductive stages, and indoor rice images. The testing dataset and
      segmentation software are available online. Conclusions: In conclusion, the
      results demonstrate that Panicle-SEG is a robust method for panicle segmentation,
      and it creates a new opportunity for nondestructive yield estimation.

PMID- 29209409
TI  - Contrast-enhanced 3D micro-CT of plant tissues using different impregnation
      techniques.
AB  - Background: X-ray micro-CT has increasingly been used for 3D imaging of plant
      structures. At the micrometer resolution however, limitations in X-ray contrast
      often lead to datasets with poor qualitative and quantitative measures,
      especially within dense cell clusters of plant tissue specimens. The current
      study developed protocols for delivering a cesium based contrast enhancing
      solution to varying plant tissue specimens for the purpose of improving 3D tissue
      structure characterization within plant specimens, accompanied by new image
      processing workflows to extract the additional data generated by the contrast
      enhanced scans. Results: Following passive delivery of a 10% cesium iodide
      contrast solution, significant increases of 85.4 and 38.0% in analyzable cell
      volumes were observed in pear fruit hypanthium and tomato fruit outer mesocarp
      samples. A significant increase of 139.6% in the number of analyzable cells was
      observed in the pear fruit samples along the added ability to locate and isolate
      better brachysclereids and vasculature in the sample volume. Furthermore,
      contrast enhancement resulted in significant improvement in the definition of
      collenchyma and parenchyma in the petiolule of tomato leaflets, from which both
      qualitative and quantitative data can be extracted with respect to cell measures.
      However, contrast enhancement was not achieved in leaf vasculature and mesophyll
      tissue due to fundamental limitations. Active contrast delivery to apple fruit
      hypanthium samples did yield a small but insignificant increase in analyzable
      volume and cells, but data on vasculature can now be extracted better in
      correspondence to the pear hypanthium samples. Contrast delivery thus improved
      visualization and analysis the most in dense tissue types. Conclusions: The
      cesium based contrast enhancing protocols and workflows can be utilized to obtain
      detailed 3D data on the internal microstructure of plant samples, and can be
      adapted to additional samples of interest with minimal effort. The resulting
      datasets can therefore be utilized for more accurate downstream studies that
      requires 3D data.

PMID- 29209410
TI  - Public health implications of complex emergencies and natural disasters.
AB  - Background: During the last decade, conflict or natural disasters have displaced
      unprecedented numbers of persons. This leads to conditions prone to outbreaks
      that imperil the health of displaced persons and threaten global health security.
      Past literature has minimally examined the association of communicable disease
      outbreaks with complex emergencies (CEs) and natural disasters (NDs). Methods: To
      examine this association, we identified CEs and NDs using publicly available
      datasets from the Center for Research on the Epidemiology of Disasters and United
      Nations Flash and Consolidated Appeals archive for 2005-2014. We identified
      outbreaks from World Health Organization archives. We compared findings to
      identify overlap of outbreaks, including their types (whether or not of a vaccine
      preventable disease), and emergency event types (CE, ND, or Both) by country and
      year using descriptive statistics and measure of association. Results: There were
      167 CEs, 912 NDs, 118 events linked to 'Both' types of emergencies, and 384
      outbreaks. Of CEs, 43% were associated with an outbreak; 24% NDs were associated
      with an outbreak; and 36% of 'Both' types of emergencies were associated with an
      outbreak. Africa was disproportionately affected, where 67% of total CEs, 67% of
      'Both' events (CE and ND), and 46% of all outbreaks occurred for the study
      period. The odds ratio of a vaccine-preventable outbreak occurring in a CE versus
      an ND was 4.14 (95% confidence limits 1.9, 9.4). Conclusions: CEs had greater
      odds of being associated with outbreaks compared with NDs. Moreover, CEs had high
      odds of a vaccine-preventable disease causing that outbreak. Focusing on better
      vaccine coverage could reduce CE-associated morbidity and mortality by preventing
      outbreaks from spreading.

PMID- 29209411
TI  - Dietary behaviour, psychological well-being and mental distress among adolescents
      in Korea.
AB  - Background: Dietary intake is important for physical and mental health. The aim
      of this investigation was to assess associations between dietary behaviours and
      psychological well-being and distress among school-going adolescents in Korea.
      Methods: In a cross-sectional nationally representative survey, 65,212 students
      (Mean age = 15.1 years, SE = 0.02 and 52.2% male and 47.8% female) responded to a
      questionnaire that included measures of dietary behaviour, psychological well
      being and mental distress. Results: In logistic regression analyses, adjusted for
      age, sex, socioeconomic status, school level, school types, Body Mass Index,
      physical activity, and substance use, positive dietary behaviours (regular
      breakfast, fruit, vegetable, and milk consumption) were positively and unhealthy
      dietary behaviours (intake of caffeine, soft drinks, sweet drinks and fast food
      consumption) were negatively associated with self-reported health, happiness and
      sleep satisfaction. Positive dietary behaviours (regular breakfast, fruit,
      vegetable, and milk consumption) were negatively associated with perceived stress
      and depression symptoms. Unhealthy dietary behaviours (consumption of fast food,
      caffeine, sweetened drinks and soft drinks) were associated with perceived stress
      and depression symptoms. Conclusions: The study found strong cross-sectional
      evidence that healthy dietary behaviours were associated with lower mental
      distress and higher psychological well-being. It remains unclear, if a healthier
      dietary behaviour is the cause or the sequela of a more positive well-being.

PMID- 29209412
TI  - Minor physical anomalies in neurodevelopmental disorders: a twin study.
AB  - Background: Minor physical anomalies (MPAs) are subtle anatomical deviations in
      one's appearance and may suggest altered embryogenesis. MPAs have been shown to
      be more common in neurodevelopmental disorders (NDDs) compared with typical
      development. Still, further studies are needed on MPAs in NDDs, especially using
      twins to adjust for confounding familial factors. Methods: Clinical assessments
      were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7
      dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs.
      Additionally, the relationship between the number of MPAs within twins by
      zygosity was investigated. Results: Within the cohort sample, a specific
      association was found between MPAs and autism spectrum disorder (ASD) diagnosis
      (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26-1.33, adjusted p
      values = .032-.073) and autistic traits (crude beta = 3.02, p = .002; adjusted
      beta = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs.
      Identified MPAs in ASD included overweight, hypermobility, pes planus, straight
      eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and
      microtia. The number of MPAs within all monozygotic pairs was highly correlated
      (r = .88, p < .001). Conclusion: MPAs are more frequent in participants with ASD
      and may be influenced by genetics. The value of MPAs for (early) detection should
      be further explored, as they might index individuals at increased risk for ASD in
      particular.

PMID- 29209413
TI  - Examining changes in personality disorder and symptomology in an adolescent
      sample receiving intensive mentalization based treatment: a pilot study.
AB  - Objective: To examine changes in personality disorders and symptomology and the
      relation between personality disorder variables and treatment outcomes in an
      adolescent sample during partial residential mentalization based treatment.
      Methods: In a sample of 62 (out of 115) adolescents treated for personality
      disorders, assessment was done pre- and post-treatment using the Structured
      Clinical Interview for DSM personality disorders and the Symptom Check List 90.
      Results: Significant reductions in personality disorder traits (t = 8.36, p =
      .000) and symptoms (t = 5.95, p = .000) were found. During pre-treatment, 91.8%
      (n = 56) of the patients had one or more personality disorders, compared to 35.4%
      (n = 22) at post-treatment. Symptom reduction was not related to pre-treatment
      personality disorder variables. Conclusion: During intensive psychotherapy,
      personality disorders and symptoms may diminish. Future studies should evaluate
      whether the outcomes obtained are the result of the treatment given or other
      factors.

PMID- 29209415
TI  - Undefined cellulase formulations hinder scientific reproducibility.
AB  - In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of
      lignocellulose to fermentable sugars in a cost-effective manner is key to the
      success of second-generation and advanced biofuel production. For the effective
      comparison of one cellulase preparation to another, cellulase assays are
      typically carried out with one or more engineered cellulase formulations or
      natural exoproteomes of known performance serving as positive controls. When
      these formulations have unknown composition, as is the case with several widely
      used commercial products, it becomes impossible to compare or reproduce work done
      today to work done in the future, where, for example, such preparations may not
      be available. Therefore, being a critical tenet of science publishing,
      experimental reproducibility is endangered by the continued use of these
      undisclosed products. We propose the introduction of standard procedures and
      materials to produce specific and reproducible cellulase formulations. These
      formulations are to serve as yardsticks to measure improvements and performance
      of new cellulase formulations.

PMID- 29209416
TI  - Reliability of analysis of the bone mineral density of the second and fifth
      metatarsals using dual-energy x-ray absorptiometry (DXA).
AB  - Background: Metatarsal fractures, especially of the fifth metatarsal, are common
      injuries of the foot in a young athletic population, but the risk factors for
      this injury are not well understood. Dual-energy x-ray absorptiometry (DXA)
      provides reliable measures of regional bone mineral density to predict fracture
      risk in the hip and lumbar spine. Recently, sub-regional metatarsal reliability
      was established in fresh cadaveric specimens and associated with ultimate
      fracture force. The purpose of this study was to assess the reliability of DXA
      bone mineral density measurements of sub-regions of the second and fifth
      metatarsals in a young, active population. Methods: Thirty two recreationally
      active individuals participated in the study, and the bone density of the second
      (2MT) and fifth (5MT) metatarsals of each subject was measured using a Hologic
      QDR x-ray bone densitometer. Scans were analyzed separately by two raters, and
      regional bone mineral density, bone mineral content, and area measurements were
      calculated for the proximal, shaft, and distal regions of the bone. Intra-rater,
      inter-rater, and scan-rescan reliability were then determined for each region.
      Results: Proximal and shaft bone mineral density measurements of the second and
      fifth metatarsal were reliable. ICC's were variable across regions and
      metatarsals, with the distal region being the poorest. Conclusions: Bone mineral
      density measurements of the metatarsals may be a better indicator of fracture
      risk of the metatarsals than whole body measurements. A reliable method for
      measuring the regional bone mineral densities of the metatarsals was found.
      However, inter-rater reliability and scan-rescan reliability for the distal
      regions were poor. Future research should examine the relationship between DXA
      bone mineral density measurements and fracture risk at the metatarsals.

PMID- 29209414
TI  - Quantitative in vivo phosphoproteomics reveals reversible signaling processes
      during nitrogen starvation and recovery in the biofuel model organism
      Chlamydomonas reinhardtii.
AB  - Background: Nitrogen deprivation and replenishment induces massive changes at the
      physiological and molecular level in the green alga Chlamydomonas reinhardtii,
      including reversible starch and lipid accumulation. Stress signal perception and
      acclimation involves transient protein phosphorylation. This study aims to
      provide the first experimental phosphoprotein dataset for the adaptation of C.
      reinhardtii during nitrogen depletion and recovery growth phases and its impact
      on lipid accumulation. Results: To decipher the signaling pathways involved in
      this dynamic process, we applied a label-free in vivo shotgun phosphoproteomics
      analysis on nitrogen-depleted and recovered samples. 1227 phosphopeptides
      belonging to 732 phosphoproteins were identified and quantified. 470
      phosphopeptides showed a significant change across the experimental set-up.
      Multivariate statistics revealed the reversible phosphorylation process and the
      time/condition-dependent dynamic rearrangement of the phosphoproteome. Protein
      protein interaction analysis of differentially regulated phosphoproteins
      identified protein kinases and phosphatases, such as DYRKP and an AtGRIK1
      orthologue, called CDPKK2, as central players in the coordination of
      translational, photosynthetic, proteomic and metabolomic activity.
      Phosphorylation of RPS6, ATG13, and NNK1 proteins points toward a specific
      regulation of the TOR pathway under nitrogen deprivation. Differential
      phosphorylation pattern of several eukaryotic initiation factor proteins (EIF)
      suggests a major control on protein translation and turnover. Conclusion: This
      work provides the first phosphoproteomics dataset obtained for Chlamydomonas
      responses to nitrogen availability, revealing multifactorial signaling pathways
      and their regulatory function for biofuel production. The reproducibility of the
      experimental set-up allows direct comparison with proteomics and metabolomics
      datasets and refines therefore the current model of Chlamydomonas acclimation to
      various nitrogen levels. Integration of physiological, proteomics, metabolomics,
      and phosphoproteomics data reveals three phases of acclimation to N availability:
      (i) a rapid response triggering starch accumulation as well as energy metabolism
      while chloroplast structure is conserved followed by (ii) chloroplast degradation
      combined with cell autophagy and lipid accumulation and finally (iii) chloroplast
      regeneration and cell growth activation after nitrogen replenishment. Plastid
      development seems to be further interconnected with primary metabolism and energy
      stress signaling in order to coordinate cellular mechanism to nitrogen
      availability stress.

PMID- 29209419
TI  - Breathe: palliative care in respiratory medicine.
AB  - The December issue of Breathe focuses on palliative care in respiratory disease
      http://ow.ly/LN5130fTQus.

PMID- 29209417
TI  - Do athletes alter their running mechanics after an Achilles tendon rupture?
AB  - Background: Over the past thirty years, there has been dramatic increase in
      incidence of Achilles tendon rupture in the athletic population. The purpose of
      this study was to compare the lower extremity mechanics of Achilles tendon
      ruptured runners with healthy controls. Methods: The participants with a past
      history of an Achilles tendon repair (n = 11) and healthy control (n = 11)
      subgroups were matched on sex, age, type of regular physical activity, mass,
      height, footfall pattern and lateral dominancy. Running kinetics and kinematics
      of the ankle, knee and hip were recorded using a high-speed motion capture system
      interfaced with a force platform. Achilles tendon length was measured using
      ultrasonography. Main outcome measures were lower extremity joint angles and
      moments during stance phase of running and Achilles tendon lengths. Results:
      Athletes from Achilles tendon group had an affected gastro-soleus complex.
      Athletes with history of Achilles tendon rupture had reduced ankle range of
      motion during second half of the stance phase of running (Delta7.6 degrees ), an
      overextended knee during initial contact (Delta5.2 degrees ) and increased
      affected knee range of motion (Delta4.4 degrees ) during the first half of stance
      phase on their affected limb compared to the healthy control group. There was a
      22% increase in the maximal hip joint moment on contralateral side of the
      Achilles tendon group compared to the healthy controls. Conclusion: These results
      suggest a compensation mechanism, relatively extended knee at initial ground
      contact against the deficit in the muscle-tendon complex of the triceps surae.
      Overextension during sporting activities may place the knee at risk for further
      injury. Avoidance of AT lengthening and plantarflexion strength deficit after
      surgery and during rehabilitation might help to manage AT rupture since these
      factors may be responsible for altered running kinematics.

PMID- 29209421
TI  - Pulmonary rehabilitation: ?course report.
AB  - Delegates of an @ERStalk course on pulmonary rehabilitation describe their
      experiences http://ow.ly/VVp030fGC1x.

PMID- 29209420
TI  - Progressive respiratory disease: the importance of prognostic conversations and
      advance care planning.
AB  - Prognostic conversations and advance care planning facilitate improved care in
      life-limiting respiratory conditions http://ow.ly/MOtp30fqPOw.

PMID- 29209422
TI  - The potential of palliative care for patients with respiratory diseases.
AB  - : Based on the demonstrated effectiveness of palliative care in the alleviation
      of symptoms and enhancement of life quality, it is important to incorporate
      palliative care early in the respiratory disease trajectory. Quality palliative
      care addresses eight domains that are all patient and family centred. Palliative
      care interventions in respiratory conditions include management of symptoms such
      as dyspnoea, cough, haemoptysis, sputum production, fatigue and respiratory
      secretion management, especially as the end-of-life nears. A practical checklist
      of activities based on the domains of palliative care can assist clinicians to
      integrate palliative care into their practice. Clinical management of patients
      receiving palliative care requires consideration of human factors and related
      organisational characteristics that involve cultural, educational and
      motivational aspects of the patient/family and clinicians. Educational aims: To
      explain the basic domains of palliative care applicable to chronic respiratory
      diseases.To review palliative care interventions for patients with chronic
      respiratory diseases.To outline a checklist for clinicians to use in practice,
      based on the domains of palliative care.To propose recommendations for clinical
      management of patients receiving palliative care for chronic respiratory
      diseases.

PMID- 29209424
TI  - Severe COPD and the transition to a palliative approach.
AB  - : Patients with severe chronic obstructive pulmonary disease (COPD) have a
      chaotic trajectory towards death. Research has focused on identifying a
      "transition point" that would allow identification of those patients who may
      benefit from a palliative approach to their care, or referral to a specialist
      palliative care service. This article aims to outline difficulties in identifying
      this transition point, summarise current literature on this topic and suggests a
      model based on clinical milestones. Educational aims: To outline the difficulties
      associated with identifying patients with severe COPD who are at risk of dying.To
      summarise current research on this topic. Key points: A specific transition point
      is difficult to identify in severe COPD.Tools are available that may assist the
      physician in identifying those at risk of dying.It is essential that the patient
      voice is heard, patients can describe specific events that may be used as a
      "trigger" for a palliative approach.Specialist palliative care services may only
      be required for a subgroup of patients whose needs cannot be managed by the
      primary care team.

PMID- 29209423
TI  - The physiological effects of slow breathing in the healthy human.
AB  - : Slow breathing practices have been adopted in the modern world across the globe
      due to their claimed health benefits. This has piqued the interest of researchers
      and clinicians who have initiated investigations into the physiological (and
      psychological) effects of slow breathing techniques and attempted to uncover the
      underlying mechanisms. The aim of this article is to provide a comprehensive
      overview of normal respiratory physiology and the documented physiological
      effects of slow breathing techniques according to research in healthy humans. The
      review focuses on the physiological implications to the respiratory,
      cardiovascular, cardiorespiratory and autonomic nervous systems, with particular
      focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate
      variability, cardiorespiratory coupling, respiratory sinus arrhythmia and
      sympathovagal balance. The review ends with a brief discussion of the potential
      clinical implications of slow breathing techniques. This is a topic that warrants
      further research, understanding and discussion. Key points: Slow breathing
      practices have gained popularity in the western world due to their claimed health
      benefits, yet remain relatively untouched by the medical community.Investigations
      into the physiological effects of slow breathing have uncovered significant
      effects on the respiratory, cardiovascular, cardiorespiratory and autonomic
      nervous systems.Key findings include effects on respiratory muscle activity,
      ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate
      variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory
      coupling, and sympathovagal balance.There appears to be potential for use of
      controlled slow breathing techniques as a means of optimising physiological
      parameters that appear to be associated with health and longevity, and that may
      extend to disease states; however, there is a dire need for further research into
      the area. Educational aims: To provide a comprehensive overview of normal human
      respiratory physiology and the documented effects of slow breathing in healthy
      humans.To review and discuss the evidence and hypotheses regarding the mechanisms
      underlying slow breathing physiological effects in humans.To provide a definition
      of slow breathing and what may constitute "autonomically optimised
      respiration".To open discussion on the potential clinical implications of slow
      breathing techniques and the need for further research.

PMID- 29209425
TI  - Bilateral pulmonary nodules and acute respiratory failure in a 22-year-old man
      with dyspnoea and fever.
AB  - Can you diagnose the cause of this man's bilateral pulmonary nodules and acute
      respiratory failure? http://ow.ly/NfED30dDBzm.

PMID- 29209426
TI  - Early Career Members at the ERS LSC 2017: mechanistic overlap between chronic
      lung injury and cancer.
AB  - .@EarlyCareerERS looks back on #LSC2017 http://ow.ly/I3M730fkn5X.

PMID- 29209427
TI  - How to give and receive ?feedback effectively.
AB  - Giving and receiving effective feedback are skills that are central in healthcare
      settings http://ow.ly/zZ1C30eVrH1.

PMID- 29209428
TI  - Radiology corner.

PMID- 29209429
TI  - Confidences de Salon: Andy Bush.
AB  - ERS Publications Chair, Andy Bush, gives an insight into his
      lifehttp://ow.ly/hkQ830fQJHU.

PMID- 29209430
TI  - Mould, damp and the lungs.
AB  - Mould is a type of fungus that grows in damp areas. It releases tiny particles
      called spores that can be harmful when breathed in.

PMID- 29209431
TI  - Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia
      improves prognosis prediction for patients with isolated 13q deletion.
AB  - Background: Both defective DNA methylation and active DNA demethylation processes
      are emerging as important risk factors in chronic lymphocytic leukemia (CLL).
      However, associations between 5-cytosine epigenetic markers and the most frequent
      chromosomal abnormalities detected in CLL remain to be established. Methods: CLL
      patients were retrospectively classified into a cytogenetic low-risk group
      (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy
      12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [>=
      3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5
      hydroxymethylcytosine (5-hmCyt), were tested by ELISA (n = 60), while real-time
      quantitative PCR was used for determining transcriptional expression levels of
      DNMT and TET (n = 24). Results: By using global DNA methylation/demethylation
      levels, in the low-risk disease group, two subgroups with significantly different
      clinical outcomes have been identified (median treatment-free survival [TFS] 45
      versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5
      hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher
      percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process.
      When considering the cytogenetic intermediate/high-risk disease groups, an
      association of 5-mCyt status with lymphocytosis (p = 0.0008) and the lymphocyte
      doubling time (p = 0.04) but not with TFS was observed, as well as a reduction of
      DNMT3A, TET1, and TET2 transcripts. Conclusions: Combining cytogenetic studies
      with 5-mCyt assessment adds accuracy to CLL patients' prognoses and particularly
      for those with 13q deletion as a sole cytogenetic abnormality.

PMID- 29209432
TI  - Epigenetic modifications of the VGF gene in human non-small cell lung cancer
      tissues pave the way towards enhanced expression.
AB  - Hwang et al. recently showed that VGF substantially contributes to the resistance
      of human lung cancer cells towards epidermal growth factor receptor kinase
      inhibitors. This was further linked to enhanced epithelial-mesenchymal
      transition. Here, we demonstrate that VGF is epigenetically modified in non-small
      cell lung cancer tissues compared to corresponding tumor-free lung tissues from
      the same donors by using methylome bead chip analyses. These epigenetic
      modifications trigger an increased transcription of the VGF gene within the
      tumors, which then leads to an increased expression of the protein, facilitating
      epithelial-mesenchymal transition, and the resistance to kinase inhibitors. These
      results should be taken into account in the design of novel therapeutic and
      diagnostic approaches.

PMID- 29209435
TI  - Diseases potentially related to Flammer syndrome.
AB  - Flammer syndrome (FS) is a prevalent and mostly benign condition. Subjects with
      FS seem to have a good life expectancy. Nevertheless, FS subjects are at
      increased risk for certain diseases, mainly when they are challenged by
      psychological stress or other stimuli such as coldness. FS is related to ocular
      diseases, such as normal-tension glaucoma, retinitis pigmentosa, central serous
      chorioretinopathy, optic nerve compartment syndrome, Leber's hereditary optic
      neuropathy, arterial or venous occlusions in the retina, and choroid and optic
      nerve head, despite the absence of classical vascular risk factors. FS is also
      related to some non-ocular diseases, such as multiple sclerosis, breast cancer,
      and altitude sickness. The role of FS in other diseases such as tinnitus, sudden
      hearing loss, Meniere's disease, anorexia nervosa, and thyroid dysfunction is
      currently under investigation. The exact relationship of FS to related diseases
      however still needs to be established. This may hopefully lead to more targeted
      diagnostics and personalized treatments.

PMID- 29209433
TI  - Novel insights into epigenetic drivers of oropharyngeal squamous cell carcinoma:
      role of HPV and lifestyle factors.
AB  - In the last years, the explosion of high throughput sequencing technologies has
      enabled epigenome-wide analyses, allowing a more comprehensive overview of the
      oropharyngeal squamous cell carcinoma (OPSCC) epigenetic landscape. In this
      setting, the cellular pathways contributing to the neoplastic phenotype,
      including cell cycle regulation, cell signaling, DNA repair, and apoptosis have
      been demonstrated to be potential targets of epigenetic alterations in OPSCC. Of
      note, it has becoming increasingly clear that HPV infection and OPSCC lifestyle
      risk factors differently drive the epigenetic machinery in cancer cells.
      Epigenetic changes, including DNA methylation, histone modifications, and non
      coding RNA expression, can be used as powerful and reliable tools for early
      diagnosis of OPSCC patients and improve prognostication. Since epigenetic changes
      are dynamic and reversible, epigenetic enzymes may also represent suitable
      targets for the development of more effective OPSCC therapeutic strategies. Thus,
      this review will focus on the main known epigenetic modifications that can occur
      in OPSCC and their exploitation as potential biomarkers and therapeutic targets.
      Furthermore, we will address epigenetic alterations to OPSCC risk factors, with a
      particular focus on HPV infection, tobacco exposure, and heavy alcohol
      consumption.

PMID- 29209436
TI  - The potential relationship between Flammer and Sjogren syndromes: the chime of
      dysfunction.
AB  - Flammer syndrome (FS) is a term to blanket a cluster of vascular and nonvascular
      signs and symptoms linked to primary vascular dysregulation (PVD), increased
      sensitivity to various stimuli (stress, drugs, etc.) and altered sense regulation
      such as pain, smell and thirst perception. On one hand, disruption of blood
      barrier and homeostasis of the body are the main targets of vascular
      irregularity. Inflammation and immune disorders including autoimmunity are
      considered as a consequence of the abnormal vascular regulation processes. On the
      other hand, decreased thirst feeling typical for FS-affected individuals may lead
      to extensive body dehydration resulting in dry eye appearance and breast cancer
      (BC) risk, amongst others. To this end, recent research demonstrated FS as linked
      to BC development and progression into the metastatic disease. On the other side,
      Sjogren syndrome (SS) is an autoimmune disease characterised by a progressive
      sicca syndrome associated with the dry eye symptoms, specific immunologic complex
      and/or significant infiltrate at minor salivary gland biopsy. SS is relatively
      frequent, with a clinical diagnosis predominantly amongst women. Its
      physiopathology is a complex battery of both environmental and genetic factors.
      If left untreated, SS may be associated with and/or resulted in severe arthritis
      and the development of B cell lymphoma. In this mini-review, we summarise the
      facts and hypotheses connecting FS and SS symptoms together and mechanisms
      potentially overlapping in both syndromes. Unraveling the common denominators
      between these two syndromes not only providing more evidence for interaction
      between altered sense regulation, vascular dysregulation, immune system
      dysfunction but also focusing on the individual outcomes in terms of severity
      grade and potential complications exploring novel diagnostic, prognostic and
      treatment modalities. Multi-professional considerations presented here are an
      example how to effectively enter the new era of preventive, predictive and
      personalised medicine benefiting the patients and healthcare system as the whole.

PMID- 29209434
TI  - Vitamin D in the prevention, prediction and treatment of neurodegenerative and
      neuroinflammatory diseases.
AB  - Vitamin D research has gained increased attention in recent times due to its
      roles beyond bone health and calcium homeostasis, such as immunomodulation. In
      some parts of the brain and on immune cells, vitamin D hydroxylating enzymes and
      its receptors are located. Epidemiological evidence demonstrates that deficiency
      of Vitamin D is relevant for disease risk and course in multiple sclerosis (MS)
      and presumably also in neuromyelitis optica spectrum disorders (NMOSD),
      Parkinson's disease (PD), and Alzheimer's disease (AD). Although the exact
      mechanism underlying vitamin D effects in these diseases remains widely
      unexplored, human and animal studies continue to provide some hints. While the
      majority of vitamin D researchers so far speculate that vitamin D may be involved
      in disease pathogenesis, others could not show any association although none have
      reported that sufficient vitamin D worsens disease progression. The studies
      presented in this review suggest that whether vitamin D may have beneficial
      effects in disease course or not, may be dependent on factors such as ethnicity,
      gender, diet, vitamin D receptor (VDR) polymorphisms and sunlight exposure. We
      here review the possible role of vitamin D in the pathogenesis and disease course
      of MS, NMOSD, PD, and AD and potential therapeutic effects of vitamin D
      supplementation which may be relevant for predictive, preventive, and
      personalized medicine. We suggest areas to consider in vitamin D research for
      future studies and recommend the need to supplement patients with low vitamin D
      levels below 30 ng/ml to at least reach sufficient levels.

PMID- 29209437
TI  - Retinal venous pressure measurements in patients with Flammer syndrome and
      metabolic syndrome.
AB  - Background: The purpose of this research is to analyze retinal venous pressure
      (RVP) of both eyes of patients who visited a Swiss ophthalmic practice and
      compare values among the following groups of patients with primary open-angle
      glaucoma (POAG), Flammer syndrome (FS), and metabolic syndrome (MetS). Methods:
      RVP was measured in both eyes of all patients who visited a Swiss ophthalmic
      practice during March 2016 till November 2016, and the results were analyzed
      retrospectively. All measurements were performed by one physician by means of
      ophthalmodynamometry. Ophthalmodynamometry is done by applying an increasing
      pressure on the eye via a contact lens. The minimum force required to induce a
      venous pulsation is called ophthalmodynamometric force (ODF). The RVP is defined
      and calculated as the sum of ODF and intraocular pressure (IOP) [RVP = ODF +
      IOP]. Results: Spontaneous central retinal venous pulsation was present in the
      majority of the patients (192 out of 357, 53.8%). Spontaneous RVP rate was
      significantly negatively correlated with age (r = -0.348, p < 0.001). A
      significantly increased RVP was noted in FS, MetS, and POAG patients,
      particularly those POAG patients who also suffered from FS (p < 0.005).
      Conclusions: Although most patients had a spontaneous RVP, those with FS, POAG,
      and MetS had increased RVP. Measuring RVP by means of ophthalmodynamometry
      provides predictive information about certain ocular diseases and aids in
      instituting adequate preventive measures.

PMID- 29209438
TI  - Incorporation of suboptimal health status as a potential risk assessment for type
      II diabetes mellitus: a case-control study in a Ghanaian population.
AB  - Due to a paradigm shift in lifestyles, there is growing concern that type 2
      diabetes mellitus (T2DM) will reach epidemic proportions in Ghana. However,
      specific characteristics of the disease are under explored in this region. More
      challenging are those yet to be diagnosed or who complain of poor health in the
      absence of a diagnosed disease-suboptimal health status (SHS). We conducted a
      study to examine various factors that characterise SHS and T2DM. Using a cross
      sectional design, we recruited 264 people as controls and 241 T2DM patients from
      January to June 2016. The controls were categorised into high and low SHS based
      on how they rated on an SHS questionnaire-25 (SHSQ-25). Anthropometric and
      biochemical parameters: body mass index (BMI); blood pressure (BP); fasting
      plasma glucose (FPG); glycated haemoglobin (HbA1c); serum lipids [(total
      cholesterol, triglycerides (TG), high- and low-density lipoprotein-cholesterol
      (HDL-c and LDL-c)] were measured. The male to female ratio for T2DM and controls
      were 99:142 and 98:166, respectively, whilst the mean ages were 55.89 and 51.52
      years. Compared to controls, T2DM patients had higher FPG (8.96 +/- 4.18 vs. 6.08
      +/- 1.79; p < 0.0001) and HbA1c (8.23 +/- 2.09 vs. 5.45 +/- 1.00; p < 0.0001).
      Primarily sedentary [adjusted odds ratio (aOR) = 2.97 (1.38-6.39); p = 0.034)],
      systolic blood pressure (SBP) (p = 0.001) and diastolic blood pressure (DBP) (p =
      0.001) significantly correlated with high SHS. After adjusting for age and
      gender, central adiposity [aOR = 1.74 (1.06-2.83); p = 0.027)], underweight [aOR
      = 5.82 (1.23-27.52); p = 0.018)], high SBP [aOR = 1.86 (1.14-3.05); p = 0.012)],
      high DBP [aOR = 2.39 (1.40-4.07); p = 0.001)] and high TG [aOR = 2.17 (1.09
      4.33); p = 0.029)] were found to be independent risk factors associated with high
      SHS. The management of T2DM in Ghana is suboptimal and undiagnosed risk factors
      remain prevalent. The SHSQ-25 can be translated and applied as a practical tool
      to screen at-risk individuals and hence prove useful for the purpose of
      predictive, preventive and personalised medicine.

PMID- 29209439
TI  - Comparative study of probiotic effects of Lactobacillus and Bifidobacteria
      strains on cholesterol levels, liver morphology and the gut microbiota in obese
      mice.
AB  - Background: Microbiome-modulating interventions are promising for treatment and
      prevention of metabolic syndrome. The number of probiotic strains demonstrated
      ability to decrease cholesterol level in vivo, however, it was poorly confirmed
      in a clinical setting. The aim was to study the effects of L. acidophilus IMV B
      7279, L. casei IMV B-7280, B. animalis VKL and B. animalis VKB separately and in
      various compositions on the level of serum cholesterol, gut microbiota contents
      and liver morphology on a high-calorie-induced obesity model in BALB/c mice.
      Materials and methods: We used for the study female BALB/c mice 6-8 weeks old (18
      24 g). Experimental animals were fed by a fat-enriched diet (FED), and 8
      experimental groups were formed (12 mice in each group) to test strains of
      probiotic bacteria L. delbrueckii subsp. bulgaricus IMV B-7281, L. casei IMV B
      7280, B. animalis VKL and B. animalis VKB and compositions. We used ultrasound
      for in vivo assessment of the liver and visceral (mesenteric) fat size. In the
      blood serum of the obese mice, the level of cholesterol was estimated. The liver
      morphology and gut microbiota of obese mice were studied. Results: We revealed
      that after treatment with all of the studied probiotic bacteria and compositions
      of B. animalis VKL/B. animalis VKB/L. casei IMV B-7280, the weight of obese mice
      decreased, and cholesterol and its fraction levels in serum were reduced. The
      size of the liver slightly decreased after treatment with L. delbrueckii subsp.
      bulgaricus IMV B-7281, B. animalis VKB or probiotic compositions; we observed
      reduction of the mesenteric fat size after injection of all these probiotic
      bacteria (separately) and probiotic compositions. We defined the strain-dependent
      effects on serum lipid profiles, liver morphology and the gut microbiota. The B.
      animalis VKL/B. animalis VKB/L. casei IMV B-7280 composition effectively
      recovered the liver morphological structure of obese mice. The number of
      Lactobacillus spp., Bifidobacterium spp. and coliform bacteria increased, the
      number of staphylococci and streptococci reduced, and the number of microscopic
      fungi significantly decreased in the gut of obese mice after treatment with L.
      casei IMV B-7280, L. delbrueckii subsp. bulgaricus IMV B-7281, B. animalis
      (separately) or their compositions. Conclusion: L. casei IMV B-7280 (separately)
      and a composition of B. animalis VKL/B. animalis VKB/L. casei IMV B-7280 are
      effective at decreasing the weight of obese mice, decreasing cholesterol level,
      restoring the liver morphology and beneficially modulating the gut microbiome in
      high-calorie-induced obesity.

PMID- 29209442
TI  - Getting to Phase 3: an Interview with Virginia S. Cowen, PhD, LMT.
AB  - I feel that it is important to know the stories behind those who are working hard
      in the field to bring forward massage therapy research. Interviews with massage
      therapy researchers will now occasionally be included in the Journal as a new
      editorial feature. The first interview is with Virginia S. Cowen, PhD, LMT a New
      York State-licensed and NCB board-certified massage therapist with a PhD from
      Arizona State. She first became interested in massage therapy research while in
      massage therapy school, and her most recent work is investigating the integration
      of massage therapy into medical settings. Dr. Cowen states that massage therapy
      needs to move to Phase 3 research, and aligning with massage therapy practice and
      research on massage therapy education are areas ripe for research development.
      She urges the massage therapy profession to work together to develop clinical
      practice guidelines which could help move the profession forward.

PMID- 29209440
TI  - Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous
      intoxication in high-calorie diet-induced obesity rat model-comparative study.
AB  - Background: Worldwide obesity spread is a global health problem and needs to be
      further studied. Co-morbidities of obesity include insulin resistance, diabetes
      mellitus type 2, and dyslipidemia, which are the most frequent contributing
      factors for metabolic syndrome (MetS), as well as non-alcoholic fatty liver
      disease and chronic kidney disease. The aim was to study renal function and
      endogenous intoxication panel on high-calorie diet-induced obesity rat model and
      perform comparative study of the treatment efficacy of Fenugreek-based
      bionanocomposite vs antiobesogenic drugs (Orlistat). Materials: We included 60
      male rats and equally divided them to 6 groups of 10 animals in each group: the
      experimental groups were firstly assigned as controls and high caloric diet (HCD)
      fed groups, and each group further was subdivided to remain untreated, Fenugreek
      bionanocomposite (BNC)-treated, and Orlistat-treated. Normal control rats (groups
      1, 2, 3) were fed by a standard chow, while the others (groups 4, 5, 6) were fed
      with HCD ad libitum during 98 days. From days 77 to 98, groups 2 and 5 were
      treated with BNC based on Fenugreek (150 mg/kg body weight, orally) and groups 3
      and 6 were treated with antiobesogenic drug Orlistat (10 mg/kg body weight,
      orally). Food and water consumptions were measured daily and body weights were
      measured once a week. On day 99, blood was collected; the creatinine, urea, and
      uric acid were estimated in serum according to the standard protocols. Levels of
      low and middle molecules (MMs) were measured; the quantity of oligopeptides was
      estimated by Bradford method. We performed the liver and kidney ultrasonography
      in rats. Results: We revealed an increase in the levels of endogenous
      intoxication syndrome markers (MM and oligopeptides) in all animals with
      experimental obesity. Ultrasound data showed injury of the liver and kidneys in
      obese rats. We observed significant decreasing of MM levels after Orlistat
      treatment vs controls (p < 0.05). However, this effect was more pronounced in
      Fenugreek BNC-treated group vs both Orlistat-treated and controls (p < 0.05).
      Orlistat treatment evoked rising of serum creatinine and oligopeptides in control
      animals and failed to normalize these markers in experimental group. Fenugreek
      based BNC treatment did not evoke signs of kidney failure and changes in the
      studied indices in control group. We noticed normalization levels of uric acid
      and urea in the blood under the use of BNC and Orlistat. Conclusion: High-calorie
      diet-induced obesity evokes endogenous intoxication syndrome and kidney
      dysfunction in rats. Application of Orlistat- and Fenugreek-based BNC decreases
      MM content to the normal level. Orlistat induces increasing levels of
      oligopeptides in both groups, likely due to adverse side effects on renal
      function and its pro-oxidant activity.

PMID- 29209443
TI  - Incentivizing Peer Review.
AB  - Since the 1700s, peer review has been a part of scientific publication. Quality
      peer reviews take extensive time and effort yet reviewers are not often
      compensated. This editorial announces the new offering of the National
      Certification Board for Thereputic Massage & Bodywork (NCBTMB)-approved
      continuing education hours for our peer reviewers who complete timely reviews.
      Instructions to register as a peer reviewer and how to conduct a review are
      offered. Thank you to our 2016 and 2017 peer reviewers.

PMID- 29209441
TI  - PCSK9 signaling pathways and their potential importance in clinical practice.
AB  - In the following review, authors described the structure and biochemical pathways
      of PCSK9, its involvement in LDL metabolism, as well as significances of
      proprotein convertase subtilisin/kexin type 9 targeted treatment. PCSK9 is a
      proprotein convertase, which plays a crucial role in LDL receptor metabolism.
      Transcription and translation of PCSK9 is controlled by different nuclear
      factors, such as, SREBP and HNF1alpha. This review focuses on interactions
      between PCSK9 and LDL receptor, VLDLR, ApoER2, CD36, CD81, and others. The role
      of PCSK9 in the inflammatory process is presented and its influence on cytokine
      profile (IL-1, IL-6, IL-10, TNF) in atherosclerotic plaque. Cholesterol
      metabolism converges also with diabetes by mTORC1 pathways. PCSK9 can be altered
      by oncologic pathways with utilization of kinases, such as Akt, JNK, and
      JAK/STAT. Finally, the article shows that blocking PCSK9 has proapoptotic
      capabilities. Administration of monoclonal antibodies against PCSK9 reduced
      mortality rate and cardiovascular events in randomized trials. On the other hand,
      immunogenicity of new drugs may play a crucial role in their efficiency.
      Bococizumab ended its career following SPIRE-1,2 outcome. PCSK9 inhibitors have
      enormous potential, which had been reflected by introducing them (as a new class
      of drugs reducing LDL concentration cholesterol) into New Lipid Guidelines from
      Rome 2016. Discoveries in drugs development are focused on blocking PCSK9 on
      different levels. For example, silencing messenger RNA (mRNA of PCSK9) is a new
      alternative against hypercholesterolemia. Peptides mimicking EGF-A domain of the
      LDL receptor are gaining significance and hopefully they will soon join others.
      The significance of PCSK9 has just been uncovered and further data is still
      required to understand their activity.

PMID- 29209444
TI  - A Commentary on the Role of Randomized Controlled Trials in Massage Therapy.

PMID- 29209445
TI  - Recent Advances on In Situ SEM Mechanical and Electrical Characterization of Low
      Dimensional Nanomaterials.
AB  - In the past decades, in situ scanning electron microscopy (SEM) has become a
      powerful technique for the experimental study of low-dimensional (1D/2D)
      nanomaterials, since it can provide unprecedented details for individual
      nanostructures upon mechanical and electrical stimulus and thus uncover the
      fundamental deformation and failure mechanisms for their device applications. In
      this overview, we summarized recent developments on in situ SEM-based mechanical
      and electrical characterization techniques including tensile, compression,
      bending, and electrical property probing on individual nanostructures, as well as
      the state-of-the-art electromechanical coupling analysis. In addition, the
      advantages and disadvantages of in situ SEM tests were also discussed with some
      possible solutions to address the challenges. Furthermore, critical challenges
      were also discussed for the development and design of robust in situ SEM
      characterization platform with higher resolution and wider range of samples.
      These experimental efforts have offered in-depth understanding on the mechanical
      and electrical properties of low-dimensional nanomaterial components and given
      guidelines for their further structural and functional applications.

PMID- 29209446
TI  - Oxidative Stress Alters the Profile of Transcription Factors Related to Early
      Development on In Vitro Produced Embryos.
AB  - High oxygen levels during in vitro culture (IVC) can induce oxidative stress
      through accumulation of reactive oxygen species (ROS), negatively affecting
      embryo development. This study evaluated the effect of different O2 tensions
      during IVC on bovine blastocyst development and transcriptional status,
      considering transcription factors that play an essential role during early embryo
      development. For this purpose, embryos were produced in vitro by conventional
      protocols and cultured in two different oxygen tensions, physiological (5%) and
      atmospheric (20%). Expanded blastocysts were subjected to transcript quantitation
      analysis by RT-qPCR with BiomarkTM HD System (Fluidigm, US), using 67 TaqMan
      assays specific for Bos taurus. Differences were observed in genes related to
      oxidation-reduction processes, DNA-dependent transcription factors, and factors
      related to important functional pathways for embryo development. Blastocyst rate
      was higher in the 5% O2 group and the number of cells was assessed, with the 5%
      O2 group having a higher number of cells. ROS concentration was evaluated, with a
      higher ROS presence in the 20% O2 group. Taken together, these results allow us
      to conclude that IVC of embryos at atmospheric O2 tension affects the expression
      of important transcription factors involved in multiple cell biology pathways
      that can affect embryo development, quality, and viability.

PMID- 29209447
TI  - Nrf2, a Potential Therapeutic Target against Oxidative Stress in Corneal
      Diseases.
AB  - Corneal diseases are one of the major causes of blindness worldwide. Conservative
      medical agents, which may prevent sight-threatening corneal disease progression,
      are urgently desired. Numerous evidences have revealed the involvement of
      oxidative stress in various corneal diseases, such as corneal wound healing and
      Fuchs endothelial corneal dystrophy (FECD). Nuclear factor (erythroid-derived 2)
      like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology- (ECH-)
      associated protein 1 (Keap1)/antioxidant response element (ARE) signaling is well
      known as one of the main antioxidative defense systems. To the best of our
      knowledge, this is the first review to elucidate the different expression
      profiles of Nrf2 signaling as well as the underlying mechanisms in corneal
      diseases, implicating that Nrf2 may serve as a potentially promising therapeutic
      target for corneal diseases.

PMID- 29209449
TI  - Effect of oleanolic acid on small intestine morphology and enzymes of glutamine
      metabolism in diabetic rats.
AB  - The small intestine (SI) is the main site for food absorption and glutamine
      utilization hence critical in metabolic disorders that involve energy balance
      such as diabetes. This study investigates the effects of oleanolic acid (OA) on
      SI morphology and some enzymes of glutamine metabolism in male Sprague-Dawley
      diabetic rats. High dose STZ-induced diabetes (HDD) and low dose STZ-induced
      diabetes (LDD) were induced by intraperitoneal injection of 60 and 40 mg
      streptozotocin/kg body weight respectively. Non-diabetic and diabetic rats were
      treated for two weeks with OA, insulin or OA + insulin in HDD study while animals
      in the in LDD study were treated with OA. There was significant (P<0.05) increase
      in the weight of the SI of diabetic animals and of villus height (VH) in the
      jejunum and duodenum of HDD animals. OA and insulin treatment significantly
      decreased VH in duodenum of HDD animals while OA treatment profoundly increased
      VH in normal rats. Jejunal of phosphate-dependent glutaminase (PDG) activity was
      unaffected by diabetes however alanine aminotransferase, aspartate
      aminotransferase and glutamate dehydrogenase activities were significantly
      (P<0.05) elevated by diabetes and treatments decreased these elevated
      aminotransferase activities. It is suggested that the intestine meets the energy
      demand in diabetes by modulating the activities of aminotransferases without
      change in PDG activity.

PMID- 29209448
TI  - Sirt1 Protects Endothelial Cells against LPS-Induced Barrier Dysfunction.
AB  - Sepsis is a threatening health problem and characterized by microvascular
      dysfunction. In this study, we verified that LPS caused the downregulation of
      Sirt1 and the hyperpermeability of endothelial cells. Inhibition of Sirt1 with
      ex527 or Sirt1 siRNA displayed a higher permeability, while activation of Sirt1
      with SRT1720 reversed the LPS-induced hyperpermeability, formation of fiber
      stress, and disruption of VE-cadherin distribution. In pulmonary microvascular
      vein endothelial cells isolated from wild-type mice, Sirt1 was attenuated upon
      LPS, while Sirt1 was preserved in a receptor of advanced glycation end product
      knockout mice. The RAGE antibody could also diminish the downregulation and
      ubiquitination of Sirt1 in LPS-exposed human umbilical vein endothelial cells. An
      LPS-induced decrease in Sirt1 activity was attenuated by the RAGE antibody and
      TLR4 inhibitor. In vivo study also demonstrated the attenuating role of Sirt1 and
      RAGE knockout in LPS-induced increases in dextran leakage of mesenteric venules.
      Furthermore, activation of Sirt1 prevented LPS-induced decreases in the activity
      and expression of superoxide dismutase 2, as well as the increases in NADPH
      oxidase 4 and reactive oxygen species, while inhibition of Sirt1 aggravated the
      SOD2 decline. It also demonstrated that Sirt1-deacetylated p53 is required for
      p53 inactivation, which reversed the downregulation of beta-catenin caused by
      LPS.

PMID- 29209450
TI  - Zinc chelation promotes streptokinase-induced thrombolysis in vitro.
AB  - Cardiovascular disorder occurs when a local blood clot obstructs an artery or a
      vein to its surround organs, causing related tissues to lose function and die. It
      is one of the leading causes of mortality and a major cause of disability. The
      effect of thrombolysis induced by injecting intravenous thrombolytic agents is
      critical for reducing tissue damages. Streptokinase (SK) is a widely used
      thrombolytic agent in the treatment of thromboembolism in the blood vessels. A
      high unit of streptokinase is used in thrombolytic therapies for thrombotic
      disorders and could improve tissue reperfusion. It is a potent plasminogen
      activator. However, safety concerns for the usage of a high unit of streptokinase
      have been raised for the hemorrhagic transformation. In the present study, we
      studied how zinc would affect streptokinase-induced thrombolysis in vitro, and
      proposed a strategy to improve streptokinase's effectiveness in promoting
      thrombolysis. The mice whole blood was used to form the blood clot in vitro by
      incubating with calcium at 37 degrees C for 30 minutes. Streptokinase was used
      for inducing thrombolysis measured with the spectrophotometer. Zinc and its
      chelator, Ca-EDTA, were applied with streptokinase, respectively. Results showed
      that the co-application zinc inhibited the thrombolytic effect of streptokinase
      in a dose-dependent manner. Zinc chelator, Ca-EDTA, significantly increased the
      effect of streptokinase-induced thrombolysis. Our results suggest that zinc
      chelation improved the efficiency of streptokinase in thrombolysis. The results
      may have a significant clinical implication by potentially reducing the adverse
      effect of streptokinase application.

PMID- 29209451
TI  - miR-149 reduces while let-7 elevates ASIC1a expression in vitro.
AB  - Acid-sensing ion channel 1a (ASIC1a) is the key subunit that determines acid
      activated currents in neurons. ASIC1a is important for neural plasticity,
      learning, and for multiple neurological diseases, including stroke, multiple
      sclerosis, and traumatic injuries. These findings underline the importance for
      better defining mechanisms that regulate ASIC1a expression. During the past
      decade, microRNA has emerged as one important group of regulatory molecules in
      controlling protein expression. However, little is known about whether microRNA
      regulates ASIC1a. Here, we assessed several microRNAs that have predicted
      targeting sequences in the 3' untranslated region (UTR) of mouse ASIC1a. Our
      results indicated that miR-144 and -149 reduced ASIC1a expression while Let-7
      increased ASIC1a protein levels. miR-30c, -98, -125, -182* had no significant
      effect. Since a reduction in ASIC1a expression may have translational potentials
      in treating neuronal injury, we further asked whether the effect of miR-144 and
      miR-149, both reduced ASIC1a expression, was through specific targeting of the
      predicted sites on ASIC1a. We mutated the targeting sequence of miR-144 and miR
      149 in ASIC1a UTR. The effect of miR-149 was abolished in the corresponding
      mutation. In contrast, miR-144 still reduced ASIC1a level when its predicted
      target sequence was mutated. This result indicates that miR-149 targets the 3'UTR
      of ASIC1a and reduces its expression.

PMID- 29209452
TI  - Protective roles of hepatic GABA signaling in liver injury.
AB  - In addition to functioning as a neurotransmitter, gamma-aminobutyric acid (GABA)
      generates signals, via its type A or type B receptors (GABAARs or GABABRs), in
      various types of cells. Studies, including ours, show that GABAAR-mediated auto-
      and paracrine GABAergic signaling occurs in rodent hepatocytes and
      cholangiocytes, protecting the liver against toxic injuries. This short article
      briefly introduces the GABA signaling system in rodent livers and discusses
      potential mechanisms by which the hepatic GABA signaling protects the liver
      function.

PMID- 29209453
TI  - Statistical methods and common problems in medical or biomedical science
      research.
AB  - Statistical thinking is crucial for studies in medical and biomedical areas.
      There are several pitfalls of using statistics in these areas involving in
      experimental design, data collection, data analysis and data interpretation. This
      review paper describes basic statistical design problems in biomedical or medical
      studies and directs the basic scientists to better use of statistical thinking.
      The contents of this paper were based on previous literatures and our daily basic
      support work. It includes the sample size determination and sample allocation in
      experimental design stage, numerical and graphical data summarization, and
      statistical test methods as well as the related common errors at design and
      analytic stages. Literatures and our daily support works show that
      misunderstanding and misusing of statistical concept and statistical test methods
      are significant problems. These may include ignoring the sample size and data
      distribution, incorrect summarization measurement, wrong statistical test methods
      especially for repeated measures, ignoring the assumption for t-test or ANOVA
      test, failing to perform the adjustment for multiple comparison. This review
      intends to help the researchers in basic medical or biomedical areas to enhance
      statistical thinking and make fewer errors in study design and analysis of their
      studies.

PMID- 29209454
TI  - Kimchi attenuates fatty streak formation in the aorta of low-density lipoprotein
      receptor knockout mice via inhibition of endoplasmic reticulum stress and
      apoptosis.
AB  - BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress is positively associated
      with atherosclerosis via elevating macrophage cell death and plaque formation, in
      which oxidative stress plays a pivotal role. Antioxidative, lipid-lowering, and
      anti-atherogenic effects of kimchi, a Korean fermented vegetable, have been
      established, wherein capsaicin, ascorbic acid, quercetin, 3-(4'-hydroxyl-3',5'
      dimethoxyphenyl)propionic acid, and lactic acids were identified. In this study,
      mechanisms of action of kimchi methanol extracts (KME) on fatty streak formation
      via suppression of ER stress and apoptosis in aorta were examined in low-density
      lipoprotein receptor knockout mice. MATERIALS AND METHODS: Mice fed a high
      cholesterol diet with an oral administration of KME (KME group, 200 mg.kg-bw
      1.day-1) or distilled water (control group) for 8 weeks (n = 20 for group).
      Plasma lipid and oxidative stress levels were evaluated. Protein expression was
      measured by western blot assay. Fatty streak lesion size and the degree of
      apoptosis were examined in the aorta. RESULTS: Compared to the control group, in
      the KME group, plasma lipids levels were decreased and oxidative stress was
      alleviated (P < 0.05). Protein expression levels of nuclear factor (erythroid
      derived 2)-like 2-mediated antioxidants in aorta were increased whereas those for
      ER stress markers, glucose regulated protein 78, phospho-protein kinase RNA-like
      ER kinase, phospho-eukaryotic initiation factor 2 subunit alpha, X-box binding
      protein 1, and C/EBP homologous protein were decreased in the KME group (P <
      0.05). Moreover, apoptosis was suppressed via downregulation of phospho-c-Jun N
      terminal kinase, bcl-2-associated X protein, caspases-9, and -3 with a
      concomitant upregulation of anti-apoptotic protein, B-cell lymphoma 2 (P < 0.05).
      Fatty streak lesion size was reduced and the degree of apoptosis was less severe
      in the KME group (P < 0.05). CONCLUSIONS: In conclusion, antioxidant activity of
      KME might prevent fatty streak formation through, in part, inhibition of ER
      stress and apoptosis in aortic sinus where macrophages are harbored.

PMID- 29209455
TI  - Acute and 13-week subchronic toxicological evaluations of turanose in mice.
AB  - BACKGROUND/OBJECTIVES: Turanose, alpha-D-glucosyl-(1->3)-alpha-D-fructose, is a
      sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose,
      acute and subchronic oral toxicity studies were conducted with ICR mice.
      MATERIALS AND METHODS: For the acute oral toxicity study, turanose was
      administered as a single oral dose [10 g/kg body weight (b.w.)]. In the
      subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg
      b.w. doses of turanose daily for 13 weeks. RESULTS: No signs of acute toxicity,
      including abnormal behavior, adverse effect, or mortality, were observed over the
      14-day study period. In addition, no changes in body weight or food consumption
      were observed and the median lethal dose (LD50) for oral intake of turanose was
      determined to be greater than 10 g/kg b.w. General clinical behavior, changes in
      body weight and food consumption, absolute and relative organ weights, and
      mortality were not affected in any of the treatment group for 13 weeks. These
      doses also did not affect the macroscopic pathology, histology, hematology, and
      blood biochemical analysis of the mice examined. CONCLUSION: No toxicity was
      observed in the acute and 13-week subchronic oral toxicology studies that were
      conducted with ICR mice. Furthermore, the no-observed-adverse-effect level is
      greater than 7 g/kg/day for both male and female ICR mice.

PMID- 29209456
TI  - Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus
      overproduction in a murine model of asthma.
AB  - BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and
      alveolar macrophages is a characteristic feature of asthma that leads to
      pathological subepithelial thickening and remodeling. Our previous study showed
      that oxidative stress in airways resulted in eosinophilia and epithelial
      apoptosis. The current study investigated whether glutathione-containing dry
      yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and
      mucus overproduction. MATERIALS/METHOD: This study employed 2 ug/mL
      lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial
      epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this
      study contained a significant amount of glutathione (140 mg in 100 g dry yeast).
      RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were
      markedly induced by the endotoxin LPS, which was dose-dependently attenuated by
      nontoxic dry-YE at 10-50 ug/mL. Moreover, dry-YE inhibited the MUC5AC induction
      enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt
      the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited
      inflammatory cell accumulation in airway subepithelial regions with a reduction
      of lung tissue level of intracellular adhesion molecule-1. In addition, >= 50
      mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major
      basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff
      staining revealed that the dry-YE supplementation inhibited goblet cell
      hyperplasia and mucus overproduction in the trachea and bronchiolar airways of
      OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the
      induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE
      effectively ameliorated oxidative stress-responsive epithelial eosinophilia and
      mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

PMID- 29209457
TI  - Anti-fibrotic effects of Orostachys japonicus A. Berger (Crassulaceae) on hepatic
      stellate cells and thioacetamide-induced fibrosis in rats.
AB  - BACKGROUND/OBJECTIVE: Orostachys japonicus A. Berger (Crassulaceae) has been used
      in traditional herbal medicines in Korea and other Asian countries to treat
      various diseases, including liver disorders. In the present study, the anti
      fibrotic effects of O. japonicus extract (OJE) in cellular and experimental
      hepatofibrotic rat models were investigated. MATERIALS/METHODS: An in vitro
      hepatic stellate cells (HSCs) system was used to estimate cell viability, cell
      cycle and apoptosis by MTT assay, flow cytometry, and Annexin V-FITC/PI staining
      techniques, respectively. In addition, thioacetamide (TAA)-induced liver fibrosis
      was established in Sprague Dawley rats. Briefly, animals were divided into five
      groups (n = 8): Control, TAA, OJE 10 (TAA with OJE 10 mg/kg), OJE 100 (TAA with
      OJE 100 mg/kg) and silymarin (TAA with Silymarin 50 mg/kg). Fibrosis was induced
      by treatment with TAA (200 mg/kg, i.p.) twice per week for 13 weeks, while OJE
      and silymarin were administered orally two times per week from week 7 to 13. The
      fibrotic related gene expression serum biomarkers glutathione and hydroxyproline
      were estimated by RT-PCR and spectrophotometry, respectively, using commercial
      kits. RESULTS: OJE (0.5 and 0.1 mg/mL) and silymarin (0.05 mg/mL) treatment
      significantly (P < 0.01 and P < 0.001) induced apoptosis (16.95% and 27.48% for
      OJE and 25.87% for silymarin, respectively) in HSC-T6 cells when compared with
      the control group (9.09%). Further, rat primary HSCs showed changes in morphology
      in response to OJE 0.1 mg/mL treatment. In in vivo studies, OJE (10 and 100
      mg/kg) treatment significantly ameliorated TAA-induced alterations in levels of
      serum biomarkers, fibrotic related gene expression, glutathione, and
      hydroxyproline (P < 0.05-P < 0.001) and rescued the histopathological changes.
      CONCLUSIONS: OJE can be developed as a potential agent for the treatment of
      hepatofibrosis.

PMID- 29209458
TI  - The effects of daily intake timing of almond on the body composition and blood
      lipid profile of healthy adults.
AB  - BACKGROUND/OBJECTIVES: Timing of almond intake during a day may result
      differently in the perspectives of body composition and changes of lipid profile.
      The current study was conducted to compare the effects of daily almond intake as
      a preload versus as a snack on body composition, blood lipid profile, and
      oxidative and inflammation indicators among young Korean adults aged 20-39 years
      old. SUBJECTS/METHODS: Participants were randomly assigned to one of three
      groups: a pre-meal almond group (PM), a snack almond group (SN) in which
      participants were instructed to consume 56 g of almonds either as a preload
      before meals or as a snack between meals, respectively, and a control group (CL)
      in which participants were provided high-carbohydrate iso-caloric control food.
      Measurements were performed at baseline, weeks 8 and 16. RESULTS: A total of 169
      (M 77/F 92) out of the 227 participants completed the study between June 2014 and
      June 2015 (n = 58 for PM; 55 for SN; and 56 for CL). A significant decrease in
      body fat mass was observed in the PM group at both weeks 8 and 16 compared with
      the CL. There were significant intervention effects on changes of body fat mass
      (P = 0.025), body fat percentages (P = 0.019), and visceral fat levels (P <
      0.001). Consuming almonds as a daily snack reduced the levels of total
      cholesterol (P = 0.043) and low-density lipoprotein (LDL) cholesterol (P = 0.011)
      without changing high-density lipoprotein (HDL) cholesterol compared with the CL.
      CONCLUSION: Almond consumption as a preload modified body fat percentages,
      whereas snacking on almonds between meals improved blood lipid profiles. This
      trial was registered at ClinicalTrials.gov as NCT03014531.

PMID- 29209459
TI  - Effects of zinc supplementation on catch-up growth in children with failure to
      thrive.
AB  - BACKGROUND/OBJECTIVES: Although globally the numbers of children diagnosed with
      failure to thrive (FTT) have decreased, FTT is still a serious pediatric problem.
      We aimed to investigate the effects of zinc supplementation for 6 months on
      growth parameters of infants and children with FTT. SUBJECTS/METHODS: In this
      retrospective study, of the 114 participants aged between 4 months and 6 years,
      89 were included in the zinc supplementation group and were provided with
      nutrition counseling plus an oral zinc supplement for 6 months. The caregivers of
      the 25 participants in the control group received nutrition counseling alone.
      Medical data of these children, including sex, age, height, weight, serum zinc
      level, and serum insulin-like growth factor 1 (IGF1) level were analyzed.
      RESULTS: Zinc supplementation for 6 months increased weight-for-age Z-score and
      serum zinc levels (5.5%) in the zinc supplementation group of underweight
      category children. As for stunting category, height-for-age Z-score of the
      participants in the zinc supplementation group increased when compared with the
      baseline, and serum zinc levels increased in the normal or mild stunting group.
      Serum IGF1 levels did not change significantly in any group. Thus, zinc
      supplementation was more effective in children in the underweight category than
      those in the stunted category; this effect differed according to the degree of
      the FTT. CONCLUSION: These findings suggest that zinc supplementation may have
      beneficial effects for growth of infants and children with FTT, and zinc
      supplementation would be required according to degree of FTT.

PMID- 29209460
TI  - Association of dietary patterns with overweight risk and all-cause mortality in
      children with cancer.
AB  - BACKGROUND/OBJECTIVES: This study aimed to investigate the association of dietary
      patterns with overweight risk and all-cause mortality in pediatric cancer
      patients. SUBJECTS/METHODS: Prospective cohort study was undertaken; 83 cancer
      patients admitted to the pediatric cancer ward at a university hospital in Seoul
      were included and followed for obesity and death over 24 months. Food consumption
      data were collected from patients using validated meal order sheets for
      breakfast, lunch, and dinner at the pediatric cancer ward over 3 days. Using
      principal component analysis, three dietary patterns were derived from 29 food
      groups. RESULTS: Eighteen deaths occurred among the patient cohort during the
      follow-up period. The "spicy & fried meat and fish" dietary pattern was
      positively associated with overweight risk at both baseline [odds ratio (OR) =
      4.396, 95% confidence interval (CI) = 1.111-17.385, P for trend = 0.023] and
      after 6 months (OR = 4.088, 95% CI = 1.122-14.896, P for trend = 0.025) as well
      as all-cause mortality (hazard ratios = 5.124, 95% CI = 1.080-24.320, P for trend
      = 0.042), when comparing the highest and lowest tertiles after adjusting for
      covariates. The "fish, egg, meat, and fruits & vegetables" dietary pattern was
      associated with lower overweight risk after 24 months (OR = 0.157, 95% CI = 0.046
      0.982, P for trend = 0.084). CONCLUSION: The results imply that dietary patterns
      might be associated with weight gain and premature death among pediatric cancer
      patients.

PMID- 29209461
TI  - Selection of key foods for the systematic management of a food and nutrient
      composition database.
AB  - BACKGROUND/OBJECTIVES: Food composition databases are necessary for assessing
      dietary intakes. Developing and maintaining a high quality database is difficult
      because of the high cost of analyzing nutrient profiles and the recent fast
      changing food marketplace. Thus, priorities have to be set for developing and
      updating the database. We aimed to identify key foods in the Korean diet to set
      priorities for future analysis of foods. SUBJECTS/METHODS: modified the US
      Department of Agriculture's key food approach. First, major foods were analyzed,
      contributing to 75%, 80%, 85%, or 90% of each nutrient intake. Second, the
      cumulative contributions to nutrient intakes were compared before and after
      excluding the foods least commonly consumed by individuals. Third, total nutrient
      score for each food was calculated by summing all percent contributions times 100
      for nutrients. To set priorities among the foods in the list, we sorted the score
      in descending order and then compared total percent contributions of foods,
      within the 100, 90, 85, 80, and 75 percentiles of the list. Finally, we selected
      the minimum list of foods contributing to at least 90% of the key nutrient intake
      as key items for analysis. RESULTS: Among the 1,575 foods consumed by
      individuals, 456 were selected as key foods. Those foods were chosen as items
      above the 80 percentile of the total nutrient score, among the foods contributing
      at least 85% of any nutrient intake. On an average, the selected key foods
      contributed to more than 90% of key nutrient intake. CONCLUSIONS: In total, 456
      foods, contributing at least 90% of the key nutrient intake, were selected as key
      foods. This approach to select a minimum list of key foods will be helpful for
      systematically updating and revising food composition databases.

PMID- 29209462
TI  - Dietary intakes of adolescents from food insecure households: analysis of data
      from the 6th (2013-2015) Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND/OBJECTIVES: This study aimed at evaluating the dietary intakes of
      Korean adolescents affected by food insecurity, in comparison with those who were
      food secure. SUBJECTS/METHODS: The study used one day 24-hour dietary recall data
      from the 6th Korea National Health and Nutrition Examination Survey. The study
      subjects consisted of 1,453 adolescents of whom 695 were middle school-aged and
      758 were high school-aged. Food security status was assessed using the 18-item
      questionnaire. Nutrient intake was evaluated in terms of nutrient density,
      insufficient intake, and excessive intake for selected nutrients, in addition to
      meeting the appropriate range for total energy intake and energy intakes from
      carbohydrate, sugar, protein, fat, and saturated fatty acids. Food intake was
      evaluated in terms of food group servings and dietary diversity score (DDS).
      RESULTS: The percentages of food insecurity were 11.1% for middle school-aged
      adolescents and 16.8% for high school-aged adolescents. Food insecure middle
      school-aged adolescents had higher intake of carbohydrate (P = 0.006) but lower
      intake of fat (P = 0.010) and saturated fatty acids (P = 0.005) than their food
      secure counterparts although the intake of both groups was in the recommended
      ranges. Nutrient intake among high school-aged adolescents was generally similar
      regardless of food security status. Both food secure and insecure adolescents
      showed insufficient intake of vitamin A, vitamin C, and calcium, and excessive
      sodium intake. They additionally had low prevalence of meeting appropriate intake
      ranges for energy, carbohydrate, and sugar. Food intake in terms of food group
      servings and DDS was also similar regardless of food security status among both
      age groups, with low intakes of foods from fruit and dairy groups. CONCLUSIONS:
      Except for a few nutrients among the middle school-aged adolescents, dietary
      intakes among Korean adolescents did not differ by food security status in this
      study.

PMID- 29209463
TI  - Eating patterns of children's favorite foods and its related factors among
      elementary, middle, and high school students in Korea.
AB  - BACKGROUND/OBJECTIVES: There are limited studies investigating the eating
      patterns of children's favorite foods. The present study aimed to evaluate a wide
      range of children's favorite foods, derive its eating patterns, and identify
      factors related to the patterns. SUBJECTS/METHODS: A nationwide cross-sectional
      study included 5,458 students in elementary, middle, and high schools. The survey
      was conducted at each school to evaluate children's favorite food intake,
      including the intake frequency of 31 food items or food groups, and its related
      factors, such as demographic, economic, and environmental characteristics and
      awareness of policies on children's favorite foods. Factor analysis using varimax
      rotation method and logistic regression analysis were conducted. RESULTS: Two
      factors were derived as major eating patterns from data of children's favorite
      foods: the 'unhealthy eating pattern' which mainly involves confectionery,
      chocolate, ramen, fried food, etc.; and the 'healthy eating pattern' which mainly
      involves soybean milk, vegetables, fruit juice, and nuts. A stepwise selection
      procedure through the regression analysis revealed that allowance, use of screen
      media, less awareness of policies on children's favorite foods, and less interest
      in health were positively related to the tendency of unhealthy or less-healthy
      eating patterns (P < 0.05). CONCLUSIONS: This study examined that the eating
      patterns of children's favorite foods were associated with certain environmental
      characteristics and awareness about the related policies. These findings suggest
      that a nutrition education program regarding children's favorite foods needs to
      be conducted according to the characteristics of students to develop their
      healthy eating habits and proper choice of favorite foods.

PMID- 29209464
TI  - Erratum: Agrobacterium sp.-derived beta-1,3-glucan enhances natural killer cell
      activity in healthy adults: a randomized, double-blind, placebo-controlled,
      parallel-group study.
AB  - [This corrects the article on p. 43 in vol. 11, PMID: 28194264.].

PMID- 29209466
TI  - Peritraumatic dissociation predicts posttraumatic stress disorder symptoms via
      dysfunctional trauma-related memory among war-affected children.
AB  - Background: Among adults there is strong evidence about peritraumatic
      dissociation (PD) predicting posttraumatic stress disorder (PTSD), yet evidence
      among children is very limited. It has been suggested that disturbances in memory
      functioning might explain the association between PD and PTSD, but this has not
      yet been empirically tested. Objective: We aimed to test the hypotheses that
      greater PD would be associated with more posttraumatic stress disorder (PTSD)
      symptoms, and that some of this association would be mediated by disorganized and
      non-verbal memories about the traumatic event. Method: The sample included 197
      Palestinian children (10-12-years) living in the Gaza Strip, participating in the
      aftermath of the 2008/9 war. Self-report questionnaires were used to measure PD
      (Peritraumatic Dissociative Experiences Questionnaire) three months post-war, as
      well as trauma-related memory (Trauma Memory Quality Questionnaire) and PTSD
      symptoms (Children's Revised Impact of Event Scale) six months later. Exposure to
      war trauma was assessed by a checklist. Structural equation modelling was used to
      examine direct and indirect paths from PD to posttraumatic PTSS, controlling for
      number of traumatic war events. Results: Structural equation modelling results
      showed that greater self-reported PD predicted higher levels of PTSS nine months
      post-war, and that a significant part, but not all, of this relationship was
      mediated via the quality of trauma-related memories. Conclusions: This study
      provided empirical evidence that, among war-affected children, greater PD during
      traumatic events is linked with higher levels of PTSD symptoms several months
      later, even when accounting for their personal exposure to war trauma. Further,
      the study supported the idea that the detrimental effects of dissociation during
      a traumatic event may be due to dysfunctional memories characterized by
      disorganization and lack of access to verbal and coherence. Further tests of
      these hypotheses with larger samples and more points of measurement are called
      for.

PMID- 29209465
TI  - Two-component signal transduction systems in oral bacteria.
AB  - We present an overview of how members of the oral microbiota respond to their
      environment by regulating gene expression through two-component signal
      transduction systems (TCSs) to support conditions compatible with homeostasis in
      oral biofilms or drive the equilibrium toward dysbiosis in response to
      environmental changes. Using studies on the sub-gingival Gram-negative anaerobe
      Porphyromonas gingivalis and Gram-positive streptococci as examples, we focus on
      the molecular mechanisms involved in activation of TCS and species specificities
      of TCS regulons.

PMID- 29209468
TI  - Cardiovascular Risk Assessment Based on Combined Body Mass Index and Waist
      Circumference in Korean Adults.

PMID- 29209469
TI  - Probability or Reasoning: Current Thinking and Realistic Strategies for Improved
      Medical Decisions.
AB  - A prescriptive model approach in decision making could help achieve better
      diagnostic accuracy in clinical practice through methods that are less reliant on
      probabilistic assessments. Various prescriptive measures aimed at regulating
      factors that influence heuristics and clinical reasoning could support clinical
      decision-making process. Clinicians could avoid time-consuming decision-making
      methods that require probabilistic calculations. Intuitively, they could rely on
      heuristics to obtain an accurate diagnosis in a given clinical setting. An
      extensive literature review of cognitive psychology and medical decision-making
      theory was performed to illustrate how heuristics could be effectively utilized
      in daily practice. Since physicians often rely on heuristics in realistic
      situations, probabilistic estimation might not be a useful tool in everyday
      clinical practice. Improvements in the descriptive model of decision making
      (heuristics) may allow for greater diagnostic accuracy.

PMID- 29209470
TI  - The Effect of Having a Regular Doctor as a Primary Care Provider on Emergency
      Room Utilization in South Korea.
AB  - Background: Because primary care is the cornerstone of an effective health care
      system, many developed countries have striven to establish and strengthen their
      primary care systems. However, the primary care system in South Korea is not well
      established, and primary care research is still in its infancy. This study aimed
      to show the benefits of regular doctors as primary care providers in South Korea
      by analyzing the effect of regular doctor visits on emergency room (ER) visits.
      Methods: We analyzed cross-sectional data on 11,293 adults aged 18 years and over
      collected from the 2013 Korea Health Panel Survey (beta version 1.0). We
      classified those participants with and without regular doctors into the treatment
      and control groups, respectively, and estimated the average treatment effect
      (ATE) of having a regular doctor on ER visits. We used counterfactual framework
      and propensity score analysis to adjust for unevenly distributed confounding
      covariates between treatments and control groups. Results: The estimated
      conditional ATE of a regular doctor on ER visits was statistically insignificant
      in the general population (-0.4%; 95% confidence interval [CI], -2.0 to 1.2) and
      in the subgroup of patients with hypertension (-1.8%; 95% CI, -4.5 to 0.9).
      However, in patients with diabetes mellitus (DM), the estimated ATE was
      statistically significant (-5.0; 95% CI, -9.2 to -0.7). Conclusion: In the total
      study population, having a regular doctor did not result in a significant
      difference in ER visits. However, there was a decrease in ER visits in patients
      with DM in South Korea.

PMID- 29209471
TI  - General Practitioners' Perceptions on Clinical Management and Training Needs
      regarding the Healthcare of Community-Dwelling People with Intellectual
      Disability: A Preliminary Survey in Singapore.
AB  - Background: Studies worldwide indicate that people with intellectual disability
      have high risks of physical and mental morbidities, and poor quality of health
      care. This study was aimed at determining general practitioners' perceptions on
      barriers in clinical assessment and training needs with regard to the healthcare
      of community-dwelling people with intellectual disability. Methods: A survey
      questionnaire was developed specifically for the study through focus group
      discussions and a literature review. The study was conducted as a cross-sectional
      anonymous survey of private general practitioners practicing in Singapore. The
      survey contained questions on their experience and training needs in assessing
      and treating patients with intellectual disability. Results: Forty-nine of the
      272 questionnaires sent out were returned. The respondents were predominantly
      male general practitioners working in "solo" practices. For most general
      practitioners, the proportion of patients with intellectual disability ranged
      from 1% to 5%. Nearly 90% of general practitioners identified problems in
      communicating with such patients as an important barrier that affected the
      quality of assessment of their health conditions. Other barriers identified were
      behavioral issues and sensory impairments. Only one-third of the general
      practitioners were confident that they had sufficient knowledge of physical and
      mental health conditions related to patients with intellectual disability. Three
      fourths of the general practitioners believed that further training in this area
      would be beneficial. Conclusion: Appropriate interventions to address barriers in
      assessment and management of patients with intellectual disability with further
      training for general practitioners may improve the standard of healthcare
      provided to this population group.

PMID- 29209467
TI  - Biological roles and potential applications of immune cell-derived extracellular
      vesicles.
AB  - Extracellular vesicles (EVs) deliver bioactive macromolecules (i.e. proteins,
      lipids and nucleic acids) for intercellular communication in multicellular
      organisms. EVs are secreted by all cell types including immune cells. Immune cell
      derived EVs modulate diverse aspects of the immune system to either enhance or
      suppress immune activities. The extensive effects of immune cell-derived EVs have
      become the focus of great interest for various nano-biomedical applications,
      ranging from the medical use of nanoplatform-based diagnostic agents to the
      development of therapeutic interventions as well as vaccine applications, and
      thus may be ideal for 'immune-theranostic'. Here, we review the latest advances
      concerning the biological roles of immune cell-derived EVs in innate and acquired
      immunity. The intercellular communication amongst immune cells through their EVs
      is highlighted, showing that all immune cell-derived EVs have their unique
      function(s) in immunity through intricate interaction(s). Natural-killer (NK)
      cell-derived EVs, for example, contain potent cytotoxic proteins and induce
      apoptosis to targeted cancer cells. On the other hand, cancer cell-derived EVs
      bearing NK ligands may evade immune surveillance and responses. Finally, we
      discuss possible medical uses for the immune cell-derived EVs as a tool for
      immune-theranostic: as diagnostic biomarkers, for use in therapeutic
      interventions and for vaccination.

PMID- 29209472
TI  - Uric Acid Level Has a J-Shaped Association with Arterial Stiffness in Korean
      Postmenopausal Women.
AB  - Background: Uric acid has been reported to function both as an oxidant or
      antioxidant depending on the context. A previous study in the Korean population
      reported a positive linear association between serum uric acid level and arterial
      stiffness in men, but little is known about how serum uric acid level is related
      to the risk of increased arterial stiffness in Korean postmenopausal women.
      Methods: We performed a cross-sectional study of 293 subjects who participated in
      a health examination program run by the health promotion center of Gangnam
      Severance Hospital between October 2007 and July 2010. High brachial-ankle pulse
      wave velocity was defined as a brachial-ankle pulse wave velocity of more than
      1,450 cm/s. The odds ratios (ORs) for high brachial-ankle pulse wave velocity
      were calculated using multivariate logistic regression analysis across uric acid
      quartiles after adjusting for other indicators of cardiovascular risk. Results:
      The 293 postmenopausal women were divided into quartiles according to uric acid
      level. The mean brachial-ankle pulse wave velocity values of each quartile were
      as follows: Q1, 1,474 cm/s; Q2, 1,375 cm/s; Q3, 1,422 cm/s; Q4, 1,528 cm/s. The
      second quartile was designated as the control group based on mean brachial-ankle
      pulse wave velocity value. Multivariate adjusted ORs (95% confidence intervals)
      for brachial-ankle pulse wave velocity across the uric acid quartiles were 2.642
      (Q1, 1.095-6.3373), 1.00, 4.305 (Q3, 1.798-10.307), and 4.375 (Q4, 1.923-9.949),
      after adjusting for confounding variables. Conclusion: Serum uric acid level has
      a J-shaped association with arterial stiffness in Korean postmenopausal women.

PMID- 29209473
TI  - Correlation of Cardiovascular Risk Factors with Central Obesity and Multiple Body
      Mass Index in Korea.
AB  - Background: Body mass index (BMI) and waist circumference (WC) are associated
      with cardiovascular (CV) risk factors. The aim of this study was to investigate
      the correlation of CV risk factors by cross-tabulating central obesity with
      multiple BMI categories in Korea. Methods: A total of 328,789 adults aged 30-84
      years who completed health assessments for National Health Insurance in 2012-2013
      in Korea were examined. The participants were divided into two WC and five BMI
      groups to investigate CV risk factors, including metabolic syndrome (MetS),
      hypertension, diabetes, and dyslipidemia. Results: The proportions of central
      obesity and obesity were 24.2% and 39.5% in men and 19.4% and 28.1% in women,
      respectively, according to the Korean Society for the Study of Obesity and World
      Health Organization Asia-Pacific Guideline criteria. The odds ratios (ORs) of CV
      risk factors in all sexes increased with increases in BMI and WC. Compared to the
      group with a normal WC and BMI, the adjusted ORs (95% confidence intervals) for
      having MetS and diabetes in the centrally obese and highest BMI group (BMI >=30.0
      kg/m2) were 35.95 (33.75-38.30) and 3.51 (3.26-3.77) in men and 29.22 (27.36
      31.20) and 4.35 (4.02-4.70) in women, respectively. Participants who were
      centrally obese and obese (BMI >=25.0 kg/m2) had the strongest correlation with
      all CV risk factors compared with those who were not centrally obese or obese.
      Conclusion: The presence of central obesity in multiple BMI categories may
      significantly identify individuals at increased risk of CV risk factors.

PMID- 29209475
TI  - The Relationship between the Triglyceride to High-Density Lipoprotein Cholesterol
      Ratio and Metabolic Syndrome.
AB  - Background: Metabolic syndrome is associated with cardiovascular diseases and is
      characterized by insulin resistance. Recent studies suggest that the
      triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predicts
      insulin resistance better than individual lipid levels, including TG, total
      cholesterol, low-density lipoprotein cholesterol (LDLC), or HDLC. We aimed to
      elucidate the relationship between the TG/HDLC ratio and metabolic syndrome in
      the general Korean population. Methods: We evaluated the data of adults >=20
      years old who were enrolled in the Korean National Health and Nutrition
      Examination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial
      infarction, stroke, or cancer were excluded. Metabolic syndrome was defined by
      the harmonized definition. We examined the odds ratios (ORs) of metabolic
      syndrome according to TG/HDLC ratio quartiles using logistic regression analysis
      (SAS ver. 9.4; SAS Institute Inc., Cary, NC, USA). Weighted complex sample
      analysis was also conducted. Results: We found a significant association between
      the TG/HDLC ratio and metabolic syndrome. The cutoff value of the TG/HDLC ratio
      for the fourth quartile was >=3.52. After adjustment, the OR for metabolic
      syndrome in the fourth quartile compared with that of the first quartile was
      29.65 in men and 20.60 in women (P<0.001). Conclusion: The TG/HDLC ratio is
      significantly associated with metabolic syndrome.

PMID- 29209474
TI  - Relationship between Coffee Consumption and Metabolic Syndrome in Korean Adults:
      Data from the 2013-2014 Korea National Health and Nutrition Examination Survey.
AB  - Background: The gradually increasing demand for coffee worldwide has prompted
      increased interest in the relationship between coffee and health issues as well
      as a need for research on metabolic syndrome in adults. Methods: Data from 3,321
      subjects (1,268 men and 2,053 women) enrolled in the 2013-2014 Korean National
      Health and Nutrition Examination Survey were analyzed. The subjects were divided
      into three groups according to their daily coffee consumption. The odds ratios
      (ORs) and 95% confidence intervals (95% CIs) for metabolic syndrome in the coffee
      drinking groups were calculated using multiple logistic regression analysis by
      adjusting for confounding variables. Results: The prevalence of metabolic
      syndrome was 15.5%, 10.7%, and 9.7% in men and 3.0%, 7.1%, and 6.5% in women
      according to their coffee consumption (less than one, one or two, or more than
      three cups of coffee per day), respectively. Compared with the non-coffee
      consumption group, the ORs (95% CIs) for metabolic syndrome in the group that
      consumed more than three cups of coffee was 0.638 (0.328-1.244) for men and 1.344
      (0.627-2.881) for women after adjusting for age, body mass index, household
      income, education, smoking, alcohol, regular exercise, and daily caloric intake.
      Conclusion: The OR of metabolic syndrome was not statistically significant in
      both men and women.

PMID- 29209476
TI  - Osteoarthritis Affects Health-Related Quality of Life in Korean Adults with
      Chronic Diseases: The Korea National Health and Nutritional Examination Surveys
      2009-2013.
AB  - Background: Osteoarthritis (OA) is a chronic disease that commonly afflicts the
      elderly. This disease reduces the health-related quality of life (HRQoL) and
      causes a significant social burden. Whether the effect of coexisting chronic
      conditions on HRQoL varies according to the presence of OA remains unclear.
      Therefore, this study aimed to investigate this notion. Methods: A total of
      13,395 participants were identified from the 2009-2013 Korean National Health and
      Nutrition Examination Survey for analysis. HRQoL was assessed using the European
      quality of life-5 dimensions (EQ-5D) index. Patients with OA were defined as
      those diagnosed by a physician or those who displayed both, symptoms and
      radiological findings consistent with OA at the time of the survey. Associations
      between OA and 8 chronic conditions were tested using regression analysis.
      Results: The EQ-5D index was lower in patients with OA than in those without
      (mean difference, -0.145; 95% confidence interval [CI], -0.138 to -0.151;
      P<0.001). Most patients with OA and chronic conditions showed a lower score than
      those without. EQ-5D was particularly lower in OA patients with hypertension,
      dyslipidemia, stroke, and renal failure. The estimated beta coefficient for the
      interaction term was significant in renal failure (-0.034; 95% CI, -0.055 to 
      0.012), after adjusting for demographic and socio-economic variables. Conclusion:
      OA significantly affects HRQoL of Korean elderly individuals alone or when
      combined with other conditions. OA combined with renal failure is particularly
      detrimental. These results indicate the importance of managing OA, which is an
      underestimated disease in public health surveys.

PMID- 29209477
TI  - Association of Occupational Class with Healthcare Utilization among Economically
      Active Korean Adults from 2006 to 2014: A Repeated Cross-Sectional Study of
      Koreans Aged 19 Years and Older.
AB  - Background: To investigate the impact of indicators of occupational class on
      healthcare utilization by using longitudinal data from a nationally
      representative survey. Methods: Data were obtained from the Korean Welfare Panel
      Study conducted from 2006 (wave 1) through 2014 (wave 9). A total of 5,104
      individuals were selected at baseline (2006). Analysis of variance and
      longitudinal data analysis were used to evaluate the following dependent
      variables: number of outpatient visits and number of days spent in the hospital
      per year. Results: The number of annual outpatient visits was 4.298 days higher
      (P<0.0001) in class IV, 0.438 days higher (P=0.027) in class III, and 0.335 days
      higher (P=0.035) in class II than in class I. The number of days spent in the
      hospital per year was 0.610 days higher (P=0.001) in class IV, 0.547 days higher
      (P<0.0001) in class III, and 0.115 days higher (P=0.136) in class III than in
      class I. In addition, the number of days spent in the hospital in class IV
      patients with unmet healthcare needs showed an opposite trend to that predicted
      on the basis of socioeconomic status (estimate,-8.524; P-value=0.015).
      Conclusion: Patients whose jobs involved manual or physical labor were
      significantly associated with higher healthcare utilization. Thus, the results
      suggest that healthcare utilization in different occupational classes should be
      improved by monitoring work environments and promoting health-enhancing
      behaviors.

PMID- 29209478
TI  - Association between Sarcopenia and Dipstick Proteinuria in the Elderly
      Population: The Korea National Health and Nutrition Examination Surveys 2009
      2011.
AB  - Background: Sarcopenia and proteinuria are significant health difficulties in the
      elderly; however, few studies have investigated their relationship. In this
      study, we investigated the association between sarcopenia and proteinuria in
      Korean subjects over 60 years old. Methods: We included data from the Korean
      National Health and Nutrition Examination Survey, a cross-sectional, nationally
      representative survey conducted from 2009 to 2011 (n=4,008). Sarcopenia was
      defined using appendicular skeletal muscle mass as a percentage of body weight.
      Proteinuria was defined by a urine dipstick test result above trace levels.
      Results: The overall proteinuria prevalence was 7.2%. The incidence of sarcopenia
      was significantly higher in subjects with proteinuria. The prevalence of
      proteinuria was significantly higher in the sarcopenic group (5.5% vs. 14.5% in
      the non-chronic kidney disease (CKD) group; 17.2% vs. 23.2% in the CKD group)
      than in the non-sarcopenic group. Furthermore, sarcopenic participants had worse
      metabolic parameters, such as higher body mass indexes, waist circumferences, and
      fasting glucose levels, and lower high-density lipoprotein cholesterol levels
      than those in the non-CKD group. After adjustment for confounders, the odds
      ratios (95% confidence interval) for proteinuria were 2.84 (1.92-4.18) in the
      sarcopenic non-CKD group, 3.70 (2.59-5.30) in the non-sarcopenic CKD group, and
      5.19 (2.64-10.18) in the sarcopenic CKD group, compared to the non-sarcopenic,
      non-CKD group. Sarcopenia increased the proteinuria risk in elderly participants
      without CKD, even after adjustment for obesity, hypertension, diabetes, and
      metabolic syndrome. Conclusion: These findings showed that sarcopenia was
      associated with dipstick proteinuria, especially in elderly participants without
      CKD, regardless of comorbidities.

PMID- 29209479
TI  - A Brief Psychotic Episode with Depressive Symptoms in Silent Right Frontal Lobe
      Infarct.
AB  - Psychiatric symptoms may be related to a silent cerebral infarct, a phenomenon
      that has been described previously in literature. Acute psychosis or other
      neuropsychiatric symptoms including depression may present in stroke patients and
      patients with lesions either within the prefrontal or occipital cortices, or in
      subcortical areas such as the basal ganglia, thalamus, mid-brain, and brainstem.
      Psychosis in clinical stroke or in silent cerebral infarction is uncommon and not
      well documented in the literature. Neurological deficits are the most common
      presentation in stroke, and nearly a third of patients that suffer a stroke may
      experience psychological disorders such as depression and anxiety, related to
      physical disability. The present case report describes an elderly female patient
      who presented with hallucinations and depressive symptoms, and was discovered to
      have a recent right frontal brain infarction, without other significant
      neurological deficits.

PMID- 29209480
TI  - The introduction of a video corner in Facts, View & Vision: why and when?

PMID- 29209481
TI  - Endoscopic surgery: One picture worth thousand words.

PMID- 29209482
TI  - The place for prophylactic cerclage in the infertile patient with established
      cervical incompetence who conceived twins after septum reduction.
AB  - Introduction: It is well known that cervical incompetence and associated preterm
      birth confers greater morbidity and mortality on birth outcomes, with an
      additional increased risk of cervical incompetence in higher order gestations.
      While the pathophysiology of cervical incompetence has yet to be elucidated,
      research has identified risk factors and assessed outcomes of numerous
      interventions. Cervical cerclage has been shown, in certain situations involving
      singleton pregnancies, to improve outcomes. Conversely, rescue cerclage increases
      the risk of preterm birth in twin gestations. However, these studies did not
      consider the unique situation of infertile patients, with known cervical
      incompetence, who have utilized assisted reproductive technologies to attain
      pregnancy. This study aims to describe the outcomes of infertile patients with
      known cervical incompetence, carrying twin gestation, who have undergone cervical
      cerclage. Methods: This case series includes eight infertile patients who have
      cervical incompetence resulting in fetal loss between 20-24 weeks after in vitro
      fertilization embryo transfer (IVF-ET). These patients continued with IVF
      treatments and subsequently conceived twins. All patients underwent prophylactic
      cervical cerclage placement before 12 weeks. The outcomes of these pregnancies
      are reviewed. Results: All pregnancies resulted in the delivery of viable twins.
      Six of the eight pregnancies (75%) were carried beyond 34 weeks. One pregnancy
      delivered at 31 weeks and one pregnancy delivered at 25 weeks after placental
      abruption. Conclusions: This data suggest that the use of prophylactic cervical
      cerclage may be beneficial in improving reproductive outcomes in infertile
      patients with known cervical incompetence that subsequently conceived twin
      gestations via IVF-ET treatment.

PMID- 29209483
TI  - Guiding histological assessment of uterine lesions using 3D in vitro
      ultrasonography and stereotaxis.
AB  - Objective: To compare ultrasonographic features of uterine lesions with the
      findings at macroscopy and microscopy. Methods: Case series of ten consecutive
      women undergoing a hysterectomy for uterine pathology. A preoperative
      transvaginal ultrasound examination was performed. After hysterectomy, the uterus
      was re-evaluated by 3D in vitro ultrasonography and in vitro gel instillation
      sonography (iGIS). The lesion of interest was pinpointed by inserting an
      intramuscular injection needle using a free-hand 2D-ultrasound guided technique
      to focus the macroscopic and the microscopic examination by the pathologist.
      Results: Adenomyosis, benign fibroids and infiltrating endometrial cancer were
      diagnosed in six, five and one patient, respectively. We found that iGIS improved
      image quality of in vitro ultrasound. There was a good correlation between the
      reported ultrasound features and the final histological diagnosis. Some lesions
      had been misinterpreted during preoperative ultrasonography or at macroscopical
      examination: e.g. dense myometrial vessels reported as small myometrial cysts at
      grey scale ultrasound examination; absence of macroscopical lesions in a case of
      diffuse adenomyosis. Conclusions: In vitro 3D ultrasonography and iGIS allow for
      accurate mapping of uterine lesions so that ultrasound features can be matched
      with final histology. Our series demonstrates some pitfalls in the interpretation
      of sonographic and macroscopic features of uterine lesions. Stereotaxis of focal
      uterine lesions could focus histological assessment and reduces examination time
      for the pathologist.

PMID- 29209484
TI  - Correlation between saliva and serum concentrations of estradiol in women
      undergoing ovarian hyperstimulation with gonadotropins for IVF/ICSI.
AB  - Aim of the study: To examine saliva- and serum concentrations correlation of
      estradiol (E2) in women undergoing ovarian hyperstimulation for IVF/ICSI. Saliva
      measurements could simplify stimulation follow up. A 'home' test for E2 could be
      useful. Methods: Prospective interventional academic monocentric study at the
      Centre for Reproductive Medicine of the University Hospital of Ghent, Belgium.
      Between November 2014 and August 2015 thirty-one patients were included after
      random selection (inclusion criteria: < 41 years of age, any rank of IVF/ICSI
      cycle, serum anti- Mullerian hormone concentration >= 1 MUg/L, treatment
      completely at the University Hospital.) Measurements took place using immunoassay
      serum measurements. Estradiol was determined in saliva and serum by LC-MS/MS. At
      every control, E2 was measured in saliva and serum. Equilibrium analysis on a
      part of the serum samples took place. Statistic method used is a linear Mixed-
      Effects model (MIXED) in SPSS. Results: Statistical analysis shows a strong
      linear relation between serum and salivary E2, (R2 of 0.75). E2 in equilibrium
      dialysis and E2 in serum were also strong correlated (R2 of 0.85). Conclusions:
      Strong correlation between serum and salivary E2 concentrations was found.
      Equilibrium dialysis showed good correlation with salivary E2. Saliva can be a
      good surrogate for free E2 in women undergoing ovarian hyperstimulation. This may
      create an opportunity to develop a point of care test for measuring E2, in
      purpose to simplify screening for OHSS risk.

PMID- 29209485
TI  - Influence of BMI and smoking on IUI outcome with partner and donor sperm.
AB  - There is limited literature on the influence of smoking and BMI on success rates
      after intrauterine insemination (IUI). As a result of a prospective cohort study
      we could investigate data from 1401 IUI cycles with partner semen and 1264 IUI
      cycles with donor semen, primary outcome being clinical pregnancy rate (CPR).
      Univariate statistical analysis showed significant influence of female BMI on
      clinical pregnancy in the partner insemination group (CPR of 6,5%, 8%, 16,3% and
      9,4% for a female BMI < 20, 20-24.9, 25-29.9 and 3 30, p=0.032), while in the
      donor group this in uence was not signi cant (CPR respectively 11.1% (BMI< 20),
      18.5% (20-24.9), 18.0% (25-29.9) and 14.7% for BMI 3 30). Multivariate analysis
      through generalized estimating equations (GEE) could not confirm this significant
      influence of female BMI on fecundity in the partner semen group. For smoking,
      univariate statistical analysis revealed male smoking to be a negative influence
      for the clinical pregnancy rate in the partner insemination group (10.9% CPR in
      couples with male non-smokers versus 5.9% with male partners smoking 1-14
      cig/day, p=0.017). After multivariate GEE analysis this result remained
      significant (p< 0,01). In the donor semen group female non-smoking or smoking
      less than 15 cigarettes a day turned out to be significantly associated with a
      higher CPR compared to women smoking more than 15 cigarettes daily (16.8% and
      24.5% versus 5.6%, p=0,01). These results were also significant after
      multivariate GEE analysis (p= 0,047 and p= 0,02).

PMID- 29209486
TI  - Impact of the angle used in 2D Ultrasonography on the foetal femur diaphysis
      measurement.
AB  - Objective: The purpose of this pilot study is to compare the 2D scanning
      measurement of the foetal femoral diaphysis using anterior or lateral/external
      incidence at ultrasound. Methods: In August 2016, 30 consecutive patients
      underwent a second trimester morphology ultrasound between 21 and 24 weeks of
      gestation by a senior sonographist. In each case, the femur length was measured
      either with an anterior angle, estimating the straight aspect of the diaphysis or
      with a lateral angle, assessing its curved aspect. The two measures were
      collected prospectively. The difference between paired measurements was
      calculated and expressed in percentage (mm) and in percentile. Results: The
      median difference between the two ultrasound angles in terms of femur length was
      3,55% and in terms of percentile variation was 17,16. Conclusion: An anterior
      angle of measurement of the femur length seems to allow an optimal measure of the
      straight and longest aspect of the diaphysis. According to our results, this
      angle should be considered when scoring the quality of a morphological
      ultrasound, but further and larger studies should be done to confirm our
      hypothesis.

PMID- 29209487
TI  - First steps of laparoscopic surgery in a sub-Saharan African setting: a nine
      month review at the Douala Gynaeco-Obstetric and Pediatric Hospital (Cameroon).
AB  - Objectives: To describe the first laparoscopic surgeries in a tertiary hospital
      in Cameroon. Methods: We carried out a descriptive study at the Douala Gynaeco
      Obstetric and Pediatric Hospital (DGOPH). We examined the files of the 45
      patients who underwent laparoscopic surgery from November 1, 2015 to July 31,
      2016. Descriptive statistics were computed for patients' characteristics and
      surgical parameters. Results: Mean (SD) age was 36.8(11.9) years. Women made up
      86.7% of the sample. Twelve patients (26.7%) had a previous laparotomy. Cash
      deposit (86.7%) was the main mode of payment. Thirty-two (71.1%) laparoscopies
      were gynaeco-obstetrical (GO) and 13 (28.9%) were digestive. Main indications
      were infertility (59.4%) and chronic cholecystitis (30.8%) for GO and digestive
      laparoscopies respectively. Mean (SD) durations were 89.1(57.5) and 55.5(41.0)
      minutes for digestive and GO laparoscopies respectively. Mean (SD) costs were
      1065.4 (406.1) and 934.2 (657.0) USD for digestive and GO laparoscopies
      respectively. Mean (SD) lengths of hospital stays were 5.5 (2.5) and 5.5 (2.5)
      days for digestive and GO laparoscopies respectively. Local staff carried out all
      GO laparoscopies while foreign (Belgian) experts did digestive cases. Only one
      (2.2%) complication (colic perforation) was registered. Conclusion: The
      beginnings of laparoscopy at the DGOPH were successful thanks to strong local
      leadership and Belgian technical assistance.

PMID- 29209488
TI  - Education, early screening and treatment of STIs could reduce infertility among
      women in Kenya.
AB  - In Kenya, sexually transmitted infections (STIs) such as Chlamydia trachomatis,
      Neisseria gonorrhoea, HIV, herpes simplex virus type 2 (HSV-2), syphilis and
      trichomoniasis tend to be prevalent, especially in women. Further, the research
      shows that women who test positive for STIs (other than HIV), have little
      knowledge of these infections. Of particular concern, is that there has been
      little attention on the part of government to educate the general public about
      STIs, yet these diseases can have devastating consequences on women's and men's
      health. In women, STIs can produce sequelae such as tubal infertility. To help
      reduce female factor infertility, the Kenya government should conduct a
      nationwide campaign to educate the public about the importance of screening and
      treatment of STIs.

PMID- 29209489
TI  - Primary umbilical endometriosis: a case report.
AB  - Primary umbilical endometriosis is a rare phenomenon accounting for 0,4-1,0% of
      extragenital endometriosis. Despite the fact that it mostly presents as a typical
      cyclic umbilical discharge coincidental with a palpable mass, the diagnosis is
      often delayed due to its low prevalence, as was seen in the presented case. The
      exact pathogenesis is still unclear. The golden standard for diagnosis is
      histopathological examination, but diagnostic tools like ultrasound, MRI or CT
      scan can be helpful. The differential diagnosis includes a wide range of
      disorders. Surgical management is the preferred treatment.

PMID- 29209490
TI  - The importance of recognizing paraneoplastic symptoms: a case report of
      Neuroendocrine Small Cell Carcinoma of the Endometrium presenting as
      Paraneoplastic Cushing's Syndrome.
AB  - This is the second well documented case of paraneoplastic Cushing's syndrome
      arising from a small cell carcinoma of the endometrium described in English
      literature. This tumour has an aggressive biological behaviour and early
      detection provides the only opportunity for long-term survival. In that regard
      recognition of associated paraneo- plastic features might be helpful.

PMID- 29209491
TI  - A 3D-Printed Sensor for Monitoring Biosignals in Small Animals.
AB  - Although additive manufacturing technologies, also known as 3D printing, were
      first introduced in the 1980s, they have recently gained remarkable popularity
      owing to decreased costs. 3D printing has already emerged as a viable technology
      in many industries; in particular, it is a good replacement for microfabrication
      technology. Microfabrication technology usually requires expensive clean room
      equipment and skilled engineers; however, 3D printing can reduce both cost and
      time dramatically. Although 3D printing technology has started to emerge into
      microfabrication manufacturing and medical applications, it is typically limited
      to creating mechanical structures such as hip prosthesis or dental implants.
      There have been increased interests in wearable devices and the critical part of
      such wearable devices is the sensing part to detect biosignals noninvasively. In
      this paper, we have built a 3D-printed sensor that can measure
      electroencephalogram and electrocardiogram from zebrafish. Despite measuring
      biosignals noninvasively from zebrafish has been known to be difficult due to
      that it is an underwater creature, we were able to successfully obtain
      electrophysiological information using the 3D-printed sensor. This 3D printing
      technique can accelerate the development of simple noninvasive sensors using
      affordable equipment and provide an economical solution to physiologists who are
      unfamiliar with complicated microfabrication techniques.

PMID- 29209492
TI  - Aquilegia B gene homologs promote petaloidy of the sepals and maintenance of the
      C domain boundary.
AB  - The model Aquilegia coerulea x "Origami" possesses several interesting floral
      features, including petaloid sepals that are morphologically distinct from the
      true petals and a broad domain containing many whorls of stamens. We undertook
      the current study in an effort to understand the former trait, but additionally
      uncovered data that inform on the latter. The Aquilegia B gene homolog AqPI is
      shown to contribute to the production of anthocyanin in the first whorl sepals,
      although it has no major role in their morphology. Surprisingly, knockdown of
      AqPI in Aquilegia coerulea x "Origami" also reveals a role for the B class genes
      in maintaining the expression of the C gene homolog AqAG1 in the outer whorls of
      stamens. These findings suggest that the transference of pollinator function to
      the first whorl sepals included a non-homeotic recruitment of the B class genes
      to promote aspects of petaloidy. They also confirm results in several other
      Ranunculales that have revealed an unexpected regulatory connection between the B
      and C class genes.

PMID- 29209493
TI  - Comparison of atopy patch testing to skin prick testing for diagnosing mite
      induced atopic dermatitis: a systematic review and meta-analysis.
AB  - Background: Atopic dermatitis (AD) can occur after contact with aeroallergens
      like house dust mites, pollen, and animal dander. Despite its controversial
      diagnostic value, the atopy patch test (APT) has been used as an important tool
      in the diagnosis of AD caused by house dust mites. Here, we present a meta
      analysis comparing APT to the common skin prick test (SPT) in the diagnosis of
      mite-induced AD. Methods: A structured search was performed using online
      databases and bibliographies published as of April 30, 2017. All studies
      evaluating the accuracy of APT and SPT in the diagnosis of mite-induced atopic
      eczema/dermatitis syndrome were selected, appraised, and data was extracted.
      Results: Ten studies were identified for inclusion in our analysis. Meta-analysis
      revealed that the pooled sensitivity, specificity, positive likelihood ratio,
      negative likelihood ratio, and diagnostic odds ratios for APT were 0.54 (95% CI
      0.42-0.66), 0.72 (95% CI 0.56-0.85), 1.97 (95% CI 1.20-3.23), 0.63 (95% CI 0.48
      0.83), and 3.12 (95% CI 1.53-6.39). The area under the summary receiver operating
      characteristic curve was 0.65 (95% CI 0.61-0.69). Conclusions: Our analysis
      indicates that APT is a useful tool in the screening of mite-induced AD, although
      this conclusion must be interpreted cautiously due to high heterogeneity among
      the included studies.

PMID- 29209494
TI  - RNAi mechanisms in Huntington's disease therapy: siRNA versus shRNA.
AB  - Huntington's Disease (HD) is a genetically dominant trinucleotide repeat disorder
      resulting from CAG repeats within the Huntingtin (HTT) gene exceeding a normal
      range (> 36 CAGs). Symptoms of the disease manifest in middle age and include
      chorea, dystonia, and cognitive decline. Typical latency from diagnosis to death
      is 20 years. There are currently no disease-modifying therapies available to HD
      patients. RNAi is a potentially curative therapy for HD. A popular line of
      research employs siRNA or antisense oligonucleotides (ASO) to knock down mutant
      Huntingtin mRNA (mHTT). Unfortunately, this modality requires repeated dosing,
      commonly exhibit off target effects (OTEs), and exert renal and hepatic toxicity.
      In contrast, a single AAV-mediated short-hairpin RNA (shRNA) dose can last years
      with low toxicity. In addition, we highlight research indicating that shRNA
      elicits fewer OTEs than siRNA when tested head-to-head. Despite this promise,
      shRNA therapy has been held back by difficulties controlling expression
      (oversaturating cells with toxic levels of RNA construct). In this review, we
      compare RNAi modalities for HD and propose novel methods of optimizing shRNA
      expression and on-target fidelity.

PMID- 29209495
TI  - Effect of neuroactive nutritional supplementation on body weight and composition
      in growing puppies.
AB  - Nutritional factors can dramatically affect development of young animals during
      the early stage of life. The objective of the present study was to examine the
      effects of a neuroactive nutritional supplement (NNS) containing DHA, taurine,
      carotenoids and vitamins on the body weight and body composition of growing
      puppies. A total of twenty-four 2-month-old Beagles were fed a nutritionally
      complete and balanced base diet and a control supplement daily during an initial
      1-month baseline assessment, after which they were divided into control and
      treatment groups. They were fed daily either control or treatment supplements in
      addition to the base diet from 3 to 12 months of age. Lean body mass and fat mass
      were assessed using quantitative magnetic resonance scans at 0 (baseline), 3, 6
      and 9 months of treatment. Total body weight and lean body mass did not differ
      between groups over time. The puppies in the treatment group showed a trend of
      reduced fat gain compared with those in the control group, and with a marginally
      significant difference at 6 months (P = 0.05). At 3 months, insulin-like growth
      factor 1 was higher (P = 0.02) in the treatment group compared with the control
      group. At 9 months, fasting lipid levels were lower (P < 0.05) and fat-oxidation
      metabolite 3-hydroxybutyrate was higher (P < 0.05) in the treatment group
      compared with the control group. These results may indicate that NNS has an
      impact on puppy growth and development, possibly by promoting fat metabolism;
      further investigation would be necessary to determine the full impact of this
      supplement on growth and development.

PMID- 29209496
TI  - Abnormal carbohydrate metabolism in a canine model for muscular dystrophy.
AB  - The canine golden retriever muscular dystrophy (GRMD) model is the best animal
      model for studying Duchenne muscular dystrophy in humans. Considering the
      importance of glucose metabolism in the muscles, the existence of metabolic and
      endocrine alterations in a wide range of muscular dystrophies, and the pre
      existing relationship between blood insulin concentration and muscular atrophy,
      the present study aimed to evaluate the postprandial glucose and insulin response
      in GRMD dogs. A total of eighteen golden retriever dogs were randomly distributed
      into three experimental groups: healthy/control (G1), female GRMD carriers (G2),
      and male dogs affected by GRMD (G3). Higher plasma resting glucose levels (P =
      0.0047) were seen in G2 and G3 compared with G1, as was the case for minimum (P =
      <0.0001), mean (P = 0.0002) and maximum (P = 0.0359) glucose values for G3
      compared with G1. Fructosamine concentrations were in accordance with reference
      values found in the literature for dogs. Insulin levels were lower in G3 compared
      with G1 (P = 0.0065); however, there was no evidence of insulin resistance
      according to the homeostasis model assessment index values obtained. As for the
      evaluation of postprandial responses, fluctuations of glucose (P = 0.0007) and
      insulin (P = 0.0149) were observed in G1 and G2, while in G3 the values remained
      constant. The results allowed us to identify metabolic changes related to
      carbohydrate metabolism in GRMD dogs, highlighting the importance of adequate
      food management for these animals.

PMID- 29209497
TI  - Long-chain n-3 PUFA in vegetarian women: a metabolic perspective.
AB  - Vegetarian diets have been associated with health benefits, but paradoxically are
      low in EPA and DHA which are important for development, particularly of the
      central nervous system, and for health. Humans have limited capacity for
      synthesis of EPA and DHA from alpha-linolenic acid, although this is greater in
      women than men. Oily fish and, to a lesser extent, dairy foods and meat are the
      primary sources of EPA and DHA in the diet. Exclusion of these foods from the
      diet by vegetarians is associated consistently with lower EPA and DHA status in
      vegetarian women compared with omnivores. The purpose of the present review was
      to assess the impact of low EPA and DHA status in vegetarian pregnancies on the
      development and health of children. EPA and DHA status was lower in breast milk
      and in infants of vegetarian mothers than those born to omnivore mothers, which
      suggests that in the absence of pre-formed dietary EPA and DHA, synthesis from
      alpha-linolenic acid is an important process in determining maternal EPA and DHA
      status in pregnancy. However, there have been no studies that have investigated
      the effect of low maternal DHA status in vegetarians on cognitive function in
      children. It is important to address this gap in knowledge in order to be
      confident that vegetarian and vegan diets during pregnancy are safe in the
      context of child development.

PMID- 29209498
TI  - Intensifying poultry production systems and the emergence of avian influenza in
      China: a 'One Health/Ecohealth' epitome.
AB  - Several kinds of pressure can lead to the emergence of infectious diseases. In
      the case of zoonoses emerging from livestock, one of the most significant changes
      that has taken place since the mid twentieth century is what has been termed the
      "livestock revolution", whereby the stock of food animals, their productivity and
      their trade has increased rapidly to feed rising and increasingly wealthy and
      urbanized populations. Further increases are projected in the future in low and
      middle-income countries. Using avian influenza as an example, we discuss how the
      emergence of avian influenza H5N1 and H7N9 in China was linked to rapid
      intensification of the poultry sector taking place in landscapes rich in wetland
      agriculture and wild waterfowls habitats, providing an extensive interface with
      the wild reservoir of avian influenza viruses. Trade networks and live-poultry
      markets further exacerbated the spread and persistence of avian influenza as well
      as human exposure. However, as the history of emergence of highly pathogenic
      avian influenza (HPAI) demonstrates in high-income countries such as the USA,
      Canada, Australia, the United Kingdom or the Netherlands, this is by no way
      specific to low and middle-income countries. Many HPAI emergence events took
      place in countries with generally good biosecurity standards, and the majority of
      these in regions hosting intensive poultry production systems. Emerging zoonoses
      are only one of a number of externalities of intensive livestock production
      systems, alongside antimicrobial consumption, disruption of nutrient cycles and
      greenhouse gases emissions, with direct or indirect impacts on human health. In
      parallel, livestock production is essential to nutrition and livelihoods in many
      low-income countries. Deindustrialization of the most intensive production
      systems in high-income countries and sustainable intensifications in low-income
      countries may converge to a situation where the nutritional and livelihood
      benefits of livestock production would be less overshadowed by its negative
      impacts on human an ecosystem health.

PMID- 29209499
TI  - Nasal Muco-ciliary transport time alteration: efficacy of 18 B Glycyrrhetinic
      acid.
AB  - Background: Mucociliary clearance is the main self-clearing system of the nasal
      cavity and paranasal sinuses.This is a very important means of non specific
      defence against continuous organic and inorganic contamination conveyed by air.
      It works by trapping particles and microorganisms in the mucus and then by
      transporting the mucous film to the pharynx where it is eliminated with a cough
      or swallowed. Its congenital or acquired abnormalities are involved in the
      occurrence of widespread infectious and often severe nose and paranasal sinuses
      diseases; generally concerning the rhinopharyngealtubal district.Restoring
      mucociliary clearance of the nasal epithelium when altered thus represents a key
      therapeutic tool against rhinosinus chronic diseases.This study evaluates the
      clinical efficacy of the inhalation of a natural compound (Narivent(r) nasal
      spray) in chronic vasomotor rhinitis. Methods: The study involved 79 patients
      suffering from chronic vasomotor rhinitis presenting an increased mucociliary
      clearance time. Patients were randomized into 2 groups: a first group of 49
      subjects and a second group of 30 subjects.The first group was treated with a
      nasal spray (Narivent(r) nasal spray) (2 sprays per nostril twice a day) for 30
      days.The second group was treated with a nasal spray containing isotonic solution
      in the same way and for the same period of the first group.Nasal Mucociliary
      transport time was measured in the patients of both groups before treatment,
      after 15 days of treatment, and at the end of the 30 days treatment. Results: The
      study shows how one of the treatments carried out determines a major objective
      reduction of the mucociliary clearance time in the patients under examination,
      using the method which involves the use of an insoluble coloured tracer
      (vegetable carbon), bringing the values back within normal range. At the end of
      the study we objectivated an increase in the rate of mucociliary transport in
      97.9% percentage of patients we enrolled. Conclusions: This study shows the
      effectiveness of treatment with natural extracts with nasal mucosa restoring
      function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory
      disease characterized by morphological and functional alteration of the normal
      nasal mucosa.

PMID- 29209500
TI  - Examining a staging model for anorexia nervosa: empirical exploration of a four
      stage model of severity.
AB  - Background: An illness staging model for anorexia nervosa (AN) has received
      increasing attention, but assessing the merits of this concept is dependent on
      empirically examining a model in clinical samples. Building on preliminary
      findings regarding the reliability and validity of the Clinician Administered
      Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores
      operationalising CASIAN severity scores into stages and assesses their
      relationship with other clinical features. Method: In women with DSM-IV-R AN and
      sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve
      (ROC) analysis (n = 67) assessed the relationship between the sensitivity and
      specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc
      adjusted residual analysis provided a preliminary assessment of the validity of
      the stages comparing the relationship between stage and treatment intensity and
      AN sub-types, and explored movement between stages after six months (Time 3) in a
      larger cohort (n = 171). Results: The CASIAN significantly distinguished between
      milder stages of illness (Stage 1 and 2) versus more severe stages of illness
      (Stages 3 and 4), and approached statistical significance in distinguishing each
      of the four stages from one other. CASIAN Stages were significantly associated
      with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was
      significantly associated with Stage at 6 month follow-up. Conclusions:
      Provisional support is provided for a staging model in AN. Larger studies with
      longer follow-up of cases are now needed to replicate and extend these findings
      and evaluate the overall utility of staging as well as optimal staging models.

PMID- 29209501
TI  - Association among self-compassion, childhood invalidation, and borderline
      personality disorder symptomatology in a Singaporean sample.
AB  - Background: Linehan's biosocial theory posits that parental invalidation during
      childhood plays a role in the development of borderline personality disorder
      symptoms later in life. However, little research has examined components of the
      biosocial model in an Asian context, and variables that may influence the
      relationship between childhood invalidation and borderline symptoms. Self
      compassion is increasingly regarded as an adaptive way to regulate one's emotions
      and to relate to oneself, and may serve to moderate the association between
      invalidation and borderline symptoms. The present study investigated the
      association among childhood invalidation, self-compassion, and borderline
      personality disorder symptoms in a sample of Singaporean undergraduate students.
      Methods: Two hundred and ninety undergraduate students from a large Singaporean
      university were recruited and completed measures assessing childhood
      invalidation, self-compassion, and borderline personality disorder symptoms.
      Results: Analyses using multiple regression indicated that both childhood
      invalidation and self-compassion significantly predicted borderline personality
      disorder symptomatology. Results from moderation analyses indicated that
      relationship between childhood invalidation and borderline personality disorder
      symptomatology did not vary as a function of self-compassion. Conclusion: This
      study provides evidence in support of aspects of the biosocial model in an Asian
      context, and demonstrates a strong association between self-compassion and
      borderline personality disorder symptoms, independent of one's history of
      parental invalidation during childhood.

PMID- 29209502
TI  - Monitoring diaphragm function in a patient with myasthenia gravis: electrical
      activity of the diaphragm vs. maximal inspiratory pressure.
AB  - Background: Maximal inspiratory pressure (MIP) is used to assess respiratory
      muscle strength of patients with myasthenia gravis (MG) requiring ventilatory
      support. Electrical activity of the diaphragm (E-di) has been used to guide
      weaning. Case presentation: The MIP and tidal volume/DeltaE-di (the patient-to
      ventilator breath contribution) were monitored in a 12-year-old girl with MG
      requiring ventilator support. The same ventilatory settings were maintained until
      extubation. During weaning, MIP increased slightly, but varied unpredictably.
      Tidal volume/DeltaE-di decreased at a constant rate as muscle strength recovered.
      Conclusion: In this patient with muscle weakness, E-di was a reliable tool to
      monitor weaning from mechanical ventilation.

PMID- 29209503
TI  - A comparative cross-sectional study of some hematological parameters of
      hypertensive and normotensive individuals at the university of Gondar hospital,
      Northwest Ethiopia.
AB  - Background: Hypertension is a major health problem worldwide. It can lead to
      cardiovascular disease and also leads to functional disturbances including
      hematological parameters. The abnormalities of haematological parameters may
      enhance an end-organ damage. Therefore, the aim of this study was to assess some
      hematological parameters of hypertensive individuals in comparison with
      normotensive individuals at University of Gondar hospital, northwest Ethiopia.
      Methods: A cross sectional comparative study was conducted from October to
      November 2015 on a total of 126 hypertensive and 126 normotensive individuals at
      University of Gondar Hospital. All participants after taking informed consent
      were interviewed for detailed history and 3 ml of blood was collected for
      hematological test analysis. Independent t-test and the Mann Whitney u-test were
      used to find out significant difference and Pearson's and Spearman's correlation
      were used for correlation test. P values less than 0.05 was considered the level
      of significance. Result: From a total of 252 study subjects, about 67.5% were
      females. The mean age of study subjects was 50.3 +/- 11 years for hypertensive
      individuals and 49.8 +/- 11.6 years for normotensive individuals with range of 18
      65 years. In the present study, the median (IQR) value of WBC, RBC, Hgb, HCT, MCV
      and the mean value of MCHC, RDW, MPV and PDW were significantly higher in
      hypertensive group compared to apparently healthy normotensive groups.
      Additionally, WBC, RBC, Hgb, HCT and PLT showed statistically significant
      positive correlations with blood pressure indices. Platelet count and MCH did not
      show statistically significant difference between the two groups. Conclusion:
      Hypertension has impact on hematological parameters. In this study, the mean and
      median values of haematological parameters in hypertensive individuals were
      significantly different compared to apparently healthy normotensive individuals.
      Hence, hematological parameters can be used to monitor the prognosis of the
      disease and manage hypertensive related complications, and it is important to
      assess hematological parameters for hypertensive individuals which may help to
      prevent complications associated hematological disorders.

PMID- 29209504
TI  - The FIFA 11+ injury prevention program for soccer players: a systematic review.
AB  - Background: Soccer is one of the most widely played sports in the world. However,
      soccer players have an increased risk of lower limb injury. These injuries may be
      caused by both modifiable and non-modifiable factors, justifying the adoption of
      an injury prevention program such as the Federation Internationale de Football
      Association (FIFA) 11+. The purpose of this study was to evaluate the efficacy of
      the FIFA 11+ injury prevention program for soccer players. Methodology: This meta
      analysis was based on the PRISMA 2015 protocol. A search using the keywords
      "FIFA," "injury prevention," and "football" found 183 articles in the PubMed,
      MEDLINE, LILACS, SciELO, and ScienceDirect databases. Of these, 6 studies were
      selected, all of which were randomized clinical trials. Results: The sample
      consisted of 6,344 players, comprising 3,307 (52%) in the intervention group and
      3,037 (48%) in the control group. The FIFA 11+ program reduced injuries in soccer
      players by 30%, with an estimated relative risk of 0.70 (95% confidence interval,
      0.52-0.93, p = 0.01). In the intervention group, 779 (24%) players had injuries,
      while in the control group, 1,219 (40%) players had injuries. However, this
      pattern was not homogeneous throughout the studies because of clinical and
      methodological differences in the samples. This study showed no publication bias.
      Conclusion: The FIFA 11+ warm-up program reduced the risk of injury in soccer
      players by 30%.

PMID- 29209505
TI  - Evaluation of environmental heat stress on physiological parameters.
AB  - Background: Thermal component of the atmospheric environment is an important
      issue which is related to human's health. Thermal environment includes both heat
      exchange conditions (stress) and the physiological response (strain). The aim of
      this study was to measure the association of heat indices (PSI, HSI, Humidex)
      especially subjective one (STI) with some physiological parameters (Blood
      pressure, pulse rate and skin temperature). Methods: This is a cross-sectional
      study conducted on 387 male farmers on Boukan, West Azerbaijan, Iran in 2016.
      Sampling was conducted on the hottest days in summer on July based on the
      meteorological report. Heat parameters was measured 3 times in each session.
      Results: Direct associations were found between heat indices and physiological
      parameters except systolic BP. However, invers associations were found between
      blood pressure, skin and core body temperature, pulse rate with all heat indices.
      Based on the results of linear regression analysis, significant association was
      found between WBGT and skin temperature (B = 0.31, CI: 0.02, 0.61, P = 0.03).
      Results also showed significant association between Humidex and skin temperature
      (B = 0.21, CI: -0.03, 0.40, P = 0.02). However, no significant associations were
      found between other heat stress indices including UTCI, PHS, HIS, STI and Humidex
      with all study physiological parameters (core body temperature, systolic and
      diastolic blood pressure and also pulse rate). Conclusion: As expected, farmer's
      health is affected by physiological parameters. Moreover, among assessed types of
      heat stress indices WBGT and Humidex were more powerful to show better the
      association with mentioned physiological parameters.

PMID- 29209506
TI  - Border Terriers under primary veterinary care in England: demography and
      disorders.
AB  - Background: The Border Terrier is a working terrier type that is generally
      considered to be a relatively healthy and hardy breed. This study aimed to
      characterise the demography and common disorders of Border Terriers receiving
      veterinary care in England using de-identified electronic patient record data
      within the VetCompassTM Programme. Results: Annual birth proportion for Border
      Terriers showed a decreasing trend from 1.46% in 2005 to 0.78% in 2014. The
      median adult bodyweight for males (10.9 kg, IQR: 9.6-12.3, range: 6.3-25.0) was
      higher than for females (9.1 kg, IQR: 8.2-10.3, range: 5.2-21.6) (P < 0.001). The
      median longevity was 12.7 years (IQR 9.3-14.3, range 1.0-17.5).The most prevalent
      fine-level disorders recorded were periodontal disease (17.63%, 95% CI: 15.62
      19.79), overweight/obesity (7.01%, 95% CI: 5.69-8.52) and otitis externa (6.71%,
      95% CI: 5.42-8.19). The most prevalent grouped-level precision disorders were
      dental disorder (18.54%, 95% CI: 16.48-20.74), enteropathy (11.68%, 95% CI: 10.00
      13.53), and skin disorder (10.17%, 95% CI: 8.60-11.93).Syndromic analysis showed
      that the most prevalent body locations affected were the head-and-neck (37.75%,
      95% CI: 35.14-40.43), abdomen (18.61%, 95% CI: 16.55-20.81) and limb (11.53%, 95%
      CI: 9.86-13.37). At least one organ system was affected in 834 (62.85%) Border
      Terriers. The most prevalent organ systems affected were the digestive (32.03%,
      95% CI: 29.52-34.61), integument (26.68%, 95% CI: 24.31-29.14), connective/soft
      tissue (11.15%, 95% CI: 9.51-12.97) and auditory (9.87%, 95% CI: 8.32-11.60). At
      least one affected pathophysiological process was described in 881 (66.39%)
      Border Terriers. The most prevalent pathophysiologic processes recorded were
      inflammation (31.65%, 95% CI: 29.15-34.23), nutritional (9.04%, 95% CI: 7.55
      10.72), mass/swelling (8.89%, 95% CI: 7.42-10.55), traumatic (7.99%, 95% CI: 6.59
      9.58) and infectious (7.76%, 95% CI: 6.38-9.33). Conclusions: This study
      documented a trend towards reducing ownership and relatively long-livedness in
      the Border Terrier. The most common disorders were periodontal disease,
      overweight/obesity and otitis externa. Predisposition to dental and neurological
      disease was suggested. These results can provide a comprehensive evidence
      resource to support breed-based health plans that can contribute positively to
      reforms to improve health and welfare within the breed.

PMID- 29209507
TI  - Routinely collected health data to study inherited heart disease: a systematic
      review (2000-2016).
AB  - Objective: Our understanding of inherited heart disease is predominantly based on
      retrospective specialised clinic cohorts, which have inherent selection bias.
      Population-based routinely collected data can provide insight into unbiased,
      large-scale patterns of treatment and care but may be limited by the granularity
      of clinical information available. We sought to synthesise the global literature
      to determine whether we can identify patients with inherited heart diseases using
      routinely collected health data. Methods: Medline, Embase, CINAHL, PreMEDLINE and
      Google Scholar citation databases were searched for relevant articles published
      between 1 January 2000 and 31 October 2016. Results: A total of 5641
      titles/abstracts were screened and 46 full-text articles were retrieved. Twelve
      peer-reviewed, English-language manuscripts met our inclusion criteria. Studies
      predominantly focused on Marfan syndrome (41%) or hypertrophic cardiomyopathy
      (29%). All studies used International Classification of Disease diagnosis codes
      to define inherited heart disease populations; three studies also used procedure
      codes. Nine of the 17 definitions for inherited heart disease were repeated
      across studies. Conclusions: Inherited heart disease populations can be
      identified using routinely collected health data, though challenges relate to
      existing diagnosis codes. This is an underutilised resource with the potential to
      inform patterns of care, patient outcomes and overall disease burden.

PMID- 29209509
TI  - Realtime ultrasound guided percutaneous tracheostomy in emergency setting: the
      glass ceiling has been broken.
AB  - Background: In recent years ultrasound guided percutaneous tracheostomy (USPCT)
      has become a routine practice in critical care units. Its safety and superiority
      over conventional percutaneous tracheostomy and bronchoscopic guided PCT is
      proven to be non-inferior in elective cases. However its role in emergency
      percutaneous tracheostomy has never been studied, since percutaneous tracheostomy
      itself remains an enigma in accessing emergency airway. There is no report of use
      of ultrasound guided percutaneous tracheostomy in emergency setting so far in the
      literature. We report our early experience with USPCT in emergency setting.
      Methods: Sixteen adult patients who required access to an emergency surgical
      airway after failure to accomplish emergency oro-tracheal intubation were the
      study population. Their airway was accessed by USPCT. Recorded data included
      clinical and demographic data including time taken to perform the procedure and
      complications. Short term and long term follow ups for a period of 2 years were
      done for the survivors. Results: Twelve male and four female patients underwent
      the procedure and the average time of the procedure was 3.6 min with no failures
      nor conversions to surgical tracheostomy and no complications. The average oxygen
      saturation was 86% and average Glasgow coma scale was 8.4. This time period
      included the oxygen insufflation time. 10 patients were decannulated while six
      patients died due to the pathology of the disease itself. There were no
      complications in either short term or long term follow up. Conclusion: USPCT has
      a definitive role in emergency both in trauma and non-trauma setting. It is safe,
      feasible and faster in experienced hands. Use of USPCT in emergency setting has
      further narrowed the list of contraindications of percutaneous tracheostomy.

PMID- 29209508
TI  - Promoters from the itaconate cluster of Ustilago maydis are induced by nitrogen
      depletion.
AB  - Background: Ustilago maydis is known for its natural potential to produce a broad
      range of valuable chemicals, such as itaconate, from both industrial carbon waste
      streams and renewable biomass. Production of itaconate, and many other secondary
      metabolites, is induced by nitrogen limitation in U. maydis. The clustered genes
      responsible for itaconate production have recently been identified, enabling the
      development of new expression tools that are compatible with biotechnological
      processes. Results: Here we report on the investigation of two of the native
      promoters, P tad1 and P mtt1 , from the itaconate cluster of U. maydis MB215. For
      both promoters the specific activation upon nitrogen limitation, which is known
      to be the trigger for itaconate production in Ustilago, could be demonstrated by
      gfp expression. The promoters cover a broad range of expression levels,
      especially when combined with the possibility to create single- and multicopy
      construct integration events. In addition, these reporter constructs enable a
      functional characterization of gene induction patterns associated with itaconate
      production. Conclusions: The promoters are well suited to induce gene expression
      in response to nitrogen limitation, coupled to the itaconate production phase,
      which contributes towards the further improvement of organic acid production with
      Ustilago.

PMID- 29209510
TI  - Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study
      protocol, review of literature and survey of current practices.
AB  - Background: Congenital diaphragmatic hernia (CDH) is commonly associated with
      pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH
      PH) is frequently resistant to conventional pulmonary vasodilator therapy
      including inhaled nitric oxide (iNO) possibly due to right and left ventricular
      dysfunction. Milrinone is an intravenous inotrope and lusitrope with pulmonary
      vasodilator properties and has been shown anecdotally to improve oxygenation in
      PH. We developed this pilot study to determine if milrinone infusion would
      improve oxygenation in neonates >=36 weeks postmenstrual age (PMA) with CDH.
      Methods/design: Data on pulmonary vasodilator management and outcome of CDH
      patients was collected from 18 university NICUs affiliated with the Neonatal
      Research Network (NRN) from 2011 to 2012. The proposed pilot will be a masked,
      placebo-controlled, multicenter, randomized trial of 66 infants with CDH with an
      oxygenation index (OI) >=10 or oxygen saturation index (OSI) >=5. The primary
      outcome is the oxygenation response, as determined by change in OI at 24 h after
      initiation of study drug. As secondary outcomes, we will determine oxygenation at
      48 h and 72 h post-infusion, right ventricular pressures on echocardiogram and
      the incidence of systemic hypotension, arrhythmias, intracranial hemorrhage,
      survival without extracorporeal membrane oxygenation, and chronic lung disease
      (oxygen need at 28 days postnatal age). Finally, we will evaluate the pulmonary
      and nutritional status at 4, 8 and 12 months of age using a phone questionnaire.
      Results: Three hundred thirty-seven infants with CDH were admitted to NRN NICUs
      in 2011 and 2012 of which 275 were >=36 weeks PMA and were exposed to the
      following pulmonary vasodilators: iNO (39%), sildenafil (17%), milrinone (17%),
      inhaled epoprostenol (6%), intravenous epoprostenol (3%), and intravenous PGE1
      (1%). ECMO was required in 36% of patients. Survival to discharge was 71%.
      Discussion: CDH is an orphan disease with high mortality with few randomized
      trials evaluating postnatal management. Intravenous milrinone is a commonly used
      medication in neonatal/pediatric intensive care units and is currently used in
      17% of patients with CDH within the NRN. This pilot study will provide data and
      enable further studies evaluating pulmonary vasodilator therapy in CDH. Trial
      registration: ClinicalTrials.gov; NCT02951130; registered 14 October 2016.

PMID- 29209511
TI  - Effectiveness of composting as a biosecure disposal method for porcine epidemic
      diarrhea virus (PEDV)-infected pig carcasses.
AB  - Background: Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine
      that has emerged as a worldwide threat to swine herd health and production.
      Substantial research has been conducted to assess viability of the virus on
      surfaces of vehicles and equipment, in feed and water, and on production building
      surfaces, but little is known about the persistence in PEDV-infected carcasses
      and effective disposal methods thereof. This study was conducted to quantify the
      persistence of PEDV RNA via quantitative real-time reverse transcription
      polymerase chain reaction (qRT-PCR) at various time-temperature combinations and
      in infected piglet carcasses subjected to composting. Although this method does
      not distinguish between infectious and noninfectious virus, it is a rapid and
      sensitive test to evaluate materials for evidence of virus genome. Results: In
      the first study, PEDV was suspended in cell culture media at 1 * 105 TCID50 per
      sample (1 mL sample size) and subjected to various time and temperature
      combinations in triplicate including temperatures of 37, 45, 50, 55, 60, 65, 70 
      degrees C and exposure times of 0, 1, 2, 3, 4, 5, 7, and 14 days. At all
      temperatures, viral RNA copies declined over time, with the decline most marked
      and rapid at 65 and 70  degrees C. Detectable RNA did persist throughout the
      trial in all but the most extreme condition, where two of three samples incubated
      at 70  degrees C yielded undetectable viral RNA after 14 days. In the second
      study, PEDV-infected piglet carcasses were subjected to two cycles of composting
      lasting 36 and 37 days, respectively, for a total compost time of 73 days.
      Composting was performed in triplicate windrow sections housed inside biosecure,
      climate-controlled rooms using insulated bins designed to represent a continuous
      windrow compost pile. Temperatures reached 35-57  degrees C for 26 days of cycle
      1 and 35-45  degrees C for 3 days of cycle 2. Samples consisting of carbon
      material with or without decomposed tissue as available per sample site collected
      at ten locations throughout the cross-section of each windrow section following
      the primary and secondary compost cycles yielded no detectable viral RNA.
      Conclusions: Composting appears to be an effective disposal method for PEDV
      infected piglet carcasses under the conditions examined. The combination of time
      and high temperature of the compost cycle effectively degraded viral RNA in cell
      culture media that should provide optimum stability. Complex compost material
      matrices collected from windrow sections yielded undetectable PEDV RNA by qRT-PCR
      after one 36-day compost cycle despite incomplete decomposition of soft tissue.

PMID- 29209512
TI  - The ReSiT study (reducing sitting time): rationale and protocol for an
      exploratory pilot study of an intervention to reduce sitting time among office
      workers.
AB  - Background: Desk-based workers engage in long periods of uninterrupted sitting
      time, which has been associated with morbidity and premature mortality. Previous
      workplace intervention trials have demonstrated the potential of providing sit
      stand workstations, and of administering motivational behaviour change
      techniques, for reducing sitting time. Yet, few studies have combined these
      approaches or explored the acceptability of discrete sitting-reduction behaviour
      change strategies. This paper describes the rationale for a sitting-reduction
      intervention that combines sit-stand workstations with motivational techniques,
      and procedures for a pilot study to explore the acceptability of core
      intervention components among university office workers. Methods: The
      intervention is based on a theory and evidence-based analysis of why office
      workers sit, and how best to reduce sitting time. It seeks to enhance motivation
      and capability, as well as identify opportunities, required to reduce sitting
      time. Thirty office workers will participate in the pilot study. They will
      complete an initial awareness-raising monitoring and feedback task and
      subsequently receive a sit-stand workstation for a 12-week period. They will also
      select from a 'menu' of behaviour change techniques tailored to self-declared
      barriers to sitting reduction, effectively co-producing and personally tailoring
      their intervention. Interviews at 1, 6, and 12 weeks post-intervention will
      explore intervention acceptability. Discussion: To our knowledge, this will be
      the first study to explore direct feedback from office workers on the
      acceptability of discrete tailored sitting-reduction intervention components that
      they have received. Participants' choice of and reflections on intervention
      techniques will aid identification of strategies suitable for inclusion in the
      next iteration of the intervention, which will be delivered in a self
      administered format to minimise resource burden. Trial registration:
      ISRCTN29395780 (registered 21 November 2016).

PMID- 29209513
TI  - Can we predict necrosis intra-operatively? Real-time optical quantitative
      perfusion imaging in surgery: study protocol for a prospective, observational, in
      vivo pilot study.
AB  - Background: Compromised perfusion as a result of surgical intervention causes a
      reduction of oxygen and nutrients in tissue and therefore decreased tissue
      vitality. Quantitative imaging of tissue perfusion during reconstructive surgery,
      therefore, may reduce the incidence of complications. Non-invasive optical
      techniques allow real-time tissue imaging, with high resolution and high
      contrast. The objectives of this study are, first, to assess the feasibility and
      accuracy of optical coherence tomography (OCT), sidestream darkfield microscopy
      (SDF), laser speckle contrast imaging (LSCI), and fluorescence imaging (FI) for
      quantitative perfusion imaging and, second, to identify/search for criteria that
      enable risk prediction of necrosis during gastric tube and free flap
      reconstruction. Methods: This prospective, multicenter, observational in vivo
      pilot study will assess tissue perfusion using four optical technologies: OCT,
      SDF, LSCI, and FI in 40 patients: 20 patients who will undergo gastric tube
      reconstruction after esophagectomy and 20 patients who will undergo free flap
      surgery. Intra-operative images of gastric perfusion will be obtained directly
      after reconstruction at four perfusion areas. Feasibility of perfusion imaging
      will be analyzed per technique. Quantitative parameters directly related to
      perfusion will be scored per perfusion area, and differences between biologically
      good versus reduced perfusion will be tested statistically. Patient outcome will
      be correlated to images and perfusion parameters. Differences in perfusion
      parameters before and after a bolus of ephedrine will be tested for significance.
      Discussion: This study will identify quantitative perfusion-related parameters
      for an objective assessment of tissue perfusion during surgery. This will likely
      allow early risk stratification of necrosis development, which will aid in
      achieving a reduction of complications in gastric tube reconstruction and free
      flap transplantation. Trial registration: Clinicaltrials.gov registration number
      NCT02902549. Dutch Central Committee on Research Involving Human Subjects
      registration number NL52377.018.15.

PMID- 29209514
TI  - Fish oil supplementation in chronic obstructive pulmonary disease: feasibility of
      conducting a randomised controlled trial.
AB  - Background: Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) may act
      as an effective adjunct therapy for chronic obstructive pulmonary disease (COPD),
      a condition characterised by persistent airflow limitation and inflammation.
      However, the nature of this illness presents challenges for evaluating potential
      benefits. The aim of this study was to determine the feasibility of undertaking a
      randomised controlled trial of LCn-3PUFA supplementation in adults with COPD.
      Methods: A 16-week parallel, double-blind, randomised, placebo-controlled dietary
      supplementation trial was conducted. Participants diagnosed with COPD were
      randomly allocated to take six 1-g capsules of fish oil (3.6 g LCn-3PUFA) or corn
      oil (placebo) daily for 16 weeks. Key outcomes used to determine the feasibility
      of the trial included recruitment rate, participant retention rate and supplement
      adherence (blood biomarker and returned capsule count). An estimate of the effect
      size for clinical outcomes such as pulmonary function and functional exercise
      capacity was calculated. Results: None of the key feasibility criteria were met.
      The enrolment target was 40 participants in 52 weeks; however, only 13 were
      finally enrolled, with just seven in the first 52 weeks. Eight participants
      completed the study (retention rate 62%). Targets for compliance were not
      achieved; red blood cell LCn-3PUFA content (expressed as percentage of total
      fatty acids) did not increase by more than 2% in the fish oil group; capsule
      counts were unreliable. As the target sample size was not achieved and only a
      small number of participants completed the study, it was not possible to use the
      variance in clinical outcomes to estimate a sample size for a future study.
      Conclusions: This study highlights major difficulties, especially with
      recruitment, in conducting this LCn-3PUFA supplementation trial in people with
      COPD, rendering the protocol unfeasible by predetermined criteria. A modified
      approach is needed to investigate potential health benefits of fish oil in people
      with COPD. A multicentre study with changes to inclusion and exclusion criteria
      is recommended. Trial registration: Australia and New Zealand Clinical Trials
      Register (ANZCTR), ACTRN12612000158864.

PMID- 29209516
TI  - Subretinal fluid application to close a refractory full thickness macular hole.
AB  - Background: To close a refractory full thickness macular hole (FTMH) by adjacent
      subretinal fluid application to release the elastic retina from the retinal
      pigment epithelium (RPE). Case presentation: A 83 years old patient presented an
      old FTMH with a diameter of 1444 MUm. After confirming intraoperatively the
      complete release of the epiretinal membrane around the FTMH, we installed 3 small
      subretinal blebs around the hole, to release the adjacent retina from the RPE.
      The mobilized retina was gently moved towards the macular center. A silicone oil
      tamponade was installed to secure a proper healing and observation of the FTMH.
      The closure of the 1444 MUm FTMH was seen on indirect ophthalmoscopy and
      confirmed by OCT 5 days after surgery by restoring the retinal architecture. A
      late reopening was not apparent at the postoperative observations. Visual acuity
      improved from hand motion to 20/200 at 4 weeks postoperative. Conclusion:
      Although FTMH develop by epiretinal tangential traction, large FTMH may persist
      even after complete release of its epiretinal traction. Subretinal fluid
      application may release the flexible retina from the RPE to achieve a relocation
      at the central fovea facilitating an anatomical closure of the macular hole.

PMID- 29209515
TI  - Ketogenic diets as an adjuvant therapy in glioblastoma (the KEATING trial): study
      protocol for a randomised pilot study.
AB  - Background: Glioblastoma is the commonest form of malignant brain tumour in
      adults, affecting 2-3 people per 100,000 per year. Despite current treatment
      options including surgical resection, radiotherapy and temozolomide chemotherapy,
      overall survival at 2 years is approximately 27%, with a median survival of 12-14
      months. The ketogenic diet (KD) is postulated to work by simulating the metabolic
      response to fasting by promoting the utilisation of ketones as a primary energy
      source, and depriving the glycolytic pathways utilised by malignant glioma cells
      for growth. At present, there is no consensus as to which KD is preferable, with
      previous case series using different KDs, at different points in the treatment
      pathway. The aim of this randomised pilot study is to investigate protocol
      feasibility, tolerability and the impact on patient health and quality of life of
      two different KDs within an NHS setting. The results of this pilot study will
      inform which KD will be most deliverable and adhered to by patients in order to
      test for effectiveness in future trials. Methods: A prospective, non-blinded,
      randomised, pilot study will be undertaken in 12 patients with newly diagnosed
      glioblastoma treated by surgical resection. Patients will be randomised in a
      ratio of 1:1, using a permuted block randomisation method to one of two diets;
      the modified ketogenic diet and the medium chain triglyceride ketogenic diet.
      Primary data collection will take place 12 weeks after starting the diet and
      secondary data collection after 12 months. Feasibility will be assessed by
      retention and recruitment rates, ability to enrol patients prior to starting
      chemoradiotherapy, dietary compliance and adjustments, ketone levels, glucose
      levels and intervention time. Patient impact will be assessed through quality of
      life and food acceptability questionnaires, gastrointestinal side effects and
      changes to biochemical markers and anthropometric measures, assessed at regular
      intervals. Discussion: The results of this pilot study will be used to inform the
      feasibility, methodological design and power calculations of future phase III
      clinical trials investigating the effectiveness of KD as an adjuvant therapy in
      the management of glioblastoma. Trial registration: ISRCTN71665562 and
      NCT03075514.

PMID- 29209517
TI  - Clinical course and recommendations for patients after anterior cruciate ligament
      injury and subsequent reconstruction: A narrative review.
AB  - Almost all athletes who have suffered an anterior cruciate ligament (ACL) injury
      expect a full return to sports at the same pre-injury level after ACL
      reconstruction (ACLR). Detailed patient information on the reasonable outcomes of
      the surgery may be essential to improve patient satisfaction.Pre-operative
      rehabilitation before ACLR should be considered as an addition to the standard of
      care to maximise functional outcomes after ACLR.We propose an optimised criterion
      based rehabilitation programme within a biopsychosocial framework.No benchmark
      exists for evaluating return-to-sport (RTS) readiness after ACLR. Therefore, the
      authors propose a multi-factorial RTS test battery. A combination of both
      physical and psychological elements should be included in the RTS test
      battery.There is need for shared decision-making regarding RTS. Cite this
      article: EFORT Open Rev 2017;2:410-420. DOI: 10.1302/2058-5241.2.170011.

PMID- 29209519
TI  - The surgical treatment of acromioclavicular joint injuries.
AB  - Acromioclavicular joint (ACJ) injuries are common, but their incidence is
      probably underestimated. As the treatment of some sub-types is still debated, we
      reviewed the available literature to obtain an overview of current management.We
      analysed the literature using the PubMed search engine.There is consensus on the
      treatment of Rockwood type I and type II lesions and for high-grade injuries of
      types IV, V and VI. The treatment of type III injuries remains controversial, as
      none of the studies has proven a significant benefit of one procedure when
      compared with another.Several approaches can be considered in reaching a valid
      solution for treating ACJ lesions. The final outcome is affected by both vertical
      and horizontal post-operative ACJ stability. Synthetic devices, positioned using
      early open or arthroscopic procedures, are the main choice for young people.Type
      III injuries should be managed surgically only in cases with high-demand sporting
      or working activities. Cite this article: EFORT Open Rev 2017;2:432-437. DOI:
      10.1302/2058-5241.2.160085.

PMID- 29209518
TI  - Diagnosis and treatment of soft-tissue sarcomas of the extremities and trunk.
AB  - The relatively low incidence and often atypical clinical presentation of soft
      tissue sarcomas (STS) impedes early and adequate diagnosis. Patients may report
      on recently enlarged soft-tissue swellings, infrequently complain of painful
      lesions, or even have no symptoms at all.A thorough diagnostic work-up is
      essential in order to distinguish between benign soft-tissue tumours and STSs.
      Patient history, clinical features and radiological findings all help in
      assessing the underlying pathology. 'Worrying' features such as recent increase
      in size, deep location relative to the fascia, a tumour exceeding 4 cm in size,
      and invasive growth patterns seen on imaging should prompt verification by
      biopsy.Even though acquisition of biopsy material may be incomplete, one should
      bear in mind some essential rules. Regardless of the biopsy technique applied,
      the most direct route to the lump in question should be identified, contamination
      of adjacent structures should be avoided and a sufficient amount of tissue
      acquired.Treatment of STS is best planned by a multidisciplinary team, involving
      experts from various medical specialities. The benchmark therapy consists of en
      bloc resection of the tumour, covered by a safety margin of healthy tissue.
      Depending on tumour histology, grade, local extent and anatomical stage,
      radiotherapy, chemotherapy and isolated hyperthermic limb perfusion may be
      employed.Due to the complexity of treatment, any soft-tissue swelling suspected
      of malignancy is best referred directly to a sarcoma centre, where therapeutic
      management is carefully planned by an experienced multidisciplinary team. Cite
      this article: EFORT Open Rev 2017;2:421-431. DOI: 10.1302/2058-5241.2.170005.

PMID- 29209520
TI  - Comparing assessment frameworks for cancer drugs between Canada and Europe: What
      can we learn from the differences?
AB  - The increasing burden of costs associated with novel cancer therapies is becoming
      untenable. In Europe and Canada, assessment frameworks have been developed to
      attribute value to novel therapies and ultimately facilitate access to cancer
      drug funding. A review of the two frameworks has not previously been undertaken.
      This review provides insight into the relative strengths and benefits of each
      approach, the various perspectives of value (patient, physician and societal) and
      how the frameworks relate to their unique context and core principles. Both
      frameworks assess the clinical benefit of a new cancer therapy. The European
      framework considers effectiveness, quality of life, and toxicity in its
      determination of benefit and has the advantage of providing a simple summary
      score to facilitate priority setting. The Canadian framework considers other
      elements including cost-effectiveness, patient preferences and adoption
      feasibility; its deliberative framework precludes a simple summative presentation
      of value but can address complex and nuanced drug funding considerations with
      flexibility. Both frameworks have evolved to meet the needs unique to their
      jurisdictions and offer potentially complementary tools in the assessment of new
      cancer drugs. Lessons learnt in both systems can be applied to future iterations
      of the frameworks, which remain works in progress.

PMID- 29209521
TI  - Management of patients with end-stage renal disease undergoing chemotherapy:
      recommendations of the Associazione Italiana di Oncologia Medica (AIOM) and the
      Societa Italiana di Nefrologia (SIN).
AB  - Background: The overall risk of some cancers is increased in patients receiving
      regular dialysis treatment due to chronic oxidative stress, a weakened immune
      system and enhanced genomic damage. These patients could benefit from the same
      antineoplastic treatment delivered to patients with normal renal function, but a
      better risk/benefit ratio could be achieved by establishing specific guidelines.
      Key considerations are which chemotherapeutic agent to use, adjustment of dosages
      and timing of dialysis in relation to the administration of chemotherapy.
      Methods: We have reviewed available data present in the literature, including
      recommendations and expert opinions on cancer risk and use of chemotherapeutic
      agents in patients with end-stage renal disease. Experts selected by the boards
      of the societies provided additional information which helped greatly in
      clarifying some issues on which clear-cut information was missing or available
      data were conflicting. Results: Data on the optimal use of chemotherapeutic
      agents or on credible schemes of polychemotherapy in haemodialysed patients are
      sparse and mainly derive from case reports or small case series. However,
      recommendations on dosing and timing of dialysis can be proposed for the most
      prescribed chemotherapeutic agents. Discussion: The use of chemotherapeutic
      agents as single agents, or in combination, can be safely given in patients with
      end-stage renal disease. Appropriate dosage adjustments should be considered
      based on drug dialysability and pharmacokinetics. Coordinated care between
      oncologists, nephrologists and pharmacists is of pivotal importance to optimise
      drug delivery and timing of dialysis.

PMID- 29209522
TI  - Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging
      sequencing for new treatment targets.
AB  - Lung cancer is the leading cause of cancer-related deaths in the world. Immune
      checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against
      tumour cells. These agents are available for the treatment of non-small cell lung
      cancer (NSCLC) after failure of platinum-based therapy. One recent study has
      demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for
      first-line treatment. Nevertheless, this benefit was only for a minority of the
      population (30%) whose tumour programmed death receptor ligand-1 (PD-L1)
      expression was above 50%. Therefore, several strategies are under investigation.
      One option for patients with PD-L1 expression lower than 50% may be the
      combination of ICI with platinum-based chemotherapy or with ICIs against
      different targets. However, all of these combinations are at an early stage of
      investigation and may be very expensive or toxic, producing several harmful
      adverse events.

PMID- 29209523
TI  - Second-line treatments: moving towards an opportunity to improve survival in
      advanced gastric cancer?
AB  - Gastric cancer is the third leading cause of cancer-related death globally with
      approximately 723 000 deaths every year. Most patients present with advanced
      unresectable or metastatic disease, only amenable to palliative systemic
      treatment and a median survival uncommonly exceeding 12 months. Over the last
      years, the efficacy of chemotherapy combination has plateaued and the
      introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has
      resulted in a limited survival gain in the upfront setting. After this positive
      experience, first-line treatment with new targeted therapies failed to improve
      the outcome of advanced gastric cancer. On the contrary, second-line options,
      including monochemotherapy with taxanes or irinotecan and the anti-vascular
      endothelial growth factor receptor 2 ramucirumab, either alone or combined with
      paclitaxel, opened new therapeutic rooms for an ever-increasing number of
      patients who maintain an acceptable performance status across multiple lines.
      This article provides an updated overview on the current management of advanced
      gastric cancer and discusses how the different treatment options available may be
      best combined to favourably impact the outcome of patients following the logic of
      a treatment strategy.

PMID- 29209525
TI  - Final results of the large-scale multinational trial PROFILE 1005: efficacy and
      safety of crizotinib in previously treated patients with advanced/metastatic ALK
      positive non-small-cell lung cancer.
AB  - Purpose: Crizotinib is a potent, orally administered tyrosine kinase inhibitor
      approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced
      non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005,
      the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC.
      Patients and methods: PROFILE 1005 (NCT00932451) was a multicenter, single-arm
      phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg
      twice daily; 3 week continuous treatment cycles) in patients with ALK-positive
      NSCLC after failure of >=1 lines of systemic treatment for locally
      advanced/metastatic disease. Patients' tumour ALK status was initially determined
      by a central laboratory until a protocol amendment permitted enrolment of
      patients based on locally determined ALK status. Co-primary endpoints were
      objective response rate (ORR), evaluated using Response Evaluation Criteria in
      Solid Tumours V.1.1 and adverse events (AEs). Cancer-specific patient-reported
      outcomes (PROs) were also assessed using the European Organisation for the
      Research and Treatment of Cancer QLQ-C30 and its lung cancer module QLQ-LC13.
      Results: 1069 patients were enrolled; 1066 received crizotinib. The as-treated
      population comprised 908 and 158 patients, in whom tumour positive ALK-status was
      determined centrally (+/- locally) or locally only, respectively. At baseline, a
      majority of patients were <65 years (84%), 66% were never smokers and 46% were
      Asian. Derived investigator-assessed ORR was 54% (95% CI 51 to 57) and 41% (95%
      CI 33 to 49) in the central-testing and local-testing subgroups, respectively.
      The most common treatment-related AEs in the overall population (any grade) were
      vision disorder (58%), nausea (51%), diarrhoea (47%) and vomiting (47%). PRO
      scores demonstrated clinically meaningful improvement in lung cancer symptoms and
      global quality of life. Conclusion: The efficacy, safety and PRO profiles of
      crizotinib in this cohort of 1066 patients with ALK-positive NSCLC are consistent
      with previous reports. Trial registration number: Phase 2 trial (NCT00932451);
      Results.

PMID- 29209526
TI  - The integrating nutritional therapy in oncology (INTO) project: rationale,
      structure and preliminary results.

PMID- 29209524
TI  - Heterogeneity of colon cancer: from bench to bedside.
AB  - The large bowel shows biomolecular, anatomical and bacterial changes that proceed
      from the proximal to the distal tract. These changes account for the different
      behaviour of colon cancers arising from the diverse sides of the colon-rectum as
      well as for the sensitivity to the therapy, including immunotherapy. The gut
      microbiota plays an important role in the modulation of the immune response and
      differs between the right colon cancer and the left colorectal cancer. The
      qualitative and quantitative difference of the commensal bacteria between the
      right side and the left side induces epigenetic changes in the intestinal
      epithelial cells as well as in the resident immune population. The second player
      in the pathological homeostasis of colorectal cancer is the differences of the
      genetic features of cancer cells and the different effects that microsatellite
      instability, chromosomal instability and the CpG island methylator phenotype
      induce on the immunological organisation of the tumour microenvironment. The
      third player is the immunological composition of the tumour microenvironment,
      which changes under the influence of both genetic structures and gut microbiota.
      All these three players influence each other. This review describes these three
      aspects, highlights their interactions and discusses data from reported clinical
      trials.

PMID- 29209527
TI  - Pembrolizumab as second-line therapy in non-small cell lung cancer in northern
      Norway: budget impact and expected gain-a model-based analysis.
AB  - Background: Pembrolizumab is a new drug approved in several countries for second
      line therapy in non-small cell lung cancer (NSCLC) being programmed cell death
      ligand (PD-L1) positive. This drug has a high cost, and the cost-effectiveness
      ratio has been debated. Patients and methods: The budget impact to the Northern
      Norwegian Regional Health Authority trust of implementing pembrolizumab in second
      line therapy in patients with PD-L1-positive NSCLC was calculated. A model was
      developed employing data from the Cancer Registry of Norway, the KEYNOTE-010
      study, the price list from The Hospital Pharmacy of North Norway, the cost of
      analysing PD-L1 expression and the cost of travelling. Today's cost of second
      line therapy was compared with the new standard employing pembrolizumab. The sale
      price of pembrolizumab in Norway was not published due to price confidentiality.
      Norwegian krone (NKr) was converted into Euros (?) at a rate of 1?=Nkr 8.8138.
      (Bank of Norway, 21 February 2017). Results: 105 new patients were identified
      available for pembrolizumab per year. The annual cost of pembrolizumab was ?5.2
      million, hospital pharmacy administration costs ?0.1 million, PD-L1 testing ?0.3
      million, oncologist/pulmonologist/nurses ?0.2 million, radiology ?0.06 million
      and transportation ?0.4 million. Savings due to avoided present second-line
      therapy was calculated ?0.4 million. Consequently, the cost of implementing
      pembrolizumab was ?5.5 million and the annual budget impact was ?5.0 million. A
      mean gain of at least 9 months per patient treated was necessary to make
      pembrolizumab cost-effective. Conclusions: The net budget impact of pembrolizumab
      was ?5.0 million. The expenditure could not be indicated cost-effective. Price
      confidentiality is a growing problem in health economics and it has become a
      'menu without prices' setting.

PMID- 29209528
TI  - Cancer and the arts: metastasis-as perceived through the ages.

PMID- 29209529
TI  - Patient-reported pain severity, pain interference and health status in HR+/HER2-
      advanced/metastatic breast cancer.
AB  - Introduction: Patient-reported pain severity and related impact in
      advanced/metastatic breast cancer (ABC/MBC) are not well documented. The
      objective of this study was to assess pain and general health status in hormone
      receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)
      ABC/MBC. Methods: Data were collected in the USA and Europe in a real-world,
      cross-sectional study. Patients were recruited at oncology practices and
      completed validated questionnaires; pain severity and interference were assessed
      using the Brief Pain Inventory (BPI) and general health status using the EuroQoL
      5D (EQ-5D-3L). Descriptive statistics were generated for the overall cohort, and
      stratified by type of therapy and sites of metastases. Differences between
      patient groups were assessed via the Mann-Whitney Wilcoxon test. The relationship
      between pain scores and general health status was assessed using Kruskal-Wallis
      tests. Results: Overall, 173 oncologists and 739 patients participated. The
      majority of patients rated their worst pain, average pain and pain interference
      as mild (59%, 77% and 70%, respectively). Most patients (>90%) reported no
      problems or moderate problems for all items of the EQ-5D-3L. Current treatment
      had no significant associations with pain severity or interference. Patients on
      chemotherapy reported significantly higher proportions of moderate/extreme levels
      of anxiety/depression (66.7%) and significantly lower general health status
      (60.7) compared with those on endocrine therapy (53.1% and 64.4, respectively).
      Pain severity and interference, all EQ-5D-3L items except self-care and the EQ-5D
      3L health utility index were also significantly associated with sites of
      metastases, with greater impact in patients with visceral and bone metastases
      than those with bone only or visceral only metastases. Significant associations
      were observed between pain and health status, with increased pain severity and
      pain interference associated with worse health utility and general health status.
      Conclusion: There is a clear unmet need for treatments that can reduce pain and
      preserve health status in patients with HR+/HER2- ABC/MBC.

PMID- 29209531
TI  - Rituximab biosimilars open new horizons in immunotherapy.

PMID- 29209530
TI  - Teleconsultation ultrasonography: a new weapon to combat cholangiocarcinoma.
AB  - Although cholangiocarcinoma (CCA) is usually a rare cancer, in northeast Thailand
      it kills 20 000 or more people every year. The prognosis is very poor owing to
      late stage diagnosis, with palliative treatment often representing the only
      option. In this area of predominantly rural Thailand, CCA is associated with
      infection with the liver fluke, Opisthorchis viverrini, which is classified as a
      group 1 carcinogen. Up to 6 million Thais are infected with this fluke. The
      Cholangiocarcinoma Screening and Care Program (CASCAP) was initiated in 2014 with
      the aim of detecting early stage CCA, allowing curative surgery, by using
      ultrasound (US) screening of prospectively 500 000 at risk individuals. In order
      to assess the massive number of radiological images, a teleconsultation system
      was set-up. This allows US images to be sent to a dedicated server where they can
      be viewed by an expert radiologist who then provides a provisional diagnosis,
      recommending more advanced diagnostic techniques (CT and MRI) for suspected
      cases. To date, 250 000 people have been screened, and 2000 cases of CCA
      diagnosed. This innovative information transfer procedure will also be made
      available to Laos, Cambodia and Vietnam, where O. viverrini infection is also
      common.

PMID- 29209532
TI  - ESMO Open welcomes the association with the Japanese Society of Medical Oncology
      (JSMO).

PMID- 29209533
TI  - Vinorelbine in BRAF V600E mutated metastatic colorectal cancer: a prospective
      multicentre phase II clinical study.
AB  - Background: BRAF V600E mutation defines a specific colorectal cancer (CRC)
      subgroup with poor prognosis. Promising preclinical data showed synthetically
      lethal activity of mitotic spindle poisons on BRAF-mutated and BRAF-like CRC
      models. We designed a phase II trial to test the activity of vinorelbine in
      patients with BRAF V600E mutated metastatic CRC (mCRC). Patients and methods:
      Patients progressed to or not deemed eligible for standard treatments received
      oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21
      days. Primary endpoint was objective response rate (ORR). Results: Twenty
      patients were enrolled; 75% of them were highly pretreated. No responses were
      observed (0%); only one patient had a confirmed disease stabilisation (5%).
      Median progression-free survival was 1 month (95% CI 0.8 to 1.8), median overall
      survival was 2.1 months (95% CI 1.6 to 3.7). No serious adverse events were
      observed. Conclusions: Despite encouraging preclinical data, our study did not
      show signs of clinical activity for vinorelbine in this patients' population.
      Further investigations on molecular heterogeneity and dynamic evolution of BRAF
      V600E mutated mCRC are needed.

PMID- 29209534
TI  - Cancer and the arts: how often do doctors only see what they want to see? Or: the
      case of an 'epidemic of breast cancer among famous artists'.

PMID- 29209535
TI  - Do patients with reduced or excellent performance status derive the same clinical
      benefit from novel systemic cancer therapies? A systematic review and meta
      analysis.
AB  - Background: Whether patients with excellent and reduced performance status (PS)
      derive different net clinical benefit from novel anticancer systemic therapies on
      clinical trials is unclear. Materials and methods: A systematic review was
      conducted of randomised controlled trials (RCTs) cited for drug approvals between
      2006 and August 2015 by the Food and Drug Administration, the European Medicines
      Agency and Health Canada. Included studies had overall survival (OS) and/or
      progression-free survival (PFS) primary endpoints. Meta-analyses of OS/PFS based
      on PS dichotomised into excellent and reduced subgroups were performed using
      random effects. Results: The systematic review identified 110 RCTs, with none
      reporting PS subgroup analyses for toxicity and 66 (60%) for efficacy. For these
      66 RCTs involving 44 511 patients, pooled HRs for excellent and reduced groups
      were 0.65 (95% CI 0.61 to 0.70) and 0.67 (95% CI 0.62 to 0.72), respectively,
      with no difference between the two groups (p=0.68). Sensitivity analyses based on
      drug or cancer type and type of endpoints (OS or PFS) demonstrated similar
      results. Conclusions: No decrease in relative efficacy from novel systemic
      therapy was found for patients with reduced PS when compared with patients with
      excellent PS for the range which were included in modern RCTs. Reporting of PS
      subgroup analyses of toxicities and more inclusion of patients with borderline
      low PS in RCTs should be considered for a more comprehensive understanding of the
      net clinical benefits of contemporary systemic therapies in patients across the
      spectrum of different PS.

PMID- 29209536
TI  - Activating HER2 mutations as emerging targets in multiple solid cancers.
AB  - The epidermal growth factor receptor (EGFR) family of transmembrane receptor
      tyrosine kinases activates signalling pathways regulating cellular proliferation
      and survival. HER2 is a non-ligand-binding member of this family and exerts its
      activity through heterodimerisation with other EGFR family members. HER2
      functional activation promotes oncogenesis, leading to the investigation of HER2
      directed agents in cancers with HER2 alterations. This has been best
      characterised in the context of HER2 gene amplification in breast and gastro
      oesophageal cancers, for which HER2-directed drugs form part of standard
      treatment regimens. More recently, somatic HER2 gene mutations have been detected
      in a range of human cancer types. Preclinical data suggest that functionally
      activating HER2 mutations may drive and maintain cancers in a manner analogous to
      HER2 gene amplification and that HER2 mutations may similarly confer sensitivity
      to HER2-directed drugs. Here, we critically review the emerging roles for HER2
      directed drugs in HER2 mutant cancers. We review data from experimental models,
      where our knowledge of the underlying biology of HER2 mutational activation
      remains incomplete. We discuss clinical data from Phase I and II clinical trials
      which evaluate HER2-directed agents (tyrosine kinase inhibitors and antibody
      based drugs) in several cancer types. We highlight the heterogeneity of HER2
      mutations in human cancers, differences in the clinical efficacy of HER2-directed
      drugs between cancer types and possible mechanisms of primary and acquired
      resistance, in order to guide clinical practice and future drug development.

PMID- 29209537
TI  - Health extension workers improve tuberculosis case finding and treatment outcome
      in Ethiopia: a large-scale implementation study.
AB  - Background: Tuberculosis (TB) is a major cause of death in Ethiopia. One of the
      main barriers for TB control is the lack of access to health services. Methods:
      We evaluated a diagnostic and treatment service for TB based on the health
      extension workers (HEW) of the Ethiopian Health Extension Programme in Sidama
      Zone, with 3.5 million population. We added the services to the HEW routines and
      evaluated their effect over 4.5 years. 1024 HEWs were trained to identify
      individuals with symptoms of TB, request sputum samples and prepare smears.
      Smears were transported to designated laboratories. Individuals with TB were
      offered treatment at home or the local health post. A second zone (Hadiya) with
      1.2 million population was selected as control. We compared TB case notification
      rates (CNR) and treatment outcomes in the zones 3 years before and 4.5 years
      after intervention. Results: HEWs identified 216 165 individuals with symptoms
      and 27 918 (12%) were diagnosed with TB. Smear-positive TB CNR increased from 64
      (95% CI 62.5 to 65.8) to 127 (95% CI 123.8 to 131.2) and all forms of TB
      increased from 102 (95% CI 99.1 to 105.8) to 177 (95% CI 172.6 to 181.0) per 100
      000 population in the first year of intervention. In subsequent years, the smear
      positive CNR declined by 9% per year. There was no change in CNR in the control
      area. Treatment success increased from 76% before the intervention to 95% during
      the intervention. Patients lost to follow-up decreased from 21% to 3% (p<0.001).
      Conclusion: A community-based package significantly increased case finding and
      improved treatment outcome. Implementing this strategy could help meet the
      Ethiopian Sustainable Development Goal targets.

PMID- 29209538
TI  - Disclosure of Parental HIV Status to Children: Experiences of Adults Receiving
      Antiretroviral Treatment at an Urban Clinic in Kampala, Uganda.
AB  - Limited data are available on the experiences of parental HIV disclosure to
      children in Uganda. We conducted a qualitative study comprising sixteen in-depth
      interviews and four focus group discussions with parents receiving highly active
      antiretroviral therapy. Analysis was done using Atlas.ti qualitative research
      software. Back-and-forth triangulation was done between transcripts of the in
      depth interviews and focus group discussions, and themes and subthemes were
      developed. Barriers to parents' disclosure included perceptions that children are
      too young to understand what HIV infection means and fears of secondary
      disclosure by the children. Immediate outcomes of disclosure included children
      getting scared and crying, although such instances often gave way to more
      enduring positive experiences for the parents, such as support in adherence to
      medical care, help in household chores, and a decrease in financial demands from
      the children. Country-specific interventions are needed to improve the process of
      parental HIV disclosure to children and this should encompass preparation on how
      to deal with the immediate psychological challenges associated with the parent's
      disclosure.

PMID- 29209539
TI  - Proposing Development and Utility of a Mobility Composite Measure in Patients
      with a Neurologic Disorder.
AB  - Background: Outcome measures typically assess single domains making holistic
      assessment difficult. Our purpose was to develop a mobility composite measure
      (MCM) based on four commonly used outcome measures and compare this composite
      score to the individual measures in patients with neurologic disorders. Methods:
      We retrospectively reviewed 148 medical records for inclusion of primary
      neurologic diagnosis and scoring for 5 times sit-to-stand test (5TSST), 10-meter
      walk test (10MWT), 2-minute walk test (2MWT), and activities-specific balance
      confidence (ABC) scale. Results: After establishing that a single concept was
      being assessed with interitem correlations, raw scores were converted to
      percentage of normal and combined into the MCM for analysis from admission to
      discharge. Scores on each measure significantly improved after intervention
      (5TSST, p < .001; 10MWT, p < .001; 2MWT, p < .001; ABC, p = .02). Mean MCM (n =
      93) admission scores were 67.55 +/- 31.88% and discharge scores were 74.81 +/-
      34.39% (p = .002). On average, patients improved 7.26% on the MCM exceeding the
      threshold of expected error (MDC95 = 3.59%). Conclusions: MCM detected change in
      patient outcomes statistically and clinically and appears to capture a holistic
      picture of functional status. We recommend a prospective study to further
      investigate a "composite measure" incorporating measures from several functional
      domains.

PMID- 29209540
TI  - Deglutition Syncope: Two Case Reports Attributed to Vagal Hyperactivity.
AB  - Deglutition syncope is a relatively rare cause of syncope that belongs to the
      category of neurally mediated reflex syncopal syndromes. The phenomenon is
      related to vagal reflex in context to deglutition causing atrioventricular block
      and acute reduction in cardiac output leading to dizziness or syncope. We present
      case series of two cases of deglutition syncope, of which first was managed
      medically and second with pacemaker implantation.

PMID- 29209541
TI  - A Rare Manifestation of Asymptomatic Ebstein's Anomaly with Tricuspid Valve
      Endocarditis.
AB  - Ebstein's anomaly is a rare congenital heart disease that presents with apical
      displacement of the septal and posterior leaflets of the tricuspid valve. It has
      a wide spectrum of clinical presentations and has been shown to manifest itself
      any time from birth to adulthood. Our patient is a 43-year-old male with a
      history of intravenous heroin abuse who presented to the emergency department
      with worsening shortness of breath and lower extremity edema. He denied any prior
      cardiac history. A transthoracic echo showed normal left ventricular function,
      but a large 2.2 * 2.1 cm echodensity on the septal leaflet of the tricuspid valve
      consistent with vegetation with severe tricuspid regurgitation and probable
      leaflet perforation. It also demonstrated severe right heart enlargement with
      atrialization of the right ventricle and apical displacement of the tricuspid
      valve consistent with Ebstein's anomaly. This is a rare case of an adult who
      presented with asymptomatic Ebstein's anomaly. There have been few reports of
      tricuspid valve endocarditis with Ebstein's anomaly in the literature. To our
      knowledge, this represents the fifth reported case of a new diagnosis of
      Ebstein's anomaly in the setting of endocarditis and the second case of Ebstein's
      anomaly and endocarditis in an intravenous drug abuser.

PMID- 29209542
TI  - Skin Lesions Associated with Nutritional Management of Maple Syrup Urine Disease.
AB  - Introduction: Maple syrup urine disease (MSUD) is an inborn error of branched
      chain amino acids (BCAAs) metabolism. We report an infant with MSUD who developed
      2 episodes of cutaneous lesions as a result of isoleucine deficiency and zinc
      deficiency, respectively. Case Presentation: A 12-day-old male infant was
      presented with poor milk intake and lethargy. The diagnosis of MSUD was made
      based on clinical and biochemical data. Management and Outcome: Specific dietary
      restriction of BCAAs was given. Subsequently, natural protein was stopped as the
      patient developed hospital-acquired infections which resulted in an elevation of
      BCAAs. Acrodermatitis dysmetabolica developed and was confirmed to be from
      isoleucine deficiency. At the age of 6 months, the patient developed severe
      lethargy and was on natural protein exclusion for an extended period. Despite
      enteral supplementation of zinc sulfate, cutaneous manifestations due to zinc
      deficiency occurred. Discussion: Skin lesions in MSUD patients could arise from
      multiple causes. Nutritional deficiency including isoleucine and zinc
      deficiencies can occur and could complicate the treatment course as a result of
      malabsorption, even while on enteral supplementation. Parenteral nutrition should
      be considered and initiated accordingly. Clinical status, as well as BCAA levels,
      should be closely monitored in MSUD patients.

PMID- 29209543
TI  - A Rare Case of Endometrial Cancer Metastatic to the Sigmoid Colon and Small
      Bowel.
AB  - Metastatic endometrial cancer to the small bowel or colon has been described but
      is quite rare. We present a case of metastatic endometrial cancer with
      synchronous metastases to the colon and jejunum identified three years after
      surgical treatment of early stage endometrial cancer.

PMID- 29209544
TI  - A Case of Proliferative Glomerulonephritis with Monoclonal IgG Deposits That
      Showed Predominantly Membranous Features.
AB  - In 2004, the novel category of monoclonal IgG deposition disease has been
      proposed and termed "proliferative glomerulonephritis with monoclonal IgG
      deposits" (PGNMID). This disease is characterized by membranoproliferative
      glomerulonephritis and staining for a single light-chain isotype and gamma heavy
      chain subclass. A 76-year-old male who had monoclonal gammopathy was referred to
      our hospital because of proteinuria. The renal biopsy showed diffuse thickening
      of the glomerular capillary walls with focal mesangial proliferation. On
      immunofluorescence study, only IgG1 among the four subclasses and lambda light
      chains were detected mainly in the glomerular capillary walls. From these
      results, we diagnosed our case as PGNMID showing predominantly membranous
      features. Almost all pathological findings on light microscopy of PGNMID are
      membranoproliferative GN or endocapillary proliferative GN, while membranous GN
      cases are rare. Here, we present the case of PGNMID that showed predominantly
      membranous features on light microscopy.

PMID- 29209545
TI  - Difficult to Treat Focal, Stiff Person Syndrome of the Left Upper Extremity.
AB  - Background: Stiff person syndrome (SPS) is a rare neurologic disorder
      characterized by muscle rigidity. It is a disorder of reduced GABA activity
      leading to increased muscle tone and often painful spasms. It generally presents
      in the axial musculature but rarely can involve only one limb, typically a lower
      extremity. In rare cases it can be paraneoplastic which generally resolves on
      treatment of the underlying neoplasm. Case Report: A 46-year-old male with a
      history of Hodgkin's Lymphoma in remission presented with left upper extremity
      pain secondary to a diagnosis of Stiff Person Syndrome limited to his left upper
      extremity. He had previously benefitted from plasmapheresis and was on diazepam
      and baclofen at home with relatively good control of his symptoms. SPS had
      previously been diagnosed with EMG and anti-GAD-65 antibody titers and was
      confirmed by an elevated anti-GAD-65 antibody titer. He was treated with
      plasmapheresis and maximum doses of medical treatment including botulinum toxin
      with only transient mild improvement in his symptoms. Conclusion: This case
      represents a case of a rare disease that was refractory to all known therapies.
      It outlines the need for further understanding of this disorder in order to
      provide better symptomatic treatment or potentially more definitive care.

PMID- 29209546
TI  - Unilateral Cervical Lymphadenopathy due to Cladosporium oxysporum: A Case Report
      and Review of the Literature.
AB  - Phaeohyphomycosis is a fungal infection caused by Dermatiacae group of fungi, by
      Cladosporium spp. The term phaeohyphomycosis was introduced by Ajello et al. in
      1974 to designate infections by brown pigmented filamentous fungi. Cladosporium
      oxysporum is a very rare etiological agent in humans. Phaeohyphomycosis of the
      cervical lymph node in an immunocompetent individual is a very rare clinical
      entity. To the best of our knowledge we report the first case of
      phaeohyphomycosis caused by Cladosporium oxysporum in the absence of other
      systemic manifestations in a 16-year-old male.

PMID- 29209547
TI  - An Acquired Form of Dandy-Walker Malformation with Enveloping Hemosiderin
      Deposits.
AB  - Dandy-Walker malformation (DWM) is a posterior fossa anomaly characterized by
      hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of
      the fourth ventricle. The cyst of DWM rarely extends posteriorly to almost
      completely fill the entire posterior fossa, which mimics primary cerebellar
      agenesis, a cerebellar porencephalic cyst, and an arachnoid cyst due to the lack
      of clarity of the thin cystic wall. A 10-month-old female born at 23 weeks'
      gestation with cerebellar hemorrhage in the neonatal period was admitted to our
      hospital with dysphagia and side-to-side head bobbing. The detection of
      hemosiderin deposits enveloping the cyst wall by T2 star-weighted angiography
      (SWAN) was useful for the differential diagnosis of an acquired form of DWM from
      primary cerebellar agenesis. Cyst fenestration successfully improved dysphagia
      and head bobbing. A pathological specimen of the perforated cyst consisted of
      collagen fibers with hemosiderin deposits but lacked congenital cyst components.
      In infants with posterior fossa cysts, SWAN will be useful for a differential
      diagnosis between DWM and primary cerebellar agenesis.

PMID- 29209548
TI  - Use of Interpersonal Counseling for Modern Type Depression.
AB  - A novel form of depression, called "modern type depression" (MTD), has been
      increasing in prevalence in Japan. Patients with MTD present with an overt appeal
      of depressive mood and a desire to be excused from their work duties; as such,
      this can cause considerable trouble in the workplace. Psychosocial interventions
      should be primarily considered for the treatment of MTD. Interpersonal counseling
      (IPC), which has proven effective for treating subthreshold depression, may be
      effective for MTD. However, IPC is rarely done in Japan. Herein, we report on a
      successful case of IPC for a woman in her thirties who was about to quit her job
      due to MTD (diagnosed by the criteria for research use). After IPC, the patient
      enjoyed good communication with her boss and continued her job without succumbing
      to her depression. This case suggests that IPC may be effective for MTD in
      workers and further highlights the benefits of teaching interpersonal
      communication methods in the workplace.

PMID- 29209549
TI  - Macrophage Activation Syndrome: A Report of Two Cases and a Literature Review.
AB  - Macrophage activation syndrome (MAS) is a severe, potentially fatal condition
      that may complicate autoimmune diseases, and it belongs to hemophagocytic
      lymphohistiocytosis (HLH) disorders. MAS occurs in adults and children. However,
      it is rare in juvenile systemic lupus erythematosus (jSLE), and it is extremely
      rare to be the initial presentation of jSLE. Here, we report two patients with
      juvenile SLE who initially presented with MAS. One of the two patients is 4 years
      old. This is the youngest reported patient to our knowledge.

PMID- 29209550
TI  - Rare Case of Large Bowel Injury due to Direct Blunt Trauma to a Preexisting
      Femoral Hernia.
AB  - We report a case of an 85-year-old man with a known asymptomatic left femoral
      hernia who was admitted to the emergency ward a few hours after falling from a
      bicycle and suffering from blunt trauma of the handlebar to the left inguinal
      region. The clinical findings and a computed tomography (CT) scan detecting free
      air in the femoral hernia sac suggested bowel perforation. Emergency laparotomy 6
      hours after the incident confirmed a tear of the sigmoid colon accompanied by
      free blood and faeces in the left inguinal region of the abdomen. A segmental
      sigmoid resection and a primary end-to-end colorectal anastomosis were performed.
      The postoperative course was complicated by delayed oral feeding, a local
      infection, and a partial left testicle necrosis that led to secondary resection.
      The patient was discharged after 32 days of in-hospital care. Three months post
      trauma, we recorded a restitutio ad integrum. The case exemplifies that blunt
      trauma to preexisting femoral hernias may cause potentially lethal bowel
      perforation and that the time interval between time of injury and surgical
      treatment may be a prognostic factor. CT scans seem most suitable for ruling out
      bowel perforation. The scarce literature for blunt trauma to hernias is reviewed.

PMID- 29209551
TI  - Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon
      Adenocarcinoma.
AB  - A 65-year-old female patient presented to the emergency clinic with abdominal
      pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and
      a hepatic flexure tumor was detected. Histopathological examination of biopsy
      revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a
      spiculated contour mass was found incidentally on the left breast. Mammography
      and ultrasonography were performed for the cause of these findings, and
      suspicious lesions of malignancy were seen in the left breast. Invasive ductal
      carcinoma was detected in core needle biopsy samples from lesions. In the
      multidisciplinary council consisting of oncologist, pathologist, radiologist, and
      general surgery specialist, it was decided to perform breast operation first and
      then colon operation, followed by adjuvant chemotherapy. In the first operation,
      left total mastectomy and sentinel lymph node biopsy were performed. One week
      after her initial operation, the patient underwent right hemicolectomy. After
      operations, the patient did not develop postoperative complications and was sent
      to medical oncology department for adjuvant chemotherapy.

PMID- 29209552
TI  - Corrigendum to "Challenges in Interpretation of Thyroid Function Tests in
      Pregnant Women with Autoimmune Thyroid Disease".
AB  - [This corrects the article DOI: 10.4061/2011/598712.].

PMID- 29209553
TI  - Antidyskinetic Treatment with MTEP Affects Multiple Molecular Pathways in the
      Parkinsonian Striatum.
AB  - Parkinson's disease is characterized by dopaminergic neuron loss and dopamine
      (DA) depletion in the striatum. Standard treatment is still focused on the
      restoration of dopamine with exogenous L-Dopa, which however causes L-Dopa
      induced dyskinesia (LID). Several studies have shown that antagonism of the
      metabotropic glutamate receptor 5 alleviates LID, but the underlying mechanisms
      have remained unclear. We set out to determine where this alleviation may depend
      on restoring the equilibrium between the two main striatofugal pathways. For this
      purpose, we examined molecular markers of direct and indirect pathway involvement
      (prodynorphin and proenkephalin, resp.) in a rat model of LID treated with the
      mGluR5 antagonist MTEP. Our results show that MTEP cotreatment significantly
      attenuates the upregulation of prodynorphin mRNA induced by L-Dopa while also
      decreasing the expression levels of proenkephalin mRNA. We also examined markers
      of the mGluR5-related PKC/MEK/ERK1/2 signaling pathway, finding that both the
      expression of PKC epsilon and the phosphorylation of MEK and ERK1/2 had decreased
      significantly in the MTEP-treated group. Taken together, our results show that
      pharmacological antagonism of mGluR5 normalizes several abnormal molecular
      responses in the striatum in this experimental model of LID.

PMID- 29209554
TI  - Genetic Analysis of LRRK2 R1628P in Parkinson's Disease in Asian Populations.
AB  - Although the etiology of Parkinson's disease (PD) remains unclear, there is
      increasing evidence of genetic factors contributing to the onset of PD. Various
      mutations and risk variants of the gene LRRK2 have been reported, but the
      association between LRRK2 R1628P and PD is still inconsistent. Thus, we conducted
      a meta-analysis to determine the potential relationship between R1628P and PD.
      Our study sample was an aggregate of 17 publications, which in total consisted of
      9,275 PD patients and 8,114 controls. All of these articles are of high quality
      according to NOS, and there was no obvious reporting bias or heterogeneity. In a
      general Asian population, the pooled OR of the risk genotype contrasts was 1.83
      (95% CI: 1.57, 2.13). When stratified by ethnicity, the pooled ORs were 1.84 (95%
      CI: 1.56, 2.18) in a Chinese population and 1.79 (95% CI: 1.27, 2.52) in a non
      Chinese population. Our study suggests that LRRK2 R1628P appears to be a risk
      factor for PD in Asian populations, both Chinese and non-Chinese.

PMID- 29209555
TI  - Validating Analytical Protocols to Determine Selected Pesticides and PCBs Using
      Routine Samples.
AB  - This study aims at providing recommendations concerning the validation of
      analytical protocols by using routine samples. It is intended to provide a case
      study on how to validate the analytical methods in different environmental
      matrices. In order to analyze the selected compounds (pesticides and
      polychlorinated biphenyls) in two different environmental matrices, the current
      work has performed and validated two analytical procedures by GC-MS. A
      description is given of the validation of the two protocols by the analysis of
      more than 30 samples of water and sediments collected along nine months. The
      present work also scopes the uncertainty associated with both analytical
      protocols. In detail, uncertainty of water sample was performed through a
      conventional approach. However, for the sediments matrices, the estimation of
      proportional/constant bias is also included due to its inhomogeneity. Results for
      the sediment matrix are reliable, showing a range 25-35% of analytical
      variability associated with intermediate conditions. The analytical methodology
      for the water matrix determines the selected compounds with acceptable recoveries
      and the combined uncertainty ranges between 20 and 30%. Analyzing routine samples
      is rarely applied to assess trueness of novel analytical methods and up to now
      this methodology was not focused on organochlorine compounds in environmental
      matrices.

PMID- 29209556
TI  - Chinese Herbal Medicines as Potential Agents for Alleviation of Heat Stress in
      Poultry.
AB  - Heat stress negatively affects the productivity of chickens in commercial poultry
      farms in humid tropics. In this study, the concentrations and types of the
      antioxidant compounds of eight Chinese herbal medicines, which have previously
      demonstrated promising effects on suppressing heat stress as a mixture, were
      investigated using reversed-phase High Performance Liquid Chromatography,
      spectrophotometry, Liquid Chromatography Mass Spectrometry, and Gas-Liquid
      Chromatography. Our results provided the levels of phenolic compounds, total
      amounts of sugars, and total unsaturated fatty acids in the herbal extracts.
      Apart from the detection and quantification of the active ingredients of herbs
      that have the potential to mitigate heat stress in poultry, results of this study
      also provide useful data for developing an efficient and accurate formulation of
      the herbs' mixtures in order to induce positive effects against heat stress in in
      vivo studies.

PMID- 29209557
TI  - LINE-1 in response to exposure to ionizing radiation.
AB  - It is becoming increasingly recognized that Long Interspersed Nuclear Element, 1
      (LINE-1), the most ubiquitous repetitive element in the mammalian genomes, plays
      an important role in the pathogenesis of disease and in the response to exposure
      to environmental stressors. Ionizing radiation is a known genotoxic stressor, but
      it is capable of targeting the cellular epigenome as well. Radiation-induced
      alterations in LINE-1 DNA methylation are the most frequently observed epigenetic
      effects of exposure. The extent of this aberrant DNA methylation, however,
      strongly depends on a number of factors, including the type and dose of
      radiation. Two other factors are being discussed in this commentary - the
      evolutionary age and type of the LINE-1 promoter, as well as the type of
      irradiated cell. This knowledge will further aid in elucidating the mechanisms of
      response to ionizing radiation exposure, as well in understanding the
      pathogenesis of the negative health effects associated with exposure.

PMID- 29209558
TI  - Development and clinical application of anti-HER2 monoclonal and bispecific
      antibodies for cancer treatment.
AB  - HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab,
      pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T
      cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a
      classic drug for the treatment of HER2 positive metastatic breast cancer. The
      combined application of pertuzumab, trastuzumab and paclitaxel has been suggested
      as a standard therapy for HER2 positive advanced breast cancer. The resistance to
      anti-HER2 antibody has resulted in disease progression. HER2-directed bispecific
      antibody may be a promising therapeutic approach for these patients. Ertumaxomab
      enhanced the interaction of immune effector cells and tumor cells. MM-111
      simultaneously binds to HER2 and HER3 and blocks downstream signaling. Besides,
      HER2Bi-aATC is also an alternative therapeutic approach for HER2 positive
      cancers. In this review, we summarized the recent advancement of HER2-targeted
      monoclonal antibodies (trastuzumab, pertuzumab and T-DM1) and bispecific
      antibodies (MM-111, ertumaxomab and HER2Bi-aATC), especially focus on clinical
      trial results.

PMID- 29209559
TI  - NKp46 expression on NK cells as a prognostic and predictive biomarker for
      response to allo-SCT in patients with AML.
AB  - NKp46 is a major determinant of natural killer (NK) cell function and it is
      implicated in tumor immune surveillance in acute myeloid leukemia (AML). The
      purpose of this study was to investigate the prognostic significance of NKp46
      expression in an independent cohort of patients with AML, and to investigate the
      impact of NKp46 on clinical outcome after allogeneic stem cell transplantation
      (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow
      cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46
      expression. Patients with NKp46high phenotype at diagnosis had better progression
      free survival (PFS) and overall survival (OS) than patients with NKp46low
      phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively).
      In multivariate analysis, high NKp46 was an independent factor for improved OS
      (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis
      revealed that allo-SCT had a favorable impact on PFS in patients with NKp46high
      phenotype (p = 0.025). By contrast, allo-SCT did not impact PFS in patients with
      low NKp46 expression (p = 0.303). In conclusion, we validate the prognostic value
      of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46
      expression is limited to patients treated with allo-SCT, thus suggesting that
      NKp46 status may be predictive for allo-SCT responsiveness.

PMID- 29209560
TI  - PD-L1 and epithelial-mesenchymal transition in circulating tumor cells from non
      small cell lung cancer patients: A molecular shield to evade immune system?
AB  - The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a
      critical inhibitory pathway regulating T-cell response in non-small-cell lung
      cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the
      landscape of NSCLC therapy. Nevertheless, the high degree of non-responders
      demonstrates that we are still far from completely understanding the events
      underlying tumor immune resistance. Although the expression of PD-L1 in tumor
      tissue has been correlated with clinical response to anti PD-1 inhibitors, the
      ability of this marker to discriminate the subgroup of patients who derive
      benefit from immunotherapy is suboptimal. Circulating tumor cells (CTCs), as an
      accessible source of tumor for biologic characterization that can be serially
      obtained with minimally invasive procedure, hold significant promise to
      facilitate treatment-specific biomarkers discovery. We recently demonstrated that
      the presence of PD-L1 on CTCs apparently predicts resistance to the anti-PD-1
      Nivolumab in metastatic NSCLC patients and that PD-L1 positive CTCs usually have
      an elongated morphology that can be ascribed to epithelial-mesenchymal transition
      (EMT). We here demonstrate for the first time that PD-L1 positive CTCs isolated
      from NSCLC patients are characterized by partial EMT phenotype, and hypothesize
      that the co-expression of PD-L1 and EMT markers might represent for these cells a
      possible molecular background for immune escape.

PMID- 29209561
TI  - Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in
      stage III colorectal cancer.
AB  - Tumor-associated macrophages (TAMs) play a role in tumor development and
      progression. We hypothesized that abundance of TAMs might modify efficacy of 5
      fluorouracil chemotherapy in colorectal cancer. We measured the density of CD68+
      TAMs at the invasive front of primary tumor of colorectal carcinoma (PT-TAMs; n =
      208), at available matched metastatic lymph node (LN-TAMs; n = 149), and in an
      independent set of primary colorectal cancers (PT-TAMs, n = 111). The hazard
      ratios for disease-free survival were computed by Cox proportional-hazards model.
      In exploratory analysis, the interaction between TAMs and 5-fluorouracil adjuvant
      therapy was significant (PT-TAMs, p = 0.02; LN-TAMs, p = 0.005). High TAMs were
      independently associated with better disease-free survival only in 5-fluorouracil
      treated patients (PT-TAMs, HR 0.23; 95%CI, 0.08-0.65; p = 0.005; LN-TAMs, HR
      0.13; 95%CI, 0.04-0.43; p = 0.001). The independent predictive value of PT-TAMs
      was replicated in the external set (HR, 0.14; 95%CI 0.02-1.00; p = 0.05). In an
      in vitro experiment, 5-fluorouracil and macrophages showed a synergistic effect
      and increased colorectal cancer cell death. High densities of TAMs, particularly
      in metastatic lymph-nodes, identify stage III colorectal cancer patients
      benefitting from 5-fluorouracil adjuvant therapy.

PMID- 29209562
TI  - Collagen I enhances the efficiency and anti-tumor activity of dendritic-tumor
      fusion cells.
AB  - Low fusion efficiency and nominal activity of fusion cells (FCs) restrict the
      clinical application of dendritic cell (DC)/tumor fusion cells. Collagen I (Col
      I) is an interstitial collagen with a closely-knit structure used to repair
      damaged cell membranes. This study evaluated whether Col I could improve the
      fusion efficiency of polyethylene glycol (PEG)-induction and enhance the
      immunogenicity of fusion vaccine. DC/B16 melanoma and controlled DC/H22 hepatoma
      cell fusions were induced by PEG with or without Col I. Col I/PEG treatment
      increased the levels of DC surface molecules and the secretion of lactate, pro-
      and anti-inflammatory cytokines in fusion cells. Col I/PEG-treated FCs enhanced T
      cell proliferation and cytotoxic T lymphocyte activity. The Col I-prepared fusion
      vaccine obviously suppressed tumor growth and prolonged mice survival time. Thus
      Col I treatment could significantly improve the efficiency of PEG-induced
      DC/tumor fusion and enhance the anticancer activity of the fusion vaccine. This
      novel fusion strategy might promote the clinical application of DC/tumor fusion
      immunotherapy.

PMID- 29209563
TI  - Comparative immunologic characterization of autoimmune giant cell myocarditis
      with ipilimumab.
AB  - Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor
      immunotherapy. To improve the understanding of this complication, we performed
      immune profiling on post-mortem tissue from a patient with metastatic melanoma
      who had steroid-responsive hepatitis, steroid-refractory myocarditis, and
      shrinking lung metastases after ipilimumab treatment. Histological analysis of
      heart tissue demonstrated findings consistent with giant cell myocarditis (GCM).
      The immune infiltrate in the heart was largely comprised of CD4+ T cells, whereas
      the liver had very few T cells, and CD8+ T cells were predominant in the
      responding lung metastases. TCR sequencing identified high T cell clonality in
      the lung metastases. The TCR repertoire showed low clonality in the heart and
      minimal overlap with the liver (1.2%), but some overlap with lung metastases
      (9.9%). Transcriptional profiling identified several potential mediators of
      increased inflammation in the heart. These findings provide new insights into the
      pathogenesis of autoimmune myocarditis with ipilimumab.

PMID- 29209565
TI  - Tumor-targeted costimulation with antibody-fusion proteins improves bispecific
      antibody-mediated immune response in presence of immunosuppressive factors.
AB  - Therapeutic strategies aiming for the induction of an effective immune response
      at the tumor site can be severely hampered by the encounter of an
      immunosuppressive microenvironment. We investigated here the potential of
      concerted costimulation by tumor-directed antibody-fusion proteins with B7.1, 4
      1BBL and OX40L to enforce bispecific antibody-induced T cell stimulation in
      presence of recognized immunosuppressive factors including IL-10, TGF-beta,
      indoleamine 2,3-dioxygenase (IDO), PD-L1 and regulatory T cells. The expression
      and activity of these factors was demonstrated in the HT1080-FAP/PBMC co-culture
      setting, where individual and combined costimulation were still capable to
      enhance T cell stimulation, even though the general activation level was reduced.
      Additional blockade of TGF-beta or PD-1 resulted especially effective in further
      enhancing the degree of T cell activation. Here, best outcome was achieved by
      combined costimulation of targeted 4-1BBL and B7.1. Furthermore, their individual
      impact on the proliferation of naive, memory and effector CD8+ and CD4+ T cell
      subsets, suggest the coverage of a comprehensive T cell response. Thus, our
      costimulatory antibody-fusion proteins show great potential to support T cell
      activation in adverse conditions dictated by the tumor microenvironment.

PMID- 29209564
TI  - Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and
      controls colon tumor progression.
AB  - Inflammation and infection are key promoters of colon cancer but the molecular
      interplay between these events is largely unknown. Mice deficient in leukotriene
      B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis,
      asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred
      onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of
      intestinal tumor development and mortality. A paradoxical increase in
      inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with
      defective host response to infection. Germ-free BLT1-/-ApcMin/+ mice are free
      from colon tumors that reappeared upon fecal transplantation. Analysis of
      microbiota showed defective host response in BLT1-/- ApcMin/+ mice reshapes the
      gut microbiota to promote colon tumor development. The BLT1-/-MyD88-/- double
      deficient mice are susceptible to lethal neonatal infections. Broad-spectrum
      antibiotic treatment eliminated neonatal lethality in BLT1-/-MyD88-/- mice and
      the BLT1-/-MyD88-/-ApcMin+ mice are protected from colon tumor development. These
      results identify a novel interplay between the Toll-like receptor mediated
      microbial sensing mechanisms and BLT1-mediated host response in the control of
      colon tumor development.

PMID- 29209566
TI  - Tumor-derived exosomes educate dendritic cells to promote tumor metastasis via
      HSP72/HSP105-TLR2/TLR4 pathway.
AB  - How the tumor microenvironment educates dendritic cells (DCs) to promote
      tumorigenesis remains largely unknown, and the role of tumor-derived exosomes
      (TEXs) in tumorigenesis is controversial. Here, we report that in addition to the
      activation of DCs, TEXs induce DCs to produce increased interleukin-6 (IL-6),
      which dramatically promotes tumor invasion by increasing signal transducer and
      activator of transcription 3 (STAT3)-dependent matrix metalloproteinases 9
      transcription activity in tumor cells. HSP72 and HSP105 on the TEX surface induce
      IL-6 secretion of DCs in a TLR2- and TLR4-dependent manner. In addition, HSP72
      and HSP105 are predominantly present on exosomes from sera of tumor patients but
      not healthy people, indicating their value in tumor prediction. Furthermore, TEXs
      are powerful activators of DCs, and the depletion of IL-6 converts TEXs from
      tumor promoters to tumor inhibitors in vivo. Therefore, our results reveal a
      novel mechanism for the TEX-mediated education of DCs and shed light on the
      conundrum that TEXs present by playing dual roles in tumorigenesis.

PMID- 29209567
TI  - Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure
      inhibit prostate tumor growth in TRAMP mice.
AB  - Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)
      inactivated tumor cells have recently been shown to be a promising tool for
      prostate cancer chemoimmunotherapy. In this study, DC-based vaccines, both pulsed
      and unpulsed, were as effective as docetaxel (DTX) in reducing prostate tumors in
      the orthotopic transgenic adenocarcinoma of the mouse prostate (TRAMP) model.
      However, we did not observe any additive or synergic effects of
      chemoimmunotherapy on the tumor growth, while only the combination of DTX and
      pulsed dendritic cells resulted in significantly lower proliferation detected by
      Ki67 staining in histological samples. The DC-based vaccine pulsed with HHP
      treated tumor cells was also combined with another type of cytostatic,
      cyclophosphamide, with similar results. In another clinically relevant setting,
      minimal residual tumor disease after surgery, administration of DC-based vaccines
      after the surgery of poorly immunogenic transplanted TRAMP-C2, as well as in
      immunogenic TC-1 tumors, reduced the growth of tumor recurrences. To identify the
      effector cell populations after DC vaccine application, mice were twice immunized
      with both pulsed and unpulsed DC vaccine, and the cytotoxicity of the spleen
      cells populations was tested. The effector cell subpopulations were defined as
      CD4+ and NK1.1+, which suggests rather unspecific therapeutic effects of the DC
      based vaccines in our settings. Taken together, our data demonstrate that DC
      based vaccines represent a rational tool for the treatment of human prostate
      cancer.

PMID- 29209568
TI  - Phenotype and tissue distribution of CD28H+ immune cell subsets.
AB  - CD28H is a newly discovered co-receptor of the human B7 family. CD28H interacts
      with its ligand B7-H5 and regulates T cell response. Here we showed that CD28H
      was not expressed on granulocytes, monocytes, myeloid dendritic cells (MDCs), and
      B cells, but constitutively expressed with moderate levels on memory T cells and
      with high levels on naive T cells, innate lymphoid cells (ILCs), natural killer
      (NK) cells, and plasmacytoid dendritic cells (PDCs) in human peripheral blood.
      Similar CD28H+ cell profile existed in secondary lymphoid organs and pathological
      tissues including multiple types of cancers. Further analysis demonstrated that
      CD28H+ naive and CD28H+ memory T cells were characterized with increased naive
      feature and less effector functional phenotype, respectively. High levels of
      constitutive CD28H expression on naive T cells and innate immune cells suggest a
      potential role of CD28H in innate and adaptive immunity.

PMID- 29209569
TI  - Resistance to HER2-targeted anti-cancer drugs is associated with immune evasion
      in cancer cells and their derived extracellular vesicles.
AB  - Neuromedin U (NmU) -a neuropeptide belonging to the neuromedin family- plays a
      substantial role in HER2-positive breast cancer, correlating with increased
      aggressiveness, resistance to HER2-targeted therapies and overall significantly
      poorer outcome for patients. However, the mechanism through which it exerts these
      effects remains unclear. To elucidate this, initially we used HER2-positive
      breast cancer cells stably over-expressing NmU. These cells and their released
      extracellular vesicles (EVs) had increased amounts of the immunosuppressive
      cytokine TGFbeta1 and the lymphocyte activation inhibitor PD-L1. Furthermore,
      these cells also showed enhanced resistance to antibody-dependent cell
      cytotoxicity (ADCC) mediated by trastuzumab, indicating a role of NmU in
      enhancing immune evasion. All these features were also found in HER2-targeted
      drug-resistant cells which we previously found to express higher levels of NmU
      than their drug-sensitive counterparts. Interestingly, EVs from drug-resistant
      cells were able to increase levels of TGFbeta1 in drug-sensitive cells. In our
      neo-adjuvant clinical trial, TGFbeta1 levels were significantly higher in EVs
      isolated from the serum of patients with HER2-overexpressing breast cancers who
      went on to not respond to HER2-targeted drug treatment, compared with those who
      experienced complete or partial response. Taken together, our results report a
      new mechanism-of-action for NmU in HER2-overexpressing breast cancer that
      enhances resistance to the anti-tumor immune response. Furthermore, EV levels of
      TGFbeta1 correlating with patients' response versus resistance to HER2-targeted
      drugs suggests a potential use of EV-TGFbeta1 as a minimally-invasive companion
      diagnostic for such treatment in breast cancer.

PMID- 29209570
TI  - CAR T-cell immunotherapy of MET-expressing malignant mesothelioma.
AB  - Mesothelioma is an incurable cancer for which effective therapies are required.
      Aberrant MET expression is prevalent in mesothelioma, although targeting using
      small molecule-based therapeutics has proven disappointing. Chimeric antigen
      receptors (CARs) couple the HLA-independent binding of a cell surface target to
      the delivery of a tailored T-cell activating signal. Here, we evaluated the anti
      tumor activity of MET re-targeted CAR T-cells against mesothelioma. Using
      immunohistochemistry, MET was detected in 67% of malignant pleural mesotheliomas,
      most frequently of epithelioid or biphasic subtype. The presence of MET did not
      influence patient survival. Candidate MET-specific CARs were engineered in which
      a CD28+CD3zeta endodomain was fused to one of 3 peptides derived from the N and
      K1 domains of hepatocyte growth factor (HGF), which represents the minimum MET
      binding element present in this growth factor. Using an NIH3T3-based artificial
      antigen-presenting cell system, we found that all 3 candidate CARs demonstrated
      high specificity for MET. By contrast, these CARs did not mediate T-cell
      activation upon engagement of other HGF binding partners, namely CD44v6 or
      heparan sulfate proteoglycans, including Syndecan-1. NK1-targeted CARs
      demonstrated broadly similar in vitro potency, indicated by destruction of MET
      expressing mesothelioma cell lines, accompanied by cytokine release. In vivo anti
      tumor activity was demonstrated following intraperitoneal delivery to mice with
      an established mesothelioma xenograft. Progressive tumor regression occurred
      without weight loss or other clinical indicators of toxicity. These data confirm
      the frequent expression of MET in malignant pleural mesothelioma and demonstrate
      that this can be targeted effectively and safely using a CAR T-cell
      immunotherapeutic strategy.

PMID- 29209571
TI  - Complete regression of cutaneous metastases with systemic immune response in a
      patient with triple negative breast cancer receiving p53MVA vaccine with
      pembrolizumab.
AB  - A heavily pretreated patient with triple negative breast cancer distinguished by
      cutaneous metastases received p53MVA vaccine in combination with pembrolizumab.
      Her cutaneous metastases regressed and after 2 cycles of therapy, a skin biopsy
      showed a complete pathological response. Systemic response was confirmed with
      restaging CT and bone scans. Activation of p53-specific T cell responses and
      elevation of multiple immune response genes in peripheral blood correlated with
      the rapid clinical response which lasted for 6 months after the initiation of
      combined therapy.

PMID- 29209574
TI  - CARs on a highway with roadblocks.

PMID- 29209572
TI  - Trial Watch: Immunostimulatory monoclonal antibodies for oncological indications.
AB  - The goal of cancer immunotherapy is to establish new or boost pre-existing
      anticancer immune responses that eradicate malignant cells while generating
      immunological memory to prevent disease relapse. Over the past few years,
      immunomodulatory monoclonal antibodies (mAbs) that block co-inhibitory receptors
      on immune effectors cells - such as cytotoxic T lymphocyte-associated protein 4
      (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) - or their ligands -
      such as CD274 (best known as PD-L1) - have proven very successful in this sense.
      As a consequence, many of such immune checkpoint blockers (ICBs) have already
      entered the clinical practice for various oncological indications. Considerable
      attention is currently being attracted by a second group of immunomodulatory
      mAbs, which are conceived to activate co-stimulatory receptors on immune effector
      cells. Here, we discuss the mechanisms of action of these immunostimulatory mAbs
      and summarize recent progress in their preclinical and clinical development.

PMID- 29209576
TI  - PlantCV v2: Image analysis software for high-throughput plant phenotyping.
AB  - Systems for collecting image data in conjunction with computer vision techniques
      are a powerful tool for increasing the temporal resolution at which plant
      phenotypes can be measured non-destructively. Computational tools that are
      flexible and extendable are needed to address the diversity of plant phenotyping
      problems. We previously described the Plant Computer Vision (PlantCV) software
      package, which is an image processing toolkit for plant phenotyping analysis. The
      goal of the PlantCV project is to develop a set of modular, reusable, and
      repurposable tools for plant image analysis that are open-source and community
      developed. Here we present the details and rationale for major developments in
      the second major release of PlantCV. In addition to overall improvements in the
      organization of the PlantCV project, new functionality includes a set of new
      image processing and normalization tools, support for analyzing images that
      include multiple plants, leaf segmentation, landmark identification tools for
      morphometrics, and modules for machine learning.

PMID- 29209577
TI  - New anatomical information of the wukongopterid Kunpengopterus sinensis Wang et
      al., 2010 based on a new specimen.
AB  - The Wukongopteridae compose a non-pterodactyloid clade of pterosaurs that are the
      most abundant flying reptiles in the deposits of the Middle-Late Jurassic Yanliao
      Biota. Until now, five species of three genera and two additional unnamed
      specimens have been described. Here we report on a new material, IVPP V 23674,
      that can be referred to the wukongopterid Kunpengopterus sinensis due to several
      features such as a comparably short nasoantorbital fenestra, the dorsally rising
      posterodorsal margin of the ischium, and the very short first pedal phalanx of
      digit V relative to metatarsal IV. IVPP V 23674 provides the first view of a
      wukongopterid palate, which differs from all other pterosaurs by having a very
      large postpalatine fenestra and laterally compressed choanae, indicating that the
      evolution of the pterosaur palate was more complex than previously thought.
      Sesamoid bones at the dorsal side of manual unguals are present and are reported
      for the first time in a wukongopterid suggesting an arboreal life-style for these
      pterosaurs.

PMID- 29209578
TI  - Effects of shinbuto and ninjinto on prostaglandin E2 production in
      lipopolysaccharide-treated human gingival fibroblasts.
AB  - Previously, we revealed that several kampo medicines used for patients with
      excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto
      (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E2 levels using LPS
      treated human gingival fibroblasts (HGFs). Recently, we examined other kampo
      medicines used for patients with the deficiency pattern [bakumondoto (TJ-29),
      shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs
      comprising shinbuto and ninjinto using the same experimental model. Shinbuto and
      ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs,
      whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2
      production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or
      the expression of molecules involved in the arachidonic acid cascade. Therefore,
      we next examined which herbs compromising shinbuto and ninjinto reduce LPS
      induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and
      kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently
      decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased
      the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or
      COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2
      activity. We demonstrated that kampo medicines suppress inflammatory responses in
      patients with the deficiency pattern, and in those with excess or medium
      patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered
      to be effective for the treatment of inflammatory diseases.

PMID- 29209579
TI  - Unanticipated discovery of two rare gastropod molluscs from recently located
      hydrothermally influenced areas in the Okinawa Trough.
AB  - Background: The deep-sea hydrothermal vent is one of the most 'extreme'
      environments in the marine realm. Few species are capable of inhabiting such
      ecosystems, despite extremely high productivity there supported by microbial
      chemosynthesis, leading to high biomass and low species richness. Although
      gastropod molluscs are one of the main constituents of megafaunal communities at
      vent ecosystems, most species belong to several typical families (e.g.,
      Provannidae, Peltospiridae, Lepetodrilidae) specialised and adapted to life at
      vents. Methods: During recent surveys of Okinawa Trough hydrothermal vent
      systems, two snails atypical of vent ecosystems were unexpectedly found in newly
      discovered hydrothermally influenced areas. Shell and radular characteristics
      were used to identify the gastropods morphologically. Results: One species was a
      vetigastropod, the calliostomatid Tristichotrochus ikukoae (Sakurai, 1994); and
      the other was a caenogastropod, the muricid Abyssotrophon soyoae (Okutani, 1959).
      Both gastropods were previously only known from regular non-chemosynthetic deep
      sea and very rare-only two definitive published records exist for T. ikukoae and
      three for A. soyoae. The radula formula of Tristichotrochus ikukoae is accurately
      reported for the first time and based on that it is returned to genus Otukaia.
      For both species, barcode sequences of the cytochrome c oxidase I (COI) gene were
      obtained and deposited for future references. Discussion: These new records
      represent the second record of calliostomatids from vents (third from
      chemosynthetic ecosystems) and the third record of muricids from vents (tenth
      from chemosynthetic ecosystems), and extend the distribution of both species to
      the southwest. Neither family has been recorded at chemosynthetic ecosystems in
      the western Pacific. Both were from weakly diffuse flow areas not subject to high
      temperature venting but were nevertheless associated with typical vent-reliant
      taxa such as Lamellibrachia tubeworms and Bathymodiolus mussels. These new
      records show that these species are capable of tolerating environmental stress
      associated with weak hydrothermally influenced areas, despite not being vent
      endemic species, adding to the list of known vent/non-vent species intersections.
      This signifies that such weakly influenced areas may provide key habitats for
      them, and that such areas may play a role in the evolution of biological
      adaptations to 'extreme' chemosynthetic ecosystems.

PMID- 29209580
TI  - The pht4;1-3 mutant line contains a loss of function allele in the Fatty Acid
      Desaturase 7 gene caused by a remnant inactivated selection marker-a cautionary
      tale.
AB  - A striking and unexpected biochemical phenotype was found in an insertion mutant
      line in the model plant Arabidopsis thaliana. One of two investigated insertion
      mutant lines in the gene encoding the phosphate transporter PHT4;1 demonstrated a
      prominent loss of trienoic fatty acids, whereas the other insertion line was
      indistinguishable from wild type in this aspect. We demonstrate that the loss of
      trienoic fatty acids was due to a remnant inactive negative selection marker gene
      in this particular transposon tagged line, pht4;1-3. This constitutes a
      cautionary tale that warns of the importance to confirm the loss of this type of
      selection markers and the importance of verifying the relationship between a
      phenotype and genotype by more than one independent mutant line or alternatively
      genetic complementation.

PMID- 29209573
TI  - Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.
AB  - The expression "immunogenic cell death" (ICD) refers to a functionally unique
      form of cell death that facilitates (instead of suppressing) a T cell-dependent
      immune response specific for dead cell-derived antigens. ICD critically relies on
      the activation of adaptive responses in dying cells, culminating with the
      exposure or secretion of immunostimulatory molecules commonly referred to as
      "damage-associated molecular patterns". Only a few agents can elicit bona fide
      ICD, including some clinically established chemotherapeutics such as doxorubicin,
      epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and
      oxaliplatin. In this Trial Watch, we discuss recent progress on the development
      of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate
      clinical efficacy in conjunction with immunological biomarkers.

PMID- 29209575
TI  - Trial watch: DNA-based vaccines for oncological indications.
AB  - DNA-based vaccination is a promising approach to cancer immunotherapy. DNA-based
      vaccines specific for tumor-associated antigens (TAAs) are indeed relatively
      simple to produce, cost-efficient and well tolerated. However, the clinical
      efficacy of DNA-based vaccines for cancer therapy is considerably limited by
      central and peripheral tolerance. During the past decade, considerable efforts
      have been devoted to the development and characterization of novel DNA-based
      vaccines that would circumvent this obstacle. In this setting, particular
      attention has been dedicated to the route of administration, expression of
      modified TAAs, co-expression of immunostimulatory molecules, and co-delivery of
      immune checkpoint blockers. Here, we review preclinical and clinical progress on
      DNA-based vaccines for cancer therapy.

PMID- 29209581
TI  - Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive
      Disorder.
AB  - Major depressive disorder (MDD) is a disorder that carries significant
      psychosocial and economic implications. Research efforts have focused on
      identifying biomarkers that can aid in the prediction, diagnosis, and efficacious
      treatment of MDD. Most of this focus has been placed on a polymorphism of the
      methylenetetrahydrofolate reductase (MTHFR) gene, C677T. MTHFR C677T is screened
      during MDD diagnosis in many protocols. However, MTHFR C667T poses conflicting
      data in various ethnic groups and geographic populations calling into question
      its utility. Another polymorphism, MTHFR A1298C, has often taken the back-seat to
      MTHFR C677T in respect to research focus. MTHFR A1298C is implicated in irregular
      homocysteine metabolism and aberrant folate cycles and, through this, it may play
      a role as either a driver in the development of MDD or as a predictive or
      diagnostic marker, possibly in combination with C677T. The number of studies
      evaluating MTHFR A1298C and the power of those studies is lacking and thus larger
      studies are required to confirm the association between this polymorphism and
      MDD.

PMID- 29209582
TI  - White Matter Tracts in Patients with Temporal Lobe Epilepsy: Pre- and
      Postoperative Assessment.
AB  - Patients with intractable temporal lobe epilepsy (TLE) undergo surgical resection
      of the anterior temporal lobe. Preoperative assessment of TLE patients involves a
      multidisciplinary assessment and may involve the use of invasive
      electroencephalogram (EEG) recording for lateralization of seizure focus in
      ambiguous cases. Understanding the white matter fibre tracts affected in TLE may
      assist in preoperative lateralization and planning. We studied pre- and
      postoperative white matter fibre tract changes in six patients with TLE who
      underwent surgical resection. Our results indicate that changes in the corpus
      callosum are highly specific, with the ability to lateralize the epileptogenic
      side in 100% of our patients (six of six). Contralateral changes were found in
      all patients with variable involvement of white matter tracts. Postoperatively,
      most patients (five of six) exhibited further changes to the tracts on the
      ipsilateral side, with three patients showing contralateral abnormalities. We
      provide a detailed assessment of pre- and postoperative white matter fibre tracts
      in patients with TLE and confirm that abnormalities in the ipsilateral corpus
      callosum may aid in preoperative lateralization and obviate the need for invasive
      EEG monitoring.

PMID- 29209583
TI  - What Makes the Optimal Wound Healing Material? A Review of Current Science and
      Introduction of a Synthetic Nanofabricated Wound Care Scaffold.
AB  - Wound matrix materials are used to improve the regeneration of dermal and
      epidermal layers in both acute and chronic wounds. Contemporary wound matrices
      are primarily composed of biologic materials such as processed xenogeneic and
      allogeneic tissues. Unfortunately, existing biologic wound matrices possess
      multiple limitations including poor longevity, durability, strength, and
      enzymatic resistance required for persistent support for new tissue formation. A
      fully-synthetic, resorbable electrospun material (Restrata Wound Matrix, Acera,
      St.Louis, Missouri ) that exhibits structural similarities to the native
      extracellular matrix offers a new approach to the treatment of acute and chronic
      wounds. This novel matrix is the first product to combine the advantages of
      synthetic construction (e.g. resistance to enzymatic degradation, excellent
      biocompatibility, strength/durability and controlled degradation) with the
      positive attributes of biologic materials (e.g. biomimetic architecture similar
      to human extracellular matrix (ECM), fibrous architecture optimized to support
      cellular migration and proliferation, engineered porosity to encourage tissue
      ingrowth and vascularization). These features allow RWM to achieve rapid and
      complete healing of full-thickness wounds that, in preclinical studies, is
      comparable to Integra Bilayer Wound Matrix (Integra LifeSciences, Plainsboro, New
      Jersey), a gold standard biologic material with diverse clinical indications in
      the wound care. Together, this review suggests that the RWM offers a unique fully
      synthetic alternative to existing biologic matrices that is effective, widely
      available, easy to store, simple to apply and low cost.

PMID- 29209584
TI  - Sudden Death from Spontaneous Coronary Artery Dissection due to Polyarteritis
      Nodosa.
AB  - Spontaneous coronary artery dissection (SCAD) is an emerging and rare cause of
      acute coronary syndrome and sudden cardiac death. While it was previously
      reported among young females with fibromuscular dysplasia, new literature
      indicates that this condition could occur in older populations. Polyarteritis
      nodosa (PAN) causes systemic necrotizing vasculitis which typically affects small
      to medium-sized muscular arteries and could affect the coronary arteries. A few
      case reports of PAN causing acute coronary artery disease have been reported in
      the literature. We report a case of a 62-year-old lady who presented with
      abdominal pain and died abruptly during her stay; she was found to have PAN
      associated SCAD on autopsy.

PMID- 29209585
TI  - Video Microscope Robotic Arm-Assisted, Neuronavigation-guided Glioma Resection
      and Regional Sampling.
AB  - High-grade gliomas possess internal pathological heterogeneity. Selective
      sampling of different tumor regions can help in the study of this heterogeneity.
      In this report, we have described the use of a novel navigation and optical
      system for the selective regional sampling of a high-grade glioma lesion. A 45
      year-old gentleman presented to us with complaints of intermittent frontal
      headaches for past eight months. On examination, he had subtle pyramidal weakness
      in left upper and lower extremities. Magnetic resonance imaging (MRI) showed a
      large contrast-enhancing, space-occupying lesion in the right frontal lobe
      causing perilesional edema and midline shift. We marked four different regions on
      the preoperative MRI using apparent diffusion coefficient (ADC) mapping and
      contrast enhancement pattern in four different combinations using presurgical
      planning software (BrightMatterTM Plan) (Synaptive Medical, Inc., Toronto,
      Canada). These pre-identified areas were exported into BrightMatterTM Servo
      (Synaptive Medical, Toronto, Canada), an integrated robotic video microscope with
      a neuronavigation system where these areas were selectively sampled and sent for
      analysis. The BrightMatterTM Servo not only helped us to the target areas but
      also helped to identify a safe trajectory, respecting white matter tracts.
      Histopathology showed a neoplastic lesion composed of mononuclear round cells
      with the perinuclear halo in a fibrillary stroma with admixed mini-gemistocytes
      consistent with the diagnosis of a Grade 3 anaplastic astrocytoma. A selective
      regional sampling of the gliomas can be reliably performed using BrightMatterTM
      technologies to study the pathological heterogeneity of these lesions.

PMID- 29209586
TI  - Diffusion-tensor Imaging and Tractography Application in Pre-operative Planning
      of Intra-axial Brain Lesions.
AB  - Gliomas are the most common brain tumors that diffusely infiltrate the
      surrounding white matter (WM) tracts. Conventional MRI is commonly used for tumor
      localization and characterization. However, this does not give precise
      information about the WM infiltration surrounding the tumor. Diffusion-tensor
      imaging (DTI) is a non-invasive magnetic resonance (MR) technique that measures
      WM tissue integrity and tractography (fiber tracking) used to investigate the
      preferential directionality of diffusion. DTI allows visualization of WM tracts
      in the immediate vicinity of brain tumors that permit maximum tumor resection
      while also preserving the eloquent brain areas. The relation of tumors with the
      white matter tracts (deviation, infiltration, and disruption) has been one the
      most important initial applications of DTI. The fibers can be infiltrated in
      normal-appearing areas, and abnormal-appearing areas of the brain can show
      anatomically intact fibers. In the surgical planning of brain tumors, surgery is
      aided by knowing the proximity and relative position of the tumor to the adjacent
      WM tracts. The aim of the present study is to assess the role of DT tractography
      (DTT) in preoperative mapping of major WM tracts in relation to brain tumors.

PMID- 29209587
TI  - Effect of Treating Depressive Disorders on Mortality of Cancer Patients.
AB  - Depression can have debilitating effects on patients with a chronic morbid
      disease, in particular, cancer. It has been found that patients with a depressive
      disorder have a poorer prognosis and increased mortality. There is a debate as to
      whether the treatment of the depressive disorder is beneficial to these patients.
      Studies demonstrate varying results with pharmacotherapy and behavioral therapy.
      All cancer patients should be periodically assessed for depressive disorder and
      the symptoms not dismissed as part of their cancer presentation due to the
      increased mortality.

PMID- 29209588
TI  - Efficient genetic transformation of Momordica charantia L. by microprojectile
      bombardment.
AB  - Here, we report the optimized conditions for biolistic particle delivery-mediated
      genetic transformation of bitter melon using petiole segments. In this study, DNA
      coated gold particles of 0.6 um were used for optimizing the parameters of
      transformation and eventually regeneration of bitter melon putative transgenics.
      Initially, biolistic parameters namely helium pressure and macrocarrier to target
      tissue distance, were optimized using binary vector pBI121 carrying both beta
      glucuronidase gene (GUS) and neomycin phosphotransferase II gene (npt II) as a
      reporter and as a selectable marker gene, respectively. The effect of optimized
      physical parameters on the frequency of transient (79.2 +/- 1.52%) and stable
      (41.9%) expressions has been investigated. The optimized biolistic parameters for
      petiole segments of Momordica charantia L. were determined as follows: 650 psi
      helium pressure and 6 cm target distance. Using the optimized parameters,
      transformation of bitter melon was carried out for generation of putative
      transformants from bombarded tissues on SRM-K medium, with a mean number of 50.3
      explants surviving at the end of the final selection (50 mg l-1 kanamycin) round.
      Finally, the transformants produced were subjected to GUS histochemical assay,
      and integration of the transgenes (GUS and npt II) into the nuclear genome was
      confirmed by PCR analysis. DNA blot analysis confirmed the transgene integration
      in the transformed plantlet genomes. The present study may be used for developing
      transplastomic technology in this valuable medicinal plant for enhanced metabolic
      engineering pathways and production of biopharmaceuticals.

PMID- 29209591
TI  - Commentary: Molecular Machines Open Cell Membranes.

PMID- 29209590
TI  - Risk factors for community-acquired pneumonia among adults in Kenya: a case
      control study.
AB  - Background: Pneumonia is a leading cause of morbidity and mortality among adults
      worldwide; however, the risk factors for community-acquired pneumonia in Africa
      are not well characterized. Methods: The authors recruited 281 cases of community
      acquired pneumonia and 1202 hospital controls among patients aged >=15 years who
      attended Kilifi District Hospital/Coast Provincial General Hospital in Kenya
      between 1994 and 6. Cases were admissions with an acute illness with >=2
      respiratory signs and evidence of consolidation on a chest radiograph. Controls
      were patients without signs of pneumonia, frequency matched by age, sex and
      hospital. Risk factors related to socio-demographic factors, drug use, clinical
      history, contact patterns and exposures to indoor air pollution were investigated
      by questionnaire, anthropometric measurements and laboratory assays. Associations
      were evaluated using a hierarchical logistic regression model. Results: Pneumonia
      was associated with human immunodeficiency virus (HIV) infection (Odds Ratio [OR]
      2.06, 95% CI 1.44-3.08), anemia (OR 1.91, 1.31-2.74), splenomegaly (OR 2.04, 95%
      CI 1.14-3.41), recent history of pneumonia (OR 4.65, 95% CI 1.66-12.5), history
      of pneumonia >2 years previously (OR 17.13, 95% CI 5.01-60.26), coryza in the 2
      weeks preceding hospitalization (OR 2.09, 95% CI 1.44-3.03), current smoking
      (2.19, 95% CI 1.39-3.70), use of khat (OR 3.44, 95% CI 1.72-7.15), use of snuff
      (OR 2.67, 95% CI 1.35-5.49) and contact with several animal species. Presence of
      a Bacillus Calmette-Guerin (BCG) scar was associated with protection (OR 0.51,
      95% CI 0.32-0.82). The risk factors varied significantly by sex. Conclusion:
      Pneumonia in Kenyan adults was associated with global risk factors, such as HIV
      and smoking, but also with specific local factors like drug use and contact with
      animals. Intervention strategies should account for sex-specific differences in
      risk factors.

PMID- 29209592
TI  - Increased Expression of a MicroRNA Correlates with Anthelmintic Resistance in
      Parasitic Nematodes.
AB  - Resistance to anthelmintic drugs is a major problem in the global fight against
      parasitic nematodes infecting humans and animals. While previous studies have
      identified mutations in drug target genes in resistant parasites, changes in the
      expression levels of both targets and transporters have also been reported. The
      mechanisms underlying these changes in gene expression are unresolved. Here, we
      take a novel approach to this problem by investigating the role of small
      regulatory RNAs in drug resistant strains of the important parasite Haemonchus
      contortus. microRNAs (miRNAs) are small (22 nt) non-coding RNAs that regulate
      gene expression by binding predominantly to the 3' UTR of mRNAs. Changes in miRNA
      expression have been implicated in drug resistance in a variety of tumor cells.
      In this study, we focused on two geographically distinct ivermectin resistant
      strains of H. contortus and two lines generated by multiple rounds of
      backcrossing between susceptible and resistant parents, with ivermectin
      selection. All four resistant strains showed significantly increased expression
      of a single miRNA, hco-miR-9551, compared to the susceptible strain. This same
      miRNA is also upregulated in a multi-drug-resistant strain of the related
      nematode Teladorsagia circumcincta. hco-miR-9551 is enriched in female worms, is
      likely to be located on the X chromosome and is restricted to clade V parasitic
      nematodes. Genes containing predicted binding sites for hco-miR-9551 were
      identified computationally and refined based on differential expression in a
      transcriptomic dataset prepared from the same drug resistant and susceptible
      strains. This analysis identified three putative target mRNAs, one of which, a
      CHAC domain containing protein, is located in a region of the H. contortus genome
      introgressed from the resistant parent. hco-miR-9551 was shown to interact with
      the 3' UTR of this gene by dual luciferase assay. This study is the first to
      suggest a role for miRNAs and the genes they regulate in drug resistant parasitic
      nematodes. miR-9551 also has potential as a biomarker of resistance in different
      nematode species.

PMID- 29209594
TI  - Genome-Wide Search for Competing Endogenous RNAs Responsible for the Effects
      Induced by Ebola Virus Replication and Transcription Using a trVLP System.
AB  - Understanding how infected cells respond to Ebola virus (EBOV) and how this
      response changes during the process of viral replication and transcription are
      very important for establishing effective antiviral strategies. In this study, we
      conducted a genome-wide screen to identify long non-coding RNAs (lncRNAs),
      circular RNAs (circRNAs), micro RNAs (miRNAs), and mRNAs differentially expressed
      during replication and transcription using a tetracistronic transcription and
      replication-competent virus-like particle (trVLP) system that models the life
      cycle of EBOV in 293T cells. To characterize the expression patterns of these
      differentially expressed RNAs, we performed a series cluster analysis, and up- or
      down-regulated genes were selected to establish a gene co-expression network.
      Competing endogenous RNA (ceRNA) networks based on the RNAs responsible for the
      effects induced by EBOV replication and transcription in human cells, including
      circRNAs, lncRNAs, miRNAs, and mRNAs, were constructed for the first time. Based
      on these networks, the interaction details of circRNA-chr19 were explored. Our
      results demonstrated that circRNA-chr19 targeting miR-30b-3p regulated CLDN18
      expression by functioning as a ceRNA. These findings may have important
      implications for further studies of the mechanisms of EBOV replication and
      transcription. These RNAs potentially have important functions and may be
      promising targets for EBOV therapy.

PMID- 29209593
TI  - Analysis of the Salivary Gland Transcriptome of Unfed and Partially Fed Amblyomma
      sculptum Ticks and Descriptive Proteome of the Saliva.
AB  - Ticks are obligate blood feeding ectoparasites that transmit a wide variety of
      pathogenic microorganisms to their vertebrate hosts. Amblyomma sculptum is vector
      of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever
      (RMSF), the most lethal rickettsiosis that affects humans. It is known that the
      transmission of pathogens by ticks is mainly associated with the physiology of
      the feeding process. Pathogens that are acquired with the blood meal must first
      colonize the tick gut and later the salivary glands (SG) in order to be
      transmitted during a subsequent blood feeding via saliva. Tick saliva contains a
      complex mixture of bioactive molecules with anticlotting, antiplatelet
      aggregation, vasodilatory, anti-inflammatory, and immunomodulatory properties to
      counteract both the hemostasis and defense mechanisms of the host. Besides
      facilitating tick feeding, the properties of saliva may also benefits survival
      and establishment of pathogens in the host. In the current study, we compared the
      sialotranscriptome of unfed A. sculptum ticks and those fed for 72 h on rabbits
      using next generation RNA sequencing (RNA-seq). The total of reads obtained were
      assembled in 9,560 coding sequences (CDSs) distributed in different functional
      classes. CDSs encoding secreted proteins, including lipocalins, mucins, protease
      inhibitors, glycine-rich proteins, metalloproteases, 8.9 kDa superfamily members,
      and immunity-related proteins were mostly upregulated by blood feeding. Selected
      CDSs were analyzed by real-time quantitative polymerase chain reaction preceded
      by reverse transcription (RT-qPCR), corroborating the transcriptional profile
      obtained by RNA-seq. Finally, high-performance liquid chromatography coupled with
      tandem mass spectrometry (LC-MS/MS) analysis revealed 124 proteins in saliva of
      ticks fed for 96-120 h. The corresponding CDSs of 59 of these proteins were
      upregulated in SG of fed ticks. To the best of our knowledge, this is the first
      report on the proteome of A. sculptum saliva. The functional characterization of
      the identified proteins might reveal potential targets to develop vaccines for
      tick control and/or blocking of R. rickettsii transmission as well as
      pharmacological bioproducts with antihemostatic, anti-inflammatory and
      antibacterial activities.

PMID- 29209596
TI  - AFLP reveals low genetic diversity of the bryozoan Pectinatella magnifica (Leidy,
      1851) in the Czech Republic.
AB  - Background: Non-native species have aroused scientific interest because of their
      ability to successfully colonise areas to which they have been introduced,
      despite their sometimes limited genetic variation compared to their native range.
      These species establish themselves with the aid of some pre-existing features
      favouring them in the new environment. Pectinatella magnifica (Leidy, 1851), the
      freshwater magnificent bryozoan, is non-native in Europe and Asia. This study was
      designed to determine the genetic diversity and population structure of P.
      magnifica colonies collected from the Protected Landscape Area (PLA) and UNESCO
      Biosphere Reserve Trebonsko (the Czech Republic) in the 2009 and 2011-2014
      periods using Amplified Fragment Length Polymorphism (AFLP). Findings: The vast
      majority of the examined non-native colonies, except three colonies sampled in
      2012, expressed very low levels of genetic variation, not differentiating from
      the USA native colony. The Bayesian clustering approach grouped the 28 accessions
      into two genetically different populations. Conclusions: The data suggest
      relatively low gene diversity within all colonies, which might reflect the recent
      expansion of P. magnifica in the Czech Republic.

PMID- 29209595
TI  - Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology,
      Hypervirulence-Associated Determinants, and Resistance Mechanisms.
AB  - Klebsiella pneumoniae is one of the most clinically relevant species in
      immunocompromised individuals responsible for community-acquired and nosocomial
      infections, including pneumonias, urinary tract infections, bacteremias, and
      liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally
      associated with the hypermucoviscosity phenotype, has emerged as a clinically
      significant pathogen responsible for serious disseminated infections, such as
      pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally
      younger and healthier population. Hypervirulent K. pneumoniae infections were
      primarily found in East Asia and now are increasingly being reported worldwide.
      Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible,
      some isolates with combined virulence and resistance, such as the carbapenem
      resistant hypervirulent K. pneumoniae isolates, are increasingly being detected.
      The combination of multidrug resistance and enhanced virulence has the potential
      to cause the next clinical crisis. To better understand the basic biology of
      hypervirulent K. pneumoniae, this review will provide a summarization and
      discussion focused on epidemiology, hypervirulence-associated factors, and
      antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological
      analysis of recent clinical isolates in China warns the global dissemination of
      hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the
      near future. Therefore, an immediate response to recognize the global
      dissemination of this hypervirulent strain with resistance determinants is an
      urgent priority.

PMID- 29209598
TI  - Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in
      a Randomized Trial of Permissive Hypercapnia.
AB  - Background: Ventilator-induced lung injury is considered to be a main factor in
      the pathogenesis of bronchopulmonary dysplasia (BPD). Optimizing ventilator
      strategies may reduce respiratory morbidities in preterm infants. Permissive
      hypercapnia has been suggested to attenuate lung injury. We aimed to determine if
      a higher PCO2 target range results in less lung injury compared to the control
      target range and possibly reduces pro-inflammatory cytokines and acid
      sphingomyelinase (ASM) in tracheal aspirates (TA), which has not been addressed
      before. Methods: During a multicenter trial of permissive hypercapnia in
      extremely low birthweight infants (PHELBI), preterm infants (birthweight 400
      1,000 g, gestational age 23 0/7-28 6/7 weeks) requiring mechanical ventilation
      within 24 h of birth were randomly assigned to a high PCO2 target or a control
      group. The high target group aimed at PCO2 values of 55-65, 60-70, and 65-75 mmHg
      and the control group at PCO2 values of 40-50, 45-55 and 50-60 mmHg on postnatal
      days 1-3, 4-6, and 7-14, respectively. TA was analyzed for pro-inflammatory
      cytokines from postnatal day 2-21. BPD was determined at a postmenstrual age of
      36 weeks +/- 2 days. Main findings: Levels of inflammatory cytokines and ASM were
      similar in both groups: interleukin (IL)-6 (p = 0.14), IL-8 (p = 0.43), IL-10 (p
      = 0.24), IL-1beta (p = 0.11), macrophage inflammatory protein 1alpha (p = 0.44),
      albumin (p = 0.41), neuropeptide Y (p = 0.52), leukotriene B4 (p = 0.11),
      transforming growth factor-beta1 (p = 0.68), nitrite (p = 0.15), and ASM (p =
      0.94). Furthermore, most inflammatory mediators were strongly affected by the age
      of the infants and increased from postnatal day 2 to 21. BPD or death was
      observed in 14 out of 62 infants, who were distributed evenly between both
      groups. Conclusion: The results suggest that high PCO2 target levels did not
      result in lower pulmonary inflammatory activity and thus reflect clinical
      results. This indicates that high PCO2 target ranges are not effective in
      reducing ventilator-induced lung injury in preterm infants, as compared to
      control targets. Trial registration: ISRCTN56143743.

PMID- 29209597
TI  - Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research
      Advances.
AB  - Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly
      syndrome caused by mutations in genes encoding proteins that are structural or
      functional components of the primary cilium. Conditions that are caused by
      mutations in ciliary genes are collectively termed the ciliopathies, and MKS
      represents the most severe condition in this group of disorders. The primary
      cilium is a microtubule-based organelle, projecting from the apical surface of
      vertebrate cells. It acts as an "antenna" that receives and transduces
      chemosensory and mechanosensory signals, but also regulates diverse signaling
      pathways, such as Wnt and Shh, that have important roles during embryonic
      development. Most MKS proteins localize to a distinct ciliary compartment called
      the transition zone (TZ) that regulates the trafficking of cargo proteins or
      lipids. In this review, we provide an up-to-date summary of MKS clinical
      features, molecular genetics, and clinical diagnosis. MKS has a highly variable
      phenotype, extreme genetic heterogeneity, and displays allelism with other
      related ciliopathies such as Joubert syndrome, presenting significant challenges
      to diagnosis. Recent advances in genetic technology, with the widespread use of
      multi-gene panels for molecular testing, have significantly improved diagnosis,
      genetic counseling, and the clinical management of MKS families. These include
      the description of some limited genotype-phenotype correlations. We discuss
      recent insights into the molecular basis of disease in MKS, since the functions
      of some of the relevant ciliary proteins have now been determined. A common
      molecular etiology appears to be disruption of ciliary TZ structure and function,
      affecting essential developmental signaling and the regulation of secondary
      messengers.

PMID- 29209599
TI  - Static and Dynamic Ultrasound Imaging to Visualize the Bladder, Bladder Neck,
      Urethra, and Pelvic Floor in Children with Daytime Incontinence.

PMID- 29209601
TI  - Information Quality Challenges of Patient-Generated Data in Clinical Practice.
AB  - A characteristic trend of digital health has been the dramatic increase in
      patient-generated data being presented to clinicians, which follows from the
      increased ubiquity of self-tracking practices by individuals, driven, in turn, by
      the proliferation of self-tracking tools and technologies. Such tools not only
      make self-tracking easier but also potentially more reliable by automating data
      collection, curation, and storage. While self-tracking practices themselves have
      been studied extensively in human-computer interaction literature, little work
      has yet looked at whether these patient-generated data might be able to support
      clinical processes, such as providing evidence for diagnoses, treatment
      monitoring, or postprocedure recovery, and how we can define information quality
      with respect to self-tracked data. In this article, we present the results of a
      literature review of empirical studies of self-tracking tools, in which we
      identify how clinicians perceive quality of information from such tools. In the
      studies, clinicians perceive several characteristics of information quality
      relating to accuracy and reliability, completeness, context, patient motivation,
      and representation. We discuss the issues these present in admitting self-tracked
      data as evidence for clinical decisions.

PMID- 29209600
TI  - Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia.
AB  - Acute myeloid leukemia (AML) is the second most common leukemia of childhood and
      is associated with high rates of chemotherapy resistance and relapse. Clinical
      outcomes for children with AML treated with maximally intensive multi-agent
      chemotherapy lag far behind those of children with the more common acute
      lymphoblastic leukemia, demonstrating continued need for new therapeutic
      approaches to decrease relapse risk and improve long-term survival. Mutations in
      the FMS-like tyrosine kinase-3 receptor gene (FLT3) occur in approximately 25% of
      children and adults with AML and are associated with particularly poor prognoses.
      Identification and development of targeted FLT3 inhibitors represents a major
      precision medicine paradigm shift in the treatment of patients with AML. While
      further development of many first-generation FLT3 inhibitors was hampered by
      limited potency and significant toxicity due to effects upon other kinases, the
      more selective second- and third-generation FLT3 inhibitors have demonstrated
      excellent tolerability and remarkable efficacy in the relapsed/refractory and now
      de novo FLT3-mutated AML settings. While these newest and most promising
      inhibitors have largely been studied in the adult population, pediatric
      investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing
      or planned. Successful development of FLT3 inhibitor-based therapies will be
      essential to improve outcomes in children with this high-risk subtype of AML.

PMID- 29209602
TI  - Economic Evaluation and Budget Impact Analysis of Vaccination against Haemophilus
      influenzae Type b Infection in Thailand.
AB  - Current study aimed to estimate clinical and economic outcomes of providing the
      Haemophilus influenzae type b (Hib) vaccination as a national vaccine
      immunization program in Thailand. A decision tree combined with Markov model was
      developed to simulate relevant costs and health outcomes covering lifetime
      horizon in societal and health care payer perspectives. This analysis considered
      children aged under 5 years old whom preventive vaccine of Hib infection are
      indicated. Two combined Hib vaccination schedules were considered: three-dose
      series (3 + 0) and three-dose series plus a booster does (3 + 1) compared with no
      vaccination. Budget impact analysis was also performed under Thai government
      perspective. The outcomes were reported as Hib-infected cases averted and
      incremental cost-effectiveness ratios (ICERs) in 2014 Thai baht (THB) ($) per
      quality-adjusted life year (QALY) gained. In base-case scenario, the model
      estimates that 3,960 infected cases, 59 disability cases, and 97 deaths can be
      prevented by national Hib vaccination program. The ICER for 3 + 0 schedule was
      THB 1,099 ($34) per QALY gained under societal perspective. The model was
      sensitive to pneumonia incidence among aged under 5 years old and direct non
      medical care cost per episode of Hib pneumonia. Hib vaccination is very cost
      effective in the Thai context. The budget impact analysis showed that Thai
      government needed to invest an additional budget of 110 ($3.4) million to
      implement Hib vaccination program. Policy makers should consider our findings for
      adopting this vaccine into national immunization program.

PMID- 29209603
TI  - Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and
      Pitfalls in Research and Practice.
AB  - Within the context of screening tests, it is important to avoid misconceptions
      about sensitivity, specificity, and predictive values. In this article,
      therefore, foundations are first established concerning these metrics along with
      the first of several aspects of pliability that should be recognized in relation
      to those metrics. Clarification is then provided about the definitions of
      sensitivity, specificity, and predictive values and why researchers and
      clinicians can misunderstand and misrepresent them. Arguments are made that
      sensitivity and specificity should usually be applied only in the context of
      describing a screening test's attributes relative to a reference standard; that
      predictive values are more appropriate and informative in actual screening
      contexts, but that sensitivity and specificity can be used for screening
      decisions about individual people if they are extremely high; that predictive
      values need not always be high and might be used to advantage by adjusting the
      sensitivity and specificity of screening tests; that, in screening contexts,
      researchers should provide information about all four metrics and how they were
      derived; and that, where necessary, consumers of health research should have the
      skills to interpret those metrics effectively for maximum benefit to clients and
      the healthcare system.

PMID- 29209604
TI  - Development of All India Institute of Medical Sciences-Modified International
      Clinical Epidemiology Network Diagnostic Instrument for Neuromotor Impairments in
      Children Aged 1 Month to 18 Years.
AB  - Introduction: There is shortage of specialists for the diagnosis of children with
      neuromotor impairments (NMIs), especially in resource limited settings. Existing
      International Clinical Epidemiology Network (INCLEN) instrument for diagnosing
      NMI have been validated for children aged 2-9 years. The current study modified
      the same including wider symptomatology and age group (1 month to 18 years).
      Methods: The Modified INCLEN diagnostic tool (INDT) was developed by a team of
      experts by modifying the existing tool to widen the age range (1 month to 18
      years) and include broader symptomatology (inclusion of milestones from the first
      2 years of life and better elucidation of cerebellar and extrapyramidal features)
      in a tertiary care teaching hospital of North India between January and April
      2015. A trained medical graduate applied the candidate tool, which was followed
      by gold standard evaluation by a Pediatric Neurologist (both blinded to each
      other). Results: A total of 197 children (102 with NMI and 95 without NMI) were
      enrolled for the study. The sensitivity, specificity, positive and negative
      predictive values, positive and negative likelihood ratio of the modified NMI
      tool were 90.4% (82.6-95.5), 95.5% (88.7-98.7), 95.5% (88.9-98.7), 90.3% (82.4
      95.5), 19.9 (12.1-32.6), and 0.13 (0.08-0.12), respectively. Conclusion: The All
      India Institute of Medical Sciences modified INDT NMI tool is a simple and
      structured instrument covering a wider symptomatology in the 1 month to 18 years
      age group with acceptable diagnostic accuracy.

PMID- 29209605
TI  - The Effect of Cigarette Smoking during Pregnancy on Endocrine Pancreatic Function
      and Fetal Growth: A Pilot Study.
AB  - Introduction: Cigarette smoking in pregnancy is a common cause of fetal growth
      restriction. We aimed to investigate endocrine pancreatic function of mother
      infant dyads in relation to cigarette smoking, as a possible mechanism for the
      poor fetal growth. Methods: Prospective study of smoking mothers (10 cigarettes
      or more per day, self-reported to the midwife) and non-smoker control mothers
      during their first pregnancy. Insulin, glucose, C-peptide, HbA1C, fructosamine,
      prolactin, serotonin, and cortisol were measured in maternal blood at 24-26 weeks
      and in umbilical cord blood at birth. Cotinine was also measured in cord blood.
      Results: Of 37 smokers and 36 non-smokers recruited, cord blood was obtainable
      from 38 babies (19 in each group). In utero cigarette exposure was associated
      with lower birthweight (3,035 +/- 490 versus 3,405 +/- 598 g, p = 0.005), with
      linear modeling of the smoking cohort showing a 41 g reduction for every increase
      of one cigarette smoked per day (95% CI -71 to -11 g, p = 0.010). There were no
      differences between groups in indices of maternal or perinatal endocrine
      pancreatic dysfunction. Heavier smoking independently correlated with higher
      maternal fasting levels of glucose (p = 0.044) and C-peptide (p = 0.011). We did
      not observe any significant associations between the daily number of cigarettes
      and any of the cord blood parameters. We also looked for differences between
      cohorts based on infant gender. Serotonin levels were higher in smoking mothers
      with male fetuses (p = 0.01 to p = 0.004). Conclusion: Endocrine pancreatic
      dysfunction does not appear to be a major contributing factor to nicotine
      associated fetal growth restriction. The higher serotonin levels in smoking
      mothers carrying male infants is of uncertain significance but could be a
      manifestation of gender differences in susceptibility to the long-term effects of
      cigarette smoking.

PMID- 29209606
TI  - Carbon Domains on MoS2/TiO2 System via Catalytic Acetylene Oligomerization:
      Synthesis, Structure, and Surface Properties.
AB  - Carbon domains have been obtained at the surface of a MoS2/TiO2 (Evonik, P25)
      system via oligomerization and cyclotrimerization reactions involved in the
      interaction of the photoactive material with acetylene. Firstly, MoS2 nanosheets
      have been synthesized at the surface of TiO2, via sulfidation of a molybdenum
      oxide precursor with H2S (bottom-up method). Secondly, the morphology and the
      structure, the optical and the vibrational properties of the obtained materials,
      for each step of the synthesis procedure, have been investigated by microscopy
      and spectroscopy methods. In particular, transmission electron microscopy images
      provide a simple tool to highlight the effectiveness of the sulfidation process,
      thus showing 1L, 2L, and stacked MoS2 nanosheets anchored to the surface of TiO2
      nanoparticles. Lastly, in-situ FTIR spectroscopy investigation gives insights
      into the nature of the oligomerized species, showing that the formation of both
      polyenic and aromatic systems can be taken into account, being their formation
      promoted by both Ti and Mo catalytic sites. This finding gives an opportunity for
      the assembly of extended polyenic, polyaromatic, or mixed domains firmly attached
      at the surface of photoactive materials. The presented approach, somehow
      different from the carbon adding or doping processes of TiO2, is of potential
      interest for the advanced green chemistry and energy conversion/transport
      applications.

PMID- 29209608
TI  - Synthesis of Zr2WP2O12/ZrO2 Composites with Adjustable Thermal Expansion.
AB  - Zr2WP2O12/ZrO2 composites were fabricated by solid state reaction with the goal
      of tailoring the thermal expansion coefficient. XRD, SEM and TMA were used to
      investigate the composition, microstructure, and thermal expansion behavior of
      Zr2WP2O12/ZrO2 composites with different mass ratio. Relative densities of all
      the resulting Zr2WP2O12/ZrO2 samples were also tested by Archimedes' methods. The
      obtained Zr2WP2O12/ZrO2 composites were comprised of orthorhombic Zr2WP2O12 and
      monoclinic ZrO2. As the increase of the Zr2WP2O12, the relative densities of
      Zr2WP2O12/ZrO2 ceramic composites increased gradually. The coefficient of thermal
      expansion of the Zr2WP2O12/ZrO2 composites can be tailored from 4.1 * 10-6 K-1 to
      -3.3 * 10-6 K-1 by changing the content of Zr2WP2O12. The 2:1 Zr2WP2O12/ZrO2
      specimen shows close to zero thermal expansion from 25 to 700 degrees C with an
      average linear thermal expansion coefficient of -0.09 * 10-6 K-1. These
      adjustable and near zero expansion ceramic composites will have great potential
      application in many fields.

PMID- 29209609
TI  - Culture Medium Supplements Derived from Human Platelet and Plasma: Cell
      Commitment and Proliferation Support.
AB  - Present cell culture medium supplements, in most cases based on animal sera, are
      not fully satisfactory especially for the in vitro expansion of cells intended
      for human cell therapy. This paper refers to (i) an heparin-free human platelet
      lysate (PL) devoid of serum or plasma components (v-PL) and (ii) an heparin-free
      human serum derived from plasma devoid of PL components (Pl-s) and to their use
      as single components or in combination in primary or cell line cultures. Human
      mesenchymal stem cells (MSC) primary cultures were obtained from adipose tissue,
      bone marrow, and umbilical cord. Human chondrocytes were obtained from articular
      cartilage biopsies. In general, MSC expanded in the presence of Pl-s alone showed
      a low or no proliferation in comparison to cells grown with the combination of Pl
      s and v-PL. Confluent, growth-arrested cells, either human MSC or human articular
      chondrocytes, treated with v-PL resumed proliferation, whereas control cultures,
      not supplemented with v-PL, remained quiescent and did not proliferate.
      Interestingly, signal transduction pathways distinctive of proliferation were
      activated also in cells treated with v-PL in the absence of serum, when cell
      proliferation did not occur, indicating that v-PL could induce the cell re-entry
      in the cell cycle (cell commitment), but the presence of serum proteins was an
      absolute requirement for cell proliferation to happen. Indeed, Pl-s alone
      supported cell growth in constitutively activated cell lines (U-937, HeLa, HaCaT,
      and V-79) regardless of the co-presence of v-PL. Plasma- and plasma-derived serum
      were equally able to sustain cell proliferation although, for cells cultured in
      adhesion, the Pl-s was more efficient than the plasma from which it was derived.
      In conclusion, the cells expanded in the presence of the new additives maintained
      their differentiation potential and did not show alterations in their karyotype.

PMID- 29209607
TI  - A Perspective on Extracellular Vesicles Proteomics.
AB  - Increasing attention has been given to secreted extracellular vesicles (EVs) in
      the past decades, especially in the portrayal of their molecular cargo and role
      as messengers in both homeostasis and pathophysiological conditions. This review
      presents the state-of-the-art proteomic technologies to identify and quantify EVs
      proteins along with their PTMs, interacting partners and structural details. The
      rapid growth of mass spectrometry-based analytical strategies for protein
      sequencing, PTMs and structural characterization has improved the level of
      molecular details that can be achieved from limited amount of EVs isolated from
      different biological sources. Here we will provide a perspective view on the
      achievements and challenges on EVs proteome characterization using mass
      spectrometry. A detailed bioinformatics approach will help us to picture the
      molecular fingerprint of EVs and understand better their pathophysiological
      function.

PMID- 29209610
TI  - Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein
      Networks during Hazara Virus Infection.
AB  - Normal epithelial and endothelial renewal and healing after bacterial and viral
      challenges are essential for homeostasis along the intestine and the blood and
      lymphatic vessels. We thus investigated whether and how virus affects migration
      of human epithelial cells and specifically how the nucleocapsid protein (N)
      modulates the cellular proteome and interactome using human Caco-2 cells in a
      wound-healing assay with Hazara virus as a model. Here, Hazara virus blocked cell
      migration in a dose- and time-dependent manner, disrupted the actin cytoskeleton
      and specifically reduced the expression of the IQ-motif-containing GTPase
      activating protein 1 (IQGAP1) and water channel aquaporin 6 (AQP6) that regulate
      cytoskeletal organization, water homeostasis and vesicle communication. Moreover,
      in the Caco-2 cell proteome, we identified several distinct groups of molecules
      associating with N upon Hazara virus infection, being involved in the ensemble of
      important cellular processes, e.g., chaperone activity, metabolism, cellular
      defense against infections, cell morphology, and migration. These events do not
      only facilitate the virus life cycle, but they are also crucial for membrane and
      cytoskeleton dynamics, cellular self-renewal and wound healing, being so
      essential for body integrity and homeostasis.

PMID- 29209611
TI  - Histological Grading of Hepatocellular Carcinoma-A Systematic Review of
      Literature.
AB  - Background: Histological grading typically reflects the biological behavior of
      solid tumors, thus providing valuable prognostic information. This is also
      expected in hepatocellular carcinoma (HCC), although limited access to biopsy
      samples and a lack of standardization might hinder its full predictive value in
      this cancer. Objectives: In order to better understand the current practices of
      histological grading in HCC, we examined the latest publications addressing its
      impact on the outcome of patients following surgical treatment. Methods: We
      searched the PubMed (MEDLINE) database under the headings "hepatocellular
      carcinoma," "grade OR grading," and "prognosis." Qualitative and quantitative
      assessment of publications was performed according to the reference they used to
      grade their tumors (e.g., Edmondson-Steiner, World Health Organization). Results:
      We reviewed a total of 216 articles: 114 enclosed adequate information and were
      included herein. Among these, we found divergences and inaccuracies in the
      histological grade assessment of this cancer, which might have led to a non
      standardized grade distribution, with further impact on data analysis.
      Nevertheless, in most of them, poor tumor differentiation correlated with worse
      prognosis, expressed by lower overall and/or disease-free survival. Conclusion:
      While histological grading of HCC has an important prognostic role, there is an
      unsatisfactory heterogeneity on the microscopic assessment of this tumor, urging
      for a movement toward standardization.

PMID- 29209612
TI  - Anxiety and Depression in the Portuguese Older Adults: Prevalence and Associated
      Factors.
AB  - Anxiety and depression in the elderly individuals have been studied around the
      world, and some authors consider them among the most serious problems faced by
      modern societies. With recent economic crisis-very important in Southern European
      countries-isolation, loneliness, and exclusion of the active society, mental
      problems are probably raising and associated with distinct factors. In this cross
      sectional analysis, nested in a longitudinal population-based cohort study, we
      analyze anxiety and depression prevalence, and their related factors, in a
      representative cohort of Portuguese seniors. We used data retrieved from second
      wave of follow-up of EpiDoC Cohort-EpiDoC 2 study, which is composed by 10,661
      adults, representative of adult Portuguese population. This study included all
      >=65 years old EpiDoC 2 study participants, who responded to Hospital Anxiety and
      Depression Scale (HADS), n = 1,680. Sociodemographic, lifestyles, self-reported
      non-communicable diseases, health-related quality of life (EQ-5D-3D), physical
      function (HAQ), and health resources consumption data were collected. Anxiety and
      depression were assessed with HADS. Anxiety and depression prevalence were
      estimated. Multivariable logistic regression was used to assess anxiety and
      depression score determinants. The estimated prevalence of anxiety among
      Portuguese elderly is 9.6% and depression is 11.8%. Seniors with anxiety and
      seniors with depression have a higher probability to self-report higher levels of
      physical disability (OR = 3.10; 96% CI 2.12-4.52; OR = 3.08, 95% CI 2.29-4.14,
      respectively) and lower levels of quality of life (OR = 0.03, 95% CI 0.01-0.09;
      OR = 0.03, 95% CI 0.01-0.06, respectively). Female gender (OR = 2.77, 95% CI 1.53
      5.00), low educational level (OR = 2.30, 95% CI 1.22-4.36), allergic (OR = 2.02,
      95% CI 1.14-3.55), and rheumatic disease (OR = 2.92, 95% CI 1.74-4.90) were
      significantly and independently associated with the presence of anxiety symptoms.
      Physical inactivity (OR = 1.64, 95% CI 1.11-2.42) and low educational level (OR =
      2.40, 95% CI 1.41-4.09) were significantly and independently associated with
      depression symptoms. Subjects that reported to drink alcohol daily or
      occasionally were negatively associated with depression symptoms. Anxiety and
      depression are frequent among Portuguese elderly. These prevalence rates suggest
      that preventing mental illness in senior population is a crucial need. A well
      designed prevention strategy might have an effective action in raising the well
      being of elderly.

PMID- 29209613
TI  - Evaluation of Phenolic Phytochemical Enriched Commercial Plant Extracts on the In
      Vitro Inhibition of alpha-Glucosidase.
AB  - Green tea (GT), cranberry (CR), and tart cherry extracts were evaluated for their
      ability to inhibit yeast alpha-glucosidase, relevant to glucose uptake. The total
      phenolic content (TPC), antioxidant activity, and in vitro inhibitory activity of
      yeast alpha-glucosidase were examined for the extracts in the present study. GT
      had higher TPC and antioxidant activity, but CR demonstrated a greater alpha
      glucosidase inhibitory activity, on phenolic basis. CR was fractionated using LH
      20 column chromatography into two fractions: 30% methanol (CME) and 70% acetone
      (CAE). TPC, antioxidant activity, and yeast alpha-glucosidase inhibitory activity
      were determined for the fractions. CAE had a greater TPC and antioxidant activity
      than CME, but the two fractions had a synergistic effect when inhibiting yeast
      alpha-glucosidase. Our findings suggest that CR has the greatest potential to
      possibly manage post-prandial blood glucose levels via the inhibition of alpha
      glucosidase, and that the effect is through synergistic activity of the extract's
      phenolic compounds.

PMID- 29209614
TI  - Laryngeal Cryptococcosis Associated With Inhaled Corticosteroid Use: Case Reports
      and Literature Review.
AB  - Laryngeal cryptococcosis is a rare clinical entity. There have been a limited
      number of case reports in the literature with no consensus regarding optimal
      management. This review contributes two additional case reports of
      immunocompetent patients with cryptococcal infection of the larynx in whom
      exposure to high doses of inhaled corticosteroids is proposed as a significant
      risk factor. Twenty cases were identified from review of the literature. All
      patients presented with hoarseness and a spectrum of microlaryngoscopic features,
      often mimicking laryngeal malignancy. The majority of cases were treated with
      systemic antifungal therapy, three cases had surgical excision alone, and another
      three had a combination of medical and surgical management. Risk factor
      modification, in the form of a reduction in inhaled corticosteroid was employed
      in the two new cases, and in some previously published cases. Risk factor
      modification, such as reduction of inhaled corticosteroid dose, in addition to
      oral antifungal agents can be effective in managing cryptococcal laryngitis.

PMID- 29209615
TI  - Simultaneous Hepatic and Mesenteric Hydatid Disease-A Case Report.
AB  - Introduction: Hydatid cysts most commonly present in the liver and the lungs;
      however, they can appear more rarely in other locations, such as the mesentery,
      with a rather unclear mechanism of manifestation. Herein, we present a case of
      simultaneous presence of hydatid cysts in the liver and the mesentery of a young
      man. Case report: A 39-year-old man was referred to our Department for further
      investigation of intermittent abdominal pain, especially in the right upper
      quadrant, and abdominal distension. Abdominal CT imaging revealed three calcified
      lesions, one in the liver, a similar adjacent to an ileal loop and one close to
      the urinary bladder, while antibody control was positive for echinococcal
      infection. The lesions were excised and the patient was discharged on the seventh
      post-operative day in good general condition. Post-operative control after 6
      months did not show any signs of recurrence. Conclusion: Simultaneous presence of
      hydatid cysts in two organs occurs in 5-13% of cases. Presence in the mesentery
      is extremely rare, although, should be included in the classic differential
      diagnosis, especially in endemic areas.

PMID- 29209616
TI  - Extracellular Vesicles as Protagonists of Diabetic Cardiovascular Pathology.
AB  - Extracellular vesicles (EVs) represent an emerging mechanism of cell-cell
      communication in the cardiovascular system. Recent data suggest that EVs are
      produced and taken up by multiple cardiovascular cell types, influencing target
      cells through signaling or transfer of cargo (including proteins, lipids,
      messenger RNA, and non-coding RNA). The concentration and contents of circulating
      EVs are altered in several diseases and represent explicit signatures of cellular
      activation, making them of particular interest as circulating biomarkers. EVs
      also actively contribute to the progression of various cardiovascular diseases,
      including diabetes-related vascular disease. Understanding the relationships
      between circulating EVs, diabetes, and cardiovascular disease is of importance as
      diabetic patients are at elevated risk for developing several debilitating
      cardiovascular pathologies, including diabetic cardiomyopathy (DCM), a disease
      that remains an enigma at the molecular level. Enhancing and exploiting our
      understanding of EV biology could facilitate the development of effective non
      invasive diagnostics, prognostics, and therapeutics. This review will focus on EV
      biology in diabetic cardiovascular diseases, including atherosclerosis and DCM.
      We will review EV biogenesis and functional properties, as well as provide
      insight into their emerging role in cell-cell communication. Finally, we will
      address the utility of EVs as clinical biomarkers and outline their impact as a
      biomedical tool in the development of therapeutics.

PMID- 29209617
TI  - MiRroring the Multiple Potentials of MicroRNAs in Acute Myocardial Infarction.
AB  - At present, cardiovascular diseases are depicted to be the leading cause of death
      worldwide according to the World Health Organization. In the future, projections
      predict that ischemic heart disease will persist in the top main causes of
      illness. Within this alarming context, some tiny master regulators of gene
      expression programs, namely, microRNAs (miRNAs) carry three promising potentials.
      In fact, miRNAs can prove to be useful not only in terms of biomarkers allowing
      heart injury detection but also in terms of therapeutics to overcome limitations
      of past strategies and treat the lesions. In a more creative approach, they can
      even be used in the area of human engineered cardiac tissues as maturation tools
      for cardiomyocytes (CMs) derived from pluripotent stem cell. Very promising not
      only for patient-specific cell-based therapies but also to develop biomimetic
      microsystems for disease modeling and drug screening, these cells greatly
      contribute to personalized medicine. To get into the heart of the matter, the
      focus of this review lies primarily on miRNAs as acute myocardial infarction
      (AMI) biomarkers. Only large cohort studies comprising over 100 individuals to
      reach a potent statistical value were considered. Certain miRNAs appeared to
      possibly complement protein-based biomarkers and classical risk factors. Some
      were even described to bear potential in the discrimination of similar
      symptomatic pathologies. However, differences between pre-analytical and
      analytical approaches substantially influenced miRNA data. Further supported by
      meta-analysis studies, this problem had to be addressed. A detailed critical
      analysis of each step to define miRNAs biomarker potential is provided to inspire
      a future improved universal strategy. Interestingly, a recurrent set of
      cardiomyocyte-enriched miRNAs was found, namely, miR-1; miR-133; miR-208a/b; and
      miR-499a. Each member of this myomiRs group displayed promising roles either
      individually or in combination as AMI diagnostic or prognostic biomarkers.
      Furthermore, a precise combo was shown to be powerful enough to
      transdifferentiate human fibroblasts into CMs opening doors in the therapeutics.
      Following these discoveries, they also emerged as optional tools to transfect in
      order to mature CMs derived from pluripotent stem cells. Ultimately, the multiple
      potentials carried by the myomiRs miR-1; miR-133; miR-208a/b; and miR-499a still
      remain to be fully unveiled.

PMID- 29209620
TI  - Editorial: Modeling Disease Spread and Control.

PMID- 29209619
TI  - Circulating MicroRNAs As Potential Biomarkers for Veterinary Infectious Diseases.
AB  - MicroRNAs (miRNAs) are a kind of small non-coding RNA molecules that could
      regulate multiple biological pathways at posttranscriptional level. Over 2,000
      miRNAs have so far been discovered in humans, and many of them are found to be
      linked to various kinds of diseases. Thus, miRNAs are being considered as
      clinical diagnostic and therapeutic targets. With the discovery of high stability
      of circulating miRNAs in various kinds of mammalian body fluids, the potential of
      circulating miRNAs as diagnostic/prognostic biomarkers of infectious diseases
      aroused great interest among researchers. As far as human diseases are concerned,
      some biomarkers based on circulating miRNAs have been progressed to clinical
      application. In veterinary fields, however, this concept is only beginning to
      come into view. In this review, we summarize an update of preclinical studies on
      using circulating miRNAs as diagnostic biomarkers to combat infectious diseases
      that affect domestic animals.

PMID- 29209618
TI  - Platelet-Derived Microvesicles in Cardiovascular Diseases.
AB  - Microvesicles (MVs) circulating in the blood are small vesicles (100-1,000 nm in
      diameter) derived from membrane blebs of cells such as activated platelets,
      endothelial cells, and leukocytes. A growing body of evidence now supports the
      concept that platelet-derived microvesicles (PMVs), the most abundant MVs in the
      circulation, are important regulators of hemostasis, inflammation, and
      angiogenesis. Compared with healthy individuals, a large increase of circulating
      PMVs has been observed, particularly in patients with cardiovascular diseases. As
      observed in MVs from other parent cells, PMVs exert their biological effects in
      multiple ways, such as triggering various intercellular signaling cascades and by
      participating in transcellular communication by the transfer of their "cargo" of
      cytoplasmic components and surface receptors to other cell types. This review
      describes our current understanding of the potential role of PMVs in mediating
      hemostasis, inflammation, and angiogenesis and their consequences on the
      pathogenesis of cardiovascular diseases, such as atherosclerosis, myocardial
      infarction, and venous thrombosis. Furthermore, new developments of the
      therapeutic potential of PMVs for the treatment of cardiovascular diseases will
      be discussed.

PMID- 29209621
TI  - Influence of environmental conditions and pollution on the incidence of
      Streptococcus pneumoniae infections.
AB  - Fossil fuel derived pollutants (SO2, NO), dry air and cold increase the incidence
      of S. pneumoniae infections http://ow.ly/RnLW30gogb1.

PMID- 29209623
TI  - MYC Gene Rearrangements Are Closely Associated with Poor Survival of Diffuse
      Large B Cell Lymphoma with Hepatitis B Virus Infection.
AB  - The aim of this study was to identify clinical adverse prognostic factors
      affecting overall survival (OS) of diffuse large B cell (DLBCL) patients with
      hepatitis B virus (HBV) infection. In this study, 30 DLBCL patients with HBV
      infection and 51 DLBCL patients with HBV-free were reviewed retrospectively. As
      of July 2016, the median follow-up period was 26.4 months (3.0~65.0 months). The
      median OS of patients in HBV infection group was 38.6 months, while that of
      patients in HBV-free group was not reached (P = 0.042); the median progression
      free survival (PFS) of patients in HBV infection group was worse than that in HBV
      free group, 18.5 months and 38.5 months (P = 0.118), respectively. The rate of
      MYC and BCL2 gene rearrangements in HBV infection group was significantly higher
      than that in HBV-free group, 20.0% versus 3.9% (P = 0.019) and 23.3% versus 5.9%
      (P = 0.021), respectively. Multivariable analysis indicated that IPI (P = 0.002),
      chemotherapy regimens (P = 0.017), and MYC gene rearrangements (P = 0.004) were
      independent adverse prognostic factors for all DLBCL patients in this study.
      Results demonstrated that the poor survival of DLBCL patients with HBV infection
      was closely involved in chemotherapy regimens, IPI, and MYC gene rearrangements.

PMID- 29209622
TI  - Exploration of the Association between Nurses' Moral Distress and Secondary
      Traumatic Stress Syndrome: Implications for Patient Safety in Mental Health
      Services.
AB  - Work-related moral distress (MD) and secondary traumatic stress syndrome (STSS)
      may be associated with compromised health status among health professionals,
      reduced productivity, and inadequate safety of care. We explored the association
      of MD with the severity of STSS symptoms, along with the mediating role of mental
      distress symptoms. Associations with emotional exhaustion and professional
      satisfaction were also assessed. This cross-sectional survey conducted in 206
      mental health nurses (MHNs) was employed across public sector community and
      hospital settings in Cyprus. The analysis revealed that MD (measured by the
      modified Moral Distress Scale) was positively associated with both STSS (measured
      by the Secondary Traumatic Stress Scale) and mental distress symptoms (assessed
      by the General Health Questionnaire-28). The association of MD with STSS symptoms
      was partially mediated by mental distress symptoms. This association remained
      largely unchanged after adjusting for gender, age, education, rank, and intention
      to quit the job. Our findings provide preliminary evidence on the association
      between MD and STSS symptomatology in MHNs. Situations that may lead health
      professionals to be in moral distress seem to be mainly related to the work
      environment; thus interventions related to organizational empowerment of MHNs
      need to be developed.

PMID- 29209624
TI  - In Vitro Antibacterial Activity of Pomegranate Juice and Peel Extracts on
      Cariogenic Bacteria.
AB  - Aim: To evaluate the antimicrobial activity of hydroalcoholic extracts of
      pomegranate (Punica granatum L.) peel and juice, against the microorganisms
      considered the main etiologic agents of dental caries. Methods: The values of the
      minimum inhibitory concentration (MIC) and the minimum bactericidal concentration
      (MBC) were determined against Streptococcus mutans Clarke ATCC(r) 25175TM strain
      and Rothia dentocariosa clinical isolate. Results: Peel extracts inhibit
      effectively the growth and survival of S. mutans ATCC 25175 strain and R.
      dentocariosa clinical isolate with MIC and MBC values of 10 MUg/MUl and 15
      MUg/MUl, respectively. Furthermore, the pomegranate juice extract showed high
      inhibitory activity against S. mutans ATCC 25175 strain with a MIC value of 25
      MUg/MUl and a MBC value of 40 MUg/MUl, whereas, against R. dentocariosa, it has
      displayed a moderate inhibitory activity, with MIC and MBC values of 20 MUg/MUl
      and 140 MUg/MUl, respectively. Conclusions: In vitro microbiological tests
      demonstrate that the hydroalcoholic extracts of pomegranate juice and peel are
      able to contrast the main cariogenic bacteria involved in tooth decay. Although
      being preliminary data, our results suggest that pomegranate polyphenolic
      compounds could represent a good adjuvant for the prevention and treatment of
      dental caries.

PMID- 29209625
TI  - Prediction and Validation of Hub Genes Associated with Colorectal Cancer by
      Integrating PPI Network and Gene Expression Data.
AB  - Although hundreds of colorectal cancer- (CRC-) related genes have been screened,
      the significant hub genes still need to be further identified. The aim of this
      study was to identify the hub genes based on protein-protein interaction network
      and uncover their clinical value. Firstly, 645 CRC patients' data from the Tumor
      Cancer Genome Atlas were downloaded and analyzed to screen the differential
      expression genes (DEGs). And then, the Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment analysis was performed, and PPI network of the DEGs was
      constructed by Cytoscape software. Finally, four hub genes (CXCL3, ELF5, TIMP1,
      and PHLPP2) were obtained from four subnets and further validated in our clinical
      setting and TCGA dataset. The results showed that mRNA expression of CXCL3, ELF5,
      and TIMP1 was increased in CRC tissues, whereas PHLPP2 mRNA expression was
      decreased. More importantly, high expression of CXCL3, ELF5, and TIMP1 was
      significantly associated with lymphatic invasion, distance metastasis, and
      advanced tumor stage. In addition, a shorter overall survival was observed in
      patients with increased CXCL3, TIMP1, and ELF5 expression and decreased PHLPP2
      expression. In conclusion, the four hub genes screened by our strategy could
      serve as novel biomarkers for prognosis prediction of CRC patients.

PMID- 29209626
TI  - Neovascular Prostate-Specific Membrane Antigen Expression Is Associated with
      Improved Overall Survival under Palliative Chemotherapy in Patients with
      Pancreatic Ductal Adenocarcinoma.
AB  - Aims: Expression of PSMA (prostate-specific membrane antigen) has been
      demonstrated in various cancers, including pancreatic ductal adenocarcinoma
      (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not
      been systematically analyzed. Methods and Results: We analyzed PSMA expression in
      81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed
      by software-based image analysis and showed a mean MVD of 63.7 microvessels/0.785
      mm2. PSMA was practically absent in tumor tissue (5.3%) and PDAC cell lines (0/7)
      but could be detected in tumor-associated neovasculature in 53.2% of cases. There
      was no association between neovascular PSMA expression and clinicopathological
      tumor characteristics. Samples with PSMA+ neovasculature showed increased MVD;
      however, this result was not statistically significant (p > 0.05). Presence of
      PSMA+ neovessels correlated with overall survival under palliative chemotherapy
      (894 versus 400 days; HR 0.42; 95% CI: 0.12 to 0.87; p < 0.05). Conclusion: PSMA
      expression in tumor-associated neovasculature is a common feature and associated
      with improved overall survival under palliative chemotherapy in PDAC. Our results
      point towards a possible association between PSMA expression and response to
      therapy which might be based on enhanced intratumoral bioavailability of systemic
      chemotherapy.

PMID- 29209627
TI  - Thermosensitive Chitosan Hydrogels Containing Polymeric Microspheres for Vaginal
      Drug Delivery.
AB  - Thermosensitive hydrogels have increasingly received considerable attention for
      local drug delivery based on many advantages. However, burst release of drugs is
      becoming a critical challenge when the hydrogels are employed. Microspheres- (MS
      ) loaded thermosensitive hydrogels were thus fabricated to address this
      limitation. Employing an orthogonal design, the spray-dried operations of
      tenofovir (TFV)/Bletilla striata polysaccharide (BSP)/chitosan (CTS) MS were
      optimized according to the drug loading (DL). The physicochemical properties of
      the optimal MS (MS F) were characterized. Depending on the gelation temperature
      and gelating time, the optimal CTS-sodium alginate- (SA-) alpha,beta
      glycerophosphate (GP) (CTS-SA-GP) hydrogel was obtained. Observed by scanning
      electron microscope (SEM), TFV/BSP/CTS MS were successfully encapsulated in CTS
      SA-GP. In vitro releasing demonstrated that MS F-CTS-SA-GP retained desirable in
      vitro sustained-release characteristics as a vaginal delivery system. Bioadhesion
      measurement showed that MS-CTS-SA-GP exhibited the highest mucoadhesive strength.
      Collectively, MS-CTS-SA-GP holds great promise for topical applications as a
      sustained-release vaginal drug delivery system.

PMID- 29209628
TI  - Inhibitors of Histone Deacetylases Are Weak Activators of the FMR1 Gene in
      Fragile X Syndrome Cell Lines.
AB  - Fragile X syndrome is the most common cause of inherited intellectual disability
      in humans. It is a result of CGG repeat expansion in the 5' untranslated region
      (5' UTR) of the FMR1 gene. This gene encodes the FMRP protein that is involved in
      neuronal development. Repeat expansion leads to heterochromatinization of the
      promoter, gene silencing, and the subsequent absence of FMRP. To date, there is
      no specific therapy for the syndrome. All treatments in clinic practice provide
      symptomatic therapy. The development of drug therapy for Fragile X syndrome
      treatment is connected with the search for inhibitors of enzymes that are
      responsible for heterochromatinization. Here, we report a weak transcriptional
      activity of the FMR1 gene and the absence of FMRP protein after Fragile X
      syndrome cell lines treatment with two FDA approved inhibitors of histone
      deacetylases, romidepsin and vorinostat. We demonstrate that romidepsin, an
      inhibitor of class I histone deacetylases, does not activate FMR1 expression in
      patient cell cultures, whereas vorinostat, an inhibitor of classes I and II
      histone deacetylases, activates a low level of FMR1 expression in some patient
      cell lines.

PMID- 29209629
TI  - Corrigendum to "Effects of Chronic Exposure to Sodium Arsenite on Expressions of
      VEGF and VEGFR2 Proteins in the Epididymis of Rats".
AB  - [This corrects the article DOI: 10.1155/2017/2597256.].

PMID- 29209630
TI  - Barriers to Physical Activity in Low Back Pain Patients following Rehabilitation:
      A Secondary Analysis of a Randomized Controlled Trial.
AB  - Background: Promoting health-enhancing physical activity following rehabilitation
      is a well-known challenge. This study analysed the barriers to leisure time
      activity among low back pain patients. Methods: A subset of 192 low back pain
      patients who participated in a randomized controlled trial promoting physical
      activity was analysed. Physical activity, barriers, and sociodemographic and
      indication-related variables were assessed by a questionnaire. Differences in
      barriers between active and inactive participants were tested by Pearson's chi
      squared test. A logistic regression model was fitted to identify influencing
      factors on physical activity at six months following rehabilitation. Results:
      Inactive and active participants differed significantly in nine of the 19
      barriers assessed. The adjusted regression model showed associations of level of
      education (OR = 5.366 [1.563; 18.425]; p value = 0.008) and fear of pain (OR =
      0.612 [0.421; 0.889]; p value = 0.010) with physical activity. The barriers
      included in the model failed to show any statistically significant association
      after adjustment for sociodemographic factors. Conclusions: Low back pain
      patients especially with a low level of education and fear of pain seem to need
      tailored support in overcoming barriers to physical activity. This study is
      registered at German Clinical Trials Register (DRKS00004878).

PMID- 29209631
TI  - Maxillary Sinus Floor Augmentation Using an Equine-Derived Graft Material:
      Preliminary Results in 17 Patients.
AB  - Objective: Sinus floor elevation with lateral approach is probably the most
      frequently performed reconstructive procedure to rehabilitate posterior maxilla
      when a bone deficiency is present. Different graft materials have been proposed
      and tested, often with high clinical performances and predictable results.
      Histological analysis is required when evaluating new materials. We investigated
      human biopsies retrieved after sinus floor elevation procedure by
      histomorphometric evaluation to test the performance of an equine-derived bone
      grafting material. Study Design: Seventeen consecutive patients were enrolled and
      sinus lift surgeries were performed using an equine bone graft. Six months after
      surgery, at implant placement, bone samples were collected. Histomorphometry
      analysis was carried out on decalcified samples. Results: All surgeries were
      uneventful and no additional grafting was required prior to implant insertion.
      Forty percent of new bone formation was detected, which represented the most
      abundant tissue retrieved, followed by the residual graft material (33%) and
      fibrous tissue (27%). A significant reduction in particles size demonstrates a
      remodeling activity of the graft material. Conclusion: Within the limitations of
      this study, this equine-derived bone graft proved to be an effective material to
      induce new bone formation in the sinus floor elevation procedure.

PMID- 29209632
TI  - Silymarin Ameliorates Diabetes-Induced Proangiogenic Response in Brain
      Endothelial Cells through a GSK-3beta Inhibition-Induced Reduction of VEGF
      Release.
AB  - Diabetes mellitus (DM) is a major risk factor for cardiovascular disease.
      Additionally, it was found to induce a dysfunctional angiogenic response in the
      brain that was attributed to oxidative stress. Milk thistle seed extract
      (silymarin) has potent antioxidant properties, though its potential use in
      ameliorating diabetes-induced aberrant brain angiogenesis is unknown. Glycogen
      synthase kinase-3beta is a regulator of angiogenesis that is upregulated by
      diabetes. Its involvement in diabetes-induced angiogenesis is unknown. To
      evaluate the potential of silymarin to ameliorate diabetes-induced aberrant
      angiogenesis, human brain endothelial cells (HBEC-5i) were treated with 50 MUg/mL
      advanced glycation end (AGE) products in the presence or absence of silymarin
      (50, 100 MUM). The angiogenic potential of HBEC-5i was evaluated in terms of
      migration and in vitro tube formation capacities. The involvement of GSK-3beta
      was also evaluated. AGE significantly increased the migration and tube formation
      rates of HBEC-5i by about onefold (p = 0.0001). Silymarin reduced AGE-induced
      migration in a dose-dependent manner where 50 MUM reduced migration by about 50%,
      whereas the 100 MUM completely inhibited AGE-induced migration. Similarly,
      silymarin 50 MUg/mL blunted AGE-induced tube formation (p = 0.001). This effect
      was mediated through a GSK-3beta-dependent inhibition of VEGF release. In
      conclusion, silymarin inhibits AGE-induced aberrant angiogenesis in a GSK-3beta
      mediated inhibition of VEGF release.

PMID- 29209634
TI  - The Vilkki Procedure as an emergency treatment in an apocalyptical hand injury -
      a case report and first description.
AB  - We describe a young man who suffered a severe mutilating injury of the hand and
      forearm while working as a cheesemaker. He underwent a complex reconstruction of
      his right adominant hand including a heterotopic thumb replantation into the
      distal radius and combined with an emergency flow-through anterolateral thigh
      flap.

PMID- 29209633
TI  - Protein Intake, Especially Vegetable Protein Intake, Is Associated with Higher
      Skeletal Muscle Mass in Elderly Patients with Type 2 Diabetes.
AB  - Background/Aims: Protein intake is important for maintaining muscle mass in
      general population. However, it remains to be elucidated the association between
      dietary protein intake and skeletal muscle mass in elderly patients with type 2
      diabetes. Methods: In this cross-sectional study of 168 elderly patients with
      type 2 diabetes, we investigated the relationship between skeletal muscle index
      (SMI) and protein intake. Bioimpedance analysis was used for measurement for
      skeletal muscle mass (kg) and SMI (%), which was defined as skeletal muscle mass
      (kg)/total body weight (kg) * 100. Habitual food and nutrient intake were
      estimated by a questionnaire. Results: Protein intake was independently
      correlated with SMI after adjusting for age, hemoglobin A1c, C-peptide index,
      exercise, smoking, insulin treatment, total energy intake, and C-reactive protein
      (standardized regression coefficient = 0.664, P < 0.001 in men and standardized
      regression coefficient = 0.516, P = 0.005 in women). Additionally, the animal
      protein to vegetable protein ratio was negatively correlated with SMI after
      adjusting for covariates in men (standardized regression coefficient = -0.339, P
      = 0.005). Conclusions: We found that total protein intake, especially vegetable
      protein intake, was positively associated with skeletal muscle mass in elderly
      patients with type 2 diabetes.

PMID- 29209635
TI  - Serum neurofilament light chain in relapsing-remitting MS: Unchaining disease
      activity prediction?

PMID- 29209637
TI  - A role for p53 in telomere protection.
AB  - Telomeres cap the ends of chromosomes and are crucial for genome stability. The
      p53 protein (TP53) is a vital tumor suppressor, activating the transcription of
      numerous genes in response to cell stress. We reported that direct binding of p53
      at human subtelomeres corresponds with local transcription activation and
      enhanced telomere stability in the presence of DNA damage.

PMID- 29209638
TI  - Sensitizing HR-proficient cancers to PARP inhibitors.

PMID- 29209636
TI  - Neurofilament light chain predicts disease activity in relapsing-remitting MS.
AB  - Objective: To investigate whether serum neurofilament light chain (NF-L) and
      chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS
      (RRMS). Methods: A cohort of 85 patients with RRMS were followed for 2 years (6
      months without disease-modifying treatment and 18 months with interferon-beta 1a
      [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6
      months thereafter. MRI was performed at baseline and monthly for 9 months and
      then at months 12 and 24. Serum samples were collected at baseline and months 3,
      6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array
      assay and CHI3L1 by ELISA and estimated the association with clinical and MRI
      disease activity using mixed-effects models. Results: NF-L levels were
      significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3
      pg/mL, interquartile range [IQR] 25.9-52.4) and new T2 lesions (37.3 pg/mL, IQR
      25.1-48.5) compared with those without (28.0 pg/mL, IQR 21.9-36.4, beta = 1.258,
      p < 0.001 and 27.7 pg/mL, IQR 21.8-35.1, beta = 1.251, p < 0.001, respectively).
      NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions
      up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of
      biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p
      < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease
      activity or interferon-beta 1a treatment. Conclusion: Serum NF-L could be a
      promising biomarker for subclinical MRI activity and treatment response in RRMS.
      In clinically stable patients, serum NF-L may offer an alternative to MRI
      monitoring for subclinical disease activity. ClinicalTrialsgov identifier:
      NCT00360906.

PMID- 29209639
TI  - Enhancer remodeling regulates epigenetic adaptation and resistance to MEK1/2
      inhibition in triple-negative breast cancer.
AB  - Kinase inhibitors targeting the mitogen/extracellular signal-regulated kinase
      kinase (MEK)- extracellular signal related kinase (ERK) signaling pathway have
      limited durability in inhibiting growth of triple-negative breast cancer. We
      defined genome wide enhancer remodeling following MEK inhibition capable of
      driving adaptive gene transcription. Targeting positive elongation factor (P
      TEFb) transcriptional regulatory complex members can block enhancer remodeling
      making the response to MEK-ERK inhibition durable.

PMID- 29209640
TI  - Some assembly required: Redefining the mitotic checkpoint.
AB  - The spindle assembly checkpoint (also known as the spindle or mitotic checkpoint)
      is a surveillance system that ensures fidelity of chromosome segregation. Here we
      suggest, in light of historical and more recent evidence, that this signaling
      system monitors kinetochore attachment and spindle assembly by two distinct, but
      functionally overlapping, pathways.

PMID- 29209642
TI  - PARK2 loss promotes cancer progression via redox-mediated inactivation of PTEN.
AB  - Cancer and Parkinson disease (PD) derive from distinct alterations in cellular
      processes, yet there are pathogenic mutations that are unequivocally linked to
      both diseases. Here we expand on our recent findings that loss of parkin RBR E3
      ubiquitin protein ligase (PRKN, best known as PARK2)-which is genetically linked
      to PD-promotes cancer progression via redox-mediated inactivation of phosphatase
      and tensin homolog (PTEN) by S-nitrosylation.

PMID- 29209641
TI  - The folate cycle is a new metabolic weakness of cancer.
AB  - Cancer cells harness nutrients to support its rapid proliferation through
      metabolic reprogramming. Our report identified folate cycle as a metabolic target
      in hepatocellular carcinoma. Folate cycle stagnation via inhibition of its
      mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase 1-like
      (MTHFD1L) greatly induced oxidative stress improving HCC cells' response to
      sorafenib.

PMID- 29209644
TI  - New role of endoplasmic reticulum chaperones in regulating metaplasia during
      tumorigenesis.
AB  - Metaplasia is emerging as a key process in tumorigenesis. We discovered that 2
      essential endoplasmic reticulum (ER) chaperones, 78-kilodalton glucose-regulated
      protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) have a role
      in metaplasia. Grp78 haploinsufficiency in the mouse pancreas impairs acinar-to
      ductal metaplasia, whereas in the uterus, Grp94 loss induces squamous cell
      metaplasia; both resulting in tumor suppression.

PMID- 29209643
TI  - NRAS-driven melanoma: A RAF can hide another.
AB  - Using mouse genetics, we recently showed that BRAF has a critical role in
      initiation of NRAS-driven melanoma that cannot be compensated by CRAF. In
      contrast, RAF proteins display compensatory functions in fully established tumors
      and ARAF can sustain proliferation in the absence of BRAF and CRAF, highlighting
      an addiction to RAF signaling in NRAS-driven melanoma.

PMID- 29209645
TI  - Molecular pathways driven by ETO2-GLIS2 in aggressive pediatric leukemia.
AB  - The ETO2-GLIS2 fusion oncoprotein is associated with poor prognosis pediatric
      acute megakaryoblastic leukemia. Recently, we observed that ETO2-GLIS2 controls
      enhancers activity at genes regulating haematopoietic progenitor self-renewal and
      differentiation toward the megakaryocytic lineage. We also showed that targeting
      ETO2-GLIS2 complex stability inhibits these properties and may represent a novel
      therapeutic strategy.

PMID- 29209647
TI  - Targeting RAS - will GPR31 deliver us a new path forward?
AB  - Effective anti-rat sarcoma viral oncogene (RAS) therapies have remained the holy
      grail of cancer treatment. Mutant Kirsten rat sarcoma viral oncogene homolog
      (KRAS) sustains tumorigenesis when linked to the plasma membrane (PM). The G
      protein-coupled receptor 31 (GPR31) is now identified to mediate KRAS membrane
      association and is crucial for proliferation, survival and macropinocytosis of
      KRAS-dependent cancer cells, suggesting that GPR31 is a druggable target for anti
      RAS therapy.

PMID- 29209646
TI  - Re-investigating PLK1 inhibitors as antimitotic agents.
AB  - Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the
      development of PLK1 inhibitors for anticancer therapy. We recently determined
      that PLK1 is crucially required for entry into mitosis. Hence, we discuss the
      potential and limitations of PLK1 inhibition strategies to promote mitotic arrest
      and death of cancer cells.

PMID- 29209648
TI  - Linking H1 with chromatin and growth control.
AB  - The retinoblastoma protein (pRb) is considered to be one of the key regulators of
      cell proliferation. Here we describe our recent findings that linker histone H1.2
      is an interaction partner for pRb and impacts upon the genome-wide chromatin
      binding properties of pRb. Consequently, H1.2 influences transcriptional
      repression and cell cycle control.

PMID- 29209649
TI  - Breaking the end: Target the replication stress response at the ALT telomeres for
      cancer therapy.
AB  - We recently reported that depletion of FANCM in ALT cells induces replication
      stress mainly at their telomeres. Additionally, we found that co-depletion of
      FANCM and BLM, or FANCM and BRCA1 induces synthetic lethality in the ALT cells.
      Our new findings could have important implications for cancer prevention and
      treatment.

PMID- 29209650
TI  - KEAP1 has a sweet spot: A new connection between intracellular glycosylation and
      redox stress signaling in cancer cells.
AB  - The KEAP1/NRF2 pathway is a master regulator of the redox stress response and is
      dysregulated in numerous human tumors. We discovered that NRF2 signaling is
      controlled by the site-specific glycosylation of KEAP1, revealing a potentially
      broad link among nutrient sensing, proteostasis and stress resistance in both
      normal and cancer cells.

PMID- 29209651
TI  - PML degradation fosters an immunosuppressive and pro-metastatic tumor
      microenvironment.
AB  - The tumor suppressive functions of promyelocytic leukemia (PML) have been
      attributed mainly to its inhibition of various malignant properties of tumor
      cells. Our recent work identifies a PML ubiquitination and degradation pathway,
      which regulates both cell and non-cell components of the tumor microenvironment,
      thereby potentiating immune evasion and metastasis.

PMID- 29209652
TI  - Sestrin1, a tumor suppressor that can be rescued.
AB  - SESTRIN1 is a tumor suppressor in follicular lymphoma that controls mTORC1
      activity and it is inactivated by chromosomal deletions or epigenetically
      silenced by mutant EZH2Y641X. Pharmacological inhibition of EZH2 promotes
      SESTRIN1 re-expression and it restores its tumor suppressive activity, suggesting
      the possibility to epigenetically control mTORC1 activity.

PMID- 29209653
TI  - Unveiling the role of VPS34 kinase domain dynamics in regulation of the
      autophagic PI3K complex.
AB  - The class III PI 3-kinase, VPS34 forms distinct complexes essential for cargo
      sorting and membrane trafficking in endocytosis as well as for autophagosome
      nucleation and maturation. We used integrative structural biology approach to
      provide insights into the conformational dynamics of the complex and mechanisms
      that regulate VPS34 activity at the membrane.

PMID- 29209654
TI  - Tumor stiffness extends its grip on the metastatic microenvironment.
AB  - The increased stiffness of a tumor triggers a multitude of responses that aid
      cancer cell dissemination. Stiffness-induced expression of CCN1 mediates
      autocrine signaling in the endothelium to upregulate N-Cadherin levels. This
      permits more stable interactions with cancer cells and increases their ability to
      spread into the circulation.

PMID- 29209655
TI  - The E3 ubiquitin ligase STUB1 regulates autophagy and mitochondrial biogenesis by
      modulating TFEB activity.
AB  - TFEB is a master regulator for transcription of genes involved in autophagy,
      lysosome and mitochondrial biogenesis. Activity of TFEB is inhibited upon its
      phosphorylation. STUB1, a chaperone-dependent E3 ubiquitin ligase, modulates TFEB
      activity by preferentially targeting inactive phosphorylated TFEB for degradation
      by the ubiquitin proteasome pathway. Thus, the ubiquitin-proteasome pathway
      participates in regulating autophagy and lysosomal functions by regulating the
      activity of TFEB.

PMID- 29209656
TI  - Ionic signalling and mitochondrial dynamics.
AB  - In age-related diseases, rise in intracellular reactive oxygen species (ROS)
      causes fragmentation of mitochondrial network. Our recent study demonstrated that
      ROS activation of TRPM2 (transient receptor potential melastatin-2) channels
      triggers lysosomal Zn2+ release that, in turn, triggers mitochondrial
      fragmentation. The findings provide new mechanistic insights that may have
      therapeutic implications.

PMID- 29209657
TI  - Hitting the snooze button: Inducing quiescence with the FLT3 inhibitor
      quizartinib protects hematopoietic progenitors from chemotherapy.
AB  - Myelosuppression is one of the most severe and limiting side effects of
      chemotherapy. Our recent work outlines a strategy to prevent chemotherapy-induced
      myelosuppression by administering a priming dose of the FMS-Like Tyrosine kinase
      3 (FLT3) inhibitor quizartinib. Furthermore, by administering sequential
      quizartinib primed injections of fluorouracil (5-FU), we demonstrated a novel and
      effective strategy to eliminate disease in two mouse models of quizartinib
      resistant acute myeloid leukemia (AML).

PMID- 29209658
TI  - Surgical Pathology Resident Rotation Restructuring at a Tertiary Care Academic
      Center.
AB  - Changes in the field of pathology and resident education necessitate ongoing
      evaluation of residency training. Evolutionary change is particularly important
      for surgical pathology rotations, which form the core of anatomic pathology
      training programs. In the past, we organized this rotation based on subjective
      insight. When faced with the recent need to restructure the rotation, we strove
      for a more evidence-based process. Our approach involved 2 primary sources of
      data. We quantified the number of cases and blocks submitted per case type to
      estimate workload and surveyed residents about the time required to gross
      specimens in all organ systems. A multidisciplinary committee including faculty,
      residents, and staff evaluated the results and used the data to model how various
      changes to the rotation would affect resident workload, turnaround time, and
      other variables. Finally, we identified rotation structures that equally
      distributed work and created a point-based system that capped grossing time for
      residents of different experience. Following implementation, we retrospectively
      compared turnaround time and duty hour violations before and after these changes
      and surveyed residents about their experiences with both systems. We evaluated
      the accuracy of the point-based system by examining grossing times and comparing
      them to the assigned point values. We found overall improvement in the rotation
      following the implementation. As there is essentially no literature on the
      subject of surgical pathology rotation organization, we hope that our experience
      will provide a road map to improve pathology resident education at other
      institutions.

PMID- 29209659
TI  - Imaging paleoslabs in the D" layer beneath Central America and the Caribbean
      using seismic waveform inversion.
AB  - D" (Dee double prime), the lowermost layer of the Earth's mantle, is the thermal
      boundary layer (TBL) of mantle convection immediately above the Earth's liquid
      outer core. As the origin of upwelling of hot material and the destination of
      paleoslabs (downwelling cold slab remnants), D" plays a major role in the Earth's
      evolution. D" beneath Central America and the Caribbean is of particular
      geodynamical interest, because the paleo- and present Pacific plates have been
      subducting beneath the western margin of Pangaea since ~250 million years ago,
      which implies that paleoslabs could have reached the lowermost mantle. We conduct
      waveform inversion using a data set of ~7700 transverse component records to
      infer the detailed three-dimensional S-velocity structure in the lowermost 400 km
      of the mantle in the study region so that we can investigate how cold paleoslabs
      interact with the hot TBL above the core-mantle boundary (CMB). We can obtain
      high-resolution images because the lowermost mantle here is densely sampled by
      seismic waves due to the full deployment of the USArray broadband seismic
      stations during 2004-2015. We find two distinct strong high-velocity anomalies,
      which we interpret as paleoslabs, just above the CMB beneath Central America and
      Venezuela, respectively, surrounded by low-velocity regions. Strong low-velocity
      anomalies concentrated in the lowermost 100 km of the mantle suggest the
      existence of chemically distinct denser material connected to low-velocity
      anomalies in the lower mantle inferred by previous studies, suggesting that plate
      tectonics on the Earth's surface might control the modality of convection in the
      lower mantle.

PMID- 29209660
TI  - Mesocrystalline calcium silicate hydrate: A bioinspired route toward elastic
      concrete materials.
AB  - Calcium silicate hydrate (C-S-H) is the binder in concrete, the most used
      synthetic material in the world. The main weakness of concrete is the lack of
      elasticity and poor flexural strength considerably limiting its potential, making
      reinforcing steel constructions necessary. Although the properties of C-S-H could
      be significantly improved in organic hybrids, the full potential of this approach
      could not be reached because of the random C-S-H nanoplatelet structure. Taking
      inspiration from a sea urchin spine with highly ordered nanoparticles in the
      biomineral mesocrystal, we report a bioinspired route toward a C-S-H mesocrystal
      with highly aligned C-S-H nanoplatelets interspaced with a polymeric binder. A
      material with a bending strength similar to nacre is obtained, outperforming all
      C-S-H-based materials known to date. This strategy could greatly benefit future
      construction processes because fracture toughness and elasticity of brittle
      cementitious materials can be largely enhanced on the nanoscale.

PMID- 29209661
TI  - Origami lattices with free-form surface ornaments.
AB  - Lattice structures are used in the design of metamaterials to achieve unusual
      physical, mechanical, or biological properties. The properties of such
      metamaterials result from the topology of the lattice structures, which are
      usually three-dimensionally (3D) printed. To incorporate advanced functionalities
      into metamaterials, the surface of the lattice structures may need to be
      ornamented with functionality-inducing features, such as nanopatterns or
      electronic devices. Given our limited access to the internal surfaces of lattice
      structures, free-form ornamentation is currently impossible. We present lattice
      structures that are folded from initially flat states and show that they could
      bear arbitrarily complex surface ornaments at different scales. We identify three
      categories of space-filling polyhedra as the basic unit cells of the cellular
      structures and, for each of those, propose a folding pattern. We also demonstrate
      "sequential self-folding" of flat constructs to 3D lattices. Furthermore, we
      folded auxetic mechanical metamaterials from flat sheets and measured the
      deformation-driven change in their negative Poisson's ratio. Finally, we show how
      free-form 3D ornaments could be applied on the surface of flat sheets with
      nanometer resolution. Together, these folding patterns and experimental
      techniques present a unique platform for the fabrication of metamaterials with
      unprecedented combination of physical properties and surface-driven
      functionalities.

PMID- 29209662
TI  - Prehistoric women's manual labor exceeded that of athletes through the first 5500
      years of farming in Central Europe.
AB  - The intensification of agriculture is often associated with declining mobility
      and bone strength through time, although women often exhibit less pronounced
      trends than men. For example, previous studies of prehistoric Central European
      agriculturalists (~5300 calibrated years BC to 850 AD) demonstrated a significant
      reduction in tibial rigidity among men, whereas women were characterized by low
      tibial rigidity, little temporal change, and high variability. Because of the
      potential for sex-specific skeletal responses to mechanical loading and a lack of
      modern comparative data, women's activity in prehistory remains difficult to
      interpret. This study compares humeral and tibial cross-sectional rigidity,
      shape, and interlimb loading among prehistoric Central European women
      agriculturalists and living European women of known behavior (athletes and
      controls). Prehistoric female tibial rigidity at all time periods was highly
      variable, but differed little from living sedentary women on average, and was
      significantly lower than that of living runners and football players. However,
      humeral rigidity exceeded that of living athletes for the first ~5500 years of
      farming, with loading intensity biased heavily toward the upper limb. Interlimb
      strength proportions among Neolithic, Bronze Age, and Iron Age women were most
      similar to those of living semi-elite rowers. These results suggest that, in
      contrast to men, rigorous manual labor was a more important component of
      prehistoric women's behavior than was terrestrial mobility through thousands of
      years of European agriculture, at levels far exceeding those of modern women.

PMID- 29209663
TI  - Electronic medical record alert improves HCV testing for baby boomers in primary
      care setting: adults born during 1945-1965.
AB  - Method: This project aims to implement the HCV birth cohort screening guidelines
      over a 9-month period in the primary care setting at the University of Kansas
      Health System General Internal Medicine Division. The project team measured the
      number of patients in the baby boomer population who received a one-time screen
      for HCV. An electronic medical record (EMR) intervention was implemented to
      identify baby boomers who did not have an HCV screening or diagnosis.
      Additionally, education was provided to all primary care providers in the clinic
      to increase awareness of the HCV birth cohort screening. Results: The quality
      improvement methods increased the percentage of baby boomers who obtained a one
      time screening test for HCV from a baseline of 30% to a 55% screening rate during
      the nine-month project period. Conclusion: Identifying the HCV screening needs
      and creating a visual reminder in the EMR can be used to facilitate sustainable
      awareness and improvement of screening rates. The project team recognizes that
      continued work is required to close the HCV screening care gaps in the primary
      care setting.

PMID- 29209664
TI  - The impact of health information technology on patient safety.
AB  - Since the original Institute of Medicine (IOM) report was published there has
      been an accelerated development and adoption of health information technology
      with varying degrees of evidence about the impact of health information
      technology on patient safety.  This article is intended to review the current
      available scientific evidence on the impact of different health information
      technologies on improving patient safety outcomes. We conclude that health
      information technology improves patient's safety by reducing medication errors,
      reducing adverse drug reactions, and improving compliance to practice guidelines.
      There should be no doubt that health information technology is an important tool
      for improving healthcare quality and safety. Healthcare organizations need to be
      selective in which technology to invest in, as literature shows that some
      technologies have limited evidence in improving patient safety outcomes.

PMID- 29209665
TI  - Beneficial effects of specific natural substances on oral health.
AB  - Substances that are consumed daily or occasionally may influence an individual's
      oral health. Some substances, such as alcohol, tobacco, and areca nut, adversely
      affect the oral region. However, some other substances, such as honey and green
      tea, which have antimicrobial properties, and berries, which have
      anticarcinogenic potential, exhibit beneficial effects on oral health. The
      effectiveness of synthetic drugs in maintaining oral health cannot be ignored;
      however, the benefits of synthetic drugs are associated with adverse effects and
      high costs. By contrast, the medicinal use of natural substances is associated
      with safety, affordability, and long-term benefits. In this paper, we review
      various natural substances that are potentially beneficial to oral health.

PMID- 29209666
TI  - Novel duplication mutation of the DYSF gene in a Pakistani family with Miyoshi
      Myopathy.
AB  - OBJECTIVES: To identify the underlying gene mutation in a large consanguineous
      Pakistani family.  Methods: This is an observational descriptive study carried
      out at the Department of Biochemistry, Shifa International Hospital, Quaid-i-Azam
      University, and Atta-ur-Rahman School of Applied Biosciences, National University
      of Sciences and Technology, Islamabad, Pakistan from 2013-2016. Genomic DNA of
      all recruited family members was extracted and the Trusight one sequencing panel
      was used to assess genes associated with a neuro-muscular phenotype. Comparative
      modeling of mutated and wild-type protein was carried out by PyMOL tool. 
      Results: Clinical investigations of an affected individual showed typical
      features of Miyoshi myopathy (MM) like elevated serum creatine kinase (CK)
      levels, distal muscle weakness, myopathic changes in electromyography (EMG) and
      muscle histopathology. Sequencing with the Ilumina Trusight one sequencing panel
      revealed a novel 22 nucleotide duplication (CTTCAACTTGTTTGACTCTCCT) in the DYSF
      gene (NM_001130987.1_c.897-918dup; p.Gly307Leufs5X), which results in a
      truncating frameshift mutation and perfectly segregated with the disease in this
      family. Protein modeling studies suggested a disruption in spatial configuration
      of the putative mutant protein.  Conclusion: A novel duplication of 22 bases
      (c.897_918dup; p.Gly307Leufs5X) in the DYSF gene was identified in a family
      suffering from Miyoshi myopathy. Protein homology analysis proposes a disruptive
      impact of this mutation on protein function.

PMID- 29209667
TI  - Narcolepsy in Saudi patients before and after the 2009 H1N1 vaccination. The
      experience of 2 referral centers.
AB  - OBJECTIVES: To assess the number of Saudi patients diagnosed with narcolepsy in 2
      tertiary centers before and after the introduction of the 2009 A(H1N1)pdm09
      vaccine.  Methods: We started collecting data after the first international
      report of an association between the A(H1N1)pdm09 vaccine and narcolepsy between
      January 2010 and December 2016. All patients diagnosed with narcolepsy after 2009
      were included and data were collected for 7 years to account for any possible
      delays in the diagnosis of narcolepsy.  Results: One-hundred and seventy-three
      patients with narcolepsy were identified. The majority (144 patients, 83%) had
      symptom onset before June 2009. Only 29 patients (17%) had symptom onset after
      2009. No difference in the annual number of narcolepsy cases was found  before
      and after 2009. Conclusion: Based on data obtained from 2 tertiary care sleep
      disorders center, there was no increase in the number of cases of narcolepsy
      among Saudis following the introduction of the influenza A(H1N1)pdm09
      vaccination.

PMID- 29209668
TI  - Salivary parameters among Arabian snuff (Shammah) users.
AB  - OBJECTIVES: To evaluate the salivary flow rate (SFR),  pH, and buffer capacity
      (BC) among healthy shammah users (SU) in comparison with healthy non-shammah
      users (NSU). Methods: This case-control study was conducted at the College of
      Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia between March 2016
      and May 2017. A sample of 27 SU and 30 NSU were recruited. Unstimulated saliva
      was collected and SFR, pH, and BC were determined. Dental health was assessed
      using the decay-missing-filled teeth (DMFT) index.  Results: Shammah users were
      slightly older than NSU (28.9+/-6.9 versus 24.9+/-4.3 years). Salivary flow rate 
      was not significantly different, but pH (6.68+/-0.46) and BC (5.7+/-2.07) were
      significantly lower in SU users than in NSU (7+/-0.37; p=0.002 versus 8.1+/-1.47;
      p less than 0.001). Conversely, the DMFT in SU users was significantly higher
      (7.96+/-5.17) compared to that of NSU (4.53+/-3.46; p=0.007). Salivary pH and BC
      were significantly and directly correlated (rs= 0.576). The former was
      significantly and directly correlated with SFR (rs= 0.404), but the latter was
      not. In contrast, BC inversely correlated with decay (rs= -0.385) and DMFT (rs= 
      0.399). Conclusions: Shammah use is associated with alterations in saliva quality
      (pH and BC). It is also associated with poor dental health either through a
      direct effect or mediation by altered salivary parameters.

PMID- 29209669
TI  - Comparison of alveolar ridge splitting and autogenous onlay bone grafting to
      enable implant placement in patients with atrophic jaw bones.
AB  - OBJECTIVE: To compare alveolar ridge splitting (ARS) and autogenous onlay bone
      grafting (AOBG) in atrophic jaw bones.  Methods: Forty patients were included in
      this retrospective, parallel-group study conducted at the Istanbul Medipol
      University School of Dentistry, Istanbul, Turkey, between 2012-2015. The initial
      bone thickness was measured by cone beam computed tomography (CBCT). Patients
      were allocated into ARS (n=17) and AOGB (n=23) groups on the basis of ridge
      thickness and shape. Follow-up CBCT measurements to assess horizontal bone were
      repeated 4 to 6 months post augmentation. The diameters of the implants were
      recorded. Implant bone resorption was measured at one year post implant placement
      on panoramic radiography. Surgical complications and implant survival were
      evaluated.  Results: The final bone width in the AOBG group was significantly
      higher than that in the ARS group (p=0.029). Forty-four implants were inserted in
      the AOGB group, whereas 33 implants were inserted in the ARS group. There was no
      significant difference regarding implant diameter (p=0.920). Implant survival
      rate was 93.9% in the ARS group and 93.1% in the AOGB group. Peri-implant bone
      resorption at one year was higher in the AOBG group than in the ARS group
      (p=0.032). There were minor surgical complications, including bad split and wound
      dehiscence.  Conclusion: The incidence of peri-implant bone resorption for the
      AOGB technique was higher than that for the ARS technique, but their implant
      survival rates were similar.

PMID- 29209670
TI  - Inflammatory parameters in sexually abused children.
AB  - OBJECTIVES: To investigate whether serum levels of cortisol, interleukin-6 and
      interleukin-10 differed between children with or without a sexual trauma.
      Methods: This descriptive study was conducted in the Department of Child
      Protective Service (CPS), Bursa Yuksek Ihtisas Training and Research Hospital,
      Bursa, Turkey, between May 2016 and July 2016. Three different markers (cortisol,
      interleukin-6 and interleukin-10) were used to perform this experiment. We
      included 17 children age less than 18 years old and sexually abused, and 10
      children who were not abused as a control group. The levels of cortisol,
      interleukin-6, and interleukin-10 were measured in blood samples using enzyme
      linked immunosorbent assay method. The results of the experiment were
      statistically analyzed. Results: The findings indicate that serum levels of
      interleukin-6 were higher in the sexually abused children compared with the
      control group (p=0.002). There were no significant differences in the serum
      levels of cortisol (p=0.604) and interleukin-10 (p=0.835) between the sexually
      abused children and the control group.  Conclusion: No significant differences
      were seen between the patients with or without sexual assault in terms of
      cortisol and IL-10 levels. It is found that in age-matched controls, SAC had
      higher IL-6 levels.

PMID- 29209671
TI  - Neck circumference as a marker of obesity and a predictor of cardiometabolic risk
      among Saudi subjects.
AB  - OBJECTIVES: To determine the optimal cutoff value for neck circumference (NC)
      that define overweight/obesity and assess its predictive potential for
      cardiometabolic risks (CMR) among Saudi subjects.  Methods: A cross sectional
      study of 785 adults recruited from a public health awareness campaign in Medina,
      Saudi Arabia during June 2015. Waist circumference (WC), NC, body mass index
      (BMI), blood pressure (BP), and random blood glucose (RBG) were assessed, and the
      presence of CMR were collected by a questionnaire. Pearson's correlation
      coefficients were used to evaluate the associations of NC with other
      anthropometric indices and CMR. The optimal cutoff value for NC to identify
      overweight/obesity was determined by receiver operating characteristic (ROC)
      curves. Results: There were significant correlations between NC and BMI, weight,
      WC, age, RBG, and BP. The area under the curve for NC and WC in the ROC analysis
      was 0.86 for men and 0.77 for women, and NC >=39.25 cm for men and >=34.75 cm for
      women were the best cutoff levels for identifying subjects with central obesity
      with an 89% sensitivity and a 71% specificity for men and an 80% sensitivity and
      a 65% specificity for women. These cutoff levels for NC were associated with a
      significantly increased risk for diabetes, dyslipidemia, and hypertension. 
      Conclusion: Neck circumference is positively correlated with BMI and WC, and can
      be used to identify overweight/obesity and predict CMR in Saudi individuals.

PMID- 29209672
TI  - Ultrasound-guided subcostal-posterior transversus abdominis plane block for pain
      control following laparoscopic sleeve gastrectomy.
AB  - OBJECTIVES: To investigate the analgesic effect of a subcostal-posterior
      transversus abdominis plane (TAP) block combination following laparoscopic sleeve
      gastrectomy. Methods: This study was conducted at Fatih Sultan Mehmet Educational
      and Research Hospital, Istanbul, Turkey, between March 2014 and June 2015. A
      total of 40 patients with a body mass index of 40-60 kg/m2 scheduled for
      laparoscopic sleeve gastrectomy were randomly allocated into 2 groups. Patients
      in Group I (n=20) received a bilateral subcostal TAP block, and patients in Group
      II (n=20) received a bilateral subcostal and posterior TAP block. Pain intensity
      was assessed at rest and during coughing using the visual analog scale (VAS)
      prior to and at various time points after TAP block (0 min, 30 min, 2 hours, 4
      hours, 6 hours, 12 hours, and 24 hours). Morphine consumption over 24 hours and
      time to first morphine requirement were recorded.  Results: There was no
      difference in VAS scores between groups. Morphine consumption was 6.78+/-5.95 mg
      in Group I, and 7.28+/-5.95 mg in Group II (p=0.795). Time to first morphine
      requirement was 267.22+/-303.84 min for Group I, and 207.80+/-209.81 min for
      Group II (p=0.154).  Conclusions: Subcostal-posterior TAP block provided
      equivalent analgesia to subcostal TAP block alone following laparoscopic sleeve
      gastrectomy.

PMID- 29209673
TI  - Chronic urticaria in most patients is poorly controlled. Results of the
      development, validation, and real life application of the arabic urticaria
      control test.
AB  - OBJECTIVES: To translate and linguistically validate the urticaria control test
      (UCT) to/for Arabic speakers. No Arabic version of the UCT is available to assess
      disease control in patients with chronic urticaria (CU). Secondary objectives
      were to assess disease control in Lebanese CU patients and determine influence
      factors. METHODS: This is a prospective observational study of 178 CU patients
      diagnosed during their first visit to a private Allergy/Immunology Clinic, Hotel
      Dieu de France Hospital, Beirut, Lebanon between January and December 2014.
      RESULTS: Factor analysis showed that all 4 UCT items on the Arabic version
      converged over a solution of one factor. A high internal consistency was found
      with a Cronbach's alpha of 0.824. Most patients in this study had chronic
      spontaneous urticaria (96%), of which 19% also had inducible urticaria. The
      majority was less than 40 years (67.4%), with disease duration of less than 2
      years (70.8%). Most patients used H1-antihistamines, but unfortunately, 34.3%
      used systemic glucocorticosteroids, of which 24.7% also used H1-antihistamines.
      The disease was poorly controlled in most patients (79.2%, UCT less than 12).
      Age, gender, duration, diagnosis, triggers, and/or history of atopy had no
      influence. CONCLUSION: We developed the first linguistically validated Arabic UCT
      to improve CU management in Arabic speaking patients. We also found that disease
      control was poor in most CU patients, and is unaffected by age, disease duration,
      gender, subtype, triggers, history of atopy, and/or previous treatments.

PMID- 29209674
TI  - Prevalence and determinants of antenatal depression among women attending primary
      health care centers in Western Saudi Arabia.
AB  - OBJECTIVES: To measure the prevalence of antenatal depression among pregnant
      women attending the primary health care (PHC) antenatal care clinics in Jeddah,
      Saudi Arabia and to determine associated factors. METHODS: Following a cross
      sectional study design, 320 pregnant women attending the antenatal care clinics
      in the Ministry of Health PHC Centers in Jeddah, Saudi Arabia between January 1st
      2017 and February 15th 2017 were interviewed. A self-administered questionnaire
      used for data collection asked about socio-demographic variables and included the
      Edinburgh Postnatal Depression Scale. RESULTS:   The most common contributor was
      the  harming herself (mean+/-SD, 2.7+/-0.60). Factors significantly associated
      with depression among participants were the number of daughters, previous
      diagnosis of depression, and financial problems. CONCLUSIONS: The prevalence of
      antepartum depression among pregnant women in Jeddah is 57.5%, and the greatest
      contributor is the thought of harming herself.

PMID- 29209675
TI  - Serotype prevalence and antibiotic susceptibility patterns of pneumococcal
      isolates in Zunyi city, China.
AB  - OBJECTIVES: To assess the serotype distribution and antimicrobial susceptibility
      of pneumococci isolated from inpatients of all ages suspected of having bacterial
      infections. METHODS: In this retrospective study, pneumococcal isolates were
      consecutively collected  from the Third Affiliated Hospital of Zunyi Medical
      University, in Zunyi city, China, between January 2014 and December 2016.
      Pneumococci were identified using routine microbiological assays. We performed
      antimicrobial susceptibility analyses using the bacteria
      identification/susceptibility system VITEK2 and E-tests. Capsular types of all
      isolates were determined by multiplex polymerase chain reaction. RESULTS: We
      identified 778 pneumococcal isolates. Serotypes 19F, 6A/6B, 19A, 23F, and 15B/15C
      were the most prevalent strains, accounting for 71.5% (556/778) of all isolates.
      Data show that 409 (70.4%) isolates could be covered by the PCV13 vaccine in
      children less than 2 years old. Irrespective of serotypes, 747 (96%) isolates
      were sensitive to penicillin, while 720 to 778 (90% to 100%) isolates were not
      susceptible to erythromycin, tetracycline, and trimethoprim/sulfamethoxazole. For
      isolates resistant to penicillin, ceftriaxone, cefotaxime, and meropenem, 22 to
      39 (70% to 81.25%) strains belonged to PCV13 serotypes. CONCLUSION: We found a
      substantial increase in the annual number of pneumococcal isolates since 2014.
      The theoretical impact of PCV13 was high in children less than 2 years old, and
      penicillin might be effective against pneumococcal infections in this region.

PMID- 29209676
TI  - Fatal butane toxicity and delayed onset of refractory ventricular fibrillation.
AB  - A 30-year-old male was presented to the Emergency Department (ED) by the
      Emergency Medical Services (EMS). He was found unconscious but breathing
      normally, and had a seizure for more than 30 minutes. He was no previous history
      of systemic disease, previous operation, medication and any known allergy.
      According to the witnesses, he was alone in the coffee shop, and besides him was
      a lighter refill canister containing 250 ml extra purified butane gas, and he
      suddenly collapsed and had seizure. Six hours later, he developed ventricular
      fibrillation and he was not responding to amiodarone infusion, and 4 times
      defibrillation and cardioversion. He died after 45 minutes of resuscitation.

PMID- 29209677
TI  - Laparoscopic-assisted endorectal pull-through for Hirschsprung's disease. A
      retrospective study.
AB  - OBJECTIVES: To summarize the efficacy of the laparoscopic-assisted transanal
      endorectal pull-through procedure for Hirschsprung's disease (HD). METHODS:
      Between May 2006 and May 2013, 22 children with HD undergoing laparoscopic
      assisted endorectal pull-through procedures were retrospectively analyzed. The
      operative time, pathology, intraoperative blood loss, recovery time for
      gastrointestinal function, postoperative hospital stay, complications, and
      defecation functions of the patients were analyzed. RESULTS: The procedure was
      successfully completed in all 22 patients without conversion to open surgery. The
      operative time was 105-190 minutes (mean, 160.4 minutes), and the intraoperative
      blood loss was 20-50 ml. The mean time for the recovery of gastrointestinal
      function was 22 hours, and the mean postoperative hospital stay was 8 days. All
      patients had 1-3 defecations per day at 6 months postoperatively without
      constipation, soiling, or stoma stenosis. CONCLUSION: The laparoscopic-assisted
      transanal-endorectal pull-through procedure is a safe and feasible technique for
      patients with HD.

PMID- 29209678
TI  - A rare complication of metastatic lung disease treatment.
AB  - [No Abstract Available].

PMID- 29209679
TI  - Comparing i-gel and Ambu AuraOnce laryngeal mask airway in pediatric patients.
AB  - [No Abstract Available].

PMID- 29209680
TI  - Dengue fever in Saudi Arabia.
AB  - [No Abstract Available].

PMID- 29209681
TI  - Is there a low prevalence of Helicobacter pylori infection in Jordanian patients
      with gastric cancer?
AB  - [No Abstract Available].

PMID- 29209682
TI  - Erratum: Ambu AuraOnce versus i-gel laryngeal mask airway in infants and children
      undergoing surgical procedures. A randomized controlled trial.
AB  - [No Abstract Available].

PMID- 29209684
TI  - Videolaparoscopic cholecystectomy in patients with previous abdominal surgery.
      Personal experience and literature review.
AB  - OBJECTIVES: Laparoscopic cholecystectomy (LC) is today the "gold standard"
      treatment of gallbladder stones. Role of LC is still debated in the presence of
      abdominal scars due to the frequent post-operative adhesions which make access to
      the peritoneal cavity difficult. This study aim to assess role and outcomes of LC
      on a previous abdominal surgery on the scarred abdomen. MATERIALS AND METHODS: We
      have carried out a retrospective study on 499 consecutive patients who had
      undergone LC from 2009 to 2015; 21 of these (4.2%) undergone previous abdominal
      surgery. In all 21 cases the pneumoperitoneum was established with Veress needle
      at the Palmer's point and the procedure was carried out after adhesiolysis in 62%
      of cases. RESULTS: The mean operative time was 79+/-12 minutes; none of the
      patients with previous abdominal surgery required conversion to open
      cholecystectomy and there were no postoperative complications related to Veress
      introduction or to the adhesiolysis. The difficult dissection and adhesiolysis
      were more frequent in the patients with upper abdomen scar (62%) respect to lower
      abdomen scar (38%). CONCLUSIONS: Patients with scarred abdomen for previous
      abdominal surgery had obviously more adhesions in the abdomen than patients
      without preceding surgery, but today previous abdominal surgery should not
      constitutes absolute contraindications to LC. Moreover, patients with previous
      lower abdominal incisions had fewer adhesions in the upper abdomen than did
      patients with upper incision and, probably, in these cases adhesiolysis is
      unnecessary, if the surgical field is well exposed whereas adhesiolysis is
      mandatory when the adhesions are thick and widespread, to the anterior and
      posterior abdominal wall.

PMID- 29209683
TI  - [Construction and validation of a tool for the evaluation of environmental risks
      and limitations to the manual handling of loads: cross-sectional study].
AB  - INTRODUCTION: The manual handling of loads has a strong impact on many types of
      work. All health professionals, due to their job, are subjected to a high risk of
      disease from the manual handling of loads. TARGET: The purpose of our work has
      been therefore the construction and the validation of a specific tool for the
      evaluation of both environmental risks and individual limitations of the manual
      handling of loads / patients. MATERIALS AND METHODS: The questionnaire we created
      is composed of two main sections: the first section includes the registry card of
      the operator personal data while the second section, consisting of eleven items
      it is further organized into two sections/parts. The first part consists of four
      items about environmental risk factors, while the second part consists of seven
      items about generic limitations and the assessment of pain from manual handling
      of loads. RESULTS: The operators'health nurses, including those ones with a
      coordination responsibility, that are available in the structure are 704 while
      the response rate to the questionnaire was of 93.18%. The test-retest showed
      optimal values of the intra-class correlation coefficient (0.843) so
      demonstrating the absence of measurement errors in the two administrations. The
      values related to the internal consistency of the two sections of the
      questionnaire were greater than 0.80that also demonstrated the internal stability
      of the questionnaire. CONCLUSIONS: The tool we described therefore is to be
      intended as a means of assessment for environmental risks, restrictions on
      movement of loads and pain associated with the task.

PMID- 29209685
TI  - [Knowledge, attitude and behavior towards oral health: gender differences between
      parents].
AB  - OBJECTIVES: The aim of this study is to compare the results of a survey carried
      out on a sample of mothers and fathers about the knowledge and personal attitudes
      towards their own oral health and in terms of attention to that of their
      children. Mutual analogy and cognitive and behavioral differences between parents
      have been evaluated; in particular as the early assumption of a healthy lifestyle
      can influence the proper development of their children. MATERIALS AND METHODS:
      This survey was conducted using a paper questionnaire distributed to a population
      of parents, men and women, in several private dental practices in Rome. The study
      lasted about three months. RESULTS: The results obtained from this study show
      that values obtained by mothers and fathers are essentially equivalent, there are
      no statistically significant differences (p> 0.05). CONCLUSIONS: This study has
      shown that there are no significant thinking and behavioral differences between
      parents regarding their oral hygiene and that of their children. Both parents
      have been shown to recognize the importance of continuous monitoring and to be
      aware of techniques and oral hygiene aids suitable for adults and children,
      although this knowledge is not always applied in daily lifestyles and oral
      hygiene.

PMID- 29209686
TI  - Neuromuscular taping enhances hand function in patients with systemic sclerosis:
      a pilot study.
AB  - Hand functioning is often impaired in patients with Systemic sclerosis.
      Neuromuscular Taping is a novel application of tape able to improve functioning.
      The aim of this study was to evaluate the possible role of this application in
      the hand functionality of patients with Systemic sclerosis. Women with a
      diagnosis of SSc has been recruited and evaluated using different scales before
      and immediately after NMT application and after one, three and six months. Fifty
      three women has been evaluated and Cochin Hand Functional Disability scale, Hand
      Mobility in Sclerodermia, Modified Rodnan Skin Score and Dreiser Algo -
      Functional Index scores showed statistical significant differences during all the
      period; moreover a reduction of pain and Raynaud Phenomenon's and an improvement
      of finger flexion has been observed. Application of NMT in patients with Systemic
      sclerosis have showed beneficial effect and future studies are needed to confirm
      these results.

PMID- 29209687
TI  - High risk of brain tumors in military personnel: a case control study.
AB  - Scientific literature suggests a relationship between military occupation and the
      development of brain tumors, but no italian study has investigated on the impact
      of this job on the brain cancer morbidity. In this a study information were
      obtained from patients recruited in the Neurosurgical Department of the
      University-Hospital of Pisa, Italy, from 1990 to 1999. The study has been
      conducted as a case-control study. 161, newly diagnosed cases of brain tumors
      (glioma and meningiomas, histologically confirmed), were recruited, such as 483
      controls (with other non tumoral neurologic diseases: trauma, hemorrhagic brain
      disorders, aneurism, etc), by matching cases and controls (1:3), for age (+/- 5
      years) and gender. Cases and controls were interviewed in the Neurosurgical
      Department, University-Hospital of Pisa, Italy, and the occupational histories of
      cases and controls were compared. Cases and controls have showed a statistically
      significant difference, based on their occupation (military vs. non-military
      occupation). A statistically significant association was seen between brain
      tumors and military occupation among evaluated patients (p=0.013). Further
      studies regarding this population group are needed, to determine the causes for
      the increased risk of this cancer. Furthermore, a subsequent reevaluation in
      other patients collected in more recent years will be needed to evaluate the
      trend of this association.

PMID- 29209689
TI  - Could a vitamin D deficiency cause a combined long-term FEV1 and bone mineral
      density deterioration in female asthmatics?
AB  - OBJECTIVES: We already know that asthma is associated to osteoporosis/osteopenia
      and characterized by an accelerated lung function decline. Our study aimed at
      assessing whether lung function decline and bone mineral density (BMD)
      deterioration in time were associated in a group of female long-standing
      asthmatics. We also tried to understand whether these two aspects were related to
      ICS treatment and vitamin D levels. METHODS: 35 female asthmatics were
      retrospectively analysed. Results of methacholine challenge test at asthma onset,
      FEV1%, bone density scan at moment of recruitment and after at least 5years later
      were considered. RESULTS: A significant positive relationship between femoral-t
      scores changes and FEV1 decline was found after a median follow-up time of 7 [6
      9] years (r=0.43;p=0.04). Femoral-t-score variations and vitamin D values were
      also significantly related (r=0.669;p=0.024). Furthermore, we found that FEV1
      decline was worse in subjects with lower vitamin D levels (-57.5[-80.4
      35.9]ml/year), compared to those with normal vitamin D rates (12[-16
      23.6]ml/year;p=0.055). Femoral/vertebral t-score changes, as well as FEV1,
      decline were not associated to the use of medium/high ICS doses when compared to
      subjects treated with low ICS dosages. CONCLUSIONS: FEV 1 decline and BMD
      deterioration in time observed in a group of female asthmatics were associated;
      low vitamin D levels may be the link.

PMID- 29209688
TI  - Correlation between benzene and testosterone in workers exposed to urban
      pollution.
AB  - AIM: Many studies have examined the effects of benzene on testosterone. The
      purpose of this study was to evaluate the possible correlation between the blood
      levels of benzene and the levels of testosterone. MATERIALS AND METHODS: The
      study involved a group of 148 subjects. For every worker have been made out a
      blood sample for the evaluation of benzene and testosterone levels and an urine
      analysis for the evaluation of the levels of trans, trans-muconic acid and S
      phenylmercapturic acid. We estimated the Pearson correlation coefficient between
      the variables in the sample and the urinary metabolites, age, length of service,
      gender, BMI. For the analysis of the major confounding factors it was performed a
      multiple linear regression. RESULTS: The Pearson correlation coefficiet showed:
      1. a significant inverse correlation between the S-phenyl mercapturic acid and
      free testosterone; 2. a significant direct correlation between trans-trans
      muconic acid and BMI. After dividing the sample according to the median of blood
      benzene (161.0 ng / L), Pearson correlation coefficient showed a significant
      inverse correlation between the S-phenyl mercapturic acid and free testosterone
      in the group with values below this median. CONCLUSIONS: Our results, to be
      considered preliminary, suggest that occupational exposure to low levels of
      benzene, present in urban pollution, affect the blood levels of testosterone.
      These results need to be confirmed in future studies, with the eventual
      possibility of including more specific fertility tests.

PMID- 29209690
TI  - Prosthetic rehabilitation involving the use of implants following a fibula free
      flap reconstruction in the treatment of Osteosarcoma of the maxilla: a case
      report.
AB  - INTRODUCTION: Osteosarcoma is an aggressive primary bone tumor composed of
      connective tissue cells directly producing osteoid and bone. Prosthetic
      rehabilitations in post-oncological patients after bone reconstruction are not
      substantially different than those of patients affected by severe atrophy of
      upper or lower jaw after bone reconstruction. The treatment for patients with a
      malignant neoplasia of the oral cavity requires multidisciplinary approach by a
      team of different specialists that follow the patient through the phases of
      diagnosis, therapy and oral rehabilitation. Reconstructive surgery of jaws using
      vascularized free flap allows a significant gain of tissues that enables a
      successful final prosthetic rehabilitation. In fact main prosthetics difficulties
      result from lack of hard and soft tissues in affected area. Reconstructed
      patients have a greater ease of care management. CASE PRESENTATION: A 25-year-old
      Caucasian male was diagnosed with chondroblastic osteosarcoma of the pre-maxilla.
      The patient initially noticed the displacement of his maxillary incisors with
      progression into a definite swelling of the pre-maxillary a month later.
      Computerized Tomographic Scan and Radionuclide Bone Scan revealed the absence of
      both distant metastasis and regional nodal involvement. A biopsy and subsequent
      histopathology examination confirmed the lesion as being a chondroblastic type of
      osteosarcoma. The case study directed us to rehabilitate the patient by implant
      supported prosthesis consisting 3 different components: a titanium base screwed
      on implants, a titanium structure (primary structure) assembled on the base and a
      composite coatedstructure (secondary structure) that reproduced teeth and gum. At
      surgery, we proceeded placing 6 dental implants in 1.4, 1.3 1.2, 2.1, 2.2 and 2.4
      positions. Contextually was performed a bone graft using particulate bone and
      collagen membranes. CONCLUSIONS: Prosthetic rehabilitation in Maxillofacial
      Osteosarcoma treatment is an hard challenge for prosthodontist due to anatomic
      conditions of this kind of patients. Dental implants play a crucialrole in the
      therapy of patients affected by malignancies in the head-and-neck region. The
      goal of implant rehabilitationis to improve the quality of life of these patients
      by allowing proper retention of removable prostheses and a reduction in the load
      placed on vulnerable soft tissues. Today prosthetically guided rehabilitation
      represents the main rehabilitation protocol in prosthodontics, especially in
      those oncological patients with relevant lost of tissues and modified anatomy.

PMID- 29209691
TI  - A case of Infective Endocarditis due to Salmonella enterica phagetype 35. First
      report.
AB  - Infective Endocarditis (IE) has high morbidity and mortality. To date, in
      addition to classic Gram-positive pathogens were isolated exigent Gram negative
      bacteria responsible of endocarditis as A. baumannii, A. lwoffii, C. burnetii,
      Bartonella, Chlamydia and Legionella. We report our experience about the
      isolation of Salmonella enterica phagetype 35 (PT35) from blood heart cavity of a
      74-year-old woman after having consumed a portion of baked pasta bought in a
      rotisserie. Cardiovascular infections due to Salmonella enterica are infrequently
      reported, so their clinical features, prognosis, and optimal treatment are not
      completely known. To the best of our knowledge, after careful evaluation of
      existing literature, this is the first report of endocarditis due S. enterica PT
      35.

PMID- 29209692
TI  - Hackathon Public Health.
AB  - BACKGROUND: It is necessary to implement current teaching in the healthcare and
      university sector by promoting new tools for the enhancement of public health,
      bearing in mind that some health determinants seek to create a context in which
      to present their own idea of innovative Startup, can represent the opportunity to
      give your professional contribution to the development of another's idea or to
      propose an improved solution to the private business. On the other hand,
      networking with companies and networking between training participants will allow
      us to recognize the importance of demonstrating their diverse skills as a key
      element to create a successful Startup or to implement the activities of a
      reality already consolidated. METHODS: This paper describes the research protocol
      of a Hackathon Public Health (HPH) teaching methodology aimed at: a) increasing
      public health knowledge; b) changing the proactive approach of the healthcare
      provider, especially by increasing the sectoral training activity; c) to promote
      educational and training activities in Italian regions. The subjects involved
      will be healthcare professionals (doctors, nurses, health professions,
      psychologists, biologists, assistants in training) who are selected to receive or
      not the intervention through the implementation of a HPH which also includes
      training activity. CONCLUSIONS: HPH is an innovation in the national health
      landscape, with the aim of creating environments and training policies aimed at
      promoting proper clinical risk management as part of the continuous improvement
      of the quality of healthcare organizations and proper training activities.

PMID- 29209693
TI  - Health self-perception in patient with Crohn's disease: a web survey.
AB  - BACKGROUND: Crohn's Disease (CD) has an incidence on the physical and
      psychological autonomy of the patient, such as to alter their daily life. The
      impact of the disease on the daily life of the patients is related to the
      symptoms and complications of the disease. Patient autonomy and participation in
      social and work life are the goals that nurses must reach for patients with CD to
      improve their quality of life. AIM: To measure the perception of the health of
      people with a diagnosis of CD. METHOD: Review of the literature on PubMed, and
      internet sites. Administration on the web of the standardised questionnaire Short
      Form Health Survey (SF-12). RESULTS: A total of 228 patients with CD completed
      valid questionnaires and were enrolled. The SF-12 questionnaire scores make it
      possible to build a physical health index (PCS) with a median value of 36,10 (min
      33,8; max 42,4) and mental health index (MCS) with a median value of 36,04 (min
      28.5; max 38,4). There were statistically significant data related to the
      achievement of the degree with median 41.9 (min 35,1; max 48,4) compared to non
      graduates with a p<0.001 and in relation to the employment level (median 37.9
      min/max 34,7/46,7) compared to unemployed and inactive with a p = 0.03.
      CONCLUSION: Despite the inevitable complications of the disease (intestinal and
      extra-intestinal symptoms), most of our sample did not exhibit significant
      physical limitations (surgical intervention, stomach packaging which generally
      causes a decrease in libido in both male and female patients ). The nurse cares
      for a patient with CD must have not only technical skills and specialist skills,
      but a holistic vision of the patient. Despite some findings in this study, this
      research orientation deserves more attention.

PMID- 29209694
TI  - Workers safety in public psychiatric services: problems, laws and protections.
AB  - The dramatic case of murder of a psychiatrist during her service in her public
      office (Centro di Salute Mentale of Bari-Liberta) has led the authors to reflect
      on the safety of workplaces, in detail of public psychiatric services. It is in
      the light of current legislation, represented by the Legislative Decree of April
      9th, 2008 no. 81, which states the implementing rules of Law 123/2007. In
      particular, the Authors analyzed the criticalities of the application of this
      Law, with the aim of safeguarding the health and safety of the workers in all
      psychiatric services (nursing departments, outpatient clinics, community centers,
      day care centers, etc.). The Authors suggest the need to set up an articulated
      specific organizational system of risk assessment of psychiatric services, that
      can prevent and protect the workers from identified risks, and finally to ensure
      their active participation in prevention and protection activities, in absence of
      which specific profiles of responsibility would be opened up to the employers.

PMID- 29209695
TI  - Cosmetic surgery for children and adolescents. Deontological and bioethical
      remarks.
AB  - The only interventions deemed ethically acceptable are those that serve the
      "objective interest" of the minors involved from the standpoint of and conducive
      to sound mental health and balance in a patient's teenage years; by the same
      token, disproportionate interventions (e.g. overly invasive or pointlessly
      risky), or all those deemed unsuitable with regards to a poor cost-benefit ratio
      are viewed as unacceptable. In the process of considering the best interest of
      the minors involved, a wide array of factors come into play, such as: age,
      maturity, psychological and emotional conditions, motivations put forth by the
      underage patient, the opportunity to procrastinate the operation: parents, who
      are naturally entitled to give consent to the surgical procedures, and physicians
      are primarily liable to safeguard and act in the minor's best interest. The
      authors attempt to lay out how medical science has evolved over the past century,
      and aim to set forth an array of considerations centered on cosmetic surgery for
      adolescents.

PMID- 29209696
TI  - Serial dependencies act directly on perception.
AB  - There is good evidence that biological perceptual systems exploit the temporal
      continuity in the world: When asked to reproduce or rate sequentially presented
      stimuli (varying in almost any dimension), subjects typically err toward the
      previous stimulus, exhibiting so-called "serial dependence." At this stage it is
      unclear whether the serial dependence results from averaging within the
      perceptual system, or at later stages. Here we demonstrate that strong serial
      dependencies occur within both perceptual and decision processes, with very
      little contribution from the response. Using a technique to isolate pure
      perceptual effects (Fritsche, Mostert, & de Lange, 2017), we show strong serial
      dependence in orientation judgements, over the range of orientations where
      theoretical considerations predict the effects to be maximal. In a second
      experiment we dissociate responses from stimuli to show that serial dependence
      occurs only between stimuli, not responses. The results show that serial
      dependence is important for perception, exploiting temporal redundancies to
      enhance perceptual efficiency.

PMID- 29209698
TI  - Articulatory Kinematic Characteristics Across the Dysarthria Severity Spectrum in
      Individuals With Amyotrophic Lateral Sclerosis.
AB  - Purpose: The current study investigated whether articulatory kinematic patterns
      can be extrapolated across the spectrum of dysarthria severity in individuals
      with amyotrophic lateral sclerosis (ALS). Method: Temporal and spatial
      articulatory kinematic data were collected using electromagnetic articulography
      from 14 individuals with dysarthria secondary to ALS and 6 typically aging
      speakers. Speech intelligibility and speaking rate were used as indices of
      severity. Results: Temporal measures (duration, speed of articulators) were
      significantly correlated with both indices of severity. In speakers with
      dysarthria, spatial measures were not correlated with severity except in 3
      measures: tongue movement displacement was more reduced in the anterior-posterior
      dimension; jaw movement distance was greater in the inferior-superior dimension;
      jaw convex hull area was larger in speakers with slower speaking rates. Visual
      inspection of movement trajectories revealed that overall spatial kinematic
      characteristics in speakers with severe dysarthria differed qualitatively from
      those in speakers with mild or moderate dysarthria. Unlike speakers with
      dysarthria, typically aging speakers displayed variable tongue movement and
      minimal jaw movement. Conclusions: The current study revealed that spatial
      articulatory characteristics, unlike temporal characteristics, showed a
      complicated pattern across the severity spectrum. The findings suggest that
      articulatory characteristics in speakers with severe dysarthria cannot simply be
      extrapolated from those in speakers with mild-to-moderate dysarthria secondary to
      ALS.

PMID- 29209697
TI  - False Belief Development in Children Who Are Hard of Hearing Compared With Peers
      With Normal Hearing.
AB  - Purpose: This study investigates false belief (FB) understanding in children who
      are hard of hearing (CHH) compared with children with normal hearing (CNH) at
      ages 5 and 6 years and at 2nd grade. Research with this population has
      theoretical significance, given that the early auditory-linguistic experiences of
      CHH are less restricted compared with children who are deaf but not as complete
      as those of CNH. Method: Participants included CHH and CNH who had completed FB
      tasks as part of a larger multicenter, longitudinal study on outcomes of children
      with mild-to-severe hearing loss. Both cross-sectional and longitudinal data were
      analyzed. Results: At age 5 years, CHH demonstrated significant delays in FB
      understanding relative to CNH. Both hearing status and spoken-language abilities
      contributed to FB performance in 5-year-olds. A subgroup of CHH showed protracted
      delays at 6 years, suggesting that some CHH are at risk for longer term delays in
      FB understanding. By 2nd grade, performance on 1st- and 2nd-order FBs did not
      differ between CHH and CNH. Conclusions: Preschool-age CHH are at risk for delays
      in understanding others' beliefs, which has consequences for their social
      interactions and pragmatic communication. Research related to FB in children with
      hearing loss has the potential to inform our understanding of mechanisms that
      support social-cognitive development, including the roles of language and
      conversational access.

PMID- 29209699
TI  - The First Step to Early Intervention Following Diagnosis: Communication in
      Pediatric Hearing Aid Orientation Sessions.
AB  - Purpose: This preliminary study aimed to explore communication processes and
      information exchange in pediatric hearing aid orientation (HAO) sessions.
      Effective information exchange in such sessions is crucial to support appropriate
      hearing aid use. Method: Using a qualitative sociolinguistic framework, we
      recorded and analyzed 5 HAO sessions between 2 audiologists and 5 caregivers of
      children who had just been fitted with hearing aids. We also conducted
      semistructured interviews with the audiologists and caregivers and analyzed these
      using content analysis. Results: By necessity, audiologists provide a significant
      amount of information about hearing aids to caregivers in HAO sessions. Although
      caregivers in our study recalled and understood certain points such as the
      importance of not getting the hearing aids wet, crucial information about
      insertion and cleaning was often not recalled. Some caregivers misunderstood how
      the hearing aids would assist their child. Conclusions: Caregivers need time to
      practice and absorb the information given, particularly given the emotional
      aspects associated with the diagnosis and "switch-on." There is a need to revisit
      approaches to information giving, which align with the ongoing early intervention
      process. We offer some suggestions for improving HAO sessions and information
      giving about hearing aids.

PMID- 29209700
TI  - Early Development of Emotional Competence (EDEC) Assessment Tool for Children
      With Complex Communication Needs: Development and Evidence.
AB  - Purpose: This article introduces and provides initial data supporting "The Early
      Development of Emotional Competence (EDEC): A tool for children with complex
      communication needs (CCNs)." The EDEC was developed to raise awareness about the
      relation of language and emotional competence and to maximize the likelihood that
      intervention includes language to discuss emotions in ways that are consistent
      with the values and goals of the family. Method: First, the theoretical and
      clinical foundations of the EDEC development were discussed. Then, a description
      of preferred translation practices was provided, with examples of Korean and
      Mandarin Chinese translations. Finally, initial data from a pilot study with two
      sociocultural communities (i.e., 10 American and 10 Korean mothers of children
      developing typically) were presented to demonstrate the potential of the tool.
      Results: The pilot test offered preliminary support for the sensitivity of the
      EDEC. The tool solicited responses reflecting cultural differences between
      American and Korean mothers' perception of a child's emotional skills and mother
      child conversation about emotions as predicted based on many cross-cultural
      studies in emotion. Conclusions: The information elicited from the EDEC shows
      promise for enabling culturally natural conversation about emotions with
      appropriate vocabulary and phrases in their augmentative and alternative
      communication systems. Supplemental Materials:
      https://doi.org/10.23641/asha.5643076.

PMID- 29209701
TI  - Factors Associated With Depression in Patients With Tinnitus and Hyperacusis.
AB  - Purpose: The purpose of this study was to assess factors associated with
      depression for patients with tinnitus and hyperacusis. Method: Data were gathered
      from the records of 620 consecutive patients who sought help concerning their
      tinnitus or hyperacusis from an audiology clinic in the United Kingdom. Results:
      One third of the patients had borderline abnormal or abnormal scores on the
      Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Linear
      regression models showed that HADS-D scores were related to scores for tinnitus
      handicap, tinnitus loudness, and uncomfortable loudness levels. Mediation
      analyses showed that (a) the influence of tinnitus handicap scores on HADS-D
      scores was mainly mediated via the effects of insomnia, hyperacusis, and anxiety;
      (b) the influence of tinnitus loudness scores on HADS-D scores was fully mediated
      via the effects of tinnitus handicap, insomnia, hyperacusis handicap, and
      anxiety; (c) and the small influence of uncomfortable loudness levels on HADS-D
      scores was fully mediated by hyperacusis handicap and anxiety. Conclusion: Those
      involved in the management of patients with tinnitus and/or hyperacusis should
      use a wide range of instruments to assess the full impact of tinnitus on a
      patient's life and should be prepared to refer a patient for treatment for
      depression, especially when the patient has anxiety, hyperacusis, and/or
      insomnia.

PMID- 29209702
TI  - Body-on-a-Chip Reveals Multitissue Interactions During Drug Exposure.

PMID- 29209703
TI  - The Success of State Newborn Screening Policies for Critical Congenital Heart
      Disease.

PMID- 29209705
TI  - Heart Failure Survey Is a First in FDA's Device Innovation Effort.

PMID- 29209704
TI  - High-Cutoff Hemodialysis in Myeloma Cast Nephropathy.

PMID- 29209706
TI  - Support for Treating Opioid Addiction With Medication.

PMID- 29209707
TI  - Treatment for Aggressive Lymphoma.

PMID- 29209709
TI  - Treating Specific Variants Causing Cystic Fibrosis.

PMID- 29209710
TI  - "Hopefully . . ."

PMID- 29209711
TI  - The FDA's Expedited Programs and Clinical Development Times for Novel
      Therapeutics, 2012-2016.

PMID- 29209712
TI  - Vitamin D Supplementation and Upper Respiratory Tract Infections in Children.

PMID- 29209713
TI  - Length of Stay After Overlapping Surgery.

PMID- 29209714
TI  - The Future of Radiology.

PMID- 29209715
TI  - The Future of Radiology.

PMID- 29209716
TI  - Vitamin D Supplementation and Upper Respiratory Tract Infections in Children
      Reply.

PMID- 29209717
TI  - Length of Stay After Overlapping Surgery-Reply.

PMID- 29209719
TI  - JAMA Network Articles of the Year.

PMID- 29209718
TI  - The Future of Radiology-Reply.

PMID- 29209720
TI  - Association of US State Implementation of Newborn Screening Policies for Critical
      Congenital Heart Disease With Early Infant Cardiac Deaths.
AB  - Importance: In 2011, critical congenital heart disease was added to the US
      Recommended Uniform Screening Panel for newborns, but whether state
      implementation of screening policies has been associated with infant death rates
      is unknown. Objective: To assess whether there was an association between
      implementation of state newborn screening policies for critical congenital heart
      disease and infant death rates. Design, Setting, and Participants: Observational
      study with group-level analyses. A difference-in-differences analysis was
      conducted using the National Center for Health Statistics' period linked
      birth/infant death data set files for 2007-2013 for 26 546 503 US births through
      June 30, 2013, aggregated by month and state of birth. Exposures: State policies
      were classified as mandatory or nonmandatory (including voluntary policies and
      mandates that were not yet implemented). As of June 1, 2013, 8 states had
      implemented mandatory screening policies, 5 states had voluntary screening
      policies, and 9 states had adopted but not yet implemented mandates. Main
      Outcomes and Measures: Numbers of early infant deaths (between 24 hours and 6
      months of age) coded for critical congenital heart disease or other/unspecified
      congenital cardiac causes for each state-month birth cohort. Results: Between
      2007 and 2013, there were 2734 deaths due to critical congenital heart disease
      and 3967 deaths due to other/unspecified causes. Critical congenital heart
      disease death rates in states with mandatory screening policies were 8.0 (95% CI,
      5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100
      000 births (n = 13) in 2013 (for births by the end of July); for
      other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per
      100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n
      = 21) in 2013. Early infant deaths from critical congenital heart disease through
      December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute
      decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after states
      implemented mandatory screening compared with prior periods and states without
      screening policies. Early infant deaths from other/unspecified cardiac causes
      declined by 21.4% (95% CI, 6.9%-33.7%), with an absolute decline of 3.5 (95% CI,
      3.2-3.8) deaths per 100 000 births. No significant decrease was associated with
      nonmandatory screening policies. Conclusions and Relevance: Statewide
      implementation of mandatory policies for newborn screening for critical
      congenital heart disease was associated with a significant decrease in infant
      cardiac deaths between 2007 and 2013 compared with states without these policies.

PMID- 29209723
TI  - Active Surveillance for Prostate Cancer.

PMID- 29209722
TI  - Association Between Treatment by Locum Tenens Internal Medicine Physicians and 30
      Day Mortality Among Hospitalized Medicare Beneficiaries.
AB  - Importance: Use of locum tenens physicians has increased in the United States,
      but information about their quality and costs of care is lacking. Objective: To
      evaluate quality and costs of care among hospitalized Medicare beneficiaries
      treated by locum tenens vs non-locum tenens physicians. Design, Setting, and
      Participants: A random sample of Medicare fee-for-service beneficiaries
      hospitalized during 2009-2014 was used to compare quality and costs of hospital
      care delivered by locum tenens and non-locum tenens internal medicine physicians.
      Exposures: Treatment by locum tenens general internal medicine physicians. Main
      Outcomes and Measures: The primary outcome was 30-day mortality. Secondary
      outcomes included inpatient Medicare Part B spending, length of stay, and 30-day
      readmissions. Differences between locum tenens and non-locum tenens physicians
      were estimated using multivariable logistic regression models adjusted for
      beneficiary clinical and demographic characteristics and hospital fixed effects,
      which enabled comparisons of clinical outcomes between physicians practicing
      within the same hospital. In prespecified subgroup analyses, outcomes were
      reevaluated among hospitals with different levels of intensity of locum tenens
      physician use. Results: Of 1 818 873 Medicare admissions treated by general
      internists, 38 475 (2.1%) received care from a locum tenens physician; 9.3%
      (4123/44 520) of general internists were temporarily covered by a locum tenens
      physician at some point. Differences in patient characteristics, demographics,
      comorbidities, and reason for admission between locum tenens and non-locum tenens
      physicians were not clinically relevant. Treatment by locum tenens physicians,
      compared with treatment by non-locum tenens physicians (n = 44 520 physicians),
      was not associated with a significant difference in 30-day mortality (8.83% vs
      8.70%; adjusted difference, 0.14%; 95% CI, -0.18% to 0.45%). Patients treated by
      locum tenens physicians had significantly higher Part B spending ($1836 vs $1712;
      adjusted difference, $124; 95% CI, $93 to $154), significantly longer mean length
      of stay (5.64 days vs 5.21 days; adjusted difference, 0.43 days; 95% CI, 0.34 to
      0.52), and significantly lower 30-day readmissions (22.80% vs 23.83%; adjusted
      difference, -1.00%; 95% CI -1.57% to -0.54%). Conclusions and Relevance: Among
      hospitalized Medicare beneficiaries treated by a general internist, there were no
      significant differences in overall 30-day mortality rates among patients treated
      by locum tenens compared with non-locum tenens physicians. Additional research
      may help determine hospital-level factors associated with the quality and costs
      of care related to locum tenens physicians.

PMID- 29209721
TI  - Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis
      Independence Among Patients With Myeloma Cast Nephropathy: A Randomized Clinical
      Trial.
AB  - Importance: Cast nephropathy is the main cause of acute kidney injury in multiple
      myeloma and persistent reduction in kidney function strongly affects prognosis.
      Strategies to rapidly remove nephrotoxic serum-free light chains combined with
      novel antimyeloma agents have not been evaluated prospectively. Objective: To
      compare the hemodialysis independence rate among patients newly diagnosed with
      myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer
      (with very large membrane pores and high permeability to immunoglobulin light
      chains) or a conventional high-flux dialyzer (with small pores and lower
      permeability). Design, Setting, and Participants: Randomized clinical trial
      involving 98 patients with biopsy-proven myeloma cast nephropathy requiring
      hemodialysis treated at 48 French centers between July 2011 and June 2016; the
      final date of follow-up was June 29, 2016. Interventions: Intensive hemodialysis
      (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46
      patients) or a conventional high-flux dialyzer (48 patients). All patients
      received the same chemotherapy regimen of bortezomib and dexamethasone. Main
      Outcomes and Measures: Primary end point was hemodialysis independence at 3
      months; secondary end points: hemodialysis independence rates at 6 and 12 months,
      hemodialysis- and chemotherapy-related adverse events, and death. Results: Among
      98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range,
      61.2-75.3 years]; 45% women) were included in the modified intent-to-treat
      analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in
      the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional
      hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P =
      .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively
      (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12
      months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference,
      23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related
      adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the
      conventional hemodialysis group; chemotherapy-related serious adverse events, 39%
      vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died.
      Conclusions and Relevance: Among patients with myeloma cast nephropathy treated
      with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis
      compared with conventional hemodialysis did not result in a statistically
      significant difference in hemodialysis independence at 3 months. However, the
      study may have been underpowered to identify an early clinically important
      difference. Trial Registration: clinicaltrials.gov Identifier: NCT01208818.

PMID- 29209725
TI  - Moral Choices for Today's Physician.

PMID- 29209727
TI  - Sentence-Level Movements in Parkinson's Disease: Loud, Clear, and Slow Speech.
AB  - Purpose: To further understand the effect of Parkinson's disease (PD) on
      articulatory movements in speech and to expand our knowledge of therapeutic
      treatment strategies, this study examined movements of the jaw, tongue blade, and
      tongue dorsum during sentence production with respect to speech intelligibility
      and compared the effect of varying speaking styles on these articulatory
      movements. Method: Twenty-one speakers with PD and 20 healthy controls produced 3
      sentences under normal, loud, clear, and slow speaking conditions. Speech
      intelligibility was rated for each speaker. A 3-dimensional electromagnetic
      articulograph tracked movements of the articulators. Measures included
      articulatory working spaces, ranges along the first principal component, average
      speeds, and sentence durations. Results: Speakers with PD demonstrated
      significantly smaller jaw movements as well as shorter than normal sentence
      durations. Between-speaker variation in movement size of the jaw, tongue blade,
      and tongue dorsum was associated with speech intelligibility. Analysis of
      speaking conditions revealed similar patterns of change in movement measures
      across groups and articulators: larger than normal movement sizes and faster
      speeds for loud speech, increased movement sizes for clear speech, and larger
      than normal movement sizes and slower speeds for slow speech. Conclusions:
      Sentence-level measures of articulatory movements are sensitive to both disease
      related changes in PD and speaking-style manipulations.

PMID- 29209728
TI  - Conceptual Scoring and Classification Accuracy of Vocabulary Testing in Bilingual
      Children.
AB  - Purpose: This study examined the effects of single-language and conceptual
      scoring on the vocabulary performance of bilingual children with and without
      specific language impairment. We assessed classification accuracy across 3
      scoring methods. Method: Participants included Spanish-English bilingual children
      (N = 247) aged 5;1 (years;months) to 11;1 with and without specific language
      impairment. Children completed the English and bilingual versions of the
      Expressive One-Word Picture Vocabulary Test-Third Edition (Brownell, 2000a,
      2001). Six scores, 2 representing monolingual scores in English and Spanish and 4
      conceptual scores, were derived. The conceptual scores included within-test
      conceptual scores, which credited language responses in the other language during
      test administration, and across-test conceptual scores, which we compiled by
      examining responses across independent administrations of the test in each
      language. Results: Across-test conceptual scoring resulted in the highest scores
      and better overall classification, sensitivity, and specificity than within-test
      conceptual scoring. Both were superior to monolingual scoring; however, none of
      the methods achieved minimum standards of 80% accuracy in sensitivity and
      specificity. Conclusions: Results suggest that bilingual children are not always
      able to readily access their other language in confrontation naming tasks.
      Priming or inhibition may play a role in test performance. Across-test conceptual
      scoring yielded the highest classification accuracy but did not meet minimum
      standards.

PMID- 29209729
TI  - Percent Grammatical Responses as a General Outcome Measure: Initial Validity.
AB  - Purpose: This report investigated the validity of using percent grammatical
      responses (PGR) as a measure for assessing grammaticality. To establish construct
      validity, we computed the correlation of PGR with another measure of grammar
      skills and with an unrelated skill area. To establish concurrent validity for
      PGR, we computed the correlation of PGR with a previously validated measure of
      grammaticality, percent grammatical utterances (PGU), and examined the extent to
      which PGR and PGU agreed upon pass/fail decisions for children. Method:
      Participants included 79 3-year-olds from mostly middle socioeconomic status
      homes. Language samples were elicited by asking children to describe 15 pictures
      in response to 4 questions per picture. To calculate PGU, children's responses to
      all 4 questions were segmented into communication units, and each communication
      unit was evaluated for grammatical errors. To calculate PGR, the entire response
      to just the first question was evaluated for grammatical errors. Results: PGR
      scores significantly correlated with a standardized test of grammar (r = .70),
      but not with a measure of vocabulary (i.e., type-token ratio; r = .11). In
      addition, PGR scores were significantly correlated with PGU scores (r = .88).
      Agreement between PGR and PGU was 92% for pass decisions and 94% for fail
      decisions. Conclusions: The current study establishes the construct validity of
      PGR as a measure of grammar and supports the use of PGR as a measure to assess
      grammaticality.

PMID- 29209730
TI  - Enhanced Identification of Long Versus Short Voice Onset Time Consonant-Vowel
      Syllables in a Dichotic Listening Task.
AB  - Purpose: This study investigated the influence of voice onset time (VOT) on the
      perception of consonant-vowel (CV) signals during a dichotic listening (DL) task.
      Method: Sixty-two young adults with normal hearing were tested with the English
      language version of the Hugdahl Dichotic CV (DCV) Test. They were asked to
      identify 1 CV syllable during 3 DL conditions: free recall (report the syllable
      heard most clearly), forced right (report the syllable in the right ear), and
      forced left (report the syllable in the left ear). Averages for number and
      percent correct syllables were recorded under each condition and across the
      entire test. Results: All subjects demonstrated an overall right-ear advantage
      (REA) when scores from all 3 listening conditions were averaged. The REA occurred
      for all VOT pairings except when the long VOT was presented to the left ear,
      whereas the short VOT was presented to the right ear when subjects produced an
      average left-ear advantage. The left-ear advantage overcame the structural
      advantage of the right ear even when subjects were directed to attend to the
      right ear. This result was consistent with findings of earlier studies done with
      Norwegian and Australian subjects. Conclusions: Listeners' REA may be overcome by
      interaural temporal differences that favor processing in the listener's
      nondominant ear during the DCV test. Balanced VOT conditions across the DCV test
      prevent this effect from producing an overall bias toward the left ear, but
      clinical DL tests with consonant-vowel-consonant words should be examined for
      effects of the long VOT on laterality of performance.

PMID- 29209731
TI  - Kinaesthetic ability training improves unilateral neglect and functional outcome
      in patients with stroke: A randomized control trial.
AB  - OBJECTIVE: To investigate the effects of kinaesthetic ability training with the
      Kinesthetic Ability Trainer (KAT) on unilateral neglect and functional outcomes
      in stroke patients. STUDY DESIGN: An assessor-blinded, randomized controlled,
      clinical trial. METHODS: A total of 64 stroke patients with unilateral neglect
      (mean age 61 (standard deviation (SD) 12) years, 60.4% male, mean time since
      stroke 6.4 (SD 10.4) months, left hemiplegia 92.5%) were randomly assigned to a
      conventional rehabilitation programme (control group, n = 32) or KAT plus a
      conventional rehabilitation programme (KAT group, n = 32) for 4 weeks. Patients
      were assessed with the Behavioral Inattention Test (BIT) and Functional
      Independence Measure (FIM) before and after therapy. RESULTS: Both groups showed
      significant improvements in all subscales of the BIT (conventional and
      behavioural) (p < 0.001) and the FIM motor scale (p < 0.001) after therapy.
      Recovery from neglect was assessed, based on the BIT cut-off scores. The recovery
      rate for behavioural BIT was 40% in the KAT group and 17.9% in the control group
      (p = 0.07), whereas recovery rates according to the conventional BIT were 16% and
      10.7% in the KAT and control groups, respectively. CONCLUSION: Kinaesthetic
      ability training provides clinically meaningful improvement in stroke patients
      with unilateral neglect. It may be useful as an adjunctive therapy for
      rehabilitation in these patients.

PMID- 29209732
TI  - Identification and fine mapping of a stay-green gene (Brnye1) in pakchoi
      (Brassica campestris L. ssp. chinensis).
AB  - KEY MESSAGE: Using bulked segregant analysis combined with next-generation
      sequencing, we delimited the Brnye1 gene responsible for the stay-green trait of
      nye in pakchoi. Sequence analysis identified Bra019346 as the candidate gene.
      "Stay-green" refers to a plant trait whereby leaves remain green during
      senescence. This trait is useful in the cultivation of pakchoi (Brassica
      campestris L. ssp. chinensis), which is marketed as a green leaf product. This
      study aimed to identify the gene responsible for the stay-green trait in pakchoi.
      We identified a stay-green mutant in pakchoi, which we termed "nye". Genetic
      analysis revealed that the stay-green trait is controlled by a single recessive
      gene, Brnye1. Using the BSA-seq method, a 3.0-Mb candidate region was mapped on
      chromosome A03, which helped us localize Brnye1 to an 81.01-kb interval between
      SSR markers SSRWN27 and SSRWN30 via linkage analysis in an F2 population. We
      identified 12 genes in this region, 11 of which were annotated based on the
      Brassica rapa annotation database, and one was a functionally unknown gene. An
      orthologous gene of the Arabidopsis gene AtNYE1, Bra019346, was identified as the
      potential candidate for Brnye1. Sequence analysis revealed a 40-bp insertion in
      the second exon of Bra019346 in nye, which generated the TAA stop codon. A
      candidate gene-specific Indel marker in 1561 F2 individuals showed perfect
      cosegregation with Brnye1 in the nye mutant. These results provide a foundation
      for uncovering the molecular mechanism of the stay-green trait in pakchoi.

PMID- 29209733
TI  - Quality of Surgery in Malawi: Comparison of Patient-Reported Outcomes After
      Hernia Surgery Between District and Central Hospitals.
AB  - BACKGROUND: District hospitals in Africa could meet the essential surgical needs
      of rural populations. However, evidence on outcomes is needed to justify
      investment in this option, given that surgery at district hospitals in some
      African countries is usually undertaken by non-physician clinicians. METHODS:
      Baseline and 2-3-month follow-up measurements were undertaken on 98 patients who
      had undergone hernia repairs at four district and two central hospitals in
      Malawi, using a modified quality-of-life tool. RESULTS: There was no significant
      difference in outcomes between district and central hospital cases, where a good
      outcome was defined as no more than one severe and three mild symptoms. Outcomes
      were marginally inferior at district hospitals (OR 0.79, 95% CI 0.63-1.0).
      However, in the 46 cases that underwent elective surgery at district hospitals,
      baseline scores for severe symptoms were worse (mean = 3.5) than in the 23
      elective central hospital cases (mean = 2.5), p = 0.004. Also, the mean change
      (improvement) in symptom score was higher in district versus central hospital
      cases (3.9 vs. 2.3). CONCLUSION: The study results support the case for investing
      in district hospital surgery in sub-Saharan Africa to increase access to
      essential surgical care for rural populations. This could free up specialists to
      undertake more complex and referred cases and reduce emergency presentations. It
      will require investments in training and resources for district hospitals and in
      supervision from higher levels.

PMID- 29209734
TI  - Effects of hypothyroidism on serotonin 1A receptors in the rat brain.
AB  - PURPOSE: We investigated the effects of hypothyroidism on serotonin 1A receptors
      in the rat brain in vivo. METHODS: Five surgically thyroidectomized male Sprague
      Dawley (SD) rats and five hypophysectomized SD rats were used as animal models of
      hypothyroidism; the same number of sham-operated SD rats served as age-matched
      controls. After hypothyroidism was confirmed by thyroid function tests, serotonin
      positron emission tomography (PET) was performed for 120 min. All PET data were
      spatially normalized to T2-weighted magnetic resonance imaging templates; then,
      time-activity curves of the hippocampus, septum, and cerebellum were extracted
      using predefined volume-of-interest templates. Non-displaceable binding values in
      the hippocampus and septum were calculated using a multilinear reference tissue
      model and parametric maps were constructed. Both volume-of-interest and voxel
      based analyses showed higher brain uptake in the thyroidectomized and
      hypophysectomized rats compared to the respective sham-operated rats. RESULTS:
      Time-activity curves showed that the brain uptake values for the thyroidectomized
      and hypophysectomized groups were 21-52% higher than were those in the respective
      control groups. In the thyroidectomized group, the binding potential values for
      the hippocampus and septum were 20-26% higher than were those in the sham
      thyroidectomized group. In the hypophysectomized group, the binding value for the
      hippocampus was 23% higher than was that in the sham-hypophysectomized group,
      whereas the septal binding was not significantly different from that in the sham
      hypophysectomized group. Parametric maps for the hypothyroidism also showed
      significantly higher binding values than did those for the controls. CONCLUSION:
      Our results demonstrate that hypothyroidism elevates serotonin 1A receptor
      binding in the limbic system.

PMID- 29209735
TI  - Atypical lipomatous tumor of the hand with transformation to dedifferentiated
      liposarcoma: a case report.
AB  - Atypical lipomatous tumor/well-differentiated liposarcoma is the most common
      sarcoma of soft tissue in adults. We describe the clinical, radiologic, and
      pathologic features of an atypical lipomatous tumor arising within the soft
      tissue of the left hand of a 68-year-old female that underwent transformation to
      dedifferentiated liposarcoma and eventually metastasized. At initial
      presentation, imaging demonstrated an extensively calcified fatty soft tissue
      mass with displacement of the digits. Following biopsy and staged debulking, the
      patient subsequently developed local recurrence, dedifferentiation, and
      widespread metastases to the lungs, pancreas, bone, and soft tissues. To our
      knowledge, this is the first case of a cytogenetically proven atypical lipomatous
      tumor of the hand that has undergone dedifferentiation with widespread
      metastases.

PMID- 29209736
TI  - Magnetic resonance imaging-based morphological and alignment assessment of the
      patellofemoral joint and its relationship to proximal patellar tendinopathy.
AB  - OBJECTIVE: To assess the differences in morphology and alignment of the knee
      between patients with proximal patellar tendinopathy (PPT) and a control group,
      using MRI and focusing on the patellofemoral joint. METHODS: We retrospectively
      included 35 patients with clinically diagnosed and unequivocal findings of PPT on
      knee MRI, the case group. For the control group, we included 70 patients who
      underwent knee MRI for other reasons, with no clinical or MRI evidence of PPT.
      Patients and controls were matched for age and gender, with all subjects
      reporting frequent physical activity. MRIs were evaluated by two musculoskeletal
      radiologists, who assessed parameters of patellar morphology, trochlear
      morphology, patellofemoral alignment, and tibiofemoral alignment. The differences
      in parameters between cases and controls were assessed using Student's t test.
      Logistic regression was applied to assess the associations between the MRI
      parameters and the presence of PPT. RESULTS: The patellar height Insall-Salvati
      ratio was different between cases and controls (1.37 +/- 0.21 vs. 1.24 +/- 0.19;
      p = 0.003). The subchondral Wiberg angle was higher in cases than controls (136.8
      +/- 7.4 vs. 131.7 +/- 8.8; p = 0.004). After applying logistic regression,
      significant associations with PPT were found [odds ratios (95% CI)] for patellar
      morphology [1.1 (1.0, 1.2)] and patellar height [1.3 (1.0, 1.7)]. CONCLUSIONS:
      Patellar height and the subchondral patellar Wiberg angle were greater in
      patients with PPT and significantly associated with PPT.

PMID- 29209737
TI  - Early mobilization of patients with non-operative liver and spleen injuries is
      safe and cost effective.
AB  - PURPOSE: There is no standard protocol for the management of non-operative liver
      or spleen injuries (LSI). In 2011, our institution changed the non-operative
      management (NOM) protocol of LSI from prolonged bed rest (PBR) to early
      mobilization (EM). We aim to show that EM safely decreases length of stay (LOS),
      ICU LOS, and cost. METHODS: We conducted a retrospective review in which non
      operative LSI patients observed PBR from January 2008 through July 2011 and were
      mobilized early from August 2011 through December 2014. Endpoints assessed were
      length of bed rest, hospital LOS, ICU LOS, failure of NOM, cost,
      angiography/embolization, and mortality. RESULTS: There were a total of 184
      patients with LSI who met study criteria and were not excluded. 77 patients
      utilized PBR between 2008 and 2011 and 107 followed EM protocol between 2011 and
      2014. There was no significant difference in the male to female ratio, age, ISS,
      anticoagulant use, or MOI. Both groups had similar injury profiles. PBR included
      34 liver injuries, 45 splenic injuries and two patients with both. EM included 63
      liver injuries, 55 splenic injuries and 11 patients with both (for liver injury p
      = 0.053, for splenic injury p = 0.37, and for combined p = 0.08). LOS and cost
      were significantly decreased in the EM cohort. LOS was shortened by 1.07 days (p
      = 0.005) and cost of hospitalization was reduced by $7077 (p = 0.046). There was
      no difference in NOM failure, angiography/embolization, or mortality. CONCLUSION:
      EM in non-operative LSI is safe and cost-effective. It results in decreased LOS
      and cost without increasing failure of NOM, angiography, embolization, or
      mortality.

PMID- 29209738
TI  - The Impact of Di(2-ethylhexyl)phthalate on Cancer Progression.
AB  - Di(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, mainly serves as an
      additive to render polyvinyl chloride (PVC) soft and flexible. PVC plastics have
      become ubiquitous in our modern society. Yet, the leaching of DEHP from PVC-based
      consumables ultimately results in the deposition in certain tissues via
      inadvertent applications. Health risks for human populations exposed to DEHP has
      been assumed by studies on rodents and other species, including the DEHP-induced
      developmental dysregulation, reproductive impairments, tumorigenesis, and
      diseases in a transgenerational manner. In this review, we comprehensively
      summarize the accumulated literature regarding the multifaceted roles of DEHP in
      the activation of the nuclear receptors, the alteration of the redox homeostasis,
      epigenetic modifications and the acquisition of chemoresistance.

PMID- 29209739
TI  - Hepatocarcinogenesis and LI-RADS.
AB  - Hepatocarcinogenesis is a multi-step process characterized by progressive
      cellular and molecular dedifferentiation of hepatocytes and culminating in the
      emergence of hepatocellular carcinoma (HCC). Knowledge of hepatocarcinogenesis is
      important because familiarity with the associated imaging features can lead to
      improved diagnosis of HCC at its early stages. The article reviews the
      alterations that accumulate leading to HCC result in abnormal imaging features,
      many of which are included in LI-RADS v2017 as major and ancillary features.

PMID- 29209740
TI  - Early deficits in insulin secretion, beta cell mass and islet blood perfusion
      precede onset of autoimmune type 1 diabetes in BioBreeding rats.
AB  - AIMS/HYPOTHESIS: Genetic studies show coupling of genes affecting beta cell
      function to type 1 diabetes, but hitherto no studies on whether beta cell
      dysfunction could precede insulitis and clinical onset of type 1 diabetes are
      available. METHODS: We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model
      of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and
      DR+/+ littermates (controls) to investigate beta cell function in vivo, and
      insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical
      projection tomography (OPT) and morphometry. Additionally, measurements of intra
      islet blood flow were performed using microsphere injections. We also assessed
      immune cell infiltration, cytokine expression in islets (by immunohistochemistry
      and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine
      effects on glucose uptake and metabolism in beta cells. RESULTS: DRLyp/Lyp rats
      were normoglycaemic and without traces of immune cell infiltrates. However,
      IVGTTs revealed a significant decrease in the acute insulin response to glucose
      compared with control rats (1685.3 +/- 121.3 vs 633.3 +/- 148.7; p < 0.0001). In
      agreement, insulin secretion was severely perturbed in isolated islets, and both
      first- and second-phase insulin release were lowered compared with control rats,
      while glucagon secretion was similar in both groups. Interestingly, after 5-7
      days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated
      insulin secretion (GSIS) was improved; although, a significant decrease in GSIS
      was still evident compared with islets from control rats at this time (7393.9 +/-
      1593.7 vs 4416.8 +/- 1230.5 pg islet-1 h-1; p < 0.0001). Compared with controls,
      OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in
      medium (4.1 * 109 +/- 9.5 * 107 vs 3.8 * 109 +/- 5.8 * 107 MUm3; p = 0.044) and
      small sized islets (1.6 * 109 +/- 5.1 * 107 vs 1.4 * 109 +/- 4.5 * 107 MUm3; p =
      0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1 +/-
      16.8 vs 76.9 +/- 11.8 MUl min-1 [g pancreas]-1; p = 0.023) and alterations in the
      beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats.
      CONCLUSIONS/INTERPRETATION: The present study identifies a deterioration of beta
      cell function and mass, and intra-islet blood flow that precedes insulitis and
      diabetes development in animals prone to autoimmune type 1 diabetes. These
      underlying changes in islet function may be previously unrecognised factors of
      importance in type 1 diabetes development.

PMID- 29209741
TI  - Total elbow arthroplasty under unfavourable soft tissue conditions.
AB  - PURPOSE: To evaluate the clinical and radiographic outcomes of patients with
      total elbow arthroplasty (TEA) and soft tissue reconstruction. METHODS: We
      investigated six patients who underwent TEA and soft tissue reconstruction (two
      elbows with 1-stage surgery and four elbows with 2-stage surgery). The mean
      patient age at the time of the surgical procedure was 43.2 years; the mean follow
      up duration was 88.2 months. RESULTS: The mean pain visual analogue scale (VAS)
      during motion was improved from 6.3 pre-operatively to 0.7 at the last follow-up.
      The mean Mayo Elbow Performance Score (MEPS) improved from 26.7 pre-operatively
      to 81.7 at the last follow-up. The mean flexion-extension arcs of the 1- and 2
      stage surgery groups increased from 12.5 degrees  and 13.8 degrees  pre
      operatively to 72.5 degrees  and 100 degrees  at the last follow-up,
      respectively. The mean MEPS of the one and two stage surgery groups were 75 and
      85, respectively, at the last follow-up. One of the six elbows had loosening on
      the simple radiograph at the last follow-up, and there were no cases with bushing
      wear. Three elbows needed additional skin debridement owing to wound
      complications (2/2 elbows in the 1-stage surgery group and 1/4 elbows in the 2
      stage surgery group). CONCLUSIONS: Under unfavorable soft tissue conditions,
      performing soft tissue reconstruction with TEA provides satisfactory functional
      improvement and pain relief. The two stage surgery provided a lower rate of wound
      complication and better elbow function than the one stage surgery, which led to
      high patient satisfaction post-operatively. LEVEL OF EVIDENCE: Therapeutic Level
      IV.

PMID- 29209742
TI  - The prevalence and risk factors for delayed union of the superior pubic ramus at
      one year after curved periacetabular osteotomy: its risk factor and outcome.
AB  - PURPOSE: Curved periacetabular osteotomy (CPO) has been developed for the
      treatment of acetabular dysplasia. While several studies have reported its good
      clinical results, the complications of CPO include delayed union and nonunion of
      the superior pubic ramus. The purpose of this study is to investigate the
      prevalence of delayed union of the pubis one year after CPO, and to determine the
      risk factors for this complication. METHODS: The study examined 113 hips that
      underwent CPO between 2008 and 2012. Delayed union was assessed based on the
      anteroposterior radiography one year after CPO. A superior pubic ramus union
      group (U group) and a delayed union group (D group) were retrospectively compared
      regarding patient characteristics, clinical evaluations, and radiographic
      parameters. RESULTS: Delayed union rate was 16.8%. The D group contained a
      significantly greater proportion of smokers (p < 0.001). The gap at the pubic
      osteotomy site on CT coronal images was significantly larger in the D group (p <
      0.001), and the cut-off value for the risk of nonunion was larger than 5.1 mm.
      Multivariate regression analysis indicated that smoking (OR 10.7, 95% CI 2.1
      55.4) and a gap at the superior pubic ramus >5.1 mm (OR 16.5, 95% CI 3.7-73.7)
      were significantly associated with delayed union as independent risk factors.
      CONCLUSION: The prevalence of delayed union one year after CPO was 16.8%. Smoking
      and a gap larger than 5.1 mm at the pubic osteotomy site are risk factors for
      delayed union after CPO.

PMID- 29209744
TI  - Preserved Myocardial Deformation after Successful Coarctation Repair: A CMR
      Feature-Tracking Study.
AB  - Arterial vasculopathy and residual aortic obstruction can lead to left
      ventricular (LV) dysfunction in patients with coarctation of the aorta (CoA)
      related to adverse ventriculo-arterial coupling. This study aimed to investigate
      potential differences in LV myocardial deformation indices between repaired CoA
      patients and healthy controls. Twenty-two CoA patients (age 30 +/- 10.6 years)
      after surgical repair (n = 12) or balloon angioplasty (BA) (n = 10) without
      residual stenosis, between 3 months and 16 years of age with > 10 years follow-up
      were compared to 22 healthy age- and gender-matched controls (age 30 +/- 3.8
      years). Cardiac magnetic resonance feature tracking (CMR-FT) was used for LV
      longitudinal-, circumferential-, and rotational deformation indices. Global
      systolic LV function was preserved in CoA patients (LV ejection fraction 58 +/-
      4.8 vs. 60 +/- 6.8%, p = 0.56) when compared to controls, with normal LV
      dimensions and mass (p > 0.05). Twelve CoA patients (55%) were hypertensive, of
      whom 4 were on anti-hypertensive medication. LV global longitudinal strain was
      preserved in the four-chamber (- 18 +/- 4.4 vs. - 16 +/- 4.7%, p = 0.06) and two
      chamber (- 22 +/- 5.1 vs. - 20 +/- 6.0%, p = 0.22) orientations in CoA patients.
      Global circumferential strain was preserved at basal (- 29 +/- 4.1 vs. - 28 +/-
      4.8%, p = 0.43), mid-ventricular (- 27 +/- 4.2 vs. - 25 +/- 3.0%, p = 0.09), and
      apical levels (- 35 +/- 7.8 vs. - 32 +/- 34.9%, p = 0.32). No differences were
      found in global torsion (2.4 +/- 1.3 degrees  vs. 2.0 +/- 1.4 degrees /cm, p =
      0.28), twist (14 +/- 5.8 degrees  vs. 12 +/- 6.3 degrees , p = 0.34), and recoil
      rate (- 17 +/- 9.7 degrees  vs. - 17 +/- 7.1 degrees /cm s, p = 0.97). Analysis
      of intra-observer variability demonstrated good reproducibility for all CMR
      deformation indices. Global and rotational myocardial deformation indices are
      preserved in CoA patients long-term after repair without residual stenosis,
      despite a high incidence of hypertension.

PMID- 29209745
TI  - Trends and socio-economic determinants of suicide in India: 2001-2013.
AB  - PURPOSE: To investigate trends and socio-economic determinants of suicide in
      India over the period of 2001-2013. METHOD: Suicide rates between 2001 and 2013
      were calculated using suicide statistics provided by National Crime Records
      Bureau (NCRB) and census data provided by Census of India, stratified by sex, age
      group, and geographical region, to investigate trends in suicide over the study
      period. Multilevel negative binomial regression models were specified to
      investigate associations between state-level indicators of economic development,
      education, employment and religious factors and sex-specific suicide rates.
      RESULTS: Male suicide rates remained relatively steady (~ 14 per 100,000) while
      female suicide rates decreased over the study period (9 to 7 per 100,000). The
      age group of 45-59 years had the highest suicide rate among males while the age
      group of 15-29 years had the highest suicide rate among females. On average,
      higher male and female suicide rates were observed in states with: higher levels
      of development, higher levels of agricultural employment, higher levels of
      literacy, and higher proportions of people identifying with Hinduism. Higher male
      suicide rates were also observed in states with higher levels of unemployment.
      CONCLUSION: The process of modernization might be contributing towards higher
      suicide risk in more developed parts of India. Also, increase in farmer suicides
      since economic liberalization might be contributing towards higher suicide rates
      among more agricultural regions. Furthermore, ancient sanctions towards religious
      suicide are possibly still influencing modern Hindu suicides.

PMID- 29209743
TI  - Gastroprotective activity of the methanol extract from peels of Plinia edulis
      (Vell.) Sobral fruits and its isolated triterpenes: maslinic and ursolic acids.
AB  - According to the Brazilian folk medicine, the leaves of Plinia edulis (Vell.)
      Sobral (Myrtaceae), known as cambuca, are indicated in the treatment of gastric
      disorders. Infusions of P. edulis leaves were previously demonstrated to contain
      both maslinic (MA) and ursolic acids (UA). Both triterpenes have also been
      identified in the methanolic extract of peels from P. edulis fruit (MEPPE);
      however, the antiulcer effects of MEPPE have not yet been studied. This study
      therefore evaluates the gastroprotective potential of MEPPE, MA, and UA using
      ethanol/HCl- and indomethacin-induced gastric ulcers in mice. In addition, the in
      vitro effects of these compounds on the H+, K+-ATPase activity and on the free
      radical DPPH were measured. When used at concentration of 100 MUg/mL, both MEPPE
      and UA were found to reduce the DPPH radical levels by 78.66 and 60.14%,
      respectively. However, MA did not reduce DPPH radical levels. Our results
      illustrated the antiulcer effects of MEPPE, MA, and UA against experimental ulcer
      models when administered by either the oral or the intraperitoneal routes. In
      addition, MEPPE reduced the size of ethanol/HCl-induced ulcers in a dose
      dependent manner (log half-maximal effective oral dose, LogED50 = 1.09).
      Interestingly, UA promoted gastroprotection at lower doses than MA by increasing
      the production of mucin levels at 692%; however, it does not alter the activity
      of H+, K+-ATPase. In contrast, both MEPPE and MA, when incubated at
      concentrations of 10 and 100 MUg/mL, inhibited H+, K+-ATPase activity in 61.81,
      68.37, 54.04, and 70.45%, respectively. These results confirm that MEPPE, MA, and
      UA display gastroprotective activity through different modes of action; MA
      inhibits H+, K+-ATPase activity, whereas UA favour the mucus barrier.

PMID- 29209746
TI  - Decisional conflict in mental health care: a cross-sectional study.
AB  - PURPOSE: Decisional conflict refers to the degree to which patients are engaged
      in and feel comfortable about important clinical decisions. Until now, the
      concept has received little attention in mental health care. We investigate the
      level of decisional conflict in mental health care and whether this is influenced
      by socio-demographics, treatment setting, diagnoses, and locus of control.
      METHODS: Cross-sectional study among 186 patients in Dutch specialist mental
      health care using the Decisional Conflict Scale, which measures five dimensions
      of decisional conflict: information, support, clarification of values, certainty,
      and decisional quality. Descriptive statistics and forward stepwise linear
      regression analyses were used. RESULTS: Patients report relatively high levels of
      decisional conflict, especially those with more external locus of control. Having
      a personality disorder and higher education also increases decisional conflict on
      the dimensions support and clarification of values, respectively. Less decisional
      conflict was experienced by patients with psychotic disorders on the dimension
      certainty and by women on the information domain. CONCLUSIONS: Decisional
      conflict is common among patients in specialist mental health care and is very
      useful for assessing the quality of clinical decision making. Measuring
      decisional conflict and knowledge about influencing factors can be used to
      improve patients' participation in clinical decision making, adherence to
      treatment and clinical outcomes.

PMID- 29209748
TI  - Monitoring cytochrome P450 activity in living hepatocytes by chromogenic
      substrates in response to drug treatment or during cell maturation.
AB  - The metabolic activity of hepatocytes is a central prerequisite for drug activity
      and a key element in drug-drug interaction. This central role in metabolism
      largely depends on the activity of the cytochrome P450 (CYP450) enzyme family,
      which is not only dependent on liver cell maturation but is also controlled in
      response to drug and chemical exposure. Here, we report the use of VividDye
      fluorogenic CYP450 substrates to directly measure and continuously monitor
      metabolic activity in living hepatocytes. We observed time- and dose-dependent
      correlation in response to established and putative CYP450 inducers acting
      through the aryl hydrocarbon receptor and drug combinations. Using repetitive
      addition of VividDye fluorogenic substrate on a daily basis, we demonstrated the
      new application of VividDye for monitoring the maturation and dedifferentiation
      of hepatic cells. Despite a lack of high specificity for individual CYP450
      isoenzymes, our approach enables continuous monitoring of metabolic activity in
      living cells with no need to disrupt cultivation. Our assay can be integrated in
      in vitro liver-mimetic models for on-line monitoring and thus should enhance the
      reliability of these tissue model systems.

PMID- 29209750
TI  - Founder of EJNM passed away.

PMID- 29209751
TI  - [Specific components for integrative and flexible care models according to S 64b
      SGB V].
AB  - BACKGROUND: There is a need for a theoretical model for evaluating integrative
      and flexible care models according to S 64b of the Social Security Statutes Book
      V (SGB V). MATERIAL AND METHODS: An iterative process of data collection and
      analysis has been executed according to grounded theory methodology. RESULTS: A
      total of 11 specific components have been identified and shown to be robust and
      practicable and compatible with the data from the literature. CONCLUSION: These
      components can be used for implementation, quality management and evaluation of
      projects for treatment models according to S 64b SGB V.

PMID- 29209749
TI  - [Quality indicators for metabolic and bariatric surgery in Germany : Evidence
      based development of an indicator panel for the quality of results, indications
      and structure].
AB  - An expert committee was appointed by the German Society for General and Visceral
      Surgery to develop a panel of appropriate quality indicators to collate the
      quality of results, indications and structure in metabolic and bariatric surgery.
      This entailed assimilating the available evidence (systematic literature search),
      results from the national registry of the society (StuDoQ|MBE) and specific
      socioeconomic aspects (e. g. severely limited access to metabolic and bariatric
      surgery in Germany). These quality parameters were to be incorporated into the
      national guidelines and the rules of procedure for certification in the future.
      The committee concluded that mortality, MTL30 and severe complications needing
      intervention (Clavien-Dindo >= 3b) are suitable indicators to measure surgical
      outcome quality due to their relevance, scientific soundness and practicability.
      As a systematic follow-up is mandatory after bariatric surgery, a minimum follow
      up quota is now required using reported quality of life data as an indicator of
      process quality. As intestinal bypass procedures have been shown to be superior
      in the treatment of type 2 diabetes, these procedures should be offered to
      eligible patients and also be performed. The proposed threshold values based on
      the results of the available literature and StuDoQ registry are to be considered
      as preliminary and need to be validated and adjusted if necessary in the future.
      The StuDoQ|MBE is considered a valuable tool to gather this information and also
      represents the appropriate infrastructure for the collation of relevant risk
      adjustors.

PMID- 29209752
TI  - [Addiction as an attachment disorder].
AB  - BACKGROUND: There is no commonly accepted model for describing the development
      and treatment of substance use disorders (SUD); however, over several decades the
      attachment theory has represented an important basis for the clinical handling of
      SUD. This study gives a systematic review of empirical studies regarding the
      relationship between SUD and disorders of attachment behavior. OBJECTIVE: Is
      there a positive relationship between disorders of attachment behavior and the
      presence of SUD? METHOD: Various databases (PsychInfo, Web of Science, PubMed)
      were systematically searched in order to pinpoint relevant studies in books and
      articles published in English or German. Based on the results 22 publications
      were selected. After a stricter limitation to original research, 12 articles
      could finally be accepted as eligible. RESULTS: A significant relationship was
      found between SUD and insecure attachment in 10 out of the 12 studies.
      CONCLUSION: Based on the results of the research studies reviewed the hypothesis
      to characterize SUD as a possible expression of an attachment disorder was
      confirmed. This corroborates the importance of considering attachment parameters
      in dealing with prevention and treatment of SUD. Further research might focus on
      non-substance-related addictive disorders and therapy outcome studies.

PMID- 29209753
TI  - [Neuroleptic malignant syndrome].
AB  - BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare but severe undesired
      complication of psychopharmacological treatment. The mortality has shown a
      significant decrease since its first description. Knowledge of NMS is important
      for every clinician because of the need for rapid diagnosis and treatment.
      OBJECTIVE: This article presents a review and critical appraisal of the current
      study situation for NMS. Recommendations for diagnostics, differential
      diagnostics and treatment are presented particularly from a clinical perspective.
      MATERIAL AND METHODS: A literature review with the keywords "neuroleptic
      malignant syndrome", "Malignes neuroleptisches Syndrom" and various psychotropic
      drugs was performed in PubMed. The database of the Working Group for
      Pharmaceutical Treatment of Psychiatric Diseases (Arbeitsgemeinschaft fur
      Arzneimitteltherapie bei psychiatrischen Erkrankungen, AGATE) was analyzed with
      respect to registered cases of the undesired side effect NMS. RESULTS: In
      contrast to the first description, which also led to the name, there are now case
      reports of clinical conditions similar to NMS, which were obviously triggered by
      several groups of psychotropic drugs not just antipsychotic agents (German:
      Neuroleptika). Treatment recommendations exist whereby the effectiveness cannot
      always be scientifically substantiated; however, it is still undisputed that a
      rapid initiation of treatment is of great importance. DISCUSSION: The
      psychiatrist must be familiar with the symptoms of NMS, its differential
      diagnosis and the therapeutic options for a rapid and effective treatment.
      Further studies are urgently needed for scientific substantiation of the
      pathophysiology of NMS and to develop evidence-based guidelines for treatment.

PMID- 29209754
TI  - [Stricture of the vesicourethral anastomosis after radical prostatectomy].
AB  - BACKGROUND: The development of a stricture of the vesicourethral anastomosis is a
      serious complication after radical prostatectomy. Strictures occur in 5-8% of
      patients after radical prostatectomy. SYMPTOMS: Usually the clinical symptoms
      include an irritative and obstructive component similar to benign prostatic
      hyperplasia. In rare cases, patients suffer from partial or complete stress
      incontinence as a result of the anastomotic stricture. DIAGNOSTICS: The
      diagnostic workup is similar to the procedure for urethral strictures. In
      addition to uroflowmetry, a cystourethrogram (CUG) or, if necessary, a
      micturating cystourethrogram (MCU) can be performed. A urethrocystoscopy can be
      performed to ensure the diagnosis. THERAPY: In most cases, endoscopic procedures
      were performed for treatment. Beside a transurethral dilation of the stricture or
      the Sachse urethrotomy, the most common procedure is transurethral resection to
      treat the stricture. However, all procedures are associated with a high
      recurrence rate. In recurrent strictures, open surgical procedures, usually a
      perineal reanastomosis, should performed early. CONCLUSION: Endourological
      procedures like transurethral resection are a good treatment option, but due to
      the high recurrence rates, open surgical procedures should be discussed and if
      necessary should be performed early.

PMID- 29209756
TI  - Correction to: Treatment of Osteoid Osteomas Using a Navigational Bipolar
      Radiofrequency Ablation System.
AB  - In "Radiofrequency Ablation Procedure" section of the original article, the
      relationship between the location of the thermocouples and the size of the
      ablation zones is inaccurate and not consistent with the referenced article in
      the bibliography (#3. Hillen et al).

PMID- 29209755
TI  - [Evaluation of a prostate cancer E-health tutorial : Development and testing of
      the website prostata-information.ch].
AB  - BACKGROUND: Due to the multitude of therapy options, the treatment decision after
      diagnosis of localized prostate cancer is challenging. Compared to printed
      booklets, web-based information technology offers more possibilities to tailor
      information to patients' individual needs. OBJECTIVES: To support the decision
      making process as well as the communication with patients, we developed an online
      tutorial in a systematic process in the German-speaking part of Switzerland and
      then tested it in a pilot study. The study investigated users' satisfaction, the
      coverage of information needs, the preparation for decision making, and the
      subjective quality of the decision. MATERIALS AND METHODS: Based on already
      existing information material, the online tutorial was developed in an iterative
      process using focus groups with patients and urologists. For the following
      evaluation in eight clinics a total of 87 patients were invited to access the
      platform and participate in the study. Of these patients, 56 used the tutorial
      and 48 answered both surveys (the first one 4 weeks after the first login and the
      second one 3 months after treatment decision). The surveys used the Preparation
      for Decision Making Scale (PDMS), the Decisional Conflict Scale (DCS), and the
      Decisional Regret Scale (DRS). RESULTS AND CONCLUSION: Satisfaction with the
      tutorial is very high among patients with newly diagnosed localized prostate
      cancer. Users find their information needs sufficiently covered. Three months
      after the decision they felt that they were well prepared for the decision making
      (mean PDMS 75, standard deviation [SD] 23), they had low decisional conflict
      (mean DCS 9.6, SD 11), and almost no decisional regret (mean DRS 6.4, SD 9.6).
      Based on these findings, further use of the tutorial can be recommended.

PMID- 29209757
TI  - Eighth Edition of the UICC Classification of Malignant Tumours: an overview of
      the changes in the pathological TNM classification criteria-What has changed and
      why?
AB  - The TNM classification of malignant tumours is a mainstay tool in clinical
      practice and research for prognostic assessment of patients, treatment allocation
      and trial enrolment, as well as for epidemiological studies and data collection
      by cancer registries worldwide. Pathological TNM (pTNM) represents the
      pathological classification of a tumor, assigned after surgical resection or
      adequate sampling by biopsy, and periodical updates to the relative
      classification criteria are necessary to preserve its clinical relevance by
      integrating newly reported data. A structured approach has been put in place to
      fulfil this need and, based upon this process, the Eighth Edition of Union for
      International Cancer Control (UICC) TNM Classification of Malignant Tumours has
      been published, introducing many significant changes, including novel
      classification criteria for specific tumour types. In this review, we aim to
      describe the major changes introduced in the pTNM classification criteria and to
      summarize the evidence supporting these changes.

PMID- 29209759
TI  - [Private medical education in Germany].
AB  - Through the years, a range of privately funded medical training opportunities has
      been established in Germany. Only a few of them operate along the German Medical
      Licensure Act and thus underlie quality assurance regulations in Germany. Most of
      the courses are a result of German hospitals cooperating with universities from
      other EU countries. The content of the courses and the examinations underlie the
      regulations of the university's home country. This article aims to give an
      overview of the private medical training opportunities offered in Germany and to
      show differences compared to state funded German medical schools. The authors
      discuss the opportunities of private medical training as well as its challenges
      and risks. Basic principles concerning finances and quality assurance of national
      and international private medical training are provided. Regardless of their mode
      of financing, the superior goal of the training, according to the German Medical
      Licensure Act, should always be to enable young doctors to pursue further
      professional training, so that they can maintain the best possible quality in
      patient care, research, and medical education.

PMID- 29209758
TI  - Optimal literature search for systematic reviews in surgery.
AB  - BACKGROUND: The aim of the present study was to determine empirically which
      electronic databases contribute best to a literature search in surgical
      systematic reviews. METHODS: For ten published systematic reviews, the systematic
      literature searches were repeated in the databases MEDLINE, Web of Science,
      CENTRAL, and EMBASE. On the basis of these reviews, a gold standard set of
      eligible articles was created. Recall (%), precision (%), unique contribution
      (%), and numbers needed to read (NNR) were calculated for each database, as well
      as for searches of citing references and of the reference lists of related
      systematic reviews (hand search). RESULTS: CENTRAL yielded the highest recall
      (88.4%) and precision (8.3%) for randomized controlled trials (RCT), MEDLINE for
      non-randomized studies (NRS; recall 92.6%, precision 5.2%). The most effective
      combination of two databases plus hand searching for RCT was MEDLINE/CENTRAL
      (98.6% recall, NNR 97). Adding EMBASE marginally increased the recall to 99.3%,
      but with an NNR of 152. For NRS, the most effective combination was MEDLINE/Web
      of Science (99.5% recall, NNR 60). CONCLUSIONS: For surgical systematic reviews,
      the optimal literature search for RCT employs MEDLINE and CENTRAL. For surgical
      systematic reviews of NRS, Web of Science instead of CENTRAL should be searched.
      EMBASE does not contribute substantially to reviews with a surgical intervention.

PMID- 29209760
TI  - [60 years of Bundesgesundheitsblatt - a very personal laudatio].

PMID- 29209747
TI  - An adverse outcome pathway for parkinsonian motor deficits associated with
      mitochondrial complex I inhibition.
AB  - Epidemiological studies have observed an association between pesticide exposure
      and the development of Parkinson's disease, but have not established causality.
      The concept of an adverse outcome pathway (AOP) has been developed as a framework
      for the organization of available information linking the modulation of a
      molecular target [molecular initiating event (MIE)], via a sequence of essential
      biological key events (KEs), with an adverse outcome (AO). Here, we present an
      AOP covering the toxicological pathways that link the binding of an inhibitor to
      mitochondrial complex I (i.e., the MIE) with the onset of parkinsonian motor
      deficits (i.e., the AO). This AOP was developed according to the Organisation for
      Economic Co-operation and Development guidelines and uploaded to the AOP
      database. The KEs linking complex I inhibition to parkinsonian motor deficits are
      mitochondrial dysfunction, impaired proteostasis, neuroinflammation, and the
      degeneration of dopaminergic neurons of the substantia nigra. These KEs, by
      convention, were linearly organized. However, there was also evidence of
      additional feed-forward connections and shortcuts between the KEs, possibly
      depending on the intensity of the insult and the model system applied. The
      present AOP demonstrates mechanistic plausibility for epidemiological
      observations on a relationship between pesticide exposure and an elevated risk
      for Parkinson's disease development.

PMID- 29209761
TI  - [Shortage of physicians in rural areas and in the public health service : A
      critical analysis of the evidence on the role of medical education and training].
AB  - BACKGROUND: A shortage of medical personnel has been seen for several decades in
      at least two sectors of the healthcare system: primary care in remote areas as
      well as medical care in the state public health departments (Offentliches
      Gesundheitswesen). Strategies to reduce these problems are being sought.
      OBJECTIVE: This review examines the proposals, practical initiatives and
      empirical studies in under- and postgraduate medical education in order to
      estimate their potential impact on the solution of these problems. The analysis
      covers both Germany and Anglo-Saxon countries. MATERIALS AND METHODS: The study
      is based on a literature search in PubMed and Medline covering the last 20 years.
      With regard to Germany, programmatic documents and studies published in the
      German Journal of General Practice (Zeitschrift fur Allgemeinmedizin) were also
      included. RESULTS AND DISCUSSION: Foreign empirical studies identify almost equal
      two factors with regard to primary care in remote areas: the recruitment of
      students from rural areas combined with special educational programs with a rural
      primary care orientation both in under- and postgraduate medical education. These
      programs should include several and longer practical working periods in primary
      care units and be well coordinated between the medical school and the local
      teaching physicians. As for the state public health sector, comparable
      initiatives are still lacking.

PMID- 29209767
TI  - Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French
      cadaver-sourced growth hormone batches suggest possible transmission of tauopathy
      and long incubation periods for the transmission of Abeta pathology.
AB  - Abeta deposits and tau pathology were investigated in 24 French patients that
      died from iatrogenic Creutzfeldt-Jakob disease after exposure to cadaver-derived
      human growth hormone (c-hGH) in the 1980s. Abeta deposits were found only in one
      case that had experienced one of the longest incubation periods. Three cases had
      also intracellular tau accumulation. The analysis of 24 batches of c-hGH,
      produced between 1974 and 1988, demonstrated for the first time the presence of
      Abeta and tau contaminants in c-hGH (in 17 and 6 batches, respectively). The
      incubation of prion disease was shorter in the French patients than the
      incubation times reported in two previously published British series. We
      interpreted the low incidence of Abeta in this French series as a consequence of
      the shorter incubation period observed in France, as compared to that observed in
      the United Kingdom. This concept suggested that a mean incubation period for the
      development of detectable Abeta deposits would be longer than 18 years after the
      first exposure. Moreover, we hypothesized that tau pathology might also be
      transmissible in humans.

PMID- 29209768
TI  - Spread of aggregates after olfactory bulb injection of alpha-synuclein fibrils is
      associated with early neuronal loss and is reduced long term.
AB  - Parkinson's disease is characterized by degeneration of substantia nigra dopamine
      neurons and by intraneuronal aggregates, primarily composed of misfolded alpha
      synuclein. The alpha-synuclein aggregates in Parkinson's patients are suggested
      to first appear in the olfactory bulb and enteric nerves and then propagate,
      following a stereotypic pattern, via neural pathways to numerous regions across
      the brain. We recently demonstrated that after injection of either mouse or human
      alpha-synuclein fibrils into the olfactory bulb of wild-type mice, alpha
      synuclein fibrils recruited endogenous alpha-synuclein into pathological
      aggregates that spread transneuronally to over 40 other brain regions and
      subregions, over 12 months. We previously reported the progressive spreading of
      alpha-synuclein aggregates, between 1 and 12 months following alpha-synuclein
      fibril injections, and now report how far the pathology has spread 18- and 23
      month post-injection in this model. Our data show that between 12 and 18 months,
      there is a further increase in the number of brain regions exhibiting pathology
      after human, and to a lesser extent mouse, alpha-synuclein fibril injections. At
      both 18 and 23 months after injection of mouse and human alpha-synuclein fibrils,
      we observed a reduction in the density of alpha-synuclein aggregates in some
      brain regions compared to others at 12 months. At 23 months, no additional brain
      regions exhibited alpha-synuclein aggregates compared to earlier time points. In
      addition, we also demonstrate that the induced alpha-synucleinopathy triggered a
      significant early neuron loss in the anterior olfactory nucleus. By contrast,
      there was no loss of mitral neurons in the olfactory bulb, even at 18 month post
      injection. We speculate that the lack of continued progression of alpha-synuclein
      pathology is due to compromise of the neural circuitry, consequential to neuron
      loss and possibly to the activation of proteolytic mechanisms in resilient
      neurons of wild-type mice that counterbalances the spread and seeding by
      degrading pathogenic alpha-synuclein.

PMID- 29209769
TI  - Different behavioral, neural and neuropeptide responses of fathers to their own
      and to alien pups in mandarin voles.
AB  - Mothers often prefer to care for their own offspring rather than those of other
      females. However, whether fathers respond differently to their own pups and to
      alien ones remains unclear. In this study, we found that male mandarin voles
      (Microtus mandarinus) directed more sniffing toward their own pups than toward
      alien pups. The numbers of Fos-immunoreactive neurons in the medial preoptic
      nucleus, bed nucleus of the stria terminalis, nucleus accumbens, anterior
      cingulate cortex were significantly increased when fathers were exposed to an
      alien pups; however, more brain regions such as paraventricular nucleus,
      hypothalamic supraoptic nucleus, lateral habenula, ventral lateral septal
      nucleus, and medial amygdaloid nucleus showed increased number of Fos
      immunoreactive neurons activated when the fathers were exposed to their own pups.
      Exposure to their own pups also induced a greater number of Fos-immunoreactive
      neurons in the anterior cingulate cortex, paraventricular nucleus, hypothalamic
      supraoptic nucleus, lateral habenula, ventral lateral septal nucleus and medial
      amygdaloid nucleus, as well as higher expression of oxytocin and vasopressin in
      the paraventricular nucleus, compared with exposure to alien pups. Our results
      indicated that fathers demonstrated different behavioral and neural responses to
      their own and to alien pups.

PMID- 29209770
TI  - Androgen and estrogen sensitivity of bird song: a comparative view on gene
      regulatory levels.
AB  - Singing of songbirds is sensitive to testosterone and its androgenic and
      estrogenic metabolites in a species-specific way. The hormonal effects on song
      pattern are likely mediated by androgen receptors (AR) and estrogen receptor
      alpha (ERalpha), ligand activated transcription factors that are expressed in
      neurons of various areas of the songbirds' vocal control circuit. The
      distribution of AR in this circuit is rather similar between species while that
      of ERalpha is species variant and concerns a key vocal control area, the HVC
      (proper name). We discuss the regulation of the expression of the cognate AR and
      ERalpha and putative splice variants. In particular, we suggest that
      transcription factor binding sites in the promoter of these receptors differ
      between bird species. Further, we suggest that AR- and ERalpha-dependent gene
      regulation in vocal areas differs between species due to species-specific DNA
      binding sites of putative target genes that are required for the transcriptional
      activity of the receptors. We suggest that species differences in the
      distribution of AR and ERalpha in vocal areas and in the genomic sensitivity to
      these receptors contribute to species-specific hormonal regulation of the song.

PMID- 29209772
TI  - Influence of the ABCB1 polymorphisms on the response to Taxane-containing
      chemotherapy: a systematic review and meta-analysis.
AB  - PURPOSE: Multidrug resistance mediated by ABCB1 has been perceived to be one of
      the obstacles for cancer chemotherapy. This meta-analysis was performed to verify
      the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to
      Taxane-containing chemotherapy. METHODS: Pooled odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) were employed to evaluate the impact
      of these two ABCB1 polymorphisms. R scripts were developed to perform the meta
      analysis. RESULTS: A total of nine articles (including nine studies for rs1045642
      and five for rs1128503) were collected in our systematic review. However, our
      meta-analysis showed no significant effect of these two ABCB1 polymorphisms on
      the response to Taxane-containing regimens. CONCLUSIONS: This study highlights
      the unsuitability of relying on the ABCB1 rs1045642 and rs1128503 polymorphisms
      as therapeutic response biomarkers of Taxane-containing chemotherapy. Further
      polycentric studies in larger and multiracial populations are needed to validate
      the conclusions.

PMID- 29209771
TI  - Renal function recovery after radical nephroureterectomy for upper tract
      urothelial carcinoma.
AB  - PURPOSE: To understand the longitudinal renal function trends in patients
      undergoing radical nephroureterectomy (RNU) and identify clinicopathologic
      characteristics associated with estimated glomerular filtration rate (eGFR)
      recovery. METHODS: 147 patients were available for analysis. Longitudinal eGFR
      trends were assessed by plotting each patient's eGFR measurements over time. The
      patient population was dichotomized using eGFR < 60 ml/min/1.73 m2 versus >= 60
      ml/min/1.73 m2. Cumulative incidence and competing risk regression analysis were
      used to estimate recovery of postoperative eGFR to the preoperative level and
      identify clinicopathologic characteristics associated with eGFR recovery.
      RESULTS: Median age was 68.7 years and median preoperative eGFR was 55.9
      ml/min/1.73 m2. 63.6% were male and 95.8% were white. The cumulative incidence of
      eGFR recovery was significantly higher in patients with baseline eGFR < 60
      ml/min/1.73 m2 compared to those with baseline eGFR >= 60 ml/min/1.73 m2 (p =
      0.01), with recovery rates at 2 years of 56.6% vs. 27.7%, respectively.
      Multivariable analysis revealed that preoperative hydronephrosis (HR 1.80) and
      preoperative eGFR < 60 ml/min/1.73 m2 (HR 1.87) were associated with increased
      chance of eGFR recovery. CONCLUSION: Over half of patients with preoperative eGFR
      < 60 ml/min/1.73 m2 achieved eGFR recovery within the first 3 years after RNU,
      and hydronephrosis was a significant predictor of recovery. These findings should
      be considered when counseling patients regarding chronic kidney disease
      progression after RNU and timing of perioperative chemotherapy for high risk
      tumors.

PMID- 29209773
TI  - Effect of 8-week oral supplementation with 3-ug cyano-B12 or hydroxo-B12 in a
      vitamin B12-deficient population.
AB  - PURPOSE: We compare the effect of 8-week oral supplementation with cyano-B12
      (currently used in vitamin pills) and hydroxo-B12 (predominant form in the diet)
      in a population with nutritional vitamin B12 deficiency. METHODS: Fifty-one
      healthy Indian adults with baseline serum cobalamin < 200 pmol/L were supplied
      for 8 weeks with daily oral supplements of 3-ug cyano-B12 (n = 15), 3-ug hydroxo
      B12 (n = 16), or a placebo (n = 20). Blood at baseline, and each following week,
      was examined for total cobalamin, holotranscobalamin, methylmalonic acid, and
      homocysteine. RESULTS: The study groups did not differ at baseline and were
      characterized by [median (range)] serum cobalamin [128 (68-191) pmol/L],
      holotranscobalamin [16 (6-41) pmol/L], methylmalonic acid [0.8 (0.3-1.7) umol/L],
      homocysteine [17.9 (8.5-100.9) umol/L], and a combined indicator of B12 status
      4cB12 of - 1.65 (- 0.64 to - 4.07). The group supplemented with cyano-B12 showed
      a higher increase in total serum cobalamin than the group treated with hydroxo
      B12, while other biomarkers changed comparably in the two groups. After 8 weeks
      of treatment, the biomarker values of the supplemented groups (pooled) differed
      significantly from the placebo group. Yet, the vitamin B12 status was still poor
      [cobalamin: 168 (87-302) pmol/L; holotranscobalamin: 19 (8-45) pmol/L;
      methylmalonic acid: 0.7 (0.2-1.7) umol/L; homocysteine: 17.2 (2.6-96.8) umol/L;
      4cB12 = - 1.34 (- 0.33 to - 3.3)]. CONCLUSION: 8-week supplementation with 3-ug
      cyano-B12 elevated serum cobalamin more than 3 ug hydroxo-B12, but all other
      biomarkers changed similarly in both groups. Supplementation with 3 ug vitamin
      B12 did not reverse the low status in individuals with nutritional vitamin B12
      deficiency. CLINICAL TRIAL REGISTRY OF INDIA: REF/2017/02/013343.

PMID- 29209774
TI  - The relationship between the dietary inflammatory index and prevalence of
      radiographic symptomatic osteoarthritis: data from the Osteoarthritis Initiative.
AB  - PURPOSE: To investigate whether higher dietary inflammatory index (DII(r)) scores
      were associated with higher prevalence of radiographic symptomatic knee
      osteoarthritis in a large cohort of North American people from the Osteoarthritis
      Initiative database. METHODS: A total of 4358 community-dwelling participants
      (2527 females; mean age 61.2 years) from the Osteoarthritis Initiative were
      identified. DII(r) scores were calculated using the validated Block Brief 2000
      Food-Frequency Questionnaire and scores were categorized into quartiles. Knee
      radiographic symptomatic osteoarthritis was diagnosed clinically and
      radiologically. The strength of association between divided into quartiles
      (DII(r)) and knee osteoarthritis was investigated through a logistic regression
      analysis, which adjusted for potential confounders, and results were reported as
      odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Participants with
      a higher DII(r) score, indicating a more pro-inflammatory diet, had a
      significantly higher prevalence of radiographic symptomatic knee osteoarthritis
      compared to those with lower DII(r) score (quartile 4: 35.4% vs. quartile 1:
      24.0%; p < 0.0001). Using a logistic regression analysis, adjusting for 11
      potential confounders, participants with the highest DII(r) score (quartile 4)
      had a significantly higher probability of experiencing radiographic symptomatic
      knee osteoarthritis (OR 1.40; 95% CI 1.14-1.72; p = 0.002) compared to
      participants with the lowest DII(r) score (quartile 1). CONCLUSIONS: Higher
      DII(r) values are associated with higher prevalence of radiographic symptomatic
      knee osteoarthritis.

PMID- 29209775
TI  - Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular
      endoTHelium function: evaluation of vascular endothelium function (EARTH study).
AB  - Vascular endothelial dysfunction plays an important role in the process of
      atherosclerosis up to the final stage of plaque rupture. Vascular endothelial
      dysfunction is reversible, and can be recovered by medications and life-style
      changes. Improvement in endothelial function may reduce cardiovascular events and
      improve long-term prognosis. A total of 50 patients with stable angina and
      dyslipidemia were enrolled, including patients who had not received prior
      treatment with statins and had serum LDL-C levels >= 100 mg/dL, and patients who
      had previously received statin treatment. All agreed to register regardless of
      their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg
      and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels
      lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was
      assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index
      in the radial artery by Endo-PAT(r) 2000 (Endo-PAT(r)2000, software version
      3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally
      analyzed online by Endo-PAT(r)2000 at baseline and at 24 weeks. LDL-C and MDA-LDL
      C decreased from 112.6 +/- 23.3 to 85.5 +/- 20.2 mg/dL and from 135.1 +/- 36.4 to
      113.9 +/- 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did
      not change significantly after treatment. RH-PAT index levels significantly
      improved, from 1.60 +/- 0.31 to 1.77 +/- 0.57 (p = 0.04) after treatment, and the
      percent change of the RH-PAT index was 12.8 +/- 36.9%. Results of multivariate
      analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of
      improvement of the RH-PAT index. However, HbA1c at baseline was an independent
      predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of
      patients with high HbA1c at baseline did not improve after administration of
      rosuvastatin but it did improve in patients with low HbA1c at baseline.
      Aggressive lowering of LDL-C with rosuvastatin significantly improved the RH-PAT
      index, suggesting that it may improve endothelial function in patients with
      coronary artery disease.Clinical Trial Registration No: UMIN-CTR, UMIN000010040.

PMID- 29209776
TI  - Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes
      mice.
AB  - Hyperoxia, or supplemental oxygen, is regularly used in the clinical setting for
      critically ill patients in ICU. However, several recent studies have demonstrated
      the negative impact of this treatment in patients in critical care, including
      increased rates of lung and cardiac injury, as well as increased mortality. The
      purpose of this study was to determine the predisposition for arrhythmias and
      electrical remodeling in a type 2 diabetic mouse model (db/db), as a result of
      hyperoxia treatment. For this, db/db and their heterozygous controls were treated
      with hyperoxia (> 90% oxygen) or normoxia (normal air) for 72-h. Immediately
      following hyperoxia or normoxia treatments, mice underwent surface ECG. Excised
      left ventricles were used to assess ion channel expression, including for Kv1.4,
      Kv1.5, Kv4.2, and KChIP2. Serum cardiac markers were also measured, including
      cardiac troponin I and lactate dehydrogenase. Our results showed that db/db mice
      have increased sensitivity to arrhythmia. Normoxia-treated db/db mice displayed
      features of arrhythmia, including QTc and JT prolongation, as well as QRS
      prolongation. A significant increase in QRS prolongation was also observed in
      hyperoxia-treated db/db mice, when compared to hyperoxia-treated heterozygous
      control mice. Db/db mice were also shown to exhibit ion channel dysregulation, as
      demonstrated by down-regulation in Kv1.5, Kv4.2, and KChIP2 under hyperoxia
      conditions. From these results, we conclude that: (1) diabetic mice showed
      distinct pathophysiology, when compared to heterozygous controls, both in
      normoxia and hyperoxia conditions. (2) Diabetic mice were more susceptible to
      arrhythmia at normal air conditions; this effect was exacerbated at hyperoxia
      conditions. (3) Unlike in heterozygous controls, diabetic mice did not
      demonstrate cardiac hypertrophy as a result of hyperoxia. (4) Ion channel
      remodeling was also observed in db/db mice under hyperoxia condition similar to
      its heterozygous controls.

PMID- 29209777
TI  - Effects of aortic tortuosity on left ventricular diastolic parameters derived
      from gated myocardial perfusion single photon emission computed tomography in
      patients with normal myocardial perfusion.
AB  - Aortic tortuosity is often found on chest radiograph, especially in aged
      patients. We tested the hypothesis that aortic tortuosity was associated with LV
      diastolic parameters derived from gated SPECT in patients with normal myocardial
      perfusion. One-hundred and twenty-two patients with preserved LV ejection
      fraction and normal myocardial perfusion were enrolled. Descending aortic
      deviation was defined as the horizontal distance from the left line of the aortic
      knob to the most prominent left line of the descending aorta. This parameter was
      measured for the quantitative assessment of aortic tortuosity. Peak filling rate
      (PFR) and one-third mean filling rate (1/3 MFR) were obtained from redistribution
      images as LV diastolic parameters. Descending aortic deviation ranged from 0 to
      22 mm with a mean distance of 4.5 +/- 6.3 mm. Descending aortic deviation was
      significantly correlated with age (r = 0.38, p < 0.001) and estimated glomerular
      filtration rate (eGFR) (r = - 0.21, p = 0.02). Multivariate linear regression
      analysis revealed that eGFR (beta = 0.23, p = 0.02) and descending aortic
      deviation (beta = - 0.23, p = 0.01) were significantly associated with PFR, and
      that only descending aortic deviation (beta = - 0.21, p = 0.03) was significantly
      associated with 1/3 MFR. Our data suggest that aortic tortuosity is associated
      with LV diastolic parameters derived from gated SPECT in patients with normal
      myocardial perfusion.

PMID- 29209778
TI  - Safety and efficacy of prourokinase injection in patients with ST-elevation
      myocardial infarction: phase IV clinical trials of the prourokinase phase study.
AB  - To evaluate the safety and efficacy in terms of infarct-related artery (IRA)
      patency of prourokinase (proUK) injection within 6 h after symptom onset in
      patients with ST-elevation myocardial infarction (STEMI). A total of 1851
      patients with acute myocardial infarction were enrolled to receive thrombolytic
      therapy with proUK. Qualifying patients were injected with 20 mg proUK
      intravenously followed by intravenous infusion of 30 mg proUK within 30 min. IRA
      was evaluated by coronary angiography at 120 min after thrombolysis. The efficacy
      and safety of proUK thrombolysis were analyzed in all the enrolled patients.
      Successful clinical reperfusion was observed in 1580 patients (85.4%). The number
      of leads with ST segment elevation and the amplitude of ST segment elevation were
      significantly reduced within 24 h after thrombolytic therapy with proUK. Eighty
      three patients (4.48%) had died by the end of follow-up (7 days after
      thrombolysis), and the incidences of post-infarction angina, re-infarction or
      reocclusion, and emergency revascularization were 15.2, 4.21, and 8.27%,
      respectively. The most common bleeding complication was subcutaneous or mucosal
      bleeding and the incidence of intracranial hemorrhage was as lower as 0.32%. The
      fibrinolysis therapy with proUK is efficient and safe with very low rate of
      bleeding complications. It provides an alternative treatment options for STEMI
      patients especially in settings where primary PCI cannot be offered in a timely
      manner.

PMID- 29209779
TI  - Central regulation of brown adipose tissue thermogenesis and energy homeostasis
      dependent on food availability.
AB  - Energy homeostasis of mammals is maintained by balancing energy expenditure
      within the body and energy intake through feeding. Several lines of evidence
      indicate that brown adipose tissue (BAT), a sympathetically activated thermogenic
      organ, turns excess energy into heat to maintain the energy balance in rodents
      and humans, in addition to its thermoregulatory role for the defense of body core
      temperature in cold environments. Elucidating the central circuit mechanism
      controlling BAT thermogenesis dependent on nutritional conditions and food
      availability in relation to energy homeostasis is essential to understand the
      etiology of symptoms caused by energy imbalance, such as obesity. The central
      thermogenic command outflow to BAT descends through an excitatory neural pathway
      mediated by hypothalamic, medullary and spinal sites. This sympathoexcitatory
      thermogenic drive is controlled by tonic GABAergic inhibitory signaling from the
      thermoregulatory center in the preoptic area, whose tone is altered by body core
      and cutaneous thermosensory inputs. This circuit controlling BAT thermogenesis
      for cold defense also functions for the development of fever and psychological
      stress-induced hyperthermia, indicating its important role in the defense from a
      variety of environmental stressors. When food is unavailable, hunger-driven
      neural signaling from the hypothalamus activates GABAergic neurons in the
      medullary reticular formation, which then block the sympathoexcitatory
      thermogenic outflow to BAT to reduce energy expenditure and simultaneously
      command the masticatory motor system to promote food intake-effectively
      commanding responses to survive starvation. This article reviews the central
      mechanism controlling BAT thermogenesis in relation to the regulation of energy
      and thermal homeostasis dependent on food availability.

PMID- 29209780
TI  - Quality of work experience after angioplasty or heart surgery: a monocentric
      cohort study.
AB  - PURPOSE: The study evaluated work experience changes and its determinants after
      return to work (RTW) in angioplasty or heart surgery patients. METHODS: During a
      1-year period (2014) in a Rehabilitation Hospital in northwestern Italy, we
      approached 253 patients (19.3% of inpatients). 199 patients consented to complete
      a survey on job characteristics, job satisfaction, job involvement, illness
      perception, depression, anxiety, adherence to therapy, and sociodemographic
      characteristics. The data were analysed with paired sample t tests and random
      intercept regression models. RESULTS: 156 patients completed both the baseline
      and the 6-month follow-up assessments. After 6 months, 137 (88%) patients return
      to work (86% male, M age = 51.9 +/- 8.1). The patients predominantly underwent
      angioplasty/bypass (46%) or valve replacement/repair (38%). Work hours (WO), job
      satisfaction (JS), and job involvement (JI) significantly decreased after RTW
      (WO: t (132) = 2.07, p < 0.05; JS: t (134) = 2.56, p < 0.05; JI: t (129) = 4.14,
      p < 0.001). The decrease in work hours over time was associated with a within
      subjects decrease in psychological job demands (beta = 5.107, t (112.1) = 2.21, p
      < 0.05) and job satisfaction (beta = 2.498, t (112.92) = 2.265, p < 0.05) and an
      increase in physical job demands (beta = - 1.314, t (112.07) = - 2.416, p <
      0.05). The decrease in job satisfaction over time was related to a within
      subjects decrease in decision latitude (beta = 0.505, t (116.43) = 2.825, p <
      0.01) and an increase in psychological job demand (beta = - 0.586, t (116.78) = -
      3.141, p < 0.01). The decrease in job involvement over time was associated with a
      decrease in physical job demands (beta = 0.063, t (117.19) = 2.157, p < 0.05)
      within-subjects. CONCLUSIONS: The study showed that many patients who RTW after
      angioplasty or heart surgery have poorer work experiences relative to changes in
      psychological and physical demands and more passive roles.

PMID- 29209781
TI  - Age-dependent cognitive dysfunction in untreated hereditary transthyretin
      amyloidosis.
AB  - Central nervous system (CNS) involvement in hereditary transthyretin (TTR)
      amyloidosis has been described in patients whose disease course was modified by
      liver transplant. However, cognitive dysfunction has yet to be investigated in
      those patients. Moreover, CNS involvement in untreated patients or asymptomatic
      mutation carriers remains to be studied. A series of 340 carriers of the
      TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a
      neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS
      2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail
      making test. Cognitive deficits were identified at the individual level, after
      adjusting the neuropsychological test scores for demographic characteristics
      (sex, age, and education), based on large national normative data. The presence
      of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple
      cognitive domains. Participants were also screened for depression based on a self
      report questionnaire. The frequency of cognitive dysfunction was higher (p =
      0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older
      carriers (>= 50 years), the frequency of cognitive dysfunction was higher (p <
      0.001) in symptomatic (36%) than asymptomatic (4%) individuals. Among younger
      participants (< 50 years), the frequency of cognitive dysfunction was not
      different (p = 0.631) between symptomatic patients (2%) and asymptomatic (1%)
      carriers. This cross-sectional study shows that cognitive dysfunction is part of
      the broad spectrum of clinical manifestations in older hereditary TTR amyloidosis
      patients with peripheral polyneuropathy, even in the early stages of the disease.

PMID- 29209782
TI  - Advances in immunotherapeutic research for glioma therapy.
AB  - Gliomas are primary malignancies of the brain. Tumors are staged based on
      malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma.
      Tumors are often diagnosed once patients become symptomatic, at which time the
      lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and
      difficult to treat. Most tumors are diagnosed de novo. The gold standard of
      therapy, implemented over a decade ago, consists of fractionated radiotherapy and
      temozolomide, but unfortunately, chemotherapeutic resistance arises. Recurrence
      is common after initial therapy. The tumor microenvironment plays a large role in
      cancer progression and its manipulation can repress progression. The advent and
      implementation of immunotherapy, via manipulation and activation of cytotoxic T
      cells, have had an outstanding impact on reducing morbidity and mortality
      associated with peripheral cancers under certain clinical circumstances. An
      arsenal of immunotherapeutics is currently under clinical investigation for
      safety and efficacy in the treatment of newly diagnosed and recurrent high grade
      gliomas. These immunotherapeutics encompass antibody-drug conjugates, autologous
      infusions of modified chimeric antigen receptor expressing T cells, peptide
      vaccines, autologous dendritic cell vaccines, immunostimulatory viruses,
      oncolytic viruses, checkpoint blockade inhibitors, and drugs which alter the
      behavior of innate immune cells. Effort is focusing on determining which patient
      populations will benefit the most from these treatments and why. Research
      addressing synergism between treatment options is gaining attention. While
      advances in the treatment of glioma stagnated in the past, we may see a
      considerable evolution in the management of the disease in the upcoming years.

PMID- 29209783
TI  - Acute effect on ambulatory blood pressure from aerobic exercise: a randomised
      cross-over study among female cleaners.
AB  - PURPOSE: High occupational physical activity (OPA) is shown to increase the risk
      for elevated blood pressure, cardiovascular diseases and mortality. Conversely,
      aerobic exercise acutely lowers the blood pressure up to 25 h post exercise.
      However, it is unknown if this beneficial effect also apply for workers exposed
      to high levels of OPA. Cleaners constitute a relevant occupational group for this
      investigation because of a high prevalence of OPA and cardiovascular disease.
      Accordingly, the objective was to investigate the acute effects on ambulatory
      blood pressure from a single aerobic exercise session among female cleaners.
      METHODS: Twenty-two female cleaners were randomised to a cross-over study with a
      reference and an aerobic exercise session. Differences in 24-h, work hours,
      leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using
      repeated measure 2 * 2 mixed-models. RESULTS: After the aerobic exercise session,
      the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg
      (p < 0.01) compared to the reference session. The 24-h diastolic ABP was
      unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a
      higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise
      session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04)
      and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP
      was unaltered. CONCLUSION: A single aerobic exercise session lowered 24-h
      systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be
      beneficial for lowering the risk of hypertension among cleaners.

PMID- 29209784
TI  - AcAxl2 and AcMst1 regulate arthrospore development and stress resistance in the
      cephalosporin C producer Acremonium chrysogenum.
AB  - The filamentous fungus Acremonium chrysogenum is the primordial producer of the
      beta-lactam antibiotic cephalosporin C. This antibiotic is of major
      biotechnological and medical relevance because of its antibacterial activity
      against Gram-positive and Gram-negative bacteria. Antibiotic production during
      the lag phase of fermentation is often accompanied by a typical morphological
      feature of A. chrysogenum, the fragmentation of the mycelium into arthrospores.
      Here, we sought to identify factors that regulate the hyphal septation process
      and present the first comparative functional characterization of the type I
      integral plasma membrane protein Axl2 (axial budding pattern protein 2), a
      central component of the bud site selection system (BSSS) and Mst1 (mammalian
      Sterile20-like kinase), a septation initiation network (SIN)-associated germinal
      center kinase (GCK). Although an Acaxl2 deletion strain showed accelerated
      arthrospore formation after 96 h in liquid culture, deletion of Acmst1 led to a
      24 h delay in arthrospore development. The overexpression of Acaxl2 resulted in
      an arthrospore formation similar to the A3/2 strain. In contrast to this,
      A3/2::Acmst1 OE strain displayed an enhanced arthrospore titer. Large-scale
      stress tests revealed an involvement of AcAxl2 in controlling osmotic,
      endoplasmic reticulum, and cell wall stress response. In a similar approach, we
      found that AcMst1 plays an essential role in regulating growth under osmotic,
      cell wall, and oxidative stress conditions. Microscopic analyses and plating
      assays on media containing Calcofluor White and NaCl showed that arthrospore
      development is a stress-dependent process. Our results suggest the potential for
      identifying candidate genes for strain improvement programs to optimize
      industrial fermentation processes.

PMID- 29209785
TI  - Sediment pollution in margins of the Lake Guaiba, Southern Brazil.
AB  - Sediments are formed by deposition of organic and inorganic particles on depth of
      water bodies, being an important role in aquatic ecosystems, including
      destination and potential source of essential nutrients and heavy metals, which
      may be toxic for living organisms. The Lake Guaiba supplies water for
      approximately two million people and it is located in the metropolitan region of
      Porto Alegre, Rio Grande do Sul State, Brazil. Thus, the aim of this study was to
      evaluate the sediment pollution in the margins of Lake Guaiba in the vicinity of
      Porto Alegre city. Surface sediment was sampled in 12 sites to assess the
      concentration of several elements (C, N, P, Fe, Al, Ca, Mg, Na, K, Mn, Ba, Zn, V,
      Pb, Cu, Cr, Ni, Cd, Mo, and Se) and the mineralogical composition. Sediment in
      margins of Lake Guaiba presented predominantly (> 95%) sandy fraction in all
      samples, but with significant differences between evaluated sites. Sediments in
      the margins of Lake Guaiba showed indications of punctual water pollution with
      Pb, Cu, Cr, Ni, TOC, TKN, and P, mainly derived from urban streams that flow into
      the lake. In order to solve these environmental liabilities, public actions
      should not focus only on Guaiba, but also in the streams that flow into the lake.

PMID- 29209787
TI  - [Different levels of experience with anesthetic agents of German emergency
      physicians : Results of an online survey].
AB  - BACKGROUND AND OBJECTIVE: In 2015 practice management guidelines on prehospital
      emergency anesthesia in adults were published in Germany. The aim of the present
      study was to evaluate whether emergency physicians follow these guidelines in
      daily practice and to assess their level of experience with the use of anesthetic
      agents. MATERIAL AND METHODS: In an online survey the way of induction of
      preclinical anesthesia (including preoxygenation time and applied monitoring
      techniques) was assessed with the help of virtual scenarios based on the
      guidelines. Furthermore, the individual level of experience with specific
      anesthetic agents was estimated by the total number of anesthetic procedures
      performed with these drugs (0, 1-10, 11-25, 26-50, 51-100, and >100 procedures).
      RESULT: A total of 155 emergency physicians answered the online survey. Except
      for cardiac patients and for the preoxygenation time, we found a high accordance
      between specific algorithms proposed in the guidelines and emergency physicians'
      clinical practice. Furthermore, the median level of experience with rocuronium
      and succinylcholine was significantly higher compared to vecuronium. With respect
      to induction agents the highest level of experience was found for propofol and
      thiopental, the lowest for the combination of ketamine/propofol and midazolam.
      Generally, compared to non-anesthetists, emergency physicians had significantly
      higher levels of experience with the use of these anesthetic agents (except for
      etomidate and vecuronium). Over 94% used a 4-lead electrocardiogram (ECG), pulse
      oxymetry, non-invasive blood pressure and quantitative capnography for
      monitoring. The availability of succinylcholine was 91%, rocuronium 55%,
      vecuronium 29% and sugammadex 9%. CONCLUSION: The results of this survey
      demonstrate that clinical practice of emergency physicians is in high accordance
      with the recommendations named in the guidelines for prehospital emergency
      anesthesia in adults (except for cardiac patients and time of preoxygenation).
      With respect to the lower levels of experience of non-anesthetists in the use of
      anesthetic drugs, specific training concepts may help to further improve the
      quality of preclinical emergency care.

PMID- 29209786
TI  - Prognostic value of preprocedural 6-min walk test in patients undergoing
      transcatheter mitral valve repair-insights from the German transcatheter mitral
      valve interventions registry.
AB  - AIMS: The 6-min walk test (6 MWT) has been established as an important tool for
      functional assessment in heart failure patients. However, its prognostic impact
      on the outcome in subjects with mitral regurgitation undergoing transcatheter
      mitral valve repair is unknown. METHODS: This present work represents a sub
      analysis of the German, prospective, multicenter, Transcatheter Mitral Valve
      Interventions (TRAMI) registry. Of the main study cohort (n = 828) 326 patients
      underwent 6 MWT prior to the procedure. Patients were assigned to two groups
      depending on the preprocedural 6 MWT distance using the median (< 200 m [group 1]
      vs. >= 200 m [group 2]). RESULTS: No differences regarding procedural success (97
      vs. 96%; p = 0.71) and 30-day mortality (3 vs. 4%; p = 0.96) were observed
      between the groups. With regards to 1-year outcome, patients with a walking
      distance < 200 m had higher all-cause mortality (26 vs. 14%; p = 0.013) as
      compared to those with a 6 MWT distance 200 m. After adjustment of baseline risk
      factors, 6 MWT distance < 200 m still showed a strong trend towards increased 1
      year all-cause mortality (HR 1.63, 95% confidence interval 0.96-2.76; p = 0.071).
      CONCLUSIONS: In the present study preprocedural 6 MWT distance < 200 m showed a
      strong trend towards increased 1-year mortality in patients undergoing MitraClip
      implantation.

PMID- 29209788
TI  - [Reform of emergency physician training in Austria : Finally up to date?]
AB  - During the last 20 years Austrian prehospital emergency medical services (EMS)
      have significantly improved. The structure and organization of Austrian EMS
      comply with European standards but training requirements for prehospital EMS
      physicians are insufficient when compared with other countries. Although some EMS
      systems follow the German or Swiss postgraduate training concepts, the legal
      requirements in Austria defining the scope of mandatory training for physicians
      in the prehospital setting are only minimal. Thus, besides board certification as
      a general practitioner or specialist of any discipline, the only formal
      requirement is a 1-week theoretical course comprising some manikin simulations.
      Experience in anesthesia or intensive care medicine is still not mandatory. The
      Austrian Society of Anesthesiology, Resuscitation and Intensive Care Medicine
      (OGARI) drafted a reform paper in 2009, which was adapted by the Austrian Chamber
      of Physicians, section of emergency medicine, and subsequently presented to the
      Austrian Ministry of Health. Due to the slowness of the legislation process, the
      relevant S 40 of the Austrian Physician 's Act is still unchanged. In the
      meantime, Austrian specialist training regulations were restructured in 2015 with
      significant consequences. Due to changes in the residency programs, board
      certification and subsequent full working permit becomes more difficult to
      obtain, thus further aggravating the shortage of emergency physicians in Austria.
      In order to counteract the threatening shortage of prehospital EMS physicians,
      the OGARI section of emergency medicine was requested by the Ministry of Health
      to develop a reasonable model for how physicians could be qualified and
      subsequently employed in EMS prior to full board certification. Presently, the
      Austrian Ministry of Health, the Chamber of Physicians and medical societies are
      in discussion on whether this approach might fit into the legal framework. This
      manuscript details the development and present status as well as key points of an
      ongoing discussion on how high-quality EMS care in Austria can be safeguarded in
      the future or could even make it impossible.

PMID- 29209789
TI  - [Novel aspects of the guidelines for hemotherapy 2017 : Implications for
      anesthesiology].
AB  - Based on the German Transfusion Law, the periodically updated guidelines
      "Richtlinien zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von
      Blutprodukten" ("Hamotherapierichtlinien") are intended to provide the current
      knowledge and state of the art of blood transfusion practice in Germany. The
      novel update 2017 contains relevant changes for blood donation, especially the
      extension of the exclusion period of persons at risk for sexually transmitted
      HBV, HCV and HIV diseases to 12 months. Moreover, the guidelines provide several
      changes relevant to blood transfusion practice in anesthesiology, such as: all
      autologous hemotherapy procedures including normovolemic hemodilution, cell
      saver, and autologous blood donation and transfusion require formal registration
      at the regulatory authority. A special detailed protocol is required for every
      cell saver use. A formal quality control procedure for cell saver use is
      necessary at least every 3 months. Retransfusion of unprocessed shed blood is
      generally not permitted. Guidance is provided for the clinical situation of
      lacking consent for blood transfusion in emergency situations (under certain
      circumstances blood transfusion may still be allowed). For the first time, the
      concept of "patient blood management" is explicitly mentioned and recommended in
      the guidelines. Especially the novel regulations regarding autologous blood use
      impose new challenges in clinical practice in anesthesiology.

PMID- 29209790
TI  - [Delegation of medical activities in acute pain therapy].
AB  - Acute pain management is an interprofessional and interdisciplinary task and
      requires a good and trustful cooperation between stakeholders. Despite provisions
      in Germany according to which medical treatment can only be rendered by a
      formally qualified physician ("Arztvorbehalt"), a physician does not have to
      carry out every medical activity in person. Under certain conditions, some
      medical activities can be delegated to medical auxiliary personnel but they need
      to be (1) instructed, (2) supervised and (3) checked by the physician himself;
      however, medical history, diagnostic assessment and evaluation, indications,
      therapy planning (e.g. selection, dosage), therapeutic decisions (e. g.
      modification or termination of therapy) and obtaining informed consent cannot be
      delegated. With respect to drug therapy, monitoring of the therapy remains the
      personal responsibility of the physician, while the actual application of
      medication can be delegated. From a legal perspective, the current practice needs
      to be stressed about what is within the mandatory requirements and what is not
      when medical activities are delegated to non-medical staff. The use of standards
      of care improves treatment quality but like any medical treatment it must be
      based on the physician's individual assessment and indications for each patient
      and requires personal contact between physician and patient. Delegation on the
      ward and in acute pain therapy requires the authorization of the delegator to
      give instructions in the respective setting. The transfer of non-delegable duties
      to non-medical personnel is regarded as medical malpractice.

PMID- 29209791
TI  - Electrification of Biotechnology: Status quo.
AB  - Interfacing microbial, enzymatic, and electrochemical transformations has led to
      the new field of electrobiotechnology. Among the plethora of applications
      (including electric energy generation via pollutant removal), the synthesis of
      chemicals and energy carriers (e.g. H2) has sparked great interest. The linked
      transformation of chemical and electric energy may allow the joint utilization of
      renewable feedstock and sustainable electricity to gain commodities and fuels.
      The overall field is now referred to as bioelectrosynthesis and is a focus of
      this book. Starting with the rationale for using bioelectrosynthesis in a
      bioeconomy, this chapter provides a brief introduction to the field of
      electrobiotechnology. Subsequently, the chapter discusses the framework for
      bioelectrosynthesis, which is based on enzymes as well as microorganisms, and
      provides a definition of bioelectrosynthesis. The chapter concludes with a short
      overview on the history of the field. Graphical Abstract.

PMID- 29209792
TI  - The impact of smoking on disease measures in rheumatoid arthritis: the need for
      appropriate adjustment of time-varying confounding.
AB  - In a recent publication, Quintana-Dunque et al. studied patients with early onset
      rheumatoid arthritis (RA) and showed that baseline smoking status was inversely
      associated with disease activity and disability at 36 months. The authors
      conclude that smoking may not be as deleterious as previously considered in RA
      disease course. However, the authors fail to highlight several limitations of
      study design and analysis, including time-varying confounding, which may have a
      direct impact on results and corresponding conclusions.

PMID- 29209793
TI  - Degenerative changes after posterior cruciate ligament reconstruction are
      irrespective of posterior knee stability: MRI-based long-term results.
AB  - INTRODUCTION: Posterior cruciate ligament reconstruction (PCLR) is advocated to
      prevent an early onset of osteoarthritis. We hypothesized that posterior
      instability after PCLR correlates with degenerative changes. MATERIALS AND
      METHODS: MRIs of 42 (12 female/30 male; 39 +/- 9 years) patients were enrolled
      with a minimum 5-year follow-up (FFU) after PCLR. In addition, 25 contralateral
      and 15 follow-up MRIs (12 months after baseline) were performed. Degenerative
      changes were graded using WORMS. Posterior tibial translation (PTT) was measured
      using posterior stress radiographs. Outcome parameters included WORMS/cartilage
      subscore for the whole joint, patellofemoral (PFJ), medial (MFTJ), and lateral
      femorotibial joint (LFTJ). RESULTS: Final follow-up was 101 (range 68-168)
      months. WORMS reached 41.5 [18.5-56.8]. Regional WORMS for PFJ was significantly
      higher than MFTJ and LFTJ. Cartilage subscore yielded 7 [2.8-15]. MFTJ and PFJ
      were significantly higher than LFTJ. Primary outcome parameters were
      significantly higher than the contralateral knee (P < 0.0001) and significantly
      increased within 12 months (P = 0.0002). There was a significant correlation
      between the intraoperative degree of cartilage injury and WORMS (P < 0.0001 with
      r = 0.64) and between the number of previous surgery and the cartilage subscore
      (P = 0.03 with r = 0.32). Meniscal surgery led to a significantly higher WORMS (P
      = 0.035). Combined risk models revealed that women below the mean age had
      significantly lower WORMS (P = 0.001) and cartilage subscores (P = 0.003).
      CONCLUSIONS: Patients undergo degenerative changes after PCLR, which are
      significantly higher compared to the contralateral knee. These occur
      predominantly at PFJ/MFTJ and are irrespective of posterior stability.
      Concomitant meniscus/cartilage injuries and a high number of previous surgeries
      are further risk factors.

PMID- 29209794
TI  - Advances in therapeutic bacterial antisense biotechnology.
AB  - Antisense therapeutics are a biotechnological form of antibiotic therapy using
      chemical analogues of short single-stranded nucleic acid sequences modified to
      form stable oligomers. These molecules are termed antisense oligonucleotides
      (ASOs) because their sequence is complementary, via Watson-Crick specific base
      pairing, to their target messenger RNA (mRNA). ASOs modify gene expression in
      this sequence-dependent manner by binding to its complementary mRNA and
      inhibiting its translation into protein through steric blockage and/or through
      RNase degradation of the ASO/RNA duplex. The widespread use of conventional
      antibiotics has led to the increasing emergence of multiple drug-resistant
      pathogenic bacteria. There is an urgent need to develop alternative therapeutic
      strategies to reduce the morbidity and mortality associated with bacterial
      infections, and until recently, the use of ASOs as therapeutic agents has been
      essentially limited to eukaryotic cells, with ASOs as antibacterials having been
      largely unexplored primarily due to the poor uptake efficiency of antisense
      molecules by bacteria. There are conceptual advantages to bacterial antisense
      antibiotic therapies, including a sequence-dependent approach that allows for a
      rational design to multiple specific molecular targets. This review summarizes
      the current knowledge of antisense bacterial biotechnology and highlights the
      recent progress and the current obstacles in their development for therapeutic
      applications.

PMID- 29209796
TI  - [Spindle-cell osteosclerotic bone lesion with MDM2 amplification].
AB  - This case report presents an osteosclerotic bone lesion in a 49-year-old man with
      MDM2 amplification. The final diagnosis shows metastasis to the bones from
      stomach cancer. In primary bone tumours, the MDM2 amplifications observed have
      been described for many other tumour entities as well, and therefore do not
      exclude bone metastasis from a carcinoma.

PMID- 29209795
TI  - Exploring anaerobic environments for cyanide and cyano-derivatives microbial
      degradation.
AB  - Cyanide is one of the most toxic chemicals for living organisms described so far.
      Its toxicity is mainly based on the high affinity that cyanide presents toward
      metals, provoking inhibition of essential metalloenzymes. Cyanide and its cyano
      derivatives are produced in a large scale by many industrial activities related
      to recovering of precious metals in mining and jewelry, coke production, steel
      hardening, synthesis of organic chemicals, and food processing industries. As
      consequence, cyanide-containing wastes are accumulated in the environment
      becoming a risk to human health and ecosystems. Cyanide and related compounds,
      like nitriles and thiocyanate, are degraded aerobically by numerous bacteria, and
      therefore, biodegradation has been offered as a clean and cheap strategy to deal
      with these industrial wastes. Anaerobic biological treatments are often preferred
      options for wastewater biodegradation. However, at present very little is known
      about anaerobic degradation of these hazardous compounds. This review is focused
      on microbial degradation of cyanide and related compounds under anaerobiosis,
      exploring their potential application in bioremediation of industrial cyanide
      containing wastes.

PMID- 29209797
TI  - [Morphology of non cutaneous head and neck squamous cell carcinoma].
AB  - Head and neck squamous cell carcinoma (HNSCC) is by far the most frequent
      malignant tumor in this anatomic region. Today, HNSCC is divided into two
      morphologically, molecularly and clinically fundamentally different entities:
      conventional and virus-associated (HPV/EBV) neoplasms. Premalignant lesions of
      nonvirus-associated HNSCC include conventional leukoplakia, dysplasia and
      proliferative verrucous hyperplasia with an increasing risk for malignant
      transformation. The morphology of HNSCC comprises a spectrum of growth patterns.
      In addition, special types of HNSCC must be delineated. Recently, for virus
      associated HNSCC, some important clinicopathological specifics have become
      relevant including a separate staging system for these neoplasms. For non-virus
      associated HNSCC, new grading procedures have been proposed, which significantly
      impact on prognosis. These issues will be discussed in this review.

PMID- 29209798
TI  - [Two synchronous malignancies in a single nephrectomy specimen].
AB  - We report a case of a 65-year-old man examined for hematuria and neurologic
      symptoms. Radiologically a tumour of the kidney was suspected, with metastatic
      involvement of the brain and both lungs. The urologists then performed a
      cytoreductive nephrectomy.In histopathological examination of the nephrectomy
      specimen a clear cell renal cell carcinoma (clear cell RCC) was found. However,
      an additional focus of a high-grade adenocarcinoma was discovered that turned out
      to be a metastasis of a poor differentiated lung adenocarcinoma. This diagnosis
      was supported by positive TTF1 and napsin-A as well as good clinical
      correlations.The article summarizes the differential diagnostic considerations of
      poor differentiated adenocarcinoma of the kidney, aimed at gross and microscopic
      morphology, immunohistochemistry and clinical-pathological correlation. A review
      of literature about a tumour-in-tumour metastasis is included.

PMID- 29209799
TI  - [Chondroblastoma].
AB  - Chondroblastomas are very rare benign primary bone tumors occurring
      preferentially in the epiphyses or apophyses of long bones in children and
      adolescents. In most cases the typical histological and imaging findings lead to
      a correct diagnosis that may be substantiated by demonstrating the highly
      specific point mutation in the H3F3B gene (p.K36M), either by sequencing or
      immunohistochemistry. Recurrences occur in 5-15% of cases, postsurgical
      metastatic deposits to the lungs are very rare (<1%). Histologically "malignant"
      chondroblastomas have been reported as single case reports. The treatment of
      choice is a thorough curettage, also in the case of local relapses.

PMID- 29209800
TI  - Long-term variations of aerosol optical depth and aerosol radiative forcing over
      Iran based on satellite and AERONET data.
AB  - In this study, three different sensors of satellites including the Moderate
      Resolution Imaging Spectroradiometer (MODIS), Multi-angle Imaging
      SpectroRadiometer (MISR), and Total Ozone Mapping Spectrometer (TOMS) were used
      to study spatial and temporal variations of aerosols over ten populated cities in
      Iran. Also, the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT)
      model was used for analyzing the origins of air masses and their trajectory in
      the area. An increasing trend in aerosol concentration was observed in the most
      studied cities in Iran during 1979-2016. The cities in the western part of Iran
      had the highest annual mean of aerosol concentration. The highest aerosol optical
      depth (AOD) value (0.76 +/- 0.51) was recorded in May 2012 over Ahvaz, and the
      lowest value (0.035 +/- 0.27) was recorded in December 2013 over Tabriz. After
      Ahvaz, the highest AOD value was found over Tehran (annual mean 0.11 +/- 0.20).
      The results show that AOD increases with increasing industrial activities, but
      the increased frequency of aerosols due to land degradation and desertification
      is more powerful in Iran. The trajectory analysis by the HYSPLIT model showed
      that the air masses come from Egypt, Syria, and Lebanon and passed over the Iraq
      and then reached to Iran during summer. Aerosol radiative forcing (ARF) has been
      analyzed for Zanjan (Aerosol Robotic Network site) during 2010-2013. The ARF at
      surface and top of the atmosphere was found to be ranging from - 79 to - 10W m-2
      (average - 33.45 W m-2) and from - 25 to 6 W m-2 (average - 12.80 W m-2),
      respectively.

PMID- 29209801
TI  - [Interprofessional multistation practical training in the auditorium :
      Implementation of the national competence-based catalog of learning objectives
      for undergraduate medical education in the cross-sectorial area medicine of aging
      and the aged at the TU Dresden].
AB  - BACKGROUND: The German national competence-based catalogue of learning objectives
      for undergraduate medical education (NKLM) newly introduced in 2015, provides a
      variety of learning objectives, competences, as well as practical skills for the
      cross-sectorial area 7 "Medication of Aging and the Aged" (QB7). Against this
      background an interdisciplinary teaching concept to mediate all required teaching
      contents should be developed. OBJECTIVE: Can an interdisciplinary multistation
      practical course in the auditorium, in which different tasks and skills are
      trained at each station meet the requirements of the NKLM? MATERIAL AND METHODS:
      Evaluation by questionnaire and rating of answers on a 6-stage Likert scale.
      Analysis of the qualitative and quantitative evaluation results of 235
      participating students and 13 lecturers in 2016. RESULTS: The interdisciplinary
      multistation practical course in the auditorium is fully compliant with the NKLM.
      All theoretical and practical contents and competences could be depicted. The
      subjective learning effect was assessed by students as good (mean = 2.66; SD =
      0.94; N = 230). The available teaching time was rated as being too short in
      qualitative statements. The lecturers attested a high degree of interest by the
      students (mean = 2.15; SD = 0.86; N = 13), but criticized that the noise level
      was too loud. DISCUSSION: Compact, hands-on and interdisciplinary teaching
      concepts in the QB7 help to make the best use of human and spatial resources and
      convey all theoretical and practical teaching contents and competences from the
      NKLM; however, the planning, organization and implementation are very time
      consuming.

PMID- 29209802
TI  - [Doping for the brain].
AB  - The enhancement of physical and cognitive abilities (i. e. concentration,
      vigilance, memory) has always been desirable for humans. The term pharmacological
      neuroenhancement refers to the use of legal or nonprescription psychoactive
      substances by healthy subjects with the intention of cognitive enhancement. To
      give the most prominent example, caffeine serves worldwide as a natural
      stimulant. Brain doping, however, specifies the use of illegal substances or
      prescription drugs beyond approval with the purpose of cognitive enhancement.
      Only amphetamines, methylphenidate and modafinil have significant effects on
      attentiveness, concentration and alertness, whereas other substances, such as
      anti-dementia drugs or anti-depressants failed to demonstrate cognitive
      enhancement in healthy subjects.

PMID- 29209803
TI  - [OurPuppet - Caring support with an interactive puppet for informal caregivers :
      Opportunities and challenges in the social and technical developmental process].
AB  - BACKGROUND: The "OurPuppet" project comprises a sensor-based, interactive puppet
      that will be developed to communicate with people in need of care during a short
      period of absence of the informal caregiver. Specially qualified puppet guides
      will support the use of the new technical development. They instruct people with
      dementia and caregivers on how to use the puppet and supervise the (informal)
      care relationship through discussions on a regular basis. OBJECTIVES: The article
      shows the specific components of users' needs for which the concrete technical
      development should find answers. It also focuses on the opportunities and
      challenges for the technical and social developmental process accompanied by
      these demands. MATERIAL AND METHODS: The analysis of the users' needs is based on
      a participatory approach. Semi-structured focus group interviews were conducted
      with informal caregivers, nurses and volunteers in order to identify typical
      situations in home care settings. The interviews were paraphrased and summarized
      in order to deduce inductive categories (qualitative data analysis), which
      describe everyday situations that the technical system should address. RESULTS
      AND CONCLUSION: Such analyses provide information about the needs of potential
      users and indicate how to design such technical systems. Furthermore,
      opportunities and challenges of the development process as well as important
      contextual information were identified.

PMID- 29209804
TI  - Efferents of anterior cingulate areas 24a and 24b and midcingulate areas 24a' and
      24b' in the mouse.
AB  - The anterior cingulate cortex (ACC), constituted by areas 25, 32, 24a and 24b in
      rodents, plays a major role in cognition, emotion and pain. In a previous study,
      we described the afferents of areas 24a and 24b and those of areas 24a' and 24b'
      of midcingulate cortex (MCC) in mice and highlighted some density differences
      among cingulate inputs (Fillinger et al., Brain Struct Funct 222:1509-1532,
      2017). To complete this connectome, we analyzed here the efferents of ACC and MCC
      by injecting anterograde tracers in areas 24a/24b of ACC and 24a'/24b' of MCC.
      Our results reveal a common projections pattern from both ACC and MCC, targeting
      the cortical mantle (intracingulate, retrosplenial and parietal associative
      cortex), the non-cortical basal forebrain, (dorsal striatum, septum, claustrum,
      basolateral amygdala), the hypothalamus (anterior, lateral, posterior), the
      thalamus (anterior, laterodorsal, ventral, mediodorsal, midline and intralaminar
      nuclei), the brainstem (periaqueductal gray, superior colliculus,
      pontomesencephalic reticular formation, pontine nuclei, tegmental nuclei) and the
      spinal cord. In addition to an overall denser ACC projection pattern compared to
      MCC, our analysis revealed clear differences in the density and topography of
      efferents between ACC and MCC, as well as between dorsal (24b/24b') and ventral
      (24a/24a') areas, suggesting a common functionality of these two cingulate
      regions supplemented by specific roles of each area. These results provide a
      detailed analysis of the efferents of the mouse areas 24a/24b and 24a'/24b' and
      achieve the description of the cingulate connectome, which bring the anatomical
      basis necessary to address the roles of ACC and MCC in mice.

PMID- 29209805
TI  - Selected persistent organic pollutants (POPs) in water of River Niger: occurrence
      and distribution.
AB  - This study assessed the levels and distribution of selected persistent organic
      pollutants (POPs) in water of River Niger. The selected POPs of interest were
      organochlorine pesticides (OCPs). Fifteen representative sites along River Niger:
      three each from Gurara River (tributary) in Niger State, Lokoja (confluence) in
      Kogi State, Onitsha in Anambra State, Brass and Nicolas Rivers (tributaries) in
      Bayelsa State were selected for sampling quarterly over a 24-month period. A
      total of 240 surface and bottom water samples were collected using Van Dorn water
      sampler in the eight quarters of 2008-2009. At the Delta locations where tidal
      effects take place, high- and low-tide water samples were taken as compared to
      surface and bottom at the River Niger locations. For sample extraction, EPA
      method 3510c was employed with slight modifications. Certified reference
      standards from Accustandards USA was used for the instrument calibration and
      quantification of OCPs. The extracted samples were subjected to gas
      chromatography (GC/ECD) for identification/quantification. And Shimadzu GCMS
      QP2010 was used for confirmation. Chlordane, endosulfan, endrin and DDT
      metabolites were very prominent in the water samples, compared to HCH, dieldrin,
      and isomers which occurred at lower concentrations. The sequence in the
      concentration of the organochlorine pesticides were ?chlordane > ?DDT >
      ?endosulfan > ?endrine > ?dieldrin > ?HCH. The highest concentration of ?OCPs in
      water samples of River Niger, 1138.0 +/- 246.7 ng/L, with range 560.8-1629 ng/L
      was detected at Onitsha location, while the lowest concentration, 292.6 +/- 74.9,
      with range 181-443.0 ng/L was detected at Nicolas River. Levels of OCPs in a
      larger percentage of the samples exceeded guidelines and therefore hold potential
      harmful effects on benthic fauna, fish, and man. Abstraction of water from the
      River for drinking water treatment should be discouraged. Because of the
      potential danger, this presents, continuous monitoring of the water body and if
      possible remediation, determination of the sources of the POPs is therefore very
      necessary.

PMID- 29209806
TI  - Response to: Comparison of direct anterior, lateral, posterior and posterior-2
      approaches in total hip arthroplasty: network meta-analysis. Eur J Orthop Surg
      Traumatol, 2017 Sep 27, doi: 10.1007/s00590-017-2046-1 [Epub ahead of print].

PMID- 29209807
TI  - Clinical relevance of active straight leg raising, standing up, and walking after
      total knee arthroplasty in a cross-sectional study.
AB  - BACKGROUND: Active straight leg raising (ASLR) is used to assess restoration of
      the quadriceps muscle immediately after total knee arthroplasty (TKA). This study
      aimed to (1) compare the times required to accomplish ASLR, standing up, and
      walking after TKA, and (2) evaluate the correlation between the time required to
      accomplish ASLR and perioperative patient-related factors. METHODS: This cross
      sectional study included 271 patients (335 primary TKAs performed using the
      conventional medial parapatellar approach). Postoperative times required until
      each activity was accomplished were confirmed. Various factors that might impact
      ASLR, including prosthetic design, were also evaluated. RESULTS: Post-TKA, it
      took 1.5 +/- 0.5 days to accomplish ASLR, 1.3 +/- 0.6 days to accomplish standing
      up, and 1.4 +/- 0.7 days to accomplish walking. There were no significant
      correlations between any factor and ASLR. Strong correlations were found between
      the times required to accomplish standing up and walking (p < 0.0001, r = 0.804).
      There were no significant correlations between the times required to accomplish
      ASLR and standing up/walking. A longer time was necessary for ASLR accomplishment
      than for standing up (p < 0.001) and walking (p < 0.001). Standing up was
      accomplished earlier than walking (p = 0.008). CONCLUSIONS: There was no delay in
      post-TKA ASLR accomplishment compared with previous reports. No factors affecting
      ASLR during the perioperative period suggested that ASLR was controlled by
      factors other than knee joint-related factors. ASLR was not correlated with
      standing up/walking; hence, the clinical significance of ASLR immediately after
      TKA for early ambulation is unclear. LEVEL OF EVIDENCE: Prognostic study, Level
      II.

PMID- 29209808
TI  - Minimal influence of the anterolateral knee ligament on anterior and rotational
      laxity of the knee: a cadaveric study.
AB  - Knee laxity may be impacted by rupture of the anterolateral knee ligament (ALL).
      The goal of this study was to measure tibial translation and rotation as a
      function of the status of the ALL and the anterior cruciate ligament (ACL). Five
      pairs of fresh frozen cadaver specimens were analyzed. The knee was positioned in
      20 degrees  flexion. Calibrated posteroanterior forces and internal/external
      torques were successively applied. Anterior tibial translation and total
      internal/external tibial rotation were measured with a navigation system. Three
      conditions were used in each knee: intact ACL and ALL, transection of ACL or ALL
      (randomly assigned to each knee of a pair), and transection of both ligaments.
      The primary outcome criterion was the increase in tibial rotation at 8 Nm. The
      mean increase in tibial rotation at 8 Nm was 0.8 degrees  after transecting the
      ALL only, 1.2 degrees  after transecting the ACL only, and 0.8 degrees  after
      transecting both ligaments. The mean increase in anterior tibial translation at
      250 N was 1.2 mm after transecting the ALL only, 9.0 mm after transecting the ACL
      only, and 6.1 mm after transecting both ligaments. There was no significant
      increase in the tibial rotation or anterior tibial translation after transecting
      the ALL only or after transecting the ALL in ACL-deficient knees. The expected
      role of ALL in controlling anterior or rotational tibia motion could not be
      confirmed.

PMID- 29209809
TI  - Reduction and temporary stabilization of Tile C pelvic ring injuries using a
      posteriorly based external fixation system.
AB  - Tile C pelvic ring injuries are challenging to manage even in the most
      experienced hands. The majority of such injuries can be managed using
      percutaneous reduction techniques, and the posterior ring can be stabilized using
      percutaneous transiliac-transsacral screw fixation. However, a subgroup of
      patients present with inadequate bony corridors, significant sacral zone 2
      comminution or significant lateral/vertical displacement of the hemipelvis
      through a complete sacral fracture. Percutaneous strategies in such circumstances
      can be dangerous. Those patients may benefit from prone positioning and open
      reduction of the sacral fracture with fixation through tension band plating or
      lumbo-pelvic fixation. Soft tissue handling is critical, and direct reduction
      techniques around the sacrum can be difficult due to the complex anatomy and the
      fragile nature of the sacrum making clamp placement and tightening a challenge.
      In this paper, we propose a mini-invasive technique of indirect reduction and
      temporary stabilization, which is soft tissue friendly and permits maintenance of
      reduction during definitive fixation surgical.

PMID- 29209810
TI  - A comparison of the MeltPro(r) HPV Test with the Cobas(r) HPV Test for detecting
      and genotyping 14 high-risk human papillomavirus types.
AB  - The clinical performance of the newly developed MeltPro(r) HPV Test, based on
      multicolor melting curve analysis, was evaluated and compared with the
      commercially available Cobas(r) HPV Test for detection of HPV and genotyping of
      HPV-16 and HPV-18. A total of 1647 cervical samples were analyzed with both
      tests. The agreement values were 96.2% for HPV detection, 99.6% for HPV-16
      identification, and 99.7% for HPV-18 identification. All genotyping results from
      MeltPro(r) HPV Test showed that HPV-52, HPV-58, and HPV-16 were the most common
      types in this study. Intra-laboratory reproducibility studies showed 97.8%
      agreement while inter-laboratory reproducibility studies showed 96.9% agreement
      for the MeltPro(r) HPV Test. The MeltPro(r) HPV Test and Cobas(r) HPV Test are
      highly correlative and are useful for monitoring HPV infection.

PMID- 29209811
TI  - The nucleotide sequence of a recombinant tomato yellow leaf curl virus strain
      frequently detected in Sicily isolated from tomato plants carrying the Ty-1
      resistance gene.
AB  - In July 2016, an aggressive syndrome of tomato yellow leaf curl disease was
      reported in Sicily in tomato plants carrying the Ty-1 resistance gene. A total of
      34 samples were collected and analyzed. Twenty-seven out of the 34 samples
      analyzed appeared to contain only recombinant molecules. One full sequence was
      obtained after cloning. Alignments and plot similarity analysis showed that the
      genome of the recombinant, named TYLCV-IL[IT:Sic23:16], was mostly derived from
      tomato yellow leaf curl virus (TYLCV), with a small region of 132 nucleotides in
      the non-coding region between the stem-loop and the start of the V2 ORF replaced
      by 124 nucleotides derived from a virus of a different species, tomato yellow
      leaf curl Sardinia virus. All plants in which the new recombinant was detected
      belonged to resistant tomato cultivars.

PMID- 29209812
TI  - Genome characterization of an Argentinean isolate of alfalfa leaf curl virus.
AB  - We investigated the molecular characteristics of an Argentinean isolate of
      alfalfa leaf curl virus (ALCV-Arg), a virus of the genus Capulavirus in the
      family Geminiviridae that was isolated from alfalfa plants showing dwarfism. The
      genome was found to be 2,750 nucleotides in length. In pairwise comparisons, this
      ALCV isolate shared 83.2% to 92.6% sequence identity with European ALCV isolates.
      Sequence comparisons and phylogenetic analysis showed that this isolate combines
      features of strains A and B of ALCV. Recombination analysis showed that ALCV-Arg
      is a recombinant isolate that was generated by intraspecific recombination
      between ALCV strains A and B. The results of this study not only show that ALCV
      Arg is unique because it combines features of strains A and B but also show that
      ALCV naturally infects this forage crop on the American continent.

PMID- 29209813
TI  - FSP1-specific SMAD2 knockout in renal tubular, endothelial, and interstitial
      cells reduces fibrosis and epithelial-to-mesenchymal transition in murine STZ
      induced diabetic nephropathy.
AB  - Extracellular matrix deposition during tubulointerstitial fibrosis (TIF), a
      central pathological process in patients with diabetic nephropathy (DN), is
      driven by locally activated, disease-relevant myofibroblasts. Myofibroblasts can
      arise from various cellular sources, e.g., tubular epithelial cells via a process
      named epithelial-to-mesenchymal transition (EMT). Transforming growth factor beta
      1 (TGF-beta1) and its downstream Smad signaling play a critical role in both TIF
      and EMT. Whereas Smad3 is one central mediator, the role of the other prominently
      expressed variant, Smad2, is not completely understood. In this study, we sought
      to analyze the role of renal Smad2 in the development of TIF and EMT during
      streptozotocin-induced DN by using a fibroblast-specific protein 1 (FSP1)
      promotor-driven SMAD2 knockout mouse model with decreased tubular, endothelial,
      and interstitial Smad2 expression. In contrast to wild-type diabetic mice,
      diabetic SMAD2 knockout mice showed the following features: (1) significantly
      reduced DN and TIF (shown by KIM1 expression; periodic acid Schiff staining;
      collagen I and III, fibronectin, and connective tissue growth factor deposition);
      (2) significantly reduced tubular EMT-like changes (e.g., altered Snail1, E
      cadherin, matrix metalloproteinase 2, and vimentin deposition); and (3)
      significantly decreased expression of myofibroblast markers (alpha-smooth muscle
      actin, FSP1). As one mechanism for the protection against diabetes-induced TIF
      and EMT, decreased Smad3 protein levels and, as a possible consequence, reduced
      TGF-beta1 levels were observed in diabetic SMAD2 knockout mice. Our findings thus
      support the important role of Smad2 for pro-fibrotic TGF-beta/Smad3 signaling in
      experimental DN.

PMID- 29209814
TI  - Teleconsultation in type 1 diabetes mellitus (TELEDIABE).
AB  - AIMS: The growing incidence of diabetes and the need to contain healthcare costs
      empower the necessity to identify new models of care. Telemedicine offers an
      acknowledged instrument to provide clinical health care at a distance, increasing
      patient compliance and the achievement of therapeutical goals. The objective was
      to test the feasibility and the efficacy in the improvement of the glycemic
      control of the teleconsultation for patients with type 1 diabetes mellitus.
      METHODS: A randomized open-label, parallel arms, controlled trial was conducted
      in two diabetes centers in Italy. Participants affected by type 1 diabetes
      mellitus have been randomly (1:1) assigned to receive their visits as standard or
      a web-based care. Patients in the teleconsultation group can arrange their
      appointments on a Web site and can also have access to web educational courses or
      to nutritional and psychological counseling. The primary outcome was the
      assessment of glycemic control by HbA1c measurement after a 12-month follow-up.
      RESULTS: Overall 74 participants were followed for 1 year. HbA1c changes were not
      statistically different within (p = 0.56 for standard care group; p = 0.45 for
      telemedicine group) and between (p = 0.60) groups when considering differences
      from baseline to the end of the study. Patients randomized to teleconsultation
      reported reduced severe hypoglycemic episodes (p = 0.03). In addition, they were
      largely satisfied with the activities, perceived a good improvement in the self
      management of the diabetes, and reported to have a time saving and a cost
      reduction. CONCLUSIONS: In conclusion, TELEDIABE proposes a new system for the
      management of patients with type 1 diabetes mellitus.

PMID- 29209815
TI  - Portrait of women with type 1 or type 2 diabetes of childbearing age attending
      diabetes clinics in Italy: the AMD-Annals initiative.
AB  - AIM: To describe characteristics relevant in case of an unplanned pregnancy for
      T1D or T2D women of childbearing age. METHODS: We analyzed the 2011 AMD-Annals
      dataset, compiling information from 300 clinics (28,840 T1D patients and 532,651
      T2D patients). A risk score of unfavorable conditions for pregnancy included
      HbA1c > 8.0%; BMI >= 35; systolic BP >= 140 mmHg or diastolic BP >= 90 mmHg;
      microalbuminuria/proteinuria; use of statins, ACE inhibitors, ARB; use of
      diabetes drugs other than metformin/insulin. RESULTS: The proportion of T2D cases
      increased from 30.8% (95% CI 29.9-32.4) at age 18-30 years to 67.5% (66.6-68.5)
      at age 36-45 years. The proportion of women with HbA1c < 7.0% was 20.4% (20.0
      20.8) in T1D and 43.4% (42.8-43.9) in T2D women. Furthermore, 47.6% (47.0-48.3)
      of T1D women and 34.5% (33.9-35.0) of T2D women had HbA1c >= 8.0%. The prevalence
      of obesity (BMI >= 30) was sevenfold higher among T2D than T1D women [49.9% (49.4
      50.5) and 7.4% (7.2-7.5), respectively]. T2D women were more likely to have
      hypertension or microalbuminuria than T1D women. Almost half of the T2D women
      were taking drugs not approved during pregnancy. At least one unfavorable
      condition for starting a pregnancy was present in 51% of T1D women of
      childbearing age and in 66.7% of T2D women. CONCLUSIONS: Women with either T1D or
      T2D of childbearing age in Italy were far from the ideal medical condition for
      conception. Our data strongly support the need for counseling all women with
      diabetes about pregnancy planning.

PMID- 29209816
TI  - Gas-phase alkyl and N-alkylamino cation affinities of anionic alpha-oxygen
      nucleophiles (H n XO-; X = N, P, As, O, S, Se, F, Cl, Br; n = 0-2): a theoretical
      G2(+)M study.
AB  - In this work, we studied anionic alpha-oxygen nucleophiles in which there was an
      atom of with one or more unshared lone-pair electrons from groups 15-17 and
      periods 2-4 of the periodic table positioned adjacent to the negative attacking
      oxygen (i.e., H n XO-; X = N, P, As, O, S, Se, F, Cl, Br; n = 0-2); these
      nucleophiles were termed "alpha-agents." Specifically, we investigated the gas
      phase simple alkyl cation affinities (ACAs) and the simple N-alkylamino cation
      affinities (NAAMCAs) of these alpha-agents theoretically via the modified G2(+)M
      method. Our calculations indicate that the O-C bond of CH3OXH n is somewhat
      similar to that of iPrOXH n (n = 0, 1, 2; X = N, P, As, O, S, Se, F, Cl, Br).
      Also, steric repulsion is an important influence on these cation affinities. It
      appears that the kinetic gas-phase alpha effect in the SN2 reactions of interest
      cannot be explained by the thermodynamic proton affinity or the affinity (SuA) of
      the anionic or neutral nucleophile (Nu) for the substrate cation, as the gas
      phase ACA (NAAMCA) was found to be linearly correlated with the PA for the alpha
      agents, similar to the previously reported linear correlation of the gas-phase
      ACA (NAAMCA) with the PA for normal nucleophiles.

PMID- 29209817
TI  - Analysis of road development and associated agricultural land use change.
AB  - Development of road network is one of the strongest drivers of habitat
      fragmentation. It interferes with ecological processes that are based on material
      and energy flows between landscape patches. Therefore, changes in temporal
      patterns of roads may be regarded as important landscape-level environmental
      indicators. The aim of this study is to analyze road development and associated
      agricultural land use change near the town of Erdemli located in the eastern
      Mediterranean coast of Turkey. The study area has witnessed an unprecedented
      development of agriculture since the 2000s. This process has resulted with the
      expansion of the road network. Associations between agricultural expansion and
      road development were investigated. High-resolution satellite images of 2004 and
      2015 were used to analyze spatial and temporal dimensions of change. Satellite
      images were classified using a binary approach, in which land areas were labeled
      as either "agriculture" or "non-agriculture." Road networks were digitized
      manually. The study area was divided into 23 sublandscapes using a regular grid
      with 1-km cell spacing. Percentage of landscape (PL) for agriculture and road
      density (RD) metrics were calculated for the earlier (2004) and later (2015)
      years. Metric calculations were performed separately for each of the 23
      sublandscapes in order to understand spatial diversity of agriculture and road
      density. Study results showed that both RD and PL exhibited similar increasing
      trends between 2004 and 2015.

PMID- 29209818
TI  - Water quality of stormwater generated from an airport in a cold climate, function
      of an infiltration pond, and sampling strategy with limited resources.
AB  - Monitoring pollutants in stormwater discharge in cold climates is challenging. An
      environmental survey was performed by sampling the stormwater from Lulea Airport,
      Northern Sweden, during the period 2010-2013, when urea was used as a main
      component of aircraft deicing/anti-icing fluids (ADAFs). The stormwater collected
      from the runway was led through an oil trap to an infiltration pond to store
      excess water during precipitation periods and enhance infiltration and water
      treatment. Due to insufficient capacity, an emergency spillway was established
      and equipped with a flow meter and an automatic sampler. This study proposes a
      program for effective monitoring of pollutant discharge with a minimum number of
      sampling occasions when use of automatic samplers is not possible. The results
      showed that 90% of nitrogen discharge occurs during late autumn before the water
      pipes freeze and during snow melting, regardless of the precipitation during the
      remaining months when the pollutant discharge was negligible. The concentrations
      of other constituents in the discharge were generally low compared to guideline
      values. The best data quality was obtained using flow controlled sampling.
      Intensive time-controlled sampling during late autumn (few weeks) and snow
      melting (2 weeks) would be sufficient for necessary information. The flow meters
      installed at the rectangular notch appeared to be difficult to calibrate and gave
      contradictory results. Overall, the spillway was dry, as water infiltrated into
      the pond, and stagnant water close to the edge might be registered as flow. Water
      level monitoring revealed that the infiltration capacity gradually decreased with
      time.

PMID- 29209819
TI  - Developing reference criteria for the ecological status of West African rivers.
AB  - Awareness of sustainable management of water and its biological resources is
      rising in West Africa, but application of effective tools for biomonitoring and
      detecting habitats at risk in aquatic ecosystems is limited. In this study, we
      provide key environmental descriptors to characterize reference sites by applying
      the following "a priori criteria" (physical and chemical, hydro-morphological,
      and land use parameters) by exploring their potential to determine suitable
      reference sites. Using data collected from 44 sites, we identified 37 criteria
      that reliably identify reference conditions in semi-arid rivers by reflecting the
      impacts of multiple pressures ranging from low to very high intensity of human
      uses and impairments. We integrated all these impacts in an overall pressures
      index, which showed that protected areas can reasonably be considered as credible
      reference sites as far as they show low overall impact levels from cumulative
      pressures. We recommend that development of bio-indicator standards should be
      based on the collection and integration of all the available information,
      especially quantitative, spatially-explicit data, from benthic macroinvertebrates
      and fish. Rigorous standardization of bio-indicator protocols will make them more
      easily applicable for management and conservation of aquatic ecosystem resources
      in semi-arid zones of Africa.

PMID- 29209820
TI  - Spirosoma terrae sp. nov., Isolated from Soil from Jeju Island, Korea.
AB  - The taxonomic position of bacterial strain, designated 15J9-4T, recovered from a
      beach soil sample on Jeju Island, South Korea, was established using a polyphasic
      approach. Strain 15J9-4T was assigned to phylum Bacteroidetes within the family
      Cytophagaceae based on 16S rRNA gene similarities. The closest phylogenetic
      relatives with validly published names were Spirosoma panaciterrae Gsoil 1519T
      (94.2% similarity) and Spirosoma luteolum 16F6ET (94.1%). Cells were rod-shaped,
      Gram-stain-negative, and non-motile. The isolate grew on NA, R2A, TSA, and LB
      agar. The temperature limits for growth were 10 and 30  degrees C with an optimum
      at 25  degrees C and the pH range was 7-8. Menaquinone MK-7 was the predominant
      respiratory quinone. The major cellular fatty acids comprised summed feature 3
      (C16:1 omega6c/C16:1 omega7c, 30.2%), C16:1 omega5c (22.2%), iso C15:0 (12.9%),
      and C16:0 (8.8%). Phosphatidylethanolamine was identified as the major polar
      lipid. The G+C content of the genomic DNA was 48.4 mol%. The results obtained
      from the polyphasic analyses allowed for the genotypic and phenotypic
      differentiation of strain 15J9-4T from recognized Spirosoma species. Therefore,
      the isolate is considered to represent a novel species in the genus Spirosoma,
      for which the name Spirosoma terrae sp. nov. is proposed. The type strain is 15J9
      4T (= KCTC 52035T = JCM 31994T).

PMID- 29209821
TI  - Hemolytic Escherichia coli Inhibits Swarming and Differentiation of Proteus
      mirabilis.
AB  - Swarming is a hallmark of Proteus mirabilis, whether common gram-negative bacilli
      affect the swarming of P. mirabilis is still unclear. In this study, we found
      that P. mirabilis swarming was inhibited by Escherichia coli ATCC25922, but was
      not affected by Klebsiella pneumoniae, Acinetobacter baumannii, or Pseudomonas
      aeruginosa strains. The migration distance of P. mirabilis when mixed with E.
      coli ATCC25922 was strongly reduced, and the inhibition of the swarming of P.
      mirabilis by E. coli ATCC25922 was dependent on cell density. In addition,
      initiation of P. mirabilis swarming was delayed by E. coli ATCC25922. Among
      clinical isolates, including gram-negative bacilli and gram-positive cocci, only
      hemolytic E. coli inhibited the swarming of P. mirabilis. In summary, hemolytic
      E. coli inhibited the swarming and differentiation of P. mirabilis.

PMID- 29209822
TI  - Sodium Polyanethol Sulfonate Modulates Natural Transformation of SigH-Expressing
      Staphylococcus aureus.
AB  - Expression of genes required for natural genetic competence in Staphylococcus
      aureus is controlled by an alternative transcription sigma factor, SigH. However,
      even in the SigH-expressing cells, the DNA transformation efficiency varies
      depending on culture conditions. We report here that cells grown in the
      competence-inducing medium (CS2 medium) exhibit enlarged morphology with
      disintegrated cell walls. Notably, an autolysis inhibitor, Sodium Polyanethol
      Sulfonate (SPS), facilitated transformation in CS2 medium in a dose-dependent
      manner, suggesting the involvement of the cell wall metabolism in transformation.
      However, the transformation efficiency of cells grown in TSB was not improved by
      physical or enzymatic damage on the cell walls.

PMID- 29209823
TI  - Autologous arteriovenous fistulas for hemodialysis using microsurgery techniques
      in children weighing less than 20 kg.
AB  - BACKGROUND: This study aimed to describe the efficiency and longevity of
      arteriovenous fistula (AVF) for hemodialysis (HD) in children weighing <=20 kg.
      METHODS: We collected data of all AVFs created using microsurgery techniques
      between 1988 and 2015. Success was considered as the ability to use the AVF for
      HD. Primary and secondary patency rates were measured. RESULTS: Forty-eight AVFs
      (35 forearm, 13 upper arm) were created in 41 children with a median weight of
      13.5 kg (range 5.5-20). The need for a second AVF was significantly higher in
      younger and thinner children at the time of AVF creation (p = 0.046 and p =
      0.019, respectively). Successful use for HD occurred in 42 AVFs (87.5%), while
      six (12.5%) resulted in failure for early thrombosis or nonmaturation. Median
      time to first cannulation was 18.8 weeks (range 2-166.3). Primary and secondary
      patency rates at 1, 5, and 10-year follow-ups were 54.2%, 29.2%, and 13.7%; and
      85.4%, 57.7%, and 33%, respectively. Almost one third of thromboses after first
      AVF cannulation were observed at kidney transplantation (KT) perioperatively. At
      the end of the follow-up (median duration 5.07 years, range 0-17.95), one patient
      was still on HD via AVF, two died of unrelated reason, and 38 were transplanted
      one of whom returned to HD with a new AVF. CONCLUSIONS: AVF using microsurgery
      techniques is feasible in young children, showing an early failure rate of 12.5%.
      Time to first cannulation may be rather long, but secondary patency is excellent.
      Thrombosis rate is high during KT.

PMID- 29209824
TI  - The 2017 ESC/EACTS guidelines on the management of valvular heart disease : What
      is new and what has changed compared to the 2012 guidelines?
AB  - Numerous new data on the diagnosis and management of valvular heart disease
      published since 2012 made an update of the practice guidelines of the European
      Society of Cardiology and European Association of Cardiothoracic Surgery
      necessary. This was particularly the case for the use of catheter interventional
      treatment, indications for intervention in asymptomatic patients, medical
      treatment and organization of care. This review summarizes the most important
      changes in the recommendations.

PMID- 29209825
TI  - Performance of 4 years of population-based mammography screening for breast
      cancer combined with ultrasound in Tyrol / Austria.
AB  - BACKGROUND: Systems for the delivery of screening mammography vary among
      countries and these differences can influence screening effectiveness. We
      evaluated the performance of organized mammography screening for breast cancer
      combined with ultrasound in Tyrol / Austria, an approach that differs from many
      other population-based screening programs. METHODS: Data on women aged 40-69
      years screened in the period from June 2008 to May 2012 were collected within the
      framework of an organized screening program. A total of 272,555 invitations were
      sent to the target population living in Tyrol and 176,957 screening examinations
      were performed. We analyzed the main performance indicators as defined by
      European Union (EU) guidelines and some important estimates of harms. RESULTS:
      The estimated 2-year participation rate was 56.9%. As ultrasound is implemented
      as second-line screening procedure, 76.2% of all women screened underwent
      supplementary ultrasound. In total 2322 women were recalled for further
      assessment (13.1 per 1000 screens) and 1351 biopsies were performed (7.6 per 1000
      screens). The positive predictive value was 28.2% for assessment and 48.5% for
      biopsies. The cancer detection rate was 3.7 per 1000 screens and the proportion
      of all stage II+ screen-detected cancers was 35.5%. The interval cancer rate was
      0.33 and 0.47 per 1000 screens in the first and second years, respectively. The
      estimated cumulative risk for a false positive screening result and an
      unnecessary biopsy for women following the invitation approach was 21.1% and
      9.4%, respectively. CONCLUSION: The performance of our population-based screening
      approach combining mammography and ultrasound is very favorable and potential
      harm is kept very low compared to other European mammography screening programs
      for breast cancer.

PMID- 29209826
TI  - Volumetric modulated arc therapy (VMAT) to deliver nodal irradiation in breast
      cancer patients.
AB  - To evaluate feasibility, safety, toxicity profile and dosimetric results of
      volumetric modulated arc therapy (VMAT) to deliver regional nodal irradiation
      (RNI) after either mastectomy or breast conservation (BCS) in high-risk breast
      cancer patients. Between January 2015 and January 2017, a total of 45 patients
      were treated with VMAT to deliver RNI together with whole breast or post
      mastectomy radiotherapy. The fractionation schedule comprised 50 Gy in 25
      fractions given to supraclavicular and axillary apex nodes and to whole breast
      (after BCS) or chest wall (after mastectomy). Two opposite 50 degrees -60 degrees
      width arcs were employed for breast ad chest wall irradiation, while a single
      VMAT arc was used for nodal treatment. Treatment was generally well tolerated.
      Acute skin toxicity was G2 in 13.3% of patients. Late skin toxicity consisted of
      G1 induration/fibrosis in six patients (13.3%) and G2 in 1 (2.2%). Dosimetric
      results were consistent in terms of both target coverage and normal tissue
      sparing. In conclusion, VMAT proved to be a feasible, safe and effective strategy
      to deliver RNI in breast cancer patients after either BCS or mastectomy with
      promising dosimetric results and a mild toxicity profile.

PMID- 29209827
TI  - Hemostasis, endothelial stress, inflammation, and the metabolic syndrome.
AB  - Obesity and the metabolic syndrome (MS) are two of the pressing healthcare
      problems of our time. The MS is defined as increased abdominal obesity in concert
      with elevated fasting glucose levels, insulin resistance, elevated blood
      pressure, and plasma lipids. It is a key risk factor for type 2 diabetes mellitus
      (T2DM) and for cardiovascular complications and mortality. Here, we review work
      demonstrating that various aspects of coagulation and hemostasis, as well as
      vascular reactivity and function, become impaired progressively during chronic
      ingestion of a western diet, but also acutely after meals. We outline that both
      T2DM and cardiovascular disease should be viewed as inflammatory diseases and
      describe that chronic overload of free fatty acids and glucose can trigger
      inflammatory pathways directly or via increased production of ROS. We propose
      that since endothelial stress and increases in platelet activity precede
      inflammation and overt symptoms of the MS, they are likely the first hit. This
      suggests that endothelial activation and insulin resistance are probably
      causative in the observed chronic low-level metabolic inflammation, and thus both
      metabolic and cardiovascular complications linked to consumption of a western
      diet.

PMID- 29209829
TI  - Adaptation to proprioceptive targets following visuomotor adaptation.
AB  - In the following study, we asked if reaches to proprioceptive targets are updated
      following reach training with a gradually introduced visuomotor perturbation.
      Subjects trained to reach with distorted hand-cursor feedback, such that they saw
      a cursor that was rotated or translated relative to their actual hand movement.
      Following reach training trials with the cursor, subjects reached to Visual (V),
      Proprioceptive (P) and Visual + Proprioceptive (VP) targets with no visual
      feedback of their hand. Comparison of reach endpoints revealed that reaches to VP
      targets followed similar trends as reaches to P targets, regardless of the
      training distortion introduced. After reaching with a rotated cursor, subjects
      adapted their reaches to all target types in a similar manner. However, after
      reaching with a translated cursor, subjects adapted their reach to V targets
      only. Taken together, these results show that following training with a
      visuomotor distortion, subjects primarily rely on proprioceptive information when
      reaching to VP targets. Furthermore, results indicate that reach adaptation to P
      targets depends on the distortion presented. Training with a rotation distortion
      leads to changes in reaches to both V and P targets, while a translation
      distortion, which introduces a constant discrepancy between visual and
      proprioceptive estimates of hand position throughout the reach, affects changes
      to V but not P targets.

PMID- 29209828
TI  - Regulation of immunometabolism in adipose tissue.
AB  - Adipose tissue has emerged as a major player in driving obesity-related
      inflammatory response. In obesity, chronic infiltration of macrophages in adipose
      tissue mediates local and systemic inflammation and acts as a key contributor to
      insulin resistance. In the past few years, adipose tissue plasticity and
      remodeling capacity has been studied extensively to develop therapeutic targets
      to combat obesity and related metabolic dysfunction. Progress in understanding
      the potential of adipocytes and contribution of macrophages and other immune
      cells to control immunometabolism in disease state has provided us new potential
      intervention targets to explore such as the formation of heat-producing beige
      adipocytes in white adipose tissue and the polarization of macrophages from an
      inflammatory toward an anti-inflammatory phenotype. Initiation and progression of
      inflammatory signaling in fat pads is complex, broad, and often functions in a
      tissue/cell type-specific manner. We have also realized the importance of
      location, coordinated role of tissue cross-talk, and physiological state of the
      fat pad in these processes. There has been significant progress in understanding
      how adipose tissue regulates these crucial processes and maintains metabolic
      homeostasis such as identification of fat depot-specific regulation of energy
      metabolism, mediators of macrophage polarization, role of gut-derived antigens,
      and consequences of diet and calorie restriction on adipose tissue metabolic and
      thermogenic potential.

PMID- 29209830
TI  - Regulation of mesenchymal signaling in palatal mucosa differentiation.
AB  - Epithelial differentiation is thought to be determined by mesenchymal components
      during embryogenesis. In mice, palatal mucosa showed the region-specific
      keratinization pattern along antero-posterior axis. However, developmental
      mechanisms involved in oral mucosa differentiation with fine tuning of
      keratinization are not elucidated yet. To reveal this developmental mechanism,
      first, we conducted tissue recombination assay of the palate at E16 for 2 days
      which revealed that epithelial differentiation with specific localization of CK10
      is modulated by mesenchymal components. Based on the results, we propose that
      mesenchymal signaling would determine the presumptive fate of developing palatal
      epithelium in spatiotemporal manner. Genome-wide screening analysis using laser
      micro-dissection to collect spatiotemporal specific molecules between anterior
      and posterior palate suggested Meox2 in the posterior mesenchymal tissue to be a
      candidate regulator controlling epithelial differentiation. To examine the
      detailed spatiotemporal function of Meox2, we employed in vitro organ cultivation
      with the loss- and gain-of-function studies at E14.5 for 2 and 4 days,
      respectively. Our results suggest that posteriorly expressed Meox2 modulates non
      keratinized epithelial differentiation through complex signaling regulations in
      mice palatogenesis.

PMID- 29209831
TI  - Kinetic Basis of Cis- and Trans-Allostery in GLUT1-Mediated Sugar Transport.
AB  - A growing body of evidence demonstrates that GLUT1-mediated erythrocyte sugar
      transport is more complex than widely assumed and that contemporary
      interpretations of emergent GLUT1 structural data are incompatible with the
      available transport and biochemical data. This study examines the kinetic basis
      of one such incompatibility-transport allostery-and in doing so suggests how the
      results of studies examining GLUT1 structure and function may be reconciled.
      Three types of allostery are observed in GLUT1-mediated, human erythrocyte sugar
      transport: (1) exofacial cis-allostery in which low concentrations of
      extracellular inhibitors stimulate sugar uptake while high concentrations inhibit
      transport; (2) endofacial cis-allostery in which low concentrations of
      intracellular inhibitors enhance cytochalasin B binding to GLUT1 while high
      concentrations inhibit binding, and (3) trans-allostery in which low
      concentrations of ligands acting at one cell surface stimulate ligand binding at
      or sugar transport from the other surface while high concentrations inhibit these
      processes. We consider several kinetic models to account for these phenomena. Our
      results show that an inhibitor can only stimulate then inhibit sugar uptake if
      (1) the transporter binds two or more molecules of inhibitor; (2) high-affinity
      binding to the first site stimulates transport, and (3) low-affinity binding to
      the second site inhibits transport. Reviewing the available structural,
      transport, and ligand binding data, we propose that exofacial cis-allostery
      results from cross-talk between multiple, co-existent ligand interaction sites
      present in the exofacial cavity of each GLUT1 protein, whereas trans-allostery
      and endofacial cis-allostery require ligand-induced subunit-subunit interactions.

PMID- 29209832
TI  - Minimally invasive esophagectomy: a propensity score-matched analysis of
      semiprone versus prone position.
AB  - BACKGROUND: The preferred surgical approach for esophageal cancer is a minimally
      invasive transthoracic esophagectomy with a two-field lymph node dissection. The
      thoracoscopic phase may be performed either in prone- or in left lateral
      decubitus (LLD) position. Prone positioning has been associated with better
      pulmonary outcomes compared to LLD positioning; however, conversion to a classic
      thoracotomy is more difficult. The semiprone position has been proposed as an
      alternative approach. METHODS: A retrospective review of a prospectively
      maintained database (2008-2014) was performed to compare postoperative
      complications, surgical radicality, and lymph node yield between patients who
      underwent three-stage minimally invasive transthoracic esophagectomy in either
      the prone or semiprone position. Comparative analyses were conducted before and
      after propensity score matching. RESULTS: One hundred and twenty-one patients
      were included. In total, 82 patients underwent minimally invasive esophagectomy
      (MIE) in semiprone position and 39 patients in prone position. After propensity
      score matching, both groups consisted of 39 patients. The operative time in the
      semiprone group was longer (368 vs. 225 min, P < 0.001) and in this group the
      lymph node yield was significantly higher (16 (range 6-80) vs. 13 (range 3-33), P
      = 0.019). There were no statistically significant differences regarding radical
      resections, postoperative complications, and hospital stay. CONCLUSION: The use
      of semiprone positioning in MIE is safe, feasible, and at least comparable to MIE
      in prone position in terms of oncological clearance and postoperative
      complications.

PMID- 29209833
TI  - Fine motor ability and psychiatric disorders in youth.
AB  - Impaired fine motor ability has been linked to several domains of
      psychopathology. However, studies validating the specificity of this association
      among several categorical psychiatric disorders are still needed. The aim of this
      study was to assess differences in fine motor ability performance among four non
      overlapping groups of psychiatric disorders and a group of typical developing
      comparisons (TDC). Our sample consisted of 2035 subjects aged 6-14-year-old.
      Diagnoses of psychiatric disorders were performed with the Development and Well
      Being Assessment (DAWBA). Five non-overlapping groups without comorbidity were
      formed: phobic disorders (n = 101), distress disorders (n = 82), attention
      deficit hyperactivity disorder (ADHD) (n = 133), oppositional defiant
      disorder/conduct disorder (ODD/CD) (n = 52) and one group of typical developing
      comparisons (TDC) (n = 1667). Fine motor ability was evaluated by three tasks:
      sequential finger-thumb opposition, Oseretsky, and pronation/supination tests.
      Each task was assessed by total time to perform the movement and levels of
      accuracy, fluency, symmetry, precision, and coordination. We found that, when
      compared to TDC, the ADHD group performed more poorly in total fine motor ability
      (mean difference = - 0.28; p = 0.014), time to complete the task (mean difference
      = 0.36; p < 0.001), accuracy (mean difference = - 0.30; p = 0.005), fluency (mean
      difference = - 0.26; p = 0.03), symmetry (mean difference - 0.25; p = 0.04),
      precision (mean difference = - 0.26; p = 0.026), and coordination (mean
      difference = - 0.25; p = 0.042). The ADHD group also took more time to complete
      the task than the ODD/CD group (mean difference = 0.45; p = 0.037). No other
      significant between-group differences were found. Additional analyses showed
      those differences were statistically significant for all ADHD dimensions. Our
      results suggest that children with ADHD present impairments in all aspects of
      fine motor abilities compared to TDC, a difference not found in other psychiatric
      disorders.

PMID- 29209834
TI  - Breast cancer survivors: return to work and wage loss in selected hospitals in
      Malaysia.
AB  - PURPOSE: This study aimed, firstly, to assess the determinants of return to work
      (RTW), secondly, to explore the amount of annual wage loss, and finally, to
      discover the determinants of wage loss among breast cancer (BC) survivors.
      METHODS: A cross-sectional study design was used in this research. The data was
      collected via interview using a validated questionnaire. Logistic regression
      models were developed to discover the significant determinants of RTW and of wage
      loss among BC survivors. RESULTS: A total of 256 BC survivors were included in
      this study. The analysis showed that there was a 21% loss of or reduction in mean
      income within 1 year after diagnosis. The significant predictors of RTW are being
      a government employee, having reduced wages or wage loss, and if the case had
      been diagnosed 1 year or more ago. Being a private sector employee and having a
      late stage of cancer was a barrier to RTW. The main risk factors for reduced
      wages or wage loss were belonging to the age group of 40-59 years, being of
      Chinese or Indian ethnicity, having low educational status, and not returning to
      work. However, belonging to the higher monthly income group (earning > RM 2000)
      is a protective factor against the risk of reduced wages or wage loss.
      CONCLUSIONS: Non-RTW and wage loss after diagnosis of BC may result in the
      survivors experiencing a significant financial burden. Assessment of these
      patients is becoming more crucial because more women participate in the workforce
      in Malaysia nowadays and because BC is managed using multiple treatment
      modalities with their consequences could lead to long absences from work.

PMID- 29209835
TI  - Patient-clinician communication among patients with stage I lung cancer.
AB  - PURPOSE: Limited data exist about patient-centered communication (PCC) and
      patient-centered outcomes among patients who undergo surgery or stereotactic body
      radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We aimed
      to examine the relationship between PCC and decision-making processes among NSCLC
      patients, using baseline data from a prospective, multicenter study. METHODS:
      Patients with stage 1 NSCLC completed a survey prior to treatment initiation. The
      survey assessed sociodemographic characteristics, treatment decision variables,
      and patient psychosocial outcomes: health-related quality of life (HRQOL),
      treatment self-efficacy, decisional conflict, and PCC. RESULTS: Fifty-two percent
      (n = 85) of 165 individuals planned to receive SBRT. There were no baseline
      differences detected on patient psychosocial outcomes between those who planned
      to receive SBRT or surgery. All participants reported high HRQOL (M = 72.5, SD =
      21.3) out of 100, where higher scores indicate better functioning; high self
      efficacy (M = 1.5, SD = 0.5) out of 6, where lower numbers indicate higher self
      efficacy; minimal decisional conflict (M = 15.2, SD = 12.7) out of 100, where
      higher scores indicate higher decisional conflict; and high levels of patient
      centered communication (M = 2.4, SD = 0.8) out of 7 where higher scores indicate
      worse communication. Linear regression analyses adjusting for sociodemographic
      and clinical variables showed that higher quality PCC was associated with higher
      self-efficacy (beta = 0.17, p = 0.03) and lower decisional conflict (beta = 0.42,
      p < 0.001). CONCLUSIONS: Higher quality PCC was associated with higher self
      efficacy and lower decisional conflict. Self-efficacy and decisional conflict may
      influence subsequent health outcomes. Therefore, our findings may inform future
      research and clinical programs that focus on communication strategies to improve
      these outcomes.

PMID- 29209836
TI  - Accuracy of cystatin C for the detection of abnormal renal function in children
      undergoing chemotherapy for malignancy: a systematic review using individual
      patient data.
AB  - PURPOSE: We conducted a systematic review and individual patient data (IPD) meta
      analysis to examine the utility of cystatin C for evaluation of glomerular
      function in children with cancer. METHODS: Eligible studies evaluated the
      accuracy of cystatin C for detecting poor renal function in children undergoing
      chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies
      shared IPD. We calculated the correlation between log cystatin C and GFR
      stratified by study and measure of cystatin C. We dichotomized the reference
      standard at GFR 80 ml/min/1.73m2 and stratified cystatin C at 1 mg/l, to
      calculate sensitivity and specificity in each study and according to age group (0
      4, 5-12, and >= 13 years). In sensitivity analyses, we investigated different GFR
      and cystatin C cut points. We used logistic regression to estimate the
      association of impaired renal function with log cystatin C and quantified
      diagnostic accuracy using the area under the ROC curve (AUC). RESULTS: Six
      studies, which used different test and reference standard thresholds, suggested
      that cystatin C has the potential to monitor renal function in children
      undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children)
      showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%),
      although use of a GFR cut point of < 60 ml/min/1.73m2 (data only available from
      two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The
      AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic
      accuracy appeared to decrease with age. CONCLUSIONS: Cystatin C has better
      diagnostic accuracy than creatinine as a test for glomerular dysfunction in young
      people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for
      it to replace current reference standards for predicting clinically relevant
      impairments that may alter dosing of important nephrotoxic agents.

PMID- 29209838
TI  - IMP3 expression in NSCLC brain metastases demonstrates its role as a prognostic
      factor in non-neuroendocrine phenotypes.
AB  - Brain metastases from NSCLC are associated with a poor prognosis, and local
      radiotherapy is the most effective therapeutic strategy. The oncofetal protein
      IMP3 has been studied extensively, and evidence suggests that its expression is
      related to shorter overall survival and a more aggressive phenotype in solid
      malignancies. Here, the prognostic role of IMP3 was investigated in a cohort of
      patients with NSCLC brain metastases in correlation with survival and tumor
      histotype. A series of 42 NSCLC brain metastases samples was analyzed by tissue
      microarray and immunohistochemical staining for IMP3. IMP3 expression was
      associated with shorter overall survival in the whole series and in subgroups of
      metastases from non-neuroendocrine pulmonary malignancies and adenocarcinoma
      metastases. These results indicated that IMP3 is a strong prognostic factor in
      non-neuroendocrine brain metastases and in particular in patients with
      adenocarcinoma metastases.

PMID- 29209839
TI  - Correction to: Telomere length of gallbladder epithelium is shortened in patients
      with congenital biliary dilatation: measurement by quantitative fluorescence in
      situ hybridization.
AB  - In the original publication of this article, Fig. 5 was published with incorrect
      color of the approximate lines of CBD and Control.

PMID- 29209840
TI  - The implantable cardiac monitor and pocket infection.

PMID- 29209837
TI  - Emerging enzymatic targets controlling angiogenesis in cancer: preclinical
      evidence and potential clinical applications.
AB  - Angiogenesis has always been considered as a fundamental therapeutic target for
      inhibiting tumor growth and metastasis. To date, anti-angiogenic treatments that
      have been approved are principally based on either administration of monoclonal
      antibodies targeting the vascular endothelial growth factor/vascular endothelial
      growth factor receptor axis or multikinase inhibitors. However, a growing body of
      evidence is pointing out the role of different classes of enzymes involved in
      tumor-driven angiogenesis, whose inhibition in preclinical models has already
      shown encouraging results. This review provides an overview on the current
      knowledge of potential enzymatic targets involved in tumor-driven angiogenesis
      and the potential clinical applications deriving from their modulation.
      Metalloproteinase and nitric oxide synthase inhibitors have been found to be,
      respectively, inefficacious or unsuitable for clinical applications. Conversely,
      early clinical studies evaluating the inhibition of heparanase, nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase, lysyl oxidase (LOX) and
      angiotensin-converting enzyme (ACE) have shown promising results. Therefore,
      preliminary evidence indicates that heparanase, NADPH oxidase, LOX and ACE might
      represent potential targets for anticancer therapy.

PMID- 29209841
TI  - A Novel Method for Correcting Non-uniform/Poor Illumination of Color Fundus
      Photographs.
AB  - Retinal fundus images are often corrupted by non-uniform and/or poor illumination
      that occur due to overall imperfections in the image acquisition process. This
      unwanted variation in brightness limits the pathological information that can be
      gained from the image. Studies have shown that poor illumination can impede human
      grading in about 10~15% of retinal images. For automated grading, the effect can
      be even higher. In this perspective, we propose a novel method for illumination
      correction in the context of retinal imaging. The method splits the color image
      into luminosity and chroma (i.e., color) components and performs illumination
      correction in the luminosity channel based on a novel background estimation
      technique. Extensive subjective and objective experiments were conducted on
      publicly available DIARETDB1 and EyePACS images to justify the performance of the
      proposed method. The subjective experiment has confirmed that the proposed method
      does not create false color/artifacts and at the same time performs better than
      the traditional method in 84 out of 89 cases. The objective experiment shows an
      accuracy improvement of 4% in automated disease grading when illumination
      correction is performed by the proposed method than the traditional method.

PMID- 29209842
TI  - Impact of distinct factors affecting serum homocysteine levels in preeclamptic
      women.

PMID- 29209843
TI  - Monocultural sowing in mesocosms decreases the species richness of weeds and
      invertebrates and critically reduces the fitness of the endangered European
      hamster.
AB  - Intensive cereal monoculture is currently the main cause of biodiversity decline
      in Europe. However, it is difficult to disentangle the effects of intensive
      monoculture (e.g. pesticide use, mechanical ploughing and reduced protective
      cover), let alone evaluate how far the reduction of crop diversity affects
      biodiversity. It remains unclear to which extent the consequent decrease in food
      resources affects farmland biodiversity, and particularly vertebrate species. We
      therefore designed this study in mesocosms to investigate the effects of
      monoculture crops (organic wheat or corn seeds) and mixed crops (a combination of
      organic wheat, corn, sunflower and alfalfa seeds) on (1) the species richness of
      weeds and invertebrates and (2) the reproductive success of the European hamster
      (Cricetus cricetus), a critically endangered umbrella species of European
      farmlands. We found a negative impact of organic monoculture crops on plant and
      invertebrate species richness, with values respectively 38% and 28% lower than
      those obtained for mixed organic crops. The reproductive success of hamsters was
      reduced by 82% in monoculture mesocosms. These results highlight that monoculture
      per se can be detrimental for farmland biodiversity (i.e. from plants to
      vertebrates), even before taking into account the use of pesticide and
      mechanization. We believe that future research should further consider how food
      reduction in agroecosystems affects farmland wildlife, including vertebrates.
      Moreover, we argue that conservation actions must focus on restoring plant
      diversity on farmland to reverse the observed trend in farmland wildlife decline.

PMID- 29209844
TI  - A new method for quantifying the phylogenetic redundancy of biological
      communities.
AB  - The increasing use of phylogenetic methods in community ecology recognizes that
      accumulated evolutionary differences among species mirror, to some extent,
      ecological processes. The scope of this work is thus to propose a new method for
      the measurement of community-level phylogenetic redundancy, which takes into
      account the branching pattern of the underlying phylogeny. Like for functional
      redundancy, a measure of phylogenetic redundancy can be described as a normalized
      measure in the range (0-1) that relates the observed community-level phylogenetic
      diversity to the value of a hypothetical assemblage with the same abundance
      distribution of the focal community in which all species had independent
      evolution. Therefore, phylogenetic redundancy can be interpreted as the diversity
      decrease that is obtained by taking into account the evolutionary relationships
      among species in the calculation of diversity. The behavior of the proposed
      method, for which we provide a simple R function called 'phyloredundancy', was
      evaluated with published data on Alpine plant communities along a primary
      succession on a glacier foreland in northern Italy. As shown by our results, the
      method accounts for the length of shared branches in the phylogeny, producing a
      coherent framework for describing the evolutionary relationships within a species
      assemblage. Being based on classical diversity measures, which have been used in
      ecology for decades, it also has a great potential for future research in
      phylogenetic community ecology.

PMID- 29209845
TI  - Energy efficiency of acetone, butanol, and ethanol (ABE) recovery by heat
      integrated distillation.
AB  - Acetone, butanol, and ethanol (ABE) is an alternative biofuel. However, the
      energy requirement of ABE recovery by distillation is considered elevated (> 15.2
      MJ fuel/Kg-ABE), due to the low concentration of ABE from fermentation broths
      (between 15 and 30 g/l). In this work, to reduce the energy requirements of ABE
      recovery, four processes of heat-integrated distillation were proposed. The
      energy requirements and economic evaluations were performed using the
      fermentation broths of several biocatalysts. Energy requirements of the processes
      with four distillation columns and three distillation columns were similar
      (between 7.7 and 11.7 MJ fuel/kg-ABE). Double-effect system (DED) with four
      columns was the most economical process (0.12-0.16 $/kg-ABE). ABE recovery from
      dilute solutions by DED achieved energy requirements between 6.1 and 8.7 MJ
      fuel/kg-ABE. Vapor compression distillation (VCD) reached the lowest energy
      consumptions (between 4.7 and 7.3 MJ fuel/kg-ABE). Energy requirements for ABE
      recovery DED and VCD were lower than that for integrated reactors. The energy
      requirements of ABE production were between 1.3- and 2.0-fold higher than that
      for alternative biofuels (ethanol or isobutanol). However, the energy efficiency
      of ABE production was equivalent than that for ethanol and isobutanol (between
      0.71 and 0.76) because of hydrogen production in ABE fermentation.

PMID- 29209846
TI  - Micelle-mediated transport disturbance providing extracellular strategy for
      alleviating n-butanol stress on Escherichia coli.
AB  - One barrier inhibiting further progress in biofuel production is the toxicity of
      biofuels towards their producers. It is promising to apply gene-based
      intracellular techniques to engineer better strains with higher organic solvent
      tolerance. These methods are, however, complex. In the present study, we
      developed a simple, manageable, and commercial extracellular prototypal strategy
      to alleviate n-butanol (n-BuOH) stress on Escherichia coli via a micelle-mediated
      transport disturbance. When the concentration of sodium dodecyl sulfate, a
      typical anionic surfactant, is high enough to form micelles, n-BuOH will be
      trapped into/onto the micelles, and the negative charge prevents the n-BuOH from
      approaching the cells. Our study provides an extracellular strategy to relieve
      the stress from n-BuOH, and it also exhibits a new angle to advance microbial
      factories through extracellular routines.

PMID- 29209847
TI  - Prediction of venous thromboembolism in newly diagnosed patients treated for
      lymphoid malignancies: validation of the Khorana Risk Score.
AB  - The utility of the venous thromboembolism (VTE) risk assessment model known as
      the Khorana Risk Score (KRS) in patients with lymphoid malignancies receiving
      outpatient chemotherapy is not defined. We evaluated the association of the KRS
      with VTE in patients treated for diffuse large B cell lymphoma (DLBCL) or Hodgkin
      lymphoma (HL). Retrospective analyses were performed in 428 patients, 241 of whom
      were newly diagnosed with DLBCL and 187 of whom had HL. During the initial
      therapy, 64 (15%) patients developed VTE and 56 died during follow-up. More VTE
      events occurred in patients with DLBCL than in patients with HL. According to the
      KRS, 364 (85%) and 64 (15%) patients were considered to be at intermediate risk
      and high risk of VTE development, respectively. The high-risk KRS patients were
      more often diagnosed with HL than DLBCL (19 vs. 10%, P = 0.0143). The KRS did not
      discriminate between high- and intermediate-risk patients with respect to VTE
      occurrence (17 vs. 15%, P = 0.5868). In our patients, the KRS did not adequately
      predict VTE (positive predictive value 15%, negative predictive value 82% and C
      statistic 0.51). In the multivariate analysis, bulky disease (OR 2.34; 95% CI
      1.62-3.36, P < 0.0001), poor prognostic disease (OR 1.32; 95% CI 1.01-1.74, P =
      0.049) and DLBCL histological subtype (OR 1.61; 95% CI 1.17-2.19, P = 0.003) were
      all significantly associated with the VTE development. In this cohort of patients
      with lymphoid malignancies, the KRS did not adequately stratify or predict VTE
      events in patients at a higher risk of VTE. This finding suggests the need for
      the development of a disease-specific VTE assessment model.

PMID- 29209848
TI  - Development of a finite-element eye model to investigate retinal hemorrhages in
      shaken baby syndrome.
AB  - Retinal hemorrhages (RH) are among injuries sustained by a large number of shaken
      baby syndrome victims, but also by a small proportion of road accident victims.
      In order to have a better understanding of the underlying of RH mechanisms, we
      aimed to develop a complete human eye and orbit finite element model. Five
      occipital head impacts, at different heights and on different surfaces, and three
      shaking experiments were conducted with a 6-week-old dummy (Q0 dummy). This
      allowed obtaining a precise description of the motion in those two specific
      situations, which was then used as input for the eye model simulation. Results
      showed that four parameters (pressure, Von Mises stress and strain, 1st principal
      stress) are relevant for shaking-fall comparison. Indeed, in the retina, the
      softest shaking leads to pressure that is 4 times higher than the most severe
      impact (1.43 vs. 0.34 kPa). For the Von Mises stress, strain and 1st principal
      stress, this ratio rises to 4.27, 6.53 and 14.74, respectively. Moreover, regions
      of high stress and strain in the retina and the choroid were identified and
      compared to what is seen on fundoscopy. The comparison between linear and
      rotational acceleration in fall and shaking events demonstrated the important
      role of the rotational acceleration in inducing such injuries. Even though the
      eye model was not validated, the conclusion of this study is that compared to
      falls, shaking an infant leads to extreme eye loading as demonstrated by the
      values taken by the four mentioned mechanical parameters in the retina and the
      choroid.

PMID- 29209849
TI  - Comments on: blood product transfusion in emergency department patients: a case
      control study of practice patterns and impact on outcome.
AB  - Clinical decision makings according studies result require the valid and correct
      data collection, andanalysis. However, there are some common methodological and
      statistical issues which may ignore by authors. In individual matched case-
      control design bias arising from the unconditional analysis instead of
      conditional analysis. Using an unconditional logistic for matched data causes the
      imposition of a large number of nuisance parameters which may result in seriously
      biased estimates.

PMID- 29209850
TI  - Theoretical study of the reactions of the hydroselenyl radical (HSe?) with the
      selenenic radical (HSeO?).
AB  - The formation of selenium species in some biological processes involves the
      generation of ionic and radical intermediates such as RSe?, RSe-, RSeO?, and RSeO
      , among others. We performed a theoretical study of the possible mechanisms for
      the reaction of the two simplest Se radicals-the hydroselenyl (HSe?) and
      selenenic (HSeO?) radicals, in which the possible products, intermediates, and
      transition-state structures were investigated. Density functional theory (DFT)
      was applied at the B3LYP/6-311++G(3df,3pd) level and the Ahlrichs Coulomb fitting
      basis sets were employed with an effective core potential (ECP) for both Se
      atoms. The same procedure was used to calculate the electronic density. All
      calculations were also performed using the M06-2X functional, which describes
      weaker bonds better than B3LYP does. In the reaction of interest, the so-called
      CR complex (HSe....SeOH) is formed initially. After passing through the
      transition state TS1, cis-HSeSeOH is obtained as a product. If a low barrier is
      then overcome (passing through the transition state TS32), the trans-HSeSeOH
      species is obtained. The CR complex can also rearrange into the intermediate INT
      after overcoming the barrier presented by the transition state TS2. Additionally,
      the decomposition of INT to H2O and 1Se2 is possible through another transition
      state. This reaction is not included in this study. We also observed a second
      possible route for the conversion of INT to one of the HSeSeOH species; this
      route occurs through two pathways (with transition states TS31 and TS32). A
      comparison of some of the results with those obtained for sulfur analogs along
      the same pathways is also presented in this work. Graphical abstract Electronic
      envelopes for HSeO? and HSe? radicals.

PMID- 29209851
TI  - Elevated parathyroid hormone levels after successful parathyroidectomy for
      primary hyperparathyroidism: a clinical review.
AB  - INTRODUCTION: Surgery for primary hyperparathyroidism (PHPT) is traditionally
      deemed to be successful if serum calcium levels return to normal 6 months after
      parathyroidectomy. Regular monitoring of serum calcium and parathyroid hormone
      (PTH) in the follow-up of patients after parathyroidectomy for PHPT has drawn
      attention to the presence of a normocalcemic group of patients with elevated PTH
      (NCePTH) during the post-operative period. The etiological factors and mechanisms
      underlying this condition, its consequences, and the possibility of treatment are
      the object of this study. MATERIALS AND METHODS: We conducted an unlimited PubMed
      search updated on March 31, 2017, which yielded 1628 results. We selected 37
      articles, 33 of which included cases of NCePTH in their series and 23 performed
      statistical studies to assess factors associated with NCePTH. RESULTS: The
      maximum mean prevalence of NCePTH in the various series was 23.5%, ranging from 3
      to 46%. Many factors were associated with NCePTH. The most important were higher
      pre-operative PTH, low pre-operative 25 (OH) D3, lower pre-operative creatinine
      clearance and greater adenoma weight. The origin of NCePTH may be multifactorial,
      since several factors were implicated in the etiology. NCePTH does not seem to be
      related to an increase in PHPT recurrence, although this possibility should not
      be dismissed. Vitamin D deficiency should be corrected. Treatment with calcium
      supplements seems to be clearly beneficial. CONCLUSION: The prevalence of NCePTH
      is high. The causes of secondary hyperparathyroidism should be investigated
      carefully. Patients require treatment and long-term follow-up.

PMID- 29209852
TI  - Clinical predictors for satisfaction with incus vibroplasty: a preliminary study.
AB  - OBJECTIVE: We aimed to evaluate the subjective satisfaction after incus
      vibroplasty and to determine predictive factors affecting patient satisfaction in
      sensorineural hearing loss. DESIGN: A retrospective review of audiological data
      and an additional survey about subjective satisfaction after surgery were
      performed in 14 patients who underwent incus vibroplasty surgery. A numeric
      rating scale reflecting the degree of satisfaction after incus vibroplasty,
      compared with experiences using a conventional hearing aid, was used. Patients
      who showed median or better satisfaction were deemed the highly satisfied (HS)
      group, and the others were deemed the less satisfied (LS) group. To find the
      predictive factors correlated with satisfaction for incus vibroplasty,
      comparative analysis between two groups was performed. RESULTS: We found that the
      numeric rating scale for satisfaction was variable, ranged from 0 to 10, and was
      negatively correlated with age at operation (p < 0.01). The HS group had a
      younger age (27.6 +/- 22.2 years) and better preoperative air conduction
      threshold at 250 Hz (20.7 +/- 7.9 dB) than the LS group (68.0 +/- 9.7 years, 32.1
      +/- 10.7 dB). The LS group (13.6 +/- 9.9 dB) showed a larger change of air-bone
      gap after surgery than the HS group (5.7 +/- 6.7 dB) at 250 Hz (p = 0.12).
      CONCLUSIONS: Age at operation and the preoperative air conduction threshold level
      at 250 Hz appear to be potential predictive factors for subjective satisfaction
      with incus vibroplasty. Furthermore, more conservative selection of candidates
      and caution during surgery, considering inevitable air-bone gap development
      postoperatively, may be necessary to achieve higher satisfaction for incus
      vibroplasty.

PMID- 29209853
TI  - 3D endoscopic ear surgery: a clinical pilot study.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of a new high-resolution 3D
      endoscope in endoscopic ear and lateral skull base surgery. METHODS: Eight
      patients, five women and three men, were included in this clinical pilot
      prospective study. Their age was 38 +/- 17.3 years (mean +/- SD, range 17-54
      years). The right side was involved in five cases, and the left side in three
      cases. There were three cases of chronic otitis, one case of cholesteatoma of the
      external auditory canal, one case of otosclerosis, one case of cochlear implant
      surgery, and two cases of stage 2 vestibular schwannoma operated on with a
      retrosigmoid approach to preserve hearing. RESULTS: There were no intraoperative
      or postoperative complications. The new system was used during all procedures
      without the necessity to switch to a 2D mode. The surgeons felt comfortable using
      the system and its major advantages were considered to be in measuring the
      distances for ossicular chain reconstruction and in the sense of depth provided
      in the middle ear and cerebellopontine angle. CONCLUSION: The sense of depth
      provided by the 3D system is effective in both middle ear and lateral skull base
      surgery. Further improvements (smaller and/or more angled endoscopes) should be
      considered for future developments in endoscopic ear surgery.

PMID- 29209854
TI  - Does the approach to economic evaluation in health care depend on culture,
      values, and institutional context?

PMID- 29209855
TI  - Osteoporotic hip fractures in Black South Africans: a regional study.
AB  - : Osteoporotic hip fractures are thought to be rare in Blacks however, this study
      from South Africa shows a significant increase in the number of hip fracture in
      Blacks. With the expected increase in older people, osteoporotic fractures will
      pose a major health problem and screening guidelines needed to be implemented.
      INTRODUCTION: Developing countries are predicted to bear the burden of
      osteoporosis in the coming decades. This study was undertaken to review earlier
      reports that osteoporotic hip fractures are rare in Black Africans. METHODS: In
      an observational study, the incidence rates and relative risk ratios (RRR) of
      osteoporotic hip fractures were calculated in the Black population, aged 60 years
      and older, residing in the eThekwini region of South Africa. All Black subjects,
      presenting with a minimal trauma hip fracture to five public hospitals in the
      region, entered the study. Descriptive statistics were applied to show
      differences in age and sex. RESULTS: Eighty-seven subjects were enrolled in the
      study with a mean age of 76.5 +/- 10.5 years and the sex ratio of women to men
      was 2.5:1. Although men were younger than women, this was not significant (74.2
      +/- 12.3 vs. 77.4 +/- 9.6 years, p = 0.189). The age-adjusted rate was 69.2 per
      100,000 p.a. for women and 73.1 per 100,000 p.a. for men. There was a significant
      increase in the relative risk ratios for hip fractures after the age of 75 years
      in the total cohort and in women and men. Except for the 65-69-year age group,
      there was no significant difference in the age-adjusted RRR between women and
      men. CONCLUSION: This study represents the largest number of hip fractures
      recorded in Black Africans. Although the incidence rate is approximately tenfold
      higher than previously recorded, it remains amongst the lowest globally. A
      national registry inclusive of private and public sector is required to establish
      the true incidence rate of hip fractures in Black Africans.

PMID- 29209856
TI  - Accelerated whole brain intracranial vessel wall imaging using black blood fast
      spin echo with compressed sensing (CS-SPACE).
AB  - OBJECTIVE: Develop and optimize an accelerated, high-resolution (0.5 mm
      isotropic) 3D black blood MRI technique to reduce scan time for whole-brain
      intracranial vessel wall imaging. MATERIALS AND METHODS: A 3D accelerated T1
      weighted fast-spin-echo prototype sequence using compressed sensing (CS-SPACE)
      was developed at 3T. Both the acquisition [echo train length (ETL), under
      sampling factor] and reconstruction parameters (regularization parameter, number
      of iterations) were first optimized in 5 healthy volunteers. Ten patients with a
      variety of intracranial vascular disease presentations (aneurysm,
      atherosclerosis, dissection, vasculitis) were imaged with SPACE and optimized CS
      SPACE, pre and post Gd contrast. Lumen/wall area, wall-to-lumen contrast ratio
      (CR), enhancement ratio (ER), sharpness, and qualitative scores (1-4) by two
      radiologists were recorded. RESULTS: The optimized CS-SPACE protocol has ETL 60,
      20% k-space under-sampling, 0.002 regularization factor with 20 iterations. In
      patient studies, CS-SPACE and conventional SPACE had comparable image scores both
      pre- (3.35 +/- 0.85 vs. 3.54 +/- 0.65, p = 0.13) and post-contrast (3.72 +/- 0.58
      vs. 3.53 +/- 0.57, p = 0.15), but the CS-SPACE acquisition was 37% faster (6:48
      vs. 10:50). CS-SPACE agreed with SPACE for lumen/wall area, ER measurements and
      sharpness, but marginally reduced the CR. CONCLUSION: In the evaluation of
      intracranial vascular disease, CS-SPACE provides a substantial reduction in scan
      time compared to conventional T1-weighted SPACE while maintaining good image
      quality.

PMID- 29209857
TI  - Feeding Behavior of an Aquatic Snail as a Simple Endpoint to Assess the Exposure
      to Cadmium.
AB  - One of the aims of ecotoxicology is the assessment of the effects of chemicals on
      the ecosystems. Bioassays assessing lethality are frequently used in
      ecotoxicology, however they usually employ supra-environmental toxic
      concentrations. Toxicity tests employing behavioral endpoints may present a
      balance between simplicity (i.e., laboratory bioassays) and complexity (i.e.,
      relevant ecological effects). The aim of this study was to develop a feeding
      behavioral bioassay with the aquatic snail, Potamopyrgus antipodarum, which
      included a 2 days exposure to cadmium, followed by a 9 days post-exposure
      observational period. Several behavioral feeding endpoints were monitored,
      including percentage of actively feeding animals, percentage of animals in food
      quadrants and a mobility index. The percentage of actively feeding animals was
      reduced by the four cadmium treatments (0.009, 0.026, 0.091 and 0.230 mg Cd/L)
      with the stronger effect in the highest concentration. The two highest cadmium
      concentrations significantly reduced the percentage of animals in food quadrants
      and the mobility index. Therefore, the percentage of actively feeding animals was
      the most sensitive endpoint to cadmium toxicity as the four cadmium
      concentrations caused a significant decrease in this endpoint. It is concluded
      that feeding behavior is a useful endpoint to detect the exposure of aquatic
      snails to cadmium.

PMID- 29209858
TI  - Direct and Indirect Anthropogenic Contamination in Water Sources: Evaluation of
      Chromosomal Stability and Cytotoxicity Using the Allium cepa Test.
AB  - Increasing industrialization and urbanization has deteriorated water quality
      around the world. Nowadays, evaluation of the effects of chemical compounds using
      bioassays is a critical step in the hazard identification assessment. Thus, this
      work aimed to determine the genetic damage caused by different types of
      anthropogenic contamination in a river's water in Brazil. Two points (P1 and P2)
      and two periods (referred as direct and indirect anthropogenic contamination)
      were evaluated in Allium cepa roots. MI was increased (p < 0.05) in both points
      in the indirect anthropogenic contamination and decreased in the indirect
      anthropogenic contamination periods. Moreover, parameters as DNA instability (CA
      and MN) were observed in both periods indicating substances in the water with
      mutagenic, genotoxic, and cytotoxic potential. Interestingly, a 20-fold increase
      in CA frequencies were observed in P1 and P2 in the second collection period
      (direct anthropogenic contamination) (p < 0.05). In conclusion, our data
      indicated that anthropogenic activities in the area contributed to contaminate
      this water source. Moreover, direct anthropogenic contamination maximized the
      damage, posing a possible hazard to population health.

PMID- 29209859
TI  - Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind, randomised
      clinical trial.
AB  - BACKGROUND: The trial aimed to evaluate the efficacy and safety of Spicae
      aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the
      flowering tops of Lavandula latifolia, as compared to placebo in adult patients
      with acute bronchitis. METHODS: Patients with uncomplicated acute bronchitis
      (bronchitis severity score [BSS] >= 5 score points) were randomly assigned to
      treatment with Spicae ae. or placebo in a double-blind, parallel-group design. No
      additional treatment was admitted. The primary objective was the mean difference
      of a defined total BSS of 25% between the Spicae ae. and the placebo group after
      7 days of full medication dose. Secondary endpoints included the BSS at day 10,
      additional signs and symptoms of bronchitis, quality of life (QoL) and safety.
      RESULTS: The mean decrease in BSS at day 7 and day 10 was significant with 4.79
      vs. 3.20 (p < 0.005 for a 25% difference) and 6.47 vs. 4.32 (p < 0.009 for a 25%
      difference) score points respectively in the Spicae ae. (n = 119) vs. placebo
      group (n = 110). Accordingly, most additional signs and symptoms of acute
      bronchitis as well as the patients' QoL improved significantly with Spicae ae. as
      compared to placebo. In all, 258 patients were eligible for safety analysis. The
      treatment with Spicae ae. was well tolerated; no serious adverse events occurred.
      CONCLUSION: The defined objectives both for the primary and secondary endpoints
      have been met. The results of this study provide evidence that Spicae ae. is well
      tolerated, effective and superior to placebo in the symptomatic treatment of
      uncomplicated acute bronchitis in adult patients.

PMID- 29209861
TI  - Development of new analytical methods for the determination of caffeine content
      in aqueous solution of green coffee beans.
AB  - BACKGROUND: This study was conducted to develop fast and cost effective methods
      for the determination of caffeine in green coffee beans. In the present work
      direct determination of caffeine in aqueous solution of green coffee bean was
      performed using FT-IR-ATR and fluorescence spectrophotometry. Caffeine was also
      directly determined in dimethylformamide solution using NIR spectroscopy with
      univariate calibration technique. RESULTS: The percentage of caffeine for the
      same sample of green coffee beans was determined using the three newly developed
      methods. The caffeine content of the green coffee beans was found to be 1.52 +/-
      0.09 (% w/w) using FT-IR-ATR, 1.50 +/- 0.14 (% w/w) using NIR and 1.50 +/- 0.05
      (% w/w) using fluorescence spectroscopy. The means of the three methods were
      compared by applying one way analysis of variance and at p = 0.05 significance
      level the means were not significantly different. The percentage of caffeine in
      the same sample of green coffee bean was also determined by using the literature
      reported UV/Vis spectrophotometric method for comparison and found to be 1.40 +/-
      0.02 (% w/w). CONCLUSION: New simple, rapid and inexpensive methods were
      developed for direct determination of caffeine content in aqueous solution of
      green coffee beans using FT-IR-ATR and fluorescence spectrophotometries. NIR
      spectrophotometry can also be used as alternative choice of caffeine
      determination using reduced amount of organic solvent (dimethylformamide) and
      univariate calibration technique. These analytical methods may therefore, be
      recommended for the rapid, simple, safe and cost effective determination of
      caffeine in green coffee beans.

PMID- 29209860
TI  - Identification of Inhibitory Compounds Against Singapore Grouper Iridovirus
      Infection by Cell Viability-Based Screening Assay and Droplet Digital PCR.
AB  - Singapore grouper iridovirus (SGIV) is one of the major causative agents of fish
      diseases and has caused significant economic losses in the aquaculture industry.
      There is currently no commercial vaccine or effective antiviral treatment against
      SGIV infection. Annually, an increasing number of small molecule compounds from
      various sources have been produced, and many are proved to be potential
      inhibitors against viruses. Here, a high-throughput in vitro cell viability-based
      screening assay was developed to identify antiviral compounds against SGIV using
      the luminescent-based CellTiter-Glo reagent in cultured grouper spleen cells by
      quantificational measurement of the cytopathic effects induced by SGIV infection.
      This assay was utilized to screen for potential SGIV inhibitors from five
      customized compounds which had been reported to be capable of inhibiting other
      viruses and 30 compounds isolated from various marine organisms, and three of
      them [ribavirin, harringtonine, and 2-hydroxytetradecanoic acid (2-HOM)] were
      identified to be effective on inhibiting SGIV infection, which was further
      confirmed with droplet digital PCR (ddPCR). In addition, the ddPCR results
      revealed that ribavirin and 2-HOM inhibited SGIV replication and entry in a dose
      dependent manner, and harringtonine could reduce SGIV replication rather than
      entry at the working concentration without significant toxicity. These findings
      provided an easy and reliable cell viability-based screening assay to identify
      compounds with anti-SGIV effect and a way of studying the anti-SGIV mechanism of
      compounds.

PMID- 29209862
TI  - Model selection criteria for dynamic brain PET studies.
AB  - BACKGROUND:  Several criteria exist to identify the optimal model for
      quantification of tracer kinetics. The purpose of this study was to evaluate the
      correspondence in kinetic model preference identification for brain PET studies
      among five model selection criteria: Akaike Information Criterion (AIC), AIC
      unbiased (AICC), model selection criterion (MSC), Schwartz Criterion (SC), and F
      test. MATERIALS AND METHODS: Six tracers were evaluated: [11C]FMZ, [11C]GMOM,
      [11C]PK11195, [11C]Raclopride, [18F]FDG, and [11C]PHT, including data from five
      subjects per tracer. Time activity curves (TACs) were analysed using six plasma
      input models: reversible single-tissue model (1T2k), irreversible two-tissue
      model (2T3k), and reversible two-tissue model (2T4k), all with and without blood
      volume fraction parameter (V B). For each tracer and criterion, the percentage of
      TACs preferring a certain model was calculated. RESULTS: For all radiotracers,
      strong agreement was seen across the model selection criteria. The F-test was
      considered as the reference, as it is a frequently used hypothesis test. The F
      test confirmed the AIC preferred model in 87% of all cases. The strongest (but
      minimal) disagreement across regional TACs was found when comparing AIC with
      AICC. Despite these regional discrepancies, same preferred kinetic model was
      obtained using all criteria, with an exception of one FMZ subject. CONCLUSION: In
      conclusion, all five model selection criteria resulted in similar conclusions
      with only minor differences that did not affect overall model selection.

PMID- 29209863
TI  - Patient-reported common symptoms as an assessment of interventions in medication
      reviews: a randomised, controlled trial.
AB  - Background A 'Patient-Reported Outcome Measure, Inquiry into Side Effects'
      (PROMISE) instrument was developed for patients to report common symptoms in
      clinical medication reviews. Objective To determine changes in patient-reported
      drug-associated symptoms collected by PROMISE before and after community
      pharmacist-led clinical medication reviews compared with usual care. Setting
      Community pharmacies in the Netherlands. Methods Patients were randomised into an
      intervention group (IG) and a control group (CG). PROMISE was used to collect
      symptoms experienced during the previous month, and any suspected drug-associated
      symptoms from both groups at baseline and at follow-up after 3 months. IG
      patients received a one-time clinical medication review, while CG patients
      received usual care. Main outcome measure Mean number of drug-associated symptoms
      at follow-up. Results Measurements were completed by 78 IG and 67 CG patients
      from 15 community pharmacies. Mean numbers of drug-associated symptoms per
      patient at follow-up were 4.0 in the IG and 5.0 in the CG, with an incident rate
      ratio between the groups of 0.90 (95% CI 0.62-1.33). Mean numbers of drug
      associated symptoms per patient reported at follow-up and persisting since
      baseline were 2.1 in the IG and 2.6 in the CG, with an incident rate ratio of
      0.85 (95% CI 0.43-1.42). The lowest percentages of persisting drug-associated
      symptoms detected in the IG were 'palpitations' and 'stomach pain, dyspepsia'
      while in the CG they were 'stomach pain, dyspepsia' and 'trembling, shivering'.
      Conclusion PROMISE provided meaningful information on drug-associated symptoms in
      clinical medication reviews, however the number of drug-associated symptoms was
      not reduced by performing clinical medication reviews compared with usual care.

PMID- 29209864
TI  - Pharmacists' and prescribers' neonatal abstinence syndrome (NAS) prevention
      behaviors: a preliminary analysis.
AB  - Background Maternal opioid use and neonatal abstinence syndrome (NAS) incidence
      have increased markedly in the US in recent years. Objectives (1) To assess
      prescribers' and community pharmacists' guideline-based NAS prevention behaviors;
      (2) to describe providers' perceptions of contraceptive appropriateness in female
      patients of childbearing age. Method Cross-sectional study of 100 randomly
      selected primary care physicians, 100 prescribers authorized to engage in in
      office treatment of opioid use disorders with buprenorphine, 100 pain management
      clinic directors, and 100 community pharmacists in Tennessee (N = 400 providers
      total) to evaluate self-reported engagement in 15 NAS prevention behaviors and
      perceived appropriateness of 8 contraceptive methods in opioid using women of
      childbearing age. Results An overall response rate of 17.5% was obtained. Pain
      clinic directors reported the most engagement in NAS prevention, engaging 80% or
      more of female patients of childbearing age prescribed an opioid in 11 prevention
      behaviors, followed by buprenorphine prescribers (8 behaviors), primary care
      physicians (5 behaviors), and community pharmacists (2 behaviors). Pain clinic
      directors, primary care physicians, and community pharmacists perceived oral
      contraceptive pills and patches to be as appropriate as long-acting, reversible
      forms of contraception (e.g., implants, injectable depots, intrauterine devices).
      Conclusion Provider engagement in behaviors that could prevent NAS is variable.
      Interventions should be implemented that equip providers to engage patients in
      conversations about long-acting, reversible contraception.

PMID- 29209865
TI  - Short and fast vs long and slow: age changes courtship in male orb-web spiders
      (Argiope keyserlingi).
AB  - Male reproductive performance can vary with condition, age and future
      reproductive opportunities. Web-building spiders are ideal models to examine the
      effects of senescence on fitness-related behaviours due to strong selection on
      male courtship to reduce pre-copulatory sexual cannibalism. Argiope keyserlingi
      spiders generate courtship vibrations, or 'shudders', that reduce female
      aggression. We found that male A. keyserlingi courtship slowed with chronological
      age. Older males took longer to travel across the courtship thread, and overall
      number of shudders increased. Males retained some ability to modulate courtship
      quality (shudder duration and number of rocks within each shudder) in response to
      female quality. A change in courtship performance over time, despite strong
      selection for repeatability, indicates that ageing in male A. keyserlingi may
      have direct impacts on reproductive performance.

PMID- 29209866
TI  - Photobiomodulation therapy protects skeletal muscle and improves muscular
      function of mdx mice in a dose-dependent manner through modulation of dystrophin.
AB  - This study aimed to analyze the protective effects of photobiomodulation therapy
      (PBMT) with combination of low-level laser therapy (LLLT) and light emitting
      diode therapy (LEDT) on skeletal muscle tissue to delay dystrophy progression in
      mdx mice (DMD mdx ). To this aim, mice were randomly divided into five different
      experimental groups: wild type (WT), placebo-control (DMD mdx ), PBMT with doses
      of 1 J (DMD mdx ), 3 J (DMD mdx ), and 10 J (DMD mdx ). PBMT was performed
      employing a cluster probe with 9 diodes (1 x 905nm super-pulsed laser diode; 4 x
      875nm infrared LEDs; and 4 x 640nm red LEDs, manufactured by Multi Radiance
      Medical(r), Solon - OH, USA), 3 times a week for 14 weeks. PBMT was applied on a
      single point (tibialis anterior muscle-bilaterally). We analyzed functional
      performance, muscle morphology, and gene and protein expression of dystrophin.
      PBMT with a 10 J dose significantly improved (p < 0.001) functional performance
      compared to all other experimental groups. Muscle morphology was improved by all
      PBMT doses, with better outcomes with the 3 and 10 J doses. Gene expression of
      dystrophin was significantly increased with 3 J (p < 0.01) and 10 J (p < 0.01)
      doses when compared to placebo-control group. Regarding protein expression of
      dystrophin, 3 J (p < 0.001) and 10 J (p < 0.05) doses also significantly showed
      increase compared to placebo-control group. We conclude that PBMT can mainly
      preserve muscle morphology and improve muscular function of mdx mice through
      modulation of gene and protein expression of dystrophin. Furthermore, since PBMT
      is a non-pharmacological treatment which does not present side effects and is
      easy to handle, it can be seen as a promising tool for treating Duchenne's
      muscular dystrophy.

PMID- 29209867
TI  - Non-specific effects and clusters of women with painful TMD responders and non
      responders to LLLT: double-blind randomized clinical trial.
AB  - The aim was to analyze the non-specific effects (placebo, spontaneous remission,
      and regression to the mean) of the low-level laser therapy (LLLT) in women with
      myofascial pain (painful temporomandibular disorder (TMD)), as well as to
      differentiate between responders and non-responder clusters to active and placebo
      LLLT according to the anxiety levels, salivary cortisol, use of oral
      contraceptives, and premenstrual period. Sixty-four women diagnosed with
      myofascial pain (Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD)) were included, divided into laser (n = 20), placebo group (n = 21),
      and 23 controls (without treatment (WT)). The LLLT applied was 780 nm, masseter
      and temporal = 5 J/cm2 (20 mW-0.5 W/cm2), and TMJ area = 7.5 J/cm2 (30 mW-0.8
      W/cm2), eight sessions, twice a week. The pain intensity (visual analogue scale
      (VAS)), anxiety (Beck Anxiety Inventory), salivary cortisol, and menstrual
      cycle's data at the baseline, T1-T8, and 30 days after LLLT (follow-up) were
      evaluated. The laser group showed 80% of pain reduction, placebo 85%, and WT 43%
      in T8. Women with severe anxiety and at the premenstrual period did not reduce
      pain with any LLLT. Active and placebo LLLT had similar effectiveness during the
      treatment period; however, women with moderate anxiety, cortisol levels above 10
      ng/ml, and without contraceptive use maintain analgesia longer with active LLLT
      than placebo (follow-up 30 days). Women with low levels of anxiety, salivary
      cortisol below 10 ng/ml, and with contraceptive use showed the higher pain
      reduction. The analgesia promoted by LLLT in women with myofascial pain is a
      result of non-specific effects during the treatment period, although active LLLT
      is more effective in maintaining the analgesia after treatment (30 days) for the
      cluster of women with moderate anxiety, salivary cortisol above 10 ng/ml, and
      without contraceptive use.

PMID- 29209869
TI  - Correction to: Effect of incubation duration, growth temperature, and abiotic
      surface type on cell surface properties, adhesion and pathogenicity of biofilm
      detached Staphylococcus aureus cells.
AB  - Following publication of the original article (Khelissa et al. 2017), the authors
      reported that the legend for Fig. 3 contained an error. Instead of "Adhesion of
      planktonic and biofilm-detached Staphylococcus aureus cells on stainless steel
      and polycarbonate. Cell cultures were grown at 20, 30 and 37  degrees C, during
      24 h (white square) and 48 h (white square). Planktonic cells adhesion on
      stainless steel (a) and polycarbonate (b). Adhesion of stainless steel-biofilm
      detached-cells on stainless steel 24 (c) and polycarbonate-biofilm-detached-cells
      on polycarbonate (d)", the legend should read "Adhesion of planktonic and biofilm
      detached Staphylococcus aureus cells on stainless steel and polycarbonate. Cell
      cultures were grown at 20, 30 and 37  degrees C, during 24 h (black square) and
      48 h (white square). Planktonic cells adhesion on stainless steel (a) and
      polycarbonate (b). Adhesion of stainless steel-biofilm-detached-cells on
      stainless steel 24

PMID- 29209868
TI  - Laser surface modification of decellularized extracellular cartilage matrix for
      cartilage tissue engineering.
AB  - The implantation of autologous cartilage as the gold standard operative procedure
      for the reconstruction of cartilage defects in the head and neck region
      unfortunately implicates a variety of negative effects at the donor site. Tissue
      engineered cartilage appears to be a promising alternative. However, due to the
      complex requirements, the optimal material is yet to be determined. As
      demonstrated previously, decellularized porcine cartilage (DECM) might be a good
      option to engineer vital cartilage. As the dense structure of DECM limits
      cellular infiltration, we investigated surface modifications of the scaffolds by
      carbon dioxide (CO2) and Er:YAG laser application to facilitate the migration of
      chondrocytes inside the scaffold. After laser treatment, the scaffolds were
      seeded with human nasal septal chondrocytes and analyzed with respect to cell
      migration and formation of new extracellular matrix proteins. Histology,
      immunohistochemistry, SEM, and TEM examination revealed an increase of the
      scaffolds' surface area with proliferation of cell numbers on the scaffolds for
      both laser types. The lack of cytotoxic effects was demonstrated by standard
      cytotoxicity testing. However, a thermal denaturation area seemed to hinder the
      migration of the chondrocytes inside the scaffolds, even more so after CO2 laser
      treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further
      modifications of the laser adjustments or the use of alternative laser systems
      might be advantageous for surface enlargement and to facilitate migration of
      chondrocytes into the scaffold in one step.

PMID- 29209870
TI  - Photosynthetic acclimation of Grammatophyllum speciosum to growth irradiance
      under natural conditions in Singapore.
AB  - Grammatophyllum speciosum, a native species to Singapore, have become extinct
      mainly due to habitat loss. Recently, Singapore has reintroduced G. speciosum
      into the natural environment under the orchid conservation programme. In this
      study, leaves of G. speciosum grown under low light (LL) under natural conditions
      had faster expansion rate and higher specific leaf area than leaves grown under
      intermediate light (IL) and high light (HL). All leaves had more than 95% midday
      relative water content. Although midday Fv/Fm ratios were lower in HL leaves than
      in IL and LL leaves, none of them exhibited chronic photoinhibition. HL leaves
      had upregulated their light utilization through higher photochemical quantum
      yield (DeltaF/Fm') and greater electron transport rate. HL leaves also had higher
      non-photochemical quenching, indicating that they had higher capability to
      dissipate excess light as heat, which was supported by their lower chlorophyll
      but higher carotenoids content. Although there was a linear correction between
      leaf temperature and photosynthetic photon flux density (PPFD), no correlations
      were found between stomatal conductance (gs) and PPFD, gs and leaf temperature.
      Light-saturated photosynthetic CO2 assimilation rate (A sat ) was significantly
      higher in HL leaves than those of IL and LL leaves. However, all leaves had
      similar light-saturated stomatal conductance. Although LL leaves had higher leaf
      total reduced nitrogen that those of IL and HL leaves, none of them seemed to
      suffer from nitrogen deficiency during the experimental period. To conclude, G.
      speciosum is able to survive under different growth irradiances without watering
      and adding fertilizers.

PMID- 29209871
TI  - Fe(II) reduction of pyrolusite (beta-MnO2) and secondary mineral evolution.
AB  - Iron (Fe) and manganese (Mn) are the two most common redox-active elements in the
      Earth's crust and are well known to influence mineral formation and dissolution,
      trace metal sequestration, and contaminant transformations in soils and
      sediments. Here, we characterized the reaction of aqueous Fe(II) with pyrolusite
      (beta-MnO2) using electron microscopy, X-ray diffraction, aqueous Fe and Mn
      analyses, and 57Fe Mossbauer spectroscopy. We reacted pyrolusite solids
      repeatedly with 3 mM Fe(II) at pH 7.5 to evaluate whether electron transfer
      occurs and to track the evolving reactivity of the Mn/Fe solids. We used Fe
      isotopes (56 and 57) in conjunction with 57Fe Mossbauer spectroscopy to isolate
      oxidation of Fe(II) by Fe(III) precipitates or pyrolusite. Using these
      complementary techniques, we determined that Fe(II) is initially oxidized by
      pyrolusite and that lepidocrocite is the dominant Fe oxidation product.
      Additional Fe(II) exposures result in an increasing proportion of magnetite on
      the pyrolusite surface. Over a series of nine 3 mM Fe(II) additions, Fe(II)
      continued to be oxidized by the Mn/Fe particles suggesting that Mn/Fe phases are
      not fully passivated and remain redox active even after extensive surface
      coverage by Fe(III) oxides. Interestingly, the initial Fe(III) oxide precipitates
      became further reduced as Fe(II) was added and additional Mn was released into
      solution suggesting that both the Fe oxide coating and underlying Mn phase
      continue to participate in redox reactions when freshly exposed to Fe(II). Our
      findings indicate that Fe and Mn chemistry is influenced by sustained reactions
      of Fe(II) with Mn/Fe oxides.

PMID- 29209872
TI  - Spectrobiopsy in neurodiagnostics: the new era.

PMID- 29209873
TI  - 99mTc-rituximab as a tracer for sentinel lymph node biopsy in breast cancer
      patients: a single-center analysis.
AB  - PURPOSE: This study aimed to determine the long-term prognosis of breast cancer
      patients with 99mTc-rituximab for sentinel lymph node biopsy (SLNB). METHODS: A
      total of 2947 patients with negative sentinel lymph nodes (SLNs) omitting
      axillary lymph node dissection (ALND), treated between June 2005 and December
      2013, were retrospectively analyzed. SLNB was performed prior to adjuvant
      therapy. RESULTS: After a median follow-up of 62 months, 22 cases of axillary
      recurrence (AR) were observed. The 5-year AR rate (ARR) was 0.7% [95% confidence
      interval (CI) 0.3-1.1%] and the 5-year relapse-free survival (RFS) was 95.2% (95%
      CI 94.4-96.0%). Multivariate analysis showed that abnormal axillary ultrasound
      with negative fine-needle aspiration (FNA) [hazard ratio (HR) 3.79, 95% CI 1.55
      9.28; P = 0.004], not receiving radiotherapy (HR 4.38, 95% CI 1.47-13.05; P =
      0.008), and age <= 40 years (HR 2.93, 95% CI 1.19-7.20; P = 0.020) were
      independent risk factors for AR. CONCLUSIONS: ARR of SLNB-negative patients with
      99mTc-rituximab is low. Abnormal axillary ultrasound with negative FNA, not
      receiving radiotherapy, and age <= 40 years were prognostic factors for higher
      ARRs.

PMID- 29209874
TI  - Utilization of hypofractionated radiotherapy in treatment of glioblastoma
      multiforme in elderly patients not receiving adjuvant chemoradiotherapy: A
      National Cancer Database Analysis.
AB  - To assess the utilization and outcomes of adjuvant monotherapy with
      hypofractionated radiation (RT) among elderly patients not receiving traditional
      adjuvant chemoradiotherapy (cRT) for glioblastoma multiforme (GBM). A
      retrospective analysis using the National Cancer Data Base with GBM patients aged
      65 years or older treated between 2005 and 2012 was conducted. Patients who
      underwent hypofractionated RT (40 Gy), conventional RT (60 Gy), chemotherapy, or
      best supportive care alone were included. Statistical methods included logistic
      regression for utilization and Cox regression for survival analysis. A total of
      9556 patients were analyzed. On multivariate analysis (compared to those
      receiving conventional RT), patients more likely to be treated with
      hypofractionated RT were older (75-84 years old OR 2.05; p < 0.01 and >= 85 years
      old OR 3.32; p < 0.01), with a Charlson/Deyo score of 2 or higher (OR 1.80; p =
      0.05), from communities > 50 miles from their treatment facility (50-100 miles OR
      8.03; p < 0.01 and > 100 miles OR 7.16; p < 0.01), treated at an
      Academic/Research facility (OR 2.85; p = 0.04), and diagnosed between 2011 and
      2012 (OR 4.15; p < 0.01). On Cox regression, hypofractionated RT (HR 0.65; p <
      0.01), conventional RT (HR 0.60; p < 0.01), and chemotherapy alone (HR 0.69; p <
      0.01) were all associated with decreased risk of death compared to no adjuvant
      therapy. Among patients receiving adjuvant treatment, utilization of
      hypofractionated RT increased from 7 to 19% during the study period. Among
      elderly patients with GBM not receiving cRT, the utilization of adjuvant
      monotherapy with hypofractionated RT has increased over time. Retrospective
      evidence suggests it may be better than best supportive care alone and as good as
      conventionally fractionated RT alone.

PMID- 29209875
TI  - Non-routine discharge disposition is associated with post-discharge complications
      and 30-day readmissions following craniotomy for brain tumor resection.
AB  - Several studies have reported an association between high-volume brain tumor
      centers and greater rates of routine discharge disposition in the context of
      better outcomes. However, the relationship between in-hospital complications,
      discharge destination, and postoperative adverse events (AEs) remains unexplored.
      The purpose of this study was thus to use a large, prospectively collected
      database to examine the association between discharge destination, post-discharge
      complications, readmissions, and reoperations among patients undergoing
      craniotomy for brain tumor. The 2011-2014 National Surgical Quality Improvement
      (NSQIP) database was employed to identify all adult patients who underwent a
      craniotomy for brain tumor resection. Demographics, comorbidities, and
      perioperative variables were collected for each patient. Univariate statistics
      with subsequent binary logistic regression analyses were used to explore the
      relationship between these perioperative factors and postoperative events,
      including major post-discharge complications, minor post-discharge AEs,
      readmissions, and return to the operating room (ROR). Significant variables such
      as demographics, comorbidities, operative time, body mass index, ASA
      classification and pre-discharge complications were controlled for in each model.
      Of the 14,854 patients identified, 11,409 (77.9%) were discharged home. After
      controlling for comorbidities and in-hospital AEs, discharge to skilled
      rehabilitation was an independent predictor of major post-discharge complications
      (OR 1.74, 95% CI 1.31-2.30, p < 0.001), minor post-discharge events (OR 1.60, 95%
      CI 1.07-2.41, p = 0.024), and ROR (OR 1.68, 95% CI 1.27-2.22, p < 0.001).
      Discharge to a care facility was predictive of major complications (OR 1.51, 95%
      CI 1.04-2.19, p = 0.030) and ROR (OR 2.02, 95% CI 1.46-2.80, p < 0.001). These
      factors may be considered in discharge planning and further outcomes studies for
      patients undergoing resection.

PMID- 29209876
TI  - Mentalization deficit in bipolar patients during an acute depressive and manic
      episode: association with cognitive functions.
AB  - BACKGROUND: A number of studies in bipolar patients have shown a deficit in
      mentalization (theory of mind), one of the main aspects of social cognition. The
      aim of current study was to assess both cognitive and affective mentalization in
      well-defined groups of depressed and manic bipolar patients, compared to healthy
      control subjects, using a battery of tests measuring mentalization processes. The
      second aim was to investigate a possible relationship between cognitive and
      affective mentalization and cognitive functions in bipolar patients during a
      depressive and manic episode. METHODS: The study involved 25 bipolar disorder
      type I patients (10 male, 15 female) during a depressive episode (mean 24 +/- 2
      points in the 17-item Hamilton Depression Rating Scale) and 25 patients (10 male,
      15 female) during a manic episode (mean 27 +/- 4 points in the Young Mania Rating
      Scale). The control group consisted of 25 healthy subjects (10 male, 15 female)
      without psychiatric disorders. To measure mentalization, a revised version of the
      Reading the Mind in the Eyes (R-MET), the Strange Stories (SS), the Faux Pas
      Recognition (FPR), and the Moving Shapes Paradigm (MSP) tests were used.
      Assessment of cognitive functioning was made using the Digit Span, Trail Making,
      and Wisconsin Card Sorting Tests. RESULTS: In bipolar patients significant
      deficits in both cognitive and affective mentalization were demonstrated during
      both acute depressive and manic episodes. The impairment in FPR in manic patients
      was more severe than that in the depressive ones. On the other hand, in MSP,
      manic patients showed significantly increased intentionality for non
      mentalization animations, compared with depressive patients and for "cause and
      effect" animations compared with control subjects. A significant relationship was
      found between the decrease in cognitive and affective mentalization and deficits
      of cognitive functions during both the depressive and manic episodes.
      CONCLUSIONS: The results obtained confirm the deficits of mentalization in
      bipolar I patients, during both acute depressive and manic episodes. We found
      that in such patients mentalization deficits significantly correlated with
      cognitive dysfunctions more so during depressive episodes.

PMID- 29209877
TI  - Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on
      Oral Dyskinesia in Rats.
AB  - Haloperidol is a widely used antipsychotic, despite the severe motor side effects
      associated with its chronic use. This study was carried out to compare oral
      dyskinesia induced by different formulations of haloperidol-loaded nanocapsules
      containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as
      core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules
      formulations were prepared, physicochemical characterized and administered (0.5
      mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and
      subchronically and after that cell viability and free radical generation in
      cortex and substantia nigra. All formulations presented satisfactory
      physicochemical parameters. Acutely, all formulations were able to prevent oral
      dyskinesia development in comparison to free haloperidol, except haloperidol
      loaded nanocapsules containing GSO, whose effect was only partial. After
      subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented
      oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules
      containing fish oil and GSO were more effective than caprylic/capric
      triglycerides nanocapsules and free haloperidol in cell viability preservation
      and control of free radical generation. Our findings showed that fish oil
      formulation may be considered as the best formulation of haloperidol-loaded lipid
      core nanocapsules, being able to prevent motor side effects associated with
      chronic use of antipsychotic drugs, as haloperidol.

PMID- 29209878
TI  - Cell-Type-Specific Spatiotemporal Expression of Creatine Biosynthetic Enzyme S
      adenosylmethionine:guanidinoacetate N-methyltransferase in Developing Mouse
      Brain.
AB  - Creatine is synthesized by S-adenosylmethionine:guanidinoacetate N
      methyltransferase (GAMT), and the creatine/phosphocreatine shuttle system
      mediated by creatine kinase (CK) is essential for storage and regeneration of
      high-energy phosphates in cells. Although the importance of this system in brain
      development is evidenced by the hereditary nature of creatine deficiency
      syndrome, the spatiotemporal cellular expression patterns of GAMT in developing
      brain remain unknown. Here we show that two waves of high GAMT expression occur
      in developing mouse brain. The first involves high expression in mitotic cells in
      the ventricular zone of the brain wall and the external granular layer of the
      cerebellum at the embryonic and neonatal stages. The second was initiated by
      striking up-regulation of GAMT in oligodendrocytes during the second and third
      postnatal weeks (i.e., the active myelination stage), which continued to
      adulthood. Distinct temporal patterns were also evident in other cell types. GAMT
      was highly expressed in perivascular pericytes and smooth muscle cells after
      birth, but not in adults. In neurons, GAMT levels were low to moderate in
      neuroblasts residing in the ventricular zone, increased during the second
      postnatal week when active dendritogenesis and synaptogenesis occur, and
      decreased to very low levels thereafter. Moderate levels were observed in
      astrocytes throughout development. The highly regulated, cell type-dependent
      expression of GAMT suggests that local creatine biosynthesis plays critical roles
      in certain phases of neural development. In accordance with this idea, we
      observed increased CK expression in differentiating neurons; this would increase
      creatine/phosphocreatine shuttle system activity, which might reflect increased
      energy demand.

PMID- 29209880
TI  - Efficacy of locally produced Latanoprost in the control of intraocular pressure
      in patients with primary open-angle glaucoma.
AB  - PURPOSE: To determine the efficacy of locally produced Latanoprost in reducing
      the intraocular pressure (IOP) in patients with Primary open-angle glaucoma
      (POAG). DESIGN: Open-label, non-comparative, observational case study with non
      probability purposive sampling. METHODS: A total of 48 patients (94 eyes) of
      either gender were recruited from glaucoma clinic with the diagnosis of POAG,
      having IOP of more than 21 mmHg. Patients were commenced on locally produced
      Latanoprost (Vislat 0.005%). IOP was subsequently measured at 4 weeks and 12
      weeks, respectively. The primary end point was reduction in IOP at 12 weeks after
      the initiation of treatment. RESULTS: A total of 48 patients (94 eyes) were
      recruited from glaucoma clinic. The average IOP of our patients at baseline was
      28.6 +/- 8.1 mmHg, decreasing to 21.3 +/- 10.6 mmHg at 4 weeks, indicating a drop
      of 19.1% (P < 0.001). IOP further decreased to 20.3 +/- 8.7 mmHg after 3 months
      of treatment indicating a decrease of 23.3% (P < 0.001). A decrease in IOP
      occurred in 51 eyes (71.8%) at 4 weeks after treatment, improving to 54 eyes
      (76%) at 3-month follow-up. Twenty eyes (28.1%) did not show any change in IOP at
      4 weeks. However, after 3-month follow-up only 17 eyes (23.9%) did not reveal any
      change in IOP. CONCLUSION: Our results showed a decrease in IOP of 19.1% after 4
      weeks, increasing to 23.3% at 12 weeks in cohort of 37 patients (72 eyes) treated
      with locally produced Latanoprost (Vislat 0.005%).

PMID- 29209879
TI  - One-pot analysis of sulfated glycosaminoglycans.
AB  - Routine isolation, estimation, and characterization of glycosaminoglycans (GAGs)
      is quite challenging. This is compounded by the fact that the analysis is
      technique-intensive and more often there will be a limitation on the quantity of
      GAGs available for various structural, functional and biological studies. In such
      a scenario, the sample which can be made available for estimation and elucidation
      of disaccharide composition and species composition as well remains a challenge.
      In the present study, we have determined the feasibility where isolated sulfated
      GAGs (sGAG) that is estimated by metachromasia is recovered for further analysis.
      sGAG-DMMB complex formed after estimation of sGAG by DMMB dye-binding assay was
      decomplexed and sGAGs were recovered. Recovered sGAGs were analysed by cellulose
      acetate membrane electrophoresis and taken up for disaccharide composition
      analysis by HPLC after fluorescent labelling. Good recovery of sGAGs after
      metachromasia was observed in all samples of varying levels of purity by this
      protocol. Further analysis using cellulose acetate membrane electrophoresis
      showed good separation between species of sGAGs namely chondroitin/dermatan
      sulfate and heparan sulfate, with comparatively lesser interference from
      hyaluronic acid, a non-sulfated GAG. Analysis of recovered sGAGs, specifically
      heparan sulfate by HPLC showed characteristic disaccharide composition akin to
      that of GAG obtained by the conventional protocol. Thus, in the present paper, we
      show that sGAG can be recovered in comparatively purer form after routine
      estimation and can be used for further analysis thus saving up on the precious
      sample.

PMID- 29209881
TI  - The costs of repatriating an ill seafarer: a micro-costing approach.
AB  - Seafarers sail the high seas around the globe. In case of illness, they are
      protected by international regulations stating that the employers must pay all
      expenses in relation to repatriation, but very little is known about the cost of
      these repatriations. The objective of this study was to estimate the financial
      burden of repatriations in case of illness. We applied a local approach, a micro
      costing method, with an employer perspective using four case vignettes: I) Acute
      myocardial infarction (AMI), II) Malignant hypertension, III) Appendicitis and
      IV) Malaria. Direct cost data were derived from the Danish Maritime Authority
      while for indirect costs estimations were applied using the friction cost
      approach. The average total costs of repatriation varied for the four case
      vignettes; AMI (98,823 EUR), Malignant hypertension (47,597 EUR), Appendicitis
      (58,639 EUR) and Malaria (23,792 EUR) mainly due to large variations in the
      average direct costs which ranged between 9560 euro in the malaria case and
      77,255 in the AMI case. Repatriating an ill seafarer is a costly operation and
      employers have a financial interest in promoting the health of seafarers by
      introducing or further strengthen cost-effective prevention programs and hereby
      reducing the number of repatriations.

PMID- 29209882
TI  - Hemodynamics of Focal Versus Global Growth of Small Cerebral Aneurysms.
AB  - BACKGROUND AND PURPOSE: Hemodynamics play a driving role in the life cycle of
      brain aneurysms from initiation through growth until eventual rupture. The
      specific factors behind aneurysm growth, especially in small aneurysms, are not
      well elucidated. The goal of this study was to differentiate focal versus general
      growth and to analyze the hemodynamic microenvironment at the sites of
      enlargement in small cerebral aneurysms. MATERIALS AND METHODS: Small aneurysms
      showing growth during follow-up were identified from our prospective aneurysm
      database. Three dimensional rotational angiography (3DRA) studies before and
      after morphology changes were available for all aneurysms included in the study,
      allowing for detailed shape and computational fluid dynamic (CFD) based
      hemodynamic analysis. Six patients fulfilled the inclusion criteria. RESULTS: Two
      different types of change were observed: focal growth, with bleb or blister
      formation in three, and global aneurysm enlargement accompanied by neck
      broadening in other three patients. Areas of focal growth showed low shear
      conditions with increased oscillations at the site of growth (a low wall shear
      stress [WSS] and high oscillatory shear index [OSI]). Global aneurysm enlargement
      was associated with increased WSS coupled with a high spatial wall shear stress
      gradient (WSSG). CONCLUSION: For different aneurysm growth types, distinctive
      hemodynamic microenvironment may be responsible and temporal-spatial changes of
      the pathologic WSS would have the inciting effect. We suggest the distinction of
      focal and global growth types in future hemodynamic and histological studies.

PMID- 29209883
TI  - Disseminated juvenile xanthogranuloma occurring after treatment of Langerhans
      cell histiocytosis: a case report.
AB  - CASE PRESENTATION: An 11-year-old boy presented with a complaint of a painful
      temporal mass. Brain magnetic resonance imaging (MRI) showed a 3-cm-sized,
      homogeneously enhancing mass in the greater wing of the left sphenoid bone, which
      was diagnosed as Langerhans cell histiocytosis (LCH). Chemotherapy with
      vincristine and prednisolone was performed for 1 year. After 1 year and 11 months
      off treatment, he developed symptoms such as polydipsia and polyuria. Brain MRI
      showed thickening of the pituitary stalk with enhancement, suggestive of LCH
      involvement, and no recurrence in the sphenoid bone. After 4 years and 4 months
      off treatment, he developed multiple, subcutaneous, asymptomatic, and yellowish
      variable-sized papules on his face, posterior neck, and back, which were
      pathologically diagnosed as juvenile xanthogranuloma (JXG). Brain MRI revealed
      multifocal enhancing skull lesions in the left parietal, right frontal, and left
      occipital bones, which were also diagnosed as JXG. After 5 years and 8 months off
      treatment, the number of variable-sized skin lesions was increased without
      changes in the lesions in the skull and pituitary stalk. CONCLUSION: We report a
      case of disseminated JXG occurring after treatment of LCH. These clinical co
      presentations suggested a close relationship between their pathogenesis.

PMID- 29209884
TI  - Congenital obstruction of foramen of Monro: report of 10 patients and literature
      review.
AB  - INTRODUCTION: A wide spectrum of etiologies can obstruct foramen of Monro (FOM)
      and result in hydrocephalus. Congenital occlusion of FOM is a rare entity which
      may present either in childhood or in adulthood. METHODS: Between 2007 and 2016,
      we screened all pediatric patients with hydrocephalus of either one or both
      lateral ventricles. Congenital occlusion of FOM was confirmed in the absence of
      masses occupying the FOM, prenatal or postnatal central nervous system (CNS)
      infections, intraventricular hemorrhage, previous cerebral intervention, or
      associated CNS anomalies affecting the flow of cerebrospinal fluid (CSF). We have
      performed a comprehensive literature review of the previously reported cases and
      provided a tentative embryological pathogenesis of FOM occlusion. RESULTS: We
      introduce 10 new cases of congenital FOM obstruction. The mean age of the
      patients was 6.65 +/- 10.51 months. Two patients underwent ventriculo-peritoneal
      (VP) shunting as the primary intervention, while endoscopic septostomy was
      performed in the others. The mean follow-up was 3.05 +/- 2.16 years (1-8 years).
      Although the hydrocephalus was controlled, all patients remained hemiparetic with
      some degree of developmental and cognitive impairments. Previously, 38 similar
      cases were reported: 10 of them (26.3%) were adults. Overall, VP shunting was the
      treatment of choice in 44.7% of patients. While most adults fully recovered, 7.2%
      of pediatrics remained hemiparetic and 10.7% of them had cognitive and
      developmental delay. CONCLUSION: Ten cases of congenital obstruction of the
      foramen of Monro have been managed through a period of 9-year study. Details of
      these patients in addition to 38 previously reported cases are presented in this
      study.

PMID- 29209885
TI  - Neuroimaging findings associated with congenital Zika virus syndrome: case series
      at the time of first epidemic outbreak in Pernambuco State, Brazil.
AB  - PURPOSE: This study aimed to describe the prenatal and postnatal neuroimaging and
      clinical findings in a clinical series following congenital Zika virus syndrome
      during the first epidemic Zika virus (ZIKV) outbreak in the State of Pernambuco,
      Brazil. METHODS: We (the authors) conducted a retrospective study of a
      prospectively collected case series of fetuses and neonates with microcephaly
      born to mothers with presumed/confirmed congenital ZIKV syndrome. Prenatal
      ultrasound findings were reviewed to identify potential central nervous system
      (CNS) abnormalities. Neonates underwent postnatal neuroimaging follow up by
      computed tomography (CT)-scan or magnetic resonance (MR) imaging. RESULTS: The
      prenatal and postnatal outcomes of eight fetuses/neonates born to mothers with
      presumed/confirmed congenital ZIKV syndrome were examined. The mean gestational
      age at ultrasound was 31.3 weeks. Severe microcephaly was identified in seven
      fetuses (87.5%), while ventriculomegaly and brain calcifications were detected in
      all fetuses. The mean gestational age at delivery and head circumference were 38
      weeks and 30.2 cm, respectively. All cases of microcephaly but one was confirmed
      postnatally. Brain CT scans or MRIs were performed in seven newborns, and all had
      periventricular and/or parenchymal calcifications, symmetrical or asymmetrical
      ventriculomegaly, pachygyria, and reduced sulcation and gyration. MR imaging
      aided the detection of one undetected case of corpus callosum dysgenesis and was
      essential in documenting reduced mantel of the cerebral cortex and reduced
      gyration and sulcation, especially involving the parietal lobe. In addition, MR
      imaging was also able to display irregular interfaces with the subcortical white
      matter, a finding consistent with polymicrogyria, more frequently seen at the
      level of the frontal lobe and atrophic and thinned pons. CONCLUSION: Severe
      microcephaly and CNS abnormalities may be associated with congenital ZIKV
      syndrome.

PMID- 29209886
TI  - Reply to the letter by Joob and Wiwanitkit regarding our article on congenital
      Zika syndrome and hydrocephalus.

PMID- 29209887
TI  - The relationship between hematological parameters and prognosis of children with
      acute ischemic stroke.
AB  - BACKGROUND: Stroke is rarely seen in children, but it is a major cause of
      morbidity and mortality. Therefore, there is a need for inexpensive and
      noninvasive diagnostic methods for estimating the prognosis. Although the
      prognostic importance of hematological parameters in acute ischemic stroke were
      reported in adult studies, there is a lack in pediatric ages. The aim of the
      study is to investigate the relationship between hematological parameters and
      prognosis of acute ischemic stroke in children. METHODS: Retrospectively scanned
      in the study were 106 pediatric patients with acute ischemic stroke who managed
      at the Medical Faculty of Erciyes University, Kayseri, between the years of 2000
      and 2014. White blood count (WBC); neutrophil, lymphocyte, and platelet count;
      mean platelet volume (MPV); platelet distribution width (PDW); neutrophil
      count/lymphocyte count (N/L) ratio values obtained from the measurements and
      initial symptoms; demographical features; risk factors; neurological examination;
      and clinical follow-up were recorded. Their hematological parameters were
      compared with those of 106 age and sex-matched healthy individuals. RESULTS: MPV
      and PDW values were found similar in patient and control groups, and the platelet
      count was found significantly low in the control group (p = 0,028). WBC,
      neutrophil count, and N/L ratio were found considerably high in the patient group
      (p < 0.001). Lymphocyte count, however, was found significantly low in the
      control group (p < 0.001). No statistically significant difference was detected
      in WBC, neutrophil count, lymphocyte count, platelet count, N/L ratio, and MPV
      and PDW values between the group with sequelae and the one without sequelae. In
      addition, it was determined that WBC, neutrophil count, lymphocyte count,
      platelet count, N/L ratio, and MPV and PDW values in the univariate Cox
      regression analysis of the patient group had no effect on survival and disease
      free survival. When receiver operating characteristic curve was applied, it was
      observed that the area below WBC, N/L ratio curve was important in the patient
      group in terms of predicting acute ischemic stroke. CONCLUSION: The values of
      WBC, neutrophil count, and N/L ratio differ significantly from those of the
      control group. The WBC and N/L ratio may help for an earlier diagnosis in
      children with acute ischemic stroke. WBC, thrombocyte count, MPV, PDW, and N/L
      ratio do not constitute a risk in overall survival, disease-free survival, and
      sequelae development.

PMID- 29209889
TI  - Fusarium head blight incidence and mycotoxin accumulation in three durum wheat
      cultivars in relation to sowing date and density.
AB  - Durum wheat (Triticum turgidum var. durum) is an important crop in Europe,
      particularly in the Mediterranean countries. Fusarium head blight (FHB) is
      considered as one of the most damaging diseases, resulting in yield and quality
      reduction as well as contamination of grain with mycotoxins. Three winter durum
      wheat cultivars originating from Austria, Slovakia, and Poland were analyzed
      during 2012-2014 seasons for FHB incidence and Fusarium mycotoxin accumulation in
      harvested grain. Moreover, the effects of sowing density and delayed sowing date
      were evaluated in the climatic conditions of Southern Poland. Low disease
      severity was observed in 2011/2012 in all durum wheat cultivars analyzed, and
      high FHB occurrence was recorded in 2012/2013 and 2013/2014 seasons. Fusarium
      graminearum was the most abundant pathogen, followed by Fusarium avenaceum.
      Through all three seasons, cultivar Komnata was the most susceptible to FHB and
      to mycotoxin accumulation, while cultivars Auradur and IS Pentadur showed less
      symptoms. High susceptibility of cv. Komnata was reflected by the number of
      Fusarium isolates and elevated mycotoxin (deoxynivalenol, zearalenone, and
      moniliformin) content in the grain of this cultivar across all three seasons.
      Nivalenol was identified in the samples of cv. Komnata only. Genotype-dependent
      differences in FHB susceptibility were observed for the plants sown at optimal
      date but not at delayed sowing date. It can be hypothesized that cultivars bred
      in Austria and Slovakia show less susceptibility towards FHB than the cultivar
      from Poland because of the environmental conditions allowing for more efficient
      selection of breeding materials.

PMID- 29209890
TI  - A Longitudinal Assessment of Associations Between Women's Tendency to Pretend
      Orgasm, Orgasm Function, and Intercourse-Related Pain in Different Partner
      Relationship Constellations.
AB  - The aim of the present study was to investigate how women's tendency to pretend
      orgasm during intercourse is associated with orgasm function and intercourse
      related pain, using a longitudinal design where temporal stability and possible
      causal relationships could be modeled. The study sample consisted of 1421 Finnish
      women who had participated in large-scale population-based data collections
      conducted at two time points 7 years apart. Pretending orgasm was assessed for
      the past 4 weeks, and orgasm function and pain were assessed using the Female
      Sexual Function Index for the past 4 weeks. Associations were also computed
      separately in three groups of women based on relationship status. Pretending
      orgasm was considerably variable over time, with 34% of the women having
      pretended orgasm a few times or more at least at one time point, and 11% having
      done so at both time points. Initial bivariate correlations revealed associations
      between pretending orgasm and orgasm problems within and across time, whereas
      associations with pain were more ambiguous. However, we found no support in the
      path model for the leading hypotheses that pretending orgasms would predict pain
      or orgasm problems over a long period of time, or that pain or orgasm problems
      would predict pretending orgasm. The strongest predictor of future pretending in
      our model was previous pretending (R 2 = .14). Relationship status did not seem
      to affect pretending orgasm in any major way.

PMID- 29209892
TI  - Erratum to: N-Terminal seven-amino-acid extension simultaneously improves the pH
      stability, optimal temperature, thermostability and catalytic efficiency of
      chitosanase CsnA.
AB  - In Table 1 as published, some of the data were wrong. The corrected Table 1 is
      shown below.

PMID- 29209891
TI  - Renal response to anaphylaxis in anesthetized rats and isolated perfused rat
      kidneys: roles of nitric oxide.
AB  - We determined the renal responses to anaphylaxis and the effects of a nitric
      oxide synthesis inhibitor, L-NAME, in anesthetized rats and isolated perfused rat
      kidneys. After the ovalbumin antigen injection, the sensitized rats showed
      transient and substantial decreases in mean blood pressure and renal blood flow
      and an increase in renal vascular resistance. Creatinine clearance, a measure of
      renal function, decreased to 53% baseline at 2 h after antigen. L-NAME
      pretreatment significantly enhanced the antigen-induced renal vasoconstriction
      and renal dysfunction. Moreover, plasma creatinine levels significantly increased
      only in the L-NAME pretreated rats. Separately, in isolated perfused kidneys, we
      observed the antigen-induced renal vasoconstriction and its augmentation by L
      NAME. In conclusion, the renal vascular response to the antigen is
      vasoconstriction, which is enhanced by L-NAME in both isolated perfused rat
      kidneys and anesthetized rats; it is accompanied by renal dysfunction, which is
      also augmented by L-NAME.

PMID- 29209893
TI  - Immobilization of enzymes using a multifunctional fusion polypeptide.
AB  - OBJECTIVE: To design a fusion polypeptide combining functions of self-assembly
      and purification for immobilizing enzymes. RESULTS: A collagen-like polypeptide
      (CLP) was fused to an elastin-like polypeptide (ELP) through genetic engineering.
      CLP-ELP was separately fused to superoxide dismutase (SOD) and D-amino acid
      oxidase (DAAO). The recombinant enzymes were purified with using reversible phase
      transition. The interfering effect of H2O2 on the secondary structures of the
      recombinant enzymes was significantly reduced. The stability of the recombinant
      enzymes against denaturing by urea was improved. SOD-CLP-ELP exhibited a
      proteinaceous microporous network, and DAAO-CLP-ELP exhibited micro-clusters. The
      superoxide anion (*O2-) scavenging ability of SOD-CLP-ELP was 1.5 times that of
      SOD, and the catalytic efficiency of DAAO-CLP-ELP was 1.7 times that of DAAO.
      CONCLUSIONS: The advantages of the CLP-ELP-fused enzymes have been demonstrated
      and CLP-ELP can be used to immobilize other enzymes/proteins.

PMID- 29209894
TI  - Mitochondrial energy metabolism and signalling in human glioblastoma cell lines
      with different PTEN gene status.
AB  - Glioblastomas epidemiology and aggressiveness demand for a well characterization
      of biochemical mechanisms of the cells. The discovery of oxidative tumours
      related to chemoresistance is changing the prevalent view of dysfunctional
      mitochondria in cancer cells. Thus, glioblastomas metabolism is now an area of
      intense research, wherein was documented a high heterogeneity in energy
      metabolism and in particular in mitochondrial OxPhos. We report results gained by
      investigating mitochondrial OxPhos and bioenergetics, in a model of three human
      glioblastoma cell lines characterized by a different PTEN gene status. Functional
      data are analysed in relation to the expression levels of some main transcription
      factors and signalling proteins, which can be involved in the regulation of
      mitochondrial biogenesis and activity. Collectively, our observations indicate
      for the three cell lines a similar bioenergetic phenotype maintaining a certain
      degree of mitochondrial oxidative activity, with some difference for PTEN-wild
      type SF767 cells respect to PTEN-deleted A172 and U87MG characterized by a loss
      of-function point mutation of PTEN. SF767 has lower ATP content and higher
      ADP/ATP ratio, higher AMPK activating-phosphorylation evoking energy impairment,
      higher OxPhos complexes and PGC1alpha-Sirt3-p53 protein abundance, in line with a
      higher respiration. Finally, SF767 shows a similar mitochondrial energy supply,
      but higher non-phosphorylating respiration linked to dissipation of protonmotive
      force. Intriguingly, it is now widely accepted that a regulated mitochondrial
      proton leak attenuate ROS generation and in tumours may be at the base of pro
      survival advantage and chemoresistance.

PMID- 29209895
TI  - Antiviral activity and metal ion-binding properties of some 2-hydroxy-3
      methoxyphenyl acylhydrazones.
AB  - Here we report on the results obtained from an antiviral screening, including
      herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4
      virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta
      Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three
      cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma
      cells, and African Green monkey kidney cells). Interesting antiviral EC50 values
      are obtained against herpes simplex virus-1 and vaccinia virus. The biological
      activity of acylhydrazones is often attributed to their metal coordinating
      abilities, so potentiometric and microcalorimetric studies are here discussed to
      unravel the behavior of the three 2-hydroxy-3-methoxyphenyl compounds in
      solution. It is worth of note that the acylhydrazone with the higher affinity for
      Cu(II) ions shows the best antiviral activity against herpes simplex and vaccinia
      virus (EC50 ~ 1.5 uM, minimal cytotoxic concentration = 60 uM, selectivity index
      = 40).

PMID- 29209896
TI  - BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone
      Signaling in the Progression of Papillary Thyroid Carcinoma.
AB  - Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence
      triggered by the action of oncogenes. It is a mechanism adopted by a cell to
      inhibit progression of benign tumors into malignancy, occurs in premalignant
      lesions, and is almost never present in malignant lesions. BRAF mutations occur
      in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is
      the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the
      upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte
      membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo
      cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A
      simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to
      hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis)
      would cause senescent tumor cells to overcome OIS and proceed towards malignancy,
      hence showing the importance of TSH/TSHR signaling in the development of PTCs.
      Increase in TSH/TSHR signaling triggers an increase in levels of downstream
      enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific
      phosphatase 6 (DUSP6) which eventually results in the production of oncogenic
      proteins such as c-Myc. Therefore, the detection of these genetic alterations as
      effective biomarkers for premalignant lesions of PTC is important in clinical
      settings and techniques such as polymerase chain reaction-mediated restriction
      fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect
      the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6,
      respectively.

PMID- 29209897
TI  - Adaptation of couples living with a high risk of breast/ovarian cancer and the
      association with risk-reducing surgery.
AB  - Women who carry BRCA1/2 mutations have a significantly elevated risk for breast
      and ovarian cancer. The positive test result and subsequent decisions about risk
      reducing behaviors can evoke distress, anxiety and worry. Psychological
      adaptation, or the process of coming to terms with the implications of a health
      threat, is an understudied construct in BRCA1/2 carriers. Little is known about
      adaptation and how it relates to other aspects of living at high risk for cancer.
      Even less is understood about adaptation among partners of BRCA1/2 carriers, and
      its relationship to adaptation in high risk individuals. Women at increased risk
      of breast/ovarian cancer (N = 103) and a subset of partners (N = 39) completed
      questionnaires that assessed risk management decisions (e.g. screening, risk
      reducing surgery), dyadic coping, and the outcome of psychological adaptation.
      Women who had undergone risk-reducing mastectomy (RRM) had significantly higher
      levels of adaptation than those who had not (t = 5.5, p < 0.001, d = 1.10).
      Partners of women who had undergone RRM also had higher levels of adaptation than
      partners of women who had not undergone RRM (t = 3.7, p = 0.01, d = 0.96), though
      this association was not statistically significant when controlling for carriers'
      adaptation. Undergoing risk-reducing oophorectomy was not associated with
      adaptation for BRCA1/2 carriers or their partners. Risk-reducing mastectomy is a
      significant event in the process of adapting to life at risk for hereditary
      cancer. Further, adaptation among partners is highly related to adaptation in
      carriers. These results aid in the understanding of the experience of couples
      living with cancer risk and the medical decisions related to adaptation.

PMID- 29209898
TI  - Clinical application of next generation sequencing in hereditary spinocerebellar
      ataxia: increasing the diagnostic yield and broadening the ataxia-spasticity
      spectrum. A retrospective analysis.
AB  - One of the hardest challenges in medical genetics is to reach a molecular
      diagnosis in the presence of rare brain disorders. Hereditary spinocerebellar
      ataxia (HA), characterized by high clinical and genetic heterogeneity, is among
      the diseases that present this challenge. HA can have features overlapping with
      those of other neurological diseases, especially hereditary spastic paraplegia
      (HSP), as routine clinical application of next generation sequencing (NGS) has
      confirmed. This article reviews different NGS methods applied in heterogeneous
      cohorts of patients with suspected HA and suggests that exome sequencing should
      be considered the first-tier genetic approach in this setting. Its application
      lends support to the hypothesis of HA and HSP as two extremes of a continuous
      spectrum.

PMID- 29209899
TI  - When Behavioral Health Concerns Present in Pediatric Primary Care: Factors
      Influencing Provider Decision-Making.
AB  - Primary care providers (PCPs) frequently encounter behavioral health (BH) needs
      among their pediatric patients. However, PCPs report variable training in and
      comfort with BH, and questions remain about how and when PCPs address pediatric
      BH needs. Existing literature on PCP decisions to address pediatric BH in-office
      versus referring to subspecialty BH is limited and findings are mixed.
      Accordingly, this study sought to examine parameters and contextual factors
      influencing PCP decisions and practices related to BH care. Qualitative interview
      results with 21 PCPs in Maryland indicated that decisions about how and when to
      address pediatric BH concerns are influenced by the type BH service needed,
      patient characteristics, the availability of BH services in the community, and
      possibly PCPs' perceptions of BH care as a distinct subspecialty. Findings
      suggest that efforts to support individual PCPs' capacity to address BH within
      primary care must be balanced by efforts to expand the subspecialty BH workforce.

PMID- 29209900
TI  - Effect of Testosterone on TRPV1 Expression in a Model of Orofacial Myositis Pain
      in the Rat.
AB  - Recent clinical studies have revealed sex differences in response to transient
      receptor potential vanilloid 1 (TRPV1) agonist-induced pain. However, the
      mechanism of these differences in TRPV1-related chronic pain remains unclear. In
      the present study, we investigate the effects of inflammation and gonadal
      hormones on TRPV1 expression in trigeminal ganglia. Inflammatory pain was modeled
      by injecting complete Freund's adjuvant (CFA) into the left masseter muscle in
      rats. TRPV1 mRNA and protein levels in the trigeminal ganglia of male and female
      rats following CFA injection were assessed. CFA-induced changes in TRPV1 mRNA and
      protein expression in the trigeminal ganglia from orchidectomized (ODX) male rats
      and testosterone-replaced ODX rats were examined. Additionally, TRPV1 mRNA levels
      in the trigeminal ganglia from ovariectomized (OVX) female and ODX male rats
      treated with tamoxifen were assessed. We found that the levels of TRPV1 mRNA and
      protein in the trigeminal ganglia from female rats following CFA injection were
      significantly higher than in the ganglia from naive female rats. CFA-induced
      inflammatory hyperalgesia did not alter TRPV1 expression in the trigeminal
      ganglia from male rats. The TRPV1 mRNA and protein expression levels in the ODX
      male trigeminal ganglia were significantly upregulated on day 3 following the
      initiation of inflammation. However, CFA-induced inflammatory pain had no
      significant effect on TRPV1 mRNA or protein expression in testosterone-replaced
      ODX rats. Furthermore, tamoxifen was unable to inhibit the upregulation of TRPV1
      expression in OVX female and ODX male rats after CFA injection. In summary, these
      data indicate that gender differences in TRPV1 function may be, in part, mediated
      by sex-dependent TRPV1 expression in sensory ganglia. Testosterone plays a key
      role in the inhibition of TRPV1 expression in this rat chronic inflammatory pain
      model.

PMID- 29209901
TI  - Abundant Focal Adhesion Kinase Causes Aberrant Neuronal Migration Via Its
      Phosphorylation at Tyr925.
AB  - The process of neuronal migration is precisely regulated by different molecules
      during corticogenesis. The FAK (focal adhesion kinase) plays a critical role in
      embryogenesis and is involved in cell motility through focal adhesions, but the
      underlying mechanisms on inordinate expression are unclear. To investigate the
      effect of FAK overexpression on neuronal migration spatiotemporally, mice FAK was
      transfected into the neurons in vivo by electroporation. Results showed that
      exogenous FAK distributed in the cytoplasm (in vivo) and co-localized with
      vinculin (in vitro) and induced aberrant neuronal migration via phosphorylation
      of FAK at Tyr925 during cerebral cortex development. Meanwhile, FAK Y925F mutant
      also induced aberrant neuronal migration like inordinate FAK/GFP phenotype. All
      these results implied that FAK-induced abnormal phenotype depended on
      phosphorylation of FAK at Tyr925, and this demonstrated that the overexpression
      of FAK impaired neuronal migration through its phosphorylation and activity of
      FAK during corticogenesis.

PMID- 29209902
TI  - Dehydropropylpantothenamide isolated by a co-culture of Nocardia tenerifensis IFM
      10554T in the presence of animal cells.
AB  - A new amide, named dehydropropylpantothenamide (1), was obtained by a co-culture
      of Nocardia tenerifensis IFM 10554T in the presence of the mouse macrophage-like
      cell line J774.1 in modified Czapek-Dox (mCD) medium. Compound 1 was synthesized
      from D-pantothenic acid calcium salt in 6 steps. The absolute configuration of
      natural compound 1 was determined by comparisons of the optical rotation and CD
      spectra of synthetic 1. In the present study, a new method for producing
      secondary metabolites was demonstrated using a "co-culture" in which the genus
      Nocardia was cultured in the presence of an animal cell line.

PMID- 29209903
TI  - Influence of a Co-culture of Streptococcus thermophilus and Lactobacillus casei
      on the Proteolysis and ACE-Inhibitory Activity of a Beverage Based on
      Reconstituted Goat Whey Powder.
AB  - The potential for reusability of whey is of concern due to its substantial
      nutritional value and, second, in view of the need to reduce environmental
      impact. The use of goat whey powder in the production of a fermented dairy
      beverage using a Lactobacillus casei culture as adjunct shows a good prospect of
      a food product with hypotensive activity. This study investigated the microbial
      viability, proteolysis and angiotensin-converting enzyme (ACE) inhibitory
      activity of a fermented dairy beverage produced with goat whey powder and a
      probiotic culture of L. casei BGP93 co-cultured with Streptococcus thermophilus
      TA-40. The probiotic beverage exhibited no significant difference from the
      control (absence of L. casei) with regard to titratable acidity, S. thermophilus
      viability and proteolysis degree during 21 days of storage (P > 0.05). During
      this period, the beverage maintained L. casei at appropriate levels (> 7 log cfu
      ml-1), thereby qualifying as a potential probiotic product. Although both control
      and probiotic beverages exhibited ACE inhibitory activity, as a result of
      proteolysis of whey proteins during fermentation, significant increased ACE
      inhibitory activity was found for the beverage with added probiotic L. casei (P <
      0.05). The probiotic beverage has potency as a functional food candidate to be
      included in a dietary strategy aiming at prevention and control of hypertension.

PMID- 29209905
TI  - Primary central nervous system lymphoma in an immunocompetent patient: an unusual
      case of prolonged response to steroids.

PMID- 29209904
TI  - Association of variants in microRNA with Parkinson's disease in Chinese Han
      population.
AB  - MicroRNAs (miRNAs) are short RNAs regulating gene expression and may participate
      in pathogenesis of various diseases. Recently, rs897984:T > C in miR-4519 and
      rs11651671:A > G in miR-548at-5p have been reported that associate with
      Parkinson's disease (PD). However, to our knowledge, there is no further evidence
      regarding this finding. Herein, we performed a case-control study of 546 PD
      patients and 550 healthy controls to genotype the two single-nucleotide
      polymorphisms (SNPs) to assess their associations with PD. The results showed
      that rs897984 (OR value for C allele = 0.851, 95% CI 0.603-1.201, P = 0.358) in
      miR-4519 and rs11651671 (OR value for G allele = 1.405, 95% CI 0.927-2.131, P =
      0.107) in miR-548at-5p were not associated to PD, which suggest they may not
      contribute to the gene susceptibility of PD at least in Chinese Han population.
      More evidences from larger sample size and other ethnic populations are still
      needed to illustrate the association between miRNAs and PD.

PMID- 29209906
TI  - The fourth annual BRDS on genome editing and silencing for precision medicines.
AB  - Precision medicine is promising for treating human diseases, as it focuses on
      tailoring drugs to a patient's genes, environment, and lifestyle. The need for
      personalized medicines has opened the doors for turning nucleic acids into
      therapeutics. Although gene therapy has the potential to treat and cure genetic
      and acquired diseases, it needs to overcome certain obstacles before creating the
      overall prescription drugs. Recent advancement in the life science has helped to
      understand the effective manipulation and delivery of genome-engineering tools
      better. The use of sequence-specific nucleases allows genetic changes in human
      cells to be easily made with higher efficiency and precision than before.
      Nanotechnology has made rapid advancement in the field of drug delivery, but the
      delivery of nucleic acids presents unique challenges. Also, designing efficient
      and short time-consuming genome-editing tools with negligible off-target effects
      are in high demand for precision medicine. In the fourth annual Biopharmaceutical
      Research and Development Symposium (BRDS) held at the University of Nebraska
      Medical Center (UNMC) on September 7-8, 2017, we covered different facets of
      developing tools for precision medicine for therapeutic and diagnosis of genetic
      disorders.

PMID- 29209907
TI  - Scientific white paper on concentration-QTc modeling.
AB  - The International Council for Harmonisation revised the E14 guideline through the
      questions and answers process to allow concentration-QTc (C-QTc) modeling to be
      used as the primary analysis for assessing the QTc interval prolongation risk of
      new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling
      in early phase 1 studies can be an alternative approach to a thorough QT study
      for some drugs to reliably exclude clinically relevant QTc effects. This white
      paper provides recommendations on how to plan and conduct a definitive QTc
      assessment of a drug using C-QTc modeling in early phase clinical pharmacology
      and thorough QT studies. Topics included are: important study design features in
      a phase 1 study; modeling objectives and approach; exploratory plots; the pre
      specified linear mixed effects model; general principles for model development
      and evaluation; and expectations for modeling analysis plans and reports. The
      recommendations are based on current best modeling practices, scientific
      literature and personal experiences of the authors. These recommendations are
      expected to evolve as their implementation during drug development provides
      additional data and with advances in analytical methodology.

PMID- 29209908
TI  - Purification and Characterization of Exo-Inulinase from Paenibacillus sp. d9
      Strain.
AB  - This study intended to purify and characterise exo-inulinase of diesel-degrading
      Paenibacillus sp. D9. The whole genome sequencing of Paenibacillus sp. D9
      revealed to possess the sacC gene that is encoded as exo-inulinase/levanase. This
      isolate was capable of producing a maximum of 50.9 IU/mL of exo-inulinase
      activity within 3 days at 30  degrees C, 200 rpm and pH of 7.0 on minimal salt
      medium agar supplemented with 1% (w/v) inulin. An exo-inulinase of 58.5 kDa was
      purified using ammonium sulphate precipitation, HiTrap QFF column and MMC column
      chromatographies with a specific activity of 4333 IU/mg, 7.1% recovery and a 4.3
      fold increase in purity. The purified D9 exo-inulinase had temperature and pH
      optimum at 40  degrees C and pH 4.0, respectively, with the Michaelis constant of
      5.5 mM and a maximal velocity of 476.2 IU/mg, respectively. Catalytic constant, k
      cat was calculated to be 42.6 s-1 with a catalytic efficiency (k cat /K m ) of
      7.6 s-1 mM-1. The presence of Ca2+ enhanced the activity of D9 exo-inulinase
      while Hg2+ completely inhibited the activity, other compounds such as Fe3+ and
      Cu2+ had an inhibitory effect. The results of amino acid alignment and the
      complete degradation of inulin into fructose by the purified enzyme confirmed
      that inulinase from Paenibacillus sp. D9 is an exo-form. The phylogenetic tree
      based on the protein sequences indicates that bacterial exo-inulinases possess a
      common ancestry.

PMID- 29209909
TI  - Biochemical and Biophysical Characterisation of Higher Oligomeric Structure of
      Rat Nucleosome Assembly Protein 1.
AB  - Nucleosome assembly protein 1 (NAP1) is a histone chaperone that exchanges
      histone H2A-H2B dimer from chromatin templates. Studies with yeast NAP1 (yNAP1)
      have revealed its existence as multiple oligomeric species in solution. Here, rat
      NAP1 (rNAP1), which is 98% identical to the human NAP1 (hNAP1) was used as a
      model to characterize the oligomeric structures of this protein in higher
      eukaryotes. Gel filtration chromatography and Dynamic light scattering of
      recombinant rNAP1 indicated that the protein exists as a complex mixture of
      multimeric species even at 500 mM ionic strength. The solution-state complexity
      remains unchanged even at higher ionic strengths. Equilibrium unfolding (DeltaG
      14.6 kcal mol- 1) shows that rNAP1, both dimeric and oligomeric, follow the two
      state model of unfolding with no detectable intermediates. Homology modelling
      suggests that rat and yeast NAP1 share an overall similar structure with
      conserved domains. However, dissimilar substitutions like threonine and lysine
      with glycine in the beta-hairpin involved in oligomerization, possibly leads to
      the observed differences in the oligomerization propensity of the two proteins.
      Molecular dynamic simulation (MDS) of the two structures also revealed that rNAP1
      dimer is more stable owing to the extensive hydrogen bonding in comparison to
      yNAP1. Further, in vitro kinase assay showed that the phosphorylation of rNAP1
      favors oligomerization with no effect on its histone binding capacity. Our
      results clearly suggest that there are differences in the in-solution behavior of
      rNAP1 compared to yNAP1 which may have in vivo functional implications for the
      regulation of these complexes during chromatin assembly and rearrangement.

PMID- 29209910
TI  - Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary
      Fibrosis: An Update.
AB  - Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing
      interstitial pneumonia with limited treatment options. In recent years, its
      management has been transformed with the approval of two new antifibrotic drugs:
      nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that
      efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable
      tolerability profile. This article reviews new available evidence on the long
      term efficacy and safety of nintedanib in patients with idiopathic pulmonary
      fibrosis. Data from extension trials indicate that nintedanib continues to slow
      disease progression for up to 3 years and is similarly effective in patients with
      mild and severe impairment of lung function. Treatment with nintedanib reduces
      the risk of acute exacerbations, and a combined analysis of data from clinical
      trials of nintedanib shows a trend towards a reduction in mortality. Nintedanib
      is well tolerated and has been shown to be safe for up to 51 months.
      Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by
      the treatment. Currently available data confirm its safety profile in real-life
      clinical settings, with no new safety concerns identified in patients with
      comorbidities.

PMID- 29209911
TI  - MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal
      Tumor Organoids.
AB  - Patient-derived colorectal tumor organoids (CTOs) closely recapitulate the
      complex morphological, phenotypic, and genetic features observed in in vivo
      tumors. Therefore, evaluation of drug distribution and metabolism in this model
      system can provide valuable information to predict the clinical outcome of a
      therapeutic response in individual patients. In this report, we applied matrix
      assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to
      examine the spatial distribution of the drug irinotecan and its metabolites in
      CTOs from two patients. Irinotecan is a prodrug and is often prescribed as part
      of therapeutic regimes for patients with advanced colorectal cancer. Irinotecan
      shows a time-dependent and concentration-dependent permeability and metabolism in
      the CTOs. More interestingly, the active metabolite SN-38 does not co-localize
      well with the parent drug irinotecan and the inactive metabolite SN-38G. The
      phenotypic effect of irinotecan metabolism was also confirmed by a viability
      study showing significantly reduced proliferation in the drug treated CTOs. MALDI
      MSI can be used to investigate various pharmaceutical compounds in CTOs derived
      from different patients. By analyzing multiple CTOs from a patient, this method
      could be used to predict patient-specific drug responses and help to improve
      personalized dosing regimens. Graphical Abstract ?.

PMID- 29209912
TI  - Restoration of SMN expression in mesenchymal stem cells derived from gene
      targeted patient-specific iPSCs.
AB  - Spinal muscular atrophy (SMA) is primarily a neurodegenerative disease caused by
      the homozygous deletion of the survival motor neuron 1 (SMN1) gene, thereby
      reducing SMN protein expression. Mesenchymal stem cells (MSCs) have been
      implicated in the treatment of SMA. In the present study, we overexpressed
      exogenous SMN1 at the ribosomal DNA (rDNA) locus of induced pluripotent stem
      cells (iPSCs) generated from a SMA patient using an rDNA-targeting vector. The
      gene-targeted patient iPSCs differentiated into MSCs (SMN1-MSCs). A 2.1-fold
      higher expression level of SMN protein was detected in SMN1-MSCs than that
      detected in MSCs derived from patient iPSCs, and the results of the
      immunofluorescence analysis showed no difference in the quantity of SMN nuclear
      structures (gems) between SMN1-MSCs and MSCs derived from normal human iPSCs (h
      MSCs). These findings provide a novel strategy for obtaining gene-targeted MSCs
      for potential clinical applications in autologous cell-based therapy.

PMID- 29209913
TI  - The Influence of Sex Information on Gender Word Processing.
AB  - Three different tasks (word repetition, lexical decision, and gender decision)
      were designed to explore the impact of the sex clues (sex of the speaker, sex of
      the addressee) and the type of gender (semantic, arbitrary) on the processing of
      isolated Spanish gendered words. The findings showed that the grammatical gender
      feature was accessed when no mandatory attentional focus was required. In
      addition, the results indicated that the participants organize information
      according to their own sex role, which provides more salience to the words that
      match in grammatical gender with their own sex role representation, even when the
      gender assignment is arbitrary. Finally, the sex of the speaker biased the
      lexical access and the grammatical gender selection, serving as a semantic prime
      when the two dimensions have a congruent relationship. Furthermore, the masculine
      form serves as the generic gender representing both male and female figures.

PMID- 29209914
TI  - A Mathematical Model Supports a Key Role for Ae4 (Slc4a9) in Salivary Gland
      Secretion.
AB  - We develop a mathematical model of a salivary gland acinar cell with the
      objective of investigating the role of two [Formula: see text] exchangers from
      the solute carrier family 4 (Slc4), Ae2 (Slc4a2) and Ae4 (Slc4a9), in fluid
      secretion. Water transport in this type of cell is predominantly driven by
      [Formula: see text] movement. Here, a basolateral [Formula: see text] adenosine
      triphosphatase pump (NaK-ATPase) and a [Formula: see text]-[Formula: see text]
      [Formula: see text] cotransporter (Nkcc1) are primarily responsible for
      concentrating the intracellular space with [Formula: see text] well above its
      equilibrium potential. Gustatory and olfactory stimuli induce the release of
      [Formula: see text] ions from the internal stores of acinar cells, which triggers
      saliva secretion. [Formula: see text]-dependent [Formula: see text] and [Formula:
      see text] channels promote ion secretion into the luminal space, thus creating an
      osmotic gradient that promotes water movement in the secretory direction. The
      current model for saliva secretion proposes that [Formula: see text] anion
      exchangers (Ae), coupled with a basolateral [Formula: see text] ([Formula: see
      text]) (Nhe1) antiporter, regulate intracellular pH and act as a secondary
      [Formula: see text] uptake mechanism (Nauntofte in Am J Physiol Gastrointest
      Liver Physiol 263(6):G823-G837, 1992; Melvin et al. in Annu Rev Physiol 67:445
      469, 2005. https://doi.org/10.1146/annurev.physiol.67.041703.084745 ). Recent
      studies demonstrated that Ae4 deficient mice exhibit an approximate [Formula: see
      text] decrease in gland salivation (Pena-Munzenmayer et al. in J Biol Chem
      290(17):10677-10688, 2015). Surprisingly, the same study revealed that absence of
      Ae2 does not impair salivation, as previously suggested. These results seem to
      indicate that the Ae4 may be responsible for the majority of the secondary
      [Formula: see text] uptake and thus a key mechanism for saliva secretion. Here,
      by using 'in-silico' Ae2 and Ae4 knockout simulations, we produced mathematical
      support for such controversial findings. Our results suggest that the exchanger's
      cotransport of monovalent cations is likely to be important in establishing the
      osmotic gradient necessary for optimal transepithelial fluid movement.

PMID- 29209915
TI  - Classification of early stage non-small cell lung cancers on computed tomographic
      images into histological types using radiomic features: interobserver delineation
      variability analysis.
AB  - Radiomics, which involves the extraction of large numbers of quantitative
      features from medical images, has attracted attention in cancer research. In
      radiomics analysis, tumor segmentation is a crucial step. In this study, we
      evaluated the potential application of radiomics for predicting the histology of
      early stage non-small cell lung cancer (NSCLC) by analyzing interobserver
      variability in tumor delineation. Forty patient datasets were included in this
      study, 21 involving adenocarcinomas and 19 involving squamous cell carcinomas.
      All patients underwent stereotactic body radiotherapy treatment. In total, 476
      features were extracted from each dataset, representing treatment planning,
      computed tomography images, and gross tumor volume (GTV). The definition of GTV
      can significantly affect the histology prediction. Therefore, in the present
      study, the effect of interobserver tumor delineation variability on radiomic
      features was evaluated by preparing 4 volumes of interest (VOIs) for each
      patient, as follows: the original GTV (which was delineated at treatment
      planning); two GTVs delineated retrospectively by radiation oncologists; and a
      semi-automatic GTV contoured by a medical physicist. Radiomic features extracted
      from each VOI were then analyzed using a naive Bayesian model. Area-under-the
      curve (AUC) analysis showed that interobserver variability in delineation is a
      significant factor in radiomics performance. Nevertheless, with 8 selected
      features, AUC values averaged over the VOIs were high (0.725 +/- 0.070). The
      present study indicated that radiomics has potential for predicting early stage
      NSCLC histology despite variability in delineation. The high prediction accuracy
      implies that noninvasive histology evaluation by radiomics is a promising
      clinical application.

PMID- 29209916
TI  - Carcinogens that induce the A:T > T:A nucleotide substitutions in the genome.
AB  - Recently, Ng et al. reported that the A:T > T:A substitutions, proposed to be a
      signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of
      patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China,
      and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored
      the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4
      aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive
      metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this
      signature in the genome. Since tobacco smoke is a worldwide public health threat
      and vinyl chloride distributes globally and is an air pollutant in Taiwan
      Province, the estimation of the patients' exposure history is the key to
      determine the "culprit" of the A:T > T:A mutations. Apparently, without
      estimation of the patients' exposure history, the conclusion of Ng et al. is
      unpersuasive and misleading.

PMID- 29209917
TI  - Cluster analysis for syndromes of real-world coronary heart disease with angina
      pectoris.
AB  - Syndromes of coronary heart disease with angina pectoris were analyzed to provide
      guidance for clinical practice and to improve accuracy of traditional Chinese
      medicine (TCM) diagnoses and efficacy of TCM treatment. A total of 860 cases with
      coronary heart disease with angina pectoris were selected from TCM Clinical
      Research Information Sharing System for TCM clinics and research. Syndromes were
      automatically extracted with the cluster method and were analyzed to provide
      objective evidence for clinical studies. Final syndrome classifications were
      recognized and confirmed by clinical experts. Popular syndromes included Qi and
      blood deficiency, blood stasis and obstruction collaterals, liver depression and
      spleen deficiency, and Qi stagnation and blood stasis. Syndromes Qi and blood
      deficiency and blood stasis and obstruction collaterals accounted for 28.61% of
      total syndromes, whereas liver depression and spleen deficiency and Qi stagnation
      and blood stasis accounted for 26.44%. The main syndrome elements comprised Qi
      deficiency, blood deficiency, blood stasis, and Qi stagnation.

PMID- 29209918
TI  - Molecular classification and precision therapy of cancer: immune checkpoint
      inhibitors.
AB  - On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment
      for cancer patients with positive microsatellite instability-high (MSI-H) markers
      or mismatch repair deficient (dMMR) markers. This approach is the first approved
      tumor treatment using a common biomarker rather than specified tumor locations in
      the body. FDA previously approved Keytruda for treatment of several types of
      malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer,
      recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and
      urothelial carcinoma, all of which carry positive programmed death-1/programmed
      death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly
      expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR
      and characterized by increased neoantigen load, which elicits intense host immune
      response in tumor microenvironment, including portions of colorectal and gastric
      carcinomas. Currently, biomarker-based patient selection remains a challenge.
      Pathologists play important roles in evaluating histology and biomarker results
      and establishing detection methods. Taking gastric cancer as an example, its
      molecular classification is built on genome abnormalities, but it lacks
      acceptable clinical characteristics. Pathologists are expected to act as "genetic
      interpreters" or "genetic translators" and build a link between molecular
      subtypes with tumor histological features. Subsequently, by using their findings,
      oncologists will carry out targeted therapy based on molecular classification.

PMID- 29209919
TI  - Association between CYP2C19 extensive metabolizer phenotype and childhood anti
      reflux surgery following failed proton pump inhibitor medication treatment.
AB  - : When pediatric gastroesophageal reflux disease (GERD) that is refractory to
      proton pump inhibitor (PPI) medication treatment is identified in clinical
      practice and anti-reflux surgery (ARS) is being considered, genetic factors
      related to PPI metabolism by the CYP2C19 enzyme are currently not part of the
      clinical decision-making process. Our objective was to test the hypothesis that
      the distribution of the extensive metabolizer (EM) phenotypes among children
      undergoing ARS after failing PPI therapy would differ compared to controls
      (children with no history of ARS). We conducted a case-control study between
      children across the Nemours Health System from 2000 to 2014 who received ARS
      after failing PPI therapy and a control group comprised of healthy children. Our
      results demonstrated 2.9% of ARSs vs 20.8% of controls were poor metabolizers
      (PMs), 55.9% of ARSs vs 49.0% of controls were normal metabolizers (NMs), and
      41.2% of ARSs vs 30.2% of controls were EMs; p = 0.035. Next, we performed a
      multiple-regression model to account for race as a potential confounding variable
      and the EM group was significantly associated with ARS compared to controls (OR
      9.78, CI 1.25-76.55, p < 0.03). CONCLUSION: Among children with medically
      refractory GERD despite PPI therapy, carriage of CYP2C19*17 allele corresponding
      to the EM phenotype was associated with ARS. Prospective comparative personalized
      medicine effectiveness studies are needed to determine if CYP2C19 genotype-guided
      dosing improves response to PPI therapy without a corresponding increase in
      adverse effects in children. What is known: * Anti-reflux surgery (ARS) is one of
      the most common surgical procedures performed in children for the indication of
      refractory gastroesophageal reflux disease (GERD). What is new: * Individualizing
      PPI medication dosing based on CYP2C19 diplotype may avoid GERD treatment
      failures and reduce the need for anti-reflux surgery (ARS).

PMID- 29209920
TI  - A Pilot Program Integrating Hepatitis B Virus (HBV) Screening into an Outpatient
      Endoscopy Unit Improves HBV Screening Among an Ethnically Diverse Safety-Net
      Hospital.
AB  - BACKGROUND: Safety-net hospitals are enriched in ethnic minorities and provide
      opportunities for high-impact hepatitis B virus (HBV) screening. AIM: We aim to
      evaluate the impact of a pilot program integrating HBV screening into outpatient
      endoscopy among urban safety-net populations. METHODS: From July 2015 to May
      2017, consecutive adults undergoing outpatient endoscopy were prospectively
      assessed for HBV screening eligibility using US Preventative Services Task Force
      guidelines. Rates of prior HBV screening were assessed, and those eligible but
      not screened were offered HBV testing. Multivariate logistic regression models
      evaluated predictors of test acceptance among eligible patients. RESULTS: Among
      1557 patients (47.1% male, 69.4% foreign born), 65.1% were eligible for HBV
      screening, among which 24.5% received prior screening. In our pilot screening
      program in the endoscopy unit, 91.4% (n = 855) of eligible patients accepted HBV
      testing. However, only 55.3% (n = 415) of those that accepted actually completed
      HBV testing. While there was a trend toward higher rates of test acceptance among
      African-Americans compared to non-Hispanic whites (OR 3.31, 95% CI 0.96-11.38, p
      = 0.06), no other sex-specific or race/ethnicity-specific disparities in HBV test
      acceptance were observed. Among those who completed HBV testing, we identified 10
      new patients with chronic HBV (2.4% prevalence). Only 24.5% of eligible patients
      received prior HBV screening among our cohort. CONCLUSIONS: Our pilot program
      integrating HBV screening into outpatient endoscopy successfully tested an
      additional 415 patients, improving overall HBV screening from 24.5 to 75.6%.
      Integrating HBV testing into non-traditional settings has potential to bridge the
      gap in HBV screening among safety-net systems.

PMID- 29209921
TI  - Fourteen-Year Anti-TNF Therapy in Crohn's Disease Patients: Clinical
      Characteristics and Predictive Factors.
AB  - BACKGROUND: Crohn's disease (CD) is an intractable disease that requires long
      term treatment. Tumor necrosis factor (TNF) inhibitors have strong efficacy and
      are widely used for CD treatment. However, a loss of response is one of the
      issues in long-term TNF therapy. To identify the factors affecting the efficacy
      of long-term CD treatment with TNF inhibitors, we conducted a retrospective study
      of treatment outcomes and clinical factors using clinical data over a 14-year
      period. METHODS: Clinical characteristics and factors for surgery,
      hospitalization, and TNF inhibitor treatment discontinuation were examined in 219
      biologic-naive patients who were treated with TNF inhibitors at our hospital
      before October 2014. RESULTS: Treatment persistence rates with no
      hospitalization, surgery, or dose escalation were 60.7, 25.9, and 17.3% for 1, 5,
      and 10 years, respectively; these rates did not differ between infliximab (IFX)
      and adalimumab. In patients receiving IFX dose escalation, 1- and 5-year
      persistence rates were approximately 90.4 and 65.1%, respectively. Previous
      surgery (OR = 1.45, P = 0.043) was identified as a risk factor for surgery, male
      sex (OR = 0.70, P = 0.044) and previous surgery (OR = 1.51, P = 0.03) were risk
      factors for hospitalization, and perianal fistula (OR = 1.39, P = 0.049) was the
      risk factor for TNF inhibitor treatment discontinuation. CONCLUSIONS: The
      durability of anti-TNF therapy in CD patients remains a problem, and treatment
      optimization that includes dose escalation should be carefully examined depending
      on patient characteristics and the timing of optimization.

PMID- 29209922
TI  - Altered brain morphometry in 7-year old HIV-infected children on early ART.
AB  - Even with the increased roll out of combination antiretroviral therapy (cART),
      paediatric HIV infection is associated with neurodevelopmental delays and
      neurocognitive deficits that may be accompanied by alterations in brain
      structure. Few neuroimaging studies have been done in children initiating ART
      before 2 years of age, and even fewer in children within the critical stage of
      brain development between 5 and 11 years. We hypothesized that early ART would
      limit HIV-related brain morphometric deficits at age 7. Study participants were 7
      year old HIV-infected (HIV+) children from the Children with HIV Early
      Antiretroviral Therapy (CHER) trial whose viral loads were supressed at a young
      age, and age-matched uninfected controls. We used structural magnetic resonance
      imaging (MRI) and FreeSurfer ( http://www.freesurfer.net/ ) software to
      investigate effects of HIV and age at ART initiation on cortical thickness,
      gyrification and regional brain volumes. HIV+ children showed reduced
      gyrification compared to controls in bilateral medial parietal regions, as well
      as reduced volumes of the right putamen, left hippocampus, and global white and
      gray matter and thicker cortex in small lateral occipital region. Earlier ART
      initiation was associated with lower gyrification and thicker cortex in medial
      frontal regions. Although early ART appears to preserve cortical thickness and
      volumes of certain brain structures, HIV infection is nevertheless associated
      with reduced gyrification in the parietal cortex, and lower putamen and
      hippocampus volumes. Our results indicate that in early childhood gyrification is
      more sensitive than cortical thickness to timing of ART initiation. Future work
      will clarify the implications of these morphometric effects for
      neuropsychological function.

PMID- 29209923
TI  - Plasma microparticles in Alzheimer's disease: The role of vascular dysfunction.
AB  - Cerebrovascular lesions, a potent stimulus for endothelial cell activation,
      trigger cognitive and degenerative changes and contribute to pathology of
      Alzheimer's disease (AD). Circulating microparticles (MPs) are actively involved
      in the pathogenesis of AD and cerebrovascular diseases, which share common
      vascular risk factors. We examined the plasma changes of endothelial MPs (EMPs)
      and platelet MPs (PMPs) in AD patients with vascular risk factors. The plasma
      Annexin V+ CD 41a- CD144+ EMPs and Annexin V+ CD41a+ CD144- PMPs of 37 patients
      with AD, with or without vascular risk factors (hypertension, diabetes,
      dyslipidemia, stroke, coronary artery disease, and smoking), and 10 age-matched
      controls were quantified by flow cytometry. Pearson correlation analysis used to
      evaluate the linear relationship between variables. Significantly higher plasma
      levels of EMPs were observed in AD patients with vascular risk factors as
      compared to the patients without vascular risk factors [Mean Difference (MD):
      2587.80, 95% confidence interval (CI) 770.30-4404.80], and control subjects (MD:
      4990.60, 95% CI, 3054.40-6926.79). Significant correlations were found between
      circulating EMPs, total MPs, and PMPs. There were no significant correlations
      between plasma levels of EMPs/ PMPs, and cognitive decline indices. Circulating
      EMP levels are influenced by AD disease status, and plasma levels of MPs and PMPs
      are associated with vascular risk factors in patients with AD. EMP phenotyping,
      as cellular biomarkers of vascular injury/dysfunction, and their effects on
      cerebral perfusion, and cognitive decline should be further investigated.
      Graphical abstract Vascular endothelial cell activation results in release of
      endothelial-derived microparticles (EMPs), which contributing to vascular
      dysfunction and cognitive decline.

PMID- 29209925
TI  - Preventing hypotension-induced nausea and vomiting during spinal anesthesia for
      Cesarean delivery in obese parturients: a small solution for a big problem?

PMID- 29209926
TI  - A randomized trial of phenylephrine infusion versus bolus dosing for nausea and
      vomiting during Cesarean delivery in obese women.
AB  - PURPOSE: Hypotension is common after spinal anesthesia for Cesarean delivery. It
      is associated with nausea, vomiting, and fetal acidosis. Previous research on
      phenylephrine excluded obese subjects. We compared the incidence of
      intraoperative nausea and vomiting (IONV) in obese patients who received a
      prophylactic phenylephrine infusion vs those who received bolus dosing for the
      treatment of spinal-induced hypotension. METHODS: In this multicentre, double
      blinded randomized controlled trial, 160 obese women undergoing elective Cesarean
      delivery under spinal anesthesia were randomized to receive a prophylactic
      phenylephrine infusion initiated at 50 MUg.min-1 (and titrated according to a
      predefined algorithm) or 100 MUg phenylephrine boluses to treat hypotension.
      Maternal systolic blood pressure was maintained within 20% of baseline. The
      primary study outcome was the incidence of IONV. RESULTS: Intraoperative nausea
      and vomiting were significantly reduced in the infusion group compared to the
      bolus group (46% vs 75%, respectively; relative risk [RR], 0.61; 95% confidence
      interval [CI], 0.47 to 0.80; P < 0.001). This was associated with significantly
      reduced need for intraoperative rescue antiemetics (26% vs 42%, respectively; RR,
      0.62; 95% CI, 0.40 to 0.97; P = 0.04), but no difference in the incidence of
      vomiting. Postoperative vomiting at two hours was reduced in the infusion group
      (11% vs 25%; RR, 0.44; 95% CI, 0.21 to 0.90; P = 0.02);however, there were no
      differences in the incidence or severity of postoperative nausea, need for rescue
      antiemetics at two hours and 24 hr, or the incidence of postoperative vomiting at
      24 hr. CONCLUSION: In obese women undergoing Cesarean delivery with spinal
      anesthesia, prophylactic phenylephrine infusion was associated with less
      intraoperative nausea, less need for rescue antiemetics, and reduced early
      postoperative vomiting. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01481740).
      Registered 22 July 2011.

PMID- 29209924
TI  - Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of
      four treatment regimens.
AB  - Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all
      adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is
      effective but associated with considerable toxicity. In this observational study,
      we compared real-world efficacy, toxicity, and costs of four frequently employed
      treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the
      Berlin-Frankfurt-Munster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We
      collected data from 147 adult patients treated in eight referral centers.
      Following central pathology assessment, 105 of these cases were accepted as
      Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients,
      BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39
      years, range 14-74; mean duration of follow-up 47 months). There was no
      significant difference between age, sex ratio, disease stage, or percentage HIV
      positive patients between the treatment groups. Five-year progression-free
      survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were
      comparable for all treatment groups. Treatment-related toxicity was also
      comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC
      group (p = 0.004). Costs were determined by the number of rituximab gifts and the
      number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile
      with regards to costs, treatment duration, and percentage of patients completing
      planned treatment. We conclude that the four treatment protocols for Burkitt
      lymphoma yield nearly identical results with regards to efficacy and safety but
      differ in treatment duration and costs. These differences may help guide future
      choice of treatment.

PMID- 29209927
TI  - Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a
      case series.
AB  - PURPOSE: Vasoplegia is a clinical syndrome marked by severe arteriolar
      vasodilatation, hypotension, and low systemic vascular resistance refractory to
      multiple vasopressor treatment. We report our experience with hydroxocobalamin
      (B12) infusion as a potential rescue adjunct for refractory vasoplegia during
      cardiopulmonary bypass (CPB). METHODS: We performed a retrospective chart review
      of 33 patients undergoing cardiac surgery between 1 January 2013 and 31 December
      2015, who were given intravenous B12 for refractory hypotension during, or
      immediately following, CPB. We assessed mean arterial pressure (MAP) responses
      using semi-parametric group-based models (trajectory analysis). Vasopressor use
      was evaluated by norepinephrine-equivalent rates calculated five minutes prior,
      and up to 60 min following, B12 administration. RESULTS: Patients were mostly
      male (82%), had a mean (SD) age of 53 (13) yr, and median (IQR) EuroSCORE
      mortality index of 9 [4-40]. Four patterns of MAP responses to B12 were
      identified. In Group 1 ("poor responders") nine of 33 patients (27%) had the
      highest median [IQR] mortality risk (EuroSCORE 40 [4-52]), lowest mean pre-B12
      MAP (50 mmHg), and minimal hemodynamic response in spite of continued vasopressor
      support. In contrast, Group 2 "responders" (8/33, 24%) showed a brisk MAP
      response (> 15 mmHg) to B12, sustained for > 60 min post-infusion, with 50%
      vasopressor reduction. Groups 3 and 4 had the lowest median mortality risk
      (EuroSCORE 8) and highest pre-B12 MAP (72 mmHg). Although Group 3 patients
      ("sustainers"; 9/33, 27%) showed a sustained MAP improvement, those in Group 4
      ("rebounders"; 7/33, 21%) were characterized by hypertensive overshoot followed
      by a decrease in MAP. CONCLUSION: These data indicate considerable heterogeneity
      in patient response to B12, potentially dependent on both patient preoperative
      condition and non-standardized time of administration. B12 may provide a useful
      alternative therapy for refractory hypotension and vasoplegia, but controlled
      clinical trials to assess efficacy are needed.

PMID- 29209928
TI  - Subclavian and axillary vessel anatomy: a prospective observational ultrasound
      study.
AB  - PURPOSE: The primary objective of this study was to define the ultrasound-derived
      anatomy of the axillary/subclavian vessels. As a secondary objective, we
      evaluated the relationship between the vascular anatomy and demographic,
      anthropometric, and hemodynamic data of patients. METHODS: This observational
      anatomical study used bedside ultrasound with 150 cardiac surgical patients in
      the operating room. Bilateral axillary and subclavian anatomy was determined
      using a high-frequency ultrasound probe with fixed reference points. Images were
      recorded and analyzed, and correlation with demographic, anthropometric, and
      hemodynamic data was performed. RESULTS: The images were adequate to evaluate
      potential anatomical variations in 97.4% of patients with a body mass index as
      high as 46.4 kg.m-2. The mean (standard deviation) diameter of the axillary vein
      was 1.2 (0.3) cm on the right side and 1.1 (0.2) cm on the left side. The
      dimensions of the axillary vein were larger on the right side in 69% of patients.
      The vein was located directly over the artery in the mid-clavicular view in 67%
      of the patients and in lateral-clavicular view in only 7% of the patients. As we
      moved the probe laterally, the vein was lateralized in relation to the artery in
      89% of patients. There was no significant correlation between the hemodynamic
      data and vessel size, although direct correlation was found between body mass
      index and the depth of the vessel (P < 0.001). The axillary vein area was smaller
      in females than in males (P < 0.002), and in 4% of patients, the axillary vein
      was in an aberrant position. CONCLUSIONS: In patients undergoing cardiac surgery,
      axillary vessel anatomy varied considerably, and the patients' hemodynamics could
      not predict the size of the axillary vessels. Only the patients' weight
      correlated moderately with the depth of the vein.

PMID- 29209929
TI  - Statistical reporting and table construction guidelines for publication in the
      Canadian Journal of Anesthesia.

PMID- 29209930
TI  - A Psychometric Validation of the Employers' Stigmatizing Attitudes Toward Cancer
      Survivors Scale.
AB  - Purpose The aim of this study was to evaluate the measurement structure of the
      Employers' Stigmatizing Attitudes Toward Cancer Survivors Scale (ESATPD-Cancer
      Scale). Methods A quantitative descriptive design using exploratory factor
      analysis (EFA) and confirmatory factor analysis (CFA). One hundred and seventy
      seven Taiwanese human resources (HR) professionals participated in this study.
      Results EFA revealed a one-factor measurement structure accounting for 50% of the
      total variance. We conducted a CFA to confirm the one-factor structure; after two
      pairs of error terms were correlated, the re-specified model was found to fit the
      data adequately: chi2/df = 1.69, GFI = 0.97, CFI = 0.98, and RMSEA = 0.06.
      Internal consistency reliability coefficient (Cronbach's alpha) for the ESATPD
      Cancer Scale was computed to be 0.80. In addition, stigmatizing attitudes were
      found to be negatively associated with HR professionals' willingness to hire
      cancer survivors. Conclusions The results of this study support a one-factor
      measurement structure for the ESATPD-Cancer Scale in a sample of HR professionals
      in Taiwan. Findings also support a relationship between ESATPD-Cancer Scale
      scores and HR professionals' willingness to hire cancer survivors, demonstrating
      support for the construct validity of the scale.

PMID- 29209931
TI  - Co-morbid Non-communicable Diseases and Associated Health Service Use in African
      and Caribbean Immigrants with HIV.
AB  - We sought to characterize non-communicable disease (NCD)-related and overall
      health service use among African and Caribbean immigrants living with HIV between
      April 1, 2010 and March 31, 2013. We conducted two population-based analyses
      using Ontario's linked administrative health databases. We studied 1525 persons
      with HIV originally from Africa and the Caribbean. Compared with non-immigrants
      with HIV (n = 11,931), African and Caribbean immigrants had lower rates of
      hospital admissions, emergency department visits and non-HIV specific ambulatory
      care visits, and higher rates of health service use for hypertension and
      diabetes. Compared with HIV-negative individuals from these regions (n =
      228,925), African and Caribbean immigrants with HIV had higher rates of health
      service use for chronic obstructive pulmonary disease [rate ratio (RR) 1.78; 95%
      confidence interval (CI) 1.36-2.34] and malignancy (RR 1.20; 95% CI 1.19-1.43),
      and greater frequency of hospitalizations for mental health illness (RR 3.33; 95%
      CI 2.44-4.56), diabetes (RR 1.37; 95% CI 1.09-1.71) and hypertension (RR 1.85;
      95% CI 1.46-2.34). African and Caribbean immigrants with HIV have higher rates of
      health service use for certain NCDs than non-immigrants with HIV. The evaluation
      of health services for African and Caribbean immigrants with HIV should include
      indicators of NCD care that disproportionately affect this population.

PMID- 29209932
TI  - Intraspecific Variation in Nutritional Composition Affects the Leaf Age
      Preferences of a Mammalian Herbivore.
AB  - Ecologists have long been interested in how the nutritional composition of leaves
      changes as they age, and whether this affects herbivore feeding preferences. As a
      consequence, the literature abounds with reports that younger leaves contain
      higher concentrations of nitrogen and plant secondary metabolites (PSMs) than do
      older leaves. Most of these studies, however, base their conclusions on average
      values that often mean little to herbivores. We examined this issue in the well
      studied marsupial-eucalypt system, using Eucalyptus melliodora and captive common
      brushtail possums (Trichosurus vulpecula) offered branches from individual trees
      containing both young and mature leaves. Like many plants, the concentrations of
      N and PSMs differed among individual E. melliodora. Although young leaves were,
      on average, "better defended" by the PSM sideroxylonal than were mature leaves,
      some trees produced leaves that were relatively undefended at both ages. In
      response, possums chose different proportions of young and mature leaves
      depending on the chemistry of the individual tree. Possums did not always prefer
      leaves with lower concentrations of sideroxylonal (mature leaves) or those with
      higher concentrations of available N (young leaves). Instead, the sideroxylonal
      concentration of young leaves dictated their choice: possums preferred young
      leaves with low sideroxylonal concentrations, but not with high concentrations.
      By skewing their feeding toward trees producing young leaves with low
      concentrations of PSMs, possums may influence plant fitness. Researchers will
      detect these potentially important interactions only if they are aware that
      measuring variation among plants discloses more information than do average
      relationships.

PMID- 29209933
TI  - Evaluating the Role of Drone-Produced Chemical Signals in Mediating Social
      Interactions in Honey Bees (Apis mellifera).
AB  - Pheromones play a critical role in shaping societies of social insects, including
      honey bees, Apis mellifera. While diverse functions have been ascribed to queen-
      and worker-produced compounds, few studies have explored the identity and
      function of male-produced (drone) compounds. However, several lines of evidence
      suggest that drones engage in a variety of social interactions inside and outside
      of the colony. Here we elucidate the chemical composition of extracts of the
      drone mandibular gland, and test the hypothesis that compounds produced in these
      glands, or a synthetic blend consisting of the six main compounds, mediate drone
      social interactions in and out of the colony. Drone mandibular glands primarily
      produce a blend of saturated, unsaturated and methyl branched fatty acids ranging
      in chain length from nonanoic to docosanoic acids, and both gland extracts and
      synthetic blends of these chemicals serve to attract drones outside of the hive,
      but do not attract workers inside the hive. These studies shed light on the role
      drones and drone-produced chemicals have on mediating social interactions with
      other drones and highlight their potential importance in communicating with other
      castes.

PMID- 29209935
TI  - Correction to: Postoperative atrial fibrillation is less frequent in pulmonary
      segmentectomy compared with lobectomy.
AB  - In the original publication of this article, the Table 1 was published
      incorrectly with missing data.

PMID- 29209934
TI  - Variability in Sexual Pheromones Questions their Role in Bumblebee Pre-Mating
      Recognition System.
AB  - Sex-specific chemical secretions have been widely used as diagnostic characters
      in chemotaxonomy. The taxonomically confused group of bumblebees has reaped the
      benefit of this approach through the analyses of cephalic labial gland secretions
      (CLGS). Most of currently available CLGS descriptions concern species from the
      West-Palearctic region but few from the New World. Here, the CLGS of four East
      Palearctic species Bombus deuteronymus, B. filchnerae, B. humilis, and B. exil
      (subgenus Thoracobombus) are analysed. Our results show high levels of
      variability in the major compounds in B. exil. In contrast, we describe a low
      differentiation in CLGS compounds between B. filchnerae and its phylogenetically
      closely related taxon B. muscorum. Moreover, the chemical profiles of B.
      filchnerae and B. muscorum are characterized by low concentrations of the C16
      component, which is found in higher concentrations in the other Thoracobombus
      species. This raises the possibility that courtship behavior as well as
      environmental constraints could affect the role of the bumblebee males' CLGS.

PMID- 29209936
TI  - Plasma lipidomics as a diagnostic tool for peroxisomal disorders.
AB  - Peroxisomes are ubiquitous cell organelles that play an important role in lipid
      metabolism. Accordingly, peroxisomal disorders, including the peroxisome
      biogenesis disorders and peroxisomal single-enzyme deficiencies, are associated
      with aberrant lipid metabolism. Lipidomics is an emerging tool for diagnosis,
      disease-monitoring, identifying lipid biomarkers, and studying the underlying
      pathophysiology in disorders of lipid metabolism. In this study, we demonstrate
      the potential of lipidomics for the diagnosis of peroxisomal disorders using
      plasma samples from patients with different types of peroxisomal disorders. We
      show that the changes in the plasma profiles of phospholipids, di- and
      triglycerides, and cholesterol esters correspond with the characteristic
      metabolite abnormalities that are currently used in the metabolic screening for
      peroxisomal disorders. The lipidomics approach, however, gives a much more
      detailed overview of the metabolic changes that occur in the lipidome.
      Furthermore, we identified novel unique lipid species for specific peroxisomal
      diseases that are candidate biomarkers. The results presented in this paper show
      the power of lipidomics approaches to enable the specific diagnosis of different
      peroxisomal disorders.

PMID- 29209938
TI  - Sauna bathing and systemic inflammation.
AB  - We aimed to investigate whether frequency of sauna bathing is associated with the
      levels of serum C-reactive protein. C-reactive protein is a leading blood marker
      of systemic inflammation. The study consisted of 2084 men (42-60 years) without
      acute or chronic inflammation. A total of 533 (25.6%), 1368 (65.6%), and 183
      (8.8%) participants reported having a sauna bath once a week, 2-3 times, and 4-7
      times per week; mean serum C-reactive protein levels were 2.41 (standard
      deviation 2.91), 2.00 (2.41), 1.65 (1.63) mmol/L, respectively. In a
      multivariable analysis adjusted for baseline age, body mass index, systolic blood
      pressure, smoking, type 2 diabetes, previous myocardial infarction, and serum low
      density lipoprotein cholesterol, alcohol consumption and physical activity, there
      was a significant inverse association between the frequency of sauna bathing and
      the level of C-reactive protein. Further studies are warranted to investigate the
      relationship between sauna bathing and systemic inflammation.

PMID- 29209937
TI  - Sugar-based collagen membrane cross-linking increases barrier capacity of
      membranes.
AB  - OBJECTIVES: This study examines the permeability and barrier capacity of a sugar
      cross-linked resorbable collagen membrane ex vivo and in vivo. MATERIALS AND
      METHODS: In an ex vivo study, injectable platelet-rich fibrin (i-PRF), a
      peripheral blood-derived human leukocyte-and-platelet-rich plasma was used to
      analyze membrane permeability. in vivo subcutaneous implantation in Wistar rats
      (n = 4 per time point and group) was used to investigate the barrier capacity of
      the membrane. The induced in vivo cellular reaction was evaluated at 3, 15, and
      30 days and compared to sham OP (control) without biomaterial using histological,
      immunohistochemical, and histomorphometric methods. RESULTS: Ex vivo, the
      membrane was impenetrable to leukocytes, platelets, and fibrin from peripheral
      human blood concentrate (PRF). In vivo, the membrane maintained its structure and
      remained impervious to cells, connective tissue, and vessels over 30 days. CD-68
      positive cell (macrophage) numbers significantly decreased from 3 to 15 days,
      while from day 15 onwards, the number of multinucleated giant cells (MNGCs)
      increased significantly. Correspondingly, a rise in implantation bed
      vascularization from 15 to 30 days was observed. However, no signs of degradation
      or material breakdown were observed at any time point. CONCLUSION: Ex vivo and in
      vivo results showed material impermeability to cellular infiltration of human and
      murine cells, which highlights the membrane capacity to serve as a barrier over
      30 days. However, whether the induced MNGCs will lead to material degradation or
      encapsulation over the long term requires further investigation. CLINICAL
      RELEVANCE: The data presented are of great clinical interest, as they contribute
      to the ongoing discussion concerning to what extent an implanted material should
      be integrated versus serving only as a barrier membrane.

PMID- 29209939
TI  - Disaggregating the mortality reductions due to cancer screening: model-based
      estimates from population-based data.
AB  - The mortality impact in cancer screening trials and population programs is
      usually expressed as a single hazard ratio or percentage reduction. This measure
      ignores the number/spacing of rounds of screening, and the location in follow-up
      time of the averted deaths vis-a-vis the first and last screens. If screening
      works as intended, hazard ratios are a strong function of the two Lexis time
      dimensions. We show how the number and timing of the rounds of screening can be
      included in a model that specifies what each round of screening accomplishes. We
      show how this model can be used to disaggregate the observed reductions (i.e.,
      make them time-and screening-history specific), and to project the impact of
      other regimens. We use data on breast cancer screening to illustrate this model,
      which we had already described in technical terms in a statistical journal. Using
      the numbers of invitations different cohorts received, we fitted the model to the
      age- and follow-up-year-specific numbers of breast cancer deaths in Funen,
      Denmark. From November 1993 onwards, women aged 50-69 in Funen were invited to
      mammography screening every two years, while those in comparison regions were
      not. Under the proportional hazards model, the overall fitted hazard ratio was
      0.82 (average reduction 18%). Using a (non-proportional-hazards) model that
      included the timing information, the fitted reductions ranged from 0 to 30%,
      being largest in those Lexis cells that had received the greatest number of
      invitations and where sufficient time had elapsed for the impacts to manifest.
      The reductions produced by cancer screening have been underestimated by
      inattention to their timing. By including the determinants of the hazard ratios
      in a regression-type model, the proposed approach provides a way to disaggregate
      the mortality reductions and project the reductions produced by other
      regimes/durations.

PMID- 29209940
TI  - Epidemiological changes in rubella IgG antibody levels detected in antenatal
      women from a retrospective rubella seroprevalence study.
AB  - BACKGROUND: Rubella is caused by the rubella virus, a single-stranded RNA virus
      of the Togaviridae family. The most severe complications of rubella in adult
      women occur during pregnancy when infection can lead to miscarriage, stillbirth
      or congenital rubella syndrome. Antenatal rubella susceptibility screening is no
      longer performed in England, Scotland or Wales but continues in Northern Ireland.
      AIM: The aims of this seroprevalence study were to (1) determine amongst women
      presenting for antenatal care the percentage of women who are rubella
      susceptible, rubella immune and those with equivocal rubella antibody levels by
      year of birth and (2) to consider how rubella vaccination resources can best be
      utilised. METHODS: A retrospective study was performed analysing all antenatal
      rubella IgG antibody tests performed between January 2015 and June 2017 inclusive
      (n = 19,000; excluding duplicate tests). All antenatal women were included
      regardless of the country of origin and age. RESULTS: From our analysis, 88.7% (n
      = 16,868) women had plasma concentrations of anti-rubella IgG > 10 IU/ml. 7.3% of
      women (n = 1403) had rubella IgG levels between 5 and 9.99 IU/ml, and 2.8% (n =
      729) had IgG levels < 5 IU/ml. A decline in rubella immunity in younger women was
      evident. CONCLUSIONS: This study has identified an increase in women who are
      rubella susceptible and women with equivocal rubella antibody levels.
      International evidence suggests that rubella serology is unreliable and antenatal
      screening does not confer any benefit to women during their current pregnancy.
      Consideration should be given to re-direct resources currently utilised for
      antenatal screening to facilitate the vaccination of pre-pregnancy and postpartum
      women and also to opportunistically offer vaccination to all women of
      childbearing age.

PMID- 29209941
TI  - T2238C Atrial Natriuretic Peptide Gene Variant and the Response to Antiplatelet
      Therapy in Stable Ischemic Heart Disease Patients.
AB  - The T2238C variant of the ANP gene is associated with higher risk of major
      cardiovascular events. The purpose of this study is to investigate if this
      polymorphism influences the response to antiplatelet agents and it is responsible
      of increased platelet reactivity, thus contributing to the adverse outcome. In
      patients undergoing elective percutaneous coronary intervention (PCI), loaded
      with antiplatelets, blood samples were withdrawn for genotyping, platelet
      reactivity assessment and for troponin T measurement to investigate the
      association between the polymorphism with residual platelet reactivity and with
      the incidence of PPMI. No significant differences in platelet reactivity nor in
      PPMI incidence were observed between groups. Nevertheless, higher ARU, PRU, and %
      PI were detected in diabetic patients, with PRU significantly higher in carriers
      versus non-carriers. We observed increased residual platelet reactivity
      exclusively in diabetic carriers of the T2238C variant undergoing elective PCI,
      suggesting the need of a more effective platelet inhibition in this category of
      patients.

PMID- 29209942
TI  - The contribution of stimulus frequency and recency to set-size effects.
AB  - Hick's law describes the increase in choice reaction time (RT) with the number of
      stimulus-response (S-R) mappings. However, in choice RT experiments, set-size is
      typically confounded with stimulus recency and frequency: With a smaller set
      size, each stimulus occurs on average more frequently and more recently than with
      a larger set-size. To determine to what extent stimulus recency and frequency
      contribute to the set-size effect, stimulus set-size was manipulated
      independently of stimulus recency and frequency, by keeping recency and frequency
      constant for a subset of the stimuli. Although this substantially reduced the set
      size effect (by approximately two-thirds for these stimuli), it did not eliminate
      it. Thus, the time required to retrieve an S-R mapping from memory is (at least
      in part) determined by the number of alternatives. In contrast, a recent task
      switching study (Van 't Wout et al. in Journal of Experimental Psychology:
      Learning, Memory & Cognition., 41, 363-376, 2015) using the same manipulation
      found that the time required to retrieve a task-set from memory is not influenced
      by the number of alternatives per se. Hence, this experiment further supports a
      distinction between two levels of representation in task-set control: The level
      of task-sets, and the level of S-R mappings.

PMID- 29209943
TI  - Mapping toxic mineral contamination: the southern oyster drill, S. haemastoma
      (L., 1767), as evaluable sentinel species.
AB  - The nickel, chromium, arsenic, cadmium, and lead content have been evaluated, by
      ICP-MS, in digestive gland of the amphiatlantic gastropod Stramonita haemastoma,
      sampled along the highly anthropized Gulf of Milazzo (Central Mediterranean).
      Concentrations notably higher than those reported in literature for other
      Mediterranean Muricidae have been recorded. The results also indicated a
      different impact in different sites, according to distribution and typology of
      human activities, whilst recorded seasonal variations might relate with rapid
      metabolic response. Such preliminary results suggest S. haemastoma may be
      considered a promising sentinel species for inorganic contamination in marine
      environment, especially in terms of short-medium-term exposure.

PMID- 29209944
TI  - The Second Asian Radiology Summit : Residency training program and board
      examination of radiology and imaging in Asia.

PMID- 29209945
TI  - Psoriasis in Skin of Color: Insights into the Epidemiology, Clinical
      Presentation, Genetics, Quality-of-Life Impact, and Treatment of Psoriasis in Non
      White Racial/Ethnic Groups.
AB  - Psoriasis is a chronic inflammatory skin condition affecting diverse
      racial/ethnic groups throughout the world. Large population-based studies suggest
      that psoriasis occurs most often in individuals of European ancestry, followed by
      black and Hispanic individuals, although the true prevalence of psoriasis in non
      white individuals is likely underestimated. Despite similarities in psoriasis
      between ethnic groups, there are notable differences in the presentation, quality
      of-life impact, and treatment of psoriasis with important implications for the
      management of non-white individuals. Overall, heterogeneity in psoriasis
      susceptibility alleles, in combination with cultural and socioeconomic factors,
      may explain these differences. In this article, we review the epidemiology,
      clinical presentation, genetic polymorphisms, quality-of-life impact, and
      treatment nuances of psoriasis in patients with skin of color.

PMID- 29209946
TI  - Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients
      with Active Moderate-to-Severe Rheumatoid Arthritis.
AB  - INTRODUCTION: Sarilumab is a human monoclonal antibody that blocks the
      interleukin-6 receptor alpha (IL-6Ralpha). The phase 3 SARIL-RA-EASY study (EASY)
      assessed the robustness of an autoinjector (pen) for administering sarilumab when
      used by adults with active moderate-to-severe rheumatoid arthritis (RA) who are
      candidates for anti-IL-6R therapy in an unsupervised real-world setting. METHODS:
      EASY was a 12-week, multicenter, randomized, open-label, parallel-group usability
      study of the sarilumab pen and prefilled syringe. Patients were randomized
      1:1:1:1 to sarilumab 150 or 200 mg every 2 weeks (q2w) administered via pen or
      syringe, plus background disease-modifying antirheumatic drugs. Patients reported
      their ability to remove the pen cap and initiate and complete injections;
      negative responses were defined as product technical complaints (PTCs). The
      primary endpoint was the number of validated product technical failures (PTFs;
      PTC with a validated technical cause). This study was not powered to demonstrate
      bioequivalence or differences in efficacy among groups. RESULTS: A total of 217
      patients were randomized. There were 600 successful injections with the sarilumab
      pen in 108 patients and no pen-associated PTFs. One PTC was observed (the pen was
      mistakenly activated before injection). At week 12, 88% of patients indicated the
      pen was "easy" to use, and 98% reported they were "satisfied" with the pen.
      Proportions of patients achieving an American College of Rheumatology 20/50/70
      response and a 28-joint disease activity score by C-reactive protein < 2.6 were
      similar at each dose between the pen and syringe groups, as were the
      pharmacokinetics. There were no clinically meaningful differences in adverse
      events (AEs), serious AEs, and AEs leading to discontinuation in the pen and
      syringe groups. The most common treatment-emergent AEs were infections and
      neutropenia. CONCLUSION: This study demonstrated the ease of use and robustness
      of the sarilumab pen when used by patients with RA in an unsupervised setting.
      Pharmacokinetics, safety, and efficacy were generally similar for the pen and
      syringe groups (NCT02057250). FUNDING: Sanofi Genzyme and Regeneron
      Pharmaceuticals, Inc. TRIAL REGISTRATION: Clinicaltrials.gov identifier,
      NCT02057250.

PMID- 29209947
TI  - Copy number variation arising from gene conversion on the human Y chromosome.
AB  - We describe the variation in copy number of a ~ 10 kb region overlapping the long
      intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat
      on the short arm of the human Y chromosome, leading to individuals with 0-3
      copies of this region in the general population. Variation of this CNV is common,
      with 266 individuals having 0 copies, 943 (including the reference sequence)
      having 1, 23 having 2 copies, and two having 3 copies, and was validated by
      breakpoint PCR, fibre-FISH, and 10* Genomics Chromium linked-read sequencing in
      subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in
      copy number to the phylogeny of these Y chromosomes previously established by the
      Project identified at least 20 mutational events, and investigation of flanking
      paralogous sequence variants showed that the mutations involved flanking
      sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene
      conversion or double crossover between misaligned sister chromatids could
      formally explain the 0-2 copy events, gene conversion is the more likely
      mechanism, and these events include the longest non-allelic gene conversion
      reported thus far. Chromosomes with three copies of this CNV have arisen just
      once in our data set via another mechanism: duplication of 420 kb that places the
      third copy 230 kb proximal to the existing proximal copy. Our results establish
      gene conversion as a previously under-appreciated mechanism of generating copy
      number changes in humans and reveal the exceptionally large size of the
      conversion events that can occur.

PMID- 29209948
TI  - Iron metabolism and related diseases: an overview.

PMID- 29209949
TI  - 18F-FDG PET/CT for the quantification of inflammation in large carotid artery
      plaques.
AB  - BACKGROUND: There is currently no consensus on the methodology for quantification
      of 18F-FDG uptake in inflammation in atherosclerosis. In this study, we explore
      different methods for quantification of 18F-FDG uptake in carotid atherosclerotic
      plaques and correlate the uptake values to histological assessments of
      inflammation. METHODS AND RESULTS: Forty-four patients with atherosclerotic
      stenosis >=70% of the internal carotid artery underwent 18F-FDG PET/CT. Maximum
      standardized uptake values (SUVmax) from all plaque-containing slices were
      collected. SUVmax for the single highest and the mean of multiple slices with and
      without blood background correction (by subtraction (cSUV) or by division (target
      to-background ratio (TBR)) were calculated. Following endarterectomy 30 plaques
      were assessed histologically. The length of the plaques at CT was 6-32 mm. The
      18F-FDG uptake in the plaques was 1.15-2.66 for uncorrected SUVs, 1.16-3.19 for
      TBRs, and 0.20-1.79 for cSUVs. There were significant correlations between the
      different uptake values (r = 0.57-0.99, P < 0.001). Methods with and without
      blood background correction showed similar, moderate correlations to the amount
      of inflammation assessed at histology (r = 0.44-0.59, P < 0.02). CONCLUSIONS: In
      large stenotic carotid plaques, 18F-FDG uptake reflects the inflammatory status
      as assessed at histology. Increasing number of PET slices or background
      correction did not change the correlation.

PMID- 29209950
TI  - SPECT myocardial ischemia in the absence of obstructive CAD: Contribution of the
      invasive assessment of microvascular dysfunction.
AB  - Coronary microvascular dysfunction has recently emerged as a major independent
      prognostic factor and can be invasively assessed by coronary flow reserve (CFR)
      and the index of microvascular resistance (IMR). The incremental prognostic value
      of myocardial ischemia from SPECT myocardial perfusion imaging (MPI) over
      clinical characteristics, cardiac risk factors, and stress test data for the
      prediction of hard cardiac events (myocardial infarction and cardiac death) has
      been well demonstrated over the last two decades regardless of the absence or
      presence of epicardial CAD. Recently developed semi-conductor, cardiac-dedicated
      cameras allow for decreased acquisition times and systematic procubitus and
      decubitus acquisitions thereby limiting the occurrence of false positives
      historically attributable to artefactual motion, attenuation, and digestive
      artifacts. It is therefore likely that pathophysiological causes rather than
      acquisition artifacts might underlie SPECT perfusion abnormalities. Here, we
      report four representative examples of patients presenting with ischemia in the
      setting of no obstructive CAD and normal fractional flow reserve together with
      elevated IMR and low CFR. The results indicate that ischemia from SPECT MPI could
      result from microvascular dysfunction in patients without obstructive CAD and
      should be considered as a prognostic factor for hard cardiac events.

PMID- 29209951
TI  - Relationship of left ventricular global longitudinal strain with cardiac
      autonomic denervation as assessed by 123I-mIBG scintigraphy in patients with
      heart failure with reduced ejection fraction submitted to cardiac
      resynchronization therapy : Assessment of cardiac autonomic denervation by GLS in
      patients with heart failure with reduced ejection fraction submitted to CRT.
AB  - BACKGROUND: Heart failure (HF) is associated with cardiac autonomic denervation
      (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I
      mIBG) scintigraphy and has prognostic implications. We aimed to study the
      relationship between myocardial contractility assessed by global longitudinal
      strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF.
      METHODS/RESULTS: BETTER-HF is a prospective randomized clinical trial including
      HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are
      submitted to a clinical, echocardiographic, and scintigraphic assessment before
      and 6 months after CRT. 81 pts were included. An echocardiographic response
      (absolute increase in left ventricular ejection fraction >= 10%) was observed in
      73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was
      associated with a better echocardiographic response. There was a significant
      association between late HMR and GLS at baseline and 6 months. At baseline, GLS
      had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of -
      9% maximized the likelihood of correctly classifying a pt as having severe AD
      (HMR < 1.6). CONCLUSION: Myocardial contractility as assessed by GLS is
      moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a
      good discrimination for the identification of severe cardiac denervation. GLS may
      allow for a more readily accessible estimation of the degree of AD in advanced HF
      pts.

PMID- 29209952
TI  - Correction to: SEOM clinical guideline of diagnosis and management of low-grade
      glioma (2017).
AB  - The original version of this article unfortunately contained a mistake. Figure 3
      was incorrect.

PMID- 29209953
TI  - Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to
      microbiological and histopathological tests.
AB  - OBJECTIVE: Tuberculosis (TB) still remains the world's endemic infection. TB
      affects the lungs and any part of the body other than the lung. The diagnosis of
      TB has not changed much over the decades. Ethambutol is one of the first line
      treatments for TB. It can be labeled using 99mTc. 99mTc-ethambutol will be
      accumulated in the site of TB lesion and can be imaged using gamma camera. The
      aim of this study was to evaluate the diagnostic value of 99mTc-ethambutol
      scintigraphy in detecting and localizing of TB. METHODS: Retrospective cross
      sectional study was done. Subjects were patients suspected of having TB
      infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4
      h after injection of 370-555 MBq 99mTc-ethambutol. 99mTc-ethambutol scintigraphy
      was analyzed visually. The results were compared with that of histopathological
      or microbiological tests. Statistical analysis was done to determine the
      sensitivity, specificity, PPV, NPV and accuracy. RESULTS: One hundred and sixty
      eight subjects were involved in this study. There were 110 men and 58 women with
      mean age of 34.52 +/- 11.94 years. There were concordance results in 156 (92.86%)
      and discordant in 12 (7.14%) subjects between 99mTc-ethambutol scintigraphy and
      histopathological or microbiological result. The sensitivity, specificity, PPV,
      NPV and accuracy of 99mTc-ethambutol scintigraphy in the diagnosis of pulmonary
      TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB
      95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9,
      83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in
      this study. CONCLUSION: 99mTc-ethambutol scintigraphy is a useful diagnostic
      imaging technique to detect and localize intra- and extra-pulmonary TB. It is
      safe to be performed even in pediatric patient. Consuming ethambutol less than 2
      weeks did not influence the result.

PMID- 29209954
TI  - QSPR analysis of threshold of odor for the large number of heterogenic chemicals.
AB  - Quantitative structure-property relationships for odor thresholds based on
      representation of the molecular structure by the simplified molecular input-line
      entry system were established using the CORAL software. The total set of
      compounds with numerical data on the so-called arithmetic odor thresholds
      ([Formula: see text]) was distributed into the training and validation sets,
      three times. The average statistical quality of these models is (1) for training
      set [Formula: see text]; and (2) for validation set [Formula: see text]. Thus,
      the predictive potential of this approach was confirmed for three different
      splits into training and validation sets. Domain of applicability and mechanistic
      interpretation of these models are defined from the probabilistic point of view.
      The suggested models are built up according to OECD principles.

PMID- 29209955
TI  - Acalabrutinib: First Global Approval.
AB  - Acerta Pharma is developing the Bruton's tyrosine kinase inhibitor acalabrutinib
      (Calquence(r)) for the treatment of various haematological and solid
      malignancies. The drug has received accelerated approval from the US FDA for the
      treatment of mantle cell lymphoma based on the results of a phase II study, and
      phase III trials in mantle cell lymphoma and chronic lymphocytic leukaemia are
      currently underway. This article summarizes the milestones in the development of
      acalabrutinib leading to this first approval for mantle cell lymphoma.

PMID- 29209956
TI  - Cross-sex genetic correlation does not extend to sexual size dimorphism in
      spiders.
AB  - Males and females are often subjected to different selection pressures for
      homologous traits, resulting in sex-specific optima. Because organismal
      attributes usually share their genetic architectures, sex-specific selection may
      lead to intralocus sexual conflict. Evolution of sexual dimorphism may resolve
      this conflict, depending on the degree of cross-sex genetic correlation (r MF)
      and the strength of sex-specific selection. In theory, high r MF implies that
      sexes largely share the genetic base for a given trait and are consequently
      sexually monomorphic, while low r MF indicates a sex-specific genetic base and
      sexual dimorphism. Here, we broadly test this hypothesis on three spider species
      with varying degrees of female-biased sexual size dimorphism, Larinioides
      sclopetarius (sexual dimorphism index, SDI = 0.85), Nuctenea umbratica (SDI =
      0.60), and Zygiella x-notata (SDI = 0.46). We assess r MF via same-sex and
      opposite-sex heritability estimates. We find moderate body mass heritability but
      no obvious patterns in sex-specific heritability. Against the prediction, the
      degree of sexual size dimorphism is unrelated to the relative strength of same
      sex versus opposite-sex heritability. Our results do not support the hypothesis
      that sexual size dimorphism is negatively associated with r MF. We conclude that
      sex-specific genetic architecture may not be necessary for the evolution of a
      sexually dimorphic trait.

PMID- 29209957
TI  - Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced
      Cirrhotic Rats.
AB  - OBJECTIVE: To evaluate the preventive effect of salvianolate (Sal B) on glucose
      metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats.
      METHODS: Fifty-five Wistar rats were randomly divided into a control group (n=10)
      and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis
      was induced by intraperitoneal administration of DMN. The cirrhotic rats were
      divided into model, Sal B and metformin groups (n=15), respectively. Rats in the
      model group were given saline, two treatment groups were given Sal B (50 mg/kg),
      metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the
      control group were injected 0.9% saline with same volume of vehicle. Body weight
      was measured everyday. Insulin sensitivity was determined by euglycemic
      hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting
      plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline
      (HYP) and liver function were detected at the end of the treatment. Area under
      the curve (AUC) for OGTT was calculated. Liver and pancreas histology were
      determined by histopathological examination with hematoxylin and eosin staining
      (HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic
      expression of alpha-smooth muscle actin (alpha-SMA) and collagen (Col I) were
      evaluated by immunohistochemical staining. RESULTS: Compared with the model
      group, Sal B significantly increased body and liver weight, liver-body ratio,
      glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of
      administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC
      for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level
      (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver
      tissue, suppressing fibrosis progression and inhibiting the expression of alpha
      SMA and Col I in liver. Compared with the metformin group, Sal B had advantages
      in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function
      and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently
      than Sal B (P<0.05). CONCLUSIONS: Sal B could improve glucose metabolism in
      cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin
      sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was
      clinically potential in preventing glucose metabolism anomalies accompanied with
      cirrhosis.

PMID- 29209958
TI  - Moxibustion Therapy in Traditional Mongolian Medicine.
AB  - From the medical history of traditional Eastern Asian and Tibetan medicine, the
      origin and development of moxibustion seems to be closely related to Mongolia. To
      explore the current clinical practice of moxibustion in Mongolia, we visited a
      teaching hospital, the Traditional Medical Science, Technology and Production
      Corporation of Mongolia, in February 2014. Many types of moxibustion are found to
      be used, and various modalities and methods are practiced based on the principles
      of traditional Mongolian medicine. In particular, Mongolian drug moxibustion,
      which uses small butter-warmed bags packed with powdered aromatic herbs instead
      of moxa cones, is a unique moxibustion technique not found in other countries. In
      this paper, we introduce the clinical practice of moxibustion, specifically
      Mongolian drug moxibustion in Mongolia.

PMID- 29209959
TI  - Improving the Level and Quality of Ethics Review in Chinese Medicine and
      Integrative Medicine.
AB  - Three features of ethics review in Chinese medicine (CM) and integrative medicine
      (IM) were put forward in this paper. It is consistent with the principles of
      ethical review in Western medicine; it has to be compliant with the laws of CM
      and IM; emphasis should be laid on the review of clinical practice facts and
      experience. Three problems were pointed out. The characteristics of CM and IM are
      not distinctive enough, operation procedures need to be refined and effectiveness
      remains to be improved. Based on the mentioned above, seven measures were
      proposed to improve the level and quality of ethics review in CM and IM,
      including better brand awareness, considerable tolerance, treatment based on
      disease differentiation and syndrome differentiation, scientific review and
      toxicity and side effects of CM, perfection of the ethics review system,
      reasonable procedures of ethics review and more specialized ethics review
      workers.

PMID- 29209960
TI  - Systematic Reviews/Meta-Analyses of Integrative Medicine in Chinese Need
      Regulation and Monitoring Urgently and Some Suggestions for Its Solutions.
AB  - With the introduction and development of evidence-based medicine in China, it has
      been spread rapidly in the area of integrative medicine (IM) and has become a new
      unique discipline. During almost 20 years, as one of the most important parts of
      evidence-based IM, systematic review (SR)/meta-analysis (MA) of IM have shown a
      good development momentum in the aspects of quantity, depth, breadth and
      influence, but also face the harsh situation of the uncontrolled quantity and
      quality, especially for SRs in Chinese. Therefore, how to supervise and
      standardize this area effectively becomes a problem to be solved. Based on the
      experience both at home and abroad, the authors put forward several kinds of
      solutions for laying the foundation for further development such as promoting the
      registration system of SR/MA of IM, effectively setting up the regulatory
      platform of quality and quantity, launching professional training for SR/MA
      reviewers, forming qualification registration, developing the data transfer and
      sharing platform to realize the transparency of evidence process.

PMID- 29209961
TI  - Finite element analysis of the wrist in stroke patients: the effects of hand
      grip.
AB  - The provision of the most suitable rehabilitation treatment for stroke patient
      remains an ongoing challenge for clinicians. Fully understanding the
      pathomechanics of the upper limb will allow doctors to assist patients with
      physiotherapy treatment that will aid in full arm recovery. A biomechanical study
      was therefore conducted using the finite element (FE) method. A three-dimensional
      (3D) model of the human wrist was reconstructed using computed tomography (CT)
      scanned images. A stroke model was constructed based on pathological problems,
      i.e. bone density reductions, cartilage wane, and spasticity. The cartilages were
      reconstructed as per the articulation shapes in the joint, while the ligaments
      were modelled using linear links. The hand grip condition was mimicked, and the
      resulting biomechanical characteristics of the stroke and healthy models were
      compared. Due to the lower thickness of the cartilages, the stroke model reported
      a higher contact pressure (305 MPa), specifically at the MC1-trapezium.
      Contrarily, a healthy model reported a contact pressure of 228 MPa. In the
      context of wrist extension and displacement, the stroke model (0.68 degrees  and
      5.54 mm, respectively) reported a lower magnitude than the healthy model (0.98
      degrees  and 9.43 mm, respectively), which agrees with previously reported works.
      It was therefore concluded that clinicians should take extra care in
      rehabilitation treatment of wrist movement in order to prevent the occurrence of
      other complications. Graphical abstract ?.

PMID- 29209962
TI  - Effects of location and extent of spine clustering on synaptic integration in
      striatal medium spiny neurons-a computational study.
AB  - The nucleus accumbens (NAc) is known widely for its role in the reward circuit,
      which is dysregulated in a number of psychological disorders. Recent evidence
      also suggests the contribution of this structure in spatial and gustatory
      memories. Because of its role in different types of memories, similar to the
      hippocampus, we assumed the formation of spine clusters, which are engrams of
      memory, to be present on dendrites of medium spiny neurons (MSNs). We found that
      the activation of clustered inputs resulted in sublinear summation when clusters
      were present on the same branch and also when inputs were distributed on
      different branches. The size, as well as the location of clusters, was found to
      affect the summation. With an increase in cluster size and distance from soma,
      the summation was increasingly sublinear. When the temporal integration window
      was measured for clustered spines, it was found to be narrower as compared to
      that for a single spine. Also, distally located clusters resulted in a wider
      temporal window, as compared to proximal clusters. Our results suggest that
      depending on the location of clusters, the modes of integration will differ in
      MSNs possessing clustered spines.

PMID- 29209963
TI  - Generation of highly potent organic fertilizer from pernicious aquatic weed
      Salvinia molesta.
AB  - Utilization of Salvinia molesta, an aquatic weed which is notorious for its
      allelopathy and invasiveness, has been explored by its vermicomposting. Fourier
      transform infrared spectroscopy (FT-IR) and plant bioassay tests were conducted
      to analyze the composition and fertilizer value of S .molesta vermicompost.
      Germination and seedling growth tests were performed in soil supplemented with
      vermicompost at levels ranging from 0.75 to 40% by weight of the soil on three
      common food plants, ladies finger (Abelmoschus esculentus), cucumber (Cucumis
      sativus), and green gram (Vigna radiata). The influence of S. molesta's
      vermicompost on some of the physicochemical and biological attributes of the soil
      was also studied. FT-IR analysis revealed that S. molesta loses its allelopathy,
      as the chemical compounds that are responsible for it are largely destroyed, in
      the course of its vermicomposting. There is also an indication that a portion of
      lignin content of S. molesta is degraded. Vermicompost enhanced the germination
      success and promoted the morphological growth and biochemical content of the
      plant species studied. It also bestowed plant friendly physicochemical and
      biological attributes to the soil. The findings raise the prospect that billions
      of tons of S. molesta biomass-which not only goes to waste at present but is also
      a cause of serious harm to the environment-may become utilizable in organic
      agriculture.

PMID- 29209964
TI  - Probing the toxicity mechanism of multiwalled carbon nanotubes on bacteria.
AB  - Carbon nanotubes (CNTs) have emerged recently as superior adsorbent materials for
      the removal of recalcitrant pollutants. The potential of combining the sorption
      capability of CNTs with bacterial degradation for pollutant removal, however,
      necessitates further investigation of the mechanisms of CNTs' toxicity towards
      bacterial cells. In this study, we used a panel of stress-responsive recombinant
      Escherichia coli bioluminescence bacterial strains to explore the possible
      mechanisms of toxicity of multiwalled carbon nanotubes (MWCNTs). The effects of
      MWCNTs on markers of oxidative stress, protein, DNA, and membrane damage enabled
      the exposition of some of the mechanisms of their antimicrobial properties. Using
      both a bioluminescence bioreporter panel and live/dead staining, we observed that
      membrane damage played a role in the toxicity of MWCNTs. A subsequent viability
      study using three strains of bacteria-two gram-negative (Escherichia coli,
      Pseudomonas aeruginosa) and one gram-positive (Bacillus subtilis)-showed
      significant MWCNT toxicity in hypotonic water and phosphate-buffered saline
      solution, compared with the MWCNT toxicity towards the same bacteria incubated in
      isotonic-rich media. Using a field-emission scanning electron microscope, we
      demonstrated that membrane damage is caused largely by MWCNTs trapping bacteria
      and piercing the cell walls. As a result of our observations, we propose
      integrating MWCNTs and bacteria degradation for pollutant removal in nutrient
      rich media to minimize the toxicity effect of CNTs.

PMID- 29209965
TI  - Does the air condition system in busses spread allergic fungi into driver space?
AB  - The aim of this study was to establish whether the air-conditioning system in
      buses constitutes an additional source of indoor air contamination with fungi,
      and whether or not the fungi concentration depends on the period from the last
      disinfection of the system, combined with replacement of the cabin dust particle
      filter. The air samples to fungi analysis using impact method were taken in 30
      buses (20 with an air-conditioning system, ACS; 10 with a ventilation system, VS)
      in two series: 1 and 22 weeks after cabin filter replacement and disinfection of
      the air-conditioning system. During one test in each bus were taken two samples:
      before the air-conditioning or ventilation system switched on and 6 min after
      operating of these systems. The atmospheric air was the external background (EB).
      After 1 week of use of the system, the fungi concentrations before starting of
      the ACS and VS system were 527.8 and 1053.0 cfu/m3, respectively, and after 22
      weeks the concentrations were 351.9 and 1069.6 cfu/m3, respectively. While in the
      sample after 6 min of ACS and VS system operating, the fungi concentration after
      1 week of use was 127.6 and 233.7 cfu/m3, respectively, and after 22 weeks it was
      113.3 and 324.9 cfu/m3, respectively. Results do not provide strong evidence that
      air-conditioning system is an additional source of indoor air contamination with
      fungi. A longer operation of the system promoted increase of fungi concentration
      in air-conditioned buses only.

PMID- 29209966
TI  - Residue behavior and risk assessment of imidacloprid applied on greenhouse
      cultivated strawberries under different application conditions.
AB  - A risk assessment for imidacloprid applied on strawberries under different
      conditions was performed after residue determination using the quick, cheap,
      effective, rugged, and safe (QuEChERS) method. The application conditions were
      varied according to the applied dosage, addition of a plant oil or organosilicon
      surfactant, water volume, and sprayer type. The degradation dynamics of
      imidacloprid on strawberries followed first-order kinetics. At applied doses of
      30-60 g a.i. ha-1, the half-lives of imidacloprid were 2.89-3.46, 1.98-3.65, and
      2.57-2.77 days after application without a surfactant or with a plant oil or
      organosilicon surfactant, respectively. For water volumes of 112.5, 225, 450,
      675, and 900 L ha-1, the half-lives of imidacloprid applied in the presence of
      the plant oil surfactant were 3.30, 7.70, 5.33, 7.70, and 6.30 days,
      respectively. The half-lives after application with a knapsack mist duster,
      electric sprayer, and manual sprayer were 2.16, 5.77, and 7.70 days,
      respectively. The health risk assessment revealed risk quotients less than 1 in
      all cases, indicating that the application of imidacloprid poses a low health
      risk to humans after a pre-harvest interval of 10 days under our application
      conditions. The risk assessment results can provide reference data for setting a
      reasonable maximum residue limit for imidacloprid on strawberries in China.

PMID- 29209967
TI  - Cumulative impacts from multiple human activities on seagrass meadows in eastern
      Mediterranean waters: the case of Saronikos Gulf (Aegean Sea, Greece).
AB  - Ecosystem-based management (EBM) addresses the fundamental need to account for
      cumulative impacts of human activities with the aim of sustainably delivering
      ecosystem services. The Saronikos Gulf, a large embayment of the Aegean Sea,
      provides a wide range of ecosystem services that are impacted by multiple human
      activities, deriving from the metropolitan area of Athens (situated at the
      northeast part of the Gulf). The anthropogenic impacts affect the status of
      several marine ecosystem components, e.g., seagrass meadows. Cymodocea nodosa
      meadows are only present at the most confined western part of the Gulf, whereas
      Posidonia oceanica meadows are mainly distributed in the inner and outer part of
      the Gulf. The aim of this study is to assess the cumulative impacts from multiple
      human activities on the seagrass meadows in the Gulf. The main results indicated
      that most impacted meadows are P. oceanica in the inner part of the Gulf,
      adjacent to the most urbanized coastal areas, and near port infrastructures. Land
      based pollution, as well as physical damage and loss seem to be the main
      pressures exerted on the meadows. Understanding cumulative impacts is crucial for
      informing policy decisions under an EBM approach.

PMID- 29209968
TI  - The impact of internet use on air pollution: Evidence from emerging countries.
AB  - The goal of this study is to analyze the impact of Internet use, employed as a
      proxy for information and communications technologies (ICTs), on CO2 emissions.
      Using a panel of 20 emerging economies spanning the period 1990 to 2015, this
      paper finds that increased Internet access results in lower levels of air
      pollution. Moreover, panel causality test results highlight a unidirectional
      causality running from Internet use to CO2 emissions. This result also has
      crucial policy implications for the governments in emerging markets. For
      instance, increased investment in the ICT sector could be a plausible channel to
      reduce air pollution level.

PMID- 29209969
TI  - Children's environmental chemical exposures in the USA, NHANES 2003-2012.
AB  - Children are vulnerable to environmental chemical exposures, but little is known
      about the extent of multiple chemical exposures among children. We analyzed
      biomonitoring data from five cycles (2003-2012) of the National Health and
      Nutrition Examination Survey (NHANES) to describe multiple chemical exposures in
      US children, examine levels of chemical concentrations present over time, and
      examine differences in chemical exposures by selected demographic groups. We
      analyzed data for 36 chemical analytes across five chemical classes in a sample
      of 4299 children aged 6-18. Classes included metals, pesticides, phthalates,
      phenols, and polycyclic aromatic hydrocarbons. We calculated the number and
      percent of chemicals detected and tested for secular trends over time in chemical
      concentrations. We compared log concentrations among groups defined by age, sex,
      race/ethnicity, and poverty using multiple linear regression models and report
      adjusted geometric means. Among a smaller subgroup of 733 children with data
      across chemical classes, we calculated the linear correlations within and between
      classes and conducted a principal component analysis. The percentage of children
      with detectable concentrations of an individual chemical ranged from 26 to 100%;
      the average was 93%, and 29 of 36 were detected in more than 90% of children.
      Concentrations of most tested chemicals were either unchanged or declined from
      earlier to more recent years. Many differences in concentrations were present by
      age, sex, poverty, and race/ethnicity categories. Within and between class
      correlations were all significant and positive, and the principal component
      analysis suggested a one factor solution, indicating that children exposed to
      higher levels of one chemical were exposed to higher levels of other chemicals.
      In conclusion, children in the USA are exposed to multiple simultaneous chemicals
      at uneven risk across socioeconomic and demographic groups. Further efforts to
      understand the effects of multiple exposures on child health and development are
      warranted.

PMID- 29209970
TI  - Haze and health impacts in ASEAN countries: a systematic review.
AB  - Seasonal haze episodes and the associated inimical health impacts have become a
      regular crisis among the ASEAN countries. Even though many emerging experimental
      and epidemiological studies have documented the plausible health effects of the
      predominating toxic pollutants of haze, the consistency among the reported
      findings by these studies is poorly understood. By addressing such gap, this
      review aimed to critically highlight the evidence of physical and psychological
      health impacts of haze from the available literature in ASEAN countries.
      Systematic literature survey from six electronic databases across the
      environmental and medical disciplines was performed, and 20 peer-reviewed studies
      out of 384 retrieved articles were selected. The evidence pertaining to the
      health impacts of haze based on field survey, laboratory tests, modelling and
      time-series analysis were extracted for expert judgement. In specific, no
      generalization can be made on the reported physical symptoms as no specific
      symptoms recorded in all the reviewed studies except for throat discomfort.
      Consistent evidence was found for the increase in respiratory morbidity,
      especially for asthma, whilst the children and the elderly are deemed to be the
      vulnerable groups of the haze-induced respiratory ailments. A consensual
      conclusion on the association between the cardiovascular morbidity and haze is
      unfeasible as the available studies are scanty and geographically limited albeit
      of some reported increased cases. A number of modelling and simulation studies
      demonstrated elevating respiratory mortality rates due to seasonal haze exposures
      over the years. Besides, evidence on cancer risk is inconsistent where industrial
      and vehicular emissions are also expected to play more notable roles than mere
      haze exposure. There are insufficient regional studies to examine the association
      between the mental health and haze. Limited toxicological studies in ASEAN
      countries often impede a comprehensive understanding of the biological mechanism
      of haze-induced toxic pollutants on human physiology. Therefore, the lack of
      consistent evidence among the reported haze-induced health effects as highlighted
      in this review calls for more intensive longitudinal and toxicological studies
      with greater statistical power to disseminate more reliable and congruent
      findings to empower the institutional health planning among the ASEAN countries.

PMID- 29209971
TI  - Synergistic phytoremediation of wastewater by two aquatic plants (Typha
      angustifolia and Eichhornia crassipes) and potential as biomass fuel.
AB  - The ability of a mixture of Typha angustifolia and Eichhornia crassipes to remove
      organics, nutrients, and heavy metals from wastewater from a Thailand fresh
      market was studied. Changes in physicochemical properties of the wastewater
      including pH, temperature, chemical oxygen demand, dissolved oxygen, biochemical
      oxygen demand (BOD), total P, TOC, conductivity, total Kjeldahl nitrogen, NO3--N,
      NH3-N, and metal (Pb, Cd, and Zn) concentrations were monitored. In the aquatic
      plant (AP) treatment, 100% survival of both species was observed. Dry biomass
      production and growth rate of T. angustifolia were approximately 3.3* and 2.7* of
      those for E. crassipes, respectively. The extensive root system of the plants
      improved water quality as determined by a marked decrease in turbidity in the AP
      treatment after 7 days. BOD content served as a useful indicator of water
      quality; BOD declined by 91% over 21 days. Both T. angustifolia and E. crassipes
      accumulated similar quantities of metals in both roots and shoots. Accumulation
      of metals was as follows: Zn > Cd > Pb. A study of calorific value and biomass
      composition revealed that T. angustifolia and E. crassipes possessed similar
      carbon content (~ 35%), hydrogen content (~ 6%), and gross calorific value. E.
      crassipes contained up to 16.9% ash and 65.4% moisture. Both species are
      considered invasive in Thailand; however, they may nonetheless provide practical
      benefits: In addition to their combined abilities to treat wastewater, T.
      angustifolia holds potential as an alternative energy source due to its high
      biomass production.

PMID- 29209972
TI  - PBPK/PD assessment for Parkinson's disease risk posed by airborne pesticide
      paraquat exposure.
AB  - Exposure to several specific pesticides has led to an increase of Parkinson's
      disease (PD) risk. However, it is difficult to quantify the PD population risk
      related to certain pesticides in regions where environmental exposure data are
      scarce. Furthermore, the time trend of the prevalence and incidence of PD
      embedded in the background relationship between PD risk and pesticide exposures
      has not been well characterized. It has been convincingly identified that a key
      pesticide associated significantly with an increased risk trend of PD is paraquat
      (PQ). Here, we present a novel, probabilistic population-based exposure-response
      approach to quantify the contribution from PQ exposure to prevalence risk of PD.
      We found that the largest PQ exposure contributions occurred in its positive
      trend during 2004-2011, with the PQ contributing nearly 21 and 24%, respectively,
      to the PD prevalence rates among the age groups of 70-79 and >= 80 years in
      Taiwan. We also employed the present population risk model to predict the PQ
      induced PD prevalence based on the projected rates of increase in PQ exposure
      associated with age-specific population. The predicted outcome can be used as an
      early warning signal for public health authorities. We suggest that a mechanistic
      understanding of the contribution of a specific pesticide exposure to PD risk
      trends is crucial to enhance our insights into the perspective on the impacts of
      environmental exposure on the neurodegenerative diseases.

PMID- 29209973
TI  - Insight into litter decomposition driven by nutrient demands of symbiosis system
      through the hypha bridge of arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal fungi (AMF) play an important role in litter
      decomposition. This study investigated how soil nutrient level affected the
      process. Results showed that AMF colonization had no significant effect on litter
      decomposition under normal soil nutrient conditions. However, litter
      decomposition was accelerated significantly under lower nutrient conditions. Soil
      microbial biomass in decomposition system was significantly increased.
      Especially, in moderate lower nutrient treatment (condition of half-normal soil
      nutrient), litters exhibited the highest decomposition rate, AMF hypha revealed
      the greatest density, and enzymes (especially nitrate reductase) showed the
      highest activities as well. Meanwhile, the immobilization of nitrogen (N) in the
      decomposing litter remarkably decreased. Our results suggested that the roles AMF
      played in ecosystem were largely affected by soil nutrient levels. At normal soil
      nutrient level, AMF exhibited limited effects in promoting decomposition. When
      soil nutrient level decreased, the promoting effect of AMF on litter
      decomposition began to appear, especially on N mobilization. However, under
      extremely low nutrient conditions, AMF showed less influence on decomposition and
      may even compete with decomposer microorganisms for nutrients.

PMID- 29209974
TI  - Metallothionein in Hermetia illucens (Linnaeus, 1758) larvae (Diptera:
      Stratiomyidae), a potential biomarker for organic waste system.
AB  - Black soldier fly, Hermetia illucens (Linnaeus, 1758), is an important economic
      fly as its larvae can be used for recycling organic waste, such as food waste and
      manure. H. illucens larvae (BSFL) could uptake Cd from substrates and accumulate
      it inside bodies, which need to be monitored during waste treatment.
      Metallothionein (MT) usually serve as biomarker because of its role in metal
      homeostasis, detoxification, and dose response of heavy metals. Therefore, a MT
      gene was cloned from H. illucens (HIMT) that encoded 40 amino acids with typical
      cysteine rich features, which had a high sequence identity with other insect MTs.
      The expression of HIMT and total MT protein was measured in BSFL fed by meals
      spiked with gradient dose of Cd (0, 5, 50, 500 mg/kg) for 24, 48, 72, and 96 h,
      respectively. Dose-associated response of HIMT and total MT were found and the
      possible correlative range of Cd was from 5 to 50 mg/kg. The expression of HIMT
      might be a potential biomarker for monitoring Cd contamination by H. illucens in
      terrestrial organic matters, which might further apply in waste transformation
      system.

PMID- 29209975
TI  - Commercial silicate phosphate sequestration and desorption leads to a gradual
      decline of aquatic systems.
AB  - Laboratory desorption behaviour, function and elemental composition of
      commercially marketed silicate minerals used to sequester phosphorus pollution as
      well as Zeolite, Smectite, and Kaolinite were determined to see whether their use
      by environmental scientists and water managers in eutrophic waterways has the
      potential to contribute to longer-term environmental impacts. As expected, lower
      phosphorus concentrations were observed, following treatment. However, data
      relating to desorption, environmental fate and bioavailability of phospho
      silicate complexes (especially those containing rare earth elements) appear to be
      underrepresented in product testing and trial publications. Analysis of
      desorption of phosphate (P) was > 5 MUg[P]/L for all three non-commercial samples
      and 0 > MUg[P]/L > 5 for all commercial silicates for a range of concentrations
      from 0 to 300 MUg[P]/L. Based on a review of bioaccumulation data specific to the
      endangered Cherax tenuimanus (Hairy Marron) and other endemic species, this is
      significant considering anything > 20 MUg[La]/L is potentially lethal to the
      hairy marron, other crustaceans and even other phyla. Where prokaryotic and
      eukaryotic effects are underreported, this represents a significant challenge.
      Especially where product protocols recommend continual reapplication, this is
      significant because both the forward and reverse reactions are equally important.
      The users of silicate minerals in water columns should accept the dynamic nature
      of the process and pay equal attention to both adsorption and desorption because
      desorption behaviour is an inherent trait. Even if broader desorption
      experimentation is difficult, expensive and time-consuming, it is a critical
      consideration nonetheless.

PMID- 29209977
TI  - Impact of oral cadmium intoxication on levels of different essential trace
      elements and oxidative stress measures in mice: a response to dose.
AB  - The study evaluated the effect of oral intoxication of cadmium and the possible
      causes of oxidative stress and its preferential accumulation in different organs
      as well as sub-sequential effects in mice. Twenty-four Swiss albino male mice
      were divided into three groups viz., normal control group without cadmium
      chloride (CdCl2), whereas a daily dose of 0.5 and 1.2 mg of CdCl2 was orally
      administered for a period of a week to dose group 1 (DG-1) and dose group 2 (DG
      2), respectively. A significant increase in the severity of cadmium toxicity was
      observed in animals as evidenced by aggravation in liver enzymes viz., serum
      alanine aminotransferase and aspartate transaminase, whereas lower levels of
      antioxidative stress markers in liver and kidney tissues of treated mice were
      observed as compared to normal control group. A significant depletion of calcium
      levels in liver tissues of DG-1 (217.36 +/- 1.73 MUg/g of wet tissues) and DG-2
      (186.41 +/- 1.56 MUg/g of wet tissues) groups, along with Cd accumulation, was
      observed. To summarize, the current study would increase our understanding with
      respect to dose-dependent absorption of Cd and its toxicity led to mortality as
      well as adverse health effects in the body of mice. Graphical abstract ?.

PMID- 29209976
TI  - Do cemeteries emit drugs? A case study from southern Germany.
AB  - The risk of earth burials for the environment and public health is a matter of
      controversial debate. The aim of the present study is to characterise the
      drainage of cemeteries with regard to the concentration of a number of
      pharmaceuticals and to the soil's hydrochemical properties, and to discuss these
      data in comparison with data obtained for surface waters located upstream of the
      cemeteries. Of the 12 drainage samples analysed using LC-ESI-MS/MS, seven
      contained carbamazepine (< 225 ng l-1), five contained hydrochlorothiazide, one
      contained metoprolol (23 ng l-1) and one contained traces of ibuprofen. The
      surface water samples contained a larger number of different drugs (8 of the 12
      drugs under investigation) and higher concentrations (e.g. metropolol 2230 ng l
      1). The NO3, NH4, PO4 and DOC concentrations and the electrical conductivity of
      the cemetery drainages were in several samples higher than those of the surface
      water samples. The NO3 and NH4 concentrations exceeded the legal contaminant
      limits of drinking water in only one case. The present study found that the
      release of drugs and nutrients from cemeteries, measured in surface water drug
      loads, presents a low environmental risk. However, the study is only a snapshot
      and long-term monitoring of cemetery drainages, including a broad range of
      pharmaceuticals and detailed hydrological investigations, will have to be carried
      out before more substantiated statements can be made.

PMID- 29209978
TI  - Bioengineered silver nanoparticles as potent anti-corrosive inhibitor for mild
      steel in cooling towers.
AB  - Silver nanoparticle-aided enhancement in the anti-corrosion potential and
      stability of plant extract as ecologically benign alternative for microbially
      induced corrosion treatment is demonstrated. Bioengineered silver nanoparticles
      (AgNPs) surface functionalized with plant extract material (proteinacious) was
      generated in vitro in a test tube by treating ionic AgNO3 with the leaf extract
      of Azadirachta indica that acted as dual reducing as well as stabilizing agent.
      Purity and crystallinity of the AgNPs, along with physical and surface
      characterizations, were evaluated by performing transmission electron microscopy,
      Fourier transform infrared spectroscopy, energy dispersive x-ray spectra, single
      area electron diffractions, zeta potential, and dynamic light scattering
      measurements. Anti-corrosion studies against mild steel (MS1010) by corrosion
      inducive bacterium, Bacillus thuringiensis EN2 isolated from cooling towers, were
      evaluated by performing electrochemical impedance spectroscopy (EIS), weight loss
      analysis, and surface analysis by infrared spectroscopy. Our studies revealed
      that AgNPs profoundly inhibited the biofilm on MS1010 surface and reduced the
      corrosion rates with the CR of 0.5 mm/y and an inhibition efficiency of 77% when
      compared to plant extract alone with a CR of 2.2 mm/y and an inhibition
      efficiency of 52%. Further surface analysis by infrared spectra revealed that
      AgNPs formed a protective layer of self-assembled film on the surface of MS1010.
      Additionally, EIS and surface analysis revealed that the AgNPs have inhibited the
      bacterial biofilm and reduced the pit on MS1010. This is the first report
      disclosing the application of bioengineered AgNP formulations as potent anti
      corrosive inhibitor upon forming a protective layer over mild steel in cooling
      water towers. Graphical Abstract ?.

PMID- 29209979
TI  - Genotoxicity assessment of raw and treated water samples using Allium cepa assay:
      evidence from Perak River, Malaysia.
AB  - Allium cepa assay was carried out in this study to evaluate genotoxic effects of
      raw and treated water samples from Perak River in Perak state, Malaysia. Samples
      were collected from three surface water treatment plants along the river, namely
      WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions)
      bulbs, 25-30 mm in diameter and average weight of 20 g, were set up in distilled
      water for 24 h at 20 +/- 2  degrees C and protected from direct sunlight, to let
      the roots to grow. After germination of roots (0.5-1.0 cm in length), bulbs were
      transferred to collected water samples each for a 96-h period of exposure. The
      root physical deformations were observed. Genotoxicity quantification was based
      on mitotic index and genotoxicity level. Statistical analysis using cross
      correlation function for replicates from treated water showed that root length
      has inverse correlation with mitotic indices (r = - 0.969) and frequencies of
      cell aberrations (r = - 0.976) at lag 1. Mitotic indices and cell aberrations of
      replicates from raw water have shown positive correlation at lag 1 (r = 0.946).
      Genotoxicity levels obtained were 23.4 +/- 1.98 (WTPP), 26.68 +/- 0.34 (WTPS),
      and 30.4 +/- 1.13 (WTPK) for treated water and 17.8 +/- 0.18 (WTPP), 37.15 +/-
      0.17 (WTPS), and 47.2 +/- 0.48 (WTPK) for raw water. The observed cell
      aberrations were adherence, chromosome delay, C-metaphase, chromosome loss,
      chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated
      nuclei. The morphogenetic deformations obtained were likely due to genotoxic
      substances presence in collected water samples. Thus, water treatment in Malaysia
      does not remove genotoxic compounds.

PMID- 29209980
TI  - Predictors of Increased Length of Hospital Stay Following Laparoscopic Sleeve
      Gastrectomy from the National Surgical Quality Improvement Program.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy is the most commonly performed
      bariatric procedure in the USA. Identifying preoperative risk factors for
      prolonged postoperative hospital stay will help appropriately select patients for
      fast-track protocols and avoid costly readmissions. To date, there has been no
      large national database analysis of risk factors for prolonged length of stay
      following laparoscopic sleeve gastrectomy. METHODS: Laparoscopic sleeve
      gastrectomy procedures reported to the American College of Surgeons National
      Surgical Quality Improvement Program between 2009 and 2012 were reviewed. Open
      procedures and revisional procedures were excluded. Baseline patient
      characteristics and preoperative lab values were reviewed. Univariate analysis
      was conducted to identify patient factors that predicted prolonged
      hospitalization (defined as >= 3 days). Multivariate logistic regression was used
      to identify factor associated with prolonged length of stay. RESULTS: We
      identified 11,430 patients who underwent laparoscopic sleeve gastrectomy. The
      median length of stay was 2 days and 18.4% required hospitalization >= 3 days.
      Multivariate analysis revealed that female sex, age greater than 65, body mass
      index greater than 50, chronic obstructive pulmonary disease, hypertension, renal
      insufficiency, anemia, and prolonged operative time were significantly associated
      with prolonged hospital stay. CONCLUSIONS: Preoperative patient characteristics
      as well as operative details predict prolonged length of stay following
      laparoscopic sleeve gastrectomy. As the utilization of fast-track protocols in
      bariatric surgery programs expands, these data may be used to assist in the
      selection of patients who may be inappropriate for rapid discharge from the
      hospital after sleeve gastrectomy as well as guide medical optimization
      strategies preoperatively.

PMID- 29209981
TI  - The Effect of Frailty Index on Early Outcomes after Combined Colorectal and Liver
      Resections.
AB  - BACKGROUND: Although previous studies have examined frailty as a potential
      predictor of adverse surgical outcomes, little is reported on its application. We
      sought to assess the impact of the 5-item modified frailty index (mFI) on
      morbidity in patients undergoing combined colorectal and liver resections.
      METHODS: Adult patients who underwent combined colorectal and liver resections
      were identified using the ACS-NSQIP database (2005-2015). The 5-item mFI consists
      of history of chronic obstructive pulmonary disease, congestive heart failure,
      hypertension, diabetes, and partial/total dependence. Patients were stratified
      into three groups: mFI 0, 1, or >= 2. The impact of the mFI on primary outcomes
      (30-day overall and serious morbidity) was assessed using multivariable logistic
      regression. Subgroup analyses by age and hepatectomy type was also performed.
      RESULTS: A total of 1928 patients were identified: 55.1% with mFI = 0, 33.2% with
      mFI = 1, and 11.7% with mFI >= 2. 75.9% of patients underwent wedge
      resection/segmentectomy (84.6% colon, 15.4% rectum), and 24.1% underwent
      hemihepatectomy (88.8% colon, 11.2% rectum). On unadjusted analysis, patients
      with mFI >= 2 had significantly greater rates of overall and serious morbidity,
      regardless of age and hepatectomy type. These findings were consistent with the
      multivariable analysis, where patients with mFI >= 2 had increased odds of
      overall morbidity (OR 1.41, 95% CI 1.02-1.96, p = 0.037) and were more than twice
      likely to experience serious morbidity (OR 2.12, 95% CI 1.47-3.04, p < 0.001).
      CONCLUSIONS: The 5-item mFI is significantly associated with 30-day morbidity in
      patients undergoing combined colorectal and liver resections. It is a tool that
      can guide surgeons preoperatively in assessing morbidity risk in patients
      undergoing concomitant resections.

PMID- 29209982
TI  - Adherence to Inhaled Medications and its Effect on Healthcare Utilization and
      Costs Among High-Grade Chronic Obstructive Pulmonary Disease Patients.
AB  - BACKGROUND: Adherence to inhaled medication regimens affects chronic obstructive
      pulmonary disease (COPD) prognosis and quality of life, and reduces the use of
      healthcare services, resulting in cost savings. OBJECTIVES: To examine the
      effects of adherence to inhaled medication regimens on healthcare utilization and
      costs in high-grade COPD patients. METHODS: We performed an observational
      retrospective cohort study using a longitudinal data set from the Korean Health
      Insurance Review and Assessment Service (2008-2013) containing healthcare
      services' information for 50 million beneficiaries. The study population was high
      grade COPD patients. "Adherent" was defined as a patient attaining a medication
      possession ratio (MPR) >= 80%. We estimated the effects of adherence on the use
      of intensive care units (ICUs) and emergency rooms (ERs) using a multivariate
      logistic regression, and estimated the effects on costs (all-cause and COPD
      related) using a generalized linear model, with adjustment for patient
      sociodemographic characteristics, health status, and comorbidities. RESULTS: Of
      9086 high-grade COPD patients, adherence declined from 34.7 to 22.3% over 4
      years. Adherence was inversely associated with use of ICUs and costs, and this
      association got stronger as the adherence period lengthened. Over the 4-year
      period, the adherent group had a lower likelihood of using ICUs [odds ratio (OR)
      = 0.74, 95% confidence interval (CI) 0.60-0.91] than the non-adherent group.
      Similarly, the adherent group had a 10.4% lower all-cause cost (p < 0.001) and an
      11.7% lower COPD-related cost (p < 0.0001) versus the non-adherent group.
      CONCLUSIONS: Adherence reduces healthcare utilization and costs, so adherence is
      not only clinically effective but also economically efficient. However, less than
      one-quarter of this population remained adherent over the 4-year period,
      suggesting that strategies are needed to improve adherence.

PMID- 29209983
TI  - Vibralactone Biogenesis-Associated Analogues from Submerged Cultures of the
      Fungus Boreostereum vibrans.
AB  - A scale-up fermentation of the fungus Boreostereum vibrans facilitated the
      isolation of six new vibralactone biogenesis-associated analogues, namely
      vibralactamide A (1), vibralactone T (2), 13-O-lactyl vibralactone (3), 10-O
      acetyl vibralactone G (4), (11R,12R)- and (11S,12R)-vibradiol (5, 6). Their
      structures were established via extensive spectroscopic analyses, specific
      optical rotation comparison, and Snatzke's method. The biosynthetic pathway for
      vibralactamide A was postulated. The absolute configuration of vibralactone B was
      revised by single crystal X-ray diffraction analysis. This work puts the
      divergent vibralactone biosynthesis pathway one step further and expands the
      structural diversity of vibralactone-associated compounds.

PMID- 29209985
TI  - Frequent and Yet Unreported GNAQ and GNA11 Mutations are Found in Uveal
      Melanomas.
AB  - Malignant melanoma of the uvea is the most common primary malignant tumor in the
      eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using
      formalin-fixed, paraffin-embedded material and correlate the results with
      clinicopathological parameters. Tumor tissue was microdissected followed by
      amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by
      Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet
      unreported, were found. Two cases showed multiple mutations. Overall survival was
      significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In
      concordance with previous studies, high frequencies of mutations in GNAQ or GNA11
      were detected. Interestingly, in about 20% of UM, not yet reported mutations in
      GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in
      GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation
      analysis in routine diagnostic procedures might be helpful for future therapeutic
      decisions.

PMID- 29209984
TI  - Intravesical Thalidomide boosts bacillus Calmette-Guerin (BCG) in non-muscle
      invasive bladder cancer treatment.
AB  - The aim of this study was to explore the efficacy of intravesical Thalidomide
      (immunomodulatory, anti-inflammatory and anti-angiogenic) added to BCG using an
      immune competent autochthonous orthotopic NMIBC animal model. Female Fischer 344
      rats, 7 weeks of age, received every 2 weeks for four times, a dose of 1.5 mg/kg
      of N-methyl-N-nitrosourea (MNU) intravesically. The rats were randomized into
      four groups (n = 10 per group) to receive intravesical treatment once a week for
      6 weeks as follows: control (0.2 ml vehicle), BCG (2 * 106 CFU of Connaught
      strain in 0.2 ml), Thalidomide (20 mg/kg in 0.2 ml) and BCG-Thalidomide in 0.2
      ml. At week 15, bladders were collected for histopathology, cell turnover index
      by immunohistochemistry and immunoblotting quantification of 4E-BP1 and p70S6K1
      for downstream mTOR proliferation signaling and HIF and VEGF for angiogenesis
      pathway. Thalidomide-BCG association showed a trend for normal histopathology and
      down-regulation of cell turnover, p70S6K1, HIF-1 and VEGF. 4E-BP1 was up
      regulated by treatment, especially in the Thalidomide groups, supporting that its
      regulation occurs independently of p70S6K1 on mTOR pathway in NMIBC. Intravesical
      BCG-Thalidomide might represent a significant increment in NMIBC treatment,
      suggesting p70S6K1, HIF-1 and VEGF as potential molecular target candidates in a
      clinically relevant immune competent NMIBC model.

PMID- 29209986
TI  - Data on Single Nucleotide Polymorphism of DNA Repair Genes and Breast Cancer Risk
      from Poland.
AB  - Single nucleotide polymorphisms (SNPs) may modify the risk of cancer. They may be
      then regarded as potential markers of carcinogenesis. The aim of this study was
      to analyze the frequency of genotypes and alleles of SNPs in DNA repair genes and
      to investigate the influence this genetic variation exerts on breast cancer in
      Polish females. The test group comprised 600 females with breast cancer and 600
      healthy controls. Genomic DNA was isolated and the SNPs in DNA repair genes were
      determined by High-Resolution Melter (HRM) technique. Following polymorphisms
      were analysed: Arg399Gln (rs25487) of the XRCC1, Gly322Asp (rs4987188) of the
      hMSH2, Lys751Gln (rs13181) of the XPD, Arg188His (rs3218536) of the XRCC2, P871L
      (rs799917) of the BRCA1 and N372H (rs144848) of the BRCA2 gene. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were calculated for each genotype and allele.
      Statistically significant correlations were identified between 4 single
      nucleotide polymorphisms and the breast cancer risk: rs25487 rs4987188 rs13181
      and rs799917. The alleles XRCC1-Gln (OR 5.11; 95% CI 5.68-11.64, p < .0001),
      hMSH2-Asp (OR 4.66; 95% CI 3.90-5.56, p < .0001), XPD-Gln (OR 2.65; 95% CI 2.24
      3.14, p < .0001) and BRCA1-L (OR 1.45; 95% CI 1.24-1.71, p < .0001) genes were
      strongly correlated with this malignancy. No correlation was found between the
      studied SNPs and tumor grading nor the lymph node status. Further research on
      larger groups is warranted to determine the influence of above-mentioned genetic
      variants on breast cancer risk.

PMID- 29209987
TI  - Genetic Investigation of Polymorphic OGG1 and MUTYH Genes Towards Increased
      Susceptibility in Lung Adenocarcinoma and its Impact on Overall Survival of Lung
      Cancer Patients Treated with Platinum Based Chemotherapy.
AB  - Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway.
      OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating
      abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired
      with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of
      bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer
      cases and 330 controls was followed by genotyping making use of PCR-RFLP.
      Logistic regression was done to analyze the risk towards lung cancer. Patients
      were followed through telephonic conversation. Kaplan meier and Cox-regression
      were used for survival analysis. OGG1 presented a high risk towards lung cancer
      (CG: OR = 2.44, p = 0.0003; CG + GG: OR = 1.88, p = 0.0093). On the same lines
      adenocarcinoma for OGG1 were potent risk factors towards lung cancer (CG: OR =
      4.72, p = 0.0002; CG + GG: OR = 3.63, p = 0.0018). Single allelic carriers for
      MUTYH gene imposed a high risk towards overall lung susceptibility and for all
      the three histology. Stratified analysis for chemotherapeutic drugs revealed
      administration of Cisplatin/Carboplatin + Pemtrexed for OGG1Ser 326 Cys showed a
      better survival (MST CG vs. CC: 9.1 vs. 0.56, p = <0.0001; HR =0.051, p =
      0.0025). Whereas, MUTYH Gln324His showed a smaller survival for mutant genotype
      (CC) (MST CC vs. GG: 4.0 vs. 9.4, p = 0.05; HR = 1.75, p = 0.26). Single allelic
      carriers for both OGG1 and MUTYH were risk factors towards lung cancer. The risk
      was amplified on combining both OGG1 and MUTYH.

PMID- 29209988
TI  - LncRNA EGOT Promotes Tumorigenesis Via Hedgehog Pathway in Gastric Cancer.
AB  - Gastric cancer (GC) is one of the mostly terminal malignancies with poor
      prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the
      breast cancer. However, the function of EGOT in GC remains unknown. This work was
      to explore the clinical value and biological significance of EGOT in GC. EGOT
      levels in GC tissue and cell were analyzed by qRT-PCR. After knockdown of EGOT,
      GC cell growth and cycle progression were detected. The expression of EGOT was
      observably elevated in GC. Upregulation of EGOT was related with lymphatic
      metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could
      significantly inhibit GC cell proliferation and arrest cycle progression in G1
      phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was
      regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog
      signaling pathway in GC cells. EGOT functions as an oncogene in GC, and may be
      useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.

PMID- 29209989
TI  - Pancreaticoduodenal artery aneurysms due to median arcuate ligament syndrome:
      what we need to know.
AB  - Median arcuate ligament (MAL) syndrome is a rare and poorly known cause of
      abdominal pain. MAL narrows the celiac artery (CA), resulting in true distal
      aneurysms, including pancreaticoduodenal artery (PDA) aneurysms. These aneurysms
      often have an aggressive course, as rupture can result in hemorrhagic shock. CT
      scan appears to be the most effective investigation for the diagnosis of PDA
      aneurysms and may reveal possible celiac artery compression. In this series, we
      describe four cases of PDA aneurysm: two ruptured aneurysms treated by an
      endovascular procedure and two non-ruptured aneurysms treated by surgery. It was
      also decided to treat CA stenosis in three of the four patients based on the
      clinical presentation (ruptured or non-ruptured) and the presence of
      peripancreatic collateral vessels on imaging. This strategy contrasts with the
      approach commonly reported in the literature, in which MAL section is mandatory
      due to the high risk of ischemia rather than the potential risk of recurrent
      aneurysm. Medical teams should be aware of this disease to improve diagnosis and
      patient management.

PMID- 29209990
TI  - Surgical anatomy of the right gastro-omental artery: a study on 100 cadaver
      dissections.
AB  - PURPOSE: The gastro-omental artery (GOA) with the greater omentum (GO) is known
      for its high quality as a vascular graft, its resistance to infections as an
      omental flap and for its multiple applications in surgery. A better knowledge of
      anatomical variations of GO and its vascularization can improve the application
      in surgery and decrease complications. The purpose of this study was to measure
      diameters and lengths of the right GOA (RGOA) and study the interindividual
      variability of these anatomical structures. METHODS: In 100 cadaveric
      dissections, we carried out dissection of the RGOA and of the GO. In 70 unfixed
      cadavers, the transillumination technique was used to identify all RGOA branches.
      In the remaining 30 cadavers, prepared with Winckler's solution, barium sulfate
      with colored latex was injected. Digital X-ray was used to measure RGOA lengths,
      internal diameters and the distribution of the omental branches. The gastro
      omental vein was also dissected. RESULTS: The mean proximal and distal diameters
      of RGOA were 2.68 (+/- 0.39) mm and 0.94 (+/- 0.24) mm, respectively. The mean
      length was 244.3 (+/- 34.4) mm. The thickness of the omentum ranged from 5 to
      15.5 mm. The arteria omentalis magna, defined in this study for the fist time as
      the longest and widest omental branch, was present in 73.3% cases. The trans
      omental arch was present in 6% cases. CONCLUSIONS: This morphometric study
      allowed us to define the vascularization and the anatomical variations of RGOA
      and GO. This may lead to improvement of applications in surgery and decrease
      complications.

PMID- 29209991
TI  - Current, Emerging, and Future Applications of Digital PCR in Non-Invasive
      Prenatal Diagnosis.
AB  - Digital PCR (dPCR) approaches have been developed for the detection of nucleic
      acids of low abundance, such as cell-free DNA, and represent an attractive and
      sensitive alternative to conventional methods, particularly in the field of non
      invasive prenatal diagnosis (NIPD). In this review, we present the principle of
      dPCR and its applications in the field of prenatal diagnosis from current and
      emerging uses, such as fetal gender determination, rhesus blood group D antigen
      genotyping, or monogenic disorders prenatal testing, to future applications, such
      as the diagnosis and monitoring of pregnancy-related disorders. We also address
      considerations for implementation of the method in a clinical laboratory and
      discuss the competiveness of dPCR over other technologies such as quantitative
      PCR or massively parallel sequencing.

PMID- 29209992
TI  - Cost Effectiveness of Karyotyping, Chromosomal Microarray Analysis, and Targeted
      Next-Generation Sequencing of Patients with Unexplained Global Developmental
      Delay or Intellectual Disability.
AB  - BACKGROUND: Genetic diagnosis of unexplained global developmental delay and
      intellectual disability (GDD/ID) often ends the diagnostic odyssey and can lead
      to changes in clinical management. OBJECTIVE: The objective of this study was to
      investigate the cost effectiveness of testing scenarios involving several methods
      used to diagnose GDD/ID: karyotyping, chromosomal microarray analysis (CMA), and
      targeted next-generation sequencing (NGS). METHODS: We used decision-tree models
      to estimate the number of genetic diagnoses, the cost from a payers' perspective
      in the USA, and the incremental cost per additional genetic diagnosis. Model
      parameters were taken from peer-reviewed literature and governmental fee
      schedules. RESULTS: CMA testing results in more genetic diagnoses at an
      incremental cost of US $2692 per additional diagnosis compared with karyotyping,
      which has an average cost per diagnosis of US $11,033. Performing both tests
      sequentially results in the same number of diagnoses, but the total cost is less
      when CMA testing is done first and karyotyping second. Furthermore, when CMA
      testing yields a variant of unknown significance, additional genetic diagnoses
      can be obtained at an incremental cost of US $4220 by CMA testing of both
      parents, and when parents are not available or the patient had a normal CMA
      result, targeted NGS of the patient can add diagnoses at a further incremental
      cost of US $12,295. CONCLUSION: These results provide a cost effectiveness
      rationale for the use of CMA as the first-tier test for the genetic diagnosis of
      unexplained GDD/ID and further indicate that testing of both parents may be cost
      effective when a variant of unknown significance is detected in the patient.

PMID- 29209993
TI  - Carrying heavy asymmetrical loads increases postural sway during quiet standing
      in older adults.
AB  - Holding asymmetrical loads in the hands is common during many daily and
      occupational activities which, depending on the load mass, may alter postural
      stability. The purpose of this study was to determine the effect of load
      magnitude held asymmetrically in the hand on postural sway in older people.
      Eighteen healthy older adults (age 65.9 +/- 5.7 years) were assessed in the
      following conditions; (1) standing without an external load (0%), (2) standing
      while holding a grocery bag containing 5%, (3) 10% and (4) 20% body mass in the
      dominant hand. The total displacement of the centre of pressure (COP) in the
      anteroposterior and mediolateral directions (cm), mean COP velocity (cm s-1) and
      COP area (cm2) were used to indirectly assess postural sway. The COP area (R 2 =
      0.96), anteroposterior (R 2 = 0.85) and mediolateral (R 2 = 0.84) COP
      displacement increased linearly with additional load. The 20% load condition
      elicited the greatest increase in postural sway (d = 2.1-3.6) compared to 0%,
      while the 5% load had no effects on sway (P >= 0.05). In contrast, the mean COP
      velocity decreased by similar amounts when holding a load at 5% (d = 1.6), 10% (d
      = 1.4) and 20% (d = 1.5) body mass, compared to 0% (all P < 0.001). The slower
      COP velocity, combined with greater COP displacements may suggest that postural
      reactions were restricted and/or delayed. From a fall-prevention perspective, it
      is advised that older people avoid holding asymmetrical external loads greater
      than 5% of body mass.

PMID- 29209994
TI  - The Role of Trypsin:Chymotrypsin in Tissue Repair.
AB  - : Tissue damage of all types, such as surgical or accidental injuries, fractures,
      and burns, stimulates a well-orchestrated, physiological process of healing,
      which ultimately leads to structural and functional restoration of the damaged
      tissues. The tissue repair process can be broadly divided into four continuous
      and overlapping phases-hemostasis and coagulation, inflammation, proliferation,
      and remodeling. If the process is interrupted or halted during any stage, it
      leads to impaired healing and formation of a chronic wound. Chronic wounds are
      associated with significant morbidity, mortality, and poor quality of life.
      Therefore, prompt and effective management of acute tissue injury is necessary to
      prevent it from progressing to a chronic wound. Proteolytic enzymes have been
      used to facilitate tissue repair since ancient times. Trypsin:chymotrypsin is an
      oral proteolytic enzyme preparation which has been in clinical use since the
      1960s. It provides better resolution of inflammatory symptoms and promotes
      speedier recovery of acute tissue injury than several of the other existing
      enzyme preparations. This review article revisits the role and clinical utility
      of trypsin:chymotrypsin combination in tissue repair. FUNDING: Torrent
      Pharmaceuticals Limited.

PMID- 29209995
TI  - Early Clinical Expressions of Insulin Resistance: The Real Enemy to Look For.
AB  - The type 2 diabetes mellitus epidemic threatens public healthcare systems
      worldwide. Efforts to prevent chronic complications of diabetes and reduce their
      associated mortality have been ineffective. Hence, early prevention of type 2
      diabetes mellitus and cardiovascular disease needs to be prioritized. This
      strategy, however, must be centered not on an approach based on hyperglycemia but
      on early pathophysiologic mechanisms, such as insulin resistance. Non-alcoholic
      fatty liver disease, androgenic alopecia, acanthosis nigricans, and polycystic
      ovarian syndrome are all well-accepted early clinical manifestations of insulin
      resistance that represent, in themselves, a risk for further development of type
      2 diabetes and that appear years before hyperglycemia. Therefore, focusing
      efforts on detecting and rigorously treating patients with early clinical
      expression of insulin resistance (insulin resistance clinical syndrome) is
      probably the course of action that needs to be taken to counterbalance the type 2
      diabetes mellitus epidemic.

PMID- 29209996
TI  - Understanding ownership of patient care: A dual-site qualitative study of faculty
      and residents from medicine and psychiatry.
AB  - INTRODUCTION: With changes in duty hours and supervision requirements, educators
      have raised concerns about erosion of patient care ownership by resident
      physicians. However, the definition of ownership is unclear. This qualitative
      study investigated definitions of ownership in medicine and psychiatry faculty
      and residents. METHODS: The authors distributed an anonymous online survey
      regarding definitions of ownership to faculty and residents at the psychiatry and
      internal medicine residency programs at the University of Washington and the
      Harvard Longwood psychiatry residency and conducted a qualitative analysis of
      free-text responses to identify emergent themes. RESULTS: 225 faculty (48.6%) and
      131 residents (43.8%) across the three programs responded. Responses yielded
      themes in five domains: Physician Actions, Physician Attitudes, Physician
      Identity, Physician Qualities, and Quality of Patient Care. All groups identified
      themes of advocacy, communication and care coordination, decision-making, follow
      through, knowledge, leadership, attitudes of going 'above and beyond' and 'the
      buck stops here', responsibility, serving as primary provider, demonstrating
      initiative, and providing the best care as central to ownership. Residents and
      faculty had differing perspectives on 'shift work' and transitions of care and on
      resident decision-making as elements of ownership. DISCUSSION: This study
      expanded and enriched the definition of patient care ownership. There were more
      similarities than differences across groups, a reassuring finding for those
      concerned about a decreasing understanding of ownership in trainees. Findings
      regarding shared values, shift work, and the decision-making role can inform
      educators in setting clear expectations and fostering ownership despite changing
      educational and care models.

PMID- 29209997
TI  - [18F]-BMS-747158-02PET imaging for evaluating hepatic mitochondrial complex
      1dysfunction in a mouse model of non-alcoholic fatty liver disease.
AB  - BACKGROUND: Mitochondrial dysfunction is one of the main causes of non-alcohol
      fatty liver disease (NAFLD). [18F]-BMS-747158-02 (18F-BMS) which was originally
      developed as a myocardial perfusion imaging agent was reported to bind
      mitochondrial complex-1 (MC-1). The aim of this study was to investigate the
      potential use of 18F-BMS for evaluating hepatic MC-1 activity in mice fed a
      methionine- and choline-deficient (MCD) diet. Male C57BL/6J mice were fed a MCD
      diet for up to 2 weeks. PET scans with 18F-BMS were performed after 1 and 2 weeks
      of the MCD diet. 18F-BMS was intravenously injected into mice, and the uptake
      (standardized uptake value (SUV)) in the liver was determined. The binding
      specificity for MC-1 was assessed by pre-administration of rotenone, a specific
      MC-1 inhibitor. Hepatic MC-1 activity was measured using liver homogenates
      generated after each positron emission tomography (PET) scan. Blood biochemistry
      and histopathology were also assessed. RESULTS: In control mice, hepatic 18F-BMS
      uptake was significantly inhibited by the pre-injection of rotenone. The uptake
      of 18F-BMS was significantly decreased after 2 weeks of the MCD diet. The SUV at
      30-60 min was well correlated with hepatic MC-1 activity (r = 0.73, p < 0.05).
      Increases in plasma ALT and AST levels were also noted at 1 and 2 weeks. Mild
      hepatic steatosis with or without minimal inflammation was histopathologically
      observed at 1 and 2 weeks in mice liver on the MCD diet. However, inflammation
      was observed only at 2 weeks in mice on the MCD diet. CONCLUSIONS: The present
      study demonstrated that 18F-BMS is a potential PET probe for quantitative imaging
      of hepatic MC-1 activity and its mitochondrial dysfunction induced by steatosis
      and inflammation, such as in NAFLD.

PMID- 29209998
TI  - Rodent ultrasonic vocalizations as biomarkers of future alcohol use: A predictive
      analytic approach.
AB  - Excessive alcohol consumption has a vast, negative impact on society. Rodent
      models have been successful in furthering our understanding of the biological
      underpinnings that drive alcohol consumption. Rodents emit ultrasonic
      vocalizations (USVs) that are each composed of several acoustic characteristics
      (e.g., frequency, duration, bandwidth, power). USVs reflect neurotransmitter
      activity in the ascending limb of the mesolimbic dopaminergic and cholinergic
      neurotransmitter systems and serve as noninvasive, real-time biomarkers of
      dopaminergic and cholinergic neurotransmission in the limbic system. In the
      present study, we recorded spontaneously emitted USVs from alcohol-naive Long
      Evans (LE) rats and then measured their alcohol intake. We compared the USV
      acoustic characteristics and alcohol consumption data from these LE rats with
      previously published data from selectively bred high-alcohol (P and HAD-1) and
      low-alcohol (NP and LAD-1) drinking lines from studies with the same experimental
      method. Predictive analytic techniques were applied simultaneously to this
      combined data set and revealed that (a) USVs emitted by alcohol-naive rats
      accurately discriminated among high-alcohol consuming, LE, and low-alcohol
      consuming rat lines, and (b) future alcohol consumption in these same rat lines
      was reliably predicted from the USV data collected in an alcohol-naive state. To
      our knowledge, this is the first study to show that alcohol consumption is
      predicted directly from USV profiles of alcohol-naive rats. Because USV acoustic
      characteristics are sensitive to underlying neural activity, these findings
      suggest that baseline differences in mesolimbic cholinergic and dopaminergic tone
      could determine the propensity for future alcohol consumption in rodents.

PMID- 29209999
TI  - Elaborative feedback: Engaging reward and task-relevant brain regions promotes
      learning in pseudoword reading aloud.
AB  - Although much is known about the cognitive and neural basis of establishing
      letter-sound mappings in learning word forms, relatively little is known about
      what makes for the most effective feedback during this process. We sought to
      determine the neural basis by which elaborative feedback (EF), which contains
      both reward-related and content-specific information, may be more helpful than
      feedback containing only one kind of information (simple positive feedback, PF)
      or the other (content feedback, CF) in learning orthography-phonology (spelling
      sound) mappings for novel letter strings. Compared to CF, EF activated the
      ventromedial prefrontal cortex, implicated in reward processing. Compared to PF,
      EF activated the posterior middle temporal, superior temporal, and supramarginal
      gyri-regions implicated in orthography-phonology conversion. In the same
      comparison, EF also activated the left fusiform gyrus/visual word form area
      implicated in orthographic processing. Also EF, but not CF or PF, modulated
      activity in the caudate nucleus. In a postscan questionnaire, EF and PF were
      rated as more pleasant than CF, suggesting that modulation of the caudate for EF
      may be due to the coupling of reward and skill content. These findings suggest
      the enhanced effectiveness of EF may be due to concurrent activation of reward
      related and task-relevant brain regions.

PMID- 29210000
TI  - Sleep quality is associated with the severity of clinical symptoms in Parkinson's
      disease.
AB  - Sleep disorders are very common in Parkinson's disease (PD), being associated
      with several other conditions, mainly psychiatric disorders. The present study
      was designed to assess sleep quality in Brazilian patients with PD and to
      evaluate whether sleep changes are associated with clinical variables, especially
      neuropsychiatric symptoms in PD. Patients diagnosed with PD were subjected to a
      comprehensive clinical evaluation that included the assessment of motor,
      cognitive and psychiatric symptoms. Our study showed that sleep complaints are
      frequent in PD and worse sleep quality is associated with depressive and anxious
      symptoms, poorer cognitive performance and greater severity of PD symptoms. In
      the multivariate analysis, older age, greater severity of anxiety and PD remained
      as significant predictors of worse sleep quality. In conclusion, sleep
      complaints, depressive and anxiety symptoms are frequent in PD patients. Older
      age, disease severity and anxiety symptoms are significant predictors of poorer
      sleep quality in PD patients.

PMID- 29210001
TI  - High-intensity exercise interventions in cancer survivors: a systematic review
      exploring the impact on health outcomes.
AB  - PURPOSE: There is an increasing body of evidence underpinning high-intensity
      exercise as an effective and time-efficient intervention for improving health in
      cancer survivors. The aim of this study was to, (1) evaluate the efficacy and (2)
      the safety of high-intensity exercise interventions in improving selected health
      outcomes in cancer survivors. METHODS: Design Systematic review. Data sources
      Google Scholar and EBSCO, CINAHL Plus, Computers and Applied Sciences Complete,
      Health Source-Consumer Edition, Health Source: Nursing/Academic Edition, MEDLINE,
      Web of Science and SPORTDiscuss from inception up until August 2017. Eligibility
      criteria Randomized controlled trials of high-intensity exercise interventions in
      cancer survivors (all cancer types) with health-related outcome measures. The
      guidelines adopted for this review were the Preferred Reporting Items for
      Systematic Reviews and Meta-Analysis (PRISMA). RESULTS: The search returned 447
      articles, of which nine articles (n = 531 participants mean, age 58 +/- 9.5
      years) met the eligibility criteria. Exercise interventions of between 4 and 18
      weeks consisting of high-intensity interval bouts of up to 4-min were compared
      with a continuous moderate intensity (CMIT) intervention or a control group. High
      intensity exercise interventions elicited significant improvements in VO2 max,
      strength, body mass, body fat and hip and waist circumference compared with CMIT
      and/or control groups. The studies reviewed showed low risk in participating in
      supervised high-intensity exercise interventions. Mixed mode high-intensity
      interventions which included both aerobic and resistance exercises were most
      effective improving the aerobic fitness levels of cancer survivors by 12.45
      21.35%, from baseline to post-intervention. CONCLUSION: High-intensity exercise
      interventions improved physical and physiological health-related outcome measures
      such as cardiovascular fitness and strength in cancer survivors. Given that high
      intensity exercise sessions require a shorter time commitment, it may be a useful
      modality to improve health outcomes in those who are time poor. The risk of
      adverse events associated with high-intensity exercise was low.

PMID- 29210002
TI  - Tolerance of the eriophyid mite Aceria salsolae to UV-A light and implications
      for biological control of Russian thistle.
AB  - Aceria salsolae (Acari: Eriophyidae) is being evaluated as a candidate biological
      control agent of Russian thistle (Salsola tragus, Chenopodiaceae), a major
      invasive weed of rangelands and dryland crops in the western USA. Prior
      laboratory host range testing under artificial lighting indicated reproduction on
      non-native Bassia hyssopifolia and on a native plant, Suaeda calceoliformis.
      However, in field tests in the native range, mite populations released on these
      'nontarget' plants remained low. We hypothesized that UV-A light, which can
      affect behavior of tetranychid mites, would affect populations of the eriophyid
      A. salsolae differently on the target and nontarget plant species, decreasing the
      mite's realized host range. Plants were infested with A. salsolae under lamps
      that emitted UV-A, along with broad-spectrum lighting, and the size of mite
      populations and plant growth was compared to infested plants exposed only to
      broad-spectrum light. Russian thistle supported 3- to 55-fold larger mite
      populations than nontarget plants regardless of UV-A treatment. UV-A exposure did
      not affect mite populations on Russian thistle or S. calceoliformis, whereas it
      increased populations 7-fold on B. hyssopifolia. Main stems on nontarget plants
      grew 2- to 6-fold faster than did Russian thistle under either light treatment.
      The two nontarget plants attained greater volume under the control light regime
      than UV-A, but Russian thistle was unaffected. Although Russian thistle was
      always the superior host, addition of UV-A light to the artificial lighting
      regime did not reduce the ability of A. salsolae to reproduce on the two
      nontarget species, suggesting that UV-B or other environmental factors may be
      more important in limiting mite populations in the field.

PMID- 29210003
TI  - Abscisic Acid Insensitive 4 transcription factor is an important player in the
      response of Arabidopsis thaliana to two-spotted spider mite (Tetranychus urticae)
      feeding.
AB  - Plants growing in constantly changeable environmental conditions are compelled to
      evolve regulatory mechanisms to cope with biotic and abiotic stresses. Effective
      defence to invaders is largely connected with phytohormone regulation, resulting
      in the production of numerous defensive proteins and specialized metabolites. In
      our work, we elucidated the role of the Abscisic Acid Insensitive 4 (ABI4)
      transcription factor in the plant response to the two-spotted spider mite (TSSM).
      This polyphagous mite is one of the most destructive herbivores, which sucks
      mesophyll cells of numerous crop and wild plants. Compared to the wild-type (Col
      0) Arabidopsis thaliana plants, the abi4 mutant demonstrated increased
      susceptibility to TSSM, reflected as enhanced female fecundity and greater
      frequency of mite leaf damage after trypan blue staining. Because ABI4 is
      regarded as an important player in the plastid-to-nucleus retrograde signalling
      process, we investigated the plastid envelope membrane dynamics using stroma
      associated fluorescent marker. Our results indicated a clear increase in the
      number of stroma-filled tubular structures deriving from the plastid membrane
      (stromules) in the close proximity of the site of mite leaf damage, highlighting
      the importance of chloroplast-derived signals in the response to TSSM feeding
      activity.

PMID- 29210004
TI  - A mathematical model of recurrent spreading depolarizations.
AB  - A detailed biophysical model for a neuron/astrocyte network is developed in order
      to explore mechanisms responsible for the initiation and propagation of recurrent
      cortical spreading depolarizations. The model incorporates biophysical processes
      not considered in the earlier models. This includes a model for the Na+-glutamate
      transporter, which allows for a detailed description of reverse glutamate uptake.
      In particular, we consider the specific roles of elevated extracellular glutamate
      and K+ in the initiation, propagation and recurrence of spreading
      depolarizations.

PMID- 29210005
TI  - The novel role of IL-37 in prostate cancer: evidence as a promising
      radiosensitizer.
AB  - Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the USA.
      Radiation therapy (RT) is widely considered the standard treatment for PCa. IL-37
      is an IL-1 family member, and it has been extensively studied in immunity.
      However, no studies have been done regarding its potential as a radiosensitizer.
      This study is designed to investigate the direct effect of IL-37 on growth of
      DU145 and PC-3, two widely studied PCa cell lines, and to investigate whether IL
      37 could be used as a radiosensitizer for PCa. Clonogenic survival and quick cell
      proliferation assays along with immunohistochemistry, TUNEL staining, and caspace
      3 activity assay kits as well as RT-PCR were used in this study. Our results
      showed that IL-37 has little direct effect on growth of PCa. However, IL-37/RT
      enhanced RT-induced inhibition of cell proliferation and apoptosis in both cell
      lines. We further found that IL-37/RT upregulated the mRNA expression of p27,
      Fas, and Bax, while downregulating the mRNA expression of cdk2 in DU145 cells.
      These findings suggest that IL-37 has the potential to be used as a
      radiosensitizer for PCa and warrants further investigation.

PMID- 29210006
TI  - Triiodothyronine differentially modulates the LH and FSH synthesis and secretion
      in male rats.
AB  - Hypothyroidism and thyrotoxicosis produce adverse effects in male reproduction by
      unknown mechanisms. We investigated whether triiodothyronine (T3) modulates
      luteinizing hormone (LH) and follicle stimulating hormone (FSH)
      synthesis/secretion, by inducing different thyroid states. In hypothyroidism, the
      content of Lhb and Fshb mRNAs was increased, while their association to ribosomes
      and the protein content were reduced and the serum LH and FSH concentrations were
      augmented and decreased, respectively. Thyrotoxicosis reduced Lhb mRNA and LH
      serum concentration, and increased Lhb mRNA translational rate. The Fshb mRNA
      content and its association to ribosomes were also increased, whereas FSH serum
      concentrations were comparable to euthyroid levels. Acute T3 treatment decreased
      the total content of Lhb and Fshb mRNAs, and increased their association to
      ribosomes, as well as the LHB and FSHB contents in secretory granules. This study
      shows that T3 acts on gonadotrophs, resulting in direct effects on LH and FSH
      synthesis/secretion of male rats, suggesting that some reproductive disorders
      observed in men may be associated with thyroid hormone imbalances.

PMID- 29210007
TI  - Bilateral is superior to unilateral varicocelectomy in infertile males with left
      clinical and right subclinical varicocele: a prospective randomized controlled
      study.
AB  - PURPOSE: The purpose of this study is to compare the effect of bilateral versus
      unilateral varicocelectomy on seminal response and spontaneous pregnancy rates in
      infertile male patients with left clinical and right subclinical varicocele.
      METHODS: A total of 358 infertile men with left clinical and right subclinical
      varicocele were randomized to group that underwent bilateral (n = 179) and group
      that underwent unilateral microsurgical subinguinal varicocelectomy (n = 179).
      Baseline data regarding male age, female partner age, grade of varicocele body
      mass index, bilateral testicular volume and serum follicle-stimulating hormone,
      luteinizing hormone, total testosterone levels and infertility duration and semen
      parameters were gathered. One year after the surgery, semen parameters including
      sperm volume, sperm concentration, normal sperm morphology, progressive motility
      and sperm DNA fragmentation index were recorded and any pregnancy was also
      documented via telephone calls and hospital visits. RESULTS: We found the
      baseline characteristics were comparable between the two groups. The seminal
      parameters had significant improvements 1 year postoperatively in both groups.
      However, the bilateral group showed significantly greater improvements than the
      unilateral group in sperm concentration, normal sperm morphology and progressive
      motility. Besides, the pregnancy rate was statistically higher in the bilateral
      group after the surgery (42.5 versus 26.0%, bilateral versus unilateral group).
      CONCLUSION: In conclusion, our study indicated that bilateral is superior to
      unilateral varicocelectomy in infertile males with left clinical and right
      subclinical varicocele, which is associated with greater improvements in sperm
      concentration, normal sperm morphology and progressive motility and spontaneous
      pregnancy rate after the surgery.

PMID- 29210008
TI  - Development and surgical removal of an epiretinal membrane in infantile nystagmus
      syndrome: a new type of oscillopsia.
AB  - PURPOSE: To report and discuss a focal oscillopsia in a small area of the visual
      field produced by, and after the removal of, an epiretinal membrane (ERM) in an
      individual with infantile nystagmus syndrome (INS) since birth with no associated
      afferent visual deficits. STUDY DESIGN: A retrospective case report. METHODS: A
      chart review, including clinical and electrophysiological data. A 74 y/o man with
      INS and an epiretinal membrane was studied. Detailed studies of the retina post
      removal of an epiretinal membrane, with consequent changes in best-corrected
      visual acuity (BCVA), and subjective oscillopsia compared to INS waveforms. OCT
      measurements and eye-movement data from digital video and scleral search-coil
      systems were used. RESULTS: The monocular ERM produced an unexpected focal area
      of torsional/vertical oscillopsia (noted 1 year prior to the ERM surgery) in the
      portion of the visual field that corresponded with distortions from the ERM. The
      remainder of the visual field, corresponding with normal healthy retina was
      unaffected and stable in all planes. Post-removal, BCVA improved with
      redevelopment of the foveal pit and focal oscillopsia became less noticeable but
      remained due to the retinal distortion. CONCLUSIONS: In patients with INS,
      complete oscillopsia suppression across the visual field requires undistorted
      vision. If a retinal area of visual distortion develops or results from retinal
      surgery, a symptomatic island of oscillopsia in one or more planes may result.

PMID- 29210009
TI  - Influence of comorbidities on the implementation of the fundus examination in
      patients with newly diagnosed type 2 diabetes.
AB  - AIMS: To investigate the influence of comorbidities on undergoing a diabetic eye
      examination in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
      DESIGN: Retrospective cohort study METHODS: This was a retrospective cohort study
      using data from health insurance claims made between January 2005 and March 2013
      in Japan. The primary outcome was implementation of the fundus examination that
      includes fundus photography, ophthalmoscopy and optical coherence tomography by a
      doctor within one year of initial drug therapy for Type2 Diabetes Mellitus
      (T2DM). We used multivariable logistic regression models with adjustment for
      demographic parameters to investigate the influence of comorbidities
      (hypertension and/or hyperlipidemia) on patients with T2DM receiving fundus
      examinations. We conducted an additional analysis to investigate whether the site
      of treatment might influence the performance of fundus examinations in patients
      with T2DM. RESULTS: A total of 6,492 patients were eligible for this analysis, of
      which 1,044 (16.1%) had comorbidities and 2,212 (34.1%) received the fundus
      examination. In the multivariable analysis, there was a significant association
      between comorbidities and a lower proportion of examination implementation (odds
      ratio [OR], 0.57; 95% confidence interval [CI], 0.48-0.68; P<0.001). The
      implementation proportion for patients treated for comorbidities and T2DM in the
      same facility was also low (OR, 0.52; 95% CI, 0.43-0.63; P<0.001). CONCLUSIONS:
      These results suggest that the proportion of taking fundus examination is low
      among patients with comorbidities, especially in patients treated at the same
      facility for comorbidities and T2DM. This may help to increase the proportion of
      T2DM patients receiving fundus examinations.

PMID- 29210011
TI  - N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older
      Patients with Chronic Pain.
AB  - BACKGROUND: Ultra-micronized palmitoylethanolamide (um-PEA) represents an
      attractive option for chronic pain control in complex older patients at higher
      risk of adverse effects with traditional analgesics. OBJECTIVE: The aim of this
      study was to determine the effectiveness of um-PEA versus placebo on chronic pain
      intensity and function in individual geriatric patients. DESIGN: We performed
      randomized, blinded N-of-1 trials with two 3-week um-PEA versus placebo
      comparisons, separated by 2-week washout periods. PARTICIPANTS: The study
      included outpatients aged >= 65 years with chronic, non-cancer, non-ischemic pain
      in the back, joints, or limbs. INTERVENTION: Patients were randomized to Um-PEA
      600 mg or placebo twice daily. MEASUREMENTS: Pain intensity was measured using an
      11-point visual numeric scale. Functional impairment was measured using a Back
      Pain Functional Scale. Impact of each N-of-1 trial was measured on the
      clinician's intention to treat and confidence. RESULTS: Ten of 11 eligible
      patients consented over 7 months [all female, mean age 83.2 years (SD 4.6)].
      Three patients interrupted the trial: one had diarrhea (under placebo), one for
      low adherence, and one for intercurrent pneumonia. A small statistically
      significant effect in favor of um-PEA was seen at the mixed method analyses in
      two patients (effect size equal to 8% of the baseline pain). A statistically
      significant impact on function was found in one patient. After the trial, um-PEA
      was prescribed to four patients; in two patients the clinician changed their pre
      trial intention to treat; the clinician confidence in the treatment plan either
      increased (5) or remained the same (2). CONCLUSIONS: Our experience confirmed
      that N-of-1 trials may help make personalized evidence-based decisions in complex
      older patients, with special feasibility considerations. CLINICALTRIALS.GOV:
      NCT02699281.

PMID- 29210013
TI  - Transactions of the Linnean.

PMID- 29210012
TI  - The invisibility of fisheries in the process of hydropower development across the
      Amazon.
AB  - We analyze the invisibility of fisheries and inadequacy of fishers' participation
      in the process of hydropower development in the Amazon, focusing on gaps between
      legally mandated and actual outcomes. Using Ostrom's institutional design
      principles for assessing common-pool resource management, we selected five case
      studies from Brazilian Amazonian watersheds to conduct an exploratory comparative
      case-study analysis. We identify similar problems across basins, including
      deficiencies in the dam licensing process; critical data gaps; inadequate
      stakeholder participation; violation of human rights; neglect of fishers'
      knowledge; lack of organization and representation by fishers' groups; and lack
      of governmental structure and capacity to manage dam construction activities or
      support fishers after dam construction. Fishers have generally been marginalized
      or excluded from decision-making regarding planning, construction, mitigation,
      compensation, and monitoring of the social-ecological impacts of hydroelectric
      dams. Addressing these deficiencies will require concerted investments and
      efforts by dam developers, government agencies and civil society, and the
      promotion of inter-sectorial dialogue and cross-scale participatory planning and
      decision-making that includes fishers and their associations.

PMID- 29210010
TI  - Management of diabetic macular edema in Japan: a review and expert opinion.
AB  - Diabetic retinopathy is a frequent cause of visual impairment in working-age
      adults (>= 30 years) and in Japan is most commonly observed in those aged 50-69
      years. Diabetic macular edema (DME) is one of the main causes of vision
      disturbance in diabetic retinopathy, which is a clinically significant
      microvascular complication of diabetes. Anti-vascular endothelial growth factor
      (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve
      sustained long-term improvement in visual acuity, conventional laser
      photocoagulation, vitrectomy and steroid therapy are also expected to play a role
      in the treatment of DME. This review summarizes the epidemiology and pathology of
      diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and
      treatment of DME, and underscores the importance of systemic management of the
      disease in the context of the current health care situation in Japan. Finally,
      the unmet needs of patients with DME and prospects for research are discussed.
      The weight of evidence suggests that it is important to establish a multipronged
      treatment strategy centered on anti-VEGF therapy.

PMID- 29210014
TI  - Scoping review of response shift methods: current reporting practices and
      recommendations.
AB  - BACKGROUND: Response shift (RS) has been defined as a change in the meaning of an
      individual's self-evaluation of his/her health status and quality of life.
      Several statistical model- and design-based methods have been developed to test
      for RS in longitudinal data. We reviewed the uptake of these methods in patient
      reported outcomes (PRO) literature. METHODS: CINHAHL, EMBASE, Medline, ProQuest,
      PsycINFO, and Web of Science were searched to identify English-language articles
      about RS published until 2016. Data on year and country of publication, PRO
      measure adopted, RS detection method, type of RS detected, and testing of
      underlying model assumptions were extracted from the included articles. RESULTS:
      Of the 1032 articles identified, 101 (9.8%) articles were included in the study.
      While 54.5 of the articles reported on the Then-test, 30.7% of the articles
      reported on Oort's or Schmitt's structural equation modeling (SEM) procedure.
      Newer RS detection methods, such as relative importance analysis and random
      forest regression, have been used less frequently. Less than 25% reported on
      testing the assumptions underlying the adopted RS detection method(s).
      CONCLUSIONS: Despite rapid methodological advancements in RS research, this
      review highlights the need for further research about RS detection methods for
      complex longitudinal data and standardized reporting guidelines.

PMID- 29210015
TI  - Internet use, social networks, loneliness, and quality of life among adults aged
      50 and older: mediating and moderating effects.
AB  - BACKGROUND: The increase in longevity of people on one hand, and on the other
      hand the fact that the social networks in later life become increasingly
      narrower, highlights the importance of Internet use to enhance quality of life
      (QoL). However, whether Internet use increases or decreases social networks,
      loneliness, and quality of life is not clear-cut. PURPOSES: To explore the direct
      and/or indirect effects of Internet use on QoL, and to examine whether ethnicity
      and time the elderly spent with family moderate the mediation effect of Internet
      use on quality of life throughout loneliness. METHODS: This descriptive
      correlational study was carried out in 2016 by structured interviews with a
      convenience sample of 502 respondents aged 50 and older, living in northern
      Israel. Bootstrapping with resampling strategies was used for testing mediation a
      model. RESULTS: Use of the Internet was found to be positively associated with
      QoL. However, this relationship was mediated by loneliness, and moderated by the
      time the elderly spent with family members. In addition, respondents' ethnicity
      significantly moderated the mediation effect between Internet use and loneliness.
      CONCLUSIONS: Internet use can enhance QoL of older adults directly or indirectly
      by reducing loneliness. However, these effects are conditional on other
      variables. The indirect effect moderated by ethnicity, and the direct effect
      moderated by the time the elderly spend with their families. Researchers and
      practitioners should be aware of these interactions which can impact loneliness
      and quality of life of older persons differently.

PMID- 29210016
TI  - Amphibiophilus mooiensis n. sp. (Nematoda: Amphibiophilidae), a parasite of
      Amietia delalandii (Dumeril & Bibron) (Amphibia: Pyxicephalidae) from South
      Africa.
AB  - Four species of the genus Amphibiophilus Skrjabin, 1916 from pyxycephalid frogs
      in southern and central Africa are currently recognised as valid. Several
      specimens of Amphibiophilus were found in material from the common river frog,
      Amietia delalandii (Dumeril & Bibron) (Amphibia: Pyxicephalidae), collected in
      Potchefstroom (North-West Province, South Africa). These specimens clearly differ
      from all previously known species by the shape of the distal end of the spicule,
      the shape of the gubernaculum and the structure of the synlophe. They are, thus,
      considered as a new species, Amphibiophilus mooiensis. As all other species in
      the family Amphibiophilidae Durette-Desset & Chabaud, 1981, A. mooiensis n. sp.
      possesses a number of archaic characters, such as a buccal capsule with a well
      developed dorsal oesophageal tooth, six inner labial papillae, six outer labial
      papillae and four cephalic papillae. Molecular data (cox1 and ITS-28S rDNA
      sequences) are provided and host and geographical specificity are discussed.

PMID- 29210017
TI  - Vampirolepis kulkinae n. sp. (Cyclophyllidea: Hymenolepididae) from the common
      noctule bat Nyctalus noctula (Schreber) (Chiroptera: Vespertilionidae) in
      Kazakhstan.
AB  - A previously unrecognised species of hymenolepidid cestode attributable to
      Vampirolepis Spassky, 1954 is described based on specimens from the common
      noctule bat Nyctalus noctula (Schreber) (Chiroptera: Vespertilionidae) from
      southeastern Kazakhstan (Dzungarian Alatau). Specimens of Vampirolepis kulkinae
      n. sp. differ from the morphologically similar congeners based on the number,
      size and shape of the rostellar hooks. The new species is further distinguished
      from additional cestodes attributed to Vampirolepis (sensu lato) by the
      arrangement of the testes in one row, egg structure (i.e. thin outer coat and
      emryophore without polar filaments) and the relative position and length of the
      cirrus-sac. This is the first species of the genus Vampirolepis described from
      Kazakhstan.

PMID- 29210018
TI  - Descriptions of two new species of feather mites (Acarina: Psoroptidia:
      Pteronyssidae) from Ivory Coast.
AB  - Two new feather mite species of the family Pteronyssidae Oudemans, 1941 collected
      from birds captured in Ivory Coast are described: Pteronyssoides cyanomitrae n.
      sp. from Cyanomitra obscura (Jardine) (Passeriformes: Nectariniidae) and
      Conomerus pygmaeus n. sp. from Hylia prasina (Cassin) (Passeriformes:
      Macrosphenidae). Pteronyssoides cyanomitrae n. sp. belongs to the nectariniae
      species group and differs from the closest species, P. garioui Gaud & Mouchet,
      1959, in having, in males, the adanal shield present and setae f longer than
      setae d on the tarsus III; females of this species have the hysteronotal shield
      with two small median incisions on the anterior margin barely extending beyond
      the level of setae e2. Conomerus pygmaeus n. sp. is the first species of this
      genus found on a passerine host, and seems to be more similar to C. sclerosternus
      Gaud, 1990. This new species has the following distinctive characters: in
      females, the opisthosoma has small lobe-like extensions and the central sclerite
      is fused posteriorly with the lateral opisthosomal sclerites; in males, coxal
      fields I-IV lack large sclerotised areas.

PMID- 29210019
TI  - Pathology of stent implantation in internal mammary artery.
AB  - The internal mammary artery (IMA) is the most durable conduit for bypassing the
      left anterior descending (LAD) coronary artery in patients undergoing coronary
      artery bypass graft surgery (CABG). However, little is known about how the IMA
      reacts histologically to stent implantation. From CVPath stent registry (1048
      lesions, 614 cases), we obtained 4 stent lesions (2 bare metal stents, 2 drug
      eluting stents) involving IMA grafts. The mean age of our patients was 63 years
      and the duration of stent implantation in the IMA ranged from 5 days to 5 years.
      Stented arteries were dissected from hearts and embedded in plastic, segmented at
      3 mm intervals, sectioned at 4-6 microns and stained with H&E and Movat
      pentachrome stains. Histological observations were performed. Majority of stents
      (3 of 4) were implanted in anastomosis between IMA and LAD while 1 stent was
      implanted in IMA body. One stent with duration of 5 days showed stent thrombosis
      while others were all patent with fully coverage by varying degrees of neointima.
      Foamy macrophage, lipid pool and calcification in neointima were observed in 1
      stent with duration of 5 years but it was limited only to the distal LAD part
      within the stented segment. Overall, in this small pathologic series, the
      majorities of stents were implanted in IMA-to-LAD anastomosis site and
      demonstrated acceptable pathologic responses.

PMID- 29210020
TI  - Effects of visual and cognitive interference on joint contributions in perturbed
      standing: a temporal and spectral analysis.
AB  - Postural balance requires using joint strategies which may be changed from normal
      conditions by interfering with the sensory information. The goal of the present
      study was to quantitatively evaluate the role of the joint mechanisms during
      perturbed stance. Visual and cognitive interference was imposed to sixteen
      healthy young males under rotational toes-down or up perturbations. Power
      spectral analysis was employed to distinguish the joint contribution and their in
      or out-phase co-works. Results showed that addition of cognitive loads reduce
      the stability by increasing the center of mass (CoM) power to three times
      greater. Besides the CoM, the knee and hip powers were also significantly
      enhanced by the cognitive loads (p < .004), but the ankle was not influenced by
      cognition involvement (p > .05). Elimination of the vision had lower effect on
      the time and spectral functions of the knee and hip while the ankle rotations
      were increased due to the lack of visual feedback (p = .001). The toes-down
      perturbations resulted in more prominent contribution of the knee while the toes
      up evoked the hip joint to keep the balance more than the other joints. Addition
      of the cognitive loads hindered the reactions of the joint mechanisms and vision
      caused more conservative responses of the joints.

PMID- 29210021
TI  - Design and Operation of the Transformed National Healthy Start Evaluation.
AB  - Purpose Improving pregnancy outcomes for women and children is one of the
      nation's top priorities. The Healthy Start (HS) program was created to address
      factors that contribute to high infant mortality rates (IMRs) and persistent
      disparities in IMRs. The program began in 1991 and was transformed in 2014 to
      apply lessons from emerging research, past evaluation findings, and expert
      recommendations. To understand the implementation and impact of the transformed
      program, there is a need for a robust and comprehensive evaluation. Description
      The national HS evaluation will include an implementation evaluation, which will
      describe program components that affect outcomes; a utilization evaluation, which
      will examine the characteristics of women and infants who did and did not utilize
      the program; and an outcome evaluation, which will assess the program's
      effectiveness with regard to producing expected outcomes among the target
      population. Data sources include the National HS Program Survey, a HS participant
      survey, and individual-level program data linked to vital records and the
      Pregnancy Risk Assessment Monitoring System (PRAMS) survey. Assessment
      Descriptive analyses will be used to examine differences in risk profiles between
      participants and non-participants, as well as to calculate penetration rates for
      high-risk women in respective service areas. Multivariable analyses will be used
      to determine the impact of the program on key outcomes and will explore variation
      by dose, type of services received, and grantee characteristics. Conclusion
      Evaluation findings are expected to inform program decisions and direction,
      including identification of effective program components that can be spread and
      scaled.

PMID- 29210027
TI  - Erratum to: PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia
      (CLL).

PMID- 29210022
TI  - Trochleoplasty procedures show complication rates similar to other patellar
      stabilizing procedures.
AB  - PURPOSE: Trochleoplasty aims to restore patellar stability. Various techniques
      have been described and almost all authors report successful results. However,
      the procedure has a significant risk of complications. Purpose of this study was
      to perform a systematic review and meta-analysis of the available literature to
      assess the rate of complications after the various techniques used for
      trochleoplasty procedures. MATERIALS AND METHODS: MEDLINE, EMBASE, Web of Science
      and Cochrane Library databases were searched. Studies on patients with recurrent
      patellar instability treated with a trochleoplasty with or without additional
      procedure, and reported complications were included. The primary outcome was the
      rate of complications per technique. A meta-analysis was performed whenever three
      or more studies per surgical technique could be included. RESULTS: The selection
      process resulted in 20 studies included for analysis. A lateral facet elevating
      trochlear osteotomy was reported by two studies, ten studies reported on a
      Bereiter trochleoplasty, five on a Dejour trochleoplasty, one on an arthroscopic
      technique, one on a 'modified' technique and one on a recession wedge
      trochleoplasty. Meta-analysis showed that proportion of recurrent dislocation was
      0.04 (95% CI 0.02-0.07) for Bereiter trochleoplasty and 0.02 (95% CI 0-0.08) for
      Dejour trochleoplasty. These proportions were 0.06 (95% CI 0.02-0.13) and 0.09
      (95% CI 0.03-0.27) for recurrent instability, 0.07 (95% CI 0.02-0.19) and 0.12
      (95% CI 0.00-0.91) for patellofemoral osteoarthritis and 0.08 (95% CI 0.04-0.14)
      and 0.20 (95% CI 0.11-0.32) for further surgery respectively. CONCLUSION: This
      study demonstrates that the complications after a Bereiter and Dejour
      trochleoplasty including additional procedures are in the range of those of other
      patellar stabilizing procedures. For four other techniques, no meta-analysis
      could be performed. The clinical relevance of this study is that it provides
      clinicians with the best currently available evidence on the rate of
      complications after trochleoplasty procedures. This can be helpful in the process
      of deciding whether or not to perform such a procedure, and can be used to better
      inform patients about the advantages and disadvantages of different
      trochleoplasty procedures. LEVEL OF EVIDENCE: Level IV.

PMID- 29210028
TI  - Antimicrobial peptides sourced from post-butter processing waste yak milk protein
      hydrolysates.
AB  - Yak butter is one of the most important foods for the Tibetan people. Of note,
      its production yields waste yak milk as a by-product. In this work, waste yak
      milk protein hydrolysates made via Pepsin hydrolysis were shown to have
      antimicrobial activity. Furthermore, an innovative method of magnetic liposome
      adsorption combined with reversed-phase high performance liquid chromatography
      (RP-HPLC) was developed to screen for and purify the antimicrobial peptides. Two
      antimicrobial peptides were obtained and their amino acid sequences were
      determined by N-sequencing, namely Arg-Val-Met-Phe-Lys-Trp-Ala and Lys-Val-Ile
      Ser-Met-Ile. The antimicrobial activity spectra of Arg-Val-Met-Phe-Lys-Trp-Ala
      included Bacillus subtilis, Staphylcoccus aureus, Listeria innocua, Escherichia
      coli, Enterobacter cloacae and Salmonella paratyphi, while the Lys-Val-Ile-Ser
      Met-Ile peptide shows not only bacterial growth inhibition but also of fungi.
      Haemolytic testing suggested that these two antimicrobial peptides could be
      considered to have no haemolytic effect at their minimum inhibitory
      concentrations (MICs).

PMID- 29210029
TI  - Photoacoustic spectroscopy applied to the direct detection of bioactive compounds
      in Agaricus brasiliensis mycelium.
AB  - This paper describes the application of the photoacoustic spectroscopic (PAS) for
      detection of bioactive compounds in Agaricus brasiliensis mycelium. The mycelium
      was cultivated by solid-state fermentation and by submerged fermentation. Vegetal
      residues from food industry were used as substrates for fermentation: apple
      pomace (Malus domestica), wheat (Triticum aestivum), peel and pomace of pineapple
      (Ananas comosus), malt (Hordeum vulgare) and grape pomace (Vitis vinifera). Dry
      and ground samples of biomass were directly put into the PA cell. The optical
      absorption spectra indicated the existence of three main absorption bands: one
      around 280 nm related to phytosterols (ergosterol), phenolic acids, flavonoids
      and aromatic amino acids, another at 340 nm, due to phenolic and flavonoid
      compounds, and the third one at around 550 nm associated with anthocyanins and
      anthocyanidins. A correlation between the PA signal and the total phenolic
      content was satisfactory, as well as for the analyzed spectrum region (270 nm up
      to 1000 nm), using multivariate methods. Our results indicated that PA technique
      may be considered as an analytical tool to quickly detect bioactive compounds in
      mushrooms without the need of sample pretreatment.

PMID- 29210031
TI  - Adjuvant Statin Therapy for Esophageal Adenocarcinoma: A Cost-Utility Analysis.
AB  - BACKGROUND: Emerging preclinical evidence indicates statins, medications commonly
      used in the prevention of cardiovascular disease (CVD), inhibit proliferation,
      promote apoptosis and limit invasiveness of esophageal adenocarcinoma (EAC).
      Population-based observational data demonstrate statin treatment after diagnosis
      of EAC is associated with significant reductions in all-cause and cancer-specific
      mortality. A feasibility study of adjuvant statin therapy following potentially
      curative resection for EAC has been completed, with planned progression to a full
      phase III, randomized controlled trial. OBJECTIVE: The aim was to estimate the
      cost-utility of statin therapy following surgical resection for EAC from a UK
      National Health Service (NHS) perspective. METHODS: A Markov model was developed
      to estimate the costs and outcomes [quality-adjusted life years (QALYs)] for
      hypothetical cohorts of patients with EAC exposed or not exposed to statins
      following potentially curative surgical resection. Model parameters were based on
      estimates from published observational and trial data. Costs, utilities and
      transition probabilities were modeled to reflect clinical practice from a payer's
      perspective. Probabilistic and one-way sensitivity analyses were performed to
      account for uncertainty in key parameters. RESULTS: Overall, a cost saving of
      L6781 per patient was realized with statin treatment compared to no statins. In
      probabilistic sensitivity analysis, 99% of all iterations were cost saving and
      99% of all iterations were less than L20,000 per QALY gained. These results were
      robust to changes in the price and effectiveness of statins. CONCLUSIONS: The
      cohort exposed to statins had lower costs and better QALY outcomes than the no
      statin cohort. Assuming a causal improvement in disease outcomes following
      resection for EAC, statin therapy is very likely to be a cost-saving treatment.

PMID- 29210032
TI  - Seeking and reporting apparent research misconduct: errors and integrity - a
      reply.

PMID- 29210030
TI  - Pharmacologic prevention of variceal bleeding and rebleeding.
AB  - BACKGROUND: Variceal bleeding is a major complication of portal hypertension,
      which is associated with significant mortality. Moreover, patients surviving a
      variceal bleeding episode have very high risk of rebleeding, which is associated
      with mortality as high as that of the first bleed. Because of this, prevention of
      bleeding from gastroesophageal varices has been one of the main therapeutic goals
      since the advent of the first effective therapies for portal hypertension. AIM:
      This review deals with the present day state-of-the-art pharmacological
      prevention of variceal bleeding in primary and secondary prophylaxis. RESULTS:
      Pharmacological therapy aims to decrease portal pressure (PP) by acting on the
      pathophysiological mechanisms of portal hypertension such as increased hepatic
      vascular tone and splanchnic vasodilatation. Propranolol and nadolol block the
      beta-1 in the heart and the peripheral beta-2 adrenergic receptors. Beta-1
      blockade of cardiac receptors reduces heart rate and cardiac output and
      subsequently decreases flow into splanchnic circulation. Beta-2 blockade leads to
      unopposed alpha-1 adrenergic activity that causes splanchnic vasoconstriction and
      reduction of portal inflow. Both effects contribute to reduction in PP.
      Carvedilol is more powerful in reducing hepatic venous pressure gradient (HVPG)
      than traditional nonselective beta-blockers (NSBBs) and achieves good hemodynamic
      response in nearly 75 % of cases. Simvastatin and atorvastatin improve
      endothelial dysfunction mainly by enhancing endothelial nitric oxide synthase
      (eNOS) expression and phosphorylation and NO production. In addition, statins
      deactivate hepatic stellate cells and ameliorate hepatic fibrogenesis. These
      effects cause a decrease in HVPG and improve liver microcirculation and
      hepatocyte perfusion in patients with cirrhosis. In addition, several promising
      drugs under development may change the management of portal hypertension in the
      coming years. CONCLUSION: This review provides a background on the most important
      aspects of the treatment of portal hypertension in patients with compensated and
      decompensated liver cirrhosis. However, despite the great improvement in the
      prevention of variceal bleeding over the last years, further therapeutic options
      are needed.

PMID- 29210033
TI  - Strategies for the prevention of airway complications - a narrative review.
AB  - Despite being infrequent, complications of airway management remain an important
      contributor to morbidity and mortality during anaesthesia and care of the
      critically ill. Developments in the last three decades have made anaesthesia
      safer, and this has been mirrored in the equipment and techniques available for
      airway management. Modern technology including novel oxygenation modalities,
      widespread availability of capnography, second-generation supraglottic airway
      devices and videolaryngoscopy provide the tools to make airway management safer
      still. However, technology will only take safety so far, and non-technical
      aspects of airway management are critically important for communication and
      decision making during airway crises, acknowledging a 'cannot intubate, cannot
      oxygenate' situation and transitioning to emergency front of neck airway.
      Randomised controlled trials provide little useful information about safety in
      this setting, and data from registries and databases are likely to be of more
      value. This narrative review focuses on recent evidence in this area.

PMID- 29210034
TI  - A novel wheeze.

PMID- 29210035
TI  - Seeking and reporting apparent research misconduct: errors and integrity - a
      reply.

PMID- 29210036
TI  - Moderate vs. deep neuromuscular blockade and monitoring.

PMID- 29210037
TI  - Medical gas cylinder expiry dates - a reply.

PMID- 29210038
TI  - Sugammadex advice for women of childbearing age.

PMID- 29210039
TI  - Seeking and reporting apparent research misconduct: errors and integrity.

PMID- 29210040
TI  - Patient emergence - statistical questions.

PMID- 29210042
TI  - Medical gas cylinder expiry dates.

PMID- 29210041
TI  - Coding for anaesthetic and peri-operative practice.

PMID- 29210044
TI  - Patient emergence - statistical questions: a reply.

PMID- 29210045
TI  - Surgery or in vitro fertilization: The simplicity of this question belies its
      complexity.
AB  - Unlike surgery, assisted reproduction, particularly in vitro fertilisation (IVF),
      requires a low skill base, is largely practitioner independent, is highly
      effective, quality controlled, reproducible and consistent in the management of
      endometriosis-associated infertility. Ultimately, however, the decision to
      proceed to IVF or surgery is dependent on the woman, her reproductive
      expectations, her specific disease pattern, her support and family network and
      the resources available in a given health care setting.

PMID- 29210043
TI  - Accidental awareness during general anaesthesia - a narrative review.
AB  - Unintended accidental awareness during general anaesthesia represents failure of
      successful anaesthesia, and so has been the subject of numerous studies during
      the past decades. As return to consciousness is both difficult to describe and
      identify, the reported incidence rates vary widely. Similarly, a wide range of
      techniques have been employed to identify cases of accidental awareness. Studies
      which have used the isolated forearm technique to identify responsiveness to
      command during intended anaesthesia have shown remarkably high incidences of
      awareness. For example, the ConsCIOUS-1 study showed an incidence of
      responsiveness around the time of laryngoscopy of 1:25. On the other hand, the
      5th Royal College of Anaesthetists National Audit Project, which reported the
      largest ever cohort of patients who had experienced accidental awareness, used a
      system to identify patients who spontaneously self-reported accidental awareness.
      In this latter study, the incidence of accidental awareness was 1:19,600. In the
      recently published SNAP-1 observational study, in which structured postoperative
      interviews were performed, the incidence was 1:800. In almost all reported cases
      of intra-operative responsiveness, there was no subsequent explicit recall of
      intra-operative events. To date, there is no evidence that this occurrence has
      any psychological consequences. Among patients who experience accidental
      awareness and can later remember details of their experience, the consequences
      are better known. In particular, when awareness occurs in a patient who has been
      given neuromuscular blocking agents, it may result in serious sequelae such as
      symptoms of post-traumatic stress disorder and a permanent aversion to surgery
      and anaesthesia, and is feared by patients and anaesthetists. In this article,
      the published literature on the incidence, consequences and management of
      accidental awareness under general anaesthesia with subsequent recall will be
      reviewed.

PMID- 29210047
TI  - Re. recent publications by Adams et al. and Biro et al.

PMID- 29210048
TI  - Authors' reply.

PMID- 29210049
TI  - Reply to 'Response to Current barriers and potential strategies to increase the
      use of long-acting reversible contraception (LARC) to reduce the rate of
      unintended pregnancies in Australia: An expert roundtable discussion'.

PMID- 29210050
TI  - In response to: Current barriers and potential strategies to increase the use of
      long-acting reversible contraception to reduce the rate of unintended pregnancies
      in Australia: An expert roundtable discussion.

PMID- 29210051
TI  - Authors' reply.

PMID- 29210052
TI  - Neoadjuvant chemotherapy for advanced epithelial ovarian cancer. Who really
      benefits?

PMID- 29210053
TI  - Food groups and risk of colorectal cancer.
AB  - The aim of this systematic review and meta-analysis was to summarize the evidence
      on the relationship between intake of 12 major food groups, including whole
      grains, refined grains, vegetables, fruit, nuts, legumes, eggs, dairy, fish, red
      meat, processed meat and sugar-sweetened beverages with risk of colorectal cancer
      (CRC). We conducted a systematic search in PubMed and Embase for prospective
      studies investigating the association between these 12 food groups and risk of
      CRC until April 2017. Summary risk ratios (RRs) and 95% confidence intervals (95%
      CI) were estimated using a random effects model for high vs. low intake
      categories, as well as for linear and nonlinear relationships. An inverse
      association was observed for whole grains (RR30g/d : 0.95, 95% CI 0.93, 0.97; n =
      9 studies), vegetables (RR100g/d : 0.97, 95% CI 0.96, 0.98; n = 15), fruit
      (RR100g/d : 0.97, 95% CI 0.95, 0.99; n = 16) and dairy (RR200g/d : 0.93, 95% CI
      0.91, 0.94; n = 15), while a positive association for red meat (RR100g/d : 1.12,
      95% CI 1.06, 1.19; n = 21) and processed meat (RR50g/d : 1.17, 95% CI 1.10, 1.23;
      n = 16), was seen in the linear dose-response meta-analysis. Some evidence for
      nonlinear relationships was observed between vegetables, fruit and dairy and risk
      of colorectal cancer. Findings of this meta-analysis showed that a diet
      characterized by high intake of whole grains, vegetables, fruit and dairy
      products and low amounts of red meat and processed meat was associated with lower
      risk of CRC.

PMID- 29210054
TI  - A comparison of DSM-5 and ICD-11 PTSD prevalence, comorbidity and disability: an
      analysis of the Ukrainian Internally Displaced Person's Mental Health Survey.
AB  - OBJECTIVE: Recently, the American Psychiatric Association (DSM-5) and the World
      Health Organization (ICD-11) have both revised their formulation of post
      traumatic stress disorder (PTSD). The primary aim of this study was to compare
      DSM-5 and ICD-11 PTSD prevalence and comorbidity rates, as well as the level of
      disability associated with each diagnosis. METHOD: This study was based on a
      representative sample of adult Ukrainian internally displaced persons (IDPs: N =
      2203). Post-traumatic stress disorder prevalence was assessed using the PTSD
      Checklist for DSM-5 and the International Trauma Questionnaire (ICD-11). Anxiety
      and depression were measured using the Generalized Anxiety Disorder Scale and the
      Patient Health Questionnaire-Depression. Disability was measured using the WHO
      Disability Assessment Schedule 2.0. RESULTS: The prevalence of DSM-5 PTSD (27.4%)
      was significantly higher than ICD-11 PTSD (21.0%), and PTSD rates for females
      were significantly higher using both criteria. ICD-11 PTSD was associated with
      significantly higher levels of disability and comorbidity. CONCLUSION: The ICD-11
      diagnosis of PTSD appears to be particularly well suited to identifying those
      with clinically relevant levels of disability.

PMID- 29210055
TI  - Patient-Centered Reverse Translation.

PMID- 29210056
TI  - Utility of a Precision Medicine Test in Elderly Adults with Symptoms Suggestive
      of Coronary Artery Disease.
AB  - BACKGROUND: Diagnosing obstructive coronary artery disease (CAD) is challenging
      in elderly adults, and current diagnostic approaches for CAD expose these
      individuals to risks from contrast dye and invasive procedures. DESIGN: A
      Registry to Evaluate Patterns of Care Associated with the Use of Corus CAD in
      Real World Clinical Care Settings (PRESET; NCT01677156), pragmatic clinical
      trial. SETTING: Community, 21 primary care practices. PARTICIPANTS: Of 566
      stable, nonacute outpatients presenting with symptoms suggestive of obstructive
      CAD, the 176 who were aged 65 and older (median age 70, 61% female) were the
      current study participants. INTERVENTION: Blood-based precision medicine test,
      incorporating age, sex, and gene expression score (ASGES) to improve clinical
      decision-making and quality of care. MEASUREMENTS: Information on demographic
      characteristics, clinical factors, ASGES results (range 1-40; low (<=15), high
      (>15)), referral patterns to cardiology and advanced cardiac testing, and major
      adverse cardiac events (MACEs) was collected in a subgroup analysis of elderly
      adults in the PRESET Registry. Follow-up was for 1 year after ASGES testing.
      RESULTS: Median ASGES was 25, and 40 (23%) participants had a low score.
      Clinicians referred 12.5% of participants with a low ASGES and 49.3% with a high
      ASGES to cardiology or advanced cardiac testing (odds ratio for referral = 0.12,
      P < .001, adjusted for participants demographics and clinical covariates). Higher
      scores were associated with greater likelihood of posttest cardiac referral. At 1
      year follow-up, the incidence of a MACE or revascularization was 10% (13/136) in
      the high ASGES group and 0% (0/40) in the low ASGES group (P = .04). CONCLUSION:
      The ASGES test showed potential clinical utility in the evaluation of elderly
      outpatients with symptoms suggestive of obstructive CAD. Test use may reduce
      unnecessary referrals and the risk of procedure-related complications in
      individuals with low ASGES, who are unlikely to benefit from further testing,
      while also identifying individuals who may benefit from further cardiac
      evaluation and management.

PMID- 29210057
TI  - A functional polymorphism in TFF1 promoter is associated with the risk and
      prognosis of gastric cancer.
AB  - Trefoil Factor 1 (TFF1, also named pS2), which serves as the gastrointestinal
      mucosal protector, is known as gastric-specific tumor suppressor gene. However,
      the genetic variants of TFF1 are still not well studied. In our study, we aim to
      explore the effects of tagging single nucleotide polymorphisms (tagSNPs) of TFF1
      on risk and prognosis of gastric cancer. Seven tagSNPs of TFF1 gene were first
      analyzed in the discovery set, which was consisted of 753 cases and 950 cancer
      free controls. Then, the validation set (940 cases and 1,042 controls) was used
      for further evaluation. Moreover, we also tested the relation between these
      tagSNPs and prognosis of gastric cancer (GC). A series of experiments were
      performed to investigate the underlying mechanisms. We found that rs3761376 AA in
      the promoter region of TFF1, could reduce the expression of TFF1 by affecting the
      binding affinity of estrogen receptor 1 (ESR1, ERalpha), and thereby increased
      the risk of GC (1.29, 1.08-1.53). Moreover, the rs3761376 AA genotype was also
      found associated with worse prognosis among patients receiving 5-FU based
      chemotherapy after surgery (1.71, 1.18-2.48). Further functional assays
      demonstrated that TFF1 could increase the chemosensitivity of 5-FU by modulating
      NF-kappaB targeted genes. These results identified the effect of rs3761376 on
      TFF1 expression, which accounted for the correlation with susceptibility and
      prognosis of GC; and this genetic variant may be a potential biomarker to predict
      the risk and survival of GC.

PMID- 29210058
TI  - Development and internal validation of the Simplified Mortality Score for the
      Intensive Care Unit (SMS-ICU).
AB  - BACKGROUND: Intensive care unit (ICU) mortality prediction scores deteriorate
      over time, and their complexity decreases clinical applicability and commonly
      causes problems with missing data. We aimed to develop and internally validate a
      new and simple score that predicts 90-day mortality in adults upon acute
      admission to the ICU: the Simplified Mortality Score for the Intensive Care Unit
      (SMS-ICU). METHODS: We used data from an international cohort of 2139 patients
      acutely admitted to the ICU and 1947 ICU patients with severe sepsis/septic shock
      from 2009 to 2016. We performed multiple imputations for missing data and used
      binary logistic regression analysis with variable selection by backward
      elimination, followed by conversion to a simple point-based score. We assessed
      the apparent performance and validated the score internally using bootstrapping
      to present optimism-corrected performance estimates. RESULTS: The SMS-ICU
      comprises seven variables available in 99.5% of the patients: two numeric
      variables: age and lowest systolic blood pressure, and five dichotomous
      variables: haematologic malignancy/metastatic cancer, acute surgical admission
      and use of vasopressors/inotropes, respiratory support and renal replacement
      therapy. Discrimination (area under the receiver operating characteristic curve)
      was 0.72 (95% CI: 0.71-0.74), overall performance (Nagelkerke's R2 ) was 0.19 and
      calibration (intercept and slope) was 0.00 and 0.99, respectively. Optimism
      corrected performance was similar to apparent performance. CONCLUSIONS: The SMS
      ICU predicted 90-day mortality with reasonable and stable performance. If
      performance remains adequate after external validation, the SMS-ICU could prove a
      valuable tool for ICU clinicians and researchers because of its simplicity and
      expected very low number of missing values.

PMID- 29210059
TI  - Ezrin mediates both HGF/Met autocrine and non-autocrine signaling-induced
      metastasis in melanoma.
AB  - Aberrant HGF/Met signaling promotes tumor migration, invasion, and metastasis
      through both autocrine and non-autocrine mechanisms; however, the molecular
      downstream signaling mechanisms by which HGF/Met induces metastasis are
      incompletely understood. We here report that Ezrin expression is stimulated by
      HGF and correlates with activated HGF/Met, indicating that HGF/Met signaling
      regulates the expression of Ezrin. We show that HGF/Met signaling activates the
      transcription factor Sp1 through the MAPK pathway, and activated Sp1 can in turn
      directly bind to the promoter of Ezrin gene and regulate its transcription.
      Notably, knockdown of Ezrin expression by shRNAs inhibits the metastasis induced
      by either HGF/Met autocrine or non-autocrine signaling in syngeneic wildtype and
      HGF transgenic mouse hosts. We also used small molecule drugs in preclinical
      mouse models to confirm that Ezrin is one of the downstream molecules mediating
      HGF/Met signaling-induced metastasis in melanoma. We conclude that Ezrin is a key
      downstream factor involved in the regulation of HGF/Met signaling-induced
      metastasis and demonstrate a link between Ezrin and HGF/Met/MAPK/Sp1 activation
      in the metastatic process. Our data indicate that Ezrin represents a promising
      therapeutic target for patients bearing tumors with activated HGF/Met signaling.

PMID- 29210061
TI  - The association with cardiovascular disease and type 2 diabetes in adults with
      atopic dermatitis: a systematic review and meta-analysis.
AB  - BACKGROUND: Recent studies examining the association between atopic dermatitis
      (AD) and cardiovascular disease (CVD) and type 2 diabetes have shown inconsistent
      results. OBJECTIVES: To carry out a systematic review and meta-analysis that
      examines the association with cardiovascular disease and type 2 diabetes in
      adults with AD. METHODS: We compared the risk of CVD and diabetes for adult
      patients with and without AD by searching the PubMed, Embase and Web of Science
      databases. Data extraction was carried out by two independent reviewers. We found
      a total of 2855 citations, of which 53 were considered relevant based on title
      and abstract. Overall, 16 publications were included in the qualitative analysis,
      of which 13 were also included in a quantitative meta-analysis of crude data.
      RESULTS: No association was observed between AD and unspecified but suspected
      type 2 diabetes [pooled odds ratio (OR) 1.11; 95% confidence interval (CI) 0.87
      1.42], hypertension (pooled OR 1.16; 95% CI 0.98-1.37), stroke (pooled OR 1.15;
      95% CI 0.95-1.39) or myocardial infarction (pooled OR 1.14; 95% CI 0.83-1.56),
      but a positive association was observed with angina pectoris (OR 1.73; 95% CI
      1.27-2.37). Meta-analysis of adjusted data gave similar results. CONCLUSIONS:
      While adults with AD in some populations have an increased prevalence of
      cardiovascular risk factors, such as obesity and smoking, it is unlikely that AD
      represents an independent and clinically relevant risk factor for cardiometabolic
      disease.

PMID- 29210062
TI  - Incidence of hyperoxia and related in-hospital mortality in critically ill
      patients: a retrospective data analysis.
AB  - BACKGROUND: Mechanical ventilation with oxygen is life-saving, however, may
      result in hyperoxia. The aim was to analyse the incidence and duration of
      hyperoxia burden and related in-hospital mortality in critically ill patients.
      METHODS: Patients of all ages admitted to intensive care units (ICUs) and with
      mechanical ventilation for at least seven consecutive days were included in this
      single centre retrospective medical record audit. The main outcome measure was
      time-weighted arterial partial pressure of oxygen (PaO2 ) over 7 days. Logistic
      regression for association with in-hospital mortality and propensity score
      matching was performed. RESULTS: In total, 20,889 arterial blood gases of 419
      patients were analysed. Time-weighted mean PaO2 was 14.0 +/- 2.4 kPa. Time
      weighted mean FiO2 was 49.2 +/- 12.1%. Seventy-six (18.1%) patients showed
      continuous hyperoxia exposure, defined as time-weighted mean PaO2 > 16 kPa.
      Duration of hyperoxia, hypoxia (PaO2 < 8 kPa) and normoxia (PaO2 8-16 kPa) were
      37.9 +/- 31.0 h (23.7%), 4.9 +/- 9.5 h (3.1%), and 116.8 +/- 29.6 h (73.2%).
      Hyperoxia occurred especially at low to moderate FiO2 in patients of first and
      second age quartiles (1-57 years) with smaller SAPS2 score. In-hospital mortality
      of patients with hyperoxia (32.9%) or normoxia did not differ (35.9%; P = 0.691).
      Conditional logistic regression showed no association between hyperoxia and in
      hospital mortality (OR 1.46; 95%CI 0.72-2.96; P = 0.29). CONCLUSION: Substantial
      hyperoxia burden was observed in ICU patients. Young patients with less
      comorbidities showed hyperoxic episodes more often, especially with lower FiO2 .
      Hyperoxia during 7 days of mechanical ventilation did not correlate to increased
      in-hospital mortality.

PMID- 29210060
TI  - Genome-wide association study identifies the GLDC/IL33 locus associated with
      survival of osteosarcoma patients.
AB  - Survival rates for osteosarcoma, the most common primary bone cancer, have
      changed little over the past three decades and are particularly low for patients
      with metastatic disease. We conducted a multi-institutional genome-wide
      association study (GWAS) to identify germline genetic variants associated with
      overall survival in 632 patients with osteosarcoma, including 523 patients of
      European ancestry and 109 from Brazil. We conducted a time-to-event analysis and
      estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox
      proportional hazards models, with and without adjustment for metastatic disease.
      The results were combined across the European and Brazilian case sets using a
      random-effects meta-analysis. The strongest association after meta-analysis was
      for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR
      = 1.76; 95% CI 1.41-2.18, p = 4.84 * 10-7 ). After imputation across this region,
      the combined analysis identified two SNPs that reached genome-wide significance.
      The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p
      = 1.3 * 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and
      was consistent across both the European and Brazilian case sets. Using publicly
      available data, the risk allele was associated with lower expression of IL33 and
      low expression of IL33 was associated with poor survival in an independent set of
      patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus
      on chromosome 9p24.1 as associated with overall survival in patients with
      osteosarcoma. Further studies are needed to confirm this association and shed
      light on the biological underpinnings of this susceptibility locus.

PMID- 29210064
TI  - Normothermic machine perfusion for the assessment and transplantation of declined
      human kidneys from donation after circulatory death donors.
AB  - BACKGROUND: A significant proportion of donation after circulatory death (DCD)
      kidneys are declined for transplantation because of concerns over their quality.
      Ex vivo normothermic machine perfusion (NMP) provides a unique opportunity to
      assess the quality of a kidney and determine its suitability for transplantation.
      METHODS: In phase 1 of this study, declined human DCD kidneys underwent NMP
      assessment for 60 min. Kidneys were graded 1-5 using a quality assessment score
      (QAS) based on macroscopic perfusion, renal blood flow and urine output during
      NMP. In phase 2 of the study, declined DCD kidneys were assessed by NMP with an
      intention to transplant them. RESULTS: In phase 1, 18 of 42 DCD kidneys were
      declined owing to poor in situ perfusion. After NMP, 28 kidneys had a QAS of 1-3,
      and were considered suitable for transplantation. In phase 2, ten of 55 declined
      DCD kidneys underwent assessment by NMP. Eight kidneys had been declined because
      of poor in situ flushing in the donor and five of these were transplanted
      successfully. Four of the five kidneys had initial graft function. CONCLUSION:
      NMP technology can be used to increase the number of DCD kidney transplants by
      assessing their quality before transplantation.

PMID- 29210063
TI  - Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in
      vitro: link to clinical reports of serotonin syndrome.
AB  - BACKGROUND AND PURPOSE: Opioids may inhibit the 5-HT transporter (SERT) and the
      noradrenaline transporter (NET). NET inhibition may contribute to analgesia, and
      SERT inhibition or interactions with 5-HT receptors may cause serotonergic
      toxicity. However, the effects of different opioids on the human SERT, NET and 5
      HT receptors have not been sufficiently studied. EXPERIMENTAL APPROACH: We
      determined the potencies of different opioids to inhibit the SERT and NET in
      vitro using human transporter-transfected HEK293 cells. We also tested binding
      affinities at 5-HT1A , 5-HT2A and 5-HT2C receptors. Additionally, we assessed
      clinical cases of the serotonin syndrome associated with each opioid reported by
      PubMed and a World Health Organization database. KEY RESULTS: Dextromethorphan,
      l(R)-methadone, racemic methadone, pethidine, tramadol and tapentadol inhibited
      the SERT at or close to observed drug plasma or estimated brain concentrations in
      patients. Tapentadol was the most potent NET inhibitor. Pethidine, tramadol, l(R)
      methadone, racemic methadone, dextromethorphan and O-desmethyltramadol also
      inhibited the NET. 6-Monoacetylmorphine, buprenorphine, codeine, dihydrocodeine,
      heroin, hydrocodone, hydromorphone, morphine, oxycodone and oxymorphone did not
      inhibit the SERT or NET. Fentanyl interacted with 5-HT1A receptors and methadone,
      pethidine and fentanyl with 5-HT2A receptors, in the low micromolar range.
      Opioids most frequently associated with the serotonin syndrome are tramadol,
      fentanyl, tapentadol, oxycodone, methadone and dextromethorphan. CONCLUSIONS AND
      IMPLICATIONS: Some synthetic opioids interact with the SERT and NET at
      potentially clinically relevant concentrations. SERT inhibition by tramadol,
      tapentadol, methadone, dextromethorphan and pethidine may contribute to the
      serotonin syndrome. Direct effects on 5-HT1A and/or 5-HT2A receptors could be
      involved with methadone and pethidine.

PMID- 29210065
TI  - HDAC inhibitors restore BRAF-inhibitor sensitivity by altering PI3K and survival
      signalling in a subset of melanoma.
AB  - Mutations in BRAF activate oncogenic MAPK signalling in almost half of cutaneous
      melanomas. Inhibitors of BRAF (BRAFi) and its target MEK are widely used to treat
      melanoma patients with BRAF mutations but unfortunately acquired resistance
      occurs in the majority of patients. Resistance results from mutations or non
      genomic changes that either reactivate MAPK signalling or activate other pathways
      that provide alternate survival and growth signalling. Here, we show the histone
      deacetylase inhibitor (HDACi) panobinostat overcomes BRAFi resistance in
      melanoma, but this is dependent on the resistant cells showing a partial response
      to BRAFi treatment. Using patient- and in vivo-derived melanoma cell lines with
      acquired BRAFi resistance, we show that combined treatment with the BRAFi
      encorafenib and HDACi panobinostat in 2D and 3D culture systems synergistically
      induced caspase-dependent apoptotic cell death. Key changes induced by HDAC
      inhibition included decreased PI3K pathway activity associated with a reduction
      in the protein level of a number of receptor tyrosine kinases, and cell line
      dependent upregulation of pro-apoptotic BIM or NOXA together with reduced
      expression of anti-apoptotic proteins. Independent of these changes, panobinostat
      reduced c-Myc and pre-treatment of cells with siRNA against c-Myc reduced
      BRAFi/HDACi drug-induced cell death. These results suggest that a combination of
      HDAC and MAPK inhibitors may play a role in treatment of melanoma where the
      resistance mechanisms are due to activation of MAPK-independent pathways.

PMID- 29210066
TI  - The interictal mesial temporal lobe epilepsy network.
AB  - OBJECTIVE: Identification of patient-specific epileptogenic networks is critical
      to designing successful treatment strategies. Multiple noninvasive methods have
      been used to characterize epileptogenic networks. However, these methods lack the
      spatiotemporal resolution to allow precise localization of epileptiform activity.
      We used intracranial recordings, at much higher spatiotemporal resolution, across
      a cohort of patients with mesial temporal lobe epilepsy (MTLE) to delineate
      features common to their epileptogenic networks. We used interictal rather than
      seizure data because interictal spikes occur more frequently, providing us
      greater power for analyzing variances in the network. METHODS: Intracranial
      recordings from 10 medically refractory MTLE patients were analyzed. In each
      patient, hour-long recordings were selected for having frequent interictal
      discharges and no ictal events. For all possible pairs of electrodes, conditional
      probability of the occurrence of interictal spikes within a 150-millisecond bin
      was computed. These probabilities were used to construct a weighted graph between
      all electrodes, and the node degree was estimated. To assess the relationship of
      the highly connected regions in this network to the clinically identified seizure
      network, logistic regression was used to model the regions that were surgically
      resected using weighted node degree and number of spikes in each channel as
      factors. Lastly, the conditional spike probability was normalized and averaged
      across patients to visualize the MTLE network at group level. RESULTS: We
      generated the first graph of connectivity across a cohort of MTLE patients using
      interictal activity. The most consistent connections were hippocampus to
      amygdala, anterior fusiform cortex to hippocampus, and parahippocampal gyrus
      projections to amygdala. Additionally, the weighted node degree and number of
      spikes modeled the brain regions identified as seizure networks by clinicians.
      SIGNIFICANCE: Apart from identifying interictal measures that can model patient
      specific epileptogenic networks, we also produce a group map of network
      connectivity from a cohort of MTLE patients.

PMID- 29210067
TI  - Biomarkers of acute kidney injury - a mission impossible?

PMID- 29210068
TI  - Optimal Storage Conditions for Apheresis Research (OSCAR): a Biomedical
      Excellence for Safer Transfusion (BEST) Collaborative study.
AB  - BACKGROUND: Cell therapy products are often stored and transported between sites.
      The aim of this study was to determine the effect of storage temperature,
      solution, and cell concentration on nonmobilized, peripheral blood-derived
      mononuclear cells (MNCs). STUDY DESIGN AND METHODS: This was a multicenter
      prospective study involving healthy volunteers who underwent nonmobilized MNC
      collection by apheresis. Products were processed at local laboratories and
      concentrated to either 100 * 106 or 300 * 106 nucleated cells/mL in 5% human
      serum albumin (HSA) or HypoThermosol FRS (HT; BioLife Solutions). Products were
      stored at room temperature (RT; 20-25 degrees C) or refrigerated temperatures (2
      8 degrees C) with assessment at 0, 24, 48, and 72 hours. NC and MNC
      concentration, viability, and flow cytometric analysis for CD3, CD4, CD8, CD14,
      CD19, CD25, and CD56 were measured. RESULTS: Viability decreased over time for
      all conditions tested. Refrigerated storage preserved viability greater than RT
      storage, especially for products with a higher cell concentration. RT maintenance
      with a high cell concentration was associated with a relative loss of CD14- and
      CD4-positive cells, whereas the concentration of cells positive for other markers
      tested did not vary. Finally, there was delayed decrease in pH when using HT
      compared with HSA; however, there was no difference in viability between the two
      solutions. CONCLUSION: Low cell concentrations (approx. 100 * 106 cells/mL),
      refrigerated temperatures, and HT storage solution appear to be the optimal
      conditions for storing nonmobilized, peripheral blood-derived MNC products.

PMID- 29210069
TI  - Ageing-induced internalization and degradation of VE-cadherin leads to vascular
      dysfunction.

PMID- 29210070
TI  - Dynamic interplay between photodamage and photoprotection in photosystem II.
AB  - Photoinhibition is the light-induced reduction in photosynthetic efficiency and
      is usually associated with damage to the D1 photosystem II (PSII) reaction centre
      protein. This damage must either be repaired, through the PSII repair cycle, or
      prevented in the first place by nonphotochemical quenching (NPQ). Both NPQ and D1
      repair contribute to light tolerance because they ensure the long-term
      maintenance of the highest quantum yield of PSII. However, the relative
      contribution of each of these processes is yet to be elucidated. The application
      of a pulse amplitude modulation fluorescence methodology, called protective NPQ,
      enabled us to evaluate of the protective effectiveness of the processes. Within
      this study, the contribution of NPQ and D1 repair to the photoprotective capacity
      of Arabidopsis thaliana was elucidated by using inhibitors and mutants known to
      affect each process. We conclude that NPQ contributes a greater amount to the
      maintenance of a high PSII yield than D1 repair under short periods of
      illumination. This research further supports the role of protective components of
      NPQ during light fluctuations and the value of protective NPQ and qPd as
      unambiguous fluorescence parameters, as opposed to qI and Fv /Fm , for
      quantifying photoinactivation of reaction centre II and light tolerance of
      photosynthetic organisms.

PMID- 29210071
TI  - Whole-exome sequencing of sickle cell disease patients with hyperhemolysis
      syndrome suggests a role for rare variation in disease predisposition.
AB  - BACKGROUND: Hyperhemolysis syndrome (HHS) is an uncommon, but life-threatening,
      transfusion-related complication of red blood cell transfusion. HHS has
      predominantly been described in patients with sickle cell disease (SCD) and is
      difficult to diagnose and treat. The pathogenesis of HHS, including its
      occurrence in only a subset of apparently susceptible individuals, is poorly
      understood. We undertook whole-exome sequencing (WES) of 12 SCD-HHS patients to
      identify shared genetic variants that might be relevant to the development of
      HHS. STUDY DESIGN AND METHODS: DNA from adults with SCD having at least one
      previous episode of HHS were subject to WES. High-quality variants were passed
      through a series of bioinformatics filters to identify variants that were
      uncommon among African populations represented in public databases. Recurrent,
      putative loss-of-function variants occurring in biologically plausible genes were
      prioritized and then genotyped in a larger, ancestry-matched cohort of non-HHS
      controls. RESULTS: A rare, heterozygous stop-gain variant (p.Glu210Ter) in MBL2
      was significantly enriched among HHS cases (p = 0.002). This variant is predicted
      to result in a premature termination codon that escapes nonsense-mediated mRNA
      decay, potentially leading to a novel phenotype. We also observed a complex
      insertion-deletion variant in the final exon of KLRC3 that was enriched among
      cases (p = 0.0019), although neither variant was found among seven pediatric SCD
      HHS patients. CONCLUSION: Our results suggest a potential role for rare genetic
      defects in the development of HHS among adult SCD patients. Such enriched
      variants may ultimately be useful for identifying high-risk individuals and
      informing therapeutic approaches in HHS.

PMID- 29210072
TI  - Chemical hypoxia-induced integrated stress response activation in
      oligodendrocytes is mediated by the transcription factor nuclear factor
      (erythroid-derived 2)-like 2 (NRF2).
AB  - The extent of remyelination in multiple sclerosis lesions is often incomplete.
      Injury to oligodendrocyte progenitor cells can be a contributing factor for such
      incomplete remyelination. The precise mechanisms underlying insufficient repair
      remain to be defined, but oxidative stress appears to be involved. Here, we used
      immortalized oligodendrocyte cell lines as model systems to investigate a causal
      relation of oxidative stress and endoplasmic reticulum stress signaling cascades.
      OLN93 and OliNeu cells were subjected to chemical hypoxia by blocking the
      respiratory chain at various levels. Mitochondrial membrane potential and
      oxidative stress levels were quantified by flow cytometry. Endoplasmic reticulum
      stress was monitored by the expression induction of activating transcription
      factor 3 and 4 (Atf3, Atf4), DNA damage-inducible transcript 3 protein (Ddit3),
      and glucose-regulated protein 94. Lentiviral silencing of nuclear factor
      (erythroid-derived 2)-like 2 or kelch-like ECH-associated protein 1 was applied
      to study the relevance of NRF2 for endoplasmic reticulum stress responses. We
      demonstrate that inhibition of the respiratory chain induces oxidative stress in
      cultured oligodendrocytes which is paralleled by the expression induction of
      distinct mediators of the endoplasmic reticulum stress response, namely Atf3,
      Atf4, and Ddit3. Atf3 and Ddit3 expression induction is potentiated in kelch-like
      ECH-associated protein 1-deficient cells and absent in cells lacking the
      oxidative stress-related transcription factor NRF2. This study provides strong
      evidence that oxidative stress in oligodendrocytes activates endoplasmic
      reticulum stress response in a NRF2-dependent manner and, in consequence, might
      regulate oligodendrocyte degeneration in multiple sclerosis and other
      neurological disorders.

PMID- 29210074
TI  - White matter degeneration in vascular and other ageing-related dementias.
AB  - Advances in neuroimaging have enabled greater understanding of the progression of
      cerebral degenerative processes associated with ageing-related dementias.
      Leukoaraiosis or rarefied white matter (WM) originally described on computed
      tomography is one of the most prominent changes which occurs in older age. White
      matter hyperintensities (WMH) evident on magnetic resonance imaging have become
      commonplace to describe WM changes in relation to cognitive dysfunction, types of
      stroke injury, cerebral small vessel disease and neurodegenerative disorders
      including Alzheimer's disease. Substrates of WM degeneration collectively include
      myelin loss, axonal abnormalities, arteriolosclerosis and parenchymal changes
      resulting from lacunar infarcts, microinfarcts, microbleeds and perivascular
      spacing. WM cells incorporating astrocytes, oligodendrocytes, pericytes and
      microglia are recognized as key cellular components of the gliovascular unit.
      They respond to ongoing pathological processes in different ways leading to
      disruption of the gliovascular unit. The most robust alterations involve
      oligodendrocyte loss and astrocytic clasmatodendrosis with displacement of the
      water channel protein, aquaporin 4. These modifications likely precede
      arteriolosclerosis and capillary degeneration and involve tissue oedema, breach
      of the blood-brain barrier and induction of a chronic hypoxic state in the deep
      WM. Several pathophysiological mechanisms are proposed to explain how WM changes
      commencing with haemodynamic changes within the vascular system impact on
      cognitive dysfunction. Animal models simulating cerebral hypoperfusion in man
      have paved the way for several translational opportunities. Various compounds
      with variable efficacies have been tested to reduce oxidative stress,
      inflammation and blood-brain barrier damage in the WM. Our review demonstrates
      that WM degeneration encompasses multiple substrates and therefore more than one
      pharmacological approach is necessary to preserve axonal function and prevent
      cognitive impairment. This article is part of the Special Issue "Vascular
      Dementia".

PMID- 29210073
TI  - Interleukin-17 regulates matrix metalloproteinase activity in human pulmonary
      tuberculosis.
AB  - Tuberculosis (TB) is characterized by extensive pulmonary matrix breakdown.
      Interleukin-17 (IL-17) is key in host defence in TB but its role in TB-driven
      tissue damage is unknown. We investigated the hypothesis that respiratory stromal
      cell matrix metalloproteinase (MMP) production in TB is regulated by T-helper 17
      (TH -17) cytokines. Biopsies of patients with pulmonary TB were analysed by
      immunohistochemistry (IHC), and patient bronchoalveolar lavage fluid (BALF) MMP
      and cytokine concentrations were measured by Luminex assays. Primary human airway
      epithelial cells were stimulated with conditioned medium from human monocytes
      infected with Mycobacterium tuberculosis (Mtb) and TH -17 cytokines. MMP
      secretion, activity, and gene expression were determined by ELISA, Luminex assay,
      zymography, RT-qPCR, and dual luciferase reporter assays. Signalling pathways
      were examined using phospho-western analysis and siRNA. IL-17 is expressed in TB
      patient granulomas and MMP-3 is expressed in adjacent pulmonary epithelial cells.
      IL-17 had a divergent, concentration-dependent effect on MMP secretion,
      increasing epithelial secretion of MMP-3 (p < 0.001) over 72 h, whilst decreasing
      that of MMP-9 (p < 0.0001); mRNA levels were similarly affected. Both IL-17 and
      IL-22 increased fibroblast Mtb-dependent MMP-3 secretion but IL-22 did not
      modulate epithelial MMP-3 expression. Both IL-17 and IL-22, but not IL-23, were
      significantly up-regulated in BALF from TB patients. IL-17-driven MMP-3 was
      dependent on p38 MAP kinase and the PI3K p110alpha subunit. In summary, IL-17
      drives airway stromal cell-derived MMP-3, a mediator of tissue destruction in TB,
      alone and with monocyte-dependent networks in TB. This is regulated by p38 MAP
      kinase and PI3K pathways. (c) 2017 The Authors. The Journal of Pathology
      published by John Wiley & Sons Ltd on behalf of Pathological Society of Great
      Britain and Ireland.

PMID- 29210075
TI  - Noise contamination from PET blood sampling pump: Effects on structural MRI image
      quality in simultaneous PET/MR studies.
AB  - PURPOSE: To fully quantify PET imaging outcome measures, a blood sampling pump is
      often used during the PET acquisition. With simultaneous PET/MR studies, a
      structural magnetization-prepared rapid gradient-echo (MP-RAGE) may also be
      acquired while the pump is generating electromagnetic noise. This study
      investigated whether this noise contamination would be detrimental to the
      quantification of volume and cortical thickness measures obtained from automated
      segmentation of the MP-RAGE image. METHODS: MP-RAGE T1w structural images were
      acquired for a phantom and 10 healthy volunteers (five female, 27.2 +/- 5.1 y
      old) with the blood sampling pump and without. The white matter signal-to-noise
      ratio (SNR) was computed for all images. Region-wise cortical thickness and
      volume were extracted with Freesurfer 5.3.0. RESULTS: The phantom SNR and the
      white matter human subject SNR was degraded in the MP-RAGE images acquired with
      the pump (P = 0.005; white matter SNR: 43.9 and 50.8 with the pump and without).
      Intrasession, region-wise volume and cortical thickness estimates were
      significantly overestimated with the pump (percent difference: 1.14 +/- 2.67% for
      volume (P = 0.0003) and 0.34 +/- 1.59% (P = 0.02) for cortical thickness).
      Regions with percent differences greater than 5% between pump conditions were
      those close to tissue-air interfaces: entorhinal, frontal pole, parsorbitalis,
      temporal pole, and medial orbitofrontal. Synthetically adding Gaussian noise to
      the without pump MP-RAGE images yielded similar, significant detriments to
      cortical morphometry compared to without the pump. CONCLUSIONS: This study
      provides evidence that the use of PET blood sampling pumps may generate
      unstructured, Gaussian-distributed noise in MP-RAGE images that significantly
      alters the accuracy of Freesurfer-derived volume and cortical thickness
      estimates. While many cortical regions showed a percent difference of less than
      1% with the pump, regions close to tissue-air interfaces, subject to larger
      susceptibility artifacts, were significantly affected. This potential for
      decreased accuracy should be considered in PET/MR research studies utilizing
      blood sampling pumps, as well as any MRI study utilizing radiofrequency noise
      producing devices such as functional MRI task equipment and physiologic
      monitoring devices.

PMID- 29210076
TI  - In vitro effect of antiretroviral drugs on cultured primary astrocytes: analysis
      of neurotoxicity and matrix metalloproteinase inhibition.
AB  - There is little information available on the possible toxic effects that
      antiretroviral (ARV) drugs used for the treatment of human immunodeficiency virus
      (HIV)-infected subjects, may have on the central nervous system (CNS) resident
      cells. Moreover, it remains unclear whether the efficacy of the ARV drugs may
      also be due to their ability to exert extravirological effects on factors
      responsible for the development of HIV brain injury, e.g., matrix
      metalloproteinases (MMPs). This study investigates the toxicity of three
      different ARV drugs and on their ability to modulate levels and expression of
      gelatinases A (MMP-2) and B (MMP-9) in astrocytes. Primary cultures of rat
      astrocytes were activated by exposure to lipopolysaccaride (LPS) and
      simultaneously treated with darunavir, maraviroc, or raltegravir, used alone or
      in combination. Among the tested drugs, maraviroc was the less toxic for
      astrocytes. At toxic concentration (TC50 ), the studied drugs induced the
      production of reactive oxygen species (ROS), suggesting that the oxidative stress
      may represent a mechanism of ARV toxicity. As assessed by gelatin zymography and
      RT-PCR, the single antiretroviral drugs reduced levels and expression of both MMP
      2 and MMP-9 through the inhibition of the signaling transduction pathway of
      extracellular signal-regulated kinase1/2, which is involved in the regulation of
      MMP-9 gene. A synergistic inhibition of MMP-2 and MMP-9 was observed with
      combinations of the studied ARV drugs. The present results indicate that
      maraviroc, darunavir, and raltegravir, through their ability to inhibit MMP-2 and
      MMP-9 at doses non-toxic for astrocytes, might have a great potential for the
      management of HIV-associated neurological complications.

PMID- 29210077
TI  - Estimating verbal fluency and naming ability from the test of premorbid
      functioning and demographic variables: Regression equations derived from a
      regional UK sample.
AB  - OBJECTIVES: Neuropsychological assessment requires accurate estimation of an
      individual's premorbid cognitive abilities. Oral word reading tests, such as the
      test of premorbid functioning (TOPF), and demographic variables, such as age,
      sex, and level of education, provide a reasonable indication of premorbid
      intelligence, but their ability to predict other related cognitive abilities is
      less well understood. This study aimed to develop regression equations, based on
      the TOPF and demographic variables, to predict scores on tests of verbal fluency
      and naming ability. METHODS: A sample of 119 healthy adults provided demographic
      information and were tested using the TOPF, FAS, animal naming test (ANT), and
      graded naming test (GNT). Multiple regression analyses, using the TOPF and
      demographics as predictor variables, were used to estimate verbal fluency and
      naming ability test scores. Change scores and cases of significant impairment
      were calculated for two clinical samples with diagnosed neurological conditions
      (TBI and meningioma) using the method in Knight, McMahon, Green, and Skeaff ().
      RESULTS: Demographic variables provided a significant contribution to the
      prediction of all verbal fluency and naming ability test scores; however, adding
      TOPF score to the equation considerably improved prediction beyond that afforded
      by demographic variables alone. The percentage of variance accounted for by
      demographic variables and/or TOPF score varied from 19 per cent (FAS), 28 per
      cent (ANT), and 41 per cent (GNT). Change scores revealed significant differences
      in performance in the clinical groups, particularity the TBI group. CONCLUSIONS:
      Demographic variables, particularly education level, and scores on the TOPF
      should be taken into consideration when interpreting performance on tests of
      verbal fluency and naming ability.

PMID- 29210078
TI  - MdATG18a overexpression improves tolerance to nitrogen deficiency and regulates
      anthocyanin accumulation through increased autophagy in transgenic apple.
AB  - Nitrogen (N) availability is an essential factor for plant growth. Recycling and
      remobilization of N have strong impacts on crop yield and quality under N
      deficiency. Autophagy is a critical nutrient-recycling process that facilitates
      remobilization under starvation. We previously showed that an important AuTophaGy
      (ATG) protein from apple, MdATG18a, has a positive role in drought tolerance. In
      this study, we explored its biological role in response to low-N. Overexpression
      of MdATG18a in both Arabidopsis and apple improved tolerance to N-depletion and
      caused a greater accumulation of anthocyanin. The increased anthocyanin
      concentration in transgenic apple was possibly due to up-regulating flavonoid
      biosynthetic and regulatory genes (MdCHI, MdCHS, MdANS, MdPAL, MdUFGT, and
      MdMYB1) and higher soluble sugars concentration. MdATG18a overexpression enhanced
      starch degradation with up-regulating amylase gene (MdAM1) and up-regulated sugar
      metabolism related genes (MdSS1, MdHXKs, MdFK1, and MdNINVs). Furthermore,
      MdATG18a functioned in nitrate uptake and assimilation by up-regulating nitrate
      reductase MdNIA2 and 3 high-affinity nitrate transporters MdNRT2.1/2.4/2.5.
      MdATG18a overexpression also elevated other important MdATG genes expression and
      autophagosomes formation under N-depletion, which play key contributions to above
      changes. Together, these results demonstrate that overexpression of MdATG18a
      enhances tolerance to N-deficiencies and plays positive roles in anthocyanin
      biosynthesis through greater autophagic activity.

PMID- 29210079
TI  - Plasticity in activity and latency to explore differs between juvenile Atlantic
      cod Gadus morhua across a temperature gradient.
AB  - In the current study activity and latency to explore, as well as the correlation
      of these traits, were examined in individually marked juvenile Gadus morhua at 7,
      10 and 13 degrees  C. It was concluded that individual rank order of both traits
      was maintained across temperature but that the level of change differed between
      individuals.

PMID- 29210080
TI  - The Permian reptile Opisthodontosaurus carrolli: a model for acrodont tooth
      replacement and dental ontogeny.
AB  - Continuous tooth replacement is common for tetrapods, but some groups of acrodont
      lepidosaurs have lost the ability to replace their dentition (monophyodonty).
      Acrodonty, where the tooth attaches to the apex of the jawbone, is an unusual
      form of tooth attachment that has been associated with the highly autapomorphic
      condition of monophyodonty. Beyond Lepidosauria, very little is known about the
      relationship between acrodonty and monophyodonty in other amniotes. We test for
      this association with a detailed study of the dentition of Opisthodontosaurus, an
      unusual Early Permian captorhinid eureptile with acrodont dentition. We provide
      clear evidence, both histological and morphological, that there were regular
      tooth replacement events in the lower jaw of Opisthodontosaurus, similar to its
      captorhinid relatives. Thus, our study of the oldest known amniote with an
      acrodont dentition shows that acrodonty does not inhibit tooth replacement, and
      that many of the characteristics assigned to lepidosaurian acrodonty are actually
      highly derived features of lepidosaurs that have resulted secondarily from a lack
      of tooth replacement. In the context of reptilian dental evolution, we propose
      the retention of the simple definition of acrodonty, which only pertains to the
      relative position of the tooth at the apex of the jaw, where the jaw possesses
      equal lingual and labial walls. This definition of implantation therefore focuses
      solely on the spatial relationship between the tooth and the jawbone, and
      separates this relationship from tooth development and replacement.

PMID- 29210081
TI  - Improvement of monoclonal antibody-immobilized granulocyte antigen assay for the
      detection of anti-HNA-1 alloantibodies.
AB  - BACKGROUND: Currently, the gold standard for the identification of antibodies
      against human neutrophil antigens (HNAs) is the monoclonal antibody-immobilized
      granulocyte antigen (MAIGA) assay. However, the handling of this assay is
      laborious and therefore cumbersome for the rapid screening of neutrophil
      antibodies. STUDY DESIGN AND METHODS: In this study, we simplified the
      performance of the conventional MAIGA procedure and approved it for the
      identification of anti-HNA-1 with HNA-1-typed neutrophils and stable transfected
      (HEK293) cell line expressing HNA-1a, -1b, and -1c. RESULTS: In contrast to the
      conventional MAIGA, all working steps including the incubation of antibodies with
      cells, washings, cell lysis, and subsequent antibody detection could be performed
      on microtiter plates. This modification accelerates the work schedule of MAIGA
      and reduces pipetting errors. Comparison between both assay performances using
      neutrophils as target showed concordant results. Subsequently, stable mammalian
      cell lines were tested. In comparison to neutrophils, cell lines were stable for
      a longer period of time (>4 weeks) and results obtained with these cell lines
      showed better interassay precision. Analysis of different FcgammaRIIIb capture
      monoclonal antibodies (MoAbs) for the MAIGA assay showed that MoAb LNK16 is
      superior for the detection of anti-HNA-1a, -1b, and -1c, whereas MoAb 3G8 showed
      false-negative results, caused by competitive inhibition of anti-HNA-1c
      alloantibodies. CONCLUSION: The modification of MAIGA and the use of transfected
      HEK293 cells improve the detection of anti-HNA-1 alloantibodies that may allow
      screening analysis in large cohort of samples.

PMID- 29210082
TI  - Award for distinguished contributions to psychophysiology: Bruce N. Cuthbert.

PMID- 29210083
TI  - A novel association between high red blood cell alloimmunization rates and
      hereditary hemorrhagic telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant
      disorder associated with multiple arteriovenous malformations. HHT patients may
      require red blood cell (RBC) transfusion due to spontaneous hemorrhage or
      surgical bleeding. Because HHT-associated hemorrhage often occurs in submucosa we
      hypothesized that RBC alloimmunization rates in HHT patients may be higher than
      those observed in other transfused patients and investigated this in a
      retrospective study. STUDY DESIGN AND METHODS: Eighty-five patients with HHT who
      were transfused at our tertiary care facility were identified. A group of
      randomly selected, chronically transfused patients without HHT were used as
      controls (n = 207). RBC transfusion and alloantibody data were extracted from
      medical records. RESULTS: Alloimmunization rates among patients with HHT were
      significantly higher than those of controls (15.29% vs. 2.42%; p < 0.001), while
      HHT patients received fewer RBC transfusions at our institution compared to
      controls (4.27 units vs. 8.84 units; p < 0.0001). Anti-E, -K, and -c were the
      three most common alloantibodies identified in HHT patients. There was a trend
      for HHT patients to make more antibodies per alloimmunized patient than controls
      (2.38 alloantibodies vs. 1.60 alloantibodies), although this difference was not
      significant (p = 0.37). CONCLUSION: To our knowledge, this is the first study to
      evaluate RBC alloimmunization rates in patients with HHT. It is unclear whether
      the high alloimmunization rates observed are due to lifetime transfusion burden,
      underlying disease pathophysiology, or other variables. Additional studies are
      needed to evaluate the generalizability of our findings to other HHT populations
      and to consider the utility of prophylactic antigen matching for C/E/K.

PMID- 29210084
TI  - Comparison of sonography and MRI in the evaluation of stability of capitellar
      osteochondritis dissecans.
AB  - PURPOSE: To compare the diagnostic accuracies of ultrasonography (US) and
      magnetic resonance imaging (MRI) with intraoperative capitellar osteochondritis
      dissecans (COCD) fragment stability findings. METHODS: Patients whose
      International Cartilage Repair Society (ICRS) osteochondritis dissecans (OCD)
      classifications were I/II (stable) or III (unstable) were included. Patients
      underwent preoperative US and MRI. On US, lesions were evaluated as unstable when
      irregular contours of the chondral surface were observed. On MRI, lesions were
      evaluated as unstable when articular bone irregularity, a T2 high signal
      intensity interface, or a high signal intensity line through the articular
      cartilage was observed. Using the surgical assessment as the gold standard,
      accuracies of fragment stability diagnoses were calculated for US and MRI.
      RESULTS: Thirty-four patients with OCD classifications of I/II (stable) or III
      (unstable) were included. Twenty-four patients (stable: 12, unstable: 12)
      underwent preoperative US; 22 (stable: 11, unstable: 11) underwent preoperative
      MRI. Preoperative US and MRI stability assessments correctly matched
      intraoperative fragment findings in 23 of 24 patients and 16 of 22 patients,
      respectively. US criteria in this study achieved superior accuracy compared with
      MRI criteria (96% vs. 73%; P < .05). CONCLUSION: US was a useful tool for
      evaluating fragment instability in COCD.

PMID- 29210085
TI  - Subclinical systolic and diastolic dysfunctions in patients with metabolic
      syndrome and angiographically normal coronary arteries: An echocardiographic
      study.
AB  - BACKGROUND: The metabolic syndrome (MetS), as a combination of cardiovascular
      risk factors, is associated with subclinical cardiovascular diseases. We sought
      to evaluate the subclinical myocardial dysfunctions using echocardiography in
      patients with normal coronary arteries. MATERIALS AND METHODS: In this cross
      sectional study, we assessed 50 consecutive patients with angiographically-proven
      normal coronary arteries and a left ventricular (LV) ejection fraction (EF)
      >=55%. The diagnosis of MetS was based on the National Cholesterol Education
      Program/Adult Treatment Panel III criteria. All patients were examined using
      conventional and two-dimensional speckle tracking echocardiography for evaluating
      the myocardial functions. RESULTS: The patients' mean age was 52.3 +/- 8.3 years
      with 32 females (64%). LV EF, mass index, and full volume were comparable between
      groups. The LV myocardial performance index (0.40 +/- 0.13 vs. 0.32 +/- 0.10; P =
      .027), global longitudinal strain (GLS, -15.8 +/- 4.5 vs. -19.7 +/- 2.1; P <
      .001), and global circumferential strain (-17.9 +/- 6.1 vs. -21.5 +/- 3.3; P =
      .014) were different between patients with or without MetS, respectively. The GLS
      discriminated patients with MetS (area under the curve = 0.837, sensitivity 80%,
      specificity 88%, P < .001). CONCLUSIONS: In MetS without coronary artery disease,
      echocardiography demonstrated subclinical systolic and diastolic dysfunction.

PMID- 29210086
TI  - Evolution Is Linear: Debunking Life's Little Joke.
AB  - Linear depictions of the evolutionary process are ubiquitous in popular culture,
      but linear evolutionary imagery is strongly rejected by scientists who argue that
      evolution branches. This point is frequently illustrated by saying that we didn't
      evolve from monkeys, but that we are related to them as collateral relatives.
      Yet, we did evolve from monkeys, but our monkey ancestors are extinct, not
      extant. Influential voices, such as the late Stephen Jay Gould, have misled
      audiences for decades by falsely portraying the linear and branching aspects of
      evolution to be in conflict, and by failing to distinguish between the legitimate
      linearity of evolutionary descent, and the branching relationships among
      collateral relatives that result when lineages of ancestors diverge. The purpose
      of this article is to correct the widespread misplaced rejection of linear
      evolutionary imagery, and to re-emphasize the basic truth that the evolutionary
      process is fundamentally linear.

PMID- 29210087
TI  - Methotrexate use in allergic contact dermatitis: a retrospective study.
AB  - BACKGROUND: Methotrexate, a folate antimetabolite, is used to treat atopic
      dermatitis and psoriasis. Although methotrexate's therapeutic efficacy has been
      noted in the literature, there are few data on the efficacy of methotrexate
      treatment for allergic contact dermatitis. OBJECTIVE: To evaluate the efficacy
      and tolerability of methotrexate in treating allergic contact dermatitis at a
      single institution, and also to assess methotrexate efficacy in patients with
      chronic, unavoidable allergen exposure. METHODS: We performed a retrospective
      chart review of 32 patients diagnosed with allergic contact dermatitis by
      positive patch test reactions, and who received treatment with methotrexate from
      November 2010 to November 2014. Demographic and treatment-associated data were
      collected from electronic medical records. Ten patients were identified as
      allergen non-avoiders secondary to their occupation, and were subgrouped as such.
      RESULTS: Seventy-eight per cent (25/32) of patients showed either a partial or a
      complete response. Methotrexate had a comparable efficacy rate in the allergen
      non-avoiders subset, at 10 of 10. Of the 32 patients, 23% (5/22) had complete
      clearance of their dermatitis, and 1/10 of allergen non-avoiders had complete
      clearance of their dermatitis. CONCLUSION: Methotrexate is a well-tolerated and
      effective treatment for allergic contact dermatitis, and shows comparable
      efficacy to immunomodulatory agents such as cyclosporine and azathioprine, with
      robust efficacy despite persistent allergen exposure in patients with allergic
      contact dermatitis.

PMID- 29210089
TI  - Aicardi-Goutieres syndrome with muscle involvement in early infancy.

PMID- 29210088
TI  - Exodermis and endodermis are the sites of xanthone biosynthesis in Hypericum
      perforatum roots.
AB  - Xanthones are specialized metabolites with antimicrobial properties, which
      accumulate in roots of Hypericum perforatum. This medicinal plant provides widely
      taken remedies for depressive episodes and skin disorders. Owing to the array of
      pharmacological activities, xanthone derivatives attract attention for drug
      design. Little is known about the sites of biosynthesis and accumulation of
      xanthones in roots. Xanthone biosynthesis is localized at the transcript,
      protein, and product levels using in situ mRNA hybridization, indirect
      immunofluorescence detection, and high lateral and mass resolution mass
      spectrometry imaging (AP-SMALDI-FT-Orbitrap MSI), respectively. The carbon
      skeleton of xanthones is formed by benzophenone synthase (BPS), for which a cDNA
      was cloned from root cultures of H. perforatum var. angustifolium. Both the BPS
      protein and the BPS transcripts are localized to the exodermis and the endodermis
      of roots. The xanthone compounds as the BPS products are detected in the same
      tissues. The exodermis and the endodermis, which are the outermost and innermost
      cell layers of the root cortex, respectively, are not only highly specialized
      barriers for controlling the passage of water and solutes but also preformed
      lines of defence against soilborne pathogens and predators.

PMID- 29210090
TI  - Towards understanding the dose and timing effect of hydrocortisone treatment on
      the scleral ossicle system within the chicken eye.
AB  - Previous work, almost four decades ago, showed that hydrocortisone (HC) treatment
      reduces the number of skeletogenic condensations that give rise to the scleral
      ossicles in the chicken eye. The scleral ossicles are a ring of overlapping
      intramembranous bones, the sclerotic ring, and are present in most reptiles,
      including birds. The scleral condensations that give rise to the scleral ossicles
      are induced by a series of overlying thickenings (or papillae) of the
      conjunctival epithelium. Here, we further explore the effects of altering the
      dosage and timing of HC treatment on the morphology and number of skeletogenic
      condensations and conjunctival papillae. We show that high doses can completely
      obliterate the entire sclerotic ring. Significantly, the reduction in papillae
      number we observed was less extreme than that of the scleral condensations,
      indicating that additional factors contribute to the observed skeletogenic
      condensation loss. Via immunohistochemical analyses, we show that HC treatment
      alters the spatial expression pattern of several extracellular matrix components
      (tenascin-C, decorin and procollagen I) and also alters the vasculature network
      within the sclera. This research provides important insights into understanding
      the role of the scleral tissue components in ossicle development within the
      vertebrate eye.

PMID- 29210091
TI  - Clinical relevance of radiographic linear branching mineral opacities in the
      canine liver.
AB  - OBJECTIVES: To assess the prevalence, clinical significance and breed
      distribution of linear branching mineralisation superimposed on the hepatic
      radiographic silhouette in dogs. MATERIALS AND METHODS: Retrospective review of
      radiographs or ultrasound images of dogs showing branching mineralisation in the
      liver. RESULTS: Over the 30-year review period, 17 cases were identified and the
      mineralisation had a predominantly ventral distribution. Seven of the 17 were
      cavalier King Charles spaniels, and four of the total 17 dogs were diagnosed with
      hepatobiliary system disease. Five dogs had repeat radiographs, of which four
      showed no change in the pattern and one developed the pattern 6 years after being
      diagnosed with cholangiohepatitis. Serum calcium concentrations were normal in
      all patients. Liver enzymes were markedly elevated only in the dog diagnosed with
      cholangiohepatitis. Histology performed on three patients showed no convincing
      evidence of primary liver disease. CLINICAL SIGNIFICANCE: Branching
      mineralisation in the liver parenchyma is a rare finding in dogs with little or
      no clinical significance and cavalier King Charles spaniels may be predisposed.
      Biopsy of the liver of affected dogs with no clinical or clinicopathological
      evidence of liver disease is unlikely to be helpful in these cases.

PMID- 29210092
TI  - Comparison of digital and film chest radiography for detection and medical
      surveillance of silicosis in a setting with a high burden of tuberculosis.
AB  - BACKGROUND: Continuing use of analog film and digital chest radiography for
      screening and surveillance for pneumoconiosis and tuberculosis in lower and
      middle income countries raises questions of equivalence of disease detection.
      This study compared analog to digital images for intra-rater agreement across
      formats and prevalence of changes related to silicosis and tuberculosis among
      South African gold miners using the International Labour Organization
      classification system. METHODS: Miners with diverse radiological presentations of
      silicosis and tuberculosis were recruited. Digital and film chest images on each
      subject were classified by four expert readers. RESULTS: Readings of film and
      soft copy digital images showed no significant differences in prevalence of
      tuberculosis or silicosis, and intra-rater agreement across formats was fair to
      good. Hard copy images yielded higher prevalences. CONCLUSION: Film and digital
      soft copy images show consistent prevalence of findings, and generally fair to
      good intra-rater agreement for findings related to silicosis and tuberculosis.

PMID- 29210094
TI  - Infliximab trough concentrations during maintenance therapy are associated with
      endoscopic and histologic healing in ulcerative colitis.
AB  - BACKGROUND: Endoscopic and histologic healing are emerging as new therapeutic
      goals in ulcerative colitis (UC), as these endpoints are associated with less
      relapse, hospitalization and colectomy. AIM: To investigate the association of
      serum infliximab trough concentrations during maintenance therapy with endoscopic
      or histologic healing in UC. METHODS: In this multi-center retrospective cohort
      study, we included consecutive patients with moderate-to-severe UC on infliximab
      maintenance therapy who had an endoscopic evaluation and underwent therapeutic
      drug monitoring within three months of the colonoscopy, between February 2008 and
      March 2016. Per event analysis was performed. Endoscopic healing was defined as
      Mayo endoscopic sub-score of <=1. Histologic healing was defined as no or only
      focal mild active inflammation. RESULTS: Seventy colonoscopies from 56 patients
      were evaluated. Infliximab trough concentrations (median [interquartile range])
      were significantly higher in patients with endoscopic (11.3 [7.6-14.5] vs 6.3 [0
      9.8] MUg/mL, P < .001) or histologic (11.1 [6.7-14.5] vs 6.7 [0-9.9] MUg/mL, P =
      .002) healing, respectively, compared to patients without healing. Receiver
      operating characteristic analyses identified infliximab trough concentration
      thresholds of 7.5 (area under the curve [AUC]: 0.758) and 10.5 (AUC: 0.721)
      MUg/mL to be associated with endoscopic and histologic healing, respectively.
      Multiple logistic regression analysis identified infliximab trough concentration
      >=7.5 (P = .013; odds ratio [OR]: 4.3; 95% confidence intervals [CI]: 1.4-13.3)
      and >=10.5 MUg/mL (P = .013; OR: 3.8; 95% CI: 1.3-11) as independent factors
      associated with endoscopic and histologic healing, respectively. CONCLUSIONS:
      This study demonstrated that infliximab trough concentrations during maintenance
      therapy are associated with endoscopic and histologic healing in patients with
      UC.

PMID- 29210095
TI  - Hereditary xerocytosis: Diagnostic considerations.

PMID- 29210096
TI  - Obesity and type 2 diabetes are important risk factors underlying previously
      undiagnosed cirrhosis in general practice: a cross-sectional study using
      transient elastography.
AB  - BACKGROUND: Rising cirrhosis incidence and mortality in the United Kingdom has
      been attributed predominantly to excess alcohol consumption. However, metabolic
      risk factors such as Type 2 diabetes and obesity may also be important. AIM: To
      screen at-risk individuals in general practice for undetected cirrhosis using
      transient elastography and study the risk factors underlying these cases.
      METHODS: The study was undertaken in 4 general practices (adult patient
      population 20 868) between February 2012 and September 2014. Patients with
      defined risk factors for chronic liver disease (hazardous alcohol use and/or Type
      2 diabetes) were identified from the General Practice electronic records and
      invited for transient elastography. Elevated liver stiffness was defined as >=8
      kPa. Cirrhosis was confirmed by established histological, radiological and
      biochemical methods. RESULTS: Two thousand three hundred and sixty eight patients
      were invited for transient elastography and 899/919 who attended (97.8%) had
      valid measurements. Of these 230 patients had elevated liver stiffness (25.6%)
      and 27 had cirrhosis (2.9%). Risk factors for new cirrhosis diagnoses were
      obesity and/or Type 2 diabetes in 16 patients (59.3%), alcohol alone in 3 (11.1%)
      and both alcohol and obesity and/or diabetes in eight (29.6%). Presence of
      cirrhosis was significantly increased in obese patients with Type 2 diabetes or
      hazardous alcohol use compared to non-obese (odds ratio 9.4 [95% CI 2.2-40.9] and
      5.6 [95% CI 1.6-19.7] respectively). CONCLUSIONS: The number of new cases of
      cirrhosis diagnosed clearly demonstrates that existing estimates of prevalence
      are likely to be gross underestimates. Obesity was an important risk factor for
      cirrhosis within both alcohol users and diabetics.

PMID- 29210097
TI  - Radiography of the distal extremity of the manus in the donkey foal: Normal
      images and quantitative characterization from birth to 2 years of age: A pilot
      study.
AB  - This study describes a radiographic survey of the anatomical development of the
      distal extremity of the manus in the donkey from 0 to 2 years of age. The right
      distal limb of 10 donkey foals, born in the spring of 2012, underwent radiographs
      every month for the first 6 months of age and every 3 months during the following
      18 months. Latero-medial radiographs with and without barium marker at the
      coronary band and dorso-palmar radiographs with both front feet in weight bearing
      were obtained. The distal physis of the third metacarpal bone and the proximal
      physis of the proximal phalanx (phalanx proximalis) were closed at the mean age
      of 18.6 months. The distal physis of the proximal phalanx appeared as a clear
      radiolucent line at 2 weeks of age and was still subtly visible in some donkeys
      at 24 months. The proximal physis of the middle phalanx (phalanx media) was
      closed at the mean age of 16.7 months. The distal physis of this phalanx was
      visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was
      triangular at birth. At the age of 20-21 months, the palmar processes (processus
      palmares) were both developed. The navicular bone (os sesamoideum distalis) was
      developed at the mean age of 9 months. The proximal sesamoid bones (ossa
      sesamoidea proximalia) were seen in continuously development during the 24
      months. It seems that the physes in the distal extremity of the manus in the
      donkey close at an older age than the physes in the horse.

PMID- 29210098
TI  - Regional gastrointestinal contractility parameters using the wireless motility
      capsule: inter-observer reproducibility and influence of age, gender and study
      country.
AB  - BACKGROUND: The wireless motility capsule concurrently measures temperature, pH
      and pressure as it traverses the gastrointestinal tract. AIMS: To describe
      normative values for motility/contractility parameters across age, gender and
      testing centres. METHODS: Healthy participants underwent a standardised wireless
      motility capsule assessment following an overnight fast and consumption of a meal
      of known nutritional content. Traces were divided into regions of interest and
      analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter
      observer agreement was independently assessed by 2 investigators. RESULTS:
      Normative data for motility/contractility parameters (maximum amplitude, mean
      peak amplitude, contraction frequency and motility index) are presented for 107
      individuals (62 male, median age 40 years, range 18-78). MotiliGI-Gastric, small
      bowel and colonic maximal contraction amplitude correlated with age (r = .24, P =
      .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility
      index was higher in females than males (150.4 +/- 12 vs 122 +/- 7.6, P = .04).
      Inter-observer agreement was excellent for transit times, pH and
      contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and
      colonic loge motility index correlated with the respective area under the
      contraction curve, total contractions, sum of amplitudes and contraction
      frequency (all r>.35, P < .0003) but not with transit times. CONCLUSIONS: Our
      analysis provides normative data for motility/contractility parameters. Log
      motility index summarises a number of measures. In future, the measurement of
      contractile activity with the wireless motility capsule may potentially aid in
      the diagnosis of disease states such as visceral myopathic disorders.

PMID- 29210099
TI  - Behavioral and hormonal responses to the availability of forage material in
      Western lowland gorillas (Gorilla gorilla gorilla).
AB  - We investigated how forage material affects indicators of welfare in three male
      Western lowland gorillas (Gorilla gorilla gorilla) at the Detroit Zoo. In
      addition to their maintenance diet and enrichment foods, the gorillas generally
      received forage material four times a week. From this baseline, we systematically
      manipulated how much forage material the group received on a weekly basis, with
      either daily or bi (twice)-weekly presentation of browse (mulberry, Morus sp.) or
      alfalfa hay. We collected behavioral data (60 hr per gorilla) and measured fecal
      glucocorticoid metabolites (FGM). Mixed models indicated that the presence of
      forage material significantly increased time feeding (F2,351  = 9.58, p < 0.001),
      and decreased rates of noncontact aggression (F2,351  = 3.69, p = 0.03), and
      regurgitation and reingestion (F2,353  = 4.70, p = 0.01). Regurgitation and
      reingestion were never observed during the condition when forage material was
      provided daily. When forage material was provided, time spent feeding was similar
      across gorillas, compared to a disproportionately greater amount of time spent
      feeding by the dominant individual when forage material was absent. Providing
      forage material in addition to the regular diet likely created more opportunities
      for equitable feeding for the subordinate gorillas. FGM concentrations did not
      vary based on the presence or type of forage material available and, instead,
      likely reflected group social dynamics. In general, alfalfa and mulberry had
      similar impacts on behavior, indicating that alfalfa can be an adequate
      behavioral substitute during times when browse is less readily available for
      gorillas housed in seasonally variable climates.

PMID- 29210100
TI  - Morphological fine tuning of the feeding apparatus to proboscis length in
      Hesperiidae (Lepidoptera).
AB  - The form and function of the hesperiid feeding apparatus was studied in detail.
      The butterflies in the family Hesperiidae are of particular interest because the
      longest proboscis ever recorded in Papilionoidea was found in the Neotropical
      genus Damas. We focused on the functional morphology by comparing proboscis
      morphology as well as size and composition of both the stipes pump and the
      cibarial suction pump in skippers with short and extremely long proboscis.
      Results revealed that all studied Hesperiidae have the same proboscis
      micromorphology and sensilla endowment regardless of the proboscis length.
      However, the numbers of internal muscles of the proboscis, the morphology of the
      stipes pump as well as the pumping organs for nectar uptake are related to the
      proboscis length. We conclude that the low number of tip sensilla compared to
      proboscis length is responsible for remarkably longer manipulation times of long
      proboscid species during flower visits. The organs for proboscis movements and
      nectar uptake organs are well tuned to the respective proboscis length and are
      accordingly bigger in species with a proboscis that measures twice the body
      length.

PMID- 29210101
TI  - Problems of dual vulnerability in nutrition: A qualitative study of older persons
      caring for under 5-year-olds in post-disaster Haiti.
AB  - SITUATION: Malnutrition plays a significant role in under-five mortality rates
      following disasters. Older people play an important role in childcare in non
      Western societies, which often increases in displacement contexts. Until now,
      policy, in general, and nutrition programmes, in particular, have focused on the
      mother-child dyad. AIM: To gather information on possible barriers to older
      carers accessing nutritional services for the children they care for and explore
      ways to overcome these obstacles. METHOD: A qualitative approach was taken to
      explore the experiences of the carers themselves. Focus group discussions
      provided data, which were analysed using grounded theory. RESULTS: Data collected
      showed older people have similar needs to other caregivers in emergency settings,
      needs that are often amplified by age. Moreover, many barriers to accessing
      services were elicited, including targeting and advertising of nutritional
      programmes, alongside physical and psychosocial barriers to assessing existing
      support. Participants generated potential solutions to each identified barrier.
      CONCLUSION: As older people in Haiti were often the sole carers of under-fives,
      there is a need to recognise their importance in this role and support them
      within. More generally, in any emergency setting, organisations need take into
      account all stakeholders in child nutrition when planning and implementing
      programmes.

PMID- 29210102
TI  - The use of droplet digital PCR in liquid biopsies: A highly sensitive technique
      for MYD88 p.(L265P) detection in cerebrospinal fluid.
AB  - The gold standard for diagnosis of central nervous system lymphomas still regards
      a stereotactic brain biopsy, with the risk of major complications for the
      patient. As tumor cells can be detected in cerebrospinal fluid (CSF), CSF
      analysis can be used as an alternative. In this respect, mutation analysis in CSF
      can be of added value to other diagnostic parameters such a cytomorphology and
      clonality analysis. A well-known example of targeted mutation analysis entails
      MYD88 p.(L265P) detection, which is present in the majority of Bing Neel syndrome
      and primary central nervous system lymphoma (PCNSL) patients. Unfortunately,
      tumor yield in CSF can be very low. Therefore, use of the highly sensitive
      droplet digital PCR (ddPCR) might be a suitable analysis strategy for targeted
      mutation detection. We analyzed 26 formalin fixed paraffin embedded (FFPE)
      samples (8 positive and 18 negative for MYD88 p.(L265P) mutation) by ddPCR, of
      which the results were compared with next generation sequencing (NGS).
      Subsequently, 32 CSF samples were analyzed by ddPCR. ddPCR and NGS results on
      FFPE material showed 100% concordance. Among the 32 CSF samples, 9 belonged to
      patients with lymphoplasmacytic lymphoma (LPL) and clinical suspicion of Bing
      Neel syndrome, and 3 belonged to patients with PCNSL. Nine of these samples
      tested positive for MYD88 p.(L265P) (8 LPL and 1 PCNSL). This study shows that
      sensitive MYD88 mutation analysis by ddPCR in CSF is highly reliable and can be
      applied even when DNA input is low. Therefore, ddPCR is of added value to current
      diagnostic parameters, especially when the available amount of DNA is limited.

PMID- 29210104
TI  - Threshold responses of Amazonian stream fishes to timing and extent of
      deforestation.
AB  - Deforestation is a primary driver of biodiversity change through habitat loss and
      fragmentation. Stream biodiversity may not respond to deforestation in a simple
      linear relationship. Rather, threshold responses to extent and timing of
      deforestation may occur. Identification of critical deforestation thresholds is
      needed for effective conservation and management. We tested for threshold
      responses of fish species and functional groups to degree of watershed and
      riparian zone deforestation and time since impact in 75 streams in the western
      Brazilian Amazon. We used remote sensing to assess deforestation from 1984 to
      2011. Fish assemblages were sampled with seines and dip nets in a standardized
      manner. Fish species (n = 84) were classified into 20 functional groups based on
      ecomorphological traits associated with habitat use, feeding, and locomotion.
      Threshold responses were quantified using threshold indicator taxa analysis.
      Negative threshold responses to deforestation were common and consistently
      occurred at very low levels of deforestation (<20%) and soon after impact (<10
      years). Sensitive species were functionally unique and associated with complex
      habitats and structures of allochthonous origin found in forested watersheds.
      Positive threshold responses of species were less common and generally occurred
      at >70% deforestation and >10 years after impact. Findings were similar at the
      community level for both taxonomic and functional analyses. Because most negative
      threshold responses occurred at low levels of deforestation and soon after
      impact, even minimal change is expected to negatively affect biodiversity.
      Delayed positive threshold responses to extreme deforestation by a few species do
      not offset the loss of sensitive taxa and likely contribute to biotic
      homogenization.

PMID- 29210103
TI  - Myelination and mTOR.
AB  - Myelinating cells surround axons to accelerate the propagation of action
      potentials, to support axonal health, and to refine neural circuits. Myelination
      is metabolically demanding and, consistent with this notion, mTORC1-a signaling
      hub coordinating cell metabolism-has been implicated as a key signal for
      myelination. Here, we will discuss metabolic aspects of myelination, illustrate
      the main metabolic processes regulated by mTORC1, and review advances on the role
      of mTORC1 in myelination of the central nervous system and the peripheral nervous
      system. Recent progress has revealed a complex role of mTORC1 in myelinating
      cells that includes, besides positive regulation of myelin growth, additional
      critical functions in the stages preceding active myelination. Based on the
      available evidence, we will also highlight potential nonoverlapping roles between
      mTORC1 and its known main upstream pathways PI3K-Akt, Mek-Erk1/2, and AMPK in
      myelinating cells. Finally, we will discuss signals that are already known or
      hypothesized to be responsible for the regulation of mTORC1 activity in
      myelinating cells.

PMID- 29210105
TI  - Systematic Review and Meta-Analysis of Diagnostic Accuracy of Serum Refractometry
      and Brix Refractometry for the Diagnosis of Inadequate Transfer of Passive
      Immunity in Calves.
AB  - BACKGROUND: Transfer of passive immunity in calves can be assessed by direct
      measurement of immunoglobulin G (IgG) by methods such as radial immunodiffusion
      (RID) or turbidimetric immunoassay (TIA). IgG can also be measured indirectly by
      methods such as serum refractometry (REF) or Brix refractometry (BRIX).
      OBJECTIVES: To determine the accuracy of REF and BRIX for assessment of
      inadequate transfer of passive immunity (ITPI) in calves. DESIGN: Systematic
      review and meta-analysis of diagnostic accuracy studies. METHODS: Databases
      (PubMed and CAB Abstract, Searchable Proceedings of Animal Science) and Google
      Scholar were searched for relevant studies. Studies were eligible if the accuracy
      (sensitivity and specificity) of REF or BRIX was determined using direct
      measurement of IgG by RID or turbidimetry as the reference standard. The study
      population included calves <14 days old that were fed with natural colostrum
      (colostrum replacement products were excluded). Quality assessment was performed
      by the QUADAS-2 tool. Hierarchical models were used for meta-analysis. RESULTS:
      From 1,291 references identified, 13 studies of 3,788 calves were included. Of
      these, 11 studies evaluated REF and 5 studies evaluated BRIX. The median (range)
      prevalence of ITPI (defined as calves with IgG <10 g/L by RID or TIA) was 21%
      (1.3-56%). Risk of bias and applicability concerns were generally low or unclear.
      For REF, summary estimates were obtained for 2 different cutoffs: 5.2 g/dL (6
      studies) and 5.5 g/dL (5 studies). For the 5.2 g/dL cutoff, the summary
      sensitivity (95% CI) and specificity (95% CI) were 76.1% (63.8-85.2%) and 89.3%
      (82.3-93.7%), and 88.2% (80.2-93.3%) and 77.9% (74.5-81.0%) for the 5.5 g/dL
      cutoff. Due to the low number of studies using the same cutoffs, summary
      estimates could not be obtained for BRIX. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Despite their widespread use on dairy farms, evidence about the optimal strategy
      for using refractometry, including the optimal cutoff, are sparse (especially for
      BRIX). When using REF to rule out ITPI in herds, the 5.5 g/dL cutoff may be used
      whereas for ruling in ITPI, the 5.2 g/dL cutoff may be used.

PMID- 29210106
TI  - Preemptive second kidney transplantation is associated with better graft survival
      compared with non-preemptive second transplantation: a multicenter French 2000
      2014 cohort study.
AB  - The impact of preemptive second kidney transplantation (2KT) on graft and patient
      survival is poorly established. The association between preemptive 2KT (p2KT, N =
      93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314)
      recipients using propensity score methods. During the follow-up, there were 274
      returns to dialysis and 134 deaths. p2KT was associated with lower death-censored
      graft loss (HR = 0.39 [0.18-0.88], P = 0.024) and graft failure from any cause
      including death (HR = 0.42 [0.22-0.80], P = 0.008). Similar associations were
      observed for death with a functioning graft, although not reaching statistical
      significance (HR = 0.47 [0.17-1.26], P = 0.13). There was a significant
      interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT
      was not significantly associated with the risk of graft failure from any cause
      including death in living donor 2KT (P = 0.39), whereas the association was
      substantial in the deceased donor subset (HR = 0.30 [0.14-0.64], P = 0.002). Of
      note, the adjusted graft survival of p2KT with deceased donor paralleled that of
      2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and
      76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study
      analyzed using propensity scores suggests that p2KT is associated with better
      graft prognosis.

PMID- 29210107
TI  - Higher serotonin transporter availability in early-onset obsessive-compulsive
      disorder patients undergoing escitalopram treatment: A [11 C]DASB PET study.
AB  - OBJECTIVE: Early-onset obsessive-compulsive disorder (EOCD) and late-onset
      obsessive-compulsive disorder (LOCD) are distinct subtypes of obsessive
      compulsive disorder (OCD). OCD patients are treated with serotonin reuptake
      inhibitors, but the difference in serotonin transporter (SERT) availability
      between medicated EOCD and LOCD is unexplored yet. METHODS: Six EOCD and 6 LOCD
      patients were enrolled. They underwent serial [11 C]DASB positron emission
      tomography scans during maintenance therapy with escitalopram, and their plasma
      concentration of escitalopram was measured simultaneously with the scan. Then,
      the drug-free binding potential of SERT was calculated by pharmacokinetic
      pharmacodynamic modelling. RESULTS: In comparison with LOCD patients, SERT
      availability was significantly higher in the putamen of EOCD patients (U = 4, p =
      .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p =
      .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen
      showed a negative correlation (r = -.580, p = .048) with age of onset of the
      disease, but not with the Yale-Brown Obsessive Compulsive Scale scores.
      CONCLUSIONS: These findings indicate that the earlier the age of onset of OCD,
      the less serotonergic pathology there is and that this difference remains even
      after long-term serotonin reuptake inhibitor treatment. Clinically, it might
      suggest that nonserotonergic treatments would be a better option for EOCD
      patients.

PMID- 29210108
TI  - Kidney transplant outcomes from older deceased donors: a paired kidney analysis
      by the European Renal Association-European Dialysis and Transplant Association
      Registry.
AB  - As the median age of deceased kidney donors rises, updated knowledge of
      transplant outcomes from older deceased donors in differing donor-recipient age
      groups is required. Using ERA-EDTA Registry data we determined survival outcomes
      of kidney allografts donated from the same older deceased donor (55-70 years),
      and transplanted into one recipient younger and one recipient of similar age to
      the donor. The recipient pairs were divided into two groups: group 1; younger
      (median age: 52 years) and older (60 years) and group 2; younger (41 years) and
      older (60 years). A total of 1410 adults were transplanted during 2000-2007.
      Compared to the older recipients, the mean number of functioning graft years at
      10 years was 6 months longer in the group 1 and group 2 younger recipients (P <
      0.001). Ten-year graft survival was 54% and 40% for the group 1 younger and older
      recipients, and 60% and 49% for the group 2 younger and older recipients. Paired
      Cox regression analyses showed a lower risk of graft failure (group 1 younger;
      adjusted relative risk [RRa]:0.57, 95% CI:0.41-0.79, and group 2 younger;
      RRa:0.63, 95% CI:0.47-0.85) in younger recipients. Outcomes from older deceased
      donor allografts transplanted into differing donor-recipient age groups are
      better than previously reported. These allografts remain a valuable transplant
      resource, particularly for similar-aged recipients.

PMID- 29210109
TI  - Xenotransplantation: back to the future?
AB  - The field of xenotransplantation has fluctuated between great optimism and doubts
      over the last 50 years. The initial clinical attempts were extremely ambitious
      but faced technical and ethical issues that prompted the research community to go
      back to preclinical studies. Important players left the field due to perceived
      xenozoonotic risks and the lack of progress in pig-to-nonhuman-primate transplant
      models. Initial apparently unsurmountable issues appear now to be possible to
      overcome due to progress of genetic engineering, allowing the generation of
      multiple-xenoantigen knockout pigs that express human transgenes and the
      genomewide inactivation of porcine endogenous retroviruses. These important steps
      forward were made possible by new genome editing technologies, such as
      CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in
      the genome. An additional emerging perspective is the possibility of growing
      humanized organs in pigs using blastocyst complementation. This article
      summarizes the current advances in xenotransplantation research in nonhuman
      primates, and it describes the newly developed genome editing technology tools
      and interspecific organ generation.

PMID- 29210110
TI  - Paediatric breath-holding spells are associated with autonomic dysfunction and
      iron deficiency may play a role.
AB  - AIM: This study assessed cardiac performance and iron in subjects aged 12-36
      months with breath-holding spells (BHSs). METHODS: We consecutively recruited 40
      subjects (55% male) experiencing BHSs from the general paediatric outpatients
      department at the Children's Hospital, Ain Shams University, Egypt, from 2015 to
      2016. The 20 matched comparisons were mainly healthy siblings. The workup
      included iron levels and electrocardiograms. RESULTS: The age at the onset of
      BHSs was 5-24 months with a median monthly frequency of 13. Almost two-thirds of
      the patients had cyanotic spells, and one-third had pallid spells, lasting 25-90
      seconds. Lower serum iron levels and higher QT dispersion and T-wave dispersion
      were recorded in patients than the comparison group, and 4.8% had dysrhythmia and
      bradycardia. We observed higher durations of bradycardia during attacks and
      higher occurrences of dysrhythmia during cyanotic spells, which were more
      frequent in patients with prolonged or frequent BHSs. CONCLUSION: Our study of
      patients aged 12-13 months supported the theory of autonomic dysfunction in BHSs.
      The ECG findings, especially in patients with prolonged or frequent spells, need
      to be studied further to evaluate the risk of life-threatening events. Iron
      deficiency may play a role in autonomic dysfunction in patients with BHSs.

PMID- 29210112
TI  - Parents with overweight children two and five years of age did not perceive them
      as weighing too much.
AB  - AIM: This study examined whether the parents of children who were overweight at
      two and five years of age perceived their children as being too heavy and related
      the findings to sociodemographic factors. METHODS: The data collection included
      parental questionnaires and anthropometric data from a longitudinal birth cohort
      of 2666 children born in the south-west region of Sweden in 2007-2008. RESULTS:
      We found that 14.9 and 11.8% of the children were considered overweight or obese
      at the age of two and five, but 96.4 and 87.1% of their parents perceived their
      weight to be just about right at these ages. The difference was statistically
      significant (p < 0.001). Parents who were overweight themselves and had a low
      educational level were associated with a higher probability of misperception: at
      two years of age, the odds ratio was 2.75 (95% confidence interval 1.80-4.21),
      and at the age of five, it was 1.92 (1.24-2.97). CONCLUSION: Most parents did not
      perceive that their overweight children weighed too much, but their judgement
      improved as the child got older. Parents who were overweight or had a low
      educational level were more likely to misperceive their child's weight. Health
      Care professionals need to be aware of this gap in perception.

PMID- 29210111
TI  - STRO-1 confers myofibroblast transdifferentiation in fibroblasts derived from
      oral submucous fibrosis.
AB  - BACKGROUND: STRO-1 is a mesenchymal cell marker present on all clonogenic stromal
      precursors. Current evidence has indicated that the pathogenesis of fibrotic
      changes may be mediated by stemness properties. The aim of this study was to
      investigate the role of STRO-1 in areca quid chewing-associated oral submucous
      fibrosis (OSF). METHODS: Thirty OSF specimens and ten normal buccal mucosae were
      examined by immunohistochemistry. The activity of STRO-1 from fibroblasts
      cultured from normal buccal mucosa (BMFs) and OSF (OSFFs) were measureed and the
      effect of arecoline, a major areca nut alkaloid, on STRO-1 in BMFs was evaluated.
      Compared the activities between sorted STRO-1+ cells and STRO-1- cells from OSFF
      were measured by collagen gel contraction, migration, invasion abilities, and the
      expression of alpha-smooth muscle actin (alpha-SMA) and pro-alpha1 (I) chain of
      type I collagen. RESULTS: Our results first showed that the expression of STRO-1
      was more evident in areca quid chewing-associated OSF than normal buccal mucosa
      tissues (P < .05). Arecoline dose-dependently activated the level of STRO-1 in
      BMFs (P < .05). The relative expression of STRO-1 was significantly higher in
      OSFFs compared with BMFs (P < .05). In addition, the sorted STRO-1+ cells from
      OSFFs exhibited higher collagen gel contraction, migration, and invasion
      abilities as well as elevated expression of alpha-SMA and pro-alpha1 (I) chain of
      type I collagen than the negative subset (P < .05). CONCLUSION: These findings
      suggested that the stemness marker STRO-1 may be a crucial factor in the
      pathogenesis of areca quid chewing-associated OSF.

PMID- 29210113
TI  - Realizing Over 13% Efficiency in Green-Solvent-Processed Nonfullerene Organic
      Solar Cells Enabled by 1,3,4-Thiadiazole-Based Wide-Bandgap Copolymers.
AB  - Two novel wide-bandgap copolymers, PBDT-TDZ and PBDTS-TDZ, are developed based on
      1,3,4-thiadiazole (TDZ) and benzo[1,2-b:4,5-b']dithiophene (BDT) building blocks.
      These copolymers exhibit wide bandgaps over 2.07 eV and low-lying highest
      occupied molecular orbital (HOMO) levels below -5.35 eV, which match well with
      the typical low-bandgap acceptor of ITIC, resulting in a good complementary
      absorption from 300 to 900 nm and a low HOMO level offset (<=0.13 eV). Compared
      to PBDT-TDZ, PBDTS-TDZ with alkylthio side chains exhibits the stronger optical
      absorption, lower-lying HOMO level, and higher crystallinity. By using a single
      green solvent of o-xylene, PBDTS-TDZ:ITIC devices exhibit a large open-circuit
      voltage (Voc ) up to 1.10 eV and an extremely low energy loss (Eloss ) of 0.48
      eV. At the same time, the desirable high short-circuit current density (Jsc ) of
      17.78 mA cm-2 and fill factor of 65.4% are also obtained, giving rise to a high
      power conversion efficiency (PCE) of 12.80% without any additive and post
      treatment. When adopting a homotandem device architecture, the PCE is further
      improved to 13.35% (certified as 13.19%) with a much larger Voc of 2.13 V, which
      is the best value for any type of homotandem organic solar cells reported so far.

PMID- 29210114
TI  - Atomically Thin Mesoporous Co3 O4 Layers Strongly Coupled with N-rGO Nanosheets
      as High-Performance Bifunctional Catalysts for 1D Knittable Zinc-Air Batteries.
AB  - Under development for next-generation wearable electronics are flexible,
      knittable, and wearable energy-storage devices with high energy density that can
      be integrated into textiles. Herein, knittable fiber-shaped zinc-air batteries
      with high volumetric energy density (36.1 mWh cm-3 ) are fabricated via a facile
      and continuous method with low-cost materials. Furthermore, a high-yield method
      is developed to prepare the key component of the fiber-shaped zinc-air battery,
      i.e., a bifunctional catalyst composed of atomically thin layer-by-layer
      mesoporous Co3 O4 /nitrogen-doped reduced graphene oxide (N-rGO) nanosheets.
      Benefiting from the high surface area, mesoporous structure, and strong
      synergetic effect between the Co3 O4 and N-rGO nanosheets, the bifunctional
      catalyst exhibits high activity and superior durability for oxygen reduction and
      evolution reactions. Compared to a fiber-shaped zinc-air battery using state-of
      the-art Pt/C + RuO2 catalysts, the battery based on these Co3 O4 /N-rGO
      nanosheets demonstrates enhanced and stable electrochemical performance, even
      under severe deformation. Such batteries, for the first time, can be successfully
      knitted into clothes without short circuits under external forces and can power
      various electronic devices and even charge a cellphone.

PMID- 29210115
TI  - Highly Deformable and See-Through Polymer Light-Emitting Diodes with All
      Conducting-Polymer Electrodes.
AB  - Despite the high expectation of deformable and see-through displays for future
      ubiquitous society, current light-emitting diodes (LEDs) fail to meet the desired
      mechanical and optical properties, mainly because of the fragile transparent
      conducting oxides and opaque metal electrodes. Here, by introducing a highly
      conductive nanofibrillated conducting polymer (CP) as both deformable transparent
      anode and cathode, ultraflexible and see-through polymer LEDs (PLEDs) are
      demonstrated. The CP-based PLEDs exhibit outstanding dual-side light-outcoupling
      performance with a high optical transmittance of 75% at a wavelength of 550 nm
      and with an excellent mechanical durability of 9% bending strain. Moreover, the
      CP-based PLEDs fabricated on 4 um thick plastic foils with all-solution
      processing have extremely deformable and foldable light-emitting functionality.
      This approach is expected to open a new avenue for developing wearable and
      attachable transparent displays.

PMID- 29210116
TI  - From targeted fascicular biopsy of major nerve to targeted cutaneous nerve
      biopsy: Implementing clinical anatomy can catalyze a paradigm shift.

PMID- 29210117
TI  - Enantioselective recognition of carboxylic acids by novel fluorescent triazine
      based thiazoles.
AB  - Hydrogen bonding and pi-pi interactions take special part in the
      enantioselectivity task. In this regard, because of having both hydrogen acceptor
      and hydrogen donor groups, melamine derivatives become more of an issue for
      enantioselectivity. In the light of such information, triazine-based chiral,
      fluorescence active novel thiazole derivatives L1 and L2 were designed and
      synthesized from (S)-(-)-2-amino-1-butanol and (1S,2R)-(+)-2-amino-1,2
      diphenylethanol. The structural establishment of these compounds was made by
      spectroscopic methods such as FTIR, 1 H, and 13 C NMR. While the solution of
      these compounds in DMSO did not show any fluorescence emission, it was observed
      that the emission increased 44-fold for L1 and 55-fold for L2 in 95% water,
      similar to the aggregation-induced emission (AIE) characterized compounds. In
      this regard, enantioselective capabilities of these compounds against carboxylic
      acids were tested, and in experiments carried out at a ratio of 40/60 DMSO/H2 O,
      it was determined that R-2ClMA increased the fluorescence emission of L1 chiral
      receptor by 2.59 times compared to S-isomer.

PMID- 29210118
TI  - Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by
      antiangiogenic activity via blocking VEGFR2 signaling.
AB  - Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal
      plants such as Inula helenium, has been identified to have attractive anticancer
      activity. However, its role in the inhibition of angiogenesis during tumor
      development remains unclear. In this study, we found ALA can inhibit the
      proliferation, motility, migration, and tube formation of human umbilical vein
      endothelial cells. ALA also restrained angiogenesis in chick embryo
      chorioallantoic membrane and delayed the growth of human MDA-MB-231 breast cancer
      xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed
      the phosphorylation of vascular endothelial growth factor receptor 2 and its
      downstream protein kinase including PLCgamma1, FAK, Src, and Akt in endothelial
      cells. Taken together, the antiangiogenic activity of ALA and its molecular
      mechanism are identified for the first time, indicating that ALA may be a
      potential drug candidate or lead compound for antiangiogenic cancer therapy.

PMID- 29210119
TI  - Diets rich in saturated fat and fructose induce anxiety and depression-like
      behaviours in the rat: is there a role for lipid peroxidation?
AB  - Epidemiological studies reveal associations between obesity/metabolic syndrome
      and mood disorders. We assessed behavioural changes in rats fed diets enriched in
      fat and fructose in different proportions and correlated the observed alterations
      with biochemical changes induced by the diets. Three groups of rats were used as
      follows: control (C) animals fed regular rat chow, rats fed high-fat diet (HF)
      and rats fed high-fat and high-fructose diet (HFHF). HF and HFHF animals were
      also given a 10% fructose solution as drinking water. Behavioural and biochemical
      parameters were determined. Anxiety was measured by the open-field and the social
      interaction test. Depression-like behaviour was evaluated by the forced swimming
      test. The object recognition test was utilized to assess effects on memory. Diet
      exposed animals displayed signs of anxiety in the open-field (HF rats had reduced
      central time; HFHF rats had reduced number of central entries) and in the social
      interaction test (decreased time of interaction in HF group). In the forced
      swimming test, the immobility time was prolonged in the HFHF group. While
      different measures of anxiety scores correlated with visceral adiposity and
      dyslipidemia, results from both social interaction and forced swimming tests were
      significantly associated with lipid peroxidation, which in turn also correlated
      with the metabolic parameters. The experimental diets did not affect the object
      recognition memory. Both experimental diets induced metabolic derangements in
      rats and provoked similar anxiety- and depression-like behaviours. Lipid
      peroxidation seems to play a role in translating diet-induced metabolic
      alterations into behavioural disorders.

PMID- 29210120
TI  - Endogenous peripheral hydrogen sulfide is propyretic: its permissive role in
      brown adipose tissue thermogenesis in rats.
AB  - NEW FINDINGS: What is the central question of this study? In fever, the most
      striking response in the acute phase reaction of systemic inflammation, plasma H2
      S concentration increases. However, the role of endogenous peripheral H2 S in
      fever is unknown. What is the main finding and its importance? Endogenous
      peripheral H2 S is permissive for increased brown adipose tissue thermogenesis to
      maintain thermal homeostasis in cold environments as well as to mount fever. This
      finding expands the physiological role of the gaseous modulator as a key
      regulator of thermal control in health (thermal homeostasis) and disease (fever
      in systemic inflammation). ABSTRACT: In recent years, hydrogen sulfide (H2 S) has
      been reported as a gaseous modulator acting in several tissues in health and
      disease. In animal models of systemic inflammation, the plasma H2 S concentration
      increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most
      striking response in the acute phase reaction of systemic inflammation is fever,
      but we found no reports of the peripheral action of H2 S on this thermoregulatory
      response. We aimed at investigating whether endogenous systemic H2 S modulates
      LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal
      cavity of male Wistar rats (220-270 g) to record body core temperature. These
      animals received an i.p. injection of a systemic H2 S inhibitor
      (propargylglycine; 50 or 75 mg kg-1 ), immediately followed by an i.p. injection
      of LPS (50 or 2500 MUg kg-1 ), and were exposed to different ambient temperatures
      (16, 22 or 27 degrees C). At 22 degrees C, but not at 27 degrees C,
      propargylglycine at 75 mg kg-1 significantly attenuated (P < 0.0001) the fever
      induced by LPS (50 MUg kg-1 ), indicating a modulatory (permissive) action of
      endogenous peripheral H2 S on brown adipose tissue (BAT) thermogenesis. Evidence
      on the modulatory role of peripheral H2 S in BAT thermogenesis was strengthened
      when we discarded (i) the possible influence of the gas on febrigenic signalling
      (when measuring plasma cytokines), and (ii) its interaction with the nitric oxide
      pathway, and mainly when (iii) we carried out physiological and pharmacological
      activations of BAT. Endogenous peripheral H2 S modulates (permits) BAT activity
      not only in fever but also during maintenance of thermal homeostasis in cold
      environments.

PMID- 29210121
TI  - Proanthocyanidin-rich Pinus radiata bark extract inhibits mast cell-mediated
      anaphylaxis-like reactions.
AB  - Mast cells play a critical role in the effector phase of immediate
      hypersensitivity and allergic reactions. Pinus radiata bark extract exerts
      multiple biological effects and exhibits immunomodulatory and antioxidant
      properties. However, its role in mast cell-mediated anaphylactic reactions has
      not been thoroughly investigated. In this study, we examined the effects of
      proanthocyanidin-rich water extract (PAWE) isolated from P. radiata bark on
      compound 48/80-induced or antidinitrophenyl (DNP) immunoglobulin E (IgE)-mediated
      anaphylaxis-like reactions in vivo. In addition, we evaluated the mechanism
      underlying the inhibitory effect of PAWE on mast cell activation, with a specific
      focus on histamine release, using rat peritoneal mast cells. PAWE attenuated
      compound 48/80-induced or anti-DNP IgE-mediated passive cutaneous anaphylaxis
      like reactions in mice, and it inhibited histamine release triggered by compound
      48/80, ionophore A23187, or anti-DNP IgE in rat peritoneal mast cells in vitro.
      Moreover, PAWE suppressed compound 48/80-elicited calcium uptake in a
      concentration-dependent manner and promoted a transient increase in intracellular
      cyclic adenosine-3',5'-monophosphate levels. Together, these results suggest that
      proanthocyanidin-rich P. radiata bark extract effectively inhibits anaphylaxis
      like reactions.

PMID- 29210122
TI  - Dehydrogenation of N-Heterocycles by Superoxide Ion Generated through Single
      Electron Transfer.
AB  - Nitrogen-containing heteroarene motifs are found in numerous pharmaceuticals,
      natural products, and synthetic materials. Although several elegant methods for
      synthesis of these compounds through dehydrogenation of the corresponding
      saturated heterocycles have been reported, some of the methods are hampered by
      long reaction times, harsh conditions, and the need for catalysts that are not
      readily available. This work reports a novel method for dehydrogenation of N
      heterocycles. Specifically, O2.- generated in situ acts as the oxidant for N
      heterocycle substrates that are susceptible to oxidation through a hydrogen atom
      transfer mechanism. This method provides a general, green route to N
      heteroarenes.

PMID- 29210123
TI  - Differential Modulating Effect of MoS2 on Amyloid Peptide Assemblies.
AB  - The abnormal fibrillogenesis of amyloid peptides such as amyloid fibril and
      senior amyloid plaques, is associated with the pathogenesis of many amyloid
      diseases. Hence, modulation of amyloid assemblies is related to the possible
      pathogenesis of some diseases. Some two-dimensional nanomaterials, that is,
      graphene oxide, tungsten disulfide, exhibit strong modulation effects on the
      amyloid fibrillogenesis. Herein, the modulation effect of molybdenum disulfide on
      two amyloid peptide assemblies based on the label-free techniques is presented,
      including quartz crystal microbalance (QCM), AFM, and CD spectroscopy. MoS2
      presents different modulating effects on the assembly of amyloid-beta peptide (33
      42) [Abeta (33-42)] and amylin (20-29), mainly owing to the distinct affinity
      between amyloid peptides and MoS2 . This is to our knowledge the first report of
      MoS2 as a modulator for amyloid aggregation. It enriches the variety of 2D
      nanomodulators of amyloid fibrillogenesis and explains the mechanism for the self
      assembly of amyloid peptides, and expands the applications of MoS2 in biology.

PMID- 29210124
TI  - A novel herbal composition containing extracts of Boswellia serrata gum resin and
      Aegle marmelos fruit alleviates symptoms of asthma in a placebo controlled double
      blind clinical study.
AB  - LI13109F is a novel herbal composition containing the extracts of Boswellia
      serrata gum resin and Aegle marmelos fruit. This composition dampens leukotriene
      dependent inflammatory reactions via inhibiting 5-lipoxygenase pathway. In a
      Sephadex LH-20 induced airway inflammation model of Sprague Dawley rats, LI13109F
      significantly reduced infiltrated granulocyte population in the bronco-alveolar
      lavage fluid and normalized Th1/Th2 cytokine balance. Further, a 56-day placebo
      controlled and randomized double blind study (Clinical Trial Registration No.
      CTRI/2016/10/007393) on subjects with mild to moderate asthma has evaluated the
      clinical efficacy of LI13109F. The study subjects received either 200 mg/day of
      LI13109F (n = 18) or a similar dosage of placebo (n = 18). At the end of the
      trial period, LI13109F conferred significant improvements in the clinical
      parameters; the emotional function (p = .0305) and asthma symptoms scores (p =
      .0002) were improved even at 14 days, compared with the placebo. Further, 56 days
      supplementation of LI13109F resulted in significant increase in serum IFN-gamma
      (p = .0014) and reduction in IL-4 (p = .0497), compared with placebo. LI13109F
      supplementation did not yield any serious adverse events or any abnormal
      observations in routine laboratory examinations during the study. Together, these
      observations suggest that LI13109F (AlvioLife(r)) is tolerable and an effective
      intervention for management of mild to moderate asthma such as airway
      inflammation.

PMID- 29210125
TI  - A Water-Stable Luminescent ZnII Metal-Organic Framework as Chemosensor for High
      Efficiency Detection of CrVI -Anions (Cr2 O72- and CrO42- ) in Aqueous Solution.
AB  - A new luminescent ZnII -MOF with 1D triangular channels along the b axis, namely
      NUM-5, has been successfully assembled and well characterized, which features
      good stability, especially in aqueous solution. Interestingly, this compound
      exhibits a fast, sensitive and selective luminescence quenching response towards
      CrVI (Cr2 O72- /CrO42- ) in aqueous solution. The detection limits towards Cr2
      O72- and CrO42- ions are estimated to be 0.7 and 0.3 ppm, respectively, which are
      among the lowest detection limits reported for the MOF-based fluorescent probes
      that can simultaneously detect Cr2 O72- and CrO42- in aqueous environment. The
      possible detection mechanism has been discussed in detail. Moreover, it can be
      easily regenerated after detection experiments, indicative of excellent
      recyclability. All these results suggest NUM-5 to be a highly selective and
      recyclable luminescent sensing material for the quantitative detection of CrVI
      anions in aqueous solution.

PMID- 29210126
TI  - Crosslink between calcium and sodium signalling.
AB  - NEW FINDINGS: What is the topic of this review? This paper overviews the links
      between Ca2+ and Na+ signalling in various types of cells. What advances does it
      highlight? This paper highlights the general importance of ionic signalling and
      overviews the molecular mechanisms linking Na+ and Ca2+ dynamics. In particular,
      the narrative focuses on the molecular physiology of plasmalemmal and
      mitochondrial Na+ -Ca2+ exchangers and plasmalemmal transient receptor potential
      channels. Functional consequences of Ca2+ and Na+ signalling for co-ordination of
      neuronal activity with astroglial homeostatic pathways fundamental for synaptic
      transmission are discussed. ABSTRACT: Transmembrane ionic gradients, which are an
      indispensable feature of life, are used for generation of cytosolic ionic signals
      that regulate a host of cellular functions. Intracellular signalling mediated by
      Ca2+ and Na+ is tightly linked through several molecular pathways that generate
      Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor
      potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with
      generation of Na+ and Ca2+ currents. The plasmalemmal Na+ -Ca2+ exchanger (NCX)
      flickers between forward and reverse mode to co-ordinate the influx and efflux of
      both ions with membrane polarization and cytosolic ion concentrations. The
      mitochondrial calcium uniporter channel (MCU) and mitochondrial Na+ -Ca2+
      exchanger (NCLX) mediate Ca2+ entry into and release from this organelle and
      couple cytosolic Ca2+ and Na+ fluctuations with cellular energetics. Cellular
      Ca2+ and Na+ signalling controls numerous functional responses and, in the CNS,
      provides for fast regulation of astroglial homeostatic cascades that are crucial
      for maintenance of synaptic transmission.

PMID- 29210127
TI  - Highly Luminescent CsPbX3 (X=Cl, Br, I) Nanocrystals Achieved by a Rapid Anion
      Exchange at Room Temperature.
AB  - Cesium lead halide perovskite (CsPbX3 ) nanocrystals (NCs) exhibit an excellent
      photoelectric performance, which is directly governed by fine-tuning of the
      composition and preparation of materials with a special phase structure and
      morphology. However, it is still facing challenges to achieve highly stable and
      luminescent CsPbX3 NCs at room temperature. Herein, we report on a novel exchange
      reaction, in which metal halides MX2 (M=Zn, Mg, Cu, or Ca; X=Cl, Br, or I) solids
      act as anion source to directly prepare CsPbX3 NCs at room temperature without
      any pretreatment. Introducing small amount of oleic acid or oleylamine speed up
      the exchange reaction through different promotion mechanisms. Oleic acid
      coordinates to the surface of the NCs, which increases the reaction activity, and
      oleylamine greatly enhances the dissolution of ZnCl2 . XRD and TEM tests
      demonstrate that the cubic phase structure and the morphology of the parent
      CsPbX3 were well preserved. Moreover, the band-gap energies and photoluminescence
      (PL) spectra were readily tunable over the entire visible spectral region of
      lambda=406-685 nm. Our findings could open up the possibilities of using metal
      halide solids as new anion sources to prepare high-quality CsPbX3 NCs at room
      temperature.

PMID- 29210128
TI  - One-pot synthesis and characterization CdTe:Zn2+ quantum dots and its molecular
      interaction with calf thymus DNA.
AB  - Tremendous research efforts have been dedicated to fabricating high-quality Zn
      doped CdTe quantum dots (QDs) for any potential biomedical applications. In
      particular, the correlation of issues regarding how QDs interact with DNA is of
      greatest importance. Herein, a pH-responsive study of the interactions between
      CdTe:Zn2+ quantum dots with 4 different sizes and calf thymus DNA (ctDNA) was
      conducted using multispectroscopic techniques and electrochemical investigation.
      Fluorescence studies revealed that this interaction process is predominantly a
      static process and groove binding was the main binding mode for CdTe:Zn2+ QDs to
      ctDNA. The calculated negative values of enthalpy (-45.06 kJ mol-1 ) and entropy
      (-133.62 J mol-1  K-1 ) with temperature changes indicated that the hydrogen
      bonds and van der Waals interactions played major roles in the reaction.
      Furthermore, circular dichroism spectroscopy and Fourier transform infrared
      spectrometry analyses indicate that the normal conformation of ctDNA is
      discombobulated by CdTe:Zn2+ QDs. In addition, the electrochemical behavior of
      the affinity of CdTe:Zn2+ QDs for ctDNA agreed well with the results obtained
      from fluorescence experiments. This study might be meaningful for understanding
      the molecular binding mechanism of QDs for DNA and provides a basis for QD
      labeled systems.

PMID- 29210130
TI  - Home setting after stroke, facilitators and barriers: A systematic literature
      review.
AB  - This paper seeks to improve the understanding of the interaction between patients
      with stroke and the physical environment in their home settings. Stroke care is
      increasingly performed in the patient's home. Therefore, a systematic review was
      conducted to identify the existing knowledge about facilitators and barriers in
      the physical environment of home settings for the stroke rehabilitation process.
      Based upon Arksey and O'Malley's framework, a Boolean search strategy was
      performed in the databases; CINAHL, Medline, Web of Science and Scopus. Fifteen
      articles were retained from the literature search conducted between August and
      November 2016, and two researchers independently assessed their quality based on
      the Swedish Council on Health Technology Assessment guidelines. The results
      suggest that despite the healthcare system's ongoing shift towards home-based
      rehabilitation, the role played by the physical environment of home settings is
      still considered a side finding. Moreover, the research appears to focus mainly
      on how this environment supports mobility and activities of daily living, whereas
      information regarding the psychosocial and emotional processes that mediate the
      interaction between stroke survivors and their home setting are missing. A lack
      of information was also found with regard to the influence of different
      geographic locations on the stroke rehabilitation process. Future investigations
      are therefore needed to advance the understanding of the role played by the
      physical environment of home settings in supporting stroke recovery.

PMID- 29210129
TI  - Effect of resveratrol and pterostilbene on aging and longevity.
AB  - Over the past years, several studies have found that foods rich in polyphenols
      protect against age-related disease, such as atherosclerosis, cardiovascular
      disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D),
      hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the
      polyphenol found in grape and blueberries, have beneficial effects as anti-aging
      compounds through modulating the hallmarks of aging, including oxidative damage,
      inflammation, telomere attrition and cell senescence. In this review, we discuss
      the relationship between resveratrol and pterostilbene and possible aging
      biomarker, including oxidative stress, inflammation, and high-calorie diets.
      Moreover, we also discuss the positive effect of resveratrol and pterostilbene on
      lifespan, aged-related disease, and health maintenance. Furthermore, we summarize
      a variety of important mechanisms modulated by resveratrol and pterostilbene
      possibly involved in attenuating age-associated disorders. Overall, we describe
      resveratrol and pterostilbene potential for prevention or treatment of several
      age-related diseases by modulating age-related mechanisms. (c) 2017 BioFactors,
      44(1):69-82, 2018.

PMID- 29210131
TI  - Allergens produce serine proteases-dependent distinct release of metabolite DAMPs
      in human bronchial epithelial cells.
AB  - BACKGROUND: The respiratory epithelium is a major site for disease interaction
      with inhaled allergens. Additional to IgE-dependent effects, allergens contain
      proteases that may stimulate human bronchial epithelial cells (HBECs) through
      protease-activated receptors, causing the release of mediators important in
      driving Th2-mediated immune responses. OBJECTIVE: We aimed to investigate whether
      different allergens induce metabolite DAMPs such as ATP and uric acid (UA)
      release in HBECs. METHODS: HBECs (BEAS-2B cell line) were exposed to different
      allergen extracts; house dust mite (HDM), Alternaria alternata, Artemisia
      vulgaris and Betula pendula and UA, ATP, IL-8 and IL-33 release were measured.
      Allergen extracts were heat-inactivated or pre-incubated with serine (AEBSF) or
      cysteine (E64) protease inhibitors to study the involvement of protease activity
      in ATP, UA and IL-8 release. HDM-induced release of UA was studied in a mouse
      model of allergic inflammation. RESULTS: All allergens caused dose-dependent
      rapid release of ATP and IL-8, but only HDM induced UA release from HBECs. HDM
      also caused release of UA in vivo in our mouse model of allergic inflammation.
      ATP release by all 4 allergen extracts was significantly reduced by heat
      inactivation and by serine protease inhibitors. Similarly, the HDM-induced UA
      release was also abrogated by heat-inactivation of HDM extract and dependent on
      serine proteases. Furthermore, allergen-induced IL-8 mRNA expression was
      inhibited by serine protease inhibitors. CONCLUSIONS AND CLINICAL RELEVANCE: ATP
      was released by all 4 allergens in HBECs supporting the role of ATP involvement
      in asthma pathology. However, HDM stands out by its capacity to cause UA release,
      which is of interest in view of the proposed role of UA in early initiation of
      allergic asthma. Although serine proteases may be involved in the activity of all
      the studied allergens, further work is warranted to explain the differences
      between HDM and the other 3 allergens regarding the effects on UA release.

PMID- 29210132
TI  - Community pharmacists' opinions on skill-mix and delegation in England.
AB  - OBJECTIVES: Following the 2005 contractual framework amendment, the expanding
      role of community pharmacy team members required a shift in entrenched views on
      roles and duties. This study aimed to report on community pharmacists' opinions
      on skill mix and explore how they can be addressed so that skill mix may be
      optimised. METHODS: An invitation to complete an online questionnaire was
      distributed via email, marked for the attention of the lead pharmacist. Following
      a low response, a paper-based questionnaire was sent to all community pharmacies
      in England (n = 11,816). Questions elicited data about the respondent, the
      pharmacy (including staffing profile) and opinions on skill mix. KEY FINDINGS: A
      total of 1154 returns were received, representing a 10% response rate. Of these,
      most were pharmacy chains (76%; n = 877), with 5-9 staff (54%; n = 600); commonly
      open 40-49 hours (42%; n = 487), dispensing <6000 prescriptions per week (41%, n
      = 533). From 26 statements on skill mix, three factors were identified by
      principal-components factor analysis: 'working well', 'feeling the pressure' and
      'open to development'. Characteristics associated with 'working well': pharmacy
      owners, single businesses, with pharmacy technician(s), dispensing fewer
      prescriptions and open shorter hours. Characteristics associated with 'feeling
      the pressure': pharmacy chains, open longer hours, large numbers of prescriptions
      and relief pharmacists. Characteristics associated with 'open to development':
      recently qualified, second pharmacists, working longer hours, chains and
      dispensing lower numbers of prescriptions. CONCLUSIONS: Although limited by a low
      response, results suggest being in a position to influence (more experienced,
      business owners) may be associated with more positive opinions. Further training
      (including about legalities and leadership) could contribute to optimising skill
      mix in community pharmacies.

PMID- 29210133
TI  - Health disparities across education: The role of differential reporting error.
AB  - One of the most robust findings in health economics is that higher educated
      individuals tend to be in better health. This paper tests whether health
      disparities across education are to some extent due to differences in reporting
      error across education. We test this hypothesis using data from the pooled
      National Health and Nutrition Examination Survey (NHANES) for 1999-2012, which
      include both self-reports and objective verification for an extensive set of
      health behaviors and conditions, including smoking, obesity, high blood pressure,
      high cholesterol, and diabetes. We find that college graduates are more likely to
      give false negative reports of obesity and high total cholesterol; one possible
      explanation for this is social desirability bias. However, college graduates are
      also significantly less likely to give false positive reports of smoking,
      obesity, and high cholesterol. Because there are far more truly negative people
      (who are less likely to give a false positive report) than more truly positive
      people (who are more likely to give a false negative report), we find that
      college graduates report their health significantly more accurately overall.

PMID- 29210134
TI  - Socio-economic status and physicians' treatment decisions.
AB  - This paper studies the relationship between patients' socio-economic status and
      general practitioners' (GPs') service provision by exploiting administrative
      patient-level data with information on consultation length, medical tests, and
      fee payments for each visit in Norway over a 5-year period (2008-2012). To reduce
      patient heterogeneity, we limit the sample to a given condition, diabetes type
      II, that is treated almost exclusively in primary care. We estimate GP fixed
      effect models and control for a wide set of patient characteristics. Our results
      show that, for each visit, patients with low education get shorter consultations
      but more medical tests, patients with low income get less of both, and patients
      with low education/income get less services in monetary terms. We also find that,
      during a year, patients with low education/income visit the GP more often and
      receive more services in monetary terms. Thus, GPs treat patients differently
      according to their socio-economic status, but we find no support for a social
      gradient.

PMID- 29210135
TI  - Functional Polymer Opals and Porous Materials by Shear-Induced Assembly of Tailor
      Made Particles.
AB  - Photonic band-gap materials attract enormous attention as potential candidates
      for a steadily increasing variety of applications. Based on the preparation of
      easily scalable monodisperse colloids, such optically attractive photonic
      materials can be prepared by an inexpensive and convenient bottom-up process.
      Artificial polymer opals can be prepared by shear-induced assembly of core/shell
      particles, yielding reversibly stretch-tunable materials with intriguing
      structural colors. This feature article highlights recent developments of
      core/shell particle design and shear-induced opal formation with focus on the
      combination of hard and soft materials as well as crosslinking strategies.
      Structure formation of opal materials relies on both the tailored core/shell
      architecture and the parameters for polymer processing. The emphasis of this
      feature article is on elucidating the particle design and incorporation of
      addressable moieties, i.e., stimuli-responsive polymers as well as elaborated
      crosslinking strategies for the preparation of smart (inverse) opal films,
      inorganic/organic opals, and ceramic precursors by shear-induced ordering.

PMID- 29210136
TI  - Identifying acceptable components for home-based health promotion services for
      older people with mild frailty: A qualitative study.
AB  - Mild frailty is common in later life, increasing the risk of hospitalisation,
      loss of independence and premature death. Targeted health promotion services may
      reduce adverse outcomes and increase quality of life; however, effective, well
      developed theory-based interventions are lacking. We aimed to explore perceptions
      of health promotion behaviours undertaken by older people with mild frailty,
      barriers and facilitators to engagement, and identify potential components for
      new home-based health promotion services. We carried out 17 semi-structured
      qualitative interviews and six focus groups with 53 stakeholders, including 14
      mildly frail older people, 12 family carers, 19 community health and social care
      professionals, and 8 homecare workers, in one urban and one semi-rural area of
      England. Transcripts were thematically analysed. Older people with mild frailty
      reported engaging in a variety of lifestyle behaviours to promote health and well
      being. Key barriers or facilitators to engaging in these included transport,
      knowledge of local services, social support and acceptance of personal
      limitations. Older people, carers and professionals agreed that any new service
      should address social networks and mobility and tailor other content to each
      individual. Services should aim to increase motivation through focussing on
      independence and facilitate older people to continue carrying out behaviours that
      improve their well-being, as well as provide information, motivation,
      psychological support and practical support. Stakeholders agreed services should
      be delivered over a sustained period by trained non-specialist workers. New
      services including these components are likely to be acceptable to older people
      with mild frailty.

PMID- 29210138
TI  - Endovascular shedding markers in patients with heart failure with reduced
      ejection fraction: Results from a single-center exploratory study.
AB  - BACKGROUND: Endothelial glycocalyx degradation has been associated with multiple
      pathophysiological processes in cardiovascular disease. AIMS: To explore the role
      of glycocalyx shedding markers in pathophysiology of HFrEF. METHODS: In 123 HFrEF
      patients, the concentration, prognostic value, and association of glycocalyx
      shedding markers with other disease processes were investigated. RESULTS: Median
      HA levels and syndecan-1 levels in HFrEF patients were, respectively, 29.4
      (10.7;61.6) ng/mL and 48.5 (33.6;80.8) ng/mL. Overall, HA-levels were
      significantly higher in HFrEF patients compared to healthy subjects, but only 31%
      of HFrEF patients had HA-levels above the cutoff of normal. There was no
      significant difference among HFrEF patients and healthy subjects regarding
      syndecan-1 levels. HFrEF patients with elevated HA-levels had a significantly
      worse outcome (log rank = 0.01) which remained significant after correction for
      established risk factors (HR 2.53 (1.13-5.69); P = .024). There was no
      significant relation between levels of shedding markers and neurohumoral
      activation (PRA, serum aldosterone, NT-proBNP), myocardial injury (HS-trop),
      inflammation (CRP), or other baseline characteristics. CONCLUSIONS: The
      glycocalyx shedding marker HA is significantly elevated in a subgroup of HFrEF
      patients and an independent predictor for worse clinical outcome. Glycocalyx
      shedding might be an additional factor in the pathophysiology of HF which
      warrants further investigation.

PMID- 29210137
TI  - Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a
      decrease in sublingual perfusion.
AB  - OBJECTIVE: To determine the human dose-response relationship between a stepwise
      increase in arterial oxygen tension and its associated changes in DO2 and
      sublingual microcirculatory perfusion. METHODS: Fifteen healthy volunteers
      breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen
      tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing
      oxygen). Systemic hemodynamics were measured continuously by the volume-clamp
      method. At the end of each period, the sublingual microcirculation was assessed
      by SDF. RESULTS: Systemic DO2 was unchanged throughout the study (Pslope  = .8).
      PVD decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18,
      Pslope  = .001). CI decreased linearly (max -10%, SD10, Pslope  < .001) due to a
      reduction in HR (max -10%, SD7, Pslope  = .009). There were no changes in stroke
      volume or MAP. Most changes became apparent above an arterial oxygen tension of
      20 kPa. CONCLUSIONS: In healthy volunteers, supraphysiological arterial oxygen
      tensions have no effect on systemic DO2 . Sublingual microcirculatory PVD
      decreased in a dose-dependent fashion. All hemodynamic changes appear negligible
      up to an arterial oxygen tension of 20 kPa.

PMID- 29210139
TI  - How not to argue against nursing associates.

PMID- 29210140
TI  - Measuring cancer caregiver health literacy: Validation of the Health Literacy of
      Caregivers Scale-Cancer (HLCS-C) in an Australian population.
AB  - Caregivers have been largely neglected in health literacy measurement. We assess
      the construct validity, and internal consistency of the Health Literacy of
      Caregivers Scale-Cancer (HLCS-C), and present a revised, psychometrically robust
      scale. Using data from 297 cancer caregivers (12.4% response rate) recruited from
      Melbourne, Australia between January-July 2014, confirmatory factor analysis
      (CFA) was conducted to evaluate the HLCS-C's proposed factor structure. Items
      were evaluated for: item difficulty, unidimensionality and overall item fit
      within their domain. Item-threshold-ordering was examined though one-parameter
      Item Response Theory models. Internal consistency was assessed using Raykov's
      reliability coefficient. CFA results identified 42 poorly performing/redundant
      items which were subsequently removed. A 10-factor model was fitted to 46
      acceptable items with no correlated residuals or factor cross-loadings accepted.
      Adequate fit was revealed (chi2WLSMV  = 1463.807[df = 944], p < .001, RMSEA =
      0.043, CFI = 0.980, TLI = 0.978, WRMR = 1.00). Ten domains were identified:
      Proactivity and determination to seek information; Adequate information about
      cancer and cancer management; Supported by healthcare providers (HCP) to
      understand information; Social support; Cancer-related communication with the
      care recipient (CR); Understanding CR needs and preferences; Self-care;
      Understanding the healthcare system; Capacity to process health information; and
      Active engagement with HCP. Internal consistency was adequate across domains
      (0.78-0.92). The revised HLCS-C demonstrated good structural, convergent, and
      discriminant validity, and high internal consistency. The scale may be useful for
      the development and evaluation of caregiver interventions.

PMID- 29210141
TI  - Extending Addiction's conflict of interest policy to cover the emerging cannabis
      industry.

PMID- 29210142
TI  - Internal validation of Medicaid Analytic eXtract (MAX) data capture for
      comprehensive managed care plan enrollees from 2007 to 2010.
AB  - PURPOSE: Because of concerns over incomplete medical encounter capture in
      Medicaid capitated comprehensive managed care (CMC) plans, researchers have
      traditionally confined analyses to fee-for-service (FFS) enrollees. We aimed to
      evaluate the usability of data for CMC enrollees in Medicaid Analytic eXtract
      (MAX) files for 29 states from 2007 to 2010. METHODS: We applied 7 measures to
      MAX inpatient, other therapy, and prescription drug files for each state and
      study year. Four measures were based on "connectivity" criteria where we expected
      use of a select essential service to be closely connected to another, resulting
      in "service pairs." Three measures were based on "continuity" criteria where we
      expected patients to continue chronically used services or treatments when they
      switched enrollment from FFS to CMC plans. High proportions of continuity and
      comparable proportions of patients with complete service pairs relative to FFS
      enrollees may suggest complete data capture for CMC enrollees. Data of states
      that met preset criteria were considered usable for research and policy analyses.
      RESULTS: The completeness of CMC enrollees' data in MAX varied by states. Among
      22 states having at least 5% CMC plan enrollment, data of 12 states met our
      quality standard and were considered usable starting in 2007. Four states had
      usable data starting in 2008 and one in 2009. CONCLUSIONS: The completeness of
      CMC enrollees' data in MAX improved over the study period. In 17 out of 29
      states, CMC enrollees' data in selected years were comparable with FFS enrollees
      and can be considered for use in analysis.

PMID- 29210143
TI  - Sudden death in paediatrics as a traumatic experience for critical care nurses.
AB  - BACKGROUND: Research shows that nurses working in critical care units and in
      particular, paediatric units, are at risk of developing symptoms of secondary
      traumatic stress (STS). However, little attention has been given to this
      phenomenon when associated with situations of sudden death in paediatrics. AIM:
      This study aimed to examine the impact of sudden death in paediatrics on nurses
      working in paediatrics critical care units and to explore nurses' experiences of
      this event. METHODS: This study used a mixed-methods design. The Impact of Event
      Scale - Revised was used for investigating the presence of STS symptoms. In
      addition, an interview was conducted with six nurses. RESULTS: Fifty-seven
      percent of nurses responded to the surveys and six nurses were interviewed. The
      results showed that the sudden death of children and adolescents is an event that
      elicits symptoms of STS in nurses. The quantitative assessment, revealed that
      19.4% presented total scores indicating high impact. The participants interviewed
      described experiences of subjective distress, such as intrusive thoughts,
      avoidance and hyperarousal. Other factors were also reported as influencing the
      experience of the sudden death of a child/adolescent, namely, the child's age,
      the cause of death and the family's reaction to the loss. According to the
      participants, the emotional impact was also determined by parenthood, previous
      training and professional experience. CONCLUSIONS: Sudden death in paediatric
      critical care units is one of the most difficult situations in nursing practice
      and elicits STS symptoms, which may severely impact the physical and
      psychological health of nurses and ultimately affect the quality of the provided
      care. RELEVANCE FOR CLINICAL PRACTICE: This study emphasizes the need for
      promoting better conditions for professional practice, namely, with regard to
      emotional support, as well as training programmes for skills development in the
      area of management of traumatic situations and of communication with clients.

PMID- 29210144
TI  - Adolescent impulsivity as a sex-dependent and subtype-dependent predictor of
      impulsivity, alcohol drinking and dopamine D2 receptor expression in adult rats.
AB  - Impulsivity is a personality trait associated with a heightened risk for drug use
      and other psychiatric conditions. Because impulsivity-related disorders typically
      emerge during adolescence, there has been interest in exploring methods for
      identifying adolescents that will be at risk to develop substance use disorders
      in adulthood. Here, we used a rodent model to assess inhibitory control
      (impulsive action) and impulsive decision making (impulsive choice) during
      adolescence (43-50 days old) or adulthood (93-100 days old) and then examined the
      impact of development on these impulsivity traits by re-testing rats 50 days
      later. Impulsive action was not stable from adolescence to adulthood in male rats
      and was lowest in adult male rats, relative to adolescents and female rats.
      Impulsive choice was stable across development and unaffected by age or sex.
      Next, we examined the connection between our model of impulsivity and two
      measures relevant to substance abuse research: the initiation of voluntary
      alcohol drinking and dopamine D2 receptor (D2 R) expression in the prelimbic
      prefrontal cortex. Consumption of saccharin-sweetened ethanol during 30-minute
      sessions in adulthood was associated with adolescent, but not adult, impulsive
      action, particularly in male rats. Prelimbic D2 R expression was reduced in
      individuals with high levels of impulsive choice, and this relationship appeared
      to be strongest among female rats. The results of this study demonstrate that
      impulsive choice, along with its connection to D2 R expression, is relatively
      unchanged by the process of development. For impulsive action, however,
      individual levels of impulsivity during adolescence predict drinking in adulthood
      despite changes in the measure during development.

PMID- 29210145
TI  - Squamous cell carcinoma of unknown primary of the head and neck: Favorable
      prognostic factors comparable to those in oropharyngeal cancer.
AB  - BACKGROUND: Treatment for squamous cell carcinoma (SCC) of unknown primary
      consists of radiotherapy (RT) +/- chemotherapy or neck dissection +/- adjuvant
      RT/chemoradiotherapy (CRT). We compared these strategies and identified
      prognostic factors. METHODS: From 1993 to 2015, 75 patients with SCC of unknown
      primary had RT-based or surgery-based treatment. Primary endpoints were overall
      survival (OS) and disease-free survival (DFS). Event-time distributions were
      estimated using the Kaplan-Meier method. RESULTS: Five-year OS and DFS for RT
      based and surgery-based treatments were similar (OS 73% vs 68%, respectively; DFS
      65% vs 64%, respectively). Among 38 patients with p16 data, 76% were p16 positive
      and showed improved 5-year DFS (90% vs 33%; P = .001) and OS (96% vs 33%; P <
      .001). Smoking history <=10 pack-years conferred better 5-year DFS (88% vs 49%; P
      < .001) and OS (91% vs 59%; P < .001). CONCLUSION: RT-based and surgery-based
      treatments produced similar outcomes. Patients with p16-positive disease with
      <=10 pack-years of smoking history and limited nodal stage constitute a "low
      risk" group in SCC of unknown primary similar to that in oropharyngeal cancer.

PMID- 29210146
TI  - Central administration of galanin N-terminal fragment 1-15 decreases the
      voluntary alcohol intake in rats.
AB  - Alcohol consumption is considered a major risk factor for disease and mortality
      worldwide. In the absence of effective treatments in alcohol use disorders, it is
      important to find new biological targets that could modulate alcohol consumption.
      We tested the role of the N-terminal galanin fragment (1-15) [GAL(1-15)] in
      voluntary ethanol consumption in rats using the two-bottle choice paradigm as
      well as compare the effects of GAL(1-15) with the whole molecule of GAL. We
      describe for the first time that GAL(1-15), via central mechanisms, induces a
      strong reduction in preference and ethanol consumption in rats. These effects
      were significantly different than GAL. GAL receptor (GALR) 2 was involved in
      these effects, because the specific GALR2 antagonist M871 blocked GAL(1-15)
      mediated actions in preference and ethanol intake. Importantly, the mechanism of
      this action involves changes in GALR expression and also in immediate-early gene
      C-Fos and receptors-internalization-related gene Rab5 in the striatum. The
      relevance of the striatum as a target for GAL(1-15) was supported by the effect
      of GAL(1-15) on the locomotor activity of rats after ethanol administration.
      These results may give the basis for the development of novel therapeutics
      strategies using GAL(1-15) analogues for the treatment of alcohol use disorders
      in humans.

PMID- 29210147
TI  - Drug exposure and the risk of multiple sclerosis: A systematic review.
AB  - BACKGROUND: Several environmental and lifestyle factors have been associated with
      multiple sclerosis (MS) risk, including some pharmacological treatments. We
      systematically reviewed the literature on prescription drug exposure and MS risk.
      METHODS: Six databases were searched for original observational studies reporting
      drug exposure and MS risk published before 2017. RESULTS: Thirteen articles
      fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was
      associated with MS (adjusted hazard ratio (adj.HR = 1.34;95% CI:0.81-2.20; adj.HR
      = 1.30;95%CI:0.44-3.80, respectively). Four studies explored oral contraceptive
      exposure and reported no association with MS; while a single study found an
      increased risk (odds ratio [adj.OR] = 1.52;95%CI:1.21-1.91). While penicillin
      exposure was associated with reduced risk of developing MS (adj.OR =
      0.5;95%CI:0.3-0.9), a later study observed an elevated risk for penicillin
      (adj.OR = 1.21;95%CI:1.10-1.27) and all antibiotics (adj.OR = 1.41;95%CI:1.29
      1.53), which was potentially attributed to underlying infection. Anti-tumor
      necrosis factor-alpha (TNFalpha) was not associated with MS risk in persons with
      inflammatory bowel disease (standard morbidity ratio = 4.2;95%CI:0.1-23.0) and
      arthritis (standardized incidence ratio = 1.38;95%CI:0.69-2.77); however, men
      exposed to anti-TNFalpha who also had arthritis and individuals with ankylosing
      spondylitis were at an increased risk (standardized incidence ratios =
      3.91;95%CI:1.47-10.42 and 3.48;95%CI:1.45-8.37, respectively). A reduced risk of
      MS was observed with exposure to the beta2-adrenergic agonist fenoterol (adj.OR =
      0.58;95%CI:0.45-0.76), and the sedating histamine 1-receptor antagonists (adj.OR
      = 0.2;95%CI:0.1-0.8), but not the non-sedating equivalent (adj.OR = 0.8;95%CI:0.4
      1.6). CONCLUSIONS: The suggestion that some drugs may prevent MS is intriguing
      and warrants further study. In addition, further pharmacovigilance is needed to
      assess the safety of anti-TNFalpha drugs in specific populations in the context
      of MS risk.

PMID- 29210148
TI  - Sex differences in adult mortality rate mediated by early-life environmental
      conditions.
AB  - Variation in sex differences is affected by both genetic and environmental
      variation, with rapid change in sex differences being more likely due to
      environmental change. One case of rapid change in sex differences is human
      lifespan, which has become increasingly female-biased in recent centuries. Long
      term consequences of variation in the early-life environment may, in part,
      explain such variation in sex differences, but whether the early-life environment
      mediates sex differences in life-history traits is poorly understood in animals.
      Combining longitudinal data on 60 cohorts of pre-industrial Finns with
      environmental data, we show that the early-life environment is associated with
      sex differences in adult mortality and expected lifespan. Specifically, low
      infant survival rates and high rye yields (an important food source) in early
      life are associated with female-bias in adult lifespan. These results support the
      hypothesis that environmental change has the potential to affect sex differences
      in life-history traits in natural populations of long-lived mammals.

PMID- 29210149
TI  - Retinal vascular complications associated with interferon-ribavirin therapy for
      chronic hepatitis C: A population-based study.
AB  - PURPOSE: To investigate the incidence of retinal vascular complications and risk
      factors in patients with chronic hepatitis C receiving interferon-ribavirin
      therapy in Taiwan. METHODS: By using the Taiwan National Health Insurance
      Research Database, we compared the incidence of retinal vascular complications
      between patients receiving and not receiving interferon-ribavirin treatment. The
      exposure and nonexposure groups were randomly 1:1 frequency-matched according to
      age, sex, income, urbanization level, hypertension, and diabetes. Incidence of
      each retinal vascular complication and hazard ratios were assessed in the follow
      up evaluation. RESULTS: Of the sample of 4736 patients, a total of 182 patients
      (3.84%) developed retinopathy during the follow-up period, of which 110 patients
      (4.65%) received interferon-ribavirin therapy and 72 patients (3.04%) did not
      receive interferon-ribavirin therapy. After multivariate adjustments, the risk of
      retinopathy during the follow-up period was 1.533 (95% confidence interval [CI],
      1.139-2.064; P = .0048) times higher in patients receiving interferon-ribavirin
      therapy than in those in the comparison cohort not receiving the therapy.
      Patients with hypertension compared with those without it (adjusted hazard ratio,
      1.530; 95% CI, 1.069-2.135; P = .0125) also had an increased risk of retinopathy.
      CONCLUSIONS: Interferon-ribavirin therapy was associated with a 53.3% increased
      risk of retinal vascular complications compared with not receiving the therapy.
      Regular ophthalmologic examination is essential for patients receiving interferon
      ribavirin, particularly those with hypertension.

PMID- 29210150
TI  - Research Leads to Approved Therapies in the New Era of Living Medicine.

PMID- 29210151
TI  - Re: Inositol treatment of anovulation in women with polycystic ovary syndrome: a
      meta-analysis of randomised trials.

PMID- 29210152
TI  - HbAHP-25 attenuates HIV-1 gp120 mediated inflammation and barrier dysfunction.
AB  - OBJECTIVES: Development of HbAHP-25, a peptide that prevents HIV-1 entry into
      cells by blocking gp120-CD4 interaction, as a topical anti-HIV drug, necessitates
      that it is first tested for toxic or abrasive effects on genital epithelial cells
      and also on the vaginal microbiome. The present study was, therefore, undertaken
      to investigate whether: (1) HbAHP-25 has any adverse effect on growth and
      membrane integrity of various cell lines, and (2) HbAHP-25 neutralizes gp120
      mediated insults on genital epithelial cells. METHODS: MTT and trans-epithelial
      resistance (TER) assays were performed to assess the viability and integrity of
      epithelial cells. Real-time PCR and Immunofluorescence/Western blotting were used
      to decipher the expression of tight junction proteins, at the mRNA and protein
      levels, respectively. A multiplex cytokine assay was performed to quantify the
      cytokines. RESULTS: HbAHP-25 had no adverse effect on the viability of VK2/E6E7,
      End1/E6E7, Ect1/E6E7 and HEC-1A cells, and also on growth of lactobacilli. The
      barrier integrity of HbAHP-25-treated cells remained unaltered. Expression of
      tight junction proteins, Claudin-1 and ZO-1, at transcript and protein levels,
      remained unaltered in HbAHP-25-treated HEC-1A cells. Interestingly, HbAHP-25
      treatment prevented the breach of barrier integrity caused by gp120. Further,
      HbAHP-25 did not elicit the expression of inflammatory cytokines. Instead, the in
      vitro induction of inflammatory cytokines by gp120 was also abrogated in the
      presence of HbAHP-25. CONCLUSION: HbAHP-25 is exceedingly safe to genital
      epithelial cells and attenuates HIV-1 gp120-mediated barrier dysfunction by
      limiting excessive inflammation. This study provides significant evidences in the
      favor of HbAHP-25's potential as a topical anti-HIV agent.

PMID- 29210153
TI  - Re: Comparison of management regimens following ultrasound diagnosis of nontubal
      ectopic pregnancies: a retrospective cohort study: Interstitial pregnancies: a
      diagnosis and treatment challenge.

PMID- 29210154
TI  - Re: Insights from Outside BJOG. Research Snippets: Further evidence of serious
      harm of early cord clamping.

PMID- 29210155
TI  - A 30 nm Nanopore Electrode: Facile Fabrication and Direct Insights into the
      Intrinsic Feature of Single Nanoparticle Collisions.
AB  - Clarifying the hidden but intrinsic feature of single nanoparticles by
      nanoelectrochemistry could help understand its potential for diverse
      applications. The uncontrolled interface and bandwidth limitation in the
      electrochemical measurement put the obstacle in single particle collision. Here,
      we demonstrate a well-defined 30 nm nanopore electrode with a rapid chemical
      electrochemical fabrication method which provides a high reproducibility in both
      size and performance. A capacitance-based detection mechanism is demonstrated to
      achieve a high current resolution of 0.6 pA +/-0.1 pA (RMS) and a high the
      temporal resolution of 0.01 ms. By utilizing this electrode, the dynamic
      interactions of every single particle in the mixture could be directly read
      during the collision process. The collision frequency is two orders of magnitude
      higher than previous reports, which helps reveal the hidden features of
      nanoparticles during the complex and multidimensional interaction processes.

PMID- 29210156
TI  - Selective Nascent Polymer Catch-and-Release Enables Scalable Isolation of Multi
      Kilobase Single-Stranded DNA.
AB  - Scalable methods currently are lacking for isolation of long ssDNA, an important
      material for numerous biotechnological applications. Conventional biomolecule
      purification strategies achieve target capture using solid supports, which are
      limited in scale and susceptible to contamination owing to nonspecific adsorption
      and desorption on the substrate surface. We herein disclose selective nascent
      polymer catch and release (SNAPCAR), a method that utilizes the reactivity of
      growing poly(acrylamide-co-acrylate) chains to capture acrylamide-labeled
      molecules in free solution. The copolymer acts as a stimuli-responsive anchor
      that can be precipitated on demand to pull down the target from solution. SNAPCAR
      enabled scalable isolation of multi-kilobase ssDNA with high purity and 50-70 %
      yield. The ssDNA products were used to fold various DNA origami. SNAPCAR-produced
      ssDNA will expand the scope of applications in nanotechnology, gene editing, and
      DNA library construction.

PMID- 29210157
TI  - Electronic Properties of h-BCN-Blue Phosphorene van der Waals Heterostructures.
AB  - Van der Waals heterostructures, a new class of materials made of a vertically
      selective assembly of various 2D monolayers held together by van der Waals
      forces, have attracted a great deal of attention due to their promise to deliver
      novel electronic and optoelectronic properties that are not achievable by using
      individual 2D crystals. Using density functional theory (DFT), it is revealed
      that van der Waals heterostructures composed of monolayers of hexagonal boron
      nitride (h-BN) and the latest P allotrope blue phosphorus (blue phosphorene,
      BlueP) forms a straddling type I band offset for which the band edges exclusively
      belong to BlueP. This feature enables h-BN to act as a protective coating
      material to resolve the air instability of BlueP. Furthermore, substitutional
      doping of C into h-BN (h-BCN) at a suitable concentration induces h-BCN-BlueP
      into staggered type II band offset. The type II band alignment triggered by the
      intensified built-in electric field across the sheets implies improved carrier
      mobility and the suppressed recombination of photogenerated hole pairs. These
      major benefits can pave the way for the potential functionality of h-BCN-BlueP to
      be exploited for efficient photovoltaic devices.

PMID- 29210158
TI  - Screening for human papillomavirus, cervical cytological abnormalities and
      associated risk factors in HIV-positive and HIV-negative women in Rwanda.
AB  - OBJECTIVES: Cervical cancer is the major cause of death from cancer in Africa. We
      wanted to assess the prevalence of human papillomavirus (HPV) infections and
      associated risk factors and to determine whether HPV testing could serve as a
      screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also
      wanted to obtain a broader understanding of the underlying risk factors for the
      establishment of HPV infection in Rwanda. METHODS: A total of 206 HIV-positive
      women, 172 HIV-negative women and 22 women with unknown HIV status were recruited
      at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in
      Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap
      test and a screening test analysing 37 HPV strains. RESULTS: Only 27% of HIV
      positive women and 7% of HIV-negative women had been screened for cervical cancer
      before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were
      more commonly infected with high-risk (HR) HPV and multitype HPV than HIV
      negative women. The sensitivity was 78% and the specificity 87% to detect high
      grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was
      positively associated with HR-HPV infection, while hepatitis B, Trichomonas
      vaginalis infection and HR-HPV infection were factors positively associated with
      SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection
      among HIV-positive women. HR-HPV infection and the number of live births were
      positively associated with SILs. CONCLUSIONS: The currently used quadrivalent
      vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV
      Screening may be effective to identify women at risk of developing cervical
      cancer, particularly if provided to high-risk patients.

PMID- 29210159
TI  - Safety of mTOR inhibitor continuation in pediatric heart transplant recipients
      undergoing surgical procedures.
AB  - mTOR inhibitors have been associated with SWC when used in the perioperative
      period. Limited literature is available to guide providers in managing chronic
      mTOR inhibitor use in the perioperative period, especially in the pediatric
      setting. The primary aim of this study was to describe the prevalence of SWC with
      mTOR inhibitor continuation during the perioperative period for major surgeries.
      Heart transplant recipients <=25 years old at the time of primary heart
      transplant receiving sirolimus maintenance therapy during a surgical procedure
      and within the study period were included. Surgeries identified within the study
      period included otolaryngology procedures (46.2%), such as tonsillectomies with
      or without adenoidectomies, cardiac surgeries (30.8%) including a sternal
      revision, pulmonary vein repair, and pacemaker placement in two patients,
      orthopedic surgeries (15.4%) including a posterior spinal fusion and an Achilles
      tendon lengthening with ankle and subtalar joint release, and a neurosurgery
      (7.7%), which was a ventriculoperitoneal shunt revision. Thirteen surgical
      encounters were examined. One SWC was observed, an infected pacemaker requiring
      systemic antibiotics and removal of the device. The results of this study suggest
      that sirolimus may be continued in the perioperative period based on the low rate
      of SWC observed.

PMID- 29210160
TI  - "Dumbbell"- and "Clackers"-Shaped Dimeric Derivatives of Monocarba-closo
      dodecaborate.
AB  - We designed, synthesized, and characterized two types of dimeric forms of
      monocarba-closo-dodecaborate, namely, a "dumbbell"-shaped dianion having a C-C
      bond and a "clackers"-shaped monoanion having an iodonium linker. The unique
      architectures of these anionic molecules were established by X-ray analysis.
      Spectroscopic analysis, DFT calculations, and reactivity experiments revealed
      high anionic and chemical stability of both anions, which are crucial properties
      for weakly coordinating anions.

PMID- 29210161
TI  - Do time of birth, unit volume, and staff seniority affect neonatal outcome in
      deliveries at >=34+0 weeks of gestation?
AB  - OBJECTIVE: We investigated whether time of birth, unit volume, and staff
      seniority affect neonatal outcome in neonates born at >=34+0 weeks of gestation.
      DESIGN: Population-based prospective cohort study. SETTING: Ten public hospitals
      in the Austrian province of Styria. SAMPLE: A total of 87 065 neonates delivered
      in the period 2004-2015. METHODS: Based on short-term outcome data, generalised
      linear mixed models were used to calculate the risk for adverse and severely
      adverse neonatal outcomes according to time of birth, unit volume, and staff
      seniority. MAIN OUTCOME MEASURES: Neonatal composite adverse and severely adverse
      outcome measures. RESULTS: The odds ratio for severely adverse events during the
      night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was
      1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant
      differences in neonatal outcome comparing weekdays and weekends, and comparing
      office hours and shifts. Units with 500-1000 deliveries per year had the lowest
      risk for adverse events. Adverse and severely adverse neonatal outcomes were
      least common for midwife-guided deliveries, and became more frequent with the
      level of experience of the doctors attending the delivery. With increasing
      pregnancy risks, senior staff attending delivery and delivering in a tertiary
      centre reduce the odds ratio for adverse events. CONCLUSIONS: Different times of
      delivery were associated with increased adverse neonatal outcomes. The management
      of uncomplicated deliveries by less experienced staff showed no negative impact
      on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff
      in a tertiary centre favour a better outcome. Achieving a better balance in the
      total number of labour ward staff during the day and the night appears to be a
      greater priority than increasing the continuous presence of senior obstetrical
      staff on the labour ward during the out-of-hours period. TWEETABLE ABSTRACT:
      Deliveries during night time lead to a greater number of neonates experiencing
      severely adverse events.

PMID- 29210162
TI  - Authors' reply re: Comparison of management regimens following ultrasound
      diagnosis of nontubal ectopic pregnancies: a retrospective cohort study.

PMID- 29210163
TI  - Author's reply re: Insight from outside BJOG. Research Snippets.

PMID- 29210164
TI  - Relative risk of home hemodialysis attrition in patients using a telehealth
      platform.
AB  - INTRODUCTION: Home hemodialysis (HHD) facilitates increased treatment frequency,
      which may improve patient outcomes. However, attrition due to technique failure
      limits the clinical effectiveness of the modality. Nx2me Connected Health is a
      telehealth platform that enables ongoing assessment of HHD patients using NxStage
      equipment, and that may reduce patient burden. We aimed to assess whether use of
      Nx2me was associated with risk of HHD attrition. METHODS: We compared risks of
      all-cause attrition, dialysis cessation (i.e., death or transplant), and
      technique failure in Nx2me users and matched control patients, using a
      retrospective cohort study. We also compared the likelihood of HHD training
      graduation in patients who initiated use of Nx2me during training with the
      likelihood in matched control patients. Matching factors included date of HHD
      initiation, NxStage treatment duration at initiation of follow-up, and prescribed
      treatment frequency. We used stratified Fine-Gray and Cox regression to compare
      risks, with adjustment for demographic factors and vascular access modality, and
      stratification by matched cluster. FINDINGS: We identified 606 Nx2me users; 49.5%
      initiated use of Nx2me in <3 months after initiation of HHD with NxStage
      equipment. Adjusted hazard ratios (AHRs) of all-cause attrition, dialysis
      cessation, and technique failure were 0.80 (95% confidence interval, 0.68-0.95),
      1.10 (0.86-1.41), and 0.71 (0.57-0.87), respectively, for Nx2me users vs. matched
      controls. AHRs were similar in patients who initiated use of Nx2me in <3 months
      after initiation of HHD. The AHR of HHD training graduation was 1.61 (1.10-2.36)
      in patients who initiated use of Nx2me within 2 weeks of training initiation vs.
      matched controls. DISCUSSION: Use of Nx2me was associated with lower risk of all
      cause attrition, lower risk of technique failure, and higher likelihood of HHD
      training graduation. Further studies are needed to identify the mechanisms by
      which use of a telehealth platform may improve clinical outcomes and reduce
      patient burden.

PMID- 29210165
TI  - Re: Maternal prepregnancy obesity and the risk of shoulder dystocia: a meta
      analysis.

PMID- 29210167
TI  - The Solid-Phase Synthesis of an Fe-N-C Electrocatalyst for High-Power Proton
      Exchange Membrane Fuel Cells.
AB  - The environmentally friendly synthesis of highly active Fe-N-C electrocatalysts
      for proton-exchange membrane fuel cells (PEMFCs) is desirable but remains
      challenging. A simple and scalable method is presented to fabricate FeII -doped
      ZIF-8, which can be further pyrolyzed into Fe-N-C with 3 wt % of Fe exclusively
      in Fe-N4 active moieties. Significantly, this Fe-N-C derived acidic PEMFC
      exhibits an unprecedented current density of 1.65 A cm-2 at 0.6 V and the highest
      power density of 1.14 W cm-2 compared with previously reported NPMCs. The
      excellent PEMFC performance can be attributed to the densely and atomically
      dispersed Fe-N4 active moieties on the small and uniform catalyst nanoparticles.

PMID- 29210166
TI  - Phytoceuticals in Fenugreek Ameliorate VLDL Overproduction and Insulin Resistance
      via the Insig Signaling Pathway.
AB  - SCOPE: This study aims to characterize the effect of fenugreek (Trigonella foenum
      graecum) seed and its phytoceutical trigonelline in antimetabolic inflammation
      and ameliorating overproduction of very low density lipoprotein (VLDL) in insulin
      resistance. METHODS AND RESULTS: Two groups of genetic hyperlipidemic mice
      generated by depletion of cAMP responsive element binding protein H (CREBH) are
      fed either a chow containing 2% fenugreek seed or vehicle for 7 weeks. Q-RT-PCR
      and immunoblotting analysis demonstrated that fenugreek seed containing diet
      inhibits hepatic SREBP-1c activation and the subsequent de novo lipogenesis by
      enhancing expression of insulin-inducible gene-1 (Insig-1) and gene-2 (Insig-2).
      mRNA expression of PPARalpha and its target genes that are involved in fatty acid
      beta-oxidation are also upregulated in the fenugreek seed fed-mice which is
      accompanied by significantly reduced hepatic lipid accumulation and VLDL
      secretion, improved endoplasmic reticulum (ER) stress, and ameliorated metabolic
      inflammation. These actions enhance insulin sensitivity and improve
      hyperlipidemia. In vitro, treating a rat hepatoma cell line, McA-RH7777 (McA),
      with trigonelline is able to recapitulate the results observed in vivo.
      CONCLUSIONS: This study unveils a novel mechanism of fenugreek seed and
      trigonelline in countering hepatic VLDL overproduction and insulin resistance by
      enhancing the Insig signaling pathways and ameliorating metabolic inflammatory
      stress in the liver.

PMID- 29210168
TI  - Effect of aorto-ventricular angulation on procedural success in transcatheter
      aortic valve replacements with the Lotus Valve system.
AB  - OBJECTIVE: To determine the effect of aorto-ventricular angulation (AA) on
      procedural success with the Lotus Valve system. BACKGROUND: AA, the angulation of
      the aortic valve basal plane, may affect the deployment of transcatheter aortic
      valve replacements (TAVRs). The Lotus Valve system is fully repositionable and
      delivered on a pre-shaped catheter which may alter the impact of AA on its
      deployment. The effect of AA on procedural and clinical outcomes with the Lotus
      valve is unreported. METHODS: Consecutive patients who underwent transfemoral
      TAVR with the Lotus Valve system were analyzed. AA was determined on pre
      procedural multi-detector computed tomography imaging. Device success, procedural
      characteristics, and clinical events were assessed according to Valve Academic
      Research Consortium-2 (VARC2) definitions. RESULTS: One hundred sixty-five
      patients were analyzed (48% male, mean age 84 years). The mean AA was 47.8
      degrees. Patients were, therefore, divided into low AA (AA < 48 degrees ) or high
      AA (AA >= 48 degrees ). Baseline characteristics were similar in both cohorts.
      Device success and procedural outcomes were also similar including procedure
      time, contrast dose, and need to reposition. There was no difference in degree of
      moderate or greater para-valvular regurgitation (PVR) (0% vs. 3%, P = 0.09).
      Clinical outcomes of death, stroke, myocardial infarction, and other major VARC2
      endpoints were similar. CONCLUSION: AA did not affect device success or clinical
      outcome with the Lotus Valve system. The Lotus' unique design features may have
      mitigated the impact of AA by improving the accuracy, ease of valve positioning,
      and reducing PVR.

PMID- 29210169
TI  - Electrospun nanofibers comprising of silk fibroin/gelatin for drug delivery
      applications: Thyme essential oil and doxycycline monohydrate release study.
AB  - In this study, a nanofibrous electrospun substrate based on the silk fibroin (SF)
      and gelatin (GT) polymers were prepared and evaluated. The SF/GT blended
      solutions were prepared with various ratios of GT in formic acid and electrospun
      to obtain bead-free fibers. Results showed that addition of GT to SF increased
      nanofiber's diameter, bulk hydrophilicity, surface wettability, mass loss
      percentage, but decreased Young's modulus, tensile strength, and porosity of the
      SF/GT mats. According to the obtained results, the mat containing 10% of GT was
      selected as the optimized mat for further studies and loaded with thyme essential
      oil (TEO) and doxycycline monohydrate (DCMH) as the antibacterial agents. Release
      studies showed a burst release of TEO from the mat within the first 3 h, while
      the DCMH had a sustained release during 48 h. In comparison to the TEO-loaded
      mat, the DCMH-loaded one showed larger inhibition zones against Staphylococcus
      aureus and Klebsiella pneumoniae bacteria. Meanwhile, cellular studies using
      mouse fibroblast L929 cells showed excellent cell-compatibility of TEO- and DCMH
      loaded mats. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      1092-1103, 2018.

PMID- 29210170
TI  - Erring on the side of education.

PMID- 29210171
TI  - A realist review of one-to-one breastfeeding peer support experiments conducted
      in developed country settings.
AB  - The World Health Organisation guidance recommends breastfeeding peer support
      (BFPS) as part of a strategy to improve breastfeeding rates. In the UK, BFPS is
      supported by National Institute for Health and Care Excellence guidance and a
      variety of models are in use. The experimental evidence for BFPS in developed
      countries is mixed and traditional methods of systematic review are ill-equipped
      to explore heterogeneity, complexity, and context influences on effectiveness.
      This review aimed to enhance learning from the experimental evidence base for one
      to-one BFPS intervention. Principles of realist review were applied to
      intervention case studies associated with published experimental studies. The
      review aimed (a) to explore heterogeneity in theoretical underpinnings and
      intervention design for one-to-one BFPS intervention; (b) inform design decisions
      by identifying transferable lessons developed from cross-case comparison of
      context-mechanism-outcome relationships; and (c) inform evaluation design by
      identifying context-mechanism-outcome relationships associated with experimental
      conditions. Findings highlighted poor attention to intervention theory and
      considerable heterogeneity in BFPS intervention design. Transferable mid-range
      theories to inform design emerged, which could be grouped into seven categories:
      (a) congruence with local infant feeding norms, (b) integration with the existing
      system of health care, (c) overcoming practical and emotional barriers to access,
      (d) ensuring friendly, competent, and proactive peers, (e) facilitating authentic
      peer-mother interactions, (f) motivating peers to ensure positive within
      intervention amplification, and (g) ensuring positive legacy and maintenance of
      gains. There is a need to integrate realist principles into evaluation design to
      improve our understanding of what forms of BFPS work, for whom and under what
      circumstances.

PMID- 29210172
TI  - Experience of dental care, knowledge and attitudes of older immigrants in Sweden
      A qualitative study.
AB  - OBJECTIVES: Knowledge about the oral health and dental care habits of older
      immigrants is limited. The aim of this study was to explore dental service
      utilization, oral care habits, and attitudes to and knowledge about oral diseases
      and their prevention among older immigrants in Sweden. METHODS: A qualitative
      research method was used, and data were collected in individual interviews to
      gain a deeper understanding of the immigrants' views. Thirteen immigrants, seven
      women and six men, recruited from meeting places for older immigrants,
      participated, all aged between 59 and 88 (median 72 years). Interviews were tape
      recorded and transcribed verbatim. Eight interviews were carried out with the
      help of an authorized interpreter. RESULTS: In the analytical process, performed
      using the content analysis method, meaning units were identified and condensed
      into codes which were labelled and grouped into subcategories and categories. The
      interview analysis resulted in four categories: Experiences of dental care,
      Attitudes, Barriers and Prevention of oral diseases. The elderly immigrants
      described a mix of regular and acute dental care and were often not satisfied
      with the outcome of the treatments. They stated that oral health was important
      and that they were responsible for their own teeth. Barriers to dental care were
      costs, language problems and lack of confidence in dental services. Daily oral
      hygiene routines were performed using a traditional chewing stick and/or regular
      toothbrush. CONCLUSION: The participants stated that, despite the barriers to
      treatment described above, they valued good oral health and visited dental
      services when they needed to.

PMID- 29210173
TI  - Direct and indirect approaches to identify drug modes of action.
AB  - Phenotypic assays are becoming increasingly more common among drug discovery
      practices, expanding drug target diversity as lead compounds identified through
      such screens are not limited to known targets. While increasing diversity is
      beneficial to the drug discovery process and the fight against disease, the
      unknown modes of action of new lead compounds can hamper drug discovery as, in
      most cases, the process of lead compound optimization is made difficult due to
      the unknown nature of the target; blindly changing substituents can prove
      fruitless due to the inexhaustible number of potential combinations, and it is
      therefore desirable to rapidly identify the targets of lead compounds developed
      through phenotypic screening. In addition, leads identified through target-based
      screening often have off-target effects that contribute towards drug toxicity,
      and by identifying those secondary targets, the drugs can be improved. However,
      the identification of a leads mode of action is far from trivial and now
      represents a major bottleneck in the drug discovery pipeline. This review looks
      at some of the recent developments in the identification of drug modes of action,
      focusing on phenotype-based methods using metabolomics, proteomics,
      transcriptomics, and genomics to detect changes in phenotype in response to the
      presence of the drug, and affinity-based methods using modified/unmodified drug
      as bait to capture and identify targets. (c) 2017 IUBMB Life, 70(1):9-22, 2018.

PMID- 29210174
TI  - Autophagy controls mesenchymal stem cell properties and senescence during bone
      aging.
AB  - Bone marrow-derived mesenchymal stem cells (BMMSCs) exhibit degenerative changes,
      including imbalanced differentiation and reduced proliferation during aging, that
      contribute to age-related bone loss. We demonstrate here that autophagy is
      significantly reduced in aged BMMSCs compared with young BMMSCs. The autophagy
      inhibitor 3-methyladenine (3-MA) could turn young BMMSCs into a relatively aged
      state by reducing their osteogenic differentiation and proliferation capacity and
      enhancing their adipogenic differentiation capacity. Accordingly, the autophagy
      activator rapamycin could restore the biological properties of aged BMMSCs by
      increasing osteogenic differentiation and proliferation capacity and decreasing
      adipogenic differentiation capacity. Possible underlying mechanisms were
      explored, and the analysis revealed that autophagy could affect reactive oxygen
      species and p53 levels, thus regulating biological properties of BMMSCs. In an in
      vivo study, we found that activation of autophagy restored bone loss in aged
      mice. In conclusion, our results suggest that autophagy plays a pivotal role in
      the aging of BMMSCs, and activation of autophagy could partially reverse this
      aging and may represent a potential therapeutic avenue to clinically treat age
      related bone loss.

PMID- 29210176
TI  - Online measurement of hemodialysis adequacy using effective ionic dialysance of
      sodium-a review of its principles, applications, benefits, and risks.
AB  - Dialysis dose is an important determinant of clinical outcomes in patients with
      end stage renal disease on maintenance dialysis. In clinical practice dialysis
      dose is monitored at least monthly by urea clearance based on Urea Kinetic
      Modeling. Online clearance monitoring using effective ionic dialysance (EID) of
      sodium (Na+ ) is available on some hemodialysis machines. This paper reviews the
      background, methodology, additional applications, and potential risks associated
      with EID. Effective ionic dialysance provides a reliable, real-time, noninvasive,
      and inexpensive measurement of dialysis dose during an ongoing hemodialysis (HD)
      session to allow interventions and assess the impact of these changes on
      clearance. Surveillance of vascular access flow rates can be used to screen for
      access dysfunction and refer for interventions. There is a concern that EID
      measurements may cause Na+ loading because of high dialysate Na+ used during
      these measurements, however, mathematical models, in vitro experiments, and
      clinical studies in patients on maintenance HD do not show any evidence of Na+
      loading during EID measurements. We cannot rule out the possibility of nonosmotic
      Na+ accumulation in the skin because no published literature exists on this topic
      as it pertains to clearance measurements based on EID of Na+ .

PMID- 29210175
TI  - Site-specific and endothelial-mediated dysfunction of the alveolar-capillary
      barrier in response to lipopolysaccharides.
AB  - Infectious agents such as lipopolysaccharides (LPS) challenge the functional
      properties of the alveolar-capillary barrier (ACB) in the lung. In this study, we
      analyse the site-specific effects of LPS on the ACB and reveal the effects on the
      individual cell types and the ACB as a functional unit. Monocultures of H441
      epithelial cells and co-cultures of H441 with endothelial cells cultured on
      Transwells(r) were treated with LPS from the apical or basolateral compartment.
      Barrier properties were analysed by the transepithelial electrical resistance
      (TEER), by transport assays, and immunostaining and assessment of tight
      junctional molecules at protein level. Furthermore, pro-inflammatory cytokines
      and immune-modulatory molecules were evaluated by ELISA and semiquantitative real
      time PCR. Liquid chromatography-mass spectrometry-based proteomics (LS-MS) was
      used to identify proteins and effector molecules secreted by endothelial cells in
      response to LPS. In co-cultures treated with LPS from the basolateral
      compartment, we noticed a significant reduction of TEER, increased permeability
      and induction of pro-inflammatory cytokines. Conversely, apical treatment did not
      affect the barrier. No changes were noticed in H441 monoculture upon LPS
      treatment. However, LPS resulted in an increased expression of pro-inflammatory
      cytokines such as IL-6 in OEC and in turn induced the reduction of TEER and an
      increase in SP-A expression in H441 monoculture, and H441/OEC co-cultures after
      LPS treatment from basolateral compartment. LS-MS-based proteomics revealed
      factors associated with LPS-mediated lung injury such as ICAM-1, VCAM-1,
      Angiopoietin 2, complement factors and cathepsin S, emphasizing the role of
      epithelial-endothelial crosstalk in the ACB in ALI/ARDS.

PMID- 29210177
TI  - Mitochondrial fission promotes cell migration by Ca2+ /CaMKII/ERK/FAK pathway in
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Mitochondrial dynamics of fission and fusion plays critical
      roles in a diverse range of important cellular functions, and its deregulation
      has been increasingly implicated in human diseases. Previous studies have shown
      that increased mitochondrial fission significantly promoted the proliferation of
      hepatocellular carcinoma (HCC) cells. However, how they influence the migration
      of tumour cells remained largely unknown. METHODS: In the present study, we
      further investigated the effect of mitochondrial fission on the migration and
      metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular
      mechanisms and therapeutic application were explored. RESULTS: Our data showed
      that dynamin-1-like protein expression was strongly increased in distant
      metastasis of hepatocellular carcinoma when compared to primary hepatocellular
      carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an
      opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin
      1 was significantly associated with the disease-free survival of hepatocellular
      carcinoma patients. In addition, our data further showed that mitochondrial
      fission significantly promoted the reprogramming of focal-adhesion dynamics and
      lamellipodia formation in hepatocellular carcinoma cells mainly by activating
      typical Ca2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial
      division inhibitor-1 significantly decreased calcium signalling in hepatocellular
      carcinoma cells and had a potential treatment effect for hepatocellular carcinoma
      metastasis in vivo. CONCLUSIONS: Taken together, our findings demonstrate that
      mitochondrial fission plays a critical role in the regulation of hepatocellular
      carcinoma cell migration, which provides strong evidence for this process as a
      drug target in hepatocellular carcinoma metastasis treatment.

PMID- 29210178
TI  - Acute exposure to high-induction electromagnetic field affects activity of model
      peripheral sensory neurons.
AB  - Exposure to repetitive low-frequency electromagnetic field (LF-EMF) shows promise
      as a non-invasive approach to treat various sensory and neurological disorders.
      Despite considerable progress in the development of modern stimulation devices,
      there is a limited understanding of the mechanisms underlying their biological
      effects and potential targets at the cellular level. A significant impact of
      electromagnetic field on voltage-gated calcium channels and downstream signalling
      pathways has been convincingly demonstrated in many distinct cell types. However,
      evidence for clear effects on primary sensory neurons that particularly may be
      responsible for the analgesic actions of LF-EMF is still lacking. Here, we used
      F11 cells derived from dorsal root ganglia neurons as an in vitro model of
      peripheral sensory neurons and three different protocols of high-induction
      magnetic stimulation to determine the effects on chemical responsiveness and
      spontaneous activity. We show that short-term (<180 sec.) exposure of F11 cells
      to LF-EMF reduces calcium transients in response to bradykinin, a potent pain
      producing inflammatory agent formed at sites of injury. Moreover, we characterize
      an immediate and reversible potentiating effect of LF-EMF on neuronal spontaneous
      activity. Our results provide new evidence that electromagnetic field may
      directly modulate the activity of sensory neurons and highlight the potential of
      sensory neuron-derived cell line as a tool for studying the underlying mechanisms
      at the cellular and molecular level.

PMID- 29210179
TI  - Cross-sectional follow-up of voice outcomes in children who have a history of
      airway reconstruction surgery.
AB  - OBJECTIVES: This study reports vocal function in a cross-section of children with
      subglottic stenosis. Each child had a history of laryngotracheal reconstruction
      and/or cricotracheal resection surgery. Vocal function was measured using
      laryngoscopy, acoustic analysis, perceptual evaluation and impact of voice on
      quality of life. DESIGN: All patients aged >5 years with history of
      laryngotracheal reconstruction and/or cricotracheal resection surgery at the
      Scottish National Complex Airways service were invited to participate. SETTING:
      Data were gathered in the Royal Hospital for Children in Glasgow in a single
      outpatient appointment. PARTICIPANTS: Twelve of 56 former patients (aged 5-27)
      provided a voice sample and eleven consented to awake laryngoscopy. All consented
      for detailed evaluation of their medical records. MAIN OUTCOME MEASURES: Acoustic
      analysis of fundamental frequency and pitch perturbation was conducted on
      sustained vowel [a]. Perceptual evaluation was conducted by 4 trained listeners
      on a series of spoken sentences. Impact on quality of life was measured using the
      paediatric voice-related quality of life questionnaire. Laryngeal function was
      descriptively evaluated. RESULTS: Four children had normal voice acoustically,
      perceptually and in relation to voice-related quality of life. One of these had
      vocal fold nodules unrelated to surgical history. Two other children had "near
      normal" vocal function, defined where most voice measurements fell within the
      normal range. CONCLUSIONS: Normal or "near normal" voice is a possible outcome
      for children who have had this surgery. Where there is an ongoing complex medical
      condition, voice outcome may be poorer.

PMID- 29210180
TI  - Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin
      through their D-domains, contributing to platelet adhesion and activation during
      thrombus formation.
AB  - : Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and
      fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized
      fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer
      may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin
      interaction supports spreading, activation and adhesion involving alphaIIbbeta3.
      SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds
      collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin.
      Objectives To determine if GPVI-dimer, GPVI-monomer, or both bind to fibrinogen
      substrates, and which region common to these substrates contains the interaction
      site. Methods Recombinant GPVI monomeric extracellular domain (GPVIex ) or
      dimeric Fc-fusion protein (GPVI-Fc2 ) binding to immobilized fibrinogen
      derivatives was measured by ELISA, including competition assays involving
      collagenous substrates and fibrinogen derivatives. Flow adhesion was performed
      with normal or Glanzmann thrombasthenic (GT) platelets over immobilized
      fibrinogen, with or without anti-GPVI-dimer or anti-alphaIIbbeta3. Results Under
      static conditions, GPVIex did not bind to any fibrinogen substrate. GPVI-Fc2
      exhibited specific, saturable binding to both D-fragment and D-dimer, which was
      inhibited by mFab-F (anti-GPVI-dimer), but showed low binding to fibrinogen and
      fibrin under our conditions. GPVI-Fc2 binding to D-fragment or D-dimer was
      abrogated by collagen type III, Horm collagen or CRP-XL (crosslinked collagen
      related peptide), suggesting proximity between the D-domain and collagen binding
      sites on GPVI-dimer. Under low shear, adhesion of normal platelets to D-fragment,
      D-dimer, fibrinogen and fibrin was inhibited by mFab-F (inhibitor of GPVI-dimer)
      and abolished by Eptifibatide (inhibitor of alphaIIbbeta3), suggesting that both
      receptors contribute to thrombus formation on these substrates, but alphaIIbbeta3
      makes a greater contribution. Notably, thrombasthenic platelets showed limited
      adhesion to fibrinogen substrates under flow, which was further reduced by mFab
      F, supporting some independent GPVI-dimer involvement in this interaction.
      Conclusion Only dimeric GPVI interacts with fibrinogen D-domain, at a site
      proximate to its collagen binding site, to support platelet
      adhesion/activation/aggregate formation on immobilized fibrinogen and polymerized
      fibrin.

PMID- 29210181
TI  - Intraoral versus extraoral cementation of implant-supported single crowns:
      Clinical, biomarker, and microbiological comparisons.
AB  - OBJECTIVES: Implant supported single metal-ceramic crowns cemented either
      extraorally or intraorally were comparatively evaluated by clinical, radiologic,
      biomarker, and microbiological parameters. MATERIALS AND METHODS: Twelve patients
      with bilateral single tooth gap in the maxillary posterior region received two
      locking-taper implants; 4.5 mm width, 8 mm length. Selection of intraoral (IOC)
      or extraoral cementation (EOC) using screwless titanium abutments was done
      randomly. Peri-implant crevicular fluid (PICF), gingival crevicular fluid (GCF)
      samples were collected from the implants, adjacent teeth, and bleeding on
      probing, soft tissue thickness, keratinized tissue width were recorded before
      starting the prosthetic procedures (baseline) and 3, 6 months after implant
      loading. Crestal bone loss was measured on radiographs taken immediately and 6
      months after cementation. Cytokine levels, amounts of bacteria were determined in
      PICF/GCF samples. Data were tested by appropriate statistical analyses. RESULTS:
      Clinical findings were similar in the crowns cemented extraorally or intraorally
      at all times (P < .05). PICF and GCF data were similar. At 3 month, interleukin
      17E and osteoprotegerin levels were lower in the intraorally cemented crowns.
      CONCLUSION: Extraorally and intraorally cemented crowns exhibited similar crestal
      bone loss after loading. Higher amount of osteoprotegerin at 3 month at the EOC
      than the IOC sites might bode well for good osseointegration.

PMID- 29210182
TI  - Topical ofloxacin use in glucose-6-phosphate dehydrogenase deficiency-safe or
      unsafe?

PMID- 29210184
TI  - Sympathetic nerve activity and neuro-inflammation: Who is in the driver's seat?

PMID- 29210183
TI  - Young plasma reverses age-dependent alterations in hepatic function through the
      restoration of autophagy.
AB  - Recent studies showing the therapeutic effect of young blood on aging-associated
      deterioration of organs point to young blood as the solution for clinical
      problems related to old age. Given that defective autophagy has been implicated
      in aging and aging-associated organ injuries, this study was designed to
      determine the effect of young blood on aging-induced alterations in hepatic
      function and underlying mechanisms, with a focus on autophagy. Aged rats (22
      months) were treated with pooled plasma (1 ml, intravenously) collected from
      young (3 months) or aged rats three times per week for 4 weeks, and 3
      methyladenine or wortmannin was used to inhibit young blood-induced autophagy.
      Aging was associated with elevated levels of alanine transaminase and aspartate
      aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective
      liver regeneration after partial hepatectomy, which were significantly attenuated
      by young plasma injections. Young plasma could also restore aging-impaired
      autophagy activity. Inhibition of the young plasma-restored autophagic activity
      abrogated the beneficial effect of young plasma against hepatic injury with
      aging. In vitro, young serum could protect old hepatocytes from senescence, and
      the antisenescence effect of young serum was abrogated by 3-methyladenine,
      wortmannin, or small interfering RNA to autophagy-related protein 7.
      Collectively, our data indicate that young plasma could ameliorate age-dependent
      alterations in hepatic function partially via the restoration of autophagy.

PMID- 29210186
TI  - A retrospective study on clinical and radiological outcomes of oral implants in
      patients followed up for a minimum of 20 years.
AB  - BACKGROUND: Very long-term follow-up of oral implants is seldom reported in the
      literature. PURPOSE: To assess oral implant failure rates and marginal bone loss
      (MBL) of patients followed up for a minimum of 20 years. MATERIALS AND METHODS:
      Implants placed in patients followed up for 20+ years were included. Descriptive
      statistics, survival analyses, generalized estimating equations were performed.
      Three-hundred implants were randomly selected for MBL. RESULTS: 1,045 implants
      (227 patients) were included. Implant location, irradiation, and bruxism affected
      the implant survival rate. Thirty-five percent of the failures occurred within
      the first year after implantation, and another 26.8% in the second/third year.
      There was a cumulative survival rate of 87.8% after 36 years of follow-up. In the
      last radiological follow up, 35 implants (11.7%) had bone gain, and 35 implants
      (11.7%) presented at least 3 mm of MBL. Twenty-six out of 86 failed implants with
      available radiograms presented severe MBL in the last radiological register
      before implant failure. CONCLUSIONS: Most of the implant failures occurred at the
      first few years after implantation, regardless of a very long follow up. MBL can
      be insignificant in long-term observations, but it may, nevertheless, be the
      cause of secondary failure of oral implants in some cases.

PMID- 29210185
TI  - Redemption of the "spoiled identity:" the role of HIV-positive individuals in HIV
      care cascade interventions.
AB  - INTRODUCTION: The concept of "therapeutic citizenship" has drawn attention to
      ways in which public testimony, the "story-telling in the public sphere"
      undertaken by people living with HIV (PLHIV), has shaped the global response to
      the epidemic. This paper presents qualitative findings from two large studies in
      eastern Africa that reveal how the advent of population-based HIV testing
      campaigns and efforts to accelerate antiretroviral "treatment for all" has
      precipitated a rapidly expanding therapeutic citizenship "project," or social
      movement. The title of this paper refers to Goffman's original conceptualization
      of stigma as a social process through which a person's identity is rendered
      "spoiled." METHODS: Data were derived from qualitative studies embedded within
      two clinical trials, Sustainable East African Research in Community Health
      (SEARCH) (NCT# 01864603) in Kenya and Uganda, and START-ART (NCT# 01810289) in
      Uganda, which aimed to offer insights into the pathways through which outcomes
      across the HIV care continuum can be achieved by interventions deployed in the
      studies, any unanticipated consequences, and factors that influenced
      implementation. Qualitative in-depth semi-structured interviews were conducted
      among cohorts of adults in 2014 through 2015; across both studies and time
      periods, 217 interviews were conducted with 166 individuals. Theoretically
      informed, team-based analytic approaches were used for the analyses. RESULTS:
      Narratives from PLHIV, who have not always been conceptualized as actors but
      rather usually as targets of HIV interventions, revealed strongly emergent themes
      related to these individuals' use of HIV biomedical resources and discourses to
      fashion a new, empowered subjecthood. Experiencing the benefits of antiretroviral
      therapy (ART) emboldens many individuals to transform their "spoiled" identities
      to attain new, valorized identities as "advocates for ART" in their communities.
      We propose that the personal revelation of what some refer to as the "gospel of
      ARVs," the telling of personal stories about HIV in the public sphere and actions
      to accompany other PLHIV on their journey into care, is driven by its power to
      redeem the "spoiled identity:" it permits PLHIV to overcome self-stigma and
      regain full personhood within their communities. CONCLUSIONS: PLHIV are playing
      an unanticipated but vital role in the successful implementation of HIV care
      cascade interventions.

PMID- 29210187
TI  - Re: Starting a uterus transplantation service: notes from a small island.

PMID- 29210188
TI  - Factors influencing the fracture of dental implants.
AB  - BACKGROUND: Implant fractures are rare but offer a challenging clinical
      situation. PURPOSE: To determine the prevalence of implant fracture and the
      possible risk factors predisposing an implant to a higher fracture risk.
      MATERIALS AND METHODS: This retrospective study is based on 2670 patients
      consecutively treated with implant-supported prostheses. Anatomical-, patient-,
      and implant-related factors were collected. Descriptive statistics and survival
      analyses were performed. Generalized estimating equations (GEE) evaluated the
      effect of explanatory variables on implant fracture. RESULTS: Forty-four implants
      (out of 10 099; 0.44%) fractured. The mean +/- standard deviation time for
      fracture to occur was 95.1 +/- 58.5 months (min-max, 3.8-294.7). Half of the
      occurrences of fracture happened between 2 and 8 years after implantation. Five
      factors had a statistically significant influence on the fracture of implants
      (increase/decrease in fracture probability): use of higher grades of titanium
      (decrease 72.9%), bruxism (increase 1819.5%), direct adjacency to cantilever
      (increase 247.6%), every 1 mm increase in implant length (increase 22.3%), every
      1 mm increase in implant diameter (decrease 96.9%). CONCLUSIONS: It is suggested
      that 5 factors could influence the incidence of implant fractures: grade of
      titanium, implant diameter and length, cantilever, bruxism.

PMID- 29210190
TI  - Manipulating the cell/air space ratio to optimize photosynthesis.

PMID- 29210189
TI  - Does mean arterial blood pressure scale with body mass in mammals? Effects of
      measurement of blood pressure.
AB  - For at least the last 30 years, it has been discussed whether mean arterial blood
      pressure (MAP) is independent of body mass or whether it increases in accordance
      with the vertical height between the heart and the brain. The debate has centred
      on the most appropriate mathematical models for analysing allometric scaling and
      phylogenetic relationships; there has been previously little focus on evaluating
      the validity of underlying physiological data. Currently, the 2 most
      comprehensive scaling analyses are based on data from 47 species of mammals,
      based on 114 references. We reviewed all available references to determine under
      which physiological conditions MAP had been recorded. In 44 (38.6%) of the cited
      references, MAP was measured in anaesthetized animals. Data from conscious
      animals were reported in 59 (51.8%) of references; of these, 3 (2.6%) were
      radiotelemetric studies. In 5 species, data were reported from both anaesthetized
      and conscious animals, and the mean difference in the MAP between these settings
      was 20 +/- 29 mm Hg. From a literature search, we identified MAP measurements
      performed by radiotelemetry in 11 of the 47 species included in the meta
      analyses. A Bland-Altman analysis showed a bias of 1 mm Hg with 95% confidence
      interval (from -35 to 36 mm Hg); that is, the limits of agreement between
      radiotelemetric studies and studies in restrained animals were double the
      supposed difference in the MAP between the mouse and elephant. In conclusion, the
      existing literature does not provide evidence for either a positive or neutral
      scaling of arterial pressure to body mass across taxa.

PMID- 29210192
TI  - Correction.

PMID- 29210191
TI  - Correction.

PMID- 29210193
TI  - Islet damage during isolation as assessed by miRNAs and the correlation of miRNA
      levels with posttransplantation outcome in islet autotransplantation.
AB  - High-quality pancreatic islets are essential for better posttransplantation
      endocrine function in total pancreatectomy with islet autotransplantation
      (TPIAT), yet stress during the isolation process affects quality and yield. We
      analyzed islet-enriched microRNAs (miRNAs) -375 and -200c released during
      isolation to assess damage and correlated the data with posttransplantation
      endocrine function. The absolute concentration of miR-375, miR-200c, and C
      peptide was measured in various islet isolation steps, including digestion,
      dilution, recombination, purification, and bagging, in 12 cases of TPIAT.
      Posttransplantation glycemic control was monitored through C-peptide, hemoglobin
      A1c , insulin requirement, and SUITO index. The amount of miR-375 released was
      significantly higher during enzymatic digestion followed by the islet bagging (P
      < .001). Mir-200c mirrored these changes, albeit at lower concentrations. In
      contrast, the C-peptide amount was significantly higher in the purification and
      bagging steps (P < .001). Lower amounts of miR-375 were associated with a lower 6
      month insulin requirement (P = .01) and lower hemoglobin A1c (P = .04).
      Measurement of the absolute quantity of miRNA-375 and -200c released during islet
      isolation is a useful tool to assess islet damage. The quantity of released miRNA
      is indicative of posttransplantation endocrine function in TPIAT patients.

PMID- 29210194
TI  - Error-related brain activity and anxiety symptoms in youth with autism spectrum
      disorder.
AB  - : Individuals with autism spectrum disorder (ASD) often experience symptoms
      associated with generalized anxiety disorder, obsessive-compulsive disorder, and
      social anxiety disorder. In other populations, these same symptoms are associated
      with a larger error-related negativity (ERN), an event-related potential that
      reflects endogenous threat sensitivity. As such, it is possible that the ERN may
      relate to the clinical presentation of anxiety in ASD. However, studies examining
      these associations in youth with ASD have yielded mixed results. The present
      study aimed to clarify this relationship by examining the ERN in relation to
      these specific anxiety symptoms in ASD, and by accounting for typical covariates
      (e.g., age, verbal abilities, depression, ASD symptoms) of the ERN. Fifty-one
      youth, ages 8-17, with ASD and intact cognitive ability completed a modified
      Flanker task, from which the ERN component was obtained. Measures of anxiety,
      verbal abilities, depression, and ASD symptoms were collected from participants
      and parents. Results revealed that greater self-reported social anxiety symptoms,
      specifically performance fears but not humiliation/rejection fears, were
      associated with an increased neural response to errors, as measured by the ERN.
      This relationship remained after controlling for other anxiety symptoms, as well
      as age, verbal IQ, depression symptoms, and ASD symptoms. Findings suggest that
      heightened threat sensitivity may be characteristic of individuals with ASD who
      exhibit social fearfulness. Autism Res 2018, 11: 342-354. (c) 2017 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The error
      related negativity (ERN) is a physiological measure of the brain's response to
      errors which is thought to reflect threat sensitivity and has been implicated in
      anxiety disorders in individuals without autism spectrum disorder (ASD). The
      present study revealed that the ERN is related to social anxiety symptoms,
      specifically performance fears, in a sample of youth with ASD. Findings suggest
      that heightened threat sensitivity may be characteristic of individuals with ASD
      who exhibit social fearfulness.

PMID- 29210195
TI  - Hair nicotine at 15 months old, tobacco exposure and wheeze or asthma from 15
      months to 6 years old.
AB  - OBJECTIVE: To investigate the relationship between hair nicotine levels at 15
      months of age and prior parent-reported smoking exposure, and the risk of
      wheezing and current asthma from 15 months to 6 years of age. STUDY DESIGN: We
      measured hair nicotine levels at 15 months of age in 376 of 535 infants enrolled
      in a prospective birth cohort in Christchurch, New Zealand. We obtained detailed
      information from parents about smoking exposure during pregnancy and in the home
      at 3 and 15 months of age. Data for demographics, wheezing, and asthma were
      obtained from yearly questionnaires up to age 6 years. We assessed hair nicotine
      levels in relation to reported smoke exposure in pregnancy and up to age 15
      months, and the association between high levels of hair nicotine and annual
      reports of current wheeze and current asthma using multiple logistic regression.
      RESULTS: Hair nicotine increased with numbers of smokers and daily cigarettes
      smoked at home, and was also strongly associated with smoking in pregnancy. High
      level of hair nicotine was associated with increased risk of wheeze (Odds ratio
      2.30, P = 0.001) and, though not significant, of current asthma (Odds ratio 2.02,
      P = 0.056) at 15 months of age, after controlling for socio-economic status,
      ethnicity, body mass index, respiratory infections in the first 3 months of life,
      and duration of exclusive breastfeeding. At older ages the associations were non
      significant. CONCLUSION: In children aged 15 months hair nicotine level was
      related to smoking exposure, and was associated with increased risk of wheeze and
      asthma.

PMID- 29210196
TI  - Ultrasonographic detection of double contour sign and hyperechoic aggregates for
      diagnosis of gout: two sites examination is as good as six sites examination.
AB  - OBJECTIVE: To compare ultrasound-detected abnormalities, namely double contour
      sign (DCS) and hyperechoic aggregates (HAGs), at two sites (knee and first
      metatarsophalangeal [1st MTP] joints) versus six sites (knee joint, 1st MTP
      joint, radiocarpal joint, talar joint, patellar tendon and triceps tendon) in
      gout patients. METHODS: Forty-seven clinically diagnosed gout patients and 50
      subjects (serum uric acid < 7 mg/dL) as controls were included. DCS was looked
      for at three articular cartilage sites (first metatarsal, tibiotalar and femoral
      condyle), whereas HAGs were looked for at one joint site (radiocarpal joint) and
      two tendon sites (patellar tendon and triceps tendon). Ultrasound findings of
      both the groups were compared. RESULTS: Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and positive likelihood
      ratio (LR) of two sites ultrasound findings for gout were 87.2%, 84%, 83.7%,
      85.6% and 5.5 respectively. Similar sensitivity, specificity, PPV, NPV and
      positive LR were observed with six sites ultrasound findings. Among controls, 16%
      were found to have these abnormal ultrasound findings by both two sites and six
      sites examinations. CONCLUSION: Screening of two sites (knee and 1st MTP) has
      similar sensitivity, specificity, PPV, NPV and positive LR as compared to six
      sites in diagnosing gout.

PMID- 29210197
TI  - Calpain-2 inhibitor treatment preferentially reduces tumor progression for human
      colon cancer cells expressing highest levels of this enzyme.
AB  - Calpain-2 levels are higher in colorectal tumors resistant to chemotherapy and
      previous work showed calpain-2 inhibitor therapy reduced inflammation-driven
      colorectal cancer, but direct effects of the inhibitor on colon cancer cells
      themselves were not demonstrated. In the present study, five human colon cancer
      cell lines were directly treated with a calpain-2 inhibitor and results showed
      increased cell death in 4 of 5 cell lines and decreased anchorage-independent
      growth for all cell five lines. When tested for levels of calpain-2, three cell
      lines exhibited increasing levels of this enzyme: HCT15 (low), HCC2998 (medium),
      and HCT116 (significantly higher). This was consistent with gel shift assays
      showing that calpain-2 inhibitor reduced of NF-kappaB nuclear translocation most
      effectively in HCT116 cells. Ability of calpain-2 inhibitor to impede tumor
      progression in vivo was evaluated using intrarectal transplant of luciferase
      expressing cells for these three cell lines. Results showed that calpain-2
      inhibitor therapy reduced tumor growth and increased survival only in mice
      injected with HCT116 cells. These data suggest calpain-2 inhibitor treatment may
      be most effective on colorectal tumors expressing highest levels of calpain-2.

PMID- 29210199
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 50/2017.

PMID- 29210200
TI  - Usefulness of indocyanine green fluorescence imaging: A case of laparoscopic
      distal gastrectomy after distal pancreatectomy with splenectomy.
AB  - Safe preservation of the remnant stomach during distal gastrectomy in patients
      who have undergone distal pancreatectomy is important. During distal
      pancreatectomy, the splenic artery that supplies arterial blood to the cardiac
      part of stomach is resected. Previous reports suggested that blood flow to the
      remnant stomach may be insufficient when supplied by only the left inferior
      phrenic artery. In the present case, a 79-year-old woman who underwent distal
      pancreatectomy with splenectomy 20 years before she was diagnosed with gastric
      cancer and referred to our hospital. We performed laparoscopic distal gastrectomy
      and Roux-en-Y reconstruction because preoperative CT scan indicated a developed
      left inferior phrenic artery. To evaluate the blood supply, we employed
      indocyanine green fluorescence and were able to safely preserve the remnant
      stomach. Our experience suggests that indocyanine green fluorescence is
      potentially useful for evaluating blood flow to the remnant stomach.

PMID- 29210198
TI  - Concise Review: Quantitative Detection and Modeling the In Vivo Kinetics of
      Therapeutic Mesenchymal Stem/Stromal Cells.
AB  - Mesenchymal stem/stromal cells (MSCs) present a promising tool in cell-based
      therapy for treatment of various diseases. Currently, optimization of treatment
      protocols in clinical studies is complicated by the variations in cell dosing,
      diverse methods used to deliver MSCs, and the variety of methods used for
      tracking MSCs in vivo. Most studies use a dose escalation approach, and attempt
      to correlate efficacy with total cell dose. Optimization could be accelerated
      through specific understanding of MSC distribution in vivo, long-term viability,
      as well as their biological fate. While it is not possible to quantitatively
      detect MSCs in most targeted organs over long time periods after systemic
      administration in clinical trials, it is increasingly possible to apply
      pharmacokinetic modeling to predict their distribution and persistence. This
      Review outlines current understanding of the in vivo kinetics of exogenously
      administered MSCs, provides a critical analysis of the methods used for
      quantitative MSC detection in these studies, and discusses the application of
      pharmacokinetic modeling to these data. Finally, we provide insights on and
      perspectives for future development of effective therapeutic strategies using
      pharmacokinetic modeling to maximize MSC therapy and minimize potential side
      effects. Stem Cells Translational Medicine 2018;7:78-86.

PMID- 29210201
TI  - Maxillary artery 18F-FDG uptake as a new finding on PET/CT scan in a cohort of 41
      patients suspected of having giant cell arteritis.

PMID- 29210202
TI  - Amount or intensity? Potential targets of exercise interventions in patients with
      heart failure with preserved ejection fraction.
AB  - AIMS: Heart failure with preserved ejection fraction (HFpEF) remains a common
      condition with no pharmacological treatment. Physical activity (PA) improves
      symptoms and quality of life (QoL), but no clear recommendations exist on PA in
      HFpEF patients. We investigated the association of PA (amount/intensity) on
      clinical phenotype in HFpEF. METHODS AND RESULTS: The Aldosterone in Diastolic
      Heart Failure trial investigated spironolactone vs. placebo in stable HFpEF
      patients. At baseline, all patients underwent detailed phenotypization including
      echocardiography, cardiopulmonary exercise testing, 6 minute walking test (6MWT),
      and QoL assessment (36-item Short-Form questionnaire). PA was assessed by a self
      report questionnaire, classified in metabolic equivalents of task (MET) and
      analysed with regard to exercise capacity, diastolic function, and QoL. Four
      hundred twenty-two patients (52% women, age 67 +/- 8 years, New York Heart
      Association II and III) were classified by weekly MET hours into a low (<70),
      middle (70-140), or high (>140) level of PA. Total PA correlated positively with
      6MWT distance (r = 0.17; P = 0.002) and physical function of QoL (r = 0.10; P =
      0.05), but not with peak oxygen uptake (peakVO2 ). In contrast, both 6MWT
      distance and peakVO2 were significantly higher in patients who performed high
      intensity PA for >8 h/week (P < 0.001, P = 0.02, respectively). Time of high
      intensity PA was related to higher 6MWT distance (r = 0.21, P < 0.001), peakVO2 ,
      and better physical function of QoL (both r = 0.13, P = 0.01), whereas low
      intensity PA did not show significant associations. Interestingly, PA was not
      related to any measure of diastolic function. CONCLUSIONS: A higher amount of PA
      is related to higher submaximal exercise capacity and physical function of QoL.
      Regarding maximal exercise capacity, only high-intensity PA showed significant
      association in HFpEF patients.

PMID- 29210204
TI  - Validation and reliability of the Timed Up and Go test for measuring objective
      functional impairment in patients with long-standing rheumatoid arthritis: a
      cross-sectional study.
AB  - AIM: This study aimed to validate the Timed Up and Go test (TUG) for measuring
      objective functional impairment in patients with established rheumatoid arthritis
      (RA) based on a prospective observational cohort of RA patients undergoing joint
      surgery. METHODS: We collected data on demographics, Health Assessment
      Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI
      and other patient-reported outcomes, including European Quality of life scale (EQ
      5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI <=0.5),
      normal HAQ (HAQ-DI <=0.25), and the absence of disability in each HAQ-DI category
      were also determined by age. RESULTS: A total of 435 patients were enrolled and
      analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ
      DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with
      aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising,
      walking, reach and activity). After adjusting for age and sex, mean TUG values
      were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4
      10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were
      7.2 sec (5.9-8.5) in young patients (<=61 years), 9.1 sec (7.6-10.5) in middle
      aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (>=71 years).
      CONCLUSION: TUG was significantly associated with functional impairment and aging
      in patients with long-standing RA. Thus, TUG could be useful in setting treatment
      goals for joint surgery and rehabilitation in established RA patients.

PMID- 29210203
TI  - The effects of the attributable fraction and the duration of symptoms on burden
      estimates of influenza-associated respiratory illnesses in a high HIV prevalence
      setting, South Africa, 2013-2015.
AB  - BACKGROUND: The attributable fraction of influenza virus detection to illness
      (INF-AF) and the duration of symptoms as a surveillance inclusion criterion could
      potentially have substantial effects on influenza disease burden estimates.
      METHODS: We estimated rates of influenza-associated influenza-like illness (ILI)
      and severe acute (SARI-10) or chronic (SCRI-10) respiratory illness (using a
      symptom duration cutoff of <=10 days) among HIV-infected and HIV-uninfected
      patients attending 3 hospitals and 2 affiliated clinics in South Africa during
      2013-2015. We calculated the unadjusted and INF-AF-adjusted rates and relative
      risk (RR) due to HIV infection. Rates were expressed per 100 000 population.
      RESULTS: The estimated mean annual unadjusted rates of influenza-associated
      illness were 1467.7, 50.3, and 27.4 among patients with ILI, SARI-10, and SCRI
      10, respectively. After adjusting for the INF-AF, the percent reduction in the
      estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8), and 16.3% (rate:
      22.9) among patients with ILI, SARI-10, and SCRI-10, respectively. HIV-infected
      compared to HIV-uninfected individuals experienced a 2.3 (95% CI: 2.2-2.4)-, 9.7
      (95% CI: 8.0-11.8)-, and 10.0 (95% CI: 7.9-12.7)-fold increased risk of influenza
      associated illness among patients with ILI, SARI-10, and SCRI-10, respectively.
      Overall 34% of the estimated influenza-associated hospitalizations had symptom
      duration of >10 days; 8% and 44% among individuals aged <5 and >=5 years,
      respectively. CONCLUSION: The marginal differences between unadjusted and INF-AF
      adjusted rates are unlikely to affect policies on prioritization of
      interventions. HIV-infected individuals experienced an increased risk of
      influenza-associated illness and may benefit more from annual influenza
      immunization. The use of a symptom duration cutoff of <=10 days may underestimate
      influenza-associated disease burden, especially in older individuals.

PMID- 29210205
TI  - Cobalt Nanoparticles Supported on Nitrogen-Doped Carbon: An Effective Non-Noble
      Metal Catalyst for the Upgrade of Biofuels.
AB  - A new method has been developed for the deoxygenation of vanillin to produce 2
      methoxy-4-methylphenol (MMP) as a promising liquid fuel over a heterogeneous non
      noble metal catalyst. Cobalt nanoparticles supported on nitrogen-doped carbon
      (Co/N-C-600) exhibit high activity and stability for the deoxygenation of
      vanillin into MMP under mild conditions (150  degrees C, 10 bar H2 ). Nearly
      quantitative MMP yield is obtained in isopropanol after 8 h at 150  degrees C and
      10 bar H2 pressure. According to the distribution of products with time, the
      deoxygenation of vanillin into MMP mainly proceeds through the hydrogenation of
      vanillin into vanillyl alcohol and the subsequent hydrogenolysis of vanillyl
      alcohol into MMP, of which the latter is the rate-determining step, owing to a
      much higher activation energy. Moreover, after being recycled several times, the
      loss of catalytic activity is negligible, which demonstrates that the Co/N-C-600
      catalyst shows good resistance to deactivation.

PMID- 29210206
TI  - Intra-articular platelet-rich plasma injections for knee osteoarthritis: An
      overview of systematic reviews and risk of bias considerations.
AB  - OBJECTIVES: Numerous systematic reviews investigating the efficacy of platelet
      rich plasma (PRP) in treating knee osteoarthritis (OA) have been recently
      published. The purpose of the present study was (1) to perform an overview of
      overlapping systematic reviews investigating PRP for knee OA via evaluating
      methodological quality and risk of bias of systematic reviews and (2) to provide
      recommendations through the best evidence. METHODS: A systematic search of
      systematic reviews published through Feb 2017 was conducted using the MEDLINE,
      EMBASE and Cochrane Library. The methodological quality and risk of bias of
      included systematic reviews were assessed by AMSTAR instrument and ROBIS tool
      respectively. Best evidence choice procedure was conducted according to the Jadad
      decision algorithm. The systematic reviews with high quality of methodology and
      low risk of bias were selected ultimately. RESULTS: Ten systematic reviews were
      eligible for inclusion. The Jadad decision making tool suggested that the reviews
      with highest AMSTAR score should be selected. According to the ROBIS tool, there
      were 4 systematic reviews with low risk of bias and 6 with high risk of bias. As
      a result, two systematic reviews conducted by Dai et al and Meheux et al with
      highest AMSTAR score and low risk of bias were selected as the best evidence.
      CONCLUSIONS: The present overview demonstrates that PRP is an effective
      intervention in treating knee OA without increased risk of adverse events.
      Therefore, the present conclusions may help decision makers interpret and choose
      PRP with more confidence.

PMID- 29210207
TI  - Prevalence of knee osteoarthritis in a suburban, Srilankan, adult female
      population: a population-based study.
AB  - INTRODUCTION: Prevalence of knee osteoarthritis (KOA) has not been assessed in
      Sri Lanka, since 2006. This study aimed to determine the prevalence of clinical
      KOA and radiographic KOA and to assess the severity of it, among adult females of
      a suburban setting in Sri Lanka. METHODS: A cross-sectional survey was conducted
      among a representative sample of 666 females aged 50 years or more resident in
      Pita Kotte Medical Officer of Health area. Four physiotherapy graduates applied
      American College of Rheumatology (ACR) criteria by performing the clinical
      assessment in the households. Participants with clinical knee osteoarthritis were
      referred for radiography to identify radiographic osteoarthritis and to assess
      severity. Age standardized prevalence of clinical KOA for Sri Lanka was estimated
      based on population statistics of 2001 Census. RESULTS: Study included 666 adult
      females with a response rate of 99.4%. The mean age was 63.3 years (+/-9.29
      years). A total of 134 were found to satisfy ACR criteria resulting in a crude
      prevalence of clinical KOA of 20.1% (95% CI 17.0%-23.2%). Estimated age
      standardized prevalence of clinical KOA for Sri Lanka was 21.8% (95% CI 21.7
      21.9). Among those with clinical KOA 58.9% showed radiographic KOA and the
      prevalence of moderate/severe KOA among those with clinical KOA was 29.9%.
      CONCLUSION AND RECOMMENDATIONS: Prevalence of clinical KOA among the adult
      females over 50 years was high with considerable proportion of them being
      moderate /severe KOA. These findings should be used to advice the health
      authorities regarding improving preventive and curative services for KOA.

PMID- 29210209
TI  - Ranciere's writings applied to nursing: A radical and emancipatory political
      theory.

PMID- 29210208
TI  - Potential Effect Modifiers of the Association Between Physical Activity Patterns
      and Joint Symptoms in Middle-Aged Women.
AB  - OBJECTIVE: To examine whether body mass index (BMI), menopausal status, and
      hormone therapy (HT) use modify the association between physical activity (PA)
      patterns throughout middle age and the incidence and prevalence of joint symptoms
      in women in later middle age. METHODS: Data were from 6,661 participants (born
      1946-1951) in the Australian Longitudinal Study on Women's Health. Surveys, with
      questions on joint pain and stiffness, PA, height and weight, menopausal
      symptoms, and HT use, were completed every 3 years from 1998 to 2010. PA patterns
      were defined as none or low, low or meeting guidelines, fluctuating, or meeting
      guidelines at all times (reference pattern). Logistic regression was used to
      examine the association between PA patterns and prevalent (in 2010) and
      cumulative incident (1998-2010) joint symptoms and effect modification by
      patterns in BMI, menopausal status, and HT. RESULTS: The groups representing
      fluctuating PA (odds ratio [OR] 1.34 [99% confidence interval (99% CI) 1.04
      1.72]) and no or low PA (OR 1.60 [99% CI 1.08-2.35]) had higher odds of incident
      joint symptoms than those described as meeting guidelines at all times.
      Stratification by BMI showed that this association was statistically significant
      in the obese group only. No evidence for effect modification by menopausal status
      or HT use was found. The findings were similar for prevalent joint symptoms.
      CONCLUSION: Maintaining at least low levels of PA throughout middle age was
      associated with a lower prevalence and incidence of joint symptoms later in life.
      This apparent protective effect of PA on joint symptoms was stronger in obese
      women than in under- or normal-weight women, and not related to menopause or HT
      status.

PMID- 29210210
TI  - Value of double mucoperiosteal flaps to prevent restenosis in Draf IIb/III: First
      clinical report.

PMID- 29210211
TI  - Continuing Professional Development.

PMID- 29210213
TI  - Digest: The effect of the pollinator composition and abundance on pollen-related
      floral traits.

PMID- 29210214
TI  - ATP is a driving force in the repair of photosystem II during photoinhibition.
AB  - Repair of photosystem II (PSII) during photoinhibition involves replacement of
      photodamaged D1 protein by newly synthesized D1 protein. In this review, we
      summarize evidence for the indispensability of ATP in the degradation and
      synthesis of D1 during the repair of PSII. Synthesis of one molecule of the D1
      protein consumes more than 1,300 molecules of ATP equivalents. The degradation of
      photodamaged D1 by FtsH protease also consumes approximately 240 molecules of
      ATP. In addition, ATP is required for several other aspects of the repair of
      PSII, such as transcription of psbA genes. These requirements for ATP during the
      repair of PSII have been demonstrated by experiments showing that the synthesis
      of D1 and the repair of PSII are interrupted by inhibitors of ATP synthase and
      uncouplers of ATP synthesis, as well as by mutation of components of ATP
      synthase. We discuss the contribution of cyclic electron transport around
      photosystem I to the repair of PSII. Furthermore, we introduce new terms relevant
      to the regulation of the PSII repair, namely, "ATP-dependent regulation" and
      "redox-dependent regulation," and we discuss the possible contribution of the ATP
      dependent regulation of PSII repair under environmental stress.

PMID- 29210215
TI  - Longitudinal Relationships Between Positive Affect, Loneliness, and Suicide
      Ideation: Age-Specific Factors in a General Population.
AB  - The aims of this study were to analyze whether positive and negative affect,
      social support, and loneliness are factors longitudinally related to suicide
      ideation in the general population in different age groups. A total of 2,392
      individuals from a nationally representative sample of the Spanish general
      population were evaluated in 2011-2012 and in 2014-2015. After including relevant
      control variables in the analyses, lower positive affect was prospectively
      related to ideation in 18- to 59-year-old individuals, whereas feelings of
      loneliness were related to ideation in 60-year-and-older individuals. Social
      support was not associated with suicide ideation in any age group. These results
      are in line with the need for age-tailored suicide prevention programs. The
      present findings might also suggest that health care professionals should
      consider feelings of loneliness rather than social support to assess the presence
      of suicide ideation in older people.

PMID- 29210216
TI  - Improved Efficiency and Stability of Perovskite Solar Cells Induced by C?O
      Functionalized Hydrophobic Ammonium-Based Additives.
AB  - Because of the rapid rise of the efficiency, perovskite solar cells are currently
      considered as the most promising next-generation photovoltaic technology. Much
      effort has been made to improve the efficiency and stability of perovskite solar
      cells. Here, it is demonstrated that the addition of a novel organic cation of 2
      (6-bromo-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethan-1-ammonium iodide (2
      NAM), which has strong Lewis acid and base interaction (between C?O and Pb) with
      perovskite, can effectively increase crystalline grain size and reduce charge
      carrier recombination of the double cation FA0.83 MA0.17 PbI2.51 Br0.49
      perovskite film, thus boosting the efficiency from 17.1 +/- 0.8% to 18.6 +/- 0.9%
      for the 0.1 cm2 cell and from 15.5 +/- 0.5% to 16.5 +/- 0.6% for the 1.0 cm2
      cell. The champion cell shows efficiencies of 20.0% and 17.6% with active areas
      of 0.1 and 1.0 cm2 , respectively. Moreover, the hysteresis behavior is
      suppressed and the stability is improved. The result provides a promising route
      to further elevate efficiency and stability of perovskite solar cells by the fine
      tuning of triple organic cations.

PMID- 29210217
TI  - I131 reinforces antitumor activity of metuximab by reversing epithelial
      mesenchymal transition via VEGFR-2 signaling in hepatocellular carcinoma.
AB  - CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with
      the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab),
      a newly developed agent that targets CD147, as a radio-immunotherapy for local
      HCC, has been validated in clinical practice. However, the synergistic anticancer
      activity and molecular mechanism of different conjugated components within I131 
      mab remain unclear. In this study, the cytological experiments proved that I131 
      mab inhibited the proliferation and invasion of HCC cells. Mechanically, this
      inhibition effect was mainly mediated by the antibody component part of I131 
      mab, which could reverse the epithelial-mesenchymal transition of HCC cells
      partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of
      I131 on HCC cell proliferation and invasion is limited, whereas, when combined
      with metuximab, I131 significantly enhanced the sensitivity of HCC cells to CD147
      mab and consequently reinforced the anticancer effects of CD147-mab, suggesting
      that the two components of I131 -mab exerted synergistic anti-HCC capability.
      Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude
      mice showed that I131 -mab and CD147-mab significantly inhibited the growth of
      xenograft tumors and that I131 -mab was more effective than CD147-mab. In
      conclusion, our results elucidated the mechanism underlying the anti-HCC effects
      of I131 -mab and provided a theoretical foundation for the clinical application
      of I131 -mab.

PMID- 29210218
TI  - Testing an app for reporting health concerns-Experiences from older people and
      home care nurses.
AB  - AIMS AND OBJECTIVES: To explore the experiences of using an app among older
      people with home-based health care and their nurses. BACKGROUND: Few information
      and communication technology innovations have been developed and tested for older
      people with chronic conditions living at home with home-based health care
      support. Innovative ways to support older people's health and self-care are
      needed. DESIGN: Explorative qualitative design. METHODS: For 3 months to report
      health concerns, older people receiving home-based health care used an
      interactive app, which included direct access to self-care advice, graphs and a
      risk assessment model that sends alerts to nurses for rapid management.
      Interviews with older people (n = 17) and focus group discussions with home care
      nurses (n = 12) were conducted and analysed using thematic analysis. RESULTS: The
      findings reveal that a process occurs. Using the app, the older people
      participated in their care, and the app enabled learning and a new way of
      communication. The interaction gave a sense of security and increased self
      confidence among older people. The home care nurses viewed the alerts as
      appropriate for the management of health concerns. However, all participants
      experienced challenges in using new technology and had suggestions for
      improvement. CONCLUSIONS: The use of an app appears to increase the older
      people's participation in their health care and offers them an opportunity to be
      an active partner in their care. The app as a new way to interact with home care
      nurses increased the feeling of security. The older people were motivated to
      learn to use the app and described potential use for it in the future.
      IMPLICATIONS FOR PRACTICE: The use of an app should be considered as a useful
      information and communication technology innovation that can improve
      communication and accessibility for older people with home-based health care.

PMID- 29210219
TI  - Simple multimodal optical technique for evaluation of free/bound water and
      dispersion of human liver tissue.
AB  - The optical dispersion and water content of human liver were experimentally
      studied to estimate the optical dispersions of tissue scatterers and dry matter.
      Using temporal measurements of collimated transmittance [Tc(t)] of liver samples
      under treatment at different glycerol concentrations, free water and diffusion
      coefficient (Dgl) of glycerol in liver were found as 60.0% and 8.2*10-7  cm2/s,
      respectively. Bound water was calculated as the difference between the reported
      total water of 74.5% and found free water. The optical dispersion of liver was
      calculated from the measurements of refractive index (RI) of tissue samples made
      for different wavelengths between 400 and 1000 nm. Using liver and water optical
      dispersions at 20 degrees C and the free and total water, the dispersions for
      liver scatterers and dry matter were calculated. The estimated dispersions
      present a decreasing behavior with wavelength. The dry matter dispersion shows
      higher RI values than liver scatterers, as expected. Considering 600 nm, dry
      matter has an RI of 1.508, whereas scatterers have an RI of 1.444. These
      dispersions are useful to characterize the RI matching mechanism in optical
      clearing treatments, provided that [Tc(t)] and thickness measurements are
      performed during treatment. The knowledge of Dgl is also important for living
      tissue cryoprotection applications.

PMID- 29210220
TI  - Optical coherence tomography in gynecology: a narrative review.
AB  - Modern gynecologic practice requires noninvasive diagnostics techniques capable
      of detecting morphological and functional alterations in tissues of female
      reproductive organs. Optical coherence tomography (OCT) is a promising tool for
      providing imaging of biotissues with high resolution at depths up to 2 mm. Design
      of the customized probes provides wide opportunities for OCT use in gynecology.
      This paper contains a retrospective insight into the history of OCT employment in
      gynecology, an overview of the existing gynecologic OCT probes, including those
      for combination with other diagnostic modalities, and state-of-the-art
      application of OCT for diagnostics of tumor and nontumor pathologies of female
      genitalia. Perspectives of OCT both in diagnostics and treatment planning and
      monitoring in gynecology are overviewed.

PMID- 29210221
TI  - Heart-rate sensitive optical coherence angiography for measuring vascular changes
      due to posttraumatic brain injury in mice.
AB  - Traumatic brain injury (TBI) results in direct vascular disruption, triggering
      edema, and reduction in cerebral blood flow. Therefore, understanding the
      pathophysiology of brain microcirculation following TBI is important for the
      development of effective therapies. Optical coherence angiography (OCA) is a
      promising tool for evaluating TBI in rodent models. We develop an approach to OCA
      that uses the heart-rate frequency to discriminate between static tissue and
      vasculature. This method operates on intensity data and is therefore not phase
      sensitive. Furthermore, it does not require spatial overlap of voxels and thus
      can be applied to pre-existing datasets for which oversampling may not have been
      explicitly considered. Heart-rate sensitive OCA was developed for dynamic
      assessment of mouse microvasculature post-TBI. Results show changes occurring at
      5-min intervals within the first 50 min of injury.

PMID- 29210222
TI  - LED lighting increases the ecological impact of light pollution irrespective of
      color temperature.
AB  - Recognition of the extent and magnitude of night-time light pollution impacts on
      natural ecosystems is increasing, with pervasive effects observed in both
      nocturnal and diurnal species. Municipal and industrial lighting is on the cusp
      of a step change where energy-efficient lighting technology is driving a shift
      from "yellow" high-pressure sodium vapor lamps (HPS) to new "white" light
      emitting diodes (LEDs). We hypothesized that white LEDs would be more attractive
      and thus have greater ecological impacts than HPS due to the peak UV-green-blue
      visual sensitivity of nocturnal invertebrates. Our results support this
      hypothesis; on average LED light traps captured 48% more insects than were
      captured with light traps fitted with HPS lamps, and this effect was dependent on
      air temperature (significant light * air temperature interaction). We found no
      evidence that manipulating the color temperature of white LEDs would minimize the
      ecological impacts of the adoption of white LED lights. As such, large-scale
      adoption of energy-efficient white LED lighting for municipal and industrial use
      may exacerbate ecological impacts and potentially amplify phytosanitary pest
      infestations. Our findings highlight the urgent need for collaborative research
      between ecologists and electrical engineers to ensure that future developments in
      LED technology minimize their potential ecological effects.

PMID- 29210223
TI  - The role of reserves and anthropogenic habitats for functional connectivity and
      resilience of ephemeral wetlands.
AB  - Ecological reserves provide important wildlife habitat in many landscapes, and
      the functional connectivity of reserves and other suitable habitat patches is
      crucial for the persistence and resilience of spatially structured populations.
      To maintain or increase connectivity at spatial scales larger than individual
      patches, conservation actions may focus on creating and maintaining reserves
      and/or influencing management on non-reserves. Using a graph-theoretic approach,
      we assessed the functional connectivity and spatial distribution of wetlands in
      the Rainwater Basin of Nebraska, USA, an intensively cultivated agricultural
      matrix, at four assumed, but ecologically realistic, anuran dispersal distances.
      We compared connectivity in the current landscape to the historical landscape and
      putative future landscapes, and evaluated the importance of individual and
      aggregated reserve and non-reserve wetlands for maintaining connectivity.
      Connectivity was greatest in the historical landscape, where wetlands were also
      the most densely distributed. The construction of irrigation reuse pits for water
      storage has maintained connectivity in the current landscape by replacing
      destroyed wetlands, but these pits likely provide suboptimal habitat. Also,
      because there are fewer total wetlands (i.e., wetlands and irrigation reuse pits)
      in the current landscape than the historical landscape, and because the
      distribution of current wetlands is less clustered than that of historical
      wetlands, larger and longer dispersing, sometimes nonnative species may be
      favored over smaller, shorter dispersing species of conservation concern. Because
      of their relatively low number, wetland reserves do not affect connectivity as
      greatly as non-reserve wetlands or irrigation reuse pits; however, they likely
      provide the highest quality anuran habitat. To improve future levels of
      resilience in this wetland habitat network, management could focus on continuing
      to improve the conservation status of non-reserve wetlands, restoring wetlands at
      spatial scales that promote movements of shorter dispersing species, and further
      scrutinizing irrigation reuse pit removal by considering effects on functional
      connectivity for anurans, an emblematic and threatened group of organisms.
      However, broader conservation plans will need to give consideration to other
      wetland-dependent species, incorporate invasive species management, and address
      additional challenges arising from global change in social-ecological systems
      like the Rainwater Basin.

PMID- 29210224
TI  - Assessing habitat connectivity for ground-dwelling animals in an urban
      environment.
AB  - To ensure viable species populations in fragmented landscapes, individuals must
      be able to move between suitable habitat patches. Despite the increased interest
      in biodiversity assessment in urban environments, the ecological relevance of
      habitat connectivity in highly fragmented landscapes remains largely unknown. The
      first step to understanding the role of habitat connectivity in urban ecology is
      the challenging task of assessing connectivity in the complex patchwork of
      contrasting habitats that is found in cities.We developed a data-based framework,
      minimizing the use of subjective assumptions, to assess habitat connectivity that
      consists of the following sequential steps: (1) identification of habitat
      preference based on empirical habitat-use data; (2) derivation of habitat
      resistance surfaces evaluating various transformation functions; (3) modeling of
      different connectivity maps with electrical circuit theory (Circuitscape), a
      method considering all possible pathways across the landscape simultaneously; and
      (4) identification of the best connectivity map with information-theoretic model
      selection. We applied this analytical framework to assess habitat connectivity
      for the European hedgehog Erinaceus europaeus, a model species for ground
      dwelling animals, in the city of Zurich, Switzerland, using GPS track points from
      40 individuals.The best model revealed spatially explicit connectivity "pinch
      points," as well as multiple habitat connections. Cross-validation indicated the
      general validity of the selected connectivity model. The results show that both
      habitat connectivity and habitat quality affect the movement of urban hedgehogs
      (relative importance of the two variables was 19.2% and 80.8%, respectively), and
      are thus both relevant for predicting urban animal movements.Our study
      demonstrates that even in the complex habitat patchwork of cities, habitat
      connectivity plays a major role for ground-dwelling animal movement. Data-based
      habitat connectivity maps can thus serve as an important tool for city planners
      to identify habitat corridors and plan appropriate management and conservation
      measures for urban animals. The analytical framework we describe to model such
      connectivity maps is generally applicable to different types of habitat-use data
      and can be adapted to the movement scale of the focal species. It also allows
      evaluation of the impact of future landscape changes or management scenarios on
      habitat connectivity in urban landscapes.

PMID- 29210225
TI  - Urban warming trumps natural enemy regulation of herbivorous pests.
AB  - Trees provide ecosystem services that counter negative effects of urban habitats
      on human and environmental health. Unfortunately, herbivorous arthropod pests are
      often more abundant on urban than rural trees, reducing tree growth, survival,
      and ecosystem services. Previous research where vegetation complexity was reduced
      has attributed elevated urban pest abundance to decreased regulation by natural
      enemies. However, reducing vegetation complexity, particularly the density of
      overstory trees, also makes cities hotter than natural habitats. We ask how urban
      habitat characteristics influence an abiotic factor, temperature, and a biotic
      factor, natural enemy abundance, in regulating the abundance of an urban forest
      pest, the gloomy scale, (Melanaspis tenebricosa). We used a map of surface
      temperature to select red maple trees (Acer rubrum) at warmer and cooler sites in
      Raleigh, North Carolina, USA. We quantified habitat complexity by measuring
      impervious surface cover, local vegetation structural complexity, and landscape
      scale vegetation cover around each tree. Using path analysis, we determined that
      impervious surface (the most important habitat variable) increased scale insect
      abundance by increasing tree canopy temperature, rather than by reducing natural
      enemy abundance or percent parasitism. As a mechanism for this response, we found
      that increasing temperature significantly increases scale insect fecundity and
      contributes to greater population increase. Specifically, adult female M.
      tenebricosa egg sets increased by approximately 14 eggs for every 1 degrees C
      increase in temperature. Climate change models predict that the global climate
      will increase by 2-3 degrees C in the next 50-100 years, which we found would
      increase scale insect abundance by three orders of magnitude. This result
      supports predictions that urban and natural forests will face greater herbivory
      in the future, and suggests that a primary cause could be direct, positive
      effects of warming on herbivore fitness rather than altered trophic interactions.

PMID- 29210226
TI  - Fire severity and tree regeneration following bark beetle outbreaks: the role of
      outbreak stage and burning conditions.
AB  - The degree to which recent bark beetle (Dendroctonus ponderosae) outbreaks may
      influence fire severity and postfire tree regeneration is of heightened interest
      to resource managers throughout western North America, but empirical data on
      actual fire effects are lacking. Outcomes may depend on burning conditions (i.e.,
      weather during fire), outbreak severity, or intervals between outbreaks and
      subsequent fire. We studied recent fires that burned through green-attack/red
      stage (outbreaks <3 years before fire) and gray-stage (outbreaks 3-15 years
      before fire) subalpine forests dominated by lodgepole pine (Pinus contorta var.
      latifolia) in Greater Yellowstone, Wyoming, USA, to determine if fire severity
      was linked to prefire beetle outbreak severity and whether these two disturbances
      produced compound ecological effects on postfire tree regeneration. With field
      data from 143 postfire plots that burned under different conditions, we assessed
      canopy and surface fire severity, and postfire tree seedling density against
      prefire outbreak severity.In the green-attack/red stage, several canopy fire
      severity measures increased with prefire outbreak severity under moderate burning
      conditions. Under extreme conditions, few fire-severity measures were related to
      prefire outbreak severity, and effect sizes were of marginal biological
      significance. The percentage of tree stems and basal area killed by fire
      increased with more green-attack vs. red-stage trees (i.e., the earliest stages
      of outbreak). In the gray stage, by contrast, most fire-severity measures
      declined with increasing outbreak severity under moderate conditions, and fire
      severity was unrelated to outbreak severity under extreme burning conditions.
      Postfire lodgepole pine seedling regeneration was unrelated to prefire outbreak
      severity in either post-outbreak stage, but increased with prefire serotiny.
      Results suggest bark beetle outbreaks can affect fire severity in subalpine
      forests under moderate burning conditions, but have little effect on fire
      severity under extreme burning conditions when most large wildfires occur in this
      system. Thus, beetle outbreak severity was moderately linked to fire severity,
      but the strength and direction of the linkage depended on both endogenous
      (outbreak stage) and exogenous (fire weather) factors. Closely timed beetle
      outbreak and fire did not impart compound effects on tree regeneration,
      suggesting the presence of a canopy seedbank may enhance resilience to their
      combined effects.

PMID- 29210227
TI  - Simulating post-wildfire forest trajectories under alternative climate and
      management scenarios.
AB  - Post-fire predictions of forest recovery under future climate change and
      management actions are necessary for forest managers to make decisions about
      treatments. We applied the Climate-Forest Vegetation Simulator (Climate-FVS), a
      new version of a widely used forest management model, to compare alternative
      climate and management scenarios in a severely burned multispecies forest of
      Arizona, USA. The incorporation of seven combinations of General Circulation
      Models (GCM) and emissions scenarios altered long-term (100 years) predictions of
      future forest condition compared to a No Climate Change (NCC) scenario, which
      forecast a gradual increase to high levels of forest density and carbon stock. In
      contrast, emissions scenarios that included continued high greenhouse gas
      releases led to near-complete deforestation by 2111. GCM-emissions scenario
      combinations that were less severe reduced forest structure and carbon stock
      relative to NCC. Fuel reduction treatments that had been applied prior to the
      severe wildfire did have persistent effects, especially under NCC, but were
      overwhelmed by increasingly severe climate change. We tested six management
      strategies aimed at sustaining future forests: prescribed burning at 5, 10, or 20
      year intervals, thinning 40% or 60% of stand basal area, and no treatment. Severe
      climate change led to deforestation under all management regimes, but important
      differences emerged under the moderate scenarios: treatments that included
      regular prescribed burning fostered low density, wildfire-resistant forests
      composed of the naturally dominant species, ponderosa pine. Non-fire treatments
      under moderate climate change were forecast to become dense and susceptible to
      severe wildfire, with a shift to dominance by sprouting species. Current U.S.
      forest management requires modeling of future scenarios but does not mandate
      consideration of climate change effects. However, this study showed substantial
      differences in model outputs depending on climate and management actions.
      Managers should incorporate climate change into the process of analyzing the
      environmental effects of alternative actions.

PMID- 29210228
TI  - Centennial impacts of fragmentation on the canopy structure of tropical montane
      forest.
AB  - Fragmentation poses one of the greatest threats to tropical forests with short
      term changes to the structure of forest canopies affecting microclimate, tree
      mortality, and growth. Yet the long-term effects of fragmentation are poorly
      understood because (1) most effects require many decades to materialize, but long
      term studies are very rare, (2) the effects of edges on forest canopy structure
      as a function of fragment size are unknown, and (3) edge effects are often
      confounded by fragment shape. We quantified the long-term (centennial) effects of
      fragmentation on forest canopy structure using airborne light detection and
      ranging (LiDAR) of 1060 Hawaiian rain forest fragments ranging in size from 0.02
      to 1000 ha, created more than 130 years ago by flowing lava. Along with distance
      from edge, we developed a metric, minimum span, to gain additional insight into
      edge effects on three measures of canopy structure: canopy height, height
      variation, and gap fraction.Fragment size was a strong determinant of the three
      structural variables. Larger fragments had greater average height, larger
      variation in height, and smaller gap fraction. Minimum span had a large effect on
      the depth and magnitude of edge effects for the three structural variables.
      Locations associated with high span values (those surrounded by more forest
      habitat) showed little effect of distance to fragment edge. In contrast,
      locations with low span values (those more exposed to edges) were severely
      limited in canopy height, showed lower height variation, and were associated with
      greater gap fraction values. The minimum span attribute allows for a more
      accurate characterization of edge as well as fragment-level effects, and when
      combined with high resolution imagery, can improve planning of protected areas
      for long-term ecological sustainability and biodiversity protection.

PMID- 29210229
TI  - Spectroscopic determination of leaf morphological and biochemical traits for
      northern temperate and boreal tree species.
AB  - The morphological and biochemical properties of plant canopies are strong
      predictors of photosynthetic capacity and nutrient cycling. Remote sensing
      research at the leaf and canopy scales has demonstrated the ability to
      characterize the biochemical status of vegetation canopies using reflectance
      spectroscopy, including at the leaf level and canopy level from air- and
      spaceborne imaging spectrometers. We developed a set of accurate and precise
      spectroscopic calibrations for the determination of leaf chemistry (contents of
      nitrogen, carbon, and fiber constituents), morphology (leaf mass per area,
      Marea), and isotopic composition (delta15N) of temperate and boreal tree species
      using spectra of dried and ground leaf material. The data set consisted of leaves
      from both broadleaf and needle-leaf conifer species and displayed a wide range in
      values, determined with standard analytical approaches: 0.7-4.4% for nitrogen
      (Nmass), 42-54% for carbon (Cmass), 17-58% for fiber (acid-digestible fiber,
      ADF), 7-44% for lignin (acid-digestible lignin, ADL), 3-31% for cellulose, 17-265
      g/m2 for Marea, and -9.40/00 to 0.80/00 for delta15N. The calibrations were
      developed using a partial least-squares regression (PLSR) modeling approach
      combined with a novel uncertainty analysis. Our PLSR models yielded model
      calibration (independent validation shown in parentheses) R2 and the root mean
      square error (RMSE) values, respectively, of 0.98 (0.97) and 0.10% (0.13%) for
      Nmass, R2 = 0.77 (0.73) and RMSE = 0.88% (0.95%) for Cmass, R2 = 0.89 (0.84) and
      RMSE = 2.8% (3.4%) for ADF, R2 = 0.77 (0.69) and RMSE = 2.4% (3.9%) for ADL, R2 =
      0.77 (0.72) and RMSE = 1.4% (1.9%) for leaf cellulose, R2 = 0.62 (0.60) and RMSE
      = 0.910/00 (1.50/00) for delta15N, and R2 = 0.88 (0.87) with RMSE = 17.2 g/m2
      (22.8 g/m2) for Marea. This study demonstrates the potential for rapid and
      accurate estimation of key foliar traits of forest canopies that are important
      for ecological research and modeling activities, with a single calibration
      equation valid over a wide range of northern temperate and boreal species and
      leaf physiognomies. The results provide the basis to characterize important
      variability between and within species, and across ecological gradients using a
      rapid, cost-effective, easily replicated method.

PMID- 29210230
TI  - Mixed-conifer forests of central Oregon: effects of logging and fire exclusion
      vary with environment.
AB  - Twentieth-century land management has altered the structure and composition of
      mixed-conifer forests and decreased their resilience to fire, drought, and
      insects in many parts of the Interior West. These forests occur across a wide
      range of environmental settings and historical disturbance regimes, so their
      response to land management is likely to vary across landscapes and among
      ecoregions. However, this variation has not been well characterized and hampers
      the development of appropriate management and restoration plans. We identified
      mixed-conifer types in central Oregon based on historical structure and
      composition, and successional trajectories following recent changes in land use,
      and evaluated how these types were distributed across environmental gradients. We
      used field data from 171 sites sampled across a range of environmental settings
      in two subregions: the eastern Cascades and the Ochoco Mountains.We identified
      four forest types in the eastern Cascades and four analogous types with lower
      densities in the Ochoco Mountains. All types historically contained ponderosa
      pine, but differed in the historical and modern proportions of shade-tolerant vs.
      shade-intolerant tree species. The Persistent Ponderosa Pine and Recent Douglas
      fir types occupied relatively hot-dry environments compared to Recent Grand Fir
      and Persistent Shade Tolerant sites, which occupied warm-moist and cold-wet
      environments, respectively. Twentieth-century selective harvesting halved the
      density of large trees, with some variation among forest types. In contrast, the
      density of small trees doubled or tripled early in the 20th century, probably due
      to land-use change and a relatively cool, wet climate. Contrary to the common
      perception that dry ponderosa pine forests are the most highly departed from
      historical conditions, we found a greater departure in the modern composition of
      small trees in warm-moist environments than in either hot-dry or cold-wet
      environments. Furthermore, shade-tolerant trees began infilling earlier in cold
      wet than in hot-dry environments and also in topographically shaded sites in the
      Ochoco Mountains. Our new classification could be used to prioritize management
      that seeks to restore structure and composition or create resilience in mixed
      conifer forests of the region.

PMID- 29210231
TI  - A framework to optimize the restoration and retention of large mature forest
      tracts in managed boreal landscapes.
AB  - The decreasing abundance of mature forests and their fragmentation have been
      identified as major threats for the preservation of biodiversity in managed
      landscapes. In this study, we developed a multi-level framework to coordinate
      forest harvestings so as to optimize the retention or restoration of large mature
      forest tracts in managed forests. We used mixed-integer programming for this
      optimization, and integrated realistic management assumptions regarding stand
      yield and operational harvest constraints. The model was parameterized for
      eastern Canadian boreal forests, where clear-cutting is the main silvicultural
      system, and is used to examine two hypotheses. First, we tested if mature forest
      tract targets had more negative impacts on wood supplies when implemented in
      landscapes that are very different from targeted conditions. Second, we tested
      the hypothesis that using more partial cuts can be useful to attenuate the
      negative impacts of mature forest targets on wood supplies. The results indicate
      that without the integration of an explicit mature forest tract target, the
      optimization leads to relatively high fragmentation levels. Forcing the retention
      or restoration of large mature forest tracts on 40% of the landscapes had
      negative impacts on wood supplies in all types of landscapes, but these impacts
      were less important in landscapes that were initially fragmented. This counter
      intuitive result is explained by the presence in the models of an operational
      constraint that forbids diffuse patterns of harvestings, which are more costly.
      Once this constraint is applied, the residual impact of the mature forest tract
      target is low. The results also indicate that partial cuts are of very limited
      use to attenuate the impacts of mature forest tract targets on wood supplies in
      highly fragmented landscapes. Partial cuts are somewhat more useful in landscapes
      that are less fragmented, but they have to be well coordinated with clearcut
      schedules in order to contribute efficiently to conservation objectives. This
      modeling framework could easily be adapted and parameterized to test hypotheses
      or to optimize restoration schedules in landscapes where issues such as forest
      fragmentation and the abundance of mature or old-growth forests are a concern.

PMID- 29210232
TI  - Bayesian networks for habitat suitability modeling: a potential tool for
      conservation planning with scarce resources.
AB  - Bayesian networks (BN) have been increasingly used for habitat suitability
      modeling of threatened species due to their potential to construct robust models
      with limited survey data. However, previous applications of this approach have
      only occurred in countries where human and budget resources are highly available,
      but the highest concentrations of threatened vertebrates globally are located in
      the tropics where resources are much more limited. We assessed the effectiveness
      of Bayesian networks in generating habitat suitability models in Thailand, a
      biodiversity-rich country where the knowledge base is typically sparse for a wide
      range of threatened species. The Bayesian network approach was used to generate
      habitat suitability maps for 52 threatened vertebrate species in Thailand, using
      a range of evidence types, from relatively well-documented species with good
      local knowledge to poorly documented species, with few local experts. Published
      information and expert knowledge were used to define habitat requirements. Focal
      species were categorized into 22 groups based on known habitat preferences, and
      then habitat suitability models were constructed with outcomes represented
      spatially. Models had a consistent structure with three major components:
      potential habitat, known range, and threat level. Model classification
      sensitivity was tested using presence-only field data for 21 species. Habitat
      models for 12 species were relatively sensitive (>70% congruency between observed
      and predicted locations), three were moderately congruent, and six were poor.
      Classification sensitivity tended to be high for bird models and moderate for
      mammals, whereas sensitivity for reptiles was low, presumably reflecting the
      relatively poor knowledge base for reptiles in the region. Bayesian network
      models show significant potential for biodiversity-rich regions with scarce
      resources, although they require further refinement and testing. It is possible
      that one detailed ecological study is sufficient to develop a model with
      reasonable sensitivity, but BN models for species groups with no quantitative
      data continue to be problematic.

PMID- 29210233
TI  - Effects of fine-scale forest habitat quality on movement and settling decisions
      in juvenile pond-breeding salamanders.
AB  - A better understanding of how individuals respond to variation in habitat quality
      while moving through heterogeneous habitats is needed to predict ecological
      phenomena at larger scales, such as local population and metapopulation dynamics.
      We sought to identify how fine-scale habitat quality affects the decisions of
      juvenile pond-breeding salamanders (Ambystoma maculatum and A. annulatum) to
      cease dispersive movements away from their natal pond, select a refuge, and
      settle. Because of the acute susceptibility of juvenile amphibians to evaporative
      water loss in terrestrial habitats, we predicted that they possess mechanisms for
      adjusting their behavior in response to variations in fine-scale habitat quality.
      We used experimental field enclosures to isolate the effects of habitat quality
      on settling behavior and employed generalized linear mixed models to examine how
      manipulations in canopy cover (closed or open) and microhabitat (control,
      compacted soils, high coarse woody debris, high burrow density), along with
      environmental variables (rainfall and air temperature), affect the individual's
      probability of settling. Our results indicated that A. maculatum and A. annulatum
      had a 10% and 30% decreased probability of settling in open-canopy clearcut
      habitat, respectively, compared to closed-canopy forest habitat. In addition, A.
      annulatum were 24% less likely to settle in compacted soil treatments. Although
      the settlement probability of A. annulatum did not depend on refuge availability,
      A. maculatum were 18% and 25% more likely to settle under conditions of high
      burrow density and high coarse woody debris, respectively. These findings make a
      unique contribution to our understanding of amphibian movement ecology by
      demonstrating how the interplay of external factors and individual behavior
      produce observed patterns of movement and habitat selection.

PMID- 29210234
TI  - Spatio-temporal dynamics of ocean conditions and forage taxa reveal regional
      structuring of seabird-prey relationships.
AB  - Studies of predator-prey demographic responses and the physical drivers of such
      relationships are rare, yet essential for predicting future changes in the
      structure and dynamics of marine ecosystems. Here, we hypothesize that predator
      prey relationships vary spatially in association with underlying physical ocean
      conditions, leading to observable changes in demographic rates, such as
      reproduction. To test this hypothesis, we quantified spatio-temporal variability
      in hydrographic conditions, krill, and forage fish to model predator (seabird)
      demographic responses over 18 years (1990-2007). We used principal component
      analysis and spatial correlation maps to assess coherence among ocean conditions,
      krill, and forage fish, and generalized additive models to quantify interannual
      variability in seabird breeding success relative to prey abundance. The first
      principal component of four hydrographic measurements yielded an index that
      partitioned "warm/weak upwelling" and "cool/strong upwelling" years. Partitioning
      of krill and forage fish time series among shelf and oceanic regions yielded
      spatially explicit indicators of prey availability. Krill abundance within the
      oceanic region was remarkably consistent between years, whereas krill over the
      shelf showed marked interannual fluctuations in relation to ocean conditions.
      Anchovy abundance varied on the shelf, and was greater in years of strong
      stratification, weak upwelling and warmer temperatures. Spatio-temporal
      variability of juvenile forage fish co-varied strongly with each other and with
      krill, but was weakly correlated with hydrographic conditions. Demographic
      responses between seabirds and prey availability revealed spatially variable
      associations indicative of the dynamic nature of "predator-habitat"
      relationships. Quantification of spatially explicit demographic responses, and
      their variability through time, demonstrate the possibility of delineating
      specific critical areas where the implementation of protective measures could
      maintain functions and productivity of central place foraging predators.

PMID- 29210235
TI  - Radiocarbon dating of American pika fecal pellets provides insights into
      population extirpations and climate refugia.
AB  - The American pika (Ochotona princeps) has become a species of concern for its
      sensitivity to warm temperatures and potential vulnerability to global warming.
      We explored the value of radiocarbon dating of fecal pellets to address questions
      of population persistence and timing of site extirpation. Carbon was extracted
      from pellets collected at 43 locations in the western Great Basin, USA, including
      three known occupied sites and 40 sites of uncertain status at range margins or
      where previous studies indicated the species is vulnerable. We resolved
      calibrated dates with high precision (within several years), most of which fell
      in the period of the mid-late 20th century bomb curve. The two-sided nature of
      the bomb curve renders far- and near-side dates of equal probability, which are
      separated by one to four decades. We document methods for narrowing resolution to
      one age range, including stratigraphic analysis of vegetation collected from pika
      haypiles. No evidence was found for biases in atmospheric 14C levels due to
      fossil-derived or industrial CO2 contamination. Radiocarbon dating indicated that
      pellets can persist for >59 years; known occupied sites resolved contemporary
      dates. Using combined evidence from field observations and radiocarbon dating,
      and the Bodie Mountains as an example, we propose a historical biogeographic
      scenario for pikas in minor Great Basin mountain ranges adjacent to major
      cordillera, wherein historical climate variability led to cycles of extirpation
      and recolonization during alternating cool and warm centuries. Using this model
      to inform future dynamics for small ranges in biogeographic settings similar to
      the Bodie Mountains in California, extirpation of pikas appears highly likely
      under directional warming trends projected for the next century, even while
      populations in extensive cordillera (e.g., Sierra Nevada, Rocky Mountains,
      Cascade Range) are likely to remain viable due to extensive, diverse habitat and
      high connectivity.

PMID- 29210236
TI  - Supplemental feeding alters migration of a temperate ungulate.
AB  - Conservation of migration requires information on behavior and environmental
      determinants. The spatial distribution of forage resources, which migration
      exploits, often are altered and may have subtle, unintended consequences.
      Supplemental feeding is a common management practice, particularly for ungulates
      in North America and Europe, and carryover effects on behavior of this
      anthropogenic manipulation of forage are expected in theory, but have received
      limited empirical evaluation, particularly regarding effects on migration. We
      used global positioning system (GPS) data to evaluate the influence of winter
      feeding on migration behavior of 219 adult female elk (Cervus elaphus) from 18
      fed ranges and 4 unfed ranges in western Wyoming. Principal component analysis
      revealed that the migratory behavior of fed and unfed elk differed in distance
      migrated, and the timing of arrival to, duration on, and departure from summer
      range. Fed elk migrated 19.2 km less, spent 11 more days on stopover sites,
      arrived to summer range 5 days later, resided on summer range 26 fewer days, and
      departed in the autumn 10 days earlier than unfed elk. Time-to-event models
      indicated that differences in migratory behavior between fed and unfed elk were
      caused by altered sensitivity to the environmental drivers of migration. In
      spring, unfed elk migrated following plant green-up closely, whereas fed elk
      departed the feedground but lingered on transitional range, thereby delaying
      their arrival to summer range. In autumn, fed elk were more responsive to low
      temperatures and precipitation events, causing earlier departure from summer
      range than unfed elk. Overall, supplemental feeding disconnected migration by fed
      elk from spring green-up and decreased time spent on summer range, thereby
      reducing access to quality forage. Our findings suggest that ungulate migration
      can be substantially altered by changes to the spatial distribution of resources,
      including those of anthropogenic origin, and that management practices applied in
      one season may have unintended behavioral consequences in subsequent seasons.

PMID- 29210237
TI  - Cost-efficient fenced reserves for conservation: single large or two small?
AB  - Fences that exclude alien invasive species are used to reduce predation pressure
      on reintroduced threatened wildlife. Planning these continuously managed systems
      of reserves raises an important extension of the Single Large or Several Small
      (SLOSS) reserve planning framework: the added complexity of ongoing management.
      We investigate the long-term cost-efficiency of a single large or two small
      predator exclusion fences in the arid Australian context of reintroducing bilbies
      Macrotis lagotis, and we highlight the broader significance of our results with
      sensitivity analysis. A single fence more frequently results in a much larger net
      cost than two smaller fences. We find that the cost-efficiency of two fences is
      robust to strong demographic and environmental uncertainty, which can help
      managers to mitigate the risk of incurring high costs over the entire life of the
      project.

PMID- 29210238
TI  - Beyond seasonal climate: statistical estimation of phenological responses to
      weather.
AB  - Phenological events, such as the timing of flowering or insect emergence, are
      influenced by a complex combination of climatic and non-climatic factors.
      Although temperature is generally considered most important, other weather events
      such as frosts and precipitation events can also influence many species'
      phenology. Non-climatic variables such as photoperiod and site-specific habitat
      characteristics can also have important effects on phenology. Forecasting
      phenological shifts due to climate change requires understanding and quantifying
      how these multiple factors combine to affect phenology. However, current
      approaches to analyzing phenological data have a limited ability for quantifying
      multiple drivers simultaneously. Here, we use a novel statistical approach to
      estimate the combined effects of multiple variables, including local weather
      events, on the phenology of several taxa (a tree, an insect, and a fungus). We
      found that thermal forcing had a significant positive effect on each species,
      frost events delayed the phenology of the tree and butterfly, and precipitation
      had a positive effect on fungal fruiting. Using data from sites across
      latitudinal gradients, we found that these effects are remarkably consistent
      across sites once latitude and other site effects are accounted for. This
      consistency suggests an underlying biological response to these variables that is
      not commonly estimated using data from field observations. This approach's
      flexibility will be useful for forecasting ongoing phenological responses to
      changes in climate variability in addition to seasonal trends.

PMID- 29210239
TI  - Bycatch mortality of endangered coho salmon: impacts, solutions, and aboriginal
      perspectives.
AB  - We used biotelemetry and human dimensions surveys to explore potential solutions
      to migration mortality of an endangered population of coho salmon caught as
      bycatch in an aboriginal beach seine fishery. From 2009 to 2011, 182 wild coho
      salmon caught as bycatch in the lower Fraser River (Canada) were radio-tagged and
      tracked as they attempted to complete their migrations to natal spawning areas
      over 300 km upstream. Failure to survive to reach terminal radio receiving
      stations averaged 39% over three years. This mortality estimate is low compared
      to those obtained from telemetry studies on other salmon fisheries in the Fraser
      River. However, this value is markedly higher than the mortality estimate
      currently used to manage the fishery's impact. It is also in contrast to the
      perceptions of the majority of aboriginal fishers, who did not think survival of
      coho salmon is affected by capture and release from their fishery. Increased
      probability of survival was associated with lower reflex impairment, which is
      consistent with previous findings. Reflex impairment was positively correlated
      with entanglement time, suggesting that greater efforts by the fishers to release
      bycatch from their nets quickly would minimize post-release mortality. Survey
      responses by aboriginal fishers also suggested that they are receptive to
      employing new bycatch handling methods if they are shown to increase post-release
      survival. However, attempts to facilitate revival of a subset of captured fish
      using cylindrical in-river recovery bags did not improve migration success.
      Fisheries managers could use the new information from this study to better
      quantify impacts and evaluate different harvest options. Since aboriginal fishers
      were receptive to using alternate handling methods, efforts to improve knowledge
      on minimizing reflex impairment through reductions in handling time could help
      increase bycatch survival. Such a direct integration of social science and
      applied ecology is a novel approach to understanding conservation issues that can
      better inform meaningful actions to promote species recovery.

PMID- 29210241
TI  - Does landscape context mediate the nature of density dependence for a coral reef
      fish?
AB  - Over-harvest and landscape change are two of the greatest threats to marine
      ecosystems. Over-harvest may directly affect key population regulation mechanisms
      (e.g., density dependence), with the magnitude of the effects being further
      influenced by changes in landscape structure and associated resource
      availability. Because resource availability and conspecific density often co-vary
      within the natural landscape, manipulative experiments are needed to understand
      how changes in these two drivers may affect density dependence in wild
      populations. We used a common, shoaling, coral reef fish (white grunt, Haemulon
      plumierii) as our model species, and manipulated fish densities and landscape
      context of artificial reef habitats to assess the effects of each on fish
      condition. We found evidence of inverse density dependence, where individual
      condition was positively related to conspecific density; landscape context had
      little effect. Mean grunt condition on natural patch reefs was similar to that
      for our low grunt density treatment artificial reefs, possibly due to differences
      in fish densities or landscape context. These findings suggest that over-harvest
      may have detrimental effects on wild populations that extend beyond mere
      reductions in population size, especially for group-living species.

PMID- 29210240
TI  - A metacommunity perspective on source-sink dynamics and management: the Baltic
      Sea as a case study.
AB  - The degree to which metapopulation processes influence fish stock dynamics is a
      largely unresolved issue in marine science and management, especially for highly
      mobile species such as Atlantic cod (Gadus morhua) and herring (Clupea harengus).
      The Baltic Sea comprises a heterogeneous oceanographic environment that
      structures the spatial and temporal distribution of the dominant species cod,
      herring, and sprat (Sprattus sprattus). Despite local differences, the stocks are
      traditionally managed as homogeneous units. Here, we present a metacommunity
      perspective on source-sink dynamics of Baltic Sea fish stocks by using a
      spatially disaggregated statistical food web model. The model is fitted to area
      specific time series of multiple abiotic and biotic variables using state-space
      methods. Our analysis reveals pronounced net fluxes between areas, indicative of
      source-sink dynamics, as well as area-specific differences in species
      interactions (i.e., density dependence, competition, and predator-prey) and the
      degree of fishing and climate impact on survival and recruitment. Furthermore,
      model simulations show that decreasing exploitation pressure in the source area
      for cod (without reallocating fishing effort) produces an increase in neighboring
      sink habitats, but a decline of prey species in response to increased predation.
      Our approach provides valuable insight concerning metacommunity-structuring of
      marine fish and may serve as an important tool for implementing sustainable
      management strategies under the ecosystem approach to marine and fisheries
      management.

PMID- 29210242
TI  - Agricultural practices indirectly influence plant productivity and ecosystem
      services through effects on soil biota.
AB  - It is well established that agricultural practices alter the composition and
      diversity of soil microbial communities. However, the impact of changing soil
      microbial communities on the functioning of the agroecosystems is still poorly
      understood. Earlier work showed that soil tillage drastically altered microbial
      community composition. Here we tested, using an experimental grassland (Lolium,
      Trifolium, Plantago) as a model system, whether soil microbial communities from
      conventionally tilled (CT) and non-tilled (NT) soils have different influences on
      plant productivity and nutrient acquisition. We specifically focus on arbuscular
      mycorrhizal fungi (AMF), as they are a group of beneficial soil fungi that can
      promote plant productivity and ecosystem functioning and are also strongly
      affected by tillage management.Soil microbial communities from CT and NT soils
      varied greatly in their effects on the grassland communities. Communities from CT
      soil increased overall biomass production more than soil communities from NT
      soil. This effect was mainly due to a significant growth promotion of Trifolium
      by CT microorganisms. In contrast to CT soil inoculum, NT soil inoculum increased
      plant phosphorus concentration and total plant P content, demonstrating that the
      soil microbial communities from NT fields enhance P uptake. Differences in AM
      fungal community composition resulting, for instance, in twofold greater hyphal
      length in NT soil communities when compared to CT, are the most likely
      explanation for the different plant responses to CT and NT soil inocula.A range
      of field studies have shown that plant P uptake increases when farmers change to
      conservation tillage or direct seeding. Our results indicate that this enhanced P
      uptake results from enhanced hyphal length and an altered AM fungal community.
      Our results further demonstrate that agricultural management practices indirectly
      influence ecosystem services and plant community structure through effects on
      soil biota.

PMID- 29210243
TI  - Influential disease foci in epidemics and underlying mechanisms: a field
      experiment and simulations.
AB  - Pathogen invasions pose a growing threat to ecosystem stability and public
      health. Guidelines for the timing and spatial extent of control measures for
      pathogen invasions are currently limited, however. We conducted a field
      experiment using wheat (Triticum aestivum) stripe rust, caused by the wind
      dispersed fungus Puccinia striiformis, to study the extent to which host
      heterogeneity in an initial outbreak focus influences subsequent disease spread.
      We varied the frequency of susceptible host plants in an initial outbreak focus
      and in the non-focus of experimental plots, and observed the progress of
      epidemics produced by artificial inoculation. The frequency of susceptible hosts
      in the initial outbreak focus increased the spread of stripe rust in the
      experimental plots, while frequency of susceptible hosts outside the initial
      outbreak focus did not. This suggests that factors influencing pathogen
      reproduction in the initial outbreak focus are key to the control of epidemics of
      stripe rust. Two mechanisms may underlie the field results. The first is the
      continuing, direct infection of susceptible hosts in areas outside the initial
      outbreak focus by disease propagules arriving from the initial outbreak focus.
      The second is highly local proliferation of disease caused by direct descendants
      of colonizing individuals originating from the initial outbreak focus. We
      considered these two alternatives in simulations of a generalized pathogen
      exhibiting fat-tailed dispersal, similar to P. striiformis. Simulations showed a
      dominant effect of conditions in the initial outbreak focus, in agreement with
      the field experiment, but indicated that, over time, this dominance may erode.
      Analysis of the duration of focal dominance led to the conclusion that both
      mechanisms contribute to the phenomenon of focal dominance, and that the
      frequency of susceptible hosts in the initial outbreak focus had a stronger
      influence when the proportion of propagules that remained local during dispersal
      was higher. Overall, our results suggest that targeting pathogen reproduction in
      the initial outbreak focus will have a disproportionately large impact on
      subsequent epidemic spread.

PMID- 29210244
TI  - Biological soil crusts across disturbance-recovery scenarios: effect of grazing
      regime on community dynamics.
AB  - Grazing represents one of the most common disturbances in drylands worldwide,
      affecting both ecosystem structure and functioning. Despite the efforts to
      understand the nature and magnitude of grazing effects on ecosystem components
      and processes, contrasting results continue to arise. This is particularly
      remarkable for the biological soil crust (BSC) communities (i.e., cyanobacteria,
      lichens, and bryophytes), which play an important role in soil dynamics. Here we
      evaluated simultaneously the effect of grazing impact on BSC communities
      (resistance) and recovery after livestock exclusion (resilience) in a semiarid
      grassland of Central Mexico. In particular, we examined BSC species distribution,
      species richness, taxonomical group cover (i.e., cyanobacteria, lichen,
      bryophyte), and composition along a disturbance gradient with different grazing
      regimes (low, medium, high impact) and along a recovery gradient with differently
      aged livestock exclosures (short-, medium-, long-term exclusion). Differences in
      grazing impact and time of recovery from grazing both resulted in slight changes
      in species richness; however, there were pronounced shifts in species composition
      and group cover. We found we could distinguish four highly diverse and dynamic
      BSC species groups: (1) species with high resistance and resilience to grazing,
      (2) species with high resistance but low resilience, (3) species with low
      resistance but high resilience, and (4) species with low resistance and
      resilience. While disturbance resulted in a novel diversity configuration, which
      may profoundly affect ecosystem functioning, we observed that 10 years of
      disturbance removal did not lead to the ecosystem structure found after 27 years
      of recovery. These findings are an important contribution to our understanding of
      BCS dynamics from a species and community perspective placed in a land use change
      context.

PMID- 29210245
TI  - Health, Healthcare and Ageing Populations in Europe, a Human Rights Challenge for
      European Health Systems.
AB  - Demographic changes (ageing populations) are a challenge for European health
      systems. Innovative solutions must ensure elderly patients equitable access to
      good quality, affordable healthcare. De-centralisation and de
      institutionalisation in healthcare for the elderly have become policy priorities
      for European countries. Local governments must have sufficient experience for the
      necessary integration of health and social services. New ways of looking at
      health care systems are necessary for reasons of quality, accessibility, and
      costs-effectiveness. The implementation and co-ordinated monitoring of the health
      and care rights of the aged in Europe should be given full attention. There
      needs to be a handbook on elderly as well as an ombudsman. The exchange of
      experiences and best practices, oversight of the quality and effectiveness of the
      health- and care services and the system as such are indispensable.

PMID- 29210246
TI  - Quality Registries in Sweden, Healthcare Improvements and Elderly Persons with
      Cognitive Impairments.
AB  - Policy-makers, the medical industry and researchers are demonstrating a keen
      interest in the potential of large registries of patient data, both nationally
      and internationally. The registries offer promising ways to measure and develop
      operational quality within health and medical care services. As a result of
      certain favourable patient data regulations and government funding, the
      development of quality registries is advanced in Sweden. The combination of
      increasing demand for more cost-efficient healthcare that can accommodate the
      demographic development of a rapidly ageing population, and the emergence of
      eHealth with an increasing digitalisation of patient data, calls attention to
      quality registries as a possible way for healthcare improvements. However, even
      if the use of registries has many advantages, there are some drawbacks from a
      patient privacy point of view. This article aims to analyse this growing
      interdependence of quality registries for the healthcare sector. It discusses
      some lessons from the Swedish case, with particular focus on the collection of
      data from elderly persons with cognitive impairments.

PMID- 29210247
TI  - Access to Care in France for Elderly Immigrants from North Africa: Influence of
      Socio-cultural Factors (the MATC Survey).
AB  - France is faced with an ageing migrant population, and in the institutions for
      elderly, migrants represent only 4% and very few come from the Maghreb. Is it the
      result of a kind of discrimination or of other factors such as culture and
      traditions? In France migrants have access to aid and prevention of dependency
      plans. The reluctance to enter into institutions is maintained by the fear of
      cultural abuse and/or language barriers, and difficulties in financial and
      administrative matters. From the interviews of the MATC survey, we have pointed
      out the importance of culture and the tradition of filial piety. Nevertheless,
      solidarity in the family is decreasing but remains the basis of the care support
      to the elderly. The will to keep them in the family may limit both the diagnosis
      and the access to specific care. This attitude contributes to a kind of self
      discrimination.

PMID- 29210248
TI  - The View of the European Court of Human Rights on Competent Patients' Right of
      Informed Consent. Research in the Light of Articles 3 and 8 of the European
      Convention on Human Rights.
AB  - It is an internationally recognized principle that patients should give their
      informed consent to a treatment in order to avoid a violation of their right to
      personal autonomy. This article discusses this principle in the light of Articles
      3 and 8 of The European Convention on Human Rights and the view of the European
      Court of Human Rights on this matter. Indeed, nowadays more complaints related to
      (the lack of) informed consent not only concern a possible violation of Article 8
      of the Convention, but Article 3 has also gained importance, especially when a
      treatment is intrusive.

PMID- 29210249
TI  - Closing the Gap: A Human Rights Approach towards Social Determinants of Health.
AB  - Social determinants of health are major contributors to population health as well
      as health inequalities. The public perception that health inequalities that arise
      from these social determinants are unjust seems to be widespread across
      societies. Nevertheless, there is also scepticism about the progress in the
      implementation of actual policies to reduce health inequalities. Scholars,
      activists and policy makers from various disciplinary backgrounds increasingly
      stress the value of the human rights approach to support policies addressing
      health inequalities, and to hold actors in policies to address social
      determinants accountable for these inequalities. The 'right to health', in
      conjunction with the other health-related human rights, captures most elements of
      social determinants of health, and makes clear appeals to the governmental
      authorities at all levels to take action when social injustices occur. Existing
      judicial and non-judicial cases show us how human rights can be instrumental in
      addressing inequalities in health.

PMID- 29210250
TI  - European Court of Human Rights.

PMID- 29210251
TI  - Lightning or Lightning Bug: The Role of the Language Gap and the Access to Proper
      Information on Entitlements in Cross-border Patient Mobility.
AB  - The language barrier and the lack of reliable information were identified as
      major practical obstacles of European patient mobility. Patients are highly
      concerned about the ability to communicate with their doctors when obtaining
      healthcare in a country where they do not speak the local language, as well as
      they find it complicated to gather all the necessary information about an
      unfamiliar healthcare system or about their cross-border healthcare entitlements
      conferred on them by the Union legislation. In a multilingual and patient
      friendly European Union these issues must be tackled in order to ensure effective
      healthcare and to enforce patients' right to cross-border healthcare. This
      article investigates the current legal tools within the European Union on
      language gap in patient-provider communication and access to information on cross
      border healthcare entitlements. Moreover, it offers some possible solutions for
      the future.

PMID- 29210252
TI  - Property, Control and Separated Human Biomaterials.
AB  - This article examines the relationship between the existence of control rights
      and property in separated human biomaterials. Much of the theory as to what
      constitutes property is examined and it is contended that Article 22 of the
      Convention on Human Rights and Biomedicine does not presuppose property in such
      materials. An analysis is undertaken of the case-law relating to control and
      property in sperm and embryos from the UK, Australia and the US and the
      shortcomings of utilising the property paradigm in these disputes are
      highlighted.

PMID- 29210253
TI  - Should Anthroposophic Medicinal Products Be Regulated in Europe?
AB  - European Commission's reports suggest that the European Union should address the
      status of anthroposophic products, i.e. products that are developed, manufactured
      and prescribed in accordance with the holistic approach on which anthroposophic
      medicine is based. Anthroposophic products cannot be placed as such on the
      European market because they cannot meet the marketing authorisation or even
      registration requirements set out by European or national pharmaceutical law.
      Yet, the 95-year European tradition and good safety profile of anthroposophic
      products justify giving them an easier access to market. Such access can result
      from specific rules on anthroposophic products, but can be more efficiently
      achieved by encouraging the Member States to better apply the existing rules on
      marketing authorisation procedures or on registration of homeopathic and
      traditional herbal medicinal products, or by including anthroposophic substances,
      manufacturing methods or uses in monographs.

PMID- 29210254
TI  - Developing a Legal Framework for Advance Healthcare Planning: Comparing England &
      Wales and Ireland.
AB  - This article examines the legislative frameworks for advance healthcare planning
      in England & Wales (the Mental Capacity Act 2005) and in Ireland (the Assisted
      Decision-Making (Capacity) Act 2015), undertaking a comparative analysis of each
      measure, with particular focus on the detail of the approaches taken. It is only
      through this kind of detailed focus that the normative choices made by
      legislation can fully be understood and evaluated. The article argues that, in
      several respects, possibly because the drafters were able to reflect lessons
      learned from other jurisdictions, the Assisted Decision-Making (Capacity) Act
      2015 provides a more rounded and complete form of advance healthcare planning
      than that provided by the Mental Capacity Act. This is on the basis that it
      provides more protection for patient choice; better potential for delivery on the
      choices made; and a more appropriate balance between formalities and
      enforceability.

PMID- 29210255
TI  - The Legalisation of Gamete Donation in Italy.
AB  - Since 2004, the regulation of assisted reproduction in Italy has undergone
      substantial reform as an effect of key judicial intervention. Limitations on
      embryo production, screening and transfer, the prohibition against engaging in
      preimplantation genetic diagnosis (PGD) and embryo selection, and the ban on
      gamete donation have all been removed by courts. In this article, I discuss how
      judicial intervention has improved the ability of Italian couples to access
      assisted reproduction technologies (ARTs), and how the expansion of reproductive
      rights is, however, still incomplete. In particular, I discuss the challenges in
      implementing the liberalisation of gamete donation, and identify the practical,
      political and cultural reasons for limited access to gamete donation. I also
      discuss the future of the prohibitions and restrictions that still exist in Law
      40/2004.

PMID- 29210256
TI  - European Court of Human Rights.

PMID- 29210257
TI  - New EU Rules for In Vitro Diagnostic Genetic Tests, a First Step in the Right
      Direction.

PMID- 29210258
TI  - Genetic Discrimination: A Case for a European Legislative Response?
AB  - With rapid scientific and technological advances, a new genetic era is emerging.
      However, these advances raise ethical and legal issues, particularly genetic
      discrimination, that may threaten advancing science in the absence of appropriate
      regulation. There is currently no concrete legislative position in this area at
      EU level, but rather a patchwork of diverging legislative approaches amongst
      Member States. Genetic discrimination has been singled out as an area of reform
      in Europe as evidenced, for example in EU Charter of Fundamental Rights, Article
      21.1 prohibiting discrimination based on 'genetic features.' The United Nations
      Convention on the Rights of Persons with Disabilities also informs this debate
      and may spur legislative action. From a transatlantic perspective, the United
      States' federal legislation (Genetic Information Non Discrimination Act) is
      noteworthy. Considering scientific and technological developments, the rights at
      stake and the various regulatory benchmarks, this paper explores the regulation
      of genetic information in the EU.

PMID- 29210259
TI  - Preimplantation Genetic Diagnosis: The Situation in France and in Other European
      Countries.
AB  - Preimplantation genetic diagnosis (PGD) relates exclusively to in vitro
      fertilisation techniques (IVF) that aim to prevent transmission of a serious
      genetic abnormality to the child. The genetic characteristics of the embryo
      created through IVF are analysed, and only the embryos free of the genetic
      abnormality are implanted in the womb. Performed worldwide since 1990, this
      technique has raised many legal and ethical debates due to the very wide
      variations of lawgiving between countries. This is shown by the report of the
      UNESCO IBC (2003), which described the techniques and the issues raised by
      preimplantation genetic diagnosis. In this article, the authors present the
      differences between prenatal diagnosis and preimplantation genetic diagnosis, the
      French legislation, then the range of legislation in Europe and finally the
      position of the European Court of Human Rights which sanctioned Italy and Latvia
      for refusing access to PGD.

PMID- 29210260
TI  - "Better Not to Know?": Justifiable Limits on the Right to Information in the
      Realm of DTC Genetic Testing. An Analysis of the European and Spanish Legal
      Framework.
AB  - The rapid advance of genetics increases the availability in the market of
      different genetic tests, which can be acquired directly by consumers without the
      intermediation of a healthcare professional. Both the European and the Spanish
      legal framework have restricted the access to these direct-to-consumer (DTC)
      genetic tests on the grounds of different reasons, such as the protection of
      consumers or the preservation of public health. The present article discusses
      these legal restrictions under the light of the right to information.

PMID- 29210261
TI  - European Court of Human Rights.

PMID- 29210262
TI  - Modulation of Manganite Nanofilm Properties Mediated by Strong Influence of
      Strontium Titanate Excitons.
AB  - Hole-doped perovskite manganites have attracted much attention because of their
      unique optical, electronic, and magnetic properties induced by the interplay
      between spin, charge, orbital, and lattice degrees of freedom. Here, a
      comprehensive investigation of the optical, electronic, and magnetic properties
      of La0.7Sr0.3MnO3 thin films on SrTiO3 (LSMO/STO) and other substrates is
      conducted using a combination of temperature-dependent transport, spectroscopic
      ellipsometry, X-ray absorption spectroscopy, and X-ray magnetic circular
      dichroism. A significant difference in the optical property of LSMO/STO that
      occurs even in thick (87.2 nm) LSMO/STO from that of LSMO on other substrates is
      discovered. Several excitonic features are observed in thin film nanostructure
      LSMO/STO at ~4 eV, which could be attributed to the formation of anomalous
      charged excitonic complexes. On the basis of the spectral weight transfer
      analysis, anomalous excitonic effects from STO strengthen the electronic
      correlation in LSMO films. This results in the occurrence of optical spectral
      changes related to the intrinsic Mott-Hubbard properties in manganites. We find
      that while lattice strain from the substrate influences the optical properties of
      the LSMO thin films, the coexistence of strong electron-electron (e-e) and
      electron-hole (e-h) interactions which leads to the resonant excitonic effects
      from the substrate plays a much more significant role. Our result shows that the
      onset of anomalous excitonic dynamics in manganite oxides may potentially
      generate new approaches in manipulating exciton-based optoelectronic
      applications.

PMID- 29210263
TI  - Quasi 2D Mesoporous Carbon Microbelts Derived from Fullerene Crystals as an
      Electrode Material for Electrochemical Supercapacitors.
AB  - Fullerene C60 microbelts were fabricated using the liquid-liquid interfacial
      precipitation method and converted into quasi 2D mesoporous carbon microbelts by
      heat treatment at elevated temperatures of 900 and 2000  degrees C. The carbon
      microbelts obtained by heat treatment of fullerene C60 microbelts at 900  degrees
      C showed excellent electrochemical supercapacitive performance, exhibiting high
      specific capacitances ca. 360 F g-1 (at 5 mV s-1) and 290 F g-1 (at 1 A g-1)
      because of the enhanced surface area and the robust mesoporous framework
      structure. Additionally, the heat-treated carbon microbelt showed good rate
      performance, retaining 49% of capacitance at a high scan rate of 10 A g-1. The
      carbon belts exhibit super cyclic stability. Capacity loss was not observed even
      after 10 000 charge/discharge cycles. These results demonstrate that the quasi 2D
      mesoporous carbon microbelts derived from a pi-electron-rich carbon source,
      fullerene C60 crystals, could be used as a new candidate material for
      electrochemical supercapacitor applications.

PMID- 29210264
TI  - Morphology and Surface Reactivity Relationship in the Li1+xMn2-xO4 Spinel with x
      = 0.05 and 0.10: A Combined First-Principle and Experimental Study.
AB  - This article focuses on the surface reactivity of two spinel samples with
      different stoichiometries and crystal morphologies, namely Li1+xMn2-xO4 with x =
      0.05 and 0.10. LiMn2O4 compounds are good candidates as positive electrode of
      high-power lithium-ion batteries for portable devices. The samples were
      investigated using both experimental and theoretical approaches. On the
      experimental point of view, they were characterized in depth from X-ray
      diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy
      (XPS) analyses. Then, the reactivity was investigated through the adsorption of
      (SO2) gaseous probes, in controlled conditions, followed by XPS characterization.
      First-principle calculations were conducted simultaneously to investigate the
      electronic properties and the reactivity of relevant surfaces of an ideal LiMn2O4
      material. The results allow us to conclude that the reactivity of the samples is
      dominated by an acido-basic reactivity and the formation of sulfite species.
      Nonetheless, on the x = 0.05 sample, both sulfite and sulfate species are
      obtained, the later, in lesser extent, corresponding to a redox reactivity.
      Combining experimental and theoretical results, this redox reactivity could be
      associated with the presence of a larger quantity of Mn4+ cations on the last
      surface layers of the material linked to a specific surface orientation.

PMID- 29210265
TI  - Characterizing the Switching Transitions of an Adsorbed Peptide by Mapping the
      Potential Energy Surface.
AB  - Peptide adsorption occurs across technology, medicine, and nature. The functions
      of adsorbed peptides are related to their conformation. In the past, molecular
      simulation methods such as molecular dynamics have been used to determine key
      conformations of adsorbed peptides. However, the transitions between these
      conformations often occur too slowly to be modeled reliably by such methods. This
      means such transitions are less well understood. In the study reported here,
      discrete path sampling is used for the first time to study the potential energy
      surface of an adsorbed peptide (polyalanine) and the transition pathways between
      various stable adsorbed conformations that have been identified in prior work by
      two of the authors [ Mijajlovic , M. ; Biggs , M. J. J. Phys. Chem. C 2007 , 111
      , 15839 - 15847 ]. Mechanisms for the switching of adsorbed polyalanine between
      the stable conformations are elucidated along with the energetics of these
      switches.

PMID- 29210266
TI  - High-Speed Atomic Force Microscopy Reveals the Inner Workings of the MinDE
      Protein Oscillator.
AB  - The MinDE protein system from E. coli has recently been identified as a minimal
      biological oscillator, based on two proteins only: The ATPase MinD and the ATPase
      activating protein MinE. In E. coli, the system works as the molecular ruler to
      place the divisome at midcell for cell division. Despite its compositional
      simplicity, the molecular mechanism leading to protein patterns and oscillations
      is still insufficiently understood. Here we used high-speed atomic force
      microscopy to analyze the mechanism of MinDE membrane association/dissociation
      dynamics on isolated membrane patches, down to the level of individual point
      oscillators. This nanoscale analysis shows that MinD association to and
      dissociation from the membrane are both highly cooperative but mechanistically
      different processes. We propose that they represent the two directions of a
      single allosteric switch leading to MinD filament formation and depolymerization.
      Association/dissociation are separated by rather long apparently silent periods.
      The membrane-associated period is characterized by MinD filament multivalent
      binding, avidity, while the dissociated period is defined by seeding of
      individual MinD. Analyzing association/dissociation kinetics with varying MinD
      and MinE concentrations and dependent on membrane patch size allowed us to
      disentangle the essential dynamic variables of the MinDE oscillation cycle.

PMID- 29210267
TI  - Ultrafast Photodynamics of Glucose.
AB  - We have investigated the photodynamics of beta-d-glucose employing our field
      induced surface-hopping (FISH) method, which allows us to simulate the coupled
      electron-nuclear dynamics, explicitly including nonadiabatic effects and light
      induced excitation. Our results reveal that from the initially populated S1 and
      S2 states, glucose returns nonradiatively to the ground state within about 200
      fs. This takes place mainly via conical intersections (CIs), whose geometries in
      most cases involve the elongation of a single O-H bond, whereas in some
      instances, ring-opening due to dissociation of a C-O bond is observed.
      Experimentally, excitation to a distinct excited electronic state is improbable
      due to the presence of a dense manifold of states bearing similar oscillator
      strengths. Our FISH simulations, explicitly including a UV laser pulse of 6.43 eV
      photon energy, reveal that after initial excitation, the population is almost
      equally spread over several close-lying electronic states. This is followed by a
      fast nonradiative decay on the time scale of 100-200 fs, with the final return to
      the ground state proceeding via the S1 state through the same types of CIs as
      observed in the field-free simulations.

PMID- 29210268
TI  - Correction to "Limits of Carrier Diffusion in n-Type and p-Type CH3NH3PbI3
      Perovskite Single Crystals".

PMID- 29210269
TI  - Single or Synergistic Kinetic Resolutions of Chiral Allylalanes: Two
      Complementary Routes for the Asymmetric Synthesis of Syn Homoallylamines.
AB  - Two strategies based on kinetic resolution(s) of chiral alanes and providing
      enantioenriched syn homoallylamines are reported. The first implies a single
      kinetic resolution of the alane using camphor; the second requires two sequential
      kinetic resolutions using the synergistic combination of (-)-camphor/(R)-tert
      butylsulfinamide-derived imines. This syn selectivity, specific to the use of
      allyaluminum, opens the way to the preparation of valuable building blocks as
      illustrated by the synthesis of (+)-epilupinamine.

PMID- 29210270
TI  - Morphology Control of Carbon-Free Spinel NiCo2O4 Catalysts for Enhanced
      Bifunctional Oxygen Reduction and Evolution in Alkaline Media.
AB  - Spinel NiCo2O4 is considered a promising precious metal-free catalyst that is
      also carbon-free for oxygen electrocatalysis. Current efforts mainly focus on
      optimal chemical doping and substituent to tune its electronic structures for
      enhanced activity. Here, we study its morphology control and elucidate the
      morphology-dependent catalyst performance for bifunctional oxygen reduction
      reaction (ORR) and oxygen evolution reaction (OER). Three types of NiCo2O4
      catalysts with significantly distinct morphologies were prepared using temple
      free, Pluronic-123 (P-123) soft, and SiO2 hard templates, respectively, via
      hydrothermal methods followed by calcination. Whereas the hard-template yields
      spherelike dense structures, soft-template assists the formation of a unique
      nanoneedle cluster assembly containing abundant meso- and macropores.
      Furthermore, the effect of morphology of NiCo2O4 on their corresponding
      bifunctional catalytic performance was systematically investigated. The
      flowerlike nanoneedle assembly NiCo2O4 catalyst via the soft-template method
      exhibited the highest catalytic activity and stability for both ORR and OER. In
      particular, it exhibited an onset and half-wave potentials of 0.94 and 0.82 V
      versus reversible hydrogen electrode, respectively, for the ORR in alkaline
      media. Although it is still inferior to Pt, the NiCo2O4 represents one of the
      best ORR catalyst compared to other reported carbon-free oxides. Meanwhile,
      remarkable OER activity and stability were achieved with an onset potential of
      1.48 V and a current density of 15 mA/cm2 at 1.6 V, showing no activity loss
      after 20 000 potential cycles (0-1.9 V). The demonstrated stability is even
      superior to Ir for the OER. The morphology-controlled approach provides an
      effective solution to create a robust three-dimensional architecture with
      increased surface areas and enhanced mass transfer. Importantly, the soft
      template can yield a high degree of spinel crystallinity with ideal
      stoichiometric ratios between Ni and Co, thus promoting structural integrity with
      enhanced electrical conductivity and catalytic properties.

PMID- 29210271
TI  - Ultrasensitive Detection of Cancer Cells Combining Enzymatic Signal Amplification
      with an Aerolysin Nanopore.
AB  - Sensitive detection of cancer cells at extremely low concentrations would greatly
      facilitate the screening and early diagnosis of cancer. Herein, we present a
      novel nanopore-based strategy for ultrasensitive detection of Ramos cells (human
      Burkitt's lymphoma cells), by combining the enzymatic signal amplification with
      an aerolysin nanopore sensor. In this assay, an aptamer for Ramos cells was
      prehybridized with a short complementary DNA. The presence of target cells causes
      the target-aptamer complex to unwind to free the complementary DNA, which would
      subsequently trigger the enzymatic cycling amplification. This process eventually
      generated a large number of output DNA, which could quantitatively produce
      characteristic current events when translocated through aerolysin. The proposed
      method exhibits excellent sensitivity, and as few as 5 Ramos cells could be
      detected. With good selectivity, the approach can allow for the determination of
      cancer cells in human serum, offering a powerful tool for biomedical research and
      clinical diagnosis.

PMID- 29210272
TI  - Facile Electrochemical Synthesis of 2D Monolayers for High-Performance Thin-Film
      Transistors.
AB  - In this paper, we report high-performance monolayer thin-film transistors (TFTs)
      based on a variety of two-dimensional layered semiconductors such as MoS2, WS2,
      and MoSe2 which were obtained from their corresponding bulk counterparts via an
      anomalous but high-yield and low-cost electrochemical corrosion process, also
      referred to as electro-ablation (EA), at room temperature. These monolayer TFTs
      demonstrated current ON-OFF ratios in excess of 107 along with ON currents of 120
      MUA/MUm for MoS2, 40 MUA/MUm for WS2, and 40 MUA/MUm for MoSe2 which clearly
      outperform the existing TFT technologies. We found that these monolayers have
      larger Schottky barriers for electron injection compared to their multilayer
      counterparts, which is partially compensated by their superior electrostatics and
      ultra-thin tunnel barriers. We observed an Anderson type semiconductor-to-metal
      transition in these monolayers and also discussed possible scattering mechanisms
      that manifest in the temperature dependence of the electron mobility. Finally,
      our study suggests superior chemical stability and electronic integrity of
      monolayers even after being exposed to extreme electro-oxidation and corrosion
      processes which is promising for the implementation of such TFTs in harsh
      environment sensing. Overall, the EA process proves to be a facile synthesis
      route offering higher monolayer yields than mechanical exfoliation and lower cost
      and complexity than chemical vapor deposition methods.

PMID- 29210273
TI  - Covalently Attached Antimicrobial Surfaces Using BODIPY: Improving Efficiency and
      Effectiveness.
AB  - The development of photoactivated antimicrobial surfaces that kill pathogens
      through the production of singlet oxygen has proved very effective in recent
      years, with applications in medical devices and hospital touch surfaces, to
      improve patient safety and well being. However, many of these surfaces require a
      swell-encapsulation-shrink strategy to incorporate the photoactive agents in a
      polymer matrix, and this is resource intensive, given that only the surface
      fraction of the agent is active against bacteria. Furthermore, there is a risk
      that the agent will leach from the polymer and thus raises issues of
      biocompatibility and patient safety. Here, we describe a more efficient method of
      fabricating a silicone material with a covalently attached monolayer of
      photoactivating agent that uses heavy-atom triplet sensitization for improved
      singlet oxygen generation and corresponding antimicrobial activity. We use boron
      dipyrromethane with a reactive end group and incorporated Br atoms, covalently
      attached to poly(dimethylsiloxane). We demonstrate the efficacy of this material
      in producing singlet oxygen and killing Staphylococcus aureus and suggest how it
      might be easily modifiable for future antimicrobial surface development.

PMID- 29210274
TI  - Synthesis of N,S-Heterocycles and Dithiocarbamates by the Reaction of
      Dithiocarbamic Acids and S-Alkyl Dithiocarbamates with Nitroepoxides.
AB  - A facile and efficient procedure for the synthesis of substituted thiazole-2(3H)
      thiones and thiazolidine-2-thiones by the reaction of primary amines, carbon
      disulfide, and nitroepoxides is described. By using secondary amines in this
      protocol, the corresponding dithiocarbamate-substituted phenyl-2-propanones were
      prepared in excellent yields. In addition, substituted thiazoles and 1
      (alkylthio)-1-phenylpropan-2-ones were prepared in reactions of S-alkyl
      dithiocarbamates and nitroepoxides.

PMID- 29210275
TI  - Sequestration of Antimony on Calcite Observed by Time-Resolved Nanoscale Imaging.
AB  - Antimony, which has damaging effects on the human body and the ecosystem, can be
      released into soils, ground-, and surface waters either from ore minerals that
      weather in near surface environments, or due to anthropogenic releases from waste
      rich in antimony, a component used in batteries, electronics, ammunitions,
      plastics, and many other industrial applications. Here, we show that dissolved Sb
      can interact with calcite, a widespread carbonate mineral, through a coupled
      dissolution-precipitation mechanism. The process is imaged in situ, at room
      temperature, at the nanometer scale by using an atomic force microscope equipped
      with a flow-through cell. Time-resolved imaging allowed following the coupled
      process of calcite dissolution, nucleation of precipitates at the calcite surface
      and growth of these precipitates. Sb(V) forms a precipitate, whereas Sb(III)
      needs to be oxidized to Sb(V) before being incorporated in the new phase.
      Scanning-electron microscopy and Raman spectroscopy allowed identification of the
      precipitates as two different calcium-antimony phases (Ca2Sb2O7). This coupled
      dissolution-precipitation process that occurs in a boundary layer at the calcite
      surface can sequester Sb as a solid phase on calcite, which has environmental
      implications as it may reduce the mobility of this hazardous compound in soils
      and groundwaters.

PMID- 29210276
TI  - Direct Carboxylation of the Diazo Group ipso-C(sp2)-H bond with Carbon Dioxide:
      Access to Unsymmetrical Diazomalonates and Derivatives.
AB  - The direct carboxylation of the ipso-C(sp2)-H bond of a diazo compound with
      carbon dioxide under mild reaction conditions is described. This method is
      transition-metal-free, uses a weak base, and proceeds at ambient temperature
      under atmospheric pressure in carbon dioxide. The carboxylation exhibits high
      reactivity and is amenable to subsequent diversification. A series of
      unsymmetrical 1,3-diester/keto/amide diazo compounds are obtained with moderate
      to excellent yields (up to 99%) with good functional group compatibility.

PMID- 29210277
TI  - Catalytic Enantioselective Synthesis of (-)-Podophyllotoxin.
AB  - The first catalytic enantioselective total synthesis of (-)-podophyllotoxin is
      accomplished by a challenging organocatalytic cross-aldol Heck cyclization and
      distal stereocontrolled transfer hydrogenation in five steps from three
      aldehydes. Reversal of selectivity in hydrogenation led to the syntheses of other
      stereoisomers from the common precursor.

PMID- 29210278
TI  - Decellularized Liver Matrix-Modified Cryogel Scaffolds as Potential Hepatocyte
      Carriers in Bioartificial Liver Support Systems and Implantable Liver Constructs.
AB  - Recent progress in the use of decellularized organ scaffolds as regenerative
      matrices for tissue engineering holds great promise in addressing the issue of
      donor organ shortage. Decellularization preserves the mechanical integrity,
      composition, and microvasculature critical for zonation of hepatocytes in the
      liver. Earlier studies have reported the possibility of repopulating
      decellularized matrices with hepatic cell lines or stem cells to improve liver
      regeneration. In this work, we study the versatility of the decellularized liver
      matrix as a substrate coating of three-dimensional cryogel scaffolds. The coated
      cryogels were analyzed for their ability to maintain hepatic cell growth and
      functionality in vitro, which was found to be significantly better than the
      uncoated cryogel scaffolds. The decellularized liver matrix-coated cryogel
      scaffolds were evaluated for their potential application as a cell-loaded
      bioreactor for bioartificial liver support and as an implantable liver construct.
      Extracorporeal connection of the coated cryogel bioreactor to a liver failure
      model showed improvement in liver function parameters. Additionally, offline
      clinical evaluation of the bioreactor using patient-derived liver failure plasma
      showed its efficacy in improving liver failure conditions by approximately 30
      60%. Furthermore, implantation of the decellularized matrix-coated cryogel showed
      complete integration with the native tissue as confirmed by hematoxylin and eosin
      staining of tissue sections. HepG2 cells and primary human hepatocytes seeded in
      the coated cryogel scaffolds implanted in the liver failure model maintained
      functionality in terms of albumin synthesis and cytochrome P450 activity post 2
      weeks of implantation. In addition, a 20-60% improvement in liver function
      parameters was observed post implantation. These results, put together, suggest a
      possibility of using the decellularized matrix-coated cryogel scaffolds for liver
      tissue engineering applications.

PMID- 29210279
TI  - Erythrocyte-Membrane-Coated Prussian Blue/Manganese Dioxide Nanoparticles as H2O2
      Responsive Oxygen Generators To Enhance Cancer Chemotherapy/Photothermal Therapy.
AB  - Because of the nontargeting release of anticancer drugs, conventional
      chemotherapy results in serious side effects and poor therapeutic outcomes. In
      addition, hypoxia situation in the tumor microenvironment also promotes the
      growth and metastasis of tumors. Multifunctional nanocarriers with stimuli
      activation and hypoxia-relieving properties can help overcome some of these
      limitations. In this study, we have constructed a nanocarrier which is named PBMn
      DOX@RBC. A Prussian blue/manganese dioxide (PBMn) nanoparticle is used as an
      oxygen precursor or catalyzer for H2O2 activation, and a red blood cell (RBC)
      membrane is used to increase the loading capacity of doxorubicin (DOX) and
      prolong the circulation time in vivo. H2O2 is overproduced in tumor tissues and
      tumor cells. It can be used as a stimulus to activate drug release. In the
      presence of H2O2, the hypoxia inside the tumors is relieved by the administration
      of PBMn-DOX@RBC. The generated oxygen disrupts the RBC coated on the surface of
      PBMn, which accelerates the release of DOX. RBCs also prolong the circulation
      time of the nanometer system in vivo. By combining the photothermal therapy (PTT)
      and chemotherapy, the tumor growth inhibition mediated by PBMn-DOX@RBC is further
      enhanced. PBMn-DOX@RBC fulfills the demands to relieve tumor hypoxia and enhance
      cancer chemotherapy/PTT.

PMID- 29210280
TI  - Quantifying the Primary Emissions and Photochemical Formation of Isocyanic Acid
      Downwind of Oil Sands Operations.
AB  - Isocyanic acid (HNCO) is a known toxic species and yet the relative importance of
      primary and secondary sources to regional HNCO and population exposure remains
      unclear. Off-road diesel fuel combustion has previously been suggested to be an
      important regional source of HNCO, which implies that major industrial facilities
      such as the oil sands (OS), which consume large quantities of diesel fuel, can be
      sources of HNCO. The OS emissions of nontraditional toxic species such as HNCO
      have not been assessed. Here, airborne measurements of HNCO were used to estimate
      primary and secondary HNCO for the oil sands. Approximately 6.2 +/- 1.1 kg hr-1
      was emitted from off-road diesel activities within oil sands facilities, and an
      additional 116-186 kg hr-1 formed from the photochemical oxidation of diesel
      exhaust. Together, the primary and secondary HNCO from OS operations represent a
      significant anthropogenic HNCO source in Canada. The secondary HNCO downwind of
      the OS was enhanced by up to a factor of 20 relative to its primary emission, an
      enhancement factor significantly greater than previously estimated from
      laboratory studies. Incorporating HNCO emissions and formation into a regional
      model demonstrated that the HNCO levels in Fort McMurray (~10-70 km downwind of
      the OS) are controlled by OS emissions; > 50% of the monthly mean HNCO arose from
      the OS. While the mean HNCO levels in Fort McMurray are predicted to be below the
      1000 pptv level associated with potential negative health impacts, (~25 pptv in
      August-September), an order of magnitude increase in concentration is predicted
      (250-600 pptv) when the town is directly impacted by OS plumes. The results here
      highlight the importance of obtaining at-source HNCO emission factors and
      advancing the understanding of secondary HNCO formation mechanisms, to assess and
      improve HNCO population exposure predictions.

PMID- 29210281
TI  - Characterization of the Rhodococcus sp. MK1 strain and its pilot application for
      bioremediation of diesel oil-contaminated soil.
AB  - Petroleum hydrocarbons and derivatives are widespread contaminants in both
      aquifers and soil, their elimination is in the primary focus of environmental
      studies. Microorganisms are key components in biological removal of pollutants.
      Strains capable to utilize hydrocarbons usually appear at the contaminated sites,
      but their metabolic activities are often restricted by the lack of nutrients
      and/or they can only utilize one or two components of a mixture. We isolated a
      novel Rhodococcus sp. MK1 strain capable to degrade the components of diesel oil
      simultaneously. The draft genome of the strain was determined and besides the
      chromosome, the presence of one plasmid could be revealed. Numerous routes for
      oxidation of aliphatic and aromatic compounds were identified. The strain was
      tested in ex situ applications aiming to compare alternative solutions for
      microbial degradation of hydrocarbons. The results of bioaugmentation and
      biostimulation experiments clearly demonstrated that - in certain cases - the
      indigenous microbial community could be exploited for bioremediation of oil
      contaminated soils. Biostimulation seems to be efficient for removal of aged
      contaminations at lower concentration range, whereas bioaugmentation is necessary
      for the treatment of freshly and highly polluted sites.

PMID- 29210282
TI  - Neuropsychiatric Profile in Early Versus Late Onset Alzheimer's Disease.
AB  - BACKGROUND: The aim of this study was to investigate the frequency and severity
      of neuropsychiatric symptoms (NPS) in patients with early onset Alzheimer's
      disease (EAOD) and late onset AD (LOAD). METHODS: Patients were selected from a
      specialized memory outpatient clinic. The Mini-Mental State Examination, the
      Neuropsychiatric Inventory (NPI), and the Global Deterioration Scale results were
      analyzed. RESULTS: By comparing EOAD (n = 35) and LOAD (n = 35) patients, no
      significant differences were found in clinical or demographic variables, matched
      for sex, education, and disease severity. There were no differences between
      groups in total NPI frequency or severity scores. The most common NPS were
      irritability, apathy, anxiety, and depression. We found an association of NPI
      scores with disease severity and duration, which was more specific in patients
      with LOAD and was also associated with the presence of delusions and
      hallucinations. CONCLUSION: Despite subtle differences, NPS is considered
      important in the assessment of patients with AD, regardless of the age of onset.

PMID- 29210283
TI  - The Contribution of Supplementary Tests in the Differential Diagnosis of
      Dementia.
AB  - INTRODUCTION: Supplementary tests are part of the clinical approach to diagnose
      cognitive impairment. We aimed to determine the role of supplementary
      examinations, except for biomarkers, on diagnostic stability of dementia over
      time and to identify reversible dementias. METHODS: We identified 432 patients
      with dementia who performed 2 clinical evaluations and the supplementary
      examinations recommended by the American Academy of Neurology in a follow-up
      period of 1 year. RESULTS: In this sample, 110 (24.5%) patients changed their
      diagnosis at 1-year follow-up for the appearance of vascular cognitive impairment
      than the initial diagnosis, due to the neuroimaging. Concerning the reversible
      dementias, depression was the major differential diagnosis, detected in 13 (81%)
      of the 16 patients with cognitive improvement. CONCLUSION: Therefore, regarding
      the supplementary examinations only neuroimaging and the depression triage were
      relevant for clinical practice regarding the differential diagnosis of dementia.

PMID- 29210284
TI  - Can Persistence With Cholinesterase Inhibitor Treatment Lower Mortality and
      Health-Care Costs Among Patients With Alzheimer's Disease? A Population-Based
      Study in Taiwan.
AB  - Although cholinesterase inhibitors (ChEIs) have been proved to help reduce
      cognitive deterioration in patients with Alzheimer's disease (AD), their effects
      on survival remain inconclusive. This study aims to assess the effects of the
      persistent use of ChEIs on the risk of mortality in patients with AD. This
      population-based cohort study included 8614 patients having AD with ChEI
      prescription from 2002 to 2006 and followed until 2010. Kaplan-Meier curves and
      hazard ratios (HRs) of mortality were estimated in association with ChEI
      treatment duration and adherence. The average annual mortality rate per 100
      person-years was 9.2 for the short-duration group (discontinued < 1 year) and 7.2
      for the long-duration group (discontinued >= 2 years). Compared to the short
      duration group, the long-duration group had a lower mortality (HR = 0.76, 95%
      confidence interval: 0.69-0.84) and shorter annual inpatient days. But the annual
      health-care costs did not differ significantly between the 2 groups.

PMID- 29210285
TI  - New tetralone derivatives from the leaves of Cyclocarya paliurus.
AB  - Two new tetralone derivatives, named cyclopalosides A (1) and B (2), were
      isolated from the leaves of Cyclocarya paliurus by column chromatography on
      silica gel, reversed-phase C18 silica gel and preparative HPLC. Their chemical
      structures were established on the basis of extensive analyses of spectroscopic
      data. Their structural characteristic is tetralone glycoside with a caffeoyl
      unit. The antioxidant activities of compound 1 were evaluated by using hydroxyl,
      superoxide anion, and DPPH radical scavenging assay.

PMID- 29210286
TI  - Morality in clinical space: treatment of youngsters with functional somatic
      symptoms in a Western clinical context.
AB  - This paper explores the moral implications of treatment of young people with
      functional somatic symptoms. Based on an ethnographic field study at a Danish
      pain clinic for youngsters (age 8 to 18), the paper seeks to unearth the
      cultural, moral values that clinical practice steers by and upholds, and the
      implications this has for the assessment and management of ill body-selves.
      Through an exposition of the general practice of the clinic and an investigation
      of two specific cases of youngsters, it is found that the assessment of symptoms
      and selves and the goals of treatment are informed by cultural ideals of 'the
      good self' and 'the good life' in which agency and work ethic - both pertaining
      to the notion of individual responsibility - figure as prevalent virtues. The
      study underpins the findings of other researchers who have found that ideals of
      individual autonomy and responsibility for own life and health permeate the
      Western health care system and the discourses of ill individuals. The
      contribution of this article is to portray in ethnographic detail how such a
      cultural ethics manifests in practice and what implications this have for the
      treatment of young people with functional symptoms at a specific location and in
      specific cases. The two cases illustrate that the underlying norms and values can
      give rise to very different moral assessments of symptoms and selves within the
      same diagnostic category.

PMID- 29210288
TI  - Efficacy and effectiveness of valsartan/amlodipine and
      valsartan/amlodipine/hydrochlorothiazide in hypertension: randomized controlled
      versus observational studies.
AB  - OBJECTIVE: The aim of this post-hoc analysis was to compare the results from
      randomized controlled trials (RCTs) and real-world evidence (RWE) studies of
      valsartan/amlodipine (Val/Aml) and valsartan/amlodipine/hydrochlorothiazide
      (Val/Aml/HCTZ) in patients with uncontrolled hypertension (>140/90 mmHg).
      METHODS: Data was pooled from 15 RCTs (N = 5542) and 8 RWE studies (N = 1397) for
      Val/Aml; and 2 RCTs (N = 804) and 5 RWE studies (N = 9380) for Val/Aml/HCTZ.
      Patients who received Val/Aml (80/5, 160/5, 160/10, 320/5, or 320/10 mg),
      Val/Aml/HCTZ (160/5/12.5, 160/5/25, 160/10/12.5, 160/10/25, or 320/10/25 mg) or
      placebo were considered for this analysis. Only patients with both baseline and
      follow-up assessment within 60-90 days after baseline had been included in the
      analysis. Patients with missing values were excluded from the analysis. Using
      fitted linear mixed-effects model and random factors, treatment interactions and
      study design with mean sitting systolic blood pressure (msSBP), diastolic BP
      (msDBP) and pulse pressure (msPP) reductions from baseline to Week 8-12 of
      treatment were compared. RESULTS: Baseline demographics and patient
      characteristics were comparable between RCT and RWE datasets and within Val/Aml
      and Val/Aml/HCTZ treatment groups. In both RCT and RWE studies, least-squares
      mean (LSM) reduction in msSBP/msDBP and msPP from baseline were significant (p <
      .05) across all dosages. The efficacy of Val/Aml in RCTs was statistically
      significantly greater than in RWE studies for msSBP/msDBP (-23.1/-13.8 vs. -17.9/
      9.1 mmHg) but the difference was non-significant for msPP (-8.6 vs. -9.3 mmHg; p
      = .77). For Val/Aml/HCTZ, no direct comparison was available but a similar trend
      was observed. The difference observed for msSBP and msDBP may be due to routine
      practice setting, larger populations may have more confounders and different
      behaviors towards treatment adherence. CONCLUSION: These findings demonstrate
      that the efficacy of Val/Aml and Val/Aml/HCTZ in RCTs was more pronounced
      compared with their effectiveness in RWE studies in different ethnic populations
      although the overall benefit was not different.

PMID- 29210289
TI  - Retraction.

PMID- 29210287
TI  - Dexmedetomidine protects against oxygen-glucose deprivation/reoxygenation injury
      induced apoptosis via the p38 MAPK/ERK signalling pathway.
AB  - Objective To investigate the protective effects of dexmedetomidine (DEX) in
      oxygen-glucose deprivation/reoxygenation (OGD/R) injury, which is involved in a
      number of ischaemic diseases. Methods An in vitro OGD/R injury model was
      generated using mouse Neuro 2A neuroblastoma (N2A) cells. Different
      concentrations of DEX were administrated to OGD/R cells. CV-65 was used to
      inhibit p38 microtubule associated protein kinase/extracellular signal-regulated
      kinases (MAPK/ERK) signalling. Cell proliferation, cell cycle, apoptosis, and the
      levels of proteins related to p38 MAPK/ERK signalling and apoptosis were
      evaluated using Cell Counting Kit-8, flow cytometry, TdT-UTP nick end labelling
      and Western blot analysis, respectively. Results DEX treatment of OGD/R cells
      promoted cell survival and attenuated OGD/R-induced cell apoptosis. It also
      activated the p38 MAPK/ERK signalling pathway, increased the levels of Bcl-2, and
      decreased the levels of Bax and cleaved caspase-3. Treatment with the p38
      MAPK/ERK inhibitor CV-65 inhibited the activation of p38 MAPK/ERK and abrogated
      the DEX-induced effects on cell survival and apoptosis. Conclusions DEX protects
      N2A cells from OGD/R-induced apoptosis via the activation of the p38 MAPK/ERK
      signalling pathway. DEX might be an effective agent for the treatment of
      ischaemic diseases.

PMID- 29210290
TI  - Demographic and lifestyle factors that affect HbA1c awareness amongst type II
      diabetic patients in Trinidad.
AB  - OBJECTIVES: To determine the awareness of HbA1c values and correlate this with
      educational levels, dietary intake and physical activity in type II diabetic
      population of Trinidad. METHODS: Total of 222 type II diabetic subjects were
      assessed via questionnaire evaluating their demographics, type and duration of
      diabetes, type and frequency of glucose testing, dietary intake and physical
      activity. HbA1c data was coded as patients who were aware versus patients who
      were not aware. RESULTS: Of the respondents, 41.9% were aware of the term HbA1c
      while 58.1% were unaware. Statistically, there were positive correlations (p <
      .05) between HbA1c awareness and level of education received by type II diabetic
      patients as well as between HbA1c awareness and intensity of exercise performed
      (p< .05). However, the relationship between dietary breakfast choices and HbA1c
      awareness was not significant. CONCLUSIONS: A significant correlation was
      established between HbA1c awareness, intensity of exercise and the level of
      education obtained.

PMID- 29210291
TI  - Use of cerebral oxygen saturation and hemoglobin concentration to predict acute
      kidney injury after cardiac surgery.
AB  - Objective Acute kidney injury (AKI) is a common complication after cardiac
      surgery and is associated with significant morbidity and mortality. Near infrared
      spectroscopy (NIRS) is a noninvasive technique for real-time measurement of
      cerebral tissue oxygenation. The purpose of the present study was to evaluate the
      correlation of AKI with hemoglobin and regional cerebral oxygen saturation
      (rScO2) measured intraoperatively and postoperatively in patients undergoing
      cardiac surgery. Methods We retrospectively analyzed the prospectively collected
      data of 45 adult patients with normal renal function who underwent isolated
      coronary artery bypass grafting (CABG) from January 2014 to May 2014. Kidney
      injury was assessed according to the Acute Kidney Injury Network criteria. rScO2
      and hemoglobin were measured every hour intraoperatively and for the first 24
      hours postoperatively. Results The hemoglobin concentration and rScO2 were
      significantly lower in patients with than without AKI, and no linear trends were
      observed. No exact cut-off values were obtained. Conclusion This retrospective
      study shows that a lower rScO2 and hemoglobin concentration are correlated with
      AKI after CABG in patients with no peripheral vascular disease or recent
      myocardial infarction. We suggest that cerebral oximetry alone may predict
      postoperative AKI well.

PMID- 29210292
TI  - The role of LPD-nanoparticles containing recombinant major surface glycoprotein
      of Leishmania (rgp63) in protection against leishmaniasis in murine model.
AB  - CONTEXT: Leishmaniasis is a major public health problem. Despite numerous
      attempts, yet there is no effective vaccine against human leishmaniasis, mainly
      due to a lack of an effective vaccine delivery system as well as adjuvant.
      OBJECTIVE(S): The aim of this study was to evaluate the ability of recombinant
      glycoprotein 63 (rgp63) as a model of Leishmania antigen, entrapped in liposome
      polycation-DNA (LPD) complexes nanoparticles in inducing cell mediated immune
      (CMI) response and protecting against L. major in BALB/c mice. MATERIALS AND
      METHODS: To this end, the abundant leishmania promastigote cell surface
      glycoprotein, gp63, was entrapped in nano-sized LPD (CpG) particles, (LPD (CpG)
      rgp63), and BALB/c mice were immunized three times with either (LPD (CpG)-rgp63)
      or rgp63-CpG DNA or LPD (CpG) or free rgp63 and dextrose 5%. Various parameters
      including footpad thickness, splenic load of L. major parasites, rgp63-binding
      IgGs and also cytokine levels of rgp63-reactive T lymphocytes were then compared
      among different vaccinated animals. RESULTS: The lowest number of parasites in
      spleen, the higher levels of IgG2a after challenge infection, the minimal footpad
      swelling and high level of IFN-gamma secretion, all indicated that adjuvants and
      antigen-delivery systems are essential in modifying immune responses; as mice
      received LPD (CpG)-rgp63 induced immune response stronger than the other groups.
      CONCLUSIONS: This study demonstrates that LPD nanoparticle is a promising and
      adaptable delivery system which could be modified towards specific vaccine
      targets to induce a more potent immune response in combination with rgp63.

PMID- 29210293
TI  - Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in
      rats.
AB  - Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast
      cancer, prostate cancer and gastric cancer, but several side effects such as
      peripheral neurotoxicity could occur. The present study was designed to
      investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel
      induced peripheral neurotoxicity. Rats were randomly divided into three groups
      and treated for 4 weeks. Behavioral tests were conducted to measure the effects
      of PC on docetaxel-induced decreases in mechanical & thermal nociceptive
      threshold. Biochemical tests were conducted to measure the level of oxidative
      stress on sciatic nerve. Histopathological and immunohistochemical experiments
      were also conducted to assess neuronal damage and glial activation. PC treatment
      significantly attenuated docetaxel-induced changes in mechanical & thermal
      nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by
      increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide
      dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated
      docetaxel-induced neuronal damage and microglial activation in the sciatic nerve
      and spinal cord. Thus, PC showed protective effects against docetaxel-induced
      peripheral neurotoxicity. These effects may be attributed to its antioxidant
      properties and modulation of microglia.

PMID- 29210295
TI  - Chemical constituents of Oldenlandia pinifolia and their antiproliferative
      activities.
AB  - This study describes the chemical constituents of Oldenlandia pinifolia (Wall. Ex
      G. Don) Kuntze (synonym Hedyotis pinifolia Wall. Ex G. Don) and discusses their
      anti-proliferative activities. Thirteen compounds were isolated from the n
      hexane, ethyl acetate and n-butanol extracts of whole plants O. pinifolia by
      chromatography method. Their structures were elucidated using MS and NMR analysis
      and compared with reported data. They are three anthraquinones, a carotenoid, two
      triterpenes, four iridoid glycosides and three flavonoid glycosides. Among them,
      2-methyl-1,4,6-trihydroxy-anthraquinone is a new one, and three compounds were
      found for the first time in this genus. MTT assay resulted that the n-butanol
      extract and four isolated compounds inhibited the proliferation of chronic
      myelogenous leukaemia cells. The results from Hoechst 33343 staining and caspase
      3-inducing exhibited that those four tested compounds induced apoptosis and
      activated caspase 3 (p < 0.05). One of them, isorhamnetin-3-O-beta-rutinoside
      showed the most activity with IC50 value of 394.68 +/- 25.12 MUM.

PMID- 29210294
TI  - Current and future therapeutic approaches for osteosarcoma.
AB  - INTRODUCTION: Current treatment of osteosarcoma includes surgical resection of
      all gross disease in conjunction with systemic chemotherapy to control micro
      metastatic disease. This yields a 5-year event free survival (EFS) of
      approximately 70% for patients with localized osteosarcoma while patients with
      metastatic or recurrent disease fare poorly with overall survival rates of less
      than 20%. Areas covered: This review outlines the current and future approach
      towards the treatment of osteosarcoma. A literature search was performed
      utilizing PubMed. Several recent clinical trials are reviewed in detail, as is
      innovative research evaluating novel agents and surgical techniques which hold
      promise. Expert commentary: The outcome for patients with osteosarcoma has not
      changed in several decades. This plateau in survival rates highlights the need
      for a novel approach towards research. There remains a great deal of interest in
      utilizing the very high risk population of recurrent osteosarcoma patients to
      rapidly and sequentially evaluate novel agents to determine if any of these
      agents hold promise. Several phase II studies are ongoing or in development that
      offer hope based on intriguing preclinical data. Furthermore, initiatives in
      obtaining specimens to further explore the genetic and immunological profile
      behind osteosarcoma will be essential towards identifying novel pathways and
      targets to exploit.

PMID- 29210296
TI  - C-glycosides from the stems of Calophyllum membranaceum.
AB  - Three new C-glycosides, calophymembransides D-F (1-3), were isolated from the
      stems of Calophyllum membranaceum Gardn. et Champ.. The structures were assigned
      on the basis of spectroscopic data. RXRalpha transcriptional inhibition and alpha
      glucosidase inhibition assays indicated that all the isolates were inactive.

PMID- 29210297
TI  - Modern morphological methods for tadpole studies. A comparison of micro-CT, and
      clearing and staining protocols modified for frog larvae.
AB  - Micro-computed tomography (micro-CT) scanning and three-dimensional
      reconstruction have revolutionized morphological studies. Whereas species
      descriptions and comparative studies formerly were based on external appearance
      and dissection, we now can visualize muscles, skeleton and viscera in intact
      animals. In most cases, visualization of internal structures depends on
      appropriate staining methods. Staining with iodine, phosphotungstic acid (PTA)
      and osmium tetroxide are established methods, but some problems remain. Agents
      like osmium tetroxide are toxic and the contrast of cartilage generally is
      unsatisfactory with osmium tetroxide, iodine or PTA. Furthermore, staining
      results vary for different animals and different developmental stages. We
      investigated critical point drying as an inexpensive, nontoxic and rapid
      alternative to staining for frog tadpoles. Critical point drying enables
      visualization of cartilage and its differentiation from muscle tissue. Shrinkage
      generally is acceptable. We also present a protocol for clearing and staining
      frog tadpoles.

PMID- 29210298
TI  - Synthesis and preliminary structure-activity relationship study of 2-aryl-2H
      pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1)
      inhibitors.
AB  - The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell
      cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have
      emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of
      cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a
      congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated
      by in-vitro and in-silico approaches for the first time. A total of 30 PQ
      structures were synthesised in good to excellent yields using conventional or
      microwave heating, highlighting that 14 of them are new chemical entities.
      Noteworthy, in this preliminary study two compounds 4e2 and 4h2 have shown a
      modest but significant reduction in the basal activity of the Chk1 kinase.
      Starting from these preliminary results, we have designed the second generation
      of analogous in this class and further studies are in progress in our
      laboratories.

PMID- 29210300
TI  - FAK inhibitors in Cancer, a patent review.
AB  - INTRODUCTION: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that
      localizes at sites of cell adhesion to the extracellular matrix (ECM) and
      mediates signalling events downstream of integrin engagement of the ECM. FAK is
      known to regulate cell survival, proliferation and migration. Areas covered: FAK
      expression has also been shown to be up-regulated in many cancer types. Previous
      study also indicates that FAK-mediated signaling and functions are intrinsically
      involved in the progression of tumor aggressiveness, suggesting that FAK is a
      promising target for anticancer therapies. Small molecule FAK inhibitors have
      been developed and are being tested in clinical phase trials. Expert Opinion:
      These inhibitors have demonstrated to be effective by inducing tumor cell
      apoptosis in addition to reducing metastasis and angiogenesis. In this review, we
      give updates on the design, synthesis and structure-activity relationship
      analysis of small molecule FAK inhibitors discovered from 2015 until now. We also
      review the FAK inhibitors that are in clinical development and highlight the
      future prospects.

PMID- 29210299
TI  - New cyclopentaquinoline hybrids with multifunctional capacities for the treatment
      of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common progressive form of brain
      neurodegeneration and the most prevailing cause of dementia. Unfortunately, the
      aetiology of AD is not completely studied but different factors are associated
      with the development of AD such as among others low level of acetylcholine,
      aggregation of beta-amyloid (Abeta), hyperphosphorylated tau protein, oxidative
      stress, and inflammation. The study encompass organic syntheses of 2,3-dihydro-1H
      cyclopenta[b]quinoline with 5,6-dichloronicotinic acid and suitable linkers
      derivatives as multifunctional agents for AD treatment. Afterwards self-induced
      amyloid beta aggregation, inhibition studies of acetylcholinesterase and
      butyrylcholinesterase and molecular docking studies were performed. The results
      showed that 3b compound exhibited the best acetylcholinesterase inhibitory
      activity, with IC50 value of 0.052 uM which is lower compared to references.
      Besides, all synthesised compounds showed good butyrylcholinesterase inhibitory
      activity with IC50 values from 0.071 to 0.797 uM. Compound 3b exhibited strong
      Abeta1-42 aggregation inhibitory effect with 25.7% at 5 uM to 92.8% at 100 uM as
      well as good anti-inflammatory effect. Thus, new compounds could create new
      perspectives for further development as a multi-target-directed agent for AD
      treatment.

PMID- 29210301
TI  - Assessment of Cysteine Reactivity of Human Hemoglobin at Its Residue Level: A
      Mass Spectrometry-Based Approach.
AB  - In general, the reactivity of cysteine residues of proteins is measured by 5,5'
      dithiobis(2-nitrobenzoic acid) (DTNB) kinetics using spectrophotometry. Proteins
      with several cysteine residues may exhibit varying DTNB kinetics but residue
      level information can only be obtained with the prior knowledge of their three
      dimensional structure. However, this method is limited in its application to the
      proteins containing chromophores having overlapping absorption profile with 2
      nitro-5-thiobenzoic acid, such as hemoglobin (Hb). Additionally, this method is
      incapable of assigning cysteine reactivity at the residue levels of proteins with
      unknown crystal structures. However, a mass spectrometry (MS)-based platform
      might provide a solution to these problems. In the present study, alkylation
      kinetics of cysteine residues of adult human Hb (Hb A; alpha2beta2) and sickle
      cell Hb (Hb S; HBB: c.20A>T) were investigated using matrix-assisted laser
      desorption/ionization (MALDI) MS. Differential site-specific reactivities of
      cysteine residues of Hb were investigated using alkylation kinetics with
      iodoacetamide (IAM). The observed reactivities corroborated well with the
      differential surface accessibilities of cysteine residues in the crystal
      structures of human Hb. The proposed method might be used to investigate cysteine
      reactivities of all the genetic and post-translational variants of Hb discovered
      to date. In addition, this method can be extended to explore cysteine
      reactivities of proteins, irrespective of the presence of chromophores and
      availability of crystal structures.

PMID- 29210302
TI  - Two new sesquiterpene lactones from leaves of yacon, Smallanthus sonchifolius.
AB  - The chemical constituents of 95% EtOH extract of yacon leaves were separated to
      yield two new sesquiterpene lactones, together with three known compounds. The
      two new compounds were characterized to be 8beta-angeloyloxy-13-methoxyl-11, 13
      dihydromelampolid-14-oic acid methyl ester (1) and 8beta-(3-methylbut-2-enoyl)
      oxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (2) on the
      basis of NMR spectra, HR-MS and other spectroscopic methods. The cytotoxicity of
      compounds 1-5 were evaluated on human hepatoma cell Bel-7402 and all the
      compounds showed moderate cytotoxicity.

PMID- 29210303
TI  - Treatment-focused Ebola trials, supportive care and future of filovirus care.
AB  - INTRODUCTION: During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate
      therapeutics were used in EBOV-infected patients in clinical trials and under
      expanded access for emergency use. This review will focus briefly on medications
      used during the outbreak. We will discuss current therapeutic candidates and
      their status and will then turn to a related and essential topic: supportive care
      and the standard of care for filovirus infected patients. Potential benefits and
      pitfalls of combination therapies for filoviruses will be discussed. Areas
      covered: Clinical trials of therapeutics targeting EBOV; clinical usage of
      therapeutics during recent EBOV outbreak; potential need for combination therapy;
      role of supportive care in treatment of Ebola virus disease (EVD). Expert
      commentary: In the absence of another large scale EBOV outbreak, the path to
      therapeutic product licensure in the United States of America (USA) would need to
      be via the FDA Animal Rule. However, human data may be needed to supplement
      animal data. The future of filovirus therapeutics may therefore benefit by
      establishing the ability to implement clinical trials in an outbreak setting in a
      timely fashion. Supportive care guidelines for filovirus infection should be
      defined and established as standard of care for treatment of EVD.

PMID- 29210304
TI  - Current management of refractory ascites in patients with cirrhosis.
AB  - Liver cirrhosis is a health problem worldwide, and ascites is its principal
      symptom. Refractory ascites is intractable and occurs in 5%-10% of all patients
      with ascites due to cirrhosis. Refractory ascites leads to a poor quality of life
      and high mortality rate. Ascites develops as a result of portal hypertension,
      which leads to water-sodium retention and renal failure. Various therapeutic
      measures can be used for refractory ascites, including large-volume paracentesis,
      transjugular intrahepatic portosystemic shunt, vasoconstrictive drugs, and an
      automated low-flow ascites pump system. However, ascites generally can be
      resolved only by liver transplantation. Because not all patients can undergo
      liver transplantation, traditional approaches are still used to treat refractory
      ascites. The choice of treatment modality for refractory ascites depends, among
      other factors, on the condition of the patient.

PMID- 29210306
TI  - Synergistic antinociceptive activity of combined aqueous extracts of Artemisia
      campestris and Artemisia herba-alba in several acute pain models.
AB  - In this study, total phenolic and flavonoid contents, acute toxicity and the
      antinociceptive activity of Artemisia campestris and Artemisia herba-alba,
      individually and in combination, were investigated using multiple forms of pain
      in animals. Our results have been shown that plants are relatively safe without
      clinical signs of toxicity in animals. Thus, extracts were presented high levels
      in phenolic and flavonoid contents. Artemisia decoctions with 100, 200, 400 mg/kg
      b-w studied dose, clearly attenuate chemical and thermal noxious stimuli in
      writhing, formalin and hot-plate tests, and significantly reduced paw oedema in
      formalin test. Additionally, binary combination forms exhibited a great
      improvement in intensity and amplitude of antinociceptive activity in comparison
      with both plants used individually by a relative interference with opioid system.
      Our findings suggested the central and peripheral analgesic properties and
      confirmed the folkloric medicinal use of these plants in pain symptom treatment.

PMID- 29210305
TI  - Detection of early nocturnal hypoventilation in neuromuscular disorders.
AB  - Objective Nocturnal hypoventilation (NH) is a complication of respiratory
      involvement in neuromuscular disorders (NMD) that can evolve into symptomatic
      daytime hypercapnia if not treated proactively with non-invasive ventilation.
      This study aimed to assess whether NH can be detected in the absence of other
      signs of nocturnal altered gas exchange. Methods We performed nocturnal
      transcutaneous coupled (tc) pCO2/SpO2 monitoring in 46 consecutive cases of
      paediatric-onset NMD with a restrictive respiratory defect (forced vital capacity
      < 60%). Nocturnal hypoventilation was defined as tcPCO2 > 50 mmHg for > 25% of
      recorded time, and hypoxemia as tcSpO2 < 88% for > 5 minutes. Daytime symptoms
      and bicarbonate were recorded after overnight monitoring. Results Twenty-nine of
      46 consecutive patients showed NH. Twenty-three patients did not have nocturnal
      hypoxemia and 18 were clinically asymptomatic. In 20 patients, PaCO2 in daytime
      blood samples was normal. Finally, 13/29 patients with NH had isolated nocturnal
      hypercapnia without nocturnal hypoxia, clinical NH symptoms, or daytime
      hypercapnia. Conclusions Paediatric patients with NMD can develop NH in the
      absence of clinical symptoms or significant nocturnal desaturation. Therefore,
      monitoring of NH should be included among nocturnal respiratory assessments of
      these patients as an additional tool to determine when to commence non-invasive
      ventilation.

PMID- 29210308
TI  - Using multi-criteria decision analysis to appraise orphan drugs: a systematic
      review.
AB  - INTRODUCTION: Multi-criteria decision analysis (MCDA) could potentially solve
      current methodological difficulties in the appraisal of orphan drugs. Areas
      covered: We provide an overview of the existing evidence regarding the use of
      MCDA in the appraisal of orphan drugs worldwide. Three databases (Pubmed, Embase,
      Web of Science) were searched for English, French and German literature published
      between January 2000 and April 2017. Full-text articles were supplemented with
      conference abstracts. A total of seven articles and six abstracts were
      identified. Expert commentary: The literature suggests that MCDA is increasingly
      being used in the context of appraising orphan drugs. It has shown itself to be a
      flexible approach with the potential to assist in decision-making regarding
      reimbursement for orphan drugs. However, further research regarding its
      application must be conducted.

PMID- 29210307
TI  - Amniotic fluid oxidant-antioxidant status in foetal congenital nervous system
      anomalies.
AB  - Objective This study aimed to evaluate the oxidant-antioxidant status of amniotic
      fluid in pregnant women with foetal congenital malformations of the central
      nervous system. Methods We studied pregnant women with foetal congenital nervous
      system anomalies at 16-22 weeks' gestation (n = 36). The control group (n = 30)
      consisted of pregnant women at the same gestational age who underwent
      amniocentesis, resulting in a normal karyotype. We analysed glutathione,
      catalase, and malondialdehyde levels in amniotic fluid. Enzyme activation was
      measured by spectrophotometry. Results The demographic features of the groups
      were similar in terms of age, parity, body mass index, and gestational weeks. We
      detected lower glutathione and catalase levels in the foetal congenital anomaly
      group than in the control group. We detected higher malondialdehyde levels in the
      foetal congenital anomaly group than in the control group. Conclusion In the
      organism, the rate of formation of free radicals and their rate of removal are
      balanced, and this is called oxidative balance. As long as oxidative stability is
      achieved, the organism is not affected by free radicals. This fact should be kept
      in mind to avoid any type of teratogenic agent that could lead to congenital
      disorders.

PMID- 29210309
TI  - Identification and characterization of a locus putatively involved in colanic
      acid biosynthesis in Vibrio alginolyticus ZJ-51.
AB  - Colanic acid (CA) is a group I extracellular polysaccharide (EPS) that
      contributes to resistance against adverse environments in many members of the
      Enterobacteriaceae. In the present study, a genetic locus EPSC putatively
      involved in CA biosynthesis was identified in Vibrio alginolyticus ZJ-51, which
      undergoes colony morphology variation between translucent/smooth (ZJ-T) and
      opaque/rugose (ZJ-O). EPSC in ZJ-T carries 21 ORFs and resembles the CA cluster
      of Escherichia coli K-12. The deletion of EPSC led to decreased EPS and biofilm
      formation in both genetic backgrounds but no alternation of lipopolysaccharide.
      The loss of this locus also changed the colony morphology of ZJ-O on the 2216E
      plate and reduced the motility of ZJ-T. Compared with ZJ-T, ZJ-O lacks a 10-kb
      fragment (epsT) in EPSC containing homologs of wecA, wzx and wzy that are
      essential for O-antigen synthesis. However, the deletion or overexpression of
      epsT resulted in no change of colony morphology, biofilm formation or EPS
      production. This study reported at the first time a genetic locus EPSC that may
      be involved in colanic acid synthesis in V. alginolyticus ZJ-51, and found that
      it was related to EPS biosynthesis, biofilm formation, colony morphology and
      motility, which may shed light on the environmental adaptation of the vibrios.

PMID- 29210310
TI  - Outcome of pinning in patients with slipped capital femoral epiphysis: risk
      factors associated with avascular necrosis, chondrolysis, and femoral
      impingement.
AB  - Objective This study aimed to assess the principal risk factors that could lead
      to the most common long-term complications of slipped capital femoral epiphysis,
      such as avascular necrosis, chondrolysis, and hip impingement. Methods We
      conducted a single-centre, retrospective study and evaluated patients (70
      patients, 81 hips) who were treated for slipped capital femoral epiphysis from
      2010 to 2015 and who underwent pinning. We measured the severity of displacement
      radiologically using the Southwick angle. Postoperative radiographs were
      evaluated for the most frequent long-term complications of avascular necrosis
      (AVN), chondrolysis, and femoral acetabular impingement (FAI). Results We found
      seven cases of AVN, 14 cases of chondrolysis, and 31 hips had an alpha angle of
      60 degrees . Sex, ambulation, and symptoms did not affect development of these
      complications. Patients with a normal weight were almost two times more likely to
      develop FAI. Patients with moderate and severe slips had a similar percentage of
      AVN. In severe slips, 85.7% of patients had an alpha angle higher than 60 degrees
      . Conclusions This study shows that severe slips have a higher risk of developing
      AVN and hip impingement. Every patient who suffers from SCFE (even the mildest
      forms) should be regularly checked for FAI.

PMID- 29210311
TI  - The role of gut microbiota in the modulation of drug action: a focus on some
      clinically significant issues.
AB  - INTRODUCTION: A healthy gut microbiota is necessary for the normal operation of
      several body functions, including gastrointestinal sensitivity and motility,
      lipid and glucid metabolism, immune surveillance, and host behavior. In addition,
      intestinal bacteria contribute to determining the pharmacological properties of
      several drugs by producing different drug metabolizing enzymes. Areas covered:
      Four enzymatic processes are discussed: prodrug activation; drug inactivation;
      drug deconjugation; and hydrolysis of natural glycosides with further metabolism
      of released aglycones. For each of these processes, a literature search has been
      undertaken on certain paradigmatic examples that have significant clinical
      implications: aminosalicylates and anthranoid laxatives; digoxin; irinotecan and
      non-steroidal anti-inflammatory drugs (NSAIDs); rutin, diosmin, and baicalin.
      Expert commentary: The modulation of certain reactions catalyzed by gut bacterial
      enzymes may offer new opportunities to improve the clinical efficacy of drugs
      such as aminosalicylates, and natural glycosides by increasing their metabolic
      transformation, and of digoxin by reducing its inactivation, or to decrease the
      lower intestinal toxicity of irinotecan, and NSAIDs by inhibiting the hydrolytic
      cleavage of their conjugates. Randomized clinical trials are awaited to clarify
      whether new intervention strategies may modulate these processes and provide
      clinical benefits such as improved therapeutic outcomes and drug safety profiles.

PMID- 29210312
TI  - Development and optimization of a novel drug free nanolipid vesicular system for
      treatment of osteoarthritis.
AB  - OBJECTIVE: The goal of this study is to improve the transdermal delivery of
      phosphatidylcholine (PC) via constructing a novel nanolipid vesicular system
      (NLVS) with high level of permeability through the stratum corneum (SC).
      SIGNIFICANCE: In our study, a novel drug free NLVS was developed. The system
      depends on PC boundary cartilage lubrication to relieve osteoarthritic pain
      without developing gastrointestinal problems associated with anti-inflammatory
      drug. MATERIALS AND METHODS: A full two-level (23) factorial design is applied to
      optimize the quality of the prepared NLVS. The selected independent variables are
      the concentration of PC, the concentration of edge activator (EA), and EA type.
      The developed NLVS was evaluated for in-vitro, ex-vivo as well as in-vivo
      efficacy in rat animal model. RESULTS: Based on the factorial design, the
      selected formulation variables significantly affect the tested responses. The
      prepared NLV formulations have a particle size (PS)in the range of 10.34 to 496.3
      nm, polydispersity index (PdI) values less than one, and negative zeta potential
      (ZP) range of -1.42 to -32.01 mV. In-vitro and ex-vivo study results reveal that
      the designed NLVS is effective in sustaining PC release and enhancing its
      transdermal permeation over 24 h. The optimal permeation flux through ex-vivo
      study is 0.415 mg/cm2/h following zero-order kinetics. Moreover, in-vivo study of
      the optimized formulations demonstrated remarkable reduction in inflammatory
      mediators associated with osteoarthritis (OA). CONCLUSION: The results indicate
      that the optimized drug free NLVS significantly augment transdermal delivery of
      PC and have a potential role in treatment of OA without the risk of systemic side
      effects.

PMID- 29210313
TI  - RETRACTED: Pain predicts poorer health-related quality of life in childhood-onset
      systemic lupus erythematosus: a cohort study.

PMID- 29210314
TI  - Evaluation of sulfamethazine removal kinetics using fixed structured bed
      bioreactor.
AB  - The use of anaerobic biomass attached to a support has been recently presented as
      a good prospect in the treatment of wastewater containing recalcitrant compounds,
      such as sulfamethazine (SMZ). SMZ has been found in swine wastewater and sewage
      treatment plants, which motivates assessing their degradation by new wastewater
      treatment technologies. Thus, this paper describes the use of a continuous fixed
      structured bed bioreactor for the purpose of evaluating SMZ removal kinetics
      present in lab-made wastewater. The analysis of SMZ used online solid-phase
      extraction coupled to liquid chromatography/tandem mass spectrometry (SPE online
      LC-MS/MS). Chemical oxygen demand (COD) was also monitored to evaluate the
      organic matter removal. The bioreactor was operated under mesophilic conditions
      (30[Formula: see text]C), with a hydraulic retention time of 24 h. In order to
      evaluate SMZ removal, four different concentration levels were studied: 200, 400,
      600, and 800 ng L-1. COD removal efficiency obtained for filtered effluent kept
      at 91.01% and there was no interference due to the increase of SMZ concentration.
      For SMZ, the removal efficiencies were of [Formula: see text] for 200 ng L-1
      concentration level; [Formula: see text] for 400 ng L-1; [Formula: see text] for
      600 ng L-1, and [Formula: see text] for 800 ng L-1. COD removal kinetics
      presented a first-order apparent removal rate constant ([Formula: see text]) of
      [Formula: see text] h-1. SMZ also showed a first-order apparent removal rate
      constant of [Formula: see text] h-1 for the following concentrations levels: 200,
      400, 600, and 800 ng L-1.

PMID- 29210315
TI  - Expression of lamina proteins Lamin and Kugelkern suppresses stem cell
      proliferation.
AB  - The nuclear lamina is involved in numerous cellular functions, such as gene
      expression, nuclear organization, nuclear stability, and cell proliferation. The
      mechanism underlying the involvement of lamina is often not clear, especially in
      physiological or developmental contexts. Here we investigate the role and
      activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in
      proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies.
      We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of
      Lam or Kuk strongly suppressed proliferation. The anti-proliferative activity is,
      at least in part, due to suppression of Jak/Stat but not Delta/Notch signaling.
      Lam expression suppresses Jak/Stat signaling by normalization of about 50% of the
      Stat target genes in ISCs.

PMID- 29210316
TI  - Long-living RNA in the CNS of terrestrial snail.
AB  - Click-iT method can be used to trace the neurons where the newly synthesized RNA
      transcripts occur. Our experiments performed with the CNS of terrestrial mollusk
      Helix demonstrate that 5-ethynyluridine (EU) is selectively incorporated in RNA
      but not in DNA. The time of EU accumulation necessary for its detection was about
      several hours. EU was injected into the body cavity of adult mollusks, and was
      detectable in neurons for several days. In juveniles, EU was introduced via
      bathing of snails in the EU-containing saline, and was reliably detected within
      time period of several weeks. Our data suggest that short-living forms of RNA
      cannot be detected by Click-iT method, while the long-living forms of RNA can be
      spatially detected in individual neurons.

PMID- 29210317
TI  - Enhanced ocular bioavailability of fluconazole from niosomal gels and
      microemulsions: formulation, optimization, and in vitro-in vivo evaluation.
AB  - Fungal keratitis may cause vision loss if it is not treated. Methods other than
      ocular delivery exhibited several limitations. No previous studies investigated
      and compared ocular bioavailability of fluconazole (FLZ) from niosomal gels and
      microemulsions. Niosomal gels of FLZ (0.3% w/w) based on Span(r) 60 and
      cholesterol (CH) using 1% w/w carbopol(r) 934 (CP) were evaluated. FLZ
      microemulsions (0.3% w/v) containing isopropyl myristate (IPM, as oil phase) and
      a 3:1 mixture of Tween(r) 80 (as surfactant) and polyethylene glycol 400 (PEG
      400, as cosurfactant) were characterized. Optimized formulations were compared
      for their ocular bioavailability in rabbit's. Nanoscopic niosomes (63.67-117.13
      nm) and microemulsions (57.05-59.93 nm) showed respective negative zeta potential
      ranges of -45.37 to -61.40 and -20.50 to -31.90 mV and sustained release up to 12
      h. Entrapment efficiency (EE%) of niosomes ranged from 56.48% to 70.67%. Niosomal
      gels were more sustainable than niosomes and microemulsions. The most stable
      niosomal gel based on Span(r) 60 and CH at a molar ratio of 5:5 and microemulsion
      containing 45% w/w IPM and 40% w/w of 3:1 Tween(r) 80-PEG 400 mixture
      significantly (p < 0.0001) enhanced FLZ ocular bioavailability compared with its
      solution. Niosomal gel showed higher bioavailability than microemulsion by ~2
      fold.

PMID- 29210318
TI  - Inhalation device options for the management of chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic
      respiratory symptoms and airflow limitation, resulting from abnormalities in the
      airway and/or damage to the alveoli. Primary care physicians manage the
      healthcare of a large proportion of patients with COPD. In addition to
      determining the most appropriate medication regimen, which usually includes
      inhaled bronchodilators with or without inhaled corticosteroids, physicians are
      charged with optimizing inhalation device selection to facilitate effective drug
      delivery and patient adherence. The large variety of inhalation devices currently
      available present numerous challenges for physicians that include: (1) gaining
      knowledge of and proficiency with operating different device classes; (2)
      identifying the most appropriate inhalation device for the patient; and (3)
      providing the necessary education and training for patients on device use. This
      review provides an overview of the inhalation device types currently available in
      the United States for delivery of COPD medications, including information on
      their successful operation and respective advantages and disadvantages, factors
      to consider in matching a device to an individual patient, the need for device
      training for patients and physicians, and guidance for improving treatment
      adherence. Finally, the review will discuss established and novel tools and
      technology that may aid physicians in improving education and promoting better
      adherence to therapy.

PMID- 29210319
TI  - Carcinogenicity of ethylene oxide: key findings and scientific issues.
AB  - In support of the Integrated Risk Information System (IRIS), the U.S.
      Environmental Protection Agency (EPA) completed an evaluation of the inhalation
      carcinogenicity of ethylene oxide (EtO) in December 2016. This article reviews
      key findings and scientific issues regarding the carcinogenicity of EtO in EPA's
      Carcinogenicity Assessment. EPA's assessment critically reviewed and
      characterized epidemiologic, laboratory animal, and mechanistic studies
      pertaining to the human carcinogenicity of EtO, and addressed some key scientific
      issues such as the analysis of mechanistic data as part of the cancer hazard
      evaluation and to inform the quantitative risk assessment. The weight of evidence
      from the epidemiologic, laboratory animal, and mechanistic studies supports a
      conclusion that EtO is carcinogenic in humans, with the strongest human evidence
      linking EtO exposure to lymphoid and breast cancers. Analyses of the mechanistic
      data establish a key role for genotoxicity and mutagenicity in EtO-induced
      carcinogenicity and reveal little evidence supporting other mode-of-action
      hypotheses. In conclusion, EtO was found to be carcinogenic to humans by
      inhalation, posing a potential human health hazard for lymphoid and breast
      cancers.

PMID- 29210320
TI  - Genetic variation in statin intolerance and a possible protective role for
      UGT1A1.
AB  - The etiology of statin intolerance is hypothesized to be due to genetic variants
      that impact statin disposition and clearance. We sought to determine whether
      genetic variants were associated to statin intolerance. The studied cohort
      consisted of hyperlipidemic participants (n = 90) clinically diagnosed with
      statin intolerance by a cardiologist and matched controls without statin
      intolerance. Creatine kinase activity, lipid profiles and genetic analyses were
      performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3
      sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1
      c.3435C>T, ABCG2 c.421C>A and GATM rs9806699. Although lipids were higher in
      cases, genetic variant minor allele frequencies were similar between cases and
      controls, except for UGT1A1*28, which was less prevalent in cases than controls.

PMID- 29210321
TI  - Lessons for reviewing clinical trials using induced pluripotent stem cells:
      examining the case of a first-in-human trial for age-related macular
      degeneration.

PMID- 29210322
TI  - Plasma-induced synthesis of chitosan-g-polyacrylamide and its flocculation
      performance for algae removal.
AB  - Chitosan (CS)-g-polyacrylamide (PAM) is a highly efficient and environmentally
      friendly flocculant, which was synthesized through plasma-induced graft
      copolymerization of CS and acrylamide (AM). The effects of monomer concentration,
      AM:CS ratio, discharge power, discharge time, post-polymerization temperature,
      and post-polymerization time on the intrinsic viscosity, grafting ratio, and
      grafting efficiency of CS-g-PAM were investigated. The optimum conditions of
      graft copolymerization were as follows: 20% monomer concentration, 7:3 AM:CS
      ratio, 40 W discharge power, 90 s discharge time, 50 degrees C post
      polymerization temperature, and 24 h post-polymerization time. The structural
      characteristics of CS-g-PAM were characterized by Fourier-transform infrared
      spectroscopy, scanning electron microscopy, and X-ray diffraction. CS-g-PAM
      exhibited better flocculation efficiency than the commercially available PAM in
      both diatomite-simulated wastewater and low-turbidity algal water. The optimal
      turbidity removal efficiency for the diatomite-simulated wastewater was 99.9%,
      which was obtained with 6 mg L-1 of CS-g-PAM at pH 11.0 and 250 s-1 of velocity
      gradient. In low-turbidity algal water, the optimal removal efficiencies for
      chlorophyll-a, turbidity, and COD were 93.6%, 94.5%, and 98.2%, respectively.

PMID- 29210323
TI  - Effect of genetic variation in UGT1A and ABCB1 on moxifloxacin pharmacokinetics
      in South African patients with tuberculosis.
AB  - AIM: We assessed the effect of genetic variability in UGT1A and ABCB1 genes on
      moxifloxacin pharmacokinetics. METHODS: Genotypes for selected UGT1A and ABCB1
      SNPs were determined using a TaqMan(r) Genotyping OpenArrayTM and high-resolution
      melt analysis for rs8175347. A nonlinear mixed-effects model was used to describe
      moxifloxacin pharmacokinetics. RESULTS: Genotypes of UGT1A SNPs, rs8175347 and
      rs3755319 (20.6% lower and 11.6% increased clearance, respectively) and ABCB1 SNP
      rs2032582 (40% reduced bioavailability in one individual) were significantly
      associated with changes in moxifloxacin pharmacokinetic parameters. CONCLUSION:
      Genetic variation in UGT1A as represented by rs8175347 to a lesser extent
      rs3755319 and the ABCB1 rs2032582 SNP is modestly associated with the
      interindividual variability reported in moxifloxacin pharmacokinetics and
      exposure. Clinical relevance of the effects of genetic variation on moxifloxacin
      pharmacokinetic requires further investigation.

PMID- 29210324
TI  - Patterns of locomotor regulation during the pole vault approach phase.
AB  - A successful approach phase is key to achieving high performances in the pole
      vault. The aim of this study was to explore the nature of locomotor control
      patterns during the pole vault approach phase. Fourteen well-trained athletes
      performed ten jumps which were recorded using 2D video sampling at 200 Hz and
      analysed. Key kinematics were reconstructed from camera data using a modified 2D
      DLT. Patterns of regulation were determined from the standard deviation of
      footfall locations during the approach phase. These patterns were found to be
      highly individual but structural differences between those who did and those who
      did not regulate were identified. Regulation of locomotion was associated with an
      ability to produce functionally adaptable movement patterns and the consistent
      achievement of desired performance outcomes. Coaches should include training
      exercises that require intentional use of regulation to aid athletes in achieving
      the flexibility to adapt to changing constraints during the approach phase.
      Athletes should be considered on an individual basis in order to effectively,
      efficiently and safely improve performance.

PMID- 29210326
TI  - Comparative evaluation of heart rate-based monitors: Apple Watch vs Fitbit Charge
      HR.
AB  - The purpose of this investigation was to examine the validity of energy
      expenditure (EE), steps, and heart rate measured with the Apple Watch 1 and
      Fitbit Charge HR. Thirty-nine healthy adults wore the two monitors while
      completing a semi-structured activity protocol consisting of 20 minutes of
      sedentary activity, 25 minutes of aerobic exercise, and 25 minutes of light
      intensity physical activity. Criterion measures were obtained from an Oxycon
      Mobile for EE, a pedometer for steps, and a Polar heart rate strap worn on the
      chest for heart rate. For estimating whole-trial EE, the mean absolute percent
      error (MAPE) from Fitbit Charge HR (32.9%) was more than twice that of Apple
      Watch 1 (15.2%). This trend was consistent for the individual conditions. Both
      monitors accurately assessed steps during aerobic activity (MAPEApple: 6.2%;
      MAPEFitbit: 9.4%) but overestimated steps in light physical activity. For heart
      rate, Fitbit Charge HR produced its smallest MAPE in sedentary behaviors (7.2%),
      followed by aerobic exercise (8.4%), and light activity (10.1%). The Apple Watch
      1 had stronger validity than the Fitbit Charge HR for assessing overall EE and
      steps during aerobic exercise. The Fitbit Charge HR provided heart rate estimates
      that were statistically equivalent to Polar monitor.

PMID- 29210327
TI  - 5-HTTLPR polymorphism is associated with nostalgia proneness: The role of
      neuroticism.
AB  - Nostalgia, a sentimental longing for the past, is a self-relevant and social
      emotion. Nostalgia proneness is associated with alleviation of distress or
      instability (e.g., neuroticism). Although nostalgia proneness is heritable, the
      specific molecular contributors to this heritability are unknown. We focused on a
      polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) as a
      possible biological basis of nostalgia proneness, because the serotonin system
      has been associated with sensitivity to negative experience. Participants (N =
      397 adults) who had reported levels of nostalgia proneness were genotyped. A
      subsample also completed a measure of neuroticism. Participants with the 5-HTTLPR
      short allele were higher on nostalgia proneness than those without this allele.
      Neuroticism mediated the relation between 5-HTTLPR and nostalgia proneness. These
      findings enrich our understanding of the genetic and personality underpinnings of
      nostalgia.

PMID- 29210325
TI  - Foods, Dietary Patterns and Occupational Class and Leukocyte Telomere Length in
      the Male Population.
AB  - Telomeres contain TTAGGG repetitive sequences and are located at the end of human
      chromosomes. Telomere dysfunction is associated with some age-related and chronic
      diseases, but its relationship with foods, dietary patterns, and occupational
      class in the young male population is not yet known. In this cross-sectional
      study, 300 healthy men, residents of Tehran, aged 25-40 years were enrolled from
      January to December 2016. We employed a cross-sectional study of 300 healthy
      people, residents of Tehran, aged 25-40 years. A food frequency questionnaire was
      used to obtain food intakes of all participants and converted into actual food
      intake (g/day). The principal components analysis was used to determine dietary
      patterns and other demographic characteristics. Leukocyte telomere length (TL)
      was measured by quantitative real-time polymerase chain reaction (PCR) to measure
      number of telomere repeat copy number (T) to the relative number of 36B4 copies
      (S) (T/S ratio). T/S in office-workers, waste recyclers, and other workers were
      1.22 +/- 0.4, 1.08 +/- 0.3, and 1.094 +/- 0.34, respectively. The results of
      multivariate linear regression adjusted for age, body mass index (BMI), and
      smoking were showed that whole grains (beta = 0.02; p = .05), refined grains,
      fruits and vegetables, fish and dairy products were associated with an increase
      in log-T/S, but consumption of nuts and seeds (beta = -0.00072; p = .06), meats
      (beta = -0.00043; p = .9), produced meats (beta = -0.00238; p = .03), oils and
      solid fats (beta = -0.00146; p = .03) had a negative relationship with log-T/S in
      all studied occupational classes. A positive relationship was reported between
      the healthy (beta = 0.017; p = .2) and traditional dietary pattern (beta = 0.012;
      p = .4) with log-T/S, but western pattern identified negative relationship (beta
      = -0.004; p = .7). Adherence to a healthy (with consumption whole grains, refined
      grains, dairy, and cereals) and then traditional pattern with increased
      consumption of fruits, vegetables and whole grains, fish and dairy products are
      necessary to prevent TL destruction in all studied occupational classes.

PMID- 29210328
TI  - DNA variants in DHFR gene and response to treatment in children with childhood B
      ALL: revisited in AIEOP-BFM protocol.
AB  - AIM: We have previously reported an association of dihydrofolate reductase
      promoter polymorphisms with reduced event-free survival in childhood acute
      lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute
      protocol. Here, we assessed whether these associations are applicable to other
      protocol, based on different methotrexate doses. METHODS: Genotypes for six tag
      polymorphisms and resulting haplotypes were analyzed for an association with ALL
      outcome. RESULTS: The association was found with the polymorphisms A-680C, A-317G
      and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably
      higher risk of events compared with noncarriers and a lower probability of event
      free survival (21.4 vs 81.3%). CONCLUSION: The role of DHFR variants in
      predicting the outcome of childhood ALL extends beyond single-treatment protocol
      and can be useful biomarker in personalizing treatment.

PMID- 29210329
TI  - A concise evidence-based physical examination for diagnosis of acromioclavicular
      joint pathology: a systematic review.
AB  - OBJECTIVES: The clinical examination of the shoulder joint is an undervalued
      diagnostic tool for evaluating acromioclavicular (AC) joint pathology. Applying
      evidence-based clinical tests enables providers to make an accurate diagnosis and
      minimize costly imaging procedures and potential delays in care. The purpose of
      this study was to create a decision tree analysis enabling simple and accurate
      diagnosis of AC joint pathology. METHODS: A systematic review of the Medline,
      Ovid and Cochrane Review databases was performed to identify level one and two
      diagnostic studies evaluating clinical tests for AC joint pathology. Individual
      test characteristics were combined in series and in parallel to improve
      sensitivities and specificities. A secondary analysis utilized subjective pre
      test probabilities to create a clinical decision tree algorithm with post-test
      probabilities. RESULTS: The optimal special test combination to screen and
      confirm AC joint pathology combined Paxinos sign and O'Brien's Test, with a
      specificity of 95.8% when performed in series; whereas, Paxinos sign and Hawkins
      Kennedy Test demonstrated a sensitivity of 93.7% when performed in parallel.
      Paxinos sign and O'Brien's Test demonstrated the greatest positive likelihood
      ratio (2.71); whereas, Paxinos sign and Hawkins-Kennedy Test reported the lowest
      negative likelihood ratio (0.35). CONCLUSION: No combination of special tests
      performed in series or in parallel creates more than a small impact on post-test
      probabilities to screen or confirm AC joint pathology. Paxinos sign and O'Brien's
      Test is the only special test combination that has a small and sometimes
      important impact when used both in series and in parallel. Physical examination
      testing is not beneficial for diagnosis of AC joint pathology when pretest
      probability is unequivocal. In these instances, it is of benefit to proceed with
      procedural tests to evaluate AC joint pathology. Ultrasound-guided corticosteroid
      injections are diagnostic and therapeutic. An ultrasound-guided AC joint
      corticosteroid injection may be an appropriate new standard for treatment and
      surgical decision-making. LEVEL OF EVIDENCE: II - Systematic Review.

PMID- 29210330
TI  - Subcutaneous local anesthetic infusion could eliminate use of epidural analgesia
      after the Nuss procedure.
AB  - AIM: To compare outcomes of continuous subcutaneous infusion of local anesthetic
      and epidural analgesia following the Nuss procedure. PATIENTS & METHODS: A
      retrospective chart review compared patients managed with subcutaneous local
      anesthetic infusion (n = 12) versus thoracic epidural (n = 19) following the Nuss
      procedure from March 2013 to June 2015. RESULTS: There was no difference in
      hospital length of stay or days on intravenous narcotics. Epidural catheter
      placement prolonged operating room time (146.58 +/- 28.30 vs 121.42 +/- 21.98
      min, p = 0.01). Average pain scores were slightly higher in the subcutaneous
      infusion group (3.72 +/- 1.62 vs 2.35 +/- 0.95, p = 0.02), but of negligible
      clinical significance. CONCLUSION: Continuous subcutaneous infusion of local
      anesthetic could eliminate the need for thoracic epidural for pain management
      after the Nuss procedure.

PMID- 29210331
TI  - Phytocapping: an alternate cover option for municipal solid waste landfills.
AB  - Landfill gases are produced due to biodegradation of organic fraction of
      municipal solid waste (MSW) when water comes into contact with buried wastes
      under prevailing anaerobic conditions. To minimize the percolation of water in
      landfills, the conventional approaches such as clay capping is still practised in
      India. As landfill gas extraction system is an expensive technique,'Phytocapping'
      to mitigate landfill gases and to minimize percolation of water into the landfill
      can be one of the attractive alternatives. The present study aimed to determine
      efficiency of a laboratory-scale phytocap in terms of methane emissions, heavy
      metals' remediation and plant-soil interactions in Indian climatic conditions
      using six native plants in five planters (30 cm * 30 cm * 25 cm) with 5 kg of
      MSW. Overall methane oxidation due to vegetation was observed throughout the
      vegetated planters when compared to non-vegetated planters. Root zone methane
      concentrations were also monitored for the plant species, with the highest
      reduction occurring in root zones of Agave sisalana and Bambusa sulfurea and
      highest trace elements' remediation potential was observed in Brassica juncea and
      Helianthus annus plants. 96-98% of CH4 oxidation and 85-89% of heavy metals
      remediation was achieved through the study.

PMID- 29210332
TI  - Dopamine gene variants in opioid addiction: comparison of dependent patients,
      nondependent users and healthy controls.
AB  - AIM: To determine whether specific dopaminergic system gene variants are
      associated with opioid dependence. PATIENTS & METHODS: Subjects included 153
      healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent.
      Genotypes of 90 variants in 13 genes were examined. RESULTS: The most significant
      results were obtained for DA beta-hydroxylase variants, rs2073837 and rs1611131,
      which were associated with protection from addiction (q = 0.0172, 0.0415,
      respectively) and the functional TH variant, rs2070762, was associated with more
      risk (q = 0.0387). The three variants also showed a combined effect that remained
      significant after correction for multiple testing (pfinal = 0.0039). CONCLUSION:
      These data offer support that dopaminergic gene variants have a role in opioid
      dependence and warrant further study.

PMID- 29210333
TI  - Training reproductive health professionals in a post-conflict environment:
      exploring medical, nursing, and midwifery education in Mogadishu, Somalia.
AB  - Following two decades of civil war, Somalia recently entered the post-conflict
      rebuilding phase that has resulted in the rapid proliferation of higher education
      institutions. Given the high maternal mortality ratio, the federal government has
      identified the reproductive health education of health service professionals as a
      priority. Yet little is known about the coverage of contraception, abortion,
      pregnancy, childbirth, and sexual and gender-based violence (SGBV) in medicine,
      nursing, or midwifery. In 2016, we conducted a multi-methods study to understand
      the reproductive health education and training landscape and identify avenues by
      which development of the next generation of health service professionals could be
      improved. Our study comprised two components: interviews with 20 key informants
      and 7 focus group discussions (FGDs) with 48 physicians, nurses, midwives, and
      medical students. Using the transcripts, memos, and field notes, we employed a
      multi-phased approach to analyse our data for content and themes. Our findings
      show that reproductive health education for medical and nursing students is
      inconsistent and significant content gaps, particularly in abortion and SGBV,
      exist. Students have few clinical training opportunities and the overarching
      challenges plaguing higher education in Somalia also impact health professions
      programmes in Mogadishu. There is currently a window of opportunity to develop
      creative strategies to improve the breadth and depth of evidence-based education
      and training, and multi-stakeholder engagement and the promotion of South-South
      exchanges appear warranted.

PMID- 29210334
TI  - False beliefs predict increased circumcision satisfaction in a sample of US
      American men.
AB  - Critics of non-therapeutic male and female childhood genital cutting claim that
      such cutting is harmful. It is therefore puzzling that 'circumcised' women and
      men do not typically regard themselves as having been harmed by the cutting,
      notwithstanding the loss of sensitive, prima facie valuable tissue. For female
      genital cutting (FGC), a commonly proposed solution to this puzzle is that women
      who had part(s) of their vulvae removed before sexual debut 'do not know what
      they are missing' and may 'justify' their genitally-altered state by adopting
      false beliefs about the benefits of FGC, while simultaneously stigmatising
      unmodified genitalia as unattractive or unclean. Might a similar phenomenon apply
      to neonatally circumcised men? In this survey of 999 US American men, greater
      endorsement of false beliefs concerning circumcision and penile anatomy predicted
      greater satisfaction with being circumcised, while among genitally intact men,
      the opposite trend occurred: greater endorsement of false beliefs predicted less
      satisfaction with being genitally intact. These findings provide tentative
      support for the hypothesis that the lack-of-harm reported by many circumcised
      men, like the lack-of-harm reported by their female counterparts in societies
      that practice FGC, may be related to holding inaccurate beliefs concerning
      unaltered genitalia and the consequences of childhood genital modification.

PMID- 29210336
TI  - Simplification to dual-therapy containing lamivudine and darunavir/ritonavir or
      atazanavir/ritonavir in HIV-infected patients on virologically suppressive
      antiretroviral therapy.
AB  - BACKGROUND: The ritonavir-boosted protease inhibitor (PI/r)-based dual regimens
      are warranted in order to optimize the combination antiretroviral therapy (cART),
      prevent the long-term toxicity and reduce the cost of treatments. METHODS: We
      performed an observational, retrospective study of HIV-infected patients on
      suppressive antiretroviral therapy who switched to a dual regimen containing
      lamivudine (3TC) plus darunavir/ritonavir (DRV/r) 800/100 mg qd or
      atazanavir/ritonavir (ATV/r) 300/100 mg qd. RESULTS: As a whole, 122 well-treated
      patients (mean age, 45.2 years; mean CD4 T + lymphocyte count, 589 cells/mm3;
      mean duration of current cART, 3.1 years) were enrolled. Current antiretroviral
      regimen included tenofovir/emtricitabine in 91 subjects, abacavir/lamivudine in
      25, lopinavir/r in 41, DRV/r in 38 and ATV/r in 33. Baseline mean estimated
      glomerular filtration rate (eGFR) was 94.2 mL/min/1.73 m2, and proteinuria was
      detected in 46 subjects (38%). Overall 70 subjects switched to 3TC + DRV/r (group
      A) and 52 to 3TC + ATV/r (group B). After 12 months, 65 patients (92.8%) in group
      A and 46 (88.4%) in group B showed HIV RNA <20 copies/mL. A significant and
      comparable increase in eGFR was observed in group A and B (+3.8 and +3.1
      mL/min/1.73 m2, respectively), such as a significant decrease in prevalence of
      proteinuria. A significantly greater increase in total bilirubin concentration
      was reported in group B than in group A. CONCLUSION: In our study, simplification
      to a dual therapy containing 3TC + DRV/r or ATV/r in virologically suppressed
      patients was effective and showed a good tolerability profile.

PMID- 29210338
TI  - What would the patient have wanted?

PMID- 29210337
TI  - Death following ceftazidime-induced Kounis syndrome.
AB  - Kounis syndrome, also known as allergic myocardial infarction or allergic angina
      syndrome, coincides with chest pain and allergic reactions. It involves the
      activation of interrelated inflammatory cells following allergic, anaphylactic or
      anaphylactoid insults. We report a case of Kounis syndrome complicated by an
      injection of ceftazidime. A 52-year-old man developed shortness of breath and
      hypotension, leading to immediate unconsciousness, after a ceftazidime injection.
      Despite intensive care management, he showed no improvement and died
      approximately 19 h after ceftazidime administration. Autopsy showed massive
      laryngeal oedema, mucous plugging and collapsed lungs. An ImmunoCAP tryptase
      assay showed the tryptase level in an autopsy sample to be 118 ug/L (normal <
      11.4 ug/L). Microscopy of the myocardium showed cellular infiltration preceding
      myocardial necrosis. These findings support the pathophysiological theory of
      Kounis syndrome, with cellular infiltration proposed as the cause of myocardial
      injury rather than an effect related to the healing process.

PMID- 29210335
TI  - Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian
      inflammatory bowel disease patients.
AB  - BACKGROUND: Genetic variants of TPMT and NUDT15 have been reported to predict the
      inter-patient variability in response and toxicity profiles of patients receiving
      thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding
      thiopurine doses has been questionable, in part due to underlying differences in
      the prevalence of TPMT variants in both Caucasian and Asian populations. Several
      NUDT15 variants have been associated with thiopurine-induced leukopenia,
      particularly in Asian cohorts. So far, none have been reported in a multiethnic
      Asian population. AIM: To investigate the associations between TPMT and NUDT15
      variants with thiopurine-induced myelotoxicity in 129 Asian inflammatory bowel
      disease patients. MATERIALS & METHODS: Pyrosequencing was performed to screen for
      TPMT and NUDT15 variants. Intracellular steady-state metabolite concentrations
      were quantified using liquid chromatography-tandem mass spectrometry. RESULTS:
      Significant declines in nadir white blood cell, absolute neutrophil count and
      platelet counts were observed with increasing copy numbers of the risk T allele
      at NUDT15 c.415C>T locus (overall p < 0.05) within 4, 8 and 12 weeks and 6 months
      after thiopurine initiation. Patients with low and intermediate NUDT15 activity,
      as inferred from haplotype pairs, had significantly higher risks of leukopenia (p
      = 0.000253) and neutropenia (p = 0.002) compared with patients with normal NUDT15
      activity. CONCLUSION: These findings highlight the critical relevance of NUDT15
      pharmacogenetics in predicting for thiopurine-induced myelotoxicity and confirm
      the lack of significance of TPMT variants in Asian inflammatory bowel disease
      patients.

PMID- 29210339
TI  - Gender identity, dysphoria and change.

PMID- 29210340
TI  - Homicidal methanol poisoning in filicide-suicide.
AB  - Most methanol poisonings are accidental. We present a rare case of filicide
      suicide, where a youth was killed by methanol poisoning and his parents then
      committed suicide by jumping in front of a running train. The father's suicide
      note explains the crime.

PMID- 29210341
TI  - "Without this program, women can lose their lives": migrant women's experiences
      with the Safe Abortion Referral Programme in Chiang Mai, Thailand.
AB  - For displaced and migrant women in northern Thailand, access to health care is
      often limited, unwanted pregnancy is common, and unsafe abortion is a major
      contributor to maternal death and disability. Based on a pilot project and
      situational analysis research, in 2015 a multinational team introduced the Safe
      Abortion Referral Programme (SARP) in Chiang Mai, Thailand, to reduce the socio
      linguistic, economic, documentation, and transportation barriers women from Burma
      face in accessing safe and legal abortion care in Thailand. Our qualitative study
      documented the experiences of women with unwanted pregnancies who accessed the
      SARP in order to inform programme improvement and expansion. We conducted 22 in
      depth, in-person interviews and analysed them for content and themes using
      deductive and inductive techniques. Women were overwhelmingly positive about
      their experiences using the SARP. They reported lack of costs, friendly programme
      staff, accompaniment to and interpretation at the providing facility, and safety
      of services as key features. Financial and legal circumstances shaped access to
      the programme and women learned about the SARP through word-of-mouth and
      community workshops. After accessing the SARP and receiving support, women became
      community advocates for reproductive health. Efforts to expand the programme and
      raise awareness in migrant communities appear warranted. Our findings suggest
      that referral programmes for safe and legal abortion can be successful in
      settings with large displaced and migrant populations. Identifying ways to work
      within legal constraints to expand access to safe services has the potential to
      reduce harm from unsafe abortion even in humanitarian settings.

PMID- 29210342
TI  - Antibiotics potentiating potential of catharanthine against superbug Pseudomonas
      aeruginosa.
AB  - Multidrug resistance (MDR) put an alarming situation like preantibiotic era which
      compels us to invigorate the basic science of anti-infective chemotherapy. Hence,
      the drug resistant genes/proteins were explored as promising drug targets.
      Keeping this thing in mind, proteome of Pseudomonas aeruginosa PA01 was explored,
      which resulted in the identification of tripartite protein complexes (MexA, MexB,
      and OprM) as promising drug target for the screening of natural and synthetic
      inhibitors. The purpose of present investigation was to explore the drug
      resistance reversal potential mechanism of catharanthine isolated from the leaves
      of Catharanthus roseous. Hence, the test compound catharanthine was in silico
      screened using docking studies against the above receptors, which showed
      significant binding affinity with these receptors. In order to validate the in
      silico findings, in vitro evaluation of the test compound was also carried out.
      In combination, catharanthine reduced the minimum inhibitory concentration MIC of
      tetracycline (TET) and streptomycin up to 16 and 8 folds, respectively. Further,
      in time kill assay, catharanthine in combination with TET reduced the cell
      viability in concentration dependent manner and was also able to reduce the
      mutation prevention concentration of TET. It was also deduced that drug
      resistance reversal potential of catharanthine was due to inhibition of the
      efflux pumps.

PMID- 29210343
TI  - Laxative Use in the Setting of Positive Testing for Clostridium difficile
      Infection.

PMID- 29210344
TI  - Battling Entropy in Infection Control Systems.

PMID- 29210345
TI  - Twitter Me This-Can Social Media Revolutionize Academic Medicine?

PMID- 29210346
TI  - Serious Neurological Adverse Events after Ivermectin-Do They Occur beyond the
      Indication of Onchocerciasis?
AB  - Serious neurological adverse events have been reported from large scale community
      based ivermectin treatment campaigns against Onchocerciasis volvulus in Africa.
      The mechanism of these events has been debated in the literature, largely
      focusing on the role of concomitant infection with Loa loa versus the presence of
      mdr-1 gene variants in humans allowing ivermectin penetration into the central
      nervous system. A case series of serious neurological adverse events occurring
      with the use of ivermectin outside of the onchocerciasis indication has been
      identified in VigiBase, an international database of suspected adverse drug
      reactions. Forty-eight cases have been reported from multiple countries in which
      ivermectin has been prescribed for multiple indications; clinical review excluded
      20 cases with more probable explanations or other exclusion criteria. Within the
      remaining 28 cases, there is supportive evidence for a causative role of
      ivermectin including presence of the drug in brain tissue in one case and
      recurrence of symptoms on repeated exposure in three cases. This series suggests
      that serious neurological adverse events observed with the use of ivermectin in
      the treatment of onchocerciasis may not be entirely explained by concomitant high
      burden loiasis infections. By comparison with the extensive post marketing
      experience with ivermectin in the successful treatment of parasitic infections,
      the number of reported cases suggests that such events are likely rare. However,
      elucidation of individual-level risk factors could contribute to therapeutic
      decisions that can minimize harms. Further investigation into the potential for
      drug-drug interactions and explorations of polymorphisms in the mdr-1 gene are
      recommended.

PMID- 29210347
TI  - Visceral Leishmaniasis and HIV Co-Infection in Northwest Ethiopia: Antiretroviral
      Treatment and Burden of Disease among Patients Enrolled in HIV Care.
AB  - The approach to treatment of visceral leishmaniasis (VL)-HIV co-infection in East
      Africa has not been systematically examined. Although antiretroviral treatment
      (ART) should be initiated for all co-infected persons, the extent of ART
      prescription is not known. We conducted a retrospective cohort study including
      all VL-HIV co-infected adults at selected referral and district hospitals in
      northwest Ethiopia from 2010 to 2015. Purposes of the study were to compare the
      proportion of VL diagnoses made in previously diagnosed HIV-patients versus
      diagnosis concurrent with HIV diagnosis and to quantify utilization of ART. We
      included 112 patients and 58 patients at the referral and district hospital,
      respectively (median age: 30 years, 98% males). Of all VL cases, 56% (63/112) and
      19% (11/58) occurred in known HIV patients at the referral and district hospital,
      respectively, with a median CD4 count at VL diagnosis of 45 cells/uL and 248
      cells/uL at the referral and district hospital, respectively. Seventy-six percent
      (56/44) were on ART at VL diagnosis and nine (12%) started ART after VL
      diagnosis. The remaining 96 (56%) patients had both infections diagnosed
      concurrently, with a median CD4 count of 56 and 143 cells/uL at the referral and
      district hospital, respectively. Among cured patients, ART initiation was 67% and
      36% at the referral and district hospital, respectively. A substantial proportion
      of VL-HIV cases occur while in HIV care, requiring further evaluation of
      preventive strategies. Among newly diagnosed VL-HIV co-infected patients, ART
      initiation was low. The reasons, including poor documentation and information
      exchange, should be assessed.

PMID- 29210348
TI  - Mediating Effect of Repeated Tuberculosis Exposure on the Risk of Transmission to
      Household Contacts of Multidrug-Resistant Tuberculosis Patients.
AB  - Primary Mycobacterium tuberculosis transmission is an important driver of the
      global epidemic of resistance to tuberculosis drugs. A few studies have compared
      tuberculosis infection in contacts of index cases with different drug-resistant
      profiles, suggesting that contacts of multidrug-resistant (MDR) tuberculosis
      cases are at higher risk. Repeated tuberculosis exposure in contacts of MDR
      tuberculosis patients through recurrent tuberculosis may modify this
      relationship. We compared tuberculosis infection in household contacts of MDR and
      drug-susceptible (DS) tuberculosis patients from six cities in southeastern China
      and investigated whether repeated tuberculosis exposure was a mediating factor.
      Tuberculosis infection was defined as a tuberculin skin test induration >= 10 mm.
      In all, 111 (28.0%) of 397 household contacts of MDR tuberculosis patients and
      165 (24.7%) of 667 contacts of DS tuberculosis index cases were infected with
      tuberculosis. In a multivariate model not including the previous tuberculosis
      exposure, contacts of MDR tuberculosis patients had a higher likelihood of
      tuberculosis infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval
      [CI] = 1.01-1.84; P = 0.041). In a separate multivariate model adjusted for the
      previous tuberculosis exposure, the odds ratio of tuberculosis infection flipped
      and contacts of MDR cases were now at lower risk for tuberculosis infection (AOR
      = 0.55; 95% CI = 0.38-0.81; P = 0.003). These findings suggest prior tuberculosis
      exposure in contacts strongly mediates the relationship between tuberculosis
      infection and the index drug resistance profile. Prior studies showing lower risk
      of developing tuberculosis among contacts of MDR tuberculosis patients may be
      partially explained by a lower rate of tuberculosis infection at baseline.

PMID- 29210349
TI  - High Prevalence of Shigella or Enteroinvasive Escherichia coli Carriage among
      Residents of an Internally Displaced Persons Camp in South Sudan.
AB  - Displaced persons living in camps are at an increased risk of diarrheal diseases.
      Subclinical carriage of pathogens may contribute to the spread of disease,
      especially for microbes that require a low infectious dose. Multiplex real-time
      polymerase chain reaction was performed to detect a panel of 20 bacterial, viral,
      and protozoal targets, and we report a high prevalence of enteropathogen
      carriage, including Shigella spp. or enteroinvasive Escherichia coli in 14%,
      among a sample of 88 asymptomatic individuals in an internally displaced persons
      camp in South Sudan. Further studies are needed to determine the contribution of
      such carriage to the spread of disease.

PMID- 29210350
TI  - Rotavirus Vaccine will Improve Child Survival by More than Just Preventing
      Diarrhea: Evidence from Bangladesh.
AB  - Despite the high burden of rotavirus diarrhea, uptake of rotavirus vaccines in
      Asia remains low. This primarily stems from a perception of rotavirus as a non
      life-threatening pathogen amidst a background of competing health priorities and
      limited resources. In the largest pediatric hospital of Bangladesh, where there
      is a fierce competition for beds, we found that between November 2015 and October
      2016, 12% of 23,064 admissions were due to gastrointestinal infections, 54% of
      which were caused by rotavirus. One in four cases requiring hospitalization, or
      5,879 cases, was refused because of unavailability of beds. Most refused cases
      were of pneumonia (22%), severe perinatal asphyxia (17%), preterm birth
      complications (7%), and meningitis (2%), all of which bear high risks of death or
      disability, if not treated timely. When determining vaccine policies and
      conducting vaccine impact studies, it would be shortsighted to not consider the
      impact on morbidity and mortality of cases that are refused admission because of
      the hospitalization of children with a preventable disease as rotavirus diarrhea.
      In our hospital, routine use of a rotavirus vaccine with 41% efficacy will
      release 629 beds per year to accommodate previously refused cases. Based on
      evidence, we make the case that introduction of this vaccine in Bangladesh and
      the surrounding region will prevent morbidity and mortality, both directly and
      indirectly, and help us ensure survival and well-being of all children.

PMID- 29210351
TI  - Seasonal Dynamics of Malaria in Pregnancy in West Africa: Evidence for Carriage
      of Infections Acquired Before Pregnancy Until First Contact with Antenatal Care.
AB  - In malaria-endemic areas, Plasmodium falciparum prevalence is often high in young
      women because of 1) low use of insecticide-treated nets before their first
      pregnancy and 2) acquired immunity, meaning infections are asymptomatic and thus
      untreated. Consequently, a common source of malaria in pregnancy (MiP) may be
      infected women becoming pregnant, rather than pregnant women becoming infected.
      In this study, prevalence of infection was determined by microscopy at first
      antenatal care (ANC) visit in primigravidae and secundigravidae in Ghana, Burkina
      Faso, Mali, and The Gambia, four countries with strong seasonal variations in
      transmission. Duration of pregnancy spent in the rainy season and other risk
      factors for infection were evaluated using multivariable Poisson regression. We
      found that the overall prevalence of malaria at first ANC was generally high and
      increased with time spent pregnant during the rainy season: prevalence among
      those with the longest exposure was 59.7% in Ghana, 56.7% in Burkina Faso, 42.2%
      in Mali, and 16.8% in Gambia. However, the prevalence was substantial even among
      women whose entire pregnancy before first ANC had occurred in the dry season:
      41.3%, 34.4%, 11.5%, and 7.8%, respectively, in the four countries. In
      multivariable analysis, risk of infection was also higher among primigravidae,
      younger women, and those of lower socioeconomic status, independent of
      seasonality. High prevalence among women without exposure to high transmission
      during their pregnancy suggests that part of the MiP burden results from long
      duration infections, including those acquired preconception. Prevention of
      malaria before pregnancy is needed to reduce the MiP burden.

PMID- 29210353
TI  - Genetic Clustering of Tuberculosis in an Indigenous Community of Brazil.
AB  - We conducted a population-based study of tuberculosis (TB) from 2009 to 2015 in
      an indigenous community of Brazil, the largest in the country, to investigate
      risk factors associated with recent TB transmission. The clinical isolates of
      Mycobacterium tuberculosis were genotyped by IS6110-RFLP (restriction fragment
      length polymorphism) and spoligotyping analysis. Among 67 isolates typed by RFLP,
      69% fell into fifteen clusters, and 91% of TB cases with shared IS6110-RFLP
      pattern were diagnosed within 2 years of another case in the cluster. Individual
      risk factors associated with genetic clustering were domestic overcrowding (odds
      ratio [OR]: 6.10; 95% confidence interval [CI]: 1.50-24.88) and low social class
      (OR: 3.72; 95% CI: 1.00-13.98). Most reported contacts (76%) were identified
      within the household of the index TB case, but most of the genetic clustering of
      M. tuberculosis occurred outside of household (79%). Expanded contacts
      investigation and prophylaxis outside of household should be considered as a
      priority for TB control programs in this population.

PMID- 29210352
TI  - Congenital Transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico:
      An Observational Prospective Study.
AB  - Compared with South America, there is a lack of epidemiologic studies about the
      risk of congenital transmission of Trypanosoma cruzi in Central America and
      Mexico. It has been suggested that T. cruzi genotypes might differ by region and
      that congenital transmission might vary according to the parasite's genotype. Our
      objective was to compare T. cruzi congenital transmission rates in three
      countries. We performed an observational prospective study in 2011-2014 enrolling
      women at delivery in one hospital in Argentina, two hospitals in Honduras, and
      two hospitals in Mexico. Congenital T. cruzi infection was defined as the
      presence of one or more of the following criteria: presence of parasites in cord
      blood (direct parasitological microscopic examination) with positive polymerase
      chain reaction (PCR) in cord blood, presence of parasites in infant's blood at 4
      8 weeks (direct parasitological microscopic examination), and persistence of T.
      cruzi-specific antibodies at 10 months, as measured by at least two tests. Among
      28,145 enrolled women, 347 had at least one antibody rapid test positive in cord
      blood and a positive enzyme-linked immunosorbent assay in maternal blood. PCR in
      maternal blood was positive in 73.2% of the cases, and genotyping identified a
      majority of non-TcI in the three countries. We found no (0.0%; 95% confidence
      interval [CI]: 0.0, 2.0) confirmed congenital case in Honduras. Congenital
      transmission was 6.6% (95% CI: 3.1, 12.2) in Argentina and 6.3% (95% CI: 0.8,
      20.8) in Mexico. Trypanosoma cruzi non-TcI predominated and risks of congenital
      transmission were similar in Argentina and Mexico.

PMID- 29210354
TI  - Neurocysticercosis among People Living Near Pigs Heavily Infected with
      Cysticercosis in Rural Endemic Peru.
AB  - Neurocysticercosis causes substantial neurologic morbidity in endemic regions
      around the world. In this cross-sectional study, we describe the frequency of
      neurocysticercosis among a presumed high-risk group of people in an endemic
      community in northern Peru. Participants who screened positive on a nine-question
      seizure survey were evaluated clinically to diagnose epilepsy using International
      League Against Epilepsy criteria. Those with epilepsy were offered a noncontrast
      computerized tomography (CT) of the head. We also tested sera from all
      participants using the lentil lectin-bound glycoprotein enzyme-linked
      immunoelectrotransfer blot (EITB) to detect anti-cysticercus antibodies and
      enzyme-linked immunosorbent assay (ELISA) B60/B158 to detect cysticercosis
      antigens. Participants with strongly positive ELISA (ratio >= 3) were offered a
      noncontrast magnetic resonance imaging (MRI) of the brain. We diagnosed 16 cases
      of epilepsy among 527 people screened (lifetime prevalence 30 per 1,000). Twelve
      with epilepsy accepted CT scan and five (41.7%) had parenchymal calcifications.
      None had viable cysts. Of the 514 who provided a blood sample, 241 (46.9%) were
      seropositive by EITB and 12 (2.9%) were strongly positive by ELISA (ratio >= 3).
      Eleven accepted MRI and eight (72.3%) had neurocysticercosis, including five with
      extraparenchymal cysts, five with parenchymal vesicular cysts, and two with
      parenchymal granulomas. These findings show that clinically relevant forms of
      neurocysticercosis and epilepsy can be found by applying screening interventions
      in communities endemic to Taenia solium. Longitudinal controlled studies are
      needed to better understand which subgroups are at highest risk and which are
      most likely to have improved prognosis as a result of screening.

PMID- 29210355
TI  - Neuroangiostrongyliasis: The "Subarachnoid Phase" and Its Implications for
      Anthelminthic Therapy.
AB  - Infection with the Rat Lungworm Angiostrongylus cantonensis is the leading cause
      of human eosinophilic meningoencephalitis worldwide. From its origins in
      southeastern Asia, the parasite was spread extensively throughout the twentieth
      century and is now established in many of the world's warmer regions. Its
      clinical effects range from mild and transient symptoms, usually headache with
      peripheral nerve dysfunction, to severe and permanent central nervous system
      (CNS) damage, occasionally fatal. The severity and prognosis of disease are
      determined by the larval dose, acquired by ingesting infected intermediate hosts
      (slugs and snails) or, less often, paratenic hosts, such as crabs, shrimps,
      frogs, and monitor lizards. Early diagnosis is critical for treatment and depends
      on clinical suspicion, for laboratory confirmation from blood and cerebrospinal
      fluid can be delayed and unreliable. Treatment is fraught with difficulty,
      compounded by conflicting published results. Corticosteroids play a useful role
      in suppressing early CNS inflammation, but their duration for maintenance becomes
      problematic in severe infections. Because most of the pathogenesis results from
      host immuno-inflammatory responses to migrating and dead larvae in the CNS,
      anthelminthic therapy remains controversial: if effective, it kills viable
      larvae, arresting them in the CNS and so exacerbating the pathology. In human
      infections, it is now clear that many larvae do leave the CNS and reach the
      pulmonary arteries, sometimes with clinical consequences. Pioneering life-cycle
      studies in rats demonstrated a "subarachnoid phase" in larval development and
      migration; recent autopsy findings, outlined here, show it also occurs in humans
      and has some bearing on treatment. One new and four previously reported cases of
      human infection are analyzed here, with findings indicating that anthelminthic
      treatment is effective only when given early and should not be commenced beyond 3
      weeks after exposure to infection. In endemic areas, treatment should start as
      soon as this infection is suspected, even without a clear history of exposure,
      given the unacceptable risks of waiting for diagnostic laboratory confirmation.

PMID- 29210356
TI  - Single-molecule studies contrast ordered DNA replication with stochastic
      translesion synthesis.
AB  - High fidelity replicative DNA polymerases are unable to synthesize past DNA
      adducts that result from diverse chemicals, reactive oxygen species or UV light.
      To bypass these replication blocks, cells utilize specialized translesion DNA
      polymerases that are intrinsically error prone and associated with mutagenesis,
      drug resistance, and cancer. How untimely access of translesion polymerases to
      DNA is prevented is poorly understood. Here we use co-localization single
      molecule spectroscopy (CoSMoS) to follow the exchange of the E. coli replicative
      DNA polymerase Pol IIIcore with the translesion polymerases Pol II and Pol IV. We
      find that in contrast to the toolbelt model, the replicative and translesion
      polymerases do not form a stable complex on one clamp but alternate their
      binding. Furthermore, while the loading of clamp and Pol IIIcore is highly
      organized, the exchange with the translesion polymerases is stochastic and is not
      determined by lesion-recognition but instead a concentration-dependent
      competition between the polymerases.

PMID- 29210357
TI  - Structural basis of proton translocation and force generation in mitochondrial
      ATP synthase.
AB  - ATP synthases produce ATP by rotary catalysis, powered by the electrochemical
      proton gradient across the membrane. Understanding this fundamental process
      requires an atomic model of the proton pathway. We determined the structure of an
      intact mitochondrial ATP synthase dimer by electron cryo-microscopy at near
      atomic resolution. Charged and polar residues of the a-subunit stator define two
      aqueous channels, each spanning one half of the membrane. Passing through a
      conserved membrane-intrinsic helix hairpin, the lumenal channel protonates an
      acidic glutamate in the c-ring rotor. Upon ring rotation, the protonated
      glutamate encounters the matrix channel and deprotonates. An arginine between the
      two channels prevents proton leakage. The steep potential gradient over the sub
      nm inter-channel distance exerts a force on the deprotonated glutamate, resulting
      in net directional rotation.

PMID- 29210358
TI  - Computer-aided assessment of breast density: comparison of supervised deep
      learning and feature-based statistical learning.
AB  - Breast density is one of the most significant factors that is associated with
      cancer risk. In this study, our purpose was to develop a supervised deep learning
      approach for automated estimation of percentage density (PD) on digital
      mammograms (DMs). The input 'for processing' DMs was first log-transformed,
      enhanced by a multi-resolution preprocessing scheme, and subsampled to a pixel
      size of 800 um  *  800 um from 100 um  *  100 um. A deep convolutional neural
      network (DCNN) was trained to estimate a probability map of breast density (PMD)
      by using a domain adaptation resampling method. The PD was estimated as the ratio
      of the dense area to the breast area based on the PMD. The DCNN approach was
      compared to a feature-based statistical learning approach. Gray level, texture
      and morphological features were extracted and a least absolute shrinkage and
      selection operator was used to combine the features into a feature-based PMD.
      With approval of the Institutional Review Board, we retrospectively collected a
      training set of 478 DMs and an independent test set of 183 DMs from patient files
      in our institution. Two experienced mammography quality standards act
      radiologists interactively segmented PD as the reference standard. Ten-fold cross
      validation was used for model selection and evaluation with the training set.
      With cross-validation, DCNN obtained a Dice's coefficient (DC) of 0.79  +/-  0.13
      and Pearson's correlation (r) of 0.97, whereas feature-based learning obtained DC
      =  0.72  +/-  0.18 and r  =  0.85. For the independent test set, DCNN achieved
      DC  =  0.76  +/-  0.09 and r  =  0.94, while feature-based learning achieved DC 
      =  0.62  +/-  0.21 and r  =  0.75. Our DCNN approach was significantly better and
      more robust than the feature-based learning approach for automated PD estimation
      on DMs, demonstrating its potential use for automated density reporting as well
      as for model-based risk prediction.

PMID- 29210359
TI  - Leukemia cutis mimicking erythema nodosum or vice versa: A histological
      conundrum.

PMID- 29210360
TI  - Involvement of scars in capecitabine induced hand foot syndrome.

PMID- 29210361
TI  - Successful treatment outcome with itraconazole and potassium iodide in
      disseminated sporotrichosis.

PMID- 29210362
TI  - Giant congenital Becker's nevus overlying a plexiform neurofibroma: Merely a
      coincidence or more than it?

PMID- 29210363
TI  - iNOS- and NOX1-dependent ROS production maintains bacterial homeostasis in the
      ileum of mice.
AB  - The intestinal epithelial cells constitute the first line of defense against gut
      microbes, which includes secretion of various antimicrobial substances. Reactive
      oxygen species (ROS) are well characterized as part of the innate phagocytic
      immunity; however, a role in controlling microorganisms in the gut lumen is less
      clear. Here, we show a role for nitric oxide synthase (iNOS)- and NOX1-produced
      ROS in maintaining homeostasis of the gut microbiota. In vivo imaging revealed
      distinctly high levels of ROS in the ileum of normal healthy mice, regulated in
      accordance with the amount of gut bacteria. The ROS level was dependent on the
      nitric oxide and superoxide producers iNOS and NOX1, respectively, suggesting
      peroxynitrite as the effector molecule. In the ileum of iNOS- and NOX1-deficient
      mice, the bacterial load is increased and the composition is more cecum like. Our
      data suggest a unique role of ileum in maintaining homeostasis of gut microbes
      through production of ROS with potential importance for preventing reflux from
      the large intestine, bacterial overgrowth, and translocation.

PMID- 29210364
TI  - Too Depressed to Swim or Too Afraid to Stop? A Reinterpretation of the Forced
      Swim Test as a Measure of Anxiety-Like Behavior.

PMID- 29210365
TI  - Rethinking JAK2 inhibition: towards novel strategies of more specific and
      versatile Janus kinase inhibition.
AB  - This corrects the article DOI: 10.1038/leu.2017.43.

PMID- 29210366
TI  - Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant
      99 protocol.
AB  - This corrects the article DOI: 10.1038/leu.2015.246.

PMID- 29210367
TI  - Surface enhanced Raman scattering sensor for highly sensitive and selective
      detection of ochratoxin A.
AB  - The trace detection of toxic compounds in complex matrices is a major concern, in
      particular when it comes to mycotoxins in food. We developed a highly sensitive
      and specific SERS sensor for the detection of ochratoxin A using a simple rough
      gold film as a substrate. When adding the analyte, we observed spectral
      variations related to the interaction of the analyte with the specific aptamer
      used as a bioreceptor. Using a partial least squares regression method, our
      sensor is able to detect concentrations down to the picomolar range, which is
      much lower than the minimum legal concentration allowed in food products.
      Moreover, we demonstrate the accurate detection of the analyte in a wide
      concentration range from the picomolar up to the micromolar level. The detection
      was validated with negative detection tests using deoxynivalenol and bovine serum
      albumin.

PMID- 29210368
TI  - Polaron formation mechanisms in conjugated polymers.
AB  - In semiconducting polymers, interactions with conformational degrees of freedom
      can localize charge carriers, and strongly affect charge transport. Polarons can
      form when charges induce deformations of the surrounding medium, including local
      vibrational modes or dielectric polarization. These deformations then interact
      attractively with the charge, tending to localize it. First we investigate
      vibrational polaron formation in poly(3-hexylthiophene) [P3HT], with a tight
      binding model for charges hopping between adjacent rings, coupled to ring
      distortions. We use density functional theory (DFT) calculations to determine
      coupling constants, including the "spring constant" for ring distortions and the
      coupling to the charge carrier. On single chains, we find only broad, weakly
      bound polarons by this mechanism. In 2d crystalline layers of P3HT, even weak
      transverse hopping between chains destabilizes this polaron. Then, we consider
      polarons stabilized by dielectric polarization, described semiclassically with a
      polarizable continuum interacting with the carrier wavefunction. In contrast to
      vibrational polarons, we find dielectrically stabilized polarons in P3HT are
      narrower, more strongly bound, and stable in 2d crystalline layers.

PMID- 29210369
TI  - Signatures of a quantum diffusion limited hydrogen atom tunneling reaction.
AB  - We are studying the details of hydrogen atom (H atom) quantum diffusion in highly
      enriched parahydrogen (pH2) quantum solids doped with chemical species in an
      effort to better understand H atom transport and reactivity under these
      conditions. In this work we present kinetic studies of the 193 nm photo-induced
      chemistry of methanol (CH3OH) isolated in solid pH2. Short-term irradiation of
      CH3OH at 1.8 K readily produces CH2O and CO which we detect using FTIR
      spectroscopy. The in situ photochemistry also produces CH3O and H atoms which we
      can infer from the post-photolysis reaction kinetics that display significant
      CH2OH growth. The CH2OH growth kinetics indicate at least three separate
      tunneling reactions contribute; (i) reactions of photoproduced CH3O with the pH2
      host, (ii) H atom reactions with the CH2O photofragment, and (iii) long-range
      migration of H atoms and reaction with CH3OH. We assign the rapid CH2OH growth to
      the following CH3O + H2 -> CH3OH + H -> CH2OH + H2 two-step sequential tunneling
      mechanism by conducting analogous kinetic measurements using deuterated methanol
      (CD3OD). By performing photolysis experiments at 1.8 and 4.3 K, we show the post
      photolysis reaction kinetics change qualitatively over this small temperature
      range. We use this qualitative change in the reaction kinetics with temperature
      to identify reactions that are quantum diffusion limited. While these results are
      specific to the conditions that exist in pH2 quantum solids, they have direct
      implications on the analogous low temperature H atom tunneling reactions that
      occur on metal surfaces and on interstellar grains.

PMID- 29210370
TI  - Telechelic polymers from reversible-deactivation radical polymerization for
      biomedical applications.
AB  - The main strategies for the design of telechelic polymers synthesized by
      reversible-activation radical polymerization for biomedical applications are
      covered spanning from drug delivery and targeting to theranostics and sensing.

PMID- 29210371
TI  - Hierarchical CuCo2S4 nanoarrays for high-efficient and durable water oxidation
      electrocatalysis.
AB  - It is highly attractive to design and develop earth-abundant electrocatalysts
      toward high-efficiency water oxidation electrocatalysis in alkaline media. In
      this communication, we report the in situ hydrothermal sulfidization preparation
      of a hierarchical CuCo2S4 nanoarray on copper foam (CuCo2S4/CF) from its CuCo2
      hydroxide nanowire array precursor. When used as a 3D catalyst electrode for
      water oxidation, the as-prepared CuCo2S4/CF is superior in catalytic activity,
      demanding overpotentials of only 259 and 295 mV to achieve 60 and 100 mA cm-2 in
      1.0 M KOH, respectively. Moreover, it also shows strong electrochemical
      durability with high turnover frequency values of 0.069 and 0.390 mol O2 s-1 at
      overpotentials of 300 and 400 mV, respectively.

PMID- 29210372
TI  - Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for
      tumor-targeting T1 magnetic resonance imaging contrast agent.
AB  - Endogenous biomaterials in organisms, with native biocompatibility and
      biodegradability, appear more advantageous in the development of nanoscale
      diagnostic and therapeutic systems for future clinical translation. Herein, a
      novel tumor-targeting Magnetic Resonance Imaging (MRI) contrast agent was
      developed based on Mn2+-chelating ultrasmall water-soluble melanin nanoparticles
      (MNP-PEG-Mn). The nanoparticles, with a size of about 5.6 nm, presented high
      chelation stability and showed negligible cytotoxicity as estimated by MTT assay.
      Moreover, the r1 longitudinal relaxivity (20.56 mM-1 s-1) of MNP-PEG-Mn was much
      higher than that of Gadodiamide (6.00 mM-1 s-1), which is a clinically approved
      MRI contrast agent. In vivo MRI experiments revealed excellent tumor-targeting
      specificity after tumor-bearing mice were intravenously injected with MNP-PEG-Mn.
      Additionally, MNP-PEG-Mn could be excreted via renal and hepatobiliary pathways
      with negligible toxicity to body tissues. These preliminary results indicated the
      clinically translatable potential of MNP-PEG-Mn as a T1 MRI contrast agent for
      tumor-targeted imaging.

PMID- 29210373
TI  - Enhanced cell adhesion on a bio-inspired hierarchically structured polyester
      modified with gelatin-methacrylate.
AB  - Herein, fabrication and modification of novel bio-inspired microwell arrays with
      nanoscale topographic structures are reported. The natural nano- and
      microstructures present on the surface of rose petals were hypothesized to
      enhance cell-surface contacts. Thus hierarchically structured polyethylene
      terephthalate glycol modified (PETG) substrates were fabricated by replication
      from rose petals via nanoimprint lithography, followed by covalent modification
      and crosslinking with RGD-presenting gelatin-methacrylate (GelMA) for promoting
      cell adhesion and spreading. Cell culture experiments showed that the
      introduction of gelatin resulted in significantly enhanced cell adhesion and more
      than doubled cell areas on the GelMA modified surfaces. In addition, a slight
      preference was observed for concave compared to convex surfaces, which is
      tentatively attributed to the matching curvature of the micro-cavities and the
      cells, facilitating the accommodation of cells. These bioinspired hierarchically
      structured and gelatin functionalized substrates may provide new prospects for
      designing cell-based interfaces for advanced biomedical studies, e.g. for cell
      culture and biosensing in the future.

PMID- 29210374
TI  - A novel red-emitting K2Ca(PO4)F:Eu2+ phosphor with a large Stokes shift.
AB  - We report a K2CaPO4F:Eu2+ phosphor with a new crystal structure. This phosphor
      has a large Stokes shift and converts near-ultraviolet light to red luminescence
      without absorption of other visible light. The mechanism was elucidated by
      applying a constrained density functional theory to the solved crystal structure.

PMID- 29210375
TI  - A chiral scandium-complex-catalyzed asymmetric inverse-electron-demand oxa-Diels
      Alder reaction of o-quinone methides with fulvenes.
AB  - A highly efficient asymmetric inverse-electron-demand oxa-Diels-Alder reaction of
      o-quinone methides with fulvenes has been realized using a chiral N,N'
      dioxide/Sc(iii) complex as the catalyst. The corresponding optically active
      chromane derivatives were obtained in high yields with excellent dr and ee values
      (up to 99% yield, >19 : 1 dr and 94% ee).

PMID- 29210376
TI  - Selective transformation of carbon dioxide into lower olefins with a bifunctional
      catalyst composed of ZnGa2O4 and SAPO-34.
AB  - A bifunctional catalyst composed of ZnGa2O4 with a spinel structure and molecular
      sieve SAPO-34 catalyses the direct conversion of CO2 to C2-C4 olefins with a
      selectivity of 86% and a CO2 conversion of 13% at 370  degrees C. The oxygen
      vacancies on ZnGa2O4 surfaces are responsible for CO2 activation, forming a
      methanol intermediate, which is then converted into C2-C4 olefins in SAPO-34.

PMID- 29210377
TI  - Palladium-catalyzed oxidative allylation of bis[(pinacolato)boryl]methane:
      synthesis of homoallylic boronic esters.
AB  - A palladium-catalyzed oxidative allylation of bis[(pinacolato)boryl]methane to
      afford the corresponding homoallylic organoboronic esters with moderate to
      excellent yields is reported. This novel transformation provides an efficient
      strategy for the construction of homoallylic organoboronic esters in one step
      with a broad substrate scope. It is proposed that the palladium-catalyzed
      oxidative allylic C-H bond activation process may be involved in the catalytic
      cycle.

PMID- 29210378
TI  - Continuous purification of active pharmaceutical ingredients utilizing polymer
      membrane surface wettability.
AB  - Continuous processing of pharmaceuticals opens opportunities for continuous
      separation based on wettability of polymer membranes. Dual use of hydrophobic and
      hydrophilic membranes realize in-line liquid-liquid extraction in the synthesis
      of four essential APIs. A secondary membrane with opposite wetting
      characteristics proves critical to phase separation of aqueous-organic reaction
      streams.

PMID- 29210379
TI  - Porous dipeptide crystals as volatile-drug vessels.
AB  - Porous crystalline dipeptides absorb, reversibly from the gas phase, a series of
      volatile fluorinated ethers in use as anesthetics. Their vapor pressure was
      considerably reduced, with favorable guest capture and release. Variable channel
      sizes were customized for selective sorption and pressure thresholds were
      observed in the narrowest pores. 1H, 13C and 19F MAS NMR coupled with ab initio
      conformational analysis and grand canonical Monte Carlo simulations highlight the
      guest loading and arrangement adopted in the congruent nanochannels, suggesting
      how the anesthetics can accommodate in biochemical receptors.

PMID- 29210380
TI  - Construction of magnetically separable NiAl LDH/Fe3O4-RGO nanocomposites with
      enhanced photocatalytic performance under visible light.
AB  - Magnetic NiAl layered doubled hydroxide (LDH)/Fe3O4-RGO composites were
      successfully synthesized via a simple hydrothermal route. The as-prepared samples
      were well characterized by X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM) and
      transmission electron microscopy (TEM). The results showed that NiAl LDH
      nanoplatelets and Fe3O4 nanoparticles sized around 15 nm were uniformly anchored
      on the surface of graphene sheets. The NiAl LDH/Fe3O4-RGO25 photocatalyst was
      employed to degrade ciprofloxacin (CIP) in an aqueous solution under visible
      light irradiation. It exhibited enhanced photocatalytic activity compared to pure
      NiAl LDH, the degradation rate of the as-prepared NiAl LDH/Fe3O4-RGO25 was 1.5
      and even 3 times faster than that of NiAl LDH/RGO25 and pure NiAl LDH,
      respectively. This enhancement of photocatalytic activity is attributed to the
      addition of graphene and Fe3O4 NPs, which both efficiently promote the separation
      of charge carriers and improve the optical absorption properties, synergistically
      facilitating the photocatalysis process. Furthermore, the NiAl LDH/Fe3O4-RGO25
      photocatalyst was magnetically separable and exhibited stable catalytic activity,
      which is beneficial to its practical application.

PMID- 29210381
TI  - Simple and rapid detection of bacteria using a nuclease-responsive DNA probe.
AB  - We demonstrate simple and rapid bacterial detection using a nuclease-responsive
      DNA probe. The probe consisting of a fluorescent dye and a quencher at the 5' and
      3' termini, respectively, was designed to be cleaved by nucleases such as
      endonucleases, exonucleases, and DNases, which are released from bacteria using
      an optimized lysis buffer. The fluorescence signal of the cleaved DNA probe
      correlates with the number of Gram-negative Escherichia coli and Gram-positive
      Staphylococcus aureus, and the detection limit was 103 CFU for E. coli and 104
      CFU for S. aureus. Moreover, this method is specific for live bacteria and takes
      just one minute to get the signal including sample collection. These features
      make the present bacterial detection method a powerful on-site bacterial
      contamination assay which is simple, rapid, and quantitative.

PMID- 29210382
TI  - Structure-dependent luminescence of tetra-(4-pyridylphenyl)ethylene: a first
      principles study.
AB  - Luminescent materials with tunable wavelengths have been attracting much
      attention due to their many promising applications. In the present work, the
      recently reported supramolecular coordination complexes of tetra-(4
      pyridylphenyl)ethylene (TPPE) that produce variable-wavelength light emissions
      were investigated by time-dependent density functional theory (TDDFT)
      calculations. We discovered that variations in the luminescent wavelength of TPPE
      mainly depend on the structural deviations from molecular planarity, which affect
      the molecular orbital wavefunction distribution. An interesting trigonometric
      functional relationship between the emission wavelength (the emission energy) and
      the dihedral angle defining deviations from molecular planarity was uncovered.
      The solvent effect was also considered to reveal the mechanism of the solvent
      dependent fluorescence color. These findings may be helpful to rational molecular
      design for high-performance luminescent materials with tunable color.

PMID- 29210383
TI  - Binding energies of hydrated cobalt(ii) by collision-induced dissociation and
      theoretical studies: evidence for a new critical size.
AB  - The experimental sequential bond energies for loss of water from Co2+(H2O)x
      complexes, x = 5-11, are determined by threshold collision-induced dissociation
      (TCID) using a guided ion beam tandem mass spectrometer with a thermal
      electrospray ionization source. Kinetic energy dependent TCID cross sections are
      analyzed to yield 0 K thresholds for sequential loss of neutral water molecules.
      The thresholds are converted from 0 to 298 K values to give hydration enthalpies
      and free energies. Theoretical geometry optimizations and single point energy
      calculations at several levels of theory are performed for the reactant and
      product ion complexes. Theoretical bond energies for ground structures are used
      for direct comparison with experimental values to obtain structural information
      on these complexes. In addition, the dissociative charge separation process,
      Co2+(H2O)x -> CoOH+(H2O)m + H+(H2O)x-m-1, is observed at x = 4, 6, and 7 in
      competition with primary water loss products. Energies for the charge separation
      rate-limiting transition states are calculated and compared to experimental
      threshold measurements. Results suggest that the critical size for which charge
      separation is energetically favored over water loss is xcrit = 6, in contrast to
      lower values in previous literature reports.

PMID- 29210384
TI  - Structures and infrared spectra of calcium phosphate clusters by ab initio
      methods with implicit solvation models.
AB  - Since the first detection of pre-nucleation clusters during the formation of
      calcium phosphate minerals, determining such clusters' compositions and
      structures has become crucial for understanding the early-stage nucleation of
      these minerals in solutions. In previous experimental studies, the composition
      and sizes of pre-nucleation clusters have been calculated, but their structural
      information has been difficult to determine because they are very small (<1 nm).
      In this study, we examined the structures and infrared spectra of small- and
      medium-sized calcium phosphate clusters using ab initio calculations combined
      with implicit solvation models. Adding solvent effects increased the possibility
      of the existence of alternative configurations of calcium phosphate clusters
      other than their compact configurations. The calcium atoms had a tendency to be
      located outside of the clusters to coordinate with water molecules in the aqueous
      environment. The computed infrared spectra of extended small calcium phosphate
      clusters captured some of the features measured in the in situ infrared spectra,
      which supports the network structures proposed by large-scale molecular dynamics
      studies and X-ray adsorption near-edge spectra. The relative stabilities of
      medium-sized Ca9(PO4)6 clusters with respect to the stability of Posner's cluster
      in water were also reviewed. We found that in water, alternative structures with
      low symmetry or large dipole moments had lower energies than Posner's cluster.

PMID- 29210385
TI  - Lighting-up protein-ligand interactions with fluorescent PET (photoinduced
      electron transfer) sensor designs.
AB  - The fluorescence of sensors 1 and 6, which are designed in terms of photoinduced
      electron transfer (PET), is switched 'on' by factors of 15 and 6 with avidin in a
      rather selective manner. Sensors 3 and 7, simpler derivatives of 1, are switched
      'on' by factors of 16 and 7.5 with bovine serum albumin, though at 30-fold higher
      concentrations.

PMID- 29210386
TI  - Platinum for hydrogen sensing: surface and grain boundary scattering antagonistic
      effects in Pt@Au core-shell nanoparticle assemblies prepared using a Langmuir
      Blodgett method.
AB  - Hydrogen resistive sensors are fabricated through the synthesis of a series of
      Pt@Au core-shell nanoparticles showing various Pt shell thicknesses. Resulting
      colloids are assembled as hexagonal close-packed 2D monolayers of various
      dimension characteristics using a simple Langmuir-Blodgett method. The fabricated
      sensors show attractive hydrogen sensing performances with reversible responses
      in extended sensing ranges, a good specificity towards H2, short response and
      recovery times... Sensing measurements and data analyses allow the demonstration
      of the associated sensing mechanisms. The dissociative chemisorption of H2 and O2
      on the Pt surface through a Langmuir-Hinshelwood mechanism leads to the formation
      of chemisorbed hydrogen and hydroxyl groups. This surface nature change induces
      the modification of the scattering of the conduction electrons at both the grain
      surface and intercontacts, tuned by the extent of hydrogen and hydroxyl group
      coverages. In assemblies made of particles showing thin Pt shells, the
      predominance of the surface scattering described by the Fuchs-Sondheimer model
      accounts for the observed conductive responses as the number of involved grain
      boundaries is limited. In contrast, in assemblies made of particles with thick Pt
      shells, the scattering at the grain boundaries described by the Mayadas-Shatzkes
      model mostly contributes to the observed resistive responses. The sensor behavior
      is balanced by these two antagonistic effects.

PMID- 29210387
TI  - The effect of hydronium ions on the structure of phospholipid membranes.
AB  - This work seeks to identify the mechanisms by which hydronium ions (H3O+)
      modulate the structure of phospholipid bilayers by studying the interactions of
      H3O+ with phospholipids at the molecular level. For this, we carried out multiple
      microsecond-long unrestrained molecular dynamics (MD) simulations of a POPC
      bilayer at different H3O+ concentrations. The results show that H3O+ accumulates
      at the membrane surface where it displaces water and forms strong and long-lived
      hydrogen bonds with the phosphate and carbonyl oxygens in phospholipids. This
      results in a concentration-dependent reduction of the area per lipid and an
      increase in bilayer thickness. This study provides an important molecular-level
      insight into the mechanism of how H3O+ modulates the structure of biological
      membranes and is a critical step towards a better understanding of the effect of
      low pH on mammalian and bacterial membranes.

PMID- 29210388
TI  - Vibrational energy relaxation dynamics of diatomic molecules inside superfluid
      helium nanodroplets. The case of the I2 molecule.
AB  - The vibrational energy relaxation (VER) of a homonuclear diatomic molecule (X2)
      in a 4He superfluid nanodroplet (HeND; T = 0.37 K) was studied adapting
      appropriately a hybrid theoretical quantum approach recently proposed by us. In
      the first application the interesting case of the I2(X) molecule was examined
      and, as far as we know, this corresponds to the first theoretical investigation
      on the VER of molecules embedded in HeND. Vibrational relaxation of I2 takes
      place according to a cascade mechanism [sequential transitions between two
      consecutive vibrational levels (nu -> nu - 1; nu - 1 -> nu - 2; ...; 2 -> 1; 1 ->
      0), where an arbitrary relaxation, e.g., nu - 1 -> nu - 2, can only occur once
      the previous relaxation has taken place, and so on]. The global relaxation from
      the initial excited state nu down to the ground state (nu = 0) happens on the
      nanosecond scale. Data on the VER of molecules in HeND are very scarce and a
      vibrational lifetime not far from the I2 one for nu = 1 has been estimated
      experimentally for Na3(24E') on HeND (a qualitatively similar 0 -> 1 vibrational
      energy gap occurs in both species), but metastability has not been reported in
      the second case. The cascade mechanism was understood once the values of the
      coupling matrix elements were examined, and the time evolution of the populations
      of two consecutive vibrational levels was adequately described using a non-linear
      two-state Hamiltonian model for I2 in the HeND. According to the calculations,
      superfluid liquid helium is very efficient in releasing the excess of energy
      arising from the I2 vibrational de-excitation, as it should be. However, the
      number of He atoms evaporated is small compared to what is expected. We hope that
      this first theoretical work on the molecular VER dynamics in HeND will encourage
      researchers to investigate this important process about which we still know very
      little.

PMID- 29210389
TI  - Correction: Probing keto-enol tautomerism using photoelectron spectroscopy.
AB  - Correction for 'Probing keto-enol tautomerism using photoelectron spectroscopy'
      by Nathalie Capron et al., Phys. Chem. Chem. Phys., 2015, 17, 19991-19996.

PMID- 29210390
TI  - Directing the diffusive motion of fullerene-based nanocars using nonplanar gold
      surfaces.
AB  - A new method for guiding the motion of fullerene and fullerene-based nanocars is
      introduced in this paper. The effects of non-flat substrates on the motion of
      C60, a nanocar and a nanotruck are investigated at different conditions and
      temperatures. Their behavior is studied using two different approaches: analyzing
      the variation in potential energy and conducting all-atom classical molecular
      dynamics simulations. This paper proposes that the use of a stepped substrate
      will make their motion more predictable and controllable. The results of the
      simulations show that C60 stays on the top side of the step and cannot jump over
      the step at temperatures of 400 K and lower. However, at temperatures of 500 K
      and higher, C60 has sufficient energy to travel to the down side of the step. C60
      attaches to the edge and moves just alongside of the edge when it is on the down
      side of the step. The edge also restricts the motion of C60 alongside the edge
      and reduces its range of motion. By considering the motion of C60, the general
      behavior of the nanocar and nanotruck is predictable. The nanocar stays on the
      top side of the step at temperatures of 400 K and less; at 500 K and higher
      temperatures, its wheels jump off the edge, and its range of motion is
      restricted. The relatively rigid chassis of the nanotruck does not allow the free
      individual motion of the wheels. As a result, the entire nanotruck stays on the
      top side of the step, even at 600 K. A pathway with the desired route can be
      fabricated for the motion of C60 and nanocars using the method presented in this
      paper. This represents a step towards the directional motion of C60 and nanocars.

PMID- 29210391
TI  - Photoelectron spectroscopy and density functional theory studies of (FeS)mH- (m =
      2-4) cluster anions: effects of the single hydrogen.
AB  - Single hydrogen containing iron hydrosulfide cluster anions (FeS)mH- (m = 2-4)
      are studied by photoelectron spectroscopy (PES) at 3.492 eV (355 nm) and 4.661 eV
      (266 nm) photon energies, and by Density Functional Theory (DFT) calculations.
      The structural properties, relative energies of different spin states and
      isomers, and the first calculated vertical detachment energies (VDEs) of
      different spin states for these (FeS)mH- (m = 2-4) cluster anions are
      investigated at various reasonable theory levels. Two types of structural isomers
      are found for these (FeS)mH- (m = 2-4) clusters: (1) the single hydrogen atom
      bonds to a sulfur site (SH-type); and (2) the single hydrogen atom bonds to an
      iron site (FeH-type). Experimental and theoretical results suggest such available
      different SH- and FeH-type structural isomers should be considered when
      evaluating the properties and behavior of these single hydrogen containing iron
      sulfide clusters in real chemical and biological systems. Compared to their
      related, respective pure iron sulfur (FeS)m- clusters, the first VDE trend of the
      diverse type (FeS)mH0,1- (m = 1-4) clusters can be understood through (1) the
      different electron distribution properties of their highest singly occupied
      molecular orbital employing natural bond orbital analysis (NBO/HSOMO), and (2)
      the partial charge distribution on the NBO/HSOMO localized sites of each cluster
      anion. Generally, the properties of the NBO/HSOMOs play the principal role with
      regard to the physical and chemical properties of all the anions. The change of
      cluster VDE from low to high is associated with the change in nature of their
      NBO/HSOMO from a dipole bound and valence electron mixed character, to a valence
      p orbital on S, to a valence d orbital on Fe, and to a valence p orbital on Fe or
      an Fe-Fe delocalized valence bonding orbital. For clusters having the same
      properties for NBO/HSOMOs, the partial charge distributions at the NBO/HSOMO
      localized sites additionally affect their VDEs: a more negative or less positive
      localized charge distribution is correlated with a lower first VDE. The single
      hydrogen in these (FeS)mH- (m = 2-4) cluster anions is suggested to affect their
      first VDEs through the different structure types (SH- or FeH-), the nature of the
      NBO/HSOMOs at the local site, and the value of partial charge number at the local
      site of the NBO/HSOMO.

PMID- 29210392
TI  - Ultrafast dye regeneration in a core-shell NiO-dye-TiO2 mesoporous film.
AB  - In this study, a core-shell NiO-dye-TiO2 mesoporous film was fabricated for the
      first time, utilizing atomic layer deposition technique and a newly designed
      triphenylamine dye. The structure of the film was confirmed by SEM, TEM, and EDX.
      Excitation of the dye led to efficient and fast charge separation, by hole
      injection into NiO, followed by an unprecedentedly fast dye regeneration (t1/2 <=
      500 fs) by electron transfer to TiO2. The resulting charge separated state showed
      a pronounced transient absorption spectrum caused by the Stark effect, and no
      significant decay was found within 1.9 ns. This indicates that charge
      recombination between NiO and TiO2 is much slower than that between the NiO and
      the reduced dye in the absence of the TiO2 layer (t1/2 ~ 100 ps).

PMID- 29210393
TI  - A high-performance electrochemical supercapacitor based on a polyaniline/reduced
      graphene oxide electrode and a copper(ii) ion active electrolyte.
AB  - Active electrolyte enhanced supercapacitors (AEESCs) have received increasing
      attention because of their large specific capacitance and easy fabrication
      process. The better matching between the active electrolyte and the counter
      electrode and the slow self-discharge rate are the challenges of this type of
      supercapacitor. In this paper, a novel AEESC with polyaniline/reduced graphene
      oxide hydrogel (PANI/RGOHG) as the anode and Cu(ii) ions as the cathodic active
      electrolyte is constructed. Experimental results demonstrate that the electrode
      potentials of PANI and Cu(ii) can match perfectly, thus the device has a wide
      working voltage range. Because of the large specific capacitance of both PANI and
      Cu(ii), a high average specific capacitance of a single electrode of 1120 F g-1
      at 2.6 A g-1 is achieved. Meanwhile, self-discharge is also suppressed because
      the reduction product of Cu(ii) is immobilized on the electrode. These results
      demonstrate that the performance of AEESCs strongly depends on the choice of a
      suitable electrode material, and also reveal that Cu(ii) is a promising cathodic
      active electrolyte for AEESCs.

PMID- 29210394
TI  - Electron and excitation energy transfers in covalently linked donor-acceptor
      dyads: mechanisms and dynamics revealed using quantum chemistry.
AB  - Photoinduced electron transfer (ET), hole transfer (HT), charge recombination
      (CR) and energy transfer (EET) are fundamental mechanisms, which occur in both
      natural and artificial light harvesting systems. Here, we present a computational
      strategy which determines ET, HT, CR and EET rates in a consistent way and merges
      them in a kinetic model to reproduce the net excited state dynamics. The effects
      of the solvent are included in all steps of the calculations making the present
      strategy a useful tool for a rational design of charge and energy transfer
      processes in complex systems. An application to covalently linked zinc and free
      base porphyrin-naphthalenediimide dyads is presented. For each of the two
      systems, ultrafast optical spectroscopy experiments have shown a specific
      photophysics with different processes taking place simultaneously. The model
      reveals that such a diversity is mainly due to the different relative stability
      of the charge-separated state, while the electronic couplings for charge and
      energy transfer processes are quite similar in the two dyads.

PMID- 29210395
TI  - Effect on orthometallation of NHC palladium complexes toward the catalytic
      activity studies in Suzuki coupling reaction.
AB  - Herein, we report an approach to improve catalytic activity for cross-coupling
      reactions. N-Heterocyclic carbene (NHC) palladium complexes bearing a nitrogen
      based ligand without orthometallation complexes show remarkable activities in
      Suzuki coupling reaction than orthometallation. Aryl chlorides examples employed
      in air and ambient temperature in Suzuki coupling reaction to reach completion
      within few minutes.

PMID- 29210396
TI  - Engineering chemical interactions in microbial communities.
AB  - Microbes living within host-associated microbial communities (microbiotas) rely
      on chemical communication to interact with surrounding organisms. These
      interactions serve many purposes, from supplying the multicellular host with
      nutrients to antagonizing invading pathogens, and breakdown of chemical signaling
      has potentially negative consequences for both the host and microbiota. Efforts
      to engineer microbes to take part in chemical interactions represent a promising
      strategy for modulating chemical signaling within these complex communities. In
      this review, we discuss prominent examples of chemical interactions found within
      host-associated microbial communities, with an emphasis on the plant-root
      microbiota and the intestinal microbiota of animals. We then highlight how an
      understanding of such interactions has guided efforts to engineer microbes to
      participate in chemical signaling in these habitats. We discuss engineering
      efforts in the context of chemical interactions that enable host colonization,
      promote host health, and exclude pathogens. Finally, we describe prominent
      challenges facing this field and propose new directions for future engineering
      efforts.

PMID- 29210397
TI  - Recent progress in 2D group-VA semiconductors: from theory to experiment.
AB  - Phosphorene, an emerging two-dimensional material, has received considerable
      attention due to its layer-controlled direct bandgap, high carrier mobility,
      negative Poisson's ratio and unique in-plane anisotropy. As cousins of
      phosphorene, 2D group-VA arsenene, antimonene and bismuthene have also garnered
      tremendous interest due to their intriguing structures and fascinating electronic
      properties. 2D group-VA family members are opening up brand-new opportunities for
      their multifunctional applications encompassing electronics, optoelectronics,
      topological spintronics, thermoelectrics, sensors, Li- or Na-batteries. In this
      review, we extensively explore the latest theoretical and experimental progress
      made in the fundamental properties, fabrications and applications of 2D group-VA
      materials, and offer perspectives and challenges for the future of this emerging
      field.

PMID- 29210398
TI  - DFT calculations for structural prediction and applications of intercalated
      lamellar compounds.
AB  - The intercalated layered materials are commonly built from structures complex
      enough to have large unit cells and, because of this, calculations of their
      electronic structures are very demanding in terms of memory, processing and time.
      Also, the versatility of these compounds enables the synthesis of a large number
      of derived materials difficult to characterize. Only in the last two decades, a
      combination of theoretical methodologies and advances in processing made density
      functional theory (DFT) calculations quite interesting as an investigation tool
      for this family of materials. Since the intercalated layered or lamellar
      compounds correspond to a large group of important classes of materials and their
      experimental data were, and are still being, generated, only a small part of the
      data comes from electronic structure simulations. In this review, we have listed
      some relevant types of intercalated lamellar materials, the useful methodologies
      implemented in the standard suit of codes for DFT calculations and examples of
      the many applications of the calculations to the understanding of physical and
      chemical properties, to the planning of novel materials with desirable
      properties, and even to assist the structural characterization, by simulating
      complex results from nuclear magnetic resonance, vibrational spectroscopy and
      powder X-ray diffraction. In addition to the properties simulated directly as
      observables, other quantities such as density of states, partial charges and
      electronic density difference, provide relevant information about the materials
      and their behavior under diverse physical and chemical conditions. The
      combination of the geometric, electronic and vibrational structures also leads to
      the simulations of thermodynamic potentials, entropy and phase diagrams in the
      solid state. This significant ensemble of research tools makes DFT calculations
      very compelling and useful to gain new insights into innovation developments for
      intercalated lamellar materials.

PMID- 29210399
TI  - An ion-pair receptor comprising urea groups and N-benzyl-aza-18-crown-6:
      effective recognition and liquid-liquid extraction of KCl salt.
AB  - Compound 1 was designed and prepared as a heteroditopic ion-pair receptor that
      contains two urea groups for anion complexation and N-benzyl-18-crown-6 for
      cation recognition. These ion-binding domains are assembled together by the l
      ornithine scaffold. Qualitative cation coordination studies of receptor 1,
      supported by quantitative data received for monotopic N-(3-nitrobenzyl)-aza-18
      crown-6 (3a), have shown that 1 has a strong affinity for Na+, K+ and NH4+
      cations. Anion binding studies revealed that in the absence of cations
      coordinated to 1 (TBA salts), anions are bound with a relatively moderate
      strength with the selectivity: BzO- > AcO- > Cl-> NO2- > Br-. However, in the
      presence of cations coordinated to the N-benzyl-18-crown-6 the anion binding
      affinity increases considerably with the notable exception of carboxylates. For
      example, chloride binding is increased by over five times in the presence of K+
      cations and the selectivity trend for salt binding is: KCl > KOBz > KOAc > KNO2 >
      KBr. Liquid/liquid extraction studies revealed that receptor 1 is an effective
      extractant for KCl and NH4Cl salts from aqueous to organic phase.

PMID- 29210400
TI  - h-BN/graphene van der Waals vertical heterostructure: a fully spin-polarized
      photocurrent generator.
AB  - By constructing transport junctions using graphene-based van der Waals (vdW)
      heterostructures in which a zigzag-edged graphene nanoribbon (ZGNR) is sandwiched
      between two hexagonal boron-nitride sheets, we computationally demonstrate a new
      scheme for generating perfect spin-polarized quantum transport in ZGNRs by light
      irradiation. The mechanism lies in the lift of spin degeneracy of ZGNR induced by
      the stagger potential it receives from the BN sheets and the subsequent
      possibility of single spin excitation of electrons from the valence band to the
      conduction band by properly tuning the photon energy. This scheme is rather
      robust in that we always achieve desirable results irrespective of whether we
      decrease or increase the interlayer distance by applying compressive or tensile
      strain vertically to the sheets or shift the BN sheets in-plane relative to the
      graphene nanoribbons. More importantly, this scheme overcomes the long-standing
      difficulties in traditional ways of using solely electrical field or chemical
      modification for obtaining half-metallic transport in ZGNRs and thus paves a more
      feasible way for their application in spintronics.

PMID- 29210401
TI  - Hybrid magneto-plasmonic liposomes for multimodal image-guided and brain-targeted
      HIV treatment.
AB  - Image-guided drug delivery is an emerging strategy in the field of nanomedicine.
      The addition of image guidance to a traditional drug delivery system is expected
      to achieve highly efficient treatment by tracking the drug carriers in the body
      and monitoring their effective accumulation in the targeted tissues. In this
      study, we developed multifunctional magneto-plasmonic liposomes (MPLs), a hybrid
      system combining liposomes and magneto-plasmonic nanoparticles for a triple
      modality image-guided drug delivery. Tenofovir disoproxil fumarate, an
      antiretroviral drug used to treat human immunodeficiency virus type 1 (HIV-1),
      was encapsulated into the MPLs to enable the treatment in the brain
      microenvironment, which is inaccessible to most of the drugs. We found strong
      negative and positive contrasts originating from the magnetic core of MPLs in
      magnetic resonance imaging (MRI) and magnetic particle imaging (MPI),
      respectively. The gold shell of MPLs showed bright positive contrast in X-ray
      computed tomography (CT). MPLs achieved enhanced transmigration across an in
      vitro blood-brain barrier (BBB) model by magnetic targeting. Moreover, MPLs
      provided desired therapeutic effects against HIV infected microglia cells.

PMID- 29210402
TI  - Unusual response to environmental polarity in a nonlinear-optical benzylidene
      type chromophore containing a 1,3-bis(dicyanomethylidene)indane acceptor
      fragment.
AB  - One of the strongest known electron-accepting fragments used in the synthesis of
      organic dyes for applications in nonlinear optics (NLO) is 1,3
      bis(dicyanomethylidene)indane (BDMI). By studying a benzylidene-type push-pull
      chromophore bearing a 5-carboxy-BDMI electron-acceptor and 4
      (dimethylamino)aniline donor fragment, we demonstrate that this class of
      compounds can show unusual response to the polarity of the surrounding medium.
      The combined results of UV-Vis absorption spectrometry, NMR experiments and
      computational modeling indicate that the studied compound undergoes a geometrical
      transformation that involves an increase in the torsion angle omega between the
      aniline and indane ring systems with the rise of the polarity of the surrounding
      medium. This process is partly facilitated by an increased rotational freedom
      around omega in more polar solvents, as detected experimentally by NMR and
      predicted by calculations. Regarding the practical application aspects,
      computations predict that the solvent-polarity-induced increase of torsion omega
      would lead to a notable decrease in the first hyperpolarizability (beta) value.
      This was detected experimentally, as hyper-Rayleigh scattering (HRS) data showed
      a drop in the compound's NLO activity from betaHRS(532)  = 513 * 10-30 esu in
      toluene to betaHRS(532)  =  249 * 10-30 esu in acetonitrile. This places
      limitations on the NLO applications of the studied compound and its structural
      analogues, as the surrounding medium (solvent of polymer matrix) with the lowest
      possible polarity needs to be used to maximize their NLO efficiency.

PMID- 29210403
TI  - Atomic layer doping of Mn magnetic impurities from surface chains at a Ge/Si
      hetero-interface.
AB  - We realize Mn delta-doping into Si and Si/Ge interfaces using Mn atomic chains on
      Si(001). Highly sensitive X-ray absorption fine structure techniques reveal that
      encapsulation at room temperature prevents the formation of silicides/germanides
      while maintaining one-dimensional anisotropic structures. This is revealed by
      studying both the incident X-ray polarization dependence and post-annealing
      effects. Density functional theory calculations suggest that Mn atoms are located
      at substitutional sites, and show good agreement with experiment. A comprehensive
      magnetotransport study reveals magnetic ordering within the Mn delta-doped layer,
      which is observed at around 120 K. We demonstrate that doping methods based on
      the burial of surface nanostructures allows for the realization of systems for
      which conventional doping methods fail.

PMID- 29210404
TI  - Silica@layered double hydroxide core-shell hybrid materials.
AB  - A series of silica@layered double hydroxides (SiO2@Mg2Al-CO3-AMO-LDHs) have been
      synthesised by in situ precipitation of Mg2Al-CO3-LDH at room temperature in the
      presence of amorphous spherical silica particles (~500 nm). We have
      systematically investigated a number of synthetic parameters in order to evaluate
      their effects on the composition, morphological and physical properties of the
      isolated materials. Syntheses carried out at moderate stirring speeds (e.g. 500
      rpm) were found to promote the formation of vertically aligned LDH platelets with
      respect to the silica surface. Addition rates of the metal solutions slower than
      0.43 mmol h-1 were found to create a thicker LDH shell consisting of vertically
      aligned LDH platelets. When the metal solutions were added rapidly (0.86 mmol h
      1), we observed that for both slow and fast stirring speeds the synthesised core
      shell materials had thin LDH shells and the majority of the LDH precipitated
      independent of the silica, forming unbound "free" LDH.

PMID- 29210405
TI  - Homo-endotaxial one-dimensional Si nanostructures.
AB  - One-dimensional (1D) nanostructures are highly sought after, both for their novel
      electronic properties as well as for their improved functionality. However, due
      to their nanoscale dimensions, these properties are significantly affected by the
      environment in which they are embedded. In this paper, we report on the creation
      of 1D homo-endotaxial Si nanostructures, i.e. 1D Si nanostructures with a lattice
      structure that is uniquely different from the Si diamond lattice in which they
      are embedded. We use scanning tunneling microscopy and spectroscopy, scanning
      transmission electron microscopy, density functional theory, and conductive
      atomic force microscopy to elucidate their formation and properties. Depending on
      kinetic constraints during growth, they can be prepared as endotaxial 1D Si
      nanostructures completely embedded in crystalline Si, or underneath a stripe of
      amorphous Si containing a large concentration of Bi atoms. These homo-endotaxial
      1D Si nanostructures have the potential to be useful components in nanoelectronic
      devices based on the technologically mature Si platform.

PMID- 29210406
TI  - A hydrogen-atom transfer mechanism in the oxidation of alcohols by [FeO4]2- in
      aqueous solution.
AB  - The ferrate(vi) ion, [FeO4]2-, has attracted much interest in recent years
      because of its potential use as a green oxidant in organic synthesis and water
      treatment. Although there have been several reports on the use of ferrate(vi) for
      the oxidation of alcohols to the corresponding carbonyl compounds, the mechanism
      remains unclear. In this work, the kinetics of the oxidation of a series of
      alcohols with alpha-C-H bond dissociation energies ranging from 81 to 95 kcal mol
      1 have been studied by UV/Vis spectrophotometry. The reactions are first-order in
      both [FeO4]2- and [alcohol]. The deuterium isotope effects for the oxidation of
      methanol/d4-methanol, ethanol/d6-ethanol and benzyl alcohol/d7-benzyl alcohol are
      18.0 +/- 0.1, 4.1 +/- 0.1 and 11.2 +/- 0.1, respectively. A linear correlation is
      found between the second-order rate constants and the alpha-C-H bond dissociation
      energies (BDEs) of the alcohols, consistent with a hydrogen atom transfer (HAT)
      mechanism. The proposed HAT mechanism is supported by DFT calculations.

PMID- 29210407
TI  - Three-dimensional vapor intrusion modeling approach that combines wind and stack
      effects on indoor, atmospheric, and subsurface domains.
AB  - Vapor intrusion (IV) exposure risks are difficult to characterize due to the role
      of atmospheric, building and subsurface processes. This study presents a three
      dimensional VI model that extends the common subsurface fate and transport
      equations to incorporate wind and stack effects on indoor air pressure, building
      air exchange rate (AER) and indoor contaminant concentration to improve VI
      exposure risk estimates. The model incorporates three modeling programs: (1)
      COMSOL Multiphysics to model subsurface fate and transport processes, (2) CFD0 to
      model atmospheric air flow around the building, and (3) CONTAM to model indoor
      air quality. The combined VI model predicts AER values, zonal indoor air
      pressures and zonal indoor air contaminant concentrations as a function of wind
      speed, wind direction and outdoor and indoor temperature. Steady state modeling
      results for a single-story building with a basement demonstrate that wind speed,
      wind direction and opening locations in a building play important roles in
      changing the AER, indoor air pressure, and indoor air contaminant concentration.
      Calculated indoor air pressures ranged from approximately -10 Pa to +4 Pa
      depending on weather conditions and building characteristics. AER values, mass
      entry rates and indoor air concentrations vary depending on weather conditions
      and building characteristics. The presented modeling approach can be used to
      investigate the relationship between building features, AER, building pressures,
      soil gas concentrations, indoor air concentrations and VI exposure risks.

PMID- 29210408
TI  - A protected excitation-energy reservoir for efficient upconversion luminescence.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) are of great interest for
      biomedical applications. Currently, the applicability of UCNP bionanotechnology
      is hampered by the generally low luminescence intensity of UCNPs and inefficient
      energy transfer from UCNPs to surface-bound chromophores used e.g. for
      photodynamic therapy or analyte sensing. In this work, we address the low
      efficiency issue by developing versatile core-shell nanostructures, where high
      concentration sensitizers and activators are confined in the core and shell
      region of representative hexagonal NaYF4:Yb,Er UCNPs. After doping concentration
      optimization, the sensitizer-rich core is able to harvest/accumulate more
      excitation energy and generate almost one order of magnitude higher luminescence
      intensity than conventional homogeneously doped nanostructures. At the same time,
      the activator ions located in the shell enable a ~6 times more efficient resonant
      energy transfer from UCNPs to surface-bound acceptor dye molecules due to the
      short distance between donor-acceptor pairs. Our work provides new insights into
      the rational design of UCNPs and will greatly increase the general applicability
      of upconversion nanotechnologies.

PMID- 29210409
TI  - Narcissistic chiral self-sorting of molecular face-rotating polyhedra.
AB  - Narcissistic chiral self-sorting prevailed in the assembly of molecular face
      rotating polyhedra from a C3h building block 5,5,10,10,15,15-hexabutyl-truxene
      2,7,12-tricarbaldehyde and racemic mixtures of 1,2-diamines. Out of 124 possible
      stereoisomers, a pair of racemic polyhedra dominated, wherein (1R,2R)-diamines
      were segregated in AAAA polyhedra and (1S,2S)-diamines in CCCC polyhedra. This
      chiral self-sorting process is regulated by facial non-covalent interactions in
      the polyhedra. In contrast, D3h facial building blocks 1,3,5-tris-(4-formyl
      phenyl)triazine and racemic mixtures of 1,2-diamines assembled into polyhedra
      without facial interactions, and their assembly process did not undergo apparent
      chiral self-sorting.

PMID- 29210410
TI  - Cryogenically probing the surface trap states of single nanowires passivated with
      self-assembled molecular monolayers.
AB  - Optoelectronically probing the trap state density of single nanoscale devices is
      a powerful in situ nondestructive technique that is of significance for
      developing high gain photoconductors by surface engineering. However, the
      previously demonstrated optoelectronic methods are based on the exponential
      transient photoresponse assumption and only trap states in a very narrow bandgap
      region can be probed. In this Letter, we demonstrate a cryogenic technique that
      is capable of measuring the density of surface trap states in the full half
      bandgap without the exponential transient photoresponse assumption. The technique
      is applied to an array of silicon nanowire photoconductors that are fabricated on
      silicon-on-insulator (SOI) wafer by the top-down approach. Diethyl 1
      propylphosphonate (DPP) and hexadecane molecular monolayers are self-assembled on
      silicon nanowire surfaces as the passivation layer in comparison with dry oxide
      passivation. The surface trap state density of the dry oxide passivated nanowires
      exponentially increases from the bandgap center, reaching a peak of ~5 * 1013 cm
      2 eV-1 at 50 meV below the conduction band. The defect state density is
      significantly suppressed after DPP and hexadecane molecules are grafted onto the
      nanowire surfaces via covalent bonds. The experimental observations are
      consistent with the density functional theory calculations.

PMID- 29210411
TI  - Graphene integrated circuits: new prospects towards receiver realisation.
AB  - This work demonstrates a design approach which enables the fabrication of fully
      integrated radio frequency (RF) and millimetre-wave frequency direct-conversion
      graphene receivers by adapting the frontend architecture to exploit the state-of
      the-art performance of the recently reported wafer-scale CVD metal-insulator
      graphene (MIG) diodes. As a proof-of-concept, we built a fully integrated
      microwave receiver in the frequency range 2.1-2.7 GHz employing the strong
      nonlinearity and the high responsivity of MIG diodes to successfully receive and
      demodulate complex, digitally modulated communication signals at 2.45 GHz. In
      addition, the fabricated receiver uses zero-biased MIG diodes and consumes zero
      dc power. With the flexibility to be fabricated on different substrates, the
      prototype receiver frontend is fabricated on a low-cost, glass substrate
      utilising a custom-developed MMIC process backend which enables the high
      performance of passive components. The measured performance of the prototype
      makes it suitable for Internet-of-Things (IoT) and Radio Frequency Identification
      (RFID) systems for medical and communication applications.

PMID- 29210412
TI  - Identification and the molecular mechanism of a novel myosin-derived ACE
      inhibitory peptide.
AB  - The objective of this work was to identify a novel ACE inhibitory peptide from
      myosin using a number of in silico methods. Myosin was evaluated as a substrate
      for use in the generation of ACE inhibitory peptides using BIOPEP and ExPASy
      PeptideCutter. Then the ACE inhibitory activity prediction of peptides in silico
      was evaluated using the program peptide ranker, following the database search of
      known and unknown peptides using the program BIOPEP. In addition, the interaction
      mechanisms of the peptide and ACE were evaluated by DS. All of the tripeptides
      were predicted to be nontoxic. Results suggested that the tripeptide NCW exerted
      potent ACE inhibitory activity with an IC50 value of 35.5 MUM. Furthermore, the
      results suggested that the peptide NCW comes into contact with Zn 701, Tyr 523,
      His 383, Glu 384, Glu 411, and His 387. The potential molecular mechanism of the
      NCW/ACE interaction was investigated. Results confirmed that the higher
      inhibitory potency of NCW might be attributed to the formation of more hydrogen
      bonds with the ACE's active site. Therefore, the in silico method is effective to
      predict and identify novel ACE inhibitory peptides from protein hydrolysates.

PMID- 29210413
TI  - Design, synthesis, and conformational analysis of 3-cyclo-butylcarbamoyl
      hydantoins as novel hydrogen bond driven universal peptidomimetics.
AB  - A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was
      synthesized by a regioselective multicomponent domino process followed by easy
      coupling reactions. Calculations, NMR studies and X-ray analysis show that these
      scaffolds are able to project their side chains similar to common secondary
      structures, such as the alpha-helix and beta-turn, with favourable enthalpic and
      entropic profiles.

PMID- 29210414
TI  - Enhanced and synergistic downregulation of oncogenic miRNAs by self-assembled
      branched DNA.
AB  - miRNAs, a group of small non-coding RNA molecules, regulate the expression of
      many genes involved in various cellular processes. Acute evidence suggests that
      one miRNA can regulate many genes as its targets, while one gene can be targeted
      by many miRNAs that co-operatively regulate the gene. Thus, targeting a single
      miRNA is not sufficient enough to rescue the disease phenotype but it is also
      essential to target multiple miRNAs simultaneously. This inspired us to design a
      novel DNA nanostructure that can concurrently downregulate multiple oncomiRNAs.
      Here we designed a programmable antimiR branched DNA (antimiR-bDNA) nanostructure
      having antimiRNAs for selective binding to oncomiRNAs miRNA-27a, 96 and 182 which
      collectively downregulate FOXO1a expression. The antimiR-bDNAs show enhanced
      stability compared to naked antimiRNAs in serum and are able to knockdown these
      miRNAs with up to ~50% greater repression as compared to antimiRNAs. This
      synergistic miRNA repression leads to the restoration of FOXO1a protein levels
      which in turn inhibit G1-S traversion in cancer cells. To the best of our
      knowledge, this is the first study harnessing the ability of bDNA structures to
      silence multiple miRNAs simultaneously.

PMID- 29210415
TI  - Synthesis of polysubstituted pyridines from oxime acetates using NH4I as a dual
      function promoter.
AB  - Pyridine formation with oxime acetates as the building blocks under metal-free
      conditions is described. Ammonium iodide has proved to be a highly efficient
      promoter for oxime N-O bond reduction and subsequent condensation reactions,
      whereby it played a dual-function role in the transformation. While the three
      component reaction of oxime acetates, benzaldehydes, and 1,3-dicarbonyls
      proceeded well with the assistance of a stoichiometric amount of ammonium iodide,
      the condensation of oximes and acroleins was enabled by using a catalytic
      initiator to afford substituted pyridines. By this protocol, substituted pyridine
      products were generated in moderate to excellent yields with tolerance towards a
      broad range of functional groups.

PMID- 29210416
TI  - Biexciton and trion energy transfer from CdSe/CdS giant nanocrystals to Si
      substrates.
AB  - Observation of energy transfer (ET) from multiexcitonic (MX) complexes in
      nanocrystal quantum dots (NQDs) has been severely restricted due to efficient
      nonradiative Auger recombination leading to very low MX emission quantum yields.
      Here we employed "giant" CdSe/CdS NQDs with suppressed Auger recombination to
      study ET of biexcitons (BX) and charged excitons (trions) into Si substrate.
      Photoluminescence (PL) measurements of (sub)monolayers of gNQDs controllably
      assembled on various interacting surfaces and augmented by single gNQD's imaging
      reveal appearance of BX spectral signatures and progressive acceleration of PL
      lifetimes of all excitonic species on Si substrates. From statistical analysis of
      a large number of PL lifetime traces, representative exciton, trion and BX ET
      efficiencies are measured as ~75%, 55% and 45% respectively. Detailed analysis of
      the MX's radiative rates demonstrate the crucial role of the radiative
      (waveguide) ET in maintaining high overall transfer efficiency despite the
      prevalent Auger recombination. Our observations point towards practical
      utilization of MX-bearing nanocrystals in future optoelectronics architectures.

PMID- 29210417
TI  - Reactive oxygen species (ROS)-responsive nanomedicine for RNAi-based cancer
      therapy.
AB  - Although much effort has been dedicated to the development of efficient siRNA
      delivery for cancer therapy, delivery nanomaterials that can particularly respond
      to reactive oxygen species (ROS), which are overproduced in the tissue and
      mitochondria of cancer cells, are still rare for the clinical translation of RNA
      interference (RNAi)-based therapy. To this end, we developed a ROS-responsive
      boronic vehicle with a lipid envelope for systemic vascular endothelial growth
      factor (VEGF) siRNA delivery so as to improve RNAi cancer therapy. We found that
      the efficiency of siRNA delivery largely relied on the ROS responsiveness of the
      carrier we have developed to mediate timely siRNA release, the PEG-functionalized
      lipid layer to shield the surface charge of polyplexes as well as the ability of
      the phenylboronic moiety to stabilize siRNA. The unique carrier nanostructure
      provides the efficient systemic transportation of siRNA to the tumor site for
      effective knockdown of the VEGF, which resulted in a significant antiangiogenesis
      effect and the effective inhibition of tumor growth in vivo. The current study
      defines a new systemic delivery strategy for siRNA by cooperatively integrating
      multifunctional lipid coatings with the ROS-responsive boronic polymer, which may
      potentially benefit RNAi-based therapy in the dawning era of precision
      nanomedicine for cancer therapy.

PMID- 29210418
TI  - Thiolated DNA-templated silver nanoclusters with strong fluorescence emission and
      a long shelf-life.
AB  - Thiolated DNA (DNA-SH) was employed as a template in the synthesis and
      stabilization of AgNCs (DNA-SH-AgNCs). Resulting from the synergistic protective
      effect of specific Ag+-DNA interactions and Ag-S bonding, DNA-SH-AgNCs exhibited
      high quantum yields and resistance to oxidation.

PMID- 29210419
TI  - Polyethylene nano crystalsomes formed at a curved liquid/liquid interface.
AB  - Crystallization is incommensurate with nanoscale curved space due to the lack of
      three dimensional translational symmetry of the latter. Herein, we report the
      formation of single-crystal-like, nanosized polyethylene (PE) capsules using a
      miniemulsion solution crystallization method. The miniemulsion was formed at
      elevated temperatures using PE organic solution as the oil phase and sodium
      dodecyl sulfate as the surfactant. Subsequently, cooling the system stepwisely
      for controlled crystallization led to the formation of hollow, nanosized PE
      crystalline capsules, which are named as crystalsomes since they mimic the
      classical self-assembled structures such as liposome, polymersome and
      colloidosome. We show that the formation of the nanosized PE crystalsomes is
      driven by controlled crystallization at the curved liquid/liquid interface of the
      miniemulson droplet. The morphology, structure and mechanical properties of the
      PE crystalsomes were characterized using scanning electron microscopy,
      transmission electron microscopy, X-ray diffraction, and atomic force
      spectroscopy. Electron diffraction showed the single-crystal-like nature of the
      crystalsomes. The incommensurateness between the nanocurved interface and the
      crystalline packing led to reduced crystallinity and crystallite size of the PE
      crystalsome, as observed from the X-ray diffraction measurements. Moreover,
      directly quenching the emulsion below the spinodal line led to the formation of
      hierarchical porous PE crystalsomes due to the coupling of the PE crystallization
      and liquid/liquid phase separation. We anticipate that this unique crystalsome
      represents a new type of nanostructure that might be used as nanodrug carriers
      and ultrasound contrast agents.

PMID- 29210420
TI  - A novel approach to 5H-pyrazino[2,3-b]indoles via annulation of 3-diazoindolin-2
      imines with 2H-azirines or 5-alkoxyisoxazoles under Rh(ii) catalysis.
AB  - A novel one-step method for the preparation of 5H-pyrazino[2,3-b]indoles with
      different substitution patterns in all rings of the tricyclic system via the
      Rh2(OAc)4-catalyzed reaction of 2H-azirines with 3-diazoindolin-2-imines is
      reported. Alkyl 5H-pyrazino[2,3-b]indole-3-carboxylates were also prepared by a
      one-pot procedure from synthetic equivalents of alkyl 2H-azirine-2-carboxylates,
      5-alkoxyisoxazoles. The reactions provide the first examples of the use of Rh(ii)
      catalysis for intermolecular annulations with 2H-azirines and isoxazoles.

PMID- 29210422
TI  - A two-dimensional tetragonal yttrium nitride monolayer: a ferroelastic
      semiconductor with switchable anisotropic properties.
AB  - We propose a two-dimensional (2D) tetragonal material: an yttrium nitride (t-YN)
      monolayer, with a distinguished combination of mechanical and electronic
      properties based on first-principles calculations. We find that the t-YN
      monolayer is a low direct band gap semiconductor (0.55 eV) with strong
      anisotropic mechanical and electronic properties. We also identify that the t-YN
      monolayer to be a 2D ferroelastic material with a reversible strain of about
      14.4%, indicating that the anisotropic properties of the t-YN monolayer can be
      switched by applying external stress. Furthermore, the moderate-switching barrier
      (33 meV/atom) of ferroelastic lattice rotation renders the switchable anisotropic
      properties accessible experimentally. These outstanding properties make the t-YN
      monolayer a promising switchable anisotropic 2D material for electronic and
      mechanical applications.

PMID- 29210421
TI  - Cyclic azole-homologated peptides from Marine sponges.
AB  - This review discusses the chemistry of cyclic azole-homologated peptides (AHPs)
      from the marine sponges, Theonella swinhoei, other Theonella species, Calyx spp.
      and Plakina jamaicensis. The origin, distribution of AHPs and molecular structure
      elucidations of AHPs are described followed by their biosynthesis, bioactivity,
      and synthetic efforts towards their total synthesis. Reports of partial and total
      synthesis of AHPs extend beyond peptide coupling reactions and include creative
      construction of the non-proteinogenic amino acid components, mainly the
      homologated heteroaromatic and alpha-keto-beta-amino acids. A useful conclusion
      is drawn regarding AHPs: despite their rarity, exotic structures and the potent
      protease inhibitory properties of some members, their synthesis is under
      developed and beckons solutions for outstanding problems towards their efficient
      assembly.

PMID- 29210423
TI  - Bimodal phase separated block copolymer/homopolymer blends self-assembly for
      hierarchical porous metal nanomesh electrodes.
AB  - Transparent conducting electrodes (TCEs) are essential components in various
      optoelectronic devices. Nanostructured metallic thin film is one of the promising
      candidates to complement current metal oxide films, such as ITO, where high cost
      rare earth elements have been a longstanding issue. Herein, we present that
      multiscale porous metal nanomesh thin films prepared by bimodal self-assembly of
      block copolymer (BCP)/homopolymer blends may offer a new opportunity for TCE.
      This hierarchical concurrent self-assembly consists of macrophase separation
      between BCP and homopolymer as well as microphase separation of BCP, and thus
      provides a straightforward spontaneous production of a highly porous multiscale
      pattern over an arbitrary large area. Employing a conventional pattern transfer
      process, we successfully demonstrated a multiscale highly porous metallic thin
      film with reasonable optical transparency, electro-conductance, and large-area
      uniformity, taking advantage of low loss light penetration through microscale
      pores and significant suppression of light reflection at the nanoporous
      structures. This well-defined controllable bimodal self-assembly can offer
      valuable opportunities for many different applications, including
      optoelectronics, energy harvesting, and membranes.

PMID- 29210424
TI  - Cyclic olefin copolymer as an X-ray compatible material for microfluidic devices.
AB  - The combination of microfluidics and X-ray methods attracts a lot of attention
      from researchers as it brings together the high controllability of microfluidic
      sample environments and the small length scales probed by X-rays. In particular,
      the fields of biophysics and biology have benefited enormously from such
      approaches. We introduce a straightforward fabrication method for X-ray
      compatible microfluidic devices made solely from cyclic olefin copolymers. We
      benchmark the performance of the devices against other devices including more
      commonly used Kapton windows and obtain data of equal quality using small angle X
      ray scattering. An advantage of the devices presented here is that no gluing
      between interfaces is necessary, rendering the production very reliable. As a
      biophysical application, we investigate the early time points of the assembly of
      vimentin intermediate filament proteins into higher-order structures. This weakly
      scattering protein system leads to high quality data in the new devices, thus
      opening up the way for numerous future applications.

PMID- 29210425
TI  - In situ synthesis of iron sulfide embedded porous carbon hollow spheres for
      sodium ion batteries.
AB  - Iron sulfide embedded porous carbon hollow spheres (FeSx@CS) have been
      successfully synthesized through a facile and environment friendly in situ
      synthetic method. Using this method, a porous carbon matrix and uniformly
      dispersed iron sulfide nanoparticles were formed simultaneously and assembled
      into hollow spheres. The as-synthesized FeSx@CS material showed high reversible
      capacity, outstanding cycle performance, and excellent rate capability when it
      was applied as an anode material for sodium ion batteries. It delivered a
      remarkable charge capacity of 656.75 mA h g-1 in the first cycle and a capacity
      retention of 97% after 100 cycles. When the current density was increased from 50
      mA g-1 to 1000 and 2000 mA g-1, high capacity retention of 76.3% and 62.5% was
      achieved, respectively.

PMID- 29210426
TI  - Probing nano-patterned peptide self-organisation at the aqueous graphene
      interface.
AB  - The peptide sequence GrBP5, IMVTESSDYSSY, is found experimentally to bind to
      graphene, and ex situ atomic force microscopy indicates the formation of an
      ordered over-layer on graphite. However, under aqueous conditions neither the
      molecular conformations of the adsorbed peptide chains, nor the molecular-level
      spatial ordering of the over-layer, has been directly resolved. Here, we use
      advanced molecular dynamics simulations of GrBP5, and related mutant sequences,
      to elucidate the adsorbed structures of both the peptide and the adsorbed peptide
      over-layer at the aqueous graphene interface. In agreement with a previous
      hypothesis, we find GrBP5 binds at the aqueous graphene interface chiefly via the
      tyrosine-rich C-terminal region. Our simulations of the adsorbed peptide over
      layers reveal that the peptide chains form an aggregate that does not evolve
      further into ordered patterns. Instead, we find that the inter-chain interactions
      are driven by hydrogen bonding and charge-charge interactions that are not
      sufficiently specific to support pattern formation. Overall, we suggest that the
      experimentally-observed over-layer pattern may be due to the drying of the
      sample, and may not be prevalent at the solvated interface. However, our
      simulations indicate sequence modifications of GrBP5 to promote over-layer
      ordering under aqueous conditions.

PMID- 29210427
TI  - Controllable manipulation of bubbles in water by using underwater superaerophobic
      graphene-oxide/gold-nanoparticle composite surfaces.
AB  - Manipulation of bubbles in water is of great importance in the mineral industry,
      oil production and separation, wastewater treatments, boiling processes,
      biological cell incubations, microfluidics and miniature reactor technologies.
      Generally, bubbles in an aqueous environment are inclined to stick to the channel
      walls, resulting in blockage and energy-consuming treatments. Herein, we report
      the fabrication of low-adhesion graphene-oxide (GO)/gold-nanoparticle (GNP)
      hybrid films with a good underwater superaerophobicity, which have the ability to
      arbitrarily manipulate bubbles in water. Owing to the hydrophilic nature of GO
      nanosheets and hierarchical structures of aggregated GNPs, the GO/GNP hybrid
      films showed low adhesion towards bubbles in water. Thus, bubbles could be freely
      manipulated using home-made tools coated with these low-adhesion, underwater
      superaerophobic GO/GNP hybrid films. The controlled 1D and 2D movements of one
      bubble and merging/reaction of two bubbles can be achieved. This study provides a
      new avenue to design new strategies for bubble manipulations, and further extends
      the application of superwettable 2D materials in interface fields involving gas
      phases.

PMID- 29210428
TI  - Lectin-gated and glycan functionalized mesoporous silica nanocontainers for
      targeting cancer cells overexpressing Lewis X antigen.
AB  - Gated mesoporous silica nanoparticles can deliver payload upon the application of
      a predefined stimulus, and therefore are promising drug delivery systems. Despite
      their important role, relatively low emphasis has been placed on the design of
      gating systems that actively target carbohydrate tumor cell membrane receptors.
      We describe herein a new Lewis X (Lex) antigen-targeted delivery system
      comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye,
      functionalized with a Lex derivative (1) and capped with a fucose-specific
      carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes
      advantage of the affinity of AAL for Lex overexpressed receptors in certain
      cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind
      Lex, and selectins in the cells bind Lex in the gated MSNs, thereby inducing
      cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO
      430LS dye delivered correlated with the amount of Lex antigen overexpressed at
      the DLD-1 cell surface. This is one of the few examples of MSNs using
      biologically relevant glycans for both capping (via interaction with AAL) and
      targeting (via interaction with overexpressed Lex at the cell membrane).

PMID- 29210429
TI  - Probing magnetic coupling between LnPc2 (Ln = Tb, Er) molecules and the
      graphene/Ni (111) substrate with and without Au-intercalation: role of the
      dipolar field.
AB  - Lanthanides (Ln) bis-phthalocyanine (Pc), the so-called LnPc2double decker, are a
      promising class of molecules with a well-defined magnetic anisotropy. In this
      work, we investigate the magnetic properties of LnPc2 molecules UHV-deposited on
      a graphene/Ni(111) substrate and how they modify when an Au layer is intercalated
      between Ni and graphene. X-ray absorption spectroscopy (XAS), and linear and
      magnetic circular dichroism (XLD and XMCD) were used to characterize the systems
      and probe the magnetic coupling between LnPc2 molecules and the Ni substrate
      through graphene, both gold-intercalated and not. Two types of LnPc2 molecules
      (Ln = Tb, Er) with a different magnetic anisotropy (easy-axis for Tb, easy-plane
      for Er) were considered. XMCD shows an antiferromagnetic coupling between Ln and
      Ni(111) even in the presence of the graphene interlayer. Au intercalation causes
      the vanishing of the interaction between Tb and Ni(111). In contrast, in the case
      of ErPc2, we found that the gold intercalation does not perturb the magnetic
      coupling. These results, combined with the magnetic anisotropy of the systems,
      suggest the possible importance of the magnetic dipolar field contribution for
      determining the magnetic behaviour.

PMID- 29210431
TI  - Scandium as a pre-catalyst for the deoxygenative allylation of benzylic alcohols.
AB  - Scandium triflate is an effective pre-catalyst for the deoxygenative allylation
      of benzylic alcohols with a narrow substrate window. The reaction is shown to
      proceed through a "hidden Bronsted acid" mechanism. The reaction is efficient
      provided that the aryl group is neither too electron rich nor too electron poor.
      It is shown that this allows useful selectivity. The reaction also works for
      benzyhydryl alcohols with broader scope. The reaction may also be catalysed by
      Nafion.

PMID- 29210434
TI  - Nano-confinement-driven enhanced magnetic relaxivity of SPIONs for targeted tumor
      bioimaging.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are highly biocompatible and
      have a versatile synthetic technique based on coprecipitation, reduction
      precipitation, and hydrothermal methods, where Fe3+ and Fe2+ react in aqueous
      solutions; both these ions are present in our body and have clear metabolic
      pathways; therefore, they have attracted extensive research interest and
      development in the field of diagnostic imaging and therapy. However, most SPION
      based clinical diagnostic contrast agents are discontinued due to severe pain,
      low transverse magnetic relaxivity range of 80-180 mM-1 s-1, shorter circulation
      half-life, and lack of disease specificity. Therefore, in this study, we
      engineered a bone cancer-targeted hybrid nanoconstruct (HNC) with a high
      transverse magnetic relaxivity of 625 mM-1 s-1, which was significantly higher
      than that of clinical contrast agents. The engineered HNC is peripherally
      decorated with a bone-seeking agent, alendronic acid-conjugated phospholipid,
      exhibiting a hydrodynamic size of 80 nm with a negative surface potential, -35
      mV. The interior skeleton of the HNC is composed of biodegradable and
      biocompatible poly(l-lactic-co-glycolic acid) (PLGA), in which 5 nm SPIONs are
      confined. We have successfully tuned the distance between the confined SPIONs
      from 0.5 to 4 nm, as revealed by transmission electron microscopy (TEM) images
      and magnetic resonance image (MRI) phantoms. This cluster confinement
      dramatically enhances magnetic relaxivity possibly due to the increase in net
      local magnetization due to proximal field inhomogeneity. In an in vitro
      examination, 80% of HNC is found to bind with hydroxyapatite (HAp), which when
      characterized by TEM shows a painting of SPIONs over a HAp crystal. HNC is found
      to accumulate in mouse osteosarcoma tumor (K7M2 tumor model); both MRI and
      histological examination of the tumor show the potential of HNC as targeting
      agents for diagnosis of tumor in the bone.

PMID- 29210435
TI  - Left- and right-circularly polarized light-sensing based on colored and mechano
      responsive chiral nematic liquid crystals.
AB  - A liquid crystal host-guest system composed of achiral organic molecules (host)
      and colored chiral metal complexes (guest) was fabricated to sense both right-
      and left-handed circularly polarized light (r- and l-CPL), depending on the guest
      (dopant) concentration. The CPL-sensing can be reversibly turned on and off upon
      mechanical stress and heating.

PMID- 29210437
TI  - Size controllable DNA nanogels from the self-assembly of DNA nanostructures
      through multivalent host-guest interactions.
AB  - Nanogels made of biomolecules are one of the potential candidates as a
      nanocarrier for drug delivery applications. The unique structural characteristics
      and excellent biocompatibility of DNA suggest that DNA nanogels would be an ideal
      candidate. Herein, a general design strategy for the crafting of DNA nanogels
      with controllable size using the multivalent host-guest interaction between beta
      CD functionalized branched DNA nanostructures as the host and a star-shaped
      adamantyl-terminated 8-arm poly(ethylene glycol) polymer as the guest is
      reported. Our results reveal that multivalent host-guest interactions are
      necessary for the nanogel formation. Nanogels exhibit excellent biocompatibility,
      good cell permeability and high drug encapsulation ability, which are promising
      features for their application as a drug carrier. The encapsulation of
      doxorubicin, an anticancer drug, inside the hydrophobic network of the nanogel
      and its delivery into cancer cells are also reported. We hope that the general
      design strategy demonstrated for the creation of DNA nanogels may encourage other
      researchers to use this approach for the design of DNA nanogels of other DNA
      nanostructures, and explore the potential of DNA nanogels in drug delivery
      applications.

PMID- 29210438
TI  - In-plane molecular organization of hydrated single lipid bilayers:
      DPPC:cholesterol.
AB  - Understanding the physical properties of cholesterol-phospholipid systems is
      essential to gain a better knowledge of the function of each membrane
      constituent. We present a novel, simple and user-friendly setup that allows for
      the straightforward grazing incidence X-ray diffraction characterization of
      hydrated individual supported lipid bilayers. This configuration minimizes the
      scattering from the liquid and allows the detection of the extremely weak
      diffracted signal of the membrane, enabling the differentiation of the coexisting
      domains in DPPC:cholesterol single bilayers.

PMID- 29210439
TI  - Translationally invariant colloidal crystal templates.
AB  - We show that dynamic, feed-back controlled optical traps, whose positions depend
      on the instantaneous local configuration of particles in a pre-determined way,
      can stabilise colloidal particles in finite lattices of any given symmetry.
      Unlike in a static template, the crystal so formed is invariant under uniform
      translations and retains all possible zero energy modes. We demonstrate this in
      silico by stabilising the unstable two-dimensional square lattice in a model soft
      solid with isotropic interactions.

PMID- 29210440
TI  - Microwave-annealing-induced nanowetting of block copolymers in cylindrical
      nanopores.
AB  - Block copolymers have attracted great attention because of their abilities to
      self-assemble into well-ordered microphase-separated structures. To generate
      nanopatterns of block copolymers with long-range ordering and low-defect
      densities in shorter time scales, microwave annealing has recently been applied.
      Microwave annealing, however, has so far only been used for block copolymer bulks
      and thin films. In this work, we discover that microwave annealing can be
      successfully applied to three-dimensional block copolymer nanostructures by
      studying the infiltration and microphase separation of block copolymers in
      cylindrical nanopores upon microwave irradiation. Cylinder-forming and lamella
      forming poly(styrene-block-dimethylsiloxane) (PS-b-PDMS) are introduced into the
      nanopores of anodic aluminum oxide (AAO) templates. In addition, AAO templates
      with different pore sizes are used to study the effect of the commensurabilities
      between the pore diameters and the repeating periods of the block copolymers on
      the morphologies of the block copolymer nanostructures.

PMID- 29210441
TI  - Barriers for Prevention and Prodromal AD Trials.

PMID- 29210442
TI  - Registries and Cohorts to Accelerate Early Phase Alzheimer's Trials. A Report
      from the E.U./U.S. Clinical Trials in Alzheimer's Disease Task Force.
AB  - The EU/US/CTAD Task Force, an international collaboration of AD investigators
      from industry and academia, met in Barcelona, Spain, on November 4th, 2015, to
      explore existing and planned patient registries and other clinical trial
      infrastructure meant to expedite recruitment of large numbers of participants
      into clinical trials and improve their productivity. The Task Force identified a
      number of approaches currently being tested around the world, including the use
      of predictive algorithms to identify individuals likely to have prodromal or
      preclinical AD, the establishment of clinical trial networks to streamline
      trials, and reforming the informed consent process to make it less burdensome to
      both investigators and trial participants. Multi-national systems such as the
      European Prevention of Alzheimer's Dementia (EPAD) and the Global Alzheimer's
      Platform (GAP) offer value for sponsors, trial sites, and patients by optimizing
      efforts to find effective disease-modifying and symptomatic treatments.

PMID- 29210443
TI  - Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Individuals with Early
      Alzheimer's Disease: Amyloid Imaging Positron Emission Tomography and Safety
      Results from a Phase 2 Study.
AB  - BACKGROUND: ACC-001 is an investigational therapeutic vaccine designed to elicit
      antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide,
      believed to be important in the pathogenesis of Alzheimer's disease. OBJECTIVES:
      To evaluate safety, immunogenicity, impact on brain amyloid, and other
      exploratory endpoints in participants receiving ACC-001. DESIGN: Randomized,
      phase 2, interventional study. TRIAL REGISTRATION: Clinicaltrials.gov ID
      NCT01227564. PARTICIPANTS: Individuals with early Alzheimer's disease (Mini
      Mental State Examination scores >=25, a global Clinical Dementia Rating of 0.5,
      and evidence of elevated baseline brain amyloid burden). INTERVENTION:
      Participants were randomized to ACC-001 3 ug or 10 ug with QS-21 adjuvant (50
      ug), or placebo. MEASUREMENTS: The primary endpoint was change in brain amyloid
      burden by 18F-florbetapir positron emission tomography in composite cortical
      standard uptake value ratio. RESULTS: A total of 63 participants were randomized
      and 51 completed the study. At week 104, no significant differences were observed
      in 18F-florbetapir positron emission tomography composite cortical standard
      uptake value ratio between either ACC-001 dose compared with placebo. In both ACC
      001 + QS-21 treatment groups, following the initial immunization, the anti
      amyloid-beta geometric mean titers increased after each subsequent vaccination
      and then declined, with less apparent decline after the later compared with
      earlier immunizations. The majority of treatment-emergent adverse events in the
      ACC-001 + QS-21 groups were injection site reactions, which occurred at a greater
      rate in active treatment groups than in the placebo group. No amyloid-related
      imaging abnormalities of edema or effusion were reported. CONCLUSION: No
      statistically significant differences were observed between groups in the change
      from baseline brain amyloid burden despite apparently robust systemically
      measured anti-amyloid-beta antibody response at both dose levels. Insufficient
      antibody titers, poor quality immune response, short duration of treatment, or
      small sample size may have resulted in these findings. The safety and
      tolerability profile was acceptable.

PMID- 29210444
TI  - Longitudinal Trajectories of Clinical Decline in Amyloid Positive and Negative
      Populations.
AB  - BACKGROUND: Brain beta-amyloid status portends different trajectories of clinical
      decline. OBJECTIVE: Determine trajectories and predictive baseline variable(s).
      DESIGN: Longitudinal, up to 24 months. SETTING: ADNI sites. PARTICIPANTS: Healthy
      control (n=325), early and late mild cognitive impairment (n=279; n=372), and
      Alzheimer's dementia (n=216) subjects from ADNI-1/GO/2. MEASUREMENTS: Baseline
      amyloid status was based on first available CSF Abeta1-42 or, [11C]PiB or
      [18F]florbetapir (FBP) PET. Alzheimer's Disease Assessment Scale-Cognitive
      Subscale (ADAS-Cog13) and Functional Activities Questionnaire (FAQ) were co
      analyzed using Growth Mixture Modeling (GMM) to define latent class trajectories
      for each amyloid group. Classification and Regression Tree (CART) analysis
      determined which variables best predicted trajectory class membership using a
      number of variables available to clinicians. RESULTS: GMMs found two trajectory
      classes (C1, C2) each for amyloid-positive (P; n=722) and negative (N; n=470)
      groups. Most (90%) in the negative group were C2N with mildly impaired baseline
      ADAS-Cog13, normal FAQ and nonprogression; 10% were C1N with moderately impaired
      baseline FAQ and ADAS-Cog13 and trajectory of moderately worsening scores on the
      FAQ. C1P (26%) had more impaired baseline FAQ and ADAS-Cog13 than C2P (74%) and a
      steeper declining trajectory. CART yielded 4 decision nodes (FAQ <10.5, FAQ <6.5,
      MMSE >=26.5, age <75.5) in positive and 1 node (FAQ <6.5) in negative groups,
      with 91.4% and 92.8% accuracy for class assignments, respectively. CONCLUSIONS:
      The trajectory pattern of greater decline in amyloid positive subjects was
      predicted by greater baseline impairment of cognition and function. While most
      amyloid-negative subjects had nonprogression irrespective of their diagnosis, a
      subgroup declined similarly to the gradually declining amyloid-positive group.
      CART predicted likely trajectory class, with known amyloid status, using
      variables accessible in a clinical setting, but needs replication.

PMID- 29210445
TI  - A Novel Eigenvector-based Method to Detect Mild Alzheimer's Disease Using Event
      Related Potentials.
AB  - Event-related potentials (ERPs) are a physiological measure of cognitive function
      that have shown diagnostic and prognostic utility in Alzheimer's disease (AD). In
      this study, we used a novel eigenvector-based technique to better understand
      brain electrophysiological differences between subjects with mild AD and healthy
      controls (HC). Using ERPs from 75 subjects with mild AD and 95 HC, we first
      calculated cognitive task eigenvectors within each subject from three conditions
      and then calculated second-order eigenvector components to compare the AD group
      to the HC group. A MANOVA of the three second-level components discriminated
      between AD and HC multivariately (Wilks' lambda=.4297, p<0.0001, R2 = .5703), and
      also on each of the three components univariately (all 3 p-values<0.0001). The
      eigenvector-based technique used in this study accurately discriminated between
      the mild AD group and HC. As such, this analysis method adds to our understanding
      of the differences in ERP signal between AD and HC, and could provide a sensitive
      biomarker for diagnosis and monitoring of AD progression.

PMID- 29210446
TI  - Quantification of noninvasive fat reduction: A systematic review.
AB  - BACKGROUND AND OBJECTIVE: Noninvasive fat reduction appears effective, but there
      are various methods for quantifying changes. The objective of this review is to
      assess comparative utility measures of subcutaneous fat. STUDY DESIGN/MATERIALS
      AND METHODS: Articles describing noninvasive fat reduction were searched using
      MEDLINE, EMBASE, CINAHL and Scopus electronic databases on two dates (January 28,
      2014 and February 16, 2016). Titles of studies and abstracts were screened for
      eligibility. Manual review was performed by two investigators to detect those
      that: (1) included original data; (2) were randomized controlled trials, or
      prospective or retrospective cohort studies; (3) quantified fat outcomes; and (4)
      enrolled at least 10 subjects. RESULTS: Of 1,057 retrieved articles, 36 met
      criteria. Most reported four or more measurement techniques. Circumference
      measurements were most commonly cited. Other objective techniques, like caliper
      thickness, ultrasound, magnetic resonance imaging (MRI), and three-dimensional
      (3D) photography, were also used. Common subjective methods were evaluation of
      standardized photographs by blinded raters and patient satisfaction surveys.
      CONCLUSIONS: For quantifying noninvasive fat reduction, all available methods had
      significant limitations: photographic comparisons were subjective; circumference
      or caliper measurements were confounded; ultrasound was operator dependent; MRI
      was expensive; computed models and simulations were in early development. As new
      technologies are developed, the need for reliable, accurate and practical
      measures of subcutaneous fat will increase. Lasers Surg. Med. 50:96-110, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29210447
TI  - Improvement of physico-chemical properties and phenolic compounds bioavailability
      by concentrating dietary fiber of peach (Prunus persica) juice by-product.
AB  - BACKGROUND: This study aimed to concentrate dietary fiber (DF) from peach (Prunus
      persica) juice by-product (PJBP), to improve its functional properties, and its
      polyphenols bioavailability. The dietary fiber concentrates (DFCs) were obtained
      from PJBP using water/ethanol treatments (100:0, 20:80, 50:50, 80:20, and 0:100,
      v/v) at 1:5 ratio (wet weight/solvent, w/v) for 5 and 20 min at 21  degrees C.
      RESULTS: All treatments concentrated condensed tannins, total and insoluble DF,
      with the highest content found with 100% H2 O treatment. The major polyphenols of
      DFC were 4-O-caffeoylquinic, chlorogenic, and 1,5-di-O-caffeoylquinic acids.
      Water and oil retention capacity and maximum glucose diffusion rate were improved
      mainly with 100% H2 O treatment. Healthy rats were fed with a standard diet
      supplemented with 8% of PJBP, DFC obtained with 100% H2 O for 5 min, or DFC
      obtained with 20% EtOH for 5 min. Gastrointestinal digesta weight and viscosity
      were increased in animals supplemented with 100% H2 O DFC. Moreover, the urinary
      excretion of polyphenol metabolites, mainly glucuronide and sulfate conjugates,
      was increased with this treatment, indicating a greater bioavailability of PJBP
      polyphenols, which was associated with an increased dietary fiber porosity.
      CONCLUSION: Water treatment could be used to potentiate PJBP functional
      properties and polyphenols bioavailability. (c) 2017 Society of Chemical
      Industry.

PMID- 29210448
TI  - Maternal effects and parent-offspring conflict.
AB  - Maternal effects can provide offspring with reliable information about the
      environment they are likely to experience, but also offer scope for maternal
      manipulation of young when interests diverge between parents and offspring. To
      predict the impact of parent-offspring conflict, we model the evolution of
      maternal effects on local adaptation of young. We find that parent-offspring
      conflict strongly influences the stability of maternal effects; moreover, the
      nature of the disagreement between parents and young predicts how conflict is
      resolved: when mothers favor less extreme mixtures of phenotypes relative to
      offspring (i.e., when mothers stand to gain by hedging their bets), mothers win
      the conflict by providing offspring with limited amounts of information. When
      offspring favor overproduction of one and the same phenotype across all
      environments compared to mothers (e.g., when offspring favor a larger body size),
      neither side wins the conflict and signaling breaks down. Only when offspring
      favor less extreme mixtures relative to their mothers (something no current model
      predicts), offspring win the conflict and obtain full information about the
      environment. We conclude that a partial or complete breakdown of informative
      maternal effects will be the norm rather than the exception in the presence of
      parent-offspring conflict.

PMID- 29210449
TI  - Mixture Design Applied to the Development of Chickpea-Based Gluten-Free Bread
      with Attractive Technological, Sensory, and Nutritional Quality.
AB  - : The aim of the study was utilized chickpea to create appealing, nutritious, and
      palatable gluten-free bread (GFB). The performance of chickpea flour (CF) in
      single and composite GFB formulations was studied with a mixture design and
      response surface methodology. Six simplex-centroid designs for 3 ingredients were
      used to identify the ideal proportions of CF in various blends with cassava
      starch (CS), maize starch (MS), potato starch (PS), and rice flour (RF) achieving
      the best physical properties. For each design, 3 single, 3 binary, and 3 ternary
      formulations were prepared. The results showed that CF alone is suitable for
      bread production, resulting in GFB with higher volume and crumb firmness and
      lower crumb moisture than single formulations of other raw materials. However,
      the interactions between CF and PS or CS enhanced the loaf volume and decreased
      the crumb firmness values. The GFB prepared with only CF was accepted (overall
      acceptability score of 7.1- on a 10-cm scale). Nevertheless, the composite
      formulations prepared with CF75:PS25 or CF75:CS25 (flour basis) received overall
      acceptability scores of 8.2, like those of their white GFB, prepared with
      RF50:PS50 blend (flour basis), and wheat bread counterparts, used as positive
      controls. Compared to white GFB, both composite formulations presented nearly a
      twofold increase in ash and protein contents and a threefold increase in total
      fiber content. These results show that blends of CF75:PS25 or CF75:CS25 can be
      used to develop GFB with a good physical and sensory properties, as well as an
      enhanced nutritional composition. PRACTICAL APPLICATION: Gluten-free bread (GFB)
      made with 75% chickpea flour (CF) blend with 25% potato or cassava starch showed
      improved total minerals, protein and dietary fiber content and bread quality
      characteristics. Therefore, CF is a valuable ingredient for food technologists in
      manufacturing better-tasting and healthy GFB, which is important for consumers
      with gluten-related disorders since GFB often lack nutrition content, appearance,
      texture, and mouthfeel.

PMID- 29210450
TI  - Detection of allergen coding sequences of kiwi, peach, and apple in processed
      food by qPCR.
AB  - BACKGROUND: Food traceability becomes lifesaving for persons suffering severe
      allergy or intolerance, and therefore need a complete avoidance of the immune
      trigger food. This paper describes how to fingerprint the presence of some
      allergenic species (kiwi, peach, and apple) in foods by quantitative real-time
      PCR (qPCR). RESULTS: Five DNA extraction procedures were tested on fruits and
      foods. The results were statistically evaluated, and discussed. Analysis by qPCR
      with SYBR Green was developed to detect traces of these allergenic species in
      foods. Plasmids containing the target sequences of kiwi, peach and apple were
      employed as internal reference standard. Analysis of spiked food samples showed a
      limit of detection of 25 mg kg-1 for kiwi, 20 mg kg-1 for peach and 50 mg kg-1
      for apple. CONCLUSION: The qPCR method here developed, combined with the use of
      internal plasmid reference standard, represents a specific system for the quick
      detection of allergenic species in complex food matrices, with a limit of
      detection comparable with those reported using more time-consuming methods. (c)
      2017 Society of Chemical Industry.

PMID- 29210451
TI  - Inactivation Methods of Trypsin Inhibitor in Legumes: A Review.
AB  - Seed legumes have played a major role as a crop worldwide, being cultivated on
      about 12% to 15% of Earth's arable land; nevertheless, their use is limited by,
      among other things, the presence of several antinutritional factors (ANFs -
      naturally occurring metabolites that the plant produces to protect itself from
      pest attacks.) Trypsin inhibitors (TIs) are one of the most relevant ANFs because
      they reduce digestion and absorption of dietary proteins. Several methods have
      been developed in order to inactivate TIs, and of these, thermal treatments are
      the most commonly used. They cause loss of nutrients, affect functional
      properties, and require high amounts of energy. Given the above, new processes
      have emerged to improve the nutritional quality of legumes while trying to solve
      the problems caused by the use of thermal treatments. This review examines and
      discusses the methods developed by researchers to inactivate TI present in
      legumes and their effects over nutritional and functional properties.

PMID- 29210452
TI  - Does thalidomide prolong survival in dogs with splenic haemangiosarcoma?
AB  - OBJECTIVES: To investigate thalidomide as an adjuvant treatment for canine
      haemangiosarcoma. MATERIALS AND METHODS: Fifteen dogs with splenic
      haemangiosarcoma, initially treated by splenectomy, were included. Following
      recovery from surgery, all dogs received thalidomide continuously until their
      death. Tumour stage was established using CT scans of the chest and abdomen
      immediately before starting thalidomide treatment and again three months later.
      Cause of death was confirmed by post mortem examination. RESULTS: The median
      survival time of dogs receiving thalidomide was 172 days (95% confidence
      interval: 93 to 250 days). Five dogs (33% of the population receiving
      thalidomide) survived more than 1 year (range 458 to 660 days) after surgery.
      Dogs with stage 2 disease that received thalidomide also had a longer survival
      time than dogs with stage 3 disease (median survival time 303 versus 40 days). Of
      15 dogs, 13 died from metastatic haemangiosarcoma. CLINICAL SIGNIFICANCE:
      Treatment using thalidomide may improve survival of dogs with splenic
      haemangiosarcoma and should be considered a possible adjuvant therapy.

PMID- 29210453
TI  - A Combined Approach of Infrared Spectroscopy and Multivariate Analysis for the
      Simultaneous Determination of Sugars and Fructans in Strawberry Juices During
      Storage.
AB  - : In this work, a Fourier transform mid-infrared spectroscopy (FTIR)-based method
      was developed for simultaneously quantifying simple sugars and exogenously added
      fructooligosaccharides (FOS) in strawberry juices preserved for up to 14 d using
      nonthermal techniques (geraniol and vanillin+ultrasound). The main spectral
      differences were observed in the 1200 to 900 cm-1 region. The presence of FOS was
      identified by the typical bands at 1134, 1034, and 935 cm-1 . During storage, a
      significant decrease of sucrose was concomitant to an increase of glucose and
      fructose in juices stored without any previous preservation treatment, as
      determined by high-performance liquid chromatography (HPLC). A principal
      component analysis was performed on the FTIR spectra corresponding to the
      different treatments. The groups observed explained more than 94% of the variance
      and were related to changes in the carbohydrate composition during storage. Then,
      different partial least square models (PLS) were defined to determine the
      concentrations of glucose, sucrose, fructose, and those of exogenously added FOS
      with degrees of polymerization within 3 and 5. The carbohydrates' concentrations
      determined by HPLC were used as reference method. The models were validated with
      independent sets of data. The mean of predicted values fitted nicely those
      obtained by HPLC (correlation and R2  > 0.97), thus supporting the use of the PLS
      models to monitor the quality of strawberry juices in unknown samples. In
      conclusion, FTIR spectroscopy appears as an adequate analytical tool to quick
      assess whether juice formulations meet specifications in terms of authenticity,
      contamination and/or deterioration. PRACTICAL APPLICATION: FTIR spectroscopy
      provided a method potentially transferable to the food industry when associated
      with the multivariate analysis. The robust 21 PLS models defined in this work
      provided reliable tools for the rapid monitoring of juices' authenticity and/or
      deterioration. In this regard, FTIR associated to multivariate analysis enabled
      the determination of different sugars in a single measurement without the need of
      pure sugars as standards. This experimental simplicity supports the use of FTIR
      at the production line, and also contributes to save time in determining
      carbohydrates' composition and stability, in an environmentally friendly way.

PMID- 29210454
TI  - The functional roles of retromer in Parkinson's disease.
AB  - The endosomal system is critical for the maintenance of intracellular
      homeostasis, and defects in this system are often linked to neurological
      disorders. The retromer complex is a critical coordinator of endosomal dynamics
      and has functional roles in multiple cellular processes through sorting cargoes
      from endosomes to the trans-Golgi network (TGN) or to the plasma membrane.
      Mammalian retromer comprises a core Vps26-Vps35-Vps29 trimer and associates with
      a range of proteins to generate endosomal tubular-vesicular carriers. Alterations
      in retromer function or its molecular organization have been a rising risk factor
      for Parkinson's disease (PD). Although genetic evidence has shown several
      variants within retromer in late-onset PD cases, the exact molecular machineries
      by which retromer variants induce the development of PD are still not completely
      elucidated. In this Review, we will focus on the functional roles of retromer in
      neuronal health, summarize advances in defining the cellular pathological
      phenotype caused by retromer deficiency or PD-linked retromer variants and
      discuss the potential clues of how retromer deregulation may contribute to PD
      pathogenesis.

PMID- 29210455
TI  - Examining Differentiation of Self as a Mediator in the Biobehavioral Family
      Model.
AB  - The Biobehavioral Family Model (BBFM) is a biopsychosocial model of health. This
      model proposes that biobehavioral reactivity mediates the association between the
      family emotional climate and disease activity. To improve the clinical relevance
      of the BBFM, variables that mediate the association between family emotional
      climate and biobehavioral reactivity need to be tested. This study examined
      differentiation of self as a mediator. Using data from the Midlife Development in
      the United States study (n = 854), results suggested that differentiation of self
      mediated the association between the family and intimate partner emotional
      climate and mental health symptoms. These findings suggest that including
      differentiation of self into the BBFM may help interventions based on the model
      target factors that could improve health outcomes.

PMID- 29210456
TI  - Using carboxylated cellulose nanofibers to enhance mechanical and barrier
      properties of collagen fiber film by electrostatic interaction.
AB  - BACKGROUND: Collagen-based films including casings with a promising application
      in meat industry are still needed to improve its inferior performance. In the
      present study, the reinforcement of carboxylated cellulose nanofibers (CNF) for
      collagen film, based on inter-/intra- molecular electrostatic interaction between
      cationic acid-swollen collagen fiber and anionic carboxylated CNF, was
      investigated. RESULTS: Adding CNF decreased the zeta-potential but increased
      particle size of collagen fiber suspension, with little effect on pH.
      Furthermore, CNF addition led to a higher tensile strength but a lower
      elongation, and the water vapor and oxygen barrier properties were improved
      remarkably. Because the CNF content was 50 g kg-1 or lower, the films had a
      homogeneous interwoven network, and CNF homogeneously embedded into collagen
      fiber matrix according to the scanning electron microscopy and atomic force
      microscopy analysis. Additionally, CNF addition increased film thickness and
      opacity, as well as swelling rate. CONCLUSION: The incorporation of CNF endows
      collagen fiber films good mechanical and barrier properties over a proper
      concentration range (<= 50 g kg-1 collagen fiber), which is closely associated
      with electrostatic reaction of collagen fiber and CNF and, subsequently, the form
      of the homogenous, compatible spatial network, indicating a potential
      applications of CNF in collagenous protein films, such as edible casings. (c)
      2017 Society of Chemical Industry.

PMID- 29210457
TI  - Advances on the impact of thermal processing on structure and antigenicity of
      chicken ovomucoid.
AB  - BACKGROUND: Ovomucoid (OVM) is the dominant allergen found in egg white. The heat
      induced changes on chicken OVM structure and antigenic properties were assessed
      at acidic, neutral and alkaline pH values. RESULTS: The fluorescence spectroscopy
      measurements indicated changes in the conformation of OVM caused by both pH and
      thermal treatment. The OVM molecule exhibited higher exposure of hydrophobic
      residues at 7.0, as indicated by the synchronous spectra, intrinsic fluorescence
      and quenching experiments. When heating the protein at pH 9.5, the molecular
      structure appeared more compact. The antigenic properties of OVM, estimated
      through the enzyme-linked immunosorbent assay, appeared not to be sensitive to
      heat at pH 7.0 and 4.5. Single molecule level investigations indicated that the
      secondary and tertiary structure of OVM was affected by the thermal treatment.
      CONCLUSIONS: Experimental results indicated over 90% reduction of the
      antigenicity at pH 9.5 and temperature of 100  degrees C. Significant changes of
      the linear epitopes exposure and location of the conformational epitopes were
      highlighted after performing heating molecular dynamics simulations of OVM from
      25  degrees C to 100  degrees C. (c) 2017 Society of Chemical Industry.

PMID- 29210458
TI  - Distribution of cardiac sodium channels in clusters potentiates ephaptic
      interactions in the intercalated disc.
AB  - KEY POINTS: It has been proposed that ephaptic conduction, relying on
      interactions between the sodium (Na+ ) current and the extracellular potential in
      intercalated discs, might contribute to cardiac conduction when gap junctional
      coupling is reduced, but this mechanism is still controversial. In intercalated
      discs, Na+ channels form clusters near gap junction plaques, but the functional
      significance of these clusters has never been evaluated. In HEK cells expressing
      cardiac Na+ channels, we show that restricting the extracellular space modulates
      the Na+ current, as predicted by corresponding simulations accounting for
      ephaptic effects. In a high-resolution model of the intercalated disc, clusters
      of Na+ channels that face each other across the intercellular cleft facilitate
      ephaptic impulse transmission when gap junctional coupling is reduced. Thus, our
      simulations reveal a functional role for the clustering of Na+ channels in
      intercalated discs, and suggest that rearrangement of these clusters in disease
      may influence cardiac conduction. ABSTRACT: It has been proposed that ephaptic
      interactions in intercalated discs, mediated by extracellular potentials,
      contribute to cardiac impulse propagation when gap junctional coupling is
      reduced. However, experiments demonstrating ephaptic effects on the cardiac Na+
      current (INa ) are scarce. Furthermore, Na+ channels form clusters around gap
      junction plaques, but the electrophysiological significance of these clusters has
      never been investigated. In patch clamp experiments with HEK cells stably
      expressing human Nav 1.5 channels, we examined how restricting the extracellular
      space modulates INa elicited by an activation protocol. In parallel, we developed
      a high-resolution computer model of the intercalated disc to investigate how the
      distribution of Na+ channels influences ephaptic interactions. Approaching the
      HEK cells to a non-conducting obstacle always increased peak INa at step
      potentials near the threshold of INa activation and decreased peak INa at step
      potentials far above threshold (7 cells, P = 0.0156, Wilcoxon signed rank test).
      These effects were consistent with corresponding control simulations with a
      uniform Na+ channel distribution. In the intercalated disc computer model,
      redistributing the Na+ channels into a central cluster of the disc potentiated
      ephaptic effects. Moreover, ephaptic impulse transmission from one cell to
      another was facilitated by clusters of Na+ channels facing each other across the
      intercellular cleft when gap junctional coupling was reduced. In conclusion, our
      proof-of-principle experiments demonstrate that confining the extracellular space
      modulates cardiac INa , and our simulations reveal the functional role of the
      aggregation of Na+ channels in the perinexus. These findings highlight novel
      concepts in the physiology of cardiac excitation.

PMID- 29210459
TI  - Phenolic Analysis and Theoretic Design for Chinese Commercial Wines'
      Authentication.
AB  - : To develop a robust tool for Chinese commercial wines' varietal, regional, and
      vintage authentication, phenolic compounds in 121 Chinese commercial dry red
      wines were detected and quantified by using high-performance liquid
      chromatography triple-quadrupole mass spectrometry (HPLC-QqQ-MS/MS), and
      differentiation abilities of principal component analysis (PCA), partial least
      squares discriminant analysis (PLS-DA), and orthogonal partial least squares
      discriminant analysis (OPLS-DA) were compared. Better than PCA and PLS-DA, OPLS
      DA models used to differentiate wines according to their varieties (Cabernet
      Sauvignon or other varieties), regions (east or west Cabernet Sauvignon wines),
      and vintages (young or old Cabernet Sauvignon wines) were ideally established.
      The S-plot provided in OPLS-DA models showed the key phenolic compounds which
      were both statistically and biochemically significant in sample differentiation.
      Besides, the potential of the OPLS-DA models in deeper sample differentiating of
      more detailed regional and vintage information of wines was proved optimistic. On
      the basis of our results, a promising theoretic design for wine authentication
      was further proposed for the first time, which might be helpful in practical
      authentication of more commercial wines. PRACTICAL APPLICATION: The phenolic data
      of 121 Chinese commercial dry red wines was processed with different statistical
      tools for varietal, regional, and vintage differentiation. A promising
      theoretical design was summarized, which might be helpful for wine authentication
      in practical situation.

PMID- 29210460
TI  - A Kinetic Approach to Evaluate the Structure-Based Performance of Antioxidants
      During Lipid Oxidation.
AB  - Thermal kinetic parameters of fish oil oxidation, as affected by o-hydroxyl, o
      methoxy, and alkyl ester derivatives of p-hydroxybenzoic acid in various
      concentrations (0.02% to 0.16%) at 35 to 55  degrees C, were calculated. The
      average extent of increase (2% to 10%) in the values of free energy of
      activation, ?G++ , as well as the average extent of change in the Arrhenius
      equation parameters, including activation energy (Ea , -40.5% to 13.6%) and
      frequency factor (A, -55.0% to 4.3%), could be employed well to show structure
      based performance of antioxidants. Temperature coefficient (TC ) and Q10 number,
      which were considered as the quantitative measures of thermal sensitivity of the
      lipid system, showed changes from -40.3% and -27.2% to 13.5% and 11.5%,
      respectively, in the presence of the antioxidants.

PMID- 29210461
TI  - Chronic pain in pachyonychia congenita: evidence for neuropathic origin.
AB  - BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant skin
      disease, with chronic pain being the most prominent complaint. Histological
      studies showing alterations in sensory innervation, along with reports on
      alterations in mechanical sensitivity, suggest that PC may be a form of
      neuropathy. OBJECTIVES: Here, for the first time, we aim to evaluate
      systematically the sensory function of patients with PC vs. controls, in order to
      investigate the pathophysiology of PC. METHODS: Patients (n = 62) and controls (n
      = 45) completed the McGill and Douleur Neuropathique-4 (DN4) questionnaires.
      Sensory testing included detection and pain thresholds, pathological sensations,
      conditioned pain modulation (CPM) and temporal summation of pain. RESULTS: A
      moderate-to-severe chronic pain in the feet, throbbing and stabbing in quality,
      was highly prevalent among patients with PC (86%) and was especially debilitating
      during weight bearing. In addition, the majority of patients had a DN4 score >= 4
      (62%), static allodynia (55%) and tingling (53%) in the feet. Compared with
      controls, patients with PC exhibited thermal and mechanical hypoaesthesia and
      mechanical hyperalgesia in the feet. CPM was reduced among the patients, and was
      associated with more enhanced mechanical hyperalgesia in the feet. The specific
      gene and nature of the causative mutation did not affect any of these features.
      CONCLUSIONS: Although thermal and mechanical hypoaesthesia may result from
      thicker skin, its presentation in painful regions, along with mechanical
      hyperalgesia and allodynia, point towards the possibility of neuropathic changes
      occurring in PC. The clinical features and DN4 scores support this possibility
      and therefore neuropathic pain medications may be beneficial for patients with
      PC.

PMID- 29210462
TI  - Vocational rehabilitation for enhancing return-to-work in workers with traumatic
      upper limb injuries.
AB  - BACKGROUND: Traumatic upper limb injury is a leading cause of work-related
      disability. After return-to-work (RTW), many survivors of injuries are able to
      regain a quality of life (QoL) comparable with the normal population. Since RTW
      plays an important role in economic productivity and regaining health-related
      QoL, enhancing RTW in workers with traumatic limb injuries is the primary goal of
      rehabilitation. Vocational rehabilitation has been commonly employed in the field
      of occupational safety and health to increase the number of injured people
      returning to the labour market, prevent illness, increase well-being, and reduce
      disability. OBJECTIVES: To assess the effects of vocational rehabilitation
      programmes for enhancing RTW in workers with traumatic upper limb injuries.
      SEARCH METHODS: This is an update of a Cochrane review previously published in
      2013. We updated our searches of the following databases: the Cochrane Central
      Register of Controlled Trials (CENTRAL; 2017, Issue 9), MEDLINE (to 30 August
      2017), EMBASE (to 3 September 2017), CINAHL (to 6 September 2017), and PsycINFO
      (to 6 September 2017), and we handsearched the references lists of relevant
      review articles. SELECTION CRITERIA: We aimed to include all randomised
      controlled trials (RCTs) comparing vocational rehabilitation with an alternative
      (control) intervention such as standard rehabilitation, a limited form of the
      vocational rehabilitation intervention (such as advice on RTW, referral
      information, or liaison with employer), or waiting-list controls. DATA COLLECTION
      AND ANALYSIS: Two authors independently inspected abstracts, and we obtained full
      papers when necessary. When the two authors disagreed about the inclusion of a
      study, we resolved disagreements by discussion. A third author arbitrated when
      necessary. MAIN RESULTS: Our updated search identified 466 citations. Based on
      assessments of their titles and abstracts, we decided to evaluate the full texts
      of five records; however, none met our inclusion criteria. AUTHORS' CONCLUSIONS:
      There is currently no high-quality evidence to support or refute the efficacy of
      vocational rehabilitation for enhancing RTW in workers with traumatic upper limb
      injuries. Since injured people in occupational settings frequently receive
      vocational rehabilitation with the aim of decreasing work disability, enhancing
      RTW, increasing productivity, and containing the welfare cost, further high
      quality RCTs assessing the efficacy of vocational rehabilitation for workers with
      traumatic upper limb injury are needed to fill this gap in knowledge.

PMID- 29210463
TI  - Fishy Odor and TMA Content Levels in Duck Egg Yolks.
AB  - : The differences between the trimethylamine (TMA) content levels in duck and
      chicken egg yolks under normal dietary conditions were compared. Moreover, the
      association between the polymorphisms of the duck FMO3 gene and TMA content
      levels in duck egg yolks was analyzed. Then, to detect the mutations associated
      with the fish-flavor trait, duck populations were selected for a high-choline
      diet experiment, which was followed by full-length sequencing of the FMO3 exons.
      The results showed that the TMA content levels in duck eggs (3.60 MUg/g) were
      significantly higher than those in chicken eggs (2.35 MUg/g) under normal dietary
      conditions (P < 0.01). With regard to the high-choline diet, the average TMA
      content levels in duck egg yolks (9.21 MUg/g; P < 0.01) increased significantly.
      Furthermore, 5 SNPs reported in Ensembl database were detected in duck FMO3
      exons. However, no mutation loci were found to be significantly associated with
      the TMA content levels in duck egg yolks. Besides, duck liver FMO3 mRNA
      expression levels were not associated with the TMA content levels. The results
      indicated that excessive TMA deposition in duck eggs is one of main factors
      causing the fishy odor in duck eggs, and the addition of choline in the ducks'
      diets was responsible for inducing an increase in the TMA content levels in duck
      eggs. PRACTICAL APPLICATION: Our study can help to diminish the fishy taste in
      duck eggs by reducing the amount of supplemented choline. Furthermore, this study
      laid a solid foundation for revealing the genetic factors involved in the fishy
      odor in duck eggs.

PMID- 29210465
TI  - 25 years of European Union (EU) quality schemes for agricultural products and
      foodstuffs across EU Member States.
AB  - Consumers are increasingly turning their attention to the quality and origin of
      products that they consume. European Union (EU) quality schemes are associated
      with a label, which was introduced to allow consumers to perform an informed
      choice and to protect producers from unfair practices. This present study
      provides an overview of the last 25 years of EU quality schemes [Protected
      Designations of Origin (PDO), Protected Geographical Indications (PGI) and
      Traditional Specialities Guaranteed (TSG)] on agricultural products and
      foodstuffs across the 28 EU Member States. According to the results, it was
      possible to conclude that Southern European countries have the highest number of
      registered products. The most used EU quality scheme is PGI, followed by PDO.
      Concerning the analysis of the evolution in the last 25 years, the number of
      registered products among EU Member States has increased significantly. The
      fruit, vegetables and cereals (fresh or processed) category is the one that
      accounts for the highest percentage (26.8%) of registered products, followed by
      cheeses and meat products (cooked, salted, smoked) categories, with 17.2% and
      13.5%, respectively. Further investigations should address consumer preferences,
      knowledge and attitudes, especially Northern European countries with a lower
      number of registered products. Moreover, the investigation and registration of
      products should be encouraged among all EU Member States to allow the maintenance
      of important elements of the history, culture and heritage of the local areas,
      regions and countries. (c) 2017 Society of Chemical Industry.

PMID- 29210464
TI  - Ca2+ and lipid signals hold hands at endoplasmic reticulum-plasma membrane
      contact sites.
AB  - Discovery of the STIM1 and Orai proteins as the principal components of store
      operated Ca2+ entry has drawn attention to contact sites between the endoplasmic
      reticulum (ER) and the plasma membrane (PM). Such contacts between adjacent
      membranes of different cellular organelles, primarily between the mitochondria
      and the ER, had already been known as the sites where Ca2+ released from the ER
      can be efficiently channelled to the mitochondria and also where
      phosphatidylserine synthesis and transfer takes place. Recent studies have
      identified contact sites between virtually every organelle and the ER and the
      functional importance of these small specialized membrane domains is increasingly
      recognized. Most recent developments have highlighted the role of
      phosphatidylinositol 4-phosphate gradients as critical determinants of the non
      vesicular transport of various lipids from the ER to other organelles such as the
      Golgi or PM. As we learn more about membrane contact sites it becomes apparent
      that Ca2+ is not only transported at these sites but also controls both the
      dynamics and the lipid transfer efficiency of these processes. Conversely, lipids
      are critical for regulating the Ca2+ entry process. This review will summarize
      some of the most exciting recent developments in this rapidly expanding research
      field.

PMID- 29210466
TI  - Influence of deficit irrigation and crop load on the yield and fruit quality in
      Wonderful and Mollar de Elche pomegranates.
AB  - BACKGROUND: The working hypothesis of the present study was that, by proper
      simultaneous control of irrigation (hydroSOStainable products) and crop load
      (thinning), it is possible to promote the accumulation of bioactive compounds and
      improve fruit appearance (size and weight). The effects of (i) irrigation status
      [T0, 120% ETc (estimated crop evapotranspiration); T1, 60% ETc during fruit
      growth and ripening] and (ii) crop load (A0, no thinning; A1, thinning) on yield
      and fruit quality were evaluated in two pomegranate cultivars (Wonderful, Wond
      and Mollar de Elche, ME). RESULTS: Thinning was effective in increasing the size
      and weight of fruits. Unfortunately, neither punicalagin, nor total polyphenolic
      content were positively affected by irrigation and thinning. T1A1 Wond fruits
      were characterized by high sugar content (glucose and fructose), together with
      high fruit size and weight. Furthermore, T1A1 ME fruits were characterized by
      high contents of alcohols and monoterpenoids (providing vegetal and citric flavor
      notes) and key sensory attributes (color, fruity and fresh pomegranate).
      CONCLUSION: The final recommendation was to use the treatment T1A1 [simultaneous
      combination of deficit irrigation during fruit growth and ripening (T1) and
      thinning (A1)], although the positive results were cultivar-dependent. (c) 2017
      Society of Chemical Industry.

PMID- 29210467
TI  - Influence of the quality of life and locus of control of mothers of disabled
      children on the oral health of their children.
AB  - AIM: To investigate whether quality of life of mothers is related to oral health
      of disabled children. METHOD: This is an analytical cross-sectional study, based
      on interviews with 49 mothers and oral clinical examination (DMFT and OHI-S) in
      children with disabilities from 2 to 6 years old, assisted by the Rehabilitation
      Center of Piracicaba, SP. Mothers answered WHOQOL BREF quality of life instrument
      and Multidimensional Health Locus of Control Scale. Data analysis was performed
      with descriptive statistics, Chi-square test, Fisher's exact test, and multiple
      logistic regression. RESULT: Most children of the sample were aged from 37 to 48
      months (40.81%) and presented neuropsychomotor development delay. Mothers
      reported (55.1%) that their interference in the health/illness of their children
      was a fortuitous process. The social relationships domain of WHOQOL BREF
      presented significant association (p = 0.0404) with DMFT index. CONCLUSION: We
      observed that quality of life of mothers can interfere in oral health of
      children, regarding social relationships.

PMID- 29210468
TI  - Marriage Transitions in Malawi Panel Data.

PMID- 29210470
TI  - Variable Implementation of Sexuality Education in Three Nigerian States.
AB  - In 2003, Nigeria adopted the Family Life and HIV Education (FLHE) sexuality
      education curriculum. Our analysis interrogates variation in sub-national
      implementation. We conducted 52 interviews with persons knowledgeable about the
      curriculum in three states-Kano, Lagos, and Niger-and reviewed publications on
      FLHE. In Kano, the socio-cultural context impeded implementation, but the
      persistence of innovative local champions resulted in some success. In Lagos, the
      cosmopolitan context, effective champions, funding by international donors, and a
      receptive government bureaucracy led to successful implementation. In Niger,
      despite a relatively conservative socio-cultural context, state bureaucratic
      bottlenecks overwhelmed proponents' efforts. In summary, the interaction of socio
      cultural context, domestic champions, adaptive capacity of state bureaucracies,
      and international funders explains variable implementation of FLHE. The Nigerian
      experience highlights the need for sexuality education proponents to anticipate
      and prepare for local opposition and bureaucratic barriers.

PMID- 29210471
TI  - Child Maltreatment, Problem Behaviors, and Neighborhood Attainment.
AB  - Using data from a prospective cohort design study of a group of children with
      documented histories of abuse and neglect (n = 908) and matched controls (n =
      667), this paper examines whether problem behaviors (e.g., prostitution, crime,
      school problems, and homelessness) in young adulthood explain the link between
      maltreatment in childhood and living in high-risk neighborhoods in middle
      adulthood. Problem behaviors were assessed at mean age of 29 and neighborhood
      characteristics were assessed at mean age of 40. Child maltreatment predicted
      living in less desirable neighborhoods in middle adulthood. Problem behaviors in
      young adulthood partially mediated the relationship between childhood
      maltreatment and residence in less desirable neighborhoods in middle adulthood.
      The direct paths from child maltreatment to neighborhoods were not significant
      for Black children. For White children, there was a direct relationship between
      child maltreatment and living in an economically disadvantaged neighborhood.
      Problem behaviors were a stronger mediator between child maltreatment and living
      in more disordered and less socially cohesive neighborhoods for Black children,
      while the problem behaviors were a stronger mediator for living in more
      economically disadvantaged and less socially cohesive neighborhoods for White
      children. Further research is needed to understand these racial differences.
      Interventions should focus on preventing problem behaviors to minimize the risk
      of residency in high-risk neighborhoods.

PMID- 29210472
TI  - Hospital pharmacists' and patients' views about what constitutes effective
      communication between pharmacists and patients.
AB  - OBJECTIVES: The study's objective was to explore hospital pharmacists' and
      patients' views about what constitutes effective communication exchanges between
      pharmacists and patients. METHODS: This was a novel theory-based qualitative
      study using semi-structured interviews to elicit patients' and pharmacists'
      perspectives. Pharmacists providing clinical pharmacy services in either
      inpatient or outpatient settings were recruited first. Eligible patients had been
      admitted to a study pharmacist's practice area and were prescribed three or more
      medications to manage a chronic disease(s). Following each pharmacist-patient
      medication counselling session, semi-structured interviews were held separately
      with patients and pharmacists. Participants were asked questions intended to
      explore their views about what constitutes an effective pharmacist-patient
      conversation. Audio recordings were transcribed verbatim, analysed using a
      process of inductive thematic analysis and then mapped to Communication
      Accommodation Theory strategies. Observational notes and reflexive note taking
      were conducted throughout. KEY FINDINGS: Twelve pharmacists each engaged four
      individual patients for a total of 48 pharmacist-patient conversations (resulting
      in 48 separate interviews with pharmacists and patients). An overall shared goal
      was the assurance of patients' confidence in managing their medications at home.
      Themes included shared colloquialisms/slang, well-explained information,
      engagement, established rapport and empowerment. Participants provided rich
      exemplars for each of the themes. CONCLUSIONS: Pharmacists and patients provided
      valuable insights about what makes pharmacist-patient interactions effective.
      Patient-identified preferences for pharmacist-patient exchanges may help guide
      pharmacy students and practitioners to engage patients in effective
      conversations.

PMID- 29210473
TI  - Analysis by metadynamics simulation of binding pathway of influenza virus M2
      channel blockers.
AB  - M2 protein of influenza A virus is a proton channel spanning the viral envelope.
      Activity of this proton channel is required for uncoating of viral particles and
      equilibrating the pH across the trans Golgi apparatus, which prevents
      conformational change in hemagglutinin. Amantadine, an anti-influenza A virus
      drug, inhibits M2 proton channel activity by binding to the channel pore;
      however, most currently circulating influenza A viruses are amantadine-resistant.
      The most prevalent resistant mutation is a substitution from Ser31 to Asn31 in
      M2. Further atomistic analysis of ligand-M2 complexes is needed to provide new
      approaches for the design of novel M2 channel blockers. Here, the free energy
      profiles of the binding kinetics of M2 channel blockers were examined by well
      tempered metadynamics simulations and it was found that amantadine first binds to
      Asp24 of S31 M2 and forms a metastable conformation. In contrast, the free energy
      profiles of adamantyl bromothiophene dual inhibitor with either S31 M2 or N31 M2
      are broad funnel-shaped curves, suggesting that adamantyl bromothiophene does not
      form metastable complexes with M2. The trajectory of well-tempered metadynamics
      simulations revealed that steric hindrance between adamantyl bromothiophene and
      S31 M2 interrupts formation of a metastable conformation at Asp24 and that a
      halogen bond between the bromine atom and N31 is responsible for pulling down the
      ligand to the channel pore of N31 M2 in the absence of a metastable state.
      Binding pathways of M2 channel blockers to M2 are here proposed on the basis of
      these findings; they may provide new approaches to designing further M2 channel
      blockers.

PMID- 29210474
TI  - Facilitated Oxygen Chemisorption in Heteroatom-Doped Carbon for Improved Oxygen
      Reaction Activity in All-Solid-State Zinc-Air Batteries.
AB  - Driven by the intensified demand for energy storage systems with high-power
      density and safety, all-solid-state zinc-air batteries have drawn extensive
      attention. However, the electrocatalyst active sites and the underlying
      mechanisms occurring in zinc-air batteries remain confusing due to the lack of in
      situ analytical techniques. In this work, the in situ observations, including X
      ray diffraction and Raman spectroscopy, of a heteroatom-doped carbon air cathode
      are reported, in which the chemisorption of oxygen molecules and oxygen
      containing intermediates on the carbon material can be facilitated by the
      electron deficiency caused by heteroatom doping, thus improving the oxygen
      reaction activity for zinc-air batteries. As expected, solid-state zinc-air
      batteries equipped with such air cathodes exhibit superior reversibility and
      durability. This work thus provides a profound understanding of the reaction
      principles of heteroatom-doped carbon materials in zinc-air batteries.

PMID- 29210475
TI  - A Rational Approach to Metal Loading of Organic Multi-Site Polymers: Illusion or
      Reality?
AB  - Since its identification as an independent topic after the first world war, the
      chemistry of (bio)polymers and macromolecules rapidly benefited from intense
      synthetic activities driven by contributors focusing on formulation and
      structural aspects. Satisfying rationalization and predictions concerning polymer
      organization, stability, and reactivity were, however, delayed until the late
      fifties, when physical chemists set the basis of an adapted thermodynamic
      modeling. The recent emergence of metal-containing (bio)organic polymers (i.e.,
      metallopolymers) thus corresponds to a logical extension of this field with the
      ultimate goal of combining the rich magnetic and optical properties of open-shell
      transition metals with the processability and structural variety of polymeric
      organic scaffolds. Since applications as energy storage materials, drug delivery
      vectors, shape-memory materials, and photonic devices can be easily envisioned
      for these materials, the development of metallopolymers is faced with some
      urgency in producing novel exploitable structures, while the rational control of
      their formation, organization, and transformation remains elusive. Caught between
      the sometimes antagonistic requirements of economic efficiency on one side and of
      scientific pertinence on the other side, the ongoing achievements in the control
      of the metal loadings of multi-site polymers are highlighted here with some
      tutorial discussions of luminescent lanthanidopolymers as proof-of-concept.

PMID- 29210477
TI  - The Role of Terminal Functionality in the Membrane and Antibacterial Activity of
      Peptaibol-Mimetic Aib Foldamers.
AB  - Peptaibols are peptide antibiotics that typically feature an N-terminal acetyl
      cap, a C-terminal aminoalcohol, and a high proportion of alpha-aminoisobutyric
      acid (Aib) residues. To establish how each feature might affect the membrane
      activity of peptaibols, biomimetic Aib foldamers with different lengths and
      terminal groups were synthesised. Vesicle assays showed that long foldamers
      (eleven Aib residues) with hydrophobic termini had the highest ionophoric
      activity. C-terminal acids or primary amides inhibited activity, while
      replacement of an N-terminal acetyl with an azide group made little difference.
      Crystallography showed that N3 Aib11 CH2 OTIPS folded into a 310 helix 2.91 nm
      long, which is close to the bilayer hydrophobic width. Planar bilayer conductance
      assays showed discrete ion channels only for N-acetylated foldamers. However long
      foldamers with hydrophobic termini had the highest antibacterial activity,
      indicating that ionophoric activity in vesicles was a better indicator of
      antibacterial activity than the observation of discrete ion channels.

PMID- 29210476
TI  - Delayed revascularization of islets after transplantation by IL-6 blockade in pig
      to non-human primate islet xenotransplantation model.
AB  - BACKGROUND: Pancreatic islet transplantation is currently proven as a promising
      treatment for type 1 diabetes patients with labile glycemic control and severe
      hypoglycemia unawareness. Upon islet transplantation, revascularization is
      essential for proper functioning of the transplanted islets. As IL-6 is important
      for endothelial cell survival and systemic inflammation related to xenograft, the
      effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the
      transplanted islets was examined in pig to non-human primate islet
      xenotransplantation model. Also, the endothelial cell origin in a new vessel of
      the transplanted pig islets was determined. METHODS: Pig islets were isolated
      from designated pathogen-free (DPF) SNU miniature pigs and transplanted via
      portal vein into five streptozotocin-induced diabetic monkeys. One group (n = 2,
      basal group) was treated with anti-thymoglobulin (ATG), anti-CD40 antibody
      (2C10R4), sirolimus, and tacrolimus, and the other group was additionally given
      tocilizumab on top of basal immunosuppression (n = 3, Tocilizumab group). To
      confirm IL-6 blocking effect, C-reactive protein (CRP) levels and serum IL-6
      concentration were measured. Scheduled biopsy of the margin of the posterior
      segment right lobe inferior of the liver was performed at 3 weeks after
      transplantation to assess the degree of revascularization of the transplanted
      islets. Immunohistochemical staining using anti-insulin, anti-CD31 antibodies,
      and lectin IB4 was conducted to find the origin of endothelial cells in the islet
      graft. RESULTS: CRP significantly increased at 1~2 days after transplantation in
      Basal group, but not in Tocilizumab group, and higher serum IL-6 concentration
      was measured in latter group, showing the biological potency of tocilizumab. In
      Basal group, well-developed endothelial cells were observed on the peri- and
      intraislet area, whereas the number of CD31+ cells in the intraislet space was
      significantly reduced in Tocilizumab group. Finally, new endothelial cells in the
      pig islet graft were positive for CD31, but not for lectin IB4, suggesting that
      they are originated from the recipient monkey. CONCLUSIONS: Our results
      demonstrated that tocilizumab can delay revascularization of the transplanted
      islet, although this effect had no significant correlation to the overall islet
      graft survival. In the pig to NHP islet xenotransplantation model, the
      endothelial cells from recipient monkey form new blood vessels in and around pig
      islets.

PMID- 29210478
TI  - Type 2 diabetes specifically attenuates purinergic skin vasodilatation without
      affecting muscarinic and nicotinic skin vasodilatation and sweating.
AB  - NEW FINDINGS: What is the central question of this study? It remains to be
      determined whether type 2 diabetes attenuates muscarinic and nicotinic cutaneous
      vasodilatation and sweating as well as purinergic cutaneous vasodilatation. What
      is the main finding and its importance? We show that type 2 diabetes specifically
      attenuates purinergic cutaneous vasodilatation without influencing muscarinic and
      nicotinic cutaneous vasodilatation and sweating. Our results provide valuable new
      information regarding the receptor-specific influence of type 2 diabetes on
      microvascular and sudomotor function. ABSTRACT: The present study evaluated
      whether type 2 diabetes (T2D) attenuates muscarinic and/or nicotinic cutaneous
      vasodilatation and sweating as well as purinergic cutaneous vasodilatation.
      Cutaneous vascular conductance and sweat rate were evaluated in 12 healthy non
      diabetic older adults (Control, 60 +/- 8 years) and 13 older adults with T2D (62
      +/- 10 years) at three intradermal forearm skin sites perfused with the
      following: (i) methacholine (muscarinic receptor agonist, five doses: 0.0125,
      0.25, 5, 100 and 2000 mm); (ii) nicotine (nicotinic receptor agonist, five doses:
      1.2, 3.6, 11, 33 and 100 mm); or (iii) ATP (purinergic receptor agonist, five
      doses: 0.03, 0.3, 3, 30 and 300 mm). Each agonist was administered for 25 min per
      dose. At the end of the protocol, 50 mm sodium nitroprusside was administered to
      all skin sites to elicit maximal cutaneous vasodilatation. Cutaneous vascular
      conductance during methacholine and nicotine administration did not differ
      between groups (all P > 0.05). In contrast, cutaneous vascular conductance during
      administration of 30 mm (42 +/- 28 versus 63 +/- 26% maximum, P <= 0.05) and 300
      mm ATP (56 +/- 24 versus 71 +/- 20% maximum, P <= 0.05) was attenuated in
      individuals with T2D in comparison to the Control participants. Furthermore,
      cutaneous vascular conductance during administration of 50 mm sodium
      nitroprusside was lower in individuals with T2D relative to Control subjects (P =
      0.04). Methacholine- and nicotine-induced sweating was similar between groups
      (all P > 0.05). Thus, T2D attenuates purinergic cutaneous vasodilatation without
      affecting muscarinic and nicotinic cutaneous vascular and sweating responses.

PMID- 29210479
TI  - Origin of Fracture-Resistance to Large Volume Change in Cu-Substituted Co3 O4
      Electrodes.
AB  - The electrode materials conducive to conversion reactions undergo large volume
      change in cycles which restrict their further development. It has been
      demonstrated that incorporation of a third element into metal oxides can improve
      the cycling stability while the mechanism remains unknown. Here, an in situ and
      ex situ electron microscopy investigation of structural evolutions of Cu
      substituted Co3 O4 supplemented by first-principles calculations is reported to
      reveal the mechanism. An interconnected framework of ultrathin metallic copper
      formed provides a high conductivity backbone and cohesive support to accommodate
      the volume change and has a cube-on-cube orientation relationship with Li2 O. In
      charge, a portion of Cu metal is oxidized to CuO, which maintains a cube-on-cube
      orientation relationship with Cu. The Co metal and oxides remain as nanoclusters
      (less than 5 nm) thus active in subsequent cycles. This adaptive architecture
      accommodates the formation of Li2 O in the discharge cycle and underpins the
      catalytic activity of Li2 O decomposition in the charge cycle.

PMID- 29210480
TI  - Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET
      Traceable Drug Release.
AB  - Trans-activating transcriptional activator (TAT), a cell-penetrating peptide, is
      extensively used for facilitating cellular uptake and nuclear targeting of drug
      delivery systems. However, the positively charged TAT peptide strongly interacts
      with serum components and undergoes substantial phagocytosis by the
      reticuloendothelial system, causing a short blood circulation in vivo. In this
      work, an acid-active tumor targeting nanoplatform DA-TAT-PECL is developed to
      inhibit the nonspecific interactions of TAT in the bloodstream. 2,3
      dimethylmaleic anhydride (DA) is used to convert the TAT's amines to carboxylic
      acid; the resulting DA-TAT is conjugated to poly(ethylene glycol)-poly(epsilon
      caprolactone) (PEG-PCL, PECL) to get DA-TAT-PECL. After self-assembly into
      polymeric micelles, they are capable of circulating in the physiological
      condition for a long time and promoting cell penetration upon accumulation at the
      tumor site and deshielding the DA group. Moreover, camptothecin (CPT) is used as
      the anticancer drug and modified into a dimer (CPT)2 -ss-Mal, in which two CPT
      molecules are connected by a reduction-labile maleimide thioether bond. The
      Forster resonance energy transfer signal between CPT and maleimide thioether bond
      is monitored to visualize the drug release process, and effective targeted
      delivery of antitumor drugs is demonstrated. This pH/reduction dual-responsive
      micelle system provides a new platform for high fidelity cancer therapy.

PMID- 29210481
TI  - A Toroidal Metamaterial Switch.
AB  - Toroidal dipole is a localized electromagnetic excitation that plays an important
      role in determining the fundamental properties of matter due to its unique
      potential to excite nearly nonradiating charge-current configuration. Toroidal
      dipoles are recently discovered in metamaterial systems where it is shown that
      these dipoles manifest as poloidal currents on the surface of a torus and are
      distinctly different from the traditional electric and magnetic dipoles. Here, an
      active toroidal metamaterial switch is demonstrated in which the toroidal dipole
      can be dynamically switched to the fundamental electric dipole or magnetic
      dipole, through selective inclusion of active elements in a hybrid metamolecule
      design. Active switching of nonradiating toroidal configuration into highly
      radiating electric and magnetic dipoles can have significant impact in
      controlling the electromagnetic excitations in free space and matter that can
      have potential applications in designing efficient lasers, sensors, filters, and
      modulators.

PMID- 29210482
TI  - Genomic analysis of a case of agminated Spitz nevi and congenital-pattern nevi
      arising in extensive nevus spilus.
AB  - Nevus spilus is a melanocytic neoplasm characterized by a tan macular background
      punctuated by multiple hyperpigmented macules or papules that represent various
      types of nevi. These include junctional and compound nevi, Spitz nevi, and rarely
      blue nevi. We report a unique case of widespread, multiple nevi spili giving rise
      to agminated Spitz nevi and congenital-pattern compound nevi. We performed
      genetic analysis to further characterize the mutational profile of this rare
      entity.

PMID- 29210483
TI  - The position of reporting guidelines in qualitative nursing research.

PMID- 29210484
TI  - A Molecular Pillar Approach To Grow Vertical Covalent Organic Framework
      Nanosheets on Graphene: Hybrid Materials for Energy Storage.
AB  - Hybrid 2D-2D materials composed of perpendicularly oriented covalent organic
      frameworks (COFs) and graphene were prepared and tested for energy storage
      applications. Diboronic acid molecules covalently attached to graphene oxide (GO)
      were used as nucleation sites for directing vertical growth of COF-1 nanosheets
      (v-COF-GO). The hybrid material has a forest of COF-1 nanosheets with a thickness
      of 3 to 15 nm in edge-on orientation relative to GO. The reaction performed
      without molecular pillars resulted in uncontrollable growth of thick COF-1
      platelets parallel to the surface of GO. The v-COF-GO was converted into a
      conductive carbon material preserving the nanostructure of precursor with
      ultrathin porous carbon nanosheets grafted to graphene in edge-on orientation. It
      was demonstrated as a high-performance electrode material for supercapacitors.
      The molecular pillar approach can be used for preparation of many other 2D-2D
      materials with control of their relative orientation.

PMID- 29210485
TI  - A novel finding of oligodontia and ankyloglossia in a 14-year-old with Floating
      Harbor syndrome.
AB  - Floating-Harbor syndrome (FHS) is a rare genetic condition characterized by
      distinct facial features, short stature and delayed skeletal development. Here we
      present case of a 14-year-old boy with short stature, typical facial features,
      impaired voice quality, clinodactyly, cryptorchidism and unilateral agenesis of
      kidney. In addition he had oligodontia and ankyloglossia with features suggestive
      of FHS. Treatment rendered was restoration of caries, application of pit and
      fissure sealants followed by frenectomy. The purpose of this report is to
      highlight the oral developmental anomalies and the management of a patient with
      FHS and to add to the current knowledge of the literature on this syndrome.

PMID- 29210486
TI  - 4D Printed Actuators with Soft-Robotic Functions.
AB  - Soft matter elements undergoing programed, reversible shape change can contribute
      to fundamental advance in areas such as optics, medicine, microfluidics, and
      robotics. Crosslinked liquid crystalline polymers have demonstrated huge
      potential to implement soft responsive elements; however, the complexity and size
      of the actuators are limited by the current dominant thin-film geometry
      processing toolbox. Using 3D printing, stimuli-responsive liquid crystalline
      elastomeric structures are created here. The printing process prescribes a
      reversible shape-morphing behavior, offering a new paradigm for active polymer
      system preparation. The additive character of this technology also leads to
      unprecedented geometries, complex functions, and sizes beyond those of typical
      thin-films. The fundamental concepts and devices presented therefore overcome the
      current limitations of actuation energy available from thin-films, thereby
      narrowing the gap between materials and practical applications.

PMID- 29210487
TI  - Protection Group Effects During alpha,gamma-Diol Lignin Stabilization Promote
      High-Selectivity Monomer Production.
AB  - Protection groups were introduced during biomass pretreatment to stabilize
      lignin's alpha,gamma-diol group during its extraction and prevent its
      condensation. Acetaldehyde and propionaldehyde stabilized the alpha,gamma-diol
      without any aromatic ring alkylation, which significantly increased final product
      selectivity. The subsequent hydrogenolysis catalyzed by Pd/C generated lignin
      monomers at near-theoretical yields based on Klason lignin (48 % from birch, 20 %
      from spruce, 70 % from high-syringyl transgenic poplar), and with high
      selectivity to a single 4-n-propanolsyringol product (80 %) in the case of the
      poplar. Unlike direct hydrogenation of native wood, hydrogenolysis of protected
      lignin with Ni/C also led to high selectivity to this single product (78 %),
      paving the way to high-selectivity lignin upgrading with base metal catalysts.
      The use of extracted lignin facilitated valorization of polysaccharides, leading
      to high yields of all three major biomass polymers to a single major product.

PMID- 29210488
TI  - Acute polyneuromyopathy with respiratory failure secondary to monensin
      intoxication in a dog.
AB  - OBJECTIVE: To describe a successfully managed case of polyneuropathy and
      respiratory failure secondary to presumed monensin intoxication. CASE SUMMARY: A
      9-month-old Australian Shepherd was evaluated for progressive generalized
      weakness and respiratory distress. Several days preceding presentation, the dog
      was seen playing with a monensin capsule, and had free access to a barn where the
      product was stored and where chewed capsules were subsequently found. The dog was
      presented with flaccid tetraparesis, hyperthermia, and severe respiratory
      distress. Bloodwork and urinalysis revealed marked increase in serum creatine
      kinase concentration and presumed myoglobinuria. Cardiac troponin I level was
      markedly increased. Management included mechanical ventilation for 5 days, fluid
      therapy, active cooling, antimicrobial therapy, analgesia, gastroprotectants,
      antiemetics, enteral feedings, continuous nursing care, and physiotherapy.
      Intravenous lipid rescue therapy was administered with lack of improvement in
      respiratory function and muscle strength. The patient completely recovered and
      was discharged after 12 days of hospitalization. NEW OR UNIQUE INFORMATION
      PROVIDED: Monensin intoxication should be considered in the differential
      diagnosis of acute polyneuromyopathy and respiratory failure in dogs with access
      to this compound. Respiratory failure secondary to monensin intoxication does not
      necessarily carry a poor prognosis if mechanical ventilation can be provided as a
      bridge until return of respiratory function is achieved.

PMID- 29210489
TI  - Effects of Temperature and Photorepair Radiation on a Marine Ciliate Exposed to
      UVB Radiation.
AB  - The influences of intensity and repeated exposure to ultraviolet-B radiation
      (UVB), photoreactivating repair radiation (PRR), and temperature on the
      scuticociliate Parauronema acutum were explored under laboratory conditions.
      Population growth was negatively affected after exposure to the equivalent of one
      sunny summer day of ambient UVB, especially in the absence of PRR. Repeated daily
      exposure to UVB severely compromised ciliate survival. UVB-exposed treatments
      without PRR recovered slower and reached lower final abundances than treatments
      receiving PRR. Reducing the daily UVB exposure approximately 25% improved ciliate
      recovery after exposure. In the single exposure treatments, temperature effects
      were not consistent, except that growth was slowest for control and treatments at
      the lowest temperature (15  degrees C). These data suggest that dark repair
      and/or photoprotection are present in P. acutum, but photoenzymatic repair was
      the more effective mechanism in reversing UVB damage. Repeated exposure
      treatments without PRR had zero or declining growth at all temperatures (15, 20
      and 25  degrees C), as did those with PRR at 15  degrees C. Significant
      temperature/dose differences were identified in the repeated exposure treatments;
      ciliates subjected to the higher UVB intensity with PRR survived only at 25 
      degrees C, while ciliate populations under reduced UVB increased at 20 and 25 
      degrees C.

PMID- 29210490
TI  - Thermally Labile Self-Healable Branched Gel Networks Fabricated by New
      Macromolecular Engineering Approach Utilizing Thermoreversibility.
AB  - A new approach based on macromolecular engineering through thermoreversibility is
      reported to fabricate the engineered gel networks of thermally labile branched
      polymers exhibiting robust self-healing. This approach centers on the synthesis
      of linear polymers having Diels-Alder cycloadducts in the backbones (DALPs)
      through A2 + B2 step-growth polymerization of a difunctional furan and a
      difunctional maleimide. Reactive mixtures of the resulting DALP with a polyfuran
      at elevated temperature allow for the formation of engineered gel networks
      through random dissociation of backbone DA linkages of the DALPs by retro-Diels
      Alder reaction, followed by their reconstruction in the presence of polyfuran
      (with functionality > 2) by Diels-Alder reaction. Optimizing the ratio of furan
      to DA linkages in the reactive mixtures yields thermally labile networks
      exhibiting excellent thermoreversibility. Effective self-healing demonstrated
      with reconstruction from two separate pieces and complete void filling on surface
      cuts as well as recovery of healing viscoelasticity suggest that the new
      macromolecular engineering approach offers versatility toward the development of
      thermally mendable thermosets.

PMID- 29210491
TI  - Multicompartment Vesicles Formation by Emulsification-Induced Assembly of
      Poly(ethylene oxide)-block-poly(epsilon-caprolactone) and Their Dual-Loading
      Capability.
AB  - Emulsification-induced assembly is employed to allow structural diversity in
      nanoaggregates of a biocompatible amphiphilic polymer, poly(ethylene oxide)-block
      poly(epsilon-caprolactone). Onion-like vesicles are efficiently produced by
      tuning the interfacial instability of the oil-in-water emulsion. The increase in
      the polymer concentration and use of the organic solvents with a low interfacial
      tension between water and the oil phase lead to a strong tendency of emulsion
      droplets to generate the onion-like vesicles. The vesicular networks and fibers
      are also obtained by controlling the concentration and type of the surfactant,
      respectively. Interestingly, the onion-like vesicles composed of alternating
      walls and water channels and the vesicular networks originated from a string of
      vesicles show dual-loading ability for hydrophobic and hydrophilic dyes but
      slightly different loading capacities. This result indicates that the development
      of a methodology to fabricate well-defined, unique nanostructures, such as
      multivesicular and multilamellar nanostructures, and subsequent elucidation of
      their structure-property relationships can provide useful guidance in the design
      of novel biomedical materials.

PMID- 29210492
TI  - Well-paid nurses are good nurses.
AB  - Some recent articles suggest that increasing wage in the nursing market with the
      aim of reducing shortage can negatively impact on the average ability and
      motivation of applicants attracted and, in turn, on the average quality of care.
      This finding is at odds with empirical evidence and has been criticized on the
      grounds that nurses' motivation is modeled in an overly simplistic way. This
      paper provides a novel theoretical framework where the orientation of nurses'
      motivation-intrinsic versus extrinsic-is taken into account, and the precise
      distinction between intrinsic and extrinsic motivation is delineated on the basis
      of self-determination and person-environment fit theories. Conditions are derived
      under which high wages attract able and motivated individuals, thus maximizing
      the average quality of care.

PMID- 29210493
TI  - Custom 3D Printable Silicones with Tunable Stiffness.
AB  - Silicone elastomers have broad versatility within a variety of potential advanced
      materials applications, such as soft robotics, biomedical devices, and
      metamaterials. A series of custom 3D printable silicone inks with tunable
      stiffness is developed, formulated, and characterized. The silicone inks exhibit
      excellent rheological behavior for 3D printing, as observed from the printing of
      porous structures with controlled architectures. Herein, the capability to tune
      the stiffness of printable silicone materials via careful control over the
      chemistry, network formation, and crosslink density of the ink formulations in
      order to overcome the challenging interplay between ink development, post
      processing, material properties, and performance is demonstrated.

PMID- 29210494
TI  - Systematic review of aged care interventions for older prisoners.
AB  - OBJECTIVE: The care of older prisoners is a growing problem. This review examined
      aged care interventions in prisons. METHODS: A systematic review was conducted
      following preferred reporting items for systematic reviews and meta-analyses
      guidelines. A total of 1186 abstracts were screened for inclusion. Quantitative
      and qualitative studies were included. RESULTS: Two quantitative studies and five
      qualitative studies examined aged care interventions (n = 7). An intervention
      involving physical health activities was not effective in reducing distress
      compared to a control, and an intervention of psychosocial, physical and
      spiritual health activities for veterans was not effective when compared to a
      comparison group. Qualitative analysis generated themes that apply to best
      practices: addressing older prisoners' needs, identifying barriers for older
      prisoners and staff, considering the prison culture, program delivery and
      cultivating older prisoners and staff attitudes. CONCLUSION: This review found no
      significant interventions in prisons. However, the qualitative findings showed
      evidence of best practice.

PMID- 29210495
TI  - Total Synthesis of Bryostatin 8 Using an Organosilane-Based Strategy.
AB  - Convergent total synthesis of bryostatin 8 has been accomplished by an
      organosilane-based strategy. The C ring is constructed stereoselectively through
      a geminal bis(silane)-based [1,5]-Brook rearrangement, and the B ring through
      geminal bis(silane)-based Prins cyclization, thus efficiently joining the
      northern and southern parts of the molecule.

PMID- 29210496
TI  - Structure Re-determination and Superconductivity Observation of Bulk 1T MoS2.
AB  - 2H MoS2 has been intensively studied because of its layer-dependent electronic
      structures and novel physical properties. Though the metastable 1T MoS2 with a
      [MoS6 ] octahedron was observed over the microscopic area, the true crystal
      structure of 1T phase has not been strictly determined. Moreover, the true
      physical properties have not been demonstrated from experiments owing to the
      challenge for the preparation of pure 1T MoS2 crystals. 1T MoS2 single crystals
      were successfully synthesized and the crystal structure of 1T MoS2 re-determined
      from single-crystal X-ray diffraction. 1T MoS2 crystallizes in the space group
      P3? m1 with a cell of a=b=3.190(3) A and c=5.945(6) A. The individual MoS2 layer
      consists of MoS6 octahedra sharing edges with each other. More surprisingly, the
      bulk 1T MoS2 crystals undergo a superconducting transition of Tc =4 K, which is
      the first observation of superconductivity in pure 1T MoS2 phase.

PMID- 29210497
TI  - Dengue in Rio Grande do Sul, Brazil: 2014 to 2016.
AB  - The first autochthonous dengue case in Rio Grande do Sul (RS), Southern Brazil,
      occurred in 2007. In 2008 and 2009, only imported cases were reported in RS, but
      from 2010 to 2013, reports of autochthonous infections increased significantly.
      This study analyzes and discusses laboratory, demographic, and clinical data
      regarding dengue cases in RS, from 2014 to 2016. This study analyzed 13,420 serum
      samples from notified patients with suspicion of dengue fever in RS from 2014 to
      2016. Seasonality of positive cases, viral serotypes, and clinical and
      epidemiological aspects were analyzed. There was no difference in gender (P =
      .4); dengue fever occurred mainly in adults, with similar distribution among age
      groups. The number of dengue virus (DENV) cases increased from 89 cases in 2014
      to 2518 in 2016. Dengue virus 1 was the most prevalent circulating serotype
      during this period (97.5% of cases). Dengue virus infections show peaks in March
      and April (late summer and early autumn), after periods of high temperatures and
      rainfall. In 2014, dengue cases were concentrated in the northwestern and eastern
      regions of RS, and in 2015 and 2016, the northern region also confirmed a high
      number of cases. With increase in DENV circulation in RS, a rise in the number of
      autochthonous infections was also observed, mainly in highly urbanized areas.
      This study revealed that circulation of DENV in RS increased significantly in
      2015 and 2016, with a rise in the number of autochthonous infections and
      cocirculation with Chikungunya and Zika viruses, recently introduced into RS.

PMID- 29210498
TI  - Ultrahigh Flux Composite Hollow Fiber Membrane via Highly Crosslinked PDMS for
      Recovery of Hydrocarbons: Propane and Propene.
AB  - In order to make membrane separation technologies more cost-competitive with the
      well-established processes that are energy intensive for gas/vapor separation, a
      defect-free membrane with a high gas permeance is necessary. However, it remains
      challenging to meet these needs because of the difficulties in developing a
      suitable material and process that are economical and practical. Herein, a novel
      and straightforward strategy is presented to produce a defect-free hollow fiber
      composite membrane using a highly crosslinked polydimethylsiloxane (PDMS)
      synthesized by using a postcrosslinking method. The PDMS can be directly coated
      on a polyacrylonitrile (PAN) membrane substrate, and the resultant PDMS/PAN
      composite membrane has ultrahigh C3 H8 and C3 H6 permeances that are higher than
      10 000 and 11 000 GPU, respectively, and the corresponding permselectivity of C3
      H8 /N2 and C3 H6 /N2 are about 21 and 24, respectively. The newly developed
      methods and materials may open up a new cost-effective method to fabricate next
      generation composite membranes for the recovery of hydrocarbons, organic vapors,
      and gases.

PMID- 29210499
TI  - Supramolecular "Step Polymerization" of Preassembled Micelles: A Study of
      "Polymerization" Kinetics.
AB  - In nature, sophisticated functional materials are created through hierarchical
      self-assembly of nanoscale motifs, which has inspired the fabrication of man-made
      materials with complex architectures for a variety of applications. Herein, a
      kinetic study on the self-assembly of spindle-like micelles preassembled from
      polypeptide graft copolymers is reported. The addition of dimethylformamide and,
      subsequently, a selective solvent (water) can generate a "reactive point" at both
      ends of the spindles as a result of the existence of structural defects, which
      induces the "polymerization" of the spindles into nanowires. Experimental results
      combined with dissipative particle dynamics simulations show that the
      polymerization of the micellar subunits follows a step-growth polymerization
      mechanism with a second-order reaction characteristic. The assembly rate of the
      micelles is dependent on the subunit concentration and on the activity of the
      reactive points. The present work reveals a law governing the self-assembly
      kinetics of micelles with structural defects and opens the door for the
      construction of hierarchical structures with a controllable size through
      supramolecular step polymerization.

PMID- 29210500
TI  - Stretchable Fluorescent Polyfluorene/Acrylonitrile Butadiene Rubber Blend
      Electrospun Fibers through Physical Interaction and Geometrical Confinement.
AB  - Stretchable light-emitting polymers are important for wearable electronics;
      however, the development of intrinsic stretchable light-emitting materials with
      great performance under large applied strain is the most critical challenge.
      Herein, this study demonstrates the fabrication of stretchable fluorescent
      poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctyl
      fluorene)]/acrylonitrile butadiene rubber (PFN/NBR) blend nanofibers using the
      uniaxial electrospinning technique. The physical interaction of PFN with NBR and
      the geometrical confinement of nanofibers are employed to reduce PFN aggregation,
      leading to the high photoluminescence quantum yield of 35.7%. Such fiber mat film
      shows stable blue emission at the 50% strain for 200 stretching/release cycles,
      which has potential applications in smart textiles.

PMID- 29210501
TI  - Women's Experiences of Seeking and Receiving Psychological and Psychosocial
      Interventions for Postpartum Depression: A Systematic Review and Thematic
      Synthesis of the Qualitative Literature.
AB  - INTRODUCTION: Postpartum depression (PPD) is a serious maternal disorder that can
      have adverse effects on maternal and infant health. The importance of offering
      effective and acceptable treatments is well recognized, particularly given the
      numerous barriers women in many settings face in accessing interventions for PPD.
      The aim of this systematic review was to synthesize qualitative research
      exploring women's experiences of professional psychological and psychosocial
      support for PPD. METHODS: A systematic review of the literature was conducted in
      April 2017 by searching 5 electronic databases (CINAHL, MEDLINE, PubMed, Ovid,
      and Web of Science). Qualitative research studies published in English that
      explored women's experiences of professional psychosocial support for PPD were
      included, whereas studies exploring women's experiences of antidepressant
      medication only were excluded. Seventeen articles met inclusion criteria and were
      appraised for methodologic quality. Data were synthesized using the interpretive
      thematic synthesis method. RESULTS: Four main themes were identified: the process
      of help-seeking, barriers to seeking and accepting support, valued aspects of
      support, and outcomes. Women found the process of seeking help difficult, with
      several barriers preventing them from both seeking and accepting professional
      support. Despite this, women described the support received as beneficial and
      particularly valued the therapeutic relationship. Women reported 1) feeling more
      positive and confident after receiving a psychological and/or psychosocial
      intervention and 2) experiencing better relationships with their infant and other
      family members. DISCUSSION: Although seeking and accepting professional support
      for PPD was a difficult process, women highly valued mental health care support
      and perceived it as beneficial. Clinical services should aim to address the
      barriers women face in accessing mental health care and empower women to feel in
      control throughout the process, offering interventions appropriate to each
      woman's personal circumstance.

PMID- 29210502
TI  - Three-Dimensional Static Articulation Accuracy of Virtual Models-Part II: Effect
      of Model Scanner-CAD Systems and Articulation Method.
AB  - PURPOSE: Accurate maxillomandibular relationship transfer is important for
      CAD/CAM prostheses. This study compared the 3D-accuracy of virtual model static
      articulation in three laboratory scanner-CAD systems (Ceramill Map400 [AG], inEos
      X5 [SIR], Scanner S600 Arti [ZKN]) using two virtual articulation methods:
      mounted models (MO), interocclusal record (IR). MATERIALS AND METHODS: The master
      model simulated a single crown opposing a 3-unit fixed partial denture. Reference
      values were obtained by measuring interarch and interocclusal reference features
      with a coordinate measuring machine (CMM). MO group stone casts were articulator
      mounted with acrylic resin bite registrations while IR group casts were hand
      articulated with poly(vinyl siloxane) bite registrations. Five test model sets
      were scanned and articulated virtually with each system (6 test groups, 15 data
      sets). STL files of the virtual models were measured with CMM software. dRR , dRC
      , and dRL , represented interarch global distortions at right, central, and left
      sides, respectively, while dRM , dXM , dYM , and dZM represented interocclusal
      global and linear distortions between preparations. RESULTS: Mean interarch 3D
      distortion ranged from -348.7 to 192.2 MUm for dRR , -86.3 to 44.1 MUm for dRC ,
      and -168.1 to 4.4 MUm for dRL . Mean interocclusal distortion ranged from -257.2
      to -85.2 MUm for dRM , -285.7 to 183.9 MUm for dXM , -100.5 to 114.8 MUm for dYM
      , and -269.1 to -50.6 MUm for dZM . ANOVA showed that articulation method had
      significant effect on dRR and dXM , while system had a significant effect on dRR
      , dRC , dRL , dRM , and dZM . There were significant differences between 6 test
      groups for dRR, dRL dXM , and dZM . dRR and dXM were significantly greater in AG
      IR, and this was significantly different from SIR-IR, ZKN-IR, and all MO groups.
      CONCLUSIONS: Interarch and interocclusal distances increased in MO groups, while
      they decreased in IR groups. AG-IR had the greatest interarch distortion as well
      as interocclusal superior-inferior distortion. The other groups performed
      similarly to each other, and the overall interarch distortion did not exceed
      0.7%. In these systems and articulation methods, interocclusal distortions may
      result in hyper- or infra-occluded prostheses.

PMID- 29210504
TI  - Endoscopic modified Lothrop procedure after failure of primary endoscopic sinus
      surgery: a meta-analysis.
AB  - BACKGROUND: The endoscopic modified Lothrop procedure (EMLP) has been used as a
      salvage technique for frontal sinusitis following failed endoscopic sinus surgery
      (ESS). We aim to examine the safety and efficacy of the EMLP following failure of
      primary ESS. METHODS: All English-language publications from 2000 to 2016
      reporting the use of EMLP after primary ESS were identified using the PubMed
      database and evaluated per Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) guidelines. Random effects summaries of patient
      demographics, comorbidities, and surgical outcomes were obtained through meta
      analysis. RESULTS: Eleven studies constituting 778 patients were included and
      86.5% had chronic rhinosinusitis (CRS). Mean follow-up duration was 28.4 months.
      The mean number of surgeries prior to EMLP was 3.5. Symptom improvement was
      reported in 82.3%. Subgroup analysis of 7 studies in which all 357 patients had
      CRS revealed a mean follow-up of 31.5 months. Symptom improvement occurred in
      75.9% of cases and 23.1% experienced polyp recurrence. The cerebrospinal fluid
      leak rate was 2.5%. Restenosis of the neo-ostium occurred in 17.1% with complete
      closure occurring in 3.9% of cases. The reoperation rate after EMLP was 9.0%.
      Aspirin sensitivity was associated with an increased risk of cerebrospinal fluid
      (CSF) leak (p = 0.0339) and a reduced incidence of neo-ostium closure (p =
      0.0001). Aspirin sensitivity and asthma were associated with a reduced incidence
      of reoperation (p <= 0.001) and increased symptom improvement (p < 0.005).
      Restenosis or closure of the frontal neo-ostium was associated with less symptom
      improvement (p < 0.04) but not with reoperation. CONCLUSION: The EMLP is an
      effective salvage procedure for refractory frontal sinusitis based on data from
      higher-volume centers.

PMID- 29210503
TI  - Efficient Yttrium(III) Chloride-Treated TiO2 Electron Transfer Layers for
      Performance-Improved and Hysteresis-Less Perovskite Solar Cells.
AB  - Hybrid organic-inorganic metal halide perovskite solar cells have attracted
      widespread attention, owing to their high performance, and have undergone rapid
      development. In perovskite solar cells, the charge transfer layer plays an
      important role for separating and transferring photogenerated carriers. In this
      work, an efficient YCl3 -treated TiO2 electron transfer layer (ETL) is used to
      fabricate perovskite solar cells with enhanced photovoltaic performance and less
      hysteresis. The YCl3 -treated TiO2 layers bring about an upward shift of the
      conduction band minimum (ECBM ), which results in a better energy level alignment
      for photogenerated electron transfer and extraction from the perovskite into the
      TiO2 layer. After optimization, perovskite solar cells based on the YCl3 -treated
      TiO2 layers achieve a maximum power conversion efficiency of about 19.99 % (19.29
      % at forward scan) and a steady-state power output of about 19.6 %. Steady-state
      and time-resolved photoluminescence measurements and impedance spectroscopy are
      carried out to investigate the charge transfer and recombination dynamics between
      the perovskite and the TiO2 electron transfer layer interface. The improved
      perovskite/TiO2 ETL interface with YCl3 treatment is found to separate and
      extract photogenerated charge rapidly and suppress recombination effectively,
      which leads to the improved performance.

PMID- 29210505
TI  - Pulmonary aspiration of sinus secretions in patients with cystic fibrosis.
AB  - BACKGROUND: Indirect evidence suggests that sinonasal secretions are aspirated
      into the lungs of patients with cystic fibrosis (CF), contributing to infection,
      subsequent tissue damage, and decreased lung function. Our objective is to
      determine whether sinonasal secretions are transferred to the lungs in patients
      with CF-related sinus disease and healthy subjects, particularly in the recumbent
      position and during sleep. METHODS: We performed a prospective, controlled trial
      to detect pulmonary aspiration of radiolabeled albumin applied to the nasal
      mucosa of study subjects with chronic sinusitis related to CF and control
      subjects without sinus disease. Radioactive counts were measured in the lungs and
      compared to background counts in both groups after 8 hours of rest/sleep.
      RESULTS: Complete data was collected on 12 CF patients and 6 controls. Eleven
      patients with CF demonstrated higher lung counts than background counts. The
      average counts of radiolabeled albumin in the lungs of CF patients were
      significantly greater than background counts (p = 0.03). Controls did not
      demonstrate this finding (p > 0.90), with only one-half demonstrating lung counts
      greater than background counts. CONCLUSION: This study provides direct evidence
      of aspiration of sinonasal secretions into the lungs of patients with CF and
      healthy adults in the recumbent position. The fact that both patients and
      controls aspirated secretions suggests that aspiration alone does not account for
      the pathogenesis of lung disease in CF patients.

PMID- 29210506
TI  - Generation of new glutinous rice by CRISPR/Cas9-targeted mutagenesis of the Waxy
      gene in elite rice varieties.
AB  - In rice, amylose content (AC) is controlled by a single dominant Waxy gene. We
      used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR
      associated 9 (Cas9) to introduce a loss-of-function mutation into the Waxy gene
      in two widely cultivated elite japonica varieties. Our results show that
      mutations in the Waxy gene reduce AC and convert the rice into glutinous ones
      without affecting other desirable agronomic traits, offering an effective and
      easy strategy to improve glutinosity in elite varieties. Importantly, we
      successfully removed the transgenes from the progeny. Our study provides an
      example of generating improved crops with potential for commercialization, by
      editing a gene of interest directly in elite crop varieties.

PMID- 29210508
TI  - Phelan-McDermid syndrome and cancer predisposition: The value of a karyotype.

PMID- 29210507
TI  - Acceptability of multiple micronutrient powders and iron syrup in Bihar, India.
AB  - Nearly two thirds of young children are anaemic in Bihar, India. Paediatric iron
      and folic acid syrup (IFAS) and multiple micronutrient powders (MNPs) are two
      evidence-based interventions to prevent anaemia. Using a randomized crossover
      design, we examined the acceptability of IFAS versus MNPs for children 6-23
      months. In a catchment area of 2 health centres in Bihar, health front-line
      workers (FLWs) delivered either (a) IFAS twice weekly or (b) MNPs for 1 month
      followed by the other supplementation strategy for 1 month to the same families
      (NCT02610881). Household surveys were conducted at baseline (N = 100), 1 month
      after receiving the first intervention (1 month; N = 95), and 1 month after the
      second intervention (2 months; N = 93). Focus group discussions (10 FLWs) and in
      depth interviews (20 mothers) were held at 1 and 2 months. We used chi-square and
      Fisher exact tests to test mothers' product preferences. Qualitative data were
      analysed using MaxQDA and Excel employing a thematic analysis approach. There was
      high adherence and acceptability for both products (>80%). There was no
      significant difference in preference (p < .05) on perceived benefits (39% MNPs,
      40% IFAS), side effects (30% MNPs, 30% IFAS), ease of use (42% IFAS, 31% MNPs),
      child preference (45% IFAS, 37% MNPs), and maternal preference (44% IFAS, 34%
      MNPs). Mothers and FLWs indicated that the direct administration of IFAS ensured
      that children consumed the full dose, and MNPs intake depended on the quantity of
      food consumed, especially among younger children, which emphasizes the need to
      integrate supplementation with the promotion of optimal child feeding practices.

PMID- 29210510
TI  - Glycosaminoglycan and Proteoglycan-Based Biomaterials: Current Trends and Future
      Perspectives.
AB  - Proteoglycans and their glycosaminoglycans (GAG) are essential for life as they
      are responsible for orchestrating many essential functions in development and
      tissue homeostasis, including biophysical properties and roles in cell signaling
      and extracellular matrix assembly. In an attempt to capture these biological
      functions, a range of biomaterials are designed to incorporate off-the-shelf
      GAGs, typically isolated from animal sources, for tissue engineering, drug
      delivery, and regenerative medicine applications. All GAGs, with the exception of
      hyaluronan, are present in the body covalently coupled to the protein core of
      proteoglycans, yet the incorporation of proteoglycans into biomaterials remains
      relatively unexplored. Proteoglycan-based biomaterials are more likely to
      recapitulate the unique, tissue-specific GAG profiles and native GAG presentation
      in human tissues. The protein core offers additional biological functionality,
      including cell, growth factor, and extracellular matrix binding domains, as well
      as sites for protein immobilization chemistries. Finally, proteoglycans can be
      recombinantly expressed in mammalian cells and thus offer genetic manipulation
      and metabolic engineering opportunities for control over the protein and GAG
      structures and functions. This Progress Report summarizes current developments in
      GAG-based biomaterials and presents emerging research and future opportunities
      for the development of biomaterials that incorporate GAGs presented in their
      native proteoglycan form.

PMID- 29210509
TI  - Arboviruses and their related infections in China: A comprehensive field and
      laboratory investigation over the last 3 decades.
AB  - Since the 1980s, a comprehensive field and laboratory investigation has been
      conducted throughout China, and a total of 29 virus species belonging to 7
      families and 13 genera were identified through virological, morphological, and
      immunological methods, as well as whole-genome sequencing and molecular genetic
      analyses. Most of the virus isolates belong to 9 genera in the families
      Flaviviridae, Bunyaviridae, Togaviridae, and Reoviridae. Among them, 4 genera
      (Orthobunyavirus, Bunyavirus, Phlebovirus, and Nairovirus) belong to the family
      Bunyaviridae and 3 genera (Seadonavirus, Orbivirus, and Cypovirus) belong to the
      family Reoviridae. Analyses of the relationships between viruses and human/animal
      diseases indicated that Japanese encephalitis virus, dengue virus, severe fever
      with thrombocytopenia syndrome virus, tick-borne encephalitis virus, Crimean
      Congo hemorrhagic fever virus, West Nile virus, and Tahyna virus can cause human
      and animal infections and disease epidemics in China. This review systematically
      introduces the current status of the diversity and geographical distribution of
      arboviruses and vectors in China. In addition, our results provide strong
      technical support for the prevention and control of arboviral diseases, the
      treatment of epidemics, and the early warning and prediction of diseases, and so
      they are significant for the control and prevention of arboviral diseases in Asia
      and around the world.

PMID- 29210511
TI  - Enhanced Fluorescence Properties of Stilbene-Containing Alternating Copolymers.
AB  - In recent years, nonconjugated, fluorophore-free organic polymers have emerged as
      potentially useful light-emitting materials. The fluorescence properties of a
      novel class of nonconjugated, tert-butyl carboxylate functionalized stilbene
      containing alternating copolymers are investigated in this work. These sterically
      crowded, semi-rigid copolymers exhibit very strong blue fluorescence in organic
      solvents upon irradiation. The origin of the fluorescent band with high quantum
      yield is attributed to the "through space" pi-pi interactions between the phenyl
      rings from the stilbene and C?O groups from the anhydride groups. To the best of
      our knowledge, the di-tert-butyl group-containing stilbene and maleic anhydride
      alternating copolymer showed one of the highest fluorescent intensities among all
      fluorophore-free polymers. The excellent linearity of the luminescence property
      of this copolymer is an important attribute for future potential quantitative
      applications. The fluorescence is maintained when the tert-butyl groups are
      removed and the resulting carboxylic acid-functionalized copolymer is dissolved
      in water at neutral pH, which can render these copolymers as attractive
      candidates for diagnostic and therapeutic applications.

PMID- 29210512
TI  - Auditory evoked potentials in children and adolescents with Down syndrome.
AB  - Down syndrome, or trisomy 21, is the most common genetic alteration in humans.
      The syndrome presents with several features, including hearing loss and changes
      in the central nervous system, which may affect language development in children
      and lead to school difficulties. The present study aimed to investigate group
      differences in the central auditory system by long-latency auditory evoked
      potentials and cognitive potential. An assessment of 23 children and adolescents
      with Down syndrome was performed, and a control group composed of 43 children and
      adolescents without genetic and/or neurological changes was used for comparison.
      All children underwent evaluation with pure tone and vocal audiometry, acoustic
      immitance measures, long-latency auditory evoked potentials, and cognitive
      potential. Longer latencies of the waves were found in the Down syndrome group
      than the control group, without significant differences in amplitude, suggesting
      that individuals with Down syndrome have difficulty in discrimination and
      auditory memory. It is, therefore, important to stimulate and monitor these
      children in order to enable adequate development and improve their life quality.
      We also emphasize the importance of the application of auditory evoked potentials
      in clinical practice, in order to contribute to the early diagnosis of hearing
      alterations and the development of more research in this area.

PMID- 29210513
TI  - The efficacy of a novel budesonide chitosan gel on wound healing following
      endoscopic sinus surgery.
AB  - BACKGROUND: Adhesion formation and ostial stenosis are common causes of surgical
      failure after endoscopic sinus surgery (ESS). Postoperative topical steroid
      application has been shown to improve wound healing. Chitosan-dextran gel (CD
      gel) is an effective hemostatic nasal dressing. This study aims to determine the
      effect of the addition of budesonide to CD gel on postoperative ostial stenosis
      and adhesion formation following ESS. METHODS: This prospective, blinded,
      randomized controlled trial was conducted between October 2012 and April 2015.
      Thirty-six patients over 18 years undergoing ESS were randomized to receive
      either: no treatment, CD gel, CD gel with 1 mg/ 2 mL budesonide, or topical
      steroid cream to their left or right sinuses (different treatment each side).
      Each sinus ostium and endoscopic features of wound healing was measured
      intraoperation, and 2 weeks, 3 months, and 12 months postoperation. RESULTS: Data
      was analyzed using the analysis of variance (ANOVA) and post hoc Tukey honestly
      significant difference (HSD) tests. There was a significant reduction in stenosis
      within all 3 sinuses ostia sites when CD + budesonide was compared to control,
      with the greatest effect seen at 12 months: The mean +/- standard deviation (SD)
      percentage of baseline areas at 12 months were 76% +/- 6.2% vs 37% +/- 23.5%, 76%
      +/- 6.3% vs 52% +/- 4.9%, and 83% +/- 6.5% vs 58% +/- 5.0% (all p < 0.05), for CD
      + budesonide compared to control in the frontal, sphenoid, and maxillary sinuses,
      respectively. The incidence of adhesions was 4% in the CD + budesonide group
      compared to 15% in the control group. CONCLUSION: This study has shown that CD
      gel, when combined with topical budesonide solution, improves long-term sinus
      ostial patency and prevents ostial stenosis post-ESS.

PMID- 29210514
TI  - 30 s Response Time of K+ Ion-Selective Hydrogels Functionalized with 18-Crown-6
      Ether Based on QCM Sensor.
AB  - Potassium detection is critical in monitoring imbalances in electrolytes and
      physiological status. The development of rapid and robust potassium sensors is
      desirable in clinical chemistry and point-of-care applications. In this study,
      composite supramolecular hydrogels are investigated: polyethylene glycol
      methacrylate and acrylamide copolymer (P(PEGMA-co-AM)) are functionalized with 18
      crown-6 ether by employing surface initiated polymerization. Real-time potassium
      ion monitoring is realized by combining these compounds with quartz crystal
      microbalance. The device demonstrates a rapid response time of ~30 s and a
      concentration detection range from 0.5 to 7.0 * 10-3 m. These hydrogels also
      exhibit high reusability and K+ ion selectivity relative to other cations in
      biofluids such as Na+ , NH4+ , Mg2+ , and Ca2+ . These results provide a new
      approach for sensing alkali metal ions using P(PEGMA-co-AM) hydrogels.

PMID- 29210515
TI  - Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis
      type II: Data from the Hunter Outcome Survey (HOS).
AB  - Several cases of phenotypic variability among family members with
      mucopolysaccharidosis type II (MPS II) have been reported, but the data are
      limited. Data from patients enrolled in the Hunter Outcome Survey (HOS) were used
      to investigate intrafamilial variability in male siblings with MPS II. As of July
      2015, data were available for 78 patients aged >=5 years at last visit who had at
      least one affected sibling (39 sibling pairs). These patients were followed
      prospectively (i.e., they were alive at enrollment in HOS). The median age at the
      onset of signs and symptoms was the same for the elder and younger brothers (2.0
      years); however, the younger brothers were typically diagnosed at a younger age
      than the elder brothers (median age, 2.5 and 5.1 years, respectively). Of the 39
      pairs, eight pairs were classified as being discordant (the status of four or
      more signs and symptoms differed between the siblings); 21 pairs had one, two, or
      three signs and symptoms that differed between the siblings, and 10 pairs had
      none. Regression status of the majority of the developmental milestones studied
      was generally concordant among siblings. Functional classification, a measure of
      central nervous system involvement, was the same in 24/28 pairs, although four
      pairs were considered discordant as functional classification differed between
      the siblings. Overall, this analysis revealed similarity in the clinical
      manifestations of MPS II among siblings. This information should help to improve
      our understanding of the clinical presentation of the disease, including
      phenotype prediction in affected family members.

PMID- 29210517
TI  - The current status of cognitive behavioral therapy for eating disorders: Marking
      the 51st Annual Convention of the Association of Behavioral and Cognitive
      Therapies.

PMID- 29210516
TI  - Efficacy and Cost-Effectiveness Analysis of Evidence-Based Nursing Interventions
      to Maintain Tissue Integrity to Prevent Pressure Ulcers and Incontinence
      Associated Dermatitis.
AB  - BACKGROUND: A reduction in tissue tolerance promotes the development of pressure
      ulcers (PUs) and incontinence-associated dermatitis (IAD). AIMS: To determine the
      cost-effectiveness and efficacy of evidence-based (EB) nursing interventions on
      increasing tissue tolerance by maintaining tissue integrity. METHODS: The study
      involved 154 patients in two intensive care units (77 patients, control group; 77
      patients, intervention group). Data were collected using the following: patient
      characteristics form, Braden PU risk assessment scale, tissue integrity
      monitoring form, PU identification form, IAD and severity scale, and a cost table
      of the interventions. Patients in the intervention group were cared for by nurses
      trained in the use of the data collection tools and in EB practices to improve
      tissue tolerance. Routine nursing care was given to the patients in the control
      group. The researcher observed all patients in terms of tissue integrity and
      recorded the care-related costs. RESULTS: Deterioration of tissue integrity was
      observed in 18.2% patients in the intervention group compared to 54.5% in the
      control group (p < .05). The average cost to increase tissue tolerance prevention
      in the intervention and control groups was X- = $204.34 +/- 41.07 and X- =
      $138.90 +/- 1.70, respectively. LINKING EVIDENCE TO ACTION: It is recommended
      that EB policies and procedures are developed to improve tissue tolerance by
      maintaining tissue integrity. CONCLUSIONS: Although the cost of EB preventive
      initiatives is relatively high compared to those that are not EB, the former
      provide a significant reduction in the prevalence of tissue integrity
      deterioration.

PMID- 29210518
TI  - Body image and eating behavior in young adults born preterm.

PMID- 29210519
TI  - Air pollutants may be environmental risk factors in chronic rhinosinusitis
      disease progression.
AB  - BACKGROUND: Little is known about the role of environmental exposures in the
      pathophysiology of chronic rhinosinusitis (CRS). In this study, we measured the
      impact of air pollutants (particulate matter 2.5 [PM2.5 ] and black carbon [BC])
      on CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP).
      METHODS: Spatial modeling from pollutant monitoring sites was used to estimate
      exposures surrounding residences for patients meeting inclusion criteria (total
      patients, n = 234; CRSsNP, n = 96; CRSwNP, n = 138). Disease severity outcome
      measures included modified Lund-Mackay score (LMS), systemic steroids, number of
      functional endoscopic sinus surgeries (FESS), and 22-item Sino-Nasal Outcome Test
      (SNOT-22) score. PM2.5 and BC exposures were correlated with outcome measures.
      RESULTS: Mean PM2.5 and BC findings were not significantly different between
      CRSwNP and CRSsNP patients or patients with and without asthma. Among those with
      CRSsNP, PM2.5 was significantly associated with undergoing FESS. For each unit
      increase in PM2.5 , there was a 1.89-fold increased risk in the proportion of
      CRSsNP patients who required further surgery (p = 0.015). This association was
      not identified in CRSwNP patients (p = 0.445). BC was also significantly
      associated with SNOT-22 score in the CRSsNP group. For each 0.1-unit increase in
      BC, there was a 7.97-unit increase in SNOT-22 (p = 0.008). A similar, although
      not significant, increase in SNOT-22 was found with increasing BC in the CRSwNP
      group (p = 0.728). CONCLUSION: Air pollutants correlate with CRS symptom severity
      that may be influenced by exposure levels, with a more pronounced impact on
      CRSsNP patients. This study is the first to demonstrate the possible role of
      inhalant pollutants in CRS phenotypes, addressing a critical knowledge gap in
      environmental risk factors for disease progression.

PMID- 29210520
TI  - Supplementation during pregnancy with small-quantity lipid-based nutrient
      supplements or multiple micronutrients, compared with iron and folic acid,
      increases women's urinary iodine concentration in semiurban Ghana: A randomized
      controlled trial.
AB  - There is little information on whether prenatal multiple micronutrient (MMN)
      supplements containing iodine affect women's iodine status. In the International
      Lipid-based Nutrient Supplements DYAD-Ghana trial, we aimed to assess women's
      urinary iodine concentration (UIC, MUg/L) during pregnancy, as one of the planned
      secondary outcomes. Women (n = 1,320) <20 weeks of gestation were randomized to
      consume 60 mg iron and 400 MUg folic acid per day (iron and folic acid [IFA]); 18
      vitamins and minerals including 250 MUg iodine per day (MMN); or 20 g/day of
      small-quantity lipid-based nutrient supplements (LNS) with the same and
      additional 4 vitamins and minerals as the MMN (LNS). In a subsample (n = 295), we
      tested differences in groups' geometric mean UICs at 36 weeks of gestation
      controlling for baseline UIC and compared the geometric means (approximately
      median UICs) with the World Health Organization (WHO) cut-offs: median UIC <150,
      150-249, and >=500 reflecting low, adequate, and excessive iodine intakes,
      respectively. At baseline, overall median UIC was 137. At 36 weeks of gestation,
      controlling for baseline UIC, geometric mean (95% confidence interval) UICs of
      the MMN (161 [133, 184]) and LNS (158 [132, 185]) groups did not differ; both
      values were significantly greater (overall p = .004) than that of the IFA group
      (116 [101, 135]). The median UICs of the MMN and LNS groups were within the WHO
      "adequate" range, whereas that of the IFA group was below the WHO adequate range.
      In this setting, supplementation during pregnancy with small-quantity LNS or MMN
      providing iodine at the WHO-recommended dose, compared with IFA, increases the
      likelihood of adequate iodine status.

PMID- 29210521
TI  - Regulatory Efficacy of Brown Seaweed Lessonia nigrescens Extract on the Gene
      Expression Profile and Intestinal Microflora in Type 2 Diabetic Mice.
AB  - SCOPE: In this study, the antidiabetic activity of Lessonia nigrescens ethanolic
      extract (LNE) is investigated in streptozotocin (SZT)-induced type 2 diabetic
      mice fed with a high-sucrose/high-fat diet. METHODS AND RESULTS: Ultra high
      performance liquid chromatography coupled with photo-DAD and electospray
      ionization-mass spectrometry (ESI-MS) is employed to analyze the major compounds
      in LNE. The components of the intestinal microflora in type 2 diabetic mice are
      analyzed by high-throughput next-generation 16S rRNA gene sequencing. Fasting
      blood glucose levels in diabetic mice are significantly decreased after LNE
      administration. The histology reveals that LNE could protect the cellular
      architecture of liver and kidney. LNE treatment significantly increases
      Bacteroidetes and decreases Firmicutes populations in intestinal microflora.
      Specifically, It could selectively enrich the amounts of beneficial bacteria,
      Barnesiella, as well as reduce the abundances of Clostridium and Alistipes. The
      increased gene and protein expression levels of phosphatidylinositol 3-kinase
      (PI3K) in the liver are observed in LNE treatment groups, while the expressions
      of c-Jun N-terminal kinase (JNK) are significantly downregulated. CONCLUSION: The
      above findings suggest that LNE could be considered as a functional food for
      reducing blood glucose and regulating intestinal microflora.

PMID- 29210523
TI  - Activities of 11-Azaartemisinin and N-Sulfonyl Derivatives against Neospora
      caninum and Comparative Cytotoxicities.
AB  - Neosporosis caused by the apicomplexan parasite Neospora caninum is an
      economically important disease that induces abortion in dairy and beef cattle.
      There are no vaccines or drugs available on the market for control or treatment
      of the disease in bovines. The peroxide artemisinin and its derivatives used
      clinically for treatment of malaria are active against N. caninum and other
      apicomplexan parasites. We have now evaluated the activities of the readily
      accessible and chemically robust 11-azaartemisinin 5 and selected N-sulfonyl
      derivatives prepared as described in the accompanying paper against N. caninum
      tachyzoites grown in infected human foreskin fibroblasts. Azaartemisinin elicited
      an IC50 value of 150 nm, and the 2',5'-dichloro-3'-thienylsulfonyl-11
      azaartemisinin 17 was found to be the most active, with an IC50 value of 40 nm.
      Comparison with normal human fetal lung fibroblasts HFLF WI-38 revealed
      relatively benign cytotoxicity. The compounds were also screened in vitro against
      TK-10 (renal), UACC-62 (melanoma) and MCF-7 (breast) cancer cell lines; overall,
      in line with activities against HFLF cells, most compounds in the series were
      found to be inactive.

PMID- 29210525
TI  - Digitized Speech Characteristics in Patients with Maxillectomy Defects.
AB  - PURPOSE: Accurate evaluation of speech characteristics through formant frequency
      measurement is important for proper speech rehabilitation in patients after
      maxillectomy. This study aimed to evaluate the utility of digital acoustic
      analysis and vowel pentagon space for the prediction of speech ability after
      maxillectomy, by comparing the acoustic characteristics of vowel articulation in
      three classes of maxillectomy defects. MATERIALS AND METHODS: Aramany's
      classifications I, II, and IV were used to group 27 male patients after
      maxillectomy. Digital acoustic analysis of five Japanese vowels-/a/, /e/, /i/,
      /o/, and /u/-was performed using a speech analysis system. First formant (F1) and
      second formant (F2) frequencies were calculated using an autocorrelation method.
      Data were plotted on an F1-F2 plane for each patient, and the F1 and F2 ranges
      were calculated. The vowel pentagon spaces were also determined. One-way ANOVA
      was applied to compare all results between the three groups. RESULTS: Class II
      maxillectomy patients had a significantly higher F2 range than did Class I and
      Class IV patients (p = 0.002). In contrast, there was no significant difference
      in the F1 range between the three classes. The vowel pentagon spaces were
      significantly larger in class II maxillectomy patients than in Class I and Class
      IV patients (p = 0.014). CONCLUSION: The results of this study indicate that the
      acoustic characteristics of maxillectomy patients are affected by the defect
      area. This finding may provide information for obturator design based on vowel
      articulation and defect class.

PMID- 29210522
TI  - Emerging Roles of Electrospun Nanofibers in Cancer Research.
AB  - This article reviews the recent progress of electrospun nanofibers in cancer
      research. It begins with a brief introduction to the emerging potential of
      electrospun nanofibers in cancer research. Next, a number of recent advances on
      the important features of electrospun nanofibers critical for cancer research are
      discussed including the incorporation of drugs, control of release kinetics,
      orientation and alignment of nanofibers, and the fabrication of 3D nanofiber
      scaffolds. This article further highlights the applications of electrospun
      nanofibers in several areas of cancer research including local chemotherapy,
      combinatorial therapy, cancer detection, cancer cell capture, regulation of
      cancer cell behavior, construction of in vitro 3D cancer model, and engineering
      of bone microenvironment for cancer metastasis. This progress report concludes
      with remarks on the challenges and future directions for design, fabrication, and
      application of electrospun nanofibers in cancer diagnostics and therapeutics.

PMID- 29210524
TI  - TSC1 enables plastid development under dark conditions, contributing to rice
      adaptation to transplantation shock.
AB  - Since its domestication from wild rice thousands of years ago, rice has been
      cultivated largely through transplantation. During transplantation from the
      nursery to the paddy field, rice seedlings experience transplantation shock which
      affects their physiology and production. However, the mechanisms underlying
      transplantation shock and rice adaptation to this shock are largely unknown.
      Here, we isolated a transplant-sensitive chloroplast-deficient (tsc1) rice mutant
      that produces albino leaves after transplantation. Blocking light from reaching
      the juvenile leaves and leaf primordia caused chloroplast deficiencies in
      transplanted tsc1 seedlings. TSC1 encodes a noncanonical adenosine triphosphate
      binding cassette (ABC) transporter homologous to AtNAP14 and is of cyanobacterial
      origin. We demonstrate that TSC1 controls plastid development in rice under dark
      conditions, and functions independently of light signaling. However, light
      rescued the tsc1 mutant phenotype in a spectrum-independent manner. TSC1 was
      upregulated following transplantation, and modulated the iron and copper levels,
      thereby regulating prolamellar body formation during the early P4 stage of leaf
      development. Therefore, TSC1 is indispensable for plastid development in the
      absence of light, and contributes to adaptation to transplantation shock. Our
      study provides insight into the regulation of plastid development and establishes
      a framework for improving recovery from transplantation shock in rice.

PMID- 29210526
TI  - Understanding the Impact of Film Disorder and Local Surface Potential in
      Ultraviolet Photoelectron Spectroscopy of PEDOT.
AB  - The spectra of conducting polymers obtained using ultraviolet photoelectron
      spectroscopy (UPS) exhibit a typical broadening of the tail sigmaUPS ~ 1 eV,
      which by an order of magnitude exceeds a commonly accepted value of the
      broadening of the tail of the density of states sigmaDOS ~ 0.1 eV obtained using
      transport measurements. In this work, an origin of this anomalous broadening of
      the tail of the UPS spectra in a doped conducting polymer, PEDOT (poly(3,4
      ethylenedioxythiophene)), is discussed. Based on the semiempirical approach and
      using a realistic morphological model, the density of valence states in PEDOT
      doped with molecular counterions is computed. It is shown that due to a
      disordered character of the material with randomly distributed counterions, the
      localized charge carriers in PEDOT crystallites experience spatially varying
      electrostatic potential. This leads to spatially varying local vacuum levels and
      binding energies. Taking this variation into account the UPS spectrum is obtained
      with the broadening of the tail comparable to the experimentally observed one.
      The results imply that the observed broadening of the tail of the UPS spectra in
      PEDOT provides information about a disordered spatially varying potential in the
      material rather than the broadening of the DOS itself.

PMID- 29210527
TI  - Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A
      population-based study.
AB  - BACKGROUND: Helicobacter pylori is an important etiologic factor for peptic
      ulcers and gastric cancer, one of the top ten leading causes of cancer death in
      Puerto Rico. However, the prevalence of H. pylori infections in this population
      was previously unknown. The aim of this study was to examine the seroprevalence
      of H. pylori and its associated risk factors in Puerto Rico. MATERIALS AND
      METHODS: A cross-sectional study was designed using an existing population-based
      biorepository. Seropositivity was determined using the PremierTM H. pylori
      immunoassay. Helicobacter pylori seroprevalence was estimated with 95% confidence
      using marginal standardization following logistic regression. To assess the risk
      factors associated with H. pylori seropositivity, a multivariable log-binomial
      model was fitted to estimate the prevalence ratio (PR) and its 95% confidence
      interval (95% CI). RESULTS: A total of 528 population-based serum samples were
      analyzed. The mean age of the study population was 41 +/- 12 years, of whom 55.3%
      were females. The overall seroprevalence of H. pylori was 33.0% (95% CI = 28.3%
      38.1%). Increasing age and having <12 years of education were significantly (P <
      .05) associated with H. pylori seropositivity in the multivariable model;
      however, residing in counties with low population density reached marginal
      significance (P = .085). CONCLUSIONS: We report that H. pylori infection is
      common among Hispanics living in Puerto Rico. The H. pylori seroprevalence
      observed in Puerto Rico is similar to the seroprevalence reported in the overall
      population of the United States. The association between H. pylori seroprevalence
      and the risk factors analyzed offers insight into the epidemiology of gastric
      cancer in Puerto Rico and warrants further investigation.

PMID- 29210532
TI  - A Comprehensive Structural Overview of p38alpha Mitogen-Activated Protein Kinase
      in Complex with ATP-Site and Non-ATP-Site Binders.
AB  - Herein we review all the currently available ATP-site and non-ATP-site ligands
      bound to p38alpha mitogen-activated protein kinase (MAPK) available in the RCSB
      Protein Data Bank (PDB). The co-crystallized inhibitors have been classified into
      different families according to their experimental binding mode and chemical
      structure, and the ligand-protein interactions are discussed using the most
      representative compounds. This systematic structural analysis could provide some
      take-home lessons for drug discovery programs aimed at the rational
      identification and optimization of new p38alpha MAPK inhibitors.

PMID- 29210531
TI  - Comparison of endoscopic and open resection of sinonasal squamous cell carcinoma:
      a propensity score-matched analysis of 652 patients.
AB  - BACKGROUND: The use of endoscopic resection as an alternative to open surgery for
      sinonasal malignancies has increased in the past 20 years. METHODS: The National
      Cancer Database was queried for cases of sinonasal squamous cell carcinoma
      (SNSCC) without cervical or distant metastases that were treated surgically
      between 2010 and 2014. They were split into 2 groups based on surgical approach:
      open or endoscopic. Demographics, facility and insurance type, stage, tumor
      characteristics, postoperative treatment, 30-day readmission rate, 30- and 90-day
      mortality, and overall survival (OS) were compared between the 2 groups. Cox
      proportional hazard analysis was performed. Propensity score matching (PSM) was
      used to mimic a randomized, controlled trial. RESULTS: A total of 1,483 patients
      were identified: 353 (23.8%) received endoscopic and 1130 (76.2%) received open
      surgery. Age, gender, race, geographic region, tumor size, surgical margins,
      postoperative chemoradiation, and 30-day readmissions did not vary significantly
      between the 2 groups. Open surgery was more common in academic centers (62.8% vs
      54.2%; p = 0.004), less common for tumors of the ethmoid and sphenoid sinus (p <
      0.0001), less common for stage IVB tumors, and associated with longer hospital
      stay (mean, 4.67 days vs 2.50 days; p < 0.0001). Five-year OS (5Y-OS) was not
      significantly different between the 2 approaches (p = 0.953; open: 5Y-OS, 56.5%;
      95% confidence interval, 51.3% to 61.6%; endoscopic: 5Y-OS, 46.0%; 95% confidence
      interval, 33.2% to 58.8%). In the PSM cohort of 652 patients, there was also no
      significant difference in OS (p = 0.850). CONCLUSION: Endoscopic surgery is an
      effective alternative to open surgery, even after accounting for confounding
      factors that may favor its use over the open approach. It is also associated with
      a shorter hospital stay.

PMID- 29210533
TI  - Rapid Differential Diagnosis of Breast Microcalcification Using Targeted Near
      Infrared Fluorophores.
AB  - Early detection and differential diagnosis of breast microcalcifications are of
      significant importance in effective treatment of early breast cancer, because
      mineral composition of breast calcification is directly associated with different
      pathological states. However, applying image-based modalities for component
      identification in breast calcification remains challenging, because no
      calcification-specific contrast agent is available to distinguish between benign
      and malignant (type I and type II, respectively) calcifications of breast
      lesions. In this study, real-time near-infrared (NIR) fluorescence imaging of
      breast microcalcifications using targeted NIR fluorophores in combination with
      dual-channel NIR fluorescence imaging system is reported. This strategy can be
      used to solve major problem in mammography and ultrasonography methods for the
      differentiation of benign and malignant microcalcifications. Thus, this novel
      technology shows significant potential for breast cancer diagnosis and image
      guided surgery performed with increased precision and efficiency by providing
      differential diagnosis of breast microcalcifications.

PMID- 29210534
TI  - Antiepileptic drugs for the primary and secondary prevention of seizures in viral
      encephalitis.
AB  - STATEMENT: The mission of the Cochrane Nursing Care Field (CNCF) is to improve
      health outcomes through increasing the use of the Cochrane Library and supporting
      Cochrane's role by providing an evidence base for nurses and healthcare
      professionals who deliver, lead or research nursing care. The CNCF produces
      Cochrane Corner columns, summaries of recent nursing-care-relevant Cochrane
      Reviews that are regularly published in collaborating nursing-related journals.
      Information on the processes CNCF has developed can be accessed at:
      cncf.cochrane.org/evidence-transfer-program-review-summaries. This is a Cochrane
      review summary of: Pandey S, Rathore C, Michael D ( 2016 ) Antiepileptic drugs
      for the primary and secondary prevention of seizures in viral encephalitis.
      Cochrane Database of Systematic Reviews. Issue 5. CD010247. doi:
      10.1002/14651858.CD010247.pub3.

PMID- 29210535
TI  - Assessment, care and management of patients with red eye.
AB  - Red eye is a common ocular presentation in primary care, and there are several
      challenges that healthcare practitioners may encounter when caring for such
      patients. The main ocular conditions that can give rise to red eye are: primary
      acute angle closure glaucoma, acute iritis, dry eye, blepharitis and
      conjunctivitis. Red eye can be classified as sight-threatening or non-sight
      threatening. Many patients presenting with painless red eye and normal vision
      usually recover well. However, when red eye is associated with pain, photophobia,
      watering and blurred vision, it is potentially sight-threatening and must be
      addressed urgently. Therefore, it is vital for healthcare practitioners to be
      able to undertake a careful assessment of the patient and make an accurate
      diagnosis early. This article provides an overview of the common causes of red
      eye encountered in general practice or an eye clinic. It discusses the nurse's
      role in the care and management of patients with red eye, with reference to
      patient assessment, the skills required to make an accurate diagnosis, treatment
      and health promotion.

PMID- 29210536
TI  - HIV and AIDS: An overview of the current issues, treatment and prevention.
AB  - The theme of World AIDS Day 2017 is 'let's end it'. After almost 40 years since
      the first occurrences of human immunodeficiency virus (HIV), it is possible to
      envision an end to the HIV epidemic, one of the most serious health and
      development challenges humanity has faced. This article provides an overview of
      the current approaches to the treatment, care and support of people living with
      HIV and acquired immune deficiency syndrome (AIDS). It also discusses the
      challenges associated with HIV and AIDS that remain, HIV prevention strategies,
      and the nurse's role in caring for people living with HIV. It outlines the
      Australian partnership approach to HIV, which provides a background for
      reflection on the response to HIV and AIDS in the UK and worldwide.

PMID- 29210537
TI  - Secular Trends and Current Challenges of Lifestyle Diseases : The Hisayama Study.

PMID- 29210538
TI  - Neuraminidase Amino Acid Sequences of Influenza A/H3N2 and B Viruses Isolated
      from Influenza Patients in the 2014/15 Japanese Influenza Season.
AB  - Background: Neuraminidase (NA) is a surface protein essential for influenza virus
      replication. NA inhibitors are commonly used for the treatment of influenza
      patients in Japan. Several mutations that reduce the effect of NA inhibitors have
      been reported. We sequenced the whole NA segment of isolated virus from influenza
      patients and investigated the relation between the NA amino acid sequence and the
      50% inhibitory concentration (IC_50) of four NA inhibitors. Materials and
      Methods: Forty A/H3N2 and 19 B influenza virus isolated from patients in the
      2014/15 influenza season were analyzed. The IC_50 was determined by a
      neuraminidase inhibition assay using a fluorescent substrate. Viral RNA was
      amplified by RT-PCR and the genome was sequenced using a next generation
      sequencer. The deduced amino acid sequences were analyzed. Results: There was no
      AA change in the NA catalytic site of the A/H3N2 and B viruses isolated in the
      2014-15 influenza season. There was no significant relation between the NA amino
      acids and the IC_50 of the four NA inhibitors for A/H3N2 or B viruses.
      Conclusion: The catalytic site of NA was highly conserved for these A/H3N2 and B
      viruses. No emergence of NA amino acid mutations related to the sensitivity of
      the four currently used NA inhibitors was observed.

PMID- 29210539
TI  - Current Status and Future Perspective of Tolerance Induction in Patients with
      Kidney Transplantation.

PMID- 29210540
TI  - Endoscopic Submucosal Dissection is Feasible for Very Elderly Patients with Early
      Gastric Cancer : Comparison of Short-Term and Long-Term Outcomes in Very Elderly
      and Non-Elderly Patients.
AB  - Background/Aims: Endoscopic submucosal dissection (ESD) has become a standard
      procedure for the resection of early gastric cancer (EGC). However, the
      feasibility of ESD for very elderly patients, aged >= 80 years, has not been
      determined. Methodology: The study population included 67 non-elderly (NE)
      patients aged <= 65 years (80 lesions) and 22 very elderly (VE) patients >= 80
      years (26 lesions) with EGC who underwent ESD and met the criteria for absolute
      or expanded indications. Eighteen patients (18 lesions) who underwent ESD but did
      not meet the criteria for absolute and expanded indications were defined as the
      outside the indications (OI) group. Results: En bloc and complete resection rates
      were excellent in both the VE and NE groups, without differing significantly.
      Although the rates of ischemic heart disease and antithrombotic agent use were
      higher in the VE than in the NE group, procedure-related complication rates did
      not differ significantly. Of the seven very elderly patients in the OI group, two
      underwent additional gastrectomy, and the other five were followed-up without
      surgery. No patient in any group experienced local recurrence, metastasis or
      disease-specific death. Conclusions: Short- and long-term outcomes of ESD for VE
      patients with EGC were favorable and did not differ significantly from outcomes
      in NE patients. ESD may therefore be a good therapeutic option for both VE and NE
      patients with EGC.

PMID- 29210541
TI  - Coexistence of Reticulate Acropigmentation of Kitamura and Dowling-Degos Disease.

PMID- 29210542
TI  - Regulation of Viral Infection and Type 1 Diabetes ; Future Perspective.

PMID- 29210544
TI  - It's In the Bag! Appreciating proper BVM ventilation.

PMID- 29210543
TI  - Living Donor Liver Transplantation in an Elderly Recipient with Preserved
      Performance Status : A Case Report.
AB  - Background: Living donor liver transplantation (LDLT) in an elderly recipient is
      controversial. Case presentation: We report a case of LDLT in a 74-year-old
      female who had decompensated liver cirrhosis and hepatocellular carcinoma (HCC).
      She was the oldest recipient who received LDLT in Japan ever. She was rejected
      for LDLT at a nearby hospital because of her age.We decided to perform LDLT
      because her general condition was good (the Eastern Cooperative Oncology Group
      (ECOG) performance status 2 ). The surgery was uncomplicated and the
      postoperative course was uneventful, and the patient was discharged 35 days after
      the surgery. Currently she is living at home, and she has maintained a good
      quality of life. Conclusions: We believe that a recipient in good general
      condition is capable of undergoing LDLT despite advanced age.

PMID- 29210545
TI  - Letters: In Your Own Words. Shock.

PMID- 29210547
TI  - Police Transports: MCI plans should consider alternatives to EMS transport.

PMID- 29210546
TI  - NAEMSE Position Paper: Revised Standards and Guidelines on the Accreditation of
      Educational Programs.

PMID- 29210548
TI  - Are They Sick Enough? Analyzing the threshold for ALS response.

PMID- 29210549
TI  - Just a Cough? Examining when airway discomfort indicates something serious.

PMID- 29210551
TI  - Pediatric Pain: Evaluating prehospital opioid pain management in children.

PMID- 29210550
TI  - Blood Clot Breakdown. Should tPA be used to treat refractory v fib or other OHCA?

PMID- 29210552
TI  - Breastfeeding policy: The foundation for improving Australia's health.

PMID- 29210553
TI  - Improving Patient Safety: Foreword.

PMID- 29210554
TI  - Improving Patient Safety: Common Outpatient Medical Errors.
AB  - Medical errors are common and can lead to patient harm and death. Most research
      on errors has focused on inpatient care, yet errors are at least as common in the
      outpatient setting and likely are underreported. Common types of errors in the
      outpatient setting are diagnostic, drug, and testing errors. The most effective
      specific interventions for reducing errors in the outpatient setting remain
      unknown. Considering the current lack of data, the authors recommend a quality
      improvement approach to understanding local factors in patient safety.
      Appropriate education and training of all staff members in their roles in patient
      safety is an important aspect of any program to reduce errors, though these
      measures rarely are sufficient on their own. Creation of a culture of safety, use
      of adequate systems and policies for reporting and identifying errors, and use of
      technologies to prevent errors also are important.

PMID- 29210555
TI  - Improving Patient Safety: Care Transitions.
AB  - Care transitions are times of high risk of harm to patients. The transition from
      hospital care to outpatient care is perhaps the most well-studied transition and
      is encountered commonly in the family medicine setting. For discharge
      transitions, several hospital-based interventions for patients with major
      diagnoses have resulted in improvements in readmission rates, costs, and patient
      satisfaction. Prompt scheduling of a follow-up appointment with patients after
      discharge is crucial. Key issues to consider in the first post-discharge
      appointment include drug reconciliation and follow-up of any pending tests and
      results. In the outpatient setting, establishing working relationships with
      hospital physicians and consultants, educating patients to notify physicians of
      admissions to hospitals or other care facilities, and educating patients to bring
      current drug lists to appointments can improve care transitions. Physicians now
      can receive greater reimbursement for transitional care management services using
      new CPT codes.

PMID- 29210556
TI  - Improving Patient Safety: Prevention of Hospital Readmission.
AB  - Identifying and preventing avoidable hospital admissions have become cornerstone
      quality metrics that influence reimbursement and provision of quality care. Many
      initiatives focus on improving communication with other clinicians and patients,
      coordinating care after discharge, and improving care quality during the initial
      admission to prevent future readmissions. The Centers for Medicare and Medicaid
      Services define a readmission as an admission to any acute care hospital for any
      reason within 30 days of discharge from an acute care hospital. Certain risk
      factors can indicate the need for targeted intervention to prevent readmission.
      Several risk stratification screening tools have been developed to assist
      clinicians in identifying at-risk patients for early intervention. However, the
      evidence supporting the accuracy and reliability of these tools remains limited.

PMID- 29210557
TI  - Improving Patient Safety: Improving Communication.
AB  - Communication among physicians, staff, and patients is a critical element in
      patient safety. Effective communication skills can be taught and improved through
      training and awareness. The practice of family medicine allows for long-term
      relationships with patients, which affords opportunities for ongoing, high
      quality communication. There are many barriers to effective communication,
      including patient factors, clinician factors, and system factors, but tools and
      strategies exist to address these barriers, improve communication, and engage
      patients in their care. Use of universal precautions for health literacy,
      appropriate medical interpreters, and shared decision-making are evidence-based
      tools that improve communication and increase patient safety.

PMID- 29210558
TI  - Microphase Diffusion-Controlled Interfacial Polymerization for an Ultrahigh
      Permeability Nanofiltration Membrane.
AB  - The key to improving nanofiltration membrane permeance is reducing its thickness
      while maintaining high rejection. Herein, a 25 nm thick ultrathin polyamide layer
      was prepared by a microphase diffusion-controlled interfacial polymerization (MDC
      IP) of poly(ethyleneimine) and trimesoyl chloride, which is much thinner than the
      conventional interfacial polymerization (CIP) polyamide layer. A new formation
      mechanism for such an ultrathin layer is presented, which included a microphase
      interfacial reaction and eliminated loose layers due to the confinement of
      microphase diffusion and the termination of stepwise diffusion. Moreover, the
      polyamide layer was post-cross-linked to form a stable dual-cross-linked
      interwoven structure. Such a membrane showed an ultrahigh permeance of 1246
      kg/(m2 h MPa), which was 23 times that of CIP membranes. MDC-IP could efficiently
      control the microinterface between two immiscible phases, which provided a facile
      way to regulate the membrane at nanoscale.

PMID- 29210559
TI  - Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence
      Imaging, and Magnetic Resonance Imaging.
AB  - In this paper, we report synthesis and characterization of a novel multimodality
      (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer
      was derived from poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and integrated
      with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd-DOTA
      complex). The polymer was characterized using UV-vis absorption
      spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance
      imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and
      cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell
      lines shows the polymer's ability to be internalized in the cells. The transverse
      relaxation time (T2) of the polymer was observed to be pH-dependent, whereas the
      spin-lattice relaxation time (T1) was not. The pH probe in the polymer shows a
      strong fluorescence-based ratiometric pH response with emission window changes,
      exhibiting blue emission under acidic conditions and green emission under basic
      conditions, respectively. This study provides new materials with multimodalities
      for pH sensing and imaging.

PMID- 29210560
TI  - Reaction-Based Fluorescent Probes for the Imaging of Nitroxyl (HNO) in Biological
      Systems.
AB  - Nitroxyl (HNO) has been identified as an important signaling molecule in
      biological systems and plays critical roles in many physiological processes.
      Fluorescence imaging could provide a robust approach to explore the biological
      formation of HNO and its physiological functions. Herein, we summarize the
      organic reaction types for constructing HNO probes and specifically focus on
      review of the recent advances in the development of the reaction-based HNO probes
      and their imaging applications in living systems.

PMID- 29210561
TI  - Dual Function of UV/Ozone Plasma-Treated Polymer in Polymer/Metal Hybrid
      Electrodes and Semitransparent Polymer Solar Cells.
AB  - In this work, high-performance inverted indium tin oxide (ITO)-free
      semitransparent polymer solar cells are comprehensively investigated using a
      novel polymer/metal hybrid transparent electrode. The electrical and optical
      characteristics of hybrid electrodes are significantly enhanced by introducing
      UV/ozone plasma treatment on the polymer poly[(9,9-bis(3'-(N,N
      dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN), which
      is functioned as both a seed layer for ultrathin Ag metal electrode and an
      optical spacer for transparent devices. The optimized sheet resistance of PFN/Ag
      (12 nm) hybrid electrode is only half of the commercial ITO (9.4 vs 20.0 Omega sq
      1) and the high wavelength-dependent reflectance of hybrid electrode helps to
      increase the ITO-free device short-circuit current density. Furthermore, the
      interface property between PFN and ultrathin Ag is analyzed in detail and the
      optical field distribution is calculated for comparison. A high power conversion
      efficiency of 5.02%, which is increased by 35% compared to that of the ITO-based
      device, is achieved in the ITO-free semitransparent device in conjunction with an
      excellent average visible transmittance above 28% that is higher than the
      benchmark of 25% for power-generating window, indicating its great potential in
      building integrated photovoltaic systems in the future. Furthermore, the strategy
      is successfully developed for other polymer systems, suggesting the universal
      applicability for plastic electronics.

PMID- 29210562
TI  - Methacrylate-Stitched beta-Cyclodextrin Embedded with Nanogold/Nanotitania: A
      Skin Adhesive Device for Enhanced Transdermal Drug Delivery.
AB  - Transdermal (TD) drug delivery is a more attractive technique for drug delivery
      compared to oral and intravenous injection. However, the permeation of drug
      molecules across the skin is difficult due to the presence of highly ordered
      lipid barrier. This study details the development of a novel TD system, which has
      the potential to simultaneously enhance the skin permeability and adhesion
      behavior. Ibuprofen (IP) was selected as model drug. The ability of gold
      nanoparticle (AuNP) and hydrophobic titanium nanotube (TNT) to enhance the skin
      permeability was explored. Additionally, beta-cyclodextrin (betaCD), which can
      exceptionally encapsulate poorly water-soluble drugs, is grafted with
      methacrylates to improve the skin adhesion property. Finally, Au-TNT
      nanocomposite was deposited onto methacrylate-grafted betaCD matrix. The
      developed material was characterized through NMR spectroscopy, infrared
      spectroscopy, scanning electron microscopy, transmission electron microscopy, X
      ray diffraction, and Raman spectroscopy. The characteristics of the film,
      including water vapor permeability (WVP), thermomechanical properties, etc., were
      examined in terms of Au-TNT content. The TD delivery of IP with different
      concentrations of Au-TNT was evaluated via an in vitro skin permeation study
      through rat skin. It is revealed that the prepared TD film exhibited an improved
      drug-delivery performance due to the synergistic action of AuNP and hydrophobic
      TNT. The cumulative percent of IP delivered across the skin is extremely
      depending on nanofiller content, lipophilicity, and thickness of the membrane,
      and the device incorporated with 4.0% Au-TNT displayed the best performance. In
      addition, a study on storage stability was performed by storing the films for 2
      months at different temperatures. The study revealed that the device possessed
      excellent storage stability when stored at low temperature. The developed film
      offers excellent WVP, drug encapsulation efficiency, thermomechanical properties,
      and skin adhesion behavior. Moreover, the device was cosmetically attractive,
      noncytotoxic, and resistant to microbial growth and hence extremely reliable for
      skin application. The developed skin permeation strategy may open new avenues in
      TD drug delivery.

PMID- 29210563
TI  - Thermally Responsive Capillary Suspensions.
AB  - We demonstrate that stimulus-responsive capillary-structured materials can be
      formed from hydrophobized calcium carbonate particles suspended in a non-polar
      phase (silicone oil) and bridged by very small amounts of a hydrogel as the
      secondary aqueous phase. Inclusion of thermally responsive polymers into the
      aqueous phase yielded a capillary-structured suspension whose rheology is
      controlled by a change in temperature and can increase its complex modulus by
      several orders of magnitude because of the gelation of the capillary bridges
      between the solid particles. We demonstrate that the rheology of the capillary
      suspension and its response upon temperature changes can be controlled by the
      gelling properties as little as 0.1 w/w % of the secondary aqueous phase
      containing 2 wt % of the gelling carbohydrate. Doping the secondary (aqueous)
      phase with methyl cellulose, which gels at elevated temperatures, gave capillary
      structured materials whose viscosity and structural strength can increase by
      several orders of magnitude as the temperature is increased past the gelling
      temperature of the methyl cellulose solution. Increasing the methyl cellulose
      concentration from 0 to 2 w/w % in the secondary (aqueous) phase increases the
      complex modulus and the yield stress of the capillary suspension of 10 w/w %
      hydrophobized calcium carbonate in silicone oil by 2 orders of magnitude at a
      fixed temperature. By using an aqueous solution of a low melting point agarose as
      a secondary liquid phase, which melts as the temperature is raised, we produced
      capillary-structured materials whose viscosity and structural strength can
      decrease by several orders of magnitude as the temperature is increased past the
      melting temperature of the agarose solution. The development of thermally
      responsive capillary suspensions can find potential applications in structuring
      of smart home and personal care products as well as in temperature-triggered
      change in rheology and release of flavors in foods and actives in pharmaceutical
      formulations.

PMID- 29210564
TI  - In Situ Characterization of Photothermal Nanoenergetic Combustion on a Plasmonic
      Microchip.
AB  - Plasmonic gratings facilitate a robust in situ diagnostic platform for
      photothermal combustion of nanoenergetic composite thin films using an optical
      microscope and a high-speed camera. Aluminum nanoparticles (Al NPs) embedded in a
      fluoropolymer oxidizer are cast onto a plasmonic grating microchip and ignited
      using a low-power laser. The plasmonic grating enhances both spatial resolution
      and sufficient photothermal coupling to combust small Al NP clusters, initiating
      localized flames as small as 600 nm in size. Two-color pyrometry obtained from a
      high-speed color camera indicates an average flame temperature of 3900 K.
      Scattering measurements using polarized light microscopy enabled precise
      identification of individual Al NPs over a large field of view, leading to 3D
      reconstruction of combustion events.

PMID- 29210565
TI  - Microsphere Na0.65[Ni0.17Co0.11Mn0.72]O2 Cathode Material for High-Performance
      Sodium-Ion Batteries.
AB  - P2-type layered oxides have been considered promising candidates as cathodes for
      sodium-ion batteries (SIBs) owing to their high capacity and high rate
      capability. However, because of the difficulty involved in forming hierarchical
      microstructures, it remains challenging to develop high energy density P2-type
      layered oxides with good electrochemical performance and high electrode density.
      In this study, we demonstrate the feasibility of P2-type
      Na0.65[Ni0.17Co0.11Mn0.72]O2 as a very efficient cathode material for high energy
      density SIBs by synthesizing a micron-sized hierarchical structure via the
      coprecipitation route. The as-prepared P2-type microsphere cathode constructed
      from nanoscale primary particles provides a sufficient interface between the
      electrodes and the electrolyte solution, which enables to shorten the transport
      pathways for Na+ ions and electrons. Simultaneously, the hierarchical
      microstructure enhances the structural stability and high tap density (~1.18 g cm
      3). Benefiting from these merits, the proposed P2-type microsphere
      Na0.65[Ni0.17Co0.11Mn0.72]O2 displays a high discharge capacity of 187 mA h g-1
      at 12 mA g-1 and an exceptional cycle retention of 74.7% after 500 cycles, even
      at the high current density of 600 mA g-1. In addition, the high tap density of
      this P2-type microsphere enhances the density of composite cathodes, which
      translates to a high volumetric energy density of 340 W h L-1 based on the
      overall volume of the cathode active mass and the aluminum foil current
      collector.

PMID- 29210566
TI  - Multimodal MSI in Conjunction with Broad Coverage Spatially Resolved MS2
      Increases Confidence in Both Molecular Identification and Localization.
AB  - One critical aspect of mass spectrometry imaging (MSI) is the need to confidently
      identify detected analytes. While orthogonal tandem MS (e.g., LC-MS2) experiments
      from sample extracts can assist in annotating ions, the spatial information about
      these molecules is lost. Accordingly, this could cause mislead conclusions,
      especially in cases where isobaric species exhibit different distributions within
      a sample. In this Technical Note, we employed a multimodal imaging approach,
      using matrix assisted laser desorption/ionization (MALDI)-MSI and liquid
      extraction surface analysis (LESA)-MS2I, to confidently annotate and localize a
      broad range of metabolites involved in a tripartite symbiosis system of moss,
      cyanobacteria, and fungus. We found that the combination of these two imaging
      modalities generated very congruent ion images, providing the link between highly
      accurate structural information onfered by LESA and high spatial resolution
      attainable by MALDI. These results demonstrate how this combined methodology
      could be very useful in differentiating metabolite routes in complex systems.

PMID- 29210567
TI  - Correction to Empirical Correction for Differences in Chemical Exchange Rates in
      Hydrogen Exchange-Mass Spectrometry Measurements.

PMID- 29210568
TI  - Comparison of the Response of Bacterial IscU and SufU to Zn2+ and Select
      Transition-Metal Ions.
AB  - IscU, the central scaffold protein in the bacterial ISC iron-sulfur (Fe-S)
      cluster biosynthesis system, has long been recognized to bind a Zn2+ ion at its
      active site. While initially regarded as an artifact, Zn2+ binding has been shown
      to induce stabilization of the IscU structure that may mimic a state biologically
      relevant to IscU's role in Fe-S cluster biosynthesis. More recent studies have
      revealed that SufU, a homologous protein involved in Fe-S cluster biosynthesis in
      Gram-positive bacteria, also binds a Zn2+ ion with structural implications. Given
      the widespread occurrence of the "IscU-like" protein fold, particularly among Fe
      S cluster biosynthesis systems, an interesting question arises as to whether Zn2+
      ion binding and the resulting structural alterations are common properties in
      IscU-like proteins. Interactions between IscU and specific metal ions are
      investigated and compared side-by-side with those of SufU from a representative
      Gram-positive bacterium in the phylum Firmicutes. These studies were extended
      with additional transition metal ions chosen to investigate the influence of
      coordination geometry on selectivity for binding at the active sites of IscU and
      SufU. Monitoring and comparing the conformational behavior and stabilization
      afforded by different transition metal ions upon IscU and SufU revealed
      similarities between the two proteins and suggest that metal-dependent
      conformational transitions may be characteristic of U-type proteins involved in
      Fe-S cluster biosynthesis.

PMID- 29210569
TI  - Modulating DNA Repair Pathways to Improve Precision Genome Engineering.
AB  - Programmable nucleases like the popular CRISPR/Cas9 system allow for precision
      genome engineering by inducing a site-specific DNA double strand break (DSB)
      within a genome. The DSB is repaired by endogenous DNA repair pathways, either
      nonhomologous end joining (NHEJ) or homology directed repair (HDR). The
      predominant and error-prone NHEJ pathway often results in small nucleotide
      insertions or deletions that can be used to construct knockout alleles.
      Alternatively, HDR activity can result in precise modification incorporating
      exogenous DNA fragments into the cut site. However, genetic recombination in
      mammalian systems through the HDR pathway is an inefficient process and requires
      cumbersome laboratory methods to identify the desired accurate insertion events.
      This is further compromised by the activity of the competing DNA repair pathway,
      NHEJ, which repairs the majority of nuclease induced DNA DSBs and also is
      responsible for mutagenic insertion and deletion events at off-target locations
      throughout the genome. Various methodologies have been developed to increase the
      efficiency of designer nuclease-based HDR mediated gene editing. Here, we review
      these advances toward modulating the activities of the two critical DNA repair
      pathways, HDR and NHEJ, to enhance precision genome engineering.

PMID- 29210570
TI  - Single-Step LRET Aptasensor for Rapid Mycotoxin Detection.
AB  - Contamination of foods by mycotoxins is a common yet serious problem. Owing to
      the increase in consumption of fresh produce, consumers have become aware of food
      safety issues caused by mycotoxins. Therefore, rapid and sensitive mycotoxin
      detection is in great demand in fields such as food safety and public health.
      Here we report a single-step luminescence resonance energy transfer (LRET)
      aptasensor for mycotoxin detection. To accomplish the single-step sensor, our
      sensor was constructed by linking a quencher-labeled aptamer through a linker to
      the surface of upconversion nanoparticles (UCNPs). Our LRET aptasensor is
      composed of Mn2+-doped NaYF4:Yb3+,Er3+ UCNPs as the LRET donor, and black hole
      quencher 3 (BHQ3) as the acceptor. The maximum quenching efficiency is obtained
      by modulating the linker length, which controls the distance between the quencher
      and the UCNPs. Our distinctive design of LRET aptasensor allows detection of
      mycotoxins selectively in colored food samples within 10 min without multiple
      bioassay steps. We believe our single-step aptasensor has a significant potential
      for on-site detection of food contaminants, environmental pollutants, and
      biological metabolites.

PMID- 29210571
TI  - Molecular Engineering of alpha-Substituted Acrylate Ester Template for Efficient
      Fluorescence Probe of Hydrogen Polysulfides.
AB  - In this article, hydrogen polysulfide (H2Sn)-mediated Michael
      addition/cyclization cascade reactions toward acrylate ester analogues were
      exploited and utilized to construct novel and robust H2Sn-specific fluorescence
      probe for the first time. Through rational molecular engineering of the alpha
      substituted acrylate ester template, the optimal candidate probe FP-CF3
      containing trifluoromethyl-substituted acrylate ester group as recognition unit
      and 3-benzothiazol-7-hydroxycoumarin dye BHC as signal reporter can highly
      selectively detect H2Sn over other reactive sulfur species, especially biothiols
      including cysteine (Cys) and homocysteine (Hcy)/glutathione (GSH), with a rapid
      and significant turn-on fluorescence response (less than 60 s for response time
      and over 44-fold for signal-to-background ratio). The fast response and high
      selectivity of FP-CF3 for H2Sn could be attributed to a kinetically and spatially
      favored pentacyclic addition produced by the dual nucleophilic reaction of H2Sn
      with the CF3-substituted acrylate group. The big off-on fluorescence response is
      due to the pentacyclic intermediate results in the release of the highly
      fluorescent BHC. Moreover, it has been successfully applied in imaging of
      endogenous H2Sn fluctuation in living cells.

PMID- 29210572
TI  - Cobalt- and Rhodium-Corrole-Triphenylphosphine Complexes Revisited: The Question
      of a Noninnocent Corrole.
AB  - A reinvestigation of cobalt-corrole-triphenylphosphine complexes has yielded an
      unexpectedly subtle picture of their electronic structures. UV-vis absorption
      spectroscopy, skeletal bond length alternations observed in X-ray structures, and
      broken-symmetry DFT (B3LYP) calculations suggest partial CoII-corrole*2-
      character for these complexes. The same probes applied to the analogous rhodium
      corroles evince no evidence of a noninnocent corrole. X-ray absorption
      spectroscopic studies showed that the Co K rising edge of Co[TPC](PPh3) (TPC =
      triphenylcorrole) is red-shifted by ~1.8 eV relative to the bona fide Co(III)
      complexes Co[TPC](py)2 and Co[TPP](py)Cl (TPP = tetraphenylporphyrin, py =
      pyridine), consistent with a partial CoII-corrole*2- description for
      Co[TPC](PPh3). Electrochemical measurements have shown that both the Co and Rh
      complexes undergo two reversible oxidations and one to two irreversible
      reductions. In particular, the first reduction of the Rh corroles occurs at
      significantly more negative potentials than that of the Co corroles, reflecting
      significantly higher stability of the Rh(III) state relative to Co(III).
      Together, the results presented herein suggest that cobalt-corrole
      triphenylphosphine complexes are significantly noninnocent with moderate CoII
      corrole*2- character, underscoring-yet again-the ubiquity of ligand noninnocence
      among first-row transition metal corroles.

PMID- 29210573
TI  - Magnetic Levitation To Characterize the Kinetics of Free-Radical Polymerization.
AB  - This work describes the development of magnetic levitation (MagLev) to
      characterize the kinetics of free-radical polymerization of water-insoluble, low
      molecular-weight monomers that show a large change in density upon
      polymerization. Maglev measures density, and certain classes of monomers show a
      large change in density when monomers covalently join in polymer chains. MagLev
      characterized both the thermal polymerization of methacrylate-based monomers and
      the photopolymerization of methyl methacrylate and made it possible to determine
      the orders of reaction and the Arrhenius activation energy of polymerization.
      MagLev also made it possible to monitor polymerization in the presence of solids
      (aramid fibers, and carbon fibers, and glass fibers). MagLev offers a new
      analytical technique to materials and polymer scientists that complements other
      methods (even those based on density, such as dilatometry), and will be useful in
      investigating polymerizations, evaluating inhibition of polymerizations, and
      studying polymerization in the presence of included solid materials (e.g., for
      composite materials).

PMID- 29210574
TI  - Bis- and Tris(2-oxobenzimidazolyl)hydroborato Complexes of Sodium and Thallium:
      New Classes of Bidentate and Tridentate Oxygen Donor Ligands.
AB  - A series of bis- and tris(oxobenzimidazolyl)hydroborato compounds, namely,
      [BoRBenz]Na and [ToRBenz]-Na (R = Me, But, Ad), which feature uncommon sterically
      demanding LX [O2] and L2X [O3] donor ligands, have been obtained via the
      reactions of NaBH4 with 1-R-1,3-dihydro-2H-benzimidazol-2-ones. Evidence that the
      alkyl substituents are suitably located to have a significant impact on the
      coordination environment is provided by the observation that the methyl
      derivative [ToMeBenz]Na(kappa3-diglyme) exhibits kappa3-coordination of the
      diglyme, whereas the t-butyl and adamantyl derivatives, [ToButBenz]Na(kappa2
      diglyme) and [ToAdBenz]Na(kappa2-diglyme), exhibit kappa2-coordination. The
      [BoRBenz] and [ToRBenz] ligands also allow for isolation of discrete mononuclear
      thallium compounds, [BoRBenz]Tl and [ToRBenz]Tl, for which the steric demands of
      the ligands have been quantified in terms of both cone angle and buried volume
      concepts.

PMID- 29210575
TI  - Phase Separation Behavior of Supercharged Proteins and Polyelectrolytes.
AB  - Membraneless organelles, like membrane-bound organelles, are essential to cell
      homeostasis and provide discrete cellular subcompartments. Unlike classical
      organelles, membraneless organelles possess no physical barrier but rather arise
      by phase separation of the organelle components from the surrounding cytoplasm or
      nucleoplasm. Complex coacervation, the liquid-liquid phase separation of
      oppositely charged polyelectrolytes, is one of several phenomena that are
      hypothesized to drive the formation and regulation of some membraneless
      organelles. Studies of the molecular properties of globular proteins that drive
      complex coacervation are limited as many proteins do not form complexes with
      oppositely charged macromolecules at neutral pH and moderate ionic strengths.
      Protein supercharging overcomes this problem and drives complexation with
      oppositely charged macromolecules. In this work, several distinct cationic
      supercharged green fluorescent protein (GFP) variants were designed to examine
      the phase behavior with oppositely charged polyanionic macromolecules. Cationic
      GFP variants phase separated with oppositely charged macromolecules at various
      mixing ratios, salt concentrations, and pH values. Efficient protein
      incorporation in the macromolecule rich phase occurred over a range of protein
      and polymer mass fractions, but the protein encapsulation efficiency was highest
      at the midpoint of the phase separation regime. More positively charged proteins
      phase separated over broader pH and salt ranges than those of proteins with a
      lower charge density. Interestingly, each GFP variant phase separated at higher
      salt concentrations with anionic synthetic macromolecules compared to anionic
      biological macromolecules. Optical microscopy revealed that most variants,
      depending on solution conditions, formed liquid-liquid phase separations, except
      for GFP/DNA pairs that formed solid aggregates under all tested conditions.

PMID- 29210576
TI  - Valence Band Engineering of Layered Bismuth Oxyhalides toward Stable Visible
      Light Water Splitting: Madelung Site Potential Analysis.
AB  - A layered oxychloride Bi4NbO8Cl is a visible-light responsive catalyst for water
      splitting, with its remarkable stability ascribed to the highly dispersive O-2p
      orbitals in the valence band, the origin of which, however, remains unclear.
      Here, we systematically investigate four series of layered bismuth oxyhalides,
      BiOX (X = Cl, Br, I), Bi4NbO8X (X = Cl, Br), Bi2GdO4X (X = Cl, Br), and SrBiO2X
      (X = Cl, Br, I), and found that Madelung site potentials of anions capture
      essential features of the valence band structures of these materials. The oxide
      anion in fluorite-like blocks (e.g., [Bi2O2] slab in Bi4NbO8Cl) is responsible
      for the upward shift of the valence band, and the degree of electrostatic
      destabilization changes depending on building layers and their stacking sequence.
      This study suggests that the Madelung analysis enables a prediction and design of
      the valence band structures of bismuth and other layered oxyhalides and is
      applicable even to a compound where DFT calculation is difficult to perform.

PMID- 29210577
TI  - Design and Synthesis of Heteroleptic Iridium(III) Phosphors for Efficient Organic
      Light-Emitting Devices.
AB  - The phosphorescent emitters are essential to realize energy-efficient display and
      lighting panels. The solution processability is of particular interest for large
      scale and low-cost production. Here, we present a series of the heteroleptic
      iridium (Ir) complexes, Ir(ppy)2L1, Ir(ppy)2L2, and Ir(ppy)2L3, using the new
      ancillary ligands, including 1-(2-chlorophenyl)-5-hydroxy-3-methyl-1H-pyrazole-4
      carbaldehyde (L1), 5-hydroxy-3-methyl-1-(p-tolyl)-1H-pyrazole-4-carbaldehyde
      (L2), and 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (L3). Their
      photophysical and electrochemical properties were systematically characterized,
      followed by comparing with those predicted by density functional theory
      simulations using hybrid functionals. Among the three phosphors synthesized,
      Ir(ppy)2L1 exhibits the highest photoluminescence quantum yield (PhiPL = 89%),
      with an exciton lifetime of 0.34 MUs. By using 4,4'-bis(carbazole-9-yl)biphenyl
      as the host material, we demonstrate high current efficiencies of 64 and 40 cd A
      1 at 100 cd m-2 in its vacuum-evaporated and solution-processed organic light
      emitting devices, respectively, revealing the promise for large-area light
      sources.

PMID- 29210578
TI  - Lewis Acid-Base Adducts of Sc2C2@C3v(8)-C82/N-Heterocyclic Carbene: Toward
      Isomerically Pure Metallofullerene Derivatives.
AB  - The addition of a bulky N-heterocyclic carbene (NHC) to Sc2C2@C3v(8)-C82 affords
      two monoadducts (2a and 2b) quantitatively and regioselectively, representing the
      first examples of Lewis acid-base pairs of metal carbide cluster fullerenes. 2b
      is likely a kinetically favorable labile product that cannot be isolated from the
      solution. The crystallographic results of 2a unambiguously demonstrate that one
      polarized C-C single bond is formed between the normal carbene site C2N of the
      NHC and a specific [5,6,6]-carbon atom out of 17 types of nonequivalent cage
      carbon atoms of Sc2C2@C3v(8)-C82. Theoretical calculations demonstrate that the
      high regioselectivity, the unexpected addition pattern, and the quantitative
      formation of monoadducts are synergistic results from the cage geometry and
      electron distribution on the cage.

PMID- 29210579
TI  - Imaging Electrode Heterogeneity Using Chemically Confined Fluorescence
      Electrochemical Microscopy.
AB  - By varying the total and the relative concentrations of a strong acid (HClO4) and
      a pH-sensitive fluorescent dye (8-hydroxypyrene-1,3,6-trisulfonate), this work
      demonstrates that both the hydrogen evolution reaction or the oxygen reduction
      reaction can be selectively and optically studied at an electrochemical
      interface. The local pH shift driven by the redox reaction can be visualized
      through fluorescence imaging of the interface. The use of finite strong acid
      concentrations further serves to constrain the pH change to a thin layer adjacent
      to the surface. This chemical confinement of the fluorophore improves the
      system's resolution and enables micrometer scale heterogeneity on the electrode
      surface to be readily visualized.

PMID- 29210580
TI  - Photocurrent Enhancement by a Rapid Thermal Treatment of Nanodisk-Shaped SnS
      Photocathodes.
AB  - Photocathodes made from the earth-abundant, ecofriendly mineral tin monosulfide
      (SnS) can be promising candidates for p/n-type photoelectrochemical cells because
      they meet the strict requirements of energy band edges for each individual
      photoelectrode. Herein we fabricated SnS-based cell that exhibited a prolonged
      photocurrent for 3 h at -0.3 V vs the reversible hydrogen electrode (RHE) in a
      0.1 M HCl electrolyte. An enhancement of the cathodic photocurrent from 2 to 6 mA
      cm-2 is observed through a rapid thermal treatment. Mott-Schottky analysis of SnS
      samples revealed an anodic shift of 0.7 V in the flat band potential under light
      illumination. Incident photon-to-current conversion efficiency (IPCE) analysis
      indicates that an efficient charge transfer appropriate for solar hydrogen
      generation occurs at the -0.3 V vs RHE potential. This work shows that SnS is a
      promising material for photocathode in PEC cells and its performance can be
      enhanced via simple postannealing.

PMID- 29210581
TI  - Modeling of Human Fatty Acid Synthase and in Silico Docking of Acyl Carrier
      Protein Domain and Its Partner Catalytic Domains.
AB  - Human fatty acid synthase (hFAS) is a megasynthase whose main function is de novo
      biosynthesis of saturated fatty acids. Interest has been drawn to this enzyme
      beyond its physiological role due to the association between high levels of hFAS
      and clinical conditions such as obesity, diabetes, and cancer. Thus, it has
      become an undeniably attractive pharmacological target. Until now, no crystal
      structure of the complete hFAS is available, hindering attempts to fully
      understand this protein. Using homology modeling, we built a model of the entire
      megasynthase, encompassing all of its domains, including the acyl carrier protein
      (ACP) and thioesterase (TE) mobile domains absent in the crystal structure of
      mammalian fatty acid synthase (FAS). On a second stage, we used data-driven
      protein-protein docking between the substrate shuttling domain ACP and every
      catalytic domain in the protein. We also propose sets of amino acids at the
      interface of each domain that we believe are important to favor the interaction
      between ACP and each domain of hFAS. After inspection, we validated each complex
      between ACP and MAT/KS/KR/DH/ER domains through classical molecular dynamics
      simulations and RMSd analysis. Additionally, we mapped the interactions between
      the residues at the active site of each catalytic domain and its intermediaries.
      In every docking, we ensured that the distance between catalytic residues and the
      intermediaries was maintained. Until now, there was not a complete 3D model of
      this megasynthase. This study is the first to present a homology model for the
      whole hFAS, including its two mobile domains and possible poses of ACP throughout
      the cycle of fatty acid biosynthesis, thus mapping obligatory checkpoints in its
      trajectory. Hence, we believe that these structural insights will allow for
      future studies of the catalytic mechanism of the overall hFAS.

PMID- 29210582
TI  - Selective Suppression of Stimulated Raman Scattering with Another Competing
      Stimulated Raman Scattering.
AB  - A three-beam femtosecond stimulated Raman scattering (SRS) scheme is formulated
      and demonstrated to simultaneously induce two different SRS processes associated
      with Raman-active modes in the same molecule. Two SR gains involving a common
      pump pulse are coupled and compete: As one of the Stokes beam intensities
      increases, the other SRS is selectively suppressed. We provide theoretical
      description and experimental evidence that the selective suppression behavior is
      due to the limited number of pump photons used for both of the two SRS processes
      when an intense depletion beam induces one SRS process. The maximum suppression
      efficiency was ~60% with our experimental setup, where the SR gain of the ring
      breathing mode of benzene is the target SRS signal, which is allowed to compete
      with another SRS process, induced by an intense depletion beam, of the CH
      stretching mode. We anticipate a potential of this new switching-off concept in
      super-resolution label-free microscopy.

PMID- 29210583
TI  - Time-Resolved Infrared Spectroscopy on Plant Cryptochrome-Relevance of Proton
      Transfer and ATP Binding for Signaling.
AB  - Plant cryptochromes are light receptors in land plants and algae with very
      diverse functions such as circadian timing and lifecycle progression. The
      receptor consists of a photolyase homology region (PHR) binding the flavin
      chromophore and a C-terminal extension (CCT) responsible for signaling. The
      reputed signaling state, the flavin neutral radical, is formed by a femtosecond
      electron transfer and microsecond proton transfer to the excited, oxidized
      flavin. Subsequently, a 500 MUs loss of beta-sheet structure ~25 A away from
      flavin was resolved and suggested to be part of the signal conduction to the CCT.
      Here, we performed time-resolved, step-scan Fourier transform IR spectroscopy on
      the PHR of the plant cryptochrome pCRY (formerly CPH1) from Chlamydomonas
      reinhardtii. In a mutant lacking the proton donor aspartic acid 396 only the
      flavin anion radical is formed, but we observed the loss of beta-sheet structure
      with a time constant of 1.3 ms, similar to the 500 MUs of the wild type. This
      finding implies that the anion radical may be considered signaling-competent. In
      the steady state, a variation of external pH up to 8.3 did not have any effect on
      the difference spectra including the protonated state of Asp396. However, we
      detected the prominent loss of beta-sheet structure by illumination only in the
      presence of adenosine triphosphate (ATP). We conclude that the bound ATP
      stabilizes these light-induced changes in secondary structure to ensure a
      physiological lifetime compatible with signaling by plant cryptochrome.

PMID- 29210584
TI  - Stability of Substituted Phenyl Groups Electrochemically Grafted at Carbon
      Electrode Surface.
AB  - The electrochemical reduction of an aryl diazonium tetrafluoroborate salt,
      dissolved in acetonitrile, at a carbon electrode surface allowed the grafting of
      aryl groups with the formation of a carbon-carbon bond. Groups such as 4
      carboxyphenyl, 4-nitrophenyl, 4-diethylaniline (DEA), and 4-bromophenyl were
      grafted at a glassy carbon electrode surface. The stability of these grafted
      groups, present at the glassy carbon electrode surface, was studied at various
      electrode potentials in aqueous media. In appropriate experimental conditions,
      the as-grafted groups severely inhibit the cyclic voltammetry response of
      selected redox probes. Thus, the reappearance and/or increase of an
      electrochemical response, after polarization, was taken as an indication that a
      modification of the grafted layer occurred. Our results demonstrated that
      polarization at very positive (ca. 1.8 V) and negative (ca. -2 V) potentials is
      needed to observe an electrochemical response. Electrochemical impedance and X
      ray photoelectron spectroscopies were also used to investigate the stability of
      the grafted layers. The impedance data usually tracks fairly well the cyclic
      voltammetry results, although the former appears to be more sensitive to changes
      that are occurring upon polarization of the modified electrode. Interestingly,
      the XPS data indicate clearly that the grafted layer is not always completely
      removed at the extreme positive and negative potentials investigated. A mechanism
      was proposed to explain the transformation occurring during polarization of the
      modified electrode and involves desorption of the substituted aryl groups during
      the concomitant hydrogen, oxygen, or chlorine evolution and finally leaving close
      to a covalently bonded monolayer of the grafted species at the electrode surface.

PMID- 29210585
TI  - Sulfur-Containing Aristoloxazines and Other Constituents of the Roots of
      Aristolochia orbicularis.
AB  - Six new compounds, aristoloxazine A (1), aristoloxazine B (2), 7
      methoxytaliscanine (3), humul-7-en-1,4,11-triol (4), 8-hydroxy-beta-logipinene
      (5), and 1beta-hydroxy-4(14)-eudesmene (6), corresponding to two sulfur
      containing aristoloxazines (1 and 2), an aristolactam (3), and three
      sesquiterpenes (4-6) were isolated, along with 26 known compounds, from the roots
      of Aristolochia orbicularis. The structures of the new compounds were established
      based on their spectroscopic and spectrometric data and in the case of
      aristoloxazine A (1) by single-crystal X-ray crystallography. This is the first
      report of sulfur-containing aristoloxazines from a natural source. Furthermore,
      aristoloxazine A (1) was found to possess potent in vitro antimicrobial activity
      against all resistant Staphylococcus aureus and several fungal strains in which
      it was evaluated.

PMID- 29210586
TI  - Surface-Guided CsPbBr3 Perovskite Nanowires on Flat and Faceted Sapphire with
      Size-Dependent Photoluminescence and Fast Photoconductive Response.
AB  - All-inorganic lead halide perovskite nanowires have been the focus of increasing
      interest since they exhibit improved stability compared to their hybrid organic
      inorganic counterparts, while retaining their interesting optical and
      optoelectronic properties. Arrays of surface-guided nanowires with controlled
      orientations and morphology are promising as building blocks for various
      applications and for systematic research. We report the horizontal and aligned
      growth of CsPbBr3 nanowires with a uniform crystallographic orientation on flat
      and faceted sapphire surfaces to form arrays with 6-fold and 2-fold symmetries,
      respectively, along specific directions of the sapphire substrate. We observed
      waveguiding behavior and diameter-dependent photoluminescence emission well
      beyond the quantum confinement regime. The arrays were easily integrated into
      multiple devices, displaying p-type behavior and photoconductivity.
      Photodetectors based on those nanowires exhibit the fastest rise and decay times
      for any CsPbBr3-based photodetectors reported so far. One-dimensional arrays of
      halide perovskite nanowires are a promising platform for investigating the
      intriguing properties and potential applications of these unique materials.

PMID- 29210587
TI  - Organocatalytic Asymmetric Synthesis of Spiro-oxindole Piperidine Derivatives
      That Reduce Cancer Cell Proliferation by Inhibiting MDM2-p53 Interaction.
AB  - Asymmetric synthesis of pharmacologically interesting piperidine-fused spiro
      oxindole derivatives has been achieved via an organocatalytic Michael/aza
      Henry/hemiaminalization cascade reaction. Chiral compounds synthesized by this
      strategy potently inhibited the proliferation of several breast cancer cell
      lines. Mechanistic studies suggest that the most potent compound 9e can directly
      interfere with MDM2-p53 interactions and elevate protein levels of p53 and p21,
      thereby inducing cell cycle arrest and mitochondrial apoptosis.

PMID- 29210588
TI  - Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and SNAr Chemistry.
AB  - A hydrogen-transfer strategy for the catalytic functionalization of benzylic
      alcohols via electronic arene activation, accessing a diverse range of bespoke
      diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70%
      average yield), is reported. Taking advantage of the hydrogen-transfer approach,
      the oxidation level of the functionalized products can be selected by judicious
      choice of simple and inexpensive additives.

PMID- 29210589
TI  - Copper-Mediated Annulation of Phosphorus-Containing Arenes with Alkynes: An
      Approach to Phosphindolium Salts.
AB  - A novel method for the synthesis of pi-conjugated phosphindolium salts via copper
      mediated C-H functionalization of trisubstituted phosphines with alkynes in a
      single step is reported. The reactions are highly regioselective with
      unsymmetrical aryl-alkyl-substituted alkynes. This protocol provides an
      unprecedented atom- and step-efficient access to valuable phosphindolium salts.

PMID- 29210590
TI  - Weavable and Highly Efficient Organic Light-Emitting Fibers for Wearable
      Electronics: A Scalable, Low-Temperature Process.
AB  - Fiber-based wearable displays, one of the most desirable requisites of electronic
      textiles (e-textiles), have emerged as a technology for their capability to
      revolutionize textile and fashion industries in collaboration with the state-of
      the-art electronics. Nonetheless, challenges remain for the fibertronic
      approaches, because fiber-based light-emitting devices suffer from much lower
      performance than those fabricated on planar substrates. Here, we report weavable
      and highly efficient fiber-based organic light-emitting diodes (fiber OLEDs)
      based on a simple, cost-effective and low-temperature solution process. The
      values obtained for the fiber OLEDs, including efficiency and lifetime, are
      similar to that of conventional glass-based counterparts, which means that these
      state-of-the-art, highly efficient solution processed planar OLEDs can be applied
      to cylindrical shaped fibers without a reduction in performance. The fiber OLEDs
      withstand tensile strain up to 4.3% at a radius of 3.5 mm and are verified to be
      weavable into textiles and knitted clothes by hand-weaving demonstrations.
      Furthermore, to ensure the scalability of the proposed scheme fiber OLEDs with
      several diameters of 300, 220, 120, and 90 MUm, thinner than a human hair, are
      demonstrated successfully. We believe that this approach, suitable for cost
      effective reel-to-reel production, can realize low-cost commercially feasible
      fiber-based wearable displays in the future.

PMID- 29210591
TI  - Duplicate Type and Screen Testing: Waste in the Clinical Laboratory.
AB  - CONTEXT: - In the United States, approximately $65 billion dollars is spent per
      year on clinical laboratory testing, of which 20% to 30% of all testing is deemed
      inappropriate. There have been multiple studies in the field of transfusion
      medicine regarding evidence-based transfusion practices, but limited data exist
      regarding inappropriate pretransfusion testing and its financial and clinical
      implications. OBJECTIVE: - To assess duplicative testing practices in the
      transfusion medicine service. DESIGN: - A 24-month retrospective review was
      performed at a 1025-bed tertiary care center, identifying all duplicate type and
      screen (TS) tests performed within 72 hours of the previous TS. Duplicative
      testing was classified as appropriate or inappropriate by predetermined criteria.
      The level of underordering was analyzed through a query of the electronic event
      reporting system. A cost analysis was performed to determine the financial impact
      of inappropriate duplicative TS. RESULTS: - The mean rate of inappropriate,
      duplicative TS orders was 4.13% (standard deviation +/- 4.09%). Rates of
      inappropriate ordering ranged from 0.01% to 15.5% depending on the clinical
      service and did not correlate with volume of tests ordered. There were 8 reported
      cases of delayed blood delivery due to lack of a valid TS during the study
      period, demonstrating that underordering is also a harmful practice. The
      laboratory cost of inappropriate testing for the study period was $80,434, and
      phlebotomy costs were $45,469. CONCLUSIONS: - Our study demonstrates that
      inappropriate TS ordering is costly, both financially and clinically. By
      evaluating the percentage of inappropriate TS tests by clinical services, we have
      identified services that may benefit from additional education and technologic
      intervention.

PMID- 29210592
TI  - The Recent Pathology Residency Graduate Job Search Experience: A Synthesis of 5
      Years of College of American Pathologists Job Market Surveys.
AB  - CONTEXT: - Pathology residents and fellows tailor their training and job search
      strategies to an actively evolving specialty in the setting of scientific and
      technical advances and simultaneous changes in health care economics. OBJECTIVE: 
      To assess the experience and outcome of the job search process of pathologists
      searching for their first non-fellowship position. DESIGN: - The College of
      American Pathologists (CAP) Graduate Medical Education Committee has during the
      past 5 years sent an annual job search survey each June to CAP junior members and
      fellows in practice 3 years or less who have actively searched for a non
      fellowship position. RESULTS: - Job market indicators including job interviews,
      job offers, positions accepted, and job satisfaction have remained stable during
      the 5 years of the survey. Most survey respondents who had applied for at least 1
      position had accepted a position at the time of the survey, and most applicants
      who had accepted a position were satisfied or very satisfied. However, most
      attested that finding a non-fellowship position was difficult. Despite a
      perceived push toward subspecialization in surgical pathology, the reported
      number of fellowships completed was stable. Respondent demographics were not
      associated with job search success with 1 significant exception: international
      medical school graduate respondents reported greater perceived difficulty in
      finding a position, and indeed, fewer reported having accepted a position.
      CONCLUSIONS: - Pathology residents and fellows seeking their first position have
      faced a relatively stable job market during the last 5 years, with most accepting
      positions with which they were satisfied.

PMID- 29210593
TI  - Front-line treatment of patients with chronic lymphocytic leukemia: a systematic
      review and network meta-analysis.
AB  - AIM: A systematic literature review and network meta-analysis were conducted to
      determine the relative efficacy and safety of interventions for treatment-naive
      chronic lymphocytic leukemia patients, as comparative evidence is scarce.
      MATERIALS & METHODS: Relative treatment effects of progression-free survival,
      overall survival and safety outcomes were estimated via network meta-analysis
      based on data identified via systematic literature review. RESULTS: Ibrutinib was
      superior in all pairwise comparisons for progression-free survival (probability
      to be better [P] range: overall population: 69-100%; fludarabine-ineligible
      population: 69-100%) and overall survival (P range: overall: 89-100%; fludarabine
      ineligible: 91-100%) and had the highest probability of being best for all
      outcomes. CONCLUSION: Ibrutinib provides superior benefit in survival and safety
      compared with other front-line treatments of chronic lymphocytic leukemia.

PMID- 29210594
TI  - The Effect of CS Administration or an R-Optimized Alternative on R-PAS Variables:
      A Meta-Analysis of Findings From Six Studies.
AB  - Controlling the number of Rorschach responses (R) as a method to reduce
      variability in the length of records has stimulated controversy among researchers
      for many years. Recently, the Rorschach Performance Assessment System (R-PAS;
      Meyer, Viglione, Mihura, Erard, & Erdberg, 2011 ) introduced an R-Optimized
      method to reduce variability in R. Using 4 published and 2 previously unpublished
      studies (N = 713), we examine the extent to which 51 Comprehensive System-based
      scores on the R-PAS profile pages are affected as a result of receiving
      Comprehensive System (CS; Exner, 2003 ) administration versus a version of R
      Optimized administration. As hypothesized, R-the intended target of R-Optimized
      administration-showed reliable weighted average differences across each method of
      administration. As expected, its mean modestly increased and its standard
      deviation notably decreased. Also as hypothesized, the next largest effects were
      decreases in the variability (SD) of 2 variables directly related to R, R8910%
      and Complexity. No other reliable differences were observed. Therefore, because R
      Optimized administration does not notably modify the existing CS-based normative
      values for other profiled R-PAS variables, the data do not support concerns that
      R-Optimized administration notably modifies the Rorschach task or that existing
      CS research data would not generalize to R-PAS. However, because R-Optimized
      administration reduces variability in R, it allows a single set of norms to apply
      readily to more people.

PMID- 29210595
TI  - Evaluation of anionic surfactant removal by anaerobic degradation of commercial
      laundry wastewater and domestic sewage.
AB  - An expanded granular sludge bed reactor was evaluated for the anaerobic digestion
      of commercial laundry wastewater and domestic sewage focused on the removal of
      linear alkylbenzene sulfonate (LAS). The reactor was operated in three stages,
      all under mesophilic conditions and with a hydraulic retention time of 36 h. At
      stage I, the laundry wastewater was diluted with tap water (influent: 15.3 +/-
      4.9 mg LAS/L); at stage II, 50% of the feed volume was domestic sewage and 50%
      was a mixture of tap water and laundry wastewater (influent: 15.8 +/- 4.9 mg
      LAS/L); and at stage III, only domestic sewage was used as a diluent of the
      laundry wastewater (influent: 24.1 +/- 4.1 mg LAS/L). Due to the addition of
      domestic sewage the organic compounds content and LAS in the influent increased.
      Under such conditions, it was observed that LAS removal rate decreased from 77.2
      +/- 14.9% (stage I) to 55.3 +/- 18.4% (stage III). Statistical tests indicated
      that the decrease of the LAS removal rate was significant and indicated a
      correlation between the removal of LAS and specific organic loading rate. The
      analysis of 16S rRNA gene sequencing revealed genera similar to Geobacter,
      Desulfovibrio, Syntrophomonas, Syntrophus, Desulfobulbus, Desulfomonile, and
      Desulfomicrobium, which were related to the degradation of LAS.

PMID- 29210596
TI  - Mayo registry for telemetry efficacy in arrest study: An evaluation of the
      feasibility of the do not intubate code status.
AB  - INTRODUCTION: Guidelines recommend discussing code status with patients on
      hospital admission. No study has evaluated the feasibility of a full code with do
      not intubate (DNI) status. METHODS: A retrospective analysis of patients who
      experienced a cardiopulmonary arrest was performed between May 1, 2008 and June
      20, 2014. A descriptive analysis was created based on whether patients required
      mechanical ventilatory support during the hospitalization and comparisons were
      made between both patient subsets. RESULTS: A total of 239 patients were
      included. Almost all (n = 218, 91.2%) required intubation during the
      hospitalization. Over half (n = 117, 53.7%) were intubated on the same day as the
      cardiopulmonary arrest and 91 patients (41.7%) were intubated at the time of
      arrest. Comparisons between intubated and non-intubated patients showed little
      differences in clinical characteristics, except for a higher proportion of
      medical cardiac etiology for admission in patients who did not require intubation
      (n = 10, 47.6% versus n = 55, 25.2%; p = 0.18) and initial arrest rhythm of
      ventricular tachycardia/fibrillation (n = 8, 38.1% versus n = 50, 22.9%; p =
      0.37). No differences in 24-hour and posthospital survivals were present.
      CONCLUSION: Mechanical ventilatory support is commonly utilized in patients who
      experience a cardiopulmonary arrest. The DNI status may not be a feasible code
      status option for most patients.

PMID- 29210597
TI  - Spouse's subjective social status predicts older adults' prospective cognitive
      functioning.
AB  - OBJECTIVES: The current study aims to investigate the association between
      subjective social status (SSS) and prospective cognitive functioning of older
      adults and their spouses, and to explore the potential mediating roles of health
      habits and physical activities in this association. METHOD: Using the
      longitudinal data of 512 pairs of community-dwelling older couples aged 65-91
      years (M = 72.2 +/- 4.6), we tested the effects of SSS in cognitive functioning
      using an Actor-Partner Interdependence Model. SSS was measured by a self
      anchoring social ladder, and cognitive functioning was measured by the Mini
      Mental State Examination at baseline and 4-year follow-up. Socioeconomic status
      (i.e. education) was tested as a moderator, and physical activity (measured by
      the Physical Activity Scale for the Elderly) as well as health habits (i.e.
      tobacco and alcohol consumption) were included as potential mediators. RESULTS: A
      partner effect of SSS was found only in the low-education group, in which the
      wife's higher level of SSS in the community was associated with the husband's
      better cognitive functioning in the follow-up. A small proportion of this effect
      was found to be partially mediated by participation in housework, such that the
      wife's higher SSS was associated with the husband's increased housework activity,
      which was related to higher prospective cognitive functioning. CONCLUSION: By
      examining the dyadic effects of SSS with a longitudinal design, our findings
      extended the understanding on how subjective social status influenced older
      couples' cognitive health, and provided evidence-based insights for future
      studies on cognitive health in later life.

PMID- 29210599
TI  - Obesity in COPD: Revealed and Unrevealed Issues.
AB  - The interactions between obesity and chronic obstructive pulmonary disease (COPD)
      are being increasingly explored. In part, this is due to the globally increasing
      prevalence rates of obesity. The prevalence of obesity in COPD patients is
      variable, and it seems that obesity is more common in COPD patients compared with
      subjects who do not have COPD. However, further studies are encouraged in this
      area due to observed inconsistencies in the current data. In this review, we
      focus on the knowledge of the effects of obesity on dyspnea, pulmonary function,
      exercise capacity and exacerbation risk. Reduction of dyspnea is one of the main
      therapy targets in COPD care. There is still no consensus as to whether obesity
      has a negative or even a positive effect on dyspnea in COPD patients. It is
      hypothesized that obese COPD patients might benefit from favourable respiratory
      mechanics (less lung hyperinflation). However, despite less hyperinflation,
      obesity seems to have a negative influence on exercise capacity measured with
      weight-bearing tests. This negative influence is not seen with weight-supported
      exercise such as cycling. With respect to severe exacerbations, obesity seems to
      be associated with better survival. In summary, it is concluded that due to
      differences in study methodology and cohort selection, there are still too many
      knowledge gaps to develop guidelines for clinical practice. Further exploration
      is needed to get conclusive answers.

PMID- 29210600
TI  - Potential silver nanoparticles migration from commercially available polymeric
      baby products into food simulants.
AB  - In recent years, silver nanoparticles (AgNPs) have been extensively employed in
      food packaging systems as a potential antibacterial agent. Although proven to be
      highly effective, the increased number of AgNP-containing products raises
      concerns among consumers regarding the migration of AgNPs from the packaging
      material into foods, which may exert toxic effects. To address this, five baby
      products were chosen (baby bottle A, baby bottle B, pacifier A, pacifier B and
      breastmilk storage bag) to investigate AgNPs migration into three food simulants
      (deionised water, 4% acetic acid (w/v) and 50% ethanol (v/v)) using inductively
      coupled plasma mass spectrometry (ICP-MS). As a result, the highest level of
      migrated Ag was observed for 4% acetic acid in the case of baby bottle B,
      pacifier A, pacifier B and the breastmilk storage bag, with the detection amount
      ranging from 1.05-2.25 ng/mL. On the other hand, baby bottle A showed the maximum
      migration for 50% ethanol due to the polymer nature. Finally, a centrifugal
      ultrafiltration experiment was conducted to determine the fraction of dissolved
      Ag in acidic simulant and it was found that migrated Ag was predominantly in Ag+
      form, with a small fraction of non-ionic AgNPs. Thus, it has been found that the
      amount of migrated Ag in baby products was low; however, the migration was
      dependent on the type of food simulant and polymer nature.

PMID- 29210601
TI  - Ranking Quantitative Resistance to Septoria tritici Blotch in Elite Wheat
      Cultivars Using Automated Image Analysis.
AB  - Quantitative resistance is likely to be more durable than major gene resistance
      for controlling Septoria tritici blotch (STB) on wheat. Earlier studies
      hypothesized that resistance affecting the degree of host damage, as measured by
      the percentage of leaf area covered by STB lesions, is distinct from resistance
      that affects pathogen reproduction, as measured by the density of pycnidia
      produced within lesions. We tested this hypothesis using a collection of 335
      elite European winter wheat cultivars that was naturally infected by a diverse
      population of Zymoseptoria tritici in a replicated field experiment. We used
      automated image analysis of 21,420 scanned wheat leaves to obtain quantitative
      measures of conditional STB intensity that were precise, objective, and
      reproducible. These measures allowed us to explicitly separate resistance
      affecting host damage from resistance affecting pathogen reproduction, enabling
      us to confirm that these resistance traits are largely independent. The cultivar
      rankings based on host damage were different from the rankings based on pathogen
      reproduction, indicating that the two forms of resistance should be considered
      separately in breeding programs aiming to increase STB resistance. We hypothesize
      that these different forms of resistance are under separate genetic control,
      enabling them to be recombined to form new cultivars that are highly resistant to
      STB. We found a significant correlation between rankings based on automated image
      analysis and rankings based on traditional visual scoring, suggesting that image
      analysis can complement conventional measurements of STB resistance, based
      largely on host damage, while enabling a much more precise measure of pathogen
      reproduction. We showed that measures of pathogen reproduction early in the
      growing season were the best predictors of host damage late in the growing
      season, illustrating the importance of breeding for resistance that reduces
      pathogen reproduction in order to minimize yield losses caused by STB. These data
      can already be used by breeding programs to choose wheat cultivars that are
      broadly resistant to naturally diverse Z. tritici populations according to the
      different classes of resistance.

PMID- 29210602
TI  - Assessment of the comparability of CLSI, EUCAST and Stokes antimicrobial
      susceptibility profiles for Escherichia coli uropathogenic isolates.
AB  - BACKGROUND: As many clinical laboratories convert between Stokes, Clinical and
      Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial
      Susceptibility Testing (EUCAST) methods, the problem of comparing differently
      derived sets of antimicrobial susceptibility testing (AST) data with each other
      arises, owing to a scarcity of knowledge of inter-method comparability. The
      purpose of the current study was to determine the comparability of CLSI, EUCAST
      and Stokes AST methods for determining susceptibility of uropathogenic
      Escherichia coli to ampicillin, amoxicillin-clavulanate, trimethoprim,
      cephradine/cephalexin, ciprofloxacin and nitrofurantoin. METHODS: A total of 100
      E. coli isolates were obtained from boric acid urine samples from patients
      attending GP surgeries. For EUCAST and CLSI, the Kirby-Bauer disc diffusion
      method was used and results interpreted using the respective breakpoint
      guidelines. For the Stokes method, direct susceptibility testing was performed on
      the urine samples. RESULTS: The lowest levels of agreement were for amoxicillin
      clavulanate (60%) and ciprofloxacin (89%) between the three AST methods, when
      using 2017 interpretive guidelines for CLSI and EUCAST. A comparison of EUCAST
      and CLSI without Stokes showed 82% agreement for amoxicillin-clavulanate and 94%
      agreement for ciprofloxacin. Discrepancies were compounded by varying breakpoint
      susceptibility guidelines issued during the period 2011-2017, and through the
      inclusion of a definition of intermediate susceptibility in some cases.
      CONCLUSIONS: Our data indicate that the discrepancies generated through using
      different AST methods and different interpretive guidelines may result in
      confusion and inaccuracy when prescribing treatment for urinary tract infection.

PMID- 29210603
TI  - An unexpected switch in peptide binding mode: from simulation to substrate
      specificity.
AB  - A ten microsecond molecular dynamics simulation of a kallikrein-related peptidase
      7 peptide complex revealed an unexpected change in binding mode. After more than
      two microseconds unrestrained sampling we observe a spontaneous transition of the
      binding pose including a 180 degrees  rotation around the P1 residue.
      Subsequently, the substrate peptide occupies the prime side region rather than
      the cognate non-prime side in a stable conformation. We characterize the
      unexpected binding mode in terms of contacts, solvent-accessible surface area,
      molecular interactions and energetic properties. We compare the new pose to
      inhibitor-bound structures of kallikreins with occupied prime side and find that
      a similar orientation is adopted. Finally, we apply in silico mutagenesis based
      on the alternative peptide binding position to explore the prime side specificity
      of kallikrein-related peptidase 7 and compare it to available experimental data.
      Our study provides the first microsecond time scale simulation data on a
      kallikrein protease and shows previously unexplored prime side interactions.
      Therefore, we expect our study to advance the rational design of inhibitors
      targeting kallikrein-related peptidase 7, an emerging drug target involved in
      several skin diseases as well as cancer.

PMID- 29210605
TI  - Cognitive and behaviour profiles of children with mucopolysaccharidosis Type II.
AB  - Mucopolysaccharidosis Type II (MPS II) or Hunter Syndrome is a rare X-linked
      condition, due to a defect in a lysosomal enzyme involved in the breakdown of
      glycosaminoglycans. It is a progressive condition with worsening over time;
      however, symptom severity and progression rates vary. Normal intellectual
      function has been reported in males with mild MPS II but few studies are
      available that provide comprehensive cognitive profiles. Enzyme replacement
      therapy (ERT) can stabilize physical symptoms and has become standard treatment.
      Whether ERT can influence cognition is currently unknown. Considering this, we
      conducted cognitive, fine motor, and behavioural assessments with three males
      (7;6-12;1 years) with mild MPS II before and after ERT. Generally, cognition,
      fine motor skills, and behaviour were in the normal range; however, specific
      deficits in attention and executive function were identified. Following ERT, some
      memory improvements were seen. Executive deficits remained, and processing speed
      declined over time.

PMID- 29210606
TI  - Development and validation of a confirmatory method for the determination of
      stilbene estrogens in ostrich serum.
AB  - A simple and accurate ultra-high-performance liquid chromatography tandem mass
      spectrometry (UHPLC-MS/MS) method was developed and validated for the first time
      as a confirmatory method for the simultaneous determination of stilbenes -
      hexestrol and diethylstibestrol in serum. Extraction was based on a simple acid
      denaturation of protein followed by liquid-liquid extraction using methyl tert
      butyl ether. Extracts were directly injected into the UHPLC-MS/MS without further
      purification. Excellent recoveries in the range 82-99% and 91-128% were obtained
      for hexestrol and diethylstibestrol, respectively. Both within-day repeatability
      and between-day reproducibility were generally satisfactory with RSD <20%. The
      linearity of the internal standard based matrix-matched calibration curve
      measured as the coefficient of regression (r2) was generally >0.99 for both
      hexestrol and diethylstibestrol. Both matrix effect and uncertainties associated
      with sample preparation and instrumental analysis were significantly reduced with
      the use of a deuterated compound (hexestrol-d4) as internal standard. The LOD and
      LOQ were 0.09 and 0.08 ng/ml, and 0.28 and 0.25 ng/ml, respectively, for
      hexestrol and diethylstibestrol. The method was found to be suitable for the
      simultaneous determination of hexestrol and diethylstibestrol in serum.

PMID- 29210607
TI  - Detection of anorexia nervosa in primary care.
AB  - In the years preceding diagnosis, individuals with anorexia nervosa (AN) attend
      more primary care appointments than their peers. Primary care physicians (PCPs)
      may be uniquely situated to detect AN in early manifestations. In this study, a
      sample of physicians was recruited online. Videotaped vignettes of a primary care
      appointment were shown to these participants, who were asked to diagnose the
      patient and could make a referral. 61.2% of participants identified an eating
      disorder (ED) diagnosis. However, of those, only 40% intended to refer for
      therapy. These findings suggest that the rate of referral to mental health is
      problematically low among PCPs.

PMID- 29210608
TI  - Occurrence and risk assessment of population exposed to deoxynivalenol in foods
      derived from wheat flour in Brazil.
AB  - Deoxynivalenol (DON) is the most important of the trichothecenes in terms of
      amounts and occurrence in wheat. This compound was shown to be associated with a
      glomerulonephropathy involving an increase of immunoglobulin A in humans. This
      study assessed the occurrence of DON in wheat flour and the exposure of Brazilian
      teenagers, adults and elderly to this mycotoxin due to intake of wheat flour
      based products. DON extraction in wheat flour was carried out by solid phase
      extraction and the quantification was performed by ultra-high proficiency liquid
      chromatography with diode-array detection. A total of 77.9% of all samples were
      positive for DON, with concentrations ranging from 73.50 to 2794.63 ug kg-1. The
      intake was calculated for the average and 90th percentile of the contamination
      levels of DON in foods based-wheat for teenagers, adults and elderly in Brazil,
      and compared with the provisional maximum tolerable daily intakes (PMTDI).
      Females of all age groups were exposed to DON at higher levels when compared to
      males in regard of consumption of breads and pastas. Teenagers were the main
      consumers of foods derived from wheat flour, with maximum probable daily intakes
      of 1.28 and 1.20 ug kg-1 b.w. day-1 for females and males, respectively. This
      population is at an increased risk of exposure to DON due to consumption of wheat
      flour-based foods in Brazil.

PMID- 29210609
TI  - Dietary intakes of six intense sweeteners by Irish adults.
AB  - This research investigated the intakes of six intense sweeteners: acesulfame-K
      (E950), aspartame (E951), cyclamate (E952), saccharin (E954), sucralose (E955),
      and steviol glycosides (E960) in the diets of Irish adults, using data from the
      National Adult Nutrition Survey. A food label survey that included products
      currently available on the Irish market supplemented the analysis. Sweetener
      intakes were investigated using three different exposure scenarios; beginning
      with a crude assessment which assumed that all foods permitted to contain the
      additives of interest always did contain them, and at their maximum permitted
      level (Tier 1). Refined assessments estimated intakes of the six sweeteners using
      food consumption data up to brand level with additive occurrence data from a
      survey of products currently available on the Irish market (Tier 2) and sweetener
      concentration data (Tier 3). Results of all exposure assessment scenarios
      demonstrate that intakes of each of the sweeteners of interest by the total
      population were below the relevant ADI level (mg kg-1 bodyweight-1), even by high
      consumers (P99). The three sweeteners consumed in highest amounts were acesulfame
      k, aspartame, and sucralose. The main sources of these sweeteners in the diet
      were 'cider and perry', 'energy reduced and no added sugar (ER and NAS)
      carbonated flavoured drinks', 'table-top sweeteners', 'dairy products', 'solid
      food supplements', and 'sauces'. Intakes of the six intense sweeteners are
      currently not a concern among Irish adults. However, exposure to these chemicals
      should be monitored on a regular basis due to evolving market and consumption
      patterns.

PMID- 29210610
TI  - Effects of feeding bentonite clay upon ochratoxin A-induced immunosuppression in
      broiler chicks.
AB  - A presence of mycotoxins in feed is one of the most alarming issues in the
      poultry feed industry. Ochratoxins, produced by several Aspergillus and
      Penicillium species, are important mycotoxin regarding the health status of
      poultry birds. Ochratoxins are further classified into to several subtypes (A, B,
      C, etc) depending on their chemical structures, but ochratoxin A (OTA) is
      considered the most important and toxic. Bentonite clay, belonging to
      phyllosilicates and formed from weathering of volcanic ashes, has adsorbent
      ability for several mycotoxins. The present study was designed to study the
      effects of bentonite clay upon OTA-induced immunosuppression in broiler chicks.
      For this, 480 day-old broiler chicks were procured from a local hatchery and then
      different combinations of OTA (0.15, 0.3, or 1.0 mg/kg) and bentonite clay (5,
      10, and 20 g/kg) were incorporated into their feed. At 13, 30, and 42 days of
      age, parameters such as antibody responses to sheep red blood cells, in situ
      lymphoproliferative responses to mitogen (PHA-P), and in situ phagocytic activity
      (i.e., via carbon clearance) were determined respectively. The results indicated
      there was a significant reduction of total antibody and immunoglobulin titres,
      lymphoproliferative responses, and phagocytic potential in OTA-treated birds,
      suggesting clear immunosuppression by OTA in birds in a dose-dependent manner.
      These results were also significantly lower in all combination groups (OTA with
      bentonite clay), suggesting few to no effects of feeding bentonite clay upon OTA-
      induced alterations in different immune parameters.

PMID- 29210611
TI  - Tracking residual organochlorine pesticides (OCPs) in green, herbal, and black
      tea leaves and infusions of commercially available tea products marketed in
      Poland.
AB  - The content of residual organochlorine pesticides (OCPs) was examined in green,
      herbal, and black tea leaves as well as in their infusions prepared from tea
      products marketed in the main supermarkets in Poland. It was found that the
      detected mean levels of organochlorine residues in tea leaves ranged from <LOD to
      16.36 ng g-1 dry weight. Among hexachlorocyclohexane isomers, gamma-HCH in green
      tea occurred in the highest concentrations. Among dichlorodiphenyltrichloroethane
      (DDT) metabolites the highest level of p,p'DDT (1.96 ng g-1 dw) was in green tea
      samples. The transfer of OCPs from tea leaves to brew was investigated. The
      present study revealed that during the infusion process, a significant percentage
      of the residues, particularly pesticides with high water solubility, were
      transferred to the infusions. The obtained results show that the percentage
      transfer of each pesticides from tea to the tea infusions ranged from 6.74%
      (heptachlor) to 86.6% (endrin). The detected residues were below current MRLs for
      these pesticides.

PMID- 29210612
TI  - Association of Fine Motor Loss and Allodynia in Fibromyalgia: An fNIRS Study.
AB  - Recent studies showed that fine motor control dysfunction was observed in
      fibromyalgia (FM) syndrome as well as allodynia. However, brain signatures of
      this association still remain unclear. In this study, finger tapping task (FTT)
      and median nerve stimulation (MNS) were applied to both hands of 15 FM patients
      and healthy controls (HC) to understand this relationship. Hemodynamic activity
      was measured simultaneously using functional near-infrared spectroscopy (fNIRS).
      Experiments were analyzed separately by using 2x2 repeated measures ANOVA.
      Results for the FTT experiment revealed that HC showed higher activity than FM
      patients in bilateral superior parietal gyrus (SPG), left supramarginal gyrus
      (SMG) and right somatosensory cortex (SI). Furthermore, right-hand FTT resulted
      in higher activity than left-hand FTT in left SPG, left SI and right motor cortex
      (MI). In the MNS experiment, FM patients showed higher activity than HC in
      bilateral SPG, right SMG, right SI and right middle frontal gyrus (MFG). Negative
      correlation was observed in left SPG between FTT and MNS activities. Besides, MNS
      activity in left SPG was negatively correlated with left-hand pain threshold.This
      study revealed that left SPG might be an important indicator to associate fine
      motor loss and allodynia in FM.

PMID- 29210613
TI  - Reproductive tract infection and related factors among female migrants working in
      industrial zones in Vietnam 2013-2014.
AB  - We conducted this study to analyze factors related to reproductive tract
      infections (RTIs) among female migrant workers (FMWs) in four industrial zones
      across four regions in Vietnam. A analytical cross-sectional study was
      implemented with FMWs aged between 18 and 49 year old in four industrial zones in
      Hanoi, Da Nang, Ho Chi Minh (HCM) city and Binh Duong, Vietnam. Stratified
      sampling was used to select about 6400 married and unmarried FMWs. Cases were
      identified through self-reporting of female migrants concerning RTIs symtoms
      experienced in the 1 year prior to the study. Based on multivariate logistic
      regression results, we suggested that about 32% of FMWs reported having RTIs
      problems (27.6% in Hanoi, 30.3% in Danang, 36% in HCMC and 32.9% in Binhduong).
      We also identified different factors related to RTIs among different study sites.
      Marital status, level of education, social-economic status and numbers of
      migration were important related factors of RTIs.

PMID- 29210614
TI  - Recycled paperboard with a barrier layer for food contact: set-off during
      stacking or reeling. Analytical method and preliminary results.
AB  - The use of recycled paperboard for packaging dry foods is in the interest of
      sustainability of resources, but in most applications, the food must be protected
      against contamination, such as by a functional barrier on the internal surface of
      the paperboard box. After application, the paperboard is usually stacked or
      reeled before making boxes. During this period, the food-contact surface of the
      barrier layer is in contact with the outer side of the paperboard, which may
      result in set-off and subsequent contamination of food. A method is described for
      the determination of this path of migration, based on the taped format also used
      for the measurement of the barrier efficiency. Recycled paperboard containing the
      three surrogate substances n-heptadecane, 4-methyl benzophenone and dipropyl
      phthalate was taped to the food-contact side of the barrier layer. Pressure onto
      the test packs did not seem to be a relevant parameter. After periods of
      interest, a piece of the paperboard with the barrier layer was extracted and
      analysed for the surrogate substances. Another piece may be brought into contact
      with silicone paper to simulate the transfer to food. After 2 weeks at 60 degrees
      C (simulating about 1 year at 25 degrees C), set-off and the transfer to the
      silicone paper exceeded 1% for all barrier materials tested, but after 6 weeks at
      40 degrees C (around half a year at 25 degrees C), set-off remained below 1% for
      all barrier layers except a multilayer with polyethylene on the food-contact
      surface. The preliminary conclusion is that set-off should be taken seriously,
      but may be kept low enough to provide sufficient protection of the packed food.

PMID- 29210615
TI  - Dietary exposure to non-dioxin-like PCBs of the Hong Kong adult population from a
      total diet study.
AB  - Dietary exposure of Hong Kong adults to the sum of the six indicator PCBs (Sigma6
      PCBs; PCB 28, 52, 101, 138, 153, and 180) was estimated in this study using the
      Total Diet Study (TDS) approach. Seventy one commonly-consumed food items of
      animal origin were sampled in four seasons and prepared as consumed in 2010-2011.
      The results showed that the main dietary source of Sigma6 PCBs to the adult
      population was 'fish, seafood and their products' which accounted for 84.3% of
      the total exposure. About 50% of the total exposure was contributed by four fish
      species: salmon (cooked salmon and salmon sashimi, 19.9%), mandarin fish (14.7%),
      pomfret fish (8.5%) and yellow croaker (7.5%). Salmon was found to contain the
      highest mean level of Sigma6 PCBs of 5.7 ng g-1 fresh weight at upper bound
      estimation, ranging from 4.4 to 6.3 ng g-1. The lower bound and upper bound
      exposure estimates of ?6 PCBs to the average consumer of the population were
      found to be 0.68 and 1.38 ng kg-1 body weight day-1 respectively while for high
      consumers, the lower bound and upper bound exposure estimates were 3.08 and 3.84
      ng kg-1 body weight day-1 respectively. In addition, the dietary exposures to
      individual indicator PCB congeners were also estimated.

PMID- 29210616
TI  - Mothers' willingness to pay for daughters' HPV vaccine in northern Vietnam.
AB  - HPV vaccine is effective in preventing human papillomavirus, the main cause of
      cervical cancer. In Vietnam, at first, it was subsidized at $5 a dose and reached
      the coverage of 96% in two pilot provinces, indicating potentially high
      acceptance. Currently, it is provided at $120-195 for three doses. This is a
      cross-sectional study, conducted in two northern rural districts of Vietnam.
      Researchers present findings to show 53.1% of mothers stated their willingness to
      pay (WTP) for HPV vaccine for their daughters. Perceptions on cost and condom use
      were associated with WTP. Mothers' affordability ranged from under $23 to $46.
      Measures should be implemented soon to make HPV vaccine more affordable.

PMID- 29210617
TI  - A Meta-analysis of the Correlation between Maltreatment, Witnessing Domestic
      Violence, and Bullying among Youths in South Korea.
AB  - The aim of this meta-analysis is to examine synthesized correlation outcomes
      between maltreatment, witnessing domestic violence, and bullying among youths in
      South Korea. The study examined 42 studies from between 2000 and 2015; the
      results showed that there is a medium effect size for this association among
      youths. Specifically, the effect size of the association was found to be larger
      for physical and verbal/emotional abuse and neglect than exposure to domestic
      violence for youths. The authors suggest that effective prevention and
      intervention for youths who are at risk of suffering maltreatment and witnessing
      domestic violence may help them avoid developing bullying behaviors.

PMID- 29210619
TI  - Gray divorce: Explaining midlife marital splits.
AB  - Recent research suggests that one out of every four divorces in the United States
      is now "gray," meaning that at least one half of the couple has reached the age
      of 50 when the marriage breaks down. To understand why this age group-the Baby
      Boomer generation-is splitting up, this study conducted 40 in-depth,
      semistructured interviews with men and 40 with women who have experienced a gray
      divorce in their lifetimes. Respondents' beliefs in an expressive individualistic
      model of marriage, where partnerships are only valuable if they help individuals
      achieve personal growth, were compared against their potential adherence to what
      I call a commitment-based model of marriage, where binding, romantic love holds
      couples together unless there is severe relationship strain. The results
      demonstrated that the commitment-based model most strongly governs marriage and
      the decision to divorce among Baby Boomers for both sexes, although some specific
      reasons for divorce differ for men and women.

PMID- 29210618
TI  - Simultaneous determination of kasugamycin and validamycin-A residues in cereals
      by consecutive solid-phase extraction combined with liquid chromatography-tandem
      mass spectrometry.
AB  - Two polar aminoglycosides, kasugamycin and validamycin-A, were determined in
      cereals (brown rice, wheat and corn) by high-performance liquid chromatography
      tandem mass spectrometry. The analytes were extracted from samples using methanol
      and water (70:30, v/v) at pH 5.5, purified using both a hydrophilic-hydrophobic
      balanced cartridge and a strong cation-exchange cartridge, and then analysed
      using multiple reaction monitoring in positive electrospray ionisation mode with
      a special ReproSil 100 C18 high-performance liquid chromatography column. This
      newly proposed method yielded good sensitivity and excellent chromatographic
      performance. The limits of quantification for kasugamycin and validamycin-A were
      4.1 ug/kg and 1.0 ug/kg, respectively. The recoveries for both compounds at three
      fortification levels (4, 100 and 500 ug/kg for kasugamycin; 1, 10 and 100 ug/kg
      for validamycin-A) ranged from 75% to 110%, and the relative standard deviations
      were below 15%.

PMID- 29210621
TI  - Pathways to pleasure: Older adult women's reflections on being sexual beings.
AB  - Older adult women make up a growing part of the population, and yet literature on
      the sexual activity over their life spans is lacking. This qualitative interview
      study explored the experience of 16 women aged 57-91 to better understand sexual
      pleasure over a lifetime. The participants described having to challenge cultural
      rules to create a supportive environment for sexual expression. Having access to
      Novel contexts in which to learn, cultivating Intimacy with partners and with
      oneself, being Creative with sexual activities, and Extending one's sense of
      sexual possibility into advanced age (NICE) supported sexual pleasure as women
      aged.

PMID- 29210620
TI  - Association between Social Capital and Self-Efficacy among Latinas in Nebraska.
AB  - Ensuring the health and well-being of Latinas is critical given the size of the
      population and its rapid growth across the United States. Social capital may be a
      tool for alleviating some of the individual, neighborhood, and societal
      challenges that Latina immigrants face. This study uses bivariate tests and
      multivariate regression to assess the association between social capital and self
      efficacy among Latina immigrants in the Midwest (N = 94). Self-efficacy was
      positively correlated with bonding and bridging social capital. Findings from a
      multiple regression model indicate that bonding and bridging social capital are
      significantly associated with self-efficacy after adjusting for the effect of
      related covariates. Public health interventions may benefit from building and
      fostering bonding and bridging social capital among immigrants as way to improve
      self-efficacy, promote health, and enhance public health practice.

PMID- 29210622
TI  - Examining Successful Aging in Women.

PMID- 29210626
TI  - Short-term cost and efficiency analysis of raltegravir versus
      atazanavir/ritonavir or darunavir/ritonavir for treatment-naive adults with HIV-1
      infection in Spain.
AB  - INTRODUCTION: The AIDS Clinical Trial Group (ACTG) 5257 clinical trial showed
      that raltegravir (RAL) was superior to atazanavir/ritonavir (ATV/r) and
      darunavir/ritonavir (DRV/r), when used in combination with
      emtricitabine/tenofovir DF (FTC/TDF), in a 96-week composite endpoint combining
      virologic efficacy and tolerability for treatment-naive adults with HIV-1
      infection. This study aimed to estimate the efficiency associated with these
      three regimens in Spain. METHODS: An economic model was developed to estimate
      costs for antiretroviral drugs, adverse event management, and HIV care for
      individuals initiating first-line therapy. Antiretroviral drug costs were based
      on hospital costs with mandatory discounts applied. Adverse event management
      costs and HIV care costs were obtained from published sources and inflated to
      2015 euros. Head-to-head efficacy and safety data (discontinuation rates, mean
      CD4 cell-count changes, adverse event incidence) up to 96 weeks for each regimen
      were obtained from the clinical trial. The efficiency of each regimen, as
      measured by the cost per successfully treated patient (i.e. on first-line therapy
      for 96 weeks), was estimated and examined in sensitivity analyses. All cost
      outcomes were discounted at 3.0% annually. RESULTS: Total costs per successfully
      treated patient were ?22,377 for RAL, ?26,629 for ATV/r, and ?23,928 for DRV/r.
      These results were found to be robust in sensitivity analyses. DISCUSSION: RAL
      has the lowest cost per successfully treated patient when compared with DRV/r and
      ATV/r, each used in combination with FTC/TDF, for treatment-naive adults with HIV
      1 infection in Spain. This economic evidence complements the clinical benefits of
      RAL reported in the ACTG 5257 clinical trial.

PMID- 29210625
TI  - Evaluation of oral serum-derived bovine immunoglobulins in HIV-infected patients
      with chronic idiopathic diarrhea.
AB  - Objectives To evaluate serum-derived bovine immunoglobulin/protein isolate (SBI)
      for safety and impact on gastrointestinal (GI) symptoms in HIV patients with
      chronic idiopathic diarrhea. Methods A multi-center trial comprised of a double
      blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI
      at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at
      either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were
      virologically suppressed with a history of chronic idiopathic diarrhea, defined
      as > 3 loose stools per day for >= 3 months without an identifiable cause. Safety
      was evaluated by monitoring adverse events (AEs) and clinical laboratory testing.
      Health status and changes in GI symptoms were assessed using validated
      questionnaires. Results SBI was well tolerated by the 103 participants with only
      2 withdrawals due to AEs potentially associated with SBI. Mean number of daily
      unformed stools decreased from about 4 at baseline to less than 2 by week 4 for
      all study groups. Improvements in several other GI symptoms were also reported.
      Comparison of the PBO group to SBI groups showed no significant differences,
      although both SBI cohorts reported significantly improved health status scores.
      GI symptom improvements were maintained throughout the 20-week PBO-free phase.
      Conclusions Oral SBI is safe and well tolerated at the doses studied in HIV
      patients with chronic diarrhea. No conclusions could be drawn regarding impact on
      GI symptoms. Additional studies are ongoing to examine the biological and
      immunologic effects of SBI in virologically suppressed HIV-infected patients.

PMID- 29210628
TI  - Editorial: Renin-Angiotensin System: Role in Chronic Diseases.

PMID- 29210627
TI  - Pharmacokinetic analysis of nevirapine extended release 400 mg once daily vs
      nevirapine immediate release 200 mg twice daily formulation in treatment-naive
      patients with HIV-1 infection.
AB  - BACKGROUND: VERxVE data showed non-inferior virologic efficacy with extended
      release nevirapine (NVP-XR) dosed 400 mg once daily (QD) versus immediate release
      nevirapine (NVP-IR) 200 mg twice daily in a double-blind, non-inferiority study
      in treatment-naive HIV-1-positive patients. OBJECTIVE: To study the
      pharmacokinetics (PK) of the NVP formulations and identify possible associations
      with demographic factors. METHODS: Patients with viral load >=1000 copies/mL and
      CD4+ count > 50- <400 cells/mm3 (males) and >50- <250 cells/mm3 (females) at
      screening received NVP-IR 200 mg QD during a 14-day lead-in and were then
      stratified by baseline viral load and randomized to NVP-XR or -IR. NVP trough
      concentrations at steady state (SS) (Cpre,ss,N) were measured up to week 48 for
      all participating patients. In a PK sub-study, SS parameters - AUC0-24, Cmax,
      Cmin, and peak-to-trough fluctuation were obtained and analyzed with relative
      bioavailability assessed at week 4 by plasma collection over 24 h. RESULTS:
      Trough concentrations were stable from week 4 to week 48 for all patients (n =
      1011) with both formulations, with NVP-XR/IR ratios of 0.77-0.82. Overall, 49
      patients completed the PK sub-study: 24 XR and 25 IR. NVP-XR showed less peak-to
      trough fluctuation (34.5%) than IR (55.2%), and lower AUC0-24, Cmin, Cmax, and
      trough concentrations than IR. However, no effect of SS trough concentrations was
      found on the virologic response proportion at least up to 1000 ng/mL. No
      significant association was found between NVP PK and gender, race, and viral
      load. CONCLUSION: These data suggest NVP-XR achieves lower but effective NVP
      exposure compared with NVP-IR.

PMID- 29210629
TI  - Development of a Substrate Identification Method for Human Scp1 Phosphatase Using
      Phosphorylation Mimic Phage Display.
AB  - BACKGROUND: Protein phosphorylation is strictly regulated by protein kinases and
      protein phosphatases, and disordered regulation of protein phosphorylation often
      causes serious diseases, such as cancer. Protein phosphatases are divided into
      two major groups: tyrosine (Tyr) phosphatases and serine/threonine (Ser/Thr)
      phosphatases. Substrate trapping mutants are frequently used to characterize Tyr
      phosphatases and identify their substrates; however, a rapid and simple method to
      identify substrates for Ser/Thr phosphatases has yet to be developed. Recently it
      has reported that AlF4 -/AlF3 and BeF3 - form a complex with Mg2+ in the
      catalytic center of FCP/SCP phosphatases, and that the Mg2+-AlF4 -/AlF3 complex
      mimics the transition state of the hydrolysis step, while the Mg2+-BeF3 - complex
      mimics the aspartylphosphate intermediate. OBJECTIVES: The main objective of this
      study was to develop a novel methodology, termed Phosphorylation Mimic Phage
      Display (PMPD), to identify substrates for Ser/Thr phosphatase Scp1 using peptide
      phage display libraries with Mg2+ and AlF4 -. METHODS: Recombinant protein of
      human full-length Scp1 (rScp1) expressed in E. coli system was purified by Co2+
      chelated affinity column, and then confirmed by SDS-PAGE and Western-blot
      analysis. The Ph.D.-C7C or M12 Phage Display Libraries (New England BioLabs,
      Beverly, MA) were screened using purified rScp1 immobilized on ELISA plate. Then,
      the plate was blocked with 0.5% (w/v) BSA in maleate buffer at 4 degrees C for 3
      h, before adding approximately 1*1010 plaque-forming units (pfu) of the phages in
      maleate blocking AlF4 - buffer to each well. After incubating, the wells were
      washed with maleate AlF4 - buffer to remove unbound phages. Then, phages were
      eluted with Mg2+ and AlF4 - free maleate buffer or with excess rScp1. After the
      third round of screening, the isolated phages were sequenced and subjected to
      binding analyses. RESULTS: After panning by PMPD method, 46 and 60 clones were
      isolated from the Ph.D. C7C and Ph.D. 12 phage libraries, respectively, as Mg2+
      or/and AlF4 - -dependent binding clones. The binding analyses showed that M12-1
      and Dep-3 specifically bind to Scp1 in an AlF4 --dependent manner. Notably, the
      Dep-3 peptide contained a Thr-Pro-Met-Ser sequence, which is similar to the Ser2
      Pro3-Thr4-Ser5 (Ser/Thr-Pro-partially hydrophobic residue-Ser) sequence found in
      CTD, which is an endogenous substrate for Scp1. Binding analyses also showed that
      both BP-14 and M12-6a bound to Scp1 in a Mg2+-dependent manner. BP-14 peptide
      contained Ser- Thr-Tyr and Pro-Phe-Glu sequences, which are similar to the Ser
      Thr-Trp and Ile-Phe-Glu sequences found in M12-6a, suggesting that one or both of
      these tripeptides may be the binding motif(s) recognized by Scp1. CONCLUSION: We
      developed a substrate identification method for the Ser/Thr phosphatase Scp1
      using a novel phage display method with AlF4 -. Dep-3 showed a core sequence
      similar to that of the CTD of RNA polymerase II, an endogenous Scp1 substrate,
      suggesting that this method is applicable for identifying novel Scp1 substrate
      candidates. This method will also be applicable for other FCP/SCP-type
      phosphatases, allowing us to better understand the substrate recognition
      mechanisms of Ser/Thr phosphatases.

PMID- 29210630
TI  - Use of a Phage-Display Method to Identify Peptides that Bind to a Tin Oxide
      Nanosheets.
AB  - BACKGROUND: Nanosheets of SnO2 which an n-type semiconductor with a rutile-type
      crystalline structure are predominantly used as gas sensors. SnO2 nanosheets have
      a tetragonal crystal structure where growth along the c-axis is suppressed to
      form a sheet. The major exposed facets of SnO2 nanosheets have {110}, {101} and
      {211} crystal planes along the a-axis, with the reduced {110} surface having a
      particularly high surface energy. Identifying peptides that bind to specific
      crystal planes by using peptide phage-display approach will increase the
      potential applications of metal oxide nanomaterials by fusing proteins with
      desirable active sites to peptides that adsorb at high density on the major
      exposed crystal plane of nanosheets. It may be possible to construct highly
      sensitive biosensors. OBJECTIVES: The main objective of the present study is to
      identify peptides that adsorb preferentially to a SnO2 nanosheet by using peptide
      phage display approach. METHODS: Four milligrams of SnO2 nanosheet were mixed
      with 1011 plaque-forming units of Ph.D.-12 Phage Display Peptide Library. Phage
      bound nanosheet particles were washed 10 times with 1 mL of phosphatebuffered
      saline containing 0.5% Tween 20. Phages bound to the nanosheet were eluted with
      three different buffers: (1) high-salt buffer containing 2 M NaCl (pH 7.5); (2)
      acidic buffer containing 200 mM Gly-HCl (pH 2.2); and (3) high-phosphate-ion
      buffer containing 500 mM NaH2PO4 (pH 7.5). The eluted phages were subjected to
      four or five rounds of biopanning. At each round, individual plaques were picked
      from the plates, and the amino acid sequences of the peptides were identified by
      DNA sequencing. The identified SnO2-binding peptides labeled with fluorescein
      isothiocyanate were synthesized. Adsorption isotherms were constructed at peptide
      concentrations ranging from 0.25 to 2.0 uM with 4mg of nanomaterials. RESULTS: We
      were determined the sequences of 11 clones with the high-salt buffer, 7 with the
      high-phosphateion buffers, and 6 with the acidic buffer and three peptides
      (SnO2BPn1, 2, and 3), two peptides (SnO2BPa1 and SnO2BPa2), and one peptide
      (SnO2BPp1) concentrated under each condition were selected respectively. All six
      selected peptides contained at least one histidine residue. In addition, the His
      Asn-Leu (HNL) sequence was found in two of the peptides (SnO2BPa1 and SnO2BPa2).
      We constructed adsorption isotherms for the six selected peptides using 4mg of
      nanosheets. All six peptides were well adsorbed on the SnO2 nanosheet. The
      adsorption isotherms for SnO2 material with different structure revealed that
      SnO2BPn1, -2, and -3, and SnO2BPp1, preferentially bound to the spherical SnO2
      nanoparticles. SnO2BPa2 preferentially bound to the SnO2 nanosheet, and SnO2BPa1
      bound equally to both materials. This result suggested that SnO2BPa2 bound to a
      specific crystal plane of the nanosheet. The major exposed facet of the SnO2
      crystal was the {110} plane, suggesting that SnO2BPa2 likely adsorbed on the
      {110} plane. SnO2BPn1, SnO2BPn2, SnO2BPn3, SnO2BPa1, and SnO2BPp1 also bound to
      the other metal oxides, in particular to ZrO2. At pH 7.5, peptides with a
      negative charge at pH 7.5 (pI 8.5-12) can bind to ZrO2 and SnO2, if the binding
      is mediated by electrostatic interactions. Thus, it is likely that these five
      peptides bind to metal oxides via electrostatic interactions. In contrast,
      SnO2BPa2 had a structurally specific affinity, binding more with the SnO2
      nanosheet than with the spherical SnO2 nanoparticles or other metal oxides.
      CONCLUSION: We identified six peptides that adsorbed on a SnO2 nanosheet. Five of
      the selected peptides bound preferentially to spherical SnO2 nanoparticles rather
      than to the SnO2 nanosheet. Whereas, SnO2BPa2 exhibited specifically binding to
      the SnO2 nanosheet. Our results suggest that crystal plane recognition and
      material recognition by these peptides are mediated via different, independent
      mechanisms.

PMID- 29210631
TI  - Uterine Function: From Normal to Polycystic Ovarian Syndrome Alterations.
AB  - BACKGROUND: The endometrium is one of the most important female reproductive
      organs. Polycystic ovarian syndrome (PCOS) is a reproductive and endocrine
      pathology that affect women of reproductive age. PCOS negatively affects the
      endometrium, leading to implantation failure and proliferative aberrations.
      METHODS: We conducted a search at the
      http://www.ncbi.nlm.nhi.gov/pubmed/electronic database using the following key
      words: endometrial steroid receptors, endometrium, uterine function, endometrium
      and PCOS, implantation window, implantation and PCOS, implantation markers,
      inflammation, oxidative stress. We selected the articles based on their titles
      and abstracts, then we analyzed the full text and classified the articles
      depending on the information provided according to the sections of the present
      review. RESULTS: The endocrine and metabolic abnormalities displayed in women
      with PCOS promote complex effects on the endometrium, leading to a low rate of
      implantation and even infertility. Women with PCOS show alterations in the
      Hypothalamic-Pituitary- Ovarian axis, which results in constant circulating
      levels of estrogen, similar to those at the early follicular phase, and a
      deficiency in the withdrawal of estrogen and progesterone. Besides this
      deficiency in the withdrawal of estrogen and progesterone, the insulin/ glucose
      pathway, adhesion molecules, cytokines and the inflammatory cascade, together
      with the establishment of a pro-oxidative status, lead to an imbalance in the
      uterine function, which in turn leads to implantation failure or even endometrial
      cancer. CONCLUSION: Women with PCOS display a dysregulation of the Hypothalamic
      Pituitary- Ovarian axis, which alters the steroid pathway. In addition, the
      deficiency in the withdrawal of estrogen and progesterone in the endometrium
      results in abnormal endometrial cellular proliferation. The imbalance in adipose
      tissue observed in PCOS patients reinforces the increase in circulating hormones.
      The present review describes the role of hormones, metabolites, cytokines,
      adhesion molecules and the insulin/glucose pathway related to the uterine
      endometrium in women with PCOS and their role in implantation failure and
      development of endometrial cancer.

PMID- 29210633
TI  - Recent Evidence on the Role of Dietary PUFAs in Cancer Development and
      Prevention.
AB  - BACKGROUND: Scientific evidence has been accumulated about the effects of
      polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3
      PUFAs might improve the efficiency of anticancer drugs has recently been
      considered. The role of n-6 PUFAs, in contrast, needs to be better assessed.
      However, the effective mechanisms of action of PUFAs have not been fully
      clarified yet. This review aims to report the most updated evidence on the role
      of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing
      on the potential mechanisms by which PUFAs exert their effects. METHODS: We
      undertook a structured search in PubMed on February 17th 2017 for peer-reviewed
      research articles published from 2013. The search syntax used was: PUFA or PUFAs
      and cancer. RESULTS: Contradictory results were found, most likely due to the
      genetic background, the different dietary sources used, the interaction among
      different nutrients, and the tumor subtypes. However, the more recent findings
      strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the
      other hand, n-6 PUFAs are often associated with an increased risk of cancer, even
      if recently their beneficial effects have also been highlighted. CONCLUSION: N-3
      PUFAs may represent a potential therapeutic agent contributing to treat at least
      some type of human cancers. However, studies with larger sample sizes and longer
      follow-up times are still needed. To increase the knowledge about how food and
      nutrition can improve human health it is advisable to deliver an open access
      nutritional database.

PMID- 29210632
TI  - Role of Matrix Metalloproteinases in Degenerative Kidney Disorders.
AB  - Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing
      endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling.
      MMPs are also known to cleave non-matrix proteins, including cell surface
      receptors, TNF-alpha, angiotensin-II, growth factors, (especially transforming
      growth factor-beta1, TauGF- beta1) plasminogen, endothelin and other bioactive
      molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the
      activity of MMPs and decrease ECM degradation. Various patho-physiological
      conditions have been linked with the imbalance of ECM synthesis and degradation.
      Numerous studies have reported the significance of MMPs and TIMPs in the
      progression of kidney pathologies, including glomerulonephritis, diabetic
      nephropathy, renal cancer, and nephrolithiasis. Although dysregulated activity of
      MMPs could directly or indirectly lead to pathological morbidities, their
      contribution in disease progression is still understated. Specifically, MMP
      activity in the kidneys and it's relation to kidney diseases has been the subject
      of a limited number of investigations. Therefore, the aim of the present review
      is to provide an updated insight of the involvement of MMPs and TIMPs in the
      pathogenesis of inflammatory and degenerative kidney disorders.

PMID- 29210634
TI  - Preventive and Therapeutic potentials of Anthocyanins in diabetes and associated
      complications.
AB  - Diet is an essential factor affecting the development of and risk for diabetes
      mellitus. In search of preventative and therapeutic strategies, it is to be
      considering the potential role of certain foods and their bioactive compounds to
      prevent the pathogenesis associated with metabolic diseases. Human consumption of
      anthocyanins is among the highest of all flavonoids. Epidemiological studies have
      suggested that the consumption of anthocyanins lowers the risk of diabetes and
      diabetic complications. Anthocyanins are important natural bioactive pigments
      responsible for red to blue colour of fruits, leaves, seeds, stems and flowers,
      which are present in a variety of plant species particularly in berries and
      cherries. A large number of bioactive anthocyanins, such as cyanidin, malvidin,
      delphinidin, pelargonidin, peonidin, petunidin and their metabolites have shown
      multiple biological activities with apparent effects on glucose absorption,
      glucose uptake, insulin secretion and sensitivity, on the enzymes involved in
      glucose metabolism, gene expressions, inflammatory mediators, glucose
      transporters in progression of diabetes and associated complications, such as
      diabetic retinopathy, nephropathy, neuropathy and diabetic vascular diseases. The
      versatility of the anthocyanins provides a promising approach for diabetes
      management than synthetic drugs. Here we summarize effect of several anthocyanins
      on many in vitro, in vivo and clinical studies and also reveals the mechanisms
      which could prevent or reverse the underlying mechanisms of diabetic pathologies
      including promotion of antioxidant, anti-hyperlipidemic, anti-inflammatory and
      anti-apoptotic activities.

PMID- 29210635
TI  - Potential drug targets in the pentose phosphate pathway of trypanosomatids.
AB  - The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp,
      are causative agents of important human diseases such African sleeping sickness,
      Chagas' disease and Leishmaniasis, respectively. The high impact of these
      diseases on human health and economy worldwide, the unsatisfactory available
      chemotherapeutic options and the absence of human effective vaccines, strongly
      justifies the search for new drugs. The pentose phosphate pathway has been
      proposed to be a viable strategy to defeat several infectious diseases, including
      those from trypanosomatids, as it includes an oxidative branch, important in the
      maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose
      5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic
      amino acids, are produced. This review provides an overview of the available
      chemotherapeutic options against these diseases and discusses the potential of
      genetically validated enzymes from the pentose phosphate pathway of
      trypanosomatids to be explored as potential drug targets.

PMID- 29210636
TI  - New insights into adipokines as potential biomarkers for type-2 diabetes
      mellitus.
AB  - A large number of studies have been focused on investigating serum biomarkers
      associated with risk or diagnosis of type-2 diabetes mellitus. In the last
      decade, promising studies have shown that circulating levels of adipokines could
      be used as a relevant biomarker for diabetes mellitus progression as well as
      therapeutic future targets. Here we discuss the possible use of recent described
      adipokines, including apelin, omentin-1, resistin, FGF-21, neuregulin-4 and
      visfatin, as early biomarkers for diabetes. In addition, we also include recent
      findings of other well know adipokines such as leptin and adiponectin. In
      conclusion, further studies are needed to clarify the pathophysiological
      significance and clinical value of these biological factors as potential
      biomarkers in type-2 diabetes and related dysfunctions.

PMID- 29210637
TI  - Metallopharmaceuticals in Therapy - A New Horizon for Scientific Research.
AB  - Coordination chemistry offers much scope for the design of novel and therapeutic
      agents, including metallopharmaceuticals. The widespread use of metal complexes
      as effective pharmaceuticals, e.g. cancer therapeutic, anti-inflammatory,
      antidiabetic drugs or antimicrobial and diagnostic agents, demonstrates that the
      cytotoxicity of metal ions can be finely controlled via the appropriate choice of
      ligands. The successful targeting of radioisotopes again depends on the ligand
      design and metal oxidation state. The complexes of platinum, ruthenium, cobalt,
      copper and other d-block metal ions have been used in medicine for a long time
      but only recent advances have been made in understanding the molecular basis of
      mechanism of their action. Due to the above mentioned purpose, we decided to
      prepare a detailed description of target-based research, directed towards a
      design and application possibilities, with the known mechanisms of action of
      metal ion complexes in the broad sense of therapy definition. The review also
      covers the progress, limitations and challenges of the above-mentioned approaches
      and emphasizes the advantages of well known and new metallopharmaceuticals in
      medicine and pharmacy.

PMID- 29210638
TI  - Medical applications of collagen and collagen-based materials.
AB  - Collagen and collagen-based materials have been successfully used in medicine for
      over 50 years. The number of scientific articles about the role of collagen in
      the construction of scaffolds for tissue engineering has risen precipitously in
      recent years. The review contains materials about historic and modern
      applications of collagen in medicine such as soluble collagen injections, solid
      constructs reconstructed from solution, and decellularized collagen matrices. The
      analysis of published data proves the efficacy of collagen material in the
      treatment of chronic wounds, burns, venous and diabetic ulcers, in plastic,
      reconstructive and general surgery, urology, proctology, gynecology,
      ophthalmology, otolaryngology, neurosurgery, dentistry, cardiovascular and bone
      and cartilage surgery, as well as in cosmetology. Further development of
      collagenoplasty requires addressing the problems of allergic complications,
      improvement of structure and maximizing therapeutic effects against pathological
      processes.

PMID- 29210639
TI  - Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology.
AB  - BACKGROUND: Guanylate cyclase C (GC-C) receptor is a transmembrane receptor,
      predominantly expressed in intestinal epithelial cells, which is considered to
      play a main role in homeostasis and function of the digestive tract. The
      endogenous ligands for this receptor are the paracrine hormones uroguanylin and
      guanylin. Upon ligand binding, GC-C receptors increase cyclic guanosine
      monophosphate (cGMP) levels, regulating a variety of key cell-type specific
      processes such as chloride and bicarbonate secretion, epithelial cell growth,
      regulation of intestinal barrier integrity and visceral sensitivity. It has been
      suggested that GC-C acts as an intestinal tumor suppressor with the potential to
      prevent the initiation and progression of colorectal cancer. In fact, loss of
      ligand expression is a universal step in sporadic colorectal carcinogenesis.
      Interestingly, the role of GC-C is not limited to the digestive tract but it has
      been extended to several other systems such as the cardiovascular system, kidney,
      and the central nervous system, where it has been involved in a gut-hypothalamus
      endocrine axis regulating appetite. Objetive: In this review we summarize the
      physiology of the GC-C receptor and its ligands, focusing on newly developed
      drugs like linaclotide, and their suggested role to reverse/prevent the diseases
      in which the receptor is involved. CONCLUSION: Available data points toward a
      relationship between uroguanylin and guanylin and their receptor and pathological
      processes like gastrointestinal and renal disorders, colorectal cancer, obesity,
      metabolic syndrome and mental disorders among others. Recent pharmacological
      developments in the regulation of GC-receptor may involve further improvements in
      the treatment of relevant diseases.

PMID- 29210640
TI  - Fine-tuning of microRNAs in type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a metabolic disease widely spread across
      industrialized countries. Sedentary lifestyle and unhealthy alimentary habits
      lead to obesity, boosting both glucose and fatty acid in the bloodstream and
      eventually, insulin resistance, pancreas inflammation and faulty insulin
      production or secretion, all of them very well-defined hallmarks of type 2
      diabetes mellitus. miRNAs, are small sequences of non-coding RNA that may
      regulate several processes within the cells, fine-tuning protein expression, with
      an unexpected and subtle precision and in time-frames ranging from minutes to
      days. Since the discovery of miRNA and their possible implication in pathologies,
      several groups aimed to find a relationship between type 2 diabetes mellitus and
      miRNAs. Here we discuss the pattern of expression of different miRNAs in cultured
      cells, animal models and diabetic patients. We summarize the role of the most
      important miRNA involved in pancreas growth and development, insulin secretion
      and liver, skeletal muscle or adipocyte insulin resistance in the context of type
      2 diabetes mellitus.

PMID- 29210641
TI  - Dynamic Localization of Hepatocellular Transporters: Role in Biliary Excretion
      and Impairment in Cholestasis.
AB  - Bile flow generation is driven by the vectorial transfer of osmotically active
      compounds from sinusoidal blood into a confined space, the bile canaliculus.
      Hence, localization of hepatocellular transporters relevant to bile formation is
      crucial for bile secretion. Hepatocellular transporters are localized either in
      the plasma membrane or in recycling endosomes, from where they can be relocated
      to the plasma membrane on demand, or endocytosed when the demand decreases. The
      balance between endocytic internalization/exocytic targeting to/from this
      recycling compartment is therefore the main determinant of the hepatic capability
      to generate bile, and to dispose endo- and xenobiotics. Furthermore, the
      exacerbated endocytic internalization is a common pathomechanisms in both
      experimental and human cholestasis; this results in bile secretory failure and,
      eventually, post-translational transporter downregulation by increased
      degradation. This review summarizes the proposed structural mechanisms accounting
      for this pathological condition (e.g., alteration of function, localization or
      expression of F-actin or F-actin/transporter cross-linking proteins, and switch
      to membrane microdomains where they can be readily endocytosed), and the
      mediators implicated (e.g., triggering of "cholestatic" signaling transduction
      pathways). Lastly, we discussed the efficacy to counteract the cholestatic
      failure induced by transporter internalization of a number of therapeutic
      experimental approaches based upon the use of compounds that trigger exocytic
      targetting of canalicular transporters (e.g., cAMP, tauroursodeoxycholate). This
      therapeutics may complement treatments aimed to transcriptionally improve
      transporter expression, by affording proper localization and membrane stability
      to the de novo synthesized transporters.

PMID- 29210642
TI  - Antidiabetics: Structural Diversity of Molecules with a Common Aim.
AB  - BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global
      proportions which is currently affecting 1 in 12 adults in the world, with still
      increasing prevalence. World Health Organization (WHO) declared this worldwide
      health problem, as an epidemic disease, to be the only non-infectious disease
      with such categorization. People with DMT2 are at increased risk of various
      complications and have shorter life expectancy. The main classes of oral
      antidiabetic drugs accessible today for DMT2 vary in their chemical composition,
      modes of action, safety profiles and tolerability. METHODS: A systematic search
      of peer-reviewed scientific literature and public databases has been conducted.
      We included the most recent relevant research papers and data in respect to the
      focus of the present review. The quality of retrieved papers was assessed using
      standard tools. RESULTS: The review highlights the chemical structural diversity
      of the molecules that have the common target-DMT2. So-called traditional
      antidiabetics as well as the newest and the least explored drugs include
      polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1,
      dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives,
      benzylthiazolidine- 2,4-diones (peroxisome proliferator activated receptor-gamma
      agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules
      (alpha-glucosidase and sodium/ glucose co-transporter 2 inhibitors). CONCLUSION:
      As diabetes becomes a more common disease, interest in new pharmacological
      targets is on the rise.

PMID- 29210643
TI  - Adipokines and Myokines: A Pivotal Role in Metabolic and Cardiovascular
      Disorders.
AB  - Obesity induces an imbalance in the expression and secretion of several
      cytokines, which contributes to the development of metabolic and cardiovascular
      disorders. On the contrary, skeletal muscle is known to have a role in reversing
      the detrimental impact of obesity. It has been established that adipose tissue
      acts as an endocrine organ that secretes proinflammatory and anti-inflammatory
      adipokines. Similarly, skeletal muscle produces secretory molecules, called
      myokines, from contracting muscle fibers. Myokines were recently recognized as
      beneficial modulators of obesity, metabolic syndrome, and type 2 diabetes.
      Furthermore, adipokines and myokines play a crucial role in the communication
      between adipose tissue, skeletal muscle and other organs. It could be beneficial
      to find novel adipokines and myokines, and to explore their signaling pathways to
      identify targets for the treatment and prevention of cardiometabolic disorders.
      In this review, we summarize recent studies on cross-talk between skeletal muscle
      and adipose tissue. In particular, we concentrate on the major action mechanisms
      of adipokines and myokines, such as adiponectin, adipocyte fatty acid binding
      protein, C1q/TNF-related proteins, interleukin- 6, irisin, and fibroblast growth
      factor 21.

PMID- 29210645
TI  - Editorial: Acting on Tat-Mediated Transcription to Achieve a Long Term Control of
      HIV-1 Latency.

PMID- 29210644
TI  - Carboxylesterase Inhibitors: An Update.
AB  - Mammalian carboxylesterases are key serine hydrolases that catalyze the
      hydrolysis of a wide variety of ester compounds in the corresponding carboxylic
      acids and alcohols. In human, two major carboxylesterases, CES1 and CES2, have
      been identified and well-studied over the past decade. CES1 inhibitors have
      potential applications in the treatment of hypertriglyceridaemia, obesity and
      type 2 diabetes, owing to that this enzyme plays prominent role in the metabolism
      of cholesteryl esters. CES2 plays crucial roles in the metabolic activation of
      many prodrugs including anticancer agents capecitabine and CPT-11. Co
      administration with CES2 inhibitors may ameliorate CPT-11 associated
      lifethreatening diarrhea or improve the half-lives of CES2-substrate drugs. The
      important roles of carboxylesterases in both endogenous and xenobiotic metabolism
      arouse great interest in the discovery and development of potent and selective
      inhibitors against these enzymes. This review is focused on the application
      potentials and recent advances in the discovery and development of
      carboxylesterases inhibitors. The inhibitory capacities and inhibition mechanism
      of a variety of carboxylesterases inhibitors including synthetic, semi-synthetic
      and natural compounds are comprehensively summarized. Furthermore, the key
      structural features and structure-activity relationships (SARs) of different
      classes of CES1 and CES2 inhibitors are discussed. All information and knowledge
      summarized in this review will be very helpful for the medicinal chemists to
      design and develop more potent and highly selective carboxylesterases inhibitors
      for potential biomedical applications.

PMID- 29210646
TI  - PCSK9 and Hypercholesterolemia: Therapeutic Approach.
AB  - Despite the intensive research and progress in modern pharmacotherapy,
      hypercholesterolemia and related cardiovascular complications remain one of the
      leading causes of mortality and disability in the modern world. A significant
      contribution to the treatment of hypercholesterolemia was made by the discovery
      of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is
      responsible for the degradation of the low-density lipoprotein (LDL) receptor
      (LDLR) found at the surface of the plasma membrane in the liver and directly
      associated with serum LDL level. Limitations in standard therapy used in the
      treatment of lipid disorders have led to the development of new drugs, such as an
      inhibitor of PCSK9. Over the past years, the greatest achievement in discovering
      the PCSK9 inhibitor was made by designing monoclonal antibodies that disable
      PCSK9 to bind LDLR and RNA interference to reduce PCSK9 production, but one of
      the main disadvantages is costeffectiveness. In this review, we will summarize
      the most recent findings of basic and clinical studies which focus on PCSK9
      function, regulation and therapeutic target for the treatment of
      hypercholesterolemia and associated cardiovascular diseases.

PMID- 29210647
TI  - alpha-Mangostin, A Natural Xanthone, Induces Apoptosis and ROS Accumulation in
      Human Rheumatoid Fibroblast-Like Synoviocyte MH7A Cells.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a complicated and heterogeneous chronic
      disease with the characteristic of progressive joint destruction, deformity and
      disability. It is associated with not only genetic but also environmental
      factors. Many studies suggest that RA-derived fibroblast-like synoviocyte (RA
      FLS) is involved in the pathogenic process of RA. The apoptosis and proliferation
      of RA-FLS is of great importance in the development and progression in RA.
      Nowadays, more and more traditional Chinese medicine (TCM) or natural products
      are studied in the treatment of RA. OBJECTIVE: To investigate the effects of
      several natural products and the apoptosisinduced effect of alpha-mangostin and
      its underlying mechanisms in RA-FLS MH7A cells. METHODS: The effects of natural
      products on MH7A cells were detected by MTT assay. Annexin V-FITC/PI double
      labeling and DAPI staining were adopted to observe the apoptosis induced by alpha
      mangostin. The apoptosis related proteins were measured with western blotting
      analysis. ROS accumulation was determined by DHE staining. RESULTS: Xantones,
      including Garcinone C, alpha-mangostin and gamma-mangostin, significantly
      inhibited the MH7A cell viability. And alpha-mangostin induces apoptosis in MH7A
      cells. Further study showed that alpha-mangostin increased the ratio of Bax/Bcl-2
      and increased the ROS generation in MH7A cells. CONCLUSION: alpha-Mangostin
      induces the apoptosis of MH7A cells through increasing ROS accumulation and the
      ratio of Bax/Bcl-2, suggesting that alpha-mangostin should be benefit to the
      therapy of RA.

PMID- 29210648
TI  - Vitamins for Cancer Prevention and Treatment: An Insight.
AB  - Over a few decades a strong interlink between oxidative damage and cancer has
      been investigated by various scientists across the world on the basis of
      epidemiological observations of the effects of fruits and vegetables used in the
      diet for cancer patients. Primarily, Vitamin C, Vitamin D and Vitamin E are
      reported to be involved in the amelioration of side effects which occur in
      chemotherapy and radiation therapy of lungs, stomach, prostate, colorectal,
      gastric head and neck cancers. The vitamins acting as antioxidant adjuvants are
      found to have apoptotic and antiangiogenesis potential as well as inhibitory
      effects against metastasis in cancer cells. This chapter explicitly discusses the
      key aspects concerned with the vitamins in relation to cancer prevention and
      treatment. It describes vitamins and their natural resources, role of vitamins in
      the body, and vitamins as prime ingredients in the diet and their effects on
      cancer biology with reference to recent research reports. Moreover, this paper
      also includes the emerging potential of pharmaceutical advances to enhance
      bioavailability of the vitamins to cancer patients with improved safety and
      efficacy. Clinicians and researchers must mull over the nutritional requirements
      of individual cancer patient so as to treat cancer and increase life expectancy.

PMID- 29210649
TI  - Sargassum fusiforme Polysaccharide Rejuvenat es the Small Intestine in Mice
      Through Altering its Physiol ogy and Gut Microbiota Composition.
AB  - BACKGROUND AND OBJECTIVE: Aging can result in a progressive decline in cellular
      protection and physiological function. The physiological status and microbiota of
      the intestine are intensively linked to the aging process. Numerous studies have
      suggested that Sargassum fusiforme polysaccharides possess antioxidant and
      antiaging activities. However, it remains unclear as to whether S. fusiforme
      polysaccharides can prevent the insult of oxidant and aging through modulating
      the physiological status and microbiota of the intestine. METHODS: To assess the
      cytoprotective effect of S. fusiforme polysaccharides (SFPS) in the small
      intestine of mice embarking on the aging process, we compared the expressions of
      Nrf2 and several representative markers (SOD-2, CAT, NQO1 and HO-1) of the
      Nrf2/ARE signaling pathway in the small intestine of male ICR mice fed with a
      control diet with those of mice fed with a SFPS-containing diet. In addition, the
      overall compositional changes in the small intestine microbiota were determined
      by 16s rDNA sequencing followed by alpha and beta diversity analyses. RESULTS:
      The results showed that dietary intake of SFPS could ameliorate the declined
      cytoprotective capacity of the small intestine by upregulating the Nrf2/ARE
      signaling pathway. Moreover, SFPS could partially rejuvenate the overall status
      of the small intestine microbiota. CONCLUSION: The results suggested that dietary
      SFPS may promote the health condition of the small intestine, consequently
      leading to a healthy aging.

PMID- 29210650
TI  - Reprograming Carcinoma Associated Fibroblasts by microRNAs.
AB  - Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during
      development of several cancer types, and therefore emerge as an attractive
      therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that
      block the functions of CAFs have already been in clinical trials. However, these
      drugs exhibit limited efficacy in patients, partially due to the fact that
      currently used biomarkers for determining efficacy are not CAF-specific.
      Furthermore, depletion of CAFs may promote carcinogenesis and accelerate cancer
      progression by inducing immunosuppression and hypoxia, leading to reduced
      survival. Accumulating evidence demonstrates that restoring the expression of key
      microRNA induces the functional conversion of CAFs into normal fibroblasts by
      targeting different signaling pathways and metabolic mechanisms. Therefore,
      reprograming CAFs into normal fibroblasts by altering specific expression of
      microRNAs, rather than targeted ablation, may be an effective, novel strategy for
      cancer treatment. This review focuses on specific microRNAs involved in the
      transformation of CAFs as well as their multiple roles during tumorigenesis and
      chemo-resistance.

PMID- 29210652
TI  - Inhibition of JAK2 Signaling Alleviates Hyperlipidemia-Intensified Caerulin
      Induced Acute Pancreatitis In Vivo.
AB  - RATIONALE: Studies have implied the positive association of JAK2/STAT3 signaling
      with the onset and severity of acute pancreatitis (AP). However, definitive
      functional study of JAK2/STAT3 signaling in the pathogenesis of acute
      pancreatitis in vivo is missing and its potential as a therapeutic target and the
      underlying mechanisms remain to be determined. OBJECTIVES: The aim of this study
      was to explore the role of JAK2/STAT3 signaling in the pathogenesis of
      hyperlipidemia-intensified caerulin-induced AP and its potential as a therapeutic
      target. METHODS AND RESULTS: Using the caerulin-induced acute pancreatitis rat
      model, we showed that JAK2/STAT3 signaling was activated in pancreas and systemic
      inflammation was increased during AP. Pharmacological suppression of JAK2 by its
      inhibitor AG490 robustly protected against tissue damage, attenuated JAK2/STAT3
      signaling and inflammatory responses. Local pancreatic tissue damage and phosphor
      JAK2 in the pancreatic tissue were enhanced in animals fed with high fat diet
      compared to chow-diet fed animals. Interestingly, JAK2 inhibitor AG490
      significantly inhibited pancreas necrosis and systemic inflammation in animals
      fed with high fat or chow-diet, but did not affect STAT3 signaling. CONCLUSION:
      These results establish that JAK2 activation plays a significant role in the
      pathogenesis of caerulin-induced AP in animals on both chow and high-fat diets by
      regulating necrosis and systemic inflammation. Thus, our results not only clarify
      novel signaling mechanisms in AP but also suggest that JAK2 might constitute a
      target in the management of hyperlipidemia-intensified caerulin-induced AP.

PMID- 29210651
TI  - miR-25 Mediates Retinal Degeneration Via Inhibiting ITGAV and PEDF in Rat.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the main cause of
      irreversible blindness in the elderly. Oxidative stress in retinal pigment
      epithelium (RPE) is deemed to play a pivotal role in the pathogenesis of AMD. miR
      25 functions as an essential modulator in response to oxidative-stress in several
      cell types, but its function in RPE cells is poorly understood. OBJECTIVE: To
      explore the roles of miR-25 in RPE cells and in the development of AMD. METHODS:
      A rat model of retinal degeneration was induced by sodium iodate (SI). Subretinal
      injection of antagomiR-25 was performed for the intervention while the scramble
      as control. Visual responses were recorded with Electroretinogram (ERG). TUNEL
      assay was performed to detect apoptosis. Phagosome quantification in vivo was
      performed to evaluate RPE cell function. Oxygen-glucose deprivation treatment was
      performed to mimic in vitro oxidative stress. Gene expression at mRNA level and
      protein level were performed by quantitative polymerase chain reaction (qPCR) and
      Western Blot, respectively. The pigment epithelium derived factor (PEDF) level in
      the cultured medium was measured by Enzyme-linked immunosorbent assay (ELISA).
      The interaction between miR-25 and integrin alphaV (IGTAV) / PEDF 3'UTR was
      examined by dual luciferase assay. Chromatin immunoprecipitation (ChIP) assay was
      performed to examine its transcriptional regulation of miR-25. RESULTS: Oxidative
      stress up-regulated miR-25 in RPE cells in very early stage, accompanied by
      decreased phagocytosis and reduced growth factor secretion in those cells. Such
      changes preceded RPE cell apoptosis and visual impairment in the SItreated rats.
      Furthermore, antagomiR-25 intervention effectively rescued RPE cells from
      degeneration in such model. The increased miR-25 was confirmed to mediate RPE
      degeneration through direct targeting IGTAV and PEDF. On the other hand,
      upstream, miR-25 was found to be up-regulated by STAT3 signaling under oxidative
      stress in both in vivo and in vitro models. CONCLUSION: Our findings demonstrate
      that, in SI-treated rats, oxidative stress activates STAT3 signaling which up
      regulates miR-25 expression, in a very early stage. The increased miR-25 then
      inhibits ITGAV and PEDF expressions, resulting in RPE phagocytosis dysfunction
      and then RPE apoptosis and visual impairment as observed in patients with AMD.
      These findings lead us to a better understanding of AMD pathogenesis, and suggest
      that miR-25 could be a potential therapeutic target for oxidative stress related
      RPE diseases, like AMD.

PMID- 29210653
TI  - Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference
      in Cell Biology and Effects on Retinal Degeneration in RCS Rats.
AB  - BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential
      candidates for treating retinal degeneration (RD). OBJECTIVE: To further study
      the biology and therapeutic effects of the hUC-MSCs on retinal degeneration.
      METHODS: Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated
      by single-cell cloning method and their therapeutic functions were compared in
      RCS rat, a RD model. RESULTS: Although both subsets satisfied the basic
      requirements for hUC-MSCs, they were significantly different in morphology,
      proliferation rate, differentiation capacity, phenotype and gene expression.
      Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1
      displayed stronger colony forming potential as well as adipogenic and osteogenic
      differentiation capacities. When the two subsets were respectively transplanted
      into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1
      expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1
      showed stronger rescue effect on the retinal function as indicated by the higher
      b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased
      apoptotic photoreceptors. When both subsets were treated with interleukin-6,
      mimicking the inflammatory environment when the cells were transplanted into the
      eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic
      factors in comparison with hUC-MSC2. CONCLUSION: The data here, in addition to
      prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic
      effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect,
      paracrine of trophic factors and potential RPE cell differentiation capacity.
      Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should
      be used for effective treatment of RD.

PMID- 29210655
TI  - Editorial: Recent News on Statins for the Treatment of Non-Alcoholic Fatty Liver
      Disease/Non-Alcoholic Steatohepatitis.

PMID- 29210656
TI  - Editorial: Arterial Stiffness, Central Haemodynamics and Non-Alcoholic Fatty
      Liver Disease: Links with Cardiovascular Risk and Effects of Drug Treatment.
AB  - Arterial stiffness, central haemodynamics and Non-Alcoholic Fatty Liver Disease
      (NAFLD) have been associated with increased risk for Cardiovascular (CV)
      morbidity and mortality. Antihypertensive, antidiabetic and hypolipidaemic drugs
      may affect these predictors of CV risk. Such associations should be taken into
      consideration when treating high-risk patients.

PMID- 29210654
TI  - Glaucoma and Alzheimer Disease: One Age-Related Neurodegenerative Disease of the
      Brain.
AB  - BACKGROUND: Open Angle Glaucoma (POAG) is the leading causes of irreversible
      blindness worldwide. Elevated intraocular pressure is considered an important
      risk factor for glaucoma; however, a subset of patients experiences a progression
      of the disease even in presence of normal intraocular pressure values. This
      implies that risk factors other than intraocular pressure are involved in the
      pathogenesis of glaucoma. A possible relationship between glaucoma and
      neurodegenerative diseases such as Alzheimer Disease has been suggested. In this
      regard, we recently described a high prevalence of alterations typical of
      glaucoma, using Heidelberg Retinal Tomograph-3, in a group of patients with
      Alzheimer Disease. Interestingly, these alterations were not associated with
      elevated intraocular pressure or abnormal Central Corneal Thickness values.
      Alzheimer Disease is the most common form of dementia with progressive
      deterioration of memory and cognition. Complaints related to vision are common
      among Alzheimer Disease patients. METHODS: In this paper researches related to
      glaucoma and Alzheimer disease are reviewed. RESULTS: Diseases characteristics,
      i.e. common features, risk factors and pathophysiological mechanisms gathered in
      the recent literature do suggest that Alzheimer Disease and glaucoma can be
      considered both age-related neurodegenerative diseases that may co-exist in the
      elderly. CONCLUSION: In conclusion, preclinical and clinical evidence gathered so
      far support the notion that glaucoma is a widespread neurodegenerative condition
      whose common pathogenetic mechanisms with other diseases, i.e. Alzheimer Disease,
      should be further investigated as they may shed new light on these diseases
      improving both diagnosis and treatments.

PMID- 29210657
TI  - Diabetes and Atherosclerosis: Old Players in a New Field, Osteoporosis.

PMID- 29210658
TI  - Matrix Metalloproteinases as Markers of Atherosclerosis in Renal Patients: Are we
      there Yet?

PMID- 29210659
TI  - beta-Adrenergic Receptor Gene Polymorphisms and its Relationship with Heart
      Failure.

PMID- 29210660
TI  - Host Factor Predictors in Long-term Nonprogressors HIV-1 Infected with Distinct
      Viral Clades.
AB  - BACKGROUND: HIV-1+ long-term nonprogressors (LTNPs) maintain natural control of
      viral infection. This study sought to identify and characterize HIV- LTNPs series
      case, regarding the presence of possible host factors that may be associated with
      this status. METHODS: We evaluated the plasma levels of IP-10/IL-8 chemokines,
      HLA-B alleles, and IL28B rs12979860 polymorphism in 24 LTNPs who presented with
      infection by different clades of HIV-1. RESULTS: IL-8 chemokine was significantly
      higher in progressors than in LTNPs, but there was no difference between the LTNP
      subgroups. There was a negative correlation in CD4+ T cell (TC) count and IL-8
      dosage, and a positive correlation with CD8+ TC. IP-10 chemokine levels were
      associated with viremia, and the elite controller (EC) subgroup showed nearly the
      same level than healthy individuals and progressors with viral load suppressed.
      Furthermore, the CD4+ TC count, percentage of CD4+ TC, and CD4/CD8 ratio were
      negatively correlated with IP-10. No association was found in plasma levels of IL
      8 and IP-10 chemokines and HIV-1 clades. In the EC/viremic controller subgroup,
      80% presented with at least one HLA-B allele previously considered as potentially
      protective for AIDS progression. No association was observed between the HLA-B
      alleles and HIV- 1 clades. The IL28B CC genotype was identified in 87.5% of
      LTNPs. CONCLUSION: In this LTNP series case we observed different host factors
      that may be contributing to their nonprogressor status, and the association of
      these factors with the control of infection progression may be critically
      important for future therapeutic and prophylactic options in HIV-1 infection.

PMID- 29210662
TI  - Response to Doxorubicin of Exfoliated Human Buccal Epithelium Cells: Comparison
      of Three Methods of Cell Staining and Calcium Assessment.
AB  - BACKGROUND: Doxorubicin is an anthracycline antibiotic which inhibits DNA and RNA
      synthesis intercalating DNA double helix and inducing free radicals. Doxorubicin
      is used in the treatment of cancer diseases. The influence of Doxorubicin on
      human buccal cell was used as a model for the assessment of toxic effects in
      vitro. OBJECTIVE: We studied the possibility of using the process of
      heterochromatinization in cell nuclei in toxicological investigations of drugs in
      vitro. METHOD: The exfoliated buccal epithelium cells of two donors (men) - Donor
      A (24 years) and Donor B (23 years) were used. Cells were subjected to
      Doxorubicin in concentration 0.2; 2; 20, and 200 ug/ml for 2 h. RESULTS: A
      significant increase of chromatin condensation in a dose-dependent way was shown.
      Doxorubicin induced chromatin condensation for cells of donors A and B if >= 0.2
      ug/ml, and >= 2 ug/ml, correspondingly. Cell viability assessed by combined
      staining with Hoechst 33342 and ethidium bromide revealed a significant increase
      of damaged cells if >= 2 ug/ml. Indigo carmine staining also revealed a
      significant increase in permeability of cell membranes if >= 20 ug/ml. In cells
      of donor A the intranuclear calcium concentration increased if Doxorubicin
      concentration was >= 0.2 ug/ml. In cells of donor B cytoplasmic and intranuclear
      calcium concentration decreased if Doxorubicin concentration >= 0.2 ug/ml.
      CONCLUSION: The comparison revealed high sensitivity of the method of chromatin
      changes registration in human buccal epithelium cells as a method of assessment
      of drug toxicity in vitro, and this method may be recommended for toxicological
      investigations.

PMID- 29210661
TI  - Impact of Different Antiretroviral Strategies on Total HIV-DNA Level in
      Virologically Suppressed HIV-1 Infected Patients.
AB  - BACKGROUND: Total HIV-DNA load in peripheral blood cell (PBMCs) reflects the
      global viral reservoir that seems not to be affected by antiretroviral treatment.
      However, some studies reported a different permeability of different drugs in
      cellular compartments. OBJECTIVE: To investigate the relation between the amount
      of total HIV-1 DNA and different treatment strategies. METHODS: Total HIV-1 DNA
      was quantified by real time PCR in PBMCs collected from 161 patients with long
      term undetectable HIV-RNA receiving different therapy schedules (3-drug regimens
      or 2-drug regimen containing Raltegravir as integrase inhibitor). RESULTS:
      Overall, HIV patients who started therapy with a median pre-ART CD4+ cell count
      >400 cells/mm3 and HIV viral load of 3 log10 copies/ml, achieved a lower amount
      of HIV total DNA. No significant correlation was found in DNA size when patients
      were stratified on the basis of different therapeutic protocols. However, HIV DNA
      load analysis, when only performed in HIV patients with a median pre-ART CD4+
      cell count >200 cells/mm3 and HIV viral load < 3 log10 copies/ml, showed a
      significative DNA decrease in Raltegravir treated group with respect to the
      NNRTIs-treated group. CONCLUSION: The data emphasize that HIV-DNA level
      represents a predictive factor in long-term suppressive therapy patients. In
      addition, the diminished reservoir, only observed in patients treated with the
      NRTI-sparing regimen RAL plus PI/r before immunological and virological
      derangement, suggests that latest generation drugs, such as integrase inhibitors,
      might represent an optimal chance in the management of HIV infection.

PMID- 29210663
TI  - DNA Methylation: A Frontier in Tooth Organogenesis and Developmental Dental
      Defects.
AB  - BACKGROUND: Tooth development relies on interactions between epithelial and
      mesenchymal tissues, which are controlled by sophisticated networks of conserved
      signaling. The signaling networks regulating odontogenesis have been well
      characterized, but the epigenetic mechanisms underlying remain to be elucidated.
      OBJECTIVE: In this review, we describe current researches regarding the control
      of various genes expression by DNA methylation during odontogenesis, summarize
      genomic mapping of DNA methylation in various stages of tooth formation and
      diverse dental tissues by high-throughput approaches, and highlight the roles of
      DNA methylation in odontogenesis. RESULTS: Researches on mammals have revealed
      that the genomic methylation, which occurs on cytosine residues, regulates
      certain genes transcription. Consequently, DNA methylation plays a crucial role
      in spatiotemporal organization of signaling pathways, and is essential for
      organogenesis. Recently, mounting evidence proves that methylation of genomes
      contributes to the spatiotemporal gene dynamics during odontogenesis. With
      emerging new technologies of mapping cytosine modifications in global genome,
      investigators are seeking an overall view of DNA methylome dynamics that
      characterize genetic information to manifest across incredibly varied tooth
      development stages, dental tissues, and developmental dental defects.

PMID- 29210664
TI  - Advances in the Discovery of Anthraquinone-Based Anticancer Agents.
AB  - BACKGROUND: The anthracene-9,10-dione (anthraquinone) derivatives represent an
      exceptionally valuable class in anticancer drug development. An outstanding
      antitumor potency of the anthracycline antibiotics attracted the attention of
      medicinal chemists since the discovery of these chemotypes. The prominent
      anthraquinone-based drugs doxorubicin, mitoxantrone as well as more recent
      epirubicin, idarubicin, and valrubicin are successfully used in chemotherapy of
      hematological malignancies and solid tumors. The anthraquinone core remains a
      promising scaffold for the search of new optimized drug candidates. OBJECTIVE: In
      this study, we analyze the progress in discovery and development of antitumor
      anthracene- 9,10-diones based on patent and journal publications in 2008-2017.
      The main goal is to dissect novel chemotypes of anthraquinone derivatives; other
      important issues such as the success in bioconjugate chemistry of anthraquinone
      containing agents as well as the patents on new applications of anthracyclines
      are beyond the scope of this review. CONCLUSION: A number of newly discovered
      natural products, the perspective directions for chemical modifications to
      optimize the anticancer properties, and novel intracellular targets demonstrate
      that anthracene- 9,10-diones deserve further in-depth investigation as an
      important source of drug candidates.

PMID- 29210665
TI  - Synthesis and Evaluation of a New Series of Arylidene Indanones as Potential
      Anticancer Agents.
AB  - BACKGROUND: Arylidene indanones have attracted a great deal of interest due to
      their outstanding therapeutic applications. In particular, considerable research
      has pointed out the importance of arylidene indanones in the field of cancer
      research. OBJECTIVE: The aim of the current work was to design and synthesize
      arylidene indanone-based anticancer agents. METHOD: New arylidene indanones were
      obtained via the Claisen-Schmidt condensation of 5-chloro-6-methoxy-2,3-dihydro
      1H-inden-1-one with p-substituted benzaldehyde derivatives. MTT assay was
      performed to evaluate their cytotoxic effects on MCF-7 human breast
      adenocarcinoma, HeLa human cervix carcinoma and NIH/3T3 mouse embryonic
      fibroblast cell lines. The most effective derivatives were evaluated for their
      DNA synthesis inhibitory and apoptotic effects. The most apoptotic compounds were
      also investigated for their effects on caspase-3 activation in HeLa cells.
      RESULTS AND CONCLUSION: Compounds 2, 3, 4, 5, 6 and 7 exhibited selective
      anticancer activity against HeLa cells, whilst compounds 7 and 10 showed
      selective anticancer activity against MCF-7 cells. Compound 10 caused significant
      DNA synthesis inhibition on MCF-7 cells, whereas compound 3 caused significant
      DNA synthesis inhibition on HeLa cells. Compounds 2 and 3 were determined as the
      most apoptotic agents against HeLa cells, whereas compounds 7 and 10 showed
      apoptotic activity against MCF-7 cells. Besides, compound 2 was identified as the
      most effective compound on caspase-3 activation in HeLa cells. The binding
      interactions of compound 2 at the active site of caspase-3 were confirmed through
      molecular docking studies. Docking studies showed that compound 2 interacted with
      the residues His121 and Tyr204 forming pi-pi stacking interactions.

PMID- 29210666
TI  - A Newly Synthetized Ferrocenyl Derivative Selectively Induces Apoptosis in ALL
      Lymphocytes through Mitochondrial Estrogen Receptors.
AB  - BACKGROUND: Estrogens, as the main female steroid hormones have multiple proven
      effects on reproductive and non- reproductive systems. Expression of ERalpha and
      ERbeta, two dominant estrogen receptors, in peripheral blood mononuclear cells in
      certain B-cell malignancies and the existence of estrogens receptors on
      mitochondria is open to question that estrogen likely has an impact on the
      cancerous lymphocytes life span. Acute lymphoblastic leukemia (ALL) is the
      frequent pediatric malignity which is recurrent and hardly curable in many cases.
      The malignant cells are generally resistant to apoptosis caused the severe
      lymphocytes accumulation in the peripheral blood. METHODS: By focusing on
      mitochondria as a life/death center of the cell; in the current research we
      compared cytotoxicity effects of a new ferrocenyl derivative with raloxifene as
      well-known SERMs considering the apoptotic process and survival of cancerous
      lymphocytes. RESULTS: We demonstrated that both ferrocenyl derivative and
      raloxifene could cause mitochondrial lesion and initiate the apoptosis process by
      caspase activation and cytochrome c release. CONCLUSIONS: In brief, the
      ferrocenyl derivative could induce estrogen-related selective apoptosis on
      cancerous lymphocytes by affecting mitochondrial receptors.

PMID- 29210667
TI  - Nerolidol and its Pharmacological Application in Treating Neurodegenerative
      Diseases: A Review.
AB  - BACKGROUND: Research on natural bioactive compounds has increased exponentially
      over the last decades. The discovery of new phytochemicals that possess
      pharmaceutical properties is useful in the development of therapeutic
      alternatives. The nerolidol (3,7,11-trimetil-1,6,10-dodecatrien-3-ol or 3,7,11
      trimetildodeca-1,6,10-trien-3-ol) has been extensively studied for its
      therapeutic potential because of its pharmacological activities in the treatment
      of neurodegenerative diseases. METHOD: All articles and patents regarding
      nerolidol and its pharmacological properties were revised, focusing mainly on the
      important properties in the treatment of neurodegenerative diseases. A thorough
      search in article databases (Science Direct, MEDLINE/PubMed, Scopus and Scielo)
      and patent database (WIPO, EPO, ESPTO, LATIPAT and INPI) was performed over the
      course of this study. RESULTS: Several studies stood out for their relevance
      regarding the treatment of neurodegenerative diseases. Nerolidol demonstrated
      anticholinesterasic, antioxidant, antinociceptive, anti-inflammatory and
      anxiolytic activities, thus classifying it as a promising phytochemical for the
      development of therapeutic drugs. CONCLUSION: Analysis suggested that nerolidol
      is a promising target for new drugs and treatment of neurodegenerative diseases.

PMID- 29210668
TI  - Identification and analysis of Eimeria nieschulzi gametocyte genes reveal
      splicing events of gam genes and conserved motifs in the wall-forming proteins
      within the genus Eimeria (Coccidia, Apicomplexa).
AB  - The genus Eimeria (Apicomplexa, Coccidia) provides a wide range of different
      species with different hosts to study common and variable features within the
      genus and its species. A common characteristic of all known Eimeria species is
      the oocyst, the infectious stage where its life cycle starts and ends. In our
      study, we utilized Eimeria nieschulzi as a model organism. This rat-specific
      parasite has complex oocyst morphology and can be transfected and even cultivated
      in vitro up to the oocyst stage. We wanted to elucidate how the known oocyst wall
      forming proteins are preserved in this rodent Eimeria species compared to other
      Eimeria. In newly obtained genomics data, we were able to identify different
      gametocyte genes that are orthologous to already known gam genes involved in the
      oocyst wall formation of avian Eimeria species. These genes appeared putatively
      as single exon genes, but cDNA analysis showed alternative splicing events in the
      transcripts. The analysis of the translated sequence revealed different conserved
      motifs but also dissimilar regions in GAM proteins, as well as polymorphic
      regions. The occurrence of an underrepresented gam56 gene version suggests the
      existence of a second distinct E. nieschulzi genotype within the E. nieschulzi
      Landers isolate that we maintain.

PMID- 29210670
TI  - Synthesis of non-toxic As and Cr nanoparticles through redox activity of highly
      flexible layered coordination polymer of Ni(II).
AB  - A simple method for the sequestration of As(III) and Cr(VI) from water has been
      demonstrated by utilizing a highly flexible porous coordination polymer (PCP) of
      Ni(II) in its as synthesized form or without solvent removal. This PCP reduces
      the high toxicity of As(III) and Cr(VI) ions into non-toxic As(0) and
      Cr/Cr2O3/CrO2 (zero, tri and tetravalent) nanoparticles (NPs) within its pores,
      and this is characterized by powder x-ray diffraction, x-ray photoelectron
      spectroscopy and high-resolution transmission electron microscopy analysis. The
      high functionality of this polymer is due to the presence of monodentate
      carboxylate groups of a benzenetricarboxylate linker, which provide anchoring
      sites to the metal ions of the metal precursors. Due to the highly oxidising
      nature of these toxic ions, a redox reaction takes place between the framework
      metal ions and toxic metal ions, which is explained by an electron paramagnetic
      resonance study. This is the first report to synthesize non-toxic, as well as
      useful, NPs of As and Cr from their highly toxic ions within the cavities of a
      PCP for remediation of the toxic waste stream and contaminated waste water.

PMID- 29210671
TI  - Laser-induced changes of nonlinear electronic transport properties in
      La<sub>0.75</sub>Ba<sub>0.25</sub>MnO<sub>3</sub> and
      (La<sub>0.6</sub>Pr<sub>0.4</sub>)<sub>0.67</sub>Ca<sub>0.33</sub>MnO<sub>3</sub>
AB  - We report photoinduced effects in the nonlinear third harmonic ac electric
      transport-which is a measure for the density of correlated polarons-in thin films
      of La<sub>0.75</sub>Ba<sub>0.25</sub>MnO<sub>3</sub> (LBMO) and
      (La<sub>0.6</sub>Pr<sub>0.4</sub>)<sub>0.67</sub>Ca<sub>0.33</sub>MnO<sub>3</sub>
      (LPCMO) manganites.&#13; Both materials show an enhancement of the third harmonic
      voltage in the vicinity of the metal-to-insulator transition, indicating strong
      electron-lattice correlations within a phase-separated state.&#13; Relatively low
      laser excitation with a pulse fluence of 11 MUJ/cm<sup>2</sup> leads to the
      increase (decrease) of the nonlinearity in LBMO (LPCMO).&#13; With a high pulse
      fluence of 8 mJ/cm<sup>2</sup> we were able to suppress the correlations also in
      LBMO, which is accompanied by a decrease of third harmonic voltage by 2.5 % in
      our time-averaging measurement technique.

PMID- 29210669
TI  - Extended low-resolution structure of a Leptospira antigen offers high
      bactericidal antibody accessibility amenable to vaccine design.
AB  - Pathogens rely on proteins embedded on their surface to perform tasks essential
      for host infection. These obligatory structures exposed to the host immune system
      provide important targets for rational vaccine design. Here, we use a
      systematically designed series of multi-domain constructs in combination with
      small angle X-ray scattering (SAXS) to determine the structure of the main
      immunoreactive region from a major antigen from Leptospira interrogans, LigB. An
      anti-LigB monoclonal antibody library exhibits cell binding and bactericidal
      activity with extensive domain coverage complementing the elongated architecture
      observed in the SAXS structure. Combining antigenic motifs in a single-domain
      chimeric immunoglobulin-like fold generated a vaccine that greatly enhances
      leptospiral protection over vaccination with single parent domains. Our study
      demonstrates how understanding an antigen's structure and antibody accessible
      surfaces can guide the design and engineering of improved recombinant antigen
      based vaccines.

PMID- 29210672
TI  - Interfacial engineering with ultrathin poly (9,9-di-n-octylfluorenyl-2,7-diyl)
      (PFO) layer for high efficient perovskite light-emitting diodes.
AB  - Organic-inorganic hybrid perovskites have attracted great attention in the field
      of lighting and display due to their very high color purity and low-cost solution
      process. Researchers have done a lot of work in realizing high performance
      electroluminescent devices. However, the current efficiency (CE) of methyl
      ammonium lead halide perovskite light-emitting diodes (PeLEDs) still needs to be
      improved. Herein, we demonstrate the enhanced performance of PeLEDs through
      introducing an ultrathin poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) buffer
      layer between poly(3,4-ethylendioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)
      and CH3NH3PbBr3 perovskite. Compared to the reference device without PFO, the
      optimal device luminous intensity, the maximum CE, and the maximum external
      quantum efficiency increases from 8139 cd m-2 to 30 150 cd m-2, from 7.20 cd A-1
      (at 6.8 V) to 10.05 cd A-1 (at 6.6 V), and from 1.73% to 2.44%, respectively. The
      ultrathin PFO layer not only reduces the exciton quenching at the interface
      between the hole-transport layer and emission layer, but also passivates the
      shallow-trap ensure increasing hole injection, as well as increases the coverage
      of perovskite film.

PMID- 29210673
TI  - Detecting beta-amyloid aggregation from time-resolved emission spectra.
AB  - The aggregation of beta-amyloids is one of the key processes responsible for the
      development of Alzheimer's disease. Early molecular-level detection of beta
      amyloid oligomers may help in early diagnosis and in the development of new
      intervention therapies. Our previous studies on the changes in beta-amyloid's
      single tyrosine intrinsic fluorescence response during aggregation demonstrated a
      four-exponential fluorescence intensity decay, and the ratio of the pre
      exponential factors indicated the extent of the aggregation in the early stages
      of the process before the beta-sheets were formed. Here we present a
      complementary approach based on the time-resolved emission spectra (TRES) of
      amyloid's tyrosine excited at 279 nm and fluorescence in the window 240-450 nm.
      TRES have been used to demonstrate sturctural changes occuring on the nanosecond
      time scale after excitation which has significant advantages over using steady
      state spectra. We demonstrate this by resolving the fluorescent species and
      revealing that beta-amyloid's monomers show very fast dielectric relaxation, and
      its oligomers display a substantial spectral shift due to dielectric relaxation,
      which gradually decreases when the oligomers become larger.

PMID- 29210674
TI  - Adsorption of phosphate ions from aqueous solutions by a CeO2 functionalized
      Fe3O4@SiO2 core-shell magnetic nanomaterial.
AB  - Phosphate is generally considered to be one of the nutrients for plants which may
      cause eutrophication of the aquatic environment. In this study, a CeO2
      functionalized Fe3O4@SiO2 core-shell magnetic nanomaterial (denoted as Fe3O4@SiO2
      CeO2) was prepared and used as the adsorbent to remove phosphate from water. The
      adsorbents were characterized by X-ray diffraction, transmission electron
      microscopy, X-ray photoelectron spectroscopy, and N2 adsorption/desorption
      isotherms. Characterization results show that the particle size is around 8.63
      nm, Brunauer-Emmett-Teller (BET) surface area is 179.7 m2 . g-1 and the pore
      volume is 0.39 cm3 . g-1 for magnetite Fe3O4@SiO2-CeO2. The adsorbents could be
      rapidly separated under an external magnetic field. Batch adsorption tests show
      that the Fe3O4@SiO2-CeO2 adsorbent exhibited high adsorption affinity for
      phosphate. Additionally, phosphate adsorption isotherms over the adsorbents could
      be well described by the Langmuir model, suggesting monolayer adsorption, and
      phosphate adsorption kinetics followed the pseudo-second-order kinetics.
      Moreover, increasing pH led to suppressed phosphate adsorption, and phosphate
      adsorption slightly increased with ionic strength.

PMID- 29210675
TI  - Hierarchical prediction of industrial water demand based on refined Laspeyres
      decomposition analysis.
AB  - A recent study decomposed the changes in industrial water use into three
      hierarchies (output, technology, and structure) using a refined Laspeyres
      decomposition model, and found monotonous and exclusive trends in the output and
      technology hierarchies. Based on that research, this study proposes a
      hierarchical prediction approach to forecast future industrial water demand.
      Three water demand scenarios (high, medium, and low) were then established based
      on potential future industrial structural adjustments, and used to predict water
      demand for the structural hierarchy. The predictive results of this approach were
      compared with results from a grey prediction model (GPM (1, 1)). The comparison
      shows that the results of the two approaches were basically identical, differing
      by less than 10%. Taking Tianjin, China, as a case, and using data from 2003
      2012, this study predicts that industrial water demand will continuously
      increase, reaching 580 million m3, 776.4 million m3, and approximately 1.09
      billion m3 by the years 2015, 2020 and 2025 respectively. It is concluded that
      Tianjin will soon face another water crisis if no immediate measures are taken.
      This study recommends that Tianjin adjust its industrial structure with water
      savings as the main objective, and actively seek new sources of water to increase
      its supply.

PMID- 29210676
TI  - Enrichment and application of nitrifying activated sludge in membrane
      bioreactors.
AB  - In this study, nitrifying bacteria were enriched in a membrane bioreactor (MBR,
      R1) and their bioaugmentation effectiveness was evaluated in another two MBRs (R2
      and R3). Nitrifying activated sludge (NAS) with high nitrification activity of up
      to 3,000 mg-N/(L.d)-1 was successfully enriched in R1. The results showed that
      chemical oxygen demand concentration of 100-200 mg/L had no negative effect on
      NAS enrichment but reduced the ratio of bacterial nitrifiers. Moreover, the cell
      concentration of nitrifying bacteria in NAS, which was 3.1 * 1011 cells/L, was
      similar to that of the commercial bacterium agent. For the bioaugmentation test,
      the reactor inoculated with 14% NAS achieved a 23% higher NH4+-N removal
      efficiency than that of the uninoculated reactor. Along with the improvement of
      nitrification performance, the bacterial nitrifiers abundance and microbial
      richness remarkably increased after bioaugmentation. These results suggested that
      the MBR system could efficiently enrich nitrifying bacteria using organic carbon
      containing culture medium, and potentially act as a side-stream reactor to
      enhance the nitrification function of the wastewater treatment plant.

PMID- 29210677
TI  - Simultaneous removal of nitrogen and phosphorus by cetylpyridinium bromide
      modified zeolite.
AB  - In this study, surfactant modified zeolite-clinoptilolite (SMZ) by CPB
      (cetylpyridinium bromide) was used for simultaneous removal of ammonium, nitrate
      and phosphate in synthetic wastewater, and the sorption properties of SMZ were
      determined and compared with natural zeolite. Results showed that natural
      clinoptilolite had good affinity for ammonium (8.940 mg/g), but not for nitrate
      (0.427 mg/g) and phosphate (0.801 mg/g). With the increase of surfactant loading
      from 5 g/L to 40 g/L, the sorption capacity for nitrate increased from 0.462 mg/g
      to 4.661 mg/g. when the surfactant loading is 40 g/L, the SMZ has a phosphate
      adsorption capacity of 2.119 mg/g. The SMZ had a significant enhancement on
      nitrate and phosphate sorption, could simultaneously remove ammonium, nitrate and
      phosphate at specific conditions, with removal efficiency up to 85.2%, 83.1% and
      56.7%, respectively. Orthogonal experiments showed that ammonium concentration
      was the most important factor for ammonium sorption on SMZ. Surfactant loading
      was the major factor for nitrate and phosphate sorption. With the increase of
      surfactant loading from 5 g/L to 40 g/L, the sorption capacity for nitrate
      increased from 0.462 mg/g to 4.661 mg/g. When the surfactant loading is 40 g/L,
      the SMZ has the best phosphate adsorption capacity 2.119 mg/g. Samples were
      characterized by X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET). Semi
      empirical quantum mechanics molecular simulation indicated that electrostatic
      attraction existed between CPB and dihydrogen phosphate ion. Results indicate
      that SMZs might have great potential of removing cations and anions
      simultaneously in the aquatic environment, which is good for eutrophication
      control and nutrients removal.

PMID- 29210678
TI  - Optimizing electrocoagulation process using experimental design for COD removal
      from unsanitary landfill leachate.
AB  - Leachate is the most difficult wastewater to be treated due to its complex
      content and high pollution release. For this reason, since it is not possible to
      be treated with a single process, a pre-treatment is needed. In the present
      study, a batch electrocoagulation reactor containing aluminum and iron electrodes
      was used to reduce chemical oxygen demand (COD) from landfill leachate (Tunceli,
      Turkey). Optimization of COD elimination was carried out with response surface
      methodology to describe the interaction effect of four main process independent
      parameters (current density, inter-electrode distance, pH and time of
      electrolysis). The optimum current density, inter-electrode distance, pH and time
      of electrolysis for maximum COD removal (43%) were found to be 19.42 mA/m2, 0.96
      cm, 7.23 and 67.64 min, respectively. The results shown that the
      electrocoagulation process can be used as a pre-treatment step for leachate.

PMID- 29210679
TI  - Assessment on inflow and infiltration in sewerage systems of Kuantan, Pahang.
AB  - Inflow and infiltration are important aspects of sewerage systems that need to be
      considered during the design stage and constantly monitored once the sewerage
      system is in operation. The aim of this research is to analyse the relationship
      of rainfall as well as inflow infiltration with sewage flow patterns through data
      collected from fieldwork. Three sewer pipelines were selected at the residential
      areas of Taman Lepar Hilir Saujana, Bandar Putra and Kota Sas for data
      collection. Sewage flow data were collected in terms of flowrate, velocity and
      depth of flow using flowmeters with ultrasonic sensors that utilize the
      continuous Doppler effect in the sewer pipelines, while rainfall intensity data
      were collected using rain gauges installed at the study locations. Based on the
      result, the average infiltration rates of Qpeak and Qave for the locations were
      17% and 21%, which exceeded the respective values of 5% and 10% stated in Hammer
      and Hammer. The flowrate of wastewater in the sewer pipelines was found to be
      directly proportional to rainfall. These findings indicate that the sewer
      pipelines in the study areas may have been affected by capacity reduction,
      whereas the sewerage treatment plants receiving the wastewater influent may have
      been overloaded.

PMID- 29210680
TI  - Starch degradation and intermediate dynamics in flocculated and dispersed
      microcosms.
AB  - A large fraction of the organic substrate in municipal wastewater is particulate.
      Prior to uptake, particles have to be degraded through potentially a range of
      intermediates. However, research on intermediate dynamics during particle
      hydrolysis is limited. In this paper, batch experiments on flocculated and
      dispersed biomass microcosms using starch as particulate substrate are reported.
      Overall hydrolysis rate was not significantly different between the two systems.
      Particle colonization, and increased particle porosity in combination with
      particle breakup, led to increased substrate availability over time. Particle
      breakup was more important for flocculated biomass, while increased particle
      porosity and particle colonization played a larger role for dispersed biomass.
      During particle degradation intermediates were formed; however, all intermediate
      polymer sizes were not formed to the same extent. This can be explained by non
      random enzymatic degradation, where some products are preferred over others.
      Intermediates' dynamics also depend on the biomass structure, and in a floc-based
      system, diffusion limitations allow glucose to accumulate in the system.

PMID- 29210681
TI  - Evaluating membrane performance in recycled water treatment plants for assets
      replacement strategy.
AB  - Membranes are an important barrier used in recycled water treatment plants for
      pathogen removal. Understanding performance over operational life is important to
      inform membrane replacement. In this study, full scale virus challenge testing
      was conducted on newly commissioned membranes to validate virus log removal
      values for accreditation. After six years of operation, the membrane integrity
      was repeated to ensure compliance with the state regulatory health authority and
      gain an understanding of the asset's condition. Membrane performance was assessed
      using a combination of complementary tests including membrane autopsy and
      chemical tolerance testing to assess individual modules and selected membrane
      fibres, followed by a full scale virus challenge for whole of unit assessment.
      The results demonstrated that the aged membrane fibres were intact and had not
      been affected by long-term exposure to chlorine, which provides valuable
      information for membrane asset replacement strategies.

PMID- 29210682
TI  - Advanced treatment of landfill leachate membrane concentrates: performance
      comparison, biosafety and toxic residue analysis.
AB  - With the improvement of people's consciousness about health, more attention has
      been paid to the biosafety of effluent reaching conventional discharge standard.
      In this contribution, removal efficiency of chemical oxygen demand (COD), acute
      toxicity, genotoxicity and estrogenicity in landfill leachate membrane
      concentrates (MCs) among UV-Fenton, Fenton and activated carbon adsorption
      process were compared. Daphnia magna acute toxicity assay, comet assay,
      cytokinesis-block micronucleus and E-screen assay were performed to assess
      whether the effluent reaching the main parameters of Chinese Discharge Standard
      (GB 16889-2008) still had toxic residues. Under the conditions that COD of
      effluents treated by the three processes were up to the discharge standard, no
      obvious toxic residue was found in the effluent of UV-Fenton treatment, but
      effluent from Fenton or activated carbon adsorption process showed genotoxicity
      or estrogenicity to some extent. Dynamic analysis of UV-Fenton degradation
      process for estrogen simulation solutions was also conducted, and the formation
      of intermediates was detected by gas chromatography-mass spectrometry (GC/MS).
      Toxic residues might be caused by the lack of treatment duration and the
      formation of more toxic intermediates. UV-Fenton was found to be efficient for
      the treatment of MCs. Biosafety should be concerned when a new wastewater
      discharge standard is being established.

PMID- 29210683
TI  - Improving the selectivity of magnetic graphene oxide through amino modification.
AB  - Fabricating efficient materials for environmental purposes is a priority and the
      subject of much attention nowadays. The objectives of this study are to adopt an
      amino modification approach to improve the selective removal capacity of magnetic
      graphene oxide (MGO) for Cu(II) ions, and explore how it performs in single and
      binary systems by taking Cd(II) as a comparison. After grafting the amino groups,
      the final material exhibited promoted capacities for Cu(II) and Cd(II), and a
      more apparent selective adsorption process can be observed. The maximum
      equilibrium adsorbances of amino modified MGO were 578.1 mg g-1 for Cu(II) and
      184.7 mg g-1 for Cd(II) under our experimental conditions, compared with 319.1 mg
      g-1 and 161.2 mg g-1 of MGO for Cu(II) and Cd(II), respectively. Characterization
      results and experiment data confirmed that the introduction of N species
      contributed to the enhancement. This may pave the way for better understanding of
      the underlying mechanism, and provide inspiration for synthesizing new
      adsorbents.

PMID- 29210684
TI  - Control systems for olive mill wastewater treatment with ultrafiltration and
      nanofiltration membrane in series based on the boundary flux theory.
AB  - Proper membrane process design can be a difficult task to accomplish when fouling
      is present, and must be faced. Engineers usually consider the project variables
      concerning productivity and selectivity and follow these targets. However, in the
      presence of fouling, additional parameters must be considered, implying better
      knowledge of fouling phenomena. One possible solution to increase the reliability
      of a process is the use of stable control systems. This article reports a
      suitable method to reach this target, based on the boundary flux theory. The
      knowledge of the boundary flux values permits avoidance of high fouling operating
      conditions on a selected membrane. The goal here was to determine the framework
      for control of an ultrafiltration (UF) and nanofiltration (NF) batch membranes-in
      series process treatment for olive mill wastewater, relying on these boundary
      flux points, which will thereafter serve for the automatic control of the process
      by an advanced control system. In this work, boundary flux values equal to 10 L h
      1 m-2 for the UF membrane module and 14.3 L h-1 m-2 for the NF one were
      estimated. Moreover, the membrane constant permeability loss, measured by
      integrating the sub-boundary fouling index, was estimated to be reduced in the
      order of 65.4% for the NF membrane after the applied pretreatment and UF. This
      strategy permitted attaining stable and constant productivity for both membranes.
      Moreover, it is shown that, relying on the boundary flux modelization, both types
      of control systems (feed control and pressure control) could be used reliably.
      The proposed approach could help safely narrow the overdesign of membrane
      processes due to fouling issues and thus would have an impact on the reduction of
      the costs for both membrane processes.

PMID- 29210686
TI  - A modelling study of the event-based retention performance of green roof under
      the hot-humid tropical climate in Kuching.
AB  - The influences of climate on the retention capability of green roof have been
      widely discussed in existing literature. However, knowledge on how the retention
      capability of green roof is affected by the tropical climate is limited. This
      paper highlights the retention performance of the green roof situated in Kuching
      under hot-humid tropical climatic conditions. Using the green roof water balance
      modelling approach, this study simulated the hourly runoff generated from a
      virtual green roof from November 2012 to October 2013 based on past
      meteorological data. The result showed that the overall retention performance was
      satisfactory with a mean retention rate of 72.5% from 380 analysed rainfall
      events but reduced to 12.0% only for the events that potentially trigger the
      occurrence of flash flood. By performing the Spearman rank's correlation
      analysis, it was found that the rainfall depth and mean rainfall intensity,
      individually, had a strong negative correlation with event retention rate,
      suggesting that the retention rate increases with decreased rainfall depth. The
      expected direct relationship between retention rate and antecedent dry weather
      period was found to be event size dependent.

PMID- 29210685
TI  - Continuous treatment of Acid Red B with activated sludge bioaugmented by a yeast
      Candida tropicalis TL-F1 and microbial community dynamics.
AB  - Continuous treatment of Acid Red B (ARB) with activated sludge (AS) bioaugmented
      by an azo-degrading yeast Candida tropicalis TL-F1 under aerobic conditions was
      investigated in the form of sequencing batch tests. Dynamics of both bacterial
      and fungal communities were analyzed using polymerase chain reaction followed by
      denaturing gradient gel electrophoresis (PCR-DGGE) method. The results showed
      that bioaugmentation with the yeast TL-F1 improved the performance of AS for
      continuously decolorizing, degrading and detoxifying ARB. Meanwhile, the AS
      systems bioaugmented by the yeast TL-F1 showed higher sludge concentration and
      better AS settleability. The result of PCR-DGGE suggested that microbial
      communities of both bacteria and fungi shifted due to treatment of ARB and
      bioaugmentation. Some dominant bacteria and fungi were identified as probably
      efficient degraders of ARB or its decolorization byproducts. Furthermore, the
      yeast TL-F1 was found as one of the dominant fungi in all the three bioaugmented
      systems, suggesting that bioaugmentation was successful due to the colonization
      of the yeast TL-F1 in AS systems.

PMID- 29210687
TI  - Identification and risk assessment of human and veterinary antibiotics in the
      wastewater treatment plants and the adjacent sea in Tunisia.
AB  - In the following study, we came up with and validated a prompt, sensitive and
      precise method for the simultaneous determination of 56 antimicrobial drugs
      (tetracyclines, sulfonamides, beta-lactams, macrolides and quinolones) using the
      ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
      This method was implemented with success to determine antibiotics in samples
      collected from four wastewater treatment plants and five coasts in Tunisia.
      Results showed the presence of high concentrations of antibiotics that ranged
      from 0.1 to 646 ng mL-1, which can induce many negative impacts on health and the
      environment. For this reason, we have opted to evaluate toxicity of wastewater
      samples using a battery of biotests. In fact, genotoxicity was assessed using
      three tests: Vitotox, comet and micronucleus assays. The input and output of
      wastewater treatment plants induced a strongly genotoxic effect on the Salmonella
      typhimurium TA104 prokaryotic Vitotox assay. This result was confirmed using the
      comet and the micronucleus assays performed on the human liver hepatocellular
      carcinoma cells. The genotoxic power of the tested wastewater treatment plants'
      samples could be attributed to the presence of the higher quantities of
      antibiotics that are detected in these samples and to the antibiotic and organic
      compound cocktails.

PMID- 29210688
TI  - The importance of surface functional groups in the adsorption of copper onto
      walnut shell derived activated carbon.
AB  - In this study, activated carbon (AC) was prepared from walnut shell using
      chemical activation. The surface chemistry of the prepared AC was modified by
      introducing or blocking certain functional groups, and the role of the different
      functional groups involved in the copper uptake was investigated. The structural
      and chemical heterogeneity of the produced carbons are characterized by Fourier
      transform infrared spectrometry, X-ray photoelectron spectroscopy, Boehm
      titration method and N2/77 K adsorption isotherm analysis. The equilibrium and
      the kinetics of copper adsorption onto AC were studied. The results demonstrated
      that the functional groups on AC played an important role in copper uptake. Among
      various surface functional groups, the oxygen-containing group was found to play
      a critical role in the copper uptake, and oxidation is the most effective way to
      improve Cu (II) adsorption onto AC. Ion-exchange was identified to be the
      dominant mechanism in the copper uptake by AC. Some other types of interactions,
      like complexation, were also proven to be involved in the adsorption process,
      while physical force was found to play a small role in the copper uptake. The
      regeneration of copper-loaded AC and the recovery of copper were also studied to
      evaluate the reusability of the oxidized AC.

PMID- 29210689
TI  - An evaluation of hydrologic modeling performance of EPA SWMM for bioretention.
AB  - Recent techniques should be investigated in detail to avoid present and future
      problems of urbanization like flood, drought and water pollution. Low Impact
      Development (LID) Best Management Practices (BMPs) such as bioretentions, green
      roofs, rain barrels, vegetative swales, and permeable pavements have been
      implemented to diminish the adverse effects of urbanization. In this study, a
      hydrological model for a Rainfall-Watershed-Bioretention (RWB) system is
      developed by using the Environmental Protection Agency Storm Water Management
      Model (EPA SWMM). RWB system is an experimental setup which consists of an
      artificial rainfall system, a drainage area and four bioretention columns with
      different soil mixtures. The hydrological modeling capability of SWMM for
      bioretentions is presented using the experimental data obtained from the
      experiments conducted in the RWB system under different rainfall events and for
      bioretentions with different designs. Finally, the modeling results of SWMM are
      compared with the results of the Hydrological Model of RWB (HM-RWB) system.
      Results show that EPA SWMM performs well in modeling bioretentions whereas the
      results of HM-RWB are in better agreement with the experimental data.

PMID- 29210690
TI  - Numerical modelling of a three-phase internal air-lift circulating photocatalytic
      reactor.
AB  - The photocatalytic degradation process has been recognized as a low-cost,
      environmentally friendly and sustainable technology for water and wastewater
      treatment. As a key carrier of the photocatalytic process, the semiconductor TiO2
      has been used in many studies. Analysis and modelling of hydrodynamics in the
      three-phase flow system can provide useful information for process design,
      operation and optimization of the three-phase flow photocatalytic reactor, which
      requires research on the mixing and flow characteristics of the interphase
      regions in the reactor. In this study, we modelled the hydrodynamics in an
      internal air-lift circulating photocatalytic reactor using an Eulerian multi
      fluid approach. Localized information on phase holdup, fluid flow patterns and
      mixing characteristics was obtained. The simulation results revealed that the
      distribution of solid particle concentration depends on the flow field in the
      internal air-lift circulating photocatalytic reactor. The distance between the
      draft tube and wall of the reactor and changes in the superficial gas velocity
      (Ug) were found to be influential factors in reactor performance. The
      computational model developed could support optimizing reactor design to improve
      the hydrodynamics and provide guidance for scale-up.

PMID- 29210691
TI  - Removing 2,4-dichlorophenol from aqueous environments by heterogeneous catalytic
      ozonation using synthesized MgO nanoparticles.
AB  - 2,4-Dichlorophenol (2,4-DCP) is one of the seriously toxic chlorophenol compounds
      found in agricultural environments, in water disinfected by chlorine, and in
      outgoing effluents from the pulp and paper industries and paper manufacturing
      factories. This research studied the feasibility of using MgO nanoparticles (MgO
      NPs) as a catalyst in the ozonation process for removing 2,4-DCP from aqueous
      environments under laboratory conditions. This study was conducted using a
      laboratory-scale semi-continuous reactor. It studied the effects of critical
      variables such as solution pH, ozonation time, dose of MgO-NPs and initial 2,4
      DCP concentration. A statistical model of response surface model (RSM) was
      designed and utilized to obtain the optimum experimental conditions. Analysis of
      the data showed that initial concentration of 2,4-DCP and dose of MgO-NPs had the
      maximum effect on the response variable (percentage degradation of 2,4-DCP).
      Moreover, based on analysis of variance on the model, the optimum removal
      conditions were reaction time of 50 min, pH > 7, initial 2,4-DCP concentration of
      less than 50 mg/L, and an MgO-NPs dose of 0.3 mg/L. Under these optimum
      conditions, a removal efficiency of 99.99% was achieved. In addition, results
      indicated that catalytic ozonation in the presence of MgO-NPs was very efficient
      at removing 2,4-DCP from aqueous environments.

PMID- 29210692
TI  - Preparation and catalytic performance of copper-containing magnetic catalysts for
      degradation of azo dye (direct violet).
AB  - A novel magnetically separable magnetic activated carbon supporting-copper (MCAC)
      catalyst for catalytic wet peroxide oxidation (CWPO) was prepared by chemical
      impregnation. The prepared samples were characterized by X-ray diffraction (XRD),
      Brunauer-Emmett-Teller (BET) method, and scanning electron microscopy (SEM)
      equipped with energy dispersive spectrometry (EDS). The catalytic performance of
      the catalysts was evaluated by direct violet (D-BL) degradation in CWPO
      experiments. The influence of preparative and operational parameters (dipping
      conditions, calcination temperature, catalyst loading H2O2 dosage, pH, reaction
      temperature, additive salt ions and initial D-BL concentration) on degradation
      performance of CWPO process was investigated. The resulting MCAC catalyst showed
      higher reusability in direct violet oxidation than the magnetic activated carbon
      (MAC). Besides, dynamic tests also showed the maximal degradation rate reached
      90.16% and its general decoloring ability of MCAC was 34 mg g-1 for aqueous D-BL.

PMID- 29210693
TI  - Impact on nitrifiers of full-scale bioaugmentation.
AB  - Nitrifiers are the slowest growing bacteria used in conventional biological
      wastewater treatment. Furthermore, their growth rate is seriously hampered by low
      temperature. As a result, the volume needed for nitrification dominates the
      volume of the biological reactors at a wastewater treatment plant. As a way of
      enhancing nitrification and reducing this volume, bioaugmentation can be used.
      Nitrifiers from a side-stream plant can be inoculated to the mainstream process,
      which is thereby boosted. The effect of bioaugmentation can be measured in
      different ways. This full-scale study focuses on the effect of bioaugmentation
      from a microbial point of view by using 16S rRNA amplicon sequencing. The study
      reveals how bioaugmentation increases the diversity of nitrifiers in the
      mainstream process and in the side-stream plant; that the abundance of nitrifiers
      is increased in the mainstream process; the interaction between nitrifiers from
      the side-stream plant and mainstream process; and the effect of bioaugmentation
      on nitrifying genera and species over time. To our knowledge, this detailed
      microbial information on nitrifying species during a full-scale bioaugmentation
      study has not been presented before.

PMID- 29210694
TI  - Effect of phosphorus on nitrogen migration and transformation in deep subsurface
      wastewater infiltration systems.
AB  - This paper investigates the effect of phosphorus on nitrogen migration and
      transformation during the sewage purification processes in deep subsurface
      wastewater infiltration systems. Good performance was achieved with a hydraulic
      loading rate of 0.1 m3/m2.d, indicating that the effluent water quality could
      meet the primary grade A values as put forth by the 'Cities Sewage Treatment
      Plant Pollutant Discharge Standard' (GB18918-2002). In addition, the results of
      three inflow total phosphorus (TP) concentrations (5 mg L-1, 15 mg L-1, and 30 mg
      L-1) indicated that high-levels of phosphorus were more advantageous in regards
      to improving the activity of denitrifying bacteria in soil and strengthening the
      effect of nitrogen removal, suggesting that the effluent total nitrogen (TN)
      concentration could meet the primary grade A standard (TN <= 15 mg L-1). It was
      further observed that soil depth was less crucial when inflow TP concentrations
      were higher. Therefore, the results indicated that inflow phosphorus
      concentrations could greatly influence nitrogen migration and transformation in
      deep subsurface wastewater infiltration systems.

PMID- 29210695
TI  - Biodegradation of dairy wastewater using bacterial and fungal local isolates.
AB  - Dairy wastewater contains high levels of organics and other pollutants. The
      present study was carried out to investigate the biodegradation process of dairy
      effluents using some locally isolated bacteria and fungi. Four different dairy
      effluent samples were collected from Obour and 6th October industrial cities,
      Egypt. Five bacterial species (Pseudomonas aeruginosa, Bacillus subtilis,
      Lactobacillus delbrueckii, Staphylococcus aureus and Enterococcus hirae) and
      three fungal strains (Alternaria sp., Fusarium sp. and Aspergillus sp.) were
      isolated from dairy wastewater samples, identified and used for biodegradation
      process. Bacterial and fungal consortia were prepared separately in the
      laboratory. Two-stages (aeration and filtration) laboratory scale model was
      designed. Rice straw and activated carbon layers were used as filtration media.
      Results indicated the great ability of both studied bacteria and fungi for
      removal of organics (biological oxygen demand removal percent were 78.7% and
      74.7% for bacteria and fungi, respectively) and the improvement of the
      physicochemical quality (total suspended solids removal percent were 99.3% and
      99.0% for bacteria and fungi, respectively) of the dairy effluent. The addition
      of rice straw and activated carbon increased removal efficiencies. Biodegradation
      of dairy wastewater depending on local microorganisms is an effective, cheap and
      eco-friendly technology.

PMID- 29210696
TI  - Effects of the chemical characteristics and concentration of inorganic suspended
      solids on nitrification in freshwater.
AB  - The effect of inorganic suspended solids (ISS) on nitrification in freshwater
      samples has been described inconsistently and remains unclear. This study
      therefore investigated the effects of the chemical characteristics and
      concentration of ISS on the nitrification rate by focusing on Nitrosomonas
      europaea and Nitrobacter winogradskyi as the two most dominant nitrification
      species in freshwater. Batch-wise experiments were conducted using three
      chemically well-characterized ISS (i.e. the clay minerals montmorillonite,
      sericite, and kaolinite in the concentration range 0-1,000 mg L-1). The results
      show that the ammonium oxidation rate constant (kNH4) was significantly affected
      by the ISS type, whereas changes in the ISS concentration had an insignificant
      effect on kNH4, except for kaolinite. The highest kNH4 was observed in samples
      containing sericite (kNH4, 0.067 L mg-1 day-1), followed by samples containing
      montmorillonite (kNH4, 0.044 L mg-1 day-1). The ammonium oxidation rate was low
      in the control and kaolinite samples. Nitrite oxidation was enhanced in the
      presence of all types of ISS. The rate constants of ISS-mediated nitrite
      oxidation (kNO2, 0.13-0.21 L mg-1 day-1) were not significantly different among
      the three types of ISS, but kNO2 was significantly affected by ISS concentration.
      Overall, our study indicated various effects of the ISS type and concentration on
      nitrification and, in particular, a notable positive effect of sericite.

PMID- 29210697
TI  - The adsorption and Fenton behavior of iron rich Terra Rosa soil for removal of
      aqueous anthraquinone dye solutions: kinetic and thermodynamic studies.
AB  - Adsorption and advanced oxidation processes are being extensively used for
      treatment of wastewater containing dye chemicals. In this study, the adsorption
      and Fenton behavior of iron rich Terra Rosa soil was investigated for the
      treatment of aqueous anthraquinone dye (Reactive Blue 19 (RB19)) solutions. The
      impact of pH, initial dye concentration, soil loading rate, contact time and
      temperature was systematically investigated for adsorption process. A maximum
      removal efficiency of dye (86.6%) was obtained at pH 2, soil loading of 10 g/L,
      initial dye concentration of 25 mg/L, and contact time of 120 min. Pseudo-first
      order, pseudo-second-order, Elovich, and Weber-Morris kinetic models were applied
      to describe the adsorption mechanism and sorption kinetic followed a pseudo
      second-order kinetic model. Moreover, Langmuir, Freundlich and Temkin isotherm
      models were used to investigate the isothermal mechanism and equilibrium data
      were well represented by the Langmuir equation. The maximum adsorption capacity
      of soil was found as 4.11 mg/g using Langmuir adsorption isotherm. The effect of
      soil loading and hydrogen peroxide (H2O2) dosage was solely tested for Fenton
      oxidation process. The highest removal efficiency of dye (89.4%) was obtained at
      pH 2, H2O2 dosage of 10 mM, soil loading of 5 g/L, initial dye concentration of
      50 mg/L, and contact time of 60 min. Thermodynamic studies showed that when the
      adsorption dosage of dye was 25 mg/L at 293-313 K, adsorption enthalpy (DeltaH)
      and entropy (DeltaS) were negative and adsorption free energy (DeltaG) was
      positive. This result indicated that the adsorption was exothermic. Morphological
      characteristics of the soil were evaluated by X-ray fluorescence (XRF), scanning
      electron microscopy (SEM), and attenuated total reflection Fourier transform
      infrared (ATR-FTIR) spectroscopy before and after the adsorption and oxidation
      process.

PMID- 29210698
TI  - Methylene blue removal by carbonized textile sludge-based adsorbent.
AB  - Colored effluent and a large amount of sludge are major pollutant sources derived
      from textile industry activity. In this research, the idea for converting textile
      sludge into a potential adsorbent was conducted through a carbonization process
      in order to solve the colored effluent problem. Textile sludge was carbonized at
      a temperature ranging from 400 to 800  degrees C in the absence of oxygen.
      Maximum adsorption capacity of carbonized sludge for methylene blue removal
      reached 60.30 mg/g when the sludge was carbonized at 600  degrees C with specific
      surface area of 138.9 m2/g and no significant alteration was observed until 800 
      degrees C. Experimental research by using a real wastewater also showed that
      there was almost no disruption during adsorption of methylene blue into surface
      of carbonized sludge. While reactivation process revealed that the regeneration
      of carbonized sludge was applicable by secondary heating at the same
      carbonization temperature. Furthermore, the application of this research
      demonstrated that the carbonized textile sludge was a good adsorbent for
      methylene blue removal and had a capability to be reactivated.

PMID- 29210699
TI  - Scaling of nanofiltration membranes used for chromium(III) ions recovery from
      salt solutions.
AB  - The effect of membranes' structure on the efficiency of chromium(III) ions
      recovery from salt solution at low pH and the efficiency of chemical cleaning of
      these membranes were analyzed in this work. The nanofiltration membranes (DL and
      HL) used in this study were provided by GE Osmonics. The DL membrane had an
      irregular, dense support layer structure, while the HL membrane had a loose one.
      In the case of the DL membrane, it was found that, under tested solutions, the
      layer of mineral scale formed on the surface gradually decreases the membrane
      permeability coefficient. In the case of the DL membrane, the scaling was
      observed only on the surface. On the other hand, a small roughness (118A) and low
      density charge (zeta potential at level -4) of the HL membrane causes an uneven
      growth in deposits and, consequently, irregular nature of the surface structure
      which hinders the removal of accumulated sediment from the tested membranes'
      surface. Additionally, the loose structure of the support layer of HL membrane
      contributes to its internal scaling. Consequently, the permanently loose
      structure of the HL membrane permeability coefficient was observed.

PMID- 29210700
TI  - Characterization of a supported ionic liquid membrane used for the removal of
      cyanide from wastewater.
AB  - This work evaluated the performance of ionic liquids (ILs) in supported liquid
      membranes in the removal of total cyanide from wastewater. Membranes were
      characterized by scanning electron microscopy and contact angle measurements to
      study the membrane morphology and wetting ability. In particular, the effects of
      operational parameters such as membrane immersion time, feed-phase concentration,
      and pH on cyanide removal were investigated. ILs are organic salts that are
      entirely composed of organic cations and either organic or inorganic anions.
      Since their vapor pressure is negligible, they can be handled easily; this
      characteristic gives rise to their 'green' nature. In this study, a hydrophobic
      IL, 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6), was immobilized
      in the pores of a solid polymeric support made of polyvinylidene fluoride. The
      optimal conditions were as follows: 1 hour membrane immersion time, 312.24 mg/L
      feed-phase concentration, a feed-phase pH of 4, 3% NaOH solution, and 1 hour
      stirring time. The cyanide removal was 95.31%. The treatment of cyanide using
      supported ionic liquid membrane (SILM) technology is a method with potential
      applications in industry.

PMID- 29210701
TI  - Bioelectrochemical nitrogen removal as a polishing mechanism for domestic
      wastewater treated effluents.
AB  - Addition of an external carbon source is usually necessary to guarantee a
      sufficiently high C/N ratio and enable denitrification in wastewater treatment
      plants (WWTPs). Alternatively, denitrification processes using autotrophic
      microorganisms have been proposed i.e., with the use of H2 as electron donor or
      with the use of cathodic denitrification in bioelectrochemical systems (BES), in
      which electrons are transferred directly to a denitrifying biofilm. The aim of
      this work was to investigate and demonstrate the feasibility of applying an easy
      to-operate BES as a polishing mechanism for treated secondary clarified effluent
      from a municipal WWTP, containing low levels of organic matter, buffer capacity
      and low concentrations of remaining nitrate. In the proposed system, nitrogen
      removal rates (0.018-0.121 Kg N m-3 d-1) increased with the nitrogen loading
      rates, suggesting that biofilm kinetics were not rate limiting. The lowest energy
      consumption for denitrification was 12.7 kWh Kg N-1, equivalent to 0.021 kWh m-3
      and could be further reduced by 14% by adding recirculation circuits within both
      the anode and cathode.

PMID- 29210702
TI  - Effects of tannic acid on membrane fouling and membrane cleaning in forward
      osmosis.
AB  - The fouling behavior during forward osmosis (FO) was investigated. Tannic acid
      was used as a model organic foulant for natural organic matter analysis since the
      main characteristics are similar, and calcium ions were added at different
      concentrations to explore the anti-pollution capability of FO membranes. The
      initial permeate flux and calcium ions strength were varied in different
      operating conditions to describe membrane fouling with membrane cleaning methods.
      The observed flux decline in FO changed dramatically with the type of foulant and
      the type of draw solution used to provide the osmotic driving force. Calcium ions
      aggravated membrane fouling and decreased transmembrane flux. Membrane cleaning
      methods included physical and physicochemical approaches, and there was no
      obvious difference among the typical cleaning methods (i.e., membrane flushing
      with different types of cleaning fluids at various crossflow velocities and
      backwashing with varying osmotic driving forces) with respect to flux recovery.
      Ultrasonic cleaning damaged the membrane structure and decreased permeate flux,
      and reverse diffusion of salt from the draw solution to the feed side accelerated
      after cleaning.

PMID- 29210704
TI  - Effect of Stretching Combined With Ultrashort Wave Diathermy on Joint Function
      and Its Possible Mechanism in a Rabbit Knee Contracture Model.
AB  - OBJECTIVE: The aim of this study was to investigate the therapeutic effect of
      stretching combined with ultrashort wave on joint contracture and explore its
      possible mechanism. DESIGN: Thirty-two rabbits underwent unilateral
      immobilization of a knee joint at full extension to cause joint contracture. At 6
      wks after immobilization, the rabbits were randomly divided into the following
      four groups: natural recovery group, stretching treatment group, ultrashort wave
      treatment group, and combined treatment group. For comparison, eight control
      group animals of corresponding age were also examined. The effect of stretching
      and ultrashort wave treatment on joint contracture was assessed by measuring the
      joint range of motion, evaluating the collagen deposition of joint capsule and
      assessing the mRNA and protein levels for transforming growth factor beta1 in the
      joint capsule. RESULTS: The combined treatment group led to the best recovery of
      joint function. The combined treatment with stretching and ultrashort wave was
      more effective than stretching or ultrashort wave treatment alone against the
      synovial thickening of suprapatellar joint capsule, the collagen deposition of
      anterior joint capsule, and the elevated expression of transforming growth factor
      beta1 in the joint capsule. CONCLUSIONS: Stretching combined with ultrashort wave
      treatment was effective in improving joint range of motion, reducing the
      biomechanical, histological, and molecular manifestations of joint capsule
      fibrosis in a rabbit model of extending joint contracture.

PMID- 29210703
TI  - High-rate nitrification of electronic industry wastewater by using nitrifying
      granules.
AB  - Nitrifying granules have a high sedimentation property and an ability to maintain
      a large amount of nitrifying bacteria in a reaction tank. Our group has examined
      the formation process of nitrifying granules and achieved high-rate nitrification
      for an inorganic synthetic wastewater using these granules. In this research, a
      pilot-scale test plant with an 850-liter reaction tank was assembled in a
      semiconductor manufacturing factory in order to conduct a continuous water
      conduction test using real electronics industry wastewater. The aim was to
      observe the formation of nitrifying granules and determine the maximum ammonia
      removal rate. The average granule diameter formed during the experiment was 780
      MUm and the maximum ammonia removal rate was observed to be 1.5 kgN.m-3.day-1 at
      20  degrees C, which is 2.5-5 times faster than traditional activated sludge
      methods. A fluorescence in situ hybridization analysis showed that beta
      proteobacterial ammonia oxidizing bacteria and the Nitrospira-like nitrite
      oxidizing bacteria dominate the bacteria population in the granules, and their
      strong aggregation capacity might confer some benefits to the formation of these
      nitrifying granules.

PMID- 29210705
TI  - Effects of Platelet-Rich Plasma on Pain and Muscle Strength in Patients With Knee
      Osteoarthritis.
AB  - OBJECTIVE: No studies comparing the effects of platelet-rich plasma (PRP)
      injection and placebo injection in bilateral knee osteoarthritis in the same
      patient, or discussing muscle strength after PRP injection, have been published.
      DESIGN: Twenty patients with bilateral knee osteoarthritis were eligible, and 40
      knees were randomized into two groups: PRP (knees [right or left by a coin toss]
      receiving a single intra-articular PRP injection) and saline group (the
      contralateral knee of the same patient, into which single 4-mL intra-articular
      injection of normal saline was administered). The primary outcome measure was
      Western Ontario and McMaster's Universities Osteoarthritis Index and the
      secondary included isokinetic test results. The evaluation was at baseline and at
      2 wks, 1, 3, and 6 mos after injection. RESULTS: The PRP group showed a
      significant reduction in the Western Ontario and McMaster's Universities
      Osteoarthritis Index pain and total scores compared with normal saline group (P <
      0.05). Although a significantly greater percentage of knee strength (extensor >
      flexor) was found in the PRP group during a longer follow-up period, PRP
      treatment resulted in insignificant differences in muscle strength compared with
      normal saline. CONCLUSIONS: Platelet-rich plasma treatment significantly improves
      pain, stiffness, and disability in patients with knee osteoarthritis compared
      with normal saline treatment. Additional strength training is recommended to
      enhance muscle strength recovery.

PMID- 29210706
TI  - Clinical Evidence for Any Effect of Anesthesia on the Developing Brain.
AB  - A recent U.S. Food and Drug Administration warning advised that prolonged or
      repeated exposure to general anesthetics may affect neurodevelopment in children.
      This warning is based on a wealth of preclinical animal studies and relatively
      few human studies. The human studies include a variety of different populations
      with several different outcome measures. Interpreting the results requires
      consideration of the outcome used, the power of the study, the length of exposure
      and the efforts to reduce the confounding effects of comorbidity and surgery.
      Most, but not all, of the large population-based studies find evidence for
      associations between surgery in early childhood and slightly worse subsequent
      academic achievement or increased risk for later diagnosis of a behavioral
      disability. In several studies, the amount of added risk is very small; however,
      there is some evidence for a greater association with multiple exposures. These
      results may be consistent with the preclinical data, but the possibility of
      confounding means the positive associations can only be regarded as weak evidence
      for causation. Finally, there is strong evidence that brief exposure is not
      associated with any long term risk in humans.

PMID- 29210707
TI  - Images in Anesthesiology: Spinal Subdural Hematoma after Spinal Drain for
      Endovascular Thoracic Aortic Aneurysm Repair.

PMID- 29210708
TI  - Takayasu Arteritis and Complete Aortic Arch Branch Vessel Occlusions.

PMID- 29210710
TI  - Hemopericardium and Acute Cardiac Tamponade.

PMID- 29210709
TI  - Alphaxalone Binds in Inner Transmembrane beta+-alpha- Interfaces of
      alpha1beta3gamma2 gamma-Aminobutyric Acid Type A Receptors.
AB  - BACKGROUND: Neurosteroids like alphaxalone are potent anxiolytics,
      anticonvulsants, amnestics, and sedative-hypnotics, with effects linked to
      enhancement of gamma-aminobutyric acid type A (GABAA) receptor gating in the
      central nervous system. Data locating neurosteroid binding sites on synaptic
      alphabetagamma GABAA receptors are sparse and inconsistent. Some evidence points
      to outer transmembrane beta-alpha interfacial pockets, near sites that bind the
      anesthetics etomidate and propofol. Other evidence suggests that steroids bind
      more intracellularly in beta-alpha interfaces. METHODS: The authors created 12
      single-residue beta3 cysteine mutations: beta3T262C and beta3T266C in beta3-M2;
      and beta3M283C, beta3Y284C, beta3M286C, beta3G287C, beta3F289C, beta3V290C,
      beta3F293C, beta3L297C, beta3E298C, and beta3F301C in beta3-M3 helices. The
      authors coexpressed alpha1 and gamma2L with each mutant beta3 subunit in Xenopus
      oocytes and electrophysiologically tested each mutant for covalent sulfhydryl
      modification by the water-soluble reagent para-chloromercuribenzenesulfonate.
      Then, the authors assessed whether receptor-bound alphaxalone, etomidate, or
      propofol blocked cysteine modification, implying steric hindrance. RESULTS:
      Eleven mutant beta3 subunits, when coexpressed with alpha1 and gamma2L, formed
      functional channels that displayed varied sensitivities to the three anesthetics.
      Exposure to para-chloromercuribenzenesulfonate produced irreversible functional
      changes in ten mutant receptors. Protection by alphaxalone was observed in
      receptors with beta3V290C, beta3F293C, beta3L297C, or beta3F301C mutations. Both
      etomidate and propofol protected receptors with beta3M286C or beta3V290C
      mutations. Etomidate also protected beta3F289C. In alpha1beta3gamma2L structural
      homology models, all these protected residues are located in transmembrane beta
      alpha interfaces. CONCLUSIONS: Alphaxalone binds in transmembrane beta-alpha
      pockets of synaptic GABAA receptors that are adjacent and intracellular to sites
      for the potent anesthetics etomidate and propofol.

PMID- 29210712
TI  - Optimizing HIV transition services for young adults.
AB  - PURPOSE OF REVIEW: A total of 1.8 million adolescents live with HIV and
      constitute the only age group in which HIV-associated mortality continues to
      rise. Meeting their healthcare needs as they transition from paediatric services
      to adult care is vital for their own health and in prevention of onward
      transmission to partners and offspring. In this review, we discuss the issues
      around transition, both within HIV health care and the wider transitions
      adolescents negotiate as they move out of childhood and into adult life. RECENT
      FINDINGS: Although transition models vary widely across the globe, the
      difficulties faced in gathering robust outcome data following transition to adult
      care and in linkage between paediatric and adult cohorts are universal. Data are
      particularly sparse for behaviourally infected adolescents outside North America
      and for key population groups. Poorer health outcomes universal to adolescents
      may reflect the complex multisystem developmental transition from childhood-to
      adulthood, of which transition of healthcare services is a small part. SUMMARY:
      The complex needs of this generation are well described and whilst examples of
      good practice are emerging, how best to support their transition to adulthood
      requires carefully tailored studies of cost-effective interventions that can be
      up scaled in resource limited settings.

PMID- 29210711
TI  - An Autopsy Case of Sudden Death in Neurofibromatosis Type 1 With Pheochromocytoma
      and Myocarditis.
AB  - An autopsy case of sudden death in a 33-year-old man with neurofibromatosis type
      1 (von Recklinghausen disease), pheochromocytoma, and myocarditis is reported.
      The decedent was found in his bedroom in cardiopulmonary arrest. Polypoid,
      elastic dermal papules on the neck, chest, abdomen, and back, and flat dark-brown
      macules on the chest and abdomen were observed. Flat, ovoid, dark-brown freckles
      were present in both axillae. Examination of the right adrenal gland revealed a
      tumor measuring 5 cm * 5 cm * 3 cm. Microscopic examination of the myocardium
      revealed moderate neutrophilic and lymphocytic infiltrates. In the right adrenal
      gland, tumor cells contained abundant granular eosinophilic cytoplasm and
      exhibited cell-nesting with an alveolar pattern (Zellballen). Polygonal cells
      were seen together with rich vascular networks. Immunohistochemical analyses
      showed cells diffusely positive for chromogranin A and dopamine beta-hydroxylase.
      Furthermore, blood from the right heart and the right common iliac vein contained
      high concentrations of serum epinephrine, norepinephrine, and dopamine. Death was
      attributed to adrenal crisis: circulatory failure caused by excessive
      catecholamines produced by the pheochromocytoma. In addition, myocarditis, which
      had been induced chronically by catecholamines, would have also contributed
      adversely to the clinical course. Pheochromocytoma and myocarditis should be
      considered when sudden death occurs in the setting of neurofibromatosis type 1.

PMID- 29210713
TI  - Intradermal Proliferative Fasciitis Occurring With Chondrodermatitis Nodularis
      Helicis.
AB  - Nodular fasciitis is a benign myofibroblastic tumor. Its uncommon variant,
      proliferative fasciitis (PF), can present in an even less common intradermal
      form. We report a case of intradermal PF of the ear in a 45-year-old man who
      presented with recurrent episodes of pain and swelling of the lesion. Histologic
      examination showed a dermal, nodular proliferation of ganglion-like basophilic
      fibroblasts with prominent nuclei and nucleoli, admixed with foamy histiocytes
      and areas of spindle cells arranged in intersecting fascicles in a fibromyxoid
      background. Lesional cells stained positive for smooth muscle actin and were
      negative for AE1/AE3, p63, and Melan-A. CD68 highlighted intervening histiocytes.
      We postulate that the underlying chondrodermatitis nodularis helicis was a
      triggering etiology, consistent with the current speculation that intradermal PF
      results from trauma.

PMID- 29210714
TI  - Intertriginous and Seborrheic Dermatitis-Like Lesions in an Endocrine Patient.

PMID- 29210715
TI  - Blistering and Skin Fragility Due to Imatinib Therapy: Loss of Laminin and
      Collagen IV as a Possible Cause of Cutaneous Basement Membrane Instability.
AB  - Imatinib mesylate (Glivec; Novartis AG, Basel, Switzerland) is a tyrosine kinase
      inhibitor which is used in the treatment of oncologic diseases like chronic
      myeloid leukemia and gastrointestinal stroma tumor (GIST). Among cutaneous side
      effects, bullous reactions are rare. The authors describe the case of a 66-year
      old woman developing blistering and skin fragility on her hands, foot, lower
      legs, and back after intake of imatinib for treatment of GIST. Biopsy showed
      vacuolar alteration at the dermoepidermal junction (DEJ) associated with a few
      lymphocytes and a subepidermal blister. The upper papillary dermis below the
      vacuolar alteration and below the blister showed hyalinization and loss of
      elastic microfibrils. Direct immunofluorescence was negative for deposits of
      immunoglobulins. Immunofluorescence on cryosections revealed loss of laminin and
      collagen IV in vacuoles at the DEJ. Electron microscopy showed dissolution of
      lamina lucida and lamina densa of the basement membrane below as well as next to
      the vacuoles and blister. In conclusion, the authors present the first patient
      with GIST with blistering and skin fragility due to imatinib therapy. As a
      pathophysiological explanation the authors propose loss of laminin and collagen
      IV at the DEJ leading to basement membrane instability and blistering. This case
      also suggests additional features reminiscent of lichen sclerosus induced by
      imatinib, a drug which is actually known for its antifibrotic effects.

PMID- 29210716
TI  - Relationship Between Pityriasis Lichenoides and Mycosis Fungoides: A
      Clinicopathological, Immunohistochemical, and Molecular Study.
AB  - BACKGROUND: Several cases of pityriasis lichenoides (PL) have been reported to
      evolve into mycosis fungoides (MF). OBJECTIVE: To elucidate clues to this
      progression. METHODS: Fifty-eight patients with PL between 2000 and 2013 (follow
      up: 3-16 years, average: 8.3). RESULTS: A total of 3 (5.2%) of the 58 patients
      with PL developed MF after 3-11 years of prolonged clinical course. Papules and
      small plaques characterized PLs, and patches and larger plaques subsequent MFs. A
      total of 35 of 41 (85%) followed up non-MF associated patients with PL reported
      lasting complete remissions. Histopathologically, apoptotic keratinocytes
      disappeared mostly or completely in subsequent MFs. The presence of
      epidermotropism, folliculotropism, and epidermal lymphocytic nuclear atypia in
      PLs was not predictive of MF. CD8 cells were the dominant intraepidermal
      lymphocytes in the 3 PLs but remained so in only 1 subsequent MF. CD7 lymphocytes
      decreased substantially in 2 MFs, and lymphocytic nuclear atypia increased
      markedly in 1. T-cell receptor gene rearrangement studies demonstrated clonal
      populations in 1 of 2 studied PLs and in all 3 subsequent MFs. CONCLUSIONS: A few
      PLs may evolve into MF. Prolonged clinical course, appearance of patches and
      larger plaques, markedly increased lymphocytic nuclear atypia, marked diminution
      of apoptotic keratinocytes and CD7 and CD8 lymphocytes, and clonal T-cell
      receptor gene rearrangement may serve as clues.

PMID- 29210717
TI  - Quality of life outcomes after endoscopic approaches to intracranial tumors.
AB  - PURPOSE OF REVIEW: To review the literature on quality of life (QOL) in
      endoscopic approaches to anterior and central intracranial skull-base disease. As
      endoscopic surgical techniques have gained widespread acceptance and
      complications and morbidity remain low and comparable with microscopic and open
      approaches, a shift to focusing on patients' perception of their own well being
      as an important outcome parameter has been made. In addition to the traditional
      measurements of surgical outcomes (extent of resection, recurrence rate,
      morbidity, survival, and complication rate), the success of a surgery can now be
      assessed using QOL measures. RECENT FINDINGS: The main tools for assessing QOL in
      endoscopic skull-base surgery (anterior skull-base questionnaire and 22-item
      sinonasal outcome test) were not specifically designed for endoscopic skull-base
      approaches, and recently, a new tool was introduced and validated, the skull-base
      inventory, adding to our armamentarium, but it has not yet been widely employed.
      Endoscopic skull-base surgery leads to improved or sustained long-term QOL
      overall but it is significantly influenced by tumor disease. Specific endoscopic
      surgical technique (such as nasoseptal flap closure) appears to have less impact
      on QOL. SUMMARY: It is becoming critical to assess therapeutic interventions in
      terms of impact on a patient's QOL. QOL can be useful in comparing efficacy of
      surgical interventions, and in the future, it will likely become a reportable
      indicator of surgical outcome and guide our surgical technique recommendations.
      Large-scale prospective multicenter trials would be beneficial.

PMID- 29210718
TI  - Successful Treatment of Idiopathic Intractable Hiccup With Cisatracurium Under
      Intravenous General Anesthesia: A Case Report.
AB  - We report the successful treatment of idiopathic intractable hiccups with
      cisatracurium under intravenous general anesthesia. The patient had a history of
      hiccups for 19 years that were refractory to a variety of treatments. When his
      hiccups were accompanied by vomiting, insomnia, shortness of breath, and poor
      oral intake for 9 days, he sought relief. We administered a nondepolarizing
      muscle relaxant, cisatracurium, during total intravenous anesthesia, to stop the
      hiccups. The duration of the anesthetic was determined by the time it took for
      the patient to recover from the neuromuscular blockade without reversal the
      cisatracurium. On emergence he had no hiccups. When the hiccups recurred 2 weeks
      later after a big meal, we repeated the procedure with success. He has now been
      hiccup free for at least 6 months.

PMID- 29210719
TI  - Neuromodulatory Burst Therapy for Agent Orange-Induced Peripheral Neuropathy: A
      Case Report.
AB  - The prevalence of neuromuscular diseases and peripheral neuropathies in veterans
      exposed to Agent Orange (AO) is particularly high. Pharmacologic management has
      not been effective for these patients. Burst therapy spinal cord stimulation
      (SCS), recently approved for use in the United States, has had demonstrable
      success in both Europe and Australia. We present a patient with AO-induced
      peripheral neuropathy who was successfully treated with burst SCS. To our
      knowledge, this is the first report describing the use of burst SCS for treatment
      of peripheral neuropathy related to AO exposure.

PMID- 29210724
TI  - Anesthetic Management of a Pacemaker With a Rate Drop Response Setting: A Case
      Report.
AB  - Permanent pacemakers are used for a variety of conditions and are commonly
      encountered in the perioperative period. This report describes the anesthetic
      management of a patient with a permanent pacemaker with a rate drop response
      (RDR) who presented for a laparoscopic left adrenalectomy. The RDR setting is a
      novel pacemaker mode often used in patients with a history of vasovagal syncope.
      There are no previous reports describing the anesthetic management of such a
      pacemaker. This case report describes the features of the RDR setting with the
      goal of educating clinicians who may encounter patients with this type of
      pacemaker. The patient described in this case report had large swings in blood
      pressure intraoperatively due to the natural function of his pacemaker. This
      report highlights the importance of understanding pacemaker modes in patients
      about to undergo surgery, especially because pacemaker functions are becoming
      increasingly sophisticated and more personalized to meet patients' specific
      needs.

PMID- 29210727
TI  - Regulatory T cells: from the bench to the clinic and back.
AB  - PURPOSE OF REVIEW: The main objective of this review is to briefly highlight how
      we gradually came to understand regulatory T cells (Tregs) and forkhead box p3
      (FoxP3) biology, including their function and regulation. We will also discuss
      how this knowledge is being translated into the clinical setting and the
      significant challenges that need to be overcome. RECENT FINDINGS: CD4FoxP3 Tregs
      are key players in immune regulation. Their deficiency and dysfunction have been
      implicated in the pathogenesis of many autoimmune diseases. This has led towards
      extensive work across the years to figure out the biology and suppressive
      mechanisms of these cells. Furthermore, Tregs' ability to suppress immune
      responses makes the idea of their utilization in adoptive immunotherapy
      appealing. Work has been underway to establish ideal methods to integrate Tregs
      into the management of autoimmune diseases and alloimmunity, either by treatment
      with IL-2 or infusion of ex-vivo expanded Tregs. Despite Tregs' scarcity and
      increased tendency for Activation-induced cell death, many groups have developed
      effective methods to expand them ex vivo. SUMMARY: Although clinical trials are
      ongoing to test the safety and efficacy of regulatory cells in transplant
      recipients, it is vital to continue exploring the cellular and molecular
      mechanisms that control their stability and homeostasis.

PMID- 29210729
TI  - Health Humanities and Medical Education: Joined by a Common Purpose.

PMID- 29210728
TI  - Are donor lymphocytes a barrier to transplantation tolerance?
AB  - PURPOSE OF REVIEW: Following solid organ transplantation (SOT), populations of
      donor lymphocytes are frequently found in the recipient circulation. Their impact
      on host alloimmunity has long been debated but remains unclear, and it has been
      suggested that transferred donor lymphocytes may either promote tolerance to the
      graft or hasten its rejection. We discuss possible mechanisms by which the
      interaction of donor passenger lymphocytes with recipient immune cells may either
      augment the host alloimmune response or inhibit it. RECENT FINDINGS: Recent work
      has highlighted that donor T lymphocytes are the most numerous of the donor
      leukocyte populations within a SOT and that these may be transferred to the
      recipient after transplantation. Surprisingly, graft-versus-host recognition of
      major histocompatibility complex class II on host B cells by transferred donor
      CD4 T cells can result in marked augmentation of host humoral alloimmunity and
      lead to early graft failure. Killing of donor CD4 T cells by host natural killer
      cells is critical in preventing this augmentation. SUMMARY: The ability of
      passenger donor CD4 T cells to effect long-term augmentation of the host humoral
      alloimmune response raises the possibility that ex-vivo treatment or modification
      of the donor organ prior to implantation may improve long-term transplant
      outcomes.

PMID- 29210730
TI  - "Social Contract" Remains a Useful Metaphor.

PMID- 29210731
TI  - In Reply to Cruess et al.

PMID- 29210732
TI  - Implementing the Charter on Professionalism.

PMID- 29210733
TI  - In Reply to Griffith.

PMID- 29210734
TI  - International Medical Graduates Who Have Been Disciplined: Further Causes and
      Methods to Improve Quality of Care.

PMID- 29210736
TI  - When and How Do We Teach Cultural Awareness?

PMID- 29210735
TI  - In Reply to Hyder.

PMID- 29210737
TI  - In Reply to Weissman.

PMID- 29210738
TI  - Addressing Military Cultural Competence in Medical Education.

PMID- 29210739
TI  - In Reply to Mathewson-Chapman and Chapman.

PMID- 29210740
TI  - What Are the Opportunity Costs of Self-Financing Medical Education?

PMID- 29210741
TI  - In Reply to Nguyen and Makam.

PMID- 29210742
TI  - Making a Case for Case Reports.

PMID- 29210743
TI  - In Reply to Steinhilber et al.

PMID- 29210745
TI  - Boxed In: Lessons From the Margins of Medical Student Comics.

PMID- 29210744
TI  - Artist's Statement: First Position.

PMID- 29210746
TI  - Commentary on Boxed In: Lessons From the Margins of Medical Student Comics.

PMID- 29210747
TI  - 2017 Hope Babette Tang Humanism in Healthcare Essay Contest: First Place: Eric.

PMID- 29210748
TI  - Empathy Found Me.

PMID- 29210749
TI  - Pulmonary rehabilitation for patients with acute chronic obstructive pulmonary
      disease exacerbations: is the evidence strengthening?
AB  - PURPOSE OF REVIEW: This manuscript aims to review the most recent evidence about
      the benefits of early pulmonary rehabilitation commenced during an acute
      exacerbation in people with COPD (AECOPD). RECENT FINDINGS: A number of RCTs and
      an observational study, published between 2015 and 2017, have used different
      exercise interventions compared with usual medical care in people with moderate
      to-severe COPD during an AECOPD. The results show short-term improvement in
      walking distance, muscle strength, quality of life and anxiety and depression.
      SUMMARY: The evidence about early rehabilitation during AECOPD is growing in
      strength; however, the outcomes and interventions that were used in the RCTs
      varied from study to study. Unlike pulmonary rehabilitation for people with
      stable COPD, there is no ideal model of early rehabilitation for people with
      AECOPD and little information about long-term benefits, for example, attendance
      at outpatient-based pulmonary rehabilitation and hospital admissions and length
      of stay. Because of the risks of deconditioning during an AECOPD and the related
      healthcare costs, early rehabilitation should commence at the bedside. However,
      more research is required determine the best way to provide early rehabilitation
      for people with AECOPD.

PMID- 29210750
TI  - Insights about the economic impact of chronic obstructive pulmonary disease
      readmissions post implementation of the hospital readmission reduction program.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) affects over 12
      million adults in the United States and is the third leading cause of 30-day
      readmissions. COPD is costly with almost $50 billion in direct costs annually.
      Total COPD costs can be up to double the identified direct costs because of
      comorbid disease and numerous indirect costs such as absenteeism. Acute
      exacerbations of COPD (AECOPD) are responsible for up to 70% of COPD-related
      healthcare costs; hospital readmissions alone account for over $15 billion
      annually. In this review, we aim to describe insights about the economic impact
      of COPD readmissions based on articles published over the last 18 months. RECENT
      FINDINGS: Interventions aimed at reducing readmission, particularly those using
      interdisciplinary teams with bundled care interventions, were uniformly
      successful at improving the quality of care provided and demonstrating improved
      process measures. However, success at reducing readmissions and cost savings
      based on these interventions varied across the studies. SUMMARY: The literature
      to date points to factors and conditions that may place patients at higher risk
      of readmissions and may lead to higher costs. Interventions aimed at reducing
      readmissions after index admissions for AECOPD have demonstrated variable
      results. Most interventions did not reflect cost-based analyses.

PMID- 29210751
TI  - Chronic obstructive pulmonary disease and lung cancer: inter-relationships.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a well
      established risk factor for lung cancer. Newer studies reveal a myriad of other
      mechanisms, some proven and some putative, which may contribute to their
      association. RECENT FINDINGS: There is an ever-growing bundle of evidence that
      suggests a close association between persistent chronic inflammation and lung
      cancer. A few potential targets of genetic susceptibility locus for COPD and lung
      cancer have been suggested. Better characterization of immune dysregulation and
      identification of signaling pathways may assist the development of strategies to
      reduce risk of developing lung cancer in patients with COPD. Current lung cancer
      screening strategies may exclude some patients at high risk of having lung
      cancer. Prospective studies indicate that a screening criterion that includes
      variables reflecting the severity of COPD may increase the sensitivity of the
      screening program and reduce 'over-diagnosis bias' of indolent lung cancers.
      Examples of such variables include the emphysema score generated from computed
      tomography scans and diffusion capacity for carbon monoxide derived from lung
      function tests. SUMMARY: A better understanding of the inter-relationship between
      lung cancer pathogenesis and COPD has been described recently. Improving lung
      cancer screening strategies by incorporating markers of COPD severity has
      recently been proposed.

PMID- 29210752
TI  - Lactobacillus casei beneficially modulates immuno-coagulative response in an
      endotoxemia model.
AB  - : The current study aims at evaluating the effect of the oral administration of
      Lactobacillus casei CERELA (CRL) 431 on parameters implicated in inflammation
      coagulation interaction using a model of acute inflammation induced by
      lipopolysaccharide (LPS) in mice. Six-week-old Balb/c mice were treated with L.
      casei for 5 consecutive days. Then treated and untreated mice received an LPS
      injection (L. casei + LPS and LPS groups, respectively). Liver and kidney were
      removed, blood samples were obtained, and hemostatic and inflammatory parameters
      were evaluated at different times post LPS injection. Preventive L. casei
      administration induced a significant decrease in proinflammatory TNF-alpha and IL
      6 cytokines by decreasing tissue factor expression in liver and kidney. Moreover,
      the lower expression of tissue factor in the L. casei + LPS group led to a lower
      activation of the coagulation system, which was observed by the fast systemic
      restoration of factors VII and V coagulation factors and antithrombin levels.
      This study highlights the capacity of L. casei to modulate the hemostatic
      unbalance in an acute endotoxemia model. Our findings showed the ability of L.
      casei CRL 431 to regulate the immuno-coagulative response. This fact could be
      helpful to propose new adjunctive strategies addressed to the restoration of
      physiological anticoagulant mechanisms in sepsis patients.

PMID- 29210753
TI  - Faculty Support for Self-Directed Learning in Internal Medicine Residency: A
      Qualitative Study Using Grounded Theory.
AB  - PURPOSE: Self-directed learning (SDL) is part of residency training, which
      residents desire guidance in implementing. To characterize SDL within the
      clinical context, this study explored residents' perceptions of faculty members'
      role in promoting and supporting resident SDL. METHOD: Using a constructivist
      grounded theory approach, the authors conducted seven focus groups with 46
      internal medicine residents at the Mayo Clinic Internal Medicine Residency
      Program from October 2014 to January 2015. Focus group transcripts were
      deidentified and processed through open coding and analytic memo writing. Guided
      by a previously developed SDL model, data were analyzed regarding faculty member
      involvement in resident SDL. Themes were organized and patterns were discussed at
      team meetings, with constant comparison with new data. Trustworthiness was
      established using two member-check sessions. RESULTS: The authors identified
      themes within the categories of faculty guidance for SDL, SDL versus other
      directed learning (ODL), and faculty archetypes for supporting SDL. Clinical
      teachers play a key role in facilitating resident SDL and can provide guidance at
      each step in the SDL process. Residents discussed the distinction between SDL and
      ODL, highlighting the integrated nature of learning and interplay between the two
      approaches to learning. Residents identified themes relating to three archetypal
      approaches faculty implement to support resident SDL in the clinical environment
      (directed, collaborative, and role model SDL), with benefits and challenges of
      each approach. CONCLUSIONS: This study underscores the importance of external
      guidance for resident SDL and expands on approaches faculty members can use to
      support SDL in the clinical context.

PMID- 29210754
TI  - Managing Multiplicity: Conceptualizing Physician Cognition in Multipatient
      Environments.
AB  - PURPOSE: Emergency physicians (EPs) regularly manage multiple patients
      simultaneously, often making time-sensitive decisions around priorities for
      multiple patients. Few studies have explored physician cognition in multipatient
      scenarios. The authors sought to develop a conceptual framework to describe how
      EPs think in busy, multipatient environments. METHOD: From July 2014 to May 2015,
      a qualitative study was conducted at McMaster University, using a think-aloud
      protocol to examine how 10 attending EPs and 10 junior residents made decisions
      in multipatient environments. Participants engaged in the think-aloud exercise
      for five different simulated multipatient scenarios. Transcripts from recorded
      interviews were analyzed inductively, with an iterative process involving two
      independent coders, and compared between attendings and residents. RESULTS: The
      attending EPs and junior residents used similar processes to prioritize patients
      in these multipatient scenarios. The think-aloud processes demonstrated a similar
      process used by almost all participants. The cognitive task of patient
      prioritization consisted of three components: a brief overview of the entire
      cohort of patients to determine a general strategy; an individual chart review,
      whereby the participant created a functional patient story from information
      available in a file (i.e., vitals, brief clinical history); and creation of a
      relative priority list. Compared with residents, the attendings were better able
      to construct deeper and more complex patient stories. CONCLUSIONS: The authors
      propose a conceptual framework for how EPs prioritize care for multiple patients
      in complex environments. This study may be useful to teachers who train
      physicians to function more efficiently in busy clinical environments.

PMID- 29210755
TI  - Recruitment of Dual-Career Academic Medicine Couples.
AB  - Today it is not uncommon to discover that a candidate for a faculty position has
      a partner or spouse who is also an academician, adding complexity to the
      recruitment process. Here, the authors address two practical obstacles to the
      recruitment of faculty who have an academic partner: dual recruitment and
      conflict of interest. The authors have found that tandem recruitment works best
      when suitable positions for both spouses are first identified so that recruitment
      can proceed synchronously. This approach decreases misperceptions of favoritism
      toward either's candidacy. Managing conflict of interest, generated by the
      appointment of one spouse in a supervisory position over the other, requires a
      proactive, transparent, well-designed plan. After canvassing human resource
      policies and conducting interviews with national academic leaders, the authors
      have developed an administrative structure that places "key" decisions (hiring
      and retention; promotion and tenure; salary, bonuses, and benefits; performance
      evaluations; and disciplinary matters) regarding the supervised spouse in the
      jurisdiction of an alternative administrator or committee. The authors also offer
      suggestions both for mitigating misperceptions of bias in day-to-day decisions
      and for the support and mentoring of the supervised partner or spouse.

PMID- 29210756
TI  - The Survey Checklist (Manifesto).
AB  - Checklists can mitigate a multitude of high-cost mistakes in fields ranging from
      surgery to aviation. As part of a standard protocol, checklists may provide many
      benefits, including improved equity and communication among team members and more
      efficient integration of different processes during complex tasks. Mostly,
      though, checklists serve as easy, efficient means to remind professionals of what
      they already know but can easily forget. By improving processes, checklists can
      reduce procedural errors, miscommunications, and even deaths. Although the stakes
      of writing a survey are rarely as high as they are for performing surgery or
      piloting a plane, checklists can improve the quality of surveys in medical
      education. In this Perspective, the authors propose a survey checklist to serve
      the same core function as surgical checklists-to reduce error. That is, a survey
      checklist can help medical education practitioners and researchers gather more
      accurate responses. Designers can use the checklist in the appendix to guide item
      creation processes or to help evaluate the quality of existing surveys. The
      checklist focuses on formulating items, crafting response options, and
      formatting/organizing the whole survey.

PMID- 29210757
TI  - Challenges in Surgical Care of High Risk Newborns.

PMID- 29210758
TI  - NANN Celebrates Neonatal Nurses Day.

PMID- 29210759
TI  - Nursing Care of Infants with a Ventriculoperitoneal Shunt.

PMID- 29210760
TI  - A Pilot Study of Responses to Suctioning Among Neonates on Bubble Nasal
      Continuous Positive Airway Pressure.
AB  - BACKGROUND: Maintenance of a patent airway while the neonate is on nasal
      continuous positive airway pressure (nasal CPAP) requires vigilant monitoring and
      oral/nasopharyngeal suctioning. Currently, no evidence-based guidelines for safe
      suctioning in neonates while on bubble nasal CPAP have been published. PURPOSE:
      (1) To characterize the clinical and behavioral responses of neonates on bubble
      nasal CPAP in a level III neonatal intensive care unit following routine oral and
      nasopharyngeal suctioning. METHODS: This pilot study has a 1-sample within
      subject repeated-measures design in which neonates (N = 16) served as their own
      control. Data on a neonate's physiological and behavior measures (heart rate,
      respiratory rate, oxygen saturation [SaO2], and Premature Infant Pain Profile
      [PIPP] score) were collected before, during, and after the completion of
      suctioning sequence. FINDING/RESULTS: A total of 16 neonates with a mean
      gestational age of 29.76 weeks and an average day of life of 3.4 were enrolled.
      The infant's heart rates did not differ significantly (P = .51) across the
      suctioning sequence. There were no statistical significant changes in the average
      respiratory rate across the suctioning sequences (P = .79). SaO2 demonstrated a
      drop between baseline and after each suctioning (P < .001). The PIPP score
      demonstrated a precipitous increase throughout the procedure (P < .001). On
      average, it took 9.5 seconds (SD = 4.9) to complete the suctioning sequences.
      IMPLICATIONS FOR PRACTICE: Our results suggest that the guideline tested is safe
      and tolerated by infants. IMPLICATIONS FOR RESEARCH: This guideline should be
      tested in a larger sample and with neonates on other nasal CPAP systems.

PMID- 29210761
TI  - Foreword.

PMID- 29210762
TI  - Decentralization: The Corridor Is the Problem, Not the Alcove.
AB  - There is controversy today about whether decentralized intensive care unit (ICU)
      designs featuring alcoves and multiple sites for charting are effective. There
      are issues relating to travel distance, visibility of patients, visibility of
      staff colleagues, and communications among caregivers, along with concerns about
      safety risk. When these designs became possible and popular, many ICU designs
      moved away from the high-visibility circular, semicircular, or box-like shapes
      and began to feature units with more linear shapes and footprints similar to
      acute bed units. Critical care nurses on the new, linear units have expressed
      concerns. This theory and opinion article relies upon field observations in
      unrelated research studies and consulting engagements, along with material from
      the relevant literature. It leads to a challenging hypothesis that criticism of
      decentralized charting alcoves may be misplaced, and that the associated problem
      may stem from corridor design and unit size in contemporary ICU design. The
      authors conclude that reliable data from research investigations are needed to
      confirm the anecdotal reports of nurses. If problems are present in current
      facilities, organizations may wish to consider video monitoring, expanded
      responsibilities in the current buddy system, and use of greater information
      sharing during daily team huddles. New designs need to involve nurses and
      carefully consider these issues.

PMID- 29210763
TI  - Evaluating Nurses' Perception of Patient Safety Design Features in Intensive Care
      Units.
AB  - A methodological study was conducted to test the validity and reliability of the
      patient safety (PS) scale developed by Rashid (2007) for evaluating nurses'
      perception of adult intensive care unit (ICU) design features related to patient
      safety. Data for the study were collected using a Web-based survey instrument. A
      link to the survey instrument was posted on the Web site of American Association
      of Critical-Care Nurses (AACN) for ICU nurses in different US states to
      participate. A sample of 587 valid responses was divided into 2 halves for cross
      validation. The first half of the sample was used for exploratory factor analysis
      and the second half for confirmatory factor analysis. This method was applied to
      identify any latent factor structure in the PS scale. Based on the factor
      analyses, 4 relevant PS subscales-Efficient Work Process, Patient Room,
      Accessibility and Visibility, and Maintain Sterility-were identified. These PS
      subscales were used to investigate whether ICU unit characteristics, nurse
      characteristics, and hospital type affected nurses' perception of ICU design
      features in relation to patient safety. The study shows that nurses' perception
      of ICU design features related to patient safety can be influenced by such
      factors as nurse characteristics and unit characteristics. When using the scales,
      therefore, the designers can be aware of the influence of these external factors
      on nurses' perception. It is hoped that the PS subscales evaluating nurses'
      perception of ICU physical environmental features related to patient safety would
      help designers and health care personnel make better ICU design choices.

PMID- 29210764
TI  - Deriving Information Requirements for a Smart Nursing System for Intensive Care
      Units.
AB  - The workplace environment for intensive care nursing is highly stressful, with
      long working hours and a dynamic workload that may induce fatigue. The resulting
      stress and fatigue may reduce nurses' efficiency and may contribute to medical
      errors. A smart wearable system is being designed to help nurses who experience
      high levels of stress and fatigue at work. This article documents the systematic
      process of deriving information requirements from 2 focus groups conducted
      separately with nurses and nurse managers working in various Southeastern Texas
      hospitals. While nurses expected functionality such as memory aid tools, health
      assessment, and stress-reducing exercises, nurse managers expected information
      about the overall status of the unit's fatigue/stress levels as well as nurses'
      communication and movement patterns. The derived information requirements will
      act as an objective assessment of needs and would set the stage for the design of
      a stress-monitoring tool.

PMID- 29210765
TI  - Environmental Infection Prevention: Priorities of Patient Safety Collaboration.
AB  - Although progress has been made in decreasing health care-associated infections
      (HAI) in intensive care unit (ICU) patients, there has been an increase in HAI
      caused by drug-resistant pathogens, particularly those that contaminate the
      environment such as methicillin-resistant Staphylococcus aureus, vancomycin
      resistant Enterococcus, Pseudomonas spp, Acinetobacter spp, and Clostridium
      difficile. The ICU environment including sinks and medical equipment has been
      identified as being at risk for contamination and associated with cross
      transmission of pathogens between the health care provider, the environment, and
      the patient. This article addresses the role of the ICU nurse as a team
      facilitator collaborating with environmental services, infection preventionists,
      and others to influence ICU design during preconstruction planning and unit
      environmental hygiene after construction to promote patient safety and prevent
      HAI associated with contaminated environments and equipment.

PMID- 29210766
TI  - Tele-ICU and Patient Safety Considerations.
AB  - The tele-ICU is designed to leverage, not replace, the need for bedside clinical
      expertise in the diagnosis, treatment, and assessment of various critical
      illnesses. Tele-ICUs are primarily decentralized or centralized models with
      differing advantages and disadvantages. The centralized model has sufficiently
      powered published data to be associated with improved mortality and ICU length of
      stay in a cost-effective manner. Factors associated with improved clinical
      outcomes include improved compliance with best practices; providing off-hours
      implementation of the bedside physician's care plan; and identification of and
      rapid response to physiological instability (initial clinical review within 1
      hour) and rapid response to alerts, alarms, or direct notification by bedside
      clinicians. With improved communication and frequent review of patients between
      the tele-ICU and the bedside clinicians, the bedside clinician can provide the
      care that only they can provide. Although technology continues to evolve at a
      rapid pace, technology alone will most likely not improve clinical outcomes.
      Technology will enable us to process real or near real-time data into complex and
      powerful predictive algorithms. However, the remote and bedside teams must work
      collaboratively to develop care processes to better monitor, prioritize,
      standardize, and expedite care to drive greater efficiencies and improve patient
      safety.

PMID- 29210767
TI  - Informatics for the Modern Intensive Care Unit.
AB  - Advanced informatics systems can help improve health care delivery and the
      environment of care for critically ill patients. However, identifying, testing,
      and deploying advanced informatics systems can be quite challenging. These
      processes often require involvement from a collaborative group of health care
      professionals of varied disciplines with knowledge of the complexities related to
      designing the modern and "smart" intensive care unit (ICU). In this article, we
      explore the connectivity environment within the ICU, middleware technologies to
      address a host of patient care initiatives, and the core informatics concepts
      necessary for both the design and implementation of advanced informatics systems.

PMID- 29210768
TI  - Safety and Security Concerns of Nurses Working in the Intensive Care Unit: A
      Qualitative Study.
AB  - Intensive care units (ICUs) exist to serve as a safe place for critically ill
      patients to receive care from skilled practitioners. In this qualitative study,
      ICU nurses shared their perspectives on elements that promote safety and security
      on their units. After obtaining institutional review board approval, participants
      participated in telephone interviews with a nurse researcher who has experience
      as a bedside ICU nurse. Five categories and 14 themes were identified and then
      confirmed using member checking. Results indicate that participants prefer to
      provide care in ICUs with no more than 12 to 14 beds and provide the following:
      visibility of patients and coworkers; more than 1 way to exit; and can be locked
      in case of emergency or threat. Nearly all respondents mentioned adequate
      staffing as the most important attribute of a safe, secure care environment for
      patients and families. More research is needed to identify design features that
      make the most impact on providing a safe, secure ICU environment.

PMID- 29210769
TI  - Direct Observation of Medication Errors in Critical Care Setting: A Systematic
      Review.
AB  - Medication errors continue to be an issue for the critically ill and are costly
      to both patients and health care facilities. This article reviews published
      research about these errors and reports results of observational studies. The
      types of errors, incidence, and root causes have been considered along with
      adverse consequences. The implications for bedside practice as a result of this
      review are fairly straightforward. Medication errors are happening at an alarming
      rate in the critical care environment, and these errors are preventable. It is
      imperative that all personnel respect and follow established guidelines and
      procedural safeguards to ensure flawless drug delivery to patients.

PMID- 29210770
TI  - In Vitro Generation of Glucose-Responsive Insulin-Secreting Cells from PDX1
      Overexpressing Human-Induced Pluripotent Stem Cell Derived from Diabetic Patient.
AB  - Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing
      transcription factor family, is a key transcription factor for pancreas
      development and mature beta-cell function. In this study, induced overexpression
      of PDX1 resulted in producing susceptible cells for pancreatic differentiation
      and was well beneficial to enhance beta-cell production, maturation, function,
      and survival. Induced PDX1 overexpression in harmony with a set of signaling
      molecules involves in guiding the signaling pathways toward pancreas development,
      leaded to high-efficient in vitro generation of ectopic insulin-producing cells
      (IPCs) with the effectively reduced number of polyhormonal cells and increased
      number of insulin (INS) single-positive cells. This strategy yielded 85.61%
      glucose-responsive insulin-positive cells in vitro, which was seven times higher
      than the basal level, and electron microscopy images revealed the presence of
      mature beta-cell secretory granules. The generation of glucose-responsive insulin
      secreting beta-like cells from human-induced pluripotent stem cells (hiPSCs) in
      vitro would provide a promising approach to produce an unprecedented cell source
      for cell transplantation therapy in diabetes without the ethical obstacle of
      embryonic stem cells and would bypass immune rejection. These cells are an
      invaluable source for disease modeling, drug discovery, and pharmacogenomics
      studies as well.

PMID- 29210771
TI  - Effect of Inhaled Nitric Oxide on Hemodynamics in Lambs with 11/2 Ventricle
      Circulation.
AB  - Inhaled nitric oxide (NO) is widely used to treat postoperative pulmonary
      hypertension in congenital heart disease. It is believed that NO increases
      cardiac output (CO) by decreasing pulmonary vascular resistance (PVR), leading to
      increased left ventricular preload. However, the effect of NO on CO in patients
      with 11/2 ventricle circulation remains unclear. To evaluate this, a superior
      cavopulmonary (SCP) shunt was constructed in 10 juvenile sheep. A PTFE graft was
      inserted between the superior vena cava (SVC) and the main pulmonary artery (PA).
      The SVC was clamped at the right atrial junction to establish a 11/2 ventricle
      circulation. Flows, pressures, and arterial blood gases were recorded before and
      during inhalation of NO. Mean arterial pressure (46.6 +/- 5.4 to 44.6 +/- 5.9 mm
      Hg; p = 0.06) and left atrial pressure (4.0 +/- 2.5 to 4.0 +/- 2.3 mm Hg; p =
      1.0) did not change. Mean PA pressure (13.6 +/- 2.4 to 11.7 +/- 2.9 mm Hg; p =
      0.006) and PVR (5.47 +/- 2.99 to 4.54 +/- 2.61 Wood Units; p = 0.037) decreased
      significantly. SVC flow (24.8 +/- 11.3 to 22.0 +/- 9.7 ml/min/kg; p = 0.09) did
      not change, and CO decreased (140.2 +/- 37.2 to 132.1 +/- 39.2 ml/min/kg; p =
      0.033). Arterial PO2 improved (103.72 +/- 29.30 to 132.43 +/- 47.02 mm Hg; p =
      0.007). In this 11/2 ventricle model, NO surprisingly decreased cardiac output
      (CO) and did not increase left ventricular preload.

PMID- 29210772
TI  - Bleeding Complication Rates Are Higher in Females after Continuous-Flow Left
      Ventricular Assist Device Implantation.
AB  - The aims of this analysis were to characterize the burden and timing of bleeding
      events in females versus males on left ventricular assist device (LVAD) support.
      A single-center retrospective review of 375 patients receiving continuous-flow
      LVADs was performed. Bleeding events included gastrointestinal, naso
      oropharyngeal, gynecologic (GYN), intracranial hemorrhage (ICH), and mediastinal
      bleeding. Cox hazard ratios (HRs) [95% CI] and incident event rates for females
      versus males were calculated. Eighty-four females (22%) and 291 males (78%)
      received an LVAD. There were 189 patients with 406 bleeding events over a median
      399 days of support. Two-year freedom from bleeding was 33 +/- 6.2% in females
      and 46 +/- 3.7% in males (p = 0.027). Correlates of bleeding included female sex
      (adjusted HR = 1.6 [1.1-2.2]) and older age (adjusted HR = 1.2 [1.1-1.3] per 10
      years). There was no sex-associated difference in 30 day mediastinal bleeding
      (males 12%; females 16% at 30 days; overall p = 0.35), but incident event rates
      for overall bleeding and naso-oropharyngeal bleeding were higher in females (p <
      0.05) and trends were noted in ICH (eppy: 0.06 male vs. 0.10 female, p = 0.14).
      Eight females (10%) experienced 12 GYN bleeding events; five required surgical
      intervention. In summary, females had a 60% higher hazard of bleeding than males
      with significant morbidity encountered from mucosa (including vaginal) bleeding.
      Future large device studies should be inclusive of sex-specific outcomes.

PMID- 29210773
TI  - Do Psychosocial Factors Have Any Impact on Outcomes After Left Ventricular Assist
      Device Implantation?
AB  - Psychosocial factors have been show to impact survival and outcomes in a number
      of different diseases, including heart failure and patients receiving heart
      transplantation. With the increasing utilization of these devices, it is
      important to identify risk factors that could impact post-left ventricular assist
      device (LVAD) outcomes. This study was a single center, retrospective analysis of
      238 patients who underwent implantation of a LVAD between July 27, 2004, and July
      21, 2016, at The University of Nebraska Medical Center. Data collected include
      length of stay, number of readmission, alive status at 30 days, 180 days, and 1
      year, as well as multiple psychosocial factors including history of drug abuse,
      history of alcohol abuse, history of noncompliance, history of anxiety, and
      history of depression, among others. Outcomes were calculated using univariate
      and multivariate analyses with SAS Version 9.4. None of the psychosocial factors
      assessed in this study showed statistical significance in predicting 30 day or 6
      month mortality, but patients who smoked at the time of admission for LVAD
      implantation had higher mortality at 1 year (odds ratio 4.6, 95% confidence
      interval, 1.226-15.898, p = 0.011.) Patients with a diagnosis of depression had
      higher numbers of readmissions compared with those without depression (p = 0.048)
      with the number of readmissions further increased in patients with a diagnosis of
      both depression and anxiety (p = 0.0074). Psychosocial determinants do not appear
      to have a significant effect on mortality, but can result in increased risk of
      readmission if not adequately addressed before implantation and continually
      monitored postimplantation.

PMID- 29210774
TI  - Liberal Right Ventricular Assist Device Extracorporeal Membrane Oxygenation
      Support for Right Ventricular Failure after Implantable Left Ventricular Assist
      Device Placement.
AB  - Refractory right ventricular failure (RVF) after implantation of left ventricular
      assist device (LVAD) is a dramatic complication. The addition of right
      ventricular assist device (RVAD) may improve RV recovery and lead to improve
      outcomes. From February 2012 to September 2014, 44 patients received a HeartMate
      II. These patients were retrospectively compared in two groups according to early
      liberal implantation of an extracorporeal membrane oxygenation (ECMO) used as a
      RVAD established between a femoral vein and the pulmonary artery. Of the 44
      patients, 22 required addition of a temporary RVAD (t-RVAD group). Patients are
      sicker in the t-RVAD group with significantly higher rate of preoperative
      extracorporeal life support (46% vs. 9%; p = 0.016) or any mechanical circulatory
      support (55% vs. 14%; p = 0.01), more preoperative hemofiltration (23% vs. 0%; p
      = 0.048), and more inotrope support by dobutamine (68.2% vs. 27.3%; p = 0.015).
      Likewise Michigan risk score was significantly higher in t-RVAD group (2.61 +/-
      2.2 vs. 1.0 +/- 1.6 pts; p = 0.013) and INTERMACS clinical profile (2.1 +/- 0.6
      vs. 3.4 +/- 1.3 pts; p = 0.0001). Despite severity of preimplant conditions in t
      RVAD group, clinical outcomes did not differ in both groups with similar survival
      rate at 6 months (60.4 +/- 12 vs. 71.4 +/- 9.9%; p = 0.585). Early and liberal
      use of temporary RVAD in patients with risk factors of RVF could improve the
      prognostic after LVAD implantation.

PMID- 29210775
TI  - Isometric Exercise to Reduce Pain in Patellar Tendinopathy In-Season; Is It
      Effective "on the Road?"
AB  - OBJECTIVE: To investigate the effectiveness of an isometric squat exercise using
      a portable belt, on patellar tendon pain and function, in athletes during their
      competitive season. DESIGN: Case series with no requirements to change any aspect
      of games or training. The object of this pragmatic study was to investigate this
      intervention in addition to "usual management." A control or sham intervention
      was considered unacceptable to teams. SETTING: In-season. PARTICIPANTS: A total
      of 25 male and female elite and subelite athletes from 5 sports. INTERVENTION: 5
      * 30-second isometric quadriceps squat exercise using a rigid belt completed over
      a 4-week period. MAIN OUTCOME MEASURES: (1) single-leg decline squat (SLDS)-a
      pain provocation test for the patellar tendon (numerical rating score of pain
      between 0 and 10), (2) VISA-P questionnaire assessing patellar tendon pain and
      function, and (3) self-reported adherence with completing the exercise over a 4
      week period. RESULTS: Baseline SLDS pain was high for these in-season athletes,
      median 7.5/10 (range 3.5-9) and was significantly reduced over the 4-week
      intervention (P < 0.001, ES r = 0.580, median change 3.5). VISA-P scores improved
      after intervention (P < 0.001, ES r = 0.568, mean change 12.2 +/- 8.9, percentage
      mean change 18.8%, where minimum clinical important difference of relative change
      for VISA-P is 15.4%-27%). Adherence was high; athletes reported completing the
      exercise 5 times per week. CONCLUSIONS: This pragmatic study suggests that a
      portable isometric squat reduced pain in-season for athletes with PT. This form
      of treatment may be effective, but clinical trials with a control group are
      needed to confirm the results.

PMID- 29210776
TI  - Three experienced lactation consultants reflect upon the oral tie phenomenon.

PMID- 29210778
TI  - Psychoactive drugs and HIV: are we sure to treat our patients adequately?

PMID- 29210777
TI  - Costs and benefits of on-demand HIV preexposure prophylaxis in MSM.
AB  - OBJECTIVES: We undertook the economic evaluation of the double-blind randomized
      ANRS-IPERGAY trial, which showed the efficacy of on-demand preexposure
      prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC)
      in preventing HIV infection among high-risk MSM. DESIGN AND METHODS: The economic
      evaluation was prospective. Counseling, drugs (TDF-FTC at &OV0556;500.88 for 30
      tablets), tests, visits, and hospital admissions were valued based on in-trial
      use. The cost of on-demand PrEP/HIV infection averted was compared with the
      yearly and lifetime costs of HIV infection in France in a cost and benefits
      analysis. RESULTS: The yearly number of participants needed to treat to prevent
      one HIV infection was 17.6 (95% confidence interval = 10.7-49.9). The annual cost
      of counseling was &OV0556;690/participant. The total 1-year costs of PrEP were
      &OV0556;4271/participant, of which &OV0556;3129 (73%) were drug costs
      corresponding to 15 tablets of TDF-FTC/month. The yearly cost of on-demand PrEP
      to avoid one infection was &OV0556;75 258. Using TDF-FTC generic
      (&OV0556;179.9/30 tablets) reduced the 1-year costs of on-demand PrEP to
      &OV0556;2271/participant and &OV0556;39 970/infection averted, respectively.
      Using TDF-FTC at international market discounted prices (&OV0556;60/30 tablets)
      reduced the costs to &OV0556;1517/participant and the cost to &OV0556;26
      787/infection averted, comparable with the yearly treatment cost of HIV infection
      in France. On-demand PrEP was found to be cost saving in France if the duration
      of exposure was less than 7.5 years at current drug price and 13 years at generic
      price. CONCLUSION: On-demand PrEP in high-risk MSM with TDF-FTC can be considered
      cost saving. Other benefits include the treatments of other diseases and
      reductions in secondary infections.

PMID- 29210779
TI  - Remarkable plasma HIV RNA decrease by ombitasvir/paritaprevir/ritonavir in an HIV
      HCV coinfection case.

PMID- 29210780
TI  - Primary HIV infection in a Crohn's disease patient receiving infliximab
      maintenance therapy.

PMID- 29210785
TI  - Large Variability in the Diversity of Physiologically Complex Surgical Procedures
      Exists Nationwide Among All Hospitals Including Among Large Teaching Hospitals.
AB  - BACKGROUND: Multiple previous studies have shown that having a large diversity of
      procedures has a substantial impact on quality management of hospital surgical
      suites. At hospitals with substantial diversity, unless sophisticated statistical
      methods suitable for rare events are used, anesthesiologists working in surgical
      suites will have inaccurate predictions of surgical blood usage, case durations,
      cost accounting and price transparency, times remaining in late running cases,
      and use of intraoperative equipment. What is unknown is whether large diversity
      is a feature of only a few very unique set of hospitals nationwide (eg, the
      largest hospitals in each state or province). METHODS: The 2013 United States
      Nationwide Readmissions Database was used to study heterogeneity among 1981
      hospitals in their diversities of physiologically complex surgical procedures
      (ie, the procedure codes). The diversity of surgical procedures performed at each
      hospital was quantified using a summary measure, the number of different
      physiologically complex surgical procedures commonly performed at the hospital
      (ie, 1/Herfindahl). RESULTS: A total of 53.9% of all hospitals commonly performed
      <10 physiologically complex procedures (lower 99% confidence limit [CL], 51.3%).
      A total of 14.2% (lower 99% CL, 12.4%) of hospitals had >3-fold larger diversity
      (ie, >30 commonly performed physiologically complex procedures). Larger hospitals
      had greater diversity than the small- and medium-sized hospitals (P < .0001).
      Teaching hospitals had greater diversity than did the rural and urban nonteaching
      hospitals (P < .0001). A total of 80.0% of the 170 large teaching hospitals
      commonly performed >30 procedures (lower 99% CL, 71.9% of hospitals). However,
      there was considerable variability among the large teaching hospitals in their
      diversity (interquartile range of the numbers of commonly performed
      physiologically complex procedures = 19.3; lower 99% CL, 12.8 procedures).
      CONCLUSIONS: The diversity of procedures represents a substantive differentiator
      among hospitals. Thus, the usefulness of statistical methods for operating room
      management should be expected to be heterogeneous among hospitals. Our results
      also show that "large teaching hospital" alone is an insufficient description for
      accurate prediction of the extent to which a hospital sustains the operational
      and financial consequences of performing a wide diversity of surgical procedures.
      Future research can evaluate the extent to which hospitals with very large
      diversity are indispensable in their catchment area.

PMID- 29210786
TI  - Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake
      Inhibitors Are Not Associated With Bleeding or Transfusion in Cardiac Surgical
      Patients.
AB  - BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) and serotonin
      norepinephrine reuptake inhibitor (SNRI) use is known to alter platelet
      activation and aggregation leading to impairment in hemostasis. Previous studies
      are ambiguous with regard to bleeding, transfusion, and perioperative
      complications in patients undergoing cardiac surgery. The purpose of this study
      was to evaluate the risk of perioperative bleeding, transfusion, morbidity, and
      mortality in cardiac surgical patients taking SSRI/SNRIs compared with propensity
      matched controls. METHODS: Adult patients undergoing cardiac surgery with
      cardiopulmonary bypass at our institution between January 1, 2004, and December
      31, 2014, were eligible for study inclusion. Patients taking SSRI/SNRI
      medications at the time of surgery were identified and compared against all other
      patients not taking SSRI/SNRI medications to produce well-matched groups via
      propensity score analysis. Patients taking SSRI/SNRI medications were matched in
      a 1:1 ratio to control patients not taking these medications based on an
      internally estimated propensity score. Primary outcomes included perioperative
      blood transfusion, chest tube output, and reoperation for bleeding. Secondary
      outcomes included postoperative complications (renal failure, stroke or transient
      ischemic accident, prolonged mechanical ventilation, and perioperative myocardial
      infarction), intensive care unit (ICU) and hospital length of stay (LOS), and 30
      day mortality. RESULTS: A total of 1417 pairs of SSRI/SNRI patients and matched
      controls were retained for analysis. Between SSRI/SNRI patients and matched
      controls, there was no significant difference in postoperative chest tube output
      (median, 750.0 vs 750.0 mL; P = .860) or reoperation for bleeding (2.8% vs 2.5%;
      P = .892). Perioperative transfusion rates across all time points and blood
      product type were not significantly different between groups, with the overall
      perioperative transfusion rate for SSRI/SNRI patients 66.5% vs 64.9% for matched
      controls (P = .697). Patients in the SSRI/SNRI group had a higher rate of
      prolonged mechanical ventilation (13.1% vs 8.6%; P = .002), longer ICU LOS
      (median, 25.5 vs 23.8 hours; P < .001), and longer hospital LOS (median, 6.0 vs
      5.0 days; P < .001). Remaining mortality and outcome data were similar between
      groups. CONCLUSIONS: SSRI/SNRI use was not associated with an increased risk of
      bleeding or transfusion in patients undergoing cardiac surgery. While there was
      prolonged mechanical ventilation and increased ICU/hospital LOS in the SSRI/SNRI
      group, it is unclear that this finding is the result of such medications or
      rather associated with the underlying psychiatric condition for which they are
      prescribed. The results of this study suggest that perioperative interruption of
      SSRI/SNRIs to reduce the risk of perioperative bleeding and transfusion is
      unwarranted and may risk destabilization of patients' psychiatric condition.

PMID- 29210787
TI  - Nonhuman Primates in Anesthesia Research: Have We Reached the End of the Road?

PMID- 29210789
TI  - Predicting Severity of Acute Pain After Cesarean Delivery: A Narrative Review.
AB  - Cesarean delivery is one of the most common surgical procedures in the United
      States, with over 1.3 million performed annually. One-fifth of women who undergo
      cesarean delivery will experience severe pain in the acute postoperative period,
      increasing their risk of developing chronic pain and postpartum depression, and
      negatively impacting breastfeeding and newborn care. A growing body of research
      has investigated tools to predict which patients will experience more severe pain
      and have increased analgesic consumption after cesarean delivery. These include
      quantitative sensory testing, assessment of wound hyperalgesia, response to local
      anesthetic infiltration, and preoperative psychometric evaluations such as
      validated psychological questionnaires and simple screening tools. For this
      review, we searched MEDLINE, the Cochrane database, and Google Scholar to
      identify articles that evaluated the utility of various tools to predict severe
      pain and/or opioid consumption in the first 48 hours after cesarean delivery.
      Thirteen articles were included in the final review: 5 utilizing quantitative
      sensory testing, including patient responses to pressure, electrical, and thermal
      stimuli; 1 utilizing hyperalgesia testing; 1 using response to local anesthetic
      wound infiltration; 4 utilizing preoperative psychometric evaluations including
      the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, the Pittsburgh
      Sleep Quality Index, the Hospital Anxiety and Depression Scale, and simple
      questionnaires; and 2 utilizing a combination of quantitative sensory tests and
      psychometric evaluations. A number of modalities demonstrated statistically
      significant correlations with pain outcomes after cesarean delivery, but most
      correlations were weak to modest, and many modalities might not be clinically
      feasible. Response to local anesthetic infiltration and a tool using 3 simple
      questions enquiring about anxiety and anticipated pain and analgesic needs show
      potential for clinical use, but further studies are needed to evaluate the
      utility of these predictive tests in clinical practice.

PMID- 29210790
TI  - Management of 1-Lung Ventilation-Variation and Trends in Clinical Practice: A
      Report From the Multicenter Perioperative Outcomes Group.
AB  - BACKGROUND: Lung-protective ventilation (LPV) has been demonstrated to improve
      clinical outcomes in surgical patients. There are very limited data on the
      current use of LPV for patients undergoing 1-lung ventilation (1LV) despite
      evidence that 1LV may be a particularly important setting for its use. In this
      multicenter study, we report trends in ventilation practice for patients
      undergoing 1LV. METHODS: The Multicenter Perioperative Outcomes Group database
      was used to identify patients undergoing 1LV. We retrieved and calculated median
      initial and overall tidal volume (VT) for the cohort and for high-risk subgroups
      (female sex, obesity [body mass index >30 kg/m], and short stature), percentage
      of patients receiving positive end-expiratory pressure (PEEP) >=5 cm H2O, LPV
      during 1LV (VT <= 6 mL/kg predicted body weight [PBW] and PEEP >=5 cm H2O), and
      ventilator driving pressure (DeltaP; plateau airway pressure - PEEP). RESULTS:
      Data from 5609 patients across 4 institutions were included in the analysis.
      Median VT was calculated for each case and since the data were normally
      distributed, the mean is reported for the entire cohort and subgroups. Mean of
      median VT during 1LV for the cohort was 6.49 +/- 1.82 mL/kg PBW. VT (mL/kg PBW)
      for high-risk subgroups was significantly higher; 6.86 +/- 1.97 for body mass
      index >=30 kg/m, 7.05 +/- 1.92 for female patients, and 7.33 +/- 2.01 for short
      stature patients. Mean of the median VT declined significantly over the study
      period (from 6.88 to 5.72; P < .001), and the proportion of patients receiving
      LPV increased significantly over the study period (from 9.1% to 54.6%; P < .001).
      These changes coincided with a significant decrease in DeltaP during the study
      period, from 19.4 cm H2O during period 1 to 17.3 cm H2O in period 12 (P = .003).
      CONCLUSIONS: Despite a growing awareness of the importance of protective
      ventilation, a large proportion of patients undergoing 1LV continue to receive VT
      PEEP levels outside of recommended thresholds. Moreover, VT remains higher and
      LPV less common in high-risk subgroups, potentially placing them at elevated risk
      for iatrogenic lung injury.

PMID- 29210791
TI  - Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and
      Safety System.
AB  - BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of
      drug infusion rates according to measured clinical effect. The NeuroSENSE monitor
      provides an electroencephalographic measure of depth of hypnosis (wavelet-based
      anesthetic value for central nervous system monitoring [WAVCNS]). It has
      previously been used as feedback for closed-loop control of propofol, in a system
      designed using robust control engineering principles, which implements features
      specifically designed to ensure patient safety. Closed-loop control of a second
      drug, remifentanil, may be added to improve WAVCNS stability in the presence of
      variable surgical stimulation. The objective of this study was to design and
      evaluate the feasibility of a closed-loop system for robust control of propofol
      and remifentanil infusions using WAVCNS feedback, with an infusion safety system
      based on the known pharmacological characteristics of these 2 drugs. METHODS:
      With Health Canada authorization, research ethics board approval, and informed
      consent, American Society of Anesthesiologists I-III adults, requiring general
      anesthesia for elective surgery, were enrolled in a 2-phase study. In both
      phases, infusion of propofol was controlled in closed loop during induction and
      maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower
      estimated effect-site concentration limits. In phase I, remifentanil was
      administered using an adjustable target-controlled infusion and a controller was
      designed based on the collected data. In phase II, remifentanil was automatically
      titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for
      127 patients, of median (range) age 64 (22-86) years, undergoing surgical
      procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75
      in phase II. The overall control performance indicator, global score, was a
      median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in
      phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The
      WAVCNS was within +/-10 of the setpoint for 84.3% (76.6-90.6) of the maintenance
      of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference,
      3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was
      activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in
      phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved
      overall controller performance. This controller design offers a robust method to
      optimize the control of 2 drugs using a single sensor. The infusion safety system
      is an important component of a robust automated anesthesia system, but further
      research is required to determine the optimal constraints for these safe
      conditions.

PMID- 29210792
TI  - Technical Solutions and the Safety Big Picture.

PMID- 29210793
TI  - Failure of the Oxygen Gauge to Accurately Reflect the Pressure in the Oxygen
      Tank.

PMID- 29210794
TI  - Effect of Remote Ischemic Preconditioning on Outcomes in Adult Cardiac Surgery: A
      Systematic Review and Meta-analysis of Randomized Controlled Studies.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to
      prevent organ dysfunction in cardiac surgery patients. However, recent large,
      prospective, multicenter, randomized controlled trials (RCTs) had controversial
      results. Thus, a meta-analysis of RCTs was performed to investigate whether RIPC
      can reduce the incidence of acute myocardial infarction (AMI), acute kidney
      injury (AKI), and mortality in adult cardiac surgery patients. METHODS: Study
      data were collected from Medline, Elsevier, Cochrane Central Register of
      Controlled Trials and Web of Science databases. RCTs involving the effect of RIPC
      on organ protection in cardiac surgery patients, which reported the concentration
      or total release of creatine kinase-myocardial band, troponin I/troponin T
      (TNI/TNT) after operation, or the incidence of AMI, AKI, or mortality, were
      selected. Two reviewers independently extracted data using a standardized data
      extraction protocol where TNI or TNT concentrations; total TNI released after
      cardiac surgery; and the incidence of AKI, AMI, and mortality were recorded.
      Review Manager 5.3 software was used to analyze the data. RESULTS: Thirty trials,
      including 7036 patients were included in the analyses. RIPC significantly
      decreased the concentration of TNI/TNT (standard mean difference [SMD], -0.25
      ng/mL; 95% confidence interval [CI], -0.41 to -0.048 ng/mL; P = .004), creatine
      kinase-myocardial band (SMD, -0.22; 95% CI, -0.07-0.35 ng/mL; P = .46), and the
      total TNI/TNT release (SMD, -0.49 ng/mL; 95% CI, -0.93 to -0.55 ng/mL; P = .03)
      in cardiac surgery patients after a procedure. However, RIPC could not reduce the
      incidence of AMI (relative risk, 0.89; 95% CI, 0.70-1.13; P = .34) and AKI
      (relative risk, 0.88; 95% CI, 0.72-1.06; P = .18), and there was also no effect
      of RIPC on mortality in adult cardiac surgery patients. Interestingly, subgroup
      analysis showed that RIPC reduced incidence of AKI and mortality of cardiac
      surgery patients who received volatile agent anesthesia. CONCLUSIONS: Our meta
      analysis demonstrated that RIPC reduced TNI/TNT release after cardiac surgery.
      RIPC did not significantly reduce the incidence of AKI, AMI, and mortality.
      However, RIPC could reduce mortality in patients receiving volatile inhalational
      agent anesthesia.

PMID- 29210796
TI  - Perioperative Steroid Use for Tonsillectomy and Its Association With Reoperation
      for Posttonsillectomy Hemorrhage: A Retrospective Cohort Study.
AB  - BACKGROUND: Steroids reduce postoperative complications after tonsillectomy such
      as nausea and vomiting, pain, and delayed recovery. However, steroids may also
      increase the risk of severe posttonsillectomy bleeding requiring reoperation.
      METHODS: To evaluate the risk of postoperative bleeding requiring reoperation
      related to perioperative steroid use, we conducted a retrospective cohort study
      of 6149 patients treated at 68 hospitals using a hospital-based claims database.
      The primary outcome was reoperation for bleeding within 14 postoperative days. We
      estimated odds ratios (ORs) between perioperative steroid use and reoperation by
      multivariable logistic regression analysis adjusted for confounders. We also
      estimated differences in the adjusted risk. Subgroup analyses after dividing
      patients into adults and children were also performed. RESULTS: The incidence of
      reoperation did not differ significantly between patients who received steroids
      on the day of tonsillectomy and those who did not (1.8%, n = 15 vs 1.5%, n = 79;
      adjusted OR 0.81, 95% confidence interval [CI], 0.45-1.43; P = .46). We also
      found nonsignificant associations in both adults (OR, 0.73; 95% CI, 0.38-1.38; P
      = .33) and children (OR, 1.18; 95% CI, 0.34-4.11; P = .80). The adjusted risk
      differences estimated by the logistic regression model were -0.30% (95% CI, -1.05
      to 0.45) in all patients, -0.64% (95% CI, -1.82 to 0.54) in adults, and 0.13%
      (95% CI, -0.93 to 1.19) in children. CONCLUSIONS: Steroid use on the day of
      tonsillectomy was not associated with an increased risk of reoperation for
      bleeding. Although the wide range of CIs for the ORs could not eliminate the
      possibility of increased risk, especially in children, the incremental risks of
      reoperation for steroid use were within an acceptable range for both adults and
      children. Our results support the safety of perioperative steroid use for
      tonsillectomy, considering the magnitude of risk of reoperation because of
      bleeding.

PMID- 29210799
TI  - Extrauterine, Extragenital Endometrial Stromal Sarcoma in the Absence of
      Endometriosis: A Rare Entity.

PMID- 29210798
TI  - Investigation of 2 Prototypes of Novel Noncontact Technologies for Automated Real
      Time Capture of Incremental Drug Administration Data From Syringes.

PMID- 29210800
TI  - Molecular Modifiers of Hormone Receptor Action: Decreased Androgen Receptor
      Expression in Mismatch Repair Deficient Endometrial Endometrioid Adenocarcinoma.
AB  - Endometrial endometrioid carcinoma is related to estrogen excess and expression
      of estrogen and progesterone receptors. Epidemiological evidence suggests that
      exposure to elevated androgens, as in polycystic ovarian syndrome, increases the
      risk of endometrial cancer. Factors impacting androgen receptor (AR) expression
      are not well studied. Mismatch repair (MMR) deficiency due to MLH1 gene
      methylation is one of the most common molecular alterations in endometrial
      cancer, occurring in 15% to 20% of cases. MLH1 methylation can be associated with
      decreased expression of other genes, so we examined the effect of MMR status on
      AR expression. As NF-kappaB is known to induce AR, this transcription factor was
      also examined. Three hundred forty-four unselected endometrial carcinomas were
      evaluated for DNA MMR. Loss of expression of MLH1 with MLH1 methylation was
      defined as MMR deficient, and positive expression of MMR proteins was defined as
      MMR intact. A case-control cohort of 96 grade 2 endometrioid carcinomas was
      studied from this set (47 MMR deficient, 49 MMR intact). Cases were matched for
      histotype, grade, and age. AR and NF-kappaB immunohistochemical expression were
      evaluated by 2 different scoring systems (CAP/ASCO and Allred) used for estrogen
      receptor. Despite higher levels of NF-kappaB, MMR deficiency was associated with
      a significantly lower mean percentage of AR expression. The MMR deficient group
      had more variable AR expression, with more cases scoring on the lower end of the
      spectrum. These findings have implications for clinical trials of AR antagonists
      in gynecologic cancers.

PMID- 29210805
TI  - Development of a Simple Preoperative Risk Score for Persistent Pain After Breast
      Cancer Surgery: A Prospective Observational Cohort Study.
AB  - OBJECTIVES: Persistent postoperative pain is reported by 30% to 50% of patients
      following breast cancer surgery. Studies testing preventive measures, however,
      have so far failed to produce consistent positive results. If preventive measures
      could be targeted to a subgroup of patients at high risk of persistent pain,
      positive results would be more likely. Our aim was to develop a simple risk score
      predicting persistent pain after breast cancer surgery. MATERIALS AND METHODS: In
      a prospective observational cohort study, we tested the predictive ability of a 4
      simple items score for persistent pain in 200 patients scheduled for breast
      cancer surgery. A multivariable logistic regression model was created for the
      outcome of clinically important pain at 4 months. RESULTS: On the basis of
      literature review and univariable analysis of our data, 4 parameters were
      selected: preoperative pain at the surgical site, history of depression, age
      below 50 years and expected pain of high intensity (>6/10). Points for the score
      are based on the coefficients of the logistic regression model. A total score >=2
      points/5 predicts a risk of developing clinically important pain at 4 months
      >30%, with an area under the curve-receiver operating characteristic of 0.81.
      DISCUSSION: We studied known risk factors for persistent pain in patients
      scheduled for breast cancer surgery and constructed a preoperative risk score
      simple enough to select high-risk patients in future prevention studies.

PMID- 29210806
TI  - At the intersection of teaching and research: Mapping the health care management
      literature.

PMID- 29210807
TI  - Restoring Genital Hiatus to Normative Values After Apical Suspension Alone Versus
      With Level 3 Support Procedures.
AB  - OBJECTIVE: The aim of the study was to evaluate postoperative genital hiatus
      after apical suspension procedures without a level 3 support procedure (L3SP),
      posterior repair, and perineorrhaphy, compared with normative-value genital
      hiatus of 3.4 cm. METHODS: This an analysis of a pre-existing retrospectively
      collected database that included all minimally invasive sacrocolpopexies and
      uterosacral ligament suspensions performed at a tertiary medical center from
      January 2009 to August 2015. RESULTS: We identified 1006 surgical cases: 160
      (15.9%) apical suspensions with L3SPs and 846 (84.1%) without. Mean (SD) age was
      59 (9) years and body mass index was 27.6 (4.7) kg/m. Women were mainly white
      (97.4%) with stage III prolapse (67.8%). Those who underwent L3SPs were more
      likely to be premenopausal and undergo hysterectomy and USLS.Baseline genital
      hiatus was similar with and without L3SPs (4.8 [1.2] cm vs 4.6 [1.1] cm, P =
      0.096). Postoperative genital hiatus was reduced beyond normative (3.4 cm) after
      apical suspension without (3.0 [0.7] cm, P < 0.001) and with (2.8 [0.9] cm, P <
      0.001) L3SPs. Postoperative genital hiatus after L3SPs was similar to those
      without (2.8 [0.9] cm vs 3.0 [0.7] cm, P = 0.06). We found that change in genital
      hiatus was greater, by 0.7 cm, when L3SP was performed versus not performed (2.3
      [1.2] cm vs 1.6 [1.1] cm, P < 0.001). CONCLUSIONS: Level 3 support procedures may
      be unnecessary to restore genital hiatus to normal at time of apical suspension
      procedures and should be reserved for select patients.

PMID- 29210808
TI  - Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized
      Older Patients.
AB  - BACKGROUND: Treatment with antipsychotic drugs has been associated with glucose
      dysregulation in older outpatients, especially in the early stage of therapy. The
      underlying mechanism is, however, unclear. The aim of this study was to
      investigate changes in glucose levels during haloperidol use compared with the
      use of placebo among older hospitalized patients. METHODS: This substudy was part
      of a larger multicenter, randomized, double blind, placebo-controlled clinical
      trial among hospitalized patients aged 70 years and older who had an increased
      risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch
      Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to
      participate in the study. Participating patients were randomized for treatment
      and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7
      consecutive days (14 doses). Exclusion criteria for this substudy were the use of
      corticosteroids and changes in diabetes medication. Random blood samples to
      determine glucose levels were collected before day 1 and on day 6 of the study.
      Student independent sample t test was used to determine differences in glucose
      changes between both groups. RESULTS: Twenty-nine patients were included
      (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users
      was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the
      mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and
      150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant
      (P = 0.685). CONCLUSIONS: Short-term prophylactic use of haloperidol was not
      associated with changes in glucose levels in older hospitalized patients compared
      with those given a placebo in this small study.

PMID- 29210809
TI  - Evaluation and refinement of a handheld health information technology tool to
      support the timely update of bedside visual cues to prevent falls in hospitals.
AB  - AIM: To evaluate clinicians' perspectives, before and after clinical
      implementation (i.e. trial) of a handheld health information technology (HIT)
      tool, incorporating an iPad device and automatically generated visual cues for
      bedside display, for falls risk assessment and prevention in hospital. METHODS:
      This pilot study utilized mixed-methods research with focus group discussions and
      Likert-scale surveys to elicit clinicians' attitudes. The study was conducted
      across three phases within two medical wards of the Queen Elizabeth Hospital.
      Phase 1 (pretrial) involved focus group discussion (five staff) and surveys (48
      staff) to elicit preliminary perspectives on tool use, benefits and barriers to
      use and recommendations for improvement. Phase 2 (tool trial) involved HIT tool
      implementation on two hospital wards over consecutive 12-week periods. Phase 3
      (post-trial) involved focus group discussion (five staff) and surveys (29 staff)
      following tool implementation, with similar themes as in Phase 1. Qualitative
      data were evaluated using content analysis, and quantitative data using
      descriptive statistics and logistic regression analysis, with subgroup analyses
      on user status (P <= 0.05). RESULTS: Four findings emerged on clinicians'
      experience, positive perceptions, negative perceptions and recommendations for
      improvement of the tool. Pretrial, clinicians were familiar with using visual
      cues in hospital falls prevention. They identified potential benefits of the HIT
      tool in obtaining timely, useful falls risk assessment to improve patient care.
      During the trial, the wards differed in methods of tool implementation, resulting
      in lower uptake by clinicians on the subacute ward. Post-trial, clinicians
      remained supportive for incorporating the tool into clinical practice; however,
      there were issues with usability and lack of time for tool use. Staff who had not
      used the tool had less appreciation for it improving their understanding of
      patients' falls risk factors (odds ratio 0.12), or effectively preventing
      hospital falls (odds ratio 0.12). Clinicians' recommendations resulted in
      subsequent technological refinement of the tool, and provision of an additional
      iPad device for more efficient use. CONCLUSION: This study adds to the limited
      pool of knowledge about clinicians' attitudes toward health technology use in
      falls avoidance. Clinicians were willing to use the HIT tool, and their concerns
      about its usability were addressed in ongoing tool improvement. Including end
      users in the development and refinement processes, as well as having high staff
      uptake of new technologies, is important in improving their acceptance and usage,
      and in maximizing beneficial feedback to further inform tool development.

PMID- 29210811
TI  - HOW QUICKLY THINGS CHANGE: UPDATES IN PUBLISHING THAT AFFECT YOU.

PMID- 29210810
TI  - Restoring Perceived Loudness for Listeners With Hearing Loss.
AB  - OBJECTIVES: Normalizing perceived loudness is an important rationale for gain
      adjustments in hearing aids. It has been demonstrated that gains required for
      restoring normal loudness perception for monaural narrowband signals can lead to
      higher-than-normal loudness in listeners with hearing loss, particularly for
      binaural broadband presentation. The present study presents a binaural bandwidth
      adaptive dynamic compressor (BBDC) that can apply different gains for narrow- and
      broadband signals. It was hypothesized that normal perceived loudness for a broad
      variety of signals could be restored for listeners with mild to moderate high
      frequency hearing loss by applying individual signal-dependent gain corrections.
      DESIGN: Gains to normalize perceived loudness for narrowband stimuli were
      assessed in 15 listeners with mild to moderate high-frequency hearing loss using
      categorical loudness scaling. Gains for narrowband loudness compensation were
      calculated and applied in a standard compressor. Aided loudness functions for
      signals with different bandwidths were assessed. The deviation from the average
      normal-hearing loudness functions was used for gain correction in the BBDC. Aided
      loudness functions for narrow- and broadband signals with BBDC were then
      assessed. Gains for a 65 dB SPL speech-shaped noise of BBDC were compared with
      gains based on National Acoustic Laboratories' nonlinear fitting procedure
      version 2 (NAL-NL2). The perceived loudness for 20 real signals was compared to
      the average normal-hearing rating. RESULTS: The suggested BBDC showed close-to
      normal loudness functions for binaural narrow- and broadband signals for the
      listeners with hearing loss. Normal loudness ratings were observed for the real
      world test signals. The proposed gain reduction method resulted on average in
      similar gains as prescribed by NAL-NL2. However, substantial gain variations
      compared to NAL-NL2 were observed in the data for individual listeners. Gain
      corrections after narrowband loudness compensation showed large interindividual
      differences for binaural broadband signals. Some listeners required no further
      gain reduction for broadband signals; for others, gains in decibels were more
      than halved for binaural broadband signals. CONCLUSION: The interindividual
      differences of the binaural broadband gain corrections indicate that relevant
      information for normalizing perceived loudness of binaural broadband signals
      cannot be inferred from monaural narrowband loudness functions. Over
      amplification can be avoided if binaural broadband measurements are included in
      the fitting procedure. For listeners with a high binaural broadband gain
      correction factor, loudness compensation for narrowband and broadband stimuli
      cannot be achieved by compression algorithms that disregard the bandwidth of the
      input signals. The suggested BBDC includes individual binaural broadband
      corrections in a more appropriate way than threshold-based procedures.

PMID- 29210813
TI  - Effect of Low-Volume Split-Dose Purgative on the Quality of Bowel Prep for
      Colonoscopy on the Hospitalized Patient.
AB  - Although colon cancer is preventable, it is still the second leading cause of
      cancer death in both men and women in the United States (). Colonoscopy is as yet
      the gold standard for colon cancer prevention (). The success of colonoscopy is
      dependent upon the quality of the bowel prep. The problem addressed in this study
      was the impact of hospitalization on bowel prep quality. The participants in this
      study were 54 consecutive inpatients older than 18 years and 52 consecutive
      outpatients older than 18 years who were scheduled for colonoscopy in the
      Endoscopy Lab at Santa Barbara Cottage Hospital. Convenience sampling was used to
      collect sample data utilizing the Boston Bowel Prep Scale (BBPS). The study group
      contained 48.1% of the inpatients who had a BBPS of less than seven (out of nine
      total possible points with a score of nine representing the most optimal prep
      outcome) compared to 19.2% of the outpatients. Efforts to improve bowel prep
      palatability, decrease cost, and decrease side effects while improving quality
      should be continued. Split-dosing is a best practice recommendation. This
      researcher hypothesized that an intervention in the form of a lower-volume, split
      dosage prep would improve the quality of bowel prep in the inpatient population.
      There was a statistically significant improvement noted with the intervention
      group in the follow-up study, which indicates potential for improving the quality
      of bowel prep for screening colonoscopy, thus a possibility for better colon
      health surveillance.

PMID- 29210814
TI  - Caregiver Education Reduces the Incidence of Community-Acquired CLABSIs in the
      Pediatric Patient With Intestinal Failure.
AB  - Pediatric patients with intestinal failure often require central venous catheters
      for extended periods of time for parenteral nutrition, blood sampling, and
      medication administration, increasing morbidity, mortality, and costs. In 2007,
      we reported a central line-associated bloodstream infection rate of 7.0 per 1,000
      catheter line-days in our pediatric patients with intestinal failure. On the
      basis of this high rate of catheter-associated infections, we developed and
      implemented a central line care curriculum for patients/family caregivers and
      home health nurses. We aim to show with the implementation of patient/family
      caregiver and home health nurse standardized education, the central line
      associated bloodstream infection rate can be significantly reduced and that this
      is sustainable. A retrospective review of 80 pediatric outpatients with
      intestinal failure and long-term central venous access was performed between
      January 1, 2009, and December 31, 2014. During this time period, the nursing
      department at Children's Medical Center of Dallas implemented a systematic
      central line care education program for patients and/or caregivers. The number of
      community-acquired central line-associated bloodstream infections during this
      time period was collected and compared with our previously reported data from
      2005 to 2007 prior to the implementation of education program. With the
      implementation of standardized care guidelines and a central venous catheter care
      curriculum, the community-acquired rate decreased from 4.8 to 2.9 per 1,000
      catheter-days in 80 patients with intestinal failure between January 1, 2009, and
      December 31, 2014 (p < .001). This was also a significant decrease compared with
      the initial central line-associated bloodstream infection rate of 7.0 per 1,000
      central line days in 2007 (p < .001) prior to the development of the central
      venous catheter care curriculum. We have shown that the incidence of community
      acquired central line-associated bloodstream infections in children with
      intestinal failure can be reduced through formal education of central venous
      catheter care to family members.

PMID- 29210815
TI  - Effect of Home Care Nursing on Patients Discharged From Hospital With Self
      Reported Signs of Constipation: A Randomized Trial.
AB  - Constipation is a common health problem in relation to hospitalization. This
      randomized controlled trial aimed to investigate whether advice from a home care
      nurse after discharge had an effect on self-reported signs of constipation. A
      total of 59 patients were included in the study on the basis of their self
      reported signs of constipation evaluated using the Constipation Assessment Scale.
      Advice from the home care nurses was given on the intake of fiber and liquid and
      mobilization related to scorings on the Constipation Risk Assessment Scale, the
      administration of laxatives, and referral to a physician when needed. Results
      showed a tendency toward the visits being effective, but a more complex
      intervention might be needed.

PMID- 29210816
TI  - Nursing Assessment of Patients Requiring Enteral and Gastric Feeding Tubes: An
      Exploratory Approach.
AB  - There is insufficient information available in the current literature regarding
      how nurses assess, intervene, and advocate for patients with indwelling gastric
      and enteral tube feedings. To understand ways in which nurses could be more
      supportive, a survey, distributed through private online social media groups, was
      designed to elicit preliminary data from patients who are currently, or had
      recently been treated, with a feeding tube. This survey examines nurse behaviors
      that patients identify as actually or potentially helpful with the physical,
      emotional, social, and logistical aspects of having a feeding tube. The results
      of the survey reveal that, although some patients report feeling cared for by
      nurses and believe that their nurses were compassionate, a greater number of
      respondents express that their nurses were less informed and less able to provide
      help with their emotional challenges. Further investigation is needed to assess
      how nurses can better support these patients and better identify the successful
      and transformative interventions that would be helpful to them.

PMID- 29210817
TI  - Influence of Different Lengths of Rubber Tube on Patients After Esophageal Stent
      Implantation Using a Silk Thread.
AB  - Our objective was to compare the efficacy of different lengths of rubber tube (6
      French) on patients with esophageal stent implantation performed using a silk
      thread. We measured the effects in terms of pain and foreign body sensation felt
      in the pharynx and esophageal mucosa of the patients. A retrospective analysis
      was conducted using records of 65 patients who were divided into 3 groups. Group
      A had 20 cases with the distal end of the tube toward the nasal cavity, Group B
      had 21 cases with the distal end of the tube reaching the nasopharynx without
      exceeding the soft palate, and Group C had 24 cases with the distal end of the
      tube toward the upper end of the stent. Follow-up was performed on 1 day, 2 days,
      1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks postoperatively. During each
      period, the pain scores for Groups B and C were lower than those for Group A (p <
      .05), whereas no difference was observed when Groups B and C were compared.
      Although no variations were seen between the 3 groups in terms of the proportion
      of patients with foreign body sensation on the first day (p > .05), Groups A and
      B had a lower proportion than Group C (p < .05) at those periods. No difference
      was observed when Groups A and B were compared. In conclusion, the Group B method
      was successful in alleviating the side effects caused by the silk thread.

PMID- 29210818
TI  - Evaluation of Adherence to American Society of Health-System Pharmacists
      Guidelines: Stress Ulcer Prophylaxis in Shiraz, Iran.
AB  - Overuse of stress ulcer prophylaxis has a considerable cost burden on patient and
      healthcare systems. This study aimed to determine the adherence level of stress
      ulcer prophylaxis use with American Society of Health-System Pharmacists
      guidelines in a teaching hospital in Shiraz, Iran. From March to September 2013,
      we enrolled all eligible patients admitted to the general medical wards of Shahid
      Faghihi Hospital, Shiraz, Iran. According to American Society of Health-System
      Pharmacists guidelines, patients who had at least one major or two minor risk
      factors for stress ulcers and received stress ulcer prophylaxis were labeled as
      adherent, others were considered nonadherent. During the study period, 441
      patients enrolled, of which 257 (58.3%) were women. The mean +/-SD age of
      patients was 54.7 +/- 20 years. The mean +/-SD length of hospital stay for
      patients was 11.3 +/- 6 days. Overall, 354 patients (80.2%) received proton pump
      inhibitors as stress ulcer prophylaxis. There were 127 patients who properly
      received stress ulcer prophylaxis. Total adherence to American Society of Health
      System Pharmacists guidelines in our hospital was 28.8%. We observed a high
      frequency of unnecessary use of stress ulcer prophylaxis in hospitalized,
      noncritically ill patients with inappropriate continuation after discharge.

PMID- 29210819
TI  - CHYLOUS ASCITES AFTER LAPAROSCOPIC LOW ANTERIOR COLORECTAL RESECTION FOR
      RECTOSIGMOID CARCINOMA: A CASE REPORT AND A LITERATURE REVIEW.

PMID- 29210820
TI  - LONG-TERM PROTON PUMP INHIBITOR (PPI) USE AND THE DEVELOPMENT OF GASTRIC
      PREMALIGNANT LESIONS.

PMID- 29210821
TI  - MOMENTS THAT TAKE YOUR BREATH AWAY.

PMID- 29210823
TI  - PERIPHERALLY ACTING MU-OPIOID RECEPTOR ANTAGONISTS.

PMID- 29210822
TI  - PERIPHERALLY ACTING MU-OPIOID RECEPTOR ANTAGONISTS.

PMID- 29210825
TI  - Graftless Maxillary Sinus Lift Using Lateral Window Approach: A Systematic
      Review.
AB  - PURPOSE: The aim was to determine the survival rate of dental implants installed
      in the posterior region of the maxilla after a graftless maxillary sinus lift via
      the lateral window approach and to identify the factors involved in the results.
      MATERIALS AND METHODS: A systematic search was done on MEDLINE, EMBASE, LILACS,
      Scopus, and Science Direct up to June 2016; additional studies were identified
      through an analysis of references. Primary studies in English, Spanish,
      Portuguese, and French were included; the selection and data extraction process
      was conducted by 2 investigators independently, and the methodological quality
      was evaluated by means of the Effective Public Health Practice Project's Quality
      Assessment Tool. RESULTS: The combined search identified 232 articles. After the
      selection process, 11 articles were identified, 9 of which were prospective and 2
      were retrospective. In all of them, the graftless maxillary sinus lift was done
      with the immediate installation of the implant. All the studies included
      presented a low methodological quality. The mean survival rate of the implants
      was 97% with an average new intrasinus bone formation of 6.2 mm. CONCLUSION: This
      technique has a high implant survival although it is not possible to identify its
      correct indication and contraindication.

PMID- 29210827
TI  - Demarcation Line in the Human Cornea After Surface Ablation Observed by Optical
      Coherence Tomography and Confocal Microscopy.
AB  - PURPOSE: To investigate the long-term changes in anterior corneal structure after
      surface ablation. METHODS: In this retrospective study, patients who received
      surface ablation including laser-assisted subepithelial keratomileusis (LASEK)
      and epipolis laser in situ keratomileusis at the Department of Ophthalmology of
      Fudan University Eye and Ear, Nose and Throat (EENT) Hospital (Shanghai, People's
      Republic of China) were telephoned. Patients were asked to follow-up at the
      refractive center. Changes in the anterior cornea (from the epithelium to the
      anterior stroma) were examined by optical coherence tomography (OCT) and in vivo
      confocal microscopy. RESULTS: Thirty-four eyes of 18 patients (10 years or more
      after operation), 16 eyes of 8 patients (4 years after operation), 12 eyes of 6
      patients (1 year after operation), 8 eyes of 4 patients (6 months after
      operation), and 12 eyes of 6 patients (1 month after operation) were included.
      Under OCT, a smooth, continuous, and highly reflective demarcation line between
      the epithelial layer and the stroma was noted in all eyes that received surgeries
      more than 1 year previously. For eyes at 6 months after operation, the complete
      formation of this demarcation line was detected in 12.5% (1/8) of eyes and a
      partial formation of this demarcation line was observed in 87.5% (7/8) of eyes. A
      partial formation of this demarcation line was observed in 100% (12/12) of eyes
      in patients at 1 month after surgery. CONCLUSIONS: A demarcation line in the
      human cornea can be detected after corneal surface ablation. It was completely
      formed around postoperative 6 to 12 months. The functions and components of this
      structure merit investigation.

PMID- 29210826
TI  - High Acceptability and Increased HIV-Testing Frequency After Introduction of HIV
      Self-Testing and Network Distribution Among South African MSM.
AB  - BACKGROUND: South African men who have sex with men (MSM) have a high burden of
      undiagnosed HIV infection and HIV-testing rates incommensurate with their risk.
      HIV self-testing (HIVST) may increase testing uptake, frequency, and earlier HIV
      detection and treatment. SETTING: Gert Sibande and Ehlanzeni districts,
      Mpumalanga Province, South Africa. METHODS: We conducted a longitudinal HIVST
      study among MSM between June 2015 and May 2017. Overall 127 HIV-negative MSM were
      provided with up to 9 test kits of their choice-oral fluid or blood fingerstick
      to use themselves and distribute to their networks. Surveys conducted 3- and 6
      month post-enrollment elicited information on HIVST experiences, preferences,
      acceptability, utilization, and distribution. We used generalized estimating
      equations to assess changes in testing frequency. RESULTS: Ninety-one percent of
      participants self-tested. All participants who self-tested reported being likely
      to self-test again, with over 80% preferring HIVST to clinic-based testing.
      Fingerstick was preferred to oral fluid tests by approximately 2:1. Returning
      participants distributed 728 tests to sexual partners (18.5% of kits), friends
      (51.6%), and family (29.8%). Six participants seroconverted during the study, and
      40 new diagnoses were reported among test recipients. Frequent (semi-annual)
      testing increased from 37.8% before the study to 84.5% at follow-up (P < 0.001),
      and participants reported anticipated frequent testing of 100% if HIVST were
      available compared with 84% if only clinic-testing were available in the coming
      year (P < 0.01). CONCLUSIONS: HIVST use and network distribution is acceptable
      and feasible for MSM in South Africa and can increase testing uptake and
      frequency, potentially improving early detection among MSM and their networks.

PMID- 29210828
TI  - Predicting Short-Term Subjective Vision Performance of Contact Lenses Used in
      Myopia Control.
AB  - OBJECTIVE: To investigate whether initial assessment of contact lenses prescribed
      for myopia control (MC) predicts short-term visual performance. METHOD:
      Retrospective analysis of 43 participants in a double-masked, randomized, cross
      over trial wearing at least one lens: single-vision (SV) lens (1-DAY ACUVUE
      MOIST) or MC lenses (MiSight or Proclear Multifocal-Distance +2.00D).
      Participants completed questionnaires at the fitting visit, a take-home
      questionnaire (THQ) 3 days after fitting and finally at the assessment visit (>=5
      days after fitting). Questions comprised vision clarity and lack of ghosting
      (distance, intermediate, near at day/night time); vision stability; driving
      vision; overall vision satisfaction and comfort (1-10 scale, 1-point steps); and
      willingness to purchase based on vision and MC benefit of lens (yes/no response).
      Visual acuity was measured at fitting and assessment visits. RESULTS: Vision
      clarity (intermediate and near) was significantly worse at assessment compared
      with fitting while wearing MC lenses (P<0.001), as was overall vision
      satisfaction (P<0.001), comfort (P<0.001), and vision stability (P=0.001) while
      wearing either SV or MC lenses. Participants willing to purchase at assessment
      visit was 84% with SV and 36% with MC lenses, increasing to 88% (SV, P=1.00) and
      61% (MC, P<0.001) if the lenses slowed myopia progression. Visual acuity was no
      different with either MC or SV lenses at fitting or assessment (P>=0.251).
      CONCLUSION: Initial performance at fitting did not predict short-term performance
      for SV or MC lenses. A significant increase in willingness to purchase if lenses
      slowed myopia progression was observed while wearing MC lenses. Educating
      patients on the benefits might increase acceptability of MC lenses.

PMID- 29210829
TI  - In Vitro Evaluation of Adhesion of Two Acanthamoeba Strains to Cosmetic Contact
      Lenses.
AB  - PURPOSE: To evaluate the factors affecting the adhesion of Acanthamoeba
      trophozoites to the surface of cosmetic contact lenses (CCLs). METHODS:
      Acanthamoeba castellanii and A. hatchetti trophozoites were inoculated onto CCLs
      (hema copolymer [HM] [38.5% H2O], phemfilcon [PF] [55% H2O], polymacon [PM] [38%
      H2O], polyhema [PH] [%42 H2O], and hema [HM55] [55% H2O]), and the number of
      trophozoites adhered to the lens surfaces was assessed over time, that is, at 15
      min, 1, and 24 hr. In addition, scanning electron microscopy (SEM) analysis of
      the lens surfaces was performed to evaluate the effect of lens surface topology
      on adhesion. RESULTS: The number of amoeba adhered to the contact lens surface
      was found lower with PF and PH production materials, than lenses with HM, PM, and
      HM55 production materials (P<0.05). No significant difference was detected in
      amoebic strains adhered in all the contact lens types (P>0.05). No significant
      difference was found on average amoeba adhesion between contact lenses with hema
      production material but with different water contents (45%, 55%), to see the
      effect of water content on amoebic adhesion (P>0.05). As a result of SEM
      analysis, surface topology showed no effect on adhesion. CONCLUSION: (1) Chemical
      composition of lenses seemed to be mostly responsible for the adhesion of
      Acanthamoeba. (2) Different numbers of trophozoites, obtained after the adhesion
      experiment, could also indicate that adherence capacity can also differ among
      Acanthamoeba species.

PMID- 29210830
TI  - Brief Report: Tenofovir-Associated Nephrotoxicity Among a US National Historical
      Cohort of HIV-Infected Veterans: Risk Modification by Concomitant
      Antiretrovirals.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with renal
      complications. The third agent in TDF-containing antiretroviral regimens may
      modify that risk. We compared renal adverse outcomes among treatment-naive HIV
      infected patients initiating TDF-containing regimens including efavirenz (EFV) or
      other agents. SETTING: This population-based historical cohort study used
      national Veterans Health Administration (VHA) clinical and administrative data
      sets to identify treatment-naive HIV-infected veterans initiating antiretroviral
      therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV),
      elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors
      (PIs) from 2003 to 2015. METHODS: Unadjusted incidence rates (IRs) for each
      regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards
      models and inverse probability of treatment weighting] for between-regimen
      comparisons were calculated for renal outcomes including confirmed proteinuria,
      defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to
      creatinine ratios >30 mg/g occurring >=90 days apart; chronic kidney disease
      (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements
      <60 mL.min.1.73 m occurring >=90 days apart; and kidney dialysis. RESULTS: Of
      33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173
      RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD
      IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis
      IRs were rare and comparable). After inverse probability of treatment weighting
      adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV +
      TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72),
      EVG/c/TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV
      boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). CONCLUSIONS: EFV + TDF/FTC was
      associated with significantly lower risk of CKD versus other TDF-containing
      regimens in the Veterans Health Administration.

PMID- 29210832
TI  - Quality of Caregiving is Positively Associated With Neurodevelopment During the
      First Year of Life Among HIV-Exposed Uninfected Children in Uganda.
AB  - OBJECTIVE: We sought to evaluate whether maternal characteristics and infant
      developmental milieu were predictive of early cognitive development in HIV
      exposed uninfected (HEU) and HIV-unexposed uninfected (HU) infants in Uganda.
      DESIGN: Longitudinal pregnancy study. METHODS: Ugandan women (n = 228) were
      enrolled into the Postnatal Nutrition and Psychosocial Health Outcomes study with
      a 2:1 HIV-uninfected: infected ratio. Maternal sociodemographic, perceived social
      support, and depressive symptomatology were assessed. Infant growth and
      neurocognitive development were assessed at 6 and 12 months of age using Mullen
      Scales of Early Learning (MSEL). Caldwell Home Observation for Home Environment
      was used to gauge caregiving quality. Linear mixed-effects models were built to
      examine the relationships between maternal and infant characteristics with infant
      MSEL scores by HIV exposure. RESULTS: Two MSEL measures were available for 215
      mother-child dyads: 140 infants (65%) were HIV-uninfected (HU), 57 (27%) were HIV
      exposed uninfected (HEU) with mothers reporting antiretroviral therapy, and 18
      (8%) were HEU with mothers not reporting antiretroviral therapy. HEU had lower
      MSEL Composite (beta = -3.94, P = 0.03) and Gross Motor scores (beta = -3.41, P =
      0.01) than HU. Home Observation for Home Environment total score was positively
      associated with MSEL Composite (beta = 0.81, P = 0.01), Receptive Language (beta
      = 0.59, P = 0.001), and Expressive Language (beta = 0.64, P = 0.01) scores.
      CONCLUSIONS: HIV exposure is associated with lower infant cognitive development
      scores. Increasing maternal quality of caregiving may improve early cognitive
      development.

PMID- 29210833
TI  - Influence of Injection Drug Use-Related HIV Acquisition on CD4 Response to First
      Antiretroviral Therapy Regimen Among Virally Suppressed Individuals.
AB  - BACKGROUND: The inflammatory effects of injection drug use (IDU) may result in an
      impaired immune response to antiretroviral therapy (ART). We examined CD4
      response to first ART regimen among individuals in routine HIV care, stratified
      by IDU-related HIV acquisition. SETTING: Cohort study including patients who
      initiated ART between 2000 and 2015 in the Johns Hopkins HIV Clinic. METHODS: We
      followed individuals from ART initiation until death, loss to follow-up, loss of
      viral load suppression (<500 copies/mL), or administrative censoring. We
      described CD4 trajectories after ART initiation using inverse probability
      weighted quantile regression models with restricted cubic splines for time.
      Weights accounted for differences in baseline characteristics of persons
      comparing those with IDU-related HIV acquisition to those with other HIV
      acquisition risks (non-IDU) and possible nondifferential censoring due to death,
      loss to follow-up, or loss of viral load suppression. We also examined CD4
      response by strata of CD4 at ART initiation (<=200, 201-350, >350). RESULTS: Of
      1244 patients initiating ART, 30.4% were IDU. Absolute CD4 cell difference at the
      50th percentile comparing IDU with non-IDU was -25 cells [95% confidence interval
      (CI): -63 to 35], -66 cells (95% CI: -141 to 16), and -91 cells (95% CI: -190 to 
      5) at 2, 4, and 6 years after ART initiation, respectively. Results were similar
      (non-IDU with slightly higher CD4 count, but not statistically significant
      differences) at other percentiles and stratified by baseline CD4. CONCLUSIONS:
      CD4 recovery after ART initiation was similar for IDU and non-IDU, conditional on
      consistent viral load suppression.

PMID- 29210834
TI  - Pre-Exposure Prophylaxis (PrEP) Use and Condomless Anal Sex: Evidence of Risk
      Compensation in a Cohort of Young Men Who Have Sex with Men.
AB  - BACKGROUND: Young men who have sex with men (YMSM) are disproportionately
      impacted by HIV. Pre-exposure prophylaxis (PrEP) is highly effective at
      preventing HIV acquisition. It remains unclear if PrEP use increases rates of
      condomless sex (ie, risk compensation), which may increase risk of infection if
      PrEP adherence is not optimal. This study aimed to examine whether PrEP use and
      PrEP adherence were associated with change in sexual risk behaviors in a large
      longitudinal cohort of YMSM reporting on multiple sexual partnerships over time.
      METHOD: Data were obtained from the first 3 visits of an ongoing cohort study of
      YMSM in Chicago (analytic N = 953; 14.1% HIV-positive at baseline). Participants
      reported up to 4 sexual partnerships at each visit, including sexual behavior,
      PrEP use, and PrEP adherence within partnerships. RESULTS: YMSM reported higher
      rates of receptive condomless anal sex (CAS) in partnerships during which they
      were on PrEP compared with those when they were not on PrEP. This association was
      consistent across both HIV-negative and HIV-positive participants reporting on
      partnerships with both perceived HIV-negative/unknown and HIV-positive partners.
      The rate of receptive CAS was higher in PrEP nonadherent partnerships compared
      with non-PrEP partnerships. The rate of receptive CAS was also higher in PrEP
      nonadherent than adherent partnerships, but this was not statistically
      significant. CONCLUSIONS: These analyses provide compelling data suggesting that
      YMSM are engaging in risk compensation when on PrEP. If rates of receptive CAS
      are highest among YMSM who are PrEP nonadherent, PrEP as a prevention strategy
      could fail to curb HIV incidence among YMSM.

PMID- 29210835
TI  - Medication Adherence in a Nationwide Cohort of Veterans Initiating Pre-exposure
      Prophylaxis (PrEP) to Prevent HIV Infection.
AB  - BACKGROUND: Current guidelines for pre-exposure prophylaxis (PrEP) to prevent HIV
      infection call for long-term, daily use of tenofovir disoproxil
      fumarate/emtricitabine (TDF/FTC). Little is known about long-term adherence with
      TDF/FTC prescribed for PrEP in routine clinical practice. SETTING: Veterans
      Health Administration (VHA) clinics. METHODS: We used VHA data to create a
      nationwide cohort of Veterans initiating PrEP between July 1, 2012, and June 30,
      2016. We examined pharmacy refill data to estimate adherence based on the
      proportion of days covered (PDC) by TDF/FTC in the first year and used logistic
      regression to identify patient characteristics associated with high adherence
      (ie, PDC >0.8). We also quantified how often Veterans discontinued PrEP in the
      first year, based on a gap of 120 days or more in medication possession. RESULTS:
      Among 1086 individuals initiating PrEP, the median PDC for TDF/FTC in the first
      year was 0.74 (interquartile range 0.40-0.92). In multivariable analysis, high
      adherence was associated with older age (odds ratio 1.97; 1.41-2.74 for age 50-64
      compared with <35), white compared with black race (odds ratio 2.12; 1.53-2.93),
      and male sex (odds ratio 3.39; 1.37-8.42). Forty-four percent discontinued PrEP
      in the first year. CONCLUSIONS: First-year adherence with TDF/FTC was overall
      high in a nationwide cohort of PrEP users. Differences in adherence by age, race,
      and sex suggest potential for disparities in PrEP effectiveness in routine
      clinical practice.

PMID- 29210840
TI  - Conoscere e Curare il Cuore 1986-2016: how the heart has changed.

PMID- 29210839
TI  - Cataract surgery in ocular surface diseases: clinical challenges and outcomes.
AB  - PURPOSE OF REVIEW: Cataracts are a significant cause of blindness and visual
      impairment worldwide. With the recent advances in cataract surgery techniques,
      outcomes have improved significantly in uncomplicated cases. This article
      discusses the challenges and outcomes of cataract surgery in complex cases
      targeting eyes with ocular surface diseases like Stevens-Johnson syndrome, ocular
      cicatricial pemphigoid, Mooren's ulcer, vernal keratoconjunctivitis and limbal
      stem cell deficiency. RECENT FINDINGS: Ocular surface diseases are commonly
      associated with corneal scarring and vascularization, conjunctival inflammation,
      symblepharon and forniceal shortening. Any surgical intervention in a hostile
      ocular surface environment may worsen the disease, which may result in visual
      deterioration. In recent past, with the use of immunosuppressants and with the
      introduction of different ocular surface reconstruction surgeries; stabilization
      of ocular surface can be achieved prior to planning cataract surgery. This kind
      of step-wise approach can considerably improve visual outcomes in such cases.
      SUMMARY: Cataract surgery in ocular surface diseases needs careful preoperative,
      intraoperative and postoperative planning. Performed in a staged manner under
      favorable ocular environment, it has good visual outcomes and can improve the
      quality of life in such patients.

PMID- 29210836
TI  - Abdominal Fat Depots and Subclinical Carotid Artery Atherosclerosis in Women With
      and Without HIV Infection.
AB  - BACKGROUND: Data on associations between abdominal fat depot mass and subclinical
      atherosclerosis are limited, especially in women with HIV. METHODS: We assessed
      cross-sectional associations of dual X-ray absorptiometry scan-derived estimates
      of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT)
      with 3 measures of subclinical carotid artery atherosclerosis-carotid artery
      stiffness (Young's modulus of elasticity), presence of carotid artery lesions,
      and carotid artery intima-media thickness-in a subsample of participants in the
      Women's Interagency HIV Study. Statistical models adjusted for demographic
      variables, HIV serostatus, behavioral variables, and cardiovascular risk factors.
      RESULTS: There were 244 women with and 99 without HIV infection (median age 42,
      62% black). VAT mass (but not SAT) was associated with greater carotid artery
      stiffness in a fully adjusted linear regression model, including adjustment for
      SAT (beta = 11.3 log 10.N.m per kg VAT, 95% confidence interval: 1.0 to 21.7).
      Greater SAT mass was associated with lower odds of having a carotid artery lesion
      in a fully adjusted model, including adjustment for VAT [adjusted odds ratio,
      0.49 per kg of SAT (0.25 to 0.94)]. Neither VAT nor SAT was associated with
      carotid artery intima-media thickness. The VAT/SAT ratio was not statistically
      associated with any of the outcomes after covariate adjustment. CONCLUSIONS: In
      our cross-sectional study of women, the majority of whom had HIV, greater VAT
      mass was associated with increased carotid artery stiffness, whereas greater SAT
      mass was associated with a reduced odds of prevalent carotid artery lesions.

PMID- 29210841
TI  - Comparison of Heart Rate Variability Parameters to the Autonomic Reflex Screen in
      Postural Orthostatic Tachycardia Syndrome and Neurogenic Orthostatic Hypotension.
AB  - PURPOSE: The clinical significance of heart rate variability (HRV) in the context
      of autonomic dysfunction continues to be a matter of debate. Therefore, the
      purpose of the current study was to investigate the clinical relevance of HRV in
      the context of autonomic dysfunction. METHODS: Heart rate variability data from
      225 volunteers consisting of controls (n = 166) and patients with mild (n = 25)
      and severe (n = 34) autonomic dysfunction were retrospectively analyzed. Time and
      frequency parameters were correlated against baseline and standardized tests of
      autonomic function. RESULTS: During baseline, resting HR was negatively
      correlated with time (SD of all normal RR interval, r = -0.511; RMSSD, r = 
      0.585; pNN50, r = -0.545) and frequency (low-frequency, r = -0.362; high
      frequency, r = -0.421) parameters (P < 0.01). Resting systolic blood pressure
      demonstrated similar significant correlations (P < 0.01). During head-up tilt, SD
      of all normal RR intervals was positively correlated with [INCREMENT]HR and
      change in systolic blood pressure (r = 0.340; r = 0.538, respectively; P < 0.01).
      Similarly, low-frequency, high-frequency, and low-frequency/high-frequency ratios
      were correlated with [INCREMENT]HR (r = 0.422, r = 0.176, r = 0.470) and change
      in systolic blood pressure (r = 0.451, r = 0.407, and r = 0.185) (P < 0.01). Time
      parameters (SD of all normal RR intervals, RMSSD, and pNN50) were all
      significantly correlated with deep breathing (r = 0.600; r = 0.556; r = 0.516; P
      < 0.01, respectively). Low-frequency and high-frequency power were also
      correlated (r = 0.596; r = 0.580, respectively) (P < 0.01). CONCLUSIONS: Time and
      frequency parameters showed significant negative correlations with baseline
      hemodynamics. During a test of sympathetic activation and parasympathetic
      withdrawal, this relationship shifted to reveal significant positive correlations
      between HRV parameters and hemodynamics. Last, during a test of parasympathetic
      activation, there were significant positive correlations with cardiovagally
      mediated HRV parameters. Overall, these results suggest broader clinical
      relevance for HRV parameters within the spectrum of autonomic functioning.

PMID- 29210842
TI  - Electrodiagnostic Evidence of Berrettini Anastomosis.
AB  - PURPOSE: Cadaveric palmar dissections reveal an ulnar sensory crossover
      (Berrettini anastomosis) to the third common palmar nerve so frequently that this
      crossover is considered a normal part of the anatomy. No literature has
      documented electrophysiologic evidence of the Berrettini anastomosis (BA).
      Presentation of third digit ulnar sensory crossover waveforms. METHODS:
      Retrospective chart review case series. Clinical office. Nerve conduction
      waveforms and data. RESULTS: Ulnar stimulation sensory crossover waveforms to
      digit three consistent with BA are presented. CONCLUSIONS: Third digit BA is
      measurable in routine electrodiagnostic nerve conduction study in some patients.
      The observed BA latency is the same and the amplitude is smaller (25% to 33%)
      than the ulnar sensory response. The clinical significance of the BA sensory
      response is unclear. The presence of a BA in severe carpal tunnel syndrome may
      give a small amplitude normal latency sensory response that could be
      misinterpreted and lead to a false negative result.

PMID- 29210843
TI  - Intraoperative hypotension is associated with acute kidney injury in noncardiac
      surgery: An observational study.
AB  - BACKGROUND: Perioperative acute kidney injury (AKI) is common and increases the
      risk of morbidity and mortality. OBJECTIVES: To determine the association between
      intraoperative hypotension, defined as an individual decrease from baseline and
      the risk of perioperative AKI. DESIGN: Observational cohort study. SETTING:
      Karolinska University Hospital, Stockholm, Sweden, from October 2012 to May 2013
      and October 2015 and April 2016. PATIENTS: All adult patients undergoing major
      elective noncardiac surgery who were scheduled for an overnight admission in the
      postoperative unit were included. Patients undergoing phaeochromocytoma surgery
      were excluded. DATA COLLECTION: Preoperative risk factors (comorbidities),
      intraoperative events (hypotension defined as a more than 40 or 50% decrease in
      SBP relative to each patient's baseline and lasting more than 5 min) and
      postoperative data were collected from medical records. MAIN OUTCOME MEASURES:
      AKI within the first two postoperative days. RESULTS: Of the final cohort of 470
      patients, 127 (27%) developed AKI in the perioperative period. AKI was associated
      with male sex [(66 vs. 48%) P < 0.001], a higher preoperative creatinine (81 vs.
      73 MUmol l, P = 0.003), American Society of Anaesthesiologists class more than
      two (54 vs. 42%, P = 0.014) and preoperative hypertension (54 vs. 40%, P =
      0.005). During surgery, the AKI subgroup had more hypotensive events (>40%, 70
      vs. 57%, P = 0.013; >50%, 20 vs. 12%, P = 0.024) and greater blood loss (800 vs.
      400 ml, P < 0.001). Postoperatively, in AKI patients a positive fluid balance was
      more common (3123 vs. 2700 ml, P < 0.001), as was 30-day mortality (4 vs. 1%, P <
      0.005). Multivariate analyses demonstrated that an intraoperative reduction of
      SBP more than 50% was associated with a more than doubled risk of AKI, adjusted
      odds ratio 2.27; 95% CI, 1.20 to 4.30, P = 0.013. CONCLUSION: In patients
      undergoing noncardiac surgery, there was a high incidence of perioperative AKI.
      Intraoperative avoidance of hypotension may decrease the risk of AKI.

PMID- 29210844
TI  - Ultrasound examination of the antrum to predict gastric content volume in the
      third trimester of pregnancy as assessed by MRI: A prospective cohort study.
AB  - BACKGROUND: Ultrasound examination of the gastric antrum allows reliable pre
      operative assessment of gastric contents and volume in adult patients. However,
      during pregnancy, the change in the anatomical position of the stomach due to the
      gravid uterus leads to a change in the measured value of the antral area.
      Therefore, current mathematical models predicting gastric content volume (GCV) in
      the adult may not apply in term pregnant women. OBJECTIVE: To propose a
      mathematical model which is predictive of GCV in pregnant women and to assess the
      performance of an ultrasound qualitative grading scale (0 to 2) for the diagnosis
      of clear fluid volumes more than 0.8 and 1.5 ml kg. DESIGN: Prospective cohort
      study. SETTING: Hospices Civils de Lyon, Hopital Femme Mere Enfant, Lyon and
      Assistance Publique - Hopitaux de Marseille, Hopital Nord, Marseille, France.
      PATIENTS: Pregnant women in the third trimester of pregnancy. MAIN OUTCOME
      MEASURES: Comparison of the GCV as measured by MRI and the ultrasound measured
      antral cross-sectional area, and an assessment of gastric contents according to a
      0 to 2 qualitative grading scale. RESULTS: Data from 34 women were analysed. A
      linear model predictive of GCV was constructed with a 95% agreement band of +/-95
      ml, with a mean polar angle of -8.7 degrees . Performance of the qualitative
      grading scale to detect fluid volumes >0.8 and >1.5 ml kg was improved when used
      in a composite scale including a 505 mm antral area cut-off value in the
      semirecumbent supine position. CONCLUSION: We report a new mathematical model
      predictive of GCV in women in the third trimester of pregnancy. Furthermore, the
      combination of the qualitative and the quantitative ultrasound examination of the
      gastric antrum might be useful to assess gastric fluid volume in pregnant women.
      TRIAL REGISTRATION: ANSM Register N degrees 2015-A00800-49.

PMID- 29210845
TI  - Does a hypnosis session reduce the required propofol dose during closed-loop
      anaesthesia induction?: A randomised controlled trial.
AB  - BACKGROUND: Hypnosis has a positive effect on peri-operative anxiety and pain.
      OBJECTIVE: The objective of this study was to assess the impact of a formal deep
      hypnosis session on the consumption of propofol for anaesthetic induction using
      automated administration of propofol guided by the bispectral index (BIS) in a
      closed loop. DESIGN: A 1 : 1 randomised, usual-care-controlled, single-centre
      trial. SETTING: Tertiary care centre in France from April 2014 to December 2015.
      PATIENTS: Female adult patients scheduled for outpatient gynaecological surgery
      under general anaesthesia. INTERVENTION: Before surgery, patients were randomised
      to receive either a deep hypnosis session or routine care. Anaesthetic induction
      was performed automatically by propofol without opioids and was assisted by the
      BIS in a closed loop. MAIN OUTCOME MEASURES: The primary endpoint was the
      propofol dose required for anaesthesia induction, defined as a BIS less than 60
      for at least 30 s. RESULTS: Data for 31 patients in the hypnosis group and 35 in
      the control group were analysed. There was no evidence of a difference in the
      mean required propofol dose for anaesthetic induction between the hypnosis and
      the control groups (2.06 mg kg (95% confidence interval [1.68 to 2.43]) versus
      1.79 mg kg (95% CI [1.54 to 2.03]), P = 0.25, respectively). CONCLUSION: The
      current study, which was designed to determine the effect of a deep hypnosis
      session on anaesthesia induction using an automated tool for propofol
      administration, failed to detect a difference in the required dose of propofol.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT02249364.

PMID- 29210847
TI  - Navigating the patient-generated health data deluge.

PMID- 29210848
TI  - Stethoscopes: Friend or fomite?

PMID- 29210849
TI  - Inspiring followership.

PMID- 29210850
TI  - Graduate education options for your baccalaureate-prepared nurses.

PMID- 29210851
TI  - Cultivating a high-performing team.
AB  - Discover how one group successfully sustained HCAHPS scores in the 99th
      percentile over 18 quarters.

PMID- 29210852
TI  - Workplace culture and patient outcomes: What's the connection?

PMID- 29210853
TI  - Double vision: When a dying patient's family member is also a nurse.

PMID- 29210854
TI  - Nurse executive professional development.

PMID- 29210855
TI  - The motivation to stay motivated.

PMID- 29210856
TI  - Outcome standardization to blood pressure reduction in meta-analyses: sailing in
      uncharted waters.

PMID- 29210857
TI  - The perils of determining cardiovascular risk in relation to home blood pressure.

PMID- 29210858
TI  - What is the most appropriate target SBP in persons with hypertension and diabetes
      mellitus?

PMID- 29210859
TI  - Catheter-based renal denervation in hypertension: heading for new shores.

PMID- 29210860
TI  - Aortic dilatation in Marfan syndrome: role of arterial stiffness and fibrillin-1
      variants.
AB  - OBJECTIVE: Marfan syndrome (MFS) is an autosomal dominant genetic disorder
      characterized by aortic root dilation and dissection and an abnormal fibrillin-1
      synthesis. In this observational study, we evaluated aortic stiffness in MFS and
      its association with ascending aorta diameters and fibrillin-1 genotype. METHODS:
      A total of 116 Marfan adult patients without history of cardiovascular surgery,
      and 144 age, sex, blood pressure and heart rate matched controls were enrolled.
      All patients underwent arterial stiffness evaluation through carotid-femoral
      pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen
      tonometer). Fibrillin-1 mutations were classified based on the effect on the
      protein, into 'dominant negative' and 'haploinsufficient' mutations. RESULTS: PWV
      and central pulse pressure were significantly higher in MFS patients than in
      controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008;
      41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P < 0.0001], with a higher age
      related increase of PWV in MFS (beta 0.062 vs. 0.036). Pressure amplification was
      significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P <
      0.0001]. Central pressure profile was altered even in MFS patients without aortic
      dilatation. Multiple linear regression models showed that PWV independently
      predicted aortic diameters at the sinuses of Valsalva (beta = 0.243, P = 0.002)
      and at the sinotubular junction (beta = 0.186, P = 0.048). PWV was higher in
      'dominant negative' than 'haploinsufficient' fibrillin-1 mutations [7.37 (7.04
      7.70) vs. 6.60 (5.97-7.23) m/s, P = 0.035], although this difference was not
      significant after adjustment. CONCLUSION: Aortic stiffness is increased in MFS,
      independently from fibrillin-1 genotype and is associated with diameters of
      ascending aorta. Alterations in central hemodynamics are present even when aortic
      diameter is within normal limits. Our findings suggest an accelerated arterial
      aging in MFS.

PMID- 29210861
TI  - Risk of stroke and coronary heart disease among various levels of blood pressure
      in diabetic and nondiabetic Chinese patients.
AB  - OBJECTIVE: To compare the risk of stroke and coronary heart disease (CHD) among
      various blood pressure (BP) levels in diabetic and people without diabetes
      Chinese patients. METHODS: This cross-sectional study was part of Prospective
      Urban Rural Epidemiology China study. Patients aged 35 to70 years were recruited
      from 12 provinces of China between 2005 and 2009. The participants were
      classified into three groups: hypertension (HTN), high normal BP, and normal BP,
      and also into SBP and DBP quintiles. RESULTS: A total of 42 959 patients were
      analyzed with 38 975 (90.7% of total population) people without diabetes and 3984
      (9.3% of total population) diabetic patients. Among diabetic patients, the HTN
      group was associated with an increased risk of stroke (odds ratio, 3.03; 95%
      confidence interval, 1.47-6.25) and CHD (odds ratio, 2.21; 95% confidence
      interval, 1.45-3.38), when compared with normal BP group. Similar results were
      drawn in nondiabetic patients. However, no significant difference in risk of
      stroke or CHD was found between high normal BP and normal BP groups in either
      diabetic or nondiabetic patients. Risk of CHD and stroke increased significantly
      when SBP was above 125 mmHg or DBP above 72 mmHg in people without diabetes,
      whereas this trend was attenuated in diabetic patients. CONCLUSION: HTN was
      associated with a two-fold increased risk of CHD and a three-fold increased risk
      of stroke compared with normotension irrespective of diabetes status. For
      diabetic patients with HTN, a more comprehensive method is essential for
      assessing cardiovascular risk.

PMID- 29210862
TI  - Renal sympathetic denervation in Sweden: a report from the Swedish registry for
      renal denervation.
AB  - BACKGROUND: Renal denervation (RDN) is a catheter-based intervention to treat
      patients with resistant hypertension. The biological effects of RDN are not fully
      understood, and randomized controlled trials have generated conflicting evidence.
      This report presents data from the Swedish Registry for Renal Denervation, an
      investigator-driven nationwide registry. PURPOSE: To assess the safety and
      efficacy of RDN on patients with resistant hypertension in a real-world clinical
      setting. METHODS: This nationwide database contains patient characteristics,
      procedural details, and follow-up data on all RDN procedures performed in Sweden.
      Consecutive procedures between 2011 and 2015 were included. RESULTS: The data
      analysis consists of 252 patients (mean age 61 +/- 10 years, 38% women; mean 4.5
      +/- 1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood
      pressure (BP) decreased 6 months after RDN (176 +/- 23/97 +/- 17 to 161 +/- 26/91
      +/- 16 mmHg, both P < 0.001; and 155 +/- 17/89 +/- 14 to 147 +/- 18/82 +/- 12
      mmHg, both P < 0.001). Significant office and ambulatory BP reductions persisted
      throughout the observation period of 36 months. Major procedure-related vascular
      complications occurred in four patients. Renal function and number of
      antihypertensive drugs were unchanged during follow-up. CONCLUSION: In this
      complete national cohort, RDN was associated with a sustained reduction in office
      and ambulatory BP in patients with resistant hypertension. The procedure proved
      to be feasible and associated with a low-complication rate, including long-term
      adverse events.

PMID- 29210863
TI  - Prevalence, awareness, treatment, and control of hypertension among rural and
      urban dwellers of the Far North Region of Cameroon.
AB  - OBJECTIVE: To assess the prevalence and determinants of high blood pressure (BP)
      and awareness, treatment, and control rates in the Far North Region of Cameroon,
      where these variables have not been explored so far. METHODS: In total, 889
      individuals (41.5% women) aged at least 18 years participated in a cross
      sectional survey conducted in Maroua (urban area) and Tokombere (rural area) from
      November 2014 to May 2015, using a multistage cluster sampling frame.
      Anthropometric variables, BP, and fasting capillary glucose were assessed in all
      participants. Hypertension was defined as BP at least 140/90 mmHg or
      antihypertensive therapy and BP control as BP less than 140/90 mmHg. Prevalence
      estimates were age standardized to the Cameroon population. RESULTS: The
      prevalence of hypertension was 37.8% (rural: 34%; urban: 41.2%; men: 38.8%;
      women: 37.9%). Hypertension was associated with urban environment (odds ratio:
      1.42; 95%; confidence interval 1.06-1.89), age at least 70 years (4.06; 2.02
      6.14), male sex (4.06; 2.02-6.14), abdominal obesity (2.36; 1.54-3.61), and high
      blood sugar (2.01; 1.31-3.08). Among individuals with hypertension, 18.6% (rural:
      17.9%; urban: 19.5%) were aware of having high BP. Among those aware, 29.3%
      (rural: 17.3%; urban: 36.3%) reported receiving treatment, of whom 16.3% (rural:
      22.6%; urban: 4.2%) had BP controlled. Awareness, treatment, and BP control
      levels were higher in women than men. CONCLUSION: Hypertension is highly
      prevalent in Far North Cameroon and awareness, treatment, and control rates are
      low. Efforts to improve detection, treatment, and control of hypertension in
      Cameroon are needed.

PMID- 29210864
TI  - Geographical variations in hypertension prevalence, awareness, treatment and
      control in China: findings from a nationwide and provincially representative
      survey.
AB  - OBJECTIVES: Hypertension has been the most important risk factor for disease
      burden in China. We aimed to conduct the first national spatial analysis of
      hypertension status, awareness, treatment and control in China. METHODS:
      Choropleth maps were used to examine the spatial patterning of hypertension,
      awareness, treatment and control in a nationally and provincially representative
      sample of 174 389 adults from the 2013 to 2014 China Chronic Disease and Risk
      Factors Surveillance. Multilevel regressions were used to analyze each outcome
      across provinces, counties, towns and villages/residential committees and to test
      the proportion of area-level variances explained by known risk factors. RESULTS:
      Hypertension prevalence was highest in the north (e.g. Liaoning = 37.7%) and
      lowest in the south (e.g. Hainan = 17.9%). Among participants found to have
      hypertension, awareness was generally low, especially in the south (e.g. Guizhou
      = 18.0%). Receipt of treatment among those who were aware of their hypertension
      status was above 70% in all provinces except for Tibet (37.7%) and Guizhou
      (54.5%). Control of hypertension among those receiving treatment (SBP < 140 and
      DBP < 90 mmHg) was generally low, especially in northeastern and southwestern
      provinces. Adjustment for demographic, socioeconomic and behavioral factors,
      weight status, healthcare use and urbanization of residence accounted for 57.7%
      of variation between provinces in hypertension status, 48.5% in awareness, 47.6%
      in treatment and 18.0% in control. CONCLUSION: Hypertension is spatially
      patterned in China and there is an unmet need at each step from diagnosis to
      receiving treatment and achieving controlled hypertension. Geographically
      targeted strategies are required to enhance hypertension prevention and
      management in China.

PMID- 29210865
TI  - Severe Serotonin Syndrome in an Autistic New Psychoactive Substance User After
      Consumption of Pills Containing Methoxphenidine and alpha-Methyltryptamine.

PMID- 29210866
TI  - Abrupt Improvement in Obsessive-Compulsive Symptoms Upon Discontinuation of
      Clozapine.

PMID- 29210867
TI  - Antipsychotic Polypharmacy and Its Relation to Metabolic Syndrome in Patients
      With Schizophrenia: An Egyptian Study.
AB  - PURPOSE/BACKGROUND: Few studies have examined the relationship between
      antipsychotic polypharmacy and metabolic syndrome in schizophrenia. Some studies
      suggest that antipsychotic polypharmacy may be associated with greater metabolic
      risk, whereas other studies suggest that this is uncertain. To date, there have
      been no studies in Egypt or the Arab world that have investigated this
      relationship. We sought to compare subjects with schizophrenia receiving
      antipsychotic polypharmacy and monotherapy as regards metabolic outcomes and to
      investigate medication-related factors associated with metabolic syndrome.
      METHODS/PROCEDURES: We recruited 118 subjects with schizophrenia and compared
      between those receiving antipsychotic polypharmacy (86 subjects) and monotherapy
      (32 subjects) as regards demographic, clinical, metabolic, and antipsychotic
      medication characteristics. We examined the effect of antipsychotic-related
      factors an outcome of metabolic syndrome. FINDINGS/RESULTS: The prevalence of
      metabolic syndrome in our sample was 38.1%. Except for gender, there was no
      statistically significant difference as regards demographic and clinical
      characteristics, rates of metabolic syndrome, or for individual metabolic
      parameters. We found a statistically significant difference (P < 0.05) between
      the 2 groups as regards the number, dose, and duration of intake and for the
      number of subjects receiving typical antipsychotics (oral and depot) and a number
      of individual antipsychotic medications. Using logistic regression, receiving
      haloperidol depot was the only antipsychotic-related factor predictive for
      metabolic syndrome. IMPLICATIONS/CONCLUSIONS: The prevalence of metabolic
      syndrome does not differ in schizophrenia whether patients are receiving
      polypharmacy and monotherapy nor do they differ for individual metabolic
      parameters. Most antipsychotic-related characteristics did not predict for
      metabolic syndrome.

PMID- 29210868
TI  - Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of
      the European Medicines Agency/European Medicines Agency Adverse Drug Reactions'
      Database.
AB  - PURPOSE/BACKGROUND: A recent years' increase in both prescribing and availability
      of second-generation antipsychotics (SGAs) has been observed. According to the
      literature, typically made up by case studies/series, quetiapine seems to be the
      most commonly misused SGA, with both intranasal and intravenous intake modalities
      having been described. Another SGA that has been anecdotally reported to be
      misused is olanzapine. For these molecules, both a previous history of drug
      misuse and being an inmate have been described as factors associated with misuse.
      Hence, while providing here an updated literature review of the topic, we aimed
      at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as
      reported to the European Medicines Agency's EudraVigilance (EV) database; this
      was carried out in comparison with the reference drug olanzapine. METHODS: All
      spontaneous, European Medicines Agency database reports relating to both
      quetiapine (2005-2016) and olanzapine (2004-2016)
      misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive
      analysis was performed. RESULTS: From the EV database, 18,112 (8.64% of 209,571)
      and 4178 (7.58% of 55,100) adverse drug reaction reports of
      misuse/abuse/dependence/withdrawal were associated with quetiapine and
      olanzapine, respectively. The resulting proportional reporting ratio values
      suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse
      drug reactions were more frequently reported for quetiapine (1.07, 1.01, and
      5.25, respectively) in comparison with olanzapine. CONCLUSIONS: Despite data
      collection limitations, present EV data may suggest that, at least in comparison
      with olanzapine, quetiapine misuse may be a cause for concern.

PMID- 29210869
TI  - Treatment of Behavioral Disinhibition in Huntington's Disease With Valproic Acid.

PMID- 29210870
TI  - Learning Needs of Hospitalized Patients With Heart Failure in Singapore: A
      Descriptive Correlational Study.
AB  - BACKGROUND: Understanding the learning needs of patients with heart failure (HF)
      is important in reducing the incidence of HF-related hospital readmissions.
      Sociocultural differences are known to influence patient learning needs. However,
      most HF learning needs studies have been conducted on Western populations.
      PURPOSE: The aim of this study was to investigate the learning needs of
      hospitalized patients with HF in Singapore. METHODS: A cross-sectional,
      descriptive correlational design was adopted using a questionnaire survey that
      included the Heart Failure Learning Needs Inventory and sociodemographic and
      clinical datasheets. A convenience sample of 97 patients with HF was recruited
      from an acute hospital in Singapore. RESULTS: Findings revealed that education
      topics relating to signs and symptoms, risk factors, general HF information, and
      medications were perceived by participants as the most important. Contrastingly,
      education topics relating to diet, activity, and psychological factors were
      poorly valued. The only significant demographic factor that was correlated to the
      patients' learning needs was monthly household income, which correlated to
      education on HF risk factors and general HF information. CONCLUSIONS: This study
      supports the necessity of carefully prioritizing patient education topics in line
      with patient learning needs. Furthermore, education should be culturally
      sensitive and take into account the unique values, needs, and situations of
      patients.

PMID- 29210871
TI  - Self-limiting Conditions: A Holistic Approach.

PMID- 29210872
TI  - New Nursing Faculty and Incivility: Applying Mindfulness-Based Strategies.
AB  - Workplace incivility remains a problem within the nursing profession. As nurse
      leaders, we must recognize and not ignore the complexity of cultures that have
      adapted incivility into the work environment. Nursing education is a discipline
      that requires collaborative team work, independent drive, and commitment. New
      nursing faculty experiencing incivility can use mindfulness-based meditation
      approaches to cope with uncivil behaviors experienced within the workplace. Nurse
      educators applying the concepts of mindfulness can learn how to provide
      themselves self-care by reducing stress, as enhanced daily awareness of peace and
      calm are incorporated into their lifestyle. Mindfulness provides a realization
      that control can only be given to other persons when an individual allows or
      accepts another's negative behaviors. Awareness of the value and importance of
      oneself can assist the nurse educator experiencing incivility to maintain his or
      her emotional, physical, and spiritual health despite the volatility of the work
      environment.

PMID- 29210873
TI  - The Effect of Aromatherapy on Sleep Quality of Elderly People Residing in a
      Nursing Home.
AB  - BACKGROUND: Sleep is important for health and quality of life in the elderly, and
      sleep disturbances are reported to be associated with many of the adverse medical
      conditions. PURPOSE: This research was carried out to evaluate the effect of
      inhalation of lavender oil on sleep quality of nursing home residents. METHODS: A
      questionnaire was used to evaluate sociodemographic characteristics and sleeping
      properties of the 30 volunteers, enrolled. Pittsburgh Sleep Quality Index was
      applied as a pre- and posttest to measure sleep quality of individuals who
      inhaled lavender oil drops on the pillows every evening for a week before
      sleeping. RESULTS: Before and after aromatherapy, the mean Pittsburgh Sleep
      Quality Index score of the nursing home residents was (Equation is included in
      full-text article.)= 6.0 +/- 5.1 and (Equation is included in full-text
      article.)= 2.6 +/- 3.4, respectively, whereas statistically significant
      difference was not observed for independent variables. Cronbach alpha reliability
      coefficient of the Pittsburgh Sleep Quality Index scale was found to be 0.816.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicated an improvement of
      sleep quality of nursing home residents after the application of aromatherapy
      with lavender oil.

PMID- 29210874
TI  - Ischemic Stroke Patients' Decision-Making Process in Their Use of Western
      Medicine and Alternative and Complementary Medicine.
AB  - Stroke is ranked third among the top 10 causes of death in Taiwan. Besides a high
      mortality rate, stroke survivors are often left with physical or functional
      sequela. This study aimed to explore ischemic stroke patients' decision-making
      process using Western medicine (WM) and complementary and alternative medicine
      (CAM). This study is a qualitative study based on grounded theory. A total of 12
      participants were recruited. Findings revealed that the participants accepted WM
      and CAM treatments following the onset of ischemic stroke. Three categories and
      several subcategories emerged from stroke patients' decision-making process.
      These are "uncertainty of stroke," "delicate balance between WM and CAM," and
      "reestablishing confidence and faith." Eventually, they exhibited the core
      category of "breakthrough and the pursuit of a sense of rebirth." This study also
      found that the participants were unwilling to inform their health care
      professionals on their use of CAM. Therefore, health care professionals should
      empathize with the views and needs of their patients and respect their decision
      to combine WM with CAM. The views of other medical teams concerning CAM into
      their analysis of patients' decision-making process are recommended. Therefore,
      comprehensive insight into ischemic stroke patients' decision-making process for
      using CAM can be further explored.

PMID- 29210875
TI  - Comparison of the Effects of Benson Muscle Relaxation and Nature Sounds on the
      Fatigue in Patients With Heart Failure: A Randomized Controlled Clinical Trial.
AB  - This study was conducted with the aim of comparing the effects of Benson muscle
      relaxation and nature sounds on fatigue in patients with heart failure. Fatigue
      and exercise intolerance as prevalent symptoms experienced by patients with heart
      failure can cause the loss of independence in the activities of daily living. It
      can also damage self-care and increase dependence to others, which subsequently
      can reduce the quality of life. This randomized controlled clinical trial was
      conducted in an urban area of Iran in 2016. Samples were consisted of 105
      hospitalized patients with heart failure chosen using a convenience sampling
      method. They were assigned to relaxation, nature sounds, and control groups using
      a randomized block design. In addition to routine care, the Benson muscle
      relaxation and nature sounds groups received interventions in mornings and
      evenings twice a day for 20 minutes within 3 consecutive days. A 9-item
      questionnaire was used to collect data regarding fatigue before and after the
      interventions. Relaxation and nature sounds reduced fatigue in patients with
      heart failure in comparison to the control group. However, no statistically
      significant difference was observed between the interventions. Benson muscle
      relaxation and nature sounds are alternative methods for the reduction of fatigue
      in patients with heart failure. They are inexpensive and easy to be administered
      and upon patients' preferences can be used by nurses along with routine nursing
      interventions.

PMID- 29210876
TI  - Identifying the Factors Affecting Comfort and the Comfort Levels of Patients
      Hospitalized in the Coronary Care Unit.
AB  - Comfort, a concept associated with the art of nursing, is important for reducing
      the negative impact of hospitalization in a coronary care unit (CCU). Providing
      nursing interventions that ensure patient comfort is important for patients to
      respond positively to treatment. To determine the factors affecting comfort and
      the comfort levels of patients hospitalized in the CCU. A descriptive study. The
      study was conducted between December 2015 and February 2016 in the CCU of a state
      hospital located in Trabzon, Turkey. The sample consisted of 119 patients who
      complied with the criteria of inclusion for the study. Data were collected using
      the "Patient Information Form" and a "General Comfort Questionnaire." The mean
      patient comfort score was 3.22 +/- 0.33, and we found significant relationships
      between comfort scores and age (r = -0.19; P = .03) and communication by nurses
      and physicians (P < .05). Regression analysis revealed that sufficient
      communication by physicians, education level, age, and having a companion were
      related to the comfort level (P < .05). Communication by nurses and physicians
      and having a companion could change the comfort levels of patients hospitalized
      in the CCU.

PMID- 29210877
TI  - Music Intervention With Reminiscence Therapy and Reality Orientation for Elderly
      People With Alzheimer Disease Living in a Nursing Home: A Pilot Study.
AB  - The purpose of this study was to investigate the effect of an 8-week nursing
      intervention consisting of 2 weekly sessions of music and reminiscence therapy
      together with the application of reality orientation techniques. Our expectation
      at the onset of the study was that listening to music that was familiar and
      connected with the memory of past events would, due to the music's emotional
      impact, stimulate memory associations, leading, in turn, to a positive effect on
      depression and anxiety in people living with dementia. We carried out a pre
      /posttest intervention design with a sample of 19 patients divided into 2 groups
      a 10-patient control group and a 9-patient intervention group-in a nursing home
      in Spain. Goldberg tests for depression and anxiety have been assessed at
      baseline and postintervention in both groups. Our results confirm the valuable
      effect of music therapy and reminiscence therapy together with reality
      orientation techniques on depression in patients with mild Alzheimer disease. Our
      study may constitute an important starting point for further research on nursing
      interventions based on the provision of music and/or reminiscence therapy
      together with reality orientation techniques that is implemented on a daily basis
      in nursing homes.

PMID- 29210878
TI  - Integrative Neuronutritional Therapy Metabolic Brain Parameters in Mental Health.

PMID- 29210880
TI  - In Reply.

PMID- 29210879
TI  - The Interconnectedness of Climate, Weather, and Living Organisms' Health.

PMID- 29210881
TI  - Do social determinants of health make a difference in the age at natural
      menopause in Canada?

PMID- 29210882
TI  - Fluency in Nursing Education and Simulation: A Concept Analysis.
AB  - AIM: The aim of the study was to realign how nurses view simulation in nursing
      education as a means of facilitating fluency in knowledge and action to promote
      expertise in practice. BACKGROUND: Nursing expertise is attained by translating
      complex phenomena across multiple representations and by constructing meaning
      through experience. Simulation provides learners the experiences necessary to
      develop fluency in thought and action. METHOD: Procedures outlined by Hupcey and
      Penrod (2005) and Walker and Avant (2011) were used to identify uses, defining
      attributes, philosophical assumptions, contextual factors, and values of the
      concept. RESULTS: Use of simulation to promote representational fluency in other
      disciplines fosters deep conceptual understanding and skillfulness, which
      prepares learners to perform with fluidity and expertise. CONCLUSION: The
      association between representational fluency and simulation introduces nurse
      educators to a way of thinking about how novices learn to think and act like
      experts. Further research is recommended.

PMID- 29210883
TI  - Association between pain and sexual health in older people: results from the
      English Longitudinal Study of Ageing.
AB  - There is little information on the impact of pain on sexual health in later life.
      The aim of this analysis was to determine the association between self-reported
      pain and sexual health in older men and women. Data were collected for the
      nationally representative English Longitudinal Study of Ageing. Community
      dwelling adults aged 50 years and older completed the Sexual Relationships and
      Activities Questionnaire in Wave 6 (2012/2013). Participants were asked (waves 1
      6 [2002-2013]) whether they were "often troubled with pain" and, how severe was
      their pain; mild, moderate, or severe. The association between pain and sexual
      health was assessed using logistic regression. Analyses were stratified by sex,
      with adjustments made for age followed by adjustments for health and lifestyle
      factors, depressive symptoms, and socioeconomic status. Of the 3916 participants
      who reported having sexual activity in the past year, 28% of women and 23% of men
      reported experiencing moderate or severe pain often at Wave 6. After adjusting
      for age, compared with men experiencing no pain, men with moderate or severe pain
      reported less frequent intercourse and masturbation, more erectile difficulties,
      and more concerns about their sexual health. After age adjustment, there were no
      associations between pain severity and sexual health among women. Of the 1872
      participants with a cumulative pain score, there were significant associations
      between reporting pain and concerns about sexual health in both men and women.
      Pain was associated with impairment in sexual health in men and women; however,
      the effect was more marked in men.

PMID- 29210884
TI  - Discrepancy Between Cerebral Structure and Cognitive Functioning: A Review.
AB  - Neuroscientists typically assume that human mental functions are generated by the
      brain and that its structural elements, including the different cell layers and
      tissues that form the neocortex, play specific roles in this complex process.
      Different functional units are thought to complement one another to create an
      integrated self-awareness or episodic memory. Still, findings that pertain to
      brain dysplasia and brain lesions indicate that in some individuals there is a
      considerable discrepancy between the cerebral structures and cognitive
      functioning. This seems to question the seemingly well-defined role of these
      brain structures. This article provides a review of such remarkable cases. It
      contains overviews of noteworthy aspects of hydrocephalus, hemihydranencephaly,
      hemispherectomy, and certain abilities of "savants." We add considerations on
      memory processing, comment on the assumed role of neural plasticity in these
      contexts, and highlight the importance of taking such anomalies into account when
      formulating encompassing models of brain functioning.

PMID- 29210887
TI  - Composition and Associated Factors of Radiological Examination in Major Trauma
      Patients: A Prospective Observational Study.
AB  - The care of major trauma patients continues to be a challenge for emergency
      physicians and trauma surgeons. We found that the total number of radiological
      examinations for major trauma patients in this study was high and mainly
      comprised radiography and computed tomography (CT), with CT being more commonly
      adopted. The number of CT scans was positively correlated with severity of injury
      and intensive care unit length of stay. Further study is warranted to optimize
      radiological examinations involving major trauma patients.This is an open-access
      article distributed under the terms of the Creative Commons Attribution-Non
      Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
      download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.

PMID- 29210888
TI  - Pneumonia in a Teenager Hiding a Fire-Eating Stunt.
AB  - Pneumonia in children due to hydrocarbon aspiration is usually the result of an
      uncommon accidental event. However, an acute and severe type of pneumonia induced
      by hydrocarbon aspiration is occasionally experienced by entertainers known as
      fire-eaters. Different approaches to treat fire-eater's pneumonia appear in the
      literature. Although there is no consensus regarding the management of this
      condition, the use of antibiotic therapy is well recognized and recommended by
      some, whereas others recommend only supportive treatment. Steroids are indicated
      in severe cases.Here, we report the case of a boy who developed severe pneumonia
      after inhaling hydrocarbons during an attempt to mimic a fire-eater show. Slow
      resolution was achieved after broad-spectrum antibiotic therapy in addition to
      systemic and inhaled steroids and physiotherapy.

PMID- 29210889
TI  - Does Specialty Training and Practice Setting Affect Adherence to the Pediatric
      Emergency Care Applied Research Network Criteria for Pediatric Head Trauma?
AB  - OBJECTIVE: The goal was to determine the effects of specialty training and
      practice settings on the adherence to the Pediatric Emergency Care Applied
      Research Network (PECARN) criteria. METHODS: A retrospective study was conducted
      on a 2-campus hospital. Chart documentation was used to determine adherence to
      PECARN criteria. Inclusion criteria were any traumatic head injury within 24
      hours in patients younger than 18 years over a 1-year period. Specialty training
      was subdivided into 3 groups: pediatric emergency medicine, emergency medicine
      (EM), and general pediatrics. The 2 hospital campuses are distinctly different
      practice settings, one being an academic practice setting, which is also a trauma
      center that has a dedicated pediatric emergency department, staffed by pediatric
      emergency medicine, EM, and general pediatrics physicians, and the second campus
      is a community practice and is staffed solely by EM physicians. Statistical
      analysis was performed using chi and Cochran-Mantel-Haenszel tests. All analyses
      were 2-sided, and P < 0.05 was considered statistically significant. RESULTS: A
      total of 709 pediatric patients with traumatic head injuries were analyzed.
      Overall adherence to PECARN criteria was 93%. No statistical difference was found
      between different specialty training on the academic campus. In addition, the
      rate of adherence among EM physicians at the academic and community settings was
      94.8% versus 86.5%, respectively (P = 0.004). CONCLUSIONS: Practice setting had
      an effect on adherence to PECARN criteria in pediatric patients with acute
      traumatic head injury. The same determination on adherence was not demonstrated
      among physicians with different specialty trainings.

PMID- 29210890
TI  - Allergic Colitis With Pneumatosis Intestinalis in an Infant.
AB  - Inflammatory causes of bloody diarrhea during infancy include necrotizing
      enterocolitis and allergic colitis, often due to cow's milk protein. We report
      this case of cow's milk protein allergy, managed successfully with elimination of
      dietary antigen, to highlight the unusual finding of pneumatosis intestinalis on
      abdominal x-ray, a radiographic hallmark associated with necrotizing
      enterocolitis. Detailed patient's history, clinical presentation, and physical
      examinations are discussed for cow's milk protein allergy and necrotizing
      enterocolitis.

PMID- 29210891
TI  - Debriefing to Improve Student Ability to Assess and Plan for the Care of Persons
      With Disability.
AB  - INTRODUCTION: Although recent literature suggests that students should be trained
      in the care of persons with disability (PWDs) as a form of cultural sensitivity
      (CS), healthcare professionals may receive limited experience during their formal
      training. After pharmacy students in 2 previous years of testing failed to
      adequately assess and plan for the care of a standardized patient's chief
      complaint and disability in an Objective Structured Clinical Examination (OSCE),
      the investigators added debriefing to the OSCE to determine if it would improve
      student's ability to assess and plan for the care of PWD. METHODS: Two
      sequentially enrolled second-year pharmacy school student cohorts participated in
      this study (control n = 90; intervention n = 82). During the OSCE, students
      interviewed and examined a standardized patient with a simulated physical
      disability and other chronic disease states. Students were then instructed to
      develop a care plan considering the patient's disability and other disease
      states. The intervention cohort received debriefing; the control did not.
      Students documented the care plan in a subjective, objective, assessment, and
      plan (SOAP) note. Investigators assessed SOAP note score (general ability of
      students to write a SOAP note) and CS score (specific ability to care for PWD) to
      determine the effectiveness of the debriefing. RESULTS: The intervention group
      showed a significantly higher percent mean CS score than the control group (93.6%
      +/- 19% and 61.1% +/- 30.7%, respectively, P < 0.001), translating to a mean of
      56.2/60 points earned for the intervention group and 36.7/60 points earned for
      the control group. Scores ranged from 0 to 60 points for both intervention and
      control groups. Students in the intervention group had an absolute improvement in
      pass rates (those students scoring >=70% on the OSCE) of 59.4% with 92.7% of the
      students passing in the intervention group versus 33.3% of the students passing
      in the control group (P < 0.001). The overall SOAP note scores were no different
      between the 2 cohorts (P = 0.353). CONCLUSIONS: Debriefing added to an OSCE
      improved students' performance in developing care plans for disabled patients.
      Ideally, longitudinal studies should be completed to determine if these skills
      transfer from debriefings to clinical practice. Development of effective training
      and assessment methods is essential for students to obtain adequate skills and
      knowledge to care for persons with disabilities.

PMID- 29210892
TI  - Physiologically Triggered Digital Cognitive Aid Facilitates Crisis Management in
      a Simulated Operating Room: A Randomized Controlled Study.
AB  - INTRODUCTION: Although the benefits of using cognitive aids in anesthesia care
      have previously been demonstrated, several challenges remain. It must be
      presented in a timely manner, and providers must be amenable to using the tool
      once it is available. We hypothesized that anesthesia residents would perform
      superiorly when presented with a digital cognitive aid (DCogA) that is
      automatically triggered by a set vital sign aberration. METHODS: Thirty
      anesthesia residents were randomized to either control (with access to hard copy
      of the cognitive aid) or receive a DCogA projected on their anesthesia
      information management system with the onset of heart block and associated
      hypotension. The scenario ended upon commencement of pacing, and the times to
      interventions were recorded. RESULTS: Fourteen participants were randomized to
      the control group and 16 to the intervention group DCogA. In the control group, 6
      of 14 participants failed to pace, and in the DCogA group, all participants
      initiated pacing (P < 0.01). Those in the DCogA group were also faster to pace
      [260.1 (137.5) s vs. 405.1 (201.8) s, P = 0.03]. Both groups were similar with
      respect to their knowledge of advanced cardiovascular life support as measured by
      a pretest (P = 0.92). CONCLUSIONS: We found those participants who were presented
      with electronic, physiologically triggered cognitive aids were more likely to
      appropriately treat heart block by initiating transcutaneous pacing. We believe
      that adoption of a high-functioning anesthesia information management system
      designed to detect physiologic perturbations and present appropriate decision
      support tools would lead to safer intraoperative care.

PMID- 29210893
TI  - Uterus Transplantation: A Rapidly Expanding Field.
AB  - Uterus transplantation (UTx) has been successfully introduced as a treatment
      option for women with absolute uterine factor infertility (AUFI). AUFI
      representing approximately 3% to 5% of the female general population is linked to
      either congenital uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome),
      major congenital uterine malformation (hypoplastic uterus, fraction of
      bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired
      condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that
      causes implantation failure or defect placentation. The world's first clinical
      uterus transplant was performed in 2000. However, a hysterectomy became necessary
      shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey
      reported on a surgically successful deceased donor transplant; however, this
      procedure has, to date, not resulted in a healthy live birth, the ultimate goal
      of UTx. Building on an extensive experimental background in various animal
      models, including primates, the Gothenburg group led by Brannstrom reported on
      the first delivery of a healthy baby in a recipient of a live donor UTx in 2014.
      This event did not only show the feasibility of UTx, it also helped defining
      relevant areas of clinical and basic research. Use of a gestational surrogate
      carrier, is, at least in theory, an alternative for a woman with AUFI seeking
      genetic motherhood. However, in the clear majority of countries worldwide,
      gestational surrogacy is not practiced based on legal, ethical, or religious
      concerns. Of note, the overwhelming majority of surveyed women in the United
      Kingdom, a country which permits surrogacy, preferred UTx over gestational
      surrogacy and adoption. Moreover, randomly selected women of fertile age in
      Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan
      with more than 3000 participants revealed that UTx had a twofold higher
      acceptance rate compared with gestational surrogacy. In a recent US survey
      exploring the potential of donating vascularized composite allografts, uterus
      donation achieved the highest priority. Thus, the acceptance of UTx as
      infertility treatment for women with AUFI is high, although the procedure remains
      in its infancy. Here, we provide an update of clinical activities, summarize
      achievements and challenges, and submit areas of research interests.

PMID- 29210894
TI  - Hypertension in Mozambique: trends between 2005 and 2015.
AB  - OBJECTIVE: To assess the current prevalence, awareness, treatment and control of
      arterial hypertension in Mozambican population, including adolescents and young
      adults, and to appraise their trends over the past decade, for the 25-64 years
      old population. METHODS: A cross-sectional study of a representative sample of
      the population aged 15-64 years (n = 2965) was conducted in 2014-2015, following
      the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Data from a
      survey conducted in 2005 using the same methodological approach was used to
      assess trends in the age group of 25-64 years. RESULTS: The prevalence of
      hypertension increased significantly, from 33.1 to 38.9% (P = 0.048), whereas
      awareness (2005 vs. 2014-2015: 14.8 vs. 14.5%, P = 0.914) and treatment among the
      aware (2005 vs. 2014-2015: 51.9 vs. 50.1%, P = 0.770) remained similar. Control
      among the treated increased (from 39.9 to 44.5%, P = 0.587), although not
      significantly. Mean blood pressure values increased (SBP: from 132.1 to 134.6
      mmHg, P = 0.089; DBP: from 78.2 to 82.5 mmHg, P < 0.001). Among participants aged
      15-24 years, in 2014-2015 the prevalence of hypertension was 13.1% (95%
      confidence interval: 9.8-16.4). CONCLUSION: Our findings show that the prevalence
      of hypertension in Mozambique is among the highest in developing countries, both
      in adults and adolescents, portraying an ample margin for reduction of the
      morbidity and mortality burden because of high blood pressure.

PMID- 29210895
TI  - Characteristics of upper-limb pull power and power endurance in Japanese female
      wrestlers.
AB  - This study aimed at elucidating the characteristics of upper-limb physical
      strength required by female wrestlers by comparing the pull power, power
      endurance, and number of repetitions between female wrestlers at world and
      national levels. The subjects were 20 female wrestlers (8 Olympic- and/or world
      class and 12 national-class top-ranking individuals). The subjects assumed a
      lying prone (face down) position on a bench and pulled a bar from arms length
      until contact with underside of bench. The weight load was increased in 10-kg
      steps and the upper-limb pull power was measured for each lift. To measure power
      endurance, the power to achieve the repetition maximum and the maximum number of
      repetitions were measured at the load at which they exerted their maximum power.
      All measurements were obtained using a GymAware power meter (Kinetic Performance
      Technology, Canberra, Australia). Pull power was greater at 20, 30, 40 and 50 kg
      in world-class wrestlers than in national-class wrestlers. No difference was
      observed in the time course of power endurance between the groups; however, the
      power in world-class wrestlers declined slower than in national-class wrestlers.
      Repetition maximum also tended to be higher in world-class wrestlers than in
      national-class wrestlers. Female wrestlers were observed to have greater upper
      limb pull power in a range from low to high loads and were able to preserve
      repetition ability while maintaining high power. Their competitive performance
      appears to be related to these abilities.

PMID- 29210896
TI  - Peer Training Using Cognitive Rehearsal to Promote a Culture of Safety in Health
      Care.
AB  - Nursing students need opportunities to prepare for real-world problems that they
      may encounter as they enter the profession. Incivility and bullying behaviors
      persist in health care. The purpose of this project was to increase students'
      awareness of incivility and prepare them to respond to it. Two teaching methods
      were compared. Results supported that interactive civility training using
      cognitive rehearsal provided by nursing student peers was as effective as
      instruction from an expert.

PMID- 29210897
TI  - Evaluation of Newly Licensed RNs to Determine Success of Nursing Program: A
      Partnership Between Practice and Education.

PMID- 29210898
TI  - Medication Errors Involving Nursing Students: A Systematic Review.
AB  - The purpose of this study was to synthesize the available empirical evidence on
      prelicensure nursing students' medication errors. A systematic literature review
      of original research publications was carried out. After the selection process,
      only 19 articles complied with all the requirements for inclusion in this review.
      The findings showed that few studies to date have analyzed errors and near misses
      involving nursing students, and the current evidence suggests that the incidence
      of them is high.

PMID- 29210899
TI  - Distinct Microbial Populations Exist in the Mucosa-associated Microbiota of
      Diarrhea Predominant Irritable Bowel Syndrome and Ulcerative Colitis.
AB  - GOALS: The goal of this study was to observe the bacterial colonization in the
      intestinal mucosa in the patients with diarrhea predominant irritable bowel
      syndrome (IBS-D) and ulcerative colitis (UC), and compare the mucosa-associated
      microbiota among the IBS-D patients, UC patients and the healthy control, and
      explore the correlation of the mucosa-associated microbiota with clinical
      manifestations. STUDY: A total of 20 IBS-D patients, 28 patients with UC (16
      active, 12 inactive) and 16 healthy subjects were enrolled in the study. They all
      underwent colonoscopies in the Gastrointestinal Endoscopy Center in the Second
      Affiliated Hospital of Xi'an Jiaotong University from June 2016 to October 2016.
      The mucosa specimens were taken at the junction of rectum and sigmoid colon for
      fluorescent in situ hybridization (FISH). Then the observed mucosa-associated
      microbiota was counted and compared. RESULTS: (1) In the IBS-D patients, the
      mucosa-associated bacteria were found to colonize in the surface of mucosa and
      the adjacent mucin layer. And in active UC, Escherichia coli, and Bacteroides
      were found in the lamina propria, in addition to bacterial colonization in the
      above-mentioned areas. (2) The total count of mucosa-associated bacteria and the
      individual counts of E. coli, Clostridium, and Bacteroides were significantly
      increased, and Bifidobacteria significantly decreased (P<0.05) in the IBS-D
      patients and UC patients. Counts of Lactobacillus were decreased only in UC
      patients compared with the healthy control. And a significantly larger variation
      of the above-mentioned bacterial counts was found in the patients with UC,
      particularly in those with active UC, compared with those with IBS-D (P<0.05);
      the counts in the UC group were 1.3 to 5.3 times more or less than those in the
      IBS-D group. (3) Compared with healthy controls and IBS-D, the total count of
      bacteria and the individual counts of E. coli and Bacteroides in the lamina
      propria in active UC were significantly increased (P<0.05). (4) A significant
      negative correlation of the counts of Lactobacillus and Bifidobacteria with the
      defecation frequency and fecal characteristics (P<0.05) was found in the IBS-D
      patients; in those with UC, both the total count of bacteria and the individual
      counts of E. coli, Clostridium, Bacteroides, Lactobacillus, and Bifidobacteria
      were significantly correlated, positively or negatively, with the related
      clinical manifestations and the activity of the disease (P<0.05). CONCLUSIONS:
      Compared with the healthy control, intestinal microecology was changed most
      obviously in UC with much smaller differences though in the same direction in IBS
      D. The translocation of some bacteria into the lamina propria was found in UC,
      particularly in active UC. The changes of mucosa-associated microbiota were
      related more or less to some clinical manifestations in IBS-D and UC.

PMID- 29210900
TI  - Development of Image-enhanced Endoscopy of the Gastrointestinal Tract: A Review
      of History and Current Evidences.
AB  - Endoscopy imaging of the gastrointestinal (GI) tract has evolved tremendously
      over the last few decades. Key milestones in the development of endoscopy imaging
      include the use of various dyes for chromoendoscopy, the application of optical
      magnification in endoscopy, the introduction of high-definition image capturing
      and display technology and the application of altered illuminating light to
      achieve vascular and surface enhancement. Aims of this review paper are to
      summarize the development and evolution of modern endoscopy imaging and in
      particular, imaged-enhanced endoscopy (IEE), to promote appropriate usage, and to
      guide future development of good endoscopy practice. A search of PubMed database
      was performed to identify articles related to IEE of the GI tract. Where
      appropriate, landmark trials and high-quality meta-analyses and systematic
      reviews were used in the discussion. In this review, the developments and
      evolutions in endoscopy imaging and in particular, IEE, were summarized into
      discernible eras and the literature evidence with regard to the strengths and
      weaknesses in term of their detection and characterization capability in each of
      these eras were discussed. It is in the authors' opinion that IEE is capable of
      fairly good detection and accurate characterization of various GI lesions but
      such benefits may not be readily reaped by those who are new in the field of
      luminal endoscopy. Exposure and training in making confident diagnoses using
      these endoscopy imaging technologies are required in tandem with these new
      developments in order to fully embrace and adopt the benefits.

PMID- 29210901
TI  - Smoking Habits are Strongly Associated With Colorectal Polyps in a Population
      based Case-control Study.
AB  - GOALS: The goal of this study is to test the association between lifetime smoking
      habits and colorectal polyps of different classifications. BACKGROUND: Smoking is
      an established risk factor for several cancers, including colorectal cancer.
      However, the association between lifetime smoking habits including intensity,
      duration, and cessation, and premalignant colorectal polyps is yet to be
      established. STUDY: A case-control study among 828 consecutive subjects aged 40
      to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria
      were: medically treated diabetes, colectomy, and belonging to colorectal cancer
      high risk group. Polyps were stratified according to histology (serrated or
      adenomatous polyp) and location. All participants underwent anthropometric
      measurements and a structured medical and lifestyle interview. RESULTS: Current
      smoking was more strongly associated with increased odds for distal rather than
      proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68
      and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than
      adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively).
      All levels of smoking intensity (daily cigarettes) were associated with
      colorectal polyps. A dose-response association was seen between smoking duration
      and colorectal polyps. Smoking duration of >=20 years was strongly associated
      with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential
      confounders, smoking intensity and years since smoking cessation. All
      associations were stronger for distal serrated polyps. CONCLUSIONS: Smoking
      duration is associated with colorectal plyps, independently of other potential
      confounders, smoking intensity, and cessation. The association is stronger with
      distal rather than proximal polyps, and with serrated polyps rather than
      adenomas.

PMID- 29210902
TI  - Insufflation With Carbon Dioxide During Pediatric Colonoscopy for Control of
      Postprocedure Pain.
AB  - GOALS: To determine if carbon dioxide (CO2) insufflation in children would
      improve postprocedure pain following colonoscopy in children. BACKGROUND: CO2
      insufflation during colonoscopy has been found to reduce postcolonoscopy pain in
      the adult population, but limited data exist in pediatrics. MATERIALS AND
      METHODS: We conducted a prospective study with 40 pediatric patients scheduled
      for outpatient colonoscopy. Patients were enrolled continuously and were
      randomized to receive CO2 or air insufflation. Patients and colonoscopists were
      blinded to insufflation method. End tidal CO2 (EtCO2) was documented throughout
      the procedure. Abdominal pain was established preprocedure then at 1-, 6-, and 24
      hour postprocedure. Subject demographics, indications, colonoscopists' year of
      training, time to cecum, adverse events, and final diagnoses were recorded.
      RESULTS: Twenty patients were randomized to each group. Patients receiving air
      had a statistically significant increase in pain from baseline at 1- and 6-hours
      after colonoscopy (P=0.007 and 0.008). This was not seen in the CO2 group
      (P=0.740 and 0.289). There was an increase in postprocedure pain in the air group
      compared with CO2 group at the 1-hour mark (P=0.032). EtCO2 increased during the
      procedure, regardless of insufflation method, but no difference was seen between
      groups (P=0.822). CONCLUSIONS: Our results demonstrate that higher levels of pain
      were reported by patients following air compared with those receiving CO2
      insufflation. This is the first study to show CO2 is as safe as air, with no
      increase in EtCO2 between groups in the pediatric population. CO2 is an effective
      and safe modality and should be considered for pediatric colonoscopies.

PMID- 29210904
TI  - Chondrosarcoma of the cervical spine.
AB  - This case report describes the diagnosis, surgical treatment, and management of a
      patient with low-grade chondrosarcoma of the cervical spine that initially
      presented as myositis ossificans. Chondrosarcoma is rare in the cervical spine
      and in this patient, may have been the result of an injury from a motor vehicle
      crash. The management of this patient has been unusual in that a complete
      excision was not performed because the patient refused standard treatment.

PMID- 29210905
TI  - Endoscopic transluminal debridement of the pancreas.
AB  - Most patients with acute pancreatitis will develop edematous pancreatitis with a
      mild course and spontaneous resolution within several days to a few weeks.
      However, about 20% of patients will develop necrotizing pancreatitis, which
      carries a high mortality. This case report focuses on a patient with infected
      necrosis of the pancreas, which is managed with endoscopic transluminal
      debridement, a safe alternative to open surgery.

PMID- 29210906
TI  - Temperature management for out-of-hospital cardiac arrest.
AB  - More than 300,000 Americans suffer a cardiac arrest outside of the hospital each
      year and even among those who are successfully resuscitated and survive to
      hospital admission, outcomes remain poor. Temperature management (previously
      known as therapeutic hypothermia) is the only intervention that has been
      reproducibly demonstrated to ameliorate the neurologic injury that follows
      cardiac arrest. The results of a recent large randomized controlled trial have
      highlighted the uncertainty about temperature management strategies following
      cardiac arrest. This article reviews the issues and recommendations.

PMID- 29210907
TI  - Musculoskeletal development in patients with Down syndrome.
AB  - Down syndrome is a chromosomal aneuploidy that results in disruptions in multiple
      body systems, including musculoskeletal function. Early intervention to focus on
      bone mineral density, gait correction, agility, balance, and muscle strength is
      imperative in order for patients to achieve maximum potential.

PMID- 29210908
TI  - Does using PAs in the closed treatment of pediatric forearm fractures increase
      malunion risk?
AB  - PURPOSE: This study assessed whether using physician assistants (PAs) for
      fracture follow-up during nonoperative management of pediatric forearm fractures
      was associated with an increased risk of malunion. METHODS: The study was a
      retrospective review of charts of 141 children under age 18 years who were
      treated nonoperatively in the division of orthopedics over 12 months for forearm
      fractures. The effect of type and number of follow-up providers on risk of
      malunion was determined and controlled for fracture type, location, and initial
      angulation. Logistic regression, Fisher exact test, and Cochran-Armitage trend
      test were used to analyze the data, with P < .05 indicating statistical
      significance. RESULTS: Using strict criteria, malunion was identified in 42 (30%)
      of 141 patients. Follow-up provided by even up to four PAs did not increase
      malunion risk. Transfer of care between two attending physicians increased
      malunion risk, independent of fracture characteristics. CONCLUSION: The
      involvement of even multiple PAs during follow-up management of nonoperatively
      treated pediatric forearm fractures is not associated with an increase in the
      risk of malunion. These findings are consistent with previous published works
      that highlighted the safe and valuable role PAs can play in the management of
      common fractures.

PMID- 29210909
TI  - Tetanus.

PMID- 29210910
TI  - Five easy-to-master uses for point-of-care ultrasound.
AB  - Clinicians are increasingly becoming familiar with the value of limited, focused
      point-of-care ultrasonography (POCUS) to help answer discrete clinical questions.
      Ultrasound education is being taught in medical schools and physician assistant
      (PA) and PA postgraduate programs nationwide. This article introduces five basic
      POC ultrasound scans that can easily be mastered by practicing PAs.

PMID- 29210912
TI  - An uncommon complication of a foot fracture.

PMID- 29210913
TI  - Weekend call: Sifting the salient points.

PMID- 29210914
TI  - Poster session highlights PA research.

PMID- 29210915
TI  - "It's just a virus".

PMID- 29210916
TI  - Acute Inflammatory Responses to Exercise in Patients with Abdominal Aortic
      Aneurysm.
AB  - PURPOSE: Inflammation and extracellular matrix degeneration contribute to
      abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of
      exercise intensity on circulating biomarkers of inflammation and extracellular
      matrix degeneration in patients with AAA and healthy older adults. METHODS:
      Twenty patients with AAA (74 +/- 6 yr) and 20 healthy males (72 +/- 5 yr)
      completed moderate-intensity cycling at 40% peak power output, higher-intensity
      intervals at 70% peak power output, and control (rest) on separate days.
      Circulating matrix metalloproteinase-9 (MMP-9), transforming growth factor beta
      1, interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-alpha) were
      analyzed at rest and 0 to 90 min postexercise. RESULTS: Biomarkers at baseline
      were similar between groups. IL-6 responses to exercise were similar between
      groups, with a greater increase in DeltaIL-6 after moderate-intensity compared
      with higher-intensity exercise (P < 0.001). Delta MMP-9 showed a 118-ng.mL (95%
      confidence interval = 23 to 214, P = 0.02) greater increase immediately after
      higher-intensity exercise compared with changes in control in both groups. Delta
      MMP-9 then decreased by 114 ng.mL (18 to 211, P = 0.02) 90 min after higher
      intensity exercise compared with the changes in control. Delta TNF-alpha was not
      different between protocols in healthy adults. In patients with AAA, delta TNF
      alpha showed a greater decrease after higher-intensity compared with moderate
      intensity exercise (-6.1 pg.mL, -8.5 to -3.6, P < 0.001) and control (-4.9 pg.mL,
      -7.4 to -2.4, P < 0.001). IL-10 and transforming growth factor beta 1 did not
      change in either group. CONCLUSIONS: These findings suggest that a bout of higher
      intensity exercise elicits a greater anti-inflammatory response compared with
      moderate-intensity exercise, which may be further augmented in patients with AAA.
      Exercise-induced reductions in biomarkers associated with AAA progression may
      represent a protective effect of exercise in patients with AAA.

PMID- 29210917
TI  - Link between Physical Activity Type in Adolescence and Body Composition in
      Adulthood.
AB  - PURPOSE: We investigated whether type of physical activity (PA) (sports, running,
      and fitness/dance) engaged in during adolescence is associated with body
      composition in late adolescence or early adulthood. METHODS: Data were drawn from
      631 participants in the Nicotine Dependence in Teens study, a prospective
      investigation of students ages 12-13 yr at inception. Self-report PA data were
      collected at baseline, in grade 7, and every 3-4 months thereafter during the 5
      yr of high school (1999-2005). Anthropometric indicators (height, weight, waist
      circumference, triceps, and subscapular skinfold thickness) were measured at ages
      12, 16, and 24 yr. On the basis of prior exploratory factor analysis, PA was
      categorized into one of three types (sports, running, and fitness/dance).
      Regression models estimated the association between number of years participating
      in each PA type (0-5 yr) during high school and body composition measures in
      later adolescence or early adulthood. RESULTS: In multivariable models accounting
      for age, sex, and parent education, more number of years participating in running
      during adolescence was associated with lower body mass index, waist
      circumference, and skinfold thickness in later adolescence and early adulthood
      (all P < 0.01). This association was no longer apparent in models that accounted
      for body composition at age 12 yr. The number of years participating in sports
      was positively associated with body mass index in early adulthood (P = 0.02), but
      fitness/dance was not statistically significantly associated with any outcome.
      CONCLUSION: Sustaining participation in running, but not in other PA types,
      during adolescence was related to lower body composition in later adolescence and
      adulthood. However, more research is needed to determine whether this association
      is attributable to a relationship between PA and body composition in early
      adolescence.

PMID- 29210918
TI  - Association between Physical Activity and Adiposity in Adolescents with Down
      Syndrome.
AB  - PURPOSE: Obesity is highly prevalent among adolescents with Down syndrome (DS);
      however, reported associations between body composition and moderate-to-vigorous
      physical activity (MVPA) have been small and nonsignificant. The purpose of this
      study was to compare group differences between adolescents with and without DS,
      including dual-energy x-ray absorptiometry (DXA) measured body composition and
      accelerometer-measured physical activity, and then examine associations within
      adolescents with DS. METHODS: Thirty-nine adolescents (22 with DS and 17
      typically developing controls) 12-18 yr of age participated in the study. Groups
      had similar distributions of age, sex, and Tanner pubertal stage. Body
      composition was assessed by DXA, body mass index (BMI), and BMI percentile. MVPA
      was measured with ActiGraph GT3X+ accelerometers. RESULTS: Adolescents with DS
      had significantly higher BMI, BMI percentile, and DXA-derived percent body fat
      (%BF) as well as lower MVPA compared with controls (P < 0.05). Associations
      between MVPA and %BF in adolescents with DS were moderate (r = -0.39, P = 0.07)
      but substantially stronger than BMI (r = -0.19, P = 0.40). However, linear
      regression analyses identified Tanner stage (beta = -0.77, P < 0.001) and MVPA
      (beta = -0.34, P = 0.047) as significant predictors of %BF. No relevant
      associations between body composition and MVPA were observed in adolescents with
      typical development (P > 0.05). CONCLUSIONS: Our findings suggest that MVPA is
      associated with adiposity when measured with DXA among adolescents with DS.

PMID- 29210919
TI  - The Role of Combination Therapy in Pediatric Inflammatory Bowel Disease: A
      Clinical Report from the North American Society for Pediatric Gastroenterology,
      Hepatology and Nutrition.
AB  - The treatment goal for children suffering from inflammatory bowel disease has
      been evolving with biologic therapies like anti-tumor necrosis factor agents
      assuming a more central role in treatment of more aggressive and extensive
      phenotype. Earlier introduction of anti-tumor necrosis factor agents have shown
      to be more effective and may even alter the natural history of inflammatory bowel
      disease. Development of anti-drug antibodies, however, limits long-term usage and
      leads to dose adjustment in almost half of patients treated with these
      medications. One of the strategies to minimize the development of anti-drug
      antibodies has been concomitant use of immunomodulator medications, resulting in
      fewer infusion reactions and sustained trough levels, potentially lowering the
      need for dose adjustments. Balanced with these benefits of optimized dosing and
      likely more sustained response, however, is the concern about increased risk of
      complications, such as infections and malignancies. The current manuscript
      reviews the available pediatric literature regarding efficacy, safety, and side
      effect profile of combination (immunomodulator and biologics) therapy in
      pediatric Crohn disease and ulcerative colitis, with particular emphasis on cost
      constraints, and recommendations for selection of patients who would benefit most
      from combination therapy.

PMID- 29210920
TI  - Safety of Appetite Manipulation in Children with Feeding Disorders Admitted to an
      Inpatient Feeding Program.
AB  - OBJECTIVE: Appetite manipulation can be effective in weaning children off
      gastrostomy tube feeding dependence but can cause dehydration, hypoglycaemia, and
      ketone body production, which is anorexigenic. As the safety of this approach has
      not been described, our aim was to describe adverse events observed when weaning
      children from G-tube dependence using our appetite manipulation protocol.
      METHODS: This was a retrospective study of prospectively collected data of
      patients who completed our inpatient tube-weaning protocol. Daily safety
      parameters included twice-daily urine specific gravities and urine ketones and
      fasting capillary blood glucose. Graded clinical interventions to manage adverse
      events were collected. RESULTS: A total of 143 children with a mean age of 4.8 +/
      2.4 years were seen in the inpatient feeding program of which 74 (51.7%) were
      male. The children were hospitalized 10.1 +/- 2.5 days with the vast majority
      being discharged between days 11 and 14. Overall, 78.2% of patients experienced
      at least 1 adverse event: urine specific gravity >1.020 was seen in 60.5%,
      ketonuria in 48.9%, and hypoglycemia (<=60 mg/dL) in 13.4%. Only 2 children had
      blood glucose levels <40 mg/dL and these were corrected with oral
      supplementation. Graded clinical interventions to manage adverse events included
      oral rehydration in 89.9% of children and supplemental tube feeding in 25.2%.
      CONCLUSIONS: Adverse effects are common when appetite manipulation is used to
      wean children off G-tube dependence. Anticipating, monitoring, and having a clear
      intervention plan in a closely monitored setting are necessary to safely use this
      method.

PMID- 29210921
TI  - Celiac Disease by the Age of 13 Years Is Not Associated With Probiotics
      Administration in Infancy.
AB  - Probiotics are theoretically promising in primary prevention of celiac disease
      (CD), but research evidence on the topic is scarce. We used the data and material
      of a clinical double-blind randomized placebo-controlled trial on primary allergy
      prevention (n = 1223) to investigate in an exploratory study whether
      administration of a mix of pro- and prebiotics during late pregnancy and first 6
      months of life was associated with prevalence of CD during 13-year follow-up.
      Children who fulfilled diagnostic criteria for CD (n = 11) and subjects with a
      serum sample available for analyzing CD antibodies (n = 867) were included. CD or
      elevated tissue transglutaminase IgA antibodies were not associated with
      probiotics or placebo. Nor were there any associations with the mode of delivery,
      the duration of exclusive or total breast-feeding, or respiratory infections
      during the first 2 years of life. Allergic diseases or sensitization by the age
      of 2 or 5 years were not clearly associated with the development of CD.

PMID- 29210922
TI  - Splenda in the Milk: Hitting the Sweet Spot.

PMID- 29210923
TI  - Faecal Calprotectin: What Does This Mean for the Paediatric Inflammatory Bowel
      Disease Phenotype?

PMID- 29210924
TI  - Intraventricular Hemorrhage in Moderate to Severe Congenital Heart Disease.
AB  - OBJECTIVES: Determine the prevalence of intraventricular hemorrhage in infants
      with moderate to severe congenital heart disease, investigate the impact of
      gestational age, cardiac diagnosis, and cardiac intervention on intraventricular
      hemorrhage, and compare intraventricular hemorrhage rates in preterm infants with
      and without congenital heart disease. DESIGN: A single-center retrospective
      review. SETTING: A tertiary care children's hospital. PATIENTS: All infants
      admitted to St. Louis Children's Hospital from 2007 to 2012 with moderate to
      severe congenital heart disease requiring cardiac intervention in the first 90
      days of life and all preterm infants without congenital heart disease or
      congenital anomalies/known genetic diagnoses admitted during the same time
      period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cranial ultrasound
      data were reviewed for presence/severity of intraventricular hemorrhage. Head CT
      and brain MRI data were also reviewed in the congenital heart disease infants.
      Univariate analyses were undertaken to determine associations with
      intraventricular hemorrhage, and a final multivariate logistic regression model
      was performed. There were 339 infants with congenital heart disease who met
      inclusion criteria and 25.4% were born preterm. Intraventricular hemorrhage was
      identified on cranial ultrasound in 13.3% of infants, with the majority of
      intraventricular hemorrhage being low-grade (grade I/II). The incidence increased
      as gestational age decreased such that intraventricular hemorrhage was present in
      8.7% of term infants, 19.2% of late preterm infants, 26.3% of moderately preterm
      infants, and 53.3% of very preterm infants. There was no difference in
      intraventricular hemorrhage rates between cardiac diagnoses. Additionally, the
      rate of intraventricular hemorrhage did not increase after cardiac intervention,
      with only three infants demonstrating new/worsening high-grade (grade III/IV)
      intraventricular hemorrhage after surgery. In a multivariate model, only
      gestational age at birth and African-American race were predictors of
      intraventricular hemorrhage. In the subset of infants with CT/MRI data, there was
      good sensitivity and specificity of cranial ultrasound for presence of
      intraventricular hemorrhage. CONCLUSIONS: Infants with congenital heart disease
      commonly develop intraventricular hemorrhage, particularly when born preterm.
      However, the vast majority of intraventricular hemorrhage is low-grade and is
      associated with gestational age and African-American race.

PMID- 29210925
TI  - Frequency of Desaturation and Association With Hemodynamic Adverse Events During
      Tracheal Intubations in PICUs.
AB  - OBJECTIVES: Oxygen desaturation during tracheal intubation is known to be
      associated with adverse ICU outcomes in critically ill children. We aimed to
      determine the occurrence and severity of desaturation during tracheal intubations
      and the association with adverse hemodynamic tracheal intubation-associated
      events. DESIGN: Retrospective cohort study as a part of the National Emergency
      Airway Registry for Children Network's quality improvement project from January
      2012 to December 2014. SETTING: International PICUs. PATIENTS: Critically ill
      children younger than 18 years undergoing primary tracheal intubations in the
      ICUs. INTERVENTIONS: tracheal intubation processes of care and outcomes were
      prospectively collected using standardized operational definitions. We defined
      moderate desaturation as oxygen saturation less than 80% and severe desaturation
      as oxygen saturation less than 70% during tracheal intubation procedures in
      children with initial oxygen saturation greater than 90% after preoxygenation.
      Adverse hemodynamic tracheal intubation-associated event was defined as cardiac
      arrests, hypo or hypertension requiring intervention, and dysrhythmia.
      MEASUREMENTS AND MAIN RESULTS: A total of 5,498 primary tracheal intubations from
      31 ICUs were reported. Moderate desaturation was observed in 19.3% associated
      with adverse hemodynamic tracheal intubation-associated events (9.8% among
      children with moderate desaturation vs 4.4% without desaturation; p < 0.001).
      Severe desaturation was observed in 12.9% of tracheal intubations, also
      significantly associated with hemodynamic tracheal intubation-associated events.
      After adjusting for patient, provider, and practice factors, the occurrence of
      moderate desaturation was independently associated with hemodynamic tracheal
      intubation-associated events: adjusted odds ratio 1.83 (95% CI, 1.34-2.51; p <
      0.001). The occurrence of severe desaturation was also independently associated
      with hemodynamic tracheal intubation-associated events: adjusted odds ratio 2.16
      (95% CI, 1.54-3.04; p < 0.001). Number of tracheal intubation attempts was also
      significantly associated with the frequency of moderate and severe desaturations
      (p < 0.001). CONCLUSIONS: In this large tracheal intubation quality improvement
      database, we found moderate and severe desaturation are reported among 19% and
      13% of all tracheal intubation encounters. Moderate and severe desaturations were
      independently associated with the occurrence of adverse hemodynamic events.
      Future quality improvement interventions may focus to reduce desaturation events.

PMID- 29210926
TI  - Hospital Readmissions After Pediatric Trauma.
AB  - OBJECTIVES: To determine the rate, etiology, and timing of unplanned and planned
      hospital readmissions and to identify risk factors for unplanned readmission in
      children who survive a hospitalization for trauma. DESIGN: Multicenter
      retrospective cohort study of a probabilistically linked dataset from the
      National Trauma Data Bank and the Pediatric Health Information System database,
      2007-2012. SETTING: Twenty-nine U.S. children's hospitals. PATIENTS: 51,591
      children (< 18 yr at admission) who survived more than or equal to a 2-day
      hospitalization for trauma. MEASUREMENTS AND MAIN RESULTS: The primary outcome
      was unplanned readmission within 1 year of discharge from the injury
      hospitalization. Secondary outcomes included any readmission, reason for
      readmission, time to readmission, and number of readmissions within 1 year of
      discharge. The primary exposure groups were isolated traumatic brain injury, both
      traumatic brain injury and other injury, or nontraumatic brain injury only. We
      hypothesized a priori that any traumatic brain injury would be associated with
      both planned and unplanned hospital readmission. We used All Patient Refined
      Diagnosis Related Groups codes to categorize readmissions by etiology and planned
      or unplanned. Overall, 4,301/49,982 of the patients (8.6%) with more than or
      equal to 1 year of observation time were readmitted to the same hospital within 1
      year. Many readmissions were unplanned: 2,704/49,982 (5.4%) experienced an
      unplanned readmission in the first year. The most common reason for unplanned
      readmission was infection (22%), primarily postoperative or posttraumatic
      infection (38% of readmissions for infection). Traumatic brain injury was
      associated with lower odds of unplanned readmission in multivariable analyses.
      Seizure or RBC transfusion during the index hospitalization were the strongest
      predictors of unplanned, earlier, and multiple readmissions. CONCLUSIONS: Many
      survivors of pediatric trauma experience unplanned, and potentially preventable,
      hospital readmissions in the year after discharge. Identification of those at
      highest risk of readmission can guide targeted in-hospital or postdischarge
      interventions.

PMID- 29210927
TI  - Pediatric Critical Care Medicine Training: 2004-2016.
AB  - OBJECTIVES: To describe growth trends in the number of programs, positions, and
      applicants in pediatric critical care medicine fellowship training as part of the
      Pediatric Critical Care Medicine Training Study. DESIGN: Descriptive study.
      SETTINGS: Available archived Match data through the National Resident Matching
      Program and training data from the Accreditation Council for Graduate Medical
      Education. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      analyzed all data on programs, positions, and applicants through the National
      Resident Matching Program Specialties Matching Service during the study period of
      2004 to 2016. We also analyzed available training data available through the
      Accreditation Council for Graduate Medical Education for the corresponding study
      period. During the 12-year study period, there was a statistically significant
      expansion in programs (38%), positions (82%), and applicants (151%).
      Correspondingly, the percentage of pediatric critical care medicine programs
      participating in the Match as a percentage of all Accreditation Council for
      Graduate Medical Education-accredited programs for that academic year increased
      24%. As of 2015, 94% of total first year positions offered for pediatric critical
      care medicine were through the Match. CONCLUSIONS: For the period 2004 to 2016,
      there was a substantial increase in positions and applicants applying for
      training in pediatric critical care medicine. We document an increase in demand
      (i.e., applicants) that has been matched by an increase in supply (i.e.,
      positions) for pediatric critical care medicine fellowship training. The nearly
      complete use of the National Resident Matching Program for placing applicants in
      training positions in pediatric critical care medicine suggests that these data
      can be used to inform workforce analysis in pediatric critical care medicine.

PMID- 29210928
TI  - Retinal Ganglion Cell Topography in Patients With Visual Pathway Pathology.
AB  - BACKGROUND: To investigate and quantify the impact of intracranial lesions at
      different locations within the visual pathway on the ganglion cell layer-inner
      plexiform layer (GCL-IPL) complex and the retinal nerve fiber layer (RNFL).
      METHODS: Patients with intracranial lesions affecting the optic chiasm (Group I)
      or the optic tract and/or lateral geniculate nucleus (Group II) were included.
      All patients received kinetic visual field assessment and underwent spectral
      domain optical coherence tomography. Peripapillary and papillomacular bundle
      (PMB) RNFL and macular GCL-IPL thickness in 4 perifoveal areas were measured and
      compared with normal values derived from 52 age-matched healthy control subjects.
      Z-scores for each parameter of every patient were calculated and compared with
      the normative data. Z-scores less than -2.0 (e.g., -2.5) were considered as being
      statistically significant. RESULTS: Twenty-two patients (Group I and II: 13 and
      9, respectively) were included. Ten of 13 patients in Group I showed significant
      binasal GCL-IPL thinning, with associated temporal sector thinning in 8 patients.
      In Group II, all 9 patients showed significant reduction of the GCL-IPL
      corresponding to the homonymous visual field defect, but only 4 demonstrated RNFL
      thinning. Contralateral RNFL thinning within the PMB clinically similar to bow
      tie atrophy was evident in all patients in Group II. GCL-IPL and RNFL thinning
      varied in severity from mild (isolated PMB RNFL thickness reduction) to severe
      (bilateral asymmetrical reduction of PMB RNFL associated with asymmetric,
      predominantly nasal reduction of GCL-IPL) in Group I. CONCLUSION: Clinical
      abnormalities in patients with visual pathway lesions are more likely to
      demonstrate abnormalities of GCL-IPL than global peripapillary RNFL thickness.
      However, PMB thickness measurement appears to be a valuable tool to detect
      abnormalities of the anterior visual pathways. If peripapillary RNFL measurements
      are performed in such patients, PMB thickness should be considered the most
      useful quantitative parameter.

PMID- 29210929
TI  - Optic Disc Edema in Glial Fibrillary Acidic Protein Autoantibody-Positive
      Meningoencephalitis.
AB  - BACKGROUND: Glial fibrillary acidic protein (GFAP) autoantibody-positive
      meningoencephalitis is a newly described entity characterized by a corticosteroid
      responsive meningoencephalomyelitis. Some patients with GFAP autoantibody
      positive meningoencephalitis have been found to have optic disc edema, which has
      previously not been well characterized. METHODS: We performed a retrospective,
      observational case series of Mayo Clinic patients found to have GFAP-IgG and
      optic disc edema from January 1, 2000, to December 31, 2016. We identified 40
      patients with GFAP-IgG seropositivity by tissue-based immunofluorescence and cell
      based assay. Patients were screened for the following inclusion criteria: 1)
      serum, cerebrospinal fluid, or both that yielded a characteristic astrocytic
      pattern of mouse tissue immunostaining with confirmation of IgG reactive with
      specific GFAPalpha isoform by cell-based assay; 2) meningoencephalitis or
      encephalitis; and 3) optic disc edema. We excluded those with coexisting
      aquaporin-4-IgG or insufficient clinical information. RESULTS: Ten patients had
      optic disc edema and met inclusion criteria. The median age was 39.5 years and
      60% were men. Visual acuity was unaffected and disc edema was bilateral in all
      cases. Mild vitreous cell was noted in 3 patients. The optic disc edema resolved
      with corticosteroid treatment but resulted in mild optic atrophy in 2 patients.
      The median lumbar puncture opening pressure was 144 mm H2O (range, 84-298 mm
      H2O). Brain MRI revealed radial perivascular enhancement in all except 1 patient.
      Fluorescein angiography was available for 1 patient with optic disc edema, which
      showed leakage from the venules. CONCLUSIONS: Patients with GFAP autoantibody
      positive meningoencephalitis can have optic disc edema that can mimic
      papilledema. The cause of the optic disc edema remains uncertain, but most
      patients did not have raised intracranial pressure.

PMID- 29210930
TI  - Leber Hereditary Optic Neuropathy Caused by a Mitochondrial DNA 10663T>C Point
      Mutation and Its Response to Idebenone Treatment.

PMID- 29210931
TI  - Phase Angle Is Moderately Associated With Muscle Quality and Functional Capacity,
      Independent of Age and Body Composition in Older Women.
AB  - BACKGROUND AND PURPOSE: There is a growing body of evidence indicating that phase
      angle (PhA) can be used as an indicator of nutritional status, disease prognosis,
      and mortality risk; however, it is still unknown whether PhA can be used as an
      explanator of functional capacity and muscle quality in older women. The main
      purpose of this cross-sectional study was to explore whether PhA is associated
      with muscle quality and functional capacity in older women, regardless of total
      and regional body composition. METHODS: A total of 125 older women-66.7 (4.7)
      years; 65.6 (10.9) kg body mass; 156.1 (5.2) cm height; 26.9 (4.0) kg/m body mass
      index-participated in this study. Anthropometric, PhA, body composition (whole
      body dual-energy x-ray absorptiometry) and muscle quality (defined as total
      muscular strength per kilogram of appendicular lean soft tissue) were measured.
      The functional capacity was assessed by 4 tests: 10-m walk test, rising from
      sitting position, rising from ventral decubitus position, and rising from a chair
      and walking around the house. The summing z-scores for the 4 tests was used as a
      continuous functional capacity score. Linear regression analysis was conducted to
      test whether PhA is related to the dependent variables (muscle quality and
      functional capacity), after adjusting for potential covariates. RESULTS: The PhA
      presented a small-to-moderate relationship with muscle quality (r = 0.27; P <
      .01) and functional capacity (r = 0.31; P < .01), respectively. These
      relationships remained significant after adjustment for age, lower limb lean soft
      tissue, and total fat mass for muscle quality (beta = 0.55; P < .01) and
      functional capacity (beta = 1.38; P < .01). CONCLUSION: Our findings suggest that
      healthy elderly women with higher values of PhA have a better muscle quality and
      functionality, regardless of age and body composition.

PMID- 29210932
TI  - Score Distributions of the Balance Outcome Measure for Elder Rehabilitation
      (BOOMER) in Community-Dwelling Older Adults With Vertebral Fracture.
AB  - BACKGROUND AND PURPOSE: We sought to evaluate the Balance Outcome Measure for
      Elder Rehabilitation (BOOMER) in community-dwelling women 65 years and older with
      vertebral fracture and to describe score distributions and potential ceiling and
      floor effects. METHODS: This was a secondary data analysis of baseline data from
      the Build Better Bones with Exercise randomized controlled trial using the
      BOOMER. A total of 141 women with osteoporosis and radiographically confirmed
      vertebral fracture were included. Concurrent validity and internal consistency
      were assessed in comparison to the Short Physical Performance Battery (SPPB).
      Normality and ceiling/floor effects of total BOOMER scores and component test
      items were also assessed. Exploratory analyses of assistive aid use and falls
      history were performed. RESULTS AND DISCUSSION: Tests for concurrent validity
      demonstrated moderate correlation between total BOOMER and SPPB scores. The
      BOOMER component tests showed modest internal consistency. Substantial ceiling
      effect and nonnormal score distributions were present among overall sample and
      those not using assistive aids for total BOOMER scores, although scores were
      normally distributed for those using assistive aids. The static standing with
      eyes closed test demonstrated the greatest ceiling effects of the component
      tests, with 92% of participants achieving a maximal score. CONCLUSIONS: While the
      BOOMER compares well with the SPPB in community-dwelling women with vertebral
      fractures, researchers or clinicians considering using the BOOMER in similar or
      higher-functioning populations should be aware of the potential for ceiling
      effects.

PMID- 29210933
TI  - Two-Minute Step Test of Exercise Capacity: Systematic Review of Procedures,
      Performance, and Clinimetric Properties.
AB  - BACKGROUND AND PURPOSE: The 2-minute step test (TMST) is one of many alternatives
      for measuring exercise capacity. First introduced in 1999 as part of the Senior
      Fitness Test, the TMST has the advantage of requiring limited space, only a few
      minutes' time, and no expensive equipment. These advantages notwithstanding, the
      test must be clinimetrically sound if it is to be recommended. We sought
      therefore to summarize the literature addressing TMST performance and measurement
      properties. METHODS: Relevant literature was identified by searches of 3
      electronic databases (PubMed, Scopus, and Cumulative Index of Nursing and Allied
      Health) and hand searches. Inclusion of an article required that it described use
      of the TMST of Rikli and Jones and that it focused on adults. Articles published
      in a language other than English were excluded. Studies were abstracted for
      information on participants, TMST description, and findings. RESULTS AND
      DISCUSSION: Thirty articles were deemed appropriate based on inclusion and
      exclusion criteria. The participants in the studies included community-dwelling
      healthy older adults and adults with assorted pathologies. Studies described
      varied methods of conducting the TMST. Among tests in which steps for one side
      were counted over a full 2 minutes, the mean number of steps among populations
      ranged from 29.1 for patients with chronic stroke to 110.8 for older osteoporotic
      women. Numerous reviewed studies provide support for the validity of the TMST.
      Only one study addressed reliability and none focused on responsiveness.
      Normative data have been proffered. CONCLUSIONS: The TMST has been widely used
      since first introduced, albeit not always as originally described. There is
      considerable evidence for the validity of the test, but its reliability and
      responsiveness are not yet firmly established.

PMID- 29210934
TI  - A Scoping Review of Physical Performance Outcome Measures Used in Exercise
      Interventions for Older Adults With Alzheimer Disease and Related Dementias.
AB  - BACKGROUND AND PURPOSE: There is growing evidence that exercise interventions can
      mitigate functional decline and reduce fall risk in older adults with Alzheimer
      disease and related dementias (ADRD). Although physical performance outcome
      measures have been successfully used in older adults without cognitive
      impairment, additional research is needed regarding their use with individuals
      who have ADRD, and who may have difficulty following instructions regarding
      performance of these measures. The purpose of this scoping review was to identify
      commonly used physical performance outcome measures, for exercise interventions,
      that are responsive and reliable in older adults with ADRD. Ultimately, we aimed
      to provide recommendations regarding the use of outcome measures for individuals
      with ADRD across several domains of physical performance. METHODS: A scoping
      review was conducted to broadly assess physical performance outcome measures used
      in exercise interventions for older adults with ADRD. Exercise intervention
      studies that included at least 1 measure of physical performance were included.
      All physical performance outcome measures were abstracted, coded, and categorized
      into 5 domains of physical performance: fitness, functional mobility, gait,
      balance, and strength. Criteria for recommendations were based on (1) the
      frequency of use, (2) responsiveness, and (3) reliability. Frequency was
      determined by the number of studies that used the outcome measure per physical
      performance domain. Responsiveness was assessed via calculated effect size of the
      outcome measures across studies within physical performance domains. Reliability
      was evaluated via published studies of psychometric properties. RESULTS AND
      DISCUSSION: A total of 20 physical performance outcome measures were extracted
      from 48 articles that met study inclusion criteria. The most frequently used
      outcome measures were the 6-minute walk test, Timed Up and Go, repeated chair
      stand tests, short-distance gait speed, the Berg Balance Scale, and isometric
      strength measures. These outcome measures demonstrated a small, medium, or large
      effect in at least 50% of the exercise intervention studies. Good to excellent
      reliability was reported in samples of older adults with mild to moderate
      dementia. Fitness, functional mobility, gait, balance, and strength represent
      important domains of physical performance for older adults. The 6-minute walk
      test, Timed Up and Go, repeated chair stand tests, short-distance gait speed,
      Berg Balance Scale, and isometric strength are recommended as commonly used and
      reliable physical performance outcome measures for exercise interventions in
      older adults with mild to moderate ADRD. Further research is needed on optimal
      measures for individuals with severe ADRD. CONCLUSIONS: The results of this
      review will aid clinicians and researchers in selecting reliable measures to
      evaluate physical performance outcomes in response to exercise interventions in
      older adults with ADRD.

PMID- 29210935
TI  - Performance of Different Timed Up and Go Subtasks in Frailty Syndrome.
AB  - BACKGROUND AND PURPOSE: Gait speed, mobility, and postural transitions should be
      taken into account in older adults with frailty syndrome and can be assessed by
      the Timed Up and Go (TUG) Test. However, it is unclear which TUG subtasks have
      greater influence in identifying frail people and whether prefrail individuals
      present with any reduced subtask performance. The objective of this study was to
      investigate the differences in performance of TUG subtasks between frail,
      prefrail, and nonfrail older adults. METHODS: A cross-sectional study was
      performed with community-dwelling older adults, including 43 nonfrail, 30
      prefrail, and 7 frail individuals. The TUG subtasks (sit-to-stand, walking
      forward, turning, walking back, and turn-to-sit) were assessed using a Qualisys
      motion system. Data were captured by Qualisys Track Manager software and
      processed by Visual 3D software. The Matlab program was used to detect, separate,
      and analyze the TUG subtasks. Statistical significance was set at alpha = .05 and
      SigmaPlot software (11.0) was used. RESULTS AND DISCUSSION: The total time to
      complete the TUG was significantly longer among frail participants than among
      those who were prefrail and nonfrail. Statistically significant differences in
      temporal parameters in the turning, walking forward, and walking back subtasks
      between nonfrail/prefrail and frail older people were found. In addition, the
      transition TUG subtasks (average and peak velocities of the trunk) distinguished
      the frail group from the other groups, demonstrating altered quality of movement.
      CONCLUSIONS: The findings support the value of analyzing the TUG subtasks to
      improve understanding of mobility impairment in frailty syndrome.

PMID- 29210937
TI  - RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients
      (2,074 Eyes).
AB  - PURPOSE: To study the clinical presentation, treatment, and outcome of patients
      with retinoblastoma (RB) in India. METHODS: Retrospective study of 1,457 patients
      with RB (2,074 eyes). RESULTS: The mean age at presentation of RB was 29 months
      (median, 24 months; range, <1-370 months). There were 812 (56%) men and 645 (44%)
      women with unilateral presentation of RB in 57% (n = 834) and bilateral in 43% (n
      = 623). Familial RB was present in 4% (n = 55). The most common presenting
      complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%),
      strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors
      were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor
      extension at presentation. The most common modalities of primary treatment
      included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%).
      At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months),
      92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on
      Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%,
      and 89%, respectively. CONCLUSION: The most common presenting signs of RB in
      Asian Indian population are leukocoria and proptosis. With appropriate treatment,
      the survival rate is favorable at 92%.

PMID- 29210938
TI  - Intraoperative Optical Coherence Tomography Imaging of the Peripheral Vitreous
      and Retina.

PMID- 29210939
TI  - VASCULAR REMODELING OF CHOROIDAL NEOVASCULARIZATION AFTER ANTI-VASCULAR
      ENDOTHELIAL GROWTH FACTOR THERAPY VISUALIZED ON OPTICAL COHERENCE TOMOGRAPHY
      ANGIOGRAPHY.
AB  - PURPOSE: To describe the qualitative and quantitative changes in choroidal
      neovascularization (CNV) flow pattern after anti-vascular endothelial growth
      factor therapy, by optical coherence tomography angiography (OCTA). METHODS:
      Consecutive patients with neovascular age-related macular degeneration underwent
      multimodal imaging, including OCTA at initial examination and at last visit. High
      flow networks in the choriocapillaris segmentation of OCTA were qualitatively and
      quantitatively analyzed at baseline and at follow-up, to characterize vascular
      flow changes after anti-vascular endothelial growth factor treatment and to
      correlate these changes with final exudation signs on spectral domain optical
      coherence tomography. RESULTS: Seventeen eyes were included. Mean follow-up was
      of 11.7 +/- 3.3 months. Baseline images showed six medusa pattern (35.3%), four
      seafan pattern (23.5%), and seven indistinct network patterns (41.2%). Mean CNV
      area at baseline was 1.58 +/- 1.72 mm. Final OCTA images revealed a decrease in
      CNV total area of 21.6%. In 6/17 eyes, the baseline neovascular pattern was
      unchanged; these cases were associated with exudation at the final spectral
      domain optical coherence tomography examination (P = 0.034) and a decrease in CNV
      area of 34.1%. Conversely, in 11/17 eyes (64.7%), the initial pattern had changed
      to a pruned vascular tree pattern, with variable exudative status on spectral
      domain optical coherence tomography at the final visit and a decrease in total
      CNV area of 0.07%. CONCLUSION: The vascular flow remodeling induced by recurrent
      anti-vascular endothelial growth factor treatment can be assessed by OCTA.
      Optical coherence tomography angiography may help to accurately evaluate
      treatment response and to recognize patterns usually associated with recurrent
      exudative activity.

PMID- 29210936
TI  - OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION
      SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.
AB  - PURPOSE: Widespread adoption of optical coherence tomography has revolutionized
      the diagnosis and management of retinal disease. If the cellular and subcellular
      sources of reflectivity in optical coherence tomography can be identified, the
      value of this technology will be advanced even further toward precision medicine,
      mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal
      bands are created by the exquisite arrangement of photoreceptors, Muller cells,
      retinal pigment epithelium, and Bruch membrane. Because of massed effects of
      these axially compartmentalized and transversely aligned cells, reflectivity can
      be localized to the subcellular level. This review focuses on the second of the
      four bands, called ellipsoid zone in a consensus clinical lexicon, with the
      central thesis that mitochondria in photoreceptor inner segments are a major
      independent reflectivity source in this band, because of Mie scattering and
      waveguiding. METHODS: We review the evolution of Band 2 nomenclature in published
      literature and discuss the origins of imaging signals from photoreceptor
      mitochondria that could make these organelles visible in vivo. RESULTS: Our
      recent data pertain to outer retinal tubulation, a unique neurodegenerative and
      gliotic structure with a highly reflective border, prominent in late age-related
      macular degeneration. High-resolution histology and multimodal imaging of outer
      retinal tubulation together provide evidence that inner segment mitochondria
      undergoing fission and translocation toward the nucleus provide the reflectivity
      signal. CONCLUSION: Our data support adoption of the ellipsoid zone nomenclature.
      Identifying subcellular signal sources will newly inform clinical.

PMID- 29210940
TI  - INTERNAL LIMITING MEMBRANE PEELING IN MACULAR HOLE SURGERY; WHY, WHEN, AND HOW?
AB  - PURPOSE: To review the current rationale for internal limiting membrane (ILM)
      peeling in macular hole (MH) surgery and to discuss the evidence base behind why,
      when, and how surgeons peel the ILM. METHODS: Review of the current literature.
      RESULTS: Pars plana vitrectomy is an effective treatment for idiopathic MH, and
      peeling of the ILM has been shown to improve closure rates and to prevent
      postoperative reopening. However, some authors argue against ILM peeling because
      it results in a number of changes in retinal structure and function and may not
      be necessary in all cases. Furthermore, the extent of ILM peeling optimally
      performed and the most favorable techniques to remove the ILM are uncertain.
      Several technique variations including ILM flaps, ILM scraping, and foveal
      sparing ILM peeling have been described as alternatives to conventional peeling
      in specific clinical scenarios. CONCLUSION: Internal limiting membrane peeling
      improves MH closure rates but can have several consequences on retinal structure
      and function. Adjuvants to aid peeling, instrumentation, technique, and
      experience may all alter the outcome. Hole size and other variables are important
      in assessing the requirement for peeling and potentially its extent. A variety of
      evolving alternatives to conventional peeling may improve outcomes and need
      further study.

PMID- 29210941
TI  - COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT
      EPITHELIUM, AND CHOROID FREE GRAFTS.
AB  - PURPOSE: To evaluate the feasibility and initial functional and anatomical
      outcomes of transplanting a full-thickness free graft of choroid and retinal
      pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and
      atrophy associated with end-stage exudative age-related macular degeneration with
      and without a concurrent refractory macular hole. METHODS: During vitrectomy, an
      RPE-choroidal and neurosensory retinal free graft was harvested in nine eyes of
      nine patients. The RPE-choroidal and neurosensory retinal free graft was either
      placed subretinally (n = 5), intraretinally to cover the foveal area inside an
      iatrogenically induced macular hole over the RPE-choroidal graft (n = 3) or
      preretinally (n = 1) without a retinotomy wherein both free grafts were placed
      over the concurrent macular hole. Silicone oil endotamponade was used in all
      cases. RESULTS: Mean follow-up was 7 +/- 5.5 months (range 3-19). The mean
      preoperative visual acuity was ~count fingers (logarithm of the minimum angle of
      resolution = 2.11, range 2-3), which improved to ~20/800 (logarithm of the
      minimum angle of resolution 1.62 +/- 0.48, range 0.7-2, P = 0.04). Vision was
      stable in 5 eyes (55.6%) and improved in 4 eyes (44.4%). Reading ability improved
      in 5 eyes (55.6%). Postoperative complications were graft atrophy (n = 1),
      epiretinal membrane (n = 1), and dislocation of neurosensory retina-choroid-RPE
      free graft (n = 1). CONCLUSION: Combined autologous RPE-choroid and neurosensory
      retinal free graft is a potential surgical alternative in eyes with end-stage
      exudative age-related macular degeneration, including concurrent refractory
      macular hole.

PMID- 29210942
TI  - Auditory Related Resting State fMRI Functional Connectivity in Tinnitus Patients:
      Tinnitus Diagnosis Performance.
AB  - OBJECTIVE: The purpose of the present study was to investigate functional
      connectivity in tinnitus patients with and without hearing loss, and design the
      tinnitus diagnosis performance by resting state functional magnetic resonance
      imaging (rs-fMRI). SUBJECTS AND METHODS: Nineteen volunteers with normal hearing
      without tinnitus, 18 tinnitus patients with hearing loss, and 11 tinnitus
      patients without hearing loss were enrolled in this study. The subjects were
      evaluated with rs-fMRI, and region of interests (ROIs) based correlation analyses
      were performed using the CONN toolbox version 16 and SPM version 8. The
      correlation coefficients from individual level results were converted into beta
      values. RESULTS: With a beta threshold of more than 0.2, 91% of all possible
      connections between auditory-related ROIs (Heschl's gyrus, planum temporale,
      planum polare, operculum, insular cortex, superior temporal gyrus) in the control
      group remained intact, whereas 83 and 66% of such connections were present in the
      hearing loss and the normal-hearing tinnitus group. However, between non-auditory
      related ROIs, the rates of intact connections at a beta threshold of more than
      0.2 were 17% in the control group, and 16 and 15% in the tinnitus groups. When
      resting state fMRI positive is defined as less than 9% of all possible
      connections between auditory-related ROIs with a beta threshold of more than 0.7,
      the sensitivity and specificity of tinnitus diagnosis is 86 and 74%,
      respectively. CONCLUSIONS: The associations between auditory-related networks are
      weakened in tinnitus patients, even if they have normal hearing. It is possible
      that rs-fMRI can be a tool for objective examination of tinnitus, by focusing the
      auditory-related areas.

PMID- 29210943
TI  - Survey of the American Neurotology Society on Cochlear Implantation: Part 2,
      Surgical and Device-Related Practice Patterns.
AB  - OBJECTIVE: To examine surgical and device-related cochlear implant practice
      patterns across centers in the United States. METHODS: Cross-sectional survey of
      the American Neurotology Society (ANS). RESULTS: A total of 81 surveys were
      returned from ANS members who report regular involvement in cochlear implant
      care. Overall there was a broad distribution in age and clinical experience, with
      most respondents reporting Accreditation Council for Graduate Medical Education
      (ACGME) accreditation in neurotology and employment at an academic center. The
      annual volume of cochlear implant surgeries varied considerably across centers.
      Eighty percent of respondents report to offer all three Food and Drug
      Administration (FDA) approved device brands at their center.In cases where
      hearing preservation is not a goal, 56% of respondents prefer a perimodiolar
      electrode design, while 44% prefer a lateral wall electrode. With regard to
      insertion technique for scala tympani access, 64% prefer inserting through the
      round window (RW) membrane, 26% prefer an extended round window (ERW) approach,
      while only 10% prefer a cochleostomy. In cases where hearing preservation is a
      goal of surgery, 86% of respondents prefer a lateral wall electrode design, while
      only 14% prefer a perimodiolar electrode design. With regard to insertion
      technique, 86% prefer RW insertion, while only 9% prefer an ERW approach, and
      only 5% prefer a cochleostomy. Respondents who prefer RW electrode insertion more
      commonly use a lateral wall electrode, whereas those who prefer an ERW or
      cochleostomy approach more commonly use a periomodiolar electrode (p < 0.001).
      There was a statistically significant greater number of surgeons that prefer
      lateral wall electrodes (p < 0.001) and RW insertion (p < 0.001) for hearing
      preservation cases compared with non-hearing preservation cases. For implantation
      of a hypothetical patient with significant residual hearing, within the range of
      hybrid device candidacy, the great majority of surgeons prefer a conventional
      length electrode and only 29% prefer to implant a hybrid device.In cases where
      hearing preservation is a goal, the overwhelming majority of respondents (96%, n
      = 74) reported using at least one form of steroid application. Ninety-two percent
      (n = 71) used intraoperative intravenous steroids, 55% (n = 42) prescribed
      postoperative oral steroids, 44% (n = 34) bathed the middle ear with steroids
      during surgery, and 30% (n = 23) prescribed preoperative oral steroids.Together,
      65% of respondents use a variation of the tight subperiosteal pocket technique
      for internal device fixation, 19% prefer a bony well and trough with tie-downs,
      10% prefer a bony well and trough without tie-downs, and 5% prefer a screw
      fixation system. Of the 50 who prefer utilizing a subperiosteal pocket, 31 (62%)
      incorporate a bony trough and 19 (38%) perform a subperiosteal pocket alone
      without a bony trough. CONCLUSION: The results of this survey reflect the
      evolution in surgical and device-related preferences for cochlear implantation in
      the United States. An increasing number of surgeons prefer the RW approach for
      electrode insertion. When hearing preservation is not a goal, there is a near
      even preference for lateral wall and perimodiolar electrode designs; however, the
      great majority of surgeons prefer a lateral wall design when attempting to
      preserve residual acoustic hearing. Even in cases where substantial residual
      hearing exists, many surgeons prefer conventional length electrodes to hybrid
      designs. These changes reflect the prioritization of atraumatic surgery and
      parallel the development of thinner and more atraumatic electrodes.

PMID- 29210944
TI  - Stapes Release in Tympanosclerosis.
AB  - : Tympanosclerosis in the middle ear space is common in Ethiopia and often
      involves the ossicles and particularly the stapes. Ear operations in Ethiopia are
      relatively expensive in this country of limited medical resources and a low
      average living wage. In this setting, 2-stage operations using prostheses become
      prohibitively expensive. Therefore, the recommended 2-stage approach for tympanic
      membrane perforation with tympanosclerosis and stapes fixation is impractical for
      Ethiopia.We present a series of 67 patients who had a single stage tympanoplasty,
      removal of tympanosclerosis from the stapes suprastructure, and ossicular chain
      reconstruction using ossicular interposition. Crucial is the surgical technique
      employed for peeling the mound of tympanosclerotic plaque off of the stapes,
      which we term the stapes release. Controls were 67 patients with similar
      perforations and air-bone gap, but no tympanosclerosis. Most controls had
      ossciular discontinuity and were reconstructed with type III tympanoplasty.Air
      bone gap improved in both groups: 18 dB (11 dB standard deviation) in the stapes
      release group, and 23 dB (11 dB standard deviation) in the control group. Paired
      t test found these improvements in each group significant at p < 0.001. Among the
      preoperative subjects there were 40 with air-bone gap greater than 45 dB, and
      none less than 20 dB. Among the postoperative subjects, none had air-bone gap
      worse than 45 dB, while 25/67 (37%) stapes release and 44/67 (66%) controls had
      air-bone gap better than 20 dB. Three patients in each group failed to close
      their perforations completely (96% closure rate).The only complications were two
      early cases of transient facial nerve weakness, which was avoided in subsequent
      cases by an alteration in technique. There was no deterioration of sensorineural
      hearing levels in either group's subjects postoperatively.In conclusion, stapes
      release with ossicular interposition can be performed at the same time as
      tympanoplasty without exacerbation of sensorineural hearing loss. Tympanic
      membrane closure and hearing levels were similar between patients with and
      without stapes fixation from tympanosclerosis.

PMID- 29210945
TI  - RE.: THE PAPER "IMPACT OF COCHLEAR IMPLANTATION ON COGNITIVE FUNCTIONS OF OLDER
      ADULTS: PILOT TEST RESULTS," RECENTLY PUBLISHED IN OTOLOGY & NEUROTOLOGY (38:E289
      E295_2017).

PMID- 29210946
TI  - Transcanal Endoscopic Ear Surgery to Treat Middle-Ear Cholesteatoma Should be
      Performed Cautiously.

PMID- 29210947
TI  - Toward Optimizing Cervical Vestibular Evoked Myogenic Potentials (cVEMP):
      Combining Air-Bone Gap and cVEMP Thresholds to Improve Diagnosis of Superior
      Canal Dehiscence.
AB  - OBJECTIVE: To develop a novel approach combining low-frequency air-bone gap (ABG)
      and cervical vestibular evoked myogenic potential (cVEMP) thresholds to improve
      screening for superior canal dehiscence (SCD) syndrome. STUDY DESIGN:
      Retrospective study. SETTING: Tertiary care center. PATIENTS: One hundred forty
      patients with SCD and 21 healthy age-matched controls were included. Ears for
      each patient were divided into three groups based on computed tomography (CT)
      findings: 1) dehiscent, 2) thin, or 3) unaffected. MAIN OUTCOME MEASURES: cVEMP
      and audiometric thresholds were analyzed and differences among groups were
      evaluated. RESULTS: We define the third window indicator (TWI) as the cVEMP
      thresholds at 500, 750, and 1000 Hz adjusted for the ABG at 250 Hz (i.e.,
      subtracting ABG from cVEMP threshold). The TWI differentiates between dehiscent
      and nondehiscent control ears with a sensitivity of 82% and specificity of 100%,
      corresponding to a positive predictive value of 100%. ABGs and cVEMP thresholds
      were similar for healthy controls and patients with thin bone over the superior
      canal. CONCLUSION: This is the largest study to date examining the usefulness of
      cVEMPs in the diagnosis of SCD. Our "third window indicator" (TWI) combines cVEMP
      thresholds with the ABG at 250 Hz to improve the ability to screen patients with
      SCD symptoms.

PMID- 29210948
TI  - Cochlear Implantation in a Patient With Sickle Cell Disease With Early Cochlear
      Sclerosis.
AB  - OBJECTIVE: We report a case of bilateral sudden sensorineural hearing loss (SNHL)
      and early cochlear sclerosis in a patient with sickle cell disease. METHODS: A 19
      year-old female presented with sequential bilateral sudden SNHL and early
      cochlear sclerosis. Cochlear implantation was performed. RESULTS: Early cochlear
      fibrosis in the hook region and basal turn was encountered within a few months of
      deafness. Implantation required serial dilation using various insertion guides.
      Postsurgical telemetry readings revealed 19 electrodes (7 paired basal
      electrodes, 5 single apical electrodes) in a good working order with low
      impedances in bilateral ears. Activation of the processors successfully provided
      access to the speech frequency range in both the ears. CONCLUSION: This is the
      first case of intraoperative documentation of rapid cochlear sclerosis in a
      patient with SNHL caused by sickle cell disease. Early cochlear implantation
      should be considered in these patients, and otolaryngologists should be aware of
      the possibility of rapid cochlear sclerosis without ossification in these
      patients.

PMID- 29210949
TI  - Clinical Characteristics and Treatment Outcomes for Patients With External
      Auditory Canal Cholesteatoma.
AB  - OBJECTIVE: We aimed to evaluate the clinical features and treatment outcomes for
      patients with idiopathic and secondary external auditory canal cholesteatoma
      (EACC), and to validate the treatment strategy from the perspective of hearing as
      well as etiology and staging. STUDY DESIGN: Retrospective case series. SETTING:
      Tertiary referral center and affiliated hospitals. PATIENTS: Fifty-eight patients
      with idiopathic EACC and 14 patients with secondary EACC. INTERVENTION:
      Conservative management and surgery. MAIN OUTCOME MEASURE: Air conduction (AC)
      pure-tone averages (PTAs) and mean air-bone gaps (ABGs). RESULTS: There were no
      significant differences between hearing values before and after conservative
      management for idiopathic EACC patients with stages I-III, indicating that
      hearing abilities were preserved. For idiopathic EACC patients with stage IV
      disease treated with surgery, the AC PTA threshold and mean ABG significantly
      improved from a preoperative value of 60.3 dB HL to a postoperative value of 32.4
      dB HL (p = 0.013), and from 34.3 to 9.5 dB HL (p < 0.001), respectively. For
      secondary EACC, the AC PTA threshold and mean ABG significantly improved from a
      preoperative value of 49.5 dB HL to a postoperative value of 23.2 dB HL (p <
      0.001), and from 31.4 to 6.7 dB HL (p < 0.001), respectively. CONCLUSION: The
      treatment modalities should be selected based on the perspective of hearing as
      well as the extent of disease and etiology. The early lesions can be treated
      conservatively, whereas the advanced lesions or cases refractory to conservative
      management require complete surgical removal of EACC.

PMID- 29210950
TI  - A Prospective Study of Pain From Magnetic Resonance Imaging With Cochlear Implant
      Magnets In Situ.
AB  - OBJECTIVE: To describe changes in pain associated with magnetic resonance imaging
      (MRI) with cochlear implant magnets in place. STUDY DESIGN: Prospective, single
      arm study. SETTING: Tertiary referral center. SUBJECTS: Adults with cochlear
      implants requiring MRI. INTERVENTION: Tight head wrapping over internal device
      during MRI. MAIN OUTCOME MEASURES: Change in pain score using an 11-point visual
      analogue scale, duration/completion of MRI, body mass index (BMI), quality of
      pain, status of the skin, functioning of implant, displacement/polarity change of
      magnet, willingness to repeat MRI without magnet removal. RESULTS: A total of 27
      subjects obtained 42 MRI scans. Subjects were 59% male with age range of 21 to 80
      years. All three manufacturers were represented. Forty-eight percent of scans
      imaged the brain/head while 52% imaged other sites. The mean individual change in
      pain was 3.9 (SD 3.5, range 0-10). The pain was most commonly described as
      "pressure", "heat", or "sharp". There was no significant correlation between
      change in pain and scan duration, BMI, or body part imaged. Eighty-eight percent
      of the scans were completed. There were no skin complications except temporary
      erythema (29%) and there were no magnet/device complications. Eighty-eight
      percent said they would undergo MRI without magnet removal again. CONCLUSION: The
      pain associated with obtaining an MRI without cochlear implant magnet removal is
      highly variable. Increase in pain is not related to duration of MRI scan, body
      part imaged, or BMI. Despite the pain, almost all patients prefer MRI scanning
      with the magnet in place, to avoid two surgical procedures.

PMID- 29210951
TI  - Health Burden and Socioeconomic Disparities From Hearing Loss: A Global
      Perspective.
AB  - OBJECTIVES/HYPOTHESIS: To characterize the disability-related health burden of
      hearing loss (HL) at a global level, with a focus on socioeconomic health
      disparities. METHODS: The global burden of HL, as calculated by disability
      adjusted life years (DALYs) per 100,000 individuals, was evaluated for 184
      countries. Data from 5-year intervals encompassing 1990 to 2015 were organized by
      human development index (HDI) categorizations as specified by the U.N.
      Development Program (UNDP). Gini coefficients and concentration indices were used
      to evaluate global inequality in HL burden over this time period. RESULTS: There
      was a global lack of improvement in hearing loss burden over 25 years. National
      HL burden, as measured by age-standardized DALYs, had an inverse relationship
      with successive level of development (p < 0.0001). Global inequalities in HL
      burden as measured by the concentration index decreased from 1990 to 2005,
      remained stable between 2005 and 2010, and slightly increased from 2010 to 2015.
      Central Sub-Saharan Africa, followed by Eastern Sub-Saharan Africa and South
      Asia, had the greatest rates of disease burden in 2015. CONCLUSIONS: To our
      knowledge, this analysis is the first to investigate socioeconomic-related
      inequalities in hearing loss burden using statistical tools such as the Gini
      coefficient and concentration index. Although inequalities have largely decreased
      in recent decades, the global burden of hearing loss remains high and there are
      recent signs of increased inequality. These data suggest that a greater
      distribution of hearing care resources may need to be directed towards developing
      countries to combat global hearing loss burden. LEVEL OF EVIDENCE: III.

PMID- 29210952
TI  - Survey of the American Neurotology Society on Cochlear Implantation: Part 1,
      Candidacy Assessment and Expanding Indications.
AB  - OBJECTIVE: To examine practice variance of cochlear implant candidacy assessment
      and off-label indications across centers in the United States. METHODS: Cross
      sectional survey of the American Neurotology Society (ANS). RESULTS: A total of
      81 surveys were returned from ANS members who report regular involvement in
      cochlear implant care. Overall there was a broad distribution in age and clinical
      experience, with most respondents reporting ACGME accreditation in neurotology
      and employment at an academic center. The annual volume of cochlear implant
      surgeries varied considerably across centers.Seventy-eight percent of respondents
      performed cochlear implantation for at least one of the following indications
      within the last 2 years: profound hearing loss in children less than 12 months of
      age (35, 43%), children with asymmetrical hearing loss where at least one ear was
      better than performance cutoff for age (25, 31%), adults with asymmetrical
      hearing where at least one ear was better than the performance cutoff for adult
      criteria (49, 61%), single-sided deafness (37, 46%), and ipsilateral vestibular
      schwannoma (28, 35%). Centers with a higher annual implant volume more frequently
      performed off-label implantation in all queried populations (all, p<=0.001), and
      performed surgery on infants with congenital deafness at a younger age (p =
      0.013), compared with centers with lower surgical volume.When surveyed regarding
      speech perception testing practices for adult candidacy assessment, 75 (100%)
      respondents who answered this question reported routine use of AzBio sentences,
      42 (56%) CNC word scores, and 26 (35%) HINT testing; only 7 (9%) reported using
      BKB-SIN testing and 6 (8%) reported using CUNY scores. Fifty-one (68%) reported
      routine use of speech-in-noise testing to determine adult cochlear implant
      candidacy, 21 (28%) reported selective use only when patient scores were
      borderline in quiet, and 3 (4%) reported that their center does not currently use
      testing in noise for candidacy determination. Nineteen (26%) solely used +10 dB
      signal-to-noise ratio (SNR), 12 (16%) solely used +5 dB SNR, and 41 (55%) used
      both +10 and +5 dB SNR. Overall, 19% (N = 14) only perform unilateral
      implantation in the Medicare population, while 81% (N = 58) consider bilateral
      implantation. CONCLUSION: Significant variation in cochlear implant candidacy
      assessment and off-label implantation exists across centers and providers in the
      United States resulting in healthcare inequities. The high percentage of surgeons
      performing implantations for off-label or nontraditional indications reflects the
      overly restrictive and dated status of current implant guidelines. With greater
      adoption of more difficult speech perception testing in noise, careful clinical
      judgment is needed to maintain a favorable risk-benefit balance for prospective
      implant candidates.

PMID- 29210953
TI  - Acute effect of citrulline malate supplementation on upper-body resistance
      exercise performance in recreationally resistance-trained men.
AB  - To investigate the effect of citrulline malate (CM) supplementation on upper-body
      resistance exercise performance, twelve recreationally resistance-trained men
      (21.4+/-1.6 y; 163.0+/-46.2 cm; 85.0+/-12.4 kg) underwent two testing sessions
      administered in a randomized, double-blind fashion. During each visit,
      participants were provided either 8 g of CM or a placebo (PL) 40 min prior to
      beginning a standardized warm-up and initiating a barbell bench press resistance
      exercise protocol consisting of 5 sets of 15 repetitions at 75% 1RM with 2-minute
      rest intervals. Participants were instructed to complete as many repetitions as
      possible until either reaching 15 repetitions or muscular failure. Total number
      of repetitions performed and power output were recorded for each set. Subjective
      measures of energy, focus, fatigue, and perceived exertion, along with muscle
      thickness of the triceps brachii, were assessed before and after exercise.
      Significant (p<0.05) main effects for time were observed for all variables except
      for subjective feelings of energy (p=0.085). A group * time interaction (F=2.86,
      p=0.034, n=0.21) was observed for repetitions performed, where participants
      performed more (p=0.015) repetitions on set 3 during PL (5.7+/-1.2 repetitions)
      compared to CM (4.6+/-1.2 repetitions). However, during set 4, participants
      tended (p=0.089) to perform more repetitions during CM (4.8+/-1.8 repetitions)
      compared to PL (4.3+/-1.3 repetitions). No other differences were observed
      between trials. Supplementation with 8 grams of CM 40 min prior to the barbell
      bench press resistance exercise protocol did not increase exercise performance,
      augment the muscle swelling response to training, or alter subjective measures of
      focus, energy, and fatigue in recreationally resistance-trained men.

PMID- 29210954
TI  - Examining the Influence of Exercise Intensity and Hydration on Gastrointestinal
      Temperature in Collegiate Football Players.
AB  - DeMartini-Nolan, JK, Martschinske, JL, Casa, DJ, Lopez, RM, Stearns, RL, Ganio,
      MS, and Coris, E. Examining the influence of exercise intensity and hydration on
      gastrointestinal temperature in collegiate football players. J Strength Cond Res
      32(10): 2888-2896, 2018-Debate exists regarding the influence of intensity and
      hydration on body temperature during American football. The purpose of this study
      was to observe body core temperature responses with changes in intensity and
      hydration. Twenty-nine male football players (age = 21 +/- 1 year, height = 187
      +/- 9 cm, mass = 110.1 +/- 23.5 kg, body mass index [BMI] = 31.3 +/- 5.0, and
      body surface area [BSA] = 2.34 +/- 0.27 m) participated in 8 days of practice in
      a warm environment (wet bulb globe temperature: 29.6 +/- 1.6 degrees  C).
      Participants were identified as starters (S; n = 12) or nonstarters (n = 17) and
      linemen (L; n = 14) or nonlinemen (NL; n = 15). Variables of interest included
      core body temperature (T), hydration status, and physical performance
      characteristics as measured by a global positioning system. Intensity measures of
      average heart rate (138 +/- 9 bpm), low-velocity movement (4.2 +/- 1.7%), high
      velocity movement (0.6 +/- 0.6%), and average velocity (0.36 +/- 0.10 m.s)
      accounted for 42% of the variability observed in T (38.32 +/- 0.34 degrees  C, r
      = 0.65, p = 0.01). Hydration measures (percent body mass loss = -1.56 +/- 0.80%,
      urine specific gravity [Usg] = 1.025 +/- 0.006, and urine color [Ucol] = 6 +/- 1)
      did not add to the prediction of T (p = 0.83). Metrics of exercise intensity
      accounted for 39% of the variability observed in maximum T (38.83 +/- 0.42
      degrees  C, r = 0.62, p = 0.02). Hydration measures did not add to this
      prediction (p = 0.40). Low-velocity movement, high-velocity movement, average
      velocity, BMI, and BSA were significantly different (p = 0.002, p < 0.001, p =
      0.02, p < 0.001, p < 0.001, respectively) between L vs. NL. Heart rate and T were
      not different between L and NL (p > 0.05). Exercise intensity primarily accounted
      for the rise in core body temperature. Although L spent less time at higher
      velocities, T was similar to NL, suggesting that differences in BMI and BSA added
      to thermoregulatory strain.

PMID- 29210955
TI  - Comparison Between Power Off-Ice Test and Performance on-Ice Anaerobic Testing.
AB  - The importance of specific testing has been shown in ice hockey performance and
      the understanding and connection between them may lead to adapting training and
      follow up in elite athletes. The aim of the present study was to compare two off
      ice power tests with performances on ice with a complete professional hockey
      team. The broad jump test and the vertical jump test were used for the off-ice
      evaluations, while the SAS-40 and the repeated skate sprint modify (RSSm) tests
      were used as the performance variables. 31 players (3 goalkeepers, 10 defence
      players and 18 forward players) from the National Hockey League (NHL) performed
      during a summer camp. Study includes four evaluation sessions with a 48-hour time
      interval in each test. All dependent variables were expressed by their means and
      standard deviations form (Mean SD). Correlation analyses were conducted for each
      group to establish the relation between off-ice tests and the on-ice performance
      test. The two jumps were correlated (r2= 0.45 p<0.01). There was a significant
      correlation between vertical jump and best trial during SAS-40 for the defence
      player but not for forward players (r2= 0.76 p=0.02; r2= 0.21 p= 0.16
      respectively). There was a significant correlation between broad jump and best
      trial during SAS-40 for forward players but not for defensive players (r2= 0.75
      p<0.01; r2= 0.19 p= 0.28 respectively).Results of this study seem to show that
      the positions have specific ability needs in assessment and that needs to be
      taken into consideration for the choice of tests, mostly during the off-ice
      tests.

PMID- 29210956
TI  - Motor Skills of Obese and Severely Obese Children and Adolescents - A CIRCUIT
      Study.
AB  - During childhood, excessive weight is negatively associated with the development
      of motor skills, with children with overweight or obesity having poorer motor
      skills compared to children with normal weight. The objectives of the current
      study are to identify the differences in motor skills between children and
      adolescent with obesity and severe obesity and the extent of this difference. To
      do so, we examined cross-sectionally 165 subjects. Physical fitness was analyzed
      in both participants with obesity (>97-99.9 BMI percentile) and severe obesity
      (>99.9 BMI percentile) using eight standardized tests: sit-and-reach, grip force,
      sit-ups, push-ups, balance, hand-eye coordination, standing long jump and 5-meter
      shuttle run. Poorer performance were observed in participants with severe obesity
      in sit-ups (children: 59%; 18.6+/-17.0 percentile value vs. 29.5+/-23.2
      percentile value, p=0.008), balance (adolescent: 59%; 12.1+/-12.2 sec. v. 19.3+/
      13.9 sec., p=0.034) and in the 5-meter shuttle run (children: 49%; 14.0+/-13.9
      percentile value vs. 20.8 +/- 19.4 percentile value, p=0.046; adolescents: 11%;
      13.2+/-2.2 sec. vs. 11.8+/-1.6 sec., p=0.008) compared to obese counterparts. In
      conclusion, while physical performance was found to be similar between the
      different obesity levels for the majority of tests, youth with severe obesity
      demonstrated impairments ranging from 11 to 59% in specific tests.

PMID- 29210957
TI  - The Physiological and Performance Effects of Caffeine Gum Consumed During A
      Simulated Half-Time By Professional Academy Rugby Union Players.
AB  - Despite the prevalence of caffeine as an ergogenic aid, few studies have examined
      the use of caffeinated gums, especially during half-time in team sports. The
      physiological (blood lactate, salivary hormone concentrations) and performance
      (repeated sprints, cognitive function) effects of consuming caffeine gum during a
      simulated half-time were examined. Professional academy rugby union players
      (n=14) completed this double-blind, randomized, counterbalanced study. Following
      pre-exercise measurements , players chewed a placebo (PL) gum for five min before
      a standardized warm-up and completing repeated sprint testing (RSSA1).
      Thereafter, during a 15 min simulated half-time period, players chewed either
      caffeine (CAF: 400 mg; 4.1 +/- 0.5 mg.kg) or PL gum for five min before
      completing a second repeated sprint test (RSSA2). Blood lactate, salivary
      testosterone and cortisol concentrations, and indices of cognitive function
      (i.e., reaction time and Stroop test) were measured at baseline, pre-RSSA1, post
      RSSA1, pre-RSSA2 and post-RSSA2. Sprint performance was not affected by CAF
      (P=0.995) despite slower sprint times following the first sprint of both RSSA
      tests (all P<0.002). Following half-time, salivary testosterone increased by 70%
      (+97+/-58 pg.mL) in CAF versus PLA (P<0.001) whereas salivary cortisol remained
      unchanged (P=0.307). Cognitive performance was unaffected by time and trial (all
      P>0.05). Although performance effects were absent, chewing caffeine gum increased
      the salivary testosterone concentrations of professional rugby union players over
      a simulated half-time. Practitioners may therefore choose to recommend caffeine
      gum between successive exercise bouts due to the increases in salivary
      testosterone observed; a variable associated with increased motivation and high
      intensity exercise performance.

PMID- 29210958
TI  - Reliability and Validity of a Submaximal Warm-up Test for Monitoring Training
      Status in Professional Soccer Players.
AB  - Rabbani, A, Kargarfard, M, and Twist, C. Reliability and validity of a submaximal
      warm-up test for monitoring training status in professional soccer players. J
      Strength Cond Res 32(2): 326-333, 2018-Two studies were conducted to assess the
      reliability and validity of a submaximal warm-up test (SWT) in professional
      soccer players. For the reliability study, 12 male players performed an SWT over
      3 trials, with 1 week between trials. For the validity study, 14 players of the
      same team performed an SWT and a 30-15 intermittent fitness test (30-15IFT) 7
      days apart. Week-to-week reliability in selected heart rate (HR) responses
      (exercise heart rate [HRex], heart rate recovery [HRR] expressed as the number of
      beats recovered within 1 minute [HRR60s], and HRR expressed as the mean HR during
      1 minute [HRpost1]) was determined using the intraclass correlation coefficient
      (ICC) and typical error of measurement expressed as coefficient of variation
      (CV). The relationships between HR measures derived from the SWT and the maximal
      speed reached at the 30-15IFT (VIFT) were used to assess validity. The range for
      ICC and CV values was 0.83-0.95 and 1.4-7.0% in all HR measures, respectively,
      with the HRex as the most reliable HR measure of the SWT. Inverse large (r = 
      0.50 and 90% confidence limits [CLs] [-0.78 to -0.06]) and very large (r = -0.76
      and CL, -0.90 to -0.45) relationships were observed between HRex and HRpost1 with
      VIFT in relative (expressed as the % of maximal HR) measures, respectively. The
      SWT is a reliable and valid submaximal test to monitor high-intensity
      intermittent running fitness in professional soccer players. In addition, the
      test's short duration (5 minutes) and simplicity mean that it can be used
      regularly to assess training status in high-level soccer players.

PMID- 29210959
TI  - ACUTE FROSTED RETINAL PERIPHLEBITIS IN A PATIENT WITH MEDITERRANEAN FEVER.
AB  - PURPOSE: To present a case of frosted branch periphlebitis in a young Armenian
      patient with familial Mediterranean fever. METHODS: Case report. RESULTS: A 37
      year-old man presented with a unilateral decreased visual acuity and floaters for
      4 days on the left eye (LE). Visual acuity was 20/20 in the right eye (RE) and
      20/28 in the LE. Anterior segment and fundus examinations of the RE were normal.
      Slit-lamp examination of LE revealed a mild nongranulomatous anterior uveitis and
      vitritis. Intraocular pressure was 19 mmHg in the RE and 12 mmHg in the LE.
      Fundoscopy of the LE showed typical appearance of frosted branch periphlebitis
      with perivascular sheathing of the retinal veins and scattered retinal
      hemorrhages. Fluorescein angiography of the RE was normal. The LE showed optic
      disk and segmented vascular staining without macular leakage. Optical coherence
      tomography of the RE was normal; LE demonstrated a localized macular thickening
      and few intraretinal cysts. The detailed ophthalmologic history was negative. The
      general history and workup were significant for familial Mediterranean fever and
      a positive lupus anticoagulant. One week later, the fundus findings worsened with
      a severe decrease of visual acuity of the LE to 20/200. A single intravitreal
      (IVT) injection of bevacizumab was performed. Three weeks after injection, fundus
      findings progressively improved with a decrease of the macular thickening and an
      improvement of the visual acuity to 20/25. Clinical improvement continued up to
      the last visit (19 weeks after the injection) with a visual acuity that reached
      back 20/20 with no signs of active inflammation. CONCLUSION: This case
      demonstrates a possible association between unilateral frosted branch
      periphlebitis and familial Mediterranean fever.

PMID- 29210960
TI  - DISLODGEMENT OF FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT INTO THE INFUSION
      CANNULA DURING VITRECTOMY FOR RETINAL DETACHMENT.
AB  - BACKGROUND/PURPOSE: To report a case of dislodgement of an Iluvien (fluocinolone
      acetonide) intravitreal implant into the infusion cannula during pars plana
      vitrectomy for retinal detachment. METHODS: The patient's surgery was video
      recorded, and the medical notes were reviewed retrospectively. RESULTS: A patient
      developed a macula off retinal detachment over 1 year after intravitreal
      injection of Iluvien for diabetic maculopathy. The patient underwent pars plana
      vitrectomy, removal of implant, and successful retinal reattachment. Although we
      planned to remove the implant through a sclerostomy, we were not able to localize
      it after performing peripheral indented vitrectomy. As the intraocular pressure
      was fluctuating, we suspected that the implant might have dislodged into the
      infusion cannula. However, despite increasing the intraocular pressure to 60 mmHg
      and performing repeated fluid-air exchange, we could not eject the implant back
      into the vitreous cavity. Therefore, after completing the surgery safely, we
      flushed the infusion cannula with balanced salt solution and we found the
      implant. CONCLUSION: Increasing the intraocular pressure and performing fluid-air
      exchange were not sufficient to eject the implant probably because of the strong
      surface adherence between the infusion cannula and the implant's coating
      material. We, therefore, recommend removing and flushing the infusion cannula if
      the implant cannot be localized in the eye. In addition, clinicians should be
      aware that a fluctuating intraocular pressure might be the first sign of a
      partially blocked infusion cannula by the implant.

PMID- 29210961
TI  - THERAPEUTIC VITRECTOMY AS AN ADJUNCT TREATMENT TO SYSTEMIC CHEMOTHERAPY FOR
      INTRAOCULAR LYMPHOMA.
AB  - PURPOSE: To report the outcome of a previously vitrectomized eye having less
      lymphoma disease burden compared with the contralateral nonvitrectomized eye over
      the course of 3.5 years while on systemic chemotherapy. METHODS: Case report.
      RESULTS: A 51-year-old man with vitreoretinal lymphoma with central nervous
      system involvement underwent vitrectomy in his left eye. Over the following 3.5
      years on systemic chemotherapy, the left eye had less lymphoma disease burden
      compared with the contralateral nonvitrectomized right eye. CONCLUSION:
      Therapeutic vitrectomy may be a useful adjunct to systemic chemotherapy in
      vitreoretinal lymphoma, particularly in cases of vitreous predominant disease
      manifestation.

PMID- 29210962
TI  - LONG-TERM MULTIMODAL IMAGING OF OCULAR FINDINGS ASSOCIATED WITH THIAMINE
      RESPONSIVE MEGALOBLASTIC ANEMIA.
AB  - PURPOSE: To report on 5-year multimodal imaging of ocular findings in a patient
      with thiamine-responsive megaloblastic anemia. METHODS: Observational case
      report. RESULTS: A 20-year-old-man with a history of thiamine-responsive
      megaloblastic anemia demonstrated a symmetric bull's eye maculopathy. Spectral
      domain optical coherence tomography revealed disruption of the parafoveal
      ellipsoid zone, fundus autofluorescence demonstrated foveal hypoautofluorescence,
      and full-field electroretinogram testing revealed a decreased photopic and
      scotopic response consistent with cone-rod dystrophy. His best-corrected visual
      acuity remained stable over 5 years at 20/50 in the right eye and 20/40 in the
      left eye, and visual field testing remained stable over time. CONCLUSION: Ocular
      manifestations in thiamine-responsive megaloblastic anemia are uncommon and
      variable. In this case, multimodal imaging and electroretinogram findings are
      consistent with cone-rod degeneration. The patient is taking daily thiamine
      supplementation, and visual acuity, funduscopic examination, spectral domain
      optical coherence tomography, and autofluorescence remained stable over a 5-year
      period.

PMID- 29210963
TI  - CENTRAL ELLIPSOID LOSS ASSOCIATED WITH CONE DYSTROPHY AND KCNV2 MUTATION.
AB  - PURPOSE: To report a case of central ellipsoid loss with supernormal rod
      electroretinogram and KCNV2 gene mutation. METHODS: Retrospective case report.
      PATIENT: Thirty-eight-year-old man. RESULTS: We report a patient with
      longstanding vision loss and photophobia who illustrated central atrophy of the
      inner segment ellipsoid zone band on spectral domain optical coherence
      tomography. Fundus autofluorescence displayed mild perifoveal mottled
      autofluorescence. Electroretinography demonstrated a diminished rod-isolated
      response with delayed timing but a normal dark-adapted maximal response to bright
      flashes. Cone-mediated responses under light-adapted conditions were abnormal
      with evidence of selective loss of the b wave and a normal a wave consistent with
      cone dystrophy with supernormal rod electroretinogram. Genetic testing
      demonstrated a frameshift mutation in the KCNV2 gene. CONCLUSION: Cone dystrophy
      with supernormal rod electroretinogram is believed to be a monogenic disease due
      to KCNV2 gene mutations that affect a transmembrane potassium channel found in
      rod and cone photoreceptors. We report the multimodal retinal findings associated
      with a signature electroretinogram in this disorder. Clinicians should consider
      this rare condition when evaluating patients with central ellipsoid loss and
      associated cone dystrophy.

PMID- 29210964
TI  - PERIVASCULAR GRANULOMATA IN THE RETINA DEMONSTRATED BY EN FACE OPTICAL COHERENCE
      TOMOGRAPHY IN A PATIENT WITH BLAU SYNDROME.
AB  - PURPOSE: To describe the multimodal retinal imaging findings of a case of Blau
      syndrome. METHODS: Case report. The multimodal retinal imaging findings,
      including widefield angiography, cross-sectional and en face spectral domain
      optical coherence tomography, and optical coherence tomography angiography, of a
      case of Blau syndrome are described. RESULTS: A 12-year-old Hispanic girl with
      polyarticular arthritis, skin rash, and panuveitis was diagnosed with a rare
      condition referred to as Blau syndrome. Genetic testing identified an NOD2
      mutation. Cross-sectional and en face optical coherence tomography illustrated
      presumed perivascular granulomata in the middle retina. Optical coherence
      tomography angiography failed to display flow within these lesions. CONCLUSION:
      This report illustrates the presence of a remarkable distribution of
      perivascular, presumably granulomatous, retinal lesions in the middle retina.
      Similar perivascular granulomata have been noted in the histopathological
      analysis of ocular sarcoidosis.

PMID- 29210965
TI  - A CASE OF RETINAL METASTASIS OF LARYNGEAL SQUAMOUS CELL CARCINOMA WITH
      HISTOPATHOLOGIC CONFIRMATION BY VITRECTOMY-ASSISTED EN BLOCK EXTRACTION.
AB  - BACKGROUND/PURPOSE: To present a case report of retinal metastasis of laryngeal
      squamous cell carcinoma that was diagnosed by a histopathologic finding from the
      surgically extracted tumor tissue. METHODS: A 66-year-old man, who was suffered
      from the treatment-resistant laryngeal carcinoma, was referred to our department
      because of visual field defect in his right eye. A fundus examination revealed a
      parafoveal white retinal lesion, which rapidly expanded to the central fovea and
      decreased the visual acuity. A tissue extraction by 27G pars plana vitrectomy was
      performed to confirm the diagnosis. RESULTS: The abnormal retinal tissue was
      extracted en block through 10-mm sclerocorneal tunnel during pars plana
      vitrectomy. The histopathologic findings revealed that the retinal lesion was
      retinal metastasis of laryngeal carcinoma. CONCLUSION: We must keep in mind that
      retinal metastasis can be one of the differential diagnoses for white retinal
      lesions of unknown cause.

PMID- 29210969
TI  - Postoperative Pain Among Patients After Day-Case Surgery.
AB  - Postoperative pain occurs at a high incidence after day-case surgery, with many
      patients reporting moderate to severe pain. A cross-sectional design was used in
      this study to estimate the prevalence of postoperative pain in the early
      postoperative period after day-case surgery and to determine whether there is a
      relationship between demographic and clinical variables. A convenient sample of
      300 patients, aged between 18 and 80 years, was selected from all postoperative
      patients after day-case surgery over a period of 6 months. At the first 2 hr
      after surgery, about 70% of patients had either no pain or mild pain at rest and
      about 30% of patients had moderate to severe pain. About one third of these
      patients (103; 35.8%) reported mild pain, and about 43% of patients had moderate
      to severe pain on movement in the first 2 hr after surgery. Furthermore, 25.3%
      and 41.3% of the patients reported moderate to severe pain during the first 24 hr
      after hospital discharge at rest and on movement, respectively. Female patients
      had significantly higher pain scores than male patients (p < .001). Significant
      decrease in pain scores was reported in the first 2 hr after surgery (mean = 2.2,
      SD = 2) and within the first 24 hr after discharge (mean = 1.8, SD = 2.2, t(288)
      = 4.3, p =. 005) at rest. The prevalence of pain among postoperative patients
      after day-care surgery in Jordan is high. Young adult and female patients have
      higher pain scores after day-case surgery.

PMID- 29210970
TI  - Evaluating the Implementation of a Preemptive, Multimodal Analgesia Protocol in a
      Plastic Surgery Office.
AB  - Many patients undergoing plastic surgery experience significant pain
      postoperatively. The use of preemptive, multimodal analgesia techniques to reduce
      postoperative pain has been widely described in the literature. This quality
      improvement project evaluated the implementation of a preemptive, multimodal
      analgesia protocol in an office-based plastic surgery facility to decrease
      postoperative pain, decrease postoperative opioid consumption, decrease
      postanesthesia care time, and increase patient satisfaction. The project included
      adult patients undergoing surgical procedures at an outpatient plastic and
      cosmetic surgery office, and the protocol consisted of oral acetaminophen 1,000
      mg and gabapentin 1,200 mg. Using a pre-/postintervention design, data were
      collected from patient medical records and telephone interviews of patients
      receiving the standard preoperative analgesia regimen (preintervention group: n =
      24) and the evidence-based preemptive, multimodal analgesia protocol
      (postintervention group: n = 23). Results indicated no significant differences
      between the pre- and postintervention groups for any of the outcomes measured.
      However, results showed that patients in both groups experienced moderate to
      severe pain postoperatively. In addition, adverse side effects such as dizziness
      and drowsiness were higher in the postintervention group than in the
      preintervention group. Although this quality improvement project did not meet the
      goals it set out to achieve for patients undergoing plastic surgery, it did
      illustrate the substantial presence of pain after surgical procedures. Thus,
      clinicians need to continue to focus on identifying targeted treatment plans that
      use multimodal, non-opioid-based strategies to manage and prevent postoperative
      pain.

PMID- 29210971
TI  - Understanding Age, Memories, and How They Impact Aesthetic Practice.
AB  - According to the American Society for Aesthetic Plastic Surgery (), the number of
      nonsurgical treatments grew 650% from 1996 to 2016. As these procedures have
      evolved and improved, so have their ability to deliver results that enhance one's
      natural beauty and reverse the signs of aging. Many patients seek these
      procedures in the hopes of looking younger and more refreshed, but "younger" can
      be subjective and the patient's desired outcome may be difficult for
      practitioners to interpret. A recent study () of 350 women found that patients
      are carrying around a "memory photo" of themselves that is about 10 years younger
      than their actual age. Findings from this survey yielded new insights into
      patient perceptions of age and provides practitioners with a powerful new tool
      that can be applied in daily clinical practice.

PMID- 29210972
TI  - Met and Unmet Expectations for Breast Reconstruction in Early Posttreatment
      Breast Cancer Survivors.
AB  - The purpose of this study was to evaluate the prevalence of met and unmet
      expectations after breast reconstruction among breast cancer survivors following
      mastectomy. A secondary objective was to examine reasons women report their
      experiences of reconstructive surgery were better or worse than expected. As part
      of a larger study of breast cancer survivors, participants completed self
      administered questionnaires within 8 months of diagnosis and at 6, 12, and 18
      months later. At the 18-month follow-up, women who had breast reconstruction were
      asked whether their reconstruction was better, the same, or worse than expected.
      The sample consisted of 130 survivors (mean age = 48.5 years) who had breast
      reconstruction following mastectomy and completed the 18-month follow-up, 42% of
      whom reported their reconstruction was worse than expected and only 25% reported
      it was better. Most frequently reported reasons for reconstruction being worse
      than expected were related to appearance of the reconstructed breast and pain. A
      high percentage of patients with breast cancer undergoing breast reconstruction
      following mastectomy reported the results as worse than expected, with the
      primary reasons for dissatisfaction related to the feel and appearance of the
      reconstructed breast. Patients with breast cancer considering breast
      reconstruction need better preoperative education or understanding about what to
      expect from reconstruction.

PMID- 29210973
TI  - Manuka Honey: A Case Study of Severe Atopic Eczematous Dermatitis Reaction to
      Henna Tattoo.
AB  - Many mainstream medications were derived from plants and originally utilized in
      patient management well prior to the extensive research and testing processes of
      current pharmaceutical standards. The evolution of therapeutic management within
      the pharmaceutical and skin care industry often uses synthetic processing of
      products with less of a focus on the natural ingredients from which they were
      originally derived. However, more recently there has been a shift in
      pharmacological management to include the therapeutic use of more holistic
      medicines and practices and thus a broadening of the uses of nontraditional
      medical treatment options. This has been seen in the use of treatments, such as
      Manuka honey, for skin conditions and dermal injuries. It is often with off-label
      uses, or conditions resistant to other treatments, that then prompt the use of
      holistic products and the true value of the product is validated. As with the
      following case study, the example of the use of Manuka honey on a severe atopic
      contact dermatitis eczematous reaction provides further documentation and
      supportive evidence of the potential efficacy of the properties of this
      particular natural product.

PMID- 29210975
TI  - Multicenter Evaluation of a New Electrochemiluminescence Immunoassay for
      Everolimus Concentrations in Whole Blood.
AB  - BACKGROUND: The precise monitoring of everolimus, an immunosuppressant drug, is
      vital for transplant recipients due to its narrow therapeutic range. This study
      evaluated the analytical performance of a new electrochemiluminescence
      immunoassay (ECLIA) for everolimus concentrations in whole blood. METHODS:
      Accuracy, imprecision, and sensitivity studies for the Roche Elecsys everolimus
      ECLIA were performed at 5 European laboratories. The ECLIA was compared with
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, as well as the
      Quantitative Microsphere System everolimus assay. RESULTS: Everolimus ECLIA
      accuracies were within the range 100% +/- 9%. Coefficients of variation (CVs)
      across the target range were <=4.8% for repeatability and <=8.4% for intermediate
      imprecision, whereas multisite reproducibility at lower (2.71 mcg/L) and higher
      everolimus concentrations (3.0-30.0 mcg/L) resulted in CVs of <=13.7% and
      <=12.4%, respectively. The CV at the assay's lower limit of quantification
      without considering bias was excellent, estimated as <=9.3% at 0.5 mcg/L. The
      weighted Deming regression analysis, used for comparison of the results obtained
      by everolimus ECLIA and by LC-MS/MS methods, yielded a slope of 1.21 [95%
      confidence interval (CI): 1.15-1.26], intercept of 0.478 mcg/L (95% CI: 0.241
      0.716), and a Pearson correlation coefficient (r) of 0.91. A single-site
      comparison between the ECLIA and the Quantitative Microsphere System assay
      revealed a slope of 1.05 (95% CI: 0.917-1.17), intercept of 1.03 mcg/L (95% CI:
      0.351-1.70), and r of 0.91. CONCLUSIONS: Based on these results, the Roche
      Elecsys everolimus ECLIA can be considered suitable for routine therapeutic drug
      monitoring. A positive bias was observed with respect to LC-MS/MS methods,
      suggesting that it may be necessary to rebaseline individual patients when
      switching from LC-MS/MS to the ECLIA; however, this must also be considered for
      any change of method for everolimus measurement.

PMID- 29210976
TI  - Therapeutic Drug Monitoring of Asparaginase Activity-Method Comparison of MAAT
      and AHA Test Used in the International AIEOP-BFM ALL 2009 Trial.
AB  - BACKGROUND: In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE)
      activity was monitored after each dose of pegylated Escherichia coli ASE (PEG
      ASE). Two methods were used: the aspartic acid beta-hydroxamate (AHA) test and
      medac asparaginase activity test (MAAT). As the latter method overestimates PEG
      ASE activity because it calibrates using E. coli ASE, method comparison was
      performed using samples from the AIEOP-BFM ALL 2009 trial. METHODS: PEG-ASE
      activities were determined using MAAT and AHA test in 2 sets of samples (first
      set: 630 samples and second set: 91 samples). Bland-Altman analysis was performed
      on ratios between MAAT and AHA tests. The mean difference between both methods,
      limits of agreement, and 95% confidence intervals were calculated and compared
      for all samples and samples grouped according to the calibration ranges of the
      MAAT and the AHA test. RESULTS: PEG-ASE activity determined using the MAAT was
      significantly higher than when determined using the AHA test (P < 0.001; Wilcoxon
      signed-rank test). Within the calibration range of the MAAT (30-600 U/L), PEG-ASE
      activities determined using the MAAT were on average 23% higher than PEG-ASE
      activities determined using the AHA test. This complies with the mean difference
      reported in the MAAT manual. With PEG-ASE activities >600 U/L, the discrepancies
      between MAAT and AHA test increased. Above the calibration range of the MAAT
      (>600 U/L) and the AHA test (>1000 U/L), a mean difference of 42% was determined.
      Because more than 70% of samples had PEG-ASE activities >600 U/L and required
      additional sample dilution, an overall mean difference of 37% was calculated for
      all samples (37% for the first and 34% for the second set). CONCLUSIONS:
      Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean
      difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and
      600 U/L. The discrepancy increased in samples with >600 U/L PEG-ASE activity,
      which will be especially relevant when evaluating high PEG-ASE activities in
      relation to toxicity, efficacy, and population pharmacokinetics.

PMID- 29210977
TI  - Influence of Comedication on Levetiracetam Pharmacokinetics.
AB  - BACKGROUND: To evaluate the effect of concomitant antiepileptic therapy on
      levetiracetam (LEV) pharmacokinetics. METHODS: A 6-year retrospective
      observational study. Patients were grouped according to the antiepileptic drug
      used as concomitant medication: group A, LEV in monotherapy; group B, LEV +
      enzyme-inducing antiepileptic drugs (EIAEDs); and group C, LEV + non-enzyme
      inducing antiepileptic drugs (NEIAEDs). Apparent oral levetiracetam clearance
      (LEV CL/F) and basal serum levetiracetam concentrations (LEV C0) were compared
      among the different groups by analysis of variance. RESULTS: A total of 330 LEV
      C0 corresponding to 205 patients (56% men) were identified. The mean (+/-SD) of
      LEV CL/F in group A (n = 180), B (n = 92), and C (n = 58) was 4.41 +/- 2.06 L/h,
      7.23 +/- 3.72 L/h, and 4.87 +/- 1.65 L/h, respectively. EIAEDs increased LEV CL/F
      (L/h) by 64% compared with the monotherapy group and by 48% compared with the
      NEIAEDs group. The greatest induction in LEV CL/F, compared with the LEV
      monotherapy group, was observed with carbamazepine, followed by oxcarbazepine and
      phenobarbital, and was increased by 81%, 64%, and 44%, respectively. LEV C0
      values were significantly lower in the EIAEDs group than in the monotherapy group
      (17.30 +/- 7.77 versus 20.08 +/- 9.69 mcg/mL; P = 0.038) or indeed the NEIAEDs
      group (17.30 +/- 7.77 versus 20.49 +/- 9.46 mcg/mL; P = 0.027). CONCLUSIONS:
      Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas
      carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher
      than that of the monotherapy group. These data suggest that monitoring LEV serum
      concentration during polytherapy with EIAEDs is indicated.

PMID- 29210978
TI  - Heterogeneous Data Fusion Method to Estimate Travel Time Distributions in
      Congested Road Networks.
AB  - Travel times in congested urban road networks are highly stochastic. Provision of
      travel time distribution information, including both mean and variance, can be
      very useful for travelers to make reliable path choice decisions to ensure higher
      probability of on-time arrival. To this end, a heterogeneous data fusion method
      is proposed to estimate travel time distributions by fusing heterogeneous data
      from point and interval detectors. In the proposed method, link travel time
      distributions are first estimated from point detector observations. The travel
      time distributions of links without point detectors are imputed based on their
      spatial correlations with links that have point detectors. The estimated link
      travel time distributions are then fused with path travel time distributions
      obtained from the interval detectors using Dempster-Shafer evidence theory. Based
      on fused path travel time distribution, an optimization technique is further
      introduced to update link travel time distributions and their spatial
      correlations. A case study was performed using real-world data from Hong Kong and
      showed that the proposed method obtained accurate and robust estimations of link
      and path travel time distributions in congested road networks.

PMID- 29210979
TI  - Morphological Variation and Inter-Relationships of Quantitative Traits in Enset
      (Ensete ventricosum (welw.) Cheesman) Germplasm from South and South-Western
      Ethiopia.
AB  - Enset (Ensete ventricosum (Welw.) Cheesman) is Ethiopia's most important root
      crop. A total of 387 accessions collected from nine different regions of Ethiopia
      were evaluated for 15 quantitative traits at Areka Agricultural Research Centre
      to determine the extent and pattern of distribution of morphological variation.
      The variations among the accessions and regions were significant (p <= 0.01) for
      all the 15 traits studied. Mean for plant height, central shoot weight before
      grating, and fermented squeezed kocho yield per hectare per year showed regional
      variation along an altitude gradient and across cultural differences related to
      the origin of the collection. Furthermore, there were significant correlations
      among most of the characters. This included the correlation among agronomic
      characteristics of primary interest in enset breeding such as plant height,
      pseudostem height, and fermented squeezed kocho yield per hectare per year.
      Altitude of the collection sites also significantly impacted the various
      characteristics studied. These results reveal the existence of significant
      phenotypic variations among the 387 accessions as a whole. Regional
      differentiations were also evident among the accessions. The implication of the
      current results for plant breeding, germplasm collection, and in situ and ex situ
      genetic resource conservation are discussed.

PMID- 29210980
TI  - Superconducting Quantum Interferometers for Nondestructive Evaluation.
AB  - We review stationary and mobile systems that are used for the nondestructive
      evaluation of room temperature objects and are based on superconducting quantum
      interference devices (SQUIDs). The systems are optimized for samples whose
      dimensions are between 10 micrometers and several meters. Stray magnetic fields
      from small samples (10 um-10 cm) are studied using a SQUID microscope equipped
      with a magnetic flux antenna, which is fed through the walls of liquid nitrogen
      cryostat and a hole in the SQUID's pick-up loop and returned sidewards from the
      SQUID back to the sample. The SQUID microscope does not disturb the magnetization
      of the sample during image recording due to the decoupling of the magnetic flux
      antenna from the modulation and feedback coil. For larger samples, we use a hand
      held mobile liquid nitrogen minicryostat with a first order planar gradiometric
      SQUID sensor. Low-Tc DC SQUID systems that are designed for NDE measurements of
      bio-objects are able to operate with sufficient resolution in a magnetically
      unshielded environment. High-Tc DC SQUID magnetometers that are operated in a
      magnetic shield demonstrate a magnetic field resolution of ~4 fT/?Hz at 77 K.
      This sensitivity is improved to ~2 fT/?Hz at 77 K by using a soft magnetic flux
      antenna.

PMID- 29210982
TI  - Invisible Security Printing on Photoresist Polymer Readable by Terahertz
      Spectroscopy.
AB  - We experimentally modulate the refractive index and the absorption coefficient of
      an SU-8 dry film in the terahertz region by UV light (362 nm) exposure with time
      dependency. Consequently, the refractive index of SU-8 film is increased by
      approximately 6% after UV light exposure. Moreover, the absorption coefficient
      also changes significantly. Using the reflective terahertz imaging technique, in
      addition, we can read security information printed by UV treatment on an SU-8
      film that is transparent in the visible spectrum. From these results, we
      successfully demonstrate security printing and reading by using photoresist
      materials and the terahertz technique. This investigation would provide a new
      insight into anti-counterfeiting applications in fields that need security.

PMID- 29210981
TI  - Health Co-Benefits of Green Building Design Strategies and Community Resilience
      to Urban Flooding: A Systematic Review of the Evidence.
AB  - Climate change is increasingly exacerbating existing population health hazards,
      as well as resulting in new negative health effects. Flooding is one particularly
      deadly example of its amplifying and expanding effect on public health. This
      systematic review considered evidence linking green building strategies in the
      Leadership in Energy and Environmental Design(r) (LEED) Rating System with the
      potential to reduce negative health outcomes following exposure to urban flooding
      events. Queries evaluated links between LEED credit requirements and risk of
      exposure to urban flooding, environmental determinants of health, co-benefits to
      public health outcomes, and co-benefits to built environment outcomes. Public
      health co-benefits to leveraging green building design to enhance flooding
      resilience included: improving the interface between humans and wildlife and
      reducing the risk of waterborne disease, flood-related morbidity and mortality,
      and psychological harm. We conclude that collaborations among the public health,
      climate change, civil society, and green building sectors to enhance community
      resilience to urban flooding could benefit population health.

PMID- 29210983
TI  - The Potential Pathogenic Contributions of Endothelial Barrier and Arterial
      Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins.
AB  - Shock with B. anthracis infection is particularly resistant to conventional
      cardiovascular support and its mortality rate appears higher than with more
      common bacterial pathogens. As opposed to many bacteria that lack exotoxins
      directly depressing hemodynamic function, lethal and edema toxin (LT and ET
      respectively) both cause shock and likely contribute to the high lethality rate
      with B. anthracis. Selective inhibition of the toxins is protective in infection
      models, and administration of either toxin alone in animals produces hypotension
      with accompanying organ injury and lethality. Shock during infection is typically
      due to one of two mechanisms: (i) intravascular volume depletion related to
      disruption of endothelial barrier function; and (ii) extravasation of fluid
      and/or maladaptive dilation of peripheral resistance arteries. Although some data
      suggests that LT can produce myocardial dysfunction, growing evidence
      demonstrates that it may also interfere with endothelial integrity thereby
      contributing to the extravasation of fluid that helps characterize severe B.
      anthracis infection. Edema toxin, on the other hand, while known to produce
      localized tissue edema when injected subcutaneously, has potent vascular relaxant
      effects that could lead to pathologic arterial dilation. This review will examine
      recent data supporting a role for these two pathophysiologic mechanisms
      underlying the shock LT and ET produce. Further research and a better
      understanding of these mechanisms may lead to improved management of B. anthracis
      in patients.

PMID- 29210985
TI  - Fatigue Damage Evaluation of Short Carbon Fiber Reinforced Plastics Based on
      Phase Information of Thermoelastic Temperature Change.
AB  - Carbon fiber-reinforced plastic (CFRP) is widely used for structural members of
      transportation vehicles such as automobile, aircraft, or spacecraft, utilizing
      its excellent specific strength and specific rigidity in contrast with the metal.
      Short carbon fiber composite materials are receiving a lot of attentions because
      of their excellent moldability and productivity, however they show complicated
      behaviors in fatigue fracture due to the random fibers orientation. In this
      study, thermoelastic stress analysis (TSA) using an infrared thermography was
      applied to evaluate fatigue damage in short carbon fiber composites. The
      distribution of the thermoelastic temperature change was measured during the
      fatigue test, as well as the phase difference between the thermoelastic
      temperature change and applied loading signal. Evolution of fatigue damage was
      detected from the distribution of thermoelastic temperature change according to
      the thermoelastic damage analysis (TDA) procedure. It was also found that fatigue
      damage evolution was more clearly detected than before by the newly developed
      thermoelastic phase damage analysis (TPDA) in which damaged area was emphasized
      in the differential phase delay images utilizing the property that carbon fiber
      shows opposite phase thermoelastic temperature change.

PMID- 29210984
TI  - Insight into the Mode of Action of Celangulin V on the Transmembrane Potential of
      Midgut Cells in Lepidopteran Larvae.
AB  - Celangulin V (CV) is the main insecticidal constituent of Celastrus angulatus.
      The V-ATPase H subunit of the midgut cells of lepidopteran larvae is the putative
      target protein of CV. Here, we compared the effects of CV on the midgut membrane
      potentials of Mythimna separata and Agrotis ipsilon larvae with those of the
      Cry1Ab toxin from Bacillus thuringiensis and with those of inactive CV-MIA, a
      synthetic derivative of CV. We investigated the changes in the apical membrane
      potentials (Vam) and basolateral membrane potentials (Vbm) of the midguts of
      sixth-instar larvae force-fed with the test toxins. We also measured the Vam and
      Vbm of larval midguts that were directly incubated with the test toxins. Similar
      to the effect of Cry1Ab, the Vam of CV-treated midguts rapidly decayed over time
      in a dose-dependent manner. By contrast, CV-MIA did not influence Vam. Meanwhile,
      the Vam of A. ipsilon larval midguts directly incubated with CV decayed less than
      that of M. separata larval midguts, whereas that of larvae force-fed with CV did
      not significantly change. Similar to Cry1Ab, CV did not affect the Vbm of
      isolated midguts. CV significantly inhibited V-ATPase activity in a dose
      dependent manner. Therefore, CV initially inhibits V-ATPase in the apical
      membrane and affects intracellular pH, homeostasis, and nutrient transport
      mechanisms in lepidopteran midgut cells.

PMID- 29210987
TI  - Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit
      Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide
      Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial
      Burden in Mice.
AB  - Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and
      the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in
      adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb
      antigens and appropriate immune stimulating adjuvants are needed to induce
      protective immunity targeted to the lungs, the primary sites of infections and
      pathology. We present here evidence in support of mucosal vaccination by the
      sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6
      adjuvanted with the glycolipid alpha-galactosylceramide (alpha-GalCer), a potent
      natural killer T (NKT) cell agonist. Vaccinated animals exhibited strong antigen
      specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and
      lungs. In general, inclusion of the alpha-GalCer adjuvant significantly enhanced
      these responses that persisted over 50 days. Furthermore, aerosolized Mtb
      infection of vaccinated mice resulted in a significant reduction of bacterial
      load of the lungs and spleens as compared to levels seen in naive controls or
      those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection
      induced by the Mtb antigens and-GalCer vaccine through sublingual route
      correlated with a TH1-type immunity mediated by antigen-specific IFN-gamma and IL
      2 producing T cells.

PMID- 29210986
TI  - Ubiquitin Specific Peptidase 22 Regulates Histone H2B Mono-Ubiquitination and
      Exhibits Both Oncogenic and Tumor Suppressor Roles in Cancer.
AB  - Ubiquitin-Specific Peptidase 22 (USP22) is a ubiquitin hydrolase, notably
      catalyzing the removal of the mono-ubiquitin moiety from histone H2B (H2Bub1).
      Frequent overexpression of USP22 has been observed in various cancer types and is
      associated with poor patient prognosis. Multiple mechanisms have been identified
      to explain how USP22 overexpression contributes to cancer progression, and thus,
      USP22 has been proposed as a novel drug target in cancer. However, gene re
      sequencing data from numerous cancer types show that USP22 expression is
      frequently diminished, suggesting it may also harbor tumor suppressor-like
      properties. This review will examine the current state of knowledge on USP22
      expression in cancers, describe its impact on H2Bub1 abundance and present the
      mechanisms through which altered USP22 expression may contribute to oncogenesis,
      including an emerging role for USP22 in the maintenance of genome stability in
      cancer. Clarifying the impact aberrant USP22 expression and abnormal H2Bub1
      levels have in oncogenesis is critical before precision medicine therapies can be
      developed that either directly target USP22 overexpression or exploit the loss of
      USP22 expression in cancer cells.

PMID- 29210988
TI  - Novel Mesoporous Flowerlike Iron Sulfide Hierarchitectures: Facile Synthesis and
      Fast Lithium Storage Capability.
AB  - The 3D flowerlike iron sulfide (F-FeS) is successfully synthesized via a facile
      one-step sulfurization process, and the electrochemical properties as anode
      materials for lithium ion batteries (LIBs) are investigated. Compared with bulk
      iron sulfide, we find that the unique structural features, overall flowerlike
      structure, composed of several dozen nanopetals and numerous small size iron
      sulfide particles embedded within the fine nanopetals, and hierarchical pore
      structure features provide signification improvements in lithium storage
      performance, with a high-rate discharge capacity of 779.0 mAh g-1 at a rate of 5
      A g-1, due to effectively alleviating the volume expansion during the
      lithiation/delithiation process, and shorting the diffusion length of both
      lithium ion and electron. Especially, an excellent cycling stability are
      achieved, a high discharge capacity of 890 mAh g-1 retained at a rate of 1.0 A g
      1, suggesting its promising applications in lithium ion batteries (LIBs).

PMID- 29210990
TI  - Grain Refinement Kinetics in a Low Alloyed Cu-Cr-Zr Alloy Subjected to Large
      Strain Deformation.
AB  - This paper investigates the microstructural evolution and grain refinement
      kinetics of a solution-treated Cu-0.1Cr-0.06Zr alloy during equal channel angular
      pressing (ECAP) at a temperature of 673 K via route BC. The microstructural
      change during plastic deformation was accompanied by the formation of the
      microband and an increase in the misorientations of strain-induced subboundaries.
      We argue that continuous dynamic recrystallization refined the initially coarse
      grains, and discuss the dynamic recrystallization kinetics in terms of
      grain/subgrain boundary triple junction evolution. A modified Johnson-Mehl-Avrami
      Kolmogorov relationship with a strain exponent of about 1.49 is used to express
      the strain dependence of the triple junctions of high-angle boundaries. Severe
      plastic deformation by ECAP led to substantial strengthening of the Cu-0.1Cr
      0.06Zr alloy. The yield strength increased from 60 MPa in the initial state to
      445 MPa after a total strain level of 12.

PMID- 29210991
TI  - Self-Supported Ni(P, O)x.MoOx Nanowire Array on Nickel Foam as an Efficient and
      Durable Electrocatalyst for Alkaline Hydrogen Evolution.
AB  - Earth-abundant and low-cost catalysts with excellent electrocatalytic hydrogen
      evolution reaction (HER) activity in alkaline solution play an important role in
      the sustainable production of hydrogen energy. In this work, a catalyst of Ni(P,
      O)x.MoOx nanowire array on nickel foam has been prepared via a facile route for
      efficient alkaline HER. Benefiting from the collaborative advantages of Ni(P, O)x
      and amorphous MoOx, as well as three-dimensional porous conductive nickel
      scaffold, the hybrid electrocatalyst shows high catalytic activity in 1 M KOH
      aqueous solution, including a small overpotential of 59 mV at 10 mA cm-2, a low
      Tafel slope of 54 mV dec-1, and excellent cycling stability.

PMID- 29210989
TI  - Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer:
      Models, Mechanisms and Questions.
AB  - Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa),
      suppression of systemic testosterone (T) has remained the most effective initial
      therapy for advanced disease although progression inevitably occurs. From the
      inception of clinical efforts to suppress androgen receptor (AR) signaling by
      reducing AR ligands, it was also recognized that administration of T in men with
      castration-resistant prostate cancer (CRPC) could result in substantial clinical
      responses. Data from preclinical models have reproducibly shown biphasic
      responses to T administration, with proliferation at low androgen concentrations
      and growth inhibition at supraphysiological T concentrations. Many questions
      regarding the biphasic response of PCa to androgen treatment remain, primarily
      regarding the mechanisms driving these responses and how best to exploit the
      biphasic phenomenon clinically. Here we review the preclinical and clinical data
      on high dose androgen growth repression and discuss cellular pathways and
      mechanisms likely to be involved in mediating this response. Although meaningful
      clinical responses have now been observed in men with PCa treated with high dose
      T, not all men respond, leading to questions regarding which tumor
      characteristics promote response or resistance, and highlighting the need for
      studies designed to determine the molecular mechanism(s) driving these responses
      and identify predictive biomarkers.

PMID- 29210992
TI  - Characterization of the Asiatic Acid Glucosyltransferase, UGT73AH1, Involved in
      Asiaticoside Biosynthesis in Centella asiatica (L.) Urban.
AB  - Centella asiatica (L.) Urban contains two ursane-type triterpene saponins,
      asiaticoside and madecassoside, as major secondary metabolites. In order to
      select candidate genes encoding UDP-glucosyltransferases (UGTs) involved in
      asiaticoside biosynthesis, we performed transcriptomic analysis of leaves
      elicited by methyl jasmonate (MeJA). Among the unigenes, 120 isotigs and 13
      singletons of unique sequences were annotated as UGTs, including 37 putative full
      length cDNAs, and 15 of the putative UGT genes were named according to the UGT
      committee nomenclature protocols. One of them, UGT73AH1, was characterized by
      heterologous expression in Escherichia coli BL21 (DE3) cells. After induction
      with IPTG, a total protein extract was assayed with UDP-glucose and asiatic acid.
      UPLC-QTOF/MS analysis showed that UGT73AH1 catalyzes the glycosylation of asiatic
      acid to its monoglucoside. It remains unclear whether glycosylation occurs on the
      triterpene C-2alpha, C-3beta, C-23, or C-28 position. However, it is very likely
      that UGT73AH1 glucosylates the C-28 position, because only C-28 bears a glucose
      moiety in the final pathway product of asiatic acid, while C-2alpha, C-3beta, and
      C-23 remain un-conjugated.

PMID- 29210993
TI  - Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic
      Biomarker of Urothelial Carcinomas.
AB  - The aim of this study to determine whether the aberrant N-glycosylated serum
      immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial
      carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from
      237 UC and also 96 prostate cancer as other cancer controls from our serum bank
      and also obtained-from 339 healthy volunteers (HV)-controls obtained from
      community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32
      types of N-glycan levels on Igs were determined by high-throughput N-glycomics
      and analyzed by multivariable discriminant analysis. We found five UC-associated
      aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc
      type N-glycan on Igs were significantly accumulated in UC patients. The
      diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans
      on Igs discriminated UC patients from HV and prostate cancer (PC) patients with
      92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of
      the dNGScore was 0.969 for UC detection that was much superior to that of urine
      cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can
      detect hematuria and urine cytology negative patients. The dNGscore based on
      aberrant N-glycosylation signatures of Igs were found to be promising diagnostic
      biomarkers of UCs.

PMID- 29210994
TI  - Iron Supplementation during Pregnancy and Infancy: Uncertainties and Implications
      for Research and Policy.
AB  - Iron is particularly important in pregnancy and infancy to meet the high demands
      for hematopoiesis, growth and development. Much attention has been given to
      conditions of iron deficiency (ID) and iron deficient anemia (IDA) because of the
      high global prevalence estimated in these vulnerable life stages. Emerging and
      preliminary evidence demonstrates, however, a U-shaped risk at both low and high
      iron status for birth and infant adverse health outcomes including growth,
      preterm birth, gestational diabetes, gastrointestinal health, and
      neurodegenerative diseases during aging. Such evidence raises questions about the
      effects of high iron intakes through supplementation or food fortification during
      pregnancy and infancy in iron-replete individuals. This review examines the
      emerging as well as the current understanding of iron needs and homeostasis
      during pregnancy and infancy, uncertainties in ascertaining iron status in these
      populations, and issues surrounding U-shaped risk curves in iron-replete pregnant
      women and infants. Implications for research and policy are discussed relative to
      screening and supplementation in these vulnerable populations, especially in
      developed countries in which the majority of these populations are likely iron
      replete.

PMID- 29210995
TI  - Support for Natural Small-Molecule Phenols as Anxiolytics.
AB  - Natural small-molecule phenols (NSMPs) share some bioactivities. The anxiolytic
      activity of NSMPs is attracting attention in the scientific community. This paper
      provides data supporting the hypothesis that NSMPs are generally anxiolytic. The
      anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol,
      protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were
      assayed with the elevated plus maze (EPM) test in mice. The oral doses were 5, 10
      and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10
      mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl
      group in 4-hydroxycinnamic acid (4-OH CA) was essential for the anxiolytic
      activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl
      CA). The in vivo spike recording of rats' hippocampal neurons also showed
      significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal
      spike recording results converged to indicate the hippocampal CA1 region might be
      a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides
      further experimental data supporting NSMPs sharing anxiolytic activity, which may
      have general implications for phytotherapy because small phenols occur
      extensively in herbal medicines.

PMID- 29210996
TI  - Theoretical Kinetic and Mechanistic Studies on the Reactions of CF3CBrCH2 (2-BTP)
      with OH and H Radicals.
AB  - CF3CBrCH2 (2-bromo-3,3,3-trifluoropropene, 2-BTP) is a potential replacement for
      CF3Br; however, it shows conflicted inhibition and enhancement behaviors under
      different combustion conditions. To better understand the combustion chemistry of
      2-BTP, a theoretical study has been performed on its reactions with OH and H
      radicals. Potential energy surfaces were exhaustively explored by using B3LYP/aug
      cc-pVTZ for geometry optimizations and CCSD(T)/aug-cc-pVTZ for high level single
      point energy refinements. Detailed kinetics of the major pathways were predicted
      by using RRKM/master-equation methodology. The present predictions imply that the
      -C(Br)=CH2 moiety of 2-BTP is most likely to be responsible for its fuel-like
      property. For 2-BTP + OH, the addition to the initial adduct (CF3CBrCH2OH) is the
      dominant channel at low temperatures, while the substitution reaction (CF3COHCH2
      + Br) and H abstraction reaction (CF3CBrCH + H2O) dominates at high temperatures
      and elevated pressures. For 2-BTP + H, the addition to the initial adduct
      (CF3CBrCH3) also dominates the overall kinetics at low temperatures, while Br
      abstraction reaction (CF3CCH2 + HBr) and beta-scission of the adduct forming
      CF3CHCH2 + Br dominates at high temperatures and elevated pressures. Compared to
      2-BTP + OH, the 2-BTP + H reaction tends to have a larger effect on flame
      suppression, given the fact that it produces more inhibition species.

PMID- 29210997
TI  - Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities
      in mdx Mice.
AB  - Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness,
      cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as
      a secondary pathology in DMD, the efficacy of antioxidant intervention, using the
      superoxide scavenger tempol, was examined on functional and biochemical status of
      dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex
      vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without
      a 14-day antioxidant intervention. The enzymatic activities of muscle citrate
      synthase, phosphofructokinase, and lactate dehydrogenase were assessed using
      spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction
      and altered biochemical status. Chronic tempol supplementation in the drinking
      water increased diaphragm functional capacity and citrate synthase and lactate
      dehydrogenase enzymatic activities, restoring all values to wild-type levels.
      Chronic supplementation with tempol recovers force-generating capacity and
      metabolic enzyme activity in mdx diaphragm. These findings may have relevance in
      the search for therapeutic strategies in neuromuscular disease.

PMID- 29210998
TI  - Investigation of 'Head-to-Tail'-Connected Oligoaryl N,O-Ligands as Recognition
      Motifs for Cancer-Relevant G-Quadruplexes.
AB  - Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings,
      introduce useful and tunable properties as alternative ligands for biomolecular
      recognition. In this study, we have explored a synthetic scheme relying on Van
      Leusen oxazole formation, in conjunction with C-H activation of the formed
      oxazoles and their subsequent C-C cross-coupling to 2-bromopyridines in order to
      assemble a library of variable-length, 'head-to-tail'-connected, pyridyl-oxazole
      ligands. Through investigation of the interaction of the three longer ligands (5
      mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human
      telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl
      oxazole motif has been demonstrated to be a prominent recognition element for G
      quadruplexes. Fluorescence titrations reveal excellent binding affinities of the
      7-mer and 6-mer for a Na+-induced antiparallel 22AG G-quadruplex (KD = 0.6 * 10-7
      M-1 and 0.8 * 10-7 M-1, respectively), and satisfactory (albeit lower) affinities
      for the 22AG/K+ and Myc2345-Pu22/K+ G-quadruplexes. All ligands tested exhibit
      substantial selectivity for G-quadruplex versus duplex (ds26) DNA, as evidenced
      by competitive Forster resonance energy transfer (FRET) melting assays.
      Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology
      transition of 22AG/K+ G-quadruplex.

PMID- 29211000
TI  - Evaluation of the Corrosion Resistance Properties of Electroplated Chitosan-Zn1
      xCuxO Composite Thin Films.
AB  - Novel chitosan-zinc copper oxide (Zn1-xCuxO) composites were electrochemically
      synthesized through galvanostatic deposition. The prepared chitosan-based
      composite thin films were elaborately investigated to determine their structural,
      morphological, compositional, impedance, and corrosion properties. X-ray
      diffraction analysis was performed to reveal their structural orientation of
      composite thin films. Energy dispersive analysis by X-ray evidently confirmed the
      existence of Zn, Cu, and O in the composite thin films. Nyquist plots revealed
      that the chitosan-Zn1-xCuxO thin films had obvious semi-circular boundaries, and
      higher resistance was observed for chitosan-ZnO due to the grain boundary effect.
      Corrosion properties were evaluated using both an electrochemical method and the
      ASTM weight gain method, which revealed good corrosion rates of 34 and 35 * 10-3
      mm/y, respectively, for chitosan-ZnO thin film.

PMID- 29211001
TI  - Exploring Determinants of Spatial Variations in the Dengue Fever Epidemic Using
      Geographically Weighted Regression Model: A Case Study in the Joint Guangzhou
      Foshan Area, China, 2014.
AB  - Dengue fever (DF) is a common and rapidly spreading vector-borne viral disease in
      tropical and subtropical regions. In recent years, this imported disease has
      posed an increasing threat to public health in China, especially in many southern
      cities. Although the severity of DF outbreaks in these cities is generally
      associated with known risk factors at various administrative levels, spatial
      heterogeneities of these associations remain little understood on a finer scale.
      In this study, the neighboring Guangzhou and Foshan (GF) cities were considered
      as a joint area for characterizing the spatial variations in the 2014 DF epidemic
      at various grid levels from 1 * 1 km2 to 6 * 6 km2. On an appropriate scale,
      geographically weighted regression (GWR) models were employed to interpret the
      influences of socioeconomic and environmental factors on this epidemic across the
      GF area. DF transmissions in Guangzhou and Foshan cities presented synchronous
      temporal changes and spatial expansions during the main epidemic months. Across
      the GF area, this epidemic was obviously spatially featured at various grid
      levels, especially on the 2 * 2 km2 scale. Its spatial variations were relatively
      sufficiently explained by population size, road density, and economic status
      integrated in the GWR model with the lowest Akaike Information Criterion (AICc =
      5227.97) and highest adjusted R square (0.732) values. These results indicated
      that these three socioeconomic factors acted as geographical determinants of
      spatial variability of the 2014 DF epidemic across the joint GF area, although
      some other potential factors should be added to improve the explaining the
      spatial variations in the central zones. This work improves our understanding of
      the effects of socioeconomic conditions on the spatial variations in this
      epidemic and helps local hygienic authorities to make targeted joint
      interventions for preventing and controlling this epidemic across the GF area.

PMID- 29210999
TI  - Adverse Intrauterine Environment and Cardiac miRNA Expression.
AB  - Placental insufficiency, high altitude pregnancies, maternal obesity/diabetes,
      maternal undernutrition and stress can result in a poor setting for growth of the
      developing fetus. These adverse intrauterine environments result in physiological
      changes to the developing heart that impact how the heart will function in
      postnatal life. The intrauterine environment plays a key role in the complex
      interplay between genes and the epigenetic mechanisms that regulate their
      expression. In this review we describe how an adverse intrauterine environment
      can influence the expression of miRNAs (a sub-set of non-coding RNAs) and how
      these changes may impact heart development. Potential consequences of altered
      miRNA expression in the fetal heart include; Hypoxia inducible factor (HIF)
      activation, dysregulation of angiogenesis, mitochondrial abnormalities and
      altered glucose and fatty acid transport/metabolism. It is important to
      understand how miRNAs are altered in these adverse environments to identify key
      pathways that can be targeted using miRNA mimics or inhibitors to condition an
      improved developmental response.

PMID- 29211002
TI  - Pan-Domain Analysis of ZIP Zinc Transporters.
AB  - The ZIP (Zrt/Irt-like protein) family of zinc transporters is found in all three
      domains of life. However, little is known about the phylogenetic relationship
      amongst ZIP transporters, their distribution, or their origin. Here we employed
      phylogenetic analysis to explore the evolution of ZIP transporters, with a focus
      on the major human fungal pathogen, Candida albicans. Pan-domain analysis of
      bacterial, archaeal, fungal, and human proteins revealed a complex relationship
      amongst the ZIP family members. Here we report (i) a eukaryote-wide group of
      cellular zinc importers, (ii) a fungal-specific group of zinc importers having
      genetic association with the fungal zincophore, and, (iii) a pan-kingdom
      supercluster made up of two distinct subgroups with orthologues in bacterial,
      archaeal, and eukaryotic phyla.

PMID- 29211003
TI  - Metabolites with Insecticidal Activity from Aspergillus fumigatus JRJ111048
      Isolated from Mangrove Plant Acrostichum specioum Endemic to Hainan Island.
AB  - Fungi residing in mangroves are considered to be a bank of novel bioactive
      natural products. In the screening for bioactive metabolites from mangrove
      derived fungi, the ethyl acetate extract of the fermentation broth of Aspergillus
      fumigatus JRJ111048, a fungus isolated from the leaves of the mangrove plant
      Acrostichum specioum endemic to Hainan island, was found to possess insecticidal
      activity against Spodoptera litura. Bioactivity-guided isolation lead to the
      discovery of seven metabolites 1-7, including one new anhydride derivative
      aspergide (1), one new lipid amide 11-methyl-11-hydroxyldodecanoic acid amide
      (2), and five known compounds; alpha-ethyl glucoside (3), spiculisporic acid B
      (4), spiculisporic acid C (5), spiculisporic acid (6), and secospiculisporic acid
      B (7). Their structures were established by NMR spectroscopic and MS analyses,
      and by comparison of previously reported data. Insecticidal activity against S.
      litura and antifungal activity of these compounds were investigated. As a result,
      the new compound 1 showed potent insecticidal activity against newly hatched
      larvae of S. litura, and compound 4 displayed weak antifungal activity against
      Candida albicans.

PMID- 29211004
TI  - A "Skylight" Simulator for HWIL Simulation of Hyperspectral Remote Sensing.
AB  - Even though digital simulation technology has been widely used in the last two
      decades, hardware-in-the-loop (HWIL) simulation is still an indispensable method
      for spectral uncertainty research of ground targets. However, previous facilities
      mainly focus on the simulation of panchromatic imaging. Therefore, neither the
      spectral nor the spatial performance is enough for hyperspectral simulation. To
      improve the accuracy of illumination simulation, a new dome-like skylight
      simulator is designed and developed to fit the spatial distribution and spectral
      characteristics of a real skylight for the wavelength from 350 nm to 2500 nm. The
      simulator's performance was tested using a spectroradiometer with different
      accessories. The spatial uniformity is greater than 0.91. The spectral mismatch
      decreases to 1/243 of the spectral mismatch of the Imagery Simulation Facility
      (ISF). The spatial distribution of radiance can be adjusted, and the accuracy of
      the adjustment is greater than 0.895. The ability of the skylight simulator is
      also demonstrated by comparing radiometric quantities measured in the skylight
      simulator with those in a real skylight in Beijing.

PMID- 29211005
TI  - Isolation of Petrocidin A, a New Cytotoxic Cyclic Dipeptide from the Marine
      Sponge-Derived Bacterium Streptomyces sp. SBT348.
AB  - A new cyclic dipeptide, petrocidin A (1), along with three known compounds-2,3
      dihydroxybenzoic acid (2), 2,3-dihydroxybenzamide (3), and maltol (4)-were
      isolated from the solid culture of Streptomyces sp. SBT348. The strain
      Streptomyces sp. SBT348 had been prioritized in a strain collection of 64 sponge
      associated actinomycetes based on its distinct metabolomic profile using liquid
      chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic
      resonance (NMR). The absolute configuration of all alpha-amino acids was
      determined by HPLC analysis after derivatization with Marfey's reagent and
      comparison with commercially available reference amino acids. Structure
      elucidation was pursued in the presented study by mass spectrometry and NMR
      spectral data. Petrocidin A (1) and 2,3-dihydroxybenzamide (3) exhibited
      significant cytotoxicity towards the human promyelocytic HL-60 and the human
      colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential
      of sponge-associated actinomycetes for the discovery of novel and
      pharmacologically active natural products.

PMID- 29211006
TI  - Laser-Induced Breakdown Spectroscopy (LIBS) for Monitoring the Formation of
      Hydroxyapatite Porous Layers.
AB  - Laser-induced breakdown spectroscopy (LIBS) is applied to characterize the
      formation of porous hydroxyapatite layers on the surface of 0.8CaSiO3
      0.2Ca3(PO4)2 biocompatible eutectic glass immersed in simulated body fluid (SBF).
      Compositional and structural characterization analyses were also conducted by
      field emission scanning electron microscopy (FESEM), energy dispersive X-ray
      spectroscopy (EDX), and micro-Raman spectroscopy.

PMID- 29211007
TI  - Contribution of Dietary Supplements to Nutritional Adequacy in Various Adult Age
      Groups.
AB  - Many Americans have inadequate intakes of several nutrients. The Dietary
      Guidelines for Americans 2015-2020 specifically identified vitamins A, C, D and
      E, calcium, magnesium, iron, potassium, choline and fiber as "underconsumed
      nutrients". Based on nationally representative data in 10,698 adults from
      National Health and Nutrition Examination Surveys (NHANES), 2009-2012,
      assessments were made of age-group differences in the impact of dietary
      supplements on nutrient intake and inadequacies. Compared to food alone, use of
      any dietary supplement plus food was associated with significantly (p < 0.01)
      higher intakes of 15-16 of 19 nutrients examined in all age groups; and
      significantly reduced rates of inadequacy for 10/17, 8/17 and 6/17 nutrients
      examined among individuals age >=71, 51-70 and 19-50 years, respectively.
      Compared to the other age groups, older adults (>=71 years) had lower rates of
      inadequacy for iron and vitamins A, C, D and E, but higher rates for calcium. An
      increased prevalence of intakes above the Tolerable Upper Intake Level was seen
      for 8-9 of 13 nutrients, but were mostly less than 5% of the population. In
      conclusion, dietary supplement use is associated with increased micronutrient
      intake, decreased inadequacies, and slight increases in prevalence above the UL,
      with greater benefits seen among older adults.

PMID- 29211008
TI  - Sociodemographic Factors on Contraceptive Use among Ever-Married Women of
      Reproductive Age: Evidence from Three Demographic and Health Surveys in
      Bangladesh.
AB  - Contraceptive use among married women of reproductive age has showed a
      substantial progress over the last few decades in Bangladesh. This study explores
      the sociodemographic factors associated with contraceptive use among ever-married
      women of reproductive age in Bangladesh by utilizing the information extracted
      from three of the Bangladesh Demographic and Health Surveys (BDHSs) in 1993-1994,
      2004 and 2014. Bivariate analysis was conducted by performing chi-squared test of
      independence to explore the relationship between selected sociodemographic
      factors and dependent variables. To know the adjusted effects of covariates, a
      popular binary logistic regression model was considered. Respondents' current
      age, place residence, division religion, education, age at first marriage, family
      planning (FP) media exposure, ideal number of children and fertility preferences
      are the significant determinants according to the most recent survey, BDHS 2014.
      However, wealth index and a respondent's current working status were found to be
      significant factors only in BDHS 2004. The results of the study strongly
      recommend efforts to increase the education level among poor people, particularly
      among women in Bangladesh. Program interventions, including health behavior
      education and family planning services and counselling, are especially needed for
      some categories of the population, including those living in rural areas, Sylhet,
      Chittagong and Dhaka divisions, as well as illiterate and Muslim ever-married
      women.

PMID- 29211009
TI  - Selection of Meat Inspection Data for an Animal Welfare Index in Cattle and Pigs
      in Denmark.
AB  - National welfare indices of cattle and pigs are constructed in Denmark, and meat
      inspection data may be used to contribute to these. We select potentially welfare
      relevant abattoir recordings and assess the sources of variation within these
      with a view towards inclusion in the indices. Meat inspection codes were pre
      selected based on expert judgement of having potential animal welfare relevance.
      Random effects logistic regression was then used to determine the magnitude of
      variation derived at the level of the farm or abattoir, of which farm variation
      might be associated with welfare, whereas abattoir variation is most likely
      caused by differences in recording practices. Codes were excluded for use in the
      indices based on poor model fit or a large abattoir effect. There was a large
      abattoir effect for most of the codes modelled and these codes were deemed to be
      not appropriate to be carried forward to the welfare index. A few were found to
      be potentially useful for a welfare index: Eight for slaughter pigs, 15 for sows,
      five for cattle <18 months of age, and six for older cattle. The absolute
      accuracy of each code/combination could not be assessed, only the relative
      variation between farms and abattoirs.

PMID- 29211011
TI  - Chemical Stability between NiCr2O4 Material and Molten Calcium-Magnesium-Alumino
      Silicate (CMAS) at High Temperature.
AB  - NiCr2O4 as a potential protection for thermal barrier coatings (TBCs) against the
      attack of molten calcium-magnesium-alumino-silicate (CMAS) was studied by a CMAS
      contacting experiment. Atmospheric plasma sprayed coatings and sintered bulk
      materials were fabricated, covered with CMAS deposits, and exposed to 1200 
      degrees C for 24 h. Nano-sized CMAS-NiCr2O4 mixed powder was manufactured by ball
      milling and then conducted heat treatment under the same condition. The results
      show that no reacting product was found at the border between molten CMAS and
      NiCr2O4 and no element transportation occurred. It can be inferred that NiCr2O4
      has outstanding chemical stability with the molten CMAS.

PMID- 29211010
TI  - Meta-Analysis of Fecal Microbiota and Metabolites in Experimental Colitic Mice
      during the Inflammatory and Healing Phases.
AB  - The imbalance of gut microbiota is known to be associated with inflammatory bowel
      disease, but it remains unknown whether dysbiosis is a cause or consequence of
      chronic gut inflammation. In order to investigate the effects of gut inflammation
      on microbiota and metabolome, the sequential changes in gut microbiota and
      metabolites from the onset of colitis to the recovery in dextran sulfate sodium
      induced colitic mice were characterized by using meta 16S rRNA sequencing and
      proton nuclear magnetic resonance (1H-NMR) analysis. Mice in the colitis
      progression phase showed the transient expansions of two bacterial families
      including Bacteroidaceae and Enterobacteriaceae and the depletion of major gut
      commensal bacteria belonging to the uncultured Bacteroidales family S24-7,
      Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. After the initiation of the
      recovery, commensal Lactobacillus members promptly predominated in gut while
      other normally abundant bacteria excluding the Erysipelotrichaceae remained
      diminished. Furthermore, 1H-NMR analysis revealed characteristic fluctuations in
      fecal levels of organic acids (lactate and succinate) associated with the disease
      states. In conclusion, acute intestinal inflammation is a perturbation factor of
      gut microbiota but alters the intestinal environments suitable for Lactobacillus
      members.

PMID- 29211012
TI  - Comparative Analysis of the Nitrogen Effect of Common Agricultural Practices and
      Rotation Systems in a Rainfed Mediterranean Environment.
AB  - The nitrogen (N) effect of legumes is one of the main reasons for their inclusion
      in rotation systems and their success in rainfed agriculture of Mediterranean
      areas. The comparative analysis of this effect in relation to alternative systems
      or practices is essential for a comprehensive appreciation in their merit. This
      field experiment was comprised of four three-year rotation cycles. Wheat
      (Triticum turgidum durum) was seeded for two consecutive years after common vetch
      (Vicia sativa L.), treated in three different ways, and after fallow and compared
      with three wheat monocultures: the conventional one, the continuous straw
      incorporation, and the sewage sludge incorporation once every three years. Wheat
      grain and straw yields and N uptake were compared among treatments. Results
      showed that rotation systems that included vetch were the most promising for
      improving sustainability. Maximum N uptake and the greatest yield surpluses were
      obtained when wheat followed vetch incorporated during flowering. When vetch in
      the rotation was cut for hay or left to fill grains subsequent wheat showed also
      enhanced yields. Fallow affected the rotation system's fertility due to the
      incorporation of volunteer plants into the soil. Sewage sludge sustained
      production without the need for inorganic fertilization during three years. Straw
      incorporation always gave the smallest yields and N harvests, presumably due to
      soil N immobilization.

PMID- 29211013
TI  - Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a
      Selective S1P1 Receptor Modulator in Healthy Subjects.
AB  - The pharmacokinetics, pharmacodynamics, tolerability, and food effect of
      cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were
      investigated in three sub-studies. Two double-blind, placebo-controlled,
      randomised studies in healthy male subjects were performed. Cenerimod was
      administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for
      35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study
      was performed to assess the food effect (1 mg, Study 3). The pharmacokinetic
      profile of cenerimod was characterised by a tmax of 5.0-6.2 h. Terminal half-life
      after single and multiple doses ranged from 170 to 199 h and 283 to 539 h,
      respectively. Food had no relevant effect on the pharmacokinetics of cenerimod. A
      dose-dependent decrease in lymphocyte count was observed after initiation of
      cenerimod and reached a plateau (maximum change from baseline: -64%) after 20-23
      days of treatment. Lymphocyte counts returned to baseline values at end-of-study
      examination. One serious adverse event of circulatory collapse (25 mg dose group,
      maximum tolerated dose: 10 mg) and adverse events of mild-to-moderate intensity
      were reported. Treatment initiation was associated with transient decreases in
      heart rate and blood pressure at doses >1 and >=10 mg, respectively.

PMID- 29211015
TI  - The Effect of Electrical Impedance Matching on the Electromechanical
      Characteristics of Sandwiched Piezoelectric Ultrasonic Transducers.
AB  - For achieving the power maximum transmission, the electrical impedance matching
      (EIM) for piezoelectric ultrasonic transducers is highly required. In this paper,
      the effect of EIM networks on the electromechanical characteristics of sandwiched
      piezoelectric ultrasonic transducers is investigated in time and frequency
      domains, based on the PSpice model of single sandwiched piezoelectric ultrasonic
      transducer. The above-mentioned EIM networks include, series capacitance and
      parallel inductance (I type) and series inductance and parallel capacitance (II
      type). It is shown that when I and II type EIM networks are used, the resonance
      and anti-resonance frequencies and the received signal tailing are decreased; II
      type makes the electro-acoustic power ratio and the signal tailing smaller
      whereas it makes the electro-acoustic gain ratio larger at resonance frequency.
      In addition, I type makes the effective electromechanical coupling coefficient
      increase and II type makes it decrease; II type make the power spectral density
      at resonance frequency more dramatically increased. Specially, the electro
      acoustic power ratio has maximum value near anti-resonance frequency, while the
      electro-acoustic gain ratio has maximum value near resonance frequency. It can be
      found that the theoretically analyzed results have good consistency with the
      measured ones.

PMID- 29211014
TI  - Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine
      Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b.
AB  - Sepsis is an overwhelming systemic response to infection that frequently results
      in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin
      E2 (PGE2), and cytokine overproduction are thought to be associated with the
      immunostimulatory cascade in sepsis. In the present study, we analyzed the anti
      inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and
      purified human CD14+ monocytes stimulated with lipopolysaccharide (LPS) and
      elucidated the mechanisms by analyzing the cell signaling pathways known to be
      activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and
      cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also
      reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO,
      PGE2, and cytokine overproduction arose from the suppression of STAT-1 and
      PI3K/Akt pathways; no changes in NF-kappaB, MAPK, and AP-1 signaling were
      detected. Thus, pheophytin-b may represent a potential candidate to beneficially
      modulate the inflammatory response in sepsis.

PMID- 29211017
TI  - Sliding Mode Observer-Based Current Sensor Fault Reconstruction and Unknown Load
      Disturbance Estimation for PMSM Driven System.
AB  - This paper proposes a new scheme of reconstructing current sensor faults and
      estimating unknown load disturbance for a permanent magnet synchronous motor
      (PMSM)-driven system. First, the original PMSM system is transformed into two
      subsystems; the first subsystem has unknown system load disturbances, which are
      unrelated to sensor faults, and the second subsystem has sensor faults, but is
      free from unknown load disturbances. Introducing a new state variable, the
      augmented subsystem that has sensor faults can be transformed into having
      actuator faults. Second, two sliding mode observers (SMOs) are designed: the
      unknown load disturbance is estimated by the first SMO in the subsystem, which
      has unknown load disturbance, and the sensor faults can be reconstructed using
      the second SMO in the augmented subsystem, which has sensor faults. The gains of
      the proposed SMOs and their stability analysis are developed via the solution of
      linear matrix inequality (LMI). Finally, the effectiveness of the proposed scheme
      was verified by simulations and experiments. The results demonstrate that the
      proposed scheme can reconstruct current sensor faults and estimate unknown load
      disturbance for the PMSM-driven system.

PMID- 29211016
TI  - Expression Profiling of Autophagy Genes BxATG1 and BxATG8 under Biotic and
      Abiotic Stresses in Pine Wood Nematode Bursaphelenchus xylophilus.
AB  - The pine wood nematode (PWN), Bursaphelenchusxylophilus, is the pathogen of pine
      wilt disease (PWD) and causes huge economic losses in pine forests and shows a
      remarkable ability to survive under unfavorable and changing environmental
      conditions. This ability may be related to autophagy, which is still poorly
      understood in B.xylophilus. Our previous studies showed that autophagy exists in
      PWN. Therefore, we tested the effects of autophagy inducer rapamycin on PWN and
      the results revealed that the feeding rate and reproduction were significantly
      promoted on fungal mats. The gene expression patterns of BxATG1 and BxATG8 under
      the different stress were determined by quantitative reverse transcription PCR
      (qRT-PCR). We tested the effects of RNA interference on BxATG1 and BxATG8 in PWN
      during different periods of infection in Pinus thunbergii. The results revealed
      that BxATG1 and BxATG8 may play roles in allowing PWN to adapt to changing
      environmental conditions and the virulence of PWN was influenced by the silence
      of autophagy-related genes BxATG1 and BxATG8. These results provided fundamental
      information on the relationship between autophagy and PWN, and on better
      understanding of gene function of BxATG1 and BxATG8 in PWN.

PMID- 29211018
TI  - Parameter Search Algorithms for Microwave Radar-Based Breast Imaging: Focal
      Quality Metrics as Fitness Functions.
AB  - Inaccurate estimation of average dielectric properties can have a tangible impact
      on microwave radar-based breast images. Despite this, recent patient imaging
      studies have used a fixed estimate although this is known to vary from patient to
      patient. Parameter search algorithms are a promising technique for estimating the
      average dielectric properties from the reconstructed microwave images themselves
      without additional hardware. In this work, qualities of accurately reconstructed
      images are identified from point spread functions. As the qualities of accurately
      reconstructed microwave images are similar to the qualities of focused
      microscopic and photographic images, this work proposes the use of focal quality
      metrics for average dielectric property estimation. The robustness of the
      parameter search is evaluated using experimental dielectrically heterogeneous
      phantoms on the three-dimensional volumetric image. Based on a very broad initial
      estimate of the average dielectric properties, this paper shows how these metrics
      can be used as suitable fitness functions in parameter search algorithms to
      reconstruct clear and focused microwave radar images.

PMID- 29211019
TI  - Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to
      Antibiotic Stress in Escherichia coli.
AB  - Antibiotic resistant Gram-negative bacteria are a serious threat for public
      health. The permeation of antibiotics through their outer membrane is largely
      dependent on porin, changes in which cause reduced drug uptake and efficacy.
      Escherichia coli produces two major porins, OmpF and OmpC. MicF and MicC are
      small non-coding RNAs (sRNAs) that modulate the expression of OmpF and OmpC,
      respectively. In this work, we investigated factors that lead to increased
      production of MicC. micC promoter region was fused to lacZ, and the reporter
      plasmid was transformed into E. coli MC4100 and derivative mutants. The response
      of micC-lacZ to antimicrobials was measured during growth over a 6 h time period.
      The data showed that the expression of micC was increased in the presence of beta
      lactam antibiotics and in an rpoE depleted mutant. Interestingly, the same
      conditions enhanced the activity of an ompN-lacZ fusion, suggesting a dual
      transcriptional regulation of micC and the quiescent adjacent ompN. Increased
      levels of OmpN in the presence of sub-inhibitory concentrations of chemicals
      could not be confirmed by Western blot analysis, except when analyzed in the
      absence of the sigma factor sigmaE. We suggest that the MicC sRNA acts together
      with the sigmaE envelope stress response pathway to control the OmpC/N levels in
      response to beta-lactam antibiotics.

PMID- 29211020
TI  - An Updated View of Translocator Protein (TSPO).
AB  - Decades of study on the role of mitochondria in living cells have evidenced the
      importance of the 18 kDa mitochondrial translocator protein (TSPO), first
      discovered in the 1977 as an alternative binding site for the benzodiazepine
      diazepam in the kidneys. This protein participates in a variety of cellular
      functions, including cholesterol transport, steroid hormone synthesis,
      mitochondrial respiration, permeability transition pore opening, apoptosis, and
      cell proliferation. Thus, TSPO has become an extremely attractive subcellular
      target for the early detection of disease states that involve the overexpression
      of this protein and the selective mitochondrial drug delivery. This special issue
      was programmed with the aim of summarizing the latest findings about the role of
      TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or
      therapeutics. A total of 9 papers have been accepted for publication in this
      issue, in particular, 2 reviews and 7 primary data manuscripts, overall
      describing the main advances in this field.

PMID- 29211021
TI  - Challenging Notions of Academic Entitlement and Its Rise among Liberal Arts
      College Students.
AB  - To assess academic entitlement, we employed a repeated cross-sectional design to
      compare survey data from two systematic random samples collected eight years
      apart, in 2009 (n = 225) and 2017 (n = 159), at a small, private, mid-Atlantic
      liberal arts college. According to an entitlement scale (based on Greenberger et
      al., 2008), students were less likely to be entitled in 2017 (27%) than in 2009
      (41%) (p = 0.02). In 2009, a higher proportion of males than females felt
      entitled (50% versus 34%, p = 0.05), a sex difference that disappeared by 2017.
      To explore academic entitlement further, we developed the "PIE" scale to measure
      the extent to which students believe "participation," "improvement" and "effort"
      should help determine their course grades. Although the proportion of above
      average PIE scorers was stable from 2009 (36%) to 2017 (34%), in 2017, more
      females than males were above average on PIE (26% of males versus 44% of females,
      p = 0.02). PIE, or the desire for recognition of "academic sweat equity," could
      reflect students' support for a learning model that goes beyond mastery and is
      more developmental and process oriented. These data challenge common conceptions
      of what constitutes academic entitlement, the belief that it is rising, and
      suggest continued discussions of what factors should determine grades.

PMID- 29211022
TI  - Tracking Functional Tumor Cell Subpopulations of Malignant Glioma by Phasor
      Fluorescence Lifetime Imaging Microscopy of NADH.
AB  - Intra-tumoral heterogeneity is associated with therapeutic resistance of cancer
      and there exists a need to non-invasively identify functional tumor
      subpopulations responsible for tumor recurrence. Reduced nicotinamide adenine
      dinucleotide (NADH) is a metabolic coenzyme essential in cellular respiration.
      Fluorescence lifetime imaging microscopy (FLIM) of NADH has been demonstrated to
      be a powerful label-free indicator for inferring metabolic states of living
      cells. Using FLIM, we identified a significant shift towards longer NADH
      fluorescence lifetimes, suggesting an increase in the fraction of protein-bound
      NADH, in the invasive stem-like tumor-initiating cell (STIC) subpopulation
      relative to the tumor mass-forming cell (TMC) subpopulation of malignant gliomas.
      By applying our previously studied model to transition glioma from a majority of
      STIC to a majority of TMC in serum-adherent culture conditions following serial
      passages, we compared changes in NADH states, cellular respirations (oxidative
      phosphorylation and glycolysis), EGFR expression, and cell-growth speed over
      passages. We identified a significant positive correlation between free-NADH
      fraction and cell growth, which was related to an increase of TMC fraction. In
      comparison, the increase of EGFR and cellular respirations preceded all these
      changes. In conclusion, FLIM of NADH provides a non-invasive method to monitor
      the dynamics of tumor heterogeneity before and after treatment.

PMID- 29211023
TI  - Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization
      and Targeted Drug Delivery.
AB  - Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the
      induction of acute phase protein biosynthesis. Further to its central role in
      many aspects of the immune system, IL-6 regulates a variety of homeostatic
      processes. To interfere with IL-6 dependent diseases, such as various autoimmune
      diseases or certain cancers like multiple myeloma or hepatocellular carcinoma
      associated with chronic inflammation, it might be a sensible strategy to target
      human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have
      selected and characterized different DNA and RNA aptamers specifically binding IL
      6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling
      pathway but are internalized with the receptor and thus can serve as vehicles for
      the delivery of different cargo molecules like therapeutics. We succeeded in the
      construction of a chlorin e6 derivatized aptamer to be delivered for targeted
      photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer
      intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted
      chemotherapy. The alpha6beta4 integrin specific DNA aptamer IDA, also selected in
      our laboratory is internalized, too. All these aptamers can serve as vehicles for
      targeted drug delivery into cells. We call them charomers-in memory of Charon,
      the ferryman in Greek mythology, who ferried the deceased into the underworld.

PMID- 29211025
TI  - Bearing Fault Diagnosis under Variable Speed Using Convolutional Neural Networks
      and the Stochastic Diagonal Levenberg-Marquardt Algorithm.
AB  - This paper presents a novel method for diagnosing incipient bearing defects under
      variable operating speeds using convolutional neural networks (CNNs) trained via
      the stochastic diagonal Levenberg-Marquardt (S-DLM) algorithm. The CNNs utilize
      the spectral energy maps (SEMs) of the acoustic emission (AE) signals as inputs
      and automatically learn the optimal features, which yield the best discriminative
      models for diagnosing incipient bearing defects under variable operating speeds.
      The SEMs are two-dimensional maps that show the distribution of energy across
      different bands of the AE spectrum. It is hypothesized that the variation of a
      bearing's speed would not alter the overall shape of the AE spectrum rather, it
      may only scale and translate it. Thus, at different speeds, the same defect would
      yield SEMs that are scaled and shifted versions of each other. This hypothesis is
      confirmed by the experimental results, where CNNs trained using the S-DLM
      algorithm yield significantly better diagnostic performance under variable
      operating speeds compared to existing methods. In this work, the performance of
      different training algorithms is also evaluated to select the best training
      algorithm for the CNNs. The proposed method is used to diagnose both single and
      compound defects at six different operating speeds.

PMID- 29211024
TI  - Engineering the l-Arabinose Isomerase from Enterococcus Faecium for d-Tagatose
      Synthesis.
AB  - l-Arabinose isomerase (EC 5.3.1.4) (l-AI) from Enterococcus faecium DBFIQ E36 was
      overproduced in Escherichia coli by designing a codon-optimized synthetic araA
      gene. Using this optimized gene, two N- and C-terminal His-tagged-l-AI proteins
      were produced. The cloning of the two chimeric genes into regulated expression
      vectors resulted in the production of high amounts of recombinant N-His-l-AI and
      C-His-l-AI in soluble and active forms. Both His-tagged enzymes were purified in
      a single step through metal-affinity chromatography and showed different kinetic
      and structural characteristics. Analytical ultracentrifugation revealed that C
      His-l-AI was preferentially hexameric in solution, whereas N-His-l-AI was mainly
      monomeric. The specific activity of the N-His-l-AI at acidic pH was higher than
      that of C-His-l-AI and showed a maximum bioconversion yield of 26% at 50  degrees
      C for d-tagatose biosynthesis, with Km and Vmax parameters of 252 mM and 0.092 U
      mg-1, respectively. However, C-His-l-AI was more active and stable at alkaline pH
      than N-His-l-AI. N-His-l-AI follows a Michaelis-Menten kinetic, whereas C-His-l
      AI fitted to a sigmoidal saturation curve.

PMID- 29211026
TI  - A Review of Chronic Pain and Cognitive, Mood, and Motor Dysfunction Following
      Mild Traumatic Brain Injury: Complex, Comorbid, and/or Overlapping Conditions?
AB  - Mild traumatic brain injury (mTBI) is commonly encountered in clinical practice.
      While the cognitive ramifications of mTBI are frequently described in the
      literature, the impact of mTBI on emotional, sensory, and motor function is not
      as commonly discussed. Chronic pain is a phenomenon more prevalent among patients
      with mTBI compared to those with moderate or severe traumatic brain injury.
      Chronic pain can become a primary disorder of the central nervous system (CNS)
      expressed as widespread pain, and cognitive, mood, and movement dysfunction.
      Shared mechanisms across chronic pain conditions can account for how pain is
      generated and maintained in the CNS, irrespective of the underlying structural
      pathology. Herein, we review the impact of mTBI on cognitive, emotional, sensory,
      and motor domains, and the role of pain as an important confounding variable in
      patient recovery and dysfunction following mTBI.

PMID- 29211027
TI  - Dietary Intake of Protein from Different Sources and Weight Regain, Changes in
      Body Composition and Cardiometabolic Risk Factors after Weight Loss: The DIOGenes
      Study.
AB  - An increase in dietary protein intake has been shown to improve weight loss
      maintenance in the DIOGenes trial. Here, we analysed whether the source of the
      dietary proteins influenced changes in body weight, body composition, and
      cardiometabolic risk factors during the weight maintenance period while following
      an energy-restricted diet. 489 overweight or obese participants of the DIOGenes
      trial from eight European countries were included. They successfully lost >8% of
      body weight and subsequently completed a six month weight maintenance period, in
      which they consumed an ad libitum diet varying in protein content and glycemic
      index. Dietary intake was estimated from three-day food diaries. A higher plant
      protein intake with a proportional decrease in animal protein intake did not
      affect body weight maintenance or cardiometabolic risk factors. A higher plant
      protein intake from non-cereal products instead of cereal products was associated
      with benefits for body weight maintenance and blood pressure. Substituting meat
      protein for protein from other animal sources increased insulin and HOMA-IR
      (homeostasis model assessment of insulin resistance). This analysis suggests that
      not only the amount of dietary proteins, but also the source may be important for
      weight and cardiometabolic risk management. However, randomized trials are needed
      to test the causality of these associations.

PMID- 29211028
TI  - Effect of Electron Blocking Layer Doping and Composition on the Performance of
      310 nm Light Emitting Diodes.
AB  - The effects of composition and p-doping profile of the AlGaN:Mg electron blocking
      layer (EBL) in 310 nm ultraviolet B (UV-B) light emitting diodes (LEDs) have been
      investigated. The carrier injection and internal quantum efficiency of the LEDs
      were simulated and compared to electroluminescence measurements. The light output
      power depends strongly on the temporal biscyclopentadienylmagnesium (Cp 2 Mg)
      carrier gas flow profile during growth as well as on the aluminum profile of the
      AlGaN:Mg EBL. The highest emission power has been found for an EBL with the
      highest Cp 2 Mg carrier gas flow and a gradually decreasing aluminum content in
      direction to the p-side of the LED. This effect is attributed to an improved
      carrier injection and confinement that prevents electron leakage into the p-doped
      region of the LED with a simultaneously enhanced carrier injection into the
      active region.

PMID- 29211029
TI  - Generalized Fracture Toughness and Compressive Strength of Sustainable Concrete
      Including Low Calcium Fly Ash.
AB  - The paper presents the results of tests on the effect of the low calcium fly ash
      (LCFA) addition, in the amounts of: 0% (LCFA-00), 20% (LCFA-20) and 30% (LCFA-30)
      by weight of cement, on fracture processes in structural concretes. In the course
      of the experiments, compressive strength of concrete and fracture toughness for:
      I (tensile), II (in-plane shear) and III (anti-plane shear) models of cracking
      were measured. The tests determined the effect of age of concretes modified with
      LCFA on the analyzed parameters. The experiments were carried out after: 3, 7,
      28, 90, 180 and 365 days of curing. Fracture toughness of concretes was
      determined in terms of the critical stress intensity factors: K I c S , K I I c ,
      K I I I c and then a generalized fracture toughness K c was specified. The
      obtained results are significant for the analysis of concrete structures
      subjected to complex loading. The properties of composites with the additive of
      LCFA depend on the age of the concrete tested. Mature concretes exhibit high
      fracture toughness at 20% additive of LCFA, while the additive of LCFA in the
      amount of 30% weight of cement has a beneficial effect on the parameters of
      concrete only after half a year of curing.

PMID- 29211030
TI  - Thymbra capitata (L.) Cav. and Rosmarinus officinalis (L.) Essential Oils: In
      Vitro Effects and Toxicity on Swine Spermatozoa.
AB  - Essential oils possess a variety of biological properties (i.e., antioxidant,
      antibacterial, and cytotoxic) that could possibly be applied in reproductive
      medicine, but their effects on spermatozoa are still partially unknown. The aim
      of the study was to describe the effects of Thymbra capitata (L.) Cav. and
      Rosmarinus officinalis (L.) essential oils on the main morpho-functional
      parameters of swine spermatozoa. Essential oils were preliminary characterized by
      gas chromatography and added with emulsifiers to facilitate diffusion.
      Experimental samples were prepared by suspending a fixed number of spermatozoa in
      5 mL of medium with 10 different concentrations of essential oil (0.2-2 mg/mL, at
      intervals of 0.2). After 3 h of incubation, samples were analyzed for pH,
      viability, objective motility, and acrosome status. Results showed that the
      effects of the essential oils are concentration-dependent and that R. officinalis
      is well tolerated up to 0.6 mg/mL. T. capitata impaired the spermatozoa starting
      from the lowest concentration, with complete spermicidal effect from 0.4 mg/mL.
      The patterns of damage, confirmed by SEM, were different and quite distinct. As
      expected, spermatozoa proved to be sensitive to external stimuli and capable of
      showing different functional patterns, providing interesting insights to the
      action/toxicity mechanisms. The results of the present work represent the first
      step towards the systematic characterization of the effects of these compounds on
      spermatozoa. This kind of studies are necessary to strengthen the idea of future
      applications of essential oils in the reproductive field due to their
      antioxidant, antibacterial, or spermicidal properties.

PMID- 29211031
TI  - Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic
      Stimulation.
AB  - Side effects on cardiac ion channels causing lethal arrhythmias are one major
      reason for drug withdrawals from the market. Field potential (FP) recording from
      cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug
      candidates in preclinical drug development, but it is currently limited to the
      spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present
      a novel optogenetic cardiotoxicity screening system suited for the parallel
      automated frequency-dependent analysis of drug effects on FP recorded from human
      induced pluripotent stem cell-derived cardiomyocytes. For the expression of the
      light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using
      virus transduction or transient mRNA transfection. Optical stimulation was
      performed with a new light-emitting diode lid for a 96-well FP recording system.
      This enabled reliable pacing at physiologically relevant heart rates and robust
      recording of FP. Thereby we detected rate-dependent effects of drugs on Na+, Ca2+
      and K+ channel function indicated by FP prolongation, FP shortening and the
      slowing of the FP downstroke component, as well as generation of
      afterdepolarisations. Taken together, we present a scalable approach for
      preclinical frequency-dependent screening of drug effects on cardiac
      electrophysiology. Importantly, we show that the recording and analysis can be
      fully automated and the technology is readily available using commercial
      products.

PMID- 29211032
TI  - Bioavailability of Bergamot (Citrus bergamia) Flavanones and Biological Activity
      of Their Circulating Metabolites in Human Pro-Angiogenic Cells.
AB  - Myeloid angiogenic cells (MACs) play a key role in endothelial repairing
      processes and functionality but their activity may be impaired by the lipotoxic
      effects of some molecules like stearic acid (SA). Among the dietary components
      potentially able to modulate endothelial function in vivo, (poly)phenolic
      compounds represent serious candidates. Here, we apply a comprehensive
      multidisciplinary approach to shed light on the prospects of Bergamot (Citrus
      bergamia), a citrus fruit rich in flavanones and other phenolic compounds, in the
      framework of lipotoxicity-induced MACs impairment. The flavanone profile of
      bergamot juice was characterized and 16 compounds were identified, with a new 3
      hydroxy-3-methylglutaryl (HMG) flavanone, isosakuranetin-7-O-neohesperidoside-6"
      O-HMG, described for the first time. Then, a pilot bioavailability study was
      conducted in healthy volunteers to assess the circulating flavanone metabolites
      in plasma and urine after consumption of bergamot juice. Up to 12 flavanone phase
      II conjugates (sulfates and glucuronides of hesperetin, naringenin and
      eriodyctiol) were detected and quantified. Finally, the effect of some of the
      metabolites identified in vivo, namely hesperetin-7-O-glucuronide, hesperetin-3'
      O-glucuronide, naringenin-7-O-glucuronide and naringenin-4'-O-glucuronide, was
      tested, at physiological concentrations, on gene expression of inflammatory
      markers and apoptosis in MACs exposed to SA. Under these conditions, naringenin
      4'-O-glucuronide and hesperetin-7-O-glucuronide were able to modulate
      inflammation, while no flavanone glucuronide was effective in curbing stearate
      induced lipoapoptosis. These results demonstrate that some flavanone metabolites,
      derived from the in vivo transformation of bergamot juice phenolics in humans,
      may mitigate stearate-induced inflammation in MACs.

PMID- 29211033
TI  - In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan
      Oat Cultivars.
AB  - Improvement of oat lines via introgression is an important process for food
      biochemical functionality. This work aims to evaluate the protective effect of
      phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on
      hyperglycemia-induced oxidative stress and to establish the possible mechanisms
      of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids
      were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic,
      salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract
      (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose
      (FBG) and oxidative stress markers, including Superoxide dismutase (SOD),
      Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and
      Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat
      intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic
      rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by
      their inhibitory activities on alpha-amylase (723.91 MUg/mL and 1027.14 MUg/mL)
      and alpha-glucosidase (1548.12 MUg/mL & 1803.52 MUg/mL) enzymes by mean of a
      mixed inhibition.

PMID- 29211034
TI  - Glucocorticoids Improve Myogenic Differentiation In Vitro by Suppressing the
      Synthesis of Versican, a Transitional Matrix Protein Overexpressed in Dystrophic
      Skeletal Muscles.
AB  - In Duchenne muscular dystrophy (DMD), a dysregulated extracellular matrix (ECM)
      directly exacerbates pathology. Glucocorticoids are beneficial therapeutics in
      DMD, and have pleiotropic effects on the composition and processing of ECM
      proteins in other biological contexts. The synthesis and remodelling of a
      transitional versican-rich matrix is necessary for myogenesis; whether
      glucocorticoids modulate this transitional matrix is not known. Here, versican
      expression and processing were examined in hindlimb and diaphragm muscles from
      mdx dystrophin-deficient mice and C57BL/10 wild type mice. V0/V1 versican (Vcan)
      mRNA transcripts and protein levels were upregulated in dystrophic compared to
      wild type muscles, especially in the more severely affected mdx diaphragm.
      Processed versican (versikine) was detected in wild type and dystrophic muscles,
      and immunoreactivity was highly associated with newly regenerated myofibres.
      Glucocorticoids enhanced C2C12 myoblast fusion by modulating the expression of
      genes regulating transitional matrix synthesis and processing. Specifically,
      Tgfbeta1, Vcan and hyaluronan synthase-2 (Has2) mRNA transcripts were decreased
      by 50% and Adamts1 mRNA transcripts were increased three-fold by glucocorticoid
      treatment. The addition of exogenous versican impaired myoblast fusion, whilst
      glucocorticoids alleviated this inhibition in fusion. In dystrophic mdx muscles,
      versican upregulation correlated with pathology. We propose that versican is a
      novel and relevant target gene in DMD, given its suppression by glucocorticoids
      and that in excess it impairs myoblast fusion, a process key for muscle
      regeneration.

PMID- 29211035
TI  - High-Resolution Structure Analysis of Antibody V5 and U4 Conformational Epitopes
      on Human Papillomavirus 16.
AB  - Cancers attributable to human papillomavirus (HPV) place a huge burden on the
      health of both men and women. The current commercial vaccines are genotype
      specific and provide little therapeutic benefit to patients with existing HPV
      infections. Identifying the conformational epitopes on the virus capsid supports
      the development of improved recombinant vaccines to maximize long-term protection
      against multiple types of HPV. Fragments of antibody (Fab) digested from the
      neutralizing monoclonal antibodies H16.V5 (V5) and H16.U4 (U4) were bound to
      HPV16 capsids and the structures of the two virus-Fab complexes were solved to
      near atomic resolution using cryo-electron microscopy. The structures reveal
      virus conformational changes, the Fab-binding mode to the capsid, the residues
      comprising the epitope and indicate a potential interaction of U4 with the minor
      structural protein, L2. Competition enzyme-linked immunosorbent assay (ELISA)
      showed V5 outcompetes U4 when added sequentially, demonstrating a steric
      interference even though the footprints do not overlap. Combined with our
      previously reported immunological and structural results, we propose that the
      virus may initiate host entry through an interaction between the icosahedral five
      fold vertex of the capsid and receptors on the host cell. The highly detailed
      epitopes identified for the two antibodies provide a framework for continuing
      biochemical, genetic and biophysical studies.

PMID- 29211036
TI  - Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast
      Differentiation by Downregulating the NF-kappaB Signaling Pathway.
AB  - Marine algae possess a variety of beneficial effects on human health. In this
      study, we investigated whether diphlorethohydroxycarmalol (DPHC), isolated from
      Ishige okamurae, a brown alga, suppresses receptor activator of nuclear factor
      kappaB ligand (RANKL)-induced osteoclast differentiation. DPHC significantly
      suppressed RANKL-induced osteoclast differentiation and macrophage-colony
      stimulating factor (M-CSF) expression in a dose-dependent manner. In addition, it
      significantly inhibited actin ring formation, the expression of osteoclast marker
      genes, such as tartrate-resistant acid phosphatase (TRAP), nuclear factor of
      activated T-cells cytoplasmic 1 (Nfatc1), cathepsin K (Ctsk), and dendritic cell
      specific transmembrane protein (Dcstamp), and osteoclast-induced bone resorption.
      Analysis of the RANKL-mediated signaling pathway showed that the phosphorylation
      of both IkappaB and p65 was specifically inhibited by DPHC. These results suggest
      that DPHC substantially suppresses osteoclastogenesis by downregulating the RANK
      NF-kappaB signaling pathway. Thus, it holds significant potential for the
      treatment of skeletal diseases associated with an enhanced osteoclast activity.

PMID- 29211037
TI  - In Silico Identification and In Vitro Evaluation of Natural Inhibitors of
      Leishmania major Pteridine Reductase I.
AB  - In a continuation of our computational efforts to find new natural inhibitors of
      a variety of target enzymes from parasites causing neglected tropical diseases
      (NTDs), we now report on 15 natural products (NPs) that we have identified as
      inhibitors of Leishmania major pteridine reductase I (LmPTR1) through a
      combination of in silico and in vitro investigations. Pteridine reductase (PTR1)
      is an enzyme of the trypanosomatid parasites' peculiar folate metabolism, and has
      previously been validated as a drug target. Initially, pharmacophore queries were
      created based on four 3D structures of LmPTR1 using co-crystallized known
      inhibitors as templates. Each of the pharmacophore queries was used to virtually
      screen a database of 1100 commercially available natural products. The resulting
      hits were submitted to molecular docking analyses in the substrate binding site
      of the respective protein structures used for the pharmacophore design. This
      approach led to the in silico identification of a total of 18 NPs with predicted
      binding affinity to LmPTR1. These compounds were subsequently tested in vitro for
      inhibitory activity towards recombinant LmPTR1 in a spectrophotometric inhibition
      assay. Fifteen out of the 18 tested compounds (hit rate = 83%) showed significant
      inhibitory activity against LmPTR1 when tested at a concentration of 50 uM. The
      IC50 values were determined for the six NPs that inhibited the target enzyme by
      more than 50% at 50 uM, with sophoraflavanone G being the most active compound
      tested (IC50 = 19.2 uM). The NPs identified and evaluated in the present study
      may represent promising lead structures for the further rational drug design of
      more potent inhibitors against LmPTR1.

PMID- 29211038
TI  - Prevalence of Self-Reported Diagnosed Cataract and Associated Risk Factors among
      Elderly South Africans.
AB  - This paper estimates the prevalence of self-reported cataract and associated risk
      factors among individuals aged >=50 years in South Africa. Data from a nationally
      representative cross-sectional Study on Global AGEing and Adult Health (SAGE) (N
      = 3646) conducted in South Africa from 2007-2008 was analyzed. The primary
      outcome was self-reported cataract, and exposures included socio-demographics,
      self-reported co-morbidities, and behavioral factors. Linearized multivariate
      logistic regression models were used. The weighted prevalence of self-reported
      diagnosed cataract was 4.4% (95%CI: 3.4-5.8). Prevalence was greater among
      individuals with advancing age (10.2%), higher quality of life (QoL) (5.9%),
      education (5.2%), and wealth (5.8%) than their counterparts. Prevalence was also
      higher among individuals with depression (17.5%), diabetes (13.3%), hypertension
      (9.1%), and stroke (8.4%) compared to those without these conditions, with the
      exception of obesity (4.2%). In the final multivariate model, the odds of self
      reported cataract were: 4.14 times higher among people >=70 years than 50 to 59
      year olds (95%CI: 2.28-7.50); 2.48 times higher in urban than rural residents
      (95%CI: 1.25-4.92); 5.16, 2.99, and 1.97 times higher for individuals with
      depression (95%CI: 1.92-13.86), hypertension (95%CI: 1.60-5.59), and diabetes
      (95%CI: 1.07-3.61), compared to those without these conditions.

PMID- 29211039
TI  - Association of Social Support and Medication Adherence in Chinese Patients with
      Type 2 Diabetes Mellitus.
AB  - The prevalence of diabetes is steadily increasing in China. When diabetes is
      uncontrolled, it generates dire consequences for health and well-being. Numerous
      studies have shown that health outcomes were associated with social support and
      medication adherence. Previous study confirmed that social support was associated
      with medication adherence in patients with heart failure, HIV diseases, and first
      episode psychosis. However, the relationship between social support and
      medication adherence in patients with type 2 diabetes mellitus (T2DM) is remains
      unclear. This study aims to examine whether social support is associated with
      medication adherence in patients with T2DM. This study was conducted in the First
      Affiliated Hospital of the General Hospital of the People's Liberation Army
      (PLA). In Beijing, a systematic random sample of 412 patients with T2DM over 18
      years was recruited at baseline, and demographic characteristics, clinical data
      and their assessment of social support were collected from medical records and
      self-reported questionnaires. 330 of these patients completed a self-report
      measure of medication adherence at the sixth month after baseline data
      collection. Regression analysis showed that social support presented a positive
      effect on medication adherence, additionally, support utilization and the
      subscale of social support exhibited a significantly strong influence on
      medication adherence in patients with T2DM. Although medication adherence was
      influenced by multiple factors, this finding confirmed that social support must
      be recognized as a core element in interventions aimed at improving in the
      management of patients with T2DM.

PMID- 29211040
TI  - Promoting Long-Term Health among People with Spinal Cord Injury: What's New?
AB  - A key ingredient to successful health promotion is a primary care provider who
      can offer an informed first response to lifestyle issues, emerging problems and
      chronic challenges. This article aims to assist family physicians to play their
      role in promoting the health of people with SCI, by summarizing the latest
      evidence in the management of spinal cord injury in primary care. This study used
      a scoping review methodology to survey peer-reviewed journal articles and
      clinical guidelines published between January 2012 to June 2016. This search
      strategy identified 153 articles across 20 topics. A prevention framework is used
      to identify five primary, nine secondary, four tertiary, and two quaternary
      prevention issues about which family physicians require current information.
      Major changes in the management of SCI in primary care were noted for 8 of the 20
      topics, specifically in the areas of pharmacological management of neuropathic
      pain and urinary tract infection; screening for bowel and bladder cancer;
      improvements in wound care; and clarification of dietary fibre recommendations.
      All of these changes are represented in the 3rd edition of Actionable Nuggets-an
      innovative tool to assist family physicians to be aware of the best practices in
      primary care for spinal cord injury.

PMID- 29211041
TI  - How to Obtain Forty Percent Less Environmental Impact by Healthy, Protein
      Optimized Snacks for Older Adults.
AB  - It is well known that meals containing less meat are more sustainable, but little
      is known about snack-meals, which typically do not contain meat. This study
      investigates the diversity in environmental impacts associated with snack
      production based on 20 common recipes optimized for protein content, energy
      content and sensory aspects for older adults. The purpose is to improve
      sustainability of public procurement by serving more sustainable snack-meals.
      Public procurement serves Danish older adults over millions of snack-meals every
      year, and millions more are served in countries with a similar social service.
      The environmental impact of snack production was estimated by consequential life
      cycle assessment. The average impact of producing the 10 least environmentally
      harmful snacks was 40% less than the average impact of producing the 10 most
      harmful snacks. This is true whether the functional unit was mass, energy, or
      protein content, and whether the environmental impact was measured as global
      warming potential or the monetized value of 16 impact categories. We conclude
      that large-scale public procurement of snack-meals by private and municipal
      kitchens can be reduced by up to 40% if the kitchens evaluate the environmental
      impact of all their snacks and serve the better half more frequently.

PMID- 29211042
TI  - Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy.
AB  - Cancer immunotherapy has been a great breakthrough, with immune checkpoint
      inhibitors leading the way. Despite the clinical effectiveness of certain immune
      checkpoint inhibitors, the overall response rate remains low, and the
      effectiveness of immunotherapies for many tumors has been disappointing. There is
      substantial interest in looking for additional immune checkpoint molecules that
      may act as therapeutic targets for cancer. Recent advances during the last decade
      have identified several novel immune checkpoint targets, including lymphocyte
      activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death
      1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based
      inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1
      (CEACAM1), and the poliovirus receptor (PVR)-like receptors. The investigations
      into these molecules have generated promising results in preclinical studies.
      Herein, we will summarize our current progress and understanding of these newly
      characterized immune checkpoints and their potential application in cancer
      immunotherapy.

PMID- 29211043
TI  - Detection of Water Content in Rapeseed Leaves Using Terahertz Spectroscopy.
AB  - The terahertz (THz) spectra of rapeseed leaves with different water content (WC)
      were investigated. The transmission and absorption spectra in the range of 0.3-2
      THz were measured by using THz time-domain spectroscopy. The mean transmittance
      and absorption coefficients were applied to analyze the change regulation of WC.
      In addition, the Savitzky-Golay method was performed to preprocess the spectra.
      Then, the partial least squares (PLS), kernel PLS (KPLS), and Boosting-PLS were
      conducted to establish models for predicting WC based on the processed
      transmission and absorption spectra. Reliable results were obtained by these
      three methods. KPLS generated the best prediction accuracy of WC. The prediction
      coefficient correlation (Rval) and root mean square error (RMSEP) of KPLS based
      on transmission were Rval = 0.8508, RMSEP = 0.1015, and that based on absorption
      were Rval = 0.8574, RMSEP = 0.1009. Results demonstrated that THz spectroscopy
      combined with modeling methods provided an efficient and feasible technique for
      detecting plant physiological information.

PMID- 29211045
TI  - Co-Cultured Continuously Bioluminescent Human Cells as Bioreporters for the
      Detection of Prodrug Therapeutic Impact Pre- and Post-Metabolism.
AB  - Modern drug discovery workflows require assay systems capable of replicating the
      complex interactions of multiple tissue types, but that can still function under
      high throughput conditions. In this work, we evaluate the use of substrate-free
      autobioluminescence in human cell lines to support the performance of these
      assays with reduced economical and logistical restrictions relative to substrate
      requiring bioluminescent reporter systems. The use of autobioluminescence was
      found to support assay functionality similar to existing luciferase reporter
      targets. The autobioluminescent assay format was observed to correlate strongly
      with general metabolic activity markers such as ATP content and the presence of
      reactive oxygen species, but not with secondary markers such as glutathione
      depletion. At the transcriptional level, autobioluminescent dynamics were most
      closely associated with expression of the CYP1A1 phase I detoxification pathway.
      These results suggest constitutively autobioluminescent cells can function as
      general metabolic activity bioreporters, while pairing expression of the
      autobioluminescent phenotype to detoxification pathway specific promoters could
      create more specific sensor systems.

PMID- 29211046
TI  - Building-Based Analysis of the Spatial Provision of Urban Parks in Shenzhen,
      China.
AB  - Urban parks provide important environmental, social, and economic benefits to
      people and urban areas. The literature demonstrates that proximity to urban parks
      is one of the key factors influencing people's willingness to use them.
      Therefore, the provision of urban parks near residential areas and workplaces is
      one of the key factors influencing quality of life. This study designed a
      solution based on the spatial association between urban parks and buildings where
      people live or work to identify whether people in different buildings have nearby
      urban parks available for their daily lives. A building density map based on
      building floor area (BFA) was used to illustrate the spatial distribution of
      urban parks and five indices were designed to measure the scales, service
      coverage and potential service loads of urban parks and reveal areas lacking
      urban park services in an acceptable walking distance. With such solution, we
      investigated the provision of urban parks in ten districts of Shenzhen in China,
      which has grown from several small villages to a megacity in only 30 years. The
      results indicate that the spatial provision of urban parks in Shenzhen is not
      sufficient since people in about 65% of the buildings cannot access urban parks
      by walking 10-min. The distribution and service coverage of the existing urban
      parks is not balanced at the district level. In some districts, the existing
      urban parks have good numbers of potential users and even have large service
      loads, while in some districts, the building densities surrounding the existing
      parks are quite low and at the same time there is no urban parks nearby some high
      density areas.

PMID- 29211044
TI  - Similarity and Differences in Inflammation-Related Characteristics of the
      Peripheral Immune System of Patients with Parkinson's and Alzheimer's Diseases.
AB  - Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common age
      related neurodegenerative disorders. Both diseases are characterized by chronic
      inflammation in the brain-neuroinflammation. The first signs of PD and AD are
      most often manifested in old age, in which the immune system is usually
      characterized by chronic inflammation, so-called "inflammaging" In recent years,
      there is growing evidence that pathogenesis of these diseases is connected with
      both regional and peripheral immune processes. Currently, the association of
      clinical signs of PD and AD with different characteristics of patient immune
      status is actively being researched. In this mini-review we compare the
      association of PD and AD alterations of a number of immune system parameters
      connected with the process of inflammation.

PMID- 29211047
TI  - A Chitosan-Based Liposome Formulation Enhances the In Vitro Wound Healing
      Efficacy of Substance P Neuropeptide.
AB  - Currently, there is considerable interest in developing innovative biodegradable
      nanoformulations for controlled administration of therapeutic proteins and
      peptides. Substance P (SP) is a neuropeptide of 11 amino acids that belongs to
      the tachykinins family and it plays an important role in wound healing. However,
      SP is easily degradable in vivo and has a very short half-life, so the use of
      chitosan-based nanocarriers could enhance its pharmaceutical properties. In light
      of the above, the aim of this work was to produce and characterize chitosan
      coated liposomes loaded with SP (SP-CH-LP) as novel biomaterials with potential
      application in mucosal wound healing. The loaded system's biophysical properties
      were characterized by dynamic light scattering with non-invasive back scattering
      (DLS-NIBS), mixed mode measurements and phase analysis light scattering (M3-PALS)
      and high performance liquid chromatography with ultraviolet/visible light
      detection (HPLC-UV/VIS). Then, the efficacy of the obtained nanoformulations was
      examined via proof-of-principle experiments using in vitro cell assays. These
      assays showed an increment on cell motility and proliferation after treatment
      with free and encapsulated neuropeptides. Additionally, the effect of SP on wound
      healing was enhanced by the entrapment on CH-LP. Overall, the amenability of
      chitosan-based nanomaterials to encapsulate peptides and proteins constitutes a
      promising approach towards potential novel therapies to treat difficult wounds.

PMID- 29211048
TI  - Imaging Characteristics of Malignant Sinonasal Tumors.
AB  - Malignancies of the nasal cavity and paranasal sinuses account for 1% of all
      malignancies and 3% of malignancies of the upper aerodigestive tract. In the
      sinonasal tract, nearly half of all malignancies arise in the nasal cavity,
      whereas most of the remaining malignancies arise in the maxillary or ethmoid
      sinus. Squamous cell carcinoma is the most common histological subtype of
      malignant tumors occurring in this area, followed by other epithelial carcinomas,
      lymphomas, and malignant soft tissue tumors. Although many of these tumors
      present with nonspecific symptoms, each tumor exhibits characteristic imaging
      features. Although complex anatomy and various normal variants of the sinonasal
      tract cause difficulty in identifying the origin and extension of large sinonasal
      tumors, the invasion of vital structures such as the brain, optic nerves, and
      internal carotid artery affects patients' prognosis. Thus, diagnostic imaging
      plays a key role in predicting the histological subtype and in evaluating a tumor
      extension into adjacent structures. This article describes the computed
      tomography and magnetic resonance imaging findings for malignant sinonasal
      tumors.

PMID- 29211050
TI  - Luminescence-Based Optical Sensors Fabricated by Means of the Layer-by-Layer Nano
      Assembly Technique.
AB  - Luminescence-based sensing applications range from agriculture to biology,
      including medicine and environmental care, which indicates the importance of this
      technique as a detection tool. Luminescent optical sensors are required to be
      highly stable, sensitive, and selective, three crucial features that can be
      achieved by fabricating them by means of the layer-by-layer nano-assembly
      technique. This method permits us to tailor the sensors' properties at the
      nanometer scale, avoiding luminophore aggregation and, hence, self-quenching,
      promoting the diffusion of the target analytes, and building a barrier against
      the undesired molecules. These characteristics give rise to the fabrication of
      custom-made sensors for each particular application.

PMID- 29211051
TI  - Microwave Non-Destructive Inspection and Prediction of Modulus of Rupture and
      Modulus of Elasticity of Engineered Cementitious Composites (ECCs) Using Dual
      Frequency Correlation.
AB  - This research article presents dual-frequency correlation models for predicting
      the growth of elasticity and flexural strength of engineered cementitious
      composites (ECCs) using microwave nondestructive inspection technique. Parallel
      measurements of microwave properties and mechanical properties of ECC specimens
      were firstly undertaken in the sense of cross-disciplinary experiments.
      Regression models were developed via means of nonlinear regression to the
      measured data. The purpose of the study is: (i) to monitor the flexural strength
      and elasticity growth; and (ii) to predict their mature values under the
      influence of different initial water contents, via microwave effective
      conductance at early ages. It has been demonstrated that both the modulus of
      rupture (MOR) and modulus of elasticity (MOE) can be accurately modeled and
      correlated by microwave conductance using exponential functions. The moduli
      developed as a function of conductance whereas the regression coefficient
      exhibited a linear relation with water-to-binder ratio. These findings have
      highlighted the effectiveness of the microwave non-destructive technique in
      inspecting the variation of liquid phase morphology of ECCs. The dual-frequency
      correlation can be used for structural health monitoring, which is not only for
      prediction but also provides a means of verification.

PMID- 29211052
TI  - Maternal Vaccination. Immunization of Sows during Pregnancy against ETEC
      Infections.
AB  - The immunology of pregnancy is an evolving consequence of multiple reciprocal
      interactions between the maternal and the fetal-placental systems. The immune
      response must warrant the pregnancy outcome (including tolerance to paternal
      antigens), but at the same time, efficiently respond to pathogenic challenges.
      Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and
      death in neonatal and recently weaned pigs. This review aims to give an overview
      of the current rationale on the maternal vaccination strategies for the
      protection of the newborn pig against ETEC. Newborn piglets are immunodeficient
      and naturally dependent on the maternal immunity transferred by colostrum for
      protection-a maternal immunity that can be obtained by vaccinating the sow during
      pregnancy. Our current knowledge of the interactions between the pathogen
      strategies, virulence factors, and the host immune system is aiding the better
      design of vaccination strategies in this particular and challenging host status.
      Challenges include the need for better induction of immunity at the mucosal level
      with the appropriate use of adjuvants, able to induce the most appropriate and
      long-lasting protective immune response. These include nanoparticle-based
      adjuvants for oral immunization. Experiences can be extrapolated to other
      species, including humans.

PMID- 29211054
TI  - Barriers and Facilitators for Information Exchange during Over-The-Counter
      Consultations in Community Pharmacy: A Focus Group Study.
AB  - Consumers are confident managing minor ailments through self-care, often self
      medicating from a range of over-the-counter (OTC) medicines available from
      community pharmacies. To minimise risks, pharmacy personnel endeavour to engage
      in a consultation when consumers present with OTC enquiries however they find
      consumers resistant. The aim was to determine stakeholder perspectives regarding
      barriers and facilitators for information exchange during OTC consultations in
      community pharmacies and to understand the elicited themes in behavioural terms.
      Focus groups were undertaken with community pharmacist, pharmacy assistant and
      consumer participants. Independent duplicate analysis of transcription data was
      conducted using inductive and framework methods. Eight focus groups involving 60
      participants were conducted. Themes that emerged indicated consumers did not
      understand pharmacists' professional role, they were less likely to exchange
      information if asking for a specific product than if asking about symptom
      treatment, and they wanted privacy. Consumers were confident to self-diagnose and
      did not understand OTC medicine risks. Pharmacy personnel felt a duty of care to
      ensure consumer safety, and that with experience communication skills developed
      to better engage consumers in consultations. They also identified the need for
      privacy. Consumers need education about community pharmacists' role and
      responsibilities to motivate them to engage in OTC consultations. They also
      require privacy when doing so.

PMID- 29211053
TI  - Impacts of Small-Scale Industrialized Swine Farming on Local Soil, Water and Crop
      Qualities in a Hilly Red Soil Region of Subtropical China.
AB  - Industrialized small-scale pig farming has been rapidly developed in developing
      regions such as China and Southeast Asia, but the environmental problems
      accompanying pig farming have not been fully recognized. This study investigated
      168 small-scale pig farms and 29 example pig farms in Yujiang County of China to
      examine current and potential impacts of pig wastes on soil, water and crop
      qualities in the hilly red soil region, China. The results indicated that the
      small-scale pig farms produced considerable annual yields of wastes, with medians
      of 216, 333 and 773 ton yr-1 per pig farm for manure, urine and washing
      wastewater, respectively, which has had significant impact on surface water
      quality. Taking NH4+-N, total nitrogen (TN) or total phosphorus (TP) as a
      criterion to judge water quality, the proportions of Class III and below Class
      III waters in the local surface waters were 66.2%, 78.7% and 72.5%. The well
      water (shallow groundwater) quality near these pig farms met the water quality
      standards by a wide margin. The annual output of pollutants from pig farms was
      the most important factor correlated with the nutrients and heavy metals in
      soils, and the relationship can be described by a linear equation. The impact on
      croplands was marked by the excessive accumulation of available phosphorus and
      heavy metals such as Cu and Zn. For crop safety, the over-limit ratio of Zn in
      vegetable samples reached 60%, other heavy metals in vegetable and rice samples
      tested met the food safety standard at present.

PMID- 29211055
TI  - Urinary C-megalin for screening of renal scarring in children after febrile
      urinary tract infection.
AB  - BackgroundFebrile urinary tract infection (fUTI) in children may cause renal
      scarring. This study aimed to investigate the usefulness of urinary biomarkers
      for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median
      age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who
      underwent renal scintigraphy for 4 months or longer after the last episode of
      fUTI, were analyzed. A spot urine sample was obtained on the day of renal
      scintigraphy to measure levels of total protein, N-acetyl-beta-D-glucosaminidase
      (NAG), beta2-microglobulin (BMG), neutrophil gelatinase-associated lipocalin
      (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full
      length megalin). Results were corrected for urinary creatinine (Cr) and compared
      between the group with renal scarring (n=23) and that without scarring (n=14).
      Urinary levels of C-megalin were also measured in healthy control
      subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG,
      and BMG levels were found between the groups. However, C-megalin levels were
      significantly higher in the renal scarring group than in the non-renal scarring
      group and healthy controls (P<0.001). A cutoff value of 6.5 pmol/nmol of urinary
      C-megalin/Cr yielded 73.9% of specificity and 92.9% of
      sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring
      caused by fUTI.

PMID- 29211056
TI  - Krebs cycle metabolites and preferential succinate oxidation following neonatal
      hypoxic-ischemic brain injury in mice.
AB  - BackgroundReverse electron transport (RET) driven by the oxidation of succinate
      has been proposed as the mechanism of accelerated production of reactive oxygen
      species (ROS) in post-ischemic mitochondria. However, it remains unclear whether
      upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal
      mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI)
      followed by assessment of Krebs cycle metabolites, mitochondrial substrate
      preference, and H2O2 generation rate in the ischemic brain.ResultsWhile brain
      mitochondria from control mice exhibited a rotenone-sensitive complex-I-dependent
      respiration, HI-brain mitochondria, at the initiation of reperfusion,
      demonstrated complex-II-dependent respiration, as rotenone minimally affected,
      but inhibition of complex-II ceased respiration. This was associated with a 30
      fold increase of cerebral succinate concentration and significantly elevated H2O2
      emission rate in HI-mice compared to controls. At 60 min of reperfusion, cerebral
      succinate content and the mitochondrial response to rotenone did not differ from
      that in controls.ConclusionThese data are the first ex vivo evidence, that at the
      initiation of reperfusion, brain mitochondria transiently shift their metabolism
      from complex-I-dependent oxidation of NADH toward complex II-linked oxidation of
      succinate. Our study provides a critical piece of support for existence of the
      RET-dependent mechanism of elevated ROS production in reperfusion.

PMID- 29211057
TI  - Neonatal neutrophils stimulated by group B Streptococcus induce a proinflammatory
      T-helper cell bias.
AB  - BackgroundGroup B Streptococcus (GBS) infection causes inflammatory comorbidities
      in newborns. While the mechanisms remain unclear, evidence suggests that impaired
      innate-adaptive immune interactions may be contributory. We hypothesized that GBS
      stimulated neonatal neutrophils provide a milieu that may drive proinflammatory T
      helper (Th) cell programming.MethodsNeutrophils were stimulated with Type III GBS
      (COH1); supernatants or intact neutrophils were cocultured with CD4+ T cells or
      regulatory T cells (Tregs). Resulting intracellular cytokines and nuclear
      transcription factors were determined by multicolor flow cytometry.ResultsGBS
      stimulated neutrophils released soluble mediators that induced greater
      interleukin-17 (IL-17) responses in neonatal vs. adult CD4+ T cells in the
      absence of added polarizing cytokines. GBS-stimulated neonatal neutrophils also
      induced robust expression of the canonical nuclear transcription factors for Th1
      (Tbet) and Th17 (IL-17) cells in CD4+ T cells. Following GBS stimulation, both
      intact neutrophils and neutrophil-derived mediators promoted the generation of
      Tregs with Th1 and Th17 characteristics.ConclusionGBS-stimulated neonatal
      neutrophils bias the in vitro Th differentiation program of neonatal CD4+ T cells
      and promote proinflammatory Th1 and Th17 phenotypes in Tregs. Our data suggest
      that developmental modifications of innate-adaptive immune cross-talk mechanisms
      may contribute to the inflammatory complications associated with neonatal GBS
      infection.

PMID- 29211058
TI  - Decreased lymphocytes and increased risk for infection are common in endogenous
      pediatric Cushing syndrome.
AB  - BackgroundHypercortisolemia results in changes of the immune system and elevated
      infection risk, but data on the WBC changes in pediatric Cushing syndrome (CS)
      are not known. We describe the changes of the WBC lineages in pediatric
      endogenous hypercortisolemia, their associations with the markers of disease
      severity, and the presence of infections.MethodsWe identified 197 children with
      endogenous CS. Clinical and biochemical data were recorded. Sixty-six children
      with similar age and gender, and normocortisolemia served as controls.ResultsThe
      absolute lymphocyte count of CS patients was significantly lower than that of
      controls, while the total WBC and the absolute neutrophil counts were
      significantly higher. These changes correlated with several markers of CS
      severity and improved after resolution of hypercortisolemia. Infections were
      identified in 35 patients (17.8%), and their presence correlated to elevated
      serum morning cortisol, midnight cortisol, and urinary free cortisol levels, as
      well as with the decrease in absolute lymphocyte count.ConclusionsChildren with
      endogenous CS have abnormal WBC counts, which correlate with the severity of CS,
      and normalize after cure. Infections are common in this population; clinicians
      should be aware of this complication of CS and have low threshold in diagnosis
      and treating infections in CS.

PMID- 29211059
TI  - Improving clinical diagnosis in SHOX deficiency: the importance of growth
      velocity.
AB  - BackgroundThe aim of this study was to estimate the prevalence of
      haploinsufficiency of short stature homeobox containing gene (SHOX) deficiency
      (SHOXD) in a population of short-statured children, and to analyze their
      phenotype and the performance of clinical scores.MethodsScreening for SHOXD was
      performed in 281 children with short stature by direct sequencing and multiplex
      ligation probe-dependent amplification. Subjects with SHOXD were compared with
      117 matched short patients without SHOXD. We calculated the cutoff of growth
      velocity associated with the highest sensitivity and specificity as a screening
      test for SHOXD by receiver operating characteristic curves.ResultsThe prevalence
      of SHOXD was 6.8%. Subjects with SHOXD showed a lower growth velocity (P<0.05)
      and a higher prevalence of dysmorphic signs. The best cutoff for growth velocity
      was -1.5 standard deviation score (SDS) both in the whole population and in
      subjects with a Rappold score <7 and <4 points. Growth velocity was <=-1.5 SDS or
      Rappold score was >7/>4 points in 17/17 of 19 children with SHOXD and in 49/65 of
      117 subjects without SHOX mutations.ConclusionsGrowth rate <=-1.5 SDS, even with
      negative Rappold score, may be useful to detect precociously children with SHOXD.
      Selecting children deserving the genetic test by using growth velocity or the
      Rappold score significantly increases the sensitivity in detecting mutations and
      decreases the specificity.

PMID- 29211060
TI  - Hurricane Harvey and climate change: the need for policy to protect children.

PMID- 29211061
TI  - Erratum to "Prediction of Treatment Response to Donepezil using Automated
      Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's
      Disease".
AB  - [This corrects the article on p. 698 in vol. 14.].

PMID- 29211062
TI  - Corrigendum to "Microscopic Examination of Cold Spray Cermet Sn+In2O3 Coatings
      for Sputtering Target Materials".
AB  - [This corrects the article DOI: 10.1155/2017/4058636.].

PMID- 29211063
TI  - Corrigendum: Serum Metabolic Alterations upon Zika Infection.
AB  - [This corrects the article on p. 1954 in vol. 8, PMID: 29067015.].

PMID- 29211064
TI  - Controlling the lectin recognition of glycopolymers via distance arrangement of
      sugar blocks.
AB  - The arrangement of sugars in glycopolymers contributes to their recognition. The
      molecular recognition of proteins was controlled by the living radical
      polymerization of glycopolymers. The glycopolymers were prepared by the
      copolymerization of propargyl methacrylate (Pr-MA) and triethyleneglycol
      methacrylate (TEG-MA) via living radical polymerization with a reversible
      addition-fragmentation glycopolymer chain transfer (RAFT) reagent and by
      subsequent sugar conjugation by click chemistry. The block copolymers were
      prepared by the polymerization of Pr-MA and TEG-MA. The molecular recognition of
      glycopolymers was analyzed using the fluorescence quenching of lectin and found
      to be dependent on the glycopolymer structures. Two-site binding of glycopolymers
      to concanavalin A (ConA) was attained by both the glycopolymer with a 105-mer and
      the tri-block glycopolymer with a 103-mer. Glycopolymers with either a 27- or 54
      mer showed much weaker interaction because of one-site binding. The molecular
      recognition of the glycopolymer was controlled by the arrangement and size of the
      sugar cluster and not by the sugar density.

PMID- 29211065
TI  - Bright NUV mechanofluorescence from a terpyridine-based pure organic crystal.
AB  - A bright NUV mechanofluorescent terpyridine-based material with a piezoelectric
      space group was obtained. The single crystal analysis and quantum chemical
      calculations indicated the existence of enhanced intermolecular and
      intramolecular interactions and intersystem crossing, but which did not
      facilitate the room temperature phosphorescence.

PMID- 29211066
TI  - Cobalt-catalyzed acceptorless dehydrogenative coupling of aminoalcohols with
      alcohols: direct access to pyrrole, pyridine and pyrazine derivatives.
AB  - Here, the first example is reported of a new, molecularly defined SNS-cobalt(ii)
      catalyst for the acceptorless dehydrogenative coupling (ADC) of unprotected amino
      alcohols with secondary alcohols leading to pyrrole and pyridine derivatives.

PMID- 29211049
TI  - Living Organisms Author Their Read-Write Genomes in Evolution.
AB  - Evolutionary variations generating phenotypic adaptations and novel taxa resulted
      from complex cellular activities altering genome content and expression: (i)
      Symbiogenetic cell mergers producing the mitochondrion-bearing ancestor of
      eukaryotes and chloroplast-bearing ancestors of photosynthetic eukaryotes; (ii)
      interspecific hybridizations and genome doublings generating new species and
      adaptive radiations of higher plants and animals; and, (iii) interspecific
      horizontal DNA transfer encoding virtually all of the cellular functions between
      organisms and their viruses in all domains of life. Consequently, assuming that
      evolutionary processes occur in isolated genomes of individual species has become
      an unrealistic abstraction. Adaptive variations also involved natural genetic
      engineering of mobile DNA elements to rewire regulatory networks. In the most
      highly evolved organisms, biological complexity scales with "non-coding" DNA
      content more closely than with protein-coding capacity. Coincidentally, we have
      learned how so-called "non-coding" RNAs that are rich in repetitive mobile DNA
      sequences are key regulators of complex phenotypes. Both biotic and abiotic
      ecological challenges serve as triggers for episodes of elevated genome change.
      The intersections of cell activities, biosphere interactions, horizontal DNA
      transfers, and non-random Read-Write genome modifications by natural genetic
      engineering provide a rich molecular and biological foundation for understanding
      how ecological disruptions can stimulate productive, often abrupt, evolutionary
      transformations.

PMID- 29211067
TI  - Branched peptides for enzymatic supramolecular hydrogelation.
AB  - Here we show the use of branched peptides (i.e., isopeptides) as the substrates
      of proteases for generating supramolecular hydrogels via enzymatically clipping
      the branch off the peptides. As the first report of using a protease to cut
      branched peptides to enable a molecular process for converting nanostructures,
      this work illustrates a fundamentally new molecular motif for exploring the
      applications of protease-instructed self-assembly for soft materials.

PMID- 29211068
TI  - Spontaneous protein desorption from self-assembled monolayer (SAM)-coated gold
      nanoparticles.
AB  - When nanoparticles enter blood or other biological fluids, they tend to contact
      with a variety of proteins which may hamper their application and even bring
      adverse impacts. Such nonspecific protein binding is usually weak and proteins
      reach dynamic equilibrium between adsorption and desorption. Studies on the
      spontaneous desorption of weakly bound proteins should not only be helpful to
      enrich our understanding about such nonspecific interactions but also shed light
      on the strategy to avoid nonspecific binding of proteins. Here, we use molecular
      dynamics simulations to investigate the interactions of human serum albumin with
      the self-assembled monolayer (SAM)-coated gold(111) surface, a typical facet of
      various gold nanoparticles. The response of the protein interfacial behavior to
      solution pH, especially the spontaneous desorption, is studied. When the solution
      pH is relatively low, the protein can adsorb to the SAM surface. Such adhesion is
      attributed to several salt bridges between acidic residues and SAM's protonated
      groups, and there are water molecules distributed under the adsorbed protein,
      i.e. interlayer water. Interestingly, the increase of the solution pH reduces the
      binding affinity of the protein, which engenders the lateral diffusion of the
      protein and the increase of interlayer water. When the solution pH is further
      increased, the enhanced lateral diffusion of the protein and the growth of
      interlayer water disrupt the formation of salt bridges between the protein and
      the SAM, and the protein progressively dissociates from the SAM. The spontaneous
      desorption process of the protein and the corresponding mechanisms illustrated in
      this work may be helpful to develop an antifouling surface and enhance the
      biosafety of nanomaterials.

PMID- 29211069
TI  - Development of a framework catalyst for photocatalytic hydrogen evolution.
AB  - The controlled self-assembly of a catalyst module composed of a Rh(ii) paddle
      wheel dimer bearing 1,8-naphthalimide-based moieties afforded a novel
      heterogeneous framework catalyst (FC-1). The framework catalyst exhibited long
      lived activity for photocatalytic hydrogen production from water and was easily
      reused without considerable loss of catalytic activity.

PMID- 29211070
TI  - 2-(1-Methylhydrazinyl)pyridine as a reductively removable directing group in a
      cobalt-catalyzed C(sp2)-H bond alkenylation/annulation cascade.
AB  - We describe a new application of 2-(1-methylhydrazinyl)pyridine as a bidentate
      directing group to directing cobalt-catalyzed C(sp2)-H alkenylation/annulation of
      the corresponding benzoic hydrazides to form an isoquinoline backbone, via
      reacting with a terminal or internal alkyne followed by annulation. The reaction
      shows a broad substrate scope with the products obtained in good to excellent
      yields and high regioselectivity. Moreover, the directing group can be
      reductively removed in one step under mild conditions.

PMID- 29211071
TI  - Molecular dynamics simulation of geminal dicationic ionic liquids
      [Cn(mim)2][NTf2]2 - structural and dynamical properties.
AB  - In this work, the structural and dynamical properties of two imidazolium-based
      geminal dicationic ionic liquids (GDILs), i.e. [Cn(mim)2][NTf2]2 with n = 3 and
      5, have been studied to obtain a fundamental understanding of the molecular basis
      of the macroscopic and microscopic properties of the bulk liquid phase. To
      achieve this purpose, molecular dynamics (MD) simulation, density functional
      theory (DFT) and atoms in molecule (AIM) methods were used. Interaction energies,
      charge transfers and hydrogen bonds between the cation and anions of each studied
      GDIL were investigated by DFT calculations and also AIM. The mean square
      displacement (MSD), self-diffusion coefficient, and transference number of the
      cation and anions, and also the density, viscosity and electrical conductivity of
      the studied GDILs, were computed at 333.15 K and at 1 atm. The simulated values
      were in good agreement with the experimental data. The effect of linkage alkyl
      chain length on the thermodynamic, transport and structural properties of these
      GDILs has been investigated. The structural features of these GDILs were
      characterized by calculating the partial site-site radial distribution functions
      (RDFs) and spatial distribution functions (SDFs). The heterogeneity order
      parameter (HOP) has been used to describe the spatial structures of these GDILs
      and the distribution of the angles formed between two cation heads and the middle
      carbon atom of the linkage alkyl chain was analyzed in these ILs. To investigate
      the temporal heterogeneity of the studied GDILs, the deviation of the self-part
      of the van Hove correlation function, Gs(r[combining right harpoon above],t),
      from the Gaussian distribution of particle displacement and also the second-order
      non-Gaussian parameter, alpha2(t), were used. Since, the transport and
      interfacial properties and ionic characteristics of these GDILs were studied
      experimentally in our previous studies as a function of linkage chain length and
      temperature, in this work, we try to give a better perspective of the structure
      and dynamics of these systems at a molecular level.

PMID- 29211072
TI  - Influences of polarity and hydration cycles on imbibition hysteresis in silica
      nanochannels.
AB  - Spontaneous liquid imbibition is a dominant mechanism for moving fluids in
      confinements with extremely high hydrodynamic resistance; i.e. nanopores. We
      demonstrate the impact of hydrophilicity and liquid polarity on nanoscale
      imbibition with dynamic measurements of the uptake of water-isopropanol (polar)
      and heptane (nonpolar) within 2D glass-silica nanochannels exposed to varied
      drying conditions and rehydration (rehydroxylation) cycles. The Lucas-Washburn
      equation, which does not consider interfacial fluidity effects, predicts that
      water-IPA and heptane should imbibe at similar speeds. However, we observed
      stymied and hysteretic water-IPA imbibition trends explained by extremely large
      contact line friction and increased effective viscosity, both surface chemistry
      dependent, whereupon the results match a modified version of the Lucas-Washburn
      equation that accounts for dynamic wetting. In contrast, heptane imbibition,
      though still slower than the Lucas-Washburn equation prediction, was fairly
      insensitive to drying history and an order of magnitude faster than the polar
      mixture. The imbibition of aqueous solutions in analogous siliceous nanoporous
      materials and structures, ubiquitous in earth science and nanotechnology, may
      also be subject to hysteretic and large energy dissipation at contact lines and
      interfaces on account of hydrophilicity.

PMID- 29211073
TI  - Design of a wearable and shape-memory fibriform sensor for the detection of
      multimodal deformation.
AB  - A wearable and shape-memory strain sensor with a coaxial configuration is
      designed, comprising a thermoplastic polyurethane fiber as the core support, well
      aligned and interconnected carbon nanotubes (CNTs) as conductive filaments, and
      polypyrrole (PPy) coating as the cladding layer. In this design, the stress
      relaxation between CNTs is well confined by the outer PPy cladding layer, which
      endows the fibriform sensor with good reliability and repeatability. The
      microcracks generated when the coaxial fiber is under strain guarantee the
      superior sensitivity of this fibriform sensor with a gauge factor of 12 at 0.1%
      strain, a wide detectable range (from 0.1% to 50% tensile strain), and the
      ability to detect multimodal deformation (tension, bending, and torsion) and
      human motions (finger bending, breathing, and phonation). In addition, due to its
      shape-memory characteristic, the sensing performance of the fibriform sensor is
      well retained after its shape recovers from 50% deformation and the fabric woven
      from the shape-memory coaxial fibers can be worn on the elbow joints in a
      reversible manner (original-enlarged-recovered) and fitted tightly. Thus, this
      sensor shows promising applications in wearable electronics.

PMID- 29211076
TI  - CO ligands stabilize metal chalcogenide Co6Se8(CO)n clusters via demagnetization.
AB  - The role of carbon monoxide ligands on the magnetic moment of Co6Se8(CO)n
      clusters, n = 0-6 was investigated to better understand the interplay between the
      electronic structure of metal chalcogenide clusters and their ligands. We find
      that the addition of CO ligands to Co6Se8 results in the gradual demagnetization
      of the cluster. Generally, the addition of a CO ligand effectively adds two
      electrons to the cluster that occupy deeper states and further pushes up an
      antibonding orbital out of the valence manifold of cluster states. Through such
      processes, the fully ligated Co6Se8(CO)6 cluster attains a closed electronic
      shell with a large gap between occupied and unoccupied states. Each removal of a
      CO ligand from the cluster then stabilizes an antibonding state that adds
      unoccupied states to the valence manifold. Such a cluster with partially filled
      states may either deform as in a Jahn-Teller distortion to quench the spin, or
      maintain its core structure and be stabilized in a high spin state as in Hund's
      rules. As these clusters generally maintain their octahedral core, the high spin
      state prevails and the removal of the ligands results in an increase in spin
      multiplicity.

PMID- 29211077
TI  - Self-cleaning by harnessing wrinkles in two-dimensional layered crystals.
AB  - Two-dimensional (2D) layered crystals are prone to bending and folding owing to
      their ultra-low bending stiffness. Folds are traditionally viewed as defects that
      degrade the material performance. Here, we demonstrate that folds and cohesive
      forces in 2D layered crystals like graphene and MoS2 can be exploited to collect
      and clean up interlayer impurities, wherein multiple separated impurities
      agglomerate into a single, large cluster. We combine classical molecular dynamics
      simulations and an analytical model to elucidate the competing roles of membrane
      bending and impurity-membrane cohesive energies in the self-cleaning process. Our
      findings shed light on the mechanisms by which the forces that are present in 2D
      layered crystals can positively impact, through the possibility of intrinsic
      cleaning and defect engineering, the synthesis of van der Waals homo- and
      heterostructures with improved reliability and functionalities.

PMID- 29211078
TI  - A hydrolytically stable uranyl organic framework for highly sensitive and
      selective detection of Fe3+ in aqueous media.
AB  - We present a depleted uranium-based metal organic framework, UO2(C8H3O6N).DMF,
      that exhibits highly sensitive and selective detection towards Fe3+ ions in
      aqueous media with an extremely low detection limit of 6.3 ppb. This work offers
      insight into exploring the potential applications of actinide-based metal organic
      frameworks in the area of chemical sensing with intrinsic advantages of high
      selectivity and sensitivity.

PMID- 29211080
TI  - Can electrostatic catalysis of Diels-Alder reactions be harnessed with pH
      switchable charged functional groups?
AB  - Quantum-chemical calculations at the M06-2X/6-31+G(d,p) and G3(MP2)CC levels of
      theory are used to assess the feasibility of harnessing charged functional groups
      to electrostatically catalyse Diels-Alder reactions and alter their regio
      selectivity. For the reaction of the polar diene 2-pyrone with substituted
      cyclopentene, pH switches of nearly 60 kJ mol-1 are observed in the gas-phase. To
      switch regioselectivity however it is necessary to toggle between negatively and
      positively charged functional groups. With the 6-membered cyclohexene
      derivatives, similar pH-switches are observed but this time an opportunity to pH
      switch diastereomeric selectivity is also observed due to the asymmetry of the
      transition state. When 2-pyrone was replaced with a non-polar diene,
      cyclopentadiene, pH switches were understandably smaller but still substantial
      (ca. 15 kJ mol-1). Likewise pH switches are attenuated by solvent but remain
      substantial (ca. 30 kJ mol-1) in toluene and synthetically useful (ca. 15 kJ mol
      1) even in moderately low polar solvents such as dichloromethane.

PMID- 29211079
TI  - Probing the conformational dynamics of photosystem I in unconfined and confined
      spaces.
AB  - The fluorescence dynamics of Photosystem I (PSI) in bulk water and inside a
      confined environment like a liposome have been investigated using time resolved
      confocal microscopy. In bulk water, PSI exhibits a major emission peak at ~680
      nm, while in the liposome it exhibits a markedly blue shifted emission maximum at
      ~485 nm. This is indicative of conformational changes due to entrapment and
      emergence of a stressed conformation of PSI inside the liposome. The observed
      time constants for the fluorescence lifetime of PSI inside the liposome are
      significantly high as opposed to PSI in bulk water. More interestingly, the
      fluorescence intensity of PSI in bulk water exhibits strong fluctuations with
      many high intensity jumps and these are anti-correlated with the fluorescence
      lifetime of PSI. In contrast, inside the liposome, no such anti-correlated
      behaviour is observed. We further demonstrated that PSI exhibits at least two
      conformational states in bulk water, whereas a single conformation is observed
      inside the liposome, indicating the conformational rigidity and locking of the
      PSI complex inside a liposome.

PMID- 29211082
TI  - Indirect evidence for a NiIII-oxyl oxidant in the reaction of a NiII complex with
      peracid.
AB  - The reaction of a NiII complex and meta-chloroperoxybenzoic acid (m-CPBA)
      resulted in the formation of a long-lived NiIII-chlorobenzoate complex that is a
      capable hydrocarbon oxidant. Analysis of the post-reaction decay products showed
      the formation of oxidised derivatives of the supporting ligand (a benzoxazine),
      and heterolytic O-O bond scission in m-CPBA. This evidence indicates formation of
      a more potent transient NiIII-oxyl species, which was further supported by DFT
      calculations.

PMID- 29211084
TI  - Efficient two-photon luminescence for cellular imaging using biocompatible
      nitrogen-doped graphene quantum dots conjugated with polymers.
AB  - Nitrogen-doped graphene quantum dot (N-GQD) nanomaterials conjugated with
      polyethylenimine (PEI)-polystyrene sulfonate (PSS)-anti-epidermal growth factor
      receptor (AbEGFR) antibody (N-GQD-PEI-PSS-AbEGFR) demonstrated impressive two
      photon properties and stability, signifying that they can serve as an effective
      two-photon contrast agent in two-photon bioimaging. Furthermore, they provided
      high intensity, brightness, and signal-to-noise ratios at an ultra-low two-photon
      excitation (TPE) power level in an observation extending to a deep, three
      dimensional depth.

PMID- 29211085
TI  - Cancer immunotherapy MU-environment LabChip: taking advantage of optoelectronic
      tweezers.
AB  - A cancer immunotherapy MU-environment LabChip, equipped with titanium oxide
      phthalocyanine (TiOPc)-based optoelectronic tweezers (OET) to achieve direct cell
      cell contact, can be used to study the interaction between immune cells and other
      cells for real-time analysis of NK cells' behavior. In microfluidic devices, it
      is difficult to solve dead zone problems and observe dynamic cell-cell
      interactions. We have created a stable and static culture MU-environment which
      can enhance NK cell activities. In addition, OET is used to solve dead zone
      problems by manipulating a single cell into four-leaf-clover-shaped (FLCS)
      microwells made of poly(ethylene glycol) diacrylate (PEG-DA) through optofluidic
      maskless lithography, causing direct cell-cell contact. Our design reconstructed
      an in vitro human immune system for the study of dynamic immunological response.
      When the NK cells came into contact with the target cells in the MU-environment
      LabChip, we observed that the target cells showed apoptotic characteristics (i.e.
      cell shrinkage and blebbing within 2 h and then die within 3 h). In addition, our
      MU-environment LabChip demonstrated higher NK cell activity compared with
      conventional analysis. We have created an innovative cancer immunotherapy MU
      environment LabChip to provide a stable and static MU-environment for cell-cell
      interaction study. Furthermore, our MU-environment LabChip showed the potential
      to enhance NK cell activity and to study immunological interactions between
      immune cells and cancer cells dynamically.

PMID- 29211087
TI  - Correction: Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion
      of cod liver oil: comparison of human and porcine in vitro digestion models.
AB  - Correction for 'Formation of reactive aldehydes (MDA, HHE, HNE) during the
      digestion of cod liver oil: comparison of human and porcine in vitro digestion
      models' by Cecilia Tullberg et al., Food Funct., 2016, 7, 1401-1412.

PMID- 29211088
TI  - Multi-size spheroid formation using microfluidic funnels.
AB  - We present a microfluidic platform for automatic multi-size spheroid formation
      within constant volume hanging droplets (HDs) from a single inlet loading of a
      constant cell concentration. The platform introduces three technological
      improvements over the existing spheroid formation platforms: 1) cell seeding
      control is achieved by enrichment of a cell solution rather than dilution; 2)
      cell seeding in each HD is fully independent and pre-programmable at the design
      stage; 3) the fabricated chip operates well using a hydrophobic PDMS surface,
      ensuring long-term storage possibility for device usage. Pre-programmed cell
      seeding densities at each HD are achieved using a "microfluidic funnel" layer,
      which has an array of cone-shaped wells with increasing apex angles acting as a
      metering unit. The integrated platform is designed to form, treat, stain, and
      image multi-size spheroids on-chip. Spheroids can be analyzed on-chip or easily
      transferred to conventional well plates for further processing. Empirically,
      enrichment factors up to 37* have been demonstrated, resulting in viable
      spheroids of diameters ranging from 230-420 MUm and 280-530 MUm for OV90 and
      TOV112D cell lines, respectively. We envision that microfluidic funnels and
      single inlet multi-size spheroid (SIMSS) chips will find broad application in 3D
      biological assays where size-dependent responses are expected, including
      chemoresponse assays, photodynamic therapy assays, and other assays involving
      drug transport characterization in drug discovery.

PMID- 29211089
TI  - A deep conical agarose microwell array for adhesion independent three-dimensional
      cell culture and dynamic volume measurement.
AB  - Multicellular spheroids represent a well-established 3D model to study healthy
      and diseased cells in vitro. The use of conventional 3D cell culture platforms
      for the generation of multicellular spheroids is limited to cell types that
      easily self-assemble into spheroids because less adhesive cells fail to form
      stable aggregates. A high-precision micromoulding technique developed in our
      laboratory produces deep conical agarose microwell arrays that allow the
      cultivation of uniform multicellular aggregates, irrespective of the spheroid
      formation capacity of the cells. Such hydrogel arrays warrant a steady nutrient
      supply for several weeks, permit live volumetric measurements to monitor cell
      growth, enable immunohistochemical staining, fluorescence-based microscopy, and
      facilitate immediate harvesting of cell aggregates. This system also allows co
      cultures of two distinct cell types either in direct cell-cell contact or at a
      distance as the hydrogel permits diffusion of soluble compounds. Notably, we show
      that co-culture of a breast cancer cell line with bone marrow stromal cells
      enhances 3D growth of the cancer cells in this system.

PMID- 29211090
TI  - Addition of azomethine ylides to carbon-encapsulated iron nanoparticles.
AB  - The Prato reaction was applied for the covalent introduction of a variety of
      organic moieties onto carbon-encapsulated iron nanoparticles. The developed
      method is versatile and employs a broad range of commercially available
      reactants, including both aromatic and aliphatic aldehydes. The reported
      functionalization route provides high functionalization yields (ca. 12-21 wt%).

PMID- 29211091
TI  - Gold nanoparticle-based colorimetric biosensors.
AB  - Gold nanoparticles (AuNPs) provide excellent platforms for the development of
      colorimetric biosensors as they can be easily functionalised, displaying
      different colours depending on their size, shape and state of aggregation. In the
      last decade, a variety of biosensors have been developed to exploit the extent of
      colour changes as nano-particles (NPs) either aggregate or disperse, in the
      presence of analytes. Of critical importance to the design of these methods is
      that the behaviour of the systems has to be reproducible and predictable. Much
      has been accomplished in understanding the interactions between a variety of
      substrates and AuNPs, and how these interactions can be harnessed as colorimetric
      reporters in biosensors. However, despite these developments, only a few
      biosensors have been used in practice for the detection of analytes in biological
      samples. The transition from proof of concept to market biosensors requires
      extensive long-term reliability and shelf life testing, and modification of
      protocols and design features to make them safe and easy to use by the population
      at large. Developments in the next decade will see the adoption of user friendly
      biosensors for point-of-care and medical diagnosis as innovations are brought to
      improve the analytical performances and usability of the current designs. This
      review discusses the mechanisms, strategies, recent advances and perspectives for
      the use of AuNPs as colorimetric biosensors.

PMID- 29211092
TI  - Little Airways, Big Challenges: An overview of pediatric airway management.

PMID- 29211093
TI  - Effect of phase coarsening under melt annealing on the electrical performance of
      polymer composites with a double percolation structure.
AB  - The effect of phase coarsening on the evolution of the carbon black (CB)
      nanoparticle network under quiescent melt annealing and the electrical
      performance of polypropylene/polystyrene/carbon black (PP/PS/CB) composites with
      a double percolation structure was investigated. The results showed that when the
      CB content is low, the coarsening process of PP/PS/CB blends can be divided into
      two stages. In the first stage, the coarsening rate is fast before the formation
      of the CB nanoparticle network, and after annealing for a certain time, the
      evolution of the co-continuous morphology can drive the CB nanoparticles to self
      assemble into a complete nanoparticle network. In the second stage, the
      coarsening rate is slow after the formation of the CB nanoparticle network. When
      the CB content is high, the CB nanoparticle network can be maintained throughout
      the whole annealing process, so that the conductivity and morphology of the
      PP/PS/CB composites are stable. Moreover, the electrical conductivity of the
      PP/PS/CB composites greatly increases after annealing for a certain time, and a
      percolation threshold as low as 0.07 vol% can be obtained. These results reveal
      the relationship between the evolution of the morphology and the conductivity in
      the conductive polymer composites with a double percolation structure, and
      provide a more in-depth and comprehensive understanding of the double percolation
      structure.

PMID- 29211094
TI  - Preparation of MoS2/TiO2 based nanocomposites for photocatalysis and rechargeable
      batteries: progress, challenges, and perspective.
AB  - The rapidly increasing severity of the energy crisis and environmental
      degradation are stimulating the rapid development of photocatalysts and
      rechargeable lithium/sodium ion batteries. In particular, MoS2/TiO2 based
      nanocomposites show great potential and have been widely studied in the areas of
      both photocatalysis and rechargeable lithium/sodium ion batteries due to their
      superior combination properties. In addition to the low-cost, abundance, and high
      chemical stability of both MoS2 and TiO2, MoS2/TiO2 composites also show
      complementary advantages. These include the strong optical absorption of TiO2vs.
      the high catalytic activity of MoS2, which is promising for photocatalysis; and
      excellent safety and superior structural stability of TiO2vs. the high theoretic
      specific capacity and unique layered structure of MoS2, thus, these composites
      are exciting as anode materials. In this review, we first summarize the recent
      progress in MoS2/TiO2-based nanomaterials for applications in photocatalysis and
      rechargeable batteries. We highlight the synthesis, structure and mechanism of
      MoS2/TiO2-based nanomaterials. Then, advancements and strategies for improving
      the performance of these composites in photocatalytic degradation, hydrogen
      evolution, CO2 reduction, LIBs and SIBs are critically discussed. Finally,
      perspectives on existing challenges and probable opportunities for future
      exploration of MoS2/TiO2-based composites towards photocatalysis and rechargeable
      batteries are presented. We believe the present review would provide enriched
      information for a deeper understanding of MoS2/TiO2 composites and open avenues
      for the rational design of MoS2/TiO2 based composites for energy and environment
      related applications.

PMID- 29211098
TI  - Mesoscopic modelling and simulation of soft matter.
AB  - The deformability of soft condensed matter often requires modelling of
      hydrodynamical aspects to gain quantitative understanding. This, however,
      requires specialised methods that can resolve the multiscale nature of soft
      matter systems. We review a number of the most popular simulation methods that
      have emerged, such as Langevin dynamics, dissipative particle dynamics, multi
      particle collision dynamics, sometimes also referred to as stochastic rotation
      dynamics, and the lattice-Boltzmann method. We conclude this review with a short
      glance at current compute architectures for high-performance computing and
      community codes for soft matter simulation.

PMID- 29211101
TI  - Cholesteric ordering predicted using a coarse-grained polymeric model with
      helical interactions.
AB  - The understanding of cholesteric liquid crystals at a molecular level is
      challenging. Limited insights are available to bridge between molecular
      structures and macroscopic chiral organization. In the present study, we
      introduce a novel coarse-grained (CG) molecular model, which is represented by
      flexible chain particles with helical interactions (FCh), to study the liquid
      crystalline phase behavior of cholesteric molecules such as double strand DNA and
      alpha-helix polypeptides using molecular dynamics (MD) simulations. The isotropic
      cholesteric phase transitions of FCh molecules were simulated for varying chain
      flexibilities. A wall confinement was used to break the periodicity along the
      cholesteric helix director in order to predict the equilibrium cholesteric pitch.
      The left-handed cholesteric phase was shown for FCh molecules with right-handed
      chiral interactions, and a spatially inhomogeneous distribution of the nematic
      order parameter profile was observed in cholesteric phases. It was found that the
      chain flexibility plays an important role in determining the macroscopic
      cholesteric pitch and the structure of the cholesteric liquid crystal phase. The
      simulations provide insight into the relationship between microscopic molecular
      characteristics and the macroscopic phase behavior.

PMID- 29211102
TI  - Can sexual transmission support the enzootic cycle of Trypanosoma cruzi?
AB  - BACKGROUND: Trypanosoma cruzi circulates in sylvatic habitats, mainly through
      blood-feeding triatomines, although other routes also contribute to its
      dispersion. Sexual transmission of T. cruzi is an understudied topic, especially
      among wild mammals. Because of the difficulties inherent to field work,
      experimentally infected mice are frequently used to evaluate the transmission of
      T. cruzi. OBJECTIVE: This study aimed to evaluate the sexual transmission of T.
      cruzi in acutely infected mice. METHODS: Male and female mice in the acute phase
      of Chagas disease were mated with naive partners. Then, parasitological tests,
      immunohistochemistry, serological assays, and polymerase chain reaction (PCR)
      assays were used to detect infection. FINDINGS: Parasitological analysis showed
      trypomastigotes in the blood of 20% of the naive mice after mating with infected
      partners. Serological assays detected anti-T. cruzi antibodies in all naive
      females mated with infected males and in 60% of naive males mated with infected
      females. PCR showed T. cruzi nDNA bands for all naive mice mated with infected
      partners. The possibility of sexual transmission was also confirmed by
      visualisation of amastigotes in the testes. MAIN CONCLUSIONS: Our results
      demonstrate that sexual transmission of T. cruzi is an ordinary event that may
      contribute to maintenance of the parasite's enzootic cycle.

PMID- 29211103
TI  - Characterisation of a rare, reassortant human G10P[14] rotavirus strain detected
      in Honduras.
AB  - BACKGROUND: Although first detected in animals, the rare rotavirus strain
      G10P[14] has been sporadically detected in humans in Slovenia, Thailand, United
      Kingdom and Australia among other countries. Earlier studies suggest that the
      strains found in humans resulted from interspecies transmission and reassortment
      between human and bovine rotavirus strains. OBJECTIVES: In this study, a G10P[14]
      rotavirus genotype detected in a human stool sample in Honduras during the 2010
      2011 rotavirus season, from an unvaccinated 30-month old boy who reported at the
      hospital with severe diarrhea and vomiting, was characterised to determine the
      possible evolutionary origin of the rare strain. METHODS: For the sample detected
      as G10P[14], 10% suspension was prepared and used for RNA extraction and sequence
      independent amplification. The amplicons were sequenced by next-generation
      sequencing using the Illumina MiSeq 150 paired end method. The sequence reads
      were analysed using CLC Genomics Workbench 6.0 and phylogenetic trees were
      constructed using PhyML version 3.0. FINDINGS: The next generation sequencing and
      phylogenetic analyses of the 11-segmented genome of the G10P[14] strain allowed
      classification as G10-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. Six of the genes (VP1,
      VP2, VP3, VP6, NSP2 and NSP4) were DS-1-like. NSP1 and NSP5 were AU-1-like and
      NSP3 was T6, which suggests that multiple reassortment events occurred in the
      evolution of the strain. The phylogenetic analyses and genetic distance
      calculations showed that the VP7, VP4, VP6, VP1, VP3, NSP1, NSP3 and NSP4 genes
      clustered predominantly with bovine strains. NSP2 and VP2 genes were most closely
      related to simian and human strains, respectively, and NSP5 was most closely
      related to a rhesus strain. MAIN CONCLUSIONS: The genetic characterisation of the
      G10P[14] strain from Honduras suggests that its genome resulted from multiple
      reassortment events which were possibly mediated through interspecies
      transmissions.

PMID- 29211104
TI  - Surveillance of seroepidemiology and morbidity of Chagas disease in the Negro
      River, Brazilian Amazon.
AB  - BACKGROUND: Chagas disease in the Brazilian Amazon Region was previously regarded
      as an enzootic disease of wild animals. More recently, in situations where humans
      have penetrated the wild ecotope or where triatomines and/or wild animals
      (marsupials) have invaded human homes resulting in disease transmission, Chagas
      disease has come to be regarded as an anthropozoonosis. We found that the highest
      incidence of infection due to Trypanosoma cruzi and Chagas disease occurred among
      piassaba fibre gatherers and their families. OBJECTIVES: Considering the results
      of previous surveys, we conducted a new survey of piassaba gatherers and their
      families in the creeks of the Araca, Curuduri, Demini, Erere and Padauiri rivers,
      which are tributaries on the left bank of the Negro River, in the municipality of
      Barcelos; Barcelos-Caures highway; Negro River in Santa Isabel of the Negro
      River; and Marie River, on the right bank of the Negro River. METHODS: A
      questionnaire was applied to 482 piassaba gatherers and their families who
      accompanied them. We collected 5-mL blood samples (with permission from each
      subject), separated the serum, and performed serological tests using indirect
      immunofluorescence and conventional and recombinant enzyme-linked immunosorbent
      assays (ELISA). We performed brief clinical examination and electrocardiograms.
      Only 273 subjects attended our field base for detailed clinical examination and
      electrocardiogram. FINDINGS AND MAIN CONCLUSIONS: The questionnaire revealed that
      100% of the 482 patients recognised the triatomine Rhodnius brethesi, which they
      had seen in the piassaba plantation and 81% in their field huts. A total of 79%
      of subjects had previously been bitten by this vector and 21% did not know. The
      25 subjects seropositive for T. cruzi infection (5.2%) stated that they had been
      bitten more than 10 times by this insect. Of the 273 subjects who underwent
      electrocardiogram, 22% showed conditions that were possibly attributable to
      Chagas disease or other cardiovascular disease.

PMID- 29211105
TI  - Assessing the risk zones of Chagas' disease in Chile, in a world marked by global
      climatic change.
AB  - BACKGROUND: Vector transmission of Trypanosoma cruzi appears to be interrupted in
      Chile; however, data show increasing incidence of Chagas' disease, raising
      concerns that there may be a reemerging problem. OBJECTIVE: To estimate the
      actual risk in a changing world it is necessary to consider the historical vector
      distribution and correlate this distribution with the presence of cases and
      climate change. METHODS: Potential distribution models of Triatoma infestans and
      Chagas disease were performed using Maxent, a machine-learning method. FINDINGS:
      Climate change appears to play a major role in the reemergence of Chagas' disease
      and T. infestans in Chile. The distribution of both T. infestans and Chagas'
      disease correlated with maximum temperature, and the precipitation during the
      driest month. The overlap of Chagas' disease and T. infestans distribution areas
      was high. The distribution of T. infestans, under two global change scenarios,
      showed a minimal reduction tendency in suitable areas. MAIN CONCLUSION: The
      impact of temperature and precipitation on the distribution of T. infestans, as
      shown by the models, indicates the need for aggressive control efforts; the
      current control measures, including T. infestans control campaigns, should be
      maintained with the same intensity as they have at present, avoiding sylvatic
      foci, intrusions, and recolonisation of human dwellings.

PMID- 29211106
TI  - Trypanosoma cruzi strain TcIV infects raccoons from Illinois.
AB  - BACKGROUND: The northern limits of Trypanosoma cruzi across the territory of the
      United States remain unknown. The known vectors Triatoma sanguisuga and T.
      lecticularia find their northernmost limits in Illinois; yet, earlier screenings
      of those insects did not reveal the presence of the pathogen, which has not been
      reported in vectors or reservoir hosts in this state. OBJECTIVES: Five species of
      medium-sized mammals were screened for the presence of T. cruzi. METHODS: Genomic
      DNA was isolated from heart, spleen and skeletal muscle of bobcats (Lynx rufus, n
      = 60), raccoons (Procyon lotor, n = 37), nine-banded armadillos (Dasypus
      novemcinctus, n = 5), Virginia opossums (Didelphis virginiana, n = 3), and a red
      fox (Vulpes vulpes). Infections were detected targeting DNA from the kinetoplast
      DNA minicircle (kDNA) and satellite DNA (satDNA). The discrete typing unit (DTU)
      was determined by amplifying two gene regions: the Spliced Leader Intergenic
      Region (SL), via a multiplex polymerase chain reaction, and the 24Salpha
      ribosomal DNA via a heminested reaction. Resulting sequences were used to
      calculate their genetic distance against reference DTUs. FINDINGS: 18.9% of
      raccoons were positive for strain TcIV; the rest of mammals tested negative. MAIN
      CONCLUSIONS: These results confirm for the first time the presence of T. cruzi in
      wildlife from Illinois, suggesting that a sylvatic life cycle is likely to occur
      in the region. The analyses of sequences of SL suggest that amplicons resulting
      from a commonly used multiplex reaction may yield non-homologous fragments.

PMID- 29211107
TI  - Trypanosoma janseni n. sp. (Trypanosomatida: Trypanosomatidae) isolated from
      Didelphis aurita (Mammalia: Didelphidae) in the Atlantic Rainforest of Rio de
      Janeiro, Brazil: integrative taxonomy and phylogeography within the Trypanosoma
      cruzi clade.
AB  - BACKGROUND: Didelphis spp. are a South American marsupial species that are among
      the most ancient hosts for the Trypanosoma spp. OBJECTIVES: We characterise a new
      species (Trypanosoma janseni n. sp.) isolated from the spleen and liver tissues
      of Didelphis aurita in the Atlantic Rainforest of Rio de Janeiro, Brazil.
      METHODS: The parasites were isolated and a growth curve was performed in NNN and
      Schneider's media containing 10% foetal bovine serum. Parasite morphology was
      evaluated via light microscopy on Giemsa-stained culture smears, as well as
      scanning and transmission electron microscopy. Molecular taxonomy was based on a
      partial region (737-bp) of the small subunit (18S) ribosomal RNA gene and 708 bp
      of the nuclear marker, glycosomal glyceraldehyde-3-phosphate dehydrogenase
      (gGAPDH) genes. Maximum likelihood and Bayesian inference methods were used to
      perform a species coalescent analysis and to generate individual and concatenated
      gene trees. Divergence times among species that belong to the T. cruzi clade were
      also inferred. FINDINGS: In vitro growth curves demonstrated a very short log
      phase, achieving a maximum growth rate at day 3 followed by a sharp decline. Only
      epimastigote forms were observed under light and scanning microscopy.
      Transmission electron microscopy analysis showed structures typical to
      Trypanosoma spp., except one structure that presented as single-membraned,
      usually grouped in stacks of three or four. Phylogeography analyses confirmed the
      distinct species status of T. janseni n. sp. within the T. cruzi clade.
      Trypanosoma janseni n. sp. clusters with T. wauwau in a well-supported clade,
      which is exclusive and monophyletic. The separation of the South American T.
      wauwau + T. janseni coincides with the separation of the Southern Super
      Continent. CONCLUSIONS: This clade is a sister group of the trypanosomes found in
      Australian marsupials and its discovery sheds light on the initial
      diversification process based on what we currently know about the T. cruzi clade.

PMID- 29211108
TI  - Detection of occult hepatitis B in serum and oral fluid samples.
AB  - In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be
      detected in serum samples; however, oral fluid collection for detection of HBV
      DNA has not yet been explored, despite the availability of collection devices.
      Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)
      positive patients were collected for the amplification of the HBV polymerase
      gene. HBV DNA was detected in five serum and four oral fluid samples (the
      detection limit for oral fluid was 1.656 log IU/mL in paired serum). In
      conclusion, simple methodologies of sample collection and in-house polymerase
      chain reaction (PCR) allowed detection of HBV DNA, and these could be used to
      improve the diagnosis of OBI, especially in locations with limited resources.

PMID- 29211109
TI  - Metagenomic analysis reveals Hepatitis A virus in suspected yellow fever cases in
      Brazil.
AB  - Using a metagenomic approach, we identified hepatitis A virus among cases of
      acute febrile illnesses that occurred in 2008-2012 in Brazil suspected as yellow
      fever. These findings reinforce the challenge facing routine clinical diagnosis
      in complex epidemiological scenarios.

PMID- 29211110
TI  - Evaluation of melanin production by Sporothrix luriei.
AB  - There is a paucity of studies on the cell biology of Sporothrix luriei, the less
      common of the pathogenic Sporothrix species worldwide. The production of DHN
      melanin, eumelanin, and pyomelanin were evaluated on the mycelial and yeast forms
      of the S. luriei ATCC 18616 strain. The mycelial form of this species produced
      only pyomelanin, which protected the fungus against environmental stressors such
      as ultraviolet light, heat, and cold. The yeast form was unable to produce any of
      the tested melanin types. The lack of melanin in the parasitic form of S. luriei
      may be an explanation for its low frequency in human infections.

PMID- 29211111
TI  - Auditory skills of figure-ground and closure in air traffic controllers.
AB  - PURPOSE: To investigate the auditory skills of closure and figure-ground and
      factors associated with health, communication, and attention in air traffic
      controllers, and compare these variables with those of other civil and military
      servants. METHODS: Study participants were sixty adults with normal audiometric
      thresholds divided into two groups matched for age and gender: study group (SG),
      comprising 30 air traffic controllers and control group (CG), composed of 30
      other military and civil servants. All participants were asked a number of
      questions regarding their health, communication, and attention, and underwent the
      Speech-in-Noise Test (SIN) to assess their closure skills and the Synthetic
      Sentence Identification Test - Ipsilateral Competitive Message (SSI-ICM) in
      monotic listening to evaluate their figure-ground abilities. Data were compared
      using nonparametric statistical tests and logistic regression analysis. RESULTS:
      More individuals in the SG reported fatigue and/or burnout and work-related
      stress and showed better performance than that of individuals in the CG for the
      figure-ground ability. Both groups performed similarly and satisfactorily in the
      other hearing tests. The odds ratio for participants belonging in the SG was 5.59
      and 1.24 times regarding work-related stress and SSI-ICM (right ear),
      respectively. CONCLUSION: Results for the variables auditory closure, self
      reported health, attention, and communication were similar in both groups. The SG
      presented significantly better performance in auditory figure-ground compared
      with that of the CG. Self-reported stress and right-ear SSI-ICM were significant
      predictors of individuals belonging to the SG.

PMID- 29211112
TI  - Postswallow voice modification: compatibility with videofluoroscopy findings.
AB  - PURPOSE: Verify whether voice modification after swallowing is associated with
      videofluoroscopic examination data. METHODS: 27 patients with oropharyngeal
      dysphagia underwent recording of sustained phonation of vowel /a/ before and
      after swallowing during videofluoroscopy. The GRBAS scale and the wet voice
      parameter were used to evaluate the data. Videofluoroscopy results showed stasis
      of food in the valleculae and piriform recesses, laryngeal penetration, tracheal
      aspiration, and degree of dysphagia. RESULTS: Decreased dysphonia grade and
      asthenia and increased strain were observed after swallowing, with no difference
      for the wet voice parameter. Sensitivity and specificity of +/- 50% were observed
      for food stasis in the valleculae and piriform recesses. Sensitivity values of 80
      and 66-75% were observed for detection of laryngeal penetration and tracheal
      aspiration and modification of vocal strain, respectively. Negative predictive
      values of 77-91% were found for the three assessment parameters with no
      correlation with the degree of oropharyngeal dysphagia. CONCLUSION: Modification
      of the GRBAS scale parameters after swallowing showed good compatibility with
      videofluoroscopy findings.

PMID- 29211113
TI  - Orofacial Myofunctional Evaluation Protocol for older people: validity,
      psychometric properties, and association with oral health and age.
AB  - PURPOSE: To develop a comprehensive assessment protocol for identifying,
      classifying and grading changes in stomatognathic system components and functions
      of older people, to determine its psychometric properties and verify its
      association with oral health and age. METHODS: The content validity of the
      Orofacial Myofunctional Evaluation with Scores for Elders protocol (OMES-Elders)
      was established based on the literature. The protocol contains three domains:
      appearance/posture, mobility, and functions of the stomatognathic system. Eighty
      two healthy elder volunteers (mean age 69+/-7.24 years) were evaluated using the
      OMES-Elders. A test-screening for orofacial disorders (reference) was used to
      analyze the concurrent validity (correlation test), sensitivity, specificity and
      accuracy (Receiver Operating Characteristic Curve: ROC curve) of the OMES-Elders.
      The association of the OMES-Elders scores with the Oral Health Index (OHX) and
      age in the sample was tested. RESULTS: There was a significant correlation
      between the OMES-Elders and the reference test (p < 0.001). Reliability
      coefficients ranged from good (0.89) to excellent (0.99). The OMES-Elders
      protocol had a sensitivity of 82.9%, specificity of 83.3% and accuracy of 0.83.
      The scores of the protocol were significantly lower in individuals with worse
      oral health (OHX <= 61%), although individuals with adequate oral health (OHX >=
      90%) also had myofunctional impairments. The predictors OHX and age explained,
      respectively, 33% and 30% of the variance in the OMES-Elders total score.
      CONCLUSION: As the first specific orofacial myofunctional evaluation of older
      people, the OMES-Elders protocol proved to be valid, reliable and its total score
      was associated with oral health and age.

PMID- 29211114
TI  - Letter to the editor.

PMID- 29211115
TI  - Acute stress disorder and defense mechanisms: a study of physical trauma patients
      admitted to an emergency hospital.
AB  - INTRODUCTION: Acute stress disorder (ASD) encompasses a set of symptoms that can
      arise in individuals after exposure to a traumatic event. This study assessed the
      defense mechanisms used by victims of physical trauma who developed ASD. METHOD:
      This was a controlled cross-sectional study of 146 patients who suffered physical
      trauma and required hospitalization. A structured questionnaire was used to
      evaluate ASD symptoms based on DSM-5 diagnostic criteria, in addition to the
      Defense Style Questionnaire (DSQ). RESULTS: Ten participants (6.85%) received a
      positive diagnosis of ASD, and 136, (93.15%) a negative diagnosis. The majority
      of the sample consisted of men with median age ranging from 33.50 to 35.50. The
      most prevalent defense mechanisms among the 10 patients with ASD were
      cancellation and devaluation, which belong to the neurotic and immature factors,
      respectively. Positive associations between the presence of symptoms from
      criterion B of the DSM-5 and defense mechanisms from the DSQ were found. These
      included the mechanisms of undoing, projection, passive aggression, acting out,
      autistic fantasy, displacement, and somatization. CONCLUSION: Patients with ASD
      employed different defense mechanisms such as undoing and devaluation when
      compared to patients not diagnosed with ASD. These results mark the importance of
      early detection of ASD symptoms at a preventative level, thereby creating new
      possibilities for avoiding exacerbations related to the trauma, which represents
      an important advance in terms of public health.

PMID- 29211116
TI  - High burden and frailty: association with poor cognitive performance in older
      caregivers living in rural areas.
AB  - INTRODUCTION: Older caregivers living in rural areas may be exposed to three
      vulnerable conditions, i.e., those related to care, their own aging, and their
      residence context. OBJECTIVE: To analyze the association of burden and frailty
      with cognition performance in older caregivers in rural communities. METHOD: In
      this cross-sectional survey, 85 older caregivers who cared for dependent elders
      were included in this study. Global cognition (Addenbrooke's Cognitive
      Examination - Revised; Mini Mental State Examination), burden (Zarit Burden
      Interview) and frailty (Fried's frailty phenotype) were assessed. All ethical
      principles were observed. RESULTS: Older caregivers were mostly women (76.7%);
      mean age was 69 years. Cognitive impairment was present in 15.3%, severe burden
      in 8.2%, frailty in 9.4%, and pre-frailty in 52.9% of the older caregivers. More
      severely burdened or frail caregivers had worse cognitive performance than those
      who were not, respectively (ANOVA test). Caregivers presenting a high burden
      level and some frailty degree (pre-frail or frail) simultaneously were more
      likely to have a reduced global cognition performance. CONCLUSION: A significant
      number of older caregivers had low cognitive performance. Actions and resources
      to decrease burden and physical frailty may provide better cognition and well
      being, leading to an improved quality of life and quality of the care provided by
      the caregivers.

PMID- 29211117
TI  - Adaptation and validation of the Melbourne Decision Making Questionnaire to
      Brazilian Portuguese.
AB  - INTRODUCTION: Decision making (DM) is among the most important abilities for
      everyday functioning. However, the most widely used measures of DM come from
      behavioral paradigms, whose ecological validity and standalone use has been
      criticized in the literature. Though these issues could be addressed by the use
      of DM questionnaires as a complementary assessment method, no such instruments
      have been validated for use in Brazilian Portuguese. Therefore, the aim of this
      study was to conduct the translation and validation of the Melbourne Decision
      Making Questionnaire (MDMQ) for use in a Brazilian population. METHODS: The
      adaptation of the MDMQ involved the following steps: translation, back
      translation, expert review and pilot study. These steps were followed by factor
      analysis and internal consistency measurements, which led to the exclusion of 4
      items from the scale. The 18-item version of the MDMQ was then administered to a
      validation sample consisting of healthy adults, as well as patients with bipolar
      disorder (BD) and major depressive disorder (MDD). RESULTS: The instrument
      displayed good internal consistency, with the hypervigilance subscale showing the
      lowest, though still acceptable, Cronbach's alpha value. Its factor structure was
      comparable to that of the original MDMQ according to confirmatory factor
      analysis. Nevertheless, the MDMQ was sensitive to both depression severity and
      the presence of MDD and BD, both of which are known to have an impact on DM
      ability. CONCLUSION: The version of the MDMQ produced in the present study may be
      an important addition to neuropsychological assessment batteries with a focus on
      DM and related abilities.

PMID- 29211118
TI  - Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A
      Systematic Scoping Review.
AB  - Although the biological properties of mesenchymal stem cells (MSC) are well
      characterized in vitro, MSC clinical application is still far away to be
      achieved, mainly due to the need of xenogeneic substances for cell expansion,
      such as fetal bovine serum (FBS). FBS presents risks regarding pathogens
      transmissions and internalization of animal's proteins, which can unleash
      antigenic responses in patients after MSC implantation. A wide range of venous
      blood derivatives (VBD) has been reported as FBS substitutes showing promising
      results. Thus, the aim of this study was to conduct a systematic scoping review
      to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion.
      The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME,
      Cochrane library up to January 2016. The keywords were selected using MeSH and
      entry terms. Two independent reviewers scrutinized the records obtained
      considering specific inclusion criteria. The included studies were evaluated in
      accordance with a modified Arksey and O' Malley's framework. From 184 found
      studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were
      presented in most of these studies. Overall, VBD allowed for either, maintenance
      of MCS's fibroblast-like morphology, high proliferation, high colony-formation
      ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements
      presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free
      serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated
      heterogeneity was observed between the carried out protocols for VBD isolation
      did not allowing for direct comparisons between the included studies.

PMID- 29211119
TI  - Study of Microbial Interaction Formed by "Candida krusei" and "Candida glabrata":
      "In Vitro" and "In Vivo" Studies.
AB  - Recently, the non-albicans Candida species have become recognized as an important
      source of infection and oral colonization by association of different species in
      a large number of immunosuppressed patients. The objective of this study was to
      evaluate the interactions between C. krusei and C. glabrata in biofilms formed in
      vitro and their ability to colonize the oral cavity of mouse model. Monospecies
      and mixed biofilms were developed of each strain, on 96-well microtiter plates
      for 48 h. These biofilms were analyzed by counting colony-forming units (CFU/mL)
      and by determining cell viability, using the XTT hydroxide colorimetric assay.
      For the in vivo study, twenty-four mice received topical applications of
      monospecie or mixed suspensions of each strain. After 48 h, yeasts were recovered
      from the mice and quantified by CFU/mL count. In the biofilm assays, the results
      for the CFU/mL count and the XTT assay showed that the two species studied were
      capable of forming high levels of in vitro monospecie biofilm. In mixed biofilm,
      the CFU of C. krusei increased (p=0.0001) and C. glabrata decreased (p=0.0001).
      The metabolic activity observed in XTT assay of mixed biofilm was significantly
      reduced compared with a single C. glabrata biofilm (p=0.0001). Agreeing with CFU
      in vitro count, C. glabrata CFU/mL values recovered from oral cavity of mice were
      statistically higher in the group with single infection (p=0.0001) than the group
      with mixed infection. We concluded that C. krusei inhibits C. glabrata and takes
      advantage to colonize the oral cavity and to form biofilms.

PMID- 29211120
TI  - Cell Derived Microparticles in Gingival Crevicular Fluid from Periodontitis
      Patients with Type 2 Diabetes.
AB  - Cell-derived microparticles (MPs) have been described as vital contributors to
      the inflammatory process. However, its role in the periodontal disease
      pathogenesis remains unclear. Therefore, we aimed to detect the presence
      neutrophil (CD66b+) and platelet (CD41b+) derived microparticles in gingival
      crevicular fluid from individuals having periodontitis aggravated by type 2
      diabetes. Twelve patients (56.2 +/-7.2 yrs) with severe form of chronic
      periodontitis aggravated by type 2 diabetes were included. Clinical and metabolic
      data were gathered. Gingival crevicular fluid was collected using filter strips
      from deep and shallow sites. MPs were detected by flow cytometry according to
      their size (< 1 um) and the expression of surface markers (CD66b for neutrophil
      derived MPs and CD41b for platelet-derived MPs). All samples were positive for
      the antibodies. Median levels of CD66b+ MPs and CD41b+ MPs were, respectively,
      3,677.0 (2,553.2 - 9,059.8) MP/uL and 520.7 (432.9 - 766.1) MP/uL in deep sites.
      In shallow sites, the corresponding values were 2,644.9 (1,451.5 - 3,858.9) MP/uL
      and 371.2 (287.2 - 692.7) MP/uL. There was no significant difference between deep
      and shallow sites (p>0.05). In conclusion, this study reported the presence of
      neutrophil and platelet derived microparticles in gingival crevicular fluid from
      individuals having severe periodontitis and type 2 diabetes.

PMID- 29211121
TI  - Evolution of Periodontal Disease: Immune Response and RANK/RANKL/OPG System.
AB  - The aim of this study was to evaluate markers of bone loss and immune response
      present in evolution of periodontal disease. One hundred and two Wistar rats were
      divided into three animals groups: PD0, without ligation and PD15 days and PD60
      days, submitted to ligation placement with a sterile 3-0 silk cord in the
      cervical region of the upper first molar on both sides. Samples were obtained
      from the gingival tissue for histomorphometric analysis, immunohistochemical
      analysis of RANK, RANKL, OPG, characterization of the inflammatory infiltrate,
      quantification of nitric oxide, MCP-1, RANTES, IP10 chemokines, and expression of
      the TGF-b1, VEG, and bFGF. The number of inflammatory cells in gingival tissue
      was higher in PD60 samples. The collagen content and the area occupied by
      birefringent collagen fibers were lower for PD60. Differential leukocyte counting
      showed that there was a significantly higher polymorphonuclear influx in group
      PD15, while PD60 showed a greater number of lymphocytes. PD60 showed higher
      RANTES, IP-10, MCP-1 gene transcripts, as well as a higher nitric oxide
      concentration. Clinical evaluation revealed that the PD60 group presented an
      increase in furcal area. In conclusion, in this animal model the increase of
      RANK/RANKL and HGF markers is related to a specific immune response, and probably
      contributed to the evolution of periodontal disease. Investigating the effect of
      these biomarkers can help in targeted therapy for bone resorption, since blocking
      these can inhibit bone loss.

PMID- 29211122
TI  - Actinomycosis is not Frequent in the Periapex But is a Persistent Lesion.
AB  - Periapical actinomycosis caused by a gram-positive anaerobic pathogen
      characterizes a typical extra-radicular infection. This study determined the
      frequency and correlated the content of bacteria colonies with the of periapical
      actinomycosis size. The study comprised a total of 218 periapical lesions (PL)
      (cysts, granulomas or abscess). The specimens embedded in paraffin were sliced
      into 4-um sections and stained with hematoxylin-eosin, Gram, Periodic Acid-Schiff
      (PAS) and Grocott's stain. The presence of bacterial colonies composed of
      filamentous structures labeled with the histochemical stains were described as
      Actinomyces, and for each case, the bacterial colonies were counted and measured.
      The correlation between the number and size of bacterial colonies and the size of
      PL was tested using Pearson's adjusted correlation coefficient. From 218 PL,
      bacterial colonies were identified in 64 biopsies. Seven cases (0.3%) fulfill the
      criteria for diagnosis of periapical actinomycosis. All of cases were therapy
      resistant and did not showed periapical repair after 12 months of follow-up.
      Periapical surgery or dental extraction was performed. The correlation test
      indicated no correlation between the number of bacterial colonies and the lesion
      size (p=0.752, r=-0.148). However, a larger bacterial colony size generally
      resulted in a larger periapical lesion (P=0.000, r=0.657). The frequency of
      periapical actinomycosis was low, and this lesion should be included in the
      differential diagnosis of PL. The size of the Actinomyces colonies seemed to
      contribute to increase the size of the periapical lesion.

PMID- 29211123
TI  - Peri-Implant Bone Loss of External Hexagon and Morse Taper in Patients Wearing
      Immediately Loaded Overdentures.
AB  - The aim of this study was to evaluate the peri-implant bone loss of External
      Hexagon (EH) and Morse Taper (MT) implants in patients wearing immediately loaded
      mandibular overdentures during a 1-year follow-up. This is a non-randomized
      controlled clinical trial including 18 MT and 22 EH implants. Periapical
      radiographs were taken after overdentures insertion and following 1 year. The
      peri-implant bone loss was assessed through digitalization and analysis of the
      radiographs in the software Corel DRAW X7. For this, measurement from implant
      platform to residual ridge at mesial and distal surfaces of each implant was
      conducted. The results showed high success rate in the groups EH (100%) and MT
      (94.4%). For peri-implant bone levels, it was found significant difference
      between the groups (p=0.032) and greater bone loss was observed in the group EH.
      In general, bone loss was 0.85mm (+/-0.82) for EH and 0.10mm (+/-1.0) for MT. It
      was concluded that greater bone loss occurred in the group EH in comparison to
      the group MT after a 1-year follow-up.

PMID- 29211124
TI  - Association of Oral Lichen Planus and Electrocardiographic P-Wave Dispersion - An
      Original Research.
AB  - Lichen planus (LP) is considered to be a T-cell-mediated inflammatory disorder.
      Inflammation is considered to produce disturbances of lipid metabolism which may
      affect the myocardium. Increased P-Wave Dispersion (PWD) is demonstrated as an
      independent risk factor for developing atrial fibrillation (AF). Hence the
      present study has been conducted to explore the possible relationship of oral
      lichen planus (OLP) with AF by the evaluation of PWD. Twelve-lead
      electrocardiographs (ECG) were obtained from 45 OLP patients and 45 age and
      gender-matched healthy controls. The P-wave durations (Pmax and Pmin) were
      calculated in all 12 leads. The difference between Pmax and Pmin was defined as P
      Wave Dispersion (PWD). After the PWD was recorded, the results were statistically
      analyzed. The study showed that PWD increased on surface ECG measurements in OLP
      patients who were otherwise asymptomatic in relation to cardiac conditions. The p
      value obtained was <0.001 which was highly significant. The present study
      suggests a highly statistically significant association of OLP with increased P
      wave dispersion. Hence the patients with OLP should undergo cardiac evaluation
      and follow up for early detection of atrial fibrillation.

PMID- 29211125
TI  - Oxygen Saturation in the Dental Pulp of Maxillary and Mandibular Molars - Part 2.
AB  - This study determined the oxygen saturation (SaO2) in dental pulp of healthy
      maxillary and mandibular molars. Mean of SaO2 was evaluated in 112 maxillary and
      mandibular molars using pulse oximetry. Quantitative variables were described by
      mean and standard deviation. Variables with symmetric distribution were compared
      by Student t test and Mann-Whitney test. Pearson's correlation coefficient was
      used to correlate quantitative variables. Analysis of variance was used to assess
      differences in SaO2 levels between the molar groups, followed by post-hoc Tukey.
      The significance level established at p<0.05. Mean of oxygen saturation for the
      112 molar dental pulps was 85.09%. There was no significant correlation (r=
      0.007; p=0.977) between the mean of SaO2 of molar pulps with patient's indicator
      finger (92.89%). There was a significant difference (p=0.037) between the mean of
      SaO2 of the first (85.76%) and second maxillary molars (81.87%), and it was not
      significant (p=0.1775) between the first and second mandibular molars. Maxillary
      molars had lower pulpal SaO2 (83.59%) than mandibular molars (86.89%) (p=0.018).
      The mean of the patient's response time to the cold stimulus was 1.12 s
      (maxillary molars 1.25 s and mandibular molars 0.99 s)(p=0.052). There was no
      significant correlation between the time response of the patient to the cold
      stimulus and the SaO2 for molars. The mean oxygen saturation level was 85.09%.
      The mandibular molars presented higher SaO2 level than maxillary molars.

PMID- 29211126
TI  - Effect of Reciprocating Systems and Working Lengths on Apical Microcrack
      Development: a micro-CT Study.
AB  - The objective of this study was to evaluate the effect of root canal preparation
      with single-file reciprocating systems at different working lengths on the
      development of apical microcracks using micro-computed tomographic (micro-CT)
      imaging. Forty extracted human mandibular incisors were randomly assigned to 4
      groups (n=10) according to the systems and working length used to prepare the
      root canals: Group A - WaveOne Gold at apical foramen (AF), Group B - WaveOne
      Gold 1 mm short of the AF (AF-1 mm), Group C - Unicone (AF) and Group D - Unicone
      (AF-1 mm). Micro-CT scanning was performed before and after root canal
      preparation at an isotropic resolution of 14 um. Then, three examiners assessed
      the cross-sectional images generated to detect microcracks in the apical portion
      of the roots. Apical microcracks were visualized in 3, 1, 1, and 3 specimens in
      groups A, B, C, and D, respectively. All these microcracks observed after root
      canal preparation already existed prior to instrumentation, and no new apical
      microcrack was detected. For all groups, the number of slices presenting
      microcracks after root canal preparation was the same as before canal
      preparation. Root canal preparation with WaveOne Gold and Unicone, regardless of
      the working length, was not associated with apical microcrack formation.

PMID- 29211127
TI  - Evaluation of Stress Distribution in Endodontically Weakened Teeth Restored with
      Different Crown Materials: 3D-FEA Analysis.
AB  - This study evaluated the stress distribution in endodontically treated teeth,
      weakened (W) or not weakened (NW), restored with different materials of
      prosthetic crown using 3D-FEA. Models of a maxillary canine were constructed
      based on micro-CT images and divided into the groups: G1 (control) - sound tooth;
      G2 to G7 - endodontically treated teeth restored with glass fiber post (GFP);
      which G2 to G4 simulated NW root and G5 to G7 simulated W root. For crown
      material the teeth were restored with: G2 and G5: metallic coping and ceramic
      veneering, G3 and G6: zirconia coping and ceramic veneering, G4 and G7: alumina
      coping and ceramic veneering. Load of 180 N was applied at the incisal third of
      lingual surface at 45o. Models were supported by the periodontal ligament
      (x=y=z=0). The von Mises stress (VMS) values were calculated. The W teeth
      presented higher VMS at coping when compared to NW teeth and group G1 showed
      lower VMS value. For crown material, for both W or NW teeth, increasing VMS was
      found at metallic, zirconia and alumina coping, respectively. Metallic coping
      showed a better performance despite its unfavorable esthetics, suggesting as an
      appropriate material for prosthetic restoration of endodontically treated teeth.

PMID- 29211128
TI  - In-Office Tooth Bleaching for Adolescents Using Hydrogen Peroxide-Based Gels:
      Clinical Trial.
AB  - The aim of the present study was to evaluate colorimetric changes and tooth
      sensitivity in adolescents and young patients submitted to tooth bleaching with
      20% and 35% hydrogen peroxide. A randomized, controlled, clinical trial was
      conducted with 53 patients aged 11 to 24 years who were allocated to groups based
      on the use of the following commercial products: Whiteness HP - FGM(r) (35%
      hydrogen peroxide); Whiteness HP Blue Calcium - FGM(r) (35% hydrogen peroxide);
      and Whiteness HP Blue Calcium - FGM(r) (20% hydrogen peroxide). After the
      bleaching procedure, the visual analog scale was used to measure tooth
      sensitivity and the Vita Classical Shade guide was used to determine changes in
      tooth color. Statistical analysis involved the Friedman, Kruskal-Wallis and
      Student-Newman-Keuls tests, with p<=0.05 considered indicative of statistical
      significance. The addition of calcium contributed to a reduction in tooth
      sensitivity, especially when the lower concentration of hydrogen peroxide (20%)
      was used. Tooth sensitivity occurred in a transitory way and did not influence
      the tooth bleaching process. Significant differences in color were found after
      each of the two bleaching sessions. In-office tooth bleaching was considered an
      effective method for adolescents and young adults. Further studies in this
      population are necessary in order to fully evaluate the effects of bleaching in
      young teeth.

PMID- 29211129
TI  - Influence of Different Concentration and Ratio of a Photoinitiator System on the
      Properties of Experimental Resin Composites.
AB  - The aim in this study was to evaluate the influence of different ratio of
      camphorquinone/tertiary amine concentration on the flexural strength (FS),
      elastic modulus (EM), degree of conversion (DC), yellowing (YL), water sorption
      (WS) and water solubility (WSL) of experimental composites. Thus, acrylate blends
      were prepared with different camphorquinone (CQ) and amine (DABE) concentrations
      and ratios by weight: (CQ/DABE%): 0.4/0.4% (C1), 0.4/0.8% (C2), 0.6/0.6% (C3),
      0.6/1.2% (C4), 0.8/0.8% (C5), 0.8/1.6% (C6), 1.0/1.0% (C7), 1.0/2.0% (C8),
      1.5/1.5% (C9), 1.5/3.0% (C10). For the FS and EM, rectangular specimens (7x2x1
      mm, n=10) were photo-activated by single-peak LED for 20 s and tested at Instron
      (0.5 mm/min). Then, the same specimens were evaluated by FTIR for DC measurement.
      For YL, disks (5x2 mm, n=10) were prepared, light-cured for 20 s and evaluated in
      spectrophotometer using the b aspect of the CIEL*a*b* system. For WS and WSL, the
      volume of the samples was calculated (mm3). For WS and WSL, composites disks
      (5x0.5 mm, n=5) were prepared. After desiccation, the specimens were stored in
      distilled water for 7 days and again desiccated, in order to measure the WS and
      WSL. Data were submitted to one-way ANOVA and Tukey's test (5%). The groups C8,
      C9 and C10 showed higher DC, EM and YL means, compared to other composites.
      Therefore, the FS and WS values were similar among all groups. Also, C1, C2 and
      C3 presented higher WSL in 7 days, compared to other composites. In general,
      higher concentrations of camphorquinone promoted higher physical-mechanical
      properties; however, inducing higher yellowing effect for the experimental
      composites.

PMID- 29211130
TI  - Dentin Sealing and Bond Strength Evaluation of Hema-Free and Multi-Mode Adhesives
      to Biomodified Dentin.
AB  - This study evaluated the effect of dentin biomodification on the bond strength
      (BS) and sealing ability (SA) of HEMA-free and multi-mode adhesives after 24 h
      and 6 months of water storage. Four adhesives were tested: two multi-mode
      (Scotchbond Universal - SU, and Prime & Bond Elect - PB) and two HEMA-free (All
      Bond 3 - AB, and G-Aenial - GA). Human third molars were selected and dentin was
      treated with two cross-linking agents (5% glutaraldehyde and 6.5%
      proanthocyanidin-rich grape seed extract - PACs) for 10 min or kept untreated
      (control group) (n=6). Teeth were sectioned and prepared for BS test and SA
      analysis. The SA measurements were taken with the presence of smear layer
      (minimum permeability), EDTA treatment (maximum permeability), PACs application,
      adhesive application and after 6 months of water storage. BS data were analyzed
      by Proc Mixed and Tukey-Kramer test (alpha=5%). PACs application increased the BS
      for all adhesives tested at 24 h. However, BS decreased for SU and AB after six
      months. In general, multi-mode adhesives (SU and PB) did not differ from AB HEMA
      free. GA presented the lowest BS values at both times of evaluation. Dentin
      permeability was reduced after PACs application and remained the same after 6
      months, regardless adhesive application. PACs can increase the BS regardless the
      type of adhesive, however only for PB and GA the BS kept stable after 6-months of
      water storage. PACs was able to seal the dentin as the minimum permeability and
      also remained stable after 6 months.

PMID- 29211131
TI  - In Vitro Evaluation of the Remineralizing Potential and Antimicrobial Activity of
      a Cariostatic Agent with Silver Nanoparticles.
AB  - Cariostatic treatment has been shown to successfully arrest caries. However, it
      blackens the carious tooth structure. This study evaluated the effects of an
      experimental cariostatic agent with silver nanoparticles (Ag-Nano) using
      microhardness (MH) and microbiological tests. The cariostatic agents tested were:
      Saforide(r), Cariestop(r), Ancarie(r) and Ag-Nano. Sixty-six samples from
      deciduous enamel were submitted to initial (after pH cycling to obtain initial
      caries-like lesion) and final (after cariostatic application) MH testing and %MH
      values were calculated. After longitudinal sectioning, internal (I) MH was
      evaluated. Strains of Streptococcus mutans, Escherichia coli, and Enterococcus
      faecalis in brain-heart infusion culture were treated with the cariostatic
      agents. Agar diffusion tests (ADTs) were performed and minimum inhibitory
      concentrations were determined. The statistical tests used were: Kruskal-Wallis
      and Dunn (%MD; ADT; MIC) and ANOVA followed by Tukey's test (I-MH) (p<0.05). The
      %MH of Saforide(r) was significantly greater than that of Ag-Nano (p<0.05).
      Internal MH showed progressive improvement in the enamel remineralization for all
      cariostatic tested. In ADTs showed greater inhibition of S. mutans, E. faecalis,
      and E. coli by Saforide(r) than by Ancarie(r) and Ag-Nano. Ag-Nano was able to
      inhibit 100% microorganism growth at a lower concentration than required for the
      other agents. It was concluded that Ag-Nano treatment promoted remineralization
      of deciduous tooth enamel with initial caries-like lesion and bactericidal
      activity.

PMID- 29211132
TI  - Effect of the Bis-Dimethylamino Benzydrol Coinitiator on the Mechanical and
      Biological Properties of a Composite.
AB  - To examine the effect of the alternative coinitiator 4,4'bis dimethylamino
      benzydrol (BZN) in degree of conversion (DC), mechanical and biological
      properties of experimental composites. The coinitiator BZN was used in three
      concentrations (0.2, 0.5 and 1.2%), and the coinitiator DMAEMA was used as
      control at the same concentrations as above. The molar concentration of
      camphorquinone (CQ) and coinitiators was kept constant (1:1). The composites were
      manipulated and submitted to microhardness test (VHN), flexural and compressive
      strength (in MPa), elastic modulus (GPa), DC (FT-IR) and in vitro cytotoxicity
      (against 3T3 fibroblastic cells) of the experimental resins. Data were subjected
      to two-way ANOVA and Tukey post-test (alpha=0.05). The experimental composite
      resin with BZN showed higher DC values compared to control DMAEMA groups. For the
      mechanical properties, microhardness values were higher in BZN groups; flexural
      strength and elastic modulus were similar between all the groups. Compressive
      strength for groups BZN0.5 and DMAEMA0.5 were not statistically different, being
      the lowest values attributed to group BZN0.2. The experimental resins with BZN
      and DMAEMA were considered nontoxic against 3T3 fibroblasts. The inclusion of the
      coinitiator BZN in experimental composites was considered nontoxic against 3T3
      fibroblast cells, without compromising DC and mechanical properties.

PMID- 29211133
TI  - A 12-Year Retrospective Study of Avulsion Cases in a Public Brazilian Dental
      Trauma Service.
AB  - This study assessed the epidemiological characteristics and management of the
      permanent teeth avulsion cases attended in a Brazilian dental trauma service from
      December 2005 to August 2016. A retrospective study was conducted of case records
      of 93 patients involving 139 avulsed teeth. Data included sex, age, trauma
      etiology, location of the accident, number and position of avulsed teeth, and
      presence and type of associated traumatic lesions. Management of the avulsed
      teeth was addressed as: time elapsed until teeth were retrieved from the
      accident's location; teeth's cleaning method and storage media; time elapsed
      until seeking treatment and replantation. The majority of the patients were
      children from 6-10 (31.2%) and 11-15 years old (26.9%). Male patients were more
      affected than female. Bicycle accident was the main etiological factor (31.2%).
      In 56 (60.2%) cases, traumatic lesions to neighboring teeth were present. In 55
      (59.1%) cases, lesions to adjacent soft tissues were reported. In 82 (88.2%)
      cases, patients requested treatment at the same day of the accident. Sixty-four
      teeth (46.0%) were immediately retrieved and 28 (20.1%) were not found. Forty-two
      teeth (30.2%) were kept dry. Only one tooth (0.7%) was immediately replanted at
      the accident's site, while 51 teeth (36.7%) were not replanted. Numerous avulsed
      teeth were inappropriately managed and immediate replantation was not frequent.
      Public policies must be created to raise awareness towards the particularities of
      avulsion cases.

PMID- 29211134
TI  - Gastrointestinal helminths of two populations of wild pigeons (Columba livia) in
      Brazil.
AB  - The present study analyzed gastrointestinal helminth communities in 265 wild
      pigeons (Columba livia) living in the municipalities of Sao Paulo and Tatui,
      state of Sao Paulo, Brazil, over a one-year period. The birds were caught next to
      grain storage warehouses and were necropsied. A total of 790 parasites comprising
      one nematode species and one cestode genus were recovered from 110 pigeons, thus
      yielding an overall prevalence of 41.5%, mean intensity of infection of 7.2 +/-
      1.6 (range 1-144) and discrepancy index of 0.855. Only 15 pigeons (5.7%)
      presented mixed infection. The helminths isolated from the birds were Ascaridia
      columbae (Ascaridiidae) and Raillietina sp. (Davaineidae). The birds' weights
      differed according to sex but this did not influence the intensity of infection.
      The overall prevalence and intensity of infection did not differ between the
      sexes, but the prevalence was higher among the birds from Tatui (47.8%). The
      gastrointestinal helminth community of C. livia was characterized in the two
      areas studied and parasite homogeneity was observed over the 12 months analyzed
      at both locations. These results make contributions to the current literature on
      health aspects of wild C. livia populations.

PMID- 29211135
TI  - Longitudinal evaluation of humoral immune response and merozoite surface antigen
      diversity in calves naturally infected with Babesia bovis, in Sao Paulo, Brazil.
AB  - Babesiosis is an economically important infectious disease affecting cattle
      worldwide. In order to longitudinally evaluate the humoral immune response
      against Babesia bovis and the merozoite surface antigen diversity of B. bovis
      among naturally infected calves in Taiacu, Brazil, serum and DNA samples from 15
      calves were obtained quarterly, from their birth to 12 months of age. Anti-B.
      bovis IgG antibodies were detected by means of the indirect fluorescent antibody
      test (IFAT) and enzyme-linked immunosorbent assay (ELISA). The polymerase chain
      reaction (PCR) was used to investigate the genetic diversity of B. bovis, based
      on the genes that encode merozoite surface antigens (MSA-1, MSA-2b and MSA-2c).
      The serological results demonstrated that up to six months of age, all the calves
      developed active immunity against B. bovis. Among the 75 DNA samples evaluated,
      2, 4 and 5 sequences of the genes msa-1, msa-2b and msa-2c were obtained. The
      present study demonstrated that the msa-1 and msa-2b genes sequences amplified
      from blood DNA of calves positive to B. bovis from Taiacu were genetically
      distinct, and that msa-2c was conserved. All animals were serologically positive
      to ELISA and IFAT, which used full repertoire of parasite antigens in despite of
      the genetic diversity of MSAs.

PMID- 29211136
TI  - Surveillance System for Risk and Protective Factors for Chronic Diseases by
      Telephone Survey (Vigitel): changes in weighting methodology.
AB  - OBJECTIVE: to introduce the methodology used to calculate post-stratification
      weights of the 2012 Surveillance System for Risk and Protective Factors for
      Chronic Diseases by Telephone Survey (Vigitel) and to compare the trends of
      indicators estimated by cell-by-cell weighting and raking methods. METHODS: in
      this panel of cross-sectional studies, the prevalences of smokers, overweight,
      and intake of fruits and vegetables from 2006 to 2012 were estimated using the
      cell-by-cell weighting and raking methods. RESULTS: there were no differences in
      time trends of the indicators estimated by both methods, but the prevalence of
      smokers estimated by the raking method was lower than the estimated by cell-by
      cell weighting, whilst the prevalence of fruit and vegetable intake was higher;
      for overweight, there was no difference between the methods. CONCLUSION: raking
      method presented higher accuracy of the estimates when compared to cell-by-cell
      weighting method, proving to be most convenient, although it presents register
      coverage bias.

PMID- 29211137
TI  - Breast cancer screening in Brazil: an assessment of supply and use of Brazilian
      National Health System health care network for the period 2010-2012.
AB  - OBJECTIVE: to assess the supply and use of procedures for early detection,
      diagnosis and surgeries of breast cancer in the Brazilian National Health System
      (SUS). METHODS: descriptive study using data from SUS Ambulatory Care and
      Hospital Information Systems, and from the National Register of Health Care
      Facilities; the indicators of supply and use of these services in Brazil and its
      macroregions for 2010-2012 were calculated. RESULTS: the ratio mammography
      equipment and female population/100 thousand remained stable (1.5), ranging from
      1.0 in the North region to 2.0 in the South; the ratio mammograms and female
      population/100 thousand increased in all macroregions; there was a low proportion
      of diagnostic procedures when compared to the estimates (biopsy, 11.5%; core
      biopsy, 16.6% in women aged 50-69 years); the installed capacity decreased,
      however the production increased, and the supply (3,995,627) was below the
      necessary to cover 70% (7,785,415). CONCLUSION: there are inequalities in supply
      and use of the procedures in the Brazilian regions, and the access to diagnosis
      is worrisome.

PMID- 29211138
TI  - Factors associated with homicide in Manaus, Amazonas, Brazil, 2014.
AB  - OBJECTIVE: to identify characteristics, magnitude and factors associated with
      homicide in Manaus-AM, Brazil. METHODS: cross-sectional study, with data from the
      Mortality Information System (SIM); homicide rates and odds ratio (OR) were
      estimated, comparing to other external causes, for 2014; logistic regression was
      used. RESULTS: of the 1,657 violent deaths, 913 were due to homicide; homicide
      rate was of 55.8/100 thousand inhabitants (95%CI 52.1;59.7); odds ratio was
      higher among males (OR 3.4; 95%CI 2.3;5.1) when compared with females; among
      single (OR 1.6; 95%CI 1.1;2.5) and widowed individuals (OR 4.1; 95%CI 1.1;15.6),
      when compared with married individuals; at night/early hours (OR 2.1; 95%CI
      1.6;2.9) and in the afternoon (OR 1.7; 95%CI 1.2;2.4), when compared with the
      morning period; the probability was higher among individuals under 35 years, with
      less schooling. CONCLUSION: homicide mortality in Manaus was high, especially
      among males and young individuals with less schooling.

PMID- 29211139
TI  - Use of psychotropic medications in adults and elderly living in Campinas, Sao
      Paulo, Brazil: cross-sectional population-based study.
AB  - OBJECTIVE: to estimate the prevalence of use of psychotropic medicines and
      associated factors in adults and elderly, and to identify the main classes used.
      METHODS: cross-sectional population-based study, conducted in Campinas-SP, Brazil
      (January/2008-April/2009); chi-square Rao-Scott test and Poisson multiple
      regression were applied. RESULTS: the study included 2,472 individuals and the
      prevalence of use of at least one psychotropic medication in the three previous
      days was 6.8% (95%CI 5.5;8.1); in the adjusted analyses, there were positive
      associations between use and female sex (PR=1.48; 95%CI 1.01;2.18), worse health
      perception (PR=2.10; 95%CI 1.13;3.89), common mental disorder (PR=1.66; 95%CI
      1.09;2.51) and emotional problems (PR=8.04; 95%CI 4.87;13.02); black/brown
      skinned individuals presented significantly lower use (PR=0.58; 95%CI 0.39;0.88);
      antidepressants (52.6%), anxiolytics (28.1%) and antipsychotics (17.0%) were the
      most used. CONCLUSION: inequalities regarding sex and ethnicity/skin color were
      observed; the findings contribute to the evaluation of the rational use of these
      drugs.

PMID- 29211140
TI  - Pharmacotherapeutic profile of users and expenditure on high-cost drugs in Sao
      Leopoldo, Rio Grande do Sul State, Brazil, 2014.
AB  - OBJECTIVE: to describe the pharmacotherapeutic profile of users of the
      Specialized Program for Pharmaceutical Assistance, and to measure the expenditure
      on the most prevalent and the most expensive medications. METHODS: descriptive
      study conducted in Sao Leopoldo-RS, Brazil, with secondary data regarding
      information about requests accepted in 2014, through administrative proceedings;
      delivery notes of the State Health Department/RS were used to assess the costs.
      RESULTS: 1,528 users were included in the study, mostly women (56.7%), and the
      average age was 52 years (standard deviation=17.9); the most frequent diagnoses
      were allergic asthma (17.1%), chronic kidney disease (11.5%) and rheumatoid
      arthritis (8.4%); the most prevalent drug was budesonide+formoterol fumarate
      (18.3%); among the most prevalent drugs, the highest total monthly expense was
      with epoetin alfa (BRL37,922.34) and among the most expensive drugs, infliximab
      (BRL72,503.28). CONCLUSION: the data show the importance of the Specialized
      Program for Pharmaceutical Assistance in the high-cost treatment of highly
      prevalent.

PMID- 29211141
TI  - Hospitalizations due to drug poisoning in under-five-year-old children in Brazil,
      2003-2012.
AB  - OBJECTIVE: to describe hospitalizations due to drug poisonings in children under
      five years old, in Brazil, from 2003 to 2012. METHODS: descriptive study, with
      data from the National Hospital Information System (SIH/SUS); the drugs involved
      were divided into therapeutic classes, according to the Anatomical Therapeutic
      Chemical Classification (ATC). RESULTS: 17,725 hospitalizations were identified,
      from which 22,395 poisonings were identified, and 75 deaths; the most common
      therapeutic classes were unspecified drugs (38.0%), antiepileptic/sedative
      hypnotics/anti-parkinson drugs (19.8%), systemic antibiotics (13.4%) and non
      opioid-analgesics/antipyretics (6.5%), varying among country regions and age
      groups; in 38.5% of the poisonings it was not possible to correlate therapeutic
      classes and ATC categories. CONCLUSION: the high frequency of unspecified drugs
      was a limitation; among the specified drugs, the most common were those that act
      in the central nervous system and those used in pediatric diseases (antibiotics
      and analgesics).

PMID- 29211142
TI  - Tuberculosis in the Brazilian imprisoned population, 2007-2013.
AB  - OBJECTIVE: to describe socio-demographic and clinical characteristics and
      indicators of tuberculosis (TB) in Brazilian imprisoned population, from 2007 to
      2013. METHODS: descriptive study with data from the Information System for
      Notifiable Diseases (Sinan). RESULTS: from 2007 to 2013, 38,083 TB cases were
      reported in the imprisoned population, equivalent to a TB prevalence of 1,236
      cases/100,000 individuals; this prevalence was higher among women
      (1,693/100,000), indigenous people (2,874/100,000), and in the age group >60
      years (4,093/100,000); there were mainly reports of cases of pulmonary TB (91.5%)
      and new cases (78.1%); the TB incidence rate in 2013 (904.9/100,000) was higher
      than 2007 (627.6/100,000), whilst the mortality rate in 2013 (16.0/100,000) was
      lower than 2007 (18.0/100,000). CONCLUSION: TB in the imprisoned population
      presents some specific characteristics and higher occurrence than in the general
      population; the highest prevalence in women and the highest incidence at the end
      of the study period stood out.

PMID- 29211143
TI  - Hospitalizations due to diseases associated with poor sanitation in the public
      health care network of the metropolitan region of Porto Alegre, Rio Grande do Sul
      State, Brazil, 2010-2014.
AB  - OBJECTIVE: to describe the occurrence, characteristics and expenditures of
      hospitalizations due to diseases associated with poor sanitation funded by the
      Brazilian National Health System (SUS) among residents of the metropolitan region
      of Porto Alegre-RS, Brazil, from 2010 to 2014. METHODS: descriptive study with
      data from SUS Hospital Information System (SIH/SUS). RESULTS: out of 13,929
      hospitalizations for diseases associated with poor sanitation, 93.7% were related
      to fecal-oral transmission diseases and 20.4% were children from 1 to 4 years of
      age (28.1 hospitalizations/10,000 inhabitants/year); hospital fatality rate was
      of 2.2%, fecal-oral transmission diseases were the main causes of death;
      intensive care unit (ICU) was used in 2.0% of hospitalizations; total
      expenditures on hospitalizations was around BRL6.1 million. CONCLUSION: diseases
      associated with poor sanitation are still an important issue in the metropolitan
      region of Porto Alegre-RS, although this region presents good development
      indicators.

PMID- 29211144
TI  - Social deprivation index and leprosy in Para State, Brazil, in 2013: spatial
      analysis.
AB  - OBJECTIVE: to analyze the ecological association between the condition of social
      deprivation and leprosy detection rate in Para State, Brazil. METHODS: cross
      sectional ecological study with data from the Information System for Notifiable
      Diseases (Sinan); global and local bivariate Moran's factor analysis and
      autocorrelation were used to identify spatial patterns associated with the
      distribution of the social deprivation index (SDI) and leprosy detection rate
      (LDR). RESULTS: in 2013, 3,358 new cases of leprosy were reported in Para, with
      LDR of 41.98 cases/100,000 inhabitants; higher rates were observed in the
      municipalities of the Araguaia region; 17.5% of the 143 municipalities of the
      state were considered hyperendemic (LDR>40.00) and 30.8% presented poor SDI;
      there was spatial autocorrelation between LDR and SDI (p<0.05). CONCLUSION: there
      was spatial association between SDI and LDR, with higher leprosy detection in the
      municipalities with higher social deprivation.

PMID- 29211145
TI  - Assessment of the implementation of the Leprosy Control Program in Camaragibe,
      Pernambuco State, Brazil.
AB  - OBJECTIVE: to assess the implementation of the actions of the Leprosy Control
      Program in Camaragibe, Pernambuco State, Brazil. METHODS: evaluative research
      with 'implementation analysis', based on criteria, indicators and parameters
      guided from the construction of the Logic Model; four components were assessed -
      management, health care, epidemiological surveillance, health education and
      communication -; direct observation/questionnaire was used, as well as data from
      the Information System for Notifiable Diseases. RESULTS: the implementation of
      the program was incipient (58.3%); the estimate for the components varied from
      'not implemented' (health education and communication, 48.0%), 'incipient'
      (management, 53.3%; health care, 57.2%) to 'partially implemented'
      (epidemiological surveillance, 73.0%); in 2012, it was observed low proportion of
      examined contacts (28.4%), treatment dropout (34.1%), limited standardization of
      patient care flow, and poor resolution of problems by managers. CONCLUSION: the
      level of implementation found was related to the organization of services, with
      negative repercussions regarding the result indicators.

PMID- 29211146
TI  - Vaccination coverage according to doses received and timely administered based on
      an electronic immunization registry, Araraquara-SP, Brazil, 2012-2014.
AB  - OBJECTIVE: to describe vaccine coverage by type of vaccine at 12 and 24 months of
      age. METHODS: descriptive cohort study with children born in 2012, living in
      Araraquara-SP, Brazil, recorded in the Information System on Live Births
      (Sinasc); a manual linkage of Sinasc data with an electronic immunization
      registry (EIR) was performed; the assessment was based on vaccination status
      according to Sao Paulo State recommendations, and on doses received and timely
      administered. RESULTS: 2,740 children were registered on Sinasc and 99.6% of them
      were included into EIR; among the 2,612 (95.3%) children studied, the triple
      viral vaccine (measles, mumps and rubella) had the lowest coverage at 12 months
      for received dose (74.8%) and at 24 months for timely vaccination (53.5%) and
      received doses (88.0%). CONCLUSION: coverage was higher than 90% for most
      vaccines; however, delayed vaccination was observed, which indicates the need to
      intensify actions aimed at timely vaccination.

PMID- 29211147
TI  - Assessment of growth monitoring in child care visits at the Family Health
      Strategy in two municipalities of Paraiba State, Brazil.
AB  - OBJECTIVE: to assess the process and structural aspects of child care visits at
      the Family Health Strategy, in relation to growth monitoring. METHODS: evaluative
      study of implementation analysis, carried out in two municipalities of Paraiba
      State, Brazil; structural characteristics of the services were assessed and child
      care visits were observed for analysis of the working process. RESULTS: 119
      visits (53 in one municipality and 66 in the other) were observed; they were
      conducted by 18 nurses who were in charge of child care visits (nine from each
      municipality); five of the nurses had no training to work in primary health care
      and four units did not have a scale; weight (84.9%), height (84.0%) and cephalic
      perimeter (82.7%) measurements were held more frequently than recommendations for
      mothers (11.8% and 29.4% of the visits about height and weight, respectively).
      CONCLUSION: child growth monitoring is an action not yet consolidated, with
      significant deficiencies in the process.

PMID- 29211148
TI  - Prevalence of food intake among individuals with hypertension and diabetes in the
      municipality of Nova Boa Vista, Rio Grande do Sul, Brazil, 2013.
AB  - OBJECTIVE: to describe the food intake among individuals with high blood pressure
      and diabetes in a municipality in the south of Brazil. METHODS: a cross-sectional
      descriptive study was conducted in Nova Boa Vista-RS, Brazil, from June to
      September 2013; food intake was collected from the questionnaire of the Food and
      Nutrition Surveillance System (SISVAN) and from an adaptation based on the 2008
      Dietary Guidelines for the Brazilian Population. RESULTS: 422 individuals were
      included in the study (>=18 years old); the food that presented the highest
      recommended intake frequencies were raw salad (60.7%), fruits (73.0%), dairy
      products (61.4%), fried food (57.3%), snacks (66.4%) and soft drinks (76.3%);
      processed meat and sweets presented the highest non-recommended intake
      frequencies, with 34.8 and 23.9%, respectively. CONCLUSION: food intake among the
      population studied seems to be in accordance to the recommended frequencies,
      especially among women.

PMID- 29211149
TI  - Characteristics of the Mortality Information System in municipalities of Sao
      Paulo State, Brazil, 2015.
AB  - OBJECTIVE: to describe characteristics of the Mortality Information System (SIM)
      in municipalities of Sao Paulo State, in 2015. METHODS: descriptive study with
      data collected through an electronic questionnaire, with questions on the profile
      of technical managers, human resources and IT structure. RESULTS: 584/645
      municipalities (90.5%) participated; technical managers were mainly women
      (81.5%), nurses (64.9%), career civil servants (66.1%) and had more than 3 years
      of work experience with SIM (68.2%); in small-sized municipalities (<=30,000
      inhabitants), managers were younger (average age of 37.7 years), were also
      responsible for other systems (92.4%) and used computers with older operating
      systems (69.5%); in large-sized municipalities (>200,000 inhabitants), managers
      were older (average age of 47.1 years) and had higher education level (86.5% with
      higher education degree), they had fast-access internet (83.8%) and in-house
      technical support (81.1%). CONCLUSION: the technical managers' profile and
      availability of technological resources used at SIM were different according to
      population size of the municipalities.

PMID- 29211150
TI  - [Use of Google Maps for geocoding data from the Mortality Information System in
      Rio de Janeiro municipality, Brazil, 2010-2012].
AB  - OBJECTIVE: to describe the results of the application of a low cost procedure,
      using free software, for geocoding data from the Mortality Information System
      (SIM), in the municipality of Rio de Janeiro. METHODS: descriptive study using
      Google Maps database for geocoding deaths data recorded at SIM, occurred from
      2010 to 2012, in Rio de Janeiro; the study was carried out in three stages, (i)
      standardization of addresses, (ii) geocoding by Google Maps, and (iii) manual
      intervention. RESULTS: from the total of 26,081 addresses submitted to the
      procedure, 18,646 (71.5%) had exact matches; the remaining 7,435 were submitted
      to manual intervention, which found 5,250; 70.6% of the addresses were not
      initially found; a total of 91.6% of the addresses were geocoded. CONCLUSION: the
      procedure presented high proportion of automatic matches and, although it
      demanded much time, manual intervention allowed a considerable reduction of
      losses.

PMID- 29211151
TI  - Characteristics of suicide mortality among indigenous and non-indigenous people
      in Roraima, Brazil, 2009-2013.
AB  - OBJECTIVE: to describe suicide characteristics and mortality rates among
      indigenous and non-indigenous people in Roraima, Brazil. METHODS: descriptive
      study using data from the Mortality Information System (SIM) about the suicides
      in individuals over 10 years old, recorded in the period from 2009 to 2013;
      suicide mortality rates were adjusted by sex and age. RESULTS: 170 suicide cases
      were reported, being 17.1% among indigenous people; median ages were 24 years
      among indigenous and 29 among non-indigenous people; four municipalities
      concentrated 25/29 of the suicides among indigenous people; the 141 suicides
      among non-indigenous people were distributed in 13/15 municipalities in the
      state; suicide mortality rates were 15.0/100,000 among indigenous people and
      8.6/100,000 among non-indigenous people. CONCLUSION: ethnic-racial peculiarities
      stood out in suicide mortality; among the indigenous people, rates were higher,
      younger ages prevailed and deaths were concentrated in a smaller number of
      municipalities, when compared to non-indigenous people.

PMID- 29211152
TI  - Guidelines for reporting health economic evaluation studies.

PMID- 29211153
TI  - Enhancement of public policy with a focus on functioning: evaluations and
      reflections on the Continuous Cash Benefit program in Brazil.

PMID- 29211154
TI  - Democracy, Social Security and Income Transfer in Brazil.

PMID- 29211155
TI  - BPC: from security advances to the risk of social security reform.
AB  - This paper analyzes the proposed changes in the Continuous Cash Benefit (BPC)
      discussed within the Social Security Reform, both with regard to the Federal
      Government's original proposal in 2016 and the proposal by the rapporteur's
      project submitted to Congress in 2017. The proposed changes focus on two aspects:
      increased minimum age of access and unlinking the BPC amount from the minimum
      wage amount. The document discusses the justifications for the BPC reform,
      regarding both disincentives to social security contributions and demographic
      changes, as well as estimated possible impacts of proposed changes. The study
      concludes that measures, if approved, tend to reduce coverage and increase income
      vulnerability of the elderly and the disabled in the country.

PMID- 29211156
TI  - Street-level Bureaucracy and Social Policy in Brazil.
AB  - This paper describes the Brazilian central government bureaucracy and people with
      disabilities' access to the Continuous Cash Benefit (BPC). This access depends on
      the Ministry of Social Security bureaucracy's evaluation of the condition of
      vulnerability. We performed a literature review, analysis of secondary data from
      time series and cross-sectional data to describe street-level federal
      bureaucracy. Legal documents and indicators describe the expert evaluation
      regimen of the Ministry of Social Security (MPS). This paper shows the uneven
      growth of the number of career public servants of the central government in the
      last two decades. The Brazilian central government has adopted the international
      concept of person with disabilities in the evaluation of BPC applicants. Despite
      this decision, it is shown that the Brazilian central government expanded
      selectively the career bureaucracy to work in the social area. It was found that
      the result of the evaluation process was quite strict, favoring applicants in
      conditions of extreme biomedical vulnerability. Despite adopting the social
      model, BPC eligibility is tied to medical diagnosis.

PMID- 29211157
TI  - Social protection and public policy for vulnerable populations: an assessment of
      the Continuous Cash Benefit Program of Welfare in Brazil.
AB  - This paper describes the historical development and profile of Continuous Cash
      Benefit (BPC) applicants, intended for poor elderly and people with disabilities,
      which, since 2009, uses eligibility criteria based on the International
      Classification of Functioning, Disability and Health (ICF) of the WHO and is
      aligned with the UN Convention on the Rights of Persons with Disabilities. The
      behavior of benefits was determined from the analysis the coefficients of the
      general and non-judicial grants between 1998 and 2014. The profile was
      established for the years 2010 and 2014 according to situation of acceptance,
      age, gender and ICF components. The average annual growth of the coefficient was
      higher from 2000 to 2010, prior to the adoption of the biopsychosocial
      eligibility model, and the coefficient of non-judicial grants increased until
      2010, falling thereafter. The deferrals acceptance /rejections ratio was higher
      among children and among those facing severe or total environmental barriers,
      limitations, constraints and bodily changes. The implementation of the
      biopsychosocial evaluation model did not cause an increased rate of grants and
      results evidence the need for flexibility in the eligibility criteria.

PMID- 29211158
TI  - Continuous Cash Benefit (BCP) for disabled individuals: access barriers and
      intersectoral gaps.
AB  - The 1988 Constitution approved the Continuous Cash Benefit (BCP) directed to
      elders and disabled persons with a household per capita income of 25% of the
      minimum wage, and around 4 million people received this benefit in 2015. The
      design of BPC for disabled persons involves organizations of social security,
      social welfare and health. This paper discusses how some intersectoral
      coordination mechanisms gaps between these areas produce access barriers to
      potential beneficiaries. Results stem from a qualitative study performed with
      physicians, administrative staff and social workers from the National Institute
      of Social Security (INSS) and of the Social Welfare Reference Center (CRAS) in
      three municipalities of different Brazilian regions. Intersectoral coordination
      and cooperation are more structured at the Federal level. At the local level,
      they rely on informal and horizontal initiatives, which produce immediate but
      discontinuous solutions. The role of the CRAS remains contingent on the
      implementation. The need to establish institutionalized mechanisms for
      coordination and cooperation between social welfare, health and social insurance
      to improve the implementation and reduce barriers to access to the BCP is
      apparent.

PMID- 29211159
TI  - Social inequalities in limitations caused by chronic diseases and disabilities in
      Brazil: the 2013 National Health Survey.
AB  - This paper aims to evaluate the association between social inequalities and self
      reported limitations for the performance of daily activities caused by chronic
      diseases or disabilities. The 2013 National Health Survey evaluated a sample of
      Brazilians with 18+ years. The outcome was that individuals reported that their
      daily activities were moderately, severely or very severely limited (LIMIT) by
      one or more chronic diseases, or mental, physical, hearing or motor impairment.
      The main exposure was the economy class, classified into five categories, ranging
      from A (richest) to E (poorest). We estimated a logistic regression model
      adjusted for economy class and confounding variables, considering the complex
      sample design and alpha = 5%. Around 15.5% of individuals reported having Limit.
      Comparing social classes, 19.5%, 21.9%, 16.1%, 11.1%, and 7.7% individuals
      belonging to class E, D, C, B and A reported the outcome. The adjusted model
      showed greater odds of individuals in class D + E, and D, reporting LIMIT than
      individuals of class A + B (reference). Public policies for health care and
      social welfare for people with disabilities should focus on social classes E and
      D.

PMID- 29211160
TI  - Socioeconomic position and disability: "The Belo Horizonte, Brazil Health Study".
AB  - This study aims to investigate the association of socioeconomic status and
      comorbidities of self-reported disability. Data were obtained from a population
      survey in Belo Horizonte from 2008 to 2009. The sample was probabilistic and
      stratified by conglomerates in three stages: census tracts, households and
      individuals. The outcome variable was disability, defined by the self-reported
      problems in bodily functions or structures. The explanatory variables were
      gender, age, self-reported morbidity and socioeconomic status index that included
      variables mother and respondent schooling and household income. The factorial
      analysis was used to evaluate the socioeconomic status index and logistic
      regression. The prevalence of disability was 10.43% (95% CI: 9.1-11.7%). Self
      reported disability was associated with age (OR = 1.02; 95% CI: 1.01-1.03) and
      reporting of two or more diseases (OR = 3.24; CI 95%; 2.16-4.86) and
      socioeconomic status index (OR = 0.96; 95% CI: 0.95-0.97). The worse
      socioeconomic status and occurrence of diseases appear to contribute to the
      occurrence of disability. These results show health inequities among people with
      disabilities, and BPC relevance supporting vulnerable populations.

PMID- 29211161
TI  - Profile of demand and Continuous Cash Benefits (BCP) granted to children
      diagnosed with microcephaly in Brazil.
AB  - The Brazilian Federal Constitution of 1988 introduced the Continuous Cash
      Benefits (BCP), allowing the inclusion of people with disabilities. This is a
      descriptive study with aggregate municipal data about the time and geographic
      distribution of the incidence of microcephaly related to the Zika virus in Brazil
      and data of the BCP grants to children diagnosed with microcephaly. Data on the
      demand and BCP grants to children with microcephaly since 2009 are shown. Cases
      of microcephaly and/or central nervous system disorders were obtained from the
      Ministry of Health and totaled 2,366 confirmed cases from January 1, 2015 to
      December 31, 2016. The historical series of BCP granted from 2009 to 2016 was
      based on data from the National Institute of Social Security and showed, until
      2014, a baseline with an average of 200 annual benefits for children younger than
      48 months with microcephaly. In 2016, grants increased eight times, reaching
      1,603 benefits granted to children of 731 municipalities spread in the 27 States.
      The Northeast accounted for 73% of the BCPs granted, however, this was less than
      65% of the demand for incident cases. The implementation of the integrated
      referral system, including active search, should be strengthened to ensure access
      to all children entitled to BCP.

PMID- 29211162
TI  - Minor psychiatric disorders and their associations in family caregivers of people
      with mental disorders.
AB  - This study aims to analyze the occurrence of minor psychiatric disorder and their
      associations in relatives of people with mental disorders. This is a cross
      sectional study of 1164 relatives. For the tracking of minor psychiatric
      disorders the Self-Reporting Questionnaire Scale (SRQ20) was used, adopting 6/8
      as cut-off point. Bivariate analyzes were conducted using Chi-squared test.
      Trends among strata of independent variables were investigated in relation to the
      outcome using nonparametric linear trend test. Statistic significance was defined
      as p-value < 0.05. Crude and adjusted binary logistic regressions were conducted
      using as a basis the hierarchical model developed through a systematic literature
      review. It was observed in the population a prevalence of 46.9% for minor
      psychiatric disorders. Higher prevalence of minor psychiatric disorders were
      strongly associated with the female gender, older age, first degree family ties,
      not having a paid work, lower education level, lower income, health problems,
      lower quality of life and feeling of burden. Many factors are related to the
      emotional and mental illness of family caregivers, demanding health services to
      be prepared to recognize and intervene in these situations.

PMID- 29211163
TI  - Perception of hearing loss: use of the subjective faces scale to screen hearing
      among the elderly.
AB  - : Presbycusis is a disorder present among the elderly. However, it is under
      diagnosed, making it important to develop and enhance simple screening tools.
      OBJECTIVE: The subjective faces scale has been proposed as a method to assess
      auditory self-perception among the elderly, and its correlation with audiological
      tests. METHODS: We looked at elderly patients referred to the audiology service
      of a reference center for the care of the elderly in a public university hospital
      between February and November 2013. Patients were submitted to meatoscopy, tonal
      and vocal audiometry and the whisper test. They also answered the subjective
      faces scale. A total of 164 elderly individuals participated, and the average age
      was 77. RESULTS: We found a good correlation between the subjective faces scale
      and audiometry thresholds (r = 0.66). Our results show that the faces and hearing
      loss correlate, with face 1 corresponding to normal hearing, face 2 to mild
      hearing loss, and face 3 to Grade I moderate hearing loss. When evaluating the
      psychometric qualities of the subjective faces scale, we found that faces 2 or 3
      have good sensitivity and specificity, with the area under the ROC curve being
      0.81. CONCLUSION: The subjective faces scale seems to be a good, low-cost and
      easy to use supplementary tool for auditory screening in geriatric services.

PMID- 29211164
TI  - Screening of hearing in elderly people: assessment of accuracy and
      reproducibility of the whispered voice test.
AB  - Given the high prevalence of presbycusis and its detrimental effect on quality of
      life, screening tests can be useful tools for detecting hearing loss in primary
      care settings. This study therefore aimed to determine the accuracy and
      reproducibility of the whispered voice test as a screening method for detecting
      hearing impairment in older people. This cross-sectional study was carried out
      with 210 older adults aged between 60 and 97 years who underwent the whispered
      voice test employing ten different phrases and using audiometry as a reference
      test. Sensitivity, specificity and positive and negative predictive values were
      calculated and accuracy was measured by calculating the area under the ROC curve.
      The test was repeated on 20% of the ears by a second examiner to assess inter
      examiner reproducibility (IER). The words and phrases that showed the highest
      area under the curve (AUC) and IER values were: "shoe" (AUC = 0.918; IER =
      0.877), "window" (AUC = 0.917; IER = 0.869), "it looks like it's going to rain"
      (AUC = 0.911; IER = 0.810), and "the bus is late" (AUC = 0.900; IER = 0.810),
      demonstrating that the whispered voice test is a useful screening tool for
      detecting hearing loss among older people. It is proposed that these words and
      phrases should be incorporated into the whispered voice test protocol.

PMID- 29211165
TI  - Monitoring of hearing and language in primary health care: project pilot.
AB  - This article analyzes the feasibility of implementing a program that monitors the
      hearing and language development in the first year of life. It is a prospective
      longitudinal study, in which 41 community health workers were invited to monitor,
      on a monthly basis, by means of a questionnaire validated earlier, the hearing
      and language of children born in their micro areas of expertise. Thirty-nine
      community health workers agreed to participate, with only two refusals. Five gave
      up participating. Twenty-six (66.66%) did not perform monitoring, seven (17.94%)
      monitored improperly and only six (15.38%) monitored properly. Just one child
      failed the quiz, who was forwarded to the hospital that conducted the auditory
      screening for retesting. These professionals' high activity demand was considered
      the main reason for the difficulties encountered in this project. In addition,
      there is the difficulty to have contact with the Family Health Strategy teams, as
      well as the impossibility of permanent face-to-face discussions and the influence
      of the community health agents' supervisors.

PMID- 29211166
TI  - [Factors associated with the use of wheelchairs by institutionalized elderly
      people].
AB  - Due to the high prevalence of wheel-chair use by institutionalized elderly
      people, the scope of this research was to verify whether factors involving
      gender, age, education, length of institutionalization, comorbidities, cognition
      and functionality are associated with the use of such equipment, as well as
      ascertain the reasons for use according to the perceptions of the elderly. It is
      a cross-sectional descriptive study that included 55 elderly people subdivided
      into G1 (locomotion without assistance) and G2 (wheelchair users). Analysis of
      the profile in medical records, cognition and functionality by the Mini-Mental
      State Examination and Barthel index was conducted. Wheelchair users asked about
      the factors that lead to wheelchair use were recorded: 33 (60%) of the elderly
      were in G1 and 22 (40%) in G2. There were differences between the groups with
      respect to functionality (p = 0.005). The elderly who have not suffered a stroke
      are less likely to use a wheelchair (OR: 0.09; 95% CI: 0.02 to 0.36). Elderly
      wheelchair users reported: fear of falling, pain, tiredness, weakness in the
      legs, difficulty walking and lack of assistance in walking. Strokes and
      functionality are associated with wheelchair use. Knowledge of these factors and
      the reasons reported by the elderly may enable alternatives of prevention to be
      defined.

PMID- 29211167
TI  - [Spatial and temporal analysis of the coverage for neonatal hearing screening in
      Brazil (2008-2015)].
AB  - This article seeks to establish the coverage of neonatal hearing screening in
      Brazil between January 2008 and June 2015. It is an ecological study that uses
      the country, through the Urban Articulation Regions, as a base. To calculate the
      screening coverage percentage, the Live Births Information System, the Outpatient
      Information System and the Beneficiaries of the National Supplementary Health
      Agency Information System were used. An exploratory analysis of maps and spatial
      statistical analysis was conducted using TerraView 4.2.2 software. The coverage
      of neonatal hearing screening saw an increase of 9.3% to 37.2% during the study
      period. In 2008-2009 it was observed that the percentage of coverage ranged from
      0% to 79.92%, but most areas received coverage from 0% to 20%, though in 2014
      2015 coverage ranged from 0% to 171.77%, and there was a visible increase in the
      percentage of coverage in the country, mainly in the Southern Region. The
      screening coverage has increased over time, but is still low with an uneven
      distribution in the territory, which may be explained by local laws and policies
      and by the existence of different types of auditory health service in the
      country.

PMID- 29211168
TI  - Burden of caregivers of children and adolescents with Down Syndrome.
AB  - The aim of this study was to evaluate the profile and burden of caregivers of
      children/adolescents with and without Down syndrome. The evaluations were
      performed through questionnaires about the profile and burden of the caregivers
      (Zarit Burden Interview) and the profile of the children/adolescents. These
      questionnaires were applied to 168 caregivers. The chi-square test, Fisher's
      exact test, and analysis of variance were used with a significance level set at a
      = 5%. Both groups were composed of 84 participants, and the caregivers of the
      disabled group had a significantly higher percentage of females (p = 0.001),
      those in the 41-60 age group (p < 0.001), those who had no occupation (p <
      0.001), those with a low per capita income (p < 0.001), those with a low level of
      schooling (p = 0.021), those who were Catholic in religion (p = 0.001), those who
      had more health problems (p < 0.001), those who continued the use of medication
      (p < 0.001), and those with a moderate level of burden (p < 0.001). The
      children/adolescents with disabilities needed significantly more help for eating
      (p = 0.051), bathing (p = 0.006), dressing (p = 0.042), sphincter control (p =
      0.027), and intimate hygiene (p < 0.001). The caregivers of children/adolescents
      with Down syndrome presented a moderate burden compared to the caregivers of
      normoreactive children/adolescents.

PMID- 29211169
TI  - Artisanal fisherwomen/shellfish gatherers: analyzing the impact of upper limb
      functioning and disability on health-related quality of life.
AB  - The aim is to analyze upper limb functioning and disability, and its association
      with health-related quality of life among artisanal fisherwomen from Bahia,
      Brazil. Cross-sectional epidemiological study was conducted with a sample of 209
      fisherwomen. Structured questionnaires were used for socio-demographic and
      comorbidity information, as well as the instruments Disabilities of the Arm,
      Shoulder and Hand (DASH) and Short-Form Healthy Survey (SF-36) respectively, to
      evaluate the upper limbs and health-related quality of life. The results
      demonstrated that the presence of musculoskeletal disorders in the upper limbs
      directly affects the values of the DASH instrument and the SF-36v01 questionnaire
      scores, while also generating a negative correlation between the DASH and SF
      36v01. The varying functioning abilities, pain and social aspects negatively
      affect upper limb function, and the daily activities and work of fisherwomen. The
      presence of chronic disease and the absence of intervention and rehabilitation
      for these professionals, that could produces, in a long-term, cases of
      disability.

PMID- 29211170
TI  - [Environmental influence on physical disability: a systematic review of the
      literature].
AB  - People with physical disabilities may, in interaction with facilitators and
      barriers, modify their participation in society. The environment, in the panorama
      of the International Classification of Functioning, Disability and Health (ICF),
      plays a relevant role in health and in the expression of functioning. Thus, the
      aim of this study was to investigate the influence of environmental factors on
      physical disability, based on the theoretical framework of the ICF. A systematic
      review of the literature was performed based on the recommendations of the
      following documents: Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) and Strengthening the Reporting of Observational Studies in
      Epidemiology Statement (STROBE). The studies selected confirmed the theoretical
      precepts of the ICF. The interference of the physical and social environment, in
      general, might be attributed to different clinical conditions, especially in
      neurology, both in quantitative and qualitative studies. Methodological
      limitations were observed that may be obstacles to consolidating some guidelines,
      which should encourage further research on the subject with judicious methods,
      validated instruments and carefully selected samples.

PMID- 29211171
TI  - Nursing team, family and hospitalized child interaction: an integrative review.
AB  - This study aims to present an integrative review of national and international
      scientific papers on nursing team, family, and hospitalized child interaction.
      Searches have been made to Bireme, Lilacs, Medline, IBECS, Psyc Info, Science
      Direct and Web of Science (2008-2013) databases, which allowed us to identify 31
      papers represented by the following themes: Interpersonal relationship,
      Communication and Care. The establishment of interpersonal relationships in a
      technical and formal way causes difficulty in communication and in the actions
      aimed at providing care. Care has been the main theme in these researches.
      Companions demand increased attention to child and family needs from health
      professionals, and greater involvement of everyone in the process of care.
      Results suggest that health care teams need to recognize the dynamic experienced
      by the dyad (child/companion) in order to develop comprehensive care, encouraging
      family and child inclusion through humanization strategies.

PMID- 29211172
TI  - [The new organization of labor at public universities: collective consequences of
      job instability on the health of teachers].
AB  - The main objective of this article is to analyze the new organization of labor of
      university teachers, seeking to investigate the potential relationship with the
      health status of these workers. It is based on the assumption that job
      instability in public universities has had repercussions on the health of higher
      education teachers. A qualitative exploratory study was conducted by means of
      bibliographic research in indexed databases. As a method of analysis, thematic
      analysis was used, focusing on four empirical categories, namely: job instability
      in the teaching profession; intensification of labor; aspects of the organization
      of teaching work in universities; and data on the health of university teachers.
      It was revealed in the literature that the use of strong organizational pressures
      prevails in the university scenario and consequently the intensification of labor
      is prevalent, with emphasis on the issue of increasing the demand for academic
      productivity. It was also observed that the topic of excess workload of teachers
      is recurrent and the concept of availability of less leisure time prevails. In
      addition, the need for organized collective resistance was confirmed in order to
      modify the job instability of teaching work.

PMID- 29211173
TI  - [Josue de Castro and Brazilian social thought].
AB  - This article highlights the fact that the work of Josue de Castro brings to light
      some of the most relevant interpretations on the Brazilian food situation,
      launching the first proactive manifesto for the construction of a social policy
      on food in Brazil. Underpinning this debate, there are aspects of the process of
      construction of the Nation State, national development and the role of the
      Brazilian intellectuals. Such issues are added to the author's concern with the
      formation of proactive measures that could lead to social change and
      redefinitions of the conditions of social exclusion of a significant portion of
      the Brazilian population. We start from the assertion that his work is part of
      broader interpretations about Brazil, which need to be revisited.

PMID- 29211174
TI  - Accelerometer-determined peak cadence and weight status in children from Sao
      Caetano do Sul, Brazil.
AB  - The purpose of this study was to determine the relationship between peak cadence
      indicators and body mass index (BMI) and body fat percentage (BF%)-defined weight
      status in children. The sample comprised 485 Brazilian children. Minute-by-minute
      step data from accelerometry were rank ordered for each day to identify the peak
      1-minute, 30-minute and 60-minute cadence values. Data were described by BMI
      defined and bioelectrical impedance-determined BF% weight status. BMI-defined
      normal weight children had higher peak 1-minute (115.5 versus 110.6 and 106.6
      steps/min), 30-minute (81.0 versus 77.5 and 74.0 steps/min) and 60-minute cadence
      (67.1 versus 63.4 and 60.7 steps/min) than overweight and obese children
      (p<.0001), respectively. Defined using %BF, normal weight children had higher
      peak 1-minute (114.5 versus 106.1 steps/min), 30-minute (80.4 versus 73.1
      steps/min) and 60-minute cadence (66.5 versus 59.9 steps/min) than obese children
      (p<.0001). Similar relationships were observed in boys; however, only peak 1-
      minute cadence differed significantly across BMI and %BF-defined weight status
      categories in girls. Peak cadence indicators were negatively associated with BMI
      and BF% in these schoolchildren and significantly higher among normal weight
      compared to overweight or obese children.

PMID- 29211175
TI  - Sociodemographic, perinatal and behavioral factors associated to types of milk
      consumed by children under in six months: birth coort.
AB  - This study evaluated factors associated with the consumption of breast milk (BM),
      infant formula (IF) and cow milk (CM) in children. This was a cohort study with
      256 children followed-up at the 1st, 4th and 6th month of age in Vicosa (MG),
      Brazil. With respect to CM and IF, consumption was recorded regardless of BM
      intake. Regarding BM, only exclusive or predominant consumption was considered.
      From the 1st to the 6th month, an increase was recorded in the number of children
      who did not consume BM exclusively or predominantly (31.6%), as well as the
      consumption of CM (27.2%) and IF (9.3%). BM was associated with pacifier use at
      1st month, and mother's employment status and pacifier use in the 4th and 6th
      month. Pacifier use was a risk factor for IF consumption in every month, while
      belonging to the lower income group was inversely associated in the 6th month. As
      for CM, the number of prenatal visits was a risk factor in every month, the
      mother's employment status and use of pacifier in the 4th month, family income,
      mother's employment status, low birth weight, number of prenatal visits and
      pacifier use in the 6th month. Since the 1st month, the introduction of other
      milk types is high, revealing that there is still much to go to ensure exclusive
      breastfeeding up to 6 months.

PMID- 29211176
TI  - The relationship of climate variables in the prevalence of acute respiratory
      infection in children under two years old in Rondonopolis-MT, Brazil.
AB  - It is estimated that approximately 30% of childhood diseases can be attributed to
      environmental factors and 40% involve children under the age of five years old,
      representing about 10% of world population. This study aimed to analyze the
      relationship of climate variables in the prevalence of acute respiratory
      infection (ARI) in children under two years old, in Rondonopolis-MT, from 1999 to
      2014. It was used a cross-sectional study with a quantitative and a descriptive
      approach with meteorological teaching and research data from the database from
      the health information system. For statistical analysis, it adjusted the negative
      binomial model belonging to the class of generalized linear models, adopting a
      significance level of 5%, based on the statistical platform R. The average number
      of cases of ARI decreases at approximately by 7.9% per degree centigrade increase
      above the average air temperature and decrease about 1.65% per 1% increase over
      the average air relative humidity. Already, the rainfall not associated with
      these cases. It is the interdisciplinary team refocus practical actions to assist
      in the control and reduction of ARI significant numbers in primary health care,
      related climate issues in children.

PMID- 29211177
TI  - Individual factors associated to malocclusion in adolescents.
AB  - The study aimed to identify the severity of malocclusions and associated factors
      among Brazilian adolescents. Data from 5,445 adolescents participating in the
      Brazilian Oral Health Survey (SBBrasil 2010) were evaluated, of which 4,276 were
      included in the study based on the inclusion criteria. The dependent variable was
      severe and very severe malocclusion, according to the Dental Aesthetic Index (DAI
      > 30). The independent variables were place of residence, macro-region, self
      reported ethnicity, income, gender, schooling, access to dental care, untreated
      caries and front and back teeth loss due to caries. A hierarchical multiple
      logistical regression analysis was performed, considering the complex cluster
      sampling plan. Prevalence of severe/very severe malocclusions was 17.5%. After
      adjustments, black/brown ethnicity group (OR = 1.59, 95% CI: 1.09-2.34), lower
      household income (OR = 0.67, 95% CI: 0.55-0-82), front (OR = 2.32, 95% CI: 1.14
      4.76) and back teeth (OR = 1.45, 95% CI: 1.14-1.84) loss due to caries were
      associated with the outcome. Therefore, we conclude that black/brown ethnicity,
      lower household income and greater number of front and back teeth loss due to
      caries increased the odds for severe/very severe malocclusion.

PMID- 29211178
TI  - A wave that comes rushing in and dunks you: representations and destinies of the
      crisis in adolescent users of a CAPSi.
AB  - This article focuses on the inter-subjective aspects involved in the care of
      psychosocial crises of adolescents, their representations and developments. A
      qualitative research was developed from a psycho-sociological perspective by
      constructing life story narratives of adolescents treated at a Psychosocial Care
      Center for Children and Adolescents (CAPSi). It was based on the theoretical
      contributions of Rene Kaes on group and cultural aspects of the crisis, as well
      as its relation to adolescence. Life narratives, constructed through in-depth
      interviews with adolescents, close relatives, and CAPSi caretakers depict crisis
      as a "surprise", as violence and estrangement, an episode that must be forgotten,
      denied, silenced, and medicalized. We concluded that the crisis involves strong
      mental suffering for adolescents, for the people close to them, and for
      caretakers, which calls into question the possibilities and limits of care. We,
      therefore, highlight the importance of protected spaces in both the institution
      and the health network that would allow the collective construction of new
      meanings, representations and destinies of crisis, both by users and caretakers.

PMID- 29211179
TI  - Survival analysis of women with breast cancer: competing risk models.
AB  - This study aimed to estimate the effects of prognostic factors on breast cancer
      survival, such as age, staging, and extension of the tumor, using proportional
      hazards and competing risks models proposed by Cox and Fine-Gray, respectively.
      This is a retrospective cohort study, based on a population of 524 women, who
      were diagnosed with breast cancer in the period from 1993 to 1995 and monitored
      until 2011, residents in the city of Campinas, Sao Paulo, Brazil. The cutoff
      points for the variable of age were defined with Cox simple models. In the
      settings of simple and multiple Fine-Gray models, age was not significant to the
      presence of competing risks, neither it was in Cox models. For both models, death
      by breast cancer was the event of interest. The survival functions, estimated by
      Kaplan-Meier, showed significant differences for deaths by breast cancer and by
      competing risks. Survival functions by breast cancer did not show significant
      differences when comparing the age groups, according to log-rank test. Cox and
      Fine-Gray models identified the same prognostic factors that influenced in breast
      cancer survival.

PMID- 29211180
TI  - Factors associated with first sexual intercourse among mothers with 14-16 years
      of age from Porto Alegre/RS, Brazil.
AB  - This study analyzed the factors associated with first sexual intercourse among
      427 mothers with 14-16 years of age from Porto Alegre (RS), Brazil. Data on
      adolescent socio-demographic status (skin color, religion and schooling gap) and
      reproductive aspects (age at menarche, age at first sexual intercourse,
      partnership in first sexual intercourse and partner's age) were collected through
      household survey. Data analysis was performed using bivariate and multivariate
      analysis through Poisson regression with robust variance. Among adolescents with
      early first sexual intercourse (up to 14 years), 77.4% had menarche at up to 12
      years of age and 16.4% had casual partners in the first sexual intercourse. These
      variables were associated with the outcome and showed that early menarche
      (OR=1.26; CI 95%:1.04-1.52) and casual partner at first sexual intercourse
      (OR=1.28; CI 95%:1.09-1.49) increase by respectively 26% and 28% the prevalence
      of early first sexual intercourse. This study highlights the need to strengthen
      health programs and policies already implemented, such as the School Health
      Program, as well as reinforces that parents and teachers need to be oriented in
      an integrated manner in order to facilitate dialogue with adolescents and provide
      adequate counseling.

PMID- 29211181
TI  - [Violence committed by acquaintances - Brazil, 2013].
AB  - The scope of this article is to describe the prevalence of violence committed by
      acquaintances in accordance with demographic characteristics. It is a descriptive
      study, based on data from a population-based National Health Research survey
      conducted in Brazil in 2013. Data from the adult population (>= 18 years) of
      64,348 households. Prevalence rates were calculated and their respective 95%
      confidence intervals (95%CI) according to gender, age, education, race/color,
      area of residence and geographical region. The prevalence of violence committed
      by acquaintances was 2.5% (95%CI 2.3-2.7), significantly higher in women (3.1%;
      95%CI 2.8-3.5) compared to men (1.8%; 95% CI 1.6-2.1). This prevalence was higher
      in the population aged 18-29 years old (3.2%; 95%CI 2.8-3.7) compared to older
      individuals (1.1%; 95%CI 0.8-1.3), and among residents of the North (3.2%; 95%CI
      2.5-3.8) and Northeast Regions (3.0%; 95%CI 2.5-3.8) when compared to residents
      of the Southeast Region (2.0%; 95%CI 1.6-2.3). Violence was present in higher
      prevalence among women, proving the occurrence of gender-based violence and
      confirming its occurrence in all geographical regions and in different population
      groups in Brazil in 2013.

PMID- 29211182
TI  - [Prevalence of hemoglobin variants in quilombola communities in the state of
      Piaui, Brazil].
AB  - Hemoglobin variants (Hb) result from mutations in globin genes, with amino acid
      substitution in the polypeptide chain. Among the most common structural variants
      are HbS, HbC, HbD and HbE. The S hemoglobin gene is a high frequency gene across
      America and Brazil, where it is more frequent in the Southeast and Northeast. The
      scope of this article is to investigate the presence of hemoglobin variants in 15
      quilombos (fugitive slave communities) of Piaui. The sample was of 1,239 people
      and hemoglobin was screened by high-performance liquid chromatography (HPLC). A
      questionnaire was applied related to gender, ethnicity and consanguinity. Of the
      samples analyzed, 5.4% had AS sickle cell trait, while SS and SC sickle cell
      anemia showed a rate of 0.8%, with AC, AD and DD hemoglobin. Of the 1,069 Afro
      descendants, 84 revealed hemoglobin abnormalities, 34 being male 53 being female.
      There were 13 consanguineous marriages among the 84 hemoglobin alterations. The
      study of hemoglobin variants in 15 former quilombo communities in the state of
      Piaui contributes to their education in health in the aspects of genetic
      inheritance of hemoglobin, a relevant public health issue, providing input for
      the implementation of the State Program of Sickle Cell Disease of Piaui.

PMID- 29211183
TI  - Survival of patients with AIDS and co-infection with the tuberculosis bacillus in
      the South and Southeast regions of Brazil.
AB  - The study investigates the survival of patients with co-infection AIDS-TB through
      a retrospective study of a cohort of individuals aged 13 or more and the
      diagnosis of AIDS reported in the years 1998-99 and following 10 years. Of the
      2,091 AIDS cases, 517 (24.7%) had positive diagnosis for tuberculosis, and 379
      (73.3%) were male. The risk among co-infected patients was 1,65 times the not co
      infected. Have been compared the exposed and non-exposed through the Kaplan-Meier
      and Cox method. The variables associated with longer survival were: female gender
      (HR = 0.63), educational level >= eight years (HR = 0.52), CD4 diagnostic
      criteria (HR = 0.64); and shorter survival: age >= 60 years (HR = 2.33), no use
      of HAART (HR = 8.62), no investigation to Hepatitis B (HR = 2.44) and
      opportunistic infections >= two (HR = 1.97). The average survival rate, related
      to TB infection was 69 months for the Southeast region and 73 months for the
      South. AIDS and tuberculosis require monitoring and treatment adherence and they
      are markers of the quality of care and survival of patients in Brazil.

PMID- 29211184
TI  - Participatory environmental diagnosis and of health risks from the surrounding
      communities the Petrochemical Complex of Rio de Janeiro, Brazil.
AB  - The aim of this study was to diagnose the priority socio environmental problems
      and the health risks from the surrounding communities the Petrochemical Complex
      of Rio de Janeiro. Characterized by a participatory approach, the action research
      has led to the application of interviews, focal groups, meetings and workshop
      with social actors of Porto das Caixas and Sambaetiba districts, located in
      Itaborai city/RJ from November 2013 to December 2014. A structural analysis of
      the problems prioritized by the communities (water supply, sewage treatment and
      risk of transmissible diseases; risk of air pollution and respiratory diseases;
      absence of public security and risk of violence) sketched out the cause-effect
      intervention relationship, on the basis of the Protocol for Assessing Community
      Excellence in Environmental Health. The process revealed the absence of
      representativity of the social actors of the studied localities in spaces of
      decision-making on the environmental issue. Educational actions with
      professionals and inhabitants that aim to promote the formation of collective
      movements urge, indispensable to guarantee the rights of mitigation of situations
      of contamination of air and access to sanitation services and public security and
      thus of conditions of lower risk to health.

PMID- 29211185
TI  - What every intensivist should know about using high-flow nasal oxygen for
      critically ill patients.

PMID- 29211186
TI  - Epidemiology of acute kidney injury and chronic kidney disease in the intensive
      care unit.
AB  - OBJECTIVE: To describe the epidemiology of acute kidney injury, its relationship
      to chronic kidney disease, and the factors associated with its incidence.
      METHODS: A cohort study and follow-up were conducted in an intensive care unit in
      Montevideo, Uruguay. We included patients admitted between November 2014 and
      October 2015 who were older than 15 years of age and who had at least two
      measurements of serum creatinine. We excluded patients who were hospitalized for
      less than 48 hours, patients who died at the time of hospitalization, and
      patients with chronic renal disease who were on hemodialysis or peritoneal
      dialysis. There were no interventions. Acute kidney injury was defined according
      to the criteria set forth in Acute Kidney Injury Disease: Improving Global
      Outcomes, and chronic kidney disease was defined according to the Chronic Kidney
      Disease Work Group. RESULTS: We included 401 patients, 56.6% male, median age of
      68 years (interquartile range (IQR) 51-79 years). The diagnosis at admission was
      severe sepsis 36.3%, neurocritical 16.3%, polytrauma 15.2%, and other 32.2%. The
      incidence of acute kidney injury was 50.1%, and 14.1% of the patients suffered
      from chronic kidney disease. The incidence of acute septic kidney injury was
      75.3%. Mortality in patients with or without acute kidney injury was 41.8% and
      14%, respectively (p < 0.001). In the multivariate analysis, the most significant
      variables for acute kidney injury were chronic kidney disease (odds ratio (OR)
      5.39, 95%CI 2.04 - 14.29, p = 0.001), shock (OR 3.94, 95%CI 1.72 - 9.07, p =
      0.001), and severe sepsis (OR 7.79, 95%CI 2.02 - 29.97, p = 0.003). CONCLUSION:
      The incidence of acute kidney injury is high mainly in septic patients. Chronic
      kidney disease was independently associated with the development of acute kidney
      injury.

PMID- 29211187
TI  - The Epimed Monitor ICU Database(r): a cloud-based national registry for adult
      intensive care unit patients in Brazil.
AB  - OBJECTIVE: To describe the Epimed Monitor Database(r), a Brazilian intensive care
      unit quality improvement database. METHODS: We described the Epimed Monitor(r)
      Database, including its structure and core data. We presented aggregated
      informative data from intensive care unit admissions from 2010 to 2016 using
      descriptive statistics. We also described the expansion and growth of the
      database along with the geographical distribution of participating units in
      Brazil. RESULTS: The core data from the database includes demographic,
      administrative and physiological parameters, as well as specific report forms
      used to gather detailed data regarding the use of intensive care unit resources,
      infectious episodes, adverse events and checklists for adherence to best clinical
      practices. As of the end of 2016, 598 adult intensive care units in 318 hospitals
      totaling 8,160 intensive care unit beds were participating in the database. Most
      units were located at private hospitals in the southeastern region of the
      country. The number of yearly admissions rose during this period and included a
      predominance of medical admissions. The proportion of admissions due to
      cardiovascular disease declined, while admissions due to sepsis or infections
      became more common. Illness severity (Simplified Acute Physiology Score - SAPS 3 
      62 points), patient age (mean = 62 years) and hospital mortality (approximately
      17%) remained reasonably stable during this time period. CONCLUSION: A large
      private database of critically ill patients is feasible and may provide relevant
      nationwide epidemiological data for quality improvement and benchmarking purposes
      among the participating intensive care units. This database is useful not only
      for administrative reasons but also for the improvement of daily care by
      facilitating the adoption of best practices and use for clinical research.

PMID- 29211188
TI  - Neurally adjusted ventilatory assist in pediatrics: why, when, and how?

PMID- 29211189
TI  - Intraoperative protective mechanical ventilation: what is new?

PMID- 29211190
TI  - Incidence and risk factors for surgical site infection in general surgeries.
AB  - OBJECTIVE: to estimate the incidence of surgical site infection in general
      surgeries at a large Brazilian hospital while identifying risk factors and
      prevalent microorganisms. METHOD: non-concurrent cohort study with 16,882
      information of patients undergoing general surgery from 2008 to 2011. Data were
      analyzed by descriptive, bivariate and multivariate analysis. RESULTS: the
      incidence of surgical site infection was 3.4%. The risk factors associated with
      surgical site infection were: length of preoperative hospital stay more than 24
      hours; duration of surgery in hours; wound class clean-contaminated, contaminated
      and dirty/infected; and ASA index classified into ASA II, III and IV/V.
      Staphyloccocus aureus and Escherichia coli were identified. CONCLUSION: the
      incidence was lower than that found in the national studies on general surgeries.
      These risk factors corroborate those presented by the National Nosocomial
      Infection Surveillance System Risk Index, by the addition of the length of
      preoperative hospital stay. The identification of the actual incidence of
      surgical site infection in general surgeries and associated risk factors may
      support the actions of the health team in order to minimize the complications
      caused by surgical site infection.

PMID- 29211191
TI  - Changing the mind: hypnosis and diabetes.

PMID- 29211193
TI  - Work process of nursing professors.
AB  - OBJECTIVE: to analyze the work process of nursing professors. METHOD:
      descriptive, exploratory and qualitative study, developed with a focus on
      critical epidemiology, carried out at a School of Nursing in Chile. The research
      subjects consist of 17 nursing professors, with whom individual semi-structured
      interviews were carried out and nine participated in a focus group. The Ethics
      Committee approved this study. RESULTS: 88.2% were female, mean age of 42 years,
      47% were married, 94% were Chilean, average length of service in the institution
      of 2.8 years, and 23.5% had a master's degree. Regarding the work process, the
      students were the work object, the tools used were the knowledge and the
      experience as a nurse, and the work environment was considered good. Regarding
      the form of work organization, 76% have a 44-hour workweek, the wage was
      considered inadequate and the workload was higher than foreseen in the contract.
      The dialectic of the nursing work process is evidenced, demonstrating the
      contradiction between the low wages and labor overload and the narratives
      reporting a good work environment, personal fulfillment and transcendence that
      goes far beyond work. CONCLUSIONS: the work process allows describing the work
      components of the nursing professors, which are consistent with the results of
      the literature and show the dialectic of the nursing work process.

PMID- 29211192
TI  - Tobacco addiction in the psychiatric population and in the general population.
AB  - OBJECTIVE: To estimate the degree of tobacco addiction and identify independently
      associated factors by comparing the psychiatric population of secondary and
      tertiary care with the general population of the primary healthcare network.
      METHOD: This is a cross-sectional epidemiological study, conducted in a
      municipality of Sao Paulo, with 134 smokers of a Mental Health Outpatient Unit
      (MHOU), a Psychiatric Hospital (PH), and a Primary Healthcare Unit (PHU). Data
      were collected by means of individual interviews, recorded on a mobile device.
      Data were statistically processed using Stata/12. RESULTS: Of the 134
      participants, 54.5% were women. While 49.1% of the psychiatric population
      (MHOU/PH) had medium/high nicotine addiction, 58.3% of smokers of the general
      population had very low/low dependency. The Poisson regression model indicated a
      higher prevalence of smokers with high dependence among men (PR = 1.41), people
      aged 49 years or less (15 - 29 years, PR = 4.06, 30 - 39 PR = 2.96 years, 40 - 49
      years PR = 1.84), with severe mental disorders (PR = 3.05), with anxiety
      disorders/other (PR = 3.98), and with high suicide risk (PR = 1.55). CONCLUSION:
      Nicotine dependence was greater in the psychiatric population than in the general
      population. The independent factors associated with severe dependence were sex,
      age group, diagnosis, and current risk of suicide. These results trigger
      reflection among nurses on the need to focus more attention on a neglected
      subject in mental health services.

PMID- 29211194
TI  - Telephone interventions in adherence to receiving the Pap test report: a
      randomized clinical trial.
AB  - OBJECTIVE: to test the efficacy of the behavioral and educational interventions
      undertaken by telephone, for women's attendance at the consultation to receive
      the Pap test report. METHOD: a randomized clinical trial, with a sample
      randomized in three groups: telephone call - educational (n=171), telephone call 
      reminder (n=171) and comparison (n=169). The inclusion criteria were to be of
      legal age, to have become sexually active, to undertake the preventive
      examination during the study and to have a mobile or fixed telephone. The
      educational group received a telephone call involving a script based in the
      motivational interview and in the Brazilian guidelines. The behavioral group
      received a telephone call involving a reminder about the consultation. The
      comparison group received a card with details of when to return for a
      consultation regarding the results. RESULTS: the women who received one of the
      interventions had a non-return rate of 7.3% and an increase of 39% (RR CI95%:
      1.24-1.55) in the protection against this outcome. In the individual analysis of
      the interventions, it was evidenced that both are efficacious, as the telephone
      call - reminder reduces the woman's failure to return to the service by 40% (RR
      CI95%: 1.25-1.57), while the telephone call - educational does so by 37% (RR
      CI95%: 1.22-1.54). The rates of non-return were of 6.5% and 8.2%, respectively,
      as against 33.1% in the comparison group. CONCLUSION: the interventions tested
      showed greater efficacy in the educational and behavioral contexts, in relation
      to the normal attendance, as they motivated the women to return to the service to
      receive the Pap test report. Clinical trial register: RBR-w3vnc.

PMID- 29211195
TI  - Impact of two bundles on central catheter-related bloodstream infection in
      critically ill patients.
AB  - OBJECTIVE: To evaluate the impact of the implementation of insertion and
      maintenance bundles on the rates of catheter-related bloodstream infection in an
      intensive care unit. METHOD: This is a quasi-experimental, before-and-after study
      with a non-equivalent control group. During a six-month period, insertion and
      maintenance bundles for the central venous catheters were implemented.
      Supervision guidelines were developed to assess compliance with the bundle and
      catheter characteristics. RESULTS: A total of 444 central catheters corresponding
      to 390 patients were observed, of which 68.7% were inserted in the unit. The
      maintenance and insertion bundles reached 62.9% and 94.7% compliance,
      respectively, and 50.7% of the insertions were supervised. It was possible to
      observe a 54.5% decrease in the rate of central catheter infection (3.48 vs 1.52
      x 1000 days/catheter, p<0.05) when compared with the control group. CONCLUSION:
      The simultaneous implementation of insertion and maintenance bundles has a
      positive impact on the reduction of catheter-related bloodstream infection;
      therefore it is an efficient alternative to improve the quality and safety of
      care in high complexity units.

PMID- 29211196
TI  - Analysis of ineffective breathing pattern and impaired spontaneous ventilation of
      adults with oxygen therapy.
AB  - OBJECTIVE: to analyze the manifestation of the defining characteristics of the
      nursing diagnoses of ineffective breathing pattern and impaired spontaneous
      ventilation, of the NANDA International and the defining characteristics
      identified in the literature for the concept of "ventilation" in adult patients
      hospitalized in an intensive care unit with use of oxygen therapy. METHOD:
      clinical diagnostic validation study, conducted with 626 patients in intensive
      care using oxygen therapy, in three different modalities. Multiple correspondence
      analysis was used to verify the discriminative capacity of the defining
      characteristics and latent class analysis to determine the diagnostic accuracy of
      them, based on the severity level defined by the ventilatory mode used. RESULTS:
      in the multiple correspondence analysis, it was demonstrated that the majority of
      the defining characteristics presented low discriminative capacity and low
      percentage of explained variance for the two dimensions (diagnoses). Latent class
      models, separately adjusted for the two diagnoses, presented a worse fit, with
      sharing of some defining characteristics. Models adjusted by level of severity
      (ventilation mode) presented better fit and structure of the component defining
      characteristics. CONCLUSION: clinical evidence obtained in the present study
      seems to demonstrate that the set of defining characteristics of the two nursing
      diagnoses studied fit better in a single construct.

PMID- 29211197
TI  - Development and validation of an algorithm for laser application in wound
      treatment.
AB  - OBJECTIVE: To develop and validate an algorithm for laser wound therapy. METHOD:
      Methodological study and literature review. For the development of the algorithm,
      a review was performed in the Health Sciences databases of the past ten years.
      The algorithm evaluation was performed by 24 participants, nurses,
      physiotherapists, and physicians. For data analysis, the Cronbach's alpha
      coefficient and the chi-square test for independence was used. The level of
      significance of the statistical test was established at 5% (p<0.05). RESULTS: The
      professionals' responses regarding the facility to read the algorithm indicated:
      41.70%, great; 41.70%, good; 16.70%, regular. With regard the algorithm being
      sufficient for supporting decisions related to wound evaluation and wound
      cleaning, 87.5% said yes to both questions. Regarding the participants' opinion
      that the algorithm contained enough information to support their decision
      regarding the choice of laser parameters, 91.7% said yes. The questionnaire
      presented reliability using the Cronbach's alpha coefficient test (alpha =
      0.962). CONCLUSION: The developed and validated algorithm showed reliability for
      evaluation, wound cleaning, and use of laser therapy in wounds.

PMID- 29211198
TI  - Respiratory status of adult patients in the postoperative period of thoracic or
      upper abdominal surgeries.
AB  - OBJECTIVE: to evaluate the respiratory status of postoperative adult patients by
      assessing the nursing outcome Respiratory Status. METHOD: descriptive, cross
      sectional study developed with 312 patients. Eighteen NOC indicators were
      assessed and rated using a Likert-scale questionnaire and definitions.
      Descriptive and correlative analysis were conducted. RESULTS: the most
      compromised clinical indicators were coughing (65.5%), auscultated breath sounds
      (55%), and respiratory rate (51.3%). Factors associated with worse NOC ratings in
      specific clinical indicators were sex, age, pain, and general anesthesia.
      CONCLUSIONS: certain clinical indicators of respiratory status were more
      compromised than others in postoperative patients. Patient and context-related
      variables can affect the level of respiratory compromise.

PMID- 29211199
TI  - Why is quaternary prevention important in prevention?
AB  - Quaternary prevention consists in the identification of persons at risk of
      excessive medicalization and their protection against new unnecessary
      interventions, avoiding iatrogenic damages. Here, we argue about the importance
      of quaternary prevention in specific primary and secondary prevention. The recent
      great development of preventive medicine, biomedicalization of risks and their
      treatment as if they were diseases, and the powerful influence of the commercial
      interests of pharmaceutical industries on the production of medical-sanitary
      knowledge alter classifications, create diseases and pre-diseases, lower cutoff
      points, and erase the distinction between prevention and healing. This situation
      converts larger amounts of asymptomatic persons into sick individuals and diverts
      clinical attention and resources from sick persons to the healthy, from older
      adults to young persons, and from the poor to the rich. Quaternary prevention
      facilitates and induces the development and systematization of operational
      knowledge and guidelines to contain hypermedicalization and the damages of
      preventive actions in professional care, especially in primary health care.

PMID- 29211200
TI  - Air pollution and hospitalizations in the largest Brazilian metropolis.
AB  - OBJECTIVE: To evaluate the impact of air pollution on hospitalizations for
      respiratory and cardiovascular diseases in the largest Brazilian metropolis.
      METHODS: This study was carried out at the Metropolitan Region of Sao Paulo,
      Brazil. Environmental data were obtained from the network of monitoring stations
      of nine municipalities. Air pollution exposure was measured by daily means of
      PM10 (particles with a nominal mean aerodynamic diameter <= 10 MUm) per
      municipality, while daily counts of hospitalizations for respiratory and
      cardiovascular diseases within the Brazilian Unified Health System were the
      outcome. For each municipality a time series analysis was carried out in which a
      semiparametric Poisson regression model was the framework to explain the daily
      fluctuations on counts of hospitalizations over time. The results were combined
      in a meta-analysis to estimate the overall risk of PM10 in hospitalizations for
      respiratory and cardiovascular diseases at the Metropolitan Region of Sao Paulo.
      RESULTS: Regarding hospitalizations for respiratory diseases, the effect
      estimates were statistically significant (p < 0.05) for all municipalities,
      except Santo Andre and Taboao da Serra. The RR (Relative Risk) of this outcome
      for an increase of 10 ug/m3 in the levels of PM10 ranged from 1.011 (95%CI 1.009
      1.013) for Sao Paulo to 1.032 (95%CI 1.024-1.040) in Sao Bernardo do Campo. The
      RR of hospitalization for respiratory diseases in children for an increase of 10
      ug/m3 of PM10 ranged from 1.009 (95%CI 1.001-1.017) in Santo Andre to 1.077
      (95%CI 1.056-1.098) in Maua. Only Sao Paulo and Sao Bernardo do Campo presented
      positive and statistically significant results for hospitalizations for
      cardiovascular diseases. CONCLUSIONS: This is the first study to estimate the
      risk of illness from air pollution in the set of municipalities of the
      Metropolitan Region of Sao Paulo, Brazil. Global estimates of the effect of
      exposure to pollution in the region indicated associations only with respiratory
      diseases. Only Sao Paulo and Sao Bernardo do Campo showed an association between
      the levels of PM10 and hospitalizations for cardiovascular diseases.

PMID- 29211201
TI  - Use of linkage to improve the completeness of the SIM and SINASC in the Brazilian
      capitals.
AB  - OBJECTIVE: To analyze the contribution of linkage between databases of live
      births and infant mortality to improve the completeness of the variables common
      to the Mortality Information System (SIM) and the Live Birth Information System
      (SINASC) in Brazilian capitals in 2012. METHODS: We studied 9,001 deaths of
      children under one year registered in the SIM in 2012 and 1,424,691 live births
      present in the SINASC in 2011 and 2012. The databases were related with linkage
      in two steps - deterministic and probabilistic. We calculated the percentage of
      incompleteness of the variables common to the SIM and SINASC before and after
      using the technique. RESULTS: We could relate 90.8% of the deaths to their
      respective declarations of live birth, most of them paired deterministically. We
      found a higher percentage of pairs in Porto Alegre, Curitiba, and Campo Grande.
      In the capitals of the North region, the average of pairs was 84.2%; in the South
      region, this result reached 97.9%. The 11 variables common to the SIM and SINASC
      had 11,278 incomplete fields cumulatively, and we could recover 91.4% of the data
      after linkage. Before linkage, five variables presented excellent completeness in
      the SINASC in all Brazilian capitals, but only one variable had the same status
      in the SIM. After applying this technique, all 11 variables of the SINASC became
      excellent, while this occurred in seven variables of the SIM. The city of birth
      was significantly associated with the death component in the quality of the
      information. CONCLUSIONS: Despite advances in the coverage and quality of the SIM
      and SINASC, problems in the completeness of the variables can still be
      identified, especially in the SIM. In this perspective, linkage can be used to
      qualify important information for the analysis of infant mortality.

PMID- 29211202
TI  - Uncited articles in Brazilian public health journals.
AB  - Here, we describe the percentage of non-citation in Brazilian public health
      journals, a field that, until now, had not been investigated nationally or
      internationally. We analyzed articles, published between 2008 and 2012, of eight
      public health journals indexed in the scopus database. The percentage of non
      citation differs between journals (from 5.7% to 58.1%). We identified four
      statistically distinct groups: Historia, Ciencia, Saude - Manguinhos (58% uncited
      articles); Physis: Revista de Saude Coletiva, Interface, and Saude e Sociedade
      (32% to 37%); Ciencia & Saude Coletiva and Revista Brasileira de Epidemiologia
      (16% to 17%); and Cadernos de Saude Publica and Revista de Saude Publica (6%).
      The non-citation in the first three years post-publication also varies according
      to journal. Four journals have shown a clear decline of non-citation: Cadernos de
      Saude Publica, Ciencia & Saude Coletiva, Revista Brasileira de Epidemiologia, and
      Physis. Another three (Revista de Saude Publica, Saude e Sociedade, and
      Interface) presented an oscillation in non-citation, but the rates of 2008 and
      2012 are similar, with different magnitudes. In turn, the journal Historia,
      Ciencia, Saude - Manguinhos maintains high rates of non-citation.
      Multidisciplinary journals attract more citation, but a comprehensive citation
      model still needs to be formulated and tested.

PMID- 29211203
TI  - Risk factors for caries-free time: longitudinal study in early childhood.
AB  - OBJECTIVE: To estimate time in days from the beginning of follow-up up to the
      development of dental caries in children under 30 months and to assess risk
      factors potentially affecting the development of the disease. METHODS: The study
      population of the cohort study were children attending public, private, and
      charitable day care centers in Salvador, Northeastern Brazil, followed up for
      fourteen months. We used the multivariate Cox regression to estimate risk and
      Kaplan-Meier method to estimate the caries-free time. RESULTS: Of the 495
      children studied, 112 developed caries (22.6%). Mean caries-free time was 248.6
      (SD = 96.2) days. The comparasion of curves by age group (> 24 months) and
      children attending public day care showed more caries in a shorter period (p <
      0.00). The following variables were important risk factors for increased rate of
      caries: district of origin (HR = 1.88, 95%CI 1.27-2.77), category of day care (HR
      = 3.88, 95%CI 2.04-7.38), age (HR = 1.77, 95%CI 1.15-2.74), bottle-feeding before
      sleep time after the age of 12 months (HR = 1.62, 95%CI 1.04-2.51), presence of
      active white spots (HR = 2.70, 95%CI 1.07-6.80), and living in non-masonry house
      (HR = 1.68, 95%CI 1.02-2.76). The highest hazard ratio (HR = 4.60, 95%CI 2.80
      7.42) was found for previous caries experience. CONCLUSIONS: Social variables
      were considered as of high risk for the development of dental caries.

PMID- 29211204
TI  - Pragmatic criteria of the definition of neonatal near miss: a comparative study.
AB  - OBJECTIVE: The objective of this study was to test the validity of the pragmatic
      criteria of the definitions of neonatal near miss, extending them throughout the
      infant period, and to estimate the indicators of perinatal care in public
      maternity hospitals. METHODS: A cohort of live births from six maternity
      hospitals in the municipalities of Sao Paulo, Niteroi, and Rio de Janeiro,
      Brazil, was carried out in 2011. We carried out interviews and checked prenatal
      cards and medical records. We compared the pragmatic criteria (birth weight,
      gestational age, and 5' Apgar score) of the definitions of near miss of Pileggi
      et al., Pileggi-Castro et al., Souza et al., and Silva et al. We calculated
      sensitivity, specificity (gold standard: infant mortality), percentage of deaths
      among newborns with life-threatening conditions, and rates of near miss,
      mortality, and severe outcomes per 1,000 live births. RESULTS: A total 7,315
      newborns were analyzed (completeness of information > 99%). The sensitivity of
      the definition of Pileggi-Castro et al. was higher, resulting in a higher number
      of cases of near miss, Souza et al. presented lower value, and Pileggi et al. and
      de Silva et al. presented intermediate values. There is an increase in
      sensitivity when the period goes from 0-6 to 0-27 days, and there is a decrease
      when it goes to 0-364 days. Specificities were high (>= 97%) and above
      sensitivities (54% to 77%). One maternity hospital in Sao Paulo and one in
      Niteroi presented, respectively, the lowest and highest rates of infant
      mortality, near miss, and frequency of births with life-threatening conditions,
      regardless of the definition. CONCLUSIONS: The definitions of near miss based
      exclusively on pragmatic criteria are valid and can be used for monitoring
      purposes. Based on the perinatal literature, the cutoff points adopted by Silva
      et al. were more appropriate. Periodic studies could apply a more complete
      definition, incorporating clinical, laboratory, and management criteria,
      including congenital anomalies predictive of infant mortality.

PMID- 29211205
TI  - Validity of self-reported weight, height, and BMI in mothers of the research
      Birth in Brazil.
AB  - OBJECTIVE: To evaluate the accuracy of information on pre-gestational weight,
      height, pre-gestational body mass index, and weight at the last prenatal
      appointment, according to maternal characteristics and sociodemographic and
      prenatal variables. METHODS: The study was developed using data from the face-to
      face questionnaire and prenatal card (gold standard) of the study "Birth in
      Brazil, 2011-2012". To evaluate the differences between the measured and self
      reported anthropometric variables, we used the the Kruskal-Wallis test for the
      variables divided into quartiles. For the continuous variables, we used the
      Wilcoxon test, Bland-Altman plot, and average difference between the information
      measured and reported by the women. We estimated sensitivity and the intraclass
      correlation coefficient. RESULTS: In the study, 17,093 women had the prenatal
      card. There was an underestimation of pre-gestational weight of 1.51 kg (SD =
      3.44) and body mass index of 0.79 kg/m2 (SD = 1.72) and overestimation of height
      of 0.75 cm (SD = 3.03) and weight at the last appointment of 0.22 kg (SD = 2.09).
      The intraclass correlation coefficients (ICC) obtained for the anthropometric
      variables were: height (ICC = 0.89), pre-gestational weight (ICC = 0.96), pre
      gestational body mass index (ICC = 0.92), and weight at the last appointment (ICC
      = 0.98). CONCLUSIONS: The results suggest that the mentioned anthropometric
      variables were valid for the study population, and they may be used in studies of
      populations with similar characteristics.

PMID- 29211206
TI  - Inequality of opportunity in health: evidence from Chile.
AB  - OBJECTIVE: To assess the possible presence of inequality of opportunities in the
      health status of Chileans, according to sociodemographic circumstances. METHODS:
      Self-rated health data were used from the Chilean National Health Survey of 2010
      to test the hypothesis of strong and weak equality of opportunities in the health
      status of the Chilean population. These hypotheses were tested using
      nonparametric techniques and second-order stochastic dominance criteria. RESULTS:
      Robust empirical evidence was obtained, which indicate that the education level
      of the mother, household socioeconomic status, sex, zone, and region of residence
      determine opportunities to achieve good health in Chile. CONCLUSIONS: Better
      health status was identified for Chilean adults whenever their mothers had a
      higher education level, their household income was higher, they were men, or
      lived in urban areas. The region of residence also affects opportunities to
      achieve good health in Chile.

PMID- 29211207
TI  - Cardiovascular secondary prevention in primary care setting: an immediate
      necessity in Brazil and worldwide.

PMID- 29211208
TI  - Accuracy of spirometry for detection of asthma: a cross-sectional study.
AB  - BACKGROUND: Asthma is a chronic inflammatory disease with airway
      hyperresponsiveness. Spirometry is the most commonly used test among asthmatic
      patients. Another functional test used for diagnosing asthma is the bronchial
      challenge test. The aim of this study was to analyze the accuracy of spirometry
      for detecting asthma in the general population. DESIGN AND SETTING: Cross
      sectional study with data analysis to evaluate the accuracy of spirometry through
      calculating sensitivity, specificity and predictive values and through the kappa
      agreement test. METHODS: Subjects who constituted a birth cohort were enrolled at
      the age of 23 to 25 years. Spirometric abnormality was defined as reduced forced
      expiratory volume in one second, i.e. lower than 80% of the predicted value.
      Measurement of bronchial responsiveness was performed by means of the bronchial
      challenge test with methacholine. The gold-standard diagnosis of asthma was
      defined as the presence of bronchial hyperresponsiveness in association with
      respiratory symptoms. RESULTS: Asthma was detected in 200 subjects (10.4%) out of
      the sample of 1922 individuals. Spirometric abnormality was detected in 208
      subjects (10.9%) of the sample. The specificity of spirometric abnormality for
      detecting asthma was 90%, sensitivity was 23%, positive predictive value was 22%,
      and negative predictive value was 91%. The kappa test revealed weak agreement of
      0.13 (95% confidence interval, CI: 0.07-0.19) between spirometry and the
      diagnosis of asthma. CONCLUSION: Spirometry, as a single test, has limitations
      for detecting asthma in the general population.

PMID- 29211209
TI  - Risk and protection factors for self-reported hypertension and diabetes in Joao
      Pessoa, Brazil. The VIGITEL survey, 2014. A cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: Chronic diseases are the main cause of death among adults
      and are responsible for most outpatient and hospital care expenses in Brazil. The
      objective here was to determine the prevalence of hypertension and diabetes and
      to analyze the associations with risk and protection factors among adults. DESIGN
      AND LOCAL: Cross-sectional study in a state capital in northeastern Brazil.
      METHODS: Data on adults of both sexes aged >= 45 years who were interviewed in
      the Vigitel telephone survey in 2014 were analyzed. Prevalence ratios were
      estimated using Poisson regression, to identify associated factors. RESULTS:
      Among women, the prevalence of hypertension was 48.4% and of diabetes, 12.7%;
      among men, the prevalences were 41.9% and 13.8%, respectively. Multivariate
      analysis showed that for women, age group >= 65 years, overweight, self-assessed
      poor health and dyslipidemia remained associated with higher prevalence of
      hypertension. For men, overweight and self-assessed poor health remained
      associated with higher prevalence of hypertension. Regarding diabetes, in the
      multivariate model for women, age group 55-64 years, schooling level between zero
      and four years and no regular consumption of beans remained associated with
      higher prevalence. For men, age groups 55-64 years and >= 65 years and being
      married or in a stable partnership were associated with higher prevalence of
      diabetes. CONCLUSIONS: The results indicated that the prevalences of hypertension
      and diabetes were high and that preventable factors were associated with this
      situation, thus providing support for public policies aimed towards coping with
      this.

PMID- 29211210
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.1590/1516-3180.2017.0023190317].

PMID- 29211211
TI  - The Emblematic Year of 2011, Trials and the 50 Years of Heart Transplantation:
      Three Relevant Issues.

PMID- 29211212
TI  - Comparative Study of Electrical Stimulation of the Heart with VDD and DDD
      Pacemakers as to the Evolution to Atrial Fibrillation.
AB  - INTRODUCTION: The pacemaker implantation VDD is considered simpler, faster, less
      expensive and causes fewer complications compared to DDD. However, the VDD
      pacemaker has not been widely used in many centers, perhaps for fear of
      dysfunction of the sinus node and the reduction of atrial sensitivity by the
      pacemaker during follow-up after implantation. OBJECTIVE: To compare patients
      with DDD and VDD pacemakers regarding the evolution of chronic atrial
      fibrillation (AF) and length of stay outside this postoperative arrhythmia.
      METHODS: It was included 158 patients with dual chamber pacemakers, 48 DDD and
      110 VDD. Follow-up period: between January 1, 1999 and December 31, 2015. The
      mean follow-up of patients with DDD was 5.35 years and the VDD, 4.74 years. The
      percentage of each group (DDD and VDD) which evolved to AF during follow-up was
      assessed. Also, it was made an actuarial study with the respective curves
      indicating the time free from AF for each group. Patients were classified
      according to the diagnosis that led to pacemaker implantation and the degree of
      heart failure. RESULTS: The percentage of patients who developed AF was higher in
      DDD group (10.42%) than in VDD group (6.36%), but without statistical
      significance. Patients with DDD and VDD remained free of AF for similar period.
      CONCLUSION: Considering the results, the VDD pacemaker continues to be a good
      option to the DDD for routine use in cases properly indicated.

PMID- 29211213
TI  - Hybrid Treatment with Complete Transposition of Supra-Aortic Trunks versus
      Conventional Surgery for the Treatment of Aortic Arch Aneurysm.
AB  - OBJECTIVE: The disease of the aortic arch is traditionally approached by open
      surgical repair requiring cardiopulmonary bypass and circulatory arrest. This
      study performed a retrospective analysis comparing outcomes through primary
      hybrid patients submitted to aortic arch surgery without cardiopulmonary bypass
      with patients submitted to conventional open surgery. METHODS: 25 patients
      submitted to the aortic arch surgery were selected in the period 2003-2012 at the
      Madre Teresa Hospital in the city of Belo Horizonte, Brazil; 13 of these
      underwent hybrid technique without cardiopulmonary bypass and 12 underwent
      conventional open surgery. RESULTS: The mortality rate for the hybrid group was
      23% and for the conventional surgery group was 17% (P=0.248). The postoperative
      complication rate was also similar in both groups, with no significant
      difference. CONCLUSION: Both techniques proved to be similar in mortality and
      morbidity. However, due to the small sample, more analytical studies with larger
      samples and long-term follow-up are needed to clarify this issue.

PMID- 29211214
TI  - Hybrid Approach of Aortic Diseases: Zone 1 Delivery and Volumetric Analysis on
      the Descending Aorta.
AB  - INTRODUCTION: Conventional techniques of surgical correction of arch and
      descending aortic diseases remains as high-risk procedures. Endovascular
      treatments of abdominal and descending thoracic aorta have lower surgical risk.
      Evolution of both techniques - open debranching of the arch and endovascular
      approach of the descending aorta - may extend a less invasive endovascular
      treatment for a more extensive disease with necessity of proximal landing zone in
      the arch. OBJECTIVE: To evaluate descending thoracic aortic remodeling by means
      of volumetric analysis after hybrid approach of aortic arch debranching and
      stenting the descending aorta. METHODS: Retrospective review of seven consecutive
      patients treated between September 2014 and August 2016 for diseases of proximal
      descending aorta (aneurysms and dissections) by hybrid approach to deliver the
      endograft at zone 1. Computed tomography angiography were analyzed using a
      specific software to calculate descending thoracic aorta volumes pre- and
      postoperatively. RESULTS: Follow-up was done in 100% of patients with a median
      time of 321 days (range, 41-625 days). No deaths or permanent neurological
      complications were observed. There were no endoleaks or stent migrations. Freedom
      from reintervention was 100% at 300 days and 66% at 600 days. Median volume
      reduction was of 45.5 cm3, representing a median volume shrinkage by 9.3%.
      CONCLUSION: Hybrid approach of arch and descending thoracic aorta diseases is
      feasible and leads to a favorable aortic remodeling with significant volume
      reduction.

PMID- 29211215
TI  - Predictive Factors of Long-Term Stay in the ICU after Cardiac Surgery: Logistic
      CASUS Score, Serum Bilirubin Dosage and Extracorporeal Circulation Time.
AB  - OBJECTIVE: To test the capacity of the Logistic CASUS Score on the second
      postoperative day, the total serum bilirubin dosage on the second postoperative
      day and the extracorporeal circulation time, as possible predictive factors of
      long-term stay in Intensive Care Unit after cardiac surgery. METHODS: Eight-two
      patients submitted to cardiac surgery with extracorporeal circulation were
      selected. The Logistic CASUS Score on the second postoperative day was calculated
      and bilirubin dosage on the second postoperative day was measured. The
      extracorporeal circulation time was also registered. Patients were divided into
      two groups: Group A, those who were discharged up to the second day of
      postoperative care; Group B, those who were discharged after the second day of
      postoperative care. RESULTS: In this study, 40 cases were listed in Group A and
      42 cases in Group B. The mean extracorporeal circulation time was 83.9+/-29.4 min
      in Group A and 95.8+/-29.31 min in Group B. Extracorporeal circulation time was
      not significant in this study (P=0.0735). The level of P significance of
      bilirubin dosage on the second postoperative day was 0.0003 and an area under the
      ROC curve of 0.708 with a cut-off point at 0.51 mg/dl was registered. The level
      of P significance of Logistic CASUS Score on the second postoperative day was
      0.0001 and an area under the ROC curve of 0.723 with a cut-off point at 0.40% was
      registered. CONCLUSION: The Logistic CASUS Score on the second postoperative day
      has shown to be better than the bilirubin dosage on the second postoperative day
      as a predictive tool for calculating the length of stay in intensive care unit
      during the postoperative care period of patients. Notwithstanding, extracorporeal
      circulation time has failed to prove itself as an efficient tool to predict an
      extended length of stay in intensive care unit.

PMID- 29211217
TI  - Application of Unilateral Pectoralis Major Muscle Flap in the Treatment of
      Sternal Wound Dehiscence.
AB  - OBJECTIVE: This study aims to report the use of the unilateral pectoralis major
      muscle flap for the treatment of the sternal wound dehiscence. METHODS: A
      retrospective study including patients who underwent unilateral pectoralis major
      muscle flap was performed for the treatment of sternotomy dehiscence due to
      coronary artery bypass, valve replacement, congenital heart disease correction
      and mediastinitis, between 1997 and 2016. Data from the epidemiological profile
      of patients, length of hospital stay, postoperative complications and mortality
      rate were obtained. RESULTS: During this period, 11 patients had their dehiscence
      of sternotomy treated by unilateral pectoralis major muscle flap. The patients
      had a mean age of 54.7 years, the mean hospital stay after flap reconstruction
      was 17.9 days (from 7 to 52 days). In two patients, it was necessary to harvest a
      flap from the rectus abdominis fascia, in association with the pectoralis major
      muscle flap, to facilitate the closure of the distal wound. In the postoperative
      period, seroma discharge from the surgical wound was observed in six patients,
      five reported intense pain (temporary), three had partial cutaneous dehiscence,
      and two presented granuloma of the incision. CONCLUSION: The complex wound from
      sternotomy dehiscences presents itself as a challenge to surgical teams.
      Treatment should include debridement of necrotic tissue and preferably coverage
      with well-vascularized tissue. We propose that the unilateral pectoralis major
      muscle flap is an interesting and low morbidity option for the reconstruction of
      sternal wound dehiscences, with proper sternum stability and satisfactory
      functional and aesthetic outcomes.

PMID- 29211216
TI  - Cardiac Surgery in Jehovah's Witness Patients: Experience of a Brazilian Tertiary
      Hospital.
AB  - INTRODUCTION: The outcomes of Jehovah's Witness (JW) patients submitted to open
      heart surgery may vary across countries and communities. The aim of this study
      was to describe the morbidity and mortality of JW patients undergoing cardiac
      surgery in a tertiary hospital center in Southern Brazil. METHODS: A case-control
      study was conducted including all JW patients submitted to cardiac surgery from
      2008 to 2016. Three consecutive surgical non-JW controls were matched to each
      selected JW patient. The preoperative risk of death was estimated through the
      mean EuroSCORE II. RESULTS: We studied 16 JW patients with a mean age of 60.6+/
      12.1 years. The non-JW group included 48 patients with a mean age of 63.3+/-11.1
      years (P=0.416). Isolated coronary artery bypass graft surgery was the most
      frequent surgery performed in both groups. Median EuroSCORE II was 1.29 (IQR:
      0.66-3.08) and 1.43 (IQR: 0.72-2.63), respectively (P=0.988). The mortality
      tended to be higher in JW patients (18.8% vs. 4.2%, P=0.095), and there was a
      higher difference between the predicted and observed mortality in JW patients
      compared with controls (4.1 and 18.8% vs. 2.1 and 4.2%). More JW patients needed
      hemodialysis in the postoperative period (20.0 vs. 2.1%, P=0.039). CONCLUSION: We
      showed a high rate of in-hospital mortality in JW patients submitted to cardiac
      surgery. The EuroSCORE II may underestimate the surgical risk in these patients.

PMID- 29211218
TI  - Impact of Myocardial Revascularization Method on Smoking Cessation: Coronary
      Artery Bypass Grafting versus Percutaneous Coronary Intervention.
AB  - INTRODUCTION: Smoking is a serious public health issue, being a precursor of
      heart disease and a predictor of sudden death due to myocardial ischemia. Major
      events in the patient's health can lead to radical changes in habits and the
      choice for different myocardial revascularization methods might differently
      impact smoking cessation and relapse. OBJECTIVE: To study the rate and
      perpetuation of smoking cessation after myocardial revascularization comparing
      coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      (PCI). METHODS: Smokers submitted to myocardial revascularization were divided
      into CABG and PCI groups. The research was conducted through interviews at the
      Hospital Santa Lucinda outpatient clinic. Patients with smoking cessation longer
      than 90 days before hospital admission, combined procedures, hospital readmission
      before 360 days after discharge, cases of death at any time, and emergency
      procedures were excluded from the study. The start of the smoking cessation
      period was determined as just after hospital discharge, with a follow-up of 12
      months. RESULTS: The proportion of patients reporting smoking relapse was
      significantly lower in the CABG than in the PCI group at 30 (11.1% vs. 20.8%;
      P=0.039) and at 180 days (23.1% vs. 41.5%; P=0.002), but no differences were
      observed between the two groups at 360 days after hospital discharge (51.9% vs.
      54.1%; P=0.719). High levels of nicotine dependence and passive smoking showed to
      be important predictors of smoking relapse in the long-term. CONCLUSION: The
      occurrence of a major surgical procedure seems to have beneficial psychological
      effects, representing an interesting setting for smoking cessation counseling to
      have higher chances of success.

PMID- 29211219
TI  - Incidence and Treatment of Chylothorax in Children Undergoing Corrective Surgery
      for Congenital Heart Diseases.
AB  - INTRODUCTION: Chylothorax is a lymphatic extravasation into pleural cavity and
      its incidence is 0.25%-5.3% in children undergoing cardiac surgery. OBJECTIVE: To
      evaluate the incidence of chylothorax in pediatrics patients operated, linking it
      in each surgical intervention. Evaluate treatment types and efficiency. METHODS:
      Retrospective study using medical records of children undergoing cardiac surgery
      in the Hospital do Coracao between 2004 and 2014. For statistical analysis,
      qualitative variables by absolute frequency and relative frequency; quantitative
      variables, by median of 25 and 75 percentiles, as they did not present normal
      distribution (Shapiro-Wilk, P<0.05). The Chi-square test was used for the
      association between type of treatment and result. The adopted confidence level
      was 95%. RESULTS: Incidence of chylothorax was 2.1% (0.9% in intracardiac
      surgery, 1.7% correction of patent ductus arteriosus and aortic coarctation, 8.3%
      Glenn's surgery, 11.8% total cavopulmonary surgery and 3% in others). Among
      treatments, fasting associated with total parenteral nutrition (TPN) resolved 51%
      of the cases. Hypoglossal diet had failed treatment and surgical referral in 22%
      of the cases. Fasting with TPN associated with octreotide had success in the
      treatment of chylothorax in a period exceeding 15 days in 78% of cases, and 3.7%
      were referred for surgery. CONCLUSION: According to the results, incidence of
      chylothorax was 2.18%. Treatment with fasting and TPN leads to resolutions in
      86.5%, and the association with octreotide was successful in 85.1% of cases,
      showing an efficient option, while the treatment with hypoglossal diet had
      therapeutic failure in 22% of the cases in which it was used.

PMID- 29211220
TI  - Blood Transfusion and Increased Perioperative Risk in Coronary Artery Bypass
      Grafts.
AB  - OBJECTIVE: To correlate blood transfusions and clinical outcomes during
      hospitalization in coronary artery bypass grafting surgery (CABG). METHODS:
      Transfusion, clinical and hematological data were collected for 1,378 patients
      undergoing isolated or combined CABG between January 2011 and December 2012. The
      effect of blood transfusions was evaluated through multivariate analysis to
      predict three co-primary outcomes: composite ischemic events, composite
      infectious complications and hospital mortality. Because higher risk patients
      receive more transfusions, the hospital mortality outcome was also tested on a
      stratum of low-risk patients to isolate the effect of preoperative risk on the
      results. RESULTS: The transfusion rate was 63.9%. The use of blood products was
      associated with a higher incidence of the three coprimary outcomes: composite
      infectious complications (OR 2.67, 95% CI 1.70 to 4.19; P<0.001), composite
      ischemic events (OR 2.42, 95% CI 1.70 to 3.46; P<0.001) and hospital mortality
      (OR 3.07, 95% CI 1.53 to 6.13; P<0.001). When only patients with logistic
      EuroSCORE <= 2% were evaluated, i.e., low-risk individuals, the mortality rate
      and the incidence of ischemic events and infectious complications composites
      remained higher among the transfused patients [6% vs. 0.4% (P<0.001), 11.7% vs.
      24,3% (P<0.001) and 6.5% vs. 12.7% (P=0.002), respectively]. CONCLUSION: The use
      of blood components in patients undergoing CABG was associated with ischemic
      events, infectious complications and hospital mortality, even in low-risk
      patients.

PMID- 29211221
TI  - Safety and Feasibility Study of a Novel Stent-Graft for Thoracic Endovascular
      Aortic Repair: a Canine Model Experiment.
AB  - OBJECTIVE: To evaluate the safety and feasibility of a novel stent-graft for
      thoracic endovascular aortic repair (TEVAR) in a canine model, 9 adult hybrid
      dogs were used for the experiment. METHODS: All animals were implanted with a
      novel thoracic aortic stent-graft via femoral artery. Blood sample was collected
      at pre-operation and 1, 2, 4, 8 and 12 weeks after implantation for hematological
      examination. Moreover, tissues from randomly selected 4 dogs were subjected to
      histopathological analysis with the optical microscope after stent-grafts were
      implanted for 3, 6, 9, and 12 months respectively. The experimental period lasted
      for more than 2 years. RESULTS: A total of 9 stent-grafts were successfully
      implanted in the canine thoracic aortas and no migration or deformation occurred.
      Related indicators of blood routine, inflammatory factors, and immunology changes
      were not significantly (P>0.05), except the white blood cell (WBC) counts in the
      first week. Moreover, abnormal morphology was not found in all thoracic aortas
      via histopathological examination. Additionally, all stent-grafts were patent and
      did not migrate, and there was no thrombus in the lumens of stent-grafts.
      CONCLUSION: The novel thoracic aortic stent-graft made in China was safe and
      feasible for thoracic endovascular aortic repair in a canine model.

PMID- 29211222
TI  - CABG Surgery Remains the best Option for Patients with Left Main Coronary Disease
      in Comparison with PCI-DES: Meta-Analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: To compare the safety and efficacy of coronary artery bypass grafting
      (CABG) with percutaneous coronary intervention (PCI) using drug-eluting stents
      (DES) in patients with unprotected left main coronary artery (ULMCA) disease.
      METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and
      reference lists of relevant articles were searched for clinical studies that
      reported outcomes at 1-year follow-up after PCI with DES and CABG for the
      treatment of ULMCA stenosis. Five studies fulfilled our eligibility criteria and
      they included a total of 4.595 patients (2.298 for CABG and 2.297 for PCI with
      DES). RESULTS: At 1-year follow-up, there was no significant difference between
      CABG and DES groups concerning the risk for death (risk ratio [RR] 0.973,
      P=0.830), myocardial infarction (RR 0.694, P=0.148), stroke (RR 1.224, P=0.598),
      and major adverse cerebrovascular and cardiovascular events (RR 0.948, P=0.680).
      The risk for target vessel revascularization (TVR) was significantly lower in the
      CABG group compared to the DES group (RR 0.583, P<0.001). It was observed no
      publication bias regarding the outcomes, but only the outcome TVR was free from
      substantial statistical heterogeneity of the effects. In the meta-regression,
      there was evidence that the factor "female gender" modulated the effect regarding
      myocardial infarction rates, favoring the CABG strategy. CONCLUSION: CABG surgery
      remains the best option of treatment for patients with ULMCA disease, with lower
      TVR rates.

PMID- 29211224
TI  - History of Heart Transplantation: a Hard and Glorious Journey.

PMID- 29211223
TI  - Effectiveness of Implantation of Cardioverter-Defibrillators Therapy in Patients
      with Non-Ischemic Heart Failure: an Updated Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Implantable cardioverter-defibrillator has become the first-line
      therapy for prevention of sudden cardiac death. Controversial results still exist
      regarding the effectiveness of implantable cardioverter-defibrillator (ICD) in
      non-ischemic heart failure. METHODS: The PubMed, Embase, and Cochrane Central
      databases were searched for randomized trials comparing implantable cardioverter
      defibrillator in combination with medical treatment versus medical treatment for
      non-ischemic heart failure. The primary endpoint was incidence of all-cause
      death. We derived pooled risk ratios with fixed-effects models. RESULTS: Five
      studies enrolling 2573 patients were included. Compared with medical treatment,
      implantable cardioverter-defibrillator with medical treatment was associated with
      a significantly lower risk for all-cause mortality (Risk ratio: 0.83; 95%
      confidence interval 0.71 to 0.97). CONCLUSION: Compared with medical treatment
      only, implantable cardioverter-defibrillator in combination with medical
      treatment reduces all-cause mortality.

PMID- 29211226
TI  - Implantation of Short-Term and Long-Term Right Ventricular Assist Devices.
AB  - The last decade has seen considerable growth in the use of left ventricular
      assist devices (LVAD), in end-phase heart failure treatment. The indications,
      contraindications and implantation techniques are well-defined. However,
      information about mechanical support for right ventricular failure is lacking.
      The aim of this communication is to present alternative techniques for
      implantation of short- and longterm right ventricular assist devices. Implanting
      the device in the right atrium has certain advantages when compared with the
      right ventricle. It is an easier surgical technique that preserves the tricuspid
      valve and it can potentially reduce the risk of pump thrombosis.

PMID- 29211225
TI  - Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study
      Protocol for the FRAGILE Multicenter Randomized Controlled Trial.
AB  - INTRODUCTION: Advances in modern medicine have led to people living longer and
      healthier lives. Frailty is an emerging concept in medicine yet to be explored as
      a risk factor in cardiac surgery. When it comes to CABG surgery, randomized
      controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY),
      elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients.
      Therefore, we believe that off-pump CABG could be an important technique in
      patients with limited functional capacity to respond to surgical stress. In this
      study, the authors introduce the new national, multicenter, randomized,
      controlled trial "FRAGILE", to be developed in the main cardiac surgery centers
      of Brazil, to clarify the potential benefit of off-pump CABG in frail patients.
      METHODS: FRAGILE is a two-arm, parallel-group, multicentre, individually
      randomized (1:1) controlled trial which will enroll 630 patients with blinded
      outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which
      aims to compare adverse cardiac and cerebrovascular events after off-pump versus
      on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause
      mortality, acute myocardial infarction, cardiac arrest with successful
      resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and
      coronary reintervention. Secondary outcomes will be major adverse cardiac and
      cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic
      shock, new onset of atrial fibrillation, renal replacement therapy, reoperation
      for bleeding, pneumonia, length of stay in intensive care unit, length of stay in
      hospital, number of units of blood transfused, graft patency, rate of complete
      revascularization, neurobehavioral outcomes after cardiac surgery, quality of
      life after cardiac surgery and costs. DISCUSSION: FRAGILE trial will determine
      whether off-pump CABG is superior to conventional on-pump CABG in the surgical
      treatment of pre-frail and frail patients. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated
      on March 21st 2016.

PMID- 29211227
TI  - Resection of Left Atrial Myxoma in a Patient with Retrosternal Gastric Tube: a
      Case Report.
AB  - The median sternotomy remains the standard approach in cardiovascular surgery
      but, in some conditions, it can be considered difficult to perform, especially in
      patients with history of esophagectomy. This case report describes a successful
      resection of a left atrial myxoma through a right anterolateral thoracotomy
      approach in a patient with a previous retrosternal gastric tube reconstruction.
      The decision for the best surgical approach was made after a heart surgery team
      discussion. Through this surgical access, a safe and excellent exposure of the
      left atrium was possible, and a complete resection of the myxoma was performed
      without any injury to the gastric tube.

PMID- 29211228
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.21470/1678-9741-2017-0053].

PMID- 29211229
TI  - Brazilian Congress of Cardiovascular Surgery.

PMID- 29211230
TI  - Psychic and moral exhaustion in primary care workers.
AB  - OBJECTIVE To report the experience of developing a workshop proposal to assist
      local managers with the identification, management and prevention of primary care
      workers' psychic and moral exhaustion. METHOD The workshop was developed through
      a literature review performed between November 2014 and June 2015. The temporal
      cut considered studies of the ten previous years. The selection included studies
      describing collective interventions for situations generating psychic and moral
      exhaustion, preferably in primary care services. RESULTS Thirty-five articles
      were analyzed. The workshop provides five meetings with an average duration of
      one hour. The themes are: awareness; recognizing personal stress; dealing with
      personal stress; recognizing team stress; and dealing with team stress. The
      workshop is based on five key principles: detection and coping; attention to
      interpersonal relationships; communication; self-knowledge and mindfulness.
      CONCLUSION Psychic and moral exhaustion may reflect negatively on workers'
      health, the care, and the organization. The proposal of measures to recognize,
      deal with and prevent psychic and moral exhaustion is relevant and strategic in
      the constant search for improvement of satisfaction and quality.

PMID- 29211231
TI  - Intimate partner violence among health professionals: distribution by autonomous
      communities in Spain.
AB  - OBJECTIVE To determine the prevalence of intimate partner violence among health
      care professionals who work in the Spanish National Health System, according to
      the autonomous communities of Spain. METHOD This was a descriptive cross
      sectional multicenter study conducted with male and female health professionals
      (doctors, nurses, and nursing aides) in the different autonomous communities that
      are part of the Spanish National Health System. The following instruments were
      employed: among women, an intimate partner violence screening questionnaire; and
      among men, a questionnaire that screened for violence in the family environment.
      RESULTS A total of 1,039 health professionals participated in the study. Of
      these, 26% had suffered some type of abuse. Among the men, this prevalence was
      2.7%, while among the women, it was 33.8%. There were differences in the
      prevalence of intimate partner violence among different autonomous communities,
      with the highest percentages in the Canary Islands. In terms of profession, 19.5%
      of the doctors had been exposed to intimate partner violence, while this
      percentage was 31% and 48.6% for nurses and nursing professionals, respectively.
      CONCLUSION The results indicate the presence of intimate partner violence among
      healthcare personnel in most of the autonomous communities of Spain. The data
      demonstrate the need to implement action plans, both to support victims and to
      mitigate the problem.

PMID- 29211232
TI  - Association between workload of the nursing staff and patient safety outcomes.
AB  - OBJECTIVE To describe the workload of the nursing team and relate it with patient
      safety outcomes in clinical and surgical inpatient units of a university
      hospital. METHOD Cross-sectional study, carried out from October 2013 to
      September 2015. The factor under study was the workload, expressed as the ratio
      between the mean number of patients and the number of nursing professionals in 24
      hours and in the day shifts. RESULTS The sample consisted of 157,481 patients,
      502 nursing professionals and 264 observations of safety outcomes. The ratios of
      patients per nurse and per nursing technician in day shifts indicate a mean
      estimate of 14-15 and 5-6 patients per professional, respectively. There was a
      significant association between the workloads in the inpatient units and average
      length of stay, urinary infection related to invasive procedure and the
      satisfaction of patients with nursing care. CONCLUSION The increase in the
      workload of the nursing team had an impact on quality of care and safety for
      patients. An adequate staffing promotes a safer care environment.

PMID- 29211233
TI  - Elderly caregivers living in urban, rural and high social vulnerability contexts.
AB  - OBJECTIVE Comparing the differences in the sociodemographic, care and health
      profiles of elderly caregivers of the elderly living in urban, rural, and high
      social vulnerability contexts. METHOD A cross-sectional study developed with
      elderly caregivers enrolled in the Family Health Units of a municipality in the
      interior of Sao Paulo. Household interviews and evaluations were conducted on:
      Activities of Daily Living (ADL), self-reported pain, frailty, cognition, life
      satisfaction, family functionality, burden, stress and hope. RESULTS A total of
      343 elderly caregivers of elderly individuals participated in the study, of which
      55.1% lived in an urban context, 23.6% in rural areas, and 21.3% in a context of
      high social vulnerability. The majority of elderly caregivers were women across
      the three contexts, with a median age of 67 years and caring for their spouse.
      Caregivers from regions of high social vulnerability had lower education level,
      received less emotional and material help to care, were less satisfied with life,
      more fragile, in more cognitive decline, had worse family functionality and a
      lower level of hope when compared to caregivers of urban and rural contexts
      (p<=0.05). However, caregivers from areas of high vulnerability were more
      independent for ADL. CONCLUSION Professionals working in Primary Care should
      consider these differences when planning interventions aimed at the specific
      group of caregivers.

PMID- 29211234
TI  - Comparison of the cognitive performance of elderly caregivers with and without
      chronic pain.
AB  - OBJECTIVE Understanding and characterizing chronic pain in elderly caregivers,
      verifying the cognitive performance of the elderly of the sample and verifying
      whether there is difference in the cognitive performance of elderly caregivers
      with and without chronic pain. METHOD Participants were people aged 60 years or
      older who lived with another elderly person in the same household and who were
      registered in Family Health Units. Data collection took place at participants'
      homes. Pain was assessed by the EMADOR and cognition was assessed by ACE-R.
      Statistical analyzes were performed using Shapiro-Wilk's and Mann-Whitney U
      tests. RESULTS The study included 187 elderly caregivers with chronic pain and
      133 without chronic pain, with a higher frequency of women. Chronic pain was
      present in 58.4% of the participants. Regarding the sociodemographic variables,
      there was no difference between the groups except for the gender variable
      (p=0.025). No difference was found in cognitive performance among the elderly
      with chronic pain and those without chronic pain for any domain of the ACE-R
      instrument. CONCLUSION The results contradicted the initial hypothesis that there
      would be a difference between the groups; however, there is a gap in the
      scientific knowledge on chronic pain and cognition, especially in elderly
      caregivers, opening perspectives for future investigations.

PMID- 29211235
TI  - Adolescent health promotion and the School Health Program: complexity in the
      articulation of health and education.
AB  - Objective To analyze the context of health promotion with adolescents in the
      health and education interface focusing on the actions of the Brazilian School
      Health Program. Qualitative study conducted in 2015 with professionals working in
      the Regional Executive Coordination IV, in Fortaleza, Ceara. The data obtained in
      the interview were processed in the ALCESTE program. 17 health professionals and
      22 education professionals participated in the study. The organization of
      spontaneous demand causes disharmony in the scheduled visits and health actions
      in the school. The difficulties in the implementation of the School Health
      Program were demonstrated by the lack of knowledge, the lack of planning among
      the sectors and the different demarcations in the territory. The professionals'
      lack of knowledge regarding the program and the lack of action planning confirm
      the disarticulation of the education and health sectors, although they indicate
      the possibilities of this inter-sectoral practice.

PMID- 29211236
TI  - Effects of sacred music on the spiritual well-being of bereaved relatives: a
      randomized clinical trial.
AB  - OBJECTIVE To evaluate the effects of instrumental sacred music and sacred music
      with vocals on the spiritual well-being of bereaved relatives. METHOD This is a
      randomized clinical trial carried out with family members bereaving the death of
      loved ones to cancer. Participants were allocated into three groups: Group 1
      (control), Group 2 (experimental using sacred music with vocals) or Group 3
      (experimental using instrumental sacred music). Spiritual well-being was assessed
      through the Spiritual Well-Being Scale. RESULTS Sixty-nine (69) family members
      participated. Mean scores before and after the intervention indicated high levels
      of spiritual well-being (106.4 and 105.5 in Group 1; 103.2 and 105.2 in Group 2;
      107.4 and 108.7 in Group 3) and religious well-being (57.9 and 56.9 in Group 1;
      56.3 and 56.4 in Group 2; 57.4 and 58.1 in Group 3), and moderate levels of
      existential well-being (48.5 and 48.6 in Group 1; 46.9 and 48.9 in Group 2; 49.9
      and 50.7 in Group 3), with the exception of Group 3 which presented a high level
      of existential well-being after the intervention. CONCLUSION The results show
      that there were no statistically significant differences in the spiritual well
      being scores between the experimental groups and the control group. We evidence
      the need for further studies that use music therapy as a Nursing intervention for
      bereaved families. Brazilian Registry of Clinical Trials: RBR-2wtwjz.

PMID- 29211237
TI  - Embracement as an analyzer of the relationships between professionals, managers
      and users.
AB  - OBJECTIVE Analyzing the relationships among professionals and between
      professionals with managers and users based on the user embracement analyzer.
      METHOD A qualitative study incorporating the theoretical-methodological reference
      of institutional analysis. The data were produced through focus groups and
      organized from transcription, transposition and reconstitution. Seventeen (17)
      focus group sessions were conducted involving six municipalities and health
      professionals from various backgrounds. RESULTS 137 professionals participated in
      this study. User embracement has been carried out with the aim to organize
      spontaneous demand. Doctors have not been directly involved, although they have
      the final say. Intermediate nursing deals with the users and nurses perform
      important negotiation work among the network sectors. The receptionists and the
      community agents develop the first approach to the users, forwarding them to
      nursing to negotiate the service. Managers hope to avoid complaints by attending
      everyone. Users take advantage of party politics and of the media for services
      when there is no access. CONCLUSION User embracement is an analyzer, since it
      produces visibility and readability of the relations being produced in health
      services, and when analyzed can lead to denaturalizing these actions.

PMID- 29211238
TI  - Bibliometric indicators of the nursing journals according to the index databases.
AB  - Objective To analyze the bibliometric indicators of the national and
      international journals in the area of nursing from the perspective of index
      databases. Method A historical cohort referring to the period of 2014 to 2016.
      National nursing journals indexed in the SciELO database and classified in the
      Qualis as A1, A2 and B1, and international nursing journals with impact factor
      above 1.0 and below 1.8, indexed in the Web of Science and Scopus Bases, were
      selected. Nursing specialty periodicals were excluded. The bibliometric
      indicators were collected from the index databases and imported into Ms Excel for
      analysis and data tabulation. Results The bibliometric indicators of the
      different index databases are divergent and cannot be compared. Lower title
      coverage and shorter calculation periods amplify the distortions between the
      indicators of national and international journals. Conclusion The
      internationalization criteria imposed on national journals do not contribute to
      obtaining or increasing the impact factor. A broader coverage of indexed titles
      and a longer calculation period for citations represent a significant difference
      in results. The h-index and CiteScore appear to be better impact indicators for
      national nursing research.

PMID- 29211239
TI  - Urban malaria transmission in a non-endemic area in the Andean region of
      Colombia.
AB  - BACKGROUND: Rapid urbanisation in difficult socio-economic conditions such as
      inadequate housing infrastructure, lack of public services, improper sanitation,
      and poor water drainage systems in vegetation-rich areas lead to ecological
      conditions that are conducive to the breeding of mosquitoes and transmission of
      malaria, in semi-urban and urban settings. OBJECTIVES: This study aimed to
      describe the cases of malaria that were reported in the peri-urban areas of
      Pereira (Colombia), between 2008 and 2015. METHODS: A retrospective study was
      conducted using data from the Malaria Surveillance System 2009-2015 and an
      outbreak study (between December 2008 and March 2009). Frequency distributions
      and summary measures, as well as univariate analysis were performed for all the
      variables in consideration. The annual parasite index (API) was calculated.
      FINDINGS: Data on 214 cases were obtained from the surveillance system. A
      majority of the cases were reported in men (63.1%), followed by in children < 15
      years (23.8%), and were caused predominantly by Plasmodium vivax (86.0%), with
      most of the infection occurring in the urban areas (52.8%) of Pereira. The API,
      by sex and age group, was higher among men >= 80 years. The outbreak study
      reported 14 cases of malaria in rural/peri-urban neighborhoods, and it was
      observed that the anopheline breeding sites were in close proximity to the houses
      in these areas. This population did not use protective measures against
      mosquitoes and chemical control was conducted through residual and spatial
      insecticide spraying. MAIN CONCLUSIONS: This study suggested the presence of
      autochthonous malaria transmission, in Pereira, between 2008 and 2015, most of
      which were cases of P. vivax. A greater intensity was observed between 2008 and
      2009 when malaria was possibly reintroduced to the region. During the years of
      the study, a gradual decrease in the number of reported cases of malaria was
      observed in Pereira, except for the time period between 2008 and 2009 when a
      spike was noted (estimated using the API); this was most likely caused by an
      outbreak. Interventions that are more aggressive in nature are required to
      prevent further malarial transmission and dissemination.

PMID- 29211240
TI  - Natural environmental water sources in endemic regions of northeastern Brazil are
      potential reservoirs of viable Mycobacterium leprae.
AB  - BACKGROUND: The detection of live Mycobacterium leprae in soil and animals other
      than humans suggests that the environment plays a role in the transmission of
      leprosy. OBJECTIVE: The objective of this study was to investigate the presence
      of viable M. leprae in natural water sources used by the local population in five
      municipalities in the state of Ceara, northeastern Brazil. METHODS: Samples were
      collected from 30 different sources. Viable bacilli were identified by reverse
      transcriptase polymerase chain reaction (PCR) of the M. leprae gyrA gene and
      sequencing of the PCR products. Physicochemical properties of each water source
      were also assessed. FINDINGS: M. leprae gyrA mRNA was found in 23 (76.7%) of the
      water sources. No association was found between depth of the water and sample
      positivity, nor was there any association between the type of water used by the
      population and sample positivity. An association between viable M. leprae and
      temperature and pH was found. Georeferencing showed a relation between the
      residences of leprosy cases and water source containing the bacterium. MAIN
      CONCLUSIONS: The finding of viable M. leprae in natural water sources associated
      with human contact suggests that the environment plays an important role in
      maintaining endemic leprosy in the study region.

PMID- 29211241
TI  - Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat
      labile enterotoxin.
AB  - BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a
      potent mucosal immune adjuvant. However, there is little information about LTB's
      potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better
      understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat
      of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral
      immune response induced by this construct and comparing it to that generated when
      aluminium hydroxide is used as adjuvant instead. METHODS: BALB/c mice were
      immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto
      aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1,
      IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The
      ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2
      immune response. FINDINGS: Western blot confirmed rR1, either alone or fused to
      LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its
      activity when expressed in a heterologous system. Mice immunised with the rLTBR1
      fusion protein produced approximately twice as much anti-rR1 immunoglobulins as
      mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated
      with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed
      Th1/Th2 immune response. We speculate this might be a result of rR1 immune
      modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced
      approximately 1.5-fold more serum IgA than animals immunised with rR1 and
      aluminium hydroxide. MAIN CONCLUSIONS: The results suggest that rLTB is a more
      powerful parenteral adjuvant than aluminium hydroxide when administered
      intraperitoneally as it induced higher antibody titres. Therefore, we recommend
      that rLTB be considered an alternative adjuvant, even if different administration
      routes are employed.

PMID- 29211242
TI  - Potentially pathogenic Acanthamoeba genotype T4 isolated from dental units and
      emergency combination showers.
AB  - BACKGROUND: Acanthamoeba is the genus of free-living amoebae that is most
      frequently isolated in nature. To date, 20 Acanthamoeba genotypes have been
      described. Genotype T4 is responsible for approximately 90% of encephalitis and
      keratitis cases. Due to the ubiquitous presence of amoebae, isolation from
      environmental sources is not uncommon; to determine the clinical importance of an
      isolation, it is necessary to have evidence of the pathogenic potential of
      amoebae. OBJECTIVE: The aim of this study was to physiologically characterise 8
      Acanthamoeba T4 isolates obtained from dental units and emergency combination
      showers and to determine their pathogenic potential by employing different
      laboratory techniques. METHODS: Eight axenic cultures of Acanthamoeba genotype T4
      were used in pathogenic potential assays. Osmotolerance, thermotolerance,
      determination and characterisation of extracellular proteases and evaluation of
      cytopathic effects in MDCK cells were performed. FINDINGS: All of the isolates
      were osmotolerant, thermotolerant and had serine proteases from 44-122 kDa. Two
      isolates had cytopathic effects on the MDCK cell monolayer. MAIN CONCLUSION: The
      presence of Acanthamoeba T4 with pathogenic potential in areas such as those
      tested in this study reaffirms the need for adequate cleaning and maintenance
      protocols to reduce the possibility of infection with free-living amoebae.

PMID- 29211243
TI  - Evidence of hidden leprosy in a supposedly low endemic area of Brazil.
AB  - OBJECTIVES: Show that hidden endemic leprosy exists in a municipality of inner
      Sao Paulo state (Brazil) with active surveillance actions based on clinical and
      immunological evaluations. METHODS: The study sample was composed by people
      randomly selected by a dermatologist during medical care in the public emergency
      department and by active surveillance carried out during two days at a mobile
      clinic. All subjects received a dermato-neurological examination and blood
      sampling to determine anti-PGL-I antibody titers by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: From July to December 2015, 24 new cases of leprosy were
      diagnosed; all were classified as multibacillary (MB) leprosy, one with severe
      Lucio's phenomenon. Seventeen (75%) were found with grade-1 or 2 disability at
      the moment of diagnosis. Anti-PGL-I titer was positive in 31/133 (23.3%)
      individuals, only 6/24 (25%) were positive in newly diagnosed leprosy cases.
      CONCLUSIONS: During the last ten years before this study, the average new case
      detection rate (NCDR) in this town was 2.62/100,000 population. After our work,
      the NCDR was raised to 42.8/100,000. These results indicate a very high number of
      hidden leprosy cases in this supposedly low endemic area of Brazil.

PMID- 29211244
TI  - Dengue serotype-specific immune response in Aedes aegypti and Aedes albopictus.
AB  - BACKGROUND: Dengue viruses (DENV) are considered one of the most important
      emerging pathogens and dengue disease is a global health threat. The geographic
      expansion of dengue viruses has led to co-circulation of all four dengue
      serotypes making it imperative that new DENV control strategies be devised.
      OBJECTIVES: Here we characterize dengue serotype-specific innate immune responses
      in Aedes aegypti and Aedes albopictus using DENV from Puerto Rico (PR). METHODS:
      Ae. aegypti and Ae. albopictus were infected with dengue serotype 1 and 2
      isolated from Puerto Rico. DENV infected mosquito samples were collected and
      temporal change in expression of selected innate immune response pathway genes
      analyzed by quantitative real time PCR. FINDINGS: The Toll pathway is involved in
      anti-dengue response in Ae. aegypti, and Ae. albopictus. Infections with PR DENV-
      1 elicited a stronger response from genes of the Toll immune pathway than PR DENV
      2 in Ae. aegypti but in infected Ae. albopictus expression of Toll pathway genes
      tended to be similar between the serotypes. Two genes (a ribosomal S5 protein
      gene and a nimrod-like gene) from Ae. albopictus were expressed in response to
      DENV. MAIN CONCLUSIONS: These studies revealed a role for antiviral genes in DENV
      serotype-specific interactions with DENV vectors, demonstrated that infections
      with DENV-2 can modulate the Toll immune response pathway in Ae. aegypti and
      elucidated candidate molecules that might be used to interfere with serotype
      specific vector-virus interactions.

PMID- 29211245
TI  - Low dose systemic or intralesional meglumine antimoniate treatment for American
      tegumentary leishmaniasis results in low lethality, low incidence of relapse, and
      low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001
      2013).
AB  - BACKGROUND: American tegumentary leishmaniasis (ATL) is a non-lethal parasitic
      disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL
      treatment aims at healing the lesions and preventing the development of the late
      mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg
      Sb5+/kg/day is the first choice of treatment. However, alternative therapies
      using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the
      National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil.
      OBJECTIVES: To evaluate lethality and the incidence of relapse and development of
      late ML in CL patients treated at NIID from 2001 until 2013. METHODS: Data were
      recovered from records of all ATL patients diagnosed during that period.
      FINDINGS: Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1%
      received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some
      patients required 1-3 additional courses of treatment, thus making a total of 997
      courses; 85.2% of them were subjected to alternative therapies. Lethality was
      0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for
      the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow
      up. MAIN CONCLUSIONS: Alternative MA schedules resulted in low lethality without
      increase of relapse or late ML incidence.

PMID- 29211246
TI  - ELISA-based assay of immunoglobulin G antibodies against mammalian cell entry 1A
      (Mce1A) protein: a novel diagnostic approach for leprosy.
AB  - BACKGROUND: Leprosy is a chronic infectious disease caused by the obligate
      intracellular bacillus Mycobacterium leprae. Because leprosy diagnosis is complex
      and requires professional expertise, new tools and methodologies are needed to
      detect cases in early stages and prevent transmission. The M. leprae genome
      contains mce1A, which encodes a putative mammalian cell entry protein (Mce1A). We
      hypothesised that the presence of Mce1A on the cell surface could be detected by
      the host's immune system. OBJECTIVE: The aim of this study was to evaluate
      antibody responses against the Mce1A protein in leprosy patients, household
      contacts of patients, and the general population to present an addition tool for
      leprosy diagnosis. METHODS: A cross-sectional study involving 89 volunteers [55
      leprosy cases, 12 household contacts (HHC) and 22 endemic controls (EC)] was
      conducted at Couto Maia Hospital, in Salvador, Bahia (BA), Brazil. RESULTS: The
      median anti-Mce1A IgA was significantly higher in multibacillary (MB) and
      paucibacillary (PB) cases than in EC (p < 0.0001). A similar trend was observed
      in IgM levels, which were significantly higher in both MB (p < 0.0001) and PB (p
      = 0.0006) groups compared to in EC individuals. The greatest differences were
      observed for IgG class-specific antibodies against Mce1A. The median levels of MB
      and PB were significantly higher compared to both controls HHC and EC (MB or PB
      vs EC, MB vs HHC p < 0.0001; PB vs HHC, p = 0.0013). Among leprosy cases, IgG
      enzyme-linked immunosorbent assay sensitivity and specificity were 92.7% and
      97.1%, respectively. IgG positivity was confirmed in 92.1% and 94.1% of MB and PB
      patients, respectively. CONCLUSION: This novel diagnostic approach presents an
      easy, non-invasive, and inexpensive method for leprosy screening, which may be
      applicable in endemic areas.

PMID- 29211247
TI  - Immunoproteomics of Plasmodium falciparum-infected red blood cell membrane
      fractions.
AB  - BACKGROUND: The surface of infected red blood cells (iRBCs) has been widely
      investigated because of the molecular complexity and pathogenesis mechanisms
      involved. Asymptomatic individuals are important in the field because they can
      perpetuate transmission as natural reservoirs and present a challenge for
      diagnosing malaria because of their low levels of circulating parasites. Recent
      studies of iRBC antibody recognition have shown that responses are quantitatively
      similar in symptomatic and asymptomatic infections, but no studies have
      characterised the plasmodial proteins targeted by this response. OBJECTIVES: Our
      main objective was to identify Plasmodium falciparum proteins associated with
      iRBC ghosts recognised by antibodies in the sera of symptomatic and asymptomatic
      individuals in the Brazilian Amazon. METHODS: We collected symptomatic and
      asymptomatic sera from patients residing in the Brazilian Amazon and P.
      falciparum iRBC ghosts to identify the proteins involved in natural antibody
      recognition by 2D-electrophoresis, western blotting, and high- resolution mass
      spectrometry. FINDINGS: 2D gel-based immunoproteome analysis using symptomatic
      and asymptomatic sera identified 11 proteins with at least one unique peptide,
      such as chaperones HSP70-1 and HSP70-x, which likely are components of the
      secretion machinery/PTEX translocon. PfEMP1 is involved in antigenic variation in
      symptomatic infections and we found putative membrane proteins whose functions
      are unknown. MAIN FINDINGS: Our results suggest a potential role of old and new
      proteins, such as antigenic variation proteins, iRBC remodelling, and membrane
      proteins, with no assigned functions related to the immune response against P.
      falciparum, providing insights into the pathogenesis, erythrocyte remodelling,
      and secretion machinery important for alternative diagnosis and/or malaria
      therapy.

PMID- 29211248
TI  - Draft genome of the emerging pathogen, Kocuria marina, isolated from a wild urban
      rat.
AB  - Kocuria marina has recently emerged as a cause for catheter-related bloodstream
      infections in patients with underlying health complications. One K. marina strain
      was recently isolated from the lung tissues of a wild urban rat (Rattus rattus
      diardii) caught during rodent surveillance. Here, we present the draft genome of
      the first K. marina animal isolate, K. marina TRE150902.

PMID- 29211250
TI  - Modulation of the prostaglandin-endoperoxide synthase 2 gene expression by
      variant haplotypes: influence of the 3'-untranslated region.
AB  - The inducible inflammatory enzyme cycloxigenase-2 is up-regulated in cancer, and
      favors tumor progression. Cycloxigenase-2 is encoded by the prostaglandin
      endoperoxide synthase 2 (PTGS2) gene, which presents sequence variations in the
      promoter region (PR) and in the 3'-untranslated region (3'-UTR). Different PR
      (rs689465, rs689466, rs20417) and 3'-UTR (rs5275) variants were generated by site
      directed mutagenesis, and combined in haplotypes to access expression levels
      using a reporter system (luciferase) in human cells (MCF-7 and HEK293FT).
      Luciferase activity did not differ significantly among PTGS2 PR constructs,
      except for pAAC (containing variant allele rs20417 C), with 40% less activity
      than pAAG (wild-type sequence) in MCF-7 cells (P<0.01). Despite the lack of
      individual significant differences, PTGS2 PR constructs enclosing rs689466 G
      (pAGG and pAGC) showed an approximate two-fold increase in luciferase activity
      when compared to those containing rs689466 A (pAAG, pGAC, pAAC and pGAG) in both
      cell lines (P<0.001 for MCF-7 and P=0.03 for HEK293FT). The effect of PTGS2 3'
      UTR sequences varied between MCF-7 and HEK293FT: MCF-7 cells showed significant
      reduction (40-60%) in luciferase activity (at least P<0.01), whereas HEK293FT
      cells showed more diverse results, with an average 2-fold increase when combined
      constructs (PR and 3'-UTR) were compared to respective parental PR sequences. The
      contribution of 3'-UTR variant (rs5275) was not consistent in either cell line.
      Despite the modulation of the 3'-UTR, with variable effects of rs5275, the
      enhancing transcriptional effect of rs689466 G was still detectable (P<0.0001 in
      MCF-7 or P=0.03 in HEK293FT cells).

PMID- 29211249
TI  - Effects of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth
      factor (VEGF) release from polylactide-poly (ethylene glycol)-polylactide (PELA)
      microcapsule-based scaffolds on bone.
AB  - Multiple growth factors can be administered to mimic the natural process of bone
      healing in bone tissue engineering. We investigated the effects of sequential
      release of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth
      factor (VEGF) from polylactide-poly (ethylene glycol)-polylactide (PELA)
      microcapsule-based scaffolds on bone regeneration. To improve the double
      emulsion/solvent evaporation technique, VEGF was encapsulated in PELA
      microcapsules, to which BMP-2 was attached. The scaffold (BMP-2/PELA/VEGF) was
      then fused to these microcapsules using the dichloromethane vapor method. The
      bioactivity of the released BMP-2 and VEGF was then quantified in rat mesenchymal
      stem cells (rMSCs). Immunoblotting analysis showed that BMP-2/PELA/VEG promoted
      the differentiation of rMSCs into osteoblasts via the MAPK and Wnt pathways.
      Osteoblast differentiation was assessed through alkaline phosphatase expression.
      When compared with simple BMP-2 plus VEGF group and pure PELA group, osteoblast
      differentiation in BMP-2/PELA/VEGF group significantly increased. An MTT assay
      indicated that BMP-2-loaded PELA scaffolds had no adverse effects on cell
      activity. BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblast
      via the ERK1/2 and Wnt pathways. Our findings indicate that the sequential
      release of BMP-2 and VEGF from PELA microcapsule-based scaffolds is a promising
      approach for the treatment of bone defects.

PMID- 29211251
TI  - Circulating levels of adiponectin and extent of coronary artery disease in
      patients undergoing elective coronary angiography.
AB  - Adiponectin (APN), an adipose tissue-released adipokine with demonstrated anti
      inflammatory and anti-atherogenic properties, is encoded by a gene whose
      polymorphisms are associated with presence of coronary artery disease (CAD).
      Serum APN levels are inversely related with presence and complexity of CAD.
      Within this context, we sought to compare levels of total APN and its high
      molecular weight form (HMW APN) according to clinical presentation and extent of
      CAD in patients undergoing elective cardiac catheterization. From March 2008 to
      June 2010, clinical data and blood samples for APN and HMW APN measurements were
      collected from 415 subjects undergoing cardiac catheterization at two tertiary
      centers. CAD extent was estimated by the number of coronary arteries with
      significant stenosis (>=70% obstruction in a major coronary artery) and by Duke
      Jeopardy Score (DJS). Serum APN levels were similar between groups with stable or
      unstable CAD (APN 9.20+/-5.88 vs 9.47+/-6.23 MUg/mL, P=0.738, and HMW APN 5.31+/
      3.72 vs 5.91+/-4.16 MUg/mL, P=0.255), even after stratification by the number of
      arteries involved (single-vessel vs multivessel disease: APN 9.39+/-5.76 vs
      9.26+/-6.27 MUg/mL, P=0.871; HMW APN 5.29+/-3.79 vs 5.83+/-4.04 MUg/mL, P=0.306)
      and DJS score (APN, P=0.718; HMW APN, P=0.276). We conclude that APN and HMW APN
      serum levels are similar across clinical presentations and different extents of
      CAD, despite being significantly lower in the presence of obstructive CAD.

PMID- 29211253
TI  - Leaving no child with disability behind.

PMID- 29211252
TI  - Ilex paraguariensis extracts extend the lifespan of Drosophila melanogaster fed a
      high-fat diet.
AB  - Studies have suggested that total energy intake and diet composition affect
      lifespan and ageing. A high-fat diet induces oxidative stress and affects the
      development of diseases. In contrast, antioxidants are capable of reducing its
      harmful effects. Yerba mate beverages are an important source of antioxidants,
      but there is scarce knowledge about their effects on suppressing fat
      accumulation. Here, we investigated the compounds present in yerba mate extracts
      and assessed their effects on Drosophila melanogaster given a high cholesterol
      diet. LS-ESI-MS analysis showed the presence of matesaponins, phenolic compounds
      and methylxanthines in all of the examined extracts. In Drosophila, under extract
      treatment conditions, the mean lifespan was significantly extended from 38 to 43
      days, there was an increase in the ability to support induced stress and decrease
      in lipid peroxidation products. Moreover, yerba mate extracts recovered the
      glutathione S-transferases (GST) activity and reduced the cholesterol level.
      Taken together, our results support that extracts can extend lifespan by reducing
      the detrimental effect of a high-fat diet in D. melanogaster, and this outcome
      can be associated with the compound content in the extracts. This study improves
      the understanding of natural interventions that reduce stress-induced oxidative
      damage, which is fundamental in promoting healthy ageing.

PMID- 29211254
TI  - [Mental health in the populational field: the utopia of social psychiatry in low
      income countries].

PMID- 29211255
TI  - Severe functional difficulties and disabilities in children and adolescents and
      the Sustainable Development Goals.
AB  - OBJECTIVE: To report prevalence of severe child functional difficulties and
      disability (CFD) in a nationally representative sample of 2 to 17 year-old
      children in Mexico and describe the inequities faced by children with CFD in
      relation to a set of Sustainable Development Goals (SDG)-related outcomes.
      MATERIALS AND METHODS: Using data from the National Survey of Children and Women
      (ENIM 2015) we estimate prevalence with 95% confidence intervals for the selected
      indicators. We use chi-square test and confidence intervals inspection to report
      significant differences between children with and without CFD. RESULTS: 8% of
      children present at least one CFD. CFD is associated with higher prevalence of
      underweight and child labor and lower prevalence of adequate early child
      development. Conclusion. Children with CFD present worst outcomes and require
      targeted efforts to ensure they meet health and wellbeing targets in the frame of
      the SDGs.

PMID- 29211256
TI  - Population profiles associated with severe functioning difficulties and
      disability among two to four years old children in Mexico.
AB  - OBJECTIVE: To describe the prevalence and factors associated with severe child
      functioning difficulties and disability (CFD) among two to four year old children
      in Mexico, and estimates the probability of presenting CFD based on specific
      population profiles. MATERIALS AND METHODS: The sample consists of 5 104 children
      who participated in the National Survey of Children and Women 2015 (ENIM). We
      used post-estimation exploration by computing predicted values of CFD to
      interpret the logistic models for discrete combinations of the independent
      variables. RESULTS: CFD prevalence is 2%, which means at least 130 000 two to
      four year-old children are at risk of experiencing severely limited participation
      in an unaccommodating environment. The probability of presenting CFD is
      dramatically higher in specific sub-groups of the population, in particular, male
      children of women with low education, who live in the poorest households.
      CONCLUSIONS: A significant proportion of Mexican children face important
      challenges due to functioning difficulties and disability. Public policies must
      be developed to accommodate the needs of these children and provide a proper
      environment for their development.

PMID- 29211257
TI  - Population profiles associated with severe functional difficulties and disability
      among 5-17 years-old children in Mexico.
AB  - OBJECTIVES: To report the prevalence of severe functional difficulties and
      disability (SFD) in a nationally representative sample of children ages 5 to 17
      in Mexico, to identify factors associated with SFD, and population profiles
      predictive of SFD. MATERIALS AND METHODS: Using data from the National Survey on
      Children and Women we estimated prevalence and 95% confidence intervals of SFD
      and risk factors. We fitted bivariate and multivariate logistic regression
      models. We then examined which combinations of the sociodemographic factors best
      predicted SFD. RESULTS: The prevalence of SFD was 11.2%. The most prevalent SFD
      were on the socioemotional dimension (8.3%). The associated risk factors in the
      three dimensions were: living in a poor household, being a boy, having a mother
      with basic education or less, and non-indigenous background or living in an urban
      area. CONCLUSIONS: Identifying groups of the population at higher risk for SFD
      provides useful information for targeted intervention implementation.

PMID- 29211258
TI  - Child labor and severe functioning difficulties and disability in Mexican
      children and adolescents 5-17 years of age.
AB  - OBJECTIVE: To describe the characteristics of Mexican children and adolescents 5
      17 years with severe functioning difficulties and disability and explore their
      participation in child labor. MATERIALS AND METHODS: Using data from the National
      Survey of Boys, Girls and Women in Mexico 2015 we estimated prevalence of
      functioning difficulties and disability and used logistic regression to explore
      the association between this condition and child labor. RESULTS: While 11.2% of
      Mexicans 5-17 years-old has severe functioning difficulties or disability, 13.4%
      work. The functioning difficulty and disability domains with the highest
      prevalence are experiencing anxiety (5.4%) and depression (1.5%) daily. Children
      and adolescents with severe functioning difficulties and disability are 70% more
      likely to do child labor [OR=1.7, 95%CI:1.2,2.4]. Educational lag doubles the
      likelihood of doing child labor [OR=2.2, 95%CI:1.5,3.3]. CONCLUSIONS:
      Guaranteeing educational opportunities and respect for the rights of children
      with severe functioning difficulties and disability is essential to achieve
      development of their full potential.

PMID- 29211259
TI  - Prevalence of functioning difficulties and disability in Mexican adolescent women
      and their populational characteristics.
AB  - OBJECTIVE: Report prevalence of functioning difficulties and disabilities among
      Mexican adolescent women 15-17 years old and identify differences in
      characteristics of those with and without a functioning difficulty or disability.
      MATERIALS AND METHODS: Using data from the National Survey of Boys, Girls and
      Women in Mexico 2015 we estimated prevalence of functioning difficulties and
      disability and used chi square tests for independence and logistic regression to
      explore associations between this condition and various characteristics. RESULTS:
      Of Mexican adolescent women 15-17 years old, 11.1% had a functioning difficulty
      or disability. The group of domains of functioning difficulty and disability with
      by far the highest prevalence was socio-emotional and behavioral functioning
      difficulties or disability with 8.6%. Being employed, rural residence and self
      reported depression symptoms were associated with having functioning difficulties
      or disability. CONCLUSIONS: This survey constitutes an important initial step in
      collecting data on functioning difficulty and disability in Mexico although
      larger samples should be studied.

PMID- 29211260
TI  - Health profiles in people with intellectual developmental disorders.
AB  - OBJECTIVE: To better understand the health profiles of people with intellectual
      disability (ID), focusing on the variables that are associated with a poorer
      health status. MATERIALS AND METHODS: Data were collected from the Survey on
      Disability, Personal Autonomy and Dependency (EDAD 2008) of the Spanish National
      Statistics Institute (INE). The health data of 2840 subjects with IDD were
      analyzed in order to verify the impact of different variables on their health
      profiles. RESULTS: People with severe and profound levels of IDD presented a
      higher number of medical diagnoses. At residence centers there was a larger
      proportion of individuals with a higher prevalence of chronic diseases and more
      severe conditions; age also was an important factor. CONCLUSION: The health
      profiles of individuals with IDD differ depending on the severity level of their
      IDD and their degree of institutionalization. Further research is needed to
      provide better health care for people with IDD.

PMID- 29211261
TI  - [Hospital admissions and morbidity in people with intellectual developmental
      disorders].
AB  - OBJECTIVE: People with intellectual developmental disorders (IDD) have worse
      health statuses in comparison with general population. The objective of this
      paper is to compare access and hospital morbimortality in people with IDD and
      general population. MATERIAL AND METHODS: We conducted a retrospective cross
      sectional analytical study and analyzed data on admissions and discharges between
      IDD patients and the rest of them, in Ciudad Real, Espana. RESULTS: Out of 51 325
      hospital admissions, 441 (0.9%) belonged to the group of persons with IDD. The
      IDD group had fewer programmed hospitalization than the general population and
      fewer surgical interventions. They presented more admissions for mental disorders
      and respiratory system diseases. CONCLUSIONS: The data presented confirm TDI
      population have different patterns of disease. Furthermore, this study reveal
      potential difficulties in access to health care in this population.

PMID- 29211262
TI  - Body mass index and waist circumference of Latin American adult athletes with
      intellectual disability.
AB  - OBJECTIVES: To examine both body mass index (BMI) status and waist circunference
      (WC) in a large international sample of adult Special Olympics participants from
      Latin America. It also explored the association of age and sex with obesity in
      this population. MATERIALS AND METHODS: BMI and WC records from a total of 4174
      (2683 male and 1491 female) participant records from the Special Olympics
      International Health Promotion database were examined. RESULTS: The prevalence of
      overweight and obesity was quite high (i.e. > 40%), but generally lower than
      studies involving adults with intellectual disabilities from Europe and the USA.
      Chi-square analyses revealed that both increasing age and being female
      significantly predicted levels of overweight, obesity, and WC. CONCLUSIONS: These
      results suggest that efforts need to be made to prevent and reduce rates of
      overweight and obesity among Latin American Special Olympics participants,
      particularly women.

PMID- 29211263
TI  - Metabolic screening and metabolomics analysis in the Intellectual Developmental
      Disorders Mexico Study.
AB  - OBJECTIVE: Inborn errors of metabolism (IEM) are genetic conditions that are
      sometimes associated with intellectual developmental disorders (IDD). The aim of
      this study is to contribute to the metabolic characterization of IDD of unknown
      etiology in Mexico. MATERIALS AND METHODS: Metabolic screening using tandem mass
      spectrometry and fluorometry will be performed to rule out IEM. In addition,
      target metabolomic analysis will be done to characterize the metabolomic profile
      of patients with IDD. CONCLUSION: Identification of new metabolomic profiles
      associated with IDD of unknown etiology and comorbidities will contribute to the
      development of novel diagnostic and therapeutic schemes for the prevention and
      treatment of IDD in Mexico.

PMID- 29211264
TI  - Disability in Mexico: a comparative analysis between descriptive models and
      historical periods using a timeline.
AB  - Some interpretations frequently argue that three Disability Models (DM) (Charity,
      Medical/Rehabilitation, and Social) correspond to historical periods in terms of
      chronological succession. These views permeate a priori within major official
      documents on the subject in Mexico. This paper intends to test whether this
      association is plausible by applying a timeline method. A document search was
      made with inclusion and exclusion criteria in databases to select representative
      studies with which to depict milestones in the timelines for each period. The
      following is demonstrated: 1) models should be considered as categories of
      analysis and not as historical periods, in that the prevalence of elements of the
      three models is present to date, and 2) the association between disability models
      and historical periods results in teleological interpretations of the history of
      disability in Mexico.

PMID- 29211265
TI  - Interventions to promote physical activity for youth with intellectual
      disabilities.
AB  - OBJECTIVE: To describe interventions designed to promote physical activity for
      youth with intellectual disabilities. MATERIALS AND METHODS: A systematic review
      of nine databases until January 31, 2015 identified 213 citations. The inclusion
      criteria were: a) the study sample consisted of youth with intellectual
      disabilities, b) the study implemented an intervention to initiate, increase, or
      maintain physical activity, and c) quantitative or qualitative data were used to
      report the effectiveness of the intervention. Eleven articles from the 213
      citations met this criterion. RESULTS: Nine studies reported significant
      increases in physical activity behavior. CONCLUSIONS: Conclusions cannot be made
      regarding intervention components that impacted outcome variables, if the
      observed effects were specifically due to the intervention or if interventions
      could be maintained long-term. To advance the knowledge base in this area, a
      concerted effort should be made to increase rigor in study conceptualization and
      research design.

PMID- 29211266
TI  - Interventions to promote physical activity for adults with intellectual
      disabilities.
AB  - OBJECTIVE: To describe interventions designed to promote physical activity for
      adults with intellectual disabilities and the effects on overall physical
      activity levels and on health outcomes. MATERIALS AND METHODS: A systematic
      review of eight databases until January 31, 2015 identified 383 citations. The
      inclusion criteria were: a) the study sample consisted of adults with
      intellectual disabilities, b) the study implemented an intervention to initiate,
      increase, or maintain physical activity, and c) quantitative or qualitative data
      were used to report the effectiveness of the intervention. Six articles from the
      383 citations met this criterion. RESULTS: Three studies resulted in significant
      increases in physical activity behaviour; however well-controlled trials designed
      to improve weight status by increasing physical activity did not produce
      significant effects. CONCLUSION: Overall, the results indicate that interventions
      to increase physical activity should simultaneously target the individual with
      intellectual disability as well as their proximal environment over a sustained
      period of time.

PMID- 29211267
TI  - [New considerations on the health of the persons with intellectual developmental
      disorders].
AB  - Recent literature indicates that people with Disorders of Intellectual
      Development (DID) experience health disparities in the pathologies that they
      present, and a worst access to health care. However, current evidence-based
      knowledge is still sparse outside the Anglo-Saxon countries. The POMONA-I and
      POMONA-II European projects aimed to collect information on the health status of
      people with DID in Europe. The POMONA-ESP project in Spain is meant to collect
      health information in a wide and representative sample of persons with DID. Also,
      there are studies that claim for the need of specialized services for people with
      DID at the public health system. There are also studies about the current state
      of the education and training about DID for students within the health sector. In
      this paper we review the latest evidences about the health of the persons with
      DID and we present the main research activities and care initiatives about this
      issue.

PMID- 29211268
TI  - Consent to care of persons with intellectual disability in Quebec: from
      vulnerability to capability.
AB  - Persons with an intellectual disability (ID) who interact with the Quebec health
      and social services system are faced with major decisions regarding the care they
      are offered. As consent to care derives from the fundamental right of all persons
      to personal inviolability and to autonomous decision making, they therefore have
      the right to accept or refuse any and all health and psychosocial care proposed.
      However, as free and informed consent to care must be given by an able person,
      the situation becomes somewhat more complicated whereas persons with ID are
      concerned. This article presents reflections on the challenges and issues
      relative to these persons' consent to health and psychosocial care.

PMID- 29211269
TI  - [Processes of attention to children and adolescents under 20 years in La
      Castaneda: evolution of the concept of childhood in psychiatry].
AB  - Today, there is evidence that shows that children and adolescents can experience
      developmental problems and psychiatric disorders. This was possible because of
      two main reasons, the evolution of the concept of infancy and the progress made
      in medical and psychiatric diagnostic classification. This manuscript offers a
      glance to early psychiatric attention in Mexico, particularly the care processes
      provided to 36 children and adolescents under twenty, admitted in the mental
      asylum La Castaneda, during the first half of the XX century. Admission causes,
      length of stay, diagnosis, treatment and discharge motives, are some of the
      aspects described in this study. Finally, it also reflects about the challenge it
      is for a child psychiatric hospital nowadays, with such a history, to become an
      innovative institution able to claim a place in the medical field in favor of
      those minors that can barely defend themselves.

PMID- 29211270
TI  - [Children's Psychiatric Hospital Dr. Juan N. Navarro: 50 years of attention to
      the mental health of children and adolescents in Mexico].
AB  - The activities concerning mental health care of psychiatric disorders during more
      than 50 years of service (1966-2016) at the Children's Psychiatric Hospital "Dr.
      Juan N. Navarro" (HPI), as well as the progressive development of teaching and
      research, have contributed to its positioning as a leading institution in medical
      care of high specialization. This has been possible through the training of human
      resources that focus the quality of care to the children and their families. The
      hospital has progressed towards diagnostic and therapeutic care of outpatients
      through the creation of specialized clinics (emotions, behavior, development,
      adolescence, among others) and the development of more actualized and integral
      therapeutic programs (behavioral psychotherapy, cognitive behavioral,
      psychodynamic; individual, group, family, etc.). In the field of education, the
      hospital has been the most important institution in the training of child
      psychiatrists in Mexico and its recognition as a research interdisciplinary
      center has grown.

PMID- 29211271
TI  - Measuring child functioning: the Unicef/ Washington Group Module.

PMID- 29211272
TI  - [Intermittent hemodialysis].

PMID- 29211273
TI  - [Type 2 diabetes mellitus and primary knee osteoarthritis].

PMID- 29211274
TI  - [Fragility is not associated with a low frequency of vaccination in older
      adults].

PMID- 29211275
TI  - The impact of Popular Health Insurance "Seguro Popular" on diabetes mortality in
      Mexico, 1999-2014.

PMID- 29211276
TI  - [Deafhood, a new way of thinking and living deafness].

PMID- 29211277
TI  - [Reproductive and sexual health as a reflection of inequity in indigenous women
      from the mountain region of Guerrero, Mexico].

PMID- 29211278
TI  - JAOS under a continuous publication workflow in 2018.

PMID- 29211279
TI  - Effects of chlorhexidine preprocedural rinse on bacteremia in periodontal
      patients: a randomized clinical trial.
AB  - OBJECTIVE: Single dose of systemic antibiotics and short-term use of mouthwashes
      reduce bacteremia. However, the effects of a single dose of preprocedural rinse
      are still controversial. This study evaluated, in periodontally diseased
      patients, the effects of a pre-procedural mouth rinse on induced bacteremia.
      MATERIAL AND METHODS: Systemically healthy individuals with gingivitis (n=27) or
      periodontitis (n = 27) were randomly allocated through a sealed envelope system
      to: 0.12% chlorhexidine pre-procedural rinse (13 gingivitis and 13 periodontitis
      patients) or no rinse before dental scaling (14 gingivitis and 15 periodontitis
      patients). Periodontal probing depth, clinical attachment level, plaque, and
      gingival indices were measured and subgingival samples were collected. Blood
      samples were collected before dental scaling, 2 and 6 minutes after scaling.
      Total bacterial load and levels of P. gingivalis were determined in oral and
      blood samples by real-time polymerase chain reaction, while aerobic and anaerobic
      counts were determined by culture in blood samples. The primary outcome was the
      antimicrobial effect of the pre-procedural rinse. Data was compared by Mann
      Whitney and Signal tests (p<0.05). RESULTS: In all sampling times, polymerase
      chain reaction revealed higher blood bacterial levels than culture (p<0.0001),
      while gingivitis patients presented lower bacterial levels in blood than
      periodontitis patients (p<0.0001). Individuals who experienced bacteremia showed
      worse mean clinical attachment level (3.4 mm vs. 1.1 mm) and more subgingival
      bacteria (p<0.005). The pre-procedural rinse did not reduce induced bacteremia.
      CONCLUSIONS: Bacteremia was influenced by periodontal parameters. In
      periodontally diseased patients, pre-procedural rinsing showed a discrete effect
      on bacteremia control.

PMID- 29211280
TI  - In vitro effect of amorphous calcium phosphate paste applied for extended periods
      of time on enamel remineralization.
AB  - OBJECTIVES: Dental applications based on the unique characteristics of amorphous
      calcium phosphate stabilized by casein phosphopeptides (CPP-ACP) have been
      proposed, as well as the improvement of its properties. The objective of this
      study was to determine the ability of topically applied CPP-ACP from a commercial
      product to remineralize subsurface lesions when applied for extended periods of
      time (3 h and 8 h). MATERIAL AND METHODS: Artificially induced carious lesions
      were produced in 50 bovine enamel blocks previously selected by surface hardness.
      After treatments with gel without F and CPP-ACP applied for 1 minute (Placebo);
      2% NaF neutral gel applied for 1 minute (Fluoride 1 min); CPP-ACP applied for 3
      min (ACP 3 min); and CPP-ACP applied for 3 h (ACP 3 h) and for 8 h (ACP 8 h), the
      enamel blocks were submitted to the remineralization pH-cycling. Surface hardness
      and synchrotron micro-tomography were used to determine the percentage of surface
      hardness recovery (%SHR) and to calculate mineral concentration (gHAp.cm-3),
      respectively. The data were submitted to ANOVA followed by the Student-Newman
      Keuls test (p<0.05). RESULTS: Fluoride gel presented higher %SHR followed by ACP
      3 min (p<0.001). No difference (p = 0.148) was found for Placebo, ACP 3 h and ACP
      8 h groups for %SHR. Fluoride gel showed greater mineral concentration (p<0.001)
      when compared with the other groups. ACP 3 min demonstrated a significant
      difference (p<0.001) from ACP 3 h and ACP 8 h. The ACP 3 h and 8 h presented a
      subsurface lesion with development of laminations in all blocks. CONCLUSION: In
      this in vitro study the use of CPP-ACP for extended periods of time did not
      produce an additive effect in the remineralization process.

PMID- 29211281
TI  - Effect of fluoride dentifrice and casein phosphopeptide-amorphous calcium
      phosphate cream with and without fluoride in preventing enamel demineralization
      in a pH cyclic study.
AB  - OBJECTIVE: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complexes
      are anticariogenic and capable of remineralizing the early stages of enamel
      lesions. The use of fluoride prevents dental decay and the association of CPP-ACP
      with fluoride can increase remineralization. To evaluate the effect of CPP-ACP
      and CPP-ACPF creams associated with a fluoride dentifrice to prevent enamel
      demineralization in a pH cyclic model. MATERIAL AND METHODS: Previously selected
      by surface microhardness (SH) analysis, human enamel blocks (n = 56) were
      submitted to daily treatment with dentifrice in a pH-cycling model. The enamel
      blocks were divided into four groups; G1: CrestTM Cavity Protection - Procter &
      Gamble (1,100 ppmF of NaF); G2: CrestTM +MI Paste (MP) - RecaldentTM GC
      Corporation Tokyo, Japan); G3: CrestTM + MI Paste Plus (MPP) - RecaldentTM 900
      ppm as NaF, GC Corporation Tokyo, Japan), and G4: control, saliva. Specimens were
      soaked alternatively in a demineralizing solution and in artificial saliva for 5
      d. The fluoride dentifrice, with proportion of 1:3 (w/w), was applied three times
      for 60 s after the remineralization period. The undiluted MP and MPP creams were
      applied for 3 m/d. After cycling, SH was re-measured and cross section
      microhardness measurements were taken. RESULTS: The SH values observed for the
      groups G3 (257+/-70), G1 (205+/-70), and G2 (208+/-84) differed from the G4 group
      (98+/-110) (one-way ANOVA and Tukey's post hoc test). There were no differences
      between the groups G1xG2, G2xG3, and G1xG3 for demineralization inhibition. The
      percentage of volume mineral showed that, when applied with fluoride dentifrice,
      MPP was the most effective in preventing enamel demineralization at 50 u from the
      outer enamel surface (Kruskal-Wallis and Mann Whitney p<0.05). CONCLUSION:
      Fluoride dentifrice associated with CPP-ACPF inhibited subsurface enamel
      demineralization.

PMID- 29211282
TI  - Apical Negative Pressure irrigation presents tissue compatibility in immature
      teeth.
AB  - AIM: To compare the apical negative pressure irrigation (ANP) with conventional
      irrigation in the teeth of immature dogs with apical periodontitis. METHODS:
      Fifty-two immature pre-molar root canals were randomly assigned into 4 groups:
      ANP (n=15); conventional irrigation (n=17); healthy teeth (control) (n = 10); and
      teeth with untreated apical periodontitis (control) (n=10). After induction of
      apical periodontitis, teeth were instrumented using EndoVac(r) (apical negative
      pressure irrigation) or conventional irrigation. The animals were euthanized
      after 90 days. The sections were stained by HE and analyzed under conventional
      and fluorescence microscopy. TRAP histoenzymology was also performed. Statistical
      analyses were performed with the significance level set at 5%. RESULTS: There was
      difference in the histopathological parameters between ANP and conventional
      groups (p<0.05). The ANP group showed a predominance of low magnitude
      inflammatory infiltrate, a smaller periodontal ligament, and lower mineralized
      tissue resorption. There were no differences in the periapical lesion extensions
      between the ANP and conventional groups (p>0.05). However, a lower number of
      osteoclasts was observed in the ANP group (p<0.05). CONCLUSION: The EndoVac(r)
      irrigation system presented better biological results and more advanced repair
      process in immature teeth with apical periodontitis than the conventional
      irrigation system, confirming the hypothesis.

PMID- 29211283
TI  - Systemic effect of mineral aggregate-based cements: histopathological analysis in
      rats.
AB  - OBJECTIVE: Several studies reported the local tissue reaction caused by mineral
      aggregate-based cements. However, few studies have investigated the systemic
      effects promoted by these cements on liver and kidney when directly applied to
      connective tissue. The purpose of this in vivo study was to investigate the
      systemic effect of mineral aggregate-based cements on the livers and kidneys of
      rats. MATERIAL AND METHODS: Samples of Mineral Trioxide Aggregate (MTA) and a
      calcium aluminate-based cement (EndoBinder) containing different radiopacifiers
      were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of
      subcutaneous, liver and kidney tissues were submitted to histopathological
      analysis. A score (0-3) was used to grade the inflammatory reaction. Blood
      samples were collected to evaluate changes in hepatic and renal functions of
      animals. RESULTS: The moderate inflammatory reaction (2) observed for 7 d in the
      subcutaneous tissue decreased with time for all cements. The thickness of
      inflammatory capsules also presented a significant decrease with time (P<.05).
      Systemically, all cements caused adverse inflammatory reactions in the liver and
      kidney, being more evident for MTA, persisting until the end of the analysis.
      Liver functions increased significantly for MTA during 30 d (P<.05). CONCLUSION:
      The different cements induced to a locally limited inflammatory reaction.
      However, from the systemic point of view, the cements promoted significant
      inflammatory reactions in the liver and kidney. For MTA, the reactions were more
      accentuated.

PMID- 29211284
TI  - Effects of triethylene glycol dimethacrylate (TEGDMA) on the odontoclastic
      differentiation ability of human dental pulp cells.
AB  - OBJECTIVES: The primary purpose of this study was to examine the effects of
      triethylene glycol dimethacrylate (TEGDMA) on odontoclastic differentiation in
      the dental pulp tissue. MATERIAL AND METHODS: The effects of different TEGDMA
      dosages on the odontoclastic differentiation capability of dental pulp cells were
      analyzed in vitro using the following methodologies: i) flow cytometry and
      tartrate-resistant acid phosphatase (TRAP) staining; ii) apoptotic effects using
      Annexin V staining; iii) mRNA expression of osteoprotegerin (OPG) and receptor
      activator of nuclear factor (NF)-kB ligand (RANKL) genes by quantitative Real
      time PCR (qRT-PCR); and iv) OPG and RANKL protein expression by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: TEGDMA caused relatively less odontoclastic
      differentiation in comparison with the control group; however, odontoclastic
      differentiation augmented with increasing doses of TEGDMA (p<0.05). The mRNA and
      protein expression of OPG was lower in TEGDMA treated pulp cells than in the
      control group (p<0.05). While the mRNA expression of RANKL remained unchanged
      compared to the control group (p>0.05), its protein expression was higher than
      the control group (p<0.05). In addition, TEGDMA increased the apoptosis of dental
      pulp cells dose dependently. CONCLUSIONS: TEGDMA reduced the odontoclastic
      differentiation ability of human dental pulp cells. However, odontoclastic
      differentiation ratios increased proportionally with the increasing dose of
      TEGDMA.

PMID- 29211285
TI  - Intradentinal antimicrobial action and filling quality promoted by ultrasonic
      agitation of epoxy resin-based sealer in endodontic obturation.
AB  - MATERIAL AND METHODS: The aim of this study was evaluate the influence of
      ultrasonic activation (UA) of AH Plus to improve canal and isthmus filing, and
      analyse the antimicrobial effect against Enterococcus faecalis within dentinal
      tubules. Thirty mesial roots of mandibular first molars were selected and divided
      into 2 groups (n = 15): with and without UA of the sealer. Then the root canals
      were filled by using the single cone technique, and the specimens were sectioned
      at 2, 4 and 6 mm from the apex for stereomicroscope and confocal laser scanner
      microscopy (CLSM) analysis. In addition, 30 bovine incisors were contaminated
      with Enterococcus faecalis and divided into 3 groups (n = 10). The specimens were
      obturated by using the single cone technique with (G1) and without (G2) UA of the
      sealer and G3 as the control group. All were sectioned into 6 mm-long cylinders
      and stained with LIVE/DEAD to assess bacterial viability by CLSM. RESULTS: The UA
      of the sealer significantly reduced the presence of unfilled areas in the canal
      and isthmus area in all sections (p<0.05), and there was a significant increase
      in sealer penetration in both canals and isthmuses (p<0.05). As regards gaps, a
      significant reduction was found at 2 and 6 mm in the isthmus area of the UA group
      (p<0.05). Moreover, UA of the sealer significantly reduced bacterial viability in
      the superficial dentine when compared with the other groups (p<0.05). CONCLUSION:
      Ultrasonic activation of the AH Plus sealer promoted a better quality of root
      canal filling and increased the intratubular penetration of sealer, especially in
      the isthmus area. Additionally, ultrasonic activation of the sealer increased the
      intradentinal antimicrobial action against Enterococcus faecalis, mainly in the
      superficial dentine of the root canal.

PMID- 29211286
TI  - Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non
      Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast
      Iranian population.
AB  - OBJECTIVES: Non-syndromic cleft lip with or without palate (NSCL/P) is a common
      congenital malformation worldwide, with complex etiology. It has been proposed
      that interaction of genes and environmental factors play a role in the
      predisposition to this disease. The aim of this study was to examine the
      association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone
      morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6)
      rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. MATERIAL
      AND METHODS: This case-control study was carried out on 132 unrelated NSCL/P
      patients and 156 healthy subjects. The variants were genotyped using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The
      findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk
      of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11,
      95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p =
      0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs
      CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and
      allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our
      findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019
      polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not
      polymorphic in our population. CONCLUSION: The results indicate that the BMP4
      rs17563 variant is likely to confer a protective effect against the occurrence of
      NSCL/P in a sample of the southeast Iranian population.

PMID- 29211287
TI  - Comparative study between laser and conventional techniques for class V cavity
      preparation in gamma-irradiated teeth (in vitro study).
AB  - OBJECTIVE: The purpose of this study was to compare laser with conventional
      techniques in class V cavity preparation in gamma-irradiated teeth. METHODS:
      Forty extracted human teeth with no carious lesions were used for this study and
      were divided into two main groups: Group I (n = 20) was not subjected to gamma
      radiation (control) and Group II (n=20) was subjected to gamma radiation of 60
      Gray. Standard class V preparation was performed in buccal and lingual sides of
      each tooth in both groups. Buccal surfaces were prepared by the Er,Cr:YSGG laser
      (Waterlase iPlus) 2780 nm, using the gold handpiece with MZ10 Tip in non-contact
      and the "H" mode, following parameters of cavity preparation - power 6 W,
      frequency 50 Hz, 90% water and 70% air, then shifting to surface treatment laser
      parameters - power 4.5 W, frequency 50 Hz, 80% water and 50% air. Lingual
      surfaces were prepared by the conventional high-speed turbine using round diamond
      bur. Teeth were then sectioned mesio-distally, resulting in 80 specimens: 40 of
      which were buccal laser-treated (20 control and 20 gamma-irradiated specimens)
      and 40 were lingual conventional high-speed bur specimens (20 control and 20
      gamma-irradiated specimens). RESULTS: Microleakage analysis revealed higher
      scores in both gamma groups compared with control groups. Chi-square test
      revealed no significant difference between both control groups and gamma groups
      (p=1, 0.819, respectively). A significant difference was revealed between all 4
      groups (p=0.00018). CONCLUSION: Both laser and conventional high-speed turbine
      bur show good bond strength in control (non-gamma) group, while microleakage is
      evident in gamma group, indicating that gamma radiation had a dramatic negative
      effect on the bond strength in both laser and bur-treated teeth.

PMID- 29211288
TI  - Pre-sintered Y-TZP sandblasting: effect on surface roughness, phase
      transformation, and Y-TZP/veneer bond strength.
AB  - OBJECTIVES.: Sandblasting is a common method to try to improve the Y-TZP/veneer
      bond strength of dental prostheses, however, it may put stress on zirconia
      surfaces and could accelerate the t->m phase transformation. Y-TZP sandblasting
      before sintering could be an alternative to improve surface roughness and bonding
      strength of veneering ceramic. The aim of this study was to analyze the effect of
      Y-TZP pre-sintering sandblasting on surface roughness, phase transformation, and
      the Y-TZP/veneer shear bond strength. MATERIAL AND METHODS.: The Y-TZP specimen
      surface underwent sandblasting with aluminum oxide (50 MUm) pre-sintering (Z-PRE)
      and post-sintering (Z-POS). Z-CTR was not subjected to surface treatment. After
      ceramic veneer application, the specimens were subjected to shear bond testing.
      Surface roughness was analyzed by confocal microscopy. Y-TZP monoclinic and
      tetragonal phases were evaluated by micro-Raman spectroscopy. Shear bond strength
      and surface roughness data were analyzed by One-way ANOVA and Tukey tests
      (alpha=0.05). Differences in the wave numbers and the broadening bands of the
      Raman spectra were compared among groups. RESULTS.: Z-POS (9.73+/-5.36 MPa) and Z
      PRE (7.94+/-2.52 MPa) showed the highest bond strength, significantly higher than
      that of Z-CTR (5.54+/-2.14 MPa). The Ra of Z-PRE (1.59+/-0.23 um) was much
      greater and significantly different from that of Z-CTR (0.29+/-0.05 um) and Z-POS
      (0.77+/-0.13 um). All groups showed bands typical of the tetragonal (T) and
      monoclinic (M) phases. Y-TZP sandblasting before sintering resulted in rougher
      surfaces but did not increase the shear bond strength compared to post-sintering
      and increased surface defects. CONCLUSIONS.: Surface treatment with Al3O2,
      regardless of the moment and application, improves the results of Y-TZP/veneer
      bonding and is not a specific cause of t->m transformation.

PMID- 29211289
TI  - Comparison of automatic and visual methods used for image segmentation in
      Endodontics: a microCT study.
AB  - OBJECTIVE: To calculate root canal volume and surface area in microCT images, an
      image segmentation by selecting threshold values is required, which can be
      determined by visual or automatic methods. Visual determination is influenced by
      the operator's visual acuity, while the automatic method is done entirely by
      computer algorithms. To compare between visual and automatic segmentation, and to
      determine the influence of the operator's visual acuity on the reproducibility of
      root canal volume and area measurements. MATERIAL AND METHODS: Images from 31
      extracted human anterior teeth were scanned with a MUCT scanner. Three
      experienced examiners performed visual image segmentation, and threshold values
      were recorded. Automatic segmentation was done using the "Automatic Threshold
      Tool" available in the dedicated software provided by the scanner's manufacturer.
      Volume and area measurements were performed using the threshold values determined
      both visually and automatically. RESULTS: The paired Student's t-test showed no
      significant difference between visual and automatic segmentation methods
      regarding root canal volume measurements (p=0.93) and root canal surface
      (p=0.79). CONCLUSION: Although visual and automatic segmentation methods can be
      used to determine the threshold and calculate root canal volume and surface, the
      automatic method may be the most suitable for ensuring the reproducibility of
      threshold determination.

PMID- 29211290
TI  - Physical properties and biological effects of mineral trioxide aggregate mixed
      with methylcellulose and calcium chloride.
AB  - OBJECTIVES: Methylcellulose (MC) is a chemical compound derived from cellulose.
      MTA mixed with MC reduces setting time and increases plasticity. This study
      assessed the influence of MC as an anti-washout ingredient and CaCl2 as a setting
      time accelerator on the physical and biological properties of MTA. MATERIAL AND
      METHODS: Test materials were divided into 3 groups; Group 1(control): distilled
      water; Group 2: 1% MC/CaCl2; Group 3: 2% MC/CaCl2. Compressive strength, pH,
      flowability and cell viability were tested. The gene expression of bone
      sialoprotein (BSP) was detected by RT-PCR and real- time PCR. The expression of
      alkaline phosphatase (ALP) and mineralization behavior were evaluated using an
      ALP staining and an alizarin red staining. RESULTS: Compressive strength, pH, and
      cell viability of MTA mixed with MC/CaCl2 were not significantly different
      compared to the control group. The flowability of MTA with MC/CaCI2 has decreased
      significantly when compared to the control (p<.05). The mRNA level of BSP has
      increased significantly in MTA with MC/CaCl2 compared to the control (p<.05).
      This study revealed higher expression of ALP and mineralization in cells exposed
      to MTA mixed with water and MTA mixed with MC/CaCl2 compared to the control
      (p<.05). CONCLUSIONS: MC decreased the flowability of MTA and did not interrupt
      the physical and biological effect of MTA. It suggests that these cements may be
      useful as a root-end filling material.

PMID- 29211291
TI  - Topical application of bFGF on acid-conditioned and non-conditioned dentin:
      effect on cell proliferation and gene expression in cells relevant for
      periodontal regeneration.
AB  - MATERIAL AND METHODS: Periodontal regeneration is still a challenge in terms of
      predictability and magnitude of effect. In this study we assess the biological
      effects of combining chemical root conditioning and biological mediators on three
      relevant cell types for periodontal regeneration. Bovine dentin slices were
      conditioned with 25% citric acid followed by topical application of basic
      fibroblast growth factor (bFGF, 10 and 50 ng). We used ELISA to assess the
      dynamics of bFGF release from the dentin surface and RT-qPCR to study the
      expression of Runx2, Col1a1, Bglap and fibronectin by periodontal ligament (PDL)
      fibroblasts, cementoblasts and bone marrow stromal cells (BMSC) grown onto these
      dentin slices. We also assessed the effects of topical application of bFGF on
      cell proliferation by quantification of genomic DNA. RESULTS: Acid conditioning
      significantly increased the release of bFGF from dentin slices. Overall, bFGF
      application significantly (p<0.05) increased cell proliferation, except for BMSC
      grown on non-conditioned dentin slices. Dentin substrate discretely increased
      expression of Col1a1 in all cell types. Expression of Runx2, Col1a1 and Fn was
      either unaffected or inhibited by bFGF application in all cell types. We could
      not detect expression of the target genes on BMSC grown onto conditioned dentin.
      CONCLUSION: Acid conditioning of dentin improves the release of topically-applied
      bFGF. Topical application of bFGF had a stimulatory effect on proliferation of
      PDL fibroblasts, cementoblasts and BMSC, but did not affect expression of Runx2,
      Col1a1, Bglap and fibronectin by these cells.

PMID- 29211292
TI  - Influence of curing protocol and ceramic composition on the degree of conversion
      of resin cement.
AB  - OBJECTIVE: Due to increasing of aesthetic demand, ceramic crowns are widely used
      in different situations. However, to obtain long-term prognosis of restorations,
      a good conversion of resin cement is necessary. To evaluate the degree of
      conversion (DC) of one light-cure and two dual-cure resin cements under a
      simulated clinical cementation of ceramic crowns. MATERIAL AND METHODS: Prepared
      teeth were randomly split according to the ceramic's material, resin cement and
      curing protocol. The crowns were cemented as per manufacturer's directions and
      photoactivated either from occlusal suface only for 60 s; or from the buccal,
      occlusal and lingual surfaces, with an exposure time of 20 s on each aspect.
      After cementation, the specimens were stored in deionized water at 37 degrees C
      for 7 days. Specimens were transversally sectioned from occlusal to cervical
      surfaces and the DC was determined along the cement line with three measurements
      taken and averaged from the buccal, lingual and approximal aspects using micro
      Raman spectroscopy (Alpha 300R/WITec(r)). Data were analyzed by 3-way ANOVA and
      Tukey test at =5%. RESULTS: Statistical analysis showed significant differences
      among cements, curing protocols and ceramic type (p<0.001). The curing protocol
      3x20 resulted in higher DC for all tested conditions; lower DC was observed for
      Zr ceramic crowns; Duolink resin cement culminated in higher DC regardless
      ceramic composition and curing protocol. CONCLUSION: The DC of resin cement
      layers was dependent on the curing protocol and type of ceramic.

PMID- 29211293
TI  - Oral cancer stem cells - properties and consequences.
AB  - Research on cancer stem cells (CSCs) has greatly increased in the field of
      medicine and pathology; however, some conceptual misunderstandings are still
      present among the public as well as within the general scientific community that
      is not yet familiar with the subject. The very first problem is the
      misinterpretation of CSCs as a synonym of their normal counterparts, the well
      known stem cells (SCs). Particularly in Dentistry, another common mistake is the
      misinterpretation of oral CSCs as normal tooth-derived SCs. The present review
      aims to clarify important concepts related to normal SCs and CSCs, as well as
      discuss the relevance of CSCs to the development, metastasis and therapy
      resistance of oral squamous cell carcinoma.

PMID- 29211294
TI  - Single-Cell Analysis Using Hyperspectral Imaging Modalities.
AB  - Almost a decade ago, hyperspectral imaging (HSI) was employed by the NASA in
      satellite imaging applications such as remote sensing technology. This technology
      has since been extensively used in the exploration of minerals, agricultural
      purposes, water resources, and urban development needs. Due to recent
      advancements in optical re-construction and imaging, HSI can now be applied down
      to micro- and nanometer scales possibly allowing for exquisite control and
      analysis of single cell to complex biological systems. This short review provides
      a description of the working principle of the HSI technology and how HSI can be
      used to assist, substitute, and validate traditional imaging technologies. This
      is followed by a description of the use of HSI for biological analysis and
      medical diagnostics with emphasis on single-cell analysis using HSI.

PMID- 29211296
TI  - "Epigenetic" modification as therapy for acute myeloid leukemia.

PMID- 29211295
TI  - Phase 2 study of treatment selection based on tumor thymidylate synthase
      expression in previously untreated patients with metastatic colorectal cancer: A
      trial of the ECOG-ACRIN Cancer Research Group (E4203).
AB  - BACKGROUND: The authors hypothesized that patients with metastatic colorectal
      cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression
      would have a higher response rate to combined 5-fluorouracil, leucovorin, and
      oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H)
      expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab
      (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors.
      METHODS: TS protein expression was determined in mCRC tissue. Patients who had TS
      L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly
      assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the
      response rate (complete plus partial responses). RESULTS: In total, 211 of 247
      patients (70% TS-H) were registered to the treatment phase. Efficacy analyses
      included eligible patients who had started treatment (N = 186). The response
      rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and
      FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The
      median progression-free survival (PFS) was 10 months (95% confidence interval
      [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the
      FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L
      group had improved PFS compared with the TS-H group that received FOLFOX/Bev
      (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median
      overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the
      IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the
      TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H
      versus TS-L arms were not significantly different. CONCLUSIONS: TS expression was
      prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS
      than those with TS-H tumors, along with a trend toward longer OS. Patients with
      TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer
      2018;124:688-97. (c) 2017 American Cancer Society.

PMID- 29211297
TI  - Immune checkpoint inhibitors in advanced non-small cell lung cancer.
AB  - The emergence of immune checkpoint inhibitors for the treatment of cancer has led
      to major changes to the therapeutic landscape of lung cancer. Improvements in
      overall survival relative to standard chemotherapy have been observed in the
      first-line and second-line therapy settings for patients with advanced non-small
      cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors.
      Consequently, every patient with advanced-stage NSCLC is now a candidate for
      immune checkpoint inhibitor therapy. However, it is clear that the benefit from
      therapy is not universal, and identification of biomarkers to select therapy has
      assumed importance. In addition to programmed cell death receptor ligand 1
      expression, both tissue-based and blood-based markers are under evaluation to
      select patients. In an era of increasing costs of care and potential for
      toxicities related to immune checkpoint inhibition, proper patient selection is
      critical to the optimal use of this new class of agents. In addition, development
      of novel combination approaches has also emerged as an important way to improve
      the efficacy of immune checkpoint inhibition. Studies in earlier stages of NSCLC
      are already underway with the hope of improving the cure rate. In this article,
      the authors review the current landscape of immune checkpoint inhibitors in the
      treatment of advanced NSCLC. Cancer 2018;124:248-61. (c) 2017 American Cancer
      Society.

PMID- 29211298
TI  - Prognostic relevance of early radiologic response to induction chemotherapy in
      pediatric rhabdomyosarcoma: A report from the International Society of Pediatric
      Oncology Malignant Mesenchymal Tumor 95 study.
AB  - BACKGROUND: Early response to induction chemotherapy is used in current European
      guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt
      treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing
      literature on the prognostic value of early radiologic response on survival is
      contradictory; here the prognostic value is analyzed with data from the
      International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95
      (MMT-95) study. METHODS: This study examined 432 Intergroup Rhabdomyosarcoma
      Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95
      study with a response assessment after 3 courses of chemotherapy (a 2-dimensional
      assessment). Patients with progressive disease (PD) after 3 courses of
      chemotherapy were excluded (n = 7). Failure-free survival (FFS) and overall
      survival (OS), calculated with the Kaplan-Meier method, were compared for 3
      groups (complete response [CR]/partial response [PR], objective response [OR],
      and no response [NR]). The prognostic impact of early response was assessed
      through the calculation of Cox proportional hazards. RESULTS: After 3 courses of
      chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For
      all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI],
      56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional
      hazards regression analysis revealed no significant difference in FFS or OS
      between the response groups. The adjusted hazard ratios for an OR and NR were
      1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and
      0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS.
      CONCLUSIONS: No evidence was found for the idea that early radiologic response to
      chemotherapy is prognostic for survival for patients with RMS. Treatment
      adaptation based on early response (except for patients with PD) should,
      therefore, no longer be incorporated into future studies. Cancer 2018;124:1016
      24. (c) 2017 American Cancer Society.

PMID- 29211300
TI  - Fluorine-Directed Glycosylation Enables the Stereocontrolled Synthesis of
      Selective SGLT2 Inhibitors for Type II Diabetes.
AB  - Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated
      strategy to address the increasing prevalence of type II diabetes mellitus.
      However, achieving selective inhibition of human SGLT1 or SGLT2 remains
      challenging. Orally available small molecule drugs based on the d-glucose core of
      the natural product Gliflozin have proven to be clinically effective in this
      regard, effectively impeding glucose reabsorption. Herein, we disclose the
      influence of molecular editing with fluorine at the C2 position of the pyranose
      ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga(r)
      ) to concurrently direct beta-selective glycosylation, as is required for
      biological efficacy, and enhance aspects of the physicochemical profile. Given
      the abundance of glycosylated pharmaceuticals in diabetes therapy that contain a
      beta-configured d-glucose nucleus, it is envisaged that this strategy may prove
      to be expansive.

PMID- 29211299
TI  - Endoplasmic reticulum stress induced LOX-1+  CD15+ polymorphonuclear myeloid
      derived suppressor cells in hepatocellular carcinoma.
AB  - A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a
      distinct surface marker for human polymorphisms myeloid-derived suppressor cells
      (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN
      MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC
      patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis
      due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health
      control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC
      patients compared with healthy control and patients with benign diseases. LOX-1+ 
      CD15+ PMN-MDSC in circulation were positively associated with those in HCC
      tissues. LOX-1+  CD15+ PMN-MDSCs significantly reduced proliferation and IFN
      gamma production of T cells with a dosage dependent manner with LOX-1-  CD15+
      PMNs reached negative results. The suppression on T cell proliferation and IFN
      gamma production was reversed by ROS inhibitor and Arginase inhibitor. ROS level
      and activity of arginase of LOX-1 + CD15+ PMN were higher in LOX-1+  CD15+ PMN
      MDSCs than LOX-1-  CD15+ PMNs, as well as the expression of the NADPH oxidase
      NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed
      significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an
      endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1
      expression and suppressive function for CD15+ PMN from health donor. For HCC
      patients, LOX-1+  CD15+ PMN-MDSCs were positively related to overall survival.
      Above all, LOX-1+  CD15+ PMN-MDSC were elevated in HCC patients and suppressed T
      cell proliferation through ROS/Arg I pathway induced by ER stress. They presented
      positive association with the prognosis of HCC patients.

PMID- 29211301
TI  - Outcome in patients with left common pulmonary vein after cryoablation with
      second-generation cryoballoon.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) has become a widely accepted therapy
      in patients suffering from symptomatic atrial fibrillation (AF). HYPOTHESIS: AF
      free survival differs in patients with left common pulmonary vein (LCPV) after
      PVI with second-generation cryoballoon. METHODS: We included patients scheduled
      for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented
      arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3
      month blanking period. RESULTS: We observed a LCPV in 37 of 270 consecutive
      patients (13.7%). Analyses were performed in a 1:1 propensity score matched
      cohort of 68 patients. During a median follow-up of 77.0 weeks, 37 patients
      (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in
      patients with AF recurrence (62.2% vs 35.5%, P  =  0.051) and Kaplan-Meier
      analysis showed lower AF-free survival in patients with existence of a LCPV (P  =
      0.028). At 1-year follow-up, 70.6% of patients without versus 55.1% of patients
      with LCPV were free of AF. Multivariate Cox regression analysis revealed presence
      of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and
      mitral regurgitation > I degrees  (HR: 2.571) as predictors of AF recurrence.
      CONCLUSION: Patients with LCPV had significantly reduced AF-free survival after
      ablation with the second-generation cryoballoon, despite similar acutely
      successful PVIs.

PMID- 29211302
TI  - Adoption of evidence-based novel therapies in the treatment of gastric cancer: A
      national observational study.
AB  - BACKGROUND: The adoption of novel and effective gastric cancer therapies into
      general clinical practice has crucial implications for patient outcomes. The
      current study explored trends in treatment use and overall survival in patients
      with gastric cancer in the United States. METHODS: Patients with adenocarcinoma
      of the gastric cardia and noncardia were identified in the National Cancer Data
      Base between 2006 and 2014. Tumor stages were divided into early (IA), locally
      advanced (IB-IIIC), and metastatic (IV) stage. Treatment use was examined
      according to tumor stage and location. Time trend analyses of treatment use and
      overall survival were conducted. RESULTS: A total of 89,098 patients with gastric
      adenocarcinoma were identified. In those with early-stage cancer, endoscopic
      treatment increased over time in patients with cardia and noncardia disease. In
      patients with locally advanced cardia disease, preoperative therapy use increased
      over time (2013-2014 [vs 2006-2008]: odds ratio [OR], 3.09; 95% confidence
      interval [95% CI], 2.80-3.41). In patients with locally advanced noncardia
      disease, the use of preoperative therapy also increased (2013-2014: OR, 3.32; 95%
      CI, 2.88-3.82) as did the use of perioperative therapy (2013-2014: OR, 4.21; 95%
      CI, 3.52-5.03) in lieu of postoperative treatment (2013-2014: OR, 0.66; 95% CI,
      0.60-0.71). In patients with metastatic disease, approximately 34% of patients
      with cardia and 40% of patients with noncardia cancer did not receive treatment.
      Stage-specific and location-specific overall survival was found to improve over
      the study period. CONCLUSIONS: Practice patterns for the treatment of gastric
      cancer in the United States reflect the increased adoption of evidence-based
      therapies, including endoscopic resection of early-stage cancer and preoperative
      therapy for patients with locally advanced disease. Treatment for metastatic
      disease remains markedly underused. Cancer 2018;124:1122-31. (c) 2017 American
      Cancer Society.

PMID- 29211304
TI  - Risk of recurrence, prognosis, and follow-up for Danish women with cervical
      cancer in 2005-2013: A national cohort study.
AB  - BACKGROUND: In developed countries, women attend follow-up after treatment for
      cervical cancer to detect recurrence. The aim of this study was to describe the
      Danish population of women with early-stage cervical cancer at risk for
      recurrence and death due to recurrence. METHODS: Data were extracted from 3
      nationwide databases to find women diagnosed with stage 1A1 to 1B1 cervical
      cancer in 2005-2013. Recurrences were determined from data on oncological or
      surgical treatment more than 3 months after the initial diagnosis and were cross
      checked with patient journals. RESULTS: In all, 1523 patients were diagnosed with
      stage 1A1 to 1B1 cervical cancer. Eighty women experienced recurrences: 8 at
      International Federation of Gynecology and Obstetrics (FIGO) stage 1A1, 0 at FIGO
      stage 1A2, and 72 at FIGO stage 1B1. The 5-year recurrence rate was 6.4%; 67.5%
      of the women had symptomatic recurrences, and 28.8% had asymptomatic recurrences.
      At significantly greater risk for recurrence were women at stage 1B1, regardless
      of their lymph node (LN) status at diagnosis (hazard ratio with a positive LN,
      5.10; 95% confidence interval [CI], 1.65-15.76; P = .0047; hazard ratio with a
      negative LN, 3.14; 95% CI, 1.25-7.93; P = .0153; hazard ratio with LN data
      missing, 6.33; 95% CI, 1.80-22.26; P = .004), women older than 50 years (hazard
      ratio, 1.81; 95% CI, 1.12-2.94; P = .0158), and women with lymphatic and
      lymphovascular space invasion (LVSI; hazard ratio, 1.92; 95% CI, 1.11-3.30; P =
      .0188). In a multivariate analysis, significantly inferior survival was found
      after recurrence for patients with lymphatic LVSI (hazard ratio, 2.23; 95% CI,
      1.04-4.80; P = .0401), a symptomatic diagnosis of recurrence (hazard ratio, 2.52;
      95% CI, 1.08-5.90; P = .0332), and multiple sites of recurrence (hazard ratio,
      2.72; 95% CI, 1.32-5.61; P = .0066). CONCLUSIONS: This study has identified a
      group of women at FIGO stage 1A1 in no need of specialized, hospital-based follow
      up. Many of the recurrences at FIGO stage 1B1 are asymptomatic, and this may show
      a need for follow-up in this group. Further prospective investigation is needed.
      Cancer 2018;124:943-51. (c) 2017 American Cancer Society.

PMID- 29211305
TI  - Improving bone health in men with prostate cancer receiving androgen deprivation
      therapy: Results of a randomized phase 2 trial.
AB  - BACKGROUND: Strategies to improve bone health care in men receiving androgen
      deprivation therapy (ADT) are not consistently implemented. The authors conducted
      a phase 2 randomized controlled trial of 2 education-based models-of-care
      interventions to determine their feasibility and ability to improve bone health
      care. METHODS: A single-center parallel-group randomized controlled trial of men
      with prostate cancer who were receiving ADT was performed. Participants were
      randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations
      for their family physician (BHP+FP); 2) a BHP and support from a bone health care
      coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was
      receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy
      outcomes included guideline-appropriate calcium and vitamin D use and
      bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints
      included recruitment, retention, satisfaction, contamination, and outcome
      capture. The main analysis used logistic regression with a 1-sided P of .10. The
      trial is registered at ClinicalTrials.gov (identifier NCT02043236). RESULTS: A
      total of 119 men were recruited. The BHP+BHCC strategy was associated with a
      greater percentage of men undergoing a BMD test compared with the usual-care
      group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the
      BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with
      higher percentages of patients using calcium and vitamin D, but only the BHP+FP
      arm was statistically significant (P = .039). No men were detected to be at high
      fracture risk. All but one feasibility endpoint was met. CONCLUSIONS: Educational
      strategies to improve bone health care appear feasible and are associated with
      improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. (c) 2017
      American Cancer Society.

PMID- 29211303
TI  - Evaluating antidisease immunity to malaria and implications for vaccine design.
AB  - Immunity to malaria could be categorized broadly as antiparasite or antidisease
      immunity. While most vaccine research efforts have focused on antiparasite
      immunity, the evidence from endemic populations suggest that antidisease immunity
      is an important component of natural immunity to malaria. The processes that
      mediate antidisease immunity have, however, attracted little to no attention, and
      most interests have been directed towards the antibody responses. This review
      evaluates the evidence for antidisease immunity in endemic areas and discusses
      the possible mechanisms responsible for it. Given the key role that inflammation
      plays in the pathogenesis of malaria, regulation of the inflammatory response
      appears to be a major mechanism for antidisease immunity in naturally exposed
      individuals.

PMID- 29211306
TI  - Telomerase reverse transcriptase promoter alterations across cancer types as
      detected by next-generation sequencing: A clinical and molecular analysis of 423
      patients.
AB  - BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations that may
      affect telomerase activity have recently been described in human malignancies.
      The purpose of this study was to investigate the clinical correlates of TERT
      promoter abnormalities in a large cohort of patients with diverse cancers.
      METHODS: This study analyzed TERT promoter alterations and clinical
      characteristics of 423 consecutive patients for whom molecular testing by next
      generation sequencing was performed between August 2014 and July 2015. RESULTS:
      Of the 423 patients, 61 (14.4%) had TERT promoter mutations, and this placed TERT
      promoter alterations among the most prevalent aberrations after tumor protein 53
      (TP53; 39%) and KRAS and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B)
      alterations (15% each) in this population. TERT promoter alterations were more
      frequent in men (P = .031) and were associated with brain cancers (P = .001),
      skin cancers/melanoma (P = .001), and a higher number of aberrations (P = .0001).
      A co-alteration analysis found that TERT promoter alterations were significantly
      correlated with CDKN2A/B (P = .001) and BRAF abnormalities (P = .0003). Patients
      harboring TERT promoter alterations or TP53 or CDKN2A/B alterations and those
      with 4 or more alterations demonstrated shorter survival (hazard ratio for normal
      TERT promoters vs aberrant ones, 0.44; P = .017). However, only a higher number
      of alterations remained significant in the multivariate analysis. CONCLUSIONS:
      Overall, TERT promoter alterations were among the most prevalent aberrations in
      this population, with very high rates in brain cancers (48% of patients) and
      melanomas (56% of patients). These aberrations frequently coexist with a high
      number of other aberrations, with the latter feature also significantly
      associated with poorer overall survival. Therapeutic options for targeting tumors
      with TERT promoter mutations are currently limited, although a variety of novel
      approaches are under development. Cancer 2018;124:1288-96. (c) 2017 American
      Cancer Society.

PMID- 29211307
TI  - Temporal changes in treatments and outcomes after acute myocardial infarction
      among cancer survivors and patients without cancer, 1995 to 2013.
AB  - BACKGROUND: There is a paucity of information about treatment and mortality
      trends after acute myocardial infarction (AMI) for cancer survivors (CS).
      METHODS: In this population-based study, the authors compared temporal trends of
      treatments and outcomes (mortality, nonfatal cardiovascular outcomes), among CS
      and patients without cancer (the noncancer patient [NCP] group) with AMI in
      Ontario (Canada) using inverse probability treatment weight (IPTW)-adjusted
      modeling. RESULTS: Of 270,089 patients with AMI (22,907 CS, 247,182 NCP, 1995
      2013; median follow-up, 10.1 and 11.0 years, respectively), the use of invasive
      coronary strategies and pharmacotherapies increased and mortality declined for CS
      and NCP (all Ptrend  < .001). At 30 days after AMI, there was no difference
      between CS and NCP in the receipt of coronary angiography (incidence risk ratio
      [IRR], 0.98; 95% confidence interval [CI], 0.96-1.01; P = .23), percutaneous
      coronary intervention (IRR, 0.98; 95% CI, 0.94-1.02; P = .29), or bypass (IRR,
      0.93; 95% CI, 0.85-1.02; P = .11). At 90 days after AMI, there was no difference
      in the receipt of beta-blockers, clopidogrel, or nitrates; but CS were less often
      prescribed angiotensin-converting enzyme inhibitors/angiotensin II receptor
      blockers and statins. CS had higher all-cause mortality at 30 days (adjusted
      hazard ratio [HR] 1.12; 95% CI, 1.07-1.17; P < .001), at 1 year (1.16; 95% CI,
      1.12-1.20; P < .001), and long term (HR, 1.21; 95% CI, 1.17-1.25; P < .001) and
      had a greater risk of heart failure (HR, 1.08; 95% CI, 1.03-1.14; P = .001), but
      not myocardial re-infarction (HR, 0.98; 95% CI, 0.95-1.01; P = .22) or stroke
      (HR, 1.06; 95% CI, 0.97-1.16; P = .18). CONCLUSIONS: Among CS and NCP with AMI in
      Ontario, similar improvements in mortality and receipt of treatments were
      observed between 1995 and 2013. However, compared with NCP, CS had a higher risk
      of mortality and heart failure. Cancer 2018;124:1269-78. (c) 2017 American Cancer
      Society.

PMID- 29211308
TI  - Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory
      acute myeloid leukemia.
AB  - BACKGROUND: Outcomes for patients with relapsed or refractory acute myeloid
      leukemia (AML) are poor. Guadecitabine, a next-generation hypomethylating agent,
      could be useful in treating such patients. METHODS: In this multicenter, open
      label, phase 2 dose-expansion study, AML patients from 10 North American medical
      centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60
      or 90 mg/m2 on 5 consecutive days in each 28-day cycle (5-day regimen).
      Subsequently, another cohort was treated for 10 days with 60 mg/m2 (10-day
      regimen). RESULTS: Between June 15, 2012, and August 19, 2013, 108 patients with
      previously treated AML consented to enroll in the study, and 103 of these
      patients were treated; 5 patients did not receive the study treatment. A total of
      103 patients were included in the safety and efficacy analyses (24 and 26
      patients who were randomly assigned to 60 and 90 mg/m2 /d, respectively [5-day
      regimen] and 53 patients who were assigned to 60 mg/m2 /d [10-day regimen]). The
      90 mg/m2 dose showed no benefit in clinical outcomes in comparison with 60 mg/m2
      in the randomized cohort. Composite complete response (CRc) and complete response
      (CR) rates were higher with the 10-day regimen versus the 5-day regimen (CRc,
      30.2% vs 16.0%; P = .1061; CR, 18.9% vs 8%; P = .15). Adverse events (grade >= 3)
      were mainly hematologic, with a higher incidence on the 10-day regimen. Early all
      cause mortality was low and similar between regimens. Twenty patients (8 on the 5
      day regimen and 12 on the 10-day regimen) were bridged to hematopoietic cell
      transplantation. CONCLUSIONS: Guadecitabine has promising clinical activity and
      an acceptable safety profile and thus warrants further development in this
      population. Cancer 2018;124:325-34. (c) 2017 The Authors. Cancer published by
      Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open
      access article under the terms of the Creative Commons Attribution NonCommercial
      License, which permits use, distribution and reproduction in any medium, provided
      the original work is properly cited and is not used for commercial purposes.

PMID- 29211309
TI  - Statins in nonsurgical and surgical periodontal therapy. A systematic review and
      meta-analysis of preclinical in vivo trials.
AB  - The cholesterol-lowering drugs, statins, possess anti-inflammatory, antimicrobial
      and pro-osteogenic properties, and thus have been tested as an adjunct to
      periodontal treatment. The present systematic review aimed to answer the
      following focused research question: What is the effect of local and/or systemic
      statin use on periodontal tissues in preclinical in vivo studies of
      experimentally induced periodontitis (EIP) and/or acute/chronified periodontal
      defect (ACP) models? A literature search (of Medline/PubMed, Embase/Ovid,
      CENTRAL/Ovid) using the following main eligibility criteria was performed: (i)
      English or German language; (ii) controlled preclinical in vivo trials; (iii)
      local and/or systemic statin use in EIP and/or ACP models; and (iv) quantitative
      evaluation of periodontal tissues (i.e., alveolar bone level/amount, attachment
      level, cementum formation, periodontal ligament formation). Sixteen studies in
      EIP models and 7 studies in ACP models evaluated simvastatin, atorvastatin or
      rosuvastatin. Thirteen of the EIP (81%) and 2 of the ACP (29%) studies presented
      significantly better results in terms of alveolar bone level/amount in favor of
      statins. Meta-analysis based on 14 EIP trials confirmed a significant benefit of
      local and systemic statin use (P < .001) in terms of alveolar bone level/amount;
      meta-regression revealed that statin type exhibited a significant effect (P =
      .014) in favor of atorvastatin. Three studies reported a significantly higher
      periodontal attachment level in favor of statin use (P < .001). Complete
      periodontal regeneration was never observed; furthermore, statins did not exert
      any apparent effect on cementum formation. Neither local nor systemic use of
      statins resulted in severe adverse effects. Statin use in periodontal indications
      has a positive effect on periodontal tissue parameters, supporting the positive
      results already observed in clinical trials. Nevertheless, not all statins
      available have been tested so far, and further research is needed to identify the
      maximum effective concentration/dose and optimal carrier.

PMID- 29211310
TI  - Presentation and outcome of frequent and rare sarcoma histologic subtypes: A
      study of 10,262 patients with localized visceral/soft tissue sarcoma managed in
      reference centers.
AB  - BACKGROUND: The objective of this study was to describe characteristics at
      diagnosis and outcomes of adults with soft tissue sarcoma. METHODS: The authors
      conducted a retrospective multicenter study of 12,262 patients who were treated
      between January 1980 and 31 December 2013 in French Sarcoma Group centers and
      enrolled in the "Conticabase." Diagnoses were systematically reviewed by expert
      pathologists, and entities were classified according to the 2013 World Health
      Organization classification. Diagnostic characteristics, treatments, and outcomes
      are described for the entire cohort, for the subgroup of patients with
      translocation-related sarcomas, and for 9 different histologic subtypes. RESULTS:
      The results stressed the magnitude of heterogeneity among adult sarcomas. For
      example, compared with other sarcomas, translocation-related sarcomas (2143
      tumors; 20.8%) were associated with a younger age at presentation (40.6 vs 60.0
      years; P < .0001), a low rate of predisposing conditions (0.01% vs 22.3%; P <
      .0001), a higher rate of lymph node involvement (4.7% vs 1.3%; P < .0001), and a
      higher rate of synchronous metastasis (11.9% vs 6.7%; P < .001); and complete
      (R0) resection (41.6% vs 31.9%; P < .0001), receipt of (neo)adjuvant radiation
      therapy (62.6% vs 42.2%; P < .0001), and receipt of (neo)adjuvant chemotherapy
      (36.6% vs 22.3%; P < .0001) were significantly more frequent. Overall,
      translocation-related sarcomas were associated with a lower rate of local relapse
      (18.1% vs 26.0%; P < .0001) but a higher rate of metastatic relapse (42.0% vs
      30.7%; P < .0001). CONCLUSIONS: Collaborative efforts are urgently needed to
      better assess the natural history and management options for every histologic
      subtype of sarcoma. Cancer 2018;124:1179-87. (c) 2017 American Cancer Society.

PMID- 29211311
TI  - Method and basis set dependence of the NICS indexes of aromaticity for benzene.
AB  - The role of theory level in prediction of benzene magnetic indexes of aromaticity
      is analysed and compared with calculated nuclear magnetic shieldings of 3 He used
      as NMR probe. Three closely related nucleus-independent chemical shift (NICS)
      based indexes were calculated for benzene at SCF-HF, MP2, and DFT levels of
      theory and the impact of basis set on these quantities was studied. The changes
      of benzene NICS(0), NICS(1), and NICS(1)zz parameters calculated using SCF-HF,
      MP2 and several density functionals were within 1 to 3 ppm. Similar deviations
      between magnetic indexes of aromaticity were observed for values calculated with
      selected basis sets. Only very small effect of polar solvent on benzene
      aromaticity was predicted. The 3 He nuclear magnetic isotropic shielding (sigma)
      and its zz-components (sigmazz ) of helium atom approaching the centre of benzene
      ring from above produced similar curves versus benzene-He distance to NICS
      parameters calculated for similarly moving Bq ghost atom. We also propose an
      experimental verification of NICS calculations by designing the 3 He NMR
      measurement for benzene saturated with helium gas or in low temperature matrices.

PMID- 29211312
TI  - Tris(pentafluoroethyl)stannane: Tin Hydride Chemistry with an Electron-Deficient
      Stannane.
AB  - A versatile two-step synthesis of tris(pentafluoroethyl)stannane, HSn(C2 F5 )3 ,
      is presented. Electron-withdrawing C2 F5 groups significantly influence the
      polarity of the tin-hydrogen bond, which allows facile deprotonation of the
      compound, even in water. The utility of this electron-deficient stannane was
      illustrated in hydrostannylations of alkenes and alkynes, as well as in
      dehalogenation reactions. The remarkably high reactivity of HSn(C2 F5 )3 is
      demonstrated in fast hydrostannylations, even in the absence of activators,
      whereby the regioselectivity of this process turns out to be solvent dependent.
      It is of great advantage that in dehalogenation reactions volatile
      halogenotris(pentafluoroethyl)stannanes, XSn(C2 F5 )3 (X=I, Br), are formed that
      allow facile separation of the tin-containing byproducts from the reaction
      mixtures.

PMID- 29211313
TI  - Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine
      carcinomas: A SEER database analysis of 162,983 cases.
AB  - BACKGROUND: Extrapulmonary neuroendocrine carcinomas (NECs) are poorly studied
      and are managed similar to lung NECs, which may not account for differences
      between the 2 groups of tumors as well as the heterogeneity within extrapulmonary
      NEC. METHODS: Data from the Surveillance, Epidemiology, and End Results program
      between 1973 and 2012 were used to estimate the relative percentages of lung NECs
      and subgroups of extrapulmonary NECs, epidemiological patterns at these sites,
      and the median and 5-year overall survival rates. RESULTS: Of 162,983 NEC cases,
      14,732 were extrapulmonary; of these, 5509 were gastrointestinal (37.44%), 4151
      were of unknown primary (28.2%), and 5072 were of other sites (34.4%). Lung NEC
      had the highest percentage of small cell morphology (95.2%) and gastrointestinal
      NEC had the least (38.7%), with the rest being other morphologies. Significant
      differences were noted with regard to median age (range, 48-74 years), percentage
      of cases of distant stage disease (24%-77%), and incidence according to sex and
      race. The median survival of patients with lung NEC was 7.6 months, that for
      patients with gastrointestinal NEC was 7.5 months (range, 25.1 months for NEC at
      the small intestine to 5.7 months for NEC at the pancreas), and that for patients
      with unknown NEC was 2.5 months. The 5-year survival rate for patients with local
      stage disease ranged from 58% to 60% for NECs of the female genital tract and
      small intestine to 25% for esophageal NECs. The primary tumor site remained
      statistically significant for survival even after adjusting for known prognostic
      variables (P<.0001). CONCLUSIONS: To the authors' knowledge, the current study is
      the largest study of NECs performed to date and also the first with comprehensive
      epidemiological data. Significant differences in incidence patterns and large
      variations in survival depending on anatomical site and morphological subtype
      were noted. A curative approach is possible for patients with nonmetastatic NECs.
      Cancer 2018;124:807-15. (c) 2017 American Cancer Society.

PMID- 29211315
TI  - Trends in botanical dietary supplement use among US adults by cancer status: The
      National Health and Nutrition Examination Survey, 1999 to 2014.
AB  - BACKGROUND: Patients with cancer may use botanical dietary supplements (BDS) in
      an attempt to manage the side effects of chemotherapy, yet evidence about BDS use
      among patients with cancer is limited. The authors examined trends in BDS use
      among US adults according to cancer status and patient characteristics. METHODS:
      A serial, cross-sectional study was conducted using data from the National Health
      and Nutrition Examination Survey from 1999 through 2014 (n = 43,644). Self
      reported cancer diagnosis history and any BDS use in the preceding 30 days were
      determined. The prevalence of BDS use was calculated in each cycle for
      respondents with and without cancer, both overall and by patient characteristics.
      Simple linear regression models were applied to test for trends in BDS use at a 2
      sided P value < .05. Multiple logistic regression models were performed to
      identify the patient factors associated with BDS use. The results were weighted
      to represent national estimates. RESULTS: The prevalence of BDS use was greater
      among participants who had cancer compared with participants who did not have
      cancer, but trends remained stable during 1999 through 2014 for both groups.
      Trends in BDS use declined in patients with cancer who were older (Ptrend  =
      .047), had a low annual family income (Ptrend  = .028), and had a lower education
      level (Ptrend  = .004). Among the respondents without cancer, trends in BDS use
      declined in those who were middle-aged (Ptrend  = .025), non-Hispanic whites
      (Ptrend  = .025), those with a lower education level (Ptrend  = .011), and those
      who were not receiving prescription medication (Ptrend  = .036). Patient age,
      sex, race/ethnicity, income, education, and health conditions were associated
      with BDS use. CONCLUSIONS: The overall use of BDS remained stable during 1999
      through 2014 for US adults with and without cancer, but it varied by individual
      characteristics. Cancer 2018;124:1207-15. (c) 2017 American Cancer Society.

PMID- 29211314
TI  - A Highly Enantioselective Copper/Phosphoramidite-Thioether-Catalyzed
      Diastereodivergent 1,3-Dipolar Cycloaddition of Azomethine Ylides and
      Nitroalkenes.
AB  - In contrast to the plethora of catalytic systems that enable access to any
      enantiomers of the chiral products by simply choosing between a pair of
      enantiomeric or pseudoenantiomeric chiral catalysts, few analogously effective
      protocols exist for the synthesis of compounds bearing multiple stereogenic
      centers with full control of the absolute and relative stereochemical
      configurations. Here, we report the application of our previously developed
      modular phosphoramidite-thioether ligands for the copper-catalyzed
      diastereodivergent asymmetric 1,3-dipolar cycloaddition of azomethine ylides and
      nitroalkenes. Our catalytic system enables wide substrate scope, great
      stereochemical control, and high reaction efficiency.

PMID- 29211317
TI  - Neurobiology of gender identity and sexual orientation.
AB  - Sexual identity and sexual orientation are independent components of a person's
      sexual identity. These dimensions are most often in harmony with each other and
      with an individual's genital sex, although not always. The present review
      discusses the relationship of sexual identity and sexual orientation to prenatal
      factors that act to shape the development of the brain and the expression of
      sexual behaviours in animals and humans. One major influence discussed relates to
      organisational effects that the early hormone environment exerts on both gender
      identity and sexual orientation. Evidence that gender identity and sexual
      orientation are masculinised by prenatal exposure to testosterone and feminised
      in it absence is drawn from basic research in animals, correlations of biometric
      indices of androgen exposure and studies of clinical conditions associated with
      disorders in sexual development. There are, however, important exceptions to this
      theory that have yet to be resolved. Family and twin studies indicate that genes
      play a role, although no specific candidate genes have been identified. Evidence
      that relates to the number of older brothers implicates maternal immune responses
      as a contributing factor for male sexual orientation. It remains speculative how
      these influences might relate to each other and interact with postnatal
      socialisation. Nonetheless, despite the many challenges to research in this area,
      existing empirical evidence makes it clear that there is a significant biological
      contribution to the development of an individual's sexual identity and sexual
      orientation.

PMID- 29211316
TI  - The efficacy of prostate-specific antigen screening: Impact of key components in
      the ERSPC and PLCO trials.
AB  - BACKGROUND: The European Randomized Study of Screening for Prostate Cancer
      (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly
      reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval,
      0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated
      no such reduction but had a wide 95% CI (rate ratio for prostate cancer
      mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account
      for key differences between the trials that can impact the estimated effects of
      screening and the trials' point estimates. METHODS: The authors calibrated 2
      microsimulation models to individual-level incidence and mortality data from
      238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the
      underlying efficacy of screening was estimated by the models separately for each
      trial. The authors changed step-by-step major known differences in trial
      settings, including enrollment and attendance patterns, screening intervals, PSA
      thresholds, biopsy receipt, control arm contamination, and primary treatment, to
      reflect a more ideal protocol situation and differences between the trials.
      RESULTS: Using the cure parameter estimated for the ERSPC, the models projected
      19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in
      the ERSPC and PLCO settings. Using this cure parameter, the models projected a
      reduction of 37% to 43% under annual screening with 100% attendance and biopsy
      compliance and no contamination. The cure parameter estimated for the PLCO trial
      was 0. CONCLUSIONS: The observed cancer mortality reduction in screening trials
      appears to be highly sensitive to trial protocol and practice settings.
      Accounting for these differences, the efficacy of PSA screening in the PLCO
      setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197
      206. (c) 2017 American Cancer Society.

PMID- 29211318
TI  - Nitrogen-rich microbial products provide new organo-mineral associations for the
      stabilization of soil organic matter.
AB  - Understanding the cycling of C and N in soils is important for maintaining soil
      fertility while also decreasing greenhouse gas emissions, but much remains
      unknown about how organic matter (OM) is stabilized in soils. We used nano-scale
      secondary ion mass spectrometry (NanoSIMS) to investigate the changes in C and N
      in a Vertisol and an Alfisol incubated for 365 days with 13 C and 15 N pulse
      labeled lucerne (Medicago sativa L.) to discriminate new inputs of OM from the
      existing soil OM. We found that almost all OM within the free stable
      microaggregates of the soil was associated with mineral particles, emphasizing
      the importance of organo-mineral interactions for the stabilization of C. Of
      particular importance, it was also found that 15 N-rich microbial products
      originating from decomposition often sorbed directly to mineral surfaces not
      previously associated with OM. Thus, we have shown that N-rich microbial products
      preferentially attach to distinct areas of mineral surfaces compared to C
      dominated moieties, demonstrating the ability of soils to store additional OM in
      newly formed organo-mineral associations on previously OM-free mineral surfaces.
      Furthermore, differences in 15 N enrichment were observed between the Vertisol
      and Alfisol presumably due to differences in mineralogy (smectite-dominated
      compared to kaolinite-dominated), demonstrating the importance of mineralogy in
      regulating the sorption of microbial products. Overall, our findings have
      important implications for the fundamental understanding of OM cycling in soils,
      including the immobilization and storage of N-rich compounds derived from
      microbial decomposition and subsequent N mineralization to sustain plant growth.

PMID- 29211321
TI  - Recovery Mechanism of Degraded Black Phosphorus Field-Effect Transistors by 1,2
      Ethanedithiol Chemistry and Extended Device Stability.
AB  - Black phosphorus (BP) has drawn enormous attention for both intriguing material
      characteristics and electronic and optoelectronic applications. In spite of
      excellent advantages for semiconductor device applications, the performance of BP
      devices is hampered by the formation of phosphorus oxide on the BP surface under
      ambient conditions. It is thus necessary to resolve the oxygen-induced
      degradation on the surface of BP to recover the characteristics and stability of
      the devices. To solve this problem, it is demonstrated that a 1,2-ethanedithiol
      (EDT) treatment is a simple and effective way to remove the bubbles formed on the
      BP surface. The device characteristics of the degraded BP field-effect transistor
      (FET) are completely recovered to the level of the pristine cases by the EDT
      treatment. The underlying principle of bubble elimination on the BP surface by
      the EDT treatment is systematically analyzed by density functional theory
      calculation, atomic force microscopy, and X-ray photoelectron spectroscopy
      analysis. In addition, the performance of the hexagonal boron nitride-protected
      BP FET is completely retained without changing device characteristics even when
      exposed to 30 d or more in air. The EDT-induced recovering effect will allow a
      new route for the optimization of electronic and optoelectronic devices based on
      BP.

PMID- 29211320
TI  - Consensus statements on the management of metastatic prostate cancer from the
      Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.
AB  - To establish a set of consensus statements to facilitate physician management
      strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A
      local expert consensus was organized jointly by the two main professional
      organizations representing prostate cancer specialists in Hong Kong. A total of
      12 experts were included in the consensus panel. Six of the most crucial and
      relevant areas of debate regarding the management of mPCa were identified. With
      the use of a modified Delphi method, several panel meetings were held for the
      members to discuss their clinical experience and the published literature
      relevant to the areas of debate. At the final meeting, each drafted statement was
      voted on by every member based on its practicability of recommendation in the
      locality. After the panel voting, a total of 45 consensus statements regarding
      the management of mPCa were ultimately accepted and established. The consensus
      statements were primarily derived from the latest clinical evidence and major
      overseas guidelines, with the consideration of local clinical experience and
      practicability. These are considered applicable recommendations for Hong Kong
      physicians for the management of mPCa patients.

PMID- 29211322
TI  - Perivascular adipose tissue and the dynamic regulation of Kv 7 and Kir channels:
      Implications for resistant hypertension.
AB  - Resistant hypertension is defined as high blood pressure that remains
      uncontrolled despite treatment with at least three antihypertensive drugs at
      adequate doses. Resistant hypertension is an increasingly common clinical problem
      in older age, obesity, diabetes, sleep apnea, and chronic kidney disease.
      Although the direct vasodilator minoxidil was introduced in the early 1970s, only
      recently has this drug been shown to be particularly effective in a subgroup of
      patients with treatment-resistant or uncontrolled hypertension. This
      pharmacological approach is interesting from a mechanistic perspective as
      minoxidil is the only clinically used K+ channel opener today, which targets a
      subclass of K+ channels, namely KATP channels in VSMCs. Beside KATP channels, two
      other classes of VSMC K+ channels could represent novel effective targets for
      treatment of resistant hypertension, namely Kv 7 (KCNQ) and inward rectifier
      potassium (Kir 2.1) channels. Interestingly, these channels are unique among VSMC
      potassium channels. First, both have been implicated in the control of
      microvascular tone by perivascular adipose tissue. Second, they exhibit
      biophysical properties strongly controlled and regulated by membrane voltage, but
      not intracellular calcium. This review focuses on Kv 7 (Kv 7.1-5) and Kir (Kir
      2.1) channels in VSMCs as potential novel drug targets for treatment of resistant
      hypertension, particularly in comorbid conditions such as obesity and metabolic
      syndrome.

PMID- 29211323
TI  - Medical applications of nonthermal atmospheric pressure plasma in dermatology.
AB  - Plasma is an ionized gas that consists of positively and negatively charged
      particles, neutral atoms, and photons. Recent developments in plasma sources have
      made it possible to generate room-temperature plasma in the "open air", thus
      enabling the application of plasma in vivo. Using nonthermal plasma, active
      agents can be efficiently delivered to target cells without creating thermal
      damage. Also known as cold atmospheric pressure plasma (CAP), nonthermal
      atmospheric pressure plasma offers innovative medical applications. In this
      context, it has also gained wide attention in the field of dermatology. The
      complex and variable mixture of active agents in plasma - predominantly reactive
      oxygen and nitrogen species (ROS, RNS) - can control or trigger complex
      biochemical reactions, achieving the desired effects in a dose-dependent manner.
      The objective of the present review is to present potential applications of
      plasma in dermatology and analyze its potential mechanisms of action.

PMID- 29211319
TI  - Clinical implications of bone marrow adiposity.
AB  - Marrow adipocytes, collectively termed marrow adipose tissue (MAT), reside in the
      bone marrow in close contact to bone cells and haematopoietic cells. Marrow
      adipocytes arise from the mesenchymal stem cell and share their origin with the
      osteoblast. Shifts in the lineage allocation of the mesenchymal stromal cell
      could potentially explain the association between increased MAT and increased
      fracture risk in diseases such as postmenopausal osteoporosis, anorexia nervosa
      and diabetes. Functionally, marrow adipocytes secrete adipokines, such as
      adiponectin, and cytokines, such as RANK ligand and stem cell factor. These
      mediators can influence both bone remodelling and haematopoiesis by promoting
      bone resorption and haematopoietic recovery following chemotherapy. In addition,
      marrow adipocytes can secrete free fatty acids, acting as a energy supply for
      bone and haematopoietic cells. However, this induced lipolysis is also used by
      neoplastic cells to promote survival and proliferation. Therefore, MAT could
      represent a new therapeutic target for multiple diseases from osteoporosis to
      leukaemia, although the exact characteristics and role of the marrow adipocyte in
      health and diseases remain to be determined.

PMID- 29211324
TI  - Non-invasive prenatal testing for fetal inheritance of maternal beta-thalassaemia
      mutations using targeted sequencing and relative mutation dosage: a feasibility
      study.
AB  - OBJECTIVE: To evaluate whether targeted sequencing and relative mutation dosage
      can be used to diagnose correctly inheritance of maternal beta-thalassaemia
      mutations in cell-free DNA. DESIGN: Feasibility study using samples collected in
      a prenatal clinic. SETTING: South East Asia. POPULATION: Couples where both
      partners were known to be carriers of one of four common beta-thalassaemia
      mutations or an HbE mutation, and therefore at risk of carrying a fetus affected
      with beta-thalassaemia. METHODS: 49 samples previously identified as having
      inherited a paternal beta-thalassaemia mutation were amplified using nested
      polymerase chain reaction (PCR), and then sequencing. Relative mutation dosage
      was used to classify the fetus as having inherited the wild-type or mutant
      maternal allele. MAIN OUTCOME MEASURES: Classification of the fetus as
      'unaffected' (if the maternal wild-type allele was inherited) or 'affected' with
      beta-thalassaemia (if the maternal mutant allele was inherited). RESULTS: A
      classification for inheritance of maternal allele was obtained in 48/49 samples
      (98.0%). A concordant call was made in 44/48 cases (91.7%): one false-positive
      and three false-negatives were obtained. Thus, we had an overall sensitivity of
      87.5% [95% confidence interval (CI) 67.6-97.3%] and a specificity of 95.8% (95%
      CI 78.9-99.9%) for inheritance of maternal genotype. CONCLUSIONS: RMD for
      detection of inheritance of maternal beta-thalassaemia mutations has potential
      for clinical use. Our sequential approach could be applied to other single-gene
      disorders. TWEETABLE ABSTRACT: NIPT for beta-thalassaemia achieved using nested
      PCR followed by relative mutation dosage.

PMID- 29211326
TI  - Recent work supports the concept of an active sphincter in the uterine cervix.

PMID- 29211325
TI  - Climate change leads to differential shifts in the timing of annual cycle stages
      in a migratory bird.
AB  - Shifts in reproductive phenology due to climate change have been well documented
      in many species but how, within the same species, other annual cycle stages (e.g.
      moult, migration) shift relative to the timing of breeding has rarely been
      studied. When stages shift at different rates, the interval between stages may
      change resulting in overlaps, and as each stage is energetically demanding, these
      overlaps may have negative fitness consequences. We used long-term data of a
      population of European pied flycatchers (Ficedula hypoleuca) to investigate
      phenological shifts in three annual cycle stages: spring migration (arrival
      dates), breeding (egg-laying and hatching dates) and the onset of postbreeding
      moult. We found different advancements in the timing of breeding compared with
      moult (moult advances faster) and no advancement in arrival dates. To understand
      these differential shifts, we explored which temperatures best explain the year
      to-year variation in the timing of these stages, and show that they respond
      differently to temperature increases in the Netherlands, causing the intervals
      between arrival and breeding and between breeding and moult to decrease. Next, we
      tested the fitness consequences of these shortened intervals. We found no effect
      on clutch size, but the probability of a fledged chick to recruit increased with
      a shorter arrival-breeding interval (earlier breeding). Finally, mark-recapture
      analyses did not detect an effect of shortened intervals on adult survival. Our
      results suggest that the advancement of breeding allows more time for fledgling
      development, increasing their probability to recruit. This may incur costs to
      other parts of the annual cycle, but, despite the shorter intervals, there was no
      effect on adult survival. Our results show that to fully understand the
      consequences of climate change, it is necessary to look carefully at different
      annual cycle stages, especially for organisms with complex cycles, such as
      migratory birds.

PMID- 29211327
TI  - Combined abdomino-sacral laparoscopically assisted approach for retrorectal mass
      resection in a patient with Currarino's Syndrome - video vignette.
AB  - A correct preoperative strategy is crucial when surgery is needed for retrorectal
      tumours (RRT).[1] Surgical approaches may be purely anterior-abdominal, posterior
      sacrococcygeal or combined depending on the tumour's size and location.[2] We
      present the case of an 18-year-old female with Currarino Syndrome who underwent
      surgery by a combined abdominal laparoscopic-posterior Kraske approach for the
      resection of a large RRT. This article is protected by copyright. All rights
      reserved.

PMID- 29211328
TI  - Safety of the balloon catheter for cervical ripening in outpatient care:
      complications during the period from insertion to expulsion of a balloon catheter
      in the process of labour induction: a systematic review.
AB  - BACKGROUND: It has been suggested that cervical ripening with a balloon catheter
      for labour induction can be done in an outpatient setting in low-risk
      pregnancies. Introduction of such an approach needs to be accompanied with
      monitoring of potential complications. Therefore the existence and frequency of
      any associated adverse event during cervical ripening needs to be established.
      OBJECTIVE: To assess the complication rate during cervical ripening with balloon
      induction. SEARCH STRATEGY: We searched Embase, Medline, Cochrane Collaboration
      and CINAHL using keywords 'induction of labour', 'cervical ripening', 'balloon
      catheter', 'Foley balloon', 'transcervical balloon'. SELECTION CRITERIA: We
      included randomized controlled trials and cohort studies containing original data
      on fetal and maternal morbidity in pregnant women during cervical ripening with a
      balloon catheter. Only articles for which authors were able to give data for this
      exact time frame were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      assessed independently the eligibility of included studies, extracted data and
      performed a quality assessment. A meta-analysis was performed to calculate the
      estimated prevalence of the adverse events. MAIN RESULTS: In total 26 studies
      were included reporting on 8292 women. The estimated prevalence of the analysed
      adverse events in the random effects model was between 0.0 and 0.26%, of which
      'pain/discomfort' had the highest prevalence. CONCLUSION: This study suggests the
      risk of adverse events during the period between insertion and expulsion of a
      balloon catheter in cervical ripening to be low. These data facilitate further
      evaluation and implementation of this procedure in an outpatient setting for low
      risk pregnancies. TWEETABLE ABSTRACT: Balloon catheter for cervical ripening
      appears to be safe enough to evaluate its use in the outpatient setting.

PMID- 29211329
TI  - Visible-Light Emulsion Photopolymerization of Styrene.
AB  - The photopolymerization of styrene in emulsion is achieved in a conventional
      double-wall reactor equipped with a LED ribbon coiled around the external glass
      wall. Styrene mixed to acridine orange is added to the water phase containing
      sodium dodecyl sulfate, a water-soluble N-heterocyclic carbene-borane and
      disulfide, and irradiated. Highly stable latexes are obtained, with particles up
      to a diameter of 300 nm. The ability to reach such large particle sizes via a
      photochemical process in a dispersed medium is due to the use of visible light:
      the photons in the visible range are less scattered by larger objects and thus
      penetrate and initiate better the polymerizations. They are also greener and
      cheaper to produce via LEDs, and much safer than UVs. The method presented does
      not require any specific glassware; it works at lower temperature and delivers
      larger particles compared to thermal processes at similar solids contents and
      surfactant concentrations.

PMID- 29211330
TI  - Cross-Coupling of Sodium Sulfinates with Aryl, Heteroaryl, and Vinyl Halides by
      Nickel/Photoredox Dual Catalysis.
AB  - An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl,
      heteroaryl, and vinyl halides has been achieved for the first time. This newly
      developed sulfonylation protocol provides a versatile method for the synthesis of
      diverse aromatic sulfones at room temperature and shows excellent functional
      group tolerance. The electrophilic coupling partners are not limited to aryl,
      heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl
      chlorides as suitable substrates for this transformation.

PMID- 29211331
TI  - Fabrication of Defined Polydopamine Nanostructures by DNA Origami-Templated
      Polymerization.
AB  - A versatile, bottom-up approach allows the controlled fabrication of polydopamine
      (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been
      investigated as an adhesive and promising surface coating material. However, the
      control of dopamine polymerization is challenged by the multistage-mediated
      reaction mechanism and diverse chemical structures in PD. DNA origami decorated
      with multiple horseradish peroxidase-mimicking DNAzyme motifs was used to control
      the shape and size of PD formation with nanometer resolution. These fabricated PD
      nanostructures can serve as "supramolecular glue" for controlling DNA origami
      conformations. Facile liberation of the PD nanostructures from the DNA origami
      templates has been achieved in acidic medium. This presented DNA origami
      controlled polymerization of a highly crosslinked polymer provides a unique
      access towards anisotropic PD architectures with distinct shapes that were
      retained even in the absence of the DNA origami template.

PMID- 29211332
TI  - Incidental detection of new-onset melanoma using PET-CT in a patient with stage
      III melanoma.

PMID- 29211333
TI  - Subsequent reproductive outcome among women with peripartum cardiomyopathy: a
      nationwide study.
AB  - OBJECTIVE: To describe the subsequent reproductive outcome for a Danish
      nationwide cohort of women with peripartum cardiomyopathy (PPCM). DESIGN:
      Nationwide historic cohort study. SETTING: Secondary and tertiary centres across
      Denmark. SAMPLE: Women with PPCM. METHODS: Sixty-one women with PPCM during 2005
      2014 were identified in a nationwide, registry-based study and the diagnosis was
      validated through audit of patient records. A new search for subsequent
      reproductive outcome in this cohort from 2005-2016 was conducted in the Danish
      National Birth Registry and the Danish National Patient Registry. Detailed
      clinical data were obtained from patient records. MAIN OUTCOME MEASURES:
      Sterilisations and subsequent reproductive outcomes after PPCM, including all
      pregnancies, miscarriages, terminations and deliveries. RESULTS: Of 61 women with
      PPCM, 13 (21%) had a total of 16 subsequent pregnancies resulting in one
      miscarriage, seven early terminations, one ectopic pregnancy and seven liveborn
      children. There were no maternal deaths or significant cardiac events during
      pregnancy, but one woman, who gave birth to a liveborn child, had a relapse of
      PPCM 7 weeks postpartum. None of the six women who had a first trimester
      termination, experienced relapse of PPCM. Of the 13 women with a subsequent
      pregnancy, 62% had prior to this been advised against a new pregnancy due to the
      risk of recurrent PPCM. A total of four women (6.6%) were sterilised. CONCLUSION:
      Peripartum cardiomyopathy affects women's reproduction with few subsequent
      pregnancies resulting in a liveborn child. The finding of a 1/7 relapse among
      women with recovered LVEF is in accordance with most previous studies. TWEETABLE
      ABSTRACT: Outcome in pregnancies after peripartum cardiomyopathy: results from
      the first nationwide study.

PMID- 29211334
TI  - Perichondritis of the ear in an Afghan immigrant.

PMID- 29211335
TI  - Lichen planus-like drug eruption on anti-PD-1 therapy.

PMID- 29211337
TI  - Occupational Darier's disease.

PMID- 29211336
TI  - Diverse effects of invasive ecosystem engineers on marine biodiversity and
      ecosystem functions: A global review and meta-analysis.
AB  - Invasive ecosystem engineers (IEE) are potentially one of the most influential
      types of biological invaders. They are expected to have extensive ecological
      impacts by altering the physical-chemical structure of ecosystems, thereby
      changing the rules of existence for a broad range of resident biota. To test the
      generality of this expectation, we used a global systematic review and meta
      analysis to examine IEE effects on the abundance of individual species and
      communities, biodiversity (using several indices) and ecosystem functions,
      focusing on marine and estuarine environments. We found that IEE had a
      significant effect (positive and negative) in most studies testing impacts on
      individual species, but the overall (cumulative) effect size was small and
      negative. Many individual studies showed strong IEE effects on community
      abundance and diversity, but the direction of effects was variable, leading to
      statistically non-significant overall effects in most categories. In contrast,
      there was a strong overall effect on most ecosystem functions we examined. IEE
      negatively affected metabolic functions and primary production, but positively
      affected nutrient flux, sedimentation and decomposition. We use the results to
      develop a conceptual model by highlighting pathways whereby IEE impact
      communities and ecosystem functions, and identify several sources of research
      bias in the IEE-related invasion literature. Only a few of the studies
      simultaneously quantified IEE effects on community/diversity and ecosystem
      functions. Therefore, understanding how IEE may alter biodiversity-ecosystem
      function relationships should be a primary focus of future studies of invasion
      biology. Moreover, the clear effects of IEE on ecosystem functions detected in
      our study suggest that scientists and environmental managers ought to examine how
      the effects of IEE might be manifested in the services that marine ecosystems
      provide to humans.

PMID- 29211338
TI  - Look, then leap: quality and improving maternity care.

PMID- 29211339
TI  - beta3-adrenoceptor agonists inhibit carbachol-evoked Ca2+ oscillations in murine
      detrusor myocytes.
AB  - OBJECTIVE: To test if carbachol (CCh)-evoked Ca2+ oscillations in freshly
      isolated murine detrusor myocytes are affected by beta3-adrenoceptor (beta-AR)
      modulators. MATERIALS AND METHODS: Isometric tension recordings were made from
      strips of murine detrusor, and intracellular Ca2+ measurements were made from
      isolated detrusor myocytes using confocal microscopy. Transcriptional expression
      of beta-AR sub-types in detrusor strips and isolated detrusor myocytes was
      assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and real
      time quantitative PCR (qPCR). Immunocytochemistry experiments, using a beta3-AR
      selective antibody, were performed to confirm that beta3-ARs were present on
      detrusor myocytes. RESULTS: The RT-PCR and qPCR experiments showed that beta1-,
      beta2- and beta3-AR were expressed in murine detrusor, but that beta3-ARs were
      the most abundant sub-type. The selective beta3-AR agonist BRL37344 reduced the
      amplitude of CCh-induced contractions of detrusor smooth muscle. These responses
      were unaffected by addition of the BK channel blocker iberiotoxin. BRL37344 also
      reduced the amplitude of CCh-induced Ca2+ oscillations in freshly isolated murine
      detrusor myocytes. This effect was mimicked by CL316,243, another beta3-AR
      agonist, and inhibited by the beta3-AR antagonist L748,337, but not by
      propranolol, an antagonist of beta1- and beta2-ARs. BRL37344 did not affect
      caffeine-evoked Ca2+ transients or L-type Ca2+ current in isolated detrusor
      myocytes. CONCLUSION: Inhibition of cholinergic-mediated contractions of the
      detrusor by beta3-AR agonists was associated with a reduction in Ca2+
      oscillations in detrusor myocytes.

PMID- 29211340
TI  - Treatment-recalcitrant comedones.

PMID- 29211341
TI  - Chiral separation of lenalidomide by liquid chromatography on polysaccharide-type
      stationary phases and by capillary electrophoresis using cyclodextrin selectors.
AB  - Complementary techniques were applied for the investigation of the chiral
      recognition and enantiomeric resolution of lenalidomide using various
      cyclodextrins and polysaccharides as chiral selectors. The high-performance
      liquid chromatography enantioseparation of the anticancer drug was achieved using
      polysaccharide-type chiral stationary phases in polar organic mode. Elution order
      and absolute configuration were elucidated by combined circular dichroism
      spectroscopy and time-dependent density functional theory calculations after the
      isolation of pure enantiomers. Chiral selector dependent and mobile-phase
      dependent reversal of the enantiomer elution order was observed, and the
      nonracemic nature of the lenalidomide sample was also demonstrated. Eight anionic
      cyclodextrins were screened for their ability to discriminate between the
      uncharged enantiomers by using capillary electrophoresis. Only two derivatives
      presented chiral interactions, these cases being interpreted in terms of apparent
      stability constants and complex mobilities. The best results were delivered by
      sulfobutylether-beta-cyclodextrin, where quasi-equal stability constants were
      recorded and the enantiodiscrimination process was mainly driven by different
      mobilities of the transient diastereomeric complexes. The optimized high
      performance liquid chromatography (Chiralcel OJ column, pure ethanol with 0.6
      mL/min flow rate, 40 degrees C) and capillary electrophoresis methods (30 mM
      sulfobutylether-beta-cyclodextrin, 30 mM phosphate pH 6.5, 12 kV applied voltage,
      10 degrees C) were validated for the determination of 0.1% (R)-lenalidomide as a
      chiral impurity, which could be important if a racemic switch is achieved.

PMID- 29211342
TI  - Functional BKCa channel in human resident cardiac stem cells expressing W8B2.
AB  - Recently, a new population of resident cardiac stem cells (CSCs) positive for the
      W8B2 marker has been identified. These CSCs are considered to be an ideal
      cellular source to repair myocardial damage after infarction. However, the
      electrophysiological profile of these cells has not been characterized yet. We
      first establish the conditions of isolation and expansion of W8B2+ CSCs from
      human heart biopsies using a magnetic sorting system followed by flow cytometry
      cell sorting. These cells display a spindle-shaped morphology, are highly
      proliferative, and possess self-renewal capacity demonstrated by their ability to
      form colonies. Besides, W8B2+ CSCs are positive for mesenchymal markers but
      negative for hematopoietic and endothelial ones. RT-qPCR and immunostaining
      experiments show that W8B2+ CSCs express some early cardiac-specific
      transcription factors but lack the expression of cardiac-specific structural
      genes. Using patch clamp in the whole-cell configuration, we show for the first
      time the electrophysiological signature of BKCa current in these cells.
      Accordingly, RT-PCR and western blotting analysis confirmed the presence of BKCa
      at both mRNA and protein levels in W8B2+ CSCs. Interestingly, BKCa channel
      inhibition by paxilline decreased cell proliferation in a concentration-dependent
      manner and halted cell cycle progression at the G0/G1 phase. The inhibition of
      BKCa also decreased the self-renewal capacity but did not affect migration of
      W8B2+ CSCs. Taken together, our results are consistent with an important role of
      BKCa channels in cell cycle progression and self-renewal in human cardiac stem
      cells.

PMID- 29211343
TI  - Exploring Structure-Activity Relationships with Three-Dimensional Matched
      Molecular Pairs-A Review.
AB  - A matched molecular pair (MMP) consists of two small molecules that differ by a
      few atoms only. The minor structural difference between the molecules allows a
      detailed analysis of changes in properties. Three-dimensional (3D) MMPs extend
      the concept of chemical similarity by spatial similarity. Conformations must be
      generated, and superimpositions have to be calculated. The additional complexity
      and uncertainty as well as the smaller amount of available experimental data
      substantially complicates the derivation of models. Nonetheless, there are some
      benefits that make the transition worthwhile. The 3D concept gives detailed
      insight into mechanisms behind several methods classically used by the 2D MMP
      approach. It can help to analyze disrupted series of structure-activity
      relationships or extend the 2D MMP concept with scaffold hopping. One of the most
      powerful features is the high confidence structure-activity relationship transfer
      between series of analogues. Several research groups have approached the problem
      from different directions. The models vary especially in the 3D similarity
      measure used and complexity of the applied descriptor selected or designed.
      Nonetheless, all approaches have increased the amount of information available by
      incorporating 3D structural information.

PMID- 29211344
TI  - Preparation of silica microspheres with a broad pore size distribution and their
      use as the support for a coated cellulose derivative chiral stationary phase.
AB  - A templating strategy using crosslinked and functionalized polymeric beads to
      synthesize silica microspheres with a broad pore size distribution has been
      developed. The polymer/silica hybrid microspheres were prepared by utilizing the
      combination of a templating weak cation exchange resin, a structure-directing
      agent N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride, and a silica
      precursor tetraethyl orthosilicate. The silica microspheres were then obtained
      after calcinating the hybrid microspheres. The as-prepared materials were
      characterized by scanning electron microscopy, mercury intrusion porosimeter, and
      thermal gravimetric analysis. The results showed that the starting templating
      beads were about 5 MUm in diameter and the formed silica microspheres were less
      than 3 MUm with a pore size range of 10-150 nm, some pores were even extended to
      beyond 250 nm. It was demonstrated that cellulose tris(3,5
      dimethylphenylcarbamate) was readily coated onto the surface of the as
      synthesized silica microspheres without any additional surface pretreatment. The
      coated silica microspheres were uniformly dispersed even with high loading of the
      chiral stationary phase, which exhibited high resolution chiral separations in
      high-performance liquid chromatography.

PMID- 29211345
TI  - pH-Responsive Polyacetal-Protein Conjugates Designed for Polymer Masked-Unmasked
      Protein Therapy (PUMPT).
AB  - Polymer masked-unmasked protein therapy (PUMPT) employs polymer conjugation to
      protect therapeutic proteins during transit through the bloodstream and allow
      controlled release at a disease site via triggered degradation of the polymeric
      component. Most reported PUMPT systems are based on the specific enzymatic
      degradation of the polymeric component to release the protein and reinstate its
      activity. In these cases, therapeutic output is dependent on the presence of the
      required enzyme at the disease site at a sufficiently high concentration. The
      present study aims to overcome this design limitation by using pH as the protein
      release trigger. An acidic-pH triggered PUMPT system is described herein
      employing biodegradable polyacetals (PAs) and trypsin as a model protein. While
      this system protects trypsin activity at the neutral pH of the bloodstream,
      acidic pH (characteristic of disease sites, tissue damage, or lysosomal
      compartments) contributes to PA degradation and the "unmasking" of protein
      activity.

PMID- 29211346
TI  - Chemogenomic Active Learning's Domain of Applicability on Small, Sparse qHTS
      Matrices: A Study Using Cytochrome P450 and Nuclear Hormone Receptor Families.
AB  - Computational models for predicting the activity of small molecules against
      targets are now routinely developed and used in academia and industry, partially
      due to public bioactivity databases. While models based on bigger datasets are
      the trend, recent studies such as chemogenomic active learning have shown that
      only a fraction of data is needed for effective models in many cases. In this
      article, the chemogenomic active learning method is discussed and used to newly
      analyze public databases containing nuclear hormone receptor and cytochrome P450
      enzyme family bioactivity. In addition to existing results on kinases and G
      protein coupled receptors, results here demonstrate the active learning
      methodology's effectiveness on extracting informative ligand-target pairs in
      sparse data scenarios. Experiments to assess the domain of the applicability
      demonstrate the influence of ligand profiles of similar targets within the
      family.

PMID- 29211347
TI  - Long-term viral suppression and immune recovery during first-line antiretroviral
      therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.
AB  - INTRODUCTION: Achieving viral suppression is key in the global strategy to end
      the HIV epidemic. However, the levels of viral suppression have yet to be
      described in many resource-limited settings. METHODS: We investigated the time to
      virologic failure (VF; defined as a viral load of >=1000 copies/ml) and changes
      in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV
      infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired
      early immune recovery (defined as not attaining an increase in 100 cells/mm3 in
      CD4 counts at 24 months) were further analysed. RESULTS: From 1806 participants,
      225 were identified as having VF at a median of 50 months of first-line ART. The
      viral suppression rate at 12 months was 95.5% and survival without VF was
      maintained above 90% until 42 months. An increase in CD4 counts from the baseline
      was greater in groups with lower baseline CD4 counts. A younger age (multivariate
      hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR
      1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT))
      were associated with earlier VF. Factors associated with impaired early immune
      recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity
      (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens
      (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. CONCLUSION:
      Durable high-rate viral suppression was observed in the cohort of patients on
      first-line ART in Vietnam. Our results highlight the need to increase adherence
      support among injection drug users and HCV co-infected patients.

PMID- 29211348
TI  - 14-3-3 proteins mediate inhibitory effects of cAMP on salt-inducible kinases
      (SIKs).
AB  - The salt-inducible kinase (SIK) family regulates cellular gene expression via the
      phosphorylation of cAMP-regulated transcriptional coactivators (CRTCs) and class
      IIA histone deacetylases, which are sequestered in the cytoplasm by
      phosphorylation-dependent 14-3-3 interactions. SIK activity toward these
      substrates is inhibited by increases in cAMP signaling, although the underlying
      mechanism is unclear. Here, we show that the protein kinase A (PKA)-dependent
      phosphorylation of SIKs inhibits their catalytic activity by inducing 14-3-3
      protein binding. SIK1 and SIK3 contain two functional PKA/14-3-3 sites, while
      SIK2 has four. In keeping with the dimeric nature of 14-3-3s, the presence of
      multiple binding sites within target proteins dramatically increases binding
      affinity. As a result, loss of a single 14-3-3-binding site in SIK1 and SIK3
      abolished 14-3-3 association and rendered them insensitive to cAMP. In contrast,
      mutation of three sites in SIK2 was necessary to fully block cAMP regulation.
      Superimposed on the effects of PKA phosphorylation and 14-3-3 association, an
      evolutionary conserved domain in SIK1 and SIK2 (the so called RK-rich region; 595
      624 in hSIK2) is also required for the inhibition of SIK2 activity. Collectively,
      these results point to a dual role for 14-3-3 proteins in repressing a family of
      Ser/Thr kinases as well as their substrates.

PMID- 29211349
TI  - Evaluation of the cytotoxicity of selected conventional glass ionomer cements on
      human gingival fibroblasts.
AB  - BACKGROUND: Dentistry materials are the most frequently used substitutes of human
      tissues. Therefore, an assessment of dental filling materials should cover not
      only their chemical, physical, and mechanical characteristics, but also their
      cytotoxicity. OBJECTIVES: To compare the cytotoxic effects of 13 conventional
      glass ionomer cements on human gingival fibroblasts. MATERIAL AND METHODS: The
      assessment was conducted using the MTT test. Six samples were prepared for each
      material. Culture plates with cells and inserts with the materials were incubated
      at 37 degrees C, 5% CO2, and 95% humidity for 24 h. Then the inserts were
      removed, 1 mL of MTT was added in the amount of 0.5 mg/1 mL of the medium, and
      the samples were incubated in the described conditions without light for 2 h. The
      optical density was measured with an absorption spectrophotometer at a wavelength
      of 560 nm. RESULTS: The cytotoxic effects of the Argion Molar was significantly
      stronger than the Fuji Triage (p = 0.007), Chemfil Molar (p < 0.0001), and
      Ionofil Molar AC Quick (p < 0.001). The Fuji IX GP and Fuji IX Extra had a
      significantly stronger adverse effect than the Chemfil Molar (p = 0.014, p =
      0.029, respectively) and Ionofil Molar AC Quick (p = 0.017, p = 0.034,
      respectively). The cements from the low cytotoxicity group were significantly
      more toxic vs materials whose presence resulted in fibroblast growth (p < 0.001).
      CONCLUSIONS: The research conducted indicates that, although the materials
      studied may belong to the same group, they are characterized by low, yet not
      uniform, cytotoxicity on human gingival fibroblasts. The toxic effects should not
      be assigned to a relevant group of materials, but each dentistry product should
      be evaluated individually.

PMID- 29211350
TI  - The angiotensin II receptors type 1 blockage affects the urinary bladder activity
      in hyperosmolar-induced detrusor overactivity in rats: Preliminary results.
AB  - BACKGROUND: Angiotensin II receptors play a role in the pathogenesis of urinary
      bladder dysfunction, especially in the case of bladder outlet obstruction. The
      function of these receptors in the detrusor overactivity (DO) still remains
      unclear. OBJECTIVES: The study aims to investigate some of the mechanisms through
      which hyperosmolarity induces urinary bladder overactivity. The effect of
      angiotensin II receptor type 1 - AT1 (telmisartan) on urinary bladder function in
      physiological state and in hyperosmolar-induced DO in rat model was explored.
      MATERIAL AND METHODS: Experiments were performed on 32 female Wistar rats. DO was
      induced by hyperosmolar saline intravesical instillation. Surgical procedures and
      cystometry were performed under urethane anesthesia. The measurements represent
      the average of 5 bladder micturition cycles. We analyzed: basal pressure,
      threshold pressure, micturition voiding pressure, intercontraction interval,
      compliance, functional bladder capacity, motility index and detrusor overactivity
      index. RESULTS: Intravesical hyperosmolar saline instillation induced DO.
      Telmisartan diminished the severity of hyperosmolar-induced DO. We observed a
      statistically significant increase of intercontraction interval (55%), functional
      bladder capacity (54%), compliance (140%). Also, a statistically significant
      decrease of detrusor overactivity index (18%) and motility index (9%) were
      observed. The difference of basal pressure, threshold pressure and micturition
      voiding pressure were not statistically significant. Moreover, telmisartan has no
      effect on urodynamic parameters in naive rats. CONCLUSIONS: Detrusor overactivity
      due to intravesical increased osmolarity seems to be at least partially mediated
      by AT1 receptors activity. On one hand, telmisartan diminished the severity of
      hyperosmolarinduced DO, and, on the other hand, has no effect on urodynamic
      parameters in naive rats.

PMID- 29211351
TI  - Application of Fourier transform infrared spectroscopy to biomolecular profiling
      of cultured fibroblast cells from Gaucher disease patients: A preliminary
      investigation.
AB  - BACKGROUND: Gaucher disease (GD) is defined as an autosomal recessive disorder
      resulting from the deficiency of glucocerebrosidase (E.C. 3.2.1.45).
      Glucocerebrosidase is responsible for the degradation of glucosylceramide into
      ceramide and glucose. The deficiency of this enzyme results in the accumulation
      of undegraded glucosylceramide, almost exclusively in macrophages. With Fourier
      transform infrared (FTIR) spectroscopy, the complete molecular diversity of the
      samples can be studied comparatively and the amount of the particular materials
      can be determined. Also, the secondary structure ratios of proteins can be
      determined by analysing the amide peaks. OBJECTIVES: The primary aim of this
      study is to introduce FTIR-ATR spectroscopy technique to GD research for the
      first time in the literature and to assess its potential as a new molecular
      method. MATERIAL AND METHODS: Primary fibroblast cell cultures obtained from
      biopsy samples were used, since this material is widely used for the diagnosis of
      GD. Intact cells were placed onto a FTIR-ATR crystal and dried by purging
      nitrogen gas. Spectra were recorded in the mid-infrared region between 4500-850
      cm-1 wavenumbers. Each peak in the spectra was assigned to as organic
      biomolecules according to their chemical bond information. A quantitative
      analysis was performed using peak areas and we also used a hierarchical cluster
      analysis as a multivariate spectral analysis. RESULTS: We obtained FTIR spectra
      of fibroblast samples and assigned the biomolecule origins of the peaks. We
      observed individual heterogeneity in FTIR spectra of GD fibroblast samples,
      confirming the well-known phenotypic heterogeneity in GD at the molecular level.
      Significant alterations in protein, lipid and carbohydrate levels related to the
      enzyme replacement therapy were also observed, which is also supported by cluster
      analysis. CONCLUSIONS: Our results showed that the application of FTIR
      spectroscopy to GD research deserves more attention and detailed studies with an
      increased sample size in order to evaluate its potential in the diagnosis and
      follow-up of GD patients.

PMID- 29211352
TI  - Histopathological evaluation of the effect of locally administered strontium on
      healing time in mandibular fractures: An experimental study.
AB  - BACKGROUND: Mandibular fractures are the most common facial fractures. They can
      be treated by conservative techniques or by surgery. The authors hypothesized
      that the application of a single local dose of strontium chloride would
      accelerate the healing of subcondylar mandibular fractures, shorten the recovery
      time and prevent complications. OBJECTIVES: The aim of the present pilot study
      was to evaluate the effects of a single local dose of strontium chloride on the
      healing of subcondylar mandibular fractures in rats. MATERIAL AND METHODS: This
      randomized experimental study was carried out on 24 male Wistar albino rats. The
      rats were randomly divided into 3 groups: experimental group 1, receiving 3%
      strontium chloride; experimental group 2, receiving 5% strontium chloride; and
      the control group. A full thickness surgical osteotomy was created in the
      subcondylar area. A single dose of strontium solution (0.3 cc/site) was
      administered locally by injection on the bone surfaces of the fracture line
      created. Nothing was administered to the control group. The mandibles were
      dissected on postoperative day 21. The fractured hemimandibles were submitted to
      histopathological examination. RESULTS: The median bone fracture healing score
      was 9 (range: 7-9) in experimental group 1; 8 (range: 7-10) in experimental group
      2; and 7.50 (range: 7-8) in the control group. When the groups were compared in
      terms of bone healing scores, there was a statistically significant difference
      between experimental group 1 and the control group (p < 0.05). CONCLUSIONS: This
      study is the first to show that local strontium may have positive effects on the
      healing of subcondylar mandibular fractures. In the authors' opinion, 3%
      strontium was beneficial for accelerating facial skeleton consolidation and bone
      regeneration in rat subcondylar mandibular fractures. This treatment procedure
      may be combined with closed fracture treatment or a conservative approach.

PMID- 29211353
TI  - Evaluation of NMP22 in bladder cancer patients sensitive to environmental toxins.
AB  - BACKGROUND: Bladder cancer (BC) is recognized as environmentally related. The
      interaction of environmental exposure to chemicals and genetic susceptibility
      seem to play important roles in BC development. In order to improve diagnosis and
      the recognition of BC risk, a group of markers which combine genetic
      susceptibility with detoxification and nuclear matrix protein (NMP22) is
      proposed. OBJECTIVES: The aim of the study was to examine the utility of nuclear
      matrix protein (NMP22) as a diagnostic marker in BC in genetic susceptibility
      (NAT2 slow acetylators) combined with detoxification abilities (glutathione S
      transferase GST and isoenzyme GST-pi). MATERIAL AND METHODS: The NMP22 level in
      urine, N-acetyltransferase 2 (NAT2) genotype and GST activity in hemolysate
      blood, as well as isoenzyme GST-pi level, were determined in the urine and serum
      of 43 patients with BC and from 25 non-cancer controls. NMP22 and isoenzyme GST
      pi levels were measured by ELISA. The NAT2 genotype was examined in DNA isolated
      from whole blood using the PCR (Polymerase Chain Reaction) technique, while the
      activity of GST was determined with the spectrophotometric method. RESULTS: In
      the BC group, NMP22 (p = 0.005) concentration, GST-pi (p = 0.003) in urine and
      GST (p = 0.009) activity in blood were statistically significantly higher than in
      the healthy controls. The majority of BC patients were slow acetylators (NAT2
      genotype). A correlation between the level of nuclear matrix protein NMP22 and
      GST was found in all BC group (p = 0.007) and also slow acetylators (p = 0.0147).
      CONCLUSIONS: The results support the utility of a marker combination, which
      covers the genetic susceptibility to chemicals with the level of detoxification
      and nuclear matrix protein in BC patients. A relationship between NMP22 level in
      urine, GST level in blood and NAT2 genotype was observed. Also the isoenzyme GST
      pi in urine seems useful as a marker of BC.

PMID- 29211354
TI  - Correlations between iron content in knee joint tissues and chosen indices of
      peripheral blood morphology.
AB  - BACKGROUND: Iron as a cofactor of enzymes takes part in the synthesis of the bone
      matrix. Severe deficiency of iron reduces the strength and mineral density of
      bones, whereas its excess may increase oxidative stress. In this context, it is
      essential to determine the iron content in knee joint tissues. OBJECTIVES: The
      study objective was to determine the level of iron in the tissues of the knee
      joint, i.e., in the femoral bone, tibia and meniscus. MATERIAL AND METHODS:
      Material for analysis was obtained during endoprosthetic surgery of the knee
      joint. Within the knee joint, the tibia, femur and meniscus were analyzed.
      Samples were collected from 50 patients, including 36 women and 14 men. The
      determination of iron content was performed with the ICP-AES method, using Varian
      710-ES. RESULTS: The lowest iron content was in the tibia (27.04 MUg/g), then in
      the meniscus (38.68 MUg/g) and the highest in the femur (41.93 MUg/g).
      Statistically significant differences were noted in the content of iron in knee
      joint tissues. CONCLUSIONS: In patients who underwent endoprosthesoplasty of the
      knee joint, statistically significant differences were found in the levels of
      iron in various components of the knee joint. The highest iron content was found
      in the femoral bone of the knee joint and then in the meniscus, the lowest in the
      tibia. The differences in iron content in the knee joint between women and men
      were not statistically significant.

PMID- 29211355
TI  - Tumor marker alpha-fetoprotein receptor does not discriminate between benign
      prostatic disease and prostate cancer.
AB  - BACKGROUND: The alpha-fetoprotein receptor (RECAF) is a proposed novel tumor
      marker for detecting several different types of tumors, including prostate cancer
      (PCa). OBJECTIVES: The aim of the study was to evaluate RECAF in discriminating
      benign prostatic conditions from PCa and to compare it with prostate-specific
      antigen (PSA). MATERIAL AND METHODS: A total of 64 patients with elevated serum
      PSA levels and/or abnormal digital rectal examination of the prostate referred to
      a tertiary center for transrectal ultrasound (TRUS) biopsy of the prostate were
      prospectively enrolled in the study from January 2009 to April 2010. Serum RECAF,
      total PSA (tPSA) and free PSA (fPSA) concentrations were measured. The results
      were correlated with histopathologic findings using the Mann-Whitney U test and
      Kruskal-Wallis chi2 test. RESULTS: The median RECAF concentration was 5.34 U/L in
      the benign pathology group of patients and 4.72 U/L in the malignant pathology
      group. The difference was not statistically significant. RECAF density, tPSA and
      fPSA concentrations and tPSA density were significantly different between the
      benign and malignant pathology groups (p = 0.033, p = 0.000, p = 0.002 and p =
      0.000, respectively). RECAF concentration and RECAF density did not differ
      significantly in the subgroups of PCa patients stratified according to Gleason
      score, predominant primary Gleason grade or maximum primary Gleason grade, but in
      predominant secondary Gleason grade and maximum secondary Gleason grade,
      significant differences were found (p = 0.007 and p = 0.004, respectively).
      CONCLUSIONS: The results of the study did not confirm the RECAF tumor marker as
      an alternative way to discriminate between groups of patients with benign
      prostatic conditions and PCa, and its concentration and density do not differ
      among PCa histopathologic groups.

PMID- 29211356
TI  - Usefulness of carcinoembryonic antigen in the diagnosis of small cell lung cancer
      combined with adenocarcinoma.
AB  - BACKGROUND: Small cell lung cancer (SCLC) includes pure SCLC and SCLC combined
      with other pathologies (C-SCLC). C-SCLC accounts for about 28% of all SCLCs
      subjected to surgical resection, but only about 1%-3% of C-SCLCs are detected by
      biopsy. Since less than 5% of SCLC patients are eligible for surgery, it is
      necessary to develop alternative methods for the detection of C-SCLC. OBJECTIVES:
      We determined whether serum carcinoembryonic antigen (CEA) levels, which are
      usually elevated in lung adenocarcinomas, could be used to differentiate between
      pure SCLC and SCLC combined with adenocarcinoma. MATERIAL AND METHODS: We
      reviewed the records of 41 SCLC patients (35 with pure SCLC, 6 with C-SCLC) who
      underwent surgical resection between 2000 and 2014 in Zhejiang Cancer Hospital.
      Their preoperative serum CEA levels were noted, and the relationship between CEA
      level and the type of SCLC was analyzed. RESULTS: Serum CEA levels >6ng/mL were
      found more frequently in C-SCLC patients than in pure SCLC patients (p = 0.031).
      No such difference was observed when a CEA cut-off of 5ng/mL was used (p =
      0.316). CONCLUSIONS: A preoperative serum CEA of >6ng/mL may be used as a
      reference in the diagnosis of SCLC combined with adenocarcinoma.

PMID- 29211357
TI  - Oxidative stress parameters in patients with prostate cancer, benign prostatic
      hyperplasia and asymptomatic inflammatory prostatitis: A prospective controlled
      study.
AB  - BACKGROUND: The imbalance between oxidant and reductant mechanisms creates a
      nidus for the etiopathogenesis of several diseases. In this study, we aimed to
      compare the oxidative stress (OS) parameters in patients who were diagnosed with
      prostate cancer (pCa), benign prostatic hyperplasia (BPH) or asymptomatic
      inflammatory prostatitis (AIP), according to the histopathologic examination of
      transrectal ultrasonographic prostate biopsy and transurethral prostate resection
      specimens. OBJECTIVES: In this study, we aimed to compare oxidative stress
      between histologically proven prostate cancer, hyperplasia and prostatitis.
      MATERIAL AND METHODS: According to histopathologic examinations, 97 patients were
      divided into 3 study groups: group 1: pCa (n = 30), group 2: BPH (n = 41), and
      group 3: AIP (n = 26). Finally, 30 patients were enrolled in a control group. MDA
      levels, CuZn-SOD, Se-GPx, CAT activities, and trace element levels were
      evaluated. RESULTS: A statistically significant difference between prostate
      cancer and other groups were documented in terms of MDA activity. Contrary to
      AIP, a statistically significant difference has also been encountered between BPH
      and the control group. Decreased CuZn-SOD enzyme levels were found in PCa and BPH
      patients without statistical significance. Increased CAT activity was also
      documented in PCa, BPH and AIP patients. No significant difference in GPX
      activity was documented between the groups, except BPH and control group. Trace
      element levels were low in the patients with prostate cancer and BPH when
      compared with the control group. CONCLUSIONS: Despite the data regarding OS in
      PCa patients, there is a paucity of data regarding BPH and especially AIP
      patients. Our study revealed obvious oxidative stress in BPH and PCa patients as
      opposed to AIP. Assessing the oxidative stress in these patients may assist in
      the future prevention, diagnosis and also treatment. However, the question
      whether the presence of OS-related parameters and drugs could be used for the
      diagnosis or management of prostatic diseases, needs to be addressed in future
      larger and better studies with a more rational basis.

PMID- 29211358
TI  - Chest HRCT findings in patients with primary Sjogren's syndrome.
AB  - BACKGROUND: Pulmonary manifestations (PMs) in primary Sjogren's syndrome (pSS)
      are among the most frequent extraglandular complications, with reported
      prevalence varying widely (9-75%), depending on the methods of detection.
      OBJECTIVES: The aim of this study was to assess the incidence of PMs in pSS and
      to determine the factors predisposing to the occurrence of this complication.
      MATERIAL AND METHODS: The study group consisted of 68 patients with pSS. Among
      the patients who were possibly affected by PMs, chest High Resolution Computed
      Tomography (HRCT) was performed. RESULTS: In the group of all patients afflicted
      with pSS, 30 people indicated the need to expand medical imaging via chest HRCT
      scan. (The most frequent reason, in 80%, was persistent, dry cough periodically
      waking up patients at night). The chest HRCT scan revealed lung tissue changes in
      the course of 29% of all examined patients (of 68). No correlation was found
      between the occurrence of HRCT changes and the age of patients (p = 0.8),
      increased CRP > 5 mg/1 (p = 0.1) or ESR > 20 mm/h (p = 0.9), focus score (p =
      0.8), leucopenia (p = 0.5), RF value (p = 0.3), gamma globulin value (p = 0.5),
      intensity of eye and oral cavity dryness (p = 0.6; 0.3) and smoking cigarettes.
      Additionally, no correlation was found between more frequent occurrences of
      antibodies anti-SSA, anti-SSB or anti-Ro52 and HRCT changes (p = 0.3; 0.07; 0.4).
      Pertaining to the clinical signs, HRCT changes occurred more often only in
      patients suffering from peripheral arthritis (p < 0.01). CONCLUSIONS: PM is a
      frequent symptom of pSS. A factor predisposing to the development of changes in
      the respiratory system was not found. Changes in HRCT occur more frequently in
      patients with peripheral arthritis.

PMID- 29211359
TI  - Continent catheterizable conduits in pediatric urology: One-center experience.
AB  - BACKGROUND: Clean intermittent catheterization (CIC) is a standard treatment for
      patients who are unable to empty the bladder. In the absence of the urethra or if
      catheterization through the urethra is problematic, a continent vesicostomy is
      used as a catheterizable conduit. The Malone procedure is an established
      treatment option for children with neurogenic constipation and fecal
      incontinence. OBJECTIVES: The aim of the study was to report the authors'
      experience with continent catheterizable conduits (CCCs) in children, to review
      the results and to determine the efficacy of the technique, with an emphasis on
      continence and the need for revision. MATERIAL AND METHODS: The retrospective
      study involved children who underwent catheterizable conduit procedures from 2000
      to 2015. Two kinds of continent stomas were performed: Mitrofanoff vesicostomies
      for CIC and Malone antegrade continence enemas (MACEs). The 115 patients treated
      included 66 girls and 49 boys. A total of 134 operations were performed; 62 were
      Mitrofanoff vesicostomies and 72 were Malone appendicostomies. In 19 cases, both
      Mitrofanoff and Malone appendicostomies were formed out of 1 appendix divided
      into 2 parts. In 5 children vesicocutaneous stomas were constructed using Monti's
      procedure, and in 1 it was constructed from an intussuscepted ileal loop. In 27
      patients Malone procedures were performed laparoscopically. RESULTS: The mean
      follow-up period was 8.6 years. There was no serious morbidity in relation to the
      surgery. In 9 children local wound infection was noted, and in 9 others stomal
      stenosis developed. Out of the 62 children with catheterizable vesicostomies, 59
      were continent. The MACE procedure was successful in all 72 patients; problems
      with constipation and fecal incontinence were resolved in all cases. None of the
      laparoscopies needed conversion. CONCLUSIONS: Continent catheterizable conduits
      help patients achieve both fecal and urinary continence. Laparoscopy is effective
      in performing the Malone procedure. Stoma-related complications could be avoided
      using end-to-side appendix anastomoses to the skin. Stomal incontinence is rare
      even when a simplified technique is employed, using the appendix without
      cecoplication.

PMID- 29211360
TI  - Cerebral venous thrombosis as a diagnostic challenge: Clinical and radiological
      correlation based on the retrospective analysis of own cases.
AB  - BACKGROUND: Cerebral venous thrombosis (CVT) is a rare condition which
      constitutes 0.5-1% of all strokes. The clinical and radiological picture of CVT
      is non-specific and can mimic other disorders. OBJECTIVES: The aim of the study
      was to retrospectively evaluate and correlate clinical and radiological symptoms
      presented by patients with CVT, both in the initial and follow-up neurological
      and neuroimaging examinations, with a special emphasis on diagnostic
      difficulties. MATERIAL AND METHODS: Material consisted of 11 patients with CVT (7
      women, 4 men). The average age was 43.5, ranging from 23 to 69 years. Clinical
      symptoms, laboratory findings, risk factors and the results of neuroimaging
      examinations including CT, MRI and DSA were retrospectively analyzed and
      correlated. RESULTS: All subjects developed superficial CVT and 1 also deep CVT,
      with no parenchymal lesions in 2 cases, non-hemorrhagic infarctions in 3 and
      hemorrhagic lesions in 6 subjects. The most frequent symptoms were headache,
      seizures and hemiparesis. The major risk factors were hormonal therapies in women
      and congenital thrombophilia. Factors influencing the clinical course and outcome
      the most were location and type of brain lesions, with hemorrhagic cortical
      infarctions bringing the worst prognosis and being associated with the highest
      rate of persistent neurological deficits, despite the rate of vessel
      recanalization. CONCLUSIONS: In our opinion, quick diagnosis before parenchymal
      hemorrhagic lesions are visible on CT is of crucial importance and requires a
      constant alertness and good cooperation of neurologists and radiologists,
      especially in emergency settings.

PMID- 29211361
TI  - Accumulation of mutations in reverse transcriptase of hepatitis B virus is
      associated with liver disease severity in treatment-naive Chinese patients with
      chronic hepatitis B.
AB  - BACKGROUND: Mutations in reverse transcriptase (RT) of the hepatitis B virus
      (HBV) are demonstrated to be strongly associated with nucleos(t)ide analog
      resistance, which is supposed to be the biggest obstacle during the long-term
      anti-viral treatment of chronic hepatitis B. However, the presence of RT
      mutations in treatment-naive chronic hepatitis B patients and its clinical
      significance are not well known. OBJECTIVES: To investigate the significance of
      mutations in reverse transcriptase of the hepatitis B virus in treatment-naive
      Chinese patients with chronic hepatitis B. MATERIAL AND METHODS: In this study,
      288 treatment-naive chronic HBV patients were recruited and the RT region was
      sequenced. The results showed that 71 patients (24.65%) were found with RT
      mutations, within which there were no well-defined primary nucleotide analog
      resistant mutations. RESULTS: There were a total of 28 mutant sites, which formed
      three dominant mutant clusters: rt124-139, rt191-212 and rt225-229. Among these
      71 patients, 63.38% (45/71) of patients had a single mutation while 19.72%
      (14/71), 12.68% (9/71) and 4.23% (3/71) of patients had 2, 3 or 4 mutations,
      respectively. Patients with RT mutations showed significantly decreased serum
      baseline HBV DNA loads (p = 0.0363) and blood platelet count (p = 0.0181) than
      patients without RT mutations. Patients with multiple mutant sites (>= 2) had
      significantly decreased baseline HBV DNA loads (p = 0.0004) and blood platelet
      count (p = 0.0011) than patients with single mutant site. Moreover, the number of
      RT mutant sites is significantly associated with severity of liver fibrosis (p =
      0.0128). CONCLUSIONS: This study demonstrated that there was a prevalence of RT
      mutations in treatment-naive chronic hepatitis B patients, which reflects a
      tougher liver environment for the virus and deeper liver injury for the host.
      Accumulation of RT mutations was associated with liver disease severity in
      treatment-naive chronic hepatitis B patients.

PMID- 29211362
TI  - Clinical differences of Helicobacter pylori infection in children.
AB  - Helicobacter pylori infection is widely spread all over the world. The prevalence
      of H. pylori infection in the world varies and depends on numerous factors such
      as age, ethnicity, geographical and socioeconomic status. Humans have been in a
      symbiotic relationship with this bacterium for thousands of years. However 10-20%
      of people infected with H. pylori are likely to develop gastroduodenal diseases
      such as peptic ulcer disease, iron deficiency anemia, gastric mucosal atrophy,
      metaplasia, dysplasia, MALT lymphoma, or gastric adenocarcinoma. Most of these
      diseases develop as the infection progresses and they are likely to occur later
      in life among the elderly. In the following years, the use of modern molecular
      techniques has led to the discovery of new Helicobacter strains and their
      genotypic differentiation. Newly discovered Helicobacter microorganisms can
      colonize human gastrointestinal tract and bile ducts. This article summarizes the
      distinct features of H. pylori infection in children including its prevalence,
      clinical manifestation, indications for treatment and recommended schemes of
      eradication.

PMID- 29211363
TI  - Hierarchical potential differentiation of liver cancer stem cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant tumors in Chinese
      people and offers poor prognosis. Tumor tissue, like normal tissue, is
      hierarchically differentiated. Thus, minor tumor cell populations able to
      differentiate, such as stem cells, sustain tumor self-renewal and proliferation.
      The fact that liver cancer stem cells (CSCs) with different surface markers
      appear heterogeneous with respect to oncogenesis and drug resistance indicates
      that subpopulations of surface markers preserve the hierarchical potential of
      differentiation during proliferation, deterioration and relapse. The epithelial
      to mesenchymal transition (EMT) is correlated to tumor malignancy and aggression,
      and hepatocytes bearing EMT have obvious hierarchical differentiation potential
      with respect to signaling pathways such as transforming growth factor beta,
      Wnt/beta-catenin and microRNA. Therefore, it may be more effective for early
      diagnosis to monitor HCC recurrence using peripherally circulating CSCs, and
      these may also offer potential for HCC immunotherapy or for targeting HCC
      treatment using these markers. Thus, we reviewed the generation, hierarchical
      differentiation and clinical application of hepatic CSCs.

PMID- 29211364
TI  - Insights into novel anticancer applications for apigenin.
AB  - Flavonoids, naturally occuring derivatives of 2-phenyl-benzo-gamma-pyrone, are
      widespread in plants as coloring substances. Apigenin (4',5,7,-trihydroxyflavone
      (5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), molecular formula
      C15H10O5, is a flavonoid present in many fruits and vegetables, primarily in
      citrus fruits, apples, parsley and celery leaves. It is also found in some
      medicinal plants, including chamomile flowers, thyme, oregano, peppermint, lemon
      balm and yarrow, as a 7-O-glycoside with anti-inflammatory and antioxidant
      activity. In recent years it has attracted a great deal of interest as a
      bioactive substance reported to have anticancer properties. According to recent
      literature data, apigenin is able to reduce cancer cell glucose uptake, inhibit
      remodeling of the extracellular matrix, inhibit cell adhesion molecules that
      participate in cancer progression and hinder the development of blood vessels
      needed by growing tumors. It is reported to protect against a wide variety of
      cancers. The mechanism of anticancer activity is still under investigation and
      further research is needed.

PMID- 29211365
TI  - Oral cavity health among cystic fibrosis patients: Literature overview.
AB  - Cystic fibrosis is a genetic disorder in which the mutation of the Cystis
      Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes the protein
      forming a chloride channel of epithelial cells results in its distorted
      functioning. The manifestations of the disorder are mainly observed in the
      respiratory and digestive system. Accumulation of sticky and thick mucus is the
      dominant clinical symptom; it leads to chronic infections and gradual tissue
      destruction. Although cystic fibrosis remains incurable, it is currently feasible
      to extend patients' life expectancy thanks to modern therapy possibilities. As
      cystic fibrosis is no longer the domain of pediatricians, health care to CF
      patients needs to be provided by doctors of various specializations. The
      multidisciplinary team of doctors should include a dentist aware of specific
      prevention and treatment needs of this group of patients. It results from the
      fact that in the course of cystic fibrosis it is possible to observe a variety of
      changes in the oral cavity environment. The study presents dental issues observed
      in CF patients and reported in literature. Particular attention was paid to
      dental caries, mineralization disorders of hard dental tissues, gingivitis and
      the change in the content and properties of saliva; moreover, prevention and
      treatment options regarding oral cavity health is this group of patients were
      taken into consideration.

PMID- 29211366
TI  - Trace metal ions release from fixed orthodontic appliances and DNA damage in oral
      mucosa cells by in vivo studies: A literature review.
AB  - An overview of professional literature referring to the release of metal ions
      from fixed orthodontic appliances and their influence on oral mucosa in
      conditions of in vivo are presented, along with a detailed analysis of the
      exposure of the cells of cheek mucosa epithelium to metal ions. Electronic
      databases (PubMed, Elsevier, Ebsco) were searched with no language restrictions.
      The relevant orthodontic journals and reference lists were checked for all
      eligible studies. A total of 38 scientific articles were retrieved in the initial
      search. However, only 7 articles met the inclusion criteria. Statistically
      significant differences in the levels of the amount of nickel ions, cobalt ions
      and chromium ions were observed in cells of cheek mucosa. The most biocompatible
      material used in the production of fixed orthodontic appliances is titanium, and
      the least biocompatible material is steel, which releases the largest amount of
      nickel and chromium. Metal ions are released from fixed orthodontic appliances
      only in the first phase of treatment. It is recommended to conduct further, long
      term research on a larger number of patients to define the influence of using
      fixed orthodontic appliances and biological effect they might have on tissues.

PMID- 29211367
TI  - Coronary artery disease: New Insights into revascularization treatment of
      diabetic patients.
AB  - Diabetes mellitus is an independent cardiovascular risk factor, considered an
      equivalent of coronary artery disease in terms of prognosis. A history of acute
      coronary syndrome is a strong predictor of another coronary episode, and
      cardiovascular complications are the leading cause of mortality in diabetic
      patients. Many patients with coronary artery disease suffer from concomitant
      diabetes or pre-diabetes. There are 3 strategies of coronary artery disease
      treatment: conservative management, coronary artery bypass graft (CABG) and
      percutaneous coronary intervention (PCI). Since drug-eluting stents (DES) were
      developed, PCI has become one of the most widespread interventional cardiology
      procedures performed in Europe and worldwide. Among all coronary risk factors,
      diabetes mellitus remains the most important predictor of unfavorable outcomes of
      revascularization therapy. This paper reviews the current evidence regarding
      revascularization in diabetic patients, with particular emphasis on PCI. A
      systematic analysis of clinical trials of CABG and PCI, especially with DES, was
      conducted.

PMID- 29211368
TI  - ?

PMID- 29211369
TI  - [Rare vascular diseases, building dedicated multidisciplinary specialized
      center].
AB  - Rare Vascular Diseases (RVD) encompass different types of vessel involvement.
      Some cause a dilation, others a weakening or tortuosity of the arterial wall,
      others an obstruction or excessive calcification of arterial walls. Clinical
      pathway of patients with RVD to diagnosis is often long and complex. Thus, in
      order to allow early diagnosis and coordinated multidisciplinary management and
      follow-up, a specialized RVD centre has been set-up at the CHUV, following the
      framework of the national concept of rare diseases.

PMID- 29211370
TI  - [The treatment of venous malformations in adult patients: the role of US-guided
      sclerotherapy].
AB  - Venous malformations are slow flow dysplastic lesions, constituted by a vascular
      nest without arterial or capillary connections, more or less independent of the
      normal venous anatomy and circulation. In certain cases a treatment is required
      for symptom relief or for natural complications management. The percutaneous
      sclerotherapy under ultrasound guidance is increasingly used as an effective and
      mini-invasive option, allowing obtaining very good results with minor side
      effects. Several substances have been used with different efficacy and side
      effects rate. We review the literature and present some cases.

PMID- 29211371
TI  - [Primary lymphedema].
AB  - Characterized by an aplasia, hypoplasia or dysplasia of the lymphatic network,
      the primary lymphedema takes part of rare diseases. If 10 % of cases are
      congenital, the majority of them are detected before 35 years, most of the time
      due to an intercurrent event suh as a sprain or an infection. Although rarer,
      some primaries lymphedemas are family forms such the syndromes of Milroy and
      Meige. The primary lymphedema can also be a part of more complex malformative
      diseases such as Klinefelter, Turner or Noonan syndromes. If the lymphatic
      drainage associated with the elastic contention remains the basis care of
      lymphedema, we have to identify these patients as well as their family, sometimes
      requiring multidisciplinary cares.

PMID- 29211372
TI  - [Thromboangiitis obliterans: notions for practice].
AB  - Thromboangiitis obliterans is an occlusive vasculopathy affecting small- and
      medium-size arteries. It can result in severe ischemic status. Thrombophlebitis
      can be associated. The exact etiology has still to be elucidated. Smoking is the
      main contributing factor. Diagnosis is based on clinic and paraclinic context, as
      well as exclusion of other vascular pathologies. Its management consists in
      complete smoking cessation and instauration of vasodilator treatment.
      Revascularization is an option that has to be evaluated on a case by case basis.
      New promising therapeutic approaches are emerging.

PMID- 29211373
TI  - [Deep vein thrombosis in uncommon localisations].
AB  - Venous thromboembolism (VTE) with its two components, deep vein thrombosis (DVT)
      and pulmonary embolism (PE), is a common disease with an incidence of 0,75
      2,69/1000. Deep vein thrombosis is localized in unusual sites in about 10 %, and
      rare DVT's have specific symptoms and risk factors. Uncommon DVT's are often
      related to local factors, inflammation, cancer, hematologic diseases and
      thrombophilia. Their diagnostic workup is less straightforward than in suspected
      VTE of lower limbs and PE, and rare DVT's are often unexpected findings of
      imaging studies. By extrapolating evidence of lower limbs VTE, most rare DVT are
      treated by anticoagulants, except retinal vein thrombosis. However, evidence for
      the type and duration of anticoagulation is limited.

PMID- 29211374
TI  - [Splanchnic vein thrombosis].
AB  - Splanchnic vein thromboses include thrombosis of the portal venous system
      (including the portal, mesenteric and splenic vein) and hepatic vein thrombosis
      (also called Budd-Chiari syndrome). They are rare manifestations of venous
      thromboembolism. These thromboses are frequently associated with local or
      systemic factors. The therapeutic approach is often complex due to heterogeneity
      of patients and limited available data in the literature. The cornerstone of
      treatment is anticoagulation. However, the bleeding risk, related to portal
      hypertension, should be accurately assessed to individualize the treatment. A
      multidisciplinary consultation team including several specialists is provided at
      the University Hospitals of Geneva for the optimal management of those patients.

PMID- 29211375
TI  - ?

PMID- 29211376
TI  - ?

PMID- 29211377
TI  - ?

PMID- 29211378
TI  - ?

PMID- 29211379
TI  - ?

PMID- 29211380
TI  - ?

PMID- 29211381
TI  - Cleft lip and palates and breastfeeding.

PMID- 29211382
TI  - Rebel Heart: How an elite team of Air Force Pararescuemen saved a sick baby a
      thousand miles out at sea.

PMID- 29211383
TI  - Perspectives of key stakeholders and experts in infant feeding on the
      implementation of the Australian National Breastfeeding Strategy 2010-2015.
AB  - Breastfeeding is widely accepted as an important public health issue for babies
      and their mothers. Yet, despite this, Australia continues to struggle with
      reaching global targets for breastfeeding indicators. In 2007, the Best Start
      Parliamentary Inquiry Report was released and set the stage for the Australian
      National Breastfeeding Strategy [2010-2015), which was announced in November
      2009, with the vision to increase Australia's breastfeeding rates of infants at 6
      months of age and beyond. The aim of this research project was to explore the
      perspectives of key stakeholders in the field of infant feeding in Australia on
      the implementation of the strategy, barriers and enablers to its successful
      implementation and actions that were still needed. Using qualitative research
      methods of in-depth, semi-structured interviews and thematic analysis, this study
      identifies main themes of these perceptions about the strategy implementation and
      some recommendations for future strategies and further research. The main themes
      identified were initial opinions of the strategy as a blueprint for action, the
      strategy as a driver for action, lessons learned and recommendations for the
      future. For success in improving implementation of national breastfeeding
      strategies, it is recommended that Australia establish an independent
      breastfeeding/infant feeding committee, increase the political prioritisation of
      issues surrounding infant feeding and strengthen the regulation of the marketing
      of breastmilk substitutes.

PMID- 29211384
TI  - New Zealand women talk about breastfeeding support from male family members.
AB  - AIM: Little research has been done to investigate the influence of male family
      members' support for breastfeeding. This article considers the influence of male
      partners and other male family members on the initiation and duration of
      exclusive breastfeeding. METHODS: Thirty heterosexual New Zealand women who had
      identified in a short antenatal questionnaire that they intended to breastfeed
      exclusively for 6 months were recruited. The qualitative research included a face
      to-face postpartum interview followed by monthly audio-recorded telephone
      interviews that stopped at 6 months. The participants' narratives were analysed
      using thematic analysis. KEY FINDINGS: Five key themes related to breastfeeding
      support from male family members were identified: a) male partners did not have
      enough knowledge about breastfeeding, b) male partners wanted to share infant
      feeding, c) participants received emotional and practical support from their male
      partners, d) male partners supported breastfeeding in public, e) some women
      received crucial breastfeeding support from male family members who were not the
      father of the baby. CONCLUSION: Comments from participants suggest that some New
      Zealand men are actively involved in supporting breastfeeding in their nuclear
      and extended families. Several participants suggested that male support was as
      effective as support from female family members.

PMID- 29211385
TI  - Bringing babies and breasts into workplaces: Support for breastfeeding mothers in
      workplaces and childcare services at the Australian National University.
AB  - In 1999, two leading Australian academics challenged Australian universities to
      lead moves to better manage employees' maternity and breastfeeding needs, and
      'bring babies and breasts into workplaces'. This paper addresses the question of
      how universities cope with the need for women to breastfeed, by exploring
      barriers facing women who combine breastfeeding and paid work at the Australian
      National University (ANU). Data were collected through online surveys in 2013
      using mixed method, case study design, nested within a larger national study.
      Participants were 64 working mothers of children aged 0-2 years from the ANU
      community of employees and users of on-campus child care. Responses highlighted
      the ad hoc nature of support for breastfeeding at ANU. Lack of organisational
      support for breastfeeding resulted in adverse consequences for some ANU staff.
      These included high work-related stresses and premature cessation of
      breastfeeding among women who had intended to breastfeed their infants in line
      with health recommendations.

PMID- 29211387
TI  - Iconic Moments in EMS: Recognizing the moments, people, technologies and ideas
      that shaped modern EMS.

PMID- 29211386
TI  - Blood Therapy: Considerations for using blood products for prehospital trauma
      patients.

PMID- 29211388
TI  - Scene Safety Signs: Evaluating industrial hazmat team maturity provides vital
      scene safety information.

PMID- 29211389
TI  - Still LEAPing to wrong conclusions?

PMID- 29211390
TI  - Engaging mothers: Breastfeeding experiences recounted (EMBER). A pilot study.
AB  - BACKGROUND: There is an abundance of published literature that describes the
      short- and long-term effects of breastfeeding for both the infant and mother.
      Despite the majority of women having good intentions to breastfeed, challenges
      that they encounter place their breastfeeding journey in jeopardy. Improving
      breastfeeding rates and durations is a significant public health priority at a
      local, national and international level. AIM: This pilot study aimed to identify
      and describe participating women's breastfeeding experiences in order to better
      understand why some achieve their breastfeeding goals, despite experiencing
      challenge and others do not. METHOD: A qualitative methodology was chosen to
      allow these mothers to have their voices heard. Twenty Australian Breastfeeding
      Association trainee counsellors, who were undertaking the Certificate IV in
      Breastfeeding Education, gave permission for the examination and analysis of
      their de-identified reflections on their own breastfeeding experiences. Data was
      examined and thematically analysed into identified themes. RESULTS: Participants'
      breastfeeding experiences were identified into six themes: 1. expectation of
      breastfeeding, 2. motivation to breastfeed, 3. support to maintain breastfeeding,
      4. returning to work, 5. the experience of breastfeeding and 6. social attitude
      to public breastfeeding. The responses and experiences were varied, with each
      woman describing a particular event that had a significant impact on her
      breastfeeding journey. CONCLUSION: It is not completely understood why some
      mothers continue with their breastfeeding journey, whilst others discontinue
      earlier than they had planned. Women in this pilot study reported that support,
      acceptability of breastfeeding to their family and social circle, public
      breastfeeding, issues around infant sleep and maternal fatigue were all
      significant issues for them as they navigated breastfeeding for the first time. :
      Findings from this pilot study will be used to inform the development of a larger
      study which will further explore women's decision making, as well as identify
      what supports are needed to improve women's experience of breastfeeding.

PMID- 29211391
TI  - Feelings of failure: Early weaning.
AB  - ... it was horrible - a difficult, painful and agonizing process. ... Nothing I
      tried made it anything but torture. Finally, my son got a mouthful of blood, and
      I gave up. I felt like a failure. It added to my depression, made me question my
      ability to mother, and caused my infant to lose too much weight. (The American
      Dietetic Association's) position paper has no loopholes for us 'failures', no
      compassion for those of us too poor to rent an electric pump ... Could you please
      let us off the hook? (Saban, 2002, p. 24)  I can't say what a devastating
      experience failing to breastfeed Bianca was for me. I was left feeling like I'd
      failed her as a mother, and even as a woman. I found it difficult to talk about,
      and was loath to bottle feed Bianca in public.

PMID- 29211392
TI  - Low level laser therapy for breastfeeding problems.
AB  - Breast and nipple pain, nipple damage and mastitis are common reasons given by
      women for their early cessation of breastfeeding. There are a limited number of
      effective therapies available to support healing of damaged nipples during
      lactation. Low level laser therapy is a painless treatment, which appears to
      accelerate wound healing and ease pain. We present two case studies, which
      demonstrate the use of low level laser therapy in clinical practice.

PMID- 29211393
TI  - The impact of metformin use on the risk of prostate cancer after prostate biopsy
      in patients with high grade intraepithelial neoplasia.
AB  - PURPOSE: We report our experience on metformin use in diabetic patients and its
      impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial
      neoplasia (HGPIN) diagnosis. MATERIALS AND METHODS: We retrospectively analyzed
      551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy.
      The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic
      patients. Among the patients with diabetes 44 were treated with metformin, and 51
      with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme
      with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN.
      RESULTS: Among 195 (35.4%) patients with cancer, there were statistically
      significant differences in terms of PCa detection (p<0.001), Gleason score
      distribution (p<0.001), and number of positive biopsy cores (pv0.002) between
      metformin users and non-users. Metformin use was associated with a decreased risk
      of PCa compared with neveruse (p<0.001). Moreover, increasing duration of
      metformin assumption (>=2 years) was associated with decreasing incidence of PCa
      and higher Gleason score >=7 compared with assumption <2 years. CONCLUSIONS: This
      preliminary experience suggests that metformin use may have some beneficial
      effects in patients with diabetes and HGPIN; metformin should not be overlooked
      in these patients because it is neither new nor expensive.

PMID- 29211395
TI  - Left ureteral appendiceal interposition: exercise caution and do not be mislead
      by postoperative radiological obstruction.
AB  - Postoperative imaging after appendiceal ureteral interposition may be difficult
      to interpret, misguiding the urologist towards intervention. We present a case in
      which radiological obstruction was not endorsed by a 99TcDTPA nephrogram, with
      favorable outcome after conservative treatment.

PMID- 29211394
TI  - Ureteroileal bypass: a new technic to treat ureteroenteric strictures in urinary
      diversion.
AB  - OBJECTIVE: To present our technique of ureteroileal bypass to treat uretero
      enteric strictures in urinary diversion. MATERIALS AND METHODS: One hundred and
      forty-one medical records were reviewed from patients submitted to radical
      cystectomy to treat muscle-invasive bladder cancer between 2013 and 2015. Twelve
      (8.5%) patients developed uretero-enteric anastomotic stricture during follow-up.
      Five patients were treated with endoscopic dilatation and double J placement.
      Four were treated surgically with standard terminal-lateral implantation. Three
      patients with uretero-enteric anastomotic stricture were treated at our
      institution by "ureteroileal bypass", one of them was treated with robotic
      surgery. RESULTS: All patients had the diagnosis of uretero-enteric anastomotic
      stricture via computerized tomography and DTPA renal scan. Time between
      cystectomy and diagnosis of uretero-enteric anastomotic stricture varied from
      five months to three years. Mean operative time was 120+/-17.9 minutes (98 to 142
      min) and hospital stay was 3.3+/-0.62 days (3 to 4 days). Mean follow-up was 24+/
      39.5 months (6 to 72 months). During follow-up, all patients were asymptomatic
      and presented improvement in ureterohydronephrosis. Serum creatinine of all
      patients had been stable. CONCLUSIONS: Latero-lateral ureter re-implantation is
      feasible by open or even robotic surgery with positive results, reasonable
      operation time, and without complications.

PMID- 29211396
TI  - Retroperitoneal approach for robot-assisted partial nephrectomy: technique and
      early outcomes.
AB  - OBJECTIVES: The aim of our study is to present early outcomes of our series of
      retroperitoneal-RAPN (Robot Assisted Partial Nephrectomy). MATERIALS AND METHODS:
      From September 2010 until December 2015, we performed 81 RAPN procedures (44 at
      left kidney and 37 at right). Average size was 3cm (1-9). Average PADUA score 7.1
      (5-10). Average surgical time (overall and only robot time), ischemia time, blood
      loss, pathological stage, complications and hospital stay have been recorded.
      RESULTS: All of the cases were completed successfully without any operative
      complication or surgical conversion. Average surgical time was 177 minutes (75
      340). Operative time was 145 minutes (80-300), overall blood loss was 142cc (60
      310cc). In 30 cases the pedicle was late clamped with an average ischemia time of
      4 minutes (2-7). None of the patient had positive surgical margins at definitive
      histology (49pT1a, 12pT1b, 3pT2a, 2pT3a). Hospital stay was 3 days (2-7).
      CONCLUSIONS: The retroperitoneal robotic partial nephrectomy approach is safe and
      allows treatment of even quite complex tumors. It also combines the already well
      known advantages guaranteed by the da Vinci(r) robotic surgical system, with the
      advantages of the retroperitoneoscopic approach.

PMID- 29211397
TI  - Efficacy of targeted therapy for advanced renal cell carcinoma: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - We conducted a systematic review and meta-analysis of the literature on the
      efficacy of the targeted therapies in the treatment of advanced RCC and, via an
      indirect comparison, to provide an optimal treatment among these agents. A
      systematic search of Medline, Scopus, Cochrane Library and Clinical Trials
      unpublished was performed up to Jan 1, 2015 to identify eligible randomized
      trials. Outcomes of interest assessing a targeted agent included progression free
      survival (PFS), overall survival (OS) and objective response rate (ORR). Thirty
      eligible randomized controlled studies, total twentyfourth trails (5110 cases and
      4626 controls) were identified. Compared with placebo and IFN-alpha, single
      vascular epithelial growth factor (receptor) tyrosine kinase inhibitor and
      mammalian target of rapamycin agent (VEGF(r)-TKI & mTOR inhibitor) were
      associated with improved PFS, improved OS and higher ORR, respectively. Comparing
      sorafenib combination vs sorafenib, there was no significant difference with
      regard to PFS and OS, but with a higher ORR. Comparing single or combination
      VEGF(r)-TKI & mTOR inhibitor vs BEV + IFN-alpha, there was no significant
      difference with regard to PFS, OS, or ORR. Our network ITC meta-analysis also
      indicated a superior PFS of axitinib and everolimus compared to sorafenib. Our
      data suggest that targeted therapy with VEGF(r)-TKI & mTOR inhibitor is
      associated with superior efficacy for treating advanced RCC with improved PFS, OS
      and higher ORR compared to placebo and IFN-alpha. In summary, here we give a
      comprehensive overview of current targeted therapies of advanced RCC that may
      provide evidence for the adequate targeted therapy selecting.

PMID- 29211398
TI  - The effect of AST/ALT (De Ritis) ratio on survival and its relation to tumor
      histopathological variables in patients with localized renal cell carcinoma.
AB  - PURPOSE: To assess the relationship between De Ritis (aspartate aminotransaminase
      [AST]/Alanine aminotransaminase [ALT]) ratio and pathological variables and
      whether it is an independent prognostic factor. MATERIALS AND METHODS: We
      analyzed 298 consecutive patients who underwent radical or partial nephrectomy
      for non-metastatic renal cell carcinoma (RCC) between 2006 and 2015. The
      association between De Ritis ratio and pathological variables including tumor
      size, presence of renal vein invasion, vena cava invasion, renal capsule
      infiltration, Gerota fascia invasion, renal sinus involvement, renal pelvic
      invasion, angiolymphatic invasion, adrenal gland involvement, lymph node
      involvement, tumor necrosis, and Fuhrman's grade was tested. Multivariable Cox
      analysis was performed to evaluate the impact of this ratio on overall survival
      and cancer-specific survival. RESULTS: An increased preoperative De Ritis ratio
      was significantly associated with renal vein invasion, renal capsule infiltration
      and renal pelvis involvement (p<0.05) in non-metastatic RCC. On multivariate
      analysis we found that tumor size, Fuhrman grade and lymph node involvement were
      independent prognostic factors for cancerspecific survival. AST/ALT ratio had no
      influence on the risk of overall and cancerspecific survival. CONCLUSION: An
      increased preoperative AST/ALT ratio had a significant association with renal
      vein invasion, renal capsule infiltration and renal pelvis involvement in
      patients with non-metastatic RCC. However, it does not appear to be an
      independent prognostic marker in non-metastatic RCC.

PMID- 29211399
TI  - OAB score: a clinical model that predicts the probability of presenting
      overactive detrusor in the urodynamic study.
AB  - PURPOSE: To create a predictive model of involuntary detrusor contraction (IDC)
      to improve the diagnostic accuracy of overactive detrusor (OAD), associating
      overactive bladder (OAB) symptoms with other clinical parameters in the female
      population. MATERIALS AND METHODS: A total of 727 women were studied
      retrospectively. In all of them, urodynamic study was conducted for
      urogynecological causes. Demographics information, personal history, symptoms,
      physical exam, a 3-day frequency/volume chart and urinary culture, were collected
      in all patients and they subsequently underwent uroflowmetry and urodynamic
      studies. A logistic regression model was performed in order to determine
      independent predictors of presence of IDC. Odd ratio (OR) estimation was used to
      assign a score to each one of the significant variables (p<=0.05) in the logistic
      regression model. We performed a ROC curve in order to determine the predictive
      ability of the score in relation to the presence of OAD. RESULTS: presence of OAD
      was evident in 210 women (29%). In the logistic regression analysis, independent
      predictors of OAD were urgency, urgency incontinence, nocturia, absence of SUI
      symptoms, diabetes mellitus, reduction of vaginal trophism and bladder capacity
      below 150 mL. The probability of IDC diagnosis increases as the score raises
      (Score 0: 4% until Score >=10: 88%). Sensitivity was 71% and specificity 72%. The
      area under the curve of OAB score was 0.784 (p>0.001). CONCLUSIONS: OAB score is
      a clinical tool that shows higher diagnostic accuracy than OAB symptoms alone to
      predict overactive detrusor.

PMID- 29211400
TI  - Robot-Assisted Nephropexy.
AB  - INTRODUCTION: Renal ptosis is defined as the renal descent when there is a change
      from supine to orthostatic position, usually with a change of two vertebral
      bodies or more than five cm apart. Although rare, it is one of the causes of
      chronic flank pain or of upper abdomen. The typical patient of renal ptosis is
      young, female, thin, with complaint of pain when in an upright position (1, 2).
      OBJECTIVE: Demonstrate a robot-assisted nephropexy technique in a young woman
      diagnosed with symptomatic renal ptosis on the right kidney, confirmed by imaging
      tests. MATERIALS AND METHODS: A 29-year-old female patient with a history of
      chronic right-sided pain and palpable renal mobility on physical examination. The
      diagnosis of renal ptosis was confirmed by ultrasound imaging, excretory
      urography (Figure -1), and renal scintigraphy with 99mTc-DTPA (Figure-2). She was
      submitted to a robotic-assisted right nephropexy with a polypropylene mesh fixing
      the right kidney to the ipsilateral psoas muscle fascia. RESULT: We reported a 96
      minute surgical time. The patient was discharged in the first postoperative day.
      At the one-month follow-up, there was an important improvement of the symptoms,
      with normality renal function and imaging tests describing adequate renal
      positioning. CONCLUSIONS: Robotic-assisted nephropexy is feasible and can be an
      excellent minimally invasive alternative technique for the proposed surgery. We
      reported a shorter hospital stay and a faster postoperative recovery compared
      with the opened procedure.

PMID- 29211401
TI  - Extrarenal Angiomyolipoma: differential diagnosis of retroperitoneal masses.

PMID- 29211402
TI  - Sonographic patterns of Peyronie's disease in patients with absence of palpable
      plaques.
AB  - PURPOSE: Non-palpable isolated septal plaques of the penis are likely present in
      a significant number of patients affected by erectile dysfunction (ED) and penile
      pain without deformity or curvature. The aim of this study was to evaluate the
      ultrasound (US) patterns observed in patients investigated for ED or penile pain
      without curvature. MATERIALS AND METHODS: We reviewed the medical records of 386
      patients who underwent an initial colour-Doppler ultrasonography (CDU) of the
      penis for DE and/or penile pain without curvature. After satisfying inclusion
      criteria, 41 patients were individualized. All patients had a non-palpable plaque
      with involvement of the penile septum. Three US patterns were identified: focal
      hyperecoic thickening of the intercavernosum septum (IS) with acoustic shadow
      (pattern 1), non-calcified thickening (isoechoic or slightly hyperechoic (pattern
      2), and microcalcifications in the IS without associated acoustic shadow (pattern
      3). RESULTS: Patients' mean age was 51.3+/-16.7. ED was the predominant disorder
      in 73.2% of patients, followed by penile pain and length loss in 19.5% and 7.3%
      of patients, respectively. 32(78.1%) patients showed the pattern 1, 6 (14.6%)
      pattern 2, and 3 (7.3%) pattern 3. Plaques size varied from 3 to 13 mm. The
      penile hemodynamic response to CDU reported abnormal findings distally to the
      septal plaques in 20 patients (<25cm/sec). Median left and right cavernosum
      artery flows measured a peak systolic velocity of 31cm/sec and 33 cm/sec,
      respectively. CONCLUSIONS: We believe that an US study with CDU provides a way to
      characterize, localize, and deliver treatment choice in patients with Peyronie's
      Disease.

PMID- 29211403
TI  - The role of fetal-maternal microchimerism as a natural-born healer in integrity
      improvement of maternal damaged kidney.
AB  - PURPOSE: To identify the fetal stem cell (FSC) response to maternal renal injury
      with emphasis on renal integrity improvement and Y chromosome detection in
      damaged maternal kidney. MATERIALS AND METHODS: Eight non-green fluorescent
      protein (GFP) transgenic Sprague- Dawley rats were mated with GFP-positive
      transgenic male rats. Renal damage was induced on the right kidney at gestational
      day 11. The same procedure was performed in eight non-pregnant rats as control
      group. Three months after delivery, right nephrectomy was performed in order to
      evaluate the injured kidney. The fresh perfused kidneys were stained with anti
      GFP antibody. Polymerase chain reaction (PCR) assay was also performed for the Y
      chromosome detection. Cell culture was performed to detect the GFP-positive
      cells. Technetium-99m-DMSA renal scan and single-photon emission computed
      tomography (SPECT) were performed after renal damage induction and 3 months later
      to evaluate the improvement of renal integrity. RESULTS: The presence of FSCs was
      confirmed by immune histochemical staining as well as immunofluorescent imaging
      of the damaged part. Gradient PCR of female rat purified DNA demonstrated the
      presence of Y-chromosome in the damaged maternal kidney. Moreover, the culture of
      kidney cells showed GPF- positive cells by immunofluorescence microscopy. The
      acute renal scar was repaired and the integrity of damaged kidney reached to near
      normal levels in experimental group as shown in DMSA scan. However, no
      significant improvement was observed in control group. CONCLUSION: FSC seems to
      be the main mechanism in repairing of the maternal renal injury during pregnancy
      as indicated by Y chromosome and GFP-positive cells in the sub-cultured medium.

PMID- 29211404
TI  - Management of long segment anterior urethral stricture (>= 8cm) using buccal
      mucosal (BM) graft and penile skin (PS) flap: outcome and predictors of failure.
AB  - PURPOSE: To evaluate the surgical outcome and predictors of failure of
      substitution urethroplasty using either dorsal onlay buccal mucosal (BM) graft or
      ventral onlay penile skin flap (PS) for anterior urethral stricture >= 8cm.
      PATIENTS AND METHODS: Between March 2010 and January 2016, 50 patients with
      anterior urethral stricture >= 8 cm were treated at our hospital. The surgical
      outcome and success rate were assessed. The predictors of failure were analyzed
      using multivariate analysis. Failure was considered when subsequent urethrotomy
      or urethroplasty were needed. RESULTS: Dorsal onlay BM graft was carried out in
      24 patients, while PS urethroplasty in 26 patients. There was no significant
      difference between both groups regarding patients demographics, stricture
      characteristics or follow-up period. One case in the BM group was lost during
      follow- up. Stricture recurrence was detected in 7 (30.4%) patients out of BM
      group while in 6 (23.1%) patients out of PS group (p value= 0.5). No significant
      differences between both groups regarding overall early and late complications
      were observed. Occurrence of early complications and the stricture length were
      the only predictors of failure in univariate analysis, while in multivariate
      analysis the occurrence of early complications was only significant. CONCLUSION:
      On short-term follow-up, both dorsal onlay BM graft and ventral onlay PS flap
      urethroplasty have similar success rates. However, BM graft has a potential
      advantage to reduce operative time and is also technically easier. The surgeon
      should avoid early local complications as they represent a higher risk for
      failure.

PMID- 29211405
TI  - High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent
      prostate cancer: predictors of disease response.
AB  - BACKGROUND: Some men with localized radio-recurrent prostate cancer may benefit
      from salvage high-intensity focused ultrasound (HIFU). Herein, we describe
      oncologic outcomes and predictors of disease response after salvage whole gland
      HIFU from our prospective cohort. MATERIALS AND METHODS: Patients with localized
      radio-recurrent prostate cancer were prospectively enrolled from January 2005 to
      December 2014. Participants had to meet both biochemical and histological
      definitions of recurrence. Exclusion criteria included the receipt of prior
      salvage therapy, presence of metastatic disease, and administration of ADT in the
      6-months prior to enrollment. Participants were treated with a single session of
      whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary
      endpoint was recurrence-free survival (RFS), defined as a composite endpoint of
      PSA progression (Phoenix criteria), receipt of any further salvage therapy,
      receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis
      was used to determine the primary end-point and stratifications were used to
      determine the significance of 6 pre-specified predictors of improved RFS (TRUS
      biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease
      at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and
      receipt of prior hormone therapy). Survival analysis was performed on
      participants with a minimum of 1-year follow-up. RESULTS: Twenty-four
      participants were eligible for study inclusion with a median follow-up of 31.0
      months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3
      months after treatment and median post-HIFU PSA nadir was 0.04ng/ ml. Median 2
      year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 pre-specified
      predictors, an undetectable PSA nadir was the only significant predictor of
      improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant
      underwent an intervention for a urethral stricture. No participants developed
      osteitis pubis or rectourethral fistulae. CONCLUSIONS: Salvage HIFU allows for
      disease control in selected patients with localized radio-recurrent prostate
      cancer. An undetectable PSA nadir serves as an early predictor of disease
      response.

PMID- 29211408
TI  - Breastfeeding mothers' experiences of bedsharing: A qualitative study.
AB  - Many cultures around the world routinely practise bedsharing by the mother-infant
      dyad. Bedsharing in these cultures is believed to ensure a safe and comfortable
      night's sleep for both mother and infant, as well as supporting breastfeeding.
      Nonetheless, this practice is at odds with dominant Western cultural ideals about
      child rearing and is recommended against by public health campaigns regarding
      SIDS. The current qualitative study aimed to explore the lived experiences of
      breastfeeding mothers who bed-shared with their infants in a Western cultural
      setting. In-depth interviews were conducted with six multiparous mothers and were
      analysed using a phenomenological framework. Seven themes were identified,
      including mothers' increased sleep quality and/or quantity, easier infant
      settling and a strong relationship with breastfeeding ease and duration. Given
      that many mothers bed-share, public policies need to be inclusive of this
      practice in order to lessen the likelihood of unsafe bedsharing practices.

PMID- 29211406
TI  - Can preoperative neutrophil lymphocyte ratio predict malignancy in patients
      undergoing partial nephrectomy because of renal mass?
AB  - PURPOSE: To evaluate the importance of preoperative neutrophil lymphocyte ratio
      (NLR) predicting malignancy in patients who undergo partial nephrectomy due to
      renal mass. MATERIALS AND METHODS: Seventy nine patients who underwent open
      partial nephrectomy for renal masses were included in this retrospective study.
      In preoperative routine blood tests, renal ultrasonography and contrast-enhanced
      computed tomography were performed for all patients. Preoperative neutrophil
      lymphocyte ratio were compared in patients with clear cell renal cell carcinoma
      (Group1, 65 patients) and benign lesions (Group 2, 14 patients). The predictive
      ability of NLR was analyzed by ROC curves and Youden Index method was used to
      identify the cut-off value for NLR. RESULTS: The mean age of patients was 59.8+/
      11.7 years in Group1 and 57.4+/-12.6 years in Group 2 (p=0.493). The mean tumor
      size was 3.8+/-1.2 cm in Group 1 and 3.3+/-1.0 cm in Group 2 (p=0.07). The median
      NLR was 2.48 (1.04) in Group 1 and 1.63 (0.96) in Group 2 (p<0.001). The area
      under a ROC curve was 0.799 (p<0.001). CONCLUSIONS: Preoperative neutrophil
      lymphocyte ratio may predict renal masses that can not be distinguished
      radiologically. Our results must be confirmed by large and properly designed
      prospective, randomized trials.

PMID- 29211407
TI  - Long-term results of the implantation of the AMS 800 artificial sphincter for
      post-prostatectomy incontinence: a single-center experience.
AB  - OBJECTIVES: Report the long-term outcomes of the AMS 800 artificial sphincer (AS)
      for the treatment post-prostatectomy incontinence (PPI) in a single center in
      Brazil. MATERIALS AND METHODS: Clinical data from patients who underwent the
      procedure were retrieved from the medical records of individuals with more than 1
      year of follow-up from May 2001 to January 2016. Continence status (number of
      pads that was used), complications (erosion or extrusion, urethral atrophy, and
      infection), malfunctions, and need for secondary implantation were evaluated. The
      relationship between complications and prior or subsequent radiation therapy (RT)
      was also examined. RESULTS: From May 2001 to January 2016, 121 consecutive
      patients underwent AS implantation for PPI at an oncological referral center in
      Brazil. At the last visit, the AS remained implanted in 106 patients (87.6%), who
      reported adequate continence status (maximum of 1 pad/day). Eight-two subjects
      (67.8%) claimed not to be using pads on a regular basis at the final visit
      (completely dry). Revision occurred in 24 patients (19.8%).Radiation therapy (RT)
      for prostate cancer following radical prostatectomy was used in 47 patients
      before or after AS placement. Twelve patients with a history of RT had urethral
      erosion compared with 3 men without RT (p=0.004). CONCLUSION: Considering our
      outcomes, we conclude that AS implantation yields satisfactory results for the
      treatment of PPI and should remain the standard procedure for these patients.
      Radiation therapy is a risk factor for complication.

PMID- 29211409
TI  - Breastfeeding knowledge, attitudes and training amongst Australian community
      pharmacists.
AB  - INTRODUCTION: Pharmacists are one of the most accessible and trusted
      professionals in the Australian health care system and can have a large impact in
      supporting and encouraging breastfeeding. AIM: This study aimed to research the
      knowledge, attitudes and training satisfaction of Australian pharmacists in the
      area of infant nutrition and breastfeeding. DESIGN, SETTING AND PARTICIPANTS: The
      mixed method study involved quantitative data collection via an online survey and
      qualitative data collected via separate semi-structured interviews. All
      registered pharmacists in the Australian Capital Territory and surrounding
      regional areas were eligible. Participants were recruited via emailed information
      sheets and individual onsite recruitment. KEY FINDINGS: Positive attitudes
      towards and a desire to support and advocate for breastfeeding by pharmacists
      were hampered by a lack of knowledge, confidence, training and education.
      CONCLUSIONS AND FUTURE IMPLICATIONS: Government or other non-profit organisations
      can enhance community-based support for breastfeeding, including developing new
      education and training programs for pharmacy students and pharmacists.

PMID- 29211410
TI  - Pushing the Envelope on STEMI Response.
AB  - New findings from the Mission: Lifeline STEMI Systems Accelerator program suggest
      that a regionalized approach to ST-segment elevation myocardial infarctions
      (STEMI) can cut time-to-treatment for patients modestly, thereby improving the
      prospects for better outcomes. The approach encourages hospitals, emergency
      medical services (EMS) and cardiologists in a region to work together to optimize
      treatment and efficiency so that patients in need of percutaneous coronary
      intervention (PCI) receive this care more expeditiously. The research included
      484 hospitals,  1,253 EMS agencies, and nearly 24,000 patients in 16 regions
      across the United States. The goal was to increase the number of STEMI patients
      who receive PCI bed time parameters. Overall,  the percentage of STEMI patients
      receiving PCI in accordance with guidelines improved from 50% to 55% during the
      study period. Key to the Mission: Lifeline approach is a focus on starting the
      clock ticking on time-to-treatment at first medical contact (FMC) as opposed to
      the hospital door, but this requires coordination with EMS and other hospitals.
      Some observers question whether a push for regionalization is worth the effort,
      considering the modest results thus far.

PMID- 29211411
TI  - Using Telemedicine to Address Crowding in the ED.
AB  - Some health systems are piloting telemedicine solutions in the ED to address
      crowding and decrease patient wait times. One new program, implemented at the
      Lisa Perry Emergency Center at New York Presbyterian (NYP) Weill Cornell Medical
      Center in New York, involves offering low-acuity patients the option of visiting
      an off-site physician via telemedicine hookup. Administrators note that the
      approach can get patients in and out of the ED within 30 minutes, and patients
      have thus far been highly satisfied with the approach. However, an earlier
      telemedicine program piloted at the University of San Diego Health System's
      (UCSD) Hillcrest Hospital in 2013 got bogged down due to administrative and
      insurance reimbursement hurdles, although the approach showed enough promise that
      there is interest in restarting the program.  In the NYP program, patients are
      identified as appropriate candidates for the program at triage. They can opt to
      be seen remotely or through traditional means in the ED's fast-track section.
      Administrators note that patients with complex problems requiring extensive
      workups are not suitable for the telemedicine approach. The most challenging
      aspect of implementing a successful telemedicine program in the ED is getting the
      workflows right, according to administrators. An earlier ED-based telemedicine
      program piloted at UCSD ran into difficulties because the model required the
      involvement of two physicians, and some insurers did not want to pay for the
      telemedicine visits. However, patients were receptive.

PMID- 29211412
TI  - A partnership between researchers and breastfeeding advocates to support safe
      alcohol consumption during breastfeeding.
AB  - In 2009 the first national and international guideline providing direction for
      breastfeeding women on drinking alcohol was included in the National Health and
      Medical Research Council Australian guidelines to reduce health risks from
      drinking alcohol. In the absence of an accompanying education campaign for the
      guidelines, the Australian Breastfeeding Association was able to fill this gap
      and work in partnership with a breastfeeding researcher to develop an education
      resource for Australian women that was also a national and international first.
      This commentary outlines the journey of the research that informed the
      development of the resource and the integral involvement of the Australian
      Breastfeeding Association throughout.

PMID- 29211413
TI  - Selection criteria for wet-nurses: Ancient recommendations that survived across
      time.
AB  - This article will describe the content of the key criteria for the selection of
      wet nurses that persisted across time and the authors who transmitted this
      advice. Where relevant, it will include variations, such as additional
      recommendations or a different weighting being given to one or other criterion by
      a particular author. The focus is on the selection of a wet nurse for the
      employer's baby. The factors that led a woman to enter this employment and the
      consequences for her own baby will not be addressed here as they will be
      discussed elsewhere.  The article is an historical one, drawing on primary
      sources, where possible, and important secondary sources.  Guidelines for the
      selection of wet-nurses have existed from antiquity to the early 20th century.
      The key recommendations managed to survive across the centuries because they were
      considered useful by influential ancient and Early Modern and later authors who
      passed them on through copying and translations. It is tempting to assume that
      the prescriptive advice was followed by physicians and mothers. However, the
      discussion will raise doubts about whether the criteria were adhered to by
      physicians and parents, particularly when wet nurses were in scarce supply.

PMID- 29211414
TI  - Training, Drills Pivotal in Mounting Response to Orlando Shooting.
AB  - Emergency providers at Orlando Regional Medical Center in Orlando. FL, faced
      multiple challenges in responding to the worst mass shooting in U.S. history. As
      the scene of the shooting was only three blocks away from the hospital, there was
      little time to prepare when notified that victims would begin arriving shortly
      after 2 a.m. on June 12. Also, fears of a gunman near the hospital briefly put
      the ED on lock down. However, using the incident command system, the hospital was
      able to mobilize quickly, receiving 44 patients, nine of whom died shortly after
      arrival. Administrators note that recent training exercises geared toward a mass
      shooting event facilitated the response and probably saved lives. Patients
      arrived at the hospital in two waves, with the initial surge occurring right
      after the hooting took place around 2 a.m., and the second surge occurring about
      three hours later. At one point, more than 90 patients were in the ED, more than
      half for reasons unrelated to the shooting. Clinicians contended with a much
      higher than usual noise level while treating patients, making it hard to hear
      reports from EMS personnel. Also, treatment had to commence prior to
      identification for some patients who arrived unconscious or unable to speak.
      While surgeons and other key specialists were called into the hospital to address
      identified needs, administrators actually called hospital personnel to tell them
      not to come in unless they were notified. This prevented added management
      hurdles.

PMID- 29211415
TI  - Education Creates Welcoming Environment for Transgender Patients.
AB  - The ED often is the access point of choice for transgender patients who may be
      reluctant to interact with providers. Experts say there is a need for training
      and education of how to present a gender-affirming healthcare environment.
      Recommended steps include a review of policies, along with corresponding changes
      to electronic and paper intake forms to ensure that the language used is
      inclusive of all genders. While blanket discrimination may be declining, experts
      note that some providers are uncertain about how to interact with a transgender
      patient. It's always best to ask patients for their preferred name and pronoun
      and to repeat this exercise every three to six months for return patients, as
      gender identify can be fluid. To ease anxiety for transgender patients, consider
      developing a navigator program that will pair any transgender patient who
      requests the service with a trained advocate who can support and guide the
      patient through the system.

PMID- 29211417
TI  - [BIODIVERSITY OF ACANTHOCEPHALANS (ACANTHOCEPHALA) IN FRESHWATER FISHES OF
      ASIATIC SUB-ARCTIC REGION].
AB  - The analysis of taxonomical and ecological diversity of acanthocephalans in
      fishes ofAsiatic sub-Arctic region freshwaters, summarizing changes in modern
      views on speciescomposition, life cycles, and ecology of background groups of
      these parasites is given.A priority role of studies provided by O. N. Bauer and
      his scientific school in organizationand development of these aspects of
      acanthocephalology is demonstrated. Special attentionis paid to the assessment of
      acanthocephalan biodiversity of the genus Neoechinorhynchus,the background group
      of freshwater fish parasites of the Asiatic sub-Arctic region,and an original key
      for their species is given. The distribution of acanthocephalans of thegenus
      Acanthocephalus in northeastern Asia is analyzed and prospective study of this
      parasitegroup, evolutionary associated with freshwater isopods of the genus
      Asellus as intermediatehosts, is outlined. The absence of documented evidences on
      intermediate hosts ofother background parasites of freshwater fishes in the
      region, acanthocephalans of the genusMetechinorhynchus, is revealed. It is
      assumed that subsequent taxonomic revisions basedboth on morphological and
      molecular genetic studies are necessary for the reliable revealingof species
      composition in each genus of the background acanthocephalans fromfreshwater
      fishes of Northern Asia. Theoretical significance of the study of
      acanthocephalanlife cycles and revealing their natural intermediate hosts for the
      reliable estimation ofstructural and functional organization of their host
      parasite systems in different parts ofthe range is substantiated and the
      possibility of the distribution of taxonomic conclusionsin new territories is
      analyzed. A brief annotated taxonomical list of freshwater acanthocephalansof the
      Asiatic sub-Arctic region is given.

PMID- 29211418
TI  - [NUMBER DISTRIBUTION AND POPULATION STRUCTURE OF PROTEOCEPHALUS LONGICOLLIS
      (ZEDER, 1800) (CESTODA: PROTEOCEPHALIDEA), A PARASITE OF SMELT AND COREGONIDS].
AB  - The spatial structure and seasonal aspects in the number distribution of the
      cestodeProteocephalus longicollis population, maintained by trophic connections
      of specializedplankton-feeders (the vendace Coregonus albula L. and the smelt
      Osmerus eperlanus L.)in the Lake Onego were studied. Differences in the
      distribution of number of cestode populationin host population, size-age
      structure, and pre-reproductive/reproductive stagesratio of the studied parasites
      were revealed. It was demonstrated that the spatial structureof P. longicollis
      was shaped by the specific characteristics of vendace and smelt populationsin the
      Lake Onego. These species possess partially overlapping ecological niches
      anddifferences in the use of food resources, significantly determining the
      infection dynamicsof the examined fish species.

PMID- 29211419
TI  - [RESULTS OF THE STUDY OF GEOGRAPHICAL VARIABILITY OF THE PARASITE FAUNA AND OF
      THE STRUCTURE OF COMPONENT COMMUNITIES OF MINNOW PHOXINUS PHOXINUS (LINNAEUS)
      PARASITES. 2. THE WATER BODIES OF THE NORTHEASTERN EUROPEAN RUSSIA].
AB  - The material was collected according to commonly accepted methods in 1992
      2013from the following sites: the Lake Krivoye (Kolguev Island); Volonga,
      Schapkina, Kolva,More-Yu, Vorkuta, Kara, and Khalmer-Yu Rivers; Lakes Nikaramata
      (the Kara River basin)and Mercempertato (Yamal Peninsula). A total of 436 of the
      minnow Phoxinus phoxinuswith age 1+-3+ were examined. In the examined water
      bodies, excluding the KolvaRiver, the parasite fauna of the minnow is
      impoverished, and, to a greater extent, possessesan occasional character. In
      rivers Kolpina and Shapkina Rivers, component communitiesof minnow parasites are
      mature (balanced, according to Pugachev, 1999). These minnowparasite communities
      consist of three groups of species separated according to the ratio oftheir
      biomasses. In More-Yu, Vorkuta, Kara, and Khalmer-Yu Rivers, and in Lakes
      Nikaramata,and probably, Mercempertato, parasite communities are immature
      (unbalanced).These minnow parasite communities consist of 1-3 groups of species
      separated accordingthe ratio of their biomass. Characteristics of communities
      from the Volonga Riverneed clarification. Associations between the state of the
      described minnow parasite communitiesand their geological age (Quaternary
      history) are traced.324

PMID- 29211420
TI  - Tongue-tie in the newborn: Follow-up in the first 6 months.
AB  - BACKGROUND: Over the last decade, a number of studies have demonstrated that
      early division of tongue-tie (TT) is associated with significant feeding benefits
      to both mother and baby. Notwithstanding, it remains a controversial procedure.
      We examined the breastfeeding outcomes of a cohort of babies at 1-2 weeks (follow
      up 1) and 3-5 months (follow-up 2), post-TT division. METHODS: We undertook a
      cohort study on all mother/baby dyads who had a TT divided at Canberra Hospital
      between 1 July 2013 and 30 June 2014. We contacted the mothers of both follow-up
      groups by telephone, focusing on breastfeeding and maternal pain. RESULTS: Follow
      up 1 consisted of 116/182 (63.7%) of mothers in the study; contacted at 12.4+-7.8
      days post-division. Of these, 107/116 (92.2%) were still breastfeeding, with
      11/15 (73.3%) of the mothers who had ceased breastfeeding before division having
      re-established it at the time of follow-up (p < 0.00l). Additionally, 90/101
      (89.1%) valid responses reported decreased nipple pain following TT division.
      Follow-up 2 consisted of 112/182 (61.5%) of all mothers in the study; contacted
      at 3.7+-1.8 months of age. Of these, 86/112 (76.8%) were still breastfeeding,
      with 11/15 (73.3%) of mothers who had ceased breastfeeding before division having
      re-established it at follow-up (p < 0.001). CONCLUSION: A divided TT was
      associated with benefits at both periods of follow-up. There was (i) an increase
      in overall breastfeeding rates and (ii) a decrease in maternal pain.

PMID- 29211421
TI  - The roles of zinc in lactation.

PMID- 29211422
TI  - [SOME FEATURES OF THE BIOLOGY AND PARASITE FAUNA OF THE ARCTIC CHAR (SALVELINUS
      ALPINUS L.) IN THE LAKE MUSHTALAMPI (NORTHERN KARELIA)].
AB  - The native population of the Arctic char in the Lake Mushtalampi was studied. 
      The dwarf form of the Arctic char inhabiting the lake was revealed. The fish is
      characterized by extremely low growth rate and by early maturation. Twelve
      parasite species were found in the arctic char. The parasite fauna is typical of
      representatives of Salmonidae.  Distinguishing features of this fauna include the
      absence of narrowly specialized char parasite species. High intensity of
      infection with nematodes Philonema oncorhynchi allows estimating the epizootic
      state of the studied char population as insufficient.

PMID- 29211423
TI  - CHANGES IN SPINATION PATTERNS OVER THE COURSE OF METACERCARIAL DEVELOPMENT OF
      DIPLOSTOMUM PSEUDOSPATHACEUM NIEWIADOMSKA, 1984 (TREMATODA, DIPLOSTOMIDAE).
AB  - Metacercarial development of most Diplostomum species including D.
      pseudospathaceumoccurs in the eye lenses of their fish hosts and is accompanied
      by radical morphologicalchanges often referred to as metamorphosis. One of the
      structures undergoing substantialchanges in D. pseudospathacewn are tegumental
      spines. The present study used phalloidinstaining and confocal microscopy to
      examine these changes in D. pseudospathaceumover the course of development from 3
      day-old to infective metacercariae. Although thegeneral pattern of spination
      remained essentially unchanged, most larval spines continuedgrowing in size until
      late in metacercarial development. From day 10 of development, larvalspination
      was gradually replaced by small incipient definitive spines and the
      infectivemetacercariae had only definitive spination. The possible adaptive role
      of spines in developingmetacercariae is discussed.

PMID- 29211424
TI  - [ECOLOGICAL AND PARASITOLOGICAL CHARACTERISTICS OF THE SMALL REDFISH SEBASTES
      VIVIPARUS (PISCES: SCORPAENIDAE)].
AB  - The results of the parasite fauna research represent peculiarities of formation
      and ecological,faunistic and zoogeographical characteristics of parasite fauna of
      the small redfishSebastes viviparus Krayer. 1845. This species is distinguished
      among the other North AtlanticSebastes by the richest fauna of myxosporidians,
      trematodes, nematodes and acanthocephalans.The parasite fauna of S. viviparus is
      formed mainly of boreal species and toa lesser extent of Arctic-boreal species.
      According to the vertical zonality of parasites infishes of the North Atlantic
      they are mainly represented by mesobenthic and epicontinentalspecies. The
      parasite fauna in small redfish possesses significantly more pronounced
      geographicspecificity than that of other North Atlantic Sebastes species.

PMID- 29211425
TI  - [XENOMONITORING OF THE DIROFILARIASIS IN THE SOUTH AND NORTH-WEST OF THE RUSSIAN
      FEDERATION].
AB  - Xenomonitoring (detection of filarial larvae in mosquitoes) of vectors of
      dirofilariasiswas performed in 2009-2013 in vectors collected in southern and
      northwestern regions ofthe Russian Federation. In Rostov, Astrakhan, Krasnodar,
      and Novgorod Provinces and inthe Republic of Adygea the degree of infestation of
      mosquito larvae with Dirofilaria constituted1.8 +/- 0.2 % (66/3590), 0.9 +/- 0.4
      % (4/470), 0.8 +/- 0.2 % (11/1382), 0.7 +/- 0.4 %(3/438), and 0.5 +/- 0.5 %
      (1/190), respectively. Total degree of infestation of mosquitoeswith larvae of
      Dirofilaria spp. constituted 2.3 +/- 0.3 % (45/1936), 1.9 +/- 0.4 % (25/1334),and
      0.6 +/- 0.1 % (15/2713) in Aedes (Meigen, 1818), Culex (Linnaeus, 1758), and
      Anopheles(Meigen, 1818). No microfilariae were found in Culiseta (Felt, 1904)
      (0/87).

PMID- 29211426
TI  - [HEMATOLOGY AND BLOOD CHEMISTRY OF THE HERRING GULL LARUS ARGENTATUS INFESTED BY
      CESTODES DIPHYLLOBOTHRIUM DENDRITICUM (CESTODA: DIPHYLLOBOTHRIIDAE)].
AB  - Hematological and plasma biochemical analyses and parasitological detection
      werecarried out in the herring gull Larus argentatus. Hematological and plasma
      biochemicalparameters in uninfected gulls and gulls infected by Diphyllobothrium
      dendriticum (Cestoda:Diphyllobothriidae) were compared. Hemoglobin content and
      numbers of erythrocyteswere reduced; numbers of leukocytes and sorption capacity
      of erythrocytes wereimproved in blood of the infected herring gulls.
      Hematological index (eosinophil/lymphocyteratio) in infected gulls increased 1.8
      times in comparison with eosinophil/lymphocyteratio in uninfected gulls.
      Metabolic imbalances in herring gulls infected by D. dendriticumwere determined.
      Levels of the total protein, phospholipids, triglyceride, phosphorus,
      calcium,magnesium and sodium, and the activity of alkaline phosphatase decreased
      in plasmablood of infected gulls; at the same time, the content of the uric acid,
      glucose, modifiedalbumin and circulatory immune complex and activities of
      transaminases and lactate dehydrogenasehad increased. It is assumed that the
      obtained results testify to the appearanceof abnormalities in the digestion
      processes and the activity of immune and circulatory systemscaused by the
      invasion of gulls with D. dendriticum.375

PMID- 29211427
TI  - [PHENOLOGY OF MALARIAL MOSQUITOES (DIPTERA, CULICIDAE) AND THEIR EPIDEMIOLOGICAL
      VALUE IN THE SOUTHERN TOMSK PROVINCE].
AB  - The article provides the data on the incidence of malaria in Tomsk Province since
      1935till present. The results of phenological observations of malarial mosquitoes
      (Diptera: Culicidae)performed in 2005-2014 in southern Tomsk Province are given.
      Key dates in lifeof mosquitoes are determined, including the beginning of
      departure from wintering sites,emergence of the first preimaginal stages,
      departure of the first generation of imagoes, thebeginning of the 54rr7yu6t'
      diapause. Terms of the period of possible transfer of malariain southern Tomsk
      Province are retrospectively calculated.

PMID- 29211428
TI  - [THE FAUNA AND POPULATION OF CHEWING LICE (INSECTA, PHTHIRAPTERA) PARASITIZING
      SEDENTARY PASSERINE BIRDS (AVES, PASSERIFORMES) IN YAKUTIA].
AB  - The data on the fauna, abundance and prevalence of chewing lice collected from
      360specimens of 13 sedentary species of passerine birds in Yakutia are given. A
      total of 3206chewing lice specimens belonging to 27 species of 6 genera were
      found. Most exploredbird species were infested with several chewing lice species.
      We assume exchanges of parasitescould take place between some bird species in the
      region explored.

PMID- 29211429
TI  - Training Together: Interdisciplinary MCI drill prepares paramedic and nursing
      students for safe, effective care.

PMID- 29211430
TI  - [EXOSKELETON ABNORMALITIES IN TAIGA TICK FEMALES FROM POPULATIONS OF THE ASIATIC
      PART OF RUSSIA].
AB  - Studies of the phenotypic structure of Ixodes persulcatus (Schulze, 1930)
      populationsin relation to their exoskeleton abnormalities are important in both
      theoretical and practicalrespects. The data on the species' population structure
      in Asiatic part of Russia arefragmentary. The goal of the study was to describe
      taiga tick population structure based onthe pattern of females' exoskeleton
      abnormalities revealed in Asiatic part of Russia.A total of 3872 I. persulcatus
      females from 16 geographically remote sites of Far Eastern,Siberian, and Ural
      Federal Districts (FEFD, SFD, and UFD accordingly) were studied.It was
      demonstrated that all the populations possessed specimens with
      exoskeletonabnormalities. The "shagreen skin" abnormality was dominant in all
      these areas. At the sametime, the percentage of abnormalities among the specimens
      collected to the north of55 degrees N is considerably higher (63.4 +/- 3.39 %)
      than that of samples from the SFD southwardterritories (33.1 +/- 3.43 %). The
      frequency of abnormalities in its turn is lower(24.4 +/- 1.93 %) in the females
      from the territories with moderate monsoon and moderatecontinental climate (FEFD)
      than that in specimens from SFD and UFD areas with sharpcontinental climate.
      Thus, such polymorphism of the females' exoskeleton structure mayreflect the
      natural phenogeographical variability of the character rather than the result
      ofthe anthropogenic impact.403

PMID- 29211431
TI  - [NEW FINDINGS OF RARE SPECIES OF THE MITE GENUS SPINTURNIX VON HEYDEN, 1826
      (MESOSTIGMATA: GAMASINA: SPINTURNICIDAE)IN RUSSIA AND TADJIKISTAN].
AB  - The article reports new findings of rare and poorly known mite species of the
      genusSpinturnix von Heyden, 1826 (Gamasina: Spinturnicidae) parasitizing bats of
      the generaMyotis and Barbastella in Russia and Tadjikistan.

PMID- 29211432
TI  - Hands On: Product Reviews From Street Crews.

PMID- 29211434
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29211433
TI  - Brain Drain: Provide more growth opportunities for paramedics.

PMID- 29211435
TI  - Improved Multiprotein Microcontact Printing on Plasma Immersion Ion Implanted
      Polystyrene.
AB  - Multiprotein micropatterning allows the creation of complex, controlled
      microenvironments for single cells that can be used for the study of the
      localized effects of various proteins and signals on cell survival, development,
      and functions. To enable analysis of cell interactions with microprinted
      proteins, the multiprotein micropattern must have low cross-contamination and
      high long-term stability in a cell culture medium. To achieve this, we employed
      an optimized plasma ion immersion implantation (PIII) treatment to provide
      polystyrene (PS) with the ability to covalently immobilize proteins on contact
      while retaining sufficient transparency and suitable surface properties for
      contact printing and retention of protein activity. The quality and long-term
      stability of the micropatterns on untreated and PIII treated PS were compared
      with those on glass using confocal microscopy. The protein micropattern on the
      PIII treated PS was more uniform and had a significantly higher contrast that was
      not affected by long-term incubation in cell culture media because the proteins
      were covalently bonded to PIII treated PS. The immunostaining of mouse pancreatic
      beta cells interacting with E-cadherin and fibronectin striped surfaces showed
      phosphorylated paxillin concentrated on cell edges over the fibronectin stripes.
      This indicates that multiprotein micropatterns printed on PIII treated PS can be
      used for high-resolution studies of local influence on cell morphology and
      protein production.

PMID- 29211436
TI  - Quantitative Determination of Telomerase Activity by Combining Fluorescence
      Correlation Spectroscopy with Telomerase Repeat Amplification Protocol.
AB  - Telomerase is a key enzyme for maintaining the telomere length and is regarded as
      a versatile cancer biomarker and a potential drug target due to its important
      role in cancer and aging. It is necessary to develop a sensitive and reliable
      method for detection of telomerase activity due to its very low level in cells.
      In this Article, we propose an ultrasensitive and robust method for quantitative
      determination of telomerase activity by combining single molecule fluorescence
      correlation spectroscopy (FCS) with telomerase repeat amplification protocol
      (TRAP). The principle of this new method (FCS-TRAP) is based on measurement of
      the change in characteristic diffusion time and molecule number of TRAP products
      by FCS. The characteristic diffusion time is related to the length of TRAP
      products, and the molecule number represents the concentration of TRAP products.
      We optimized the conditions of TRAP procedure and FCS measurements. We observed
      that the telomerase activities are positively correlated to characteristic
      diffusion time and molecule number of TRAP products at optimal conditions. This
      method was successfully used for determination of telomerase activity of
      different cells, and detection of a single cell was realized. Meanwhile, this
      method was used to evaluate the inhibition efficiency of inhibitors, and the IC50
      values obtained were in good agreement with the references. Compared to current
      TRAP methods, this method shows reliable quantification, ultrahigh sensitivity,
      and short detection time and is without separation. We believe that the FCS-TRAP
      method has a potential application in clinical diagnosis and screening of
      telomerase inhibitors.

PMID- 29211437
TI  - High-Performance Transition Metal Phosphide Alloy Catalyst for Oxygen Evolution
      Reaction.
AB  - Oxygen evolution reaction (OER) is a pivotal process in many energy conversion
      and storage techniques, such as water splitting, regenerative fuel cells, and
      rechargeable metal-air batteries. The synthesis of stable, efficient, non-noble
      metal-based electrocatalysts for OER has been a long-standing challenge. In this
      work, a facile and scalable method to synthesize hollow and conductive iron
      cobalt phosphide (Fe-Co-P) alloy nanostructures using an Fe-Co metal organic
      complex as a precursor is described. The Fe-Co-P alloy exhibits excellent OER
      activity with a specific current density of 10 mA/cm2 being achieved at an
      overpotential as low as 252 mV. The current density at 1.5 V (vs reversible
      hydrogen electrode) of the Fe-Co-P catalyst is 30.7 mA/cm2, which is more than 3
      orders of magnitude greater than that obtained with state-of-the-art Fe-Co oxide
      catalysts. Our mechanistic experiments and theoretical analysis suggest that the
      electrochemical-induced high-valent iron stabilizes the cobalt in a low-valent
      state, leading to the simultaneous enhancement of activity and stability of the
      OER catalyst.

PMID- 29211438
TI  - Atmospheric Pressure Plasma Jet-Assisted Synthesis of Zeolite-Based Low-k Thin
      Films.
AB  - Zeolites are ideal low-dielectric constant (low-k) materials. This paper reports
      on a novel plasma-assisted approach to the synthesis of low-k thin films
      comprising pure-silica zeolite MFI. The proposed method involves treating the
      aged solution using an atmospheric pressure plasma jet (APPJ). The high
      reactivity of the resulting nitrogen plasma helps to produce zeolite crystals
      with high crystallinity and uniform crystal size distribution. The APPJ treatment
      also remarkably reduces the time for hydrothermal reaction. The zeolite MFI
      suspensions synthesized with the APPJ treatment are used for the wet deposition
      to form thin films. The deposited zeolite thin films possessed dense morphology
      and high crystallinity, which overcome the trade-off between crystallinity and
      film quality. Zeolite thin films synthesized using the proposed APPJ treatment
      achieve low leakage current (on the order of 10-8 A/cm2) and high Young's modulus
      (12 GPa), outperforming the control sample synthesized without plasma treatment.
      The dielectric constant of our zeolite thin films was as low as 1.41. The overall
      performance of the low-k thin films synthesized with the APPJ treatment far
      exceed existing low-k films comprising pure-silica MFI.

PMID- 29211439
TI  - Simultaneous Perforation and Doping of Si Nanoparticles for Lithium-Ion Battery
      Anode.
AB  - Silicon nanostructures have served as promising building blocks for various
      applications, such as lithium-ion batteries, thermoelectrics, and solar energy
      conversions. Particularly, control of porosity and doping is critical for fine
      tuning the mechanical, optical, and electrical properties of these silicon
      nanostructures. However, perforation and doping are usually separated processes,
      both of which are complicated and expensive. Here, we demonstrate that the porous
      nano-Si particles with controllable dopant can be massively produced through a
      facile and scalable method, combining ball-milling and acid-etching. Nano-Si with
      porosity as high as 45.8% can be achieved with 9 orders of magnitude of
      conductivity changes compared to intrinsic silicon. As an example for
      demonstration, the obtained nano-Si particles with 45.8% porosity and 3.7 atom %
      doping can serve as a promising anode for lithium-ion batteries with 2000 mA h/g
      retained over 100 cycles at the current density of 0.5 C, excellent rate
      performance with 1600 mA h/g at the current density of 5 C, and a stable cycling
      performance of above 1500 mA h/g retained over 940 cycles at the current density
      of 1 C with carbon coating.

PMID- 29211440
TI  - Gold Nanoparticles Decorated Hematite Photoelectrode for Sensitive and Selective
      Photoelectrochemical Aptasensing of Lysozyme.
AB  - Photoelectrochemical aptasensor (PECAS) is a new and promising detection platform
      with both high sensitivity and good selectivity. Exploration of new
      photoelectrode materials and establishment of effective charge transfer channel
      between photoelectrode and aptamer are the main challenges in this field. In this
      work, an efficient PECAS based on Au nanoparticles (NPs) decorated Fe2O3 nanorod
      photoelectrode is rationally designed, fabricated, and exhibited excellent
      sensitivity and selectivity for detection of lysozyme (Lys) with an ultralow
      detection limit of 3 pM and wide detection range from 10 pM to 100 nM. The Au NPs
      not only act as anchor to establish an efficient charge transfer channel between
      the photoelectrode and the aptamer, but also help to enhance the PEC performance
      through adjusting the carrier density of Fe2O3. The rationally designed
      photoelectrode opens up a distinctive avenue for promoting the PECAS to be a
      versatile analysis method.

PMID- 29211441
TI  - Mechanistic Study of Electrolyte Additives to Stabilize High-Voltage Cathode
      Electrolyte Interface in Lithium-Ion Batteries.
AB  - Current developments of electrolyte additives to stabilize electrode-electrolyte
      interface in lithium-ion batteries highly rely on a trial-and-error search, which
      involves repetitive testing and intensive amount of resources. The lack of
      understandings on the fundamental protection mechanisms of the additives
      significantly increases the difficulty for the transformational development of
      new additives. In this study, we investigated two types of individual protection
      routes to build a robust cathode-electrolyte interphase at high potentials: (i) a
      direct reduction in the catalytic decomposition of the electrolyte solvent; and
      (ii) formation of a "corrosion inhibitor film" that prevents severely attack and
      passivation from protons that generated from the solvent oxidation, even the
      decomposition of solvent cannot be mitigated. Effect of two exemplary electrolyte
      additives, lithium difluoro(oxalato)borate (LiDFOB) and 3-hexylthiophene (3HT),
      on LiNi0.6Mn0.2Co0.2O2 (NMC 622) cathode were investigated to validate our
      hypothesis. It is demonstrated that understandings of both electrolyte additives
      and solvent are essential and careful balance between the cathode protection
      mechanism of additives and their side effects is critical to obtain optimum
      results. More importantly, this study opens up new directions of rational design
      of functional electrolyte additives for the next-generation high-energy-density
      lithium-ion chemistries.

PMID- 29211442
TI  - Atomic Layer Deposition of Nickel on ZnO Nanowire Arrays for High-Performance
      Supercapacitors.
AB  - A novel hybrid core-shell structure of ZnO nanowires (NWs)/Ni as a
      pseudocapacitor electrode was successfully fabricated by atomic layer deposition
      of a nickel shell, and its capacitive performance was systemically investigated.
      Transmission electron microscopy and X-ray photoelectron spectroscopy results
      indicated that the NiO was formed at the interface between ZnO and Ni where the
      Ni was oxidized by ZnO during the ALD of the Ni layer. Electrochemical
      measurement results revealed that the Ti/ZnO NWs/Ni (1500 cycles) electrode with
      a 30 nm thick Ni-NiO shell layer had the best supercapacitor properties including
      ultrahigh specific capacitance (~2440 F g-1), good rate capability (80.5%) under
      high current charge-discharge conditions, and a relatively better cycling
      stability (86.7% of the initial value remained after 750 cycles at 10 A g-1).
      These attractive capacitive behaviors are mainly attributed to the unique core
      shell structure and the combined effect of ZnO NW arrays as short charge transfer
      pathways for ion diffusion and electron transfer as well as conductive Ni serving
      as channel for the fast electron transport to Ti substrate. This high-performance
      Ti/ZnO NWs/Ni hybrid structure is expected to be one of a promising electrodes
      for high-performance supercapacitor applications.

PMID- 29211443
TI  - Broadband Photonic Spin Hall Meta-Lens.
AB  - Meta-lens represents a promising solution for optical communications and
      information processing owing to its miniaturization capability and desirable
      optical properties. Here, spin Hall meta-lens is demonstrated to manipulate
      photonic spin-dependent splitting induced by spin-orbital interaction in
      transverse and longitudinal directions simultaneously at visible wavelengths,
      with low dispersion and more than 90% diffraction efficiency. The broadband
      dielectric spin Hall meta-lens is achieved by integrating two geometric phase
      lenses with different functionalities into one single dynamic phase lens, which
      manifests the ultracompact, portable, and polarization-dependent features. The
      broadband spin Hall meta-lens may find important applications in imaging,
      sensing, and multifunctional spin photonics devices.

PMID- 29211444
TI  - Octahedral-Like CuO/In2O3 Mesocages with Double-Shell Architectures: Rational
      Preparation and Application in Hydrogen Sulfide Detection.
AB  - This contribution describes a facile strategy for constructing octahedral-like
      CuO/In2O3 mesocages with double-shell architectures. The synthetic method
      included first preparation of unifrom Cu2O as an ideal self-sacrificial template
      and then decoration by a In2O3 outer layer through room-temperature Cu2O-engaged
      redox etching reaction combined with subsequent annealing process. Various
      characterization techniques manifested that In2O3 nanoparticles were uniformly
      grown on the surface of CuO mesocages, resulting in a well-defined double-shelled
      heterostructure. When evaluated as a novel sensing material for hydrogen sulfide
      (H2S) detection, the resultant octahedral-like CuO/In2O3 heterostructures
      exhibited obviously enhanced sensing response, lower operating temperature as
      well as faster response/recover speed during the dynamic measurement compared to
      the pristine CuO particles, which is likely related to the high-level of adsorbed
      oxygen concentration, resistance modulation effect, and unique microstructure of
      as-prepared CuO/In2O3 heterostructure.

PMID- 29211445
TI  - Synergistic Effects between Doped Nitrogen and Phosphorus in Metal-Free Cathode
      for Zinc-Air Battery from Covalent Organic Frameworks Coated CNT.
AB  - A covalent organic framework that is composed of hexachlorocyclotriphosphazene
      and dicyanamide has been coated on CNT to prepare metal-free oxygen reduction
      reaction catalyst through thermal polymerization of the Zn-air battery cathode.
      The N,P-codoped nanohybrids have highly porous structure and active synergistic
      effect between graphitic-N and -P, which promoted the electrocatalytic
      performance. The electrocatalysts exhibits remarkable half-wave potential (-0.162
      V), high current density (6.1 mA/cm-2), good stability (83%), and excellent
      methanol tolerance for ORR in alkaline solution. Furthermore, the N,P-codoped
      nanohybrids were used as an air electrode for fabrication of a high performance
      Zn-air battery. The battery achieves a high open-circuit potential (1.53 V) and
      peak power density (0.255 W cm-2). Moreover, the effect of N,P codoping on the
      conjugate carbon system and the synergistic effect between graphitic-N and P have
      been calculated through density functional theory calculations, which are
      essentially in agreement with experimental data.

PMID- 29211446
TI  - Cu/Mn Double-Doped CeO2 Nanocomposites as Signal Tags and Signal Amplifiers for
      Sensitive Electrochemical Detection of Procalcitonin.
AB  - Nanomaterials themselves as redox probes and nanocatalysts have many advantages
      for electrochemical biosensors. However, most nanomaterials with excellent
      catalytic activity cannot be directly used as redox probe to construct
      electrochemical biosensor because the redox signal of these nanomaterials can
      only be obtained in strong acid or alkali solution at high positive or negative
      potential, which greatly limits their applications in biologic assay. In this
      study, Cu/Mn double-doped CeO2 nanocomposite (CuMn-CeO2) was synthesized to use
      as signal tags and signal amplifiers for the construction of electrochemical
      immunosensor for sensitive assay of procalcitonin (PCT). Herein, CuMn-CeO2 not
      only possesses excellent catalytic activity toward H2O2 for signal amplification,
      but also can be directly used as redox probe for electrochemical signal readout
      achieved in neutral mild buffer solution at low positive potential. Importantly,
      since doping Cu, Mn into CeO2 lattice structure can generate extra oxygen
      vacancies, the redox and catalytic performance of obtained CuMn-CeO2 was much
      better than that of pure CeO2, which improves the performance of proposed
      immunosensor. Furthermore, CuMn-CeO2 can be implemented as a matrix for
      immobilizing amounts of secondary antibody anti-PCT by forming ester-like
      bridging between carboxylic groups of Ab2 and CeO2 without extra chemical
      modifications, which greatly simplifies the preparative steps. The prepared
      immunosensor exhibited a wide linear range of 0.1 pg mL-1 to 36.0 ng mL-1 with a
      low detection limit of 0.03 pg mL-1. This study implements nanomaterial
      themselves as redox probes and signal amplifiers and paves a new way for
      constructing electrochemical immunosensor.

PMID- 29211447
TI  - Efficient Removal of Polycyclic Aromatic Hydrocarbons, Dyes, and Heavy Metal Ions
      by a Homopolymer Vesicle.
AB  - It is an important challenge to effectively remove environmental pollutants such
      as polycyclic aromatic hydrocarbons (PAHs), dyes, and heavy metal ions at a low
      cost. Herein, we present a multifunctional homopolymer vesicle self-assembled
      from a scalable homopolymer, poly(amic acid) (PAA), at room temperature. The
      vesicle can efficiently eliminate PAHs, cationic dyes, and heavy metal ions from
      water based on pi-pi stacking, hydrophobic effect, and electrostatic interactions
      with the pollutants. The residual concentrations of PAHs, cationic dyes, and
      heavy metal ions (such as Ni2+) in water are lower than 0.60 and 0.30 parts per
      billion (ppb) and 0.095 parts per million (ppm), respectively, representing a
      promising adsorbent for water remediation. Furthermore, precious metal ions such
      as Ag+ can be recovered into silver nanoparticles by in situ reduction on the
      membrane of PAA vesicles to form a silver nanoparticle/vesicle composite
      (Ag@vesicle) that can effectively catalyze the reduction of toxic pollutants such
      as aromatic nitro-compounds and be recycled for more than ten times.

PMID- 29211448
TI  - Inverted Planar Perovskite Solar Cells with a High Fill Factor and Negligible
      Hysteresis by the Dual Effect of NaCl-Doped PEDOT:PSS.
AB  - The performance of inverted perovskite solar cells is highly dependent on hole
      extraction and surface properties of hole transport layers. To highlight the
      important role of hole transport layers, a facile and simple method is developed
      by adding sodium chloride (NaCl) into poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The average power
      conversion efficiency of the perovskite solar cells prepared on NaCl-doped
      PEDOT:PSS is 17.1% with negligible hysteresis, compared favorably to the control
      devices (15.1%). Particularly, they exhibit markedly improved Voc and fill factor
      (FF), with the best FF as high as 81.9%. The enhancement of photovoltaic
      performance is ascribed to two effects. Better conductivity and hole extraction
      of PEDOT:PSS are observed after NaCl doping. More intriguingly, the perovskite
      polycrystalline film shows a preferred orientation along the (001) direction on
      NaCl-doped PEDOT:PSS, leading to a more uniform thin film. The comparison of the
      crystal structure between NaCl and MAPbCl3 indicates a lattice constant mismatch
      less than 2% and a matched chlorine atom arrangement on the (001) surface, which
      implies that the NaCl crystallites on the top surface of PEDOT:PSS might serve as
      seeds guiding the growth of perovskite crystals. This simple method is fully
      compatible with printing technologies to mass-produce perovskite solar cells with
      high efficiency and tunable crystal orientations.

PMID- 29211449
TI  - Novel Reduced Graphene Oxide/Zinc Silicate/Calcium Silicate Electroconductive
      Biocomposite for Stimulating Osteoporotic Bone Regeneration.
AB  - In the absence of external assistance, autogenous healing of bone fracture is
      difficult due to impaired regeneration ability under osteoporosis pathological
      conditions. In this study, a reduced graphene oxide/zinc silicate/calcium
      silicate (RGO/ZS/CS) conductive biocomposite with an optimal surface
      electroconductivity of 5625 S/m was prepared by a two-step spin-coating method.
      The presence of lamellar apatite nanocrystals on the surfaces of the biocomposite
      suggests that it has good in vitro biomineralization ability. The silicon and
      zinc released from the biocomposite induced a significant increase in the
      osteogenesis of mouse bone mesenchymal stem cells (mBMSCs). Furthermore, alkaline
      phosphatase activities were further promoted when 3 MUA direct current was
      applied to stimulate the mBMSCs that were cultured on the RGO/ZS/CS surface.
      However, electrical stimulation failed to further upregulate the osteogenesis
      related gene expression. Moreover, RGO/ZS/CS extracts were found to suppress the
      receptor activator of nuclear factor-kappaB ligand-induced osteoclastic
      differentiation of mouse leukemic monocyte macrophages (RAW264.7 cells). Although
      the zinc ions in the RGO/ZS/CS extracts showed an inhibitory role in human
      umbilical vein endothelial cell (HUVEC) proliferation, dilutions of the RGO/ZS/CS
      extracts (1/16, 1/32, and 1/64) promoted HUVEC proliferation, and their
      angiogenesis-related gene expression was also upregulated. On the basis of the
      results of the in vitro angiogenesis model, more interconnected tubes formed when
      the above dilutions of RGO/ZS/CS extracts were added to ECMatrix. The new
      RGO/ZS/CS electroconductive biocomposite has potential to be used for stimulating
      osteoporotic bone regeneration.

PMID- 29211450
TI  - Waterproof Narrow-Band Fluoride Red Phosphor K2TiF6:Mn4+ via Facile
      Superhydrophobic Surface Modification.
AB  - With unique and efficient narrow-band red emission and broadband blue light
      absorption characteristics, Mn4+-activated fluoride red phosphors have gained
      increasing attention in warm white LEDs (WLEDs) and liquid crystal display (LCD)
      backlighting applications, whereas the intrinsic hygroscopic nature of these
      phosphors have inevitably limited their practical applications. Herein, a
      waterproof narrow-band fluoride phosphor K2TiF6:Mn4+ (KTF) has been demonstrated
      via a facile superhydrophobic surface-modification strategy. With the use of
      superhydrophobic surface modification with octadecyltrimethoxysilane (ODTMS) on
      KTF surfaces, the moisture-resistance performance and thermal stability of the
      phosphor KTF can be significantly improved. Meanwhile, the absorption, and
      quantum efficiency did not show obvious changes. The surface-modification
      processes and mechanism, as well as moisture-resistance performances and
      luminescence properties, of the phosphors have been carefully investigated. It
      was found that the luminous efficiency (LE) of the modified KTF was maintained at
      83.9% or 84.3% after being dispersed in water for 2 h or aged at high temperature
      (85  degrees C) and high humidity (85%) atmosphere (HTHH) for 240 h,
      respectively. The WLEDs fabricated with modified KTF phosphor showed excellent
      color rendition with lower color temperature (2736 K), higher color rendering
      index (CRI, Ra = 87.3, R9 = 80.6), and high luminous efficiency (LE = 100.6 lm/W)
      at 300 mA. These results indicate that hydrophobic silane coupling agent (SCA)
      surface modification was a promising strategy for enhancing moisture resistance
      of humidity-sensitive phosphors, exhibiting great potential for practical
      applications.

PMID- 29211451
TI  - CLIP6-PNA-Peptide Conjugates: Non-Endosomal Delivery of Splice Switching
      Oligonucleotides.
AB  - Efficient delivery of oligonucleotides still remains a challenge in the field of
      oligonucleotide based therapy. Peptide nucleic acid (PNA), a DNA analogue that is
      typically synthesized by solid phase peptide chemistry, has been conjugated to a
      variety of cell penetrating peptides (CPP) as a means of improving its cellular
      uptake. These CPPs typically deliver their cargoes into cells by an endosomal
      dependent mechanism resulting in lower bioavailability of the cargo. Herein, we
      designed and synthesized PNA-peptide conjugates as splice switching
      oligonucleotides (SSO) targeting the Mnk2 gene, a therapeutic target in cancer.
      In humans, the MKNK2 gene, is alternatively spliced, generating isoforms with
      opposite biological activities: Mnk2a and Mnk2b. It was found that the Mnk2a
      isoform is down-regulated in breast, lung, brain, and colon tumors and is a tumor
      suppressor, whereas MnK2b is oncogenic. We have designed and synthesized PNAs
      that were conjugated to either of the following peptides: a nuclear localization
      sequence (NLS) or a cytosol localizing internalization peptide (CLIP6). CLIP6-PNA
      demonstrates effective cellular uptake and exclusively employs a nonendosomal
      mechanism to cross the cellular membranes of glioblastoma cells (U87). Simple
      incubation of PNA-peptide conjugates in human glioblastoma cells up-regulates the
      Mnk2a isoform leading to cancer cell death.

PMID- 29211452
TI  - Promoted Chondrogenesis of Cocultured Chondrocytes and Mesenchymal Stem Cells
      under Hypoxia Using In-situ Forming Degradable Hydrogel Scaffolds.
AB  - We investigated the effects of different oxygen tension (21% and 2.5% O2) on the
      chondrogenesis of different cell systems cultured in pH-degradable PVA hydrogels,
      including human articular chondrocytes (hACs), human mesenchymal stem cells
      (hMSCs), and their cocultures with a hAC/hMSC ratio of 20/80. These hydrogels
      were prepared with vinyl ether acrylate-functionalized PVA (PVA-VEA) and
      thiolated PVA-VEA (PVA-VEA-SH) via Michael-type addition reaction. The rheology
      tests determined the gelation of the hydrogels was controlled within 2-7 min,
      dependent on the polymer concentrations. The different cell systems were cultured
      in the hydrogel scaffolds for 5 weeks, and the safranin O and GAG assay showed
      that hypoxia (2.5% O2) greatly promoted the cartilage matrix production with an
      order of hAC > hAC/hMSC > hMSC. The real time quantitative PCR (RT-PCR) revealed
      that the hMSC group exhibited the highest hypertrophic marker gene expression
      (COL10A1, ALPL, MMP13) as well as the dedifferentiated marker gene expression
      (COL1A1) under normoxia conditions (21% O2), while these expressions were greatly
      inhibited by coculturing with a 20% amount of hACs and significantly further
      repressed under hypoxia conditions, which was comparative to the sole hAC group.
      The enzyme-linked immunosorbent assay (ELISA) also showed that coculture of
      hMSC/hAC greatly reduced the catabolic gene expression of MMP1 and MMP3 compared
      with the hMSC group. It is obvious that the hypoxia conditions promoted the
      chondrogenesis of hMSC by adding a small amount of hACs, and also effectively
      inhibited their hypotrophy. We are convinced that coculture of hAC/hMSC using in
      situ forming hydrogel scaffolds is a promising approach to producing cell source
      for cartilage engineering without the huge needs of primary chondrocyte harvest
      and expansion.

PMID- 29211453
TI  - Biodegradable Polymer Nanoparticles for Photodynamic Therapy by Bioluminescence
      Resonance Energy Transfer.
AB  - Conventional photodynamic therapy is severely constrained by the limited light
      penetration depth in tissue. Here, we show efficient photodynamic therapy (PDT)
      mediated by bioluminescence resonance energy transfer (BRET) that overcomes the
      light-penetration limitation. The photosensitizer Rose Bengal (RB) was loaded in
      biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which were then
      conjugated with firefly luciferase. Spectroscopic characterizations indicated
      that BRET effectively activated RB to generate reactive oxygen species (ROS). In
      vitro studies of the cellular cytotoxicity and photodynamic effect indicated that
      cancer cells were effectively destroyed by BRET-PDT treatment. In vivo studies in
      a tumor-bearing mouse model demonstrated that tumor growth was significantly
      inhibited by BRET-PDT in the absence of external light irradiation. The BRET
      mediated phototherapy provides a promising approach to overcome the light
      penetration limitation in photodynamic treatment of deep-seated tumors.

PMID- 29211454
TI  - Latent Warheads for Targeted Cancer Therapy: Design and Synthesis of pro
      Pyrrolobenzodiazepines and Conjugates.
AB  - Pyrrolobenzodiazepines (PBDs) and their dimers (bis-PBDs) have emerged as some of
      the most potent chemotherapeutic compounds, and are currently under development
      as novel payloads in antibody-drug conjugates (ADCs). However, when used as stand
      alone therapeutics or as warheads for small molecule drug conjugates (SMDCs),
      dose-limiting toxicities are often observed. As an elegant solution to this
      inherent problem, we designed diazepine-ring-opened conjugated prodrugs lacking
      the imine moiety. Once the prodrug (pro-PBD) conjugate enters a targeted cell,
      cleavage of the linker system triggers the generation of a reactive intermediate
      possessing an aldehyde and aromatic amine. An intramolecular ring-closing
      reaction subsequently takes place as the aromatic amine adds to the aldehyde with
      the loss of water to give the imine and, as a result, the diazepine ring. In our
      pro-PBDs, we mask the aldehyde as a hydrolytically sensitive oxazolidine moiety
      which in turn is a part of a reductively labile self-immolative linker system. To
      prove the range of applications for this new class of latent DNA-alkylators, we
      designed and synthesized several novel latent warheads: pro-PBD dimers and
      hybrids of pro-PBD with other sequence-selective DNA minor groove binders.
      Preliminary preclinical pharmacology studies showed excellent biological activity
      and specificity.

PMID- 29211455
TI  - mRNA-Initiated, Three-Dimensional DNA Amplifier Able to Function inside Living
      Cells.
AB  - DNA molecular machines show great promise in fields such as biomarker discovery
      and biological activity regulation, but operating DNA machines with specific
      functions within living systems remains extremely challenging. Although DNA
      machines have been engineered with exact molecular-level specifications, some
      intrinsic imperfections such as poor cell permeation and fragility in complex
      cytoplasmic milieu persist due to the well-established character of nucleic acid
      molecules. To circumvent these problems, we herein report a molecularly
      engineered, entropy-driven three-dimensional DNA amplifier (EDTD) that can
      operate inside living cells in response to a specific mRNA target. In particular,
      mRNA target/EDTD interaction can specifically initiate an autonomous DNA circuit
      inside living cells owing to the exclusive entropy-driven force, thus providing
      enormous signal amplification for ultrasensitive detection of the mRNA. Moreover,
      owing to molecular engineering of a unique DNA tetrahedral framework into the DNA
      amplifier, EDTD exhibits significantly enhanced biostability and cellular uptake
      efficiency, which are prerequisites for DNA machines used for in vivo
      applications. This programmable DNA machine presents a simple and modular
      amplification mechanism for the detection of intracellular biomarkers. Moreover,
      this study provides a potentially valuable molecular tool for understanding the
      chemistry of cellular systems and offers a design blueprint for further expansion
      of DNA nanotechnology in living systems.

PMID- 29211456
TI  - Ultrastable Gold Nanoparticles Modified by Bidentate N-Heterocyclic Carbene
      Ligands.
AB  - Highly stable gold nanoparticles (Au NPs) functionalized by bidentate N
      heterocyclic carbene (NHC) ligands have been synthesized by top-down and bottom
      up approaches. A detailed study of the effect of alkylation, denticity, and
      method of synthesis has led to the production of NHC-stabilized nanoparticles
      with higher thermal stability than bi- and tridentate thiol-protected Au NPs and
      than monodentate NHC-stabilized NPs. Importantly, bidentate NHC-protected NPs
      also displayed unprecedented stability to external thiol, which has been an
      unsolved problem to date with all nanoparticles. Thus, multidentate NHC ligands
      are an important, and as yet unrecognized, step forward for the preparation of
      high stability nanomaterials.

PMID- 29211457
TI  - 1H NMR Spectroscopy of [FeFe] Hydrogenase: Insight into the Electronic Structure
      of the Active Site.
AB  - The [FeFe] hydrogenase HydA1 from Chlamydomonas reinhardtii has been studied
      using 1H NMR spectroscopy identifying the paramagnetically shifted 1H resonances
      associated with both the [4Fe-4S]H and the [2Fe]H subclusters of the active site
      "H-cluster". The signal pattern of the unmaturated HydA1 containing only [4Fe
      4S]H is reminiscent of bacterial-type ferredoxins. The spectra of maturated
      HydA1, with a complete H-cluster in the active Hox and the CO-inhibited Hox-CO
      state, reveal additional upfield and downfield shifted 1H resonances originating
      from the four methylene protons of the azadithiolate ligand in the [2Fe]H
      subsite. The two axial protons are affected by positive spin density, while the
      two equatorial protons experience negative spin density. These protons can be
      used as important probes sensing the effects of ligand-binding to the catalytic
      site of the H-cluster.

PMID- 29211458
TI  - Dopant-Free Tetrakis-Triphenylamine Hole Transporting Material for Efficient Tin
      Based Perovskite Solar Cells.
AB  - Developing dopant-free hole transporting layers (HTLs) is critical in achieving
      high-performance and robust state-of-the-art perovskite photovoltaics, especially
      for the air-sensitive tin-based perovskite systems. The commonly used HTLs
      require hygroscopic dopants and additives for optimal performance, which adds
      extra cost to manufacturing and limits long-term device stability. Here we
      demonstrate the use of a novel tetrakis-triphenylamine (TPE) small molecule
      prepared by a facile synthetic route as a superior dopant-free HTL for lead-free
      tin-based perovskite solar cells. The best-performing tin iodide perovskite cells
      employing the novel mixed-cation ethylenediammonium/formamidinium with the dopant
      free TPE HTL achieve a power conversion efficiency as high as 7.23%, ascribed to
      the HTL's suitable band alignment and excellent hole extraction/collection
      properties. This efficiency is one of the highest reported so far for tin halide
      perovskite systems, highlighting potential application of TPE HTL material in low
      cost high-performance tin-based perovskite solar cells.

PMID- 29211459
TI  - An Organometallic Cu20 Nanocluster: Synthesis, Characterization, Immobilization
      on Silica, and "Click" Chemistry.
AB  - The development of atomically precise nanoclusters (APNCs) protected by
      organometallic ligands, such as acetylides and hydrides, is an emerging area of
      nanoscience. In principle, these organometallic APNCs should not require harsh
      pretreatment for activation toward catalysis, such as calcination, which can lead
      to sintering. Herein, we report the synthesis of the mixed-valent organometallic
      copper APNC, [Cu20(CCPh)12(OAc)6)] (1), via reduction of Cu(OAc) with Ph2SiH2 in
      the presence of phenylacetylene. This cluster is a rare example of a two-electron
      copper superatom, and the first to feature a tetrahedral [Cu4]2+ core, which is a
      unique "kernel" for a Cu-only superatom. Complex 1 can be readily immobilized on
      dry, partially dehydroxylated silica, a process that cleanly results in release
      of 1 equiv of phenylacetylene per Cu20 cluster. Cu K-edge EXAFS confirms that the
      immobilized cluster 2 is structurally similar to 1. In addition, both 1 and 2 are
      effective catalysts for [3+2] cycloaddition reactions between alkynes and azides
      (i.e., "Click" reactions) at room temperature. Significantly, neither cluster
      requires any pretreatment for activation toward catalysis. Moreover, EXAFS
      analysis of 2 after catalysis demonstrates that the cluster undergoes no major
      structural or nuclearity changes during the reaction, consistent with our
      observation that supported cluster 2 is more stable than unsupported cluster 1
      under "Click" reaction conditions.

PMID- 29211460
TI  - Impact of a Model Soil Microorganism and of Its Secretome on the Fate of Silver
      Nanoparticles.
AB  - Sulfidation is a key process for silver nanoparticles released from consumer
      products in the environment. This study focuses on the impact of a model soil
      microorganism, Bacillus subtilis, on the fate of pristine and already sulfidized
      Ag-NPs. The nanoparticles were incubated with the initial growth medium, isolated
      secretome, and living bacteria, and characterized for their size and morphology,
      agglomeration state, structure, and Ag speciation. No Ag internalization or
      sorption on the cell wall was detected. A partial sulfidation, leading to an Ag
      Ag2S core-shell structure, was observed in the presence of the secretome, and the
      rate limiting step of the reaction was the oxidation of Ag0, and it was favored
      near the crystal dislocations. The sulfidation was complete in the presence of
      the living bacteria and followed an indirect pathway. Both crystalline Ag2S and
      amorphous Ag2S and/or Ag-thiol were identified. At the opposite, the bacteria had
      no impact on Ag2S. These results suggest that microorganisms participate in the
      sulfidation of Ag-NPs in aerobic systems such as unsaturated soils, and thus
      affect the bioavailability of Ag. It is important to take these transformations
      into account during exposure experiments, since they drastically change the
      exposure conditions. Finally, the secretome of B. subtilis might be used for the
      green synthesis of Ag-Ag2S core-shell nanoparticles.

PMID- 29211461
TI  - Quantification of Substitution of Gelatin Methacryloyl: Best Practice and Current
      Pitfalls.
AB  - Cross-linkable gelatin methacryloyl (GM) is widely used for the generation of
      artificial extracellular matrix (ECM) in tissue engineering. However, the
      quantification of modified groups in GM is still an unsolved issue, although this
      is the key factor for tailoring the physicochemical material properties. In this
      contribution, 1H-13C-HSQC NMR spectra are used to gain detailed structural
      information on GMs and of 2-fold modified gelatin containing methacryloyl and
      acetyl groups (GMAs). Distinctive identification of methacrylate, methacrylamide,
      and acetyl groups present in GMs and GMAs revealed an overlap of methacrylamide
      and modified hydroxyproline signals in the 1H NMR spectrum. Considering this, we
      suggest a method to quantify methacrylate and methacrylamide groups in GMs
      precisely based on simple 1H NMR spectroscopy with an internal standard.
      Quantification of acetylation in GMAs is also possible, yet, 2D NMR spectra are
      necessary. The described methods allow direct quantification of modified groups
      in gelatin derivatives, making them superior to other, indirect methods known so
      far.

PMID- 29211462
TI  - The Eponymous Cofactors in Cytochrome P460s from Ammonia-Oxidizing Bacteria Are
      Iron Porphyrinoids Whose Macrocycles Are Dibasic.
AB  - The enzymes hydroxylamine oxidoreductase and cytochrome (cyt) P460 contain
      related unconventional "heme P460" cofactors. These cofactors are unusual in
      their inclusion of nonstandard cross-links between amino acid side chains and the
      heme macrocycle. Mutagenesis studies performed on the Nitrosomonas europaea cyt
      P460 that remove its lysine-heme cross-link show that the cross-link is key to
      defining the spectroscopic properties and kinetic competence of the enzyme.
      However, exactly how this cross-link confers these features remains unclear. Here
      we report the 1.45 A crystal structure of cyt P460 from Nitrosomonas sp. AL212
      and conclude that the cross-link does not lead to a change in hybridization of
      the heme carbon participating in the cross-link but rather enforces structural
      distortions to the macrocycle away from planarity. Time-dependent density
      functional theory coupled to experimental structural and spectroscopic analysis
      suggest that this geometric distortion is sufficient to define the spectroscopic
      properties of the heme P460 cofactor and provide clues toward establishing a
      relationship between heme P460 electronic structure and function.

PMID- 29211463
TI  - Direct Detection of Multiple Acidic Proton Sites in Zeolite HZSM-5.
AB  - Direct observation of multiple reactive sites in the zeolite HZSM-5, a member of
      the MFI family of zeolite structures, contradicts the traditional view of only
      one type of active protonic species in industrially important zeolites. In
      addition to the well-known Bronsted acid site proton, two other protonic species
      undergo room-temperature hydrogen-deuterium exchange with an alkane hydrocarbon
      reagent, including one zeolite moiety characterized by a broad 1H chemical shift
      at ca. 12-15 ppm that is reported here for the first time. Although the ca. 13
      ppm chemical shift value is consistent with computational predictions from the
      literature for a surface-stabilized hydroxonium ion in a zeolite, data suggest
      that the signal does not arise from hydroxonium species but rather from hydroxyls
      on extra-lattice aluminol species proximate to Bronsted lattice sites, i.e., a
      small population of highly deshielded acid sites. Double-resonance experiments
      show that this species is proximate to Al atoms, similar to the Bronsted acid
      site proton. These sites can be removed by appropriate postsynthesis chemical
      treatment, yielding a catalyst with reduced activity for isotopic H/D exchange
      reactions. Additionally, other extra-lattice aluminum hydroxyl groups previously
      discussed in the literature but whose protons were considered unreactive are also
      shown for the first time to react with hydrocarbon probe molecules. Two
      dimensional exchange NMR reveals direct proton exchange between the Bronsted site
      and these two types of extra-lattice Al-OH species, and it also reveals
      unexpected proton exchange between extra-lattice Al-OH species and an alkane
      reagent.

PMID- 29211464
TI  - The Case Against Charge Transfer Interactions in Dissolved Organic Matter
      Photophysics.
AB  - The optical properties of dissolved organic matter influence chemical and
      biological processes in all aquatic ecosystems. Dissolved organic matter optical
      properties have been attributed to a charge-transfer model in which donor
      acceptor complexes play a primary role. This model was evaluated by measuring the
      absorbance and fluorescence response of organic matter isolates to changes in
      solvent temperature, viscosity, and polarity, which affect the position and
      intensity of spectra for known donor-acceptor complexes of organic molecules.
      Absorbance and fluorescence spectral shape were largely unaffected by these
      changes, indicating that the distribution of absorbing and emitting species was
      unchanged. Overall, these results call into question the wide applicability of
      the charge-transfer model for explaining organic matter optical properties and
      suggest that future research should explore other models for dissolved organic
      matter photophysics.

PMID- 29211465
TI  - Gene Coexpression Networks Drive and Predict Reproductive Effects in Daphnia in
      Response to Environmental Disturbances.
AB  - Increasing effects of anthropogenic stressors and those of natural origin on
      aquatic ecosystems have intensified the need for predictive and functional models
      of their effects. Here, we use gene expression patterns in combination with
      weighted gene coexpression networks and generalized additive models to predict
      effects on reproduction in the aquatic microcrustacean Daphnia. We developed
      models to predict effects on reproduction upon exposure to different
      cyanobacteria, different insecticides and binary mixtures of cyanobacteria and
      insecticides. Models developed specifically for groups of stressors (e.g., either
      cyanobacteria or insecticides) performed better than general models developed on
      all data. Furthermore, models developed using in silico generated mixture gene
      expression profiles from single stressor data were able to better predict effects
      on reproduction compared to models derived from the mixture exposures themselves.
      Our results highlight the potential of gene expression data to quantify effects
      of complex exposures at higher level organismal effects without prior mechanistic
      knowledge or complex exposure data.

PMID- 29211466
TI  - Identification of Unknown Antiandrogenic Compounds in Surface Waters by Effect
      Directed Analysis (EDA) Using a Parallel Fractionation Approach.
AB  - Among all the nuclear-receptor mediated endocrine disruptive effects,
      antiandrogenicity is frequently observed in aquatic environments and may pose a
      risk to aquatic organisms. Linking these effects to responsible chemicals is
      challenging and a great share of antiandrogenic activity detected in the
      environment has not been explained yet. To identify drivers of this effect at a
      hot spot of antiandrogenicity in the German river Holtemme, we applied effect
      directed analysis (EDA) including a parallel fractionation approach, a downscaled
      luciferase reporter gene cell-based anti-AR-CALUX assay and LC-HRMS/MS nontarget
      screening. We identified and confirmed the highly potent antiandrogen 4-methyl-7
      diethylaminocoumarin (C47) and two derivatives in the active fractions. The
      relative potency of C47 to the reference compound flutamide was over 5.2, whereas
      the derivatives were less potent. C47 was detected at a concentration of 13.7
      MUg/L, equal to 71.4 MUg flutamide equivalents per liter (FEq/L) in the
      nonconcentrated water extract that was posing an antiandrogenic activity equal to
      45.5 (+/-13.7 SD) FEq/L. Thus, C47 was quantitatively confirmed as the major
      cause of the measured effect in vitro. Finally, the antiandrogenic activity of
      C47 and one derivate was confirmed in vivo in spiggin-gfp Medaka. An endocrine
      disrupting effect of C47 was observed already at the concentration equal to the
      concentration in the nonconcentrated water extract, underlining the high risk
      posed by this compound to the aquatic ecosystem. This is of some concern since
      C47 is used in a number of consumer products indicating environmental as well as
      human exposure.

PMID- 29211467
TI  - Toward Direct Protein S-Persulfidation: A Prodrug Approach That Directly Delivers
      Hydrogen Persulfide.
AB  - A general strategy of delivering hydrogen persulfide (H2S2) is described herein.
      Esterase- and phosphatase-sensitive H2S2 prodrugs with tunable release rates have
      been synthesized. Their utility is validated in examining protein S
      persulfidation. With this unique approach of directly delivering H2S2, our
      findings reaffirmed that S-persulfidation leads to decreased activity of
      glyceraldehyde 3-phosphate dehydrogenase. This new approach complements available
      prodrugs/donors that directly deliver a single species, including hydrogen
      sulfide, perthiol, and COS, and will be very useful as part of the toolbox for
      delineating the mechanisms of sulfur signaling.

PMID- 29211468
TI  - Visualizing Intercellular Tensile Forces by DNA-Based Membrane Molecular Probes.
AB  - Mechanical forces play critical roles in collective cell behaviors such as cell
      migration, proliferation, and differentiation. Extensive efforts have been made
      to measure forces between cells and extracellular matrices. However, force
      studies at cell-cell junctions remain a challenge. Herein, we reported a novel
      strategy to construct membrane DNA tension probes to visualize tensile forces at
      cell junctions. These lipid-modified probes can self-assemble onto cell membranes
      with high efficiency and stability. Upon experiencing tensile forces generated by
      neighboring cells, unfolding of the probes leads to a large increase in the
      fluorescence intensity. Compatible with readily accessible fluorescence
      microscopes, these easy-to-use membrane DNA tension probes can be broadly used to
      measure intercellular tensile forces.

PMID- 29211469
TI  - Machine Learning of Dynamic Electron Correlation Energies from Topological Atoms.
AB  - We present an innovative method for predicting the dynamic electron correlation
      energy of an atom or a bond in a molecule utilizing topological atoms. Our
      approach uses the machine learning method Kriging (Gaussian Process Regression
      with a non-zero mean function) to predict these dynamic electron correlation
      energy contributions. The true energy values are calculated by partitioning the
      MP2 two-particle density-matrix via the Interacting Quantum Atoms (IQA)
      procedure. To our knowledge, this is the first time such energies have been
      predicted by a machine learning technique. We present here three important proof
      of-concept cases: the water monomer, the water dimer, and the van der Waals
      complex H2...He. These cases represent the final step toward the design of a full
      IQA potential for molecular simulation. This final piece will enable us to
      consider situations in which dispersion is the dominant intermolecular
      interaction. The results from these examples suggest a new method by which
      dispersion potentials for molecular simulation can be generated.

PMID- 29211470
TI  - A Dipolar Cycloaddition Reaction To Access 6-Methyl-4,5,6,7-tetrahydro-1H
      [1,2,3]triazolo[4,5-c]pyridines Enables the Discovery Synthesis and Preclinical
      Profiling of a P2X7 Antagonist Clinical Candidate.
AB  - A single pot dipolar cycloaddition reaction/Cope elimination sequence was
      developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine
      P2X7 antagonists that contain a synthetically challenging chiral center. The
      structure-activity relationships of the new compounds are described. Two of these
      compounds, (S)-(2-fluoro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-6
      methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone
      (compound 29) and (S)-(3-fluoro-2-(trifluoromethyl)pyridin-4-yl)(1-(5
      fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5
      c]pyridin-5-yl)methanone (compound 35), were found to have robust P2X7 receptor
      occupancy at low doses in rat with ED50 values of 0.06 and 0.07 mg/kg,
      respectively. Compound 35 had notable solubility compared to 29 and showed good
      tolerability in preclinical species. Compound 35 was chosen as a clinical
      candidate for advancement into phase I clinical trials to assess safety and
      tolerability in healthy human subjects prior to the initiation of proof of
      concept studies for the treatment of mood disorders.

PMID- 29211471
TI  - A Rejection Scheme for Off-Lattice Kinetic Monte Carlo Simulation.
AB  - We introduce a new kinetic Monte Carlo (KMC) algorithm for off-lattice
      simulation. In off-lattice KMC, one needs to calculate the rates for all possible
      moves from the current state by searching the energy landscape for index 1 saddle
      points surrounding the current basin of attraction. We introduce a rejection
      scheme in which the true rates are replaced by rate estimates. This is done by
      first associating each saddle point with the atom that would move the most if
      that transition were to take place and then constructing an estimate for the
      total rate associated with each atom by using a nearest-neighbor bond count.
      These estimates allow one to select a set of possible transitions, one of which
      is accepted or rejected on the basis of a localized saddle point search focused
      on a particular atom. In principle, this allows a performance boost that scales
      with the number of particles in the system. We test the method on a growing two
      species nanocluster and find we can reduce the computation time by 90% for
      clusters that contain ~55 particles and 96% for clusters that contain ~65
      particles.

PMID- 29211472
TI  - Tuning the Viscoelastic-Gel Transition of Single-Wall Carbon Nanotubes Embedded
      in pH-Responsive Polyelectrolyte Solutions.
AB  - We present the detailed rheological changes that occur when small quantities of
      single-wall carbon nanotubes are dispersed in a poly(acrylic acid) water
      solution, around the overlap polymer concentration, up to the gel point. Here, pH
      is used to tune the gel formation. Suspensions of nanotubes at pH <= 5 are
      exfoliated and dispersed by the polymer. Contacts between the nanotubes are
      mainly through polymer entangling, and the suspension is viscoelastic. At pH > 5,
      the polymer is charged, and the solution is not a good solvent for the nanotubes
      anymore. Nanotube bundles covered with polymer are formed and mechanically
      percolate along the fluid until they become arrested. As a consequence, the
      rheological behavior is dominated by a mesoscale superstructure formed by
      nanotubes and polymer, where viscoelasticity is lost and the suspension becomes
      elastic. At pH >= 9, the surroundings for the nanotubes are worse, bundles and
      flocs grow to a larger extent, and they can be observable by scanning
      microscopies. When the suspension becomes a critical gel, the relaxation moduli
      can be modeled by a power law in the frequency domain in agreement with the model
      developed by Winter and co-workers.

PMID- 29211473
TI  - Comment on "Natural Bond Orbitals and the Nature of the Hydrogen Bond".

PMID- 29211474
TI  - Reply to "Comment on 'Natural Bond Orbitals and the Nature of the Hydrogen
      Bond'".

PMID- 29211475
TI  - Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors
      Using Ligand and Property-Based Design Strategies: Identification of Development
      Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl
      2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF
      06821497).
AB  - A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and
      physicochemical-property-based strategies to address metabolic stability and
      thermodynamic solubility issues associated with previous lead compound 1. The new
      inhibitors incorporated an sp3 hybridized carbon atom at the 7-position of the
      lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole
      group. This transformation enabled optimization of the physicochemical properties
      and potency compared to compound 1. Analysis of relationships between calculated
      log D (clogD) values and in vitro metabolic stability and permeability parameters
      identified a clogD range that afforded an increased probability of achieving
      favorable ADME data in a single molecule. Compound 23a exhibited the best overlap
      of potency and pharmaceutical properties as well as robust tumor growth
      inhibition in vivo and was therefore advanced as a development candidate (PF
      06821497). A crystal structure of 23a in complex with the three-protein PRC2
      complex enabled understanding of the key structural features required for optimal
      binding.

PMID- 29211476
TI  - Applying Machine Learning to Vibrational Spectroscopy.
AB  - The low-energy region of the potential energy surface (PES) of the protonated
      phenylalanine/serine dimer is mapped using the basin-hoping search algorithm, and
      37 isomers are identified within 180 kJ.mol-1 of the global-minimum structure.
      Cluster structures are grouped using hierarchical clustering to partition the PES
      in terms of nuclear configuration. Calculated IR spectra for the various isomers
      are then compared with the isomer-specific IR spectra by means of the cosine
      distance metric to facilitate spectral assignment and identify which regions of
      the PES are populated in the electrospray ionization process.

PMID- 29211477
TI  - Titanium(III)-Oxo Clusters in a Metal-Organic Framework Support Single-Site
      Co(II)-Hydride Catalysts for Arene Hydrogenation.
AB  - Titania (TiO2) is widely used in the chemical industry as an efficacious catalyst
      support, benefiting from its unique strong metal-support interaction. Many
      proposals have been made to rationalize this effect at the macroscopic level, yet
      the underlying molecular mechanism is not understood due to the presence of
      multiple catalytic species on the TiO2 surface. This challenge can be addressed
      with metal-organic frameworks (MOFs) featuring well-defined metal oxo/hydroxo
      clusters for supporting single-site catalysts. Herein we report that the Ti8(MU2
      O)8(MU2-OH)4 node of the Ti-BDC MOF (MIL-125) provides a single-site model of the
      classical TiO2 support to enable CoII-hydride-catalyzed arene hydrogenation. The
      catalytic activity of the supported CoII-hydride is strongly dependent on the
      reduction of the Ti-oxo cluster, definitively proving the pivotal role of TiIII
      in the performance of the supported catalyst. This work thus provides a
      molecularly precise model of Ti-oxo clusters for understating the strong metal
      support interaction of TiO2-supported heterogeneous catalysts.

PMID- 29211478
TI  - Ultrafast Electron Transfer across a Nanocapsular Wall: Coumarins as Donors,
      Viologen as Acceptor, and Octa Acid Capsule as the Mediator.
AB  - Results of our study on ultrafast electron transfer (eT) dynamics from coumarins
      (coumarin-1, coumarin-480, and coumarin-153) incarcerated within octa acid (OA)
      capsules as electron donors to methyl viologen dissolved in water as acceptor are
      presented. Upon photoexcitation, coumarin inside the OA capsule transfers an
      electron to the acceptor electrostatically attached to the capsule leading to a
      long-lived radical-ion pair separated by the OA capsular wall. This charge
      separated state returns to the neutral ground state via back electron transfer on
      the nanosecond time scale. This system allows for ultrafast electron transfer
      processes through a molecular wall from the apolar capsular interior to the
      highly polar (aqueous) environment on the femtosecond time scale. Employing
      femtosecond transient absorption spectroscopy, distinct rates of both forward (1
      25 ps) and backward eT (700-1200 ps) processes were measured. Further
      understanding of the energetics is provided using Rehm-Weller analysis for the
      investigated photoinduced eT reactions. The results provide the rates of the eT
      across a molecular wall, akin to an isotropic solution, depending on the standard
      free energy of the reaction. The insights from this work could be utilized in the
      future design of efficient electron transfer processes across interfaces
      separating apolar and polar environments.

PMID- 29211479
TI  - Molecular Level Understanding of Sodium Dodecyl Sulfate (SDS) Induced Sol-Gel
      Transition of Pluronic F127 Using Fisetin as a Fluorescent Molecular Probe.
AB  - The thermoreversible sol-gel transition of pluronic F127 is markedly altered even
      with addition of submicellar concentration of sodium dodecyl sulfate (SDS)
      surfactant. Multiple fluorescence parameters like fluorescence intensity,
      fluorescence anisotropy and fluorescence lifetime of both the prototropic forms
      (anion (A-*) and phototautomer FT*) of the photoprototropic fluorescent probe
      fisetin has been efficiently used to understand the molecular level properties
      like polarity and microviscosity of the PF127-SDS system as a function of
      temperature. The SDS-induced increase in the interfacial hydrophobicity level is
      seen to affect the sol-gel phase transition of PF127 (21-18  degrees C). The
      ET(30) polarity parameter value of anionic emission of fisetin suggests that
      there is a considerable decrease in the polarity of the PF127 medium with
      increase in temperature and with the addition of SDS. The microviscosity
      progressively increases from ~5 mPa s (sol state, 10  degrees C) to ~22.01 mPa s
      (gel state 35  degrees C) in aqueous solution of PF127. The variation in
      microviscosity with addition of SDS in PF127-SDS mixed system is significant in
      sol phase whereas in gel phase this variation is significantly less. Temperature
      dependent fluorescence lifetime of FT* indicates that there is heterogeneity in
      distribution of fisetin molecules at different domains of PF127. This work also
      show-cases the sensitivity of fisetin toward change in polarity and change in sol
      gel transition temperature of copolymer PF127 with variation in temperature (both
      forward and reverse directions) and SDS.

PMID- 29211480
TI  - Design of Small Molecule Autophagy Modulators: A Promising Druggable Strategy.
AB  - Autophagy is a lysosome-dependent mechanism of intracellular degradation for
      maintaining cellular homeostasis. Dysregulation of autophagy has been verified to
      be closely linked to a number of human diseases. Consequently, targeting
      autophagy has been highlighted as a novel therapeutic strategy for clinical
      utility. Mounting efforts have been done in recent years to elucidate the
      mechanisms of autophagy regulation and to identify potential modulators of
      autophagy. However, most of the compounds target complex and multifaceted pathway
      and proteins, which may limit the evaluation of therapeutic value and in depth
      studies as chemical tools. Therefore, the development of specific and active
      autophagy modulators becomes most desirable. Here, we briefly review the
      regulation of autophagy and then summarize the recent development of small
      molecules targeting the core autophagic machinery. Finally, we put forward our
      viewpoints on the current problems, with the aim to provide reference for future
      drug discovery and potential therapeutic perspectives on novel, potent, selective
      autophagy modulators.

PMID- 29211481
TI  - Asymmetric Synthesis of Rupestonic Acid and Pechueloic Acid.
AB  - In this report, the originally proposed rupestonic acid (5) and pechueloic acid
      (3) were efficiently synthesized. The chiral lactone 13, recycled from the
      degradation of saponin glycosides, was utilized to prepare the key chiral
      fragment 11. During the exploration of this convergent assembly strategy, the
      ring-closing metathesis (RCM), SmI2-prompted intermolecular addition, and [2,3]
      Wittig rearrangement proved to be effective transformations for the synthesis of
      subunits.

PMID- 29211482
TI  - Oriented Attachment Is a Major Control Mechanism To Form Nail-like Mn-Doped ZnO
      Nanocrystals.
AB  - Here, we present a controlled synthesis of Mn-doped ZnO nanoparticles (NPs) with
      predominantly nail-like shapes, whose formation occurs via tip-to-base-oriented
      attachment of initially formed nanopyramids, followed by leveling of sharp edges
      that lead to smooth single-crystalline "nails". This shape is prevalent in
      noncoordinating solvents such as octadecene and octadecane. Yet, the double bond
      in the former promotes oriented attachment. By contrast, Mn-doped ZnO NP
      synthesis in a weakly coordinating solvent, benzyl ether, results in dendritic
      structures because of random attachment of initial NPs. Mn-doped ZnO NPs possess
      a hexagonal wurtzite structure, and in the majority of cases, the NP surface is
      enriched with Mn, indicating a migration of Mn2+ ions to the NP surface during
      the NP formation. When the NP formation is carried out without the addition of
      octadecyl alcohol, which serves as a surfactant and a reaction initiator, large,
      concave pyramid dimers are formed whose attachment takes place via basal planes.
      UV-vis and photoluminescence spectra of these NPs confirm the utility of
      controlling the NP shape to tune electro-optical properties.

PMID- 29211483
TI  - Bidirectional Correlation between Mechanics and Electrochemistry of Poly(vinyl
      alcohol)-Based Gel Polymer Electrolytes.
AB  - The electrochemical-mechanical coupling property of solid electrolyte membranes
      is critical to improving the performance of solid-state energy storage devices. A
      new phenomenon was observed in which the electrochemical charge-discharge process
      induced aligned wrinkles on the edge of poly(vinyl alcohol)-H2SO4 gel polymer
      electrolytes (GPEs), which is attributed to the deformation of polymer chains
      under electrochemical stimulation according to multiscale simulations. In the
      reverse direction, by means of modeling and testing, it was proved that the ionic
      conductivity of GPEs can be tuned by mediating the mechanical properties of GPEs
      via tailoring the polymer at the nanoscale. This bidirectional correlation
      reveals the coupling mechanisms between mechanical and electrochemical properties
      of GPEs and provides an insightful understanding of the origin and regulation of
      the ionic conductivity of GPEs, which is fundamental to improving the performance
      of GPEs.

PMID- 29211484
TI  - Correction to "Aescin Incorporation and Nanodomain Formation in DMPC Model
      Membranes".

PMID- 29211485
TI  - Surface Characterization and Platelet Adhesion on Thin Hydrogel Films of
      Poly(vinyl ether).
AB  - Poly(vinyl ether), with short oxyethylene side chains which possess a simple and
      relatively polar structure, should be a unique candidate for a bioinert material
      thanks to its solubility in water. On the basis of living cationic
      copolymerization and subsequent ultraviolet light irradiation, thin films of
      poly(2-methoxyethyl vinyl ether) with different cross-linking densities were
      prepared on solid substrates. The films were thickened in water, and the extent
      was dependent on the cross-linking density. Although the surface chemistry and
      aggregation states were almost identical to one another, the stiffness, or the
      softness, of the outermost region in the film was strongly dependent on the cross
      linking density. That is, the interface between polymer and water became thicker,
      or more diffused, with decreasing cross-linking density. The blood compatibility
      based on the platelet adhesion on to the hydrogel films was better for a more
      diffused interface.

PMID- 29211486
TI  - Adsorption on Nanopores of Different Cross Sections Made by Electron Beam
      Nanolithography.
AB  - Adsorption on nanoporous matrices is characterized by a pronounced hysteresis
      loop in the adsorption isotherm, when the substrate is loaded and unloaded with
      adsorbate, the origin of which is a matter of immense debate in the literature.
      In this work, we report a study of argon adsorption at 85 K on nonconnecting
      nanopores with one end closed to the surrounding where the effects of different
      pore cross sections fabricated by electron beam lithography (EBL) are
      investigated. A polymethylmethacrylate (PMMA) resist is deposited on the
      electrodes of a sensitive quartz crystal microbalance without degradation of the
      resonance quality factor or the long-term and short-term stabilities of the
      device even at cryogenic temperatures. Four different pores' cross sections:
      circular, square, rectangular, and triangular, are produced from EBL, and the
      isotherms for these pore shapes exhibit pronounced hysteresis loops whose
      adsorption and desorption branches are nearly vertical and have almost the same
      slopes. No difference is observed in the hysteresis loops of the isotherms for
      the pores with triangular and square cross sections, whereas the hysteresis loop
      for the pore with circular cross sections is much narrower, suggesting that they
      are more regular than the other pores. All of these observations suggest that the
      hysteresis behavior resulted mainly from microscopic geometric irregularities
      present in these porous matrices.

PMID- 29211487
TI  - Lattice-Matched Epitaxial Graphene Grown on Boron Nitride.
AB  - Lattice-matched graphene on hexagonal boron nitride is expected to lead to the
      formation of a band gap but requires the formation of highly strained material
      and has not hitherto been realized. We demonstrate that aligned, lattice-matched
      graphene can be grown by molecular beam epitaxy using substrate temperatures in
      the range 1600-1710  degrees C and coexists with a topologically modified moire
      pattern with regions of strained graphene which have giant moire periods up to
      ~80 nm. Raman spectra reveal narrow red-shifted peaks due to isotropic strain,
      while the giant moire patterns result in complex splitting of Raman peaks due to
      strain variations across the moire unit cell. The lattice-matched graphene has a
      lower conductance than both the Frenkel-Kontorova-type domain walls and also the
      topological defects where they terminate. We relate these results to theoretical
      models of band gap formation in graphene/boron nitride heterostructures.

PMID- 29211488
TI  - Simultaneous Detection of H and D NMR Signals in a Micro-Tesla Field.
AB  - We present NMR spectra of remote-magnetized deuterated water, detected in an
      unshielded environment by means of a differential atomic magnetometer. The
      measurements are performed in a MUT field, while pulsed techniques are applied
      following the sample displacement-in a 100 MUT field, to tip both D and H nuclei
      by controllable amounts. The broad-band nature of the detection system enables
      simultaneous detection of the two signals and accurate evaluation of their decay
      times. The outcomes of the experiment demonstrate the potential of ultra-low
      field NMR spectroscopy in important applications where the correlation between
      proton and deuteron spin-spin relaxation rates as a function of external
      parameters contains significant information.

PMID- 29211489
TI  - Pregnancies and live births, active component service women, U.S. Armed Forces,
      2012-2016.
AB  - This report summarizes data on the demographic and military characteristics of
      women and women of childbearing potential (WOCBP) in the active component of the
      U.S. Armed Forces during 2012-2016. Data on pregnancy-related care and birth
      rates are also presented. In 2016, WOCBP comprised the vast majority of active
      component service women. The largest proportions of WOCBP were in the categories
      of women who were 20-24 years old, non-Hispanic white, junior enlisted rank, and
      in a communications/intelligence occupation. WOCBP were roughly equally
      distributed in the Army, Navy, and Air Force, whereas only 7.5% served in the
      Marine Corps. Slightly more than one-quarter of WOCBP had ever deployed to the
      U.S. Central Command area of responsibility (CENTCOM AOR). In 2016, 13.1% of all
      WOCBP had at least one pregnancy-related event and 1.1% of deployed WOCBP had a
      pregnancy event during a deployment to CENTCOM AOR. The prevalence of pregnancy
      decreased slightly over the surveillance period. There were 63,879 live births
      during the surveillance period, for an overall live birth rate of 64.9 live
      births per 1,000 person-years (p-yrs). This rate of live births decreased
      steadily from 69.8 per 1,000 p-yrs in 2012 to 59.7 per 1,000 p-yrs in 2016. Rates
      of live births were highest among women who were 30-34 years old, enlisted or
      junior officer rank, Army, in healthcare occupations, and married. About one
      quarter of the total live births were cesarean deliveries.

PMID- 29211490
TI  - Contraception among active component service women, U.S. Armed Forces, 2012-2016.
AB  - This report summarizes the annual prevalence of permanent sterilization, as well
      as use of long- and short-acting reversible contraceptives (LARCs and SARCs,
      respectively), contraceptive counseling services, and use of emergency
      contraception from 2012 through 2016 among active component U.S. service women.
      Overall, 262,907 (76.2%) women of childbearing potential used either a LARC or a
      SARC at some time during the surveillance period. From 2012 through 2016,
      permanent sterilization decreased from 4.2% to 3.6%; LARC use increased from
      17.2% to 21.7%; SARC use decreased from 38.5% to 30.4%; and emergency
      contraception use increased from 0.4% to 1.9%. Annual prevalence of contraceptive
      counseling only was relatively stable around 4.0%. This report estimates the
      length of continuation of LARCs, demonstrating that 86.1% continued their
      intrauterine device at 12 months, 78.5% at 24 months, and 73.4% at 36 months.
      These data demonstrate that the vast majority of service women have utilized at
      least one form of contraception, and that women are selecting LARCs in greater
      numbers with each passing year. The prevalence of contraceptive utilization among
      deployed service women is also reported.

PMID- 29211491
TI  - Complications and care related to pregnancy, labor, and delivery among active
      component service women, U.S. Armed Forces, 2012-2016.
AB  - Diagnoses of "complications of pregnancy, childbirth, and the puerperium" include
      both morbid complications and indications for routine care of pregnant women.
      During 2012-2016, a total of 55,601 U.S. service members with live births
      (n=63,879) had 657,060 medical encounters with primary diagnoses of "pregnancy
      complications." The most frequent diagnoses were "other" specified conditions
      complicating pregnancy, childbirth, or the puerperium. Numbers of medical
      encounters with a primary (first-listed) diagnosis of any pregnancy-related
      complication or indication for care decreased marginally each year between 2012
      (n=178,703) and 2016 (n=146,282). The percentage of live births affected by pre
      eclampsia and gestational diabetes remained relatively stable during the
      surveillance period. For all age groups, percentages of live births affected by
      preterm labor decreased, but live births affected by obesity complications
      increased. The percentage of live births affected by gestational diabetes was
      more than twice as high for obese women, compared with non-obese women (12.4% vs.
      5.5%). Findings suggest some opportunities to prevent sequelae for the mother and
      child and to mitigate longer-term impacts on force readiness.

PMID- 29211492
TI  - Incidence and burden of gynecologic disorders, active component service women,
      U.S. Armed Forces, 2012-2016.
AB  - This report describes the incidence, burden, and co-occurrence of four common
      gynecologic disorders among active component service women during 2012-2016.
      Overall incidence rates were highest for menorrhagia (100.9 per 10,000 person
      years [p-yrs]), followed by uterine fibroids (63.2 per 10,000 p-yrs),
      endometriosis (30.8 per 10,000 p-yrs), and polycystic ovary syndrome (PCOS, 25.3
      per 10,000 p-yrs). Annual incidence rates and medical encounters for menorrhagia
      decreased by roughly 50% from 2012 through 2015, and then increased slightly in
      2016. Annual incidence rates of PCOS decreased modestly between 2012 and 2016,
      whereas rates for endometriosis and uterine fibroids remained relatively stable.
      Service women in the Army, older service women, and non-Hispanic black service
      women had overall higher rates of menorrhagia, uterine fibroids, and
      endometriosis. Incidence of PCOS was highest among women aged 25-29 years, non
      Hispanic black service women, and service women in the Air Force. Approximately
      one-quarter (25.6%) of women with incident endometriosis, one-third (33.6%) of
      women with incident uterine fibroids, and 7% of women with PCOS had a co
      occurring incident diagnosis for menorrhagia during the surveillance period.
      Additional research focused on the severity of these conditions would allow for a
      fuller examination of the impact of these disorders on the readiness of the force
      and on healthcare utilization.

PMID- 29211493
TI  - Department of Defense Birth and Infant Health Registry: select reproductive
      health outcomes, 2003-2014.
AB  - Established following a 1998 directive, the Department of Defense Birth and
      Infant Health Registry (Registry) team conducts surveillance of select
      reproductive health outcomes among military families. Data are compiled from the
      Military Health System Data Repository and Defense Manpower Data Center to define
      the Registry cohort and outcomes of interest. Outcomes are defined using ICD
      9/ICD-10 and Current Procedural Terminology codes, and include: pregnancy
      outcomes (e.g., live births, losses), birth defects, preterm births, and
      male:female infant sex ratio. This report includes data from 2003-2014 on
      1,304,406 infants among military families and 258,332 pregnancies among active
      duty women. Rates of common adverse infant and pregnancy outcomes were comparable
      to or lower than those in the general US population. These observations, along
      with prior Registry analyses, provide reassurance that military service is not
      independently associated with increased risks for select adverse reproductive
      health outcomes. The Registry's diverse research portfolio demonstrates its
      unique capabilities to answer a wide range of questions related to reproductive
      health. These data provide the military community with information to identify
      successes and areas for improvement in prevention and care.

PMID- 29211495
TI  - Precision Medicine for Extracorporeal CO2 Removal for Acute Respiratory Distress
      Syndrome: CO2 Physiological Considerations.

PMID- 29211494
TI  - Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic
      Obstructive Pulmonary Disease.
AB  - RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease
      (COPD) over a period that spans decades. Despite the importance of COPD, much
      remains to be learned about susceptibility and pathogenesis, especially during
      early, prediagnostic stages of disease. Airway basal progenitor cells are crucial
      for lung health and resilience because of their ability to repair injured
      airways. In COPD, the normal airway epithelium is replaced with increased basal
      and secretory (mucous) cells and decreased ciliated cells, suggesting that
      progenitors are impaired. OBJECTIVES: To examine airway basal progenitor cells
      and lung function in smokers with and without COPD. METHODS: Bronchial biopsies
      taken from smokers at risk for COPD and lung cancer were used to acquire airway
      basal progenitor cells. They were evaluated for count, self-renewal, and
      multipotentiality (ability to differentiate to basal, mucous, and ciliated
      cells), and progenitor count was examined for its relationship with lung
      function. MEASUREMENTS AND MAIN RESULTS: Basal progenitor count, self-renewal,
      and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors
      produced an epithelium with increased basal and mucous cells and decreased
      ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated
      with lung function and identified a subset of subjects without COPD with lung
      function that was midway between non-COPD with high progenitor counts and those
      with COPD. CONCLUSIONS: Basal progenitor dysfunction relates to the histologic
      and physiologic manifestations of COPD and identifies a subset that may represent
      an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is
      involved in COPD pathogenesis.

PMID- 29211496
TI  - Reply to Morales-Quinteros et al.: Precision Medicine for Extracorporeal CO2
      Removal for Acute Respiratory Distress Syndrome: CO2 Physiological
      Considerations.

PMID- 29211498
TI  - Availability of Data Supporting Tables and Figures in Articles.

PMID- 29211497
TI  - The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of
      Experimental Pulmonary Fibrosis.
AB  - Pulmonary fibrosis is thought to result from dysregulated wound repair after
      repetitive lung injury. Many cellular responses to injury involve rearrangements
      of the actin cytoskeleton mediated by the two isoforms of the Rho-associated
      coiled-coil-forming protein kinase (ROCK), ROCK1 and ROCK2. In addition,
      profibrotic mediators such as transforming growth factor-beta, thrombin, and
      lysophosphatidic acid act through receptors that activate ROCK. Inhibition of
      ROCK activation may be a potent therapeutic strategy for human pulmonary
      fibrosis. Pharmacological inhibition of ROCK using nonselective ROCK inhibitors
      has been shown to prevent fibrosis in animal models; however, the specific roles
      of each ROCK isoform are poorly understood. Furthermore, the pleiotropic effects
      of this kinase have raised concerns about on-target adverse effects of ROCK
      inhibition such as hypotension. Selective inhibition of one isoform might be a
      better-tolerated strategy. In the present study, we used a genetic approach to
      determine the roles of ROCK1 and ROCK2 in a mouse model of bleomycin-induced
      pulmonary fibrosis. Using ROCK1- or ROCK2-haploinsufficient mice, we found that
      reduced expression of either ROCK1 or ROCK2 was sufficient to protect them from
      bleomycin-induced pulmonary fibrosis. In addition, we found that both isoforms
      contribute to the profibrotic responses of epithelial cells, endothelial cells,
      and fibroblasts. Interestingly, ROCK1- and ROCK2-haploinsufficient mice exhibited
      similar protection from bleomycin-induced vascular leak, myofibroblast
      differentiation, and fibrosis; however, ROCK1-haploinsufficient mice demonstrated
      greater attenuation of epithelial cell apoptosis. These findings suggest that
      selective inhibition of either ROCK isoform has the potential to be an effective
      therapeutic strategy for pulmonary fibrosis.

PMID- 29211499
TI  - Prevalence of alcohol impairment and odds of a driver injury or fatality in on
      road farm equipment crashes.
AB  - OBJECTIVE: The objective of this article was to estimate the prevalence of
      alcohol impairment in crashes involving farm equipment on public roadways and the
      effect of alcohol impairment on the odds of crash injury or fatality. METHODS: On
      road farm equipment crashes were collected from 4 Great Plains state departments
      of transportation during 2005-2010. Alcohol impairment was defined as an involved
      driver having blood alcohol content of >=0.08 g/100 ml or a finding of alcohol
      impairment as a driver contributing circumstance recorded on the police crash
      report. Injury or fatality was categorized as (a) no injury (no and possible
      injury combined), (b) injury (nonincapacitating or incapacitating injury), and
      (c) fatality. Hierarchical multivariable logistic regression modeling, clustered
      on crash, was used to estimate the odds of an injury/fatality in crashes
      involving an alcohol-impaired driver. RESULTS: During the 5 years under study,
      3.1% (61 of 1971) of on-road farm equipment crashes involved an alcohol-impaired
      driver. One in 20 (5.6%) injury crashes and 1 in 6 (17.8%) fatality crashes
      involved an alcohol-impaired driver. The non-farm equipment driver was
      significantly more likely to be alcohol impaired than the farm equipment driver
      (2.4% versus 1.1% respectively, P = .0012). After controlling for covariates,
      crashes involving an alcohol-impaired driver had 4.10 (95% confidence interval
      [CI], 2.30-7.28) times the odds of an injury or fatality. In addition, the non
      farm vehicle driver was at 2.28 (95% CI, 1.92-2.71) times higher odds of an
      injury or fatality than the farm vehicle driver. No differences in rurality of
      the crash site were found in the multivariable model. CONCLUSION: On-road farm
      equipment crashes involving alcohol result in greater odds of an injury or
      fatality. The risk of injury or fatality is higher among the non-farm equipment
      vehicle drivers who are also more likely to be alcohol impaired. Further studies
      are needed to measure the impact of alcohol impairment in on-road farm equipment
      crashes.

PMID- 29211500
TI  - Correlates of Tinder Use and Risky Sexual Behaviors in Young Adults.
AB  - Tinder is a frequently used geosocial networking application that allows users to
      meet sexual partners in their geographical vicinity. Research examining Tinder
      use and its association with behavioral outcomes is scarce. The objectives of
      this study were to explore the correlates of Tinder use and risky sexual
      behaviors in young adults. Participants aged 18-26 were invited to complete an
      anonymous online questionnaire between January and May 2016. Measures included
      sociodemographic characteristics, Tinder use, health related behaviors, risky
      sexual behaviors, and sexual attitudes. Associations among these variables were
      estimated using multivariate logistic regressions. The final sample consisted of
      415 participants (n = 166 Tinder users; n = 249 nonusers). Greater likelihood of
      using Tinder was associated with a higher level of education (OR = 2.18) and
      greater reported need for sex (OR = 1.64), while decreased likelihood of using
      Tinder was associated with a higher level of academic achievement (OR = 0.63),
      lower sexual permissiveness (OR = 0.58), living with parents or relatives (OR =
      0.38), and being in a serious relationship (OR = 0.24). Higher odds of reporting
      nonconsensual sex (OR = 3.22) and having five or more previous sexual partners
      (OR = 2.81) were found in Tinder users. Tinder use was not significantly
      associated with condom use. This study describes significant correlates of using
      Tinder and highlights a relationship between Tinder use with nonconsensual sex
      and number of previous sexual partners. These findings have salience for aiding
      public health interventions to effectively design interventions targeted at
      reducing risky sexual behaviors online.

PMID- 29211501
TI  - Viral subversion of APOBEC3s: Lessons for anti-tumor immunity and tumor
      immunotherapy.
AB  - APOBEC3s (A3) are endogenous DNA-editing enzymes that are expressed in immune
      cells including T lymphocytes. A3s target and mutate the genomes of retroviruses
      that infect immune tissues such as the human immunodeficiency virus (HIV).
      Therefore, A3s were classically defined as host anti-viral innate immune factors.
      In contrast, we and others showed that A3s can also benefit the virus by
      mediating escape from adaptive immune recognition and drugs. Crucially, whether
      A3-mediated mutations help or hinder HIV, is not up to chance. Rather, the virus
      has evolved multiple mechanisms to actively and maximally subvert A3 activity.
      More recently, extensive A3 mutational footprints in tumor genomes have been
      observed in many different cancers. This suggests a role for A3s in cancer
      initiation and progression. On the other hand, multiple anti-tumor activities of
      A3s have also come to light, including impact on immune checkpoint molecules and
      possible generation of tumor neo-antigens. Here, we review the studies that
      reshaped the view of A3s from anti-viral innate immune agents to host factors
      exploited by HIV to escape from immune recognition. Viruses and tumors share many
      attributes, including rapid evolution and adeptness at exploiting mutations.
      Given this parallel, we then discuss the pro- and anti-tumor roles of A3s, and
      suggest that lessons learned from studying A3s in the context of anti-viral
      immunity can be applied to tumor immunotherapy.

PMID- 29211502
TI  - Physical activity: perceptions of people with severe traumatic brain injury
      living in the community.
AB  - PRIMARY OBJECTIVE: Increasing physical activity (PA) among people with severe
      traumatic brain injury (TBI) represents an important long-term rehabilitation
      goal. To design effective interventions to promote PA, the factors associated
      with PA engagement post-TBI need to be understood. RESEARCH DESIGN: A qualitative
      study design was employed to investigate the factors influencing PA engagement in
      people with severe TBI living in the community. METHODS AND PROCEDURES: Face-to
      face interviews were conducted with eight people with severe TBI three to five
      years post-injury. A constant comparative method of data collection and analysis
      was adopted. MAIN OUTCOMES AND RESULTS: Interviews were analysed using thematic
      analysis. Three themes were identified: continuance of self and PA (perception of
      self, stage of life, and PA normality), beliefs about PA (knowledge of PA and
      associated benefits), and purpose of PA engagement (reasons for being physically
      active). Lifelong PA habits and current life priorities impacted on PA engagement
      post-TBI and influenced whether TBI-associated impairments were considered as a
      barrier to PA. CONCLUSION: Among this group of people, PA engagement post-TBI was
      influenced by perceptions of lifelong PA habits and current life priorities.
      Interventions to increase PA need to address these perceptions and adapt PA to
      account for life priorities within the context of TBI-associated impairments.

PMID- 29211503
TI  - National Health Care Spending In 2016: Spending And Enrollment Growth Slow After
      Initial Coverage Expansions.
AB  - Total nominal US health care spending increased 4.3 percent and reached $3.3
      trillion in 2016. Per capita spending on health care increased by $354, reaching
      $10,348. The share of gross domestic product devoted to health care spending was
      17.9 percent in 2016, up from 17.7 percent in 2015. Health spending growth
      decelerated in 2016 following faster growth in 2014 and 2015 associated with
      coverage expansions under the Affordable Care Act (ACA) and strong retail
      prescription drug spending growth. In 2016 the slowdown was broadly based, as
      spending for the largest categories by payer and by service decelerated.
      Enrollment trends drove the slowdown in Medicaid and private health insurance
      spending growth in 2016, while slower per enrollee spending growth influenced
      Medicare spending. Furthermore, spending for retail prescription drugs slowed,
      partly as a result of lower spending for drugs used to treat hepatitis C, while
      slower use and intensity of services drove the slowdown in hospital care and
      physician and clinical services.

PMID- 29211504
TI  - Usefulness of the Mobile Virtual Reality Self-Training for Overcoming a Fear of
      Heights.
AB  - A mobile virtual reality system, equipped with built-in variables such as heart
      rate (HR), gaze-down data, and subjective fear rating, can allow individuals with
      a fear of heights to overcome it by self-training. This study aimed to verify the
      efficacy and safety of the training program. Forty-eight volunteers completed the
      four-session self-training program over 2 weeks. They were allocated into either
      low- or high-fear group by the Acrophobia Questionnaire (AQ)-anxiety scores, and
      then the changes of the built-in variables and AQ-anxiety scores were analyzed
      between the groups. The safety was assessed using the Simulator Sickness
      Questionnaire (SSQ). The AQ-anxiety scores were significantly decreased after
      self-training in both groups, and the degree of decrease was significantly
      greater in the high-fear group than in the low-fear group. Gaze-down percentage
      and subjective fear rating showed a significant group difference, but HR did not.
      The SSQ scores were within the acceptable level. These results suggest that the
      training effect was greater in the high-fear group than in the low-fear group.
      This mobile program may be safely applicable to self-training for individuals
      with high scores on the fear of heights by repeated exposure to virtual
      environments with the embedded feedback system.

PMID- 29211505
TI  - The Effect of Dietary Nitrate on Nocturnal Sleep-Disordered Breathing and
      Arterial Oxygen Desaturation at High Altitude.
AB  - Patrician, Alexander, Harald Engan, David Lundsten, Ludger Grote, Helena Vigetun
      Haughey, and Erika Schagatay. The effect of dietary nitrate on nocturnal sleep
      disordered breathing and arterial oxygen desaturation at high altitude. High Alt
      Med Biol 19:21-27, 2018.-Sleep-disordered breathing and fluctuations in arterial
      oxygen saturation (SaO2) are common during sleep among lowlanders ascending to
      high altitude. Dietary nitrate (NO3-) supplementation has been shown to lower the
      O2 consumption in various conditions. Our objective was to investigate whether
      dietary NO3- could reduce sleep-disordered breathing and SaO2 desaturation during
      sleep at altitude. Cardiorespiratory responses during sleep were measured in 10
      healthy lowlanders at 330 m and then again in the Himalayas at 3700-4900 m. Each
      subject received two 70 mL shots of either beetroot juice (BR; ~5.0 mmol NO3- per
      shot) or placebo (PL: ~0.003 mmol NO3- per shot) in a single-blinded, weighted
      order over two consecutive nights at altitude. At 2.5-4.5 hours into sleep at
      altitude, BR increased the SaO2 desaturation drop (4.2 [0.1]% with PL vs. 5.3
      [0.4]% with BR; p = 0.024) and decreased the SaO2 desaturation duration (14.1
      [0.9] seconds with PL to 11.1 [0.9] seconds with BR; p = 0.0.041). There was a
      reduction in breaths with flow limitation (p = 0.025), but no changes in Apnea
      Hypopnea Index (AHI), mean and minimum SaO2. The study suggests BR
      supplementation does not improve AHI or oxygenation, but may increase
      fluctuations in arterial O2 saturation during sleep at altitude in native
      lowlanders.

PMID- 29211506
TI  - Validity of low-resolution eye-tracking to assess eye movements during a rapid
      number naming task: performance of the eyetribe eye tracker.
AB  - OBJECTIVE: To evaluate the performance of the EyeTribe compared to the EyeLink
      for eye movement recordings during a rapid number naming test in healthy control
      participants. BACKGROUND: With the increasing accessibility of portable,
      economical, video-based eye trackers such as the EyeTribe, there is growing
      interest in these devices for eye movement recordings, particularly in the domain
      of sports-related concussion. However, prior to implementation there is a primary
      need to establish the validity of these devices. One current limitation of
      portable eye trackers is their sampling rate (30-60 samples per second, or Hz),
      which is typically well below the benchmarks achieved by their research-grade
      counterparts (e.g., the EyeLink, which samples at 500-2000 Hz). METHODS: We
      compared video-oculographic measurements made using the EyeTribe with those of
      the EyeLink during a digitized rapid number naming task (the King-Devick test) in
      a convenience sample of 30 controls. RESULTS: EyeTribe had loss of signal during
      recording, and failed to reproduce the typical shape of saccadic main sequence
      relationships. In addition, EyeTribe data yielded significantly fewer detectable
      saccades and displayed greater variance of inter-saccadic intervals than the
      EyeLink system. CONCLUSION: Caution is advised prior to implementation of low
      resolution eye trackers for objective saccade assessment and sideline concussion
      screening.

PMID- 29211507
TI  - Association of shiftwork and leukocytes among national health and nutrition
      examination survey respondents.
AB  - Shift workers may experience disrupted sleep-wake or circadian cycles which, in
      turn, may lead to major health problems such as hypertension, obesity, and
      diabetes. Research indicates that shift workers have increased levels of
      leukocytes. Data from the National Health and Nutrition Examination Survey (2005
      2010) examined the relationship between self-reported current shiftwork and
      leukocytes with adjustment for important confounders. Using linear regression, we
      found no association between shiftwork and leukocyte counts. Those not working
      had elevated levels compared to day workers but values in both groups were still
      within normal ranges. Additional research is needed to fully understand how
      shiftwork influences changes in leukocyte counts.

PMID- 29211508
TI  - Exploring Stereotypical Perceptions of Female Players in Digital Gaming Contexts.
AB  - Gender stereotypes are still reported to exist in digital gaming contexts,
      despite the fact that participation of females is relatively equal to that of
      males. The current research explored a number of factors and their impact upon
      stereotypical perceptions and attitudes toward female players. This included
      avatar gender, gender identity by gaming context, as well as more general gender
      role beliefs. We undertook two studies, each utilizing an online questionnaire
      targeted toward online players. Study 1 recruited online gamers (N = 489) and
      compared competence perceptions of players, which varied by player gender (male,
      female) and avatar gender (male, female), whereby four conditions were
      established. Overall, player competence was perceived to be highest when male
      avatars were used, specifically when female players were depicted in this way.
      Study 2 explored the relationships between male social identity and gender-role
      beliefs, with sexist attitudes in gaming, and whether this varied by gaming
      context (massively multiplayer online [MMO] vs. first-person shooter [FPS]). Male
      online gamers (N = 193) were recruited, of which 112 were MMO players, and 81
      were FPS players. It was found that identifying as male social identity was not
      related to sexist attitudes in either gaming context. However, more general
      gender-role beliefs were related to sexist attitudes. The findings indicate that
      although certain stereotypes exist (e.g., competence perceptions), these are not
      necessarily harvested by players' identities within communities, but may derive
      through more operational functions such as avatar gender.

PMID- 29211509
TI  - Pharmacist-based antihypertensive medication review and assignment of morning
      versus evening dosing of once-daily antihypertensive medications: A pilot study
      to assess feasibility and efficacy in chronic kidney disease patients.
AB  - Evening dosing of antihypertensive medications lowers nighttime blood pressure,
      and in one large randomized trial, it reduced the risk for cardiovascular
      outcomes. However, the feasibility of nighttime dosing in routine clinical
      practice is unknown. The purpose of this pilot study was to evaluate the effect
      of a brief pharmacist intervention to assign patients to take antihypertensive
      medications at specific times of the day. In this pilot, randomized controlled
      trial, 79 patients with moderate to severe chronic kidney disease (CKD) taking
      one or more antihypertensive medications once daily were randomized to take one
      once-daily antihypertensive either in the morning or in the evening. A total of
      79 patients were randomized (39 to morning dosing, 40 to evening dosing). Average
      (SD) age was 56.5 (14) years, 68% were male, and average (SD) estimated
      glomerular filtration rate (eGFR) was 36.6 (8.9) mL/min/1.73m2. Adherence,
      defined as taking the once-daily medication at the time indicated six or seven
      times in the last 7 days and not taking it at any other time during the day, was
      91% in the morning arm and 95% in the evening arm (p = 0.57). This pilot
      demonstrates the feasibility and efficacy of a pharmacist-physician collaborative
      to assign once-daily antihypertensive medications to either morning or evening
      dosing.

PMID- 29211510
TI  - Forced desynchronization model for a diurnal primate.
AB  - The circadian system is organized in a hierarchy of multiple oscillators, with
      the suprachiasmatic nucleus (SCN) as the master oscillator in mammals. The SCN is
      formed by a group of coupled cell oscillators. Knowledge of this coupling
      mechanism is essential to understanding entrainment and the expression of
      circadian rhythms. Some authors suggest that light-dark (LD) cycles with periods
      near the limit of entrainment may be good models for promoting internal
      desynchronization, providing knowledge about the coupling mechanism. As such, we
      evaluated the circadian activity rhythm (CAR) pattern of marmosets in LD cycles
      at lower limits of entrainment in order to study induced internal dissociation.
      To that end, two experiments were conducted: (1) 6 adult females were under
      symmetrical LD cycles T21, T22 and T21.5 for 60, 35 and 48 days, respectively;
      and (2) 4 male and 4 female adults were under T21 for 24 days followed by 18 days
      of LL, back to T21 for 24 days, followed by 14 days of LL. The CAR of each animal
      was continuously recorded. In experiment 1, vocalizations were also recorded.
      Under Ts shorter than 24 days, a dissociation pattern was observed for CAR and
      vocalizations. Two simultaneous circadian components emerged, one with the same
      period as the LD cycle, called the light-entrained component, and the other in
      free-running, denominated the non-light-entrained component. Both components were
      displayed in the CAR for all the animals in T21, five animals (83.3%) in T21.5
      and two animals (33.3%) in T22. Our results are in accordance with the
      multioscillatory nature of the circadian system. Dissociation is partial
      synchronization to the LD cycle, with at least one group of oscillators
      synchronized by relative coordination and masking, while another group of
      oscillators free runs, but is also masked by the LD cycle. Since only T21
      promoted the emergence of both circadian components in the circadian rhythms of
      all marmosets, it was considered the promoter period of circadian rhythm
      dissociation in this species, and is proposed as a good animal model for forced
      desynchronization in non-human diurnal primates.

PMID- 29211511
TI  - Mitochondrial tRNAAla C5601T mutation may modulate the clinical expression of
      tRNAMet A4435G mutation in a Han Chinese family with hypertension.
AB  - Mutations in mitochondrial DNA, especially in mitochondrial tRNA (mt-tRNA) genes,
      are the important causes for maternally inherited hypertension. In this study, we
      reported the clinical, genetic, and molecular characterization of a Han Chinese
      family with hypertension. Most strikingly, this family exhibited a high
      penetrance and expressivity of hypertension. Sequence analysis of the complete mt
      tRNA genes showed the presence of tRNAMet A4435G and tRNAAla C5601T mutations.
      The A4435G had already been reported as a pathogenic mutation associated with
      hypertension; in addition, the C5601T mutation, which was located at the highly
      conserved nucleotide of T arm of tRNAAla, created a novel Watson-Crick base
      pairing and may result in failure of tRNA metabolism. Moreover, bioinformatics
      analysis indicated that the C5601T mutation altered the secondary structure of
      tRNAAla. Thus, the mitochondrial dysfunction, caused by the A4435G mutation, may
      be worsened by the C5601T mutation. Taken together, our data indicated that the
      co-occurrence of the A4435G and C5601T mutations may account for the high
      penetrance and expressivity of hypertension in this family. Therefore, our study
      provided novel insight into the pathophysiology of maternally inherited
      hypertension.

PMID- 29211512
TI  - Durability of Second Antiretroviral Regimens in the Italian Cohort Naive
      Antiretrovirals Foundation Study and Factors Associated with Discontinuation.
AB  - The study was designed to investigate the median duration of second
      antiretroviral regimens and factors associated with early discontinuation in HIV
      patients who switched with an undetectable viral load. We conducted a
      retrospective analysis of the Italian Cohort Naive Antiretrovirals Foundation
      Study (ICONA), which collects data throughout the country. Patients who started
      first antiretroviral therapy (ART) after January 1, 2008 in any center involved
      in this cohort and then switched to a second regimen were included in the study.
      Second ART failure was described as two HIV-RNA >200 copies/mL or the
      discontinuation of any drug. Statistical analysis was performed utilizing Kaplan
      Meier curves and Cox regression model. The study population included 835 patients
      and the median duration of first ART regimens was 16 months with HIV-RNA
      undetectable for 13 months. The main causes of switch to second ART regimens were
      toxicity (42.5%) and simplification (37.5%). The switch mostly involved the third
      drug (63.5%) and almost one third of the population received a single-tablet
      regimen (STR) as second treatment (30.6%). The median duration of second ART
      regimens was 9.2 months and the probabilities of treatment discontinuation at 12,
      24, and 36 months were 21%, 35%, and 48.2%, respectively. STR formulations had a
      protective effect against second ART discontinuation. Almost half of our
      population needed a third regimen within 3 years, but STR could improve second
      ART durability.

PMID- 29211514
TI  - HIV Care Providers' Intentions to Prescribe and Actual Prescription of Pre
      Exposure Prophylaxis to At-Risk Adolescents and Adults.
AB  - Pre-exposure prophylaxis (PrEP) is indicated for use in US adults, and little is
      known about clinician intentions to prescribe and actual prescription of PrEP to
      adolescents younger than 18. Fifty-six clinicians who care for HIV-infected and
      at-risk youth completed an anonymous online survey in 2014. Primary outcomes were
      (1) intentions to prescribe PrEP to adolescents and adults in four risk
      categories [men who have sex with men (MSM), transgender women, heterosexuals
      with multiple partners of unknown HIV status, heterosexuals with HIV-infected
      partners]; and (2) actual prescription of PrEP to adolescents and adults in these
      risk groups. Independent variables included clinician characteristics, experience
      prescribing nonoccupational postexposure prophylaxis, familiarity with and
      knowledge of PrEP and PrEP guidance, attitudes toward PrEP, and facilitating
      factors for prescribing PrEP and incorporation of PrEP guidance into practice.
      Variables associated with intention to prescribe ("very likely to prescribe" vs.
      other responses) and actual prescription of PrEP stratified by age and risk
      category were identified in logistic regression models. Mean age was 45.9 years
      (standard deviation 10.7); 64% were physicians. More clinicians reported high
      intention to prescribe PrEP to adult versus adolescent MSM (p = 0.02) and
      transgender women (p = 0.001). Variables associated with intention to prescribe
      and prescription of PrEP differed by age and risk category. In adolescents, those
      variables included positive beliefs, higher number of facilitating factors, and
      fewer barriers to PrEP prescription. Designing strategies based on these findings
      that address both facilitating factors and barriers to PrEP prescription may
      improve PrEP uptake by at-risk youth.

PMID- 29211513
TI  - Facilitators and Barriers to Pre-Exposure Prophylaxis Willingness Among Young Men
      Who Have Sex with Men Who Use Geosocial Networking Applications in California.
AB  - While correlates of pre-exposure prophylaxis (PrEP) uptake have been explored
      among older men who have sex with men (MSM), less is known about the facilitators
      and barriers that encourage uptake among younger MSM (YMSM). This study explores
      the association between willingness to take PrEP and demographic characteristics,
      sexual risk, and substance use, and attitudinal factors among YMSM in California
      who use geosocial networking applications (GSN apps). Based on survey data from
      YMSM recruited through GSN apps (n = 687), PrEP willingness was positively
      associated with Hispanic ethnicity [adjusted odds ratio (aOR): 1.73; confidence
      interval (CI): 1.01-2.98; p = 0.046], concerns about drug effects (aOR: 0.46; CI:
      0.33-0.65; p < 0.001), medical mistrust (aOR: 0.71; CI: 0.53-0.96; p < 0.001),
      and concerns about adherence (aOR: 0.65; CI: 0.49-0.89; p = 0.005). PrEP
      willingness was positively associated with medium (aOR: 1.87; CI: 1.14-3.07; p =
      0.014) and high concern (aOR: 1.84; CI: 1.13-3.01; p < 0.001) about contracting
      HIV and perceived benefits of taking PrEP (aOR: 2.59; CI: 1.78-3.78; p < 0.001).
      In addition to emphasizing the benefits of using PrEP, campaigns that address
      concerns regarding adherence and side effects may increase interest in and demand
      for PrEP among YMSM. More opportunities are needed to educate YMSM about PrEP,
      including addressing their concerns about this new prevention strategy. Providers
      should speak openly and honestly to YMSM considering PrEP about what to do if
      side effects occur and how to handle missed doses. Outreach using GSN apps for
      PrEP education and screening may be an effective way to reach YMSM.

PMID- 29211515
TI  - Factors Associated with Use of Short-Term Pre-Exposure Prophylaxis for HIV Among
      Female Partners of Migrant Miners in Mozambique.
AB  - Effective interventions tailored to specific types of behaviors and contexts are
      needed for women at risk for HIV acquisition. Oral pre-exposure prophylaxis
      (PrEP) is an efficacious HIV prevention intervention that uses antiretroviral
      drugs to reduce the risk of acquiring HIV infection. In Mozambique, HIV remains a
      major public health concern, with a national prevalence of 13%. Studies have
      demonstrated that the migration of male miners between southern provinces of
      Mozambique and South Africa is contributing to the HIV epidemic in Mozambique.
      This increased risk is associated with the engagement of male miners, while
      separated from their partners, in sexual relationships with other women,
      including transactional sex workers, in a hyperendemic setting in South Africa.
      We conducted 25 in-depth interviews with a subset of female partners in a stable
      relationship with migrant miners participating in a prospective cohort study to
      assess the feasibility, acceptability, and adherence to daily oral short-term
      PrEP. Drug levels were available for the participants, as reported in an earlier
      study. Interviews were recorded, transcribed, and submitted for qualitative
      thematic analysis. The major themes identified were the benefits of taking PrEP,
      the ease of taking daily PrEP, the reluctance to disclose PrEP use to partners,
      the lack of changes in sexual behavior, and prevailing gender dynamics and how
      they impact women's ability to access PrEP and other HIV prevention
      interventions.

PMID- 29211516
TI  - Racial Discrimination and Low Household Education Predict Higher Body Mass Index
      in African American Youth.
AB  - OBJECTIVE: The purpose of this study was to examine the relationships between
      environmental factors, including household education, community violence
      exposure, racial discrimination, and cultural identity, and BMI in African
      American adolescents. METHODS: A community-based sample of 198 African American
      youth (120 girls, 78 boys; ages 11-19 years) from Washtenaw County, Michigan,
      were included in this analysis. Violence exposure was assessed by using the
      Survey of Children's Exposure to Community Violence; racial discrimination by
      using the Adolescent Discrimination Distress Index; cultural identity by using
      the Acculturation, Habits, and Interests Multicultural Scale for Adolescents; and
      household education by using a seven-category variable. Measured height and body
      weight were used to calculate BMI. RESULTS: Racial discrimination was positively
      associated with BMI, whereas household education was inversely associated with
      BMI in African American adolescents (discrimination: beta = 0.11 +/- 0.04, p =
      0.01; education: beta = -1.13 +/- 0.47, p = 0.02). These relationships were
      significant when accounting for the confounding effects of stress, activity,
      diet, and pubertal development. Significant gender interactions were observed
      with racial discrimination and low household education associated with BMI in
      girls only (discrimination: beta = 0.16 +/- 0.05, p = 0.003; education: beta = 
      1.12 +/- 0.55, p = 0.045). There were no significant relationships between
      culture, community violence exposure, and BMI (all p's > 0.05). CONCLUSION:
      Environmental factors, including racial discrimination and low household
      education, predicted higher BMI in African American adolescents, particularly
      among girls. Longitudinal studies are needed to better understand the mechanisms
      by which these environmental factors increase obesity risk in African American
      youth.

PMID- 29211517
TI  - HPV Vaccination: Increase Uptake Now to Reduce Cancer.

PMID- 29211518
TI  - AJPH Global News.

PMID- 29211519
TI  - Reflections on the 70th Anniversary of the Nuremberg Doctors' Trial.

PMID- 29211520
TI  - Preparing and Rebuilding After Natural Disasters: A New Public Health Normal!

PMID- 29211521
TI  - Jeremy Struck a Chord: A Public Health Approach to Professional Musicians.

PMID- 29211522
TI  - Academic Literacy: Reaching Our Own.

PMID- 29211523
TI  - Conflict Settings: The Importance of Timely Access to Health Care.

PMID- 29211524
TI  - Three Stages of Health Encounters Over 8000 Human Generations and How They Inform
      Future Public Health.

PMID- 29211525
TI  - Marking the 70th Anniversary of the Doctors' Trial at Nuremberg.

PMID- 29211529
TI  - Can Public Health Narrow the Health Gap Between the United States and Its Peer
      Nations? A Public Health of Consequence, January 2018.

PMID- 29211530
TI  - Managing Childhood Asthma as a Strategy to Break the Cycle of Poverty.

PMID- 29211531
TI  - Calabrese et al. Respond.

PMID- 29211532
TI  - After Harvey, Irma, and Maria, an Opportunity for Better Health-Rebuilding Our
      Communities as We Want Them.

PMID- 29211533
TI  - PrEP-ared Against HIV, but Not Sexually Transmitted Infections.

PMID- 29211534
TI  - Disasters Through the Lens of Disparities: Elevate Community Resilience as an
      Essential Public Health Service.

PMID- 29211535
TI  - A Humanitarian Crisis: Lessons Learned From Hurricane Irma.

PMID- 29211536
TI  - Sexual Assertiveness Skills and Decision-Making in Adolescent Girls: Moving to
      Replication, Scale, and Digital Health Impact.

PMID- 29211537
TI  - Getting to Average Life Expectancy: It Takes Commitment.

PMID- 29211538
TI  - Enhancing HIV/AIDS Surveillance in the Philippines to Ensure the Transgender
      Population's Visibility.

PMID- 29211539
TI  - Public Health's Aspirational Identity: Who Do We Want to Be?

PMID- 29211540
TI  - Advertising Restrictions on Cannabis Products for Nonmedical Use: Necessary but
      Not Sufficient?

PMID- 29211541
TI  - Maria in Puerto Rico: Natural Disaster in a Colonial Archipelago.

PMID- 29211542
TI  - Climate Change, Hurricanes, and Health.

PMID- 29211543
TI  - Access to Medical Care for Palestinians in Israel: Delays in a Difficult
      Historical Context.

PMID- 29211544
TI  - The Type of Feeding at Discharge of Very Preterm Infants: Neonatal Intensive Care
      Units Policies and Practices Make a Difference.
AB  - OBJECTIVE: To assess the influence of neonatal intensive care units (NICUs) on
      feeding practices at discharge of Portuguese very preterm infants. MATERIALS AND
      METHODS: We analyzed data from 580 very preterm infants (<32 gestational weeks)
      discharged home from NICUs of two Portuguese regions and enrolled during 2011
      2012 in Effective Perinatal Intensive Care in Europe population-based cohort.
      Maternal and infant characteristics were abstracted from medical records, and
      heads of NICUs provided the units characteristics. Feeding at discharge was
      classified as exclusive formula, exclusive breast milk or mixed, and differences
      among NICUs were obtained by comparison with pooled geometric mean odds of all
      NICUs, using multinomial logistic regression. Median odds ratios (MOR) were
      calculated to quantify variability among NICUs using multilevel logistic
      regression. RESULTS: At discharge, 25.2% very preterm infants were exclusively on
      breast milk, 34.1% exclusively on formula, and 40.7% had mixed feeding, with a
      wide variation among NICUs. Exclusive breast milk increased in NICUs that had
      higher numbers of admissions, provided parents eating facilities, and by having
      designated members to support mothers who were breastfeeding. The individual NICU
      odds of mixed versus exclusive formula feeding ranged from 0.36 to 2.07 and for
      exclusive breast milk versus exclusive formula ranged from 0.16 and 5.11.
      Adjusting for individual and unit characteristics, heterogeneity across NICUs
      remained evident, being the MOR 1.33 for mixed feeding and 1.35 for exclusive
      breast milk. CONCLUSIONS: NICUs influence feeding practices independently of
      individual characteristics, highlighting the importance of institution-based
      interventions to promote breast milk.

PMID- 29211545
TI  - Efficacy and safety of benralizumab for eosinophilic asthma: A systematic review
      and meta-analysis of randomized controlled trials.
AB  - CONTEXT: Benralizumab is a humanized monoclonal antibody that targets the alpha
      chain of the IL-5 receptor (IL-5Ralpha) and is currently being assessed in
      clinical trials for asthma control. OBJECTIVE: Our systematic review and meta
      analysis intends to evaluate the therapeutic efficacy and safety of benralizumab
      in patients with eosinophilic asthma. DATA SOURCES AND EXTRACTION: Literature
      searches of PubMed, Embase, and the Cochrane Library were performed to identify
      randomized controlled trials of benralizumab and clinic outcomes in asthmatics.
      RESULTS: In total, 7 articles with 2,321 subjects met our inclusion criteria.
      From this pooled analysis, we found that benralizumab significantly reduces
      exacerbations (RR: 0.63, 95% CI: 0.52-0.76, p < 0.00001; I2 = 52%, p = 0.06)
      compared to placebo in eosinophilic asthma. There was no statistical trend for
      improvement in forced expiratory volume in 1 second or asthma control indices
      such as Quality of Life Assessment (AQLQ) and Asthma Control Questionnaire score
      in benralizumab-treated patients. In addition, safety data indicated that
      benralizumab administration resulted no increasing incidence of adverse events
      and was well tolerated (RR: 1.00, 95% CI: 0.95-1.05, p = 0.96; I2 = 40%, p =
      0.13). CONCLUSION: These results demonstrate the efficacy and safety of
      benralizumab for asthma patients with severe or uncontrolled symptoms and
      elevated eosinophils and provide support for benralizumab as an ideal option to
      treat asthma in this patient population.

PMID- 29211546
TI  - Association of outdoor air pollution with the prevalence of asthma in children of
      Latin America and the Caribbean: A systematic review and meta-analysis.
AB  - OBJECTIVE: This study aimed to evaluate the association between asthma prevalence
      and outdoor air pollution in children in Latin America and the Caribbean. DATA
      SOURCES: We searched studies in global and regional databases: PubMed, Scopus,
      LILACS and SciELO. STUDY SELECTION: Articles following a cross-sectional design,
      studying children from 0 to 18 years old, and comparing the prevalence of asthma
      in two or more areas of LAC countries with different air pollution levels were
      included. The exclusion criteria comprised air pollution not related to human
      activities. RESULTS: Database searches retrieved 384 records, while 20 studies
      were retained for qualitative and 16 for quantitative analysis, representing 48
      442 children. We found a positive association, i.e. a higher prevalence of asthma
      in children living in a polluted environment, with pooled odds ratio (OR) of 1.34
      (95% CI: 1.17-1.54). Heterogeneity between studies was moderate (I2: 68.39%),
      while the risk of bias was intermediate or high in 14 studies. In all the
      subgroup and sensitivity analyses, the pooled ORs were significant and higher
      than those found in the general analysis Conclusions: Our results showed that
      living in a polluted environment is significantly associated with children having
      asthma in LAC. Limitations of this study include the low number of studies
      performed in LAC countries, differences in methodologies and the risk of bias in
      individual studies.

PMID- 29211547
TI  - Prenatal exposure to polychlorinated biphenyls and asthma, eczema/hay fever, and
      frequent ear infections.
AB  - OBJECTIVES: The effects of prenatal exposure to Polychlorinated biphenyls (PCBs)
      on the development of asthma, frequent ear infections, and eczema/hay fever are
      not well understood. We aim to investigate associations between prenatal PCB
      exposure and these health outcomes in the offspring of women who worked at the
      LaSalle Electrical Utilities Company (EUC). METHODS: A retrospective cohort with
      at least one live birth and known employment time at EUC was eligible for this
      analysis. Exposure was defined and categorized by the number of fiscal quarters
      worked during the PCB era (1952-1981). A total of 288 women with 800 live births
      were included. A Chi-Square test was used to compare maternal and child
      characteristics across exposure groups and repeated measures logistic regression,
      controlling for clustering among siblings, was used to assess the associations
      between prenatal PCB exposure and these outcomes. RESULTS: After adjustment for
      confounding and independent maternal predictors, 1-4 quarters of prenatal
      exposure to PCBs increased the odds for asthma (OR 3.24[1.30-8.09]), eczema/hay
      fever (OR 3.29[1.54-7.04]), and frequent ear infections (OR 2.24[1.19-4.22]) when
      compared with persons unexposed/exposed only to naphthalenes. The significance of
      the associations varied by exposure period and level of exposure, with the
      strongest associations in those employed exclusively after 1952 when PCBs were
      introduced. CONCLUSIONS: These results support previous findings of associations
      of prenatal exposure to PCBs with asthma, eczema/hay fever, and frequent ear
      infections. Additional prospective studies are needed to confirm these findings.
      Also required are more precise PCB exposures to separate them from other
      exposures in occupational settings.

PMID- 29211549
TI  - Blistering disorders.
AB  - Preview Blisters are a manifestation of many diseases, which range from the
      trivial to the life-threatening. Distinguishing between these conditions can be
      crucial to the patient's well- being. Dr Olson presents an overview of the common
      causes of blistering, with emphasis on immunobullous diseases, which demand early
      recognition and prompt treatment.

PMID- 29211548
TI  - Aqueous Drainage Device Erosion: A Review of Rates, Risks, Prevention, and
      Repair.
AB  - Aqueous drainage device tube erosions require prompt intervention to prevent
      endophthalmitis. As the use of drainage devices in glaucoma surgery continues to
      increase, recognizing and managing tube erosions is a pertinent issue. This
      review provides a comprehensive overview of tube erosions, including the rates of
      erosion with various types of patch grafts, the risk factors associated with
      erosion, and approaches to repair in order to counsel and treat our patients to
      prevent endophthalmitis.

PMID- 29211550
TI  - Dermatologic emergencies.
AB  - Preview Several dermatoses are potentially fatal, and the mortality rate for some
      is quite high; prompt recognition and treatment are essential. Dr Gannon's
      succinct discussions of pemphigus vulgaris, necrotizing fasciitis, toxic
      epidermal necrolysis, Stevens-Johnson syndrome, toxic shock syndrome, and
      urticaria and angioedema will leave physicians well prepared to quickly identify
      these diseases and provide appropriate treatment.

PMID- 29211551
TI  - Unstable angina.
AB  - Preview Because unstable angina is often a precursor of myocardial infarction or
      death, patients with chest pain that persists for more than 20 minutes and is
      refractory to sublingual nitroglycerin should be hospitalized in an intensive
      care unit and given appropriate pharmacologic therapy. If symptoms persist
      despite adequate management with drugs, coronary arteriography should be
      performed and consideration given to an invasive procedure, such as angioplasty
      or coronary artery bypass grafting, for high-risk conditions. If necessary, the
      invasive procedure should be delayed until the patient's condition has
      stabilized.

PMID- 29211553
TI  - Rattlesnake bites.
AB  - Preview Rattlesnake bites can have a wide spectrum of physical consequences, some
      of them devastating. Opinion regarding appropriate management of this medical
      emergency is controversial and changing. In this article, the authors offer
      practical, up-to-date guidelines to expedite treatment that may be lifesaving.

PMID- 29211552
TI  - Screening for colorectal cancer.
AB  - Preview Although the optimal method of screening for colorectal cancer remains
      controversial, data clearly indicate that many deaths from the disease are
      preventable. Dr Lush summarizes the current recommendations for screening and
      reviews results of a recent study that found decreased mortality with use of a
      particular method of fecal occult blood testing without sigmoidoscopy.

PMID- 29211554
TI  - Phobias.
AB  - Preview When phobias compromise a person's normal lifestyle or cause ongoing
      anxiety, they must be dealt with. Irrational, persistent fears may lead to
      isolation, depression, even substance abuse. What are the features of
      agoraphobia? Social phobia? Simple phobia? How common are these anxiety
      disorders? The authors answer these questions and discuss differential diagnosis
      and treatment options.

PMID- 29211555
TI  - The Dirty Secret of Health Reform.

PMID- 29211556
TI  - Annular skin eruptions.
AB  - Preview Skin eruptions often occur in annular patterns. Fungal infections are one
      of the most common causes of ring-shaped eruptions, but annular patterns form in
      many other skin conditions as well. Dr Bart describes, illustrates, and discusses
      the causes and treatments of 24 disorders that can result in rings on the skin.

PMID- 29211557
TI  - Acoustophoretic purification of platelets: Feasibility and impact on platelet
      activation and function.
AB  - Purity, limited platelet activation, and preservation of platelet function are
      important stakes of preparation of platelet concentrates (PC) for clinical use.
      In fact, contaminating red blood cells and leukocytes, as well as activated
      and/or poorly functional platelets in PC, represents a risk of poor efficiency
      and adverse side effects during platelet transfusion. Therefore, optimization of
      preparation and storage of PC is still an active field of research. Shear-induced
      platelet activation is an unwanted side effect of the hard-spin (up to 5000g)
      step of centrifugation-based methods currently used in blood banks to prepare PC
      from whole blood samples. Here, we evaluated the effectiveness of an acoustic
      based fractionation device for the isolation of human platelets from whole blood
      bags. The purity, activation status, and functionality of platelets isolated by
      acoustopheresis were compared with those of platelets isolated using a reference
      protocol known to produce limited platelet activation and consisting of two
      consecutive soft-spin centrifugations (120g and 1200g). Platelet concentration
      and purity were determined using an automated hematology analyzer. Platelet
      activation status and platelet reactivity to collagen and thrombin were assessed
      in flow cytometry by measurement of surface expression of P-selectin and
      activated integrin alphaIIbbeta3. The ability of isolated platelets to
      incorporate into a thrombus when transfused to NOD/SCID mice was investigated by
      intravital microscopy using the ferric chloride-induced thrombosis model. Blood
      fractionation by acoustophoresis led to the elimination of more than 80% of red
      blood cells and leukocytes from the platelet fraction, whose mean purity was of
      92.8 +/- 12.8%. The activation status and reactivity to collagen and thrombin of
      acoustophoresis-isolated platelets were similar to those of platelets isolated by
      soft-spin centrifugation. Finally, acoustophoresis-isolated platelets were
      tethered, adhered to the vessel wall, and incorporated into a growing thrombus
      following ferric chloride-induced vascular injury. Together, our results indicate
      that acoustophoresis is a suitable method for the isolation of human platelets
      with minimal platelet activation and preservation of platelet function.

PMID- 29211558
TI  - Obstructive sleep apnea.
AB  - Preview Repeated occlusion of the upper airway during sleep results in the
      obstructive sleep apnea syndrome. Affected individuals may experience excessive
      daytime sleepiness, intellectual impairment, and personality changes, and their
      risk of cerebrovascular accidents, ischemic heart disease, and severe respiratory
      failure is increased. The authors of this article examine methods of recognizing
      the disorder, indications for treatment, and various medical and surgical
      approaches to management.

PMID- 29211559
TI  - Acute and chronic diarrhea.
AB  - Preview Whether the cause of diarrhea is relatively common (eg, contaminated
      water) or more rare (eg, carcinoid syndrome), the result is disconcerting. Since
      the list of tests available to aid in diagnosis is almost endless, physicians
      need to follow a systematic plan to avoid enormous laboratory charges. Drs Talal
      and Murray offer a pragmatic approach to differential diagnosis that is suited to
      the primary care setting.

PMID- 29211560
TI  - Cardiovascular risk factors.
AB  - Preview New information emerges almost weekly about the relative importance of
      one factor or another in the development of coronary artery disease. Yet
      controversies continue over which factor deserves the most emphasis. Dr Elliott
      presents a broad and, at times, humorous look at research into cardiovascular
      risk factors and explains how the results can influence medical practice and
      public healthcare policy.

PMID- 29211561
TI  - Intensified insulin regimens.
AB  - Preview The value of intensified insulin regimens in slowing the progression of
      microvascular complications in patients with type I diabetes mellitus was
      demonstrated in the landmark Diabetes Control and Complications Trial that ended
      last year. In this article, Dr Hollander, who was a member of the study's
      multicenter research group, discusses the practical aspects of its key components
      and recommends methods of achieving glucose control in these patients.

PMID- 29211562
TI  - Diabetic ketoacidosis.
AB  - Preview Patients with diabetic ketoacidosis require immediate and aggressive
      therapy, but they may have confusing signs and symptoms. Patients are often warm
      and flushed despite having profound fluid depletion; they are seldom feverish but
      often have underlying infection. Dr Fish summarizes the clinical presentation of
      these patients, the four components of primary therapy, laboratory values to be
      monitored in tracking progress, and important details of follow-up.

PMID- 29211563
TI  - Pancreas transplantation for type I diabetes mellitus.
AB  - Preview Blindness, amputation, renal failure, premature coronary artery disease,
      disabling autonomic neuropathy: Most patients with type I diabetes mellitus must
      eventually confront one or more of these dire complications. However, carefully
      selected patients may benefit from the improved metabolic control provided by
      pancreas transplantation combined with kidney transplantation. According to the
      authors, the procedure is an exciting alternative to kidney transplantation alone
      or to dialysis.

PMID- 29211564
TI  - Is the "farm effect" hypothesis still current? Atopy and allergic diseases in
      rural and urban children in Poland.
AB  - OBJECTIVE: The prevalence of allergic diseases has reached epidemic proportions
      in the Western world. Although farm-living has been associated with a lower
      prevalence of asthma and atopy, a marked increase in atopy among rural
      populations after accession to the European Union has been recently reported in
      Poland. Here, we aimed to investigate the effect of living environment on the
      prevalence of atopy and allergic diseases in Polish children. METHODS: 400
      schoolchildren aged 10-14 years from the capital city (223) and from traditional
      rural part of the country (177) were recruited from June to November 2011. Data
      on allergic diseases and symptoms were collected by means of questionnaire and
      physical examination. Atopy was assessed based on skin prick tests (SPTs)
      reactivity to inhalant allergens in 350 children. RESULTS: A high discrepancy
      between the prevalence of allergic symptoms (46.7%) and doctor-diagnosed allergic
      diseases (25%) was demonstrated (p < 0.0001). Urban children had a higher overall
      prevalence of allergic diseases and atopy than children living in rural areas,
      29.3% versus 17.1% (p = 0.007) and 33.5% versus 20% (p = 0.0045), respectively.
      However, no significant differences in the rates of particular allergic diseases
      were noted (p > 0.05). There was higher SPT positivity to trees, grass, corn,
      weeds, animal dander, and molds in urban children (p < 0.05). CONCLUSIONS: Our
      data support the protective effect of farm-living on the prevalence of atopy and
      overall allergic diseases, albeit not on particular allergic diseases, in
      children in Poland. The underlying mechanisms are not identified, but current
      socioeconomic changes may be responsible.

PMID- 29211565
TI  - Myocardial infarction in the 1990s.
AB  - Preview A number of complications can be anticipated during the first hours and
      days after myocardial infarction. Some of these are due to the infarction itself,
      and others, such as intracranial hemorrhage, are a risk of the lifesaving
      thrombolytic therapy that a patient may be receiving. In this article, Dr Fowles
      describes the various complications associated with myocardial infarction,
      discusses prognosis and rehabilitation, and examines current management practices
      in the United States.

PMID- 29211566
TI  - Vertebral osteomyelitis.
AB  - Preview Bacterial infection of the spine is an uncommon disorder that causes the
      common symptom of back or neck pain. Prompt diagnosis and initiation of
      antimicrobial therapy are essential if patients are to avoid serious
      complications. What factors predispose some persons to vertebral osteomyelitis?
      Which imaging tools are most helpful in making the diagnosis and guiding biopsy
      or aspiration? The author answers these questions and discusses management
      options.

PMID- 29211567
TI  - Selling the Practice.

PMID- 29211568
TI  - Borderline personality disorder.
AB  - Preview Borderline personality disorder can be intriguing. The protagonists in
      Fatal Attraction, The Rose, and Play Misty for Me all provided dramatic examples.
      In a milder form, the disorder is seen fairly often in all medical settings. The
      authors review diagnostic characteristics of the disorder, how these show up in
      behavior during office visits, and tips for treating these challenging patients
      in the primary care setting.

PMID- 29211569
TI  - Acute severe asthma.
AB  - Preview How can the severity of an acute episode of asthma be assessed? What is a
      reasonable approach to corticosteroid administration in acute severe asthma? For
      which patients should mechanical ventilation be considered? The answers to these
      and other questions can be found in this guide to the evaluation and management
      of potentially fatal exacerbations of asthma.

PMID- 29211570
TI  - Physiologic evaluation of bronchial asthma.
AB  - Preview No physician would treat hypertension without monitoring blood pressure,
      but some treat bronchial asthma without objectively measuring pulmonary function.
      This empirical approach is inappropriate, according to the authors, who discuss
      key measurements that should be taken to assess disease status, guide therapy,
      and monitor response. Three illustrative cases stress the importance of objective
      evaluation of asthma.

PMID- 29211571
TI  - Occupational asthma.
AB  - Preview Patients affected by occupational asthma have respiratory symptoms that
      may persist for months, years, or even life. Hundreds of substances have been
      implicated in the disease, and the list is expected to grow. The authors discuss
      management of this sometimes life-threatening condition and emphasize the
      importance of environmental controls to prevent future cases.

PMID- 29211572
TI  - Nocturnal asthma and exercise-induced bronchospasm.
AB  - Preview More than two thirds of all patients with asthma struggle with nocturnal
      worsening of their symptoms, exercise-induced bronchoconstriction, or both.
      Understanding the causes of these problems provides a basis for controlling
      symptoms. Drs Wright and Martin elucidate those causes and make practical
      recommendations for minimizing nocturnal asthma and increasing patients' ability
      to exercise.

PMID- 29211573
TI  - Adolescent sexual intercourse.
AB  - Preview As sex, drugs, and rock 'n' roll have given way to STDs, HIV, and AIDS,
      adolescent sex has become an increasingly high- risk behavior. Dr Kay strongly
      believes that primary care physicians can have a prominent role in educating
      teens and their parents about the consequences of premature sexual activity and
      in promoting healthy living. In this article, he presents the case against
      adolescent sexual intercourse and outlines a concrete approach to dealing with
      adolescent patients at risk and their families.

PMID- 29211574
TI  - Peripheral arterial disease.
AB  - Preview Methods of evaluating and managing peripheral arterial disease have
      undergone significant changes in the last several years. In this article, Drs
      Krikorian and Vacek examine the place that angioplasty and other percutaneous
      techniques have taken in the treatment of atherosclerotic arterial disease
      affecting the lower extremities.

PMID- 29211575
TI  - Trichinosis.
AB  - Preview The incidence of many infectious diseases has declined as a result of
      modern sanitation, disease surveillance programs, and other public health
      measures. Trichinosis, however, continues to occur at a frequency that merits
      awareness by physicians. Dr Stack describes a case linked to homemade pork
      sausage and reviews current factors in epidemiology, diagnosis, and treatment of
      this uncommon but still troublesome disease.

PMID- 29211576
TI  - Development of a Web-Based Psychosocial Intervention for Adolescent and Young
      Adult Survivors of Pediatric Brain Tumor.
AB  - PURPOSE: To develop A Survivor's Journey, a web-based psychosocial intervention
      for adolescent and young adult (AYA) survivors of pediatric brain tumors (PBTs).
      METHODS: Stages of development included focus groups with five AYA survivors
      (ages 16-23 years) and six parents to identify needs and challenges, as well as
      surveys and interviews with clinical care providers at a survivorship clinic.
      RESULTS: Concerns reported by AYA survivors, parents, and providers were similar
      to those reported in the literature, including fatigue, memory deficits, poor
      mood, health concerns, and challenging peer relationships. However, concerns
      varied across survivors, underscoring the need for customizable interventions.
      Survivors and parents were interested in an intervention targeting psychosocial
      functioning and late effects, and reported a strong preference for web-based
      interventions that would reduce cost and travel burden on the family.
      INTERVENTION: Based on review of the literature, survivor and parent feedback, as
      well as provider input, a customizable intervention, A Survivor's Journey, was
      developed consisting of five core sessions (addressing concerns common to AYA
      survivors such as memory, staying positive, and problem solving) and up to seven
      supplemental sessions (addressing variable needs of survivors such as managing
      fatigue, inattention, planning/organization, communication/relationships, and
      self-care). CONCLUSION: Despite growing recognition of long-term challenges and
      late effects, there are few interventions targeting psychosocial well-being of
      AYA survivors. If efficacious, A Survivor's Journey will be an accessible and
      cost-effective intervention to improve psychosocial functioning of AYA survivors
      of PBT.

PMID- 29211578
TI  - Consensus?

PMID- 29211577
TI  - Measuring Quality Is Complicated.

PMID- 29211579
TI  - Healthcare for everyone, but how?
AB  - What system will ensure that all Americans can get medical care? How should it be
      financed? Can a standard benefits package ever be fair? Is a national health
      board a good idea? Recently, POSTGRADUATE MEDICINE arranged an exclusive exchange
      at the National Press Club in Washington, DC, between two senior fellows from
      groups that study such issues, with Glen C. Griffin, MD, asking the questions.
      The liberal viewpoint was represented by Marilyn Moon of the Urban Institute and
      the conservative viewpoint was represented by Peter Ferrara of the National
      Center for Policy Analysis.

PMID- 29211580
TI  - Tort reform, but what?
AB  - Nearly every healthcare reform plan introduced in Congress this year addresses
      medical malpractice. Although the tort reform goals in the plans may be similar,
      the methods of achieving them differ substantially. To highlight the areas that
      need to be resolved, we set up a dialogue between a physician and a plaintiff's
      attorney. The differing perspectives of Edward R. Annis, MD, former president of
      the American Medical Association, and Barry J. Nace, JD, past president of the
      Association of Trial Lawyers of America, exemplify the challenges legislators
      face.

PMID- 29211581
TI  - Can a managed care market work?
AB  - Has private practice medicine already died? Would government price controls on
      physician fees and hospital budgets contain medical costs? Should insurance
      coverage be reserved for catastrophic medical expenses? Dr Berenson gives his
      views on these questions and takes a realistic look at managed competition.

PMID- 29211582
TI  - Will the quality of US healthcare survive?
AB  - Should patients have the right to choose high-quality medical care? Yes, says the
      author, who explains how tax-free medical savings accounts and high-deductible
      insurance policies can help cut costs and allow patients and physicians to make
      their own decisions on minor medical problems. He also examines what he sees as
      the restrictions of managed care and discusses how the too liberal use of
      advanced technology can lead to "silent rationing."

PMID- 29211583
TI  - End-of-Life Care in Nursing Homes: A Qualitative Interpretive Meta-Synthesis.
AB  - BACKGROUND: Due to large number of deaths occurring in nursing home (NH)
      settings, along with reports of pain and suffering, there is great need for
      improvements in the provision of end-of-life (EOL) care in NHs. OBJECTIVE: The
      aim of this study was to develop a comprehensive understanding of the experience
      of dying in NHs through the perspective of residents, family, and facility staff.
      DESIGN: This study uses a qualitative interpretive meta-synthesis to provide a
      holistic view of EOL care in NHs across multiple qualitative studies.
      SETTING/SUBJECTS: Researchers synthesized the findings of 13 qualitative
      articles, including the diverse perspective of 91 dying residents, 419 NH staff,
      and 156 family members/caregivers across at least 44 NHs. METHODS: A qualitative
      meta-synthesis employs the following steps: identification of studies, theme
      extraction, translation, and synthesis of findings. RESULTS: Thematic analysis is
      organized using a conceptual model demonstrating the links between environmental
      and personal factors impacting EOL care in NHs. CONCLUSIONS: Findings provide
      support for the importance of a relational community and culture change within
      NHs for positive EOL experiences, in addition to providing a model to guide
      future research priorities.

PMID- 29211584
TI  - Helicobacter pylori infection.
AB  - Preview Since the discovery of Helicobacter pylori 10 years ago, its role in
      peptic ulcer disease has been recognized. Now the questions are, What is the best
      way to eradicate the organism, and which patients should receive treatment? Dr
      Anderson explores the issues concerning H pylori infection in patients with
      recurrent ulcers and describes the most reliable treatment regimens available.

PMID- 29211585
TI  - Acid reduction in peptic ulcer disease.
AB  - Preview Previously accepted methods of treating peptic ulcers have been pushed
      into the background by advances in drug therapy. In many cases, current therapy
      boils down to the question, Should I prescribe a histamine2 blocker or proton
      pump inhibitor? Several factors have to be considered in making the choice, among
      them the history and lifestyle of the particular patient. Dr Parent describes the
      characteristics of available agents and how to choose the most appropriate one.

PMID- 29211586
TI  - Use of NSAIDs.
AB  - Preview Certain populations, particularly the elderly, are vulnerable to
      complications from the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
      Rates of hospital admission for perforated ulcer are rising in these patients,
      who have an associated risk of gastrointestinal hemorrhage and death. Studies
      have shown that some NSAIDs cause less harm to the stomach and duodenum than
      others and that prostaglandin E analogues given concomitantly may protect the
      mucosa.

PMID- 29211587
TI  - Chronic fatigue syndrome update.
AB  - Preview Recent research on chronic fatigue syndrome has been directed toward
      understanding the mechanism of symptom production rather than uncovering the
      underlying cause of the illness. Abnormalities of immune function, hypothalamic
      and pituitary function, neurotransmitter regulation, and cerebral perfusion have
      been found in patients with the syndrome. Dr Bell summarizes and discusses the
      implications of these and other findings.

PMID- 29211588
TI  - Infectious vaginitis.
AB  - Preview Until recently, vaginal candidiasis was generally managed with topical
      preparations, whereas trichomoniasis and bacterial vaginosis required systemic
      therapy. Now both topical and systemic therapies are available for vaginal
      candidiasis and bacterial vaginosis, although systemic therapy is still
      recommended for trichomoniasis. This article reviews considerations in selecting
      the most appropriate therapy, including drug efficacy, history of recurrence,
      ease of administration, and cost.

PMID- 29211589
TI  - Hypertension in the diabetic patient.
AB  - Preview When diabetes and hypertension occur in the same patient, good control of
      both is needed to slow the progression of atherosclerosis and diabetic
      nephropathy. Antihypertensive agents must be selected with caution, as they may
      have side effects that are detrimental to diabetic patients. Drs Kochar and
      Kalluru review the types of hypertension that are common with diabetes and
      discuss both lifestyle modifications and pharmacologic therapy.

PMID- 29211591
TI  - These were a Few of My Favorite Things.

PMID- 29211590
TI  - Drug-induced meningitis.
AB  - Preview Drug-induced aseptic meningitis is an unusual adverse reaction associated
      with a number of medications. In this report, the authors present a case related
      to use of trimethoprim- sulfamethoxazole and summarize the available data
      regarding various proposed mechanisms of drug-induced meningitis. The usual
      clinical presentation and course of the disorder are discussed.

PMID- 29211592
TI  - Quality of Diabetes Care for Individuals with Comorbid Chronic Psychotic Illness:
      A Sex-Based Analysis.
AB  - BACKGROUND: Diabetes is common among individuals with chronic psychotic illness,
      yet they receive lower quality of diabetes care than those without psychosis. Men
      usually receive higher quality diabetes care than women, but whether this holds
      true in chronic psychotic illness populations is unknown. We aimed to determine
      whether quality of diabetes care differs between men and women with chronic
      psychotic illness. METHODS: This population-based cohort study used Ontario
      health administrative data to compare women and men with comorbid chronic
      psychotic illness and diabetes mellitus (2011-2013). The primary outcome was
      adherence to diabetes monitoring guidelines, defined as >=1 retinal exam, >=4
      hemoglobin A1c (HbA1c) tests, and >=1 dyslipidemia test during a 2-year period.
      Logistic regression models compared women to men to generate adjusted odds ratios
      (aOR) and confidence intervals (95% CI), adjusting for potential confounding
      variables. RESULTS: Women with chronic psychotic illness (n = 13,972) were
      slightly more likely to receive guideline-adherent diabetes monitoring than men
      (n = 12,287) (25.2% vs. 23.0%; aOR 1.20, 95% CI 1.10-1.30), including a greater
      likelihood of receiving >=1 retinal exam (aOR 1.13, 95% CI 1.08-1.19) and >=4
      HbA1c tests (aOR 1.06, 95% CI 1.01-1.12). There was no difference in receipt of
      >=1 dyslipidemia test (aOR 1.04, 95% CI 0.99-1.11). CONCLUSIONS: Quality of
      diabetes monitoring is similarly poor in women and men with chronic psychotic
      illness, with women receiving only marginally more optimal monitoring than men.
      This differs from patterns in the general population, and could have implications
      when designing and implementing interventions to improve diabetes care in women
      and men with chronic psychotic illness.

PMID- 29211593
TI  - Improvement in Ocular Bioavailability and Prolonged Delivery of Tobramycin
      Sulfate Following Topical Ophthalmic Administration of Drug-Loaded Mucoadhesive
      Microparticles Incorporated in Thermosensitive In Situ Gel.
AB  - PURPOSE: Conventional topical delivery in hyperacute bacterial conjunctivitis and
      endophthalmitis is associated with low drug bioavailability due to rapid
      precorneal clearance. Hence, in the present investigation, an attempt has been
      made to enhance ocular bioavailability of tobramycin sulfate by formulating drug
      loaded microparticles dispersed in thermosensitive in situ gel. METHODS:
      Microparticles prepared by emulsion-ionic gelation technique were characterized
      for drug loading, entrapment efficiency, particle size, surface morphology, and
      in vitro drug release. Consequently microparticles (F2 prepared with 1.5%w/v
      chitosan, 0.2%w/v tripolyphosphate, and drug, 30%w/w of polymer) with high drug
      loading and encapsulation efficiency were dispersed in thermosensitive in situ
      gel containing poloxamer 407 and varying percentage of chitosan. In situ gel
      containing drug-loaded microparticles were evaluated for gelation temperature,
      rheological behavior, mucoadhesive strength, in vitro drug release, in vitro
      permeation, ocular irritation, and bioavailability in aqueous humor of rabbits.
      RESULTS: Formulation containing 17%w/v poloxamer 407 and 0.5%w/v chitosan (P2)
      gelled at 32 degrees C +/- 1.5 degrees C gave pseudoplastic behavior. In vitro
      permeability of tobramycin from the formulation P2 was found 2-folds greater than
      eye drops. It also gave significantly higher aqueous humor concentration of
      tobramycin compared with eye drops with no signs of ocular irritation.
      CONCLUSION: Thus, the formulation possesses high potential for treating ocular
      infections.

PMID- 29211594
TI  - Compliance with Postpartum Diabetes Screening Recommendations for Patients with
      Gestational Diabetes.
AB  - BACKGROUND: The role of provider type and level of training have not been
      examined in regard to impact on postpartum testing for patients with gestational
      diabetes mellitus (GDM). OBJECTIVE: We sought to determine rates of testing in
      urban GDM patients and to determine factors associated with diabetes screening
      compliance, focusing especially on provider type. METHODS: Class A1 or A2 GDM
      patients were identified by chart review. Outcomes included ordering and/or
      performance of postpartum testing for diabetes mellitus. Chi-squared and
      multivariate logistic regression analyses were performed. RESULTS: Of the 118
      patients identified (55% class A1), 58% were African American, 52% had medical
      assistance insurance, and 83% attended the postpartum visit. Diabetes testing was
      discussed at 68% of all postpartum visits, but was only ordered at 55% of visits.
      The 2-hour glucose tolerance test was ordered at 42 of the 98 (43%) of postpartum
      visits; however, only 16 tests were completed. Patients seeing resident
      physicians or midwives were more likely to be tested. CONCLUSIONS: Rates of
      postpartum testing for GDM patients are low. Provider and patient compliance with
      diabetes screening recommendations are inadequate. Increased education and
      training of providers and patients may improve screening for diabetes among GDM
      patients.

PMID- 29211595
TI  - A survival kit for physicians.
AB  - "Just about the time you think you can make both ends meet, somebody moves the
      ends." As this aphorism implies, this is a time of anxiety and frustration,
      particularly for physicians who are caught up in the stresses and pressures of a
      changing healthcare system. Doublespeak from Washington and insurance companies
      adds to the confusion. But wait, says the author, there are strategies for
      coping, and he offers a number of suggestions to help ease physicians' lives in
      and out of the office.

PMID- 29211596
TI  - Who, me? An employee?
AB  - Politicians may have written a temporary obituary for healthcare reform, but as
      anyone in medicine knows, reform is alive and (debatably) well. Mergers,
      acquisitions, and practice changes are happening all across the land, and many a
      physician is going from being a small-business owner to being an employee.
      Difficult choices lie ahead that could affect the setting in which you practice,
      the way you practice, and the amount and way you are paid. Dr Rodeghero, a health
      compensation analyst and consultant, examines reform from the viewpoint of
      physician compensation.

PMID- 29211597
TI  - What now-move? merge? retire? stay put?
AB  - Most everyone is well versed about what's happening in Washington and probably in
      his or her own state capital regarding healthcare refonn, but what's happening at
      the grassroots level-with docs in the trenches? Just how has all the tunnoil
      affected you, your practice, your patients, and your future plans? The answers
      are surely as varied as the number of physicians reading these words. We
      interviewed four physicians from different areas and practice settings to get
      their answers and impressions. Participants were Barton J. Romanek, MD, of
      Lockhart, Texas; Timothy S. Komoto, MD, of Minneapolis; Dominic B. Brune, MD, of
      Zanesville, Ohio; and Philip P. Bonanni, MD, of Rochester, New York.

PMID- 29211598
TI  - Healthcare reform wars.
AB  - What's wrong with the current healthcare system, and who's to blame? How can
      government-run healthcare be avoided? Dr Moffit, from The Heritage Foundation in
      Washington, DC, analyzes the problems of the current system, explains the
      pitfalls of proposed reforms, and offers a solution for saving the traditional
      private practice system.

PMID- 29211599
TI  - Quantitation of salbutamol using micro-volume blood sampling - applications to
      exacerbations of pediatric asthma.
AB  - OBJECTIVES: A novel gas chromatography-mass spectrometry (GC-MS) method has been
      developed to quantify salbutamol in micro-volumes (10 uL) of blood. A potential
      application is paediatric therapeutic dose monitoring (TDM) in acute severe
      asthma. METHODS: At presentation, the children receive multiple doses of
      salbutamol (inhaled, nebulised and occasionally intravenous) but it is difficult
      to distinguish children who do not respond to treatment because of inadequate
      concentrations from those with toxicity, as symptoms are similar. A comparison
      was made between traditional dried blood spots (DBS) and the newly developed
      technique volumetric absorptive micro-sampling (VAMS), with specific
      investigation into the effect of drying time on analyte recovery. RESULTS: For
      both sampling techniques, the final assay demonstrated good precision and
      accuracy across the concentration range tested (3-100 ng/mL), including both the
      normal therapeutic and toxic range. The method was developed to comply with FDA
      guidelines with precision and accuracy <=15% for all concentrations, except the
      limit of quantification (5 ng/mL) where they were <=20%. VAMS offered advantages
      in sampling ease and reduced GC-MS interference. The assay was successfully
      applied to the quantification of blood salbutamol concentrations in three healthy
      volunteers dosed with 1 mg salbutamol by inhalation. CONCLUSIONS: This
      demonstrated its potential for use in paediatric TDM studies, where in the acute
      situation considerably higher doses of salbutamol will have been administered.
      This is the first time that a TDM method for salbutamol has been carried out
      using VAMS and offers all the advantages provided by DBS, whilst eliminating the
      inherent sampling volume inaccuracies of traditional DBS collection.

PMID- 29211601
TI  - Maintenance therapy for obstructive lung disease.
AB  - Preview In all cases of obstructive lung disease, smoking cessation, proper use
      of metered-dose inhalers, up-to-date immunizations, adequate nutrition, and
      general physical conditioning are important components of treatment. Dr Jacobs
      summarizes these components as well as stepwise pharmacologic approaches to
      controlling the inflammation of asthma, the bronchospasm of chronic bronchitis
      and emphysema, and the symptoms of secondary or coexisting conditions.

PMID- 29211600
TI  - Understanding the bone marrow microenvironment in hematologic malignancies: A
      focus on chemokine, integrin, and extracellular vesicle signaling.
AB  - Signaling between leukemia cells and nonhematopoietic cells in the bone marrow
      microenvironment contributes to leukemia cell growth and survival. This
      complicated extrinsic mechanism of chemotherapy resistance relies on a number of
      pathways and factors, some of which have yet to be determined. Research on cell
      cell crosstalk the bone marrow microenvironment in acute leukemia was presented
      at the 2016 annual Therapeutic Advances in Childhood Leukemia (TACL) investigator
      meeting. This review summarizes the mini-symposium proceedings and focuses on
      chemokine signaling via the cell surface receptor CXCR4, adhesion molecule
      signaling via integrin alpha4, and crosstalk between leukemia cells and the bone
      marrow microenvironment that is mediated through extracellular vesicles.

PMID- 29211602
TI  - Acute exacerbations of obstructive lung disease.
AB  - Preview Because they are rapidly effective, inhaled beta2 agonists are the
      cornerstone of therapy in patients having an acute exacerbation of obstructive
      lung disease. In addition, inhaled anticholinergics, methylxanthines, systemic
      corticosteroids, and antibiotics are useful in appropriate situations. The
      authors describe assessment of these patients (who may be critically ill at
      presentation), provide recommendations for conventional therapy, and summarize
      alternative methods.

PMID- 29211603
TI  - Lumbar puncture and CSF examination.
AB  - Preview Dr Morgenlander provides answers to some of the questions primary care
      physicians may have about lumbar puncture and cerebrospinal fluid (CSF)
      examination: What can be done to prevent post-lumbar puncture headache and how
      should it be treated? Does CSF pleocytosis in a patient who has had a seizure
      necessarily signify an underlying infectious or inflammatory process? Should
      every patient with dementia undergo CSF examination?

PMID- 29211604
TI  - Wilson's disease.
AB  - Preview An anxious, paranoid, disoriented patient usually requires psychiatric
      referral. Occasionally, such features are the first noticeable indication of an
      inherited copper-storage disorder. The authors describe accompanying hepatic and
      neurologic findings that characterize Wilson's disease and describe their recent
      experience in diagnosing and treating a patient with this uncommon disease.

PMID- 29211605
TI  - Renal adaptation to the failing heart.
AB  - Preview In patients with congestive heart failure, a diversity of neurohumoral
      and renal responses are involved in the maintenance of effective circuiting blood
      volume. The major clinical consequences of these responses are edema formation
      and, ultimately, decreased renal perfusion. In this article, the authors review
      the mechanisms that affect renal function in patients with systolic heart
      failure. A companion article on page 153 discusses use of therapeutic agents that
      modify these pathophysiologic sequelae.

PMID- 29211606
TI  - Renal adaptation to the failing heart.
AB  - Preview Selection of therapy for patients with systolic cardiac dysfunction must
      be predicated on careful assessment of the delicate interplay between the failing
      heart and the state of effective circulating blood volume. In this article, the
      authors discuss the drugs that improve systolic function and effective
      circulating volume and, ultimately, enhance tissue perfusion in vital organs such
      as the kidney. A companion article on page 141 explains the renal and
      neurohumoral events that occur in patients with systolic heart failure.

PMID- 29211608
TI  - Sliding Home.

PMID- 29211607
TI  - Acute polyarthritis.
AB  - Preview Although erythema infectiosum occurs primarily in children, the infection
      may be responsible for acute arthritis or arthralgia in adults. In this article,
      a case of acute symmetric polyarthritis affecting one of the authors is
      described. His symptoms were caused by parvovirus B19 infection, which was
      probably acquired from one of his children who had had erythema infectiosum a
      short time earlier.

PMID- 29211609
TI  - Effective use of insulin.
AB  - Preview Day-to-day control of diabetes demands an ongoing balance of diet,
      exercise, and insulin dosage that can only be achieved with regular self blood
      glucose monitoring. Patients need to be familiar with factors that affect the
      action of insulin and to know that "less is sometimes more." In this article, Dr
      Bohannon explains the simple concepts that lead to the most effective use of
      insulin.

PMID- 29211610
TI  - Diagnosing obstructive lung disease.
AB  - Preview There is considerable overlap in features and treatment of chronic
      obstructive pulmonary disease and asthma. Why, then, is it necessary to
      distinguish between the two? As the authors explain, the two diseases have
      different causes, risk factors, and clinical courses. Correct diagnosis,
      described in this article, allows physicians to take measures that reduce
      exacerbations and to accurately assess progress.

PMID- 29211611
TI  - Pregnancy-associated plasma protein-A (PAPP-A) levels in patients with severe
      allergic asthma are reduced by omalizumab.
AB  - BACKGROUND: Remodeling is a crucial feature of severe asthma and may be
      associated with activation of the allergic cascade by immunoglobulin E (IgE).
      Omalizumab, an anti-IgE monoclonal antibody, effectively targets the severe
      allergic asthma phenotype. Pregnancy-associated plasma protein-A (PAPP-A) is an
      insulin-like growth factor binding protein-4 (IGFBP-4) protease, increasing local
      insulin-like growth factor (IGF)-1 concentrations, which in turn initiating a
      cascade involved in the regulation of cell growth, differentiation, and
      proliferation in various tissues. In the present study, we evaluated the effects
      of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe
      allergic asthma. METHODS: We studied 36 asthmatic subjects and 36 healthy
      controls. An ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit was
      used to measure serum PAPP-A levels, and routine commercial ELISA kits were
      employed to assess serum levels of IGF-1, IGFBP-4 in control subjects and
      asthmatic subjects before therapy (baseline) and after six months of omalizumab
      therapy in patients with severe asthma. RESULTS: Compared to control subjects,
      serum PAPP-A and IGFB-4 levels were significantly higher in asthmatic subjects
      (both p values < 0.001). However, the serum IGF-I levels of asthmatic subjects
      were similar to those of control subjects (p > 0.05). In asthma subjects, 6-month
      omalizumab treatment significantly decreased the serum PAPP-A (p < 0.001), IGF-I
      (p = 0.031), and IGFB4 (p = 0.025) levels. CONCLUSION: PAPP-A level may be a
      useful biomarker for predicting airway remodeling in patients with severe asthma
      receiving omalizumab, and may also reflect the response to treatment.

PMID- 29211612
TI  - Tension headaches.
AB  - Preview Many people know the "tight-hatband" feeling that can occur at the end of
      an anxiety-filled day. An over-the-counter analgesic and a good night's sleep
      usually take care of it. But sometimes, headaches recur often or last days, and
      stronger measures are required. Dr Trachtenbarg summarizes the criteria for
      diagnosing tension headaches and outlines a stepwise approach to use of analgesic
      and prophylactic medications that minimizes the potential for dependence.

PMID- 29211613
TI  - Hypertensive heart disease.
AB  - Preview Americans often think of coronary artery disease as the most common
      cardiac disorder, but hypertensive heart disease is estimated to occur in nearly
      three times more patients, affecting about 20 million Americans. The authors
      discuss current criteria for diagnosis of hypertensive heart disease, common
      manifestations, coexisting conditions, comparative sensitivity of diagnostic
      methods, and treatment goals.

PMID- 29211614
TI  - Automated blood pressure monitoring.
AB  - Preview Blood pressure measurements obtained through 24-hour automated monitoring
      are more reliable than office measurements and more strongly correlated with
      target-organ damage from hypertension. Yet broad use of automated monitoring
      remains controversial. The authors discuss areas of debate, explain why they
      favor broader use, and provide practical information for clinicians who want to
      try this relatively new technology.

PMID- 29211615
TI  - Gonadotropin-releasing hormone agonists.
AB  - Preview Gonadotropin-releasing hormone (GnRH) agonists will have a significant
      impact on the practice of medicine in the 1990s. These agents will likely be
      given to increasing numbers of patients, and primary care physicians themselves
      may wish to prescribe the drugs when appropriate. This article describes the use
      of GnRH agonists in the treatment of endometriosis, advanced prostate cancer, and
      precocious puberty.

PMID- 29211616
TI  - Hepatitis C virus.
AB  - Preview Research on the hepatitis C virus (HCV) is currently very active, and a
      continuous stream of advances is coming forth. In this article, the authors
      present some recent developments in epidemiology and diagnosis, examine the
      relationship of HCV infection to other medical disorders, and discuss the
      effectiveness of current drug therapy.

PMID- 29211619
TI  - Life on the Edge: A Comparative Study of Ecophysiological Adaptations of Frogs to
      Tropical Semiarid Environments.
AB  - A key goal of ecology and evolution is to understand the relative contributions
      of environment and history in determining the geographic distribution of
      organisms. For the Neotropical lowlands, where temperatures are similar across
      landscapes, we hypothesize that water balance may be a critical but understudied
      factor in determining the distribution of species. Amphibians are especially
      sensitive to variation in precipitation due to their permeable skin. Here we
      focused on lowland frogs of northwestern South America and investigated variation
      among 17 species in potentially important ecologically relevant performance
      variables related to water balance, testing for possible adaptations to semiarid
      conditions within species. We studied frogs from coastal xeric, savannah, and wet
      forest biomes under common laboratory conditions and quantified rates of
      evaporative water loss, rates of water uptake, and variation in water-searching
      behavior and performance. We found significant differences in all three
      performance variables among species even after accounting for shared evolutionary
      history. A phylogenetic ANCOVA showed that categorizing species by ecological
      habit (terrestrial vs. arboreal) explained much of the ecoperformance trait
      variation among species. Secondarily, environment explained additional variation;
      for example, coastal xeric species showed reduced rates of water loss, and
      terrestrial savannah amphibians showed lower rates of water uptake. Conspecific
      frog populations from different biomes exhibited similar performance. We compare
      our results with previous studies and conclude that ecological habit is the
      principle factor that predicts ecophysiological trait variation and the possible
      geographic distribution of lowland Neotropical frogs.

PMID- 29211618
TI  - Outcome and Prognostic Factors in Stage III Favorable-Histology Wilms Tumor: A
      Report From the Children's Oncology Group Study AREN0532.
AB  - Background The National Wilms Tumor Study (NWTS) approach to treating stage III
      favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine,
      dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification
      is required to improve outcomes and reduce late effects. We evaluated clinical
      and biologic variables for patients with stage III FHWT without combined loss of
      heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children's Oncology
      Group protocol AREN0532. Methods From October 2006 to August 2013, 588
      prospectively treated, centrally reviewed patients with stage III FHWT were
      treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was
      determined by microsatellite analysis. Ineligible patients (n = 5) and those with
      combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with
      stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to
      9.5). Four-year event-free survival (EFS) and overall survival estimates were 88%
      (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of
      66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36).
      Eighteen patients died, 14 secondary to disease. A better EFS was associated with
      negative lymph node status ( P < .01) and absence of LOH 1p or 16q ( P < .01),
      but not with gross residual disease or peritoneal implants. In contrast, the 4
      year EFS was only 74% in patients with combined positive lymph node status and
      LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted
      delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival
      analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk
      (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses).
      Conclusion Most patients with stage III FHWT had good EFS/overall survival with
      DD4A and radiation therapy. Combined lymph node and LOH status was highly
      predictive of EFS and should be considered as a potential prognostic marker for
      future trials.

PMID- 29211617
TI  - Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell
      Nuclear Atrophy and Apoptosis After Optic Nerve Injury.
AB  - PURPOSE: HDAC3 regulates nuclear atrophy as an early response to axonal injury in
      retinal ganglion cells (RGCs) following optic nerve crush (ONC). Since
      conditional knockout of Hdac3 prevents nuclear atrophy post ONC, HDAC3 selective
      inhibition with RGFP966 through localized and systemic dosing of RGFP966 is
      necessary for application to acute and chronic models of optic nerve injury.
      METHODS: C57BL/6 mice were injected intravitreally with 1-10 MUM RGFP966
      immediately following ONC, and retinas were analyzed at 5, 7, and 14 days for
      metrics of nuclear atrophy and cell loss. Mice were similarly assessed after
      intraperitoneal (IP) injections with RGFP966 doses of 2-10 mg/kg, and eyes were
      harvested at 5, 14, and 28 days after ONC. H&E and BrdU staining were used to
      analyze toxicity to off-target tissues after 14 days of daily treatment with
      RGFP966. RESULTS: A single intravitreal injection of RGFP966 prevented histone
      deacetylation, heterochromatin formation, apoptosis, and DNA damage at 5 and 7
      days post ONC. After IP injection, RGFP966 bioavailability in the retina reached
      peak concentration within 1 h after injection and then rapidly declined. A single
      IP injection of 2-10 mg/kg RGFP966, significantly prevented histone
      deacetylation. Repeated IP injections of 2 mg/kg RGFP966 over the course of 2 and
      4 weeks post ONC prevented RGC loss. There were no significant toxic or
      antiproliferative effects to off-target tissues in mice treated daily for 14 days
      with RGFP966. CONCLUSION: Inhibition of HDAC3 activity with systemic dosing of
      RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss
      after acute optic nerve injury.

PMID- 29211620
TI  - Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior
      quadrivalent HPV vaccine recipients and in men 16 to 26 years of age.
AB  - A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type
      6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses
      from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age,
      including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and
      women 16-26 years of age, showed that the 9vHPV vaccine was generally well
      tolerated. Additional safety analyses were conducted to include the results of
      new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV
      vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label
      extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine
      recipients from 1 randomized controlled trial) was evaluated. Vaccine was
      administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse
      events (AEs) were monitored. The most common AEs were injection-site events
      (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively),
      the majority of which were mild. Discontinuations due to an AE were rare (0.2%
      and 0.0% among prior qHPV vaccine recipients and young men, respectively). In
      young men, the AE profile of the 9vHPV vaccine was generally similar to that of
      the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in
      prior qHPV vaccine recipients and in young men, with an AE profile generally
      consistent with that previously reported with the broader clinical program.

PMID- 29211622
TI  - Hepatitis A Outbreak in California - Addressing the Root Cause.

PMID- 29211621
TI  - Delayed measles vaccination of toddlers in Canada: Associated socio-demographic
      factors and parental knowledge, attitudes and beliefs.
AB  - Delaying vaccination increases the period of vulnerability of children against
      vaccine-preventable diseases. We used a nationally representative sample of
      Canadian two-year-old children to explore factors associated with delays in the
      uptake of the first dose of measles-containing vaccine, recommended in Canada for
      children at 12 months of age. Distribution of delays was determined using data
      from the 2013 Childhood National Immunization Coverage Survey. Logistic
      regression was used to examine sociodemographic factors and knowledge, attitudes
      and beliefs (KAB) associated with the two outcomes of interest: delays of one to
      six months (vaccination at 13 to 18 months of age) and delays of seven to 18
      months (vaccination at 19 to 23 months of age). Overall, 69% (95% confidence
      interval [CI] 67-71) of children received their first valid dose on time. Twenty
      nine percent (95% CI 27-31) and 11% (95% CI 9-12) of children were unvaccinated
      before turning 13 and 16 months of age, respectively. Factors associated with
      delays of one to six months were being a girl, being born outside Canada, and the
      jurisdiction of residence. Being from a single-parent family, being born outside
      Canada and the jurisdiction of residence were associated with delays of seven to
      18 months, suggesting that potential barriers might be at play. Associations
      between KAB and vaccination delays indicate that vaccine hesitancy could
      contribute to measles vaccination delays in Canada. Barriers in accessing
      vaccination services and the role of vaccine hesitancy in timely vaccination must
      be better understood to reduce vaccination delays in toddlers in Canada.

PMID- 29211623
TI  - Quality of Care Improves for Patients with Diabetes in Medicare Shared Savings
      Accountable Care Organizations: Organizational Characteristics Associated with
      Performance.
AB  - Accountable care organizations (ACOs), a primary care-centric delivery and
      payment model, aim to promote integrated population health, which may improve
      care for those with chronic conditions such as diabetes. Research has shown that,
      overall, the ACO model is effective at reducing costs, but there is substantial
      variation in how effective different types of ACOs are at impacting costs and
      improving care delivery. This study examines how ACO organizational
      characteristics - such as composition, staffing, care management, and experiences
      with health reform - were associated with quality of care delivered to patients
      with diabetes. Secondary data were analyzed retrospectively to examine Medicare
      Shared Savings Program (MSSP) ACOs' performance on diabetes metrics in the first
      2 years of ACO contracts. Ordinary least squares was used to analyze 162 MSSP
      ACOs with publicly available performance data and the National Survey of ACOs.
      ACOs improved performance significantly for patients with diabetes between
      contract years 1 and 2. In year 1, also having a private payer contract and an
      increased number of services within the ACO were positively associated with
      performance, while having a community health center or a hospital were negatively
      associated with performance. Better performance in year 1 was negatively
      associated with improved performance in year 2. This study found that ACOs
      substantively improved diabetes management within initial contract years. ACOs
      may need different types of support throughout their contracts to ensure
      continued improvements in performance.

PMID- 29211624
TI  - Vaccine prevention of meningococcal disease in Africa: Major advances, remaining
      challenges.
AB  - Africa historically has had the highest incidence of meningococcal disease with
      high endemic rates and periodic epidemics. The meningitis belt, a region of sub
      Saharan Africa extending from Senegal to Ethiopia, has experienced large,
      devastating epidemics. However, dramatic shifts in the epidemiology of
      meningococcal disease have occurred recently. For instance, meningococcal
      capsular group A (NmA) epidemics in the meningitis belt have essentially been
      eliminated by use of conjugate vaccine. However, NmW epidemics have emerged and
      spread across the continent since 2000; NmX epidemics have occurred sporadically,
      and NmC recently emerged in Nigeria and Niger. Outside the meningitis belt, NmB
      predominates in North Africa, while NmW followed by NmB predominate in South
      Africa. Improved surveillance is necessary to address the challenges of this
      changing epidemiologic picture. A low-cost, multivalent conjugate vaccine
      covering NmA and the emergent and prevalent meningococcal capsular groups C, W,
      and X in the meningitis belt is a pressing need.

PMID- 29211625
TI  - Anterior Inferior Iliac Spine Deformity as a Cause for Extra-articular Hip
      Impingement in Young Athletes After an Avulsion Fracture: A Case Report.
AB  - Extra-articular hip impingement from prior traumatic injury to the anterior
      inferior iliac spine (AIIS) is an uncommon cause of groin pain in young athletes.
      Currently, the most common treatment for this injury is arthroscopic
      decompression. However, hip arthroscopy is not universally available and requires
      advanced skills. We report 2 cases of the development of extra-articular hip
      impingement from unusual bony exostoses off the AIIS after traumatic injury in 2
      young athletes who underwent open surgical resection. The multidisciplinary
      sports medicine team should be aware of the development of extra-articular
      impingement from traumatic injury to the AIIS and that open surgical resection is
      a viable alternative to arthroscopic decompression.

PMID- 29211626
TI  - Molecular analyses uncover the phylogenetic placement of the lichenized
      hyphomycetous genus Cheiromycina.
AB  - The genus Cheiromycina is one of the few genera of lichenized hyphomycetes for
      which no sexual reproductive stages have been observed. The genus includes
      species from boreal to temperate regions of the Northern Hemisphere where it is
      found growing on bark or wood. Congeners in Cheiromycina are characterized by a
      noncorticate thallus, nearly immersed in the substrate and presenting powdery
      unpigmented sporodochia, and containing chlorococcoid photobionts. The
      relationships of members of Cheiromycina with other fungi are not known. Here we
      inferred the phylogenetic placement of Cheiromycina using three loci (nuSSU,
      nuLSU, and mtSSU) representing C. flabelliformis, the type species for the genus,
      C. petri, and C. reimeri. Our results revealed that the genus Cheiromycina is
      found within the family Malmideaceae (Lecanorales) where members formed a
      monophyletic clade sister to the genera Savoronala and Malmidea. This
      phylogenetic placement and the relationships of Cheiromycina with other
      lichenized hyphomycetous taxa are here discussed.

PMID- 29211627
TI  - Proprioceptive Flexible Fluidic Actuators Using Conductive Working Fluids.
AB  - Soft robotic systems generally require both soft actuators and soft sensors to
      perform complex functions. Separate actuators and sensors are often combined into
      one composite device when proprioception (self-sensing) is required. In this
      article, we introduce the concept of using a conductive liquid to perform both
      the sensing and actuation functions of a proprioceptive soft actuator. The
      working fluid drives actuator deformation while simultaneously acting as a strain
      sensing component for detecting actuator deformation. The concept is examined and
      demonstrated in two proprioceptive flexible fluidic actuators (FFAs) that use
      conductive liquids as their working fluids: a linear actuator and a bending
      actuator. In both cases, we show that resistance can be used to infer strain.
      Some hysteresis and nonlinearity are present, but repeatability is high. The
      bandwidth of resistance as a sensing variable in the bending FFA is tested and
      found to be ~3.665 Hz. Resistance is demonstrated as a feedback variable in a
      control loop, and the proprioceptive bending FFA is controlled to respond to step
      input and sinusoidal target functions. The effect of temperature on resistance
      strain behavior is also examined, and we demonstrate how measurement of volume
      and resistance can be used to detect when the actuator is constrained.
      Biocompatible proprioceptive soft actuators such as those presented in this
      article are ideal for use in low-cost bionic healthcare components such as
      orthotics, prosthetics, or even replacement muscles.

PMID- 29211628
TI  - Comparative expression analysis of starch degrading genes between dormant and non
      dormant wheat seeds.
AB  - To gain insights into the molecular basis of starch degradation in wheat seeds
      with respect to dormancy maintenance and release, this study compared the
      expression of starch degrading genes between dormant and after-ripened seeds in
      both dry and imbibed states. Furthermore, the study examined the effect of ABA on
      the expression of starch degrading genes during imbibition of non-dormant seeds.
      Release of dormancy due to after-ripening led to the upregulation of specific
      genes encoding alpha-amylase and alpha-glucosidase during imbibition while
      dormancy maintenance is associated with repression of these genes. It appears
      from our result that ABA delays the germination of wheat seeds at least partly
      through repression of the starch degrading genes.

PMID- 29211629
TI  - Report of the 5th European expert meeting on rotavirus vaccination (EEROVAC).
AB  - The Fifth European Expert Meeting on Rotavirus Vaccination was convened in
      Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited
      lectures as well as original oral and poster presentations and brought together
      experts from 21 countries. Summary findings of the meeting include: Rotavirus
      vaccination programmes in Europe have resulted in reductions of 60-90% in
      rotavirus outpatient visits and hospitalizations. Long term trends indicate this
      impact is sustained over the years. Herd effects, protecting unvaccinated
      children and neonates too young to be vaccinated have been observed in many
      European countries. Early evidence now also suggests that rotavirus vaccination
      may be instrumental in the prevention of celiac disease. Special attention should
      be given to preterm infants, who may age out of the vaccination window before
      hospital discharge and to HIV infected children who are at increased risk of
      severe rotavirus AGE. There is a small but increased risk of IS following
      rotavirus vaccination and parents should therefore be informed about possible
      signs and symptoms of IS. New insights in rotavirus genetic susceptibility and
      interactions with microbiome may open opportunities for interventions to improve
      protection by vaccination, in particular in LMIC. The development of several
      novel rotavirus vaccines discussed at the meeting is also promising in this
      respect.

PMID- 29211630
TI  - Production of Monoclonal Antibody That Recognizes Zika Virus and Other
      Flaviviruses in Serum-Free Conditions.
AB  - With the recent outbreaks of Zika and Dengue virus infections in various
      countries worldwide, production of vaccines or diagnostic kits is an urgent
      public health demand. Production of a monoclonal antibody (mAb) that specifically
      binds to a common antigen shared by the Flavivirus genus will be necessary for
      new diagnostic kits or characterization and viral identity tests during vaccine
      development. This study aimed to cultivate, in serum-free conditions, the 4G2
      hybridoma that produces an mAb, which recognizes a shared epitope from the
      Flavivirus genus. We compared 4G2 hybridoma growth and biochemical profiles
      between cells cultivated in batch mode over 10 days in roller bottles containing
      Dulbecco's modified Eagle's medium high glucose containing 10% fetal bovine serum
      medium or hybridomas directly adapted to Ex-Cell serum-free medium. Cellular
      parameters such as specific growth rate (MU), maximum cell concentration,
      specific l-lactate, and glucose and IgG rates were evaluated. Thereafter, we also
      compared total mAb volumetric productivity, purification yield, and mAb staining
      of Vero cells infected with Zika and Dengue-2 virus. Direct adaptation to serum
      free conditions did not change hybridoma growth rate and mAb production under the
      conditions tested. Instead, serum-free mAb purification showed a higher yield
      with no alterations on mAb structure or mAb staining of Zika and Dengue Vero
      infected cells.

PMID- 29211631
TI  - How to Measure Population Health: An Exploration Toward an Integration of Valid
      and Reliable Instruments.
AB  - Population health management initiatives are introduced to transform health and
      community services by implementing interventions that combine various services
      and address the continuum of health and well-being of populations. Insight is
      required into a population's health to evaluate implementation of these
      initiatives. This study aims to determine the performance of commonly used
      instruments for measuring a population's experienced health and explores the
      assessed concepts of population health. Survey-based Short Form 12, version 2
      (SF12, health status), Patient Activation Measure 13 (PAM13), and Kessler 10
      (K10, psychological distress) data of 3120 respondents was used. Floor/ceiling
      effects were studied using descriptive statistics. Validity was assessed using
      factor and discriminant analyses, and reliability was assessed using Cronbach
      alpha. Finally, to study covered concepts, exploratory factor analyses (EFAs)
      were conducted, which included additional surveyed characteristics. The SF12 and
      PAM13 sum scores showed acceptable averages and distributions, while results of
      the K10 indicated a floor effect. SF12 and K10 measured their expected
      constructs, while PAM13 did not. The EFA of PAM13 displayed 1 instead of the
      expected 4 constructs. Reliability was good for all instruments (alpha 0.89
      0.93). The overall EFA identified 4 concepts: mental, physical ability,
      lifestyle, and self-management. SF12 and PAM13, combined with lifestyle
      characteristics, are shown to provide insightful information to measure the
      physical, mental, lifestyle, and self-management concepts of population health.
      Future research should include additional instruments that cover new aspects
      introduced by recent definitions of health.

PMID- 29211632
TI  - An Employer Health Incentive Plan for Advance Care Planning and Goal-Aligned
      Care.
AB  - One strategy to promote workforce well-being has been health incentive plans, in
      which a company's insured employees are offered compensation for completing a
      particular health-related activity. In 2015, Providence Health & Services adopted
      an Advance Care Planning (ACP) activity as a 2015-2016 health incentive option.
      More than 51,000 employees and their insured relatives chose the ACP incentive
      option. More than 80% rated the experience as helpful or very helpful. A high
      proportion (95%) of employees responded that they had someone they trusted who
      could make medical care decisions for them, yet only 23% had completed an advance
      directive, and even fewer (11%) had shared the document with their health care
      provider. The most common reason given for not completing an advance directive
      was that health care providers had never asked about it. These findings suggest
      that an insured employee incentive plan can encourage ACP consistent with the
      health care organizations' values and strategic priorities.

PMID- 29211634
TI  - Risk assessment of benzalkonium chloride in cosmetic products.
AB  - A risk assessment of benzalkonium chloride (BAC) was conducted based upon its
      toxicological profile and exposure evaluation. Since 1935, BAC has been used in a
      wide variety of products such as disinfectants, preservatives, and sanitizers. It
      is well-established that BAC is not genotoxic nor does it display tumorigenic
      potential, but safety concerns have been raised in local usage such as for ocular
      and intranasal applications. The Foundation of Korea Cosmetic Industry Institute
      (KCII) reported that in a hair conditioner manufactured as a cosmetic or personal
      product in South Korea, BAC was present at concentrations of 0.5-2%. The systemic
      exposure dosage (SED) was determined using the above in-use concentrations and a
      risk assessment analysis was conducted. The Margin of Safety (MOS) values for
      hair conditioners were calculated to be between 621 and 2,483. The risk of
      certain personal and cosmetic products was also assessed based upon assumptions
      that BAC was present at the maximal level of regulation in South Korea and that
      the maximal amount was used. The MOS values for the body lotion were all above
      100, regardless of the application site. Collectively, data indicate that there
      are no safety concerns regarding use of products that contain BAC under the
      current concentration restrictions, even when utilized at maximal permitted
      levels. However, a chronic dermal toxicity study on BAC and comprehensive dermal
      absorption evaluation needs to be conducted to provide a more accurate prediction
      of the potential health risks to humans.

PMID- 29211633
TI  - Prevalence and patterns of victimization and polyvictimization among female sex
      workers in Soweto, a South African township: a cross-sectional, respondent-driven
      sampling study.
AB  - BACKGROUND: Female sex workers (FSWs) are disproportionately affected by violence
      from multiple partner categories. This increases their vulnerability to HIV.
      OBJECTIVES: To describe patterns of violence and polyvictimization among female
      SWs in Soweto. METHODS: A respondent-driven sampling (RDS) recruitment
      methodology was used to enrol 508 Soweto-based FSWs using a survey instrument.
      Raw and RDS adjusted data were descriptively analysed, Spearman's correlation and
      chi2 test of association were used to show associations. Polyvictimization
      patterns are shown within a modified Venn diagram. RESULTS: The median age of
      FSWs in Soweto was 31 years, and most had an incomplete education (74.2%). The
      prevalence of exposure to physical/sexual intimate partner violence (IPV) in the
      past year was 53.8%, 46.8% by clients, and 18.5% by police. Past year prevalence
      of sexual/physical violence by any perpetrator category was 70.8% and lifetime
      exposure was 76.0%. Childhood sexual violence was reported by 44.3%. Lifetime non
      partner rape was 55.5% and all rape exposure was 62.4%. As a result of engaging
      in sex work in the past year, 65.2% women had been discriminated against. Client,
      police, IPV, and childhood trauma were all significantly associated with one
      another, with IPV being the most common co-occurrence. Polyvictimization was seen
      in almost two-thirds of FSWs, and increased with exposure to discrimination.
      CONCLUSION: In Soweto, FSWs are exposed to high rates of violence in multiple
      forms across their lifetime. Our findings show that violence continues unabated
      into adulthood at levels far higher than in the general population and overall at
      higher levels than previously recorded among SWs in South Africa. We argue that
      violence against FSWs is rooted in discrimination. The disparate burden of
      violence on FSWs requires urgent interventions to proactively address and reframe
      the normalisation of violence against all women.

PMID- 29211635
TI  - Association of IL-13 rs20541 and rs1295686 variants with symptomatic asthma in a
      Saudi Arabian population.
AB  - OBJECTIVE: Interleukin 13 (IL-13) plays a critical pro-inflammatory role in
      asthma. Several single nucleotide polymorphisms (SNPs) are associated with asthma
      susceptibility in specific populations; however, further replicative studies in
      other ethnic groups are mandatory. METHODS: The association between IL-13 SNPs
      rs762534, rs20541, rs1295686, and rs1800925 (risk alleles A, A, T, and A,
      respectively) and asthma predisposition in a Saudi Arabian cohort was examined
      via a case-control cross-sectional study. RESULTS: The frequencies of alleles
      between asthmatics and control populations were significantly different for
      rs20541 and rs1295686 SNPs (p < 0.001), whereas the frequencies of genotypes
      between asthmatics and controls were significantly different only for rs20541.
      The association of the risk (minor) alleles with asthma was examined using the
      dominant genetic model. Individuals with at least one copy of the risk alleles A
      (for rs20541) and T (for rs1295686) had significantly greater odds of being
      asthmatic (OR = 2.13, 95% CI = 1.39-3.26, p < 0.0001; OR = 1.69, 95% CI = 1.12
      2.54, p = 0.008) relative to their most common homozygous genotypes. On the other
      hand, the minor A alleles for rs762534 and rs1800925 were not significantly
      associated with asthma risk. Regarding haplotype association analysis,
      individuals with at least one copy of the minor "risk" allele for both rs20541
      and rs1295686 (CATG and CATA, respectively) had greater odds of being asthmatic
      relative to CGCG haplotype; however, this trend was not statistically significant
      (p > 0.3). CONCLUSIONS: IL-13 minor T and A alleles for rs1295686 and rs20541,
      respectively, were associated with significantly higher risk of asthma in the
      Saudi Arabian population.

PMID- 29211636
TI  - Behavioral problems in nursing home residents.
AB  - Preview Thanks to advances in health awareness and medical care, the elderly
      population continues to grow. But with added years of life comes an increase in
      age-related cognitive impairment and resulting behavioral problems (eg,
      agitation, wandering) that must be addressed by institutions and physicians. The
      authors describe patient evaluation and summarize approaches for initial and
      continuing treatment of behavioral problems related to dementia.

PMID- 29211637
TI  - Pharyngitis.
AB  - Preview Depending on the cause, pharyngitis may be a relatively benign symptom or
      an ominous harbinger of severe sequelae, including rheumatic fever. Therefore,
      accurate diagnosis and appropriate treatment are important to avoid potentially
      serious complications. Drs Bonilla and Bluestone discuss the most common causes
      of pharyngitis, the diagnostic workup, and the current symptomatic and
      antimicrobial therapies. Treatment of recurrent tonsillitis is also included.

PMID- 29211638
TI  - Acute and chronic sinusitis.
AB  - Preview Sinusitis is often easily recognized by the familiar complaints of
      paranasal pressure, tenderness, and headaches. What is more difficult is sorting
      out viral, bacterial, or fungal infection from allergy, anatomic obstruction, or
      underlying disease. Dr Ferguson outlines signs and symptoms that differentiate
      various forms of rhinosinusitis, discusses strengths and weaknesses of diagnostic
      measures, and summarizes appropriate therapeutic interventions.

PMID- 29211639
TI  - The neck mass.
AB  - Preview Neck masses in children and young adults are often benign, whereas masses
      in adults, especially those over age 40, are commonly malignant. In either case,
      because of the intricate anatomic structures in the neck, physicians are
      confronted with an unusually broad and formidable array of possible diagnoses,
      which Drs Alvi and Johnson discuss in this article.

PMID- 29211640
TI  - Otitis media reassessed.
AB  - Preview Management of otitis media in children is a controversial matter: The
      basic questions of why, in whom, and how it should be treated are undergoing
      continual reassessment. In this article, Drs Shapiro and Bluestone provide
      answers to these and other questions, such as Why is treatment of acute otitis
      media justified? When is the "wait and see" approach to otitis media with
      effusion inadvisable? Which common treatment approaches are ineffective? When
      should referral to an otolaryngologist be considered?

PMID- 29211641
TI  - Urinary incontinence in the elderly.
AB  - Preview The incidence of incontinence in elderly men and women is high, and the
      personal and social costs of the problem are enormous. But thoughtful diagnostic
      evaluation can lead to treatment that in many cases results in an improvement in
      symptoms or even a return to continence. Dr Rosenthal and Dr McMurtry discuss
      five main types of incontinence and their causes and treatment and describe the
      components of a targeted medical evaluation.

PMID- 29211642
TI  - Severe gastroesophageal reflux disease.
AB  - Preview Medical and surgical choices for treating gastroesophageal reflux disease
      have never been better. In the last few years, potent medications have been
      introduced that suppress gastric acid production and have promotility effects,
      and laparoscopic approaches to antireflux surgery have been developed. In this
      article, Dr Marshall reviews current management techniques and explains how to
      decide which to recommend in a given patient with severe disease.

PMID- 29211643
TI  - Myocardial infarction in the 1990s.
AB  - Preview In the United States, cardiovascular disease still causes more deaths
      than any other health problem. This year, 1.5 million people will have myocardial
      infarctions, and many will die before they reach the hospital. In this article,
      Dr Fowles emphasizes the great need for expanded delivery of lifesaving
      thrombolytic agents.

PMID- 29211644
TI  - Henoch-Schonlein purpura.
AB  - Preview As the name implies, Henoch-Schonlein purpura is a vasculitic disease,
      but it also affects multiple organ systems. Although the exact cause of the
      disease has not been determined, recent studies have shed some light on its
      pathogenesis. This article reviews these studies and discusses the various
      manifestations and possible complications. Two classification systems are also
      included.

PMID- 29211645
TI  - A systematic approach to macrocytosis.
AB  - Preview Macrocytosis has causes other than folate or vitamin B12 deficiency,
      including chronic alcohol ingestion and various forms of drug therapy. In this
      article, Dr Brigden presents clinical cases that illustrate five different causes
      of macrocytosis, with comments on each case to facilitate the overall approach to
      diagnosis and management.

PMID- 29211646
TI  - MD/DO Jobs and Incomes May Shrink.

PMID- 29211647
TI  - No ice, no butter.
AB  - Preview It is often difficult to determine the true extent of a burn, but most
      small thermal burns can be easily evaluated and managed by primary care
      physicians. In this article, the authors review the characteristics of different
      types of bums, describe those that require treatment in a bum center, and discuss
      appropriate measures to hasten healing and promote a satisfactory cosmetic
      outcome.

PMID- 29211648
TI  - Are You Asking the Right Questions?

PMID- 29211649
TI  - Hearing Shapes: Event-related Potentials Reveal the Time Course of Auditory
      Visual Sensory Substitution.
AB  - In auditory-visual sensory substitution, visual information (e.g., shape) can be
      extracted through strictly auditory input (e.g., soundscapes). Previous studies
      have shown that image-to-sound conversions that follow simple rules [such as the
      Meijer algorithm; Meijer, P. B. L. An experimental system for auditory image
      representation. Transactions on Biomedical Engineering, 39, 111-121, 1992] are
      highly intuitive and rapidly learned by both blind and sighted individuals. A
      number of recent fMRI studies have begun to explore the neuroplastic changes that
      result from sensory substitution training. However, the time course of cross
      sensory information transfer in sensory substitution is largely unexplored and
      may offer insights into the underlying neural mechanisms. In this study, we
      recorded ERPs to soundscapes before and after sighted participants were trained
      with the Meijer algorithm. We compared these posttraining versus pretraining ERP
      differences with those of a control group who received the same set of 80
      auditory/visual stimuli but with arbitrary pairings during training. Our
      behavioral results confirmed the rapid acquisition of cross-sensory mappings, and
      the group trained with the Meijer algorithm was able to generalize their learning
      to novel soundscapes at impressive levels of accuracy. The ERP results revealed
      an early cross-sensory learning effect (150-210 msec) that was significantly
      enhanced in the algorithm-trained group compared with the control group as well
      as a later difference (420-480 msec) that was unique to the algorithm-trained
      group. These ERP modulations are consistent with previous fMRI results and
      provide additional insight into the time course of cross-sensory information
      transfer in sensory substitution.

PMID- 29211650
TI  - Selective Interference with Syntactic Encoding during Sentence Production by
      Direct Electrocortical Stimulation of the Inferior Frontal Gyrus.
AB  - Cortical stimulation mapping (CSM) has provided important insights into the
      neuroanatomy of language because of its high spatial and temporal resolution, and
      the causal relationships that can be inferred from transient disruption of
      specific functions. Almost all CSM studies to date have focused on word-level
      processes such as naming, comprehension, and repetition. In this study, we used
      CSM to identify sites where stimulation interfered selectively with syntactic
      encoding during sentence production. Fourteen patients undergoing left-hemisphere
      neurosurgery participated in the study. In 7 of the 14 patients, we identified
      nine sites where cortical stimulation interfered with syntactic encoding but did
      not interfere with single word processing. All nine sites were localized to the
      inferior frontal gyrus, mostly to the pars triangularis and opercularis.
      Interference with syntactic encoding took several different forms, including
      misassignment of arguments to grammatical roles, misassignment of nouns to verb
      slots, omission of function words and inflectional morphology, and various
      paragrammatic constructions. Our findings suggest that the left inferior frontal
      gyrus plays an important role in the encoding of syntactic structure during
      sentence production.

PMID- 29211651
TI  - Cortico-cerebellar Networks Drive Sensorimotor Learning in Speech.
AB  - The motor cortex and cerebellum are thought to be critical for learning and
      maintaining motor behaviors. Here we use transcranial direct current stimulation
      (tDCS) to test the role of the motor cortex and cerebellum in sensorimotor
      learning in speech. During productions of "head," "bed," and "dead," the first
      formant of the vowel sound was altered in real time toward the first formant of
      the vowel sound in "had," "bad," and "dad." Compensatory changes in first and
      second formant production were used as a measure of motor adaptation. tDCS to
      either the motor cortex or the cerebellum improved sensorimotor learning in
      speech compared with sham stimulation ( n = 20 in each group). However, in the
      case of cerebellar tDCS, production changes were restricted to the source of the
      acoustical error (i.e., the first formant). Motor cortex tDCS drove production
      changes that offset errors in the first formant, but unlike cerebellar tDCS,
      adaptive changes in the second formant also occurred. The results suggest that
      motor cortex and cerebellar tDCS have both shared and dissociable effects on
      motor adaptation. The study provides initial causal evidence in speech production
      that the motor cortex and the cerebellum support different aspects of
      sensorimotor learning. We propose that motor cortex tDCS drives sensorimotor
      learning toward previously learned patterns of movement, whereas cerebellar tDCS
      focuses sensorimotor learning on error correction.

PMID- 29211652
TI  - Changes in Frontoparietotemporal Connectivity following Do-As-I-Do Imitation
      Training in Chimpanzees ( Pan troglodytes).
AB  - Human imitation is supported by an underlying "mirror system" principally
      composed of inferior frontal, inferior parietal, and superior temporal cortical
      regions. Across primate species, differences in frontoparietotemporal
      connectivity have been hypothesized to explain phylogenetic variation in
      imitative abilities. However, if and to what extent these regions are involved in
      imitation in nonhuman primates is unknown. We hypothesized that "Do As I Do"
      (DAID) imitation training would enhance white matter integrity within and between
      frontoparietotemporal regions. To this end, four captive chimpanzees ( Pan
      troglodytes) were trained to reproduce 23 demonstrated actions, and four age-/sex
      matched controls were trained to produce basic husbandry behaviors in response to
      manual cues. Diffusion tensor images were acquired before and after 600 min of
      training over an average of 112 days. Bilateral and asymmetrical changes in
      frontoparietotemporal white matter integrity were compared between DAID trained
      subjects and controls. We found that imitation trained subjects exhibited
      leftward shifts in both mean fractional anisotropy and tract strength asymmetry
      measures in brain regions within the mirror system. This is the first report of
      training-induced changes in white matter integrity in chimpanzees and suggests
      that frontoparietotemporal connectivity, particularly in the left hemisphere, may
      have facilitated the emergence of increasingly complex imitation learning
      abilities.

PMID- 29211653
TI  - Exploring the Organization of Semantic Memory through Unsupervised Analysis of
      Event-related Potentials.
AB  - Modern multivariate methods have enabled the application of unsupervised
      techniques to analyze neurophysiological data without strict adherence to
      predefined experimental conditions. We demonstrate a multivariate method that
      leverages priming effects on the evoked potential to perform hierarchical
      clustering on a set of word stimuli. The current study focuses on the semantic
      relationships that play a key role in the organization of our mental lexicon of
      words and concepts. The N400 component of the event-related potential is
      considered a reliable neurophysiological response that is indicative of whether
      accessing one concept facilitates subsequent access to another (i.e., one
      "primes" the other). To further our understanding of the organization of the
      human mental lexicon, we propose to utilize the N400 component to drive a
      clustering algorithm that can uncover, given a set of words, which particular
      subsets of words show mutual priming. Such a scheme requires a reliable
      measurement of the amplitude of the N400 component without averaging across many
      trials, which was here achieved using a recently developed multivariate analysis
      method based on beamforming. We validated our method by demonstrating that it can
      reliably detect, without any prior information about the nature of the stimuli, a
      well-known feature of the organization of our semantic memory: the distinction
      between animate and inanimate concepts. These results motivate further
      application of our method to data-driven exploration of disputed or unknown
      relationships between stimuli.

PMID- 29211654
TI  - Does Extensive Training at Individuating Novel Objects in Adulthood Lead to
      Visual Expertise? The Role of Facelikeness.
AB  - Human adults have a rich visual experience thanks to seeing human faces since
      birth, which may contribute to the acquisition of perceptual processes that
      rapidly and automatically individuate faces. According to a generic visual
      expertise hypothesis, extensive experience with nonface objects may similarly
      lead to efficient processing of objects at the individual level. However, whether
      extensive training in adulthood leads to visual expertise remains debated. One
      key issue is the extent to which the acquisition of visual expertise depends on
      the resemblance of objects to faces in terms of the spatial configuration of
      parts. We therefore trained naive human adults to individuate a large set of
      novel parametric multipart objects. Critically, one group of participants trained
      with the objects in a "facelike" stimulus orientation, whereas a second group
      trained with the same objects but with the objects rotated 180 degrees  in the
      picture plane into a "nonfacelike" orientation. We used a fast periodic visual
      stimulation EEG protocol to objectively quantify participants' ability to
      discriminate untrained exemplars before and after training. EEG responses
      associated with the frequency of identity change in a fast stimulation sequence,
      which reflects rapid and automatic perceptual processes, were observed over
      lateral occipital sites for both groups before training. There was a significant,
      albeit small, increase in these responses after training but only for the
      facelike group and only to facelike stimuli. Our findings indicate that perceived
      facelikeness plays a role in visual expertise and highlight how the adult
      perceptual system exploits familiar spatial configurations when learning new
      object categories.

PMID- 29211655
TI  - Spectral Diversity in Default Mode Network Connectivity Reflects Behavioral
      State.
AB  - Default mode network (DMN) functional connectivity is thought to occur primarily
      in low frequencies (<0.1 Hz), resulting in most studies removing high frequencies
      during data preprocessing. In contrast, subtractive task analyses include high
      frequencies, as these are thought to be task relevant. An emerging line of
      research explores resting fMRI data at higher-frequency bands, examining the
      possibility that functional connectivity is a multiband phenomenon. Furthermore,
      recent studies suggest DMN involvement in cognitive processing; however, without
      a systematic investigation of DMN connectivity during tasks, its functional
      contribution to cognition cannot be fully understood. We bridged these concurrent
      lines of research by examining the contribution of high frequencies in the
      relationship between DMN and dorsal attention network at rest and during task
      execution. Our findings revealed that the inclusion of high frequencies alters
      between network connectivity, resulting in reduced anticorrelation and increased
      positive connectivity between DMN and dorsal attention network. Critically,
      increased positive connectivity was observed only during tasks, suggesting an
      important role for high-frequency fluctuations in functional integration.
      Moreover, within-DMN connectivity during task execution correlated with RT only
      when high frequencies were included. These results show that DMN does not simply
      deactivate during task execution and suggest active recruitment while performing
      cognitively demanding paradigms.

PMID- 29211656
TI  - The Neural Basis of Successful Word Reading in Aphasia.
AB  - Understanding the neural basis of recovery from stroke is a major research goal.
      Many functional neuroimaging studies have identified changes in brain activity in
      people with aphasia, but it is unclear whether these changes truly support
      successful performance or merely reflect increased task difficulty. We addressed
      this problem by examining differences in brain activity associated with correct
      and incorrect responses on an overt reading task. On the basis of previous
      proposals that semantic retrieval can assist pronunciation of written words, we
      hypothesized that recruitment of semantic areas would be greater on successful
      trials. Participants were 21 patients with left-hemisphere stroke with phonologic
      retrieval deficits. They read words aloud during an event-related fMRI paradigm.
      BOLD signals obtained during correct and incorrect trials were contrasted to
      highlight brain activity specific to successful trials. Successful word reading
      was associated with higher BOLD signal in the left angular gyrus. In contrast,
      BOLD signal in bilateral posterior inferior frontal cortex, SMA, and anterior
      cingulate cortex was greater on incorrect trials. These data show for the first
      time the brain regions where neural activity is correlated specifically with
      successful performance in people with aphasia. The angular gyrus is a key node in
      the semantic network, consistent with the hypothesis that additional recruitment
      of the semantic system contributes to successful word production when phonologic
      retrieval is impaired. Higher activity in other brain regions during incorrect
      trials likely reflects secondary engagement of attention, working memory, and
      error monitoring processes when phonologic retrieval is unsuccessful.

PMID- 29211657
TI  - Open-to-Air Is a Viable Option for Initial Wound Care in Necrotizing Soft Tissue
      Infection that Allows Early Detection of Recurrence without Need for Painful
      Dressing Changes or Return to Operating Room.
AB  - BACKGROUND: The standard treatment of necrotizing soft tissue infection (NSTI)
      includes extensive surgical debridement. Care of these debridements is
      challenging because of the size of the wound and associated pain. A potential
      solution is to leave the wounds open-to-air in the period after the initial
      debridement, allowing for regular inspection at bedside while reducing pain
      associated with frequent dressing changes. We evaluated the feasibility of this
      approach from a pain control standpoint. PATIENTS AND METHODS: An audit of wound
      care modalities used on adult patients with NSTI admitted to a regional burn
      center between January 2009 and May 2014 was performed. Patients with at least
      one operation were included. Those opting for palliative care were excluded.
      Wound care was divided into four categories: open-to-air (OTA), negative-pressure
      wound therapy (NPWT), packing, and ointment. Wound care, pain score, pain
      medication use, and number of operations were collected for the first seven days
      after initial debridement. Pain management was assessed by pain scores. Analgesic
      use was measured and compared using conversion to morphine milligram equivalents
      (MME). RESULTS: Ninety-six patients were included; 67% were men with average age
      of 50 years, resulting in a total of 672 days of wound care evaluated: 69 days of
      OTA, 127 days of NPWT, 200 days of packing, and 126 days of ointment (150 days
      were undocumented). Average daily pain score from all wound care modalities was
      2.00. Negative pressure wound therapy had the highest reported daily pain score
      (2.18, p = 0.034), whereas OTA had the lowest pain score (1.63, p < 0.05).
      Mortality was lower in the OTA cohort but was not statistically significant;
      there were no other differences in long-term outcome. CONCLUSION: Leaving wounds
      OTA is a safe and viable option in the immediate post-debridement period of NSTI
      to reduce pain, while permitting frequent re-evaluation for quick recognition of
      disease progression and repeat operative debridement if necessary.

PMID- 29211660
TI  - 2017 Subject Index.

PMID- 29211658
TI  - Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection remains a common complication after
      allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug
      that inhibits the CMV-terminase complex. METHODS: In this phase 3, double-blind
      trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of
      age or older, in a 2:1 ratio to receive letermovir or placebo, administered
      orally or intravenously, through week 14 after transplantation; randomization was
      stratified according to trial site and CMV disease risk. Letermovir was
      administered at a dose of 480 mg per day (or 240 mg per day in patients taking
      cyclosporine). Patients in whom clinically significant CMV infection (CMV disease
      or CMV viremia leading to preemptive treatment) developed discontinued the trial
      regimen and received anti-CMV treatment. The primary end point was the proportion
      of patients, among patients without detectable CMV DNA at randomization, who had
      clinically significant CMV infection through week 24 after transplantation.
      Patients who discontinued the trial or had missing end-point data at week 24 were
      imputed as having a primary end-point event. Patients were followed through week
      48 after transplantation. RESULTS: From June 2014 to March 2016, a total of 565
      patients underwent randomization and received letermovir or placebo beginning a
      median of 9 days after transplantation. Among 495 patients with undetectable CMV
      DNA at randomization, fewer patients in the letermovir group than in the placebo
      group had clinically significant CMV infection or were imputed as having a
      primary end-point event by week 24 after transplantation (122 of 325 patients
      [37.5%] vs. 103 of 170 [60.6%], P<0.001). The frequency and severity of adverse
      events were similar in the two groups overall. Vomiting was reported in 18.5% of
      the patients who received letermovir and in 13.5% of those who received placebo;
      edema in 14.5% and 9.4%, respectively; and atrial fibrillation or flutter in 4.6%
      and 1.0%, respectively. The rates of myelotoxic and nephrotoxic events were
      similar in the letermovir group and the placebo group. All-cause mortality at
      week 48 after transplantation was 20.9% among letermovir recipients and 25.5%
      among placebo recipients. CONCLUSIONS: Letermovir prophylaxis resulted in a
      significantly lower risk of clinically significant CMV infection than placebo.
      Adverse events with letermovir were mainly of low grade. (Funded by Merck;
      ClinicalTrials.gov number, NCT02137772 ; EudraCT number, 2013-003831-31 .).

PMID- 29211661
TI  - Evaluation of a Clinical Pharmacist-Led Multidisciplinary Antidepressant
      Telemonitoring Service in the Primary Care Setting.
AB  - Guidelines recommend patient follow-up within 2 weeks of antidepressant
      initiation or uptitration to minimize treatment discontinuation and suicidal
      ideation risks; however, time constraints and lack of systematic processes remain
      barriers in primary care. A pharmacist-led multidisciplinary telemonitoring
      service aimed to address these barriers. This was a retrospective, observational
      study of adults with depression initiated or uptitrated on an antidepressant
      between May and October 2016. Outcomes included the proportion of eligible
      patients successfully contacted, adherence, adverse effects, suicidal ideations,
      and pharmacist interventions. Clinical pharmacists successfully reached 258 of
      380 (68%) patients and provided follow-up in 298 calls. Patients endorsed
      antidepressant nonadherence during 56 (19%) calls, adverse effects in 81 (27%)
      calls, and suicidal ideations in 13 (4%) calls. Pharmacists provided 109 total
      interventions for 102 patients. The clinical pharmacist-led multidisciplinary
      antidepressant telemonitoring service is an alternative resource to monitor
      patients after antidepressant initiation or titration in primary care settings.

PMID- 29211662
TI  - Closing In on Treatment for Hemophilia B.

PMID- 29211663
TI  - Speed, Safety, and Industry Funding - From PDUFA I to PDUFA VI.

PMID- 29211664
TI  - Ecthyma Gangrenosum.

PMID- 29211665
TI  - Food Allergy.

PMID- 29211666
TI  - Oral Contraceptives and the Small Increased Risk of Breast Cancer.

PMID- 29211667
TI  - Pneumatosis Cystoides Intestinalis.

PMID- 29211668
TI  - Thrombophilia Testing and Venous Thrombosis.

PMID- 29211669
TI  - Use of Liver Imaging and Biopsy in Clinical Practice.

PMID- 29211670
TI  - Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia.

PMID- 29211672
TI  - Necrotizing Soft-Tissue Infections.

PMID- 29211673
TI  - Clinical Firsts - Christiaan Barnard's Heart Transplantations.

PMID- 29211674
TI  - Mechanisms of Resistance to Neoadjuvant Chemotherapy in Breast Cancer.

PMID- 29211675
TI  - An Unusual Cause of Leg Pain.

PMID- 29211676
TI  - Tiotropium in Early-Stage COPD.

PMID- 29211677
TI  - Medicaid Coverage for Family Planning - Can the Courts Stop the States from
      Excluding Planned Parenthood?

PMID- 29211679
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.
AB  - BACKGROUND: Little is known about whether contemporary hormonal contraception is
      associated with an increased risk of breast cancer. METHODS: We assessed
      associations between the use of hormonal contraception and the risk of invasive
      breast cancer in a nationwide prospective cohort study involving all women in
      Denmark between 15 and 49 years of age who had not had cancer or venous
      thromboembolism and who had not received treatment for infertility. Nationwide
      registries provided individually updated information about the use of hormonal
      contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among
      1.8 million women who were followed on average for 10.9 years (a total of 19.6
      million person-years), 11,517 cases of breast cancer occurred. As compared with
      women who had never used hormonal contraception, the relative risk of breast
      cancer among all current and recent users of hormonal contraception was 1.20 (95%
      confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI,
      0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with
      more than 10 years of use (P=0.002). After discontinuation of hormonal
      contraception, the risk of breast cancer was still higher among the women who had
      used hormonal contraceptives for 5 years or more than among women who had not
      used hormonal contraceptives. Risk estimates associated with current or recent
      use of various oral combination (estrogen-progestin) contraceptives varied
      between 1.0 and 1.6. Women who currently or recently used the progestin-only
      intrauterine system also had a higher risk of breast cancer than women who had
      never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33).
      The overall absolute increase in breast cancers diagnosed among current and
      recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000
      person-years, or approximately 1 extra breast cancer for every 7690 women using
      hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was
      higher among women who currently or recently used contemporary hormonal
      contraceptives than among women who had never used hormonal contraceptives, and
      this risk increased with longer durations of use; however, absolute increases in
      risk were small. (Funded by the Novo Nordisk Foundation.).

PMID- 29211680
TI  - The impact of water on the ambivalent behavior and paradoxical phenomenon of the
      amyloid-beta fibril protein.
AB  - The crucial role of water in amyloid-beta(Abeta) fibril proteins is evaluated in
      several ways including the water's thermodynamic and kinetic solvation effects.
      As regards the water's character, its hindered-rotation barriers are also
      considered. The following protein molecules considered here are: the Abeta40 (PDB
      ID: 2LMN), Abeta42 (PDB ID: 5KK3 and 2NAO) and the double-layered Abeta17-42
      fibril. We discuss: (i) extracellular Abeta40 and Abeta42 fibril monomers exhibit
      an ambivalent propensity to transform into a helical form toward the N-term
      region and a beta-strand-like form near the C-terminal; (ii) interfacial water
      molecules play a crucial role in protein-protein interactions, as molecular
      dynamics simulations have shown a significant impact on the protein-protein
      binding; (iii) it is shown that the spontaneous dimerization process of the
      Abeta42 fibril protein in water occurs via a two-step nucleation-accommodation
      mechanism; (iv) MD simulations of the double-layered Abeta17-42 fibril model show
      that the C<->C interface appears more energetically favorable than the N<->N
      interface due to large hydrophobic contacts; (v) the water's role in the HET-s
      prion and in the Abeta fibrillar aggregates; (vi) it was found that the monomer
      oligomer equilibrium spontaneously dissociates into stable monomeric species when
      they are incubated up to 3 MUm for a longer time (>1 week) in a physiological
      buffer.

PMID- 29211678
TI  - Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant.
AB  - BACKGROUND: The prevention of bleeding with adequately sustained levels of
      clotting factor, after a single therapeutic intervention and without the need for
      further medical intervention, represents an important goal in the treatment of
      hemophilia. METHODS: We infused a single-stranded adeno-associated viral (AAV)
      vector consisting of a bioengineered capsid, liver-specific promoter and factor
      IX Padua (factor IX-R338L) transgene at a dose of 5*1011 vector genomes per
      kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant
      activity of 2% or less of the normal value. Laboratory values, bleeding
      frequency, and consumption of factor IX concentrate were prospectively evaluated
      after vector infusion and were compared with baseline values. RESULTS: No serious
      adverse events occurred during or after vector infusion. Vector-derived factor IX
      coagulant activity was sustained in all the participants, with a mean (+/-SD)
      steady-state factor IX coagulant activity of 33.7+/-18.5% (range, 14 to 81). On
      cumulative follow-up of 492 weeks among all the participants (range of follow-up
      in individual participants, 28 to 78 weeks), the annualized bleeding rate was
      significantly reduced (mean rate, 11.1 events per year [range, 0 to 48] before
      vector administration vs. 0.4 events per year [range, 0 to 4] after
      administration; P=0.02), as was factor use (mean dose, 2908 IU per kilogram
      [range, 0 to 8090] before vector administration vs. 49.3 IU per kilogram [range,
      0 to 376] after administration; P=0.004). A total of 8 of 10 participants did not
      use factor, and 9 of 10 did not have bleeds after vector administration. An
      asymptomatic increase in liver-enzyme levels developed in 2 participants and
      resolved with short-term prednisone treatment. One participant, who had
      substantial, advanced arthropathy at baseline, administered factor for bleeding
      but overall used 91% less factor than before vector infusion. CONCLUSIONS: We
      found sustained therapeutic expression of factor IX coagulant activity after gene
      transfer in 10 participants with hemophilia who received the same vector dose.
      Transgene-derived factor IX coagulant activity enabled the termination of
      baseline prophylaxis and the near elimination of bleeding and factor use. (Funded
      by Spark Therapeutics and Pfizer; ClinicalTrials.gov number, NCT02484092 .).

PMID- 29211681
TI  - Effect of mindfulness meditation on short-term weight loss and eating behaviors
      in overweight and obese adults: A randomized controlled trial.
AB  - Background There is a significant health crisis with rates of obesity continuing
      to increase despite research and clinical standard behavioral weight loss
      programs (SBWP). Mindfulness meditation (MM), with demonstrated benefits on
      physical, psychological health, and self-regulation behaviors was explored with
      SBWP. Methods Forty-six adults (BMI=32.5+/-3.7 kg/m2; age=45.2+/-8.2 years, 87 %
      female, 21.7 % African American) were randomly assigned to a 6-month SBWP only
      (n=24) or SBWP+MM (n=22) at a university-based physical activity and weight
      management research center in a northeastern US city. Participants were
      instructed to decrease intake (1200-1500 kcal/day), increase physical activity
      (300 min/wk), and attend weekly SBWP or SBWP+MM sessions. SBWP+MM had the same
      SBWP lessons with addition of focused MM training. Outcome measures collected at
      0, 3, and 6 months included: weight, Block Food Frequency Questionnaire, Eating
      Behavior Inventory, Eating Inventory and Paffenbarger Physical Activity
      Questionnaire. Data were analyzed using linear mixed modeling for efficacy
      analysis of weight (primary) and eating, exercise and mindfulness (secondary
      outcomes). Results Retention rate was 76.1 % (n=35). A significant group by time
      interaction (p=0.03) was found for weight, with weight loss favoring SBWP+MM (
      6.9 kg+2.9) over SBWP (-4.1 kg+2.8). Eating behaviors (p=0.02) and dietary
      restraint (p=0.02) improved significantly in SBWP+MM, compared to SBWP. MM
      enhanced weight loss by 2.8 kg potentially through greater improvements in eating
      behaviors and dietary restraint. Conclusions These findings support further study
      into the use of MM strategies with overweight and obese adults. The use of this
      low-cost, portable strategy with standard behavioral interventions could improve
      weight management outcomes.

PMID- 29211682
TI  - The natural history of subependymal giant cell astrocytomas in tuberous sclerosis
      complex: a review.
AB  - Tuberous sclerosis complex (TSC) is an auto-somal-dominant inherited condition
      with an incidence of approximately 1:6000 births, characterised by deregulated
      mTOR activity with multi-site hamartomas. Subependymal giant cell astrocytomas
      (SEGA) are one such hamartoma, affecting up to 24% of patients with TSC. Their
      intraventricular location may lead to life-threatening obstructive hydrocephalus.
      Current management is hampered by a lack of understanding regarding the natural
      history, behaviour and growth patterns of SEGA. We review the current literature
      to summarise what is known about SEGA in the following areas: (1) diagnostic
      criteria, (2) prevalence, (3) origin, (4) imaging characteristics, (5) growth
      rate, (6) genotype-phenotype correlation, (7) congenital SEGA and (8) SEGA as a
      marker of severity of other TSC manifestations.

PMID- 29211683
TI  - Understanding the controversial drug targets in epilepsy and pharmacoresistant
      epilepsy.
AB  - Accumulating experimental data suggests a number of successful drug targets
      against epilepsy which eventually failed in the clinical setup. Mammalian target
      of rapamycin inhibitors, multi-drug resistance transporter inhibitors, cyclo
      oxygenase-2 inhibitors, statins, etc. are the most promising and well studied
      among them. Drugs aiming at these targets produced beneficial response in most of
      the in vitro and in vivo seizure models. However, in certain situations, they
      have produced differential rather controversial results. Their effects varied
      with the seizure model, species, time and route of administration, different
      drugs from the same class, etc. This review emphasises on such drugs which
      presented with variability in their beneficial effects against seizures and
      epilepsy. This review critically summarises the preclinical evidence of these
      targets in the context of seizures and the probable reasons for their variability
      and clinical failures.

PMID- 29211684
TI  - Independent component analysis for cochlear implant artifacts attenuation from
      electrically evoked auditory steady-state response measurements.
AB  - OBJECTIVE: Electrically evoked auditory steady-state responses (EASSRs) are
      potentially useful for objective cochlear implant (CI) fitting and follow-up of
      the auditory maturation in infants and children with a CI. EASSRs are recorded in
      the electro-encephalogram (EEG) in response to electrical stimulation with
      continuous pulse trains, and are distorted by significant CI artifacts related to
      this electrical stimulation. The aim of this study is to evaluate a CI artifacts
      attenuation method based on independent component analysis (ICA) for three EASSR
      datasets. APPROACH: ICA has often been used to remove CI artifacts from the EEG
      to record transient auditory responses, such as cortical evoked auditory
      potentials. Independent components (ICs) corresponding to CI artifacts are then
      often manually identified. In this study, an ICA based CI artifacts attenuation
      method was developed and evaluated for EASSR measurements with varying CI
      artifacts and EASSR characteristics. Artifactual ICs were automatically
      identified based on their spectrum. MAIN RESULTS: For 40 Hz amplitude modulation
      (AM) stimulation at comfort level, in high SNR recordings, ICA succeeded in
      removing CI artifacts from all recording channels, without distorting the EASSR.
      For lower SNR recordings, with 40 Hz AM stimulation at lower levels, or 90 Hz AM
      stimulation, ICA either distorted the EASSR or could not remove all CI artifacts
      in most subjects, except for two of the seven subjects tested with low level 40
      Hz AM stimulation. Noise levels were reduced after ICA was applied, and up to 29
      ICs were rejected, suggesting poor ICA separation quality. SIGNIFICANCE: We
      hypothesize that ICA is capable of separating CI artifacts and EASSR in case the
      contralateral hemisphere is EASSR dominated. For small EASSRs or large CI
      artifact amplitudes, ICA separation quality is insufficient to ensure complete CI
      artifacts attenuation without EASSR distortion.

PMID- 29211685
TI  - Optimisation of sampling parameters for standardised exhaled breath sampling.
AB  - The lack of standardisation of breath sampling is a major contributing factor to
      the poor repeatability of results and hence represents a barrier to the adoption
      of breath tests in clinical practice. On-line and bag breath sampling have
      advantages but do not suit multicentre clinical studies whereas storage and
      robust transport are essential for the conduct of wide-scale studies. Several
      devices have been developed to control sampling parameters and to concentrate
      volatile organic compounds (VOCs) onto thermal desorption (TD) tubes and
      subsequently transport those tubes for laboratory analysis. We conducted three
      experiments to investigate (i) the fraction of breath sampled (whole versus lower
      expiratory exhaled breath); (ii) breath sample volume (125, 250, 500 and 1000
      ml); and (iii) breath sample flow rate (400, 200, 100 and 50 ml min-1). The
      target VOCs were acetone and potential volatile biomarkers for oesophago-gastric
      cancer belonging to the aldehyde, fatty acids and phenol chemical classes. We
      also examined the collection execution time and the impact of environmental
      contamination. The experiments showed that the use of exhaled breath-sampling
      devices requires the selection of optimum sampling parameters. The increase in
      sample volume has improved the levels of VOCs detected. However, the influence of
      the fraction of exhaled breath and the flow rate depends on the target VOCs
      measured. The concentration of potential volatile biomarkers for oesophago
      gastric cancer was not significantly different between the whole and lower airway
      exhaled breath. While the recovery of phenols and acetone from TD tubes was lower
      when breath sampling was performed at a higher flow rate, other VOCs were not
      affected. A dedicated 'clean air supply' reduces the contamination from ambient
      air, but the breath collection device itself can be a source of contaminants. In
      clinical studies using VOCs to elicit potential biomarkers of gastro-oesophageal
      cancer, the optimum parameters are 500 mls sample volume of whole breath with a
      flow rate of 200 ml min-1.

PMID- 29211686
TI  - Integration of risks from multiple hazards into a holistic ALARA/ALARP
      demonstration.
AB  - The principle of As Low As Reasonable Achievable (ALARA) stems from the field of
      radiological protection. In the UK, this principle has been incorporated into the
      Health and Safety at Work Act 1974 and rather than applying solely to
      radiological hazards, applies to all hazards in totality. Given that the current
      methods for assessing hazards are somewhat isolated, in that one hazard is
      assessed independently of another, it can be challenging to ensure a truly
      holistic view of the risks, and demonstrate they have been reduced to ALARA or As
      Low As Is Reasonably Practicable (ALARP) as required in the UK regulatory regime.
      The following paper presents a proposed framework for the integrated assessment
      of risks from multiple hazards. In addition, it presents an overview of some of
      the key challenges that may be encountered when producing a holistic ALARA
      demonstration.

PMID- 29211687
TI  - Cellular reprogramming dynamics follow a simple 1D reaction coordinate.
AB  - Cellular reprogramming, the conversion of one cell type to another, induces
      global changes in gene expression involving thousands of genes, and understanding
      how cells globally alter their gene expression profile during reprogramming is an
      ongoing problem. Here we reanalyze time-course data on cellular reprogramming
      from differentiated cell types to induced pluripotent stem cells (iPSCs) and show
      that gene expression dynamics during reprogramming follow a simple 1D reaction
      coordinate. This reaction coordinate is independent of both the time it takes to
      reach the iPSC state as well as the details of the experimental protocol used.
      Using Monte-Carlo simulations, we show that such a reaction coordinate emerges
      from epigenetic landscape models where cellular reprogramming is viewed as a
      'barrier-crossing' process between cell fates. Overall, our analysis and model
      suggest that gene expression dynamics during reprogramming follow a canonical
      trajectory consistent with the idea of an 'optimal path' in gene expression space
      for reprogramming.

PMID- 29211688
TI  - Possible half-metallicity and variable range hopping transport in Sb-substituted
      Fe2TiSn Heusler alloys.
AB  - The investigation of the magnetotransport properties on [Formula: see text]
      [Formula: see text]Sb x with 0 [Formula: see text] 0.6 are presented in this
      paper. The substitution of Sb in place of Sn decreases the anti-site disorder as
      evident from x-ray diffraction patterns as well as from transport properties
      measurement. The much-disputed upturn in low temperature electrical resistivity
      of [Formula: see text]TiSn has been demonstrated to be a result of weak
      localization induced by anti-site disorder. With increased Sb substitution (?25%)
      the metallic transport behavior of [Formula: see text]TiSn changes to
      semiconductor-like. At low temperature, carrier transport in such compositions
      occurs via the variable range hopping mechanism. Moreover, a systematic increase
      in the anomalous Hall voltage is observed with increasing Sb-content,
      attributable to a side jump or Berry phase curvature effect. Electrical
      resistivity in the entire temperature regime hints towards half metallicity of
      the system. Our ab initio electronic structure calculations using generalised
      gradient approximation formalism further supports the results of our
      magnetotransport study.

PMID- 29211689
TI  - Balancing strength, hardness and ductility of Cu64Zr36 nanoglasses via embedded
      nanocrystals.
AB  - Superplasticity can be achieved in nanoglasses but at the expense of strength,
      and such a loss can be mitigated via embedding stronger nanocrystals, i.e.,
      forming nanoglass/nanocrystal composites. As an illustrative case, we investigate
      plastic deformation of Cu64Zr36 nanoglass/nanocrystalline Cu composites during
      uniaxial tension and nanoindentation tests with molecular dynamics simulations.
      With an increasing fraction of nanocrystalline grains, the tensile strength of
      the composite is enhanced, while its ductility decreases. The dominant interface
      type changes from a glass-glass interface to glass-crystal interface to grain
      boundary, corresponding to a failure mode transition from superplastic flow to
      shear banding to brittle intercrystal fracture, respectively. Accordingly, the
      indentation hardness increases continuously and strain localization beneath the
      indenter is more and more severe. For an appropriate fraction of nanocrystalline
      grains, a good balance among strength, hardness and ductility can be realized,
      which is useful for the synthesis of novel nanograined glass/crystalline
      composites with high strength, high hardness and superior ductility.

PMID- 29211690
TI  - Assessment of a combined gas chromatography mass spectrometer sensor system for
      detecting biologically relevant volatile compounds.
AB  - There have been a number of studies in which metal oxide sensors (MOS) have
      replaced conventional analytical detectors in gas chromatography systems.
      However, despite the use of these instruments in a range of applications
      including breath research the sensor responses (i.e. resistance changes w.r.t.
      concentration of VCs) remain largely unreported. This paper addresses that issue
      by comparing the response of a metal oxide sensor directly with a mass
      spectrometer (MS), whereby both detectors are interfaced to the same GC column
      using an s-swafer. It was demonstrated that the sensitivity of an in-house
      fabricated ZnO/SnO2 thick film MOS was superior to a modern MS for the detection
      of a wide range of volatile compounds (VCs) of different functionalities and
      masses. Better techniques for detection and quantification of these VCs is
      valuable, as many of these compounds are commonly reported throughout the
      scientific literature. This is also the first published report of a combined GC
      MS sensor system. These two different detector technologies when combined, should
      enhance discriminatory abilities to aid disease diagnoses using volatiles from
      e.g. breath, and bodily fluids. Twenty-nine chemical standards have been tested
      using solid phase micro-extraction; 25 of these compounds are found on human
      breath. In all but two instances the sensor exhibited the same or superior limit
      of detection compared to the MS. Twelve stool samples from healthy participants
      were analysed; the sensor detected, on average 1.6 peaks more per sample than the
      MS. Similarly, analysing the headspace of E. coli broth cultures the sensor
      detected 6.9 more peaks per sample versus the MS. This greater sensitivity is
      primarily a function of the superior limits of detection of the metal oxide
      sensor. This shows that systems based on the combination of chromatography
      systems with solid state sensors shows promise for a range of applications.

PMID- 29211691
TI  - Long-term monitoring of water treatment technology designed for radium removal
      removal efficiencies and NORM formation.
AB  - A drinking water treatment plant in Viimsi, Estonia, was monitored over three
      years for iron, manganese, radium-226, radium-228, as well as their daughter
      nuclides, in order to determine the efficiency of the treatment process, gain an
      insight into the removal mechanisms and interactions between radium, iron, and
      manganese, and assess the overall longevity and performance of the technology
      along with the possible build-up of NORM in the treatment process. During the
      study, samples were collected from raw water, first and second stage filtrate,
      consumer water, backwash water and filter materials. The results show consistent
      removal efficiency for iron and manganese, as well as an average of over 85%
      removal for radium with a slight decline over time. The backwash process has been
      optimised for maximum radium removal from the filters, while keeping
      concentrations in the backwash water below exemption levels. However, the
      accumulation of radium and thorium occurs in the filter material, exceeding
      exemption levels in the top layer of the filter columns in less than a year. By
      the end of the observation period, activity concentrations in the top layer of
      the columns were above 30 000 Bq kg-1 for Ra-226 and Ra-228, and around 15 000 Bq
      kg-1 for Th-228. Radionuclides are not homogenously distributed in the filter
      columns. In order to estimate the average activity concentrations in the filter
      media, the height distribution of radionuclides has to be accounted for. Two
      years and two months after commissioning the treatment plant, the average
      activity concentrations of Ra isotopes in the filter columns were in the range 10
      000 Bq kg-1, while Th-228 activity concentration was roughly 3500 Bq kg-1.

PMID- 29211692
TI  - A Molecular and Cytogenetic Update on Non-Small Cell Lung Carcinoma.
AB  - Lung cancer is one of the leading causes of cancer-related death worldwide. Among
      patients with lung cancer, approximately 85% have non-small cell lung carcinoma
      (NSCLC). The discovery of oncogenic driver mutations in NSCLC opened new
      personalized treatment options. Several methods that can identify these
      biomarkers are used routinely in a clinical setting to stratify patients for
      targeted therapy. In this review, we summarize the most clinically relevant
      driver genes, discuss the advantages and limitations of current clinical
      detection methods, and highlight the benefits of personalized treatment over
      standard chemotherapy.

PMID- 29211693
TI  - The t(12;21)(p13;q22) in Pediatric B-Acute Lymphoblastic Leukemia: An Update.
AB  - Erratum: Figure 1 on the last edition The Journal of the Association of Genetic
      Technologists. 2017;43(3): 113-127 does not contain the derivative 21. We are
      replacing this figure with the present one. In the section Secondary genetic
      aberrations we would like to add that: Deletions of 11q23 are observed in 5-6% of
      cases (Raynaud et al., 1999; Attarbaschi et al., 2004; Alvarez et al., 2005;
      Forestier et al., 2007).

PMID- 29211671
TI  - Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.
AB  - BACKGROUND: The post-thrombotic syndrome frequently develops in patients with
      proximal deep-vein thrombosis despite treatment with anticoagulant therapy.
      Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical
      thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of
      the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with
      acute proximal deep-vein thrombosis to receive either anticoagulation alone
      (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter
      mediated or device-mediated intrathrombus delivery of recombinant tissue
      plasminogen activator and thrombus aspiration or maceration, with or without
      stenting). The primary outcome was development of the post-thrombotic syndrome
      between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was
      no significant between-group difference in the percentage of patients with the
      post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and
      48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to
      1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events
      within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant
      difference in recurrent venous thromboembolism was seen over the 24-month follow
      up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control
      group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of
      patients in the pharmacomechanical-thrombolysis group versus 24% of those in the
      control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores
      for the post-thrombotic syndrome were lower in the pharmacomechanical
      thrombolysis group than in the control group at 6, 12, 18, and 24 months of
      follow-up (P<0.01 for the comparison of the Villalta scores at each time point),
      but the improvement in quality of life from baseline to 24 months did not differ
      significantly between the treatment groups. CONCLUSIONS: Among patients with
      acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter
      directed thrombolysis to anticoagulation did not result in a lower risk of the
      post-thrombotic syndrome but did result in a higher risk of major bleeding.
      (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT
      ClinicalTrials.gov number, NCT00790335 .).

PMID- 29211695
TI  - Minimally invasive brow lifting techniques: erratum.

PMID- 29211696
TI  - Green neutrophilic inclusions: current understanding and review of literature.
AB  - PURPOSE OF REVIEW: Green cytoplasmic inclusions in neutrophils are an uncommon
      finding on the peripheral blood smear. A comprehensive review of the literature
      is presented here with the goal of summarizing knowledge to date and increasing
      awareness. RECENT FINDINGS: A total of 41 cases have been reported in the
      literature, indicating the rarity of these green neutrophilic inclusions.
      Clinically, the inclusions have most consistently been associated with elevated
      transaminases, hepatic failure, and a high early mortality rate. The precise
      composition of the inclusions has not been confirmed. SUMMARY: Clinicians,
      hematologists, and laboratory technicians should be educated and have a high
      level of awareness of green neutrophilic inclusions. A more comprehensive
      analysis of a larger number of cases will be needed to clarify the true
      prevalence, associated conditions, biochemical nature, and clinical significance
      of this unusual finding.

PMID- 29211694
TI  - Prevention of bladder cancer incidence and recurrence: nutrition and lifestyle.
AB  - PURPOSE OF REVIEW: We review the influence of nutrition and lifestyle on bladder
      cancer incidence and recurrence and summarize food items, diets and lifestyle
      practices that physicians may wish to prioritize for discussion with their
      patients. RECENT FINDINGS: Recent study results suggest an association between
      bladder cancer incidence and several food items including meat, fruit,
      vegetables, milk products and oil. Micronutrient deficiency is associated with
      bladder cancer risk; however, it remains unclear if micronutrient supplementation
      can modify bladder cancer incidence. Furthermore, total fluid intake, alcohol,
      coffee and tea seem to have no influence on bladder cancer incidence. There is
      weak evidence that stress, anxiety and lack of sleep may increase the risk of
      developing bladder cancer, whereas exercise may reduce the risk of dying from it.
      SUMMARY: Several dietary items and life styles are associated with bladder cancer
      incidence and recurrence. However, besides smoking cessation, there is no
      evidence that a certain diet or lifestyle can decrease bladder cancer incidence.

PMID- 29211697
TI  - Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil
      mediated autoimmunity.
AB  - PURPOSE OF REVIEW: Levamisole was previously used for its immunomodulatory
      properties to treat rheumatoid arthritis and some cancers. However, because of
      serious side-effects, it was taken off the market in the United States. Recently,
      levamisole has reemerged as a popular cocaine adulterant. Some individuals who
      consume levamisole-adulterated cocaine can develop a life-threatening autoimmune
      syndrome. In this review, the medical consequences of levamisole exposure and
      postulated mechanisms by which levamisole induces these adverse effects are
      discussed. RECENT FINDINGS: Although agranulocytosis and cutaneous vasculitis are
      the major findings in patients who develop cocaine/levamisole-associated
      autoimmune syndrome (CLAAS), more recent experience indicates that other organ
      systems can be involved as well. Current studies point to neutrophil activation
      and neutrophil extracellular trap formation with subsequent antineutrophil
      cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS.
      SUMMARY: In the past decade, the detrimental effects of levamisole have reemerged
      because of its popularity as a cocaine adulterant. Although infrequent, some
      individuals develop a systemic autoimmune syndrome characterized by immune
      mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated
      vasculitis. Mechanistically, neutrophil antigens appear to be a major player in
      inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment,
      although relapses are frequent because of the addictive effects of cocaine and
      the high prevalence of levamisole within the cocaine supply.

PMID- 29211698
TI  - Branched-chain amino acid metabolism in cancer.
AB  - PURPOSE OF REVIEW: The current review aims to provide an update on the recent
      biomedical interest in oncogenic branched-chain amino acid (BCAA) metabolism, and
      discusses the advantages of using BCAAs and expression of BCAA-related enzymes in
      the treatment and diagnosis of cancers. RECENT FINDINGS: An accumulating body of
      evidence demonstrates that BCAAs are essential nutrients for cancer growth and
      are used by tumors in various biosynthetic pathways and as a source of energy. In
      addition, BCAA metabolic enzymes, such as the cytosolic branched-chain
      aminotransferase 1 (BCAT1) and mitochondrial branched-chain aminotransferase 2,
      have emerged as useful prognostic cancer markers. BCAT1 expression commonly
      correlates with more aggressive cancer growth and progression, and has attracted
      substantial scientific attention in the past few years. These studies have found
      the consequences of BCAT1 disruption to be heterogeneous; not all cancers share
      the same requirements for BCAA metabolites and the function of BCAT1 appears to
      vary between cancer types. SUMMARY: Both oncogenic mutations and cancer tissue-of
      origin influence BCAA metabolism and expression of BCAA-associated metabolic
      enzymes. These new discoveries need to be taken into consideration during the
      development of new cancer therapies that target BCAA metabolism.

PMID- 29211699
TI  - Robotic Versus Laparoscopic Gastrectomy for Locally Advanced Gastric Cancer.
AB  - Robotic gastrectomy (RG) has progressed rapidly in the last decade, overcoming
      many obstacles in laparoscopic technology. We compared surgical performance and
      short-term clinical outcomes between RG and laparoscopic gastrectomy (LG). In
      total, 163 patients with gastric cancer were randomly treated with RG (n=102) or
      LG (n=61). D2 lymphadenectomy was achieved in all patients. Digestive tract
      reconstruction in the RG group was performed by intracorporeal hand sewing, but
      extracorporeal anastomosis in the LG group was performed with a 25-mm circular
      stapler or linear stapler. Compared with the LG group, the RG group had less
      intraoperative blood loss (P=0.005) and more lymph nodes retrieved (P=0.000).
      Postoperative complications between the 2 groups were not significantly different
      during the 11-month follow-up (P=0.063). Compared with LG, RG is a feasible and
      safe approach with minimally invasive, satisfactory intracorporeal digestive
      tract reconstruction, and fast recovery. Multicenter randomized controlled
      studies of larger numbers of patients are needed.

PMID- 29211700
TI  - Effect of Histocompatibility Y Antigen Matching on Graft Survival in Primary
      Penetrating Keratoplasty.
AB  - PURPOSE: To investigate the influence of histocompatibility Y (H-Y) antigen
      matching on corneal graft survival in primary penetrating keratoplasty (PK).
      METHODS: Medical records of patients who underwent primary PK at Seoul National
      University Bundang Hospital between June 2005 and October 2015 were
      retrospectively analyzed. The eyes were classified into 2 groups: H-Y-compatible
      (115 eyes) and H-Y-incompatible (23 eyes). The H-Y-compatible group included
      donor/recipient combinations of male/male (57 eyes), female/male (44 eyes), and
      female/female (14 eyes). The H-Y-incompatible group included the male/female (23
      eyes) combination alone. A subgroup analysis of low- and high-risk patients
      according to preoperative diagnoses was also performed. Survival analysis was
      conducted using the Kaplan-Meier method; differences between groups were assessed
      with a log-rank test. RESULTS: A total of 138 eyes from 136 patients (age: 58 +/-
      18 years) were enrolled. Rejection-free graft survival and graft survival were
      not significantly different between H-Y-compatible and H-Y-incompatible groups
      (chi = 0.4, P = 0.548; chi = 1.9; P = 0.17, respectively). Preoperative diagnoses
      of high-risk cases included those with corneal perforation or thinning (8.7%) and
      infectious keratitis (7.2%). Low-risk cases included corneal opacity (50.0%),
      bullous keratopathy (25.4%), keratoconus (5.8%), and corneal dystrophy (2.9%). In
      the high-risk group, rejection-free graft survival rate was significantly higher
      in the H-Y-compatible group (chi = 3.9, P = 0.049). CONCLUSIONS: H-Y antigen
      matching does not influence graft rejection and failure in cases of primary PK.
      However, matching the H-Y antigen could help reduce graft rejection, especially
      in preoperatively high-risk patients.

PMID- 29211701
TI  - New Grading System for Limbal Dermoid: A Retrospective Analysis of 261 Cases Over
      a 10-Year Period.
AB  - PURPOSE: To establish a new scoring system for limbal dermoid, in order to unify
      the diagnostic criteria and assess the prognosis. METHODS: A retrospective study
      was conducted on 261 patients with limbal dermoid. The basic information,
      clinical features, and pathology of dermoids were recorded, and the prognosis at
      1 year after keratoplasty was assessed at follow-up. A new visual scoring system
      was created for the area of corneal involvement, the area of conjunctival
      involvement, and the surface shape. RESULTS: There were 154 females and 107 males
      with mean age of 4 +/- 3 years at surgery. After scoring, 59% (136) of patients
      were classified as grade I, 26% (60) as grade II, and 14% (33) as grade III. The
      pathological results were 124 dermoid cases, 76 lipodermoid, 5 complex
      choristoma, and 10 epibulbar osseous choristoma. Moreover, patients with lower
      clinical scores presented a better prognosis; the mean logarithm of the minimum
      angle of resolution (logMAR) best-corrected visual acuity in grade I patients was
      0.38 +/- 0.05, which was better than the grade II value of 0.61 +/- 0.09 (P <
      0.05) and the grade III value of 0.94 +/- 0.11 (P < 0.001). CONCLUSIONS: New
      grading systems for limbal dermoid were useful for clinical diagnosis and may
      have prognostic value in predicting visual acuity. A lower-grade dermoid
      exhibited better vision postoperatively.

PMID- 29211703
TI  - Intra-articular findings during the modified Brostrom procedure for lateral
      instability of the pediatric ankle.
AB  - : The purpose of this study was to identify the rates of chondral injury, soft
      tissue impingement, and bony impingement in pediatric patients undergoing the
      modified Brostrom procedure with ankle arthroscopy for lateral ankle instability.
      A retrospective review of all patients undergoing a modified Brostrom procedure
      with ankle arthroscopy performed by two surgeons at a tertiary care children's
      hospital between October 2002 and April 2014 was performed. Data were collected
      regarding demographics, history and initial presentation, nonoperative
      management, surgical procedure and arthroscopic findings, and clinical follow-up.
      All patients had symptoms of ankle instability and had failed nonoperative
      management before surgery. A total of 69 patients were reviewed (75 ankles), of
      whom 54 (78%) were female and six underwent bilateral surgery. The mean+/-SD age
      was 15.2+/-2.6 years, and the mean BMI was 23.6+/-5.0 kg/m. All patients had
      preoperative radiography and MRI. Preoperative imaging within 1 year before
      surgery was available for review of 57 (76%) ankles, with 16 (28%) having open
      physes, 28 (49%) having closing physes, and 13 (23%) having closed physes. All
      patients reviewed underwent the Brostrom procedure with Gould modification and
      routine concurrent arthroscopy. During arthroscopy, anterior soft tissue
      impingement was noted in 49 (65%) ankles, synovitis in 40 (53%), chondral defect
      in eight (11%), loose body in three (4%), and none were found to have bony
      impingement. Soft tissue impingement (65%) is common in pediatric patients
      undergoing surgery for lateral ankle instability. Bony impingement (0%) and
      chondral injury (11%) are uncommon. This is in contrast to the adult population
      where bony impingement and chondral injury are more common. LEVEL OF EVIDENCE:
      Level IV Case Series.

PMID- 29211704
TI  - Histone Deacetylase (HDAC) Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA),
      Induces Apoptosis in Prostate Cancer Cell Lines via the Akt/FOXO3a Signaling
      Pathway.
AB  - BACKGROUND Histone deacetylase (HDAC) inhibitors are emerging as a new class of
      anti-cancer drugs that promote cancer cell apoptosis, and include suberoylanilide
      hydroxamic acid (SAHA). The aim of this study was to investigate the mechanism of
      SAHA-induced apoptosis in human prostate cancer cell lines, DU145 and PC-3.
      MATERIAL AND METHODS Cell lines, DU145 and PC-3, were studied before and after
      treatment with SAHA. The effects of SAHA treatment on cell proliferation were
      studied using the MTT cell proliferation assay. Annexin-V-fluorescein
      isothiocyanate (FITC) and propidium iodide (PI) staining were used to study the
      effects of SAHA treatment on cell apoptosis. Western blotting, quantitative
      polymerase chain reaction (qPCR) and short interfering (si)RNA assays were
      performed to study the effects of SAHA treatment on apoptotic and cell cycle
      proteins and the Akt/FOXO3a signaling pathway. RESULTS Treatment with SAHA
      inhibited cell proliferation in human prostate cancer cell lines DU145 and PC-3
      cells in a dose-dependent way. Cell cycle analysis and Annexin-V FITC/PI staining
      showed that treatment with SAHA resulted in G2/M cell cycle arrest and increased
      cell apoptosis in a dose-dependent way. Also, treatment with SAHA reduced the
      protein expression levels cyclin B and cyclin A2 and promoted the activation of
      FOXO3a by inhibiting Akt activation. Western blotting, the siRNA assay, and qPCR
      showed that FOXO3a, the Bcl-2 family of proteins, survivin, and FasL were
      involved in SAHA-induced apoptosis in prostate cancer cells grown in vitro.
      CONCLUSIONS Treatment with SAHA promoted apoptosis via the Akt/FOXO3a signaling
      pathway in prostate cancer cells in vitro.

PMID- 29211705
TI  - A workshop on 'Dietary Sweetness-Is It an Issue?'
AB  - This report summarises a workshop convened by ILSI Europe on 3 and 4 April 2017
      to discuss the issue of dietary sweetness. The objectives were to understand the
      roles of sweetness in the diet, establish whether exposure to sweetness affects
      diet quality and energy intake, and consider whether sweetness per se affects
      health. Although there may be evidence for tracking of intake of some sweet
      components of the diet through childhood, evidence for tracking of whole diet
      sweetness, or through other stages of maturity are lacking. The evidence to date
      does not support adverse effects of sweetness on diet quality or energy intake,
      except where sweet food choices increase intake of free sugars. There is some
      evidence for improvements in diet quality and reduced energy intake where
      sweetness without calories replaces sweetness with calories. There is a need to
      understand the physiological and metabolic relevance of sweet taste receptors on
      the tongue, in the gut and elsewhere in the body, as well as possible
      differentiation in the effects of sustained consumption of individual sweeteners.
      Despite a plethora of studies, there is no consistent evidence for an association
      of sweetness sensitivity/preference with obesity or type 2 diabetes. A
      multifaceted integrated approach, characterising nutritive and sensory aspects of
      the whole diet or dietary patterns, may be more valuable in providing contextual
      insight. The outcomes of the workshop could be used as a scientific basis to
      inform the expert community and create more useful dialogue among health care
      professionals.

PMID- 29211706
TI  - Response to 'Jangle fallacy epidemic in obesity research: a comment on Ruddock et
      al. (2017)'.

PMID- 29211707
TI  - Obesity and obesogenic growth are both highly heritable and modified by diet in a
      nonhuman primate model, the African green monkey (Chlorocebus aethiops sabaeus).
AB  - OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the
      genetics underlying it has been historically difficult to study. We compared, in
      a non-human primate model, the lifelong growth trajectories of obese and non
      obese adults to assess the heritability of and map potential genomic regions
      implicated in growth and obesity. STUDY POPULATION: A total of 905 African green
      monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from
      a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown
      to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from
      2000 to 2015. We used a longitudinal clustering algorithm to detect obesogenic
      growth, and logistic growth curves implemented in nonlinear mixed effects models
      to estimate three growth parameters. We used maximum likelihood variance
      decomposition methods to estimate the genetic contributions to obesity-related
      traits and growth parameters, including a test for the effects of a calorie
      restricted dietary intervention. We used multipoint linkage analysis to map
      implicated genomic regions. RESULTS: All measurements were significantly
      influenced by sex, and with the exception of WC, also influenced by maternal and
      post-natal diet. Chronic obesity outcomes were significantly associated with a
      pattern of extended growth duration with slow growth rates for BW. After
      accounting for environmental influences, all measurements were found to have a
      significant genetic component to variability. Linkage analysis revealed several
      regions suggested to be linked to obesity-related traits that are also implicated
      in human obesity and metabolic disorders. CONCLUSIONS: As in humans, growth
      patterns in vervets have a significant impact on adult obesity and are largely
      under genetic control with some evidence for maternal and dietary programming.
      These results largely mirror findings from human research, but reflect shorter
      developmental periods, suggesting that the vervet offers a strong genetic model
      for elucidating the ontogeny of human obesity.

PMID- 29211708
TI  - Selective silencing of euchromatic L1s revealed by genome-wide screens for L1
      regulators.
AB  - Transposable elements, also known as transposons, are now recognized not only as
      parasitic DNA, the spread of which in the genome must be controlled by the host,
      but also as major players in genome evolution and regulation. Long interspersed
      element-1 (LINE-1, also known as L1), the only currently autonomous mobile
      transposon in humans, occupies 17% of the genome and generates inter- and intra
      individual genetic variation, in some cases resulting in disease. However, how L1
      activity is controlled and the function of L1s in host gene regulation are not
      completely understood. Here we use CRISPR-Cas9 screening strategies in two
      distinct human cell lines to provide a genome-wide survey of genes involved in
      the control of L1 retrotransposition. We identify functionally diverse genes that
      either promote or restrict L1 retrotransposition. These genes, which are often
      associated with human diseases, control the L1 life cycle at the transcriptional
      or the post-transcriptional level in a manner that can depend on the endogenous
      L1 nucleotide sequence, underscoring the complexity of L1 regulation. We further
      investigate the restriction of L1 by the protein MORC2 and by the human silencing
      hub (HUSH) complex subunits MPP8 and TASOR. HUSH and MORC2 can selectively bind
      evolutionarily young, full-length L1s located within transcriptionally permissive
      euchromatic environments, and promote deposition of histone H3 Lys9
      trimethylation (H3K9me3) for transcriptional silencing. Notably, these silencing
      events often occur within introns of transcriptionally active genes, and lead to
      the downregulation of host gene expression in a HUSH-, MORC2-, and L1-dependent
      manner. Together, these results provide a rich resource for studies of L1
      retrotransposition, elucidate a novel L1 restriction pathway and illustrate how
      epigenetic silencing of transposable elements rewires host gene expression
      programs.

PMID- 29211709
TI  - An 800-million-solar-mass black hole in a significantly neutral Universe at a
      redshift of 7.5.
AB  - Quasars are the most luminous non-transient objects known and as a result they
      enable studies of the Universe at the earliest cosmic epochs. Despite extensive
      efforts, however, the quasar ULAS J1120 + 0641 at redshift z = 7.09 has remained
      the only one known at z > 7 for more than half a decade. Here we report
      observations of the quasar ULAS J134208.10 + 092838.61 (hereafter J1342 + 0928)
      at redshift z = 7.54. This quasar has a bolometric luminosity of 4 * 1013 times
      the luminosity of the Sun and a black-hole mass of 8 * 108 solar masses. The
      existence of this supermassive black hole when the Universe was only 690 million
      years old-just five per cent of its current age-reinforces models of early black
      hole growth that allow black holes with initial masses of more than about 104
      solar masses or episodic hyper-Eddington accretion. We see strong evidence of
      absorption of the spectrum of the quasar redwards of the Lyman alpha emission
      line (the Gunn-Peterson damping wing), as would be expected if a significant
      amount (more than 10 per cent) of the hydrogen in the intergalactic medium
      surrounding J1342 + 0928 is neutral. We derive such a significant fraction of
      neutral hydrogen, although the exact fraction depends on the modelling. However,
      even in our most conservative analysis we find a fraction of more than 0.33
      (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing
      well within the reionization epoch of the Universe.

PMID- 29211710
TI  - Moving beyond microbiome-wide associations to causal microbe identification.
AB  - Microbiome-wide association studies have established that numerous diseases are
      associated with changes in the microbiota. These studies typically generate a
      long list of commensals implicated as biomarkers of disease, with no clear
      relevance to disease pathogenesis. If the field is to move beyond correlations
      and begin to address causation, an effective system is needed for refining this
      catalogue of differentially abundant microbes and to allow subsequent mechanistic
      studies. Here we demonstrate that triangulation of microbe-phenotype
      relationships is an effective method for reducing the noise inherent in
      microbiota studies and enabling identification of causal microbes. We found that
      gnotobiotic mice harbouring different microbial communities exhibited
      differential survival in a colitis model. Co-housing of these mice generated
      animals that had hybrid microbiotas and displayed intermediate susceptibility to
      colitis. Mapping of microbe-phenotype relationships in parental mouse strains and
      in mice with hybrid microbiotas identified the bacterial family Lachnospiraceae
      as a correlate for protection from disease. Using directed microbial culture
      techniques, we discovered Clostridium immunis, a previously unknown bacterial
      species from this family, that-when administered to colitis-prone mice-protected
      them against colitis-associated death. To demonstrate the generalizability of our
      approach, we used it to identify several commensal organisms that induce
      intestinal expression of an antimicrobial peptide. Thus, we have used microbe
      phenotype triangulation to move beyond the standard correlative microbiome study
      and identify causal microbes for two completely distinct phenotypes.
      Identification of disease-modulating commensals by microbe-phenotype
      triangulation may be more broadly applicable to human microbiome studies.

PMID- 29211711
TI  - KAT2A coupled with the alpha-KGDH complex acts as a histone H3
      succinyltransferase.
AB  - Histone modifications, such as the frequently occurring lysine succinylation, are
      central to the regulation of chromatin-based processes. However, the mechanism
      and functional consequences of histone succinylation are unknown. Here we show
      that the alpha-ketoglutarate dehydrogenase (alpha-KGDH) complex is localized in
      the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A,
      also known as GCN5) in the promoter regions of genes. We show that succinyl
      coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic
      domain of KAT2A in complex with succinyl-CoA at 2.3 A resolution shows that
      succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing
      towards the end of a flexible loop 3, which adopts different structural
      conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed
      mutagenesis indicates that tyrosine 645 in this loop has an important role in the
      selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a
      succinyltransferase and succinylates histone H3 on lysine 79, with a maximum
      frequency around the transcription start sites of genes. Preventing the alpha
      KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala),
      reduces gene expression and inhibits tumour cell proliferation and tumour growth.
      These findings reveal an important mechanism of histone modification and
      demonstrate that local generation of succinyl-CoA by the nuclear alpha-KGDH
      complex coupled with the succinyltransferase activity of KAT2A is instrumental in
      histone succinylation, tumour cell proliferation, and tumour development.

PMID- 29211712
TI  - Synchrotron scanning reveals amphibious ecomorphology in a new clade of bird-like
      dinosaurs.
AB  - Maniraptora includes birds and their closest relatives among theropod dinosaurs.
      During the Cretaceous period, several maniraptoran lineages diverged from the
      ancestral coelurosaurian bauplan and evolved novel ecomorphologies, including
      active flight, gigantism, cursoriality and herbivory. Propagation X-ray phase
      contrast synchrotron microtomography of a well-preserved maniraptoran from
      Mongolia, still partially embedded in the rock matrix, revealed a mosaic of
      features, most of them absent among non-avian maniraptorans but shared by
      reptilian and avian groups with aquatic or semiaquatic ecologies. This new
      theropod, Halszkaraptor escuilliei gen. et sp. nov., is related to other
      enigmatic Late Cretaceous maniraptorans from Mongolia in a novel clade at the
      root of Dromaeosauridae. This lineage adds an amphibious ecomorphology to those
      evolved by maniraptorans: it acquired a predatory mode that relied mainly on neck
      hyperelongation for food procurement, it coupled the obligatory bipedalism of
      theropods with forelimb proportions that may support a swimming function, and it
      developed postural adaptations convergent with short-tailed birds.

PMID- 29211713
TI  - Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours.
AB  - Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen
      exposure, where they elicit rapid and robust protective immune responses.
      However, the molecular signals that control TRM cell differentiation and
      homeostasis are not fully understood. Here we show that mouse TRM precursor cells
      represent a unique CD8+ T cell subset that is distinct from the precursors of
      circulating memory cell populations at the levels of gene expression and
      chromatin accessibility. Using computational and pooled in vivo RNA interference
      screens, we identify the transcription factor Runx3 as a key regulator of TRM
      cell differentiation and homeostasis. Runx3 was required to establish TRM cell
      populations in diverse tissue environments, and supported the expression of
      crucial tissue-residency genes while suppressing genes associated with tissue
      egress and recirculation. Furthermore, we show that human and mouse tumour
      infiltrating lymphocytes share a core tissue-residency gene-expression signature
      with TRM cells that is associated with Runx3 activity. In a mouse model of
      adoptive T cell therapy for melanoma, Runx3-deficient CD8+ tumour-infiltrating
      lymphocytes failed to accumulate in tumours, resulting in greater rates of tumour
      growth and mortality. Conversely, overexpression of Runx3 enhanced tumour
      specific CD8+ T cell abundance, delayed tumour growth, and prolonged survival. In
      addition to establishing Runx3 as a central regulator of TRM cell
      differentiation, these results provide insight into the signals that promote T
      cell residency in non-lymphoid sites, which could be used to enhance vaccine
      efficacy or adoptive cell therapy treatments that target cancer.

PMID- 29211714
TI  - Structures of the calcium-activated, non-selective cation channel TRPM4.
AB  - TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate
      (PtdIns(4,5)P2) -modulated, non-selective cation channel that belongs to the
      family of melastatin-related transient receptor potential (TRPM) channels. Here
      we present the electron cryo-microscopy structures of the mouse TRPM4 channel
      with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic
      domains, which assemble into a three-tiered architecture. The N-terminal
      nucleotide-binding domain and the C-terminal coiled-coil participate in the
      tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain
      and inhibits channel activity. TRPM4 has an exceptionally wide filter but is only
      permeable to monovalent cations; filter residue Gln973 is essential in defining
      monovalent selectivity. The S1-S4 domain and the post-S6 TRP domain form the
      central gating apparatus that probably houses the Ca2+- and PtdIns(4,5)P2-binding
      sites. These structures provide an essential starting point for elucidating the
      complex gating mechanisms of TRPM4 and reveal the molecular architecture of the
      TRPM family.

PMID- 29211715
TI  - Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.
AB  - Cancer incidence is rising and this global challenge is further exacerbated by
      tumour resistance to available medicines. A promising approach to meet the need
      for improved cancer treatment is drug repurposing. Here we highlight the
      potential for repurposing disulfiram (also known by the trade name Antabuse), an
      old alcohol-aversion drug that has been shown to be effective against diverse
      cancer types in preclinical studies. Our nationwide epidemiological study reveals
      that patients who continuously used disulfiram have a lower risk of death from
      cancer compared to those who stopped using the drug at their diagnosis. Moreover,
      we identify the ditiocarb-copper complex as the metabolite of disulfiram that is
      responsible for its anti-cancer effects, and provide methods to detect
      preferential accumulation of the complex in tumours and candidate biomarkers to
      analyse its effect on cells and tissues. Finally, our functional and biophysical
      analyses reveal the molecular target of disulfiram's tumour-suppressing effects
      as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for
      the turnover of proteins involved in multiple regulatory and stress-response
      pathways in cells.

PMID- 29211716
TI  - Atmospheric trace gases support primary production in Antarctic desert surface
      soil.
AB  - Cultivation-independent surveys have shown that the desert soils of Antarctica
      harbour surprisingly rich microbial communities. Given that phototroph abundance
      varies across these Antarctic soils, an enduring question is what supports life
      in those communities with low photosynthetic capacity. Here we provide evidence
      that atmospheric trace gases are the primary energy sources of two Antarctic
      surface soil communities. We reconstructed 23 draft genomes from metagenomic
      reads, including genomes from the candidate bacterial phyla WPS-2 and AD3. The
      dominant community members encoded and expressed high-affinity hydrogenases,
      carbon monoxide dehydrogenases, and a RuBisCO lineage known to support
      chemosynthetic carbon fixation. Soil microcosms aerobically scavenged atmospheric
      H2 and CO at rates sufficient to sustain their theoretical maintenance energy and
      mediated substantial levels of chemosynthetic but not photosynthetic CO2
      fixation. We propose that atmospheric H2, CO2 and CO provide dependable sources
      of energy and carbon to support these communities, which suggests that
      atmospheric energy sources can provide an alternative basis for ecosystem
      function to solar or geological energy sources. Although more extensive sampling
      is required to verify whether this process is widespread in terrestrial
      Antarctica and other oligotrophic habitats, our results provide new understanding
      of the minimal nutritional requirements for life and open the possibility that
      atmospheric gases support life on other planets.

PMID- 29211717
TI  - Force loading explains spatial sensing of ligands by cells.
AB  - Cells can sense the density and distribution of extracellular matrix (ECM)
      molecules by means of individual integrin proteins and larger, integrin
      containing adhesion complexes within the cell membrane. This spatial sensing
      drives cellular activity in a variety of normal and pathological contexts.
      Previous studies of cells on rigid glass surfaces have shown that spatial sensing
      of ECM ligands takes place at the nanometre scale, with integrin clustering and
      subsequent formation of focal adhesions impaired when single integrin-ligand
      bonds are separated by more than a few tens of nanometres. It has thus been
      suggested that a crosslinking 'adaptor' protein of this size might connect
      integrins to the actin cytoskeleton, acting as a molecular ruler that senses
      ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale
      distribution of ECM ligands can be controlled and altered. We find that
      increasing the spacing between ligands promotes the growth of focal adhesions on
      low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates.
      Furthermore, disordering the ligand distribution drastically increases adhesion
      growth, but reduces the rigidity threshold for adhesion collapse. The growth and
      collapse of focal adhesions are mirrored by, respectively, the nuclear or
      cytosolic localization of the transcriptional regulator protein YAP. We explain
      these findings not through direct sensing of ligand spacing, but by using an
      expanded computational molecular-clutch model, in which individual integrin-ECM
      bonds-the molecular clutches-respond to force loading by recruiting extra
      integrins, up to a maximum value. This generates more clutches, redistributing
      the overall force among them, and reducing the force loading per clutch. At high
      rigidity and high ligand spacing, maximum recruitment is reached, preventing
      further force redistribution and leading to adhesion collapse. Measurements of
      cellular traction forces and actin flow speeds support our model. Our results
      provide a general framework for how cells sense spatial and physical information
      at the nanoscale, precisely tuning the range of conditions at which they form
      adhesions and activate transcriptional regulation.

PMID- 29211718
TI  - piRNA-mediated regulation of transposon alternative splicing in the soma and germ
      line.
AB  - Transposable elements can drive genome evolution, but their enhanced activity is
      detrimental to the host and therefore must be tightly regulated. The Piwi
      interacting small RNA (piRNA) pathway is vital for the regulation of transposable
      elements, by inducing transcriptional silencing or post-transcriptional decay of
      mRNAs. Here we show that piRNAs and piRNA biogenesis components regulate
      precursor mRNA splicing of P-transposable element transcripts in vivo, leading to
      the production of the non-transposase-encoding mature mRNA isoform in Drosophila
      germ cells. Unexpectedly, we show that the piRNA pathway components do not act to
      reduce transcript levels of the P-element transposon during P-M hybrid
      dysgenesis, a syndrome that affects germline development in Drosophila. Instead,
      splicing regulation is mechanistically achieved together with piRNA-mediated
      changes to repressive chromatin states, and relies on the function of the Piwi
      piRNA complex proteins Asterix (also known as Gtsf1) and Panoramix (Silencio), as
      well as Heterochromatin protein 1a (HP1a; encoded by Su(var)205). Furthermore, we
      show that this machinery, together with the piRNA Flamenco cluster, not only
      controls the accumulation of Gypsy retrotransposon transcripts but also regulates
      the splicing of Gypsy mRNAs in cultured ovarian somatic cells, a process required
      for the production of infectious particles that can lead to heritable
      transposition events. Our findings identify splicing regulation as a new role and
      essential function for the Piwi pathway in protecting the genome against
      transposon mobility, and provide a model system for studying the role of
      chromatin structure in modulating alternative splicing during development.

PMID- 29211719
TI  - Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy.
AB  - Diabetic retinopathy is an important cause of blindness in adults, and is
      characterized by progressive loss of vascular cells and slow dissolution of inter
      vascular junctions, which result in vascular leakage and retinal oedema. Later
      stages of the disease are characterized by inflammatory cell infiltration, tissue
      destruction and neovascularization. Here we identify soluble epoxide hydrolase
      (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial
      barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid,
      derived from docosahexaenoic acid. The expression of sEH and the accumulation of
      19,20-dihydroxydocosapentaenoic acid were increased in diabetic mouse retinas and
      in the retinas and vitreous humour of patients with diabetes. Mechanistically,
      the diol targeted the cell membrane to alter the localization of cholesterol
      binding proteins, and prevented the association of presenilin 1 with N-cadherin
      and VE-cadherin, thereby compromising pericyte-endothelial cell interactions and
      inter-endothelial cell junctions. Treating diabetic mice with a specific sEH
      inhibitor prevented the pericyte loss and vascular permeability that are
      characteristic of non-proliferative diabetic retinopathy. Conversely,
      overexpression of sEH in the retinal Muller glial cells of non-diabetic mice
      resulted in similar vessel abnormalities to those seen in diabetic mice with
      retinopathy. Thus, increased expression of sEH is a key determinant in the
      pathogenesis of diabetic retinopathy, and inhibition of sEH can prevent
      progression of the disease.

PMID- 29211721
TI  - Galaxy growth in a massive halo in the first billion years of cosmic history.
AB  - According to the current understanding of cosmic structure formation, the
      precursors of the most massive structures in the Universe began to form shortly
      after the Big Bang, in regions corresponding to the largest fluctuations in the
      cosmic density field. Observing these structures during their period of active
      growth and assembly-the first few hundred million years of the Universe-is
      challenging because it requires surveys that are sensitive enough to detect the
      distant galaxies that act as signposts for these structures and wide enough to
      capture the rarest objects. As a result, very few such objects have been detected
      so far. Here we report observations of a far-infrared-luminous object at redshift
      6.900 (less than 800 million years after the Big Bang) that was discovered in a
      wide-field survey. High-resolution imaging shows it to be a pair of extremely
      massive star-forming galaxies. The larger is forming stars at a rate of 2,900
      solar masses per year, contains 270 billion solar masses of gas and 2.5 billion
      solar masses of dust, and is more massive than any other known object at a
      redshift of more than 6. Its rapid star formation is probably triggered by its
      companion galaxy at a projected separation of 8 kiloparsecs. This merging
      companion hosts 35 billion solar masses of stars and has a star-formation rate of
      540 solar masses per year, but has an order of magnitude less gas and dust than
      its neighbour and physical conditions akin to those observed in lower-metallicity
      galaxies in the nearby Universe. These objects suggest the presence of a dark
      matter halo with a mass of more than 100 billion solar masses, making it among
      the rarest dark-matter haloes that should exist in the Universe at this epoch.

PMID- 29211720
TI  - Blazar spectral variability as explained by a twisted inhomogeneous jet.
AB  - Blazars are active galactic nuclei, which are powerful sources of radiation whose
      central engine is located in the core of the host galaxy. Blazar emission is
      dominated by non-thermal radiation from a jet that moves relativistically towards
      us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement
      and contraction of the variability timescales, so that most blazars appear as
      luminous sources characterized by noticeable and fast changes in brightness at
      all frequencies. The mechanism that produces this unpredictable variability is
      under debate, but proposed mechanisms include injection, acceleration and cooling
      of particles, with possible intervention of shock waves or turbulence. Changes in
      the viewing angle of the observed emitting knots or jet regions have also been
      suggested as an explanation of flaring events and can also explain specific
      properties of blazar emission, such as intra-day variability, quasi-periodicity
      and the delay of radio flux variations relative to optical changes. Such a
      geometric interpretation, however, is not universally accepted because
      alternative explanations based on changes in physical conditions-such as the size
      and speed of the emitting zone, the magnetic field, the number of emitting
      particles and their energy distribution-can explain snapshots of the spectral
      behaviour of blazars in many cases. Here we report the results of optical-to
      radio-wavelength monitoring of the blazar CTA 102 and show that the observed long
      term trends of the flux and spectral variability are best explained by an
      inhomogeneous, curved jet that undergoes changes in orientation over time. We
      propose that magnetohydrodynamic instabilities or rotation of the twisted jet
      cause different jet regions to change their orientation and hence their relative
      Doppler factors. In particular, the extreme optical outburst of 2016-2017
      (brightness increase of six magnitudes) occurred when the corresponding emitting
      region had a small viewing angle. The agreement between observations and
      theoretical predictions can be seen as further validation of the relativistic
      beaming theory.

PMID- 29211722
TI  - Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity.
AB  - Alzheimer's disease is a common and devastating disease characterized by
      aggregation of the amyloid-beta peptide. However, we know relatively little about
      the underlying molecular mechanisms or how to treat patients with Alzheimer's
      disease. Here we provide bioinformatic and experimental evidence of a conserved
      mitochondrial stress response signature present in diseases involving amyloid
      beta proteotoxicity in human, mouse and Caenorhabditis elegans that involves the
      mitochondrial unfolded protein response and mitophagy pathways. Using a worm
      model of amyloid-beta proteotoxicity, GMC101, we recapitulated mitochondrial
      features and confirmed that the induction of this mitochondrial stress response
      was essential for the maintenance of mitochondrial proteostasis and health.
      Notably, increasing mitochondrial proteostasis by pharmacologically and
      genetically targeting mitochondrial translation and mitophagy increases the
      fitness and lifespan of GMC101 worms and reduces amyloid aggregation in cells,
      worms and in transgenic mouse models of Alzheimer's disease. Our data support the
      relevance of enhancing mitochondrial proteostasis to delay amyloid-beta
      proteotoxic diseases, such as Alzheimer's disease.

PMID- 29211723
TI  - Electron cryo-microscopy structure of a human TRPM4 channel.
AB  - Ca2+-activated, non-selective (CAN) ion channels sense increases of the
      intracellular Ca2+ concentration, producing a flux of Na+ and/or K+ ions that
      depolarizes the cell, thus modulating cellular Ca2+ entry. CAN channels are
      involved in cellular responses such as neuronal bursting activity and cardiac
      rhythm. Here we report the electron cryo-microscopy structure of the most
      widespread CAN channel, human TRPM4, bound to the agonist Ca2+ and the modulator
      decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure
      with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N
      terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like
      architecture. We observed two decavanadate-binding sites, one in the C-terminal
      domain and another in the intersubunit MHR interface. A glutamine in the
      selectivity filter may be an important determinant of monovalent selectivity. Our
      structure provides new insights into the function and pharmacology of both the
      CAN and the TRPM families.

PMID- 29211724
TI  - Large emissions from floodplain trees close the Amazon methane budget.
AB  - Wetlands are the largest global source of atmospheric methane (CH4), a potent
      greenhouse gas. However, methane emission inventories from the Amazon floodplain,
      the largest natural geographic source of CH4 in the tropics, consistently
      underestimate the atmospheric burden of CH4 determined via remote sensing and
      inversion modelling, pointing to a major gap in our understanding of the
      contribution of these ecosystems to CH4 emissions. Here we report CH4 fluxes from
      the stems of 2,357 individual Amazonian floodplain trees from 13 locations across
      the central Amazon basin. We find that escape of soil gas through wetland trees
      is the dominant source of regional CH4 emissions. Methane fluxes from Amazon tree
      stems were up to 200 times larger than emissions reported for temperate wet
      forests and tropical peat swamp forests, representing the largest non-ebullitive
      wetland fluxes observed. Emissions from trees had an average stable carbon
      isotope value (delta13C) of -66.2 +/- 6.4 per mil, consistent with a soil
      biogenic origin. We estimate that floodplain trees emit 15.1 +/- 1.8 to 21.2 +/-
      2.5 teragrams of CH4 a year, in addition to the 20.5 +/- 5.3 teragrams a year
      emitted regionally from other sources. Furthermore, we provide a 'top-down'
      regional estimate of CH4 emissions of 42.7 +/- 5.6 teragrams of CH4 a year for
      the Amazon basin, based on regular vertical lower-troposphere CH4 profiles
      covering the period 2010-2013. We find close agreement between our 'top-down' and
      combined 'bottom-up' estimates, indicating that large CH4 emissions from trees
      adapted to permanent or seasonal inundation can account for the emission source
      that is required to close the Amazon CH4 budget. Our findings demonstrate the
      importance of tree stem surfaces in mediating approximately half of all wetland
      CH4 emissions in the Amazon floodplain, a region that represents up to one-third
      of the global wetland CH4 source when trees are combined with other emission
      sources.

PMID- 29211725
TI  - Correction: Signatures of criticality arise from random subsampling in simple
      population models.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005718.].

PMID- 29211726
TI  - Psychosocial and socioeconomic determinants of cardiovascular mortality in
      Eastern Europe: A multicentre prospective cohort study.
AB  - BACKGROUND: Eastern European countries have some of the highest rates of
      cardiovascular disease (CVD) mortality, much of which cannot be adequately
      accounted for by conventional CVD risk factors. Psychosocial and socioeconomic
      factors may affect risk of CVD, but relatively few studies on this issue have
      been undertaken in Eastern Europe. We investigated whether various psychosocial
      factors are associated with CVD mortality independently from each other and
      whether they can help explain differences in CVD mortality between Eastern
      European populations. METHODS: Participants were from the Health, Alcohol and
      Psychological factors in Eastern Europe (HAPIEE) cohort study in Russia, Poland
      and the Czech Republic, including a total of 20,867 men and women aged 43-74
      years and free of CVD at baseline examination during 2002-2005. Participants were
      followed-up for CVD mortality after linkage to national mortality registries for
      a median of 7.2 years. RESULTS: During the follow-up, 556 participants died from
      CVD. After mutual adjustment, six psychosocial and socioeconomic factors were
      associated with increased risk of CVD death: unemployment, low material
      amenities, depression, being single, infrequent contacts with friends or
      relatives. The hazard ratios [HRs] for these six factors ranged between 1.26 [95%
      confidence interval 1.14-1.40] and 1.81 [95% confidence interval 1.24-2.64],
      fully adjusted for each other, and conventional cardiovascular risk factors.
      Population-attributable fractions ranged from 8% [4%-13%] to 22% [11%-31%] for
      each factor, when measured on average across the three cohorts. However, the
      prevalence of psychosocial and socioeconomic risk factors and their HRs were
      similar between the three countries. Altogether, these factors could not explain
      why participants from Russia had higher CVD mortality when compared to
      participants from Poland/Czech Republic. Limitations of this study include
      measurement error that could lead to residual confounding; and the possibilities
      for reverse causation and/or unmeasured confounding from observational studies to
      lead to associations that are not causal in nature. CONCLUSIONS: Six psychosocial
      and socioeconomic factors were associated with cardiovascular mortality,
      independent of each other. Differences in mortality between cohorts from Russia
      versus Poland or Check Republic remained unexplained.

PMID- 29211727
TI  - Playing Super Mario 64 increases hippocampal grey matter in older adults.
AB  - Maintaining grey matter within the hippocampus is important for healthy
      cognition. Playing 3D-platform video games has previously been shown to promote
      grey matter in the hippocampus in younger adults. In the current study, we tested
      the impact of 3D-platform video game training (i.e., Super Mario 64) on grey
      matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex
      (DLPFC) of older adults. Older adults who were 55 to 75 years of age were
      randomized into three groups. The video game experimental group (VID; n = 8)
      engaged in a 3D-platform video game training over a period of 6 months.
      Additionally, an active control group took a series of self-directed,
      computerized music (piano) lessons (MUS; n = 12), while a no-contact control
      group did not engage in any intervention (CON; n = 13). After training, a within
      subject increase in grey matter within the hippocampus was significant only in
      the VID training group, replicating results observed in younger adults. Active
      control MUS training did, however, lead to a within-subject increase in the
      DLPFC, while both the VID and MUS training produced growth in the cerebellum. In
      contrast, the CON group displayed significant grey matter loss in the
      hippocampus, cerebellum and the DLPFC.

PMID- 29211728
TI  - An open-label, non-randomized study of the pharmacokinetics of the nutritional
      supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in
      healthy volunteers.
AB  - OBJECTIVES: The co-primary objectives of this study were to determine the human
      pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide
      adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction
      plays a critical role in the development and progression of heart failure, no
      mitochondria-targeted therapies have been translated into clinical practice.
      Recent murine studies have reported associations between imbalances in the
      NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including
      myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved
      cardiac function, while another NAD+ precursor, nicotinamide riboside (NR),
      improved mitochondrial function in muscle, liver and brown adipose. Thus, PK
      studies of NR in humans is critical for future clinical trials. METHODS: In this
      non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally
      administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily
      on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study
      after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood
      chemistry, and NAD+ levels were analyzed. RESULTS: Oral NR was well tolerated
      with no adverse events. Significant increases comparing baseline to mean
      concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and
      NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to
      Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008).
      CONCLUSIONS: Because NR increases circulating NAD+ in humans, NR may have
      potential as a therapy in patients with mitochondrial dysfunction due to genetic
      and/or acquired diseases.

PMID- 29211729
TI  - A promoter variant of the APOA5 gene increases atherogenic LDL levels and
      arterial stiffness in hypertriglyceridemic patients.
AB  - Hypertriglyceridemia is recognized as an independent risk factor for coronary
      artery disease. The apolipoprotein A5 gene (APOA5) is a key regulator of
      triglyceride levels. We aimed to evaluate the associations of single nucleotide
      polymorphisms (SNPs) in APOA5, including -1131T>C and c.553G>T, with
      hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels,
      and arterial stiffness in hypertriglyceridemic patients. The study population
      included 599 hypertriglyceridemic patients (case) and 1,549 untreated
      normotriglyceridemic subjects (control). We genotyped two APOA5 variants, 
      1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype
      of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly
      higher in hypertriglyceridemic patients than in normotriglyceridemic subjects
      (0.061 and 0.070, respectively; all p<0.001). In the control and case groups,
      both the -1131T>C and c.553G>T variants were associated with higher triglyceride
      and lower HDL cholesterol levels. Controls with the -1131CC variant had lower
      apoA5 concentrations than controls with the -1131TT variant. Similar effects of
      the -1131T>C variant on apoA5 were observed in the cases. In the
      hypertriglyceridemic group, the -1131T>C variant was associated with a smaller
      LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher
      brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were
      associated with hypertriglyceridemia in the study population, but only the 
      1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic
      patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic
      LDL levels and arterial stiffness, probably due to an effect of the -1131T>C
      polymorphism on apoA5 concentrations.

PMID- 29211730
TI  - A continuous morphological approach to study the evolution of pollen in a
      phylogenetic context: An example with the order Myrtales.
AB  - The study of pollen morphology has historically allowed evolutionary biologists
      to assess phylogenetic relationships among Angiosperms, as well as to better
      understand the fossil record. During this process, pollen has mainly been studied
      by discretizing some of its main characteristics such as size, shape, and exine
      ornamentation. One large plant clade in which pollen has been used this way for
      phylogenetic inference and character mapping is the order Myrtales, composed by
      the small families Alzateaceae, Crypteroniaceae, and Penaeaceae (collectively the
      "CAP clade"), as well as the large families Combretaceae, Lythraceae,
      Melastomataceae, Myrtaceae, Onagraceae and Vochysiaceae. In this study, we
      present a novel way to study pollen evolution by using quantitative size and
      shape variables. We use morphometric and morphospace methods to evaluate pollen
      change in the order Myrtales using a time-calibrated, supermatrix phylogeny. We
      then test for conservatism, divergence, and morphological convergence of pollen
      and for correlation between the latitudinal gradient and pollen size and shape.
      To obtain an estimate of shape, Myrtales pollen images were extracted from the
      literature, and their outlines analyzed using elliptic Fourier methods. Shape and
      size variables were then analyzed in a phylogenetic framework under an Ornstein
      Uhlenbeck process to test for shifts in size and shape during the evolutionary
      history of Myrtales. Few shifts in Myrtales pollen morphology were found which
      indicates morphological conservatism. Heterocolpate, small pollen is ancestral
      with largest pollen in Onagraceae. Convergent shifts in shape but not size
      occurred in Myrtaceae and Onagraceae and are correlated to shifts in latitude and
      biogeography. A quantitative approach was applied for the first time to examine
      pollen evolution across a large time scale. Using phylogenetic based
      morphometrics and an OU process, hypotheses of pollen size and shape were tested
      across Myrtales. Convergent pollen shifts and position in the latitudinal
      gradient support the selective role of harmomegathy, the mechanism by which
      pollen grains accommodate their volume in response to water loss.

PMID- 29211731
TI  - Social mixing in Fiji: Who-eats-with-whom contact patterns and the implications
      of age and ethnic heterogeneity for disease dynamics in the Pacific Islands.
AB  - Empirical data on contact patterns can inform dynamic models of infectious
      disease transmission. Such information has not been widely reported from Pacific
      islands, nor strongly multi-ethnic settings, and few attempts have been made to
      quantify contact patterns relevant for the spread of gastrointestinal infections.
      As part of enteric fever investigations, we conducted a cross-sectional survey of
      the general public in Fiji, finding that within the 9,650 mealtime contacts
      reported by 1,814 participants, there was strong like-with-like mixing by age and
      ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians.
      Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the
      overall data do not simply reflect household structures. Inter-ethnic mixing was
      most common amongst school-age children. Serological responses indicative of
      recent Salmonella Typhi infection were found to be associated, after adjusting
      for age, with increased contact rates between meal-sharing iTaukei, with no
      association observed for other contact groups. Animal ownership and travel within
      the geographical division were common. These are novel data that identify
      ethnicity as an important social mixing variable, and use retrospective mealtime
      contacts as a socially acceptable metric of relevance to enteric, contact and
      respiratory diseases that can be collected in a single visit to participants.
      Application of these data to other island settings will enable communicable
      disease models to incorporate locally relevant mixing patterns in
      parameterisation.

PMID- 29211733
TI  - Correction: Underestimation of Leptospirosis Incidence in the French West Indies.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0004668.].

PMID- 29211732
TI  - The mouse Jhy gene regulates ependymal cell differentiation and ciliogenesis.
AB  - During the first postnatal week of mouse development, radial glial cells lining
      the ventricles of the brain differentiate into ependymal cells, undergoing a
      morphological change from pseudostratified cuboidal cells to a flattened
      monolayer. Concomitant with this change, multiple motile cilia are generated and
      aligned on each nascent ependymal cell. Proper ependymal cell development is
      crucial to forming the brain tissue:CSF barrier, and to the establishment of
      ciliary CSF flow, but the mechanisms that regulate this differentiation event are
      poorly understood. The JhylacZ mouse line carries an insertional mutation in the
      Jhy gene (formerly 4931429I11Rik), and homozygous JhylacZ/lacZ mice develop a
      rapidly progressive juvenile hydrocephalus, with defects in ependymal cilia
      morphology and ultrastructure. Here we show that beyond just defective motile
      cilia, JhylacZ/lacZ mice display abnormal ependymal cell differentiation.
      Ventricular ependyma in JhylacZ/lacZ mice retain an unorganized and multi-layered
      morphology, representative of undifferentiated ependymal (radial glial) cells,
      and they show altered expression of differentiation markers. Most JhylacZ/lacZ
      ependymal cells do eventually acquire some differentiated ependymal
      characteristics, suggesting a delay, rather than a block, in the differentiation
      process, but ciliogenesis remains perturbed. JhylacZ/lacZ ependymal cells also
      manifest disruptions in adherens junction formation, with altered N-cadherin
      localization, and have defects in the polarized organization of the apical motile
      cilia that do form. Functional studies showed that cilia of JhylacZ/lacZ mice
      have severely reduced motility, a potential cause for the development of
      hydrocephalus. This work shows that JHY does not only control ciliogenesis, but
      is a crucial component of the ependymal differentiation process, with ciliary
      defects likely a consequence of altered ependymal differentiation.

PMID- 29211734
TI  - Seafarer citizen scientist ocean transparency data as a resource for
      phytoplankton and climate research.
AB  - The oceans' phytoplankton that underpin the marine food chain appear to be
      changing in abundance due to global climate change. Here, we compare the first
      four years of data from a citizen science ocean transparency study, conducted by
      seafarers using home-made Secchi Disks and a free Smartphone application called
      Secchi, with contemporaneous satellite ocean colour measurements. Our results
      show seafarers collect useful Secchi Disk measurements of ocean transparency that
      could help future assessments of climate-induced changes in the phytoplankton
      when used to extend historical Secchi Disk data.

PMID- 29211735
TI  - 'Lowering the threshold of effective deterrence'-Testing the effect of private
      security agents in public spaces on crime: A randomized controlled trial in a
      mass transit system.
AB  - Supplementing local police forces is a burgeoning multibillion-dollar private
      security industry. Millions of formal surveillance agents in public settings are
      tasked to act as preventative guardians, as their high visibility presence is
      hypothesized to create a deterrent threat to potential offenders. Yet, rigorous
      evidence is lacking. We randomly assigned all train stations in the South West of
      England that experienced crime into treatment and controls conditions over a six
      month period. Treatment consisted of directed patrol by uniformed, unarmed
      security agents. Hand-held trackers on every agent yielded precise measurements
      of all patrol time in the stations. Count-based regression models, estimated
      marginal means and odds-ratios are used to assess the effect of these patrols on
      crimes reported to the police by victims, as well as new crimes detected by
      police officers. Outcomes are measured at both specified target locations to
      which security guards were instructed to attend, as well as at the entire station
      complexes. Analyses show that 41% more patrol visits and 29% more minutes spent
      by security agents at treatment compared to control stations led to a significant
      16% reduction in victim-generated crimes at the entirety of the stations'
      complexes, with a 49% increase in police-generated detections at the target
      locations. The findings illustrate the efficacy of private policing for crime
      prevention theory.

PMID- 29211736
TI  - Versatile single-step-assembly CRISPR/Cas9 vectors for dual gRNA expression.
AB  - CRISPR/Cas9 technology enables efficient, rapid and cost-effective targeted
      genomic modification in a wide variety of cellular contexts including cultured
      cells. Some applications such as generation of double knock-outs, large deletions
      and paired-nickase cleavage require simultaneous expression of two gRNAs.
      Although single plasmids that enable multiplex expression of gRNAs have been
      developed, these require multiple rounds of cloning and/or PCR for generation of
      the desired construct. Here, we describe a series of vectors that enable
      generation of customized dual-gRNA expression constructs via an easy one-step
      golden gate cloning reaction using two annealed oligonucleotide inserts with
      different overhangs. Through nucleofection of mouse embryonic stem cells, we
      demonstrate highly efficient cleavage of the target loci using the dual-guide
      plasmids, which are available as Cas9-nuclease or Cas9-nickase expression
      constructs, with or without selection markers. These vectors are a valuable
      addition to the CRISPR/Cas9 toolbox and will be made available to all interested
      researchers via the Addgene plasmid repository.

PMID- 29211737
TI  - Correction: CD8+ T cells provide immune protection against murine disseminated
      endotheliotropic Orientia tsutsugamushi infection.
AB  - [This corrects the article DOI: 10.1371/journal.pntd.0005763.].

PMID- 29211739
TI  - The association between socioeconomic factors and breast cancer-specific survival
      varies by race.
AB  - Although racial disparity is well described for oncologic outcomes, factors
      associated with survival within racial groups remains unexplored. The objective
      of this study is to determine whether breast cancer survival among White or Black
      patients is associated with differing patient factors. Women diagnosed with
      breast cancer from 1998 through 2012 were identified in the Surveillance,
      Epidemiology, and End Results (SEER) database. Cox proportional hazard logistic
      regression was used to estimate cause-specific survival in the combined cohort,
      and separate cohorts of Black or White patients only. Main outcomes included
      cause-specific survival in cohorts of Black only, White only, or all patients
      adjusted for demographic and oncologic factors. A total of 406,907 Black (10.8%)
      or White (89.2%) patients diagnosed with breast cancer from 1998 through 2012
      were isolated. Cancer-specific survival analysis of the combined cohort showed
      significantly decreased hazard ratio (H.R.) in patients from the higher economic
      quartiles (Q1: 1.0 (ref), Q2: 0.95 (p<0.01), Q3: 0.94 (p<0.01), Q4: 0.87
      (p<0.001)). Analysis of the White only cohort showed a similar relationship with
      income (Q1: 1.0 (ref), Q2: 0.95 (p<0.01), Q3: 0.95 (p<0.01), Q4: 0.86 (p<0.001)).
      However, analysis of the Black only cohort did not show a relationship with
      income (Q1: 1.0 (ref), Q2: 1.04 (p = 0.34), Q3: 0.97 (p = 0.53), Q4: 1.04 (p =
      0.47)). A test of interaction confirmed that the association between income and
      cancer-specific survival is dependent on patient race, both with and without
      adjustment for demographic and oncologic characteristics (p<0.01). While median
      county income is positively associated with cancer-specific survival among White
      patients, this is not the case with Black patients. Similar findings were noted
      for education level. These findings suggest that the association between
      socioeconomic status and breast cancer survival commonly reported in the
      literature is specific to White patients. These findings provide insight into
      differences between White and Black patients in cancer-specific survival.

PMID- 29211738
TI  - Metformin inhibits the development, and promotes the resensitization, of
      treatment-resistant breast cancer.
AB  - Multiple drug resistant (MDR) malignancy remains a predictable and often terminal
      event in cancer therapy, and affects individuals with many cancer types,
      regardless of the stage at which they were originally diagnosed or the interval
      from last treatment. Protein biomarkers of MDR are not globally used for clinical
      decision-making, but include the overexpression of drug-efflux pumps (ABC
      transporter family) such as MDR-1 and BCRP, as well as HIF1alpha, a stress
      responsive transcription factor found elevated within many MDR tumors. Here, we
      present the important in vitro discovery that the development of MDR (in breast
      cancer cells) can be prevented, and that established MDR could be resensitized to
      therapy, by adjunct treatment with metformin. Metformin is prescribed globally to
      improve insulin sensitivity, including in those individuals with Type 2 Diabetes
      Mellitus (DM2). We demonstrate the effectiveness of metformin in resensitizing
      MDR breast cancer cell lines to their original treatment, and provide evidence
      that metformin may function through a mechanism involving post-translational
      histone modifications via an indirect histone deacetylase inhibitor (HDACi)
      activity. We find that metformin, at low physiological concentrations, reduces
      the expression of multiple classic protein markers of MDR in vitro and in
      preliminary in vivo models. Our demonstration that metformin can prevent MDR
      development and resensitize MDR cells to chemotherapy in vitro, provides
      important medical relevance towards metformin's potential clinical use against
      MDR cancers.

PMID- 29211740
TI  - A systematic review and meta-analysis of comprehensive interventions for pre
      school children with autism spectrum disorder (ASD).
AB  - BACKGROUND: There has an increasing number of published trials on psychosocial
      intervention programmes for pre-school children with autism spectrum disorder
      (ASD). To achieve better quality of unbiased evidence for the effectiveness of
      ASD interventions, it is necessary to conduct a comprehensive review that covers
      studies with adequate quality standards, such as randomised controlled trials
      (RCTs), and different types of intervention In this study, we categorize
      interventions for ASD as behavioural, social-communication focused, and
      multimodal developmental based on Howlin's classification of early interventions
      for children with ASD. The aim of this study was to compare these three models
      and investigate the strengths and weaknesses of each type of intervention and to
      identify the approaches that contribute to a successful outcome for children with
      autism. METHODS: We performed a systematic review and meta-analysis. We included
      RCTs targeting children with ASD 6 years old or younger. A random effects model
      was used to present the effect estimate for the outcomes. This study also
      performed combined meta-analyses of all the three models to investigate the
      overall effectiveness of the intervention programmes. RESULTS: 32 randomized
      controlled studies were found to be eligible for inclusion. The synthesized data
      included 594 children from 14 RCTs. There was no statistically significant
      difference in the effects on autism general symptoms between the social
      communication-focused model and the multimodal developmental model (p = 0.83).
      The results suggest that there is evidence of an effect on 'reciprocity of social
      interaction towards others' (standard mean difference [95% confidential interval]
      = 0.53[0.29,0.78], p<0.01) and 'parental synchrony' (SMD = 0.99[0.70,1.29],
      p<0.01). CONCLUSION: The small number of studies included in the present study
      limited the ability to make inferences when comparing the three models and
      investigating the strengths and weaknesses of each type of intervention with
      respect to important outcomes. Since the outcome of 'reciprocity of social
      interaction towards others' could be a dependent variable that might be context
      bound to interactions with the child's parent, we cannot conclude the
      interventions for pre-school children with ASD have significant effects on a
      generalized skill to engage in reciprocal interactions with others. However, the
      outcomes of 'reciprocity of social interaction towards others' and 'parental
      synchrony' may be promising targets for interventions involving pre-school
      children with ASD. TRIAL REGISTRATION: Prospero CRD42011001349.

PMID- 29211742
TI  - Fear of falling and postural reactivity in patients with glaucoma.
AB  - PURPOSE: To investigate the relationship between postural metrics obtained by
      dynamic visual stimulation in a virtual reality environment and the presence of
      fear of falling in glaucoma patients. METHODS: This cross-sectional study
      included 35 glaucoma patients and 26 controls that underwent evaluation of
      postural balance by a force platform during presentation of static and dynamic
      visual stimuli with head-mounted goggles (Oculus Rift). In dynamic condition, a
      peripheral translational stimulus was used to induce vection and assess postural
      reactivity. Standard deviations of torque moments (SDTM) were calculated as
      indicative of postural stability. Fear of falling was assessed by a standardized
      questionnaire. The relationship between a summary score of fear of falling and
      postural metrics was investigated using linear regression models, adjusting for
      potentially confounding factors. RESULTS: Subjects with glaucoma reported greater
      fear of falling compared to controls (-0.21 vs. 0.27; P = 0.039). In glaucoma
      patients, postural metrics during dynamic visual stimulus were more associated
      with fear of falling (R2 = 18.8%; P = 0.001) than static (R2 = 3.0%; P = 0.005)
      and dark field (R2 = 5.7%; P = 0.007) conditions. In the univariable model, fear
      of falling was not significantly associated with binocular standard perimetry
      mean sensitivity (P = 0.855). In the multivariable model, each 1 Nm larger SDTM
      in anteroposterior direction during dynamic stimulus was associated with a
      worsening of 0.42 units in the fear of falling questionnaire score (P = 0.001).
      CONCLUSION: In glaucoma patients, postural reactivity to a dynamic visual
      stimulus using a virtual reality environment was more strongly associated with
      fear of falling than visual field testing and traditional balance assessment.

PMID- 29211741
TI  - An economic evaluation of Alexander Technique lessons or acupuncture sessions for
      patients with chronic neck pain: A randomized trial (ATLAS).
AB  - OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and
      Alexander Technique lessons and usual care, compared with usual GP care alone for
      chronic neck pain patients. METHODS: An economic evaluation was undertaken
      alongside the ATLAS trial, taking both NHS and wider societal viewpoints.
      Participants were offered up to twelve acupuncture sessions or twenty Alexander
      lessons (equivalent overall contact time). Costs were in pounds sterling.
      Effectiveness was measured using the generic EQ-5D to calculate quality adjusted
      life years (QALYs), as well as using a specific neck pain measure-the Northwick
      Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis,
      incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander
      groups, respectively, in comparison to usual GP care, indicating moderate health
      benefits for both interventions. Incremental costs were L451 for acupuncture and
      L667 for Alexander, mainly driven by intervention costs. Acupuncture was likely
      to be cost-effective (ICER = L18,767/QALY bootstrapped 95% CI L4,426 to L74,562)
      and was robust to most sensitivity analyses. Alexander lessons were not cost
      effective at the lower NICE threshold of L20,000/QALY (L25,101/QALY bootstrapped
      95% CI -L150,208 to L248,697) but may be at L30,000/QALY, however, there was
      considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In
      comparison with usual care, acupuncture is likely to be cost-effective for
      chronic neck pain, whereas, largely due to higher intervention costs, Alexander
      lessons are unlikely to be cost-effective. However, there were high levels of
      missing data and further research is needed to assess the long-term cost
      effectiveness of these interventions.

PMID- 29211743
TI  - Symptoms associated with adverse dengue fever prognoses at the time of reporting
      in the 2015 dengue outbreak in Taiwan.
AB  - BACKGROUND: Tainan experienced the most severe dengue epidemic in Taiwan in 2015.
      This study investigates the association between the signs and symptoms at the
      time of reporting with the adverse dengue prognoses. METHODS: A descriptive study
      was conducted using secondary data from the Dengue Disease Reporting System in
      Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise
      logistic regression was used to identify the risk factors for the adverse
      prognoses: ICU admissions and mortality. RESULTS: There were 22,777 laboratory
      confirmed reported cases (mean age 45.6 +/- 21.2 years), of which 3.7% were
      admitted to intensive care units (ICU), and 0.8% were fatal. The most common
      symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The
      prevalence of respiratory distress, altered consciousness, shock, bleeding, and
      thrombocytopenia increased with age. The multivariate analysis indicated that
      being in 65-89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90
      years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90)
      and respiratory distress (aOR: 5.31) were significantly associated with the risk
      of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66),
      altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were
      significantly associated with the risk of mortality. CONCLUSIONS: Dengue patients
      older than 65 and those with severe and non-specific signs and symptoms at the
      time of reporting were at a higher risk of ICU admission and mortality. First
      line healthcare providers need to be aware of the varied presentations between
      the different age groups to allow early diagnosis and in-time management, which
      would prevent ICU admissions and fatalities in dengue patients.

PMID- 29211744
TI  - Authorship and citation manipulation in academic research.
AB  - Some scholars add authors to their research papers or grant proposals even when
      those individuals contribute nothing to the research effort. Some journal editors
      coerce authors to add citations that are not pertinent to their work and some
      authors pad their reference lists with superfluous citations. How prevalent are
      these types of manipulation, why do scholars stoop to such practices, and who
      among us is most susceptible to such ethical lapses? This study builds a
      framework around how intense competition for limited journal space and research
      funding can encourage manipulation and then uses that framework to develop
      hypotheses about who manipulates and why they do so. We test those hypotheses
      using data from over 12,000 responses to a series of surveys sent to more than
      110,000 scholars from eighteen different disciplines spread across science,
      engineering, social science, business, and health care. We find widespread
      misattribution in publications and in research proposals with significant
      variation by academic rank, discipline, sex, publication history, co-authors,
      etc. Even though the majority of scholars disapprove of such tactics, many feel
      pressured to make such additions while others suggest that it is just the way the
      game is played. The findings suggest that certain changes in the review process
      might help to stem this ethical decline, but progress could be slow.

PMID- 29211745
TI  - The Back Belief Questionnaire is efficient to assess false beliefs and related
      fear in low back pain populations: A transcultural adaptation and validation
      study.
AB  - BACKGROUND: According to the fear avoidance model, beliefs and thoughts can
      modify the outcome of patient with low back pain. The Back Belief Questionnaire
      (BBQ)-a 14 items scale-assesses these consequences of low back pain. OBJECTIVE:
      To test the psychometric properties of the French version of the BBQ. METHODS:
      The BBQ was translated using the forward-backward translation process. Throughout
      three repeated evaluation time points (D1, D7 and D30), various aspects of
      validity were analysed: acceptability, quality of items, unidimentionality,
      internal consistency, temporal stability (between D1 and D7), responsiveness
      (between D7 and D30), and construct validity comparing it to other validated
      scales. RESULTS: One hundred and thirty-one patients were enrolled and 128 were
      analyzed. The acceptability and the quality of the items were excellent. The
      scale was unidimensional and reliable (internal consistency: Cronbach's alpha =
      0.8). The responsiveness was moderate but in line with other scores. The BBQ was,
      as expected, convergent with day-to-day activities and fear avoidance (FABQ and
      Tampa), disability (Quebec and Dallas scores), or anxiety and depression (HAD);
      and not correlated with pain. Best correlations were found with Tampa and FABQ.
      The temporal stability (test-retest reliability) was poor. However, similar
      changes were observed in near conceptual score (FABQ), which confirmed that
      clinical status may have not been stable and suggesting sensitivity to early
      changes for BBQ. CONCLUSIONS: The BBQ showed good psychometric properties to
      assess false beliefs and related fear in French or English LBP populations and
      can be used either for evaluation in international trials or as a part of self
      care training.

PMID- 29211747
TI  - Profiling of volatile fragrant components in a mini-core collection of mango
      germplasms from seven countries.
AB  - Aroma is important in assessing the quality of fresh fruit and their processed
      products, and could provide good indicators for the development of local
      cultivars in the mango industry. In this study, the volatile diversity of 25
      mango cultivars from China, America, Thailand, India, Cuba, Indonesia, and the
      Philippines was investigated. The volatile compositions, their relative contents,
      and the intervarietal differences were detected with headspace solid phase
      microextraction tandem gas chromatography-mass spectrometer methods. The
      similarities were also evaluated with a cluster analysis and correlation analysis
      of the volatiles. The differences in mango volatiles in different districts are
      also discussed. Our results show significant differences in the volatile
      compositions and their relative contents among the individual cultivars and
      regions. In total, 127 volatiles were found in all the cultivars, belonging to
      various chemical classes. The highest and lowest qualitative abundances of
      volatiles were detected in 'Zihua' and 'Mallika' cultivars, respectively. Based
      on the cumulative occurrence of members of the classes of volatiles, the
      cultivars were grouped into monoterpenes (16 cultivars), proportion and balanced
      (eight cultivars), and nonterpene groups (one cultivars). Terpene hydrocarbons
      were the major volatiles in these cultivars, with terpinolene, 3-carene,
      caryophyllene and alpha-Pinene the dominant components depending on the
      cultivars. Monoterpenes, some of the primary volatile components, were the most
      abundant aroma compounds, whereas aldehydes were the least abundant in the mango
      pulp. beta-Myrcene, a major terpene, accounted for 58.93% of the total flavor
      volatile compounds in 'Xiaofei' (Philippens). gamma-Octanoic lactone was the only
      ester in the total flavor volatile compounds, with its highest concentration in
      'Guiya' (China). Hexamethyl cyclotrisiloxane was the most abundant volatile
      compound in 'Magovar' (India), accounting for 46.66% of the total flavor
      volatiles. A typical aldehydic aroma 2,6-di-tert-butyl-4-sec-butylphenol, was
      detected in 'Gleck'. A highly significant positive correlation was detected
      between Alc and K, Alk and Nt, O and L. Cultivars originating from America,
      Thailand, Cuba, India, Indonesia and the Philippines were more similar to each
      other than to those from China. This study provides a high-value dataset for use
      in development of health care products, diversified mango breeding, and local
      extension of mango cultivars.

PMID- 29211746
TI  - Review of the factors influencing the motivation of community drug distributors
      towards the control and elimination of neglected tropical diseases (NTDs).
AB  - BACKGROUND: Community drug distributors or neglected tropical disease (NTD)
      volunteers have played a crucial role in ensuring the success of mass drug
      administration (MDA) programs using preventive chemotherapy (PC) for lymphatic
      filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted
      helminths. In recent years however, a noticeable decline in motivation of some of
      these volunteers has been perceived, potentially negatively impacting the success
      of these programs. Potential hypotheses for this change in motivation include the
      long duration of many MDA programs, the change in sociocultural environments as
      well as the changes to the programs over time. This literature review identifies
      factors that affect NTD volunteer performance and motivation, which may be used
      to influence and improve future programming. METHODOLOGY/PRINCIPAL FINDINGS: A
      systematic search was conducted to identify studies published between January
      1995 and September 2016 that investigate factors pertaining to volunteer
      motivation and performance in NTD drug distribution programs. Searches from
      several databases and grey literature yielded 400 records, of which 28 articles
      from 10 countries met the inclusion criteria. Quality assessment of studies was
      performed using the Critical Appraisal Skills Programme(CASP) checklist. Data
      pertaining to motivation, performance, retention and satisfaction was extracted
      and examined for themes. Recurring themes in the literature included monetary and
      material incentives, intrinsic motivation, gender, cost to participate, and
      health systems and community support. Of these, community support and the health
      system were found to be particularly impactful. Very few studies were found to
      explicitly look at novel incentives for volunteers and very few studies have
      considered the out of pocket and opportunity costs that NTD volunteers bear
      carrying out their tasks. CONCLUSIONS/SIGNIFICANCE: There is currently great
      interest in incorporating more attractive incentive schemes for NTD volunteers.
      However, our results show that the important challenges that volunteers face
      (cultural, health systems, financial and community related) may have less to do
      with financial incentives and may actually have a larger impact on their
      motivation than has previously been understood. Further integration of NTD
      programs into existing health systems is expected to improve the NTD volunteer
      working environment. Relevant community engagement related to the MDA program
      should also provide the supportive environment needed in the community to support
      NTD volunteers. Programs need to consider these issues to improve working
      conditions for NTD volunteers.

PMID- 29211748
TI  - Interactions between abundant fungal species influence the fungal community
      assemblage on limestone.
AB  - The assembly of fungal communities on stone materials is mainly influenced by the
      differential bioreceptivity of such materials and environmental conditions.
      However, little is known about the role of fungal interactions in the
      colonization and establishment of fungal species. We analyzed the effects of
      intra- and interspecific interactions between 11 species of fungi in oligotrophic
      and copiotrophic media and on limestone coupons. In a previous study, these
      species were the most frequently isolated in the epilithic biofilms of limestone
      walls exposed to a subtropical climate. In the culture media, we found a greater
      frequency of intra- and interspecific inhibitory effects in the oligotrophic
      medium than in the copiotrophic medium. On the limestone coupons, all fungi were
      able to establish; however, the colonization success rate varied significantly.
      Cladosporium cladosporioides had a less extensive colonization in isolation
      (control) than in dual interactions (coexistence) with other species. Phoma
      eupyrena exhibited the highest colonization success rate and competitive
      dominance among all tested species. X-ray diffraction (XRD) and scanning electron
      microscope (SEM) analyses revealed that Pestalotiopsis maculans and
      Paraconiothyrium sp. produced calcium oxalate crystals during their growth on
      coupon surfaces, both in isolation and in dual interactions. Our results
      demonstrate that interactions between abundant fungal species influence the
      fungal colonization on substrates, the biomineralization and the fungal community
      assemblage growing in limestone biofilms.

PMID- 29211749
TI  - Stone heat treatment in the Early Mesolithic of southwestern Germany:
      Interpretation and identification.
AB  - The Early Mesolithic of southwestern Germany, the so-called Beuronian (9600-7100
      BC), is a period of important transformations in the way people lived, in their
      subsistence and in the stone tools they produced. One of the perhaps most
      spectacular re-inventions of that time is heat treatment of stones prior to their
      manufacture into tools. Although heat treatment has been understood as one of the
      defining characteristics of the Beuronian of southwestern Germany, and although
      its existence has been known for almost 30 years now, relatively few systematic
      studies on it are available. In this paper, we present such a study, aiming to
      shed light on two questions: (1) what technique and heating parameters were used
      in the Beuronian and (2) how reliable are the macroscopic proxies traditionally
      used to identify heat treatment in this context? We investigate these questions
      using a non-destructive archaeometric technique for measuring past heating
      temperatures of heat-treated stones and a quantitative surface roughness analysis
      aiming to understand the relations between surface aspect and heat treatment.
      These methods are applied to 46 Jurassic chert artefacts from the site Helga-Abri
      located in the Swabian Alb region of southwestern Germany. Our results document
      that an opportunistic low-investment procedure was used to heat stone, probably
      relying on the use of the above-ground part of regular camp-fires. We also found
      that the traditionally used macroscopic criteria, such as colour and surface
      gloss, cannot be unambiguously used to identify heat treatment in assemblages
      made from Jurassic chert. These findings have important implications for our
      understanding of the Beuronian lithic chaine operatoire in terms of the
      investment in time and resources necessary, and for the refinement of
      archaeological techniques used to identify heat treatment in the Mesolithic of
      the Swabian Alb.

PMID- 29211750
TI  - Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose
      intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a
      Brown Norway strain chromosome 1 congenic donor region.
AB  - Our objective is to identify genes that influence the development of any
      phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use
      the reproductively isolated UC Davis fatty Zucker strain rat model in which the
      defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty
      obesity. We previously produced a congenic strain with the distal half of
      chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background
      (BN.ZUC-D1Rat183-D1Rat90). Previously published studies in males showed that the
      BN congenic donor region protects from some phenotypes of renal dysfunction and
      T2D. We now expand our studies to include females and expand phenotyping to gene
      expression. We performed diabetes and kidney disease phenotyping in chow-fed
      females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific
      characteristics of the UC Davis model. Fatty LeprfaSte/faSte animals of both BN
      and ZUC genotype in the congenic donor region had prediabetic levels of fasting
      blood glucose and blood glucose 2 hours after a glucose tolerance test. We
      observed significant congenic strain chromosome 1 genotype effects of the BN
      donor region in fatty females that resulted in decreased food intake, urine
      volume, glucose area under the curve during glucose tolerance test, plasma
      triglyceride levels, and urine glucose excretion per day. In fatty females, there
      were significant congenic strain BN genotype effects on non-fasted plasma urea
      nitrogen, triglyceride, and creatinine. Congenic region genotype effects were
      observed by quantitative PCR of mRNA from the kidney for six genes, all located
      in the chromosome 1 BN donor region, with potential effects on T2D or kidney
      function. The results are consistent with the hypothesis that the BN genotype
      chromosome 1 congenic region influences traits of both type 2 diabetes and kidney
      function in fatty UC Davis ZUC females and that there are many positional
      candidate genes.

PMID- 29211752
TI  - Getting the full picture: Assessing the complementarity of citizen science and
      agency monitoring data.
AB  - While the role of citizen science in engaging the public and providing large
      scale datasets has been demonstrated, the nature of and potential for this
      science to supplement environmental monitoring efforts by government agencies has
      not yet been fully explored. To this end, the present study investigates the
      complementarity of a citizen science programme to agency monitoring of water
      quality. The Environment Agency (EA) is the governmental public body responsible
      for, among other duties, managing and monitoring water quality and water
      resources in England. FreshWater Watch (FWW) is a global citizen science project
      that supports community monitoring of freshwater quality. FWW and EA data were
      assessed for their spatio-temporal complementarity by comparing the geographical
      and seasonal coverage of nitrate (N-NO3) sampling across the River Thames
      catchment by the respective campaigns between spring 2013 and winter 2015. The
      analysis reveals that FWW citizen science-collected data complements EA data by
      filling in both gaps in the spatial and temporal coverage as well as gaps in
      waterbody type and size. In addition, partial spatio-temporal overlap in sampling
      efforts by the two actors is discovered, but EA sampling is found to be more
      consistent than FWW sampling. Statistical analyses indicate that regardless of
      broader geographical overlap in sampling effort, FWW sampling sites are
      associated with a lower stream order and water bodies of smaller surface areas
      than EA sampling sites. FWW also samples more still-water body sites than the EA.
      As a possible result of such differences in sampling tendencies, nitrate
      concentrations, a measure of water quality, are lower for FWW sites than EA
      sites. These findings strongly indicate that citizen science has clear potential
      to complement agency monitoring efforts by generating information on freshwater
      ecosystems that would otherwise be under reported.

PMID- 29211751
TI  - Diffusion tensor imaging detects ventilation-induced brain injury in preterm
      lambs.
AB  - PURPOSE: Injurious mechanical ventilation causes white matter (WM) injury in
      preterm infants through inflammatory and haemodynamic pathways. The relative
      contribution of each of these pathways is not known. We hypothesised that in vivo
      magnetic resonance imaging (MRI) can detect WM brain injury resulting from
      mechanical ventilation 24 h after preterm delivery. Further we hypothesised that
      the combination of inflammatory and haemodynamic pathways, induced by umbilical
      cord occlusion (UCO) increases brain injury at 24 h. METHODS: Fetuses at 124+/-2
      days gestation were exposed, instrumented and either ventilated for 15 min using
      a high tidal-volume (VT) injurious strategy with the umbilical cord intact (INJ;
      inflammatory pathway only), or occluded (INJ+UCO; inflammatory and haemodynamic
      pathway). The ventilation groups were compared to lambs that underwent surgery
      but were not ventilated (Sham), and lambs that did not undergo surgery
      (unoperated control; Cont). Fetuses were placed back in utero after the 15 min
      intervention and ewes recovered. Twenty-four hours later, lambs were delivered,
      placed on a protective ventilation strategy, and underwent MRI of the brain using
      structural, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy
      (MRS) techniques. RESULTS: Absolute MRS concentrations of creatine and choline
      were significantly decreased in INJ+UCO compared to Cont lambs (P = 0.03, P =
      0.009, respectively); no significant differences were detected between the INJ or
      Sham groups and the Cont group. Axial diffusivities in the internal capsule and
      frontal WM were lower in INJ and INJ+UCO compared to Cont lambs (P = 0.05, P =
      0.04, respectively). Lambs in the INJ and INJ+UCO groups had lower mean
      diffusivities in the frontal WM compared to Cont group (P = 0.04). DTI colour
      mapping revealed lower diffusivity in specific WM regions in the Sham, INJ, and
      INJ+UCO groups compared to the Cont group, but the differences did not reach
      significance. INJ+UCO lambs more likely to exhibit lower WM diffusivity than INJ
      lambs. CONCLUSIONS: Twenty-four hours after injurious ventilation, DTI and MRS
      showed increased brain injury in the injuriously ventilated lambs compared to
      controls. DTI colour mapping threshold approach provides evidence that the
      haemodynamic and inflammatory pathways have additive effects on the progression
      of brain injury compared to the inflammatory pathway alone.

PMID- 29211753
TI  - Response of pumas (Puma concolor) to migration of their primary prey in
      Patagonia.
AB  - Large-scale ungulate migrations result in changes in prey availability for top
      predators and, as a consequence, can alter predator behavior. Migration may
      include entire populations of prey species, but often prey populations exhibit
      partial migration with some individuals remaining resident and others migrating.
      Interactions of migratory prey and predators have been documented in North
      America and some other parts of the world, but are poorly studied in South
      America. We examined the response of pumas (Puma concolor) to seasonal migration
      of guanacos (Lama guanicoe) in La Payunia Reserve in northern Patagonia
      Argentina, which is the site of the longest known ungulate migration in South
      America. More than 15,000 guanacos migrate seasonally in this landscape, and some
      guanacos also are resident year-round. We hypothesized that pumas would respond
      to the guanaco migration by consuming more alternative prey rather than migrating
      with guanacos because of the territoriality of pumas and availability of
      alternative prey throughout the year at this site. To determine whether pumas
      moved seasonally with the guanacos, we conducted camera trapping in the summer
      and winter range of guanacos across both seasons and estimated density of pumas
      with spatial mark-resight (SMR) models. Also, we analyzed puma scats to assess
      changes in prey consumption in response to guanaco migration. Density estimates
      of pumas did not change significantly in the winter and summer range of guanacos
      when guanacos migrated to and from these areas, indicating that pumas do not
      follow the migration of guanacos. Pumas also did not consume more alternative
      native prey or livestock when guanaco availability was lower, but rather fed
      primarily on guanacos and some alternative prey during all seasons. Alternative
      prey were most common in the diet during summer when guanacos also were abundant
      on the summer range. The response of pumas to the migration of guanacos differs
      from sites in the western North America where entire prey populations migrate and
      pumas migrate with their prey or switch to more abundant prey when their primary
      prey migrates.

PMID- 29211754
TI  - Testing the mindfulness-to-meaning theory: Evidence for mindful positive emotion
      regulation from a reanalysis of longitudinal data.
AB  - BACKGROUND AND OBJECTIVE: The Mindfulness to Meaning Theory (MMT) provides a
      detailed process model of mindful positive emotion regulation. DESIGN: We
      conducted a post-hoc reanalysis of longitudinal data (N = 107) derived from a RCT
      of mindfulness-based stress reduction (MBSR) versus cognitive-behavioral therapy
      (CBT) for social anxiety disorder to model the core constructs of the MMT
      (attentional control, decentering, broadened awareness, reappraisal, and positive
      affect) in a multivariate path analysis. RESULTS: Findings indicated that
      increases in attentional control from baseline to post-training predicted
      increases in decentering by 3 months post-treatment (p<.01) that in turn
      predicted increases in broadened awareness of interoceptive and exteroceptive
      data by 6 months post-treatment (p<.001). In turn, broadened awareness predicted
      increases in the use of reappraisal by 9 months post-treatment (p<.01), which
      culminated in greater positive affect at 12 months post-treatment (p<.001). MBSR
      led to significantly greater increases in decentering (p<.05) and broadened
      awareness than CBT (p<.05). Significant indirect effects indicated that increases
      in decentering mediated the effect of mindfulness training on broadening
      awareness, which in turn mediated enhanced reappraisal efficacy. CONCLUSION:
      Results suggest that the mechanisms of change identified by the MMT form an
      iterative chain that promotes long-term increases in positive affectivity. Though
      these mechanisms may reflect common therapeutic factors that cut across
      mindfulness-based and cognitive-behavioral interventions, MBSR specifically
      boosts the MMT cycle by producing significantly greater increases in decentering
      and broadened awareness than CBT, providing support for the foundational
      assumption in the MMT that mindfulness training may be a key means of stimulating
      downstream positive psychological processes.

PMID- 29211755
TI  - Comparison between the diagnostic validities of Xpert MTB/RIF and interferon
      gamma release assays for tuberculous pericarditis using pericardial tissue.
AB  - BACKGROUND: This study aimed to assess the diagnostic performance of Xpert
      MTB/RIF for tuberculous pericarditis (TBP) using pericardial tissues. METHODS:
      The study involved 30 patients admitted with suspected TBP from January-December
      2016; three patients were later excluded. The interferon-gamma release assay (T
      SPOT.TB) and the Xpert MTB/RIF test were performed using peripheral blood and
      pericardial tissues, respectively. TBP was confirmed using pericardial
      histopathology and a composite reference standard (CRS). We analyzed the
      sensitivity, specificity, predictive value (PV), likelihood ratio (LR), and area
      under curve (AUC) of both assays. RESULTS: Fourteen patients were confirmed as
      TBP, 10 as non-TBP, and 3 as probable TBP. The sensitivity, specificity, positive
      PV (PPV), negative PV (NPV), PLR, NLR, and AUC (95% confidence interval [CI]) of
      the Xpert MTB/RIF assay were 78.6% (49.2-95.3%) and 70.6% (44.0-89.7%); 92.3%
      (64.0-99.8%) and 100% (69.2-100%); 91.7% (61.5-99.8%) and 100% (73.5-100%); 80.0%
      (51.9-95.7%) and 66.7% (38.4-88.2%); 10.21 (1.52-68.49) and the PLR value was
      undefined with CRS as the reference; 0.23 (0.08-0.64) and 0.29(0.14-0.61); and
      0.854 (0.666-0.959) and 0.853 (0.664-0.959), against histopathology and CRS,
      respectively. The sensitivity, specificity, PPV, NPV, PLR, NLR, and AUC values
      (95% CI) of T-SPOT.TB were 92.9% (66.1-99.8%) and 94.1% (71.3-99.9%); 15.4% (1.9
      45.5%) and 20.0% (2.5-55.6%); 54.2% (32.8-74.5%) and 66.7% (44.7-84.4%); 66.7%
      (9.4-99.2%) and 66.7% (9.4-99.2%); 1.10 (0.83-1.44) and 1.18 (0.84-1.6); 0.46
      (0.05-4.53) and 0.29 (0.03-2.85); and 0.541(0.340-0.733) and 0.571(0.367-0.758),
      against histopathology and CRS, respectively. The differences in sensitivity,
      PPV, and AUC of Xpert MTB/RIF and T-SPOT.TB were not statistically significant (P
      > 0.05), compared to those of histopathology and CRS. However, the differences in
      specificity and NPV of the two assays were significant (P < 0.05), compared to
      those of histopathology and CRS. CONCLUSIONS: Xpert MTB/RIF test is a valid
      diagnostic technique for TBP with higher sensitivity and specificity than T
      SPOT.TB.

PMID- 29211756
TI  - Crystal structures of ternary complexes of archaeal B-family DNA polymerases.
AB  - Archaeal B-family polymerases drive biotechnology by accepting a wide substrate
      range of chemically modified nucleotides. By now no structural data for archaeal
      B-family DNA polymerases in a closed, ternary complex are available, which would
      be the basis for developing next generation nucleotides. We present the ternary
      crystal structures of KOD and 9 degrees N DNA polymerases complexed with DNA and
      the incoming dATP. The structures reveal a third metal ion in the active site,
      which was so far only observed for the eukaryotic B-family DNA polymerase delta
      and no other B-family DNA polymerase. The structures reveal a wide inner channel
      and numerous interactions with the template strand that provide space for
      modifications within the enzyme and may account for the high processivity,
      respectively. The crystal structures provide insights into the superiority over
      other DNA polymerases concerning the acceptance of modified nucleotides.

PMID- 29211758
TI  - Rubus: A compiler for seamless and extensible parallelism.
AB  - Nowadays, a typical processor may have multiple processing cores on a single
      chip. Furthermore, a special purpose processing unit called Graphic Processing
      Unit (GPU), originally designed for 2D/3D games, is now available for general
      purpose use in computers and mobile devices. However, the traditional programming
      languages which were designed to work with machines having single core CPUs,
      cannot utilize the parallelism available on multi-core processors efficiently.
      Therefore, to exploit the extraordinary processing power of multi-core
      processors, researchers are working on new tools and techniques to facilitate
      parallel programming. To this end, languages like CUDA and OpenCL have been
      introduced, which can be used to write code with parallelism. The main
      shortcoming of these languages is that programmer needs to specify all the
      complex details manually in order to parallelize the code across multiple cores.
      Therefore, the code written in these languages is difficult to understand, debug
      and maintain. Furthermore, to parallelize legacy code can require rewriting a
      significant portion of code in CUDA or OpenCL, which can consume significant time
      and resources. Thus, the amount of parallelism achieved is proportional to the
      skills of the programmer and the time spent in code optimizations. This paper
      proposes a new open source compiler, Rubus, to achieve seamless parallelism. The
      Rubus compiler relieves the programmer from manually specifying the low-level
      details. It analyses and transforms a sequential program into a parallel program
      automatically, without any user intervention. This achieves massive speedup and
      better utilization of the underlying hardware without a programmer's expertise in
      parallel programming. For five different benchmarks, on average a speedup of
      34.54 times has been achieved by Rubus as compared to Java on a basic GPU having
      only 96 cores. Whereas, for a matrix multiplication benchmark the average
      execution speedup of 84 times has been achieved by Rubus on the same GPU.
      Moreover, Rubus achieves this performance without drastically increasing the
      memory footprint of a program.

PMID- 29211757
TI  - Distinct fecal and oral microbiota composition in human type 1 diabetes, an
      observational study.
AB  - OBJECTIVE: Environmental factors driving the development of type 1 diabetes (T1D)
      are still largely unknown. Both animal and human studies have shown an
      association between altered fecal microbiota composition, impaired production of
      short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on
      SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy
      controls (HC) is lacking. RESEARCH DESIGN AND METHODS: We included 53 T1D
      patients without complications or medication and 50 HC matched for age, sex and
      BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of
      intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade
      systemic inflammation were measured. RESULTS: Oral microbiota were markedly
      different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis
      showed decreased butyrate producing species in T1D and less butyryl-CoA
      transferase genes. Also, plasma levels of acetate and propionate were lower in
      T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and
      Subdoligranulum correlated with glycemic control, inflammatory parameters and
      SCFA. CONCLUSIONS: We conclude that T1D patients harbor a different amount of
      intestinal SCFA (butyrate) producers and different plasma acetate and propionate
      levels. Future research should disentangle cause and effect and whether
      supplementation of SCFA-producing bacteria or SCFA alone can have disease
      modifying effects in T1D.

PMID- 29211759
TI  - Comparison of construct validity of two short forms of Stroke-Specific Quality of
      Life scale.
AB  - BACKGROUND: No studies have compared the 2-factor structures of Wong's and Post's
      versions of the short-form Stroke-Specific Quality of Life (i.e., 12-item SSQOL)
      scale. This study compared the construct validity of 2 short-forms of the 12-item
      SSQOL (not the 12-domain-SSQOL). METHODS: Data were obtained from a previous
      validation study of the original 49-item SSQOL in 263 patients. Construct
      validity was tested by confirmatory factor analysis (CFA) to examine whether the
      two-factor structure, including psychosocial and physical domains, was supported
      in both versions. The CFA tested the data-model fit by indices: chi-square
      chi2/df ratio, root mean square error of approximation (RMSEA), comparative fit
      index (CFI), nonnormative fit index (NNFI), standard root mean square residual
      (SRMR), and parsimony normed fit index (PNFI). Item factor loadings (cutoffs:
      .50) were examined. Model fit was compared using Akaike information criterion
      (AIC) and consistent AIC (i.e., CAIC) values. RESULTS: All model fit indices for
      Post's version fell within expected ranges: chi2/df ratio = 2.02, RMSEA = 0.05,
      CFI = 0.97, NNFI = 0.97, SRMR = 0.06, and PNFI = 0.76. In the psychosocial
      domain, the item factor loadings ranged from 0.46 to 0.63. In the physical
      domain, all items (except the language and vision items) had acceptable factor
      loadings (0.68 to 0.88). However, in Wong's version, none of the model indices
      met the criteria for good fit. In model fit comparisons, Post's version had
      smaller AIC and CAIC values than did Wong's version. CONCLUSIONS: All fit indices
      supported Post's version, but not Wong's version. The construct validity of
      Post's version with a 2-factor structure was confirmed, and this version of the
      12-item SSQOL is recommended.

PMID- 29211760
TI  - The serine protease homolog spheroide is involved in sensing of pathogenic Gram
      positive bacteria.
AB  - In Drosophila, recognition of pathogens such as Gram-positive bacteria and fungi
      triggers the activation of proteolytic cascades and the subsequent activation of
      the Toll pathway. This response can be achieved by either detection of pathogen
      associated molecular patterns or by sensing microbial proteolytic activities
      ("danger signals"). Previous data suggested that certain serine protease homologs
      (serine protease folds that lack an active catalytic triad) could be involved in
      the pathway. We generated a null mutant of the serine protease homolog spheroide
      (sphe). These mutant flies are susceptible to Enterococcus faecalis infection and
      unable to fully activate the Toll pathway. Sphe is required to activate the Toll
      pathway after challenge with pathogenic Gram-Positive bacteria. Sphe functions in
      the danger signal pathway, downstream or at the level of Persephone.

PMID- 29211761
TI  - Prophetic Granger Causality to infer gene regulatory networks.
AB  - We introduce a novel method called Prophetic Granger Causality (PGC) for
      inferring gene regulatory networks (GRNs) from protein-level time series data.
      The method uses an L1-penalized regression adaptation of Granger Causality to
      model protein levels as a function of time, stimuli, and other perturbations.
      When combined with a data-independent network prior, the framework outperformed
      all other methods submitted to the HPN-DREAM 8 breast cancer network inference
      challenge. Our investigations reveal that PGC provides complementary information
      to other approaches, raising the performance of ensemble learners, while on its
      own achieves moderate performance. Thus, PGC serves as a valuable new tool in the
      bioinformatics toolkit for analyzing temporal datasets. We investigate the
      general and cell-specific interactions predicted by our method and find several
      novel interactions, demonstrating the utility of the approach in charting new
      tumor wiring.

PMID- 29211762
TI  - RiboFACSeq: A new method for investigating metabolic and transport pathways in
      bacterial cells by combining a riboswitch-based sensor, fluorescence-activated
      cell sorting and next-generation sequencing.
AB  - The elucidation of the cellular processes involved in vitamin and cofactor
      biosynthesis is a challenging task. The conventional approaches to these
      investigations rely on the discovery and purification of the products (i.e
      proteins and metabolites) of a particular transport or biosynthetic pathway,
      prior to their subsequent analysis. However, the purification of low-abundance
      proteins or metabolites is a formidable undertaking that presents considerable
      technical challenges. As a solution, we present an alternative approach to such
      studies that circumvents the purification step. The proposed approach takes
      advantage of: (1) the molecular detection capabilities of a riboswitch-based
      sensor to detect the cellular levels of its cognate molecule, as a means to probe
      the integrity of the transport and biosynthetic pathways of the target molecule
      in cells, (2) the high-throughput screening ability of fluorescence-activated
      cell sorters to isolate cells in which only these specific pathways are
      disrupted, and (3) the ability of next-generation sequencing to quickly identify
      the genes of the FACS-sorted populations. This approach was named "RiboFACSeq".
      Following their identification by RiboFACSeq, the role of these genes in the
      presumed pathway needs to be verified through appropriate functional assays. To
      demonstrate the utility of our approach, an adenosylcobalamin (AdoCbl)-responsive
      riboswitch-based sensor was used in this study to demonstrate that RiboFACSeq can
      be used to track and sort cells carrying genetic mutations in known AdoCbl
      transport and biosynthesis genes with desirable sensitivity and specificity. This
      method could potentially be used to elucidate any pathway of interest, as long as
      a suitable riboswitch-based sensor can be created. We believe that RiboFACSeq
      would be especially useful for the elucidation of biological pathways in which
      the proteins and/or their metabolites are present at very low physiological
      concentrations in cells, as is the case with vitamin and cofactor biosynthesis.

PMID- 29211763
TI  - Hyperspectral imaging for simultaneous measurements of two FRET biosensors in
      pancreatic beta-cells.
AB  - Fluorescent protein (FP) biosensors based on Forster resonance energy transfer
      (FRET) are commonly used to study molecular processes in living cells. There are
      FP-FRET biosensors for many cellular molecules, but it remains difficult to
      perform simultaneous measurements of multiple biosensors. The overlapping
      emission spectra of the commonly used FPs, including CFP/YFP and GFP/RFP make
      dual FRET measurements challenging. In addition, a snapshot imaging modality is
      required for simultaneous imaging. The Image Mapping Spectrometer (IMS) is a
      snapshot hyperspectral imaging system that collects high resolution spectral data
      and can be used to overcome these challenges. We have previously demonstrated the
      IMS's capabilities for simultaneously imaging GFP and CFP/YFP-based biosensors in
      pancreatic beta-cells. Here, we demonstrate a further capability of the IMS to
      image simultaneously two FRET biosensors with a single excitation band, one for
      cAMP and the other for Caspase-3. We use these measurements to measure
      simultaneously cAMP signaling and Caspase-3 activation in pancreatic beta-cells
      during oxidative stress and hyperglycemia, which are essential components in the
      pathology of diabetes.

PMID- 29211764
TI  - Identification, expression and functional characterization of M4L, a muscarinic
      acetylcholine M4 receptor splice variant.
AB  - Rodent genomic alignment sequences support a 2-exon model for muscarinic M4
      receptor. Using this model a novel N-terminal extension was discovered in the
      human muscarinic acetylcholine M4 receptor. An open reading frame was discovered
      in the human, mouse and rat with a common ATG (methionine start codon) that
      extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by
      155 amino acids resulting in a longer variant. Transcriptional evidence for this
      splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from
      human donor brain prefrontal cortices. We detected a human upstream exon
      indicating the translation of the mature longer M4 receptor transcript. The
      predicted size for the longer two-exon M4 receptor splice variant with the
      additional 155 amino acid N-terminal extension, designated M4L is 69.7 kDa
      compared to the 53 kDa canonical single exon M4 receptor (M4S). Western blot
      analysis from a mammalian overexpression system, and saturation radioligand
      binding with [3H]-NMS (N-methyl-scopolamine) demonstrated the expression of this
      new splice variant. Comparative pharmacological characterization between the M4L
      and M4S receptors revealed that both the orthosteric and allosteric binding sites
      for both receptors were very similar despite the addition of an N-terminal
      extension.

PMID- 29211765
TI  - Impact of multisectoral health determinants on child mortality 1980-2010: An
      analysis by country baseline mortality.
AB  - INTRODUCTION: Some health determinants require relatively stronger health system
      capacity and socioeconomic development than others to impact child mortality. Few
      quantitative analyses have analyzed how the impact of health determinants varies
      by mortality level. METHODS: 149 low- and middle-income countries were stratified
      into high, moderate, low, and very low baseline levels of child mortality in
      1990. Data for 52 health determinants were collected for these countries for 1980
      2010. To quantify how changes in health determinants were associated with
      mortality decline, univariable and multivariable regression models were
      constructed. An advanced statistical technique that is new for child mortality
      analyses-MM-estimation with first differences and country clustering-controlled
      for outliers, fixed effects, and variation across decades. FINDINGS: Some health
      determinants (immunizations, education) were consistently associated with child
      mortality reduction across all mortality levels. Others (staff availability,
      skilled birth attendance, fertility, water and sanitation) were associated with
      child mortality reduction mainly in low or very low mortality settings. The
      findings indicate that the impact of some health determinants on child mortality
      was only apparent with stronger health systems, public infrastructure and levels
      of socioeconomic development, whereas the impact of other determinants was
      apparent at all stages of development. Multisectoral progress was essential to
      mortality reduction at all baseline mortality levels. CONCLUSION: Policy-makers
      can use such analyses to direct investments in health and non-health sectors and
      to set five-year child mortality targets appropriate for their baseline mortality
      levels and local context.

PMID- 29211766
TI  - Comparative analysis of the response and gene regulation in cold resistant and
      susceptible tea plants.
AB  - Cold environment is the main constraint for tea plants (Camellia sinensis)
      distribution and tea farming. We identified two tea cultivars, called var.
      sinensis cv. Shuchazao (SCZ) with a high cold-tolerance and var. assamica cv.
      Yinghong9 (YH9) with low cold-tolerance. To better understand the response
      mechanism of tea plants under cold stress for improving breeding, we compared
      physiological and biochemical responses, and associated genes expression in
      response to 7-day and 14-day cold acclimation, followed by 7-day de-acclimation
      in these two tea cultivars. We found that the low EL50, low Fv/Fm, and high
      sucrose and raffinose accumulation are responsible for higher cold tolerance in
      SCZ comparing with YH9. We then measured the expression of 14 key homologous
      genes, known as involved in these responses in other plants, for each stages of
      treatment in both cultivars using RT-qPCR. Our results suggested that the
      increased expression of CsCBF1 and CsDHNs coupling with the accumulation of
      sucrose play key roles in conferring higher cold resistance in SCZ. Our findings
      have revealed key genes regulation responsible for cold resistance, which help to
      understand the cold-resistant mechanisms and guide breeding in tea plants.

PMID- 29211767
TI  - Investigating endogenous u-opioid receptors in human keratinocytes as
      pharmacological targets using novel fluorescent ligand.
AB  - Opioids in skin function during stress response, regeneration, ageing and,
      particularly in regulating sensation. In chronic pruritus, topical treatment with
      Naltrexone changes MU-opioid receptor (MU-OR) localization to relieve itch. The
      molecular mechanisms behind the effects of Naltrexone on MU-OR function in
      reduction of itching behavior has not been studied. There is an immediate need to
      understand the endogenous complexity of MU-OR dynamics in normal and pathological
      skin conditions. Here we evaluate real-time behavior of MU-OR-Endomorphine
      complexes in the presence of agonist and antagonists. The MU-OR ligand
      Endomorphine-1 (EM) was conjugated to the fluorescent dye Tetramethylrhodamine
      (TAMRA) to investigate the effects of agonist and antagonists in N/TERT-1
      keratinocytes. The cellular localization of the EM-TAMRA was followed through
      time resolved confocal microscopy and population analysis was performed by flow
      cytometry. The in vitro analyses demonstrate fast internalization and trafficking
      of the endogenous EM-TAMRA-MU-OR interactions in a qualitative manner.
      Competition with Endomorphine-1, Naltrexone and CTOP show both canonical and non
      canonical effects in basal and differentiated keratinocytes. Acute and chronic
      treatment with Naltrexone and Endomorphine-1 increases EM-TAMRA binding to skin
      cells. Although Naltrexone is clinically effective in relieving itch, the
      mechanisms behind re-distribution of MU-ORs during clinical treatments are not
      known. Our study has given insight into cellular mechanisms of MU-OR ligand
      receptor interactions after opioid agonist and antagonist treatments in vitro.
      These findings potentially offer opportunities in using novel treatment
      strategies for skin and peripheral sensory disorders.

PMID- 29211768
TI  - High levels of tumor-associated neutrophils are associated with improved overall
      survival in patients with stage II colorectal cancer.
AB  - Conflicting reports regarding whether high tumor-associated neutrophils (TAN) are
      associated with outcomes in colorectal cancer (CRC) exist. Previous investigators
      have counted TAN using non-neutrophil-specific immunohistochemistry (IHC) stains.
      We examined whether TAN levels as determined by multi-field manual counting would
      predict prognosis. IRB approval was obtained and two pathologists, blinded to
      stage/outcome, counted TAN in 20 high power fields (HPF) per specimen. TAN score
      was defined as the mean of these counts. High TAN was defined as at or greater
      than the median score for that stage. Demographics, tumor characteristics, and
      overall survival (OS) were obtained from the records and examined for association
      with TAN score. IHC for arginase expression was performed in a subset of samples.
      221 patients were included. Stage II patients with high TAN scores had an OS of
      232 months as compared to those with low TAN (OS = 85 months, p = 0.03). The
      survival benefit persisted in multivariable analysis (HR 0.48, CI 0.25-0.91, p =
      0.026) controlling for age and sex. Women had increased survival as compared to
      men, and there were no significant prognostic associations with TAN count in
      stage III/IV patients, although there were only 12 stage IV patients. Arginase
      staining did not provide additional information. Stage II colorectal cancer
      patients with high TAN live nearly 3 times longer than those with low TAN. Women
      with stage II disease and high TAN counts appear to be driving the survival
      benefit seen in the stage II patients and have increased overall survival in all
      stages.

PMID- 29211769
TI  - Arsenic exposure and intestinal microbiota in children from Sirajdikhan,
      Bangladesh.
AB  - BACKGROUND: Arsenic has antimicrobial properties at high doses yet few studies
      have examined its effect on gut microbiota. This warrants investigation since
      arsenic exposure increases the risk of many diseases in which gut microbiota have
      been shown to play a role. We examined the association between arsenic exposure
      from drinking water and the composition of intestinal microbiota in children
      exposed to low and high arsenic levels during prenatal development and early
      life. RESULTS: 16S rRNA gene sequencing revealed that children with high arsenic
      exposure had a higher abundance of Proteobacteria in their stool compared to
      matched controls with low arsenic exposure. Furthermore, whole metagenome shotgun
      sequencing identified 332 bacterial SEED functions that were enriched in the high
      exposure group. A separate model showed that these genes, which included genes
      involved in virulence and multidrug resistance, were positively correlated with
      arsenic concentration within the group of children in the high arsenic group. We
      performed reference free genome assembly, and identified strains of E.coli as
      contributors to the arsenic enriched SEED functions. Further genome annotation of
      the E.coli genome revealed two strains containing two different arsenic
      resistance operons that are not present in the gut microbiome of a recently
      described European human cohort (Metagenomics of the Human Intestinal Tract,
      MetaHIT). We then performed quantification by qPCR of two arsenic resistant genes
      (ArsB, ArsC). We observed that the expression of these two operons was higher
      among the children with high arsenic exposure compared to matched controls.
      CONCLUSIONS: This preliminary study indicates that arsenic exposure early in life
      was associated with altered gut microbiota in Bangladeshi children. The
      enrichment of E.coli arsenic resistance genes in the high exposure group provides
      an insight into the possible mechanisms of how this toxic compound could affect
      gut microbiota.

PMID- 29211770
TI  - Socioeconomic differences in children's television viewing trajectory: A
      population-based prospective cohort study.
AB  - We aimed to evaluate the association between family socioeconomic status and
      repeatedly measured child television viewing time from early childhood to the
      school period. We analyzed data on 3,561 Dutch children from the Generation R
      Study, a population-based study in the Netherlands. Parent-reported television
      viewing time for children aged 2, 3, 4, 6 and 9 years were collected by
      questionnaires sent from April 2004 until January 2015. Odds ratios of watching
      television >=1 hour/day at each age were calculated for children of mothers with
      low, mid-low, mid-high and high (reference group) education and children from
      low, middle and high (reference group) income households. A generalized logistic
      mixed model was used to assess the association between family socioeconomic
      status and child television viewing time trajectory. The percentage of children
      watching television >=1 hour/day increased from age 2 to 9 years for all children
      (24.2%-85.0% for children of low-educated mothers; 4.7%-61.4% for children of
      high-educated mothers; 17.2%-74.9% for children from low income households; 6.2%
      65.1% for children from high income households). Independent socioeconomic effect
      in child television viewing time was found for maternal educational level. The
      interaction between net household income and child age in longitudinal analyses
      was significant (p = 0.01), indicating that the television viewing time
      trajectories were different in household income subgroups. However the
      interaction between maternal educational level and child age was not significant
      (p = 0.19). Inverse socioeconomic gradients in child television viewing time were
      found from the preschool period to the late school period. The educational
      differences between the various educational subgroups remained stable with
      increasing age, but the differences between household income groups changed over
      time. Intervention developers and healthcare practitioners need to raise
      awareness among non-highly educated parents that the socioeconomic gradient in
      television viewing time has a tracking effect starting from preschool age.

PMID- 29211772
TI  - Occupational endotoxin exposure in association with atopic sensitization and
      respiratory health in adults: Results of a 5-year follow-up.
AB  - The objective of the present longitudinal study was to investigate the effects of
      occupational endotoxin exposure on respiratory health and atopic sensitization in
      adults. Health outcomes and personal endotoxin exposure estimates were determined
      for 234 farmers and agricultural workers both at baseline and 5 years later. A
      questionnaire was used to assess respiratory symptoms, spirometry tests were
      performed and total and specific IgE levels were measured in serum. A twofold
      increase in personal endotoxin exposure was associated with less hay fever (OR
      0.68, 95%CI 0.54-0.87) and grass IgE positivity (OR 0.81, 95%CI 0.68-0.97) at
      both time points ("persistent" versus "never"). Although not statistically
      significant, a consistent protective pattern was observed for an increased loss
      of hay fever symptoms (OR 2.19, 95%CI 0.96-4.99) and grass IgE positivity (OR
      1.24, 95%CI 0.76-2.02), and for less new-onset of hay fever (OR 0.87, 95%CI 0.65
      1.17), grass IgE positivity (OR 0.83, 95%CI 0.61-1.12) and atopic sensitization
      (OR 0.75, 95%CI 0.55-1.02). Endotoxin exposure was not associated with changes in
      lung function. We showed that occupational endotoxin exposure is associated with
      a long-term protective effect on hay fever and grass IgE positivity. Results on
      longitudinal changes in hay fever, atopy and grass IgE positivity in adulthood
      were consistent with a protective effect of endotoxin exposure, but results need
      to be confirmed in larger cohorts. An effect of endotoxin exposure on lung
      function decline was not found.

PMID- 29211773
TI  - Design of a novel instrument for active neutron interrogation of artillery
      shells.
AB  - The most common explosives can be uniquely identified by measuring the elemental
      H/N ratio with a precision better than 10%. Monte Carlo simulations were used to
      design two variants of a new prompt gamma neutron activation instrument that can
      achieve this precision. The instrument features an intense pulsed neutron
      generator with precise timing. Measuring the hydrogen peak from the target
      explosive is especially challenging because the instrument itself contains
      hydrogen, which is needed for neutron moderation and shielding. By iterative
      design optimization, the fraction of the hydrogen peak counts coming from the
      explosive under interrogation increased from [Formula: see text]% to [Formula:
      see text]% (statistical only) for the benchmark design. In the optimized design
      variants, the hydrogen signal from a high-explosive shell can be measured to a
      statistics-only precision better than 1% in less than 30 minutes for an average
      neutron production yield of 109 n/s.

PMID- 29211771
TI  - Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS
      dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar
      ataxia type 1 (SCA1) mouse model.
AB  - Mitochondrial dysfunction plays a significant role in neurodegenerative disease
      including ataxias and other movement disorders, particularly those marked by
      progressive degeneration in the cerebellum. In this study, we investigate the
      role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar
      tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse.
      Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen
      consumption assays, we report that in the presence of mutant polyglutamine
      expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I
      (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of
      symptom onset and upregulation persists into late stage disease; yet, functional
      assembly of complex I macromolecules are diminished and oxygen respiration
      through complex I is reduced. Acute treatment of postsymptomatic SCA1 mice with
      succinic acid, a complex II (succinate dehydrogenase) electron donor to bypass
      complex I dysfunction, ameliorated cerebellar OXPHOS dysfunction, reduced
      cerebellar pathology and improved motor behavior. Thus, exploration of
      mitochondrial dysfunction and its role in neurodegenerative ataxias, and warrants
      further investigation.

PMID- 29211776
TI  - Correction: Genetic characterization of blaNDM-harboring plasmids in carbapenem
      resistant Escherichia coli from Myanmar.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184720.].

PMID- 29211775
TI  - Potential to curb the environmental burdens of American beef consumption using a
      novel plant-based beef substitute.
AB  - The food demands of the United States (US) impart significant environmental
      pressures. The high rate of consumption of beef has been shown to be the largest
      driver of food-borne greenhouse gas emissions, water use and land occupation in
      the US diet. The environmental benefits of substituting animal products with
      vegetal foods are well documented, but significant psychological barriers persist
      in reducing meat consumption. Here we use life cycle assessment to appraise the
      environmental performance of a novel vegetal protein source in the mean US diet
      where it replaces ground beef, and in vegetarian and vegan diets where it
      substitutes for legumes, tofu and other protein sources. We find that relative to
      the mean US diet, vegetarian and vegan diets significantly reduce per-capita food
      borne greenhouse gas emission (32% and 67%, respectively), blue water use (70%
      and 75%, respectively) and land occupation (70% and 79%, respectively), primarily
      in the form of rangeland. The substitution of 10%, 25% and 50% of ground beef
      with plant-based burger (PBB) at the national scale results in substantial
      reductions in annual US dietary greenhouse gas emissions (4.55-45.42 Mt CO2
      equivalents), water consumption (1.30-12.00 km3) and land occupation (22300
      190100 km2). Despite PBB's elevated environmental pressures compared to other
      vegetal protein sources, we demonstrate that minimal risk exists for the
      disservices of PBB substitution in non-meat diets to outweigh the benefits of
      ground-beef substitution in the omnivorous American diet. Demand for plant-based
      oils in PBB production has the potential to increase land use pressures in
      biodiversity hotspots, though these could be obviated through responsible land
      stewardship. Although the apparent environmental benefits of the PBB are
      contingent on actual uptake of the product, this study demonstrates the potential
      for non-traditional protein substitutes to play a role in a transition towards
      more sustainable consumption regimes in the US and potentially abroad.

PMID- 29211777
TI  - Alpha conotoxin-BuIA globular isomer is a competitive antagonist for oleoyl-L
      alpha-lysophosphatidic acid binding to LPAR6; A molecular dynamics study.
AB  - Lysophosphatidic acid receptor 6 (LPAR6) is a G-protein coupled receptor (GPCR)
      involved in hair development and cytoskeleton formation in mammals. Its
      proliferation is implicated in several forms of cancer including liver cancer,
      squamous cell carcinoma and metastatic prostate cancer. Current study emphasizes
      the isolation of competitive non-lipid and stable peptide antagonists for
      Lysophosphatidic acid ligand. A total of 148 conotoxin structures were
      characterized for their binding abilities against LPAR6. Subsequently, top 10
      conotoxins were selected on the basis of binding energy values, residual
      contributions and conformational cluster saturations. BuIA (a member of Alpha-
      conotoxins family), contryphan-R and contryphan-Lo (Synthetic class) conotoxins,
      exhibiting efficient binding parameters were subjected to molecular dynamics
      simulation assays and topology analysis. We propose that BuIA might be a potent
      antagonist due to its predominant binding at the extracellular region of LPAR6.
      Current study provides a backbone for understanding structural and functional
      insights of LPAR6 and findings of this study may be helpful in designing novel
      therapeutic targets for the treatment of cancers caused by elevated LPAR6
      expression.

PMID- 29211774
TI  - Food restriction reduces neurogenesis in the avian hippocampal formation.
AB  - The mammalian hippocampus is particularly vulnerable to chronic stress. Adult
      neurogenesis in the dentate gyrus is suppressed by chronic stress and by
      administration of glucocorticoid hormones. Post-natal and adult neurogenesis are
      present in the avian hippocampal formation as well, but much less is known about
      its sensitivity to chronic stressors. In this study, we investigate this question
      in a commercial bird model: the broiler breeder chicken. Commercial broiler
      breeders are food restricted during development to manipulate their growth curve
      and to avoid negative health outcomes, including obesity and poor reproductive
      performance. Beyond knowing that these chickens are healthier than fully-fed
      birds and that they have a high motivation to eat, little is known about how food
      restriction impacts the animals' physiology. Chickens were kept on a commercial
      food-restricted diet during the first 12 weeks of life, or released from this
      restriction by feeding them ad libitum from weeks 7-12 of life. To test the
      hypothesis that chronic food restriction decreases the production of new neurons
      (neurogenesis) in the hippocampal formation, the cell proliferation marker
      bromodeoxyuridine was injected one week prior to tissue collection.
      Corticosterone levels in blood plasma were elevated during food restriction, even
      though molecular markers of hypothalamic-pituitary-adrenal axis activation did
      not differ between the treatments. The density of new hippocampal neurons was
      significantly reduced in the food-restricted condition, as compared to chickens
      fed ad libitum, similar to findings in rats at a similar developmental stage.
      Food restriction did not affect hippocampal volume or the total number of
      neurons. These findings indicate that in birds, like in mammals, reduction in
      hippocampal neurogenesis is associated with chronically elevated corticosterone
      levels, and therefore potentially with chronic stress in general. This finding is
      consistent with the hypothesis that the response to stressors in the avian
      hippocampal formation is homologous to that of the mammalian hippocampus.

PMID- 29211778
TI  - Clinical global assessment of nutritional status as predictor of mortality in
      chronic kidney disease patients.
AB  - BACKGROUND: The value of subjective global assessment (SGA) as nutritional
      assessor of protein-energy wasting (PEWSGA) in chronic kidney disease (CKD)
      patients depends on its mortality predictive capacity. We investigated
      associations of PEWSGA with markers of nutritional status and all-cause mortality
      in CKD patients. METHODS: In 1031 (732 CKD1-5 non-dialysis and 299 dialysis)
      patients, SGA and body (BMI), lean (LBMI) and fat (FBMI) body mass indices, %
      handgrip strength (% HGS), serum albumin, and high sensitivity C-reactive protein
      (hsCRP) were examined at baseline. The five-year all-cause mortality predictive
      strength of baseline PEWSGA and during follow-up were investigated. RESULTS:
      PEWSGA was present in 2% of CKD1-2, 16% of CKD3-4, 31% of CKD5 non-dialysis and
      44% of dialysis patients. Patients with PEWSGA (n = 320; 31%) had higher hsCRP
      and lower BMI, LBMI, FBMI, %HGS and serum albumin. But, using receiver operating
      characteristics-derived cutoffs, these markers could not classify (by kappa
      statistic) or explain variations of (by multinomial logistic regression analysis)
      presence of PEWSGA. In generalized linear models, SGA independently predicted
      mortality after adjustments of multiple confounders (RR: 1.17; 95% CI: 1.11
      1.23). Among 323 CKD5 patients who were re-assessed after median 12.6 months, 222
      (69%) remained well-nourished, 37 (11%) developed PEWSGA de novo, 40 (12%)
      improved while 24 (8%) remained with PEWSGA. The latter independently predicted
      mortality (RR: 1.29; 95% CI: 1.13-1.46). CONCLUSIONS: SGA, a valid assessor of
      nutritional status, is an independent predictor of all-cause mortality both in
      CKD non-dialysis and dialysis patients that outperforms non-composite nutritional
      markers as prognosticator.

PMID- 29211779
TI  - Correction: Human alpha defensin 5 is a candidate biomarker to delineate
      inflammatory bowel disease.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179710.].

PMID- 29211780
TI  - Prevalence and antibiotic resistance of Pseudomonas aeruginosa in water samples
      in central Italy and molecular characterization of oprD in imipenem resistant
      isolates.
AB  - SCOPE: This study aimed to analyse the prevalence, antibiotic resistance and
      genetic relatedness of P. aeruginosa isolates obtained from potable and
      recreational water samples (n. 8,351) collected from different settings (swimming
      pools, n. 207; healthcare facilities, n 1,684; accommodation facilities, n.
      1,518; municipal waterworks, n. 4,500; residential buildings, n. 235). Possible
      mechanisms underlying resistance to imipenem, with particular focus on those
      involving oprD-based uptake, were also explored. METHODS AND RESULTS: Isolation
      and identification of Pseudomonas aeruginosa was performed according to the
      standardized procedure UNI EN ISO 16266:2008 followed by PCR confirmation.
      Antibiotic Susceptibility testing was conducted according to EUCAST standardized
      disk diffusion method. Genetic relatedness of strains was carried out by RAPD.
      The sequence of the oprD gene was analyzed by standard method. Fifty-three
      samples (0.63%) were positive for P. aeruginosa, of which 10/207 (4.83%) were
      from swimming pools. Five isolates (9.43%) were resistant to imipenem, one to
      Ticarcillin + Clavulanate, one to both Piperacillin and Ticarcillin +
      Clavulanate. The highest isolation rate of imipenem resistant P. aeruginosa was
      observed in swimming pool water. Identical RAPD profiles were found in isolates
      from the same location in the same year or even in different years. CONCLUSIONS:
      Imipenem resistant strains were identified as carbapenemase-negative and
      resistance has been associated with inactivating mutations within the oprD gene,
      with a concomitant loss of porin. RAPD results proved that a water system can
      remain colonized by one strain for long periods and the contamination may be
      difficult to eradicate. This study has revealed the presence of P. aeruginosa in
      different water samples, including resistant strains, especially in swimming
      pools, and confirmed the role of porins as a contributing factor in carbapenem
      resistance in Gram-negative bacteria.

PMID- 29211781
TI  - Blood pressure patterns and body mass index status in pregnancy: An assessment
      among women reporting for antenatal care at the Korle-Bu Teaching hospital,
      Ghana.
AB  - BACKGROUND: Maternal obesity in pregnancy has been linked with increased risk of
      pregnancy induced hypertension (PIH). In some tertiary referral hospitals in
      Ghana, PIH is the leading cause of institutional maternal mortality. OBJECTIVE:
      To evaluate blood pressure changes during pregnancy amongst different body mass
      index (BMI) groups and how this relates to the risk of developing PIH. METHODS:
      Women who had a dating ultrasound before 20 weeks gestation and registering for
      antenatal care at the Korle-Bu Teaching Hospital in Accra, between February and
      December 2013 and met the inclusion criteria were recruited into a cohort study.
      BMI was assessed at baseline. Blood pressure measurements were taken at (+/-2)
      24, 28 and 36 weeks. Primary outcome measure of interest during follow-up was a
      diagnosis of PIH at these points. BP changes during follow up at the three points
      were measured. Descriptive analysis of baseline factors was carried out and
      compared for the BMI groups. Relative risk (RR) of PIH was estimated at 95%
      confidence interval. RESULTS: Mean (SD) age for the 361 women was 30.9 (4.8)
      years. Incidence of PIH amongst the cohort was 10.5% (95% CI: 7.45% - 14.45%) and
      40.4% and 33.0% of them were overweight and obese respectively at baseline.
      Pregnant women who were obese at baseline had a three-fold increased risk of PIH
      compared to those with normal BMI [RR = 3.01 (1.06-8.52), p = 0.04]. CONCLUSION:
      Obese women have a significantly increased risk of PIH. Women should be screened
      at booking for obesity status. Antenatal protocols should have interventions for
      prevention or early detection of obesity and management of obesity to improve
      outcomes.

PMID- 29211782
TI  - Generative mathematical modelling to demonstrate virtual simulations of
      neovascular age related macular degeneration.
AB  - PURPOSE: To develop a generative mathematical model of wet age-related macular
      degeneration (AMD) and model the impact of injections of anti-vascular
      endothelial growth factor to virtual patients with the condition. METHODS: We
      isolated key pathophysiological components of macular degeneration in terms of
      macular edema development and response to anti-vascular endothelial growth factor
      (VEGF) agents. We developed mathematical models for each of these components
      using constants determined from published biological experimentation.
      Consequently, we combined the mathematical models of the separate components to
      arrive at an end-to-end model of the evolution of macular edema size and its
      response to treatment. RESULTS: We present a series of simulations based upon our
      idealised model. Initially, we demonstrate the theoretical change in macular
      edema height in wet macular degeneration over time without and with anti-VEGF
      interventions. In our final simulation, we demonstrate the powerful possibilities
      of virtual clinical trials by simulating a virtual model of a landmark study
      using our existing mathematical AMD model. CONCLUSIONS: Using our mathematical
      modelling based upon known pathological and pharmacological processes we have
      been able to model the effect of intravitreal injection of an anti-VEGF agent on
      macular edema from age related macular degeneration. We were subsequently able to
      mathematically simulate a major clinical trial with results that mirror many key
      features of the clinical established study. We anticipate that the generative
      model presented here can evolve to be a useful supportive tool in the challenge
      to deliver optimal therapy for patients with wet macular degeneration.

PMID- 29211783
TI  - Correction: Development of a real-time PCR for detection of Staphylococcus
      pseudintermedius using a novel automated comparison of whole-genome sequences.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183925.].

PMID- 29211784
TI  - Urinary metabolomic analysis to identify preterm neonates exposed to histological
      chorioamnionitis: A pilot study.
AB  - OBJECTIVE: Chorioamnionitis is a leading cause of preterm birth worldwide, with
      higher incidence at lower gestational ages. An early and reliable diagnosis of
      histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding
      postnatal management, especially the administration of prophylactic antibiotics
      to prevent early-onset sepsis. The main aim of this study was to investigate
      metabolomic analysis of urines collected in the first 24 hours of life as
      diagnostic tool of HCA. METHODS: Gestational age-, birth weight-, delivery mode-
      and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers
      with or without HCA were enrolled from an observational study. Gas chromatography
      mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine
      samples non-invasively collected in the first 24 hours of life. Univariate
      analysis, partial least square discriminant analysis (PLS-DA) and its associated
      variable importance in projection (VIP) score were performed. The most affected
      metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).
      RESULTS: Fifteen cases (mean GA 30.2 +/- 3.8 weeks, mean BW 1415 +/- 471.9 grams)
      and 30 controls (mean GA 30.2 +/- 2.9 weeks, mean BW 1426 +/- 569.8 grams) were
      enrolled. Following univariate analysis, 29 metabolites had a significantly
      different concentration between cases and controls. The supervised PLS-DA model
      confirmed a separation between the two groups. Only gluconic acid, an oxidation
      product of glucose, was higher in cases than in controls. All other VIP
      metabolites were more abundant in the control group. Glutamate metabolism,
      mitochondrial electron transport chain, citric acid cycle, galactose metabolism,
      and fructose and mannose degradation metabolism were the most significantly
      altered pathways (P < 0.01). CONCLUSIONS: For the first time, urinary
      metabolomics was able to discriminate neonates born to mothers with and without
      HCA. The identification of specifically altered metabolic pathways may be helpful
      in understanding metabolic derangement following chorioamnionitis.

PMID- 29211786
TI  - Pediatric siMS score: A new, simple and accurate continuous metabolic syndrome
      score for everyday use in pediatrics.
AB  - BACKGROUND: The dichotomous nature of the current definition of metabolic
      syndrome (MS) in youth results in loss of information. On the other hand, the
      calculation of continuous MS scores using standardized residuals in linear
      regression (Z scores) or factor scores of principal component analysis (PCA) is
      highly impractical for clinical use. Recently, a novel, easily calculated
      continuous MS score called siMS score was developed based on the IDF MS criteria
      for the adult population. OBJECTIVE: To develop a Pediatric siMS score (PsiMS), a
      modified continuous MS score for use in the obese youth, based on the original
      siMS score, while keeping the score as simple as possible and retaining high
      correlation with more complex scores. SUBJECTS AND METHODS: The database
      consisted of clinical data on 153 obese (BMI >=95th percentile) children and
      adolescents. Continuous MS scores were calculated using Z scores and PCA, as well
      as the original siMS score. Four variants of PsiMS score were developed in
      accordance with IDF criteria for MS in youth and correlation of these scores with
      PCA and Z score derived MS continuous scores was assessed. RESULTS: PsiMS score
      calculated using formula: (2xWaist/Height) + (Glucose(mmol/l)/5.6) +
      (triglycerides(mmol/l)/1.7) + (Systolic BP/130)-(HDL(mmol/l)/1.02) showed the
      highest correlation with most of the complex continuous scores (0.792-0.901). The
      original siMS score also showed high correlation with continuous MS scores.
      CONCLUSION: PsiMS score represents a practical and accurate score for the
      evaluation of MS in the obese youth. The original siMS score should be used when
      evaluating large cohorts consisting of both adults and children.

PMID- 29211785
TI  - The role of the clinical departments for understanding patient heterogeneity in
      one-year mortality after a diagnosis of heart failure: A multilevel analysis of
      individual heterogeneity for profiling provider outcomes.
AB  - PURPOSE: To evaluate the general contextual effect (GCE) of the hospital
      department on one-year mortality in Swedish and Danish patients with heart
      failure (HF) by applying a multilevel analysis of individual heterogeneity.
      METHODS: Using the Swedish patient register, we obtained data on 36,943 patients
      who were 45-80 years old and admitted for HF to the hospital between 2007 and
      2009. From the Danish Heart Failure Database (DHFD), we obtained data on 12,001
      patients with incident HF who were 18 years or older and treated at hospitals
      between June 2010 and June2013. For each year, we applied two-step single and
      multilevel logistic regression models. We evaluated the general effects of the
      department by quantifying the intra-class correlation coefficient (ICC) and the
      increment in the area under the receiver operating characteristic curve (AUC)
      obtained by adding the random effects of the department in a multilevel logistic
      regression analysis. RESULTS: One-year mortality for Danish incident HF patients
      was low in the three audit years (around 11.1% -13.1%) and departments performed
      homogeneously (ICC ~1.5% - 3.5%). The discriminatory accuracy of a model
      including age and gender was rather high (AUC~ 0.71-0.73) but the increment in
      AUC after adding the department random effects into these models was only about
      0.011-0.022 units in the three years. One-year mortality in Swedish patients with
      first hospitalization for heart failure, was relatively higher for 2007-2009
      (~21.3% - 22%) and departments performed homogeneously (ICC ~ 1.5% - 3%). The
      discriminatory accuracy of a model including age, gender and patient risk score
      was rather high (AUC~ 0.726-0.728) but the increment in AUC after adding the
      department random effects was only about 0.010-0.017 units in the three years.
      CONCLUSION: Using the DHFD standard benchmark for one-year mortality, Danish
      departments had a good, homogeneous performance. In reference to literature,
      Swedish departments had a homogeneous performance and the mortality rates for
      patients with first hospitalization for heart failure were similar to those
      reported since 2000. Considering this, if health authorities decide to further
      reduce mortality rates, a comprehensive quality strategy should focus on all
      Swedish hospitals. Yet, a complementary assessment for the period after the study
      period is required to confirm whether department performance is still homogeneous
      or not to determine the most appropriate action.

PMID- 29211787
TI  - The effect of somatostatin analogues on postoperative outcomes following
      pancreatic surgery: A meta-analysis.
AB  - BACKGROUND: Leakage from the pancreatic stump is a leading cause of morbidity
      following pancreatic surgery. It is essential to evaluate the effect of
      somatostatin analogues (SAs) following pancreatic surgery by analyzing all recent
      clinical trials. DATA SOURCES: We performed a literature search in the Medline,
      EMBASE, Cochrane Central Register of Controlled Trials and Web of Science
      databases up to May 29, 2016. Publication bias was assessed with Egger's test.
      Study quality was assessed using the Jadad Composite Scale. CONCLUSIONS: Twelve
      clinical trials involving 1703 patients from Jan 1st, 2000 to May 29th, 2016 were
      included in the study. With improvements in surgical management and peri
      operative patient care, prophylactic use of somatostatin and its analogues
      reduced the overall incidence of pancreatic fistulas (RR 0.72, 95% CI 0.55-0.94;
      p = 0.02) and decreased the post-operative hospital stay after pancreatic surgery
      (the weighted mean difference was -1.06, 95% CI-1/88 to -0.23; p = 0.01). Other
      post-operative outcomes did not change significantly with the use of somatostatin
      analogues.

PMID- 29211788
TI  - B-mode ultrasound assessment of pupillary function: Feasibility, reliability and
      normal values.
AB  - PURPOSE: To evaluate B-mode ultrasound as a novel method for the examination of
      pupillary function and to provide normal values for the pupillary reflex as
      assessed by B-mode ultrasound. METHODS: 100 subjects (49 female, 51 male, mean
      [range] age 51 [18-80 years]) with no history of ophthalmologic disease, no
      clinically detectable pupillary defects, and corrected visual acuity >= 0.8 were
      included in this prospective observational study. B-mode ultrasound was performed
      with the subjects eyes closed using an Esaote-Mylab25 system according to current
      guidelines for orbital insonation. A standardized light stimulus was applied.
      RESULTS: The mean +/- standard deviation left and right pupillary diameters (PD)
      at rest were 4.7 +/- 0.8 and 4.5 +/- 0.8 mm. Following an ipsilateral light
      stimulus (Lstim), left and right constricted PD were 2.8 +/- 0.6 and 2.7 +/- 0.6
      mm. Following a contralateral Lstim, left and right constricted PD were 2.7 +/-
      0.6 and 2.6 +/- 0.5 mm. Left and right pupillary constriction time (PCT)
      following ipsilateral Lstim were 970 +/- 261.6 and 967 +/- 220 ms. Left and right
      PCT following a contralateral Lstim were 993.8 +/- 192.6 and 963 +/- 189.4 ms.
      Patient age was inversely correlated with PD at rest and with PD after
      ipsilateral and contralateral Lstim (all p<0.001), but not with PCT. CONCLUSIONS:
      B-mode ultrasound is a simple, rapid and objective method for the quantitative
      assessment of pupillary function, which may prove useful in a variety of settings
      where eyelid retraction is impeded or an infrared pupillometry device is
      unavailable.

PMID- 29211789
TI  - Glycerol-3-phosphate acyltransferase 2 expression modulates cell roughness and
      membrane permeability: An atomic force microscopy study.
AB  - In mammalian cells, de novo glycerolipid synthesis begins with the acylation of
      glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferases (GPAT).
      GPAT2 is a mitochondrial isoform primarily expressed in testis under
      physiological conditions, and overexpressed in several types of cancers and
      cancer-derived human cell lines where its expression contributes to the tumor
      phenotype. Using gene silencing and atomic force microscopy, we studied the
      correlation between GPAT2 expression and cell surface topography, roughness and
      membrane permeability in MDA-MB-231 cells. In addition, we analyzed the
      glycerolipid composition by gas-liquid chromatography. GPAT2 expression altered
      the arachidonic acid content in glycerolipids, and the lack of GPAT2 seems to be
      partially compensated by the overexpression of another arachidonic-acid
      metabolizing enzyme, AGPAT11. GPAT2 expressing cells exhibited a rougher
      topography and less membrane damage than GPAT2 silenced cells. Pore-like
      structures were present only in GPAT2 subexpressing cells, correlating with
      higher membrane damage evidenced by lactate dehydrogenase release. These GPAT2
      induced changes are consistent with its proposed function as a tumor-promoting
      gene, and might be used as a phenotypic differentiation marker. AFM provides the
      basis for the identification and quantification of those changes, and
      demonstrates the utility of this technique in the study of cancer cell biology.

PMID- 29211790
TI  - Pericarpial nectary-visiting ants do not provide fruit protection against pre
      dispersal seed predators regardless of ant species composition and resource
      availability.
AB  - Extrafloral nectaries can occur in both vegetative and reproductive plant
      structures. In many Rubiaceae species in the Brazilian Cerrado, after corolla
      abscission, the floral nectary continues to secret nectar throughout fruit
      development originating post-floral pericarpial nectaries which commonly attract
      many ant species. The occurrence of such nectar secreting structures might be
      strategic for fruit protection against seed predators, as plants are expected to
      invest higher on more valuable and vulnerable parts. Here, we performed ant
      exclusion experiments to investigate whether the interaction with ants mediated
      by the pericarpial nectaries of Tocoyena formosa affects plant reproductive
      success by reducing the number of pre-dispersal seed predators. We also assessed
      whether ant protection was dependent on ant species composition and resource
      availability. Although most of the plants were visited by large and aggressive
      ant species, such as Ectatomma tuberculatum and species of the genus Camponotus,
      ants did not protect fruits against seed predators. Furthermore, the result of
      the interaction was neither related to ant species composition nor to the
      availability of resources. We suggest that these results may be related to the
      nature and behavior of the most important seed predators, like Hemicolpus
      abdominalis weevil which the exoskeleton toughness prevent it from being predated
      by most ant species. On the other hand, not explored factors, such as reward
      quality, local ant abundance, ant colony characteristics and/or the presence of
      alternative energetic sources could also account for variations in ant frequency,
      composition, and finally ant protective effects, highlighting the conditionality
      of facultative plant-ant mutualisms.

PMID- 29211791
TI  - Body size and hosts of Triatoma infestans populations affect the size of
      bloodmeal contents and female fecundity in rural northwestern Argentina.
AB  - Human sleeping quarters (domiciles) and chicken coops are key source habitats of
      Triatoma infestans-the principal vector of the infection that causes Chagas
      disease-in rural communities in northern Argentina. Here we investigated the
      links among individual bug bloodmeal contents (BMC, mg), female fecundity, body
      length (L, mm), host blood sources and habitats. We tested whether L, habitat and
      host blood conferred relative fitness advantages using generalized linear mixed
      effects models and a multimodel inference approach with model averaging. The data
      analyzed include 769 late-stage triatomines collected in 120 sites from six
      habitats in 87 houses in Figueroa, Santiago del Estero, during austral spring. L
      correlated positively with other body-size surrogates and was modified by habitat
      type, bug stage and recent feeding. Bugs from chicken coops were significantly
      larger than pig-corral and kitchen bugs. The best-fitting model of log BMC
      included habitat, a recent feeding, bug stage, log Lc (mean-centered log L) and
      all two-way interactions including log Lc. Human- and chicken-fed bugs had
      significantly larger BMC than bugs fed on other hosts whereas goat-fed bugs
      ranked last, in consistency with average blood-feeding rates. Fecundity was
      maximal in chicken-fed bugs from chicken coops, submaximal in human- and pig-fed
      bugs, and minimal in goat-fed bugs. This study is the first to reveal the
      allometric effects of body-size surrogates on BMC and female fecundity in a large
      set of triatomine populations occupying multiple habitats, and discloses the
      links between body size, microsite temperatures and various fitness components
      that affect the risks of transmission of Trypanosoma cruzi.

PMID- 29211792
TI  - The prognostic role of tumor size in early breast cancer in the era of molecular
      biology.
AB  - BACKGROUND: The prognosis of early breast cancer (EBC) depends on patient and
      tumor characteristics. The association between tumor size, the largest diameter
      in TNM staging, and prognosis is well recognized. According to TNM, tumors
      classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a
      volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even
      belonging to the same class. The aim of the study is to establish if the
      prognostic role of tumor size, expressed as diameter and volume, has been
      overshadowed by other factors. METHODS: The primary objective is to evaluate the
      association between tumor dimensions and overall survival (OS) / disease free
      survival (DFS), in our institution from January 1st 2005 to September 30th 2013
      in a surgical T1-T2 population. Volume was evaluated with the measurement of
      three half-diameters of the tumor (a, b and c), and calculated using the
      following formula: 4/3pi x a x b x c. RESULTS: 341 patients with T1-T2 EBC were
      included. 86.5% were treated with conservative surgery. 85.1% had a Luminal
      subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was
      942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died.
      With a median follow-up of 6.5 years, the univariate analysis for DFS showed an
      association between age, tumor size, volume, histological grading and molecular
      subtype. The multivariate analysis confirmed the statistically significant
      association only for molecular subtype (p 0.005), with a worse prognosis for
      Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65;
      95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate
      analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR:
      2.83; 95% CI:1.46-5.49; p 0.002). CONCLUSIONS: In our study, the only parameter
      that strongly influences survival is molecular subtype. These findings encourage
      clinicians to choose adjuvant treatment not based on dimensional criteria but on
      biological features.

PMID- 29211793
TI  - Assessing infection control practices to protect health care workers and patients
      in Malawi from nosocomial transmission of Mycobacterium tuberculosis.
AB  - Transmission of Mycobacterium tuberculosis (TB) in health settings threatens
      health care workers and people living with HIV in sub-Saharan Africa. Nosocomial
      transmission is reduced with implementation of infection control (IC) guidelines.
      The objective of this study is to describe implementation of TB IC measures in
      Malawi. We conducted a cross-sectional study utilizing anonymous health worker
      questionnaires, semi-structured interviews with facility managers, and direct
      observations at 17 facilities in central Malawi. Of 592 health care workers
      surveyed, 34% reported that all patients entering the facility were screened for
      cough and only 8% correctly named the four most common signs and symptoms of TB
      in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB
      screening questions for use in adults and children, respectively. Of 592 health
      workers, only 2.4% had been screened for TB in the previous year. Most (90%)
      reported knowing their HIV status, 53% were tested at their facility of
      employment, and half reported they would feel comfortable receiving ART or TB
      treatment at their facility of employment. We conclude that screening is
      infrequently conducted and knowledge gaps may undercut its effectiveness.
      Further, health care workers do not routinely access TB and HIV diagnostic and
      treatment services at their facility of employment.

PMID- 29211794
TI  - Correction: An Exact Expression to Calculate the Derivatives of Position
      Dependent Observables in Molecular Simulations with Flexible Constraints.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0024563.].

PMID- 29211795
TI  - Increase in salivary oxytocin and decrease in salivary cortisol after listening
      to relaxing slow-tempo and exciting fast-tempo music.
AB  - Relaxation and excitation are components of the effects of music listening. The
      tempo of music is often considered a critical factor when determining these
      effects: listening to slow-tempo and fast-tempo music elicits relaxation and
      excitation, respectively. However, the chemical bases that underlie these
      relaxation and excitation effects remain unclear. Since parasympathetic and
      sympathetic nerve activities are facilitated by oxytocin and glucocorticoid,
      respectively, we hypothesized that listening to relaxing slow-tempo and exciting
      fast-tempo music is accompanied by increases in the oxytocin and cortisol levels,
      respectively. We evaluated the change in the salivary oxytocin and cortisol
      levels of participants listening to slow-tempo and fast-tempo music sequences. We
      measured the heart rate (HR) and calculated the heart rate variability (HRV) to
      evaluate the strength of autonomic nerve activity. After listening to a music
      sequence, the participants rated their arousal and valence levels. We found that
      both the salivary oxytocin concentration and the high frequency component of the
      HRV (HF) increased and the HR decreased when a slow-tempo music sequence was
      presented. The salivary cortisol level decreased and the low frequency of the HRV
      (LF) to HF ratio (LF/HF) increased when a fast-tempo music sequence was
      presented. The ratio of the change in the oxytocin level was correlated with the
      change in HF, LF/HF and HR, whereas that in the cortisol level did not show any
      correlation with indices of autonomic nerve activity. There was no correlation
      between the change in oxytocin level and self-reported emotions, while the change
      in cortisol level correlated with the arousal level. These findings suggest that
      listening to slow-tempo and fast-tempo music is accompanied by an increase in the
      oxytocin level and a decrease in the cortisol level, respectively, and imply that
      such music listening-related changes in oxytocin and cortisol are involved in
      physiological relaxation and emotional excitation, respectively.

PMID- 29211797
TI  - Hooded seal Cystophora cristata foraging areas in the Northeast Atlantic Ocean
      Investigated using three complementary methods.
AB  - Identifying environmental characteristics that define the ecological niche of a
      species is essential to understanding how changes in physical conditions might
      affect its distribution and other aspects of its ecology. The present study used
      satellite relay data loggers (SRDLs) to study habitat use by Northeast Atlantic
      hooded seals (N = 20; 9 adult females, 3 adult males, and 8 juveniles). Three
      different methods were used in combination to achieve maximum insight regarding
      key foraging areas for hooded seals in this region, which have decline by 85% in
      recent decades: 1) first passage time (FPT); 2) vertical transit rate and; 3)
      change in dive drift rate. Generalized additive mixed models (GAMM) were applied
      to each method to determine whether specific habitat characteristics were
      associated with foraging. Separate models were run for the post-molting and the
      post-breeding seasons; sex and age classes were included in the GAMMs. All three
      methods highlighted a few common geographic areas as being important foraging
      zones; however, there were also some different areas identified by the different
      methods, which highlights the importance of using multiple indexes when analyzing
      tracking and diving data to study foraging behavior. Foraging occurred most
      commonly in relatively shallow areas with high Sea Surface Temperatures (SST),
      corresponding to continental shelf areas with Atlantic Water masses. All age and
      sex classes overlapped spatially to some extent, but the different age and sex
      groups showed differences in the bathymetry of their foraging areas as well as in
      their vertical use of the water column. When foraging, pups dove in the upper
      part of the water column in relatively deep areas. Adult females foraged
      relatively shallowly in deep water areas too, though in shallower areas than
      pups. Adult males foraged close to the bottom in shallower areas.

PMID- 29211796
TI  - Reprogramming pancreatic stellate cells via p53 activation: A putative target for
      pancreatic cancer therapy.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense
      fibrotic stroma, which contributes to tumor growth, metastasis, and drug
      resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are
      activated and become major contributors to fibrosis, by increasing growth factor
      signaling and extracellular matrix deposition. The p53 tumor suppressor is known
      to restrict tumor initiation and progression through cell autonomous mechanisms
      including apoptosis, cell cycle arrest, and senescence. There is growing evidence
      that stromal p53 also exerts anti-tumor activity by paracrine mechanisms, though
      a role for stromal p53 in PDAC has not yet been described. Here, we demonstrate
      that activation of stromal p53 exerts anti-tumor effects in PDAC. We show that
      primary cancer-associated PSCs (caPSCs) isolated from human PDAC express wild
      type p53, which can be activated by the Mdm2 antagonist Nutlin-3a. Our work
      reveals that p53 acts as a major regulator of PSC activation and as a modulator
      of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound
      transcriptional changes, which reprogram activated PSCs to quiescence. Using
      immunofluorescence and lipidomics, we have also found that p53 activation induces
      lipid droplet accumulation in both normal and tumor-associated fibroblasts,
      revealing a previously undescribed role for p53 in lipid storage. In vivo,
      treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces
      stromal p53 activation, reverses caPSCs activation, and decreases fibrosis. All
      together our work uncovers new functions for stromal p53 in PDAC.

PMID- 29211799
TI  - Comparison of miRNA quantitation by Nanostring in serum and plasma samples.
AB  - Circulating microRNAs that are associated with specific diseases have garnered
      much attention for use in diagnostic assays. However, detection of disease
      associated miRNA can be affected by several factors such as release of
      contaminating cellular miRNA during sample collection, variations due to
      amplification of transcript for detection, or controls used for normalization for
      accurate quantitation. We analyzed circulating miRNA in serum and plasma samples
      obtained concurrently from 28 patients, using a Nanostring quantitative assay
      platform. Total RNA concentration ranged from 32-125 MUg/ml from serum and 30-220
      MUg/ml from plasma. Of 798 miRNAs, 371 miRNAs were not detected in either serum
      or plasma samples. 427 were detected in either serum or plasma but not both,
      whereas 151 miRNA were detected in both serum and plasma samples. The diversity
      of miRNA detected was greater in plasma than in serum samples. In serum samples,
      the number of detected miRNA ranged from 3 to 82 with a median of 17, whereas in
      plasma samples, the number of miRNA detected ranged from 25 to 221 with a median
      of 91. Several miRNA such as miR451a, miR 16-5p, miR-223-3p, and mir25-3p were
      highly abundant and differentially expressed between serum and plasma. The
      detection of endogenous and exogenous control miRNAs varied in serum and plasma,
      with higher levels observed in plasma. Gene expression stability identified
      candidate invariant microRNA that were highly stable across all samples, and
      could be used for normalization. In conclusion, there are significant differences
      in both the number of miRNA detected and the amount of miRNA detected between
      serum and plasma. Normalization using miRNA with constant expression is essential
      to minimize the impact of technical variations. Given the challenges involved,
      ideal candidates for blood based biomarkers would be those that are indifferent
      to type of body fluid, are detectable and can be reliably quantitated.

PMID- 29211798
TI  - LipL21 lipoprotein binding to peptidoglycan enables Leptospira interrogans to
      escape NOD1 and NOD2 recognition.
AB  - Leptospirosis is a widespread zoonosis, potentially severe in humans, caused by
      spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense
      mechanisms involved in leptospirosis are poorly understood. Recognition of
      lipopolysaccharide (LPS) and lipoproteins by Toll-Like Receptors (TLR)4 and TLR2
      is crucial for clearance of leptospires in mice, yet the role of Nucleotide
      Oligomerization Domain (NOD)-like receptors (NOD)1 and NOD2, recognizing
      peptidoglycan (PG) fragments has not previously been examined. Here, we show that
      pathogenic leptospires escape from NOD1 and NOD2 recognition both in vitro and in
      vivo, in mice. We found that leptospiral PG is resistant to digestion by certain
      hydrolases and that a conserved outer membrane lipoprotein of unknown function,
      LipL21, specific for pathogenic leptospires, is tightly bound to the PG.
      Leptospiral PG prepared from a mutant not expressing LipL21 (lipl21-) was more
      readily digested than the parental or complemented strains. Muropeptides released
      from the PG of the lipl21- mutant, or prepared using a procedure to eliminate the
      LipL21 protein from the PG of the parental strain, were recognized in vitro by
      the human NOD1 (hNOD1) and NOD2 (hNOD2) receptors, suggesting that LipL21
      protects PG from degradation into muropeptides. LipL21 expressed in E. coli also
      resulted in impaired PG digestion and NOD signaling. We found that murine NOD1
      (mNOD1) did not recognize PG of L. interrogans. This result was confirmed by mass
      spectrometry showing that leptospiral PG was primarily composed of MurTriDAP, the
      natural agonist of hNOD1, and contained only trace amounts of the tetra
      muropeptide, the mNOD1 agonist. Finally, in transgenic mice expressing human NOD1
      and deficient for the murine NOD1, we showed enhanced clearance of a lipl21-
      mutant compared to the complemented strain, or to what was observed in NOD1KO
      mice, suggesting that LipL21 facilitates escape from immune surveillance in
      humans. These novel mechanisms allowing L. interrogans to escape recognition by
      the NOD receptors may be important in circumventing innate host responses.

PMID- 29211801
TI  - Correction: Assessment of municipal infrastructure development and its critical
      influencing factors in urban China: A FA and STIRPAT approach.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181917.].

PMID- 29211800
TI  - Diagnostic test strategies in children at increased risk of inflammatory bowel
      disease in primary care.
AB  - BACKGROUND: In children with symptoms suggestive of inflammatory bowel disease
      (IBD) who present in primary care, the optimal test strategy for identifying
      those who require specialist care is unclear. We evaluated the following three
      test strategies to determine which was optimal for referring children with
      suspected IBD to specialist care: 1) alarm symptoms alone, 2) alarm symptoms plus
      c-reactive protein, and 3) alarm symptoms plus fecal calprotectin. METHODS: A
      prospective cohort study was conducted, including children with chronic
      gastrointestinal symptoms referred to pediatric gastroenterology. Outcome was
      defined as IBD confirmed by endoscopy, or IBD ruled out by either endoscopy or
      unremarkable clinical 12 month follow-up with no indication for endoscopy. Test
      strategy probabilities were generated by logistic regression analyses and
      compared by area under the receiver operating characteristic curves (AUC) and
      decision curves. RESULTS: We included 90 children, of whom 17 (19%) had IBD (n =
      65 from primary care physicians, n = 25 from general pediatricians). Adding fecal
      calprotectin to alarm symptoms increased the AUC significantly from 0.80 (0.67
      0.92) to 0.97 (0.93-1.00), but adding c-reactive protein to alarm symptoms did
      not increase the AUC significantly (p > 0.05). Decision curves confirmed these
      patterns, showing that alarm symptoms combined with fecal calprotectin produced
      the diagnostic test strategy with the highest net benefit at reasonable threshold
      probabilities. CONCLUSION: In primary care, when children are identified as being
      at high risk for IBD, adding fecal calprotectin testing to alarm symptoms was the
      optimal strategy for improving risk stratification.

PMID- 29211802
TI  - Hidden alpha-helical propensity segments within disordered regions of the
      transcriptional activator CHOP.
AB  - C/EBP-homologous protein (CHOP) is a key determinant of the apoptotic response to
      endoplasmic reticulum stress or DNA damage. As a member of the C/EBP family, CHOP
      contains a low complexity N-terminal region involved in transcriptional
      activation, followed by a bZIP that binds DNA after dimerization. However, in
      contrast to other C/EBPs, CHOP directs binding to non-canonical C/EBP sites due
      to unique substitutions in its DNA-binding domain. Herein, we show that the N
      terminal region of CHOP is intrinsically unstructured but contains two segments
      presenting alpha-helical propensity. One of these segments is conserved in other
      C/EBPs and mediates essential roles of CHOP, including regulation through
      phosphorylation. The second segment is placed within a proteolytic-resistant
      portion of the protein and exhibits reduced flexibility. Moreover, the DNA
      binding region of CHOP also contains a segment with alpha-helical character
      towards its most N-terminal part. Our results suggest that structure-prone
      segments scattered within disordered regions may be critical for macromolecular
      recognition during CHOP-mediated transcriptional activation.

PMID- 29211803
TI  - Hypoxia and inactivity related physiological changes precede or take place in
      absence of significant rearrangements in bacterial community structure: The
      PlanHab randomized trial pilot study.
AB  - We explored the assembly of intestinal microbiota in healthy male participants
      during the randomized crossover design of run-in (5 day) and experimental phases
      (21-day normoxic bed rest (NBR), hypoxic bed rest (HBR) and hypoxic ambulation
      (HAmb) in a strictly controlled laboratory environment, with balanced fluid and
      dietary intakes, controlled circadian rhythm, microbial ambiental burden and 24/7
      medical surveillance. The fraction of inspired O2 (FiO2) and partial pressure of
      inspired O2 (PiO2) were 0.209 and 133.1 +/- 0.3 mmHg for NBR and 0.141 +/- 0.004
      and 90.0 +/- 0.4 mmHg for both hypoxic variants (HBR and HAmb; ~4000 m simulated
      altitude), respectively. A number of parameters linked to intestinal environment
      such as defecation frequency, intestinal electrical conductivity (IEC), sterol
      and polyphenol content and diversity, indole, aromaticity and spectral
      characteristics of dissolved organic matter (DOM) were measured (64 variables).
      The structure and diversity of bacterial microbial community was assessed using
      16S rRNA amplicon sequencing. Inactivity negatively affected frequency of
      defecation and in combination with hypoxia increased IEC (p < 0.05). In contrast,
      sterol and polyphenol diversity and content, various characteristics of DOM and
      aromatic compounds, the structure and diversity of bacterial microbial community
      were not significantly affected over time. A new in-house PlanHab database was
      established to integrate all measured variables on host physiology, diet,
      experiment, immune and metabolic markers (n = 231). The observed progressive
      decrease in defecation frequency and concomitant increase in IEC suggested that
      the transition from healthy physiological state towards the developed symptoms of
      low magnitude obesity-related syndromes was dose dependent on the extent of time
      spent in inactivity and preceded or took place in absence of significant
      rearrangements in bacterial microbial community. Species B. thetaiotamicron, B.
      fragilis, B. dorei and other Bacteroides with reported relevance for dysbiotic
      medical conditions were significantly enriched in HBR, characterized with most
      severe inflammation symptoms, indicating a shift towards host mucin degradation
      and proinflammatory immune crosstalk.

PMID- 29211804
TI  - The cardio-metabolic impact of taking commonly prescribed analgesic drugs in
      133,401 UK Biobank participants.
AB  - OBJECTIVE: There has been a significant increase in the prescribing of medication
      for chronic non-cancer pain. In a UK population sample, we aimed to assess cardio
      metabolic (CM) health in those taking these chronic pain medications. METHODS:
      133,401 participants from the UK Biobank cohort were studied. BMI, waist cm and
      hypertension were compared between those on drugs prescribed for chronic pain and
      CM drugs to those on CM drugs only. Multiple confounders were controlled for.
      RESULTS: Those taking opiates and CM drugs had the worst CM health profile with a
      95%, 82% and 63% increased odds of reporting obesity, 'very high risk' waist
      circumference and hypertension, respectively (OR [95% CI] 1.95 [1.75-2.17], 1.82
      [1.63-2.03], 1.63 [1.45-1.84]), compared to those on CM drugs alone. Those taking
      neuropathic pain medications and CM drugs also demonstrate worse CM profile than
      those taking CM drugs only. CONCLUSIONS: The impact of medications for chronic
      pain and sleep upon CM health and obesity is of concern for these classes of
      drugs which have been recently labelled as dependency forming medications. The
      results from this cross sectional study warrants further investigation and adds
      further support to calls for these medications to be prescribed for shorter
      periods.

PMID- 29211805
TI  - Leaf herbivory imposes fitness costs mediated by hummingbird and insect
      pollinators.
AB  - Plant responses induced by herbivore damage can provide fitness benefits, but can
      also have important costs due to altered interactions with mutualist pollinators.
      We examined the effects of plant responses to herbivory in a hummingbird
      pollinated distylous shrub, Palicourea angustifolia. Through a series of field
      experiments we investigated whether damage from foliar herbivores leads to a
      reduction in fruit set, influences floral visitation, or alters floral traits
      that may influence pollinator preference or pollinator efficiency. Foliar
      herbivory by a generalist grasshopper led to reduced fruit set in branches that
      were directly damaged as well as in adjacent undamaged branches on the same
      plant. Furthermore, herbivory resulted in reduced floral visitation from two
      common hummingbird species and two bee species. An investigation into the
      potential mechanisms behind reduced floral visitation in induced plants showed
      that foliar herbivore damage resulted in shorter styles and lower nectar volumes.
      This reduction in style length could reduce pollen deposition between different
      floral morphs that is required for optimal pollination in a distylous plant. We
      did not detect any differences in the volatile blends released by damaged and
      undamaged branches, suggesting that foliar herbivore-induced changes in floral
      morphology and rewards, and not volatile blends, are the primary mechanism
      mediating changes in visitation. Our results provide novel mechanisms for how
      plant responses induced by foliar herbivores can lead to ecological costs.

PMID- 29211806
TI  - Screening and identification of key genes regulating fall dormancy in alfalfa
      leaves.
AB  - Fall dormancy (FD) determines the adaptation of an alfalfa variety and affects
      alfalfa production and quality. However, the molecular mechanism underlying FD
      remains poorly understood. Here, 44 genes regulating FD were identified by
      comparison of the transcriptomes from leaves of Maverick (fall-dormant alfalfa)
      and CUF101(non-fall-dormant), during FD and non-FD and were classified them
      depending on their function. The transcription of IAA-amino acid hydrolase ILR1
      like 1, abscisic acid receptor PYL8, and monogalactosyldiacylglycerol synthase-3
      in Maverick leaves was regulated by daylength and temperature, and the
      transcription of the abscisic acid receptor PYL8 was mainly affected by
      daylength. The changes in the expression of these genes and the abundance of
      their messenger RNA (mRNA) in Maverick leaves differed from those in CUF101
      leaves, as evidenced by the correlation analysis of their mRNA abundance profiles
      obtained from April to October. The present findings suggested that these genes
      are involved in regulating FD in alfalfa.

PMID- 29211807
TI  - Null diffusion-based enrichment for metabolomics data.
AB  - Metabolomics experiments identify metabolites whose abundance varies as the
      conditions under study change. Pathway enrichment tools help in the
      identification of key metabolic processes and in building a plausible biological
      explanation for these variations. Although several methods are available for
      pathway enrichment using experimental evidence, metabolomics does not yet have a
      comprehensive overview in a network layout at multiple molecular levels. We
      propose a novel pathway enrichment procedure for analysing summary metabolomics
      data based on sub-network analysis in a graph representation of a reference
      database. Relevant entries are extracted from the database according to
      statistical measures over a null diffusive process that accounts for network
      topology and pathway crosstalk. Entries are reported as a sub-pathway network,
      including not only pathways, but also modules, enzymes, reactions and possibly
      other compound candidates for further analyses. This provides a richer biological
      context, suitable for generating new study hypotheses and potential enzymatic
      targets. Using this method, we report results from cells depleted for an
      uncharacterised mitochondrial gene using GC and LC-MS data and employing KEGG as
      a knowledge base. Partial validation is provided with NMR-based tracking of 13C
      glucose labelling of these cells.

PMID- 29211808
TI  - Estimating dispersal rates of Steller sea lion (Eumetopias jubatus) mother-pup
      pairs from a natal rookery using mark-resight data.
AB  - To monitor population trends of Steller sea lions (Eumetopias jubatus) in Alaska,
      newborn pups are counted during aerial surveys. These surveys are scheduled to
      occur after the majority of pups are born, but before pups begin to spend
      significant time in the water. Some studies have reported dispersal of mother-pup
      pairs away from breeding beaches during the pupping season (July), which may
      influence survey results. Using a multistate mark-recapture model with state
      uncertainty, we estimated the amount of dispersal during the pupping season based
      on observations of permanently marked sea lions. Research was conducted at land
      based observation sites on Marmot Island, Alaska, between 2000 and 2013. Both
      marked adult females with dependent pups and marked pups were observed at two
      rookery beaches from May to July. Cumulative dispersal rates were minimal (< 1%)
      prior to the planned start of the aerial survey (23 June) and increased to 11.2%
      by the planned survey completion date (10 July). The increased cumulative
      dispersal rate during the remainder of the observation period (end of July)
      suggests potential bias in surveys that occur beyond 10 July, however surveys
      past this date are rare (< 10% between 1973 and 2016). As a result, movements of
      mother-pup pairs during the pupping season are not likely to influence aerial
      survey estimates.

PMID- 29211809
TI  - Down-regulation of the klf5-c-Myc interaction due to klf5 phosphorylation
      mediates resveratrol repressing the caveolin-1 transcription through the
      PI3K/PKD1/Akt pathway.
AB  - Resveratrol (RSV), a natural polyphenol, has been reported to produce effect on
      genes transcription in lipid metabolism. In this study, we aim to explore the
      novel mechanisms of RSV on the regulation of caveolin-1 (Cav-1) transcription.
      Via body weight, blood glucose, serum lipid, and liver pathology detection, we
      found that RSV decreased body weight, blood glucose and lipid accumulation in
      rats fed high-fat diet. Based on co-immunoprecipitation (Co-IP) and western
      blotting assay, we found that RSV up-regulated klf5 phosphorylation and decreased
      the interaction of klf5 with c-Myc, which were accompanied by down-regulation of
      Cav-1 expression in livers of rats fed with high-fat diet. Moreover, in HEK293
      cells, we observed RSV enhanced klf5 phosphorylation and separated the
      interaction of klf5 with c-Myc through inhibiting the activation of PI3K/PKD1/Akt
      pathway, which maybe promoted c-Myc binding to the promoter to inhibit Cav-1
      expression. The results of the present study demonstrated that RSV activated klf5
      phosphorylation by inhibiting PI3K/PKD1/Akt pathway, and then attenuated the
      interaction of klf5 with c-Myc, subsequently probably promoted the c-Myc binding
      to the promoter to repress Cav-1 expression.

PMID- 29211810
TI  - Heterogeneity in the development of proactive and reactive aggression in
      childhood: Common and specific genetic - environmental factors.
AB  - BACKGROUND: Few studies are grounded in a developmental framework to study
      proactive and reactive aggression. Furthermore, although distinctive correlates,
      predictors and outcomes have been highlighted, proactive and reactive aggression
      are substantially correlated. To our knowledge, no empirical study has examined
      the communality of genetic and environmental underpinning of the development of
      both subtypes of aggression. The current study investigated the communality and
      specificity of genetic-environmental factors related to heterogeneity in
      proactive and reactive aggression's development throughout childhood. METHODS:
      Participants were 223 monozygotic and 332 dizygotic pairs. Teacher reports of
      aggression were obtained at 6, 7, 9, 10 and 12 years of age. Joint development of
      both phenotypes were analyzed through a multivariate latent growth curve model.
      Set point, differentiation, and genetic maturation/environmental modulation
      hypotheses were tested using a biometric decomposition of intercepts and slopes.
      RESULTS: Common genetic factors accounted for 64% of the total variation of
      proactive and reactive aggression's intercepts. Two other sets of uncorrelated
      genetic factors accounted for reactive aggression's intercept (17%) on the one
      hand, and for proactive (43%) and reactive (13%) aggression's slopes on the
      other. Common shared environmental factors were associated with proactive
      aggression's intercept (21%) and slope (26%) and uncorrelated shared
      environmental factors were also associated with reactive aggression's slope
      (14%). Common nonshared environmental factors explained most of the remaining
      variability of proactive and reactive aggression slopes. CONCLUSIONS: A genetic
      differentiation hypothesis common to both phenotypes was supported by common
      genetic factors associated with the developmental heterogeneity of proactive and
      reactive aggression in childhood. A genetic maturation hypothesis common to both
      phenotypes, albeit stronger for proactive aggression, was supported by common
      genetic factors associated with proactive and reactive aggression slopes. A
      shared environment set point hypothesis for proactive aggression was supported by
      shared environmental factors associated with proactive aggression baseline and
      slope. Although there are many common features to proactive and reactive
      aggression, the current research underscores the advantages of differentiating
      them when studying aggression.

PMID- 29211811
TI  - Challenges in the diagnosis of ulcerative colitis with concomitant bacterial
      infections and chronic infectious colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammation of the large bowel
      characterized by diarrhea and a negative stool culture. However, several
      enteropathogens have been implicated as causative agents in UC. The
      differentiation between chronic infectious colitis (IC) and UC with concurrent
      infection is difficult owing to their similar clinical presentations. The study
      aimed to explore the presentations and diagnostic clues that enable
      differentiation between UC with concomitant infections and chronic IC. The study
      included 17 UC patients with a bacterial infection and 46 with chronic IC. The UC
      patients (47 +/- 19 years) were younger than the chronic IC patients (58 +/- 20
      years) (P = 0.022). Bloody diarrhea was more common in UC than in chronic IC
      (58.8% vs 10.9%, P < 0.001). Previous antibiotic usage was a risk factor for
      chronic IC (5.9% vs 32.6%, P = 0.031). Malignancy was a common comorbidity of
      chronic IC (5.9% vs 34.8%, P = 0.022). UC patients had lower antibiotic response
      rates than chronic IC patients (60.0% vs 87.2%, P = 0.026). Aeromonas species and
      Clostridium difficile were common in both groups. Histological features of
      cryptitis and crypt abscess were useful in the diagnosis of UC (P = 0.052 and P =
      0.016, respectively). Bloody diarrhea in a young adult, decreased response to
      antibiotic treatment, and results of endoscopy with biopsy are important features
      in the diagnosis of UC with bacterial infection.

PMID- 29211812
TI  - A simulation study on the impact of the blood flow-dependent component in
      [18F]AV45 SUVR in Alzheimer's disease.
AB  - BACKGROUND: Increased brain uptake on [18F]AV45 PET is a biomarker for
      Alzheimer's disease (AD). The standardised uptake value ratio (SUVR) is widely
      used for quantification but is subject to variability. Here we evaluate how SUVR
      of a cortical target region is affected by blood flow changes in the target and
      two frequently used reference regions. METHODS: Regional baseline time-activity
      curves (TACs) were simulated based on metabolite-corrected plasma input functions
      and pharmacokinetic parameters obtained from our previously acquired data in
      healthy control (HC; n = 10), amnestic mild cognitive impairment (aMCI; n = 15)
      and AD cohorts (n = 9). Blood flow changes were simulated by altering the
      regional tracer delivery rate K1 (and clearance rate k2) between -40% and +40%
      from its regional baseline value in the target region and/or cerebellar grey (CB)
      or subcortical white matter (WM) reference regions. The corresponding change in
      SUVR was calculated at 50-60 min post-injection. RESULTS: A -40% blood flow
      reduction in the target resulted in an increased SUVRtarget (e.g. SUVRprecuneus:
      +10.0+/-5% in HC, +2.5+/-2% in AD), irrespective of the used reference region. A 
      40% blood flow reduction in the WM reference region increased SUVRWM (+11.5+/-4%
      in HC, +13.5+/-3% in AD) while a blood flow reduction in CB decreased SUVRCB (
      9.5+/-6% in HC, -5.5+/-2% in AD), irrespective of the used target region. A -40%
      flow reduction in both the precuneus and reference WM (i.e., global flow change)
      induced an increased SUVR (+22.5+/-8% in HC, +16.0+/-4% in AD). When considering
      reference CB instead, SUVR was decreased by less than -5% (both in HC and AD).
      CONCLUSION: Blood flow changes introduce alterations in [18F]AV45 PET SUVR. Flow
      reductions in the CB and WM reference regions resulted in a decreased and
      increased SUVR of the target, respectively. SUVR was more affected by global
      blood flow changes when considering WM instead of CB normalization.

PMID- 29211813
TI  - Scientometric study of the effects of exposure to non-ionizing electromagnetic
      fields on fertility: A contribution to understanding the reasons of partial
      failure.
AB  - The exposure to Non-Ionizing-Electromagnetic Fields (NI-EMFs) is often indicated
      as a cofactor responsible for the fertility reduction, which has been described
      in recent years. Despite the great interest in this topic and the research effort
      in exploring it, to date, there are no reliable data. Therefore, we carried out a
      scientometric analysis of the scientific literature published in peer reviewed
      Journals concerning this topic to better understand the reasons of this partial
      failure. To this aim, we identified and analysed 104 papers, published in last 26
      years in peer-reviewed Journals, present in ISI Web of Knowledge Core Collection.
      Then, we analysed the impact of the Journals in which the papers were published
      as well as that of the single papers, the paper citation dynamics, the keywords
      citation busts, the geographical localization of citations and the co-authorship
      dynamics of the Authors. As a result, we found that different animal models
      (rodent, rabbit, guinea pig, and swine) and different experimental approaches
      (epidemiological vs. experimental studies) have the same impact, highlighting the
      lack of universally adopted standard in research activity. The analysis of the
      temporal trend in keywords and the high differences in citations between the
      different countries (also in those belonging to the same geographical and socio
      economical area) pointed out the difficulties in approaching this branch of
      study. Lastly, it was evident that the Authors did not behave as a connected
      community, but as unconnected clusters of very small size. In conclusion, based
      on the results of our analysis, we think that important efforts must be
      undertaken to adopt more standardized models and to improve the research quality
      and the information exchange within the scientific community, with the aim of
      improving the reliability and usefulness of the results of research regarding the
      effect of NI-EMFs on fertility.

PMID- 29211814
TI  - Overexpression of transmembrane protein 168 in the mouse nucleus accumbens
      induces anxiety and sensorimotor gating deficit.
AB  - Transmembrane protein 168 (TMEM168) comprises 697 amino acid residues, including
      some putative transmembrane domains. It is reported that TMEM168 controls
      methamphetamine (METH) dependence in the nucleus accumbens (NAc) of mice.
      Moreover, a strong link between METH dependence-induced adaptive changes in the
      brain and mood disorders has been evaluated. In the present study, we
      investigated the effects of accumbal TMEM168 in a battery of behavioral
      paradigms. The adeno-associated virus (AAV) Tmem168 vector was injected into the
      NAc of C57BL/6J mice (NAc-TMEM mice). Subsequently, the accumbal TMEM168 mRNA was
      increased approximately by seven-fold when compared with the NAc-Mock mice
      (controls). The NAc-TMEM mice reported no change in the locomotor activity,
      cognitive ability, social interaction, and depression-like behaviors; however,
      TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark
      box test. The increased anxiety was reversed by pretreatment with the antianxiety
      drug diazepam (0.3 mg/kg i.p.). Moreover, the NAc-TMEM mice exhibited decreased
      prepulse inhibition (PPI) in the startle response test, and the induced
      schizophrenia-like behavior was reversed by pretreatment with the antipsychotic
      drug risperidone (0.01 mg/kg i.p.). Furthermore, accumbal TMEM168 overexpression
      decreased the basal levels of extracellular GABA in the NAc and the high K+ (100
      mM)-stimulated GABA elevation; however, the total contents of GABA in the NAc
      remained unaffected. These results suggest that the TMEM168-regulated GABAergic
      neuronal system in the NAc might become a novel target while studying the
      etiology of anxiety and sensorimotor gating deficits.

PMID- 29211816
TI  - Clinical outcome and molecular characterisation of chemorefractory metastatic
      colorectal cancer patients with long-term efficacy of regorafenib treatment.
AB  - Background: To investigate the potential predictors of response to regorafenib,
      in chemorefractory metastatic colorectal cancer (mCRC) patients with long-term
      efficacy from regorafenib treatment. Methods: Retrospective, single institution
      analysis of patients with chemorefractory mCRC treated with regorafenib, in
      clinical practice setting. 123 patients were treated and stratified into two
      groups according to number of cycles received (<7 and >=7). Overall survival
      (OS), progression-free survival (PFS) and safety were evaluated. 20 tumour
      samples (10 poor and 10 long responders) were analysed with the OncoMine
      Comprehensive Assay for 143 genes. Results: A good Eastern Cooperative Oncology
      Group performance status, a lung limited metastatic disease and a long history of
      metastatic disease were significantly associated with better OS and PFS from
      treatment with regorafenib. Mutations were mostly found in TP53, KRAS and PIK3CA
      as well as in NRAS, ERBB2, SMAD4 and PTEN genes. BCL2L1, ERBB2, KRAS, MYC, GAS6
      gene amplifications were detected as well as ALK rearrangement. No significant
      correlation between molecular alterations and response to regorafenib was
      observed. However, HER2 gene alterations were found in three poor responder
      patients, suggesting a potential role in regorafenib resistance. Conversely, GAS6
      amplification and SMAD4 mutation, detected in two long responder patients, might
      suggest a role of epithelial-mesenchymal transition phenotype in regorafenib
      response. Conclusion: A subgroup of long responder patients to regorafenib
      treatment was identified and a comprehensive molecular characterisation was
      performed; however, further research efforts are essential to confirm our data.

PMID- 29211815
TI  - Bacteria and bacterial envelope components enhance mammalian reovirus
      thermostability.
AB  - Enteric viruses encounter diverse environments as they migrate through the
      gastrointestinal tract to infect their hosts. The interaction of eukaryotic
      viruses with members of the host microbiota can greatly impact various aspects of
      virus biology, including the efficiency with which viruses can infect their
      hosts. Mammalian orthoreovirus, a human enteric virus that infects most humans
      during childhood, is negatively affected by antibiotic treatment prior to
      infection. However, it is not known how components of the host microbiota affect
      reovirus infectivity. In this study, we show that reovirus virions directly
      interact with Gram positive and Gram negative bacteria. Reovirus interaction with
      bacterial cells conveys enhanced virion thermostability that translates into
      enhanced attachment and infection of cells following an environmental insult.
      Enhanced virion thermostability was also conveyed by bacterial envelope
      components lipopolysaccharide (LPS) and peptidoglycan (PG). Lipoteichoic acid and
      N-acetylglucosamine-containing polysaccharides enhanced virion stability in a
      serotype-dependent manner. LPS and PG also enhanced the thermostability of an
      intermediate reovirus particle (ISVP) that is associated with primary infection
      in the gut. Although LPS and PG alter reovirus thermostability, these bacterial
      envelope components did not affect reovirus utilization of its proteinaceous
      cellular receptor junctional adhesion molecule-A or cell entry kinetics. LPS and
      PG also did not affect the overall number of reovirus capsid proteins sigma1 and
      sigma3, suggesting their effect on virion thermostability is not mediated through
      altering the overall number of major capsid proteins on the virus. Incubation of
      reovirus with LPS and PG did not significantly affect the neutralizing efficiency
      of reovirus-specific antibodies. These data suggest that bacteria enhance
      reovirus infection of the intestinal tract by enhancing the thermal stability of
      the reovirus particle at a variety of temperatures through interactions between
      the viral particle and bacterial envelope components.

PMID- 29211817
TI  - QTWiST analysis of the RECOURSE trial of trifluridine/tipiracil in metastatic
      colorectal cancer.
AB  - Purpose: A Quality-adjusted Time WIthout Symptoms of disease or Toxicity (QTWiST)
      analysis was carried out to assess quality-adjusted survival time in the RECOURSE
      trial of trifluridine/tipiracil versus placebo in pretreated metastatic
      colorectal cancer (mCRC). Methods: Duration of overall survival in the RECOURSE
      trial (n=798 patients) was partitioned into three discrete health states:
      toxicity (TOX), time without symptoms or toxicity (TWIST) and relapse (REL). TOX
      was defined as time spent with grade 3 or 4 treatment-related adverse events
      (AEs) after randomisation and before progression or censoring. AEs were limited
      to those related to trifluridine/tipiracil and known to affect quality of life
      (QoL) (ie, nausea, vomiting, diarrhoea, fatigue/asthaenia, anorexia and febrile
      neutropaenia). The estimated mean duration of each state, weighted by a utility
      coefficient representing QoL, was combined into a global QTWiST score. Results:
      In the RECOURSE trial, overall survival was 7.1 months with
      trifluridine/tipiracil versus 5.3 months with placebo. Patients receiving
      trifluridine/tipiracil spent longer in each health state than placebo recipients.
      Using assumed utility coefficients of 1 for TWIST and 0.5 for TOX and REL, the
      QTWiST was 5.48 months for the trifluridine/tipiracil group and 3.98 months for
      the placebo group, a difference of 1.5 (95% CI 1.49 to 1.52) months in favour of
      trifluridine/tipiracil. A sensitivity analysis using large variations in utility
      coefficients for TOX and REL produced a range of only approximately 0.5 months
      from minimum to maximum QTWiST. Conclusions: Quality-adjusted survival, as
      measured by QTWiST, shows clinically meaningful improvements in patients treated
      with trifluridine/tipiracil versus placebo in pretreated mCRC.

PMID- 29211818
TI  - Susceptibility to Alcohol Hangovers: Not Just a Matter of Being Resilient.
AB  - Introduction: Although most drinkers have experienced a hangover the day
      following heavy alcohol consumption, a minority claims to be hangover resistant
      despite consuming the same large quantities of alcohol as those reporting alcohol
      hangover. The aim of the current study was to examine if susceptibility to
      experiencing hangovers is related to a drinker's interpretation of wellbeing and
      psychological assets to bounce back. Methods: A survey was conducted among 2295
      Dutch students assessing their past month alcohol consumption patterns, and
      measuring mental resilience and wellbeing. Estimated peak blood alcohol
      concentration (e-pBAC) for their heaviest drinking occasion in the past month was
      computed for each participant. Data from participants who reported a past month
      hangover, i.e. hangover sensitive drinkers, were compared with hangover resistant
      drinkers. The analyses were conducted for (a) all participants reaching an e-pBAC
      >= 0.11% (N = 986, of which 24.6% claimed to be hangover resistant) and (b)
      participants reaching an e-pBAC >= 0.18% (N = 480, of which 16.7% claimed to be
      hangover resistant). Results: For both e-pBAC cut-off values, no significant
      differences between hangover sensitive and hangover resistant drinkers were found
      for mental resilience and wellbeing. Conclusion: The current findings suggest
      that having a hangover is not simply an expression of poor psychological coping
      with the next-day consequences of heavy alcohol consumption.

PMID- 29211819
TI  - Genomic Investigation of a Putative Endoscope-Associated Carbapenem-Resistant
      Enterobacter cloacae Outbreak Reveals a Wide Diversity of Circulating Strains and
      Resistance Mutations.
AB  - A genomic epidemiologic investigation of a putative carbapenem-resistant
      Enterobacter cloacae outbreak revealed few plausible instances of nosocomial
      transmission, highlighting instead the frequent importation of E. cloacae into
      our hospital. Searching for genetic determinants of carbapenem resistance
      demonstrated that most resistance is due to convergent mutations in
      phylogenetically diverse E. cloacae.

PMID- 29211820
TI  - Economic Impact of a Preferred Anti-Methicillin Susceptible Staphylococcus aureus
      Protocol.

PMID- 29211821
TI  - Elizabethkingia in Children: A Comprehensive Review of Symptomatic Cases Reported
      From 1944 to 2017.
AB  - Elizabethkingia species often exhibit extensive antibiotic resistance and result
      in high morbidity and mortality, yet no systematic reviews exist that thoroughly
      characterize and quantify concerns for infected infants and children. We
      performed a review of literature and identified an initial 902 articles; 96
      articles reporting 283 pediatric cases met our inclusion criteria and were
      subsequently reviewed. Case reports spanned 28 countries and ranged from 1944 to
      2017. Neonatal meningitis remains the most common presentation of this organism
      in children, along with a range of other clinical manifestations. The majority of
      reported cases occurred as isolated cases, rather than within outbreaks.
      Mortality was high but has decreased in recent years, although neurologic
      sequelae among survivors remains concerning. Child outcomes can be improved
      through effective prevention measures and early identification and treatment of
      infected patients.

PMID- 29211824
TI  - Corrigendum: Systematic reviews: guidance relevant for studies of older people.

PMID- 29211822
TI  - Insights from resolving protein-DNA interactions at near base-pair resolution.
AB  - One of the central goals in molecular biology is to understand how cell-type
      specific expression patterns arise through selective recruitment of RNA
      polymerase II (Pol II) to a subset of gene promoters. Pol II needs to be
      recruited to a precise genomic position at the proper time to produce messenger
      RNA from a DNA template. Ostensibly, transcription is a relatively simple
      cellular process; yet, experimentally measuring and then understanding the
      combinatorial possibilities of transcriptional regulators remain a daunting task.
      Since its introduction in 1985, chromatin immunoprecipitation (ChIP) has remained
      a key tool for investigating protein-DNA contacts in vivo. Over 30 years of
      intensive research using ChIP have provided numerous insights into mechanisms of
      gene regulation. As functional genomic technologies improve, they present new
      opportunities to address key biological questions. ChIP-exo is a refined version
      of ChIP-seq that significantly reduces background signal, while providing near
      base-pair mapping resolution for protein-DNA interactions. This review discusses
      the evolution of the ChIP assay over the years; the methodological differences
      between ChIP-seq, ChIP-exo and ChIP-nexus; and highlight new insights into
      epigenetic and transcriptional mechanisms that were uniquely enabled with the
      near base-pair resolution of ChIP-exo.

PMID- 29211823
TI  - Identifying functionally informative evolutionary sequence profiles.
AB  - Motivation: Multiple sequence alignments (MSAs) can provide essential input to
      many bioinformatics applications, including protein structure prediction and
      functional annotation. However, the optimal selection of sequences to obtain
      biologically informative MSAs for such purposes is poorly explored, and has
      traditionally been performed manually. Results: We present Selection of Alignment
      by Maximal Mutual Information (SAMMI), an automated, sequence-based approach to
      objectively select an optimal MSA from a large set of alternatives sampled from a
      general sequence database search. The hypothesis of this approach is that the
      mutual information among MSA columns will be maximal for those MSAs that contain
      the most diverse set possible of the most structurally and functionally
      homogeneous protein sequences. SAMMI was tested to select MSAs for functional
      site residue prediction by analysis of conservation patterns on a set of 435
      proteins obtained from protein-ligand (peptides, nucleic acids and small
      substrates) and protein-protein interaction databases. Availability and
      implementation: A freely accessible program, including source code, implementing
      SAMMI is available at https://github.com/nelsongil92/SAMMI.git. Contact:
      andras.fiser@einstein.yu.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29211826
TI  - Dose Suggestions for Intravenous Colistin in Pediatric Patients: Caution
      Required.

PMID- 29211825
TI  - Bicycle: a bioinformatics pipeline to analyze bisulfite sequencing data.
AB  - Summary: High-throughput sequencing of bisulfite-converted DNA is a technique
      used to measure DNA methylation levels. Although a considerable number of
      computational pipelines have been developed to analyze such data, none of them
      tackles all the peculiarities of the analysis together, revealing limitations
      that can force the user to manually perform additional steps needed for a
      complete processing of the data. This article presents bicycle, an integrated,
      flexible analysis pipeline for bisulfite sequencing data. Bicycle analyzes whole
      genome bisulfite sequencing data, targeted bisulfite sequencing data and
      hydroxymethylation data. To show how bicycle overtakes other available pipelines,
      we compared them on a defined number of features that are summarized in a table.
      We also tested bicycle with both simulated and real datasets, to show its level
      of performance, and compared it to different state-of-the-art methylation
      analysis pipelines. Availability and implementation: Bicycle is publicly
      available under GNU LGPL v3.0 license at http://www.sing-group.org/bicycle. Users
      can also download a customized Ubuntu LiveCD including bicycle and other
      bisulfite sequencing data pipelines compared here. In addition, a docker image
      with bicycle and its dependencies, which allows a straightforward use of bicycle
      in any platform (e.g. Linux, OS X or Windows), is also available. Contact:
      ograna@cnio.es or dgpena@uvigo.es. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29211827
TI  - Colistin Pharmacokinetics in Pediatrics.

PMID- 29211828
TI  - ASAR: visual analysis of metagenomes in R.
AB  - Motivation: Functional and taxonomic analyses are critical steps in understanding
      interspecific interactions within microbial communities. Currently, such analyses
      are run separately, which complicates interpretation of results. Here we present
      the ASAR interactive tool for simultaneous analysis of metagenomic data in three
      dimensions: taxonomy, function, metagenome. Results: An interactive data analysis
      tool for selection, aggregation and visualization of metagenomic data is
      presented. Functional analysis with a SEED hierarchy and pathway diagram based on
      KEGG orthology based upon MG-RAST annotation results is available. Availability
      and implementation: Source code of the ASAR is accessible at GitHub
      (https://github.com/Askarbek-orakov/ASAR). Contact: askarbek.orakov@nu.edu.kz or
      goryanin@gmail.com.

PMID- 29211829
TI  - Small RNA repertoires and their intraspecies variation in Aggregatibacter
      actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is a major periodontal pathogen that has
      several virulence factors such as leukotoxin and cytolethal distending toxin.
      Although the genes responsible for virulence have been identified, little is
      known about their regulatory mechanisms. Small RNA (sRNA) has been recognized as
      an important factor for gene regulation. To identify new regulatory mechanisms
      via sRNA in A. actinomycetemcomitans HK1651, we performed a systematic search for
      sRNAs by RNA-seq and identified 90 intergenic region sRNAs and 30 antisense
      sRNAs. Of the 85 analysable sRNAs, we successfully detected and quantified 70
      sRNAs by developing an RT-PCR system, and we identified 17 sRNAs that were
      differentially expressed during different growth phases. In addition, we found
      notable intraspecies variation in the sRNA repertoire of A.
      actinomycetemcomitans, thus suggesting that frequent acquisition or deletion of
      sRNAs occurred during the evolution of this species. The predicted target genes
      of the intergenic region sRNAs indicated the possibility of sRNA interaction with
      several virulence genes including leukotoxin and cytolethal distending toxin. Our
      results should serve as an important genomic and genetic basis for future studies
      to fully understand the regulatory network in A. actinomycetemcomitans and
      provide new insights into the intraspecies variation of the bacterial sRNA
      repertoire in bacteria.

PMID- 29211830
TI  - Antibiotic Utilization and the Role of Suspected and Diagnosed Mosquito-borne
      Illness Among Adults and Children With Acute Febrile Illness in Pune, India.
AB  - Background: Antibiotic resistance mechanisms originating in low- and middle-
      income countries are among the most common worldwide. Reducing unnecessary
      antibiotic use in India, the world's largest antibiotic consumer, is crucial to
      control antimicrobial resistance globally. Limited data describing factors
      influencing Indian clinicians to start or stop antibiotics are available.
      Methods: Febrile adults and children admitted to a public tertiary care hospital
      in Pune, India, were enrolled. Antibiotic usage and clinical history were
      recorded. Immunoassays for mosquito-borne disease and bacterial cultures were
      performed by protocol and clinician-directed testing. Clinical factors were
      assessed for association with empiric antibiotic initiation and discontinuation
      by day 5 using multivariable logistic regression and propensity score-matched Cox
      proportional hazard models. Results: Among 1486 participants, 683 (82%) adults
      and 614 (94%) children received empiric antibiotics. Participants suspected of
      having mosquito-borne disease were less likely to receive empiric antibiotics
      (adjusted odds ratio [AOR], 0.5; 95% confidence interval [CI], .4-.8). Empiric
      antibiotics were discontinued in 450 (35%) participants by day 5. Dengue or
      malaria testing performed before day 4 was positive in 162 (12%) participants,
      and was associated with antibiotic discontinuation (AOR, 1.7; 95% CI, 1.2-2.4).
      In a propensity score-matched model accounting for admission suspicion of
      mosquito-borne disease, positive dengue or malaria tests increased hazard of
      antibiotic discontinuation (hazard ratio, 1.6; 95% CI, 1.2-2.0). Conclusions:
      Most patients with acute febrile illness in an Indian public hospital setting
      receive empiric antibiotics. Mosquito-borne disease identification is associated
      with reduced empiric antibiotic use and faster antibiotic discontinuation.

PMID- 29211831
TI  - Towards Standardizing the Alcoholism Evaluation Of Potential Liver Transplant
      Recipients.
AB  - Aims: For teams around the world, alcoholic liver disease patients comprise the
      largest, and clinically most controversial, group applying for liver transplant.
      And yet evaluation decisions for them remain highly variable by locale. Methods:
      Targeting standardized assessment, we provide guidelines on what information the
      transplant team should seek, from what sources, and how best to make use of it.
      This report focuses on 'what to do and how to do it' in providing appropriate
      assessments for this complex patient group. Results: Proper evaluation includes
      (a) taking the clinical history from the patient and a required, corroborating
      third person, (b) assessing patient cognition, (c) establishing alcohol/substance
      use diagnosis to differentiate alcohol dependence, abuse and polysubstance
      dependence, (d) assessing ambivalence in primary alcohol addiction, (e) measuring
      social stability and (f) using Vaillant's factors for abstinence prognosis.
      Conclusions: Properly applied, these six factors will allow standardized
      selection in most cases taken across programs despite differences in resources,
      available expertise and decision practices. Short Summary: This report focuses on
      the essentials of the psychiatric/behavioral evaluation for 'alcoholic' persons
      referred for liver transplant. Attention to those essentials offers clinical
      standardization across transplant programs in different locales.

PMID- 29211832
TI  - Ultra-low input transcriptomics reveal the spore functional content and
      phylogenetic affiliations of poorly studied arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal fungi (AMF) are a group of soil microorganisms that
      establish symbioses with the vast majority of land plants. To date, generation of
      AMF coding information has been limited to model genera that grow well
      axenically; Rhizoglomus and Gigaspora. Meanwhile, data on the functional gene
      repertoire of most AMF families is non-existent. Here, we provide primary large
      scale transcriptome data from eight poorly studied AMF species (Acaulospora
      morrowiae, Diversispora versiforme, Scutellospora calospora, Racocetra castanea,
      Paraglomus brasilianum, Ambispora leptoticha, Claroideoglomus claroideum and
      Funneliformis mosseae) using ultra-low input ribonucleic acid (RNA)-seq
      approaches. Our analyses reveals that quiescent spores of many AMF species
      harbour a diverse functional diversity and solidify known evolutionary
      relationships within the group. Our findings demonstrate that RNA-seq data
      obtained from low-input RNA are reliable in comparison to conventional RNA-seq
      experiments. Thus, our methodology can potentially be used to deepen our
      understanding of fungal microbial function and phylogeny using minute amounts of
      RNA material.

PMID- 29211833
TI  - A prospective phase II study of combined androgen blockade in patients with
      androgen receptor-positive metastatic or locally advanced unresectable salivary
      gland carcinoma.
AB  - Background: There is no standard first-line chemotherapy for recurrent/metastatic
      (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).
      Patients and methods: We conducted a single institution, open-label, single arm,
      phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)
      positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of
      3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80
      mg. Patients were treated until progressive disease or unacceptable toxicities.
      Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM
      disease and three patients had LA disease. The pathological diagnoses were
      salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients,
      6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval
      (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%
      87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3
      months) and the median overall survival was 30.5 months (95% CI, 16.8 months to
      not reached). Additional analyses between treatment outcomes and
      clinicopathological factors or biomarkers including AR positivity, human
      epidermal growth factor receptor 2 status, and its complex downstream signaling
      pathway gene mutations showed no statistically significant differences. Elevated
      grade 3 liver transaminases and increased serum creatinine were reported in two
      patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide
      due to adverse event occurred in one patient. Conclusion: This study suggests
      that CAB has equivalent efficacy and less toxicity for patients with AR-positive
      RM or unresectable LA SGC compared with conventional chemotherapy, which warrants
      further study. Clinical Trial Registration: UMIN-CTR
      (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

PMID- 29211834
TI  - Long-term Therapeutic Impact of the Timing of Antiretroviral Therapy in Patients
      Diagnosed With Primary Human Immunodeficiency Virus Type 1 Infection.
AB  - Background: We aimed to determine the consequences of delayed human
      immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term
      outcomes depending on the time of combination antiretroviral therapy (cART)
      initiation in patients diagnosed during primary HIV infection (PHI). Methods: We
      selected patients from the French National Agency for Research on AIDS and Viral
      Hepatitis (ANRS) PRIMO cohort, treated for >=36 months, with sustained HIV RNA
      <50 copies/mL: 77 treated within 1 month following PHI diagnosis (immediate ART)
      and 73 treated >12 months after infection (deferred ART). We measured
      inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and
      CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit.
      Inflammation/activation levels were compared with those of uninfected controls.
      We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. Results: The
      decrease of HIV DNA levels was more marked in the immediate than deferred ART
      group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral
      blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and
      CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82
      months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio,
      ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term
      suppressive cART failed to normalize inflammation levels, which were not
      associated with immunovirological markers. Conclusions: Antiretroviral therapy
      initiated during PHI promotes long-term reduction of HIV reservoir size. In
      patients with sustained virologic suppression, inflammation may be driven by non
      HIV-related factors.

PMID- 29211836
TI  - Outbreak of Severe Histoplasmosis Among Tunnel Workers-Dominican Republic, 2015.
AB  - Background: Histoplasmosis is a fungal infection associated with exposure to bat
      guano. An outbreak of an unknown severe febrile illness occurred among tunnel
      workers in the Dominican Republic, and resulted in several deaths. We conducted
      an investigation to confirm etiology and recommend control measures. Methods: A
      case was defined as fever and >=2 symptoms consistent with histoplasmosis in a
      tunnel worker, July-September 2015. We interviewed workers and family members,
      reviewed medical records, tested serum and urine for Histoplasma
      antigen/antibody, and conducted a cohort study to identify risk factors for
      histoplasmosis and severe infection (intensive care). Results: A crew of 36 male
      workers removed large amounts of bat guano from tunnels without respiratory
      protection for a median of 24 days per worker (range, 1-25 days). Median age was
      32 years (range, 18-62 years); none were immunocompromised. Thirty (83%) workers
      had illness that met the case definition, of whom 28 (93%) were hospitalized, 9
      (30%) required intensive care, 6 (20%) required intubation, and 3 (10%) died. The
      median time from symptom onset to antifungal treatment was 6 days (range, 1-11
      days). Twenty-two of 34 (65%) workers had laboratory evidence of infection.
      Conclusions: Severe illnesses and death likely resulted from exposure to large
      inocula of Histoplasma capsulatum spores in an enclosed space, lack of
      respiratory protection, and delay in recognition and treatment. Clinician
      education about histoplasmosis, improved laboratory capacity to diagnose fungal
      infections, and occupational health guidance to protect workers against endemic
      fungi are recommended in the Dominican Republic.

PMID- 29211835
TI  - Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural
      Cambodia, 2014-2015.
AB  - Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed
      with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in
      Cambodia. A case-control study attributed the outbreak to unsafe injections. We
      aimed to reconstruct the likely transmission history of the outbreak. Methods: We
      assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus
      (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody
      (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and
      evolutionary phylogenetic analyses of viral strains. Geographical coordinates and
      parenteral exposure through medical services provided by an unlicensed healthcare
      practitioner were obtained from 193 cases and 1499 controls during interviews.
      Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79
      (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3
      sequences showed a 198-sample CRF01_AE strains cluster, with time to most recent
      common ancestor (tMRCA) in September 2013 (95% highest posterior density, August
      2012-July 2014), and a peak of 15 infections/day in September 2014. Three
      geospatial HIV hotspots were discernible in Roka and correlated with high
      exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases
      showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main
      clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e
      and tMRCAs in 2002-2003. Conclusions: Unsafe injections in Cambodia most likely
      led to an explosive iatrogenic spreading of HIV, associated with a long-standing
      and more genetically diverse HCV propagation.

PMID- 29211837
TI  - Effect of Ovarian Hormones and Mating Experience on the Preference of Female Mice
      to Investigate Male Urinary Pheromones.
AB  - In female mice, the expression of receptive lordosis behavior requires estradiol
      and progesterone actions in the nervous system; however, the contribution of
      these hormones to females' motivation to seek out male pheromones is less clear.
      In an initial experiment, sexually naive ovary-intact female mice preferred to
      investigate (make nasal contact with) testes-intact male as opposed to estrous
      female urine, provided they were in vaginal estrus. In a second experiment,
      groups of sexually naive and mating-experienced, ovariectomized females were
      tested for urinary pheromone preference first without and then with ovarian
      hormone replacement. Without hormone replacement, sexually naive ovariectomized
      females showed no preference for male over female urinary pheromones whereas
      mating-experienced females preferred to investigate male pheromones.
      Ovariectomized females in both groups preferred male over female urine after
      sequential s.c. injections with estradiol benzoate followed 2 days later with
      progesterone and after prolonged (7 days) exposure to estradiol alone. Our
      results indicate that in sexually naive female mice estradiol, perhaps aided by
      progesterone, is required to motivate a preference to seek out male pheromones
      whereas after mating experience females' preference to investigate male
      pheromones persists even in the absence of ovarian hormone action.

PMID- 29211838
TI  - The sensitivity of yeasts and yeasts-like fungi to copper and sulfur could
      explain lower yeast biodiversity in organic vineyards.
AB  - Although differences in yeast biodiversity have often been found between
      vineyards subjected to organic protection or conventional protection, little is
      known about the effect of copper and sulfur fungicides (the only fungicides
      allowed in organic farming) on yeast populations. The sensitivity to copper and
      sulfur of 158 yeast isolates of seven different species (Aureobasidium pullulans,
      Hanseniaspora guilliermondii, H. uvarum, Metschnikowia sp., Pichia
      membranifaciens, Saccharomyces cerevisiae and Starmerella bacillaris) was
      evaluated. The species A. pullulans and St. bacillaris appeared to be more
      resistant to copper than the other species tested. The species A. pullulans, H.
      guilliermondii and Metschnikowia sp. had the highest sulfur resistance. Thus,
      only isolates of the species A. pullulans exhibited high resistance to both
      antifungal agents. These results may explain the lower diversity of yeasts
      present on berries and the strong dominance of the species A. pullulans for
      vineyards protected by copper or sulfur-based fungicides compared to other
      vineyards reported by several studies.

PMID- 29211839
TI  - Genomic Loss and Silencing on the Y Chromosomes of Rumex.
AB  - Across many unrelated lineages of plants and animals, Y chromosomes show a
      recurrent pattern of gene degeneration and loss, but the relative importance of
      inefficient selection, adaptive gene silencing, and neutral genetic drift in
      causing degeneration remain poorly understood. Here, we use next-generation
      genome and transcriptome sequencing to investigate patterns of ongoing Y
      chromosome degeneration in two annual plant species of Rumex (Polygonaceae)
      differing in their degree of degeneration and sex chromosome heteromorphism. We
      find evidence for both gene loss as well as silencing in these young plant sex
      chromosomes. Our analyses revealed significantly more gene deletion relative to
      silencing in R. rothschildianus, which has had a larger nonrecombining region for
      a longer period than R. hastatulus, consistent with this system being at a more
      advanced stage of degeneration. Intra- and interspecific comparisons of genomic
      coverage and heterozygosity indicated that loss of expression precedes gene
      deletion, implying that the final stages of mutation accumulation and gene loss
      may often occur neutrally. We found no evidence for adaptive silencing of genes
      that have lost expression. Our results suggest that the initial spread of
      deleterious regulatory variants and/or epigenetic silencing may be an important
      driver of early degeneration of Y chromosomes.

PMID- 29211840
TI  - Occupational health risks and intervention strategies for US taxi drivers.
AB  - Research has shown that taxi drivers are at risk for numerous health concerns,
      such as low back and leg pain, linked to their highly sedentary occupation, long
      work hours and stressors related to the job (e.g. low income, safety threats).
      The goal of this study was to explore occupational health risks and opportunities
      for health interventions with taxi drivers using community-based participatory
      research (CBPR) methods. A mixed methods approach included first a convenience
      sample of 19 East African taxi drivers participating in focus group discussions.
      Second, a convenience sample of 75 current taxi drivers (M age = 45.7 years) and
      25 non-driver comparison participants (M age = 40.3 years) were recruited to
      complete a structured self-reported questionnaire and objective measures of
      health. Health education was provided alongside the research to address common
      health concerns and to ensure mutual benefit and an action orientation. The focus
      groups described numerous health concerns that drivers attributed to their
      occupation, including chronic pain, sleep deprivation, cardiovascular disease,
      diabetes, kidney disease and eye problems, as the most common. Participants
      offered ideas for health interventions that include workplace reform and driver
      education. Quantitative data indicate that 44% of drivers reported their health
      as 'fair' or 'poor'. Drivers were more likely to report musculoskeletal pain,
      less sleep, more fatigue and less physical activity as compared to non-drivers.
      The majority of drivers reported financial and job dissatisfaction. The research
      provides data to inform targeted health interventions that support the health and
      safety of taxi drivers.

PMID- 29211841
TI  - Perioperative benefit and outcome of thoracic epidural in esophageal surgery: a
      clinical review.
AB  - Surgery for esophageal cancer is a highly stressful and painful procedure, and a
      significant amount of analgesics may be required to eliminate perioperative pain
      and blunt the stress response to surgery. Proper management of postoperative pain
      has invariably been shown to reduce the incidence of postoperative complications
      and accelerate recovery. Neuraxial analgesic techniques after major thoracic and
      upper abdominal surgery have long been established to reduce respiratory,
      cardiovascular, metabolic, inflammatory, and neurohormonal complications.The aim
      of this review is to evaluate and discuss the relevant clinical benefits and
      outcome, as well as the possibilities and limits of thoracic epidural
      anesthesia/analgesia (TEA) in the setting of esophageal resections. A
      comprehensive search of original articles was conducted investigating relevant
      literature on MEDLINE, Cochrane reviews, Google Scholar, PubMed, and EMBASE from
      1985 to July2017. The relationship between TEA and important endpoints such as
      the quality of postoperative pain control, postoperative respiratory
      complications, surgical stress-induced immunosuppression, the overall
      postoperative morbidity, length of hospital stay, and major outcomes has been
      explored and reported. TEA has proven to enable patients to mobilize faster,
      cooperate comfortably with respiratory physiotherapists and achieve satisfactory
      postoperative lung functions more rapidly. The superior analgesia provided by
      thoracic epidurals compared to that from parenteral opioids may decrease the
      incidence of ineffective cough, atelectasis and pulmonary infections, while the
      associated sympathetic block has been shown to enhance bowel blood flow, prevent
      reductions in gastric conduit perfusion, and reduce the duration of ileus.
      Epidural anesthesia/analgesia is still commonly used for major 'open' esophageal
      surgery, and the recognized advantages in this setting are soundly established,
      in particular as regards the early recovery from anesthesia, the quality of
      postoperative pain control, and the significantly shorter duration of
      postoperative mechanical ventilation. However, this technique requires specific
      technical skills for an optimal conduction and is not devoid of risks,
      complications, and failures.

PMID- 29211843
TI  - Sexual activity in patients with left ventricular assist devices and their
      partners: impact of the device on quality of life, anxiety and depression.
AB  - OBJECTIVES: Prolonged support with a left ventricular assist device (LVAD) has
      evolved as an alternative treatment strategy for patients with end-stage heart
      disease. This requires a shift in focus on sexual activity and psychosocial
      outcomes in patients with an LVAD and their partners. METHODS: This cross
      sectional study was designed to capture Sexual Activities in Left Ventricular
      Assist Device Patients Or PaRtners (SALVADOR) perceptions on illness-related
      changes in the quality of sexual activity and its impact on quality of life,
      anxiety and depression using standardized patient-reported outcome scales (Sexual
      Adjustment Scale, 36-Item Short Form Health Survey, Hospital Anxiety and
      Depression Scale). A total of 72 patients with LVADs (50% response rate) along
      with 48 partners participated. RESULTS: For patients with an LVAD (median age 60
      years; 84.7% male), median time on the device was 650 days; 69.5% stayed in long
      term partnerships (median 23 years). Prevalence rates for illness-related changes
      in the quality of sexual activity were 58.3% for patients and 52.1% for partners.
      Device-related disturbances in sexual activities occurred due to battery pockets
      (patients/partners: 59.2%/37.6%; P = 0.006) and the driveline (46.3%/37.5%; P =
      0.033) and led to significantly increased distress in patients/partners (battery
      pockets: 53.5%/41.3%; P = 0.006; driveline 54.9%/37.5%; P = 0.004). Disturbances
      in sexual activity were independently associated with higher rates of depression
      (odds ratio 1.33, 95% confidence interval 1.14-1.55; P = 0.001) in patients and
      lower mental quality of life (odds ratio 6.18, 95% confidence interval 1.13
      33.98; P = 0.036) in partners. CONCLUSIONS: Disturbances in sexual activity are
      common in patients with an LVAD and their partners while the patients are on
      durable long-term support. Counselling on long-term adjustment should provide a
      platform for information seeking on illness-related changes in the quality of
      sexual activity.

PMID- 29211842
TI  - Maternal age at birth and daughters' subsequent childlessness.
AB  - STUDY QUESTION: Does maternal age at a daughter's birth predict her subsequent
      probability of lifelong childlessness? SUMMARY ANSWER: In this study population,
      women born to older mothers were more likely to be childless. WHAT IS KNOWN
      ALREADY: Although maternal age at childbearing is increasing in many countries,
      there is limited evidence on whether being born to older parents may influence
      offspring fertility. STUDY DESIGN SIZE AND DURATION: This analysis included 43
      135 women from the US-based Sister Study, a cohort study of 50 884 sisters of
      women with breast cancer recruited between 2003 and 2009. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Participants had no breast cancer at baseline. Women were
      included in the analytic sample if they were born between 1930 and 1964 and were
      at least 44 years old at enrolment. Median age when reproductive history was last
      ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of
      lifelong childlessness as a function of maternal age at birth, using
      multivariable log-binomial models, including total number of siblings, birth
      order, socioeconomic indicators of the family of origin, race and birth cohort.
      We examined the association in different subgroups and in a sibling-matched
      analysis including 802 sister pairs discordant for childlessness. MAIN RESULTS
      AND ROLE OF CHANCE: Compared with women born to 20-24-year-old mothers, those
      born to mothers aged 25-29, 30-34 and >=35 years were more likely to be childless
      [RR (95% CI): 1.21 (1.14-1.29), 1.30 (1.22-1.39) and 1.40 (1.31-1.50),
      respectively]. The association was consistent in strata defined by birth cohort,
      number of siblings, birth order, and participant's educational level, as well as
      within sister pairs. Overall, we found weak evidence for an independent
      contribution of paternal age at birth to the daughter's probability of
      childlessness. LIMITATIONS REASONS FOR CAUTION: All participants had at least one
      sister, and all information was self-reported. We had no knowledge of whether
      childlessness was intentional and found only a modest association between
      maternal age at birth and self-reported indicators of infertility. Still, the
      association with childlessness was highly consistent. WIDER IMPLICATIONS OF THE
      FINDING: Given the widespread tendency to delay childbearing, evaluating the
      influence of maternal age at birth on offspring fertility is a public health
      priority. STUDY FUNDING/COMPETING INTERESTS: This research was supported in part
      by the Intramural Research Programme of the NIH, National Institute of
      Environmental Health Sciences (Z01-ES044005). The authors report no conflict of
      interest.

PMID- 29211844
TI  - The association between asthma and type 1 diabetes: a paediatric case-cohort
      study in Finland, years 1981-2009.
AB  - Background: The association between asthma and type 1 diabetes, two chronic,
      immune-mediated diseases, has been of longstanding interest, but the evidence is
      still conflicting. We examined this association in a large, nationwide case
      cohort study among Finnish children, using a novel statistical approach. Methods:
      Among the initial cohort of all children born between 1 January 1981 and 31
      December 2008, those who were diagnosed with asthma (n = 81 473) or type 1
      diabetes (n = 9541) up to age 16 years by the end of 2009 were identified from
      the Central Drug Register maintained by the Social Insurance Institution of
      Finland. A 10% random sample from each initial birth year cohort was selected as
      a reference cohort (n = 171 138). The association between asthma and type 1
      diabetes was studied using a multistate modelling approach to estimate transition
      rates between healthy and disease states since birth. Hazard ratios (HRs) with
      95% confidence intervals (CIs) were calculated to represent the change in the
      transition rate between the disease states. Results: After adjusting for sex and
      birth decade, previous diagnosis of asthma increased the risk of subsequent type
      1 diabetes by 41% (95% CI: 1.28, 1.54), whereas previous diagnosis of type 1
      diabetes decreased the risk of subsequent asthma by 18% (95% CI: 0.69, 0.98).
      Conclusions: The findings of the present study imply that the association between
      the diseases is more complex than previously thought, and its direction depends
      on the sequential appearance of the diseases.

PMID- 29211845
TI  - Gene deletions leading to a reduction in the number of cyclopentane rings in
      Sulfolobus acidocaldarius tetraether lipids.
AB  - The cell membrane of (hyper)thermophilic archaea, including the thermoacidophile
      Sulfolobus acidocaldarius, incorporates dibiphytanylglycerol tetraether lipids.
      The hydrophobic cores of such tetraether lipids can include up to eight
      cyclopentane rings. Presently, nothing is known of the biosynthesis of these
      rings. In this study, a series of S. acidocaldarius mutants deleted of genes
      currently annotated as encoding proteins involved in sugar/polysaccharide
      processing were generated and their glycolipids were considered. Whereas the
      glycerol-dialkyl-glycerol tetraether core of a S. acidocaldarius tetraether
      glycolipid considered here mostly includes four cyclopentane rings, in cells
      where the Saci_0421 or Saci_1201 genes had been deleted, species containing zero,
      two or four cyclopentane rings were observed. At the same time, in cells lacking
      Saci_0201, Saci_0275, Saci_1101, Saci_1249 or Saci_1706, lipids containing mostly
      four cyclopentane rings were detected. Although Saci_0421 and Saci_1201 are not
      found in proximity to other genes putatively involved in lipid biosynthesis,
      homologs of these sequences exist in other Archaea containing cyclopentane
      containing tetraether lipids. Thus, Saci_0421 and Saci_1201 represent the first
      proteins described that somehow contribute to the appearance of cyclopentane
      rings in the core moiety of the S. acidocaldarius glycolipid considered here.

PMID- 29211846
TI  - SLC25A10 biallelic mutations in intractable epileptic encephalopathy with complex
      I deficiency.
AB  - Mitochondrial diseases are a plethora of inherited neuromuscular disorders
      sharing defects in mitochondrial respiration, but largely different from one
      another for genetic basis and pathogenic mechanism. Whole exome sequencing was
      performed in a familiar trio (trio-WES) with a child affected by severe epileptic
      encephalopathy associated with respiratory complex I deficiency and mitochondrial
      DNA depletion in skeletal muscle. By trio-WES we identified biallelic mutations
      in SLC25A10, a nuclear gene encoding a member of the mitochondrial carrier
      family. Genetic and functional analyses conducted on patient fibroblasts showed
      that SLC25A10 mutations are associated with reduction in RNA quantity and
      aberrant RNA splicing, and to absence of SLC25A10 protein and its transporting
      function. The yeast SLC25A10 ortholog knockout strain showed defects in
      mitochondrial respiration and mitochondrial DNA content, similarly to what
      observed in the patient skeletal muscle, and growth susceptibility to oxidative
      stress. Albeit patient fibroblasts were depleted in the main antioxidant
      molecules NADPH and glutathione, transport assays demonstrated that SLC25A10 is
      unable to transport glutathione. Here, we report the first recessive mutations of
      SLC25A10 associated to an inherited severe mitochondrial neurodegenerative
      disorder. We propose that SLC25A10 loss-of-function causes pathological
      disarrangements in respiratory-demanding conditions and oxidative stress
      vulnerability.

PMID- 29211848
TI  - Cloning and sequence analysis of 10-deacetylbaccatin III-10-O-acetyl transferase
      gene and WRKY1 transcription factor from taxol-producing endophytic fungus
      Lasiodiplodia theobromea.
AB  - In this study, we have isolated an endophytic fungal strain Lasiodiplodia
      theobromae from non-Taxus host plant Piper nigrum. The strain L. theobromae
      identity was confirmed by morphological characteristics and internal transcribed
      spacer sequence analysis. Taxol produced by L. theobromae was observed to be
      identical to the authentic taxol as analyzed by chromatography and spectroscopy
      methods. The quantity of taxol produced by the fungus was estimated to be 247 MUg
      L-1, and fungal taxol showed potent cytotoxic activity towards cancer cell line.
      Evidence to support the independent production of taxol by L. theobromea, the
      gene encoding 10-deacetylbacccation-III-O-acetyltransferase (DBAT), as well as,
      for the first time, open reading frame (ORF) of WRKY1 transcription factor (TF)
      were cloned and sequenced. The predicted amino sequence of L. theobromae dbat
      gene shared high homology with the taxol-producing plant and fungal dbat gene.
      Not only dbat gene, ORF of WRKY1 TF too shared high homology with Taxus chinensis
      WRKY1 TF ORF. To the best of our knowledge, this is the first report on cloning
      of dbat gene and its transcription factor from endophytes of non-Taxus host
      plant.

PMID- 29211849
TI  - Predictors of trimodality therapy and trends in therapy for malignant pleural
      mesothelioma.
AB  - OBJECTIVES: Malignant pleural mesothelioma is an aggressive and rare malignancy
      that frequently recurs despite aggressive therapy. We evaluated the frequency of
      treatment with surgery, radiation or chemotherapy, changes in therapy and
      survival over time and factors associated with the receipt of trimodality
      therapy. METHODS: The National Cancer Database (NCDB) was used to query patients
      with histologically proven malignant pleural mesothelioma (2004-14). Treatment
      over time was evaluated using the Armitage trend test. Factors associated with
      the receipt of trimodality therapy were analysed using logistic regression.
      RESULTS: Among 20 561 patients, only 4028 (20%) underwent cancer-directed
      surgery; 533 (2.6%) of whom received trimodality therapy. From 2004 to 2014, the
      use of surgery with chemotherapy increased 87% (P < 0.01), with no statistically
      significant change in the use of trimodality therapy. Median survival also
      increased from 8 months to 11 months (P < 0.01). Patients who were treated at an
      academic centre or who travel >26 miles for treatment were more likely to undergo
      trimodality therapy. Additional factors associated with the receipt of
      trimodality therapy include age less than 70, Charlson comorbidity score of 0 and
      presence of private insurance. CONCLUSIONS: Many malignant pleural mesothelioma
      patients are not treated with trimodality therapy, with significant variation in
      treatment patterns. Referrals to high-volume and specialized centres may help
      offer more therapeutic options and trial or registry enrolment.

PMID- 29211847
TI  - Changes in Neuronal Signaling and Cell Stress Response Pathways are Associated
      with a Multigenic Response of Drosophila melanogaster to DDT Selection.
AB  - The adaptation of insect populations to insecticidal control is a continual
      threat to human health and sustainable agricultural practices, but many complex
      genomic mechanisms involved in this adaption remain poorly understood. This study
      applied a systems approach to investigate the interconnections between structural
      and functional variance in response to dichlorodiphenyltrichloroethane (DDT)
      within the Drosophila melanogaster strain 91-R. Directional selection in 6
      selective sweeps coincided with constitutive gene expression differences in DDT
      resistant flies, including the most highly upregulated transcript, Unc-115 b,
      which plays a central role in axon guidance, and the most highly downregulated
      transcript, the angiopoietin-like CG31832, which is involved in directing
      vascular branching and dendrite outgrowth but likely may be under trans
      regulatory control. Direct functions and protein-protein interactions mediated by
      differentially expressed transcripts control changes in cell migration, signal
      transduction, and gene regulatory cascades that impact the nervous system.
      Although changes to cellular stress response pathways involve 8 different
      cytochrome P450s, stress response, and apoptosis is controlled by a multifacetted
      regulatory mechanism. These data demonstrate that DDT selection in 91-R may have
      resulted in genome-wide adaptations that impacts genetic and signal transduction
      pathways that converge to modify stress response, cell survival, and neurological
      functions. This study implicates the involvement of a multigenic mechanism in the
      adaptation to a chemical insecticide, which impact interconnected regulatory
      cascades. We propose that DDT selection within 91-R might act systemically,
      wherein pathway interactions function to reinforce the epistatic effects of
      individual adaptive changes on an additive or nonadditive basis.

PMID- 29211850
TI  - Sonic Hedgehog and WNT Signaling Promote Adrenal Gland Regeneration in Male Mice.
AB  - The atrophy and hypofunction of the adrenal cortex following long-term
      pharmacologic glucocorticoid therapy is a major health problem necessitating
      chronic glucocorticoid replacement that often prolongs the ultimate return of
      endogenous adrenocortical function. Underlying this functional recovery is
      anatomic regeneration, the cellular and molecular mechanisms of which are poorly
      understood. Investigating the lineage contribution of cortical Sonic hedgehog
      (Shh)+ progenitor cells and the SHH-responsive capsular Gli1+ cells to the
      regenerating adrenal cortex, we observed a spatially and temporally bimodal
      contribution of both cell types to adrenocortical regeneration following
      cessation of glucocorticoid treatment. First, an early repopulation of the cortex
      is defined by a marked delamination and expansion of capsular Gli1+ cells,
      recapitulating the establishment of the capsular-cortical homeostatic niche
      during embryonic development. This rapid repopulation is promptly cleared from
      the cortical compartment only to be supplanted by repopulating cortical cells
      derived from the resident long-term-retained zona glomerulosa Shh+ progenitors.
      Pharmacologic and genetic dissection of SHH signaling further defines an SHH
      dependent activation of WNT signaling that supports regeneration of the cortex
      following long-term glucocorticoid therapy. We define the signaling and lineage
      relationships that underlie the regeneration process.

PMID- 29211851
TI  - Cohort Profile: The Heinz C. Prechter Longitudinal Study of Bipolar Disorder.

PMID- 29211855
TI  - A rabbit model of progressive chronic right ventricular pressure overload.
AB  - OBJECTIVES: Right ventricular (RV) failure from increased pressure loading is a
      frequent consequence of acquired and congenital heart diseases. However, the
      mechanisms involved in their pathophysiology are still unclear, and few data
      exist on RV pressure-loading models and early versus late effects on RV and left
      ventricular responses. We characterized a rabbit model of chronic RV pressure
      overload and early-late effects on biventricular function. METHODS: Twenty-one
      New Zealand white rabbits were randomized into 3 groups: (i) sham, (ii) pulmonary
      artery (PA) banding (PAB) for 3 weeks (PAB3W) and (iii) PAB for 6 weeks (PAB6W).
      Progressive RV pressure overload was created by serial band inflation using an
      adjustable device. Molecular, echocardiographic and haemodynamic studies were
      performed. RESULTS: RV pressure overload was achieved with clinical
      manifestations of RV failure. Heart and liver weights were significantly higher
      after PAB. PAB-induced echocardiographic ventricular remodelling increased wall
      thickness and stress and ventricular dilation. Cardiac output (ml/min) (sham
      172.4 +/- 42.86 vs PAB3W 103.1 +/- 23.14 vs PAB6W 144 +/- 60.9, P = 0.0027) and
      systolic and diastolic functions decreased; with increased RV end-systolic and
      end-diastolic pressures (mmHg) (sham 1.6 +/- 0.66 vs PAB3W 3.9 +/- 1.8 vs PAB6W
      5.2 +/- 2.2, P = 0.0103), despite increased contractility [end-systolic pressure
      volume relationship (mmHg/ml), sham 3.76 +/- 1.76 vs PAB3W 12.21 +/- 3.44 vs
      PAB6W 19.4 +/- 6.88, P < 0.0001]. Functional parameters further worsened after
      PAB6W versus PAB3W. LV contractility increased in both the PAB groups, despite
      worsening of other invasive measures of systolic and diastolic functions.
      CONCLUSIONS: We describe a novel, unique model of chronic RV pressure overload
      leading to early biventricular dysfunction and fibrosis with further progression
      at 6 weeks. These findings can aid in guiding management.

PMID- 29211852
TI  - Migration-Selection Balance Drives Genetic Differentiation in Genes Associated
      with High-Altitude Function in the Speckled Teal (Anas flavirostris) in the
      Andes.
AB  - Local adaptation frequently occurs across populations as a result of migration
      selection balance between divergent selective pressures and gene flow associated
      with life in heterogeneous landscapes. Studying the effects of selection and gene
      flow on the adaptation process can be achieved in systems that have recently
      colonized extreme environments. This study utilizes an endemic South American
      duck species, the speckled teal (Anas flavirostris), which has both high- and low
      altitude populations. High-altitude speckled teal (A. f. oxyptera) are locally
      adapted to the Andean environment and mostly allopatric from low-altitude birds
      (A. f. flavirostris); however, there is occasional gene flow across altitudinal
      gradients. In this study, we used next-generation sequencing to explore genetic
      patterns associated with high-altitude adaptation in speckled teal populations,
      as well as the extent to which the balance between selection and migration have
      affected genetic architecture. We identified a set of loci with allele
      frequencies strongly correlated with altitude, including those involved in the
      insulin-like signaling pathway, bone morphogenesis, oxidative phosphorylation,
      responders to hypoxia-induced DNA damage, and feedback loops to the hypoxia
      inducible factor pathway. These same outlier loci were found to have depressed
      gene flow estimates, as well as being highly concentrated on the Z-chromosome.
      Our results suggest a multifactorial response to life at high altitudes through
      an array of interconnected pathways that are likely under positive selection and
      whose genetic components seem to be providing an effective genomic barrier to
      interbreeding, potentially functioning as an avenue for population divergence and
      speciation.

PMID- 29211854
TI  - Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment
      elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells.
AB  - Aims: In patients with acute coronary syndrome (ACS), the higher activity of
      effector T-cells suggests that mechanisms involving adaptive immunity
      dysregulation might play a role in coronary instability. The shedding of the
      functional CD31 domain 1-5 leads to uncontrolled lymphocyte activation. In
      experimental models, matrix metalloproteinase-9 (MMP-9) has been implicated in
      endothelial CD31 cleavage. Interestingly, higher serum levels of MMP-9 have been
      observed in ACS. We aim to investigate the mechanisms underlying CD31
      dysregulation in ACS. Methods and results: To assess CD31 cleavage on CD4+ T
      cells, we analysed by flow cytometry CD4+ T-cells of 30 ACS, 25 stable angina
      (SA) patients, and 28 controls (CTRL) using two different CD31 antibodies that
      specifically recognize domain 1-5 or the non-functional membrane-proximal domain
      6. The ratio between the domains was significantly lower in ACS than in SA and
      CTRL (P = 0.002 ACS vs. SA; P = 0.002 ACS vs. CTRL). After stimulation with anti
      CD3/CD28, the 1-5/6 domain ratio was significantly lower in ACS than in SA (P =
      0.005). ELISA of supernatants obtained from T-cell receptor-stimulated CD4+ T
      cells showed higher production of MMP-9 in ACS than in SA (P < 0.001). CD31
      domain 1-5 expression in activated CD4+ T-cells from ACS patients increased after
      treatment with a specific MMP-9 inhibitor (P = 0.042). Conclusion: Our study
      suggest that enhanced MMP-9 release plays a key role in determining the cleavage
      and shedding of the functional CD31 domain 1-5 in CD4+ T-cells of ACS patients.
      This mechanism might represent an important therapeutic target to modulate T-cell
      dysregulation in ACS.

PMID- 29211853
TI  - Nrf2 Deficiency Upregulates Intrarenal Angiotensin-Converting Enzyme-2 and
      Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy
      in Diabetic Mice.
AB  - We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in
      renin-angiotensin system (RAS) gene expression in renal proximal tubule cells
      (RPTCs) and in the development of systemic hypertension and kidney injury in
      diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice
      treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We
      also examined rat immortalized RPTCs (IRPTCs) stably transfected with control
      plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting
      enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1
      7) receptor (MasR) gene promoters. Genetic deletion of Nrf2 or pharmacological
      inhibition of Nrf2 in Akita mice attenuated hypertension, renal injury,
      tubulointerstitial fibrosis, and the urinary albumin/creatinine ratio.
      Furthermore, loss of Nrf2 upregulated RPTC Ace2 and MasR expression, increased
      urinary Ang 1-7 levels, and downregulated expression of Agt, ACE, and profibrotic
      genes in Akita mice. In cultured IRPTCs, Nrf2 small interfering RNA transfection
      or trigonelline treatment prevented high glucose stimulation of Nrf2 nuclear
      translocation, Agt, and ACE transcription with augmentation of Ace2 and MasR
      transcription, which was reversed by oltipraz. These data identify a mechanism,
      Nrf2-mediated stimulation of intrarenal RAS gene expression, by which chronic
      hyperglycemia induces hypertension and renal injury in diabetes.

PMID- 29211856
TI  - Long-term mortality in patients with atrial septal defect: a nationwide cohort
      study.
AB  - Aims: In this nationwide cohort of atrial septal defect (ASD) patients, the
      largest to date, we report the longest follow-up time with and without closure in
      childhood and adulthood compared with a general population cohort. Methods and
      results: Using population-based registries, we included Danish individuals born
      before 1994 who received an ASD diagnosis between 1959 and 2013. All diagnoses
      were subsequently validated (n = 2277). Using the Kaplan-Meier estimates and Cox
      proportional hazards regression adjusted for sex, birth year, and a modified
      Charlson Comorbidity Index, we compared the mortality of ASD patients with that
      of a birth year and sex matched general population cohort. The median follow-up
      from ASD diagnosis was 18.1 years (range 1-53 years). Patients with ASD had a
      higher mortality [adjusted hazard ratio (HR): 1.7; 95% confidence interval (CI):
      1.5-1.9] compared with the general population cohort. The adjusted HR 30 days
      after closure was 1.4 (95% CI: 1.2-1.7), and it was 2.4 (95% CI: 2.0-2.9) for
      patients without closure. Conclusion: Overall, ASD patients had a higher long
      term mortality than a general population cohort matched on birth year and gender.
      Our data indicate a lower relative mortality of those ASD patients undergoing
      closure than the ASD patients not undergoing closure.

PMID- 29211857
TI  - PulmOnary vein isolation With vs. without continued antiarrhythmic Drug trEatment
      in subjects with Recurrent Atrial Fibrillation (POWDER AF): results from a
      multicentre randomized trial.
AB  - Aims: Catheter ablation is indicated in patients with symptomatic paroxysmal
      atrial fibrillation (AF) resistant to antiarrhythmic drug therapy (ADT). We
      investigated whether continued use of previously ineffective ADT beyond the post
      ablation blanking period reduces recurrence of atrial tachyarrhythmia within the
      1st year after ablation. Methods and results: This was a multicentre, randomized
      controlled study in patients undergoing contact force-guided pulmonary vein
      isolation (PVI) for paroxysmal AF in whom previously ineffective ADT was
      continued during a blanking period of 3 months. If free of AF at the end of the
      blanking period, patients were randomly assigned in the ratio of 1:1 to continue
      ADT (ADT ON group, n = 77) or discontinue ADT (ADT OFF group, n = 76). Patients
      were followed up until 1 year after PVI, with clinical visits, Holter monitoring,
      and quality-of-life (QOL) questionnaires at 6 and 12 months post-procedure.
      Analysis of the primary endpoint (any documented atrial tachyarrhythmia lasting
      >30 s) was performed according to the modified intention-to-treat principle.
      Secondary endpoints included repeat ablation, unscheduled visits, and QOL score.
      Baseline clinical characteristics and initial ablation procedure characteristics
      were comparable between both groups. Three patients were lost to follow-up in
      each arm. The primary endpoint was observed in 2 of 74 (2.7%) patients in the ADT
      ON group vs. 16 of 73 (21.9%) patients in the ADT OFF group (P < 0.001). The ADT
      ON group had a lower rate of repeat ablation [1.4% vs. 19.2%, hazard ratio (HR) =
      0.053; 95% confidence interval (CI) 0.007-0.399; P < 0.01) and less unscheduled
      arrhythmia-related health care visits (2.7% vs. 20.5%, HR = 0.055, 95% CI 0.007
      0.410; P < 0.01). Quality-of-life scores were similar in both groups. Conclusion:
      In patients free of AF at the end of 3 months of post-ablation blanking period,
      continued use of previously ineffective ADT significantly reduces the recurrence
      of atrial tachyarrhythmia in the 1st year after PVI.

PMID- 29211858
TI  - Iohexol plasma clearance simplified by dried blood spot testing.
AB  - Background: Renal function can be estimated with formulas, which are inaccurate,
      or measured with gold standard methods, which are reliable but unpractical. We
      propose to simplify the plasma clearance of iohexol, a gold standard method to
      measure renal function, by dried blood spot (DBS) testing. Methods: We compared
      glomerular filtration rate (GFR) values assessed by DBS and the reference plasma
      analysis technique. We tested in vitro the agreement between non-volumetric and
      volumetric DBS with the reference technique. Then, we performed a clinical
      validation in vivo between volumetric DBS and plasma analysis in 203 patients.
      The agreement was evaluated with the concordance correlation coefficient (CCC),
      the total deviation index (TDI) and the coverage probability. We defined
      acceptable agreement as a TDI <10%. Results: In the in vitro studies, the non
      volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric
      method showed better but insufficient agreement, TDI = 13.0%, with the reference
      method in plasma. The non-volumetric DBS was rejected. To improve the agreement
      of the volumetric DBS, iopamidol was used as an internal standard. This method
      showed acceptable agreement, TDI = 9.0% with the analysis in plasma, and was
      selected as the definitive DBS method. In the in vivo studies, the agreement
      between the final DBS method and the reference technique was acceptable: TDI =
      9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5%
      compared with the reference method. Conclusions: We simplified the plasma
      clearance of iohexol using DBS without losing accuracy and precision with respect
      to the reference technique. This may facilitate the use of a reliable
      determination of renal function to the medical community.

PMID- 29211859
TI  - Transformation asymmetry and the evolution of the bacterial accessory genome.
AB  - Bacterial transformation can insert or delete genomic islands (GIs), depending on
      the donor and recipient genotypes, if an homologous recombination spans the GI's
      integration site and includes sufficiently long flanking homologous arms.
      Combining mathematical models of recombination with experiments using pneumococci
      found GI insertion rates declined geometrically with the GI's size. The decrease
      in acquisition frequency with length (1.08x10-3 bp-1) was higher than a previous
      estimate of the analogous rate at which core genome recombinations terminated.
      Although most efficient for shorter GIs, transformation-mediated deletion
      frequencies did not vary consistently with GI length, with removal of 10 kb GIs
      approximately 50% as efficient as acquisition of base substitutions. Fragments of
      two kilobases, typical of transformation event sizes, could drive all these
      deletions independent of island length. The strong asymmetry of transformation,
      and its capacity to efficiently remove GIs, suggests non-mobile accessory loci
      will decline in frequency without preservation by selection.

PMID- 29211860
TI  - Changes in the epigenome and transcriptome of the poplar shoot apical meristem in
      response to water availability affect preferentially hormone pathways.
AB  - The adaptive capacity of long-lived organisms such as trees to the predicted
      climate changes, including severe and successive drought episodes, will depend on
      the presence of genetic diversity and phenotypic plasticity. Here, the
      involvement of epigenetic mechanisms in phenotypic plasticity toward soil water
      availability was examined in Populus*euramericana. This work aimed at
      characterizing (i) the transcriptome plasticity, (ii) the genome-wide plasticity
      of DNA methylation, and (iii) the function of genes affected by a drought
      rewatering cycle in the shoot apical meristem. Using microarray chips,
      differentially expressed genes (DEGs) and differentially methylated regions
      (DMRs) were identified for each water regime. The rewatering condition was
      associated with the highest variations of both gene expression and DNA
      methylation. Changes in methylation were observed particularly in the body of
      expressed genes and to a lesser extent in transposable elements. Together, DEGs
      and DMRs were significantly enriched in genes related to phytohormone metabolism
      or signaling pathways. Altogether, shoot apical meristem responses to changes in
      water availability involved coordinated variations in DNA methylation, as well as
      in gene expression, with a specific targeting of genes involved in hormone
      pathways, a factor that may enable phenotypic plasticity.

PMID- 29211862
TI  - Reply to Magreault et al.

PMID- 29211861
TI  - Spontaneous Microguidewire Extrusion From the Foot Following Cerebral Aneurysm
      Treatment: First Case Report.
AB  - BACKGROUND AND IMPORTANCE: Microguidewire entrapment and failure related to
      endovascular therapy is a rare complication with limited case reports available,
      most of which are from cardiac endovascular intervention. Migration of the
      microguidewire has been reported in coronary intervention with some resulting in
      severe complications, but there are no reported cases of spontaneous extrusion of
      wire fragment following a neurointerventional procedure. We report the first case
      of a microguidewire entrapment with subsequent fracture, followed by spontaneous
      extrusion of the wire fragment. CLINICAL PRESENTATION: A 40-yr-old woman was
      admitted for an elective flow-diversion stent treatment of an unruptured
      paraophthalamic aneurysm. Microguidewire entrapment occurred during an attempted
      balloon-aided dilatation of the partially opened stent. Careful attempts failed
      to retrieve the wire; hence, the decision was made to leave it behind. She
      presented to her family doctor 6 mo later with spontaneous extrusion of a 60-cm
      fragment of the retained wire, from her heel ipsilateral to the femoral puncture
      site. This had not resulted in any further vascular or non-vascular
      complications. CONCLUSION: Fracture with extrusion is a potential consequence of
      a retained microguidewires. While this is an extremely rare complication, it is
      important to alert clinicians and patient about the possibility of wire migration
      and extrusion. Early follow-up with clinical assessment, and targeted imaging
      should lead to identification of this occurrence.

PMID- 29211864
TI  - Right Retrosigmoid Presigmoid Transpetrosal Approach for Resection of Pontine
      Cavernoma: 2-Dimensional Operative Video.

PMID- 29211863
TI  - High Serum TSH Level Is Associated With Progression of Papillary Thyroid
      Microcarcinoma During Active Surveillance.
AB  - Objective: Thyroid-stimulating hormone (TSH) is a growth factor affecting
      initiation or progression of papillary thyroid cancer (PTC), which supports TSH
      suppressive therapy in patients with PTC. In patients with papillary thyroid
      microcarcinoma (PTMC) during active surveillance, however, the association
      between serum TSH level and growth of PTMC has not been demonstrated. Patients:
      We analyzed 127 PTMCs in 126 patients under active surveillance with serial serum
      TSH measurement and ultrasonography. Design: The patients were categorized into
      groups with the highest, middle, and lowest time-weighted average of TSH (TW
      TSH). PTMC progression was defined as a volume increase of >=50% compared with
      baseline. Kaplan-Meier survival analysis according to TW-TSH groups and Cox
      proportional hazard modeling was performed. We identified the cutoff point for
      TSH level by using maximally selected log-rank statistics. Results: During a
      median follow-up of 26 months, PTMC progression was detected in 28 (19.8%)
      patients. Compared with the lowest TW-TSH group, the adjusted hazard ratio (HR)
      for PTMC progression in the highest TW-TSH group was significantly higher [HR
      3.55; 95% confidence interval (CI), 1.22 to 10.28; P = 0.020], but that in the
      middle TW-TSH group was not (HR 1.52; 95% CI, 0.46 to 5.08; P = 0.489). The
      cutoff point for the serum TSH level for PTMC progression was 2.50 mU/L.
      Conclusions: Sustained elevation of serum TSH levels during active surveillance
      is associated with PTMC progression. Maintaining a low-normal TSH range with
      levothyroxine treatment during active surveillance of PTMC might be considered in
      future studies.

PMID- 29211865
TI  - The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract
      Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent
      Brain Lesions.
AB  - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) enables
      preoperative mapping of the motor cortex (M1). The combination of nTMS with
      diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST)
      has been described; however, its impact on surgery of motor-eloquent lesions has
      not been addressed. OBJECTIVE: To analyze the impact of nTMS-based mapping on
      surgery of motor-eloquent lesions. METHODS: In this retrospective case-control
      study, we reviewed the data of patients operated for suspected motor-eloquent
      lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and,
      from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative
      risk/benefit analysis, surgical strategy, craniotomy size, extent of resection
      (EOR), and outcome were compared with a control group. RESULTS: We included 35
      patients who underwent nTMS mapping of M1 (group A), 35 patients who also
      underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of
      35 patients treated without nTMS (group C). The patients in groups A and B
      received smaller craniotomies (P = .01; P = .001), had less postoperative
      seizures (P = .02), and a better postoperative motor performance (P = .04) and
      Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an
      improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative
      lesions in absence of preoperative motor deficits (P = .01), and less motor and
      Karnofsky Performance Status worsening in case of preoperative motor deficits (P
      = .02, P = .03) than group A. CONCLUSION: nTMS-based mapping enables a tailored
      surgical approach for motor-eloquent lesions. It may improve the risk/benefit
      analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed.

PMID- 29211866
TI  - Association of Urinary Citrate With Acid-Base Status, Bone Resorption, and
      Calcium Excretion in Older Men and Women.
AB  - Context: Elevated urine net acid excretion (NAE), indicative of subclinical
      metabolic acidosis, has been associated with higher bone turnover. Urine citrate,
      which is a common clinical measure, changes in response to acid-base status but
      its association with bone turnover is uncertain. Objective: We evaluated the
      association between change in urine citrate and change in bone turnover and
      calcium excretion. Design, Intervention, and Participants: A total of 233 healthy
      men and women >=60 years old were randomly assigned to 1.0 mmol/kg/d potassium
      bicarbonate (KHCO3), 1.5 mmol/kg/d KHCO3, or placebo for 84 days. Outcome
      Measures: Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium
      excretion, and serum amino-terminal propeptide of type 1 procollagen (P1NP) were
      measured before and after intervention. Results: Urine citrate increased dose
      dependently after KHCO3 supplementation (P trend < 0.001). The urine citrate
      change was significantly inversely associated with P1NP change (P = 0.021) but
      not with change in NTX (P = 0.051) or calcium excretion (P = 0.652). The NAE
      change was positively associated with change in NTX and calcium excretion (P <=
      0.003) but not with change in P1NP (P = 0.051). When the urine citrate change and
      NAE change were included in the same model, the urine citrate change was not
      associated with change in NTX, calcium excretion, or serum P1NP (P >= 0.086),
      whereas change in NAE remained associated with change in NTX and calcium
      excretion (P <= 0.003). Conclusion: Urine citrate may not be a suitable
      alternative to NAE when assessing acid-base status in relation to bone turnover
      in older adults.

PMID- 29211868
TI  - In Reply: Contralateral Anterior Interhemispheric Approach to Medial Frontal
      Arteriovenous Malformations: Surgical Technique and Results.

PMID- 29211867
TI  - Effects of corn dried distillers' grains with solubles on performance, egg
      quality, yolk fatty acid composition and oxidative status in laying ducks.
AB  - The study investigated the effects of increasing content of corn distillers'
      dried grains with solubles (DDGS) in the diets of laying ducks on oxidative
      status, laying performance, egg quality, and egg yolk fatty acid composition.
      Longyan females (1080) with similar BW at 17 wk of age were randomly assigned to
      6 treatment groups, each consisting of 6 replicates of 30 birds. The basal diet
      (I) was a typical corn-soybean ration while the experimental diets (II to VI)
      substituted corn DDGS for soybean meal and wheat bran and a small reduction of
      corn. The level of substitution in diets (II to VI) was 6%, 12%, 18%, 24% and
      30%. The experiment lasted for 18 wk. Average egg weight decreased linearly as
      the level of corn DDGS inclusion increased (P < 0.001). Haugh unit, albumen
      weight, and proportion declined as linear responses to corn DDGS substitution (P
      < 0.05), but yolk color linearly increased (P < 0.001); the proportions of oleic
      (C18:1) and total monounsaturated fatty acids in egg yolk linearly decreased with
      increasing corn DDGS and many of the key polyunsaturated fatty acids (PUFAs) like
      linoleic (C18:2n-6), arachidonic (C20:4n-6) and alpha-linolenic (C18:3n-3) acids
      linearly increased (P < 0.001), but not those of eicosapentaenoic (C20:5n-3) and
      docoshexaenoic (C22:6n-3) acids. The PUFAs n-6/n-3 ratio linearly increased with
      increasing corn DDGS level (P < 0.001). Increasing corn DDGS linearly increased
      hepatic expression of GPX1, HO-1, and Nrf2 and hepatic activity of GSH-Px and the
      liver content of MDA (P < 0.001). There were no treatment effects on egg
      production, egg mass, feed conversion ratio, eggshell thickness, strength, and
      yolk cholesterol content (P > 0.05). In conclusion, the current study indicates
      that the use of corn DDGS is possible as a replacement, primarily for soybean
      meal at levels up to 18% in the diets of laying ducks without affecting laying
      performance, egg quality, and antioxidant status. Increasing amounts of corn DDGS
      linearly increased egg yolk concentrations of key fatty acids like like C18:2n-6
      and C18:3n-3 and the antioxidant enzyme activity of GSH-Px through the Nrf2
      pathway to avoid oxidative stress.

PMID- 29211869
TI  - The Dark Side of Light Traps.
AB  - Light-baited suction traps are one of the most widely used tools for vector
      surveillance. Their popularity stems from ease of use even in remote locations,
      range and abundance of species caught, and low cost. The availability of smaller,
      portable models, like the CDC miniature light trap, have further increased their
      ubiquity in entomological field studies. However, when researchers have looked,
      light trap collections are usually biased in ways that may affect data
      interpretation for epidemiological studies. If used alone, light traps may fail
      to collect important or infected vectors, and light traps are inefficient or
      ineffective when competing ambient light is present. In this article, we discuss
      these biases and limitations in terms of their effect on collection efficiency,
      population data, and pathogen detection. While light trap data certainly have a
      purpose, an over-reliance on light trapping risks drawing false conclusions about
      vector populations and vector-borne disease epidemiology. These concerns are
      especially troubling when light trap data are used to inform policy decisions
      meant to protect human and animal health. Particularly when a species' response
      to light is unknown or poorly characterized, light traps should be used in
      conjunction with supplemental sampling methods. Researchers conducting vector
      surveillance field studies should carefully consider their study design and
      objectives when deciding on a trapping method or methods, and specifically
      endeavor to understand the limitations of their data. Only then can researchers
      take advantage of the best attributes of light traps while avoiding their dark
      side.

PMID- 29211870
TI  - Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With
      Denosumab for Giant Cell Tumor of Bone.
AB  - Context: Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B
      ligand, is an approved treatment of giant cell tumor of bone (GCTB) in adults and
      "skeletally mature" adolescents. Safety concerns include oversuppression of bone
      remodelling, with risk of osteonecrosis of the jaw (ONJ) and atypical femur
      fractures during treatment in adults and rebound hypercalcemia after treatment
      cessation in children. To date, ONJ has never been reported in children or
      adolescents. Objectives: To describe serious adverse effects during and following
      high-dose denosumab therapy in GCTB patients. Patients: Two adolescents (14 and
      15 years) and a young adult (40 years) received fixed-dose denosumab for GCTB for
      1.3 to 4 years (cumulative dose, 47 to 98 mg/kg), which was stopped because of
      development of ONJ in one adolescent and bilateral femoral cortical stress
      reactions in the young adult. All three patients developed rebound hypercalcemia
      with acute kidney injury 5.5 to 7 months after denosumab cessation. Results: The
      ONJ necessitated surgical debridement. Rebound hypercalcemia (serum calcium, 3.1
      to 4.3 mmol/L) was unresponsive to hyperhydration alone, requiring repeated doses
      of calcitonin or intravenous bisphosphonate treatment. Hypercalcemia recurred in
      two patients within 4 weeks, with normal serum calcium profiles thereafter. All
      patients were naive to chemotherapy, radiotherapy, bisphosphonates, and
      corticosteroids and were metastases free, confirming the causative role of
      denosumab in these complications. Conclusion: These suppression-release effects
      of high-dose denosumab on bone remodeling raise questions about safety of fixed
      dosing and treatment duration. In young people, weight-adjusted dosing and safety
      monitoring during and after antiresorptive therapy is required.

PMID- 29211872
TI  - Misplacement of Stent Into Epidural Venous Plexus With Resultant Cauda Equina
      Syndrome and Open Surgical Treatment: A Case Report.
AB  - BACKGROUND AND IMPORTANCE: Endovascular therapy has proven to be a safe,
      minimally invasive treatment for multiple etiologies, but proper precautions must
      be taken to avoid complications. When complications occur, they should be
      promptly identified and corrected when possible. This case report describes
      endovascular stents misplaced into the epidural spinous venous plexus rather than
      the iliofemoral arteries, causing cauda equina syndrome, as well as the spinal
      procedure performed to treat the resulting spinal canal compression. CLINICAL
      PRESENTATION: A 67-yr-old man had undergone what he thought was iliofemoral
      arterial stenting at an outside hospital for peripheral vascular disease. He
      presented 8 d later to our hospital with cauda equina syndrome comprising back
      pain, right L5 radiculopathy, perianal numbness, urinary retention, and
      constipation. Scans demonstrated stents deployed into the venous system,
      traversing the spinal canal and the right L5-S1 neural foramen, resulting in
      severe spinal canal stenosis, right L5-S1 foraminal stenosis, and moderate left
      S1-S2 foraminal stenosis. The patient underwent an L5-S1 laminectomy with full
      right L5-S1 facetectomy and left S1-S2 medial facetectomy, with associated L5-S1
      posterolateral fusion with fixation to remove the stent and decompress the neural
      elements. CONCLUSION: Although stent misplacement is an uncommon complication of
      endovascular therapy, this case demonstrates the importance of ensuring access to
      the proper vessel before stent placement. Once this complication was recognized,
      safe removal of the stents was possible and the patient demonstrated meaningful
      postoperative improvement in symptoms and strength.

PMID- 29211871
TI  - Pramlintide but Not Liraglutide Suppresses Meal-Stimulated Glucagon Responses in
      Type 1 Diabetes.
AB  - Context: Postprandial hyperglycemia remains a challenge in type 1 diabetes (T1D)
      due, in part, to dysregulated increases in plasma glucagon levels after meals.
      Objective: This study was undertaken to examine whether 3 to 4 weeks of therapy
      with pramlintide or liraglutide might help to blunt postprandial hyperglycemia in
      T1D by suppressing plasma glucagon responses to mixed-meal feedings. Design: Two
      parallel studies were conducted in which participants underwent mixed-meal
      tolerance tests (MMTTs) without premeal bolus insulin administration before and
      after 3 to 4 weeks of treatment with either pramlintide (8 participants aged 20
      +/- 3 years, hemoglobin A1c 6.9 +/- 0.5%) or liraglutide (10 participants aged 22
      +/- 3 years, hemoglobin A1c 7.6 +/- 0.9%). Results: Compared with pretreatment
      responses to the MMTT, treatment with pramlintide reduced the peak increment in
      glucagon from 32 +/- 16 to 23 +/- 12 pg/mL (P < 0.02). In addition, the
      incremental area under the plasma glucagon curve from 0 to 120 minutes dropped
      from 1988 +/- 590 to 737 +/- 577 pg/mL/min (P < 0.001), which was accompanied by
      a similar reduction in the meal-stimulated increase in the plasma glucose curve
      from 11,963 +/- 1424 mg/dL/min pretreatment vs 2493 +/- 1854 mg/dL/min after
      treatment (P < 0.01). In contrast, treatment with liraglutide had no effect on
      plasma glucagon and glucose responses during the MMTT. Conclusions: Adjunctive
      treatment with pramlintide may provide an effective means to blunt postmeal
      hyperglycemia in T1D by suppressing dysregulated plasma glucagon responses. In
      contrast, plasma glucose and glucagon responses were unchanged after 3 to 4 weeks
      of treatment with liraglutide.

PMID- 29211873
TI  - Association Between Sporadic Legionellosis and River Systems in Connecticut.
AB  - Background: There has been a dramatic increase in the incidence of sporadic
      legionnaires' disease in Connecticut since 1999, but the exact reasons for this
      are unknown. Therefore, there is a growing need to understand the drivers of
      legionnaires' disease in the community. In this study, we explored the
      relationship between the natural environment and the spatial and temporal
      distribution of legionellosis cases in Connecticut. Methods: We used spatial
      models and time series methods to evaluate factors associated with the increase
      and clustering of legionellosis in Connecticut. Stream flow, proximity to rivers,
      and residence in regional watersheds were explored as novel predictors of
      disease, while controlling for testing intensity and correlates of urbanization.
      Results: In Connecticut, legionellosis incidence exhibited a strong pattern of
      spatial clustering. Proximity to several rivers and residence in the
      corresponding watersheds were associated with increased incidence of the disease.
      Elevated rainfall and stream flow rate were associated with increases in
      incidence 2 weeks later. Conclusions: We identified a novel relationship between
      the natural aquatic environment and the spatial distribution of sporadic cases of
      legionellosis. These results suggest that natural environmental reservoirs may
      have a greater influence on the spatial distribution of sporadic legionellosis
      cases than previously thought.

PMID- 29211874
TI  - Prevalence, Incidence, and Clearance of Anal High-Risk Human Papillomavirus
      Infection Among HIV-Infected Men in the SUN Study.
AB  - Background: The natural history of anal human papilloma virus (HPV) infection
      among human immunodeficiency virus (HIV)-infected men is unknown. Methods:
      Annually, from 2004 to 2012, we examined baseline prevalence, incidence, and
      clearance of anal HPV infection at 48 months, and associated factors among HIV
      infected men. Results: We examined 403 men who have sex with men (MSM) and 96 men
      who have sex with women (MSW) (median age 42 years for both, 78% versus 81%
      prescribed cART, median CD4+ T-lymphocyte cell count 454 versus 379 cells/mm3,
      and 74% versus 75% had undetectable viral load, respectively). Type 16 prevalence
      among MSM and MSW was 38% versus 14% (P < .001), and incidence 24% versus 7% (P =
      .001). Type 18 prevalence was 24% versus 8% (P < .001), and incidence 13% versus
      4% (P = .027). Among MSM and MSW, clearance of prevalent HPV 16 and HPV 18 was
      31% and 60% (P = .392), and 47% and 25% (P = .297), respectively. Among MSM,
      receptive anal sex (with or without a condom) was associated with persistent HPV
      16 (OR 2.24, P < .001). Conclusions: MSM had higher prevalence and incidence of
      HPV than MSW, but similar clearance. Receptive anal sex may predict cancer risk
      among HIV-infected MSM.

PMID- 29211875
TI  - The safety and efficacy of radiofrequency ablation following endoscopic
      submucosal dissection for Barrett's neoplasia.
AB  - The current standard of treating early Barrett's neoplasia is resection of
      visible lesions using endoscopic mucosal resection (EMR) followed by ablative
      therapy to the Barrett's segment. There is increasing evidence to support the use
      of endoscopic submucosal dissection (ESD) where en-bloc resection and lower
      recurrence rates may be achieved. However, ESD is associated with deep submucosal
      dissection when compared to EMR. This may increase the risk of complications
      including stricture formation with subsequent radiofrequency ablation (RFA)
      therapy. The aim of this study is to compare the safety and efficacy of RFA
      following EMR and ESD as well as when RFA was used without prior endoscopic
      resection. The primary outcome measure was complication rates. Clearance of
      dysplasia (CRD) and clearance of intestinal metaplasia (CRIM) were secondary
      outcomes. A retrospective analysis of a cohort of 91 patients referred for RFA
      from a single academic tertiary center was performed. The choice of endoscopic
      resection method was tailored according to the lesion type and morphology. Focal
      and circumferential ablation was performed after initial follow up endoscopy
      postresection. Patients proceeded straight to RFA in the absence of any visible
      lesions. In this study, the ESD group had a higher proportion of cancers compared
      to the EMR cohort (74.1% vs. 30.2%, P < 0.01) prior to RFA. All complications
      post RFA occurred in the groups with previous endoscopic resection. There was no
      significant difference in the total complication rate (7.4% vs. 9.3%, P = 0.78)
      and stricture formation rate (3.7% vs. 9.3%, P = 0.38) between the ESD and EMR
      groups. CRD was achieved in 96.3% in the ESD group, 88.4% in the EMR group, and
      all patients in the RFA alone group. CRIM rates were similar in the EMR and ESD
      groups (81.4% vs. 85.2%) but higher in the RFA alone group (90.5%). In
      conclusion, RFA following ESD is very effective and not associated with an
      increased risk of complications compared to EMR. This supports the application of
      RFA in the treatment algorithm of patients undergoing ESD for Barrett's
      neoplasia.

PMID- 29211876
TI  - Interplay between FMRP and lncRNA TUG1 regulates axonal development through
      mediating SnoN-Ccd1 pathway.
AB  - LncRNAs have recently emerged to influence the pathogenesis of fragile X syndrome
      (FXS), which is caused by the functional loss of fragile X mental retardation
      protein (FMRP). However, the interaction between FMRP and lncRNAs on regulating
      neuronal development remains elusive. Here, we reported that FMRP directly
      interacted with lncRNA TUG1, and decreased its stability. Furthermore, TUG1 bond
      to transcriptional regulator, SnoN, and negatively modulated SnoN-Ccd1 pathway to
      specifically control axonal development. These observations suggested interplay
      between FMRP and lncRNAs might contribute to the pathogenesis of FXS.

PMID- 29211878
TI  - Normal reference values of multilayer longitudinal strain according to age
      decades in a healthy population: A single-centre experience.
AB  - Aims: Recent advancements in echocardiographic technology allow to analyse
      myocardial strain in multiple layers. Little is known about the impact of age on
      layer-specific longitudinal strain in healthy subjects. The aim of this study was
      to analyse the influence of age on multilayer longitudinal strain and establish
      normal reference values of layer-specific strain according to age decades in a
      healthy population referring to our echo laboratory using 2D speckle-tracking
      echocardiography with layer-specific software. Methods and results: Two-hundred
      sixty-six healthy, consecutive subjects (mean age = 39.2 +/- 17.5 years,
      women/men = 137/129), free of cardiovascular risk factors, were enrolled.
      Subjects were divided according to six age decades: 10-19, 20-29, 30-39, 40-49,
      50-59, >60 years. All subjects underwent a complete echo Doppler examination
      including quantitation of 2D global longitudinal strain (GLS). Subendocardial
      longitudinal strain (LSsubendo), subepicardial longitudinal strain (LSsubepi),
      and strain gradient (LSsubendo - LSsubepi) were also determined. GLS (P < 0.001),
      LSsubendo, and LSsubepi (both P < 0.0001) were all progressively reduced with
      increasing age decades, but post hoc intra-group analyses demonstrated that the
      decline of GLS, LSsubendo, and LSsubepi was significant in the decades 50-60 and
      >=60 years. In separate multiple linear regression analyses, the effect of age on
      GLS, LSsubendo, and LSsubepi remained significant even after adjusting for
      clinical and echocardiographic confounders. Strain gradient remained unchanged in
      age decades. Conclusion: Ageing shows an independent effect on GLS, LSsubendo,
      and, particularly on, LSsubepi. Our data also provide normal reference values of
      layer-specific longitudinal strain for age decades.

PMID- 29211877
TI  - Delivering precision antimicrobial therapy through closed-loop control systems.
AB  - Sub-optimal exposure to antimicrobial therapy is associated with poor patient
      outcomes and the development of antimicrobial resistance. Mechanisms for
      optimizing the concentration of a drug within the individual patient are under
      development. However, several barriers remain in realizing true individualization
      of therapy. These include problems with plasma drug sampling, availability of
      appropriate assays, and current mechanisms for dose adjustment. Biosensor
      technology offers a means of providing real-time monitoring of antimicrobials in
      a minimally invasive fashion. We report the potential for using microneedle
      biosensor technology as part of closed-loop control systems for the optimization
      of antimicrobial therapy in individual patients.

PMID- 29211879
TI  - Cross-Country Comparisons of Disability and Morbidity: Evidence from the Gateway
      to Global Aging Data.
AB  - Background: International comparisons of disease prevalence have been useful in
      understanding what proportion of disease might be preventable and in informing
      potential policy interventions in different cultural and economic contexts. Using
      newly available, harmonized data from 20 countries, we compare disability and
      morbidity of older adults between the ages of 55 and 74. Methods: The Gateway to
      Global Aging Data, a data and information portal, provides access to easy-to-use
      individual-level longitudinal data from 10 surveys covering over 30 countries.
      Exploiting harmonized measures available from the Gateway, we descriptively
      examine how disability and morbidity differ across countries. Results:
      Significant cross-country differences are observed for several health indicators.
      Comparing countries with the highest and lowest prevalence rates, we observe that
      hypertension rates vary twofold and stroke rates vary threefold, while disability
      and arthritis rates vary more than fivefold. Among women, higher gross domestic
      product and life expectancy are related to lower diabetes, heart disease, and
      better functioning. Among men, national indicators of economic conditions are not
      significantly associated with reported disease prevalence. Conclusions: We
      document substantial heterogeneity in disability and morbidity across countries,
      separately for men and women and after controlling for population age composition
      and education. Rich data from various surveys across the world offers remarkable
      opportunities for cross-country analyses, calling for further investigation of
      what drives observed differences. The Gateway to Global Aging Data provides easy
      to-use harmonized data files and tools to facilitate this type of research.

PMID- 29211880
TI  - Corrigendum to: 'Clinical long-term outcome of septal myectomy for obstructive
      hypertrophic cardiomyopathy in infants' [Eur J Cardiothorac Surg 2018;53:538-
      44].

PMID- 29211881
TI  - Food and Feed Safety of Genetically Engineered Food Crops.
AB  - The first genetically engineered (GE) food crop (tomato) was introduced in 1995,
      followed by the successful development and commercial release of maize, soybeans,
      cotton, canola, potatoes, papaya, alfalfa, squash, and sugar beets with specific
      new genetic traits. Even though the safety of every new GE crop has been
      evaluated by various regulatory authorities throughout the world prior to its
      commercial release, the ongoing public debate about the safety of food and feed
      derived from GE plants has not abated. Such debates often overshadow an important
      fact that all crops used as human food or animal feed include varieties that have
      been developed through conventional breeding and selection over hundreds or
      thousands of years, or through intentional but random mutagenesis. Developing
      food crops through such breeding practices result in large-scale genomic changes
      in the resulting crops, and these genomic changes do not undergo molecular
      characterization. In contrast, new GE crops are developed using well
      characterized DNA fragments and the resulting crops are tested and evaluated with
      much greater scrutiny. This document reviews the safety data and information of
      GE crops and foods obtained from them.

PMID- 29211882
TI  - Making epidemiology matter even more!

PMID- 29211883
TI  - Carcass characteristics, meat quality, and fatty acid composition of wild-living
      mallards (Anas platyrhynchos L.).
AB  - The aim of this study was to determine the carcass characteristics, meat quality,
      and fatty acid composition of wild-living mallards. The experimental materials
      comprised 30 mallards (1:1 sex ratio) harvested during the hunting season in
      northeastern Poland. The carcasses were transported to the laboratory where they
      were weighed individually, plucked, dressed, and dissected. The proximate
      chemical composition and physicochemical properties of meat and the fatty acid
      profile of breast muscle lipids were determined, and a histological analysis was
      performed. Body weight (BW) and carcass weight were higher in males than in
      females (P <= 0.05), whereas the percentage share of carcass tissue components
      was similar in both sexes. Edible components accounted for approximately 60% (?)
      to 60.7% (?) of the total BW of mallards, including lean meat; 40.9% (?) to 41.5%
      (?), skin with subcutaneous fat; 10.7% (?) to 10.8% (?), and giblets; 8.3% (?) to
      8.4% (?). Breast muscles had high protein content (23.51%? to 23.6% ?) and low
      fat content (0.82% ? to 0.84% ?). In the fatty acid profile of breast muscle
      lipids, saturated fatty acids (SFA) accounted for 39.1% (?) to 39.04% (?),
      monounsaturated fatty acids (MUFA)-for 17.31% (?) to 17.33% (?) and
      polyunsaturated fatty acids (PUFA)-for 43.61% (?) to 43.64% (?). The diameters of
      type IIA and type IIB muscle fibers were lower in males than in females (P <=
      0.05), whereas lipid storage sites in muscles were similar in both sexes. The
      values of cooking loss (CL), water-holding capacity (WHC), pH24, and color
      parameters of breast meat were comparable in males and females. The results of
      this study indicate that wild-living mallards, both males and females, are
      characterized by high meat quality, and that seasonal mallard harvests can
      provide meat with desirable eating attributes, attractive to consumers.

PMID- 29211885
TI  - Outcome of surgical intervention for aortic root abscess: a meta-analysis.
AB  - OBJECTIVES: Aortic root abscess (ARA) is a catastrophic complication of aortic
      root endocarditis, involving both native and prosthetic valves, which often
      warrants surgical intervention. Currently, aortic valve replacement (AVR) and
      aortic root replacement (ARR) are the most widely employed techniques. However,
      evidence that directly compares these methods is scarce. In this meta-analysis,
      we aimed to describe the surgical outcome of ARA when using different surgical
      methods. METHODS: In this meta-analysis, we performed literature searches in the
      EMBASE and PubMed databases and reviewed articles describing postoperative
      results of ARA that were published before 30 June 2016. After extracting the
      published data, we used a random-effects model to perform meta-analysis and
      compare the postoperative outcomes of ARA after management with AVR or ARR.
      RESULTS: Seven published studies were included in this meta-analysis, which
      includes 781 episodes of infective endocarditis complicated with ARA. There was
      no significant difference in the 30-day postoperative mortality rate among
      patients receiving ARR [23.8%, 95% confidence interval (CI) 17.8-30.6] compared
      with AVR (19.1%, 95% CI 13.3-26.1%), with a relative risk ratio of 1.30 (95% CI
      0.84-2.00). However, patients receiving ARR were associated with statistically
      significant lower rates of reoperation within 1 year (relative risk 0.50, 95% CI
      0.26-0.94). CONCLUSIONS: In our meta-analysis, ARR was associated with a 50% risk
      reduction of reoperation within 1 year among patients with ARA. There was no
      significant difference in the 30-day postoperative mortality rate between
      patients receiving ARR and patients receiving AVR; comparison of the long-term
      outcomes after these 2 procedures warrants further investigation.

PMID- 29211884
TI  - Outcome of current and history of cancer on the risk of cardiovascular events
      following percutaneous coronary intervention: a Kumamoto University Malignancy
      and Atherosclerosis (KUMA) study.
AB  - Aims: With the advancement in successfully treating different types of cancers,
      there is an immediate and increased need to focus on the risk and complexity of
      treating cardiovascular events in cancer survivors. This has led to the emergence
      of onco-cardiology/cardio-oncology field. We examined the varying incidence of
      cardiovascular events after percutaneous coronary intervention (PCI) in patients
      with or without cancer. Methods and results: Participants were divided into a non
      malignant group and a malignant group, consisting of patients who were receiving
      or had ever received cancer treatment. The primary endpoint was target lesion
      revascularization (TLR) within 1 year of PCI. In the patient groups studied, we
      showed that the malignant group had a significantly higher probability of TLR
      than the non-malignant group (P = 0.002). Moreover, proportional hazards analyses
      identified malignancy as an independent predictor of TLR [hazard ratio (HR) 2.28,
      95% confidential interval (CI) 1.3-4.0; P = 0.004]. Combining malignancy status
      with high-sensitivity C-reactive protein levels further increased the HR for TLR
      (HR 3.01, 95% CI 1.57-5.76; P = 0.001), and the net reclassification improvement
      was significant (15.2%, 95% CI 4.3-26%; P = 0.02). Time since completion of
      cancer treatment had an impact on the rate of TLR, with those patients with a
      current or recent cancer history having more TLR events within 1 year.
      Conclusion: We demonstrated a significant association between the recent history
      of cancer and the risk of recurrent coronary atherosclerosis in patients
      undergoing PCI and showed that malignancy status can predict the likelihood of
      cardiovascular events following this procedure.

PMID- 29211886
TI  - Bicarbonate induces high-level resistance to the human antimicrobial peptide LL
      37 in Staphylococcus aureus small colony variants.
AB  - Objectives: Staphylococcus aureus small colony variants (SCVs) cause persistent
      infections and are resistant to cationic antibiotics. Antimicrobial peptides
      (AMPs) have been suggested as promising alternatives for treating antibiotic
      resistant bacteria. We investigated the capacity of the human cationic AMP LL-37
      to kill SCVs in the presence of physiological concentrations of bicarbonate,
      which are reported to alter bacterial membrane permeability and change resistance
      of bacteria to AMPs. Methods: MBCs of LL-37 for S. aureus SCVs with mutations in
      different genes in the presence and absence of bicarbonate were determined.
      Results: In the absence of bicarbonate, SCVs of S. aureus strains LS-1 and 8325-4
      had the same level of resistance to LL-37 as the parental strain (8 mg/L). In the
      presence of bicarbonate, hemB, menD and aroD SCVs of LS-1 had high-level
      resistance to LL-37 (>=128 mg/L) compared with the parental strain (16 mg/L).
      However, only the aroD SCV of strain 8324-5 showed high-level resistance. 8325-4
      harbours mutations in two genes, tcaR and rsbU, which are involved in
      antimicrobial sensing and the stress response, respectively. When rsbU was
      repaired in 8325-4 it displayed high-level resistance to LL-37 in the presence of
      bicarbonate. This phenotype was lost when tcaR was also repaired, demonstrating
      that RsbU and TcaR are involved in LL-37 resistance in the presence of
      bicarbonate. Conclusions: S. aureus SCVs would be resistant to high
      concentrations of LL-37 in niches where there are physiological concentrations of
      bicarbonate and therefore this AMP may not be effective in combating SCVs.

PMID- 29211887
TI  - Genomic insights into the non-histamine production and proteolytic and lipolytic
      activities of Tetragenococcus halophilus KUD23.
AB  - Tetragenococcus halophilus KUD23, a non-histamine producer, was isolated from a
      traditional Korean high-salt fermented soybean paste, doenjang. The strain was
      safe in terms of antibiotic susceptibility, hemolytic activity and biofilm
      formation. It could grow on De Man-Rogosa-Sharpe agar containing 21% (w/v) NaCl,
      exhibited acid production at 15% NaCl, and had strain-specific proteolytic and
      lipolytic activities under salt stress. Complete genome analysis of T. halophilus
      KUD23 and comparative genomic analysis shed light on the genetic background
      behind these phenotypic characteristics, including non-production of histamine
      and proteolytic and lipolytic activities.

PMID- 29211888
TI  - Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and
      Severe Hirsutism: A Double-Blind Randomized Controlled Trial.
AB  - Context: Hirsutism often occurs in women with polycystic ovary syndrome (PCOS).
      The efficacy of oral contraceptive pill (OCP) plus antiandrogens in the treatment
      of its severe expression is controversial due to the lack of randomized, double
      blind, long-term studies. Objective: The primary outcome was the reduction of
      hirsutism in PCOS women objectively measured by videodermoscopy on the androgen
      sensitive skin areas assessed by the modified Ferriman and Gallwey (mF&G) total
      score, after 12 months of therapy with OCP + bicalutamide (BC) vs OCP plus
      placebo (P). The secondary outcomes were to evaluate tolerability of BC and body
      composition as well as the occurrence of adverse events. Design: An experimental,
      phase 3, prospective, multicenter, randomized, double-blind, P-controlled trial.
      Patients were evaluated at the baseline visit, at 6 and 12 months during
      treatment, and 6 months' posttreatment. Participants: Seventy women with classic
      PCOS (severe hirsutism, oligoanovulation, and ovarian polycystic ovarian
      morphology). Intervention: Patients received OCP + BC (50 mg/d) or OCP + P for 12
      months. Results: The repeated measures analysis of variance showed that both
      treatments were effective in reducing hirsutism: The OCP + BC group had a higher
      reduction compared with the OCP + P group. No adverse effects were described
      during treatment except an increase in total cholesterol and low-density
      lipoprotein in the OCP + BC group. Conclusions: The association of OCP + BC is
      well tolerated and significantly more effective than OCP alone in treating severe
      hirsutism. We suggest a combined use of the videodermoscopic index and mF&G to
      evaluate the effects of androgen deprivation therapy for hirsutism.

PMID- 29211889
TI  - Reduced live-birth rates after IVF/ICSI in women with previous unilateral
      oophorectomy: results of a multicentre cohort study.
AB  - STUDY QUESTION: Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment
      in women with a previous unilateral oophorectomy (UO)? SUMMARY ANSWER: A
      significantly reduced LBR after IVF/ICSI was found in women with previous UO when
      compared with women with intact ovaries in this large multicentre cohort, both
      crudely and after adjustment for age, BMI, fertility centre and calendar period
      and regardless of whether the analysis was based on transfer of embryos in the
      fresh cycle only or on cumulative results including transfers using frozen-thawed
      embryos. WHAT IS KNOWN ALREADY: Similar pregnancy rates after IVF/ICSI have been
      previously reported in case-control studies and small cohort studies of women
      with previous UO versus women without ovarian surgery. In all previous studies
      multiple embryos were transferred. No study has previously evaluated LBR in a
      large cohort of women with a history of UO. STUDY DESIGN, SIZE, DURATION: This
      research was a multicentre cohort study, including five reproductive medicine
      centres in Sweden: Carl von Linne Clinic (A), Karolinska University Hospital (B),
      Uppsala University Hospital (C), Linkoping University Hospital (D) and Orebro
      University Hospital (E). The women underwent IVF/ICSI between January 1999 and
      November 2015. Single embryo transfer (SET) was performed in approximately 70% of
      all treatments, without any significant difference between UO exposed women
      versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two
      embryos were transferred in the remaining cases. The dataset included all
      consecutive treatments and fresh and frozen-thawed cycles.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The exposed cohort included 154 women
      with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort
      consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the
      five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40
      treatments, respectively, and they were compared with controls of the same centre
      (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR,
      which was analysed per started cycle, per ovum pick-up (OPU) and per embryo
      transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and
      supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo
      quality scores and cumulative pregnancy rates. We used a Generalized Estimating
      Equation (GEE) model for statistical analysis in order to account for repeated
      treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control
      women's groups were comparable with regard to age and performance of IVF or ICSI.
      Significant differences in LBR, both crude and age-adjusted, were observed
      between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P =
      0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P
      = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025,
      respectively). The differences in LBR remained significant after inclusion of
      both fresh and frozen-thawed transfers (both crude and age-adjusted data):
      LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET
      (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude
      cancellation rate was significantly higher among women with a history of UO than
      in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a
      multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen
      thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen
      thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in
      the group of women with UO when adjusted for age, BMI, reproductive centre,
      calendar period and number of embryos transferred when appropriate. The OSI was
      significantly lower in women with a history of UO than in controls (3.6 versus
      6.0) and the difference was significant for both crude and age-adjusted data (P =
      <0.001 for both). Significantly fewer oocytes were retrieved in treatments of
      women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively).
      LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a
      retrospective analysis, with all its inherent limitations. Furthermore, the cause
      for UO was not possible to obtain in all cases. A diagnosis of endometriosis was
      also more common in the UO group, i.e. a selection bias in terms of poorer
      patient characteristics in the UO group cannot be completely ruled out. However,
      adjustment for all known confounders did not affect the general results. WIDER
      IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated
      and the first study indicating an association of achieving reduced live birth
      after IVF/ICSI in women with previous UO. These findings are novel and contradict
      the earlier notion that IVF/ICSI treatment is not affected, or is only marginally
      affected by previous UO. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 29211890
TI  - Effect of oregano oil and tannic acid combinations on the quality and sensory
      characteristics of cooked chicken meat.
AB  - The antioxidant effects of oregano essential oil and tannic acid combinations on
      ground chicken breast and thigh meats were studied. Six treatments, including: 1)
      control (none added), 2) 100 ppm oregano essential oil + 5 ppm tannic acid, 3)
      100 ppm oregano essential oil + 10 ppm tannic acid, 4) 200 ppm oregano essential
      oil + 5 ppm tannic acid, 5) 200 ppm oregano essential oil + 10 ppm tannic acid,
      and 6) 5 ppm butylated hydroxyanisole (BHA) for breast or 14 ppm for thigh meat,
      were prepared. Cooked meat samples were individually vacuum-packaged in oxygen
      impermeable vacuum bags and then cooked in-bag to an internal temperature of 75
      degrees C. After cooling to room temperature, the cooked meat was re-packaged in
      new oxygen-permeable bags and stored at 4 degrees C for 7 days. Cooked ground
      chicken meats were analyzed for lipid and protein oxidation and volatiles at 0,
      3, and 7 d of storage. The significant differences among the treatments were very
      clear in cooked meat samples: Thigh meat patties showed higher 2-thiobarbituric
      acid reactive substances (TBARS), total carbonyl, and volatiles content compared
      to the breast meat during storage. A combination of 200 ppm oregano oil with 10
      ppm tannic acid showed the most significant effects (P < 0.05) on TBARS, total
      carbonyl, and off-odor volatile formation for both breast and thigh meats.
      Oregano oil (200 ppm) and 10 ppm tannic acid combination also showed positive
      effects on the sensory scores of chicken thigh meat. In conclusion, the
      combination of 200 ppm oregano oil and 10 ppm tannic acid could be a good
      replacement for the synthetic antioxidants in ground cooked chicken meat.

PMID- 29211891
TI  - Osw2 is required for proper assembly of glucan and/or mannan layers of the yeast
      spore wall.
AB  - OSW2 is a meiotically-induced gene required for spore wall formation. osw2Delta
      spores are sensitive to ether treatment. Except for this phenotype, the mutants
      do not show obvious sporulation defects; thus, its function remains elusive. We
      found that deletion of both OSW2 and CHS3 results in a synthetic sporulation
      defect. The spore wall is composed of four layers, and chs3Delta spores lack the
      outer two (chitosan and dityrosine) layers. Thus, Osw2 is involved in the
      assembly of the inner (glucan and mannan) layers. In agreement with this notion,
      a glycosylphosphatidylinositol-anchored protein reporter mislocalizes in
      osw2Delta spores. The osw2Delta mutation also exhibited a severe synthetic
      sporulation defect when combined with the deletion of a beta-1,6-glucan synthesis
      related gene, BIG1. Osw2 is localized to the prospore membrane during
      sporulation. However, it disappears in mature spores, indicating that it is not a
      structural component of the spore wall. Given that Osw2 contains a probable 2
      dehydropantoate 2-reductase domain, it may mediate an enzymatic reaction. Osw2
      shows a weak similarity to other 2-dehydropantoate 2-reductase domain-containing
      proteins, Svl3 and Pam1. A pam1Deltasvl3Delta mutant exhibits vegetative cell and
      spore wall defects. Thus, the 2-dehydropantoate 2-reductase domain-containing
      proteins may have a similar function in glucan and/or mannan layer assembly.

PMID- 29211892
TI  - Evaluation of the effect of live LaSota Newcastle disease virus vaccine as
      primary immunization on immune development in broilers.
AB  - Newcastle disease remains a major concern to the poultry industry; however, it
      can be managed with effective vaccination programs. The main objective of this
      study was to evaluate the effect of 2 1* doses of live LaSota strain Newcastle
      disease virus (NDV) vaccine administered oculo-nasally on d one and 21 on
      development of humoral and cell-mediated immune response in broilers, and to
      compare different immunization schedules. Two experiments were conducted. In
      Experiment I (n = 320), Ross 308 birds were randomly assigned to an unvaccinated
      control group or vaccinated treatment. [Both treatments consisted of 4 pens per
      treatment and 40 birds per pen]. At d one, live NDV LaSota strain vaccine was
      used as a primary immunization to evaluate its impact on adaptive immunity. No
      substantial NDV-specific humoral immune response was established. Body weights
      were significantly higher (P < 0.05) in the vaccinated birds on d 4 and 7. Spleen
      index of the vaccinated birds was significantly (P < 0.05) lower at d 28 and 35.
      Flow cytometry showed reduced levels of peripheral and splenic B and T
      lymphocytes. Interferon gamma secreted by splenocytes and in circulation was
      measured; the results showed a reduced expression post-secondary immunization. In
      Experiment II (n = 180), the role of maternal antibodies and primary vaccination
      at d one was evaluated using 3 vaccination protocols. Protocol 1 used live B1
      strain as primary immunization, whereas protocol 2 used live LaSota strain.
      Protocol 3 used live LaSota strain after maternal antibodies had decayed.
      Protocol 3 resulted in the highest NDV-titer level during the trial. Protocol 2
      had the lowest NDV titer. Feed conversion was significantly higher (P < 0.05) in
      protocol 3 compared to 1 and 2. Overall, the results indicate that the use of
      live LaSota strain NDV vaccine as primary immunization at d one has a detrimental
      effect on the development of adaptive immunity in broilers; however, its use
      after the level of maternal antibodies decays results in a robust antigen
      specific humoral immune response.

PMID- 29211894
TI  - Acid growth: an ongoing trip.
AB  - Since its first formulation almost 50 years ago, acid growth has had a chequered
      past complicated by utilization of diverse species and organs for testing
      alongside necessary but coarse methodology. Within the past 25 years, we have
      gained new insights into the molecular mechanisms behind the transduction of the
      signal auxin into the reality of an apoplastic pH shift as well as the effect on
      cell wall mechanics and the biochemical players within the wall contributing to
      the resultant growth. In this review, we begin by discussing the historical work
      and its complications, move on to the modern work and its addition to acid
      growth, which we finally summarize in an updated model which includes new
      postulations and questions.

PMID- 29211893
TI  - Aldosterone Is Not Associated With Metabolic and Microvascular Insulin
      Sensitivity in Abdominally Obese Men.
AB  - Context: Impaired insulin-mediated muscle microvascular recruitment (IMMR) may
      add to the development of insulin resistance and hypertension. Increased
      aldosterone levels have been linked to these obesity-related complications in
      severely to morbidly obese individuals and to impaired microvascular function in
      experimental studies. Objectives: To investigate whether aldosterone levels are
      associated with IMMR, insulin sensitivity, and blood pressure in lean and
      moderately abdominally obese men, and to study the effect of weight loss. Design,
      Setting, Participants, Intervention, Main Outcome Measures: In 25 lean and 53
      abdominally obese men, 24-hour blood pressure measurement was performed, and
      aldosterone levels were measured using ultra-performance liquid chromatography
      tandem mass spectrometry. Insulin sensitivity was assessed by determining whole
      body glucose disposal during a hyperinsulinemic clamp. IMMR in forearm skeletal
      muscle was measured with contrast-enhanced ultrasonography. These assessments
      were repeated in the abdominally obese men following an 8-week weight loss or
      weight stable period. Results: Sodium excretion and aldosterone levels were
      similar in lean and abdominally obese participants, but sodium excretion was
      inversely associated with aldosterone concentration only in the lean individuals
      [lean, beta/100 mmol sodium excretion (adjusted for age and urinary potassium
      excretion) = -0.481 (95% confidence interval, -0.949 to -0.013); abdominally
      obese, beta/100 mmol sodium excretion = -0.081 (95% confidence interval, -0.433
      to 0.271); P for interaction = 0.02]. Aldosterone was not associated with IMMR,
      insulin sensitivity, or blood pressure and was unaffected by weight loss.
      Conclusion: In moderately abdominally obese men, the inverse relationship between
      sodium excretion and aldosterone concentration is less than that in lean men but
      does not translate into higher aldosterone levels. The absolute aldosterone level
      does not explain differences in microvascular and metabolic insulin sensitivity
      and blood pressure between lean and moderately abdominally obese men.

PMID- 29211895
TI  - Review of environmental enrichment for broiler chickens.
AB  - Welfare problems are commonly found in both conventional and organic production
      of broiler chickens. In order to reduce the extent of welfare problems, it has
      been suggested to provide stimulating, enriched environments. The aim of the
      present paper is to provide a review of the effect on behavior and welfare of the
      different kinds of environmental enrichments in the production of broilers that
      have been described in the scientific literature. Environmental enrichment is
      defined as an improvement of the environment of captive animals, which increases
      the behavioral opportunities of the animal and leads to improvements of the
      biological function. This definition has been broadened to include practical and
      economic aspects, as any enrichment strategy that adversely affects the health of
      animals or that has too many economic or practical constraints will never be
      implemented on commercial farms and thus never benefit animals. Environmental
      enrichment for broilers often has the purpose of satisfying behavioral needs
      and/or stimulating the broilers to an increased level of activity, which among
      others will reduce the occurrence of leg problems. Potentially successful
      environmental enrichments for broiler chickens are elevated resting-places,
      panels, barriers, and bales of straw ("point-source enrichment"), as well as
      covered verandas and outdoor ranges ("complex enriched environments"). Many of
      the ideas for environmental enrichment for broilers need to be further developed
      and studied, preferably in commercial trials, with respect to the use, the effect
      on behavior and on other welfare aspects such as leg health, and the interaction
      with genotype, production system, stocking density, light, and flock size. In
      addition, information on the practical application and the economics of the
      production system is often lacking, although it is important for application in
      practice.

PMID- 29211896
TI  - Letter: Contralateral Anterior Interhemispheric Approach to Medial Frontal
      Arteriovenous Malformations: Surgical Technique and Results.

PMID- 29211897
TI  - Effect of yeast cell wall on the growth performance and gut health of broilers
      challenged with aflatoxin B1 and necrotic enteritis.
AB  - This study aimed to investigate the effect of yeast cell walls (YCW) on the
      growth performance, visceral lesions, intestinal integrity, enterotoxicity, and
      bacteria of broilers challenged with aflatoxin B1 (AF) and necrotic enteritis
      (NE) from 1 to 21 d of age. A total of 576 one-day-old broilers were assigned to
      a 2 * 2 * 2 design for diets containing AFB1 (0 or 40 MUg/kg), NE (challenged or
      unchallenged), or YCW (0 or 500 mg/kg). The main effect analysis showed that AF
      depressed (P < 0.01) average daily feed intake (ADFI), average daily body weight
      gain (ADG), the mRNA profiles of polymeric Ig receptor (pIgR), claudin-1, and
      occludin, but increased (P < 0.001) liver lesion scores, serum endotoxin, and
      diamine oxidase (DAO). The NE challenge depressed (P < 0.01) ADFI, ADG, secretory
      IgA (sIgA), pIgR, claudin-1, occludin, and the populations of Lactobacilli and
      Bifidobacteria, but increased (P < 0.001) visceral lesions, endotoxins, and DAO.
      The main effect of YCW on growth performance, visceral lesions, and intestinal
      integrity was not significant, but decreased (P < 0.01) mortality, endotoxin,
      DAO, and C. perfringens, and increased (P < 0.05) the populations of Lactobacilli
      and Bifidobacteria. There were 3-way interactions (P < 0.05) on growth
      performance, intestinal lesions, integrity, and gut bacteria. Compared with the
      treatment with the dual challenges, there were pronounced effects (P < 0.05) of
      YCW on ADFI, ADG, lesions, DAO, pIgR, and Bifidobacteria. The results suggest
      that with the concurrent challenges of AF and NE, the YCW can partially protect
      the growth performance and intestinal health of broilers.

PMID- 29211898
TI  - Bilateral upper lobe Pneumocystis pneumonia during aerosolized pentamidine
      prophylaxis.

PMID- 29211899
TI  - Exome Sequencing and Genotyping Identify a Rare Variant in NLRP7 Gene Associated
      With Ulcerative Colitis.
AB  - Background and Aims: Although genome-wide association studies [GWAS] in
      inflammatory bowel disease [IBD] have identified a large number of common disease
      susceptibility alleles for both Crohn's disease [CD] and ulcerative colitis [UC],
      a substantial fraction of IBD heritability remains unexplained, suggesting that
      rare coding genetic variants may also have a role in pathogenesis. We used high
      throughput sequencing in families with multiple cases of IBD, followed by
      genotyping of cases and controls, to investigate whether rare protein-altering
      genetic variants are associated with susceptibility to IBD. Methods: Whole-exome
      sequencing was carried out in 10 families in whom three or more individuals were
      affected with IBD. A stepwise filtering approach was applied to exome variants,
      to identify potential causal variants. Follow-up genotyping was performed in 6025
      IBD cases [2948 CD; 3077 UC] and 7238 controls. Results: Our exome variant
      analysis revealed coding variants in the NLRP7 gene that were present in affected
      individuals in two distinct families. Genotyping of the two variants, p.S361L and
      p.R801H, in IBD cases and controls showed that the p.S361L variant was
      significantly associated with an increased risk of ulcerative colitis [odds ratio
      4.79, p = 0.0039] and IBD [odds ratio 3.17, p = 0.037]. A combined analysis of
      both variants showed suggestive association with an increased risk of IBD [odds
      ratio 2.77, p = 0.018]. Conclusions: The results suggest that NLRP7 signalling
      and inflammasome formation may be a significant component in the pathogenesis of
      IBD.

PMID- 29211901
TI  - CORRIGENDUM FOR "Low-Dose Dihydrotestosterone Drives Metabolic Dysfunction via
      Cytosolic and Nuclear Hepatic Androgen Receptor Mechanisms".

PMID- 29211902
TI  - Leptin Effects on DAT Neurons To Control Energy Homeostasis.

PMID- 29211900
TI  - Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled
      analysis of 12 case-control studies.
AB  - Background: Ovarian cancer incidence differs substantially by race/ethnicity, but
      the reasons for this are not well understood. Data were pooled from the African
      American Cancer Epidemiology Study (AACES) and 11 case-control studies in the
      Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences
      in epidemiological characteristics with suspected involvement in epithelial
      ovarian cancer (EOC) aetiology. Methods: We used multivariable logistic
      regression to estimate associations for 17 reproductive, hormonal and lifestyle
      characteristics and EOC risk by race/ethnicity among 10 924 women with invasive
      EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific
      Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233
      Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to
      evaluate heterogeneity in the risk factor associations by race/ethnicity.
      Results: We observed statistically significant racial/ethnic heterogeneity for
      hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was
      observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02]
      compared with other racial/ethnic groups. Although not statistically significant,
      the associations for parity, first-degree family history of ovarian or breast
      cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had
      the greatest magnitude of association for parity (>=3 births: OR = 0.38, 95% CI =
      0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77,
      95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55).
      Conclusions: Although racial/ethnic heterogeneity was observed for hysterectomy,
      our findings support the validity of EOC risk factors across all racial/ethnic
      groups, and further suggest that any racial/ethnic population with a higher
      prevalence of a modifiable risk factor should be targeted to disseminate
      information about prevention.

PMID- 29211903
TI  - Reflections on Endocrinology, 2013-2017.

PMID- 29211906
TI  - Of Time and the River: How Our Understanding of Legionellosis Has Changed Since
      1976.

PMID- 29211904
TI  - Associations between genetic variants associated with body mass index and
      trajectories of body fatness across the life course: a longitudinal analysis.
AB  - Background: The genetic associations with trajectories of body fatness over the
      life course remain unknown. Methods: We used a group-based modelling approach to
      identify trajectories of body fatness from age 5 years up to 65 for 7277 women
      from the Nurses' Health Study and 4645 men from the Health Professionals Follow
      up Study. We created a genetic risk score (GRS) based on 97 variants associated
      with adulthood body mass index (BMI) and estimated its association with
      trajectories using logistic regression. Results: We identified four distinct
      trajectories: lean-medium, medium-medium, lean-heavy and medium-heavy. The GRS
      increased across the four groups in that order (P < 0.001); 47% of women and 45%
      of men in the first decile of the GRS were in the lean-medium group, and these
      proportions reduced to 26% and 28%, respectively, for the highest decile. The
      corresponding proportions in the medium-heavy group were 8% and 5%, increasing to
      21% and 14%, respectively. For women, compared with the odds of being in the lean
      medium group, a 10-allele increment in the GRS was associated with a 40% [95%
      confidence interval (CI), 27-54%], 43% (30-58%), and 115% (91-143%) increase in
      the odds of being in the medium-medium, lean-heavy and medium-heavy groups,
      respectively. For men, the corresponding increases in the odds were 26% (12-42%),
      27% (13-43%), and 81% (53-115%), respectively. Conclusions: Individuals with
      genetic variants for adulthood BMI were more likely to maintain a heavy body
      shape and gain weight throughout life. These findings support a persistent effect
      of genetic variants on body fatness across the lifespan.

PMID- 29211905
TI  - Effect of different concentrations of dietary P and Ca on plasma inorganic P and
      urinary P excretion using noncolostomized and colostomized broilers.
AB  - Two 5-d bioassays were conducted to explore the P physiological threshold in
      broilers based on plasma inorganic P (iP), urinary P and Ca, and excreta P and Ca
      measurements in non-colostomized and colostomized broilers fed with different
      concentrations of non-phytate P (NPP) and Ca. In Experiment 1, 80 40-day-old Cobb
      500 non-colostomized male broilers were assorted into 8 groups consisting of 10
      broilers each and placed in individual metabolic cages. Similarly, 8 colostomized
      broilers of same age were allotted to 8 individual metabolic cages. The
      experimental diets consisted of a corn soybean meal basal containing 0.17%
      phytate P (PP) with 8 concentrations (0.08, 0.13, 0.18, 0.23, 0.28, 0.33, 0.38,
      and 0.45%) of NPP. The dietary Ca concentration was maintained at 0.5% by
      adjusting a 185-micron particle size limestone with each concentration of added P
      from added calcium phosphate, dibasic, monohydrate. After Experiment 1, broilers
      were fed a standard grower diet for 5 d and Experiment 2 was conducted the same
      as Experiment 1; however, Ca was maintained at 0.9% for all test diets. Plasma
      iP, urinary P and Ca, and total P (TP) and Ca retention along with phytate P
      hydrolysis were measured. At 0.5% Ca dietary level, the inflection points for
      dietary NPP obtained from segmented line regression analysis for plasma iP,
      urinary P, and urinary Ca were 0.26% (+/-0.04 SE), 0.28% (+/-0.01 SE), and 0.30%
      (+/-0.04 SE), respectively. The similar values for 0.9% Ca diets were 0.27% (+/
      0.03 SE), 0.21% (+/-0.03 SE), and 0.30% (+/-0.0 SE), respectively. In summary,
      the present findings suggest that an increased dietary NPP would increase plasma
      inorganic P concentration along with increased % retention of TP and NPP until
      the broilers reach a point of physiological steady state (7.51 mg iP/dL - 8.13 mg
      iP/dL as found in this study). Excess P beyond physiological threshold is
      eliminated in urine coupled with decreased % retention.

PMID- 29211907
TI  - Evaluation of the hygienogram scores and related data obtained after cleaning and
      disinfection of poultry houses in Flanders during the period 2007 to 2014.
AB  - Cleaning and disinfection (C&D) of poultry houses is an essential aspect in farm
      hygiene management. Adequate performance of the different steps of a C&D protocol
      and the use of suitable products are key to prevent and control zoonoses and
      animal diseases. Hygiene monitoring on total aerobic flora through sampling with
      agar contact plates at different locations of the poultry house results in a
      hygienogram score that is used to evaluate the proper execution of C&D.This study
      analyzed the hygienogram scores of 19,739 poultry flocks in Flanders after C&D.
      Data relating to the C&D protocol, i.e., year, season, husbandry system,
      production type, cleaning product, sampler, active components of the
      disinfectant, disinfection time, disinfection temperature, and disinfection
      responsible, were collected.The average hygienogram score decreased significantly
      over time, suggesting a general improvement between 2007 and 2014. Differences in
      scores were found among the husbandry systems, with the barn/aviary system having
      a significantly better hygienogram score compared to the floor house, furnished
      cage, and battery. Significantly better scores also were found when a cleaning
      product was used in the C&D protocol. Disinfection with a peracetic acid and
      hydrogen peroxide combination or formaldehyde gave the best scores. In addition,
      C&D protocols using >=2 different disinfectants showed improved results compared
      to the use of one single disinfectant. Finally, disinfection applied by a
      specialist contractor resulted in a better score compared to disinfection by the
      farmer.In conclusion, analysis of the hygienogram scores and related data allowed
      identifying several factors, resulting in an improvement, which may reduce the
      total bacterial load in poultry stables and, consequently, the number of zoonotic
      and pathogenic micro-organisms.

PMID- 29211908
TI  - Occupational health and safety in the Southern African Development Community.

PMID- 29211909
TI  - Why work is so problematic for people with disabilities and long-term health
      problems.

PMID- 29211910
TI  - Bringing together occupational and environmental medicine specialists:
      Development of the International Occupational Medicine Society Collaborative
      (IOMSC).

PMID- 29211911
TI  - Blood transfusions-more is not better.

PMID- 29211912
TI  - Intestinal T Cell Profiling in Inflammatory Bowel Disease: Linking T Cell Subsets
      to Disease Activity and Disease Course.
AB  - Introduction: A dysregulated intestinal T cell response is presumed in patients
      with inflammatory bowel disease [IBD]. In this longitudinal study, we
      investigated the changes in intestinal T lymphocyte subsets in IBD at first
      presentation and over time during endoscopic active or inactive disease, and
      relate them to disease activity and outcome. Methods: We included 129 newly
      diagnosed patients (87 Crohn's disease [CD], 42 ulcerative colitis [UC]) and 19
      healthy controls [HC]. Follow-up biopsy specimens were analysed from 70 IBD
      patients. Immunophenotyping of specimens was performed by flow cytometry
      identifying lymphocyte subpopulations. Results: IBD patients at diagnosis
      displayed higher percentages of CD4 T+ cells, Tregs, and central memory T cells
      [TCM] and with lower percentages of CD8 and CD103 T lymphocytes than HC. Follow
      up specimens of patients with endoscopic inactive disease showed T cell subset
      recovery comparable to HC. Endoscopic active disease at follow-up coincided with
      T cell subsets similar to those at diagnosis. In UC, lower baseline percentages
      of CD3 cells was associated with milder disease course without the need of an
      immunomodulator, whereas in CD, higher baseline percentages of CD4 and Tregs were
      associated with complicated disease course. Conclusions: The intestinal T cell
      infiltrate in IBD patients with active endoscopic disease is composed of
      increased percentages of CD4+ T cells, Tregs, and TCM, with lower percentages of
      CD8+ T cells and CD103+ T cells, compared with HC and endoscopic inactive IBD.
      Baseline percentages of CD3, CD4, and Tregs were associated with disease outcome.
      Further research is needed to demonstrate the predictive value of these
      lymphocyte subsets.

PMID- 29211913
TI  - Single-centre study of therapeutic drug monitoring of posaconazole in lung
      transplant recipients: factors affecting trough plasma concentrations.
AB  - Objectives: This study describes therapeutic drug monitoring (TDM) of
      posaconazole suspension and modified release (MR) tablets in lung transplant
      (LTx) recipients and evaluates factors that may affect posaconazole trough plasma
      concentration (Cmin). Methods: A single-centre, retrospective study evaluating
      posaconazole Cmin in LTx recipients receiving posaconazole suspension or MR
      tablets between January 2014 and December 2016. Results: Forty-seven LTx patients
      received posaconazole suspension, and 78 received the MR tablet formulation; a
      total of 421 and 617 Cmin measurements were made, respectively. Posaconazole was
      concurrently administered with proton pump inhibitor in >= 90% of patients. The
      median (IQR) of initial posaconazole Cmin following 300 mg daily of posaconazole
      tablet was significantly higher than that of 800 mg daily of posaconazole
      suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P < 0.01].
      Variability in posaconazole Cmin was apparent regardless of the formulations
      prescribed and dose adjustments were routinely undertaken to maintain therapeutic
      Cmin. A clear dose-response relationship was observed in patients receiving
      posaconazole MR tablets. Non-specific adverse events (fatigue, tremor, lethargy,
      sweating, nausea/vomiting and weight loss) were reported in 3/78 (4%) patients
      receiving posaconazole MR tablets. Posaconazole Cmin in these three patients was
      determined to be 9.6, 6.2 and 2.3 mg/L. Conclusions: The current study has
      provided clinically important insights into the TDM of posaconazole in LTx
      recipients. Routine TDM should be undertaken in LTx recipients receiving
      posaconazole suspension and/or MR tablets.

PMID- 29211915
TI  - Reply.

PMID- 29211914
TI  - Stinging nettle and neem enhance antibody response to local killed and imported
      live infectious bursal disease vaccines in indigenous chicken in Kenya.
AB  - Immune responses are critical for protection of chickens from infectious bursal
      disease (IBD). In this study, the antibody response-enhancing effect of drinking
      water supplementation of 1% stinging nettle and neem on different IBD vaccines
      and vaccination regimes was evaluated, using 36 (n = 36) specific antibody
      negative indigenous chicks. The birds were allocated into 3 groups as follows: 1A
      C, 2A-C, and 3A-B, while group 3C acted as the unvaccinated non-supplemented
      control. A local inactivated K1 and imported live attenuated D78 IBD vaccines
      were given to groups 1A-C and 3A-B at 14 and 28 d of age, respectively. A
      combination of K1 and D78 vaccines was given 30 d apart to groups 2A and 2B (D78
      at 14 and 21 d and K1 at 44 d of age) and on the same d to group 2C at 14 and 28
      d of age. Stinging nettle was given in water to groups 1B, 2B, and 2C, and neem
      to groups 1C, 2A, and 3B. Birds were bled weekly and immune responses monitored
      using indirect ELISA. Both neem and stinging nettle had antibody response
      enhancing effects in groups 1B and 1C, receiving the local inactivated K1
      vaccine. There were significant differences (P < 0.05) in antibody titers between
      groups 1A and 2C. Stinging nettle induced earlier onset of high antibody
      responses in group 2C and persistent titers (>3.8 log10) from the third week in
      group 2B. Imported live D78 vaccine induced higher antibody titers compared to
      the local inactivated K1 vaccine. Groups 2B and 2C receiving a combination of the
      local K1 and imported live attenuated D78 vaccines had the highest antibody
      titers. Adoption of stinging nettle supplementation and a prime-boost program
      involving use of a local virus isolates-derived vaccine is recommended.

PMID- 29211916
TI  - Feasibility of 7T MRI for imaging fascicular structures of peripheral nerves.
AB  - INTRODUCTION: Evaluation of the nerve fascicular structure can be useful in
      diagnosing nerve damage, but it is a very challenging task with 3T MRI because of
      limited resolution. In this pilot study, we present the feasibility of high
      resolution 7T MRI for examining the nerve fascicular structure. METHODS: A 3
      dimensional (3D) gradient-spoiled sequence was used for imaging peripheral nerves
      in extremities. Images acquired with different in-plane resolutions (0.42 * 0.42
      mm vs. 0.12 * 0.12 mm), and different main field strengths (7T vs. 3T) were
      compared. RESULTS: The individual nerve fascicles were identified at 0.12 * 0.12
      mm resolution in both field strengths but not at 0.42 * 0.42 mm resolution. The
      fascicular structure was more sharply depicted in 7T images than in 3T images.
      DISCUSSION: High-resolution 3D imaging with 7T MRI demonstrated feasibility for
      imaging nerve fascicular structures. Muscle Nerve 57: 494-498, 2018.

PMID- 29211917
TI  - Quantifying Cancer Risk from Radiation.
AB  - Complex statistical models fitted to data from studies of atomic bomb survivors
      are used to estimate the human health effects of ionizing radiation exposures. We
      describe and illustrate an approach to estimate population risks from ionizing
      radiation exposure that relaxes many assumptions about radiation-related
      mortality. The approach draws on developments in methods for causal inference.
      The results offer a different way to quantify radiation's effects and show that
      conventional estimates of the population burden of excess cancer at high
      radiation doses are driven strongly by projecting outside the range of current
      data. Summary results obtained using the proposed approach are similar in
      magnitude to those obtained using conventional methods, although estimates of
      radiation-related excess cancers differ for many age, sex, and dose groups. At
      low doses relevant to typical exposures, the strength of evidence in data is
      surprisingly weak. Statements regarding human health effects at low doses rely
      strongly on the use of modeling assumptions.

PMID- 29211919
TI  - Myofibrillar myopathy due to dominant LMNA mutations: A report of 2 cases.

PMID- 29211918
TI  - Decellularized human placenta supports hepatic tissue and allows rescue in acute
      liver failure.
AB  - : Tissue engineering with scaffolds to form transplantable organs is of wide
      interest. Decellularized tissues have been tested for this purpose, although
      supplies of healthy donor tissues, vascular recellularization for perfusion, and
      tissue homeostasis in engineered organs pose challenges. We hypothesized that
      decellularized human placenta will be suitable for tissue engineering. The
      universal availability and unique structures of placenta for accommodating
      tissue, including presence of embedded vessels, were major attractions. We found
      decellularized placental vessels were reendothelialized by adjacent native cells
      and bridged vessel defects in rats. In addition, implantation of liver fragments
      containing all cell types successfully hepatized placenta with maintenance of
      albumin and urea synthesis, as well as hepatobiliary transport of 99m Tc
      mebrofenin, up to 3 days in vitro. After hepatized placenta containing autologous
      liver was transplanted into sheep, tissue units were well-perfused and self
      assembled. Histological examination indicated transplanted tissue retained
      hepatic cord structures with characteristic hepatic organelles, such as gap
      junctions, and hepatic sinusoids lined by endothelial cells, Kupffer cells, and
      other cell types. Hepatocytes in this neo-organ expressed albumin and contained
      glycogen. Moreover, transplantation of hepatized placenta containing autologous
      tissue rescued sheep in extended partial hepatectomy-induced acute liver failure.
      This rescue concerned amelioration of injury and induction of regeneration in
      native liver. The grafted hepatized placenta was intact with healthy tissue that
      neither proliferated nor was otherwise altered. CONCLUSION: The unique anatomic
      structure and matrix of human placenta were effective for hepatic tissue
      engineering. This will advance applications ranging from biological studies, drug
      development, and toxicology to patient therapies. (Hepatology 2018;67:1956-1969).

PMID- 29211920
TI  - Miconazole enhances nerve regeneration and functional recovery after sciatic
      nerve crush injury.
AB  - INTRODUCTION: Improving axonal outgrowth and remyelination is crucial for
      peripheral nerve regeneration. Miconazole appears to enhance remyelination in the
      central nervous system. In this study we assess the effect of miconazole on
      axonal regeneration using a sciatic nerve crush injury model in rats. METHODS:
      Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve
      regeneration and myelination were determined using histological and
      electrophysiological assessment. Evaluation of sensory and motor recovery was
      performed using the pinprick assay and sciatic functional index. The Cell
      Counting Kit-8 assay and Western blotting were used to assess the proliferation
      and neurotrophic expression of RSC 96 Schwann cells. RESULTS: Miconazole promoted
      axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and
      walking behavior, enhanced stimulated amplitude and nerve conduction velocity,
      and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells.
      DISCUSSION: Miconazole was beneficial for nerve regeneration and functional
      recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018.

PMID- 29211922
TI  - Local blood flow in peripheral nerves and their ganglia: Resurrecting key ideas
      around its measurement and significance.
AB  - Over 3 decades ago, seminal work by Phillip Low and colleagues established
      exquisite physiology around the measurement of nerve blood flow (NBF). Although
      not widely explored recently, its connection to the clinic has awaited human
      methodology. While human studies have not achieved a convincing level of rigour,
      newer imaging technologies are offering early information. The peripheral nerve
      trunk has parallel blood flow compartments that include epineurial flow dominated
      by arteriovenous shunts and downstream endoneurial blood flow (EBF). NBF and EBF
      have lower values than central nervous system blood flow, lack autoregulation yet
      have sympathetic and peptidergic neurovascular control. Contrary to expectation,
      injury to nerves is often associated with rises in NBF rather than ischemia, a
      finding of biological interest corroborated by human studies. Despite its
      potential importance, quantitative human measurements of EBF and NBF are not yet
      available. However, with development, careful NBF analysis may present new
      insights into nerve disorders. Muscle Nerve 57: 884-895, 2018.

PMID- 29211921
TI  - Infections and the relationship to treatment in neuromuscular autoimmunity.
AB  - INTRODUCTION: This study aimed to identify infections in patients with myasthenia
      gravis, dermatomyositis, and chronic inflammatory demyelinating
      polyradiculoneuropathy, and to investigate the relationship between infection and
      immunomodulation. METHODS: A retrospective chart review examined 631 patients
      with myasthenia gravis (n = 358), chronic inflammatory demyelinating
      polyradiculoneuropathy (n = 124), and dermatomyositis (n = 149) patients over a
      10-year time period. RESULTS: Infection rates were similar at approximately 19%
      in all 3 diseases. Of the infections in which a causative organism was
      identified, pneumonia, sepsis, and opportunistic infections were the leading
      diagnoses. A multivariate model demonstrated a significant association between
      infection and an increased dose of plasma exchange, mycophenolate mofetil, and
      corticosteroid therapy. DISCUSSION: There are few large studies investigating
      rates of infections in patients with autoimmune neuromuscular disorders and the
      relationship to immunomodulation. This study not only demonstrates the remarkably
      similar infection rates across the 3 diseases studied, but also shows their
      relationship to commonly used immunotherapies. Muscle Nerve 57: 927-931, 2018.

PMID- 29211923
TI  - Xylem hydraulic safety and construction costs determine tropical tree growth.
AB  - Faster growth in tropical trees is usually associated with higher mortality
      rates, but the mechanisms underlying this relationship are poorly understood. In
      this study, we investigate how tree growth patterns are linked with environmental
      conditions and hydraulic traits, by monitoring the cambial growth of 9 tropical
      cloud forest tree species coupled with numerical simulations using an
      optimization model. We find that fast-growing trees have lower xylem safety
      margins than slow-growing trees and this pattern is not necessarily linked to
      differences in stomatal behaviour or environmental conditions when growth occurs.
      Instead, fast-growing trees have xylem vessels that are more vulnerable to
      cavitation and lower density wood. We propose the growth - xylem vulnerability
      trade-off represents a wood hydraulic economics spectrum similar to the classic
      leaf economic spectrum, and show through numerical simulations that this trade
      off can emerge from the coordination between growth rates, wood density, and
      xylem vulnerability to cavitation. Our results suggest that vulnerability to
      hydraulic failure might be related with the growth-mortality trade-off in
      tropical trees, determining important life history differences. These findings
      are important in furthering our understanding of xylem hydraulic functioning and
      its implications on plant carbon economy.

PMID- 29211924
TI  - ANATOLIA: NMR software for spectral analysis of total lineshape.
AB  - Evolution of the theoretical spectrum during the course of spectrum analysis and
      comparison of the result with the experimental spectrum.

PMID- 29211925
TI  - Artificial neural networks and liver transplantation: Are we ready for self
      driving cars?

PMID- 29211926
TI  - Heterotelechelic Polymers by Ring-Opening Metathesis and Regioselective Chain
      Transfer.
AB  - Heterotelechelic polymers were synthesized by a kinetic telechelic ring-opening
      metathesis polymerization method relying on the regioselective cross-metathesis
      of the propagating Grubbs' first-generation catalyst with cinnamyl alcohol
      derivatives. This procedure allowed the synthesis of hetero-bis-end-functional
      polymers in a one-pot setup. The molecular weight of the polymers could be
      controlled by varying the ratio between cinnamyl alcohol derivatives and monomer.
      The end functional groups can be changed using different aromatically substituted
      cinnamyl alcohol derivatives. Different monomers were investigated and the
      presence of the functional groups was shown by NMR spectroscopy and MALDI-ToF
      mass spectrometry. Labeling experiments with dyes were conducted to demonstrate
      the orthogonal addressability of both chain ends of the heterotelechelic polymers
      obtained.

PMID- 29211927
TI  - Cleavage of Unstrained C-C Bonds in Acenes by Boron and Light: Transformation of
      Naphthalene into Benzoborepin.
AB  - Naphthalene and acenaphthene with peri 2-py and BMes2 (py=pyridyl, Mes=mesityl)
      substituents have been found to undergo facile phototransformation, cleavage of a
      C-C bond of naphthalene, and formation of 2-py-bound benzoborepins as the major
      products. Mechanistic pathways of this photoreaction have been established by
      examination of both excited and ground states by using CASSCF and CASPT2 methods
      in DFT and time-dependent DFT calculations. The mesityl to py-naphthyl charge
      transfer transition and the mesityl migration from the boron atom to the naphthyl
      moiety drive this unprecedented C-C bond cleavage and boron-insertion reaction.

PMID- 29211928
TI  - Effect of tannic acid on skin barrier function.
AB  - In this study, we investigated how tannic acid (TA) protects the skin from
      inflammation caused by external irritation. The effects of TA were evaluated
      using a mouse 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin
      inflammation model and a reconstructed human epidermal model. We then used
      Lucifer Yellow for visual confirmation of TA's suppression effect at the stratum
      corneum (SC) surface. TA treatment of the skin prevented Lucifer Yellow from
      permeating the skin. This result suggests that TA acts as a barrier against
      external stimulants such as TPA and artificial sweat on the SC surface.

PMID- 29211929
TI  - Further Studies on How the Nature of Zeolite Cavities That Are Bounded by Small
      Pores Influences the Conversion of Methanol to Light Olefins.
AB  - A series of small-pore zeolites are synthesized and investigated as catalysts for
      the methanol-to-olefins (MTO) reaction. Small-pore zeolites SSZ-13, SSZ-16, SSZ
      27, SSZ-28, SSZ-52, SSZ-98, SSZ-99, SSZ-104, SSZ-105 and an ITQ-3-type material
      are synthesized, and the results from their use as catalytic materials in the MTO
      reaction compared to those obtained from SAPO-34. The production of propane that
      tends to correlate with catalytic material lifetime (higher initial propane
      yields lead to shorter lifetimes) declines with increasing Si/Al (as has been
      observed previously for SSZ-13), and a larger cage dimension leads to higher
      propane yields at a fixed Si/Al. Data from these materials and others reported
      previously, for example, SSZ-39 and Rho, that were tested at the same reaction
      conditions, revealed four different patterns of light olefin selectivities: 1)
      ethylene greater than propylene with low butene, for example, SSZ-17, SSZ-98, SSZ
      105, 2) ethylene equal to propylene and low butene, for example, SAPO-34, SSZ-13,
      SSZ-16, SSZ-27, SSZ-52, SSZ-99, SSZ-104, 3) propylene greater than ethylene with
      butene similar to ethylene, for example, SSZ-28, SSZ-39, and 4) ethylene equal to
      propylene equal to butene, for example, Rho. No clear relationships between
      zeolite cage architecture and light olefin selectivity emerged from this
      investigation, although several trends are presented as suggestions for further
      study.

PMID- 29211930
TI  - Estimating the global prevalence of transthyretin familial amyloid
      polyneuropathy.
AB  - INTRODUCTION: This study sought to estimate the global prevalence of
      transthyretin familial amyloid polyneuropathy (ATTR-FAP). METHODS: Prevalence
      estimates and information supporting prevalence calculations was extracted from
      records yielded by reference-database searches (2005-2016), conference
      proceedings, and nonpeer reviewed sources. Prevalence was calculated as
      prevalence rate multiplied by general population size, then extrapolated to
      countries without prevalence estimates but with reported cases. RESULTS: Searches
      returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding
      prevalence for 10 "core" countries, then extrapolated to 32 additional countries.
      ATTR-FAP prevalence in core countries, extrapolated countries, and globally was
      3,762 (range 3639-3884), 6424 (range, 1,887-34,584), and 10,186 (range, 5,526
      38,468) persons, respectively. DISCUSSION: The mid global prevalence estimate
      (10,186) approximates the maximum commonly accepted estimate (5,000-10,000). The
      upper limit (38,468) implies potentially higher prevalence. These estimates
      should be interpreted carefully because contributing evidence was heterogeneous
      and carried an overall moderate risk of bias. This highlights the requirement for
      increasing rare-disease epidemiological assessment and clinician awareness.
      Muscle Nerve 57: 829-837, 2018.

PMID- 29211931
TI  - The role of microsomal epoxide hydrolase, Na+ -taurocholate cotransporting
      polypeptide, and organic anion transporting polypeptide in hepatic sodium
      dependent bile acid transport.

PMID- 29211932
TI  - Targeted vs systematic robot-assisted transperineal magnetic resonance imaging
      transrectal ultrasonography fusion prostate biopsy.
AB  - OBJECTIVE: To evaluate the performance of transperineal robot-assisted (RA)
      targeted (TB) and systematic (SB) prostate biopsy in primary and repeat biopsy
      settings. PATIENTS AND METHODS: Patients underwent RA biopsy between 2014 and
      2016. Before RA-TB, multiparametric magnetic resonance imaging (mpMRI) was
      performed. Prostate lesions were scored (Prostate Imaging, Reporting and Data
      System, version 2) and used for RA-TB planning. In addition, RA-SB was performed.
      Available, whole-gland pathology was analysed. RESULTS: In all, 130 patients were
      biopsy naive and 72 had had a previous negative transrectal ultrasonography
      guided biopsy. In total, 202 patients had suspicious mpMRI lesions. Clinically
      significant prostate cancer was found in 85% of all prostate cancer cases (n =
      123). Total and clinically significant prostate cancer detection rates for RA-TB
      vs RA-SB were not significantly different at 77% vs 84% and 80% vs 82%,
      respectively. RA-TB demonstrated a better sampling performance compared to RA-SB
      (26.4% vs 13.9%; P < 0.001). CONCLUSION: Transperineal RA-TB and -SB showed
      similar clinically significant prostate cancer detection rates in primary and
      repeat biopsy settings. However, RA-TB offered a 50% reduction in biopsy cores.
      Omitting RA-SB is associated with a significant risk of missing clinically
      significant prostate cancer.

PMID- 29211935
TI  - A simple twist of phosphate: Immunological synapse formation and T cell receptor
      signaling outcome in regulatory T cells.
AB  - Signaling through the T cell receptor (TCR) regulates T cell homeostasis and
      effector functions. However, a full accounting of the TCR-coupled signaling
      networks and how their interplay determines specific functional outcomes remains
      elusive. Of particular interest are efforts over the last years to elucidate
      distinctive features of TCR signaling in regulatory T cells (Treg) that may
      account for some of their unique functional attributes as compared to
      conventional T (Tconv) cells. In this issue of the European Journal of
      Immunology, van Ham et al. [Eur. J. Immunol. 2017. 47: 2043-2058] employed
      differential phosphoproteomics to identify a set of 11 proteins mainly linked to
      cytoskeletal organization and molecular transport that discriminate between TCR
      signaling in the respective cell subset. They further linked these differences to
      cell subset-specific alterations in the spatio-temporal organization of signaling
      pathways at immune synapse (IS) in Treg versus T conv. These data support the
      idea that these proteins may act as a molecular "twist" element driving Treg cell
      specific responses by affecting cytoskeletal dynamics and IS formation. Taken
      together, these findings may facilitate the development of novel immunomodulatory
      agents that exploit differences in TCR signaling between Treg and Tconv cells.

PMID- 29211936
TI  - Avian Scavenging of Small-Sized Pig Carcasses in Central Florida: Utilizing GIS
      to Analyze Site Variables Affecting Skeletal Dispersal.
AB  - Scavengers can significantly alter a forensic scene and consume, modify,
      disarticulate, and disperse bodies on the ground surface. The research purpose
      was to examine vulture scavenging in central Florida, USA. Four small-sized pig
      (Sus scrofa) carcasses were left on the ground surface of two microenvironments
      (shaded and open) at a secure site with game cameras. Dispersal data were mapped
      and analyzed using geographical information systems spatial analysis digital
      mapping tools. The primary avian scavengers recorded included black vultures
      (Coragyps atratus) and turkey vultures (Cathartes aura), as well as bald eagles
      (Haliaeetus leucocephalus). Carcass dispersal patterns were impacted by foliage
      density (grass height and concentrations of bushes and trees) and proximity to
      the perimeter fence. While the majority of skeletal elements were dispersed
      within 6 m of the carcass deposition locations, dispersion occurred over a
      greater distance in the wooded microenvironment. Overall, vulture behaviors
      deleteriously destroyed and changed the context of the scene, with black vultures
      having the greatest impact.

PMID- 29211937
TI  - Reply.

PMID- 29211939
TI  - From the Editors.

PMID- 29211938
TI  - Polycystic liver disease: The interplay of genes causative for hepatic and renal
      cystogenesis.

PMID- 29211940
TI  - Liver fibrosis scores in the general population: Better risk indices are needed!

PMID- 29211942
TI  - Erratum.

PMID- 29211943
TI  - President's Letter December 2017.

PMID- 29211941
TI  - Impact of aberrant left hepatic artery ligation on the outcome of liver
      transplantation.
AB  - The preservation of a graft's aberrant left hepatic artery (LHA) during liver
      transplantation (LT) ensures optimal vascularization of the left liver but can
      also be considered a risk factor for hepatic artery thrombosis (HAT). In
      contrast, ligation of an aberrant LHA may lead to hepatic ischemia with the
      potential risk of graft dysfunction and biliary complications. The aim of this
      study was to prospectively analyze the impact on the surgical strategy for LT of
      5 tests performed to establish whether an aberrant LHA was an accessory or a
      replaced artery, thus leading to the design of a decisional algorithm. From
      August 2005 to December 2016, 395 whole LTs were performed in 376 patients. Five
      parameters were evaluated to determine whether an aberrant LHA was an accessory
      or a replaced artery. On the basis of our decision algorithm, an aberrant LHA was
      ligated during surgery when assessed as accessory and preserved when assessed as
      replaced. A total of 138 anatomical variants of hepatic arterial vascularization
      occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was
      63/395 (15.9%). The LHA was ligated in 33 (52.4%) patients and preserved in 30
      (47.6%) patients. After a mean follow-up period of 50.9 +/- 39.7 months, the
      incidence of HAT, primary nonfunction, early allograft dysfunction, biliary
      stricture or leaks, and overall survival was similar in the 2 groups. In
      conclusion, once shown to be an accessory, an LHA can be safely ligated without
      clinical consequences on the outcome of LT. Liver Transplantation 24 204-213 2018
      AASLD.

PMID- 29211944
TI  - Individuation for a DSM-5 disorder: Adult separation anxiety.

PMID- 29211946
TI  - A rare ANOS1 variant in siblings with Kallmann syndrome identified by whole exome
      sequencing.
AB  - Kallmann syndrome is a rare genetic condition causing congenital hypogonadotropic
      hypogonadism. It presents with delayed puberty, anosmia, and infertility. Here,
      we set out to identify a causative DNA variant for Kallmann syndrome in two
      affected brothers of Hispanic ancestry. The male siblings presented with a
      clinical diagnosis of Kallmann syndrome (anosmia, delayed puberty, azoospermia,
      and undetectable luteinizing hormone and follicle stimulating hormone levels).
      Genetic variations were investigated by whole exome sequencing. Potentially
      pathogenic variants were filtered and prioritized followed by validation by
      Sanger sequencing in the two brothers and their mother. A pathogenic variant was
      identified in the ANOS1 gene on the X chromosome: c.1267C>T; both brothers were
      hemizygous, and their mother was heterozygous for the variant. The variant is a
      single nucleotide change that introduces a stop codon in exon 9 (p.R423*), likely
      producing a truncated variant of the protein. This variant has only been reported
      twice in the literature, in the setting of finding genetic causes for other
      conditions. This result supports the clinical value of whole exome sequencing for
      identification of genetic pathogenic variants. Genetic diagnosis is the essential
      first step for genetic counseling, preimplantation diagnosis, and research for a
      potential treatment.

PMID- 29211945
TI  - Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the
      interaction between Nfu and the HSPA9/Hsc20 chaperone complex.
AB  - Iron-sulfur cluster biogenesis is a complex, but highly regulated process that
      involves de novo cluster formation from iron and sulfide ions on a scaffold
      protein, and subsequent delivery to final targets via a series of Fe-S cluster
      binding carrier proteins. The process of cluster release from the
      scaffold/carrier for transfer to the target proteins may be mediated by a
      dedicated Fe-S cluster chaperone system. In human cells, the chaperones include
      heat shock protein HSPA9 and the J-type chaperone Hsc20. While the role of
      chaperones has been somewhat clarified in yeast and bacterial systems, many
      questions remain over their functional roles in cluster delivery and interactions
      with a variety of human Fe-S cluster proteins. One such protein, Nfu, has
      recently been recognized as a potential interaction partner of the chaperone
      complex. Herein, we examined the ability of human Nfu to function as a carrier by
      interacting with the human chaperone complex. Human Nfu is shown to bind to both
      chaperone proteins with binding affinities similar to those observed for IscU
      binding to the homologous HSPA9 and Hsc20, while Nfu can also stimulate the
      ATPase activity of HSPA9. Additionally, the chaperone complex was able to promote
      Nfu function by enhancing the second-order rate constants for Fe-S cluster
      transfer to target proteins and providing directionality in cluster transfer from
      Nfu by eliminating promiscuous transfer reactions. Together, these data support a
      hypothesis in which Nfu can serve as an alternative carrier protein for chaperone
      mediated cluster release and delivery in Fe-S cluster biogenesis and trafficking.

PMID- 29211947
TI  - Tracking Ionic Rearrangements and Interpreting Dynamic Volumetric Changes in Two
      Dimensional Metal Carbide Supercapacitors: A Molecular Dynamics Simulation Study.
AB  - We present a molecular dynamics simulation study achieved on two-dimensional (2D)
      Ti3 C2 Tx MXenes in the ionic liquid 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([EMIM]+ [TFSI]- ) electrolyte. Our simulations
      reproduce the different patterns of volumetric change observed experimentally for
      both the negative and positive electrodes. The analysis of ionic fluxes and
      structure rearrangements in the 2D material provide an atomic scale insight into
      the charge and discharge processes in the layer pore and confirm the existence of
      two different charge-storage mechanisms at the negative and positive electrodes.
      The ionic number variation and the structure rearrangement contribute to the
      dynamic volumetric changes of both electrodes: negative electrode expansion and
      positive electrode contraction.

PMID- 29211948
TI  - Simultaneous determination of polysaccharides and 21 nucleosides and amino acids
      in different tissues of Salvia miltiorrhiza from different areas by UV-visible
      spectrophotometry and UHPLC with triple quadrupole MS/MS.
AB  - Salvia miltiorrhiza, a traditional Chinese medicine, is a widely used herbal
      medicine to treat cardiovascular and cerebrovascular diseases. In this study,
      ultraviolet (UV)-visible spectrophotometry and ultra-high performance liquid
      chromatography with triple quadrupole tandem mass spectrometry analytical methods
      were used for rapid quantification of polysaccharides and 21 nucleosides and
      amino acids in S. miltiorrhiza to determine 17 samples of different tissues from
      different areas. Based on the total contents, hierarchical clustering analysis
      and principal components analysis were performed to classify these samples. The
      established methods were validated with good linearity, precision, repeatability,
      stability, and recovery. Chemical analysis revealed a higher content of total
      analytes in the sample of inflorescence from Nanjing (34.17 mg/g), sample of root
      and rhizome from Shaanxi (34.13 mg/g) and sample of stem and leaf from Nanjing
      (31.14 mg/g), respectively, indicating that root and rhizome from Shaanxi and the
      aerial parts from Nanjing exhibited the highest quality due to their highest
      content. In addition, contents of nucleosides and amino acids in the aerial parts
      (14.67 mg/g) were much higher than that in roots and rhizomes (9.17 mg/g). This
      study suggested that UV-visible spectrophotometry and ultra-high performance
      liquid chromatography with triple quadrupole tandem mass spectrometry are
      effective techniques to analyze polysaccharides, nucleosides, and amino acids in
      plants, and they provided valuable information for the development and
      utilization value of the aerial parts of S. miltiorrhiza. This analysis would
      also provide useful information for the quality control of S. miltiorrhiza.

PMID- 29211949
TI  - Fluoride Uptake Profiles of Selected European Toothpastes into Hard Tissues and
      Plaque.
AB  - OBJECTIVES: To compare the fluoridating potential of selected European
      toothpastes using a combination of enamel, dentin, and plaque in vitromodels.
      METHODS: Four in vitromodels were included: 1) Enamel Fluoride (F) Uptake (EFU);
      2) Dentin F Uptake (DFU); 3) Enamel Solubility Reduction (ESR); and 4) Plaque F
      Uptake (PFU). A core set of marketed products was included in all studies, plus a
      standard toothpaste (1100 ppm F as NaF/silica) and placebo control (the PFU study
      did not include a placebo control). Test dentifrices: [A] Fluocaril(r) Bi-Fluore
      250 (1500 ppm F as NaF+1000 ppm F as SMFP); [B] LacerAnticaries (2500 ppm F as
      SMFP); [C] Elmex(r) Caries ProfessionalTM (1450 ppm F as SMFP+1.5% arginine); [D]
      Colgate(r) Triple Action (1450 ppm F as SMFP); [E] Placebo (0 ppm F); and [F]
      standard toothpaste (1100 ppm as NaF/silica). In all studies (EFU, DFU, ESR, and
      PFU), assessments were compared for each pair using the Tukey-Kramer HSD test (p
      < 0.05). RESULTS: In all studies of fluoride uptake, the Fluocaril dentifrice [A]
      provided the greatest numerical benefit, regardless of the substrate. Statistical
      groupings were EFU: A > F = B = C = D > E; DFU: A > F = B = C = D = E; PFU: A = B
      > F = C = D). In demineralization prevention, the Fluocaril dentifrice [A] also
      provided the greatest benefit (ESR: A = F = C = B = D > E). In all studies that
      included a placebo control, all of the F-containing dentifrices performed better
      than the placebo control. CONCLUSIONS: While these results demonstrate that all
      of the marketed products tested provide effective anticaries benefits, the
      Fluocaril Bi-Fluore 250 dentifrice consistently delivered unsurpassed
      performance. It delivered the highest level of F to plaque, provided greater
      measures of efficacy in both remineralization and inhibition of demineralization,
      and delivered substantial improvement in fluoridation of dentin, suggesting the
      potential for delivering both coronal and root caries benefits.

PMID- 29211950
TI  - Two Randomized Clinical Studies to Confirm Differential Plaque Removal by Sodium
      Bicarbonate Dentifrices in a Single Timed Brushing Model.
AB  - OBJECTIVES: This study evaluated and compared plaque removal efficacy of
      commercially available dentifrices containing sodium bicarbonate (NaHCO3) to
      those without NaHCO3 in a single timed brushing clinical study model. METHODS:
      Two randomized, examiner-blind, three-period, three-treatment, crossover studies
      were performed in adults with a mean Turesky modification of the Quigley-Hein
      Plaque Index (TPI) score of = 2.00. In Study 1, 60 subjects were randomized to
      commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm
      fluoride (F) as sodium fluoride (NaF); (ii) 45% NaHCO3 plus 1425 ppm F as NaF; or
      (iii) 0% NaHCO3 plus silica and 1450 ppm F as NaF. In Study 2, 55 subjects were
      randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus
      1425 ppm F as NaF; (ii) 0% NaHCO3 plus silica and 1400 ppm F as amine F/stannous
      F; or (iii) 0% NaHCO3 plus chlorhexidine/aluminum lactate and silica with 1360
      ppm F as aluminum F. In both studies, subjects brushed their teeth for one timed
      minute under supervised conditions. Plaque was assessed pre- and post-brushing
      according to a six-site modification of the TPI. Mean TPI score was analyzed
      using an analysis of covariance model with treatment and study period as fixed
      effects, subject as a random variable, and pre-brushing score as a covariate.
      RESULTS: In both studies, mean TPI score decreased in all groups post-brushing
      compared with pre-brushing. In Study 1, statistically significant improvements in
      mean TPI score were reported with the 67% and 45% NaHCO3 dentifrices compared
      with the 0% NaHCO3 dentifrice (p = 0.0003 and p = 0.0005, respectively). In Study
      2, improvements in mean TPI score were statistically significantly greater with
      the 67% NaHCO3 dentifrice compared with both 0% NaHCO3 dentifrices (p < 0.0001
      for both comparisons). All dentifrices were generally well tolerated.
      CONCLUSIONS: A single timed brushing with commercially available dentifrices
      containing 67% or 45% NaHCO3 exerted a significantly greater effect on plaque
      removal than commercially available dentifrices without NaHCO3.

PMID- 29211951
TI  - A Double-Blinded, Randomized Study Evaluating the In Vivo Effects of a Novel
      Dental Gel on Enamel Surface Microstructure and Microhardness.
AB  - OBJECTIVES: The objective of this study was to evaluate the in vivo effects of a
      2.6% edathamil gel (Livionex(r) Dental Gel) on surface microhardness and
      microstructure in 180 pre-eroded enamel chips. METHODS: This was a double-blind,
      randomized study. Two enamel chips each were cut from 90 healthy sterilized
      extracted teeth. One chip from each pair underwent microhardness testing and
      scanning electron microscopy (SEM) to establish baselines. The remaining 90
      samples were demineralized, and then mounted onto intra-oral retainers worn by
      nine subjects, with five chips mounted on each retainer for each of the two study
      arms. In one two-week study arm subjects brushed with the control toothpaste; in
      the other they used the test gel. Study arms were separated by a two-week
      washout. Sequence of toothpaste use was randomized. At the end of each study arm,
      samples underwent microhardness measurements (Knoop) and SEM visualization.
      RESULTS: After intraoral wear, enamel chips recovered fully from
      demineralization, with no significant difference in microhardness between the two
      treatments (p > 0.05). In SEM images, enamel surfaces at study's end also
      appeared comparable in the two groups. CONCLUSIONS: Pre-eroded enamel chips
      remineralized intra-orally to a similar level after using a control or a test
      toothpaste containing 2.6% edathamil.

PMID- 29211952
TI  - A Profilometry-Based Dentifrice Abrasion Method for V8 Brushing Machines Part
      III: Multi-Laboratory Validation Testing of RDA-PE.
AB  - OBJECTIVES: We have previously reported on progress toward the refinement of
      profilometry-based abrasivity testing of dentifrices using a V8 brushing machine
      and tactile or optical measurement of dentin wear. The general application of
      this technique may be advanced by demonstration of successful inter-laboratory
      confirmation of the method. The objective of this study was to explore the
      capability of different laboratories in the assessment of dentifrice abrasivity
      using a profilometry-based evaluation technique developed in our Mason
      laboratories. In addition, we wanted to assess the interchangeability of human
      and bovine specimens. METHODS: Participating laboratories were instructed in
      methods associated with Radioactive Dentin Abrasivity-Profilometry Equivalent
      (RDA-PE) evaluation, including site visits to discuss critical elements of
      specimen preparation, masking, profilometry scanning, and procedures.
      Laboratories were likewise instructed on the requirement for demonstration of
      proportional linearity as a key condition for validation of the technique.
      Laboratories were provided with four test dentifrices, blinded for testing, with
      a broad range of abrasivity. In each laboratory, a calibration curve was
      developed for varying V8 brushing strokes (0, 4,000, and 10,000 strokes) with the
      ISO abrasive standard. Proportional linearity was determined as the ratio of
      standard abrasion mean depths created with 4,000 and 10,000 strokes (2.5 fold
      differences). Criteria for successful calibration within the method (established
      in our Mason laboratory) was set at proportional linearity = 2.5 +/- 0.3. RDA-PE
      was compared to Radiotracer RDA for the four test dentifrices, with the latter
      obtained by averages from three independent Radiotracer RDA sites. Individual
      laboratories and their results were compared by 1) proportional linearity and 2)
      acquired RDA-PE values for test pastes. RESULTS: Five sites participated in the
      study. One site did not pass proportional linearity objectives. Data for this
      site are not reported at the request of the researchers. Three of the remaining
      four sites reported herein tested human dentin and all three met proportional
      linearity objectives for human dentin. Three of four sites participated in
      testing bovine dentin and all three met the proportional linearity objectives for
      bovine dentin. RDA-PE values for test dentifrices were similar between sites. All
      four sites that met proportional linearity requirement successfully identified
      the dentifrice formulated above the industry standard 250 RDA (as RDA-PE). The
      profilometry method showed at least as good reproducibility and differentiation
      as Radiotracer assessments. It was demonstrated that human and bovine specimens
      could be used interchangeably. CONCLUSIONS: The standardized RDA-PE method was
      reproduced in multiple laboratories in this inter-laboratory study. Evidence
      supports that this method is a suitable technique for ISO method 11609 Annex B.

PMID- 29211953
TI  - The Effect of a Toothbrush Handle Design in Combating Microbial Contamination.
AB  - OBJECTIVES: This study aims to assess the difference in microbial contamination
      of a toothbrush with a smooth handle versus a toothbrush with a grooved handle
      design. METHODS: Twenty-six volunteers were randomized into two groups. The first
      group used a smooth handle toothbrush for two months, followed by a grooved
      handle toothbrush for two months. The second group had the order reversed.
      Following the two-month use, the toothbrushes were submitted for microbial
      analysis. Effect size, as well as Wilcoxon signed-rank test were used to
      calculate the differences between total colony count, bacterial DNA, and
      endotoxin levels from the two toothbrush handle types. RESULTS: There was no
      significant difference in colony count between the smooth (mean 580 CFU/mL, SD
      1,684 CFU/mL) and grooved (mean 19,059 CFU/mL, SD 80,972 CFU/mL) handles (p =
      0.12). Total DNA count was significantly less (p = 0.01) on the smooth handle
      (mean 68,038 RFU/mL, SD 81,659) compared to the grooved handle (mean 209,312
      RFU/mL, SD 257,169 RFU/mL). Endotoxin levels were significantly less (p = 0.01)
      on the smooth handle (mean 0.16 EU/mL, SD 0.30 EU/mL) compared to the grooved
      handle (mean 0.43 EU/mL, SD 0.49 EU/mL). CONCLUSIONS: The smooth handle
      toothbrush had significantly less bacterial contamination compared to the grooved
      handle toothbrush, as measured by total DNA count and endotoxin levels.

PMID- 29211954
TI  - siRNA Delivery with Chitosan: Influence of Chitosan Molecular Weight, Degree of
      Deacetylation, and Amine to Phosphate Ratio on in Vitro Silencing Efficiency,
      Hemocompatibility, Biodistribution, and in Vivo Efficacy.
AB  - Chitosan (CS) shows in vitro and in vivo efficacy for siRNA delivery but with
      contradictory findings for incompletely characterized systems. For understanding
      which parameters produce effective delivery, a library of precisely characterized
      chitosans was produced at different degrees of deacetylation (DDAs) and average
      molecular weights (Mn). Encapsulation and transfection efficiencies were
      characterized in vitro. Formulations were selected to examine the influence of Mn
      and N:P ratio on nanoparticle uptake, metabolic activity, genotoxicity, and in
      vitro transfection. Hemocompatibility and in vivo biodistribution were then
      investigated for different Mn, N:P ratios, and doses. Nanoparticle uptake and
      gene silencing correlated with increased surface charge, which was obtained at
      high DDA and high Mn. A minimum polymer length of ~60-70 monomers (~10 kDa) was
      required for stability and knockdown. In vitro knockdown was equivalent to lipid
      control with no metabolic or genotoxicity. An inhibitory effect of serum on
      biological performance was dependent on DDA, Mn, and N:P. In vivo biodistribution
      in mice show accumulation of nanoparticles in kidney with 40-50% functional
      knockdown.

PMID- 29211956
TI  - Toxicity Assessment of Iron Oxide Nanoparticles Based on Cellular Magnetic
      Loading Using Magnetophoretic Sorting in a Trapezoidal Microchannel.
AB  - To accurately assess potential nanotoxicity on the basis of cellular iron
      content, the precise separation of cells into subpopulations according to their
      magnetic nanoparticle loading is of crucial importance. In this study, we
      developed a microfluidic magnetophoresis device consisting of a trapezoidal
      channel containing five side outlet branches and a narrow rectangular channel
      with three outlet branches. This unique structure enabled the sequential
      separation of cells loaded with tiny amounts of iron oxide and cells heavily
      labeled with iron oxide, in a single device. As a proof of concept, we attempted
      the sequential separation of Raw 264.7 cells with a large heterogeneity in uptake
      capabilities (1-50 pg of iron per cell). Consequently, we were able to
      differentiate the bulk cell population into seven subpopulations according to
      their mean iron oxide loading. We also evaluated potential nanotoxicity effects
      using the production of excess reactive oxygen species (ROS) and the inhibition
      of proliferation on the separated subpopulations, and we found that 46.6% of
      cells loaded with iron above the threshold value (16.4 pg) had higher ROS levels
      than the control group. Cells loaded with more than 3.7 pg of iron exhibited
      transiently inhibited cell-cycle progression. In particular, cells loaded with
      more than 35.4 pg of iron exerted a significant effect on cell proliferation. The
      proposed system could be useful in the investigation of nanotoxicity effects of
      iron oxide nanoparticle-induced cells, based on their iron oxide nanoparticle
      loading.

PMID- 29211955
TI  - Biochemical and Spectroscopic Observation of Mn(II) Sequestration from Bacterial
      Mn(II) Transport Machinery by Calprotectin.
AB  - Human calprotectin (CP, S100A8/S100A9 oligomer) is a metal-sequestering host
      defense protein that prevents bacterial acquisition of Mn(II). In this work, we
      investigate Mn(II) competition between CP and two solute-binding proteins that
      Staphylococcus aureus and Streptococcus pneumoniae, Gram-positive bacterial
      pathogens of significant clinical concern, use to obtain Mn(II) when infecting a
      host. Biochemical and electron paramagnetic resonance (EPR) spectroscopic
      analyses demonstrate that CP outcompetes staphylococcal MntC and streptococcal
      PsaA for Mn(II). This behavior requires the presence of excess Ca(II) ions, which
      enhance the Mn(II) affinity of CP. This report presents new spectroscopic
      evaluation of two Mn(II) proteins important for bacterial pathogenesis, direct
      observation of Mn(II) sequestration from bacterial Mn(II) acquisition proteins by
      CP, and molecular insight into the extracellular battle for metal nutrients that
      occurs during infection.

PMID- 29211957
TI  - Binding Mechanisms of Electron Transport Proteins with Cyanobacterial Photosystem
      I: An Integrated Computational and Experimental Model.
AB  - The stromal domain (PsaC, D, and E) of photosystem I (PSI) in cyanobacteria
      accepts electrons from PsaA and PsaB of photosystem I (PSI). These electrons are
      then used in the reduction of transiently bound ferredoxin (Fd) or flavodoxin.
      Experimental X-ray and NMR structures are known for all of these protein partners
      separately, yet to date, there is no known experimental structure of the PSI/Fd
      complexes in the published literature. Computational models of Fd docked with the
      stromal domain of cyanobacterial PSI were assembled here starting from X-ray and
      NMR structures of PSI and Fd. Predicted models of specific regions of protein
      protein interactions were built on the basis of energetic frustration, residue
      conservation and evolutionary importance, as well as from experimental site
      directed mutagenesis and cross-linking studies. Microsecond time-scale molecular
      dynamics simulations of the PSI/Fd complexes suggest, rather than a single
      complex structure, the possible existence of multiple transient complexes of Fd
      bound to PSI.

PMID- 29211958
TI  - Core-Shell-Yarn-Based Triboelectric Nanogenerator Textiles as Power Cloths.
AB  - Although textile-based triboelectric nanogenerators (TENGs) are highly promising
      because they scavenge energy from their working environment to sustainably power
      wearable/mobile electronics, the challenge of simultaneously possessing the
      qualities of cloth remains. In this work, we propose a strategy for TENG textiles
      as power cloths in which core-shell yarns with core conductive fibers as the
      electrode and artificial polymer fibers or natural fibrous materials tightly
      twined around core conductive fibers are applied as the building blocks. The
      resulting TENG textiles are comfortable, flexible, and fashionable, and their
      production processes are compatible with industrial, large-scale textile
      manufacturing. More importantly, the comfortable TENG textiles demonstrate
      excellent washability and tailorability and can be fully applied in further
      garment processing. TENG textiles worn under the arm or foot have also been
      demonstrated to scavenge various types of energy from human motion, such as
      patting, walking, and running. All of these merits of proposed TENG textiles for
      clothing uses suggest their great potentials for viable applications in wearable
      electronics or smart textiles in the near future.

PMID- 29211959
TI  - Chemical Pressure Maps of Molecules and Materials: Merging the Visual and
      Physical in Bonding Analysis.
AB  - The characterization of bonding interactions in molecules and materials is one of
      the major applications of quantum mechanical calculations. Numerous schemes have
      been devised to identify and visualize chemical bonds, including the electron
      localization function, quantum theory of atoms in molecules, and natural bond
      orbital analysis, whereas the energetics of bond formation are generally analyzed
      in qualitative terms through various forms of energy partitioning schemes. In
      this Article, we illustrate how the chemical pressure (CP) approach recently
      developed for analyzing atomic size effects in solid state compounds provides a
      basis for merging these two approaches, in which bonds are revealed through the
      forces of attraction and repulsion acting between the atoms. Using a series of
      model systems that include simple molecules (H2, CO2, and S8), extended
      structures (graphene and diamond), and systems exhibiting intermolecular
      interactions (ice and graphite), as well as simple representatives of metallic
      and ionic bonding (Na and NaH, respectively), we show how CP maps can
      differentiate a range of bonding phenomena. The approach also allows for the
      partitioning of the potential and kinetic contributions to the interatomic
      interactions, yielding schemes that capture the physical model for the chemical
      bond offered by Ruedenberg and co-workers.

PMID- 29211960
TI  - Exchange Coupling Interactions from the Density Matrix Renormalization Group and
      N-Electron Valence Perturbation Theory: Application to a Biomimetic Mixed-Valence
      Manganese Complex.
AB  - The accurate description of magnetic level energetics in oligonuclear exchange
      coupled transition-metal complexes remains a formidable challenge for quantum
      chemistry. The density matrix renormalization group (DMRG) brings such systems
      for the first time easily within reach of multireference wave function methods by
      enabling the use of unprecedentedly large active spaces. But does this guarantee
      systematic improvement in predictive ability and, if so, under which conditions?
      We identify operational parameters in the use of DMRG using as a test system an
      experimentally characterized mixed-valence bis-MU-oxo/MU-acetato Mn(III,IV)
      dimer, a model for the oxygen-evolving complex of photosystem II. A complete
      active space of all metal 3d and bridge 2p orbitals proved to be the smallest
      meaningful starting point; this is readily accessible with DMRG and greatly
      improves on the unrealistic metal-only configuration interaction or complete
      active space self-consistent field (CASSCF) values. Orbital optimization is
      critical for stabilizing the antiferromagnetic state, while a state-averaged
      approach over all spin states involved is required to avoid artificial deviations
      from isotropic behavior that are associated with state-specific calculations.
      Selective inclusion of localized orbital subspaces enables probing the relative
      contributions of different ligands and distinct superexchange pathways. Overall,
      however, full-valence DMRG-CASSCF calculations fall short of providing a
      quantitative description of the exchange coupling owing to insufficient recovery
      of dynamic correlation. Quantitatively accurate results can be achieved through a
      DMRG implementation of second order N-electron valence perturbation theory
      (NEVPT2) in conjunction with a full-valence metal and ligand active space.
      Perspectives for future applications of DMRG-CASSCF/NEVPT2 to exchange coupling
      in oligonuclear clusters are discussed.

PMID- 29211961
TI  - Scalable Electron Correlation Methods. 5. Parallel Perturbative Triples
      Correction for Explicitly Correlated Local Coupled Cluster with Pair Natural
      Orbitals.
AB  - A well-parallelized perturbative triples correction implementation for the pair
      natural orbital based coupled cluster method PNO-LCCSD(T)-F12 is presented. A
      composite approach is adopted in addressing the coupling due to off-diagonal Fock
      matrix elements, in which the local triples amplitudes are iteratively solved
      using small domains of triples natural orbitals, and a semicanonical (T0) domain
      correction with larger domains is applied to reduce the domain errors. This
      treatment adds only about 20% to the computational cost of (T0) calculations with
      large domains, and the errors due to the use of small domains in the iterations
      are very small. In addition, a two-step triple list selection method is applied:
      First, an initial triple list is generated using LCCSD-F12 pair energy criteria,
      and the (T0) triples energies are computed using small domains. Second, this list
      is reduced by neglecting triples with small energy contributions, and the final
      calculation with large domains is only carried out for the reduced list. The cost
      of the (T) calculation scales asymptotically linear with the molecular size and
      shows excellent parallelization efficiency up to hundreds of CPU cores. The
      convergence of the (T) contribution to the relative energies of large molecular
      systems is carefully tested, and for most of the cases the results obtained with
      our default thresholds agree within ~0.5 kcal mol-1 with those computed with very
      tight thresholds. For all tested molecular systems where canonical calculations
      are still feasible, the PNO-LCCSD(T)-F12 relative energies also agree within 0.5
      kcal mol-1 with the canonical CCSD(T)-F12 results using the same F12 treatment.
      The (T) calculation generally takes 3-5 times the cost of the preceding PNO-LCCSD
      F12 calculation, primarily due to the large number of triples required in
      obtaining accurate relative energies. We find that for large molecular systems
      the triple selection criteria used in previous local triples methods are
      insufficient, and a much larger number of triples are required than it was
      assumed so far. Still, using a commodity computer cluster, the PNO-LCCSD(T)-F12
      calculation of molecules with ~100 atoms using augmented triple-zeta basis sets
      can be carried out in a few hours of elapsed time.

PMID- 29211962
TI  - Highly Sensitive Detection of Salmonella typhimurium Using a Colorimetric Paper
      Based Analytical Device Coupled with Immunomagnetic Separation.
AB  - Salmonella causes over a million foodborne illnesses per year in the United
      States resulting in more hospitalizations and deaths than any other foodborne
      bacterial pathogen. To help prevent outbreaks, a rapid, portable, sensitive, and
      reliable method for onsite detection of bacteria that can be used in different
      sample matrices would be beneficial. Herein, we present a colorimetric paper
      based analytical device (PAD) combined with immunomagnetic separation (IMS) for
      detecting Salmonella typhimurium. IMS anti-Salmonella coated magnetic beads were
      applied to capture and separate bacteria from the sample matrix and
      preconcentrate it into small volumes before testing on paper. To directly detect
      S. typhimurium after IMS, a sandwich immunoassay was implemented into the
      procedure with beta-galactosidase (beta-gal) as the detection enzyme. Using the
      antibody/enzyme complex, we performed a colorimetric assay with chlorophenol red
      beta-d-galactopyranoside (CPRG) for bacteria quantification. The method was
      confirmed to be highly specific to S. typhimurium without interference from other
      pathogenic bacteria like Escherichia coli. Using this system, the limit of
      detection of S. typhimurium was found to be 102 CFU mL-1 in culturing solution
      without any pre-enrichment. In addition, distance-based detection where the
      concentration is read as the length of colored band formed on the reaction was
      also demonstrated. This assay had a detection limit of 102 CFU mL-1 for S.
      typhimurium, providing an instrument-free quantitative analysis alternative to
      spot tests, which require image analysis. Finally, the proposed platform was
      applied for detection of S. typhimurium in inoculated Starling bird fecal samples
      and whole milk with detection limits of 105 CFU g-1 and 103 CFU mL-1,
      respectively, and this is the first published paper-based detection method for S.
      typhimurium in bird feces and whole milk.

PMID- 29211963
TI  - Dynamic Organization of Ligand-Grafted Nanoparticles during Adsorption and
      Surface Compression at Fluid-Fluid Interfaces.
AB  - Monolayers of ligand-grafted nanoparticles at fluid interfaces exhibit a complex
      response to deformation due to an interplay of particle rearrangements within the
      monolayer, and molecular rearrangements of the ligand brush on the surface of the
      particles. We use grazing-incidence small-angle X-ray scattering (GISAXS)
      combined with pendant drop tensiometry to probe in situ the dynamic organization
      of ligand-grafted nanoparticles upon adsorption at a fluid-fluid interface, and
      during monolayer compression. Through the simultaneous measurements of
      interparticle distance, obtained from GISAXS, and of surface pressure, obtained
      from pendant drop tensiometry, we link the interfacial stress to the monolayer
      microstructure. The results indicate that, during adsorption, the nanoparticles
      form rafts that grow while the interparticle distance remains constant. For small
      amplitude, slow compression of the monolayer, the evolution of the interparticle
      distance bears a signature of ligand rearrangements leading to a local decrease
      in thickness of the ligand brush. For large-amplitude compression, the surface
      pressure is found to be strongly dependent on the rate of compression. Two
      dimensional Brownian dynamics simulations show that the rate-dependent features
      are not due to jamming of the monolayer, and suggest that they may be due to out
      of-plane reorganization of the particles (for instance expulsion or buckling).
      The corresponding GISAXS patterns are also consistent with out-of-plane
      reorganization of the nanoparticles.

PMID- 29211964
TI  - Metabolic Costs of Exposure to Wastewater Effluent Lead to Compensatory
      Adjustments in Respiratory Physiology in Bluegill Sunfish.
AB  - Municipal wastewater effluent is a major source of aquatic pollution and has
      potential to impact cellular energy metabolism. However, it is poorly understood
      whether wastewater exposure impacts whole-animal metabolism and whether this can
      be accommodated with adjustments in respiratory physiology. We caged bluegill
      sunfish (Lepomis macrochirus) for 21 days at two sites downstream (either 50 or
      830 m) from a wastewater treatment plant (WWTP). Survival was reduced in fish
      caged at both downstream sites compared to an uncontaminated reference site.
      Standard rates of O2 consumption increased in fish at contaminated sites,
      reflecting a metabolic cost of wastewater exposure. Several physiological
      adjustments accompanied this metabolic cost, including an expansion of the gill
      surface area available for gas exchange (reduced interlamellar cell mass), a
      decreased blood-O2 affinity (which likely facilitates O2 unloading at respiring
      tissues), increased respiratory capacities for oxidative phosphorylation in
      isolated liver mitochondria (supported by increased succinate dehydrogenase, but
      not citrate synthase, activity), and decreased mitochondrial emission of reactive
      oxygen species (ROS). We conclude that exposure to wastewater effluent invokes a
      metabolic cost that leads to compensatory respiratory improvements in O2 uptake,
      delivery, and utilization.

PMID- 29211965
TI  - Early Detection of Biofouling on Water Purification Membranes by Ambient
      Ionization Mass Spectrometry Imaging.
AB  - By direct analysis of water purification membranes using ambient ionization mass
      spectrometry, an attempt has been made to understand the molecular signatures of
      bacterial fouling. Membrane based purification methods are used extensively in
      water treatment, and a major challenge for them is biofouling. The buildup of
      microbes and their extracellular polymeric matrix clog the purification membranes
      and reduce their efficiency. To understand the early stages of bacterial fouling
      on water purification membranes, we have used desorption electrospray ionization
      mass spectrometry (DESI MS), where ion formation occurs in ambient conditions and
      the ionization event is surface sensitive. Biosurfactants at the air-water
      interface generated by microorganisms as a result of quorum sensing, influence
      the water-membrane interface and are important for the bacterial attachment. We
      show that these biosurfactants produced by bacteria can be indicator molecular
      species signifying initiation of biofilms on membrane surfaces, demonstrated by
      specific DESI MS signatures. In Pseudomonas aeruginosa, one of the best studied
      models for biofilm formation, this process is mediated by rhamnolipids
      forewarning bacterial fouling. Species dependent variation of such molecules can
      be used for the precise identification of the microorganisms, as revealed by
      studies on P. aeroginosa (ATCC 25619). The production of biosurfactants is
      tightly regulated at the transcriptional level by the quorum-sensing (QS)
      response. Thus, secretion of these extracellular molecules across the membrane
      surface allows rapid screening of the biofilm community. We show that, the
      ambient ionization mass spectrometry can detect certain toxic heavy metals
      present in water, using surfactant-metal complexes as analytes. We believe that
      such studies conducted on membranes in various input water streams will help
      design suitable membrane processes specific to the input streams.

PMID- 29211966
TI  - Analytic Gradients for Complete Active Space Pair-Density Functional Theory.
AB  - Analytic gradient routines are a desirable feature for quantum mechanical
      methods, allowing for efficient determination of equilibrium and transition state
      structures and several other molecular properties. In this work, we present
      analytical gradients for multiconfiguration pair-density functional theory (MC
      PDFT) when used with a state-specific complete active space self-consistent field
      reference wave function. Our approach constructs a Lagrangian that is variational
      in all wave function parameters. We find that MC-PDFT locates equilibrium
      geometries for several small- to medium-sized organic molecules that are similar
      to those located by complete active space second-order perturbation theory but
      that are obtained with decreased computational cost.

PMID- 29211967
TI  - Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children
      with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: To determine the efficacy and safety of amphetamine extended-release
      oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity
      disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group
      study. METHODS: Boys and girls aged 6 to 12 years diagnosed with ADHD were
      enrolled. During a 5-week, open-label, dose-optimization phase, patients began
      treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal
      dose (maximum 20 mg/day) was reached. During the double-blind phase, patients
      were randomized to receive treatment with either their optimized dose (10-20
      mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory
      classroom setting on the final day of double-blind treatment using the Swanson,
      Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product
      Measure of Performance (PERMP) test. Safety was assessed measuring adverse events
      (AEs) and vital signs. RESULTS: The study was completed by 99 patients. The
      primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours
      postdose) and secondary endpoints (change from predose SKAMP-Combined scores at
      1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly
      improved with AMPH EROS treatment versus placebo at all time points. Onset of
      treatment effect was present by 1 hour postdosing, the first time point measured,
      and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the
      SKAMP-Combined score data. AEs (>5%) reported during dose optimization were
      decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings,
      and headache. CONCLUSION: AMPH EROS was effective in reducing symptoms of ADHD
      and had a rapid onset and extended duration of effect. Reported AEs were
      consistent with those of other extended-release amphetamine products.

PMID- 29211968
TI  - Men and Women Differ in the Biochemical Composition of Platelet-Rich Plasma.
AB  - BACKGROUND: Autologous platelet-rich plasma (PRP) is widely used for a variety of
      clinical applications. However, clinical outcome studies have not consistently
      shown positive effects. The composition of PRP differs based on many factors. An
      improved understanding of factors influencing the composition of PRP is important
      for the optimization of PRP use. HYPOTHESIS: Age and sex influence the PRP
      composition in healthy patients. STUDY DESIGN: Controlled laboratory study.
      METHODS: Blood from 39 healthy patients was collected at a standardized time and
      processed into leukocyte-poor PRP within 1 hour of collection using the same
      laboratory centrifuge protocol and frozen for later analysis. Eleven female and
      10 male patients were "young" (aged 18-30 years), while 8 male and 10 female
      patients were "older" (aged 45-60 years). Thawed PRP samples were assessed for
      cytokine and growth factor levels using a multiplex assay and enzyme-linked
      immunosorbent assay. The platelet count and high-sensitivity C-reactive protein
      levels were measured. Two-way analysis of variance determined age- and sex-based
      differences. RESULTS: Platelet and high-sensitivity C-reactive protein
      concentrations were similar in PRP between the groups ( P = .234). Male patients
      had higher cytokine and growth factor levels in PRP compared with female patients
      for inflammatory cytokines such as interleukin-1 beta (IL-1beta) (9.83 vs 7.71
      pg/mL, respectively; P = .008) and tumor necrosis factor-alpha (TNF-alpha) (131.6
      vs 110.5 pg/mL, respectively; P = .048); the anti-inflammatory IL-1 receptor
      antagonist protein (IRAP) (298.0 vs 218.0 pg/mL, respectively; P < .001); and
      growth factors such as fibroblast growth factor-basic (FGF-basic) (237.9 vs 194.0
      pg/mL, respectively; P = .01), platelet-derived growth factor (PDGF-BB) (3296.2
      vs 2579.3 pg/mL, respectively; P = .087), and transforming growth factor-beta 1
      (TGF-beta1) (118.8 vs 92.8 ng/mL, respectively; P = .002). Age- but not sex
      related differences were observed for insulin-like growth factor-1 (IGF-1) ( P <
      .001). Age and sex interaction terms were not significant. While mean differences
      were significant, there was also substantial intragroup variability. CONCLUSION:
      This study in healthy patients shows differences in the composition of PRP
      between men and women, with sex being a greater factor than age. There was also
      proteomic variability within the groups. These data support a personalized
      approach to PRP treatment and highlight the need for a greater understanding of
      the relationships between proteomic factors in PRP and clinical outcomes.
      CLINICAL RELEVANCE: Variability in the proteomic profile of PRP may affect tissue
      and clinical responses to treatment. These data suggest that clinical studies
      should account for the composition of PRP used.

PMID- 29211969
TI  - Use of Platelet-Rich Plasma Immediately After an Injury Did Not Improve Ligament
      Healing, and Increasing Platelet Concentrations Was Detrimental in an In Vivo
      Animal Model.
AB  - BACKGROUND: Limited information in basic science and clinical trials exists to
      determine if ligament healing may be accelerated with the use of biological
      adjuvants, such as platelet-rich plasma (PRP). However, there has been widespread
      acceptance of PRP for use in clinical practice, despite an inadequate
      understanding of its biological mechanism of action. PURPOSE: To determine
      whether a single dose of PRP could accelerate ligament healing and
      correspondingly improve histological characteristics and biomechanical properties
      when injected immediately postoperatively into the injured medial collateral
      ligament (MCL) of New Zealand White rabbits. STUDY DESIGN: Controlled laboratory
      study. METHODS: Eighty skeletally mature New Zealand White rabbits (160 knees)
      were used. The MCL was torn midbody to simulate a grade 3 tear. After an acute
      injury of the MCL, the administration of autologous PRP at 3 different platelet
      concentrations (0 million/uL, platelet-poor plasma [PPP]; 0.6 million/uL, 2 times
      the baseline [2* PRP]; and 1.2 million/uL, 4 times the baseline [4* PRP]) was
      performed and compared with a saline injection control in the contralateral knee.
      Histological analysis and a biomechanical endpoint characterization were utilized
      to assess ligamentous healing and compare it to a sham surgery group. RESULTS:
      The PPP ( P = .001) and 4* PRP ( P = .002) groups had a significantly lower
      collagen subscore than the sham surgery group. No other differences were observed
      among the treatment groups, including the vascularity subscore and overall
      ligament tissue maturity index score. Compared with saline-injected contralateral
      knees, the maximum load for PPP and 2* PRP was not significantly different ( P =
      .788 and .325, respectively). The maximum load and stiffness for knees treated
      with 4* PRP were significantly less than for the saline-treated contralateral
      knees ( P = .006 and .001, respectively). CONCLUSION: One single dose of PPP or
      2* PRP at the time of injury did not improve ligament healing. In addition, 4*
      PRP negatively affected ligament strength and histological characteristics at 6
      weeks after the injury. CLINICAL RELEVANCE: The current practice of treating knee
      ligament injuries with PRP may not improve healing at low doses of PRP. The
      decreased mechanical properties and histological appearance of the torn MCL
      suggest that high doses of PRP decrease the quality of repair tissue. Further in
      vivo studies are necessary to determine the dosing and timing of PRP
      administration after a ligament injury before the widespread use of PRP to treat
      ligament injuries is recommended.

PMID- 29211970
TI  - Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage
      Grafts Produced From Auricular Chondrocytes.
AB  - BACKGROUND: Insufficient cell numbers still present a challenge for articular
      cartilage repair. Converting heterotopic auricular chondrocytes by extracellular
      matrix may be the solution. HYPOTHESIS: Specific extracellular matrix may convert
      the phenotype of auricular chondrocytes toward articular cartilage for repair.
      STUDY DESIGN: Controlled laboratory study. METHODS: For in vitro study, rabbit
      auricular chondrocytes were cultured in monolayer for several passages until
      reaching status of dedifferentiation. Later, they were transferred to
      chondrogenic type II collagen (Col II)-coated plates for further cell conversion.
      Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular
      chondrogenic gene, and protein expression, were evaluated after 14-day
      cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II
      hydrogel-associated auricular chondrocytes, and their histological and
      biomechanical properties were analyzed. For in vivo study, focal osteochondral
      defects were created in the rabbit knee joints, and auricular Col II constructs
      were implanted for repair. RESULTS: The auricular chondrocytes converted by a 2
      step protocol expressed specific profiles of chondrogenic molecules associated
      with articular chondrocytes. The histological and biomechanical features of
      converted auricular chondrocytes became similar to those of articular
      chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo
      animal model of osteochondral defects, the treated group (auricular Col II)
      showed better cartilage repair than did the control groups (sham, auricular
      cells, and Col II). Histological analyses revealed that cartilage repair was
      achieved in the treated groups with abundant type II collagen and
      glycosaminoglycans syntheses rather than elastin expression. CONCLUSION: The
      study confirmed the feasibility of applying heterotopic chondrocytes for
      cartilage repair via extracellular matrix-induced cell conversion. CLINICAL
      RELEVANCE: This study proposes a feasible methodology to convert heterotopic
      auricular chondrocytes for articular cartilage repair, which may serve as
      potential alternative sources for cartilage repair.

PMID- 29211971
TI  - Sold as Heroin: Perceptions and Use of an Evolving Drug in Baltimore, MD.
AB  - Since 2001, heroin-related overdose deaths in the United States have risen six
      fold, a rise unaccounted for by the expanding user population. Has heroin become
      a more dangerous drug? Reports of fentanyl and its analogs, often concealed in or
      sold as heroin, have also increased sharply. This article investigates heroin
      injectors' perceptions and experiences of changes in the heroin supply in the
      East Coast city of Baltimore, Maryland, currently facing an epidemic in heroin-
      and fentanyl-related overdose deaths. Unusually, Baltimore's heroin market is
      divided between two types: "Raw," believed to be Colombian in origin and
      relatively pure, and the more adulterated "Scramble" (raw heroin traditionally
      blended with quinine and lactose). Users reported that Scramble heroin, while
      gaining market share, has become a highly unstable product, varying dramatically
      in appearance, intensity of onset, duration of action, and effect. Some
      considered that Scramble was no longer "heroin," but was heavily adulterated or
      even replaced, mentioning fentanyl, benzodiazepines, and crushed opioid pills as
      additives. There was intense awareness of overdose as a present danger in users'
      lives, which they linked to the recent adulteration of the heroin supply.
      Responses to this perceived adulteration varied, including information gathering,
      attraction, avoidance, taking precautions, and acceptance.

PMID- 29211972
TI  - Reduction of cadmium uptake in rice endophytically colonized with the cadmium
      tolerant bacterium Cupriavidus taiwanensis KKU2500-3.
AB  - The effects of the cadmium (Cd)-tolerant bacterium Cupriavidus taiwanensis
      KKU2500-3 on the growth, yield, and Cd concentration in rice grains were
      investigated in the rice variety Phitsanulok 2 (PL2), which was cultivated in a
      hydroponic greenhouse. The numbers of Cd-tolerant bacteria isolated from the
      roots and shoots of plants under the RB (rice with bacteria) and RBC (rice with
      bacteria and Cd) treatments ranged from 2.60 to 9.03 and from 3.99 to 9.60 log
      cfu.g-1 of PL2, respectively. This KKU2500-3 strain was successfully colonized in
      rice, indicating that it was not only nontoxic to the plants but also became
      distributed and reproduced throughout the plants. Scanning electron microscopy
      analysis revealed attachment of the bacterium to the root surface, whereas the
      internally colonized bacteria were located in the vascular tissue, cell wall, and
      intercellular space. Although the Cd contents found in PL2 were very high (189.10
      and 79.49 mg.kg-1 in the RC (rice with Cd) and RBC roots, respectively), the Cd
      accumulated inside the rice seeds at densities of only 3.10 and 1.31 mg.kg-1,
      respectively; thus, the bacteria reduced the Cd content to 57.74% of the control
      content. Therefore, the colonizing bacteria likely acted as an inhibitor of Cd
      translocation in PL2.

PMID- 29211975
TI  - Moving Toward the Future in the Diagnosis of Mental Disorders.

PMID- 29211974
TI  - Three Approaches to Understanding and Classifying Mental Disorder: ICD-11, DSM-5,
      and the National Institute of Mental Health's Research Domain Criteria (RDoC).
AB  - The diagnosis of mental disorder initially appears relatively straightforward:
      Patients present with symptoms or visible signs of illness; health professionals
      make diagnoses based primarily on these symptoms and signs; and they prescribe
      medication, psychotherapy, or both, accordingly. However, despite a dramatic
      expansion of knowledge about mental disorders during the past half century,
      understanding of their components and processes remains rudimentary. We provide
      histories and descriptions of three systems with different purposes relevant to
      understanding and classifying mental disorder. Two major diagnostic manuals-the
      International Classification of Diseases and the Diagnostic and Statistical
      Manual of Mental Disorders-provide classification systems relevant to public
      health, clinical diagnosis, service provision, and specific research
      applications, the former internationally and the latter primarily for the United
      States. In contrast, the National Institute of Mental Health's Research Domain
      Criteria provides a framework that emphasizes integration of basic behavioral and
      neuroscience research to deepen the understanding of mental disorder. We identify
      four key issues that present challenges to understanding and classifying mental
      disorder: etiology, including the multiple causality of mental disorder; whether
      the relevant phenomena are discrete categories or dimensions; thresholds, which
      set the boundaries between disorder and nondisorder; and comorbidity, the fact
      that individuals with mental illness often meet diagnostic requirements for
      multiple conditions. We discuss how the three systems' approaches to these key
      issues correspond or diverge as a result of their different histories, purposes,
      and constituencies. Although the systems have varying degrees of overlap and
      distinguishing features, they share the goal of reducing the burden of suffering
      due to mental disorder.

PMID- 29211976
TI  - Erratum.

PMID- 29211977
TI  - Waste Not, Want Not: Lactate Oxidation Fuels the TCA Cycle.
AB  - Previous studies have demonstrated that mitochondrial respiration is essential
      for tumorigenesis. Hui et al. (2017) and Faubert et al. (2017) demonstrate that
      lactate, traditionally viewed as a waste product of anaerobic and aerobic
      glycolysis, is a major carbon source to fuel the mitochondrial TCA cycle in
      normal tissue and in tumors.

PMID- 29211978
TI  - RevAMPing Mitochondrial Shape to Live Longer.
AB  - Whether and how mitochondria connect reduced energy intake to healthy aging are
      unclear. In this issue of Cell Metabolism, Weir et al. (2017) find that
      constitutive AMPK activation and dietary restriction promote longevity in C.
      elegans via remodeling of the mitochondrial network and fatty acid oxidation in
      peripheral tissues.

PMID- 29211979
TI  - Transcriptional Noise and Somatic Mutations in the Aging Pancreas.
AB  - The underlying mechanisms and functional significance of pancreatic beta cell
      heterogeneity are an intensive area of investigation. In a recent Cell paper,
      Enge and colleagues (2017) performed single-cell RNA sequencing of human
      pancreatic cells and concluded that with age, pancreatic cells become
      transcriptionally noisy and accumulate somatic mutations.

PMID- 29211980
TI  - When Cancer Cells Are Given Lemo[NH3]s, They Make Lemo[NH3]ade.
AB  - In normal physiology, end-products of metabolism are excreted from the body. In
      tumors, these metabolic wastes accumulate due to deregulated metabolism and
      vascular insufficiency. Spinelli et al. (2017) show that breast cancer cells
      adapt to ammonia buildup by recycling it for amino acid synthesis, which can
      support cancer cell growth.

PMID- 29211981
TI  - MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes.
AB  - Type 1 diabetes (T1D) is a multifactorial autoimmune disease whose etiology
      involves complex interactions between the immune system and the intestinal
      microbiota. Recent studies by Rouxel et al. (2017) suggest that innate-like
      mucosal-associated invariant T cells (MAIT cells) may link gut integrity, the
      microbiota, and T1D.

PMID- 29211982
TI  - Structural Insight into a Fatty-Acyl Chaperone for Wnt Proteins.
AB  - Wnt signaling proteins are fatty-acylated and bind to the protein afamin. The
      afamin-Wnt complex increases Wnt solubility dramatically and is likely involved
      in Wnt trafficking. In this issue of Structure, Naschberger et al. (2017)
      determine the crystal structure of afamin in complex with palmitoleic acid,
      revealing how afamin binds palmitoleoylated Wnt.

PMID- 29211983
TI  - How and Why Chaperone-Usher Pilus Rods Stretch.
AB  - Type 1 and P pili are important virulence factors of uropathogenic Escherichia
      coli, the leading cause of urinary tract infections. In this issue of Structure,
      Hospenthal et al. (2017) describe a near-atomic resolution cryo-EM structure of
      the type 1 pilus rod, providing molecular insights into rod uncoiling in two
      pili.

PMID- 29211984
TI  - Promiscuous Protein Binding as a Function of Protein Stability.
AB  - Proteins have evolved to balance efficient binding of desired partners with
      rejection of unwanted interactions. To investigate the evolution of protein
      protein interactions, we selected a random library of pre-stabilized TEM1 beta
      lactamase against wild-type TEM1 using yeast surface display. Three mutations
      were sufficient to achieve micromolar affinity binding between the two. The X-ray
      structure emphasized that the main contribution of the selected mutations was to
      modify the protein fold, specifically removing the N'-terminal helix, which
      consequently allowed protein coupling via a beta-sheet-mediated interaction
      resembling amyloid interaction mode. The only selected mutation located at the
      interaction interface (E58V) is reminiscent of the single mutation commonly
      causing sickle-cell anemia. Interestingly, the evolved mutations cannot be
      inserted into the wild-type protein due to reduced thermal stability of the
      resulting mutant protein. These results reveal a simple mechanism by which
      undesirable binding is purged by loss of thermal stability.

PMID- 29211985
TI  - The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide
      Binding Domain.
AB  - Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for
      genome replication or virion assembly. PIP-binding motifs of cellular proteins do
      not exist in viral proteins. Molecular-docking simulations revealed a putative
      site of PIP binding to poliovirus (PV) 3C protein that was validated using
      nuclear magnetic resonance spectroscopy. The PIP-binding site was located on a
      highly dynamic alpha helix, which also functions in RNA binding. Broad PIP
      binding activity was observed in solution using a fluorescence polarization assay
      or in the context of a lipid bilayer using an on-chip, fluorescence assay. All
      atom molecular dynamics simulations of the 3C protein-membrane interface revealed
      PIP clustering and perhaps PIP-dependent conformations. PIP clustering was
      mediated by interaction with residues that interact with the RNA phosphodiester
      backbone. We conclude that 3C binding to membranes will be determined by PIP
      abundance. We suggest that the duality of function observed for 3C may extend to
      RNA-binding proteins of other viruses.

PMID- 29211986
TI  - tRNA Fluctuations Observed on Stalled Ribosomes Are Suppressed during Ongoing
      Protein Synthesis.
AB  - The pretranslocation complex of the ribosome can undergo spontaneous fluctuations
      of messenger RNA and transfer RNAs (tRNAs) between classical and hybrid states,
      and occupation of the hybrid tRNA positions has been proposed to precede
      translocation. The classical and hybrid state tRNA positions have been
      extensively characterized when the ribosome is stalled along the messenger RNA by
      either the absence or delayed addition of elongation factor G (EF-G), or by the
      presence of antibiotics or GTP analogs that block translocation. However, during
      multiple ongoing elongation cycles when both EF-G and ternary complexes are
      present, EF-G can bind to the pretranslocation complex much faster than the
      timescale of the classic-hybrid transitions. Using single-molecule fluorescence
      resonance energy transfer between adjacent tRNAs and between A-site tRNA and
      ribosomal protein L11, we found that the tRNAs do not fluctuate between the
      hybrid and classical states, but instead adopt a position with fluorescence
      resonance energy transfer efficiencies between those of the stalled classical and
      hybrid states.

PMID- 29211987
TI  - Crystal Structures of Cyanine Fluorophores Stacked onto the End of Double
      Stranded RNA.
AB  - The indodicarbocyanine fluorophores Cy3 and Cy5 are extensively used as donor
      acceptor pairs in fluorescence resonance energy transfer experiments, especially
      those involving single molecules. When terminally attached to double-stranded
      nucleic acids via the 5' phosphate group these fluorophores stack onto the ends
      of the molecule. Knowledge of the positions of the fluorophores is critical to
      the interpretation of fluorescence resonance energy transfer data. The positions
      have been demonstrated for double-stranded (ds) DNA using NMR spectroscopy. Here,
      we have used x-ray crystallography to analyze the location of Cy3 and Cy5 on
      dsRNA, using complexes of an RNA stem-loop bound to L5 protein determined at 2.4
      A resolution. This confirms the tendency of both fluorophores to stack on the
      free end of RNA, with the long axis of the fluorophores approximately parallel to
      that of the terminal basepair. However, the manner of interaction of both Cy3 and
      Cy5 with the terminus of the dsRNA is significantly different from that deduced
      for dsDNA using NMR. The fluorophores are stacked on the terminal basepair such
      that their indole nitrogen atoms lie on the major groove side, and thus their
      pendant methyl groups are on the minor groove side.

PMID- 29211988
TI  - Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of
      Macromolecular Structures.
AB  - Modeling of macromolecular structures involves structural sampling guided by a
      scoring function, resulting in an ensemble of good-scoring models. By necessity,
      the sampling is often stochastic, and must be exhaustive at a precision
      sufficient for accurate modeling and assessment of model uncertainty. Therefore,
      the very first step in analyzing the ensemble is an estimation of the highest
      precision at which the sampling is exhaustive. Here, we present an objective and
      automated method for this task. As a proxy for sampling exhaustiveness, we
      evaluate whether two independently and stochastically generated sets of models
      are sufficiently similar. The protocol includes testing 1) convergence of the
      model score, 2) whether model scores for the two samples were drawn from the same
      parent distribution, 3) whether each structural cluster includes models from each
      sample proportionally to its size, and 4) whether there is sufficient structural
      similarity between the two model samples in each cluster. The evaluation also
      provides the sampling precision, defined as the smallest clustering threshold
      that satisfies the third, most stringent test. We validate the protocol with the
      aid of enumerated good-scoring models for five illustrative cases of binary
      protein complexes. Passing the proposed four tests is necessary, but not
      sufficient for thorough sampling. The protocol is general in nature and can be
      applied to the stochastic sampling of any set of models, not just structural
      models. In addition, the tests can be used to stop stochastic sampling as soon as
      exhaustiveness at desired precision is reached, thereby improving sampling
      efficiency; they may also help in selecting a model representation that is
      sufficiently detailed to be informative, yet also sufficiently coarse for
      sampling to be exhaustive.

PMID- 29211989
TI  - Allosteric Control of a Plant Receptor Kinase through S-Glutathionylation.
AB  - Growing evidence supports the importance of protein S-glutathionylation as a
      regulatory post-translational modification with functional consequences for
      proteins. Discoveries of redox-state-dependent protein kinase S-glutathionylation
      have fueled discussion of redox-sensitive signaling. Following previously
      published experimental evidence for S-glutathionylation induced deactivation of
      the Arabidopsis thaliana kinase BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR
      LIKE KINASE 1 (BAK1), we investigated the consequences of S-glutathionylation on
      the equilibrium conformational ensemble of BAK1 using all-atom molecular dynamics
      simulations. We found that glutathionylation of C408 allosterically destabilizes
      the active-like state of BAK1 and stabilizes an inactive conformation known to
      recur in protein kinases. Glutathionylation of C408 also has structural
      consequences throughout the BAK1 kinase domain, whereas glutathionylation of C353
      in the N-lobe and C374 near the ATP-binding site have few notable effects on BAK1
      compared with the unmodified protein. Our results suggest an allosteric mechanism
      for inhibition of BAK1 by C408 S-glutathionylation, and more generally, support
      the notion of protein kinase S-glutathionylation as a means of redox signaling in
      plant cells.

PMID- 29211990
TI  - The Photosystem II Subunit S under Stress.
AB  - Nonphotochemical quenching is the protective mechanism against overexcitation of
      photosystem II, triggered by excess DeltapH in photosynthetic membranes. The
      light-harvesting complexes (LHCs), the de-epoxidation of violaxanthin to
      zeaxanthin, and the photosystem II subunit S (PsbS) work in synergy for an
      optimized multilevel response. Understanding the fine details of this synergy has
      proven challenging to scientific research. Here, we employ large-scale, all-atom
      molecular simulations and beyond experimental insight, we proceed a step further
      in identifying the PsbS dynamics that could possibly be associated with this
      synergy. For the first time, to our knowledge, we probe the distinct behavior of
      PsbS under DeltapH that probes the details of the potential dimer-to-monomer
      transition, and in a violaxanthin/zeaxanthin-rich membrane, at an all-atom
      resolution. We propose that the lumen-exposed residues, threonine 162 and
      glutamic acid 173, form stabilizing hydrogen bonds between the PsbS monomers only
      at high lumen pH, whereas at low pH (excess DeltapH) this interaction is lost,
      and leads to higher flexibility of the protein and potentially to the dimer-to
      monomer transition. Lastly, we discuss how conformational changes under the
      presence of DeltapH/zeaxanthin are related to the PsbS role in the current
      nonphotochemical quenching model in the literature. For the latter, we probe a
      PsbS-monomeric LHCII association. The association is proposed to potentially
      alter the monomeric LHCII sensitivity to DeltapH by changing the pKa values of
      interacting LHCII residues. This serves as an example where protonation-ligation
      events enhance protein-protein interactions fundamental to many life processes.

PMID- 29211991
TI  - Low-Resolution Structure of Detergent-Solubilized Membrane Proteins from Small
      Angle Scattering Data.
AB  - Despite the ever-increasing usage of small-angle scattering as a valuable
      complementary method in the field of structural biology, applications concerning
      membrane proteins remain elusive mainly due to experimental challenges and the
      relative lack of theoretical tools for the treatment of scattering data. This
      fact adds up to general difficulties encountered also by other established
      methods (crystallography, NMR) for the study of membrane proteins. Following the
      general paradigm of ab initio methods for low-resolution restoration of soluble
      protein structure from small-angle scattering data, we construct a general
      multiphase model with a set of physical constraints, which, together with an
      appropriate minimization procedure, gives direct structural information
      concerning the different components (protein, detergent molecules) of detergent
      solubilized membrane protein complexes. Assessment of the method's precision and
      robustness is evaluated by performing shape restorations from simulated data of a
      tetrameric alpha-helical membrane channel (Aquaporin-0) solubilized by n-Dodecyl
      beta-D-Maltoside and from previously published small-angle neutron scattering
      experimental data of the filamentous hemagglutinin adhesin beta-barrel protein
      transporter solubilized by n-Octyl beta-D-glucopyranoside. It is shown that the
      acquisition of small-angle neutron scattering data at two different solvent
      contrasts, together with an estimation of detergent aggregation number around the
      protein, permits the reliable reconstruction of the shape of membrane proteins
      without the need for any prior structural information.

PMID- 29211992
TI  - Fluctuation Analysis in Nonstationary Conditions: Single Ca2+ Channel Current in
      Pyramidal Neurons.
AB  - Fluctuation analysis is a method that allows measurement of the single-channel
      current of ion channels even when it is too small to be resolved directly with
      the patch-clamp technique. This is the case for voltage-gated calcium channels.
      They are present in all mammalian central neurons, controlling presynaptic
      release of transmitter, postsynaptic signaling, and synaptic integration. The
      amplitudes of their single-channel currents in a physiological concentration of
      extracellular calcium, however, are small and not well determined. But
      measurement of this quantity is essential for estimating numbers of functional
      voltage-gated calcium channels in the membrane and the size of channel-associated
      calcium signaling domains, and for understanding the stochastic nature of calcium
      signaling. Here, we recorded the voltage-gated calcium channel current in
      nucleated patches from layer 5 pyramidal neurons in rat neocortex, in
      physiological external calcium (1-2 mM). The ensemble-averaging of current
      responses required for conventional fluctuation analysis proved impractical
      because of the rapid rundown of calcium channel currents. We therefore developed
      a more robust method, using mean current fitting of individual current responses
      and band-pass filtering. Furthermore, voltage-ramp stimulation proved useful. We
      validated the accuracy of the method by analyzing simulated data. At an external
      calcium concentration of 1 mM, and a membrane potential of -20 mV, we found that
      the average single-channel current amplitude was ~0.04 pA, increasing to 0.065 pA
      at 2 mM external calcium, and 0.12 pA at 5 mM. The relaxation time constant of
      the fluctuations was in the range 0.2-0.8 ms. The results are relevant to
      understanding the stochastic properties of dendritic Ca2+ spikes in neocortical
      layer 5 pyramidal neurons. With the reported method, single-channel current
      amplitude of native voltage-gated calcium channels can be resolved accurately
      despite conditions of unstable rundown.

PMID- 29211993
TI  - Single-Molecule Study Reveals How Receptor and Ras Synergistically Activate
      PI3Kalpha and PIP3 Signaling.
AB  - Cellular pathways controlling chemotaxis, growth, survival, and oncogenesis are
      activated by receptor tyrosine kinases and small G-proteins of the Ras
      superfamily that stimulate specific isoforms of phosphatidylinositol-3-kinase
      (PI3K). These PI3K lipid kinases phosphorylate the constitutive lipid
      phosphatidylinositol-4,5-bisphosphate (PIP2) to produce the signaling lipid
      phosphatidylinositol-3,4,5-trisphosphate (PIP3). Progress has been made in
      understanding direct, moderate PI3K activation by receptors. In contrast, the
      mechanism by which receptors and Ras synergistically activate PI3K to much higher
      levels remains unclear, and two competing models have been proposed: membrane
      recruitment versus activation of the membrane-bound enzyme. To resolve this
      central mechanistic question, this study employs single-molecule imaging to
      investigate PI3K activation in a six-component pathway reconstituted on a
      supported lipid bilayer. The findings reveal that simultaneous activation by a
      receptor activation loop (from platelet-derived growth factor receptor, a
      receptor tyrosine kinase) and H-Ras generates strong, synergistic activation of
      PI3Kalpha, yielding a large increase in net kinase activity via the membrane
      recruitment mechanism. Synergy requires receptor phospho-Tyr and two anionic
      lipids (phosphatidylserine and PIP2) to make PI3Kalpha competent for bilayer
      docking, as well as for subsequent binding and phosphorylation of substrate PIP2
      to generate product PIP3. Synergy also requires recruitment to membrane-bound H
      Ras, which greatly speeds the formation of a stable, membrane-bound PI3Kalpha
      complex, modestly slows its off rate, and dramatically increases its equilibrium
      surface density. Surprisingly, H-Ras binding significantly inhibits the specific
      kinase activity of the membrane-bound PI3Kalpha molecule, but this minor enzyme
      inhibition is overwhelmed by the marked enhancement of membrane recruitment. The
      findings have direct impacts for the fields of chemotaxis, innate immunity,
      inflammation, carcinogenesis, and drug design.

PMID- 29211994
TI  - Membrane Tension Inhibits Rapid and Slow Endocytosis in Secretory Cells.
AB  - Endocytosis generates spherical or ellipsoid-like vesicles from the plasma
      membrane, which recycles vesicles that fuse with the plasma member during
      exocytosis in neurons and endocrine secretory cells. Although tension in the
      plasma membrane is generally considered to be an important factor in regulating
      endocytosis, whether membrane tension inhibits or facilitates endocytosis remains
      debated in the endocytosis field, and has been rarely studied for vesicular
      endocytosis in secretory cells. Here we report that increasing membrane tension
      by adjusting osmolarity inhibited both the rapid (a few seconds) and slow (tens
      of seconds) endocytosis in calyx-type nerve terminals containing conventional
      active zones and in neuroendocrine chromaffin cells. We address the mechanism of
      this phenomenon by computational modeling of the energy barrier that the system
      must overcome at the stage of membrane budding by an assembling protein coat. We
      show that this barrier grows with increasing tension, which may slow down or
      prevent membrane budding. These results suggest that in live secretory cells,
      membrane tension exerts inhibitory action on endocytosis.

PMID- 29211995
TI  - Identification of Two New Cholesterol Interaction Sites on the A2A Adenosine
      Receptor.
AB  - By mole, cholesterol is the most abundant component of animal cell plasma
      membranes. Many membrane proteins have been shown to be functionally dependent on
      cholesterol, several of which have also been shown to bind cholesterol at well
      defined locations on their membrane-facing surface. In this work, a combination
      of coarse-grained "Martini" and all-atom simulations are used to identify two, to
      our knowledge, new cholesterol-binding sites on the A2A adenosine receptor, a G
      protein-coupled receptor that is a target for the treatment of Parkinson's
      disease. One of the sites is also observed to bind cholesterol in several recent,
      high-resolution crystal structures of the protein, and in the simulations,
      interacts with cholesterol only when bound to the inverse agonist ZM241385.
      Cataloguing cholesterol-binding sites is a vital step in the effort to understand
      cholesterol-dependent function of membrane proteins. Given that cholesterol
      content in plasma membranes varies with cell type and on administration of widely
      prescribed pharmaceuticals, such as statins, understanding cholesterol-dependent
      function is an important step toward exploiting membrane compositional variation
      for therapeutic purposes.

PMID- 29211996
TI  - Hallmarks of Reversible Separation of Living, Unperturbed Cell Membranes into Two
      Liquid Phases.
AB  - Controversy has long surrounded the question of whether spontaneous lateral
      demixing of membranes into coexisting liquid phases can organize proteins and
      lipids on micron scales within unperturbed, living cells. A clear answer hinges
      on observation of hallmarks of a reversible phase transition. Here, by directly
      imaging micron-scale membrane domains of yeast vacuoles both in vivo and cell
      free, we demonstrate that the domains arise through a phase separation mechanism.
      The domains are large, have smooth boundaries, and can merge quickly, consistent
      with fluid phases. Moreover, the domains disappear above a distinct miscibility
      transition temperature (Tmix) and reappear below Tmix, over multiple heating and
      cooling cycles. Hence, large-scale membrane organization in living cells under
      physiologically relevant conditions can be controlled by tuning a single
      thermodynamic parameter.

PMID- 29211997
TI  - Challenges in Estimating the Motility Parameters of Single Processive Motor
      Proteins.
AB  - Cytoskeletal motor proteins are essential to the function of a wide range of
      intracellular mechano-systems. The biophysical characterization of their movement
      along their filamentous tracks is therefore of large importance. Toward this end,
      single-molecule, in vitro stepping-motility assays are commonly used to determine
      motor velocity and run length. However, comparing results from such experiments
      has proved difficult due to influences from variations in the experimental
      conditions and the data analysis methods. Here, we investigate the movement of
      fluorescently labeled, processive, dimeric motor proteins and propose a unified
      algorithm to correct the measurements for finite filament length as well as
      photobleaching. Particular emphasis is put on estimating the statistical errors
      associated with the proposed evaluation method, as knowledge of these values is
      crucial when comparing measurements from different experiments. Testing our
      approach with simulated and experimental data from GFP-labeled kinesin-1 motors
      stepping along immobilized microtubules, we show 1) that velocity distributions
      should be fitted by a t location-scale probability density function rather than
      by a normal distribution; 2) that the impossibility to measure events shorter
      than the image acquisition time needs to be taken into account; 3) that the
      interaction time and run length of the motors can be estimated independent of the
      filament length distribution; and 4) that the dimeric nature of the motors needs
      to be considered when correcting for photobleaching. Moreover, our analysis
      reveals that controlling the temperature during the experiments with a precision
      below 1 K is of importance. We believe our method will not only improve the
      evaluation of experimental data, but also allow for better statistical
      comparisons between different populations of motor proteins (e.g., with distinct
      mutations or linked to different cargos) and filaments (e.g., in distinct
      nucleotide states or with different posttranslational modifications). Therefore,
      we include a detailed workflow for image processing and analysis (including
      MATLAB code), serving as a tutorial for the estimation of motility parameters in
      stepping-motility assays.

PMID- 29211998
TI  - Tropomyosin Must Interact Weakly with Actin to Effectively Regulate Thin Filament
      Function.
AB  - Elongated tropomyosin, associated with actin-subunits along the surface of thin
      filaments, makes electrostatic interactions with clusters of conserved residues,
      K326, K328, and R147, on actin. The association is weak, permitting low-energy
      cost regulatory movement of tropomyosin across the filament during muscle
      activation. Interestingly, acidic D292 on actin, also evolutionarily conserved,
      lies adjacent to the three-residue cluster of basic amino acids and thus may
      moderate the combined local positive charge, diminishing tropomyosin-actin
      interaction and facilitating regulatory-switching. Indeed, charge neutralization
      of D292 is connected to muscle hypotonia in individuals with D292V actin
      mutations and linked to congenital fiber-type disproportion. Here, the D292V
      mutation may predispose tropomyosin-actin positioning to a myosin-blocking state,
      aberrantly favoring muscle relaxation, thus mimicking the low-Ca2+ effect of
      troponin even in activated muscles. To test this hypothesis, interaction
      energetics and in vitro function of wild-type and D292V filaments were measured.
      Energy landscapes based on F-actin-tropomyosin models show the mutation localizes
      tropomyosin in a blocked-state position on actin defined by a deeper energy
      minimum, consistent with augmented steric-interference of actin-myosin binding.
      In addition, whereas myosin-dependent motility of troponin/tropomyosin-free D292V
      F-actin is normal, motility is dramatically inhibited after addition of
      tropomyosin to the mutant actin. Thus, D292V-induced blocked-state stabilization
      appears to disrupt the delicately poised energy balance governing thin filament
      regulation. Our results validate the premise that stereospecific but necessarily
      weak binding of tropomyosin to F-actin is required for effective thin filament
      function.

PMID- 29212000
TI  - Is Aggregate-Dependent Yeast Aging Fortuitous? A Model of Damage Segregation and
      Aggregate Dynamics.
AB  - During cytokinesis in Saccharomyces cerevisiae, damaged proteins are distributed
      unequally between the daughter and mother cells. The retention of these proteins
      is correlated with yeast aging. Even though evidence suggests that aggregates are
      retained due to an underlying molecular mechanism, the debate on whether an
      active mechanism is necessary for this asymmetry remains unsolved. In particular,
      passive diffusion and a bud-specific dilution remain as possible explanations.
      Here, a computational and mathematical model is provided to test whether passive
      mechanisms alone are sufficient to account for the aggregate distribution
      patterns and the aggregate kinetics observed in living cells. To this author's
      knowledge, this is the most comprehensive model available on this subject and the
      only one combining key potentially essential passive-only mechanisms proposed in
      existing bibliography-namely, the geometrical effect of the dividing yeast cell
      on the diffusion of protein aggregates, and the possibility of aggregate binding
      and aggregate formation at different rates. Results suggest that although passive
      processes alone can reproduce certain averaged observables from experimental
      bibliography, they are insufficient to vindicate aggregate activity observed in
      living budding yeast cells. These results are complemented by showing that under
      basic forms of active quality control, discrepancies between the outputs of the
      model and experimental bibliography are reduced.

PMID- 29211999
TI  - A Simple and Powerful Analysis of Lateral Subdiffusion Using Single Particle
      Tracking.
AB  - In biological membranes, many factors such as cytoskeleton, lipid composition,
      crowding, and molecular interactions deviate lateral diffusion from the expected
      random walks. These factors have different effects on diffusion but act
      simultaneously, so the observed diffusion is a complex mixture of diffusive
      behaviors (directed, Brownian, anomalous, or confined). Therefore, commonly used
      approaches to quantify diffusion based on averaging of the displacements such as
      the mean square displacement, are not adapted to the analysis of this
      heterogeneity. We introduce a parameter-the packing coefficient Pc, which gives
      an estimate of the degree of free movement that a molecule displays in a period
      of time independently of its global diffusivity. Applying this approach to two
      different situations (diffusion of a lipid probe and trapping of receptors at
      synapses), we show that Pc detected and localized temporary changes of diffusive
      behavior both in time and in space. More importantly, it allowed the detection of
      periods with very high confinement as well as their frequency and duration, and
      thus it can be used to calculate the effective kon and koff of scaffolding
      interactions such as those that immobilize receptors at synapses.

PMID- 29212001
TI  - Mechanism of Kin-Discriminatory Demarcation Line Formation between Colonies of
      Swarming Bacteria.
AB  - Swarming bacteria use kin discrimination to preferentially associate with their
      clonemates for certain cooperative behaviors. Kin discrimination can manifest as
      an apparent demarcation line (a region lacking cells or with much lower cell
      density) between antagonist strains swarming toward each other. In contrast, two
      identical strains merge with no demarcation. Experimental studies suggest contact
      dependent killing between different strains as a mechanism of kin discrimination,
      but it is not clear whether this killing is sufficient to explain the observed
      patterns. Here, we investigate the formation of demarcation line with a
      mathematical model. First, using data from competition experiments between kin
      discriminating strains of Myxococcus xanthus and Proteus mirabilis, we found the
      rates of killing between the strains to be highly asymmetric, i.e., one strain
      kills another at a much higher rate. Then, to investigate how such asymmetric
      interactions can lead to a stable demarcation line, we construct reaction
      diffusion models for colony expansion of kin-discriminatory strains. Our results
      demonstrate that a stable demarcation line can form when both cell movement and
      cell growth cease at low nutrient levels. Further, our study suggests that,
      depending on the initial separation between the inoculated colonies, the
      demarcation line may move transiently before stabilizing. We validated these
      model predictions by observing dynamics of merger between two M. xanthus strains,
      where one strain expresses a toxin protein that kills a second strain lacking the
      corresponding antitoxin. Our study therefore provides a theoretical understanding
      of demarcation line formation between kin-discriminatory populations, and can be
      used for analyzing and designing future experiments.

PMID- 29212002
TI  - Going with the Flow: Water Flux and Cell Shape during Cytokinesis.
AB  - Cell shape changes during cytokinesis in eukaryotic cells have been attributed to
      contractile forces from the actomyosin ring and the actomyosin cortex. Here we
      propose an additional mechanism where active pumping of ions and water at the
      cell poles and the division furrow can also achieve the same type of shape change
      during cytokinesis without myosin contraction. We develop a general mathematical
      model to examine shape changes in a permeable object subject to boundary fluxes.
      We find that hydrodynamic flows in the cytoplasm and the relative drag between
      the cytoskeleton network phase and the water phase also play a role in
      determining the cell shape during cytokinesis. Forces from the actomyosin
      contractile ring and cortex do contribute to the cell shape, and can work
      together with water permeation to facilitate cytokinesis. To influence water
      flow, we osmotically shock the cell during cell division, and find that the cell
      can actively adapt to osmotic changes and complete division. Depolymerizing the
      actin cytoskeleton during cytokinesis also does not affect the contraction speed.
      We also explore the role of membrane ion channels and pumps in setting up the
      spatially varying water flux.

PMID- 29212003
TI  - SOCE Is Important for Maintaining Sarcoplasmic Calcium Content and Release in
      Skeletal Muscle Fibers.
AB  - Store-operated Ca2+ entry (SOCE) is a Ca2+-entry process activated by the
      depletion of intracellular stores and has an important role in many cell types.
      In skeletal muscle, however, its role during physiological muscle activation has
      been controversial. To address this question, sarcoplasmic reticulum (SR) calcium
      release in a mouse strain with a naturally occurring mutation in the myostatin
      gene (Compact (Cmpt)) leading to a hypermuscular yet reduced muscle-force
      phenotype was compared to that in wild-type mice. To elicit Ca2+ release from the
      SR of flexor digitorum brevis (FDB) fibers, either a ryanodine receptor agonist
      (4-chloro-meta-cresol) or depolarizing pulses were used. In muscles from Cmpt
      mice, endogenous protein levels of STIM1 and Orai1 were reduced, and
      consequently, SOCE after 4-chloro-meta-cresol-induced store depletion was
      suppressed. Although the voltage dependence of SR calcium release was not
      statistically different between wild-type and Cmpt fibers, the amount of
      releasable calcium was significantly reduced in the latter, indicating a smaller
      SR content. To assess the immediate role of SOCE in replenishing the SR calcium
      store, the evolution of intracellular calcium concentration during a train of
      long-lasting depolarizations to a maximally activating voltage was monitored.
      Cmpt mice exhibited a faster decline in calcium release, suggesting a compromised
      ability to refill the SR. A simple model that incorporates a reduced SOCE as an
      important partner in regulating immediate calcium influx through the surface
      membrane readily accounts for the steady-state reduction in SR calcium content
      and its more pronounced decline after calcium release.

PMID- 29212004
TI  - Investigating Focal Adhesion Substructures by Localization Microscopy.
AB  - Cells rely on focal adhesions (FAs) to carry out a variety of important tasks,
      including motion, environmental sensing, and adhesion to the extracellular
      matrix. Although attaining a fundamental characterization of FAs is a compelling
      goal, their extensive complexity and small size, which can be below the
      diffraction limit, have hindered a full understanding. In this study we have used
      single-molecule localization microscopy (SMLM) to investigate integrin beta3 and
      paxillin in rat embryonic fibroblasts growing on two different extracellular
      matrix-representing substrates (i.e., fibronectin-coated substrates and
      specifically biofunctionalized nanopatterned substrates). To quantify the
      substructure of FAs, we developed a clustering method based on expectation
      maximization of a Gaussian mixture that accounts for localization uncertainty and
      background. Analysis of our SMLM data indicates that the structures within FAs,
      characterized as a Gaussian mixture, typically have areas between 0.01 and 1
      MUm2, contain 10-100 localizations, and can exhibit substantial eccentricity. Our
      approach based on SMLM opens new avenues for studying structural and functional
      biology of molecular assemblies that display substantial varieties in size,
      shape, and density.

PMID- 29212005
TI  - Desmoglein 3 Order and Dynamics in Desmosomes Determined by Fluorescence
      Polarization Microscopy.
AB  - Desmosomes are macromolecular cell-cell junctions that provide adhesive strength
      in epithelial tissue. Desmosome function is inseparably linked to structure, and
      it is hypothesized that the arrangement, or order, of desmosomal cadherins in the
      intercellular space is critical for adhesive strength. However, due to desmosome
      size, molecular complexity, and dynamics, the role that order plays in adhesion
      is challenging to study. Herein, we present an excitation resolved fluorescence
      polarization microscopy approach to measure the spatiotemporal dynamics of order
      and disorder of the desmosomal cadherin desmoglein 3 (Dsg3) in living cells.
      Simulations were used to establish order factor as a robust metric for
      quantifying the spatiotemporal dynamics of order and disorder. Order factor
      measurements in keratinocytes showed the Dsg3 extracellular domain is ordered at
      the individual desmosome, single cell, and cell population levels compared to a
      series of disordered controls. Desmosomal adhesion is Ca2+ dependent, and
      reduction of extracellular Ca2+ leads to a loss of adhesion measured by dispase
      fragmentation assay (lambda = 15.1 min). Live cell imaging revealed Dsg3 order
      decreased more rapidly (lambda = 5.5 min), indicating that cadherin order is not
      required for adhesion. Our results suggest that rapid disordering of cadherins
      can communicate a change in extracellular Ca2+ concentration to the cell, leading
      to a downstream loss of adhesion. Fluorescence polarization is an effective
      bridge between protein structure and complex dynamics and the approach presented
      here is broadly applicable to studying order in macromolecular structures.

PMID- 29212006
TI  - Reconstruction of Cell Focal Adhesions using Physical Constraints and Compressive
      Regularization.
AB  - We develop a method to reconstruct, from measured displacements of an underlying
      elastic substrate, the spatially dependent forces that cells or tissues impart on
      it. Given newly available high-resolution images of substrate displacements, it
      is desirable to be able to reconstruct small-scale, compactly supported focal
      adhesions that are often localized and exist only within the footprint of a cell.
      In addition to the standard quadratic data mismatch terms that define least
      squares fitting, we motivate a regularization term in the objective function that
      penalizes vectorial invariants of the reconstructed surface stress while
      preserving boundaries. We solve this inverse problem by providing a numerical
      method for setting up a discretized inverse problem that is solvable by standard
      convex optimization techniques. By minimizing the objective function subject to a
      number of important physically motivated constraints, we are able to efficiently
      reconstruct stress fields with localized structure from simulated and
      experimental substrate displacements. Our method incorporates the exact solution
      for a stress tensor accurate to first-order finite differences and motivates the
      use of distance-based cutoffs for data inclusion and problem sparsification.

PMID- 29212007
TI  - Ultrahigh-Resolution Optical Coherence Elastography Images Cellular-Scale
      Stiffness of Mouse Aorta.
AB  - Cellular-scale imaging of the mechanical properties of tissue has helped to
      reveal the origins of disease; however, cellular-scale resolution is not readily
      achievable in intact tissue volumes. Here, we demonstrate volumetric imaging of
      Young's modulus using ultrahigh-resolution optical coherence elastography, and
      apply it to characterizing the stiffness of mouse aortas. We achieve isotropic
      resolution of better than 15 MUm over a 1-mm lateral field of view through the
      entire depth of an intact aortic wall. We employ a method of quasi-static
      compression elastography that measures volumetric axial strain and uses a
      compliant, transparent layer to measure surface axial stress. This combination is
      used to estimate Young's modulus throughout the volume. We demonstrate
      differentiation by stiffness of individual elastic lamellae and vascular smooth
      muscle. We observe stiffening of the aorta in regulator of G protein signaling 5
      deficient mice, a model that is linked to vascular remodeling and fibrosis. We
      observe increased stiffness with proximity to the heart, as well as regions with
      micro-structural and micro-mechanical signatures characteristic of fibrous and
      lipid-rich tissue. High-resolution imaging of Young's modulus with optical
      coherence elastography may become an important tool in vascular biology and in
      other fields concerned with understanding the role of mechanics within the
      complex three-dimensional architecture of tissue.

PMID- 29212009
TI  - SNARE-Mediated Single-Vesicle Fusion Events with Supported and Freestanding Lipid
      Membranes.

PMID- 29212008
TI  - Stochastic Pacing Inhibits Spatially Discordant Cardiac Alternans.
AB  - Depressed heart rate variability is a well-established risk factor for sudden
      cardiac death in survivors of acute myocardial infarction and for those with
      congestive heart failure. Although measurements of heart rate variability provide
      a valuable prognostic tool, it is unclear whether reduced heart rate variability
      itself is proarrhythmic or if it simply correlates with the severity of autonomic
      nervous system dysfunction. In this work, we investigate a possible mechanism by
      which heart rate variability could protect against cardiac arrhythmia.
      Specifically, in numerical simulations, we observe an inverse relationship
      between the variance of stochastic pacing and the occurrence of spatially
      discordant alternans, an arrhythmia that is widely believed to facilitate the
      development of cardiac fibrillation. By analyzing the effects of conduction
      velocity restitution, cellular dynamics, electrotonic coupling, and stochastic
      pacing on the nodal dynamics of spatially discordant alternans, we provide
      intuition for this observed behavior and propose control strategies to inhibit
      discordant alternans.

PMID- 29212010
TI  - Moving in the Right Direction: Protein Vibrations Steering Function.

PMID- 29212011
TI  - Temperature-Induced Transitions in the Structure and Interfacial Rheology of
      Human Meibum.

PMID- 29212012
TI  - AgRP Accountants Compute Caloric Cost.
AB  - The gut-brain communication underlying energy homeostasis has been a topic of
      interest for years. In two new papers, Beutler et al. (2017) and Su et al. (2017)
      delve into the mechanisms by which satiation is represented in a well-studied
      population of orexigenic neurons.

PMID- 29212013
TI  - Cell Type of Origin Dictates the Route to Pluripotency.
AB  - Our current understanding of induced pluripotent stem cell (iPSC) generation has
      almost entirely been shaped by studies performed on reprogramming fibroblasts.
      However, whether the resulting model universally applies to the reprogramming
      process of other cell types is still largely unknown. By characterizing and
      profiling the reprogramming pathways of fibroblasts, neutrophils, and
      keratinocytes, we unveil that key events of the process, including loss of
      original cell identity, mesenchymal to epithelial transition, the extent of
      developmental reversion, and reactivation of the pluripotency network, are to a
      large degree cell-type specific. Thus, we reveal limitations for the use of
      fibroblasts as a universal model for the study of the reprogramming process and
      provide crucial insights about iPSC generation from alternative cell sources.

PMID- 29212014
TI  - Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent
      Stem Cells.
AB  - Organoid technology provides a revolutionary paradigm toward therapy but has yet
      to be applied in humans, mainly because of reproducibility and scalability
      challenges. Here, we overcome these limitations by evolving a scalable organ bud
      production platform entirely from human induced pluripotent stem cells (iPSC). By
      conducting massive "reverse" screen experiments, we identified three progenitor
      populations that can effectively generate liver buds in a highly reproducible
      manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we
      achieved human scalability by developing an omni-well-array culture platform for
      mass producing homogeneous and miniaturized liver buds on a clinically relevant
      large scale (>108). Vascularized and functional liver tissues generated entirely
      from iPSCs significantly improved subsequent hepatic functionalization
      potentiated by stage-matched developmental progenitor interactions, enabling
      functional rescue against acute liver failure via transplantation. Overall, our
      study provides a stringent manufacturing platform for multicellular organoid
      supply, thus facilitating clinical and pharmaceutical applications especially for
      the treatment of liver diseases through multi-industrial collaborations.

PMID- 29212015
TI  - Opposing Post-transcriptional Control of InR by FMRP and LIN-28 Adjusts Stem Cell
      Based Tissue Growth.
AB  - Although the intrinsic mechanisms that control whether stem cells divide
      symmetrically or asymmetrically underlie tissue growth and homeostasis, they
      remain poorly defined. We report that the RNA-binding protein fragile X mental
      retardation protein (FMRP) limits the symmetric division, and resulting
      expansion, of the stem cell population during adaptive intestinal growth in
      Drosophila. The elevated insulin sensitivity that FMRP-deficient progenitor cells
      display contributes to their accelerated expansion, which is suppressed by the
      depletion of insulin-signaling components. This FMRP activity is mediated solely
      via a second conserved RNA-binding protein, LIN-28, known to boost insulin
      signaling in stem cells. Via LIN-28, FMRP controls progenitor cell behavior by
      post-transcriptionally repressing the level of insulin receptor (InR). This study
      identifies the stem cell-based mechanism by which FMRP controls tissue
      adaptation, and it raises the possibility that defective adaptive growth
      underlies the accelerated growth, gastrointestinal, and other symptoms that
      affect fragile X syndrome patients.

PMID- 29212017
TI  - Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched
      Transcription Factor Foxp2.
AB  - Alteration of corticostriatal glutamatergic function is an early
      pathophysiological change associated with Huntington's disease (HD). The factors
      that regulate the maintenance of corticostriatal glutamatergic synapses post
      developmentally are not well understood. Recently, the striatum-enriched
      transcription factor Foxp2 was implicated in the development of these synapses.
      Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two
      models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2
      in wild-type mice leads to development of HD-associated behaviors. We note that
      Foxp2 encodes the longest polyglutamine repeat protein in the human reference
      genome, and we show that it can be sequestered into aggregates with polyglutamine
      expanded mutant Huntingtin protein (mHTT). Foxp2 overexpression in HD model mice
      leads to altered expression of several genes associated with synaptic function,
      genes that present additional targets for normalization of corticostriatal
      dysfunction in HD.

PMID- 29212016
TI  - Cellular Phenotypes in Human iPSC-Derived Neurons from a Genetic Model of Autism
      Spectrum Disorder.
AB  - A deletion or duplication in the 16p11.2 region is associated with
      neurodevelopmental disorders, including autism spectrum disorder and
      schizophrenia. In addition to clinical characteristics, carriers of the 16p11.2
      copy-number variant (CNV) manifest opposing neuroanatomical phenotypes-e.g.,
      macrocephaly in deletion carriers (16pdel) and microcephaly in duplication
      carriers (16pdup). Using fibroblasts obtained from 16pdel and 16pdup carriers, we
      generated induced pluripotent stem cells (iPSCs) and differentiated them into
      neurons to identify causal cellular mechanisms underlying neurobiological
      phenotypes. Our study revealed increased soma size and dendrite length in 16pdel
      neurons and reduced neuronal size and dendrite length in 16pdup neurons. The
      functional properties of iPSC-derived neurons corroborated aspects of these
      contrasting morphological differences that may underlie brain size.
      Interestingly, both 16pdel and 16pdup neurons displayed reduced synaptic density,
      suggesting that distinct mechanisms may underlie brain size and neuronal
      connectivity at this locus.

PMID- 29212018
TI  - Structure and Function of an Actin-Based Filter in the Proximal Axon.
AB  - The essential organization of microtubules within neurons has been described;
      however, less is known about how neuronal actin is arranged and the functional
      implications of its arrangement. Here, we describe, in live cells, an actin-based
      structure in the proximal axon that selectively prevents some proteins from
      entering the axon while allowing the passage of others. Concentrated patches of
      actin in proximal axons are present shortly after axonal specification in rat and
      zebrafish neurons imaged live, and they mark positions where anterogradely
      traveling vesicles carrying dendritic proteins halt and reverse. Patches
      colocalize with the ARP2/3 complex, and when ARP2/3-mediated nucleation is
      blocked, a dendritic protein mislocalizes to the axon. Patches are highly
      dynamic, with few persisting longer than 30 min. In neurons in culture and in
      vivo, actin appears to form a contiguous, semipermeable barrier, despite its
      apparently sparse distribution, preventing axonal localization of constitutively
      active myosin Va but not myosin VI.

PMID- 29212020
TI  - Mechanotransmission and Mechanosensing of Human alpha-Actinin 1.
AB  - alpha-Actinins, a family of critical cytoskeletal actin-binding proteins that
      usually exist as anti-parallel dimers, play crucial roles in organizing the
      framework of the cytoskeleton through crosslinking the actin filaments, as well
      as in focal adhesion maturation. However, the molecular mechanisms underlying its
      functions are unclear. Here, by mechanical manipulation of single human alpha
      actinin 1 using magnetic tweezers, we determined the mechanical stability and
      kinetics of the functional domains in alpha-actinin 1. Moreover, we identified
      the force-dependence of vinculin binding to alpha-actinin 1, with the
      demonstration that force is required to expose the high-affinity binding site for
      vinculin binding. Further, a role of the alpha-actinin 1 as molecular shock
      absorber for the cytoskeleton network is revealed. Our results provide a
      comprehensive analysis of the force-dependent stability and interactions of alpha
      actinin 1, which sheds important light on the molecular mechanisms underlying its
      mechanotransmission and mechanosensing functions.

PMID- 29212019
TI  - Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed
      by Single-Mitochondrion Sequencing.
AB  - A number of mitochondrial diseases arise from single-nucleotide variant (SNV)
      accumulation in multiple mitochondria. Here, we present a method for
      identification of variants present at the single-mitochondrion level in
      individual mouse and human neuronal cells, allowing for extremely high-resolution
      study of mitochondrial mutation dynamics. We identified extensive heteroplasmy
      between individual mitochondrion, along with three high-confidence variants in
      mouse and one in human that were present in multiple mitochondria across cells.
      The pattern of variation revealed by single-mitochondrion data shows surprisingly
      pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci
      suggests inheritance of variants across generations, resulting in Poisson jackpot
      lines with large SNV load. Comparison of human and mouse variants suggests that
      the two species might employ distinct modes of somatic segregation. Single
      mitochondrion resolution revealed mitochondria mutational dynamics that we
      hypothesize to affect risk probabilities for mutations reaching disease
      thresholds.

PMID- 29212021
TI  - Nutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron
      Activity.
AB  - The brain regulates food intake by processing sensory cues and peripheral
      physiological signals, but the neural basis of this integration remains unclear.
      Hypothalamic, agouti-related protein (AgRP)-expressing neurons are critical
      regulators of food intake. AgRP neuron activity is high during hunger and is
      rapidly reduced by the sight and smell of food. Here, we reveal two distinct
      components of AgRP neuron activity regulation: a rapid but transient sensory
      driven signal and a slower, sustained calorie-dependent signal. We discovered
      that nutrients are necessary and sufficient for sustained reductions in AgRP
      neuron activity and that activity reductions are proportional to the calories
      obtained. This change in activity is recapitulated by exogenous administration of
      gut-derived satiation signals. Furthermore, we showed that the nutritive value of
      food trains sensory systems-in a single trial-to drive rapid, anticipatory AgRP
      neuron activity inhibition. Together, these data demonstrate that nutrients are
      the primary regulators of AgRP neuron activity.

PMID- 29212022
TI  - Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential
      Regulator of Glucose and Lipid Homeostasis.
AB  - The central mechanisms controlling glucose and lipid homeostasis are inadequately
      understood. We show that alpha2delta-1 is an essential regulator of glucose and
      lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial
      hypothalamus (VMH). These effects are body weight independent and involve
      regulation of SF1+ neuronal activity and sympathetic output to metabolic tissues.
      Accordingly, mice with alpha2delta-1 deletion in SF1 neurons exhibit glucose
      intolerance, altered lipolysis, and decreased cholesterol content in adipose
      tissue despite normal energy balance regulation. Profound reductions in the
      firing rate of SF1 neurons, decreased sympathetic output, and elevated
      circulating levels of serotonin are associated with these alterations. Normal
      calcium currents but reduced excitatory postsynaptic currents in mutant SF1
      neurons implicate alpha2delta-1 in the promotion of excitatory synaptogenesis
      separate from its canonical role as a calcium channel subunit. Collectively,
      these findings identify an essential mechanism that regulates VMH neuronal
      activity and glycemic and lipid control and may be a target for tackling
      metabolic disease.

PMID- 29212023
TI  - DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+
      Transfer through the MAM.
AB  - A wide range of Ca2+-mediated functions are enabled by the dynamic properties of
      Ca2+, all of which are dependent on the endoplasmic reticulum (ER) and
      mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is
      involved in the function of intracellular organelles and is linked to cognitive
      and emotional deficits. Here, we demonstrate that DISC1 localizes to the
      mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP3R1
      and downregulates its ligand binding, modulating ER-mitochondria Ca2+ transfer
      through the MAM. The disrupted regulation of Ca2+ transfer caused by DISC1
      dysfunction leads to abnormal Ca2+ accumulation in mitochondria following
      oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters
      corticosterone-induced mitochondrial Ca2+ accumulation in an oxidative stress
      dependent manner. Together, these findings link stress-associated neural stimuli
      with intracellular ER-mitochondria Ca2+ crosstalk via DISC1, providing
      mechanistic insight into how environmental risk factors can be interpreted by
      intracellular pathways under the control of genetic components in neurons.

PMID- 29212024
TI  - Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction.
AB  - Piezo2 is a mechanically activated ion channel required for touch discrimination,
      vibration detection, and proprioception. Here, we discovered that Piezo2 is
      extensively spliced, producing different Piezo2 isoforms with distinct
      properties. Sensory neurons from both mice and humans express a large repertoire
      of Piezo2 variants, whereas non-neuronal tissues express predominantly a single
      isoform. Notably, even within sensory ganglia, we demonstrate the splicing of
      Piezo2 to be cell type specific. Biophysical characterization revealed
      substantial differences in ion permeability, sensitivity to calcium modulation,
      and inactivation kinetics among Piezo2 splice variants. Together, our results
      describe, at the molecular level, a potential mechanism by which transduction is
      tuned, permitting the detection of a variety of mechanosensory stimuli.

PMID- 29212025
TI  - Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma.
AB  - We describe molecular convergence between BMI1 and CHD7 in the initiation of
      medulloblastoma. Identified in a functional genomic screen in mouse models, a
      BMI1High;CHD7Low expression signature within medulloblastoma characterizes
      patients with poor overall survival. We show that BMI1-mediated repression of the
      ERK1/2 pathway leads to increased proliferation and tumor burden in primary human
      MB cells and in a xenograft model, respectively. We provide evidence that
      repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible
      chromatin configuration in G4 MB cells with low CHD7 expression. These findings
      extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma
      pathogenesis, and they raise the possibility that pharmacological targeting of
      BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression
      levels of CHD7.

PMID- 29212026
TI  - Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis.
AB  - Angiogenesis inhibitors are important for cancer therapy, but clinically approved
      anti-angiogenic agents have shown only modest efficacy and can compromise wound
      healing. This necessitates the development of novel anti-angiogenesis therapies.
      Here, we show significantly increased EGFL6 expression in tumor versus wound or
      normal endothelial cells. Using a series of in vitro and in vivo studies with
      orthotopic and genetically engineered mouse models, we demonstrate the mechanisms
      by which EGFL6 stimulates tumor angiogenesis. In contrast to its antagonistic
      effects on tumor angiogenesis, EGFL6 blockage did not affect normal wound
      healing. These findings have significant implications for development of anti
      angiogenesis therapies.

PMID- 29212028
TI  - Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and
      Is Required for the Survival of Colon Cancer Stem Cells.
AB  - Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem
      cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid
      and serial xenotransplantation assays to functionally define the frequency of
      CSCs in a panel of patient-derived cancer organoids. These studies demonstrated
      cancer organoids to be enriched for CSCs, which varied in frequency between
      tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling
      components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase
      (ALDH)-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative
      regulator of WNT signaling in normal intestine and intestinal tumors. Here, we
      show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non
      canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule
      inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT),
      we demonstrate that non-canonical Hedgehog signaling is a positive regulator of
      WNT signaling and required for colon CSC survival.

PMID- 29212027
TI  - Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC
      Driven Evolutionary Convergence.
AB  - Diverse pathways drive resistance to BRAF/MEK inhibitors in BRAF-mutant melanoma,
      suggesting that durable control of resistance will be a challenge. By combining
      statistical modeling of genomic data from matched pre-treatment and post-relapse
      patient tumors with functional interrogation of >20 in vitro and in vivo
      resistance models, we discovered that major pathways of resistance converge to
      activate the transcription factor, c-MYC (MYC). MYC expression and pathway gene
      signatures were suppressed following drug treatment, and then rebounded during
      progression. Critically, MYC activation was necessary and sufficient for
      resistance, and suppression of MYC activity using genetic approaches or BET
      bromodomain inhibition was sufficient to resensitize cells and delay BRAFi
      resistance. Finally, MYC-driven, BRAFi-resistant cells are hypersensitive to the
      inhibition of MYC synthetic lethal partners, including SRC family and c-KIT
      tyrosine kinases, as well as glucose, glutamine, and serine metabolic pathways.
      These insights enable the design of combination therapies that select against
      resistance evolution.

PMID- 29212029
TI  - MELK Promotes Melanoma Growth by Stimulating the NF-kappaB Pathway.
AB  - Melanoma accounts for more than 80% of skin cancer-related deaths, and current
      therapies provide only short-term benefit to patients. Here, we show in melanoma
      cells that maternal embryonic leucine zipper kinase (MELK) is transcriptionally
      upregulated by the MAPK pathway via transcription factor E2F1. MELK knockdown or
      pharmacological inhibition blocked melanoma growth and enhanced the effectiveness
      of BRAFV600E inhibitor against melanoma cells. To identify mediators of MELK
      function, we performed stable isotope labeling with amino acids in cell culture
      (SILAC) and identified 469 proteins that had downregulated phosphorylation after
      MELK inhibition. Of these proteins, 139 were previously reported as substrates of
      BRAF or MEK, demonstrating that MELK is an important downstream mediator of the
      MAPK pathway. Furthermore, we show that MELK promotes melanoma growth by
      activating NF-kappaB pathway activity via Sequestosome 1 (SQSTM1/p62).
      Altogether, these results underpin an important role for MELK in melanoma growth
      downstream of the MAPK pathway.

PMID- 29212030
TI  - Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic
      Growth through Increased Angiogenesis.
AB  - Although it is well established that tumor-associated macrophages take part in
      each step of cancer progression, less is known about the distinct role of the so
      called metastasis-associated macrophages (MAMs) at the metastatic site. Previous
      studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor
      suppressive functions. However, the role of Cav1 in bone-marrow-derived cells is
      unknown. Here, we describe Cav1 as an anti-metastatic regulator in mouse models
      of lung and breast cancer pulmonary metastasis. Among all the recruited
      inflammatory cell populations, we show that MAMs uniquely express abundant levels
      of Cav1. Using clodronate depletion of macrophages, we demonstrate that
      macrophage Cav1 signaling is critical for metastasis and not for primary tumor
      growth. In particular, Cav1 inhibition does not affect MAM recruitment to the
      metastatic site but, in turn, favors angiogenesis. We describe a mechanism by
      which Cav1 in MAMs specifically restrains vascular endothelial growth factor
      A/vascular endothelial growth factor receptor 1 (VEGF-A/VEGFR1) signaling and its
      downstream effectors, matrix metallopeptidase 9 (MMP9) and colony-stimulating
      factor 1 (CSF1).

PMID- 29212031
TI  - Integration of GPCR Signaling and Sorting from Very Early Endosomes via Opposing
      APPL1 Mechanisms.
AB  - Endocytic trafficking is a critical mechanism for cells to decode complex
      signaling pathways, including those activated by G-protein-coupled receptors
      (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be
      spatially restricted between early endosomes (EEs) and the recently discovered
      endosomal compartment, the very early endosome (VEE). However, the molecular
      machinery driving GPCR activity from the VEE is unknown. Using luteinizing
      hormone receptor (LHR) as a prototype GPCR for this compartment, along with
      additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1
      in rapid recycling and endosomal cAMP signaling without impacting the EE
      localized beta2-adrenergic receptor. LHR recycling is driven by receptor-mediated
      Galphas/cAMP signaling from the VEE and PKA-dependent phosphorylation of APPL1 at
      serine 410. Receptor/Galphas endosomal signaling is localized to microdomains of
      heterogeneous VEE populations and regulated by APPL1 phosphorylation. Our study
      uncovers a highly integrated inter-endosomal communication system enabling cells
      to tightly regulate spatially encoded signaling.

PMID- 29212032
TI  - Targeting the Conserved Fusion Loop of HAP2 Inhibits the Transmission of
      Plasmodium berghei and falciparum.
AB  - Inhibiting transmission of Plasmodium is a central strategy in malarial
      eradication, and the biological process of gamete fusion during fertilization is
      a proven target for this approach. The lack of a structure or known molecular
      function of current anti-malarial vaccine targets has previously been a hindrance
      in the development of transmission-blocking vaccines. Structure/function studies
      have indicated that the conserved gamete membrane fusion protein HAP2 is a class
      II viral fusion protein. Here, we demonstrate that targeting a function-critical
      site of the fusion/cd loop with species-specific antibodies reduces Plasmodium
      berghei transmission in vivo by 58.9% and in vitro fertilization by up to 89.9%.
      A corresponding reduction in P. falciparum transmission (75.5%/36.4% reductions
      in intensity/prevalence) is observed in complimentary field studies. These
      results emphasize conserved mechanisms of fusion in Apicomplexa, while
      highlighting an approach to design future anti-malarial transmission-blocking
      vaccines.

PMID- 29212033
TI  - Enhancer SINEs Link Pol III to Pol II Transcription in Neurons.
AB  - Spatiotemporal regulation of gene expression depends on the cooperation of
      multiple mechanisms, including the functional interaction of promoters with
      distally located enhancers. Here, we show that, in cortical neurons, a subset of
      short interspersed nuclear elements (SINEs) located in the proximity of activity
      regulated genes bears features of enhancers. Enhancer SINEs (eSINEs) recruit the
      Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are
      transcribed by Pol III in response to neuronal depolarization. Characterization
      of an eSINE located in proximity to the Fos gene (FosRSINE1) indicated that the
      FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and
      mediates Fos relocation to Pol II factories, providing an unprecedented molecular
      link between Pol III and Pol II transcription. Strikingly, knockdown of the
      FosRSINE1 transcript induces defects of both cortical radial migration in vivo
      and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1
      acts as a strong enhancer of Fos expression in diverse physiological contexts.

PMID- 29212035
TI  - Comprehensive Characterization of the Complex lola Locus Reveals a Novel Role in
      the Octopaminergic Pathway via Tyramine Beta-Hydroxylase Regulation.
AB  - Longitudinals lacking (lola) is one of the most complex genes in Drosophila
      melanogaster, encoding up to 20 protein isoforms that include key transcription
      factors involved in axonal pathfinding and neural reprogramming. Most previous
      studies have employed loss-of-function alleles that disrupt lola common exons,
      making it difficult to delineate isoform-specific functions. To overcome this
      issue, we have generated isoform-specific mutants for all isoforms using
      CRISPR/Cas9. This enabled us to study specific isoforms with respect to
      previously characterized roles for Lola and to demonstrate a specific function
      for one variant in axon guidance via activation of the microtubule-associated
      factor Futsch. Importantly, we also reveal a role for a second variant in
      preventing neurodegeneration via the positive regulation of a key enzyme of the
      octopaminergic pathway. Thus, our comprehensive study expands the functional
      repertoire of Lola functions, and it adds insights into the regulatory control of
      neurotransmitter expression in vivo.

PMID- 29212034
TI  - GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress
      in Human Corneal Cells.
AB  - GADD34, a stress-induced regulatory subunit of the phosphatase PP1, is known to
      function in hyperosmotic stress through its well-known role in the integrated
      stress response (ISR) pathway. Adaptation to hyperosmotic stress is important for
      the health of corneal epithelial cells exposed to changes in extracellular
      osmolarity, with maladaptation leading to dry eye syndrome. This adaptation
      includes induction of SNAT2, an endoplasmic reticulum (ER)-Golgi-processed
      protein, which helps to reverse the stress-induced loss of cell volume and
      promote homeostasis through amino acid uptake. Here, we show that GADD34 promotes
      the processing of proteins synthesized on the ER during hyperosmotic stress
      independent of its action in the ISR. We show that GADD34/PP1 phosphatase
      activity reverses hyperosmotic-stress-induced Golgi fragmentation and is
      important for cis- to trans-Golgi trafficking of SNAT2, thereby promoting SNAT2
      plasma membrane localization and function. These results suggest that GADD34 is a
      protective molecule for ocular diseases such as dry eye syndrome.

PMID- 29212037
TI  - A Bacterial Receptor PcrK Senses the Plant Hormone Cytokinin to Promote
      Adaptation to Oxidative Stress.
AB  - Recognition of the host plant is a prerequisite for infection by pathogenic
      bacteria. However, how bacterial cells sense plant-derived stimuli, especially
      chemicals that function in regulating plant development, remains completely
      unknown. Here, we have identified a membrane-bound histidine kinase of the
      phytopathogenic bacterium Xanthomonas campestris, PcrK, as a bacterial receptor
      that specifically detects the plant cytokinin 2-isopentenyladenine (2iP). 2iP
      binds to the extracytoplasmic region of PcrK to decrease its autokinase activity.
      Through a four-step phosphorelay, 2iP stimulation decreased the phosphorylation
      level of PcrR, the cognate response regulator of PcrK, to activate the
      phosphodiesterase activity of PcrR in degrading the second messenger 3',5'-cyclic
      diguanylic acid. 2iP perception by the PcrK-PcrR remarkably improves bacterial
      tolerance to oxidative stress by regulating the transcription of 56 genes,
      including the virulence-associated TonB-dependent receptor gene ctrA. Our results
      reveal an evolutionarily conserved, inter-kingdom signaling by which
      phytopathogenic bacteria intercept a plant hormone signal to promote adaptation
      to oxidative stress.

PMID- 29212036
TI  - DeltaNp63 Inhibits Oxidative Stress-Induced Cell Death, Including Ferroptosis,
      and Cooperates with the BCL-2 Family to Promote Clonogenic Survival.
AB  - The BCL-2 family proteins are central regulators of apoptosis. However, cells
      deficient for BAX and BAK or overexpressing BCL-2 still succumb to oxidative
      stress upon DNA damage or matrix detachment. Here, we show that DeltaNp63alpha
      overexpression protects cells from oxidative stress induced by oxidants, DNA
      damage, anoikis, or ferroptosis-inducing agents. Conversely, DeltaNp63alpha
      deficiency increases oxidative stress. Mechanistically, DeltaNp63alpha
      orchestrates redox homeostasis through transcriptional control of glutathione
      biogenesis, utilization, and regeneration. Analysis of a lung squamous cell
      carcinoma dataset from The Cancer Genome Atlas (TCGA) reveals that TP63
      amplification/overexpression upregulates the glutathione metabolism pathway in
      primary human tumors. Strikingly, overexpression of DeltaNp63alpha promotes
      clonogenic survival of p53-/-Bax-/-Bak-/- cells against DNA damage. Furthermore,
      co-expression of BCL-2 and DeltaNp63alpha confers clonogenic survival against
      matrix detachment, disrupts the luminal clearance of mammary acini, and promotes
      cancer metastasis. Our findings highlight the need for a simultaneous blockade of
      apoptosis and oxidative stress to promote long-term cellular well-being.

PMID- 29212038
TI  - Co-chaperone BAG2 Determines the Pro-oncogenic Role of Cathepsin B in Triple
      Negative Breast Cancer Cells.
AB  - Triple-negative breast cancer (TNBC) is considered incurable with currently
      available treatments, highlighting the need for therapeutic targets and
      predictive biomarkers. Here, we report a unique role for Bcl-2-associated
      athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating
      the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme.
      Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis
      by increasing the intracellular mature form of cathepsin B, whereas BAG2
      expression induces metastasis by blocking the auto-cleavage processing of pro
      cathepsin B via interaction with the propeptide region. BAG2 regulates pro
      cathepsin B/annexin II complex formation and facilitates the trafficking of pro
      cathespin-B-containing TGN38-positive vesicles toward the cell periphery, leading
      to the secretion of pro-cathepsin B, which induces metastasis. Collectively, our
      results uncover BAG2 as a regulator of the oncogenic function of pro-cathepsin B
      and a potential diagnostic and therapeutic target that may reduce the burden of
      metastatic breast cancer.

PMID- 29212039
TI  - Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome
      Scale Network Modeling.
AB  - Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and
      self-renewal, yet systems-level understanding of stem cell metabolism has been
      limited by the lack of genome-scale network models. Here, we develop a systems
      approach to integrate time-course metabolomics data with a computational model of
      metabolism to analyze the metabolic state of naive and primed murine pluripotent
      stem cells. Using this approach, we find that one-carbon metabolism involving
      phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a
      key pathway that differs between the two states, resulting in differential
      sensitivity to anti-folates. The model also predicts that the pluripotency factor
      Lin28 regulates this one-carbon metabolic pathway, which we validate using
      metabolomics data from Lin28-deficient cells. Moreover, we identify and validate
      metabolic reactions related to S-adenosyl-methionine production that can
      differentially impact histone methylation in naive and primed cells. Our network
      based approach provides a framework for characterizing metabolic changes
      influencing pluripotency and cell fate.

PMID- 29212040
TI  - Molecular and Cellular Organization of Taste Neurons in Adult Drosophila Pharynx.
AB  - The Drosophila pharyngeal taste organs are poorly characterized despite their
      location at important sites for monitoring food quality. Functional analysis of
      pharyngeal neurons has been hindered by the paucity of molecular tools to
      manipulate them, as well as their relative inaccessibility for neurophysiological
      investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal
      taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression
      analysis. The organization of pharyngeal neurons reveals similarities and
      distinctions in receptor repertoires and neuronal groupings compared to external
      taste neurons. We validate the mapping results by pinpointing a single pharyngeal
      neuron required for feeding avoidance of L-canavanine. Inducible activation of
      pharyngeal taste neurons reveals functional differences between external and
      internal taste neurons and functional subdivision within pharyngeal sweet
      neurons. Our results provide roadmaps of pharyngeal taste organs in an insect
      model system for probing the role of these understudied neurons in controlling
      feeding behaviors.

PMID- 29212041
TI  - Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains.
AB  - The elicitation of autologous neutralizing responses by immunization with HIV-1
      envelope (Env) trimers conformationally stabilized in a prefusion closed state
      has generated considerable interest in the HIV-1 vaccine field. However, soluble
      prefusion closed Env trimers have been produced from only a handful of HIV-1
      strains, limiting their utility as vaccine antigens and B cell probes. Here, we
      report the engineering from 81 HIV-1 strains of soluble, fully cleaved, prefusion
      Env trimers with appropriate antigenicity. We used a 96-well expression-screening
      format to assess the ability of artificial disulfides and Ile559Pro substitution
      (DS-SOSIP) to produce soluble cleaved-Env trimers; from 180 Env strains, 20
      yielded prefusion closed trimers. We also created chimeras, by utilizing
      structure-based design to incorporate select regions from the well-behaved BG505
      strain; from 180 Env strains, 78 DS-SOSIP-stabilized chimeras, including 61
      additional strains, yielded prefusion closed trimers. Structure-based design thus
      enables the production of prefusion closed HIV-1-Env trimers from dozens of
      diverse strains.

PMID- 29212042
TI  - Facial Nerve Injury and Other Complications Following Retromandibular Subparotid
      Approach for the Management of Condylar Fractures.
AB  - PURPOSE: To estimate the prevalence and identify risk factors for facial nerve
      paralysis (FNP) and other postoperative complications after the use of the
      retromandibular subparotid approach (RMSA) for the treatment of condylar
      fractures. MATERIALS AND METHODS: Radiologic and clinical data from all patients
      who underwent an RMSA from 2007 through 2015 at the University Hospital of Geneva
      (Geneva, Switzerland) were retrospectively reviewed. The primary and secondary
      outcome variables were, respectively, FNP and other complications (unesthetic
      scars, infection, nonunion, malocclusion, salivary fistula, Frey syndrome, and
      loosening or breaking of plates and screws). Predictor variables included age,
      gender, mechanism of injury, delay from injury to surgery, surgeon's experience,
      location of fracture, side and pattern of fracture, concomitant facial fractures,
      and status of healing. Univariable logistic regression statistics were computed.
      RESULTS: Forty-eight subcondylar fractures in 43 consecutive patients were
      treated using the RMSA. Six fracture sites (12.5%) developed a temporary FNP that
      completely resolved within 4 months. Fractures at the neck level and with the
      comminution pattern were significant risk factors of postoperative FNP (P = .04
      and P < .001, respectively; odds ratio = 82). Eight patients (18.6%) developed a
      slight transient malocclusion that was completely corrected within 3 to 4 weeks
      using guiding elastics and 1 patient (2.3%) had a wound dehiscence that resolved
      with a visible but thin and linear scar. CONCLUSION: The present study showed
      that 1) the FNP rate after the RMSA to surgery for condylar fractures was similar
      to that reported after the transparotid variant; 2) the FNP was transient and
      completely resolved in all patients; 3) neck and comminuted condylar fractures
      were statistically associated with increased risk of developing a postoperative
      temporary FNP; and 4) the final outcome was favorable with no major complications
      in any of the patients.

PMID- 29212044
TI  - Multi-spectroscopic and molecular docking studies on the interaction of
      darunavir, a HIV protease inhibitor with calf thymus DNA.
AB  - Molecular interaction of darunavir (DRV), a HIV protease inhibitor with calf
      thymus deoxyribonucleic acid (ct-DNA) was studied in physiological buffer (pH7.4)
      by multi-spectroscopic approaches hand in hand with viscosity measurements and
      molecular docking technique. The UV absorption and fluorescence results together
      revealed the formation of a DRV-ct-DNA complex having binding affinities of the
      order of 103M-1, which was more in keeping with the groove binding. The results
      that DRV bound to ct-DNA via groove binding mode was further evidenced by KI
      quenching studies, viscosity measurements, competitive binding investigations
      with EB and Rhodamine B and CD spectral analysis. The effect of ionic strength
      indicated the negligible involvement of electrostatic interaction between DRV and
      ct-DNA. The thermodynamic parameters regarding the binding interaction of DRV
      with ct-DNA in terms of enthalpy change (DeltaH0) and entropy change (DeltaS0)
      were -63.19kJ mol-1 and -141.92J mol-1K-1, indicating that hydrogen bonds and van
      der Waals forces played a predominant role in the binding process. Furthermore,
      molecular simulation studies suggested that DRV molecule was prone to bind in the
      A-T rich region of the minor groove of DNA.

PMID- 29212043
TI  - Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate.
AB  - Mitochondrial membrane uncoupling protein 3 (UCP3) is not only expressed in
      skeletal muscle and heart, but also in brown adipose tissue (BAT) alongside UCP1,
      which facilitates a proton leak to support non-shivering thermogenesis. In
      contrast to UCP1, the transport function and molecular mechanism of UCP3
      regulation are poorly investigated, although it is generally agreed upon that
      UCP3, analogous to UCP1, transports protons, is activated by free fatty acids
      (FFAs) and is inhibited by purine nucleotides (PNs). Because the presence of two
      similar uncoupling proteins in BAT is surprising, we hypothesized that UCP1 and
      UCP3 are differently regulated, which may lead to differences in their functions.
      By combining atomic force microscopy and electrophysiological measurements of
      recombinant proteins reconstituted in planar bilayer membranes, we compared the
      level of protein activity with the bond lifetimes between UCPs and PNs. Our data
      revealed that, in contrast to UCP1, UCP3 can be fully inhibited by all PNs and
      IC50 increases with a decrease in PN-phosphorylation. Experiments with mutant
      proteins demonstrated that the conserved arginines in the PN-binding pocket are
      involved in the inhibition of UCP1 and UCP3 to different extents. Fatty acids
      compete with all PNs bound to UCP1, but only with ATP bound to UCP3. We
      identified phosphate as a novel inhibitor of UCP3 and UCP1, which acts
      independently of PNs. The differences in molecular mechanisms of the inhibition
      between the highly homologous transporters UCP1 and UCP3 indicate that UCP3 has
      adapted to fulfill a different role and possibly another transport function in
      BAT.

PMID- 29212045
TI  - Interactions of hemin with bovine serum albumin and human hemoglobin: A
      fluorescence quenching study.
AB  - The binding interactions between hemin (Hmi) and bovine serum albumin (BSA) or
      human hemoglobin (HHb), respectively, have been examined in aqueous solution at
      pH=7.4, applying UV-vis absorption, as well as steady-state, synchronous and
      three-dimensional fluorescence spectra techniques. Representative results
      received for both BSA and HHb intrinsic fluorescence proceeding from the
      interactions with hemin suggest the formation of stacking non-covalent and non
      fluorescent complexes in both the Hmi-BSA and Hmi-HHb systems, with highly
      possible concurrent formation of a coordinate bond between a group on the protein
      surface and the metal in Hmi molecule. All the values of calculated parameters,
      the binding, fluorescence quenching and bimolecular quenching rate constants
      point to the involvement of static quenching in both the systems studied. The
      blue shift in the synchronous fluorescence spectra imply the participation of
      both tryptophan and tyrosine residues in quenching of BSA and HHb intrinsic
      fluorescence. Depicted outcomes suggest that hemin is supposedly able to
      influence the physiological functions of BSA and HHb, the most important blood
      proteins, particularly in case of its overuse.

PMID- 29212046
TI  - Hematopoietic defects in response to reduced Arhgap21.
AB  - Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which
      function as negative regulators of Rho GTPases. Arhgap21 has been implicated in
      adhesion and migration of cancer cells. However, the role of Arhgap21 has never
      been investigated in hematopoietic cells. Herein, we evaluated functional aspects
      of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient
      (Arhgap21+/-) mouse. Our results show that Arhgap21+/- mice have an increased
      frequency of phenotypic HSC, impaired ability to form progenitor colonies in
      vitro and decreased hematopoietic engraftment in vivo, along with a decrease in
      LSK cell frequency during serial bone marrow transplantation. Arhgap21+/-
      hematopoietic progenitor cells have impaired adhesion and enhanced mobilization
      of immature LSK and myeloid progenitors. Arhgap21+/- mice also exhibit reduced
      erythroid commitment and differentiation, which was recapitulated in human
      primary cells, in which knockdown of ARHGAP21 in CMP and MEP resulted in
      decreased erythroid commitment. Finally, we observed enhanced RhoC activity in
      the bone marrow cells of Arhgap21+/- mice, indicating that Arhgap21 functions in
      hematopoiesis may be at least partially mediated by RhoC inactivation.

PMID- 29212047
TI  - Whole brain neuronal abnormalities in focal epilepsy quantified with proton MR
      spectroscopy.
AB  - OBJECTIVE: To test the hypothesis that localization-related epilepsy is
      associated with widespread neuronal dysfunction beyond the ictal focus, reflected
      by a decrease in patients' global concentration of their proton MR spectroscopy
      (1H-MRS) observed marker, N-acetyl-aspartate (NAA). METHODS: Thirteen patients
      with localization-related epilepsy (7 men, 6 women) 40+/-13 (mean+/-standard
      deviation)years old, 8.3+/-13.4years of disease duration; and 14 matched
      controls, were scanned at 3 T with MRI and whole-brain (WB) 1H MRS. Intracranial
      fractions of brain volume, gray and white matter (fBV, fGM, fWM) were segmented
      from the MRI, and global absolute NAA creatine (Cr) and choline (Cho)
      concentrations were estimated from their WB 1H MRS. These metrics were compared
      between patients and controls using an unequal variance t test. RESULTS:
      Patients' fBV, fGM and fWM: 0.81+/-0.07, 0.47+/-0.04, 0.31+/-0.04 were not
      different from controls' 0.79+/-0.05, 0.48+/-0.04, 0.32+/-0.02; nor were their Cr
      and Cho concentrations: 7.1+/-1.1 and 1.3+/-0.2 millimolar (mM) versus 7.7+/-0.7
      and 1.4+/-0.1mM (p>0.05 all). Patients' global NAA concentration: 11.5+/-1.5 mM,
      however, was 12% lower than controls' 13.0+/-0.8mM (p=0.004). CONCLUSIONS: These
      findings indicate that neuronal dysfunction in localization-related epilepsy
      extends globally, beyond the ictal zone, but without atrophy or spectroscopic
      evidence of other pathology. This suggests a diffuse decline in the neurons'
      health, rather than their number, early in the disease course. WB 1H-MRS
      assessment, therefore, may be a useful tool for quantification of global neuronal
      dysfunction load in epilepsy.

PMID- 29212048
TI  - Electroclinical features of epilepsy associated with 1p36 deletion syndrome: A
      review.
AB  - 1p36 terminal deletion is a recently recognized syndrome with multiple congenital
      anomalies and intellectual disability. It occurs approximately in 1 out of 5000
      to 10,000 live births and is the most common subtelomeric microdeletion observed
      in human. Medical problems commonly caused by terminal deletions of 1p36 include
      developmental delay, intellectual disability, seizures, vision problems, hearing
      loss, short stature, brain anomalies, congenital heart defects, cardiomyopathy,
      renal anomalies and distinctive facial features. Although the syndrome is
      considered clinically recognizable, there is significant phenotypic variation
      among affected individuals. Genotype-phenotype correlation in this syndrome is
      complicated, because of the similar clinical evidence seen in patients with
      different deletion sizes. We review 34 scientific articles from 1996 to 2016 that
      described 315 patients with 1p36 delection syndrome. The aim of this review is to
      find a correlation between size of the 1p36-deleted segments and the neurological
      clinical phenotypes with the analysis of electro-clinical patterns associated
      with chromosomal aberrations, that is a major tool in the identification of
      epilepsy susceptibility genes. Our finding suggest that developmental delay and
      early epilepsy are frequent findings in 1p36 deletion syndrome that can
      contribute to a poor clinical outcome for this reason this syndrome should be
      searched for in patients presenting with infantile spasms associated with a
      hypsarrhythmic EEG, particulary if they are combined with dismorphic features,
      severe hypotonia and developmental delay.

PMID- 29212049
TI  - Distribution, contents and health risk assessment of metal(loid)s in small-scale
      farms in the Ecuadorian Amazon: An insight into impacts of oil activities.

PMID- 29212050
TI  - Nitrogen loading affects microbes, nitrifiers and denitrifiers attached to
      submerged macrophyte in constructed wetlands.
AB  - Submerged macrophytes and biofilms are important components of wetlands. However,
      little is known about the changes of microbes in biofilms attached to submerged
      macrophytes upon nitrogen loading. This study investigated the changes of
      microbes, algae, nitrifiers and denitrifiers in biofilms attached to the leaves
      of artificial plants (AP), Potamogeton malaianus (PM), Vallisneria natans (VN)
      and Hydrilla verticillata (HV) under varied initial concentrations of total
      nitrogen (TN). Nitrogen addition increased biofilm biomass and changed dissolved
      oxygen concentrations and pH values in overlaying water. Epiphytic algal
      densities showed the same trend at the same N level:AP>PM>VN>HV. As revealed by
      cluster analysis at phylum level, algae compositions in biofilm from four plants
      showed some host-specific at 2 and 12mgL-1 TN, but was clustered in the same
      group at 22mgL-1 TN regardless of plant species. Submerged macrophytes had better
      performance in total N removal than AP. In general, N application significantly
      increased the abundance of amoA, nirK, nirS, napA and cnorB in biofilm. The
      abundance of the denitrification genes (nirK, nirS, napA, narG and cnorB) was
      positively correlated with nitrogen application, while amoA was correlated with
      concentration of dissolved oxygen. These results indicate that N loadings
      stimulated the growth of biofilms attached to submerged macrophyte and the
      removal of total N can be partially ascribed to the synergistic interactions of
      submerged macrophyte and biofilms in wetlands. These results highlight the
      ecological role of submerged macrophyte-biofilm system in nitrogen removal in
      wetlands.

PMID- 29212051
TI  - Land use and climate change impacts on runoff and soil erosion at the hillslope
      scale in the Brazilian Cerrado.
AB  - Land use and climate change can influence runoff and soil erosion, threatening
      soil and water conservation in the Cerrado biome in Brazil. The adoption of a
      process-based model was necessary due to the lack of long-term observed data. Our
      goals were to calibrate the WEPP (Water Erosion Prediction Project) model for
      different land uses under subtropical conditions in the Cerrado biome; predict
      runoff and soil erosion for these different land uses; and simulate runoff and
      soil erosion considering climate change. We performed the model calibration using
      a 5-year dataset (2012-2016) of observed runoff and soil loss in four different
      land uses (wooded Cerrado, tilled fallow without plant cover, pasture, and
      sugarcane) in experimental plots. Selected soil and management parameters were
      optimized for each land use during the WEPP model calibration with the existing
      field data. The simulations were conducted using the calibrated WEPP model
      components with a 100-year climate dataset created with CLIGEN (weather
      generator) based on regional climate statistics. We obtained downscaled General
      Circulation Model (GCM) projections, and runoff and soil loss were predicted with
      WEPP using future climate scenarios for 2030, 2060, and 2090 considering
      different Representative Concentration Pathways (RCPs). The WEPP model had an
      acceptable performance for the subtropical conditions. Land use can influence
      runoff and soil loss rates in a significant way. Potential climate changes, which
      indicate the increase of rainfall intensities and depths, may increase the
      variability and rates of runoff and soil erosion. However, projected climate
      changes did not significantly affect the runoff and soil erosion for the four
      analyzed land uses at our location. Finally, the runoff behavior was distinct for
      each land use, but for soil loss we found similarities between pasture and wooded
      Cerrado, suggesting that the soil may attain a sustainable level when the land
      management follows conservation principles.

PMID- 29212052
TI  - Biotic diversity of benthic macroinvertebrates at contrasting glacier-fed systems
      in Patagonia Mountains: The role of environmental heterogeneity facing global
      warming.
AB  - Patagonia is by far the largest glacierized area in South America. However,
      little is known about ecology, functioning and biodiversity of glacier-fed
      streams facing global warming. We investigated changes in environmental features
      and macroinvertebrate communities along a longitudinal gradient of glacier
      influence of two Patagonian systems that differ in glacier cover magnitude and
      the spatial sequence of lotic and lentic phases. Both glaciers, Torrecillas
      (~5.5km2, Torrecillas system) and Conico (~0.44km2, Baggilt system), are
      retreating. Longitudinal distribution of benthic invertebrates partially fitted
      to predictions for glacierized temperate systems, with Diamesinae spp. dominating
      at closest sites to the Conico, and Orthocladiinae increasing downstream, but
      patterns were unclear at Torrecillas. Generalized Linear Model identified
      chlorophyll a and conductivity as having significant effect on richness and
      density respectively at Torrecillas; detritus biomass and gravel influenced
      species richness, and boulder percentage and water temperature affected density,
      at Baggilt. Canonical Correspondence Analyses integrating benthic biota and
      environmental variables revealed that a higher environmental heterogeneity at
      Baggilt, related with spatial dimension (unshaded/shaded reaches, wetland
      reaches), local resources (detritus, bryophytes) and temperature, probably
      explained the unexpected high richness in benthic assemblages (67 taxa).
      Environmental conditions imposed by the lake outlet (proglacial) at Torrecillas
      resulted in a less diverse community (31 taxa). Finally our results suggest that
      these isolated, small glacier-fed streams typical of the Patagonian landscape
      appear highly vulnerable to global warming. Endemic elements could disappear at
      upper segments being replaced by other species common at rhithral environments,
      which might increase local diversity (alfa diversity) but decrease regional
      diversity (gamma diversity). From an ecosystem perspective stream functioning can
      result altered. Glacier retreating or disappearing threatens major ecosystem
      services for Patagonian inhabitants such as water supply, hydrological
      regulation, recreation and tourism.

PMID- 29212053
TI  - Contaminant back-diffusion from low-permeability layers as affected by
      groundwater velocity: A laboratory investigation by box model and image analysis.
AB  - Low-permeability lenses represent potential sources of long-term release when
      filled from contaminant solute through direct contact with dissolved plumes. The
      redistribution of contaminant from low to high permeability aquifer zones (Back
      Diffusion) was studied. Redistribution causes a long plume tail, commonly
      regarded as one of the main obstacles to effective groundwater remediation.
      Laboratory tests were performed to reproduce the redistribution process and to
      investigate the effect of pumping water on the remediation time of these
      contaminated low-permeability lenses. The test section used is representative of
      clay/silt lenses (k~1*10-10m/s/k~1*10-7m/s) in a sand aquifer (k~1*10-3m/s).
      Hence, an image analysis procedure was used to estimate the diffusive flux of
      contaminant released by these low-permeability zones. The proposed technique was
      validated performing a mass balance of a lens saturated by a known quantity of
      tracer. For each test, performed using a different groundwater velocity, the
      diffusive fluxes of contaminant released by lenses were compared and the
      remediation times of the low-permeability zones calculated. For each lens, the
      obtained remediation timeframes were used to define an analytical relation vs
      groundwater velocity and the coefficients of these relations were matched to
      grain size of the low-permeability lenses. Results show that an increase of the
      velocity field is not useful to diminish the total depletion times as the process
      mainly diffusive. This is significant when the remediation approach relies on
      pumping technology.

PMID- 29212054
TI  - Developmental and metabolic responses of zebrafish (Danio rerio) embryos and
      larvae to short-chain chlorinated paraffins (SCCPs) exposure.
AB  - Short-chain chlorinated paraffins (SCCPs) are highly toxic to aquatic organisms,
      but their toxicity is yet not well characterized. In this study, the
      developmental toxicity of SCCPs to zebrafish embryos/larvae was evaluated, and a
      metabolomics approach was adopted to explore the impact of SCCPs exposure on the
      metabolism in zebrafish embryos. Exposure to SCCPs at concentrations of 1
      200MUg/L did not produce an observable effect on the hatching rate and
      morphological deformities of zebrafish embryos/larvae. However, the survival rate
      of zebrafish larvae in SCCPs exposure groups decreased in a concentration
      dependent manner. The 13-day 50% lethal concentration (LC50) value of SCCPs was
      calculated to be 34.4MUg/L. Exposure to SCCPs induced a significant change of
      overall metabolism, even at environmentally relevant concentrations (1-5MUg/L).
      The most relevant pathways affected by SCCPs exposure were glycerophospholipid
      metabolism, fatty acid metabolism and purine metabolism. Exposure to SCCPs at
      concentrations of 1-5MUg/L had begun to accelerate the beta-oxidation of
      unsaturated fatty acids and very long chain fatty acids, and affect the
      transformation of guanine to xanthine in the pathway of purine metabolism.
      Furthermore, when the exposure concentrations of SCCPs were increased to 50
      200MUg/L, the levels of phospholipids and amino acids were significantly raised;
      whereas the levels of fatty acids, carnitines and inosine were significantly
      decreased. In view of the significant effect on metabolism, the sub-chronic and
      chronic toxicity of SCCPs to fish should be concerned.

PMID- 29212055
TI  - Indoor and outdoor air concentrations of volatile organic compounds and NO2 in
      schools of urban, industrial and rural areas in Central-Southern Spain.
AB  - Thirty two VOCs including alkanes, aromatic hydrocarbons, terpenes and carbonyl
      compounds together with NO2 were investigated in a kindergarten classroom, a
      primary classroom and the playground in 18 schools located in rural areas, an
      urban area (Ciudad Real) and an industrial area (Puertollano) in the province of
      Ciudad Real in central southern Spain. The most abundant pollutants at schools
      were the aldehydes formaldehyde and hexanal. After carbonyls, n-dodecane was the
      most abundant compound in the study areas. The NO2 concentrations were higher in
      the urban area, followed by industrial area and rural areas. For benzene, its
      concentration in the industrial area was significantly higher than in the urban
      and rural areas which reflects the magnitude of the contribution to the indoor
      air by petrochemical plant during the sampling period. Principal component
      analysis, indoor/outdoor ratios, multiple linear regressions and Spearman
      correlation coefficients were used to investigate the origin, the indoor
      pollutant determinants and to establish common sources between VOCs and NO2.
      Seven components were extracted from the application of PCA to the indoor
      measurements accounting for 77.5% of the total variance. The analysis of
      indoor/outdoor ratios and correlations demonstrated that sources in the indoor
      environment are prevailing for most of the investigated VOCs. Benzene and n
      pentane have a major relevance as outdoor sources, while aldehydes, terpenes,
      alkanes and most aromatic hydrocarbons as indoor sources. For NO2, ethylbenzene
      and toluene both indoor and outdoor sources probably contributed to the measured
      concentrations. Finally, the results reported in this paper demonstrate that
      during the measuring period there were not great differences in the indoor air
      quality of the schools of the three study areas.

PMID- 29212056
TI  - Fe3+-saturated montmorillonite effectively deactivates bacteria in wastewater.
AB  - Existing water disinfection practices often produce harmful disinfection
      byproducts. The antibacterial activity of Fe3+-saturated montmorillonite was
      investigated mechanistically using municipal wastewater effluents. Bacterial
      deactivation efficiency (bacteria viability loss) was 92+/-0.64% when a secondary
      wastewater effluent was mixed with Fe3+-saturated montmorillonite for 30min, and
      further enhanced to 97+/-0.61% after 4h. This deactivation efficiency was similar
      to that when the same effluent was UV-disinfected before it exited a wastewater
      treatment plant. Comparing to the secondary wastewater effluent, the bacteria
      deactivation efficiency was lower when the primary wastewater effluent was
      exposed to the same dose of Fe3+-saturated montmorillonite, reaching 29+/-18% at
      30min and 76+/-1.7% at 4h. Higher than 90% bacterial deactivation efficiency was
      achieved when the ratio between wastewater bacteria population and weight of Fe3+
      saturated montmorillonite was at <2*103CFU/mg. Furthermore, 99.6-99.9% of total
      coliforms, E. coli, and enterococci in a secondary wastewater effluent was
      deactivated when the water was exposed to Fe3+-saturated montmorillonite for 1h.
      Bacterial colony count results coupled with the live/dead fluorescent staining
      assay observation suggested that Fe3+-saturated montmorillonite deactivated
      bacteria in wastewater through two possible stages: electrostatic sorption of
      bacterial cells to the surfaces of Fe3+-saturated montmorillonite, followed by
      bacterial deactivation due to mineral surface-catalyzed bacterial cell membrane
      disruption by the surface sorbed Fe3+. Freeze-drying the recycled Fe3+-saturated
      montmorillonite after each usage resulted in 82+/-0.51% bacterial deactivation
      efficiency even after its fourth consecutive use. This study demonstrated the
      promising potential of Fe3+-saturated montmorillonite to be used in applications
      from small scale point-of-use drinking water treatment devices to large scale
      drinking and wastewater treatment facilities.

PMID- 29212057
TI  - Development of a chemical source apportionment decision support framework for
      lake catchment management.
AB  - Increasing pressures on natural resources has led to the adoption of water
      quality standards to protect ecological and human health. Lakes and reservoirs
      are particularly vulnerable to pressure on water quality owing to long residence
      times compared with rivers. This has raised the question of how to determine and
      to quantify the sources of priority chemicals (e.g. nutrients, persistent organic
      pollutants and metals) so that suitable measures can be taken to address failures
      to comply with regulatory standards. Contaminants enter lakes waters from a range
      of diffuse and point sources. Decision support tools and models are essential to
      assess the relative magnitudes of these sources and to estimate the impacts of
      any programmes of measures. This paper describes the development and testing of
      the Source Apportionment Geographical Information System (SAGIS) for future
      management of 763 lakes in England and Wales. The model uses readily available
      national data sets to estimate contributions of a number of key chemicals
      including nutrients (nitrogen and phosphorus), metals (copper, zinc, cadmium,
      lead, mercury and nickel) and organic chemicals (Polynuclear Aromatic
      Hydrocarbons) from multiple sector sources. Lake-specific sources are included
      (groundbait from angling and bird faeces) and hydrology associated with pumped
      inputs and abstraction. Validation data confirms the efficacy of the model to
      successfully predicted seasonal patterns of all types of contaminant
      concentrations under a number of hydrological scenarios. Such a tool has not been
      available on a national scale previously for such a wide range of chemicals and
      is currently being used to assist with future river basin planning.

PMID- 29212058
TI  - Genetic analysis and CRISPR typing of Salmonella enterica serovar Enteritidis
      from different sources revealed potential transmission from poultry and pig to
      human.
AB  - Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most
      prevalent serotypes in Salmonella isolated from poultry and the most commonly
      reported cause of human salmonellosis. In this study, we aimed to assess the
      genetic diversity of 329 S. Enteritidis strains isolated from different sources
      from 2009 to 2016 in China. Clustered regularly interspaced short palindromic
      repeat (CRISPR) typing was used to characterize these 262 chicken clinical
      isolates, 38 human isolates, 18 pig isolates, six duck isolates, three goose
      isolates and two isolates of unknown source. A total of 18 Enteritidis CRISPR
      types (ECTs) were identified, with ECT2, ECT8 and ECT4 as the top three ECTs.
      CRISPR typing identified ECT2 as the most prevalent ECT, which accounted for 41%
      of S. Enteritidis strains from all the sources except duck. ECT9 and ECT13 were
      identified in both pig and human isolates and revealed potential transmission
      from pig to human. A cluster analysis distributed 18 ECTs, including the top
      three ECTs, into four lineages with LI as the predominant lineage. Forty-eight
      out of 329 isolates were subjected to whole genome sequence typing, which divided
      them into four clusters, with Cluster I as the predominant cluster. Cluster I
      included 92% (34/37) of strains located in LI identified from the CRISPR typing,
      confirming the good correspondence between both typing methods. In addition, the
      CRISPR typing also revealed the close relationship between ECTs and isolated
      areas, confirming that CRISPR spacers might be obtained by bacteria from the
      unique phage or plasmid pools in the environment. However, further analysis is
      needed to determine the function of CRISPR-Cas systems in Salmonella and the
      relationship between spacers and the environment.

PMID- 29212059
TI  - On the nature of solvatochromic effect: The riboflavin absorption spectrum as a
      case study.
AB  - We present here the calculation of the absorption spectrum of riboflavin in
      acetonitrile and dimethyl sulfoxide using a hybrid quantum/classical approach,
      namely the perturbed matrix method, based on quantum mechanical calculations and
      molecular dynamics simulations. The calculated spectra are compared to the
      absorption spectrum of riboflavin previously calculated in water and to the
      experimental spectra obtained in all three solvents. The experimentally observed
      variations in the absorption spectra upon change of the solvent environment are
      well reproduced by the calculated spectra. In addition, the nature of the excited
      states of riboflavin interacting with different solvents is investigated, showing
      that environment effects determine a recombination of the gas-phase electronic
      states and that such a recombination is strongly affected by the polarity of the
      solvent inducing significant changes in the absorption spectra.

PMID- 29212060
TI  - Compound Interest: Assessing the Effects of Chemical Mixtures in Vivo.

PMID- 29212062
TI  - Mix Masters: Using a New Tool to Identify Commonly Occurring Chemical Mixtures.

PMID- 29212061
TI  - Ambient Ozone Pollution and Daily Mortality: A Nationwide Study in 272 Chinese
      Cities.
AB  - BACKGROUND: Few large multicity studies have been conducted in developing
      countries to address the acute health effects of atmospheric ozone pollution.
      OBJECTIVE: We explored the associations between ozone and daily cause-specific
      mortality in China. METHODS: We performed a nationwide time-series analysis in
      272 representative Chinese cities between 2013 and 2015. We used distributed lag
      models and over-dispersed generalized linear models to estimate the cumulative
      effects of ozone (lagged over 0-3 d) on mortality in each city, and we used
      hierarchical Bayesian models to combine the city-specific estimates. Regional,
      seasonal, and demographic heterogeneity were evaluated by meta-regression.
      RESULTS: At the national-average level, a 10-MUg/m3 increase in 8-h maximum ozone
      concentration was associated with 0.24% [95% posterior interval (PI): 0.13%,
      0.35%], 0.27% (95% PI: 0.10%, 0.44%), 0.60% (95% PI: 0.08%, 1.11%), 0.24% (95%
      PI: 0.02%, 0.46%), and 0.29% (95% PI: 0.07%, 0.50%) higher daily mortality from
      all nonaccidental causes, cardiovascular diseases, hypertension, coronary
      diseases, and stroke, respectively. Associations between ozone and daily
      mortality due to respiratory and chronic obstructive pulmonary disease
      specifically were positive but imprecise and nonsignificant. There were no
      statistically significant differences in associations between ozone and
      nonaccidental mortality according to region, season, age, sex, or educational
      attainment. CONCLUSIONS: Our findings provide robust evidence of higher
      nonaccidental and cardiovascular mortality in association with short-term
      exposure to ambient ozone in China. https://doi.org/10.1289/EHP1849.

PMID- 29212063
TI  - Erratum: Associations between Ambient Fine Particulate Oxidative Potential and
      Cardiorespiratory Emergency Department Visits.
AB  - [This corrects the article DOI: 10.1289/EHP1545.].

PMID- 29212064
TI  - MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous
      Thromboembolism: A Retrospective Chart Review Study.
AB  - BACKGROUND: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme in
      homocysteine metabolism. This study aims to determine the impact of MTHFR
      polymorphisms on plasma homocysteine levels and risks of venous thromboembolism
      (VTE). METHODS: This retrospective chart review study included a total of 188
      subjects who were tested for MTHFR polymorphisms at Metrowest Coagulation
      Laboratory between April 2011 and April 2016. Two independent coders were trained
      to extract relevant clinical data for statistical analysis. RESULTS: VTE occurred
      in 50% of patients with compound mutation, compared with only 28.6% of subjects
      from the wild-type group. Patients with heterozygous or homozygous A1298C or
      C677T variants had an intermediate risk of VTE. The median homocysteine level in
      the wild-type group was slightly lower than that of heterozygous or homozygous
      MTHFR variants. The difference, however, was not significant (p = 0.6193).
      Moreover, there was no difference in plasma homocysteine level between patients
      with VTE versus VTE-free (p = 0.4923). CONCLUSIONS: Heterozygous or homozygous
      MTHFR variants, especially a compound mutation, are associated with increased
      risk of VTE. Hyperhomocysteinemia does not correlate with MTHFR polymorphisms or
      VTE risk. Hence, MTHFR genotyping provides more consistent assessment of VTE
      risk. This information can be incorporated into risk stratification for early
      intervention and prophylaxis of VTE.

PMID- 29212065
TI  - Development of the Visual System in a Burrow-Nesting Seabird: Leach's Storm
      Petrel.
AB  - Little is known about the development of vision in wild birds. It is unknown, for
      example, whether the ability to see can be predicted by the level of prenatal
      growth or whether the eyes are open at hatching in a particular species. In this
      study, we investigated the growth of eyes, the formation of retinal ganglion cell
      topography, and the appearance of simple, visually guided behaviours in chicks of
      a small procellariiform seabird, Leach's storm petrel (Oceanodroma leucorhoa).
      This semi-precocial species, which has a well-developed sense of smell, nests in
      underground burrows where adults provision chicks for 6-8 weeks in the dark
      before fledging. Retinal ganglion cell topographic maps revealed that fine-tuning
      of cell distribution does not happen early in development, but rather that the
      ganglion cell layer continues to mature throughout provisioning and probably even
      after fledging. While the olfactory bulbs reached adult size around 7 weeks after
      hatching, the eyes and telencephalon continued to grow. Optokinetic head response
      and artificial burrow finding experiments indicated that chicks in the 2nd week
      after hatching lack even the most basic visually guided behaviours and are
      probably blind. Thus, vision in Leach's storm petrel chicks starts to function
      sometime around the 3rd week after hatching, well after the eyes have opened and
      the olfactory system is functional.

PMID- 29212066
TI  - Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway.
AB  - BACKGROUND: Gliomas result in the highest morbidity and mortality rates of
      intracranial primary central nervous system tumors because of their aggressive
      growth characteristics and high postoperative recurrence. They are characterized
      by genetic instability, intratumoral histopathological variability and
      unpredictable clinical behavior in patients. Proliferation is a key aspect of the
      clinical progression of malignant gliomas, complicating complete surgical
      resection and enabling tumor regrowth and further proliferation of the surviving
      tumor cells. METHODS: The expression of Fstl1 was detected by western blotting
      and qRT-PCR. We used cell proliferation and colony formation assays to measure
      proliferation. Then, flow cytometry was used to analyze cell cycle progression.
      The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated
      using immunohistochemical staining. Furthermore, we used coimmunoprecipitation
      (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4
      and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of
      tumors in vivo. RESULTS: We found that follistatin-like 1 (Fstl1) was upregulated
      in high-grade glioma specimens and that its levels correlated with poor
      prognosis. Fstl1 upregulation increased cell proliferation, colony formation and
      cell cycle progression, while its knockdown inhibited these processes. Moreover,
      Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor
      (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1
      overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway,
      while BMP4 overexpression reversed this effect. CONCLUSION: Our study
      demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8
      signaling pathway, and these findings suggest potential new glioblastoma
      treatment strategies.

PMID- 29212068
TI  - Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial
      Nitric Oxide Synthase Stimulation in Rats.
AB  - BACKGROUND/AIMS: L-arginine is an important mediator of cell division, wound
      healing, and immune function. It can be transformed by the nitric oxide synthase
      (NOS) to nitric oxide (NO), an important cell signaling molecule. Recent studies
      from our laboratory demonstrate specific effects of L-arginine (10mM) exposure on
      gastric acid secretion in rat parietal cells. METHODS: Studies were performed
      with isolated gastric glands and the pH sensitive dye BCECF-AM +/- L-arginine to
      examine its effects on acid secretion. The direct NO-donor diethylamine NONOate
      sodium salt hydrate, was also used while monitoring intracellular pH. The
      specific inhibitor of the intracellular NO signal cascade ODQ was also used.
      RESULTS: We found that gastric proton extrusion was activated with application of
      L-arginine (10mM), in a separate series when L-arginine (10mM) + L-NAME (30uM)
      were added there was no acid secretion. Addition of the NO-donor diethylamine
      NONOate sodium salt hydrate (10uM) also induced acid secretion. When the
      selective sGC-inhibitor ODQ was added with NONOate we did not observe acid
      secretion. CONCLUSION: We conclude that L-arginine is a novel secretagogue, which
      can mediate gastric acid secretion. Furthermore, the intake of L-arginine causes
      direct activation of the H+, K+ ATPase and increased proton extrusion from
      parietal cells resulting in the increased risk for acid-related diseases. The
      NO/sGC/cGMP pathway has never been described as a possible intracellular
      mechanism for H+, K+ ATPase activation before and presents a completely new
      scientific finding. Moreover, our studies demonstrate a novel role for L-NAME to
      effectively eliminate NOS induced acid secretion and thereby reducing the risk
      for L-arginine inducible ulcer disease.

PMID- 29212067
TI  - Lenalidomide Maintenance after R-CHOP Therapy in Diffuse Large B-Cell Lymphoma:
      Can It Be a Standard of Care.
AB  - Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma subtype which
      requires immediate treatment. Standard treatment is usually a combined immune
      chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisone (R-CHOP). Since R-CHOP was approved, several attempts to combine it
      with novel agents and/or use them as maintenance therapy failed to improve the
      outcome. Recently, maintenance with lenalidomide after standard immune
      chemotherapy showed promising results. This review discusses the most pertinent
      published and running studies, analyzing study design, results, and practicality.

PMID- 29212069
TI  - Cellular Effects of the Antiepileptic Drug Valproic Acid in Glioblastoma.
AB  - BACKGROUND/AIMS: Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug
      is used to treat epileptic seizure of glioblastoma patients. Besides its
      antiepileptic activity, VPA has been attributed further functions that improve
      the clinical outcome of glioblastoma patients. Those comprise the inhibition of
      some histone deacetylase (HDAC) isoforms which reportedly may result in
      radiosensitization. Retrospective analysis of patient data, however, could not
      unequivocally confirm a prolonged survival of glioblastoma patients receiving
      VPA. The present study aimed to identify potential VPA targets at the cellular
      level. METHODS: To this end, the effect of VPA on metabolism, Ca2+-, biochemical
      and electro-signaling, cell-cycling, clonogenic survival and transfilter
      migration was analyzed in three human glioblastoma lines (T98G, U-87MG, U251) by
      MTT assay, Ca2+ imaging, immunoblotting, patch-clamp recording, flow cytometry,
      delayed plating colony formation and modified Boyden chamber assays,
      respectively. In addition, the effect of VPA on clonogenic survival of primary
      glioblastoma spheroid cultures treated with temozolomide and fractionated
      radiation was assessed by limited dilution assay. RESULTS: In 2 of 3 glioblastoma
      lines, clinical relevant concentrations of VPA slightly slowed down cell cycle
      progression and decreased clonogenic survival. Furthermore, VPA induced Ca2+
      signaling which was accompanied by pronounced K+ channel activity and transfilter
      cell migration. VPA did not affect metabolic NAD(P)H formation or radioresistance
      of the glioblastoma lines. Finally, VPA did not impair clonogenic survival or
      radioresistance of temozolomide-treated primary spheroid cultures. CONCLUSIONS:
      Combined, our in vitro data do not propose a general use of VPA as a
      radiosensitizer in anti-glioblastoma therapy.

PMID- 29212071
TI  - Palmar Telangiectasias: A Cutaneous Sign for Smoking.
AB  - BACKGROUND: Telangiectasias are permanent dilations of blood capillaries which
      appear in a variety of medical conditions. Cutaneous palmar telangiectasias have
      been postulated to be associated with smoking. OBJECTIVE: To determine whether a
      significant correlation exists between palmar telangiectasias and smoking habits.
      PATIENTS AND METHODS: A total of 124 volunteers participated in this
      observational study by allowing physical evaluation of their palms and by
      completing a questionnaire. RESULTS: Palmar telangiectasias were found to be
      associated with current or past smoking. Neither age nor gender was found to be a
      co-contributor. DISCUSSION: Palmar telangiectasias were found to constitute
      highly specific and sensitive markers for prolonged smoking.

PMID- 29212072
TI  - Expression of TNFalpha Receptors on Immunocompetent Cells Is Increased in Atopic
      Dermatitis.
AB  - BACKGROUND: Expression levels of cytokine and growth factor receptors have been
      found to be important in the regulation of their action. Tumor necrosis factor
      alpha (TNFalpha) is actively involved in inflammation processes in atopic
      dermatitis (AD), but the role of TNFalpha membrane receptors (TNFR) and their
      regulatory function in AD remains unclear. AIM: We aimed to determine the
      associations of parameters of TNFRalpha expression on immunocompetent cells with
      disease severity before and after therapy in AD patients. METHODS: TNFRalpha
      expression on T cells, B cells, and monocytes was evaluated by flow cytometry. To
      determine receptor numbers on the cells, Quantibrite PE beads were used. The
      content of soluble mediators was evaluated by ELISA. To reveal linear
      relationships between the index scoring AD (SCORAD) and the studied parameters,
      multiple linear regression model building was used. RESULTS: TNFR1 and TNFR2
      expression in lymphocyte and monocyte populations of AD patients was higher than
      in healthy individuals (HI). At the same time an increased percentage of positive
      cells was not associated with high receptor density, and vice versa. Serum
      content of TNFalpha, both soluble receptors, the number of TNFR2/T cells, and the
      percentage of TNFR2+ monocytes were found to be strongly associated with the
      SCORAD index. CONCLUSION: AD patients had increased TNFR expression on immune
      cells. Changes in the parameters of TNFRalpha expression compared to HI were
      associated with the disease severity index SCORAD.

PMID- 29212070
TI  - Aging and Decision-Making: A Conceptual Framework for Future Research - A Mini
      Review.
AB  - Age differences in decision-making are of theoretical interest and have important
      practical implications, but relevant lines of work are distributed across
      multiple disciplines and often lack integration. The present review proposes an
      overarching conceptual framework with the aim of connecting disjointed aspects of
      this field of research. The framework builds on process models of decision-making
      and specifies potential mechanisms behind age effects as well as relevant
      moderators including task characteristics and contextual factors. After
      summarizing the extant literature for each aspect of the framework, compensatory
      mechanisms and ecological fit between different components of the model are
      considered. Implications for real-life decision-making, remaining research gaps,
      and directions for future research are discussed.

PMID- 29212073
TI  - Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review.
AB  - Aging is a time-related process of functional decline at organelle, cellular,
      tissue, and organismal level that ultimately limits life. Cellular senescence is
      a state of permanent growth arrest in response to stress and one of the major
      drivers of aging and age-related disorders. Senescent cells accumulate with age,
      and removal of these cells delays age-related disorders in different tissues and
      prolongs healthy lifespan. One of the most studied aging mechanisms is the
      accumulation of reactive oxygen species damage in cells, organs, and organisms
      over time. Elevated oxidative stress is also found in metabolic diseases such as
      obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of
      the energy homeostasis is also associated with aging, and many age-related genes
      also control energy metabolism, with the adipose organ, comprising white, brite,
      and brown adipocytes, as an important metabolic player in the regulation of whole
      body energy homeostasis. This review summarizes transformations in the adipose
      organ upon aging and cellular senescence and sheds light on the reallocation of
      fat mass between adipose depots, on the metabolism of white and brown adipose
      tissue, on the regenerative potential and adipogenic differentiation capacity of
      preadipocytes, and on alterations in mitochondria and bioenergetics. In
      conclusion, the aging process is a lifelong, creeping process with gradual
      decline in (pre-)adipocyte function over time. Thus, slowing down the
      accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent
      preadipocytes as well as blocking deleterious compounds of the senescent
      secretome are protective measures to maintain a lasting state of health at old
      age.

PMID- 29212074
TI  - Late-Onset Alopecia Areata: A Retrospective Cohort Study.
AB  - BACKGROUND: Alopecia areata is an immune-mediated disease presenting with sudden
      onset of nonscarring hair loss. Onset is more common earlier in life, and little
      is known regarding late-onset alopecia areata. OBJECTIVES: To describe the
      epidemiology, clinical patterns, disease course, and outcome of late-onset
      alopecia areata in Israeli patients referred to a tertiary medical center.
      MATERIALS AND METHODS: This retrospective cohort study considered patients whose
      disease onset occurred at age >=50 years. Patients were recruited from among all
      alopecia areata patients visiting a tertiary center between January 2009 and
      April 2015. RESULTS: Of the 29 people included, 25 (86.2%) were female (female-to
      male ratio, 6.2:1). There was a family history of alopecia areata in 17.2%,
      thyroid disease in 31%, atopic background in 6.9%, and 17/29 (58.6%) reported a
      significant stressful event. The most common disease pattern was patchy, and
      disease was mild in the majority of participants. Complete hair regrowth was
      observed in 82.8% of participants, and 37.9% relapsed. CONCLUSION: Late-onset
      alopecia areata is characterized by marked female predominance, less extensive
      disease, and a high incidence of complete hair regrowth.

PMID- 29212075
TI  - Echinochrome A Release by Red Spherule Cells Is an Iron-Withholding Strategy of
      Sea Urchin Innate Immunity.
AB  - Cellular immune defences in sea urchins are shared amongst the coelomocytes - a
      heterogeneous population of cells residing in the coelomic fluid (blood
      equivalent) and tissues. The most iconic coelomocyte morphotype is the red
      spherule cell (or amebocyte), so named due to the abundance of cytoplasmic
      vesicles containing the naphthoquinone pigment echinochrome A. Despite their
      identification over a century ago, and evidence of antiseptic properties, little
      progress has been made in characterising the immunocompetence of these cells.
      Upon exposure of red spherule cells from sea urchins, i.e., Paracentrotus lividus
      and Psammechinus miliaris, to microbial ligands, intact microbes, and damage
      signals, we observed cellular degranulation and increased detection of cell-free
      echinochrome in the coelomic fluid ex vivo. Treatment of the cells with
      ionomycin, a calcium-specific ionophore, confirmed that an increase in
      intracellular levels of Ca2+ is a trigger of echinochrome release. Incubating
      Gram-positive/negative bacteria as well as yeast with lysates of red spherule
      cells led to significant reductions in colony-forming units. Such antimicrobial
      properties were counteracted by the addition of ferric iron (Fe3+), suggesting
      that echinochrome acts as a primitive iron chelator in echinoid biological
      defences.

PMID- 29212076
TI  - Resistance-Associated Mutations and Polymorphisms among Integrase Inhibitor-Naive
      HIV-1 Patients in Kuwait.
AB  - OBJECTIVES: Resistance-associated mutations (RAMs) in the integrase of different
      HIV-1 subtypes were investigated in a cohort of patients never exposed to
      integrase strand transfer inhibitors (INSTIs). METHODS: The viral RNA was
      extracted from plasma samples of 53 INSTI-naive patients, and the integrase
      genetic region was sequenced and analyzed for subtype assignment and drug
      resistance. RESULTS: The median viral load at sampling was 5.28 * 104 RNA
      copies/mL. Bayesian phylogenetic analysis showed 85% of the HIV-1 isolates were
      non-B subtypes, with a predominance of subtypes C (22.6%) and CRF01_AE (26.4%). A
      total of 52 and 110 mutations were found in the integrase region of HIV-1 B and
      non-B subtypes, respectively. Nonpolymorphic INSTI-RAMs were not detected in this
      study. However, the accessory mutation E157Q was found in 1 patient with
      CRF02_AG, and the polymorphic mutations L74M/I that may contribute to a reduced
      susceptibility to INSTIs in the presence of major mutations were observed in 6
      (13.3%) patients with non-B subtypes and 1 (12.5%) patient with the B subtype.
      Polymorphic mutations at positions known to harbor primary and accessory RAMs
      were also detected in this study. CONCLUSION: Our results highlight the
      importance of monitoring the emergence of INSTI-RAMS before and after the
      initiation of INSTI-based therapy.

PMID- 29212077
TI  - Long-Term Skeletal Disproportion in Childhood-Onset Crohn's Disease.
AB  - BACKGROUND: It is unclear whether Crohn's disease (CD) is associated with
      skeletal disproportion in adulthood. METHODS: Height (Ht), sitting height (SHt)
      and leg length were studied in 44 children (male: 22), 23 adults (male: 10) with
      childhood-onset (CO) CD and 26 adults (male: 9) with adult-onset (AO) CD with a
      median (range) age of 13.7 (10, 17.3), 21.5 (18, 32) and 31.0 (22, 40) years,
      respectively. RESULTS: Adults with CO-CD had a median Ht standard deviation score
      (SDS) of -0.9 (-2.3, 0.0) compared to 0.6 (-0.8, 1.0) in those with AO-CD (p <
      0.05). Compared to a normal population, men, but not women, with CO-CD also had
      lower median SHt SDS at -1.1 (2.5, -0.5) (p < 0.05). The expected positive
      association that is normally found between leg length and SHt SDS was not evident
      in the adults with CO-CD. CONCLUSION: Short stature in adults with CO-CD is more
      pronounced in men and may be associated with poor spinal growth.

PMID- 29212078
TI  - The Mechanism and Representation of Korean Three-Way Phonation Contrast: External
      Photoglottography, Intra-Oral Air Pressure, Airflow, and Acoustic Data.
AB  - This paper aims to refine our understanding of the speech mechanism and laryngeal
      features involved in the Korean lenis (/p t k/), aspirated (/ph th kh/), and
      fortis (/p' t' k'/) plosives. For this purpose we made measurements using a new
      noninvasive technique called external lighting and sensing photoglottography
      (ePGG) as well as intra-oral air pressure (Pio) above the glottis, airflow, and
      acoustic data. From simultaneous recordings of the experimental data, we were
      ableto quantify the laryngeal-oral coordination of glottal opening and a
      consonant release, and the covariance of airflow peak and duration of aspiration
      with glottal opening. The phasing of glottal opening and the 3-way phonation
      contrast occurs in the order, from early to late, fortis, lenis < aspirated
      plosives, and the glottal opening peak ranges from low to high in the same order.
      We also found that a Pio peak, the durations of a high Pio plateau and an oral
      closure, and F0 are independent of the glottal opening mechanism, varying in the
      order lenis < aspirated and fortis plosives. From these findings, we propose that
      the 2 independent patterns are accounted for by the articulator-based features
      [+/-spread glottis] and [+/-tense], respectively.

PMID- 29212079
TI  - Plasma ET-1 Concentrations Are Elevated in Pregnant Women with Hypertension -Meta
      Analysis of Clinical Studies.
AB  - BACKGROUND/AIMS: The ET system might be involved in the pathogenesis of
      hypertensive disorders during pregnancy. The objective is to analyse the impact
      of ET-1 in hypertensive pregnant women by a strict meta-analysis of published
      human clinical studies. METHODS: Based on the principle of Cochrane systematic
      reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological
      Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1)
      in the pathophysiology of gestational hypertension and preeclampsia were
      screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical
      analysis. Mean difference and 95% confidence interval (CI) were shown in inverse
      variance (IV) fixed-effects model or IV random-effects model. RESULTS: Sixteen
      published cohort studies including 1739 hypertensive cases and 409 controls were
      used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive
      pregnant women as compared to the controls (mean difference between groups: 19.02
      [15.60~22.44], P < 0.00001,). These finding were driven by severity of
      hypertension and/or degree of proteinuria. CONCLUSION: Plasma ET-1 concentrations
      are elevated in hypertensive disorders during human pregnancy. In particular
      women with preeclampsia (hypertensive pregnant women with proteinuria) have
      substantially elevated plasma ET-1 concentration as compared to pregnant women
      with normal blood pressure.

PMID- 29212080
TI  - Clinical Evaluation of Continuous Renal Replacement Therapy in Combination with
      Ultrasound-Guided Percutaneous Transhepatic Gallbladder Drainage for Acute Severe
      Biliary Pancreatitis: a Retrospective Study.
AB  - BACKGROUND/AIMS: This study aimed to report the clinical efficacy of continuous
      renal replacement therapy (CRRT) in combination with ultrasound-guided
      percutaneous transhepatic gallbladder drainage (PTGD) (CRRT+PTGD) in the
      treatment of acute severe biliary pancreatitis (ASBP). METHODS: Between January
      2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT
      (CRRT group) and 40 of those who received CRRT+PTGD (CRRT+PTGD group) at the
      Affiliated Hospital of Qingdao University (Qingdao, China) were retrospectively
      reviewed. Clinical (including abdominal pain remission time, gastrointestinal
      decompression time, Intensive Care Unit (ICU) hospital stay, respirator treatment
      time, and mortality rate), laboratory (white blood cells [WBC], platelet [PLT],
      procalcitonin [PCT], C-reactive protein [CRP], total bilirubin [TBIL], alanine
      aminotransferase [ALT], albumin [ALB], and blood lactic acid [Lac]) parameters,
      various critical disease scores, and incidence of complications after the
      treatment were compared between the two groups. RESULTS: Compared with those in
      the routine CRRT group, patients in the CRRT+PTGD group exhibited significant
      remission of clinical symptoms (i.e. shorter abdominal pain remission time,
      gastrointestinal decompression time, respirator treatment time and ICU hospital
      stay) (all P<0.05), change of laboratory parameters (WBC, PLT, PCT, CRP, TBIL,
      ALT) (P<0.05), and improvement of various critical disease scores (P<0.05).
      Moreover, the variation of most of the above parameters after versus before the
      treatment was greater in the CRRT+PTGD group than in the CRRT group (all P<0.05).
      CONCLUSION: CRRT in combination with PTGD is more effective in the treatment of
      ASBP than CRRT alone.

PMID- 29212081
TI  - In Patients with Chronic Kidney Disease Short Term Blood Pressure Variability is
      Associated with the Presence and Severity of Sleep Disorders.
AB  - BACKGROUND/AIMS: In chronic kidney disease (CKD) patients blood pressure
      variability (BPV) is associated with poor outcome. Sleep disturbances alter BP
      profiles in hypertensives but their influence on BPV in CKD patients is unknown.
      We screened a cohort of CKD/ESRD patients to investigate whether sleep quality
      impacts on BPV. METHODS: Consecutive CKD patients' sleep quality was assessed
      using validated questionnaires (Epworth Sleepiness Scale-ESS); International
      Restless legs scale-IRLS; Functional Outcomes of Sleep Questionnaire-FOSQ:
      Insomnia Severity Index-ISI; STOP-Bang). All patients underwent ambulatory blood
      pressure measurement. RESULTS: 104 out of 143 enrolled patients (78.32% stage-3
      CKD; 10.49% Stage-4; 11.19% Stage-5; 6.99% ESRD-under dialysis) completed all the
      questionnaires. 95.8% were hypertensives, 70% were non-dippers and 27.8% had
      resistant hypertension. STOP-Bang>4 proved sleep disorders in 84.84% of patients.
      Patients with IRLS>10 had greater diastolic nocturnal standard deviation (DNSD)
      and a trend (p=0.05) for systolic nocturnal SD (SNSD). Patients with ISI>14 had
      greater SNSD and in 28.8% FOSQ showed severely impaired sleep quality. Their
      systolic nocturnal BPV was significantly greater. ISI was independently
      associated with SNSD. FOSQ and diastolic nocturnal BPV were negatively correlated
      at the bivariate analysis and FOSQ independently predicts systolic nocturnal BPV
      at multivariate regression analysis. CONCLUSIONS: In CKD patients impaired sleep
      quality increases BPV, might contribute to their disease progression and worsen
      prognosis. Searching for sleep problems in CKD patients could help planning their
      treatment of sleep problems contributing to CV risk reduction. Our data provide
      the rationale working hypothesis for the need of studies with larger number of
      patients aimed to demonstrate improved outcome of CKD progression and CV risk
      with the treatment also of sleep disorders.

PMID- 29212082
TI  - Risk Factors for Chemotherapy-Related Toxicity and Adverse Events in Elderly Thai
      Cancer Patients: A Prospective Study.
AB  - OBJECTIVES: To assess factors predisposing to severe chemotherapy-related
      toxicity and adverse events (AEs) and dose modification in aging cancer patients.
      METHODS: Cancer patients aged >=70 years scheduled to receive the first cycle of
      a new chemotherapy regimen were enrolled. On the day of starting chemotherapy,
      demographic data, performance status (PS), and geriatric parameters were
      recorded. AEs and chemotherapy modification were recorded. Quality of life (QOL)
      was assessed at baseline and 3 months after starting chemotherapy or at the end
      of chemotherapy. RESULTS: We included 151 patients (mean age, 76.4 years) with
      gastrointestinal (47%), lung (24%), breast (9%), or genitourinary (6%) cancer.
      All-grade and severe AEs occurred in 83 and 42% of patients, respectively; 51.6%
      of patients required chemotherapy modification due to toxicities. A higher
      incidence of severe AEs (71% vs. 39%, p = 0.01) and poorer QOL was found in
      patients with PS 2 than in those with PS 0-1. Patients with PS 2 or who received
      palliative-intent chemotherapy or had multiple comorbidities were more likely to
      discontinue chemotherapy because of toxicity. CONCLUSIONS: PS remains a key
      predictor of chemotherapy-related toxicity in elderly patients. PS 2 was
      correlated with higher incidence of severe AEs, premature treatment
      discontinuation, and worsening QOL after treatment.

PMID- 29212083
TI  - Which Nebulizer Position Should Be Avoided? An Extended Study of Aerosol Delivery
      and Ventilator Performance during Noninvasive Positive Pressure Ventilation.
AB  - BACKGROUND: Research on the effect of nebulizer location on aerosol delivery
      during noninvasive ventilation has reached inconsistent conclusions. OBJECTIVE:
      To investigate the effects of nebulizer position on aerosol delivery efficiency
      and ventilator performance during noninvasive ventilation. METHODS: The Active
      Servo Lung 5000 respiratory simulation system (ASL5000) was used to simulate a
      COPD patient. The noninvasive ventilator was set to the spontaneous breathing
      mode. Six nebulizer positions, 2 exhalation valve types (single-arch exhalation
      port and whisper swivel), 4 combinations of inspiratory and expiratory pressure,
      and 2 respiratory rates were used. RESULTS: Significant differences between
      nebulizer positions existed in aerosol delivery (p < 0.05). Aerosol delivery
      efficiency was lower for nebulizer locations on either side of the exhalation
      valve and next to the ventilator outlet. When the nebulizer was located between
      the exhalation valve and the simulated lung, increased inspiratory pressure
      increased and increased expiratory pressure decreased delivery efficiency (both p
      < 0.05). When the nebulization device was located between the exhalation valve
      and the ventilator, no obvious trend was observed. Compared to baseline,
      nebulization lowered the air leakage volume displayed on the ventilator. There
      were no differences in ventilator performance between different nebulizer
      positions. CONCLUSIONS: The closer the nebulizer was to the exhalation valves or
      ventilator, the lower the aerosol delivery efficiency. Nebulizer position had
      little clinically significant effect on ventilator performance.

PMID- 29212084
TI  - Perioperative Outcomes and Early Survival in Octogenarians Who Underwent Radical
      Cystectomy for Bladder Cancer.
AB  - OBJECTIVE: To evaluate perioperative outcomes and early survival in a series of
      octogenarians who underwent radical cystectomy (RC) and urinary diversion for
      bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated the clinical
      records of 44 patients aged >=80 years who underwent open RC and urinary
      diversion at 2 high-volume centers between July 2013 and December 2015. Estimated
      blood loss (EBL), transfusion rate, and length of hospital stay (LOS) were
      evaluated. Ninety-day postoperative complications were stratified according to
      the type of urinary diversion. Univariable analysis was performed to identify
      predictors of overall and major complications. Overall survival (OS) was
      estimated using the Kaplan-Meier method. RESULTS: Median age was 83 years
      (interquartile range [IQR] 81-85). Age-adjusted Charlson score was >=4 in 37
      (84%) patients, and American Society of Anesthesiologists score was >=3 in 34
      (77%) patients. Ileal conduit (IC) was performed in 21/44 (48%) cases, cutaneous
      ureterostomy (CU) in 20/44 (45%), and no urinary diversion was required for 3
      (7%) dialytic patients. Median EBL was 700 mL (IQR 500-1,000) and 23 (52%)
      patients required blood transfusion. Median LOS was 13 days (IQR 10-18). Overall
      complications were recorded in 29 (66%) patients, with major complications
      observed in 12 (27%), with death occurring in 1. No differences in complications
      were observed between IC and CU. The 2-year OS estimate was 62.5%. CONCLUSIONS:
      Open RC in octogenarians has an acceptable rate of major complications and
      mortality. IC should be considered a good urinary diversion in these patients.

PMID- 29212085
TI  - The Impact of Anti-TNF Therapy on CD4+ and CD8+ Cell Subsets in Ankylosing
      Spondylitis.
AB  - OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive immune-mediated
      inflammatory disease, driven primarily by Th1 and Th17 cells. Anti-TNF therapies
      are successfully used in AS to achieve and maintain remission. However, their
      influence on the composition of T-cell subsets is not clear. We aimed to
      characterize the changes in the T-cell repertoire after a long-term anti-TNF
      treatment in AS patients. METHODS: Twenty-two AS patients under long-term anti
      TNF therapy were evaluated (15 anti-TNF responders and 7 nonresponders). A wide
      range of cell subtypes was analyzed with flow cytometry and compared with therapy
      naive and short-term data too. RESULTS: Key findings include decreased
      proportions of naive CD4 and CD8 cells, increased frequencies of Th1 and Th17
      cells and higher Th1/Th2 ratios in the long-term anti-TNF-treated patients
      (responders, nonresponders and total), which was found to be significant not only
      when compared with healthy controls, but also with therapy-naive and short-term
      anti-TNF-treated AS patients. We noted several alterations within the various
      activated T-cell subsets - increase in CD4HLADR cells in responders, in CD8HLADR
      cells in the whole AS group and in responders, and in CD4CD25 cells in
      responders, and decrease in CD4CD69 cell percentages in long-term treated
      patients - becoming evident only after long-term anti-TNF therapy. CONCLUSIONS:
      This study provides a comprehensive assessment of the impact of anti-TNF therapy
      on the T-cell repertoire in AS. Changes in T-cell phenotype seem to develop
      progressively during therapy, even in inactive disease, and reflect an ongoing
      effector T-cell differentiation and activation, along with the parallel
      compensatory increase in regulatory T cells.

PMID- 29212087
TI  - Knowledge and Sociodemographic Determinants of Emergency Management of Dental
      Avulsion among Parents in Kuwait: A Cross-Sectional Study.
AB  - OBJECTIVES: The aim of this study was to evaluate the knowledge of first aid
      measures for a permanent tooth avulsion among parents in Kuwait and to assess the
      effect of different sociodemographic characteristics. MATERIALS AND METHODS: A
      cross-sectional study was conducted among 554 parents who visited 5 dental
      specialty centers in Kuwait. Parent sociodemographic data and responses to
      avulsion management questions were collected through a self-administered
      questionnaire. Descriptive and binary logistic regression analyses were used for
      data analysis. RESULTS: In the 554 responses from patients, gaps were identified
      in the following areas: replantation (199, 35.9%), cleaning of the tooth (182,
      32.9%), and transport media (84, 15.2%). Most parents demonstrated satisfactory
      knowledge levels regarding the urgency to seek professional help (391, 70.6%) and
      the first place of contact after the injury (525, 94.8%). Having previous
      information on emergency management of dental avulsion was a significant
      predictor of good knowledge (OR 2.138, 95% CI 1.347-3.395, p = 0.001). Of the 544
      parents, 99 (17.8%) had received information on dental avulsion management: 30
      (30.3%) from the Internet, 19 (19.2%) from books, 12 (12.1%) from television, 6
      (6%) from smart phone applications, 2 (2%) from newspapers, and 30 (30.3%) from
      other sources. CONCLUSION: In this study, parents in Kuwait did not have adequate
      knowledge of emergency management for dental avulsion. Future educational
      campaigns on dental avulsion are urgently needed to educate parents.

PMID- 29212092
TI  - [Family-Centered Care in the ICU].
AB  - Family-centered care in the ICU is a quality criterion of modern intensive care.
      Relatives are not just visitors, caregivers and involved stakeholders, but also
      partners for the medical team, especially when eliciting patient preferences and
      during shared decisionmaking. The move towards family-centered care signifies
      that traditional roles are changing; family-centered care is becoming a critical
      component of optimizing patient outcomes in the ICU.

PMID- 29212086
TI  - Comparative Analyses of Transport Proteins Encoded within the Genomes of
      Bdellovibrio bacteriovorus HD100 and Bdellovibrio exovorus JSS.
AB  - Bdellovibrio, delta-proteobacteria, including B. bacteriovorus (Bba) and B.
      exovorus (Bex), are obligate predators of other Gram-negative bacteria. While Bba
      grows in the periplasm of the prey cell, Bex grows externally. We have analyzed
      and compared the transport proteins of these 2 organisms based on the current
      contents of the Transporter Classification Database (TCDB; www.tcdb.org). Bba has
      103 transporters more than Bex, 50% more secondary carriers, and 3 times as many
      MFS carriers. Bba has far more metabolite transporters than Bex as expected from
      its larger genome, but there are 2 times more carbohydrate uptake and drug efflux
      systems, and 3 times more lipid transporters. Bba also has polyamine and
      carboxylate transporters lacking in Bex. Bba has more than twice as many members
      of the Mot-Exb family of energizers, but both may have energizers for gliding
      motility. They use entirely different types of systems for iron acquisition. Both
      contain unexpectedly large numbers of pseudogenes and incomplete systems,
      suggesting that they are undergoing genome size reduction. Interestingly, all 5
      outer-membrane receptors in Bba are lacking in Bex. The 2 organisms have similar
      numbers and types of peptide and amino acid uptake systems as well as protein and
      carbohydrate secretion systems. The differences observed correlate with and may
      account, in part, for the different lifestyles of these 2 bacterial predators.

PMID- 29212093
TI  - Chewing Function in Children with Repaired Esophageal Atresia-Tracheoesophageal
      Fistula.
AB  - INTRODUCTION:  Feeding problems are common in children with esophageal atresia
      and tracheoesophageal fistula (EA-TEF); however, chewing disorders, which may
      cause inability to intake solid food, have not been evaluated. Therefore, we
      aimed to evaluate the chewing function in children with repaired EA-TEF.
      MATERIALS AND METHODS:  Age, sex, the type of atresia, the type of repair, and
      the time to start oral feeding were recorded. The level of the chewing
      performance was scored according to the Karaduman Chewing Performance Scale
      (KCPS). The International Dysphagia Diet Standardization Initiative (IDDSI) was
      used to determine the tolerated food texture in children. RESULTS:  A group of 30
      patients were included, of which 53.3% was male. The percentages of the isolated
      EA and that of the EA-distal TEF were 40% and 60%, respectively. The median value
      for the time to start oral feeding was 4.5 weeks (min = 1, max = 72). Eleven
      (36.7%) children had chewing disorder. The KCPS scores showed level I in six
      cases, level III in four cases, and level IV in one case. Five children with
      chewing disorder had IDDSI level 3 and six had level 7, along with the sensation
      of stuck food. We found no significant difference between the KCPS scores
      according to the repair type (p = 0.07). The median values of the KCPS scores of
      children with primary repair, delayed repair, and colon interposition were 0 (min
      = 0, max = 4), 0.5 (min = 0, max = 3), 2 (min = 0, max = 3), respectively. A
      significant positive correlation was found between the time to start oral feeding
      and the KCPS scores (r = 0.63, p = 0.001). CONCLUSION:  Chewing disorders can be
      observed in children with EA-TEF, and the type of repair and the delay in oral
      feeding may be related to chewing disorder. Therapeutic maneuvers are needed to
      improve the chewing function in children with EA-TEF.

PMID- 29212094
TI  - [Readiness to Participate in Ambulatory Special Medical Care (ASV): A Critical
      Appraisal - Results of a Survey Amongst Office-Based Oncologists in Germany].
AB  - Background Outpatient specialized care (ASV) is intended to improve
      interdisciplinary, transsectoral care for patients with rare or complex diseases,
      especially cancer. Up to now, only very few such specialized care teams have been
      established. The aim of our study was to evaluate the current state of
      information and participation as well as reasons for the reluctance of office
      based hematologists and oncologists. Methods We conducted a web-based survey
      amongst office-based hematologists and oncologists in Germany and received
      responses from 145 institutions comprising more then 350 doctors working there.
      The questions comprised 22 items concerning the state of information,
      implementation as well as obstacles to participation and evaluation of the ASV.
      Results The majority of the interviewed doctors was well informed about ASV. Only
      a minority was in principle against this concept. 6% of them had already treated
      patients within ASV, 8% had completed the preparation, 16% were in the
      preparation process, 26% were indecisive and 45% had decided not to participate.
      The main reasons for non-participation or barriers were high expenditure and a
      lack of benefit for patients, strategic positioning as well as reimbursement.
      Conclusions Although implemented more than 5 years ago, ASV plays no relevant
      role in patient care. The reluctance seems not to be due to information deficits,
      but rather to obstacles in the participation procedure. Relevant advantages for
      patient care, interdisciplinary communication or reimbursement are not
      anticipated. As long as the current low acceptance to participate in ASV is not
      improved, it cannot unfold its potential.

PMID- 29212095
TI  - [Stroke or no stroke - that's the question].

PMID- 29212096
TI  - [Stroke Mimics and Stroke Chameleons: Differential Diagnosis of Stroke].
AB  - The analysis of misdiagnosis of stroke has become increasingly relevant because
      of the time pressure in the thrombolytic treatment of ischemic strokes. Within
      the narrow time window of thrombolysis, a false-positive stroke diagnosis can
      lead to a faulty and potentially dangerous thrombolysis. The terms "Stroke Mimic"
      (SM = false-positive stroke diagnosis) and "Stroke Chameleon" (SC = false
      negative stroke diagnosis) have been introduced for misdiagnosis in this field.
      The rate of SM decreases during the treatment phases from approximately 50 % in
      the preclinical situation to approximately 2-10 % in the Stroke Unit indicating
      thrombolytic therapy. The complication rate for not indicated thrombolysis in SM
      is low with 0.5 % for intracranial bleeding and 0.3 % for orolingual edema. Thus,
      the net balance in favour of fast thrombolysis is maintained, even when a higher
      number of mis-indicated lyses occurs in SM. The rate of SC during the stages of
      treatment drops from about 50 % in the preclinical stage to about 2-5 % in stroke
      units. The rates of SM and SC are inversely linked: a reduction in the SM rate
      leads to a more critical diagnosis of stroke, thus increasing the number of
      underdiagnosed stroke cases as SC, and vice versa. While SM rarely lead to the
      legal consequences of treatment error, SC often give rise to accusations of
      medical errors.

PMID- 29212098
TI  - Immunosuppression following liver transplantation and the course of inflammatory
      bowel disease - a case control study.
AB  - AIM: The aim of this study was to investigate the influence of immunosuppression
      following orthotopic liver transplantation (OLT) on course of inflammatory bowel
      disease (IBD) including disease activity and complications. METHODS: Out of 1168
      patients undergoing liver transplantation between 1988 and 2000 at our center, we
      identified those with IBD (n = 67). In a comparative cohort study, IBD patients
      after OLT were compared to controls without OLT. All drugs including
      immunosuppressive and anti-inflammatory medication and complications during
      follow-up were recorded in 6-month intervals. Also, surgical interventions before
      and after OLT as well as endoscopic interventions with macroscopic and
      microscopic findings were collected and analyzed. Additionally, development of
      malignant neoplasias was recorded. RESULTS: Of the 67 individuals with IBD and
      OLT, 41 were available for analyses and compared with 42 controls. The mean
      follow-up was 7.4 (range: 3 - 15) years. Short-term therapy with calcineurin
      inhibitors or mycophenolate mofetil led to short-term remission, yet sustained
      remission could only be achieved in patients receiving mycophenolate mofetil. At
      14.5 years, clinical remission was reached by significantly more patients in the
      transplant group (54 %) than in the control group (33 %, p = 0.0295). Patients in
      the control group required nearly 2 times as many surgical interventions related
      to IBD than patients in the transplant group. Neoplasias were more common in the
      OLT (n = 8) compared with 4 solid organ cancers in the control group,
      respectively. CONCLUSIONS: Our data demonstrate an overall positive impact of
      immunosuppression following OLT on the course of IBD, especially with
      mycophenolate mofetil, but an increased rate of malignancies.

PMID- 29212099
TI  - ?

PMID- 29212100
TI  - Lower prevalence of vitamin D insufficiency in German patients with systemic mast
      cell activation syndrome compared with the general population.
AB  - Introduction The common mastocytosis variant systemic mast cell activation
      syndrome (MCAS) may underlie at least a subset of patients with irritable bowel
      syndrome (IBS). A critical role of vitamin D (VD) in the stabilization of mast
      cells (MCs) with deficiency of VD resulting in MC activation has been
      demonstrated. If so, supplementation of VD would be a potential therapeutic
      approach in the treatment of those IBS patients. Methods We investigated in the
      present study for the first time systematically whether the VD level in 100 MCAS
      patients differed from that in the German general population (Ggp) and made a
      first attempt to elucidate potential reasons for possible differences by
      simultaneously determining the blood levels of heparin and cholesterol. Results
      In contrast to the Ggp, the VD level was detected in a sufficient range (> 30
      ng/mL) in 53 % of the MCAS patients (Ggp 8 %), and only 34 % had values in the
      range of deficiency (< 20 ng/mL; GgP 75 %). There was no correlation between VD
      blood level and heparin and cholesterol blood levels. Conclusions The
      demonstration that in the majority of MCAS patients the VD level is not in a
      deficient range argues against an essential contribution of VD deficiency to the
      high prevalence of MCAS in Germany. Our findings do not exclude the possibility
      of smaller effects of VD level on MC activation in vivo. However, if such effects
      are present, the effect sizes seem to be too small to become identifiable in the
      multifactorial process of disease development.

PMID- 29212101
TI  - Invitation letters increase participation in colorectal cancer screening -
      results from an observational study.
AB  - Background and Aim Participation rates in the German colorectal cancer screening
      program are low. Starting in 2013, a large health insurance plan in Bavaria,
      Germany, is sending an additional invitation letter to insured individuals when
      they turn 50 or 55 years and become eligible for participation in the program.
      The letter provides detailed information on colorectal cancer screening. We
      assessed the impact of the invitation letter on utilization rates. Methods
      Insurance claims data of a total of 48 343 individuals who had turned 50 or 55
      years between 2012 to 2014 were reviewed for utilization rates of screening
      colonoscopy and fecal blood tests. Utilization rates 1 year prior (2012) and 2
      years after introduction of the invitation letter (2013 and 2014) were compared.
      Furthermore, providers of colorectal cancer screening were determined. Results
      Within 6 months after turning 50 or 55 years, 8.8 - 10.2 % of all insured
      individuals participated in colorectal cancer screening, with the majority being
      females. After the introduction of the invitation letter, a moderate increase in
      participation rates could be observed (increase to 109 % [RR 101.7 - 117.3 %, p =
      0.02] in 2014). The uptake rate of screening colonoscopy was significantly higher
      in recipients of the letter (increase to 138.4 % [RR 110.4 - 173.8 %, p = 0.0043]
      in 2013 and to 149 % [RR 119.5 - 186.3 %, p = 0.0003] in 2014). Furthermore, a
      significantly higher proportion of general practitioners and gastroenterologists
      provided colorectal cancer screening in individuals receiving the invitation
      letter. Conclusions Introduction of an invitation letter can improve
      participation rates for colorectal cancer screening.

PMID- 29212102
TI  - [Conservative treatment of an aseptic abscess syndrome with splenic abscesses in
      Crohn's disease].
AB  - A 24-year old woman with a history of Crohn's disease developed bloody diarrhea
      and multiple abdominal abscesses, daily fever, leukocytosis, and elevated CRP
      several months after her immunosuppressive therapy with azathioprine was stopped.
      Recurrent abscess punctures did not detect any pathogenic germs and neither
      clinical nor serological response was achieved by administration of different
      antimicrobial therapies. Additionally, new splenic abscesses arose despite
      ongoing therapy. Under the suspicion of the rare aseptic abscess syndrome,
      representing an auto-inflammatory, extra-intestinal manifestation of Crohn's
      disease, the antimicrobial therapy was stopped and an intravenous therapy with
      prednisolone was initiated. As soon as therapeutic response was achieved, an
      additional anti-TNF therapy with Infliximab was started and subsequently the
      intraabdominal and splenic abscesses disappeared.The knowledge of the aseptic
      abscess syndrome, which is characterized by (a) sterile abscesses with
      neutrophilic granulocytes, (b) negative blood cultures, (c) lack of response to
      antimicrobial treatment, and (d) rapid clinical improvement after initiation of
      prednisolone therapy with subsequent response in imaging, may avoid unnecessary
      operations like splenectomy in the present case. The exact pathophysiology of the
      aseptic abscess syndrome is unknown but, with regard to the sterile aspirates, an
      auto-inflammatory cause has been suggested. Data of a French case collection
      demonstrate that this syndrome may be present more frequently than expected in
      patients with chronic inflammatory bowel diseases. Up to now, this syndrome has
      not been described in German literature.

PMID- 29212103
TI  - Recurrent diffuse gastric bleeding as a leading symptom of gastrointestinal AL
      amyloidosis.
AB  - Amyloidosis is a rare disease (incidence about 0.8/100 000) characterized by
      extracellular tissue deposition of fibrils composed of low molecular weight
      subunits of a variety of serum proteins. Clinical manifestations are largely
      determined by the type of precursor protein, the tissue distribution and the
      amount of amyloid deposition. Gastrointestinal (GI) manifestations of amyloidosis
      are even more uncommon (3 % of all amyloidosis patients). Symptoms of GI
      amyloidosis are nonspecific, heterogeneous, and include weight loss, GI bleeding,
      heartburn, early satiety, diarrhea and abdominal pain. The histopathological
      examination of biopsy specimens from the GI tract leads to the diagnosis.Herein
      we report the case of a 63-year-old woman with recurrent diffuse gastric
      bleeding. Endoscopic biopsies revealed distinct amyloid deposits in the mucosa of
      the stomach. Further histochemical assessment confirmed systemic light chain (AL)
      amyloidosis with clinically predominant gastrointestinal manifestation. An
      induction therapy with bortezomib and dexamethasone was initiated.Our report
      illustrates the importance of the multidisciplinary approach for diagnosis and
      management of AL amyloidosis. Current treatment of systemic AL amyloidosis is
      based on cytostatic targeting of immunoglobulin producing plasma cells.
      Therapeutic options are limited and highly toxic, making the development of novel
      treatment approaches an urgent need.

PMID- 29212104
TI  - ?

PMID- 29212105
TI  - [German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS)
      position statement on endoscopic decompression in acute Ileus].
AB  - In patients with ileus with dilated intestine in imaging studies, endoscopic
      decompression appears a feasible option. However, its use is often uncritical and
      without scientific evidence. Before considering endoscopic intervention, CT
      imaging should differentiate between mechanical obstruction and paralytic
      ileus/intestinal pseudo-obstruction. Tumor diagnosis and localisation are
      essential because the latter determines the choice of the decompression
      procedure. Coecal dilatation of more than 12 cm indicates an increased risk of
      perforation. In patients with toxic megacolon, dilation of the transverse colon
      to more than 6 cm is considered critical without much prospective evidence.
      Endoscopic decompression has a high complication rate and should be performed
      electively, and not as an emergency procedure, whenever possible. The use of CO2
      insufflation rather than ambient air is strongly recommended, as is the
      availability of fluoroscopy. Prior trans-nasal or oral decompression-tube
      placement is routinely performed, and tracheobronchial intubation frequently
      required. In over 90 % of patients with pseudo-obstruction, conservative
      treatment is successful within 24 to 48 hours, and endoscopic decompression is,
      therefore, unnecessary. Placement of self-expanding metal stents to decompress a
      tumor stenosis is considered mostly for the left colon and rectum and burdened
      with significant risks of perforation and stent migration. Stent impact on
      oncological outcome is controversial because of possible tumor cell mobilization
      and increased postoperative cancer recurrence rates. Surgery, as primary
      intervention, achieves its objective in most cases. Decompression effect by
      endoscopic suctioning of gas and intestinal fluid is usually transient so that it
      is combined with transrectal decompression tubes insertion. This paper reviews
      the advantages and flaws of various decompression procedures in different
      clinical settings.

PMID- 29212106
TI  - [An Uncommon Case of Pneumonia].
AB  - Pneumocystis jirovecii pneumonia is a common cause of respiratory disease in
      immunocompromised hosts. We describe a case of an HIV negative, immunocompetent
      patient and discuss the probable cause.

PMID- 29212107
TI  - [Expenditure on the Care of COPD Patients Under Everyday Conditions in
      Pneumological Practices Differentiated According to Patients in Chronic Care and
      New Patients and Severity of the Illness].
AB  - New patients in the secondary respiratory care require more time for the first
      consultation and place a higher diagnostic and therapeutic demand if compared to
      patients already in chronic care. More diagnostic procedures and patient's
      education by the team are required. No such burden is observed regarding
      differential degrees of severity of respiratory diseases, e. g. COPD. The overall
      demands add up to twice the demands of patients already in care. Thus the time
      required for the treatment of 50 new patients allows consultations for 100
      patients already known in the office.As additional time and effort for new
      patients is not adequately represented in the German medical tax (EBM) a trend to
      risk selection and a preference for control patients is observed. In contrast
      incentives to foster treatment of new patients could be an effective measure to
      dramatically reduce waiting time for visits with pulmonologists. This should be
      achieved by changes in the German medical tax (EBM).

PMID- 29212108
TI  - [The Aut-idem Rule and the Importance of Patient-Individual Selection of Inhalers
      for the Therapy of Airway Diseases in Practices of Pneumologists and General
      Practitioners - Assessment and Implementation by Pneumologists and General
      Practitioners].
AB  - Drug therapy of obstructive airway diseases mainly relies on inhaled medication.
      The success of this therapy depends primarily on the selection of the appropriate
      inhaler considering patient's choice and the correct application. The aut-idem
      rule, an active exclusion of the optional substitution by the pharmacist, allows
      prescribing physicians to ensure the delivery of a particular inhaler, which was
      selected for that patient, who was trained to use specifically that inhaler. This
      survey shows that pneumologists and, to a greater extent general practitioners,
      do not consistently make use of this option, although they unanimously agree on
      the importance of targeted inhaler selection. As a result, patients may receive
      different inhalers in the pharmacy, where the inhaler is chosen under
      consideration of market-driven aspects such as rebate contracts or stock. This
      causes that patients get confused by the exchange of their inhaler. Thus the
      exchange of the inhaler by the pharmacist leads to uncertainty and application
      problems in patients. Hence, the success of the comparatively complex inhaled
      therapy is endangered. This could be prevented, if prescribing physicians were
      informed and supported consistently regarding the use of aut-idem exclusion to
      ensure an optimal therapy for each individual patient.

PMID- 29212109
TI  - Measuring Dabigatran Levels: What Tests Are Available and What Still Needs to Be
      Done?

PMID- 29212110
TI  - Antithrombotic Therapy in Atrial Fibrillation Associated with Valvular Heart
      Disease: Executive Summary of a Joint Consensus Document from the European Heart
      Rhythm Association (EHRA) and European Society of Cardiology Working Group on
      Thrombosis, Endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac
      Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia
      Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association
      and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia
      (SOLEACE).
AB  - Management strategies for patients with atrial fibrillation (AF) in association
      with valvular heart disease (VHD) have been less informed by randomized trials,
      which have largely focused on 'non-valvular AF' patients. Thromboembolic risk
      also varies according to valve lesion and may also be associated with CHA2DS2
      VASc score risk factor components, rather than only the valve disease being
      causal.Given the need to provide expert recommendations for professionals
      participating in the care of patients presenting with AF and associated VHD, a
      task force was convened by the European Heart Rhythm Association (EHRA) and
      European Society of Cardiology (ESC) Working Group (WG) on Thrombosis, with
      representation from the ESC WG on Valvular Heart Disease, Heart Rhythm Society
      (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart)
      Association and Sociedad Latinoamericana de Estimulacion Cardiaca y
      Electrofisiologia (SOLEACE) with the remit to comprehensively review the
      published evidence, and to produce a consensus document on the management of
      patients with AF and associated VHD, with up-to-date consensus statements for
      clinical practice for different forms of VHD, based on the principles of evidence
      based medicine.This is an executive summary of a consensus document which
      proposes that the term 'valvular AF' is outdated and given that any definition
      ultimately relates to the evaluated practical use of oral anticoagulation (OAC)
      type, we propose a functional EHRA (Evaluated Heartvalves, Rheumatic or
      Artificial) categorization in relation to the type of OAC use in patients with
      AF, as follows: (1) EHRA (Evaluated Heartvalves, Rheumatic or Artificial) type 1
      VHD, which refers to AF patients with 'VHD needing therapy with a vitamin K
      antagonist (VKA)' and (2) EHRA (Evaluated Heartvalves, Rheumatic or Artificial)
      type 2 VHD, which refers to AF patients with 'VHD needing therapy with a VKA or a
      non-VKA oral anticoagulant also taking into consideration CHA2DS2-VASc score risk
      factor components.

PMID- 29212111
TI  - Pathophysiological Mechanisms of Endogenous FVIII Release following Strenuous
      Exercise in Non-severe Haemophilia: A Review.
AB  - Introduction Non-severe haemophilia A is characterized by coagulation Factor VIII
      activity (FVIII:C) levels of 1 to 40 IU/dL. It has been reported that strenuous
      exercise increases the plasma FVIII:C in haemophilia A patients. This review
      highlights current knowledge about the pathophysiological mechanisms of
      endogenous FVIII release following strenuous exercise.Methods A literature search
      was performed to include relevant studies with data on pathophysiological
      mechanisms of FVIII release following strenuous exercise in haemophilia.Results
      The source of the released FVIII is most likely endothelial cells (ECs) from
      different vascular beds. ECs from human lung, lymph, heart, intestine, skin and
      pulmonary artery can release and even produce FVIII in response to activation by
      epinephrine. Ex vivo evidence suggests that FVIII is co-stored with von
      Willebrand factor in Weibel-Palade bodies in some forms of non-severe
      haemophilia. The beta-adrenergic receptor pathway is involved in increased FVIII
      levels following strenuous exercise.Conclusion The current available ex vivo and
      in vivo evidence suggests that endogenous FVIII is released by ECs from different
      vascular beds in response to epinephrine following strenuous exercise in patients
      with non-severe haemophilia.

PMID- 29212112
TI  - Incidence of Venous Thromboembolism in Asian Populations: A Systematic Review.
AB  - Introduction Despite a marked recent increase in the number of publications
      describing the incidence of venous thromboembolism (VTE) in Asia, and especially
      in mainland China, Hong Kong, Taiwan, Korea, Japan and Singapore, there remains a
      lack of consensus on the true risks, and trends over time, to inform appropriate
      clinical practice. The purpose of this systematic review was therefore to examine
      evidence about the incidence of symptomatic VTE in Asia.Methods Databases were
      searched for studies from Asia, published between January 1995 and February 2016,
      on the incidence of symptomatic VTE, deep vein thrombosis (DVT) or pulmonary
      embolism. Review of eligible studies was conducted independently by two
      reviewers. Data were extracted on incidence, predispositions and recurrence of
      VTE.Results One thousand nighty-five studies were identified, of which 73 were
      eligible for full text review and data extraction. Three population-wide
      estimates of VTE rates identified from Korea, Taiwan and Hong Kong reported
      annual incidences of 13.8, 15.9 and 19.9 per 100,000, respectively. Nine studies
      of Asian hospital registries or databases reported VTE rates ranging from 11 to
      88 cases per 10,000 admissions. Population-based estimates of post-surgical DVT
      rates ranged from 0.15 to 1.35%. Age was a significant risk factor for VTE in all
      population groups.Conclusion Population-wide incidence estimates in Asia were
      approximately 15 to 20% of the levels recorded in western countries but have
      increased over time. It is anticipated this synthesis of evidence on the
      incidence of VTE and its predisposing factors will increase awareness about VTE
      in Asian populations.

PMID- 29212113
TI  - Assessing Bleeding Risk in Atrial Fibrillation Patients: Comparing a Bleeding
      Risk Score Based Only on Modifiable Bleeding Risk Factors against the HAS-BLED
      Score. The AMADEUS Trial.
AB  - Background The HAS-BLED (hypertension, abnormal renal/liver function, previous
      stroke, bleeding history or predisposition, labile international normalized ratio
      [INR], elderly and drugs/alcohol consumption) score has been validated in several
      scenarios but the recent European guidelines does not recommend any clinical
      score to assess bleeding risk in atrial fibrillation (AF) patients and only focus
      on modifiable clinical factors.Purpose The aim of this study was to test the
      hypothesis that the HAS-BLED score would perform at least similarly to an
      approach only based on modifiable bleeding risk factors (i.e. a 'modifiable
      bleeding risk factors score') for predicting bleeding events.Methods We performed
      a comparison between the HAS-BLED score and the new 'modifiable bleeding risk
      factors score' in a post hoc analysis in 4,576 patients included in the AMADEUS
      trial.Results After 347 (interquartile range, 186-457) days of follow-up, 597
      patients (13.0%) experienced any clinically relevant bleeding event and 113
      (2.5%) had a major bleeding. Only the HAS-BLED score was significantly associated
      with the risk of any clinically relevant bleeding (Cox's analysis for HAS-BLED >=
      3: hazard ratio 1.38; 95% confidence interval [CI], 1.10-1.72; p = 0.005). The
      'modifiable bleeding risk factors score' >= 2 were non-significantly associated
      with any clinical relevant bleeding. The two scores had modest ability in
      predicting bleeding events. The HAS-BLED score performed best in predicting any
      clinically relevant bleeding (c-indexes for HAS-BLED, 0.545 [95% CI, 0.530-0.559]
      vs. the 'modifiable bleeding risk factors score', 0.530 [95% CI, 0.515-0.544]; c
      index difference 0.015, z-score = 2.063, p = 0.04). The HAS-BLED score with one,
      two and three modifiable factors performed significantly better than the
      'modifiable bleeding risk factors scores' with one, two and three modifiable risk
      factors.Conclusion When compared with an approach only based on modifiable
      bleeding risk factors proposed by European Society of Cardiology (ESC) AF
      guidelines, the HAS-BLED score performed significantly better in predicting any
      clinically relevant bleeding in this clinical trial cohort. While modifiable
      bleeding risk factors should be addressed in all AF patients, the use of a formal
      bleeding risk score (HAS-BLED) has better predictive value for bleeding risks,
      and would help decision-making in identifying 'high risk' patients for scheduling
      reviews and follow-up.

PMID- 29212114
TI  - Use of Bypassing Agents and Risk of Thromboembolic Events in Patients with
      Haemophilia and Inhibitors.
AB  - Patients with haemophilia and inhibitors to factors VIII or IX require bypassing
      therapy. The primary safety concern of bypassing agents is thromboembolism;
      however, the incidence of thromboembolic adverse events (TAEs) in haemophilia
      patients with inhibitors remains poorly characterized. The aim of this study was
      to assess the incidence of TAEs following exposure to bypassing agents in
      patients with haemophilia. Using U.S. Medicaid database (2000-2010), we
      identified a cohort of 719 males (mean age: 10 years at cohort entry) with
      haemophilia A or B and use of either recombinant factor VIIa (rFVIIa) or
      activated prothrombin complex concentrate (aPCC). Patients were followed up until
      loss of insurance eligibility, end of study period, or the first occurrence of
      TAE. Exposure was assessed on as-treated basis, and outcomes were adjudicated
      through review of healthcare claims. During the observation of a total of 2,823
      person-years (py; mean follow-up: 3.9 years), 22 TAEs were identified, leading to
      incidence rates of 4.2 events (95% confidence interval [CI]: 1.8-8.3) per 1,000
      unexposed py; 15.4 events (95% CI: 6.7-30.3) per 1,000 aPCC-exposed py; 18.2
      events (95% CI: 8.3-34.6) per 1,000 rFVIIa-exposed py; and 29.7 events (95% CI:
      6.1-86.7) per 1,000 py of concomitant exposure to both agents. The results were
      consistent across sensitivity analyses. In conclusion, we found no difference in
      the rate of TAEs across agents, but the data are compatible with a possibly
      increased rate associated with a combination therapy, highlighting the need for
      continuing safety monitoring through prospective registries or observational
      data.

PMID- 29212115
TI  - Risk Factors for the Progression from Low to High Titres in 260 Children with
      Severe Haemophilia A and Newly Developed Inhibitors.
AB  - In children with severe haemophilia A, inhibitors to factor VIII (FVIII) usually
      develop during the first 50 treatment exposure days and are classified as low or
      high titre depending on the peak inhibitor titre being greater or less than 5
      Bethesda units/mL (BU/mL). Classification of the inhibitor may change with time,
      as some low-titre inhibitors progress to high titre following re-exposure to
      FVIII concentrate. The aim of this study was to investigate potential risk
      factors for such a progression in children with severe haemophilia A and newly
      diagnosed inhibitors. This study was a follow-up study of the PedNet Registry and
      included 260 children with severe haemophilia A and inhibitors born between 1990
      and 2009 and recruited consecutively from 31 haemophilia centres. Clinical and
      laboratory data were collected from the date of each child's first positive
      inhibitor test for at least 3 years. At the time of first positive inhibitor
      test, 49% (n = 127) had low-titre inhibitors, with 50% of them progressing to
      high titre and only 25% maintaining low titres. The FVIII gene (F8) mutation type
      was known in 247 patients (95%), and included 202 (82%) null mutations. The
      progression to high-titre inhibitors was associated with null F8 mutations (odds
      ratio [OR]: 2.6; 95% confidence interval [CI]: 1.0-6.5), family history of
      inhibitors (OR: 7.2; 95% CI: 1.8-28.4) and the use of high-dose immune tolerance
      induction, defined as >=100 IU FVIII concentrate/kg/d (OR: 3.9; 95% CI: 1.5
      10.0). These results suggest that high-dose immune tolerance induction should be
      avoided as the initial strategy in patients who develop low-titre FVIII
      inhibitors.

PMID- 29212116
TI  - Refinement of Mouse Protocols for the Study of Platelet Thromboembolic Responses
      In Vivo.
AB  - Mouse models of thromboembolism are frequently used to investigate platelet
      function in vivo and, according to European Union (EU) legislation, must be
      conducted in the context of replacement, refinement and reduction. We have
      previously developed a refined real-time mouse model of thromboembolism as an
      alternative to models of thromboembolic mortality which inflict considerable pain
      and suffering. Real-time monitoring involves infusion of radiolabelled platelets
      into the circulation of anaesthetized mice, and platelet aggregation is measured
      as increases in platelet-associated counts in the pulmonary vasculature following
      injection of platelet agonists. This gives a definitive data set on the tissue
      localization and extent of platelet activation. We developed an additional, more
      simplistic alternative to mortality models based on blood microsampling which
      entails the measurement of circulating platelet counts following agonist
      stimulation. Blood microsamples were collected from the tail vein of
      anaesthetized mice at three different time points leading to a reduction in
      animal numbers. Platelet counts significantly dropped 1 minute after stimulation
      with collagen or thrombin and were restored over 10 minutes. These results
      correlate with those obtained via real-time monitoring and were confirmed by
      immunohistochemistry. Pre-treatment of mice with aspirin significantly inhibited
      the decrease in platelet counts following collagen. These data suggest that blood
      microsampling may be implemented as a simplistic refined alternative to mortality
      models of thromboembolism when specialized monitoring equipment, or use of
      radioactive isotopes for real-time monitoring, which remains the 'gold standard',
      is not feasible. Microsampling refines and reduces animal procedures in
      compliance with current EU legislation.

PMID- 29212117
TI  - Renal Function, Time in Therapeutic Range and Outcomes in Warfarin-Treated Atrial
      Fibrillation Patients: A Retrospective Analysis of Nationwide Registries.
AB  - Patients with severely reduced renal function have been excluded from randomized
      controlled trials of oral anticoagulation in atrial fibrillation (AF). Warfarin
      treatment in this population is controversial and data on anticoagulation control
      and the impact on adverse outcomes are needed. By individual-level linkage of
      nationwide registries, we identified all patients discharged from hospitals with
      AF in Denmark between 1997 and 2011. Patients with available serum creatinine
      tests were categorized according to the estimated glomerular filtration rate
      (eGFR). Time in therapeutic range (TTR) was calculated using the Rosendaal
      method. The risk of stroke and bleeding was estimated using multivariable Cox
      regression analyses with eGFR and TTR estimated time dependently throughout
      follow-up. We identified 10,423 warfarin-treated AF patients with available
      international normalized ratio and creatinine tests; 5,527 with eGFR > 60
      mL/min/1.73 m2, 4,524 with eGFR 30-60 mL/min/1.73 m2 and 372 with eGFR < 30
      mL/min/1.73 m2. Median TTR was 66.7, 61.2 and 49.7% in patients with eGFR > 60,
      30-59 and <30 mL/min/1.73 m2, respectively. A TTR < 70% was associated with a
      higher risk of stroke/thromboembolism (hazard ratio [HR]: 1.39; 95% confidence
      interval [CI]: 1.20-1.60) and bleeding (HR: 1.22; 95% CI: 1.05-1.42) among
      patients with eGFR of 30 to 59 and a trend towards higher risk of
      stroke/thromboembolism (HR: 1.24; 95% CI: 0.86-1.80) and bleeding (HR: 1.17; 95%
      CI: 0.83-1.65) among patients with eGFR < 30 mL/min/1.73 m2. In conclusion,
      warfarin-treated AF patients with reduced renal function have suboptimal
      anticoagulation control which was related to the risk of adverse outcomes.

PMID- 29212118
TI  - Myeloperoxidase Is a Negative Regulator of Phospholipid-Dependent Coagulation.
AB  - Myeloperoxidase (MPO) is a cationic heme enzyme stored in neutrophilic
      polymorphonuclear leukocytes (PMNs) that has recently been implicated in
      inflammatory cell signaling and tissue damage. Although PMNs play a critical role
      in both innate immunity and vascular thrombosis, no previous study has
      systematically investigated the effect of MPO on blood coagulation. Here, we show
      that PMN-derived MPO inhibits the procoagulant activity (PCA) of lipidated
      recombinant human tissue factor (rhTF) in a time- and concentration-dependent
      manner that involves, but is not entirely dependent on the enzyme's catalytic
      activity. Similarly, MPO together with its substrate, H2O2, inhibited the PCA of
      plasma microvesicles isolated from lipopolysaccharide (LPS)-stimulated whole
      blood, an effect additive to that of a function blocking TF antibody. Treatment
      of whole blood with LPS or phorbol-myristate-acetate dramatically increased MPO
      plasma levels, and co-incubation with 4-ABAH, a specific MPO inhibitor,
      significantly enhanced the PCA in plasma supernatants. MPO and MPO/H2O2 also
      inhibited the PCA of activated platelets and purified phospholipids (PLs),
      suggesting that modulation of negatively charged PLs, i.e., phosphatidylserine,
      rather than direct interference with the TF/FVIIa initiation complex was
      involved. Consistently, pretreatment of activated platelets with MPO or MPO/H2O2
      attenuated the subsequent binding of lactadherin, which specifically recognizes
      procoagulant PS on cell membranes. Finally, endogenously released MPO regulated
      the PCA of THP1 cells in an autocrine manner dependent on the binding to
      CD11b/CD18 integrins. Collectively, these findings indicate that MPO is a
      negative regulator of PL-dependent coagulation and suggest a more complex role of
      activated PMNs in haemostasis and thrombosis.

PMID- 29212119
TI  - Escitalopram Impairs Thrombin-Induced Platelet Response, Cytoskeletal Assembly
      and Activation of Associated Signalling Pathways.
AB  - Background Serotonin reuptake inhibitors (SSRIs) may impair platelet function.
      Thrombin is a strong platelet agonist causing irreversible aggregation, release
      of granules' contents, cytoskeletal rearrangement and activation of signalling
      pathways. We investigated the effects of the SSRI escitalopram (SCIT) on thrombin
      induced platelet response.Methods Isolated platelets were exposed to SCIT and
      activated with thrombin. We evaluated (1) platelet response by aggregometry and
      flow cytometry; (2) modifications in cytoskeleton proteins and signalling
      pathways by electrophoresis and Western blot; and (3) ultrastructural changes in
      platelets by electron microscopy.Results SCIT inhibited platelet response to
      thrombin, measured as platelet aggregation and expression of activation markers
      CD62-P and CD63 from platelet granules. Platelet aggregation decreased in a dose
      dependent manner, reaching statistical significance with SCIT >=32 ug/mL (65.4 +/
      6.8% vs. 77.7 +/- 2.5% for controls; p < 0.05). Expression of activation markers
      was statistically reduced with SCIT >=20 ug/mL (p < 0.05). SCIT impaired the
      polymerization of the actin cytoskeleton and association of contractile proteins
      during activation with thrombin (p < 0.05 with SCIT >=50 ug/mL). Resting
      platelets incubated with SCIT became most spherical, with increased platelet
      roundness (p < 0.01, SCIT 50 ug/mL vs. control). SCIT interfered with signalling
      pathways modulated by thrombin (RhoA, PKC, Erk1/2 and PI3K/AKT).Conclusions Our
      data indicate that SCIT inhibits thrombin-induced platelet response and
      interferes with cytoskeletal assembly and related signalling pathways, thus
      resulting in compromised release of granules' contents, reduced platelet
      activation and aggregation. These mechanisms may explain the antithrombotic
      benefits observed in patients treated with this SSRI, and could become new
      therapeutic targets for future antithrombotic strategies.

PMID- 29212120
TI  - Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in
      Newborn Mice.
AB  - Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL
      mutations that impair thrombopoietin (TPO) signalling, resulting in a near
      absence of megakaryocytes (MKs). While this phenotype is consistent in adults,
      neonates with CAMT can present with severe thrombocytopaenia despite normal MK
      numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL
      -/- mice. Liver MKs in c-MPL -/- neonates were reduced in number and size
      compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural
      abnormalities not found in adult c-MPL -/- MKs. Platelet counts were lower in c
      MPL -/- compared with WT mice at birth and did not increase over the first 2
      weeks of life. In vivo biotinylation revealed a significant reduction in the
      platelet half-life of c-MPL -/- newborn mice (P2) compared with age-matched WT
      pups, which was not associated with ultrastructural abnormalities. Genetic
      deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet
      half-life of c-MPL -/- newborn mice, suggesting that it was due to factors other
      than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent
      protein transgenic) platelets transfused into thrombocytopenic c-MPL -/- P2 pups
      also had a shortened lifespan, indicating the importance of cell-extrinsic
      factors. In addition, neonatal platelets from WT and c-MPL -/- mice exhibited
      reduced P-selectin surface expression following stimulation compared with adult
      platelets of either genotype, and platelets from c-MPL -/- neonates exhibited
      reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin
      compared with age-matched WT platelets. Taken together, our findings indicate
      that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and
      developmental stage-specific defects in platelet function.

PMID- 29212121
TI  - Erythrocyte Membrane Fluidity Alterations in Sudden Sensorineural Hearing Loss
      Patients: The Role of Oxidative Stress.
AB  - Introduction Sudden sensorineural hearing loss (SSNHL) involves an acute
      unexplained hearing loss, nearly always unilateral, that occurs over less than a
      72-hour period. SSNHL pathogenesis is not yet fully understood. Cochlear vascular
      occlusion has been proposed as a potential mechanism of hearing damage and
      cochlear ischaemia has been related to alterations of cochlear microvessels. In
      addition, some researchers have focused their attention on the rheological
      alterations and blood hyperviscosity. Erythrocyte deformability plays a key role
      in determining blood viscosity, and it is critical to cochlear perfusion. It has
      been shown that oxidative stress-induced erythrocyte membrane fluidity
      alterations are linked to the progression of cardiovascular diseases.Methods To
      determine whether erythrocytes from SSNHL patients show signs of oxidative
      stress, and whether this condition can modify the haemorheologic profile in these
      patients, we analysed haemorheologic profile and erythrocyte oxidative stress in
      35 SSNHL patients and 35 healthy subjects, matched for age and sex. Fluorescence
      anisotropy was used to evaluate the fluidity of erythrocyte membranes.Results Our
      results show a significant structural and functional involvement of erythrocyte
      membrane alterations in SSNHL, as well as elevated levels of membrane lipid
      peroxidation and intracellular reactive oxygen species (ROS) production. In
      addition, erythrocyte-derived ROS and erythrocyte lipid peroxidation positively
      correlated with whole blood viscosity and erythrocyte deformability. Moreover, in
      vitro experiments demonstrated that ROS display a key role in erythrocyte
      membrane fluidity.Conclusion These findings indicate that erythrocyte oxidative
      stress plays a key role in the pathogenesis of SSNHL and pave the way to new
      therapeutic interventions.

PMID- 29212122
TI  - Levels of Circulating Intermediate Monocytes Decrease after Aortic Valve
      Replacement in Patients with Severe Aortic Stenosis.
AB  - Aortic valve stenosis (AS) is a chronic inflammatory disease. We have previously
      shown that severe AS is associated with increased levels of circulating
      intermediate monocytes. Haemodynamics are considered to influence levels of
      circulating monocyte subsets; we therefore hypothesized that aortic valve
      replacement may result in changes in the distribution of circulating monocyte
      subsets. In the present study, we evaluated levels of circulating monocyte
      subsets in patients with severe AS undergoing surgical aortic valve replacement
      (SAVR) or transcatheter aortic valve replacement (TAVR). Levels of classical
      (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) CD86
      positive monocytes were determined by flow cytometry in peripheral blood of
      patients with severe AS before (baseline) and at 3- and 6-month follow-ups (FUP)
      after SAVR (n = 25 patients) or TAVR (n = 44 patients). Absolute and relative
      levels of circulating intermediate monocytes decreased from median 39.9/uL
      (interquartile range [IQR]: 31.7-53.6/uL) and 6.7% (5.6-8.1%) at baseline to
      31.6/uL (24.3-42.4/uL; p < 0.001) and 5.4% (4.4-6.7%; p < 0.001) at 6-month FUP
      after aortic valve replacement, respectively. The decrease in levels of
      circulating intermediate monocytes appeared earlier (between baseline and 3-month
      FUP) in the TAVR group compared with the SAVR group (between 3- and 6-month FUP).
      In conclusion, levels of circulating intermediate monocytes decrease after SAVR
      or TAVR in patients with severe AS.

PMID- 29212123
TI  - Enrichment of Circulating Endothelial Cells by CD34 Microbeads Followed by
      Enumeration Using Flow Cytometry.
AB  - Background Circulating endothelial cells (CECs) are a potential biomarker of
      angiogenesis. CECs increase in numbers after vessel injury. Higher CEC numbers
      are reported in cancer patients. Most methods for CEC detection and enumeration
      rely on flow cytometry (FCM); however, there is no agreement on CEC phenotype and
      the detection method to be used. This leads to uncertainty about the clinical
      applicability and variation between studies on CEC numbers reported.Objective To
      develop a selective and accurate method for CEC enumeration in peripheral blood
      by enrichment, followed by FCM in healthy volunteers (HV) and cancer
      patients.Methods Samples were enriched using CD34 microbeads, stained with
      nuclear dye and anti-CD14, CD15, CD45, CD34 and CD146 antibodies. Putative CECs
      were examined for Weibel-Palade bodies (WPBs) using anti-von Willebrand factor
      (vWF) antibody and fluorescence microscopy. Linear range of detection (R 2),
      recovery and precision (coefficient of variation percentage [CV%]) were defined
      in three experiments by spiking a known number (range 12-12,800 CECs/4 mL) of
      surrogate endothelial cells in peripheral blood. Sample storage was determined at
      -80 degrees C for up to 2 months.Results Sorted CECs showed vWF in the WPBs. The
      relationship between spiked and detected surrogate cells was R 2 = 1.0, recovery
      of 94.0 to 101.4% and CV% of 1.0 to 18.4%. Recovery +/- standard deviation
      (within-run days 1, 2 and 3) were, respectively, 102.5% +/- 8.2, 97.8% +/- 4.6,
      99.1% +/- 7.7, and after 2 months 94.3% +/- 15.3. The median CECs/mL in patients
      was 24.1 versus 14.4 in HVs.Conclusion This method for selective, sensitive and
      reliable CEC analysis by FCM allows for investigation of CECs as a biomarker in
      clinical research.

PMID- 29212124
TI  - Diagnostic Accuracy of a Novel Chromogenic Direct Thrombin Inhibitor Assay:
      Clinical Experiences for Dabigatran Monitoring.
AB  - Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin
      K antagonists (VKA) for clinical indications requiring long-term oral
      anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran-the
      only direct thrombin inhibitor amongst them-does not require therapeutic drug
      monitoring. However, in case of treatment complications (e.g., major haemorrhage)
      and conditions requiring urgent surgery or thrombolytic therapy, information
      about actual DOAC plasma levels is needed to guide treatment decisions. Due to
      short reagent stability, limited accuracy at low dabigatran levels and high
      heparin sensitivity, the applicability of the widely used Hemoclot thrombin
      inhibitor (HTI) coagulation assay is limited in the emergency setting.Methods
      Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran
      treated patients with drug concentrations of up to 300 ng/mL were measured with
      the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and
      results compared with HTI using ultra performance liquid chromatography-tandem
      mass spectrometry as the reference method for measuring dabigatran plasma
      concentrations.Results BDTI results showed a very strong correlation with
      dabigatran concentrations (r = 0.965, p < 0.0001) as well as a low intra- and
      inter-assay variation of <5%. Compared with HTI, BDTI provides an improved on
      board reagent stability of 72 hours, rapid turnaround times comparable to routine
      coagulation assays, high accuracy at low drug levels and reduced heparin
      sensitivity.Conclusion The BDTI is an ideal coagulation assay for the around-the
      clock determination of dabigatran plasma levels in clinical routine including
      emergency situations.

PMID- 29212125
TI  - Regional Differences in Antithrombotic Treatment for Atrial Fibrillation:
      Insights from the GLORIA-AF Phase II Registry.
AB  - Introduction Although guideline-adherent antithrombotic therapy (ATT) for stroke
      prevention in atrial fibrillation (AF) is associated with lower mortality and
      thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to
      assess thromboembolic risk and baseline ATT by geographic region and identify
      factors associated with prescription of ATT in a large, truly global registry of
      patients with recently diagnosed AF.Methods and Results Our analysis comprises
      15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled
      in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in
      Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC)
      use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East
      (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among
      OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs
      (NOACs) as the more prevalent OAC option in all regions, with highest use in
      North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in
      community hospitals but only 49.8% in university hospitals and 42.6% in
      specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at
      5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were
      prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not
      anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%).Conclusion
      Substantial inter- and intra-regional differences in ATT for stroke prevention in
      AF are evident in this global registry. While guideline-adherent ATT can be
      further improved, NOACs are the main contributor to high OAC use worldwide.

PMID- 29212126
TI  - Thrombus Burden of Deep Vein Thrombosis and Its Association with
      Thromboprophylaxis and D-Dimer Measurement: Insights from the APEX Trial.
AB  - Background The aim of this study was to evaluate the effect of betrixaban on the
      occurrence of deep vein thrombosis (DVT) and also the extent of thrombus and to
      assess the association of baseline D-dimer with subsequent thrombus
      burden.Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely
      ill hospitalized medical patients were randomly assigned to extended-duration
      betrixaban (35-42 days) or enoxaparin (10 +/- 4 days). D-dimer concentration was
      measured at baseline, and mandatory lower-extremity compression ultrasonography
      (CUS) was performed at 35 to 42 days. The thrombus burden of DVT was assessed by
      the number of non-compressible vascular segments in six target proximal veins and
      compared between treatment groups and D-dimer categories (>=2 * upper limit of
      normal [ULN] versus <2 * ULN).Results Compared with enoxaparin, extended-duration
      betrixaban reduced the DVT risk at 35 to 42 days (any-dose: relative risk [RR] =
      0.76 [95% confidence interval: 0.61-0.94]; p = 0.013; full-dose: RR = 0.70 [0.55
      0.90]; p = 0.005). Patients who received betrixaban were more likely to have a
      lower thrombus burden (p = 0.012 for any-dose and p = 0.001 for full-dose).
      Elevated D-dimer at baseline was independently associated with a 2.12-fold
      increased risk of developing DVT (p < 0.001). A greater thrombus burden was also
      observed in those with D-dimer >= 2 * ULN compared with <2 * ULN (p <
      0.0001).Conclusion Extended-duration betrixaban reduced the number of venous
      segments with thrombosis at 35 to 42 days compared with enoxaparin. A positive D
      dimer was associated with a greater extent of thrombus burden among acutely ill
      medical patients who developed DVT despite receiving thromboprophylaxis.

PMID- 29212127
TI  - Low-Dose Aspirin after an Episode of Haemorrhagic Stroke Is Associated with
      Improved Survival.
AB  - We aimed at investigating how antiplatelet drug use affected mortality in
      patients with a history of haemorrhagic stroke (HS). Thus, starting 30 days after
      an HS episode, we followed 1,004 patients with intracerebral haemorrhage (ICH)
      and 929 patients with subarachnoid haemorrhage (SAH) for a median of 6.4 years.
      We estimated the effect of time-dependent exposure to antiplatelets after HS on
      all-cause mortality. Cox proportional hazard models were used to compute adjusted
      hazard ratios (aHRs) and 95% confidence intervals (CI).We found that current use
      of low-dose aspirin was associated with a 32% improved survival (aHR = 0.68; 95%
      CI: 0.53-0.88), with a similar association among ICH (aHR = 0.66; 95% CI: 0.49
      0.89) and SAH (aHR = 0.61; 95% CI: 0.36-1.04) patients. A statistically
      significant improved survival associated with current use of low-dose aspirin
      during follow-up was only observed among individuals who used antithrombotic
      drugs in the year before the HS (prior use: aHR = 0.56; 95% CI: 0.39-0.80; non
      prior use: aHR = 0.87; 95% CI: 0.61-1.24). Current use of clopidogrel was not
      associated with survival (aHR = 1.35; 95% CI: 0.88-2.08). Statin use was
      associated with improved survival (aHR = 0.38; 95% CI: 0.31-0.47). On the other
      hand, discontinuation of statins (aHR = 1.31; 95% CI: 1.02-1.68) or low-dose
      aspirin (aHR = 1.54; 95% CI: 1.21-1.97) was associated with decreased survival.
      In our study, use of low-dose aspirin after an episode of HS to reduce vascular
      risks is safe, particularly in patients who were on antithrombotic therapy before
      the episode. Our results suggest an improved survival associated with low-dose
      aspirin. This finding must be interpreted with care due to the observational
      nature of the study, and warrants further studies.

PMID- 29212128
TI  - Outpatient Management in Patients with Venous Thromboembolism with Edoxaban: A
      Post Hoc Analysis of the Hokusai-VTE Study.
AB  - Direct oral anticoagulants (DOACs) facilitate the outpatient treatment of venous
      thromboembolism (VTE). However, the pivotal trials of DOACs have not reported
      outcomes separately for patients managed either as outpatients or in the
      hospital. We performed a subgroup analysis of the Hokusai-VTE study comparing
      efficacy and safety of edoxaban with warfarin in 8,292 patients with acute VTE.
      Patients received initial therapy with open-label enoxaparin or unfractionated
      heparin for >=5 days in the hospital or as an outpatient at the discretion of the
      treating physician. Edoxaban or warfarin was then given for 3 to 12 months. The
      primary efficacy outcome was the cumulative incidence of symptomatic recurrent
      VTE at 12 months. The principal safety outcome was the incidence of clinically
      relevant bleeding (composite of major or clinically relevant non-major bleeding).
      Of the 5,223 consecutively enrolled patients with recorded hospital status and
      length of stay, 1,414 patients (27.1%) were managed as outpatients and 3,809 were
      managed in hospital. Among the outpatients, initial presentation was symptomatic
      deep-vein thrombosis (DVT) in 1,183 patients (83.7%) and pulmonary embolism (PE)
      in 231 patients (16.3%). Among the outpatients with DVT, recurrent VTE occurred
      in 18 (3.0%) given edoxaban and in 21 (3.6%) given warfarin (risk difference: 
      0.61, 95% confidence interval [CI]: -2.6 to 1.4). The principal safety outcome in
      outpatients occurred in 46 edoxaban patients (7.7%) and in 48 warfarin patients
      (8.3%; risk difference: -0.59, 95% CI: -3.7 to 2.5). Most outpatients had
      symptomatic DVT at presentation. In these patients, initial heparin followed by
      edoxaban had similar efficacy and safety to standard therapy with heparin and
      warfarin.

PMID- 29212129
TI  - The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for
      Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or
      Procedure: Design and Rationale.
AB  - Background The perioperative management of patients who take a direct oral
      anticoagulant (DOAC) for atrial fibrillation and require treatment interruption
      for an elective surgery/procedure is a common clinical scenario for which best
      practices are uncertain. The Perioperative Anticoagulant Use for Surgery
      Evaluation (PAUSE) study is designed to address this unmet clinical need. We
      discuss the rationale for the PAUSE design and analysis plan as well as the
      rationale supporting the perioperative DOAC protocol.Methods PAUSE is a
      prospective study with three parallel cohorts, one for each DOAC, to assess a
      standardized but patient-specific perioperative management protocol for DOAC
      treated patients with atrial fibrillation. The perioperative protocol accounts
      for DOAC type, patient's renal function and surgery/procedure-related bleeding
      risk. The primary study aim is to demonstrate the safety of the PAUSE protocol
      for the perioperative management of each DOAC. The secondary aim is to determine
      the effect of the pre-procedure interruption on residual anticoagulation when
      measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for
      rivaroxaban and apixaban. The study hypothesis is that the perioperative
      management protocol for each DOAC is safe for patient care, defined by expected
      risks for major bleeding of 1% (80% power to exclude 2%), and for arterial
      thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group.Conclusion
      The PAUSE study has the potential to establish a standard-of-care approach for
      the perioperative management of DOAC-treated patients. The PAUSE management
      protocol is designed to be easily applied in clinical practice, as it is
      standardized and also patient specific.

PMID- 29212130
TI  - Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk
      Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.
AB  - Patients with intermediate-risk pulmonary embolism (PE) may, depending on the
      method and cut-off values used for definition, account for up to 60% of all
      patients with PE and have an 8% or higher risk of short-term adverse outcome.
      Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have
      been approved for the treatment of venous thromboembolism, their safety and
      efficacy as well as the optimal anticoagulation regimen using these drugs have
      not been systematically investigated in intermediate-risk PE. Moreover, it
      remains unknown how many patients with intermediate-high-risk and intermediate
      low-risk PE were included in most of the phase III NOAC trials. The ongoing
      Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a
      prospective, multicentre, multinational, single-arm trial investigating whether
      treatment of acute intermediate-risk PE with parenteral heparin anticoagulation
      over the first 72 hours, followed by the direct oral thrombin inhibitor
      dabigatran over 6 months, is effective and safe. The primary efficacy outcome is
      recurrent symptomatic venous thromboembolism or death related to PE within the
      first 6 months. The primary safety outcome is major bleeding as defined by the
      International Society on Thrombosis and Haemostasis. Secondary outcomes include
      all-cause mortality, the overall duration of hospital stay (index event and
      repeated hospitalizations) and the temporal pattern of recovery of right
      ventricular function over the 6-month follow-up period. By applying and
      evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2
      will implement the recommendations of current guidelines and contribute to their
      further evolution.

PMID- 29212131
TI  - Predicting Vaginal Delivery in Nulliparous Women Undergoing Induction of Labor at
      Term.
AB  - OBJECTIVE:  We sought to develop a model to calculate the likelihood of vaginal
      delivery in nulliparous women undergoing induction at term. STUDY DESIGN:  We
      obtained data from the Consortium on Safe Labor by including nulliparous women
      with term singleton pregnancies undergoing induction of labor at term. Women with
      contraindications for vaginal delivery were excluded. A stepwise logistic
      regression analysis was used to identify the predictors associated with vaginal
      delivery by considering maternal characteristics and comorbidities and fetal
      conditions. The receiver operating characteristic curve, with an area under the
      curve (AUC) was used to assess the accuracy of the model. RESULTS:  Of 10,591
      nulliparous women who underwent induction of labor, 8,202 (77.4%) women had
      vaginal delivery. Our model identified maternal age, gestational age at delivery,
      race, maternal height, prepregnancy weight, gestational weight gain, cervical
      exam on admission (dilation, effacement, and station), chronic hypertension,
      gestational diabetes, pregestational diabetes, and abruption as significant
      predictors for successful vaginal delivery. The overall predictive ability of the
      final model, as measured by the AUC was 0.759 (95% confidence interval, 0.749
      0.770). CONCLUSION:  We identified independent risk factors that can be used to
      predict vaginal delivery among nulliparas undergoing induction at term. Our
      predictor provides women with additional information when considering induction.

PMID- 29212132
TI  - Urological laparoendoscopic single-site and reduced port surgery: A nationwide
      survey in Japan.
AB  - OBJECTIVES: To evaluate the current status of urological laparoendoscopic single
      site and reduced port surgery in Japan. METHODS: Of the 152 institutions to which
      councilors of the Japanese Society of Endourology belong, 42 (28%) have carried
      out laparoendoscopic single-site and reduced port surgery. A total of 32 of these
      institutions agreed to participate in this survey. Patients who had undergone
      surgery between January 2008 and March 2014 were included in the present study.
      RESULTS: Overall, 1145 cases of laparoendoscopic single-site and reduced port
      surgery were recorded during the study period. The most frequent procedures were
      adrenalectomy and radical nephrectomy. Laparoendoscopic single-site and reduced
      port surgery represented 12% (872/7311) of all laparoscopic procedures carried
      out at participating institutions. The number of patients who underwent
      pyeloplasty, donor nephrectomy and simple nephrectomy tended to increase, whereas
      those who underwent adrenalectomy, radical nephrectomy and nephroureterectomy
      peaked in 2012, and then tended to decrease in 2013. The rates of conversion,
      perioperative and postoperative complications, were 2.7%, 2.2% and 4.5%,
      respectively. CONCLUSIONS: The number of laparoendoscopic single-site and reduced
      port urological surgeries in Japan has increased for benign indications, such as
      pyeloplasty, donor nephrectomy and simple nephrectomy. In contrast, procedures
      such as adrenalectomy and radical nephrectomy are trending down after reaching a
      peak in 2012. Overall, laparoendoscopic single-site and reduced port urological
      surgery in Japan is being safely carried out when compared with other reported
      series of laparoendoscopic single-site surgery and conventional laparoscopic
      surgery.

PMID- 29212133
TI  - Factors associated with patient-reported procedural memory following emergency
      department procedural sedation with ketamine and propofol: A prospective cohort
      of 563 patients.
AB  - OBJECTIVES: To describe the proportion of patients reporting procedural memory
      following procedural sedation and analgesia (PSA) with ketamine and propofol (KP)
      administered premixed together (ketofol) or individually (sequential KP) in ED
      attendees. Identify any clinical or demographic variables associated with
      procedural memory. METHODS: This was a convenience sample of 563 patients who
      received KP PSA as per the departmental protocol. A standardised script was used
      to assess for procedural memory. This was categorised as 'any' and 'unpleasant'
      prior to discharge (immediate memory) and at telephone follow up (delayed
      memory). RESULTS: A total of 318 patients had sequential KP and 249 premixed 1:1
      ketofol. For sequential KP compared to ketofol, the proportion reporting any
      memory was as follows: 3.5% versus 3.3% immediate, 4.4% versus 5.5% delayed and
      5.4% versus 7.4% for the sum of these. For unpleasant memory, the proportion was
      as follows: 1.6% versus 2.9% immediate, 1.7% versus 4.7% delayed and 2.2% versus
      6.9% all unpleasant memory (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.4
      8.1). Memory was associated with male sex (OR 4, 95% CI 1.5-10.5), opiates (OR 3,
      95% CI 1.7-7.5), a Wisconsin Sedation Scale score >=3 (moderate sedation) (OR
      4.3, 95% CI 1.1-18.2) and propofol dose <0.75 mg/kg compared to >0.75 mg/kg (13%
      versus 3%) (OR 6, 95% CI 1.7-21). The ketofol group had 5% (95% CI 0.1-10) more
      respiratory events requiring intervention. CONCLUSIONS: Procedural memory was
      uncommon for both mix types; however, a greater proportion of the premixed
      ketofol group had unpleasant memory. Associations with sex, opiates, moderate
      sedation and propofol dose were identified, and respiratory adverse events were
      more common in the premixed ketofol group.

PMID- 29212134
TI  - Association between attention bias to threat and anxiety symptoms in children and
      adolescents.
AB  - BACKGROUND: Considerable research links threat-related attention biases to
      anxiety symptoms in adults, whereas extant findings on threat biases in youth are
      limited and mixed. Inconsistent findings may arise due to substantial
      methodological variability and limited sample sizes, emphasizing the need for
      systematic research on large samples. The aim of this report is to examine the
      association between threat bias and pediatric anxiety symptoms using standardized
      measures in a large, international, multi-site youth sample. METHODS: A total of
      1,291 children and adolescents from seven research sites worldwide completed
      standardized attention bias assessment task (dot-probe task) and child anxiety
      symptoms measure (Screen for Child Anxiety Related Emotional Disorders). Using a
      dimensional approach to symptomatology, we conducted regression analyses
      predicting overall, and disorder-specific, anxiety symptoms severity, based on
      threat bias scores. RESULTS: Threat bias correlated positively with overall
      anxiety symptoms severity (beta = 0.078, P = .004). Furthermore, threat bias was
      positively associated specifically with social anxiety (beta = 0.072, P = .008)
      and school phobia (beta = 0.076, P = .006) symptoms severity, but not with panic,
      generalized anxiety, or separation anxiety symptoms. These associations were not
      moderated by age or gender. CONCLUSIONS: These findings indicate associations
      between threat bias and pediatric anxiety symptoms, and suggest that vigilance to
      external threats manifests more prominently in symptoms of social anxiety and
      school phobia, regardless of age and gender. These findings point to the role of
      attention bias to threat in anxiety, with implications for translational clinical
      research. The significance of applying standardized methods in multi-site
      collaborations for overcoming challenges inherent to clinical research is
      discussed.

PMID- 29212136
TI  - Explosive detection using a novel dielectric barrier discharge ionisation source
      for mass spectrometry.
AB  - The detection of explosives is of great importance, as is the need for sensitive,
      reliable techniques that require little or no sample preparation and short run
      times for high throughput analysis. In this work, a novel ionisation source is
      presented based on a dielectric barrier discharge (DBD). This not only affects
      desorption and ionisation but also forms an ionic wind, providing mass
      transportation of ions towards the mass spectrometer. Furthermore, the design
      incorporates 2 asymmetric alumina sheets, each containing 3 DBDs, so that a large
      surface area can be analysed. The DBD operates in ambient air, overcoming the
      limitation of other plasma-based techniques which typically analyse smaller
      surface areas and require solvents or gases. A range of explosives across 4
      different functional groups was analysed using the DBD with low limits of
      detection for cyclotrimethylene trinitramine (RDX) (100 pg), pentaerythritol
      trinitrate (PETN) (100 pg), hexamethylene triperoxide diamide (HMTD) (1 ng), and
      trinitrotoluene (TNT) (5 ng). Detection was achieved without any sample
      preparation or the addition of reagents to facilitate adduct formation.

PMID- 29212135
TI  - What is the effect on comorbid personality disorder of brief panic-focused
      psychotherapy in patients with panic disorder?
AB  - BACKGROUND: No studies of psychotherapies for panic disorder (PD) have examined
      effects on comorbid personality disorders (PersD), yet half such patients have a
      PersD. METHODS: In a randomized trial for PD with and without agoraphobia
      comparing Cognitive-Behavioral Therapy (CBT) and Panic-Focused Psychodynamic
      Psychotherapy (PFPP), PersD was assessed pre-to-post treatment with the
      Structured Clinical Interview for the Diagnosis of Axis-II Disorders (SCID-II).
      For patients completing therapy (n = 118, 54 with PersD), covariance between
      panic and SCID-II criteria improvements was analyzed. SCID-II diagnostic
      remission and recovery were evaluated. Comparative efficacy of PFPP versus CBT
      for improving PersD was analyzed both for the average patient, and as a function
      of PersD severity. RESULTS: 37 and 17% of PersD patients experienced diagnostic
      PersD remission and recovery, respectively. Larger reductions in PersD were
      related to more panic improvement, with a modest effect size (r = 0.28). Although
      there was no difference between treatments in their ability to improve PersD for
      the average patient (d = 0.01), patients meeting more PersD criteria did better
      in PFPP compared to CBT (P = .007), with PFPP being significantly superior at 11
      criteria and above (d = 0.66; 3 more criteria lost). CONCLUSIONS: PersD
      presenting in the context of primary PD rarely resolves during psychotherapies
      focused on PD, and change in PersD only moderately tracks panic improvements,
      indicating non-overlap of the constructs. Patients receiving panic-focused
      psychotherapies may require additional treatment for their PersD. PFPP may be
      superior at improving severe PersD, but replication of this finding is required.

PMID- 29212138
TI  - Direction-Of-Arrival Estimation and Tracking Based on a Sequential Implementation
      of C-SPICE with an Off-Grid Model.
AB  - This paper focuses on the problem of estimating and tracking time-varying
      direction-of-arrivals (DoAs) with an antenna array. A sequential DoA estimation
      method is proposed by extending the capon and sparse iterative covariance-based
      estimation (C-SPICE) method, which is an iterative off-grid method for estimating
      constant DoAs. Then, a moving average initialization technique is introduced such
      that the spatial spectrum information estimated in this snapshot can be utilized
      in the next one. In uniform linear arrays (ULAs), we replace the uniform grid in
      direction domain with that in a "frequency" domain, to improve estimation
      accuracy without additional complexity in practical applications. The validity
      and efficiency of the proposed methods are demonstrated through numerical
      experiments.

PMID- 29212137
TI  - Review article: Idle 'just-in-case' peripheral intravenous cannulas in the
      emergency department: Is something wrong?
AB  - Peripheral intravenous cannula (PIVC) placement is often an essential emergency
      medicine precursor to lifesaving treatment, but it is not harmless. Patients
      frequently and without proper consideration of the consequences receive a 'just
      in-case' PIVCs as part of their assessment and admission, which, in a not
      insignificant number of patients, remains unused or idle in situ. We reviewed the
      literature and performed a thematic analysis of data collated from 21 articles
      published in the past 24 years regarding redundant PIVCs. The following five
      common themes emerged: heterogeneous prevalence data on post-insertion PIVC
      usage, preventable intravascular complications, financial burden, loss of time
      and a culture of over-investigating. The prevalence of PIVC insertions and idle
      PIVCs was heterogeneous among these publications; the median ED idle PIVC
      prevalence value was 32.4%. This practice is associated with compromised patient
      safety, squandered finances and misdirected practitioner time. Cultures of
      convenience and shortfalls in PIVC-related education facilitate the prevalence of
      idle PIVCs.

PMID- 29212140
TI  - Effective models for antimetastatic therapies.

PMID- 29212139
TI  - Surface Plasmon Resonance Sensors on Raman and Fluorescence Spectroscopy.
AB  - The performance of chemical reactions has been enhanced immensely with surface
      plasmon resonance (SPR)-based sensors. In this review, the principle and
      application of SPR sensors are introduced and summarized thoroughly. We introduce
      the mechanism of the SPR sensors and present a thorough summary about the optical
      design, including the substrate and excitation modes of the surface plasmons.
      Additionally, the applications based on SPR sensors are described by the Raman
      and fluorescence spectroscopy in plasmon-driven surface catalytic reactions and
      the measurement of refractive index sensing, especially.

PMID- 29212141
TI  - Cytomegalovirus pulls strings behind NK cells.

PMID- 29212142
TI  - A guilt-by-association mutation network in LGL leukemia.

PMID- 29212143
TI  - Targeting cistrome and dysregulated transcriptome of post-MPN sAML.

PMID- 29212144
TI  - Microbiome genetics underpins chemotherapy.

PMID- 29212145
TI  - Targeting constitutive NF-kappaB specifically in tumor cells.

PMID- 29212146
TI  - Radiotherapy: the key to immunotherapy ignition?

PMID- 29212147
TI  - Blinatumomab in Ph+ B-ALL: present and perspectives.

PMID- 29212148
TI  - Microneedle patch for immunization of immunocompromised hosts.

PMID- 29212149
TI  - The methylated way to translation.

PMID- 29212150
TI  - Combining enzalutamide with PARP inhibitors: Pharmaceutically induced BRCAness.

PMID- 29212151
TI  - DNA non-homologous end-joining enters the resection arena.

PMID- 29212152
TI  - PRPF8 is important for BRCA1-mediated homologous recombination.
AB  - Disruption of RNA splicing causes genome instability, which could contribute to
      cancer etiology. Furthermore, RNA splicing is an emerging anti-cancer target.
      Thus, we have evaluated the influence of the spliceosome factor PRPF8 and the
      splicing inhibitor Pladienolide B (PlaB) on homologous recombination (HR). We
      find that PRPF8 depletion and PlaB treatment cause a specific defect in homology
      directed repair (HDR), and single strand annealing (SSA), which share end
      resection as a common intermediate, and BRCA1 as a required factor. Furthermore,
      PRPF8 depletion and PlaB treatment cause reduced end resection detected as
      chromatin-bound RPA, BRCA1 foci in response to damage, and histone acetylation
      marks that are associated with BRCA1-mediated HR. We also identified distinctions
      between PlaB and PRPF8 depletion, in that PlaB also reduces 53BP1 foci, and BRCA1
      expression. Furthermore loss of 53BP1, which rescues SSA in BRCA1 depleted cells,
      and partially rescues SSA in PRPF8 depleted cells, has no effect on SSA in PlaB
      treated cells. Finally, while PRPF8 depletion has no obvious effect on the
      integrity of interchromatin granules, PlaB disrupts these structures. These
      findings indicate that PRPF8 is important for BRCA1-mediated HR, whereas PlaB
      also has a more general effect on the DNA damage response and nuclear
      organization.

PMID- 29212154
TI  - Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic
      syndrome using a genome-wide association study in a Taiwanese population.
AB  - Background: Although the association of single nucleotide polymorphisms (SNPs)
      with metabolic syndrome (MetS) has been reported in various populations in
      several genome-wide association studies (GWAS), the data is not conclusive. In
      this GWAS study, we assessed whether SNPs are associated with MetS and its
      individual components independently and/or through complex interactions in a
      Taiwanese population. Methods: A total of 10,300 Taiwanese subjects were assessed
      in this study. Metabolic traits such as waist circumference, triglyceride, high
      density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressure, and
      fasting glucose were measured. Results: Our data showed an association of MetS at
      the genome-wide significance level (P < 8.6 x 10-8) with two SNPs, including the
      rs662799 SNP in the apolipoprotein A5 (APOA5) gene and the rs16944558 SNP in the
      collectin subfamily member 12 (COLEC12) gene. Moreover, we identified the effect
      of APOA5 rs662799 on triglyceride and HDL, the effect of rs1106475 in the actin
      filament associated protein 1 like 2 (AFAP1L2) gene on systolic blood pressure,
      and the effect of rs17667932 in the mediator complex subunit 30 (MED30) gene on
      fasting glucose. Additionally, we found that an interaction between the APOA5
      rs662799 and COLEC12 rs16944558 SNPs influenced MetS, high triglyceride, and low
      HDL. Conclusions: Our study indicates that the APOA5 and COLEC12 genes may
      contribute to the risk of MetS and its individual components independently as
      well as through gene-gene interactions.

PMID- 29212153
TI  - Age-related modulation of plasmatic beta-Galactosidase activity in healthy
      subjects and in patients affected by T2DM.
AB  - beta-Galactosidase (beta-Gal) activity has been the most extensively utilized
      biomarker for the detection of cellular senescence. It can be measured also in
      plasma, and few recent evidence showed an altered plasmatic beta-Gal activity in
      patients affected by some age-related diseases (ARDs). Since T2DM is one of the
      most common ARDs, we aimed to investigate if plasmatic beta-Gal activity is
      modulated in T2DM patients and if "age" could affect such modulation. To gain
      mechanistic insights we paralleled this investigation with the evaluation of beta
      Gal activity in young and senescent endothelial cells (HUVECs) cultured in normo-
      and hyper-glycaemic environment. A significant age-related increase of plasmatic
      beta-Gal activity was observed in healthy subjects (n. 230; 55-87 years), whereas
      the enzymatic activity was significantly reduced in T2DM patients (n. 230; 55-96
      years) compared to healthy subjects. beta-Gal activity detectable both in cells
      and in the culture medium was significantly increased in senescent cells compared
      to the younger ones, both under normo- and hyper-glycaemic condition. However,
      the hyper-glycaemic condition was not associated with an increased beta-Gal
      activity in milieu compared to normo-glycaemic condition. Overall our data
      reinforce the notion that plasmatic beta-Gal activity could be a systemic
      biomarker of aging, whereas T2DM patients are characterized by a different age
      releated trend.

PMID- 29212155
TI  - Small molecule-mediated induction of miR-9 suppressed vascular smooth muscle cell
      proliferation and neointima formation after balloon injury.
AB  - Pathologic proliferation and migration of vascular smooth muscle cells (VSMCs)
      exacerbate cardiovascular disease. MicroRNAs (miRNAs), as endogenous inhibitors
      of protein synthesis, are expected to modulate pathologic proliferation of VSMCs.
      Here we report that both platelet-derived growth factor receptor (PDGFR)
      targeting miR-9 and a small molecule that increases miR-9 can inhibit the serum
      induced proliferation of VSMCs. First, based on miRNA-target prediction databases
      and empirical data, we have selected miR-9 as a potent anti-proliferative miRNA
      in VSMCs. Further examination indicated that miR-9 directly targets PDGFR
      disrupting downstream signaling cascades, and this resulted in inhibition of VSMC
      proliferation and migration. Exogenous delivery of miR-9 inhibited VSMC
      proliferation in vitro, and a small molecule that increased miR-9 expression also
      inhibited neointima formation following balloon injury in vivo. We provide
      evidence of miRNA-mediated modulation of VSMC proliferation and further
      demonstrate that small molecule-mediated regulation of miRNA targeting a key
      regulator of VSMC proliferation is a viable therapeutic strategy for treating
      vascular disease involving pathologic VSMC proliferation such as restenosis.

PMID- 29212156
TI  - Effects of cerebral perfusion pressure on regional cerebral blood flow in dogs
      with acute epidural hematoma: quantitative evaluation with contrast-enhanced
      ultrasound.
AB  - To discuss the relationship between the regional cerebral blood flow (rCBF) and
      cerebral perfusion pressure (CPP) and the effect of CPP on rCBF in different
      spaces in an experimental animal model. As the ICP increased, the CPP and rCBF (A
      * beta value measured by CEU) decreased to varying degrees. The rCBF1 and rCBF2
      were well correlated with the CPP. At the same CPP, rCBF1 decreased significantly
      than the level of rCBF2 (p < 0.01). Six healthy cross-breed dogs, both males and
      females, weighing 18.3 +/- 1.6 kg, were selected to establish models of increased
      intracranial pressure (ICP) via the installation of an epidural latex sacculus.
      The calculated CPP was in accordance with the ICP through the formula CPP = MAP -
      ICP, and contrast-enhanced ultrasound (CEU) was used to instantly measure the
      rCBF 1 and 2 cm around the sacculus edge. The relationship between rCBF 1 cm
      (rCBF1) and 2 cm (rCBF2) around the sacculus edge and the CPP was analyzed. As
      the ICP increased, the CPP and rCBF both decreased. The rCBF and the CPP had a
      linear relationship, but the perfusion pressure did not necessarily determine all
      parts of the rCBF. The rCBF was different in different spaces: the farther away
      from the injured site, the smaller the effect on the rCBF.

PMID- 29212157
TI  - PKA activation and endothelial claudin-5 breakdown in the schizophrenic
      prefrontal cortex.
AB  - Schizophrenia is thought to be caused by a combination of genetic and
      environmental factors; however, its pathogenesis remains largely unknown. Here,
      we focus on the endothelial tight-junction protein claudin-5 (CLDN5), because the
      CLDN5 gene is mapped to the schizophrenia-associated 22q11.2 deletion region, and
      a single nucleotide polymorphism in the CLDN5 locus is also linked to
      schizophrenia. We show, by RT-qPCR and immunohistochemistry, that the expressions
      of CLDN5 mRNA and protein are significantly increased and decreased,
      respectively, in the schizophrenic prefrontal cortex (PFC) compared with control
      PFC. These changes were not observed in the schizophrenic visual cortex (VC), and
      neither the density nor diameter of the CD34-positive microvessels was altered in
      the schizophrenic PFC or VC. Interestingly, protein kinase A (PKA) was activated
      in the microvascular and perivascular regions of the schizophrenic PFC, and the
      pPKA-positive microvascular endothelial cells occasionally exhibited focal loss
      of CLND5. Since we previously demonstrated that cAMP induced CLDN5 mRNA
      expression and size-selective loosening of the endothelial barrier in PKA
      independent and -dependent manners, respectively, a similar mechanism could
      contribute to the discrepancy between mRNA and protein expression of CLDN5 in the
      schizophrenic PFC. Taken collectively, these findings provide novel insights into
      the pathophysiology of schizophrenia.

PMID- 29212158
TI  - RNAscope in situ hybridization confirms mRNA integrity in formalin-fixed,
      paraffin-embedded cancer tissue samples.
AB  - Immunohistochemistry remains the overwhelming technique of choice for test
      biomarker evaluation in both clinical or research settings when using formalin
      fixed, paraffin embedded tissue sections. However, validations can be complex
      with significant issues about specificity, sensitivity and reproducibility. The
      vast array of commercially available antibodies from many vendors may also lead
      to non-standard approaches which are difficult to cross-reference. In contrast
      mRNA detection, by in situ hybridization (ISH) with sequence specific probes,
      offers a realistic alternative, with less validation steps and more stringent and
      reproducible assessment criteria. In the present study mRNA ISH was evaluated in
      prospectively and retrospectively collected FFPE samples within a cancer biobank
      setting. Three positive control probes, POLR2A, PPIB and UBC were applied to FFPE
      sections from a range of tumour types in FFPE whole-face (prospective collection)
      or TMA (retrospective collection) formats and evaluated semi-quantitatively and
      by image analysis. Results indicate that mRNA can be robustly evaluated by ISH in
      prospectively and retrospectively collected tissue samples. Furthermore, for 2
      important test biomarkers, PD-L1 and c-MET, we show that mRNA ISH is a technology
      that can be applied with confidence in the majority of tissue samples because
      there are quantifiable levels of control probes indicating overall mRNA
      integrity.

PMID- 29212159
TI  - LEF1, TFE3, and AR are putative diagnostic markers of solid pseudopapillary
      neoplasms.
AB  - The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because
      some SPNs share many similar morphological and immunohistochemical features with
      other pancreatic neoplasms. In this study, we investigated potential diagnostic
      markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA
      microarray and proteome study, we selected six immunohistochemical markers [beta
      catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1),
      transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in
      sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]. We also evaluated the Ki-67
      proliferative index to investigate its associations with prognosis. To validate
      these markers, we studied 91 SPNs as well as 51 pancreatic ductal carcinomas
      (PDC) and 48 neuroendocrine tumors (NET) as controls. We found frequent and
      diffuse nuclear expressions of beta-catenin (98.9%), AR (81.3%), LEF1 (93.4%),
      TFE3 (74.7%), FUS (84.6%), and cytoplasmic expression of WIF-1 (96.7%) in SPNs.
      In contrast, PDCs and NETs showed no expression. (P < 0.001). When beta-catenin,
      LEF1, and TFE3 staining were combined, the sensitivity and specificity were 100%
      and 91.9%, respectively. Four (4.4%) SPNs showed distant metastasis and these
      tumors were associated with a relatively high Ki-67 proliferative index (>= 5%; P
      = 0.013). We identified LEF1, TFE3, and AR as putative diagnostic markers of SPN,
      auxiliary to beta-catenin. Incorporated into an immunohistochemical panel, these
      markers could be beneficial to distinguish SPN from PDC and NET. In addition, we
      suggest that the Ki-67 proliferative index can be a predictive marker of
      metastasis in SPNs.

PMID- 29212160
TI  - Hepatic stroma-educated regulatory DCs suppress CD8+ T cell proliferation in
      mice.
AB  - Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the
      CD4+ T cell response. The present study assessed whether and how liver DCs
      suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated
      with liver stromal cells were characterized by a longer life span, reduced CD11c,
      IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These
      unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells
      to express CD25 and CD69, but inhibited their proliferation. CD8+ T cell
      suppression depended on soluble factors released by LSed-DCs, but not cell-cell
      contact. Compared with mature DCs, LSed-DCs produced more nitric oxide and IL-10.
      Addition of a nitric oxide synthase inhibitor, PBIT, but not an IL-10-blocking
      mAb, reversed LSed-DC inhibition of CD8+ T cell proliferation. We also found that
      LSed-DCs reduced CD8+ T cell-mediated liver damage in a mouse model of autoimmune
      hepatitis. These results demonstrate that the liver stroma induces mature DCs to
      differentiate into regulatory DCs that suppress CD8+ T cell proliferation, and
      thus contribute to liver tolerance.

PMID- 29212161
TI  - Colonization, mortality, and host cytokines response to enterohemorrhagic
      Escherichia coli in rabbits.
AB  - The major virulence factor of enterohemorrhagic Escherichia coli in infections is
      its ability to cause attaching and effacing lesions in enterocytes, as well as to
      produce Shiga toxins. To clarify the pathogenic mechanism and host innate immune
      responses of enterohemorrhagic Escherichia coli in rabbits, experimental
      infections with TS and MY strains were conducted. Among the results, although the
      MY strain's pathogenicity was stronger than the TS, typical symptoms were
      observed in both groups of bacterial-infected rabbits. Pathological changes in
      the heart, liver, and spleen of rabbits infected with the MY strain were more
      severe than those infected with the TS strain, pro-inflammatory cytokines IL
      1beta, IL-6, IL-8, IFN-gamma, and TNF-alpha were induced by both strains, and
      alpha- and beta-defensin were significantly upregulated at 3 d postinfection.
      Moreover, in the spleen, the MY strain induced greater expressions of alpha- and
      beta-defensins than did the TS strain. However, in the liver, the TS strain
      induced greater expressions of alpha- and beta-defensins than did the MY strain.
      Most likely, different replications of the MY and TS strains in the liver and
      spleen induced different host immune responses. Altogether, the findings provide
      new insights into the occurrence and development of enterohemorrhagic Escherichia
      coli-mediated diseases in rabbits.

PMID- 29212162
TI  - Rituximab treatment in adults with refractory minimal change disease or focal
      segmental glomerulosclerosis.
AB  - Rituximab (RTX) may benefit patients with glomerular disease who suffer from
      focal segmental glomerular sclerosis (FSGS) or minimal change disease (MCD).
      Here, we have described our experience treating 6 FSGS and 9 MCD patients with
      steroid-dependent/refractory nephrotic syndrome (NS) with RTX. Patients received
      RTX (375 mg/m2) intravenously on days 1, 8, 23, and 29. During a median follow-up
      of 8 months (range, 3-36 months) after RTX administration, all patients achieved
      complete or partial remission. Relapses decreased by approximately 30-fold
      compared with the year preceding RTX treatment, and an 89.27% reduction in
      proteinuria was observed. Furthermore, RTX treatment could decrease medical costs
      by 76.52% compared with the costs associated with the long-term use (for 12-13
      months) of steroids and immunosuppressive drugs. In conclusion, RTX treatment was
      safe and effective for patients with refractory FSGS or MCD.

PMID- 29212163
TI  - Younger age at surgery and lesser seizure frequency as prognostic factors for
      favorable seizure-related outcome after glioma resection in adults.
AB  - The identification of variables predictive of good seizure control following
      surgical tumor resection in adult glioma patients with tumor-related epilepsy
      would greatly benefit treatment decisions. Therefore, we analyzed the clinical
      data of adult patients with tumor-related epilepsy who underwent tumor resection
      at our institute between November 2011 and August 2013. Patients were divided
      into seizure-free (Engel Ia) and unfavorable outcome groups (Engel Ib-IV), and
      potential prognostic factors were analyzed. Of 90 patients, 61 (68%) had a
      favorable outcome at an average of 3 years after surgery. Our analyses indicated
      that younger age at surgery (P=0.048) and rare seizure frequency (P=0.006) were
      associated with significantly more favorable postoperative seizure-related
      outcomes. In conclusion, younger age at surgery and lesser seizure frequency were
      independent predictors of favorable epileptic seizure control after glioma
      resection in adults. Thus, early surgical resection is necessary for achieving
      favorable seizure outcome.

PMID- 29212164
TI  - Targeted sequencing of established and candidate colorectal cancer genes in the
      Colon Cancer Family Registry Cohort.
AB  - The underlying genetic cause of colorectal cancer (CRC) can be identified for 5
      10% of all cases, while at least 20% of CRC cases are thought to be due to
      inherited genetic factors. Screening for highly penetrant mutations in genes
      associated with Mendelian cancer syndromes using next-generation sequencing (NGS)
      can be prohibitively expensive for studies requiring large samples sizes. The aim
      of the study was to identify rare single nucleotide variants and small indels in
      40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases
      (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from
      the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA
      pooling NGS strategy. We identified 264 variants in 38 genes that were observed
      only in cases, comprising either very rare (minor allele frequency <0.001) or not
      previously reported (n=90, 34%) in reference databases, including six stop-gain,
      three frameshift, and 255 non-synonymous variants predicted to be damaging. We
      found novel germline mutations in established CRC genes MLH1, APC, and POLE, and
      likely pathogenic variants in cancer susceptibility genes BAP1, CDH1, CHEK2, ENG,
      and MSH3. For the candidate CRC genes, we identified likely pathogenic variants
      in the helicase domain of POLQ and in the LRIG1, SH2B3, and NOS1 genes and
      present their clinicopathological characteristics. Using a DNA pooling NGS
      strategy, we identified novel germline mutations in established CRC
      susceptibility genes in familial CRC cases. Further studies are required to
      support the role of POLQ, LRIG1, SH2B3 and NOS1 as CRC susceptibility genes.

PMID- 29212165
TI  - Assessment of pancreatic neuroendocrine tumor cytologic genotype diversity to
      guide personalized medicine using a custom gastroenteropancreatic next-generation
      sequencing panel.
AB  - Background: Recent genetic studies have highlighted that alterations in MEN1,
      chromatin remodeling genes, and mammalian target of rapamycin (mTOR) pathway
      genes are the most frequent molecular events identified in pancreas
      neuroendocrine tumors (pNETs). The prognostic or predictive impact of these
      biomarkers and other less frequently observed aberrations, i.e. PTEN, TSC2 and
      PIK3CA are relatively unknown. The aims of this targeted next generation
      sequencing (NGS) study were to assess tumor cytology genotype diversity, to
      survey for potential adverse prognostic biomarkers and the prevalence of mTOR
      pathway variants. Methods: Using a custom 15 gene gastroenteropancreatic
      neuroendocrine tumor panel, targeted NGS of archived (2002-2013) primary pNETs
      (n=90) and pNET liver metastasis (n=32) cytology smears was performed. Results:
      The genetic variant landscape revealed that 21% and 28% of primary and metastatic
      liver pNETs harbored >= 2 variants per tumor, respectively. The most prevalent
      primary tumor variants were in the MEN1 (42%), DAXX (11%), ATRX (10%), and TSC2
      (8%) genes. Patients harboring aberrations in TSC2, KRAS or TP53 were more likely
      to experience disease progression and reduced overall survival, when compared to
      individuals who were wild-type. The prevalence of these potential prognostic
      biomarkers in early disease was observed in 3.3% of the primary tumor cohort.
      mTOR pathway variants including alterations in PTEN, TSC2 and PIK3CA were
      identified in 10% and 12.5% of primary tumors and pNET liver metastasis,
      respectively. Conclusion: Cytology based tumor genotyping revealed a broad
      spectrum of genetic variants including possible adverse prognostic biomarkers,
      reflective of an aggressive phenotype. It also demonstrated the prevalence of
      potential predictive biomarkers for mTOR pathway inhibitor sensitivity.

PMID- 29212166
TI  - Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through
      regulation of the PI3K-Akt-mTOR signaling pathway.
AB  - The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has
      been recently shown to be dysregulated during disease occurrence and to play an
      important role in the progression of several cancers. However, the biological
      role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric
      cancer remain unclear. In the present study, we found that UCA1 was aberrantly
      upregulated in gastric cancer tissues and gastric cancer cell lines, and was
      associated with TNM stage and metastasis. UCA1 silencing significantly inhibited
      gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also
      found that UCA1 played an important role in the migration and invasion of gastric
      cancer cells in vitro and in vivo. The molecular mechanism of UCA1 suggested that
      UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream
      mediators, to alter gastric cancer progression in vitro and in vivo.
      Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of
      gastric cancer. In addition, the study characterized a novel lncRNA-mRNA
      regulatory network, which may lead to a better understanding of the pathogenesis
      of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this
      malignancy.

PMID- 29212167
TI  - A nomogram to predict HER2 status in breast cancer patients with HER2-borderline
      disease as determined via immunohistochemistry.
AB  - This study aimed to develop a nomogram to predict fluorescence in situ
      hybridization (FISH) assay results for HER2-borderline breast cancer as
      determined via immunohistochemistry (IHC) among patients in China. We reviewed a
      database of breast cancer patients diagnosed between January 2007 and April 2013
      at our institutions. We used logistic regression to develop a nomogram and we
      used receiver operating characteristic curve analysis and calibration plots to
      validate our nomogram. In total, 1138, 301 and 344 patients had IHC-determined
      HER2-negative, HER2-borderline and HER2-positive disease, respectively. Within
      the training cohort, univariate and multivariate analyses suggested that estrogen
      receptor (ER) status, progesterone receptor (PR) status and tumor grade were
      significantly associated with HER2 status (P<0.01). A nomogram was developed and
      the AUCs for the training and validation cohorts were 0.795 and 0.749,
      respectively. The calibration plots suggested that the model was well calibrated.
      This new nomogram can be used to predict HER2 status in HER2-borderline breast
      cancer patients and will be particularly helpful to resource-limited countries.

PMID- 29212168
TI  - Nrf2 induces cisplatin resistance via suppressing the iron export related gene
      SLC40A1 in ovarian cancer cells.
AB  - Induction of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) has been
      demonstrated to be involved in cisplatin resistance in ovarian cancer. Solute
      carrier family 40 member 1 (SLC40A1) is an iron exporter, which possesses many
      putative Nrf2 binding sites. Here we hypothesize that it may be a possible
      downstream gene of Nrf2. Elevated level of Nrf2 and reduced level of SLC40A1 were
      found in cisplatin-resistant ovarian cancer cells as compared with cisplatin
      sensitive ovarian cancer cells. Exogenous knockdown of Nrf2 leaded to increased
      expression of SLC40A1. While overexpression of Nrf2 resulted in decreased
      expression of SLC40A1. Chromatin immunoprecipitation (ChIP) and dual-luciferase
      reporter assay revealed that Nrf2 inhibited the transcription of SLC40A1.
      Overexpression of SLC40A1 was able to reverse cisplatin resistance induced by
      Nrf2, while knockdown of SLC40A1 restored cisplatin resistance and increased iron
      concentration. Desferal, an iron chelator, was found to overcome cisplatin
      resistance through iron deprivation. Its function was boosted when combined with
      brusatol, an Nrf2 inhibitor. Taken together, this study first demonstrated that
      Nrf2 could transcriptionally suppress the expression of SLC40A1. Iron overload
      induced by SLC40A1 resulted in cisplatin resistance in ovarian cancer. Targeting
      iron metabolism may be a new therapeutic strategy to reverse drug resistance in
      ovarian cancer treatment.

PMID- 29212169
TI  - CCCTC-binding factor inhibits breast cancer cell proliferation and metastasis via
      inactivation of the nuclear factor-kappaB pathway.
AB  - CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in
      multiple cellular processes, including growth, proliferation, differentiation,
      and apoptosis. Although CTCF deletion or mutation has been associated with human
      breast cancer, the role of CTCF in breast cancer is questionable. We investigated
      the biological functions of CTCF in breast cancer and the underlying mechanism.
      The results showed that CTCF expression in human breast cancer cells and tissues
      was significantly lower than that in normal breast cells and tissues. In
      addition, CTCF expression correlated significantly with cancer stage (P = 0.043)
      and pathological differentiation (P = 0.029). Furthermore, CTCF overexpression
      resulted in the inhibition of proliferation, migration, and invasion, while CTCF
      knockdown induced these processes in breast cancer cells. Transcriptome analysis
      and further experimental confirmation in MDA-MD-231 cells revealed that forced
      overexpression of CTCF might attenuate the DNA-binding ability of nuclear factor
      kappaB (NF-kappaB) p65 subunit and inhibit activation of NF-kappaB and its target
      pro-oncogenes (tumor necrosis factor alpha-induced protein 3 [TNFAIP3]) and genes
      for growth-related proteins (early growth response protein 1 [EGR1] and growth
      arrest and DNA-damage-inducible alpha [GADD45a]). The present study provides a
      new insight into the tumor suppressor roles of CTCF in breast cancer development
      and suggests that the CTCF/NF-kappaB pathway is a potential target for breast
      cancer therapy.

PMID- 29212170
TI  - Leptin receptor signaling via Janus kinase 2/Signal transducer and activator of
      transcription 3 impacts on ovarian cancer cell phenotypes.
AB  - Ovarian cancer is a leading cause of cancer mortality in women world-wide.
      Considerable progress has been made to characterize the different subtypes of
      ovarian cancer, but specific therapies remain limited and prognosis poor.
      Cytokine signaling via the interleukin-6 receptor (IL-6R) family and related
      receptors has been implicated in a number of cancers, including those with an
      ovarian origin. The leptin receptor (LEPR) is structurally related to these
      receptors and utilizes similar downstream pathways. LEPR has diverse roles in
      metabolism, appetite and bone formation with obesity linked to both elevated
      levels of leptin and increased cancer incidence. This study investigated a
      potential role for LEPR signaling in ovarian cancer. Leptin stimulation led to
      increased proliferation, survival and migration of LEPR-expressing ovarian cancer
      cell lines, with the effects shown to be mediated by the downstream Janus kinase
      2/Signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. A
      significant correlation was identified between high co-expression of leptin and
      LEPR and decreased patient survival. This study collectively suggests that
      leptin/LEPR signaling via JAK2/STAT3 has the potential to significantly impact on
      pathogenesis in a subset of ovarian cancer patients who may benefit from
      strategies that dampen this pathway.

PMID- 29212171
TI  - Clinical outcomes and prognostic factors of stereotactic body radiation therapy
      for intrahepatic cholangiocarcinoma.
AB  - Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive
      treatment modality for patients with intrahepatic cholangiocarcinoma (ICC) when
      surgical treatment cannot be applied. The CyberKnife(r) is a SBRT system that
      allows for real-time tracking of the tumor. The purpose of this study was to
      evaluate the clinical outcomes and prognostic factors for ICC patients receiving
      this treatment. Twenty-eight patients with ICC were enrolled in the present
      study. The median prescription dose was 45 Gy (range, 36-54 Gy), fractionated 3
      to 5 times with a 70% to 92% isodose line. Local control, overall survival,
      progression-free survival and toxicity were studied. The median follow-up time
      was 16 months (3-42 months). Based on modified Response Evaluation and Criteria
      in Solid Tumors (mRECIST), response rate and disease control rate of SBRT in ICC
      were 46.4% (13/28) and 89.3% (25/28), respectively. Median overall survival was
      15 months (95% CI, 7.22-22.78). 1- and 2-years survival rates were 57.1% and
      32.1%, and 1- and 2- years Progression-free Survival rates were 50.0 % and 21.4
      %. Multivariate analysis revealed that number of lesions (solitary vs. multiple
      nodules), CA19-9 levels (<=37 U/mL vs. 37-600/>600) and TNM stage (AJCC stage)
      were independent prognostic factors for ICC patients treated with SBRT. Toxicity
      was mostly transient and tolerable. No greater than grade 3 toxicity was
      observed. These results suggested that CyberKnife SBRT might be a good
      alternative treatment for unresectable ICC.

PMID- 29212172
TI  - Safflor yellow B reduces hypoxia-mediated vasoconstriction by regulating
      endothelial micro ribonucleic acid/nitric oxide synthase signaling.
AB  - Hypoxia-induced generation of vasoconstrictors reduces cerebral blood flow (CBF)
      while nitric oxide (NO) synthase (NOS) and microRNAs (miRNA) in endothelial cells
      (ECs) suppress vasoconstriction. Safflor yellow B (SYB), a natural plant
      compound, previously attenuated angiotensin II-mediated injury of ECs and
      maintained endothelial function. This study investigated the putative involvement
      of NOS and miRNAs in SYB-mediated resistance to hypoxia-induced vasoconstriction.
      In vivo, chronic hypoxia was induced in rats, and SYB was administered
      intravenously. In vitro, rat primary aortic ECs were cultured under oxygen and
      glucose deprivation. After treatment with anti-microR-199a, as well as the NOS
      inhibitor, N(G)-nitro-L-arginine methyl ester, SYB, or both, cell viability, NO
      and peroxynitrite (ONOO-) levels, NOS expression, and miRNA levels were
      evaluated. SYB significantly alleviated hypoxia-mediated vasoconstriction and
      increased CBF endothelium-dependently. SYB upregulated miR-199a, increased EC
      viability, decreased endothelin-1 (ET-1) levels, inhibited protein kinase C (PKC)
      activity, and suppressed hypoxia inducible factor-1alpha (HIF-1alpha) expression.
      Furthermore, the SYB-mediated reduction of inducible NOS reduced ONOO- levels. In
      addition, SYB downregulated miR-138 and, thereby, enhanced S100A1 and endothelial
      NOS activity. Hypoxia-mediated regulation of miR-138 and miR-199a inhibited
      endothelial NOS expression and activation, which triggered ET-1 release and
      vasoconstriction. Therefore, SYB treatment reduced hypoxia-induced
      vasoconstriction through miR-199a/endothelial NOS signaling.

PMID- 29212173
TI  - Comprehensive genomic sequencing detects important genetic differences between
      right-sided and left-sided colorectal cancer.
AB  - Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found
      to be more effective against left-sided colorectal cancer (LCRC) than right-sided
      colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor
      genetic alterations associated with resistance to anti-EGFR therapy and tested
      this using comprehensive genomic sequencing. Materials and methods: A total of
      201 patients with either primary RCRC or LCRC were analyzed. We investigated
      tumors for genetic alterations using a 415-gene panel, which included alterations
      associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR,
      FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K
      pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12
      genes, theoretically considered to respond to anti-EGFR therapy, were defined as
      "all wild-type", while remaining patients were defined as "mutant-type". Results:
      Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively.
      Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56
      patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients
      (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR
      therapy, RCRC showed significantly worse progression-free survival (PFS) than
      LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared
      with "all wild-type" LCRC (P = 0.004). Conclusions: RCRC is more likely to harbor
      genetic alterations associated with resistance to anti-EGFR therapy compared with
      LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the
      non-random distribution of genetic alterations in CRC.

PMID- 29212174
TI  - Melatonin attenuates hypoxia-induced epithelial-mesenchymal transition and cell
      aggressive via Smad7/ CCL20 in glioma.
AB  - Tumor recurrence in gliomas is partly attributed to increased epithelial
      mesenchymal transition (EMT) and enhanced tumor cell dissemination in the
      adjacent brain parenchyma. Thus, exploring effective strategies for against EMT
      like changes in glioma invasion and recurrence will be important for glioma
      treatment. In this study, we investigated the roles of melatonin in hypoxia
      induced EMT suppression, and found that melatonin could significantly suppress
      the release of the cytokine, CCL20, from cancer cells and antagonize glioma cell
      metastasis and invasion under hypoxic stress in glioma cells. Furthermore, our
      findings show that melatonin deregulates Smad7 expression to suppress
      TGFbeta/Smad-mediated increase in CCL20 transcript levels and CCL20-induced EMT
      occurrence, suggesting a potential anti-EMT therapeutic role for melatonin in
      malignant transformation in gliomas.

PMID- 29212175
TI  - The role of established East Asian obesity-related loci on pediatric leptin
      levels highlights a neuronal influence on body weight regulation in Chinese
      children and adolescents: the BCAMS study.
AB  - Genome-wide association studies have identified multiple variants associated with
      adult obesity, mostly in European-ancestry populations. We aimed to
      systematically assess the contribution of key loci, which had been previously
      shown to be associated in East Asian adults, to childhood obesity, related
      adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve
      single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five
      adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and
      retinol binding protein 4) were evaluated in 3,506 Chinese children and
      adolescents aged 6-18. After correction for multiple comparisons, six of these
      SNPs were robustly associated with childhood obesity: FTO-rs1558902 (P=5.6*10-5),
      MC4R-rs2331841 (P=4.4*10-4), GNPDA2-rs16858082 (P = 3.4*10-4), PCSK1-rs261967 (P
      = 0.001), SEC16B-rs516636 (P = 0.004) and MAP2K5-rs4776970 (P = 0.004), with odds
      ratios ranging from 1.211 to 1.421; while ITIH4-rs2535633 and BDNF-rs2030323
      yielded nominal association with the same trait (P < 0.05). Moreover, the risk
      alleles of six SNPs displayed significant (P < 0.004) or nominal (P < 0.05)
      association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5,
      GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association
      with increased leptin levels (P = 6.2*10-11). Our results reveal that key obesity
      associated loci previously reported in Europeans, but also associated with East
      Asian adults, are also associated with obesity and/or metabolic quantitative
      traits in Chinese children. These associations coincide with six brain-expressed
      loci that correlate with leptin levels, thus may point to an important neuronal
      influence on body weight regulation in the pediatric setting.

PMID- 29212176
TI  - Silencing of lncRNA AFAP1-AS1 suppressed lung cancer development by regulatory
      mechanism in cis and trans.
AB  - Although the long noncoding RNA AFAP1-AS1 has been shown to be involved in
      various types of cancer, its involvement in lung cancer remains poorly
      understood. In the current study, we found that AFAP1-AS1 was substantially over
      expressed in lung cancer tissues and cell lines. In addition, AFAP1-AS1
      expression level was proven to be associated with the malignant features of lung
      cancer. Knockdown of AFAP1-AS1 significantly suppressed cell proliferation by
      increasing cell apoptosis and G0/G1 phase retardation of cell cycle in lung
      cancer cells. Furthermore, AFAP1-AS1 knockdown could suppress tumor growth of
      lung cancer in BALB/c nude mice. We also identified that AFAP1-AS1 silencing
      could influence the expression of AFAP1 and KRT1 on mRNA and protein level by cis
      and trans regulatory mechanism. Moreover, the oncogenic activities of AFAP1-AS1
      on cell proliferation are partially mediated by KRT1. In summary, these findings
      demonstrate that AFAP1-AS1 plays an essential role in promoting lung cancer
      development in vitro and vivo. It indicated that AFAP1-AS1 is a promising
      prognostic predictor for patients with lung cancer.

PMID- 29212177
TI  - Differences in brain gray matter volume in patients with Crohn's disease with and
      without abdominal pain.
AB  - Increasing evidence indicates that abnormal pain processing is present in the
      central nervous system of patients with Crohn's disease (CD). The purposes of
      this study were to assess changes in gray matter (GM) volumes in CD patients in
      remission and to correlate structural changes in the brain with abdominal pain.
      We used a 3.0 T magnetic resonance scanner to examine the GM structures in 21 CD
      patients with abdominal pain, 26 CD patients without abdominal pain, and 30
      healthy control subjects (HCs). Voxel-based morphometric analyses were used to
      assess the brain GM volumes. Patients with abdominal pain exhibited higher CD
      activity index and lower inflammatory bowel disease questionnaire scores than
      those of the patients without abdominal pain. Compare to HCs and to patients
      without abdominal pain, patients with abdominal pain exhibited lower GM volumes
      in the insula and anterior cingulate cortex (ACC); whereas compare to HCs and to
      patients with abdominal pain, the patients without abdominal pain exhibited
      higher GM volumes in the hippocampal and parahippocampal cortex. The GM volumes
      in the insula and ACC were significantly negatively correlated with daily pain
      scores. These results suggest that differences exist in the brain GM volume
      between CD patients in remission with and without abdominal pain. The negative
      correlation between the GM volumes in the insula and ACC and the presence and
      severity of abdominal pain in CD suggests these structures are closely related to
      visceral pain processing.

PMID- 29212178
TI  - A retrospective comparative study of progression-free survival and overall
      survival between metachronous and synchronous metastatic renal cell carcinoma in
      intermediate- or poor-risk patients treated with VEGF-targeted therapy.
AB  - Introduction: The aim of this study was to compare progression-free survival
      (PFS) and overall survival (OS) between metachronous and synchronous metastatic
      renal cell carcinomas treated with VEGF-targeted therapy. Methods: Between 2005
      and 2014, 93 (78.8%) intermediate- and 25 (21.2%) poor-Heng-risk patients,
      including 32 (27.1%) patients with metachronous and 86 (72.9%) patients with
      synchronous renal cell carcinoma, were enrolled retrospectively. PFS and OS
      values were compared according to the number of risk factors and treatment-free
      interval using the Kaplan-Meier method and log-rank test. The prognostic risk
      factors were also evaluated using a Cox proportional hazard model, with a p-value
      < 0.05 indicating statistical significance. Results: During a median 5.0-month
      treatment and 59.3-month follow-up, analysis of the PFS/OS of SM (5.2/9.6 months)
      and MM (9.6/20.1 months) yielded a significant difference in OS (p = 0.010).
      However, there was no significant difference when Heng risk groups and treatment
      free interval were considered (p > 0.05). There was a significant difference in
      PFS (hazard ratio: 1.81) and OS (hazard ratio: 2.19) with increasing number of
      Heng risk factors among patients with synchronous renal cell carcinoma and a
      treatment-free interval <1 year. Metastatic type, anemia, and neutrophilia were
      significant predictive factors for OS in multivariable analysis (p < 0.05).
      Conclusion: The metastatic type of renal cell carcinoma (synchronous or
      metachronous) significantly affects survival; metachronous type is associated
      with more favorable outcomes than synchronous type. However, after stratification
      according to Heng risk factors and treatment-free interval, the differences in
      survival between metachronous and synchronous type were insignificant.

PMID- 29212179
TI  - Impact of cavitron ultrasonic surgical aspirator (CUSA) and bipolar
      radiofrequency device (Habib-4X) based hepatectomy for hepatocellular carcinoma
      on tumour recurrence and disease-free survival.
AB  - Background: The aim of this study was to evaluate the oncological outcomes of
      hepatocellular carcinoma patients undergoing liver resection using cavitron
      ultrasonic surgical aspirator (CUSA) or radiofrequency (RF) based device Habib
      4X.?. Study Design: We prospectively analyzed the data of 280 patients who
      underwent liver resection for hepatocellular carcinoma at our institution from
      2010-2012 with follow up till August 2016. The CUSA was used in the 163 patients
      whilst Habib-4X in 117 patients. The end points of analysis were oncological
      outcomes as disease recurrence, disease-free survival (DFS) and overall survival
      (OS) were estimated by the Kaplan-Meier method, which has been compared with all
      other existing literature on the survival study. Results: Compared with CUSA the
      reported incidence of recurrence was significantly lower, in Habib-4X group; p <
      0.01. The median DFS was significantly better in Habib-4X group than CUSA group
      (50.80 vs 45.87 months, p = 0.03). The median OS was better in Habib-4X group
      than CUSA group (60.57 vs 57.17 months, p = 0.12) though the lesser difference in
      OS between the groups might be explained by the use of palliative therapies as
      TACE, percutaneous RFA, etc. in case of recurrence. Conclusions: RF based device
      Habib-4X, is safe and effective device for resection of hepatocellular carcinoma,
      in comparison to CUSA with better oncological outcomes, i.e., significantly
      lesser tumour recurrence and better DFS. This could be explained on the basis of
      systemic and local immunomodulatory effect involving induction of kupffer cells
      and effector CD-8 T cells that help in minimizing postoperative complications and
      bring more advantageous oncological outcomes.

PMID- 29212180
TI  - PADI4 rs2240337 G>A polymorphism is associated with susceptibility of esophageal
      squamous cell carcinoma in a Chinese population.
AB  - Background: Esophageal cancer (EC) remains one of the major causes of cancer
      incidence and mortality worldwide. Genetic factors, such as single nucleotide
      polymorphisms (SNPs), may contribute to the carcinogenesis of EC. Methods: We
      conducted a hospital based case-control study to evaluate the genetic
      susceptibility of SNPs on the development of EC. A total of 629 esophageal
      squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this
      study. Seven PADI4 SNPs were determined by ligation detection reaction method.
      Results: Our findings suggested that the PADI4 rs2240337 GA/AA variants were
      significantly associated with decreased risk of ESCC. Haplotype PADI4
      Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and
      Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562
      polymorphism was correlated with decreased susceptibility to ESCC, while
      Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was
      correlated with increased susceptibility of ESCC. Stratification analyses
      demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366
      AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype.
      Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT,
      rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years),
      rs11203366 AA genotype was associated with increased risk of ESCC. PADI4
      rs1886302 CC variant was associated with ESCC susceptibility in female cohort.
      Conclusions: Our study suggested that PADI4 rs2240337 G>A polymorphism may be
      correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302,
      rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered
      susceptibility of ESCC based on sex, age, smoking status and alcohol consumption.
      However, larger studies among different ethnic populations and further
      experiments using genetically mutated cells or animals are warranted to verify
      our conclusion.

PMID- 29212181
TI  - Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes lung
      tumorigenesis via attenuating p53 stability.
AB  - Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3/IMP3/KOC), initially
      identified as an RNA-binding protein, is highly expressed in embryonic tissues
      and a variety of cancers. Previously, our group reported that IGF2BP3 may serve
      as a potential diagnostic marker for lung cancer. However, little is known about
      the function of IGF2BP3 in lung cancer development. Here we demonstrate that
      IGF2BP3 expression was markedly increased in lung cancer tissues compared to
      normal tissues at both mRNA and protein levels. Overexpression of IGF2BP3 in lung
      cancer cells promoted cell proliferation, tumor migration and invasion in vitro
      and in vivo, whereas knockdown of IGF2BP3 exhibited opposite effects. Notably
      IGF2BP3 was directly associated with a deubiquitinase Ubiquitin specific
      peptidase 10 (USP10) and attenuated its function in stabilizing p53 protein.
      Silencing IGF2BP3 expression in lung cancer cells consistently increased the half
      life and protein level of p53 and induced G0/G1 arrest. Thus, our data together
      demonstrate that IGF2BP3 promotes lung tumorigenesis via attenuating p53 protein
      stability.

PMID- 29212182
TI  - Oncogenic p95HER2/611CTF primes human breast epithelial cells for metabolic
      stress-induced down-regulation of FLIP and activation of TRAIL-R/Caspase-8
      dependent apoptosis.
AB  - Oncogenic transformation triggers reprogramming of cell metabolism, as part of
      the tumorigenic process. However, metabolic reprogramming may also increase the
      sensitivity of transformed cells to microenvironmental stress, at the early
      stages of tumor development. Herein, we show that transformation of human breast
      epithelial cells by the p95HER2/611CTF oncogene markedly sensitizes these cells
      to metabolic stress induced by the simultaneous inhibition of glucose and
      glutamine metabolism. In p95HER2/611CTF-transformed cells, metabolic stress
      activates a TNF related apoptosis-inducing ligand (TRAIL)-R and caspase-8
      dependent apoptotic process that requires prior down-regulation of cellular FLICE
      like inhibitor protein (c-FLIP) levels. Importantly, sustained mTOR activation is
      involved in FLIP down-regulation and apoptosis induced by metabolic stress. In
      vivo experiments in immunodeficient mice demonstrate a requirement for caspase-8
      in restraining primary tumor growth of xenografts with p95HER2/611CTF-transformed
      cells. Collectively, these data define a critical role of the extrinsic pathway
      of apoptosis in the control of tumor initiation by microenvironmental cues.

PMID- 29212183
TI  - Role of IL-17 in LPS-induced acute lung injury: an in vivo study.
AB  - To assess the clinical significance of IL-17 in patients with sepsis-induced
      acute respiratory distress syndrome (ARDS) and to investigate the effects of IL
      17 blocking in a mouse model of acute lung injury (ALI). Significantly increased
      IL-17 level was found in patients with sepsis-related ARDS compared to healthy
      controls, whereas significantly increased plasma IL-17 level was also observed in
      non-survivors compared to that in survivors. According to the data from the mouse
      ALI model, we found significantly increased IL-17 level in lung tissue lysates,
      mouse bronchoalveolar lavage fluid (mBALF) and plasma at 6, 12 and 24 h after
      ALI. Histological analyses revealed that reduced sign of pathological changes and
      lung injury score in the lungs at 48 h after IL-17 blocking antibody
      administration. Reduced level of proinflammatory tumor necrosis factor alpha and
      increased level of anti-inflammatory factor interleukin-10 were found in both
      mBALF and plasma. Moreover, IL-17 blocking antibody administration attenuated the
      expression of RORgammat and activity of PI3K-Akt pathway. Increased IL-17 was
      presented in patients with sepsis-induced ARDS and IL-17 may serve as a biomarker
      to indicate the severity of ARDS. Moreover, IL-17 antibody administration could
      relieve the ALI symptom by affecting RORgammat level and PI3K pathway.

PMID- 29212184
TI  - Cordycepin and a preparation from Cordyceps militaris inhibit malignant
      transformation and proliferation by decreasing EGFR and IL-17RA signaling in a
      murine oral cancer model.
AB  - Cordyceps militaris (CM) and its active ingredient cordycepin have been reported
      to inhibit tumor growth, but the mechanisms are not fully understood. This study
      used a mouse model for oral cancer and a cell line, 4NAOC-1 derived from the
      model to study the mechanisms. Our results show that a CM preparation (CMP) can
      significantly inhibit tumor development and malignant transformation in the
      model. In vitro data indicate that CMP and cordycepin can inhibit 4NAOC-1 cell
      proliferation, either anchorage-dependent or -independent. Cordycepin can also
      increase cell apoptosis, and decrease cell mitosis and EGFR signaling. In
      accordance, CMP treatment can significantly decrease the levels of ki-67 and EGFR
      signaling molecules in cancer tissues. We also found that the levels of IL-17A in
      cancer tissues of control mice were significantly increased, and CMP inhibited
      these levels. IL-17A can stimulate cancer cell proliferation, which can be
      suppressed by cordycepin. Furthermore, cordycepin can reduce the expression of IL
      17RA and its downstream signaling molecules. Moreover, CMP and cordycepin can
      significantly decrease IL-17A production in vitro and in vivo. Finally, CMP and
      its ingredients can enhance tumoricidal activities with increase in IFN-gamma and
      TNFalpha, and decrease PD-L1 expression. In conclusion, CMP and its ingredient
      cordycepin can inhibit tumor growth and malignant transformation in a mouse model
      for oral cancer via inhibition of EGFR- and IL-17RA-signaling and enhancement of
      anti-tumor immunity.

PMID- 29212185
TI  - Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis
      in malignant pleural mesothelioma.
AB  - Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes
      associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding
      motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid
      mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in
      various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might
      affect the progression of mesothelioma by stimulating cell migration and invasion
      through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown,
      and conversely increased by forced expression of the active form of YAP1,
      suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and
      invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA
      treatment increased cell motility and invasion, and this was abolished by RHAMM
      knockdown, suggesting that HA may augment local progression of MPM cells via
      RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM
      transcription by modulating YAP1/TAZ activity, decreased the motility and
      invasion of MPM cells. Collectively, these data suggest that HA is an
      "unfavorable" factor because it promotes malignancy in mesothelioma and that the
      YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for
      inhibition of disease progression in MPM.

PMID- 29212186
TI  - alpha7 nAChR mediated Fas demethylation contributes to prenatal nicotine exposure
      induced programmed thymocyte apoptosis in mice.
AB  - This study aimed to investigate the effects of prenatal nicotine exposure (PNE)
      on thymocyte apoptosis and postnatal immune impairments in vivo and further
      explore the epigenetic mechanisms of the pro-apoptotic effect of nicotine in
      vitro. The results showed that PNE caused immune impairments in offspring on
      postnatal day 49, manifested as increased IL-4 production and an increased
      IgG1/IgG2a ratio in serum. Enhanced apoptosis of total and CD4+SP thymocytes was
      observed both in fetus and in offspring. Further, by exposing thymocytes to 0-100
      MUM of nicotine in vitro for 48 h, we found that nicotine increased alpha7
      nicotinic acetylcholine receptor (nAChR) expression, activated the Fas apoptotic
      pathway, and promoted thymocyte apoptosis in concentration-dependent manners. In
      addition, nicotine could induce Tet methylcytosine dioxygenase (TET) 2 expression
      and Fas promoter demethylation, which can be abolished by TET2 siRNA
      transfection. Moreover, the alpha7 nAChR specific antagonist alpha-bungarotoxin
      can abrogate nicotine-induced TET2 increase, and the following Fas demethylation
      and Fas-mediated apoptosis. In conclusion, our findings showed, for the first
      time, that alpha7 nAChR activation could induce TET2-mediated Fas demethylation
      in thymocytes and results in the upregulation of Fas apoptotic pathway, which
      provide evidence for elucidating the PNE-induced programmed thymocyte apoptosis.

PMID- 29212187
TI  - Autophagy protein LC3 regulates the fibrosis of hypertrophic scar by controlling
      Bcl-xL in dermal fibroblasts.
AB  - Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by
      excessive hypercellularity and extracellular matrix (ECM) component deposition.
      Autophagy is a tightly regulated physiological process essential for cellular
      maintenance, differentiation, development and homeostasis. However, during the
      formation of HS, whether and how autophagy is regulated in dermal fibroblasts are
      still far from elucidated. Here we detected the autophagic capacity in HS and
      normal skin (NS) counterparts, explored and verified the key regulatory molecules
      of autophagy in HS-derived fibroblasts (HSFs), and validated the data using
      rabbit ear scar model. Transmission electron microscopy (TEM) and immunostaining
      data showed that LC3-positive cells and autophagosomes in HS/HSFs were more
      intensive relative to those in NS/NSFs groups. Knockdown of LC3 (shLC3) could
      significantly block the expressionof type I collagen (Col 1, p < 0.01) and type
      III collagen (Col 3, p < 0.01) and thus inhibit the fibrosis of HSFs. shLC3
      resistant to autophagy was shown to be Bcl-xL-, not Bcl-2-dependent, and
      silencing of Bcl-xL (sibcl-xL) significantly increased apoptosis of HSFs (p <
      0.01). Immunofluorescence results showed that instead of inhibiting alpha-SMA
      protein expression, shLC3 could change its architecture arrangement in HSFs.
      sibcl-xL showed that Bcl-xL was a key signaling molecule involved in HSFs
      autophagy. More importantly, both shLC3 and sibcl-xL obviously improved the
      appearance and architecture of the rabbit ear scar, and reduced scar formation on
      the rabbit ear. Therefore, the aberration of LC3 protein processing compromised
      autophagy in HS might associate with its pathogenesis in wound repair. LC3
      regulated HS fibrosis by controlling the expression of Bcl-xL in HSFs. Thus, Bcl
      xL might serve as a potential molecular target, providing a novel strategy for HS
      therapy.

PMID- 29212188
TI  - Baseline platelet parameters for predicting early platelet response and clinical
      outcomes in patients with non-cardioembolic ischemic stroke treated with
      clopidogrel.
AB  - Purpose: The present study investigated whether routine baseline platelet
      parameters(BPPs) detected before clopidogrel therapy in acute non-cardioembolic
      ischemic stroke(NCIS) could predict early platelet response and future clinical
      outcomes. Results: The CYP2C19 polymorphisms constituted independent risk factors
      for LCR. The number of female patients, the incidence of diabetes mellitus (DM),
      the level of low-density lipoprotein(LDL) cholesterol, and the neutrophil-to
      lymphocyte ratio(NLR) were significantly high in the clinical clopidogrel
      resistance (CCR) group. However, none of the BPPs had a significant association
      with laboratory clopidogrel resistance (LCR) or discriminated with the cut-off
      values regarding LCR or CCR. The patients were divided into two groups according
      to the average mean platelet volume(MPV) or platelet count(PC). We found that the
      HbA1c level, the number of female patients, and the CCR were higher in the groups
      with elevated MPV (>= 10.6fL) and PC (>= 235 * 109/L); the LCR, the NIHSS score
      at discharge, and elevated MPV and PC were risk predictors for CCR. Materials and
      Methods: This study included 196 patients with acute NCIS who underwent routine
      blood tests upon admission, were treated with clopidogrel, and were followed up
      for 6 months. Early platelet response was assessed and the CYP2C19 genetic
      variants were screened for. All participants were categorized into either
      laboratory clopidogrel resistance(LCR) or clinical clopidogrel resistance (CCR)
      groups. Conclusions: Elevated baseline MPV and PC before clopidogrel therapy, as
      well as CYP2C19 gene variants, should be included in a risk algorithm for NCIS.
      Furthermore, other nongenetic clinical risk factors should be assessed for
      optimal prediction of the risk for thrombotic events because of individual
      variability in platelet response to clopidogrel.

PMID- 29212189
TI  - Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in
      vivo studies.
AB  - Previous reports have shown that some tyrosine kinase inhibitors (TKIs) could
      inhibit the ATP-binding cassette (ABC) transporters involved in multidrug
      resistance (MDR). Quizartinib (AC220), a potent class III receptor tyrosine
      kinase inhibitor (TKI), was synthesized to selectively inhibit FMS-like tyrosine
      kinase-3 (FLT3), a target in the treatment of acute myeloid leukemia (AML).
      Quizartinib is currently under clinical trials for FLT3 ITD and wild-type AML and
      is tested in combination with chemotherapy. While non-toxic to cell lines,
      quizartinib at 3 MUM showed significant reversal effect on wild-type and mutant
      ABCG2 (R482T)-mediated MDR, and only a moderate reversal effect on mutant ABCG2
      (R482G)-mediated MDR. Results also showed that quizartinib reversed MDR not by
      reducing the expression of ABCG2 protein, but by antagonizing the drug efflux
      function and increasing the intracellular accumulation of substrate anticancer
      drugs in ABCG2-overexpressing cells. Importantly, quizartinib at 30 mg/kg
      strongly enhanced the effect of topotecan (3 mg/kg) in ABCG2-overexpressing
      (H460/MX20) xenografts in athymic nude mice. These results demonstrated that
      quizartinib potentiates the antineoplastic activity of wild-type and R482T mutant
      ABCG2 substrates. These findings may be useful in clinical practice for cancer
      combination therapy with quizartinib.

PMID- 29212190
TI  - Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy.
AB  - Poor water-solubility of artesunate (ARS) hampers its clinical application. We
      here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain
      ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and
      dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen
      species (ROS) and peroxynitrite (ONOO?) generations. Although nGO-PEG with near
      infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect
      of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO?
      generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect
      of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20
      tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO? scavenger)
      instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly
      blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation,
      demonstrating that ONOO? instead of ROS dominated the synergistic chemo
      photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation
      resulted in a complete tumor cure within 15 days earlier than other treatment
      groups, and did not induce apparent histological lesion for the mice treated with
      nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the
      synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively,
      nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer
      therapy.

PMID- 29212191
TI  - Incidence and risk of hematologic toxicities in cancer patients treated with
      regorafenib.
AB  - Regorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase
      inhibitor, has been approved for the treatment of several malignancies. As a non
      traditional cytotoxic chemotherapeutic agent, regorafenib is often associated
      with hematologic toxicities. Here we searched PubMed and Embase up to June 2017
      for relevant clinical trials. Eligible studies include trials in which subjects
      treated with 160 mg of regorafenib daily during the first 21 days of each 28-day
      cycle, and adequate safety data profile reporting thrombocytopenia, anemia,
      neutropenia and leucopenia. Statistical analyses were conducted to calculate the
      overall incidences, relative risks (RRs) and their 95% confidence intervals
      (CIs). A total of 2,341 subjects from 16 trials were included in the present
      studies. The incidences of regorafenib associated all-grade and high-grade
      hematologic toxicities were: thrombocytopenia, 22% and 3%; anemia, 20% and 3%;
      neutropenia, 10% and 2%, and leucopenia, 13% and 2%, respectively. Regorafenib
      treated subjects had a significant increased risk of all-grade (RR=6.35; 95% CI,
      3.19-12.64) and high-grade (RR=6.27; 95% CI, 1.69-23.26) thrombocytopenia, all
      grade (RR=2.76; 95% CI, 1.63-4.68) and high-grade (RR=5.38; 95% CI, 1.60-18.06)
      anemia. Our results suggested that regorafenib therapy was associated with
      significantly increased risks of hematological toxicities, and hematologic
      monitoring at regular intervals should be advised to clinician.

PMID- 29212192
TI  - Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM
      dependent apoptosis induction.
AB  - There is a close relationship between low expression of BIM and resistance to
      epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat
      is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in
      various types of tumor cells, however, this effect is attenuated by the high
      expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung
      cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that
      can inhibit anti-apoptotic proteins expression, might cooperate to activate
      apoptotic signaling and overcome EGFR-TKI resistance. This study aimed to
      investigate the cooperative effect and evaluate possible molecular mechanisms.
      The results showed that vorinostat combined with gefitinib augmented BIM
      expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to
      gefitinib, adding metformin simultaneously could obviously inhibit the expression
      of anti-apoptotic proteins, and further increased expression levels of BIM and
      BAX, and as a result, further improved the sensitivity of gefitinib both on the
      NSCLC cells with intrinsic and acquired resistance to EGFR-TKI. In addition,
      autophagy induced by gefitinib and vorinostat could be significantly suppressed
      by metformin, which might also contribute to enhance apoptosis and improve
      sensitivity of gefitinib. These results suggested that the combination of
      vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI
      resistance associated with BIM-dependent apoptosis in larger heterogeneous
      populations.

PMID- 29212193
TI  - MicroRNA expression profiling in exosomes derived from gastric cancer stem-like
      cells.
AB  - Cancer stem-like cells (CSCs) have been identified as the initial cell in
      formation of cancer. Quiescent CSCs can "hide out" from traditional cancer
      therapy which may produce an initial response but are often unsuccessful in
      curing patients. Thus, levels of CSC in patients may be used as an indicator to
      measure the chance of recurrence of cancer after therapy. The goals of our work
      are to develop specific exosomal miRNA clusters for gastric CSCs that can
      potentially predict which patients are at high risk for developing gastric cancer
      (GC) in order to diagnose GC at an early stage. Here, upon sorting gastric CSCs,
      we initially isolated and characterized exosomes secreted by both gastric CSCs
      and their differentiated cells (DCs). By deep sequencing of each exosomal miRNA
      library, 11 typical differentially expressed miRNAs were identified as signature
      miRNAs for CSC. Gene target prediction, GO annotation and KEGG pathway enrichment
      analysis showed possible functions associated with these signature miRNAs. Hence,
      upon research of exosomal miRNAs that would influence behavior of tumor cells and
      their microenvironment, this study shows that a specific miRNA signature is
      present in CSCs, and implies that a potential miRNA biomarker reflecting the
      stage of gastric cancer progression and metastasis could be developed in the
      foreseeable future.

PMID- 29212194
TI  - Association between miR-31-3p expression and cetuximab efficacy in patients with
      KRAS wild-type metastatic colorectal cancer: a post-hoc analysis of the New EPOC
      trial.
AB  - Background: High miR-31-3p expression is associated with inferior outcomes in
      KRAS wild-type (WT) advanced colorectal cancer patients treated with anti-EGFR
      therapy. This study evaluated miR-31-3p expression in patients with operable
      colorectal liver metastases (LM) enrolled in the New EPOC study. Methods: MiR-31
      3p expression was measured in primary tumors (PT) from 149 KRAS WT patients
      including 71 receiving chemotherapy alone (CT) and 78 receiving chemotherapy plus
      cetuximab (CTX). Each treatment arm was split into tertiles based on miR-31-3p
      expression levels. MiR-31-3p expression was also measured in LM from 94 patients
      with tumor tissue available. Results: The median progression-free survival for
      the combined populations with mid or high miR-31-3p expression was shorter in the
      CTX versus the CT arm (26.7 months versus 12.3 months, HR=2.28 95%CI 1.27; 4.09
      p=0.006). Low miR-31-3p expressers had similar outcomes irrespective of treatment
      (HR=1.06 95%CI 0.43; 2.61 p=0.9). MiR-31-3p expression was correlated between
      paired PT and LM samples in the CT group but not in the CTX group. Conclusions:
      Patients with low miR-31-3p expression in the New EPOC study were not harmed by
      the addition of cetuximab. This supports miR-31-3p as a promising predictive
      biomarker for anti-EGFR therapy in KRAS WT advanced colorectal cancer.

PMID- 29212195
TI  - The adaptive immune system promotes initiation of prostate carcinogenesis in a
      human c-Myc transgenic mouse model.
AB  - Increasing evidence from epidemiological and pathological studies suggests a role
      of the immune system in the initiation and progression of multiple cancers,
      including prostate cancer. Reports on the contribution of the adaptive immune
      system are contradictive, since both suppression and acceleration of disease
      development have been reported. This study addresses the functional role of
      lymphocytes in prostate cancer development using a genetically engineered mouse
      model (GEMM) of human c-Myc driven prostate cancer (Hi-Myc mice) combined with B
      and T cell deficiency (RAG1-/- mice). From a pre-cancerous stage on, Hi-Myc mice
      showed higher accumulation of immune cells in their prostates then wild-type
      mice, of which macrophages were the most abundant. The onset of invasive
      adenocarcinoma was delayed in Hi-MycRAG1-/- compared to Hi-Myc mice and
      associated with decreased infiltration of leukocytes into the prostate. In
      addition, lower levels of the cytokines CXCL2, CCL5 and TGF-beta1 were detected
      in Hi-MycRAG1-/- compared to Hi-Myc mouse prostates. These results from a GEMM of
      prostate cancer provide new insights into the promoting role of the adaptive
      immune system in prostate cancer development. Our findings indicate that the
      endogenous adaptive immune system does not protect against de novo prostate
      carcinogenesis in Hi-Myc transgenic mice, but rather accelerates the formation of
      invasive adenocarcinomas. This may have implications for the development of novel
      treatment strategies.

PMID- 29212196
TI  - Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy
      induction.
AB  - Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare,
      exerting suppressive activity against cancer cell progression in vitro and in
      vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS)
      in different types of cells through regulating various signaling pathways. In our
      study, the effects of juglanin on non-small cell lung cancer were investigated. A
      significant role of juglanin in suppressing lung cancer growth was observed.
      Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and
      poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related
      apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation.
      Anti-apoptotic members Bcl-2 and Bcl-xl were reduced, and pro-apoptotic members
      Bax and Bad were enhanced in cells and animals receiving juglanin. Additionally,
      nuclear factor-kappaB (NF-kappaB), phosphoinositide 3-kinase/protein kinase B
      (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) activation were
      inhibited by juglanin. Further, juglanin improved ROS and induced autophagy. ROS
      inhibitor N-acetyl-l-cysteine (NAC) reversed apoptosis induced by juglanin in
      cancer cells. The formation of autophagic vacoules and LC3/autophagy gene7
      (ATG7)/Beclin1 (ATG6) over-expression were observed in juglanin-treated cells.
      Also, juglanin administration to mouse xenograft models inhibited lung cancer
      progression. Our study demonstrated that juglanin could be a promising candidate
      against human lung cancer progression.

PMID- 29212197
TI  - Paeoniflorin prevents postoperative peritoneal adhesion formation in an
      experimental rat model.
AB  - Although materials and modern surgical techniques have been developed to suppress
      postoperative adhesions, adhesion formation can still occur, and thus, a novel
      effective anti-adhesion drug is greatly needed. In the present study, we explored
      the efficacy of paeoniflorin treatment against postoperative peritoneal adhesions
      and examined the anti-oxidative stress and anti-inflammatory properties of PE.
      Forty-eight male Sprague-Dawley rats were randomly divided into 6 groups for the
      study: the sham, control, hyaluronan and three concentrations (10, 20 and 40
      mg/kg/d) paeoniflorin groups. Abdominal adhesions were created by abrasion of the
      caecum and its opposite abdominal wall. In the paeoniflorin groups, the rats were
      administered daily oral doses of paeoniflorin for 7 days. The abdominal cavities
      of the rats were reopened with a U-shaped incision to macroscopically grade the
      adhesions. Histologic analysis was performed, and oxidative stress, inflammatory
      cytokine, collagen fiber degradation and cytokeratin levels were measured.
      Macroscopic and histopathological measurements revealed that paeoniflorin reduced
      peritoneal adhesion and inflammation. Notably, treatment with paeoniflorin
      reduced the protein levels of TGF-beta1, IL-6 and COX-2. The collagen fiber
      fractions were distinctly lower in the PE groups than in the control group.
      Western blotting analyses showed that paeoniflorin increased MMP-9 and superoxide
      dismutase-2 protein expression and sharply reduced alpha-SMA and COX-2 protein
      expression. Peritoneal mesothelium cells were more continuous and complete in
      animals treated with paeoniflorin. Our study suggests that paeoniflorin can be
      used to ameliorate peritoneal adhesions via anti-oxidative stress and anti
      inflammatory actions during the postoperative period.

PMID- 29212198
TI  - Targeting oral cancer stemness and chemoresistance by isoliquiritigenin-mediated
      GRP78 regulation.
AB  - Cancer stem cells (CSCs) are cells that drive tumorigenesis, contributing to
      metastasis and cancer recurrence as well as resistance to chemotherapy of oral
      squamous cell carcinomas (OSCC). Therefore, approaches to target CSCs become the
      subject of intense research for cancer therapy. In this study, we demonstrated
      that isoliquiritigenin, a chalcone-type flavonoid isolated from licorice root,
      exhibited more toxicity in oral cancer stem cells (OSCC-CSCs) compared to normal
      cells. Treatment of isoliquiritigenin not only inhibited the self-renewal ability
      but also reduced the expression of CSC markers, including the ALDH1 and CD44. In
      addition, the capacities of OSCC-CSCs to invade, metastasize and grow into a
      colony were suppressed by isoliquiritigenin. Most importantly, we showed that
      isoliquiritigenin potentiated chemotherapy along with downregulated expression of
      an ABC transporter that is associated with drug resistance, ABCG2. Moreover, a
      combination of isoliquiritigenin and Cisplatin significantly repressed the
      invasion and colony formation abilities of OSCC-CSCs. Our results suggested that
      administration of isoliquiritigenin reduced the protein expression of mRNA and
      membrane GRP78, a critical mediator of tumor biology. Overexpression of GRP78
      reversed the inhibitory effect of isoliquiritigenin on OSCC-CSCs. Furthermore,
      isoliquiritigenin retarded the tumor growth in nude mice bearing OSCC xenografts.
      Taken together, these findings showed that isoliquiritigenin is an effective
      natural compound that can serve as an adjunct to chemotherapy for OSCC.

PMID- 29212199
TI  - Klf4 reduces stemness phenotype, triggers mesenchymal-epithelial transition (MET)
      like molecular changes, and prevents tumor progression in nasopharygeal
      carcinoma.
AB  - The reprogramming factor Kruppel-like factor 4 (Klf4), one of the Yamanaka's
      reprogramming factors, plays an essential role in reprogramming somatic cells
      into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays
      divergent functions in multiple malignancies, but the biological roles of Klf4 in
      nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that
      Klf4 downregulation in a cohort of human NPC biopsies is significantly associated
      with invasive and metastatic phenotypes of NPC. Our results showed exogenous
      expression of Klf4 significantly inhibited cell proliferation, decreased
      stemness, triggered mesenchymal-epithelial transition (MET)-like molecular
      changes, and suppressed migration and invasion of NPC cells, whereas depletion of
      endogeneous Klf4 by RNAi reversed the aforementioned biological behaviors and
      characheristics. Klf4 silencing significantly enhanced the metastatic ability of
      NPC cells in vivo. In addition, CHIP assay confirmed that E-cadherin is a
      transcriptional target of Klf4 in NPC cells. Additional studies demonstrated that
      Klf4-induced MET-like cellular marker alterations, and reduced motility and
      invasion of NPC cells were mediated by E-cadherin. This study revealed the
      clinical correlation between Klf4 expression and epithelial-mesenchymal
      transition (EMT) biomarkers (including its target gene E-cadherin) in a cohort of
      NPC biopsies. Taken together, our findings suggest, for what we believe is the
      first time, that Klf4 functions as a tumor suppressor in NPC to decrease stemness
      phenotype, inhibit EMT and prevent tumor progression, suggesting that restoring
      Klf4 function may provide therapeutic benefits in NPC.

PMID- 29212200
TI  - Cell-free DNA promoter hypermethylation in plasma as a predictive marker for
      survival of patients with pancreatic adenocarcinoma.
AB  - Introduction: Few prognostic biomarkers are available for pancreatic cancer. The
      aim of this study is to examine the correlation between the survival of
      pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived
      cell-free DNA. Methods: Consecutive patients with pancreatic adenocarcinoma were
      prospectively included and staged according to the TNM classification.
      Methylation-specific PCR of 28 genes was conducted. A survival prediction model
      independent of cancer stage and stage-specific survival prediction models were
      developed by multivariable Cox regression analysis using backward stepwise
      selection. Results: Ninety-five patients with pancreatic adenocarcinoma were
      included. Patients with more than 10 hypermethylated genes had a HR of 2.03 (95%
      CI; 1.15-3.57) compared to patients with fewer hypermethylated genes. Three
      survival prediction models were developed: Total group; (American Society of
      Anesthesiologists score (ASA)=3, GSTP1, SFRP2, BNC1, SFRP1, TFPI2, and WNT5A)
      Risk groups 2, 3 and 4 had a HR of 2.65 (95% CI; 1.24-5.66), 4.34 (95% CI; 1.98
      9.51) and 21.19 (95% CI; 8.61-52.15), respectively, compared to risk group 1.
      Stage I-II; (ASA=3, SFRP2, and MESTv2) Risk groups 2, 3 and 4 had a HR of 4.83
      (95% CI; 2.01-11.57), 9.12 (95% CI; 2.18-38.25) and 70.90 (95% CI; 12.63-397.96),
      respectively, compared to risk group 1. Stage IV; (BMP3, NPTX2, SFRP1, and MGMT)
      Risk group 2 had a HR of 5.23 (95% CI; 2.13-12.82) compared to risk group 1.
      Conclusion: Prediction models based on cell-free DNA hypermethylation stratified
      pancreatic adenocarcinoma patients into risk groups according to survival. The
      models have the potential to work as prognostic biomarkers. However, further
      validation of the results is required to substantiate the findings.

PMID- 29212202
TI  - Enhancing E-cadherin expression via promoter-targeted miR-373 suppresses bladder
      cancer cells growth and metastasis.
AB  - Previous studies showed that miR-373 had the capacity to induce tumor suppressor
      gene E-cadherin expression in prostate cancer cells. However, whether miR-373 can
      activate the expression of E-cadherin in human bladder cancer (BCa) cells and
      inhibit cells remains to be elucidated. Here, we found that both miR-373 and E
      cadherin were low expressed in BCa tissues and cell lines, and significantly
      correlated with tumor stage, grade, and lymph node metastasis. In addition,
      decreased E-cadherin expression or low expression of both miR-373 and E-cadherin
      is associated with poor overall survival in patients with BCa. Transfection of
      miR-373 into BCa cells readily activated E-cadherin expression by targeting
      promoter. Moreover, miR-373 exhibited robust capacity to inhibit cells
      proliferation, suppress migration and invasion by enhancing E-cadherin
      expression, and significantly suppress the growth of xenografts and metastasis in
      nude mice. Altogether, our findings indicate that miR-373 may as a tumor
      suppressor in BCa by activating E-cadherin expression.

PMID- 29212201
TI  - Predicting new indications of compounds with a network pharmacology approach:
      Liuwei Dihuang Wan as a case study.
AB  - With the ever increasing cost and time required for drug development, new
      strategies for drug development are highly demanded, whereas repurposing old
      drugs has attracted much attention in drug discovery. In this paper, we introduce
      a new network pharmacology approach, namely PINA, to predict potential novel
      indications of old drugs based on the molecular networks affected by drugs and
      associated with diseases. Benchmark results on FDA approved drugs have shown the
      superiority of PINA over traditional computational approaches in identifying new
      indications of old drugs. We further extend PINA to predict the novel indications
      of Traditional Chinese Medicines (TCMs) with Liuwei Dihuang Wan (LDW) as a case
      study. The predicted indications, including immune system disorders and tumor,
      are validated by expert knowledge and evidences from literature, demonstrating
      the effectiveness of our proposed computational approach.

PMID- 29212203
TI  - Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular
      carcinoma and its prognostic significance.
AB  - GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the
      synthesis of 60S subunit and maturation, is closely related to cell proliferation
      and growth. Till now, a small number of existing studies have found a
      contradictory dual role of GTPBP4 in cancer. Whether the expression level of
      GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients'
      prognosis or its function and underlying molecular mechanisms still remains
      unclear. In the present study, the above issues were explored for the first time.
      Our results showed that GTPBP4 was overexpressed in HCC and knockdown of GTPBP4
      delayed cell proliferation, impaired colony formation ability, induced cell cycle
      arrest in G2/M period and promoted apoptosis in HCC cell lines. Besides, in vivo
      xenograft nude mice model revealed that GTPBP4 knockdown could significantly
      suppress HCC tumorigenesis. Gene microarray and further pathway enrichment
      analyses indicated that ERBB signaling pathway was the most significantly changed
      one. More importantly, high GTPBP4 expression level significantly correlated to
      the poor prognosis of HCC patients. Taken together, all these findings suggest
      that GTPBP4 serves as an oncogene and plays a pivotal role in HCC development,
      which will be a potential therapeutic target or a biomarker for HCC.

PMID- 29212204
TI  - MYC overexpression with its prognostic and clinicopathological significance in
      breast cancer.
AB  - Background: Proto-oncogene MYC has been indicated to promote progression of many
      cancers. However, prognostic and clinicopathological significance of MYC in
      breast cancer need further evaluation. Methods: We searched EMBASE and PubMed
      databases to find useful studies. We analyzed relationships between high MYC
      expression and prognostic data/ clinicopathological features through hazard ratio
      (HR) and odds ratio (OR). Each statistical test was two-sided. Results: There
      were 29 studies (36 cohorts) with 12621 patients enrolled in our study The MYC
      overexpression was associated with worse DFS/RFS (disease/relapse free survival)
      in 11 studies (16 cohorts) with 5390 patients, and OS (overall survival) of 7
      studies (8 cohorts) with 2672 patients. Subgroup analysis according to
      ethnicity/technique/data source displayed that MYC overexpression was associated
      with poor DFS/RFS in FISH, other technique, all data source and Asian/Non-Asian
      subgroup, and worse OS in all subgroups. In addition, MYC overexpression was
      related to large tumor size, high histologic grade, lymph node metastasis,
      negative hormone receptors and positive Ki67 expression. Conclusions: Our results
      showed that MYC overexpression was associated with worse prognosis and high risk
      of breast cancer, especially in patients with negative hormone receptors, which
      highlighted the potential of MYC as a significant prognostic biomarker of breast
      cancer.

PMID- 29212205
TI  - JNK inhibitor alleviates apoptosis of fetal neural stem cells induced by
      emulsified isoflurane.
AB  - : Isoflurane can provide both neuroprotection and neurotoxicity in various
      culture models and in rodent developing brains. Emulsified Isoflurane (EI) is an
      emulsion formulation of isoflurane, while its underlying molecular mechanism of
      developemental nerve toxicity largely remains unclear. We hypothesized that EI
      induced fetal neural stem cells (FNSCs) apoptosis, endoplasmic reticulum (ER)
      stress and c-Jun N-terminal kinase (JNK) activation. FNSCs were isolated from the
      cortex of SD rats during 14 days of gestation. The cell viability, cell apoptotic
      rates and the expression of apoptosis-related protein Caspase3, inositol
      requiring enzyme 1 (IRE1), poly (adenosine diphosphate-ribose) polymerase (PARP),
      Bax, Bcl-2, JNK, p-JNK and XBP1 were determined. Specific inhibition was
      performed by siRNA-targeting of JNK in FNSCs. EI could increase the p-JNK, JNK
      and caspase3 protein expression, the JNK pathway was activated by EI, and EI
      induced apoptosis was blocked by inhibiting JNK pathway with SP600125 or JNK
      small interfering RNA (siRNA), EI enhanced the level of IRE1, PARP, Bax/Bcl-2 and
      XBP1, which led FNSCs to apoptosis and ER stress. Meanwhile, dilatation of the ER
      lumens in FNSCs treated by EI for 24 h was significant. Green fluorescent protein
      (GFP) positive cell ratios were significantly decreased by FNSCs transfecting
      with JNK gene silencing. JNK was efficiently silenced in siRNA-JNK1 group. The
      results provided in-vitro evidence which supports that the underlying mechanisms
      of EI-induced apoptosis are the induction of ER stress and sequent JNK
      activation. Together, these data suggest that JNK inhibiting might be applied for
      improving therapeutic outcomes in anesthestics-induced neurotoxicity. HIGHLIGHTS:
      1. Prolonged treatment with high-dose EI decreased the survival level of FNSCs by
      inducing apoptosis and inhibiting proliferation via the JNK signaling pathway. 2.
      EI induced ER stress and sequent JNK activation. 3. JNK inhibiting might be
      applied for improving therapeutic outcomes in anesthestics-induced neurotoxicity.

PMID- 29212206
TI  - LINE-1 methylation in peripheral blood leukocytes and clinical characteristics
      and prognosis of prostate cancer patients.
AB  - Global DNA methylation of long interspersed nucleotide elements (LINE-1) in
      leukocytes has been suggested to be a risk factor for a few cancers. There has
      been no report of LINE-1 methylation in leukocytes as a risk factor for
      aggressive prostate cancer at diagnosis and prognosis after treatments. In this
      study, we measured the leukocyte DNA methylation of LINE-1 in 795 PCa patients
      and compared the methylation levels across different clinical subgroups. We then
      determined the association of LINE-1 methylation in leukocytes with
      clinicopathological variables at diagnosis using logistic regression analysis and
      biochemical recurrence in patients receiving active treatments (prostatectomy and
      radiotherapy) using Cox proportional hazard model after adjusting for age, BMI,
      smoking status, pack year, D'Amico risk groups, and treatments. Overall, the DNA
      methylation of LINE-1 was not associated with the risk of being diagnosed with
      high-risk prostate cancer or the risk of biochemical recurrence upon active
      treatments. Future studies are warranted to investigate other types of repetitive
      element methylation and longitudinal changes of global methylation in relation to
      prostate cancer risk and prognosis.

PMID- 29212207
TI  - DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial
      mesenchymal transition.
AB  - Chemoresistance limits treatment efficacy in gastric cancer and doxorubicin
      resistance is common in gastric cancer cells. Dual specificity phosphatase 4
      (DUSP4) has been associated with tumor progression. This study aimed to
      investigate the mechanism of DUSP4 regulating doxorubicin resistance in gastric
      cancer cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU)
      incorporation assay were used to measure cell viability and proliferation in
      gastric cancer cells treated with doxorubicin. The expression of DUSP4, E
      cadherin and Vimentin protein was detected by Western blotting. Overexpression of
      DUSP4 was more resistant to doxorubicin in gastric cancer cells. Knockdown of
      DUSP4 increased the sensitivity of gastric cancer cells to doxorubicin. Moreover,
      up-regulation of DUSP4 promoted the Epithelial-Mesenchymal Transition (EMT) in
      gastric cancer cells, but blocking the EMT using a Twist siRNA increased the
      sensitivity of gastric cancer cells to doxorubicin and confirmed the EMT was
      involved in DUSP4-mediated doxorubicin resistance. These findings demonstrated
      that DUSP4 could enhance doxorubicin resistance by promoting EMT in gastric
      cancer cells.

PMID- 29212208
TI  - Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth
      and improves survival in immune competent mice.
AB  - Background: Chemotherapy initially reduces the tumor burden in patients with
      ovarian cancer. However, tumors recur in over 70% of patients, creating the need
      for novel therapeutic approaches. Methods: We evaluated Ruxolitinib, an FDA
      approved JAK 1/2 kinase inhibitor, as a potential adjunctive therapy for use with
      low-dose Taxol (Paclitaxel) by assessing the impact on in vitro proliferation and
      colony formation of ID8 cells or human TOV-112D ovarian cancer cells, as well as
      flow cytometric measurement of surface markers associated with cellular stress
      and stemness by ID8 cells. The syngeneic ID8 murine model of ovarian cancer was
      used to assess the impact of Ruxolitinib and Taxol, individually and in
      combination, on tumor initiation and growth, as well as capacity to extend
      survival. Results: Ruxolitinib (<=10 MUM) sensitized both ID8 and TOV-112D cells
      to low concentrations of Taxol (<=5 nM), limiting cell proliferation and colony
      formation in vitro. Mechanistically, we demonstrated that Taxol induced
      expression of stress and stemness markers including GRP78 and CD133 was
      significantly reduced by addition of Ruxolitinib. Finally, we demonstrated that a
      single administration of a low-dose of Taxol (10 mg/Kg) together with daily
      Ruxolitinib (30 mg/Kg; which is equivalent to plasma concentrations of ~ 0.01 MUM
      steady-state) limited ID8 tumor growth in vivo and significantly extended median
      survival up to 53.5% (median 70 v 107.5 days) as compared to control mice.
      Conclusion: Together, these data support the use of Ruxolitinib in combination
      with low-dose Taxol as a therapeutic approach with the potential for improved
      efficacy and reduced side effects for patients with recurrent ovarian cancer.

PMID- 29212209
TI  - Targeted inhibition of glutaminase as a potential new approach for the treatment
      of NF1 associated soft tissue malignancies.
AB  - Many cancer cells rely on glutamine as the source of carbon molecules to feed the
      biosynthetic pathways and are often addicted to glutaminolysis. Inhibitors of
      glutaminase activity have gained attention in the last few years due to their
      anti-proliferative effect and ability to induce apoptosis in some cancers.
      Although it is a promising therapeutic approach, its efficacy or the role played
      by glutamine in modulating cell proliferation in NF1 associated tumors has never
      been studied. We report for the first time, a strong correlation between the NF1
      status of tumor cells and increased sensitivity to glutamine deprivation and
      glutaminase inhibition. Soft-tissue cell lines null for NF1 were highly dependent
      on glutamine for proliferation and showed decreased mTORC1 and Ras activity in
      response to glutaminase inhibition. Re-addition of glutamine or intermediary
      metabolite such as glutamate to the media restored mTORC1 and Ras activity. SiRNA
      mediated NF1 knockdown in wild-type NF1 cell line shows increased sensitivity to
      glutaminase inhibition. Conversely, NF1 overexpression in NF1 null cell lines
      results in reduced sensitivity to glutaminase inhibition, and restores mTORC1
      signaling and Ras activity. These findings provide new insights into the role
      played by glutamine metabolism in NF1 associated tumors and strongly warrant
      further investigation as a potential therapy in the NF1 disease setting.

PMID- 29212210
TI  - miR-21 silencing ameliorates experimental autoimmune encephalomyelitis by
      promoting the differentiation of IL-10-producing B cells.
AB  - IL-10-producing regulatory B (IL-10+ Breg) cells promote tolerance in autoimmune
      diseases and transplantation. However, it remains unclear whether microRNAs are
      involved in the development of IL-10+ Breg cells. Here, we found that microRNA-21
      (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated
      region of IL-10 mRNA. We also demonstrated that IL-10+ Breg cells exhibit lower
      miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative
      regulator of the differentiation of IL-10+ Breg cells. Accordingly, specific
      inhibition of miR-21 using antisense oligonucleotides markedly promoted B cell IL
      10 expression. Thus, IL-10 is a direct target of miR-21. Moreover, silencing of
      miR-21 significantly alleviated the severity of experimental autoimmune
      encephalomyelitis (EAE), and this change was associated with an increase in the
      number of IL-10+ Breg cells. Finally, we demonstrated that miR-21-silenced B
      cells exert their suppressive activity through effector T cells in an IL-10
      dependent manner. Thus, we characterized a B cell-intrinsic microRNA pathway that
      inhibits the differentiation of IL-10+ Breg cells and promotes autoimmunity. miR
      21 silencing therefore represents a new therapeutic strategy for the treatment of
      autoimmune diseases.

PMID- 29212211
TI  - SETD7 is a prognosis predicting factor of breast cancer and regulates redox
      homeostasis.
AB  - SETD7 is a methyltransferase that specifically catalyzes the monomethylation of
      lysine 4 on histone H3. A variety of studies has revealed the role of SETD7 in
      posttranslational modifications of non-histone proteins. However, the prognostic
      value of SETD7 on breast cancer and the ability of SETD7 of regulating intrinsic
      redox homeostasis has never been investigated. In this study, using The Cancer
      Genome Atlas (TCGA) database, we revealed that SETD7 was a potential prognostic
      marker of breast cancer. Median survival time of patients with low SETD7
      expression (18.1 years) was twice than that of SETD7 low-expressed patients (9.5
      years). We demonstrated that SETD7 promoted tumor cell proliferation and
      prevented cell apoptosis and that SETD7 delicately maintained the redox
      homeostasis through regulating the levels of GSH/GSSG and ROS. Further studies
      indicated that SETD7 was a positive activator of KEAP1-NRF2 pathway. Using dual
      luciferase assay, we revealed the role of SETD7 as a transcriptional activator of
      antioxidant enzymes. Downregulation of SETD7 in MCF7 and MDA-MB-231 cells
      impaired the expression of antioxidant enzymes and induces imbalance of redox
      status. Together, we proposed SETD7 as a prognostic marker of breast cancer and a
      novel antioxidant promoter under oxidative stress in breast cancer.

PMID- 29212212
TI  - ADAMTS1-mediated targeting of TSP-1 by PPARdelta suppresses migration and
      invasion of breast cancer cells.
AB  - Migration and invasion of cancer cells into surrounding tissue is a key stage of
      cancer metastasis. Here, we show that peroxisome proliferator-activated receptor
      (PPAR) delta regulates migration and invasion of human breast cancer cells via
      thrombospondin-1 (TSP-1) and its degrading protease, a disintegrin and
      metalloprotease domains with thrombospondin motifs 1 (ADAMTS1). Activation of
      PPARdelta by GW501516, a specific ligand for PPARdelta, led to marked inhibition
      in the cell migration and TSP-1 expression of breast cancer. These effects were
      suppressed by small interfering RNA-mediated knock-down of ADAMTS1, indicating
      that ADAMTS1 is involved in PPARdelta-mediated inhibition of migration and TSP-1
      expression in breast cancer cells. In addition, ligand-activated PPARdelta
      upregulated expression of ADAMTS1 at the transcriptional level via binding of
      PPARdelta to a direct repeat-1 site within the ADAMTS1 gene promoter.
      Furthermore, ligand-activated PPARdelta suppressed invasion of breast cancer
      cells in an ADAMTS1-dependent manner. Taken together, these results demonstrate
      that PPARdelta suppresses migration and invasion of breast cancer cells by
      downregulating TSP-1 in a process mediated by upregulation of ADAMTS1.

PMID- 29212213
TI  - The bromodomain and extraterminal domain inhibitor bromosporine synergistically
      reactivates latent HIV-1 in latently infected cells.
AB  - The long-lived latent HIV-1 reservoir is the major barrier for complete cure of
      Acquired Immune Deficiency Syndrome (AIDS). Here we report that a novel
      bromodomain and extraterminal domain (BET) inhibitor bromosporine which can
      broadly target BETs, is able to potently reactivate HIV-1 replication in
      different latency models alone and more powerful when combined with prostratin or
      TNF-alpha. Furthermore, the treatment with bromosporine induced HIV-1 full-length
      transcripts in resting CD4+ T cells from infected individuals with suppressive
      antiretroviral therapy (ART) ex vivo, with no obvious cytotoxicity or global
      activation of T cell. Finally, our data suggest that Tat plays a critical role in
      the bromosporine-mediated reactivation of latent HIV-1, which involved the
      increase of CDK9 T-loop phosphorylation. In summary, we found that the BET
      inhibitor bromosporine, alone or with other activators, might be a candidate for
      future HIV-1 eradication strategies.

PMID- 29212214
TI  - Association of the neoadjuvant chemotherapy cycle with survival outcomes in
      patients with locoregionally advanced nasopharyngeal carcinoma: a propensity
      matched analysis.
AB  - Neoadjuvant chemotherapy (NAC) is widely used to treat locoregionally advanced
      nasopharyngeal carcinoma (NPC). To determine the optimal number of NAC cycles, we
      assessed the effect of NAC cycle on survival outcomes of locoregionally advanced
      NPC patients receiving NAC before concurrent chemotherapy and intensity-modulated
      radiotherapy. Clinical data from 1,188 non-metastatic NPC patients were
      retrospectively reviewed. All received >=2 cycles of NAC added to concurrent
      chemoradiotherapy. Propensity score matching (PSM) was used to identify paired
      patients according to various covariates. In total, 297 pairs were selected.
      After a median follow-up time of 57 months (range: 7 to 104 months), the 5-year
      locoregional relapse-free survival, distant metastasis-free survival (DMFS),
      progression-free survival (PFS), and overall survival rates in patients treated
      with 2 cycles vs. 3 to 4 cycles of NAC were 91.3% vs. 87.2% (P=0.149), 93.3% vs.
      88.5% (P=0.043), 88.7% vs. 81.7% (P=0.037), and 94.0% vs. 92.6% (P=0.266),
      respectively. On multivariate analysis, 2 cycles of NAC were associated with
      improved DMFS (hazard ratio, 0.499; P=0.038) and PFS (hazard ratio, 0.585;
      P=0.049). NAC cycle was an independent prognosticator of DMFS and PFS in
      univariate and multivariate analyses. Thus, 2 cycles of NAC appear sufficient, as
      additional cycles were not associated with added survival benefit for
      locoregionally advanced NPC.

PMID- 29212215
TI  - Betanodavirus B2 protein triggers apoptosis and necroptosis in lung cancer cells
      that suppresses autophagy.
AB  - The betanodavirus B2 protein targets the mitochondria and acts as a "death
      factor", but its effect on lung cancer cells is unknown. We examined the effect
      of the B2 protein on triggering apoptosis or necroptosis via P53-dependent and
      P53-independent pathways and increased in suppression of autophagy. The B2
      protein targets the mitochondria of A549 (P53+/+) and H1299 (P53-/-) lung cancer
      cells due to a specific signal sequence (41RTFVISAHAA50). This triggers
      generation of reactive oxygen species within the mitochondria, and a minor stress
      response in A549 cells, but a strong stress response in H1299 cells. We examined
      the molecular mechanism of this cell death pathway, and found that B2 protein
      induces the P53/Bax-mediated apoptotic pathway in A549 cells, and that a P53
      specific inhibitor (pifithrin-alpha) switches this response to RIP3-mediated
      necroptosis. On the other hand, B2 induces RIP3-mediated necroptosis pathway in
      H1299 cells, and a necroptosis inhibitor (necrostatin-1) switches this response
      to the apoptotic pathway. Both types of cell death signals inhibited autophagy
      via a tightly increased balance of beclin-1 and Bcl-2. Thus, B2 protein triggers
      P53-dependent apoptosis in A549 cells and ROS/RIP3-mediated necroptosis in H1299
      cells, and crosstalk of these pathways limits initiation of autophagy. These
      findings provide new insights into the possible control and treatment of lung
      cancer.

PMID- 29212216
TI  - Naringin improves random skin flap survival in rats.
AB  - Background: Random-pattern flap transfer is commonly used to treat soft-tissue
      defects. However, flap necrosis remains a serious problem. Naringin accelerates
      angiogenesis by activating the expression of vascular endothelial growth factor
      (VEGF). In the present study, we investigated whether naringin improves the
      survival of random skin flaps. Results: Compared with controls, the naringin
      treated groups exhibited significantly larger mean areas of flap survival,
      significantly increased SOD activity and VEGF expression, and significantly
      reduced MDA level. Hematoxylin and eosin (HE) staining revealed that naringin
      promoted angiogenesis and inhibited inflammation. Materials and Methods:
      "McFarlane flap" models were established in 90 male Sprague-Dawley (SD) rats
      divided into three groups: a 40 mg/kg control group (0.5 % sodium
      carboxymethylcellulose), a 40 mg/kg naringin-treated group, and an 80 mg/kg
      naringin-treated group. The extent of necrosis was measured 7 days later, and
      tissue samples were subjected to histological analysis. Angiogenesis was
      evaluated via lead oxide-gelatin angiography, immunohistochemistry, and laser
      Doppler imaging. Inflammation was evaluated by measurement of serum TNF-alpha
      (tumor necrosis factor-alpha) and IL-6 (interleukin-6) levels. Oxidative stress
      was assessed by measuring superoxide dismutase (SOD) activity and the
      malondialdehyde (MDA) level. Conclusion: Naringin improved random skin flap
      survival.

PMID- 29212217
TI  - TMED2 promotes epithelial ovarian cancer growth.
AB  - TMED2 is involved in morphogenesis of the mouse embryo and placenta. We found
      that expression of TMED2 was higher in epithelial ovarian cancer tissues than
      normal ovarian tissues. Silencing TMED2 decreased cell proliferation, migration,
      and invasion. Ectopic expression of TMED2 increased cell proliferation, migration
      and invasion. Silencing TMED2 inhibited ovarian cancer growth in mice. Silencing
      TMED2 inhibited IGF2/IGF1R/PI3K/Akt pathway. In agreement, ectopically expressed
      TMED2 activated IGF2/IGF1R/PI3K/Akt pathway. Mechanistic study revealed that
      TMED2 directly binds to AKT2, thereby facilitating its phosphorylation. We also
      found that TMED2 increased IGF1R expression by competing for miR-30a. Thus, TMED2
      is oncogenic and a potential target for epithelial ovarian cancer therapy.

PMID- 29212218
TI  - Optimized guide RNA structure for genome editing via Cas9.
AB  - The genome editing tool Cas9-gRNA (guide RNA) has been successfully applied in
      different cell types and organisms with high efficiency. However, more efforts
      need to be made to enhance both efficiency and specificity. In the current study,
      we optimized the guide RNA structure of Streptococcus pyogenes CRISPR (Clustered
      Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR-associated) system
      to improve its genome editing efficiency. Comparing with the original functional
      structure of guide RNA, which is composed of crRNA and tracrRNA, the widely used
      chimeric gRNA has shorter crRNA and tracrRNA sequence. The deleted RNA sequence
      could form extra loop structure, which might enhance the stability of the guide
      RNA structure and subsequently the genome editing efficiency. Thus the genome
      editing efficiency of different forms of guide RNA was tested. And we found that
      the chimeric structure of gRNA with original full length of crRNA and tracrRNA
      showed higher genome editing efficiency than the conventional chimeric structure
      or other types of gRNA we tested. Therefore our data here uncovered the new type
      of gRNA structure with higher genome editing efficiency.

PMID- 29212219
TI  - MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through
      suppressing Hspb8 expression.
AB  - Previously, we found several genes are involved in myocardial ischemia
      reperfusion (M-I/R) injury. In this report, we first developed a mouse model of M
      I/R injury and demonstrated microRNA-126a-5p was associated with the M-I/R injury
      by using high-throughput microRNA expression analysis. We further investigated
      the expression and function of microRNA-126a-5p during mouse M-I/R injury. We
      observed high expression of microRNA-126a-5p in the M-I/R mice and increased
      levels of LDH and CK-MB (damage markers) in the serum. H2O2 and
      hypoxia/reoxygenation (H/R) treatment significantly increased the expression of
      microRNA-126a-5p in H9C2 cells in concentration- and time-dependent manners.
      Moreover, microRNA-126a-5p overexpression in H9C2 cells inhibited cell viability
      but increased LDH release and caspase 3 activity. Cardiac function analysis based
      on the measurements of hemodynamic parameters showed that microRNA-126a-5p
      expression ablation in M-I/R injured mice led to the reversal of the symptoms
      caused by M-I/R injury. Transesophageal echocardiography also revealed that the
      values of LVIDd and LVIDs were decreased while the values of LVFS% and LVEF% were
      increased in M-I/R injured mice after treatment with microRNA-126a-5p inhibitor,
      compared with the M-I/R injured mice treated with the control. Bioinformatic
      analysis demonstrated that Hspb8, a protective protein in myocardium, was the
      target of microRNA-126a-5p. Thus, these findings indicated that microRNA-126a-5p
      was up-regulated in mouse M-I/R model and promoted M-I/R injury in vivo through
      suppressing the expression of Hspb8, which may shed light on the development of
      potential therapeutic target for M-I/R injury.

PMID- 29212220
TI  - A new staging system for nasopharyngeal carcinoma based on intensity-modulated
      radiation therapy (IMRT).
AB  - Objective: This study is to establish a new staging system for nasopharyngeal
      carcinoma (NPC) based on the magnetic resonance imaging (MRI) and intensity
      modulated radiation therapy (IMRT). Methods: Totally 492 patients with
      nasopharyngeal carcinoma were included in this study. These patients were
      diagnosed by pathological detection (without distant metastasis) and underwent
      the initial treatment of IMRT. These patients were subjected to the staging with
      the International Union against Cancer/American Joint Committee on Cancer
      (UICC/AJCC) staging system. Survival rates were calculated by the Kaplan-Meier
      method. Log-rank test was used to calculate the single factor prognosis, and the
      COX risk model was used to analyze the multivariate prognosis. Results: In these
      492 patients, according to our recommended new T and N staging criteria, there
      were 290 cases of T1 and 202 cases of T2; there were 64 cases of N0, 159 cases of
      N1, 226 cases of N2, and 43 cases of N3. Univariate and multivariate analyses
      showed that the T and N staging combination parameters were independent
      prognostic factors, which affected the overall survival rates and tumor-free
      survival rates. According to risk difference and survival curve distribution, the
      following new clinical staging criteria were established: stage I (T1N0M0), stage
      II (T1N1M0 and T2N0M0), stage III (T1N2M0 and T2N1-2M0), stage IVa (T1-2N3M0),
      and stage IVb (TxNxM1). Conclusion: A new staging system for NPC based on MRI and
      IMRT has been recommended, which provides valuable evidence for disease treatment
      and prognosis prediction.

PMID- 29212221
TI  - Inhibited effects of CAPE-pNO2 on cervical carcinoma in vivo and in vitro and its
      detected metabolites.
AB  - The development of advanced cervical cancer therapies is a particularly urgent
      need due to the strong side effects and toxicities of current treatments. Caffeic
      acid phenethyl ester (CAPE) exhibits broad-spectrum antitumor activities and
      little toxicity or side effects. In our previous study, caffeic acid para-nitro
      phenethyl ester (CAPE-pNO2) significantly improved the effect of anti-platelet
      aggregation and attenuated myocardial ischemia. Based on this finding, we aimed
      to further explore the antitumor activity of CAPE-pNO2 in cervical cancer cells
      and tumor xenografts. In addition, we assessed the biotransformation of CAPE-pNO2
      in cervical cancer cells. Our study demonstrated that both CAPE and CAPE-pNO2 can
      inhibit cell proliferation via the induction of G2/M cell cycle arrest. More
      importantly, CAPE-pNO2 dramatically induced cell apoptosis via significant down
      regulation of pro-caspase-3, pro-caspase-9, Bcl-2, Cyclin B1 and Cdc2 and up
      regulation of cleaved-caspase-3, Bax, CytoC and P21Cip1. Moreover, CAPE and CAPE
      pNO2 significantly suppressed the growth and angiogenesis of nude mice
      xenografts. CAPE and CAPE-pNO2 were found to degrade into four and six
      metabolites, respectively. The metabolites of CAPE and CAPE-pNO2 were different,
      and the major metabolic pathway may be phase II reactions. These results suggest
      that CAPE-pNO2 induced cell apoptosis and cell cycle arrest via a strong
      regulatory effect on relevant apoptotic proteins. Therefore, CAPE-pNO2 should be
      further studied as a potent anti-cancer agent.

PMID- 29212222
TI  - Antitumor activity of a newly developed monoclonal antibody against ROR1 in
      ovarian cancer cells.
AB  - Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) is a tyrosine-protein
      kinase transmembrane receptor and ROR1 overexpression is associated with a poor
      prognosis in various cancers, including ovarian cancer. Targeting of ROR1 has
      been evaluated as a novel cancer therapy strategy. This study developed a novel
      chimeric anti-ROR1 Fab antibody (named ROR1-cFab) and then assessed the antitumor
      activity of this antibody in ovarian cancer cells, an in vitro model of
      preclinical cancer therapy. A ROR1-cFab prokaryotic expression vector was
      constructed from positive fusion cells (splenocytes from mice with high ROR1
      immune titers were fused with myeloma cells) after three rounds of sub-clone
      affinity screening. Then, a variety of assays were employed to assess the binding
      selectivity and specificity of ROR1-cFab to ROR1 protein. Furthermore, CCK8, flow
      cytometric apoptosis, wound healing, and Transwell migration assays were used to
      assess antitumor activity of this newly developed anti-ROR1 antibody in ovarian
      cancer cells. We demonstrated that ROR1-cFab could specifically bind to ROR1
      protein and ROR1-positive ovarian cancer A2780 cells. Functional assays revealed
      that ROR1-cFab inhibited tumor cell proliferation and migration, as well as
      inducing apoptosis of ROR1-positive A2780 cells in a dose dependent manner. These
      effects were not observed in ROR1-negative lose386 cells. In conclusion, ROR1
      cFab is a novel anti-ROR1 antibody with a high affinity to ROR1 protein and
      inhibitory effects on ROR1-positive cells. Future studies will determine whether
      the ROR1-cFab might be a promising candidate for treatment of ROR1-positive
      ovarian cancer.

PMID- 29212223
TI  - Human renal adipose tissue induces the invasion and progression of renal cell
      carcinoma.
AB  - We evaluated the effects of conditioned media (CMs) of human adipose tissue from
      renal cell carcinoma located near the tumor (hRATnT) or farther away from the
      tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and
      ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose
      tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from
      hRATnT and hRATfT incubation. Proliferation, adhesion and migration were
      quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or
      control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from
      hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on
      cell lines incubated with CMs. No differences in proliferation of cell lines was
      found after 24 h of treatment with CMs. All cell lines showed a significant
      decrease in cell adhesion and increase in cell migration after incubation with
      hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of
      versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells
      decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control
      CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN
      incubated with hRATnT-CMs. This result could partially explain the observed
      changes in migration and cell adhesion. We conclude that hRATnT released factors,
      such as leptin and versican, could enhance the invasive potential of renal
      epithelial cell lines and could modulate the progression of the disease.

PMID- 29212224
TI  - HADC5 deacetylates MKL1 to dampen TNF-alpha induced pro-inflammatory gene
      transcription in macrophages.
AB  - Macrophage-dependent inflammatory response on the one hand functions as a key
      line of defense in host immunity but on the other hand underlies the pathogenesis
      of a host of human pathologies when aberrantly activated. Our previous
      investigations have led to the identification of megakaryocytic leukemia 1 (MKL1)
      as a key co-factor of NF-kappaB/p65 participating in TNF-alpha induced pro
      inflammatory transcription in macrophages. How post-translational modifications
      contribute to the modulation of MKL1 activity remains an underexplored subject
      matter. Here we report that the lysine deacetylase HDAC5 interacts with and
      deacetylates MKL1 in cells. TNF-alpha treatment down-regulates HDAC5 expression
      and expels HDAC5 from the promoters of pro-inflammatory genes in macrophages. In
      contrast, over-expression of HDAC5 attenuates TNF-alpha induced pro-inflammatory
      transcription. Mechanistically, HDAC5-mediated MKL1 deacetylation disrupts the
      interaction between MKL1 and p65. In addition, deacetylation of MKL1 by HDAC5
      blocks its nuclear translocation in response to TNF-alpha treatment. In
      conclusion, our work has identified an important pathway that contributes to the
      regulation of pro-inflammatory response in macrophages.

PMID- 29212225
TI  - The relevance of prelamin A and RAD51 as molecular biomarkers in cervical cancer.
AB  - Along with their role in the maintenance of nuclear architecture, nuclear lamins
      also control genomic stability, DNA damage repair, transcription, cell
      proliferation, differentiation and senescence. Recent reports reveal that
      prelamin A-processing defects play a role in cancer development by impacting on
      transcription of key players in the maintenance of the genome stability,
      including RAD51. Here, we performed a 'proof of concept' study evaluating the
      role of prelamin A and RAD51 expression in clinical outcome of cervical cancer
      patients. We analyzed biomarker expression by immunohistochemistry in tumor
      material from locally advanced cervical cancer (LACC) patients (n=66) and
      correlated data with clinicopathological parameters and with response to
      neoadjuvant chemoradiation (CT/RT). In LACC patients who underwent neoadjuvant
      CT/RT the percentage of cases showing high prelamin A levels was greater in
      patients who completely responded to treatment (25 of 40, 62.5%) than in patients
      with macroscopic residual tumor (6 of 26, 23.1%, p=0.0024). Conversely, patients
      showing high RAD51 expression were less likely to respond to treatment (14 of 26,
      53.8%) than were those with low protein levels (12 of 40, 30%, p=0.072). Only
      prelamin A retained an independent role in predicting response to treatment
      (p=0.003), while RAD51 approached statistical significance (p=0.07). Notably,
      high RAD51 expression highly significantly predicted poor outcome, emerging as an
      independent prognostic factor for disease free survival (p=0.038), while
      approaching statistical significance for overall survival (p=0.09). Our findings
      provide a framework for future prospective studies investigating molecular
      predictors of response to neoadjuvant chemoradiotherapy in LACC patients.

PMID- 29212226
TI  - Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through
      regulation of androgen receptor signaling in prostate cancer.
AB  - Docetaxel is the standard chemotherapy for metastatic castration-resistant
      prostate cancer (CRPC). However, nearly all patients ultimately become refractory
      due to the development of docetaxel resistance. The transcribed ultraconserved
      regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely
      conserved across species and are involved in carcinogenesis including prostate
      cancer (PC). In this study, we investigated the transcriptional levels of 26
      representative T-UCRs and determined the regions that were differentially
      expressed in PC. Quantitative real-time polymerase chain reaction analysis
      revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT
      assay and wound healing assay revealed that Uc.63+ was involved in cell growth
      and cell migration. miR-130b was predicted to have binding sites within the
      Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the
      overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the
      expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+
      increased the expression of AR and its downstream molecule PSA and promoted
      resistance to docetaxel through AR regulation. In patients treated with
      docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was
      higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover,
      Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated
      with a worse prognosis (P = 0.020). These results substantially support the
      important role that Uc.63+ plays in PC progression by interacting with miR-130b
      and indicate that Uc.63+ could potentially be a promising serum marker for
      deciding the best treatment for patients with CRPC.

PMID- 29212227
TI  - Shift in energy metabolism caused by glucocorticoids enhances the effect of
      cytotoxic anti-cancer drugs against acute lymphoblastic leukemia cells.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy.
      Treatments include glucocorticoids (GCs) such as dexamethasone (Dex) and
      prednisolone, which may be of value when used alongside cytotoxic anti-cancer
      drugs. To predict therapeutic efficacy of GCs, their activity against ALL cells
      is usually examined prior to chemotherapy; however, few studies have examined
      their effects when used in combination with other drugs. The paradox is that
      cytotoxic anti-cancer drugs that are effective against proliferating cancer cells
      show synergistic effects when used with GCs that prevent cell proliferation. To
      address this point, we investigated intracellular energy metabolism in ALL CCRF
      CEM cell clones classified according to their sensitivity to Dex and cytotoxic
      anti-cancer drugs in bulk cultures of mixed cells. We found that Dex suppressed
      glycolysis, the most important metabolic system in cancer cells, in cells that
      were damaged by etoposide (a cytotoxic anti-cancer drug), and the cells showed a
      concomitant increase in mitochondrial oxidative phosphorylation. Furthermore,
      autophagy, an intracellular bulk degradation system, regulated mitochondrial
      viability. We also found that mitochondria, whose function is enhanced by Dex,
      were susceptible to anti-cancer drugs that inhibit respiratory complexes (e.g.,
      etoposide and daunorubicin), resulting in increased production of reactive oxygen
      species and subsequent cytotoxicity. Taken together, the present study points the
      way toward a more accurate prediction of the sensitivity of ALL cells to the
      combined action of anti-cancer drugs and GCs, by taking into consideration the
      shift in intracellular energy metabolism caused by GCs: namely, from glycolysis
      to mitochondrial oxidative phosphorylation mediated by autophagy.

PMID- 29212228
TI  - Inhibition of tumor cell growth by adenine is mediated by apoptosis induction and
      cell cycle S phase arrest.
AB  - Gekko swinhonis has a long standing history in Chinese traditional medicine
      recognized for its application in treating patients with terminal cancer.In order
      to discover novel anticancer drugs with high anti-tumor efficacy and low toxicity
      to normal cells, we aim to investigate the anti-tumor components from Gekko
      swinhonis. Four nucleosides from the extracted samples were enriched, namely
      adenosine, guanosine, thymidine and inosine. We evaluated the antitumor effect of
      the four nucleosides and found that adenosine possessed the strongest anti-tumor
      effect. Besides, adenine could inhibit the growth of Bel-7402 and Hela cells in a
      dose and time dependent manner, but not normal human cervical keratinocytes. Bel
      7402 and Hela cells had undergone apoptosis 48 hours after treatment as evidenced
      by morphologic changes under TEM, while adenine blocked cell cycle of tumor cells
      at S phase and subsequently causing cell cycle exit and promoting apoptosis.
      Moreover, the pharmacokinetics of adenine was stable in cell culture medium for
      up to 72 hours. Combining its potency with stability, we conclude adenine makes a
      promising candidate for an anti-tumor drug.

PMID- 29212229
TI  - Solid formulation of a supersaturable self-microemulsifying drug delivery system
      for valsartan with improved dissolution and bioavailability.
AB  - In order to improve the dissolution and oral bioavailability of valsartan (VST),
      and reduce the required volume for treatment, we previously formulated a
      supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of
      VST (80 mg), Capmul(r) MCM (13.2 mg), Tween(r) 80 (59.2 mg), Transcutol(r) P
      (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite(r)
      PS-10 (119.1 mg) and Vivapur(r) 105 (105.6 mg) as solid carriers, VST-loaded
      solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which
      possessed good flow properties and rapid drug dissolution. By introducing
      croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were
      also successfully formulated, which showed fast disintegration and high
      dissolution efficiency. Preparation of granules and tablets was successfully
      optimized using D-optimal mixture design and 3-level factorial design,
      respectively, resulting in percentage prediction errors of <10%. In
      pharmacokinetic studies in rats, the relative bioavailability of the optimized
      granules was 107% and 222% of values obtained for SuSMEDDS and Diovan(r) powder,
      respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer
      great potential for developing solid dosage forms of a liquefied formulation such
      as SuSMEDDS, while improving oral absorption of drugs with poor water solubility.

PMID- 29212230
TI  - MALAT1-miR-101-SOX9 feedback loop modulates the chemo-resistance of lung cancer
      cell to DDP via Wnt signaling pathway.
AB  - Cisplatin (DDP)-based chemotherapy is a standard strategy for lung cancer, while
      chemoresistance remains a major therapeutic challenge. Recent evidence highlights
      the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology.
      Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has important
      roles in regulating the proliferation, invasion and migration of lung cancer
      cell. High MALAT1 expression in lung cancer was related to poorer
      clinicopathologic features in this study. MALAT1 knockdown alone was sufficient
      to amplify DDP-induced repression of cell viability. MALAT1 knockdown could also
      sensitized DDP-resistant lung cancer cells (A549/DDP and H1299/DDP) to DDP.
      Further assays indicated that MALAT1 acted as a competing endogenous RNA to
      upregulate SOX9 expression by sponging miR-101 in DDP-resistant cancer cells,
      through Wnt signaling pathway. Moreover, SOX9 could bind to the promoter of
      MALAT1 to activate its transcription. Taken together, MALAT1, miR-101 and SOX9
      form a feedback loop to enhance the chemo-resistance of lung cancer cell to DDP;
      this MALAT1-miR-101-SOX9 feedback loop plays an important role in the chemo
      resistance of lung cancer cell to DDP and may serve as a potential target for
      cancer treatment.

PMID- 29212231
TI  - ZBP-89 function in colonic stem cells and during butyrate-induced senescence.
AB  - ZBP-89 (Zfp148, ZNF148) is a Kruppel-type zinc-finger family transcription factor
      that binds to GC-rich DNA elements. Earlier studies in cell lines demonstrated
      that ZBP-89 cooperates with Wnt beta-catenin signaling by inducing beta-catenin
      gene expression. Since beta-catenin levels are normally highest at the crypt
      base, we examined whether ZBP-89 is required for stem cell maintenance. Lineage
      tracing using a Zfp148CreERT2 transgenic line demonstrated expression in both
      intestine and colonic stem cells. Deleting the Zfp148 locus in the colon using
      the Cdx2NLSCreERT2 transgene, reduced the size and number of polyps formed in the
      Apc-deleted mice. Since colon polyps form in the presence of butyrate, a short
      chain fatty acid that suppresses cell growth, we examined the direct effect of
      butyrate on colon organoid survival. Butyrate induced senescence of colon
      organoids carrying the Apc deletion, only when Zfp148 was deleted. Using
      quantitative PCR and chromatin immunoprecipitation, we determined that butyrate
      treatment of colon cell lines suppressed ZNF148 gene expression, inducing CDKN2a
      (p16Ink4a ) gene expression. Collectively, Zfp148 mRNA is expressed in CBCs, and
      is required for stem cell maintenance and colonic transformation. Butyrate
      induces colonic cell senescence in part through suppression of ZBP-89 gene
      expression and its subsequent occupancy of the CDKN2A promoter.

PMID- 29212232
TI  - The effects of FK1706 on nerve regeneration and bladder function recovery
      following an end-to-side neurorrhaphy in rats.
AB  - Background: Immunophilin ligands are neuroregenerative agents binding to FK506
      binding proteins, by which stimulate recovery of neurons in a variety of injury
      nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and
      neuroregenerative effects but without immunosuppressive activity. At present,
      most reports about FK1706 in ameliorating nerve injury and functional recovery
      are limited to cavernous nerve injury and erectile function recovery. This study
      aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder
      function recovery following an end-to-side neurorrhaphy in rat models. Method:
      The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve
      (PPN) in the three groups' rats (FK1706 + ETS, ETS and control groups) were
      evaluated. Their intravesical pressure (IVP), S100beta and growth associated
      protein 43 (GAP43) expressions were also compared. Results: In FK1706 + ETS
      group, 90% the rats showed that the frequency of FG labeled neurons was larger
      than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB
      double-labeled neurons was larger than the 5.5 cutoff value. The average maximum
      of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their
      average number of myelinated axons of regenerated PPN reached 80% of the amount
      in control group. The nerve regeneration-associated markers data indicated that
      the expression level of S100beta and GAP43 in FK1706 + ETS group was
      approximately 2-fold higher than that of ETS group (P < 0.05). Conclusions: After
      end-to-side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and
      bladder function recovery.

PMID- 29212233
TI  - LncRNA XIST acts as a tumor suppressor in prostate cancer through sponging miR
      23a to modulate RKIP expression.
AB  - Accumulating evidences have indicated that aberrant expression of long non-coding
      RNAs (LncRNAs) is tightly associated with cancer development. Previous studies
      have reported that lncRNA XIST regulates tumor malignancies in several cancers.
      However, the underlying mechanism of XIST in prostate cancer remains unclear. In
      the current study, we found that XIST was down-regulated in prostate cancer
      specimens and cell lines. Low expression of XIST was correlated with poor
      prognosis and advanced tumor stage in prostate cancer patients. In gain and loss
      of function assays, we confirmed that XIST suppressed cellular proliferation and
      metastasis in prostate cancer both in vitro and in vivo. Furthermore, we found
      that XIST negatively regulates the expression of miR-23a and subsequently
      promotes RKIP expression at post-transcriptional level. Consequently, we
      investigated the correlation between XIST and miR-23a, and identified miR-23a as
      a direct target of XIST. In addition, over-expression of miR-23a efficiently
      abrogated the up-regulation of RKIP induced by XIST, suggesting that XIST
      positively regulates the expression of RKIP by competitively binding to miR-23a.
      Taken together, our study indicated that lncRNA XIST acts as a tumor suppressor
      in prostate cancer, and this regulatory effect of XIST will shed new light on
      epigenetic diagnostics and therapeutics in prostate cancer.

PMID- 29212234
TI  - Development and validation of a prognostic nomogram for IgA nephropathy.
AB  - IgA nephropathy (IgAN) shows strong heterogeneity between individuals. IgAN
      prognosis is associated with pathological lesions and clinical indicators.
      However, simple tools for evaluating the clinical prognosis remain inadequate.
      Our objective was to develop an intuitive estimation tool for predicting the IgAN
      prognosis. 349 patients with IgAN at The Chinese People's Liberation Army General
      Hospital were retrospectively analyzed from data between 2000 and 2006. A
      nomogram was developed using COX regression coefficients to predict decline of
      estimate Glomerular filtration rate (eGFR) >= 50% and end-stage renal disease
      (ESRD). The discriminative ability and predictive accuracy of the nomogram was
      determined via concordance index (C-index) and calibration curve. The results
      were verified in an independent validation cohort. In the derivation cohort, the
      nomogram was developed using mesangial hypercellularity, tubular
      atrophy/interstitial fibrosis, average proteinuria (A-P), and average mean
      arterial pressure (A-MAP) during hospitalization. The C-index of the nomogram was
      0.88 (95% CI, 0.80 to 0.96). The calibration curve showed good agreement between
      prediction and actual observation. Furthermore, the nomogram demonstrated good
      discrimination (C-index = 0.87, 95% CI 0.78 to 0.95) and calibration in the
      validation cohort. The nomogram could predict the prognosis of IgAN effectively
      and intuitively.

PMID- 29212235
TI  - AGER rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in
      metastatic lung adenocarcinoma.
AB  - Background: The receptor for advanced glycation end-product (RAGE) is a multi
      ligand receptor involved in inflammation. In the gene encoding RAGE (AGER), there
      are three well-known polymorphisms; rs2070600, rs1800624, and rs1800625, which
      potentially increase the risk of lung cancer. Remarkably, AGER rs2070600
      polymorphism, which increases ligand-binding affinity, is a potential prognostic
      factor in non-small cell lung cancer, but the underlying mechanism is unclear.
      The neutrophil-lymphocyte ratio (NLR) reflects tumor-associated systemic
      inflammatory conditions; high ratios are associated with poor prognosis in
      multiple cancers. Additionally, some humoral factors via RAGE-signaling are
      associated with elevated NLR in cancer patients. Objectives: Associations of AGER
      polymorphisms with disease susceptibility, prognosis, and NLR were investigated
      in Japanese patients with lung adenocarcinoma. Methods: We included 189 patients
      with lung adenocarcinoma, 96 of which had distant metastases, and 303 healthy
      controls. The correlation between AGER polymorphisms (rs2070600, rs1800624,
      rs1800625) and disease susceptibility and factors elevating the mortality and NLR
      in patients with metastases were evaluated. Results: Only the minor allele of
      rs2070600 was associated with a higher NLR (beta = 0.209, p = 0.043) and a poor
      prognosis (Hazard ratio = 2.06, 95% Confidence interval = 1.09-3.77, p = 0.028)
      in patients with metastatic disease, independently of background characteristics,
      including EGFR mutation status. All three polymorphisms were not associated with
      the risk of lung adenocarcinoma. Conclusions: The AGER rs2070600 polymorphism was
      independently associated with systemic inflammation and poor prognosis in
      patients with metastatic lung adenocarcinoma.

PMID- 29212236
TI  - Growth differentiation factor 15 mediates epithelial mesenchymal transition and
      invasion of breast cancers through IGF-1R-FoxM1 signaling.
AB  - Expression of the inflammatory cytokine growth differentiation factor 15 (GDF15)
      is significantly elevated in many tumor types in association with epithelial
      mesenchymal transition (EMT), drug resistance, and progressive disease. However,
      few studies have examined GDF15 expression, signaling, or function in breast
      cancer. In the current study, we demonstrate that GDF15 is associated with high
      tumor grade, ER-negativity, and HER2 overexpression in patients with breast
      cancer. Stable overexpression of GDF15 upregulates expression of mesenchymal
      markers and transcription factors, including FoxM1, and increases cellular
      invasion. GDF15 stable clones and breast cancer cells stimulated with recombinant
      human GDF15 (rhGDF15) demonstrate activation of insulin-like growth factor-1
      receptor (IGF-1R), EMT, and invasion. Pharmacologic inhibition of IGF-1R reduces
      GDF15-mediated EMT and invasion in stable clones, and FoxM1 knockdown rescues
      invasion and EMT in GDF15 stable clones and rhGDF15-stimulated cells. These data
      suggest that IGF-1R-FoxM1 signaling is a potential mechanism through which GDF15
      drives EMT and invasion of breast cancers. Further, GDF15 knockdown significantly
      inhibits invasion of HER2-overexpressing and triple-negative breast cancer cells,
      supporting further preclinical investigation of GDF15-targeted therapies.

PMID- 29212237
TI  - Association of type 2 diabetes mellitus and ratio of transmitral E wave velocity
      to early diastole mitral velocity with cardiovascular events in chronic kidney
      disease.
AB  - The association between DM and left ventricular diastolic dysfunction, assessed
      using the ratio of peak early transmitral filling wave velocity (E) to early
      diastolic velocity of mitral annulus (Ea), with cardiovascular (CV) outcomes in
      patients with chronic kidney disease (CKD) remains uncertain. This study included
      356 CKD stage 3-5 patients underwent echocardiography. All patients were
      classified into four groups based on the presence of DM and E/Ea <= or > 9. CV
      events included CV death, hospitalization for heart failure, unstable angina or
      nonfatal myocardial infarction, sustained ventricular arrhythmia, transient
      ischemic attack, and stroke. There were 58 CV events during the mean observation
      period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs. a
      combination of non-DM and E/Ea <= 9) was associated with CV events in unadjusted
      model (hazard ratio [HR], 6.990; 95% confidence interval [CI], 2.753-17.744; p <
      0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088-7.177; p =
      0.025). In the patients without DM, the E/Ea ratio (p = 0.033) improved the
      prediction of CV events, compared to the E/Ea ratio (p = 0.018), left atrial
      diameter (p = 0.016) and left ventricular mass index (p = 0.001) in the patients
      with DM. The combination of DM and left ventricular diastolic dysfunction was
      associated with CV events in patients with CKD stage 3-5. Assessments of DM
      status and E/Ea ratio may facilitate identifying high-risk patient population of
      unfavorable CV outcomes.

PMID- 29212238
TI  - Quantification of circulating cell-free DNA to predict patient survival in non
      small-cell lung cancer.
AB  - We used computed tomography (CT) to explore the prognostic value of cell-free
      (cf) DNA quantification and its predictive efficacy over time after chemotherapy
      in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were
      enrolled in a prospective biomarker trial. Consecutive paired blood collection
      was performed to determine cfDNA concentrations at baseline CT and throughout
      serial follow-ups. The best cfDNA cut-off value to predict progression-free and
      overall survival was determined using X-tile analysis. Among 112 chemo-naive
      patients with stage IV adenocarcinoma, 43 were available for follow-up analysis.
      Cox regression multivariate analysis indicated that a high cfDNA concentration
      was an independent negative prognostic factor for progression-free survival
      (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall
      survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001).
      However, cfDNA concentration changes during treatment did not correlate with
      radiological CT responses at first follow-up or best response. No pattern was
      noted in the percent change in the cfDNA concentration from baseline or
      subsequently measured level to progression. The serum cfDNA concentration is thus
      associated with NSCLC patient prognosis, but does not appear to be a clinically
      valid marker for tumor responses.

PMID- 29212239
TI  - Effects of lentivirus-mediated endostatin on endothelial progenitor cells.
AB  - Endothelial progenitor cells (EPCs) are candidates for gene therapies against
      retinal neovascularization (NV). The aim of present study was to investigate the
      effects of endostatin transfection on EPC function. In the present study, the
      EPCs were infected with lentivirus overexpressing endostatin. The transfection
      effects of endostatin overexpression on the proliferation, migratory,
      differentiation, apoptosis and the cell cycle of this cell line were determined.
      The real-time quantitative polymerase chain reaction (RT-qPCR) and western blot
      assays showed high expression levels of endostatin. A cell counting kit-8 assay
      showed that endostatin overexpression inhibited EPC proliferation. The transwell
      assay indicated that endostatin overexpression could suppress EPC migration.
      Furthermore, endostatin overexpression enhanced apoptosis (as showed by AnnexinV
      FITC/propidiumiodide staining analysis), induced differentiation and blocked the
      cell cycle. As compared with negative control group, EPC viability significantly
      decreased in gene transfection group. In conclusion, present study determined the
      feasibility of lentivirus-mediated endostatin gene transfer, and indirectly
      proved the effect of endostatin secretion on EPCs. Also our study provided a new
      opportunity for the potential application of gene therapy in retinal NV.

PMID- 29212240
TI  - LDB2 inhibits proliferation and migration in liver cancer cells by abrogating
      HEY1 expression.
AB  - Hepatocellular carcinoma (HCC) was one of the most common cancers around the
      world, has very low 5-year survival rate. However, the mechanism of HCC
      occurrence and development is largely unknown. LDB2 belongs to the LIM-domain
      binding family and functions as an adaptor for transcriptional regulation. Here
      we found that LDB2 is downregulated in HCC samples. LDB2 has the ability to
      inhibit proliferation and migration of hepatocarcinoma cells. We found that the
      proliferation and migration abilities in HCC sample cells were impaired after
      LDB2 overexpression and vice versa. In mechanism, we found that LDB2 can recruit
      BRD7 to HEY1 promoter and then block its expression. HEY1 whose expression is
      upregulated in HCC acts as an oncogene. In brief, our research reveals a new
      regulatory mechanism for hepatocarcinoma cell proliferation and migration.

PMID- 29212241
TI  - Prognostic group stratification and nomogram for predicting overall survival in
      patients who received radiotherapy for abdominal lymph node metastasis from
      hepatocellular carcinoma: a multi-institutional retrospective study (KROG 15-02).
AB  - Objective: To develop a prognostic model for overall survival (OS) in
      hepatocellular carcinoma (HCC) patients receiving radiotherapy (RT) to metastatic
      abdominal lymph nodes (LNs). Materials and Methods: Two hundred twenty-eight
      patients treated with RT to metastatic abdominal LNs were retrospectively
      reviewed. Results: Median OS in all patients was 11.1 months. LN responders had
      significantly higher median OS than non-responders (14.2 months vs. 7.5 months,
      p<0.05). On multivariate analysis, Child-Pugh classification, status of
      intrahepatic tumor, presence of distant metastasis, number and location of
      metastatic LNs, serum level of alpha fetoprotein (AFP), and the LN response to RT
      were significant prognostic factors for OS (p < 0.05 each). Based on the results
      of multivariate analysis, prognostic group stratification according to the number
      of pre-treatment risk factors was a significant predictor of OS, and median OS in
      patients with >= 4, 3, 2, 1, and 0 risk factors were 2.9, 5.5, 10.3, 13.6, and
      27.8 months, respectively (p<0.05). A nomogram was formulated by integrating the
      different prognostic contribution of each factor, and it showed good accuracy for
      predicting 2-year OS with a concordance index of 0.72. Conclusion: Prognostic
      group stratification and nomogram could be useful prognostic and therapeutic
      indicators in selecting treatment strategies.

PMID- 29212243
TI  - Effects of silencing Rab27a gene on biological characteristics and
      chemosensitivity of non-small cell lung cancer.
AB  - Rab27a, a member of the Rab protein family, can regulate the tumor
      microenvironment and promote the development of the tumor. Elevated expression of
      Rab27a is closely connected with many human cancers containing non-small cell
      lung cancer (NSCLC). But the role of Rab27a in non-small cell lung cancer and its
      possible mechanism is particularly unclear. In this research, we explored the
      effect of silencing Rab27a in vitro and in vivo, furnishing evidence that Rab27a
      could be a potential therapeutic target in NSCLC. Compared with corresponding
      control cells, silencing Rab27a had decreased ability of cell proliferation,
      migration and invasion in vitro and slower growth of xenograft tumors in mice.
      The expressions of apoptosis-associated proteins were induced with a reduction of
      anti-apoptotic protein in the NSCLC cells down-regulated Rab27a. Furthermore,
      Rab27a was associated with resistance to conventional chemotherapeutic agents.
      Our findings suggested that Rab27a might play a critical role in increasing
      chemosensitivity in NSCLC.

PMID- 29212242
TI  - Bovine herpesvirus 1 tegument protein UL21 plays critical roles in viral
      secondary envelopment and cell-to-cell spreading.
AB  - Bovine herpesvirus 1 (BoHV-1) UL21 is a tegument protein thought to be
      indispensable for efficient viral growth but its precise function in BoHV-1 is
      currently unknown. To determine the function of UL21 in BoHV-1 replication, we
      constructed a mutant virus bearing a UL21 deletion (vBoHV-1-?UL21) and its
      revertant virus, vBoHV-1-?UL21R, in which the UL21 gene was restored using a
      bacterial artificial chromosome system. The replication of vBoHV-1-?UL21 was
      1,000-fold lower and its plaque size was 85% smaller than those of the wild-type
      virus (BoHV-1). An ultrastructural analysis showed that deletion of UL21 led to
      an un-enveloped capsid accumulation in the cytoplasm, whereas nucleocapsid egress
      was not impaired, suggesting that UL21 is critical for secondary envelopment in
      BoHV-1. Co-immunoprecipitation assays revealed that HA-tagged UL21 pulled down
      UL16, suggesting that these two proteins form a complex, and this was further
      confirmed by a co-immunofluorescence assay. Taken together, these data provide
      evidence that UL21 plays critical roles in BoHV-1 secondary envelopment, and UL16
      is likely to be involved in these activities.

PMID- 29212244
TI  - Identification of potential prognostic ceRNA module biomarkers in patients with
      pancreatic adenocarcinoma.
AB  - Accumulating evidence suggested that long non-coding RNAs (lncRNAs) can function
      as competing endogenous RNAs (ceRNAs) to interact with other RNA transcripts and
      ceRNAs perturbation play important roles in cancer initiation and progression
      including pancreatic adenocarcinoma (PAAD). In this study, we constructed a PAAD
      specific hallmark gene-related ceRNA network (HceNet) using paired genome-wide
      expression profiles of mRNA, lncRNA and miRNA and regulatory relationships
      between them. Based on "ceRNA hypothesis", we analyzed the characteristics of
      HceNet and identified a ceRNA module comprising of 29 genes (12 lncRNAs, two
      miRNAs and 15 mRNAs) as potential prognostic biomarkers related to overall
      survival of patients with PAAD. The prognostic value of ceRNA module biomarkers
      was further validated in the train (Hazard Ratio (HR) =1.661, 95% CI: 1.275
      2.165, p<1.00e-4), test (HR=1.546, 95% CI: 1.238-1.930, p<1.00e-4), and entire
      (HR=1.559, 95% CI: 1.321-1.839, p<1.00e-4) datasets. Our study provides candidate
      prognostic biomarkers for PAAD and increases our understanding of ceRNA-related
      regulatory mechanism in PAAD pathogenesis.

PMID- 29212245
TI  - RBR-type E3 ubiquitin ligase RNF144A targets PARP1 for ubiquitin-dependent
      degradation and regulates PARP inhibitor sensitivity in breast cancer cells.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1), a critical DNA repair protein, is
      frequently upregulated in breast tumors with a key role in breast cancer
      progression. Consequently, PARP inhibitors have emerged as promising therapeutics
      for breast cancers with DNA repair deficiencies. However, relatively little is
      known about the regulatory mechanism of PARP1 expression and the determinants of
      PARP inhibitor sensitivity in breast cancer cells. Here, we report that ring
      finger protein 144A (RNF144A), a RING-between-RING (RBR)-type E3 ubiquitin ligase
      with an unexplored functional role in human cancers, interacts with PARP1 through
      its carboxy-terminal region containing the transmembrane domain, and targets
      PARP1 for ubiquitination and subsequent proteasomal degradation. Moreover,
      induced expression of RNF144A decreases PARP1 protein levels and renders breast
      cancer cells resistant to the clinical-grade PARP inhibitor olaparib. Conversely,
      knockdown of endogenous RNF144A increases PARP1 protein levels and enhances
      cellular sensitivity to olaparib. Together, these findings define RNF144A as a
      novel regulator of PARP1 protein abundance and a potential determinant of PARP
      inhibitor sensitivity in breast cancer cells, which may eventually guide the
      optimal use of PARP inhibitors in the clinic.

PMID- 29212246
TI  - The interaction between NOLC1 and IAV NS1 protein promotes host cell apoptosis
      and reduces virus replication.
AB  - NS1 of the influenza virus plays an important role in the infection ability of
      the influenza virus. Our previous research found that NS1 protein interacts with
      the NOLC1 protein of host cells, however, the function of the interaction is
      unknown. In the present study, the role of the interaction between the two
      proteins in infection was further studied. Several analyses, including the use of
      a pull-down assay, Co-IP, western blot analysis, overexpression, RNAi, flow
      cytometry, etc., were used to demonstrate that the NS1 protein of H3N2 influenza
      virus interacts with host protein NOLC1 and reduces the quantity of NOLC1. The
      interaction also promotes apoptosis in A549 host cells, while the suppression of
      NOLC1 protein reduces the proliferation of the H3N2 virus. Based on these data,
      it was concluded that during the process of infection, NS1 protein interacts with
      NOLC1 protein, reducing the level of NOLC1, and that the interaction between the
      two proteins promotes apoptosis of host cells, thus reducing the proliferation of
      the virus. These findings provide new information on the biological function of
      the interaction between NS1 and NOLC1.

PMID- 29212247
TI  - A six-mRNA signature model for the prognosis of head and neck squamous cell
      carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC), one of the most common cancers
      with high morbidity and mortality rates worldwide, has a poor prognosis. The
      transcriptome sequencing data of 500 patients with HNSCC in the TCGA dataset were
      assessed to find biomarkers associated with HNSCC prognosis so as to improve the
      prognosis of patients with HNSCC. The patients were divided into the training and
      testing sets. A model of six mRNAs (FRMD5, PCMT1, PDGFA, TMC8, YIPF4, ZNF324B)
      that could predict patient prognosis was identified in the training set using the
      Cox regression analysis. According to this model, the patients were divided into
      high-risk and low-risk groups. The Kaplan-Meier analysis showed that the high
      risk group showed significantly shorter overall survival time compared with the
      low-risk group in both training and testing sets. The receiver operating
      characteristic analysis further confirmed high sensitivity and specificity for
      the model, which was more accurate compared with some known biomarkers in
      predicting HNSCC prognosis. Moreover, the model was applicable to patients of
      different ages, genders, clinical stages, tumor locations, smoking history, and
      human papillomavirus (HPV) status, as well as to microarray dataset. This model
      could be used as a novel biomarker for the prognosis of HNSCC and a significant
      tool for guiding the clinical treatment of HNSCC. The risk score acquired from
      the model might contribute to improving outcome prediction and management for
      patients with HNSCC, indicating its clinical significance.

PMID- 29212248
TI  - Impact of complement component 3/4/5 single nucleotide polymorphisms on renal
      transplant recipients with antibody-mediated rejection.
AB  - Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction
      in kidney transplantation. The complement system is considered to be associated
      with the generation of alloreative antibodies and donor-specific antibodies.
      However, the association of complement single nucleotide polymorphisms (SNPs)
      with ABMR still remained unclear. Blood samples of 199 renal transplant
      recipients containing 68 with ABMR and 131 with stable graft function were
      collected, and analyzed by next-generation sequencing with an established gene
      panel. High quality readout was obtained in 18 C3 SNPs, 9 C4 SNPs and 22 C5 SNPs.
      Concerning C3 gene polymorphisms, after being adjusted with age, sex and
      immunosuppressive protocols, rs10411506 and rs2230205 were found to be
      statistically associated with ABMR in dominant model (rs10411506: OR=2.73, 95%
      CIs: 1.16, 6.68, P=0.028; rs2230205: OR=2.52, 95% CIs: 1.07, 5.92, P=0.034);
      rs10411506, rs2230205 and rs2230201 were found different in HET model
      (rs10411506: OR=3.05, 95% CIs: 1.22, 7.64, P=0.017; rs2230205: OR=2.90, 95% CIs:
      1.20, 7.00, P=0.018; rs2230201: OR=2.41, 95% CIs: 1.03, 5.64, P=0.042). The
      linkage analysis showed relatively high linkage disequilibrium among these SNPs.
      In addition, no significant correlation was found between C4 SNPs, or C5 SNPs,
      and the development of ABMR. Our study firstly identified the two SNPs
      (rs10411506 and rs2230205) in C3 gene were statistically correlated with ABMR in
      kidney transplantation. These findings may have implications for the diagnosis
      and prevention of ABMR.

PMID- 29212249
TI  - Long non-coding RNA XIST promotes cell growth and metastasis through regulating
      miR-139-5p mediated Wnt/beta-catenin signaling pathway in bladder cancer.
AB  - Bladder cancer is one of the most common urological malignancy all over the
      world. Recently, long non-coding RNA (lncRNA) XIST has been identified as an
      oncogenic gene in several type of cancers. However, the expression level and
      functional role of XIST in bladder cancer remain largely unknown. In the present
      study, we found that XIST was significantly up-regulated in bladder cancer
      tissues and cell lines, and was correlated with poor prognosis of bladder cancer
      patients. Furthermore, XIST knockdown significantly inhibited bladder cancer cell
      growth and metastasis in vitro and tumor growth in vivo. We also demonstrated
      that XIST acted as a competing endogenous RNA for miR-139-5p and repression of
      miR-139-5p could restore the inhibitory effects on bladder cancer cells induced
      by XIST shRNA. In addition, we identified that Wnt1 was a direct target of miR
      139-5p, and XIST played the oncogenic role in bladder cancer by activating the
      Wnt/beta-catenin signaling pathway. Taken together, our study suggested that
      lncRNA XIST may serve as a prognostic biomarker and a potential therapeutic
      target for bladder cancer.

PMID- 29212250
TI  - Histone deacetylase inhibitors reduce differentiating osteoblast-mediated
      protection of acute myeloid leukemia cells from cytarabine.
AB  - The bone marrow microenvironment protects acute myeloid leukemia (AML) cells
      during chemotherapy and is a major factor in relapse. Here, we examined which
      type(s) of bone marrow cells are responsible for the relapse of AML following
      treatment with cytarabine (Ara-C), and we identified a means to inhibit this
      protection. To determine the protective cell type(s), AML cells were treated with
      Ara-C, and AML cell survival in the presence or absence of osteoblast lineage
      cells was assessed. Cultured AML cells and patient bone marrow isolates were each
      significantly protected from Ara-C-induced apoptosis by co-culture with
      differentiating osteoblasts. Moreover, pretreating differentiating osteoblasts
      with the histone deacetylase inhibitors (HDACi) vorinostat and panobinostat
      abrogated the ability of the differentiating osteoblasts to protect AML cells.
      Together, our results indicate that differentiating osteoblasts have the
      potential to promote residual AML in the bone marrow following standard
      chemotherapy and act via a mechanism requiring HDACi-sensitive gene expression.
      Using HDACi to target the leukemic microenvironment in combination with Ara-C
      could potentially improve treatment of AML. Moreover, other strategies for
      manipulating bone marrow osteoblasts may also help eradicate AML cells and reduce
      relapse.

PMID- 29212251
TI  - Low fT3 is associated with diminished health-related quality of life in patients
      with acute coronary syndrome treated with drug-eluting stent: a longitudinal
      observational study.
AB  - Acute coronary syndrome (ACS) patients with low triiodothyronine (T3) syndrome
      characterized by low free T3 (fT3) levels with normal thyroxine (T4) and thyroid
      stimulating hormone (TSH) have a higher rate of death. The impact of fT3 on
      Health related quality of life (HRQOL) in patients with ACS is still unknown. 528
      ACS patients treated with drug-eluting stent (DES) were included in this
      prospective, observational study. Patients were classified into low fT3 group
      (n=126) and normal fT3 group (n=402) according to serum fT3 level. Every patient
      was prospectively interviewed at baseline and 1 year following percutaneous
      coronary intervention (PCI). HRQOL was assessed with the use of the Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36). Low fT3 patients had
      poorer HRQOL than normal fT3 patients both at baseline and 1-year follow-up (all
      p<0.05). During 1-year follow-up, HRQOL scores for all patients were
      significantly higher than baseline. Low fT3 patients had lesser gains in physical
      functioning, bodily pain, general health, vitality, social functioning and role
      emotional (all p<0.05). Generally, low fT3 patients demonstrated less improvement
      in Physical Component Score (PCS) (p=0.008) and Mental Component Score (MCS)
      (p=0.001). The percentage of patients reaching MCID for PCS and MCS was lower in
      low fT3 group than that in normal fT3 group (p<0.001). Multivariate linear
      regression analyses showed that low level of fT3 was an independent risk factor
      for PCS and MCS improvements. In conclusion, a low fT3 level is a predictor of
      worse HRQOL improvement in ACS patients treated with DES.

PMID- 29212253
TI  - Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR-RAS
      MAPK signaling pathway.
AB  - Ataxin-1 (ATXN1) is a coregulator protein within which expansion of the
      polyglutamine tract causes spinocerebellar ataxia type 1, an autosomal dominant
      neurodegenerative disorder. Previously, we reported that ATXN1 regulates the
      epithelial-mesenchymal transition of cervical cancer cells. In the present study,
      we demonstrate that ATXN1 is involved in cervical cancer tumorigenesis by
      promoting the proliferation of human cervical cancer cells. Chromatin
      immunoprecipitation assays showed that ATXN1 bound to the promoter region within
      cyclin D1 and activated cyclin D1 transcription, resulting in cell proliferation.
      ATXN1 promoted cyclin D1 expression through the EGFR-RAS-MAPK signaling pathway.
      Mouse xenograft tumorigenicity assays showed that ATXN1 downregulation inhibited
      tumorigenesis in cervical cancer cell lines in nude mice. Human cervical cancer
      tissue microarrays and immunohistochemical techniques showed that ATXN1 was
      significantly upregulated in many such tissues. Our results suggest that ATXN1
      plays an important role in cervical cancer tumorigenesis and is a prognostic
      marker for cervical cancer.

PMID- 29212252
TI  - C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3
      signaling axis in breast cancer cells.
AB  - The CC motif chemokine receptor 1 (CCR1) has been implicated in tumor invasion
      and metastasis in numerous cancers. However, the detailed mechanism of CCR1
      upregulation in metastatic tumor cells is poorly understood. The aim of this
      study was to clarify the regulatory mechanism underlying transcriptional
      activation of the CCR1 gene in response to epidermal growth factor (EGF)
      stimulation in breast cancer cells. CCR1 was highly expressed in human breast
      invasive ductal carcinoma (IDC) compared to adjacent normal tissues. Upon EGF
      stimulation, CCR1 expression was upregulated at the transcriptional level.
      Promoter analysis showed that signal transducer and activator of transcription 3
      (STAT3) is necessary for EGF-induced CCR1 promoter activation, and STAT3
      silencing abrogated EGF-induced CCR1 transcription. Pharmacological inhibition
      and short hairpin RNA-mediated knockdown experiments showed that AKT-dependent
      mammalian target of rapamycin (mTOR) activation was involved in the
      phosphorylation of serine-727 of STAT3, which in turn stimulated the
      transcription of the CCR1 gene. In conclusion, the AKT-mTOR-STAT3 signaling axis
      contributes to EGF-induced CCR1 expression, which promotes invasion and
      metastasis in breast cancer cells. We propose that the AKT-mTOR-STAT3 axis is a
      potential therapeutic target for blocking the invasion and metastasis of breast
      cancers.

PMID- 29212254
TI  - Distinct mobilization of leukocytes and hematopoietic stem cells by CXCR4 peptide
      antagonist LY2510924 and monoclonal antibody LY2624587.
AB  - Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a critical role
      in mobilization and redistribution of immune cells and hematopoietic stem cells
      (HSCs). We evaluated effects of two CXCR4-targeting agents, peptide antagonist
      LY2510924 and monoclonal antibody LY2624587, on mobilizing HSCs and white blood
      cells (WBCs) in humans, monkeys, and mice. Biochemical analysis showed LY2510924
      peptide blocked SDF-1/CXCR4 binding in all three species; LY2624587 antibody
      blocked binding in human and monkey, with minimal activity in mouse. Cellular
      analysis showed LY2624587 antibody, but not LY2510924 peptide, down-regulated
      cell surface CXCR4 and induced hematological tumor cell death; both agents have
      been shown to inhibit SDF-1/CXCR4 interaction and downstream signaling. In animal
      models, LY2510924 peptide induced robust, prolonged, dose- and time-dependent WBC
      and HSC increases in mice and monkeys, whereas LY2624587 antibody induced only
      moderate, transient increases in monkeys. In clinical trials, similar
      pharmacodynamic effects were observed in patients with advanced cancer: LY2510924
      peptide induced sustained WBC and HSC increases, while LY2624587 antibody induced
      only minimal, transient WBC changes. These distinct pharmacodynamic effects in
      two different classes of CXCR4 inhibitors are clinically important and should be
      carefully considered when designing combination studies with immune checkpoint
      inhibitors or other agents for cancer therapy.

PMID- 29212255
TI  - Soluble epoxide hydrolase inhibitors, t-AUCB, regulated microRNA-1 and its target
      genes in myocardial infarction mice.
AB  - Purpose: Soluble epoxide hydrolase inhibitors (sEHIs) had been demonstrated to
      produce cardioprotective effects against ischemia-induced lethal arrhythmias, but
      the exact mechanisms remain unknown. The present study was designed to
      investigate whether the beneficial effects of sEHIs are related to regulation of
      microRNA-1, which was a proarrhythmic factor in the ischemic heart. Methods: A
      mousemyocardial infarction (MI) model was established by ligating the coronary
      artery. sEHI t-AUCB (0.2, 1, 5 mg/L in drinking-water) was administered daily
      seven days before MI. The incidence of arrhythmias was assessed by in vivo
      electrophysiologic studies. miR-1, KCNJ2 (encoding the K+ channel subunit
      Kir2.1), and GJA1 (encoding connexin 43 [Cx43]) mRNA were measured by real-time
      PCR; Kir2.1 and Cx43 protein were assessed by western blotting and
      immunohistochemistry. Results: We demonstrated that sEHIs reduced the myocardium
      infarct size and incidence of inducible arrhythmias in MI mice. Up-regulation of
      miR-1 and down-regulation of KCNJ2/Kir2.1 and GJA1/Cx43 mRNA/protein were
      observed in ischemic myocaridum, whereas administration of sEHIs produced an
      opposite effect. In addition, miR-1 overexpression inhibited expression of the
      target mRNA and their corresponding proteins, whereas t-AUCB reversed the
      effects. Our results further revealed that PI3K/Akt signaling pathway might
      participate in the negatively regulation of miR-1 by sEHi. Conclusions: We
      conclude that sEHIs can repress miR-1, thus stimulate expression of KCNJ2/Kir2.1
      and GJA1/Cx43 mRNA/protein in MI mice, suggesting a possible mechanism for its
      potential therapeutic application in ischemic arrhythmias.

PMID- 29212256
TI  - Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves
      mucosal lining in colitis associated cancer.
AB  - In colitis associated cancer (CAC), chronic inflammation exposes the epithelial
      mucosal defensive lining to inflammatory mediators such as cytokines and anti
      microbial peptides (AMPs) causing the dysbiosis of microbiota population and the
      dysregulation of immune response. Matrix Metalloproteinases (MMPs) are zinc
      dependent endopeptidases which mediate inflammation, tissue remodeling, and
      carcinogenesis. MMP9 is undetectable in healthy tissue, although highly
      upregulated during inflammation and cancer. We have previously shown that MMP9
      plays a protective role in CAC opposite to its conventional role of acute
      inflammation and cancer mediator. In this study, we investigated the mechanistic
      role of MMP9 in preserving the epithelial mucosal integrity to suppress the
      progression of tumor microenvironment in CAC. We used transgenic mice
      constitutively expressing MMP9 in colonic epithelium (TgM9) as an in vivo model
      and intestinal cell line CaCo2BBE as an in vitro model. We induced CAC with three
      cycles of dextran sodium sulfate (DSS). We observed that MMP9 expression in
      colonic epithelium maintains the microbiota. We also observed that MMP9 mediates
      pro-inflammatory cytokine levels and AMPs but suppresses IL-22 resulting in lower
      levels of REG3-g and S100A8 AMPs. We also found that MMP9 maintains an efficient
      barrier function and the integrity of tight junctions. We also observed increased
      levels of mucin and intestinal trefoil factor among TgM9 mice in CAC. We also
      found that MMP9 expressing CaCo2BBE cells had increased expressions of EGFR and
      nuclear transcription factor- specificity protein 1 (Sp1). These data imply that
      MMP9 acts as a tumor suppressor in CAC by sustaining the epithelial mucosal
      integrity due to the activation of EGFR-Sp1 signaling pathway.

PMID- 29212257
TI  - Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial
      to mesenchymal transition in ovarian cancer cells.
AB  - BIRC5 encodes the protein survivin, a member of the inhibitor of apoptosis
      family. Survivin is highly expressed in a variety of cancers but has very low
      expression in the corresponding normal tissues, and its expression is often
      associated with tumor metastasis and chemoresistance. We report that survivin was
      highly expressed in ovarian cancer and strongly correlated with patient overall
      poor survival. For the first time, we provide experimental evidence that survivin
      is involved in epithelial to mesenchymal transition (EMT) in ovarian cancer
      cells. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 gene editing led to
      the inhibition of EMT by upregulating epithelial cell marker, cytokeratin 7 and
      downregulating mesenchymal markers: snail2, beta-catenin, and vimentin in both
      ovarian cancer SKOV3 and OVCAR3 cells. Consistent with this molecular approach,
      pharmacological treatment of ovarian cancer cells using a small molecule survivin
      inhibitor, YM155 also inhibited EMT in these ovarian cancer cell lines.
      Overexpression of BIRC5 promoted EMT in SKOV3 cells. Using molecular or
      pharmacological approaches, we found that cell proliferation, migration, and
      invasion were significantly inhibited following BIRC5 disruption in both cell
      lines. Inhibition of BIRC5 expression also sensitized cell responses to
      paclitaxel treatment. Moreover, loss of BIRC5 expression attenuated TGFbeta
      signaling in both SKOV3 and OVCAR3 cells. Collectively, our studies demonstrated
      that disruption of BIRC5 expression inhibited EMT by attenuating the TGFbeta
      pathway in ovarian cancer cells.

PMID- 29212258
TI  - Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules.
AB  - [99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid
      nodules. However, there is a lack of evidence about the accuracy of this method
      in the European population. The aim of this study was to assess the utility of
      MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients
      underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol.
      Interpretation of the images included a scoring system from 0 (absent) to 3
      (increased); this was to provide a scale for the uptake of the thyroid nodule in
      comparison to the paranodular tissue. Additionally, we evaluated the tracer
      uptake trend in late images compared to early images. We used the final
      histopathology as the reference standard. Scores 0-1 in early images, scores 0-2
      in late images, and an absence of increasing uptake in the thyroid nodule in late
      images, showed the best predictive values to exclude malignancy, respectively
      (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant
      nodules was evident in early images with a score 1-3. Highest specificity (91%)
      was obtained when the negative was defined as an absence of uptake-increase, in
      the late images. This study confirms that the most valuable feature of MIBI is
      the high NPV. Thus, with the appropriate interpretation method, high sensitivity
      and specificity, and moderate PPV can be obtained.

PMID- 29212259
TI  - Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in
      rats with acute traumatic brain injury.
AB  - Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula,
      has been reported effective on traumatic brain injury (TBI) in rats. However, its
      cerebral protection mechanism has not been clarified at the metabolic level. This
      work aims to explore the global metabolic characteristics of XFZY in rats during
      the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas
      chromatography-mass spectrometry coupled with univariate analysis and
      multivariate statistical analysis was performed in three groups (Sham, Vehicle,
      XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to
      illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment
      attenuates neurological dysfunction and cortical lesion volume post-injury on day
      3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid,
      3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are
      mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and
      glutamate metabolism, and inositol phosphate metabolism. Our study reveals
      potential biomarkers and metabolic networks of acute TBI and neuroprotection
      effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be
      a feasible way to systematically study therapeutic effects of XFZY on TBI.

PMID- 29212260
TI  - Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer
      and P31 mesothelioma cells.
AB  - Acquired cisplatin resistance is a common feature of tumours following cancer
      treatment with cisplatin and also of non-small cell lung cancer (H1299) and
      mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular
      basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was
      undertaken. We demonstrate that cellular oxygen consumption was significantly
      decreased in cisplatin resistant cells and that the reduction was primarily due
      to reduced mitochondrial activity as a result of reduced mitochondrial abundance.
      The differential mitochondrial abundance was supported by data showing reduced
      sirtuin 1 (SIRT1), peroxisome-proliferator activator receptor-gamma co-activator
      1-alpha (PGC1alpha), sirtuin 3 (SIRT3) and mitochondrial transcription factor A
      (TFAM) protein expression in resistant cells. Consistent with these data we
      observed increased reactive oxygen species (ROS) production and increased hypoxia
      inducible factor 1-alpha (HIF1alpha) stabilization in cisplatin resistant cells
      when compared to cisplatin sensitive controls. We also observed an increase in
      AMP kinase subunit alpha2 (AMPKalpha2) transcripts and protein expression in
      resistant H1299 cells. mRNA expression was also reduced for cisplatin resistant
      H1299 cells in these genes, however the pattern was not consistent in resistant
      P31 cells. There was very little change in DNA methylation of these genes,
      suggesting that the cells are not stably reprogrammed epigenetically. Taken
      together, our data demonstrate reduced oxidative metabolism, reduced
      mitochondrial abundance, potential for increased glycolytic flux and increased
      ROS production in acquired cisplatin resistant cells. This suggests that the
      metabolic changes are a result of reduced SIRT3 expression and increased HIF
      1alpha stabilization.

PMID- 29212261
TI  - Cordycepin stimulates autophagy in macrophages and prevents atherosclerotic
      plaque formation in ApoE-/- mice.
AB  - Autophagy in macrophages plays a key role in the pathogenesis and progression of
      atherosclerosis and has become a potential therapeutic target. Here we show that
      cordycepin (Cpn), a natural derivative of adenosine, markedly reduced
      atherosclerotic plaque and ameliorated associated symptoms such as dyslipidemia,
      hyperglycemia and inflammation in ApoE-/- mice. Supplementation of Cpn dose
      dependently inhibited oxLDL-elicited foam cell formation and modulated
      intracellular cholesterol homeostasis by inhibiting cholesterol uptake and
      promoting cholesterol efflux in RAW264.7 macrophages. Notably, Cpn exhibited
      significant stimulating effect on macrophage autophagy, as estimated by western
      blotting, immunofluorescent staining and autophagic vacuoles observation by
      transmission electron microscopy. The inhibitive effects of Cpn on foam cell
      formation were dramatically deteriorated in the presence of various autophagy
      inhibitors, suggesting that autophagy participate, at least in part, in the
      atheroprotective role of Cpn. Further investigations using different autophagy
      inhibitors and specific siRNAs for AMP-activated protein kinase (AMPK) gamma1
      subunit indicated that Cpn may stimulate macrophage autophagy through AMPK-mTOR
      pathway. Together, our results demonstrated Cpn as a potential therapeutic agent
      for the prevention and treatment of atherosclerosis, and the autophagic activity
      presents a novel mechanism for Cpn-mediated atheroprotection.

PMID- 29212262
TI  - A missense variant in EZH2 is associated with colorectal cancer risk in a Chinese
      population.
AB  - Colorectal cancer (CRC) ranks the fifth leading cause of cancer death in China.
      EZH2 is a member of Polycomb-group (PcG) family and associated with
      transcriptional repression and cancer development. In this study, we report the
      association between a missense variant in EZH2 and risk of CRC. Through a
      systematic selection of variants in EZH2, we identified rs2302427 in the exon
      region of EZH2 and genotyped this variant in 852 CRC patients and 1,303 healthy
      controls using Taqman genotyping assay. The association between this variant and
      CRC risk was calculated using logistic regression with adjustment of sex, age,
      smoking status and drinking status. The result showed that rs2302427 was
      significantly associated with CRC susceptibility under an additive model
      (P=0.0068). Compared with CC genotype carriers, CG genotype and GG genotype
      carriers were associated with risk of CRC with odds ratio being 0.78 (95% CI:
      0.63-0.96, P=0.0198) and 0.54 (95% CI: 0.24-1.18, P=0.1224), respectively. When
      stratified by sex, age, smoking status or drinking status, significant
      associations were observed only in younger individuals (OR=0.67, 95% CI: 0.50
      0.89, P=0.0067) or smokers (OR=0.65, 95% CI: 0.48-0.88, P=0.0051). This study
      provides new insights into the personalized prevention of colorectal cancer.

PMID- 29212263
TI  - Combination of betulinic acid and chidamide inhibits acute myeloid leukemia by
      suppression of the HIF1alpha pathway and generation of reactive oxygen species.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic
      system with no common genetic "Achilles heel" that can be targeted. Most patients
      respond well to standard therapy, while a majority relapse, and development of an
      effective therapy for AML patients is still urgently needed. In this study, we
      demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon
      receptor (AHR) expression through demethylation on the AHR promoter in AML cells,
      and the increased AHR expression interacts with and sequesters ARNT, subsequently
      suppressing hypoxia-inducible factor-1alpha (HIF1alpha) pathway. We also found
      that histone deacetylase inhibitor chidamide (CDM) treatment significantly
      increased p300 over-acetylation in AML cells with dissociation of p300 with
      HIF1alpha, and subsequently suppressed the HIF1alpha pathway. Further
      investigation showed that BA/CDM combination additively increased generation of
      reactive oxygen species (ROS) with DNA damage, apoptosis and mitochondrial
      dysfunction. Also, BA/CDM combination additively suppressed the HIF1alpha pathway
      with decreased VEGF expression. in vivo mice study showed that BA/CDM combination
      significantly suppressed AML tumor growth, and overexpression of SOD2 and a
      constitutive HIF1alpha (HIF1C) completely diminished this effect. We conclude
      that a BA/CDM combination inhibits AML tumors through ROS over-generation and
      HIF1alpha pathway suppression. This is the first time we have shown the potential
      effect and possible mechanism of BA and CDM on the inhibition of AML tumor
      growth.

PMID- 29212264
TI  - CR6-interacting factor 1 inhibits invasiveness by suppressing TGF-beta-mediated
      epithelial-mesenchymal transition in hepatocellular carcinoma.
AB  - CR6-interacting factor 1 (CRIF1) regulates cell cycle progression and the DNA
      damage response. Here, we show that CRIF1 expression is decreased in
      hepatocellular carcinoma (HCC) tissues and positively correlates with patients'
      survival. In vitro, down-regulation of CRIF1 promotes HCC cell proliferation and
      invasiveness, while over-expression has the opposite effect. in vivo, CRIF1
      knockdown enhances growth of HCC xenografts. Analysis of mRNA microarrays showed
      that CRIF1 knockdown activates genes involved in TGF-beta RI/Smad2/3 signaling,
      leading to epithelial-mesenchymal transition (EMT) and increased matrix
      metalloproteinase-3 (MMP3) expression. However, cell invasion and EMT are
      abrogated in HCC cells treated with SB525334, a specific TGF-beta RI inhibitor,
      which indicates the inhibitory effect of CRIF1 on HCC tumor growth is mediated by
      TGF-beta signaling. These results demonstrate that CRIF1 benefits patient
      survival by inhibiting HCC cell invasiveness through suppression of TGF-beta
      mediated EMT and MMP3 expression. This suggests CRIF1 may serve as a novel target
      for inhibiting HCC metastasis.

PMID- 29212265
TI  - Systematic identification of long non-coding RNAs with cancer-testis expression
      patterns in 14 cancer types.
AB  - Cancer-testis (CT) genes are a group of genes that are potential targets of
      immunotherapy and candidate epi-drivers participating in the development of
      cancers. Previous studies mainly focused on protein-coding genes, neglecting long
      non-coding RNAs with the same expression patterns. In this study, we performed a
      systematic investigation of cancer-testis long non-coding RNAs (CT-lncRNAs) with
      multiple independent open-access databases.We identified 1,325 extremely highly
      expressed CT-lncRNAs (EECT-lncRNAs) in 14 cancer types. Functional annotation
      revealed that CT-lncRNAs reactivated in cancers could promote genome instability
      and the malignant potential of cancers. We observed a mutually exclusive pattern
      of EECT-lncRNA activation and mutation in known oncogenes, suggesting their
      potential role as drivers of cancer that complement known mut-driver genes.
      Additionally, we provided evidence that testis-specific regulatory elements and
      promoter hypo-methylation may be EECT-lncRNA activation mechanisms, and EECT
      lncRNAs may regulate CT gene reactivation. Taken together, our study puts forth a
      new hypothesis in the research field of CT genes, whereby CT-lncRNAs/EECT-lncRNAs
      play important roles in the progression and maintenance of tumorigenesis,
      expanding candidate CT epi-driver genes from coding genes to non-coding RNAs.

PMID- 29212267
TI  - Development of diagnostic model of lung cancer based on multiple tumor markers
      and data mining.
AB  - Objective: To develop early intelligent discriminative model of lung cancer and
      evaluate the efficiency of diagnosis value. Methods: Based on the genetic
      polymorphism profile of CYP1A1-rs1048943, GSTM1, mEH-rs1051740, XRCC1-rs1799782
      and XRCC1-rs25489 and the methylations of p16 and RASSF1A gene, and the length of
      telomere in the peripheral blood from 200 lung cancer patients and 200 health
      persons, the discriminative model was established through decision tree and ANN
      technique. Results: ACU of the discriminative model based on multiple tumour
      markers increased by about 10%; The accuracy rate of decision tree model and ANN
      model for testing set were 93.00% and 89.62% respectively. The ROC analysis
      showed the decision tree model's AUC is 0.929 (0.894~0.964), the ANN model's AUC
      is 0.894 (0.853~0.935). However, the classify accuracy rate and AUC of Fisher
      discriminatory analysis model are all about 0.7. Conclusion: The early
      intelligent discriminative model of lung cancer based on multiple tumor markers
      and data mining techniques has a higher accuracy rate and might be useful for
      early diagnosis of lung cancer.

PMID- 29212268
TI  - COMP-angiopoietin-1 mitigates changes in lipid droplet size, macrophage
      infiltration of adipose tissue and renal inflammation in streptozotocin-induced
      diabetic mice.
AB  - Adipose tissue is considered to be an endocrine organ, and adipocyte size
      correlates with insulin resistance and metabolic parameters in obesity. There is
      little data on the effects of angiopoietin-1 in adipose tissue and kidney in
      streptozotocin (STZ)-induced diabetes. In this study, we investigated the
      protective effect of COMP-angiopoietin-1 (COMP-Ang1), a potent variant of
      angiopoietin-1, on vascular endothelial cells in epididymal adipose tissue and
      its regulatory effect on other metabolic parameters, such as lipid droplet
      diameter, macrophage infiltration, and renal inflammation in STZ-treated mice.
      Our data showed that COMP-Ang1 increased the density of platelet endothelial cell
      adhesion molecule-1 (PECAM-1)-1-positive vascular endothelial cells in adipose
      tissue, which were significantly decreased by treatment with STZ. COMP-Ang1
      ameliorated the STZ-induced decrease in lipid droplet diameter and increase in
      macrophage infiltration in adipose tissue. Serum free fatty acid and triglyceride
      levels were decreased after administration of COMP-Ang1. There was a beneficial
      effect on serum insulin levels after treatment with COMP-Ang1 in STZ-induced
      diabetic mice. Fasting blood glucose levels in COMP-Ang1-treated mice were
      significantly lower than those of LacZ-treated mice. Cotreatment with COMP-Ang1
      and STZ also had similar effects on the above parameters. Administration of
      soluble Tie2, an inhibitor of angiopoietin-1, reversed the effects of COMP-Ang1.
      COMP-Ang1 was found to ameliorate the up-regulation of proinflammatory molecules
      and F4/80-positive macrophage infiltration in the kidneys of STZ-treated mice.
      COMP-Ang1 increased the phosphorylation of Akt in epididymal adipose tissue and
      kidneys of STZ-induced diabetic mice. These data indicate that COMP-Ang1
      regulates lipogenic effects in adipose tissue and renal inflammation in STZ
      induced diabetic mice.

PMID- 29212266
TI  - EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279 inhibits growth of
      neuroblastoma.
AB  - Treatment failure in high risk neuroblastoma (NB) is largely due to the
      development of chemotherapy resistance. We analyzed the gene expression changes
      associated with exposure to chemotherapy in six high risk NB tumors with the aid
      of the Connectivity Map bioinformatics platform. Ten therapeutic agents were
      predicted to have a high probability of reversing the transcriptome changes
      associated with neoadjuvant chemotherapy treatment. Among these agents, initial
      screening showed the EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279,
      had obvious cytotoxic effects on NB cell lines. Using a panel of NB cell lines,
      including MYCN nonamplified (SK-N-AS, SH-SY5Y, and CHLA-255), and MYCN amplified
      (NB-19, NGP, and IMR-32) cell lines, we found that YK-4-279 had cytotoxic effects
      on all lines tested. In addition, YK-4-279 also inhibited cell proliferation and
      anchorage-independent growth and induced cell apoptosis of these cells. YK-4-279
      enhanced the cytotoxic effect of doxorubicin (Dox). Moreover, YK-4-279 was able
      to overcome the established chemoresistance of LA-N-6 NB cells. In an orthotopic
      xenograft NB mouse model, YK-4-279 inhibited NB tumor growth and induced
      apoptosis in tumor cells through PARP and Caspase 3 cleavage in vivo. While EWS
      FLI1 fusion protein is not frequently found in NB, using the R2 public database
      of neuroblastoma outcome and gene expression, we found that high expression of
      EWSR1 was associated with poor patient outcome. Knockdown of EWSR1 inhibited the
      oncogenic potential of neuroblastoma cell lines. Taken together, our results
      indicate that YK-4-279 might be a promising agent for treatment of NB that merits
      further exploration.

PMID- 29212269
TI  - Low neighbor of Brca1 gene expression predicts poor clinical outcome and
      resistance of sunitinib in clear cell renal cell carcinoma.
AB  - Objective: To study the expression of Neighbor of Brca1 gene (NBR1) in clear cell
      renal cell carcinoma (ccRCC), renal cancer cells and the chemoresistance cells
      and to elucidate its clinical prognostic and chemoresistance value. Materials and
      Methods: We screened the NBR1 mRNA in ccRCC from The Cancer Genome Atlas (TCGA)
      database and examined expression levels of NBR1 mRNA in 48 cases of ccRCC
      tissues, renal cancer cell lines and chemoresistance cells by qRT-PCR. Then, we
      extended two additional data sets in oncomine datebase (https://www.oncomine.org)
      to further confirm the results of the TCGA database. Immunohistochemistry (IHC)
      assay data performed in ccRCC tissues and normal tissues were downloaded from The
      Human Protein Atlas. Results: The mRNA levels of NBR1 were downregulated in TCGA
      KIRC database (n = 533) and ccRCC patient samples (n=48) as well as in RCC cell
      lines and their chemoresistance cells. Similarly, the protein levels of NBR1 were
      lower in ccRCC patient samples. NBR1 level was associated with the clinical
      pathological stage and could discriminate metastasis, recurrence and prognosis in
      ccRCC patients. Low level of NBR1 mRNA showed a significance poor prognostic of
      overall survival (OS), disease-free survival (DFS) with univariate and
      multivariate analyses in ccRCC patients and sunitinib resistance. Conclusions:
      Taken together, our results suggest that low level of NBR1 can predict poor
      clinical outcome and resistance of sunitinib in patients with ccRCC.

PMID- 29212270
TI  - Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic
      metastasis of prostate cancer.
AB  - Exosomes from cancer cells, which contain microRNA and reach metastasis loci
      prior to cancer cells, stimulate the formation of a metastatic microenvironment.
      Previous studies have shown that exosomal miR-141-3p is associated with
      metastatic prostate cancer (PCa). However, the role and regulatory mechanism of
      miR-141-3p in the microenvironment of bone metastases require further study. In
      this study, we performed a series of experiments in vivo and in vitro to
      determine whether exosomal miR-141-3p from MDA PCa 2b cells regulates osteoblast
      activity to promote osteoblastic metastasis. We demonstrate that extracts
      obtained from cell culture supernatants contained exosomes and that miR-141-3p
      levels were significantly higher in MDA PCa 2b cell exosomes. Via confocal
      imaging, numerous MDA PCa 2b exosomes were observed to enter osteoblasts, and miR
      141-3p was transferred to osteoblasts through MDA PCa 2b exosomes in vitro.
      Exosomal miR-141-3p from MDA PCa 2b promoted osteoblast activity and increased
      osteoprotegerin OPG expression. miR-141-3p suppressed the protein levels of the
      target gene DLC1, indicating its functional significance in activating the
      p38MAPK pathway. In animal experiments, exosomal miR-141-3p had bone-target
      specificity and promoted osteoblast activity. Mice injected with miR-141-3p
      mimics exosomes developed apparent osteoblastic bone metastasis. Exosomal miR-141
      3p from MDA PCa 2b cells promoted osteoblast activity and regulated the
      microenvironment of bone metastases, which plays an important role in the
      formation of bone metastases and osteogenesis damage in PCa. Clarifying the
      specific mechanism of bone metastasis will help generate new possibilities for
      the treatment of PCa.

PMID- 29212271
TI  - Inhibition of astrocytic activity alleviates sequela in acute stages of
      intracerebral hemorrhage.
AB  - Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within
      the first 24 hours. Together with the microglia/macrophages (MMPhi), astrocytes
      are important cell population responsible for many brain injuries but rarely
      being highlighted in acute stage of ICH. In present study, we induced rats ICH
      either by collagenase or autologous blood injection. Experimental groups were
      classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5
      (trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each
      group). MRI assessments after ICH were used to evaluate the hematoma progression
      and blood-brain barrier (BBB) integrity. The glia cells accumulations were
      examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes
      but few MMPhi were observed in hyperacute and acute ICH. Upon suppression of
      astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less
      BBB destruction, reduced astrocyte accumulation in perihematomal regions,
      postponed course of hemoresolution and gain better outcomes. These finding
      provide evidence that activated astrocytes are crucial cell populations in
      hyperacute and acute ICH, and their modulation may offer opportunities for novel
      therapy and patient management.

PMID- 29212272
TI  - Polymorphisms of rs1347093 and rs1397529 are associated with lung cancer risk in
      northeast Chinese population.
AB  - Lung cancer is one of the malignant tumors with the highest morbidity and
      mortality all over the world. Here we researched the association between two SNPs
      (rs1347093 in MIR217HG and rs1397529 in Gab1) and the risk of lung cancer in
      northeast Chinese population, including 825 cases and 766 controls. We carried
      out chi2 test, unconditional logistic regression analysis and crossover analysis
      to estimate the relationship between SNPs and lung cancer risk and the
      interaction between SNPs and smoking on susceptibility to lung cancer. The
      results indicated that rs1347093, rs1397529 polymorphisms were associated with
      lung cancer risk, especially with adenocarcinoma risk. Dominant genetic model of
      the rs1347093 was associated with reduced risk of lung cancer compared to CC
      genotype (AC+AA vs. CC: adjusted OR = 0.599, 95%CI = 0.418-0.858, P=0.005). For
      rs1347093, the similar result was found. Dominant genetic model of the rs1397529
      was associated with reduced risk of lung cancer compared to AA genotype (AC+CC
      vs. AA: adjusted OR = 0.664, 95%CI = 0.491-0.897, P=0.008). There is no
      significant interaction between rs1347093, rs1397529 polymorphism and smoking on
      susceptibility to lung cancer. Our study might demonstrate that rs1347093 in
      MIR217HG and rs1397529 in Gab1 could be meaningful as the novel biomarker for
      lung cancer risk.

PMID- 29212273
TI  - Repositioning CEP-1347, a chemical agent originally developed for the treatment
      of Parkinson's disease, as an anti-cancer stem cell drug.
AB  - CEP-1347 is a mixed lineage kinase inhibitor tested in a large-scale phase 2/3
      clinical trial in early Parkinson's disease, in which its safety and
      tolerability, but nevertheless not efficacy, was demonstrated. Here we identify
      by drug repositioning CEP-1347 as a potential anti-cancer stem cell drug. In
      vitro, CEP-1347 efficiently induced differentiation and inhibited the self
      renewal and tumor-initiating capacities of human cancer stem cells from
      glioblastoma as well as from pancreatic and ovarian cancers at clinically
      relevant concentrations, without impairing the viability of normal fibroblasts
      and neural stem cells. In vivo, a 10-day systemic administration of CEP-1347 at a
      dose that was less than 1/10 the mouse equivalent of the dose safely given to
      humans for 2 years was sufficient to effectively reduce tumor-initiating cancer
      stem cells within established tumors in mice. Furthermore, the same treatment
      protocol significantly extended the survival of mice receiving orthotopic
      implantation of glioma stem cells. Together, our findings suggest that CEP-1347
      is a promising candidate for cancer stem cell-targeting therapy and that further
      clinical and preclinical studies are warranted to evaluate its efficacy in cancer
      treatment.

PMID- 29212274
TI  - Extramural vascular invasion detected by contrast-enhanced multiple-row detectors
      computed tomography (ceMDCT) as a predictor of synchronous metastases in colon
      cancer.
AB  - Background: Extramural Vascular Invasion (EMVI) is histologically defined as the
      presence of tumor cells beyond the muscularis propria in vessels resulting in
      disease metastases. Objective: To determine whether EMVI, detected by contrast
      enhanced multiple-row detectors computed tomography (MDCT), has closely
      association with synchronous metastases in colon cancer. Methods: Patients with
      pathology proven colon cancer were included in this retrospective study.
      Preoperative imaging status, including Extramural tumor depth, Lymph nodes, tumor
      location, and ctEMVI status, were defined on MDCT. Postoperative pathological
      tumor stage, lymph node stage, and tumor differentiation, were defined in
      accordance with the American Joint Committee on Cancer (AJCC) 7th Edition.
      Synchronous metastases were detected on follow-up MDCT 3 months after initial
      diagnosis or by surgery, if available. Associations between ctEMVI and other
      preoperative and postoperative factors were analyzed using Chi-squared tests.
      Logistic regression analyses were performed to analyze the preoperative and
      postoperative factors of synchronous metastases in colon cancer. Results: ctEMVI
      was observed in 96 patients (96/241, 39.8%). The presence of ctEMVI varied
      significantly depending on ctEMD (chi2 = 66.557, P<0.001), lymph nodes status on
      MDCT (chi2 =24.533, P=0.001), pathological tumor status (chi2 = 36.267, P <0.001)
      and pathological lymph nodes status analyses (chi2 =32.103, P <0.001).
      Synchronous metastases were seen in 36 patients (36/96, 37.5%) with ctEMVI and 11
      (11/145, 7.6%) patients without ctEMVI. The incidence of synchronous metastases
      was significantly higher in the cohort of positive ctEMVI with odds ratio (OR) of
      7.309 (95% CI 3.485~15.330, P<0.001). Positive ctEMVI (Odds ratio 4.654, 95%CI:
      1.987~10.898, P <0.001) and ctEMD larger than 5 mm (Odds ratio 2.654, 95%CI:
      1.116~6.309, P =0.027) were demonstrated to be significant preoperative factors
      in predicting synchronous metastases. Conclusion: MDCT-detected EMVI could be
      used as a preoperative factor to predict synchronous metastases in colon cancer.

PMID- 29212275
TI  - Physical exercises and weight loss in obese patients help to improve uric acid.
AB  - Objective: to assess the impact of longitudinal change of the overweight and
      physical activity on hyperuricemia. Methods: We performed a retrospective cohort
      study. Demographic information, clinical features, laboratory findings, body
      weight and physical exercises pattern were documented. Results: Altogether 4678
      cases of hyperuricemia were enrolled. The median aged males were most affected.
      Individuals in the middle age had the highest prevalence of being overweight
      (2501/3382, 74.0%). Middle aged with BMI>=25 kg/m2 were more likely to lose
      weight (963/2807, 34.3%). BMI and waist circumference control helped to reduce
      serum uric acid. Overweight population was more likely to use urate-lowering or
      uricosuric medication (3025/3382, 89.4%). Intermediate and heavy activity were
      associated with bigger SUA improvement. Patients in the age of 35-60 were more
      likely to do physical exercises than the others. Conclusion: Being overweight is
      strongly associated with hyperuricemia. Successful weight control was correlated
      with significant uric acid reduction. Intermediate to heavy physical activity
      helps to reduce waist circumference and SUA. In the hyperuricemia population,
      obese, middle aged men were the most affected, and also the most likely to do
      more exercises and get their bodyweight back to normal.

PMID- 29212276
TI  - Low circulating levels of the mitochondrial-peptide hormone SHLP2: novel
      biomarker for prostate cancer risk.
AB  - Context: Mitochondrial DNA mutations and dysfunction are associated with prostate
      cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial
      encoded peptide and an important mitochondrial retrograde signaling molecule.
      Objective: To determine whether serum SHLP2 concentration is associated with PCa
      risk and whether associations are race-specific.Design, Setting and Participants:
      Patients undergoing prostate biopsy were recruited from the Durham Veterans
      Affairs hospital. Serum was collected prior to biopsy and SHLP2 measured by
      ELISA. We selected 200 men for analysis (100 negative biopsies and 100 PCa cases;
      100 black and 100 white). Results: Mean SHLP2 levels were significantly higher in
      white controls versus black controls and SHLP2 was significantly higher in white
      controls versus white PCa cases. In contrast, there was no significant difference
      in SHLP2 levels between black controls and black cases. SHLP2 levels > 350-pg/ml
      ruled out PCa with >= 95% accuracy in both races. Conclusions: Lower SHLP2 was
      linked with increased PCa risk in white men, but no significant association was
      observed in black men. While SHLP2 > 350-pg/ml ruled out PCa in both races with
      high accuracy, SHLP2 was unrelated to PCa grade. These data suggest the
      circulating mitochondrial-derived peptide hormone, SHLP2 plays a key role in the
      development and racial disparity of prostate cancer.

PMID- 29212277
TI  - Tumor necrosis factor-alpha -308 G/A polymorphism and risk of sepsis, septic
      shock, and mortality: an updated meta-analysis.
AB  - Background: The -308G/A polymorphism in the gene encoding tumor necrosis factor
      alpha (TNF-alpha) has been implicated in sepsis risk in many studies but with
      variable results. This study aimed to comprehensively assess the evidence of
      association between this polymorphism and risk of sepsis and sepsis-related
      mortality. Materials and Methods: PubMed, EMBASE and other databases were
      searched to identify relevant studies, and data were analyzed using Review
      Manager 5.0 and STATA 12.0. Results: Data from 34 publications involving 12,284
      subjects were meta-analyzed. Combined analysis revealed an association between
      TNF-alpha -308G/A gene polymorphism and risk of sepsis (AA+GA vs. GG, OR 1.35,
      95% CI 1.10-1.67, P = 0.005). This association was observed in the Caucasian
      subgroup (OR 1.50, 95% CI 1.13-2.00, P = 0.006), but not in the Asian subgroup.
      Across the entire study population, the polymorphism was also significantly
      related to septic shock risk (OR 1.52, 95% CI 1.18-1.95, P = 0.001) but not to
      sepsis-related mortality (OR 0.99, 95% CI 0.71-1.40, P = 0.97). Conclusions: This
      meta-analysis suggests that the -308G/A gene polymorphism in the TNF-alpha gene
      may contribute to risk of sepsis and septic shock, but not risk of mortality.

PMID- 29212278
TI  - Efficacy and safety of pancreatic enzyme replacement therapy on exocrine
      pancreatic insufficiency: a meta-analysis.
AB  - Background: Pancreatic enzyme replacement therapy (PERT) is widely applied to
      patients with exocrine pancreatic insufficiency (EPI), but its effect and safety
      has not been quantified. Therefore we performed a meta-analysis to determine the
      efficacy and tolerance of PERT on patients with EPI. Materials and Methods:
      PubMed, Medline, Cochrane library database, Evidence-based medicine/clinical
      trials published before December 2016 were searched by two independent reviewers
      to identify prospective randomized controlled trials (RCTs). Results: Seven RCTs,
      randomizing a total of 282 patients, were filtrated and assessed qualitatively
      (Jadad score). PERT increased CFA (WMD: 26.56, 20.35 to 32.76, I2= 79.6%, P <
      0.001) compared with baseline, and CFA (WMD: 17.97, 12.61 to 23.34, I2 = 76.7%, P
      < 0.001) vs. placebo. Meanwhile, CNA, SFE, SNE and SW were significantly improved
      in PERT compared with baseline and placebo, with no statistical differences in
      adverse events. Subgroup analysis indicated that standard forms of PERT displayed
      more effectiveness with significantly decreased heterogeneity, and large sample
      size also reduced the heterogeneity to some degree. Conclusions: PERT is
      demonstrated to be effective and tolerable in patients with EPI, especially using
      standard administration of PERT. Larger and higher quality studies on EPI are
      demanded to long-term effect of standard PERT treatment.

PMID- 29212279
TI  - Association between depression and brain tumor: a systematic review and meta
      analysis.
AB  - Background: Patients with brain tumor are in risk of depression or depressive
      symptoms, but the estimated prevalence varies between studies. The aim of this
      study is to get a proper summarized estimate of depression prevalence in brain
      tumor patients. Methods: Literature search on Pubmed, PsycINFO, and Cochrane
      library from January 1981 through October 2016. The prevalence of depression or
      depressive symptoms in brain tumor patients was estimated by screening scales and
      analyzed using stratified meta-analysis and subgroup analysis. The prevalence of
      depression level or symptoms during the follow-up periods was detected by
      secondary analysis. Results: Among the 37 studies included in this meta-analysis,
      25 used a cross-sectional design and 12 used longitudinal study. The pooled
      prevalence was 21.7% (971/4518 individuals, 95 % confidence interval (CI) 18.2%
      25.2%) for overall sample. Lower prevalence was detected in studies with sample
      size >=100 than <100, lower grade tumor than high grade tumor, studies using
      clinician-rated depression scales than self-rated or non-depression-specific
      ones, and in patients from UK, Germany and Italy than USA. After analyzing 6
      longitudinal studies, prevalence of depression remained no change in the follow
      up periods. No significant differences were observed between study designs and
      tumor types. Conclusions: The estimated prevalence of depression or depressive
      symptoms among brain tumor patients was 21.7%, affected by depression assessment
      type, sample size, tumor grade and country. Diagnosis and treatment of co-morbid
      depression in brain tumor patients need to be addressed in future studies for
      better life quality and oncology management.

PMID- 29212280
TI  - Influence of body mass index on postoperative complications after thymectomy in
      myasthenia gravis patients.
AB  - Objectives: It is not clear whether being overweight or obese influences
      postoperative complications in myasthenia gravis (MG) patients. We
      retrospectively investigated an association between body mass index (BMI) and
      postoperative complications in MG. Materials and Methods: Fifty-nine MG patients
      who had undergone transsternal thymectomy were classified as low or high BMI
      based on the criteria for Asian-Pacific populations. An association between BMI
      and complications was analyzed. Results: MG patients with high BMI had
      significantly higher rates of major adverse complications (P = 0.033),
      postoperative respiratory failure (P = 0.045), and longer postoperative
      hospitalization (P = 0.005). The optimal cutoff value of BMI for postoperative
      respiratory failure was 23.3 kg/m2, with a sensitivity of 75.0% and a specificity
      of 64.7% (P = 0.046). Conclusions: MG patients with a BMI indicating overweight
      or obesity have a higher risk of postoperative complications after thymectomy.
      Thus, close monitoring must be performed when surgery is necessary.

PMID- 29212281
TI  - Genetic predisposition toward suicidal ideation in patients with acute coronary
      syndrome.
AB  - The genetic predisposition toward suicidal ideation has been explored to identify
      subgroups at high risk and to prevent suicide. Acute coronary syndrome (ACS) is
      associated with an increased risk of suicide, but few studies have explored the
      genetic predisposition toward suicide in ACS populations. Therefore, this
      longitudinal study explored the genetic predisposition toward suicidal ideation
      in ACS patients. In total, of 969 patients within 2 weeks after ACS, 711 were
      followed at 1 year after ACS. Suicidal ideation was evaluated with the relevant
      items on the Montgomery-Asberg Depression Rating Scale. Ten genetic polymorphisms
      associated with serotonergic systems, neurotrophic factors, carbon metabolism,
      and inflammatory cytokines were examined. Associations between genetic
      polymorphisms and suicidal ideation within 2 weeks and 1 year of ACS were
      investigated using logistic regression models. The 5-HTTLPR s allele was
      significantly associated with suicidal ideation within 2 weeks of ACS after
      adjusting for covariates and after the Bonferroni correction. TNF-alpha -308G/A,
      IL-1beta -511C/T, and IL-1beta + 3953C/T were significantly associated with
      suicidal ideation within 2 weeks after ACS, but these associations did not reach
      significance after the Bonferroni correction in unadjusted analyses and after
      adjusting for covariance. However, no significant association between genetic
      polymorphisms and suicidal ideation was found at 1 year. Genetic predisposition,
      5-HTTLPR s allele in particular, may confer susceptibility to suicidal ideation
      in ACS patients during the acute phase of ACS.

PMID- 29212282
TI  - Intravoxel incoherent motion diffusion-weighted MR imaging of the liver using
      respiratory-cardiac double triggering.
AB  - To investigate the influence of respiratory-cardiac double triggering (RCT) on
      intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for the
      liver, twelve healthy volunteers underwent liver DWI twice respectively with
      respiratory triggering (RT) and RCT schemes. Signal-to-noise ratios (SNRs) of the
      images, values, repeatability (evaluating with within-subject coefficient of
      variation), and variability of quantitative parameters, including apparent
      diffusion coefficient (ADC), pure diffusion coefficient (D), perfusion fraction
      (f), and perfusion-related diffusion coefficient (D*), were evaluated for each
      DWI sequence. Results showed that the use of RCT scheme significantly enhanced
      SNRs (P < 0.001), improved the measurement precision (P <= 0.023) and
      repeatability (P <= 0.009) of ADC, D, and f values, decreased the variability of
      ADC and D values (P <= 0.015). Furthermore, this improvement was not completely
      confined to the left liver lobe, but also observed for the right liver lobe.
      Moreover, the precision of D* values in the right lobe (P < 0.001) and its
      repeatability in the left lobe (P = 0.002) were also significantly improved.
      Thus, our findings suggest that RCT is a more effective physiological scheme for
      improving SNRs, the precision, repeatability, and variability of quantitative
      parameters than RT for IVIM-DWI in the liver.

PMID- 29212283
TI  - 18F-Fluoromisonidazole in tumor hypoxia imaging.
AB  - Hypoxia is a common feature of solid tumors that is closely associated with
      radiotherapy and chemotherapy resistance, metastasis and tumors prognosis. Thus,
      it is important to assess hypoxia in tumors for estimating prognosis and
      selecting appropriate treatment procedures. 18F-Fluoromisonidazole positron
      emission tomography (18F-FMISO PET) has been widely used to visualize tumor
      hypoxia in a comprehensive and noninvasive way, both in the clinical and
      preclinical settings. Here we review the concept, mechanisms and detection
      methods of tumor hypoxia. Furthermore, we discuss the correlation between 18F
      FMISO PET and other detection methods, current applications of 18F-FMISO PET and
      the development prospects of this imaging technology.

PMID- 29212284
TI  - Systematic review and critique of circulating miRNAs as biomarkers of stage I-II
      non-small cell lung cancer.
AB  - Selected circulating microRNAs (miRNAs) have been suggested for non-invasive
      screening of non-small cell lung cancer (NSCLC), however the numerous proposed
      miRNA signatures are inconsistent. Aiming to identify miRNAs suitable
      specifically for stage I-II NSCLC screening in serum/plasma samples, we searched
      the databases "Pubmed", "Medline", "Scopus", "Embase" and "WOS" and
      systematically reviewed the publications reporting quantitative data on the
      efficacy [sensitivity, specificity and/or area under the curve (AUC)] of
      circulating miRNAs as biomarkers of NSCLC stage I and/or II. The 20 studies
      fulfilling the search criteria included 1110 NSCLC patients and 1009 controls,
      and were of medium quality according to Quality Assessment of Diagnostic Accuracy
      Studies checklist. In these studies, the patient cohorts as well as the control
      groups were heterogeneous for demographics and clinicopathological
      characteristics; moreover, numerous pre-analytical and analytical variables
      likely influenced miRNA determinations, and potential bias of hemolysis was often
      underestimated. We identified four circulating miRNAs scarcely influenced by
      hemolysis, each featuring high sensitivity (> 80%) and AUC (> 0.80) as biomarkers
      of stage I-II NSCLC: miR-223, miR-20a, miR-448 and miR-145; four other miRNAs
      showed high specificity (> 90%): miR-628-3p, miR-29c, miR-210 and miR-1244. In a
      model of two-step screening for stage I-II NSCLC using first the above panel of
      serum miRNAs with high sensitivity and high AUC, and subsequently the panel with
      high specificity, the estimated overall sensitivity is 91.6% and overall
      specificity is 93.4%. These and other circulating miRNAs suggested for stage I-II
      NSCLC screening require validation in multiple independent studies before they
      can be proposed for clinical application.

PMID- 29212285
TI  - BANCR: a novel oncogenic long non-coding RNA in human cancers.
AB  - Long non-coding RNAs account for large proportion of non-coding transcripts in
      human genomes. Though they lack of open reading framework and cannot encode
      protein, they can control endogenous gene expression though regulating cell life
      activities. They serve as transcriptional modulator, posttranscriptional
      processor, chromatin remodeler and splicing regulator during the process of gene
      modification. Moreover, long non-coding RNAs were regarded as potential tumor
      markers for cancer diagnosis and prognosis. BANCR was identified as a cancer
      promoting long non-coding RNA in melanoma tissues. Since then, increasing studies
      about BANCR in cancer progression were reported. BANCR was dysregulated in
      various cancers including melanoma, colorectal cancer, retinoblastoma, lung
      carcinoma and hepatocellular carcinoma, and increased BANCR expression cause poor
      prognosis and shorter survival rate of cancer patients. Furthermore, the
      functions and mechanisms of BANCR in cancer cells have been clarified. Here, we
      focus on the current research on the role of BANCR in the clinical management,
      progression and molecular mechanisms in human cancer.

PMID- 29212287
TI  - The benefit of everolimus in recurrent/epithelioid angiosarcoma patients: Case
      reports and literature review.
AB  - Epithelioid angiosarcoma (EA) is a kind of rare malignant soft tissue sarcoma,
      with high recurrence/metastatic rate and poor prognosis. To date, no effective
      standardized treatment regimen has been available for patients with
      recurrence/metastatic EA. Everolimus is an oral rapamycin derivative that highly
      inhibits the mechanistic target of rapamycin(mTOR) signal pathway. Previous
      studies have suggested that everolimus is effective and safe in some soft tissue
      sarcoma. We reported two cases with recurrence/metastatic EA, who received
      everolimus after failure of surgery, radiotherapy, chemotherapy or interventional
      therapy. Two cases obtained clinical benefit within 1 week, and were evaluated as
      partial response (PR). The progression free survival (PFS) time was nearly 12.0
      and 6.0 months, respectively. The overall survival (OS) time was 18.0 and 10.0
      months, respectively. The main adverse event was stomatitis syndrome (grade 1-2),
      which was well controllable and tolerable. It indicated that everolimus may be
      more beneficial for recurrence/metastatic EA patients.

PMID- 29212286
TI  - Regulation of DNA replication-coupled histone gene expression.
AB  - The expression of core histone genes is cell cycle regulated. Large amounts of
      histones are required to restore duplicated chromatin during S phase when DNA
      replication occurs. Over-expression and excess accumulation of histones outside S
      phase are toxic to cells and therefore cells need to restrict histone expression
      to S phase. Misregulation of histone gene expression leads to defects in cell
      cycle progression, genome stability, DNA damage response and transcriptional
      regulation. Here, we discussed the factors involved in histone gene regulation as
      well as the underlying mechanism. Understanding the histone regulation mechanism
      will shed lights on elucidating the side effects of certain cancer
      chemotherapeutic drugs and developing potential biomarkers for tumor cells.

PMID- 29212288
TI  - Failure of ocular photodynamic therapy for secondary choroidal metastasis: a case
      report and literature review.
AB  - The choroid is the most common site for intraocular metastatic disease.
      Photodynamic therapy (PDT) can effectively destroy malignant tissue and induce
      anti-tumor activity. Recent publications support its use as an effective therapy
      for the treatment of choroidal metastases, especially in the subfoveal region,
      resulting in subsequent vision preservation or improvement. Here, we introduce a
      case of choroidal metastasis, secondary to primary lung cancer. The progression
      of choroidal metastasis after PDT was followed up using spectral domain optical
      coherence tomography with point-to-point follow-up. Unfortunately, both the
      choroidal metastasis and serous retinal detachment increased after PDT. Since the
      mechanism underlying the therapeutic effect of PDT on choroidal metastasis is
      still not fully understood, deeper investigations into its safety, underlying
      molecular mechanisms, and treatment effects are critical for further PDT clinical
      usage in intraocular choroidal metastases.

PMID- 29212289
TI  - A Novel Thrombolytic and Anticoagulant Serine Protease from Polychaeta, Diopatra
      sugokai.
AB  - Ischemic stroke can result from blockage of blood vessels, forming fibrin clots
      in the body and causing irreparable brain damage. Remedial thrombolytic agents or
      anticoagulants have been studied; however, because the FDA-approved tissue
      plasminogen activator has low efficacy and side effects, it is necessary to
      develop safer and more effective treatment candidates. This study aimed at
      assessing the fibrinolytic and anticoagulation features of a novel serine
      protease extracted and purified from Diopatra sugokai, a polychaeta that inhabits
      tidal flats. The purified serine protease was obtained through ammonium sulfate
      precipitation, affinity chromatography, and ion-exchange chromatography. Its
      molecular size was identified via SDS-PAGE. To characterize its enzymatic
      activities, the protease activity at various pH and temperatures, and in the
      presence of various inhibitors, was measured via azocasein assay. Its
      fibrinolytic activity and anticoagulant effect were assessed by fibrin
      zymography, fibrin plate assay, and fibrinogenolytic activity assays. The novel
      38 kDa serine protease had strong indirect thrombolytic activity rather than
      direct activity over broad pH (4-10) and temperature (37 degrees C-70 degrees C)
      ranges. In addition, the novel serine protease exhibited anticoagulant activity
      by degrading the alpha-, beta-, and gamma-chains of fibrinogen. In addition, it
      did not produce cytotoxicity in endothelial cells. Therefore, this newly isolated
      serine protease is worthy of further investigation as a novel alkaline serine
      protease for thrombolytic therapy against brain ischemia.

PMID- 29212290
TI  - Isolation and Evaluation of Bacillus Strains for Industrial Production of 2,3
      Butanediol.
AB  - Biologically produced 2,3-butanediol (2,3-BDO) has diverse industrial
      applications. In this study, schematic isolation and screening procedures were
      designed to obtain generally regarded as safe (GRAS) and efficient 2,3-BDO
      producers. Over 4,000 candidate strains were isolated by pretreatment and
      enrichment, and the isolated Bacillus strains were further screened by
      morphological, biochemical, and genomic analyses. The screened strains were then
      used to test the utilization of the most common carbon (glucose, xylose,
      fructose, sucrose) and nitrogen (yeast extract, corn steep liquor) sources for
      the economical production of 2,3-BDO. Two-stage fed-batch fermentation was
      finally carried out to enhance 2,3-BDO production. In consequence, a newly
      isolated Bacillus licheniformis GSC3102 strain produced 92.0 g/l of total 2,3-BDO
      with an overall productivity and yield of 1.40 g/l/h and 0.423 g/g glucose,
      respectively, using a cheap and abundant nitrogen source. These results strongly
      suggest that B. licheniformis, which is found widely in nature, can be used as a
      host strain for the industrial fermentative production of 2,3-BDO.

PMID- 29212291
TI  - Fecal Respiratory Viruses in Acute Viral Respiratory Infection and Nasopharyngeal
      Diarrheal Viruses in Acute Viral Gastroenteritis: Clinical Impact of Ectopic
      Viruses Is Questionable.
AB  - Our aim was to determine the detection rate of respiratory viruses (RVs) in feces
      of patients with acute viral respiratory infection (AVRI) and the detection rate
      of diarrheal viruses (DVs) in nasopharyngeal samples from patients with acute
      viral gastroenteritis. The relationships between the presence of fecal RVs or
      nasopharyngeal DVs and their impacts on the clinical severity were also
      investigated. A total of 144 fecal specimens were collected from AVRI patients
      and 95 nasopharyngeal specimens were collected from acute viral gastroenteritis
      patients. Clinical characteristics and laboratory profiles were compared between
      subgroups on the basis of the presence or absence of virus in the specimens. The
      detection rate of RVs in feces was 17.4% (25/144), whereas the detection rate for
      viruses identical to the respiratory pathogen was 10.4% (identical group,
      15/144). Within the identical group, adenovirus (86.7%, 13/15) was most commonly
      found. Patients in the identical group showed statistically higher values for C
      reactive protein, mean age, increased frequency of vomiting, and decreased
      frequency of chest film involvement and cough (p < 0.05). The detection rate of
      nasopharyngeal DVs among acute viral gastroenteritis patients was 19.0% (18/95),
      and in the identical group it was 15.8% (15/95). Norovirus group II and enteric
      adenovirus were the major pathogens detected in the identical group. There were
      no significant differences in clinical characteristics and laboratory profiles
      between the subgroups. In conclusion, the major pathogens of fecal RV and
      nasopharyngeal DV were adenovirus and norovirus group II, respectively. However,
      their relationship with the clinical symptoms or disease severity is unclear.

PMID- 29212292
TI  - Construction of Luminescence- and Fluorescence-Tagged Burkholderia pseudomallei
      for Pathogen Tracking in a Mouse Model.
AB  - Molecular imaging is a powerful method for tracking various infectious disease
      causing pathogens in host organisms. Currently, a dual molecular imaging method
      that can provide temporal and spatial information on infected hosts at the
      organism, organ, tissue, and cellular levels simultaneously has not been reported
      for Burkholderia pseudomallei, a high-risk pathogen that causes melioidosis. In
      this study, we have established an experimental method that provides
      spatiotemporal information on infected hosts using luminescent and fluorescent
      dual-labeled B. pseudomallei. Using this method, we visualized B. pseudomallei
      infection at the organism, organ, and tissue levels in a BALB/c mouse model by
      detecting its luminescence and fluorescence. The infection of B. pseudomallei at
      the cellular level was also visualized by its emitted fluorescence in infected
      macrophage cells. This method could be an extremely useful and applicable tool to
      study the pathogenesis of B. pseudomallei-related infectious diseases.

PMID- 29212293
TI  - Enhancement of Ethanol Production via Hyper Thermal Acid Hydrolysis and Co
      Fermentation Using Waste Seaweed from Gwangalli Beach, Busan, Korea.
AB  - The waste seaweed from Gwangalli beach, Busan, Korea was utilized as biomass for
      ethanol production. Sagassum fulvellum (brown seaweed, Mojaban in Korean name)
      comprised 72% of the biomass. The optimal hyper thermal acid hydrolysis
      conditions were obtained as 8% slurry contents, 138 mM sulfuric acid, and 160
      degrees C of treatment temperature for 10 min with a low content of inhibitory
      compounds. To obtain more monosaccharides, enzymatic saccharification was carried
      out with Viscozyme L for 48 h. After pretreatment, 34 g/l of monosaccharides were
      obtained. Pichia stipitis and Pichia angophorae were selected as optimal co
      fermentation yeasts to convert all of the monosaccharides in the hydrolysate to
      ethanol. Co-fermentation was carried out with various inoculum ratios of P.
      stipitis and P. angophorae. The maximum ethanol concentration of 16.0 g/l was
      produced using P. stipitis and P. angophorae in a 3:1 inoculum ratio, with an
      ethanol yield of 0.47 in 72 h. Ethanol fermentation using yeast co-culture may
      offer an efficient disposal method for waste seaweed while enhancing the
      utilization of monosaccharides and production of ethanol.

PMID- 29212294
TI  - Purification, Characterization, and Cloning of a Cold-Adapted Protease from
      Antarctic Janthinobacterium lividum.
AB  - In this study, a 107 kDa protease from psychrophilic Janthinobacterium lividum
      PAMC 26541 was purified by anion-exchange chromatography. The specific activity
      of the purified protease was 264 U/mg, and the overall yield was 12.5%. The J.
      lividum PAMC 25641 protease showed optimal activity at pH 7.0-7.5 and 40 degrees
      C. Protease activity was inhibited by PMSF, but not by DTT. On the basis of the N
      terminal sequence of the purified protease, the gene encoding the cold-adapted
      protease from J. lividum PAMC 25641 was cloned into the pET-28a(+) vector and
      heterologously expressed in Escherichia coli BL21(DE3) as an intracellular
      soluble protein.

PMID- 29212295
TI  - Inhibitory Effects of Boesenbergia pandurata on Age-Related Periodontal
      Inflammation and Alveolar Bone Loss in Fischer 344 Rats.
AB  - Periodontitis, an infective disease caused by oral pathogens and the intrinsic
      aging process, results in the destruction of periodontal tissues and the loss of
      alveolar bone. This study investigated whether Boesenbergia pandurata extract
      (BPE) standardized with panduratin A exerted anti-periodontitis effects, using an
      aging model representative of naturally occurring periodontitis. In aged rats,
      the oral administration of BPE (200 mg.kg-1.day-1) for 8 weeks significantly
      reduced the mRNA and protein expression of interleukin-1beta, nuclear factor
      kappa B, matrix metalloproteinase (MMP)-2, and MMP-8 in gingival tissues (p <
      0.01). In alveolar bone, histological analysis with staining and micro-computed
      tomography revealed the attenuation of alveolar bone resorption in the BPE
      treated aged group, which led to a significant reduction in the mRNA and protein
      expression of nuclear factor of activated T-cells c1 (NFATc1), c-Fos, tartrate
      resistant acid phosphatase, and cathepsin K (p < 0.01). BPE not only increased
      the expression of osteoblast differentiation markers, such as alkaline phosphate,
      and collagen type I (COL1A1), but also increased the ratio of osteoprotegerin to
      RANKL. Collectively, the results strongly suggested that BPE is a natural
      resource for the prevention or treatment of periodontal diseases.

PMID- 29212296
TI  - Immune Enhancement Effect of Asterias amurensis Fatty Acids through NF-kappaB and
      MAPK Pathways on RAW 264.7 Cells.
AB  - Asterias amurensis is a marine organism that causes damage to the fishing
      industry worldwide; however, it has been considered a promising source of
      functional components. The present study aimed to investigate the immune
      enhancing effects of fatty acids from three organs of A. amurensis on murine
      macrophages (RAW 264.7 cells). A. amurensis fatty acids boosted production of
      immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW
      264.7 cells. A. amurensis fatty acids also enhanced the expression of critical
      immune-associated genes, including iNOS, TNF-alpha, IL-1beta, and IL-6, as well
      as COX-2. Western blotting showed that A. amurensis fatty acids stimulated the NF
      kappaB and MAPK pathways by phosphorylation of NF-kappaB p-65, p38, ERK1/2, and
      JNK. A. amurensis fatty acids from different tissues resulted in different levels
      of NF-kappaB and MAPK phosphorylation in RAW 264.7 cells. The results increase
      our understanding of how A. amurensis fatty acids boost immunity in a
      physiological system, as a potential functional material.

PMID- 29212297
TI  - Enhanced Production of Fatty Acids via Redirection of Carbon Flux in Marine
      Microalga Tetraselmis sp.
AB  - Lipids in microalgae are energy-rich compounds and considered as an attractive
      feedstock for biodiesel production. To redirect carbon flux from competing
      pathways to the fatty acid synthesis pathway of Tetraselmis sp., we used three
      types of chemical inhibitors that can block the starch synthesis pathway or
      photorespiration, under nitrogen-sufficient and nitrogen-deficient conditions.
      The starch synthesis pathway in chloroplasts and the cytosol can be inhibited by
      3-(3,4-dichlorophenyl)-1,1-dimethylurea and 1,2-cyclohexane diamine tetraacetic
      acid (CDTA), respectively. Degradation of glycine into ammonia during
      photorespiration was blocked by aminooxyacetate (AOA) to maintain biomass
      concentration. Inhibition of starch synthesis pathways in the cytosol by CDTA
      increased fatty acid productivity by 27% under nitrogen deficiency, whereas the
      blocking of photorespiration in mitochondria by AOA was increased by 35% under
      nitrogen-sufficient conditions. The results of this study indicate that blocking
      starch or photorespiration pathways may redirect the carbon flux to fatty acid
      synthesis.

PMID- 29212298
TI  - Bioconversion of Tetracycline Antibiotics to Novel Glucoside Derivatives by
      Single-Vessel Multienzymatic Glycosylation.
AB  - The single-vessel multienzyme UDP-alpha-D-glucose recycling system was coupled
      with a forward glucosylation reaction to produce novel glucose moiety-conjugated
      derivatives of different tetracycline antibiotic analogs. Among five tetracycline
      analogs used for the reaction, four molecules (chlorotetracycline,
      doxytetracycline, meclotetracycline, and minotetracycline) were accepted by a
      glycosyltransferase enzyme, YjiC, from Bacillus licheniformis to produce
      glucoside derivatives. However, the enzyme was unable to conjugate sugar units to
      rolitetracycline. All glucosides of tetracycline derivatives were characterized
      by ultraviolet absorbance maxima, ultra-pressure liquid chromatography coupled
      with photodiode array, and high-resolution quadruple time-of-flight electrospray
      mass spectrometry analyses. These synthesized glucosides are novel tetracycline
      derivatives.

PMID- 29212299
TI  - Modulating the Properties of Metal-Sensing Whole-Cell Bioreporters by Interfering
      with Escherichia coli Metal Homeostasis.
AB  - In Escherichia coli, the transcription of genes related to metal homeostasis is
      activated by the presence of target metals. The promoter regions of those genes
      can be fused with reporter genes to generate whole-cell bioreporters (WCBs);
      these organisms sense the presence of target metals through reporter gene
      expression. However, the limited number of available promoters for sensing
      domains restricts the number of WCB targets. In this study, we have demonstrated
      an alternative method to generate novel WCBs, based on the notion that since the
      sensing mechanisms of WCBs are related to metal transportation systems, their
      properties can be modulated by disrupting metal homeostasis. Mutant E. coli
      strains were generated by deleting the znt-operon genes zntA, which encodes a
      zinc-export protein, and zntR, which encodes a znt-operon regulatory protein, to
      investigate the effects on the metal-sensing properties of WCBs. Deletion of zntA
      increased the sensitivity but abolished the selectivity of cadmium-sensing WCBs,
      whereas arsenic-sensing WCBs gained sensitivity toward cadmium. When zntR was
      deleted, cadmium-sensing WCBs lost the ability to detect cadmium, and this was
      recovered by introducing exogenous zntR. In addition, the metal-binding site of
      ZntR was genetically engineered to modulate metal selectivity. This study
      provides a valuable platform for the development of novel E. coli-based WCBs.

PMID- 29212300
TI  - Cancer Metabolism: a Hope for Curing Cancer.

PMID- 29212301
TI  - Convergence of Cancer Metabolism and Immunity: an Overview.
AB  - Cancer metabolism as a field of research was founded almost 100 years ago by Otto
      Warburg, who described the propensity for cancers to convert glucose to lactate
      despite the presence of oxygen, which in yeast diminishes glycolytic metabolism
      known as the Pasteur effect. In the past 20 years, the resurgence of interest in
      cancer metabolism provided significant insights into processes involved in
      maintenance metabolism of non-proliferating cells and proliferative metabolism,
      which is regulated by proto-oncogenes and tumor suppressors in normal
      proliferating cells. In cancer cells, depending on the driving oncogenic event,
      metabolism is re-wired for nutrient import, redox homeostasis, protein quality
      control, and biosynthesis to support cell growth and division. In general,
      resting cells rely on oxidative metabolism, while proliferating cells rewire
      metabolism toward glycolysis, which favors many biosynthetic pathways for
      proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented
      to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms,
      however, are insufficient to drive tumorigenesis because immune surveillance
      continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion
      of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells,
      which are also attenuated by the metabolic tumor microenvironment, which is rich
      in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine,
      and the proton (low pH). As such, a full understanding of tumor metabolism
      requires an appreciation of the convergence of cancer cell intrinsic metabolism
      and that of the tumor microenvironment including stromal and immune cells.

PMID- 29212303
TI  - Targeting Glutamine Metabolism for Cancer Treatment.
AB  - Rapidly proliferating cancer cells require energy and cellular building blocks
      for their growth and ability to maintain redox balance. Many studies have focused
      on understanding how cancer cells adapt their nutrient metabolism to meet the
      high demand of anabolism required for proliferation and maintaining redox
      balance. Glutamine, the most abundant amino acid in plasma, is a well-known
      nutrient used by cancer cells to increase proliferation as well as survival under
      metabolic stress conditions. In this review, we provide an overview of the role
      of glutamine metabolism in cancer cell survival and growth and highlight the
      mechanisms by which glutamine metabolism affects cancer cell signaling.
      Furthermore, we summarize the potential therapeutic approaches of targeting
      glutamine metabolism for the treatment of numerous types of cancer.

PMID- 29212302
TI  - A New Perspective on the Heterogeneity of Cancer Glycolysis.
AB  - Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and
      nutrient needs to support cellular proliferation and physiological function. For
      many years, a central hallmark of tumor metabolism has emphasized a uniformly
      elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to
      extensive efforts of targeting glycolysis in human cancers. However, clinical
      attempts to target glycolysis and glucose metabolism have proven to be
      challenging. Recent advancements revealing a high degree of metabolic
      heterogeneity and plasticity embedded among various human cancers may paint a new
      picture of metabolic targeting for cancer therapies with a renewed interest in
      glucose metabolism. In this review, we will discuss diverse oncogenic and
      molecular alterations that drive distinct and heterogeneous glucose metabolism in
      cancers. We will also discuss a new perspective on how aberrantly altered
      glycolysis in response to oncogenic signaling is further influenced and remodeled
      by dynamic metabolic interaction with surrounding tumor-associated stromal cells.

PMID- 29212304
TI  - The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy.
AB  - During cancer progression, cancer cells are repeatedly exposed to metabolic
      stress conditions in a resource-limited environment which they must escape.
      Increasing evidence indicates the importance of nicotinamide adenine dinucleotide
      phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic
      stress conditions, such as metabolic resource limitation and therapeutic
      intervention. NADPH is essential for scavenging of reactive oxygen species (ROS)
      mainly derived from oxidative phosphorylation required for ATP generation. Thus,
      metabolic reprogramming of NADPH homeostasis is an important step in cancer
      progression as well as in combinational therapeutic approaches. In mammalian, the
      pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of
      NADPH production. In this review, we focus on the importance of glucose flux
      control towards PPP regulated by oncogenic pathways and the potential therein for
      metabolic targeting as a cancer therapy. We also summarize the role of Snail
      (Snai1), an important regulator of the epithelial mesenchymal transition (EMT),
      in controlling glucose flux towards PPP and thus potentiating cancer cell
      survival under oxidative and metabolic stress.

PMID- 29212305
TI  - Cancer Energy Metabolism: Shutting Power off Cancer Factory.
AB  - In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when
      13 mM glucose was added, which was identified as being due to lactate. When
      glucose is the only source of nutrient, it can serve for both biosynthesis and
      energy production. However, a series of studies revealed that the cancer cell
      consumes glucose for biosynthesis through fermentation, not for energy supply,
      under physiological conditions. Recently, a new observation was made that there
      is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually
      regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic
      metabolism and release lactate which is used by oxygenated cancer cells. This
      study challenged the Warburg effect, because Warburg claimed that fermentation by
      irreversible damaging of mitochondria is a fundamental cause of cancer. However,
      recent studies revealed that mitochondria in cancer cell show active function of
      oxidative phosphorylation although TCA cycle is stalled. It was also shown that
      blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined
      with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP
      production, which resulted in a significant regression of tumor growth in the
      NSCLC model. This suggests a new theory that NADH production in the cytosol plays
      a key role of ATP production through the mitochondrial electron transport chain
      in cancer cells, while NADH production is mostly occupied inside mitochondria in
      normal cells.

PMID- 29212306
TI  - Oncogene-Driven Metabolic Alterations in Cancer.
AB  - Cancer is the leading cause of human deaths worldwide. Understanding the biology
      underlying the evolution of cancer is important for reducing the economic and
      social burden of cancer. In addition to genetic aberrations, recent studies
      demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency,
      accumulation of intermediates of glycolysis, and upregulation of lipid and amino
      acid synthesis, in several types of cancer to support their high demands on
      nutrients for building blocks and energy production. Moreover, oncogenic
      mutations are known to be associated with metabolic reprogramming in cancer, and
      these overall changes collectively influence tumor-microenvironment interactions
      and cancer progression. Accordingly, several agents targeting metabolic
      alterations in cancer have been extensively evaluated in preclinical and clinical
      settings. Additionally, metabolic reprogramming is considered a novel target to
      control cancers harboring un-targetable oncogenic alterations such as KRAS.
      Focusing on lung cancer, here, we highlight recent findings regarding metabolic
      rewiring in cancer, its association with oncogenic alterations, and therapeutic
      strategies to control deregulated metabolism in cancer.

PMID- 29212307
TI  - Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic
      Opportunities.
AB  - Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox
      metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are
      maintained at very low levels because of their ubiquitination and proteasomal
      degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3
      ubiquitin ligase complex. However, oxidative and/or electrophilic stresses
      disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and
      transactivation of NRF2. During recent decades, a growing body of evidence
      suggests that NRF2 is frequently activated in many types of cancer by multiple
      mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This
      suggested that NRF2 inhibition is a promising strategy for cancer therapy.
      Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy.
      Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its
      contribution to the tumor development and radiochemoresistance. In addition,
      among the NRF2 inhibitors reported so far, we summarize and discuss repurposed
      NRF2 inhibitors with their potential mechanisms and provide new insights to
      develop selective NRF2 inhibitors.

PMID- 29212308
TI  - Metabolic Signaling to Epigenetic Alterations in Cancer.
AB  - Cancer cells reprogram cellular metabolism to support the malignant features of
      tumors, such as rapid growth and proliferation. The cancer promoting effects of
      metabolic reprogramming are found in many aspects: generating additional energy,
      providing more anabolic molecules for biosynthesis, and rebalancing cellular
      redox states in cancer cells. Metabolic pathways are considered the pipelines to
      supply metabolic cofactors of epigenetic modifiers. In this regard, cancer
      metabolism, whereby cellular metabolite levels are greatly altered compared to
      normal levels, is closely associated with cancer epigenetics, which is implicated
      in many stages of tumorigenesis. In this review, we provide an overview of cancer
      metabolism and its involvement in epigenetic modifications and suggest that the
      metabolic adaptation leading to epigenetic changes in cancer cells is an
      important non-genetic factor for tumor progression, which cooperates with genetic
      causes. Understanding the interaction of metabolic reprogramming with epigenetics
      in cancers may help to develop novel or highly improved therapeutic strategies
      that target cancer metabolism.

PMID- 29212309
TI  - Imaging Cancer Metabolism.
AB  - It is widely accepted that altered metabolism contributes to cancer growth and
      has been described as a hallmark of cancer. Our view and understanding of cancer
      metabolism has expanded at a rapid pace, however, there remains a need to study
      metabolic dependencies of human cancer in vivo. Recent studies have sought to
      utilize multi-modality imaging (MMI) techniques in order to build a more detailed
      and comprehensive understanding of cancer metabolism. MMI combines several in
      vivo techniques that can provide complementary information related to cancer
      metabolism. We describe several non-invasive imaging techniques that provide both
      anatomical and functional information related to tumor metabolism. These imaging
      modalities include: positron emission tomography (PET), computed tomography (CT),
      magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) that uses
      hyperpolarized probes and optical imaging utilizing bioluminescence and
      quantification of light emitted. We describe how these imaging modalities can be
      combined with mass spectrometry and quantitative immunochemistry to obtain more
      complete picture of cancer metabolism. In vivo studies of tumor metabolism are
      emerging in the field and represent an important component to our understanding
      of how metabolism shapes and defines cancer initiation, progression and response
      to treatment. In this review we describe in vivo based studies of cancer
      metabolism that have taken advantage of MMI in both pre-clinical and clinical
      studies. MMI promises to advance our understanding of cancer metabolism in both
      basic research and clinical settings with the ultimate goal of improving
      detection, diagnosis and treatment of cancer patients.

PMID- 29212310
TI  - Quality Metrics of a Fecal Immunochemical Test-Based Colorectal Cancer Screening
      Program in Korea.
AB  - Background/Aims: Knowledge regarding the quality metrics of fecal immunochemical
      test (FIT)-based colorectal cancer screening programs is limited. The aim of this
      study was to investigate the performance and quality metrics of a FIT-based
      screening program. Methods: In our screening program, asymptomatic subjects aged
      >=50 years underwent an annual FIT, and subjects with positive FIT results
      underwent a subsequent colonoscopy. The performance of the FIT and colonoscopy
      was analyzed in individuals with a positive FIT who completed the program between
      2009 and 2015 at a university hospital. Results: Among the 51,439 screened
      participants, 75.1% completed the FIT. The positive rate was 1.1%, and the
      colonoscopy completion rate in these patients was 68.6%. The positive predictive
      values of cancer and advanced neoplasia were 5.5% and 19.1%, respectively. The
      adenoma detection rate in the patients who underwent colonoscopy after a positive
      FIT was 48.2% (60.0% for men and 33.6% for women). The group with the highest
      tertile quantitative FIT level showed a significantly higher detection rate of
      advanced neoplasia than the group with the lowest tertile (odds ratio, 2.6; 95%
      confidence interval, 1.4 to 5.1; p<0.001). Conclusions: The quality metrics used
      in the United States and Europe may be directly introduced to other countries,
      including Korea. However, the optimal quality metrics should be established in
      each country.

PMID- 29212311
TI  - A Prospective Study on the Prevalence, Extent of Disease and Outcome of
      Eosinophilic Gastroenteritis in Patients Presenting with Lower Abdominal
      Symptoms.
AB  - Background/Aims: The epidemiology of eosinophilic gastroenteritis remains
      unclear. We aim to determine the prevalence of eosinophilic gastroenteritis in
      patients with lower abdominal symptoms. Methods: In a prospective study,
      colonoscopy was performed on 2,469 consecutive patients. Biopsies were taken from
      the terminal ileum and ascending, transverse, descending and sigmoid colon in all
      patients. Results: Sixty-four of the 2,469 patients (2.6%) had eosinophilic
      gastroenteritis. Only five of the 64 patients (7.8%) with eosinophilic
      gastroenteritis had endoscopic mucosal abnormalities during colonoscopy. Six of
      these 64 patients (9.4%) had severe disease at presentation, and seven of these
      64 patients (10.9%) required systemic steroid treatment. An elevated absolute
      peripheral eosinophil count was independently associated with severe disease at
      presentation (4/6 [66.7%] vs 3/58 [5.2%], p=0.005; odds ratio [OR], 25.320; 95%
      confidence interval [CI], 2.628 to 243.910), and severe disease at the time of
      presentation was independently associated with the use of systemic steroid
      treatment (6/7 [85.7%] vs 0/57 [0%], p=0.008; OR, 18.021; 95% CI, 2.163 to
      150.152). Conclusions: The prevalence of eosinophilic gastroenteritis is common,
      and patients usually present normal-appearing mucosa on colonoscopy. Those with
      severe disease at presentation usually have a raised absolute peripheral
      eosinophil count and should be commenced on systemic steroids as an initial
      therapy.

PMID- 29212312
TI  - Groove Pancreatitis: Endoscopic Treatment via the Minor Papilla and Duct of
      Santorini Morphology.
AB  - Background/Aims: Groove pancreatitis (GP) is an uncommon disease involving the
      pancreaticoduodenal area. Possible pathogenesis includes obstructive pancreatitis
      in the duct of Santorini and impaired communication with the duct of Wirsung,
      minor papilla stenosis, and leakage causing inflammation. Limited data regarding
      endoscopic treatment have been published. Methods: Seven patients with GP
      receiving endoscopic treatment were reviewed. The morphology of the pancreatic
      duct was evaluated by a pancreatogram. Endoscopic dilation of the minor papilla
      and drainage of the duct of Santorini were performed. Results: There were two
      pancreatic divisum cases, one ansa pancreatica case and four impaired connections
      between the duct of Santorini and the main pancreatic duct. Three to 31 sessions
      of endoscopy, with 2 to 24 sessions of transpapillary stenting and dilation, were
      performed. Interventions through the minor papilla were successfully performed in
      six of seven cases. The pancreatic stenting duration ranged from 2 to 87 months.
      Five patients with evidence of chronic pancreatitis (CP) tended to receive more
      endoscopic interventions than did the two patients without CP (2-24 vs 2,
      respectively) for GP and other complications associated with CP. Conclusions:
      Disconnection or impairment of communication between the ducts of Santorini and
      Wirsung was observed in all cases of GP. No surgery was required, and endoscopic
      minor papilla dilation and drainage of the duct of Santorini were feasible for
      the treatment of GP.

PMID- 29212313
TI  - Clinical Outcomes of Standard Triple Therapy Plus Probiotics or Concomitant
      Therapy for Helicobacter pylori Infection.
AB  - Background/Aims: The efficacy of standard triple therapy (STT) in treating
      Helicobacter pylori infection has decreased. Many investigators have attempted to
      increase the eradication rate. We investigated the outcomes of concomitant
      therapy (CT) and STT combined with probiotics (STP) as a first-line treatment for
      H. pylori infection. Methods: We reviewed the medical records of 361 patients who
      received either STP (n=286) or CT (n=75). The STP group received STT combined
      with a probiotic preparation for 1 week. The CT group received STT and
      metronidazole for 1 week. Results: The intention-to-treat and per-protocol
      eradication rates were 83.6% (95% confidence interval [CI], 79.0 to 87.7) and
      87.1% (95% CI, 81.2 to 89.7) in the STP group and 86.7% (95% CI, 78.7 to 93.3)
      and 91.4% (95% CI, 83.6 to 97.1) in the CT group (p=0.512 and p=0.324),
      respectively. The frequency of adverse effects was higher in the CT group (28.2%)
      than in the STP group (12.8%) (p=0.002). Conclusions: STP and CT are
      encouragingly efficacious as first-line treatments for H. pylori infection.
      Therefore, adding probiotics to STT may be a feasible option to avoid side
      effects.

PMID- 29212316
TI  - Titanium-Oxide Host Clusters with Exchangeable Guests.
AB  - A novel family of water-soluble, polyoxocationic titanium-oxide host-guest
      clusters are reported herein. They exhibit an unprecedented hexagonal prismatic
      core structure for hosting univalent cationic guests like K+, Rb+, Cs+ and H3O+.
      Guest exchange has been studied using 133Cs NMR, showing the flexible pore of a
      host permits passage of a comparatively larger cation and giving an equilibrium
      constant of ca. 13 for displacing Rb+ by Cs+. Attractive ion-dipole interaction,
      depending on host-guest size complementarity, plays a dominant role for the
      preferential encapsulation of larger alkali-metal cationic guests.

PMID- 29212314
TI  - Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir
      and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b.
AB  - Background/Aims: Changes in lipid profiles in patients infected with hepatitis C
      virus (HCV) during direct-acting antiviral therapy have been reported in recent
      years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV
      infection have not been fully elucidated. Methods: Dynamic changes in serum
      total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)
      cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b
      were examined during combination therapy with daclatasvir (DCV) and asunaprevir
      (ASV). Results: Total, LDL-, and HDL-cholesterol levels increased rapidly and
      persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C
      III levels were significantly higher at week 4 than at week 0. In contrast, apo A
      II and apo E levels were significantly lower. The differences in LDL- and HDL
      cholesterol levels were positively correlated with those of apo B and apo A-I,
      respectively. Interestingly, in patients with non-sustained virological response,
      these cholesterol levels decreased rapidly after viral breakthrough or viral
      relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C
      III levels. Conclusions: Clearance of HCV using combination therapy with DCV and
      ASV results in rapid changes in serum lipid profiles, suggesting an influence of
      HCV infection on disturbed lipid metabolism.

PMID- 29212315
TI  - Post-ERCP Bleeding in the Era of Multiple Antiplatelet Agents.
AB  - Background/Aims: This study aimed to determine the risk of post-endoscopic
      retrograde cholangiopancreatography (post-ERCP) bleeding among patients taking
      antiplatelet agents (APAs), particularly in the era of multiple APAs. Methods:
      The primary outcomes were the frequency, type, and severity of ERCP-related
      bleeding according to the use of APAs. Results: The frequencies of post-ERCP
      bleeding among the four different groups were 16 of 2,083 (0.8%) in the no drug
      group, 12 of 256 (4.7%) in the aspirin group, 3 of 48 (6.3%) in the single APA
      group, and 4 of 48 (8.3%) in the multiple APA group (p<0.001). In the univariate
      analysis, post-ERCP bleeding was associated with age, pull-type sphincterotomy,
      and APA and was inversely associated with balloon dilation of the biliary
      orifice. In the multivariate analysis, pull-type sphincterotomy (odds ratio [OR],
      7.829; 95% confidence interval [CI], 1.411 to 43.453; p=0.019) and country
      (Korea: OR, 0.124; 95% CI, 0.042 to 0.361; p<0.001) were associated with post
      ERCP bleeding. Conclusions: The frequency of post-ERCP bleeding was statistically
      higher in patients on any APA within 6 days prior to ERCP. However, in the
      multivariate analysis, APA use was not associated with post-ERCP bleeding. Until
      a large, adequately powered study to detect differences is performed, caution is
      recommended when considering invasive procedures during ERCP in patients on APAs.

PMID- 29212318
TI  - Protein Binding Kinetics in Multimodal Systems: Implications for Protein
      Separations.
AB  - In this work, quartz crystal microbalance with dissipation (QCM-D) was employed
      to study the kinetic processes involved in the interaction of proteins with self
      assembled monolayers (SAMs) of multimodal (MM) ligands. SAMs were fabricated to
      mimic two chromatographic multimodal resins with varying accessibility of the
      aromatic moiety to provide a well-defined model system. Kinetic parameters were
      determined for two different proteins in the presence of the arginine and
      guanidine and a comparison was made with chromatographic retention data. The
      results indicated that the accessibility of the ligand's aromatic moiety can have
      an important impact on the kinetics and chromatographic retention behavior.
      Interestingly, arginine and guanidine had very different effects on the protein
      adsorption and desorption kinetics in these MM systems. For cytochrome C,
      arginine resulted in a significant decrease and increase in the adsorption and
      desorption rates, respectively, while guanidine produced a dramatic increase in
      the desorption rate, with minimal effect on the adsorption rate. In addition, at
      different concentrations of arginine, two distinct kinetic scenarios were
      observed. For alpha-chymotrypsin, the presence of 0.1 M guanidine in the aromatic
      exposed ligand system produced an increase in the adsorption rate and only a
      moderate increase in the desorption rate, which helped to explain the surprising
      increase in the chromatographic salt elution concentration. These results
      demonstrate that protein adsorption kinetics in the presence of different mobile
      phase modifiers and MM ligand chemistries can play an important role in
      contributing to selectivity in MM chromatography.

PMID- 29212319
TI  - Discriminating Live and Dead Cells in Dual-Color Mode with a Two-Photon
      Fluorescent Probe Based on ESIPT Mechanism.
AB  - Discrimination of live and dead cells is an important task in biological,
      pathological, medical, and pharmaceutical studies. In this work, we have
      developed a novel fluorescent probe DACA that can discriminate live and dead
      cells in a dual-color mode for the first time. DACA can stain dead cells with
      blue fluorescence peaked at 440 nm, while it can also label live cells with
      orange emission peaked at 570 nm. Compared with one-color fluorescent probes,
      such a dual-color probe can efficiently avoid false positive results from
      cellular autofluorescence and misleading signals brought by inhomogeneous
      staining, and thus can supply more accurate information in biological
      applications. By means of DACA, the health status of tumor cells pretreated by
      H2O2 and ultraviolet radiation has been successfully detected and imaged.
      Moreover, DACA and the hydrolyzed product exhibit excellent two-photon
      properties. Live and dead cells, as well as the zebrafishes, have been
      discriminated with dual emission colors under one- and two-photon microscope.
      These results demonstrate that DACA is a powerful tool for dual-color
      distinguishing live and dead cells in vitro and in vivo.

PMID- 29212317
TI  - Targeted Measurements of O- and N-Glycopeptides Show That Proteins in High
      Density Lipoprotein Particles Are Enriched with Specific Glycosylation Compared
      to Plasma.
AB  - High density lipoprotein (HDL) particles are believed to be protective due to
      their inverse correlation with the prevalence of cardiovascular diseases.
      However, recent studies show that in some conditions such as heart disease and
      diabetes, HDL particles can become dysfunctional. Great attention has been
      directed toward HDL particle composition because the relative abundances of HDL
      constituents determine HDL's functional properties. A key factor to consider when
      studying the structure and composition of plasma particles is the protein
      glycosylation. Here, we profile the O- and N-linked glycosylation of HDL
      associated-proteins including the truncated form of Apo CIII and their glycan
      heterogeneity in a site-specific manner. Apolipoprotein CIII, fetuin A, and alpha
      1 antitrypsin are glycoproteins associated with lipoproteins and are implicated
      in many cardiovascular and other disease conditions. A targeted method (UHPLC
      QQQ) was used to measure the glycoprotein concentrations and site-specific
      glycovariations of the proteins in human plasma and compared with HDL particles
      isolated from the same plasma samples. The proteins found in the plasma are
      differentially glycosylated compared to those isolated in HDL. The results of
      this study suggest that glycosylation may play a role in protein partitioning in
      the blood, with possible functional implications.

PMID- 29212320
TI  - Effect of Ammonia and Formic Acid on the OH* + HCl Reaction in the Troposphere:
      Competition between Single and Double Hydrogen Atom Transfer Pathways.
AB  - Quantum chemical calculations at QCISD and CCSD(T) levels of theory have been
      performed to investigate the effect of NH3 and HCO2H on the reaction between OH*
      and HCl. Potential energy profiles indicate that both NH3 and HCO2H catalyzed
      reactions could proceed through two different channels, namely, single and double
      hydrogen atom transfer. Theoretically calculated rate constants for both the
      catalysts show that both NH3 and HCO2H catalyzed channels prefer a single
      hydrogen atom transfer path. Besides, both NH3 and HCO2H catalyzed paths have
      higher rate constant values as compared to that of the water catalyzed path.

PMID- 29212321
TI  - On the Thermodynamic Stability of Clathrate Hydrates VI: Complete Phase Diagram.
AB  - We develop a method to evaluate the thermodynamic stability of clathrate hydrates
      relative to host water and/or guest species. This enables to investigate complete
      phase behaviors of clathrate hydrates in the whole space of the thermodynamic
      variables, not only temperature and pressure but also composition, with only the
      intermolecular interactions as input parameters. A complete phase diagram of
      clathrate hydrate is settled with this method, specifically the region enclosed
      by the hydrate/water and hydrate/guest phase boundaries where a clathrate hydrate
      is the only stable phase. The method is applied to methane clathrate hydrate,
      which results in an excellent agreement in dissociation pressure with the
      experimental observations. It is found that the hydrate/water phase boundary is
      significantly affected by the phase transition of water from ice to liquid. This
      transition limits the stable area of the clathrate hydrate terminated at the
      dissociation temperature, which otherwise exhibits unphysical divergence. It is
      essential to choose a pressure as an independent variable so as to calculate the
      accurate phase equilibria in composition space. The present method establishes a
      pressure-temperature-composition relation for a single stable phase of clathrate
      hydrate as well as recovering its temperature dependence of the dissociation
      pressure.

PMID- 29212322
TI  - An Electrochemical Reaction-Diffusion Model of the Photocatalytic Effect of
      Photosystem I Multilayer Films.
AB  - The photosynthetic protein, photosystem I (PSI), has been used as a photoactive
      species within a host of biohybrid photoelectrochemical systems. PSI multilayer
      films at electrode surfaces provide greatly improved solar energy conversion
      relative to homologous monolayer films. While the photocatalytic effect of PSI
      multilayers has been theorized as an electrolyte-mediated mechanism, no
      comprehensive, first-principles modeling study has been presented. In this work,
      we develop and optimize an electrochemical reaction-diffusion model to replicate
      the significant electrochemical, physicochemical, and transport processes that
      underpin photocurrent development of a PSI multilayer film. We use this model to
      provide strong evidence that PSI's terminal cofactors rapidly exchange electrons
      with diffusible mediators and stimulate photocurrent principally due to
      alteration of mediator concentrations at a solution-electrode interface as
      governed by Butler-Volmer kinetics. Our fitted model accurately replicates
      photocurrent trends under a variety of conditions, including variable applied
      bias and PSI multilayer film thickness.

PMID- 29212323
TI  - Asymmetric Synthesis of Dihydrocoumarins through Chiral Phosphoric Acid-Catalyzed
      Cycloannulation of para-Quinone Methides and Azlactones.
AB  - A chiral phosphoric acid-catalyzed approach constructing dihydrocoumarin motifs
      by the addition of azlactones to para-quinone methides (p-QMs) was developed. The
      reaction proceeded smoothly with a wide range of p-QMs and azlactones to generate
      corresponding products in high yields with excellent diastereoselectivities
      (>19:1 dr) and enantioselectivities (up to 99% ee). Two possible pathways were
      proposed to explain the stereoselectivity.

PMID- 29212324
TI  - Preparation of Ultrasensitive Humidity-Sensing Films by Aerosol Deposition.
AB  - Aerosol deposition (AD) is a novel ceramic film preparation technique exhibiting
      the advantages of room-temperature operation and highly efficient film growth.
      Despite these advantages, AD has not been used for preparing humidity-sensing
      films. Herein, room-temperature AD was utilized to deposit BaTiO3 films on a
      glass substrate with a Pt interdigital capacitor, and their humidity-sensing
      performances were evaluated in detail, with further optimization performed by
      postannealing at temperatures of 100, 200, ..., 600  degrees C. Sensor responses
      (i.e., capacitance variations) were measured in a humidity chamber for relative
      humidities (RHs) of 20-90%, with the best sensitivity (461.02) and a balanced
      performance at both low and high RHs observed for the chip annealed at 500 
      degrees C. In addition, its response and recovery were extremely fast,
      respectively, at 3 and 6 s and it kept a stable recording with the maximum error
      rate of 0.1% over a 120 h aging test. Compared with other BaTiO3-based humidity
      sensors, the above chip required less thermal energy for its preparation but
      featured a more than 2-fold higher sensitivity and a superior detection balance
      at RHs of 20-90%. Cross-sectional transmission electron microscopy imaging
      revealed that the prepared film featured a transitional variable-density
      structure, with moisture absorption and desorption being promoted by a specific
      capillary structure. Finally, a bilayer physical model was developed to explain
      the mechanism of enhanced humidity sensitivity by the prepared BaTiO3 film.

PMID- 29212325
TI  - Chronic Heat Stress Impairs the Quality of Breast-Muscle Meat in Broilers by
      Affecting Redox Status and Energy-Substance Metabolism.
AB  - We investigated the molecular mechanisms by which chronic heat stress impairs the
      breast-meat quality of broilers. Broilers were assigned to three groups: the
      normal control (NC) group, heat-stress (HS) group, and pair-fed (PF) group. After
      7 days of heat exposure (32  degrees C), the high temperature had caused
      oxidative stress; elevated the activity of citrate synthase (CS), the mRNA
      expression of M-CPT1, and the phosphorylation level of AMPKalpha; and reduced the
      mRNA expression of avUCP. After 14 days of heat exposure, the heat stress had
      increased the lightness and drip loss and decreased the pH and shear force of the
      breast meat. Additionally, the heat exposure had increased the mRNA expressions
      of FAS, ACC, and PDK4; the content of lipids; and the activities of lactic
      dehydrogenase and pyruvate kinase, and it had decreased the mRNA expression of M
      CPT1 and the activity of CS. In conclusion, chronic heat stress impairs meat
      quality by causing mitochondria to malfunction and affecting energy-substance
      aerobic metabolism, resulting in increased glycolysis and intramuscular fat
      deposition.

PMID- 29212326
TI  - Folding Simulations of a Nuclear Receptor Box-Containing Peptide Demonstrate the
      Structural Persistence of the LxxLL Motif Even in the Absence of Its Cognate
      Receptor.
AB  - Regulation of nuclear receptors by their coactivators involves the recognition
      and binding of a specific sequence motif contained in the coactivator sequence.
      This motif is known as the nuclear receptor (NR) box and contains a conserved
      LxxLL subsequence, where L is leucine and x is any amino acid residue.
      Crystallographic studies have shown that the LxxLL motifs adopt an alpha-helical
      conformation when bound to their cognate nuclear receptors. Here we use an
      extensive set of folding molecular dynamics simulations to examine whether the
      alpha-helical conformation demonstrated by the LxxLL motifs in the bound state
      may represent a persistent structural preference of these peptides even in the
      absence of their cognate receptors. To this end, we have performed a grand total
      of 35 MUs of adaptive tempering folding simulations of an NR-box-containing
      peptide derived from Drosophila's fushi tarazu segmentation gene product. Our
      simulations-performed using full electrostatics and an explicit representation of
      two different solvents (water and a TFE/water mixture)-clearly indicate the
      presence of a persistent helical preference of the LxxLL motif with a concomitant
      native-like structure and contacts between the motif's leucine residues. To lend
      further support to our findings, we compare the simulation-derived peptide
      dynamics with experimental NMR-derived nuclear Overhauser effect (NOE)
      measurements that had been previously obtained for the same peptide in the same
      two solvents. The comparison demonstrates a quantitative agreement between
      simulation and experiment with average upper bound NOE violations of less than
      0.084 A, thus independently validating our main conclusion concerning the
      intrinsic preference of NR-box motifs to form helical structures even in the
      absence of their cognate receptors.

PMID- 29212327
TI  - Physical Insights from New Nanomaterials in Biology.

PMID- 29212328
TI  - Spotlights: Volume 8, Issue 23.

PMID- 29212329
TI  - Free-standing hydrogel-particle composite membrane with dynamically controlled
      permeability.
AB  - The preparation and investigation of a free-standing membrane made from a
      composite of thermoresponsive poly(N-isopropylacrylamide) (pNIPAAm) and
      polystyrene nanoparticles (PS NP) with temperature-controlled permeability is
      reported. The method exploits the light-induced crosslinking of the photo
      reactive pNIPAAm-based polymer and mechanical reinforcement of the membrane
      structure by the polystyrene nanoparticles. About micrometer thick layers were
      either directly attached to a gold surface or prepared as free-standing layers
      spanning over arrays of microfluidic channels with a width of about hundred
      microns by using template stripping. Diffusion of liquid medium, low molecular
      weight molecules, and large molecular weight proteins contained in blood through
      the composite membrane was observed with combined surface plasmon resonance (SPR)
      and optical waveguide spectroscopy (OWS). The swelling ratio, permeability, and
      nonspecific sorption to these composite membranes were investigated by SPR and
      OWS as a function of molecular weight of analyte, loading of PS NP in the
      composite film, and temperature. The authors show successful preparation of a
      defect-free membrane structure that acts as a thermoresponsive filter with
      nanoscale pores spanning over an area of several square millimeters. This
      membrane can be reversibly switched to block or allow the diffusion of low mass
      molecules to the sensor surface by temperature-triggered swelling and collapsing
      of the hydrogel component. Blocking of diffusion and low unspecific sorption of
      proteins contained in blood serum is observed. These features make this platform
      interesting for potential future applications in continuous monitoring biosensors
      for the analysis of low molecular weight drug analytes or for advanced cell-on
      chip microfluidic studies.

PMID- 29212330
TI  - Gastric mucus and mucuslike hydrogels: Thin film lubricating properties at soft
      interfaces.
AB  - Mucus is a viscous slime that plays a vital role in protecting and lubricating
      biological tissues, in particular, soft epithelium interfaces such as in the
      stomach, intestines, and esophagus. Previous attempts to generate mucus models
      that mimick or simulate its characteristics have been predominantly focused on
      the rheological properties. This study investigates both rheological and
      tribological shear properties of thin films of gastric mucus from a porcine
      source and its mimics at compliant soft interfaces. The lubricating efficacy of
      biological mucus and its mimics was observed to be superior at hydrophilic
      tribological interfaces compared to hydrophobic ones. Facile spreading of all
      mucus samples at hydrophilic steel-polydimethylsiloxane (PDMS) interfaces allowed
      for the retainment of the lubricating films over a wide range of speed,
      slide/roll ratio, and external load. In contrast, poor wetting at hydrophobic
      PDMS-PDMS interfaces led to depletion of the mucus samples from the interface
      with increasing speed. Among the different mucus models investigated in this
      study, fluid mixtures of commercially available porcine gastric mucin (PGM) and
      polyacrylic acid (PAA) displayed the most persistent lubricating effects under
      various tribological experimental conditions. A mixture of PGM and PAA holds a
      high potential as mucus mimic, not only for its rheological similarity, but also
      for its excellent lubricity in soft compliant and hydrophilic contacts.

PMID- 29212331
TI  - Enhanced antibacterial activity of silver-ruthenium coated hollow microparticles.
AB  - The oxidation based antimicrobial activity of silver is long known.
      Microparticles with a particular silver-ruthenium coating and specific physical
      properties were developed. The coating showed a considerably increased silver ion
      release rate in comparison to a plain silver coating. Accordingly, an exposure of
      Escherichia coli and Staphylococcus aureus to these silver-ruthenium coated
      microparticles resulted in a time and concentration dependent cell killing. Even
      though contact killing may contribute to this efficacy, rather a release
      associated diffusion gradient dependent killing was observed. Moreover, cell
      killing did not involve lysis. The coated microparticles manifested no reduction
      in antibacterial activity for months. Due to their specific size and density,
      they sedimented slowly in aqueous solution, showed a low aggregation tendency,
      and could be recycled easily. Hence, these silver-ruthenium coated microparticles
      lend themselves to a wide range of antibacterial applications as they combine
      long-term stability and high efficacy with ease of use.

PMID- 29212332
TI  - Quo vadis diabetes technology?
AB  - Management of patients with diabetes mellitus who require intensive insulin
      therapy has changed dramatically. From urine and then whole blood glucose
      monitoring patients can now wear personal continuous glucose monitors; from using
      multiple insulin injections they can now deliver subcutaneous insulin
      continuously using ever-more sophisticated insulin pumps. With the current
      integration of continuous glucose monitoring and insulin pumps a new era is
      arriving when "smart" insulin pumps can automate insulin delivery to assure more
      stable glycemic control while minimizing episodes of hypoglycemia. This review
      briefly summarizes results of key research studies demonstrating feasibility of
      the technology. It also discusses patient selection and potential challenges
      faced by attempting to incorporate diabetes technology into daily clinical
      practice. Finally, an overview of integrated systems in current and planned
      clinical trials is presented.

PMID- 29212333
TI  - [Quo vadis diabetes technology?]
AB  - Management of patients with diabetes mellitus who require intensive insulin
      therapy has changed dramatically. From urine and then whole blood glucose
      monitoring patients can now wear personal continuous glucose monitors; from using
      multiple insulin injections they can now deliver subcutaneous insulin
      continuously using ever-more sophisticated insulin pumps. With the current
      integration of continuous glucose monitoring and insulin pumps a new era is
      arriving when "smart" insulin pumps can automate insulin delivery to assure more
      stable glycemic control while minimizing episodes of hypoglycemia. This review
      briefly summarizes results of key research studies demonstrating feasibility of
      the technology. It also discusses patient selection and potential challenges
      faced by attempting to incorporate diabetes technology into daily clinical
      practice. Finally, an overview of integrated systems in current and planned
      clinical trials is presented.

PMID- 29212334
TI  - [Hyperlipoprotienemias and (not only) atherosclerosis: fragments from history and
      present].
AB  - The examples from the history, as well as the recent view, clearly demonstrate a
      great change in the perception of hyperlipoprotienemias and dyslipidemias (HLP
      and DLP) at the end of 20th and at the beginning of 21st century. Our aim is not
      a complex overview about HLP and DLP. We just want to describe the changing
      position and importance of these diseases in clinical medicine. We will touch
      cardiology, angiology, but also diabetology, hepatology and gastroenterology
      (pancreas). HLP and DLP, which started as a research topic in laboratory became
      clinically interesting as risk factors of atherosclerosis. They are understood as
      epidemic occurrence diseases, also in connection with metabolic syndrome.
      However, some of them, e.g. familial chylomicronemia or homozygous familial
      hypercholesterolemia fulfill criteria of rare diseases.

PMID- 29212335
TI  - [Glycemic variability and microvascular complications of diabetes].
AB  - Vascular complications of diabetes result from long lasting unsatisfactory
      glycemic control. We usually assess glycemic control based on the value of
      glycated hemoglobin HbA1c. The glycated hemoglobin test, however, says nothing
      about short-term glycemic fluctuations. Recently, continuous monitoring of
      glycemia has enabled us an in-depth assessment of changes in glucose
      concentrations, called glycemic variability. Together with the research of short
      term glycemic variability, also the study of long-term fluctuations in glycemic
      control based on HbA1c variability has now intensified. Glycemic variability may
      be related to oxidation stress, endothelial dysfunction and inflammation, the
      factors traditionally associated with vascular damage. This overview summarizes
      the recent findings in the field of glycemic variability and its possible
      association with microvascular complications in patients with type 1 and type 2
      diabetes.Key words: glycemic variability, HbA1c variability, microvascular
      complications, type 1 and type 2 diabetes mellitus.

PMID- 29212336
TI  - [New directions in bariatric and metabolic surgery].
AB  - Czech Republic may be counted among the leading European Countries in regards of
      the level of delivered high quality multidisciplinary care in treatment of
      obesity and obesity related metabolic diseases. The 1st Faculty of Medicine
      (Charles University) and the Faculty General Hospital in Prague played the most
      important role in the development of bariatric and metabolic surgery in the Czech
      Republic. pCzech bariatric surgery achieves great successes both on national and
      international levels. Just to mention some of them: M. Fried and M. Peskova were
      among the very first worldwide to implant the non-adjustable gastric banding
      laparoscopically in 1993, the Czech Republic was among the seven Countries to
      establish the International Federation for the Surgery of Obesity /IFSO/ (Fried
      in 1995), to organize the first IFSO World Congress in Prague (1996), to co
      establish the IFSO-European Chapter in Prague (2004), to implant the first SAGB
      VC worldwide (Fried, Dolezalova, 2007), to organize the first European Workshop
      on Gastric Plication (Fried, Dolezalova, 2010), to co-lead development of the
      European Interdisciplinary Guidelines on Metabolic and Bariatric Surgery (Fried
      et al.,2013), and many others. In the beginning of bariatric surgery, the almost
      only indication criterion for operation was the criterion of weight loss. On the
      turn of the Century metabolic surgery gradually gained importance. The most
      important indication criterion for metabolic operations started to be improvement
      and/or resolution of obesity related co-morbidities, such as type 2 diabetes
      mellitus. Thus, the criterion of successful treatment shifted from weight loss
      towards improvement and resolution of metabolic diseases regardless the body mass
      index. In conjunction with importance of metabolic surgery, more emphasis is
      given to lowering the invasiveness of so far available minimally
      invasive/laparoscopic approaches form the perioperative perspective as well as
      from the anatomically sparing/reversible surgeries.

PMID- 29212337
TI  - [Status of pharmacotherapy in current care of obese].
AB  - Weight loss drugs or anti-obesity drugs have a long history but are still far
      from being successful. Only in two last decades have the drugs been launched,
      which, when appropriately indicated, may be significantly beneficial to patients
      in need of weight loss as they are comparably effective to intensive programs to
      promote changes in eating habits and lifestyles. The combination
      naltrexone/bupropion is promising for food intake control including the reward
      mechanism, but the experience with its use has only been short-term. The lipase
      inhibitor orlistat remains the safest therapeutic option. The already restricted
      use of phentermine, newly classified as a controlled opiate substance, has become
      practically blocked. The range of weight loss drugs can be extended with some
      antidiabetics, particularly liraglutide and gliflozins. A number of other
      substances is still in the research stage.

PMID- 29212338
TI  - [Incidence of diabetes from the perspective of social security benefits].
AB  - The article analyzes the development of the activity of Medical Assessment
      Service for people with diabetes mellitus for selected assessment categories in
      the assessment of health conditions from 2012 to 2016. The assessment criteria
      for assessing disability, the degree of dependency for care allowance and the
      health status for grant for special aid, and certificate of person with
      disability are set out in the legislation. The incidence of disability for
      diabetes declined by 13 % between 2012 and 2016 and by 10 % for the degree of
      dependency for care allowance. The assessment for grant for special aid increased
      by 57 %, for grant in the case when the aid is a "vehicle" decreased by 8 %. Most
      importantly increased assessing for certificate of person with disability by 150
      %. The epidemic of diabetes in the population is not reflected in the incidence
      of disability and the degree of dependence. Both of these assessment categories
      were decreased, in spite of the fact that there account for almost 70 % of the
      whole assessment activity. The assessment for grant for special aid, and
      certificate of person with disability was increased. The cause may be due to
      incorrect statistical reporting, not up to date expert medical criteria, or poor
      patient awareness.

PMID- 29212339
TI  - [Anti-smoking act and the health care providers].
AB  - On May 31, 2017 the anti-smoking act came into effect. This act deals with a lot
      of rights and duties of the health care providers. These legal provisions are
      presented and summarized in this article.

PMID- 29212340
TI  - Encouragers and discouragers affecting medical graduates' choice of regional and
      rural practice locations.
AB  - INTRODUCTION: Access to health care as near to where people live as possible is
      desirable. However, not enough medical graduates choose to work in rural and
      regional areas, especially in general practice. The career decisions of recent
      medical graduates are known to be affected by a variety of professional, societal
      and personal factors. Internationally, medical programmes have exposed students
      to regional and rural experiences partly to encourage them to seek employment in
      these areas after graduation. As such, the Pukawakawa Programme is a year-long
      regional and rural experience for selected Year 5 students from the University of
      Auckland&lsquo;s Medical Programme in New Zealand in partnership with the
      Northland District Health Board and two Primary Health Organisations. A lack of
      clarity about the drivers of rural and regional career decisions underpinned this
      study, which aimed to explore the barriers and encouragers for students of the
      programme to return as resident medical officers to the regional hospital where
      they had gained clinical experience. METHODS: A mixed-method, descriptive design
      was used, including a short survey, followed by participation in a focus-group
      discussion or a one-on-one interview. Survey data were summarised in tabular form
      and inductive, thematic analysis was applied to transcripts of focus groups and
      interviews. RESULTS: Nineteen doctors in their first or second year following
      graduation participated: 15 who had returned to the hospital where they had
      clinical experience in the programme and four who were employed elsewhere. 'A
      match of personal goals and intended career intentions' was the reason most
      frequently selected for junior doctors&rsquo; choice of early career employment.
      Other frequently selected reasons were lifestyle, friends and family close by,
      and the reputation and experience of the Pukawakawa Programme. Qualitative data
      revealed that the learning experience, the unique design of the curriculum and
      associated support from clinicians were identified as important factors in
      encouraging students to work in regional and rural environments. However,
      discouraging factors included separation from friends and families, geographical
      isolation and the lack of opportunities for partners to find work. CONCLUSIONS:
      This study has confirmed the value of the Pukawakawa Programme as an important
      contributor to the regional and rural workforce of the Northland District, New
      Zealand. The value of an academic-clinical partnership has been shown to support
      a regional and rural clinical learning environment. Evidence is provided of one
      way of having overcome barriers to building regional and rural workforce capacity
      in this district.

PMID- 29212342
TI  - Reducing Unnecessary Testing: Ultrasound in Acute Kidney Injury.

PMID- 29212341
TI  - Scavenging Reactive Oxygen Species Production Normalizes Ferroportin Expression
      and Ameliorates Cellular and Systemic Iron Disbalances in Hemolytic Mouse Model.
AB  - AIMS: Release of large amounts of free heme into circulation, overproduction of
      reactive oxygen species (ROS), and activation of toll-like receptor-4-dependent
      responses are considered critical for the ability of heme to promote oxidative
      stress and to initiate proinflammatory responses, posing a serious threat to the
      body. A deep understanding of the consequences of heme overload on the regulation
      of cellular and systemic iron homeostasis is, however, still lacking. RESULTS:
      The effects of heme on iron metabolism were studied in primary macrophages and in
      mouse models of acute and chronic hemolysis. We demonstrated that hemolysis was
      associated with a significant depletion of intracellular iron levels and
      increased expression of the sole iron exporter protein, ferroportin. The
      pathophysiological relevance of this mechanism was further demonstrated in sickle
      cell anemia mice, which, despite chronic hemolysis, maintained high ferroportin
      expression and increased iron export. We identified a redox active iron species
      and superoxide as regulators for ferroportin induction by heme. Scavenging the
      ROS production, by use of a pharmacological antioxidant N-acetylcysteine,
      prevented ferroportin induction and normalized intracellular iron levels in
      macrophages and in experimentally induced hemolysis in mice. INNOVATION: Our data
      propose that scavenging ROS levels may be a novel therapeutic strategy to balance
      intracellular iron levels and systemic iron influx in conditions associated with
      heme overload. CONCLUSION: This study identifies that the pro-oxidant, and not
      the proinflammatory, actions of heme profoundly impact on iron homeostasis by
      critically regulating the expression of ferroportin and iron export in hemolytic
      conditions. Antioxid. Redox Signal. 29, 484-499.

PMID- 29212343
TI  - Nonbacterial thrombotic endocarditis involving all four cardiac valves.
AB  - This report describes a case of nonbacterial thrombotic endocarditis caused by
      Waldenstrom macroglobulinemia, with diffuse endocardial lesions and involvement
      of all 4 cardiac valves. A 77-year-old man presented with heart failure due to
      severe regurgitation of all 4 cardiac valves; surgical repair using bioprosthetic
      valves was indicated. A pathological study revealed fibrin-triggered thrombus
      formation that confirmed the diagnosis of nonbacterial thrombotic endocarditis.
      In cases of nonbacterial thrombotic endocarditis, the underlying cause should be
      investigated.

PMID- 29212344
TI  - Results Obtained by Combining Different Estimators of EEG Connectivity Become
      Uninterpretable If the Underlying Models Are Incompatible.
AB  - We comment on a recent article published in Brain Connectivity (Hatz et al., 2016
      ) that combined electroencephalography (EEG) microstate analysis with the phase
      locking index (PLI) and found that the test-retest reliability of connectivity
      patterns as obtained by the PLI increased when the data had been previously
      parcellated into microstates. Although we acknowledge the need to parcellate the
      continuous data into periods that supposedly correspond to transiently stable
      patterns of connectivity, we believe that the approach chosen by the authors is
      seriously mistaken. In particular, their approach disregards the particular a
      priori assumptions contained in each of the two methods that define connectivity
      in specific terms. Unfortunately, for microstate analyses and the PLI, these
      definitions are mutually exclusive, which makes attempts to draw any coherent
      conclusion in terms of comprehensibly interlinked biological processes
      meaningless. The occurrence of this type of problems should draw the attention to
      the importance of the particular methodological and conceptual features and
      limitations that come with the specific a priori assumptions contained in any
      quantifier of brain functional connectivity.

PMID- 29212345
TI  - A pilot investigation of an iOS-based app for toilet training children with
      autism spectrum disorder.
AB  - We developed an iOS-based app with a transmitter/disposable sensor and
      corresponding manualized intervention for children with autism spectrum disorder.
      The app signaled the onset of urination, time-stamped accidents for analysis,
      reminded parents to reinforce intervals of continence, provided a visual outlet
      for parents to communicate reinforcement, and afforded opportunity for timely
      feedback from clinicians. We compared this intervention with an intervention that
      uses standard behavioral treatment in a pilot randomized controlled trial of 33
      children with autism spectrum disorder aged 3-6 years with urinary incontinence.
      Parents in both groups received initial training and four booster consultations
      over 3 months. Results support the feasibility of parent-mediated toilet training
      studies (e.g., 84% retention rate, 92% fidelity of parent-implemented
      intervention). Parents used the app and related technology with few difficulties
      or malfunctions. There were no statistically significant group differences for
      rate of urine accidents, toilet usage, or satisfaction at close of intervention
      or 3-month follow-up; however, the alarm group trended toward greater rate of
      skill acquisition with significantly less day-to-day intervention. Further
      development of alarm and related technology and future comparative studies with a
      greater number of participants are warranted.

PMID- 29212346
TI  - Palliative Care Providers' Practices Surrounding Psychological Distress Screening
      and Treatment: A National Survey.
AB  - OBJECTIVE: To investigate how inpatient palliative care teams nationwide
      currently screen for and treat psychological distress. METHODS: A web-based
      survey was sent to inpatient palliative care providers of all disciplines
      nationwide asking about their practice patterns regarding psychological
      assessment and treatment. Descriptive statistics were used to characterize the
      sample and responses, and analysis of variance was conducted to determine whether
      certain disciplines were more likely to utilize specific treatment modalities.
      RESULTS: A total of N = 236 respondents were included in the final analyses.
      Providers reported that they encounter psychological distress regularly in their
      practice and that they screen for distress using multiple methods. When
      psychological distress is detected, providers reported referring patients to an
      average of 3 different providers (standard deviation = 1.46), most frequently a
      social worker (69.6%) or chaplain (65.3%) on the palliative care team. A total of
      84.6% of physicians and 54.5% of nurse practitioners reported that they prescribe
      anxiolytics or selective serotonin reuptake inhibitors to patients experiencing
      psychological distress. DISCUSSION AND CONCLUSIONS: This study revealed
      significant variability and redundancy in how palliative care teams currently
      manage psychological distress. The lack of consistency potentially stems from the
      variability in the composition of palliative care teams across care settings and
      the lack of scientific evidence for best practices in psychological care in
      palliative care. Future research is needed to establish best practices in the
      screening and treatment of psychological distress for patients receiving
      palliative care.

PMID- 29212347
TI  - Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water
      Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting Redox
      Imbalance.
AB  - SIGNIFICANCE: Modern technologies have eased our lives but these conveniences can
      impact our lifestyles in destructive ways. Noise pollution, mental stresses, and
      smoking (as a stress-relieving solution) are some environmental hazards that
      affect our well-being and healthcare budgets. Scrutinizing their pathophysiology
      could lead to solutions to reduce their harmful effects. Recent Advances:
      Oxidative stress plays an important role in initiating local and systemic
      inflammation after noise pollution, mental stress, and smoking. Lipid
      peroxidation and release of lysolipid by-products, disturbance in activation and
      function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of
      stress hormones and their secondary effects on intracellular kinases, and
      dysregulation of intracellular Ca2+ can all potentially trigger other vicious
      cycles. Recent clinical data suggest that boosting the antioxidant system through
      nonpharmacological measures, for example, lifestyle changes that include exercise
      have benefits that cannot easily be achieved with pharmacological interventions
      alone. CRITICAL ISSUES: Indiscriminate manipulation of the cellular redox network
      could lead to a new series of ailments. An ideal approach requires meticulous
      scrutiny of redox balance mechanisms for individual pathologies so as to create
      new treatment strategies that target key pathways while minimizing side effects.
      FUTURE DIRECTIONS: Extrapolating our understanding of redox balance to other
      debilitating conditions such as diabetes and the metabolic syndrome could
      potentially lead to devising a unifying therapeutic strategy. Antioxid. Redox
      Signal. 28, 741-759.

PMID- 29212348
TI  - Evaluating eight-year trajectories for sense of purpose in the health and
      retirement study.
AB  - OBJECTIVES: Though cross-sectional research has suggested that sense of purpose
      declines into older adulthood, it remains unclear whether inter-individual
      variability occurs in these trajectories, and what factors predict these
      trajectories. The current study provides one of the first longitudinal
      investigations into how individuals' sense of purpose fluctuates in older
      adulthood. METHOD: Participants from the Health and Retirement Study (n = 4,234,
      mean age = 65 years), completed assessments of sense of purpose over three years,
      along with multiple potential predictors (health, personality, demographics) at
      the start. RESULTS: Second-order latent growth models demonstrated both mean
      level declines on purpose over time, as well as the capacity for inter-individual
      variability in change patterns for retired adults. Among this cohort, health
      status, educational attainment, and marital status were significant predictors of
      purpose trajectories over time, though broad personality trait dimensions failed
      to uniquely predict change in sense of purpose. However, measurement invariance
      tests suggest that the scale did not operate similarly across work status groups.
      CONCLUSION: Findings advance the previous literature by demonstrating inter
      individual variability in sense of purpose for those participants who had
      retired. Future research should consider that purpose inventories may operate
      differently for those in the workplace versus retired adults.

PMID- 29212349
TI  - Comparison of In-Person and Online Motivational Interviewing-Based Health
      Coaching.
AB  - Health coaching is a common approach for promoting lifestyle changes, but little
      is known about the effectiveness of different delivery methods. The purpose of
      this study was to evaluate the effectiveness of in-person versus online health
      coaching when used as part of a facilitated behavior change program. To increase
      translatability, the study used a naturalistic design that enabled participants
      to self-select the coaching delivery method (Group) as well as the target
      behavior (diet, physical activity, or weight management). Regardless of group,
      participants were provided with a behavior-based monitoring device and guided to
      use it by the health coach. A sample of 92 adults participated and 86 completed
      pre-post evaluations to assess behavior change strategies and posttest outcome
      measurements for their specific goal. Two-way (Group * Time) analyses of variance
      were used to evaluate changes in behavioral strategies. Intent-to-treat
      regression analyses were used to compare postintervention outcomes for groups.
      The in-person group had significantly higher Healthy Eating Index scores than the
      online group ( p < .05), but nonsignificant group differences were observed for
      those targeting physical activity or weight change ( p > .05). The results
      support the use of health coaching for promoting behavior change and suggest that
      online coaching may be equally effective as in-person methods.

PMID- 29212350
TI  - The Effects of Cognitive Training on Cognitive Abilities and Everyday Function: A
      10-Week Randomized Controlled Trial.
AB  - With a random groups design, the current study examined whether a 10-week
      cognitive training could improve healthy older adult's cognitive functions and
      everyday problem-solving and whether high ecological validity trainings would
      have greater positive impact upon everyday problem-solving than low ecological
      validity trainings. Eighty-six healthy Chinese older adult participants were
      assigned randomly to five groups, including one control group receiving no
      training and four groups receiving low ecological memory training, high
      ecological memory training, low ecological reasoning training, and high
      ecological reasoning training, respectively. Participants were measured pre- and
      posttraining on spatial working memory, numerical working memory, reasoning, and
      everyday problem-solving. Results of this study showed that cognitive training
      significantly improved targeted cognitive functions and everyday problem-solving
      performance in all the intervention groups. However, high ecological cognitive
      trainings failed to show superior impact upon everyday problem-solving compared
      with low ecological cognitive trainings.

PMID- 29212352
TI  - Sounds Good-A Sonographic Approach for Dealing With a Rising Vascular Problem.

PMID- 29212353
TI  - Psoriasis and Cardiovascular Risk: Correlation Between Psoriasis and
      Cardiovascular Functional Indices.
AB  - Evidence suggests that psoriasis together with other cardiovascular (CV) risk
      factors is associated with increased vascular morbidity, but it is not clear
      whether psoriasis is an independent risk factor. Consecutive patients (n = 33;
      35.6 +/- 5.7 years; 13 females) with mild psoriasis (Psoriasis Area and Severity
      Index <10) without comorbidities and 33 healthy participants (36.3 +/- 5.9 years;
      15 females) were enrolled. Both groups underwent echocardiography, speckle
      tracking (2-dimensional strain echocardiography [2D-SE]), and pulse wave velocity
      (PWV) testing. Clinical and conventional echocardiographic characteristics were
      comparable between both groups. Global longitudinal strain (GLS) was
      significantly lower ( P = .002) in the psoriasis group (22.39% +/- 2.28%) than in
      controls (24.15% +/- 2.17%). The PWV was significantly lower ( P = .004) in
      controls (8.06 +/- 1.68 m/s) than in the psoriasis group (9.23 +/- 1.53 m/s).
      Significant correlations between GLS and disease duration ( r = -.66, P < .0001)
      and between GLS and patient age at diagnosis ( r = .48, P = .0043) were found.
      Psoriasis may be an independent CV risk factor, causing cardiac and vascular
      impairment. Both 2D-SE and PWV may be useful tools for the screening of CV risk
      in these patients.

PMID- 29212354
TI  - Image quality assessment of silent T2 PROPELLER sequence for brain imaging in
      infants.
AB  - OBJECTIVE: Infants are vulnerable to high acoustic noise. Acoustic noise
      generated by MR scanning can be reduced by a silent sequence. The purpose of this
      study is to compare the image quality of the conventional and silent T2 PROPELLER
      sequences for brain imaging in infants. METHODS: A total of 36 scans were
      acquired from 24 infants using a 3 T MR scanner. Each patient underwent both
      conventional and silent T2 PROPELLER sequences. Acoustic noise level was
      measured. Quantitative and qualitative assessments were performed with the images
      taken with each sequence. RESULTS: The sound pressure level of the conventional
      T2 PROPELLER imaging sequence was 92.1 dB and that of the silent T2 PROPELLER
      imaging sequence was 73.3 dB (reduction of 20%). On quantitative assessment, the
      two sequences (conventional vs silent T2 PROPELLER) did not show significant
      difference in relative contrast (0.069 vs 0.068, p value = 0.536) and signal-to
      noise ratio (75.4 vs 114.8, p value = 0.098). Qualitative assessment of overall
      image quality (p value = 0.572), grey-white differentiation (p value = 0.986),
      shunt-related artefact (p value > 0.999), motion artefact (p value = 0.801) and
      myelination degree in different brain regions (p values >= 0.092) did not show
      significant difference between the two sequences. CONCLUSION: The silent T2
      PROPELLER sequence reduces acoustic noise and generated comparable image quality
      to that of the conventional sequence. Advances in knowledge: This is the first
      report to compare silent T2 PROPELLER images with that of conventional T2
      PROPELLER images in children.

PMID- 29212355
TI  - The utility of contrast-enhanced hypodense sign for the diagnosis of pulmonary
      invasive mould disease in patients with haematological malignancies.
AB  - OBJECTIVE: The hypodense sign (HyS) on CT imaging is highly suggestive of
      pulmonary invasive mould disease (IMD) in patients with haematological
      malignancies, but its diagnostic utility has not been systematically evaluated on
      contrast-enhanced CT. The objective of this study was to compare the diagnostic
      performance of the HyS to other common CT findings in a cohort of haematology
      patients with proven, probable or possible IMD based on European Organization for
      Research and Treatment of Cancer/Mycoses Study Group criteria. METHODS: We
      analysed the diagnostic performance of the HyS to other common CT signs among 127
      neutropenic patients with haematological malignancies submitted to both non
      contrast-enhanced and contrast-enhanced CT scans of the lungs, including CT
      pulmonary angiography. RESULTS: The HyS was detected in 15.7% of patients imaged
      without contrast, and 44.1% after contrast administration. A contrast-aided HyS
      was detected in 86.6, 78.0 and 15.5% of patients with European Organization for
      Research and Treatment of Cancer/Mycoses Study Group proven, probable and
      possible IMD, respectively. When analysed per clinical diagnosis (proven,
      probable and highly possible IMD-i.e. no alternative diagnosis to mould disease
      reached), the contrast-enhanced HyS was as sensitive as the halo sign but
      significantly more specific [halo sign 0.56, 95% CI (0.39-0.71) vs HyS 0.98, 95%
      CI (0.87-1.00)]. Only the vessel occlusion sign was more sensitive [0.97, 95% CI
      (0.91-0.99)] and specific [0.97, 95% CI (0.86-0.99)] than the HyS for IMD
      diagnosis. CONCLUSION: The high specificity of the HyS strongly supports the
      diagnosis of pulmonary IMD in neutropenic patients, and is highly suggestive
      breakthrough fungal disease in patients on mould-active antifungal prophylaxis.
      Advances in knowledge: This is the first systematic analysis of the hypodense
      sign on contrast-enhanced CT; the sign can support the diagnosis of IMD when
      other CT signs are uncertain.

PMID- 29212351
TI  - The Multifaceted Impact of Peroxiredoxins on Aging and Disease.
AB  - SIGNIFICANCE: Peroxiredoxins (Prxs), a family of thiol-associated peroxidases,
      are purported to play a major role in sensing and managing hydrogen peroxide
      concentrations and transducing peroxide-derived signals. Recent Advances: Prxs
      can act as detoxifying factors and impart effects to cells that can be either
      sparing or suicidal. Advances have been made to address the qualitative changes
      in Prx function in response to quantitative changes in the signal level and to
      understand how Prx activity could be affected by their own substrates. Here we
      rationalize the basis for both positive and negative effects on signaling
      pathways and cell physiology, summarizing data from model organisms, including
      invertebrates. CRITICAL ISSUES: Resolving the relationship between the
      promiscuous behavior of reactive oxygen species and the specificity of Prxs
      toward different targets in redox-sensitive signaling pathways is a key area of
      research. Attempts to understand Prx function and underlying mechanisms were
      conducted in vitro or in vivo under nonphysiological conditions, leaving the
      physiological relevance yet to be defined. Other issues: Why despite the high
      degree of homology and similarities in subcellular and tissue distribution
      between Prxs do they display differential effects on signaling? How is the
      specificity of post-translational protein modifications determined? Other than
      chaperone-like activity, how do hyperoxidized Prxs function? FUTURE DIRECTIONS:
      Genetic models with mutated catalytic and resolving cysteines should be further
      exploited to dissect the functional significance of individual Prxs in their
      different states together with their alternative reducing partners. Such an
      analysis may then be extended to help identify Prx-specific targets.

PMID- 29212356
TI  - Does the total dysphagia risk score correlate with swallowing function examined
      by videofluoroscopy?
AB  - OBJECTIVE: The purpose of this study was to correlate the total dysphagia risk
      score (TDRS) with swallowing function as measured by videofluoroscopy of
      swallowing using the swallowing performance scale (SPS) and the penetration
      aspiration scale (PAS). METHODS: 63 patients from two different centres treated
      with radiotherapy for head and neck cancer were evaluated in the current study.
      Swallowing videofluoroscopies at baseline, 6 and 12 months following radiotherapy
      were evaluated by two observers. The TDRS of all patients was calculated and
      correlated with the consensus PAS and SPS scores of the two observers. RESULTS:
      Regarding the PAS scale, we did not observe a significant correlation with the
      TDRS. Regarding SPS, we found a significant correlation at 6 months (p = 0.01)
      and a borderline significant correlation at 12 months (p = 0.05). We observed
      statistically lower SPS scores for patients in the intermediate-risk category
      when compared to the high-risk category. When we compared low vs high TDRS risk
      patients, we did not observe a significant difference regarding SPS scores. When
      comparing low- vs intermediate-risk patients, we observed higher SPS scores in
      the low-risk group (p = 0.01). When the low- and intermediate-risk patients were
      grouped together, we observed less swallowing problems as measured by SPS in the
      low and intermediate group when compared to the high-risk group (p = 0.05) at 6
      months. CONCLUSION: Patients with high-risk TDRS scores have higher SPS scores
      when compared to the intermediate group and the intermediate- and low-risk group
      together. However, low-risk patients in our patient cohort could not be
      distinguished from high or intermediate-risk patients. Advances in knowledge:
      TDRS was never correlated with videofluoroscopies in past studies. The hypothesis
      of this paper was to see if the TDRS could guide us to see which patients are at
      risk for high scores on SPS and PAS and might need a videofluoroscopic
      examination in the follow up. Given the poor correlations in our study, however,
      we cannot recommend the use of the TDRS to select patients who might benefit from
      the additional information provided by videofluoroscopies.

PMID- 29212357
TI  - Manufacture of Third-Generation Lentivirus for Preclinical Use, with Process
      Development Considerations for Translation to Good Manufacturing Practice.
AB  - Lentiviral vectors are used in laboratories around the world for in vivo and ex
      vivo delivery of gene therapies, and increasingly clinical investigation as well
      as preclinical applications. The third-generation lentiviral vector system has
      many advantages, including high packaging capacity, stable gene expression in
      both dividing and post-mitotic cells, and low immunogenicity in the recipient
      organism. Yet, the manufacture of these vectors is challenging, especially at
      high titers required for direct use in vivo, and further challenges are presented
      by the process of translating preclinical gene therapies toward manufacture of
      products for clinical investigation. The goals of this paper are to report the
      protocol for manufacturing high-titer third-generation lentivirus for preclinical
      testing and to provide detailed information on considerations for translating
      preclinical viral vector manufacture toward scaled-up platforms and processes in
      order to make gene therapies under Good Manufacturing Practice that are suitable
      for clinical trials.

PMID- 29212358
TI  - A Mediation Analysis of Mothers' Dietary Intake: The Entre Familia: Reflejos de
      Salud Randomized Controlled Trial.
AB  - AIMS: Examine intervention effects among mothers involved in a healthy eating
      randomized controlled trial. Furthermore, examine the mediating roles of
      individual and familial influences on observed outcomes. METHODS: Between 2009
      and 2011, 361 families were recruited; half were assigned to an 11-session
      community health worker-delivered family-based intervention targeting Spanish
      speaking Latino families in Imperial County, California. The intervention was
      delivered over a 4-month period. Home visits and telephone calls were delivered
      approximately weekly, with tapering near the end of the intervention to promote
      independence from the promotora. In this article, mothers' self-reported dietary
      intake was the primary outcome. Evaluation measures were taken at baseline, 4
      months, and 10 months. RESULTS: Daily servings of fruits were higher among
      intervention versus control mothers (mean = 1.86 vs. mean = 1.47; effect size
      [ES] = 0.22) at 10 months post-baseline. Mothers in the intervention versus
      control condition also reported consuming a lower percent energy from fat (mean =
      30.0% vs. 31.0%; ES = 0.30) and a higher diet quality (mean = 2.93 vs. mean =
      2.67; ES = 0.29). Mediators of improvements were behavioral strategies to
      increase fiber and lower fat intake, family support for vegetable purchasing, and
      decreased unhealthy eating behaviors and perceived family barriers to healthy
      eating. DISCUSSION AND CONCLUSION: Family-based behavioral interventions are
      effective for changing the skills and family system needed to improve diet among
      Latina mothers. Health care providers and other practitioners are encouraged to
      target skill development and fostering a socially supportive environment.

PMID- 29212359
TI  - Anti-inflammatory constituents from Psychotria prainii H. Lev.
AB  - One new and three known compounds were isolated from the ethanol extract of
      Psychotria prainii aerial parts. By means of spectroscopic methods, their
      structures were elucidated to be deacetylasperulosidic acid 6-ethyl ether (1),
      asperulosidic acid (2), asperuloside (3) and obtucarbamates C (4). The isolated
      compounds were evaluated for their inhibitory effect on NO production in LPS
      stimulated RAW264.7 cells. Among them, compounds 2 and 4 exhibited strong effect
      with the IC50 values of 5.75 +/- 0.85 and 6.92 +/- 0.43 MUM, respectively. This
      is the first report for the chemical composition and biological activity of P.
      prainii.

PMID- 29212360
TI  - A new denudatine type C20-diterpenoid alkaloid from Aconitum sinchiangense W. T.
      Wang.
AB  - A new denudatine-type C20-diterpenoid alkaloid, designated as sinchianine (1),
      together with eight known diterpenoid alkaloids, 12-acetyl-12-epi-napelline (2),
      12-epi-napelline (3), neoline (4), talatisamine (5), 14-O-acetylsenbusine A (6)
      and benzoylaconine (7), songorine (8) and aconitine (9), were isolated from the
      whole herb of Aconitum sinchiangense W. T. Wang. Their structures were elucidated
      on the basis of extensive spectroscopic analyses (NMR and HR-ESI-MS) and
      comparison with data reported in the literature.

PMID- 29212361
TI  - Psychosocial Burden and Stigma Perception of Jordanian Patients With Epilepsy.
AB  - Epilepsy requires long-term treatment that interferes with individuals' social
      relationships. Because the effects of psychosocial burden and stigma perception
      on patients with epilepsy in Jordan have not been explored, the study assessed
      the relationship among psychosocial burden, stigma of epilepsy, and demographic
      variables. Subjects were adult patients with epilepsy ( N = 200) registered at
      hospital clinics. Two published instruments were used to measure outcomes. The
      participants in the study perceived the burden and stigma of epilepsy as
      moderate. A strong, positive correlation between psychosocial burden and stigma
      perception among participants was found. Stigma perception, employment, and
      education variables explained 31.6% of variation of the level of psychosocial
      burden. The results showed a relationship between stigma perception and
      psychosocial level, and this provides information that may assist health care
      providers in formulating strategic plans to improve the care, safety, and quality
      of life of patients with epilepsy in Jordan.

PMID- 29212362
TI  - How health professionals facilitate parents' involvement in decision-making at
      the hospital: A parental perspective.
AB  - In many western countries, parents have a legal right to influence and be
      involved in decision-making (DM) surrounding their children's healthcare. This
      ensures that the healthcare is customized as far as possible to meet the
      children's and families' needs and preferences. However, parental involvement in
      such DM is not sufficiently implemented and the parental role during
      hospitalizations has become demanding. More knowledge is required to inform
      health professionals (HPs) about how to improve parental involvement in DM from a
      health-promoting perspective. The aims of this study were to explore parents'
      experiences of how HPs facilitate their involvement in the DM surrounding their
      child's healthcare and to identify how HPs can improve parental involvement at
      the hospital. This was an explorative, descriptive qualitative study within a
      constructivist research paradigm, comprising a purposive sample of 12 parents
      participating in individual semi-structured interviews. Qualitative content
      analysis was performed. The findings showed that HPs' sensitivity to parents'
      capacity, resources and needs was essential in order to facilitate the latter's
      involvement in DM. HPs' sensitivity also seemed to influence the quality of
      communication and the HP-parent relationship. Moreover, these factors appeared to
      affect parents' coping ability during their children's hospitalization.

PMID- 29212363
TI  - Laparoscopic vs Percutaneous Cryotherapy for Renal Tumors: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Cryoablation has emerged as an alternative to the more invasive
      partial nephrectomy for small renal masses. The approach can be carried out by
      two techniques, either laparoscopic cryoablation (LCA) or percutaneous
      cryoablation, (PCA) with CT guidance. We aimed to compare between the two
      procedures. MATERIALS AND METHODS: A systematic review and meta-analysis was
      conducted, including studies comparing the two techniques. Outcomes included
      incomplete ablation, late local recurrence, cancer-specific survival, procedure
      time, transfusion rates, hospital stay, and complications. RESULTS: A total of
      1475 patients were included, 788 patients in the laparoscopic group and 687
      patients in the percutaneous group. There was statistical difference favoring the
      laparoscopic group with regard to having less incomplete ablation (p = 0.0008)
      and higher cancer-specific survival patients (p = 0.04). However, there was
      longer hospital stays in the LCA group (p < 0.00001) and was found to be more
      costly than the PCA group. There was significantly more Clavien-I complications
      in the PCA group (p = 0.001) and more Clavien-III complications in the LCA group
      (p = 0.001). Otherwise, there were no differences in any other outcome parameter.
      CONCLUSION: LCA was found to have less incomplete tumor ablation rates and higher
      cancer-specific survival rates, however, higher hospitalization time, more major
      complications (Clavien III), and was costlier compared with PCA.

PMID- 29212364
TI  - Corrigendum.

PMID- 29212365
TI  - Impact of metabolic control on macular thickness in diabetic macular oedema.
AB  - PURPOSE: To investigate the impact of metabolic control on macular thickness
      measured using optical coherence tomography in patients with diabetic retinopathy
      with or without macular oedema. METHODS: A total of 124 patients with diabetic
      retinopathy ( n = 70 without macular oedema and n = 54 with macular oedema) were
      enrolled. Optical coherence tomography parameters measured included central
      macular thickness and total macular volume. Metabolic factors with correlation to
      optical coherence tomography parameters were fasting plasma glucose, glycosylated
      haemoglobin, triglyceride, low-density lipoprotein and estimated glomerular
      filtration rate. Multiple linear regression models were used to evaluate
      associations between optical coherence tomography parameters and metabolic
      factors. RESULTS: Higher glycosylated haemoglobin values were correlated with
      increased central macular thickness in patients without macular oedema ( R =
      0.289, p = 0.015), whereas glycosylated haemoglobin values were inversely
      associated with central macular thickness in patients with macular oedema ( R = 
      0.374, p = 0.005). Both were found to be statistically significant after
      adjusting for age, sex and diabetic retinopathy severity in addition to other
      metabolic factors ( p = 0.009 and p = 0.002, respectively). CONCLUSION: Strict
      metabolic control may not be associated with better macular thickness in diabetic
      patients with co-existing macular oedema.

PMID- 29212366
TI  - A new12-membered lactone from the stems of Ficus auriculata.
AB  - A new lactone ficusine D (1), together with six known compounds (2-7) were
      isolated from the stems of the Ficus auriculata. The new compound 1 was a rare 12
      membered lactone containing a quinone ring skeleton. The structure of the 1 was
      elucidated by comprehensive spectroscopic data. The relative and absolute
      configurations of 1 were elucidated by the ROESY analysis and biogenesis pathway.
      All compounds were evaluated for their antibacterial activities against six
      pathogenic bacteria in vitro. Compounds 6 and 7 exhibited potent antibacterial
      activities against Bacillus cereus with the MIC values of 2.5 and 5 MUM,
      respectively.

PMID- 29212367
TI  - Assessment of Patient and Surgical Variables Including Residency Training Level
      on Adverse Events After Ureteroscopy for Ureteral Stones: A Multivariate
      Analysis.
AB  - PURPOSE: With advances in technology, ureteroscopy (URS) is increasingly utilized
      for the management of urolithiasis. Previous studies have attempted to
      characterize the post-operative complication and readmission rates relative to
      the technical difficulty of the procedure. There is limited data exploring the
      resident level of training and its effect on adverse outcomes in these cases. We
      review our experience with URS to create a model to predict factors, including
      resident experience, that affect rates of post-operative complications. MATERIALS
      AND METHODS: We reviewed ureteroscopies performed at our academic facility from
      January 2009 to December 2013. Ureteral-only stones were examined for
      demographics, stone characteristics, operative techniques, and resident training
      level. Post-operative adverse events requiring urology consultation, clinic or
      emergency department visits, hospital admission, prolonged post-operative
      hospitalization, or unplanned repeat surgery within 30 days of the procedure were
      identified and analyzed. RESULTS: Four hundred seventeen cases of URS for
      ureteral-only stones were included for study. We identified 53 (12.7%) involving
      an unexpected post-operative course. Several logistic regression models were
      created to make a predictive model of adverse events. One model found only lack
      of stone clearance to be significant for increasing the likelihood of an adverse
      event. A second model determined that no residency year showed higher odds of
      adverse outcomes. CONCLUSIONS: URS has increased in prevalence in recent years,
      but overall complication rates are low. Resident level of experience does not
      appear to impact adverse event rate. Stone clearance during initial surgery
      appears to be the most important in avoiding adverse events. Further expansion of
      the database over time will improve our ability to predict adverse outcomes in
      this common procedure.

PMID- 29212368
TI  - Impact of Variations in Prostatic Apex Shape on Apical Margin Positive Rate After
      Radical Prostatectomy: Robot-Assisted Laparoscopic Radical Prostatectomy vs Open
      Radical Prostatectomy.
AB  - AIM: To evaluate the effects of prostatic apex shape variations on positive
      apical margin (PAM) rate after radical prostatectomy (RP) by undertaking a
      comparative study of robot-assisted laparoscopic radical prostatectomy (RALP) vs
      open radical prostatectomy (ORP). PATIENTS AND METHODS: A total of 3324 cases of
      RP (1004 ORP and 2320 RALP) from January 2004 to March 2017 were retrospectively
      reviewed. All patients underwent preoperative MRI and the cohorts were stratified
      into four categories according to prostatic apical shape at the midsagittal
      plane. Between ORP and RALP groups, age, body mass index, preoperative prostate
      specific antigen (PSA), biopsy and pathological Gleason score (GS), clinical and
      pathological stage, and prostatic apex shapes were compared. Logistic regression
      analyses were performed to evaluate significant predictors of PAM. Propensity
      adjustments were undertaken before statistical analysis to minimize the lack of
      randomization. RESULTS: ORP and RALP groups showed no significant differences in
      age, body mass index, PSA, biopsy and pathological GS, clinical and pathological
      stage, as well as prostatic apical shape variations. The ORP group showed a PAM
      of 17.5% that was significantly higher than 12.3% of the RALP group (p < 0.001).
      Both groups showed the highest PAM with apical type 3, which is the apex covering
      the posterior aspect of membranous urethra (ORP 33.9%, RALP 28.5%). In unadjusted
      data, multiple logistic regression analysis showed that prostate apical type 3
      was a significant independent predictor of PAM, but other apex types were not.
      CONCLUSIONS: Prostate apical type 3 was a significant independent predictor of
      PAM. The RALP group showed better outcomes in terms of PAM compared with the ORP
      group. Preoperative MRI might be a potentially useful tool for preoperative
      designing of the surgical modalities.

PMID- 29212369
TI  - Chemical characterisation of the constituents of Eugenia protenta McVaugh and
      leishmanicidal activity of dimethylxanthoxylin.
AB  - The chemical study of Eugenia protenta McVaugh extracts performed by classical
      and high-performance liquid chromatography techniques and spectral methods has
      led to the identification of known triterpenoids, flavonoids and an acetophenone
      derivative (dimethylxanthoxylin). The effect of dimethylxanthoxylin on Leishmania
      (Leishmania) amazonensis was evaluated against the promastigotes forms after 96 h
      of treatment. Dimethylxanthoxylin reduced 57 and 59% of the promastigotes growth
      when treated with 50 and 100 MUg/mL solutions, respectively (IC50 117.35 MUg/mL
      or 52.3 MUM). Cytotoxicity experiments using MTT assays showed that this
      substance did not promote cell death after 24 h of treatment. Dimethylxanthoxylin
      was active on the promastigotes and could be a promising agent for treating
      leishmaniasis.

PMID- 29212371
TI  - Antioxidant activities and bioactive compounds of five Jalopeno peppers (Capsicum
      annuum) cultivars.
AB  - The present study was designed to evaluate the contents of different antioxidants
      compounds and their antioxidant activities in Jalopeno peppers (Capsicum annuum)
      cultivars (El Dorido, Grande, Tula, Sayula and El Rey) extracts. Free radical
      scavenging activity of Grande was recorded as high as 87% followed by El Dorido
      (83%). Results of reducing power (Fe3+ to Fe2+) showed that Grande (0.85%) and El
      Dorido (0.81%) fruit extract absorbance value were close to synthetic antioxidant
      BHT (0. 97%) obtained at100 MUg/mL. The results showed that total phenolic
      content of El Dorido and Grande were significantly higher compared to other
      Jalapeno pepper. Results indicated strong and positive correlation between
      antioxidant activity and carotenoids content (r = 0.75), vitamin C (r = 0.78) and
      total capsaicinoids (r = 0.84), respectively. The results of the antioxidant
      activity assays showed that the El Dorido and Grande had strongest antioxidant
      activity compared to other peppers cultivars in this study.

PMID- 29212370
TI  - Psychological interventions for coronary heart disease: Cochrane systematic
      review and meta-analysis.
AB  - Background Although psychological interventions are recommended for the
      management of coronary heart disease (CHD), there remains considerable
      uncertainty regarding their effectiveness. Design Systematic review and meta
      analysis of randomised controlled trials (RCTs) of psychological interventions
      for CHD. Methods The Cochrane Central Register of Controlled Trials, MEDLINE,
      EMBASE, CINAHL and PsycINFO were searched to April 2016. Retrieved papers,
      systematic reviews and trial registries were hand-searched. We included RCTs with
      at least 6 months of follow-up, comparing the direct effects of psychological
      interventions to usual care for patients following myocardial infarction or
      revascularisation or with a diagnosis of angina pectoris or CHD defined by
      angiography. Two authors screened titles for inclusion, extracted data and
      assessed risk of bias. Studies were pooled using random effects meta-analysis and
      meta-regression was used to explore study-level predictors. Results Thirty-five
      studies with 10,703 participants (median follow-up 12 months) were included.
      Psychological interventions led to a reduction in cardiovascular mortality
      (rfcelative risk 0.79, 95% confidence interval [CI] 0.63 to 0.98), although no
      effects were observed for total mortality, myocardial infarction or
      revascularisation. Psychological interventions improved depressive symptoms
      (standardised mean difference [SMD] -0.27, 95% CI -0.39 to -0.15), anxiety (SMD 
      0.24, 95% CI -0.38 to -0.09) and stress (SMD -0.56, 95% CI -0.88 to -0.24)
      compared with controls. Conclusions We found that psychological intervention
      improved psychological symptoms and reduced cardiac mortality for people with
      CHD. However, there remains considerable uncertainty regarding the magnitude of
      these effects and the specific techniques most likely to benefit people with
      different presentations of CHD.

PMID- 29212372
TI  - Crowdsourcing Evaluation of Ureteroscopic Videos Using the Post-Ureteroscopic
      Lesion Scale to Assess Ureteral Injury.
AB  - INTRODUCTION AND OBJECTIVES: We hypothesized that crowdsourcing assessments could
      be applied to the Postureteroscopic Lesion Scale (PULS) for ureteral injury.
      METHODS: At a single institution, we prospectively digitally recorded 14 ureters
      at the terminal portion of standard ureteroscopic procedures. Each recording was
      reviewed by 10 global experts to determine a mean PULS score. Following training,
      the Crowd-Sourced Assessment of Technical Skills, C-SATS(r) (C-SATS, Inc.,
      Seattle, WA) platform was used to obtain crowd-based reviews. The mean crowd PULS
      scores was determined using the linear mixed-effects (LME) model. The intraclass
      correlation coefficient (ICC) was calculated to measure the agreement among
      experts. Spearman's rank correlation (rho) was used to quantify the strength of
      the relationship between the crowd LME mean and the experts. RESULTS: Ten
      expert's reviews and 2100 layman reviews were obtained in 21 days and 49 hours,
      respectively. The ICC for the 10 experts was 0.68 (95% confidence interval 0.49,
      0.86). When the expert mean PULS was <1, the crowd scored those recordings at 1
      or greater. The highest scored recording by the experts was a 3.2, which the
      crowd scored at 2.25. The correlation between the crowd LME means and expert
      means across all videos was 0.70 (p = 0.0056) indicative of moderately strong
      agreement. CONCLUSION: In this initial application of crowd-sourced evaluation of
      ureteral injury, there was a moderately strong correlation between crowd and
      expert ratings. Refinement of the training, through exposure to the nuances of
      ureteral injuries, in particular for PULS <1 or >=3, may lead to better
      crowd/expert correlation. Compared to expert review, crowd data can be collected
      with much greater efficiency.

PMID- 29212373
TI  - Propensity Score-Matched Analysis Comparing Retrograde Intrarenal Surgery with
      Percutaneous Nephrolithotomy for Large Stones in Patients with a Solitary Kidney.
AB  - PURPOSE: To evaluate the clinical efficacy, safety, and cost of retrograde
      intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) in the
      treatment for large renal stones in patients with a solitary kidney. PATIENTS AND
      METHODS: In this study, 117 patients with a solitary kidney who had undergone
      PCNL or RIRS for renal stones larger than 2 cm between January 2010 and December
      2016 were retrospectively evaluated. The patients' demographic data, clinical
      characteristics, and perioperative outcomes were collected through a review of
      their medical records. Forty-three patients treated with PCNL were compared to 43
      patients treated with RIRS by propensity score-matched analysis. The stone-free
      rate, retreatment rate, complication rate, and efficacy quotient (EQ) were
      assessed in both groups. RESULTS: Initial stone-free rate of the PCNL group after
      a single procedure was significantly higher compared with the RIRS group (74.42%
      vs 34.88%, p < 0.001), whereas there was no significant difference in the final
      stone-free rate after repeated procedures (90.70% vs 88.37%, p = 0.713). PCNL had
      a significantly lower retreatment rate than RIRS (16.28% vs 63.79%, p < 0.001),
      and the PCNL group underwent fewer procedures than the RIRS group (p < 0.001).
      Thus, PCNL group had a higher EQ (78.00% vs 53.52%). Although cost per procedure
      of PCNL was significantly higher compared with RIRS (p < 0.001), the total costs
      were comparable. Complication rate of RIRS was lower compared with PCNL with no
      statistical significance (p = 0.193), and acute kidney injury rates were also
      comparable (PCNL vs RIRS: 13.95% vs 6.98%, p = 0.533). CONCLUSIONS: With fewer
      repeated surgical procedures, higher EQ, and comparable total costs, PCNL is
      recommended as the first choice for the treatment of large renal calculi in
      patients with a solitary kidney. As for specific indications such as
      anticoagulant drugs, RIRS is a safer choice with fewer complications and
      acceptable final stone-free rate.

PMID- 29212374
TI  - Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for
      Heparin Monitoring Using Multiple Nomograms.
AB  - The purpose of this study was to compare the performance of anti-factor Xa
      concentration versus activated partial thromboplastin time (aPTT) monitoring with
      multiple indication-specific heparin nomograms. This was a prospective,
      nonrandomized study with historical control at a large academic medical center. A
      total of 201 patients who received intravenous heparin in the cardiology units
      were included. The prospective cohort included patients (n = 101) with anti
      factor Xa (anti-Xa) monitoring, and the historical control group included
      patients (n = 100) who had aPTT monitoring. Patients in the prospective group had
      both anti-Xa and aPTT samples drawn, but anti-Xa was used for dosing adjustment.
      The anti-Xa cohort achieved a significantly faster time to therapeutic range ( P
      < .01) and required fewer dose adjustments per 24-hour period compared to the
      aPTT control ( P = .01). Results were consistent across heparin nomograms. The
      overall discordance rate between the 2 tests was 49%. No significant differences
      in clinical outcomes were observed. In summary, anti-Xa monitoring improved the
      time to therapeutic anticoagulation and led to fewer dose adjustments compared to
      the aPTT with multiple indication-based heparin nomograms.

PMID- 29212375
TI  - Evaluation of Monocyte to High-Density Lipoprotein Cholesterol Ratio in the
      Presence and Severity of Metabolic Syndrome.
AB  - Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a systemic
      inflammatory marker, and recently, it has been used quite commonly for the
      assessment of inflammation in cardiovascular disorders. The aim of the present
      study is to investigate the relevance of MHR as a marker to assess metabolic
      syndrome (MetS) and MetS severity in clinical practice. A total of 147 patients
      with MetS who were diagnosed according to National Cholesterol Education Program
      Adult Treatment Panel III criteria and 134 healthy controls, matched for age and
      gender, were included in our retrospective study. MHR values were 13.15 +/- 6.07
      for patients with MetS and 9.74 +/- 5.24 for the control group. MHR values of the
      patients were found to be statistically significantly higher than the control
      group ( P < .0001). MHR showed a significantly positive correlation with the
      severity of MetS ( r = .429; P < .0001). When patients with MetS were assessed
      with MHR in the study population, receiver-operating characteristic curve
      analysis yielded a cutoff value of 9.36 with a sensitivity of 72%, a specificity
      of 61%, and a P value <.0001. In logistic regression analyses of MetS with
      several variables, MHR remained as an independent predictor of MetS (95% CI:
      0.721-0.945, P = .005). MHR might be an available and useful inflammatory marker
      to evaluate patients with MetS and disease severity.

PMID- 29212376
TI  - A novel ion-activated in situ gelling ophthalmic delivery system based on kappa
      carrageenan for acyclovir.
AB  - The aim of this study was to prepare and evaluate ion-activated in situ gel
      ophthalmic drug delivery system based on kappa-carrageenan (KC), using acyclovir
      as a model drug, hydroxypropyl methylcellulose (HPMC) as the viscosity agent and
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the penetration enhancer. The two
      ternary phase diagrams exhibited the effect of K+ and Ca2+ on the sol-to-gel
      transition, which turned out that KC was more sensitive to K+. The optimal
      ophthalmic matrix (prepared from KC and HPMC) was optimized with in vitro drug
      release test. The apparent permeability coefficient of acyclovir under 2% HP-beta
      CD was found to have dramatically increased (2.16-ploid) than that of
      conventional eye drops (p < .05). The ion-activated in situ gel based on KC
      significantly delayed drug release and its bioavailability could be improved in
      comparison with the conventional eye drops. Hence, it has the potential to be a
      novel kind of ocular drug delivery system.

PMID- 29212378
TI  - Spanish adaptation of the edinburgh cognitive and behavioral amyotrophic lateral
      sclerosis screen (ECAS).
AB  - OBJECTIVE: Adaptation of the ECAS to the Spanish population. METHODS: The ECAS
      test was adapted and implemented in a random sample of 102 ALS patients. A test
      retest reliability of the instrument and internal consistency assessment were
      carried out. Its convergent validity was determined by comparing the ECAS screen
      with the ALS Cognitive Behavioural Screen (ALS-CBS), another standard tool.
      RESULTS: The Spanish adaptation of the ECAS scale preserves the statistical
      characteristics of the original version. Its analysis revealed a high internal
      consistency, similar to that of the original version. A significant correlation
      was found between the ECAS scale and the ALS-CBS, with the highest degree of
      correlation values shown at the Executive and Lack of empathy domains scales.
      Additionally, significant differences were observed between the scores obtained
      in ALS patients and healthy individuals. Furthermore, the analysis of the screen
      discrimination ability resulted acceptable. CONCLUSION: The results of this study
      prove that the Spanish adaptation of the ECAS scale preserves the internal
      consistency and construct validity of its original version.

PMID- 29212377
TI  - Gene Therapy for Bone Repair Using Human Cells: Superior Osteogenic Potential of
      Bone Morphogenetic Protein 2-Transduced Mesenchymal Stem Cells Derived from
      Adipose Tissue Compared to Bone Marrow.
AB  - Ex vivo regional gene therapy strategies using animal mesenchymal stem cells
      genetically modified to overexpress osteoinductive growth factors have been
      successfully used in a variety of animal models to induce both heterotopic and
      orthotopic bone formation. However, in order to adapt regional gene therapy for
      clinical applications, it is essential to assess the osteogenic capacity of
      transduced human cells and choose the cell type that demonstrates the best
      clinical potential. Bone-marrow stem cells (BMSC) and adipose-derived stem cells
      (ASC) were selected in this study for in vitro evaluation, before and after
      transduction with a lentiviral two-step transcriptional amplification system
      (TSTA) overexpressing bone morphogenetic protein 2 (BMP-2; LV-TSTA-BMP-2) or
      green fluorescent protein (GFP; LV-TSTA-GFP). Cell growth, transduction
      efficiency, BMP-2 production, and osteogenic capacity were assessed. The study
      demonstrated that BMSC were characterized by a slower cell growth compared to
      ASC. Fluorescence-activated cell sorting analysis of GFP-transduced cells
      confirmed successful transduction with the vector and revealed an overall higher
      but not statistically significant transduction efficiency in ASC versus BMSC
      (90.2 +/- 4.06% vs. 80.4 +/- 8.51%, respectively; p = 0.146). Enzyme-linked
      immunosorbent assay confirmed abundant BMP-2 production by both cell types
      transduced with LV-TSTA-BMP-2, with BMP-2 production being significantly higher
      in ASC versus BMSC (239.5 +/- 116.55 ng vs. 70.86 +/- 24.7 ng; p = 0.001).
      Quantitative analysis of extracellular deposition of calcium (Alizarin red) and
      alkaline phosphatase activity showed that BMP-2-transduced cells had a higher
      osteogenic differentiation capacity compared to non-transduced cells. When
      comparing the two cell types, ASC/LV-TSTA-BMP-2 demonstrated a significantly
      higher mineralization potential compared to BMSC/LV-TSTA-BMP-2 7 days post
      transduction (p = 0.014). In conclusion, this study demonstrates that
      transduction with LV-TSTA-BMP-2 can significantly enhance the osteogenic
      potential of both human BMSC and ASC. BMP-2-treated ASC exhibited higher BMP-2
      production and greater osteogenic differentiation capacity compared to BMP-2
      treated BMSC. These results, along with the fact that liposuction is an easy
      procedure with lower donor-site morbidity compared to BM aspiration, indicate
      that adipose tissue might be a preferable source of MSCs to develop a regional
      gene therapy approach to treat difficult bone-repair scenarios.

PMID- 29212379
TI  - Provision of rehabilitation services for children with disabilities living in low
      and middle-income countries: a scoping review.
AB  - BACKGROUND: Childhood disability is a growing global health priority. The purpose
      of this scoping review was to identify and summarize rehabilitation interventions
      used to support children with disabilities in low- and middle-income countries.
      METHODS: This scoping review involved a systematic search of electronic databases
      using a combination of subject headings and/or keywords related to child
      disability, rehabilitation, and low- and middle-income countries. Charting
      involved an iterative process whereby the full text of articles meeting the
      inclusion criteria were abstracted using a charting form. Data were charted
      according to pre-selected and emerging characteristics deemed relevant to the
      scoping review's purpose. RESULTS: Eighty-one articles were included in the final
      analysis. Forty-three articles explored the use of screening and/or diagnostic
      tools in identifying children with disabilities in low and middle income
      countries, and 38 articles evaluated rehabilitation services for these children.
      CONCLUSIONS: A number of rehabilitation strategies are available that have the
      potential to improve the identification of and outcomes for children with
      disabilities in low and middle income countries. Future research ought to advance
      the development, implementation, and evaluation of training programs for non
      rehabilitation specialists (e.g., doctors, nurses, and teachers), non-specialist
      community members (e.g., community health workers), and caregivers in the area of
      rehabilitation, and evaluate the effectiveness of rehabilitation interventions in
      improving participatory outcomes and quality of life for children with
      disabilities. Implications for Rehabilitation Additional research is needed to
      understand the influence of rehabilitation on personal factors (e.g., self
      efficacy and quality of life) and participation for children with disabilities.
      There is limited availability of experienced rehabilitation service providers,
      especially in rural areas, warranting additional research into the development
      and evaluation of non-specialist training programs, and the integration of
      rehabilitation concepts across health workforce education programs. Researchers
      from low and middle income countries appear to be underrepresented in published
      rehabilitation research, indicating a need to further promote the inclusion of
      this group through community-based participatory research.

PMID- 29212380
TI  - alphavbeta3 Integrin and fibronectin expressions and their relation to estrogen
      and progesterone during placentation in swine.
AB  - Mammalian pregnancy requires specific interactions between the conceptus and its
      mother that involve the endocrine system and adhesion molecules. The relation
      between adhesion molecules and their ligands at the fetal-maternal interface is
      crucial for developing a successful implantation. Progesterone (P4) and estrogen
      (E2) secreted by the porcine conceptus are required for the relation to be
      established. We investigated the expression of alphavbeta3 integrin and its
      ligand, fibronectin (FN), at the placental interface, and E2 and P4
      concentrations in both serum and maternal and fetal placental extracts during
      placentation in swine. Placental and serum samples of crossbred sows at 17, 30,
      60, 70, and 114 days gestation and no pregnant uteri were used. The presence of
      alphavbeta3 and FN were determined by immunohistochemistry, and E2 and P4 by
      chemiluminescence in homogenates of nonpregnant uterus (HoU), swine maternal
      placenta (HoPM), swine fetal placenta (HoPF) and serum. The expression of
      alphavbeta3 and FN increased at the interface at 17, 30 and 60 days gestation.
      Immunostaining decreased by 70 days. Serum E2 levels peaked at 17 days, then
      decreased, then increased again near term. The highest concentration of P4
      occurred in HoPF at 70 days gestation, then decreased coincident with a decline
      in integrin and FN expression at the placental interface. High P4 levels during
      swine gestation may regulate the expression of alphavbeta3 integrin and FN at the
      placental interface for up to 70 days gestation. Other adhesion molecules and
      their ligands likely maintain the fetal-placental interface after 70 days.

PMID- 29212381
TI  - Lowering side effects of NSAID usage in osteoarthritis: recent attempts at
      minimizing dosage.
AB  - INTRODUCTION: Osteoarthritis is a burdensome disease that causes progressive
      damage to articular cartilage. Non-steroidal anti-inflammatory drugs (NSAIDs) are
      one of the preferred treatments for symptomatic relief. However, NSAIDs can cause
      serious dose-dependent side effects, which has prompted experts to recommend the
      minimization of NSAID dosage. Areas covered: This review focuses on three broad
      strategies that are currently being investigated or implemented to minimize NSAID
      dosage: nano-formulation, encapsulation, and topical delivery. The benefits,
      challenges and current status of these methods are discussed. Expert opinion:
      Multiple strategies are under investigation to lower NSAID dosage. There is great
      potential in developing formulations that utilize more than one of these
      strategies together. However, there are challenges to developing these lower dose
      preparations. In order to maximize the clinical potential of the abundance of
      NSAIDs that are both available and being developed, there is a major need for
      additional clinical studies directly comparing safety and efficacy of different
      preparations.

PMID- 29212382
TI  - Gene Supplementation Rescues Rod Function and Preserves Photoreceptor and Retinal
      Morphology in Dogs, Leading the Way Towards Treating Human PDE6A-Retinitis
      Pigmentosa.
AB  - Mutations in the phosphodiesterase 6A gene (PDE6A) result in retinitis pigmentosa
      type 43 (RP43) and are responsible for about 4% of autosomal recessive RP. There
      is currently no treatment for this blinding condition. The aim of this project
      was to use a large animal model to test a gene supplementation viral vector
      designed to be translated for use in a clinical trial for the treatment of RP43.
      Seven Pde6a<sup>-/-</sup> puppies were given subretinal injections of an adeno
      associated viral vector serotype 2/8 delivering human PDE6A cDNA under control of
      a short rhodopsin promoter (AAV8-PDE6A). Three puppies received
      ~1x10<sup>11</sup> vg in one eye and four puppies ~5x10<sup>11</sup> vg/per eye
      with both eyes being injected in two animals. In vivo outcome measures included
      vision testing and electroretinography (ERG), as well as fundus and spectral
      domain - optical coherence tomography (SD-OCT) imaging. Some puppies were
      euthanized and their eyes processed for immunohistochemistry (IHC). All puppies
      had improved rod-mediated vision in the treated eye. ERGs showed improved rod
      mediated responses in the higher dose group but only in one of the lower dose
      group animals. Receptor+ (REC+) thickness was preserved and photoreceptor
      morphology improved in the treated retinal regions in all puppies. Treatment
      resulted in PDE6A transgene expression, accompanied by much increased levels of
      Pde6b, in rod outer segments in the injected retinal regions. There were several
      indications of improved retinal health in the PDE6A expressing regions including
      lack of abnormal cyclic GMP accumulation, appropriate rod opsin localization to
      the outer segments with a large reduction in mislocalization to other regions of
      the rod cell, and reduced Muller cell activation. Additionally, cone
      photoreceptors showed morphological improvement in the treated region with normal
      appearing inner and outer segments. The AAV8-PDE6A gene supplementation therapy
      restores rod vision in Pde6a<sup>-/-</sup> puppies and preserves retinal
      morphology. These positive outcomes are an important step towards a human
      clinical trial to treat PDE6A-RP.

PMID- 29212383
TI  - Menstrual migraine: a review of current and developing pharmacotherapies for
      women.
AB  - INTRODUCTION: Migraine is one of the most common neurological disorders in the
      general population. It affects 18% of women and 6% of men. In more than 50% of
      women migraineurs the occurrence of migraine attacks correlates strongly with the
      perimenstrual period. Menstrual migraine is highly debilitating, less responsive
      to therapy, and attacks are longer than those not correlated with menses.
      Menstrual migraine requires accurate evaluation and targeted therapy, that we aim
      to recommend in this review. Areas covered: This review of the literature
      provides an overview of currently available pharmacological therapies (especially
      with triptans, anti-inflammatory drugs, hormonal strategies) and drugs in
      development (in particular those acting on calcitonin gene-related peptide) for
      the treatment of acute migraine attacks and the prophylaxis of menstrual
      migraine. The studies reviewed here were retrieved from the Medline database as
      of June 2017. Expert opinion: The treatment of menstrual migraine is highly
      complex. Accurate evaluation of its characteristics is prerequisite to selecting
      appropriate therapy. An integrated approach involving neurologists and
      gynecologists is essential for patient management and for continuous updating on
      new therapies under development.

PMID- 29212384
TI  - Articular and subcutaneous adipose tissues of rheumatoid arthritis patients
      represent equal sources of immunoregulatory mesenchymal stem cells.
AB  - Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties,
      but their activity is dependent on signals provided by the local
      microenvironment. It is likely that highly inflammatory milieu of rheumatoid
      joint affects ASCs activity. To test this hypothesis, the function of rheumatoid
      ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from
      subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue
      (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin
      closure with sutures) were obtained from rheumatoid arthritis (RA) patients
      undergoing total knee joint replacement surgery. ASCs were isolated accordingly
      to the routinely applied procedure, expanded and treated or not with IFNgamma and
      TNF (10 ng/ml). To evaluate immunomodulatory properties of AT- and Sc-ASCs, co
      cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have
      been set. Proliferation of activated PBMCs (3H-thymidine incorporation method),
      secretion of IL-10 and IL-17A in co-culture supernatants (specific ELISA tests)
      and T regulatory FoxP3+ cells (Tregs) percentage have been evaluated (flow
      cytometry). Performed experiments demonstrated that ASCs from both sources have
      comparable properties. They suppress proliferation of activated PBMCs to the
      similar extent, induce IL-10 secretion by resting PBMCs and moderately induce
      generation of FoxP3+ Treg cells. Interestingly, both AT-ASCs and Sc-ASCs cause
      increase of IL-17A secretion by activated PBMCs as well as induce up-regulation
      of IL-6 concentration in co-culture supernatants. We demonstrated that AT-ASCs
      and Sc-ASCs obtained from RA patients possess similar immunomodulatory properties
      despite different localization and distinct cytokine milieu of tissue of origin.
      Our results indicate that ASCs derived from rheumatoid adipose tissues are not
      strongly immunosuppressive in vitro and that they may contribute to the
      pathogenesis of RA due to IL-17A secretion enhancement.

PMID- 29212385
TI  - Living environment and its relationship to depressive mood: A systematic review.
AB  - BACKGROUND AND AIMS: The notion that environment affects mental health has a long
      history; in this systematic review, we aimed to study whether the living
      environment is related to depressive mood. METHODS: We searched databases of
      PubMed, Scopus and Web of Science for population-based original studies prior to
      October 2016. We included studies that measured depressive symptoms or depression
      and had measures of urbanization, population density, aesthetics of living
      environment, house/built environment, green areas, walkability, noise, air
      pollution or services. RESULTS: Out of 1,578 articles found, 44 studies met our
      inclusion criteria. Manual searches of the references yielded 13 articles,
      resulting in 57 articles being included in the systematic review. Most of the
      studies showed statistically significant associations with at least one of the
      characteristics of living environment and depressive mood. House and built
      environment with, for example, poor housing quality and non-functioning, lack of
      green areas, noise and air pollution were more clearly related to depressive mood
      even after adjustment for different individual characteristics. On the contrary,
      the results in relation to population density, aesthetics and walkability of
      living environment, and availability of services and depressive mood were more
      inconsistent. CONCLUSION: Adverse house/built environment, including poor housing
      quality and non-functioning, lack of green spaces, noise and air pollution are
      related to depressive mood and should be taken into account during planning in
      order to prevent depressive mood.

PMID- 29212386
TI  - Efficacy and safety of sotagliflozin in treating diabetes type 1.
AB  - INTRODUCTION: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for
      use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the
      intestines resulting in reduced early phase glucose absorption and increased
      blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other
      agents as a result of decreased glucose absorption. The primary development
      effort to date has been in Type 1 diabetes. Areas covered: The published
      information on sotagliflozin is reviewed, along with the recent results of
      several pivotal Type 1 diabetes trials. Expert opinion: Sotagliflozin treatment
      lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic
      events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA
      at a higher rate than placebo treated patients. An additional safety issue arises
      from the as yet unknown potential risks in women of child bearing potential in
      whom DKA is of utmost concern. The sotagliflozin development program has now been
      extended to trials in Type 2 diabetes, and long term studies will be needed to
      assess the benefits and risks of the agent in comparison to other currently
      marketed SGLT2 inhibitors.

PMID- 29212387
TI  - Employee experience of workplace supervisor contact and support during long-term
      sickness absence.
AB  - PURPOSE: Workplace support is an important factor in promoting successful return
      to work. The purpose of this article is to examine relationships between
      supervisor contact, perceived workplace support and demographic variables among
      employees on long-term sickness absence. MATERIALS AND METHOD: Data were
      collected from 204 public employees at a municipality in Sweden who had been on
      long term sickness absence (60 days or more) using a 23 question survey
      instrument that collected information on demographic variables, supervisor
      contact and perceived workplace support. RESULTS: Most injured employees (97%)
      reported having contact with their supervisors during their sickness absence,
      with a majority (56%) reporting high levels of support, including early (58.6%)
      and multiple (70.7%) contacts. Most were pleased with amount of contact (68.9%)
      and the majority had discussed workplace accommodations (68.1%). Employees who
      self-initiated contact, felt the amount of contact was appropriate, had a
      personal meeting with their supervisors and discussed workplace adjustments
      reported experiencing higher levels of support from supervisors. CONCLUSIONS:
      Employees on long-term sickness absence appreciate contact from their supervisors
      and this is associated with perceived workplace support. However, the amount and
      employee experience of this contact is important. It needs to be perceived by
      employees as supportive, which includes a focus on strategies (e.g., work
      adjustment) to facilitate a return to work. Supervisor training is required in
      this area to support the return to work process. Implications for Rehabilitation
      Contact and support from workplace supervisors is important to workers on long
      term sickness absence. Employees appreciate frequent contact from supervisors
      during long-terms sickness absence. Employees appreciate a personal meeting with
      supervisors and the opportunity to discuss issues related to return to work such
      as work adjustment. Employers should provide training to supervisors on how to
      communicate and assist employees on long-term sickness absence.

PMID- 29212388
TI  - Good inter- and intraobserver reliability for assessment of the slip angle in 77
      hip radiographs of children with a slipped capital femoral epiphysis.
AB  - Background and purpose - The decision on and the outcome of treatment for a
      slipped capital femoral epiphysis (SCFE) depend on the severity of the slip. In
      2015, web-based registration was introduced into the Swedish Pediatric Orthopedic
      Quality (SPOQ) register. To determine whether the inclusion of commonly used
      methods in Sweden for radiographic measurement of SCFE (the calcar femorale [CF]
      method and the Billing method) is justified, we measured the inter- and
      intraobserver reliability of these 2 measurements. We also evaluated the
      internationally more commonly used head-shaft angle (HSA) method. Material and
      methods - 4 observers with different levels of experience with radiographic
      measurements analyzed 77 routine preoperative hip radiographs of children with
      SCFE. Inter- and intraobserver reliability was evaluated. Results - The
      interobserver reliability analysis for the 4 observers showed for CF an ICC of
      0.99 (CI 0.97-0.99) and for Billing an ICC of 0.99 (CI 0.98-0.99). The
      interobserver reliability analysis for 2 observers showed for HSA an ICC of 0.98
      (CI 0.97-0.99). Intraobserver reliability (2 observers) showed a mean difference
      below 1 degrees  for all 3 methods and with a 95% limit of agreement not
      exceeding +/-6.8 degrees . Interpretation - We found good reliability for both
      intra- and interobserver measurements of all 3 methods used for the assessment of
      the slip angle on routine preoperative lateral hip radiographs.

PMID- 29212389
TI  - Antimicrobial therapy of macrolide-resistant Mycoplasma pneumoniae pneumonia in
      children.
AB  - INTRODUCTION: Mycoplasma pneumoniae is an important cause of community-acquired
      pneumonia in children and young adolescents. Macrolides are recommended as the
      first-line therapy however, macrolide resistance rates in M. pneumoniae among
      children have been increasing substantially. Areas covered: This review focused
      on clinical characteristics and treatment of macrolide-resistant M. pneumoniae
      pneumonia in children. Expert commentary: Antibiotic choice should be based on in
      vitro activity, clinical efficacy and in consideration of potential adverse
      events. Macrolide resistance did not contribute to the clinical severity of M.
      pneumoniae pneumonia, but resistance may be an aggravating factor. Antibiotics
      may not be required for treatment in mild cases due to the self-resolving nature
      of M. pneumonia infection, regardless of macrolide resistance. In contrast,
      antibiotic treatment of severe cases of M. pneumoniae pneumonia is complicated.
      The clinical benefit of tetracyclines and fluoroquinolones has been shown in
      terms of shortening duration of symptoms and rapid defervescence in some reports.
      However, due to safety concerns regarding these two alternative antibiotics,
      clinicians should weigh the risks and benefits when choosing treatment options.
      Alternative antibiotics may be considered when patients remain febrile or when
      chest x-rays show deterioration at least 48-72 hours after macrolide treatment.

PMID- 29212390
TI  - Serratiopeptidase reduces the invasion of osteoblasts by Staphylococcus aureus.
AB  - Finding new strategies to counteract periprosthetic infection and implant failure
      is a main target in orthopedics. Staphylococcus aureus, the leading etiologic
      agent of orthopedic implant infections, is able to enter and kill osteoblasts, to
      stimulate pro-inflammatory chemokine secretion, to recruit osteoclasts, and to
      cause inflammatory osteolysis. Moreover, by entering eukaryotic cells,
      staphylococci hide from the host immune defenses and shelter from the
      extracellular antibiotics. Thus, infection persists, inflammation thrives, and a
      highly destructive osteomyelitis occurs around the implant. The ability of
      serratiopeptidase (SPEP), a metalloprotease by Serratia marcescens, to control S.
      aureus invasion of osteoblastic MG-63 cells and pro-inflammatory chemokine MCP-1
      secretion was evaluated. Human osteoblast cells were infected with staphylococcal
      strains in the presence and in the absence of SPEP. Cell proliferation and cell
      viability were also evaluated. The release of pro-inflammatory chemokine MCP-1
      was evaluated after the exposure of the osteoblast cells to staphylococcal
      strains. The significance of the differences in the results of each test and the
      relative control values was determined with Student's t-test. SPEP impairs their
      invasiveness into osteoblasts, without affecting the viability and proliferation
      of bone cells, and tones down their production of MCP-1. We recognize SPEP as a
      potential tool against S. aureus bone infection and destruction.

PMID- 29212391
TI  - Gene therapy successfully delays degeneration in a mouse model of PDE6A-linked
      retinitis pigmentosa (RP 43).
AB  - Retinitis pigmentosa type 43 (RP43) is a blinding disease caused by mutations in
      the gene for rod phosphodiesterase 6 alpha (PDE6A). The disease process begins
      with a dysfunction of rod photoreceptors, subsequently followed by a currently
      untreatable progressive degeneration of the entire outer retina. Aiming at a
      curative approach via PDE6A gene supplementation, we developed a novel adeno
      associated viral (AAV) vector for expression of the human PDE6A cDNA under
      control of the human rhodopsin promotor (rAAV8.PDE6A). In this study, we assessed
      the therapeutic efficacy of rAAV8.PDE6A in the Pde6anmf363/nmf363 mutant mouse
      model of RP43. All mice included in this study were treated with subretinal
      injections of the vector at 2 weeks after birth. The therapeutic effect was
      monitored at one month and at six months post injection. Biological function of
      the transgene was assessed in vivo by means of electroretinography (ERG). The
      degree of morphological rescue was investigated both in vivo using optical
      coherence tomography (OCT) and ex vivo by immunohistological stainings. We found
      that the novel rAAV8.PDE6A vector resulted in a stable and efficient expression
      of PDE6A protein in rod photoreceptors of Pde6anmf363/nmf363 mice following
      treatment at both the short and long-term time-points. The treatment led to a
      substantial morphological preservation of outer nuclear layer thickness, rod
      outer segment structure, and prolonged survival of cone photoreceptors for at
      least up to 6 months. Additionally, the ERG analysis confirmed a restoration of
      retinal function in a group of treated mice. Taken together, we provide
      successful proof-of-concept for the cross-species efficacy of the rAAV8.PDE6A
      vector developed for use in human patients. Importantly, our data show stable
      expression and rescue effects for a prolonged period of time, raising hope for
      future translational studies based on this approach.

PMID- 29212392
TI  - Multi-parametric magnetic resonance imaging monitoring patients in active
      surveillance for prostate cancer: a prospective cohort study.
AB  - OBJECTIVES: To evaluate the use of multi-parametric magnetic resonance imaging
      (mpMRI) and mpMRI guided biopsies (MRGB) for monitoring an active surveillance
      (AS) prostate cancer cohort. MATERIALS AND METHODS: One year after initial
      diagnostic TRUS guided biopsy (TRUS-bx), baseline mpMRI, and enrolment in an AS
      program patients underwent a one year follow-up comprising the usual TRUS-bx and
      an mpMRI. Prostate MRI lesions were scored on the five-point PIRADS scale version
      2. In cases without TRUS-bx progression, patients with PIRADS 4 or 5 lesions were
      scheduled for MRGB. Progression in TRUS-bx was defined as Gleason score (Gs) up
      grades, >3 tumor positive cores or a maximal cancer core length (MCCL) > 50%. In
      MRGB, Gs upgrade or a MCCL >=6 mm Gs 3 + 3 lesions were considered to reflect
      progression. PSA increase or progression in clinical T-classification alone was
      not considered clinical progression. RESULTS: 50 patients were included in the
      study. In total 10 (20%) patients had per definition progression at one year
      follow-up. Seven patients (7/50 = 14%) had clinical progression based on TRUS-bx.
      mpMRI identified seven newly emerged PIRADS 4 lesions. Three patients with PIRADS
      4 lesions had no sign of TRUS-bx progression, while MRGB revealed significant
      cancer (Gs 7 (3 + 4) and Gs 8 (3 + 5)). Consequently, seven patients underwent
      definitive treatment. Of these, six and four had a progression on MRI and TRUS
      bx, respectively. CONCLUSIONS: Our study suggests that mpMRI is at least equal to
      TRUS-bx in detecting progression at one year follow-up in prostate cancer
      patients undergoing active surveillance.

PMID- 29212393
TI  - "Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features"
      With Focal Spindle Cell Metaplasia.
AB  - "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features"
      (NIFTP) is a recent reclassification of the encapsulated follicular variant of
      papillary thyroid carcinoma, which is supposed to reflect its indolent clinical
      behavior and to prevent overtreatment of patients with this neoplasm. The
      diagnosis of NIFTP can only be made histologically on the surgical specimen
      according to specific inclusion and exclusion criteria, which requires the
      examination of the whole nodule and its capsule. Spindle cell proliferations,
      especially of follicular cell origin, arising within thyroid follicular neoplasms
      are very rare and may cause diagnostic difficulties. Few reports described
      spindle cell proliferations arising in follicular thyroid adenoma and papillary
      thyroid carcinoma. To the best of our knowledge, only one case has been reported
      in NIFTP so far. In this article, we report a unique case of NIFTP associated
      with a spindle cell proliferation that was characterized immunohistochemically.
      Specific issues related to this case are discussed.

PMID- 29212394
TI  - Management of dental caries among children: a look at the cost-effectiveness.
AB  - INTRODUCTION: Dental caries is the most prevalent non-communicative disease
      worldwide. Although the etiological factors are well known for years, reducing
      the number of decayed and missing teeth in children still remains as a barrier.
      Preventive and curative options are numerous but little is known about their
      economical advantages. Selecting the intervention that offers the best balance of
      effectiveness and financial resources becomes crucial in the current situation of
      budget restrictions worldwide. Areas covered: This expert review summarizes
      available evidence on cost-effectiveness analyses of preventive and curative
      measures to manage dental caries in children. Expert commentary: Preventive
      measures have been more extensively studied than dental caries treatment. Only
      water fluoridation and tooth brushing are well-established as cost-effective
      preventive approaches. Despite the increasing number of cost analysis treatment
      studies in the literature, most of them focus on the cost description, with no
      correlation to the intervention effectiveness. There is a current need of well
      designed and well-reported cost-effectiveness regarding dental caries management.

PMID- 29212395
TI  - Prenatal prediction of small-for-gestational age neonates using MR imaging:
      comparison with conventional 2D ultrasound.
AB  - PURPOSE: The purpose of this study is to evaluate the performance of estimating
      fetal weight (EFW) using magnetic resonance (MR) imaging as compared with two
      dimensional (2D) ultrasound (US) in the prediction of small-for-gestational age
      neonates (SGA). MATERIALS AND METHODS: Written informed consent was obtained for
      this Ethical Committee approved study. Between March 2011 and May 2016, women
      with singleton pregnancies underwent US-EFW and MR-EFW within 48 h before
      delivery. US-EFW was based on Hadlock et al. and MR-EFW on the formula described
      by Backer et al. after planimetric measurement of the fetal body volume (FBV).
      Our outcome measure was performance in prediction of small-for-gestational age
      neonates by MR imaging versus US-EFW, using receiver-operating characteristic
      (ROC) curves. RESULTS: Two hundred and seventy women were included in the study
      with 18 newborns (6.7%) of birthweight <=10th, 12 (4.5%) <= 5th and 7 (2.6%) <=
      3rd centile. The area under the ROC curve for prediction of birthweight <=10th
      centile by prenatal MR imaging was significantly better than by US (difference
      between the AUROC = 0.060, p = .01; standard error = 0.023). Similarly, the area
      under the ROC curve for prediction of birthweight <=5th centile by prenatal MR
      imaging was significantly better than by US (difference between the AUROC =
      0.019, p = .03; standard error = 0.009). Finally, there was no significant
      difference between the areas under the ROC curve for the prediction of
      birthweight <=3rd centile between the two imaging modalities (difference between
      the AUROC = 0.021, p = .13; standard error = 0.014). CONCLUSION: MR-EFW performed
      immediately prior to delivery predicts SGA neonates significantly better than US
      EFW.

PMID- 29212396
TI  - Dysautonomia in the pathogenesis of migraine.
AB  - INTRODUCTION: Migraine is a common complex neurological disorder involving
      multiple brain areas that regulate autonomic, affective, cognitive, and sensory
      functions. This review explores autonomic nervous system (ANS) dysfunction in
      migraine headache sufferers. Areas covered: Reference material for this review
      was obtained through PubMed searches. Migraine attacks can present with up to 4
      phases (premonitory, aura, headache, postdrome) each with distinguishable signs
      and symptoms. Altered ANS tone can be found from the premonitory through the
      postdrome phases. Features of the migraine attack that are indicative of altered
      autonomic function, which include nausea, vomiting, diarrhea, polyuria, eyelid
      edema, conjunctival injection, lacrimation, nasal congestion, and ptosis, are
      discussed and putative mechanisms explored. In addition, alteration of ANS
      function by endogenous and exogenous stressors, such as bright lights, hunger,
      poor sleep quality, menses, and special dietary components is discussed. The
      influence of currently employed pharmacological treatments on altered autonomic
      function during the migraine attack is explored. Expert commentary: Migraine
      related alterations in ANS function have a complex pattern, but, in general, an
      imbalance occurs between sympathetic and parasympathetic tone. Through an
      improved understanding the role of autonomic changes in pathogenesis of migraine,
      it may be possible to develop even more effective treatments for migraine
      sufferers.

PMID- 29212397
TI  - Growth and neurodevelopment in very preterm infants receiving a high enteral
      volume-feeding regimen - a population-based cohort study.
AB  - AIM: The aim of this study is to evaluate a feeding regimen routinely providing
      >180 ml/kg/d fortified human milk to very preterm infants and impact on in
      hospital growth, osteopenia, and neurodevelopment. METHOD: Retrospective
      population-based descriptive study of infants <30-week gestation admitted within
      24 h of birth and discharged during the 6-year period 2005-2010. Growth and
      neurodevelopment was assessed until 2 years corrected age, and cerebral palsy up
      to 4 years corrected age Results: Ninety-nine infants below 30-week gestation
      were admitted within 24 h of birth during the 6-year period, of which 84 (85%)
      survived to discharge. Two infants had surgical necrotizing enterocolitis, both
      survived to 2 years follow up. Seventy-eight infants (mean 27 weeks) had complete
      growth data until discharge. Full enteral feeds were tolerated after mean 10 d.
      Average milk volumes were 193 ml/kg/d from 15 to 42 d of life. Rates of weight
      below 10th centile were 10% at birth and 14% at discharge. Head circumference Z
      scores were stable from birth to discharge. Blood values did not indicate
      osteopenia. Increasing head circumference Z-scores were associated with improved
      language development. CONCLUSIONS: This high enteral feeding volume regimen was
      associated with low rates of in-hospital growth restriction and good head growth.
      High enteral volume intake seems safe and may improve nutritional status of very
      preterm infants.

PMID- 29212398
TI  - Prediction of neonatal respiratory distress syndrome via pulmonary artery Doppler
      examination.
AB  - OBJECTIVE: We aimed with this study to evaluate the role of pulmonary artery
      acceleration time to ejection time ratio (PATET) in the prediction of respiratory
      distress syndrome (RDS) in preterm neonates. MATERIALS AND METHODS: In this
      prospective cohort study, 105 singleton pregnant women with no congenital
      abnormalities and pregnancy complications who delivered before 37 weeks of
      gestational age were included. All the patients underwent ultrasound examination
      to obtain fetal pulmonary artery Doppler. 15 patients were excluded from the
      study as they did not give birth within 3 days subsequent to ultrasound
      examination, or inadequate Doppler measurements. After delivery the neonates were
      grouped according to diagnosis of RDS as RDS + and RDS-. RESULTS: One hundred
      five women met the inclusion criteria. Regarding the Doppler findings; only the
      PATET ratio was significantly different between the groups (0.2965 +/- 0.042
      versus 0.386 +/- 0.068 p < .001, Z = -5.206). There was an inverse correlation
      between the diagnosis of RDS in the neonates and the PATET values, even after
      adjusted for gestational age estimated fetal weight and fetal gender (r = -0.52
      and p = .0017). A cut-off value of 0.327 provided optimal specificity of 77.1%, a
      sensitivity of 90.9%, a negative predictive value of 95.4%, and a positive
      predictive value 52.7%. CONCLUSIONS: In consideration of these results fetal
      PATET ratio is a promising noninvasive tool to predict RDS in cases of preterm
      deliveries.

PMID- 29212400
TI  - Cervical pessaries for the prevention of preterm birth: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The objective of this study is to evaluate the effectiveness and
      safety of cervical pessaries for the prevention of preterm birth. METHODS: We
      searched PubMed, Embase, Web of Science, and other sources from inception to July
      2016. This analysis referred to pregnant women with singleton/multiple viable
      fetus/fetuses, with or without cervical pessary placement. RESULTS: Six
      randomized control trials and five cohort studies involving 3911 participants
      were included. Overall, cervical pessary placement was slightly associated with
      the decrease of spontaneous delivery less than 34 weeks (relative risk 0.65 [95%
      CI: 0.44-0.96]) and increased gestational age at delivery (weighted mean
      difference 1.03 weeks [95% CI: 0.37-1.70]) in multiple pregnancies, but not with
      poor perinatal outcomes. Pessary placement in singleton pregnancies did not show
      any difference. A planned subgroup analysis showed multiple pregnancies with
      shorter cervical length (<=25 mm) had a longer prolongation of pregnancy
      (weighted mean difference 2.08 weeks [95% CI: 1.35-2.82]). CONCLUSION: This meta
      analysis suggested pessary placement could slightly reduce the rate of
      spontaneous preterm delivery before 34 weeks, and increase gestational age at
      delivery in multiple pregnancies, but not in singleton pregnancies. More studies
      of high quality with detailed records are urgent to confirm the efficacy of this
      procedure.

PMID- 29212399
TI  - Conservative management of CIN2: National Audit of British Society for Colposcopy
      and Cervical Pathology members' opinion.
AB  - There is no doubt that organised cervical screening programmes have significantly
      reduced the rates of cervical cancer by detection and treatment of high-grade
      cervical intraepithelial neoplasia (CIN2, CIN3). National UK guidelines do not
      differentiate between CIN2 and CIN3 as separate entities and recommend treatment
      for both, although a degree of uncertainty exists regarding the natural history
      of CIN2. This national survey of British Society for Colposcopy and Cervical
      Pathology members aimed to assess attitudes towards conservative management (CM)
      of CIN2 in the UK and identify potential selection criteria. In total, 511
      members responded (response rate 32%); 55.6% offered CM for selective cases;
      12.4% for all cases; 16.4% had formal guidelines. Most agreed age group was
      >40yrs (83%), HPV 16/18 positive (51.4%), smoking (60%), immuno-compromise
      (74.2%), and large lesion size (80.8%) were relative contraindications for CM.
      75.9% favoured six-monthly monitoring, with 80.2% preferring excisional treatment
      for persistent high-grade disease. Many UK colposcopists manage CIN2
      conservatively without formal guidelines. Potential selection criteria should be
      investigated by a multicentre study. Impact statement Although anecdotally some
      colposcopists manage many women with CIN2 conservatively, this National Audit of
      British Society for Colposcopy and Cytopathology members, we believe, is the
      first time this has been formally recorded. The survey assesses current attitudes
      towards conservative management (CM) of CIN2 and seeks to identify potential
      selection criteria that could be used to identify suitable women. It received
      over 500 responses and significantly, identified many colposcopists recommending
      CM of CIN2 for patients despite the lack of any formal guidance regarding this
      approach. The greater majority of respondents were keen to consider participating
      in a multicentre trial on CM of CIN2 targeting the UK screening population (25-64
      years). The paper has international relevance as ACOG and ASCCP have recently
      changed their guidance for the management of CIN2 in younger women and now
      recommend CM with monitoring rather than first line ablative or excisional
      treatment due to concerns regarding overtreatment, especially in women who have
      not yet completed their family.

PMID- 29212401
TI  - Evaluating the effects of administration of 25-hydroxyvitamin D supplement on
      serum anti-mullerian hormone (AMH) levels in infertile women.
AB  - The aim of the study was to evaluate the effects of administration of 25
      hydroxyvitamin D [25(OH) D] on serum antimullerian hormone (AMH) levels in
      infertile women. The study was performed as a non-randomized clinical trial on 30
      infertile women who had low serum level of both 25(OH) D and anti-mullerian
      hormone. Vitamin D was prescribed 50,000 IU weekly for up to three months for all
      eligible participants. Serum levels of both 25(OH) D and AMH have increased
      significantly after treatment with 25(OH) D. There was a significant correlation
      between serum levels of 25(OH) D after treatment with AMH (p = .029, OR = 2.9, CI
      95% = 2.7-5.5). Mean AMH level after treatment was higher in women with
      sufficient 25(OH) D, than women with insufficient 25(OH) D (1.048 +/- 0.644 vs.
      0.513 +/- 0.284 ng/ml), which shows a significant difference (p = .043). Also,
      after treatment, in women with mean AMH level of >0.7 ng/ml (19 women), mean
      level of 25(OH) D was higher than in women with mean AMH level of <0.7 ng/ml (11
      women) (59.332 +/- 21.751 vs. 38.881 +/- 17.281 ng/ml, p = .013). This means that
      higher levels of 25(OH) D are accompanied with higher levels of AMH. In
      conclusions with administration and increasing the amount of vitamin D serum
      levels, the serum levels of AMH have increased.

PMID- 29212402
TI  - Translocator protein agonist Ro5-4864 alleviates neuropathic pain and promotes
      remyelination in the sciatic nerve.
AB  - Our previous study reported the translocator protein to play a critical role in
      neuropathic pain and the possible mechanisms in the spinal cord. However, its
      mechanism in the peripheral nervous system is poorly understood. This study was
      undertaken to explore the distribution of translocator protein in the dorsal root
      ganglion and the possible mechanisms in peripheral nervous system in a rat model
      of spared nerve injury. Our results showed that translocator protein was
      activated in dorsal root ganglion after spared nerve injury. The translocator
      protein signals were primarily colocalized with neurons in dorsal root ganglion.
      A single intrathecal (i.t.) injection of translocator protein agonist (7-chloro-5
      4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiaze-pine-2) (Ro5-4864)
      exerted remarkable analgesic effect compared with the spared nerve injury group (
      P < 0.01). After i.t. administration of 2 ug Ro5-4864 on day 3, the expression of
      translocator protein in ipsilateral dorsal root ganglion was significantly
      increased on day 7( P < 0.01) but decreased on day 14 ( P < 0.05) compared with
      the same point in time in the control group. The duration of translocator protein
      activation in dorsal root ganglion was remarkably shortened. Ro5-4864 also
      inhibited the activation of phospho-extracellular signal-regulated kinase 1(p
      ERK1) ( P < 0.01), p-ERK2 (D7: P < 0.01, D14: P < 0.05), and brain-derived
      neurotrophic factor ( P < 0.05) in dorsal root ganglion. Meanwhile, i.t.
      administration of 2 ug Ro5-4864 on day 3 further accelerated the expression of
      myelin protein zero(P0) and peripheral myelin protein 22 (PMP22). Our results
      suggested Ro5-4864 could alleviate neuropathic pain and attenuate p-ERK and brain
      derived neurotrophic factor activation in dorsal root ganglion. Furthermore, Ro5
      4864 stimulated the expression of myelin regeneration proteins which may also be
      an important factor against neuropathic pain development. Translocator protein
      may present a novel target for the treatment of neuropathic pain both in the
      central and peripheral nervous systems.

PMID- 29212404
TI  - Low-Grade Fibromyxoid Sarcoma With Striking Zonation.

PMID- 29212405
TI  - A Description of a New Continuous Physiological Index in Traumatic Brain Injury
      Using the Correlation between Pulse Amplitude of Intracranial Pressure and
      Cerebral Perfusion Pressure.
AB  - To describe a new continuous index of physiologic measurement in a traumatic
      brain injury (TBI) population, the moving correlation coefficient between
      intracranial pressure (ICP) pulse amplitude (AMP) and cerebral perfusion pressure
      (CPP), which we refer to as RAC. We use patient examples of sustained
      intracranial hypertension, systemic arterial hypotension, and plateau waves, as
      well as the retrospective analysis of 358 non-decompressive craniectomy (DC) TBI
      patients with high-frequency ICP and arterial blood pressure data, to explore the
      relationships of this new index, RAC, with AMP, ICP, CPP, RAP (correlation
      coefficient between AMP and ICP), pressure reactivity index (PRx), and pulse
      amplitude index (PAx). We compared the RAC-CPP relationship to that observed
      between CPP and both PRx and PAx. RAC displays temporal responsiveness to
      sustained increased ICP, arterial hypotension, and plateau waves, with positive
      values found during episodes of high ICP and low CPP. Analysis of AMP versus CPP
      and AMP versus ICP relationships in data from the entire non-DC cohort show lower
      breakpoints for AMP/CPP at CPP = 40 mm Hg and upper breakpoints for AMP/ICP at
      ICP = 50-60 mm Hg. RAC trends to positive values with increasing ICP,
      particularly with ICP values above the peak in AMP (ICP >50 mm Hg), though its
      interpretation requires concomitant interpretation of AMP, RAP, and PRx/PAx to
      determine contributions of compensatory reserve and cerebrovascular
      responsiveness to the changes observed in RAC. There is a parabolic relationship
      between RAC versus CPP, with trends toward positive RAC values near (and beyond)
      limits for low and high CPPs, suggesting that RAC may be used in the
      determination of optimum CPP. RAC appears to carry information regarding both
      cerebrovascular responsiveness and cerebral compensatory reserve. This
      contributes to RAC's uniqueness and complex interpretation. Further prospective,
      clinical studies of RAC in CPP optimum estimation and outcome prediction in TBI
      are required.

PMID- 29212403
TI  - A simple and fast method to image calcium activity of neurons from intact dorsal
      root ganglia using fluorescent chemical Ca2+ indicators.
AB  - Chemical calcium indicators have been commonly used to monitor calcium (Ca2+)
      activity in cell bodies, i.e., somata, of isolated dorsal root ganglion neurons.
      Recent studies have shown that dorsal root ganglion somata play an essential role
      in soma-glia interactions and actively participate in the transmission of
      nociceptive signals. It is therefore desirable to develop methods to study Ca2+
      activity in neurons and glia in intact dorsal root ganglia. In our previous
      studies, we found that incubation of intact dorsal root ganglia with
      acetoxymethyl dye resulted in efficient Ca2+ dye loading into glial cells but
      limited dye loading into neurons. Here, we introduce a useful method to load Ca2+
      dyes in intact dorsal root ganglion neurons through electroporation. We found
      that electroporation greatly facilitated loading of Fluo-4 acetoxymethyl, Oregon
      green bapta-1-488 acetoxymethyl, and Fluo-4 pentapotassium salt into dorsal root
      ganglion neurons. In contrast, electroporation did not further facilitate dye
      loading into glia. Using electroporation followed by incubation of acetoxymethyl
      form Ca2+ dye, we can load acetoxymethyl Ca2+ dye well in both neurons and glia.
      With this approach, we found that inflammation induced by complete Freund's
      adjuvant significantly increased the incidence of neuron-glia interactions in
      dorsal root ganglia. We also confirmed the actions of capsaicin and morphine on
      Ca2+ responses in dorsal root ganglion neurons. Thus, by promoting the loading of
      Ca2+ dye in neurons and glia through electroporation and incubation, Ca2+
      activities in neurons and neuron-glia interactions can be well studied in intact
      dorsal root ganglia.

PMID- 29212406
TI  - EEG Measurement of Emotion Processing in Children with Daytime Urinary
      Incontinence.
AB  - OBJECTIVE: Daytime urinary incontinence (DUI) is common in childhood. The aim of
      the study was to neurophysiologically analyse the central emotion processing in
      children with DUI. METHOD: In 20 children with DUI (mean age 8.1 years, 55 %
      male) and 20 controls (mean age 9.1 years, 75 % male) visual event-related
      potentials (ERPs) were recorded after presenting emotionally valent (80 neutral,
      40 positive, and 40 negative) pictures from the International Affective Picture
      System (IAPS) as an oddball-paradigm. All children received a full organic and
      psychiatric assessment. RESULTS: Children with DUI did not differ significantly
      from controls regarding responses to emotional pictures in the frontal, central,
      and parietal regions and in the time intervals 250-450 ms, 450-650 ms, and 650
      850 ms after stimulus onset. The patient group had more psychological symptoms
      and psychiatric comorbidities than the control group. CONCLUSIONS: EEG responses
      to emotional stimuli are not altered in children with DUI. Central emotion
      processing does not play a major role in DUI. Further research, including a
      larger sample size, a more homogeneous patient group (regarding subtype of DUI)
      or brain imaging techniques, could reveal more about the central processing in
      DUI.

PMID- 29212408
TI  - Aperture Synthesis Shows Perceptual Integration of Geometrical Form Across
      Saccades.
AB  - We investigated the perceptual bias in perceived relative lengths in the Brentano
      version of the Muller-Lyer arrowheads figure. The magnitude of the bias was
      measured both under normal whole-figure viewing condition and under an aperture
      viewing condition, where participants moved their gaze around the figure but
      could see only one arrowhead at a time through a Gaussian-weighted contrast
      window. The extent of the perceptual bias was similar under the two conditions.
      The stimuli were presented on a CRT in a light-proof room with room-lights off,
      but visual context was provided by a rectangular frame surrounding the figure.
      The frame was either stationary with respect to the figure or moved in such a
      manner that the bias would be counteracted if the observer were locating features
      with respect to the frame. Biases were reduced in the latter condition. We
      conclude that integration occurs over saccades, but largely in an external visual
      framework, rather than in a body-centered frame using an extraretinal signal.

PMID- 29212407
TI  - RNA interference-based functional knockdown of the voltage-gated potassium
      channel Kv7.2 in dorsal root ganglion neurons after in vitro and in vivo gene
      transfer by adeno-associated virus vectors.
AB  - Activation of the neuronal potassium channel Kv7.2 encoded by the KCNQ2 gene has
      recently been shown to be an attractive mechanism to inhibit nociceptive
      transmission. However, potent, selective, and clinically proven activators of
      Kv7.2/Kv7.3 currents with analgesic properties are still lacking. An important
      prerequisite for the development of new drugs is a model to test the selectivity
      of novel agonists by abrogating Kv7.2/Kv7.3 function. Since constitutive knockout
      mice are not viable, we developed a model based on RNA interference-mediated
      silencing of KCNQ2. By delivery of a KCNQ2-specific short hairpin RNA with adeno
      associated virus vectors, we completely abolished the activity of the specific
      Kv7.2/Kv7.3-opener ICA-27243 in rat sensory neurons. Results obtained in the
      silencing experiments were consistent between freshly prepared and cryopreserved
      dorsal root ganglion neurons, as well as in dorsal root ganglion neurons
      dissociated and cultured after in vivo administration of the silencing vector by
      intrathecal injections into rats. Interestingly, the tested associated virus
      serotypes substantially differed with respect to their transduction capability in
      cultured neuronal cell lines and primary dorsal root ganglion neurons and the in
      vivo transfer of transgenes by intrathecal injection of associated virus vectors.
      However, our study provides the proof-of-concept that RNA interference-mediated
      silencing of KCNQ2 is a suitable approach to create an ex vivo model for testing
      the specificity of novel Kv7.2/Kv7.3 agonists.

PMID- 29212409
TI  - A comparison of early and late treatments on allodynia and its chronification in
      experimental neuropathic pain.
AB  - Background Surgeries causing nerve injury can result in chronic neuropathic pain,
      which is clinically managed by using antidepressant or anticonvulsant drugs.
      Currently, there is a growing interest for investigating preemptive treatments
      that would prevent this long-term development of neuropathic pain. Our aim was to
      compare analgesic drugs using two distinct treatment modalities: either treatment
      onset at surgery time or following a couple of weeks of neuropathic pain. Methods
      In male C57BL/6J mice, neuropathic pain was induced by cuffing the sciatic nerve,
      and allodynia was assessed using von Frey filaments. We tested the effect of
      anticonvulsants (gabapentin 10 mg/kg and carbamazepine 40 mg/kg), antidepressants
      (desipramine 5 mg/kg, duloxetine 10 mg/kg, and fluoxetine 10 mg/kg),
      dexamethasone (2 mg/kg), and ketamine (15 mg/kg). Drugs were injected daily or
      twice a day, starting either at surgery time or on day 25 postsurgery (15 days of
      treatment for antidepressants and 10 days for other drugs). Results Ketamine was
      the only effective treatment during the early postsurgical period. Although early
      anticonvulsant treatment was not immediately effective, it prevented
      chronification of allodynia. When treatments started at day 25 postsurgery,
      desipramine, duloxetine, and anticonvulsants suppressed the mechanical allodynia.
      Conclusions Our data show that allodynia measured in experimental neuropathic
      pain model likely results from a combination of different processes (early vs.
      late allodynia) that display different sensitivity to treatments. We also propose
      that early anticonvulsant treatment with gabapentin or carbamazepine may have a
      prophylactic effect on the chronification of allodynia following nerve injury.

PMID- 29212410
TI  - Exploring Perceived Barriers to Medication Adherence and the Use of Mobile
      Technology in Underserved Patients With Chronic Conditions.
AB  - BACKGROUND AND OBJECTIVE: Evidence suggests that the prevalence of medication
      nonadherence is greater in medically underserved, low-income communities. There
      is paucity of qualitative data examining the potential use of mobile health
      (mHealth) in underserved patients. This study aimed to explore barriers to
      medication adherence and identify opportunities and challenges for the potential
      use of mHealth adherence interventions in an underserved population. METHODS: A
      qualitative cross-sectional focus group was conducted. Focus groups were
      conducted with underserved patients recruited at a federally qualified health
      center. The Health Belief Model was used as theoretical framework to develop the
      focus group guide. Audio-recorded data were transcribed and thematically analyzed
      to identify common themes across the data set. RESULTS: Seventeen patients
      participated in 4 focus groups. Findings were organized by the following themes:
      (1) perceived barriers to medication adherence, (2) everyday practices used to
      improve medication adherence, and (3) perceived benefits and barriers to
      technology use. Use of text messages seemed beneficial; however, not carrying a
      phone always was a significant barrier for patients. Some patients expressed
      willingness to try smartphone applications but stated that they would not be able
      to afford them. Changes in daily routine and complexity of medication regimens
      were seen as barriers to medication adherence. CONCLUSIONS: Findings underscore
      the importance of considering diverse experiences when engaging patients in
      mHealth for medication adherence. Providing patient-centered approaches to assist
      patients construct their individualized medication adherence strategies may lead
      to better outcomes.

PMID- 29212412
TI  - Enhanced anticancer potency by thermo/pH-responsive PCL-based magnetic
      nanoparticles.
AB  - Great efforts have been made to develop drug carriers with the aim of providing
      predictable therapeutic response. Moreover, combination therapies have become
      promising strategies for clinical cancer treatment with synergistic effects. The
      present study purposed to develop a new stimuli-responsive paramagnetic
      nanocarrier for the intracellular co-delivery of doxorubicin (DOX) and
      methotrexate (MTX) to the MCF7 cell line. A novel thermo/pH-sensitive amphiphilic
      paramagnetic nanocomposite comprised of hydrophobic and biodegradable PCL
      segments and a hydrophilic biocompatible P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) block
      was designed and synthesized by combining the ring opening and free radical
      polymerization methods. The structure and physic-chemical characterization of
      synthesized nanoparticles and intermediates were studied and revealed using FTIR,
      HNMR, CNMR, SEM, EDX, TGA, and VSM techniques. DOX and MTX on a nanocarrier
      achieved 95.04 and 97.29% encapsulation efficiency, respectively. The dual drug
      release profile revealed tumor niche-assisted release behavior (more drug release
      was observed at a temperature of 41  degrees C and pH <= 5.4). The antitumor
      ability of the DOX/MTX-loaded nanocomposite was significantly higher than that of
      free drugs, confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR
      analysis on MCF7 cell lines. Furthermore, the cytotoxicity assay of a nanocarrier
      to the MCF7 cell line revealed its suitability as an anticancer drug nanocarrier.
      The results indicated that this engineered dual anticancer drug delivery system
      ensures increased antitumor activity as well as decreased toxicity in comparison
      with the free drugs.

PMID- 29212413
TI  - A lower extremity strength-based profile of NCAA Division I women's basketball
      and gymnastics athletes: implications for knee joint injury risk assessment.
AB  - This study aimed to provide a comprehensive strength-based physiological profile
      of women's NCAA Division I basketball and gymnastic athletes; and to make sport
      specific comparisons for various strength characteristics of the knee flexor and
      extensor muscles. A focus on antagonist muscle balance (hamstrings-to-quadriceps
      ratios, H:Q) was used to elucidate vulnerabilities in these at-risk female
      athletes. Fourteen NCAA Division I women's basketball and 13 gymnastics athletes
      performed strength testing of the knee extensors and flexors. Outcome measures
      included absolute and relative (body mass normalised) peak torque (PT), rate of
      torque development at 50, 100, 200 ms (RTD50 etc.) and H:Q ratios of all
      variables. The basketball athletes had greater absolute strength for all
      variables except for isokinetic PT at 240 degrees s-1 and isometric RTD50 for the
      knee extensors. Gymnasts showed ~20% weaker body mass relative concentric PT for
      the knee flexors at 60 and 120 degrees .s-1, and decreased conventional H:Q
      ratios at 60 and 240 degrees .s-1 (~15%). These findings suggest that collegiate
      level gymnastics athletes may be prone to increased ACL injury risk due to
      deficient knee flexor strength and H:Q strength imbalance. Coaches may use these
      findings when implementing injury prevention screening and/or for individualised
      strength training programming centered around an athletes strength-related
      deficits.

PMID- 29212414
TI  - A suite of DNA methylation markers that can detect most common human cancers.
AB  - Cancer-specific DNA methylation from the tumor derived fraction of cell free DNA
      found in blood samples could be used for minimally invasive detection and
      monitoring of cancer. The knowledge of marker regions with cancer-specific DNA
      methylation is necessary to the success of such a process. We analyzed the
      largest cancer DNA methylation dataset available-TCGA Illumina
      HumanMethylation450 data with over 8,500 tumors-in order to find cancer-specific
      DNA methylation markers for most common human cancers. First, we identified
      differentially methylated regions for individual cancer types and those were
      further filtered against data from normal tissues to obtain marker regions with
      cancer-specific methylation, resulting in a total of 1,250 hypermethylated and
      584 hypomethylated marker CpGs. From hypermethylated markers, optimal sets of six
      markers for each TCGA cancer type were chosen that could identify most tumors
      with high specificity and sensitivity [area under the curve (AUC): 0.969-1.000]
      and a universal 12 marker set that can detect tumors of all 33 TCGA cancer types
      (AUC >0.84). In addition to hundreds of new DNA methylation markers, our approach
      also identified markers that are in current clinical use, SEPT9 and GSTP1,
      indicating the validity of our approach and a significant potential utility for
      the newly discovered markers. The hypermethylated markers are linked to polycomb
      associated loci and a significant fraction of the discovered markers is within
      noncoding RNA genes; one of the best markers is MIR129-2. Future clinical testing
      of herein discovered markers will confirm new markers that will improve minimally
      invasive diagnosis and monitoring for multiple cancers.

PMID- 29212411
TI  - Geriatric Traumatic Brain Injury: Epidemiology, Outcomes, Knowledge Gaps, and
      Future Directions.
AB  - This review of the literature on traumatic brain injury (TBI) in older adults
      focuses on incident TBI sustained in older adulthood ("geriatric TBI") rather
      than on the separate, but related, topic of older adults with a history of
      earlier-life TBI. We describe the epidemiology of geriatric TBI, the impact of
      comorbidities and pre-injury function on TBI risk and outcomes, diagnostic
      testing, management issues, outcomes, and critical directions for future
      research. The highest incidence of TBI-related emergency department visits,
      hospitalizations, and deaths occur in older adults. Higher morbidity and
      mortality rates among older versus younger individuals with TBI may contribute to
      an assumption of futility about aggressive management of geriatric TBI. However,
      many older adults with TBI respond well to aggressive management and
      rehabilitation, suggesting that chronological age and TBI severity alone are
      inadequate prognostic markers. Yet there are few geriatric-specific TBI
      guidelines to assist with complex management decisions, and TBI prognostic models
      do not perform optimally in this population. Major barriers in management of
      geriatric TBI include under-representation of older adults in TBI research, lack
      of systematic measurement of pre-injury health that may be a better predictor of
      outcome and response to treatment than age and TBI severity alone, and lack of
      geriatric-specific TBI common data elements (CDEs). This review highlights the
      urgent need to develop more age-inclusive TBI research protocols, geriatric TBI
      CDEs, geriatric TBI prognostic models, and evidence-based geriatric TBI consensus
      management guidelines aimed at improving short- and long-term outcomes for the
      large and growing geriatric TBI population.

PMID- 29212415
TI  - Effects of cognitive remediation on cognitive and social functions in individuals
      with schizophrenia.
AB  - Individuals with schizophrenia exhibit cognitive impairments, which are related
      to impairments in social functions. This study investigated the effects of
      cognitive remediation on cognitive, social, and daily living impairment.
      Participants were individuals with schizophrenia between 20 and 60 years old (N =
      44). Participants were randomly assigned to two groups: a cognitive remediation
      intervention group and a non-intervention control group. The control group was
      provided with conventional drug therapy and either day care or occupational
      therapy. The intervention group was provided with the "neuropsychological
      educational approach to cognitive remediation" developed by Medalia and co
      workers. We assessed cognitive functions using the brief assessment of cognition
      in schizophrenia (BACS), and evaluated social and daily living functions using
      the global assessment of functioning (GAF) scale. Significant group by time
      interaction effects indicated that verbal memory, working memory, attention, and
      executive function showed significantly greater improvement at post-intervention
      for the intervention group than the control group. Social and daily living
      function also improved in the intervention group and improvements were maintained
      one year after intervention. These preliminary findings indicate that the
      combination of cognitive remediation and psychiatric rehabilitation is effective
      for facilitating improvements in cognitive function and social and daily living
      functions in individuals with schizophrenia.

PMID- 29212416
TI  - Pelvic venous reflux in male: Varicocele?

PMID- 29212417
TI  - Does the First Amendment Prevent or Allow FEMA to Provide Disaster Aid to
      Churches?

PMID- 29212418
TI  - Clinical characteristics and outcome of childhood acute promyelocitic leukemia
      (APL) in Saudi Arabia: a multicenter SAPHOS leukemia group study.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute
      myelogenous leukemia (AML). Survival rates exceed 80% in developed countries.
      Successful treatments rely on all-trans retinoic acid with anthracycline-based
      chemotherapy. Availability of modern care and public knowledge play important
      roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was
      confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo
      AML between January 2005 and December 2012 at nine cancer care centers in Saudi
      Arabia. Patients were treated based on the standard protocol used by the center
      following the PETHEMA or the C9710 treatment protocols. We modeled 5-year overall
      survival (OS), event-free survival (EFS) and cumulative incidence of relapse
      (CIR) vs. treatment and potential covariates of age at diagnosis, involvement of
      central nervous system (CNS), and white blood cell (WBC) levels. RESULTS: The
      median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 * 109/l or
      greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74
      +/- 12%, 55 +/- 19%, and, 36 +/- 17% respectively. No significant difference was
      found by treatment protocol. WBC levels were significantly prognostic for all
      negative events, but treatment with C9710 significantly ameliorated negative WBC
      effects. Overall outcomes were comparable to those reported in developed
      countries. CONCLUSIONS: Access to modern care is likely to be a critical factor
      in successful and comparable outcomes of childhood APL across the globe. In the
      present study, utilizing a cytarabine-containing protocol improved outcome of
      high-risk pediatric patients with APL.

PMID- 29212419
TI  - Surface modification of PHBV nanofiber mats for rapid cell cultivation and
      harvesting.
AB  - To maintain the original function of a specific tissue for therapeutic tissue
      engineering, an advanced cell culture surface for repeat cell proliferation is
      necessary. We designed a novel cell proliferation and rapid harvesting surface by
      combining nonwoven nanofiber mat and a thermo-responsive polymer. Nanofibrous
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) mats were fabricated by the
      electrospinning technique. A poly(N-isopropylacrylamide) (PNIPAM) thermo
      responsive layer was grafted on the PHBV nanofiber mat by electron beam
      irradiation. The average diameter of the PNIPAM-grafted PHBV nanofibers was
      determined by SEM. ATR-FTIR and ESCA were used to confirm the grafting of PNIPAM
      onto the PHBV nanofiber surface. Water contact angles on the mats were measured
      in response to temperature changes. Human adipose-derived stem cells (ADSCs) were
      cultured on the PNIPAM-grafted PHBV nanofiber mat to investigate cell
      proliferation, harvesting, and functionality during repeat subculture. Detached
      ADSCs from each surface by low temperature treatment and trypsin-EDTA were
      compared by a fluorescence-activated cell sorter (FACS) using expression of stem
      cell membrane-specific markers such as CD-13 PE, CD-29 PE, and CD-90 FITC. The
      mass cultivation and intact harvesting of stem cells by low temperature treatment
      using a thermo-responsive PHBV nanofiber mat is a promising technique for use in
      regenerative medicine and stem cell therapy.

PMID- 29212420
TI  - Durable response after VNCOP-B and rituximab in an elderly patient with high
      grade B-cell lymphoma.
AB  - OBJECTIVES AND METHODS:  High-grade B-cell lymphoma, NOS (HGBL) have an
      aggressive clinical behavior and poor outcome using regimens currently employed
      for diffuse large B-cell lymphoma (DLBCL) such as rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone (R-CHOP). Promising results have been
      reported with more intensive regimens but this strategy is not suitable for
      elderly or unfit patients. Rituximab in association with cyclophosphamide,
      mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (R-VNCOP-B)
      demonstrated high efficacy and manageable toxicity as first-line treatment for
      elderly aggressive non-Hodgkin lymphoma patients. RESULTS AND CONCLUSION: In this
      case study, we report the rapid improvement, long-lasting complete remission, and
      mild toxicity of R-VNCOP-B regimen in an elderly, triple-expressor HGBL patient,
      with aggressive disease and poor-risk profile.

PMID- 29212421
TI  - Antineoplastic chemotherapy in Jehovah's Witness patients with acute myelogenous
      leukemia refusing blood products - a matched pair analysis.
AB  - BACKGROUND: Acute myelogenous leukemia (AML) may be cured in a substantial number
      of patients using intensive chemotherapeutic regimens leading to temporary severe
      myelosuppression. Patients belonging to the denomination of Jehovah's Witnesses
      (JW), however, are bound by their religious convictions not to accept blood
      products and are therefore at higher risk for life-threatening events. Reports
      how to handle this challenge are mainly anecdotal. MATERIAL AND METHODS: We here
      report in much more detail about our experience with nine patients belonging to
      the denomination of JW who were treated for AML in our department from 1998 to
      2007 and who explicitly wished to receive chemotherapy without blood
      transfusions. RESULTS: Reduced dose induction chemotherapy administered by
      several treatment cycles to prevent sustained myelosuppression still led to
      complete remissions in three out of nine of JW patients but was associated with a
      high rate of relapse. No durable remission was achieved. The overall hazard ratio
      for death was 12.1 compared to a matched control group treated with full
      transfusion support. The predominant cause of non-AML mortality was severe anemia
      (four out of five early deaths) and uncontrollable bleeding (n = 1). CONCLUSION:
      Reduced dose chemotherapy without transfusion support in JW suffering from AML is
      associated with a lower rate of remission, high mortality by severe anemia and
      very low chances for long-term remissions. Less hematotoxic treatment options
      including hypomethylating agents or molecular targeted therapies with intensive
      consolidation after improvement of bone marrow function are promising for these
      patients but need further investigation.

PMID- 29212422
TI  - Growth curves of clients' emotional experience and their association with emotion
      regulation and symptoms.
AB  - OBJECTIVE: Emotional experience during psychotherapy is considered a core
      mechanism of change. Yet the sheer experience itself may not necessarily be
      beneficial; instead, the trajectories of emotional experience need to be explored
      as possible predictors of treatment outcomes. This study investigated whether
      clients' pre-treatment levels of emotion regulation and symptoms predicted
      patterns of session-to-session change in emotional experience. We also explored
      which patterns better predict clients' improvement in emotion regulation and
      symptoms from pre- to post treatment. METHOD: One-hundred and seven clients
      undergoing psychodynamic psychotherapy completed questionnaires on their symptoms
      and emotion regulation at pre- and post- treatment. They also reported their
      level of emotional experience at the end of each session. RESULTS: Pre-treatment
      symptoms and difficulties in emotion regulation predicted greater instability in
      emotional experience. Higher mean levels of emotional experience during treatment
      were associated with an improvement in emotion regulation, and greater stability
      during treatment was associated with improvement in emotion regulation and
      symptoms. CONCLUSIONS: These findings lend weight to the idea that experiencing
      emotion in the therapeutic environment has significant implications for clients'
      ability to manage their emotions outside the session. However, emotions
      experienced in an unstable manner within therapy are associated with poorer
      outcomes. Clinical and methodological significance of this article: Therapists
      can benefit from observing the patterns and not only the level of their clients'
      emotional experiences. The identification of clients' difficulties early in
      treatment may help therapists guide clients through the delicate process of
      carefully attending to their emotions.

PMID- 29212423
TI  - Subtraction computed tomography imaging to detect endoleaks after endovascular
      aneurysm sealing with sac anchoring.
AB  - Background Early detection of small type I endoleaks after endovascular aneurysm
      sealing is mandatory because they can rapidly progress and lead to severe
      complications. Recognition of endoleaks can be challenging due to the appearances
      on computed tomography unique to endovascular aneurysm sealing. We aimed to
      validate the accuracy and added value of subtraction computed tomography imaging
      using a post-processing software algorithm to improve detection of endovascular
      aneurysm sealing-associated endoleaks on postoperative surveillance imaging.
      Methods The computed tomography scans of 17 patients (16 males; median age: 78,
      range: 72-84) who underwent a post-endovascular aneurysm sealing computed
      tomography including both non-contrast and arterial phase series were used to
      validate the post processing software algorithm. Subtraction images are produced
      after segmentation and alignment. Initial alignment of the stent segmentations is
      automatically performed by registering the geometric centers of the 3D
      coordinates of both computed tomography series. Accurate alignment is then
      performed by translation with an iterative closest point algorithm. Accuracy of
      alignment was determined by calculating the root mean square error between
      matched 3D coordinates of stent segmentations. Results The median root mean
      square error after initial center of gravity alignment was 0.62 mm (IQR: 0.55
      0.80 mm), which improved to 0.53 mm (IQR: 0.47-0.69 mm) after the ICP alignment.
      Visual inspection showed good alignment and no manual adjustment was necessary.
      Conclusions The possible merit of subtraction computed tomography imaging for the
      detection of small endoleaks during surveillance after endovascular aneurysm
      sealing was illustrated. Alignment of different computed tomography phases using
      a software algorithm was very accurate. Further studies are needed to establish
      the exact role of this technique during surveillance after endovascular aneurysm
      sealing compared to less invasive techniques like contrast-enhanced ultrasound.

PMID- 29212424
TI  - Surgical complications of cochlear implantation in a tertiary university
      hospital.
AB  - INTRODUCTION: Cochlear implantation remains a popular and effective therapy for
      patients with sensorineural hearing loss that not get benefit from conventional
      hearing aids Objective: To analyze the surgical complications obtained in
      patients that underwent cochlear implantation in a tertiary university hospital.
      MATERIALS AND METHODS: Retrospective analysis of the medical files of cochlear
      implant patients who underwent surgery at our institution between October 2014
      and July 2016. This population comprised 163 patients (52.7% males and 47.3%
      females). Complications were classified in to 'major' and 'minor' complications
      depending on degree of management. RESULTS: Overall, the mean age at the time of
      implantation was 7.44 years. The cause of deafness was congenital in 81.6% of
      patients and acquired in 18.4% of patients. The overall complication rate was
      10.43%, 3.68% being major and 6.75% being minor complications. The most common
      minor complication in our series was wound complications, and the most common
      major complication was device failure. Excluding device failures, the major
      complication rate was 1.84%. CONCLUSION: Cochlear implantation is a safe surgical
      technique for rehabilitation of patients with severe to profound hearing loss,
      associated with a low surgical complications rate. The majority of surgical
      complications can be managed with conservative measures or minimal intervention.

PMID- 29212425
TI  - Sustainable recovery of valuable metals from spent lithium-ion batteries using DL
      malic acid: Leaching and kinetics aspect.
AB  - An eco-friendly and benign process has been investigated for the dissolution of
      Li, Co, Ni, and Mn from the cathode materials of spent LiNi1/3Co1/3Mn1/3O2
      batteries, using DL-malic acid as the leaching agent in this study. The leaching
      efficiencies of Li, Co, Ni, and Mn can reach about 98.9%, 94.3%, 95.1%, and
      96.4%, respectively, under the leaching conditions of DL-malic acid concentration
      of 1.2 M, hydrogen peroxide content of 1.5 vol.%, solid-to-liquid ratio of 40 g l
      1, leaching temperature of 80 degrees C, and leaching time of 30 min. In
      addition, the leaching kinetic was investigated based on the shrinking model and
      the results reveal that the leaching reaction is controlled by chemical reactions
      within 10 min with activation energies (Ea) of 21.3 kJ.mol-1, 30.4 kJ.mol-1, 27.9
      kJ.mol-1, and 26.2 kJ.mol-1 for Li, Co, Ni, and Mn, respectively. Diffusion
      process becomes the controlled step with a prolonged leaching time from 15 to 30
      min, and the activation energies (Ea) are 20.2 kJ.mol-1, 28.9 kJ.mol-1, 26.3
      kJ.mol-1, and 25.0 kJ.mol-1 for Li, Co, Ni, and Mn, respectively. This
      hydrometallurgical route was found to be effective and environmentally friendly
      for leaching metals from spent lithium batteries.

PMID- 29212426
TI  - Editor's Presentation.

PMID- 29212427
TI  - 2017 Year in Review.

PMID- 29212429
TI  - The impact of luteinizing hormone supplementation in gonadotropin-releasing
      hormone antagonist cycles: a retrospective cohort study.
AB  - The impact of exogenous luteinizing hormone (LH) supplementation to patients
      undergoing controlled ovarian stimulation with gonadotropin-releasing hormone
      (GnRH) antagonists on cycle outcomes is controversial. Here, we present a
      retrospective cohort study including cycles from December 2015 to December 2016.
      Totally 320 cycles were divided into two groups according to with or without
      exogenous LH supplementation. No significant differences regarding the number of
      retrieved oocytes, the number of good-quality embryos, and clinical pregnancy
      rate between the two groups were found. The logistic regression analysis revealed
      that LH supplementation was not independently associated with clinical pregnancy
      rate (OR = 0.577, 95% CI: 0.272-1.222, p = .58) or a biochemical pregnancy rate
      (OR = 0.922, 95% CI: 0.444-1.916, p = .83). When patients were divided into
      subgroups based on age, more retrieved oocytes (5.60 vs. 3.97, p = .04) and good
      quality embryos (3.07 vs. 1.93, p = .01) were achieved in cycles with exogenous
      LH supplementation for 40 years and over group. We conclude that for aged women
      (40 years old and over), LH supplementation has a positive impact on the number
      of retrieved oocytes and good-quality embryos in GnRH antagonist cycles.

PMID- 29212430
TI  - Work ability score and future work ability as predictors of register-based
      disability pension and long-term sickness absence: A three-year follow-up study.
AB  - AIMS: We investigated two single items of the Work Ability Index - work ability
      score, and future work ability - as predictors of register-based disability
      pension and long-term sickness absence over a three-year follow-up. METHODS:
      Survey responses of 11,131 Finnish employees were linked to pension and long-term
      (more than 10 days) sickness absence register data by Statistics Finland. Work
      ability score was divided into poor (0-5), moderate (6-7) and good/excellent (8
      10) and future work ability into poor (1-2) and good (3) work ability at
      baseline. Cox proportional hazard regressions were used in the analysis of
      disability pension, and a negative binomial model in the analysis of long-term
      sickness absence. The results were adjusted for several background, work- and
      health-related covariates. RESULTS: Compared with those with good/excellent work
      ability scores, the hazard ratios of disability pension after adjusting for all
      covariates were 9.84 (95% CI 6.68-14.49) for poor and 2.25 (CI 95% 1.51-3.35) for
      moderate work ability score. For future work ability, the hazard ratio was 8.19
      (95% CI 4.71-14.23) among those with poor future work ability. The incidence rate
      ratios of accumulated long-term sickness absence days were 3.08 (95% CI 2.19
      4.32) and 1.59 (95% CI 1.32-1.92) for poor and moderate work ability scores, and
      1.51 (95% CI 0.97-2.36) for poor future work ability. CONCLUSIONS: The single
      items of work ability score and future work ability predicted register-based
      disability pension equally well, but work ability score was a better predictor of
      register-based long-term sickness absence days than future work ability in a
      three-year follow-up. Both items seem to be of use especially when examining the
      risk of poor work ability for disability but also for long sick leave.

PMID- 29212431
TI  - A three-year national follow-up study on the development of community-level
      cancer rehabilitation in Denmark.
AB  - AIMS: Scandinavian cancer care policies emphasise community-level rehabilitation
      services, but little is known about changes in service provision over time. This
      follow-up study explores development in these services in Danish municipalities,
      focusing on availability, utilisation and organisation of services, including
      existing opportunities and challenges. METHODS: A national survey among all 98
      Danish municipalities was conducted in 2013 (baseline) and repeated in 2016
      (follow-up). The electronic questionnaire comprised closed- and open-ended
      questions. Data were analysed using descriptive statistics and content analysis.
      RESULTS: A total of 93 municipalities responded (95% response rate) and the
      services offered primarily comprised group physical activity, dietary advice,
      smoking cessation and individual counselling on physical activity. The number of
      patients enrolled was below the estimated number needing rehabilitation in
      Denmark. Inequality in utilisation by ethnicity, age and gender was reported. Key
      challenges for the delivery of services were: inadequate referral and recruitment
      procedures; lack of needs assessment tools; obstacles to ensuring collaboration
      and referral of patients between hospitals and municipalities; and inadequate
      evidence on the rehabilitation's effect. Key recommendations include ensuring
      collaboration between municipalities; provision of diagnosis-specific group-based
      activities; services focusing on physical activity; and gender-specific
      activities directed particularly at men. CONCLUSIONS: This study, which
      highlights improvements in the provision of community-level cancer
      rehabilitation, recommends that more effort be made to ensure equality in
      utilisation across patient groups, improved integration of municipal-level
      services into cancer care trajectories, more uniform documentation of service
      delivery and the enforcement of patient outcomes to gradually build a more robust
      evidence base for community-level cancer rehabilitation.

PMID- 29212432
TI  - Maternity leave duration and adverse pregnancy outcomes: An international country
      level comparison.
AB  - AIM: Preterm birth and low birthweight (LBW) lead to infant morbidity and
      mortality. The causes are unknown. This study evaluates the association between
      duration of maternity leave and birth outcomes at country level. METHOD: We
      compiled data on duration of maternity leave for 180 countries of which 36
      specified prenatal leave, 190 specified income, 183 specified preterm birth rates
      and 185 specified the LBW rate. Multivariate and seemingly unrelated regression
      analyses were done in STATA. RESULTS: Mean maternity leave duration was 15.4
      weeks ( SD=7.7; range 4-52 weeks). One additional week of maternity leave was
      associated with a 0.09% lower preterm rate (95% confidence interval [CI] -0.15 to
      -0.04) adjusting for income and being an African country. An additional week of
      maternity leave was associated with a 0.14% lower rate of LBW (95% CI -0.24 to 
      0.05). Mean prenatal maternity leave across 36 countries was six weeks ( SD=2.7;
      range 2-14 weeks). One week of prenatal maternity leave was associated with a
      0.07% lower preterm rate (95% CI -0.10 to 0.24) and a 0.06% lower rate of LBW
      (95% CI -0.14 to 0.27), but these results were not statistically significant. By
      adjusting for income status categories, the preterm birth rate was 1.53% higher
      and the LBW rate was 2.17% higher in Africa compared to the rest of the world.
      CONCLUSIONS: Maternity leave duration is significantly associated with birth
      outcomes. However, the association was not significant among 36 countries that
      specified prenatal maternity leave. Studies are needed to evaluate the
      correlation between prenatal leave and birth outcomes.

PMID- 29212433
TI  - Age Dependence of Thresholds for Speech in Noise in Normal-Hearing Adolescents.
AB  - Previously found effects of age on thresholds for speech reception thresholds in
      noise in adolescents as measured by an online screening survey require further
      study in a well-controlled teenage sample. Speech reception thresholds (SRT) of
      72 normal-hearing adolescent students were analyzed by means of the online speech
      in-noise screening tool Earcheck (In Dutch: Oorcheck). Screening was performed at
      school and included pure-tone audiometry to ensure normal-hearing thresholds. The
      students' ages ranged from 12 to 17 years. A group of young adults was included
      as a control group. Data were controlled for effects of gender and level of
      education. SRT scores within the controlled teenage sample revealed an effect of
      age on the order of an improvement of -0.2 dB per year. Effects of level of
      education and gender were not significant. Hearing screening tools that are based
      on SRT for speech in noise should control for an effect of age when assessing
      adolescents. Based on the present data, a correction factor of -0.2 dB per year
      between the ages of 12 and 17 is proposed. The proposed age-corrected SRT cut-off
      scores need to be evaluated in a larger sample including hearing-impaired
      adolescents.

PMID- 29212435
TI  - Adhesive capsulitis of the hip.
AB  - PURPOSE: Adhesive capsulitis of the hip (ACH) is not a well-defined disease
      entity. We evaluated the change in the clinical features of patients whose chief
      complaint was inability to sit cross-legged on the floor. All patients had
      painful limitation in hip joint motion. Based on the diagnosis of ACH, active
      stretching exercise (ASE) was recommended. METHODS: In February 2013 and June
      2014, a total of 44 patients (50 hips), who visited outpatient clinic in 2011,
      were evaluated by telephone interviews. Recovery of hip motion was analyzed
      according to compliance with ASE and abnormalities found on plane radiographs and
      magnetic resonance (MR) images. RESULTS: There were 27 women and 17 men with mean
      age of 51.7 years. In the first telephone interview, 40 patients (45 hips)
      reported improvement in hip motion but 4 patients (5 hips) reported absolutely no
      improvement. Compliance with ASE did not affect recovery of motion ( p = 0.225).
      On plain radiographs, 10 patients (22.7%) had abnormal finding in both hips.
      Those abnormal findings were not correlated with symptom and did not show adverse
      effect on motion recovery. Sixteen patients took MR images outside, and abnormal
      findings such as round ligament or labral tear were observed in nine patients.
      Those abnormal findings neither correlated with the symptom nor affected motion
      recovery adversely. In the second telephone interview, nine hips of further
      improvement and two hips of recurrence were identified. CONCLUSIONS: Most cases
      showed improvement in the range of motion with or without ASE. Surgical
      treatments including arthroscopy seemed to be unnecessary for these patients.

PMID- 29212434
TI  - Stable Isotope Pharmacokinetic Studies Provide Insight into Effects of Age, Sex,
      and Weight on Levothyroxine Metabolism.
AB  - BACKGROUND: This study sought to determine whether levothyroxine pharmacokinetics
      (PKs) are affected by age, weight, and sex. METHODS: A PK study was performed
      after administration of a tracer dose of carbon-13-labeled LT4 (13C-LT4). The
      study was conducted at an academic medical center. Adults of any age being
      treated with levothyroxine for hypothyroidism were enrolled in the study. A
      single dose of 13C-LT4 was administered. Eighteen serial plasma samples were
      collected. One sample was obtained before the 13C-LT4 dose, and the majority of
      the remaining samples were collected over the 120-hour period post dosing. 13C
      LT4 concentration was quantified using liquid chromatography tandem mass
      spectrometry. PK analysis was conducted using a linear log trapezoidal non
      compartmental analysis using Phoenix 6.4. RESULTS: Eight males and 33 females
      with a median age of 50 years (range 22-78 years) and median weight of 65.9 kg
      (range 50-150 kg) were enrolled in the study. The median 13C-LT4 dose
      administered was 100 MUg (range 70-300 MUg). The median oral clearance rate
      (CL/F), apparent volume of distribution (V/F), time to peak concentration (Tmax),
      and dose-normalized peak concentration (Cmax) of 13C-LT4 were estimated to be
      0.712 L/h, 164.9 L, 4 h, and 7.5 ng/L/MUg, respectively. The dose-normalized area
      under the concentration-time curve from time 0 to 120 hours and half-life of the
      terminal distribution phase were 0.931 ng.h/mL/MUg and 172.2 h, respectively.
      There was no significant difference in any 13C-LT4 PK parameter between patients
      aged >60 years (n = 10) and patients aged <=60 years (n = 31), nor was there a
      relationship between age as a continuous variable and 13C-LT4 PK parameters. Sex
      only affected CL/F, V/F, and dose-normalized Cmax in univariate analyses.
      However, after adjusting for weight, sex was no longer a significant covariate.
      Weight was a significant predictor for CL/F, V/F and dose-normalized Cmax of 13C
      LT4 in multivariate analyses. CONCLUSION: Prior studies suggest that patient age
      affects levothyroxine dose requirement. This study did not identify an effect of
      age and suggests that age-related changes in levothyroxine pharmacokinetics may
      be mediated by age-related weight differences. Physicians should consider a
      patient's weight, rather than age, for estimating levothyroxine dosage
      requirement.

PMID- 29212436
TI  - Estimation of individual thigh muscle volumes from a single-slice muscle cross
      sectional area and muscle thickness using magnetic resonance imaging in patients
      with knee osteoarthritis.
AB  - PURPOSE: This study aimed to identify the best single-slice anatomical muscle
      cross-sectional area (CSA) and muscle thickness (MT) on magnetic resonance
      imaging (MRI) to estimate the overall individual muscle volumes (MVs) of knee
      extensors and flexors in patients with knee osteoarthritis (KOA). METHODS: Twelve
      patients (24 legs; 4 men and 8 women) with KOA underwent a 1.5-Tesla axial MRI
      scan in the femoral region of interest (ROI), between the lesser trochanter and
      rectus femoris tendon. Individual MVs were calculated by numerical integration
      based on individual CSAs analyzed at the ROI. The best slice was determined as
      follows: coefficient of determination ( R2) between MVs measured and those
      estimated from the femoral length (FL) * CSAs or FL * MTs measured at each 10%
      interval level of the ROI. These estimation equations were applied for a cross
      validation group (24 KOA patients: 12 men and 12 women). RESULTS: Estimated
      individual MVs of knee extensors and flexors, based on the CSAs at the distal 10%
      level, significantly correlated with each of the measured individual MVs ( R2:
      0.79-0.96, p < 0.05 for all). Similarly, estimated individual knee extensor MVs,
      based on MTs at the mid-slice, significantly correlated with each of the measured
      individual MVs ( R2: 0.77-0.84, p < 0.05 for all). The application of the
      developed regression equation to the cross-validation group did not exhibit any
      systematic bias. CONCLUSION: These simple methods could be applied in prospective
      research with a larger number of patients with KOA.

PMID- 29212437
TI  - K-rod dynamic internal fixation versus microendoscopic discectomy for the
      treatment of single-segment lumbar disc herniation.
AB  - PURPOSE: This study compared the clinical outcome of K-rod dynamic internal
      fixation versus microendoscopic discectomy (MED) for the treatment of single
      segment lumbar disc herniation. METHODS: This retrospective study included 34
      patients with L4-L5 single-segment lumbar disc herniation who underwent K-rod
      dynamic internal fixation ( n = 18) or MED ( n = 16). The pain was evaluated by
      the Oswestry disability index (ODI) and visual analogue scale (VAS). The
      neurological function was assessed by the Japanese Orthopaedic Association (JOA)
      scores. The height of intervertebral space was calculated using X-ray images, and
      the disc degeneration was evaluated based on Pfirrmann scores. The mean follow-up
      time was 31 months (range, 18-46 months). RESULTS: In both groups, the ODI
      scores, VAS scores and JOA scores were significantly improved at the last follow
      up compared with the preoperative values ( p < 0.05). There was no significant
      difference in the improvement of ODI, VAS and JOA scores between the two groups (
      p > 0.05). The height of intervertebral space in the surgical segments, proximal
      segments and distal segments, was significantly greater in the K-rod group than
      in the MED group. The disc degeneration occurred more in the MED group than in
      the K-rod group ( p < 0.05). CONCLUSION: K-rod internal fixation and MED produce
      satisfactory outcomes in the treatment of single-segment lumbar disc herniation.
      K-rod internal fixation is superior to MED in preventing adjacent segment
      degeneration.

PMID- 29212439
TI  - Reversing Infertility After Chemotherapy.

PMID- 29212438
TI  - The Intensity and Timing of Sex Offender Treatment.
AB  - Current evidence about the impact of specialized sex offender treatment on
      reoffending remains inconsistent, drawing attention to the need to focus more on
      those program characteristics that potentially moderate outcome. This review
      considers current professional perspectives and evidence on two defining aspects
      of treatment: its intensity and timing. It is concluded that insufficient
      evidence currently exists to articulate best practice in this area and there is a
      pressing need to collect empirical evidence about the effectiveness of different
      intensity treatments offered at different stages of sentence.

PMID- 29212440
TI  - CONSTAX: a tool for improved taxonomic resolution of environmental fungal ITS
      sequences.
AB  - BACKGROUND: One of the most crucial steps in high-throughput sequence-based
      microbiome studies is the taxonomic assignment of sequences belonging to
      operational taxonomic units (OTUs). Without taxonomic classification, functional
      and biological information of microbial communities cannot be inferred or
      interpreted. The internal transcribed spacer (ITS) region of the ribosomal DNA is
      the conventional marker region for fungal community studies. While bioinformatics
      pipelines that cluster reads into OTUs have received much attention in the
      literature, less attention has been given to the taxonomic classification of
      these sequences, upon which biological inference is dependent. RESULTS: Here we
      compare how three common fungal OTU taxonomic assignment tools (RDP Classifier,
      UTAX, and SINTAX) handle ITS fungal sequence data. The classification power,
      defined as the proportion of assigned OTUs at a given taxonomic rank, varied
      among the classifiers. Classifiers were generally consistent (assignment of the
      same taxonomy to a given OTU) across datasets and ranks; a small number of OTUs
      were assigned unique classifications across programs. We developed CONSTAX
      (CONSensus TAXonomy), a Python tool that compares taxonomic classifications of
      the three programs and merges them into an improved consensus taxonomy. This tool
      also produces summary classification outputs that are useful for downstream
      analyses. CONCLUSIONS: Our results demonstrate that independent taxonomy
      assignment tools classify unique members of the fungal community, and greater
      classification power is realized by generating consensus taxonomy of available
      classifiers with CONSTAX.

PMID- 29212441
TI  - Evolution of cytokinesis-related protein localization during the emergence of
      multicellularity in volvocine green algae.
AB  - BACKGROUND: The volvocine lineage, containing unicellular Chlamydomonas
      reinhardtii and differentiated multicellular Volvox carteri, is a powerful model
      for comparative studies aiming at understanding emergence of multicellularity.
      Tetrabaena socialis is the simplest multicellular volvocine alga and belongs to
      the family Tetrabaenaceae that is sister to more complex multicellular volvocine
      families, Goniaceae and Volvocaceae. Thus, T. socialis is a key species to
      elucidate the initial steps in the evolution of multicellularity. In the asexual
      life cycle of C. reinhardtii and multicellular volvocine species, reproductive
      cells form daughter cells/colonies by multiple fission. In embryogenesis of the
      multicellular species, daughter protoplasts are connected to one another by
      cytoplasmic bridges formed by incomplete cytokinesis during multiple fission.
      These bridges are important for arranging the daughter protoplasts in appropriate
      positions such that species-specific integrated multicellular individuals are
      shaped. Detailed comparative studies of cytokinesis between unicellular and
      simple multicellular volvocine species will help to elucidate the emergence of
      multicellularity from the unicellular ancestor. However, the cytokinesis-related
      genes between closely related unicellular and multicellular species have not been
      subjected to a comparative analysis. RESULTS: Here we focused on dynamin-related
      protein 1 (DRP1), which is known for its role in cytokinesis in land plants.
      Immunofluorescence microscopy using an antibody against T. socialis DRP1 revealed
      that volvocine DRP1 was localized to division planes during cytokinesis in
      unicellular C. reinhardtii and two simple multicellular volvocine species T.
      socialis and Gonium pectorale. DRP1 signals were mainly observed in the newly
      formed division planes of unicellular C. reinhardtii during multiple fission,
      whereas in multicellular T. socialis and G. pectorale, DRP1 signals were observed
      in all division planes during embryogenesis. CONCLUSIONS: These results indicate
      that the molecular mechanisms of cytokinesis may be different in unicellular and
      multicellular volvocine algae. The localization of DRP1 during multiple fission
      might have been modified in the common ancestor of multicellular volvocine algae.
      This modification may have been essential for the re-orientation of cells and
      shaping colonies during the emergence of multicellularity in this lineage.

PMID- 29212442
TI  - Impact of inappropriate antifungal therapy according to current susceptibility
      breakpoints on Candida bloodstream infection mortality, a retrospective analysis.
AB  - BACKGROUND: The mortality of Candida Bloodstream Infection (CBSI) remains high.
      Antifungal susceptibility breakpoints were recently updated for Candida species,
      the impact remains unknown. In this study we evaluated the impact of
      inappropriate antifungal treatment according to recent breakpoints on 30-day
      mortality of CBSI. METHODS: From June 2008 to July 2014, data on CBSI episodes
      from two tertiary-care centers, treated > 72 h were analyzed. Antifungal therapy
      and 30-day mortality were registered. Inappropriate antifungal treatment
      according to current Clinical & Laboratory Standards Institute (CLSI) breakpoints
      was adjusted with 30-day mortality-related co-variates. RESULTS: One hundred
      forty-nine episodes of CBSI were analyzed. The most frequent species were: C.
      albicans (40%), C. tropicalis (23%) and C. glabrata complex (20%). According to
      the 2012 CLSI, 10.7% received inappropriate treatment. The 30-day mortality was
      38%; severe sepsis [Odds ratio (OR) 3.4; 95% CI 1.3-8.4], cirrhosis (OR 36; 95%
      CI 12.2-605), early central venous catheter removal (OR 0.23; 95% CI 0.08-0.66)
      and previous antifungal therapy (OR 0.15; 95%CI 0.03-0.62), were associated with
      30-day mortality by multivariate analysis. Inappropriate antifungal treatment was
      not (OR 0.19; 95% CI 0.03-1.2). CONCLUSIONS: Appropriate antifungal therapy
      according to CLSI 2012 did not have an impact on mortality. Mortality of CBSI
      remains high due to disease severity and comorbidities; early antifungal therapy
      and catheter removal may reduce it.

PMID- 29212443
TI  - The current incidence, prevalence, and residual risk of hepatitis B viral
      infections among voluntary blood donors in China.
AB  - BACKGROUND: There are few data available on the prevalence, incidence, and
      residual risk of transfusion-transmitted HBV (TT-HBV) infections among Chinese
      blood donors. This study investigated the demographic characteristics of blood
      donors, as well as the prevalence, incidence, and residual risk (RR) of TT-HBV
      infections in six large blood centers in different regions of China. METHODS: The
      demographic characteristics and HBV screening test results of blood donors from
      six blood centers in different regions in China were collected and analyzed. The
      hepatitis B surface antigen (HBsAg) yield approach was used to estimate the
      incidence of HBV. Then, the RR of TT-HBV infections was evaluated using the
      incidence-window period model. RESULTS: The majority of donors were between 18
      and 35 years old (including 35), with the exception of the Changzhi Blood Center
      where a majority of donors were between 35 and 55 years old (including 55). The
      prevalences of HBV were 0.13%, 0.078%, 0.16%, 0.07%, 0.20%, 0.25% in Hefei,
      Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. The estimated
      corresponding incidences were 213.44, 161.59, 989.80, 278.05, 125.31 and 352.19
      per 105 person-years. Using an infectious window period of 59 days, the RR for
      HBV was estimated to be 34.14, 25.85, 158.35, 44.48, 20.04 and 56.35 per 105
      person-years in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian,
      respectively. CONCLUSION: Despite the introduction of more sensitive assays in
      blood screening, our data revealed that the current residual risk of TT-HBV
      infection was still high (overall 56.53 per 105 py). A continuous monitoring of
      the residual risk of transfusion-transmitted infections is crucial for safe blood
      management.

PMID- 29212444
TI  - Multi-disciplinary team for early gastric cancer diagnosis improves the detection
      rate of early gastric cancer.
AB  - BACKGROUND: Gastric cancer is a frequent malignant tumor worldwide and its early
      detection is crucial for curing the disease and enhancing patients' survival
      rate. This study aimed to assess whether the multi-disciplinary team (MDT) can
      improve the detection rate of early gastric cancer (EGC). METHODS: The detection
      rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical
      College, China between September 2013 and September 2015 was analyzed. MDT for
      the diagnosis of EGC in the hospital was established in September 2014. The study
      was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1)
      and September 1, 2014 to September 1, 2015 (period 2). RESULTS: A total of 60,800
      patients' gastroscopies were performed during the two years. 61 of these patients
      (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients
      with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05%
      (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer
      during this period. In comparison, the EGC detection rate during MDT (period 2)
      was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric
      cancer during this period (P < 0.05). Univariate and multivariate logistic
      analyses showed that intensive gastroscopy for high risk patients of gastric
      cancer enhanced the detection rate of EGC in cooperation with Department of
      Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05). CONCLUSION: MDT could improve
      the endoscopic detection rate of EGC.

PMID- 29212445
TI  - Chromosome structures: reduction of certain problems with unequal gene content
      and gene paralogs to integer linear programming.
AB  - BACKGROUND: Chromosome structure is a very limited model of the genome including
      the information about its chromosomes such as their linear or circular
      organization, the order of genes on them, and the DNA strand encoding a gene.
      Gene lengths, nucleotide composition, and intergenic regions are ignored.
      Although highly incomplete, such structure can be used in many cases, e.g., to
      reconstruct phylogeny and evolutionary events, to identify gene synteny,
      regulatory elements and promoters (considering highly conserved elements), etc.
      Three problems are considered; all assume unequal gene content and the presence
      of gene paralogs. The distance problem is to determine the minimum number of
      operations required to transform one chromosome structure into another and the
      corresponding transformation itself including the identification of paralogs in
      two structures. We use the DCJ model which is one of the most studied
      combinatorial rearrangement models. Double-, sesqui-, and single-operations as
      well as deletion and insertion of a chromosome region are considered in the
      model; the single ones comprise cut and join. In the reconstruction problem, a
      phylogenetic tree with chromosome structures in the leaves is given. It is
      necessary to assign the structures to inner nodes of the tree to minimize the sum
      of distances between terminal structures of each edge and to identify the mutual
      paralogs in a fairly large set of structures. A linear algorithm is known for the
      distance problem without paralogs, while the presence of paralogs makes it NP
      hard. If paralogs are allowed but the insertion and deletion operations are
      missing (and special constraints are imposed), the reduction of the distance
      problem to integer linear programming is known. Apparently, the reconstruction
      problem is NP-hard even in the absence of paralogs. The problem of contigs is to
      find the optimal arrangements for each given set of contigs, which also includes
      the mutual identification of paralogs. RESULTS: We proved that these problems can
      be reduced to integer linear programming formulations, which allows an algorithm
      to redefine the problems to implement a very special case of the integer linear
      programming tool. The results were tested on synthetic and biological samples.
      CONCLUSIONS: Three well-known problems were reduced to a very special case of
      integer linear programming, which is a new method of their solutions. Integer
      linear programming is clearly among the main computational methods and, as
      generally accepted, is fast on average; in particular, computation systems
      specifically targeted at it are available. The challenges are to reduce the size
      of the corresponding integer linear programming formulations and to incorporate a
      more detailed biological concept in our model of the reconstruction.

PMID- 29212446
TI  - Transcriptomics analysis of the flowering regulatory genes involved in the
      herbicide resistance of Asia minor bluegrass (Polypogon fugax).
AB  - BACKGROUND: Asia minor bluegrass (Polypogon fugax, P. fugax), a weed that is both
      distributed across China and associated with winter crops, has evolved resistance
      to acetyl-CoA carboxylase (ACCase) herbicides, but the resistance mechanism
      remains unclear. The goal of this study was to analyze the transcriptome between
      resistant and sensitive populations of P. fugax at the flowering stage. RESULTS:
      Populations resistant and susceptible to clodinafop-propargyl showed distinct
      transcriptome profiles. A total of 206,041 unigenes were identified; 165,901
      unique sequences were annotated using BLASTX alignment databases. Among them,
      5904 unigenes were classified into 58 transcription factor families. Nine
      families were related to the regulation of plant growth and development and to
      stress responses. Twelve unigenes were differentially expressed between the
      clodinafop-propargyl-sensitive and clodinafop-propargyl-resistant populations at
      the early flowering stage; among those unigenes, three belonged to the ABI3VP1,
      BHLH, and GRAS families, while the remaining nine belonged to the MADS family.
      Compared with the clodinafop-propargyl-sensitive plants, the resistant plants
      exhibited different expression pattern of these 12 unigenes. CONCLUSION: This
      study identified differentially expressed unigenes related to ACCase-resistant P.
      fugax and thus provides a genomic resource for understanding the molecular basis
      of early flowering.

PMID- 29212447
TI  - On the impact of relatedness on SNP association analysis.
AB  - BACKGROUND: When testing for SNP (single nucleotide polymorphism) associations in
      related individuals, observations are not independent. Simple linear regression
      assuming independent normally distributed residuals results in an increased type
      I error and the power of the test is also affected in a more complicate manner.
      Inflation of type I error is often successfully corrected by genomic control.
      However, this reduces the power of the test when relatedness is of concern. In
      the present paper, we derive explicit formulae to investigate how heritability
      and strength of relatedness contribute to variance inflation of the effect
      estimate of the linear model. Further, we study the consequences of variance
      inflation on hypothesis testing and compare the results with those of genomic
      control correction. We apply the developed theory to the publicly available
      HapMap trio data (N=129), the Sorbs (a self-contained population with N=977
      characterised by a cryptic relatedness structure) and synthetic family studies
      with different sample sizes (ranging from N=129 to N=999) and different degrees
      of relatedness. RESULTS: We derive explicit and easily to apply approximation
      formulae to estimate the impact of relatedness on the variance of the effect
      estimate of the linear regression model. Variance inflation increases with
      increasing heritability. Relatedness structure also impacts the degree of
      variance inflation as shown for example family structures. Variance inflation is
      smallest for HapMap trios, followed by a synthetic family study corresponding to
      the trio data but with larger sample size than HapMap. Next strongest inflation
      is observed for the Sorbs, and finally, for a synthetic family study with a more
      extreme relatedness structure but with similar sample size as the Sorbs. Type I
      error increases rapidly with increasing inflation. However, for smaller
      significance levels, power increases with increasing inflation while the opposite
      holds for larger significance levels. When genomic control is applied, type I
      error is preserved while power decreases rapidly with increasing variance
      inflation. CONCLUSIONS: Stronger relatedness as well as higher heritability
      result in increased variance of the effect estimate of simple linear regression
      analysis. While type I error rates are generally inflated, the behaviour of power
      is more complex since power can be increased or reduced in dependence on
      relatedness and the heritability of the phenotype. Genomic control cannot be
      recommended to deal with inflation due to relatedness. Although it preserves type
      I error, the loss in power can be considerable. We provide a simple formula for
      estimating variance inflation given the relatedness structure and the
      heritability of a trait of interest. As a rule of thumb, variance inflation below
      1.05 does not require correction and simple linear regression analysis is still
      appropriate.

PMID- 29212448
TI  - From genomes to genotypes: molecular epidemiological analysis of Chlamydia
      gallinacea reveals a high level of genetic diversity for this newly emerging
      chlamydial pathogen.
AB  - BACKGROUND: Chlamydia (C.) gallinacea is a recently identified bacterium that
      mainly infects domestic chickens. Demonstration of C. gallinacea in human
      atypical pneumonia suggests its zoonotic potential. Its prevalence in chickens
      exceeds that of C. psittaci, but genetic and genomic research on C. gallinacea is
      still at the beginning. In this study, we conducted whole-genome sequencing of C.
      gallinacea strain JX-1 isolated from an asymptomatic chicken, and comparative
      genomic analysis between C. gallinacea strains and related chlamydial species.
      RESULTS: The genome of C. gallinacea JX-1 was sequenced by single-molecule, real
      time technology and is comprised of a 1,059,522-bp circular chromosome with an
      overall G + C content of 37.93% and sequence similarity of 99.4% to type strain
      08-1274/3. In addition, a plasmid designated pJX-1, almost identical to p1274 of
      the type strain, except for two point mutations, was only found in field strains
      from chicken, but not in other hosts. In contrast to chlamydial species with
      notably variable polymorphic membrane protein (pmp) genes and plasticity zone
      (PZ), these regions were conserved in both C. gallinacea strains. There were 15
      predicted pmp genes, but only B, A, E1, H, G1 and G2 were apparently intact in
      both strains. In comparison to chlamydial species where the PZ may be up to 50
      kbp, C. gallinacea strains displayed gene content reduction in the PZ (14 kbp),
      with strain JX-1 having a premature STOP codon in the cytotoxin (tox) gene, while
      tox gene is intact in the type strain. In multilocus sequence typing (MLST), 15
      C. gallinacea STs were identified among 25 strains based on cognate MLST allelic
      profiles of the concatenated sequences. The type strain and all Chinese strains
      belong to two distinct phylogenetic clades. Clade of the Chinese strains
      separated into 14 genetically distinct lineages, thus revealing considerable
      genetic diversity of C. gallinacea strains in China. CONCLUSIONS: In this first
      detailed comparative genomic analysis of C. gallinacea, we have provided evidence
      for substantial genetic diversity among C. gallinacea strains. How these genetic
      polymorphisms affect C. gallinacea biology and pathogenicity should be addressed
      in future studies that focus on phylogenetics and host adaption of this enigmatic
      bacterial agent.

PMID- 29212449
TI  - Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated
      with recurrent infertility in Japanese Black cattle.
AB  - BACKGROUND: Repeat breeding, which is defined as cattle failure to conceive after
      three or more inseminations in the absence of clinical abnormalities, is a
      substantial problem in cattle breeding. To identify maternal genetic variants of
      repeat breeding in Japanese Black cattle, we selected 29 repeat-breeding heifers
      that failed to conceive following embryo transfer (ET) and conducted a genome
      wide association study (GWAS) using the traits. RESULTS: We found that a single
      nucleotide polymorphism (SNP; g.92,377,635A > G) in the upstream region of the
      FOXP3 gene on the X chromosome was highly associated with repeat breeding and
      failure to conceive following ET (P = 1.51 * 10-14). FOXP3 is a master gene for
      differentiation of regulatory T (Treg) cells that function in pregnancy
      maintenance. Reporter assay results revealed that the activity of the FOXP3
      promoter was lower in reporter constructs with the risk-allele than in those with
      the non-risk-allele by approximately 0.68 fold. These findings suggest that the
      variant in the upstream region of FOXP3 with the risk-allele decreased FOXP3
      transcription, which in turn, could reduce the number of maternal Treg cells and
      lead to infertility. The frequency of the risk-allele in repeat-breeding heifers
      is more than that in cows, suggesting that the risk-allele could be associated
      with infertility in repeat-breeding heifers. CONCLUSIONS: This GWAS identified a
      maternal variant in the upstream region of FOXP3 that was associated with
      infertility in repeat-breeding Japanese Black cattle that failed to conceive
      using ET. The variant affected the level of FOXP3 mRNA expression. Thus, the
      results suggest that the risk-allele could serve as a useful marker to reduce and
      eliminate animals with inferior fertility in Japanese Black cattle.

PMID- 29212450
TI  - The impact of virus infections on pneumonia mortality is complex in adults: a
      prospective multicentre observational study.
AB  - BACKGROUND: Various viruses are known to be associated with pneumonia. However,
      the impact of viral infections on adult pneumonia mortality remains unclear. This
      study aimed to clarify the effect of virus infection on pneumonia mortality among
      adults stratified by virus type and patient comorbidities. METHODS: This
      multicentre prospective study enrolled pneumonia patients aged >=15 years from
      September 2011 to August 2014. Sputum samples were tested by in-house multiplex
      polymerase chain reaction assays to identify 13 respiratory viruses. Viral
      infection status and its effect on in-hospital mortality were examined by age
      group and comorbidity status. RESULTS: A total of 2617 patients were enrolled in
      the study and 77.8% was aged >=65 years. 574 (21.9%) did not have comorbidities,
      790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other
      comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus
      (9.8%) was the most frequently identified virus, followed by influenza A (3.9%)
      and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more
      frequently identified in patients with chronic respiratory disease (4.7%) than
      those with other comorbidities (4.2%) and without comorbidities (2.1%) (p =
      0.037). The frequencies of other viruses were almost identical between the three
      groups. Virus detection overall was not associated with increased mortality
      (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A
      and B were associated with three-fold higher mortality in patients with chronic
      respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54
      7.42). Intriguingly, paramyxoviruses were associated with dramatically lower
      mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but
      not with chronic respiratory disease. These effects were not affected by age
      group. CONCLUSIONS: The impact of virus infections on pneumonia mortality varies
      by virus type and comorbidity status in adults.

PMID- 29212451
TI  - A small pancreatic hamartoma with an obstruction of the main pancreatic duct and
      avid FDG uptake mimicking a malignant pancreatic tumor: a systematic case review.
AB  - BACKGROUND: Pancreatic hamartomas are extremely rare and may be misdiagnosed as
      malignant tumors. We report herein a case of a small, solid-type pancreatic
      hamartoma. CASE PRESENTATION: A 72-year-old female was incidentally detected
      pancreatic lesion by ultrasonography. Computed tomography and magnetic resonance
      imaging revealed a 2.0-cm solid lesion. The main pancreatic duct (MPD) was
      obstructed by the lesion in the head of the pancreas, and the upstream MPD was
      dilated. 18F-fluorodeoxyglucose (FDG) accumulated avidly in the lesion and
      increased in FDG intensity from the early to the delayed images. The
      histopathological studies confirmed the diagnosis of pancreatic hamartoma.
      Immunohistochemically, the cell membrane of the accessory glands and ducts showed
      homogeneous expression of glucose transporter type I and hexokinase II.
      CONCLUSION: Pancreatic hamartomas causing dilatation of the MPD are extremely
      rare, and this appears to be the first case of a hamartoma to take up FDG avidly.
      It was a rare occurrence and should be noted that pancreatic hamartomas can cause
      an obstruction of the MPD and show avid FDG uptake, thereby mimicking malignant
      pancreatic tumors.

PMID- 29212453
TI  - Mortality in persons with undetected and diagnosed hypertension, type 2 diabetes,
      and hypothyroidism, compared with persons without corresponding disease - a
      prospective cohort study; The HUNT Study, Norway.
AB  - BACKGROUND: Suggested strategies in reducing the impact of non-communicable
      diseases (NCD) are early diagnosing and screening. We have limited proof of
      benefit of population screening for NCD. Increased mortality in persons with
      diagnosed NCD has been shown for decades. However, mortality in undetected NCD
      has barely been studied. This paper explores whether all-cause mortality differed
      between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and
      hypertension, compared with persons with undetected-, and with persons without
      the corresponding disease. METHODS: A prospective cohort study of the general
      population in Nord-Trondelag, Norway. Persons >=20 years at baseline 1995-97 were
      followed until death or June 15, 2016. Cox proportional hazards models were used
      to compute age and multiple adjusted hazard ratios (HR) with 95% confidence
      intervals (CI) for the association between disease status and all-cause
      mortality. The number of participants in the hypothyroidism study was 31,960, in
      the T2DM study 37,957, and in the hypertension study 63,371. RESULTS: Mortality
      was increased in persons with diagnosed type 2 diabetes and hypertension,
      compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and
      HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the
      HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and
      hypertension, mortality was not increased compared with persons without the
      diseases. Further, the association with mortality was stronger in persons with
      long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95%
      CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53)
      and HR 1.16 (1.03-1-30) respectively). CONCLUSIONS: Mortality was increased in
      persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared
      with persons without the diseases. The strength of the association with mortality
      in undetected T2DM was however lower compared with persons with diagnosed T2DM,
      and mortality was not increased in persons with undetected hypothyroidism and
      hypertension, compared with persons without the diseases. Thus, future research
      needs to test more thoroughly if early diagnosing of these diseases, such as
      general population screening, is beneficial for health.

PMID- 29212452
TI  - The effectiveness of physiologically based early warning or track and trigger
      systems after triage in adult patients presenting to emergency departments: a
      systematic review.
AB  - BACKGROUND: Changes to physiological parameters precede deterioration of ill
      patients. Early warning and track and trigger systems (TTS) use routine
      physiological measurements with pre-specified thresholds to identify
      deteriorating patients and trigger appropriate and timely escalation of care.
      Patients presenting to the emergency department (ED) are undiagnosed,
      undifferentiated and of varying acuity, yet the effectiveness and cost
      effectiveness of using early warning systems and TTS in this setting is unclear.
      We aimed to systematically review the evidence on the use,
      development/validation, clinical effectiveness and cost-effectiveness of
      physiologically based early warning systems and TTS for the detection of
      deterioration in adult patients presenting to EDs. METHODS: We searched for any
      study design in scientific databases and grey literature resources up to March
      2016. Two reviewers independently screened results and conducted quality
      assessment. One reviewer extracted data with independent verification of 50% by a
      second reviewer. Only information available in English was included. Due to the
      heterogeneity of reporting across studies, results were synthesised narratively
      and in evidence tables. RESULTS: We identified 6397 citations of which 47 studies
      and 1 clinical trial registration were included. Although early warning systems
      are increasingly used in EDs, compliance varies. One non-randomised controlled
      trial found that using an early warning system in the ED may lead to a change in
      patient management but may not reduce adverse events; however, this is uncertain,
      considering the very low quality of evidence. Twenty-eight different early
      warning systems were developed/validated in 36 studies. There is relatively good
      evidence on the predictive ability of certain early warning systems on mortality
      and ICU/hospital admission. No health economic data were identified. CONCLUSIONS:
      Early warning systems seem to predict adverse outcomes in adult patients of
      varying acuity presenting to the ED but there is a lack of high quality
      comparative studies to examine the effect of using early warning systems on
      patient outcomes. Such studies should include health economics assessments.

PMID- 29212454
TI  - Ice age unfrozen: severe effect of the last interglacial, not glacial, climate
      change on East Asian avifauna.
AB  - BACKGROUND: The glacial-interglacial cycles in the Pleistocene caused repeated
      range expansion and contraction of species in several regions in the world.
      However, it remains uncertain whether such climate oscillations had similar
      impact on East Asian biota, despite its widely recognized importance in global
      biodiversity. Here we use both molecular and ecological niche profiles on 11 East
      Asian avian species with various elevational ranges to reveal their response to
      the late Pleistocene climate changes. RESULTS: The ecological niche models (ENM)
      consistently showed that these avian species might substantially contract their
      ranges to the south during the Last Interglacial period (LIG) and expanded their
      northern range margins through the Last Glacial Maximum (LGM), leading to the LGM
      ranges observed for all 11 species. Consistently, coalescent simulations based on
      25-30 nuclear genes retrieved signatures of significant population growth through
      the last glacial period across all species studied. Climate statistics suggested
      that high climatic variability during the LIG and a relatively mild climate at
      the LGM potentially explained the historical population dynamics of these birds.
      CONCLUSIONS: This is the first study based on multiple species and both lines of
      ecological niche profiles and genetic data to characterize the unique response of
      East Asian biota to late Pleistocene climate. The present study highlights
      regional differences in the evolutionary consequence of climate change during the
      last glacial cycle and implies that global warming might pose a great risk to
      species in this region given potentially higher climatic variation in the future
      analogous to that during the LIG.

PMID- 29212455
TI  - Comparative gene co-expression network analysis of epithelial to mesenchymal
      transition reveals lung cancer progression stages.
AB  - BACKGROUND: The epithelial to mesenchymal transition (EMT) plays a key role in
      lung cancer progression and drug resistance. The dynamics and stability of gene
      expression patterns as cancer cells transition from E to M at a systems level and
      relevance to patient outcomes are unknown. METHODS: Using comparative network and
      clustering analysis, we systematically analyzed time-series gene expression data
      from lung cancer cell lines H358 and A549 that were induced to undergo EMT. We
      also predicted the putative regulatory networks controlling EMT expression
      dynamics, especially for the EMT-dynamic genes and related these patterns to
      patient outcomes using data from TCGA. Example EMT hub regulatory genes were
      validated using RNAi. RESULTS: We identified several novel genes distinct from
      the static states of E or M that exhibited temporal expression patterns or
      'periods' during the EMT process that were shared in different lung cancer cell
      lines. For example, cell cycle and metabolic genes were found to be similarly
      down-regulated where immune-associated genes were up-regulated after middle EMT
      stages. The presence of EMT-dynamic gene expression patterns supports the
      presence of differential activation and repression timings at the transcriptional
      level for various pathways and functions during EMT that are not detected in pure
      E or M cells. Importantly, the cell line identified EMT-dynamic genes were found
      to be present in lung cancer patient tissues and associated with patient
      outcomes. CONCLUSIONS: Our study suggests that in vitro identified EMT-dynamic
      genes capture elements of gene EMT expression dynamics at the patient level.
      Measurement of EMT dynamic genes, as opposed to E or M only, is potentially
      useful in future efforts aimed at classifying patient's responses to treatments
      based on the EMT dynamics in the tissue.

PMID- 29212457
TI  - The decision delivery interval in emergency caesarean section and its associated
      maternal and fetal outcomes at a referral hospital in northern Tanzania: a cross
      sectional study.
AB  - BACKGROUND: Decision delivery interval (DDI) is the time line between a decision
      to conduct an emergency caesarean section and actual delivery of the baby.
      Prolong DDI constitute a third phase delay in provision of emergency obstetric
      care. Intervention designed to minimize DDI are vital, in attempt to prevent
      maternal morbidity and neonatal morbidity and mortality. The feasibility and
      practicability of the recommended DDI in recent studies have been questioned
      especially in limited resource setting and therefore the objective of our study
      was to determine the DDI and its associated fetalmaternal outcomes at a tertiary
      referral hospital in Tanzania. METHODS: This was a retrospectivecross-sectional
      study of inpatient cases who underwent emergency caesarean section from January
      to September 2014. Data were collected from birth registry and case files of
      patients. Data analysis was performed using statistical package for social
      science (SPSS) version 22.0. Odds ratio (ORs) and 95% confidence interval for
      maternal and fetal outcomes associated with DDI were estimated using Logistic
      regression models. A p-value of less than 5% was considered statistically
      significant. RESULTS: A total of 598 women who underwent emergency caesarean
      section were recruited. The median Decision Delivery Interval was 60 min [IQR 40
      120]. Only 12% were operated within 30 min from decision time. Shortest DDI was
      seen in patients with Cephalopelvic Disproportion (CPD) and uterine rupture (40
      min and 45.5 min) as compared to other conditions. Cases with impending uterine
      rupture, cord prolapse, APH and fetal distress showed to have shorter DDI. There
      was no significant association between DDI and neonatal transfer,1st and
      5thminute Apgar score, maternal blood loss (OR: 5.79; 95% CI 0.63-1.64) and
      hospital stay (OR: 1.02; 95% 0.63-1.64). CONCLUSIONS: Contrary to the recommended
      DDI by ACOG & AAP of 30 min is not feasible in our setting, time frame of 75 min
      could be acceptable but clinical judgment is required to assess on the urgency of
      caesarean section in order to prevent maternal and neonatal morbidity and
      mortality.

PMID- 29212456
TI  - Helicobacter-induced gastric inflammation alters the properties of gastric tissue
      stem/progenitor cells.
AB  - BACKGROUND: Although Helicobacter-induced gastric inflammation is the major
      predisposing factor for gastric carcinogenesis, the precise mechanism by which
      chronic gastritis causes gastric cancer remains unclear. Intestinal and
      spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as
      precancerous lesions, changes in epithelial tissue stem/progenitor cells after
      chronic inflammation has not been clarified yet. In this study, we utilized three
      dimensional gastric epithelial cell culture systems that could form organoids,
      mimicking gastric epithelial layer, and characterized the changes in epithelial
      cells after chronic Helicobacter felis infection. METHODS: We used three mice
      model; 1) long-term H. felis infection, 2) H. felis eradication, and 3) MNU
      chemical carcinogenesis model. We performed cRNA microarray analysis after
      organoid culture, and analyzed the effects of chronic gastric inflammation on
      tissue stem cells, by the size of organoid, mRNA expression profile and
      immunohistochemical analysis. RESULTS: The number of organoids cultured from
      gastric epithelial cells was significantly higher in organoids isolated from H.
      felis-infected mice compared with those from uninfected gastric mucosa. Based on
      the mRNA expression profile, we found that possible stem cell markers such as
      Cd44, Dclk1, and genes associated with the intestinal phenotype, such as Villin,
      were increased in organoids isolated from H. felis-infected mucosa compared with
      the control. The upregulation of these genes were cancelled after H. felis
      eradication. In a xenograft model, tumors were generated only from organoids
      cultured from carcinogen-treated gastric mucosa, not from H. felis infected
      mucosa or control organoids. CONCLUSIONS: Our results suggested that, as a
      possible mechanism of gastric carcinogenesis, chronic inflammation induced by H.
      felis infection increased the number of tissue stem/progenitor cells and the
      expression of stem cell markers. These findings suggest that chronic inflammation
      may alter the direction of differentiation toward undifferentiated state and that
      drawbacks may enable cells to redifferentiate to intestinal metaplasia or
      neoplasia.

PMID- 29212458
TI  - Associations of sedentary behavior and physical activity with older adults'
      physical function: an isotemporal substitution approach.
AB  - BACKGROUNDS: The purpose of this study was to examine, in a sample of Japanese
      older adults, the associations of objectively-assessed sedentary behavior (SB)
      and physical activity (PA) with performance-based physical function. The
      isotemporal substitution (IS) approach was used to model simultaneously the
      effects of the specific activity being performed and the activity being
      displaced, in an equal time-exchange manner. METHODS: Among 287 older adults (65
      84 years), we used accelerometers to identify the daily average time spent on SB
      (<=1.5 METs); light-intensity PA (LIPA) (>1.5 to <3.0 METs); and moderate- to
      vigorous-intensity PA (MVPA) (>=3.0 METs). Physical function was assessed using
      five performance-based measures: hand grip strength, usual and maximum gait
      speeds, timed up and go, and one-legged stance with eyes open. We employed three
      linear regression models - a single-activity model, a partition model, and an IS
      model - to assess the associations of SB, LIPA, and MVPA with each of the five
      measures of physical function. RESULTS: There were significant positive
      associations in the single-activity and partition models between MVPA and the
      measures of physical function (with the exception of hand grip strength). The IS
      models found that replacing SB or LIPA with MVPA was significantly and favorably
      associated with physical function measures. CONCLUSIONS: These findings indicate
      that replacing small amounts of SB and LIPA with MVPA (such as 10 min) may
      contribute to improvements in older adults' physical function.

PMID- 29212460
TI  - "The co-authors of pregnancy": leveraging men's sense of responsibility and other
      factors for male involvement in antenatal services in Kinshasa, DRC.
AB  - BACKGROUND: Despite efforts to improve male involvement (MI), few male partners
      typically attend antenatal care (ANC). MI in ANC and interventions to prevent
      mother-to-child HIV transmission have been demonstrated to be beneficial for the
      HIV-positive mother and her child. This study aimed to explore factors
      influencing partner attendance and highlight interventions with potential to
      improve MI within a Congolese context. METHODS: This was an exploratory,
      qualitative study conducted in two urban and two semi-urban catchment areas of
      Kinshasa, DRC in June-September 2016. Two women-only and two men-only focus group
      discussions (FGDs) were held; participants were recruited from ANC clinics and
      surrounding communities. Key informants purposively selected from health facility
      leadership and central government were also interviewed. Guide topics included MI
      barriers and facilitators, experiences with couples' ANC attendance and
      perceptions of MI interventions and how to improve them. Data from FGDs and
      interviews were analyzed to determine three interventions that best addressed the
      identified MI facilitators and barriers. These interventions were explored
      further through dialogues held with representatives from community organizations.
      RESULTS: This study included 17 female and 18 male FGD participants, 3 key
      informants and 21 community dialogue participants. Receipt of clinic staff advice
      was the most commonly-reported factor facilitating male attendance. No time off
      work was the most commonly-reported barrier. Only men identified responsibility,
      referring to themselves as "authors of the pregnancy," and wanting to be tested
      for HIV as facilitators. The most promising interventions perceived by FGD and
      interview participants were male partner invitation letters, couple- and male
      friendly improvements to ANC, and expert peer-to-peer outreach. Community
      dialogue participants provided further detail on these approaches, such as
      invitation letter content and counseling messages targeting men attending ANC.
      CONCLUSIONS: Common themes regarding male involvement in ANC that emerged from
      this study included men's need to understand how the pregnancy is progressing and
      how best to care for their female partners and unborn children, and ANC settings
      that were misaligned to the needs of men and couples. Interventions at the
      individual, facility and community levels were discussed that could result in
      improvements to male attendance at pregnancy-related services.

PMID- 29212459
TI  - Acquisition and persistence of strain-specific methicillin-resistant
      Staphylococcus aureus and their determinants in community nursing homes.
AB  - BACKGROUND: Nursing home residents are frequently colonized with various strains
      of methicillin-resistant Staphylococcus aureus (MRSA) but the intra-facility
      dynamics of strain-specific MRSA remains poorly understood. We aimed at
      identifying and quantifying the associations between acquisition and carriage of
      MRSA strains and their potential risk factors in community nursing homes using
      mathematical modeling. METHODS: The data was collected during a longitudinal MRSA
      surveillance study in six nursing homes in South Central Wisconsin. MRSA cultures
      were obtained from subjects every 3 months for up to one year. MRSA isolates were
      subsequently strain-typed by pulsed-field gel electrophoresis (PFGE), and their
      genetic similarity was established based on the Dice coefficients. Bayesian
      network analysis, logistic regression and elastic net were used to quantify the
      associations between acquisition and carriage of MRSA strains discriminated at
      80% and 95% strain similarity thresholds and potentially modifiable resident
      characteristics including previous antibiotic exposure, comorbidity, medical
      devices, chronic wounds, functional and cognitive status and recent
      hospitalizations. RESULTS: Absence of severe cognitive impairment as well as
      presence of a wound, device and severe comorbidity was associated with elevated
      probability of USA100 carriage although there was a variation based on the
      combination of those risk factors. Residents with severe comorbidity and
      cognitive status and presence of device and wound were identified as certain
      carriers of USA100 in our sample. Residents with a chronic wound were more likely
      to carry USA100 MRSA (OR = 2.77, 95% CI = 1.37-5.87). Functional status was
      identified as an important determinant of carriage of USA100 and USA300 strains.
      Comorbidity and cognitive status were the two factors associated with carriage of
      all clonal groups in the study (USA100, USA300 and USA1200). CONCLUSIONS: The
      combination of Bayesian network analysis, logistic regression and elastic net can
      be used to identify associations between acquisition and carriage of MRSA strains
      and their potential risk factors in the face of scarce data. The revealed
      associations may be used to generate hypothesis for further study of determinants
      of acquisition and carriage of selected MRSA subtypes and to better inform
      infection control efforts in community nursing homes.

PMID- 29212461
TI  - Widespread enlarged perivascular spaces associated with dementia and focal brain
      dysfunction: case report.
AB  - BACKGROUND: Enlarged perivascular spaces (PVS) are common magnetic resonance
      imaging (MRI) findings, whereas widespread enlarged PVS are extremely rare.
      Although most patients with widespread enlarged PVS remain asymptomatic, some
      develop neurological dysfunctions; however, it remains unclear whether these are
      the consequence of widespread enlarged PVS. CASE PRESENTATION: A 64-year-old
      female patient developed consciousness disturbance, cognitive dysfunctions,
      fluent aphasia, agraphia, acalculia, and left-right disorientation after
      suffering from bronchopneumonia. Brain MRI revealed unusually widespread enlarged
      PVS predominantly in the left cerebral hemisphere. Following bronchopneumonia
      treatment, her cognitive dysfunction, fluent aphasia, agraphia, acalculia, and
      left-right disorientation persisted despite improvement of her general condition.
      Furthermore, the hypoperfusion area on single photon emission computed tomography
      and slow wave sites on electroencephalography were consistent with the location
      of enlarged PVS, indicating that severe enlarged PVS impaired focal brain
      functions. CONCLUSIONS: This case suggested that widespread enlarged PVS could be
      a potential cause of neurological deficits. We propose that impaired perivascular
      circulation due to enlarged PVS might lead to focal brain dysfunction.

PMID- 29212462
TI  - Pharmacological targeting of secondary brain damage following ischemic or
      hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a
      systematic review and meta-analysis.
AB  - BACKGROUND: The effectiveness of pharmacological strategies exclusively targeting
      secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid
      hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI)
      and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD
      targeted treatment on clinical outcome across the pathological entities. METHODS:
      Randomized, controlled, double-blinded trials on aforementioned entities with
      'death' as endpoint were identified. Effect sizes were analyzed and expressed as
      pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies
      fulfilled the criteria, with data on 66,561 patients. RESULTS: In the pooled
      analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85
      1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95%
      CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05
      (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of
      "poor outcome" as endpoint gave similar results. Subgroup analysis with respect
      to effector mechanisms showed a tendency towards a reduced mortality for the
      effector mechanism category "oxidative metabolism/stress" for aSAH with a risk
      ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a
      statistically significant reduction of mortality and poor outcome was confirmed
      only for nimodipine for aSAH and dexamethasone for bacterial meningitis.
      CONCLUSIONS: Our results show that only a few selected SBD directed medications
      are likely to reduce the rate of death and poor outcome following aSAH, and
      bacterial meningitis, while no convincing evidence could be found for the
      usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However,
      a subtle effect on good or excellent outcome might remain undetected. These
      results should lead to a new perspective of secondary reactions following
      cerebral injury. These processes should not be seen as suicide mechanisms that
      need to be fought. They should be rather seen as well orchestrated clean-up
      mechanisms, which may today be somewhat too active in a few very specific
      constellations, such as meningitis under antibiotic treatment and aSAH after
      surgical or endovascular exclusion of the aneurysm.

PMID- 29212463
TI  - Could a remarkable decrease in leptin and insulin levels from colostrum to mature
      milk contribute to early growth catch-up of SGA infants?
AB  - BACKGROUND: Breast milk is known to contain many bioactive hormones and peptides,
      which can influence infant growth and development. In this context, the purpose
      of this study was to evaluate the influence of different clinical pregnancy
      conditions on hormone concentrations in colostrum and mature breast milk.
      METHODS: An observational study was performed with mother-newborn pairs divided
      into five groups according to maternal clinical background: diabetes (12),
      hypertension (5), smoking (19), intrauterine growth restriction of unknown causes
      with small-for-gestational-age newborns at delivery (12), and controls (21).
      Socioeconomic data, anthropometric measurements and breast milk samples were
      collected between the first 24 and 48 h and 30 days postpartum. Leptin,
      adiponectin, and insulin levels in breast milk were measured by immunoassays.
      RESULTS: A significant decrease in leptin (p = 0.050) and insulin (p = 0.012)
      levels from colostrum to mature breast milk in mothers of small-for-gestational
      age infants was observed. Maternal body mass index was correlated with both
      leptin and insulin, but not with adiponectin. Insulin levels were negatively
      correlated to infant weight gain from birth to one month (p = 0.050). In
      addition, catch-up growth was verified for small-for-gestational-age infants
      throughout the first month of life. CONCLUSIONS: This study suggests that a
      remarkable decrease in leptin and insulin levels in mature milk of mothers of
      small-for-gestational-age newborns may be involved in the rapid weight gain of
      these newborns. The physiological and external mechanisms by which these
      significant decreases and rapid weight gains occur in this group remain to be
      elucidated.

PMID- 29212464
TI  - Sexual dysfunction and mode of delivery in Chinese primiparous women: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Up to now, there is controversy over the effect of delivery mode
      cesarean delivery and spontaneous vaginal delivery on sexual function. Therefore,
      we did a systematic review and meta-analysis in postpartum women to explore the
      mode of delivery, cesarean delivery, and spontaneous vaginal delivery and
      differences in postpartum sexual function (short- and long-term) in Chinese
      primiparous women. METHODS: Comprehensive electronic searches of PubMed, EMBASE,
      Web of Science, Elsevier Science Direct, Cochrane Library, the Chinese Biological
      Medical Literature database and the Chinese National Knowledge Infrastructure
      database were conducted to identify any study in each database published to
      August 31, 2017. The primary outcome was the sexual satisfaction and the
      secondary outcomes were resumed intercourse and sexual pain in the postpartum.
      RESULTS: We identified 10 studies with a total population of 2851 in the present
      meta-analysis. Five and six eligible articles were respectively included for
      sexual satisfaction in postpartum at 3- and 6 months. Compared with vaginal
      delivery group, two time points were all not found statistically significance (OR
      1.53, 95%CI 0.93-2.49; OR 1.15, 95%CI 0.95-1.39, respectively) in cesarean and
      spontaneous vaginal delivery group; in resumed intercourse and sexual pain
      domains, they were all significantly, with an overall OR of 2.05 (95%CI 1.36
      3.11) at 3 months, 1.50 (95%CI 1.04-2.16) at 6 months and 0.29 (95%CI 0.24, 0.36)
      at 3 months, 0.73 (95%CI 0.58, 0.93) at 6 months, respectively. With the passage
      of time, the gap was closing. Sensitivity analysis was indicated a good stability
      of the meta-analysis in each domain. CONCLUSIONS: In conclusion, this meta
      analysis indicated that the mode of delivery, cesarean and spontaneous vaginal
      delivery did not affect postpartum sexual satisfaction (short- and long-term) and
      appeared to have minimal effect on the long-term resumed intercourse and sexual
      pain in Chinese primiparous women. Primiparous women should be more cautious to
      choose cesarean section in order to preserve sexual function.

PMID- 29212465
TI  - Association of 24 h-systolic blood pressure variability and cardiovascular
      disease in patients with obstructive sleep apnea.
AB  - BACKGROUND: To evaluate association of 24 h-systolic blood pressure (SBP)
      variability and obstructive sleep apnea (OSA) as defined by the apnea-hypopnea
      index >=5/h; and association of 24 h-SBP variability and prevalent cardiovascular
      disease (CVD) in OSA patients. METHODS: Participants underwent polysomongraphy to
      evaluate the presence of OSA, and 24 h-ambulatory blood pressure monitoring was
      applied to evaluate 24 h-SBP variability as indexed by weighted 24 h-standard
      deviation (SD) of SBP. Between-group differences were evaluated in participants
      with and without OSA. Participants with OSA were divided into high and low 24 h
      SBP variability groups and between-group differences were evaluated. RESULTS:
      Mean age of 384 participants was 50 years old and 42.2% had OSA. Mean 24 h
      systolic/diastolic BP were 130/78 mmHg, with mean weighted 24 h-SD of
      systolic/diastolic BP were 12.9/7.3 mmHg. Compared to those without OSA, OSA
      participants had higher clinic-, 24 h-, daytime- and nighttime-SBP, and weighted
      24 h, daytime- and nighttime-SD of SBP. Age, prevalent CVD and OSA, usage of
      angiotensin converting enzyme inhibitor/angiotensin receptor blocker, calcium
      channel blocker and diuretic were significantly associated with 24 h-SBP
      variability. In OSA patients, compared to those with low variability,
      participants with high variability had higher weighted 24 h, daytime- and
      nighttime-SD of SBP. After adjusted for covariates including clinic-SBP and 24 h
      SBP, per 1-SD increment weighted 24 h-SD of SBP was associated with 21% increased
      prevalent CVD. CONCLUSIONS: Patients with newly-diagnosed OSA have higher 24 h
      SBP variability compared to those without OSA; in OSA patients, increased 24 h
      SBP variability is associated with increased prevalence of CVD.

PMID- 29212466
TI  - Exploring the use of tablet computer-based electronic data capture system to
      assess patient reported measures among patients with chronic kidney disease: a
      pilot study.
AB  - BACKGROUND: Collecting patient reported outcome measures (PROMs) via computer
      based electronic data capture system may improve feasibility and facilitate
      implementation in clinical care. We report our initial experience about the
      acceptability of touch-screen tablet computer-based, self-administered
      questionnaires among patients with chronic kidney disease (CKD), including stage
      5 CKD treated with renal replacement therapies (RRT) (either dialysis or
      transplant). METHODS: We enrolled a convenience sample of patients with stage 4
      and 5 CKD (including patients on dialysis or after kidney transplant) in a single
      centre, cross-sectional pilot study. Participants completed validated
      questionnaires programmed on an electronic data capture system (DADOS, Techna
      Inc., Toronto) on tablet computers. The primary objective was to evaluate the
      acceptability and feasibility of using tablet-based electronic data capture in
      patients with CKD. Descriptive statistics, Fischer's exact test and multivariable
      logistic regression models were used for data analysis. RESULTS: One hundred and
      twenty one patients (55% male, mean age (+/- SD) of 58 (+/-14) years, 49%
      Caucasian) participated in the study. Ninety-two percent of the respondents
      indicated that the computer tablet was acceptable and 79% of the participants
      required no or minimal help for completing the questionnaires. Acceptance of
      tablets was lower among patients 70 years or older (75% vs. 95%; p = 0.011) and
      with little previous computer experience (81% vs. 96%; p = 0.05). Furthermore, a
      greater level of assistance was more frequently required by patients who were
      older (45% vs. 15%; p = 0.009), had lower level of education (33% vs. 14%; p =
      0.027), low health literacy (79% vs. 12%; p = 0.027), and little previous
      experience with computers (52% vs. 10%; p = 0.027). CONCLUSIONS: Tablet computer
      based electronic data capture to administer PROMs was acceptable and feasible for
      most respondents and could therefore be used to systematically assess PROMs among
      patients with CKD. Special consideration should focus on elderly patients with
      little previous computer experience, since they may require more assistance with
      completion.

PMID- 29212467
TI  - Excess pneumonia and influenza mortality attributable to seasonal influenza in
      subtropical Shanghai, China.
AB  - BACKGROUND: Disease burden attributable to influenza is substantial in
      subtropical regions. Our study aims to estimate excess pneumonia and influenza
      (P&I) mortality associated with influenza by subtypes/lineages in Shanghai,
      China, 2010-2015. METHODS: Quasi-Poisson regression models were fitted to weekly
      numbers of deaths from causes coded as P&I for Shanghai general and registered
      population. Three proxies for influenza activity were respectively used as an
      explanatory variable. Long-term trend, seasonal trend and absolute humidity were
      adjusted for as confounding factors. The outcome measurements of excess P&I
      mortality associated with influenza subtypes/lineages were derived by subtracting
      the baseline mortality from fitted mortality. RESULTS: Excess P&I mortality
      associated with influenza were 0.22, 0.30, and 0.23 per 100,000 population for
      three different proxies in Shanghai general population, lower than those in
      registered population (0.34, 0.48, and 0.36 per 100,000 population). Influenza B
      (Victoria) lineage did not contribute to excess P&I mortality (P = 0.206) while
      influenza B (Yamagata) lineage did (P = 0.044). Influenza-associated P&I
      mortality was high in the elderly population. CONCLUSIONS: Seasonal influenza A
      virus had a higher P&I mortality than influenza B virus, while B (Yamagata)
      lineage is the dominant lineage attributable to P&I mortality.

PMID- 29212468
TI  - A comparison of graph- and kernel-based -omics data integration algorithms for
      classifying complex traits.
AB  - BACKGROUND: High-throughput sequencing data are widely collected and analyzed in
      the study of complex diseases in quest of improving human health. Well-studied
      algorithms mostly deal with single data source, and cannot fully utilize the
      potential of these multi-omics data sources. In order to provide a holistic
      understanding of human health and diseases, it is necessary to integrate multiple
      data sources. Several algorithms have been proposed so far, however, a
      comprehensive comparison of data integration algorithms for classification of
      binary traits is currently lacking. RESULTS: In this paper, we focus on two
      common classes of integration algorithms, graph-based that depict relationships
      with subjects denoted by nodes and relationships denoted by edges, and kernel
      based that can generate a classifier in feature space. Our paper provides a
      comprehensive comparison of their performance in terms of various measurements of
      classification accuracy and computation time. Seven different integration
      algorithms, including graph-based semi-supervised learning, graph sharpening
      integration, composite association network, Bayesian network, semi-definite
      programming-support vector machine (SDP-SVM), relevance vector machine (RVM) and
      Ada-boost relevance vector machine are compared and evaluated with hypertension
      and two cancer data sets in our study. In general, kernel-based algorithms create
      more complex models and require longer computation time, but they tend to perform
      better than graph-based algorithms. The performance of graph-based algorithms has
      the advantage of being faster computationally. CONCLUSIONS: The empirical results
      demonstrate that composite association network, relevance vector machine, and Ada
      boost RVM are the better performers. We provide recommendations on how to choose
      an appropriate algorithm for integrating data from multiple sources.

PMID- 29212469
TI  - Orthogonal P-wave morphology is affected by intra-atrial pressures.
AB  - BACKGROUND: It has previously been shown that the morphology of the P-wave
      neither depends on atrial size in healthy subjects with physiologically enlarged
      atria nor on the physiological anatomical variation in transverse orientation of
      the left atrium. The present study aimed to investigate if different pressures in
      the left and right atrium are associated with different P-wave morphologies.
      METHODS: 38 patients with isolated, increased left atrial pressure, 51 patients
      with isolated, increased right atrial pressure and 76 patients with biatrially
      increased pressure were studied. All had undergone right heart catheterization
      and had 12-lead electrocardiographic recordings, which were transformed into
      vectorcardiograms for detailed P-wave morphology analysis. RESULTS: Normal P-wave
      morphology (type 1) was more common in patients with isolated increased pressure
      in the right atrium while abnormal P-wave morphology (type 2) was more common in
      the groups with increased left atrial pressure (P = 0.032). Moreover, patients
      with increased left atrial pressure, either isolated or in conjunction with
      increased right atrial pressure, had significantly more often a P-wave morphology
      with a positive deflection in the sagittal plane (P = 0.004). CONCLUSION:
      Isolated elevated right atrial pressure was associated with normal P-wave
      morphology while left-sided atrial pressure elevation, either isolated or in
      combination with right atrial pressure elevation, was associated with abnormal P
      wave morphology.

PMID- 29212470
TI  - Silencing of DND1 in potato and tomato impedes conidial germination, attachment
      and hyphal growth of Botrytis cinerea.
AB  - BACKGROUND: Botrytis cinerea, a necrotrophic pathogenic fungus, attacks many
      crops including potato and tomato. Major genes for complete resistance to B.
      cinerea are not known in plants, but a few quantitative trait loci have been
      described in tomato. Loss of function of particular susceptibility (S) genes
      appears to provide a new source of resistance to B. cinerea in Arabidopsis.
      RESULTS: In this study, orthologs of Arabidopsis S genes (DND1, DMR6, DMR1 and
      PMR4) were silenced by RNAi in potato and tomato (only for DND1). DND1 well
      silenced potato and tomato plants showed significantly reduced diameters of B.
      cinerea lesions as compared to control plants, at all-time points analysed.
      Reduced lesion diameter was also observed on leaves of DMR6 silenced potato
      plants but only at 3 days post inoculation (dpi). The DMR1 and PMR4 silenced
      potato transformants were as susceptible as the control cv Desiree. Microscopic
      analysis was performed to observe B. cinerea infection progress in DND1 well
      silenced potato and tomato leaves. A significantly lower number of B. cinerea
      conidia remained attached to the leaf surface of DND1 well-silenced potato and
      tomato plants and the hyphal growth of germlings was hampered. CONCLUSIONS: This
      is the first report of a cytological investigation of Botrytis development on
      DND1-silenced crop plants. Silencing of DND1 led to reduced susceptibility to
      Botrytis, which was associated with impediment of conidial germination and
      attachment as well as hyphal growth. Our results provide new insights regarding
      the use of S genes in resistance breeding.

PMID- 29212471
TI  - Investigation on the differentiation of two Ustilago esculenta strains -
      implications of a relationship with the host phenotypes appearing in the fields.
AB  - BACKGROUND: Ustilago esculenta, a pathogenic basidiomycete fungus, infects
      Zizania latifolia to form edible galls named Jiaobai in China. The distinct
      growth conditions of U. esculenta induced Z. latifolia to form three different
      phenotypes, named male Jiaobai, grey Jiaobai and white Jiaobai. The aim of this
      study is to characterize the genetic and morphological differences that
      distinguish the two U. esculenta strains. RESULTS: In this study, sexually
      compatible haploid sporidia UeT14/UeT55 from grey Jiaobai (T strains) and
      UeMT10/UeMT46 from white Jiaobai (MT strains) were isolated. Meanwhile, we
      successfully established mating and inoculation assays. Great differences were
      observed between the T and MT strains. First, the MT strains had a defect in
      development, including lower teliospore formation frequency and germination rate,
      a slower growth rate and a lower growth mass. Second, they differed in the
      assimilation of nitrogen sources in that the T strains preferred urea and the MT
      strains preferred arginine. In addition, the MT strains were more sensitive to
      external signals, including pH and oxidative stress. Third, the MT strains showed
      an infection defect, resulting in an endophytic life in the host. This was in
      accordance with multiple mutated pathogenic genes discovered in the MT strains by
      the non-synonymous mutation analysis of the genome re-sequencing data between the
      MT and T strains (GenBank accession numbers of the genome re-sequencing data:
      JTLW00000000 for MT strains and SRR5889164 for T strains). CONCLUSION: The MT
      strains appeared to have defects in growth and infection and were more sensitive
      to external signals compared to the T strains. They displayed an absolutely
      stable endophytic life in the host without an infection cycle. Accordingly, they
      had multiple gene mutations occurring, especially in pathogenicity. In contrast,
      the T strains, as phytopathogens, had a complete survival life cycle, in which
      the formation of teliospores is important for adaption and infection, leading to
      the appearance of the grey phenotype. Further studies elucidating the molecular
      differences between the U. esculenta strains causing differential host phenotypes
      will help to improve the production and formation of edible white galls.

PMID- 29212472
TI  - Autism risk classification using placental chorionic surface vascular network
      features.
AB  - BACKGROUND: Autism Spectrum Disorder (ASD) is one of the fastest-growing
      developmental disorders in the United States. It was hypothesized that variations
      in the placental chorionic surface vascular network (PCSVN) structure may reflect
      both the overall effects of genetic and environmentally regulated variations in
      branching morphogenesis within the conceptus and the fetus' vital organs. This
      paper provides sound evidences to support the study of ASD risks with PCSVN
      through a combination of feature-selection and classification algorithms.
      METHODS: Twenty eight arterial and 8 shape-based PCSVN attributes from a high
      risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas
      were examined for ranked relevance using a modified version of the random forest
      algorithm, called the Boruta method. Principal component analysis (PCA) was
      applied to isolate principal effects of arterial growth on the fetal surface of
      the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation
      was performed to establish error statistics. RESULTS: The Boruta method selected
      15 arterial attributes as relevant, implying the difference in high and low ASD
      risk can be explained by the arterial features alone. The five principal features
      obtained through PCA, which accounted for about 88% of the data variability,
      indicated that PCSVNs associated with placentas of high-risk ASD pregnancies
      generally had fewer branch points, thicker and less tortuous arteries, better
      extension to the surface boundary, and smaller branch angles than their
      population-based counterparts. CONCLUSION: We developed a set of methods to
      explain major PCSVN differences between placentas associated with high risk ASD
      pregnancies and those selected from the general population. The research paradigm
      presented can be generalized to study connections between PCSVN features and
      other maternal and fetal outcomes such as gestational diabetes and hypertension.

PMID- 29212473
TI  - Case report: bilateral Mooren ulcer in association with hepatitis C.
AB  - BACKGROUND: Mooren ulcer has been considered as an idiopathic autoimmune
      keratitis. However, it has been in some cases suggested to be associated with
      hepatitis C, although the evidence is very vague. CASE PRESENTATION: We present a
      case of a man who was diagnosed with a primary Mooren ulcer in his right eye. The
      eye became blind despite of intensive treatment with local medications and
      extensive surgical procedures. After 10 years, the patient was diagnosed with the
      same disease, now in his left, previously healthy eye. There was no history that
      would suggest a secondary Mooren ulcer, but a chronic hepatitis C infection was
      detected. Treatment was targeted against hepatitis C (ribavirin and interferon)
      in addition to immunosuppressive medical and surgical treatment which resulted in
      a full and more than 6 years lasting remission of the disease. CONCLUSIONS:
      Whether the immunomodulatory and immunosuppressive medication against hepatitis C
      was the key reason for the good results in the treatment of the second eye,
      remains elusive. The causality of hepatitis C with respect to the pathogenesis of
      Mooren ulcer on this patient remains open, but should be considered as one of the
      possible etiological factors of the disease.

PMID- 29212474
TI  - Coptis Chinensis affects the function of glioma cells through the down-regulation
      of phosphorylation of STAT3 by reducing HDAC3.
AB  - BACKGROUND: Glioma remains the most common cause of brain cancer-related
      mortality. Glioma accounts for 50-60% of brain cancer. Due to their low toxicity
      and infrequent side effects, traditional herbs have been increasingly popular.
      Coptis Chinensis is commonly used in cancer treatment in combination with other
      Chinese Medicine herbs. However, little is known about its biological functions
      and mechanisms in glioma cells. METHODS: In this study, the anti-glioma cell
      effect of Coptis Chinensis was determined using the 3-(4,5-dimethyl-2-thiazolyl)
      2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, plate clone test, scratch
      tests, flow cytometry, western blotting and a glioma xenograft tumor model.
      RESULTS: The results showed that Coptis Chinensis significantly suppressed glioma
      cell proliferation, tumor formation, migration and tumor growth, and prolonged
      the survival time of glioma cell-bearing mice. The flow cytometry result showed
      that Coptis Chinensis induced cell cycle arrest and apoptosis in glioma cells.
      Western blotting showed that Coptis Chinensis down-regulated the Signal
      transducer and activator of transcription 3 (STAT3) phosphorylation levels and
      reduced the expression of Histone deacetylase 3 (HDAC3) and caspase 3.
      CONCLUSIONS: Coptis Chinensis can inhibit various aspects of glioma cell
      functions. This study provides favorable scientific evidence for the potential
      use of natural products such as Coptis Chinensis in the clinical treatment of
      patients with glioma.

PMID- 29212475
TI  - Implementation of shared decision-making in oncology: development and pilot study
      of a nurse-led decision-coaching programme for women with ductal carcinoma in
      situ.
AB  - BACKGROUND: To implement informed shared decision-making (ISDM) in breast care
      centres, we developed and piloted an inter-professional complex intervention.
      METHODS: We developed an intervention consisting of three components: an evidence
      based patient decision aid (DA) for women with ductal carcinoma in situ, a
      decision-coaching led by specialised nurses (breast care nurses and oncology
      nurses) and structured physician encounters. In order to enable professionals to
      gain ISDM competencies, we developed and tested a curriculum-based training
      programme for specialised nurses and a workshop for physicians. After successful
      testing of the components, we conducted a pilot study to test the feasibility of
      the entire revised intervention in two breast care centres. Here the acceptance
      of the intervention by women and professionals, the applicability to the breast
      care centres' procedures, women's knowledge, patient involvement in treatment
      decision-making assessed with the MAPPIN'SDM-observer instrument MAPPIN'Odyad,
      and barriers to and facilitators of the implementation were taken into
      consideration. We used questionnaires, structured verbal and written feedback and
      video recordings. Qualitative data were analysed descriptively, and mean values
      and ranges of quantitative data were calculated. RESULTS: To test the DA, focus
      groups and individual interviews were conducted with 27 women. Six expert reviews
      were obtained. The components of the nurse training were tested with 18
      specialised nurses and 19 health science students. The development and piloting
      of the components were successful. The pilot test of the entire intervention
      included seven patients. In general, the intervention is applicable. Patients
      attained adequate knowledge (range of correct answers: 9-11 of 11). On average, a
      basic level of patient involvement in treatment decision-making was observed for
      nurses and patient-nurse dyads (M(MAPPIN-Odyad): 2.15 and M(MAPPIN-Onurse):
      1.90). Relevant barriers were identified; physicians barely tolerated women's
      preferences that were not in line with the medical recommendation. Classifying
      women as inappropriate for ISDM due to age or education led physicians to neglect
      eligible women during the recruitment phase. CONCLUSION: Decision-coaching is
      feasible. Nevertheless, there are some indications that structural changes are
      needed for long-term implementation. We are currently evaluating the intervention
      in a cluster randomised controlled trial in 16 breast care centres.

PMID- 29212476
TI  - The role of endoscopic ultrasound in children with Pancreatobiliary and
      gastrointestinal disorders: a single center series and review of the literature.
AB  - BACKGROUND: The role of endoscopic ultrasound (EUS) in the management of
      pancreatobiliary and digestive diseases is well established in adults, but it
      remains limited in children. The aim of this study was to evaluate the
      feasibility, safety, and clinical impact of EUS use in children. METHODS: This is
      a retrospective analysis of a prospectively acquired database of consecutive
      pediatric (< 18 years) patients presenting an indication for EUS for
      pancreatobiliary and gastrointestinal disorders. RESULTS: Between January 2010
      and January 2016, 47 procedures were performed in 40 children (mean age of 15.1
      +/- 4.7 years; range 3-18). The majority of EUS (n = 32; 68.1%) were performed
      for pancreatobiliary and upper gastrointestinal pathologies, including suspected
      common bile duct stones (CBDs), acute biliary pancreatitis, recurrent/chronic
      pancreatitis, cystic pancreatic mass, recurrent hypoglycemia, duodenal polyp,
      gastric submucosal lesion, and perigastric abscess. In only 2 out of 18 children
      with suspected CBDs or acute biliary pancreatitis, EUS confirmed CBDs. EUS-guided
      fine needle aspiration was performed in 3 (6.4%) patients. Fifteen (31.9%)
      procedures were performed for lower gastrointestinal tract disorders, including
      suspected anal Crohn's disease, fecal incontinence, and encopresis. Overall, EUS
      had a significant impact on the subsequent clinical management in 87.2% of
      patients. CONCLUSION: The present findings were consistent with results observed
      in the current relevant literature and support EUS as a safe and feasible
      diagnostic and therapeutic tool, which yields a significant clinical impact in
      children with pancreatobiliary and gastrointestinal disorders.

PMID- 29212477
TI  - Nurse health and lifestyle modification versus standard care in 40 to 70 year old
      regional adults: study protocol of the Management to Optimise Diabetes and
      mEtabolic syndrome Risk reduction via Nurse-led intervention (MODERN) randomized
      controlled trial.
AB  - BACKGROUND: Metabolic syndrome (MetS), the clustering of multiple leading risk
      factors, predisposes individuals to increased risk for developing type 2 diabetes
      and/or cardiovascular disease (CVD). Cardio-metabolic disease risk increases with
      greater remoteness where specialist services are scarce. Nurse-led interventions
      are effective for the management of chronic disease. The aim of this clinical
      trial is to determine whether a nurse-implemented health and lifestyle
      modification program is more beneficial than standard care to reduce cardio
      metabolic abnormalities and future risk of CVD and diabetes in individuals with
      MetS. METHODS: MODERN is a multi-centre, open, parallel group randomized
      controlled trial in regional Victoria, Australia. Participants were self-selected
      and individuals aged 40 to 70 years with MetS who had no evidence of CVD or other
      chronic disease were recruited. Those attending a screening visit with any 3 or
      more risk factors of central obesity, dyslipidemia (high triglycerides or low
      high density lipoprotein cholesterol) elevated blood pressure and dysglycemia
      were randomized to either nurse-led health and lifestyle modification
      (intervention) or standard care (control). The intervention included risk factor
      management, health education, care planning and scheduled follow-up commensurate
      with level of risk. The primary cardio-metabolic end-point was achievement of
      risk factor thresholds to eliminate MetS or minimal clinically meaningful changes
      for at least 3 risk factors that characterise MetS over 2 year follow-up. Pre
      specified secondary endpoints to evaluate between group variations in cardio
      metabolic risk, general health and lifestyle behaviours and new onset CVD and
      type 2 diabetes will be evaluated. Key outcomes will be measured at baseline, 12
      and 24 months via questionnaires, physical examinations, pathology and other
      diagnostic tests. Health economic analyses will be undertaken to establish the
      cost-effectiveness of the intervention. DISCUSSION: The MODERN trial will provide
      evidence for the potential benefit of independent nurse-run clinics in the
      community and their cost-effectiveness in adults with MetS. Findings will enable
      more nurse-led clinics to be adopted outside of major cities and encompassing
      other chronic diseases as a key primary preventative initiative. TRIAL
      REGISTRATION: MODERN is registered with the Australian New Zealand Clinical
      Trials Registry ( ACTRN12616000229471 ) on 19 February 2016 (retrospectively
      registered). Secondary identifiers: MODERN is an investigator-initiated trial
      funded by the National Health and Medical Research Council of Australia from 2014
      to 2017 via a Project Grant (ID No. APP1069043) and was approved by the
      Australian Catholic University Human Research Ethics Committee (Project No: 2014
      244 V) and the Department of Health Human Research Ethics Committee (Project
      No:38/2014) for the release of Medicare claims information.

PMID- 29212478
TI  - Effect of butorphanol, midazolam or ketamine on romifidine based sedation in
      horses during standing cheek tooth removal.
AB  - BACKGROUND: Standing surgery, especially dental procedures, are commonly
      performed in horses. This leads to an increasing demand for reliable sedation
      protocols. Therefore, it was the purpose of this study to investigate the
      influence of butorphanol, midazolam or ketamine on romifidine based sedation in
      horses during cheek tooth removal. METHODS: Forty horses presented for tooth
      extraction were divided in four groups using matched pair randomization. Group R
      was sedated with romifidine (bolus 0.03 mg/kg, followed by a constant rate
      infusion (CRI) 0.05 mg/kg/h) and group RB with romifidine (same dose) and
      butorphanol (0.02 mg/kg; CRI 0.04 mg/kg/h). Group RM received romifidine (same
      dose) and midazolam (0.02 mg/kg; CRI 0.06 mg/kg/h) whereas group RK was
      administered romifidine (same dose) and ketamine (0.5 mg/kg; CRI 1.2 mg/kg/h). If
      sedation was not adequate a top up bolus of romifidine (0.01 mg/kg) was
      administered. The quality of sedation and the conditions for tooth extraction,
      the level of ataxia, chewing, head and tongue movement were evaluated by using a
      scoring system. The investigator was blinded to the applied sedation protocol.
      Furthermore, serum cortisol concentrations before, during and after the procedure
      were analyzed to gain more information about the stress level of the horses.
      RESULTS: Horses in group RM showed significantly less chewing and tongue activity
      compared to horses sedated with romifidine alone or with butorphanol
      additionally, but also significantly higher levels of ataxia. The quality of
      sedation was significantly better if romifidine was administered in combination
      with ketamine compared to romifidine alone. Furthermore, horses of group RK
      needed less additional romifidine boli compared to all other groups. Blood
      cortisol concentrations during surgery in groups RB and RM remained unchanged.
      Horses of group R showed higher cortisol concentrations during sedation compared
      to horses of groups RB and RM. CONCLUSION: Romifidine alone at an initial bolus
      dose of 0.03 mg/kg followed by a constant rate infusion of 0.05 mg/kg/h was
      insufficient to obtain an adequate level of sedation and led to increased stress
      levels, whereas the addition of butorphanol inhibited the stress response. The
      combination of romifidine with either midazolam or ketamine improved sedation
      quality and surgical conditions.

PMID- 29212479
TI  - A pilot systematic genomic comparison of recurrence risks of hepatitis B virus
      associated hepatocellular carcinoma with low- and high-degree liver fibrosis.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection leads to liver fibrosis,
      which is a major risk factor in hepatocellular carcinoma (HCC) and an independent
      risk factor of recurrence after HCC tumor resection. The HBV genome can be
      inserted into the human genome, and chronic inflammation may trigger somatic
      mutations. However, how HBV integration and other genomic changes contribute to
      the risk of tumor recurrence with regards to the different degree of liver
      fibrosis is not clearly understood. METHODS: We sequenced mRNAs of 21 pairs of
      tumor and distant non-neoplastic liver tissues of HBV-HCC patients and performed
      comprehensive genomic analyses of our RNAseq data and public available HBV-HCC
      sequencing data. RESULTS: We developed a robust pipeline for sensitively
      identifying HBV integration sites based on sequencing data. Simulations showed
      that our method outperformed existing methods. Applying it to our data, 374 and
      106 HBV host genes were identified in non-neoplastic liver and tumor tissues,
      respectively. When applying it to other RNA sequencing datasets, consistently
      more HBV integrations were identified in non-neoplastic liver than in tumor
      tissues. HBV host genes identified in non-neoplastic liver samples significantly
      overlapped with known tumor suppressor genes. More significant enrichment of
      tumor suppressor genes was observed among HBV host genes identified from patients
      with tumor recurrence, indicating the potential risk of tumor recurrence driven
      by HBV integration in non-neoplastic liver tissues. We also compared SNPs of each
      sample with SNPs in a cancer census database and inferred samples' pathogenic SNP
      loads. Pathogenic SNP loads in non-neoplastic liver tissues were consistently
      higher than those in normal liver tissues. Additionally, HBV host genes
      identified in non-neoplastic liver tissues significantly overlapped with
      pathogenic somatic mutations, suggesting that HBV integration and somatic
      mutations targeting the same set of genes are important to tumorigenesis. HBV
      integrations and pathogenic mutations showed distinct patterns between low and
      high liver fibrosis patients with regards to tumor recurrence. CONCLUSIONS: The
      results suggest that HBV integrations and pathogenic SNPs in non-neoplastic
      tissues are important for tumorigenesis and different recurrence risk models are
      needed for patients with low and high degrees of liver fibrosis.

PMID- 29212480
TI  - The effect of nursing participation in the design of a critical care information
      system: a case study in a Chinese hospital.
AB  - BACKGROUND: Intensive care information systems (ICIS) are continuously evolving
      to meet the ever changing information needs of intensive care units (ICUs),
      providing the backbone for a safe, intelligent and efficient patient care
      environment. Although beneficial for the international advancement in building
      smart environments to transform ICU services, knowledge about the contemporary
      development of ICIS worldwide, their usage and impacts is limited. This study
      aimed to fill this knowledge gap by researching the development and
      implementation of an ICIS in a Chinese hospital, nurses' use of the system, and
      the impact of system use on critical care nursing processes and outcomes.
      METHODS: This descriptive case study was conducted in a 14-bed Respiratory ICU in
      a tertiary hospital in Beijing. Participative design was the method used for ICU
      nurses, hospital IT department and a software company to collaboratively research
      and develop the ICIS. Focus group discussions were conducted to understand the
      subjective perceptions of the nurses toward the ICIS. Nursing documentation time
      and quality were compared before and after system implementation. ICU nursing
      performance was extracted from the annual nursing performance data collected by
      the hospital. RESULTS: A participative design process was followed by the nurses
      in the ICU, the hospital IT staff and the software engineers in the company to
      develop and implement a highly useful ICIS. Nursing documentation was fully
      digitized and was significantly improved in quality and efficiency. The wrong
      data, missing data items and calculation errors were significantly reduced.
      Nurses spent more time on direct patient care after the introduction of the ICIS.
      The accuracy and efficiency of medication administration was also improved. The
      outcome was improvement in ward nursing performance as measured by ward
      management, routine nursing practices, disinfection and isolation, infection rate
      and mortality rate. CONCLUSIONS: Nurses in this ICU unit in China actively
      participated in the ICIS development and fully used the system to document care.
      Introduction of the ICIS led to significant improvement in quality and efficiency
      in nursing documentation, medication order transcription and administration. It
      allowed nurses to spend more time with patients to improve quality of care. These
      led to improvement in overall nursing performance. Further study should
      investigate how the ICIS system contributes to the improvement in decision making
      of ICU nurses and intensivists.

PMID- 29212481
TI  - Early anti-VEGF treatment for hemorrhagic occlusive retinal vasculitis as a
      complication of cataract surgery.
AB  - BACKGROUND: We report a case of hemorrhagic occlusive retinal vasculitis (HORV)
      after prophylactic intracameral vancomycin use during an uneventful cataract
      surgery treated with early anti-VEGF treatment. CASE PRESENTATION: A 51-year-old
      female underwent uneventful cataract surgery with prophylactic intracameral
      vancomycin during the procedure. On the seventh post-operative-day, she presented
      with sudden painful, visual loss. Fundus examination revealed peripheral
      hemorrhagic retinal vasculitis. She received anti-VEGF therapy to prevent further
      vision loss and retinal neovascularization due to extensive retinal ischemia. At
      the 6-month follow-up visit, visual acuity was 20/20 with no sign of
      neovascularization. CONCLUSIONS: Postoperative HORV is a devastating condition
      that can occur after otherwise uncomplicated cataract surgery. The nature of this
      rare condition remains unknown. Early anti-VEGF administration seems to
      demonstrate favorable results.

PMID- 29212482
TI  - Biosecurity aspects of cattle production in Western Uganda, and associations with
      seroprevalence of brucellosis, salmonellosis and bovine viral diarrhoea.
AB  - BACKGROUND: Many low-income countries have a human population with a high number
      of cattle owners depending on their livestock for food and income. Infectious
      diseases threaten the health and production of cattle, affecting both the farmers
      and their families as well as other actors in often informal value chains. Many
      infectious diseases can be prevented by good biosecurity. The objectives of this
      study were to describe herd management and biosecurity routines with potential
      impact on the prevalence of infectious diseases, and to estimate the burden of
      infectious diseases in Ugandan cattle herds, using the seroprevalence of three
      model infections. RESULTS: Farmer interviews (n = 144) showed that biosecurity
      measures are rarely practised. Visitors' hand-wash was used by 14%, cleaning of
      boots or feet by 4 and 79% put new cattle directly into the herd. During the 12
      months preceding the interviews, 51% of farmers had cattle that died and 31% had
      noticed abortions among their cows. Interestingly, 72% were satisfied with the
      health status of their cattle during the same time period. The prevalence (95%
      CI) of farms with at least one seropositive animal was 16.7% (11.0;23.8), 23.6%
      (16.9;31.4), and 53.4% (45.0;61.8) for brucella, salmonella and BVD,
      respectively. A poisson regression model suggested that having employees looking
      after the cattle, sharing pasture with other herds, and a higher number of dead
      cattle were associated with a herd being positive to an increasing number of the
      diseases. An additive bayesian network model with biosecurity variables and a
      variable for the number of diseases the herd was positive to resulted in three
      separate directed acyclic graphs which illustrate how herd characteristics can be
      grouped together. This model associated the smallest herd size with herds
      positive to a decreasing number of diseases and having fewer employees.
      CONCLUSION: There is potential for improvement of biosecurity practices in
      Ugandan cattle production. Salmonella, brucella and BVD were prevalent in cattle
      herds in the study area and these infections are, to some extent, associated with
      farm management practices.

PMID- 29212483
TI  - Fast food consumption and its associations with obesity and hypertension among
      children: results from the baseline data of the Childhood Obesity Study in China
      Mega-cities.
AB  - BACKGROUND: China has seen rapid increase in obesity and hypertension prevalence
      and fast food consumption over the past decade. We examined status and risk
      factors for Western- and Chinese fast food consumption and their associations
      with health outcomes in Chinese children, and examined how maternal factors were
      associated with child health outcomes. METHODS: Data of 1626 students aged 7-16
      (11.6 +/- 2.0) years and their parents in four mega-cities across China (Beijing,
      Shanghai, Nanjing, and Xi'an) were collected in the 2015 baseline survey of the
      Childhood Obesity Study in China Mega-cities. Weight, height, waist
      circumference, and blood pressure were measured. Food intake was assessed using
      questionnaire. Mixed models were used to examine the associations. RESULTS: Among
      the children, 11.1% were obese, 19.7% were centrally obese, and 9.0% had
      hypertension. Obesity prevalence was much higher in boys than in girls (15.2% vs.
      6.9% and 27.4% vs. 11.7%, respectively, both P < 0.001). About half (51.9% and
      43.6%) of children consumed Western and Chinese fast food, respectively, over the
      past 3 months. Compared to those with college or above maternal education level,
      those with elementary school or below maternal education level were 49% more
      likely to consume Western fast food (odds ratio [OR] and 95% confidence interval
      [CI]: 1.49 [1.10-2.03]). Chinese fast food consumption rate increased by 12% with
      each year of increase in child's age (OR and 95% CI: 1.12 [1.02-1.23]). No
      significant associations between fast food consumption and health outcomes were
      detected. Adjusting for Western fast food consumption, children with lower
      maternal education were 71% and 43% more likely to have obesity and central
      obesity (ORs and 95% CIs: 1.71 [1.12-2.61] and 1.43 [1.00-2.03], respectively),
      and maternal body mass index was positively associated with child obesity,
      central obesity, and hypertension (ORs and 95% CIs: 1.11 [1.06-1.17], 1.12 [1.07
      1.17], and 1.09 [1.03-1.15], respectively). Results were similar when Chinese
      fast food consumption was adjusted for. CONCLUSIONS: The prevalence of fast food
      consumption, obesity and hypertension is high among children in major cities in
      China. Maternal factors affect child outcomes.

PMID- 29212484
TI  - Clinical features of visual disturbances secondary to isolated sphenoid sinus
      inflammatory diseases.
AB  - BACKGROUND: Visual disturbances associated with isolated sphenoid sinus
      inflammatory diseases (ISSIDs) are easily misdiagnosed due to the nonspecific
      symptoms and undetectable anatomical location. The main objective of this
      retrospective case series is to investigate the clinical features of visual
      disturbances secondary to ISSIDs. METHODS: Clinical data of 23 patients with
      unilateral or bilateral visual disturbances secondary to ISSIDs from 2004 to 2014
      with new symptoms were collected. Collected data including symptoms, signs,
      neuroimaging and pathologic diagnosis were analyzed. RESULTS: There were 14 males
      and 9 females, and their ages ranged from 31 to 83 years. Fifteen patients
      suffered blurred vision and 11 patients suffered binocular double vision,
      including 3 patients who had unilateral visual changes and diplopia
      simultaneously. Headache was observed in 18 patients, and orbit pain/ocular pain
      in 8 patients. Other presenting symptoms included ptosis (4 patients) and
      proptosis (1 patient). Only 5 patients had nasal complaints. The corrected visual
      acuities were between NLP to 20/20. Patients with diplopia included 5 with
      unilateral oculomotor nerve palsy and 6 with unilateral abducens nerve palsy. All
      patients performed orbital/sinus/brain radiologic examination and found
      responsible lesions in sphenoid sinus. All patients underwent endoscopic sinus
      surgery, and 9 patients were found to suffer sphenoid mucocele, 9 with fungal
      sinusitis, and 5 with sphenoid sinusitis. Visual disturbances improved in 6
      patients, and all the patients with diplopia had a postoperative recovery.
      CONCLUSION: Visual disturbances resulting from ISSIDs are relatively uncommon,
      but it is crucial that the patient with new vision loss or diplopia and
      persistent headache or orbit pain be evaluated for the possibility of ISSIDs
      especially before corticosteroid administration.

PMID- 29212485
TI  - Outcome comparison between percutaneous cholecystostomy and cholecystectomy: a 10
      year population-based analysis.
AB  - BACKGROUND: Controversy surrounding the role of percutaneous cholecystostomy (PC)
      is fed by the absence of large amounts of data concerning its outcomes, and many
      authors have maintained that there is no evidence to support a recommendation for
      PC rather than cholecystectomy (CCS) in elderly or critically ill patients with
      acute cholecystitis (AC). METHODS: We conducted this study by tracking trends in
      the utilization and outcomes of PC and CCS using longitudinal health research
      data in Taiwan. RESULTS: Analyses were conducted on 236,742 patients, 11,184 of
      whom had undergone PC and 225,558 of whom had undergone CCS. Average annual
      percentage changes (AAPCs) from 2003 to 2012 increased significantly by 18.34%
      each year for PC and by 2.82% each year for CCS. The subset analyzes showed that
      the mortality rates were far higher in patients underwent PC than in patients
      underwent CCS in all subgroups, which increased from a minimum of 1.45-fold to a
      maximum of 34.22-fold. The gap of the mortality rates between PC group and CCS
      group narrowed as the patients aged and with the seriousness of the diseases
      increased. Most patients with PC or CCS who died in-hospital or within 30 days
      after discharge were 70 years of age or older, and a large number of them
      received a CCI score of at least 1. The AAPCs of the overall mortality rates from
      2003 to 2012 decreased by 6.78% each year for PC and by 7.33% each year for CCS.
      PC was related to a higher rate of cholecystitis recurrence and readmission for
      complications, but a lower rate of in-hospital complications and routine
      discharge than CCS, and 36.41% of all patients treated with PC underwent
      subsequent CCS. Additionally, the patients with PC experienced longer hospital
      stays and generated higher costs than the patients with CCS. CONCLUSION: Patients
      who underwent PC demonstrated poorer prognoses than did patients who underwent
      CCS. The role of PC in the Tokyo guidelines may be overstated; it is not as safe
      as the Tokyo guidelines have suggested in moderate-grade cholecystitis cases, and
      it should be limited to only the elderly and sicker patients.

PMID- 29212486
TI  - Emerging concepts and spectrum of renal injury following Intravesical BCG for non
      muscle invasive bladder cancer.
AB  - BACKGROUND: Intravesical Bacilli Calmette-Guerin (IVBCG) therapy for non-muscle
      invasive bladder cancer (NMIBC) has long been in use successfully. Albeit rarely,
      we still face with its safety concerns more than 25 years on since its approval
      by US Food and Drug Agency in 1990. Local and systemic infection following
      intravesical BCG is widely reported as compared to immune mediated local or
      systemic hypersensitivity reactions involving kidneys; acute kidney injury (AKI)
      and other renal manifestations are well reported but not of chronic kidney
      disease (CKD). CASE: An interesting case of a female was referred to
      nephrologists in advanced stages of CKD at an eGFR of 10 ml/min/1.732 following
      IVBCG for NMIBC. Our patient's renal function plateaued when IVBCG was held; and
      worsened again when reinstilled. It introduces the concept of 'repetitive' immune
      mediated renal injury presenting as progressive CKD rather than AKI, as is
      generally reported. Although response was poor, corticosteroids stopped CKD
      progression to end stage renal disease. CONCLUSIONS: We highlight the need for
      increased awareness and early recognition of IVBCG renal complications by both
      urologists and nephrologists in order to prevent progressive and irreversible
      renal damage. Low incidence of IVBCG renal complications may also be due to under
      recognition in the era prior to CKD Staging and AKI Network (and AKI e-alerts)
      that defined AKI as a rise in serum creatinine of >=26umol/L; hence an unmet need
      for urgent prospective studies. Major literature review focuses on emerging
      spectrum of histopathological IVBCG related renal complications and their
      outcomes.

PMID- 29212487
TI  - Recognizing difficult trade-offs: values and treatment preferences for end-of
      life care in a multi-site survey of adult patients in family practices.
AB  - BACKGROUND: Decisions about care options and the use of life-sustaining
      treatments should be informed by a person's values and treatment preferences. The
      objective of this study was to examine the consistency of ratings of the
      importance of the values statements and the association between values statement
      ratings and the patient's expressed treatment preference. METHODS: We conducted a
      multi-site survey in 20 family practices. Patients aged 50 and older self
      completed a questionnaire assessing the importance of eight values (rated 1 to
      10), and indicated their preference for use of life-sustaining treatment (5
      options). We compared correlations among values to a priori hypotheses based on
      whether the value related to prolonging or shortening life, and examined expected
      relationships between importance of values and the preference option for life
      sustaining treatment. RESULTS: Eight hundred ten patients participated (92%
      response rate). Of 24 a priori predicted correlations among values statements, 14
      were statistically significant but nearly all were negligible in their magnitude
      and some were in the opposite direction than expected. For example, the
      correlation between importance of being comfortable and suffering as little as
      possible and the importance of living as long as possible should have been
      inversely correlated but was positively correlated (r = 0.08, p = 0.03).
      Correlations between importance of values items and preference were negligible,
      ranging from 0.03 to 0.13. CONCLUSIONS: Patients may not recognize that trade
      offs in what is most important may be needed when considering the use of
      treatments. In the context of preparation for decision-making during serious
      illness, decision aids that highlight these trade-offs and connect values to
      preferences more directly may be more helpful than those that do not.

PMID- 29212488
TI  - Identification of the lipid biomarkers from plasma in idiopathic pulmonary
      fibrosis by Lipidomics.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial
      pulmonary disease featured by high mortality, chronic and progressive course, and
      poor prognosis with unclear etiology. Currently, more studies have been focusing
      on identifying biomarkers to predict the progression of IPF, such as genes,
      proteins, and lipids. Lipids comprise diverse classes of molecules and play a
      critical role in cellular energy storage, structure, and signaling. The role of
      lipids in respiratory diseases, including cystic fibrosis, asthma and chronic
      obstructive pulmonary disease (COPD) has been investigated intensely in the
      recent years. The human serum lipid profiles in IPF patients however, have not
      been thoroughly understood and it will be very helpful if there are available
      molecular biomarkers, which can be used to monitor the disease progression or
      provide prognostic information for IPF disease. METHODS: In this study, we
      performed the ultraperformance liquid chromatography coupled with quadrupole time
      of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and
      identify biomarker in plasma of IPF patients. The plasma were from 22 IPF
      patients before received treatment and 18 controls. RESULTS: A total of 507
      individual blood lipid species were determined with lipidomics from the 40 plasma
      samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types
      of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7
      types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By
      comparing the variations in the lipid metabolite levels in IPF patients, a total
      of 62 unique lipids were identified by statistical analysis including 24 kinds of
      glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds
      of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating
      lipids were selected as the potential biomarkers, which are able to differentiate
      between IPF disease and controls with ROC analysis. CONCLUSIONS: Our results
      provided vital information regarding lipid metabolism in IPF patients and more
      importantly, a few potentially promising biomarkers were firstly identified which
      may have a predictive role in monitoring and diagnosing IPF disease.

PMID- 29212489
TI  - Health-care utilization of patients with chronic back pain before and after
      rehabilitation.
AB  - BACKGROUND: Patients with chronic back pain show an increased use of health-care
      services leading to high direct costs. Multidisciplinary rehabilitation reduces
      pain intensity, depression, disability and work inability. The study aims to
      investigate whether health-care utilization in patients with chronic back pain is
      lower after rehabilitation than before rehabilitation and if, in addition to
      sociodemographic, medical and psychological characteristics, changes in these
      characteristics immediately after rehabilitation can predict health-care
      utilization. METHODS: N = 688 patients with chronic back pain were asked about
      their overall health-care services use and the use of general practitioners,
      specialists, physiotherapy, psychotherapy, complementary therapist, massages, and
      admission to hospital both 6 months before and 6 months after rehabilitation. In
      addition, various sociodemographic, medical and psychological variables were
      assessed. To measure changes due to rehabilitation, differences in pain
      intensity, disability, impairment and coping, quality of life, and days on sick
      leave before and after rehabilitation were calculated. Dependent t-tests and
      hierarchical regression analyses were used to analyse the data. RESULTS: Health
      care utilization 6 months after rehabilitation was, except for physiotherapy and
      psychotherapy, significantly lower than before. The effect sizes were rather
      small (Cohens'd =. 01-.34). After rehabilitation between 15.2% and 39.9% of the
      variance of health-care utilization could be explained. The baseline values of
      health-care utilization explained between 3.2% and 15.9% of the incremental
      variances. The changes in psychological impairment and coping as well as in sick
      leave after rehabilitation could explain between 0.8% and 2.9% of the variance of
      health-care utilization after rehabilitation. Its influence was significant for
      the general use of health-care services, general practitioners and specialists.
      CONCLUSIONS: The results indicate that use of health-care services after
      rehabilitation in the present study is slightly lower than before, which has an
      impact on direct costs due to chronic back pain in Germany. The predictors show
      the importance in terms of health-care utilization of improving work ability and
      psychological impairment.

PMID- 29212490
TI  - Attitudes towards assisted suicide and euthanasia among care-dependent older
      adults (50+) in Austria: the role of socio-demographics, religiosity, physical
      illness, psychological distress, and social isolation.
AB  - BACKGROUND: Care-dependency constitutes an important issue with regard to the
      approval of end-of-life decisions, yet attitudes towards assisted suicide and
      euthanasia are understudied among care-dependent older adults. We assessed
      attitudes towards assisted suicide and euthanasia and tested empirical
      correlates, including socio-demographics, religiosity, physical illness,
      psychological distress and social isolation. METHODS: A nationwide cross
      sectional survey among older care allowance recipients (50+) in private
      households in Austria was conducted in 2016. In computer-assisted personal
      interviews, 493 respondents were asked whether or not they approved of the
      availability of assisted suicide and euthanasia in case of long-term care
      dependency and whether or not they would consider using assisted suicide or
      euthanasia for themselves. Multiple logistic regression analysis was used to
      assess the impact of potential determinants of attitudes towards assisted suicide
      and euthanasia. RESULTS: About a quarter (24.8-26.0%) of the sampled care
      dependent older adults approved of the availability of assisted suicide and
      euthanasia respectively indicated the will to (hypothetically) make use of
      assisted suicide or euthanasia. Attitudes towards assisted suicide were most
      favourable among care-dependent older adults living in urban areas, those who did
      not trust physicians, those who reported active suicide ideation, and individuals
      with a strong fear of dying. With regard to euthanasia, living alone, religiosity
      and fear of dying were the central determinants of acceptance. CONCLUSIONS:
      Positive attitudes towards and will to (hypothetically) use assisted suicide and
      euthanasia were expressed by a substantial minority of care-dependent older
      adults in Austria and are driven by current psychological suffering and fear of
      the process of dying in the (near) future. Community-based psychosocial care
      should be expanded to address psychological distress and fears about end-of-life
      issues among care-dependent older adults.

PMID- 29212491
TI  - Case report: schwannoma arising from the unilateral adrenal area with bilateral
      hyperaldosteronism.
AB  - BACKGROUND: We report a rare case of a juxta-adrenal schwannoma that could not be
      discriminated from an adrenal tumor before surgical resection and was complicated
      by bilateral hyperaldosteronism. To the best of our knowledge, this is first case
      in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. CASE
      PRESENTATION: A 69-year-old male treated for hypertension was found to have a
      left supra-renal mass (5.8 * 5.2 cm) by abdominal computed tomography. His
      laboratory data showed that his plasma aldosterone concentration (PAC) was within
      the normal range, but his plasma renin activity (PRA) was reduced, resulting in
      an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide
      in the standing position demonstrated autonomous aldosterone secretion and renin
      suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated
      bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected
      because of the possibility of malignancy and was found to be a benign schwannoma
      arising from the juxta-adrenal region together with an adrenal gland. The
      dissected left adrenal gland was morphologically hyperplastic in the zona
      glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone
      synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in
      the adrenal gland, indicating micronodular hyperplasia. Although bilateral
      aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR
      values were within their respective reference ranges after resection of the
      unilateral tumor, suggesting that the slight increase in hormone secretion from
      the remaining right-sided lesion could not be detected after resection.
      CONCLUSION: A clinical and morphologic diagnosis of juxta-adrenal schwannoma is
      difficult, particularly in a case of hyperaldosteronism, as shown in this case.
      These data suggest the complexity and difficulty diagnosing adrenal
      incidentaloma.

PMID- 29212492
TI  - Using patient data to optimize an expert-based guideline on convalescence
      recommendations after gynecological surgery: a prospective cohort study.
AB  - BACKGROUND: Convalescence advice is often based on tradition and anecdote from
      health care providers, rather than being based on experiences from patients
      themselves. The aim of this study was to analyse recovery in terms of resumption
      of various daily activities including work, following different laparoscopic and
      abdominal surgery in order to optimize an expert-based guideline on convalescence
      recommendations. METHODS: This is a prospective cohort study conducted in nine
      general and one university hospital in the Netherlands. Women aged 18-65 years
      and scheduled for a hysterectomy (laparoscopic, vaginal, abdominal) and/or
      laparoscopic adnexal surgery (n = 304) were eligible to participate.
      Preoperatively, participants were provided with tailored expert-based
      convalescence recommendations on the graded resumption of several daily
      activities including sitting, standing, walking, climbing stairs, bending,
      lifting, driving, cycling, household chores, sport activities and return to work
      (RTW). Postoperatively, time until the resumption of these activities was
      tracked. Convalescence recommendations were considered correct when at least 25%
      and less than 50% of the women were able to resume an activity before or at the
      recommended recovery time. RESULTS: There was a wide variation in the duration
      until the resumption of daily activities within and between groups of patients
      undergoing different types of surgery. Recovery times lengthened with increasing
      levels of physical burden as well as with increasing levels of invasiveness of
      the surgery. For the majority of activities actual recovery times exceeded the
      recovery time recommended by the expert panel. CONCLUSIONS: This study provided
      insight in the resumption of daily activities after gynecological surgery and the
      adequacy of an expert-based convalescence guideline in clinical practice. Patient
      data was used to optimize the convalescence recommendations. TRIAL REGISTRATION:
      Dutch trial registry, NTR2087 (August 2009) and NTR2933 (June 2011).

PMID- 29212493
TI  - Development of a video-simulation instrument for assessing cognition in older
      adults.
AB  - BACKGROUND: Commonly used methods to assess cognition, such as direct
      observation, self-report, or neuropsychological testing, have significant
      limitations. Therefore, a novel tablet computer-based video simulation was
      created with the goal of being valid, reliable, and easy to administer. The
      design and implementation of the SIMBAC (Simulation-Based Assessment of
      Cognition) instrument is described in detail, as well as informatics "lessons
      learned" during development. RESULTS: The software emulates 5 common instrumental
      activities of daily living (IADLs) and scores participants' performance. The
      modules were chosen by a panel of geriatricians based on relevance to daily
      functioning and ability to be modeled electronically, and included facial
      recognition, pairing faces with the correct names, filling a pillbox, using an
      automated teller machine (ATM), and automatic renewal of a prescription using a
      telephone. Software development included three phases 1) a period of initial
      design and testing (alpha version), 2) pilot study with 10 cognitively normal and
      10 cognitively impaired adults over the age of 60 (beta version), and 3) larger
      validation study with 162 older adults of mixed cognitive status (release
      version). Results of the pilot study are discussed in the context of refining the
      instrument; full results of the validation study are reported in a separate
      article. In both studies, SIMBAC reliably differentiated controls from persons
      with cognitive impairment, and performance was highly correlated with Mini Mental
      Status Examination (MMSE) score. Several informatics challenges emerged during
      software development, which are broadly relevant to the design and use of
      electronic assessment tools. Solutions to these issues, such as protection of
      subject privacy and safeguarding against data loss, are discussed in depth.
      Collection of fine-grained data (highly detailed information such as time spent
      reading directions and the number of taps on screen) is also considered.
      CONCLUSIONS: SIMBAC provides clinicians direct insight into whether subjects can
      successfully perform selected cognitively intensive activities essential for
      independent living and advances the field of cognitive assessment. Insight gained
      from the development process could inform other researchers who seek to develop
      software tools in health care.

PMID- 29212494
TI  - Epidemiology and outcomes of children with renal failure in the pediatric ward of
      a tertiary hospital in Cameroon.
AB  - BACKGROUND: Pediatric nephrology is challenging in developing countries and data
      on the burden of kidney disease in children is difficult to estimate due to
      absence of renal registries. We aimed to describe the epidemiology and outcomes
      of children with renal failure in Cameroon. METHODS: We retrospectively reviewed
      103 medical records of children from 0 to 17 years with renal failure admitted in
      the Pediatric ward of the Douala General Hospital from 2004 to 2013. Renal
      failure referred to either acute kidney injury (AKI) or Stage 3-5 chronic kidney
      disease (CKD). AKI was defined and graded using either the modified RIFLE
      criteria or the Pediatrics RIFLE criteria, while CKD was graded using the KDIGO
      criteria. Outcomes of interest were need and access to dialysis and in-hospital
      mortality. For patients with AKI renal recovery was evaluated at 3 months.
      RESULTS: Median age was 84 months (1QR:15-144) with 62.1% males. Frequent
      clinical symptoms were asthenia, anorexia, 68.8% of participants had anuria. AKI
      accounted for 84.5% (n = 87) and CKD for 15.5% (n = 16). Chronic
      glomerulonephritis (9/16) and urologic malformations (7/16) were the causes of
      CKD and 81.3% were at stage 5. In the AKI subgroup, 86.2% were in stage F, with
      acute tubular necrosis (n = 50) and pre-renal AKI (n = 31) being the most
      frequent mechanisms. Sepsis, severe malaria, hypovolemia and herbal concoction
      were the main etiologies. Eight of 14 (57%) patients with CKD, and 27 of 40
      (67.5%) with AKI who required dialysis, accessed it. In-hospital mortality was
      50.7% for AKI and 50% for CKD. Of the 25 patients in the AKI group with available
      data at 3 months, renal recovery was complete in 22, partial in one and 2 were
      dialysis dependent. Factors associated to mortality were young age (p = 0.001),
      presence of a coma (p = 0.021), use of herbal concoction (p = 0.024) and acute
      pulmonary edema (p = 0.011). CONCLUSION: Renal failure is severe and carries a
      high mortality in hospitalized children in Cameroon. Limited access to dialysis
      and lack of specialized paediatric nephrology services may explain this dismal
      picture.

PMID- 29212495
TI  - Feasibility of tissue re-biopsy in non-small cell lung cancers resistant to
      previous epidermal growth factor receptor tyrosine kinase inhibitor therapies.
AB  - BACKGROUND: When epidermal growth factor receptor (EGFR) gene mutation-positive
      non-small cell lung cancer (NSCLC) acquires resistance to the initial tyrosine
      kinase inhibitor (TKI) treatment, reassessing the tumor DNA by re-biopsy is
      essential for further treatment selection. However, the process of TKI-sensitive
      tumor re-progression and whether re-biopsy is possible in all cases of acquired
      resistance to EGFR-TKI remain unclear. METHODS: We retrospectively analyzed data
      from 69 consecutive patients with EGFR gene mutation-positive advanced NSCLC who
      had been treated with EGFR-TKI and exhibited disease relapse after initial
      disease remission. The relapsing lesions were identified at the time of RECIST
      progressive disease (PD) and clinical-PD (when the attending physician judged the
      patient as clinically relapsing and stopped EGFR-TKI therapy). We determined the
      potential re-biopsy methods for each relapsing lesion and evaluated their
      feasibility according to difficulty and invasiveness criteria as follows:
      category A, accessible by conventional biopsy techniques; category B, difficult
      (but possible) to biopsy and accessible with invasive methods; and category C,
      extremely difficult to biopsy or inaccessible without using highly invasive
      methods, including surgical biopsy. RESULTS: The total feasibility rate of re
      biopsy (category A or B) was 68% at RECIST-PD and 84% at clinical-PD, and the
      most common accessible relapsing lesions were primary tumors at RECIST-PD and
      pleural effusion at clinical-PD. All relapsing lesions at primary sites
      (categories A and B) were assessed as having the potential for re-biopsy.
      However, re-biopsy for metastasis was assessed as difficult in a substantial
      proportion of the study population (42 and 20% category C at RECIST-PD and
      clinical-PD, respectively). CONCLUSIONS: Re-biopsy of relapsing disease is
      feasible in many cases, although it may present difficulties in cases with, e.g.,
      metastatic relapsing lesions. To facilitate treatment strategies in NSCLC
      patients with relapse after EGFR-TKI therapy, re-biopsy should be standardized
      with the use of simpler and more reliable methods.

PMID- 29212496
TI  - Pulmonary function, exhaled nitric oxide and symptoms in asthma patients with
      obesity: a cross-sectional study.
AB  - BACKGROUND: Obesity is a risk factor for the development of asthma. In patients
      with obesity the diagnosis of asthma is often based on symptoms, but without
      objective measurements. Nevertheless, obesity-associated asthma is recognized as
      a distinct asthma phenotype. Therefore, this study explores lung function and
      symptoms in asthma patients with and without obesity. METHODS: The Netherlands
      Epidemiology of Obesity (NEO) study is a population-based cohort study with 6671
      participants (aged 45-65 years) of whom 472 had asthma. Of this latter group,
      linear regression analysis was used to examine differences in lung function and
      symptoms between asthma patients with (n = 248) and without obesity (n = 224),
      and between asthma patients with and without increased FeNO. Analyses were
      adjusted for confounders. RESULTS: Asthma patients with obesity had lower
      predicted FEV1 and FVC values than patients without obesity [adjusted mean
      difference (MD) -3.3% predicted, 95% CI -6.5, -0.2; adjusted MD -5.0% predicted,
      95% CI -7.8, -2.1]. The prevalence of symptoms was higher in patients with
      obesity. Asthma patients with obesity and with increased FeNO had lower FEV1 and
      FEV1/FVC values compared with those with low FeNO (adjusted MD -6.9% predicted,
      95% CI -11.7, -2.0; -2.4%, 95% CI -4.6, -0.2). CONCLUSION: Asthma patients with
      obesity had lower FEV1 and FVC values than patients without obesity. This
      suggests that patients with obesity have restrictive lung function changes,
      rather than obstructive changes. Asthma patients with obesity and increased FeNO
      showed more obstructive changes. FeNO might help to identify patients with
      eosinophilic inflammation-driven asthma, whereas patients with low FeNO might
      have an obesity-associated asthma phenotype in which symptoms are partly caused
      by the obesity.

PMID- 29212497
TI  - Adverse events recording in electronic health record systems in primary care.
AB  - BACKGROUND: Adequate record keeping of medication adverse events in electronic
      health records systems is important for patient safety. Events that remain
      unrecorded cannot be communicated from one health professional to another. In the
      absence of a gold standard, we investigate the variation between Dutch general
      practices in the extent to which they record medication adverse events. METHODS:
      Data were derived from electronic health records (EHR) of Dutch general practices
      participating in NIVEL Primary Care Database (NIVEL-PCD) in 2014, including 308
      general practices with a total practice population of 1,256,049 listed patients.
      Medication adverse events were defined as recorded ICPC-code A85 (adverse effect
      medical agent). Between practice variation was studied using multilevel logistic
      regression analysis corrected for age, gender, number of different medicines
      prescriptions and number of chronic diseases. RESULTS: In 2014 there were 8330
      patients with at least one medication adverse event recorded. This corresponds to
      6.9 medication adverse events per 1000 patients and is higher for women, elderly,
      patients with polypharmacy and for patients with comorbidity. Corrected for these
      patient characteristics the median odds ratio (MOR = 1.92) suggests an almost
      twofold difference between general practices in recorded medication adverse
      events. CONCLUSION: Our results suggest that improvement in terms of uniformity
      in recording medication adverse events is possible, preventing potential damage
      for patients. We suggest that creating a learning health system by individual
      practice feedback on the number of recordings of adverse events would help
      practitioners to improve their recording habits.

PMID- 29212498
TI  - Salvianolic acid B protects against lipopolysaccharide-induced behavioral
      deficits and neuroinflammatory response: involvement of autophagy and NLRP3
      inflammasome.
AB  - BACKGROUND: The NLRP3 inflammasome activation and neuroinflammation are known to
      be involved in the pathology of depression, whereas autophagy has multiple
      effects on immunity, which is partly mediated by the regulation of inflammasome
      and clearance of proinflammatory cytokines. Given the emerging evidence that
      autophagy dysfunction plays an essential role in depression, it is very likely
      that autophagy may interact with the inflammatory process in the development and
      treatment of depression. Salvianolic acid B (SalB), a naturally occurring
      compound extracted from Salvia miltiorrhiza, contains anti-inflammatory and
      antidepression properties and has recently been proven to modulate autophagy. In
      this study, we sought to investigate whether autophagy is involved in the
      inflammation-induced depression and the antidepressant effects of SalB. METHODS:
      The effects of prolonged lipopolysaccharide (LPS) treatment and SalB
      administration on behavioral changes, neuroinflammation, autophagic markers and
      NLRP3 activation in rat hippocampus were determined by using behavioral tests,
      real-time PCR analysis, western blot, and immunostaining. RESULTS: Our data
      showed that periphery immune challenge by LPS for 2 weeks successfully induced
      the rats to a depression-like state, accompanied with enhanced expression of pro
      inflammatory cytokines and NLRP3 inflammasome activation. Interestingly,
      autophagic markers, including Beclin-1, and the ratio of LC3II to LC3I were
      suppressed following prolonged LPS exposure. Meanwhile, co-treatment with SalB
      showed robust antidepressant effects and ameliorated the LPS-induced
      neuroinflammation. Additionally, SalB restored the compromised autophagy and
      overactivated NLRP3 inflammasome in LPS-treated rats. CONCLUSIONS: Collectively,
      these data suggest that autophagy may interact with NLRP3 activation to
      contribute to the development of depression, whereas SalB can promote autophagy
      and induce the clearance of NLRP3, thereby resulting in neuroprotective and
      antidepressant actions.

PMID- 29212500
TI  - Correction to: Adenosine stress CMR T1-mapping detects early microvascular
      dysfunction in patients with type 2 diabetes mellitus without obstructive
      coronary artery disease.
AB  - In the original publication of this article [1] Fig. 1 was incorrect due to the
      use of a colour bar with wrong range in error.

PMID- 29212499
TI  - Radiotherapy plus temozolomide in elderly patients with glioblastoma: a "real
      life" report.
AB  - BACKGROUND: The optimization of the management for elderly glioblastoma patients
      is crucial given the demographics of aging in many countries. We report the
      outcomes for a "real-life" patient cohort (i.e. unselected) comprising
      consecutive glioblastoma patients aged 70 years or more, treated with different
      radiotherapy +/- temozolomide regimens. METHODS: From 2003 to 2016, 104 patients
      >= 70 years of age, consecutively treated by radiotherapy for glioblastoma, were
      included in this study. All patients were diagnosed with IDH-wild type
      glioblastoma according to pathological criteria. RESULTS: Our patient cohort
      comprised 51 female patients (49%) and 53 male. The median cohort age was 75
      years (70-88), and the median Karnofsky performance status (KPS) was 70 (30-100).
      Five (5%) patients underwent macroscopic complete resection, 9 (9%) had partial
      resection, and 90 (86%), a stereotactic biopsy. The MGMT promoter was methylated
      in 33/73 cases (45%). Fifty-two (50%), 38 (36%), and 14 (14%) patients were
      categorized with RPA scores of III, IV, and I-II. Thirty-three (32%) patients
      received normofractionated radiotherapy (60 Gy, 30 sessions) with temozolomide
      (Stupp), 37 (35%) received hypofractionated radiotherapy (median dose 40 Gy, 15
      sessions) with temozolomide (HFRT + TMZ), and 34 (33%) HFRT alone. Patients
      receiving only HFRT were significantly older, with lower KPSs. The median overall
      survival (OS; all patients) was 5.2 months. OS rates at 12, 18, and 24 months,
      were 19%, 12%, and 5%, respectively, with no statistical differences between
      patients receiving Stupp or HFRT + TMZ (P = 0.22). In contrast, patients
      receiving HFRT alone manifested a significantly shorter survival time (3.9 months
      vs. 5.9 months, P = 0.018). In multivariate analyses, the prognostic factors for
      OS were: i) the type of surgery (HR: 0.47 [0.26-0.86], P = 0.014), ii) RPA class
      (HR: 2.15 [1.17-3.95], P = 0.014), and iii) temozolomide use irrespective of
      radiotherapy schedule (HR: 0.54 [0.33-0.88], P < 0.02). MGMT promoter methylation
      was neither a prognostic nor a predictive factor. CONCLUSIONS: These outcomes
      agree with the literature in terms of optimal surgery and the use of HFRT as a
      standard treatment for elderly GBM patients. Our study emphasizes the potential
      benefit of using temozolomide with radiotherapy in a real-life cohort of elderly
      GBM patients, irrespective of their MGMT status.

PMID- 29212501
TI  - Equity implications for sanitation from recent health and nutrition evidence.
AB  - Recent evidence points to the possible underestimation of the health and
      nutrition impact of sanitation. Community sanitation coverage may first need to
      reach thresholds in the order of 60% or higher, to optimize health and nutrition
      gains. Increasing coverage of sanitation to levels below 60% of community
      coverage may not result in substantial gains. For example, moving Indonesia from
      60% to 100% improved sanitation coverage could significantly reduce diarrhoea in
      children under 5 years old (by an estimated 24% reduction in odds ratio for child
      diarrhoea morbidity) with gains split equally by reaching underserved communities
      and the unserved within communities. We review the implications of these results
      across three levels of program implementation - from micro level approaches (that
      support communities to achieve open defecation-free status), to meso level (sub
      national implementation) to macro level approaches for the national enabling
      environment and the global push to the Sustainable Development Goals. We found
      significant equity implications and recommend that future studies focus more
      extensively on community coverage levels and verified community open defecation
      free status rather than household access alone. Sanitation practitioners may
      consider developing phased approaches to improving water, sanitation and hygiene
      in communities while prioritizing the unserved or underserved.

PMID- 29212502
TI  - A spatial analysis of dietary patterns in a large representative population in
      the north of The Netherlands - the Lifelines cohort study.
AB  - BACKGROUND: Diet is an important modifiable risk factor for chronic diseases. In
      the search for effective strategies to improve dietary patterns in order to
      promote healthy ageing, new approaches considering contextual factors in public
      health medicine are warranted. The aim of this study is to examine the spatial
      clustering of dietary patterns in a large representative sample of adults.
      METHODS: Dietary patterns were defined on the basis of a 111 item Food Frequency
      Questionnaire among n = 117,570 adults using principal components analysis. We
      quantified the spatial clustering of dietary pattern scores at the neighborhood
      level using the Global Moran's I spatial statistic, taking into consideration
      individual demographic and (neighborhood) socioeconomic indicators. RESULTS: Four
      dietary patterns explaining 27% of the variance in dietary data were extracted in
      this population and named the "bread and cookies" pattern, the "snack" pattern,
      the "meat and alcohol" pattern and the "vegetable, fruit and fish" pattern.
      Significant spatial clustering of high (hot spot) and low (cold spot) dietary
      pattern scores was found for all four dietary patterns irrespective of age and
      gender differences. Educational attainment and neighborhood income explained the
      global clustering to some extent, although clustering at smaller regional scales
      persisted. CONCLUSION: The significant region-specific hot and cold spots of the
      four dietary patterns illustrate the existence of regional "food cultures" and
      underscore the need for interventions targeted at the sub-national level in order
      to tackle unhealthy dietary behavior and to stimulate people to make healthy
      dietary choices.

PMID- 29212504
TI  - Socioeconomic factors associated with cessation of injection drug use among
      street-involved youth.
AB  - BACKGROUND: Although the initiation of injection drug use has been well
      characterized among at-risk youth, factors that support or impede cessation of
      injection drug use have received less attention. We sought to identify
      socioeconomic factors associated with cessation of injection drug use among
      street-involved youth. METHODS: From September 2005 to May 2015, data were
      collected from the At-Risk Youth Study (ARYS), a prospective cohort study of
      street-involved youth in Vancouver, Canada. Multivariate extended Cox regression
      was utilized to identify socioeconomic factors associated with cessation of
      injection drug use for six months or longer among youth who were actively
      injecting. RESULTS: Among 383 participants, 171 (44.6%) youth reported having
      ceased injection (crude incidence density 22 per 100 person-years; 95% confidence
      interval [CI], 19-26) at some point during study follow-up. Youth who had
      recently dealt drugs (adjusted hazard ration [AHR], 0.50; 95% CI, 0.29-0.87),
      engaged in prohibited street-based income generation (AHR, 0.41; 95% CI, 0.24
      0.69), and engaged in illegal income generating activities (AHR, 0.19; 95% CI,
      0.06-0.61) were significantly less likely to report cessation of injection drug
      use. CONCLUSIONS: Our findings suggest that socioeconomic factors, in particular
      engagement in prohibited street-based and illegal income generating activities,
      may pose barriers to ceasing injection drug use among this population. Effort to
      improve access to stable and secure income, as well as employment opportunities
      may assist youth in transitioning away from injection drug use. TRIAL
      REGISTRATION: Our study is not a randomized controlled trial; thus the trial
      registration is not applicable.

PMID- 29212503
TI  - Synergistic antitumor interaction between valproic acid, capecitabine and
      radiotherapy in colorectal cancer: critical role of p53.
AB  - BACKGROUND: Recurrence with distant metastases has become the predominant pattern
      of failure in locally advanced rectal cancer (LARC), thus the integration of new
      antineoplastic agents into preoperative fluoropyrimidine-based chemo-radiotherapy
      represents a clinical challenge to implement an intensified therapeutic strategy.
      The present study examined the combination of the histone deacetylase inhibitor
      (HDACi) valproic acid (VPA) with fluoropyrimidine-based chemo-radiotherapy on
      colorectal cancer (CRC) cells. METHODS: HCT-116 (p53-wild type), HCT-116 p53-/-
      (p53-null), SW620 and HT29 (p53-mutant) CRC cell lines were used to assess the
      antitumor interaction between VPA and capecitabine metabolite 5'-deoxy-5
      fluorouridine (5'-DFUR) in combination with radiotherapy and to evaluate the role
      of p53 in the combination treatment. Effects on proliferation, clonogenicity and
      apoptosis were evaluated, along with gammaH2AX foci formation as an indicator for
      DNA damage. RESULTS: Combined treatment with equipotent doses of VPA and 5'-DFUR
      resulted in synergistic effects in CRC lines expressing p53 (wild-type or
      mutant). In HCT-116 p53-/- cells we observed antagonist effects. Radiotherapy
      further potentiated the antiproliferative, pro-apoptotic and DNA damage effects
      induced by 5'-DFUR/VPA combination in p53 expressing cells. CONCLUSIONS: These
      results highlighted the role of VPA as valuable candidate to be added to
      preoperative chemo-radiotherapy in LARC. On these bases we launched the ongoing
      phase I/II study of VPA and short-course radiotherapy plus capecitabine as
      preoperative treatment in low-moderate risk rectal cancer (V-shoRT-R3).

PMID- 29212505
TI  - Do patients with schizophreniform and bipolar disorders show an intrathecal,
      polyspecific, antiviral immune response? A pilot study.
AB  - BACKGROUND: We previously described inflammatory cerebrospinal fluid (CSF)
      alterations in a subgroup of patients with schizophreniform disorders and the
      synthesis of polyspecific intrathecal antibodies against different neurotropic
      infectious pathogens in some patients with bipolar disorders. Consequently, we
      have measured the prevalence of a positive MRZ reaction (MRZR)-a marker for a
      polyspecific, antiviral, intrathecal, humoral immune response composed of three
      antibody indices for the neurotropic viruses of measles (M), rubella (R), and
      varicella zoster (Z)-in these patients. METHODS: We analyzed paired CSF and serum
      samples of 39 schizophreniform and 39 bipolar patients. For comparison, we used a
      group of 48 patients with other inflammatory neurological disorders (OIND) and a
      cohort of 203 multiple sclerosis (MS) patients. RESULTS: We found a positive MRZR
      in two patients with schizophreniform disorders (5.1%); both suffered from
      schizodepressive disorders without any other signs suggestive of MS. None of the
      bipolar patients (0%) and four members of the OIND group (8.3%) showed a positive
      MRZR. In the MS cohort, a positive MRZR was found significantly more frequently
      [in 99 patients (48.8%)] than in the other patient groups (p > 0.001). In
      summary, we did not find a positive MRZR in a relevant subgroup of patients with
      schizophreniform or bipolar disorders. CONCLUSIONS: Our results indicate that the
      MRZR is highly specific to MS. Nevertheless, two schizodepressive patients also
      had a positive MRZR. This finding corresponds to the few MRZR-positive patients
      with OIND or other autoimmune disorders with central nervous involvement,
      implicating that the MRZR specificity for MS is high, but not 100%.

PMID- 29212506
TI  - Chromosome 9p copy number gains involving PD-L1 are associated with a specific
      proliferation and immune-modulating gene expression program active across major
      cancer types.
AB  - BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of
      the most promising approaches of immunotherapy for various cancer types. However,
      immune checkpoint inhibition is successful only in subpopulations of patients
      emphasizing the need for powerful biomarkers that adequately reflect the complex
      interaction between the tumor and the immune system. Recently, recurrent copy
      number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer
      types including lung cancer, melanoma, bladder cancer, head and neck cancer,
      cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian
      cancer, and triple-negative breast cancer. METHODS: Here, we applied functional
      genomics to analyze global mRNA expression changes associated with chromosome 9p
      gains. Using the TCGA data set, we identified a list of 75 genes that were
      strongly up-regulated in tumors with chromosome 9p gains across many cancer
      types. RESULTS: As expected, the gene set was enriched for chromosome 9p and in
      particular chromosome 9p24 (36 genes and 23 genes). Furthermore, we found
      enrichment of two expression programs derived from genes within and beyond 9p:
      one implicated in cell cycle regulation (22 genes) and the other implicated in
      modulation of the immune system (16 genes). Among these were specific cytokines
      and chemokines, e.g. CCL4, CCL8, CXCL10, CXCL11, other immunoregulatory genes
      such as IFN-G and IDO1 as well as highly expressed proliferation-related kinases
      and genes including PLK1, TTK, MELK and CDC20 that represent potential drug
      targets. CONCLUSIONS: Collectively, these data shed light on mechanisms of immune
      escape and stimulation of proliferation in cancer with PD-L1 CNG and highlight
      additional vulnerabilities that may be therapeutically exploitable.

PMID- 29212507
TI  - Housing and overdose: an opportunity for the scale-up of overdose prevention
      interventions?
AB  - BACKGROUND: North America is currently experiencing an overdose epidemic due to a
      significant increase of fentanyl-adulterated opioids and related analogs.
      Multiple jurisdictions have declared a public health emergency given the
      increasing number of overdose deaths. In the province of British Columbia (BC) in
      Canada, people who use drugs and who are unstably housed are disproportionately
      affected by a rising overdose crisis, with close to 90% of overdose deaths
      occurring indoors. Despite this alarming number, overdose prevention and response
      interventions have yet to be widely implemented in a range of housing settings.
      OVERDOSE PREVENTION INTERVENTIONS: There are few examples of overdose prevention
      interventions in housing environments. In BC, for example, there are peer-led
      naloxone training and distribution programs targeted at some housing
      environments. There are also "supervised" spaces such as overdose prevention
      sites (similar to supervised consumption sites (SCS)) located in some housing
      environments; however, their coverage remains limited and the impacts of these
      programs are unclear due to the lack of evaluation work undertaken to date. A
      small number of SCS exist globally in housing environments (e.g., Germany), but
      like overdose prevention sites in BC, little is known about the design or
      effectiveness, as they remain under-evaluated. CONCLUSIONS: Implementing SCS and
      other overdose prevention interventions across a range of housing sites provides
      multiple opportunities to address overdose risk and drug-related harms for
      marginalized people who use drugs. Given the current overdose crisis rising
      across North America, and the growing evidence of the relationship between
      housing and overdose, the continued implementation and evaluation of novel
      overdose prevention interventions in housing environments should be a public
      health priority. A failure to do so will simply perpetuate what has proven to be
      a devastating epidemic of preventable death.

PMID- 29212508
TI  - Health-related quality of life among adults with diverse rare disorders.
AB  - BACKGROUND: Twenty-five to 30 million Americans live with a rare disease (RD) and
      share challenges unique to RD. The majority of research on RDs has focused on
      etiology, treatment and care, while the limited health-related quality of life
      (HRQL) research has been restricted to single RDs, small samples, or non
      validated measures. This study reports HRQL among adults with diverse RDs, and
      compares their scores to those of the U.S. population and people with common
      chronic health conditions. METHODS: We conducted a cross-sectional survey of
      adults living in the U.S. diagnosed with any RD. Participants were recruited
      through RD organizations and completed the online survey between December 2016
      and May 2017 (n = 1218). HRQL was assessed using the standardized Patient
      Reported Outcomes Measurement Information System (PROMIS). RDs were classified
      into categories defined by Orphanet. Means and 95% confidence intervals were
      calculated for the main sample and for RD categories and were compared to
      published U.S. population norms and common chronic disease norms.
      Intercorrelations were conducted between HRQL, demographics, and RD experiences.
      RESULTS: When compared to the norms for the U.S. population and for those with
      common chronic diseases, mean HRQL scores were significantly poorer across all
      six PROMIS domains for the main sample, and were usually poorer when analyzed by
      sub-sets of specific RD classifications. People with rare systemic and
      rheumatologic, neurological, and immune diseases had the poorest HRQL.
      Participants had poorer HRQL if they had multiple RDs, lower income, were female,
      or older. Having symptoms longer was associated with worse HRQL, however, having
      a formal diagnosis longer was associated with better HRQL. CONCLUSIONS: This
      study is the first to examine HRQL in a large, heterogeneous sample of RDs using
      validated measures. There is a significant disparity in HRQL among people with RD
      compared to the general population and people with common chronic diseases. Poor
      HRQL could be attributed to challenges accessing diagnoses, medical information,
      treatment, psychosocial support, and coping with stigma and uncertainty. As most
      individuals with RDs will not be cured in their lifetimes, identifying ways to
      improve HRQL is crucial to patient-centered care and should be a funding
      priority.

PMID- 29212509
TI  - Incremental cost and cost-effectiveness of low-dose, high-frequency training in
      basic emergency obstetric and newborn care as compared to status quo: part of a
      cluster-randomized training intervention evaluation in Ghana.
AB  - BACKGROUND: Low-dose, high-frequency (LDHF) training is a new approach best
      practices to improve clinical knowledge, build and retain competency, and
      transfer skills into practice after training. LDHF training in Ghana is an
      opportunity to build health workforce capacity in critical areas of maternal and
      newborn health and translate improved capacity into better health outcomes.
      METHODS: This study examined the costs of an LDHF training approach for basic
      emergency obstetric and newborn care and calculates the incremental cost
      effectiveness of the LDHF training program for health outcomes of newborn
      survival, compared to the status quo alternative of no training. The costs of
      LDHF were compared to costs of traditional workshop-based training per provider
      trained. Retrospective program cost analysis with activity-based costing was used
      to measure all resources of the LDHF training program over a 3-year analytic time
      horizon. Economic costs were estimated from financial records, informant
      interviews, and regional market prices. Health effects from the program's impact
      evaluation were used to model lives saved and disability-adjusted life years
      (DALYs) averted. Uncertainty analysis included one-way and probabilistic
      sensitivity analysis to explore incremental cost-effectiveness results when
      fluctuating key parameters. RESULTS: For the 40 health facilities included in the
      evaluation, the total LDHF training cost was $823,134. During the follow-up
      period after the first LDHF training-1 year at each participating facility
      approximately 544 lives were saved. With deterministic calculation, these
      findings translate to $1497.77 per life saved or $53.07 per DALY averted.
      Probabilistic sensitivity analysis, with mean incremental cost-effectiveness
      ratio of $54.79 per DALY averted ($24.42-$107.01), suggests the LDHF training
      program as compared to no training has 100% probability of being cost-effective
      above a willingness to pay threshold of $1480, Ghana's gross national income per
      capita in 2015. CONCLUSION: This study provides insight into the investment of
      LDHF training and value for money of this approach to training in-service
      providers on basic emergency obstetric and newborn care. The LDHF training
      approach should be considered for expansion in Ghana and integrated into existing
      in-service training programs and health system organizational structures for
      lower cost and more efficiency at scale.

PMID- 29212510
TI  - Factors affecting treatment outcome in patients with idiopathic nonspecific
      interstitial pneumonia: a nationwide cohort study.
AB  - BACKGROUND: The effects of corticosteroid-based therapy in patients with
      idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting
      treatment outcome, are not fully understood. We aimed to investigate the long
      term treatment response and factors affecting the treatment outcome in iNSIP
      patients from a multi-center study in Korea. METHODS: The Korean interstitial
      lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients
      were divided into two groups to compare the treatment response: response group
      (forced vital capacity (FVC) improves >=10% after 1 year) and non-response group
      (FVC <10%). Factors affecting treatment response were evaluated by multivariate
      logistic regression analysis. RESULTS: A total of 261 patients with iNSIP were
      enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid
      treatment was performed in 86 patients. The treatment group showed a significant
      improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume
      (FEV1), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p
      < 0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related
      with lung function improvement. Sero-positivity ANA was significantly lower in
      the response group (p = 0.013), compared to that in the non-response group. A
      shorter duration of respiratory symptoms at diagnosis was significantly
      associated with a good response to treatment (p = 0.018). CONCLUSION: Treatment
      with corticosteroids and/or immunosuppressants improved lung function in iNSIP
      patients, which was more pronounced in sero-negative ANA and shorter symptom
      duration patients. These findings suggest that early treatment should be
      considered in iNSIP patients, even in an early disease stage.

PMID- 29212511
TI  - Comparing the Chinese versions of two knee-specific questionnaires (IKDC and
      KOOS): reliability, validity, and responsiveness.
AB  - BACKGROUND: The International Knee Documentation Committee Subjective Knee Form
      (IKDC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) are knee
      specific questionnaires that have been widely used and translated into numerous
      languages. However, the differences in the psychometric properties between the
      Chinese IKDC and KOOS remain unclear. The purpose of this study was to conduct a
      cross-cultural adaptation of the Chinese IKDC and Chinese KOOS and to compare the
      psychometric properties of these two measures in patients with various knee
      injuries from the acute stage up to 12 weeks after receiving treatment. METHODS:
      The original IKDC and KOOS were translated into Chinese based on the guidelines
      of cross-cultural adaptation and translation protocols. One hundred and seventy
      three patients with various knee injuries were recruited in this study and
      completed both Chinese IKDC and Chinese KOOS as well as a generic health status
      questionnaire (Chinese Short Form-36 [SF-36]). The reliability, internal
      consistency, content validity, convergent and divergent validity and
      responsiveness of both IKDC and KOOS were assessed with appropriate indices.
      RESULTS: The Chinese IKDC showed excellent reliability (ICC = 0.97) and strong
      internal consistency (Cronbach alpha = 0.87). The Chinese KOOS also presented
      good reliability with ICCs ranging from 0.89 to 0.95 and internal consistency
      (Cronbach alpha coefficients ranging from 0.76 to 0.97). The content validity of
      these two questionnaires were excellent, yielding no floor or ceiling effects.
      Both the Chinese IKDC and KOOS were highly associated with the physical component
      summary (PCS) score and weakly related to the mental component summary (MCS)
      score of the SF-36. Responsiveness to change was large (effect size =0.95) for
      the Chinese IKDC and moderate (effect sizes = 0.49~0.60) at 12-week after
      physical therapy. CONCLUSION: Both the Chinese IKDC and KOOS demonstrated good
      psychometric properties. However, the Chinese IKDC was more sensitive to changes
      over a period of 2, 4, 8, 12 weeks of physical therapy than the Chinese KOOS. The
      ROC analyses revealed a value of area under the curve (0.83 for the Chinese IKDC
      and 0.67-0.79 for the subscales of Chinese KOOS). Minimal clinically important
      difference values were 9.8 for the Chinese IKDC and 0.79, 0.76, 0.76, 0.76, 0.67
      for the Symptoms, Pain, Activities of Daily Living, Sport/Recreation, and Quality
      of Life subscales of Chinese KOOS, respectively. The current study provides
      information for clinicians and researchers to use these appraisal tools for
      Chinese-speaking patients with various knee disorders.

PMID- 29212512
TI  - Correction to: Parma consensus statement on metabolic disruptors.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that the thirteenth author of this article has had their name spelt
      incorrectly. In the original article the spelling "Laura Rizzir" was used. In
      fact the correct spelling should be "Laura Rizzi".

PMID- 29212514
TI  - Correction to: Characterization of skin function associated with obesity and
      specific correlation to local/systemic parameters in American women.
AB  - Following publication of the original article [1], the authors identified an
      error. In the description in Fig. 1b the "solid line" "dashed line" should be
      exchanged. The original article has been updated.

PMID- 29212513
TI  - Cardiac amyloidosis is prevalent in older patients with aortic stenosis and
      carries worse prognosis.
AB  - BACKGROUND: Non-invasive cardiac imaging allows detection of cardiac amyloidosis
      (CA) in patients with aortic stenosis (AS). Our objective was to estimate the
      prevalence of clinically suspected CA in patients with moderate and severe AS
      referred for cardiovascular magnetic resonance (CMR) in age and gender
      categories, and assess associations between AS-CA and all-cause mortality.
      METHODS: We retrospectively identified consecutive AS patients defined by
      echocardiography referred for further CMR assessment of valvular, myocardial, and
      aortic disease. CMR identified CA based on typical late-gadolinium enhancement
      (LGE) patterns, and ancillary clinical evaluation identified suspected CA.
      Survival analysis with the Log rank test and Cox regression compared associations
      between CA and mortality. RESULTS: There were 113 patients (median age 74 years,
      Q1-Q3: 62-82 years), 96 (85%) with severe AS. Suspected CA was present in 9
      patients (8%) all > 80 years. Among those over the median age of 74 years, the
      prevalence of CA was 9/57 (16%), and excluding women, the prevalence was 8/25
      (32%). Low-flow, low-gradient physiology was very common in CA (7/9 patients or
      78%). Over a median follow-up of 18 months, 40 deaths (35%) occurred. Mortality
      in AS + CA patients was higher than AS alone (56% vs. 20% at 1-year, log rank
      15.0, P < 0.0001). Adjusting for aortic valve replacement modeled as a time
      dependent covariate, Society of Thoracic Surgery predicted risk of mortality,
      left ventricular ejection fraction, CA remained associated with all-cause
      mortality (HR = 2.92, 95% CI = 1.09-7.86, P = 0.03). CONCLUSIONS: Suspected CA
      appears prevalent among older male patients with AS, especially with low flow,
      low gradient AS, and associates with all-cause mortality. The importance of
      screening for CA in older AS patients and optimal treatment strategies in those
      with CA warrant further investigation, especially in the era of transcatheter
      aortic valve implantation.

PMID- 29212515
TI  - Psychometric properties of morning joint stiffness duration and severity measures
      in patients with moderately to severely active rheumatoid arthritis.
AB  - BACKGROUND: To assess the measurement properties of two single-item patient
      reported outcome (PRO) measures that assessed the length of time (in minutes) and
      severity of morning joint stiffness (MJS) experienced each day. METHODS: Data
      from two Phase 3, randomized placebo-controlled (and active-controlled [RA
      BEAM]), clinical studies assessing the safety and efficacy of baricitinib in
      adults with moderately to severely active rheumatoid arthritis (RA) were used to
      evaluate the psychometric properties of the Duration of MJS and Severity of MJS
      PROs. RESULTS: Test-retest reliability of Duration of MJS and Severity of MJS was
      supported through large intraclass correlation coefficients among stable patients
      (coefficient range for both studies: 0.88 to 0.93). In support of construct
      validity, moderate correlations were evidenced between Duration of MJS and other
      related patient- and clinician-reported assessments of RA symptoms and patient
      functioning, whereas moderate-to-strong correlations were evidenced between these
      same patient- and clinician-reported assessments and Severity of MJS.
      Statistically significant differences between the median and mean values of
      Duration of MJS and Severity of MJS for differing categories of RA disease
      severity supported known-groups validity. Finally, large and statistically
      significant differences in change scores from Day 1 to Week 12 for patients
      defined as responders versus non-responders using the American College of
      Rheumatology 20 criteria supported the responsiveness of both PROs. CONCLUSION:
      Duration of MJS and Severity of MJS PROs demonstrated reliability, validity, and
      responsiveness in adults with moderately to severely active RA, supporting the
      measurement of these key symptoms in clinical trials.

PMID- 29212516
TI  - A finite element model of the lower limb during stance phase of gait cycle
      including the muscle forces.
AB  - BACKGROUND: Results of finite element (FE) analyses can give insight into
      musculoskeletal diseases if physiological boundary conditions, which include the
      muscle forces during specific activities of daily life, are considered in the FE
      modelling. So far, many simplifications of the boundary conditions are currently
      made. This study presents an approach for FE modelling of the lower limb for
      which muscle forces were included. METHODS: The stance phase of normal gait was
      simulated. Muscle forces were calculated using a musculoskeletal rigid body (RB)
      model of the human body, and were subsequently applied to a FE model of the lower
      limb. It was shown that the inertial forces are negligible during the stance
      phase of normal gait. The contact surfaces between the parts within the knee were
      modelled as bonded. Weak springs were attached to the distal tibia for numerical
      reasons. RESULTS: Hip joint reaction forces from the RB model and those from the
      FE model were similar in magnitude with relative differences less than 16%. The
      forces of the weak spring were negligible compared to the applied muscle forces.
      The maximal strain was 0.23% in the proximal region of the femoral diaphysis and
      1.7% in the contact zone between the tibia and the fibula. CONCLUSIONS: The
      presented approach based on FE modelling by including muscle forces from inverse
      dynamic analysis of musculoskeletal RB model can be used to perform analyses of
      the lower limb with very realistic boundary conditions. In the present form, this
      model can be used to better understand the loading, stresses and strains of bones
      in the knee area and hence to analyse osteotomy fixation devices.

PMID- 29212517
TI  - Is hematoxylin-eosin staining in rectal mucosal and submucosal biopsies still
      useful for the diagnosis of Hirschsprung disease?
AB  - BACKGROUND: Hematoxylin-eosin (HE) staining of a full-thickness rectal wall
      fragment is classically used for the diagnosis of Hirschsprung disease (HD).
      However, this technique requires large fragments for a better diagnosis.
      Additionally, the histochemical and immunohistochemical methods of staining small
      fragments of rectal mucosal and submucosal biopsies are not available in all
      centers. Therefore, the possibility of diagnosing HD through HE staining in these
      biopsies could be a valuable alternative for centers that do not have more
      specific techniques. The objectives of the current investigation were to evaluate
      the concordance of the results obtained by HE staining and the calretinin method
      with acetylcholinesterase (AChE) activity in fragments of mucosa and submucosa in
      the diagnosis of HD. METHODS: For this study, 50 cases from our laboratory were
      selected. The tissue material was embedded in paraffin. Sixty levels of each
      fragment were utilized for HE, and the other 3 levels were used for calretinin.
      These slides were analyzed under the microscope, photographed and classified as
      either positive for HD when no ganglion cells were found with nerve trunks
      present or as negative when ganglion cells were found. The results from reading
      the slides were compared with those of AChE. RESULTS: Of the 50 cases evaluated
      by the HE technique, only 5 contradicted the diagnosis based on AChE, with a
      Kappa value of 0.800 and an accuracy of 90%. In the comparison between calretinin
      and AChE, 8 cases were discordant, with a Kappa value of 0.676 and an accuracy of
      84%. CONCLUSIONS: The concordance of results from AChE and HE methods was
      satisfactory, allowing for the potential use of the HE method for fragments of
      mucosa and submucosa as a valid alternative in the diagnosis of HD. The
      immunohistochemical technique of calretinin did not show good agreement with the
      AChE activity in our study.

PMID- 29212518
TI  - Effect of low and high HDL-C levels on the prognosis of lupus nephritis patients:
      a prospective cohort study.
AB  - BACKGROUND: Few data has been available on the effect of serum HDL-C levels on
      the prognosis of lupus nephritis (LN) patients. The present study therefore aimed
      to explore the effect of serum HDL-C levels on LN patients. METHODS: We included
      775 patients with follow-up information registered in an LN database between 1
      January 2006 and 31 December 2011. The patients were divided into groups with
      low, intermediate and high HDL-C, according to NCEP ATPIII criteria. Cox
      regression analyses were used to explore the effects of HDL-C levels on end-stage
      renal disease (ESRD), all-cause mortality and cardiovascular disease (CVD)
      mortality. RESULTS: During a median follow-up of 56 months (3-206 months), 71
      (9.2%) had ESRD. 84 (10.8%) deaths occurred, 17 (20.2%) of which were due to CVD.
      There was no statistically significant association of HDL-C category or
      continuous HDL-C levels with ESRD in the total cohort, but in subgroup analyses
      by eGFR, with each 0.1 mmol/L increase in HDL-C level, adjusted HRs for ESRD were
      0.92 (95% CI: 0.83-1.04, P = 0.173) for eGFR >=60 ml/min/1.73m2 and 1.11 (95% CI:
      1.01-1.23, P = 0.036) for eGFR <60 ml/min/1.73m2. The effect of the interaction
      between eGFR category and serum HDL-C level on ESRD was statistically significant
      (beta = -1.738, P = 0.005). Low HDL-C was associated with all-cause mortality (HR
      = 2.16, 95% CI: 1.06-4.40, P = 0.033) with intermediate HDL-C as reference
      category after adjusting for several variables. CONCLUSIONS: Our results
      demonstrate that high HDL-C levels were associated with increased risk of ESRD in
      LN patients with advanced renal dysfunction. While low HDL-C levels were
      associated with increased risk of all-cause mortality in LN patients. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT03001973 , 22 December 2016
      retrospectively registered.

PMID- 29212519
TI  - GPER mediates the angiocrine actions induced by IGF1 through the HIF-1alpha/VEGF
      pathway in the breast tumor microenvironment.
AB  - BACKGROUND: The G protein estrogen receptor GPER/GPR30 mediates estrogen action
      in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs),
      which are key components of microenvironment driving tumor progression. GPER is a
      transcriptional target of hypoxia inducible factor 1 alpha (HIF-1alpha) and
      activates VEGF expression and angiogenesis in hypoxic breast tumor
      microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic
      effects, has been shown to activate GPER in breast cancer cells. METHODS: We
      analyzed gene expression data from published studies representing almost 5000
      breast cancer patients to investigate whether GPER and IGF1 signaling establish
      an angiocrine gene signature in breast cancer patients. Next, we used GPER
      positive but estrogen receptor (ER)-negative primary CAF cells derived from
      patient breast tumours and SKBR3 breast cancer cells to investigate the role of
      GPER in the regulation of VEGF expression and angiogenesis triggered by IGF1. We
      performed gene expression and promoter studies, western blotting and
      immunofluorescence analysis, gene silencing strategies and endothelial tube
      formation assays to evaluate the involvement of the HIF-1alpha/GPER/VEGF
      signaling in the biological responses to IGF1. RESULTS: We first determined that
      GPER is co-expressed with IGF1R and with the vessel marker CD34 in human breast
      tumors (n = 4972). Next, we determined that IGF1/IGF1R signaling engages the
      ERK1/2 and AKT transduction pathways to induce the expression of HIF-1alpha and
      its targets GPER and VEGF. We found that a functional cooperation between HIF
      1alpha and GPER is essential for the transcriptional activation of VEGF induced
      by IGF1. Finally, using conditioned medium from CAFs and SKBR3 cells stimulated
      with IGF1, we established that HIF-1alpha and GPER are both required for VEGF
      induced human vascular endothelial cell tube formation. CONCLUSIONS: These
      findings shed new light on the essential role played by GPER in IGF1/IGF1R
      signaling that induces breast tumor angiogenesis. Targeting the multifaceted
      interactions between cancer cells and tumor microenvironment involving both GPCRs
      and growth factor receptors has potential in future combination anticancer
      therapies.

PMID- 29212520
TI  - The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the
      outcomes of HCV infection in a Chinese population.
AB  - BACKGROUND: Recently, human leukocyte antigen (HLA) class-II gene polymorphisms
      have been reported to be related to Hepatitis C virus (HCV) infection and
      chronicity. The objective of this study was to explore the relationship of HLA-DP
      rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection. METHODS: The
      rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV
      infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non
      HCV infection from the Chinese population using the ABI TaqMan allelic
      discrimination assay. RESULTS: Logistic regression analyses showed that the minor
      allele A of rs7453920 significantly increased the susceptibility of HCV infection
      in dominant model (adjusted OR = 1.33, 95% CI: 1.04-1.71, P = 0.026) and additive
      models (adjusted OR = 1.30, 95% CI: 1.06-1.60, P = 0.012). Rs9277535 A allele
      significantly increased the risk of chronic HCV infection in dominant model
      (adjusted OR = 1.52, 95% CI: 1.01-2.28, P = 0.046). Haplotype AA showed a higher
      risk of HCV infection than the most frequent haplotype GG (adjusted OR = 1.37,
      95% CI: 1.05-1.78, P = 0.018). CONCLUSION: The HLA-DQ rs7453920 and -DP rs9277535
      mutations were significantly associated with HCV infection susceptibility and
      chronicity, respectively.

PMID- 29212521
TI  - Prognostic factors of nasopharyngeal carcinoma patients in a tertiary referral
      hospital: a retrospective cohort study.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) exhibits a distinctive racial and
      geographic distribution. Many studies have reported varied significant prognostic
      factors affect the survival of NPC patients. Hence, this current study aimed to
      identify the prognostic factors of NPC patients registered in a tertiary referral
      hospital. METHODS: The records of one hundred and thirty-four NPC cases confirmed
      by histopathology in Hospital Universiti Sains Malaysia (USM) between 1st January
      1998 and 31st December 2007 that fulfilled the inclusion and exclusion criteria
      were retrospectively reviewed. Simple and multiple Cox proportional hazard
      regression analyses were performed to determine the significant prognostic
      factors affect the survival of NPC patients. RESULTS: The mean (SD) age of
      patients diagnosed with NPC was 48.12 (15.88) years with Malay was the largest
      ethnic group compared to other ethnicities. Most of patients had locally advanced
      stage IV (40.6%) and stage III (39.1%) of NPC. The overall median survival time
      of NPC patients was 31.30 months (95% CI 23.76, 38.84). The significant
      prognostic factors that influenced the survival of NPC patients were older age
      (HR 1.03, 95% CI 1.01, 1.04), metastases (HR 2.52, 95% CI 1.01, 6.28) and stage
      IV disease (HR 4.50, 95% CI 1.66, 9.88). CONCLUSION: Older age, the presence of
      metastases and late stage are significant prognostic factors that influence the
      survival of NPC. Therefore, it is important to provide education to public and to
      raise awareness to diagnose NPC at an earlier stage and before the presence of
      metastases.

PMID- 29212522
TI  - A systematic review of neonatal treatment intensity scores and their potential
      application in low-resource setting hospitals for predicting mortality, morbidity
      and estimating resource use.
AB  - BACKGROUND: Treatment intensity scores can predict mortality and estimate
      resource use. They may therefore be of interest for essential neonatal care in
      low resource settings where neonatal mortality remains high. We sought to
      systematically review neonatal treatment intensity scores to (1) assess the level
      of evidence on predictive performance in predicting clinical outcomes and
      estimating resource utilisation and (2) assess the applicability of the
      identified models to decision making for neonatal care in low resource settings.
      METHODS: We conducted a systematic search of PubMed, EMBASE (OVID), CINAHL,
      Global Health Library (Global index, WHO) and Google Scholar to identify studies
      published up until 21 December 2016. Included were all articles that used
      treatments as predictors in neonatal models. Individual studies were appraised
      using the CHecklist for critical Appraisal and data extraction for systematic
      Reviews of prediction Modelling Studies (CHARMS). In addition, Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) was used as a
      guiding framework to assess certainty in the evidence for predicting outcomes
      across studies. RESULTS: Three thousand two hundred forty-nine articles were
      screened, of which ten articles were included in the review. All of the studies
      were conducted in neonatal intensive care units with sample sizes ranging from 22
      to 9978, with a median of 163. Two articles reported model development, while
      eight reported external application of existing models to new populations. Meta
      analysis was not possible due heterogeneity in the conduct and reporting of the
      identified studies. Discrimination as assessed by area under receiver operating
      characteristic curve was reported for in-hospital mortality, median 0.84 (range
      0.75-0.96, three studies), early adverse outcome and late adverse outcome (0.78
      and 0.59, respectively, one study). CONCLUSION: Existing neonatal treatment
      intensity models show promise in predicting mortality and morbidity. There is
      however low certainty in the evidence on their performance in essential neonatal
      care in low resource settings as all studies had methodological limitations and
      were conducted in intensive care. The approach may however be developed further
      for low resource settings like Kenya because treatment data may be easier to
      obtain compared to measures of physiological status. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016034205.

PMID- 29212523
TI  - Relationship between maximum oxygen uptake and peripheral vasoconstriction in a
      cold environment.
AB  - BACKGROUND: Various individual characteristics affect environmental adaptability
      of a human. The present study evaluates the relationship between physical fitness
      and peripheral vasoconstriction in a cold environment. METHODS: Seven healthy
      male students (aged 22.0 years) participated in this study. Cold exposure tests
      consisted of supine rest for 60 min at 28  degrees C followed by 90 min at 10 
      degrees C. Rectal and skin temperatures at seven sites, oxygen consumption, and
      the diameter of a finger vein were measured during the experiment. Metabolic heat
      production, skin heat conductance, and the rate of vasoconstriction were
      calculated. Individual maximum oxygen consumption, a direct index of aerobic
      fitness, was measured on the day following the cold exposure test. RESULTS:
      Decreases in temperature of the hand negatively correlated with the changes in
      rectal temperature. Maximum oxygen consumption and the rate of vasoconstriction
      are positively correlated. Furthermore, pairs of the following three factors are
      also significantly correlated: rate of metabolic heat production, skin heat
      conductance, and the rate of vasoconstriction. CONCLUSION: The results of this
      study suggested that the capacity for peripheral vasoconstriction can be improved
      by physical exercise. Furthermore, when exposed to a cold environment, fitter
      individuals could maintain metabolic heat production at the resting metabolic
      level of a thermoneutral condition, as they correspondingly lost less heat.

PMID- 29212524
TI  - Successful management of retinal metastasis from renal cancer with everolimus in
      a monophthalmic patient: a case report.
AB  - BACKGROUND: The retina is an uncommon site for metastases, in particular from
      solid tumors. Some authors have reported a recent increase in the incidence of
      metastases in infrequent sites, such as brain or bone, probably due to the
      expanded treatment options and the resulting improved survival. Choroidal
      metastasis is the most common type of intraocular malignancy. The most common
      primary sites associated with choroidal metastasis are breast cancer in women and
      lung cancer in men. Treatment options are limited, but they must be discussed and
      adapted to the patient profile. CASES PRESENTATION: We report a case of a 62-year
      old Moroccan man with a history of monophthalmitis secondary to a war injury of
      30 years' duration. He has been followed for 28 months for metastatic clear-cell
      renal carcinoma. The first-line treatment was effective for 24 months, before
      disease progression as retinal metastasis and accentuation of lung metastases. A
      second-line treatment with everolimus resulted in marked improvement of symptoms,
      complete recovery of visual function, and partial response in retinal
      localization. CONCLUSIONS: Choroidal metastasis of renal cancer is a rare
      situation that must be actively sought in order to arrive at a suitable
      therapeutic approach.

PMID- 29212525
TI  - Establishing and characterizing patient-derived xenografts using pre-chemotherapy
      percutaneous biopsy and post-chemotherapy surgical samples from a prospective
      neoadjuvant breast cancer study.
AB  - BACKGROUND: Patient-derived xenografts (PDXs) are increasingly used in cancer
      research as a tool to inform cancer biology and drug response. Most available
      breast cancer PDXs have been generated in the metastatic setting. However, in the
      setting of operable breast cancer, PDX models both sensitive and resistant to
      chemotherapy are needed for drug development and prospective data are lacking
      regarding the clinical and molecular characteristics associated with PDX take
      rate in this setting. METHODS: The Breast Cancer Genome Guided Therapy Study
      (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III
      breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab
      followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies
      (PTB), we established and characterized PDXs from both primary (untreated) and
      residual (treated) tumors. Tumor take rate was defined as percent of patients
      with the development of at least one stably transplantable (passed at least for
      four generations) xenograft that was pathologically confirmed as breast cancer.
      RESULTS: Baseline PTB samples from 113 women were implanted with an overall take
      rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in
      triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal
      B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from
      those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The
      xenografts from 28 of these 31 patients were such that at least one of the
      xenografts generated had the same molecular subtype as the patient. Among the 35
      patients with residual tumor after NAC adequate for implantation, the take rate
      was 17.1%. PDX response to paclitaxel mirrored the patients' clinical response in
      all eight PDX tested. CONCLUSIONS: The generation of PDX models both sensitive
      and resistant to standard NAC is feasible and these models exhibit similar
      biological and drug response characteristics as the patients' primary tumors.
      Taken together, these models may be useful for biomarker discovery and future
      drug development.

PMID- 29212526
TI  - Structural and functional annotation of hypothetical proteins of human
      adenovirus: prioritizing the novel drug targets.
AB  - OBJECTIVE: Human adenoviruses are small double stranded DNA viruses that provoke
      vast array of human diseases. Next generation sequencing techniques increase
      genomic data of HAdV rapidly, which increase their serotypes. The complete genome
      sequence of human adenovirus shows that it contains large amount of proteins with
      unknown cellular or biochemical function, known as hypothetical proteins. Hence,
      it is indispensable to functionally and structurally annotate these proteins to
      get better understanding of the novel drug targets. The purpose was the
      characterization of 38 randomly retrieved hypothetical proteins through
      determination of their physiochemical properties, subcellular localization,
      function, structure and ligand binding sites using various sequence and structure
      based bioinformatics tools. RESULTS: Function of six hypothetical proteins
      P03269, P03261, P03263, Q83127, Q1L4D7 and I6LEV1 were predicted confidently and
      then used further for structure analysis. We found that these proteins may act as
      DNA terminal protein, DNA polymerase, DNA binding protein, adenovirus E3 region
      protein CR1 and adenoviral protein L1. Functional and structural annotation
      leading to detection of binding sites by means of docking analysis can indicate
      potential target for therapeutics to defeat adenoviral infection.

PMID- 29212527
TI  - Anemia is associated with incidence of dementia: a national health screening
      study in Korea involving 37,900 persons.
AB  - BACKGROUND: The aim of this study was to investigate whether anemia is associated
      with dementia incidence in the elderly. METHODS: Using the Korean National Health
      Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, we
      identified 66-year-old subjects (n = 37,900) who were free of dementia and
      stroke. Anemia (hemoglobin < 12 g/dl for women and < 13 g/dl for men) and the
      severity of anemia (mild, moderate, or severe) were defined using World Health
      Organization criteria. The incidence of dementia was identified using
      International Classification of Diseases, Tenth Revision, dementia diagnosis
      codes (F00, F01, F02, F03, and G30) with prescription of an antidementia drug.
      Cox proportional hazards regression models were used to assess HRs for dementia
      incidence according to anemia. RESULTS: After adjusting for sex, baseline
      cognitive state, body mass index, smoking status, household income, disability,
      depression, hypertension, diabetes, and dyslipidemia, we found a significant
      association between anemia and dementia incidence (adjusted HR 1.24; 95% CI 1.02
      1.51). The adjusted HRs for incidence of dementia according to the severity of
      anemia were 1.19 (95% CI 0.98-1.45) for those with mild anemia, 1.47 (95% CI 0.97
      2.21) for those with moderate anemia, and 5.72 (95% CI 1.84-17.81) for those with
      severe anemia, showing a significant p value for trend (p = 0.003). CONCLUSIONS:
      Anemia is an independent risk factor for dementia incidence, with a marked
      increase of risk associated with severe anemia.

PMID- 29212529
TI  - Bacteriological study of calf colisepticemia in Alage Dairy Farm, Southern
      Ethiopia.
AB  - OBJECTIVE: This study was designed to estimate the prevalence of E. coli which is
      the main cause of colisepticemia and the potential risk factors associated with
      the disease. A total of 74 calves less than 6 months age were selected for this
      study. For isolation and identification of E. coli, bacterial culture and
      biochemical tests were used. RESULT: Out of 74 calves selected for this study, 6
      (8.11%) were positive for septicemic E. coli. Higher prevalence of 5 (8.93%) was
      recorded in Holstein Friesian breed than Boran breed 1 (5.56%). However, breed
      showed no significant difference on E. coli infections (P > 0.05). Higher
      prevalence of E. coli revealed below age of 30 days (17.39%) than calves aged
      between 30 and 90 days (8.33%) and above 90 days (0.00%). However, statistical
      association showed no difference (P > 0.05). Parity showed a significant
      difference in prevalence of E. coli (P < 0.05) in which infection increased with
      number of parity. Sex of the animal showed no association with infection of the
      calves (P > 0.05). Diarrheic calves showed higher prevalence (33.3%) than non
      diarrheic calves (4.62%) with strong statistical association (P < 0.05). The
      present study showed a high prevalence of septicemic E. coli in the farm and
      intervention is strongly recommended.

PMID- 29212528
TI  - Effectiveness of robot-assisted training added to conventional rehabilitation in
      patients with humeral fracture early after surgical treatment: protocol of a
      randomised, controlled, multicentre trial.
AB  - BACKGROUND: The incidence of proximal humeral fractures increases with age. The
      functional recovery of the upper arm after such fractures is slow, and results
      are often disappointing. Treatment is associated with long immobilisation
      periods. Evidence-based exercise guidelines are missing. Loss of muscle mass as
      well as reduced range of motion and motor performance are common consequences.
      These losses could be partly counteracted by training interventions using robot
      assisted arm support of the affected arm derived from neurorehabilitation. Thus,
      shorter immobilisation could be reached. Thus far, this approach has been tested
      in only a few small studies. The aim of the present study is to examine whether
      assistive robotic training augmenting conventional occupational and physical
      therapy can improve functional shoulder outcomes. METHODS/DESIGN: Patients aged
      between 35 and 66 years with proximal humeral fracture and surgical treatment
      will be recruited at three different clinics in Germany and randomised into an
      intervention group and a control group. Participants will be assessed before
      randomisation and followed after completing an intervention period of 3 weeks and
      additionally after 3, 6 and 12 months. The baseline assessment will include
      cognition (Short Orientation-Memory-Concentration Test); level of pain in the
      affected arm; ability to work; gait speed (10-m walk); disability of the arm,
      shoulder and hand (Disabilities of the Arm, Shoulder and Hand Outcome Measure
      [DASH]); range of motion of the affected arm (goniometer measurement); visual
      acuity; and motor function of orthopaedic patients (Wolf Motor Function Test
      Orthopaedic version [WMFT-O]). Clinical follow-up directly after the intervention
      will include assessment of disability of the arm, shoulder and hand (DASH) as
      well as range of motion and motor function (WMFT-O). The primary outcome
      parameter will be the DASH, and the secondary outcome parameter will be the WMFT
      O. The long-term results will be assessed prospectively by postal follow-up. All
      patients will receive conventional occupational and physical therapy. The
      intervention group will receive additional robot-assisted training using the
      Armeo(r)Spring robot for 3 weeks. DISCUSSION: This study protocol describes a
      phase II, randomised, controlled, single-blind, multicentre intervention study.
      The results will guide and possibly improve methods of rehabilitation after
      proximal humeral fracture. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03100201 .
      Registered on 28 March 2017.

PMID- 29212530
TI  - Identifying genotype-phenotype relationships in biomedical text.
AB  - BACKGROUND: One important type of information contained in biomedical research
      literature is the newly discovered relationships between phenotypes and
      genotypes. Because of the large quantity of literature, a reliable automatic
      system to identify this information for future curation is essential. Such a
      system provides important and up to date data for database construction and
      updating, and even text summarization. In this paper we present a machine
      learning method to identify these genotype-phenotype relationships. No large
      human-annotated corpus of genotype-phenotype relationships currently exists. So,
      a semi-automatic approach has been used to annotate a small labelled training set
      and a self-training method is proposed to annotate more sentences and enlarge the
      training set. RESULTS: The resulting machine-learned model was evaluated using a
      separate test set annotated by an expert. The results show that using only the
      small training set in a supervised learning method achieves good results
      (precision: 76.47, recall: 77.61, F-measure: 77.03) which are improved by
      applying a self-training method (precision: 77.70, recall: 77.84, F-measure:
      77.77). CONCLUSIONS: Relationships between genotypes and phenotypes is biomedical
      information pivotal to the understanding of a patient's situation. Our proposed
      method is the first attempt to make a specialized system to identify genotype
      phenotype relationships in biomedical literature. We achieve good results using a
      small training set. To improve the results other linguistic contexts need to be
      explored and an appropriately enlarged training set is required.

PMID- 29212531
TI  - Etiology of respiratory tract infections in the community and clinic in Ilorin,
      Nigeria.
AB  - OBJECTIVE: Recognizing increasing interest in community disease surveillance
      globally, the goal of this study was to investigate whether respiratory viruses
      circulating in the community may be represented through clinical (hospital)
      surveillance in Nigeria. RESULTS: Children were selected via convenience sampling
      from communities and a tertiary care center (n = 91) during spring 2017 in
      Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain
      reaction. The majority (79.1%) of subjects were under 6 years old, of whom 46
      were infected (63.9%). A total of 33 of the 91 subjects had one or more
      respiratory tract virus; there were 10 cases of triple infection and 5 of
      quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus
      were the most common viruses in the clinical sample; present in 93.8% (15/16) of
      clinical subjects, and 6.7% (5/75) of community subjects (significant difference,
      p < 0.001). Coronavirus OC43 was the most common virus detected in community
      members (13.3%, 10/75). A different strain, Coronavirus OC 229 E/NL63 was
      detected among subjects from the clinic (2/16) and not detected in the community.
      This pilot study provides evidence that data from the community can potentially
      represent different information than that sourced clinically, suggesting the need
      for community surveillance to enhance public health efforts and scientific
      understanding of respiratory infections.

PMID- 29212532
TI  - Delivery of screening and brief intervention for unhealthy alcohol use in an
      urban academic Federally Qualified Health Center.
AB  - BACKGROUND: Screening and brief intervention (SBI) for unhealthy drinking has not
      been widely implemented in primary care partly due to reliance on physicians to
      perform it. METHODS: We implemented a model of nursing staff-delivered SBI for
      unhealthy drinking for adult patients receiving primary care at an academically
      affiliated Federally Qualified Health Center in the Bronx, NY. Our model
      consisted of nursing staff screening all patients with the alcohol use disorders
      identification test consumption questions (AUDIT-C) and, if screening positive,
      providing BI or referral to specialty services. We developed a clinical decision
      support tool integrated into the electronic health record to guide nursing staff
      and record SBI provision. To evaluate this model, we determined overall SBI
      delivery to patients and factors associated with receiving SBI. RESULTS: Between
      October 2013 and September 2014, 9119 unique adult patients made 24,285 visits.
      Patients were majority women (67.5%) and Hispanic/Latino (54.5%). Overall, 46.2%
      were screened, with 19.0-35.8% of eligible patients screened in each month.
      Increasing age (OR: 0.82 [95% CI 0.80-0.85] for a 10-year increase), female sex
      (OR: 0.83 [95% CI 0.77-0.91]), and chronic conditions like hypertension (OR: 0.62
      [95% CI 0.56-0.70]) and diabetes (OR: 0.66 [95% CI 0.58-0.75]), among others,
      were associated with a lower odds of being screened. Of all patients screened,
      225 (5.3%) screened positive and of those patients, 122 (54.2%) received a BI.
      Patients with higher AUDIT-C scores were more likely to receive a BI (OR: 1.24
      [95% CI 1.04-1.47] for a 1-point increase) and non-English speaking patients were
      less likely to receive a BI than those who spoke English (OR: 0.42 [95% CI 0.18
      0.97]). CONCLUSIONS: Our model of SBI resulted in screening of nearly half of all
      eligible patients and BI provision to over half of those screening positive.
      Future efforts to improve SBI delivery should focus on groups such as older
      adults, women, and those with chronic medical conditions.

PMID- 29212534
TI  - Engaging a rural community in identifying determinants of low birth weight and
      deciding on measures to improve low birth weight: an experience from a Sri Lankan
      study.
AB  - BACKGROUND: Involving communities in identifying and addressing determinants of
      their own health is effective in addressing complex problems, such as low birth
      weight (LBW). LBW is an important public health problem which has not improved
      significantly in Sri Lanka in the last 10 years. This study reports the ability
      of lay persons to identify and address determinants of LBW. METHODS: A health
      promotion intervention was conducted among 403 mothers registering at 26
      antenatal clinics in the district of Anuradhapura, in Sri Lanka. The components
      of a health promotion process-initiation, maintenance and continual monitoring,
      and re-direction towards greater effectiveness-were explained to the mothers.
      Inputs were initially provided through different methods to enable mothers'
      groups to identify determinants of LBW and to decide actions to address those
      identified determinants. The overall study was carried out over a period of 1
      year, of which the intervention phase took around 7 months. The mothers in the
      clinic group were encouraged to continue an ongoing process in smaller
      "neighborhood action committees" (NACs)-of which there were 71. The findings are
      based on field notes maintained during the process, analyzed using thematic
      analysis. RESULTS: Each group of mothers identified at least eight determinants
      of LBW at the first attempt (without first author's guidance), four of which
      corresponded with those already mentioned in published studies. Up to five other
      determinants were agreed, after facilitation by the first author, at the second
      attempt. Of the total, 10 determinants of LBW were finally prioritized. Twenty
      actions to address the 10 selected prioritized determinants were agreed through a
      collective consensus development process. CONCLUSIONS: Lay communities
      successfully identified determinants of LBW and household level actions to
      address these, with relatively simple guidance, when stimulated to initiate the
      relevant process. This capacity should be nurtured and better used in
      interventions to improve LBW.

PMID- 29212533
TI  - Subtracting the sequence bias from partially digested MNase-seq data reveals a
      general contribution of TFIIS to nucleosome positioning.
AB  - BACKGROUND: TFIIS stimulates RNA cleavage by RNA polymerase II and promotes the
      resolution of backtracking events. TFIIS acts in the chromatin context, but its
      contribution to the chromatin landscape has not yet been investigated. Co
      transcriptional chromatin alterations include subtle changes in nucleosome
      positioning, like those expected to be elicited by TFIIS, which are elusive to
      detect. The most popular method to map nucleosomes involves intensive chromatin
      digestion by micrococcal nuclease (MNase). Maps based on these exhaustively
      digested samples miss any MNase-sensitive nucleosomes caused by transcription. In
      contrast, partial digestion approaches preserve such nucleosomes, but introduce
      noise due to MNase sequence preferences. A systematic way of correcting this bias
      for massively parallel sequencing experiments is still missing. RESULTS: To
      investigate the contribution of TFIIS to the chromatin landscape, we developed a
      refined nucleosome-mapping method in Saccharomyces cerevisiae. Based on partial
      MNase digestion and a sequence-bias correction derived from naked DNA cleavage,
      the refined method efficiently mapped nucleosomes in promoter regions rich in
      MNase-sensitive structures. The naked DNA correction was also important for
      mapping gene body nucleosomes, particularly in those genes whose core promoters
      contain a canonical TATA element. With this improved method, we analyzed the
      global nucleosomal changes caused by lack of TFIIS. We detected a general
      increase in nucleosomal fuzziness and more restricted changes in nucleosome
      occupancy, which concentrated in some gene categories. The TATA-containing genes
      were preferentially associated with decreased occupancy in gene bodies, whereas
      the TATA-like genes did so with increased fuzziness. The detected chromatin
      alterations correlated with functional defects in nascent transcription, as
      revealed by genomic run-on experiments. CONCLUSIONS: The combination of partial
      MNase digestion and naked DNA correction of the sequence bias is a precise
      nucleosomal mapping method that does not exclude MNase-sensitive nucleosomes.
      This method is useful for detecting subtle alterations in nucleosome positioning
      produced by lack of TFIIS. Their analysis revealed that TFIIS generally
      contributed to nucleosome positioning in both gene promoters and bodies. The
      independent effect of lack of TFIIS on nucleosome occupancy and fuzziness
      supports the existence of alternative chromatin dynamics during transcription
      elongation.

PMID- 29212535
TI  - Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for
      laryngeal cancer: a case report.
AB  - BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of
      immune complexes and is related to many causes, including medication. To the best
      of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet
      been described in the scientific literature. CASE PRESENTATION: We report a rare
      case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin
      chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with
      larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2
      every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a
      therapeutic schedule. Twelve days after the first chemotherapy administration and
      after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with
      acute onset of palpable purpura in the lower limbs. The patient was hospitalized
      for 10 days, and during this period, he underwent several examinations to rule
      out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed
      leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected
      through direct immunofluorescence. Twenty-five days after cisplatin
      administration, the chemotherapy regimen was changed to carboplatin AUC 5, and
      the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction
      to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and
      clinicians should be aware of this potential effect for better case management
      and diagnosis.

PMID- 29212536
TI  - Towards healthy learning climates in postgraduate medical education: exploring
      the role of hospital-wide education committees.
AB  - BACKGROUND: Postgraduate medical education prepares residents for delivery of
      high quality patient care during training as well as for later practice, which
      makes high quality residency training programs crucial to safeguard patient care.
      Healthy learning climates contribute to high quality postgraduate medical
      education. In several countries, modernization of postgraduate medical education
      has resulted in hospital-wide responsibilities for monitoring learning climates.
      This study investigates the association between the actions undertaken by
      hospital-wide education committees and learning climates in postgraduate medical
      education. METHODS: Research conducted in December 2010 invited 57 chairs of
      hospital-wide education committees to complete a questionnaire on their
      implemented level of quality improvement policies. We merged the survey data from
      21 committees that oversaw training programs and used the Dutch Residency
      Educational Climate Test (D-RECT) instrument in 2012 to measure their training
      programs' learning climate. We used descriptive statistics and linear mixed
      models to analyse associations between the functioning of hospital-wide education
      committees and corresponding learning climates. RESULTS: In total, 812 resident
      evaluations for 99 training programs in 21 teaching hospitals were available for
      analysis. The implementation level of the internal quality management systems as
      adopted by the hospital-wide education committees varied from 1.6 to 2.6 on a 5
      point Likert-scale (ranging from 1 (worst) to 5 (best)). No significant
      associations were found between the functioning of the committees and
      corresponding learning climates. CONCLUSIONS: The contribution of hospital-wide
      committees to creating healthy learning climates is yet to be demonstrated. The
      absence of such an association could be due to the lack of a Plan-Do-Check-Act
      cycle guiding the policy as implemented by the committees and the lack of
      involvement of departmental leadership. Insight into the impact of these
      strategies on learning climates will benefit the quality of postgraduate medical
      education and, hopefully, patient care.

PMID- 29212537
TI  - Association of ARMS2 genotype with response to anti-vascular endothelial growth
      factor treatment in polypoidal choroidal vasculopathy.
AB  - BACKGROUND: To investigate whether genetic risk variants for age-related macular
      degeneration (AMD) are associated with response to intravitreal anti-vascular
      endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV)
      patients. METHODS: This prospective cohort study included 95 treatment-naive
      patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were
      genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes.
      Genotypic association with visual and anatomic outcome measures at 12 months
      after initial treatment, including mean change in best-corrected visual acuity
      (BCVA) and total foveal thickness, visual gain of >= 15 letters, dry status on
      optical coherence tomography (OCT), pigment epithelial detachment (PED)
      regression on OCT, polyp regression on indocyanine green angiography, and
      injection numbers, were investigated using regression models with adjustment for
      non-genetic covariates under additive genetic model. RESULTS: In 81 patients who
      completed 12-month anti-VEGF monotherapy without photodynamic therapy,
      significant pharmacogenetic association was found between ARMS2 rs10490924 and
      PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for
      TG, and 63.6% for GG genotype, showing additive effect of G allele for higher
      chance of PED regression (OR, 2.96; 95% CI, 1.38-6.36; corrected P = 0.043). For
      entire 95 patients, no significant association was found between candidate
      polymorphisms and receiving photodynamic therapy within 12 months. CONCLUSIONS:
      In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic
      response to anti-VEGF, suggesting pharmacogenetic relationship.

PMID- 29212538
TI  - A pilot investigation of audiovisual processing and multisensory integration in
      patients with inherited retinal dystrophies.
AB  - BACKGROUND: In this study, we examined audiovisual (AV) processing in normal and
      visually impaired individuals who exhibit partial loss of vision due to inherited
      retinal dystrophies (IRDs). METHODS: Two groups were analyzed for this pilot
      study: Group 1 was composed of IRD participants: two with autosomal dominant
      retinitis pigmentosa (RP), two with autosomal recessive cone-rod dystrophy
      (CORD), and two with the related complex disorder, Bardet-Biedl syndrome (BBS);
      Group 2 was composed of 15 non-IRD participants (controls). Audiovisual looming
      and receding stimuli (conveying perceptual motion) were used to assess the
      cortical processing and integration of unimodal (A or V) and multimodal (AV)
      sensory cues. Electroencephalography (EEG) was used to simultaneously resolve the
      temporal and spatial characteristics of AV processing and assess differences in
      neural responses between groups. Measurement of AV integration was accomplished
      via quantification of the EEG's spectral power and event-related brain potentials
      (ERPs). RESULTS: Results show that IRD individuals exhibit reduced AV integration
      for concurrent audio and visual (AV) stimuli but increased brain activity during
      the unimodal A (but not V) presentation. This was corroborated in behavioral
      responses, where IRD patients showed slower and less accurate judgments of AV and
      V stimuli but more accurate responses in the A-alone condition. CONCLUSIONS:
      Collectively, our findings imply a neural compensation from auditory sensory
      brain areas due to visual deprivation.

PMID- 29212539
TI  - The relationships between the combination of person- and organization-related
      conditions and patients' perceptions of palliative care quality.
AB  - BACKGROUND: Little is known about the combination of person- and organization-
      related conditions and the relationships with patients' perspectives of care
      quality. Such a combination could contribute knowledge reflecting the complexity
      of clinical practice, and enhance individualized care. The aim was to investigate
      the relationships between the combination of person- and organization-related
      conditions and patients' perceptions of palliative care quality. METHODS: A cross
      sectional study, including 191 patients in the late palliative phase (73%
      response rate) admitted to hospice inpatient care (n = 72), hospice day care (n =
      51), palliative units in nursing homes (n = 30) and home care (n = 38), was
      conducted between November 2013 and December 2014, using the instrument Quality
      from the Patients' Perspective specific to palliative care (QPP-PC). Data were
      analysed, using analysis of covariance, to explore the amount of the variance in
      the dependent variables (QPP-PC) that could be explained by combination of the
      independent variables - Person- and organization-related conditions, - while
      controlling for differences in covariates. RESULTS: Patients scored the care
      received and the subjective importance as moderate to high. The combination of
      person- and organization - related conditions revealed that patients with a high
      sense of coherence, lower age (person - related conditions) and being in a ward
      with access to and availability of physicians (organization-related condition)
      might be associated with significantly higher scores for the quality of care
      received. Gender (women), daily contact with family and friends, and low health
      related quality of life (person-related conditions) might be associated with
      higher scores for subjective importance of the aspects of care quality.
      CONCLUSION: Healthcare personnel, leaders and policy makers need to pay attention
      to person- and organization-related conditions in order to provide person
      centered palliative care of high quality. Further studies from palliative care
      contexts are needed to confirm the findings and to investigate additional
      organizational factors that might influence patients' perceptions of care
      quality.

PMID- 29212540
TI  - Dorsal spine evolution in threespine sticklebacks via a splicing change in MSX2A.
AB  - BACKGROUND: Dorsal spine reduction in threespine sticklebacks (Gasterosteus
      aculeatus) is a classic example of recurrent skeletal evolution in nature.
      Sticklebacks in marine environments typically have long spines that form part of
      their skeletal armor. Many derived freshwater populations have evolved shorter
      spines. Changes in spine length are controlled in part by a quantitative trait
      locus (QTL) previously mapped to chromosome 4, but the causative gene and
      mutations underlying the repeated evolution of this interesting skeletal trait
      have not been identified. RESULTS: Refined mapping of the spine length QTL shows
      that it lies near the MSX2A transcription factor gene. MSX2A is expressed in
      developing spines. In F1 marine * freshwater fish, the marine allele is
      preferentially expressed. Differences in expression can be attributed to splicing
      regulation. Due to the use of an alternative 5 ' splice site within the first
      exon, the freshwater allele produces greater amounts of a shortened, non
      functional transcript and makes less of the full-length transcript. Sequence
      changes in the MSX2A region are shared by many freshwater fish, suggesting that
      repeated evolution occurs by reuse of a spine-reduction variant. To demonstrate
      the effect of full-length MSX2A on spine length, we produced transgenic
      freshwater fish expressing a copy of marine MSX2A. The spines of the transgenic
      fish were significantly longer on average than those of their non-transgenic
      siblings, partially reversing the reduced spine lengths that have evolved in
      freshwater populations. CONCLUSIONS: MSX2A is a major gene underlying dorsal
      spine reduction in freshwater sticklebacks. The gene is linked to a separate gene
      controlling bony plate loss, helping explain the concerted effects of chromosome
      4 on multiple armor-reduction traits. The nature of the molecular changes
      provides an interesting example of morphological evolution occurring not through
      a simple amino acid change, nor through a change only in gene expression levels,
      but through a change in the ratio of splice products encoding both normal and
      truncated proteins.

PMID- 29212541
TI  - Identifying lower limb specific and generalised joint hypermobility in adults:
      validation of the Lower Limb Assessment Score.
AB  - BACKGROUND: The Lower Limb Assessment Score (LLAS) has only been validated in a
      paediatric population. The aim of this study was to validate the use of the LLAS
      in an adult population by: i) evaluating its ability to discriminate between
      different extents of lower limb hypermobility, ii) establishing a cut-off score
      to identify lower limb hypermobility, and iii) determining if the LLAS is able to
      identify Generalised Joint Hypermobility (GJH). METHODS: Participants were
      recruited across three groups representing varying degrees of hypermobility. They
      were assessed using the LLAS, Beighton score and clinical opinion. Pearson's
      correlation coefficient and MANOVA were used to assess between-group differences
      in the LLAS. The cut-off score was determined using median and inter-quartile
      ranges and the Receiver Operator Characteristic Curve. The ability of the LLAS to
      identify GJH was assessed using percent agreement with clinical opinion. RESULTS:
      One hundred twelve participants aged 18-40 years were recruited. The LLAS
      distinguished the control from the likely hypermobile and known hypermobile
      cohorts (both p < 0.001), as well as the likely hypermobile from the known
      hypermobile cohort (p = 0.003). The LLAS cut-off score for identifying lower limb
      hypermobility was >=7/12 with a specificity of 86% and sensitivity of 68%. The
      LLAS accurately identified those with GJH with high percentage agreement compared
      to clinical opinion across all cohorts (69-98%). CONCLUSIONS: The LLAS is a valid
      tool for identifying lower limb specific hypermobility and GJH in adults at a cut
      off score of >=7/12. It demonstrates excellent specificity and moderate
      sensitivity, and discriminates well between extents of hypermobility.

PMID- 29212542
TI  - A framework to find the logic backbone of a biological network.
AB  - BACKGROUND: Cellular behaviors are governed by interaction networks among
      biomolecules, for example gene regulatory and signal transduction networks. An
      often used dynamic modeling framework for these networks, Boolean modeling, can
      obtain their attractors (which correspond to cell types and behaviors) and their
      trajectories from an initial state (e.g. a resting state) to the attractors, for
      example in response to an external signal. The existing methods however do not
      elucidate the causal relationships between distant nodes in the network. RESULTS:
      In this work, we propose a simple logic framework, based on categorizing causal
      relationships as sufficient or necessary, as a complement to Boolean networks. We
      identify and explore the properties of complex subnetworks that are distillable
      into a single logic relationship. We also identify cyclic subnetworks that ensure
      the stabilization of the state of participating nodes regardless of the rest of
      the network. We identify the logic backbone of biomolecular networks, consisting
      of external signals, self-sustaining cyclic subnetworks (stable motifs), and
      output nodes. Furthermore, we use the logic framework to identify crucial nodes
      whose override can drive the system from one steady state to another. We apply
      these techniques to two biological networks: the epithelial-to-mesenchymal
      transition network corresponding to a developmental process exploited in tumor
      invasion, and the network of abscisic acid induced stomatal closure in plants. We
      find interesting subnetworks with logical implications in these networks. Using
      these subgraphs and motifs, we efficiently reduce both networks to succinct
      backbone structures. CONCLUSIONS: The logic representation identifies the causal
      relationships between distant nodes and subnetworks. This knowledge can form the
      basis of network control or used in the reverse engineering of networks.

PMID- 29212543
TI  - Gene gravity-like algorithm for disease gene prediction based on phenotype
      specific network.
AB  - BACKGROUND: Polygenic diseases are usually caused by the dysfunction of multiple
      genes. Unravelling such disease genes is crucial to fully understand the genetic
      landscape of diseases on molecular level. With the advent of 'omic' data era,
      network-based methods have prominently boosted disease gene discovery. However,
      how to make better use of different types of data for the prediction of disease
      genes remains a challenge. RESULTS: In this study, we improved the performance of
      disease gene prediction by integrating the similarity of disease phenotype,
      biological function and network topology. First, for each phenotype, a phenotype
      specific network was specially constructed by mapping phenotype similarity
      information of given phenotype onto the protein-protein interaction (PPI)
      network. Then, we developed a gene gravity-like algorithm, to score candidate
      genes based on not only topological similarity but also functional similarity. We
      tested the proposed network and algorithm by conducting leave-one-out and leave
      10%-out cross validation and compared them with state-of-art algorithms. The
      results showed a preference to phenotype-specific network as well as gene gravity
      like algorithm. At last, we tested the predicting capacity of proposed algorithms
      by test gene set derived from the DisGeNET database. Also, potential disease
      genes of three polygenic diseases, obesity, prostate cancer and lung cancer, were
      predicted by proposed methods. We found that the predicted disease genes are
      highly consistent with literature and database evidence. CONCLUSIONS: The good
      performance of phenotype-specific networks indicates that phenotype similarity
      information has positive effect on the prediction of disease genes. The proposed
      gene gravity-like algorithm outperforms the algorithm of Random Walk with Restart
      (RWR), implicating its predicting capacity by combing topological similarity with
      functional similarity. Our work will give an insight to the discovery of disease
      genes by fusing multiple similarities of genes and diseases.

PMID- 29212545
TI  - A systematic review and meta-analysis of psychological predictors of successful
      assisted reproductive technologies.
AB  - OBJECTIVES: The aim of this systematic review and meta-analysis was to perform an
      updated investigation of the effects of depression and anxiety on pregnancy
      outcomes following assisted reproductive technologies. A bibliographic search was
      performed using PubMed, PsycINFO, Embase, Science Direct databases. Data
      retrieved were analysed using a random effects model to estimate standardised
      mean differences. RESULTS: Of the 22 included studies, 18 investigated
      depression, 15 state anxiety, and seven trait anxiety. Data from 4018 patients
      were included in the meta-analysis. Results indicated that women who achieved
      pregnancy or a live birth reported lower levels of depression pre-treatment than
      those who did not, although the effects were small d = - 0.177 (95% CI - 0.327 to
      - 0.027, z = 2.309, p = 0.021). These results were consistent under different
      methodological conditions and the quality of these observational were graded as
      satisfactory. A similar pattern was seen for state (d = - 0.096, 95% CI - 0.180
      to - 0.012: z = 2.241, p = 0.025) and trait anxiety (d = -  0.188, 95% CI - 0.007
      to 0.356, z = 2.181, p = 0.029). More research is needed to investigate the
      impact of psychological variables on assisted reproductive technologies outcomes
      and moderator influences during assisted reproductive technologies processes.

PMID- 29212544
TI  - Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients
      undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound
      and virtual histology.
AB  - BACKGROUND: Coronary atherosclerosis progresses faster in patients with diabetes
      mellitus (DM) and causes higher morbidity and mortality in such patients compared
      to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque
      phenotype during lipid-lowering therapy in DM versus non-DM patients using
      advanced intracoronary imaging. METHODS: We analyzed data from 61 patients with
      stable angina pectoris included to the PREDICT trial searching for prediction of
      plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin
      daily). Geometrically correct, fully 3-D representation of the vascular wall
      surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue
      characterization was obtained via fusion of two-plane angiography and IVUS-VH.
      Frame-based indices of plaque morphology and virtual histology analyses were
      computed and averaged in 5 mm long baseline/follow-up registered vessel segments
      covering the entire length of the two sequential pullbacks (baseline, 1-year). We
      analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score
      (LAPS). RESULTS: Despite reaching similar levels of LDL cholesterol (DM 2.12 +/-
      0.91 mmol/l, non-DM 1.8 +/- 0.66 mmol/l, p = 0.21), DM patients experienced,
      compared to non-DM ones, higher progression of mean plaque area (0.47 +/- 1.15
      mm2 vs. 0.21 +/- 0.97, p = 0.001), percent atheroma volume (0.7 +/- 2.8% vs. -
      1.4 +/- 2.5%, p = 0.007), increase of LAPS (0.23 +/- 1.66 vs. 0.13 +/- 1.79, p =
      0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque
      phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non
      DM patients reached significant decrease of LDL cholesterol. Plaque changes were
      more pronounced in PIT (pathologic intimal thickening) compared to TCFA with
      increased plaque area in both phenotypes in DM patients. CONCLUSION: Based on
      detailed 3D analysis, we found advanced plaque phenotype and further
      atherosclerosis progression in DM patients despite the same reached levels of
      LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier:
      NCT01773512.

PMID- 29212546
TI  - Electronic Laboratory Medicine ordering with evidence-based Order sets in primary
      care (ELMO study): protocol for a cluster randomised trial.
AB  - BACKGROUND: Laboratory testing is an important clinical act with a valuable role
      in screening, diagnosis, management and monitoring of diseases or therapies.
      However, inappropriate laboratory test ordering is frequent, burdening health
      care spending and negatively influencing quality of care. Inappropriate tests may
      also result in false-positive results and potentially cause excessive downstream
      activities. Clinical decision support systems (CDSSs) have shown promising
      results to influence the test-ordering behaviour of physicians and to improve
      appropriateness. Order sets, a form of CDSS where a limited set of evidence-based
      tests are proposed for a series of indications, integrated in a computerised
      physician order entry (CPOE) have been shown to be effective in reducing the
      volume of ordered laboratory tests but convincing evidence that they influence
      appropriateness is lacking. The aim of this study is to evaluate the effect of
      order sets on the quality and quantity of laboratory test orders by physicians.
      We also aim to evaluate the effect of order sets on diagnostic error and explore
      the effect on downstream or cascade activities. METHODS: We will conduct a
      cluster randomised controlled trial in Belgian primary care practices. The study
      is powered to measure two outcomes. We will primarily measure the influence of
      our CDSS on the appropriateness of laboratory test ordering. Additionally, we
      will also measure the influence on diagnostic error. We will also explore the
      effects of our intervention on cascade activities due to altered results of
      inappropriate tests. DISCUSSION: We have designed a study that should be able to
      demonstrate whether the CDSS aimed at diagnostic testing is not only able to
      influence appropriateness but also safe with respect to diagnostic error. These
      findings will influence a lager, nationwide implementation of this CDSS. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02950142 .

PMID- 29212547
TI  - Restrictive surgical approach to palliate angina in a patient with coronary three
      vessel disease and biventricular metastatic hepatocellular carcinoma.
AB  - BACKGROUND: Metastatic cardiac tumors may cause different symptoms including
      angina, symptoms of heart failure and/or arrhythmia. In patients with concomitant
      coronary artery disease, it may be difficult to distinguish between angina caused
      by metastases to the heart, for example, by stealing perfusion from the coronary
      arteries, and angina caused by coronary stenosis. Identifying the origin of the
      symptoms is, however, essential for designing appropriate surgical strategies.
      CASE PRESENTATION: A 69-year-old male with multifocal recurrence of a
      hepatocellular carcinoma (HCC) presented with increasing ventricular arrhythmia
      and angina several weeks after posterior myocardial infarction and PCI of the RCA
      culprit lesion during which two further lesions present in the distal RCX and a
      posterolateral branch, and a chronically occluded LAD had not been addressed. MRI
      showed a large metastatic tumor infiltrating the walls of both ventricles as well
      as the interventricular septum. His debilitating symptoms were attributed to
      steal phenomena and/or perivascular compression caused by the metastatic tumor
      rather than the remaining coronary lesions, and he was offered a restrictive
      surgical approach consisting of debulking of the metastasis with an option for
      subsequent coronary intervention. The palliative surgical procedure resulted in a
      reduction of the tumor mass by half and sufficiently reduced the patient's
      symptoms so that further coronary intervention was not required. CONCLUSIONS:
      Palliative surgery for metastases to the heart may benefit patients, provided
      that the origin of symptoms is identified correctly. It goes without saying that
      in a palliative setting, surgery should be limited to treating symptoms rather
      than performing extensive procedures addressing, for example, coronary artery or
      valve disease. Interventional cardiac procedures addressing not only CAD but also
      valve disease may supplement palliative tumor surgery.

PMID- 29212548
TI  - Generation of stable PDX derived cell lines using conditional reprogramming.
AB  - Efforts to develop effective cancer therapeutics have been hindered by a lack of
      clinically predictive preclinical models which recapitulate this complex disease.
      Patient derived xenograft (PDX) models have emerged as valuable tools for
      translational research but have several practical limitations including lack of
      sustained growth in vitro. In this study, we utilized Conditional Reprogramming
      (CR) cell technology- a novel cell culture system facilitating the generation of
      stable cultures from patient biopsies- to establish PDX-derived cell lines which
      maintain the characteristics of the parental PDX tumor. Human lung and ovarian
      PDX tumors were successfully propagated using CR technology to create stable
      explant cell lines (CR-PDX). These CR-PDX cell lines maintained parental driver
      mutations and allele frequency without clonal drift. Purified CR-PDX cell lines
      were amenable to high throughput chemosensitivity screening and in vitro genetic
      knockdown studies. Additionally, re-implanted CR-PDX cells proliferated to form
      tumors that retained the growth kinetics, histology, and drug responses of the
      parental PDX tumor. CR technology can be used to generate and expand stable cell
      lines from PDX tumors without compromising fundamental biological properties of
      the model. It offers the ability to expand PDX cells in vitro for subsequent 2D
      screening assays as well as for use in vivo to reduce variability, animal usage
      and study costs. The methods and data detailed here provide a platform to
      generate physiologically relevant and predictive preclinical models to enhance
      drug discovery efforts.

PMID- 29212549
TI  - Hypertriglyceridemia and atherosclerosis.
AB  - Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and
      it has been confirmed that increased low density lipoprotein cholesterol (LDL-C)
      is an independent risk factor for atherosclerosis. Recently, the increasing
      evidence has showed that hypertriglyceridemia is associated with incremental
      ASCVD risk. But the proatherogenic mechanism of triglyceride (TG) remains
      unclear. Therefore, this article focuses on the clinical studies and
      proatherogenic mechanism related to hypertriglyceridemia, in order to provide
      reference for the prevention and treatment of ASCVD.

PMID- 29212550
TI  - A supplemental intravenous amino acid infusion sustains a positive protein
      balance for 24 hours in critically ill patients.
AB  - BACKGROUND: Providing supplemental amino acids to ICU patients during a 3-h
      period results in improved whole-body net protein balance, without an increase in
      amino acid oxidation. The primary objective was to investigate if a 24-h
      intravenous amino acid infusion in critically ill patients has a sustained effect
      on whole-body protein balance as was seen after 3 h. Secondary objectives were
      monitoring of amino acid oxidation rate, urea and free amino acid plasma
      concentrations. METHODS: An infusion of [1-13C]-phenylalanine was added to
      ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed
      intravenous infusions of [ring-2H5]-phenylalanine and [3,3-2H2]-tyrosine were
      used to assess whole-body protein synthesis and breakdown, to calculate net
      protein balance and to assess amino acid oxidation at baseline and at 3 and 24
      hours. An intravenous amino acid infusion was added to nutrition at a rate of 1
      g/kg/day and continued for 24 h. RESULTS: Eight patients were studied. The amino
      acid infusion resulted in improved net protein balance over time, from -1.6 +/-
      7.9 MUmol phe/kg/h at 0 h to 6.0 +/- 8.8 at 3 h and 7.5 +/- 5.1 at 24 h (p =
      0.0016). The sum of free amino acids in plasma increased from 3.1 +/- 0.6 mmol/L
      at 0 h to 3.2 +/- 0.3 at 3 h and 3.6 +/- 0.5 at 24 h (p = 0.038). Amino acid
      oxidation and plasma urea were not altered significantly. CONCLUSION: We
      demonstrated that the improvement in whole-body net protein balance from a
      supplemental intravenous amino acid infusion seen after 3 h was sustained after
      24 h in critically ill patients. TRIAL REGISTRATION: This trial was prospectively
      registered at Australian New Zealand Clinical Trials Registry. ACTRN,
      12615001314516 . Registered on 1 December 2015.

PMID- 29212551
TI  - Extracorporeal membrane oxygenation for life-threatening asthma refractory to
      mechanical ventilation: analysis of the Extracorporeal Life Support Organization
      registry.
AB  - BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in cases of
      near-fatal asthma (NFA) has increased, but the benefits and potential
      complications of this therapy have yet to be fully investigated. METHODS: Cases
      were extracted from the Extracorporeal Life Support Organization Registry between
      March 1992 and March 2016. All patients with a diagnosis of asthma (according to
      the International Classification of Diseases 9th edition), who also received
      ECMO, were extracted. Exclusion criteria included patients who underwent multiple
      courses of ECMO; those who received ECMO for cardiopulmonary resuscitation or
      cardiac dysfunction; and those with another primary diagnosis, such as sepsis. We
      analyzed survival to hospital discharge, complications, and clinical factors
      associated with in-hospital mortality, in patients with severe life-threatening
      NFA requiring ECMO support. RESULTS: In total 272 patients were included. The
      mean time spent on ECMO was 176.4 hours. Ventilator settings, including rate,
      fraction of inspired oxygen (FiO2), peak inspiratory pressure (PIP), and mean
      airway pressure, significantly improved after ECMO initiation (rate
      (breaths/min), 19.0 vs. 11.3, p < 0.001; FiO2 (%), 81.2 vs. 48.8, p < 0.001; PIP
      (cmH2O), 38.2 vs. 25.0, p < 0.001; mean airway pressure (cmH2O): 21.4 vs. 14.2, p
      < 0.001). In particular, driving pressure was significantly decreased after ECMO
      support (29.5 vs. 16.8 cmH2O, p < 0.001). The weaning success rate was 86.7%, and
      the rate of survival to hospital discharge was 83.5%. The total complication rate
      was 65.1%, with hemorrhagic complications being the most common (28.3%). Other
      complications included renal (26.8%), cardiovascular (26.1%), mechanical (24.6%),
      metabolic (22.4%), infection (16.5%), neurologic (4.8%), and limb ischemia
      (2.6%). Of the hemorrhagic complications, cannulation site hemorrhage was the
      most common (13.6%). Using multivariate logistic regression analysis, it was
      found that hemorrhage was associated with increased in-hospital mortality (odds
      ratio, 2.97; 95% confidence interval, 1.07-8.24; p = 0.036). Hemorrhage-induced
      death occurred in four patients (1.5%). The most common reason for death was
      organ failure (37.8%). CONCLUSIONS: ECMO can provide adequate gas exchange and
      prevent lung injury induced by mechanical ventilation, and may be an effective
      bridging strategy to avoid aggressive ventilation in refractory NFA. However,
      careful management is required to avoid complications.

PMID- 29212552
TI  - Validity and reliability of simple measurement device to assess the velocity of
      the barbell during squats.
AB  - OBJECTIVES: The velocity of a barbell can provide important insights on the
      performance of athletes during strength training. The aim of this work was to
      assess the validity and reliably of four simple measurement devices that were
      compared to 3D motion capture measurements during squatting. Nine participants
      were assessed when performing 2 * 5 traditional squats with a weight of 70% of
      the 1 repetition maximum and ballistic squats with a weight of 25 kg.
      Simultaneously, data was recorded from three linear position transducers (T
      FORCE, Tendo Power and GymAware), an accelerometer based system (Myotest) and a
      3D motion capture system (Vicon) as the Gold Standard. Correlations between the
      simple measurement devices and 3D motion capture of the mean and the maximal
      velocity of the barbell, as well as the time to maximal velocity, were
      calculated. RESULTS: The correlations during traditional squats were significant
      and very high (r = 0.932, 0.990, p < 0.01) and significant and moderate to high
      (r = 0.552, 0.860, p < 0.01). The Myotest could only be used during the ballistic
      squats and was less accurate. All the linear position transducers were able to
      assess squat performance, particularly during traditional squats and especially
      in terms of mean velocity and time to maximal velocity.

PMID- 29212553
TI  - Household knowledge and practices concerning malaria and indoor residual spraying
      in an endemic area earmarked for malaria elimination in Iran.
AB  - BACKGROUND: Indoor residual spraying of insecticide (IRS) is a key intervention
      for reducing the burden of malaria infection. Effectiveness and success of this
      strategy are to a considerable extent dependent on knowledge and practice of the
      target community regarding the IRS. Iran has entered the malaria elimination
      phase, and IRS has been considered as the main strategy for malaria vector
      control. Therefore, this study was conducted to determine the household knowledge
      and practices about malaria and IRS in Bashagard County, one of the malaria
      endemic areas in the southeast of Iran. METHODS: A community-based cross
      sectional survey was conducted among 420 households in Bashagard County. The
      participants who were selected using a two-stage randomized cluster sampling
      procedure were subjected to a tested structured questionnaire. During the survey,
      direct observations were made concerning the use of IRS as well as housing
      conditions. The data were coded and analysed using SPSS version 19. RESULTS:
      Knowledge levels about malaria as a disease and the mosquito as its vector were
      high and of equal magnitude (85.5% and 85.4%, respectively), while knowledge
      levels of IRS were even higher (91.6%). The main source of households'
      information about malaria and IRS was primarily community health workers (73.3%).
      Despite positive perceptions towards IRS only 26.7% of respondents had sprayed
      their houses which is lower than the WHO targeted coverage of 80%. Respiratory
      disorders and headache (33.3%), food contamination (24.9%), discolouring of inner
      house walls (17.7%), difficulty in furniture's movement (13.8%), and unpleasant
      odour (10.4%) were the main reasons for IRS refusal. CONCLUSION: There is a
      discrepancy between knowledge about symptoms and the transmission route of
      malaria and control practices related to IRS use. Therefore, IRS campaigns
      accompanied with education for behaviour change should be considered to ensure
      householders' participation and cooperation in the IRS programme. Moreover,
      continuous evaluation and monitoring of IRS as well as conducting more surveys on
      knowledge, attitude, and practices are recommended to improve malaria control
      measures and to identify indicators for effective, successful, and sustainable
      malaria elimination programme.

PMID- 29212554
TI  - Benefits of a mentoring support program for individuals with an eating disorder:
      a proof of concept pilot program.
AB  - OBJECTIVE: The aim of this proof-of-concept pilot study was to assess the
      usefulness of a mentoring support program with a goal to improve hope for
      recovery in people with an eating disorder. RESULTS: Significant improvements (p
      <= 0.05) in hope for recovery were found for the mentees in the following
      domains: social relationships (p = 0.027), romantic relationships (p = 0.032),
      family life (p = 0.047), work (0.003) and overall scores (p = 0.003). There were
      no significant findings for any of the areas for the mentors. Despite this,
      mentoring programs that focus on improving hope may provide a valuable adjunct
      support for those in treatment for an eating disorder.

PMID- 29212555
TI  - Study partners should be required in preclinical Alzheimer's disease trials.
AB  - BACKGROUND: In an effort to intervene earlier in Alzheimer's disease (AD),
      clinical trials are testing promising candidate therapies in preclinical disease.
      Preclinical AD trial participants are cognitively normal, functionally
      independent, and autonomous decision-makers. Yet, like AD dementia trials,
      preclinical trials require dual enrollment of a participant and a knowledgeable
      informant, or study partner. MAIN TEXT: The requirement of dyadic enrollment is a
      barrier to recruitment and may present unique ethical challenges. Despite these
      limitations, the requirement should continue. Study partners may be essential to
      ensure participant safety and wellbeing, including overcoming distress related to
      biomarker disclosure and minimizing risk for catastrophic reactions and suicide.
      The requirement may maximize participant retention and ensure data integrity,
      including that study partners are the source of data that will ultimately
      instruct whether a new treatment has a clinical benefit and meaningful impact on
      the population health burden associated with AD. Finally, study partners are
      needed to ensure the scientific and clinical value of trials. CONCLUSIONS:
      Preclinical AD will represent a new model of care, in which persons with no
      symptoms are informed of probable cognitive decline and eventual dementia. The
      rationale for early diagnosis in symptomatic AD is equally applicable in
      preclinical AD-to minimize risk, maximize quality of life, and ensure optimal
      planning and communication. Family members and other sources of support will
      likely be essential to the goals of this new model of care for preclinical AD
      patients and trials must instruct this clinical practice.

PMID- 29212558
TI  - Effects of low-fat compared with high-fat diet on cardiometabolic indicators in
      people with overweight and obesity without overt metabolic disturbance: a
      systematic review and meta-analysis of randomised controlled trials.
AB  - Randomised controlled trials comparing low- v. high-fat diets on cardiometabolic
      risk factors in people with overweight or obesity have shown inconsistent
      results, which may be due to the mixed metabolic status of people with excess
      adiposity. The role of dietary fat manipulation in modifying cardiometabolic
      indicators in people with overweight or obese without metabolic disturbance is
      unclear. Thus, meta-analysis was conducted to compare low- v. high-fat diets on
      cardiometabolic indicators in people who are overweight or obese without
      metabolic disturbance in the present study. Databases were searched until October
      2016. The pooled effects of outcomes with heterogeneity were calculated with a
      random-effects model, heterogeneities were analysed by subgroup and meta
      regression. As a result, twenty studies with 2106 participants were included in
      the meta-analysis. Total cholesterol and LDL-cholesterol levels were lower
      following low-fat diets compared with high-fat diets: weighted mean difference
      (WMD) was -7.05 mg/dl (-0.18 mmol/l; 95 % CI -11.30, -2.80; P=0.001) and -4.41
      mg/dl (-0.11 mmol/l; 95 % CI -7.81, -1.00; P=0.011), respectively. Conversely,
      significant higher level of TAG (WMD: 11.68 mg/dl (0.13 mmol/l), 95 % CI 5.90,
      17.45; P<0.001) and lower level of HDL-cholesterol (WMD: -2.57 mg/dl (-0.07
      mmol/l); 95 % CI -3.85, -1.28; P<0.001) were found following low-fat diets
      compared with high-fat diets. In conclusion, dietary fat manipulation has a
      significant influence on blood lipid levels in people with overweight or obesity
      without metabolic disturbances.

PMID- 29212556
TI  - Clinical interval and diagnostic characteristics in a cohort of bladder cancer
      patients in Spain: a multicenter observational study.
AB  - OBJECTIVE: We performed a cohort study in seven hospitals in Spain to determine
      the clinical characteristics of incident patients with bladder cancer, the
      diagnostic process, and the conditions that might affect health care interval
      times. RESULTS: 314 patients with bladder cancer were included, 70.3 (Standard
      Deviation [SD] 11.2) years old and 85.0% male. Clinical stage was T1 in 45.9% of
      patients. The median interval time between first consultation and diagnosis was
      of 104.0 days (Inter quartile range [IQR]:112.0; range from 0 to 986), being
      shorter for those patients who attended a hospital for their first consultation.
      The median interval time between diagnosis and first treatment was of 0.0 days
      (IQR: 0.0; range from 0 to 366), being longer when the patient had a pathologic
      tumor stage >= T2a.

PMID- 29212557
TI  - Preconditioning of murine mesenchymal stem cells synergistically enhanced
      immunomodulation and osteogenesis.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are capable of immunomodulation and
      tissue regeneration, highlighting their potential translational application for
      treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated
      by proinflammatory cytokines and pathogen-associated molecular patterns such as
      lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon
      gamma (IFN-gamma) and the proinflammatory cytokine tumor necrosis factor alpha
      (TNF-alpha) synergistically suppressed T-cell activation. METHODS: In the current
      study, we developed a novel preconditioning strategy for MSCs using LPS plus TNF
      alpha to optimize the immunomodulating ability of MSCs on macrophage
      polarization. RESULTS: Preconditioned MSCs enhanced anti-inflammatory M2
      macrophage marker expression (Arginase 1 and CD206) and decreased inflammatory M1
      macrophage marker (TNF-alpha/IL-1Ra) expression using an in-vitro coculture
      model. Immunomodulation of MSCs on macrophages was significantly increased
      compared to the combination of IFN-gamma plus TNF-alpha or single treatment
      controls. Increased osteogenic differentiation including alkaline phosphate
      activity and matrix mineralization was only observed in the LPS plus TNF-alpha
      preconditioned MSCs. Mechanistic studies showed that increased prostaglandin E2
      (PGE2) production was associated with enhanced Arginase 1 expression. Selective
      cyclooxygenase-2 inhibition by Celecoxib decreased PGE2 production and Arginase 1
      expression in cocultured macrophages. CONCLUSIONS: The novel preconditioned MSCs
      have increased immunomodulation and bone regeneration potential and could be
      applied to the treatment of inflammatory bone disorders including periprosthetic
      osteolysis, fracture healing/nonunions, and osteonecrosis.

PMID- 29212559
TI  - The body remembers: Adolescent conflict struggles predict adult interleukin-6
      levels.
AB  - Struggles managing conflict and hostility in adolescent social relationships were
      examined as long-term predictors of immune-mediated inflammation in adulthood
      that has been linked to long-term health outcomes. Circulating levels of
      interleukin-6 (IL-6), a marker of immune system dysfunction when chronically
      elevated, were assessed at age 28 in a community sample of 127 individuals
      followed via multiple methods and reporters from ages 13 to 28. Adult serum IL-6
      levels were predicted across periods as long as 15 years by adolescents'
      inability to defuse peer aggression and poor peer-rated conflict resolution
      skills, and by independently observed romantic partner hostility in late
      adolescence. Adult relationship difficulties also predicted higher IL-6 levels
      but did not mediate predictions from adolescent-era conflict struggles.
      Predictions were also not mediated by adult trait hostility or aggressive
      behavior, suggesting the unique role of struggles with conflict and hostility
      from others during adolescence. The implications for understanding the import of
      adolescent peer relationships for life span physical health outcomes are
      considered.

PMID- 29212561
TI  - Crosstalk between Entamoeba histolytica and the human intestinal tract during
      amoebiasis.
AB  - The protozoan parasite Entamoeba histolytica is the microbial agent of amoebiasis
      - an infection that is endemic worldwide and is associated with high morbidity
      and mortality rates. As the disease develops, virulent E. histolytica deplete the
      mucus layer, interact with the intestinal epithelium, and then degrade the
      colonic mucosa and disrupt the extracellular matrix (ECM). Our research
      demonstrated that virulent parasites with an invasive phenotype display rapid,
      highly specific changes in their transcriptome (notably for essential factors
      involved in carbohydrate metabolism and the processing of glycosylated residues).
      Moreover, combined activation of parasite and host lytic enzymes leads to the
      destruction of the intestinal parenchyma. Together, these enzymes degrade the
      mucus layer and the ECM, and trigger the inflammatory response essential to the
      development of amoebiasis.

PMID- 29212560
TI  - Concurrent benzodiazepine use in older adults treated with antidepressants in
      Asia.
AB  - BACKGROUND: Little is known about the combined use of benzodiazepines and
      antidepressants in older psychiatric patients. This study examined the
      prescription pattern of concurrent benzodiazepines in older adults treated with
      antidepressants in Asia, and explored its demographic and clinical correlates.
      METHODS: The data of 955 older adults with any type of psychiatric disorders were
      extracted from the database of the Research on Asian Psychotropic Prescription
      Patterns for Antidepressants (REAP-AD) project. Demographic and clinical
      characteristics were recorded using a standardized protocol and data collection
      procedure. Both univariate and multiple logistic regression analyses were
      performed. RESULTS: The proportion of benzodiazepine and antidepressant
      combination in this cohort was 44.3%. Multiple logistic regression analysis
      revealed that higher doses of antidepressants, younger age (<65 years),
      inpatients, public hospital, major comorbid medical conditions, antidepressant
      types, and country/territory were significantly associated with more frequent co
      prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of
      the older adults treated with antidepressants in Asia are prescribed concurrent
      benzodiazepines. Given the potentially adverse effects of benzodiazepines, the
      rationale of benzodiazepines and antidepressants co-prescription needs to be
      revisited.

PMID- 29212562
TI  - A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in
      treatment of myalgic encephalomyelitis/chronic fatigue syndrome.
AB  - OBJECTIVE: The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown
      promising effects on mental fatigue after stroke and traumatic brain injury. This
      study investigated the safety and effectiveness of (-)-OSU6162 in patients with
      myalgic encephalomyelitis/chronic fatigue syndrome. METHODS: A total of 62
      patients were randomly assigned to placebo or (-)-OSU6162. Primary outcomes were
      assessment on the mental fatigue scale (MFS) and the clinical global impression
      of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue
      scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale
      and neuropsychological tests. Assessments were performed at baseline, after 1 and
      2 weeks of treatment and at follow-up after 6 weeks. RESULTS: MFS and CGI-C
      showed significant improvements for both treatment groups after treatment but not
      at follow-up; a similar pattern was seen for FF and BDI. However, significant
      differences between groups could not be demonstrated. On the other hand,
      correlation analyses showed a significant correlation between (-)-OSU6162
      concentration and change in MFS, FF, and BDI score within the concentration
      interval 0.1-0.7 uM. Exploratory subgroup analyses showed a larger treatment
      effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on
      antidepressant therapy compared to those without antidepressant treatment.
      CONCLUSION: (-)-OSU6162 was found to be safe and well tolerated. When analysing
      the entire material (-)-OSU6162 was not found to differ significantly from
      placebo in alleviating fatigue in ME patients but was superior to placebo in
      counteracting fatigue in a subgroup of ME patients who received concomitant
      pharmacological treatment for depression.

PMID- 29212563
TI  - Clinically relevant and simple immune system measure is related to symptom burden
      in bipolar disorder.
AB  - OBJECTIVE: Immunological theories, particularly the sickness syndrome theory, may
      explain psychopathology in mood disorders. However, no clinical trials have
      investigated the association between overall immune system markers with a wide
      range of specific symptoms including potential gender differences. METHODS: We
      included two similar clinical trials, the lithium treatment moderate-dose use
      study and clinical and health outcomes initiatives in comparative effectiveness
      for bipolar disorder study, enrolling 765 participants with bipolar disorder. At
      study entry, white blood cell (WBC) count was measured and psychopathology
      assessed with the Montgomery and Aasberg depression rating scale (MADRS). We
      performed analysis of variance and linear regression analyses to investigate the
      relationship between the deviation from the median WBC, and multinomial
      regression analysis between different WBC levels. All analyses were performed
      gender-specific and adjusted for age, body mass index, smoking, race, and somatic
      diseases. RESULTS: The overall MADRS score increased significantly for each
      1.0*109/l deviation from the median WBC among 322 men (coefficient=1.10; 95%
      CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19
      1.31; p=0.14). Among men, WBC deviations were associated with increased severity
      of sadness, inner tension, reduced sleep, reduced appetite, concentration
      difficulties, inability to feel, and suicidal thoughts. Among women, WBC
      deviations were associated with increased severity of reduced appetite,
      concentration difficulties, lassitude, inability to feel, and pessimistic
      thoughts. Both higher and lower WBC levels were associated with increased
      severity of several specific symptoms. CONCLUSION: Immune system alterations were
      associated with increased severity of specific mood symptoms, particularly among
      men. Our results support the sickness syndrome theory, but furthermore emphasise
      the relevance to study immune suppression in bipolar disorder. Due to the
      explorative nature and cross-sectional design, future studies need to confirm
      these findings.

PMID- 29212565
TI  - Improving quality of referral letters from primary to secondary care: a
      literature review and discussion paper.
AB  - BACKGROUND: Referral letters sent from primary to secondary or tertiary care are
      a crucial element in the continuity of patient information transfer.
      Internationally, the need for improvement in this area has been recognised. This
      aim of this study is to review the current literature pertaining to interventions
      that are designed to improve referral letter quality. METHODS: A search strategy
      designed following a Problem, Intervention, Comparator, Outcome model was used to
      explore the PubMed and EMBASE databases for relevant literature. Inclusion and
      exclusion criteria were established and bibliographies were screened for relevant
      resources. RESULTS: A total of 18 publications were included in this study. Four
      types of interventions were described: electronic referrals were shown to have
      several advantages over paper referrals but were also found to impose new
      barriers; peer feedback increases letter quality and can decrease 'inappropriate
      referrals' by up to 50%; templates increase documentation and awareness of risk
      factors; mixed interventions combining different intervention types provide
      tangible improvements in content and appropriateness. CONCLUSION: Several
      methodological considerations were identified in the studies reviewed but our
      analysis demonstrates that a combination of interventions, introduced as part of
      a joint package and involving peer feedback can improve.

PMID- 29212566
TI  - Segmentation Approach Towards Phase-Contrast Microscopic Images of Activated
      Sludge to Monitor the Wastewater Treatment.
AB  - Image processing and analysis is an effective tool for monitoring and fault
      diagnosis of activated sludge (AS) wastewater treatment plants. The AS image
      comprise of flocs (microbial aggregates) and filamentous bacteria. In this paper,
      nine different approaches are proposed for image segmentation of phase-contrast
      microscopic (PCM) images of AS samples. The proposed strategies are assessed for
      their effectiveness from the perspective of microscopic artifacts associated with
      PCM. The first approach uses an algorithm that is based on the idea that
      different color space representation of images other than red-green-blue may have
      better contrast. The second uses an edge detection approach. The third strategy,
      employs a clustering algorithm for the segmentation and the fourth applies local
      adaptive thresholding. The fifth technique is based on texture-based segmentation
      and the sixth uses watershed algorithm. The seventh adopts a split-and-merge
      approach. The eighth employs Kittler's thresholding. Finally, the ninth uses a
      top-hat and bottom-hat filtering-based technique. The approaches are assessed,
      and analyzed critically with reference to the artifacts of PCM. Gold
      approximations of ground truth images are prepared to assess the segmentations.
      Overall, the edge detection-based approach exhibits the best results in terms of
      accuracy, and the texture-based algorithm in terms of false negative ratio. The
      respective scenarios are explained for suitability of edge detection and texture
      based algorithms.

PMID- 29212567
TI  - The Quebec emergency department guide: A cross-sectional study to evaluate its
      use, perceived usefulness, and implementation in rural emergency departments.
AB  - OBJECTIVES: The Quebec Emergency Department Management Guide (QEDMG) is a unique
      document with 78 recommendations designed to improve the organization of
      emergency departments (EDs) in the province of Quebec. However, no study has
      examined how this guide is perceived or used by rural health care management.
      METHODS: We invited all directors of professional services (DPS), directors of
      nursing services (DNS), head nurses (HN), and emergency department directors
      (EDD) working in Quebec's rural hospitals to complete an online survey (144
      questions). Simple frequency analyses (percentage [%] and 95% confidence
      interval) were conducted to establish general familiarity and use of the QEDMG,
      as well as perceived usefulness and implementation of its recommendations.
      RESULTS: Seventy-three percent (19/26) of Quebec's rural EDs participated in the
      study. A total of 82% (62/76) of the targeted stakeholders participated. Sixty
      one percent of respondents reported being "moderately or a lot" familiar with the
      QEDMG, whereas 77% reported "almost never or sometimes" refer to this guide.
      Physician management (DPS, EDD) were more likely than nursing management (DNS and
      especially HN) to report "not at all" or "little" familiarity on use of the
      guide. Finally, 98% of the QEDMG recommendations were considered useful.
      CONCLUSIONS: Although the QEDMG is considered a useful guide for rural EDs, it is
      not optimally known or used in rural EDs, especially by physician management.
      Stakeholders should consider these findings before implementing the revised
      versions of the QEDMG.

PMID- 29212564
TI  - Nurturant-involved parenting and adolescent substance use: Examining an
      internalizing pathway through adolescent social anxiety symptoms and substance
      refusal efficacy.
AB  - Research has clearly established the important role of parents in preventing
      substance use among early adolescents. Much of this work has focused on deviance
      (e.g., antisocial behavior, delinquency, and oppositional behavior) as a central
      pathway linking parenting behaviors and early adolescent substance use. This
      study proposed an alternative pathway; using a four-wave longitudinal design, we
      examined whether nurturant-involved parenting (Fall sixth grade) was inversely
      associated with adolescent drunkenness, marijuana use, and cigarette use (eighth
      grade) through social anxiety symptoms (Spring sixth grade) and subsequent
      decreases in substance refusal efficacy (seventh grade). Nurturant-involved
      parenting is characterized by warmth, supportiveness, low hostility, and low
      rejection. Analyses were conducted with a sample of 687 two-parent families.
      Results indicated that adolescents who were in families where fathers exhibited
      lower levels of nurturant-involved parenting experienced subsequent increases in
      social anxiety symptoms and decreased efficacy to refuse substances, which in
      turn was related to more frequent drunkenness, cigarette use, and marijuana use.
      Indirect effects are discussed. Findings were not substantiated for mothers'
      parenting. Adolescent gender did not moderate associations. The results highlight
      an additional pathway through which parenting influences youth substance use and
      links social anxiety symptoms to reduced substance refusal efficacy.

PMID- 29212568
TI  - Decomposing environmental unpredictability in forecasting adolescent and young
      adult development: A two-sample study.
AB  - To illuminate which features of an unpredictable environment early in life best
      forecast adolescent and adult functioning, data from two longitudinal studies
      were examined. After decomposing a composite unpredictability construct found to
      predict later development, results of both studies revealed that paternal
      transitions predicted outcomes more consistently and strongly than did
      residential or occupational changes across the first 5 years of a child's life.
      These results derive from analyses of the NICHD Study of Early Child Care and
      Youth Development, which included diverse families from 10 different sites in the
      United States, and from the Minnesota Longitudinal Study of Risk and Adaptation,
      whose participants came from one site, were disproportionately economically
      disadvantaged, and were enrolled 15 years earlier than the NICHD Study sample.
      The finding that results from both studies are consistent with evolutionary, life
      history thinking regarding the importance of males in children's lives makes this
      general, cross-study replication noteworthy.

PMID- 29212569
TI  - The effect of strategic memory training in older adults: who benefits most?
AB  - : ABSTRACTBackground:Previous research has suggested that there is a degree of
      variability among older adults' response to memory training, such that some
      individuals benefit more than others. The aim of the present study was to
      identify the profile of older adults who were likely to benefit most from a
      strategic memory training program that has previously proved to be effective in
      improving memory in healthy older adults. METHOD: In total, 44 older adults (60
      83 years) participated in a strategic memory training. We examined memory
      training benefits by measuring changes in memory practiced (word list learning)
      and non-practiced tasks (grocery list and associative learning). In addition, a
      battery of cognitive measures was administered in order to assess crystallized
      and fluid abilities, short-term memory, working memory, and processing speed.
      RESULTS: Results confirmed the efficacy of the training in improving performance
      in both practiced and non-practiced memory tasks. For the practiced memory tasks,
      results showed that memory baseline performance and crystallized ability
      predicted training gains. For the non-practiced memory tasks, analyses showed
      that memory baseline performance was a significant predictor of gain in the
      grocery list learning task. For the associative learning task, the significant
      predictors were memory baseline performance, processing speed, and marginally the
      age. CONCLUSIONS: Our results indicate that older adults with a higher baseline
      memory capacity and with more efficient cognitive resources were those who tended
      to benefit most from the training. The present study provides new avenues in
      designing personalized intervention according to the older adults' cognitive
      profile.

PMID- 29212570
TI  - 'Teaching Me to Parent Myself': The Feasibility of an In-Patient Group Schema
      Therapy Programme for Complex Trauma.
AB  - BACKGROUND: Group schema therapy is an emerging treatment for personality and
      other psychiatric disorders. It may be particularly suited to individuals with
      complex trauma given that early abuse is likely to create maladaptive schemas.
      AIMS: This pilot study explored the feasibility and effectiveness of a 4-week in
      patient group schema therapy programme for adults with complex trauma in a
      psychiatric hospital setting. METHOD: Thirty-six participants with complex trauma
      syndrome participated in this open trial. Treatment consisted of 60 hours of
      group schema therapy and 4 hours of individual schema therapy administered over 4
      weeks. Feasibility measures included drop-out rates, qualitative interviews with
      participants to determine programme acceptability and measures of psychiatric
      symptoms, self-esteem, quality of life and schema modes pre-, post- and 3 months
      following the intervention. RESULTS: Drop-out rate for the 4-week program was
      11%. Thematic analysis of interview transcripts revealed four major themes:
      connection, mode language explained emotional states, identifying the origin of
      the problem and the emotional activation of the programme. Measures of
      psychiatric symptoms, self-esteem and quality of life showed improvement post
      treatment and at 3 months post-treatment. There was a reduction in most
      maladaptive schema modes pre-/post-treatment. CONCLUSIONS: A group schema therapy
      approach for complex trauma is feasible and demonstrates positive effects on
      psychiatric symptoms and maladaptive schemas.

PMID- 29212571
TI  - Expression of Homeobox Gene HLX and its Downstream Target Genes are Altered in
      Placentae From Discordant Twin Pregnancies.
AB  - A discordant twin gestation, in which one fetus is significantly growth
      restricted, compared to the other normal twin, is a unique model that can be used
      to elucidate the mechanism(s) by which the intrauterine environment affects fetal
      growth. In many model systems, placental transcription factor genes regulate
      fetal growth. Transcription factors regulate growth through their activation or
      repression of downstream target genes that mediate important cell functions. The
      objective of this study was to determine the expression of the placental HLX
      homeobox gene transcription factor and its downstream target genes in dizygotic
      twins with growth discordance. In this cross-sectional study, HLX and its
      downstream target genes' retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C)
      expression levels were determined in placentae obtained from dichorionic
      diamniotic twin pregnancies (n = 23) where one of the twins was growth
      restricted. Fetal growth restriction (FGR) was defined as small for gestational
      age with abnormal umbilical artery Doppler indices when compared with the normal
      control co-twin. Homeobox gene HLX expression was significantly decreased at both
      the mRNA and protein levels in FGR twin placentae compared with the normal
      control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were
      also significantly decreased and increased, respectively, at both the mRNA and
      protein levels in FGR twin placentae compared with normal control co-twin
      placentae (p < .05). Together, these observations suggest an important
      association between HLX transcription factor expression and abnormal human
      placental development in discordant twin pregnancies.

PMID- 29212572
TI  - Aberrant lncRNA Expression in Multiple Myeloma.
AB  - Multiple myeloma (MM), a type of malignant tumor, is characterized by dysplasia
      of clonal plasma cells in the bone marrow. People with MM will have damaged
      organs or tissues due to secretion of large amounts of monoclonal immunoglobulin
      or fragments (M protein). Despite improved survivability by novel treatment
      strategies over the last decade, MM is still incurable by current therapies. Long
      noncoding RNAs (lncRNAs), with length of more than 200 nucleotides, have been
      reported to act as important regulators in many diseases, including MM. Recent
      studies have reported aberrant lncRNA expression in MM; these dysregulated
      lncRNAs can play oncogenic and/or tumor-suppressive roles in the development and
      progression of MM. In this article, we present a general overview on the role of
      lncRNAs in MM pathogenesis and discuss their potential as prognostic biomarkers
      and targets for treatment.

PMID- 29212573
TI  - Knockdown of NF-kappaB1 by shRNA Inhibits the Growth of Renal Cell Carcinoma In
      Vitro and In Vivo.
AB  - Renal cell carcinoma (RCC) accounts for approximately 2%-3% of human malignancies
      and is the most aggressive among urologic tumors. Biological heterogeneity, drug
      resistance, and chemotherapy side effects are the biggest obstacles to the
      effective treatment of RCC. The NF-kappaB transcription factor is one of several
      molecules identified to be responsible for the aggressive phenotype of this
      tumor. In the past decade, several studies have demonstrated the activation of NF
      kappaB in RCC, and many have implicated NF-kappaB1 (p50) as an important molecule
      in tumor progression and metastasis. In the present study, a lentivirus was used
      to deliver shRNA targeting NF-kappaB1 into mouse RCC (Renca) cells. It was
      determined that the knockdown of the NF-kappaB1 gene led to a reduction in cell
      proliferation and late apoptosis/necrosis in vitro. Flow cytometry analysis
      demonstrated G2/M arrest in the cells. In addition, immunoblotting analysis
      revealed a significant increase in cyclin B1 and Bax. In vivo experiments showed
      that Renca-shRNA-NF-kappaB1 cells have significantly diminished tumorigenicity.
      Moreover, immunohistochemical analysis revealed an increase in necrotic areas of
      Renca-shRNA-NF-kappaB1 tumors. Thus, this study indicates that downregulation of
      NF-kappaB1 can suppress RCC tumorigenesis by inducing late apoptosis/necrosis.
      Therefore, NF-kappaB1 may be a potential therapeutic target for RCC.

PMID- 29212574
TI  - Overexpression of Long Noncoding RNA PTENP1 Inhibits Cell Proliferation and
      Migration via Suppression of miR-19b in Breast Cancer Cells.
AB  - This study aimed to investigate the effect of long noncoding RNA PTENP1 in the
      development of breast cancer (BC). Quantitative real-time PCR was utilized to
      determine the expression of PTENP1 in tissues and cell lines. pcDNA3.1 and shRNA
      were used to over- and low-express PTENP1 in BC cell lines, and miR-19b mimic and
      inhibitor were utilized to over- and low-express miR-19b. Then the abilities of
      cell survival, apoptosis, migration, and invasion were assessed in BC cells with
      different expression levels of PTENP1 and miR-19b. The expression of PTENP1 was
      significantly downregulated in both BC tissues and cell lines. Overexpressed
      PTENP1 could significantly increase cell survival, colony forming, migration, and
      invasion but decrease apoptosis in BC cell lines. However, overexpressed miR-19b
      performed contrary effects compared with PTENP1 on cell survival, colony forming,
      migration, invasion, and apoptosis in BC cell lines. miR-19b can be downregulated
      by PTENP1, and the effect of overexpressed PTENP1 on the PI3k/Akt pathway could
      be aborted by overexpressed miR-19b. PTENP1 performed a negative role in the
      development of BC via downregulating miR-19 probably through the PTEN/PI3K/Akt
      pathway.

PMID- 29212575
TI  - Oct4 Is Crucial for Transdifferentiation of Hepatocytes to Biliary Epithelial
      Cells in an In Vitro Organoid Culture Model.
AB  - Hepatocyte to biliary transdifferentiation has been documented in various models
      of bile duct injury. In this process, mature hepatocytes transform into mature
      biliary epithelial cells by acquiring biliary phenotypic markers. Several
      signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown
      to be involved in the process. However, whether Oct4 is involved in hepatocyte to
      biliary transdifferentiation is unknown. We investigated the role of Oct4 in
      hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture
      system as a model of transdifferentiation. Oct4 was inhibited using adenovirus
      containing Oct4 shRNA. Hepatocyte-specific HNF-4alpha and biliary-specific HNF
      1beta and CK19 expression were assessed to gauge the extent of
      transdifferentiation. Oct4 was induced during hepatocyte to biliary
      transdifferentiation. Oct4 inhibition significantly downregulated the appearance
      of biliary cells from hepatocytes. This was accompanied by a significant
      downregulation of signaling pathways including Notch, Sox9, and Hippo. Our
      findings suggest that Oct4 is crucial for hepatocyte to biliary
      transdifferentiation and maturation and that it acts upstream of Notch, Sox9, and
      Hippo signaling in this model. This finding identifies new signaling through Oct4
      in plasticity between hepatocytes and biliary epithelial cells, which can be
      potentially utilized to identify new strategies in chronic biliary diseases.

PMID- 29212577
TI  - AALAS Publications: Write for All Readers.

PMID- 29212576
TI  - The Effects of Physical Exercise on Fatty Liver Disease.
AB  - The increasing prevalence of obesity has made nonalcoholic fatty liver disease
      (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and
      especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the
      fastest increasing etiology of end-stage liver disease and hepatocellular
      carcinoma. Physical inactivity is related to the severity of fatty liver disease
      irrespective of body weight, supporting the hypothesis that increasing physical
      activity through exercise can improve fatty liver disease. This review summarizes
      the evidence for the effects of physical exercise on NAFLD and NASH. Several
      clinical trials have shown that both aerobic and resistance exercise reduce the
      hepatic fat content. From clinical and basic scientific studies, it is evident
      that exercise affects fatty liver disease through various pathways. Improved
      peripheral insulin resistance reduces the excess delivery of free fatty acids and
      glucose for free fatty acid synthesis to the liver. In the liver, exercise
      increases fatty acid oxidation, decreases fatty acid synthesis, and prevents
      mitochondrial and hepatocellular damage through a reduction of the release of
      damage-associated molecular patterns. In conclusion, physical exercise is a
      proven therapeutic strategy to improve fatty liver disease.

PMID- 29212578
TI  - To Treat or Not to Treat: The Effects of Pain on Experimental Parameters.
AB  - A common dilemma faced by all animal bioethics committees arises when exceptions
      are proposed to the use of analgesics in painful procedures. The committee and
      researcher must weigh the possible confounding effects of including additional
      drugs (analgesics) in their treatment regimen against the moral obligation to
      perform humane research. Often neglected in these considerations are the
      potential confounding effects of unrelieved pain and consistency with pain
      relieving practices in human medicine. In this review, we summarize what is
      currently known regarding the molecular and physiologic effects of pain and
      analgesics in common animal models used across several therapeutic areas. This
      work is intended to help provide guidance and assurance that a comprehensive
      approach has been taken when contemplating how pain relief will be applied in
      animal research protocols.

PMID- 29212579
TI  - Time Course of Vitamin D Depletion and Repletion in Reproductive-age Female
      C57BL/6 Mice.
AB  - The use of animal models in vitamin D deficiency (VDD) research, particularly in
      regard to maternal deficits, has increased dramatically, yet these studies may be
      confounded due to ill-conceived experimental timelines. We conducted 2
      experiments to (1) characterize the time course of VDD induction and repletion
      and (2) explore the long-term consequences of VDD on calcium homeostasis and body
      composition in reproductive-age female mice. Eight-week-old female C57BL/6 mice
      were randomized to receive either a vitamin D sufficient (VDS) or VDD diet; serum
      was collected weekly. At week 4, VDD mice were switched to VDS diet, and serum
      was collected weekly until week 8. Another group of same-age female mice was
      maintained on VDD diet for 40 wk. Body weights and serum were collected every 2
      wk until week 40, when body composition was measured by using echoMRI. Mice did
      not become VDD until week 3 of the VDD diet and, after decreasing slightly at 4
      wk, serum 25-hydroxyvitamin D remained unchanged through 40 wk. Vitamin D
      repletion to 25-hydroxyvitamin D concentrations considered adequate by the
      Institute of Medicine took 2 to 3 wk. Prolonged VDD in mice was marked by
      hypocalcemia and hyperparathyroidism and led to proportional decreases in both
      lean and fat mass. These data provide guidance in the design of studies using
      mice as a maternal VDD model, especially those exploring its effects on the
      developmental origins of health and disease and highlight the importance of
      monitoring and controlling the calciotropic effects of diet-induced VDD. This
      study also shows that prolonged VDD in reproductive-age female C57BL/6 mice
      induces metabolically meaningful changes in absolute, but not relative, body
      composition.

PMID- 29212580
TI  - Mice Housed at Elevated Vivarium Temperatures Display Enhanced T-cell Response
      and Survival to Francisella tularensis.
AB  - The inability to translate findings from studies performed in mouse models to the
      corresponding human condition is well known, especially those involving
      infectious, atherosclerotic, and other inflammatory diseases. We hypothesize that
      mice fail to a mount robust or adequate immune response to infectious agents
      because of physiologic effects of cold stress due to housing temperatures below
      the mouse thermoneutral zone (TNZ). This hypothesis was tested by comparing the
      immune response to the Francisella tularensis live vaccine strain in mice housed
      at a typical vivarium temperature, which is below the TNZ, with that of mice
      housed at a temperature near their TNZ. Mice maintained at 28  degrees C
      displayed elevated antigen-specific T-cell responses compared with mice housed at
      22  degrees C and survived intranasal challenge that was fatal to immunized mice
      at 22  degrees C. These results demonstrate that cold stress due to housing below
      the mouse TNZ results in a blunted immune response and may compromise their
      translational value a models for infectious diseases and vaccine development.

PMID- 29212581
TI  - Cationic Liposome-Oligonucleotide Complex as an Alternative Adjuvant for
      Polyclonal Antibody Production in New Zealand White Rabbits
      (Oryctolaguscuniculus).
AB  - Because of their ideal size and temperament, rabbits are commonly used in
      polyclonal antibody production. Immunostimulatory adjuvants-such as Freund
      complete and incomplete adjuvants as well as various proprietary products-trigger
      a robust immune response, which increases antibody concentrations. However, these
      adjuvants can cause excessive soft tissue reactions, prompting concerns regarding
      animal wellbeing. This study assessed the safety and efficacy of cationic
      liposome- oligonucleotide complexes (CLDC) as an alternative adjuvant to
      conventional adjuvants. On days 0 and 14, 15 female New Zealand white rabbits
      were vaccinated subcutaneously with 15 MUg ovalbumin mixed with either CLDC,
      Freund adjuvant (day 0, complete; day 14, incomplete), or a proprietary adjuvant
      (n = 5 per group). Antibody titers were measured by direct ELISA on days 0, 14,
      and 28. Rabbits were palpated daily for lesion development, and all lesions were
      measured. Rabbits in all groups developed a significant antibody response to
      ovalbumin over 28 d. However, the differences between groups were not
      statistically significant. No rabbits in the CLDC group developed skin lesions,
      whereas 80% of rabbits that received Freund adjuvant and 100% of those that
      received the proprietary product developed skin lesions. This study demonstrates
      that CLDC may be a valuable and effective alternative adjuvant for polyclonal
      antibody production in rabbits-one that avoids the palpable injection-site
      lesions often seen with other adjuvants.

PMID- 29212582
TI  - Benefits of Intraluminal Agarose Stents during End-to-End Intestinal Anastomosis
      in New Zealand White Rabbits.
AB  - In the present study, we evaluated the utility of an intraluminal agarose stent
      (IAS) for end-to-end intestinal anastomoses in rabbits. Female New Zealand white
      rabbits (n = 14) underwent conventional sutured anastomosis (CSA) with or without
      an IAS. IAS were used to maintain the luminal diameter for more rapid and
      accurate suturing, and then was squeezed transluminally to crush it into
      fragments, which passed through the intestines and were eliminated. The rabbits
      were euthanized on postoperative day 21. At necropsy, the anastomoses were
      assessed for adhesion formation, stenosis, and bursting pressure and were
      examined histologically for collagen content and blood vessel formation.
      Anastamosis surgery took less time in the IAS group (15.0 +/- 2.6 min) than in
      the CSA-only group (30.1 +/- 7.9 min). Only 1 postoperative death occurred (in
      the CSA group), and postmortem examination revealed evidence of anastomotic
      leakage. Adhesion formation and stenosis did not differ between groups, but
      bursting pressure, collagen content, and blood vessel formation were all
      significantly increased in the IAS group. IAS may decrease the operative time by
      maintaining a clear surgical field at the anastomotic site. In addition, the use
      of IAS promotes rapid healing and maintains the luminal diameter during end-to
      end intestinal anastomosis.

PMID- 29212583
TI  - Effect of Caloric Restriction on Metabolic Dysfunction of Young Rapacz Familial
      Hypercholesterolemic Swine (Sus scrofa).
AB  - The Rapacz familial hypercholesterolemic (FH) swine model is well-characterized
      and used for studies of both spontaneous and inducible atherosclerosis but has
      not been used for studies of metabolic dysfunction to date. We examined whether
      parameters of metabolic syndrome including weight and adiposity, serum
      cholesterol, and glucoregulatory function could be modulated by restriction of
      caloric intake in the FH swine. Three groups of FH swine (n = 6 per group) were
      fed without restriction (AL), 80% of AL caloric intake, or 60% of AL caloric
      intake for 8.8 +/- 0.5 mo beginning 2 wk after weaning. Caloric intake influenced
      the rate and magnitude of body weight gain and change in adiposity, as determined
      by dual-emission X-ray absorptiometry. At the conclusion of the study, pigs in
      the AL group reached a total least-square mean body weight of 94.2 kg and fat
      mass of 31.1%, whereas those fed 80% AL were 71.6 kg and 24.3% fat, and swine fed
      60% AL were 46.1 kg and 14.1% fat. Serum cholesterol was greater in AL than 60%
      AL pigs at the end of the study. At 10 mo of age, intravenous glucose tolerance
      testing, performed to assess glucoregulatory function, indicated significant
      differences in serum glucose clearance profiles and insulin sensitivity between
      the AL- and 60% AL-fed swine. The AL-fed animals showed almost 5-fold lower
      insulin sensitivity when compared with animals fed 60% AL caloric intake. These
      results highlight the value of the FH swine model to study metabolic dysfunction
      due to changes in caloric intake.

PMID- 29212584
TI  - Horner Syndrome in 2 Pigs (Sus scrofa) after Vascular Grafting of the Carotid
      Artery and Jugular Vein.
AB  - The term Horner syndrome refers to the clinical presentation of
      oculosympathoparesis, comprising miosis, ptosis, and facial anhydrosis. To date,
      there are 2 reports of postoperative Horner syndrome in pigs. In this species the
      cervical sympathetic chain and cranial cervical sympathetic ganglion are
      consistently within the carotid artery sheath. This case study describes the
      sudden onset of Horner syndrome in 2 pigs, from a study cohort of 8, after the
      placement of a vascular graft between the carotid artery and external jugular
      vein. Anesthesia and surgery was uneventful in all the pigs in the study, but 2
      pigs demonstrated clinical signs including ptosis, enophthalmos and prolapse of
      the nictitating membrane immediately after recovery from anesthesia. Horner
      syndrome was diagnosed in light of the clinical signs. These clinical signs
      persisted throughout the 2-mo study period and did not appear to improve or
      deteriorate in that time. Gross examination of the surgery site at the end of the
      study did not reveal an obvious lesion in the carotid artery sheath. The risk of
      Horner syndrome after surgery involving the carotid artery in pigs had not been
      reported prior to this study. Without specific measures to protect the cervical
      sympathetic ganglion during surgery, the incidence of postoperative Horner
      syndrome was 25% in our population of pigs. Although the welfare implications of
      this syndrome are minimal, concerted effort to avoid intraoperative damage to the
      cervical ganglion is essential for future work.

PMID- 29212585
TI  - Clinical Salmonellosis in a Closed Colony of Blood Donor Cats.
AB  - An adult feline blood donor, group-housed in a closed colony with other blood
      donor cats in a laboratory animal facility, developed anorexia, abdominal pain,
      an abdominal mass effect, and hemorrhagic diarrhea. Ultimately Salmonella
      infection was diagnosed. The index cat and 2 additional cats in the closed colony
      had clinical signs consistent with Salmonella and yielded Salmonella serotype
      4,12:i:- in fecal cultures. An extensive search for the source of Salmonella was
      unrewarding. With the implementation of individual housing and additional barrier
      precautions, combined with antibiotic treatment of the index case, all the cats
      survived and subsequently had multiple, negative Salmonella PCR test results.
      This case report highlights the potential for unlikely infections to occur, even
      in a closed colony of research animals, as well as the important role of
      sanitation in the elimination of this enteric pathogen.

PMID- 29212586
TI  - Hypercortisolemia and Depressive-like Behaviors in a Rhesus Macaque (Macaca
      mulatta) Involved in Visual Research.
AB  - A 10-y-old cranially implanted rhesus macaque (Macaca mulatta) involved in visual
      research was presented for dull mentation and weight loss. Physical examination
      revealed alopecia and poor body conditioning, and bloodwork revealed marked
      hypercortisolemia (23 MUg/dL). Differential diagnoses for hypercortisolemia,
      weight loss, and alopecia included Cushing and pseudo-Cushing syndromes. To
      further evaluate hypercortisolemia, we compared the urine cortisol:creatinine
      ratio (UCCR) at baseline and after low-dose dexamethasone suppression (LDDS)
      testing in the presenting animal and healthy naive and implanted working monkeys.
      At baseline, UCCR was 10 times higher in the presenting macaque (118.1 +/- 7.1)
      than in naive animals (12.5 +/- 12.8) and 3 times higher than in healthy
      implanted working macaques (44.4 +/- 6.9); however, levels were suppressed
      similarly by dexamethasone in both the presenting animal and healthy controls. In
      addition, healthy implanted working macaques had significantly higher baseline
      UCCR levels than naive controls, suggesting chronic stress in working animals.
      Abdominal ultrasonography and radiographs of the presenting animal revealed
      marked bilateral adrenal mineralization but no overt adrenal tumor or
      hyperplasia. Overall, these results excluded endogenous Cushing syndrome and
      prompted us to evaluate different causes of pseudo-Cushing syndrome, including
      depression. Using videorecordings to evaluate behavior, we used published
      criteria for macaque models of depression models, including huddling, to make a
      presumptive diagnosis of depression. The macaque was treated with fluoxetine (2
      mg/kg PO daily), provided increased environmental enrichment, and followed over
      time by regular UCCR assessment and videorecordings. The animal improved
      clinically and behaviorally, and UCCR returned to levels observed in working
      implanted macaques (44.4) after 8 wk of treatment. This case highlights the
      potential effect of research-related work on stress and pathologic behaviors in
      macaques and demonstrates the utility of UCCR and LDDS for screening behavioral
      and hypothalamic-pituitary-adrenal abnormalities in these animals.

PMID- 29212587
TI  - Nonreducible Inguinal Hernia Containing the Uterus and Bilateral Adnexa in a
      Rhesus Macaque (Macaca mulatta).
AB  - Inguinal herniation of abdominal viscera is a relatively common condition in both
      humans and domestic animal species. In captive rhesus macaques (Macaca mulatta),
      the highest incidence occurs in overweight, aged males. However, inguinal
      herniation of the uterus with bilateral adnexa is extremely rare in both human
      and veterinary medicine. Here we report a previously undescribed uterine inguinal
      herniation with bilateral adnexa in a 3-y-old female rhesus macaque. Although
      uterine herniation remains a rare condition in rhesus macaques, it should be
      considered as a differential diagnosis in animals with unilateral subcutaneous
      enlargements in the inguinal region.

PMID- 29212588
TI  - Comparisons of vaginal flora patterns among sexual behaviour groups of women:
      implications for the pathogenesis of bacterial vaginosis.
AB  - : Background Bacterial vaginosis (BV) is the most common cause of vaginal
      discharge. The objective was to compare the prevalence of BV by Nugent score
      among African-American women who have sex with women (WSW) and women who have sex
      with women and men (WSWM) compared with an age-matched group of women who have
      sex with men (WSM). Secondary objectives were to correlate low versus high Nugent
      scores with vaginal symptoms among women with BV and to correlate BV diagnosis
      with sexual practices. METHODS: A secondary analysis of clinical and laboratory
      data from African-American WSW (n=73) and WSWM (n=68) participating in the
      Women's Sexual Health Project (August 2011-October 2013) and a 3:1 age-matched
      group of African-American WSM participating in the Longitudinal Study of Vaginal
      Flora (August 1999-February 2002) at a sexually transmissible infection clinic
      (n=423) was performed. RESULTS: Compared with WSM, WSW and WSWM were
      significantly more likely to have BV based on the Nugent score (OR 2.63; 95% CI
      1.55-4.48; P<0.01 and OR 3.67; 95% CI 2.17-6.21; P<0.01 respectively). WSW and
      WSWM with BV were not significantly more likely to have higher Nugent scores than
      WSM with BV. Among women with BV reporting symptoms, there was no significant
      difference in the proportion of women with low-positive versus high-positive
      Nugent scores. Women who participated in receptive vaginal sex (penile or
      digital) within the 30 days preceding study enrolment were significantly more
      likely to have BV (OR 2.50; 95% CI 1.57-3.63; P<0.01). CONCLUSIONS: WSW and WSWM
      were significantly more likely to have BV than WSM. Further analysis of sexual
      practices among sexual behaviour groups of women is needed to determine their
      potential impact on BV rates.

PMID- 29212589
TI  - Time to establish comprehensive long-term monitoring of Australian medical
      graduates?
AB  - We believe that the well being of our medical students (and medical staff
      throughout the continuum of practice) matters too much not to ask, 'How do they
      feel?' Society, and students themselves, have invested too much in their
      education not to query 'How well are they performing in the workplace?'. Our
      accountability to the community demands we ask, 'How are their patients going?'
      This article presents a schema for building long-term monitoring in Australia,
      using linked and reliable data, that will enable these questions to be answered.
      Although the answers will be of interest to many, medical schools will then be
      well placed to alter their programs and processes based on these three domains of
      graduate well being, workplace performance and patient outcomes.

PMID- 29212591
TI  - [Pregnancy after bariatric surgery].
AB  - This is a review of the recommendations regarding pregnancy after bariatric
      surgery from the Danish Society of Obstetrics and Gynaecology. The risk of
      vitamin/mineral deficiencies should be emphasized and checked with blood samples.
      Measurements of fetal growth should be offered at gestational age 28 and 34 as a
      supplement to the standard prenatal procedures because of the increased risk of
      intrauterine growth retardation. Because of persistent obesity there is still an
      increased risk of hypertension and diabetes mellitus. In case of abdominal pain
      internal herniation should be suspected.

PMID- 29212590
TI  - Concordance between monetary and sexual delay discounting in men who have sex
      with men.
AB  - : Background Delay discounting has been found to be associated with numerous
      health-related outcomes, including risky sexual behaviour. To date, it is unclear
      whether delay discounting measured in different domains is associated within
      individuals. The goal of this study was to assess the concordance of monetary and
      sexual delay discounting in men who have sex with men. METHODS: Participants
      completed an online survey, including the Monetary Choice Questionnaire and the
      Sexual Discounting Task. Linear regression models were used to assess the
      association between monetary and sexual discount rates. RESULTS: Sexual discount
      rates did not predict monetary discount rates. There was a substantial amount of
      clustering of sexual discount rates, requiring sexual discounting data to be
      categorised. CONCLUSIONS: Monetary and sexual delay discounting are distinct
      processes that are not necessarily associated within individuals, and monetary
      delay discounting is not an appropriate proxy measure for sexual impulsivity.
      Data from the Sexual Discounting Task are typically rank-transformed for
      analysis. These data suggest that this might be an invalid method of analysis.
      Future studies should investigate the distribution of their data to determine if
      it is appropriate to analyse sexual discounting data as a continuous measure.

PMID- 29212592
TI  - [Immune checkpoint inhibitors and endocrinological side effects].
AB  - Immune checkpoint inhibitors including anti-cytotoxic T-lymphocyte-associated
      antigen-4 and anti-programmed cell death-1 have revolutionized cancer therapy but
      have also induced serious immune-related adverse events including hormonal
      dysfunction. The objective of this review is to characterize the incidence,
      clinical presentation, management and prognosis of the endocrine-related adverse
      events including hypophysitis, thyroid dysfunction and diabetes mellitus.
      Combination therapy is associated with an increased risk of adverse events. We
      recommend close monitoring of the hormone levels and glycaemic status during and
      a year after treatment.

PMID- 29212593
TI  - [Methylene blue against refractory hypotension].
AB  - In this case report we describe a 62-year-old man, intoxicated with losartan, an
      angiotensin-II receptor antagonist. The patient presented with a systolic blood
      pressure of 60 mmHg, metabolic acidosis, and hyperglycaemia. His condition
      worsened within the first hour of arrival despite infusion of four litres of
      saline, epinephrine, norepinephrine, and vasopressin as well as insulin and
      antibiotics. Intravenous methylene blue 75 mg was infused over five minutes.
      Within 30 minutes his systolic pressure increased to 100 mmHg, and the infusion
      of epinephrine could be reduced four hours later.

PMID- 29212594
TI  - [False positive troponin I due to heterophile antibodies].
AB  - The troponin I (TnI) level is essential in the diagnosis of acute myocardial
      infarction, but may be elevated by other cardial and non-cardial causes. We
      report a 32-year-old pregnant woman admitted to hospital because of chest pain
      and dyspnoea. TnI levels were significantly elevated, although there was no
      suspicion of acute coronary syndrome or myocarditis, and supplementary
      diagnostics excluded pulmonary embolism. The TnI level was found to be falsely
      elevated due to immunoassay interference. We stress the need to be aware of the
      possibility of false positive TnI, especially during pregnancy.

PMID- 29212595
TI  - [The human gut microbiota].
AB  - Characterization of the human gut microbiota has caused a paradigm shift in
      modern biomedical research. Maintenance of gut microbiota depends on mutual
      microbe-host interactions, which when disturbed can lead to dysbiosis. Dysbiosis
      has been associated with a variety of autoimmune and metabolic diseases. Studies
      attempt to define bacterial compositional changes, immunity responses or
      molecular patterns associated with specific diseases. The immense research in the
      human microbiota may lead to novel therapeutic strategies by development of
      commensal microbe products in management of diseases.

PMID- 29212596
TI  - Rare cases of Blastobotrys raffinosifermentans as cause of FEV1 decline in two CF
      patients - Whole genome sequencing to exclude transmission.

PMID- 29212597
TI  - Response to: The use of coarsened exact matching to evaluate treatment mode in
      the rib fracture patient.

PMID- 29212598
TI  - The Association Between Vitamin D Deficiency and Metabolic Syndrome in Korean
      Adolescents.
AB  - PURPOSE: This study aimed to analyze the demographic characteristics associated
      with vitamin D deficiency, as well as the association between vitamin D
      deficiency and metabolic syndrome, among Korean adolescents. DESIGN AND METHODS:
      This cross-sectional descriptive study involved 2314 adolescents aged 12-18years.
      Participant data were extracted from the Korean National Health and Nutrition
      Examination Survey conducted between January 2010 and December 2014. A logistic
      regression analysis was performed to analyze the association between vitamin D
      and metabolic syndrome. All analyses were performed using IBM SPSS Statistics 24.
      RESULTS: Among the participants, 78% exhibited vitamin D deficiency and 7.8% had
      metabolic syndrome. The vitamin D deficient and sufficient groups differed
      significantly in terms of age, sex, household income, and self-perceived health
      status. Among the subcomponents of metabolic syndrome, vitamin D deficiency was
      associated with a 2.07-fold higher risk of elevated fasting blood glucose
      (>=100mg/dL). CONCLUSIONS: The association of vitamin D deficiency with an
      increased risk of elevated fasting blood glucose levels suggests that adolescents
      in this population should receive interventions to prevent and manage diabetes.
      In the future, the effects of vitamin D deficiency on chronic health problems,
      including diabetes, should be investigated in adolescents. PRACTICE IMPLICATIONS:
      Adolescents with vitamin D deficiency should be screened for prediabetes, and
      clinicians should be concerned about both the diagnosis and prevention of
      diabetes in this population.

PMID- 29212599
TI  - Depressive Symptoms at Critical Times in Youth With Type 1 Diabetes: Following
      Type 1 Diabetes Diagnosis and Insulin Pump Initiation.
AB  - PURPOSE: Depressive symptoms occur at various times during the life cycle in
      persons with type 1 diabetes. We investigated depressive symptoms prospectively
      in youth with new-onset type 1 diabetes and in those beginning pump therapy.
      METHODS: Youth with type 1 diabetes (N = 96), ages 10-17 years, completed the
      Children's Depression Inventory (CDI) at baseline and at 1, 6, and 12 months
      after diabetes onset or pump start; scores >=13 indicated clinical elevation. The
      change in depressive symptoms and the association between CDI score and
      hemoglobin A1c (HbA1c) level were assessed over 1 year. RESULTS: The new-onset
      group (n = 54) had an HbA1c level of 11.4% +/- 2.5%. The pump group (n = 42) had
      a diabetes duration of 4.1 +/- 3.4 years and an HbA1c level of 8.3% +/- 1.3%. The
      baseline median CDI was 5.0 in both groups and remained low over time (ranging
      from 2.0 to 3.5). Most youth (new onset 72%, pump 81%) scored <13 at all times.
      Those with a CDI score of >=13 in month 1 had 9-fold (95% confidence interval: 3
      28) and 11-fold (95% confidence interval: 3-38) higher risks of CDI score of >=13
      at 6 and 12 months, respectively, than those with a CDI score of <13. New-onset
      youth with a CDI score of >=13 in month 1 had a higher HbA1c level at 6 months
      (8.3% +/- 1.7%) than new-onset youth with a CDI score of <13 (7.2% +/- 1.6%, p =
      .04). CONCLUSIONS: CDI scores over 1 year were similar in the new-onset and pump
      groups. Youth with elevated CDI in the first month after diagnosis or pump start
      were significantly more likely to have a CDI score of >=13 at 6 or 12 months,
      supporting recommendations to screen for depressive symptoms because of
      persistence over time. Those with new-onset diabetes and depressive symptoms in
      the first month had higher HbA1c at 6 months; confirmatory research is needed.

PMID- 29212600
TI  - Two distinct entities: Bladder oversensitivity and detrusor overactivity.

PMID- 29212601
TI  - Autonomic imbalance in sepsis.

PMID- 29212602
TI  - A randomized cross-over study comparing surgical cricothyrotomy techniques by
      combat medics using a synthetic cadaver model.
AB  - OBJECTIVE: Cricothyrotomy is a complex procedure with a high rate of
      complications including failure to cannulate and injury to adjacent anatomy. The
      Control-CricTM System and QuickTrach IITM represent two novel devices designed to
      optimize success and minimize complications with this procedure. This study
      compares these two devices against a standard open surgical technique. METHODS:
      We conducted a randomized crossover study of United States Army combat medics
      using a synthetic cadaver model. Participants performed a surgical cricothyrotomy
      using the standard open surgical technique, Control-CricTM System, and QuickTrach
      IITM device in a random order. The primary outcome was time to successful
      cannulation. The secondary outcome was first-attempt success. We also surveyed
      participants after performing the procedures as to their preferences. RESULTS: Of
      70 enrolled subjects, 65 completed all study procedures. Of those that
      successfully cannulated, the mean times to cannulation were comparable for all
      three methods: standard 51.0s (95% CI 45.2-56.8), QuickTrach IITM 39.8s (95% CI
      31.4-48.2) and the Cric-ControlTM 53.6 (95% CI 45.7-61.4). Cannulation failure
      rates were not significantly different: standard 6.2%, QuickTrach IITM 13.9%,
      Cric-ControlTM 18.5% (p=0.106). First pass success rates were also similar
      (93.4%, 91.1%, 88.7%, respectively, p=0.670). Of respondents completing the post
      study survey, a majority (52.3%) preferred the QuickTrach IITM device.
      CONCLUSIONS: We identified no significant differences between the three
      cricothyrotomy techniques with regards to time to successful cannulation or first
      pass success.

PMID- 29212603
TI  - Floating Aortic Thrombus in a Non-aneurysmal and Non-atherosclerotic Aorta.

PMID- 29212604
TI  - Asymmetrical Arterial Diameters.

PMID- 29212605
TI  - Artificial blastocoel collapse of human blastocysts before vitrification and its
      effect on re-expansion after warming - a prospective observational study using
      time-lapse microscopy.
AB  - Vitrified human blastocysts show varied re-expansion capacity after warming. This
      prospective observational study compared behaviour of artificially collapsed
      blastocysts (study group patients, n = 69) to that of blastocysts that were
      vitrified without artificial collapse (control group patients, n = 72). Warmed
      blastocysts were monitored by time-lapse microscopy and blastocoel re-expansion
      speed and growth patterns compared between study and control groups. These
      parameters were also retrospectively compared between blastocysts that resulted
      in live birth and those that failed. Artificially collapsed blastocysts re
      expanded on average 15.01 um2/min faster than control blastocysts (P = 0.0013).
      Warmed blastocysts expressed four different patterns of blastocoel growth. The
      pattern showing contractions at the end of culture was observed to have a lower
      prevalence in control blastocysts, which coincided with the lower incidence of
      hatching in this group. Re-expansion speed and prevalence of growth patterns were
      comparable between blastocysts that did and did not result in a live birth. This
      was seen in the study and control groups. Despite faster re-expansion and
      different growth patterns of artificially collapsed blastocysts, live birth rate
      did not differ between groups. However, this result should be interpreted with
      caution due to the small sample size and high risk of bias.

PMID- 29212606
TI  - A prospective study of breed differences in the thermal pain sensitivity of dogs.
AB  - OBJECTIVE: To compare the thermal nociceptive thresholds (TNTs) of dogs from
      three working/sport breeds. STUDY DESIGN: Experimental prospective study.
      ANIMALS: Thirty healthy adult dogs of mixed age, sex and reproductive status, 10
      of each of three breeds: Harrier Hound, Greyhound and New Zealand Huntaway.
      METHODS: On one day of each week for 4 weeks, unrestrained dogs were tested six
      times. TNTs were measured using a remotely activated device comprising a thermode
      attached to the thoracic limb, controlled by a microprocessor attached to the
      animal. Latency to exhibit behaviour indicative of nociception after initiation
      of heating and the temperature of the thermode at the point of behavioural
      response were measured. Linear mixed-effects models were fitted to the data, with
      dog included as a random effect, initial thermode temperature as a covariate and
      day, week and breed as fixed effects. RESULTS: Initial thermode temperature
      significantly affected dogs' latency to respond (p < 0.001). Breed had a
      significant effect on both latency to respond and response temperature. Huntaways
      took longer to respond than Harriers or Greyhounds. For example, when the initial
      thermode temperature was 30  degrees C, Huntaways took 39.0 seconds to respond
      compared with 35.8 seconds for Harriers and 36.8 seconds for Greyhounds.
      Huntaways also responded at higher temperatures (mean+/-standard deviation:
      Huntaways 49.7+/-1.3  degrees C, Harriers 48.4+/-1.6  degrees C and Greyhounds
      48.7+/-1.6  degrees C). CONCLUSIONS AND CLINICAL RELEVANCE: Huntaways appeared to
      be less sensitive to thermal pain than the other breeds. Such information could
      be used by researchers and clinicians to better understand the generalizability
      of data gathered from a specific breed to the wider canine population or to
      tailor more effective pharmacological approaches to pain management in dogs.

PMID- 29212607
TI  - When syntax meets action: Brain potential evidence of overlapping between
      language and motor sequencing.
AB  - This study aims to extend the embodied cognition approach to syntactic
      processing. The hypothesis is that the brain resources to plan and perform motor
      sequences are also involved in syntactic processing. To test this hypothesis,
      Event-Related brain Potentials (ERPs) were recorded while participants read
      sentences with embedded relative clauses, judging for their acceptability (half
      of the sentences contained a subject-verb morphosyntactic disagreement). The
      sentences, previously divided into three segments, were self-administered segment
      by-segment in two different sequential manners: linear or non-linear. Linear self
      administration consisted of successively pressing three buttons with three
      consecutive fingers in the right hand, while non-linear self-administration
      implied the substitution of the finger in the middle position by the right foot.
      Our aim was to test whether syntactic processing could be affected by the manner
      the sentences were self-administered. Main results revealed that the ERPs LAN
      component vanished whereas the P600 component increased in response to incorrect
      verbs, for non-linear relative to linear self-administration. The LAN and P600
      components reflect early and late syntactic processing, respectively. Our results
      convey evidence that language syntactic processing and performing non-linguistic
      motor sequences may share resources in the human brain.

PMID- 29212608
TI  - Clinical Islet Transplantation for Adults With Type 1 Diabetes in Canada:
      Referral Patterns and Eligibility Assessment.
AB  - OBJECTIVES: Careful selection for clinical islet transplantation (CIT) is
      required because of limited organ supply and the risks for lifelong
      immunosuppression. However, the indications for this novel treatment may not be
      widely known, and selection criteria continue to evolve. We sought to describe
      the pattern of referrals to our centre and the most common factors determining
      eligibility for CIT. METHODS: We performed a retrospective chart review of all
      applications for CIT received at the University of Alberta between May 2009 and
      April 2012. Demographics and clinical data were abstracted along with the sources
      of referral. Application results and reasons for eligibility or ineligibility
      were determined. For ineligible subjects, the primary reason for ineligibility
      was noted. RESULTS: We received 246 applications (mean age 43; range, 13 to 78
      years; 54% male) from across Canada. The majority (81%) were self-referrals, with
      the remainder coming from specialists (15%) or primary care physicians (4%). Of
      the applicants, 19% were deemed eligible and were accepted for waitlisting.
      Acceptance rates were not different between physician referrals and self
      referrals (25% vs. 18%; p=ns). The main reasons for ineligibility were no
      indication (39%); contraindications (metabolic, 21%; medical comorbidity, 17%;
      psychosocial, 8%) or personal factors (15%). CONCLUSIONS: Most referrals were
      received from people with diabetes, but acceptance rates were not significantly
      lower than for physician referrals. It will be important to increase awareness of
      severe hypoglycemia or glycemic lability as major indications for CIT among
      patients and physicians and to evaluate any impact this may have on the current
      acceptance rate of 19%.

PMID- 29212609
TI  - Effect of Combined Exercise Versus Aerobic-Only Training on Skeletal Muscle Lipid
      Metabolism in a Rodent Model of Type 1 Diabetes.
AB  - OBJECTIVES: Abnormal skeletal muscle lipid metabolism is associated with insulin
      resistance in people with type 1 diabetes. Although lipid metabolism is restored
      with aerobic exercise training, the risk for postexercise hypoglycemia is
      increased with this modality. Integrating resistance and aerobic exercise is
      associated with reduced hypoglycemic risk; however, the effects of this exercise
      modality on lipid metabolism and insulin resistance remain unknown. We compared
      the effects of combined (aerobic + resistance) versus aerobic exercise training
      on oxidative capacity and muscle lipid metabolism in a rat model of type 1
      diabetes. METHODS: Male Sprague-Dawley rats were divided into 4 groups: sedentary
      control (C), sedentary control + diabetes (CD), diabetes + high-intensity aerobic
      exercise (DAE) and diabetes + combined aerobic and resistance exercise (DARE).
      Following diabetes induction (20 mg/kg streptozotocin over five days), DAE rats
      ran for 12 weeks (5 days/week for 1 hour) on a motorized treadmill (27 m/min at a
      6-degree grade), and DARE rats alternated daily between running and incremental
      weighted ladder climbing. RESULTS: After training, DAE showed reduced muscle CD36
      protein content and lipid content compared to CD (p<=0.05). DAE rats also had
      significantly increased citrate synthase (CS) activity compared to CD (p<=0.05).
      DARE rats showed reduced CD36 protein content compared to CD and increased CS
      activity compared to CD and DAE rats (p<=0.05). DARE rats demonstrated increased
      skeletal muscle lipid staining, elevated lipin-1 protein content and insulin
      sensitivity (p<=0.05). CONCLUSIONS: Integration of aerobic and resistance
      exercise may exert a synergistic effect, producing adaptations characteristic of
      the "athlete's paradox," including increased capacity to store and oxidize
      lipids.

PMID- 29212610
TI  - Moving beyond symptom management towards cancer rehabilitation for older adults:
      Answering the 5W's.
AB  - Older adults with cancer are quickly becoming the largest group of cancer
      survivors. Chronological age is a poor predictor of cancer treatment outcomes and
      of the need for rehabilitation services. While newer symptom management systems
      and assessments are slowly becoming used in the clinic to improve communication
      between providers and survivors, such assessments are rarely used to trigger a
      referral to rehabilitation. Cancer rehabilitation for older adults with cancer
      has the potential to improve the quality of life and decrease disability caused
      by cancer and its treatments. One barrier to referral to cancer rehabilitation
      remains an understanding of what cancer rehabilitation is, and who, when, where,
      and why to refer to rehabilitation services. This report utilizes examples of
      three popular geriatric, distress and symptom measures to help answer these
      questions.

PMID- 29212611
TI  - Re: 'Public sentiment and discourse about Zika virus on Instagram'.

PMID- 29212612
TI  - Re: Letter to the Editor of Public Health in response to 'Public sentiment and
      discourse about Zika virus on Instagram'.

PMID- 29212613
TI  - Hyperglycemia and hyponatremia.

PMID- 29212615
TI  - Reply.

PMID- 29212614
TI  - Clinical trials in gynecologic oncology: Past, present, and future.
AB  - The Gynecologic Oncology Group has historically performed ground-breaking,
      practice-changing clinical trials in women's cancers. The current standard of
      care for initial treatment of ovarian, endometrial, cervical, and trophoblastic
      cancers was determined by clinical trials completed within this cooperative group
      structure. For example, trial GOG-0111 set the standard for combining platinum
      and taxane chemotherapy in ovarian cancer, and more recently GOG-0240 provided
      evidence for adding bevacizumab to chemotherapy for women with advanced cervical
      cancer. The landscape of clinical trial design has markedly changed in recent
      decades, with a clear emphasis on streamlining drug development towards specific
      patient populations and indications for investigational agents. Translational
      science in gynecologic cancers can set the stage for rapid and efficient
      introduction of new therapies for our patients. The gynecologic oncology
      community of researchers and clinicians is well positioned to enter into the new
      era of drug development, with breakthrough discoveries increasing each year. It
      is clear that we must incorporate smarter clinical trial design to get the right
      drugs to the right patients expeditiously, so we can continue to improve outcome
      for women with gynecologic cancers.

PMID- 29212616
TI  - Editorial Comment.

PMID- 29212617
TI  - Diagnostic Role of Anal Sphincter Relaxation Integral in High-Resolution
      Anorectal Manometry for Hirschsprung Disease in Infants.
AB  - OBJECTIVE: To investigate the possible diagnostic role of anal sphincter
      relaxation integral (ASRI) in high-resolution anorectal manometry (HRAM) for
      Hirschsprung disease. STUDY DESIGN: We performed conventional anorectal manometry
      (ARM) in 24 infants (8 with Hirschsprung disease and 16 without Hirschsprung
      disease) and HRAM in another 21 infants (9 with Hirschsprung disease and 12
      without Hirschsprung disease) before and after October 2014. All infants
      underwent rectal suction biopsy for confirmation of Hirschsprung disease. We
      quantified rectoanal inhibitory reflex (RAIR) adequacy by calculating the ASRI in
      HRAM study at pressure cutoffs of less than 10, 15, and 20 mm Hg (ASRI10, ASRI15,
      and ASRI20, respectively) and investigated the diagnostic utility. RESULTS:
      Patients with Hirschsprung disease who underwent HRAM had significantly lower
      ASRI10, ASRI15, and ASRI20 values than did infants without Hirschsprung disease
      (P = .0002, .0002, and .0003, respectively), indicating significant difference in
      internal anal sphincter relaxation during RAIR test between these 2 groups.
      ASRI10 exhibited a greater diagnostic accuracy, area under the curve,
      sensitivity, and specificity than did ASRI15 and ASRI20 for Hirschsprung disease.
      Moreover, the diagnostic accuracy of HRAM for Hirschsprung disease based on
      ASRI10 <7 mm Hg.s.cm was significantly greater than that of conventional ARM (P =
      .02). CONCLUSIONS: ASRI10 may be indicative of the adequacy of RAIR by HRAM in
      infants, thus assisting the diagnosis of Hirschsprung disease. The diagnostic
      accuracy of HRAM (based on the ASRI10 value) is greater than that of conventional
      ARM for Hirschsprung disease. ASRI10 may be used in an automatic HRAM analysis
      system for the diagnosis of anorectal motility disorders.

PMID- 29212619
TI  - Zinc Protoporphyrin-to-Heme Ratio and Ferritin as Measures of Iron Sufficiency in
      the Neonatal Intensive Care Unit.
AB  - OBJECTIVES: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios
      as biomarkers of iron status in neonates, determine how specific clinical events
      affected these measures, and assess how iron status changed during
      hospitalization. STUDY DESIGN: We performed a retrospective study of all infants
      with paired ferritin and ZnPP/H measurements between October 2014 and May 2016.
      Concordance of these measurements, effects of sepsis, red blood cell transfusion,
      erythropoietin treatment, and iron supplementation were assessed. Iron status was
      measured over time. RESULTS: A total of 228 patients (mean birth weight 1.3 kg,
      median gestational age 29 weeks) were evaluated. Mean log ZnPP/H values in
      infants with and without sepsis were not significantly different (4.98 umol/mol
      vs 4.97 umol/mol, adjusted P = .103), whereas log-transformed ferritin values
      increased significantly during infection (5.23 ng/mL vs 4.04 ng/mL, adjusted P <
      .001). Ferritin also increased more significantly than ZnPP/H following red blood
      cell transfusion (ferritin: mean 5.03 ng/mL vs 4.0 ng/mL, P < .001; ZnPP/H: mean
      4.85 umol/mol vs 4.98 umol/mol, P < .001). The mean iron supplementations at 30,
      60, and 90 days were 5.4, 6.9, and 7.4 mg/kg/day, respectively. Ferritin values
      decreased with advancing postnatal age (adjusted P < .001), with 66% of ferritin
      values less than 76 ng/mL. Treatment with erythropoietin increased ZnPP/H, but
      not ferritin levels. CONCLUSIONS: Ferritin is more significantly affected by
      inflammatory events such as sepsis and transfusion than ZnPP/H, thus, ZnPP/H may
      be a more reliable marker of iron status in this population. Infants showed
      worsening iron sufficiency over time despite supplementation above American
      Academy of Pediatrics guidelines.

PMID- 29212618
TI  - Altered Cerebral Perfusion in Infants Born Preterm Compared with Infants Born
      Full Term.
AB  - OBJECTIVES: To compare regional cerebral cortical blood flow (CBF) in infants
      born very preterm at term-equivalent age (TEA) and healthy newborns born full
      term and to examine the impact of clinical risk factors on CBF in the cohort born
      preterm. STUDY DESIGN: This prospective, cross-sectional study included infants
      born very preterm (gestational age at birth <32 weeks; birth weight <1500 g) and
      healthy infants born full term. Using noninvasive 3T arterial spin labeling
      magnetic resonance imaging, we quantified regional CBF in the cerebral cortex:
      sensorimotor/auditory/visual cortex, superior medial/dorsolateral prefrontal
      cortex, anterior cingulate cortex (ACC)/posterior cingulate cortex, insula, and
      lateral posterior parietal cortex, as well as in the brainstem, and deep gray
      matter. Analyses were performed controlling for sex, gestational age, and age at
      magnetic resonance imaging. RESULTS: We studied 202 infants: 98 born preterm and
      104 born full term at TEA. Infants born preterm demonstrated greater global CBF
      (beta = 9.03; P < .0001) and greater absolute regional CBF in all brain regions
      except the insula. Relative CBF in the insula, ACC and auditory cortex were
      decreased significantly in infants born preterm compared with their peers born at
      full term (P < .0001; P = .026; P = .036, respectively). In addition, the
      presence of parenchymal brain injury correlated with lower global and regional
      CBF (insula, ACC, sensorimotor, auditory, and visual cortices) whereas the need
      for cardiac vasopressor support correlated with lower regional CBF in the insula
      and visual cortex. CONCLUSIONS: Altered regional cortical CBF in infants born
      very preterm at TEA may reflect early brain dysmaturation despite the absence of
      cerebral cortical injury. Furthermore, specific cerebral cortical areas may be
      vulnerable to early hemodynamic instability and parenchymal brain injury.

PMID- 29212620
TI  - One-Year Outcome for Congenital Diaphragmatic Hernia: Results From the French
      National Register.
AB  - OBJECTIVE: To evaluate the status of congenital diaphragmatic hernia (CDH)
      management in France and to assess predictors of adverse outcomes. STUDY DESIGN:
      We reviewed the first-year outcome of all cases of CDH reported to the French
      National Register in 2011. RESULTS: A total of 158 cases were included. Of these,
      83% (131) were prenatally diagnosed, with a mortality rate of 39% (44 of 112) for
      live born infants with a known outcome at hospital discharge. Mortality increased
      to 47% (60 of 128) including those with termination of pregnancy and fetal loss.
      This contrasts with the 7% (2 of 27) mortality rate of the patients diagnosed
      postnatally (P = .002). Mortality worsened with 1 prenatal marker of CDH severity
      (OR 3.38 [1.30-8.83] P = .013) and worsened further with 2 markers (OR 20.64
      [5.29-80.62] P < .001). Classic postnatal risk factors of mortality such as side
      of hernia (nonleft P = .001), prematurity (P < .001), low birth weight (P =
      .002), and size of the defect (P < .001) were confirmed. Of the 141 live births
      (114 prenatal and 27 postnatal diagnosis) with known outcomes, 93 (67%) survived
      to hospital discharge, 68 (60%) with a prenatal diagnosis and 25 (93%) with a
      postnatal diagnosis. The median time to hospital discharge was 34 days (IQR,
      19.25-62). Of these survivors, 71 (76%) were followed up for 1 year. CONCLUSIONS:
      Despite advances in management of CDH, mortality was high and associated with
      prenatal risk factors. Postnatally, severe persistent pulmonary hypertension was
      difficult to predict and presented persistent challenges in management.

PMID- 29212621
TI  - Stenotic Lesions and the Maximum Diameter of Coronary Artery Aneurysms in
      Kawasaki Disease.
AB  - OBJECTIVES: To determine the prevalence of subsequent stenotic lesions based on
      the maximum diameter of the largest coronary artery aneurysm in patients with
      Kawasaki disease and the threshold value of coronary artery diameter associated
      with risk of developing stenotic lesion. STUDY DESIGN: There were 214 patients
      (160 males) who had at least 1 aneurysm in a selective coronary angiogram (CAG)
      done <100 days after the onset of Kawasaki disease were studied. We measured the
      maximal coronary artery aneurysm diameter in 3 major branches in the initial
      CAGs. Branches were classified into 3 groups according to their maximal coronary
      artery aneurysm diameter: large, >=8.0 mm; medium, >=6.0 mm but <8.0 mm; and
      small, <6.0 mm. Subsequent CAGs were performed in the late follow-up period. We
      investigated the stenotic lesion in the follow-up CAGs, and evaluated the
      prevalence of stenotic lesion in each group based on body surface area (BSA) by
      the Kaplan-Meier method. Localized stenosis of >=25% and complete occlusion were
      included as stenotic lesion in this study. We also determined the cutoff point
      for stenotic lesion. RESULTS: The median interval from the initial CAGs to the
      latest CAG was 8 years, with a maximum of 32 years. For a BSA of <0.50 m2, the 20
      year prevalence of large and medium stenotic lesions was 78% (n = 62; 95% CI, 63
      89) and 81% (n = 40; 95% CI, 63-89), respectively. For a BSA of >=0.50 m2, large
      and medium stenotic lesions were 82% (n = 75; 95% CI, 67-91) and 40% (n = 56; 95%
      CI, 20-64), respectively (P < .0001). CONCLUSION: The cutoff points of the
      coronary artery diameter within the first 100 days after the onset of Kawasaki
      disease leading to a stenotic lesion in the late period, were a diameter of >=6.1
      mm with a BSA of <0.50 m2 and a diameter of >=8.0 mm with a BSA of >=0.50 m2.
      Those cutoff points would have corresponded with a Z score of at least 10 on 2
      dimensional echocardiography. Careful follow-up and antithrombotic therapy should
      be provided to patients who meet these criteria.

PMID- 29212622
TI  - Improvement of Outcomes for Children with Down Syndrome.

PMID- 29212623
TI  - Intrauterine and Early Postnatal Exposure to Particulate Air Pollution and
      Kawasaki Disease: A Nationwide Longitudinal Survey in Japan.
AB  - OBJECTIVES: To examine the effects of prenatal and postnatal exposure to
      particulate matter on Kawasaki disease (KD) occurrence, using data from a
      nationwide population-based longitudinal survey in Japan that began in 2010.
      STUDY DESIGN: Prenatal and postnatal suspended particulate matter concentrations
      were obtained at municipality level and assigned to participants based on their
      municipality of birth. We analyzed data from 30 367 participants with data on
      either exposure period. We used hospital admission for KD from 6 to 30 months of
      age as the main outcome of interest. We conducted a multilevel logistic
      regression analysis, adjusting for individual and municipality-level variables.
      RESULTS: Children who were exposed to higher levels of suspended particulate
      matter, in particular during pregnancy, were more likely to be hospitalized for
      KD. The ORs for >=25 ug/m3 exposure compared with <20 ug/m3 exposure were 1.59
      (95% CI 1.06, 2.38) for prenatal exposure and 1.41 (0.82, 2.41) for postnatal
      exposure. Prenatal exposure during mid-to-late gestation seemed to be more
      relevant for the increased risk. CONCLUSIONS: Early life exposure to particulate
      air pollution, in particular during pregnancy, is associated with an increased
      risk of KD hospital admission in early childhood in a nationally representative
      sample in Japan.

PMID- 29212624
TI  - Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to
      Improve Quality and Safety.
AB  - OBJECTIVE: The Cancer Care Index (CCI), a single metric that sums the number of
      undesirable patient events in a given time frame (either preventable harm events
      or missed opportunities to provide optimal care), resulted in a 42% improvement
      in performance. Our objective was to test the index concept in other service
      lines to determine whether similar performance improvement occurred. STUDY
      DESIGN: Care indices were developed and introduced in 3 additional service lines:
      Nephrology (Chronic Kidney Disease Care Index; CKDCI), Pulmonology (Lung
      Transplantation Care Index; LTCI), and Otolaryngology (Tracheostomy Care Index;
      TCI). After reaching agreement on specific harms to be avoided and elements of
      optimal care that should be reliably delivered, these items were compiled into
      indices that were updated monthly. Reports included each element individually and
      the total for all elements. Baseline performance was calculated retrospectively
      for the previous year. RESULTS: Significant improvement in performance occurred
      in each program following implementation of the clinical indices. The CKDCI was
      decreased by 63.2% (P < .001), the LTCI was decreased by 89.5% (P < .001), and
      the TCI was decreased by 53.0% (P < .001). Surveyed staff indicated satisfaction
      with use of the metric. CONCLUSIONS: Clinical indices are useful for evaluating
      and managing the overall reliability of a program's ability to deliver optimal
      care, and are associated with improved clinical performance and satisfaction by
      service line staff when incorporated into a program's operation.

PMID- 29212625
TI  - Use of tricortical iliac crest strut autograft in comminuted posterior wall
      acetabular fractures: A case series.
AB  - PURPOSE: The results for fixation of comminuted posterior wall acetabular
      fractures are not very promising with reported complications in terms of
      osteoarthritis, nonunion and malunion which subsequently require conversion to
      total hip arthroplasty. The conversion to total hip arthroplasty is possible in
      patients over 50 years of age but not in younger patients. So this requires new
      methods for salvage of the native hip in young patients. METHODS: There were six
      patients in our series with highly comminuted posterior wall acetabular fractures
      where the fragments were excised and the gap filled with tricortical anterior
      iliac-crest strut autograft, fixed with screws and plate. RESULTS: Good results
      were achieved in four out of six patients analyzed clinically using the Merle
      d'Aubinge score modified by Matta and radiologically by Matta scoring. These
      patients have returned to original work and are walking independently. The good
      result in one patient deteriorated from good to poor between one and two years.
      One patient developed infection and excision arthroplasty was done. The graft
      incorporated well in five out of six patients. CONCLUSION: The use of iliac crest
      autograft is a better, advanced and promising technique as it provides a new wall
      to the weight bearing dome of the acetabulum for articulation with the femoral
      head. The rates of nonunion, malunion, post traumatic osteoarthritis are less as
      compared to the fixation of the comminuted fragments. The need for conversion to
      total hip arthroplasty is also less.

PMID- 29212626
TI  - A Lesser Known Side Effect of Tigecycline: Hypofibrinogenemia.

PMID- 29212627
TI  - How Do Infant Feeding Apps in China Measure Up? A Content Quality Assessment.
AB  - BACKGROUND: Globally, with the popularization of mobile phones, the number of
      health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the
      digital era, people are accessing health information through their fingertips. In
      China, there are several apps that claim to provide infant feeding and nutrition
      guidance. However, the quality of information in those apps has not been
      extensively assessed. OBJECTIVE: We aimed to assess the quality of Chinese infant
      feeding apps using comprehensive quality assessment criteria and to explore
      Chinese mothers' perceptions on apps' quality and usability. METHODS: We searched
      for free-to-download Chinese infant feeding apps in the iTunes and Android App
      Stores. We conducted a comprehensive assessment of the accountability, scientific
      basis, accuracy of information relevant to infant feeding, advertising policy,
      and functionality and carried out a preliminary screening of infant formula
      advertisements in the apps. In addition, we also conducted exploratory
      qualitative research through semistructured interviews with Chinese mothers in
      Shanghai to elicit their views about the quality of apps. RESULTS: A total of
      4925 apps were screened, and 26 apps that met the selection criteria were
      evaluated. All 26 apps were developed by commercial entities, and the majority of
      them were rated poorly. The highest total score was 62.2 (out of approximately
      100) and the lowest was 16.7. In the four quality domains assessed, none of them
      fulfilled all the accountability criteria. Three out of 26 apps provided
      information covering the three practices from the World Health Organization's
      infant feeding recommendations. Only one app described its advertising policy in
      its terms of usage. The most common app functionality was a built-in social forum
      (19/26). Provision of a website link was the least common functionality (2/26). A
      total of 20 out of 26 apps promoted infant formula banner advertisements on their
      homepages. In addition, 12 apps included both e-commerce stores and featured
      infant formula advertisements. In total, 21 mothers were interviewed face-to
      face. Mothers highly valued immediate access to parenting information and
      multifunctionality provided by apps. However, concerns regarding incredible
      information and commercial activities in apps, as well as the desire for
      information and support offered by health care professionals were expressed.
      CONCLUSIONS: The findings provide valuable information on Chinese infant feeding
      apps. The results are concerning, particularly with the relative absence of
      scientific basis and credibility and the large number of commercial
      advertisements that are displayed. Apps do seem to be able to provide an
      opportunity for mothers to access health information and support; it is time for
      tighter controls on content and advertisements. Ongoing app research and
      development should focus on implementation of a standard framework, which would
      drive the development of high-quality apps to support healthy infant feeding
      through cooperation among academics, health professionals, app users, app
      developers, and government bodies.

PMID- 29212628
TI  - Mobile Health Intervention to Increase Oral Cancer Therapy Adherence in Patients
      With Chronic Myeloid Leukemia (The REMIND System): Clinical Feasibility and
      Acceptability Assessment.
AB  - BACKGROUND: Optimal dosing of oral tyrosine kinase inhibitor therapy is critical
      to treatment success and survival of patients with chronic myeloid leukemia
      (CML). Drug intolerance secondary to toxicities and nonadherence are significant
      factors in treatment failure. OBJECTIVE: The objective of this study was to
      develop and pilot-test the clinical feasibility and acceptability of a mobile
      health system (REMIND) to increase oral drug adherence and patient symptom self
      management among people with CML (chronic phase). METHODS: A multifaceted
      intervention was iteratively developed using the intervention development
      framework by Schofield and Chambers, consisting of defining the patient problem
      and iteratively refining the intervention. The clinical feasibility and
      acceptability were examined via patient and intervention nurse interviews, which
      were audiotaped, transcribed, and deductively content analyzed. RESULTS: The
      intervention comprised 2 synergistically operating elements: (1) daily medication
      reminders and routine assessment of side effects with evidence-based self-care
      advice delivered in real time and (2) question prompt list (QPL) questions and
      routinely collected individual patient adherence and side effect profile data
      used to shape nurses' consultations, which employed motivational interviewing to
      support adoption of self-management behaviors. A total of 4 consultations and
      daily alerts and advice were delivered over 10 weeks. In total, 58% (10/17) of
      patients and 2 nurses participated in the pilot study. Patients reported several
      benefits of the intervention: help in establishing medication routines,
      resolution of symptom uncertainty, increased awareness of self-care, and informed
      decision making. Nurses also endorsed the intervention: it assisted in
      establishing pill-taking routines and patients developing effective solutions to
      adherence challenges. CONCLUSIONS: The REMIND system with nurse support was
      usable and acceptable to both patients and nurses. It has the potential to
      improve adherence and side-effect management and should be further evaluated.

PMID- 29212629
TI  - Patients' Acceptance of Smartphone Health Technology for Chronic Disease
      Management: A Theoretical Model and Empirical Test.
AB  - BACKGROUND: Chronic disease patients often face multiple challenges from
      difficult comorbidities. Smartphone health technology can be used to help them
      manage their conditions only if they accept and use the technology. OBJECTIVE:
      The aim of this study was to develop and test a theoretical model to predict and
      explain the factors influencing patients' acceptance of smartphone health
      technology for chronic disease management. METHODS: Multiple theories and factors
      that may influence patients' acceptance of smartphone health technology have been
      reviewed. A hybrid theoretical model was built based on the technology acceptance
      model, dual-factor model, health belief model, and the factors identified from
      interviews that might influence patients' acceptance of smartphone health
      technology for chronic disease management. Data were collected from patient
      questionnaire surveys and computer log records about 157 hypertensive patients'
      actual use of a smartphone health app. The partial least square method was used
      to test the theoretical model. RESULTS: The model accounted for .412 of the
      variance in patients' intention to adopt the smartphone health technology.
      Intention to use accounted for .111 of the variance in actual use and had a
      significant weak relationship with the latter. Perceived ease of use was affected
      by patients' smartphone usage experience, relationship with doctor, and self
      efficacy. Although without a significant effect on intention to use, perceived
      ease of use had a significant positive influence on perceived usefulness.
      Relationship with doctor and perceived health threat had significant positive
      effects on perceived usefulness, countering the negative influence of resistance
      to change. Perceived usefulness, perceived health threat, and resistance to
      change significantly predicted patients' intentions to use the technology. Age
      and gender had no significant influence on patients' acceptance of smartphone
      technology. The study also confirmed the positive relationship between intention
      to use and actual use of smartphone health apps for chronic disease management.
      CONCLUSIONS: This study developed a theoretical model to predict patients'
      acceptance of smartphone health technology for chronic disease management.
      Although resistance to change is a significant barrier to technology acceptance,
      careful management of doctor-patient relationship, and raising patients'
      awareness of the negative effect of chronic disease can negate the effect of
      resistance and encourage acceptance and use of smartphone health technology to
      support chronic disease management for patients in the community.

PMID- 29212631
TI  - Disruptive technologies making cancer care more patient centred.

PMID- 29212632
TI  - Community development is not so new.

PMID- 29212630
TI  - Clarifying the Concept of Adherence to eHealth Technology: Systematic Review on
      When Usage Becomes Adherence.
AB  - BACKGROUND: In electronic health (eHealth) evaluations, there is increasing
      attention for studying the actual usage of a technology in relation to the
      outcomes found, often by studying the adherence to the technology. On the basis
      of the definition of adherence, we suggest that the following three elements are
      necessary to determine adherence to eHealth technology: (1) the ability to
      measure the usage behavior of individuals; (2) an operationalization of intended
      use; and (3) an empirical, theoretical, or rational justification of the intended
      use. However, to date, little is known on how to operationalize the intended
      usage of and the adherence to different types of eHealth technology. OBJECTIVE:
      The study aimed to improve eHealth evaluations by gaining insight into when, how,
      and by whom the concept of adherence has been used in previous eHealth
      evaluations and finding a concise way to operationalize adherence to and intended
      use of different eHealth technologies. METHODS: A systematic review of eHealth
      evaluations was conducted to gain insight into how the use of the technology was
      measured, how adherence to different types of technologies was operationalized,
      and if and how the intended use of the technology was justified. Differences in
      variables between the use of the technology and the operationalization of
      adherence were calculated using a chi-square test of independence. RESULTS: In
      total, 62 studies were included in this review. In 34 studies, adherence was
      operationalized as "the more use, the better," whereas 28 studies described a
      threshold for intended use of the technology as well. Out of these 28, only 6
      reported a justification for the intended use. The proportion of evaluations of
      mental health technologies reporting a justified operationalization of intended
      use is lagging behind compared with evaluations of lifestyle and chronic care
      technologies. The results indicated that a justification of intended use does not
      require extra measurements to determine adherence to the technology. CONCLUSIONS:
      The results of this review showed that to date, justifications for intended use
      are often missing in evaluations of adherence. Evidently, it is not always
      possible to estimate the intended use of a technology. However, such measures do
      not meet the definition of adherence and should therefore be referred to as the
      actual usage of the technology. Therefore, it can be concluded that adherence to
      eHealth technology is an underdeveloped and often improperly used concept in the
      existing body of literature. When defining the intended use of a technology and
      selecting valid measures for adherence, the goal or the assumed working
      mechanisms should be leading. Adherence can then be standardized, which will
      improve the comparison of adherence rates to different technologies with the same
      goal and will provide insight into how adherence to different elements
      contributed to the outcomes.

PMID- 29212633
TI  - Preventing Alzheimer's dementia.

PMID- 29212634
TI  - Intravenous N-Acetylcysteine for Acetaminophen Toxicity.

PMID- 29212635
TI  - New Health Technologies Advancing Nursing Practice.

PMID- 29212636
TI  - Remote Clinical Nurse Specialist: Making a Difference From a Distance.

PMID- 29212637
TI  - Staffing Challenges Today.

PMID- 29212638
TI  - Reversal Strategies for Newer Oral Anticoagulants.
AB  - Nonvitamin K antagonist oral anticoagulants have advantages compared with
      warfarin, but both types of anticoagulants come with uncertainty about how best
      to manage life-threatening bleeding events, urgent surgeries, and invasive
      procedures. Nurse practitioners and physician assistants may need to manage such
      emergency situations in the critical care setting. Achieving hemostasis quickly
      is key, and efforts to do so have relied mainly on blood products. Targeted
      reversal agents are in clinical development and one, idarucizumab, which reverses
      dabigatran anticoagulation, has been approved. Current options for managing
      events and urgent procedures in anticoagulated patients are discussed in this
      article, with a focus on specific reversal agents.

PMID- 29212639
TI  - Advanced Practice Registered Nurses on Therapeutic Hypothermia Response Teams.
AB  - BACKGROUND: Therapeutic hypothermia can improve neurological recovery after
      cardiac arrest when implemented quickly. OBJECTIVE: To determine whether outcomes
      are improved among patients undergoing therapeutic hypothermia by adding advanced
      practice registered nurses to a therapeutic hypothermia response team. METHODS: A
      pilot quality improvement project was conducted in a Midwest community teaching
      hospital using a retrospective chart review of all adult patients undergoing
      therapeutic hypothermia before and after the addition of advanced practice
      registered nurses to the therapeutic hypothermia response team. Outcomes
      evaluated included time to target core body temperature, therapeutic hypothermia
      protocol initiation, discharge status, and hospital length of stay. RESULTS: A
      total of 14 adult patients (preintervention n = 8, postintervention n = 6)
      comprised the sample. Length of stay decreased in the postintervention group
      (median 2.5 vs 6 days for the preintervention group; P = .05), but other outcomes
      did not differ. CONCLUSIONS: This quality improvement project provides
      foundational data to evaluate advanced practice registered nurses specific
      metrics and to compare with future data using a larger longitudinal sample.

PMID- 29212640
TI  - Supporting Nurses in the Critical Care Environment.

PMID- 29212641
TI  - Incivility and Professional Comportment in Critical Care Nurses.
AB  - BACKGROUND: Civility among critical care nurses is important for achieving
      positive patient outcomes. Professional comportment refers to nurse behaviors
      that are respectful, knowledgeable, deliberate, and compassionate. OBJECTIVE: To
      examine the relationship between perceptions of nurse-to-nurse incivility and
      professional comportment among critical care nurses, and the extent to which
      nurse characteristics influence their perceptions. METHODS: Data were collected
      from nurses in 14 critical care units. Correlational analysis examined the
      relationship between nurses' perceptions of nurse-to-nurse incivility and
      professional comportment. Regression analysis was used to identify predictors of
      nurse-to-nurse incivility. RESULTS: Decreased perceptions of nurse-to-nurse
      incivility were associated with increased perceptions of professional
      comportment. Nurses' reports of receiving education about professional
      comportment was a significant predictor of increased nurse perceptions of
      professional comportment. CONCLUSION: Professional comportment education for
      critical care nurses is important and may provide an option to decrease
      incivility and promote healthy work environments for nurses.

PMID- 29212642
TI  - Compassion Fatigue and the Healthy Work Environment.
AB  - BACKGROUND: Burnout is a concern for critical care nurses in high-intensity
      environments. Studies have highlighted the importance of a healthy work
      environment in promoting optimal nurse and patient outcomes, but research
      examining the relationship between a healthy work environment and burnout is
      limited. OBJECTIVE: To examine how healthy work environment components relate to
      compassion fatigue (eg, burnout, secondary trauma) and compassion satisfaction.
      METHODS: Nurses (n = 105) in 3 intensive care units at an academic medical center
      completed a survey including the Professional Quality of Life and the American
      Association of Critical-Care Nurses' Healthy Work Environment standards. RESULTS:
      Regression models using each Healthy Work Environment component to predict each
      outcome, adjusting for background variables, showed that the 5 Healthy Work
      Environment components predicted burnout and that meaningful recognition and
      authentic leadership predicted compassion satisfaction. CONCLUSIONS: Findings on
      associations between healthy work environment standards and burnout suggest the
      potential importance of implementing the American Association of Critical-Care
      Nurses' Healthy Work Environment standards as a mechanism for decreasing burnout.

PMID- 29212643
TI  - Designing a Resilience Program for Critical Care Nurses.
AB  - BACKGROUND: Workplace stress can affect job satisfaction, increase staff turnover
      and hospital costs, and reduce quality of patient care. Highly resilient nurses
      adapt to stress and use a variety of skills to cope effectively. OBJECTIVE: To
      gain data on a mindfulness-based cognitive therapy resilience intervention for
      intensive care unit nurses to see if the intervention program would be feasible
      and acceptable. METHODS: Focus-group interviews were conducted by videoconference
      with critical care nurses who were members of the American Association of
      Critical-Care Nurses. The interview questions assessed the feasibility and
      acceptability of a mindfulness-based cognitive therapy program to reduce burnout
      syndrome in intensive care unit nurses. RESULTS: Thirty-three nurses participated
      in 11 focus groups. Respondents identified potential barriers to program
      adherence, incentives for adherence, preferred qualifications of instructors, and
      intensive care unit-specific issues to be addressed. CONCLUSIONS: The mindfulness
      based cognitive therapy pilot intervention was modified to incorporate thematic
      categories that the focus groups reported as relevant to intensive care unit
      nurses. Institutions that wish to design a resilience program for intensive care
      unit nurses to reduce burnout syndrome need an understanding of the barriers and
      concerns relevant to their local intensive care unit nurses.

PMID- 29212644
TI  - Creating Healthy Work Environments for Second Victims of Adverse Events.
AB  - Adverse events may cause a patient serious harm or death; the patient becomes the
      first victim of these events. The health care providers who become traumatized by
      the events are the second victims. These second victims experience feelings such
      as guilt, shame, sadness, and grief, which can lead to profound personal and
      professional consequences. An organizational culture of blame and a lack of
      support can intensify the provider's suffering. Second victims, as they move
      through predictable stages of recovery, can be positively influenced by a
      supportive organizational culture and the compassionate actions of peers,
      managers, advanced practice nurses, educators, and senior leaders. The American
      Association of Critical-Care Nurses Healthy Work Environment standards provide a
      framework for specific actions health care professionals should take to support
      colleagues during their recovery from adverse events.

PMID- 29212647
TI  - Evaluating Application of Research Findings to New Settings and Populations.

PMID- 29212648
TI  - Reflections on How We Teach Ethics: Moral Failure in Critical Care.

PMID- 29212649
TI  - Ventricular Aneurysm: Diagnosis and Treatment.

PMID- 29212650
TI  - Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and
      Postcardiac Transplantation.
AB  - BACKGROUND: NO bioavailability has not been systematically examined in congenital
      heart disease (CHD). To assess NO in patients with CHD, we measured nasal NO
      (nNO) generated by the nasal epithelia, given blood NO is difficult to measure
      (half-life, <2 ms). Given NO's role in hemodynamic regulation and the association
      of NO bioavailability with heart failure risk, we hypothesized NO levels may
      differ with varying severity of CHD physiologic characteristics. METHODS AND
      RESULTS: Six-hundred eighteen subjects, 483 with CHD and 135 controls, had nNO
      measured noninvasively via the nares using American Thoracic Society/European
      Respiratory Society guidelines. Subjects were dichotomized as having low or
      normal nNO based on age-specific cutoff values. Prevalence of low nNO was
      examined by various CHD physiologic feature types. Low nNO was more prevalent
      with CHD than controls (odds ratio, 2.28; P=0.001). A logistic regression model
      showed overall significance (P=0.035) for single ventricle, systemic right
      ventricle, ventricular dysfunction, oxygen desaturation, and heterotaxy
      predicting low nNO, with systemic right ventricle independently having twice the
      odds of low nNO (odds ratio, 2.04; P=0.014). Patients with low nNO had a higher
      risk of experiencing heart transplant or death (hazard ratio, 2.75; P=0.048), and
      heart transplant recipients (N=16) exhibited 5 times the odds of low nNO (69%
      versus 30%; odds ratio, 5.1; P=0.001). CONCLUSIONS: Patients with CHD have
      increased prevalence of low nNO, with highest odds seen with systemic right
      ventricle and heart transplant. Further studies are needed to investigate heart
      failure risks in patients with CHD with left versus right systemic ventricle
      physiologic characteristics and utility of low nNO for predicting heart failure
      risk.

PMID- 29212652
TI  - Personalised diet advice could tackle obesity, report advises.

PMID- 29212653
TI  - Policy makers ignore the role of evidence based treatment for opioid dependence.

PMID- 29212651
TI  - Relation Between Blood Pressure and Clinical Outcome in Hypertensive Subjects
      With Previous Stroke.
AB  - BACKGROUND: This study investigated whether a mean blood pressure (BP) of <130/80
      mm Hg is associated with further reduction in cardiovascular outcomes in treated
      hypertensive subjects with previous stroke. METHODS AND RESULTS: Subjects from
      the Korea National Health Insurance Service health examinee cohort diagnosed as
      having stroke and hypertension from January 1st, 2003 and December 31st, 2006
      (N=2320) were grouped according to mean systolic (<130, 130-<140, and >=140 mm
      Hg) and diastolic (<80, 80-<90, and >=90 mm Hg) BP recorded during follow-up
      health examinations. All-cause and cardiovascular mortality over 11 years were
      compared. Compared with subjects with a systolic BP of >=140 mm Hg (N=736),
      subjects with a systolic BP of 130 to <140 mm Hg (N=793) had a significantly
      lower risk of all-cause death (hazard ratio [HR], 0.61; 95% confidence interval
      [CI], 0.47-0.79; P<0.001), cardiovascular mortality (HR, 0.39; 95% CI, 0.25-0.61;
      P<0.001), and fatal ischemic stroke (HR, 0.25; 95% CI, 0.10-0.63; P=0.003).
      Systolic BP of <130 mm Hg (N=791) was associated with lower risk of nonfatal
      hemorrhagic stroke. Subjects with a diastolic BP of 80 to <90 mm Hg (N=1100) had
      significantly lower risk of all-cause death (HR, 0.60, 95% CI, 0.45-0.80;
      P<0.001) and cardiovascular mortality (HR, 0.45; 95% CI, 0.30-0.70; P<0.001) than
      those with a diastolic BP of >=90 mm Hg (N=342). Diastolic BP of <80 mm Hg
      (N=878) was associated with reduced risk of nonfatal hemorrhagic stroke and
      further lowering of all-cause mortality and cardiovascular mortality.
      CONCLUSIONS: BP of <130/80 mm Hg was associated with improved outcomes in
      hypertensive subjects with previous stroke.

PMID- 29212655
TI  - Brexit is shifting drug industry's focus away from UK, MPs hear.

PMID- 29212654
TI  - I thought I wasn't thin enough to be anorexic.

PMID- 29212656
TI  - The relevance and implications of signet-ring cell adenocarcinoma of the
      oesophagus.
AB  - AIM: To review the current understanding of signet-ring type oesophageal
      adenocarcinoma including evidence for prognosis. METHODS: We conducted a
      literature search of nine healthcare literature databases for articles detailing
      the biology and clinical outcomes of signet-ring cell adenocarcinoma of the
      oesophagus. The impact of signet-ring cell morphology was analysed and detailed
      in written text and tabular format. Current understanding of the biology of
      signet-ring cell adenocarcinoma of the oesophagus was summarised. RESULTS: Signet
      ring cell carcinoma was represented in 7.61% of the 18 989 cases of oesophageal
      carcinoma reviewed in multiple studies. The presence of signet-ring cells
      conferred a worse prognosis and these tumours responded differently to
      conventional treatments as compared with typical adenocarcinoma. Little is known
      about the biological features of signet-ring cell adenocarcinoma of the
      oesophagus. Work in gastric lesions has identified potential targets for future
      treatments such as CDH1 and RHOA genes. Categorisation of signet-ring cell
      carcinomas by the proportion of signet-ring cells within tumours differs among
      clinicians despite WHO criteria for classification. The current UK guidelines for
      histopathological reporting of oesophageal tumours do not emphasise the
      importance of identifying signet-ring cells. CONCLUSION: The presence of signet
      ring cells in oesophageal adenocarcinomas leads to poorer clinical outcomes.
      Current understanding of signet-ring cell biology in oesophageal cancer is
      limited.

PMID- 29212657
TI  - Venous invasion detection in colorectal cancer specimens: risk assessment of
      modifying the dissection method using a tangential approach.

PMID- 29212658
TI  - A new mitofusin topology places the redox-regulated C terminus in the
      mitochondrial intermembrane space.
AB  - Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and
      fungi. It is essential for cellular homeostasis, and yet the underlying
      mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions
      revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from
      one another and lack strong sequence similarity. Bioinformatic analysis showed
      that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas
      metazoan Mitofusins contain only a single transmembrane domain. This prediction
      contradicts the current models, suggesting that both animal and fungal proteins
      share one topology. This newly predicted topology of Mfn1 and Mfn2 was
      demonstrated biochemically, confirming that the C-terminal, redox-sensitive
      cysteine residues reside within the intermembrane space (IMS). Functional
      experiments established that redox-mediated disulfide modifications within the
      IMS domain are key modulators of reversible Mfn oligomerization that drives
      fusion. Together, these results lead to a revised understanding of Mfns as single
      spanning outer membrane proteins with an Nout-Cin orientation, providing
      functional insight into the IMS contribution to redox-regulated fusion events.

PMID- 29212660
TI  - Joanna Poulton: Research is in my DNA.

PMID- 29212659
TI  - Unconventional secretion of FABP4 by endosomes and secretory lysosomes.
AB  - An appreciation of the functional properties of the cytoplasmic fatty acid
      binding protein 4 (FABP4) has advanced with the recent demonstration that an
      extracellular form secreted by adipocytes regulates a wide range of physiological
      functions. Little, however, is known about the mechanisms that mediate the
      unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is
      mediated by a membrane-bounded compartment, independent of the conventional
      endoplasmic reticulum-Golgi secretory pathway. We show that FABP4 secretion is
      also independent of GRASP proteins, autophagy, and multivesicular bodies but
      involves enclosure within endosomes and secretory lysosomes. We highlight the
      physiological significance of this pathway with the demonstration that an
      increase in plasma levels of FABP4 is inhibited by chloroquine treatment of mice.
      These findings chart the pathway of FABP4 secretion and provide a potential
      therapeutic means to control metabolic disorders associated with its dysregulated
      secretion.

PMID- 29212661
TI  - Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic
      repression.
AB  - Epigenetic maintenance of gene repression is essential for development. Polycomb
      complexes are central to this memory, but many aspects of the underlying
      mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb
      deposited H3K27me3 and is required for repression of many Polycomb target genes
      in Arabidopsis Here we show that LHP1 binds RNA in vitro through the
      intrinsically disordered hinge region. By independently perturbing the RNA
      binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27)
      recognition, we found that both facilitate LHP1 localization and H3K27me3
      maintenance. Disruption of the RNA-binding hinge region also prevented formation
      of subnuclear foci, structures potentially important for epigenetic repression.

PMID- 29212663
TI  - Margaret McCartney: Scottish GP contract-responsibility without power?

PMID- 29212662
TI  - Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear
      export.
AB  - Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of
      synthesis, to the cytoplasm, their site of function for protein synthesis. The
      evolutionarily conserved beta-importin family member Los1 (Exportin-t) has been
      the only exporter known to execute nuclear export of newly transcribed intron
      containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms.
      As tRNA nuclear export is essential, we previously interrogated the budding yeast
      proteome to identify candidates that function in tRNA nuclear export. Here, we
      provide molecular, genetic, cytological, and biochemical evidence that the Mex67
      Mtr2 (TAP-p15) heterodimer, best characterized for its essential role in mRNA
      nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of
      Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the
      nucleus. Remarkably, merely fivefold overexpression of Mex67-Mtr2 can substitute
      for Los1 in los1Delta cells. Moreover, in vivo coimmunoprecipitation assays with
      tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA
      exporters surprisingly exhibit differential tRNA substrate preferences. The
      existence of multiple tRNA exporters, each with different tRNA preferences, may
      indicate that the proteome can be regulated by tRNA nuclear export. Thus, our
      data show that Mex67-Mtr2 functions in primary nuclear export for a subset of
      yeast tRNAs.

PMID- 29212665
TI  - Association between individual and neighbourhood socioeconomic factors and
      masticatory efficiency: a cross-sectional analysis of the Paris Prospective Study
      3.
AB  - BACKGROUND: There is a lack of evidence on the impact of socioeconomic factors on
      masticatory efficiency. The present study investigates the relationship between
      individual and neighbourhood socioeconomic factors (main exposure) and the number
      of masticatory units (MUs) used as surrogate of the masticatory efficiency (main
      outcome). METHODS: In this cross-sectional study nested in the Paris Prospective
      Study 3, 4270 adults aged 50-75 and recruited from 13 June 2008 to 31 May 2012
      underwent a full-mouth examination. Number of MUs defined as pairs of opposing
      teeth or dental prostheses allowing mastication, number of missing teeth and
      gingival inflammation were documented. The individual component of the
      socioeconomic status was evaluated with an individual multidimensional
      deprivation score and education level. The neighbourhood component of the
      socioeconomic status was evaluated with the FDep99 deprivation index.
      Associations were quantified using marginal models. RESULTS: In multivariate
      analyses, having less than 5 MUs was associated with (1) the most deprived
      neighbourhoods (OR=2.27 (95% CI 1.63 to 3.17)), (2) less than 12 years of
      educational attainment (OR=2.20 (95% CI 1.66 to 2.92)) and (3) the highest
      individual score of deprivation (OR=3.23 (95% CI 2.24 to 4.65)). Associations
      with education and individual score of deprivation were consistent across the
      level of neighbourhood deprivation. Comparable associations were observed with
      the number of missing teeth. Associations with gingival inflammation were of
      lower magnitude; the relationship was present for deprivation markers but not for
      education. CONCLUSION: Poor masticatory efficiency is associated with low
      educational attainment and high deprivation scores.

PMID- 29212664
TI  - Genetic bypass of essential RNA repair enzymes in budding yeast.
AB  - RNA repair enzymes catalyze rejoining of an RNA molecule after cleavage of
      phosphodiester linkages. RNA repair in budding yeast is catalyzed by two separate
      enzymes that process tRNA exons during their splicing and HAC1 mRNA exons during
      activation of the unfolded protein response (UPR). The RNA ligase Trl1 joins
      2',3'-cyclic phosphate and 5'-hydroxyl RNA fragments, creating a phosphodiester
      linkage with a 2'-phosphate at the junction. The 2'-phosphate is removed by the
      2'-phosphotransferase Tpt1. We bypassed the essential functions of TRL1 and TPT1
      in budding yeast by expressing "prespliced," intronless versions of the 10
      normally intron-containing tRNAs, indicating this repair pathway does not have
      additional essential functions. Consistent with previous studies, expression of
      intronless tRNAs failed to rescue the growth of cells with deletions in
      components of the SEN complex, implying an additional essential role for the
      splicing endonuclease. The trl1Delta and tpt1Delta mutants accumulate tRNA and
      HAC1 splicing intermediates indicative of RNA repair defects and are
      hypersensitive to drugs that inhibit translation. Failure to induce the unfolded
      protein response in trl1Delta cells grown with tunicamycin is lethal owing to
      their inability to ligate HAC1 after its cleavage by Ire1. In contrast, tpt1Delta
      mutants grow in the presence of tunicamycin despite reduced accumulation of
      spliced HAC1 mRNA. We optimized a PCR-based method to detect RNA 2'-phosphate
      modifications and show they are present on ligated HAC1 mRNA. These RNA repair
      mutants enable new studies of the role of RNA repair in cellular physiology.

PMID- 29212667
TI  - Lung tissue gene-expression signature for the ageing lung in COPD.
AB  - INTRODUCTION: COPD is a chronic, progressive, inflammatory disease of the lungs
      and the third leading cause of death worldwide. The current knowledge of the
      pathophysiology of COPD is limited and novel insights in underlying disease
      mechanisms are urgently needed. Since there are clear parallels between ageing
      and COPD, we investigated genes underlying lung ageing in general and abnormal
      lung ageing in COPD. METHODS: Whole genome mRNA profiling was performed on lung
      tissue samples (n=1197) and differential gene expression with increasing age was
      analysed using an adjusted linear regression model. Subsequent pathway analysis
      was performed using GeneNetwork and the gene-expression signature was compared
      with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of
      patients with COPD (n=311) and non-COPD controls (n=270), we performed an
      interaction analysis between age and COPD to identify genes differentially
      expressed with age in COPD compared with controls, followed by gene set
      enrichment pathway analysis. RESULTS: We identified a strong gene-expression
      signature for lung ageing with 3509 differentially expressed genes, of which
      33.5% were found nominal significant in the GTEx project. Interestingly, we found
      EDA2R as a strong candidate gene for lung ageing. The age*COPD interaction
      analysis revealed 69 genes significantly differentially expressed with age
      between COPD and controls. CONCLUSIONS: Our study indicates that processes
      related to lung development, cell-cell contacts, calcium signalling and immune
      responses are involved in lung ageing in general. Pathways related to
      extracellular matrix, mammalian target of rapamycin signalling, splicing of
      introns and exons and the ribosome complex are proposed to be involved in
      abnormal lung ageing in COPD.

PMID- 29212668
TI  - Unexpected migration.

PMID- 29212666
TI  - STAT4 and T-bet control follicular helper T cell development in viral infections.
AB  - Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and
      proliferation and guide their differentiation and immunoglobulin isotype
      switching by delivering contact-dependent and soluble factors, including IL-21,
      IL-4, IL-9, and IFN-gamma. IL-21 and IFN-gamma are coexpressed by Tfh cells
      during viral infections, but transcriptional regulation of these cytokines is not
      completely understood. In this study, we show that the T helper type 1 cell (Th1
      cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh
      cells after acute viral infection, with a temporal decline in T-bet in the waning
      response. T-bet is important for Tfh cell production of IFN-gamma, but not IL-21,
      and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection,
      is required for expression of T-bet and Bcl6 and for IFN-gamma and IL-21. These
      data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required
      alongside STAT4 to coordinate Tfh cell IL-21 and IFN-gamma production and for
      promotion of the GC response after acute viral challenge.

PMID- 29212670
TI  - Repeated measurement of Mo2 in small aquatic organisms: a manual intermittent
      flow respirometer using off-the-shelf components.
AB  - Measurement of rates of oxygen consumption ( Mo2) in small aquatic embryos or
      larvae (<1 mm) in response to altered environmental conditions has traditionally
      been challenging. Here, using modifications of a commercially available
      fluorescent optode flow-through cell (FTC; PreSens FTC-PSt3) and routine
      laboratory supplies (syringes, stopcocks, tubing), we have constructed a manual
      intermittent flow respirometer (MIFR) that allows measurement of Mo2 in small
      numbers of individuals when sequentially exposed to different environmental
      conditions (e.g., changes in seawater pH) through a gravity-driven media
      replacement perfusion system. We first show that the FTC can be used in "static"
      mode while incubating small numbers of embryos/larvae contained within the planar
      oxygen sensor (POS) chamber with Nitex filters. We then demonstrate the use of
      the MIFR by exposing larval echinoderms ( Fellaster zelandiae, Evechinus
      chloroticus, and Centrostephanus rodgersii) to seawater equilibrated with
      elevated CO2 and measured Mo2 during acute and chronic exposure to hypercapnia.
      This MIFR method will allow investigators to address questions regarding the
      respiratory physiology of small aquatic animals, such as the thresholds for
      metabolic depression in embryonic and larval forms. NEW & NOTEWORTHY A manual
      intermittent flow respirometer (MIFR), allowing media exchange in a flow-through
      cell containing small aquatic organisms, permits repeated measurement of Mo2 of
      individuals not only in a single medium (e.g., technical replication), but also
      in different media (here, high CO2-equilibrated seawater), enabling measurement
      of acute physiological responses to changed conditions. This versatile technique
      has wide-ranging implications for the study of the Mo2 response of aquatic
      organisms in the face of climate change.

PMID- 29212669
TI  - Long-duration bed rest modifies sympathetic neural recruitment strategies in male
      and female participants.
AB  - To understand the impact of physical deconditioning with head-down tilt bed rest
      (HDBR) on the malleability of sympathetic discharge patterns, we studied 1)
      baseline integrated muscle sympathetic nerve activity (MSNA; microneurography)
      from 13 female participants in the WISE-2005 60-day HDBR study (retrospective
      analysis), 2) integrated MSNA and multiunit action potential (AP) analysis in 13
      male participants performed on data collected at baseline and during
      physiological stress imposed by end-inspiratory apnea in a new 60-day HDBR study,
      and 3) a repeatability study (control; n = 6, retrospective analysis, 4 wk
      between tests). Neither baseline integrated burst frequency nor incidence were
      altered with HDBR (both P > 0.35). However, baseline integrated burst latency
      increased in both HDBR studies (male: 1.35 +/- 0.02 to 1.39 +/- 0.02 s, P < 0.01;
      female: 1.23 +/- 0.02 to 1.29 +/- 0.02 s, P < 0.01), whereas controls exhibited
      no change across two visits (1.25 +/- 0.02 to 1.25 +/- 0.02 s, group-by-time
      interaction, P = 0.02). With the exception of increased AP latency ( P = 0.03),
      male baseline AP data did not change with HDBR (all P > 0.19). The change in AP
      frequency on going from baseline to apnea (?94 +/- 25 to ?317 +/- 55 AP/min, P <
      0.01) and the number of active sympathetic clusters per burst (?0 +/- 0.2 to ?1
      +/- 0.2 clusters/burst, P = 0.02) were greater post- compared with pre-HDBR. The
      change in total clusters with apnea was ?0 +/- 0.5 clusters pre- and ?2 +/- 0.7
      clusters post-HDBR ( P = 0.07). These data indicate that 60-day HDBR modified
      discharge characteristics in baseline burst latency and sympathetic neural
      recruitment during apneic stress. NEW & NOTEWORTHY Long-duration bed rest did not
      modify baseline sympathetic burst frequency in male and female participants, but
      examination of additional features of the multiunit signal provided novel
      evidence to suggest augmented synaptic delays or processing times at baseline for
      all sympathetic action potentials. Furthermore, long-duration bed rest increased
      reflex-sympathetic arousal to apneic stress in male participants primarily by
      mechanisms involving an augmented firing rate of action potential clusters active
      at baseline.

PMID- 29212671
TI  - Influence of age and gender on the phase and strength of the relation between
      heart period and systolic blood pressure spontaneous fluctuations.
AB  - Aging affects baroreflex regulation. The effect of senescence on baroreflex
      control was assessed from spontaneous fluctuations of heart period (HP) and
      systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase
      and strength are usually disregarded. This study checks whether the HP-SAP phase
      and strength, as estimated, respectively, via the phase of the HP-SAP cross
      spectrum (PhHP-SAP) and squared coherence function (K2HP-SAP), vary with age in
      healthy individuals and trends are gender-dependent. We evaluated 110 healthy
      volunteers (55 males) divided into five age subgroups (21-30, 31-40, 41-50, 51
      60, and 61-70 yr). Each subgroup was formed by 22 subjects (11 males). HP series
      was extracted from electrocardiogram and SAP from finger arterial pressure at
      supine resting (REST) and during active standing (STAND). PhHP-SAP and K2HP-SAP
      functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high
      frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND PhHP-SAP(LF)
      showed a negative correlation with age regardless of gender even though values
      were more negative in women. This trend was shown to be compatible with a
      progressive increase of the baroreflex latency with age. At REST K2HP-SAP(LF)
      decreased with age regardless of gender, but during STAND the high values of K2HP
      SAP(LF) were more preserved in men than women. At REST and during STAND the
      association of PhHP-SAP(HF) and K2HP-SAP(HF) with age was absent. The findings
      points to a greater instability of baroreflex control with age that seems to
      affect to a greater extent women than men. NEW & NOTEWORTHY Aging increases
      cardiac baroreflex latency and decreases the degree of cardiac baroreflex
      involvement in regulating cardiovascular variables. These trends are gender
      independent but lead to longer delays and asmaller degree of cardiac baroreflex
      involvement in women than in men, especially during active standing, with
      important implications on the tolerance to an orthostatic stressor.

PMID- 29212672
TI  - Cardiovascular response to prescribed detraining among recreational athletes.
AB  - Exercise-induced cardiac remodeling (EICR) and the attendant myocardial
      adaptations characteristic of the athlete's heart may regress during periods of
      exercise reduction or abstinence. The time course and mechanisms underlying this
      reverse remodeling, specifically the impact of concomitant plasma volume (PV)
      contraction on cardiac chamber size, remain incompletely understood. We therefore
      studied recreational runners ( n = 21, age 34 +/- 7 yr; 48% male) who completed
      an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after
      which total exercise exposure was confined to <2 h/wk (no single session >1 h)
      for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed
      at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed
      linear modeling adjusting for age, sex, Vo2peak, and marathon finish time was
      used to compare data across time points. Physiological detraining was evidenced
      by serial reductions in treadmill performance. Two distinct phases of myocardial
      remodeling and hematological adaptation were observed. After 4 wk of detraining,
      there were significant reductions in PV (Delta -6.0%, P < 0.01), left ventricular
      (LV) wall thickness (Delta -8.1%, <0.05), LV mass (Delta -10.3%, P < 0.001), and
      right atrial area (Delta -8.2%, P < 0.001). After 8 wk of detraining, there was a
      significant reduction in right ventricle chamber size (end-diastolic area Delta =
      -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall
      thickness. Abrupt reductions in exercise training stimulus result in a structure
      specific time course of reverse cardiac remodeling that occurs largely
      independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac
      remodeling, previously documented among competitive athletes, extends to
      recreational runners and occurs with a distinct time course. Initial reductions
      in plasma volume and left ventricular (LV) mass, driven by reductions in wall
      thickness, are followed by contraction of the right ventricle. Consistent with
      data from competitive athletes, LV chamber volumes appear less responsive to
      detraining and may be a more permanent adaptation to sport.

PMID- 29212673
TI  - 70 not out, and the best is yet to come: celebrating 70 years of orthopaedic
      excellence.

PMID- 29212674
TI  - Iatrogenic articular cartilage injury: the elephant in the operating theatre: the
      surgeons' role in chondroprotection.

PMID- 29212675
TI  - What surgeons need to know about infographics.

PMID- 29212676
TI  - What surgeons need to know about infographics.

PMID- 29212677
TI  - The minimum follow-up required for radial head arthroplasty: a meta-analysis.
AB  - AIMS: The primary aim of this study was to define the standard minimum follow-up
      required to produce a reliable estimate of the rate of re-operation after radial
      head arthroplasty (RHA). The secondary objective was to define the leading
      reasons for re-operation. MATERIALS AND METHODS: Four electronic databases,
      between January 2000 and March 2017 were searched. Articles reporting reasons for
      re-operation (Group I) and results (Group II) after RHA were included. In Group
      I, a meta-analysis was performed to obtain the standard minimum follow-up, the
      mean time to re-operation and the reason for failure. In Group II, the minimum
      follow-up for each study was compared with the standard minimum follow-up.
      RESULTS: A total of 40 studies were analysed: three were Group I and included 80
      implants and 37 were Group II and included 1192 implants. In Group I, the mean
      time to re-operation was 1.37 years (0 to 11.25), the standard minimum follow-up
      was 3.25 years; painful loosening was the main indication for re-operation. In
      Group II, 33 Group II articles (89.2%) reported a minimum follow-up of < 3.25
      years. CONCLUSION: The literature does not provide a reliable estimate of the
      rate of re-operation after RHA. The reproducibility of results would be improved
      by using a minimum follow-up of three years combined with a consensus of the
      definition of the reasons for failure after RHA. Cite this article: Bone Joint J
      2017;99-B:1561-70.

PMID- 29212678
TI  - The myths of 'big data' in health care.
AB  - 'Big data' is a term for data sets that are so large or complex that traditional
      data processing applications are inadequate. Billions of dollars have been spent
      on attempts to build predictive tools from large sets of poorly controlled
      healthcare metadata. Companies often sell reports at a physician or facility
      level based on various flawed data sources, and comparative websites of 'publicly
      reported data' purport to educate the public. Physicians should be aware of
      concerns and pitfalls seen in such data definitions, data clarity, data
      relevance, data sources and data cleaning when evaluating analytic reports from
      metadata in health care. Cite this article: Bone Joint J 2017;99-B:1571-6.

PMID- 29212679
TI  - Complications following arthroscopic surgery of the hip: a systematic review of
      36 761 cases.
AB  - AIMS: The number of patients undergoing arthroscopic surgery of the hip has
      increased significantly during the past decade. It has now become an established
      technique for the treatment of many intra- and extra-articular conditions
      affecting the hip. However, it has a steep learning curve and is not without the
      risk of complications. The purpose of this systematic review was to determine the
      prevalence of complications during and following this procedure. MATERIALS AND
      METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines were used in designing this study. Two reviewers systematically
      searched the literature for complications related to arthroscopy of the hip. The
      research question and eligibility criteria were established a priori. Pertinent
      data were abstracted and analysed. RESULTS: We found 276 relevant studies with a
      total of 36 761 arthroscopies that met the inclusion criteria. The mean age of
      the patients was 36.7 years (1.7 to 70) and the mean body mass index was 25.7
      kg/m2 (20.2 to 29.2). Femoroacetabular impingement and labral tears were the most
      common indications for the procedure. The total number of complications was 1222
      (3.3%). Nerve injury (0.9%), mainly involving the pudendal and lateral femoral
      cutaneous nerves, and iatrogenic chondral and labral injury (0.7%), were the two
      most common complications. There were 58 major complications (0.2%), the most
      common being intra-abdominal extravasation of fluid, which was found in 13 cases
      (0.04%). There were three deaths (0.008%). CONCLUSION: Arthroscopic surgery of
      the hip is a procedure with a relatively low rate of complications, although some
      may be significant in this young cohort of patients. This study relied on the
      reported complications only and the results should be interpreted with caution.
      Cite this article: Bone Joint J 2017;99-B:1577-83.

PMID- 29212680
TI  - High prevalence of acetabular retroversion in asymptomatic adults: a 3D CT-based
      study.
AB  - AIMS: This study sought to establish the prevalence of the cross over sign (COS)
      and posterior wall sign (PWS) in relation to the anterior pelvic plane (APP) in
      an asymptomatic population through reliable and accurate 3D-CT based assessment.
      MATERIALS AND METHODS: Data from pelvic CT scans of 100 asymptomatic subjects
      (200 hips) undertaken for conditions unrelated to disorders of the hip were
      available for analysis in this study. A previously established 3D analysis method
      was applied to assess the prevalence of the COS and PWS in relation to the APP.
      RESULTS: Of the 200 included hips, 24% (48) presented a positive COS and 5.5%
      (11) presented a positive PWS. A combination of COS and PWS was observed in 1%
      (two) of all hips (1%). CONCLUSION: The high incidence of acetabular
      retroversion, determined by the COS, shows that this anatomic configuration may
      not differ in frequency between asymptomatic individuals and patients with
      symptomatic femoroacetabular impingement (FAI). Patients presenting with hip pain
      and evidence of FAI should be subjected to strict diagnostic scrutiny and
      evaluated in the sum of their clinical and radiological presentation. In our
      cohort of asymptomatic adults, the COS showed a higher incidence than the PWS or
      a combined COS/PWS. Cite this article: Bone Joint J 2017;99-B:1584-9.

PMID- 29212681
TI  - Ten-year follow-up study of three alternative bearing surfaces used in total hip
      arthroplasty in young patients: a prospective randomised controlled trial.
AB  - AIMS: We present the ten-year data of a cohort of patients, aged between 18 and
      65 years (mean age 52.7 years; 19 to 64), who underwent total hip arthroplasty.
      Patients were randomised to be treated with a cobalt-chrome (CoCr) femoral head
      with an ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked
      polyethylene (XLPE) or ceramic-on-ceramic (CoC) bearing surface. PATIENTS AND
      METHODS: A total of 102 hips (91 patients) were randomised into the three groups.
      At ten years, 97 hips were available for radiological and functional follow-up.
      Two hips (two patients) had been revised (one with deep infection and one for
      periprosthetic fracture) and three were lost to follow-up. Radiological analysis
      was performed using a validated digital assessment programme to give linear,
      directional and volumetric wear of the two polyethylene groups. RESULTS: There
      was a significantly reduced rate of steady-state linear wear with XLPE (0.07
      mm/yr) compared with UHMWPE (0.37 mm/yr) (p = 0.001). Volumetric wear was also
      significantly reduced in the XLPE group (29.29 mm3/yr) compared with the UHMWPE
      group (100.75mm3/yr) (p = 0.0001). There were six patients with UHMWPE who had
      non-progressive osteolysis and none in the XLPE group. All three bearing groups
      had significant improvements in 12-item short form health survey scores, Western
      Ontario and McMaster Universities Osteoarthritis Index score and Harris Hip
      Score. However, the improvement in HSS was significantly less in the UHMWPE group
      (p = 0.0188) than in the other two groups. At ten years, the rates of volumetric
      and linear wear in the XLPE group remain low and predominantly below the
      estimated threshold for osteolysis (1 mm/yr). The rate of linear wear in the XLPE
      group was three times less than in the UHMWPE group at five-year follow-up and
      five times less at ten years. The rate of volumetric wear was also three times
      less in the XLPE group at ten years. CONCLUSION: While CoC also performs well,
      XLPE at ten years remains a safe and excellent bearing option in young patients,
      with low rates of wear and no evidence of osteolysis. Cite this article: Bone
      Joint J 2017;99-B:1590-5.

PMID- 29212682
TI  - Stable migration of peri-apatite-coated uncemented tibial components in a
      multicentre study.
AB  - AIMS: Hydroxyapatite coatings for uncemented fixation in total knee arthroplasty
      can theoretically provide a long-lasting biological interface with the host bone.
      The objective of this study was to test this hypothesis with propriety
      hydroxyapatite, peri-apatite, coated tibial components using component migration
      measured with radiostereometric analysis over two years as an indicator of long
      term fixation. PATIENTS AND METHODS: A total of 29 patients at two centres
      received uncemented PA-coated tibial components and were followed for two years
      with radiostereometric analysis exams to quantify the migration of the component.
      RESULTS: While there was significant variation in individual migration patterns,
      the overall migration of the tibial component in the study group demonstrated a
      pattern of initial migration followed by stabilisation after one year, with mean
      maximum total point motion (MTPM) of 0.02 mm (standard deviation (sd) 0.20)
      between one and two years post-operatively. The direction of greatest motion was
      subsidence, which stabilised at three months post-operatively (mean translation
      of 0.21 mm, sd 0.40). CONCLUSION: The tibial component migration pattern of
      stabilisation in the second post-operative year is indicative of successful long
      term fixation for this PA-coated tibial component. Cite this article: Bone Joint
      J 2017;99-B:1596-1602.

PMID- 29212683
TI  - 'Hot Joints' infection protocol reduces unnecessary post-operative re-admissions
      following total hip and knee arthroplasty.
AB  - AIMS: To evaluate the effectiveness of an institutionally developed algorithm for
      evaluation and diagnosis of prosthetic joint injection and to determine the
      impact of this protocol on overall hospital re-admissions.p PATIENTS AND METHODS:
      We retrospectively evaluated 2685 total hip arthroplasty (THA) and total knee
      arthroplasty (TKA) patients prior to (1263) and following (1422) the introduction
      of an infection detection protocol. The protocol used conservative thresholds for
      C-reactive protein to direct the medical attendant to aspirate the joint. The
      protocol incorporated a clear set of laboratory and clinical criteria that
      allowed a patient to be discharged home if all were met. Patients were included
      if they presented to our emergency department within 120 days post-operatively
      with concerns for swelling, pain or infection and were excluded if they had an
      unambiguous infection or if their chief complaint was non-orthopaedic in nature.
      RESULTS: Concern for infection was the single most common (32%) reason for
      presentation. A total of 296 patients made an emergency visit and were included
      following THA or TKA. In the pre-protocol cohort, 11 of 27 patients were formally
      re-admitted to the hospital with concern for infection but only five (45%)
      patients had actual infections and received additional treatment. In comparison,
      in the post-protocol cohort, 11 patients were admitted for suspected infection,
      nine (82%) of whom were truly infected (p = 0.04). Sensitivity increased from 83%
      to 100% and specificity increased from 71% to 96%. Implementation of this
      protocol did not miss any infections. CONCLUSION: A standardised protocol for
      evaluation of THA and TKA infections significantly reduced unnecessary hospital
      re-admissions. The protocol was both sensitive and specific and did not
      compromise quality of care. Cite this article: Bone Joint J 2017;99-B:1603-10.

PMID- 29212684
TI  - Do higher-volume hospitals provide better value in revision hip and knee
      arthroplasty?
AB  - AIMS: The purpose of this study is to determine if higher volume hospitals have
      lower costs in revision hip and knee arthroplasty. MATERIALS AND METHODS: We
      questioned the Centres for Medicare and Medicaid Services (CMS) Inpatient Charge
      Data and identified 789 hospitals performing a total of 29 580 revision
      arthroplasties in 2014. Centres were dichotomised into high-volume (performing
      over 50 revision cases per year) and low-volume. Mean total hospital-specific
      charges and inpatient payments were obtained from the database and stratified
      based on Diagnosis Related Group (DRG) codes. Patient satisfaction scores were
      obtained from the multiyear CMS Hospital Compare database. RESULTS: High-volume
      hospitals comprised 178 (30%) of the total but performed 15 068 (51%) of all
      revision cases, including 509 of 522 (98%) of the most complex DRG 466 cases.
      While high-volume hospitals had higher Medicare inpatient payments for DRG 467
      ($21 458 versus $20 632, p = 0.038) and DRG 468 ($17 003 versus $16 120, p =
      0.011), there was no difference in hospital specific charges between the groups.
      Higher-volume facilities had a better CMS hospital star rating (3.63 versus 3.35,
      p < 0.001). When controlling for hospital geographic and demographic factors,
      high-volume revision hospitals are less likely to be in the upper quartile of
      inpatient Medicare costs for DRG 467 (odds ratio (OR) 0.593, 95% confidence
      intervals (CI) 0.374 to 0.941, p = 0.026) and DRG 468 (OR 0.451, 95% CI 0.297 to
      0.687, p < 0.001). CONCLUSION: While a high-volume hospital is less likely to be
      a high cost outlier, the higher mean Medicare reimbursements at these facilities
      may be due to increased case complexity. Further study should focus on measures
      for cost savings in revision total joint arthroplasties. Cite this article: Bone
      Joint J 2017;99-B:1611-17.

PMID- 29212685
TI  - An analysis of 30-day mortality after weekend versus weekday elective joint
      arthroplasty in England and Wales: a cohort study using the National Joint
      Registry Dataset.
AB  - AIMS: To investigate whether elective joint arthroplasty performed at the weekend
      is associated with a different 30-day mortality versus that performed between
      Monday and Friday. PATIENTS AND METHODS: We examined the 30-day cumulative
      mortality rate (Kaplan-Meier) for all elective hip and knee arthroplasties
      performed in England and Wales between 1st April 2003 and 31st December 2014,
      comprising 118 096 episodes undertaken at the weekend and 1 233 882 episodes
      performed on a weekday. We used Cox proportional-hazards regression models to
      assess for time-dependent variation and adjusted for identified risk factors for
      mortality. RESULTS: The cumulative 30-day mortality for hip arthroplasty was
      0.15% (95% confidence interval (CI) 0.12 to 0.19) for patients operated on at the
      weekend versus 0.20% (95% CI 0.19 to 0.21) for patients undergoing surgery during
      the normal working week. For knee arthroplasty, the cumulative 30-day mortality
      was 0.14% (95% CI 0.11 to 0.17) for weekend-operated patients versus 0.18% (95%
      CI 0.17 to 0.19) for weekday-operated patients. These differences were
      independent of any differences in patient age, gender, American Society of
      Anaesthesiologists grade, surgeon seniority, surgical and anaesthetic practices,
      and thromboprophylaxis choice in weekend versus weekday-operated patients.
      CONCLUSION: The 30-day mortality rate after elective joint arthroplasty is low.
      Surgery performed at the weekend is associated with lower post-operative
      mortality versus operations performed on a weekday. Cite this article: Bone Joint
      J 2017;99-B:1618-28.

PMID- 29212686
TI  - Practice patterns in the care of acute Achilles tendon ruptures : is there an
      association with level I evidence?
AB  - AIMS: To determine whether the findings from a landmark Canadian trial assessing
      the optimal management of acute rupture of the Achilles tendon influenced the
      practice patterns of orthopaedic surgeons in Ontario, Canada. MATERIALS AND
      METHODS: Health administrative databases were used to identify Ontario residents
      >= 18 years of age with an Achilles tendon rupture from April 2002 to March 2014.
      The rate of surgical repair (per 100 cases) was calculated for each calendar
      quarter. A time-series analysis was used to determine whether changes in the rate
      were chronologically related to the dissemination of results from a landmark
      trial published in February 2009. Non-linear spline regression was then used
      independently to identify critical time-points of change in the surgical repair
      rate to confirm the findings. RESULTS: A total of 29 531 patients sustained an
      Achilles tendon rupture during the study period. Consistently, around 21 out of
      every 100 cases underwent surgical repair up to the first quarter of 2010.
      However, by the first quarter of 2014, only 6.5 cases per 100 had surgery. A
      statistically significant decrease in the rate of surgical repair was observed
      within one year of the presentation of landmark trial results in 2009 (p <
      0.001). July 2009 was independently identified as a critical time at which the
      surgical repair rate began to significantly decline (p < 0.001). The
      dissemination of trial results was associated with a significant drop in the rate
      of surgical repair at non-teaching hospitals (p = 0.001). CONCLUSION: The current
      study demonstrates that large, well-designed randomised trials, have the
      potential to encourage significant changes in the practice patterns of
      orthopaedic surgeons. Cite this article: Bone Joint J 2017;99-B:1629-36.

PMID- 29212687
TI  - Comparative study on the effectiveness of a corticosteroid injection for carpal
      tunnel syndrome in patients with and without Raynaud's phenomenon.
AB  - AIMS: The aim of this study was to compare the efficacy of a corticosteroid
      injection for the treatment of carpal tunnel syndrome (CTS) in patients with and
      without Raynaud's phenomenon. PATIENTS AND METHODS: In a prospective study, 139
      patients with CTS were treated with a corticosteroid injection (10 mg
      triamcinolone acetonide); 34 had Raynaud's phenomenon and 105 did not (control
      group). Grip strength, perception of touch with a Semmes-Weinstein monofilament
      and the Boston Carpal Tunnel Questionnaires (BCTQ) were assessed at baseline and
      at six, 12 and 24 weeks after the injection. The Cold Intolerance Severity Score
      (CISS) questionnaire was also assessed at baseline and 24 weeks after the
      injection. RESULTS: The two groups had similar baseline BCTQ scores, but the
      scores in the Raynaud's phenomenon group were significantly higher than those in
      the control group at 12 and 24 weeks after the injection. Throughout the 24-week
      follow-up, there were no significant differences in the mean grip strength
      between the groups, whereas the mean Semmes-Weinstein monofilament sensory index
      for the control group was significantly higher than that of the Raynaud's
      phenomenon group. The mean CISSs were not significantly different between the
      groups at baseline and at 24 weeks. After 24 weeks, 11 patients (32%) in the
      Raynaud's phenomenon group and 16 (15%) in the control group required carpal
      tunnel decompression (p = 0.028). Multivariable analysis indicated that
      concurrent Raynaud's phenomenon (odds ratio (OR) 2.6) and severe
      electrophysiological grade (OR 2.1) were independently associated with a failure
      of treatment after a corticosteroid injection. CONCLUSION: Although considerable
      improvements in symptoms will probably occur in patients with Raynaud's
      phenomenon who have CTS, they have higher risk of poor functional outcomes and
      failure of treatment than those without Raynaud's phenomenon. Cite this article:
      Bone Joint J 2017;99-B:1637-42.

PMID- 29212688
TI  - Prognostic factors for the outcome of extracorporeal shockwave therapy for
      calcific tendinitis of the shoulder.
AB  - AIMS: We conducted a study to identify factors that are prognostic of the outcome
      of extracorporeal shockwave therapy (ESWT) for calcific tendinitis of the
      shoulder. PATIENTS AND METHODS: Since 1998, patients with symptomatic calcific
      tendinitis of the rotator cuff have been treated with ESWT using an
      electrohydraulic mode shockwave device. One year after ESWT, patients were
      grouped according to the level of resorption of calcification. RESULTS: Of 241
      symptomatic shoulders, complete resorption (CR) of calcification occurred in 134
      (CR group). The remaining 107 shoulders had incomplete resorption (ICR) (ICR
      group). Gartner type I calcification was most common (64.5%) in the ICR group.
      The mean duration of symptoms before ESWT was significantly longer in the ICR
      group. Overall, 81% of the CR group and 23.4% of the ICR group were symptom free.
      There was a strong relationship between subsidence of symptoms and remission of
      calcification. Poor prognosis was significantly related to Gartner type I
      calcification, calcification extent > 15 mm and duration of symptoms > 11 months.
      CONCLUSION: Patients with calcific tendinitis of the shoulder who have the
      factors identified for a poor outcome after ESWT should undergo a different
      procedure. Cite this article: Bone Joint J 2017;99-B:1643-50.

PMID- 29212689
TI  - Minimally invasive surgery for adolescent idiopathic scoliosis: correction of
      deformity and peri-operative morbidity in 70 consecutive patients.
AB  - AIMS: The aim of this study was to report a retrospective, consecutive series of
      patients with adolescent idiopathic scoliosis (AIS) who were treated with
      posterior minimally invasive surgery (MIS) with a mean follow-up of two years (sd
      1.4; 0.9 to 0 3.7). Our objectives were to measure the correction of the
      deformity and record the peri-operative morbidity. Special attention was paid to
      the operating time (ORT), estimated blood loss (EBL), length of stay (LOS) and
      further complications. PATIENTS AND METHODS: We prospectively collected the data
      of 70 consecutive patients with AIS treated with MIS using three incisions and a
      muscle-splitting approach by a single surgeon between June 2013 and February 2016
      and these were retrospectively reviewed. There were eight male and 62 female
      patients with a mean age of 15 years (sd 4.5 ) with a mean body mass index of
      19.8 kg/m2 (sd 5.4). The curves were classified according to Lenke; 40 curves
      were type 1, 15 were type 2, three were type 3, two were type 4, eight were type
      5 and two were type 6. RESULTS: The mean primary Cobb angle was corrected from
      58.9 degrees  (sd 12.6 degrees ) pre-operatively to 17.7 degrees  (sd 10.2
      degrees ) post-operatively with a mean correction of 69% (sd 20%, p < 0.001). The
      mean kyphosis at T5 to T12 increased from 24.2 degrees  (sd 12.2 degrees ) pre
      operatively to 30.1 degrees  (sd 9.6 degrees , p < 0.001) post-operatively. Peri
      operative (30 days) complications occurred in three patients(4.2%): one
      subcutaneous haematoma, one deep venous thrombosis and one pulmonary
      complication. Five additional complications occurred in five patients (7.1%): one
      superficial wound infection, one suture granuloma and three delayed deep surgical
      site infections. The mean ORT was 337.1 mins (sd 121.3); the mean EBL was 345.7
      ml (sd 175.1) and the mean LOS was 4.6 days (sd 0.8). CONCLUSION: The use of MIS
      for patients with AIS results in a significant correction of spinal deformity in
      both the frontal and sagittal planes, with a low EBL and a short LOS. The rate of
      peri-operative complications compares well with that following a routine open
      technique. The longer term safety and benefit of MIS in these patients needs to
      be evaluated with further follow-up of a larger cohort of patients. Cite this
      article: Bone Joint J 2017;99-B:1651-7.

PMID- 29212690
TI  - Quantifying the 'law of diminishing returns' in magnetically controlled growing
      rods.
AB  - AIMS: Magnetically controlled growing rods (MCGRs) allow non-invasive correction
      of the spinal deformity in the treatment of early-onset scoliosis. Conventional
      growing rod systems (CGRS) need repeated surgical distractions: these are
      associated with the effect of the 'law of diminishing returns'. The primary aim
      of this study was to quantify this effect in MCGRs over sequential distractions.
      PATIENTS AND METHODS: A total of 35 patients with a maximum follow-up of 57
      months were included in the study. There were 17 boys and 18 girls with a mean
      age of 7.4 years (2 to 14). True Distraction (TD) was determined by measuring the
      expansion gap on fluoroscopy. This was compared with Intended Distraction (ID)
      and expressed as the 'T/I' ratio. The T/I ratio and the Cobb angle were
      calculated at several time points during follow-up. RESULTS: The mean follow-up
      was 30 months (6 to 57). There was a significant decrease in the mean T/I ratio
      over time (convex rod at 3 months 0.81, sd 0.58 vs 51 months 0.17, sd 0.16, p =
      0.0001; concave rod at 3 months 0.93, sd 0.67 vs 51 months 0.18, sd 0.15, p =
      0.0001). A linear decline of the mean T/I ratios was noted for both convex rods
      (r2 = 0.90, p = 0.004) and concave rods (r2 = 0.81, p = 0.015) over 51 months. At
      the 24-month follow-up stage, there was a significant negative correlation
      between the mean T/I ratio of the concave rod with weight (r = -0.59, p = 0.01),
      age (r = -0.59, p = 0.01), and BMI of the child (r = -0.54, p = 0.01).
      CONCLUSIONS: The 'law of diminishing returns' is also seen after serial
      distraction using MCGR. Compared to previously published data for CGRS, there is
      a gradual linear decline rather than a rapid initial decline in lengthening. In
      older, heavier children a reduced distraction ratio in the concave rod of the
      MCGR device is noted over time. Cite this article: Bone Joint J 2017;99-B:1658
      64.

PMID- 29212691
TI  - Longitudinal recovery following distal radial fractures managed with volar plate
      fixation.
AB  - AIMS: To synthesise the literature and perform a meta-analysis detailing the
      longitudinal recovery in the first two years following a distal radius fracture
      (DRF) managed with volar plate fixation. MATERIALS AND METHODS: Three databases
      were searched to identify relevant articles. Following eligibility screening and
      quality assessment, data were extracted and outcomes were assimilated at the post
      operative time points of interest. A state-of-the-art longitudinal mixed-effects
      meta-analysis model was employed to analyse the data. RESULTS: The search
      identified 5698 articles, of which 46 study reports met the selection criteria.
      High levels of disability and impairment were reported in the immediate post
      operative period with subsequently a rapid initial improvement followed by more
      gradual improvement for up to one year. The results highlight that the period
      associated with the greatest physical recovery is in the first three months and
      suggest that the endpoint of treatment outcomes is best measured at one year post
      surgery. CONCLUSION: Clinically meaningful improvements in outcomes can be
      expected for 12 months, after which progress plateaus and reaches normal values.
      This paper adopted a novel approach to meta-analyses in that the research
      question was of a longitudinal nature, which required a unique method of
      statistical analysis. Cite this article: Bone Joint J 2017;99-B:1665-76.

PMID- 29212692
TI  - The impact of age on major orthopaedic trauma: an analysis of the United Kingdom
      Trauma Audit Research Network database.
AB  - AIMS: To compare the early management and mortality of older patients sustaining
      major orthopaedic trauma with that of a younger population with similar injuries.
      PATIENTS AND METHODS: The Trauma Audit Research Network database was reviewed to
      identify eligible patients admitted between April 2012 and June 2015.
      Distribution and severity of injury, interventions, comorbidity, critical care
      episodes and mortality were recorded. The population was divided into young (64
      years or younger) and older (65 years and older) patients. RESULTS: Of 142 765
      adults sustaining major trauma, 72 942 (51.09 %) had long bone or pelvic
      fractures and 45.81% of these were > 65 years old. Road traffic collision was the
      most common mechanism in the young (40.4%) and, in older people, fall from
      standing height (80.4%) predominated. The 30 day mortality in older patients with
      fractures is greater (6.8% versus 2.5%), although critical care episodes are more
      common in the young (18.2% versus 9.7%). Older people are less likely to be
      admitted to critical care beds and are often managed in isolation by surgeons.
      Orthopaedic surgery is the most common admitting and operating specialty and, in
      older people, fracture surgery accounted for 82.1% of procedures. CONCLUSION:
      Orthopaedic trauma in older people is associated with mortality that is
      significantly greater than for similar fractures in the young. As with the hip
      fracture population, major trauma in the elderly is a growing concern which
      highlights the need for a review of admission pathways and shared orthogeriatric
      care models. Cite this article: Bone Joint J 2017;99-B:1677-80.

PMID- 29212693
TI  - Clinical, functional and radiological outcomes of extracorporeal irradiation in
      limb salvage surgery for bone tumours.
AB  - AIMS: We present a retrospective review of patients treated with extracorporeally
      irradiated allografts for primary and secondary bone tumours with the mid- and
      long-term survivorship and the functional and radiographic outcomes. PATIENTS AND
      METHODS: A total of 113 of 116 (97.4%) patients who were treated with
      extracorporeally irradiated allografts between 1996 and 2014 were followed up.
      Forms of treatment included reconstructions, prostheses and composite
      reconstructions, both with and without vascularised grafts. Survivorship was
      determined by the Kaplan-Meier method. Clinical outcomes were assessed using the
      Musculoskeletal Tumor Society (MSTS) scoring system, the Toronto Extremity
      Salvage Score (TESS) and Quality of Life-C30 (QLQ-30) measures. Radiographic
      outcomes were assessed using the International Society of Limb Salvage (ISOLS)
      radiographic scoring system. RESULTS: There were 61 (54%) men with a mean age of
      22 years (6 to 70) and 52 (46%) women with a mean age of 26 years (3 to 85).
      There were 23 deaths. The five-year patient survivorship was 82.3% and the ten
      year patient survivorship was 79.6%. The mean follow-up of the 90 surviving
      patients was 80.3 months (2 to 207). At the last follow-up, 105 allografts
      (92.9%) were still in place or had been at the time of death; eight (7%) had
      failed due to infection, local recurrence or fracture. Outcome scores were
      comparable with or superior to those in previous studies. The mean outcome scores
      were: MSTS 79% (sd 8); TESS 83% (sd 19); QLQ 82% (sd 16); ISOLS 80.5% (sd 19).
      Pearson correlation analysis showed a strong relationship between the MSTS and
      ISOLS scores (r = 0.71, p < 0.001). CONCLUSION: This study shows that
      extracorporeal irradiation is a versatile reconstructive technique for dealing
      with large defects after the resection of bone tumours with good functional and
      radiographic outcomes. Functional outcomes as measured by MSTS, TESS and QLQ-30
      were strongly correlated to radiographic outcomes. Cite this article: Bone Joint
      J 2017;99-B:1681-8.

PMID- 29212694
TI  - Minimising aseptic loosening in extreme bone resections: custom-made tumour
      endoprostheses with short medullary stems and extra-cortical plates.
AB  - AIMS: Following the resection of an extensive amount of bone in the treatment of
      a tumour, the residual segment may be insufficient to accept a standard length
      intramedullary cemented stem. Short-stemmed endoprostheses conceivably have an
      increased risk of aseptic loosening. Extra-cortical plates have been added to
      minimise this risk by supplementing fixation. The aim of this study was to
      investigate the survivorship of short-stemmed endoprostheses and extra-cortical
      plates. PATIENTS AND METHODS: The study involved 37 patients who underwent limb
      salvage surgery for a primary neoplasm of bone between 1998 and 2013.
      Endoprosthetic replacement involved the proximal humerus in nine, the proximal
      femur in nine, the distal femur in 13 and the proximal tibia in six patients.
      There were 12 primary (32%) and 25 revision procedures (68%). Implant
      survivorship was compared with matched controls. The amount of bone that was
      resected was > 70% of its length and statistically greater than the standard
      control group at each anatomical site. RESULTS: The mean follow-up was seven
      years (one to 17). The mean length of the stem was 33 mm (20 to 60) in the
      humerus and 79 mm (34 to 100) in the lower limb. Kaplan-Meier analysis of
      survival of the implant according to anatomical site confirmed that there was no
      statistically significant difference between the short-stemmed endoprostheses and
      the standard stemmed controls at the proximal humeral (p = 0.84), proximal
      femoral (p = 0.57), distal femoral (p = 0.21) and proximal tibial (p = 0.61)
      sites. In the short-stemmed group, no implants with extra-cortical plate
      osseointegration suffered loosening at a mean of 8.5 years (range 2 to 16 years).
      Three of ten (30%) without osseointegration suffered aseptic loosening at a mean
      of 7.7 years (range 2 to 11.5 years). CONCLUSION: When extensive resections of
      bone are required in the surgical management of tumours, and in revision cases,
      the addition of extra-cortical plates to short medullary stems has shown non
      inferiority to standard length medullary stems and minimises aseptic failure.
      Cite this article: Bone Joint J 2017;99-B:1689-95.

PMID- 29212695
TI  - Corrigendum.
AB  - Mohaddes M, Shareghi B, Karrholm J. Promising early results for trabecular metal
      acetabular components used at revision total hip arthroplasty. Bone Joint J
      2017;99-B:880-886.

PMID- 29212696
TI  - Corrigendum.
AB  - Wall PDH, Parsons NR, Parsons H, Achten J, Balasubramanian S, Thompson P, Costa
      ML; P. D. H. Wall on behalf of A. P. Sprowson,? M. L. Costa, PAKA Study Group. A
      pragmatic randomised controlled trial comparing the efficacy of a femoral nerve
      block and periarticular infiltration for early pain relief following total knee
      arthroplasty. Bone Joint J 2017;99-B:904-911.

PMID- 29212697
TI  - Errata.
AB  - Stavem K, Naumann MG, Sigurdsen U, Utvag SE. The association of body mass index
      with complications and functional outcomes after surgery for closed ankle
      fractures. Bone Joint J 2017;99-B:1389-1398.

PMID- 29212698
TI  - Corrigendum.
AB  - Refaie R, Rushton PRP, McGovern PD, Thompson D, Serrano-Pedraza I, Rankin KS,
      Reed MR. The effect of operating lights on laminar flow: an experimental study
      using neutrally buoyant helium bubbles. Bone Joint J 2017;99-B:1061-1066.

PMID- 29212700
TI  - The Alere BinaxNOW Pneumococcal Urinary Antigen Test: Diagnostic Sensitivity for
      Adult Pneumococcal Pneumonia and Relationship to Specific Serotypes.
AB  - Little is known about the sensitivity of the BinaxNOW pneumococcal urinary
      antigen (PUA) test for adult pneumococcal pneumonia caused by different
      serotypes. In this study, we aimed to analyze the trends in the sensitivity of
      the PUA test over a 15-year period (2001 to 2015) and to analyze its sensitivity
      for pneumococcal pneumonia caused by different serotypes. In total, we analyzed
      1,096 pneumococcal isolates from adults with pneumococcal pneumonia who had a PUA
      test performed at the onset of the episode. Three periods were analyzed: 2001 to
      2005 (early use of the seven-valent pneumococcal conjugate vaccine [early PCV7]),
      2006 to 2010 (late PCV7), and 2011 to 2015 (early PCV13). The sensitivity of the
      PUA test varied from 76.4% (95% confidence interval [CI], 70.5% to 82.4%) in the
      period from 2001 to 2005 to 77.9% in 2006 to 2010 (95% CI, 74.4% to 81.4%) and
      decreased to 60.5% (95% CI, 55.4% to 65.6%) in 2011 to 2015. This decrease was
      observed in 560 proven (83.2% in 2001 to 2005, 86.5% in 2006 to 2010, and 78.1%)
      and 536 probable (70.0% in 2001 to 2005, 68.7% in 2006 to 2010, and 41.5% in 2011
      to 2015) episodes of pneumococcal pneumonia. Differences were observed in the
      sensitivity of the PUA test for diagnosing pneumonia caused by certain serotypes,
      being highest for the 9V (90.6%), 14 (86.8%), 18C (100%), and 20 (100%) serotypes
      and lowest for the 8 (55.2%), 9L/N (39.1%), 11A (48.8%), 23B (33.3%), and
      nontypeable (47.8%) serotypes. Comparing 2001 to 2005, 2006 to 2010, and 2011 to
      2015, the prevalence of serotypes 9V (3.1%, 3.7%, and 1.7%, respectively) and 14
      (7.2%, 5.1%, and 3.1%, respectively) decreased, while the prevalence of serotypes
      23B (0%, 0.7%, and 1.4%, respectively), 9L/N (1.0%, 1.6%, and 3.4%,
      respectively), 11A (2.6%, 4.2%, and 3.7%, respectively), and 8 (1.5%, 1.5%, and
      5.1%, respectively) increased. The PUA test sensitivity varied by pneumococcal
      pneumonia serotype, and these differences and the changes in serotype
      distribution were associated with an overall decrease in the sensitivity of the
      PUA test.

PMID- 29212699
TI  - Rapid Microarray-Based Detection of Rifampin, Isoniazid, and Fluoroquinolone
      Resistance in Mycobacterium tuberculosis by Use of a Single Cartridge.
AB  - The rapid and robust identification of mutations in Mycobacterium tuberculosis
      complex (MTBC) strains mediating multidrug-resistant (MDR) and extensively drug
      resistant (XDR) phenotypes is crucial to combating the MDR tuberculosis (TB)
      epidemic. Currently available molecular anti-TB drug susceptibility tests either
      are restricted to a single target or drug (i.e., the Xpert MTB/RIF test) or
      present a risk of cross-contamination due to the design limitations of the open
      platform (i.e., line probe assays). With a good understanding of the technical
      and commercial boundaries, we designed a test cartridge based on an
      oligonucleotide array into which dried reagents are introduced and which has the
      ability to identify MTBC strains resistant to isoniazid, rifampin, and the
      fluoroquinolones. The melting curve assay interrogates 43 different mutations in
      the rifampin resistance-determining region (RRDR) of rpoB, rpoB codon 572, katG
      codon 315, the inhA promoter region, and the quinolone resistance-determining
      region (QRDR) of gyrA in a closed cartridge system within 90 min. Assay
      performance was evaluated with 265 clinical MTBC isolates, including MDR/XDR, non
      MDR, and fully susceptible isolates, from a drug resistance survey performed in
      Swaziland in 2009 and 2010. In 99.5% of the cases, the results were consistent
      with data previously acquired utilizing Sanger sequencing. The assay, which uses
      a closed cartridge system in combination with a battery-powered Alere q analyzer
      and which has the potential to extend the current gene target panel, could serve
      as a rapid and robust point-of-care test in settings lacking a comprehensive
      molecular laboratory infrastructure to differentiate TB patients infected with
      MDR and non-MDR strains and to assist clinicians with their early treatment
      decisions.

PMID- 29212701
TI  - Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection
      of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs.
AB  - The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark
      Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus;
      influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza
      B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human
      rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and
      4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2
      bacteria (Mycoplasma pneumoniae and Chlamydia pneumoniae) was evaluated.
      Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens
      (n = 2,908) were evaluated by using the ePlex RP panel, with the
      bioMerieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator
      method. Discordance analysis was performed by using target-specific PCRs and
      bidirectional sequencing. The reproducibility of the assay was evaluated by using
      reproducibility panels comprised of 6 pathogens. The overall agreement between
      the ePlex RP and BioFire RP results was >95% for all targets. Positive percent
      agreement with the BioFire RP result for viruses ranged from 85.1% (95%
      confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%),
      while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to
      99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant
      targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of
      samples tested. Reproducibility was 100% for all targets tested, with the
      exception of adenovirus, for which reproducibilities were 91.6% at low virus
      concentrations and 100% at moderate virus concentrations. The ePlex RP panel
      offers a new, rapid, and sensitive "sample-to-answer" multiplex panel for the
      detection of the most common viral and bacterial respiratory pathogens.

PMID- 29212702
TI  - Multicenter Clinical Validation of a Cartridge-Based Real-Time PCR System for
      Detection of Coccidioides spp. in Lower Respiratory Specimens.
AB  - Available methods for the diagnosis of coccidioidomycosis have significant
      shortcomings relative to accuracy and timeliness. We retrospectively and
      prospectively evaluated the diagnostic performance and reproducibility of a new
      cartridge-based real-time PCR assay for Coccidioides spp. directly in lower
      respiratory secretions and compared them to today's "gold standard," fungal
      culture. The GeneSTAT Coccidioides assay uses a 106-bp target sequence repeated
      multiple times (~60*) per genome, thus lowering the limit of detection (LOD) for
      extracted DNA to 10 genome equivalents/ml. A total of 332 prospective and
      retrospective individual patient specimens were tested. The retrospective samples
      consisted of 100 bronchoalveolar lavage or bronchial wash (BAL/BW) (51 positive
      and 49 negative by culture) specimens that had been collected previously and
      stored at -70 degrees C. These samples were tested by the GeneSTAT Coccidioides
      assay across three clinical test sites. The sensitivity was 100%, and the
      specificity ranged between 93.8% and 100%. There was minimal variance in the
      percent agreement across the three sites, 95.6% to 100%. Additionally, a total of
      232 fresh (prospective) deidentified BAL/BW specimens were tested across the
      three clinical sites, which included a number of specimens from Southern
      California to provide a diversity of isolates. Specimens were tested by fungal
      culture, with any isolates of Coccidioides, except for one, being confirmed by
      molecular means (AccuProbe). The sensitivity of the GeneSTAT Coccidioides assay
      across the three sites was 100% (4/4) for positive fresh specimens, and the
      overall specificity of the assay was 99.6% (227/228), ranging from 98.1% to 100%.
      In testing for cross-reactivity, the assay was 100% specific when screened
      against 47 different bacterial, viral, and fungal species.

PMID- 29212703
TI  - Diagnostic Assay Development for Poliovirus Eradication.
AB  - With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV)
      transmission remain in the world. Intratypic differentiation (ITD) plays a
      crucial part in laboratory surveillance as the molecular detection method that
      can identify and distinguish wild and vaccine-like polioviruses isolated from
      acute flaccid paralysis cases or environmental sources. The need to detect new
      variants of WPV serotype 1 (WPV1) and the containment of all serotype 2
      polioviruses (PV2) in 2015 required changes to the previous version of the
      method. The ITD version 5.0 is a set of six real-time reverse transcription-PCR
      (rRT-PCR) assays that serve as accurate diagnostic tools to easily detect and
      differentiate PV serotypes and genotypes. We describe the creation and properties
      of quantitation standards, including 16 control RNA transcripts and nine plaque
      isolated viruses. All ITD rRT-PCR assays were validated using these standards,
      and the limits of detection were determined for each assay. We designed and pilot
      tested two new assays targeting recently circulating WPV1 genotypes and all PV2
      viruses. The WPV1 assay had 99.1% specificity and 100% sensitivity, and the PV2
      assay had 97.7% specificity and 92% sensitivity. Before proceeding to the next
      step in the global poliovirus eradication program, we needed to gain a better
      understanding of the performance of the ITD 5.0 suite of molecular assays and
      their limits of detection and specificities. The findings and conclusions in this
      evaluation serve as building blocks for future development work.

PMID- 29212704
TI  - Performance of Ceftolozane-Tazobactam Etest, MIC Test Strips, and Disk Diffusion
      Compared to Reference Broth Microdilution for beta-Lactam-Resistant Pseudomonas
      aeruginosa Isolates.
AB  - The performance characteristics of the ceftolozane-tazobactam (C-T) Etest
      (bioMerieux, Marcy l'Etoile, France), MIC test strips (MTS; Liofilchem, Italy),
      and disk diffusion (Hardy, Santa Ana, CA) were evaluated for a collection of 308
      beta-lactam-resistant isolates of Pseudomonas aeruginosa recovered from three
      institutions in Los Angeles, CA. Reference testing was performed by the reference
      broth microdilution (rBMD) method. MIC and disk results were interpreted using
      Clinical and Laboratory Standards Institute breakpoints. Overall, 72.5% of the
      isolates were susceptible to C-T by rBMD. Etest and disk diffusion demonstrated
      acceptable performance, whereas MTS yielded a greater than acceptable percentage
      of minor errors. Categorical agreement was 96.8% for Etest, 87.0% for MTS, and
      92.9% for disk diffusion. No very major errors were observed by any test, and no
      major errors (ME) were observed by Etest or disk diffusion. Two ME (0.9% of
      susceptible isolates) were observed by MTS. The incidence of minor errors was
      3.2%, 12.3%, and 7.1% for Etest, MTS, and disk diffusion, respectively. Essential
      agreement (EA) for Etest was excellent, at 97.7%, whereas the MICs obtained by
      MTS tended to be 1 to 2 dilutions higher than those obtained by rBMD, with an EA
      of 87.0%.

PMID- 29212705
TI  - Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and
      Acquired Resistance Causes Concern.
AB  - New data from the years 2012 to 2015 from the Danish National Fungemia
      Surveillance are reported, and epidemiological trends are investigated in a 12
      year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal
      bloodstream isolates were included. The average incidence was 8.4/100,000
      inhabitants, and this appears to represent a stabilizing trend after the increase
      to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0
      versus 6.8) and in patients above 50 years, and those changes were mainly driven
      by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to
      2015). The proportion of Candida albicans isolates decreased from 2004 to 2015
      (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida
      glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among
      females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the
      annual drug use stabilized during the last 2 to 3 years of that time period but
      remained higher than in other Nordic countries. This was particularly true for
      the fluconazole and itraconazole use in the primary health care sector, which
      exceeded the combined national levels of use of these compounds in each of the
      other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and
      60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001),
      and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively,
      P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%)
      echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS
      mutations and 5 (31%) were multidrug resistant. The epidemiological changes and
      the increased incidence of intrinsic and acquired resistance emphasize the
      importance of continued surveillance and of strengthened focus on antifungal
      stewardship.

PMID- 29212706
TI  - Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its
      cognate E2 ubiquitin ligase.
AB  - Heightened and extended inflammation underlies the pathogenesis of many
      disorders, including inflammatory bowel disease, sepsis, and inflammatory
      arthritis. Ubiquitin networks help dictate the strength and duration of
      inflammatory signaling. In innate immunity, the itchy E3 ubiquitin protein ligase
      (ITCH)-A20 ubiquitin-editing complex inhibits receptor-interacting Ser/Thr kinase
      (RIPK) activation by removing Lys-63-linked polyubiquitinated chains from key
      proteins in the nuclear factor kappa B (NF-kappaB) signaling pathway. The complex
      then attaches polyubiquitinated chains to these proteins to target them for
      lysosomal or proteasomal destruction. ITCH is phosphorylated and thereby
      inhibited by inhibitor of nuclear factor kappa B kinase subunit beta (IKKbeta) to
      fine-tune the inflammatory response to the strength of the offending signal.
      However, the biochemical mechanism by which E3 ubiquitination is impaired by IKK
      driven phosphorylation remains unclear. Here, we report that this phosphorylation
      impedes ITCH binding to its cognate E2 ubiquitin ligase, UbcH7. Using CRISPR-Cas9
      genetic knockout to mimic the ITCH-UbcH7-inhibited state, we further show that
      genetic UbcH7 deficiency phenocopies ITCH phosphorylation in regulating RIPK2
      ubiquitination. We conclude that phosphorylation can disrupt the binding of an E3
      ubiquitin ligase to an E2-conjugating enzyme, leading to prolonged inflammatory
      signaling. To our knowledge, this is the first report of E3 ubiquitin ligase
      phosphorylation inhibiting E3 ligase activity by impairing E2-E3 complex
      formation.

PMID- 29212707
TI  - Inherent steroid 17alpha,20-lyase activity in defunct cytochrome P450 17A
      enzymes.
AB  - Cytochrome P450 (P450) 17A1 catalyzes the oxidations of progesterone and
      pregnenolone and is the major source of androgens. The enzyme catalyzes both
      17alpha-hydroxylation and a subsequent 17alpha,20-lyase reaction, and several
      mechanisms have been proposed for the latter step. Zebrafish P450 17A2 catalyzes
      only the 17alpha-hydroxylations. We previously reported high similarity of the
      crystal structures of zebrafish P450 17A1 and 17A2 and human P450 17A1. Five
      residues near the heme, which differed, were changed. We also crystallized this
      five-residue zebrafish P450 17A1 mutant, and the active site still resembled the
      structure in the other proteins, with some important differences. These P450 17A1
      and 17A2 mutants had catalytic profiles more similar to each other than did the
      wildtype proteins. Docking with these structures can explain several minor
      products, which require multiple enzyme conformations. The 17alpha-hydroperoxy
      (OOH) derivatives of the steroids were used as oxygen surrogates. Human P450 17A1
      and zebrafish P450s 17A1 and P450 17A2 readily converted these to the lyase
      products in the absence of other proteins or cofactors (with catalytically
      competent kinetics) plus hydroxylated 17alpha-hydroxysteroids. The 17alpha-OOH
      results indicate that a "Compound I" (FeO3+) intermediate is capable of formation
      and can be used to rationalize the products. We conclude that zebrafish P450 17A2
      is capable of lyase activity with the 17alpha-OOH steroids because it can achieve
      an appropriate conformation for lyase catalysis in this system that is precluded
      in the conventional reaction.

PMID- 29212708
TI  - The crystal structure of pseudokinase PEAK1 (Sugen kinase 269) reveals an unusual
      catalytic cleft and a novel mode of kinase fold dimerization.
AB  - The pseudokinase group encompasses some 10% of protein kinases, but pseudokinases
      diverge from canonical kinases in key motifs. The two members of the small new
      kinase family 3 (NKF3) group are considered pseudokinases. These proteins,
      pseudopodium-enriched atypical kinase 1 (PEAK1, Sugen kinase 269, or SgK269) and
      pragmin (Sugen kinase 223 or SgK223), act as scaffolds in growth factor signaling
      pathways, and both contain a kinase fold with degraded kinase motifs at their C
      termini. These kinases may harbor regions that mediate oligomerization or control
      other aspects of signal transduction, but a lack of structural information has
      precluded detailed investigations into their functional roles. In this study, we
      determined the X-ray crystal structure of the PEAK1 pseudokinase domain to 2.3 A
      resolution. The structure revealed that the PEAK1 kinase-like domain contains a
      closed nucleotide-binding cleft that in this conformation may deleteriously
      affect nucleotide binding. Moreover, we found that N- and C-terminal extensions
      create a highly unusual all alpha-helical split-dimerization region, termed here
      the split helical dimerization (SHED) region. Sequence conservation analysis
      suggested that this region facilitates a dimerization mode that is conserved
      between PEAK1 and pragmin. Finally, we observed structural similarities between
      the PEAK1 SHED region and the C-terminal extension of the Parkinson's disease
      associated kinase PINK1. In summary, PEAK1's kinase cleft is occluded, and its
      newly identified SHED region may promote an unexpected dimerization mode.
      Similarities of PEAK1 with the active kinase PINK1 may reclassify the latter as a
      member of the new kinase family 3 group.

PMID- 29212710
TI  - Clinical trial design: The nobility of randomization.
AB  - A clinical trial evaluating HIV vaccine therapy teaches us much about optimal
      design (Sneller et al, this issue).

PMID- 29212709
TI  - A eukaryotic nicotinate-inducible gene cluster: convergent evolution in fungi and
      bacteria.
AB  - Nicotinate degradation has hitherto been elucidated only in bacteria. In the
      ascomycete Aspergillus nidulans, six loci, hxnS/AN9178 encoding the molybdenum
      cofactor-containing nicotinate hydroxylase, AN11197 encoding a Cys2/His2 zinc
      finger regulator HxnR, together with AN11196/hxnZ, AN11188/hxnY, AN11189/hxnP and
      AN9177/hxnT, are clustered and stringently co-induced by a nicotinate derivative
      and subject to nitrogen metabolite repression mediated by the GATA factor AreA.
      These genes are strictly co-regulated by HxnR. Within the hxnR gene, constitutive
      mutations map in two discrete regions. Aspergillus nidulans is capable of using
      nicotinate and its oxidation products 6-hydroxynicotinic acid and 2,5
      dihydroxypyridine as sole nitrogen sources in an HxnR-dependent way. HxnS is
      highly similar to HxA, the canonical xanthine dehydrogenase (XDH), and has
      originated by gene duplication, preceding the origin of the Pezizomycotina. This
      cluster is conserved with some variations throughout the Aspergillaceae. Our
      results imply that a fungal pathway has arisen independently from bacterial ones.
      Significantly, the neo-functionalization of XDH into nicotinate hydroxylase has
      occurred independently from analogous events in bacteria. This work describes for
      the first time a gene cluster involved in nicotinate catabolism in a eukaryote
      and has relevance for the formation and evolution of co-regulated primary
      metabolic gene clusters and the microbial degradation of N-heterocyclic
      compounds.

PMID- 29212712
TI  - A reversible thermoresponsive sealant for temporary closure of ocular trauma.
AB  - Open globe injuries are full-thickness injuries sustained to the eye wall (cornea
      or sclera), which cause immediate drops in intraocular pressure that may lead to
      retinal detachment and permanent vision loss if not treated rapidly after injury.
      The current standard of care for open globe injuries consists of suturing the
      margins closed, but the technique can be time-consuming, requires specialized
      training and equipment, and can lead to patient discomfort, abrasion, and
      infection from eye rubbing. We engineered an injectable, thermoresponsive sealant
      (TRS) and a custom tool to occlude open globe injuries. The smart hydrogel
      sealant consists of physically cross-linked N-isopropylacrylamide copolymerized
      with butylacrylate. At low temperatures, it can be injected as a liquid, and when
      raised to body temperature, a heat-induced gelation converts the hydrogel into a
      solidified occlusion. The sealant can be repositioned or removed without causing
      additional trauma via exposure to cold water. In vitro and ex vivo assessments of
      mechanical adhesion to eye tissue revealed maintenance of intraocular pressure
      that is five times greater than the physiological range with reversible seal
      strength comparable to cyanoacrylate (super glue). In vivo assessment in a rabbit
      model of ocular trauma demonstrated ease of use for TRS deployment, statistically
      significant improvement in wound sealing, and no evidence of neurotoxicity,
      retinal tissue degradation, or significant chronic inflammatory response after 30
      days of exposure. Given the advantages of body heat-induced gelation, rapid
      reversible occlusion, and in vivo safety and efficacy, shape-adaptable TRSs have
      translational potential as smart wound sealants for temporary occlusion of
      surgical incisions or traumatic injuries.

PMID- 29212711
TI  - PPARdelta activation by bexarotene promotes neuroprotection by restoring
      bioenergetic and quality control homeostasis.
AB  - Neurons must maintain protein and mitochondrial quality control for optimal
      function, an energetically expensive process. The peroxisome proliferator
      activated receptors (PPARs) are ligand-activated transcription factors that
      promote mitochondrial biogenesis and oxidative metabolism. We recently determined
      that transcriptional dysregulation of PPARdelta contributes to Huntington's
      disease (HD), a progressive neurodegenerative disorder resulting from a CAG
      polyglutamine repeat expansion in the huntingtin gene. We documented that the
      PPARdelta agonist KD3010 is an effective therapy for HD in a mouse model.
      PPARdelta forms a heterodimer with the retinoid X receptor (RXR), and RXR
      agonists are capable of promoting PPARdelta activation. One compound with potent
      RXR agonist activity is the U.S. Food and Drug Administration-approved drug
      bexarotene. We tested the therapeutic potential of bexarotene in HD and found
      that bexarotene was neuroprotective in cellular models of HD, including medium
      spiny-like neurons generated from induced pluripotent stem cells (iPSCs) derived
      from patients with HD. To evaluate bexarotene as a treatment for HD, we treated
      the N171-82Q mouse model with the drug and found that bexarotene improved motor
      function, reduced neurodegeneration, and increased survival. To determine the
      basis for PPARdelta neuroprotection, we evaluated metabolic function and noted
      markedly impaired oxidative metabolism in HD neurons, which was rescued by
      bexarotene or KD3010. We examined mitochondrial and protein quality control in
      cellular models of HD and observed that treatment with a PPARdelta agonist
      promoted cellular quality control. By boosting cellular activities that are
      dysfunctional in HD, PPARdelta activation may have therapeutic applications in HD
      and potentially other neurodegenerative diseases.

PMID- 29212714
TI  - Erratum for the Research Article: "The FcRn inhibitor rozanolixizumab reduces
      human serum IgG concentration: A randomized phase 1 study" by P. Kiessling, R.
      Lledo-Garcia, S. Watanabe, G. Langdon, D. Tran, M. Bari, L. Christodoulou, E.
      Jones, G. Price, B. Smith, F. Brennan, I. White, S. Jolles.

PMID- 29212713
TI  - A degradation fragment of type X collagen is a real-time marker for bone growth
      velocity.
AB  - Despite its importance as a key parameter of child health and development, growth
      velocity is difficult to determine in real time because skeletal growth is slow
      and clinical tools to accurately detect very small increments of growth do not
      exist. We report discovery of a marker for skeletal growth in infants and
      children. The intact trimeric noncollagenous 1 (NC1) domain of type X collagen,
      the marker we designated as CXM for Collagen X Marker, is a degradation by
      product of endochondral ossification that is released into the circulation in
      proportion to overall growth plate activity. This marker corresponds to the rate
      of linear bone growth at time of measurement. Serum concentrations of CXM plotted
      against age show a pattern similar to well-established height growth velocity
      curves and correlate with height growth velocity calculated from incremental
      height measurements in this study. The CXM marker is stable once collected and
      can be accurately assayed in serum, plasma, and dried blood spots. CXM testing
      may be useful for monitoring growth in the pediatric population, especially
      responses of infants and children with genetic and acquired growth disorders to
      interventions that target the underlying growth disturbances. The utility of CXM
      may potentially extend to managing other conditions such as fracture healing,
      scoliosis, arthritis, or cancer.

PMID- 29212715
TI  - BCAS1 expression defines a population of early myelinating oligodendrocytes in
      multiple sclerosis lesions.
AB  - Investigations into brain function and disease depend on the precise
      classification of neural cell types. Cells of the oligodendrocyte lineage differ
      greatly in their morphology, but accurate identification has thus far only been
      possible for oligodendrocyte progenitor cells and mature oligodendrocytes in
      humans. We find that breast carcinoma amplified sequence 1 (BCAS1) expression
      identifies an oligodendroglial subpopulation in the mouse and human brain. These
      cells are newly formed, myelinating oligodendrocytes that segregate from
      oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of
      active myelin formation in development and in the adult. We find that BCAS1+
      oligodendrocytes are restricted to the fetal and early postnatal human white
      matter but remain in the cortical gray matter until old age. BCAS1+
      oligodendrocytes are reformed after experimental demyelination and found in a
      proportion of chronic white matter lesions of patients with multiple sclerosis
      (MS) even in a subset of patients with advanced disease. Our work identifies a
      means to map ongoing myelin formation in health and disease and presents a
      potential cellular target for remyelination therapies in MS.

PMID- 29212716
TI  - A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV
      infected individuals who initiated antiretroviral therapy early in infection.
AB  - Despite substantial clinical benefits, complete eradication of HIV has not been
      possible using antiretroviral therapy (ART) alone. Strategies that can either
      eliminate persistent viral reservoirs or boost host immunity to prevent rebound
      of virus from these reservoirs after discontinuation of ART are needed; one
      possibility is therapeutic vaccination. We report the results of a randomized,
      placebo-controlled trial of a therapeutic vaccine regimen in patients in whom ART
      was initiated during the early stage of HIV infection and whose immune system was
      anticipated to be relatively intact. The objectives of our study were to
      determine whether the vaccine was safe and could induce an immune response that
      would maintain suppression of plasma viremia after discontinuation of ART.
      Vaccinations were well tolerated with no serious adverse events but produced only
      modest augmentation of existing HIV-specific CD4+ T cell responses, with little
      augmentation of CD8+ T cell responses. Compared with placebo, the vaccination
      regimen had no significant effect on the kinetics or magnitude of viral rebound
      after interruption of ART and no impact on the size of the HIV reservoir in the
      CD4+ T cell compartment. Notably, 26% of subjects in the placebo arm exhibited
      sustained suppression of viremia (<400 copies/ml) after treatment interruption, a
      rate of spontaneous suppression higher than previously reported. Our findings
      regarding the degree and kinetics of plasma viral rebound after ART interruption
      have potentially important implications for the design of future trials testing
      interventions aimed at achieving ART-free control of HIV infection.

PMID- 29212717
TI  - Adaptation in response to environmental unpredictability.
AB  - Understanding how organisms adaptively respond to environmental fluctuations is a
      fundamental question in evolutionary biology. The Mediterranean region typically
      exhibits levels of environmental unpredictability that vary greatly in habitats
      over small geographical scales. In cyclically parthenogenetic rotifers, clonal
      proliferation occurs along with occasional bouts of sex. These bouts contribute
      to the production of diapausing eggs, which allows survival between growing
      seasons. Here, we studied two diapause-related traits in rotifers using clones
      from nine Brachionus plicatilis natural populations that vary in the degree of
      environmental unpredictability. We tested the hypothesis that the level of
      environmental unpredictability is directly related to the propensity for sex and
      inversely related to the hatching fraction of diapausing eggs. We found
      significant levels of genetic variation within populations for both traits.
      Interestingly, a positive correlation between pond unpredictability-quantified in
      a previous study from satellite imagery-and the propensity for sex was found.
      This correlation suggests a conservative, bet-hedging strategy that provides
      protection against unexpectedly short growing seasons. By contrast, the hatching
      fraction of diapausing eggs was not related to the level of environmental
      predictability. Our results highlight the ability of rotifer populations to
      locally adapt to time-varying environments, providing an evolutionarily relevant
      step forward in relating life-history traits to a quantitative measure of
      environmental unpredictability.

PMID- 29212718
TI  - The persistence of multiple strains of avian influenza in live bird markets.
AB  - Multiple subtypes of avian influenza (AI) and novel reassortants are frequently
      isolated from live bird markets (LBMs). However, our understanding of the drivers
      of persistence of multiple AI subtypes is limited. We propose a stochastic model
      of AI transmission within an LBM that incorporates market size, turnover rate and
      the balance of direct versus environmental transmissibility. We investigate the
      relationship between these factors and the critical community size (CCS) for the
      persistence of single and multiple AI strains within an LBM. We fit different
      models of seeding from farms to two-strain surveillance data collected from
      Shantou, China. For a single strain and plausible estimates for continuous
      turnover rates and transmissibility, the CCS was approximately 11 800 birds, only
      a 4.2% increase in this estimate was needed to ensure persistence of the co
      infecting strains (two strains in a single host). Precise values of CCS estimates
      were sensitive to changes in market turnover rate and duration of the latent
      period. Assuming a gradual daily sell rate of birds the estimated CCS was higher
      than when an instantaneous selling rate was assumed. We were able to reproduce
      prevalence dynamics similar to observations from a single market in China with
      infection seeded every 5-15 days, and a maximum non-seeding duration of 80 days.
      Our findings suggest that persistence of co-infections is more likely to be owing
      to sequential infection of single strains rather than ongoing transmission of
      both strains concurrently. In any given system for a fixed set of ecological and
      epidemiological conditions, there is an LBM size below which the risk of
      sustained co-circulation is low and which may suggest a clear policy opportunity
      to reduce the frequency of influenza co-infection in poultry.

PMID- 29212719
TI  - A novel pathway of nutrient absorption in crustaceans: branchial amino acid
      uptake in the green shore crab (Carcinus maenas).
AB  - Estuaries are environments enriched with dissolved nutrients such as amino acids.
      To date, marine arthropods are the only invertebrate group that have not been
      demonstrated to access this potentially important nutrient resource. Using in
      vitro gill perfusion techniques, we sought to investigate the ability of the
      green shore crab (Carcinus maenas) to take up the amino acid l-leucine directly
      from the water. Investigation of the concentration-dependent transport kinetics
      of radiolabelled l-leucine showed that there are two specific transport pathways
      across Carcinus gills, one with high affinity and low capacity, and the other
      with high capacity and low affinity. Using putative competitive substrates and
      reduced sodium preparations, we were able to identify the putative amino acid
      transport system associated with high-affinity uptake. This is the first study to
      demonstrate the absorption of dissolved organic nutrients across the gill
      epithelium of a marine arthropod.

PMID- 29212720
TI  - Co-occurrence of related asexual, but not sexual, lineages suggests that
      reproductive interference limits coexistence.
AB  - We used randomizations to analyse patterns of co-occurrence of sexual and
      apomictic (asexual) members of the North American Crepis agamic complex
      (Asteraceae). We expect strong asymmetry in reproductive interactions in Crepis:
      apomicts produce clonal seeds with no need for pollination and are not subject to
      reproductive interference from co-occurring relatives. However, because they
      still produce some viable pollen, apomicts can reduce reproductive success of
      nearby sexual relatives, potentially leading to eventual local exclusion of
      sexuals. Consistent with this, randomizations reveal that sexuals are over
      represented in isolated sites, while apomicts freely co-occur. Incorporation of
      taxonomic and phylogenetic evidence indicates that this pattern is not driven by
      local origins of asexuals. Our evidence that patterns of local co-occurrence are
      structured by reproductive interference suggests an underappreciated role for
      these interactions in community assembly, and highlights the need for explicit
      tests of the relative contributions of ecological and reproductive interactions
      in generating patterns of limiting similarity.

PMID- 29212721
TI  - Inter-annual variation in seed production has increased over time (1900-2014).
AB  - Mast seeding, or masting, is the highly variable and spatially synchronous
      production of seeds by a population of plants. The production of variable seed
      crops is typically correlated with weather, so it is of considerable interest
      whether global climate change has altered the variability of masting or the size
      of masting events. We compiled 1086 datasets of plant seed production spanning
      1900-2014 and from around the world, and then analysed whether the coefficient of
      variation (CV) in seed set, a measure of masting, increased over time. Over this
      115-year period, seed set became more variable for plants as a whole and for the
      particularly well-studied taxa of conifers and oaks. The increase in CV
      corresponded with a decrease in the long-term mean of seed set of plant species.
      Seed set CV increased to a greater degree in plant taxa with a tendency towards
      masting. Seed set is becoming more variable among years, especially for plant
      taxa whose masting events are known to affect animal populations. Such subtle
      change in reproduction can have wide-ranging effects on ecosystems because seed
      crops provide critical resources for a wide range of taxa and have cascading
      effects throughout food webs.

PMID- 29212722
TI  - First satellite tracks of South Atlantic sea turtle 'lost years': seasonal
      variation in trans-equatorial movement.
AB  - In the South Atlantic Ocean, few data exist regarding the dispersal of young
      oceanic sea turtles. We characterized the movements of laboratory-reared yearling
      loggerhead turtles from Brazilian rookeries using novel telemetry techniques,
      testing for differences in dispersal during different periods of the sea turtle
      hatching season that correspond to seasonal changes in ocean currents.
      Oceanographic drifters deployed alongside satellite-tagged turtles allowed us to
      explore the mechanisms of dispersal (passive drift or active swimming). Early in
      the hatching season turtles transited south with strong southward currents. Late
      in the hatching season, when currents flowed in the opposite direction, turtles
      uniformly moved northwards across the Equator. However, the movement of
      individuals differed from what was predicted by surface currents alone. Swimming
      velocity inferred from track data and an ocean circulation model strongly suggest
      that turtles' swimming plays a role in maintaining their position within frontal
      zones seaward of the continental shelf. The long nesting season of adults and
      behaviour of post-hatchlings exposes young turtles to seasonally varying ocean
      conditions that lead some individuals further into the South Atlantic and others
      into the Northern Hemisphere. Such migratory route diversity may ultimately
      buffer the population against environmental changes or anthropologic threats,
      fostering population resiliency.

PMID- 29212723
TI  - Intraspecific and interspecific variation in thermotolerance and photoacclimation
      in Symbiodinium dinoflagellates.
AB  - Light and temperature are major drivers in the ecology and biogeography of
      symbiotic dinoflagellates living in corals and other cnidarians. We examined
      variations in physiology among 11 strains comprising five species of clade A
      Symbiodinium We grew cultures at 26 degrees C (control) and 32 degrees C (high
      temperature) over a duration of 18 days while measuring growth and photochemical
      efficiency (Fv /Fm ). Responses to thermal stress ranged from susceptible to
      tolerant across species and strains. Most strains exhibited a decrease in cell
      densities and Fv /Fm when grown at 32 degrees C. Tolerance to high temperature
      (T32) was calculated for all strains, ranging from 0 (unable to survive at high
      temperature) to 1 (able survive at high temperature). There was substantial
      variation in thermotolerance across species and among strains. One strain had a
      T32 close to 1, indicating that growth was not reduced at 32 degrees C for only
      this one strain. To evaluate the combined effect of temperature and light on
      physiological stress, we selected three strains with different levels of
      thermotolerance (tolerant, intermediate and susceptible) and grew them under five
      different light intensities (65, 80, 100, 240 and 443 umol quanta m-2 s-1) at 26
      and 32 degrees C. High irradiance exacerbated the effect of high temperature,
      particularly in strains from thermally sensitive species. This work further
      supports the recognition that broad physiological differences exist not only
      among species within Symbiodinium clades, but also among strains within species
      demonstrating that thermotolerance varies widely between species and among
      strains within species.

PMID- 29212724
TI  - Major histocompatibility complex-linked social signalling affects female
      fertility.
AB  - Genes of the major histocompatibility complex (MHC) have been shown to influence
      social signalling and mate preferences in many species, including humans. First
      observations suggest that MHC signalling may also affect female fertility. To
      test this hypothesis, we exposed 191 female horses (Equus caballus) to either an
      MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and
      conception. A within-subject experimental design controlled for non-MHC-linked
      male characteristics, and instrumental insemination with semen of other males (n
      = 106) controlled for potential confounding effects of semen or embryo
      characteristics. We found that females were more likely to become pregnant if
      exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic
      distance to the stimulus males (based on microsatellite markers on 20
      chromosomes) had no effect. Our results demonstrate that early pregnancy failures
      can be due to maternal life-history decisions (cryptic female choice) influenced
      by MHC-linked social signalling.

PMID- 29212725
TI  - The functional syndrome: linking individual trait variability to ecosystem
      functioning.
AB  - Phenotypic variability is increasingly assessed through functional response and
      effect traits, which provide a mechanistic framework for investigating how an
      organism responds to varying ecological factors and how these responses affect
      ecosystem functioning. Covariation between response and effect traits has been
      poorly examined at the intraspecific level, thus hampering progress in
      understanding how phenotypic variability alters the role of organisms in
      ecosystems. Using a multi-trait approach and a nine-month longitudinal monitoring
      of individual red-swamp crayfish (Procambarus clarkii), we demonstrated that most
      of the measured response and effect traits were partially stable during the
      ontogeny of individuals. Suites of response and effect traits were associated
      with a response syndrome and an effect syndrome, respectively, which were
      correlated to form a functional syndrome. Using a bioenergetic model, we
      predicted that differences in the response syndrome composition of hypothetical
      populations had important ecological effects on a key ecosystem process (i.e.
      whole-lake litter decomposition) to a level similar to those induced by doubling
      population size. Demonstrating the existence of a functional syndrome is likely
      to improve our understanding of the ecological impacts of phenotypic variation
      among individuals in wild populations across levels of biological organization,
      and the linkage between ecosystem and evolutionary ecology.

PMID- 29212726
TI  - Rapid evolution rescues hosts from competition and disease but-despite a dilution
      effect-increases the density of infected hosts.
AB  - Virulent parasites can depress the densities of their hosts. Taxa that reduce
      disease via dilution effects might alleviate this burden. However, 'diluter' taxa
      can also depress host densities through competition for shared resources. The
      combination of disease and interspecific competition could even drive hosts
      extinct. Then again, genetically variable host populations can evolve in response
      to both competitors and parasites. Can rapid evolution rescue host density from
      the harm caused by these ecological enemies? How might such evolution influence
      dilution effects or the size of epidemics? In a mesocosm experiment with
      planktonic hosts, we illustrate the joint harm of competition and disease: hosts
      with constrained evolutionary ability (limited phenotypic variation) suffered
      greatly from both. However, populations starting with broader phenotypic
      variation evolved stronger competitive ability during epidemics. In turn,
      enhanced competitive ability-driven especially by parasites-rescued host
      densities from the negative impacts of competition, disease, and especially their
      combination. Interspecific competitors reduced disease (supporting dilution
      effects) even when hosts rapidly evolved. However, this evolutionary response
      also elicited a potential problem. Populations that evolved enhanced competitive
      ability and maintained robust total densities also supported higher densities of
      infections. Thus, rapid evolution rescued host densities but also unleashed
      larger epidemics.

PMID- 29212727
TI  - Deep pelagic food web structure as revealed by in situ feeding observations.
AB  - Food web linkages, or the feeding relationships between species inhabiting a
      shared ecosystem, are an ecological lens through which ecosystem structure and
      function can be assessed, and thus are fundamental to informing sustainable
      resource management. Empirical feeding datasets have traditionally been
      painstakingly generated from stomach content analysis, direct observations and
      from biochemical trophic markers (stable isotopes, fatty acids, molecular tools).
      Each approach carries inherent biases and limitations, as well as advantages.
      Here, using 27 years (1991-2016) of in situ feeding observations collected by
      remotely operated vehicles (ROVs), we quantitatively characterize the deep
      pelagic food web of central California within the California Current,
      complementing existing studies of diet and trophic interactions with a unique
      perspective. Seven hundred and forty-three independent feeding events were
      observed with ROVs from near-surface waters down to depths approaching 4000 m,
      involving an assemblage of 84 different predators and 82 different prey types,
      for a total of 242 unique feeding relationships. The greatest diversity of prey
      was consumed by narcomedusae, followed by physonect siphonophores, ctenophores
      and cephalopods. We highlight key interactions within the poorly understood
      'jelly web', showing the importance of medusae, ctenophores and siphonophores as
      key predators, whose ecological significance is comparable to large fish and
      squid species within the central California deep pelagic food web. Gelatinous
      predators are often thought to comprise relatively inefficient trophic pathways
      within marine communities, but we build upon previous findings to document their
      substantial and integral roles in deep pelagic food webs.

PMID- 29212728
TI  - Coral calcification mechanisms facilitate adaptive responses to ocean
      acidification.
AB  - Ocean acidification (OA) is a pressing threat to reef-building corals, but it
      remains poorly understood how coral calcification is inhibited by OA and whether
      corals could acclimatize and/or adapt to OA. Using a novel geochemical approach,
      we reconstructed the carbonate chemistry of the calcifying fluid in two coral
      species using both a pH and dissolved inorganic carbon (DIC) proxy (delta11B and
      B/Ca, respectively). To address the potential for adaptive responses, both
      species were collected from two sites spanning a natural gradient in seawater pH
      and temperature, and then subjected to three pHT levels (8.04, 7.88, 7.71)
      crossed by two temperatures (control, +1.5 degrees C) for 14 weeks. Corals from
      the site with naturally lower seawater pH calcified faster and maintained growth
      better under simulated OA than corals from the higher-pH site. This ability was
      consistently linked to higher pH yet lower DIC values in the calcifying fluid,
      suggesting that these differences are the result of long-term acclimatization
      and/or local adaptation to naturally lower seawater pH. Nevertheless, all corals
      elevated both pH and DIC significantly over seawater values, even under OA. This
      implies that high pH upregulation combined with moderate levels of DIC
      upregulation promote resistance and adaptive responses of coral calcification to
      OA.

PMID- 29212729
TI  - Condition-dependent female preference for male genitalia length is based on male
      reproductive tactics.
AB  - There is extensive morphological variation of male genitalia across animals with
      internal fertilization, even among closely related species. Most studies
      attempting to explain this extraordinary diversity have focused on processes that
      occur post-copula (e.g. sperm competition, cryptic female choice). Only a few
      studies have focused on the pre-copula process of female preference. In addition,
      the extent to which this variation could be associated with the use of different
      reproductive tactics has yet to be explored. Here, we show that female preference
      for male genitalia length in two livebearing fishes depends on the type of
      reproductive tactic of the males being evaluated as well as the body condition of
      the female. In a species where all males coax females to acquire matings
      (courters), females preferred males with short genitalia. In a species with
      genetically influenced alternative reproductive tactics (courter males that only
      court and produce courter sons, sneaker males that use the coercive tactic of
      sneak chase and produce sneaker sons), female preference depended on an
      interaction between male tactic and female condition: females in good condition
      preferred courter males with short genitalia, and sneaker males with long
      genitalia. Our results suggest that female preference for male traits favourable
      to their sons may be an important factor contributing to the diversification of
      male genitalia. Despite the contrasting selection for genitalia length that our
      female preference tests suggest, we found no significant differences in genitalia
      length between coaxing (courters) and coercive (sneakers) males. Our study
      represents a starting point to more clearly understand the role of alternative
      reproductive tactics and variation in female mate preference in the evolution of
      male genitalia.

PMID- 29212730
TI  - Hierarchical social networks shape gut microbial composition in wild Verreaux's
      sifaka.
AB  - In wild primates, social behaviour influences exposure to environmentally
      acquired and directly transmitted microorganisms. Prior studies indicate that gut
      microbiota reflect pairwise social interactions among chimpanzee and baboon
      hosts. Here, we demonstrate that higher-order social network structure-beyond
      just pairwise interactions-drives gut bacterial composition in wild lemurs, which
      live in smaller and more cohesive groups than previously studied anthropoid
      species. Using 16S rRNA gene sequencing and social network analysis of grooming
      contacts, we estimate the relative impacts of hierarchical (i.e. multilevel)
      social structure, individual demographic traits, diet, scent-marking, and habitat
      overlap on bacteria acquisition in a wild population of Verreaux's sifaka
      (Propithecus verreauxi) consisting of seven social groups. We show that social
      group membership is clearly reflected in the microbiomes of individual sifaka,
      and that social groups with denser grooming networks have more homogeneous gut
      microbial compositions. Within social groups, adults, more gregarious
      individuals, and individuals that scent-mark frequently harbour the greatest
      microbial diversity. Thus, the community structure of wild lemurs governs
      symbiotic relationships by constraining transmission between hosts and
      partitioning environmental exposure to microorganisms. This social cultivation of
      mutualistic gut flora may be an evolutionary benefit of tight-knit group living.

PMID- 29212731
TI  - Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round
      Cell Tumor.
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an aggressive, often
      fatal soft tissue sarcoma that lacks an optimal salvage regimen. We
      retrospectively reviewed data from 29 pretreated DSRCT patients who received
      pazopanib at MD Anderson Cancer Center after failure of standard chemotherapies.
      SUBJECTS, MATERIALS, AND METHODS: Medical records of patients treated from
      January 2012 to December 2016 were reviewed and regression analyses were
      performed. Median progression-free survival (PFS) and overall survival (OS) were
      estimated using the Kaplan-Meier method and differences in survival were assessed
      by a log-rank test. A landmark statistical analysis was used to assess OS at a
      predefined 12-week time point following pazopanib initiation. RESULTS: The mean
      age at pazopanib treatment was 27.5 years (range, 6.3-50.1 years). According to
      RECIST 1.1 criteria, 16 patients (55%) had stable disease, 1 patient (3%) had
      partial response, 1 patient (3%) had complete response, and 11 patients (38%) had
      progressive disease. Estimated median PFS was 5.63 months (95% confidence
      interval [CI]: 3.23-7.47). Median OS was 15.7 months (95% CI: 10.3-32.4). As of
      December 2016, 11 patients (38%) were still alive, with a median follow-up time
      of 16.8 (range 3.8-30.1) months. Doses between 400 and 800 mg were included.
      Pazopanib was well tolerated and 23 (79%) of the patients continued it until
      progression or death, 4 discontinued because of side effects, and 2 were still on
      pazopanib at the time of data analysis. CONCLUSION: In the largest study
      conducted to date in DSRCT, pazopanib was well tolerated and clinically active in
      heavily pretreated patients who otherwise lack good treatment options.
      IMPLICATIONS FOR PRACTICE: Desmoplastic small round cell tumor (DSRCT) is a rare,
      extremely aggressive soft tissue sarcoma subtype that most commonly occurs in
      adolescent and young adult males. No DSRCT-specific therapies exist, and for lack
      of a better treatment approach, current therapies have relied upon U.S. Food and
      Drug Administration-approved drugs like pazopanib that exhibit clinical activity
      in other sarcoma subtypes. This article describes the largest experience to date
      using pazopanib as salvage treatment in heavily pretreated DSRCT patients.
      Pazopanib was well tolerated and clinically active, surpassing predefined metrics
      proposed by the European Organization for Research and Treatment of Cancer
      indicative of "active" sarcoma drugs (5.63 months progression-free survival
      [PSF], with 62% of the study population achieving progression-free survival at 12
      weeks).

PMID- 29212732
TI  - The Role of Rituximab in Chronic Lymphocytic Leukemia Treatment and the Potential
      Utility of Biosimilars.
AB  - : Chronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic
      or clinically silent disease; pharmacologic intervention is generally required
      for symptomatic patients with clinically significant adenopathy or cytopenia. In
      the front-line treatment of CLL, the current standard-of-care includes
      chemotherapy in combination with an anti-CD20 monoclonal antibody (e.g.,
      rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the
      evolving treatment paradigm toward targeted therapy, it is likely that rituximab
      (plus chemotherapy), with or without targeted agents, will retain a significant
      role in CLL treatment. However, patents for many biologics, including rituximab,
      have expired or will expire in the near future. Furthermore, access to rituximab
      has remained challenging, particularly in countries with restricted resources.
      Together, these concerns have prompted the development of safe and effective
      rituximab biosimilars. The term "biosimilar" refers to a biologic that is highly
      similar to an approved reference (originator) product, notwithstanding minor
      differences in clinically inactive components, and for which there are no
      clinically meaningful differences in purity, potency, or safety. Biosimilars are
      developed to treat the same condition(s) using the same treatment regimens as an
      approved reference biologic and have the potential to increase access to more
      affordable treatments. We review the importance of rituximab in the current
      treatment of CLL, the scientific basis of its future role in combination with
      chemotherapy, and the role of new and emerging agents in the treatment of CLL,
      which could potentially be used in combination with rituximab biosimilars. We
      also discuss rituximab biosimilars currently in development. IMPLICATIONS FOR
      PRACTICE: Front-line treatments for chronic lymphocytic leukemia (CLL) include
      chemotherapy in combination with an anti-CD20 monoclonal antibody (e.g.,
      rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the
      evolving treatment paradigm, it is likely rituximab (plus chemotherapy) and
      targeted agents undergoing clinical evaluation will retain a significant role in
      CLL treatment. However, patents for many biologics, including rituximab, have
      expired or will expire in the near future and, in many regions, access to
      rituximab remains challenging. Together, these concerns have prompted the
      development of safe and effective rituximab biosimilars, with the potential to
      increase access to more affordable treatments.

PMID- 29212733
TI  - Successful Ovarian Stimulation for Fertility Preservation in a Patient with
      Chronic Myeloid Leukemia: Switch from Nilotinib to Interferon-alpha.
AB  - The development of tyrosine-kinase inhibitors (TKIs) has improved survival of
      patients with chronic myeloid leukemia (CML). Some patients may become resistant
      to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly
      gonadotoxic. Fertility preservation with ovarian stimulation might be indicated
      but is challenging if patients need to remain on TKIs until HSCT because TKIs may
      compromise follicular development and response to ovarian stimulation. We report
      the case of a patient with CML resistant to TKI and planned for an HSCT, in which
      treatment by TKI was replaced by interferon-alpha before and during ovarian
      stimulation for fertility preservation. Successful ovarian stimulation was
      performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell
      transplantation was performed, and at present, 3 years later, the patient
      presents a sustained major molecular response.

PMID- 29212734
TI  - Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the
      Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy.
AB  - LESSONS LEARNED: There is no presenting parameter that predicts the success of
      neoadjuvant therapy for pancreatic cancer.Despite the images on scans following
      neoadjuvant therapy, all patients should be evaluated, because inflammation
      following radiation therapy (RT) may overstate the extent of tumor and vascular
      involvement. BACKGROUND: In patients presenting with locally advanced pancreatic
      adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed
      presenting tumor size, extent of vascular involvement, tumor markers, response to
      neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without
      additional chemoradiotherapy with GX on R0 resection rates (>=2 mm margins), and
      survival. METHODS: All patients had baseline magnetic resonance imaging (MRI)
      and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline
      positron emission tomography-computed tomography (PET-CT) was performed in 39
      patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2
      and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1-14)
      was administered on a 3-week schedule for 6 cycles to patients with both arterial
      and venous-only involvement. Patients in the arterial arm received GX/RT before
      surgery, and those in the venous arm received GX/RT after R1 resection. Standard
      dose RT was delivered by intensity-modulated radiation therapy (IMRT) or
      conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine
      on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A
      cancer antigen test 19-9 (CA 19-9) was obtained at baseline and days 4 and 11 of
      each cycle. The rate of change in CA 19-9 was calculated using the formula:
      (Log10 CA 19-9 time 0) - (Log10 CA 19-9 at 9 weeks)/9 weeks. This was derived
      based on the observation that the fall in CA 19-9 following effective
      chemotherapy is a second-order function. RESULTS: Of the 34 patients with
      arterial involvement and 11 with extensive venous involvement who met the
      eligibility criteria and began GTX, only 5 patients in the arterial arm did not
      undergo subsequent resection. The remaining 40 patients were included in this
      analysis of presenting parameters with respect to R0 resection, disease-free
      survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40
      patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0
      resection was a median 37 months (95% confidence interval [CI]: 29.3-44.7)
      compared with 29 months (95% CI: 28.5-41.5) for those with R1 resection.Excluding
      four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31
      months (95% CI: 11.3-51.1), and the median DFS for R1 resection was only 14
      months (95% CI: 11.1-17). Eleven of the twenty-eight (39%) patients achieving R0
      resection have not relapsed (median = 45 months, range = 25-71 months).
      CONCLUSION: R0 resection, the goal of neoadjuvant treatment, can be achieved in
      70% of patients presenting with locally advanced pancreatic cancer. The median
      DFS was 31 months (95% CI: 11. 3-51.1). No relationship was found with tumor
      size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19
      9, degree of tumor regression on scan, fall in CA 19-9, or SUV on PET scan and
      subsequent survival.

PMID- 29212735
TI  - Decision-Making Capacity for Chemotherapy and Associated Factors in Newly
      Diagnosed Patients with Lung Cancer.
AB  - BACKGROUND: The objective of this study was to assess decision-making capacity in
      patients newly diagnosed with lung cancer, clinical factors associated with
      impaired capacity, and physicians' perceptions of patients' decision-making
      capacity. MATERIALS AND METHODS: We recruited 122 patients newly diagnosed with
      lung cancer. One hundred fourteen completed the assessment. All patients were
      receiving a combination of treatments (e.g., chemotherapy, chemo-radiotherapy, or
      targeted therapy). Decision-making capacity was assessed using the MacArthur
      Competence Tool for Treatment. Cognitive impairment, depressive symptoms, and
      frailty were also evaluated. Physicians' perceptions were compared with the
      ascertainments. RESULTS: Twenty-seven (24%, 95% confidence interval [CI], 16-31)
      patients were judged to have incapacity. Clinical teams had difficulty in judging
      six (22.2%) patients for incapacity. Logistic regression identified frailty (odds
      ratio, 3.51; 95% CI, 1.13-10.8) and cognitive impairment (odds ratio, 5.45; 95%
      CI, 1.26-23.6) as the factors associated with decision-making incapacity. Brain
      metastasis, emphysema, and depression were not associated with decision-making
      incapacity. CONCLUSION: A substantial proportion of patients diagnosed with lung
      cancer show impairments in their capacity to make a medical decision. Assessment
      of cognitive impairment and frailty may provide appropriate decision-making
      frameworks to act in the best interest of patients. IMPLICATIONS FOR PRACTICE:
      Decision-making capacity is the cornerstone of clinical practice. A substantial
      proportion of patients with cancer show impairments in their capacity to make a
      medical decision. Assessment of cognitive impairment and frailty may provide
      appropriate decision-making frameworks to act in the best interest of patients.

PMID- 29212736
TI  - Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and
      Racial Differences in Stroke Study.
AB  - BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine
      urinary arsenic levels in relation to incident ischemic stroke in the United
      States. METHODS: We performed a case-cohort study nested within the REGARDS
      (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort
      (n=2486) of controls was randomly sampled within region-race-sex strata while all
      incident ischemic stroke cases from the full REGARDS cohort (n=671) were
      included. Baseline urinary arsenic was measured by inductively coupled plasma
      mass spectrometry. Arsenic species, including urinary inorganic arsenic and its
      metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a
      random subset (n=199). Weighted Cox's proportional hazards models were used to
      calculate hazard ratios and 95% confidence intervals of ischemic stroke by
      arsenic and its species. RESULTS: The average follow-up was 6.7 years. Although
      incident ischemic stroke showed no association with total arsenic or total
      inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid
      on a log-scale, after adjustment for potential confounders, ischemic stroke risk
      increased ~2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect
      modification by age, race, sex, or geographic region was not evident.
      CONCLUSIONS: A metabolite of arsenic was positively associated with incident
      ischemic stroke in this case-cohort study of the US general population, a low-to
      moderate exposure area. Overall, these findings suggest a potential role for
      arsenic methylation in the pathogenesis of stroke, having important implications
      for future cerebrovascular research.

PMID- 29212738
TI  - Stroke Incidence by Major Pathological Type and Ischemic Subtypes in the Auckland
      Regional Community Stroke Studies: Changes Between 2002 and 2011.
AB  - BACKGROUND AND PURPOSE: Major pathological stroke types (ischemic stroke [IS],
      primary intracerebral hemorrhage [ICH], and subarachnoid hemorrhage) and IS
      subtypes, have differing risk factors, management, and prognosis. We report
      changes in major stroke types and IS subtypes incidence during 10 years using
      data from the ARCOS (Auckland Regional Community Stroke Study) III performed
      during 12 months in 2002 to 2003 and the fourth ARCOS study (ARCOS-IV) performed
      in 2011 to 2012. METHODS: ARCOS-III and ARCOS-IV were population-based registers
      of all new strokes in the greater Auckland region (population aged >15 years, 1
      119 192). Strokes were classified into major pathological types (IS, ICH,
      subarachnoid hemorrhage, and undetermined type). Crude annual age-, sex-, and
      ethnic-specific stroke incidence with 95% confidence intervals was calculated.
      ISs were subclassified using TOAST (Trial of ORG 10172 in Acute Stroke Treatment)
      criteria into 5 etiologic groups. Rate ratios with 95% confidence intervals were
      calculated for differences in age-standardized rates between the 2 studies.
      RESULTS: In ARCOS-IV, there were 1329 (81%) ISs, 211 (13%) ICHs, 79 (5%)
      subarachnoid hemorrhages, and 24 (1%) undetermined type strokes. The proportional
      distribution of IS subtypes was 29% cardioembolism, 21% small-vessel occlusion,
      15% large-artery atherosclerosis, 5% other determined etiology, and 31%
      undetermined type. Between 2002 and 2011, age-standardized incidence decreased
      for subarachnoid hemorrhage (rate ratios, 0.73; 95% confidence intervals, 0.54
      0.99) and undetermined type (rate ratios, 0.14; 95% confidence intervals, 0.09
      0.22). Rates were stable for IS and ICH. Among IS subtypes, large-artery
      atherosclerosis and small-vessel occlusion rates increased significantly. The
      frequency of all risk factors increased in IS. Ethnic differences were observed
      for both stroke subtype rates and their risk factor frequencies. CONCLUSIONS: A
      lack of change in IS and ICH incidence may reflect a trend toward increased
      incidence of younger strokes. Increased rates of large-artery atherosclerosis and
      small-vessel occlusion are associated with increased smoking and high blood
      pressure. Ethnic differences in the proportional distribution of pathological
      stroke subtypes suggest differential exposure and susceptibility to risk factors.

PMID- 29212737
TI  - Astrocytic Lrp4 (Low-Density Lipoprotein Receptor-Related Protein 4) Contributes
      to Ischemia-Induced Brain Injury by Regulating ATP Release and Adenosine-A2AR
      (Adenosine A2A Receptor) Signaling.
AB  - BACKGROUND AND PURPOSE: Lrp4 (low-density lipoprotein receptor-related protein 4)
      is predominantly expressed in astrocytes, where it regulates glutamatergic
      neurotransmission by suppressing ATP release. Here, we investigated Lrp4's
      function in ischemia/stroke-induced brain injury response, which includes
      glutamate-induced neuronal death and reactive astrogliosis. METHODS: The brain
      specific Lrp4 conditional knockout mice (Lrp4GFAP-Cre), astrocytic-specific Lrp4
      conditional knockout mice (Lrp4GFAP-creER), and their control mice (Lrp4f/f) were
      subjected to photothrombotic ischemia and the transient middle cerebral artery
      occlusion. After ischemia/stroke, mice or their brain samples were subjected to
      behavior tests, brain histology, immunofluorescence staining, Western blot, and
      quantitative real-time polymerase chain reaction. In addition, primary astrocytes
      and neurons were cocultured with or without oxygen and glucose deprivation and in
      the presence or absence of the antagonist for adenosine-A2AR (adenosine A2A
      receptor) or ATP-P2X7R (P2X purinoceptor 7) signaling. Gliotransmitters, such as
      glutamate, d-serine, ATP, and adenosine, in the condition medium of cultured
      astrocytes were also measured. RESULTS: Lrp4, largely expressed in astrocytes,
      was increased in response to ischemia/stroke. Both Lrp4GFAP-Cre and Lrp4GFAP
      creER mice showed less brain injury, including reduced neuronal death, and
      impaired reactive astrogliosis. Mechanistically, Lrp4 conditional knockout in
      astrocytes increased ATP release and the production of ATP derivative, adenosine,
      which were further elevated by oxygen and glucose deprivation. Pharmacological
      inhibition of ATP-P2X7R or adenosine-A2AR signaling diminished Lrp4GFAP-creER's
      protective effect. CONCLUSIONS: The astrocytic Lrp4 plays an important role in
      ischemic brain injury response. Lrp4 deficiency in astrocytes seems to be
      protective in response to ischemic brain injury, likely because of the increased
      ATP release and adenosine-A2AR signaling.

PMID- 29212739
TI  - Response by Michel and Eskioglou to Letter Regarding Article, "Ischemic Amnesia:
      Causes and Outcome".

PMID- 29212741
TI  - Letter by Mugikura and Takahashi Regarding Article, "Ischemic Amnesia: Causes and
      Outcome".

PMID- 29212740
TI  - IL-23 (Interleukin-23)-Producing Conventional Dendritic Cells Control the
      Detrimental IL-17 (Interleukin-17) Response in Stroke.
AB  - BACKGROUND AND PURPOSE: Inflammatory mechanisms can exacerbate ischemic tissue
      damage and worsen clinical outcome in patients with stroke. Both alphabeta and
      gammadelta T cells are established mediators of tissue damage in stroke, and the
      role of dendritic cells (DCs) in inducing the early events of T cell activation
      and differentiation in stroke is not well understood. METHODS: In a murine model
      of experimental stroke, we defined the immune phenotype of infiltrating DC
      subsets based on flow cytometry of surface markers, the expression of ontogenetic
      markers, and cytokine levels. We used conditional DC depletion, bone marrow
      chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further
      explore the functional role of DCs. RESULTS: We show that the ischemic brain was
      rapidly infiltrated by IRF4+/CD172a+ conventional type 2 DCs and that
      conventional type 2 DCs were the most abundant subset in comparison with all
      other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs
      became the major source of IL-23, promoting neutrophil infiltration by induction
      of IL-17 (interleukin-17) in gammadelta T cells. Functionally, the depletion of
      CD11c+ cells or the genetic disruption of the IL-23 signaling abrogated both IL
      17 production in gammadelta T cells and neutrophil infiltration. Interruption of
      the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome
      after stroke. CONCLUSIONS: Our results suggest a central role for interferon
      regulatory factor 4-positive IL-23-producing conventional DCs in the IL-17
      dependent secondary tissue damage in stroke.

PMID- 29212742
TI  - Getting the First Grant.

PMID- 29212743
TI  - Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical
      Thrombectomy in Large-Vessel Occlusions.
AB  - BACKGROUND AND PURPOSE: Although current guidelines advocate pretreatment with
      intravenous thrombolysis (IVT) in all eligible patients with acute ischemic
      stroke with large-vessel occlusion before mechanical thrombectomy, there are
      observational data questioning the efficacy of this approach. One of the main
      arguments in favor of IVT pretreatment is the potential for tissue-type
      plasminogen activator-induced successful reperfusion (SR) before the onset of
      endovascular procedure. METHODS: We performed a systematic review and meta
      analysis of randomized controlled clinical trials and observational cohorts
      providing rates of SR with IVT in patients with large-vessel occlusion before the
      initiation of mechanical thrombectomy. We also performed subgroup analyses
      according to study type (randomized controlled clinical trials versus
      observational) and according to the inclusion per protocol of patients with
      tandem (intracranial/extracranial) occlusions. RESULTS: We identified 13 eligible
      studies (7 randomized controlled clinical trials and 6 observational cohorts),
      including 1561 patients with acute ischemic stroke (median National Institutes of
      Health Stroke Scale score, 17) with large-vessel occlusion. SR following IVT and
      before mechanical thrombectomy was documented in 11% (95% confidence interval, 7%
      16%), with no difference among cohorts derived from randomized controlled
      clinical trials and observational studies. There was significant heterogeneity
      across included studies both in the overall analysis and among subgroups (I2>84%;
      P for Cochran Q, <0.001). Higher tissue-type plasminogen activator-induced SR
      rates were documented in studies reporting the exclusion of tandem occlusions
      (17%; 95% confidence interval, 11%-23%) compared with the rest (7%; 95%
      confidence interval, 4%-11%; P for subgroup differences, 0.003). CONCLUSIONS:
      Pretreatment with systemic thrombolysis in patients with large-vessel occlusion
      eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the
      need for additional endovascular reperfusion. Tandem occlusions seem to be the
      least responsive to IVT pretreatment.

PMID- 29212744
TI  - Selective NLRP3 (Pyrin Domain-Containing Protein 3) Inflammasome Inhibitor
      Reduces Brain Injury After Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease
      without effective treatment. As a key component of the innate immune system, the
      NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3)
      inflammasome, when activated after ICH, promotes neuroinflammation and brain
      edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks
      NLRP3 activation at nanomolar concentrations. Here, we examined the effect of
      MCC950 on brain injury and inflammation in 2 models of ICH in mice. METHODS: In
      mice with ICH induced by injection of autologous blood or bacterial collagenase,
      we determined the therapeutic potential of MCC950 and its mechanisms of
      neuroprotection. RESULTS: MCC950 reduced IL-1beta (interleukin-1beta) production
      and attenuated neurodeficits and perihematomal brain edema after ICH induction by
      injection of either autologous blood or collagenase. In mice with autologous
      blood-induced ICH, the protection of MCC950 was associated with reduced leukocyte
      infiltration into the brain and microglial production of IL-6. MCC950 improved
      blood-brain barrier integrity and diminished cell death. Notably, the protective
      effect of MCC950 was abolished in mice depleted of either microglia or Gr-1+
      myeloid cells. CONCLUSIONS: These results indicate that the NLRP3 inflammasome
      inhibitor, MCC950, attenuates brain injury and inflammation after ICH. Hence,
      NLRP3 inflammasome inhibition is a potential therapy for ICH that warrants
      further investigation.

PMID- 29212745
TI  - Factors Associated With Focal Computed Tomographic Perfusion Abnormalities in
      Supratentorial Transient Ischemic Attacks.
AB  - BACKGROUND AND PURPOSE: Computed tomographic perfusion (CTP) is useful in
      diagnosis of patients with transient focal neurological symptoms. In acute
      imaging of patients with a suspected transient ischemic attack (TIA), it remains
      unclear which patients develop focal perfusion abnormalities (FPA), that is,
      hypoperfusion or hyperperfusion. We aimed at determining independent factors
      associated with FPA in patients with supratentorial TIAs. METHODS: We
      prospectively collected consecutive patients with supratentorial TIAs defined by
      the traditional time-based definition who underwent CTP within 24 hours of
      symptom onset. We recorded demographics, risk factors, clinical features,
      severity, and timing from onset. We documented the Age, Blood Pressure, Clinical
      Features, Duration, and Diabetes (ABCD2) scores, vascular territories, and
      presence of relevant arterial pathology. Variables were tested for an association
      with FPA with univariate and multivariate analyses. RESULTS: A hundred and ten of
      265 patients (42%) with supratentorial TIAs had FPA on CTP. Acute noncontrast
      computed tomography showed early ischemic lesions in 6%, and acute/subacute
      magnetic resonance imaging was pathological in 52 of the 109 cases (47.7%) where
      it was performed. Clinical factors associated with FPA were high-admission
      National Institutes of Health Stroke Scale (odds ratio [OR], 1.22), right
      hemispheric TIA (OR, 3.09), and cardioembolic mechanism (OR, 2.19). Persistence
      of symptoms during CTP (OR, 2.59), shorter duration of TIA (OR, 0.93), major
      intracranial arterial pathology (OR, 12.5), and extracranial arterial occlusion
      (OR, 7.44) were also associated with FPA. CONCLUSIONS: Supratentorial TIAs are
      often associated with FPA in CTP, even after symptom resolution. FPAs are
      frequent in severe TIAs and those associated with cardioembolism or specific
      arterial pathologies. These findings can help clinicians in accurate diagnosis of
      TIA and its underlying mechanisms.

PMID- 29212746
TI  - New Data Support Patent Foramen Ovale Closure After Stroke.

PMID- 29212747
TI  - Primary Thrombectomy in tPA (Tissue-Type Plasminogen Activator) Eligible Stroke
      Patients With Proximal Intracranial Occlusions.

PMID- 29212749
TI  - Treating hummingbirds as feathered bees: a case of ethological cross-pollination.
AB  - Hummingbirds feed from hundreds of flowers every day. The properties of these
      flowers provide these birds with a wealth of information about colour, space and
      time to guide how they forage. To understand how hummingbirds might use this
      information, researchers have adapted established laboratory paradigms for use in
      the field. In recent years, however, experimental inspiration has come less from
      other birds, and more from looking at other nectar-feeders, particularly
      honeybees and bumblebees, which have been models for foraging behaviour and
      cognition for over a century. In a world in which the cognitive abilities of bees
      regularly make the news, research on the influence of ecology and sensory systems
      on bee behaviour is leading to novel insights in hummingbird cognition. As
      methods designed to study insects in the laboratory are being applied to
      hummingbirds in the field, converging methods can help us identify and understand
      convergence in cognition, behaviour and ecology.

PMID- 29212751
TI  - Heterothermy is associated with reduced fitness in wild rabbits.
AB  - An increase in variation in the 24 h pattern of body temperature (heterothermy)
      in mammals can be induced by energy and water deficits. Since performance traits
      such as growth and reproduction also are impacted by energy and water balance, we
      investigated whether the characteristics of the body temperature rhythm provide
      an indication of the reproductive success of an individual. We show that the
      amplitude of the daily rhythm of body temperature in wild rabbits (Oryctolagus
      cuniculus) prior to breeding is inversely related to the number of pregnancies in
      the subsequent seven months, while the minimum daily body temperature is
      positively correlated to the number of pregnancies. Because reproductive output
      could be predicted from characteristics of the core body temperature rhythm prior
      to the breeding season, we propose that the pattern of the 24 h body temperature
      rhythm could provide an index of animal fitness in a given environment.

PMID- 29212750
TI  - Does oxidative stress shorten telomeres in vivo? A review.
AB  - The length of telomeres, the protective caps of chromosomes, is increasingly used
      as a biomarker of individual health state because it has been shown to predict
      chances of survival in a range of endothermic species including humans. Oxidative
      stress is presumed to be a major cause of telomere shortening, but most evidence
      to date comes from in vitro cultured cells. The importance of oxidative stress as
      a determinant of telomere shortening in vivo remains less clear and has recently
      been questioned. We, therefore, reviewed correlative and experimental studies
      investigating the links between oxidative stress and telomere shortening in vivo
      While correlative studies provide equivocal support for a connection between
      oxidative stress and telomere attrition (10 of 18 studies), most experimental
      studies published so far (seven of eight studies) partially or fully support this
      hypothesis. Yet, this link seems to be tissue-dependent in some cases, or
      restricted to particular categories of individual (e.g. sex-dependent) in other
      cases. More experimental studies, especially those decreasing antioxidant
      protection or increasing pro-oxidant generation, are required to further our
      understanding of the importance of oxidative stress in determining telomere
      length in vivo Studies comparing growing versus adult individuals, or
      proliferative versus non-proliferative tissues would provide particularly
      important insights.

PMID- 29212752
TI  - Freezer on, lights off! Environmental effects on activity rhythms of fish in the
      Arctic.
AB  - Polar regions are characterized by acute seasonal changes in the environment,
      with organisms inhabiting these regions lacking diel photoperiodic information
      for parts of the year. We present, to our knowledge, the first high-resolution
      analysis of diel and seasonal activity of free-living fishes in polar waters (74
      degrees N), subject to extreme variation in photoperiod, temperature and food
      availability. Using biotelemetry, we tracked two sympatric ecomorphs of lake
      dwelling Arctic charr (Salvelinus alpinus n = 23) over an annual cycle. Charr
      activity rhythms reflected the above-surface photoperiod (including under ice),
      with diel rhythms of activity observed. During the dark winter solstice period,
      charr activity became arrhythmic and much reduced, even though estimated light
      levels were within those at which charr can feed. When twilight resumed, charr
      activity ensued as diel vertical migration, which continued throughout spring and
      with increasing day length, despite stable water temperatures. Diel activity
      rhythms ceased during the polar day, with a sharp increase in arrhythmic fish
      activity occurring at ice-break. Despite contrasting resource use, circannual
      rhythms were mirrored in the two ecomorphs, although individual variability in
      activity rhythms was evident. Our data support conclusions of functionally
      adaptive periods of arrhythmicity in polar animals, suggesting maintenance of a
      circannual oscillator for scheduling seasonal behavioural and developmental
      processes.

PMID- 29212753
TI  - Water vascular system architecture in an Ordovician ophiuroid.
AB  - Understanding the water vascular system (WVS) in early fossil echinoderms is
      critical to elucidating the evolution of this system in extant forms. Here we
      present the first report of the internal morphology of the water vascular system
      of a stem ophiuroid. The radial canals are internal to the arm, but protected
      dorsally by a plate separate to the ambulacrals. The canals zig-zag with no
      evidence of constrictions, corresponding to sphincters, which control pairs of
      tube feet in extant ophiuroids. The morphology suggests that the unpaired tube
      feet must have operated individually, and relied on the elasticity of the radial
      canals, lateral valves and tube foot musculature alone for extension and
      retraction. This arrangement differs radically from that in extant ophiuroids,
      revealing a previously unknown Palaeozoic configuration.

PMID- 29212754
TI  - Graph-facilitated resonant mode counting in stochastic interaction networks.
AB  - Oscillations in dynamical systems are widely reported in multiple branches of
      applied mathematics. Critically, even a non-oscillatory deterministic system can
      produce cyclic trajectories when it is in a low copy number, stochastic regime.
      Common methods of finding parameter ranges for stochastically driven resonances,
      such as direct calculation, are cumbersome for any but the smallest networks. In
      this paper, we provide a systematic framework to efficiently determine the number
      of resonant modes and parameter ranges for stochastic oscillations relying on
      real root counting algorithms and graph theoretic methods. We argue that
      stochastic resonance is a network property by showing that resonant modes only
      depend on the squared Jacobian matrix J2, unlike deterministic oscillations which
      are determined by J By using graph theoretic tools, analysis of stochastic
      behaviour for larger interaction networks is simplified and stochastic dynamical
      systems with multiple resonant modes can be identified easily.

PMID- 29212755
TI  - Model-based image analysis of a tethered Brownian fibre for shear stress sensing.
AB  - The measurement of fluid dynamic shear stress acting on a biologically relevant
      surface is a challenging problem, particularly in the complex environment of, for
      example, the vasculature. While an experimental method for the direct detection
      of wall shear stress via the imaging of a synthetic biology nanorod has recently
      been developed, the data interpretation so far has been limited to
      phenomenological random walk modelling, small-angle approximation, and image
      analysis techniques which do not take into account the production of an image
      from a three-dimensional subject. In this report, we develop a mathematical and
      statistical framework to estimate shear stress from rapid imaging sequences based
      firstly on stochastic modelling of the dynamics of a tethered Brownian fibre in
      shear flow, and secondly on a novel model-based image analysis, which
      reconstructs fibre positions by solving the inverse problem of image formation.
      This framework is tested on experimental data, providing the first
      mechanistically rational analysis of the novel assay. What follows further
      develops the established theory for an untethered particle in a semi-dilute
      suspension, which is of relevance to, for example, the study of Brownian
      nanowires without flow, and presents new ideas in the field of multi-disciplinary
      image analysis.

PMID- 29212757
TI  - The tactile perception of transient changes in friction.
AB  - When we touch an object or explore a texture, frictional strains are induced by
      the tactile interactions with the surface of the object. Little is known about
      how these interactions are perceived, although it becomes crucial for the nascent
      industry of interactive displays with haptic feedback (e.g. smartphones and
      tablets) where tactile feedback based on friction modulation is particularly
      relevant. To investigate the human perception of frictional strains, we mounted a
      high-fidelity friction modulating ultrasonic device on a robotic platform
      performing controlled rubbing of the fingertip and asked participants to detect
      induced decreases of friction during a forced-choice task. The ability to
      perceive the changes in friction was found to follow Weber's Law of just
      noticeable differences, as it consistently depended on the ratio between the
      reduction in tangential force and the pre-stimulation tangential force. The Weber
      fraction was 0.11 in all conditions demonstrating a very high sensitivity to
      transient changes in friction. Humid fingers experienced less friction reduction
      than drier ones for the same intensity of ultrasonic vibration but the Weber
      fraction for detecting changes in friction was not influenced by the humidity of
      the skin.

PMID- 29212756
TI  - The interaction between electromagnetic fields at megahertz, gigahertz and
      terahertz frequencies with cells, tissues and organisms: risks and potential.
AB  - Since regular radio broadcasts started in the 1920s, the exposure to human-made
      electromagnetic fields has steadily increased. These days we are not only exposed
      to radio waves but also other frequencies from a variety of sources, mainly from
      communication and security devices. Considering that nearly all biological
      systems interact with electromagnetic fields, understanding the affects is
      essential for safety and technological progress. This paper systematically
      reviews the role and effects of static and pulsed radio frequencies (100-109 Hz),
      millimetre waves (MMWs) or gigahertz (109-1011 Hz), and terahertz (1011-1013 Hz)
      on various biomolecules, cells and tissues. Electromagnetic fields have been
      shown to affect the activity in cell membranes (sodium versus potassium ion
      conductivities) and non-selective channels, transmembrane potentials and even the
      cell cycle. Particular attention is given to millimetre and terahertz radiation
      due to their increasing utilization and, hence, increasing human exposure. MMWs
      are known to alter active transport across cell membranes, and it has been
      reported that terahertz radiation may interfere with DNA and cause genomic
      instabilities. These and other phenomena are discussed along with the
      discrepancies and controversies from published studies.

PMID- 29212758
TI  - Membrane capacitance of thousands of single white blood cells.
AB  - As label-free biomarkers, the electrical properties of single cells are widely
      used for cell type classification and cellular status evaluation. However, as
      intrinsic cellular electrical markers, previously reported membrane capacitances
      (e.g. specific membrane capacitance Cspec and total membrane capacitance Cmem) of
      white blood cells were derived from tens of single cells, lacking statistical
      significance due to low cell numbers. In this study, white blood cells were first
      separated into granulocytes and lymphocytes by density gradient centrifugation
      and were then aspirated through a microfluidic constriction channel to
      characterize both Cspec and Cmem Thousands of granulocytes (ncell = 3327) and
      lymphocytes (ncell = 3302) from 10 healthy blood donors were characterized,
      resulting in Cspec values of 1.95 +/- 0.22 uF cm-2 versus 2.39 +/- 0.39 uF cm-2
      and Cmem values of 6.81 +/- 1.09 pF versus 4.63 +/- 0.57 pF. Statistically
      significant differences between granulocytes and lymphocytes were located for
      both Cspec and Cmem In addition, neural network-based pattern recognition was
      used to classify white blood cells, producing successful classification rates of
      78.1% for Cspec and 91.3% for Cmem, respectively. These results indicate that as
      intrinsic bioelectrical markers, membrane capacitances may contribute to the
      classification of white blood cells.

PMID- 29212759
TI  - Navigating features: a topologically informed chart of electromyographic features
      space.
AB  - The success of biological signal pattern recognition depends crucially on the
      selection of relevant features. Across signal and imaging modalities, a large
      number of features have been proposed, leading to feature redundancy and the need
      for optimal feature set identification. A further complication is that, due to
      the inherent biological variability, even the same classification problem on
      different datasets can display variations in the respective optimal sets, casting
      doubts on the generalizability of relevant features. Here, we approach this
      problem by leveraging topological tools to create charts of features spaces.
      These charts highlight feature sub-groups that encode similar information (and
      their respective similarities) allowing for a principled and interpretable choice
      of features for classification and analysis. Using multiple electromyographic
      (EMG) datasets as a case study, we use this feature chart to identify functional
      groups among 58 state-of-the-art EMG features, and to show that they generalize
      across three different forearm EMG datasets obtained from able-bodied subjects
      during hand and finger contractions. We find that these groups describe
      meaningful non-redundant information, succinctly recapitulating information about
      different regions of feature space. We then recommend representative features
      from each group based on maximum class separability, robustness and minimum
      complexity.

PMID- 29212760
TI  - Large-scale molecular dynamics simulation of coupled dynamics of flow and
      glycocalyx: towards understanding atomic events on an endothelial cell surface.
AB  - The glycocalyx has a prominent role in orchestrating multiple biological
      processes occurring at the plasma membrane. In this paper, an all-atom
      flow/glycocalyx system is constructed with the bulk flow velocity in the
      physiologically relevant ranges for the first time. The system is simulated by
      molecular dynamics using 5.8 million atoms. Flow dynamics and statistics in the
      presence of the glycocalyx are presented and discussed. Complex dynamic
      behaviours of the glycocalyx, particularly the sugar chains, are observed in
      response to blood flow. In turn, the motion of the glycocalyx, including swing
      and swirling, disturbs the flow by altering the velocity profiles and modifying
      the vorticity distributions. As a result, the initially one-dimensional forcing
      is spread to all directions in the region near the endothelial cell surface.
      Furthermore, the coupled dynamics exist not only between the flow and the
      glycocalyx but also within the glycocalyx molecular constituents. Shear stress
      distributions between one-dimer and three-dimer cases are also conducted.
      Finally, potential force transmission pathways are discussed based on the
      dynamics of the glycocalyx constituents, which provides new insight into the
      mechanism of mechanotransduction of the glycocalyx. These findings have relevance
      in the pathologies of glycocalyx-related diseases, for example in renal or
      cardiovascular conditions.

PMID- 29212761
TI  - Care UK tells GPs about private options for non-NHS funded procedures.

PMID- 29212762
TI  - It is merely subjective opinion that patient-reported outcome measures are not
      objective tools.

PMID- 29212763
TI  - Perinatal pathologists have a vital role in stillbirth review.

PMID- 29212764
TI  - Aberrant DNA methylation of pregnane X receptor underlies metabolic gene
      alterations in the diabetic kidney.
AB  - Epigenetic abnormalities have been suggested to mediate metabolic memory observed
      in diabetic complications. We have shown that epigenetic alterations may induce
      persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In
      this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear
      receptor, is epigenetically altered and upregulated and may have a possible
      function in the diabetic kidney. PXR has been shown to play a critical role in
      metabolic changes in obesity and diabetes; however, its distribution and function
      in the kidney are unknown. In the normal kidney, Pxr was selectively expressed in
      the proximal tubular cells with demethylation in the promoter DNA. In db/db mice,
      significant increases in Pxr mRNA, further demethylation of DNA, and stimulatory
      histone marks in the promoter were observed. Epigenetic changes are likely to
      play a causative role in PXR induction, since a DNA methyltransferase inhibitor
      increased PXR mRNA in cultured human proximal tubular cells. Administration of a
      PXR agonist increased mRNA levels of solute carrier organic anion transporter
      family member 2B1 ( Slco2b1), a xenobiotic transporter; response gene to
      complement 32 ( Rgc32), a molecule known to exert fibrotic effects in the kidney;
      and phosphoenolpyruvate carboxykinase 1 ( Pck1), a gluconeogenic enzyme in the
      kidney. The expressions of these genes were inhibited by PXR small interfering
      RNA in cultured proximal tubular cells. Increased mRNA levels of Slco2b1, Rgc32,
      and Pck1 were also observed in the kidney of db/db mice. These data indicate that
      PXR is upregulated in the diabetic kidney with aberrant epigenetic modifications
      and may modulate the course of diabetic kidney disease through the activation of
      these genes.

PMID- 29212765
TI  - Changes in the fluid volume balance between intra- and extracellular water in a
      sample of Japanese adults aged 15-88 yr old: a cross-sectional study.
AB  - The fluid volume balance between intracellular water (ICW) and extracellular
      water (ECW) gradually changes with age and various medical conditions.
      Comprehension of these physiological changes would aid in clinical decision
      making related to body fluid assessments. A total of 1,992 individuals (753 men
      and 1,239 women) aged >=15 yr included in this study had their body composition
      measurements performed at training gyms in 2014. We developed a regression
      formula to assess the association of age with the ratio of ECW to ICW in these
      subjects. The mean ages of male and female subjects were 51.2 +/- 15.2 and 57.4
      +/- 15.2 yr, and their mean body mass indexes were 23.4 +/- 3.3 and 21.1 +/- 2.8
      kg/m2, respectively. The total fluid volumes of male and female subjects were
      39.6 +/- 4.9 and 27.7 +/- 3.0 liters, whereas the percent body fat mass per
      kilogram of body weight were 19 and 26%, respectively. The ECW-to-ICW ratio
      increased with age because of the steeper decrease in the ICW content than in the
      ECW content, especially after the age of 70 yr. The regression formulas used for
      calculating the age-adjusted ECW/ICW ratio were as follows: 0.5857 + 7.4334 * 10
      6 * (age)2 in men and 0.6062 + 5.5775 * 10-6 * (age)2 in women. In conclusion,
      the fluid imbalance between ICW and ECW contents is driven by decreased cell
      volume associated with aging and muscle attenuation. Therefore, our proposed
      formula may serve as a useful assessment tool for the calculation of body fluid
      composition.

PMID- 29212766
TI  - Bright spots, physical activity investments that work: Active Everyday,
      Sheffield's physical activity service for all people living with and beyond
      cancer.

PMID- 29212767
TI  - Passifloraceae seeds from the late Eocene of Colombia.
AB  - PREMISE OF THE STUDY: The plant fossil record for the neotropics is still sparse
      and temporally discontinuous. The location and description of new fossil material
      are fundamental for understanding evolutionary and biogeographic patterns of
      lineages. A new fossil record of Passifloraceae from the late Eocene of Colombia
      is described in this study. METHODS: Plant fossils were collected from a new
      locality from the Eocene Esmeraldas Formation. Eighteen fossil seeds were
      selected, described, and compared with fossil and extant angiosperm seeds based
      on the literature and herbarium collections. Taxonomic affinities of the fossil
      seeds within Passifloraceae s.l. were evaluated by comparing morphological
      characters of the seeds in a phylogenetic context. Stratigraphic information
      associated with the fossil locality was used to interpret the environment and
      taphonomic processes associated with fossil deposition. KEY RESULTS: A new seed
      fossil genus and species, Passifloroidesperma sogamosense gen. and sp. nov., is
      described and associated with the subfamily Passifloroideae based on the presence
      of a foveolate seed surface, ruminate endosperm, and a seed coat with prismatic
      palisade cells. The depositional environment of the locality is described as a
      floodplain associated with river channels. CONCLUSIONS: A detailed review of the
      Passifloraceae fossil record indicates that P. sogamosense is the oldest
      confirmed record of Passifloraceae. Its late Eocene age provides a minimum age
      that can be used as a calibration point for the crown Passifloroideae node in
      future dating analyses that together with its neotropical geographic location can
      shed light on the origin and diversification of the subfamily.

PMID- 29212768
TI  - Evolutionary history of two pollen self-incompatibility factors reveals alternate
      routes to self-compatibility within Solanum.
AB  - PREMISE OF THE STUDY: Self-incompatibility (SI) prevents self-fertilization and
      reduces inbreeding. While SI is common in plants, transitions to self
      compatibility (SC) occur frequently. Little is known about the genetic changes
      and evolutionary steps underlying these shifts. METHODS: In the Solanaceae, SI is
      gametophytic, with specificity determined by S-RNases in the pistil and S-locus F
      box proteins (SLFs) in pollen. We examined the role of two pollen factors,
      Cullin1 (CUL1) and SLF-23, in SI -> SC transitions in wild tomato species from
      the Arcanum species group (Solanum arcanum, S. neorickii, and S. chmielewskii).
      Pollen compatibility was assessed on tester lines that reject pollen lacking
      functional SLF-23 or CUL1. Complementation tests, gene sequencing, and
      phylogenetic analyses were used to characterize both functional and nonfunctional
      alleles. KEY RESULTS: We found evidence for multiple independent SI -> SC
      transitions. In S. arcanum and S. chmielewskii, SC is caused by loss of pistil S
      RNase activity, while in S. neorickii SC is associated with expression of a
      functional SLF-23 that recognizes the S9 type S-RNase expressed in its pistils.
      Interestingly, we found identical deletion mutations in CUL1 exon 7 of S.
      chmielewskii as previously seen in S. habrochaites. CONCLUSIONS: Mating system
      transitions in the Arcanum group have occurred via both pistil loss-of-function
      and pollen gain-of-function SC mutations. Mutations common to S. chmielewskii and
      S. habrochaites must have arisen in a common ancestor, possibly to the entire
      tomato clade, then became fixed in different lineages after loss of pistil-side
      SI function.

PMID- 29212769
TI  - Functional and structural characterization of a novel malignant hyperthermia
      susceptible variant of DHPR-beta1a subunit (CACNB1).
AB  - Malignant hyperthermia (MH) susceptibility has been recently linked to a novel
      variant of beta1a subunit of the dihydropyridine receptor (DHPR), a channel
      essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of
      the mutant variant V156A on the structure/function of DHPR beta1a subunit and
      assess its role on Ca2+ metabolism of cultured myotubes. Using differential
      scanning fluorimetry, we show that mutation V156A causes a significant reduction
      in thermal stability of the Src homology 3/guanylate kinase core domain of beta1a
      subunit. Expression of the variant subunit in beta1-null mouse myotubes resulted
      in increased sensitivity to caffeine stimulation. Whole cell patch-clamp analysis
      of beta1a-V156A-expressing myotubes revealed a -2 mV shift in voltage dependence
      of channel activation, but no changes in Ca2+ conductance, current kinetics, or
      sarcoplasmic reticulum Ca2+ load were observed. Measurement of resting free Ca2+
      and Na+ concentrations shows that both cations were significantly elevated in
      beta1a-V156A-expressing myotubes and that these changes were linked to increased
      rates of plasmalemmal Ca2+ entry through Na+/Ca2+ exchanger and/or transient
      receptor potential canonical channels. Overall, our data show that mutant variant
      V156A results in instability of protein subdomains of beta1a subunit leading to a
      phenotype of Ca2+ dysregulation that partly resembles that of other MH-linked
      mutations of DHPR alpha1S subunit. These data prove that homozygous expression of
      variant beta1a-V156A has the potential to be a pathological variant, although it
      may require other gene defects to cause a full MH phenotype.

PMID- 29212770
TI  - Breast cancer screening.

PMID- 29212771
TI  - Establishment of a surgical bile duct injection technique giving direct access to
      the bile ducts for studies of the murine biliary tree.
AB  - Cholangiopathies are progressive disorders with largely unknown pathoetiology and
      limited treatment options. We aimed to develop a novel surgical technique with
      direct access to the bile ducts that would complement existing mouse models of
      cholestasis, biliary inflammation, and fibrosis and present a new route of
      administration for testing of potential treatment strategies. We developed a
      surgical technique to access the murine biliary tree by injection of different
      solvents through catheterization of the gall bladder with simultaneous clamping
      of the common bile duct. To demonstrate the applicability of the technique, we
      injected either phosphate-buffered saline or dimethyl sulfoxide in concentrations
      of 50 or 65% and compared these groups with sham-operated mice. The surgery was
      optimized to achieve a mortality rate close to 0. There were no significant
      changes in pain, activity level, or mortality from the day of the surgery until
      euthanization for any groups. Injection of phosphate-buffered saline or 50%
      dimethyl sulfoxide was generally well-tolerated, whereas 65% dimethyl sulfoxide
      led to higher weight loss, an increase of serum alanine transaminase, and
      histological portal inflammation. There were no signs of inflammation in the gut.
      We have developed a bile duct injection technique that is well-tolerated, easily
      reproducible, and that may complement existing models of cholangiopathies. Direct
      access to the bile ducts without causing harm to the hepatobiliary or intestinal
      tissue may be valuable in future studies of normal biliary physiology and
      different pathophysiological mechanisms of disease and to test novel therapeutic
      strategies. NEW & NOTEWORTHY To evaluate tolerability of the bile duct to
      injection of both polar and nonpolar compounds, we established a novel biliary
      injection technique. This technique is well-tolerated, easily reproducible, and
      with direct access to the bile ducts for studies of the murine biliary tree. The
      bile duct injection technique may complement existing animal models and be a
      valuable tool in future studies of normal biliary physiology or pathophysiology
      and to test novel therapeutic strategies.

PMID- 29212773
TI  - Opioids are not just an American problem.

PMID- 29212774
TI  - Government must create foundation training places for 1500 new medical students,
      says BMA.

PMID- 29212772
TI  - Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis.
AB  - OBJECTIVE: To determine which potentially modifiable risk factors, including
      socioeconomic, lifestyle/dietary, cardiometabolic, and inflammatory factors, are
      associated with Alzheimer's disease. DESIGN: Mendelian randomisation study using
      genetic variants associated with the modifiable risk factors as instrumental
      variables. SETTING: International Genomics of Alzheimer's Project. PARTICIPANTS:
      17 008 cases of Alzheimer's disease and 37 154 controls. MAIN OUTCOME MEASURES:
      Odds ratio of Alzheimer's per genetically predicted increase in each modifiable
      risk factor estimated with Mendelian randomisation analysis. RESULTS: This study
      included analyses of 24 potentially modifiable risk factors. A Bonferroni
      corrected threshold of P=0.002 was considered to be significant, and P<0.05 was
      considered suggestive of evidence for a potential association. Genetically
      predicted educational attainment was significantly associated with Alzheimer's.
      The odds ratios were 0.89 (95% confidence interval 0.84 to 0.93; P=2.4*10-6) per
      year of education completed and 0.74 (0.63 to 0.86; P=8.0*10-5) per unit increase
      in log odds of having completed college/university. The correlated trait
      intelligence had a suggestive association with Alzheimer's (per genetically
      predicted 1 SD higher intelligence: 0.73, 0.57 to 0.93; P=0.01). There was
      suggestive evidence for potential associations between genetically predicted
      higher quantity of smoking (per 10 cigarettes a day: 0.69, 0.49 to 0.99; P=0.04)
      and 25-hydroxyvitamin D concentrations (per 20% higher levels: 0.92, 0.85 to
      0.98; P=0.01) and lower odds of Alzheimer's and between higher coffee consumption
      (per one cup a day: 1.26, 1.05 to 1.51; P=0.01) and higher odds of Alzheimer's.
      Genetically predicted alcohol consumption, serum folate, serum vitamin B12,
      homocysteine, cardiometabolic factors, and C reactive protein were not associated
      with Alzheimer's disease. CONCLUSION: These results provide support that higher
      educational attainment is associated with a reduced risk of Alzheimer's disease.

PMID- 29212775
TI  - A centenary of health campaigns.

PMID- 29212776
TI  - Plans to boost cancer workforce are "scratching the surface," says radiology
      leader.

PMID- 29212777
TI  - Detection and monitoring of circulating tumor DNA in adrenocortical carcinoma.

PMID- 29212778
TI  - Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic
      Architecture of Coronary Artery Disease.
AB  - RATIONALE: Coronary artery disease (CAD) is a complex phenotype driven by genetic
      and environmental factors. Ninety-seven genetic risk loci have been identified to
      date, but the identification of additional susceptibility loci might be important
      to enhance our understanding of the genetic architecture of CAD. OBJECTIVE: To
      expand the number of genome-wide significant loci, catalog functional insights,
      and enhance our understanding of the genetic architecture of CAD. METHODS AND
      RESULTS: We performed a genome-wide association study in 34 541 CAD cases and 261
      984 controls of UK Biobank resource followed by replication in 88 192 cases and
      162 544 controls from CARDIoGRAMplusC4D. We identified 75 loci that replicated
      and were genome-wide significant (P<5*10-8) in meta-analysis, 13 of which had not
      been reported previously. Next, to further identify novel loci, we identified all
      promising (P<0.0001) loci in the CARDIoGRAMplusC4D data and performed reciprocal
      replication and meta-analyses with UK Biobank. This led to the identification of
      21 additional novel loci reaching genome-wide significance (P<5*10-8) in meta
      analysis. Finally, we performed a genome-wide meta-analysis of all available data
      revealing 30 additional novel loci (P<5*10-8) without further replication. The
      increase in sample size by UK Biobank raised the number of reconstituted gene
      sets from 4.2% to 13.9% of all gene sets to be involved in CAD. For the 64 novel
      loci, 155 candidate causal genes were prioritized, many without an obvious
      connection to CAD. Fine mapping of the 161 CAD loci generated lists of credible
      sets of single causal variants and genes for functional follow-up. Genetic risk
      variants of CAD were linked to development of atrial fibrillation, heart failure,
      and death. CONCLUSIONS: We identified 64 novel genetic risk loci for CAD and
      performed fine mapping of all 161 risk loci to obtain a credible set of causal
      variants. The large expansion of reconstituted gene sets argues in favor of an
      expanded omnigenic model view on the genetic architecture of CAD.

PMID- 29212779
TI  - Longitudinal Analysis of Genetic Susceptibility and BMI Throughout Adult Life.
AB  - Little is known about the genetic influence on BMI trajectory throughout
      adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI
      associated variants among 9,971 women and 6,405 men of European ancestry. Serial
      measures of BMI were assessed from 18 (women) or 21 (men) years to 85 years of
      age. We also examined BMI change in early (from 18 or 21 to 45 years of age),
      middle (from 45 to 65 years of age), and late adulthood (from 65 to 80 years of
      age). GRS was positively associated with BMI across all ages, with stronger
      associations in women than in men. The associations increased from early to
      middle adulthood, peaked at 45 years of age in men and at 60 years of age in
      women (0.91 and 1.35 kg/m2 per 10-allele increment, respectively) and
      subsequently declined in late adulthood. For women, each 10-allele increment in
      the GRS was associated with an average BMI gain of 0.54 kg/m2 in early adulthood,
      whereas no statistically significant association was found for BMI change in
      middle or late adulthood or for BMI change in any life period in men. Our
      findings indicate that genetic predisposition exerts a persistent effect on
      adiposity throughout adult life and increases early adulthood weight gain in
      women.

PMID- 29212780
TI  - Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic
      Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin
      in Diabetic Rats.
AB  - Diabetes mellitus (DM) is associated with increased plasma levels of arginine
      vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However,
      the mechanisms by which DM may cause the increased AVP levels are not known.
      Electrophysiological recordings in supraoptic nucleus (SON) slices from
      streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed
      that gamma-aminobutyric acid (GABA) functions generally as an excitatory
      neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes
      inhibitory responses in the cells of control animals. Furthermore, Western
      blotting analyses of Cl- transporters in the SON tissues indicated that Na+-K+
      2Cl- cotransporter isotype 1 (a Cl- importer) was upregulated and K+-Cl-
      cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats.
      Treatment with CLP290 (a KCC2 activator) significantly lowered blood AVP and
      glucose levels in STZ rats. Last, investigation that used rats expressing an AVP
      enhanced green fluorescent protein fusion gene showed that AVP synthesis in AVP
      neurons was much more intense in STZ rats than in control rats. We conclude that
      altered Cl- homeostasis that makes GABA excitatory and enhanced AVP synthesis are
      important changes in AVP neurons that would increase AVP secretion in DM. Our
      data suggest that Cl- transporters in AVP neurons are potential targets of
      antidiabetes treatments.

PMID- 29212781
TI  - Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.
AB  - Immune checkpoint inhibitors have unique toxicities and response kinetics
      compared with cytotoxic and gene-targeted anticancer agents. We investigated the
      impact of innovative/accelerated immunotherapy drug development/approval models
      on the accuracy of safety and efficacy assessments by searching the FDA website.
      Initial phase I trials for each agent were reviewed and safety and efficacy data
      compared with that found in later trials leading to regulatory approvals of the
      same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a
      variety of cancer types. All checkpoint inhibitors received a priority review
      status and access to at least two additional FDA special access programs, more
      often breakthrough therapy designation and accelerated approval. Median clinical
      development time (investigational new drug application to approval) was 60.77
      months [avelumab had the shortest timeline (52.33 months)]. Response rates during
      early phase I trials (median = 16%) are higher than for phase I trials of other
      agents (with the exception of gene-targeted agents tested with a biomarker).
      Doses approved were usually not identical to doses recommended on phase I trials.
      Approximately 50% of types of immune-related and 43% of types of clinically
      relevant toxicities from later trials were identified in early-phase trials. Even
      so, treatment-related mortality remains exceedingly low in later studies (0.33%
      of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors
      appear to be reasonably predicted from the dose-finding portion of phase I
      trials, indicating that the fast-track development of these agents is safe and
      justified. Clin Cancer Res; 24(8); 1785-94. (c)2017 AACR.

PMID- 29212783
TI  - Shared care protocols - have they had their day?

PMID- 29212782
TI  - Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic
      database review of the US FDA approval process.
AB  - INTRODUCTION: Transvaginal mesh devices are approved in the USA by the Food and
      Drug Administration (FDA), through the 510(k) system. However, there is
      uncertainty about the benefit to harm balance of mesh approved for pelvic organ
      prolapse. We, therefore, assessed the evidence at the time of approval for
      transvaginal mesh products and the impact of safety studies the FDA mandated in
      2012 because of emerging harms. METHODS: We used FDA databases to determine the
      evidence for approval of transvaginal mesh. To create a 'family tree' of device
      equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh
      (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all
      subsequently related device approvals, and for the first published randomised
      trial evidence. We assessed compliance with all FDA 522 orders issued in 2012
      requiring postmarketing surveillance studies. RESULTS: We found 61 devices whose
      approval ultimately relied on claimed equivalence to the Mersilene Mesh and the
      ProteGen Sling. We found no clinical trials evidence for these 61 devices at the
      time of approval. Publication of randomised clinical trials occurred at a median
      of 5 years after device approval (range 1-14 years). Analysis of 119 FDA 522
      orders revealed that in 79 (66%) the manufacturer ceased market distribution of
      the device, and in 26 (22%) the manufacturer had changed the indication. Only
      seven studies (six cohorts and new randomised controlled trial) covering 11
      orders were recruiting participants (none had reported outcomes). CONCLUSIONS:
      Transvaginal mesh products for pelvic organ prolapse have been approved on the
      basis of weak evidence over the last 20 years. Devices have inherited approval
      status from a few products. A publicly accessible registry of licensed invasive
      devices, with details of marketing status and linked evidence, should be created
      and maintained at the time of approval.

PMID- 29212785
TI  - Brief history of the specialty of emergency medicine.
AB  - This is a brief overview of the development of the specialty of Emergency
      Medicine from small beginnings fifty years ago. It describes how the specialty
      evolved simultaneously in the UK and the USA and later in Australasia and Europe.

PMID- 29212784
TI  - An oligoclonal antibody durably overcomes resistance of lung cancer to third
      generation EGFR inhibitors.
AB  - Epidermal growth factor receptor (EGFR) mutations identify patients with lung
      cancer who derive benefit from kinase inhibitors. However, most patients
      eventually develop resistance, primarily due to the T790M second-site mutation.
      Irreversible inhibitors (e.g., osimertinib/AZD9291) inhibit T790M-EGFR, but
      several mechanisms, including a third-site mutation, C797S, confer renewed
      resistance. We previously reported that a triple mixture of monoclonal
      antibodies, 3*mAbs, simultaneously targeting EGFR, HER2, and HER3, inhibits T790M
      expressing tumors. We now report that 3*mAbs, including a triplet containing
      cetuximab and trastuzumab, inhibits C797S-expressing tumors. Unlike osimertinib,
      which induces apoptosis, 3*mAbs promotes degradation of the three receptors and
      induces cellular senescence. Consistent with distinct mechanisms, treatments
      combining 3*mAbs plus sub-inhibitory doses of osimertinib synergistically and
      persistently eliminated tumors. Thus, oligoclonal antibodies, either alone or in
      combination with kinase inhibitors, might preempt repeated cycles of treatment
      and rapid emergence of resistance.

PMID- 29212786
TI  - Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced
      neuronal apoptosis and cognitive decline in mice.
AB  - Diabetes mellitus is a significant global public health problem depicting a
      rising prevalence worldwide. As a serious complication of diabetes, diabetes
      associated cognitive decline is attracting increasing attention. However, the
      underlying mechanisms are yet to be fully determined. Both endoplasmic reticulum
      (ER) stress and autophagy have been reported to modulate neuronal survival and
      death and be associated with several neurodegenerative diseases. Here, a
      streptozotocin-induced diabetic mouse model and primary cultured mouse
      hippocampal neurons were employed to investigate the possible role of ER stress
      and autophagy in diabetes-induced neuronal apoptosis and cognitive impairments,
      and further explore the potential molecular mechanisms. ER stress markers GRP78
      and CHOP were both enhanced in diabetic mice, as was phosphorylation of PERK,
      IRE1alpha, and JNK. In addition, the results indicated an elevated level of
      autophagy in diabetic mice, as demonstrated by up-regulated expressions of
      autophagy markers LC3-II, beclin 1 and down-regulated level of p62, and increased
      formation of autophagic vacuoles and LC3-II aggregates. Meanwhile, we found that
      these effects could be abolished by ER stress inhibitor 4-phenylbutyrate or JNK
      inhibitor SP600125 in vitro. Furthermore, neuronal apoptosis of diabetic mice was
      attenuated by pretreatment with 4-phenylbutyrate, while aggravated by application
      of inhibitor of autophagy bafilomycin A1 in vitro. These results suggest that ER
      stress pathway may be involved in diabetes-mediated neurotoxicity and promote the
      following cognitive impairments. More important, autophagy was induced by
      diabetes possibly through ER stress-mediated JNK pathway, which may protect
      neurons against ER stress-associated cell damages.

PMID- 29212787
TI  - Parent-infant room-sharing is complex and important for breastfeeding.

PMID- 29212788
TI  - L-methylfolate cannot yet be recommended as an add-on treatment in schizophrenia.

PMID- 29212790
TI  - The Arp2/3 Regulatory System and Its Deregulation in Cancer.
AB  - The Arp2/3 complex is an evolutionary conserved molecular machine that generates
      branched actin networks. When activated, the Arp2/3 complex contributes the actin
      branched junction and thus cross-links the polymerizing actin filaments in a
      network that exerts a pushing force. The different activators initiate branched
      actin networks at the cytosolic surface of different cellular membranes to
      promote their protrusion, movement, or scission in cell migration and membrane
      traffic. Here we review the structure, function, and regulation of all the direct
      regulators of the Arp2/3 complex that induce or inhibit the initiation of a
      branched actin network and that controls the stability of its branched junctions.
      Our goal is to present recent findings concerning novel inhibitory proteins or
      the regulation of the actin branched junction and place these in the context of
      what was previously known to provide a global overview of how the Arp2/3 complex
      is regulated in human cells. We focus on the human set of Arp2/3 regulators to
      compare normal Arp2/3 regulation in untransformed cells to the deregulation of
      the Arp2/3 system observed in patients affected by various cancers. In many
      cases, these deregulations promote cancer progression and have a direct impact on
      patient survival.

PMID- 29212791
TI  - Perinatal inflammation induces sex-related differences in cardiovascular
      morbidities in mice.
AB  - Sex-related differences in cardiovascular health and disease have been
      identified, with males having a higher incidence of cardiovascular events but
      females more likely to develop arrhythmias. Adverse fetal environments are now
      accepted as a cause for the development of cardiovascular diseases in adulthood,
      but sex-related differences in response to adverse fetal environments have not
      been extensively explored. The combination of both in utero and postnatal
      exposure to inflammation is highly relevant for the infant that is born preterm
      or has clinical complications at birth or in early postnatal life. We have
      previously observed cardiac contractile deficiencies and dysregulation of Ca2+
      handling proteins in our model of maternal lipopolysaccharide (LPS) and neonatal
      hyperoxia exposures (LPS/O2). This investigation tested the hypothesis that there
      are sex-related differences in the adult pathologies after exposure to perinatal
      inflammation. Using pressure-volume assessments, males exposed to LPS/O2 had more
      pronounced contractile deficiencies than similarly exposed females, but females
      tended to have long PR intervals. While both sexes demonstrated decreases in
      alpha-myosin heavy chain and connexin 43 after LPS/O2 exposure compared with
      saline/room air controls, females indicated aberrant increases in microRNA 208a,
      microRNA 208b, and desmin expression. Our study supports our hypothesis that
      early life exposure to inflammation results in sex-dependent deficits in
      cardiovascular function. NEW & NOTEWORTHY Sex-specific differences in
      cardiovascular disease are recognized, but the mechanisms and origins are not
      well understood. Adverse maternal environments can influence cardiac development
      and later cardiovascular disease. This study identifies sex-dependent differences
      in cardiac disease associated with perinatal inflammation.

PMID- 29212792
TI  - Differential effects of alcohol and its metabolite acetaldehyde on vascular
      smooth muscle cell Notch signaling and growth.
AB  - Alcohol (EtOH) consumption can variously affect cardiovascular disease. Our aim
      was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT)
      on vascular smooth muscle Notch signaling and cell growth, which are important
      for atherogenesis. Human coronary artery smooth muscle cells (HCASMCs) were
      treated with EtOH (25 mM) or ACT (10 or 25 MUM). As previously reported, EtOH
      inhibited Notch signaling and growth of HCASMCs. In contrast, ACT treatment
      stimulated HCASMC proliferation (cell counts) and increased proliferating cell
      nuclear antigen expression, concomitant with stimulation of Notch signaling, as
      determined by increased Notch receptor (N1 and N3) and target gene (Hairy-related
      transcription factor 1-3) mRNA levels. Interaction of the ligand with the Notch
      receptor initiates proteolytic cleavage by alpha- and gamma-secretase, resulting
      in the release of the active Notch intracellular domain. Neither EtOH nor ACT had
      any significant effect on alpha-secretase activity. A fluorogenic peptide
      cleavage assay demonstrated almost complete inhibition by EtOH of Delta-like
      ligand 4-stimulated gamma-secretase activity in solubilized HCASMCs (similar to
      the effect of the control inhibitor DAPT) but no effect of ACT treatment. EtOH,
      but not ACT, affected the association and distribution of the gamma-secretase
      catalytic subunit presenilin-1 with lipid rafts, as determined by dual
      fluorescent labeling and confocal microscopic visualization. In conclusion, ACT
      stimulates vascular smooth muscle cell Notch signaling and growth, effects
      opposite to those of EtOH. These differential actions on vascular smooth muscle
      cells of EtOH and its metabolite ACT may be important in mediating the ultimate
      effects of drinking on cardiovascular disease. NEW & NOTEWORTHY Acetaldehyde
      stimulates, in a Notch-dependent manner, the vascular smooth muscle cell growth
      that contributes to atherogenesis; effects opposite to those of ethanol. These
      data suggest that in addition to ethanol itself, its metabolite acetaldehyde may
      also mediate some of the effects of alcohol consumption on vascular cells and,
      thus, cardiovascular health.

PMID- 29212793
TI  - PACAP-(6-38) or kynurenate microinjections in the RVLM prevent the development of
      sympathetic long-term facilitation after acute intermittent hypoxia.
AB  - Intermittent hypoxia causes a persistent increase in sympathetic activity that
      progresses to hypertension in chronic conditions such as obstructive sleep apnea.
      Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory
      neurotransmitter that causes long-lasting sympathetic excitation. We aimed to
      determine if intermittent activation of the rostral ventrolateral medulla (RVLM)
      causes PACAP-mediated elevation of sympathetic nerve activity, termed sympathetic
      long-term facilitation (sLTF). The role of PACAP in mediating sLTF in response to
      intermittent activation of the RVLM was investigated in urethane-anaesthetized
      and artificially ventilated rats ( n = 65, Sprague-Dawley). Bilateral RVLM
      microinjections of the PACAP type 1 receptor/vasoactive intestinal polypeptide
      receptor type 2 receptor antagonist PACAP-(6-38) [ n = 6, change (Delta): -16.4
      +/- 6.5%) or an ionotropic glutamate antagonist, kynurenate ( n = 6, Delta:-7.2
      +/- 2.3%), blocked the development of acute intermittent hypoxia-induced sLTF ( n
      = 6, Delta: 49.2 +/- 14.2%). Intermittent RVLM microinjections of glutamate
      caused sLTF ( n = 5, Delta: 56.9 +/- 14.7%) that was abolished by PACAP-(6-38)
      pretreatment ( n = 5, Delta:-1.2 +/- 4.7%). Conversely, intermittent
      microinjections of PACAP in the RVLM did not elicit sLTF. Intermittent bilateral
      disinhibition of the RVLM by microinjection of gamma-aminobutyric acid in the
      caudal ventrolateral medulla did not elicit sLTF. Direct activation of RVLM
      neurons is crucial for the development of sLTF. PACAP and glutamate act
      synergistically in the RVLM, with both being necessary for the sLTF response. We
      found that activation of glutamate but not PACAP receptors is necessary and
      sufficient to generate sLTF, even in the absence of intermittent hypoxia. Our
      results demonstrate that PACAP within the RVLM may contribute to the development
      of obstructive sleep apnea -induced hypertension. NEW & NOTEWORTHY
      Pharmacological blockade of either pituitary adenylate cyclase-activating
      polypeptide (PACAP) or ionotropic glutamate receptors in the rostral
      ventrolateral medulla prevents development of sympathetic long-term facilitation.
      PACAP receptor inhibition prevents the occurrence of hypoxia-induced peripheral
      chemoreflex sensitization. Thus, PACAP receptors may be a potential therapeutic
      target serving to reduce heightened sympathetic tone and hypersensitized
      cardiovascular reflexes.

PMID- 29212794
TI  - Ferroptosis: beating on death's door.

PMID- 29212796
TI  - QTL mapping for microtuber dormancy and GA3 content in a diploid potato
      population.
AB  - The genetic control of dormancy is poorly understood in most plant species, but
      dormancy is a prominent feature for the potato industry. We used the microtuber
      system, in which tubers were produced in vitro and stored at 20 degrees C, to
      perform quantitative trait locus (QTL) analysis for dormancy and gibberellic acid
      (GA3) content in an F1 population consisting of 178 genotypes derived from an
      interspecific cross between Solanum chacoense acc. PI 320285 (long dormancy) and
      Solanum phureja acc. DM1-3 516 R44 (short dormancy). In this analysis, 163
      markers were used to construct a genetic map with a total length of 591.8 cM.
      Through QTL analysis, we identified 22 markers closely linked to the timing of
      dormancy release and GA3 content. The male parent alleles were closely related
      with long dormancy, with the most significant effect on chromosome I, which
      accounted for 9.4% of phenotypic variation. The dormancy and GA3 QTLs localized
      to the same position in the genome, confirming that same genomic region controls
      GA3 content at different developmental stages or in dormant and sprouting tubers.
      The identified QTLs may be useful for future breeding strategies and studies of
      dormancy in potato.

PMID- 29212795
TI  - Degradation pathway of plant complex-type N-glycans: identification and
      characterization of a key alpha1,3-fucosidase from glycoside hydrolase family 29.
AB  - Plant complex-type N-glycans are characterized by the presence of alpha1,3-linked
      fucose towards the proximal N-acetylglucosamine residue and beta1,2-linked xylose
      towards the beta-mannose residue. These glycans are ultimately degraded by the
      activity of several glycoside hydrolases. However, the degradation pathway of
      plant complex-type N-glycans has not been entirely elucidated because the gene
      encoding alpha1,3-fucosidase, a glycoside hydrolase acting on plant complex-type
      N-glycans, has not yet been identified, and its substrate specificity remains to
      be determined. In the present study, we found that AtFUC1 (an Arabidopsis GH29
      alpha-fucosidase) is an alpha1,3-fucosidase acting on plant complex-type N
      glycans. This fucosidase has been known to act on alpha1,4-fucoside linkage in
      the Lewis A epitope of plant complex-type N-glycans. We found that this glycoside
      hydrolase specifically acted on GlcNAcbeta1-4(Fucalpha1-3)GlcNAc, a degradation
      product of plant complex-type N-glycans, by sequential actions of vacuolar alpha
      mannosidase, beta1,2-xylosidase, and endo-beta-mannosidase. The AtFUC1-deficient
      mutant showed no distinct phenotypic plant growth features; however, it
      accumulated GlcNAcbeta1-4(Fucalpha1-3)GlcNAc, a substrate of AtFUC1. These
      results showed that AtFUC1 is an alpha1,3-fucosidase acting on plant complex-type
      N-glycans and elucidated the degradation pathway of plant complex-type N-glycans.

PMID- 29212797
TI  - In vitro and in vivo differentiation of induced pluripotent stem cells generated
      from urine-derived cells into cardiomyocytes.
AB  - Generation of human cardiomyocytes from cells derived from various sources,
      including skin biopsy, has been made possible by breakthrough advances in stem
      cell research. However, it is attractive to build up a negligibly invasive way to
      create induced pluripotent stem (iPS) cells. In this study, we created iPS cells
      from human urine-derived epithelial cells by gene transduction using lentiviral
      vectors in a totally noninvasive manner. Then, we induced the differentiation of
      iPS cells into functional cardiomyocytes both in vitro and in vivo Action
      potentials were recorded in putative cardiomyocytes and spontaneous beating cells
      were observed. Our results offered an alternative method to generate
      cardiomyocytes in a totally noninvasive manner from an easily accessible source.
      The availability of urine and its potent reprogramming characteristics will
      provide opportunities for the use of cells with specific genotypes to study the
      pathogenesis and molecular mechanisms of disease in vitro.

PMID- 29212798
TI  - The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of
      beta-catenin, a GSK3 substrate, in human glioblastoma cells.
AB  - Lithium salt is a classic glycogen synthase kinase 3 (GSK3) inhibitor. Beryllium
      is a structurally related inhibitor that is more potent but relatively
      uncharacterized. This study examined the effects of these inhibitors on the
      phosphorylation of endogenous GSK3 substrates. In NIH-3T3 cells, both salts
      caused a decrease in phosphorylated glycogen synthase, as expected. GSK3
      inhibitors produce enhanced phosphorylation of Ser9 of GSK3beta via a positive
      feedback mechanism, and both salts elicited this enhancement. Another GSK3
      substrate is beta-catenin, which has a central role in Wnt signaling. In A172
      human glioblastoma cells, lithium treatment caused a surprising increase in
      phospho-Ser33/Ser37-beta-catenin, which was quantified using an antibody-coupled
      capillary electrophoresis method. The beta-catenin hyperphosphorylation was
      unaffected by p53 RNAi knockdown, indicating that p53 is not involved in the
      mechanism of this response. Lithium caused a decrease in the abundance of axin, a
      component of the beta-catenin destruction complex that has a role in coordinating
      beta-catenin ubiquitination and protein turnover. The axin and phospho-beta
      catenin results were reproduced in U251 and U87MG glioblastoma cell lines. These
      observations run contrary to the conventional view of the canonical Wnt signaling
      pathway, in which a GSK3 inhibitor would be expected to decrease, not increase,
      phospho-beta-catenin levels.This article has an associated First Person interview
      with the first author of the paper.

PMID- 29212799
TI  - LIF-activated Jak signaling determines Esrrb expression during late-stage
      reprogramming.
AB  - The regulatory process of naive-state induced pluripotent stem cell (iPSC)
      generation is not well understood. Leukemia inhibitory factor (LIF)-activated
      Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is
      the master regulator for naive-state pluripotency achievement and maintenance.
      The estrogen-related receptor beta (Esrrb) serves as a naive-state marker gene
      regulating self-renewal of embryonic stem cells (ESCs). However, the
      interconnection between Esrrb and LIF signaling for pluripotency establishment in
      reprogramming is unclear. We screened the marker genes critical for complete
      reprogramming during mouse iPSC generation, and identified genes including Esrrb
      that are responsive to LIF/Jak pathway signaling. Overexpression of Esrrb resumes
      the reprogramming halted by inhibition of Jak activity in partially reprogrammed
      cells (pre-iPSCs), and leads to the generation of pluripotent iPSCs. We further
      show that neither overexpression of Nanog nor stimulation of Wnt signaling, two
      upstream regulators of Esrrb in ESCs, stimulates the expression of Esrrb in
      reprogramming when LIF or Jak activity is blocked. Our study demonstrates that
      Esrrb is a specific reprogramming factor regulated downstream of the LIF/Jak
      signaling pathway. These results shed new light on the regulatory role of LIF
      pathway on complete pluripotency establishment during iPSC generation.

PMID- 29212800
TI  - Extracellular retention of PDGF-B directs vascular remodeling in mouse hypoxia
      induced pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a lethal condition, and current vasodilator
      therapy has limited effect. Antiproliferative strategies targeting platelet
      derived growth factor (PDGF) receptors, such as imatinib, have generated
      promising results in animal studies. Imatinib is, however, a nonspecific tyrosine
      kinase inhibitor and has in clinical studies caused unacceptable adverse events.
      Further studies are needed on the role of PDGF signaling in PH. Here, mice
      expressing a variant of PDGF-B with no retention motif ( Pdgfbret/ret), resulting
      in defective binding to extracellular matrix, were studied. Following 4 wk of
      hypoxia, right ventricular systolic pressure, right ventricular hypertrophy, and
      vascular remodeling were examined. Pdgfbret/ret mice did not develop PH, as
      assessed by hemodynamic parameters. Hypoxia did, however, induce vascular
      remodeling in Pdgfbret/ret mice; but unlike the situation in controls where the
      remodeling led to an increased concentric muscularization of arteries, the
      vascular remodeling in Pdgfbret/ret mice was characterized by a diffuse
      muscularization, in which cells expressing smooth muscle cell markers were found
      in the interalveolar septa detached from the normally muscularized intra-acinar
      vessels. Additionally, fewer NG2-positive perivascular cells were found in
      Pdgfbret/ret lungs, and mRNA analyses showed significantly increased levels of
      Il6 following hypoxia, a known promigratory factor for pericytes. No differences
      in proliferation were detected at 4 wk. This study emphasizes the importance of
      extracellular matrix-growth factor interactions and adds to previous knowledge of
      PDGF-B in PH pathobiology. In summary, Pdgfbret/ret mice have unaltered
      hemodynamic parameters following chronic hypoxia, possibly secondary to a
      disorganized vascular muscularization.

PMID- 29212801
TI  - Roles of high-mobility group box 1 and thrombin in murine pulmonary fibrosis and
      the therapeutic potential of thrombomodulin.
AB  - Cross talk between inflammation and coagulation plays important roles in acute or
      subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage.
      Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1),
      and thrombin and may be effective for this condition. This study investigated the
      roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary
      fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM).
      Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal
      instillation of bleomycin. We first assessed HMGB1, thrombin, transforming growth
      factor (TGF)-beta1, and alpha-smooth muscle actin (SMA) levels in bronchoalveolar
      lavage fluid and lung tissue sections over time. Expression of HMGB1 and thrombin
      was elevated before that of TGF-beta1 and alpha-SMA and remained high during the
      fibrotic phase after bleomycin instillation. We next examined whether in vitro
      stimulation with HMGB1 and thrombin induced expression of TGF-beta1 and alpha-SMA
      in cultured alveolar macrophages and lung fibroblasts, respectively, by
      performing quantitative PCR, enzyme-linked immunosorbent assay, Western blot, and
      immunofluorescence analyses. HMGB1 and thrombin stimulation induced TGF-beta1
      production by alveolar macrophages, and thrombin stimulation also induced alpha
      SMA expression in lung fibroblasts. Finally, we evaluated the effect of rhTM on
      bleomycin-induced pulmonary fibrosis. Compared with the vehicle control, both
      early and late-phase administration of rhTM suppressed the fibrotic process. Our
      results suggest that HMGB1 and thrombin were involved in the pathophysiology of
      pulmonary fibrosis via production of profibrotic proteins and that rhTM
      attenuated bleomycin-induced pulmonary fibrosis. rhTM may be a therapeutic option
      for acute or subacute pulmonary fibrosis.

PMID- 29212802
TI  - Transcriptional survey of alveolar macrophages in a murine model of chronic
      granulomatous inflammation reveals common themes with human sarcoidosis.
AB  - Mohan A, Malur A, McPeek M, Barna BP, Schnapp LM, Thomassen MJ, Gharib SA.
      Transcriptional survey of alveolar macrophages in a murine model of chronic
      granulomatous inflammation reveals common themes with human sarcoidosis. Am J
      Physiol Lung Cell Mol Physiol 314: L617-L625, 2018. First published December 6,
      2017; doi: 10.1152/ajplung.00289.2017 . To advance our understanding of the
      pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)
      based murine model that shows marked histological and inflammatory signal
      similarities to this disease. In this study, we compared the alveolar macrophage
      transcriptional signatures of our animal model with human sarcoidosis to identify
      overlapping molecular programs. Whole genome microarrays were used to assess gene
      expression of alveolar macrophages in six MWCNT-exposed and six control animals.
      The results were compared with the transcriptional profiles of alveolar immune
      cells in 15 sarcoidosis patients and 12 healthy humans. Rigorous statistical
      methods were used to identify differentially expressed genes. To better elucidate
      activated pathways, integrated network and gene set enrichment analysis (GSEA)
      was performed. We identified over 1,000 differentially expressed between control
      and MWCNT mice. Gene ontology functional analysis showed overrepresentation of
      processes primarily involved in immunity and inflammation in MCWNT mice. Applying
      GSEA to both mouse and human samples revealed upregulation of 92 gene sets in
      MWCNT mice and 142 gene sets in sarcoidosis patients. Commonly activated pathways
      in both MWCNT mice and sarcoidosis included adaptive immunity, T-cell signaling,
      IL-12/IL-17 signaling, and oxidative phosphorylation. Differences in gene set
      enrichment between MWCNT mice and sarcoidosis patients were also observed. We
      applied network analysis to differentially expressed genes common between the
      MWCNT model and sarcoidosis to identify key drivers of disease. In conclusion, an
      integrated network and transcriptomics approach revealed substantial functional
      similarities between a murine model and human sarcoidosis particularly with
      respect to activation of immune-specific pathways.

PMID- 29212803
TI  - Elastase alters contractility and promotes an inflammatory synthetic phenotype in
      airway smooth muscle tissues.
AB  - Neutrophil elastase is secreted by inflammatory cells during airway inflammation
      and can elicit airway hyperreactivity in vivo. Elastase can degrade multiple
      components of the extracellular matrix. We hypothesized that elastase might
      disrupt the connections between airway smooth muscle (ASM) cells and the
      extracellular matrix and that this might have direct effects on ASM tissue
      responsiveness and inflammation. The effect of elastase treatment on ASM
      contractility was assessed in vitro in isolated strips of canine tracheal smooth
      muscle by stimulation of tissues with cumulatively increasing concentrations of
      acetylcholine (ACh) and measurement of contractile force. Elastase treatment
      potentiated contractile responses to ACh at low concentrations but suppressed the
      maximal contractile force generated by the tissues without affecting the
      phosphorylation of myosin regulatory light chain (RLC). Elastase also promoted
      the secretion of eotaxin and the activation of Akt in ASM tissues and decreased
      expression of smooth muscle myosin heavy chain, consistent with promotion of a
      synthetic inflammatory phenotype. As the degradation of matrix proteins can alter
      integrin engagement, we evaluated the effect of elastase on the assembly and
      activation of integrin-associated adhesion junction complexes in ASM tissues.
      Elastase led to talin cleavage, reduced talin binding to vinculin, and suppressed
      activation of the adhesome proteins paxillin, focal adhesion kinase, and
      vinculin, indicating that elastase causes the disassembly of adhesion junction
      complexes and the inactivation of adhesome signaling proteins. We conclude that
      elastase promotes an inflammatory phenotype and increased sensitivity to ACh in
      ASM tissues by disrupting signaling pathways mediated by integrin-associated
      adhesion complexes.

PMID- 29212804
TI  - Myeloproliferative neoplasms: from origins to outcomes.
AB  - Substantial progress has been made in our understanding of the pathogenetic basis
      of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade
      ago heralded a new age for patient care as a consequence of improved diagnosis
      and the development of therapeutic JAK inhibitors. The more recent identification
      of mutations in calreticulin brought with it a sense of completeness, with most
      patients with myeloproliferative neoplasm now having a biological basis for their
      excessive myeloproliferation. We are also beginning to understand the processes
      that lead to acquisition of somatic mutations and the factors that influence
      subsequent clonal expansion and emergence of disease. Extended genomic profiling
      has established a multitude of additional acquired mutations, particularly
      prevalent in myelofibrosis, where their presence carries prognostic implications.
      A major goal is to integrate genetic, clinical, and laboratory features to
      identify patients who share disease biology and clinical outcome, such that
      therapies, both existing and novel, can be better targeted.

PMID- 29212805
TI  - When can we stop anticoagulation in patients with cancer-associated thrombosis?
AB  - The optimal duration of anticoagulation in patients with cancer-associated venous
      thromboembolism (VTE) is unknown. Without well-designed studies evaluating the
      efficacy, safety and cost-effectiveness of continuing anticoagulant therapy
      beyond the acute treatment period of 3 to 6 months, evidence-based
      recommendations are lacking. Consensus guidelines generally suggest continuing
      anticoagulation in patients with active cancer or receiving cancer treatment,
      with periodic reassessment of the risks and benefits. Unfortunately, with very
      little published data on the epidemiology of cancer-associated VTE beyond the
      initial 6 months, it is not possible for clinicians and patients to weigh risks
      and benefits in a quantitatively informed manner. Further research is needed to
      provide reliable and contemporary estimates on the risk of recurrent VTE off
      anticoagulation, risk of bleeding on anticoagulation, case fatality or all-cause
      mortality, and other important consequences of living with cancer-associated VTE.
      This chapter provides an overview of the published literature on real-world data
      on anticoagulant therapy use, the risks and risk factors of recurrent VTE and
      bleeding, and patient preference and values regarding long-term anticoagulation.
      It will conclude with a pragmatic, experience-informed approach for tailoring
      anticoagulant therapy in patients with cancer-associated VTE.

PMID- 29212789
TI  - Pancreatic beta-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.
AB  - The pancreatic beta-cell plays a key role in glucose homeostasis by secreting
      insulin, the only hormone capable of lowering the blood glucose concentration.
      Impaired insulin secretion results in the chronic hyperglycemia that
      characterizes type 2 diabetes (T2DM), which currently afflicts >450 million
      people worldwide. The healthy beta-cell acts as a glucose sensor matching its
      output to the circulating glucose concentration. It does so via metabolically
      induced changes in electrical activity, which culminate in an increase in the
      cytoplasmic Ca2+ concentration and initiation of Ca2+-dependent exocytosis of
      insulin-containing secretory granules. Here, we review recent advances in our
      understanding of the beta-cell transcriptome, electrical activity, and insulin
      exocytosis. We highlight salient differences between mouse and human beta-cells,
      provide models of how the different ion channels contribute to their electrical
      activity and insulin secretion, and conclude by discussing how these processes
      become perturbed in T2DM.

PMID- 29212806
TI  - Syndecan-1 promotes Wnt/beta-catenin signaling in multiple myeloma by presenting
      Wnts and R-spondins.
AB  - Multiple myeloma (MM) is characterized by the expansion of malignant plasma cells
      in the bone marrow (BM). Most MMs display aberrant Wnt/beta-catenin signaling,
      which drives proliferation; however, they lack oncogenic Wnt pathway mutations,
      suggesting activation by autocrine Wnt ligands and/or paracrine Wnts from the BM
      microenvironment. Expression of the heparan sulfate (HS) proteoglycan syndecan-1
      is a hallmark of MM. Syndecan-1 is a critical player in the complex reciprocal
      interaction between MM cells and their BM niche, mediating growth factor/cytokine
      binding and signaling by its HS chains. Here, by means of CRISPR/Cas9-mediated
      knockout and doxycycline-inducible short hairpin RNA-mediated knockdown of EXT1,
      a critical enzyme for HS polymerization, we demonstrate that the HS chains
      decorating syndecan-1 mediate aberrant Wnt pathway activation in MM. HS-deficient
      MM cells exhibited strongly decreased autocrine Wnt/beta-catenin pathway activity
      and reduced Wnt pathway-dependent proliferation. In addition, we demonstrate that
      Wnts bind to the HS side chains of syndecan-1 and that this binding contributes
      to paracrine Wnt pathway activation through the Wnt receptor Frizzled (Fzd).
      Furthermore, in an HS-dependent fashion, syndecan-1 also binds osteoblast
      produced R-spondin, which represses Fzd degradation by activation of LGR4, an R
      spondin receptor aberrantly expressed on MM cells. Costimulation with R-spondin
      and its binding to HS chains decorating syndecan-1 are indispensable for optimal
      stimulation of Wnt signaling in MM. Taken together, our results identify syndecan
      1 as a crucial component of the Wnt signalosome in MM cells, binding Wnts and R
      spondins to promote aberrant Wnt/beta-catenin signaling and cell growth, and
      suggest HS and its biosynthetic enzymes as potential targets in the treatment of
      MM.

PMID- 29212807
TI  - Independent and interactive effects of incremental heat strain, orthostatic
      stress, and mild hypohydration on cerebral perfusion.
AB  - The purpose of this study was to identify the dose-dependent effects of heat
      strain and orthostasis [via lower body negative pressure (LBNP)], with and
      without mild hypohydration, on systemic function and cerebral perfusion. Eleven
      men (means +/- SD: 27 +/- 7 y; body mass 77 +/- 6 kg), resting supine in a water
      perfused suit, underwent progressive passive heating [0.5 degrees C increments in
      core temperature (Tc; esophageal to +2.0 degrees C)] while euhydrated (EUH) or
      hypohydrated (HYPO; 1.5-2% body mass deficit). At each thermal state, mean
      cerebral artery blood velocity (MCAvmean; transcranial Doppler), partial pressure
      of end-tidal carbon dioxide ([Formula: see text]), heart rate (HR) and mean
      arterial blood pressure (MAP; photoplethysmography) were measured continuously
      during LBNP (0, -15, -30, and -45 mmHg). Four subjects became intolerant before
      +2.0 degrees C Tc, unrelated to hydration status. Without LBNP, decreases in
      [Formula: see text] accounted fully for reductions in MCAvmean across all Tc.
      With LBNP at heat tolerance (+1.5 or +2.0 degrees C), [Formula: see text]
      accounted for 69 +/- 25% of the change in MCAvmean. The HYPO condition did not
      affect MCAvmean or any cardiovascular variables during combined LBNP and passive
      heat stress (all P > 0.13). These findings indicate that hypocapnia accounted
      fully for the reduction in MCAvmean when passively heat stressed in the absence
      of LBNP and for two- thirds of the reduction when at heat tolerance combined with
      LBNP. Furthermore, when elevations in Tc are matched, mild hypohydration does not
      influence cerebrovascular or cardiovascular responses to LBNP, even when stressed
      by a combination of hyperthermia and LBNP.

PMID- 29212808
TI  - Gestational age at time of in utero lipopolysaccharide exposure influences the
      severity of inflammation-induced diaphragm weakness in lambs.
AB  - The preterm diaphragm is functionally immature compared with its term
      counterpart. In utero inflammation further exacerbates preterm diaphragm
      dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero
      inflammation-induced diaphragm dysfunction compared with term lambs. Pregnant
      ewes received intra-amniotic (IA) injections of saline or 10 mg
      lipopolysaccharide (LPS) 2 or 7 days before delivery at 121 days (preterm) or
      ~145 days (term) of gestation. Diaphragm contractile function was assessed in
      vitro. Plasma cytokines, diaphragm myosin heavy chain (MHC) isoforms, and
      oxidative stress were evaluated. Maximum diaphragm force in preterm control lambs
      was significantly lower (22%) than in term control lambs ( P < 0.001). Despite
      similar inflammatory cytokine responses to in utero LPS exposure, diaphragm
      function in preterm and term lambs was affected differentially. In term lambs,
      maximum force after a 2-day LPS exposure was significantly lower than in controls
      (by ~20%, P < 0.05). In preterm lambs, maximum forces after 2-day and 7-day LPS
      exposures were significantly lower than in controls (by ~30%, P < 0.05). Peak
      twitch force after LPS exposure was significantly lower in preterm than in
      controls, but not in term lambs. In term lambs, LPS exposure increased the
      proportion of MHC-I fibers, increased twitch contraction times, and increased
      fatigue resistance relative to controls. In preterm diaphragm, the cross
      sectional area of embryonic MHC fibers was significantly lower after 7-day versus
      2-day LPS exposures. We conclude that preterm lambs are more vulnerable to IA LPS
      induced diaphragm dysfunction than term lambs. In utero inflammation exacerbates
      diaphragm dysfunction and may increase susceptibility to postnatal respiratory
      failure.

PMID- 29212809
TI  - Animal models of preeclampsia: translational failings and why.
AB  - Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of
      both maternal and fetal morbidity and mortality. Our current understanding of the
      cause(s) of preeclampsia is far from complete, and the lack of a single reliable
      animal model that recapitulates all aspects of the disease further confounds our
      understanding. This is partially due to the heterogeneous nature of the disease,
      coupled with our evolving understanding of its etiology. Nevertheless, animal
      models are still highly relevant and useful tools that help us better understand
      the pathophysiology of specific aspects of preeclampsia. This review summarizes
      the various types and characteristics of animal models used to study
      preeclampsia, highlighting particular features of these models relevant to
      clinical translation. This review points out the strengths and limitations of
      these models to illustrate the importance of using the appropriate model
      depending on the research question.

PMID- 29212810
TI  - Heme oxygenase-1 is a potent inhibitor of placental ischemia-mediated endothelin
      1 production in cultured human glomerular endothelial cells.
AB  - Preeclampsia is a pregnancy-specific disorder of maternal hypertension and
      reduced renal hemodynamics linked to reduced endothelial function. Placental
      ischemia is thought to be the culprit of this disease, as it causes the release
      of factors like tumor necrosis factor (TNF)-alpha that induce vascular endothelin
      1 (ET-1) production. Interestingly, placental ischemia-induced hypertension in
      rats [reduced uterine perfusion pressure (RUPP) model] is abolished by ETA
      receptor blockade, suggesting a critical role for ET-1. Although it has been
      found that systemic induction of heme oxygenase (HO)-1 is associated with reduced
      ET-1 production and attenuated hypertension, it is unclear whether HO-1 directly
      modulates the increased ET-1 response to placental factors. We tested the
      hypothesis that HO-1 or its metabolites inhibit ET-1 production in human
      glomerular endothelial cells induced by serum of RUPP rats or TNF-alpha. Serum
      (5%) from RUPP hypertensive (mean arterial blood pressure 119 +/- 9 mmHg) vs.
      normotensive pregnant (NP, 101 +/- 6 mmHg, P < 0.001) rats increased ET-1
      production (RUPP 168.8 +/- 18.1 pg/ml, NP 80.3 +/- 22.7 pg/ml, P < 0.001, n =
      12/group). HO-1 induction [25 uM cobalt photoporphyrin (CoPP)] abolished RUPP
      serum-induced ET-1 production (1.6 +/- 0.8 pg/ml, P < 0.001), whereas bilirubin
      (10 uM) significantly attenuated ET-1 release (125.3 +/- 5.2 pg/ml, P = 0.005).
      Furthermore, TNF-alpha-induced ET-1 production (TNF-alpha 31.0 +/- 8.4 vs.
      untreated 7.5 +/- 0.4 pg/ml, P < 0.001) was reduced by CoPP (1.5 +/- 0.8 pg/ml, P
      < 0.001) and bilirubin (10.5 +/- 4.3 pg/ml, P < 0.001). These results suggest
      that circulating factors released during placental ischemia target the maternal
      glomerular endothelium to increase ET-1, and that pharmacological induction of HO
      1 or bilirubin could be a treatment strategy to block this prohypertensive
      pathway in preeclampsia.

PMID- 29212811
TI  - Altered expression of hepatic beta-adrenergic receptors in aging rats:
      implications for age-related metabolic dysfunction in liver.
AB  - Increased beta-adrenergic receptor (beta-AR)-mediated activation of adenylyl
      cyclase (AC) in rat liver during aging has been linked to age-related increases
      in hepatic glucose output and hepatosteatosis. In this study, we investigated the
      expression of beta-ARs, individual receptor subtypes, and G protein-coupled
      receptor (GPCR) regulatory proteins in livers from aging rats. Radioligand
      binding studies demonstrated that beta-AR density increased by greater than
      threefold in hepatocyte membranes from senescent (24-mo-old) compared with young
      adult (7-mo-old) rats and that this phenomenon was blocked by food restriction,
      which is known to retard aging processes in rodents. Competition-binding studies
      revealed a mixed population of beta1- and beta2-AR subtypes in liver membranes
      over the adult life span, with a trend for greater beta2-AR density with age.
      Expression of both beta-AR subtype mRNAs in rat liver increased with age, whereas
      beta2- but not beta1-AR protein levels declined in livers of old animals.
      Immunoreactive beta2- but not beta1-ARs were preferentially distributed in
      pericentral hepatic regions. Levels of GRK2/3 and beta-arrestin 2 proteins, which
      are involved in downregulation of agonist-activated GPCRs, including beta-ARs,
      increased during aging. Insofar as sympathetic tone increases with age, our
      findings suggest that, despite enhanced agonist-mediated downregulation of
      hepatic beta-ARs preferentially affecting the beta2-AR subtype, increased
      generation of both receptor subtypes during aging augments the pool of plasma
      membrane-bound beta-ARs coupled to AC in hepatocytes. This study thus identifies
      one or both beta-AR subtypes as possible therapeutic targets involved in aberrant
      hepatic processes of glucose and lipid metabolism during aging.

PMID- 29212813
TI  - Atrial Fibrillation: Once Again Not So Easy to Prevent.

PMID- 29212812
TI  - Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From
      the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial).
AB  - BACKGROUND: Although atrial fibrillation (AF) guidelines indicate that
      pharmacological blockade of the renin-angiotensin system may be considered for
      primary AF prevention in hypertensive patients, previous studies have yielded
      conflicting results. We sought to determine whether randomization to lisinopril
      reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a
      large clinical trial cohort with extended post-trial surveillance. METHODS AND
      RESULTS: We performed a secondary analysis of the ALLHAT (Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double
      blind, active-controlled clinical trial that enrolled hypertensive individuals
      >=55 years of age with at least one other cardiovascular risk factor.
      Participants were randomly assigned to receive amlodipine, lisinopril, or
      chlorthalidone. Individuals with elevated fasting low-density lipoprotein
      cholesterol levels were also randomized to pravastatin versus usual care. The
      primary outcome was the development of either AF or AFL as diagnosed by serial
      study ECGs or by Medicare claims data. Among 14 837 participants without
      prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5+/-3.2 years of
      follow-up. Compared with chlorthalidone, randomization to either lisinopril
      (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine
      (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not
      associated with a significant reduction in incident AF/AFL. CONCLUSIONS: Compared
      with chlorthalidone, treatment with lisinopril is not associated with a
      meaningful reduction in incident AF or AFL among older adults with a history of
      hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00000542.

PMID- 29212814
TI  - Structural basis for assembly of the CBF3 kinetochore complex.
AB  - Eukaryotic chromosomes contain a specialised region known as the centromere,
      which forms the platform for kinetochore assembly and microtubule attachment. The
      centromere is distinguished by the presence of nucleosomes containing the histone
      H3 variant, CENP-A. In budding yeast, centromere establishment begins with the
      recognition of a specific DNA sequence by the CBF3 complex. This in turn
      facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we
      describe a 3.6 A single-particle cryo-EM reconstruction of the core CBF3 complex,
      incorporating the sequence-specific DNA-binding protein Cep3 together with
      regulatory subunits Ctf13 and Skp1. This provides the first structural data on
      Ctf13, defining it as an F-box protein of the leucine-rich-repeat family, and
      demonstrates how a novel F-box-mediated interaction between Ctf13 and Skp1 is
      responsible for initial assembly of the CBF3 complex.

PMID- 29212815
TI  - Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.
AB  - Parkinson's disease predisposing LRRK2 kinase phosphorylates a group of Rab
      GTPase proteins including Rab29, within the effector-binding switch II motif.
      Previous work indicated that Rab29, located within the PARK16 locus mutated in
      Parkinson's patients, operates in a common pathway with LRRK2. Here, we show that
      Rab29 recruits LRRK2 to the trans-Golgi network and greatly stimulates its kinase
      activity. Pathogenic LRRK2 R1441G/C and Y1699C mutants that promote GTP binding
      are more readily recruited to the Golgi and activated by Rab29 than wild-type
      LRRK2. We identify conserved residues within the LRRK2 ankyrin domain that are
      required for Rab29-mediated Golgi recruitment and kinase activation. Consistent
      with these findings, knockout of Rab29 in A549 cells reduces endogenous LRRK2
      mediated phosphorylation of Rab10. We show that mutations that prevent LRRK2 from
      interacting with either Rab29 or GTP strikingly inhibit phosphorylation of a
      cluster of highly studied biomarker phosphorylation sites (Ser910, Ser935, Ser955
      and Ser973). Our data reveal that Rab29 is a master regulator of LRRK2,
      controlling its activation, localization, and potentially biomarker
      phosphorylation.

PMID- 29212817
TI  - CaSR signaling down-regulates AQP2 expression via a novel microRNA pathway in
      pendrin and NaCl cotransporter knockout mice.
AB  - High concentrations of urinary calcium counteract vasopressin action via the
      activation of the calcium-sensing receptor (CaSR) that is expressed in the
      luminal membrane of collecting duct cells, which impairs the trafficking of
      aquaporin-2 (AQP2). Pendrin/NaCl cotransporter double-knockout (dKO) mice display
      significant calcium wasting and develop severe volume depletion, despite
      increased circulating vasopressin levels. We hypothesized that the CaSR-mediated
      impairment of AQP2 expression/trafficking underlies vasopressin resistance in dKO
      mice. Compared with wild-type mice, in renal inner medulla, dKO mice had reduced
      total AQP2 sensitive to proteasome inhibitors, higher levels of AQP2-pS261,
      ubiquitinated AQP2, and p38-MAPK, an enzyme that is activated by CaSR signaling
      and known to phosphorylate AQP2 at Ser261. CaSR inhibition with the calcilytic
      NPS2143 reversed these effects, which indicates that CaSR mediates the up
      regulation of AQP2-pS261, ubiquitination, and degradation. Of note, dKO mice
      demonstrated significantly higher AQP2-targeting miRNA-137 that was reduced upon
      CaSR inhibition, supporting a critical role for CaSR in the down-regulation of
      AQP2 expression. Our data indicate that CaSR signaling reduces AQP2 abundance
      both via AQP2-targeting miRNA-137 and the p38-MAPK/AQP2
      pS261/ubiquitination/proteasomal axis. These effects may contribute to the
      reduced renal concentrating ability that has been observed in dKO mice and
      underscore a physiologic mechanism of the CaSR-dependent regulation of AQP2
      abundance via a novel microRNA pathway.-Ranieri, M., Zahedi, K., Tamma, G.,
      Centrone, M., Di Mise, A., Soleimani, M., Valenti, G. CaSR signaling down
      regulates AQP2 expression via a novel microRNA pathway in pendrin and NaCl
      cotransporter knockout mice.

PMID- 29212816
TI  - Complete suppression of Htt fibrilization and disaggregation of Htt fibrils by a
      trimeric chaperone complex.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded
      CAG trinucleotide repeat in the huntingtin gene (HTT). Molecular chaperones have
      been implicated in suppressing or delaying the aggregation of mutant Htt. Using
      in vitro and in vivo assays, we have identified a trimeric chaperone complex
      (Hsc70, Hsp110, and J-protein) that completely suppresses fibrilization of
      HttExon1Q48 The composition of this chaperone complex is variable as recruitment
      of different chaperone family members forms distinct functional complexes. The
      trimeric chaperone complex is also able to resolubilize Htt fibrils. We confirmed
      the biological significance of these findings in HD patient-derived neural cells
      and on an organismal level in Caenorhabditis elegans Among the proteins in this
      chaperone complex, the J-protein is the concentration-limiting factor. The single
      overexpression of DNAJB1 in HEK293T cells is sufficient to profoundly reduce
      HttExon1Q97 aggregation and represents a target of future therapeutic avenues for
      HD.

PMID- 29212819
TI  - Transcriptional and translational dynamics during maternal-to-zygotic transition
      in early chicken development.
AB  - Maternal-to-zygotic transition (MZT) is the critical process for the
      establishment of embryonic identity across vertebrates. During this period, the
      massive transcriptional activation, called zygotic genome activation (ZGA), is
      mediated by maternally stored factors, and maternal mRNA clearance by conserved
      zygotic microRNAs (miRNAs) occurs; however, the important transition in avian
      species was identified by morphologic perspectives only. In this study, we
      performed transcriptome analysis to examine the molecular transitions of
      intrauterine development in chickens. On the basis of coexpression analyses on
      RNA sequencing data, 2 waves of ZGA-mediated MZT were observed across the early
      embryonic stages and were associated with transcriptional and translational
      dynamics. Furthermore, definite transitions were observed according to the
      distinct developmental characteristics between cleavage and the area pellucida
      formation period in the functional analysis. Finally, epigenetic modification and
      the evolutionarily conserved miRNA expression suggest that certain MZT proceeds
      from Eyal-Giladi and Kochav stage VIII in early chicken development. We expect
      our study to provide an evolutionary link among vertebrates from the perspective
      of MZT regulation.-Hwang, Y. S., Seo, M., Bang, S., Kim, H., Han, J. Y.
      Transcriptional and translational dynamics during maternal-to-zygotic transition
      in early chicken development.

PMID- 29212818
TI  - The histone demethylase KDM5A is required for the repression of astrocytogenesis
      and regulated by the translational machinery in neural progenitor cells.
AB  - Histone demethylases are known to play important roles in the determination of
      the fate of stem cells and in cancer progression. In this study, we show that the
      lysine 4 of histone H3 (H3K4), lysine-specific demethylase 5A (KDM5A) is
      essential for the repression of astrocyte differentiation in neural progenitor
      cells (NPCs), and its expression is regulated by translational machinery.
      Knockdown of KDM5A in NPCs increased astrocytogenesis, and conversely, KDM5A
      overexpression reduced the transcriptional activity of the Gfap promoter.
      Induction of astrocytogenesis by ciliary neurotrophic factor (CNTF) or small
      interfering RNA-induced knockdown of KDM5A decreased KDM5A recruitment to the
      Gfap promoter and increased H3K4 methylation. The transcript level of Kdm5a was
      high, whereas KDM5A protein level was low in CNTF induced astrocytes. During
      astroglial differentiation, translational activity indicated by the
      phosphorylation of eukaryotic translation initiation factor (eIF)4E was
      decreased. Treatment of NPCs with the cercosporamide, a MAPK-interacting kinases
      inhibitor, reduced eIF4E phosphorylation and KDM5A protein expression, increased
      GFAP levels, and enhanced astrocytogenesis. These data suggest that KDM5A is a
      key regulator that maintains NPCs in an undifferentiated state by repressing
      astrocytogenesis and that its expression is translationally controlled during
      astrocyte differentiation. Thus, KDM5A is a promising target for the modulation
      of NPC fate.-Kong, S.-Y., Kim, W., Lee, H.-R., Kim, H.-J. The histone demethylase
      KDM5A is required for the repression of astrocytogenesis and regulated by the
      translational machinery in neural progenitor cells.

PMID- 29212820
TI  - Vision in former very low birthweight young adults with and without retinopathy
      of prematurity compared with term born controls: the NZ 1986 VLBW follow-up
      study.
AB  - OBJECTIVE: There are few data on visual outcomes in adulthood of former very low
      birthweight (VLBW; <1500 g) infants. We aimed to assess vision at 27-29 years in
      a national cohort of VLBW infants born in 1986 and assessed for retinopathy of
      prematurity (ROP) when no treatment was available, compared with term born
      controls. METHODS: The cohort and controls attended a 2-day assessment in
      Christchurch as part of a larger study. Visual assessment included glasses
      prescription measured by focimeter, logarithm of the minimum angle of resolution
      (logMAR) distance visual acuity (VA), contrast sensitivity, autorefraction,
      retinal photographs and a questionnaire on vision-related everyday activities.
      Rates of reduced VA and myopia in the VLBW cohort at 27-29 were compared with the
      results of vision testing at 7-8 years. RESULTS: 250 VLBW adults (77% those
      alive) gave study consent and 229 (45 with a history of ROP) were assessed in
      Christchurch, plus 100 term born controls. VLBW adults with ROP had reduced VA
      compared with no ROP and controls (mean logMAR score (SD); 0.003 (0.19), -0.021
      (0.16), -0.078 (0.09), P=0.001). There were no differences in myopia (>2 D)
      between the groups but high myopia (>5 D) was confined to those with ROP. VLBW
      adults with ROP drove a car less often and had higher difficulties with everyday
      activities scores due to eyesight. Between 7-8 and 27-29 years rates of reduced
      VA were stable but myopia increased. CONCLUSION: Former VLBW young adults with
      ROP have ongoing problems with vision affecting daily living and should continue
      in regular ophthalmological review. TRIAL REGISTRATION NUMBER:
      ACTRN12612000995875, Pre-results .

PMID- 29212821
TI  - Trabeculectomy bleb needling and antimetabolite administration practices in the
      UK: a glaucoma specialist national survey.
AB  - AIMS: To evaluate, describe and quantify the diversity in postoperative
      antimetabolite administration and bleb needling practices among glaucoma
      specialists performing trabeculectomy surgery within the UK and Ireland. METHODS:
      A cross-sectional online survey was distributed to all consultant glaucoma
      specialists who are on the United Kingdom and Eire Glaucoma Society (UKEGS)
      contact list. Participants were asked specific questions about their current
      practices for post-trabeculectomy antimetabolite administration followed by
      questions directly related to bleb needling procedures. RESULTS: 60 (83%) of
      UKEGS glaucoma subspecialty consultants completed the survey. 70% of respondents
      administered 5-fluorouracil (5-FU) in their clinic room while 30% used a separate
      treatment room. Doses of 5-FU varied considerably but 70% used 5 mg as standard.
      Techniques used to reduce corneal toxicity included precipitation with
      amethocaine (44%) or benoxinate (14%), saline wash (14%) and modified injection
      technique (8%). Topical antibiotics and/or betadine were used to prevent
      infection following 5-FU injection in just over 50%. Bleb needling was
      exclusively performed in operating theatre by 56% of respondents and solely at
      the slit lamp in the clinic room by 12%. A further 30% used a combination of both
      theatre and outpatient clinic rooms. Anti-metabolites used were 5-FU (72%) and
      mitomycin C (22%) with 12% using either of the two substances. CONCLUSIONS: There
      is a significantly wide variety of current practices for antimetabolite
      administration and bleb needling within the UK and Ireland. This may be
      influenced by a glaucoma surgeon's specific experience and audit results as well
      as particular clinical set-up, availability of antimetabolite and clinic room
      space.

PMID- 29212822
TI  - Effect of Probiotics on Pharmacokinetics of Orally Administered Acetaminophen in
      Mice.
AB  - Orally administered probiotics change gut microbiota composition and enzyme
      activities. Thus, coadministration of probiotics with drugs may lead to changes
      in the pharmacokinetic parameters of the drugs. In this study, we investigated
      the pharmacokinetics of acetaminophen in mice treated with probiotics. Oral
      administration of probiotics changed the gut microbiota composition in the mice.
      Of these probiotics, Lactobacillus reuteri K8 increased the numbers of
      clostridia, bifidobacteria, and enterococci, and Lactobacillus rhamnosus K9
      decreased the number of bifidobacteria, determined by culturing in selective
      media. Next, we performed a pharmacokinetic study of acetaminophen in mice orally
      treated with K8 and K9 for 3 days. Treatment with K8 reduced the area under the
      curve (AUC) of orally administered acetaminophen to 68.4% compared with normal
      control mice, whereas K9 did not affect the AUC of acetaminophen. Oral
      administration to mice of K8, which degraded acetaminophen, increased the
      degradation of acetaminophen by gut microbiota, whereas K9 treatment did not
      affect it. Treatment with K8 increased the number of L. reuteri adhered in the
      upper small intestine, whereas the number of L. rhamnosus was not affected by
      treatment with K8 or K9. K8 increased the number of cyanobacteria, whereas K9
      increased the number of deferribacteres. These results suggest that the intake of
      probiotics may make the absorption of orally administered drugs fluctuate through
      the disturbance of gut microbiota-mediated drug metabolism and that the
      subsequent impact on microbiota metabolism could result in altered systemic
      concentrations of the intact drug.

PMID- 29212823
TI  - Quantitative Expression of Hepatobiliary Transporters and Functional Uptake of
      Substrates in Hepatic Two-Dimensional Sandwich Cultures: A Comparative Evaluation
      of Upcyte and Primary Human Hepatocytes.
AB  - Deficient functional expression of drug transporters incapacitates most hepatic
      cell lines as a reliable tool for evaluating transporter-mediated drug-drug
      interactions. Recently, genetically modified cells (referred to as upcyte
      hepatocytes) have emerged as an expandable, noncancerous source of human hepatic
      cells. Herein, we quantified mRNA and protein levels of key hepatobiliary
      transporters and we assessed associated uptake activity in short- and long-term
      cultures of upcyte human hepatocytes (UHH) in comparison to cryopreserved primary
      human hepatocytes (cPHH). Expression of canalicular efflux pumps, such as
      MRD1/ABCB1, MATE1/SLC47A1, and MRP2/ABCC2, was relatively well preserved in UHH.
      By contrast, long-term cultivation of UHH in a two-dimensional sandwich
      configuration [sandwich-cultured upcyte human hepatocytes (SCUHH)] was required
      to upregulate organic anion-transporting polypeptide OATP1B1/SLCO1B1,
      OATP2B1/SLCO2B1, NTCP/SLC10A1, and OCT1/SLC22A1 mRNA expression, which correlated
      well with respective protein abundances. However, mRNA and protein levels of
      sinusoidal solute carrier transporters, except for NTCP and OATP2B1, remained low
      in SCUHH compared to sandwich-cultured cPHH. OCT1- and NTCP-mediated uptake of N
      methyl-4-phenylpyridinium acetate and taurocholate was demonstrated in both
      hepatic models, whereas active uptake of OATP1B1/1B3-selective marker substrates,
      paralleled by markedly reduced SLCO1B1/1B3 expression, were not detectable in
      SCUHH. Uptake studies under Na+-depletion and excess of taurocholate confirmed
      the presence of functional NTCP protein and indicated that NTCP, apart from
      OATP2B1, contributed substantially to the overall hepatic uptake of rosuvastatin
      in SCUHH. In conclusion, our data suggest that SCUHH, despite their limitation
      for evaluating OATP1B1/1B3-mediated transport processes, retain NTCP, OATP2B1,
      and OCT1 transport activities and thus may be considered as a tool for
      elucidating compensatory uptake pathways for OATP1B1/1B3 substrates.

PMID- 29212824
TI  - Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin
      Beneficially Affects Insulin Sensitivity in Humans.
AB  - OBJECTIVE: Gut microbiota represent a potential novel target for future
      prediabetes and type 2 diabetes therapies. In that respect, niacin has been shown
      to beneficially affect the host-microbiome interaction in rodent models. RESEARCH
      DESIGN AND METHODS: We characterized more than 500 human subjects with different
      metabolic phenotypes regarding their niacin (nicotinic acid [NA] and nicotinamide
      [NAM]) status and their gut microbiome. In addition, NA and NAM delayed-release
      microcapsules were engineered and examined in vitro and in vivo in two human
      intervention studies (bioavailability study and proof-of-concept/safety study).
      RESULTS: We found a reduced alpha-diversity and Bacteroidetes abundance in the
      microbiome of obese human subjects associated with a low dietary niacin intake.
      We therefore developed delayed-release microcapsules targeting the ileocolonic
      region to deliver increasing amounts of NA and NAM to the microbiome while
      preventing systemic resorption to avoid negative side effects (e.g., facial
      flushing). In vitro studies on these delayed-release microcapsules revealed
      stable conditions at pH 1.4, 4.5, and 6.8, followed by release of the compounds
      at pH 7.4, simulating the ileocolonic region. In humans in vivo, gut-targeted
      delayed-release NA but not NAM produced a significant increase in the abundance
      of Bacteroidetes. In the absence of systemic side effects, these favorable
      microbiome changes induced by microencapsulated delayed-release NA were
      associated with an improvement of biomarkers for systemic insulin sensitivity and
      metabolic inflammation. CONCLUSION: Targeted microbiome intervention by delayed
      release NA might represent a future therapeutic option for prediabetes and type 2
      diabetes.

PMID- 29212826
TI  - Diet in multiple sclerosis: Science takes a seat at the table.

PMID- 29212825
TI  - Intensive Blood Pressure Lowering in Patients With and Patients Without Type 2
      Diabetes: A Pooled Analysis From Two Randomized Trials.
AB  - OBJECTIVE: The Action to Control Cardiovascular Risk in Diabetes Blood Pressure
      (ACCORD-BP) study did not find a significant beneficial effect of intensive
      systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive
      patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure
      Intervention Trial (SPRINT) did find a significant beneficial effect in patients
      without T2DM. The objective of this analysis was to assess the effect of both
      T2DM and baseline cardiovascular disease risk on the treatment effect of
      intensive blood pressure lowering. RESEARCH DESIGN AND METHODS: The individual
      patient data from the ACCORD-BP and SPRINT studies were pooled and follow-up
      durations harmonized. Both studies randomized hypertensive patients to an SBP
      target of <120 mmHg or a target of <140 mmHg. The composite primary end point
      consisted of unstable angina, myocardial infarction, acute heart failure, stroke,
      and cardiovascular death. The interaction between intensive blood pressure
      lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox
      proportional hazards models. RESULTS: The cohort consisted of 14,094 patients
      with mean age 66 +/- 8.9 years and mean baseline SBP 139.5 +/- 15.6 mmHg; 33.6%
      had T2DM. The hazard ratio for the primary composite end point was 0.82 (95% CI
      0.73-0.93), P = 0.0017. The interaction between intensive blood pressure lowering
      and T2DM was nonsignificant (P = 0.13). The 10-year cardiovascular risk was
      higher in primary prevention patients with T2DM, but risk did not interact with
      the treatment effect (P = 0.84). CONCLUSIONS: Intensive blood pressure lowering
      may have a similar favorable effect and appears to decrease cardiovascular events
      in both patients with and patients without T2DM.

PMID- 29212827
TI  - Diet quality is associated with disability and symptom severity in multiple
      sclerosis.
AB  - OBJECTIVE: To assess the association between diet quality and intake of specific
      foods with disability and symptom severity in people with multiple sclerosis
      (MS). METHODS: In 2015, participants in the North American Research Committee on
      MS (NARCOMS) Registry completed a dietary screener questionnaire that estimates
      intake of fruits, vegetables and legumes, whole grains, added sugars, and
      red/processed meats. We constructed an overall diet quality score for each
      individual based on these food groups; higher scores denoted a healthier diet. We
      assessed the association between diet quality and disability status as measured
      using Patient-Determined Disease Steps (PDDS) and symptom severity using
      proportional odds models, adjusting for age, sex, income, body mass index,
      smoking status, and disease duration. We assessed whether a composite healthy
      lifestyle measure, a healthier diet, healthy weight (body mass index <25),
      routine physical activity, and abstinence from smoking was associated with
      symptom severity. RESULTS: Of the 7,639 (68%) responders, 6,989 reported
      physician-diagnosed MS and provided dietary information. Participants with diet
      quality scores in the highest quintile had lower levels of disability (PDDS;
      proportional odds ratio [OR] for Q5 vs Q1 0.80; 95% confidence interval [CI] 0.69
      0.93) and lower depression scores (proportional OR for Q5 vs Q1 0.82; 95% CI 0.70
      0.97). Individuals reporting a composite healthy lifestyle had lower odds of
      reporting severe fatigue (0.69; 95% CI 0.59-0.81), depression (0.53; 95% CI 0.43
      0.66), pain (0.56; 95% CI 0.48-0.67), or cognitive impairment (0.67; 95% CI 0.55
      0.79). CONCLUSIONS: Our large cross-sectional survey suggests a healthy diet and
      a composite healthy lifestyle are associated with lesser disability and symptom
      burden in MS.

PMID- 29212828
TI  - Detecting anxiety in individuals with Parkinson disease: A systematic review.
AB  - OBJECTIVE: To examine diagnostic accuracy of anxiety detection tools compared
      with a gold standard in outpatient settings among adults with Parkinson disease
      (PD). METHODS: A systematic review was conducted. MEDLINE, EMABASE, PsycINFO, and
      Cochrane Database of Systematic Reviews were searched to April 7, 2017.
      Prevalence of anxiety and diagnostic accuracy measures including sensitivity,
      specificity, and likelihood ratios were gathered. Pooled prevalence of anxiety
      was calculated using Mantel-Haenszel-weighted DerSimonian and Laird models.
      RESULTS: A total of 6,300 citations were reviewed with 6 full-text articles
      included for synthesis. Tools included within this study were the Beck Anxiety
      Inventory, Geriatric Anxiety Inventory (GAI), Hamilton Anxiety Rating Scale,
      Hospital Anxiety and Depression Scale-Anxiety, Parkinson's Anxiety Scale (PAS),
      and Mini-Social Phobia Inventory. Anxiety diagnoses made included generalized
      anxiety disorder, social phobia, and any anxiety type. Pooled prevalence of
      anxiety was 30.1% (95% confidence interval 26.1%-34.0%). The GAI had the best
      reported sensitivity of 0.86 and specificity of 0.88. The observer-rated PAS had
      a sensitivity of 0.71 and the highest specificity of 0.91. CONCLUSIONS: While
      there are 6 tools validated for anxiety screening in PD populations, most tools
      are only validated in single studies. The GAI is brief and easy to use, with a
      good balance of sensitivity and specificity. The PAS was specifically developed
      for PD, is brief, and has self-/observer-rated scales, but with lower
      sensitivity. Health care practitioners involved in PD care need to be aware of
      available validated tools and choose one that fits their practice.

PMID- 29212829
TI  - PML in a person with multiple sclerosis: Is teriflunomide the felon?

PMID- 29212830
TI  - Multicenter evaluation of neurofilaments in early symptom onset amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: To examine neurofilament (Nf) concentrations according to symptom
      onset and clinical diagnostic certainty categories of amyotrophic lateral
      sclerosis (ALS). METHODS: We measured Nf light chain (NfL) and phosphorylated Nf
      heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first
      symptom onset <=6 months (n = 54) or >6 months (n = 135) from sampling, and
      patients with other neurologic diseases, differential diagnoses of a motor neuron
      disease (MND mimics), and other MND variants to determine the diagnostic accuracy
      in patients with ALS with early symptom onset. Samples were received multicentric
      and analyzed by ELISA and Simoa platform and related to other clinical measures.
      RESULTS: NfL and pNfH in CSF and NfL in serum were increased in early and later
      symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated
      patients with ALS with early symptom onset from those with other neurologic
      diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%)
      and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not vary between
      clinical diagnostic categories of ALS in the early symptomatic phase group.
      Baseline NfL and pNfH levels were not significantly different in patients with
      ALS with clinical progression to definite or probable ALS at follow-up.
      CONCLUSION: The measurement of Nf has potential to enhance diagnostic accuracy of
      ALS in those presenting soon after symptom onset, and is measurable across
      multiple centers. CLASSIFICATION OF EVIDENCE: This study provides Class II
      evidence that CSF and serum Nf concentrations discriminate ALS with early symptom
      onset from other neurologic diseases.

PMID- 29212832
TI  - Adenosine A2A Receptor Agonist, 2-p-(2-Carboxyethyl)phenethylamino-5'-N
      ethylcarboxamidoadenosine Hydrochloride Hydrate, Inhibits Inflammation and
      Increases Fibroblast Growth Factor-2 Tissue Expression in Carrageenan-Induced Rat
      Paw Edema.
AB  - Adenosine is the final product of ATP metabolism, mainly derived from the action
      of 5'-nucleotidase cleavage of AMP. Cellular production of adenosine is greatly
      enhanced in inflamed tissues, ischemic tissues, and under hypoxia, where ATP is
      released from damaged cells. Much evidence has been accumulated on adenosine anti
      inflammatory effects mediated through A2A receptor activation; A2A adenosine
      receptor has also been shown to play a role in matrix deposition and wound
      healing in a damaged tissue, contributing to dermal tissue protection and repair.
      Fibroblast growth factor-2 (FGF-2) is a powerful mitogen for fibroblast; it is
      expressed by several inflammatory cell types and plays a pivotal role in
      angiogenesis, wound healing, gastric ulcer protection. Human recombinant FGF-2
      has been shown to have anti-inflammatory effects. The purpose of the present work
      was to investigate on the anti-inflammatory effect of systemic administration of
      the adenosine A2A agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N
      ethylcarboxamidoadenosine hydrochloride hydrate (CGS21680) in the rat model of
      carrageenan-induced paw edema. We found that CGS21680 inhibits inflammation
      induced by carrageenan injection into the rat paw, and this effect is associated
      to the local reduction of cytokine levels and dermal increase of FGF-2
      expression. Our results suggest that FGF-2 might be involved in the anti
      inflammatory and tissue protective effect due to A2A receptor activation.

PMID- 29212831
TI  - Impaired Pulmonary Arterial Vasoconstriction and Nitric Oxide-Mediated Relaxation
      Underlie Severe Pulmonary Hypertension in the Sugen-Hypoxia Rat Model.
AB  - Pulmonary vasoreactivity could determine the responsiveness to vasodilators and,
      in turn, the prognosis of pulmonary hypertension (PH). We hypothesized that
      pulmonary vasoreactivity is impaired, and we examined the underlying mechanisms
      in the Sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were
      injected with Sugen (20 mg/kg s.c.) and exposed to hypoxia (9% O2) for 3 weeks,
      followed by 4 weeks in normoxia (Su/Hx), or treated with Sugen alone (Su) or
      hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was
      assessed for right ventricular hypertrophy (Fulton's index); the pulmonary
      artery, aorta, and mesenteric arteries were isolated for vascular function
      studies; and contractile markers were measured in pulmonary arteries using
      quantitative polymerase chain reaction (PCR). Other rats were used for
      morphometric analysis of pulmonary vascular remodeling. Right ventricular
      systolic pressure and Fulton's index were higher in Su/Hx versus Su, Hx, and Nx
      rats. Pulmonary vascular remodeling was more prominent in Su/Hx versus Nx rats.
      In pulmonary artery rings, contraction to high KCl (96 mM) was less in Su/Hx
      versus Nx and Su, and phenylephrine-induced contraction was reduced in Su/Hx
      versus Nx, Hx, and Su. Acetylcholine (ACh)-induced relaxation was less in Su/Hx
      versus Nx and Hx, suggesting reduced endothelium-dependent vasodilation. ACh
      relaxation was inhibited by nitric oxide synthase (NOS) and guanylate cyclase
      blockade in all groups, suggesting a role of the NO-cGMP pathway. Nitrate/nitrite
      production in response to ACh was less in Su/Hx versus Nx, supporting reduced
      endothelial NO production. Sodium nitroprusside (10-8 M) caused less relaxation
      in Su/Hx versus Nx, Hx, and Su, suggesting a decreased responsiveness of vascular
      smooth muscle (VSM) to vasodilators. Neither contraction nor relaxation differed
      in the aorta or mesenteric arteries of all groups. PCR analysis showed decreased
      expression of contractile markers in pulmonary artery of Su/Hx versus Nx. The
      reduced responsiveness to vasoconstrictors and NO-mediated vasodilation in the
      pulmonary, but not systemic, vessels may be an underlying mechanism of severe PH
      in Su/Hx rats and appears to involve attenuation of the NO relaxation pathway and
      a switch of pulmonary VSM cells to a synthetic less reactive phenotype.

PMID- 29212833
TI  - Personalized cancer therapy-leveraging a knowledge base for clinical decision
      making.
AB  - Next-generation sequencing (NGS), also known as massively parallel sequencing, is
      rapidly being incorporated into oncology practice. Interpretation of genomic
      reports and selecting treatments based on the tumor's genomic analysis becomes
      more and more complicated for the treating oncologist because of the use of
      larger panels covering dozens to hundreds of genes and the amount of rapidly
      emerging clinical/translational data. To help guide personalized treatments in
      oncology, The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized
      Cancer Therapy (IPCT) at MD Anderson Cancer Center has developed a knowledge
      base, available at https://personalizedcancertherapy.org or
      https://pct.mdanderson.org (PCT). This knowledge base provides information on the
      function of common genomic alterations and their therapeutic implications. Here,
      we describe how such genomic information can be used by health-care providers to
      identify genomically matched therapies.

PMID- 29212834
TI  - Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      worldwide, with increasing prevalence, in particular in the elderly. COPD is
      characterised by abnormal tissue repair resulting in (small) airways disease and
      emphysema. There is accumulating evidence that ageing hallmarks are prominent
      features of COPD. These ageing hallmarks have been described in different subsets
      of COPD patients, in different lung compartments and also in a variety of cell
      types, and thus might contribute to different COPD phenotypes. A better
      understanding of the main differences and similarities between normal lung ageing
      and the pathology of COPD may improve our understanding of the mechanisms driving
      COPD pathology, in particular in those patients that develop the most severe form
      of COPD at a relatively young age, i.e. severe early-onset COPD patients.In this
      review, after introducing the main concepts of lung ageing and COPD pathology, we
      focus on the role of (abnormal) ageing in lung remodelling and repair in COPD. We
      discuss the current evidence for the involvement of ageing hallmarks in these
      pathological features of COPD. We also highlight potential novel treatment
      strategies and opportunities for future research based on our current knowledge
      of abnormal lung ageing in COPD.

PMID- 29212835
TI  - The air of Europe: where are we going?
AB  - Air pollution constitutes one of the main threats to public health in Europe.
      Significant impacts on the health of Europeans in terms of morbidity and
      mortality have been observed, even in cases of low exposure and where pollutant
      levels are within limits set by the European Union (EU). The respiratory system
      is a primary target of the harmful effects of key air pollutants. Emissions of
      many air pollutants have decreased substantially over the past decades in Europe,
      resulting in diminished concentrations and improved air quality. However, in
      several European cities concentrations still exceed EU reference values and, more
      often, the stricter World Health Organization air quality guidelines for all
      regulated air pollutants (particles with 50% cut-off aerodynamic diameters of 10
      and 2.5 um, nitrogen dioxide (NO2), benzo[a]pyrene and ozone (O3)) except sulfur
      dioxide. In addition, current trends indicate that in the absence of substantial
      changes, particulate matter, NO2 and O3 will still exceed limits in 2020.
      Additional efforts must be made to comply with current standards and guidelines.
      These should include a more accurate and detailed monitoring of air pollutants,
      reduction of emissions and individual behaviour changes.

PMID- 29212836
TI  - Inhaler technique: does age matter? A systematic review.
AB  - Poor inhaler technique and inferior asthma outcomes are evident in older adults.
      Reviews comparing metered dose inhaler (MDI) and dry powder inhaler (DPI)
      techniques across older adults and younger cohorts are scarce. This systematic
      review aimed to determine whether differences exist between such cohorts with
      regards to the number and type of MDI and DPI errors made. A systematic
      literature search was conducted in Embase, Medline and PubMed from July 1 to
      December 31, 2016. Studies were selected in accordance with preset inclusion
      criteria, relevant data were extracted, and quality was assessed with validated
      checklists. 14 studies were identified. Evidence suggests a negative correlation
      between advancing age and correct technique across MDI and varying DPI devices
      when examined collectively. Differences appear to exist between older adult and
      younger cohorts prescribed MDIs in error types. There is evidence of age
      associated differences in the number and type of inhaler technique errors.
      Further research is required to assess outcomes in individual DPIs,
      reproducibility and the effects of confounders.

PMID- 29212837
TI  - Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.
AB  - Pirfenidone is one of two approved therapies for the treatment of idiopathic
      pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent
      post hoc analyses have demonstrated that pirfenidone reduces lung function
      decline, decreases mortality and improves progression-free survival. Long-term
      extension trials, registries and real-world studies have also shown similar
      treatment effects with pirfenidone. However, for patients with IPF to obtain the
      maximum benefits of pirfenidone treatment, the potential adverse events (AEs)
      associated with pirfenidone need to be managed. This review highlights the well
      known and established safety profile of pirfenidone based on randomised
      controlled clinical trials and real-world data. Key strategies for preventing and
      managing the most common pirfenidone-related AEs are described, with the goal of
      maximising adherence to pirfenidone with minimal AEs.

PMID- 29212838
TI  - Long-term macrolides in diffuse interstitial lung diseases.
AB  - In the present review we provide currently available evidence for the use of
      macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to
      now, research on macrolides has mainly focused on three areas. First, macrolides
      have shown some promising results in cellular models and case reports as
      antifibrotic agents, by promoting autophagy and clearance of intracellular
      protein aggregates and acting as regulators of surfactant homeostasis. Secondly,
      macrolides have an immunomodulatory effect, which has been applied in some
      organising pneumonia cases. In particular, macrolides have been tested in
      association with systemic corticosteroids as steroid-sparing agents and alone as
      either first-line agents in mild cases or second-line agents where steroids were
      poorly tolerated or had failed. Thirdly, a recent area of research concerns the
      possible role of macrolides as modulators of lung microbiota and the host
      microbiota interaction. This function has been particularly studied in idiopathic
      pulmonary fibrosis patients, in whom changes in microbiota have been proved to be
      associated with disease progression. However, the lack of high-quality studies
      makes the application of macrolide therapy in ILDs a field in which research
      should be conducted on a large scale.

PMID- 29212840
TI  - Life's a Gas under Pressure: Ethylene and Etioplast Maintenance in Germinating
      Seedlings.

PMID- 29212839
TI  - BP in Dialysis: Results of a Pilot Study.
AB  - The optimal BP target for patients receiving hemodialysis is unknown. We
      randomized 126 hypertensive patients on hemodialysis to a standardized
      predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard
      arm). The primary objectives were to assess feasibility and safety and inform the
      design of a full-scale trial. A secondary objective was to assess changes in left
      ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week
      moving average systolic BP did not change significantly during the intervention
      period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline
      to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP
      between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one
      death occurred in the standard arm. The incidence rate ratios for the intensive
      compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to
      3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse
      cardiovascular events, hospitalizations, and vascular access thrombosis,
      respectively. The intensive and standard arms had similar median changes (95%
      confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4
      (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal,
      the small size and short duration of the trial prevent definitive conclusions.
      Considering the high risk for major adverse cardiovascular events in patients
      receiving hemodialysis, a full-scale trial is needed to assess potential benefits
      of intensive hypertension control in this population.

PMID- 29212841
TI  - Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama
      pigs.
AB  - Decompression sickness (DCS) occurs when ambient pressure is severely reduced
      during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown
      to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We
      hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models.
      In the first part of our investigation, six swine were subjected to a session of
      HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24
      and 30 h following exposure in lymphocytes. In the second part of our
      investigation, another 10 swine were randomly assigned into two groups (five per
      group). All swine were subjected to two simulated air dives in a hyperbaric
      chamber with an interval of 7 days. Eighteen hours before each dive, the swine
      were pretreated with HBO or air: the first group received air pretreatment prior
      to the first dive and HBO pretreatment prior to the second; the second group were
      pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation
      and endothelial markers were detected after each dive. In lymphocytes, all HSPs
      increased significantly (P<0.05), with the greatest expression appearing at 18 h
      for HSP32 and 70. HBO pretreatment significantly reduced all the determined
      changes compared with air pretreatment. The results demonstrate that a single
      exposure to HBO 18 h prior to diving effectively protects against DCS in the
      swine model, possibly via induction of HSPs.

PMID- 29212842
TI  - Lean, mean, lipolytic machines: lipid mobilization in rainbow trout during graded
      swimming.
AB  - The mobilization of mammalian lipid reserves is strongly stimulated during
      exercise to reach a maximum at moderate intensities, but the effects of swimming
      speed on fish lipolysis have never been quantified. Continuous infusion of 2
      [3H]glycerol was used to measure the rate of appearance of glycerol or lipolytic
      rate (Ra glycerol) in rainbow trout kept at rest, or during graded exercise in a
      swim tunnel up to critical swimming speed (Ucrit). Results show that Ra glycerol
      is 1.67+/-0.18 umol kg-1 min-1 in control animals, and remains at a steady level
      of 1.24+/-0.10 umol kg-1 min-1 in exercising fish at all swimming intensities.
      Baseline lipolytic rate provides more than enough fatty acids from lipid reserves
      to accommodate all the oxidative fuel requirements for swimming at up to 2 body
      lengths per second (BL s-1), and more than 50% of the energy needed at Ucrit
      (3.4+/-0.1 BL s-1). Such 'excess lipolysis' also means that trout sustain high
      rates of fatty acid reesterification. Maintaining steady lipolysis at rest and
      throughout graded swimming is strikingly different from mammals that stimulate Ra
      glycerol by twofold to fivefold to support exercise. Instead, trout act like
      'lipolytic machines' that do not modulate Ra glycerol even when their metabolic
      rate triples - a strategy that eliminates the need to increase lipolytic rate
      during exercise. This study also supports the notion that maintaining a high rate
      of reesterification (or triacylglycerol/fatty acid cycling) may be a mechanism
      widely used by ectotherms to achieve rapid membrane remodelling in variable
      environments.

PMID- 29212843
TI  - Movements of vastly different performance have similar underlying muscle
      physiology.
AB  - Many animals use elastic recoil mechanisms to power extreme movements, achieving
      levels of performance that would not be possible using muscle power alone.
      Contractile performance of vertebrate muscle depends strongly on temperature, but
      the release of energy from elastic structures is far less thermally dependent,
      thus elastic recoil confers thermal robustness to whole-animal performance. Here
      we explore the role that muscle contractile properties play in the differences in
      performance and thermal robustness between elastic and non-elastic systems by
      examining muscle from two species of plethodontid salamanders that use
      elastically powered tongue projection to capture prey and one that uses non
      elastic tongue projection. In species with elastic mechanisms, tongue projection
      is characterized by higher mechanical power output and thermal robustness
      compared with tongue projection of closely related genera with non-elastic
      mechanisms. In vitro and in situ muscle experiments reveal that species differ in
      their muscle contractile properties, but these patterns do not predict the
      performance differences between elastic and non-elastic tongue projection.
      Overall, salamander tongue muscles are similar to other vertebrate muscles in
      contractile performance and thermal sensitivity. We conclude that changes in the
      tongue-projection mechanism, specifically the elaboration of elastic structures,
      are responsible for high performance and thermal robustness in species with
      elastic tongue projection. This suggests that the evolution of high-performance
      and thermally robust elastic recoil mechanisms can occur via relatively simple
      changes to morphology, while muscle contractile properties remain relatively
      unchanged.

PMID- 29212844
TI  - Protein synthesis is lowered by 4EBP1 and eIF2-alpha signaling while protein
      degradation may be maintained in fasting, hypoxic Amazonian cichlids Astronotus
      ocellatus.
AB  - The Amazonian cichlid Astronotus ocellatus is highly tolerant to hypoxia, and is
      known to reduce its metabolic rate by reducing the activity of energetically
      expensive metabolic processes when oxygen is lacking in its environment. Our
      objectives were to determine how protein metabolism is regulated in A. ocellatus
      during hypoxia. Fish were exposed to a stepwise decrease in air saturation (100%,
      20%, 10% and 5%) for 2 h at each level, and sampled throughout the experiment. A
      flooding dose technique using a stable isotope allowed us to observe an overall
      decrease in protein synthesis during hypoxia in liver, muscle, gill and heart. We
      estimate that this decrease in rates of protein synthesis accounts for a 20 to
      36% decrease in metabolic rate, which would enable oscars to maintain stable
      levels of ATP and prolong survival. It was also determined for the first time in
      fish that a decrease in protein synthesis during hypoxia is likely controlled by
      signaling molecules (4EBP1 and eIF2-alpha), and not simply due to a lack of ATP.
      We could not detect any effects of hypoxia on protein degradation as the levels
      of NH4 excretion, indicators of the ubiquitin proteasome pathway, and enzymatic
      activities of lysosomal and non-lysosomal proteolytic enzymes were maintained
      throughout the experiment.

PMID- 29212845
TI  - Crawling without wiggling: muscular mechanisms and kinematics of rectilinear
      locomotion in boa constrictors.
AB  - A central issue for understanding locomotion of vertebrates is how muscle
      activity and movements of their segmented axial structures are coordinated, and
      snakes have a longitudinal uniformity of body segments and diverse locomotor
      behaviors that are well suited for studying the neural control of rhythmic axial
      movements. Unlike all other major modes of snake locomotion, rectilinear
      locomotion does not involve axial bending, and the mechanisms of propulsion and
      modulating speed are not well understood. We integrated electromyograms and
      kinematics of boa constrictors to test Lissmann's decades-old hypotheses of
      activity of the costocutaneous superior (CCS) and inferior (CCI) muscles and the
      intrinsic cutaneous interscutalis (IS) muscle during rectilinear locomotion. The
      CCI was active during static contact with the ground as it shortened and pulled
      the axial skeleton forward relative to both the ventral skin and the ground
      during the propulsive phase. The CCS was active during sliding contact with the
      ground as it shortened and pulled the skin forward relative to both the skeleton
      and the ground during the recovery phase. The IS shortened the ventral skin, and
      subsequent isometric activity kept the skin stiff and shortened during most of
      static contact while overlapping extensively with CCI activity. The concentric
      activity of the CCI and CCS supported Lissmann's predictions. Contrary to
      Lissmann, the IS had prolonged isometric activity, and the time when it shortened
      was not consistent with providing propulsive force. Decoupling propulsion from
      axial bending in rectilinear locomotion may have facilitated economical
      locomotion of early snakes in subterranean tunnels.

PMID- 29212846
TI  - Associations of Del 301-303 alpha2B-adrenoceptor gene polymorphism with central
      hemodynamic parameters in the northern Russian population.
AB  - The ADRA2B gene 301-303 I/D polymorphism is associated with various
      cardiovascular phenotypes. However, an association of genotypes with the timing
      structure of cardiac cycle remains unclear. The central hemodynamic parameters
      were assessed by pulse wave analysis in 63 residents of the Kola Peninsula (68 N)
      aged 27-65 yr. The genotypes were determined by PCR. The paired comparisons
      revealed that II genotype carriers had higher values of augmentation index ( P =
      0.014), ejection duration ( P = 0.045), and lower SEVR ( P = 0.035) than DD
      homozygotes. Multiple regression analysis adjusted for age, body mass index,
      heart rate, and blood pressure confirmed these results. Further sex stratified
      analysis showed that the associations existed only in men ( n = 33) whereas in
      women ( n = 30) the differences were suggestive ( P < 0.1). It is concluded that
      in a northern Russian population men carrying I allele have stiffer arteries,
      shorter diastole duration, and impaired coronary perfusion and seem to be at
      higher risk for cardiovascular diseases than DD carriers.

PMID- 29212847
TI  - Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse
      events during aromatase inhibitor treatment for breast cancer.
AB  - Aromatase inhibitor (AI) therapy is highly efficacious in the treatment of
      estrogen receptor-positive breast cancer; however, in a subset of patients AI use
      is discontinued due to drug-induced musculoskeletal adverse events (MS-AE).
      Several studies have investigated the role of germline single nucleotide
      polymorphisms (SNPs) on patients' risk of MS-AEs; however, no associations have
      yet to be validated for translation into clinical practice. This study attempted
      to replicate SNPs in RANKL ( rs7984870 ) and OPG ( rs2073618 ) on the risk of AI
      induced MS-AEs and screen for secondary associations with MS-AE-related treatment
      discontinuation and serum and urine markers of bone health. Previously reported
      associations were not replicated with our primary hypothesis, change in MS-AE
      from baseline to 3 mo; however, patients homozygous for the G allele of rs7984870
      in RANKL had lower risk of MS-AE-associated treatment discontinuation in analyses
      of secondary phenotypes without statistical correction.

PMID- 29212848
TI  - Association of complement receptor 1 gene polymorphisms with cognitive function.
AB  - Previous evidence suggest involvement of the complement receptor 1 (CR1) in
      development of Alzheimer's disease. We investigated the association of CR1 gene
      polymorphisms with cognitive function in older subjects. Single nucleotide
      polymorphisms (SNPs) within the CR1 region on chromosome 1 ( n = 73) were
      assessed in 5,244 participants in the PROspective Study of Pravastatin in the
      Elderly at Risk (51.9% female, mean age 75.3 yr). Linear regression, adjusted for
      age, sex, country, and use of pravastatin, was used to assess the association
      between the SNPs and cognitive function. All 73 SNPs within the genomic region of
      the CR1 gene on chromosome 1 were extracted. Eighteen were independent, according
      to a relatively stringent R2 threshold of >0.8 with LDlink. Twelve of the 18
      investigated CR1 SNPs were significantly associated with a decline in cognitive
      function (all P < 0.05). These data indicate that genetic variation within the
      CR1 gene is associated not only with Alzheimer's disease, but also with general
      cognitive function during late life.

PMID- 29212849
TI  - TRIM63 (MuRF-1) gene polymorphism is associated with biomarkers of exercise
      induced muscle damage.
AB  - Unaccustomed strenuous exercise can lead to muscle strength loss, inflammation
      and delayed-onset muscle soreness, which may be influenced by genetic variation.
      We investigated if a missense single nucleotide polymorphism (A>G, rs2275950 )
      within the TRIM63 gene (encoding MuRF-1 and potentially affecting titin
      mechanical properties) was associated with the variable response to unaccustomed
      eccentric exercise. Sixty-five untrained, healthy participants (genotyped for
      rs2275950 : AA, AG, and GG) performed 120 maximal eccentric knee extensions (ECC)
      to induce muscle damage. Isometric and isokinetic maximal voluntary knee
      extension contractions (MVCs) and muscle soreness were assessed before,
      immediately after, and 48 h after ECC. AA homozygotes were consistently stronger
      [baseline isometric MVC: 3.23 +/- 0.92 Nm/kg (AA) vs. 2.09 +/- 0.67 Nm/kg (GG); P
      = 0.006] and demonstrated less muscle soreness over time ( P = 0.022) compared
      with GG homozygotes. This may be explained by greater titin stiffness in AA
      homozygotes, leading to intrinsically stronger muscle fibers that are more
      resistant to eccentric damaging contractions.

PMID- 29212850
TI  - Endothelial transcriptomics reveals activation of fibrosis-related pathways in
      hypertension.
AB  - Hypertension poses a significant challenge to vasculature homeostasis and stands
      as the most common cardiovascular disease in the world. Its effects are
      especially profound on endothelial cells that form the inner lining of the
      vasculature and are directly exposed to the effects of excess pressure. Here, we
      characterize the in vivo transcriptomic response of cardiac endothelial cells to
      hypertension by rapidly isolating these cells from the spontaneous hypertension
      mouse model BPH/2J and its normotensive BPN/3J control strain and performing and
      RNA sequencing on both. Comparison of transcriptional differences between these
      groups reveals statistically significant changes in cellular pathways consistent
      with cardiac fibrosis found in hypertensive animals. Importantly, many of the
      fibrosis-linked genes identified also differ significantly between juvenile
      prehypertensive and adult hypertensive BPH/2J mice, suggesting that these
      transcriptional differences are hypertension related. We examined the dynamic
      nature of these transcriptional changes by testing whether blood pressure
      normalization using either a calcium channel blocker (amlodipine) or a
      angiotensin II receptor blocker (losartan) is able to reverse these expression
      patterns associated with hypertension. We find that blood pressure reduction is
      capable of reversing some gene-expression patterns, while other transcripts are
      recalcitrant to therapeutic intervention. This illuminates the possibility that
      unmanaged hypertension may irreversibly alter some endothelial transcriptional
      patterns despite later intervention. This study quantifies how endothelial cells
      are remodeled at the molecular level in cardiovascular pathology and advances our
      understanding of the transcriptional events associated with endothelial response
      to hypertensive challenge.

PMID- 29212851
TI  - Omics of bifidobacteria: research and insights into their health-promoting
      activities.
AB  - Members of the genus Bifidobacterium include gut commensals that are particularly
      abundant among the microbial communities residing in the gut of healthy breast
      fed infants, where their presence has been linked to many beneficial host
      effects. Next-generation DNA sequencing and comparative and functional genome
      methodologies have been shown to be particularly useful in exploring the
      diversity of this genus. These combined approaches have allowed the
      identification of genetic features related to bifidobacterial establishment in
      the gut, involving host-microbe as well as microbe-microbe interactions. Among
      these, proteinaceous structures, which protrude from the bacterial surface, i.e.
      pili or fimbriae, and exopolysaccharidic cell surface layers or capsules
      represent crucial features that assist in their colonization and persistence in
      the gut. As bifidobacteria are colonizers of the large intestine, they have to be
      able to cope with various sources of osmotic, oxidative, bile and acid stress
      during their transit across the gastric barrier and the small intestine.
      Bifidobacterial genomes thus encode various survival mechanisms, such as
      molecular chaperones and efflux pumps, to overcome such challenges.
      Bifidobacteria represent part of an anaerobic gut community, and feed on
      nondigestible carbohydrates through a specialized fermentative metabolic pathway,
      which in turn produces growth substrates for other members of the gut community.
      Conversely, bifidobacteria may also be dependent on other (bifido)bacteria to
      access host- and diet-derived glycans, and these complex co-operative
      interactions, based on resource sharing and cross-feeding strategies, represent
      powerful driving forces that shape gut microbiota composition.

PMID- 29212852
TI  - A Systems Approach to Prostate Cancer Classification-Letter.

PMID- 29212853
TI  - Emergence of High-Avidity Melan-A-Specific Clonotypes as a Reflection of Anti-PD
      1 Clinical Efficacy.
AB  - Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled
      effectiveness for melanoma immunotherapy, but deciphering immune responses
      modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the
      composition and functions of the large Melan-A-specific T-cell repertoire in the
      peripheral blood of 9 melanoma patients before and after 2 months of treatment
      with anti-PD-1. We observed amplification of Melan-A-specific Vbeta subfamilies
      undetectable before therapy (thereafter called emerging Vbeta subfamilies) in
      responding patients, with a predominant expansion in patients with a complete
      response. These emerging Vbeta subfamilies displayed a higher functional avidity
      for their cognate antigen than Vbeta subfamilies not amplified upon anti-PD-1
      therapy and could be identified by a sustained coexpression of PD-1 and TIGIT
      receptors. Thus, in addition to the emergence of neoantigen-specific T cells
      previously documented upon anti-PD-1 therapy, our work describes the emergence of
      high-avidity Melan-A-specific clonotypes as a surrogate marker of treatment
      efficacy. Cancer Res; 77(24); 7083-93. (c)2017 AACR.

PMID- 29212854
TI  - A Systems Approach to Prostate Cancer Classification-Response.

PMID- 29212855
TI  - T-Cell Densities in Brain Metastases Are Associated with Patient Survival Times
      and Diffusion Tensor MRI Changes.
AB  - Brain metastases are common and are usually detected by MRI. Diffusion tensor
      imaging (DTI) is a derivative MRI technique that can detect disruption of white
      matter tracts in the brain. We have matched preoperative DTI with image-guided
      sampling of the brain-tumor interface in 26 patients during resection of a brain
      metastasis and assessed mean diffusivity and fractional anisotropy (FA). The
      tissue samples were analyzed for vascularity, inflammatory cell infiltration,
      growth pattern, and tumor expression of proteins associated with growth or local
      invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral
      region indicated more white matter tract disruption and independently predicted
      longer overall survival times (HR for death = 0.21; 95% confidence interval, 0.06
      0.82; P = 0.024). Of all the biological markers studied, only increased density
      of CD3+ lymphocytes in the same region correlated with decreased FA (Mann-Whitney
      U, P = 0.037) as well as confounding completely the effect of FA on multivariate
      survival analyses. We conclude that the T-cell response to brain metastases is
      not a surrogate of local tumor invasion, primary cancer type, or aggressive
      phenotype and is associated with patient survival time regardless of these
      biological factors. Furthermore, it can be assayed by DTI, potentially offering a
      quick, noninvasive, clinically available method to detect an active immune
      microenvironment and, in principle, to measure susceptibility to
      immunotherapy.Significance: These findings show that white matter tract integrity
      is degraded in areas where T-cell infiltration is highest, providing a
      noninvasive method to identify immunologically active microenvironments in
      secondary brain tumors. Cancer Res; 78(3); 610-6. (c)2017 AACR.

PMID- 29212856
TI  - Tamoxifen Resistance in Breast Cancer Is Regulated by the EZH2-ERalpha-GREB1
      Transcriptional Axis.
AB  - Resistance to cancer treatment can be driven by epigenetic reprogramming of
      specific transcriptomes in favor of the refractory phenotypes. Here we discover
      that tamoxifen resistance in breast cancer is driven by a regulatory axis
      consisting of a master transcription factor, its cofactor, and an epigenetic
      regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen
      resistance by silencing the expression of the estrogen receptor alpha (ERalpha)
      cofactor GREB1. In clinical specimens, induction of DNA methylation of a
      particular CpG-enriched region at the GREB1 promoter negatively correlated with
      GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper
      cellular reactions to different ligands by recruiting distinct sets of ERalpha
      cofactors to cis-regulatory elements, which explains the contradictory biological
      effects of GREB1 on breast cancer cell growth in response to estrogen or
      antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered
      chromatin reallocation of ERalpha coregulators, converting the antiestrogen into
      an agonist. In clinical specimens from patients receiving adjuvant tamoxifen
      treatment, expression levels of EZH2 and GREB1 were correlated negatively, and
      taken together better predicted patient responses to endocrine therapy. Overall,
      our work suggests a new strategy to overcome endocrine resistance in metastatic
      breast cancer by targeting a particular epigenetic program.Significance: This
      study suggests a new strategy to overcome endocrine resistance in metastatic
      breast cancer by targeting a particular epigenetic program defined within. Cancer
      Res; 78(3); 671-84. (c)2017 AACR.

PMID- 29212857
TI  - Mutational Mechanisms That Activate Wnt Signaling and Predict Outcomes in
      Colorectal Cancer Patients.
AB  - APC biallelic loss-of-function mutations are the most prevalent genetic changes
      in colorectal tumors, but it is unknown whether these mutations phenocopy gain-of
      function mutations in the CTNNB1 gene encoding beta-catenin that also activate
      canonical WNT signaling. Here we demonstrate that these two mutational mechanisms
      are not equivalent. Furthermore, we show how differences in gene expression
      produced by these different mechanisms can stratify outcomes in more advanced
      human colorectal cancers. Gene expression profiling in Apc-mutant and Ctnnb1
      mutant mouse colon adenomas identified candidate genes for subsequent evaluation
      of human TCGA (The Cancer Genome Atlas) data for colorectal cancer outcomes.
      Transcriptional patterns exhibited evidence of activated canonical Wnt signaling
      in both types of adenomas, with Apc-mutant adenomas also exhibiting unique
      changes in pathways related to proliferation, cytoskeletal organization, and
      apoptosis. Apc-mutant adenomas were characterized by increased expression of the
      glial nexin Serpine2, the human ortholog, which was increased in advanced human
      colorectal tumors. Our results support the hypothesis that APC-mutant colorectal
      tumors are transcriptionally distinct from APC-wild-type colorectal tumors with
      canonical WNT signaling activated by other mechanisms, with possible implications
      for stratification and prognosis.Significance: These findings suggest that colon
      adenomas driven by APC mutations are distinct from those driven by WNT gain-of
      function mutations, with implications for identifying at-risk patients with
      advanced disease based on gene expression patterns. Cancer Res; 78(3); 617-30.
      (c)2017 AACR.

PMID- 29212858
TI  - Decreased EDHF-mediated relaxation is a major mechanism in endothelial
      dysfunction in resistance arteries in aged mice on prolonged high-fat sucrose
      diet.
AB  - High-fat sucrose (HFS) diet in aged individuals causes severe weight gain
      (obesity) with much higher risk of cardiovascular diseases such as hypertension
      or atherosclerosis. Endothelial dysfunction is a major contributor for these
      vascular disorders. We hypothesize that prolonged ingestion of HFS diet by aged
      mice would accentuate endothelial dysfunction in the small resistance arteries.
      Male C57BL/6J mice at 12 weeks of age were divided into four groups and fed
      either normal chow (NC) or high-fat sucrose diet (HFS). Young group received NC
      for 4 months, and high-fat diet (HFD) for 3 months and 1 month HFS + 10% Sucrose
      (HFS diet). Aged mice received NC for 12 months. Aged HFS group received HFD for
      4 months + 1 month HFD + 10% sucrose + 8 months HFD. Total body weight, plasma
      blood glucose levels, and glucose tolerance were determined in all groups.
      Isolated mesenteric arteries were assessed for arterial remodeling, myogenic
      tone, and vasomotor responses using pressure and wire myography. Both young and
      aged HFS mice showed impaired glucose tolerance (Y-NC, 137 +/- 8.5 vs. Y-NC HFS,
      228 +/- 11.71; A-NC, 148 +/- 6.42 vs. A-HFS, 225 +/- 10.99), as well as
      hypercholesterolemia (Y-NC 99.50 +/- 6.35 vs. Y-HFS 220.40 +/- 16.34 mg/dL; A-NC
      108.6 +/- vs. A-HFS 279 +/- 21.64) and significant weight gain (Y-NC 32.13 +/-
      0.8 g vs. Y-HFS 47.87 +/- 2.18 g; A-NC 33.72 vs. A-HFS 56.28 +/- 3.47 g) compared
      to both groups of mice on NC. The mesenteric artery from mice with prolonged HFS
      diet resulted in outward hypertrophic remodeling, increased stiffness, reduced
      myogenic tone, impaired vasodilation, increased contractility and blunted nitric
      oxide (NO) and EDH-mediated relaxations. Ebselen, a peroxinitrite scavenger
      rescued the endothelium derived relaxing factor (EDHF)-mediated relaxations. Our
      findings suggest that prolonged diet-induced obesity of aged mice can worsen
      small resistance artery endothelial dysfunction due to decrease in NO and EDHF
      mediated relaxation, but, EDHF-mediated relaxation is a major contributor to
      overall endothelial dysfunction.

PMID- 29212859
TI  - Human hair follicle transcriptome profiling: a minimally invasive tool to assess
      molecular adaptations upon low-volume, high-intensity interval training.
AB  - High-intensity interval training (HIIT) has become a popular fitness training
      approach under both civilian and military settings. Consisting of brief and
      intense exercise intervals, HIIT requires less time commitment yet is able to
      produce the consistent targeted physical adaptations as conventional endurance
      training. To effectively characterize and monitor HIIT-induced cellular and
      molecular responses, a highly accessible yet comprehensive biomarker discovery
      source is desirable. Both gene differential expression (DE) and gene set (GS)
      analyses were conducted using hair follicle transcriptome established from pre
      and postexercise subjects upon a 10-day HIIT program by RNA-Seq, Comparing
      between pre and posttraining groups, differentially expressed protein coding
      genes were identified. To interpret the functional significance of the DE
      results, a comprehensive GS analysis approach featuring multiple algorithms was
      used to enrich gene ontology (GO) terms and KEGG pathways. The GS analysis
      revealed enriched themes such as energy metabolism, cell
      proliferation/growth/survival, muscle adaptations, and cytokine-cytokine
      interaction, all of which have been previously proposed as HIIT responses.
      Moreover, related cell signaling pathways were also measured. Specifically, G
      protein-mediated signal transduction, phosphatidylinositide 3-kinases (PI3K) -
      protein kinase B (PKB) and Janus kinase (JAK) - Signal Transducer and Activator
      of Transcription (STAT) signaling cascades were over-represented. Additionally,
      the RNA-Seq analysis also identified several HIIT-responsive microRNAs (miRNAs)
      that were involved in regulating hair follicle-specific processes, such as miR
      99a For the first time, this study demonstrated that both existing and new
      biomarkers like miRNA can be explored for HIIT using the transcriptomic responses
      exhibited by the hair follicle.

PMID- 29212860
TI  - Reference values of renal tubular function tests are dependent on age and kidney
      function.
AB  - Electrolyte disorders due to tubular disorders are rare, and knowledge about
      validated clinical diagnostic tools such as tubular function tests is sparse.
      Reference values for tubular function tests are based on studies with small
      sample size in young healthy volunteers. Patients with tubular disorders,
      however, frequently are older and can have a compromised renal function. We
      therefore evaluated four tubular function tests in individuals with different
      ages and renal function. We performed furosemide, thiazide, furosemide
      fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years,
      healthy individuals aged more than 50 years and individuals with compromised
      renal function. For each tubular function test we included 10 individuals per
      group. The responses in young healthy individuals were in line with previously
      reported values in literature. The maximal increase in fractional chloride
      excretion after furosemide was below the lower limit of young healthy individuals
      in 5/10 older subjects and in 2/10 patients with compromised renal function. The
      maximal increase in fractional chloride excretion after thiazide was below the
      lower limit of young healthy individuals in 6/10 older subjects and in 7/10
      patients with compromised renal function. Median maximal urine osmolality after
      desmopressin was 1002 mosmol/kg H2O in young healthy individuals, 820 mosmol/kg
      H2O in older subjects and 624 mosmol/kg H2O in patients with compromised renal
      function. Reference values for tubular function tests obtained in young healthy
      adults thus cannot simply be extrapolated to older patients or patients with
      compromised kidney function. Larger validation studies are needed to define true
      reference values in these patient categories.

PMID- 29212861
TI  - Dissecting spinal aneurysms: conservative management as a therapeutic option.
AB  - OBJECTIVE: Isolated dissecting spinal aneurysms are rare lesions that pose a
      therapeutic challenge. We report our experience in the management of four
      patients with dissecting spinal aneurysms. METHODS: After institutional review
      board approval was obtained, the neurointerventional databases of the two
      participating institutions were retrospectively reviewed. Aneurysms in the
      anterior spinal artery, posterior spinal artery, or in a radiculomedullary artery
      were included in the analysis. Flow-related aneurysms were excluded. Data on
      clinical presentation, hemorrhage location, aneurysm size, location, angiographic
      follow-up, re-hemorrhage, and clinical outcome were obtained and analyzed.
      RESULTS: Four patients with five spinal dissecting aneurysms met the inclusion
      criteria. There were two women and the mean age was 63 years (range 36-64). All
      patients presented with hemorrhage. Three radiculomedullary arteries in two
      different patients had one lesion each; the other two involved the anterior
      spinal artery and a posterior spinal artery in different patients. All four
      patients were managed conservatively. Follow-up angiography (5.5 months)
      demonstrated occlusion of all five aneurysms. There was no re-hemorrhage and all
      patients had a good outcome at the last follow-up (modified Rankin Scale score 0
      2). CONCLUSIONS: Conservative management of ruptured spontaneous dissecting
      spinal aneurysms is a reasonable therapeutic option capable of achieving
      favorable angiographic and clinical outcomes.

PMID- 29212862
TI  - Ataxia with oculomotor apraxia type 2: an evolving axonal neuropathy.
AB  - A 23-year-old woman had presented initially to a podiatrist complaining of poorly
      fitting shoes during her adolescence. After extensive neurological review, she
      was diagnosed with ataxia with oculomotor apraxia type 2. This is a progressive
      autosomal recessive ataxia associated with cerebellar atrophy, peripheral
      neuropathy and an elevated serum alpha-fetoprotein. Within Europe, it is the most
      frequent autosomal recessive ataxia after Friedreich's ataxia and is due to
      mutations in the senataxin (SETX) gene. The age of onset is approximately 15
      years.The diagnosis of oculomotor apraxia type 2 is often challenging. We provide
      a framework for assessing a young ataxic patient with or without oculomotor
      apraxia and review clues that will aid diagnosis. The prognosis, level of
      disability, cancer and immunosuppression risk all markedly differ between the
      conditions. Patients and their families need the correct diagnosis for genetic
      counselling, management and long-term surveillance with appropriate subspecialty
      services.

PMID- 29212863
TI  - Modelling the implications of reducing smoking prevalence: the benefits of
      increasing the UK tobacco duty escalator to public health and economic outcomes.
AB  - INTRODUCTION: Taxing tobacco is one of the most effective ways to reduce smoking
      prevalence, mitigate its devastating consequential health harms and progress
      towards a tobacco-free society. This study modelled the health and economic
      impacts of increasing the existing cigarette tobacco duty escalator (TDE) in the
      UK from the current 2% above consumer price inflation to 5%. METHODS: A two-stage
      modelling process was used. First, a non-linear multivariate regression model was
      fitted to cross-sectional smoking data, creating longitudinal projections from
      2015 to 2035. Second, these projections were used to predict the future
      incidence, prevalence and cost of 17 smoking-related diseases using a Monte Carlo
      microsimulation approach. A sustained increase in the duty escalator was
      evaluated against a baseline of continuing historical smoking trends and the
      existing duty escalator. RESULTS: A sustained increase in the TDE is projected to
      reduce adult smoking prevalence to 6% in 2035, from 10% in a baseline scenario.
      After increasing the TDE, only 65% of female and 60% of male would-be smokers
      would actually be smoking in 2035. The intervention is projected to avoid around
      75 200 new cases of smoking-related diseases between 2015 and 2035. In 2035
      alone, L49 m in National Health Service and social care costs and L192 m in
      societal premature mortality and morbidity costs are projected to be avoided.
      CONCLUSION: Increasing the UK TDE to 5% above inflation could effectively reduce
      smoking prevalence, prevent diseases and avoid healthcare costs. It would deliver
      substantial progress towards a tobacco-free society and should be implemented by
      the UK Government with urgency.

PMID- 29212864
TI  - Morning sickness is just the side effect of a new tachykinin that the placenta
      secretes to improve local blood flow.

PMID- 29212865
TI  - The placenta controls the physiology of pregnancy by increasing the half-life in
      blood and receptor activity of its secreted peptide hormones.
AB  - An efficient functioning placenta is essential for a healthy pregnancy and yet
      the way this is achieved has been the subject of much discussion and confusion,
      particularly with the occurrence of pathological conditions such as preeclampsia,
      morning sickness and hyperemesis/ptyalism gravidarum. We will attempt to explain
      the underlying physiology and the potential roles played by the placental
      tachykinins, neurokinin B and endokinin.

PMID- 29212866
TI  - Acquired haemophilia A complicating alemtuzumab therapy for multiple sclerosis.
AB  - Alemtuzumab is a highly efficacious therapy used in the treatment of multiple
      sclerosis (MS), but uncoupling of T and B cell repopulation during immune
      reconstitution associates with an increasing range of secondary B cell-mediated
      autoimmune complications. A 34-year-old woman developed Graves' disease 11 months
      following an initial course of alemtuzumab treatment for MS. Nine months
      following the second treatment with alemtuzumab, the patient presented with
      spontaneous intramuscular and subcutaneous haemorrhage due to development of an
      inhibitory autoantibody to coagulation factor VIII. Acquired haemophilia A (AHA)
      is an extremely rare complication in patients treated with alemtuzumab. Treatment
      with rituximab may induce a rapid remission of AHA; however, the patient's high
      John Cunningham virus (JCV) antibody index and alemtuzumab-induced T cell
      lymphopenia may lead to an increased risk of progressive multifocal
      leucoencephalopathy, a potential complication which was unacceptable to the
      patient.

PMID- 29212867
TI  - Dysphagia lusoria presenting as epigastric pain.

PMID- 29212868
TI  - Painful testicular metastasis from prostate adenocarcinoma.
AB  - A 60-year-old man presented with unilateral testicular pain and urinary
      frequency. His presenting prostate-specific antigen (PSA) was 100 ng/mL, and a
      biopsy revealed Gleason 4+4 prostate adenocarcinoma. The significance of his
      initial PSA was somewhat complicated by possible prostatitis and early initiation
      of bicalutamide. PSA rose on two occasions prior to radiotherapy but coincided
      with a flare of testicular pain on one of these. Whole-body staging diffusion
      weighted MRI scan was negative. He was treated with 3 years of androgen
      deprivation therapy (ADT) and radical radiotherapy. PSA fell to undetectable
      levels on ADT. Twelve months following completion of ADT, PSA rose to 3.6 ng/mL.
      No disease recurrence was noted on restaging MRI pelvis. The patient was well,
      except for persistent testicular symptoms, which failed to resolve following
      multiple antibiotics. Testicular tumour markers were negative. Ultrasound
      findings were consistent with chronic epididymitis. A right orchidectomy was
      performed for symptomatic relief, confirming metastatic prostate adenocarcinoma.

PMID- 29212869
TI  - Nerve abscess in pure neural leprosy mistaken for peripheral nerve sheath tumour
      with disastrous consequence: what can we learn?
AB  - A 34-year-old Indian man presented to an orthopaedician with gradually
      progressive hypoesthesia affecting his right lower limb and an ipsilateral common
      peroneal nerve swelling around the knee. The nerve swelling was diagnosed as a
      peripheral nerve sheath tumour based on MRI findings and was excised, only to be
      revealed as leprous nerve abscess on histopathology later. The patient developed
      right foot drop as a result of common peroneal nerve biopsy. This case presents
      several learning points in the diagnosis of pure neural leprosy.

PMID- 29212870
TI  - Pathological ECG that seemed normal following electrode misplacement.
AB  - We report the case of a 57-year-old woman found at home who received an ECG after
      having recovered from a seizure, without any clinical cardiac anomaly. The ECG
      revealed an elevation of the ST segment from the V1 to V5 leads and negative T
      waves from V1 to V5 leads. At her hospital admission, the emergency care unit
      (ECU) nurse performed another ECG. It no longer showed any repolarisation
      anomaly. However, the ECU nurse had put the precordial electrodes 3 cm too low,
      probably due to the patient's voluminous breasts. In the end, the pathological
      trace reappeared after we returned the electrodes to their initial positions.
      Malpositioning of the electrodes caused a seemingly normal ECG result with life
      threatening consequences.

PMID- 29212871
TI  - Gastric liposarcoma resected by laparoscopic total gastrectomy to achieve a wide
      surgical margin.
AB  - Gastric liposarcoma is an extremely rare tumour that usually affects the
      extremities and retroperitoneum. Preoperative diagnosis is difficult, and
      operative procedures are not well standardised. A 61-year-old woman presented
      with melaena, epigastric discomfort and palpitations. Upper endoscopy revealed a
      submucosal tumour at the posterior gastric fundus with an actively bleeding ulcer
      on the top. Our preoperative diagnosis was lipoma, and we performed laparoscopic
      intragastric surgery. However, the histopathological diagnosis was liposarcoma.
      Laparoscopic total gastrectomy was performed to achieve a wide surgical margin.
      Several recent series have shown that a positive microscopic margin is associated
      with a higher rate of local recurrence than a negative margin. We have added a
      staged operation to obtain a wide margin in cases involving a positive surgical
      margin. Preoperative diagnosis of liposarcoma is still challenging. Gastric
      lipoma-like tumours should be resected with a wide margin because of their
      possibility of malignancy.

PMID- 29212872
TI  - Parotid gland: an unusual site of breast cancer metastasis.
AB  - Parotid gland metastases from breast cancer are an extremely rare and unusual
      event with a limited number of cases recorded in the literature. A 71-year-old
      woman with a history of ductal adenocarcinoma of the left breast presented to the
      maxillofacial clinic with an asymptomatic swelling of the left parotid gland. The
      presentation occurred 21 years after she underwent treatment for recurrent breast
      cancer. Investigations led to the diagnosis of a breast cancer metastasis which
      was oestrogen receptor and progesterone receptor positive and negative. Positron
      emission tomography scan confirmed this as a solitary metastasis. She was treated
      with aromatase inhibitors and a stable clinical response was observed on follow
      up. Surgical intervention was avoided with its potential complications such as
      facial nerve injury. Metastasis from breast cancer to the parotid gland is a very
      rare phenomenon. However, in a patient with previous breast cancer, it should be
      considered as a possible differential diagnosis.

PMID- 29212873
TI  - Lentiform fork sign due to severe metabolic acidosis.

PMID- 29212874
TI  - The Na+(K+)/H+ exchanger Nhx1 controls multivesicular body-vacuolar lysosome
      fusion.
AB  - Loss-of-function mutations in human endosomal Na+(K+)/H+ exchangers (NHEs) NHE6
      and NHE9 are implicated in neurological disorders including Christianson
      syndrome, autism, and attention deficit and hyperactivity disorder. These
      mutations disrupt retention of surface receptors within neurons and glial cells
      by affecting their delivery to lysosomes for degradation. However, the molecular
      basis of how these endosomal NHEs control endocytic trafficking is unclear. Using
      Saccharomyces cerevisiae as a model, we conducted cell-free organelle fusion
      assays to show that transport activity of the orthologous endosomal NHE Nhx1 is
      important for multivesicular body (MVB)-vacuolar lysosome fusion, the last step
      of endocytosis required for surface protein degradation. We find that deleting
      Nhx1 disrupts the fusogenicity of the MVB, not the vacuole, by targeting pH
      sensitive machinery downstream of the Rab-GTPase Ypt7 needed for SNARE-mediated
      lipid bilayer merger. All contributing mechanisms are evolutionarily conserved
      offering new insight into the etiology of human disorders linked to loss of
      endosomal NHE function.

PMID- 29212875
TI  - IMiQ: a novel protein quality control compartment protecting mitochondrial
      functional integrity.
AB  - Aggregation processes can cause severe perturbations of cellular homeostasis and
      are frequently associated with diseases. We performed a comprehensive analysis of
      mitochondrial quality and function in the presence of aggregation-prone
      polypeptides. Despite a significant aggregate formation inside mitochondria, we
      observed only a minor impairment of mitochondrial function. Detoxification of
      aggregated reporter polypeptides as well as misfolded endogenous proteins inside
      mitochondria takes place via their sequestration into a specific organellar
      deposit site we termed intramitochondrial protein quality control compartment
      (IMiQ). Only minor amounts of endogenous proteins coaggregated with IMiQ deposits
      and neither resolubilization nor degradation by the mitochondrial protein quality
      control system were observed. The single IMiQ aggregate deposit was not
      transferred to daughter cells during cell division. Detoxification of aggregates
      via IMiQ formation was highly dependent on a functional mitochondrial fission
      machinery. We conclude that the formation of an aggregate deposit is an important
      mechanism to maintain full functionality of mitochondria under proteotoxic stress
      conditions.

PMID- 29212876
TI  - Egr-1 mediates leptin-induced PPARgamma reduction and proliferation of pulmonary
      artery smooth muscle cells.
AB  - Loss of peroxisome proliferator-activated receptor gamma (PPARgamma) has been
      found to contribute to pulmonary artery smooth muscle cell (PASMC) proliferation
      and pulmonary arterial remodeling therefore the development of pulmonary
      hypertension (PH). Yet, the molecular mechanisms underlying PPARgamma reduction
      in PASMC remain poorly understood. Here, we demonstrated that leptin dose- and
      time-dependently inducued PPARgamma down-regulation and proliferation of primary
      cultured rat PASMC, this was accompanied with the activation of extracellular
      regulated kinase1/2 (ERK1/2) signaling pathway and subsequent induction of early
      growth response-1 (Egr-1) expression. The presence of MEK inhibitors U0126 or
      PD98059, or prior silencing Egr-1 with small interfering RNA suppressed leptin
      induced PPARgamma reduction. In addition, activation of PPARgamma by pioglitazone
      or targeting ERK1/2/Egr-1 suppressed leptin-induced PASMC proliferation. Taken
      together, our study indicates that ERK1/2 signaling pathway-mediated leptin
      induced PPARgamma reduction and PASMC proliferation through up-regulation of Egr
      1 and suggests that targeting leptin/ERK1/2/Egr-1 pathway might have potential
      value in ameliorating vascular remodeling and benefit PH.

PMID- 29212877
TI  - High-speed superresolution imaging of the proteins in fission yeast clathrin
      mediated endocytic actin patches.
AB  - To internalize nutrients and cell surface receptors via clathrin-mediated
      endocytosis, cells assemble at least 50 proteins, including clathrin, clathrin
      interacting proteins, actin filaments, and actin binding proteins, in a highly
      ordered and regulated manner. The molecular mechanism by which actin filament
      polymerization deforms the cell membrane is unknown, largely due to lack of
      knowledge about the organization of the regulatory proteins and actin filaments.
      We used high-speed superresolution localization microscopy of live fission yeast
      cells to improve the spatial resolution to ~35 nm with 1-s temporal resolution.
      The nucleation promoting factors Wsp1p (WASp) and Myo1p (myosin-I) define two
      independent pathways that recruit Arp2/3 complex, which assembles two zones of
      actin filaments. Myo1p concentrates at the site of endocytosis and initiates a
      zone of actin filaments assembled by Arp2/3 complex. Wsp1p appears simultaneously
      at this site but subsequently moves away from the cell surface as it stimulates
      Arp2/3 complex to assemble a second zone of actin filaments. Cells lacking either
      nucleation-promoting factor assemble only one, stationary, zone of actin
      filaments. These observations support our two-zone hypothesis to explain
      endocytic tubule elongation and vesicle scission in fission yeast.

PMID- 29212880
TI  - Standardizing the Evaluation of Nonaccidental Trauma in a Large Pediatric
      Emergency Department.
AB  - BACKGROUND AND OBJECTIVES: Variability exists in the evaluation of nonaccidental
      trauma (NAT) in the pediatric emergency department because of misconceptions and
      individual bias of clinicians. Further maltreatment, injury, and death can ensue
      if these children are not evaluated appropriately. The implementation of
      guidelines for NAT evaluation has been successful in decreasing differences in
      care as influenced by race and ethnicity of the patient and their family. Our
      Specific, Measurable, Achievable, Realistic, and Timely aim was to increase the
      percent of patients evaluated in the emergency department for NAT who receive
      guideline-adherent evaluation from 47% to 80% by December 31, 2016. METHODS: The
      team determined key drivers for the project and tested them by using multiple
      plan-do-study-act cycles. Interventions included construction of a best practice
      guideline, provider education, integration of the guideline into workflow, and
      order set construction to support guideline recommendations. Data were compiled
      from electronic medical records to identify patients <3 years of age evaluated in
      the pediatric emergency department for suspected NAT based on chart review.
      Adherence to guideline recommendations for age-specific evaluation (<6, 6-12, and
      >12-36 months) was tracked over time on statistical process control charts to
      evaluate the impact of the interventions. RESULTS: A total of 640 encounters had
      provider concern for NAT and were included in the analysis. Adherence to age
      specific guideline recommendations improved from a baseline of 47% to 69%.
      CONCLUSIONS: With our improvement methodology, we successfully increased
      guideline-adherent evaluation for patients with provider concern for NAT.
      Education and electronic support at the point of care were key drivers for
      initial implementation.

PMID- 29212878
TI  - A complex molecular switch directs stress-induced cyclin C nuclear release
      through SCFGrr1-mediated degradation of Med13.
AB  - In response to oxidative stress, cells decide whether to mount a survival or cell
      death response. The conserved cyclin C and its kinase partner Cdk8 play a key
      role in this decision. Both are members of the Cdk8 kinase module, which, with
      Med12 and Med13, associate with the core mediator complex of RNA polymerase II.
      In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which
      thereafter releases cyclin C into the cytoplasm. Cytoplasmic cyclin C associates
      with mitochondria, where it induces hyperfragmentation and regulated cell death.
      In this report, we show that residues 742-844 of Med13's 600-amino acid intrinsic
      disordered region (IDR) both directs cyclin C-Cdk8 association and serves as the
      degron that mediates ubiquitin ligase SCFGrr1-dependent destruction of Med13
      following oxidative stress. Here, cyclin C-Cdk8 phosphorylation of Med13 most
      likely primes the phosphodegron for destruction. Next, pro-oxidant stimulation of
      the cell wall integrity pathway MAP kinase Slt2 initially phosphorylates cyclin C
      to trigger its release from Med13. Thereafter, Med13 itself is modified by Slt2
      to stimulate SCFGrr1-mediated destruction. Taken together, these results support
      a model in which this IDR of Med13 plays a key role in controlling a molecular
      switch that dictates cell fate following exposure to adverse environments.

PMID- 29212879
TI  - Single-molecule measurements of the effect of force on Thy-1/alphavbeta3-integrin
      interaction using nonpurified proteins.
AB  - Thy-1 and alphavbeta3 integrin mediate bidirectional cell-to-cell communication
      between neurons and astrocytes. Thy-1/alphavbeta3 interactions stimulate
      astrocyte migration and the retraction of neuronal prolongations, both processes
      in which internal forces are generated affecting the bimolecular interactions
      that maintain cell-cell adhesion. Nonetheless, how the Thy-1/alphavbeta3
      interactions respond to mechanical cues is an unresolved issue. In this study,
      optical tweezers were used as a single-molecule force transducer, and the Dudko
      Hummer-Szabo model was applied to calculate the kinetic parameters of Thy
      1/alphavbeta3 dissociation. A novel experimental strategy was implemented to
      analyze the interaction of Thy-1-Fc with nonpurified alphavbeta3-Fc integrin,
      whereby nonspecific rupture events were corrected by using a new mathematical
      approach. This methodology permitted accurately estimating specific rupture
      forces for Thy-1-Fc/alphavbeta3-Fc dissociation and calculating the kinetic and
      transition state parameters. Force exponentially accelerated Thy-1/alphavbeta3
      dissociation, indicating slip bond behavior. Importantly, nonspecific
      interactions were detected even for purified proteins, highlighting the
      importance of correcting for such interactions. In conclusion, we describe a new
      strategy to characterize the response of bimolecular interactions to forces even
      in the presence of nonspecific binding events. By defining how force regulates
      Thy-1/alphavbeta3 integrin binding, we provide an initial step towards
      understanding how the neuron-astrocyte pair senses and responds to mechanical
      cues.

PMID- 29212881
TI  - Risk of Rotavirus Nosocomial Spread After Inpatient Pentavalent Rotavirus
      Vaccination.
AB  - BACKGROUND: Infants born prematurely or with underlying conditions are at
      increased risk of severe rotavirus disease and associated complications. Given
      the theoretical risk of nosocomial transmission of vaccine-type rotavirus,
      rotavirus vaccination is recommended for infants at or after discharge from
      neonatal care settings. Because the first dose should be administered by 104 days
      of age, some infants may be age-ineligible for vaccination if delayed until
      discharge. METHODS: This prospective cohort included infants admitted to an urban
      academic medical center between birth and 104 days who received care in intensive
      care settings. Pentavalent human-bovine reassortant rotavirus vaccine (RV5) was
      used, per routine clinical care. Stool specimens were collected weekly (February
      2013-April 2014) and analyzed for rotavirus strains using real-time reverse
      transcription-polymerase chain reaction. Demographic and vaccine data were
      collected. RV5 safety was not assessed. RESULTS: Of 385 study infants, 127 were
      age-eligible for routine vaccinations during hospitalization. At discharge, 32.7%
      were up-to-date for rotavirus vaccination, compared with 82.7% for other
      vaccinations. Of rotavirus-unvaccinated infants, 42.6% were discharged at age
      >104 days and thus vaccination-ineligible. Of 1192 stool specimens collected,
      rotavirus was detected in 13 (1.1%): 1 wild-type strain from an unvaccinated
      infant; 12 vaccine-type strains from 9 RV5-vaccinated infants. No vaccine-type
      rotavirus cases were observed among unvaccinated infants (incidence rate: 0.0
      [95% confidence interval: 0.0-1.5] cases per 1000 patient days at risk).
      CONCLUSIONS: These data suggest that delaying rotavirus vaccination until
      discharge from the hospital could lead to missed vaccination opportunities and
      may be unnecessary in institutions using RV5 with comparable infection control
      standards.

PMID- 29212882
TI  - Rotavirus Immunization for Hospitalized Infants: Are We There Yet?

PMID- 29212883
TI  - Half a Century of IUPS.

PMID- 29212884
TI  - Return Physiology to Center Stage: Some Personal Thoughts.

PMID- 29212885
TI  - Global Status of Physiology in Research, Education, and Outreach.

PMID- 29212886
TI  - Lactate, not Lactic Acid, is Produced by Cellular Cytosolic Energy Catabolism.

PMID- 29212887
TI  - Reply to Robergs et al.

PMID- 29212888
TI  - Physiology in Perspective: Stem Cells and Regenerative Physiology.

PMID- 29212889
TI  - Stem Cell Differentiation is Regulated by Extracellular Matrix Mechanics.
AB  - Stem cells mechanosense the stiffness of their microenvironment, which impacts
      differentiation. Although tissue hydration anti-correlates with stiffness,
      extracellular matrix (ECM) stiffness is clearly transduced into gene expression
      via adhesion and cytoskeleton proteins that tune fates. Cytoskeletal
      reorganization of ECM can create heterogeneity and influence fates, with fibrosis
      being one extreme.

PMID- 29212892
TI  - The Underlying Genetics of Drosophila Circadian Behaviors.
AB  - Life is shaped by circadian clocks. This review focuses on how behavioral
      genetics in the fruit fly unveiled what is known today about circadian
      physiology. We will briefly summarize basic properties of the clock and focus on
      some clock-controlled behaviors to highlight how communication between central
      and peripheral oscillators defines their properties.

PMID- 29212891
TI  - Bypassing Border Control: Nuclear Envelope Rupture in Disease.
AB  - Recent observations in laminopathy patient cells and cancer cells have revealed
      that the nuclear envelope (NE) can transiently rupture during interphase. NE
      rupture leads to an uncoordinated exchange of nuclear and cytoplasmic material,
      thereby deregulating cellular homeostasis. Moreover, concurrently inflicted DNA
      damage could prime rupture-prone cells for genome instability. Thus, NE rupture
      may represent a novel pathogenic mechanism that has far-reaching consequences for
      cell and organism physiology.

PMID- 29212893
TI  - Comparative Physiology of Nociception and Pain.
AB  - The study of diverse animal groups allows us to discern the evolution of the
      neurobiology of nociception. Nociception functions as an important alarm system
      alerting the individual to potential and actual tissue damage. All animals
      possess nociceptors, and, in some animal groups, it has been demonstrated that
      there are consistent physiological mechanisms underpinning the nociceptive
      system. This review considers the comparative biology of nociception and pain
      from an evolutionary perspective.

PMID- 29212890
TI  - Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size
      Regulation.
AB  - Recent loss-of-function studies show that satellite cell depletion does not
      promote sarcopenia or unloading-induced atrophy, and does not prevent regrowth.
      Although overload-induced muscle fiber hypertrophy is normally associated with
      satellite cell-mediated myonuclear accretion, hypertrophic adaptation proceeds in
      the absence of satellite cells in fully grown adult mice, but not in young
      growing mice. Emerging evidence also indicates that satellite cells play an
      important role in remodeling the extracellular matrix during hypertrophy.

PMID- 29212894
TI  - HIV and Cardiovascular Disease: Role of Immunometabolic Perturbations.
AB  - The successful rollout of anti-retroviral therapy ensured that HIV is
      increasingly managed as a chronic condition. HIV-positive persons are therefore
      exhibiting increased cardiovascular complications. This review focuses on the
      emerging role of "immunometabolism" within the context of HIV-related immune
      dysregulation and cardiovascular disease onset. Here, persistent immune
      activation contributes to pathophysiological perturbations during early
      infection, resulting in immune cell metabolic reprogramming and the activation of
      coagulation pathways in HIV-positive individuals.

PMID- 29212895
TI  - Functional Metabolomics Characterizes a Key Role for N-Acetylneuraminic Acid in
      Coronary Artery Diseases.
AB  - BACKGROUND: As new biomarkers of coronary artery diseases (CAD) emerge via
      metabolomics, the underlying functional mechanisms remain to be elucidated.
      Functional metabolomics aims to translate metabolomics-derived biomarkers to
      disease mechanisms. METHODS: A cohort of 2324 patients who underwent coronary
      angiography from 4 independent centers was studied. A combination of ultra
      performance liquid chromatography and quadrupole time-of-flight mass spectrometry
      in the negative ion mode was used for untargeted analysis of metabolites in
      plasma. Significant differential metabolites were identified by cross-comparisons
      with and within CAD types, including normal coronary artery, nonobstructvie
      coronary atherosclerosis, stable angina, unstable angina, and acute myocardial
      infarction. A tandem liquid chromatography-mass spectrometry-based approach using
      isotope-labeled standard addition was subsequently performed for targeted
      analysis of the metabolic marker N-acetylneuraminic acid (Neu5Ac). A functional
      metabolomics strategy was proposed to investigate the role of Neu5Ac in the
      progression of CAD by using in vitro and in vivo models. RESULTS: We identified a
      total of 36 differential metabolites, 35 of which were confirmed with reference
      compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in
      center 1 (P=4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The
      increased level of Neu5Ac in plasma was confirmed by accurate targeted
      quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in
      vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing
      protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1.
      Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation,
      ameliorated oxygen-glucose deprivation-induced injury in cardiomyocytes and
      ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological
      inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir,
      also protected cardiomyocytes and the heart from myocardial injury. CONCLUSIONS:
      Functional metabolomics identified a key role for Neu5Ac in acute myocardial
      infarction, and targeting neuraminidase-1 may represent an unrecognized
      therapeutic intervention for CAD.

PMID- 29212896
TI  - Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell
      Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular
      Cardiomyopathy/Dysplasia.
AB  - BACKGROUND: Desmin (DES) mutations cause severe skeletal and cardiac muscle
      disease with heterogeneous phenotypes. Recently, DES mutations were described in
      patients with inherited arrhythmogenic right ventricular
      cardiomyopathy/dysplasia, although their cellular and molecular pathomechanisms
      are not precisely known. Our aim is to describe clinically and functionally the
      novel DES-p.Glu401Asp mutation as a cause of inherited left ventricular
      arrhythmogenic cardiomyopathy/dysplasia. METHODS: We identified the novel DES
      mutation p.Glu401Asp in a large Spanish family with inherited left ventricular
      arrhythmogenic cardiomyopathy/dysplasia and a high incidence of adverse cardiac
      events. A full clinical evaluation was performed on all mutation carriers and
      noncarriers to establish clinical and genetic cosegregation. In addition, desmin,
      and intercalar disc-related proteins expression were histologically analyzed in
      explanted cardiac tissue affected by the DES mutation. Furthermore, mesenchymal
      stem cells were isolated and cultured from 2 family members with the DES mutation
      (1 with mild and 1 with severe symptomatology) and a member without the mutation
      (control) and differentiated ex vivo to cardiomyocytes. Then, important genes
      related to cardiac differentiation and function were analyzed by real-time
      quantitative polymerase chain reaction. Finally, the p.Glu401Asp mutated DES gene
      was transfected into cell lines and analyzed by confocal microscopy. RESULTS: Of
      the 66 family members screened for the DES-p.Glu401Asp mutation, 23 of them were
      positive, 6 were obligate carriers, and 2 were likely carriers. One hundred
      percent of genotype-positive patients presented data consistent with inherited
      arrhythmogenic cardiomyopathy/dysplasia phenotype with variable disease severity
      expression, high-incidence of sudden cardiac death, and absence of skeletal
      myopathy or conduction system disorders. Immunohistochemistry was compatible with
      inherited arrhythmogenic cardiomyopathy/dysplasia, and the functional study
      showed an abnormal growth pattern and cellular adhesion, reduced desmin RNA
      expression, and some other membrane proteins, as well, and desmin aggregates in
      transfected cells expressing the mutant desmin. CONCLUSIONS: The DES-p.Glu401Asp
      mutation causes predominant inherited left ventricular arrhythmogenic
      cardiomyopathy/dysplasia with a high incidence of adverse clinical events in the
      absence of skeletal myopathy or conduction system disorders. The pathogenic
      mechanism probably corresponds to an alteration in desmin dimer and oligomer
      assembly and its connection with membrane proteins within the intercalated disc.

PMID- 29212897
TI  - Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels
      and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis.
AB  - BACKGROUND: Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme
      expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP
      8 are associated with the risk for and outcome of cardiovascular diseases (CVDs).
      The origin of circulating MMP-8 is not completely clear. METHODS AND RESULTS: We
      performed a genome-wide association study of serum MMP-8 levels in 2 populations
      comprising altogether 6049 individuals. Moreover, we studied whether MMP-8
      associated variants are linked to increased risk of CVDs and overall mortality in
      >20 000 subjects. The strongest association with serum MMP-8 was found in locus
      1q31.3, containing the gene for complement factor H (lead single nucleotide
      polymorphism: rs800292; P=2.4*10-35). In functional experiments, activation of
      the alternative pathway of complement in the carriers of rs800292 minor allele
      (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared
      with the major allele (Val62 in factor H). Another association was detected in
      1q21.3, containing genes S100A8, S100A9, and S100A12 (strongest association:
      rs1560833; P=5.3*10-15). The minor allele of rs1560833 was inversely associated
      with CVD (odds ratio [95% confidence interval]: 0.90 [0.82-0.99]; P=0.032) and
      the time to incident CVD event (hazard ratio [95% confidence interval]: 0.91
      [0.84-0.99]; P=0.032) in men but not in women. CONCLUSIONS: According to our
      results, the activation of the alternative pathway of the complement system
      strongly contributes to serum MMP-8 concentration. Genetic polymorphism in S100A9
      S100A12-S100A8 locus affects serum and plasma MMP-8 and shows a suggestive
      association with the risk of CVDs. Our results show that genetic variation
      determines a significant portion of circulating MMP-8 concentrations.

PMID- 29212898
TI  - Genetic Testing in Pediatric Left Ventricular Noncompaction.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) can occur in isolation or can
      co-occur with a cardiomyopathy phenotype or cardiovascular malformation. The
      yield of cardiomyopathy gene panel testing in infants, children, and adolescents
      with a diagnosis of LVNC is unknown. By characterizing a pediatric population
      with LVNC, we sought to determine the yield of cardiomyopathy gene panel testing,
      distinguish the yield of testing for LVNC with or without co-occurring cardiac
      findings, and define additional factors influencing genetic testing yield.
      METHODS AND RESULTS: One hundred twenty-eight individuals diagnosed with LVNC at
      <=21 years of age were identified, including 59% with idiopathic pathogenesis,
      32% with familial disease, and 9% with a syndromic or metabolic diagnosis.
      Overall, 75 individuals had either cardiomyopathy gene panel (n=65) or known
      variant testing (n=10). The yield of cardiomyopathy gene panel testing was 9%.
      The severity of LVNC by imaging criteria was not associated with positive genetic
      testing, co-occurring cardiac features, pathogenesis, family history, or
      myocardial dysfunction. Individuals with isolated LVNC were significantly less
      likely to have a positive genetic testing result compared with those with LVNC
      and co-occurring cardiomyopathy (0% versus 12%, respectively; P<0.01).
      CONCLUSIONS: Genetic testing should be considered in individuals with
      cardiomyopathy co-occurring with LVNC. These data do not suggest an indication
      for cardiomyopathy gene panel testing in individuals with isolated LVNC in the
      absence of a family history of cardiomyopathy.

PMID- 29212901
TI  - FLNC (Filamin-C): A New(er) Player in the Field of Genetic Cardiomyopathies.

PMID- 29212899
TI  - Novel Mutation in FLNC (Filamin C) Causes Familial Restrictive Cardiomyopathy.
AB  - BACKGROUND: Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy
      characterized by impaired diastolic ventricular function resulting in a poor
      clinical prognosis. Rarely, heritable forms of RCM have been reported, and
      mutations underlying RCM have been identified in genes that govern the
      contractile function of the cardiomyocytes. METHODS AND RESULTS: We evaluated 8
      family members across 4 generations by history, physical examination,
      electrocardiography, and echocardiography. Affected individuals presented with a
      pleitropic syndrome of progressive RCM, atrioventricular septal defects, and a
      high prevalence of atrial fibrillation. Exome sequencing of 5 affected members
      identified a single novel missense variant in a highly conserved residue of FLNC
      (filamin C; p.V2297M). FLNC encodes filamin C-a protein that acts as both a
      scaffold for the assembly and organization of the central contractile unit of
      striated muscle and also as a mechanosensitive signaling molecule during cell
      migration and shear stress. Immunohistochemical analysis of FLNC localization in
      cardiac tissue from an affected family member revealed a diminished localization
      at the z disk, whereas traditional localization at the intercalated disk was
      preserved. Stem cell-derived cardiomyocytes mutated to carry the effect allele
      had diminished contractile activity when compared with controls. CONCLUSION: We
      have identified a novel variant in FLNC as pathogenic variant for familial RCM-a
      finding that further expands on the genetic basis of this rare and morbid
      cardiomyopathy.

PMID- 29212902
TI  - Is Left Ventricular Noncompaction a Trait, Phenotype, or Disease? The Evidence
      Points to Phenotype.

PMID- 29212900
TI  - Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt
      Study (Genetic Epidemiology Network of Salt Sensitivity).
AB  - BACKGROUND: Gene-environmental interaction analysis can identify novel genetic
      factors for blood pressure (BP). We performed genome-wide analyses to identify
      genomic loci that interact with potassium to influence BP using single-marker (1
      and 2 df joint tests) and gene-based tests among Chinese participants of the
      GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). METHODS AND
      RESULTS: Among 1876 GenSalt participants, the average of 3 urine samples was used
      to estimate potassium excretion. Nine BP measurements were taken using a random
      zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms
      were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing
      and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00*10-4)
      from GenSalt were evaluated for replication among 775 Chinese participants of the
      MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and
      gene-based results were meta-analyzed across the GenSalt and MESA studies to
      determine genome-wide significance. The 1 df tests identified interactions for
      ARL15 rs16882447 on systolic BP (P=2.83*10-9) and RANBP3L rs958929 on pulse
      pressure (P=1.58*10-8). The 2 df tests confirmed the ARL15 rs16882447 signal for
      systolic BP (P=1.15*10-9). Genome-wide gene-based analysis identified CC2D2A
      (P=2.59*10-7) at 4p15.32 and BNC2 (P=4.49*10-10) at 9p22.2 for systolic BP,
      GGNBP1 (P=1.18*10-8), and LINC00336 (P=1.36*10-8) at 6p21 for diastolic BP, DAB1
      (P=1.05*10-13) at 1p32.2, and MIR4466 (P=5.34*10-8) at 6q25.3 for pulse pressure.
      The BNC2 (P=3.57*10-8) gene was also significant for mean arterial pressure.
      CONCLUSIONS: We identified 2 novel BP loci and 6 genes through the examination of
      single nucleotide polymorphism- and gene-based interactions with potassium.

PMID- 29212903
TI  - Cardiovascular Risk and Matrix Metalloproteinase Polymorphisms: Not Just a Simple
      Substitution.

PMID- 29212904
TI  - Dendritic Cell RIPK1 Maintains Immune Homeostasis by Preventing Inflammation and
      Autoimmunity.
AB  - Necroptosis is a form of cell death associated with inflammation; however, the
      biological consequences of chronic necroptosis are unknown. Necroptosis is
      mediated by RIPK1, RIPK3, and MLKL kinases but in hematopoietic cells RIPK1 has
      anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate
      the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1
      in mouse dendritic cells. We demonstrate that deregulated necroptosis results in
      systemic inflammation, tissue fibrosis, and autoimmunity. We show that
      inflammation and autoimmunity are prevented upon expression of kinase inactive
      RIPK1 or deletion of RIPK3 or MLKL. We provide evidence that the inflammation is
      not driven by microbial ligands, but depends on the release of danger-associated
      molecular patterns and MyD88-dependent signaling. Importantly, although the
      inflammation is independent of type I IFN and the nucleic acid sensing TLRs,
      blocking these pathways rescues the autoimmunity. These mouse genetic studies
      reveal that chronic necroptosis may underlie human fibrotic and autoimmune
      disorders.

PMID- 29212905
TI  - Cyclic GMP-AMP Synthase Is the Cytosolic Sensor of Plasmodium falciparum Genomic
      DNA and Activates Type I IFN in Malaria.
AB  - Innate immune receptors have a key role in the sensing of malaria and initiating
      immune responses. As a consequence of infection, systemic inflammation emerges
      and is directly related to signs and symptoms during acute disease. We have
      previously reported that plasmodial DNA is the primary driver of systemic
      inflammation in malaria, both within the phagolysosome and in the cytosol of
      effector cells. In this article, we demonstrate that Plasmodium falciparum
      genomic DNA delivered to the cytosol of human monocytes binds and activates
      cyclic GMP-AMP synthase (cGAS). Activated cGAS synthesizes 2'3'-cGAMP, which we
      subsequently can detect using liquid chromatography-tandem mass spectrometry.
      2'3'-cGAMP acts as a second messenger for STING activation and triggers TBK1/IRF3
      activation, resulting in type I IFN production in human cells. This induction of
      type I IFN was independent of IFI16. Access of DNA to the cytosolic compartment
      is mediated by hemozoin, because incubation of purified malaria pigment with
      DNase abrogated IFN-beta induction. Collectively, these observations implicate
      cGAS as an important cytosolic sensor of P. falciparum genomic DNA and reveal the
      role of the cGAS/STING pathway in the induction of type I IFN in response to
      malaria parasites.

PMID- 29212906
TI  - Osteoblasts Are Rapidly Ablated by Virus-Induced Systemic Inflammation following
      Lymphocytic Choriomeningitis Virus or Pneumonia Virus of Mice Infection in Mice.
AB  - A link between inflammatory disease and bone loss is now recognized. However,
      limited data exist on the impact of virus infection on bone loss and
      regeneration. Bone loss results from an imbalance in remodeling, the
      physiological process whereby the skeleton undergoes continual cycles of
      formation and resorption. The specific molecular and cellular mechanisms linking
      virus-induced inflammation to bone loss remain unclear. In the current study, we
      provide evidence that infection of mice with either lymphocytic choriomeningitis
      virus (LCMV) or pneumonia virus of mice (PVM) resulted in rapid and substantial
      loss of osteoblasts from the bone surface. Osteoblast ablation was associated
      with elevated levels of circulating inflammatory cytokines, including TNF-alpha,
      IFN-gamma, IL-6, and CCL2. Both LCMV and PVM infections resulted in reduced
      osteoblast-specific gene expression in bone, loss of osteoblasts, and reduced
      serum markers of bone formation, including osteocalcin and procollagen type 1 N
      propeptide. Infection of Rag-1-deficient mice (which lack adaptive immune cells)
      or specific depletion of CD8+ T lymphocytes limited osteoblast loss associated
      with LCMV infection. By contrast, CD8+ T cell depletion had no apparent impact on
      osteoblast ablation in association with PVM infection. In summary, our data
      demonstrate dramatic loss of osteoblasts in response to virus infection and
      associated systemic inflammation. Further, the inflammatory mechanisms mediating
      viral infection-induced bone loss depend on the specific inflammatory condition.

PMID- 29212907
TI  - Role of the EHD Family of Endocytic Recycling Regulators for TCR Recycling and T
      Cell Function.
AB  - T cells use the endocytic pathway for key cell biological functions, including
      receptor turnover and maintenance of the immunological synapse. Some of the
      established players include the Rab GTPases, the SNARE complex proteins, and
      others, which function together with EPS-15 homology domain-containing (EHD)
      proteins in non-T cell systems. To date, the role of the EHD protein family in T
      cell function remains unexplored. We generated conditional EHD1/3/4 knockout mice
      using CD4-Cre and crossed these with mice bearing a myelin oligodendrocyte
      glycoprotein-specific TCR transgene. We found that CD4+ T cells from these mice
      exhibited reduced Ag-driven proliferation and IL-2 secretion in vitro. In vivo,
      these mice exhibited reduced severity of experimental autoimmune
      encephalomyelitis. Further analyses showed that recycling of the TCR-CD3 complex
      was impaired, leading to increased lysosomal targeting and reduced surface levels
      on CD4+ T cells of EHD1/3/4 knockout mice. Our studies reveal a novel role of the
      EHD family of endocytic recycling regulatory proteins in TCR-mediated T cell
      functions.

PMID- 29212908
TI  - Naive CD4+ T Cells Carrying a TLR2 Agonist Overcome TGF-beta-Mediated Tumor
      Immune Evasion.
AB  - TLR agonists are effective at treating superficial cancerous lesions, but their
      use internally for other types of tumors remains challenging because of toxicity.
      In this article, we report that murine and human naive CD4+ T cells that
      sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3
      cells encoding the OVA-specific TCR OT2, when transferred into mice bearing
      established TGF-beta-OVA-expressing thymomas, produce high amounts of IFN-gamma
      and sensitize tumors to PD-1/programmed cell death ligand 1 blockade-induced
      rejection. In contrast, naive OT2 cells without Pam3Cys4 cargo are prone to TGF
      beta-dependent inducible regulatory Foxp3+ CD4+ T cell conversion and accelerate
      tumor growth that is largely unaffected by PD-1/programmed cell death ligand 1
      blockade. Ex vivo analysis reveals that CD4+ TPam3 cells are resistant to TGF
      beta-mediated gene expression through Akt activation controlled by inputs from
      the TCR and a TLR2-MyD88-dependent PI3K signaling pathway. These data show that
      CD4+ TPam3 cells are capable of Th1 differentiation in the presence of TGF-beta,
      suggesting a novel approach to adoptive cell therapy.

PMID- 29212909
TI  - PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host
      Disease.
AB  - Effector memory T cells (TEM) are less capable of inducing graft-versus-host
      disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR
      transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor
      histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found
      that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to
      TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did
      TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD
      because of increased sensitivity to PD-ligands. In this study, we tested this
      hypothesis and found that indeed TS1 TEM induced more severe skin and liver GVHD
      in the absence of PD-ligands. However, lack of PD-ligands did not result in early
      weight loss and colon GVHD comparable to that induced by TS1 TN, indicating that
      additional pathways restrain alloreactive TEM TS1 TN also caused more severe GVHD
      without PD-ligands. The absence of PD-ligands on donor bone marrow was sufficient
      to augment GVHD caused by either TEM or TN, indicating that donor PD-ligand
      expressing APCs critically regulate GVHD. In the absence of PD-ligands, both TS1
      TEM and TN induced late-onset myocarditis. Surprisingly, this was an autoimmune
      manifestation, because its development required non-TS1 polyclonal CD8+ T cells.
      Myocarditis development also required donor bone marrow to be PD-ligand
      deficient, demonstrating the importance of donor APC regulatory function. In
      summary, PD-ligands suppress both miHA-directed GVHD and the development of
      alloimmunity-induced autoimmunity after allogeneic hematopoietic transplantation.

PMID- 29212911
TI  - A Role of NKR-P1A (CD161) and Lectin-like Transcript 1 in Natural Cytotoxicity
      against Human Articular Chondrocytes.
AB  - Normal cartilage cells are susceptible to lysis by NK cells. This phenomenon may
      play a role in immune cartilage destruction; however, the mechanisms of
      chondrocyte recognition by NK cells remain poorly understood. Therefore, the aim
      of this study was to reveal a possible role of NKR-P1A/lectin-like transcript 1
      (LLT1) interaction in NK cell-mediated cytotoxicity against normal human
      articular chondrocytes. Chondrocytes were isolated from articular cartilage
      obtained during talonavicular joint surgery. PBMC or polyclonal NK cells isolated
      from normal donors served as effector cells. Cell-mediated cytotoxicity against
      chondrocytes was evaluated by means of 18-h 51Cr-release assay. Specific mRNA
      expression was evaluated by classical and quantitative RT-PCR, and proteins were
      detected by Western blot analysis. We found that lysis of articular chondrocytes
      by PBMC or polyclonal NK cells was potentiated by stimulation with IL-2.
      Stimulation of effector cells with IL-2 downregulated mRNA expression of
      inhibitory NKR-P1A NK cell receptor, and blocking of NKR-P1A with specific mAbs
      resulted in increased chondrocyte killing. Chondrocytes constitutively expressed
      LLT1, a ligand of NKR-P1A. LLT1 expression by chondrocytes could be upregulated
      by IL-1alpha and TNF. Chondrocyte treatment with IL-1alpha resulted in their
      increased resistance to killing by natural cytotoxic cells. This could be
      reversed by blocking of NKR-P1A. These results show that susceptibility of normal
      articular chondrocytes to lysis by NK cells is modulated by NKR-P1A/LLT1
      interactions. Thus, NKR-P1A/LLT1 interaction might provide some novel target for
      therapeutic interventions in the course of pathological cartilage injury.

PMID- 29212910
TI  - Foxp1 Negatively Regulates T Follicular Helper Cell Differentiation and Germinal
      Center Responses by Controlling Cell Migration and CTLA-4.
AB  - T follicular helper (Tfh) cells play an essential role in the formation of
      germinal centers (GC) and generation of high-affinity Abs. The homing of
      activated CD4+ T cells into B cell follicles and the involvement of key
      costimulatory and coinhibitory molecules are critical in controlling both the
      initiation and the magnitude of GC responses. Meanwhile, studies have shown that
      a high number of single clone B cells leads to intraclonal competition, which
      inhibits the generation of high-affinity Abs. Our previous work has shown that
      transcription factor Foxp1 is a critical negative regulator of Tfh cell
      differentiation. In this study, we report that the deletion of Foxp1 leads to a
      high proportion of activated CD4+ T cells homing into B cell follicles with
      faster kinetics, resulting in earlier GC formation. In addition, we show that
      Foxp1-deficient Tfh cells restore the generation of high-affinity Abs when
      cotransferred with high numbers of single clone B cells. We find that Foxp1
      regulates the expression levels of cytotoxic T lymphocyte-associated Ag-4 (CTLA
      4) in activated CD4+ T cells and that Ctla4 is a direct Foxp1 target. Finally, we
      demonstrate that CTLA-4 expression on conventional CD4+ T cells plays a cell
      intrinsic role in Tfh cell differentiation in vivo, and CTLA-4 blockade helps
      abolish the intraclonal competition of B cells in generating high-affinity Abs.

PMID- 29212912
TI  - Effect of Saccharomyces boulardii in dog with chronic enteropathies: double
      blinded, placebo-controlled study.
AB  - Saccharomyces boulardii is used to treat acute and chronic enteropathies in
      humans, but to date, no studies have evaluated the use of this yeast in dogs. The
      current study, a prospective non-randomised, double-blinded, placebo-controlled
      study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic
      enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In
      healthy dogs, S boulardii was administered for 10 days. Possible short-term
      adverse effects were recorded, and quantitative stool cultures for yeasts were
      performed. In dogs with CE, S boulardii or a placebo was administered in addition
      to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity
      Index, abdominal ultrasonography, gastroenteroscopy and histology were performed
      at the time of diagnosis and after 60 days of treatment. In healthy dogs, S
      boulardii reached a steady state in five days and was completely eliminated on
      day 4 after administration. No short-term side effects were seen. Clinical
      activity index, stool frequency, stool consistency and body condition score
      improved significantly in dogs with CE receiving S boulardii versus the placebo.
      In conclusion, S boulardii can be safely used in dogs with CE and seems to
      achieve better control of clinical signs than standard therapy alone.

PMID- 29212913
TI  - Molecular characterisation of Mycobacterium caprae strains isolated in Poland.
AB  - Bovine tuberculosis (bovine TB, bTB) is caused by bovine bacilli: Mycobacterium
      bovis and M caprae The studies conducted in Poland, in the National Bovine
      Tuberculosis Reference Laboratory in the Department of Microbiology of the
      National Veterinary Research Institute in Pulawy, show that animal tuberculosis
      in Poland is also caused by M caprae We here describe the identification and
      genotypic assessment of 52 isolates of M caprae obtained from Polish cattle and
      wild animals over the last five years. We show that strains isolated from bison
      have significant genotypic diversity and are distinct compared with the genotypes
      of strains isolated from cattle. Similarly, isolates from cattle herds can be
      highly genotypically variable. Formal designation of the members of the
      Mycobacterium tuberculosis complex is controversial in Poland; there is a gap in
      veterinary legislation with regard to bTB and no explicit mention of M caprae
      causing tuberculosis in animal.

PMID- 29212915
TI  - Altered synaptic transmission and maturation of hippocampal CA1 neurons in a
      mouse model of human chr16p11.2 microdeletion.
AB  - The pathophysiology of neurodevelopmental disorders is often observed early in
      infancy and toddlerhood. Mouse models of syndromic disorders have provided
      insight regarding mechanisms of action, but most studies have focused on
      characterization in juveniles and adults. Insight into developmental
      trajectories, particularly those related to circuit and synaptic function, will
      likely yield important information regarding disorder pathogenesis that leads to
      symptom progression. Chromosome 16p11.2 microdeletion is one of the most common
      copy number variations associated with a spectrum of neurodevelopmental
      disorders. Yet, how haploinsufficiency of chr16p11.2 affects early synaptic
      maturation and function is unknown. To address this knowledge gap, the present
      study focused on three key components of circuit formation and function, basal
      synaptic transmission, local circuit function, and maturation of glutamatergic
      synapses, in developing hippocampal CA1 neurons in a chr16p11.2 microdeletion
      mouse model. The data demonstrate increased excitability, imbalance in excitation
      and inhibition, and accelerated maturation of glutamatergic synapses in
      heterozygous deletion mutant CA1 neurons. Given the critical role of early
      synaptic development in shaping neuronal connectivity and circuitry formation,
      these newly identified synaptic abnormalities in chr16p11.2 microdeletion mice
      may contribute to altered developmental trajectory and function of the developing
      brain. NEW & NOTEWORTHY The synaptic pathophysiology underlying
      neurodevelopmental disorders often emerges during infancy and toddlerhood.
      Therefore, identifying initial changes in synaptic function is crucial for
      gaining a mechanistic understanding of the pathophysiology, which ultimately will
      facilitate the design of early interventions. Here, we investigated synaptic and
      local circuit properties of hippocampal CA1 neurons in a human chr16p11.2
      microdeletion mouse model during early postnatal development (preweaning). The
      data demonstrate increased neuronal excitability, excitatory/inhibitory
      imbalance, and accelerated maturation of glutamatergic synapses. These
      perturbations in early hippocampal circuit function may underlie the early
      pathogenesis of the heterozygous chr16p11.2 microdeletion, which is often
      associated with epilepsy and intellectual disability.

PMID- 29212916
TI  - Task dependence of odor discrimination: choosing between speed and accuracy.
AB  - Odor discrimination is a complex task that may be improved by increasing sampling
      time to facilitate evidence accumulation. However, experiments testing this
      phenomenon in olfaction have produced conflicting results. To resolve this
      disparity, Frederick et al. (Frederick DE, Brown A, Tacopina S, Mehta N, Vujovic
      M, Brim E, Amina T, Fixsen B, Kay LM. J Neurosci 37: 4416-4426, 2017) conducted
      experiments that suggest that sampling time and performance are task dependent.
      Their findings have implications for understanding olfactory processing and
      experimental design, specifically the effect of subtle differences in
      experimental design on study results.

PMID- 29212914
TI  - Distributed force feedback in the spinal cord and the regulation of limb
      mechanics.
AB  - This review is an update on the role of force feedback from Golgi tendon organs
      in the regulation of limb mechanics during voluntary movement. Current ideas
      about the role of force feedback are based on modular circuits linking idealized
      systems of agonists, synergists, and antagonistic muscles. In contrast, force
      feedback is widely distributed across the muscles of a limb and cannot be
      understood based on these circuit motifs. Similarly, muscle architecture cannot
      be understood in terms of idealized systems, since muscles cross multiple joints
      and axes of rotation and further influence remote joints through inertial
      coupling. It is hypothesized that distributed force feedback better represents
      the complex mechanical interactions of muscles, including the stresses in the
      musculoskeletal network born by muscle articulations, myofascial force
      transmission, and inertial coupling. Together with the strains of muscle
      fascicles measured by length feedback from muscle spindle receptors, this
      integrated proprioceptive feedback represents the mechanical state of the
      musculoskeletal system. Within the spinal cord, force feedback has excitatory and
      inhibitory components that coexist in various combinations based on motor task
      and integrated with length feedback at the premotoneuronal and motoneuronal
      levels. It is concluded that, in agreement with other investigators, autogenic,
      excitatory force feedback contributes to propulsion and weight support. It is
      further concluded that coexistent inhibitory force feedback, together with length
      feedback, functions to manage interjoint coordination and the mechanical
      properties of the limb in the face of destabilizing inertial forces and positive
      force feedback, as required by the accelerations and changing directions of both
      predator and prey.

PMID- 29212918
TI  - The influence of vertical disparity gradient and cue conflict on EEG omega
      complexity in Panum's limiting case.
AB  - Using behavioral measures and ERP technique, researchers discovered at least two
      factors could influence the final perception of depth in Panum's limiting case,
      which are the vertical disparity gradient and the degree of cue conflict between
      two- and three-dimensional shapes. Although certain event-related potential
      components have been proved to be sensitive to the different levels of these two
      factors, some methodological limitations existed in this technique. In this
      study, we proposed that the omega complexity of EEG signal may serve as an
      important supplement of the traditional event-related potential technique. We
      found that the trials with lower vertical gradient disparity have lower omega
      complexity (i.e., higher global functional connectivity) of the occipital region,
      especially that of the right-occipital hemisphere. Moreover, for occipital omega
      complexity, the trials with low-cue conflict have significantly larger omega
      complexity than those with medium- and high-cue conflict. It is also found that
      the electrodes located in the middle line of the occipital region (i.e., POz and
      Oz) are more crucial to the impact of different levels of cue conflict on omega
      complexity than the other electrodes located in the left- and right-occipital
      hemispheres. These evidences demonstrated that the EEG omega complexity could
      reflect distinct neural activities evoked by Panum's limiting case
      configurations, with different levels of vertical disparity gradient and cue
      conflict. Besides, the influence of vertical disparity gradient and cue conflict
      on omega complexity may be regional dependent. NEW & NOTEWORTHY The EEG omega
      complexity could reflect distinct neural activities evoked by Panum's limiting
      case configurations with different levels of vertical disparity gradient and cue
      conflict. The influence of vertical disparity gradient and cue conflict on omega
      complexity is regional dependent. The omega complexity of EEG signal can serve as
      an important supplement of the traditional ERP technique.

PMID- 29212919
TI  - Neuronal dynamics supporting formation and recombination of cross-modal olfactory
      tactile association in the rat hippocampal formation.
AB  - The present study is aimed at describing some aspects of the neural dynamics
      supporting discrimination of olfactory-tactile paired-associated stimuli during
      acquisition of new pairs and during recombination of previously learned pairs in
      the rat. To solve the task, animals have to identify one odor-texture (OT)
      combination associated with a food reward among three cups with overlapping
      elements. Previous experiments demonstrated that the lateral entorhinal cortex
      (LEC) is involved in the processes underlying OT acquisition, whereas the dorsal
      hippocampus (DH) is selectively involved in the recombination processes. In the
      present study, local field potentials were recorded form the anterior piriform
      cortex (aPC), LEC, and DH in freely moving rats performing these tasks. Signal
      analysis focused on theta (5-12 Hz)- and beta-band (15-40 Hz) oscillatory
      activities in terms of both amplitude and synchrony. The results show that cue
      sampling was associated with a significant increase in the beta-band activity
      during the choice period in both the aPC and the LEC, and is modulated by level
      of expertise and the animal's decision. In addition, this increase was
      significantly higher during the recombination compared with the acquisition of
      the OT task, specifically when animals had to neglect the odor previously
      associated with the reward. Finally, a significant decrease in coherence in the
      theta band between LEC and DH was observed in the recombination but not in the
      acquisition task. These data point to specific neural signatures of simple and
      complex cross-modal sensory processing in the LEC-DH complex. NEW & NOTEWORTHY
      This study is the first to describe electrophysiological correlates of cross
      modal olfactory-tactile integration in rats. Recordings were sought from the
      lateral entorhinal cortex and the dorsal hippocampus because previous studies
      have shown their role in the formation and in the recombination of previously
      learned associations. We identified specific oscillatory-evoked neural responses
      in these structures in the theta and beta bands, which characterize acquisition
      and recombination of cross-modal olfactory-tactile pairs.

PMID- 29212917
TI  - Rhythmic arm cycling training improves walking and neurophysiological integrity
      in chronic stroke: the arms can give legs a helping hand in rehabilitation.
AB  - Training locomotor central pattern-generating networks (CPGs) through arm and leg
      cycling improves walking in chronic stroke. These outcomes are presumed to result
      from enhanced interlimb connectivity and CPG function. The extent to which
      rhythmic arm training activates interlimb CPG networks for locomotion remains
      unclear and was assessed by studying chronic stroke participants before and after
      5 wk of arm cycling training. Strength was assessed bilaterally via maximal
      voluntary isometric contractions in the legs and hands. Muscle activation during
      arm cycling and transfer to treadmill walking were assessed in the more affected
      (MA) and less affected (LA) sides via surface electromyography. Changes to
      interlimb coupling during rhythmic movement were evaluated using modulation of
      cutaneous reflexes elicited by electrical stimulation of the superficial radial
      nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and
      during 1-Hz arm cycling. Clinical function tests assessed walking, balance, and
      motor function. Results show significant changes in function and
      neurophysiological integrity. Training increased bilateral grip strength, force
      during MA plantarflexion, and muscle activation. "Normalization" of cutaneous
      reflex modulation was found during arm cycling. There was enhanced activity in
      the dorsiflexor muscles on the MA side during the swing phase of walking.
      Enhanced interlimb coupling was shown by increased modulation of MA soleus
      stretch reflex amplitudes during arm cycling after training. Clinical evaluations
      showed enhanced walking ability and balance. These results are consistent with
      training-induced changes in CPG function and interlimb connectivity and
      underscore the need for arm training in the functional rehabilitation of walking
      after neurotrauma. NEW & NOTEWORTHY It has been suggested but not tested that
      training the arms may influence rehabilitation of walking due to activation of
      interneuronal patterning networks after stroke. We show that arm cycling training
      improves strength, clinical function, coordination of muscle activity during
      walking, and neurological connectivity between the arms and the legs. The arms
      can, in fact, give the legs a helping hand in rehabilitation of walking after
      stroke.

PMID- 29212920
TI  - Phasic and tonic cell types in the zebra finch auditory caudal mesopallium.
AB  - The caudal mesopallium (CM) is a cortical-level area in the songbird auditory
      pathway where selective, invariant responses to familiar songs emerge. To
      characterize the cell types that perform this computation, we made whole cell
      recordings from brain slices in juvenile zebra finches ( Taeniopygia guttata) of
      both sexes. We found three groups of putatively excitatory neurons with distinct
      firing patterns. Tonic cells produced sustained responses to depolarizing step
      currents, phasic cells produced only a few spikes at the onset, and an
      intermediate group was also phasic but responded for up to a few hundred
      milliseconds. Phasic cells had smaller dendritic fields, higher resting
      potentials, and strong low-threshold outward rectification. Pharmacological
      treatment with voltage-gated potassium channel antagonists 4-aminopyridine and
      alpha-dendrotoxin converted phasic to tonic firing. When stimulated with
      broadband currents, phasic cells fired coherently with frequencies up to 20-30
      Hz, whereas tonic neurons were more responsive to frequencies around 0-10 Hz. The
      distribution of peak coherence frequencies was similar to the distribution of
      temporal modulation rates in zebra finch song. We reproduced these observations
      in a single-compartment biophysical model by varying cell size and the magnitude
      of a slowly inactivating, low-threshold potassium current ( ILT). These data
      suggest that intrinsic dynamics in CM are matched to the temporal statistics of
      conspecific song. NEW & NOTEWORTHY In songbirds, the caudal mesopallium is a key
      brain area involved in recognizing the songs of other individuals. This study
      identifies three cell types in this area with distinct firing patterns (tonic,
      phasic, and intermediate) that reflect differences in cell size and a low
      threshold potassium current. The phasic-firing neurons, which do not have a
      counterpart in mammalian auditory cortex, are better able to follow rapid
      modulations at the frequencies found in song.

PMID- 29212922
TI  - Reward activations and face fields in monkey cingulate motor areas.
AB  - Several premotor areas have been identified within primate cingulate cortex;
      however their function is yet to be uncovered. Recent brain imaging work in
      humans revealed a topographic anatomofunctional overlap between feedback
      processing during exploratory behaviors and the corresponding body fields in the
      rostral cingulate motor area (RCZa), suggesting an embodied representation of
      feedback. In particular, a face field in RCZa processes juice feedback. Here we
      tested an extension of the embodied principle in which unexpected or relevant
      information obtained through the eye or the face would be processed by face
      fields in cingulate motor areas, and whether this applied to monkey cingulate
      cortex. We show that activations for juice reward, eye movement, eye blink, and
      tactile stimulation on the face overlap over two subfields within the cingulate
      sulcus likely corresponding to the rostral and caudal cingulate motor areas. This
      suggests that in monkeys as is the case in humans, behaviorally relevant
      information is processed through multiple cingulate body/effector maps. NEW &
      NOTEWORTHY What is the role of cingulate motor areas? In this study we observed
      in monkeys that, as in humans, neural responses to face-related events, juice
      reward, eye movement, eye blink, and tactile stimulations, clustered redundantly
      in two separate cingulate subfields. This suggests that behaviorally relevant
      information is processed by multiple cingulate effector maps. Importantly, this
      overlap supports the principle that the cingulate cortex processes feedback based
      on where it is experienced on the body.

PMID- 29212921
TI  - BOLD temporal variability differentiates wakefulness from anesthesia-induced
      unconsciousness.
AB  - Even though a number of findings, based on information content or information
      integration, are shown to define neural underpinnings characteristic of a
      conscious experience, the neurophysiological mechanism of consciousness is still
      poorly understood. Here, we investigated the brain activity and functional
      connectivity changes that occur in the isoflurane-anesthetized unconscious state
      in contrast to the awake state in rats (awake and/or anesthetized, n = 68 rats).
      We examined nine information measures previously shown to distinguish between
      conscious states: blood oxygen level-dependent (BOLD) variability, functional
      connectivity strength, modularity, weighted modularity, efficiency, clustering
      coefficient, small-worldness, and spatial and temporal Lempel-Ziv complexity
      measure. We also identified modular membership, seed-based network connectivity,
      and absolute and normalized power spectrums to assess the integrity of the BOLD
      functional networks between awake and anesthesia. fMRI BOLD variability and
      related absolute power were the only information measures significantly higher
      during the awake state compared with isoflurane anesthesia across animals, and
      with varying levels of anesthesia, after correcting for motion and respiration
      confounds. Thus, we conclude that, at least under the specific conditions
      examined here, global measures of information integration/sharing do not properly
      distinguish the anesthetized state from wakefulness, and heightened overall,
      global and local, BOLD variability is the most reliable determinant of conscious
      brain activity relative to isoflurane anesthesia. NEW & NOTEWORTHY Multiple
      metrics previously suggested to be able to distinguish between states of
      consciousness were compared, within and across rats in awake and isoflurane
      anesthesia-induced unconsciousness. All measures tested showed sensitivity to
      confounds, correcting for motion and for respiration changes due to anesthesia.
      Resting state local BOLD variability and the related absolute power were the only
      information measures that robustly differentiated wakefulness states. These
      results caution against the general applicability of global information measures
      in identifying levels of consciousness, thus challenging the popular concept that
      these measures reflect states of consciousness, and also pointing to local signal
      variability as a more reliable indicator of states of wakefulness.

PMID- 29212923
TI  - Response inhibition activates distinct motor cortical inhibitory processes.
AB  - We routinely cancel preplanned movements that are no longer required. If stopping
      is forewarned, proactive processes are engaged to selectively decrease motor
      cortex excitability. However, without advance information there is a nonselective
      reduction in motor cortical excitability. In this study we examined modulation of
      human primary motor cortex inhibitory networks during response inhibition tasks
      with informative and uninformative cues using paired-pulse transcranial magnetic
      stimulation. Long- (LICI) and short-interval intracortical inhibition (SICI),
      indicative of GABAB- and GABAA-receptor mediated inhibition, respectively, were
      examined from motor evoked potentials obtained in task-relevant and task
      irrelevant hand muscles when response inhibition was preceded by informative and
      uninformative cues. When the participants (10 men and 8 women) were cued to stop
      only a subcomponent of the bimanual response, the remaining response was delayed,
      and the extent of delay was greatest in the more reactive context, when cues were
      uninformative. For LICI, inhibition was reduced in both muscles during all types
      of response inhibition trials compared with the pre-task resting baseline. When
      cues were uninformative and left-hand responses were suddenly canceled, task
      relevant LICI positively correlated with response times of the responding right
      hand. In trials where left-hand responding was highly probable or known
      (informative cues), task-relevant SICI was reduced compared with that when cued
      to rest, revealing a motor set indicative of responding. These novel findings
      indicate that the GABAB-receptor-mediated pathway may set a default inhibitory
      tone according to task context, whereas the GABAA-receptor-mediated pathways are
      recruited proactively with response certainty. NEW & NOTEWORTHY We examined how
      informative and uninformative cues that trigger both proactive and reactive
      processes modulate GABAergic inhibitory networks within human primary motor
      cortex. We show that GABAB inhibition was released during the task regardless of
      cue type, whereas GABAA inhibition was reduced when responding was highly
      probable or known compared with rest. GABAB-receptor-mediated inhibition may set
      a default inhibitory tone, whereas GABAA circuits may be modulated proactively
      according to response certainty.

PMID- 29212924
TI  - Robust mixture modeling reveals category-free selectivity in reward region
      neuronal ensembles.
AB  - Classification of neurons into clusters based on their response properties is an
      important tool for gaining insight into neural computations. However, it remains
      unclear to what extent neurons fall naturally into discrete functional
      categories. We developed a Bayesian method that models the tuning properties of
      neural populations as a mixture of multiple types of task-relevant response
      patterns. We applied this method to data from several cortical and striatal
      regions in economic choice tasks. In all cases, neurons fell into only two
      clusters: one multiple-selectivity cluster containing all cells driven by task
      variables of interest and another of no selectivity for those variables. The
      single cluster of task-sensitive cells argues against robust categorical tuning
      in these areas. The no-selectivity cluster was unanticipated and raises important
      questions about what distinguishes these neurons and what role they play.
      Moreover, the ability to formally identify these nonselective cells allows for
      more accurate measurement of ensemble effects by excluding or appropriately down
      weighting them in analysis. Our findings provide a valuable tool for analysis of
      neural data, challenge simple categorization schemes previously proposed for
      these regions, and place useful constraints on neurocomputational models of
      economic choice and control. NEW & NOTEWORTHY We present a Bayesian method for
      formally detecting whether a population of neurons can be naturally classified
      into clusters based on their response tuning properties. We then examine several
      data sets of reward system neurons for variables and find in all cases that
      neurons can be classified into only two categories: a functional class and a non
      task-driven class. These results provide important constraints for neural models
      of the reward system.

PMID- 29212925
TI  - Done in 100 ms: path-dependent visuomotor transformation in the human upper limb.
AB  - A core assumption underlying mental chronometry is that more complex tasks
      increase cortical processing, prolonging reaction times. In this study we show
      that increases in task complexity alter the magnitude, rather than the latency,
      of the output for a circuit that rapidly transforms visual information into motor
      actions. We quantified visual stimulus-locked responses (SLRs), which are changes
      in upper limb muscle recruitment that evolve at a fixed latency ~100 ms after
      novel visual stimulus onset. First, we studied the underlying reference frame of
      the SLR by dissociating the initial eye and hand position. Despite its quick
      latency, we found that the SLR was expressed in a hand-centric reference frame,
      suggesting that the circuit mediating the SLR integrated retinotopic visual
      information with body configuration. Next, we studied the influence of planned
      movement trajectory, requiring participants to prepare and generate either curved
      or straight reaches in the presence of obstacles to attain the same visual
      stimulus location. We found that SLR magnitude was influenced by the planned
      movement trajectory to the same visual stimulus. On the basis of these results,
      we suggest that the circuit mediating the SLR lies in parallel to other well
      studied corticospinal pathways. Although the fixed latency of the SLR precludes
      extensive cortical processing, inputs conveying information relating to task
      complexity, such as body configuration and planned movement trajectory, can
      preset nodes within the circuit underlying the SLR to modulate its magnitude. NEW
      & NOTEWORTHY We studied stimulus-locked responses (SLRs), which are changes in
      human upper limb muscle recruitment that evolve at a fixed latency ~100 ms after
      novel visual stimulus onset. We showed that despite its quick latency, the
      circuitry mediating the SLR transformed a retinotopic visual signal into a hand
      centric motor command that is modulated by the planned movement trajectory. We
      suggest that the circuit generating the SLR is mediated through a
      tectoreticulospinal, rather than a corticospinal, pathway.

PMID- 29212926
TI  - Syrian Hamster as an Animal Model for the Study of Human Influenza Virus
      Infection.
AB  - Ferrets and mice are frequently used as animal models for influenza research.
      However, ferrets are demanding in terms of housing space and handling, whereas
      mice are not naturally susceptible to infection with human influenza A or B
      viruses. Therefore, prior adaptation of human viruses is required for their use
      in mice. In addition, there are no mouse-adapted variants of the recent H3N2
      viruses, because these viruses do not replicate well in mice. In this study, we
      investigated the susceptibility of Syrian hamsters to influenza viruses with a
      view to using the hamster model as an alternative to the mouse model. We found
      that hamsters are sensitive to influenza viruses, including the recent H3N2
      viruses, without adaptation. Although the hamsters did not show weight loss or
      clinical signs of H3N2 virus infection, we observed pathogenic effects in the
      respiratory tracts of the infected animals. All of the H3N2 viruses tested
      replicated in the respiratory organs of the hamsters, and some of them were
      detected in the nasal washes of infected animals. Moreover, a 2009 pandemic
      (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses,
      but not a type B virus, were transmissible by the airborne route in these
      hamsters. Hamsters thus have the potential to be a small-animal model for the
      study of influenza virus infection, including studies of the pathogenicity of
      H3N2 viruses and other strains, as well as for use in H1N1 virus transmission
      studies.IMPORTANCE We found that Syrian hamsters are susceptible to human
      influenza viruses, including the recent H3N2 viruses, without adaptation. We also
      found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2
      viruses, but not a type B virus tested, are transmitted by the airborne route in
      these hamsters. Syrian hamsters thus have the potential to be used as a small
      animal model for the study of human influenza viruses.

PMID- 29212927
TI  - Mutations in the PA Protein of Avian H5N1 Influenza Viruses Affect Polymerase
      Activity and Mouse Virulence.
AB  - To study the influenza virus determinants of pathogenicity, we characterized two
      highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012
      (A/duck/Vietnam/QT1480/2012 [QT1480]) and 2013 (A/duck/Vietnam/QT1728/2013
      [QT1728]) and found that the activity of their polymerase complexes differed
      significantly, even though both viruses were highly pathogenic in mice. Further
      studies revealed that the PA-S343A/E347D (PA with the S-to-A change at position
      343 and the E-to-D change at position 347) mutations reduced viral polymerase
      activity and mouse virulence when tested in the genetic background of QT1728
      virus. In contrast, the PA-343S/347E mutations increased the polymerase activity
      of QT1480 and the virulence of a low-pathogenic H5N1 influenza virus. The PA-343S
      residue (which alone increased viral polymerase activity and mouse virulence
      significantly relative to viral replication complexes encoding PA-343A) is
      frequently found in H5N1 influenza viruses of several subclades; infection with a
      virus possessing this amino acid may pose an increased risk to humans.IMPORTANCE
      H5N1 influenza viruses cause severe infections in humans with a case fatality
      rate that exceeds 50%. The factors that determine the high virulence of these
      viruses in humans are not fully understood. Here, we identified two amino acid
      changes in the viral polymerase PA protein that affect the activity of the viral
      polymerase complex and virulence in mice. Infection with viruses possessing these
      amino acid changes may pose an increased risk to humans.

PMID- 29212928
TI  - Autographa californica Multiple Nucleopolyhedrovirus ac75 Is Required for the
      Nuclear Egress of Nucleocapsids and Intranuclear Microvesicle Formation.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf75 (ac75) is a
      highly conserved gene of unknown function. In this study, we constructed an ac75
      knockout AcMNPV bacmid and investigated the role of ac75 in the baculovirus life
      cycle. The expression and distribution of the Ac75 protein were characterized,
      and its interaction with another viral protein was analyzed to further understand
      its function. Our data indicated that ac75 was required for the nuclear egress of
      nucleocapsids, intranuclear microvesicle formation, and subsequent budded virion
      (BV) formation, as well as occlusion-derived virion (ODV) envelopment and
      embedding of ODVs into polyhedra. Western blot analyses showed that two forms, of
      18 and 15 kDa, of FLAG-tagged Ac75 protein were detected. Ac75 was associated
      with both nucleocapsid and envelope fractions of BVs but with only the
      nucleocapsid fraction of ODVs; the 18-kDa form was associated with only BVs,
      whereas the 15-kDa form was associated with both types of virion. Ac75 was
      localized predominantly in the intranuclear ring zone during infection and
      exhibited a nuclear rim distribution during the early phase of infection. A phase
      separation assay suggested that Ac75 was not an integral membrane protein. A
      coimmunoprecipitation assay revealed an interaction between Ac75 and the integral
      membrane protein Ac76, and bimolecular fluorescence complementation assays
      identified the sites of the interaction within the cytoplasm and at the nuclear
      membrane and ring zone in AcMNPV-infected cells. Our results have identified ac75
      as a second gene that is required for both the nuclear egress of nucleocapsids
      and the formation of intranuclear microvesicles.IMPORTANCE During the baculovirus
      life cycle, the morphogenesis of both budded virions (BVs) and occlusion-derived
      virions (ODVs) is proposed to involve a budding process at the nuclear membrane,
      which occurs while nucleocapsids egress from the nucleus or when intranuclear
      microvesicles are produced. However, the exact mechanism of virion morphogenesis
      remains unknown. In this study, we identified ac75 as a second gene, in addition
      to ac93, that is essential for the nuclear egress of nucleocapsids, intranuclear
      microvesicle formation, and subsequent BV formation, as well as ODV envelopment
      and embedding of ODVs into polyhedra. Ac75 is not an integral membrane protein.
      However, it interacts with an integral membrane protein (Ac76) and is associated
      with the nuclear membrane. These data enhance our understanding of the
      commonalities between nuclear egress of nucleocapsids and intranuclear
      microvesicle formation and may help to reveal insights into the mechanism of
      baculovirus virion morphogenesis.

PMID- 29212929
TI  - Nucleic Acid Polymers Are Active against Hepatitis Delta Virus Infection In
      Vitro.
AB  - In this study, an in vitro infection model for the hepatitis delta virus (HDV)
      was used to evaluate the antiviral effects of phosphorothioate nucleic acid
      polymers (NAPs) and investigate their mechanism of action. The results show that
      NAPs inhibit HDV infection at concentrations less than 4 MUM in cultures of
      differentiated human hepatoma cells. NAPs were shown to be active at viral entry
      but inactive postentry on HDV RNA replication. Inhibition was independent of the
      NAP nucleotide sequence but dependent on both size and amphipathicity of the
      polymer. NAP antiviral activity was effective against HDV virions bearing the
      main hepatitis B virus (HBV) immune escape substitutions (D144A and G145R) and
      was pangenomic with regard to HBV envelope proteins. Furthermore, similar to
      immobilized heparin, immobilized NAPs could bind HDV particles, suggesting that
      entry inhibition was due, at least in part, to preventing attachment of the virus
      to cell surface glycosaminoglycans. The results document NAPs as a novel class of
      antiviral compounds that can prevent HDV propagation.IMPORTANCE HDV infection
      causes the most severe form of viral hepatitis in humans and one of the most
      difficult to cure. Currently, treatments are limited to long-term administration
      of interferon at high doses, which provide only partial efficacy. There is thus
      an urgent need for innovative approaches to identify new antiviral against HDV.
      The significance of our study is in demonstrating that nucleic acid polymers
      (NAPs) are active against HDV by targeting the envelope of HDV virions. In an in
      vitro infection assay, NAP activity was recorded at concentrations less than 4
      MUM in the absence of cell toxicity. Furthermore, the fact that NAPs could block
      HDV at viral entry suggests their potential to control the spread of HDV in a
      chronically HBV-infected liver. In addition, NAP anti-HDV activity was pangenomic
      with regard to HBV envelope proteins and not circumvented by HBsAg substitutions
      associated with HBV immune escape.

PMID- 29212930
TI  - Control of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Infection by Eliminating
      Envelope Protein-Positive Cells with Recombinant Vesicular Stomatitis Viruses
      Encoding HTLV-1 Primary Receptor.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell
      leukemia (ATL), which is frequently resistant to currently available therapies
      and has a very poor prognosis. To prevent the development of ATL among carriers,
      it is important to control HTLV-1-infected cells in infected individuals.
      Therefore, the establishment of novel therapies with drugs specifically targeting
      infected cells is urgently required. This study aimed to develop a potential
      therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack
      an envelope glycoprotein G and instead encode an HTLV-1 receptor with human
      glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate
      proteoglycans (HSPGs), including syndecan 1 (SDC1), designated VSVDeltaG-GL,
      VSVDeltaG-NP, or VSVDeltaG-SD, respectively. In an attempt to enhance the
      infectivity of rVSV against HTLV-1-infected cells, we also constructed rVSVs with
      a combination of two or three receptor genes, designated VSVDeltaG-GLN and
      VSVDeltaG-GLNS, respectively. The present study demonstrates VSVDeltaG-GL,
      VSVDeltaG-NP, VSVDeltaG-GLN, and VSVDeltaG-GLNS have tropism for HTLV-1 envelope
      (Env)-expressing cells. Notably, the inoculation of VSVDeltaG-GL or VSVDeltaG-NP
      significantly eliminated HTLV-1-infected cells under the culture conditions.
      Furthermore, in an HTLV-1-infected humanized mouse model, VSVDeltaG-NP was
      capable of efficiently preventing HTLV-1-induced leukocytosis in the periphery
      and eliminating HTLV-1-infected Env-expressing cells in the lymphoid tissues. In
      summary, an rVSV engineered to express HTLV-1 primary receptor, especially human
      NRP1, may represent a drug candidate that has potential for the development of
      unique virotherapy against HTLV-1 de novo infection.IMPORTANCE Although several
      anti-ATL therapies are currently available, ATL is still frequently resistant to
      therapeutic approaches, and its prognosis remains poor. Control of HTLV-1 de novo
      infection or expansion of HTLV-1-infected cells in the carrier holds considerable
      promise for the prevention of ATL development. In this study, we developed rVSVs
      that specifically target and kill HTLV-1 Env-expressing cells (not ATL cells,
      which generally do not express Env in vivo) through replacement of the G gene
      with HTLV-1 receptor gene(s) in the VSV genome. Notably, an rVSV engineered to
      express human NRP1 controlled the number of HTLV-1-infected Env-expressing cells
      in vitro and in vivo, suggesting the present approach may be a promising
      candidate for novel anti-HTLV-1 virotherapy in HTLV-1 carriers, including as a
      prophylactic treatment against the development of ATL.

PMID- 29212931
TI  - Suppression of Zika Virus Infection and Replication in Endothelial Cells and
      Astrocytes by PKA Inhibitor PKI 14-22.
AB  - The recent outbreak of Zika virus (ZIKV), a reemerging flavivirus, and its
      associated neurological disorders, such as Guillain-Barre (GB) syndrome and
      microcephaly, have generated an urgent need to develop effective ZIKV vaccines
      and therapeutic agents. Here, we used human endothelial cells and astrocytes,
      both of which represent key cell types for ZIKV infection, to identify potential
      inhibitors of ZIKV replication. Because several pathways, including the AMP
      activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated
      protein kinase (MAPK) signaling pathways, have been reported to play important
      roles in flavivirus replication, we tested inhibitors and agonists of these
      pathways for their effects on ZIKV replication. We identified the PKA inhibitor
      PKI 14-22 (PKI) to be a potent inhibitor of ZIKV replication. PKI effectively
      suppressed the replication of ZIKV from both the African and Asian/American
      lineages with a high efficiency and minimal cytotoxicity. While ZIKV infection
      does not induce PKA activation, endogenous PKA activity is essential for
      supporting ZIKV replication. Interestingly, in addition to PKA, PKI also
      inhibited another unknown target(s) to block ZIKV replication. PKI inhibited ZIKV
      replication at the postentry stage by preferentially affecting negative-sense RNA
      synthesis as well as viral protein translation. Together, these results have
      identified a potential inhibitor of ZIKV replication which could be further
      explored for future therapeutic application.IMPORTANCE There is an urgent need to
      develop effective vaccines and therapeutic agents against Zika virus (ZIKV)
      infection, a reemerging flavivirus associated with neurological disorders,
      including Guillain-Barre (GB) syndrome and microcephaly. By screening for
      inhibitors of several cellular pathways, we have identified the PKA inhibitor PKI
      14-22 (PKI) to be a potent inhibitor of ZIKV replication. We show that PKI
      effectively suppresses the replication of all ZIKV strains tested with minimal
      cytotoxicity to human endothelial cells and astrocytes, two key cell types for
      ZIKV infection. Furthermore, we show that PKI inhibits ZIKV negative-sense RNA
      synthesis and viral protein translation. This study has identified a potent
      inhibitor of ZIKV infection which could be further explored for future
      therapeutic application.

PMID- 29212932
TI  - Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and
      Mucosal Human Papillomaviruses.
AB  - The amino terminus of the human papillomavirus (HPV) minor capsid protein L2
      contains a major cross-neutralization epitope which provides the basis for the
      development of a broadly protecting HPV vaccine. A wide range of protection
      against different HPV types would eliminate one of the major drawbacks of the
      commercial, L1-based prophylactic vaccines. Previously, we have reported that
      insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin
      protein generates a potent antigen inducing comprehensive protection against
      different animal and human papillomaviruses. We also reported, however, that
      although protection is broad, some oncogenic HPV types escape the neutralizing
      antibody response, if L2 epitopes from single HPV types are used as immunogen. We
      were able to compensate for this by applying a mix of thioredoxin proteins
      carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost
      efficient HPV prophylactic vaccines is one of our objectives, this approach is
      not feasible as it requires the development of multiple good manufacturing
      production processes in combination with a complex vaccine formulation. Here, we
      report the development of a thermostable thioredoxin-based single-peptide vaccine
      carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens
      have excellent abilities in respect to broadness of protection and robustness of
      induced immune responses. To further increase immunogenicity, we fused the
      thioredoxin L2 polytope antigen with a heptamerization domain. In the final
      vaccine design, we achieve protective responses against all 14 oncogenic HPV
      types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of
      cutaneous HPVs.IMPORTANCE Infections by a large number of human papillomaviruses
      lead to malignant and nonmalignant disease. Current commercial vaccines based on
      virus-like particles (VLPs) effectively protect against some HPV types but fail
      to do so for most others. Further, only about a third of all countries have
      access to the VLP vaccines. The minor capsid protein L2 has been shown to contain
      so-called neutralization epitopes within its N terminus. We designed polytopes
      comprising the L2 epitope amino acids 20 to 38 of up to 11 different mucosal HPV
      types and inserted them into the scaffold of thioredoxin derived from a
      thermophile archaebacterium. The antigen induced neutralizing antibody responses
      in mice and guinea pigs against 26 mucosal and cutaneous HPV types. Further,
      addition of a heptamerization domain significantly increased the immunogenicity.
      The final vaccine design comprising a heptamerized L2 8-mer thioredoxin single
      peptide antigen with excellent thermal stability might overcome some of the
      limitations of the current VLP vaccines.

PMID- 29212934
TI  - Influenza A virus reassortment is limited by anatomical compartmentalization
      following co-infection via distinct routes.
AB  - Exchange of gene segments through reassortment is a major feature of influenza A
      virus evolution and frequently contributes to the emergence of novel epidemic,
      pandemic and zoonotic strains. It has long been evident that viral
      diversification through reassortment is constrained by genetic incompatibility
      between divergent parental viruses. In contrast, the role of virus-extrinsic
      factors in determining the likelihood of reassortment has remained unclear. To
      evaluate the impact of such factors in the absence of confounding effects of
      segment mismatch, we previously reported an approach in which reassortment
      between wild-type (wt) and genetically tagged variant (var) viruses of the same
      strain is measured. Here, using wt/var systems in the A/Netherlands/602/2009
      (pH1N1) and A/Panama/2007/99 (H3N2) strain backgrounds, we have tested whether
      inoculation of parental viruses into distinct sites within the respiratory tract
      limits their reassortment. Using a ferret model, matched parental viruses were
      either co-inoculated intranasally, or one virus was instilled intranasally while
      the second was instilled intratracheally. Dual intranasal inoculation resulted in
      robust reassortment for wt/var viruses of both strain backgrounds. In contrast,
      when infections were initiated simultaneously at distinct sites, strong
      compartmentalization of viral replication was observed and minimal reassortment
      was detected. The observed lack of viral spread between upper and lower
      respiratory tissues may be attributable to localized exclusion of super-infection
      within the host, mediated by innate immune responses. Our findings indicate that
      dual infections in nature are more likely to result in reassortment if viruses
      are seeded into similar anatomical locations and have matched tissue
      tropisms.ImportanceGenetic exchange between influenza A viruses (IAVs) through
      reassortment can facilitate the emergence of antigenically drifted seasonal
      strains and plays a prominent role in the development of pandemics. Typical human
      influenza is concentrated in the upper respiratory tract; however, lower
      respiratory tract (LRT) infection is an important feature of severe cases, which
      are more common in the very young, the elderly, and individuals with underlying
      conditions. In addition to host factors, viral characteristics and mode of
      transmission can also increase the likelihood of LRT infection: certain zoonotic
      IAVs are thought to favor the LRT and transmission via small droplets allows
      direct seeding into lower respiratory tissues. Toward gauging the likelihood of
      reassortment in co-infected hosts, we assessed the extent to which initiation of
      infection at distinct respiratory sites impacts reassortment frequency. Our
      results reveal that spatially distinct inoculation results in anatomical
      compartmentalization of infection, which in turn strongly limits reassortment.

PMID- 29212933
TI  - Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein.
AB  - We have produced a new Ebola virus pseudotype, E-S-FLU, that can be handled in
      biosafety level 1/2 containment for laboratory analysis. The E-S-FLU virus is a
      single-cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes
      enhanced green fluorescence protein as a reporter that replaces the influenza
      virus hemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus
      glycoprotein as a stable transmembrane protein for E-S-FLU virus production.
      Infection of cells with the E-S-FLU virus was dependent on the Niemann-Pick C1
      protein, which is the well-characterized receptor for Ebola virus entry at the
      late endosome/lysosome membrane. The E-S-FLU virus was neutralized specifically
      by an anti-Ebolavirus glycoprotein antibody and a variety of small drug molecules
      that are known to inhibit the entry of wild-type Ebola virus. To demonstrate the
      application of this new Ebola virus pseudotype, we show that a single laboratory
      batch was sufficient to screen a library (LOPAC1280; Sigma) of 1,280
      pharmacologically active compounds for inhibition of virus entry. A total of 215
      compounds inhibited E-S-FLU virus infection, while only 22 inhibited the control
      H5-S-FLU virus coated in H5 hemagglutinin. These inhibitory compounds have very
      dispersed targets and mechanisms of action, e.g., calcium channel blockers,
      estrogen receptor antagonists, antihistamines, serotonin uptake inhibitors, etc.,
      and this correlates with inhibitor screening results obtained with other
      pseudotypes or wild-type Ebola virus in the literature. The E-S-FLU virus is a
      new tool for Ebola virus cell entry studies and is easily applied to high
      throughput screening assays for small-molecule inhibitors or
      antibodies.IMPORTANCE Ebola virus is in the Filoviridae family and is a biosafety
      level 4 pathogen. There are no FDA-approved therapeutics for Ebola virus. These
      characteristics warrant the development of surrogates for Ebola virus that can be
      handled in more convenient laboratory containment to study the biology of the
      virus and screen for inhibitors. Here we characterized a new surrogate, named E-S
      FLU virus, that is based on a disabled influenza virus core coated with the Ebola
      virus surface protein but does not contain any genetic information from the Ebola
      virus itself. We show that E-S-FLU virus uses the same cell entry pathway as wild
      type Ebola virus. As an example of the ease of use of E-S-FLU virus in biosafety
      level 1/2 containment, we showed that a single production batch could provide
      enough surrogate virus to screen a standard small-molecule library of 1,280
      candidates for inhibitors of viral entry.

PMID- 29212935
TI  - Tetraspanin CD63 Bridges Autophagic and Endosomal Processes To Regulate Exosomal
      Secretion and Intracellular Signaling of Epstein-Barr Virus LMP1
AB  - The tetraspanin protein CD63 has been recently described as a key factor in
      extracellular vesicle (EV) production and endosomal cargo sorting. In the context
      of Epstein-Barr virus (EBV) infection, CD63 is required for the efficient
      packaging of the major viral oncoprotein latent membrane protein 1 (LMP1) into
      exosomes and other EV populations and acts as a negative regulator of LMP1
      intracellular signaling. Accumulating evidence has also pointed to intersections
      of the endosomal and autophagy pathways in maintaining cellular secretory
      processes and as sites for viral assembly and replication. Indeed, LMP1 can
      activate the mammalian target of rapamycin (mTOR) pathway to suppress host cell
      autophagy and facilitate cell growth and proliferation. Despite the growing
      recognition of cross talk between endosomes and autophagosomes and its relevance
      to viral infection, little is understood about the molecular mechanisms governing
      endosomal and autophagy convergence. Here, we demonstrate that CD63-dependent
      vesicle protein secretion directly opposes intracellular signaling activation
      downstream of LMP1, including mTOR-associated proteins. Conversely, disruption of
      normal autolysosomal processes increases LMP1 secretion and dampens signal
      transduction by the viral protein. Increases in mTOR activation following CD63
      knockout are coincident with the development of serum-dependent autophagic
      vacuoles that are acidified in the presence of high LMP1 levels. Altogether,
      these findings suggest a key role of CD63 in regulating the interactions between
      endosomal and autophagy processes and limiting cellular signaling activity in
      both noninfected and virally infected cells.IMPORTANCE The close connection
      between extracellular vesicles and viruses is becoming rapidly and more widely
      appreciated. EBV, a human gamma herpesvirus that contributes to the progression
      of a multitude of lymphomas and carcinomas in immunocompromised or genetically
      susceptible populations, packages its major oncoprotein, LMP1, into vesicles for
      secretion. We have recently described a role of the host cell protein CD63 in
      regulating intracellular signaling of the viral oncoprotein by shuttling LMP1
      into exosomes. Here, we provide strong evidence of the utility of CD63-dependent
      EVs in regulating global intracellular signaling, including mTOR activation by
      LMP1. We also demonstrate a key role of CD63 in coordinating endosomal and
      autophagic processes to regulate LMP1 levels within the cell. Overall, this study
      offers new insights into the complex intersection of cellular secretory and
      degradative mechanisms and the implications of these processes in viral
      replication.

PMID- 29212936
TI  - Structural Insight into a Human Neutralizing Antibody against Influenza Virus
      H7N9.
AB  - Since its first emergence in East China in early 2013, many cases of avian
      influenza A H7N9 have been reported. The disease has extended to 22 provinces in
      mainland China and some surrounding areas. Strategies to combat viral infection
      are urgently needed. We previously isolated a human monoclonal antibody, HNIgGA6,
      that neutralized the H7N9 virus both in vitro and in vivo In this study, we
      determined the crystal structure of viral hemagglutinin (HA) globular head bound
      to the fragment antigen-binding region (Fab) of HNIgGA6. The crystal structure
      shows that the tip of the HNIgGA6 heavy-chain complementarity-determining region
      3 (HCDR3) directly interposes into the receptor binding site (RBS) and mimics, in
      many respects, the interaction of the sialic acid receptor. Three residues at
      Y98, H183, and E190, which are critical to human cellular receptor binding, are
      also essential for HNIgGA6 recognition. Meanwhile, dual mutations at V186G and
      L226Q in RBS were able to disrupt viral HA1 binding with the antibody. Our study
      provides a better understanding of the mechanism for protective antibody
      recognition and a sound foundation for the design of therapeutic drugs and
      vaccines against H7N9 influenza.IMPORTANCE Neutralization by antibody is one of
      the most important mechanisms for a host to defend against viral infections.
      Human-originated antibody HNIgGA6 was generated in response to the natural
      infectious H7N9 virus and showed potential for use in suppression of H7N9
      infection, with possible therapeutic implications. The crystal structure of the
      HNIgGA6/HA1 complex provided new insight into the protective immune response to
      H7N9 virus in humans, as well as possibilities for the development of effective
      H7N9 pandemic vaccines and antiviral molecules.

PMID- 29212937
TI  - Experimental Adaptive Evolution of Simian Immunodeficiency Virus SIVcpz to
      Pandemic Human Immunodeficiency Virus Type 1 by Using a Humanized Mouse Model.
AB  - Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS,
      originated from simian immunodeficiency virus from chimpanzees (SIVcpz), the
      precursor of the human virus, approximately 100 years ago. This indicates that
      HIV-1 has emerged through the cross-species transmission of SIVcpz from
      chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into
      pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz
      strains (MB897, EK505, and MT145), four pandemic HIV-1 strains (NL4-3, NLCSFV3,
      JRCSF, and AD8), and two nonpandemic HIV-1 strains (YBF30 and DJO0131). Humanized
      mice infected with SIVcpz strain MB897, a virus phylogenetically similar to
      pandemic HIV-1, exhibited a peak viral load comparable to that of mice infected
      with pandemic HIV-1, while peak viral loads of mice infected with SIVcpz strain
      EK505 or MT145 as well as nonpandemic HIV-1 strains were significantly lower.
      These results suggest that SIVcpz strain MB897 is preadapted to humans, unlike
      the other SIVcpz strains. Moreover, viral RNA sequencing of MB897-infected
      humanized mice identified a nonsynonymous mutation in env, a G413R substitution
      in gp120. The infectivity of the gp120 G413R mutant of MB897 was significantly
      higher than that of parental MB897. Furthermore, we demonstrated that the gp120
      G413R mutant of MB897 augments the capacity for viral replication in both in
      vitro cell cultures and humanized mice. Taken together, this is the first
      experimental investigation to use an animal model to demonstrate a gain-of
      function evolution of SIVcpz into pandemic HIV-1.IMPORTANCE From the mid-20th
      century, humans have been exposed to the menace of infectious viral diseases,
      such as severe acute respiratory syndrome coronavirus, Ebola virus, and Zika
      virus. These outbreaks of emerging/reemerging viruses can be triggered by cross
      species viral transmission from wild animals to humans, or zoonoses. HIV-1, the
      causative agent of AIDS, emerged by the cross-species transmission of SIVcpz, the
      HIV-1 precursor in chimpanzees, around 100 years ago. However, the process by
      which SIVcpz evolved to become HIV-1 in humans remains unclear. Here, by using a
      hematopoietic stem cell-transplanted humanized-mouse model, we experimentally
      recapitulate the evolutionary process of SIVcpz to become HIV-1. We provide
      evidence suggesting that a strain of SIVcpz, MB897, preadapted to infect humans
      over other SIVcpz strains. We further demonstrate a gain-of-function evolution of
      SIVcpz in infected humanized mice. Our study reveals that pandemic HIV-1 has
      emerged through at least two steps: preadaptation and subsequent gain-of-function
      mutations.

PMID- 29212938
TI  - Subcellular Localization and Functional Characterization of GII.4 Norovirus
      Encoded NTPase.
AB  - The genotype II.4 (GII.4) variants of human noroviruses (HuNVs) are recognized as
      the major agent of global gastroenteritis outbreaks. Due to the lack of an
      efficient cell culture system for HuNV propagation, the exact roles of HuNV
      encoded nonstructural proteins (including Nterm, NTPase, P22, VPg, Pro, and RdRp)
      in viral replication or pathogenesis have not yet been fully understood. Here, we
      report the molecular characterization of the GII.4 HuNV-encoded NTPase
      (designated GII-NTPase). Results from our studies showed that GII-NTPase forms
      vesicular or nonvesicular textures in the cell cytoplasm, and the nonvesicular
      fraction of GII-NTPase significantly localizes to the endoplasmic reticulum (ER)
      or mitochondria. Deletion analysis revealed that the N-terminal 179-amino-acid
      (aa) region of GII-NTPase is required for vesicle formation and for ER
      colocalization, whereas the C-terminal region is involved in mitochondrial
      colocalization. In particular, two mitochondrion-targeting domains were
      identified in the C-terminal region of GII-NTPase which perfectly colocalized
      with mitochondria when the N-terminal region of GII-NTPase was deleted. However,
      the corresponding C-terminal portions of NTPase derived from the GI HuNV did not
      show mitochondrial colocalization. We also found that GII-NTPase physically
      interacts with itself as well as with Nterm and P22, but not VPg, Pro, and RdRp,
      in cells. The Nterm- and P22-interacting region was mapped to the N-terminal 179
      aa region of GII-NTPase, whereas the self-assembly of GII-NTPase could be
      achieved via a head-to-head, tail-to-tail, or head-to-tail configuration. More
      importantly, we demonstrate that GII-NTPase possesses a proapoptotic activity,
      which can be further enhanced by coexpression with Nterm or P22.IMPORTANCE
      Despite the importance of human norovirus GII.4 variants in global
      gastroenteritis outbreaks, the basic biological functions of the viral
      nonstructural proteins in cells remain rarely investigated. In this report, we
      focus our studies on characteristics of the GII.4 norovirus-encoded NTPase (GII
      NTPase). We unexpectedly find that GII-NTPase can perfectly colocalize with
      mitochondria after its N-terminal region is deleted. However, such a phenomenon
      is not observed for NTPase encoded by a GI strain. We further reveal that the N
      terminal 179-aa region of GII-NTPase is sufficient to mediate (i) vesicle
      formation, (ii) ER colocalization, (iii) the interaction with two other
      nonstructural proteins, including Nterm and P22, (iv) the formation of homodimers
      or homo-oligomers, and (v) the induction of cell apoptosis. Taken together, our
      findings emphasize that the virus-encoded NTPase must have multiple activities
      during viral replication or pathogenesis; however, these activities may vary
      somewhat among different genogroups.

PMID- 29212939
TI  - The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein
      Plays a Key Role in Membrane Fusion.
AB  - Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F)
      protein, which undergoes a conformational change to facilitate the merger of
      viral and host lipid membrane envelopes. The RSV F protein comprises a trimer of
      disulfide-bonded F1 and F2 subunits that is present on the virion surface in a
      metastable prefusion state. This prefusion form is readily triggered to undergo
      refolding to bring two heptad repeats (heptad repeat A [HRA] and HRB) into close
      proximity to form a six-helix bundle that stabilizes the postfusion form and
      provides the free energy required for membrane fusion. This process can be
      triggered independently of other proteins. Here, we have performed a
      comprehensive analysis of a third heptad repeat region, HRC (amino acids 75 to
      97), an amphipathic alpha-helix that lies at the interface of the prefusion F
      trimer and is a major structural feature of the F2 subunit. We performed alanine
      scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in
      transient cell culture for expression, proteolytic processing, cell surface
      localization, protein conformation, and membrane fusion. Functional
      characterization revealed a striking distribution of activity in which fusion
      increasing mutations localized to one side of the helical face, while fusion
      decreasing mutations clustered on the opposing face. Here, we propose a model in
      which HRC plays a stabilizing role within the globular head for the prefusion F
      trimer and is potentially involved in the early events of triggering, prompting
      fusion peptide release and transition into the postfusion state.IMPORTANCE RSV is
      recognized as the most important viral pathogen among pediatric populations
      worldwide, yet no vaccine or widely available therapeutic treatment is available.
      The F protein is critical for the viral replication process and is the major
      target for neutralizing antibodies. Recent years have seen the development of
      prefusion stabilized F protein-based approaches to vaccine design. A detailed
      understanding of the specific domains and residues that contribute to protein
      stability and fusion function is fundamental to such efforts. Here, we present a
      comprehensive mutagenesis-based study of a region of the RSV F2 subunit (amino
      acids 75 to 97), referred to as HRC, and propose a role for this helical region
      in maintaining the delicate stability of the prefusion form.

PMID- 29212940
TI  - HIV-1 Envelope Glycoprotein Trafficking through the Endosomal Recycling
      Compartment Is Required for Particle Incorporation.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)
      encodes specific trafficking signals within its long cytoplasmic tail (CT) that
      regulate incorporation into HIV-1 particles. Rab11-family interacting protein 1C
      (FIP1C) and Rab14 are host trafficking factors required for Env particle
      incorporation, suggesting that Env undergoes sorting from the endosomal recycling
      compartment (ERC) to the site of particle assembly on the plasma membrane. We
      disrupted outward sorting from the ERC by expressing a C-terminal fragment of
      FIP1C (FIP1C560-649) and examined the consequences on Env trafficking and
      incorporation into particles. FIP1C560-649 reduced cell surface levels of Env and
      prevented its incorporation into HIV-1 particles. Remarkably, Env was trapped in
      an exaggerated perinuclear ERC in a CT-dependent manner. Mutation of either the
      Yxxphi endocytic motif or the YW795 motif in the CT prevented Env trapping in the
      ERC and restored incorporation into particles. In contrast, simian
      immunodeficiency virus SIVmac239 Env was not retained in the ERC, while
      substitution of the HIV-1 CT for the SIV CT resulted in SIV Env retention in this
      compartment. These results provide the first direct evidence that Env traffics
      through the ERC and support a model whereby HIV-1 Env is specifically targeted to
      the ERC prior to FIP1C- and CT-dependent outward sorting to the particle assembly
      site on the plasma membrane.IMPORTANCE The HIV envelope protein is an essential
      component of the viral particle. While many aspects of envelope protein structure
      and function have been established, the pathway it follows in the cell prior to
      reaching the site of particle assembly is not well understood. The envelope
      protein has a very long cytoplasmic tail that interacts with the host cell
      trafficking machinery. Here, we utilized a truncated form of the trafficking
      adaptor FIP1C protein to arrest the intracellular transport of the envelope
      protein, demonstrating that it becomes trapped inside the cell within the
      endosomal recycling compartment. Intracellular trapping resulted in a loss of
      envelope protein on released particles and a corresponding loss of infectivity.
      Mutations of specific trafficking motifs in the envelope protein tail prevented
      its trapping in the recycling compartment. These results establish that
      trafficking to the endosomal recycling compartment is an essential step in HIV
      envelope protein particle incorporation.

PMID- 29212941
TI  - A novel Sulfolobus virus with an exceptional capsid architecture.
AB  - A novel archaeal virus, denoted Sulfolobus ellipsoid virus 1 (SEV1), was isolated
      from an acidic hot spring in Costa Rica. The morphologically unique virion of
      SEV1 contains a protein capsid with 16 regularly spaced striations and an 11-nm
      thick envelope. The capsid exhibits an unusual architecture in which the viral
      DNA, probably in the form of a nucleoprotein filament, wraps around the
      longitudinal axis of the virion in a plane to form a multilayered disk-like
      structure with a central hole, and 16 of these structures are stacked to generate
      a spool-like capsid. SEV1 harbors a linear double-stranded DNA genome of ~23 kb,
      which encodes 38 predicted open reading frames (ORFs). Among the few ORFs with a
      putative function is a gene encoding a protein-primed DNA polymerase. Six-fold
      symmetrical virus-associated pyramids (VAPs) appear on the surface of the SEV1
      infected cells, which are ruptured to allow the formation of a hexagonal opening
      and subsequent release of the progeny virus particles. Notably, the SEV1 virions
      acquire the lipid membrane in the cytoplasm of the host cell. The lipid
      composition of the viral envelope correlates with that of the cell membrane.
      These results suggest the use of a unique mechanism by SEV1 in membrane
      biogenesis.IMPORTANCE Investigation of archaeal viruses has greatly expanded our
      knowledge of the virosphere and its role in the evolution of life. Here we show
      that Sulfolobus ellipsoid virus 1 (SEV1), an archaeal virus isolated from a hot
      spring in Costa Rica, exhibits a novel viral shape and an unusual capsid
      architecture. The SEV1 DNA wraps multiple times in a plane around the
      longitudinal axis of the virion to form a disk-like structure, and 16 of these
      structures are stacked to generate a spool-like capsid. The virus acquires its
      envelope intracellularly and exits the host cell by creating a hexagonal hole on
      the host cell surface. These results shed significant light on the diversity of
      viral morphogenesis.

PMID- 29212942
TI  - Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection.
AB  - HIV-1 elite controllers (EC) maintain undetectable viral load (VL) in the absence
      of antiretroviral treatment. However, these subjects have heterogeneous clinical
      outcomes including a proportion loosing HIV-1 control over time. In this work we
      compared, in a longitudinal design, transient EC, analyzed before and after the
      loss of virological control, versus persistent EC. The aim was to identify
      factors leading to the loss of natural virological control of HIV-1-infection
      with a longitudinal retrospective study design. Gag-specific T-cell response was
      assessed by in vitro intracellular poly-cytokine production quantified by flow
      cytometry. Viral diversity and sequence-dating were performed in proviral DNA by
      PCR amplification at limiting dilution in env and gag genes. The expression
      profile of 70 serum cytokines and chemokines was assessed by multiplex
      immunoassays. We identified transient EC as subjects with low Gag-specific T-cell
      polyfunctionality, high viral diversity and high proinflammatory cytokines levels
      before the loss of control. Gag-specific T-cell polyfunctionality was inversely
      associated with viral diversity in transient controllers before the loss of
      control (r=-0.8; p=0.02). RANTES was a potential biomarker of transient control.
      This study identified, virological and immunological factors including
      inflammatory biomarkers associated with two different phenotypes within EC. These
      results may allow a more accurate definition of EC, which could help in a better
      clinical management of these individuals and in the development of future
      curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who
      have the extraordinary capacity to maintain undetectable viral load levels in the
      absence of antiretroviral treatment, the so called HIV-1 elite controllers (EC).
      However, there is a proportion within these subjects that eventually loses this
      capability. In this work we found differences in virological and immune factors
      including soluble inflammatory biomarkers between subjects with persistent
      control of viral replication and EC that will loss the virological control. The
      identification of these factors could be a key point for a right medical care of
      those EC who are going to lose the natural control of viral replication, and for
      the design of future immunotherapeutic strategies using as a model the natural
      persistent control of HIV-infection.

PMID- 29212945
TI  - Refining the Roles of Neuroligins in Synapse Development and Function: A
      Reductionist Conditional Knock-out Approach.

PMID- 29212943
TI  - The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth
      Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers.
AB  - Productive picornavirus infection requires the hijacking of host cell pathways to
      aid with the different stages of virus entry, synthesis of the viral polyprotein,
      and viral genome replication. Many picornaviruses, including foot-and-mouth
      disease virus (FMDV), assemble capsids via the multimerization of several copies
      of a single capsid precursor protein into a pentameric subunit which further
      encapsidates the RNA. Pentamer formation is preceded by co- and posttranslational
      modification of the capsid precursor (P1-2A) by viral and cellular enzymes and
      the subsequent rearrangement of P1-2A into a structure amenable to pentamer
      formation. We have developed a cell-free system to study FMDV pentamer assembly
      using recombinantly expressed FMDV capsid precursor and 3C protease. Using this
      assay, we have shown that two structurally different inhibitors of the cellular
      chaperone heat shock protein 90 (hsp90) impeded FMDV capsid precursor processing
      and subsequent pentamer formation. Treatment of FMDV permissive cells with the
      hsp90 inhibitor prior to infection reduced the endpoint titer by more than 10
      fold while not affecting the activity of a subgenomic replicon, indicating that
      translation and replication of viral RNA were unaffected by the drug.IMPORTANCE
      FMDV of the Picornaviridae family is a pathogen of huge economic importance to
      the livestock industry due to its effect on the restriction of livestock movement
      and necessary control measures required following an outbreak. The study of FMDV
      capsid assembly, and picornavirus capsid assembly more generally, has tended to
      be focused upon the formation of capsids from pentameric intermediates or the
      immediate cotranslational modification of the capsid precursor protein. Here, we
      describe a system to analyze the early stages of FMDV pentameric capsid
      intermediate assembly and demonstrate a novel requirement for the cellular
      chaperone hsp90 in the formation of these pentameric intermediates. We show the
      added complexity involved for this process to occur, which could be the basis for
      a novel antiviral control mechanism for FMDV.

PMID- 29212946
TI  - The Integrated Stress Response Is Not a Target for Diffuse White Matter Injury in
      Premature Infants.

PMID- 29212944
TI  - The Neutralizing Linear Epitope of Human Herpesvirus 6A Glycoprotein B Does Not
      Affect Virus Infectivity.
AB  - Human herpesvirus 6A (HHV-6A) glycoprotein B (gB) is a glycoprotein consisting of
      830 amino acids and is essential for the growth of the virus. Previously, we
      reported that a neutralizing monoclonal antibody (MAb) called 87-y-13
      specifically reacts with HHV-6A gB, and we identified its epitope residue at
      asparagine (Asn) 347 on gB. In this study, we examined whether the epitope
      recognized by the neutralizing MAb is essential for HHV-6A infection. We
      constructed HHV-6A bacterial artificial chromosome (BAC) genomes harboring
      substitutions at Asn347, namely, HHV-6A BACgB(N347K) and HHV-6A BACgB(N347A).
      These mutant viruses could be reconstituted and propagated in the same manner as
      the wild type and their revertants, and MAb 87-y-13 could not inhibit infection
      by either mutant. In a cell-cell fusion assay, Asn at position 347 on gB was
      found to be nonessential for cell-cell fusion. In addition, in building an HHV-6A
      gB homology model, we found that the epitope of the neutralizing MAb is located
      on domain II of gB and is accessible to solvents. These results indicate that Asn
      at position 347, the linear epitope of the neutralizing MAb, does not affect HHV
      6A infectivity.IMPORTANCE Glycoprotein B (gB) is one of the most conserved
      glycoproteins among all herpesviruses and is a key factor for virus entry.
      Therefore, antibodies targeted to gB may neutralize virus entry. Human
      herpesvirus 6A (HHV-6A) encodes gB, which is translated to a protein of about 830
      amino acids (aa). Using a monoclonal antibody (MAb) for HHV-6A gB, which has a
      neutralizing linear epitope, we analyzed the role of its epitope residue, N347,
      in HHV-6A infectivity. Interestingly, this gB linear epitope residue, N347, was
      not essential for HHV-6A growth. By constructing a homology model of HHV-6A gB,
      we found that N347 was located in the region corresponding to domain II.
      Therefore, with regard to its neutralizing activity against HHV-6A infection, the
      epitope on gB might be exposed to solvents, suggesting that it might be a target
      of the immune system.

PMID- 29212947
TI  - Requirement of Treg-intrinsic CTLA4/PKCeta signaling pathway for suppressing
      tumor immunity.
AB  - The ability of Tregs to control the development of immune responses is essential
      for maintaining immune system homeostasis. However, Tregs also inhibit the
      development of efficient antitumor responses. Here, we explored the
      characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCeta
      signaling pathway that we recently found to be required for contact-dependent
      Treg-mediated suppression. We show that PKCeta is required for the Treg-mediated
      suppression of tumor immunity in vivo. The presence of PKCeta-deficient (Prkch-/
      ) Tregs in the tumor microenvironment was associated with a significantly
      increased expression of the costimulatory molecule CD86 on intratumoral CD103+
      DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of
      effector cytokines produced by these cells. Similar to mouse Tregs, the
      GIT/PAK/PIX complex also operated downstream of CTLA4 and PKCeta in human Tregs,
      and GIT2 knockdown in Tregs promoted antitumor immunity. Collectively, our data
      suggest that targeting the CTLA4/PKCeta/GIT/PAK/PIX signaling pathway in Tregs
      could represent a novel immunotherapeutic strategy to alleviate the negative
      impact of Tregs on antitumor immune responses.

PMID- 29212948
TI  - Elevated urinary CRELD2 is associated with endoplasmic reticulum stress-mediated
      kidney disease.
AB  - ER stress has emerged as a signaling platform underlying the pathogenesis of
      various kidney diseases. Thus, there is an urgent need to develop ER stress
      biomarkers in the incipient stages of ER stress-mediated kidney disease, when a
      kidney biopsy is not yet clinically indicated, for early therapeutic
      intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly
      identified protein that is induced and secreted under ER stress. For the first
      time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive
      urinary biomarker for detecting ER stress in podocytes or renal tubular cells in
      murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin-
      or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most
      importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant
      tubulointerstitial kidney disease caused by UMOD mutations, a prototypical
      tubular ER stress disease. In addition, in pediatric patients undergoing cardiac
      surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly
      associate with severe AKI after surgery. In conclusion, our study has identified
      CRELD2 as a potentially novel urinary ER stress biomarker with potential utility
      in early diagnosis, risk stratification, treatment response monitoring, and
      directing of ER-targeted therapies in selected patient subgroups in the emerging
      era of precision nephrology.

PMID- 29212949
TI  - Early pridopidine treatment improves behavioral and transcriptional deficits in
      YAC128 Huntington disease mice.
AB  - Pridopidine is currently under clinical development for Huntington disease (HD),
      with on-going studies to better characterize its therapeutic benefit and mode of
      action. Pridopidine was administered either prior to the appearance of disease
      phenotypes or in advanced stages of disease in the YAC128 mouse model of HD. In
      the early treatment cohort, animals received 0, 10, or 30 mg/kg pridopidine for a
      period of 10.5 months. In the late treatment cohort, animals were treated for 8
      weeks with 0 mg/kg or an escalating dose of pridopidine (10 to 30 mg/kg over 3
      weeks). Early treatment improved motor coordination and reduced anxiety- and
      depressive-like phenotypes in YAC128 mice, but it did not rescue striatal and
      corpus callosum atrophy. Late treatment, conversely, only improved depressive
      like symptoms. RNA-seq analysis revealed that early pridopidine treatment
      reversed striatal transcriptional deficits, upregulating disease-specific genes
      that are known to be downregulated during HD, a finding that is experimentally
      confirmed herein. This suggests that pridopidine exerts beneficial effects at the
      transcriptional level. Taken together, our findings support continued clinical
      development of pridopidine for HD, particularly in the early stages of disease,
      and provide valuable insight into the potential therapeutic mode of action of
      pridopidine.

PMID- 29212950
TI  - PI3Kalpha inactivation in leptin receptor cells increases leptin sensitivity but
      disrupts growth and reproduction.
AB  - The role of PI3K in leptin physiology has been difficult to determine due to its
      actions downstream of several metabolic cues, including insulin. Here, we used a
      series of mouse models to dissociate the roles of specific PI3K catalytic
      subunits and of insulin receptor (InsR) downstream of leptin signaling. We show
      that disruption of p110alpha and p110beta subunits in leptin receptor cells
      (LRDeltaalpha+beta) produces a lean phenotype associated with increased energy
      expenditure, locomotor activity, and thermogenesis. LRDeltaalpha+beta mice have
      deficient growth and delayed puberty. Single subunit deletion (i.e., p110alpha in
      LRDeltaalpha) resulted in similarly increased energy expenditure, deficient
      growth, and pubertal development, but LRDeltaalpha mice have normal locomotor
      activity and thermogenesis. Blunted PI3K in leptin receptor (LR) cells enhanced
      leptin sensitivity in metabolic regulation due to increased basal hypothalamic
      pAKT, leptin-induced pSTAT3, and decreased PTEN levels. However, these mice are
      unresponsive to leptin's effects on growth and puberty. We further assessed if
      these phenotypes were associated with disruption of insulin signaling.
      LRDeltaInsR mice have no metabolic or growth deficit and show only mild delay in
      pubertal completion. Our findings demonstrate that PI3K in LR cells plays an
      essential role in energy expenditure, growth, and reproduction. These actions are
      independent from insulin signaling.

PMID- 29212951
TI  - Glycolytic requirement for NK cell cytotoxicity and cytomegalovirus control.
AB  - NK cell activation has been shown to be metabolically regulated in vitro;
      however, the role of metabolism during in vivo NK cell responses to infection is
      unknown. We examined the role of glycolysis in NK cell function during murine
      cytomegalovirus (MCMV) infection and the ability of IL-15 to prime NK cells
      during CMV infection. The glucose metabolism inhibitor 2-deoxy-?-glucose (2DG)
      impaired both mouse and human NK cell cytotoxicity following priming in vitro.
      Similarly, MCMV-infected mice treated with 2DG had impaired clearance of NK
      specific targets in vivo, which was associated with higher viral burden and
      susceptibility to infection on the C57BL/6 background. IL-15 priming is known to
      alter NK cell metabolism and metabolic requirements for activation. Treatment
      with the IL-15 superagonist ALT-803 rescued mice from otherwise lethal infection
      in an NK-dependent manner. Consistent with this, treatment of a patient with ALT
      803 for recurrent CMV reactivation after hematopoietic cell transplant was
      associated with clearance of viremia. These studies demonstrate that NK cell
      mediated control of viral infection requires glucose metabolism and that IL-15
      treatment in vivo can reduce this requirement and may be effective as an
      antiviral therapy.

PMID- 29212952
TI  - Dysregulated aldosterone secretion in persons of African descent with endothelin
      1 gene variants.
AB  - Compared with persons of European descent (ED), persons of African descent (AD)
      have lower aldosterone (ALDO) levels, with the assumption being that the
      increased cardiovascular disease (CVD) risk associated with AD is not related to
      ALDO. However, the appropriateness of the ALDO levels for the volume status in AD
      is unclear. We hypothesized that, even though ALDO levels are lower in AD, they
      are inappropriately increased, and therefore, ALDO could mediate the increased
      CVD in AD. To test this hypothesis, we analyzed data from HyperPATH - 1,788
      individuals from the total cohort and 765 restricted to ED-to-AD in a 2:1 match
      and genotyped for the endothelin-1 gene (EDN1). Linear regression analyses with
      adjustments were performed. In the total and restricted cohorts, PRA, ALDO, and
      urinary potassium levels were significantly lower in AD. However, in the AD
      group, greater ALDO dysregulation was present as evidenced by higher ALDO/plasma
      renin activity (PRA) ratios (ARR) and sodium-modulated ALDO suppression-to
      stimulation indices. Furthermore, EDN1 minor allele carriers had significantly
      greater ARRs than noncarriers but only in the AD group. ARR levels were modulated
      by a significant interaction between EDN1 and AD. Thus, EDN1 variants may
      identify particularly susceptible ADs who will be responsive to treatment
      targeting ALDO-dependent pathways (e.g., mineralocorticoid-receptor antagonists).

PMID- 29212953
TI  - The E3 ubiquitin ligase Siah1 regulates adrenal gland organization and
      aldosterone secretion.
AB  - Primary and secondary hypertension are major risk factors for cardiovascular
      disease, the leading cause of death worldwide. Elevated secretion of aldosterone
      resulting from primary aldosteronism (PA) is a key driver of secondary
      hypertension. Here, we report an unexpected role for the ubiquitin ligase Siah1
      in adrenal gland development and PA. Siah1a-/- mice exhibit altered adrenal gland
      morphology, as reflected by a diminished X-zone, enlarged medulla, and
      dysregulated zonation of the glomerulosa as well as increased aldosterone levels
      and aldosterone target gene expression and reduced plasma potassium levels. Genes
      involved in catecholamine biosynthesis and cAMP signaling are upregulated in the
      adrenal glands of Siah1a-/- mice, while genes related to retinoic acid signaling
      and cholesterol biosynthesis are downregulated. Loss of Siah1 leads to increased
      expression of the Siah1 substrate PIAS1, an E3 SUMO protein ligase implicated in
      the suppression of LXR, a key regulator of cholesterol levels in the adrenal
      gland. In addition, SIAH1 sequence variants were identified in patients with PA;
      such variants impaired SIAH1 ubiquitin ligase activity, resulting in elevated
      PIAS1 expression. These data identify a role for the Siah1-PIAS1 axis in adrenal
      gland organization and function and point to possible therapeutic targets for
      hyperaldosteronism.

PMID- 29212956
TI  - ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent
      autoimmune encephalomyelitis.
AB  - Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype
      and functions have been elusive to date. Here, we demonstrate that ICAM1 surface
      expression distinguishes extra- from intravascular neutrophils in the mouse CNS
      during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis
      of these 2 subpopulations indicated that neutrophils, once extravasated, acquire
      macrophage-like properties, including the potential for immunostimulation and MHC
      class II-mediated antigen presentation. In corroboration, super-resolution (3D
      stimulated emission-depletion [STED]) microscopy revealed neutrophils forming
      synapses with T and B cells in situ. Further, neutrophils specifically express
      the aspartic retroviral-like protease ASPRV1, which increases in the CNS during
      EAE and severe cases of multiple sclerosis. Without ASPRV1, mice immunized with a
      new B cell-dependent myelin antigen (but not with the traditional myelin
      oligodendrocyte glycoprotein peptide) develop a chronic phase of EAE that is less
      severe and even completely fades in many individuals. Therefore, ICAM1+
      macrophage-like neutrophils can play both shared and nonredundant roles in
      autoimmune demyelination, among them perpetuating inflammation via ASPRV1.

PMID- 29212957
TI  - Comparison of Glass Capillary Plates and Polyethylene Fiber Bundles as Phantoms
      to Assess the Quality of Diffusion Tensor Imaging.
AB  - PURPOSE: The purpose of this study was to evaluate the suitability of two
      phantoms, one made of capillary plates and the other polyethylene fibers, for
      assessing the quality of diffusion tensor imaging (DTI). METHODS: The first
      phantom was a stack of glass capillary plates with many parallel micropores (CP).
      The second phantom was a bundle of polyethylene fiber Dyneema held together with
      a thermal shrinkage tube (Dy). High resolution multi-shot echo planar imaging
      (EPI) DTI acquisitions were performed at b-values of 0 and 1000 s/mm2 and
      diffusion-times (Tdiff) of 37.7 and 97.7 ms on a preclinical 7T MRI scanner.
      Thirty diffusion-encoding directions were used. The data were used to calculate
      the fractional anisotropy (FA), mean diffusivity (MD), and angular dispersion
      (AD). Further acquisitions were performed at b-values from 0 to 8000 s/mm2 in 14
      steps with the diffusion gradient applied parallel (axial) and perpendicular
      (radial) to the Z direction. On the other hand, the data acquired with a 3T MRI
      scanner were used to confirm that measurements on a clinical machine are
      consistent with the 7T MRI results. RESULTS: The dependence of FA, MD and AD on
      Tdiff was smaller for the Dy than for the CPs. The b-value-dependent signal
      attenuations in the axial direction at Tdiff = 37.7 and 97.7 ms were similar for
      both phantoms. In the radial direction, Dy demonstrated similar b-value
      attenuation to that of in vivo tissue for both Tdiffs, but the attenuation for
      the CPs was affected by the change in Tdiff. Parameter estimates were similar for
      3T and 7T MRI. CONCLUSION: The characteristics of the CP indicate that it can be
      used as a restricted-diffusion dominant phantom, while the characteristics of the
      Dy suggest that it can be used as a hindered-diffusion dominant phantom. Dy may
      be more suitable than CP for DTI quality control.

PMID- 29212955
TI  - Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality
      via acute respiratory distress syndrome.
AB  - Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by
      neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase
      (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we
      hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and
      mortality in subjects with sepsis. In sequential consenting patients with sepsis,
      free 2-ClFA levels were significantly associated with ARDS, and with 30-day
      mortality, for each log increase in free 2-chlorostearic acid. Plasma MPO was not
      associated with either ARDS or 30-day mortality but was correlated with 2-ClFA
      levels. Addition of plasma 2-ClFA levels to the APACHE III score improved
      prediction for ARDS. Plasma 2-ClFA levels correlated with plasma levels of
      angiopoietin-2, E selectin, and soluble thrombomodulin. Endothelial cells treated
      with 2-ClFA responded with increased adhesion molecule surface expression,
      increased angiopoietin-2 release, and dose-dependent endothelial permeability.
      Our results suggest that 2-ClFAs derived from neutrophil MPO-catalyzed oxidation
      contribute to pulmonary endothelial injury and have prognostic utility in sepsis
      associated ARDS.

PMID- 29212954
TI  - Inhibition of AKT signaling uncouples T cell differentiation from expansion for
      receptor-engineered adoptive immunotherapy.
AB  - Adoptive immunotherapies using T cells genetically redirected with a chimeric
      antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical
      practice. Despite encouraging results, some patients do not respond to current
      therapies. In part, this phenomenon has been associated with infusion of reduced
      numbers of early memory T cells. Herein, we report that AKT signaling inhibition
      is compatible with CAR and TCR retroviral transduction of human T cells while
      promoting a CD62L-expressing central memory phenotype. Critically, this
      intervention did not compromise cell yield. Mechanistically, disruption of AKT
      signaling preserved MAPK activation and promoted the intranuclear localization of
      FOXO1, a transcriptional regulator of T cell memory. Consequently, AKT signaling
      inhibition synchronized the transcriptional profile for FOXO1-dependent target
      genes across multiple donors. Expression of an AKT-resistant FOXO1 mutant
      phenocopied the influence of AKT signaling inhibition, while addition of AKT
      signaling inhibition to T cells expressing mutant FOXO1 failed to further augment
      the frequency of CD62L-expressing cells. Finally, treatment of established B cell
      acute lymphoblastic leukemia was superior using anti-CD19 CAR-modified T cells
      transduced and expanded in the presence of an AKT inhibitor compared with
      conventionally grown T cells. Thus, inhibition of signaling along the PI3K/AKT
      axis represents a generalizable strategy to generate large numbers of receptor
      modified T cells with an early memory phenotype and superior antitumor efficacy.

PMID- 29212958
TI  - Estimating Age at Death Based on Costal Cartilage Calcification.
AB  - Age estimation is a crucial part of forensic investigations. Because different
      parts of the body are often found at crime scenes, it is important to explore the
      regions that can be used for age estimation. Previous studies have used simple X
      ray to analyze changes in costal cartilage calcification as a measure of age.
      Here, we tested whether age could be better estimated using measurements of
      costal cartilage calcification on postmortem CT images. In this study, male and
      female decedents (n = 10 each) from autopsy cases were grouped into 10-year
      incremental age groups (20-29 y; 30-39 y; up to 89 y). We found that the mean
      Hounsfield unit (CT number) and percentage calcification (the ratio of the
      ossified area to the whole area) increased with age for both sexes. However,
      there were marked individual differences within many of the groups, and this led
      to a statistically significant difference (P < 0.05) only between the 20-29 y
      group and the older age groups. To improve the ability to correctly assign cases
      to age groups, we introduced and reanalyzed the data using Bayesian statistics.
      This improved the classifications rates, with 40% of males and 35% of females
      correctly assigned into their age groups. Broadening the age range could further
      improve the number of matches. Thus, combining Bayesian statistics with CT
      imaging can be used to estimate age at death from costal cartilage calcification,
      and could be used as an adjunct in forensic investigations.

PMID- 29212959
TI  - Geriatric Nutritional Risk Index Predicts Cardiovascular Events in Patients at
      Risk for Heart Failure.
AB  - BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple and objective
      nutritional assessment tool for elderly patients. Lower GNRI values are
      associated with a worse prognosis in patients with heart failure (HF). However,
      few data are available regarding the prognostic effect of the GNRI value for risk
      stratification in patients at risk for HF.Methods and Results:We retrospectively
      investigated 1,823 consecutive patients at risk for HF (Stage A/B) enrolled in
      the IMPACT-ABI Study. GNRI on admission was calculated as follows: 14.89*serum
      albumin (g/dL)+41.7*body mass index/22. Patients were divided into 2 groups
      according to the median GNRI value (107.1). The study endpoint was a composite of
      cardiovascular (CV) events, including CV death and hospitalization for worsening
      HF. Over a 4.7-year median follow-up, CV events occurred in 130 patients. In the
      Kaplan-Meier analysis, patients with low GNRI (<107.1, n=904) showed worse
      prognoses than those with high GNRI (>=107.1, n=919) (20.2% vs. 12.4%, P<0.001).
      In the multivariable Cox proportional hazards analysis, low GNRI was
      significantly associated with the incidence of CV events (hazard ratio: 1.48, 95%
      confidence interval: 1.02-2.14; P=0.040). CONCLUSIONS: The simple and practical
      assessment of GNRI may be useful for predicting CV events in patients with Stage
      A/B HF.

PMID- 29212960
TI  - Life-Threatening Ventricular Arrhythmia Following Exercise-Induced Vasospastic
      Myocardial Ischemia at the Site of a Myocardial Bridge With Progressive J-Wave
      Manifestation.

PMID- 29212961
TI  - Ubiquitin-proteasome system modulates zygotic genome activation in early mouse
      embryos and influences full-term development.
AB  - Maternal RNA/protein degradation and zygotic genome activation (ZGA), occurring
      during maternal-to-zygotic transition (MZT), are the first essential events for
      the development of pre-implantation embryos. Previously, we have shown the
      importance of the ubiquitin-proteasome system (UPS) for initiation of minor ZGA
      at the 1-cell stage of mouse embryos. However, little is known about the
      mechanism of involvement of the UPS-degraded maternal proteins in ZGA. In this
      study, we investigated the effect of inhibiting maternal protein degradation by
      the reversible proteasome inhibitor, MG132, on post-implantation development and
      ZGA regulation during early cleavage stages. Our study revealed that zygotic
      transcription by RNA polymerase II (Pol II) at the 1-cell stage was delayed and
      the full-term development was affected by transient proteasome inhibition during
      1 to 9 h post-insemination (hpi). Furthermore, we found that the transient
      inhibition of proteasome activity at the 2-cell stage delayed the onset of
      transcription of some major ZGA genes. These results support the model
      hypothesizing the requirement of sequential degradation of maternal proteins by
      UPS for the proper onset of ZGA and normal progression of MZT in early mouse
      embryos.

PMID- 29212963
TI  - Association Between Elevated Echocardiographic Index of Left Ventricular Filling
      Pressure and Acute Kidney Injury After Off-Pump Coronary Artery Surgery.
AB  - BACKGROUND: The ratio of the early transmitral flow velocity to early diastolic
      velocity of the mitral annulus (E/e') is an echocardiographic index of mean left
      ventricular (LV) filling pressure. We investigated the association between the
      preoperative E/e' ratio and postoperative acute kidney injury (AKI) during off
      pump coronary artery bypass surgery (OPCAB).Methods and Results:We reviewed 585
      patients who underwent OPCAB and with preserved LV ejection fraction determined
      by preoperative echocardiography. AKI was determined by the Kidney Disease
      Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression
      analysis was performed. E/e' was also analyzed as 3 categories (E/e' <8,
      8<=E/e'<=15, and E/e' >15) and as a continuous variable. A propensity score
      analysis was used to match the patients with E/e' >15 and E/e' <=15. A
      preoperative E/e' >15 was an independent predictor for AKI (odds ratio 3.01, 95%
      confidence interval 1.40-6.17). E/e' >15 was also an independent predictor for
      AKI when E/e' was analyzed with 3 categories or as a continuous variable. In the
      matched sample, the incidence of AKI and 1-year mortality was significantly
      higher in patients with E/e' >15. CONCLUSIONS: Among patients undergoing OPCAB
      with preserved LV systolic function, a preoperative E/e' ratio >15 was an
      independent predictor of postoperative AKI. Measurement of the preoperative E/e'
      ratio may help to assess the risk of postoperative AKI.

PMID- 29212962
TI  - Effects of insulin-like growth factor-1 on the in vitro maturation of canine
      oocytes.
AB  - The maturation rate of canine oocytes during in vitro maturation (IVM) needs to
      be improved. The present study was designed to evaluate the effects of insulin
      like growth factor-1 (IGF-1) on the IVM of canine oocytes. Ovaries were obtained
      by ovariohysterectomy and were sliced to release cumulus-oocyte complexes (COCs).
      In Experiment 1, the effects of different concentrations of IGF-1 on the nuclear
      maturation of oocytes was investigated. The COCs were cultured in a modified
      medium (mTCM199) with IGF-1 (0, 0.5, 5, 10, and 50 ug/ml). At the end of the 48 h
      culture, oocytes were fixed and stained to evaluate their nuclear stage.
      Supplementation with 50 ug/ml IGF-1 induced a significantly higher metaphase II
      (MII) rate (P < 0.05) compared to the 0 and 0.5 MUg/ml IGF-1 groups. In
      Experiment 2, the expression levels of insulin receptor (INSR), IGF-1 receptor
      (IGF-1R), and IGF-2 receptor (IGF-2R) genes, localized to canine oocytes and
      cumulus cells, were investigated before and after IVM. The expression level of
      IGF-1R in cumulus cells after IVM was higher than that before IVM (P < 0.05). In
      Experiment 3, it was investigated whether an inhibitor of PTEN (phosphatase and
      tensin homolog), bpV, affects the nuclear maturation of oocytes. Regardless of
      bpV supplementation at a concentration of 0.2 to 200 umol/l, there was no
      significant difference in the proportion of oocytes that reached the MII stage.
      These results indicated that IGF-1 has a favorable effect on the IVM of canine
      oocytes, possibly through the stimulation of the Ras/MAPK pathway via IGF-1R
      expressed in cumulus cells.

PMID- 29212964
TI  - Simple Determination of Plasma Ponatinib Concentration Using HPLC.
AB  - Ponatinib, a novel tyrosine kinase inhibitor marketed in 2016, is a key drug used
      for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute
      lymphoblastic leukemia. This study aimed to develop a simple method for
      determining plasma ponatinib concentration. The analysis required extraction of a
      400-uL sample of plasma and precipitation of proteins using an Oasis HLB
      cartridge. Ponatinib and bosutinib, which is used as an internal standard, were
      separated by HPLC using a mobile phase of acetonitrile : 0.037 mol/L KH2PO4 (pH
      4.5) (39 : 61, v/v) on a Capcell Pack C18 MG II (25*4.6 mm) monitored at 250 nm,
      with a flow rate of 1.0 mL/min. This assay method was then used for determining
      plasma ponatinib concentration in a 42-year-old man treated with ponatinib at 15
      mg/d. The calibration curve was found to be linear for the plasma concentration
      range of 5-250 ng/mL with a regression coefficient (r2) of 0.9999. The
      coefficients of intra-day and inter-day validation under these concentrations
      were 2.1-6.0 and 4.5-8.0%, respectively. The assay accuracy was -1.5-9.0%, and
      the recovery was greater than 86%. The plasma concentration of the patient at 2.5
      and 3 h after 15 mg ponatinib administration was 43.6 and 49.3 ng/mL,
      respectively. This method of HPLC equipped with UV detection for determining
      plasma ponatinib concentration has several advantages, such as simplicity and
      applicability to routine therapeutic drug monitoring at hospital laboratories.

PMID- 29212965
TI  - Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in
      Acute Coronary Syndrome.
AB  - BACKGROUND: The results of previous clinical trials on the effects of ezetimibe
      statin combination therapy on atherosclerosis are inconsistent, and the anti
      atherosclerotic effect of ezetimibe remains controversial.Methods and Results:We
      conducted a prospective, randomized open-label study at 10 centers. One hundred
      and twenty-eight statin-naive patients with acute coronary syndrome (ACS)
      undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary
      intervention were randomized to receive either 2 mg/day pitavastatin plus 10
      mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had
      evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The
      primary endpoint was the percentage change in non-culprit coronary plaque volume
      (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein
      cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy
      group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n=53; between
      group difference, 16.9%, P<0.0001). The percent change in PV was -5.1% in the
      combination therapy group and -6.2% in the statin alone group (P=0.66), although
      both groups had reduction of PV compared with baseline (both P<0.01). The percent
      change in lipid PV did not differ between the groups (4.3 vs. -3.0%, P=0.37).
      CONCLUSIONS: In statin-naive patients with ACS, combined therapy with ezetimibe
      and statin did not result in a significant change in coronary plaque regression
      or tissue component compared with statin alone. [Clinical Trial Registration:
      www.clinicaltrials.gov (NCT00549926)].

PMID- 29212966
TI  - Know Me! Unraveling the Riddle of Calcific Aortic Valve Disease by
      Bioinformatics.

PMID- 29212968
TI  - ?

PMID- 29212967
TI  - Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic
      Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling.
AB  - In our aging world, increasing numbers of people are suffering from calcific
      aortic valve disease (CAVD). In this study, we used integrated bioinformatics
      analysis to predict several key genes that are involved in the initiation and
      progression of CAVD. Expression profiles of 15 calcific and 14 normal human
      aortic valve samples were generated from two gene expression datasets (GSE12644
      and GSE51472). Dataset GSE26953 from the human aortic valve fibrosa-derived
      endothelial cells cultured under laminar or oscillatory shear stress was also
      evaluated. Related R packages were used to process the data. Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses
      were performed for functional annotation. Hub genes were identified based on the
      protein-protein interaction network. CAVD-related gene modules were identified by
      Weighted Gene Co-expression Network Analysis (WGCNA). The predicted key genes
      were manually reviewed. In our present work, complex connections among mechano
      response, oxidative stress, inflammation and extracellular remodeling pathways in
      the etiology of CAVD were revealed. The key genes, thus identified, encode a
      transcription factor KLF2 and phospholipid phosphatase 3 (PLPP3) that are
      involved in mechano-responses; eNOS involved in oxidative stress; IL-8 involved
      in inflammation; and collagen triple helix repeat containing 1 (CTHRC1) and
      secretogranin II (SCG2) involved in extracellular remodeling. These gene products
      are predicted to play critical roles in CAVD development and progression. The
      present study provides valuable information for future research and drug
      development.

PMID- 29212969
TI  - [Analysis of long-term survivors with cardiac AL amyloidosis].
AB  - Cardiac AL amyloidosis (CA) is generally known as a severe disease with very poor
      prognosis. Here we retrospectively examined seven patients with CA in our cohort
      who achieved long-term survival. All six patients who underwent high-dose
      melphalan and autologous stem cell transplantation (ASCT) survived for >3 years,
      whereas four patients survived for >5 years. Patients who underwent ASCT had
      prompt hematological responses, and five patients showed organ responses. ASCT
      helps to achieve a quick and deep hematological response required for long-term
      survival in patients with CA. New agents have been implemented for the treatment
      of CA. However, the risks and benefits of each treatment modality should be
      considered according to patient condition, thus making the best use of ASCT in
      combination with new agents for the treatment of CA.

PMID- 29212970
TI  - [Prior harvesting and cryopreservation of peripheral blood stem cells from
      related donors: current situations in Japan].
AB  - Although peripheral blood stem cell (PBSC) transplantations in an unrelated
      transplant setting have been performed since 2010, prior harvesting and
      cryopreservation of PBSCs from unrelated donors has not been approved in Japan.
      There are no restrictions with regard to related donors. Therefore, in April
      2015, we conducted a nationwide survey and obtained written answers from 123
      transplant hospitals throughout Japan. Our survey revealed that as much as 81.3%
      of transplant hospitals routinely perform prior harvesting and cryopreservation
      of PBSCs from related donors and that both cell processing and quality management
      of cryopreserved products have been appropriately conducted in line with domestic
      guidelines, although post-thaw quality control and storage period setting require
      further improvements. Moreover, informed consent obtained from both patients and
      donors with regard to cryopreservation of PBSCs was not always sufficient in some
      hospitals. We found that the average number of unused or discarded cryopreserved
      PBSCs is 1.09 per hospital, and the overall nonuse or discard rates of
      cryopreserved PBSCs were estimated to be as low as 2.67%.

PMID- 29212971
TI  - [Chronic myeloid leukemia complicated by pulmonary hypertension during dasatinib
      therapy: a single-center retrospective study].
AB  - Pulmonary artery hypertension (PAH) has been reported to be a severe adverse
      event associated with dasatinib therapy. Among the 76 chronic myeloid patients
      who were treated with dasatinib at our hospital, six patients showed high
      estimated pulmonary arterial systolic pressure, as observed by echocardiography.
      PAH was confirmed using right heart catheterization in three (3.9%) patients with
      increased mean pulmonary artery pressure (mPAP). In one patient, although mPAP
      was higher than the normal range, it did not fulfill the criteria of pulmonary
      hypertension. After the discontinuation of dasatinib, BNP and dyspnea were
      improved in five patients. Therefore, it should be noted that dasatinib can cause
      PAH at higher rates than those reported previously, and if PAH is confirmed or
      suspected during dasatinib therapy, then dasatinib should be immediately
      discontinued.

PMID- 29212972
TI  - [Lenalidomide and low-dose dexamethasone therapy for Japanese patients with newly
      diagnosed multiple myeloma: updated results of the MM-025 study].
AB  - In a Japanese phase II study (MM-025), the efficacy and safety of lenalidomide
      plus low-dose dexamethasone (Rd) were confirmed at a median follow-up of 14.2
      months in patients with newly diagnosed multiple myeloma who were ineligible for
      hematopoietic stem cell transplantation. In the present report, we analyzed the
      follow-up data from the abovementioned study. Treatment was stopped for all 26
      patients after a median follow-up of 31.3 months, and the median treatment
      duration was approximately 25 months. The overall response rate was 87.5%, and
      the complete response rate was 20.8%. The median duration of response and
      progression-free survival were 30.7 and 31.6 months, respectively. The median
      overall survival has not yet been reached. At least one grade 3/4 adverse event
      was experienced by 23 patients (88.5%), and 18 patients (69.2%) experienced
      serious adverse events. There were no treatment-related deaths. Therefore, the
      efficacy and safety of Rd were confirmed in transplant-ineligible Japanese
      patients with newly diagnosed multiple myeloma at the present follow-up period.

PMID- 29212973
TI  - [Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20
      expression after rituximab therapy and gain of CD20 expression after
      administration of vorinostat and gemcitabine].
AB  - A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node
      biopsy revealed effacement of the normal nodal architecture with diffuse
      proliferation of medium-sized atypical lymphoid cells. Southern blot analyses
      demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin
      heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma
      (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP,
      he relapse occurred after 2 months. CD20-negative conversion was confirmed in the
      lymph node, which was positive for CCR4, and the skin at the time of relapse. The
      patient received the GDP regimen as salvage therapy with the addition of
      vorinostat for skin involvement; however, he failed to respond, and the disease
      systemically progressed. Furthermore, he also exhibited progression in the skin
      after stopping vorinostat due to hematologic toxicity. A lymph node biopsy at
      progression revealed CD20 re-expression by immunohistochemistry. At progression,
      the patient received mogamulizumab but failed to respond, and he died owing to
      disease progression 8 months after relapse. In this case, we demonstrated CD20
      negative conversion following rituximab and CD20-positive reversion after using
      vorinostat and gemcitabine.

PMID- 29212974
TI  - [IgE-kappa type multiple myeloma achieving complete response with novel agents].
AB  - IgE multiple myeloma (MM) is a rare subtype of MM characterized by an aggressive
      and poor prognosis. Although novel agents have improved the prognosis of MM,
      there are few case reports of IgE MM treated with these agents. A 53-year-old
      male patient presented with pain in the right rib and was diagnosed with IgE
      kappa MM. He was treated with multidrug chemotherapy, including bortezomib and
      lenalidomide, and underwent autologous stem-cell transplantation (ASCT). Finally,
      he achieved a complete response after the initiation of pomalidomide. In previous
      reports, majority of patients with refractory IgE MM treated with novel agents
      had a poor prognosis. In contrast, patients who were treated with novel agents
      from the beginning and underwent ASCT had a long-term survival. Overall, the use
      of novel agents as the first-line therapy is expected to improve IgE MM
      prognosis.

PMID- 29212975
TI  - [Diffuse large B-cell lymphoma complicated with drug-induced vasculitis during
      administration of pegfilgrastim].
AB  - A 59-year-old female with diffuse large B-cell lymphoma was treated with
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP)
      regimen. In addition, we administered pegfilgrastim for treating chemotherapy
      induced febrile neutropenia. She complained of fever and neck and chest pain a
      few days after pegfilgrastim administration during the third and fourth courses
      of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which
      led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis
      observed in this case was caused by pegfilgrastim administration because similar
      symptoms appeared with both injections of pegfilgrastim.

PMID- 29212976
TI  - [Congenital leukemia showing lineage switch following induction chemotherapy and
      attaining long-term remission after HLA-haploidentical stem cell
      transplantation].
AB  - Congenital leukemia is a rare subgroup of childhood leukemia. Lineage switches in
      leukemic cells are relatively rare events, which have been occasionally reported
      in congenital leukemia. To the best of our knowledge, the survival of congenital
      leukemia patients with lineage switch has not been previously documented. This
      lack of documentation may be attributable to extremely poor prognosis of these
      patients. We describe a case of a newborn female with initial diagnosis of MLL
      AF4 positive B-precursor acute lymphoblastic leukemia, who developed lineage
      switch to acute monocytic leukemia following the induction therapy. Although
      morphological remission was temporary, she received an HLA-haploidentical bone
      marrow transplant from her father with non-remission status because of an early
      relapse at the age of 4 months. Despite many difficulties such as graft-versus
      host disease, growth impairment, and psychomotor retardation, she remained in
      remission for 3 years and 7 months after the transplant. This successful outcome
      suggests that the graft-versus-leukemia effect was potentially accomplished in
      the patient. Taken together, early HLA-haploidentical stem cell transplant
      following remission is required for congenital leukemia patients with lineage
      switch, and it may be an effective alternative for refractory patients.

PMID- 29212977
TI  - [Philadelphia chromosome-positive acute lymphoblastic leukemia complicated by
      concomitant Achromobacter xylosoxidans and Corynebacterium striatum bacteremia
      following allogeneic hematopoietic stem cell transplantation].
AB  - A 54-year-old woman with Philadelphia chromosome-positive acute lymphoblastic
      leukemia (Ph+ALL) underwent hematopoietic stem cell transplantation from an HLA
      matched sibling. Subsequently, she suffered from chronic graft versus host
      disease (GvHD) and received medical treatment. Fever developed on day 697 and
      resulted in a shock state at 10 h after the visit. Achromobacter xylosoxidans was
      detected in the initial blood culture on day 699. General conditions exacerbated
      even after the start of meropenem hydrate (MEPM, Meropen(r)) administration, with
      Corynebacterium striatum detected as an additional species in the initial blood
      culture on day 701. Although vancomycin hydrochloride (VCM, Vancomycin(r)) was
      administered, the conditions did not improve. She died on day 702. Between
      January 2012 and December 2016, A. xylosoxidans was detected only in nine cases
      in our hospital, which included five with hematological malignancies and only one
      (present) with sepsis. At the same time, Corynebacterium species were detected in
      blood cultures from 39 cases in our hospital, which included 31 with
      hematological malignancies. Some reports on drug-resistant A. xylosoxidans and C.
      striatum have been published. Infections with these species may become fatal when
      complicated by sepsis in immunocompromised patients with hematological
      malignancies. More cases should be accumulated for detailed investigation.

PMID- 29212978
TI  - [Acute myeloid leukemia complicated by pneumonia and vertebral osteomyelitis
      during induction chemotherapy].
AB  - A 76-year-old woman was operated on for rectal cancer in 2011 without
      chemotherapy and was followed up in the outpatient department. Decrease in white
      blood cell count was observed from 2013, and she developed anemia in 2015. Bone
      marrow aspiration was performed, and she was diagnosed with acute myeloid
      leukemia with myelodysplasia-related changes (AML/MRC). First, remission
      induction therapy was initiated with idarubicin and cytarabine administration,
      but pneumonia and vertebral osteomyelitis developed during the neutropenic
      period. Although the progress of antibiotics aided in the improvement of the
      recent prognosis of vertebral osteomyelitis compared with the past, poor
      prognosis with high death rate was still inevitable. Then, consolidation therapy
      was initiated with azacitidine (AZA) administration, and treatment was carried
      out for vertebral osteomyelitis with several antibiotics in parallel, which
      together led to the successful treatment of vertebral osteomyelitis while
      maintaining a remission state of AML. Because AZA is known to be well-tolerated
      and neutropenic phase is shorter than intensive chemotherapy in general, it can
      be an effective treatment option for patients who need both infection control and
      AML treatment.

PMID- 29212979
TI  - [Clinical features and quality of life assessment in Japanese PNH patients
      enrolled in the International PNH Registry].
AB  - The aim of the present study was to clarify the clinical characteristics and
      quality of life (QOL) of Japanese patients (N=116) enrolled in the International
      PNH Registry, compared to the whole registry cohort (N=3,457), censored as of
      March 2015. The proportion of patients treated with eculizumab was comparable
      between the two cohorts; the Japanese cohort showed higher levels of lactate
      dehydrogenase and lower hemoglobin values at baseline. Compared to the whole
      cohort, the Japanese cohort had a greater incidence of bone marrow failure (67.4%
      vs 56.8%), but fewer episodes of thrombotic events in their medical history (6.4%
      vs 13.3%), and lower reported rates of abdominal pain (11.9% vs 33.9%), dysphagia
      (1.7% vs 16.4%), and erectile dysfunction (5.6% vs 25.3%). Additionally,
      assessment of QOL using FACIT-Fatigue and EORTC QLQ-C30 confirmed that the
      Japanese cohort had better QOL scores in most of the QOL subscales at baseline.
      These data are the first report of QOL outcomes for the Japanese cohort in the
      International PNH Registry; further assessments are ongoing.

PMID- 29212980
TI  - ?

PMID- 29212981
TI  - ?

PMID- 29212982
TI  - ?

PMID- 29212983
TI  - ?

PMID- 29212984
TI  - [Erratum].

PMID- 29212985
TI  - Bone Formation Parameters of the Biopsied Ilium Differ between Subtrochanteric
      and Diaphyseal Atypical Femoral Fractures in Bisphosphonate-Treated Patients.
AB  - Atypical femoral fractures (AFFs) are defined as atraumatic or low-trauma
      fractures located in the subtrochanteric or diaphyseal sites. Long-term
      bisphosphonates (BPs) are administered to prevent fragility fractures in patients
      with primary osteoporosis or collagen diseases who are already taking
      glucocorticoids (GCs). Long-term BP use is one of the most important risk factors
      for AFFs. Its pathogenesis is characterized by severely suppressed bone turnover
      (SSBT), but whether the characteristics of patients are different regarding to
      location of fracture site remains unknown. In this study, we compared the
      characteristics and bone histomorphometric findings between subtrochanteric and
      diaphyseal sites in patients with BP-associated AFFs. Nine women with BP
      associated AFFs were recruited, including 3 with systemic lupus erythematosus, 2
      with rheumatoid arthritis, 2 with primary osteoporosis, 1 with polymyalgia
      rheumatica, and 1 with sarcoidosis. Patients were divided into the
      subtrochanteric group (n = 5; average age, 52 years; BP treatment, 5.9 years) and
      the diaphyseal group (n = 4; average age, 77 years; BP treatment, 2.6 years).
      Compared with the diaphyseal group, the subtrochanteric group had significantly
      higher daily GC doses (average, 10.9 vs. 2.3 mg/day) and significantly lower
      serum 25-hydroxyvitamin-D levels (17.8 vs. 25.6 ng/mL). Bone histomorphometry of
      the biopsied iliac bone showed SSBT in 3 cases (subtrochanteric, n = 1;
      diaphyseal, n = 2). Osteoid volume and trabecular thickness were significantly
      lower in the subtrochanteric group than in the diaphyseal group. Bone formation
      was inhibited more severely in subtrochanteric than in the diaphyseal group due
      to the higher GC doses used.

PMID- 29212986
TI  - Effect of PEAR1 Genetic Variants on 1-Year Outcomes in Chinese Patients with
      Acute Myocardial Infarction After Percutaneous Coronary Intervention.
AB  - AIMS: Platelet endothelial aggregation receptor-1 (PEAR1) is a platelet
      transmembrane protein that plays an important role on platelet aggregation. The
      aim of this study was to investigate whether PEAR1 genetic variations are
      associated with 1-year outcomes in Chinese patients with acute myocardial
      infarction after percutaneous coronary intervention. METHODS: A total of 647
      consecutive Chinese patients with acute myocardial infarction that underwent
      percutaneous coronary intervention and that were exposed to standard dual
      antiplatelet therapy with aspirin and clopidogrel were enrolled in this study.
      Six single nucleotide polymorphisms of PEAR1 were detected using the ligase
      detection reaction method. The follow-up period was 12 months. RESULTS: Overall,
      66 (10.2%) adverse ischemic events occurred. Multivariate Cox regression analysis
      showed that carriage of the PEAR1 rs56260937 minor allele was an independent
      predictor of revascularization events (OR=2.15, 95% CI 1.12-4.15, p=0.022) after
      adjusting for confounding factors. CONCLUSIONS: Genetic testing for PEAR1
      variants can be helpful in predicting adverse ischemic events in Chinese patients
      with acute myocardial infarction after percutaneous coronary intervention.

PMID- 29212988
TI  - New development of research on personal protective equipment (PPE) for
      occupational safety and health.

PMID- 29212987
TI  - Association of Coronary Artery Calcification with Estimated Coronary Heart
      Disease Risk from Prediction Models in a Community-Based Sample of Japanese Men:
      The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).
AB  - AIM: The clinical significance of coronary artery calcification (CAC) is not
      fully determined in general East Asian populations where background coronary
      heart disease (CHD) is less common than in USA/Western countries. We cross
      sectionally assessed the association between CAC and estimated CHD risk as well
      as each major risk factor in general Japanese men. METHODS: Participants were 996
      randomly selected Japanese men aged 40-79 y, free of stroke, myocardial
      infarction, or revascularization. We examined an independent relationship between
      each risk factor used in prediction models and CAC score >=100 by logistic
      regression. We then divided the participants into quintiles of estimated CHD risk
      per prediction model to calculate odds ratio of having CAC score >=100. Receiver
      operating characteristic curve and c-index were used to examine discriminative
      ability of prevalent CAC for each prediction model. RESULTS: Age, smoking status,
      and systolic blood pressure were significantly associated with CAC score >=100 in
      the multivariable analysis. The odds of having CAC score >=100 were higher for
      those in higher quintiles in all prediction models (p-values for trend across
      quintiles <0.0001 for all models). All prediction models showed fair and similar
      discriminative abilities to detect CAC score >=100, with similar c-statistics
      (around 0.70). CONCLUSIONS: In a community-based sample of Japanese men free of
      CHD and stroke, CAC score >=100 was significantly associated with higher
      estimated CHD risk by prediction models. This finding supports the potential
      utility of CAC as a biomarker for CHD in a general Japanese male population.

PMID- 29212989
TI  - [Challenges in community medicine].

PMID- 29212990
TI  - [What to learn from the Patient-Centered Medical Home].

PMID- 29212991
TI  - [Stroke of the elderly].

PMID- 29212992
TI  - [Current picture of cerebral hemorrhage in the elderly].

PMID- 29212994
TI  - [Risk factor control for preventing stroke].

PMID- 29212993
TI  - [Vascular dementia in the elderly].

PMID- 29212995
TI  - [State of glycemic control in elderly diabetic patients].
AB  - AIM: The Japan Diabetes Society and The Japan Geriatric Society made a joint
      committee and published a new glycemic target in May 2016. Because reports on the
      state of glycemic control in elderly diabetic patients are insufficient, we
      investigated the state of glycemic control in this population before the new
      glycemic target was established. METHODS: We enrolled patients older than 65
      years of age who had been prescribed antidiabetic drugs and hospitalized in the
      geriatric department of Nagoya University Hospital from April 1, 2015, to March
      31, 2016. We investigated the participants' HbA1c, prescription of antidiabetic
      drugs carrying risks of severe hypoglycemia (risk drugs) at hospitalization,
      cognitive function, basic activities of daily living, and instrumental activities
      of daily living. RESULTS: A total of 63 patients were enrolled. Thirty-five
      patients were male, the mean age was 83.1+/-5.9 years old, and the average HbA1c
      was 7.6%+/-1.5%. The numbers of patients assigned to categories I, II, and III
      were 10, 12, and 41, respectively. For prescription of risk drugs, 6 participants
      were assigned to category I, 8 to category II, and 22 to category III.
      Prescription of risk drugs was associated with the HbA1c. Approximately one third
      of the patients using risk drugs had a lower HbA1c than the target value.
      CONCLUSIONS: Risk drugs was not significantly associated with the established
      categories or age. Many of the patients who were prescribed risk drugs had a
      lower HbA1c than the target values.

PMID- 29212996
TI  - [A comparison of the associations of dynapenia and sarcopenia with fear of
      falling in elderly diabetic patients].
AB  - AIM: To comparatively investigate whether dynapenia and sarcopenia, as defined by
      the Asian Working Group for Sarcopenia (AWGS), are associated with fear of
      falling in elderly patients with diabetes. METHODS: The subjects were outpatients
      with diabetes who were at least 65 years of age when they visited our hospital.
      Sarcopenia was evaluated based on the AWGS definition. The cutoff values for the
      appendicular skeletal mass index (multi-frequency bioelectrical impedance
      method), grip strength, and walking speed were, respectively, 7.0 kg/m2 for men
      and 5.7 kg/m2 for women, 26 kg for men and 18 kg for women, and <=0.8 m/s for
      both men and women. Those with grip strength of less than or equal to the cutoff
      value were considered to have dynapenia. Fear of falling was assessed by a self
      administered questionnaire survey with the Fall Efficacy Scale (FES) Japanese
      version. A multiple regression analysis was conducted using the FES score as a
      dependent variable and dynapenia or sarcopenia and moderators as explanatory
      variables. RESULTS: A total of 202 patients (male, n=127; female, n=75) were
      analyzed in this study. The FES scores of the patients with and without
      sarcopenia did not differ to a statistically significant extent in either male or
      female patients. The multiple regression analysis revealed a statistically
      significant association between dynapenia and the FES score in men (P=0.028).
      CONCLUSIONS: In elderly outpatients with diabetes, no association was found
      between sarcopenia and the fear of falling in either men or women. In contrast, a
      statistically significant association was found between dynapenia and fear of
      falling in men. This suggests the importance paying attention to the fear of
      falling when examining elderly male diabetes patients with dynapenia.

PMID- 29212997
TI  - [The effects of pain coping skills training among older outpatients with
      osteoarthritis].
AB  - AIM: The present study examined the effects of individual pain coping-skills
      training (PCST) on knee pain, pain coping strategies, physical functions, and
      daily physical activity among older outpatients with osteoarthritis. METHODS:
      Twenty-five older adults who suffered from knee pain and had been diagnosed to
      have knee osteoarthritis (men: n=4; 75.4+/-6.3 years) were assigned to either a
      PCST group (n=13) or a general health education group (n=12) according to their
      wishes. Both groups attended 20-minutes sessions once a week for 8 weeks. At the
      baseline, the basic attributes (e.g. gender, age, duration of knee pain, and
      medical history), BMI, and the severity of knee osteoarthritis were obtained.
      Additionally, knee pain and limitations in mobility, pain coping strategies, pain
      self-efficacy, exercise self-efficacy, lower muscle strength, mobility,
      accelerometer -based time spent in physical activity and sedentary behavior were
      assessed before and after the 8-week intervention period. Analyses were performed
      using an intention-to-treat principle. Differences in each variable between the
      groups were examined using an analysis of covariance. Each participant's baseline
      value was used as the covariate. RESULTS: Even after controlling for the baseline
      attributes and values, only the PCST group exhibited a significant improvement in
      pain self-efficacy (p=0.005), exercise self-efficacy (p=0.042), lower muscle
      strength (p=0.004) and mobility (p=0.027). Furthermore, the PCST showed a
      significant increase in moderate-to vigorous-intensity physical activity
      (p=0.052) and a decrease in medical behaviors as one of pain coping strategies
      (p=0.073). CONCLUSION: The present study showed that PCST therefore appears to be
      a feasible and effective therapeutic strategy which improves self-efficacy for
      controlling knee pain, which may also result in increasing the self-efficacy for
      exercise, physical functions, and daily physical activities.

PMID- 29212998
TI  - [Spontaneous regression of lung cancer in an elderly patient: a case report].
AB  - An 82 year-old male was referred to us because of a nodule in the upper lobe of
      his right lung, which was incidentally found by computed tomography (CT) carried
      out in the course of treating pneumonia. The nodule was identified as non
      keratinizing squamous cell carcinoma of the lung by bronchoscopy. A close
      investigation revealed the tumor to be cT1bN3M1b, clinical Stage IV. Although we
      only adopted a wait-and-see approach because of his age and his suspected
      myelodysplastic syndrome, the nodule had regressed on CT images after a year.
      Fluorodeoxyglucose-positron emission tomography showed apparently decreased
      uptakes in the lymph nodes and adrenal gland. We considered this to be a systemic
      observation of spontaneous regression of carcinoma.

PMID- 29212999
TI  - [A case of hyperammonemia resulting from urinary tract infection caused by urease
      producing bacteria in a Parkinson's disease patient with drug-induced urinary
      retention].
AB  - A 71-year-old woman with a 9-year history of Parkinson's disease was admitted to
      our hospital emergently because of consciousness disturbance. Her consciousness
      level was 200 on the Japan coma scale (JCS), and she presented with tenderness
      and distension of the lower abdomen. Brain computed tomography showed normal
      findings. Blood tests showed an increased ammonia level (209 MUg/dl) with normal
      AST and ALT levels. We catheterized the bladder for urinary retention. Five hours
      after admission, the blood ammonia level decreased to 38 MUg/dl, and her
      consciousness level improved dramatically. Corynebacterium urearyticum, a
      bacterial species that produces urease, was detected by urine culture. Therefore,
      she was diagnosed with hyperammonemic encephalopathy resulting from urinary tract
      infection caused by urease-producing bacteria. In this case, urologic active
      agents had been administered to treat neurogenic bladder. We suspect that these
      drugs caused urinary obstruction and urinary tract infection. It is important to
      recognize that obstructive urinary tract infection caused by urease-producing
      bacteria can cause hyperammonemia. Neurological disorders, such as Parkinson's
      disease, tend to complicate neurogenic bladder. This disease should be considered
      in elderly patients with Parkinson's disease who are receiving urologic active
      drugs.

PMID- 29213000
TI  - [A methotrexate-associated lympholiferative disorder patient with
      gastrointestinal perforation].
AB  - A 70-year-old woman was diagnosed with chronic rheumatoid arthritis and treated
      with methotrexate and prednisolone. She visited our hospital to determine the
      cause of her continuous fatigue and fever for the past three weeks. She consumed
      no food orally and was provided antibiotics because free air was found on
      computed tomography (CT). Intraperitoneal small lymphadenopathy and swelling of
      both adrenal glands was also found on CT, and MTX-associated lymphoproliferative
      disorder (MTX-LPD) was suspected. Am adrenal gland biopsy showed diffuse large B
      cell lymphoma (DLBCL) associated with MTX-LPD. The causes of gastrointestinal
      perforation with collagen diseases have been reported to be functional
      gastrointestinal disorders with collagen diseases like amyloidosis,
      gastrointestinal infections in immunocompromised patients, and side effects of
      medication, such as steroids or NSAIDs and MTX. MTX-LPD is an uncommon side
      effect of methotrexate. To ensure its appropriate diagnosis and treatment, it is
      important to improve the degree of recognition of MTX-LPD, and a prompt response
      is needed.

PMID- 29213002
TI  - [Proceedings of Regional Meeting of the Japan Geriatrics Society].

PMID- 29213001
TI  - [Resumption of enteral nutrition using enteral formula containing sodium alginate
      following hemorrhaging after endoscopic sphincterotomy: a case report].
AB  - Enteral nutrition is often performed in elderly patients with dysphagia.
      Choledocholithiasis is a disease that is common in elderly patients.
      Gastrointestinal hemorrhaging can occur in association with endoscopic
      sphincterotomy, and subsequent enteral nutrition must be carefully resumed. We
      herein report our experience using Mermed Plus containing sodium alginate after
      endoscopic hemostasis. The patient was an 88-year-old woman with an onset of
      gallstone cholangitis during rehabilitation after cerebral infarction. On day 2,
      endoscopic sphincterotomy and biliary drainage were performed, and the
      cholangitis was ameliorated. The degree of arousal and swallowing function were
      unstable, and a liquid diet via the nasogastric tube was initiated from day 6.
      Anemia progressed on day 7, and melena was observed; as a result, the intravenous
      administration of a proton pump inhibitor was initiated. On day 8, endoscopic
      hemostasis of the ulcer proximal to the papilla was performed. From day 10, we
      focused on the mucosal protective effects of sodium alginate, and Mermed Plus was
      initiated. No recurrence of hemorrhaging was observed. On day 13, the endoscopic
      findings revealed that the vicinity of the papilla was covered with solidified
      liquid diet, and the ulcer had healed. The postoperative course was uneventful,
      and swallowing training and rehabilitation were performed. On day 26, oral
      ingestion became possible. Many patients seem to be at risk of developing a
      gastrointestinal mucosal disorder when receiving enteral nutrition. In such
      cases, a liquid diet containing sodium alginate as dietary fiber is easy to use
      and may be useful for resuming enteral nutrition without delay.

PMID- 29213004
TI  - [Notice].

PMID- 29213003
TI  - [Information].

PMID- 29213005
TI  - [Table of Contents].

PMID- 29213006
TI  - [Index].

PMID- 29213007
TI  - The Value of Lesion Size as an Adjunct to the BI-RADS-MRI 2013 Descriptors in the
      Diagnosis of Solitary Breast Masses.
AB  - PURPOSE: This study aimed to evaluate the MRI findings of breast solitary masses
      in diagnostic procedures to decide the appropriate category based on American
      College of Radiology (ACR) BI-RADS-MRI 2013, with the focus on lesion size.
      METHODS: A retrospective review of 2,603 consecutive breast MRI reports
      identified 250 pathologically-proven solitary breast masses. Dynamic-contrast
      enhanced images and diffusion-weighted images were performed on a 3.0/1.5 Tesla
      Scanner with a 16/4 channel dedicated breast coil. MRI findings were re-evaluated
      according to ACR BI-RADS-MRI 2013. BI-RADS-MRI descriptors, lesion size and
      minimum apparent diffusion coefficient (ADC) value were statistically analyzed
      using univariate/multivariate logistic regression analysis and receiver operator
      characteristic (ROC) analysis. Based on the results, a diagnostic decision tree
      was constructed. RESULTS: Of the 250 lesions, 152 (61%) were malignant and 98
      (39%) were benign. In univariate logistic regression analysis, most of the BI
      RADS descriptors, lesion size, and ADC value were significant. Lesion size and
      ADC value were binarized with optimal cut-off values of 12 mm and 1.1 * 10-3
      mm2/s, respectively. Multivariate logistic regression analysis showed that lesion
      size (>=12 mm or not), margin (circumscribed or not), kinetics (washout or not)
      and internal enhancement characteristics (IEC) (rim enhancement present or
      absent) significantly contributed to the diagnosis (P < 0.05). Using these four
      significant parameters, a decision tree was constructed to categorize lesions
      into detailed assessment categories/subcategories (Category 4A, 4B, 4C and 5).
      CONCLUSION: Lesion size is an independent contributor in diagnosing solitary
      breast masses. Adding the information of lesion size to BI-RADS-MRI 2013
      descriptors will allow more detailed categorizations.

PMID- 29213008
TI  - The Relationship between Neurite Density Measured with Confocal Microscopy in a
      Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion
      Kurtosis Imaging.
AB  - PURPOSE: Diffusional kurtosis imaging (DKI) enables sensitive measurement of
      tissue microstructure by quantifying the non-Gaussian diffusion of water.
      Although DKI is widely applied in many situations, histological correlation with
      DKI analysis is lacking. The purpose of this study was to determine the
      relationship between DKI metrics and neurite density measured using confocal
      microscopy of a cleared mouse brain. METHODS: One thy-1 yellow fluorescent
      protein 16 mouse was deeply anesthetized and perfusion fixation was performed.
      The brain was carefully dissected out and whole-brain MRI was performed using a
      7T animal MRI system. DKI and diffusion tensor imaging (DTI) data were obtained.
      After the MRI scan, brain sections were prepared and then cleared using
      aminoalcohols (CUBIC). Confocal microscopy was performed using a two-photon
      confocal microscope with a laser. Forty-eight ROIs were set on the caudate
      putamen, seven ROIs on the anterior commissure, and seven ROIs on the ventral
      hippocampal commissure on the confocal microscopic image and a corresponding MR
      image. In each ROI, histological neurite density and the metrics of DKI and DTI
      were calculated. The correlations between diffusion metrics and neurite density
      were analyzed using Pearson correlation coefficient analysis. RESULTS: Mean
      kurtosis (MK) (P = 5.2 * 10-9, r = 0.73) and radial kurtosis (P = 2.3 * 10-9, r =
      0.74) strongly correlated with neurite density in the caudate putamen. The
      correlation between fractional anisotropy (FA) and neurite density was moderate
      (P = 0.0030, r = 0.42). In the anterior commissure and the ventral hippocampal
      commissure, neurite density and FA are very strongly correlated (P = 1.3 * 10-5,
      r = 0.90). MK in these areas were very high value and showed no significant
      correlation (P = 0.48). CONCLUSION: DKI accurately reflected neurite density in
      the area with crossing fibers, potentially allowing evaluation of complex
      microstructures.

PMID- 29213009
TI  - Concentration determination of urinary metabolites of N,N-dimethylacetamide by
      high-performance liquid chromatography-tandem mass spectrometry.
AB  - OBJECTIVES: N,N-Dimethylacetamide (DMAC) is widely used in industry as a solvent.
      It can be absorbed through human skin. Therefore, it is necessary to determine
      exposure to DMAC via biological monitoring. However, the precision of traditional
      gas chromatography (GC) is low due to the thermal decomposition of metabolites in
      the high-temperature GC injection port. To overcome this problem, we have
      developed a new method for the simultaneous separation and quantification of
      urinary DMAC metabolites using liquid chromatography-tandem mass spectrometry (LC
      MS/MS). METHODS: Urine samples were diluted 10-fold in formic acid, and 1-MUl
      aliquots were injected into the LC-MS/MS equipment. A C18 reverse-phase Octa
      Decyl Silyl (ODS) column was used as the analytical column, and the mobile phase
      consisted of a mixture of methanol and aqueous formic acid solution. RESULTS:
      Urinary concentrations of DMAC and its known metabolites (N-hydroxymethyl-N
      methylacetamide (DMAC-OH), N-methylacetamide (NMAC), and S- (acetamidomethyl)
      mercapturic acid (AMMA) ) were determined in a single run. The dynamic ranges of
      the calibration curves were 0.05-5 mg/l (r>=0.999) for all four compounds. The
      limits of detection for DMAC, DMAC-OH, NMAC, and AMMA in urine were 0.04, 0.02,
      0.05, and 0.02 mg/l, respectively. Within-run accuracies were 96.5%-109.6% with
      relative standard deviations of precision being 3.43%-10.31%. CONCLUSIONS: The
      results demonstrated that the proposed method could successfully quantify low
      concentrations of DMAC and its metabolites with high precision. Hence, this
      method is useful for evaluating DMAC exposure. In addition, this method can be
      used to examine metabolite behaviors in human bodies after exposure and to select
      appropriate biomarkers.

PMID- 29213010
TI  - Continuous improvement of fitness-for-duty management programs for workers
      engaging in stabilizing and decommissioning work at the Fukushima Daiichi Nuclear
      Power Plant.
AB  - BACKGROUND: Numerous workers have participated in recovery efforts following the
      accident that occurred at the Tokyo Electric Power Company (TEPCO) Fukushima
      Daiichi Nuclear Power Plant after the Great East Japan Earthquake. These workers,
      belonging to various companies, have been engaged in various tasks since the
      accident. Given the hazards and stress involved in these tasks and the relatively
      long time required to transport sick or injured workers to medical institutions,
      it became necessary to quickly implement a more stringent management program for
      fitness for duty than in ordinary work environments. CASE: It took considerable
      time to introduce and improve a fitness-for-duty program because of several
      concerns. Various efforts were conducted, sometimes triggered by guidance from
      the Ministry of Health, Labour and Welfare (MHLW), but the implementation of the
      program was insufficient. In April 2016, a new program was initiated in which all
      primary contractors confirmed that their subcontractors had achieved five
      conditions for workers' fitness for duty on the basis of guidance from the MHLW
      and occupational health experts. TEPCO confirmed that all primary contractors had
      implemented the program successfully as of the end of November 2016. CONCLUSION:
      Following a disaster, even though the parties concerned understand the necessity
      of fitness-for-duty programs and that companies in high positions have
      responsibilities beyond their legal requirements, it is highly possible that they
      may hesitate to introduce such programs without guidance from the government. It
      is necessary to prepare a governmental framework and professional resources that
      introduce these stringent management programs quickly.

PMID- 29213011
TI  - The prevalence of occupational health-related problems in dentistry: A review of
      the literature.
AB  - : The study was conducted to report on the scope and prevalence of occupational
      health related-problems experienced by dentists, dental therapists, and oral
      hygienists in their practice of dentistry. BACKGROUND: Professional practice and
      dental training have many risk factors, and the dental team should be able to
      recognize these factors to protect themselves. The prevalence of conditions
      related to the musculoskeletal system, stress, percutaneous injuries, ears, and
      eyes are of concern. The dental team should also not forget hepatitis B,
      hepatitis C, and HIV as risks in practice. Dental practitioners should protect
      themselves by self-recognizing risk factors and by maintaining proper working
      conditions. METHODS: The study targeted all empirical research, case studies, and
      systematic literature reviews written in English. All articles selected were
      subjected to a data analysis process. Data were captured on an Excel spreadsheet
      and reported in a comprehensive table. RESULTS: The literature addressing
      occupational health among dental practitioners included mainly cross-sectional
      studies and review papers (2001-2016). Forty-nine studies were included in the
      review. Musculoskeletal disorders remain the most researched occupational health
      related problems in dentistry. Eye protection compliance was low among
      practitioners. Percutaneous injuries especially among young dentists and students
      were still a concern. CONCLUSION: Occupational health-related problems are still
      prevalent in current dentistry practice, despite changes in equipment and surgery
      design. The reported prevalence of occupational related-health problems and other
      findings of investigative studies highlight the need for continuous professional
      education and a need to improve clinical practice aspects of dentistry curricula.

PMID- 29213012
TI  - Guidelines for personal exposure monitoring of chemicals: Part III.
AB  - This Document, "Guidelines for personal exposure monitoring of chemicals" ("this
      Guideline"), has been prepared by "The Committee for Personal Exposure
      Monitoring" ("the Committee") of the Expert Division of Occupational Hygiene &
      Ergonomics, Japan Society for Occupational Health. Considering the background of
      the growing importance of personal exposure monitoring in risk assessment and the
      need to prepare for the introduction of monitoring using personal samplers from
      an administrative perspective in recent years, the Committee was organized in
      November 2012. The Committee has prepared this Guideline as a "practical
      guideline" for personal exposure monitoring, so as to offer proposals and
      recommendations to the members of the Japan Society for Occupational Health and
      to society in general. The scope of this Guideline covers all chemical substances
      and all related workplaces regarded as targets for general assessment and the
      management of risk. It thus is not to be considered to comment on legal
      regulations and methodology. The main text provides the basic methods and
      concepts of personal exposure monitoring, while 31 "Appendices" are provided in
      this Guideline throughout the series; technical descriptions, statistical bases,
      and actual workplace examples are provided in these appendices, to assist better
      understanding. The personal exposure monitoring described as per this Guideline
      is equivalent to an "expert-centered basic method to reasonably proceed with the
      assessment and management of risk at workplaces." It is considered that
      practicing and expanding on this method will significantly contribute in
      reforming the overall framework of occupational hygiene management in Japan.

PMID- 29213013
TI  - Annexin A1 is a novel target gene of gonadotropin-releasing hormone in LbetaT2
      gonadotrope cells.
AB  - Gonadotropin-releasing hormone (GnRH) regulates gonadotropin secretion. We
      previously demonstrated that the expression of annexin A5 (ANXA5) is stimulated
      by GnRH in gonadotropes and has a significant role in gonadotropin secretion. It
      is therefore of interest to know whether other members of the ANXA family, which
      consists of twelve structurally related members, are also regulated by GnRH.
      Therefore, the expression of all annexins was examined in LbetaT2 gonadotrope
      cells. ANXA4, A5, A6, A7 and A11 were detected in LbetaT2 cells. The expression
      of ANXA5 and A1 mRNA was stimulated by a GnRH agonist. An increase in ANXA1
      protein by this agonist was demonstrated by western blotting.
      Immunohistochemistry showed that ANXA1 was present in the nucleus and to a lesser
      extent in the cytoplasm of some rat pituitary cells. The GnRH agonist induced
      translocation of ANXA1 to the periphery of LbetaT2 cells. The presence of ANXA1
      in gonadotropes and its increase upon GnRH agonist treatment were confirmed in a
      primary pituitary cell culture. ANXA1 expression was also demonstrated in the
      ovary, the testis, the thyroid gland and the pancreas in a different manner to
      that of ANXA5. These data suggest that ANXA1 is a novel GnRH target gene in
      gonadotropes. ANXA1 also may be a target of local GnRH in peripheral tissues and
      may have a different role than that of ANXA5.

PMID- 29213014
TI  - A case of a giant mass in the lumbar region of a newborn calf.
AB  - The present report describes a newborn calf with spina bifida that presented with
      a giant mass of the lumbar region, as well as subsequent gross, histological, and
      immunohistochemical examinations. A malformed Japanese black calf (estimated
      weight = 20 kg) was euthanized immediately after birth. A gross evaluation
      revealed a giant mass (approximately 60 cm * 30 cm * 15 cm) covered by the hair
      coat in the lumbar region and connected with the hair coat of the trunk. The mass
      surface was divided by a deep polygonal groove and externally resembled a
      lobulated kidney. Histology and immunohistochemistry revealed that the giant mass
      comprised a vessel, bronchiolus lined with cuboidal epithelium, and small
      alveolus. Bone bleaching revealed various abnormalities, including spina bifida,
      vertebral fusion, vertebral deformity, vertebral malformation, vertebral
      scoliosis, and coxal bone malformation. Following a suggestion that the giant
      lumbar region mass was occupied by lung tissue, this case was considered to
      involve an asymmetric conjoined duplicitas that resulted in a very rare
      dichotomous spondylosis malformation.

PMID- 29213015
TI  - Midline sensory nerve supply to the anoscrotal junction: a study using human male
      fetuses.
AB  - The origin of the posterior scrotal nerve is considered to be the bilateral
      pudendal nerves but the course to the midline is still obscure. Using 5 late
      stage human male fetuses, we identified the single nerve through the
      intramuscular midline septum of the bulbospongiosus and the bilateral nerves
      along the left and right sides of the septum. Thus, the posterior scrotal nerve
      showed a variation: a single midline trunk or bilateral nerves. Branches of the
      bilateral pudendal nerves ran medially between the muscle and Cowper's gland and,
      at the midline area, they joined or associated closely. During the proximal
      course, much or less, the nerve penetrated the superior part of the muscle. The
      nerve entered the subcutaneous tissue at and near the perineal raphe. The
      communication with intrapelvic autonomic nerves were suggested behind Cowper's
      gland. Notably, the midline skin immediately anterior to the anus carried a
      considerable dense supply of thin sensory nerves. However, these nerves seemed to
      come from a space between the rectal smooth muscle and the external anal
      sphincter, not from the posterior scrotal nerve. Therefore, surgical treatment of
      the intersphincteric layer was likely to injure the original sensory nerve supply
      to the anterior anal skin.

PMID- 29213016
TI  - Changes in topographical relation between the ductus arteriosus and left
      subclavian artery in human embryos: a study using serial sections.
AB  - At birth, the ductus arteriosus (DA) merges with the aortic arch in the caudal
      side of the origin of the left subclavian artery (ltSCA). Since the SCA (seventh
      segmental arteries) were fixed on the levels of the seventh cervical-first
      thoracic vertebral bodies, the confluence of the DA should migrate caudally
      toward the lower level. We aimed to describe the changing topographical anatomy
      of the DA and SCA using serial sections. First, we examined serial sagittal
      sections of 11 embryos (Carnegie stage 15-18), but the specimens were clearly
      divided into 2 groups with and without the lower confluence of the DA. Next, we
      examined serial horizontal sections of 40 specimens (Carnegie stage 14-16) and we
      chose 5 specimens (CRL 11 mm, 3 specimen; 1, 14 mm; 1, 15 mm) including the DA
      near (within 1-vertebral segment from) the ltSCA. The final approach of the DA
      occurred during the heart descent in which the apex of the heart migrated from
      the level of the first to the fourth thoracic vertebral body. Thus, the DA
      reached the SCA level before establishment of the heart descent. The right aortic
      arch maintained its entire course in 2 of the 5 specimens. Therefore, the
      positioning of the DA along the left aortic arch might occur independently of
      degeneration of the right arch. Notably, the tracheal bifurcation level was
      higher when the DA-ltSCA distance was greater. A contribution of the increased
      pulmonary volume was suggested for the final approach of the DA.

PMID- 29213017
TI  - Topographical anatomy of the pronator teres muscle and median nerve: a study
      using histological sections of human fetuses.
AB  - The median nerve passes through the humeral and ulnar heads of the pronator teres
      muscle (PT), although variations such as absence of the ulnar head may exist. We
      observed histological sections of the upper extremity from 24 embryos and
      fetuses. In the early stage, the PT extended between the radius and the medial
      epicondyle of the humerus, but no candidate for the ulnar head was found. In mid
      term fetuses, the ulnar margin of the PT was attached to the elbow joint capsule.
      Moreover, in late-stage fetuses, a small deep part of the PT arose from the thick
      joint capsule of the humero-ulnar joint near the coronoid process of the ulna.
      This joint capsule also provided the most proximal origin of the flexor digitorum
      profundus muscle. Therefore, we considered fetal PT origin from the capsule as a
      likely candidate for the ulnar head. Consequently, the PT seemed to develop from
      a single anlage through which the median nerve passed, but later - possibly after
      birth - a small PT origin from the joint capsule appeared to obtain an
      aponeurosis connecting the muscle fiber to the ulna. This secondary change in PT
      morphology might explain the muscle variation seen in adults.

PMID- 29213018
TI  - Morphological changes indicative of brain hemisphere development and handedness
      in fixed brains and on CT/MRI images.
AB  - We measured the lengths of some parts of the right and left hemispheres (HEs) in
      70 formalin-fixed brains and on 15 computed tomography/magnetic resonance imaging
      (CT/MRI) images (7 left-handed and 8 right-handed cases) to clarify the
      morphological changes indicating which HE developed earlier and handedness. In
      many cases of the fixed brains, 1) the distance from the frontal pole to the
      occipital pole was longer in the left HE than in the right HE, 2) the distance
      from the middle plane to the lateral-most portion of the HE was wider in the
      right HE than in the left HE, 3) the left occipital pole elongated more
      posteriorly and covered the right occipital pole, and 4) the volume of each HE
      was nearly the same. The results indicate that the left HE develops and grows
      slightly earlier in the larger semi-cranium (half of the cranium) than the right
      HE which develops later in the smaller semi-cranium. The whole brain was more
      spherical in the female cases than in the male cases. The morphological changes
      in both HEs for handedness were not evident on the CT/MRI images.

PMID- 29213019
TI  - [Early chronic pancreatitis:current issues and perspective].

PMID- 29213020
TI  - [Diagnosis for chronic pancreatitis].

PMID- 29213021
TI  - [New developments in non-surgical treatment of chronic pancreatitis].

PMID- 29213022
TI  - [Surgical management of chronic pancreatitis].

PMID- 29213023
TI  - [Tracheobronchitis as an extraintestinal manifestation of Crohn's disease].
AB  - A 27-year-old woman with Crohn's disease, who had sustained clinical remission
      for two years following treatment with mesalazine and nutrition therapy, was
      admitted to our hospital complaining of dry cough, mild dysphagia, and slight
      fever. A computed tomography of the chest demonstrated an increase in the
      thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and
      edematous mucosa with whitish granular lesions in the trachea and main carina.
      Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed
      tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was
      treated with 40mg/day prednisolone. Her symptoms improved immediately. However,
      dry cough recurred two months after prednisolone treatment, and further treatment
      with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's
      disease is rare, with only 13 cases having been reported. Tracheal involvement
      should be considered in Crohn's disease patients with respiratory symptoms.

PMID- 29213024
TI  - [A refractory case of ulcerative colitis developed after the cessation smoking
      achieved clinical and endoscopic remission after resuming smoking].
AB  - A 42-year-old man, who had stopped smoking almost one year ago, visited our
      hospital for hematochezia. He was diagnosed as having ulcerative colitis and was
      prescribed 5-amino salicylic acid and corticosteroids, which led to the remission
      of his disease. However, the disease relapsed after sufficient continuous
      corticosteroids administration and persisted despite 5-amino salicylic acid
      administration and intensive treatment with corticosteroids, immune modulators,
      leukocyte apheresis, and anti-TNF-alpha antibodies. Curiously, clinical remission
      was achieved after he resumed smoking, and colonoscopy revealed mucosal healing.
      Such remission may be attributable to anti-inflammatory effects of smoking
      nicotine and carbon oxides.

PMID- 29213025
TI  - [A case of non-invasive IPMC with fibrotic lesion-like "tubular complex"].
AB  - A 73-year-old man was incidentally diagnosed with a cystic lesion in the
      pancreatic body. Ultrasonography, abdominal computed tomography, magnetic
      resonance imaging, endoscopic retrograde cholangiopancreatography, and endoscopic
      ultrasound were performed, and a nodule was detected in the cystic lesion along
      with an irregularity of the main pancreatic duct. An initial diagnosis of a mixed
      type intraductal papillary mucinous neoplasm was made, and a central
      pancreatectomy was performed. However, the final diagnosis was altered to non
      invasive intraductal papillary mucinous carcinoma (IPMC). The histopathological
      examination revealed a fibrotic lesion that was similar to "tubular complex"
      findings observed in mouse models of pancreatic cancer. The fibrotic lesion was
      placed between the main pancreatic duct lesion and branch-duct cystic lesion. The
      changes reflected in branch-level stenosis may be caused by IPMC growth.

PMID- 29213026
TI  - [Case of protein plug in the pancreatic duct mimicking pancreatic cancer
      concomitant with branch-type intraductal papillary mucinous neoplasm].
AB  - A 65-year-old male was referred to our hospital 2 years ago for a multilocular
      cyst accompanied with a protein plug in the pancreas tail. He was diagnosed as
      having branch duct-type intraductal papillary mucinous neoplasm and was followed
      up. Two years later, endoscopic ultrasonography revealed a hypoechoic lesion,
      10mm in diameter, near the cyst-like lesion. Finally, he was diagnosed with small
      pancreatic adenocarcinoma concomitant with intraductal papillary mucinous
      neoplasm and underwent radical distal pancreatectomy with splenectomy. Resected
      specimen revealed that the protein plug in the main pancreatic duct had caused
      distal pancreatic duct dilatation, resembling a multilocular cyst and pancreatic
      duct stenosis with inflammatory changes and fibrosis around the pancreatic
      parenchyma. Here, we report a rare case of protein plugs in the pancreatic duct
      mimicking pancreatic cancer concomitant with branch-type intraductal papillary
      mucinous neoplasm.

PMID- 29213027
TI  - [Autoimmune pancreatitis and IgG4-related hepatic inflammatory pseudotumor
      complicated by an impacted pancreatic stone at the major papilla during steroid
      treatment].
AB  - A 79-year-old male presented to our hospital with abdominal discomfort and was
      diagnosed with mass-forming pancreatitis. During follow-up, pancreatic stones and
      a hepatic mass with peripheral bile duct dilation were discovered. Serum IgG4
      level was elevated, and a liver tumor biopsy revealed numerous IgG4-positive
      plasma cells and fibrosis. Chronic pancreatitis with the suspected involvement of
      autoimmune pancreatitis (AIP) and IgG4-related hepatic inflammatory pseudotumor
      (IgG4-HIP) was diagnosed. Therefore, a steroid treatment was initiated. However,
      2 months later, the patient complained of epigastric pain that was found to be
      caused by an impacted pancreatic stone in the major papilla, which was
      endoscopically removed. Follow-up imaging findings confirmed the improvement in
      AIP and the dissolution of the IgG4-HIP.

PMID- 29213028
TI  - [Acute cholecystitis due to microscopic polyangiitis:a case report].
AB  - A 78-year-old man with chief complaints of cough and lower limb numbness was
      admitted to our hospital. Serum myeloperoxidase-antineutrophil cytoplasmic
      antibody titer (MPO-ANCA) was elevated (48.8U/ml), and a diagnosis of microscopic
      polyangiitis (MPA) was made. After admission, the patient developed a fever and
      right upper quadrant pain. Ultrasonography and computed tomography revealed an
      acute cholecystitis of unknown cause, and laparoscopic cholecystectomy was
      performed. Histopathological examination of the resected gallbladder revealed
      necrotizing vasculitis along with the infiltration of eosinophils, lymphocytes,
      and plasma cells around the small arteries in the muscular layer of the
      gallbladder, which are characteristics of MPA.

PMID- 29213029
TI  - Generation of Methicillin-Resistant Staphylococcus Aureus Biofilm Infection in an
      Immunosuppressed Rat Model.
AB  - BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a common
      pathogen responsible for many related infections, and immunosuppressed
      individuals are more susceptible. Its pathogenicity is associated with its
      virulence factors, resistance to antibiotics, and ability to form biofilm (BF).
      MRSA-BF infections in immunosuppressed patients pose great difficulties to
      clinical treatment. MATERIAL AND METHODS The study aimed to establish a model of
      MRSA-BF infection in rats with cyclophosphamide (CTX)-induced immunosuppression.
      For this, rats were administered CTX on days 1 and 4. White blood cells (WBC)
      were counted, then rats were inoculated with a clinical MRSA 17546 (t037) on day
      5. Rats were sacrificed on days 6-10 and tissue samples were examined by scanning
      electron microscopy. RESULTS Using the dose of CTX: 150 (mg/kg) + 100 (mg/kg) is
      better than the other 2 programs as the survival rates of the immunocompromised
      rats were higher than in the other 2 immunosuppressive groups. The survival rate
      was not different between rats in the clean environment and in the SPF
      environment. However, the survival rate was affected by the sample acquisitions.
      Importantly, WBC counts started to decline on day 4, and then started to rise on
      day 9. Moreover, MRSA-BFs were formed earlier in immunosuppressed rats compared
      to the normal rats, as shown by scanning electron microscopy. CONCLUSIONS The
      study successfully established an immunosuppressed rat model of MRSA-BF
      infection, which provides methodological and data support for establishment of
      such animal models and is useful reference for related research. Our results may
      help further investigation of MRSA-BF infection.

PMID- 29213030
TI  - Acute Bilateral Ophthalmoplegia Due to Vertebrobasilar Dolichoectasia: A Report
      of Two Cases.
AB  - BACKGROUND Vertebrobasilar dolichoectasia (VBD) is a complex progressive arterial
      disease characterized by dilation, elongation, and tortuosity of the vertebral
      and basilar arteries, and may be congenital or acquired. VBD may lead to
      progressive compression of the brainstem, cranial nerve abnormalities, and
      intracranial hemorrhage, but may also be associated with arterial thrombosis,
      with ischemic stroke as the most common clinical outcome. CASE REPORT Two cases
      of VBD are presented, both with acute bilateral ophthalmoplegia and cranial nerve
      palsies, and vertebrobasilar arterial thrombosis that resulted in ischemic
      stroke. CONCLUSIONS VBD is a complex arterial disease with a variety of clinical
      manifestation, with bilateral ophthalmoplegia being a rare presentation. Clinical
      management of VBD is a challenge as there are no current management guidelines.
      Therefore, clinical management of cases of VBD should be individualized to
      balance the risks and benefits of treatment options for each patient.

PMID- 29213031
TI  - [Neuronet restructuring in focal and generalized epilepsy according to resting
      state fMRI].
AB  - AIM: To compare neuronet restructuring in focal and generalized epilepsy.
      MATERIAL AND METHODS: Seventy-seven patients, aged from 18 to 65 years, with the
      diagnosis of epilepsy, including 63 patients with focal epilepsy and 14 with
      generalized epilepsy, were examined. A control group included 23 healthy people.
      Neuronet restructuring was studied using fMRI. RESULTS AND CONCLUSION: According
      to resting state fMRI, there were between-group differences in spatial
      organization (activity map) of the brain structures as well as in the results of
      cross-correlation analysis of interaction maps of resting-state networks. It has
      been concluded that functional restructuring in connectomes in focal and
      generalized epilepsy have the opposite patterns of disorganization (toward
      increase or decrease) in most structures studied though there are structures with
      the same direction of connectivity changes.

PMID- 29213032
TI  - [Staging of neuroplasticity alterations during epileptogenesis (temporal lobe
      epileply as an example)].
AB  - Using temporal lobe epilepsy as an example, staging of long term plasticity in
      the hippocampus is considered. Major stages demonstrating opposite alterations in
      neuroplasticity are active epileptogenesis and the period of established temporal
      lobe epilepsy. During the epileptogenesis, multiple events resulting in forming
      of epileptic neuronal nets occur: changes in glutamatergic and GABAergic neurons,
      increase of aberrant neurogenesis, axonal sprouting and dendrite remodeling,
      particularly, supported by an excessive enhancement of the BDNF system in
      specific hippocampal regions. As epileptogenesis progresses, this stage of an
      aberrant superplasticity is changing for opposite events accompanying formation
      of the epileptogenic focus and limiting plasticity: axonal damage, neuronal cell
      death, hippocampal sclerosis, suppression of neurogenesis. At this
      neurodegenerative stage of temporal epilepsy, the inclusion of neuroprotectants
      with neurotrophic properties (e.g. drugs containing cerebral peptide
      hydrolizates) into the treatment protocol appears promising. Potential use of
      such neuroprotectants during the active epileptogenesis period is discussed.

PMID- 29213033
TI  - [Epigenetic modifications of chromatin in epilepsy: a potential mechanism of
      pharmacoresistance?]
AB  - Pharmacoresistance in epilepsy is an important problem from both clinical and
      fundamental perspectives. The existent hypotheses of pharmacoresistance are based
      on long term plastic rebuilding of the epileptic brain. One of potential
      mechanisms mediating such protracted changes are alterations of gene expression
      induced by epigenetic modifications of chromatin in brain cells of epileptic
      patients. Recently, changes in DNA methylation and histone post-translational
      modifications were reported in brain tissues of patients with pharmacoresistant
      epilepsy. Unfortunately, these data remain fragmentary and contradictory,
      therefore the results of animal models can partially fill this gap. The authors
      present a short review of the data concerning a potential role of epigenetic
      modifications in epilepsy.

PMID- 29213034
TI  - [Classification of epileptic seizures and epilepsy (2017)].

PMID- 29213035
TI  - [Problems of juvenile myoclonic epilepsy. A view through the prism of time].
AB  - The authors present a comparative analysis of the results of the study of 72
      adolescent patients with juvenile myoclonic epilepsy (JME), which were published
      in 2010, and a new sample of patients over the last 5 years with the publications
      of domestic and foreign authors. Difficult clinical cases are described. These
      data indicate positive shifts in the diagnosis and treatment of JME. However, the
      question of diagnosis is still a hard problem for neurologists. The questions to
      be resolved are: gender aspect of the disease, to what extent levetiracetam could
      be a drug of first choice and to what extent valproats could be replaced;
      monitoring of children born to mothers with JME, a role of paternal inheritance.

PMID- 29213036
TI  - [Pathomorphosis of idiopathic generalized epilepsy. Juvenile forms].
AB  - AIM: To investigate the pathomorphosis of idiopathic generalized epilepsy (IGE)
      in the aspect of prognosis. MATERIAL AND METHODS: The study involved 1480
      patients with epilepsy including 281 patients with IGE. RESULTS AND CONCLUSION:
      'Juvenile' forms were diagnosed in 228 patients. Relapse of seizures in anamnesis
      occurred in 19% out of 105 patients with juvenile myoclonic epilepsy (JME).
      Remission was achieved in 59.2% out of 76 patients with long-term follow-up. Out
      of 35 patients with juvenile absence epilepsy (JAE), relapse of seizures in
      anamnesis occurred in 25.7%. Out of 24 patients with long-term follow-up,
      remission was achieved in 70.8%. Out of 88 patients with IGE with generalized
      tonic clonic-seizures, relapse of seizures in anamnesis occurred in 15%. Out of
      60 patients with long-term follow-up, remission was achieved in 86.7%. The main
      features of epilepsy pathomorphosis in all groups of patients were the decrease
      of informativeness of routine EEG, reduction in the frequency and duration of
      seizures, occurrence of seizures in the discontinuation of therapy and/or under
      the influence of provoking factors.

PMID- 29213037
TI  - [Interictal dysphoric disorder: a current state of the problem].
AB  - The authors present a clinical description of interictal dysphoric disorder in
      patients with epilepsy compared to other similar disorders. The comorbidities of
      epilepsy and affective disorders, including atypical forms, are reviewed.
      Clinical aspects of affective somatoform syndrome are discussed.

PMID- 29213038
TI  - [An influence of interictal anxiety on coping and self-control strategies for
      epileptic seizures in patients with temporal lobe epilepsy].
AB  - AIM: A comparative analysis of coping and self-control strategies for epileptic
      seizures in temporal lobe epilepsy patients with and without interictal anxiety.
      MATERIAL AND METHODS: Authors evaluated interictal anxiety (IA) with HADS,
      strategies for seizure control with CBES-SC, coping-style with BriefCOPE scale
      and quality of life with QOLIE-31-P scale in 45 patients with temporal lobe
      epilepsy (TLE). The control group consisted of 86 healthy individuals. RESULTS:
      In 35% of patients with TLE, the anxiety (HADS) was higher compared to the normal
      level. TLE patients with IA had a lower quality of life compared to patients
      without IA (51.19+/-12.39% vs. 65.43+/-18.11%, p=0.008). A comparative analysis
      of coping strategies in TLE patients with and without IA showed that patients
      with IA used such strategies as 'venting' and 'behavioral disengagement' more
      often. Patients with IA had a higher emotional coping style score (r<0.05) and
      used strategies for seizure control more often (71% of patients with IA vs. 32%
      of patients without IA, chi2=6.282, r<0.05), but there were no significant
      differences in the effectiveness of seizure control between groups. CONCLUSION:
      Associative interactions between interictal anxiety, emotional coping style and
      low quality of life were shown. This gives grounds for regarding anxiety as a
      target for treatment. At the same time, anxiety motivates patients to a wider use
      of self-management strategies, but has no impact on the effectiveness of seizure
      control.

PMID- 29213039
TI  - [Cognitive impairment. The effects of seizures?]
AB  - This review discusses articles on cognitive impairments developing after one or
      more convulsive seizures. Cognitive disorders seem to be frequent complications
      of epilepsy. According to recent clinical studies, the intensity of cognitive
      declines depends on a frequency and severity of seizures. However, presence of an
      epileptic focus does not always indicate an increase in cognitive impairments. An
      effect of a single convulsive seizure on cognitive functions at this stage is
      uncertain. According to some data, cognitive impairments after a single
      generalized seizures develop only in specific clinical syndromes, on the other
      hand, they are influenced by the emotional state of the subject. This problem
      remains relevant today. Further work is needed in this direction.

PMID- 29213040
TI  - [Brivaracetam in the treatment of patients with epilepsy].
AB  - The newest antiepileptic drug (AED) brivaracetam (Briviac, UCB Pharma) (BRV) was
      approved in the Russian Federation in 2017 as an adjuvant therapy for the
      treatment of partial seizures with/without secondary generalization in adults and
      adolescents over 16 years old with epilepsy. This review contains the data of BRV
      preclinical studies, pharmacokinetic profile and the results of comparative study
      of BRV and LEV. The results of main studies of efficacy and tolerability with
      pooled analysis as well as data from meta-analysis are presented. The authors
      present conclusions of the Russian leading epileptologists on perspectives of
      using BRV in different populations of epileptic patients. The use of BRV is able
      to provide long-term efficacy in terms of seizure control, is well tolerated,
      keeps quality of life and social activity of people with epilepsy.

PMID- 29213041
TI  - [Perampanel in the treatment of patients with epilepsy].
AB  - Development of new antiepileptic drugs (AED) does not stop due to the fact that
      the number of patients with pharmacoresistant epilepsy remains at about 30%. One
      of the newest AEDs is perampanel (PER), a selective, non-competitive AMPA
      receptor antagonist to target post-synaptic glutamate transmission. PER is
      approved in the Russian Federation as adjunctive treatment for focal seizures
      with or without secondarily generalized seizures and for primary generalized
      tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE) in patients
      with epilepsy aged >=12 years. The drug is effective and well-tolerated in the
      dose of 4-8 mg/day, and most side effects are dose-dependent. The high efficacy
      of PER combined with the good tolerability, absence of life-threatening adverse
      reactions and convenient intake allow us to recommend PER as the first choice
      additional drug in treatment of patients with epilepsy.

PMID- 29213042
TI  - [New opportunities in the optimization of epilepsy treatment in adolescents].
AB  - In the pubertal period, the most severe forms of childhood epilepsy persist and
      are modified; genetically determined syndromes, atypical for early and late age
      periods, make their debut. Hereditary predisposition, instability of homeostatic
      mechanisms, neuroendocrine restructuring at the age of puberty and the influence
      of factors contributing to the realization of a genetic defect lead to a long
      term transformation of mediator systems and formation of epileptic activity in
      adolescents. The authors present common approaches in the treatment and
      characterization of the modern antiepileptic drug perampanel, which is highly
      effective in treatment of patients with resistant forms of epilepsy. The article
      presents a summarized overview of the clinical forms of adolescent epilepsy
      observed in a psychoneurological department and an analysis of treatment results.
      A clinical case of the successful use of the antiepileptic drug perampanel in a
      female patient with focal seizures with secondary generalization of epilepsy,
      type I neurofibromatosis is presented.

PMID- 29213043
TI  - [Subcortical laminar heterotopia 'double cortex syndrome'].
AB  - This article presents a clinical case of a 29-year-old patient with 'Double
      cortex syndrome' with epilepsy, intellectual and mental disorders. Subcortical
      band heterotopia is a rare disorder of neuronal migration. Such patients
      typically present with epilepsy and variable degrees of mental retardation and
      behavioral and intellectual disturbances. The main diagnostic method is magnetic
      resonance imaging (MRI).

PMID- 29213044
TI  - [The course and development of epilepsy in patients with typical variant of Rett
      syndrome and mutations].
AB  - AIM: To study the anamnesis, clinical state, electro-encephalographic and brain
      MRI characteristics in patients with Rett syndrome (MESR2) and epilepsy. MATERIAL
      AND METHODS: Eleven female patients, aged from 3 to 23 years, with Rett syndrome
      and MeCP2 mutations were studied. The study continued for 10 years (2006-2015).
      Assessment of neurological and mental status, night sleep video-EEG monitoring,
      MRI were performed. RESULTS AND CONCLUSION: Epilepsy was diagnosed in six cases
      (54.5%). Mean age at onset of epileptic seizures was 3 years 9 month. The
      following types of seizures were described: generalized, myoclonic, myotonic,
      tonic, versive, focal motor, atypical absences. Status epilepticus developed in
      one patient. Generalized seizures were identified in 56.25%, focal seizures in
      43.75%. EEG changes were found in 9 patients (81.8%): slowing of the activity,
      episodes of periodic regional slowing, regional epileptiform activity and diffuse
      epileptiform activity, benign focal epileptiform discharges (BFED) of childhood,
      multiregional epileptiform activity. Five patients were treated with
      antiepileptic drugs. All of them had improved during treatment: a reduction of
      frequency of seizures was up to 50% in 4 cases (80%). One patient with resistant
      epilepsy was treated with the combination of drugs (levetiracetam, topiramate,
      zonisamide, benzodiazepine) that led to stopping of seizures during night sleep
      and decrease in the frequency of daytime seizures by 50%. Further research of
      epilepsy and efficacy of antiepileptic drugs in Rett syndrome is required.

PMID- 29213045
TI  - [An effect of epilepsy on sleep structure].
AB  - In this review, the authors discuss the problem of management of the patient with
      epilepsy with regard an impact of epileptic seizures and syndromes on sleep
      structure. Sleep disorders can lead to worsening of seizure control and general
      medical condition of the patients. However, seizures themselves and types of
      epilepsy can affect the sleep architecture. One of the most frequent symptoms of
      disordered sleep in epilepsy patients is excessive daytime sleepiness, which can
      be a consequence of poor sleep quality due to frequent nocturnal seizures or
      excessive interictal epileptiform activity during sleep leading to frequent
      arousals. is frequently referred to antiepileptic drug side effects. In patients
      with frontal and temporal lobe epilepsies, which are more associated with sleep,
      the sleep architecture is significantly different from healthy individuals. They
      have more frequent arousals, disturbed relationship between sleep phases and
      stages, in particular inhibited REM-sleep phase. Most recent data on this problem
      are reviewed. Sleep patterns for different major epileptic syndromes are
      presented and some general recommendations for patient management, with a special
      consideration of sleep issues, are given.

PMID- 29213046
TI  - [Medical-social expertise in epilepsy].
AB  - AIM: Clinical and expert analysis of the data, determining the severity of
      permanent disabilities in patients with epilepsy, based on the new
      classifications and criteria used for the implementation of medical and social
      examination from 2016. MATERIAL AND METHODS: Two hundred acts of examination of
      patients with epilepsy in medical and social examination bureaus were analyzed
      using statistical, clinical expertise and graphic methods. RESULTS AND
      CONCLUSION: A clinical expert analysis showed that the assessment of the
      limitations of life in epilepsy patients and people with disabilities requires an
      integrated approach. Not only seizures (their severity and frequency), but also
      gradually growing changes of the cognitive sphere and personality disorders,
      should be taken into account when making expert decisions. A typology of the
      formation of individual rehabilitation programs is presented.

PMID- 29213048
TI  - In vivo evidence for homo- and heterodimeric interactions of Arabidopsis thaliana
      dehydrins AtCOR47, AtERD10, and AtRAB18.
AB  - Dehydrins (DHNs) are intrinsically disordered proteins that play central roles in
      plant abiotic stress responses; however, how they work remains unclear. Herein,
      we report the in planta subcellular localization of Arabidopsis thaliana DHNs
      AtCOR47, AtERD10, and AtRAB18 through GFP translational fusions. To explore the
      dimerization ability of the Arabidopsis acidic DHNs AtCOR47 and AtERD10, we
      conducted an in planta DHN binding assay using the Bimolecular Fluorescence
      Complementation (BiFC) technique. Our analyses revealed homodimeric interactions
      for AtCOR47 and AtERD10; interestingly, heterodimeric associations also occurred
      with these DHNs, and these interactions were observed in the cytosol of tobacco
      cells. Furthermore, we evaluated whether Arabidopsis basic DHNs, such as AtRAB18,
      could also interact with itself and/or with AtCOR47 and AtERD10 in the BiFC
      system. Our data revealed homodimeric RAB18 complexes in the nucleus and cytosol,
      while heterodimeric associations between AtRAB18 and acidic DHNs occurred only in
      the cytosol. Finally, we demonstrated the presence of heterodimeric complexes
      among Arabidopsis AtCOR47, AtERD10, and AtRAB18 DHNs with their acidic ortholog
      the OpsDHN1 from Opuntia streptacantha; these heterodimeric interactions showed
      different subcellular distributions. Our results guide DHN research toward a new
      scenario where DHN/DHN oligomerization could be explored as a part of their
      molecular mechanism.

PMID- 29213047
TI  - Differentially evolved glucosyltransferases determine natural variation of rice
      flavone accumulation and UV-tolerance.
AB  - Decoration of phytochemicals contributes to the majority of metabolic diversity
      in nature, whereas how this process alters the biological functions of their
      precursor molecules remains to be investigated. Flavones, an important yet
      overlooked subclass of flavonoids, are most commonly conjugated with sugar
      moieties by UDP-dependent glycosyltransferases (UGTs). Here, we report that the
      natural variation of rice flavones is mainly determined by OsUGT706D1 (flavone 7
      O-glucosyltransferase) and OsUGT707A2 (flavone 5-O-glucosyltransferase). UV-B
      exposure and transgenic evaluation demonstrate that their allelic variation
      contributes to UV-B tolerance in nature. Biochemical characterization of over 40
      flavonoid UGTs reveals their differential evolution in angiosperms. These
      combined data provide biochemical insight and genetic regulation into flavone
      biosynthesis and additionally suggest that adoption of the positive alleles of
      these genes into breeding programs will likely represent a potential strategy
      aimed at producing stress-tolerant plants.

PMID- 29213049
TI  - Entropic patchiness drives multi-phase coexistence in discotic colloid-depletant
      mixtures.
AB  - Entropy-driven equilibrium phase behaviour of hard particle dispersions can be
      understood from excluded volume arguments only. While monodisperse hard spheres
      only exhibit a fluid-solid phase transition, anisotropic hard particles such as
      rods, discs, cuboids or boards exhibit various multi-phase equilibria. Ordering
      of such anisotropic particles increases the free volume entropy by reducing the
      excluded volume between them. The addition of depletants gives rise to an
      entropic patchiness represented by orientation-dependent attractions resulting in
      non-trivial phase behaviour. We show that free volume theory is a simple, generic
      and tractable framework that enables to incorporate these effects and rationalise
      various experimental findings. Plate-shaped particles constitute the main
      building blocks of clays, asphaltenes and chromonic liquid crystals that find
      widespread use in the food, cosmetics and oil industry. We demonstrate that
      mixtures of platelets and ideal depletants exhibit a strikingly rich phase
      behaviour containing several types of three-phase coexistence areas and even a
      quadruple region with four coexisting phases.

PMID- 29213050
TI  - Hydrogen motion in rutile TiO2.
AB  - Uniaxial-stress experiments have been performed for the 3287- and 2445-cm-1 local
      vibrational modes assigned to the positive charge state of interstitial hydrogen
      [Formula: see text] and deuterium [Formula: see text], respectively, occurring in
      mono-crystalline rutile TiO2. The onset of the defect alignment under the stress
      applied perpendicular to the [001] axis is detected at 165 K (185 K), which
      corresponds to the activation energy of 0.53 eV (0.58 eV) for interstitial
      hydrogen (deuterium). Based on these findings the diffusion constants of
      [Formula: see text] and [Formula: see text] along the [001] axis of TiO2 are
      determined. The experimental data are complemented by density-functional theory
      calculations and compared with the earlier results on the diffusion of [Formula:
      see text]/[Formula: see text] at elevated temperatures up to 700  degrees C. It
      is found that the activation energy value deduced from our low-temperature stress
      measurements yields a very good agreement with the high-temperature data,
      covering a dynamic range of 12 orders of magnitude.

PMID- 29213051
TI  - A robot-aided visuo-motor training that improves proprioception and spatial
      accuracy of untrained movement.
AB  - Proprioceptive function can become enhanced during motor learning. Yet, we have
      incomplete knowledge to what extent proprioceptive function is trainable and how
      a training that enhances proprioception may influence performance in untrained
      motor skills. To address this knowledge gap, healthy young adults (N = 14)
      trained in a visuomotor task that required learners to make increasingly accurate
      wrist movements. Using a robotic exoskeleton coupled with a virtual visual
      environment, participants tilted a virtual table through continuous wrist
      flexion/extension movements with the goal to position a rolling ball on table
      into a target. With learning progress, the level of difficulty increased by
      altering the virtual ball mechanics and the gain between joint movement and ball
      velocity. Before and after training, wrist position sense acuity and spatial
      movement accuracy in an untrained, discrete wrist-pointing task was assessed
      using the same robot. All participants showed evidence of proprioceptive-motor
      learning. Mean position sense discrimination threshold improved by 34%. Wrist
      movement accuracy in the untrained pointing task improved by 27% in 13/14
      participants. This demonstrates that a short sensorimotor training challenging
      proprioception can a) effectively enhance proprioceptive acuity and b) improve
      the accuracy of untrained movement. These findings provide a scientific basis for
      applying such somatosensory-based motor training to clinical populations with
      known proprioceptive dysfunction to enhance sensorimotor performance.

PMID- 29213052
TI  - Exosomes from antigen-pulsed dendritic cells induce stronger antigen-specific
      immune responses than microvesicles in vivo.
AB  - Extracellular vesicles (EV), including exosomes and microvesicles (MV), represent
      a rapidly expanding field of research with diagnostic and therapeutic
      applications. Although many aspects of EV function remain to be revealed and
      broad investigations are warranted, most published findings focus on only one
      vesicle category or a non-separated mix of EVs. In this paper, we investigated
      both MVs and exosomes from Ovalbumin (OVA)-pulsed dendritic cells for their
      immunostimulatory potential side-by-side in vivo. Only exosomes induced antigen
      specific CD8+ T-cells, and were more efficient than MVs in eliciting antigen
      specific IgG production. Further, mainly exosome-primed mouse splenocytes showed
      significant ex vivo interferon gamma production in response to antigen
      restimulation. Exosomes carried high levels of OVA, while OVA in MVs was barely
      detectable, which could explain the more potent antigen-specific response induced
      by exosomes. Moreover, exosomes induced increased germinal center B cell
      proportions, whereas MVs had no such effect. Immunisation with both vesicle types
      combined showed neither inhibitory nor synergistic effects. We conclude that DC
      derived MVs and exosomes differ in their capacity to incorporate antigen and
      induce immune responses. The results are of importance for understanding the role
      of EVs in vivo, and for future design of vesicle-based immunotherapies and
      vaccines.

PMID- 29213053
TI  - The conserved ancient role of chordate PIAS as a multilevel repressor of the NF
      kappaB pathway.
AB  - In vertebrates, PIAS genes encode versatile cellular regulators, with functions
      extremely complex and redundant. Here we try to understand their functions from
      an evolutionary perspective. we evaluate the sequences, expression and molecular
      functions of amphioxus PIAS genes and compare them with their vertebrate
      counterparts. Phylogenetic analysis suggests a single PIAS gene in ancestral
      chordates, which has been duplicated into four families (PIAS1-4) in vertebrates
      by 2R-WGD but remained single in a basal chordate (amphioxus). Amphioxus PIAS
      encodes two variants with and without a Serine/Threonine-rich tail, which are
      retained in human PIAS1-3 but lost in PIAS4. We show that amphioxus PIAS binds C
      terminus of NF-kappaB Rel and blocks the DNA binding activity. In humans, such
      function is retained in PIAS1, altered in PIAS4, and lost in PIAS2-3. Instead,
      PIAS3 has evolved new ability to inhibit Rel by binding RHD and promoting
      SUMOylation. We show that amphioxus PIAS also inhibits NF-kappaB by binding with
      upstream signalling adaptor TICAM-like and MyD88. Finally, we verify that human
      PIAS1, 3 and 4, but not 2, were capable of these newly-discovered functions. Our
      study offers insight into the sub- and neo-functionalization of PIAS genes and
      suggests a conserved ancient role for chordate PIAS in NF-kappaB signalling.

PMID- 29213054
TI  - Polarization response and scaling law of chirality for a nanofibre optical
      interface.
AB  - Two port optical devices couple light to either port dependent on the input
      photon state. An important class of two-port devices is that of evanescently
      coupled interfaces where chirality of photon coupling can lead to important
      technological applications. Here, we perform a fundamental characterization of
      such an interface, reconstructing the two-port polarization response over the
      surface of the Poincare sphere for an optical nanofibre. From this result, we
      derive a chirality measure which is universal, obeying a one parameter scaling
      law independent of the exact parameters of the nanofibre and wavelength of light.
      Additionally, we note that the polarization response differs qualitatively for
      single and multiple coupled emitters, with possible implications for sensing and
      the characterization of waveguide coupled spins.

PMID- 29213055
TI  - Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a
      cholesterol-dependent cytolysin.
AB  - Animal health depends on the ability of immune cells to kill invading pathogens,
      and on the resilience of tissues to tolerate the presence of pathogens.
      Trueperella pyogenes causes tissue pathology in many mammals by secreting a
      cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells.
      Cellular cholesterol is derived from squalene, which is synthesized via the
      mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study
      tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce
      cellular cholesterol increases the resilience of stromal cells to PLO. We first
      verified that depleting cellular cholesterol with methyl-beta-cyclodextrin
      increased the resilience of stromal cells to PLO. We then used siRNA to deplete
      mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors,
      atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR,
      FDPS and FDFT1, respectively. These approaches successfully reduced cellular
      cholesterol abundance, but mevalonate pathway enzymes did not affect cellular
      resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid
      reducing the impact of PLO on cell viability. The present study provides evidence
      that inhibiting FDFT1 increases stromal cell resilience to a cholesterol
      dependent cytolysin.

PMID- 29213056
TI  - A Random Categorization Model for Hierarchical Taxonomies.
AB  - A taxonomy is a standardized framework to classify and organize items into
      categories. Hierarchical taxonomies are ubiquitous, ranging from the
      classification of organisms to the file system on a computer. Characterizing the
      typical distribution of items within taxonomic categories is an important
      question with applications in many disciplines. Ecologists have long sought to
      account for the patterns observed in species-abundance distributions (the number
      of individuals per species found in some sample), and computer scientists study
      the distribution of files per directory. Is there a universal statistical
      distribution describing how many items are typically found in each category in
      large taxonomies? Here, we analyze a wide array of large, real-world datasets -
      including items lost and found on the New York City transit system, library
      books, and a bacterial microbiome - and discover such an underlying commonality.
      A simple, non-parametric branching model that randomly categorizes items and
      takes as input only the total number of items and the total number of categories
      is quite successful in reproducing the observed abundance distributions. This
      result may shed light on patterns in species-abundance distributions long
      observed in ecology. The model also predicts the number of taxonomic categories
      that remain unrepresented in a finite sample.

PMID- 29213057
TI  - A catch-up illusion arising from a distance-dependent perception bias in judging
      relative movement.
AB  - The perception of relative target movement from a dynamic observer is an
      unexamined psychological three body problem. To test the applicability of
      explanations for two moving bodies participants repeatedly judged the relative
      movements of two runners chasing each other in video clips displayed on a
      stationary screen. The chased person always ran at 3 m/s with an observer camera
      following or leading at 4.5, 3, 1.5 or 0 m/s. We harmonized the chaser speed in
      an adaptive staircase to determine the point of subjective equal movement speed
      between runners and observed (i) an underestimation of chaser speed if the
      runners moved towards the viewer, and (ii) an overestimation of chaser speed if
      the runners moved away from the viewer, leading to a catch-up illusion in case of
      equidistant runners. The bias was independent of the richness of available self
      movement cues. Results are inconsistent with computing individual speeds, relying
      on constant visual angles, expansion rates, occlusions, or relative distances but
      are consistent with inducing the impression of relative movement through
      perceptually compressing and enlarging inter-runner distance. This mechanism
      should be considered when predicting human behavior in complex situations with
      multiple objects moving in depth such as driving or team sports.

PMID- 29213058
TI  - Interplay between global and pathway-specific synaptic plasticity in CA1
      pyramidal cells.
AB  - Mechanisms underlying information storage have been depicted for global cell-wide
      and pathway-specific synaptic plasticity. Yet, little is known how these forms of
      plasticity interact to enhance synaptic competition and network stability. We
      examined synaptic interactions between apical and basal dendrites of CA1
      pyramidal neurons in mouse hippocampal slices. Bursts (50 Hz) of three action
      potentials (AP-bursts) paired with preceding presynaptic stimulation in stratum
      radiatum specifically led to LTP of the paired pathway in adult mice (P75). At
      adolescence (P28), an increase in burst frequency (>50 Hz) was required to gain
      timing-dependent LTP. Surprisingly, paired radiatum and unpaired oriens pathway
      potentiated, unless the pre-post delay was shortened from 10 to 5 ms, which
      selectively potentiated paired radiatum pathway, since unpaired oriens pathway
      decreased back to baseline. Conversely, the exact same 5 ms pairing in stratum
      oriens potentiated both pathways, as did AP-bursts alone, which potentiated
      synaptic efficacy as well as current-evoked postsynaptic spiking. L-type voltage
      gated Ca2+ channels were involved in mediating synaptic potentiation in oriens,
      whereas NMDA and adenosine receptors counteracted unpaired stratum oriens
      potentiation following pairing in stratum radiatum. This asymmetric plasticity
      uncovers important insights into alterations of synaptic efficacy and intrinsic
      neuronal excitability for pathways that convey hippocampal and extra-hippocampal
      information.

PMID- 29213059
TI  - A Comprehensive Assessment of the Genetic Determinants in Salmonella Typhimurium
      for Resistance to Hydrogen Peroxide Using Proteogenomics.
AB  - Salmonella is an intracellular pathogen infecting a wide range of hosts and can
      survive in macrophages. An essential mechanism used by macrophages to eradicate
      Salmonella is production of reactive oxygen species. Here, we used proteogenomics
      to determine the candidate genes and proteins that have a role in resistance of
      S. Typhimurium to H2O2. For Tn-seq, a saturated Tn5 insertion library was grown
      in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets
      of overlapping genes required for resistance of S. Typhimurium to H2O2L and
      H2O2H, and the results were validated via phenotypic evaluation of 50 selected
      mutants. The enriched pathways for H2O2 resistance included DNA repair, aromatic
      amino acid biosynthesis (aroBK), Fe-S cluster biosynthesis, iron homeostasis and
      a putative iron transporter system (ybbKLM), and H2O2 scavenging enzymes.
      Proteomics revealed that the majority of essential proteins, including ribosomal
      proteins, were downregulated upon exposure to H2O2. On the contrary, a subset of
      conditionally essential proteins identified by Tn-seq were analyzed by targeted
      proteomics, and 70% of them were upregulated by H2O2. The identified genes will
      deepen our understanding on S. Typhimurium survival mechanisms in macrophages,
      and can be exploited to develop new antimicrobial drugs.

PMID- 29213060
TI  - Structural characterization of site-modified nanocapsid with monodispersed gold
      clusters.
AB  - Hepatitis E Virus-like particles self-assemble in to noninfectious nanocapsids
      that are resistant to proteolytic/acidic mucosal delivery conditions. Previously,
      the nanocapsid was engineered to specifically bind and enter breast cancer cells,
      where successful tumor targeting was demonstrated in animal models. In the
      present study, the nanocapsid surface was modified with a solvent-exposed
      cysteine to conjugate monolayer protected gold nanoclusters (AuNC). Unlike
      commercially available gold nanoparticles, AuNCs monodisperse in water and are
      composed of a discrete number of gold atoms, forming a crystalline gold core.
      Au102 pMBA44 (Au102) was an ideal conjugate given its small 2.5 nm size and
      detectability in cryoEM. Au102 was bound directly to nanocapsid surface cysteines
      via direct ligand exchange. In addition, Au102 was functionalized with a
      maleimide linker (Au102_C6MI) for maleimide-thiol conjugation to nanocapsid
      cysteines. The AuNC-bound nanocapsid constructs were conjugated in various
      conditions. We found Au102_C6MI to bind nanocapsid more efficiently, while Au102
      remained more soluble over time. Nanocapsids conjugated to Au102_C6MI were imaged
      in cryoEM for single particle reconstruction to localize AuNC position on the
      nanocapsid surface. We resolved five unique high intensity volumes that formed a
      ring-shaped density at the 5-fold symmetry center. This finding was further
      supported by independent rigid modeling.

PMID- 29213061
TI  - First-principles study of nonmetal doped monolayer MoSe2 for tunable electronic
      and photocatalytic properties.
AB  - Recently, two dimensional transition metal dichalcogenides become popular
      research topics because of their unique crystal and electronic structure. In this
      work, the geometrical structure, electronic, electrical transport, redox
      potentials and photocatalytic properties of nonmetal (H, B, C, Si, N, P, As, O,
      S, Te, F, Cl, Br and I) doped monolayer MoSe2 were investigated by first
      principle calculations. The binding energy indicates that nonmetal doped MoSe2
      are energetically favorable compared to Se vacancies, except B- and C-doped. We
      have found that nonmetal dopants with an even number of valence electrons doped
      MoSe2 have p-type conductivity. On the contrary, nonmetal dopants with an odd
      number of valence electrons doped MoSe2 have p-type or n-type conductivity; and
      they have better photocatalytic performance.

PMID- 29213062
TI  - Nutrient resorption or accumulation of desert plants with contrasting sodium
      regulation strategies.
AB  - Desert plants are thought to rely more heavily on nutrient resorption due to the
      infertile soil. However, little is known regarding the phylogenetic effects on
      this traits, specifically for halophytes. Here we determined contents of nitrogen
      (N), phosphorus (P), potassium (K), sodium (Na), calcium (Ca) and magnesium (Mg)
      in 36 desert plants in a hyper-arid environment. The patterns of resorption or
      accumulation of the six elements were compared among plant groups with diverse
      leaf Na regulation strategies: i.e., euhalophytes (Eu), secretohalophytes (Se),
      pseudohalophytes (Ps) and glycophytes (Gl). Overall, N, P, K presented strict
      resorption across all groups, but no more efficient than global estimations. Ca
      and Mg tended to be resorbed less or accumulated during leaf senescence.
      Significant phylogenetic signal of both leaf Na content and plant group implies
      the pivotal role of Na regulation in the adaptation of plants to desert
      environment. Resorption proficiency, rather than resorption efficiency, is more
      phylogenetically conservative and more relevant to leaf functional traits.

PMID- 29213063
TI  - Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective
      study of induction therapy for primary central nervous system lymphoma in
      Chinese.
AB  - We performed a retrospective study of 49 patients with newly diagnosed primary
      central nervous system lymphoma (PCNSL), to compare the efficacy and safety of
      different high-dose methotrexate (HD-MTX) based systemic chemotherapy regimens as
      induction therapy. 25 patients received AB +/- R alternative regimen (consist
      methotrexate, ifosfamide, vindesine, dexamethasone, carmustine and teniposide),
      while others received HD-MTX +/- R regimen. The complete response rate and
      overall response rate of AB +/- R group and HD-MTX +/- R group were 36.83% vs.
      33.33%, and 68.42% vs. 71.43%, while the 2-year OS and PFS rate were 71.43% vs.
      74.62%, and 42.86% vs. 54.64%, respectively. In Age > 60 subgroup, the 2-year OS
      and PFS rate of AB +/- R group and HD-MTX +/- R group were 81.82% vs. 33.33%, and
      54.55% vs. 33.33%. No significant differences were found in grade 3 or 4 toxicity
      rate. Generally, HD-MTX +/- R regimen was not inferior to AB +/- R alternative
      regimen, but AB +/- R alternative regimen seemed achieving more survival benefits
      in the elderly. We suggest to adjust HD-MTX +/- R regimen by changing the dose
      reduction strategy especially in elderly patients and adding other powerful drugs
      that can well penetrate blood-brain barrier to improve the efficacy.

PMID- 29213064
TI  - Growth of Graphene/h-BN Heterostructures on Recyclable Pt Foils by One-Batch
      Chemical Vapor Deposition.
AB  - High-quality large-area graphene/h-BN vertical heterostructures are promising
      building blocks for many viable applications such as energy
      harvesting/conversion, electronics and optoelectronics. Here, we successfully
      grew high-quality large-area graphene/h-BN vertical heterostructures on Pt foils
      by one-batch low-pressure chemical vapor deposition (LPCVD). We obtained the high
      quality of about 200-um-wide graphene/h-BN film having uniform layer thickness.
      Moreover, the obtained graphene/h-BN heterostructures exhibited field effect
      mobility of up to 7,200 cm2V-1s-1 at room temperature. These results suggest that
      such graphene/h-BN heterostructures on recyclable Pt foils grown by LPCVD are
      promising for high-performance graphene-based electronics.

PMID- 29213065
TI  - Modulation Of Microtubule Acetylation By The Interplay Of TPPP/p25, SIRT2 And New
      Anticancer Agents With Anti-SIRT2 Potency.
AB  - The microtubule network exerts multifarious functions controlled by its
      decoration with various proteins and post-translational modifications. The
      disordered microtubule associated Tubulin Polymerization Promoting Protein
      (TPPP/p25) and the NAD+-dependent tubulin deacetylase sirtuin-2 (SIRT2) play key
      roles in oligodendrocyte differentiation by acting as dominant factors in the
      organization of myelin proteome. Herein, we show that SIRT2 impedes the TPPP/p25
      promoted microtubule assembly independently of NAD+; however, the TPPP/p25
      assembled tubulin ultrastructures were resistant against SIRT2 activity. TPPP/p25
      counteracts the SIRT2-derived tubulin deacetylation producing enhanced
      microtubule acetylation. The inhibition of the SIRT2 deacetylase activity by
      TPPP/p25 is evolved by the assembly of these tubulin binding proteins into a
      ternary complex, the concentration-dependent formation of which was quantified by
      experimental-based mathematical modelling. Co-localization of the SIRT2-TPPP/p25
      complex on the microtubule network was visualized in HeLa cells by
      immunofluorescence microscopy using Bimolecular Fluorescence Complementation. We
      also revealed that a new potent SIRT2 inhibitor (MZ242) and its proteolysis
      targeting chimera (SH1) acting together with TPPP/p25 provoke microtubule
      hyperacetylation, which is coupled with process elongation only in the case of
      the degrader SH1. Both the structural and the functional effects manifesting
      themselves by this deacetylase proteome could lead to the fine-tuning of the
      regulation of microtubule dynamics and stability.

PMID- 29213066
TI  - CRISPR/Cas9 mediated mutation of mouse IL-1alpha nuclear localisation sequence
      abolishes expression.
AB  - Inflammation is a host defense process against infection. Inflammatory mediators
      include cytokines of the interleukin-1 family, such as IL-1alpha and IL-1beta.
      Unlike IL-1beta, IL-1alpha carries an N-terminal nuclear localisation sequence
      (NLS) and is trafficked to the nucleus. The importance of IL-1alpha nuclear
      localisation is poorly understood. Here, we used CRISPR/Cas9 to make inactivating
      mutations to the NLS on the Il1a gene. A colony of NLS mutant mice was
      successfully generated with precise knock-in mutations to incapacitate NLS
      function. NLS mutant mice had no gross changes in immunophenotype or inflammatory
      response but, surprisingly, failed to express IL-1alpha. We deduced that, in
      making specific mutations in the Il1a gene, we also mutated a long-noncoding
      (lnc)RNA in the complementary strand which has cis-regulatory transcriptional
      control of the Il1a gene itself. The mutations generated in the Il1a gene also
      result in mutation of the lncRNA sequence and a predicted alteration of its
      secondary structure, potentially explaining a subsequent failure to function as a
      transcriptional activator of Il1a expression. Thus, lncRNA secondary structure
      may regulate IL-1alpha expression. Our results serve as a cautionary note that
      CRISPR -mediated genome editing without full knowledge of genomic context can
      result in unexpected, yet potentially informative observations.

PMID- 29213067
TI  - Not all observed actions are perceived equally.
AB  - Action observation is the visual process analyzing the actions of others to
      determine their goals and how the actor's body (part) movements permit attaining
      those goals. Our recent psychophysical study demonstrated that 1) observed action
      (OA) perception differs from shape perception in viewpoint and duration
      dependence, and 2) accuracy and reaction times of OA discrimination are fitted by
      the proportional-rate diffusion model whereby a sensory stage provides noisy
      evidence that is accumulated up to a criterion or bound by a decision stage. That
      study was devoted to observation of manipulative actions, following a general
      trend of the field. Recent functional imaging studies of action observation,
      however, have established various OA classes as separate entities with processing
      routes involving distinct posterior parietal cortex (PPC) regions. Here, we show
      that the diffusion model applies to multiple OA classes. Even more importantly,
      the observers' ability to discriminate exemplars of a given class differs
      considerably between OA classes and these performance differences correspond to
      differences in model parameters. In particular, OA classes differ in the bound
      parameter which we propose may reflect an urgency signal originating in the PPC
      regions corresponding to the sensory stages of different OA classes.

PMID- 29213068
TI  - Comparative analysis of double-stranded RNA degradation and processing in
      insects.
AB  - RNA interference (RNAi) based methods are being developed for pest management. A
      few products for control of coleopteran pests are expected to be commercialized
      soon. However, variability in RNAi efficiency among insects is preventing the
      widespread use of this technology. In this study, we conducted research to
      identify reasons for variability in RNAi efficiency among thirty-seven (37)
      insects belonging to five orders. Studies on double-stranded RNA (dsRNA)
      degradation by dsRNases and processing of labeled dsRNA to siRNA showed that both
      dsRNA degradation and processing are variable among insects belonging to
      different orders as well as among different insect species within the same order.
      We identified homologs of key RNAi genes in the genomes of some of these insects
      and studied their domain architecture. These data suggest that dsRNA digestion by
      dsRNases and its processing to siRNAs in the cells are among the major factors
      contributing to differential RNAi efficiency reported among insects.

PMID- 29213069
TI  - Preparation of Permanent Magnetic Resin Crosslinking by Diallyl Itaconate and Its
      Adsorptive and Anti-fouling Behaviors for Humic Acid Removal.
AB  - In this research, a series of permanent magnetic anion exchange resins (MAERs)
      were prepared by polymerizing glycidyl methacrylate monomer and crosslinking
      diallyl itaconate (DAI) and divinylbenzene. The properties and performances of
      these novel MAERs were systematically characterized and evaluated for humic acid
      (HA) adsorption by batch experiments. With the increase of DAI content from 0 to
      15%, the moisture of MAERs was elevated from 50.23% to 68.53%, along with the
      adsorption capacity increasing from 2.57 to 3.14 mmol g-1. As the concentrations
      of co-existing cation (Ca2+ and Mg2+) increased, the adsorption amounts of HA
      dropped drastically at first and increased a little at high cation
      concentrations. Although ion exchange was the primary mechanism for HA
      adsorption, other physical interactions and electrostatic attraction between HA
      molecules and newly formed oxonium group also played significant roles for HA
      adsorption. The MAERs could be efficiently regenerated by a mixture of NaCl/NaOH
      solution (10%/1%), and notably, the MAER-3 with the highest DAI content displayed
      unapparent loss of adsorption capacity during twenty-one successive adsorption
      desorption cycles. These results suggested a novel resin adsorbent for its
      excellent performances on adsorption, regeneration, and sedimentation in water
      treatment for natural organic matter removal.

PMID- 29213070
TI  - Sensitivity analysis of coupled processes and parameters on the performance of
      enhanced geothermal systems.
AB  - 3-D modeling of coupled thermo-hydro-mechanical (THM) processes in enhanced
      geothermal systems using the control volume finite element code was done. In a
      first, a comparative analysis on the effects of coupled processes, operational
      parameters and reservoir parameters on heat extraction was conducted. We found
      that significant temperature drop and fluid overpressure occurred inside the
      reservoirs/fracture that affected the transport behavior of the fracture. The
      spatio-temporal variations of fracture aperture greatly impacted the thermal
      drawdown and consequently the net energy output. The results showed that maximum
      aperture evolution occurred near the injection zone instead of the production
      zone. Opening of the fracture reduced the injection pressure required to
      circulate a fixed mass of water. The thermal breakthrough and heat extraction
      strongly depend on the injection mass flow rate, well distances, reservoir
      permeability and geothermal gradients. High permeability caused higher water
      loss, leading to reduced heat extraction. From the results of TH vs THM process
      simulations, we conclude that appropriate coupling is vital and can impact the
      estimates of net heat extraction. This study can help in identifying the critical
      operational parameters, and process optimization for enhanced energy extraction
      from a geothermal system.

PMID- 29213072
TI  - Characterization of Large Copy Number Variation in Mexican Type 2 Diabetes
      subjects.
AB  - The effect of Copy Number Variants (CNVs) on Type 2 Diabetes (T2D) remains little
      explored. The present study characterized large rare CNVs in 686 T2D and 194 non
      T2D subjects of Mexican ancestry genotyped using the Affymetrix Genome-Wide Human
      SNP array 5.0. Rare CNVs with >= 100 kb length were identified using a stringent
      strategy based on merging CNVs calls generated using Birdsuit, iPattern and
      PennCNV algorithms. We applied three different strategies to evaluate the
      distribution of CNVs in the T2D and non-T2D samples: 1) Burden analysis, 2)
      Identification of CNVs in loci previously associated to T2D, and 3)
      Identification of CNVs observed only in the T2D group. In the CNV burden
      analysis, the T2D group showed a higher proportion of CNVs, and also a higher
      proportion of CNVs overlapping at least one gene than the non T2D group. Five of
      the six loci previously associated with T2D had duplications or deletions in the
      T2D sample, but not the non-T2D sample. A gene-set analysis including genes with
      CNVs observed only in the T2D group highlighted gene-sets related with sensory
      perception (olfactory receptors, OR) and phenylpyruvate tautomerase/dopachrome
      isomerase activity (MIF and DDT genes).

PMID- 29213071
TI  - GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes
      previously identified loci and identifies population-specific signals.
AB  - QT interval prolongation is a heritable risk factor for ventricular arrhythmias
      and can predispose to sudden death. Most genome-wide association studies (GWAS)
      of QT were performed in European ancestral populations, leaving other groups
      uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using
      data on 15,997 participants from four studies. Study-specific summary results of
      the association between 1000 Genomes Project (1000G) imputed SNPs and
      electrocardiographically measured QT were combined using fixed-effects meta
      analysis. We identified 41 genome-wide significant SNPs that mapped to 13
      previously identified QT loci. Conditional analyses distinguished six secondary
      signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1).
      Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six
      secondary signals with previously reported index SNPs in 1000G super populations
      suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and
      population-specific. Finally, of the 42 suggestively associated loci, AJAP1 was
      suggestively associated with QT in a prior East Asian GWAS; in contrast BVES and
      CAP2 murine knockouts caused cardiac conduction defects. Our results indicate
      that whereas the same loci influence QT across populations, population-specific
      variation exists, motivating future trans-ethnic and ancestrally diverse QT GWAS.

PMID- 29213075
TI  - Suppression of Stochastic Domain Wall Pinning Through Control of Gilbert Damping.
AB  - Finite temperature micromagnetic simulations were used to investigate the
      magnetisation structure, propagation dynamics and stochastic pinning of domain
      walls in rare earth-doped Ni80Fe20 nanowires. We first show how the increase of
      the Gilbert damping, caused by the inclusion rare-earth dopants such as holmium,
      acts to suppress Walker breakdown phenomena. This allows domain walls to maintain
      consistent magnetisation structures during propagation. We then employ finite
      temperature simulations to probe how this affects the stochastic pinning of
      domain walls at notch-shaped artificial defect sites. Our results indicate that
      the addition of even a few percent of holmium allows domain walls to pin with
      consistent and well-defined magnetisation configurations, thus suppressing
      dynamically-induced stochastic pinning/depinning phenomena. Together, these
      results demonstrate a powerful, materials science-based solution to the problems
      of stochastic domain wall pinning in soft ferromagnetic nanowires.

PMID- 29213073
TI  - Reversible silencing of lumbar spinal interneurons unmasks a task-specific
      network for securing hindlimb alternation.
AB  - Neural circuitry in the lumbar spinal cord governs two principal features of
      locomotion, rhythm and pattern, which reflect intra- and interlimb movement.
      These features are functionally organized into a hierarchy that precisely
      controls stepping in a stereotypic, speed-dependent fashion. Here, we show that a
      specific component of the locomotor pattern can be independently manipulated.
      Silencing spinal L2 interneurons that project to L5 selectively disrupts hindlimb
      alternation allowing a continuum of walking to hopping to emerge from the
      otherwise intact network. This perturbation, which is independent of speed and
      occurs spontaneously with each step, does not disrupt multi-joint movements or
      forelimb alternation, nor does it translate to a non-weight-bearing locomotor
      activity. Both the underlying rhythm and the usual relationship between speed and
      spatiotemporal characteristics of stepping persist. These data illustrate that
      hindlimb alternation can be manipulated independently from other core features of
      stepping, revealing a striking freedom in an otherwise precisely controlled
      system.

PMID- 29213074
TI  - Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal
      effects.
AB  - Cryptococcus neoformans is an encapsulated fungal pathogen that causes
      cryptococcosis, which is a major opportunistic infection in immunosuppressed
      individuals. Mammalian beta-galactoside-binding protein Galectin-3 (Gal-3)
      modulates the host innate and adaptive immunity, and plays significant roles
      during microbial infections including some fungal diseases. Here we show that
      this protein plays a role also in C. neoformans infection. We find augmented Gal
      3 serum levels in human and experimental infections, as well as in spleen, lung,
      and brain tissues of infected mice. Gal-3-deficient mice are more susceptible to
      cryptococcosis than WT animals, as demonstrated by the higher fungal burden and
      lower animal survival. In vitro experiments show that Gal-3 inhibits fungal
      growth and exerts a direct lytic effect on C. neoformans extracellular vesicles
      (EVs). Our results indicate a direct role for Gal-3 in antifungal immunity
      whereby this molecule affects the outcome of C. neoformans infection by
      inhibiting fungal growth and reducing EV stability, which in turn could benefit
      the host.

PMID- 29213076
TI  - Strain induced band inversion and topological phase transition in methyl
      decorated stanene film.
AB  - The researches for new quantum spin Hall (QSH) insulators with large bulk energy
      gap are of much significance for their practical applications at room temperature
      in electronic devices with low-energy consumption. By means of first-principles
      calculations, we proposed that methyl-decorated stanene (SnCH3) film can be tuned
      into QSH insulator under critical tensile strain of 6%. The nonzero topological
      invariant and helical edge states further confirm the nontrivial nature in
      stretched SnCH3 film. The topological phase transition originates from the s-p xy
      type band inversion at the Gamma point with the strain increased. The spin
      orbital coupling (SOC) induces a large band gap of ~0.24 eV, indicating that
      SnCH3 film under strain is a quite promising material to achieve QSH effect. The
      proper substrate, h-BN, finally is presented to support the SnCH3 film with
      nontrivial topology preserved.

PMID- 29213078
TI  - Functional status of microvascular vasomotion is impaired in spontaneously
      hypertensive rat.
AB  - Accumulating evidence demonstrates that microcirculation plays a role in the
      pathogenesis of hypertension. In the current study, we demonstrated that
      pancreatic islet microvascular vasomotion of spontaneously hypertensive rats
      (SHRs) lost the ability to regulate blood flow perfusion and exhibited a lower
      microvascular blood perfusion pattern which was negative correlated with blood
      glucose level. SHRs administrated with insulin revealed an improvement of
      pancreatic islet microvascular vasomotion and blood perfusion pattern. In vitro,
      the expressions of endothelial nitric oxide synthase (eNOS) and phospho
      eNOSser1177 (p-eNOSser1177) were significantly decreased in high glucose exposed
      islet endothelial cells (iECs), accompanied with a higher ratio of eNOS monomer
      to eNOS dimer and a significantly increased malondialdehyde and nitrite levels.
      Meanwhile, barrier function, tube formation and migration capacities of high
      glucose exposed iECs were significantly inhibited. In contrast, iECs dysfunction
      induced by glucose toxicity and oxidative stress was attenuated or improved by
      supplement with insulin, L-arginine and beta-mercaptoethanol. In summary, our
      findings suggest that functional status of pancreatic islet microvascular
      vasomotion is impaired in SHRs and provide evidence that treatment with insulin,
      L-arginine and beta-mercaptoethanol improves endothelium-dependent microvascular
      vasomotion and meliorates iECs function due to anti-hyperglycemic and anti
      oxidative effects, partly through mechanism involving regulation of eNOS and p
      eNOSser1177.

PMID- 29213077
TI  - Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in
      contextual fear consolidation.
AB  - Antibodies have enormous therapeutic and biotechnology potential. G protein
      coupled receptors (GPCRs), the main targets in drug development, are of major
      interest in antibody development programs. Metabotropic glutamate receptors are
      dimeric GPCRs that can control synaptic activity in a multitude of ways. Here we
      identify llama nanobodies that specifically recognize mGlu2 receptors, among the
      eight subtypes of mGluR subunits. Among these nanobodies, DN10 and 13 are
      positive allosteric modulators (PAM) on homodimeric mGlu2, while DN10 displays
      also a significant partial agonist activity. DN10 and DN13 have no effect on
      mGlu2-3 and mGlu2-4 heterodimers. These PAMs enhance the inhibitory action of the
      orthosteric mGlu2/mGlu3 agonist, DCG-IV, at mossy fiber terminals in the CA3
      region of hippocampal slices. DN13 also impairs contextual fear memory when
      injected in the CA3 region of hippocampal region. These data highlight the
      potential of developing antibodies with allosteric actions on GPCRs to better
      define their roles in vivo.

PMID- 29213080
TI  - From the Age of 5 Humans Decide Economically, Whereas Crows Exhibit Individual
      Preferences.
AB  - Human societies greatly depend on tools, which spare us considerable time and
      effort. Humans might have evolved a bias to employ tools, using them even when
      they are unnecessary. This study aimed to investigate whether adult humans and a
      distantly related habitually tool-using vertebrate species, the New Caledonian
      crow (Corvus moneduloides), use tools depending on their necessity. In addition,
      children aged 3 to 5 years were examined to investigate the developmental
      pattern. The task involved choosing between using a body part (i.e. crows: beak;
      humans: hand) or a tool for retrieving a reward from a box. All subjects were
      tested in two conditions. In the Body+/Tool- condition, using the body was more
      efficient than using the tool, and conversely in the Body-/Tool+ condition. Our
      results suggest that the capacity to employ tools economically develops late in
      humans. Crows, however, failed to choose economically. At the individual level,
      some subjects exhibited striking individual preferences for either using a tool
      or their beak throughout the task. Whether such biases depend on individual
      experience or whether they are genetically determined remains to be investigated.
      Our findings provide new insights about tool use and its cognitive implementation
      in two outstanding tool-using taxa.

PMID- 29213079
TI  - Human CD26high T cells elicit tumor immunity against multiple malignancies via
      enhanced migration and persistence.
AB  - CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of
      human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we
      exhibit that CD26 identifies three T helper subsets with distinct immunological
      properties in both healthy individuals and cancer patients. Although CD26neg T
      cells possess a regulatory phenotype, CD26int T cells are mainly naive and
      CD26high T cells appear terminally differentiated and exhausted. Paradoxically,
      CD26high T cells persist in and regress multiple solid tumors following adoptive
      cell transfer. Further analysis revealed that CD26high cells have a rich
      chemokine receptor profile (including CCR2 and CCR5), profound cytotoxicity
      (Granzyme B and CD107A), resistance to apoptosis (c-KIT and Bcl2), and enhanced
      stemness (beta-catenin and Lef1). These properties license CD26high T cells with
      a natural capacity to traffic to, regress and survive in solid tumors.
      Collectively, these findings identify CD4+ T cell subsets with properties
      critical for improving cancer immunotherapy.

PMID- 29213082
TI  - Features of electronic and lattice mechanisms of transboundary heat transfer in
      multilayer nanolaminate TiAlN/Ag coatings.
AB  - Plasmon resonance heterogeneities were identified and studied along Ag and TiAlN
      layers within a multilayer stack in nanolaminate TiAlN/Ag coatings. For this
      purpose, a high-resolution plasmon microscopy was used. The plasmons intensity,
      energy, and depth of interface plasmon-polariton penetration were studied by
      scanning reflected electron energy loss spectroscopy. The heat conductivity of
      such metal-insulator-metal (MIM) nanolaminate coatings was measured by laser
      reflectometry. Dependencies of thermal conductivity coefficient of coatings, MIM
      interfaces, and resistivity of Ag layers as a function of the Ag-TiAlN bilayer
      thickness were calculated on the basis of experimental data. The contribution of
      plasmon resonance confinement to the abnormal lower thermal conductivity in the
      MIM metamaterial with Ag layer thickness below 25 nm is discussed. In particular,
      the results highlight the relevant role of different heat transfer mechanisms
      between MI and IM interfaces: asymmetry of plasmon-polariton interactions on
      upper and lower boundaries of Ag layer and asymmetry of LA and TA phonons
      propagation through interfaces.

PMID- 29213081
TI  - Pak2 is essential for the function of Foxp3+ regulatory T cells through
      maintaining a suppressive Treg phenotype.
AB  - Foxp3, a key transcription factor that drives lineage differentiation of
      regulatory T cells (Tregs), was thought to imprint a unique and irreversible
      genetic signature within Tregs. Recent evidence, however, suggests that loss or
      attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector
      T cells capable of producing proinflammatory cytokines. Herein, we report that
      the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining
      Treg stability and suppressive function. Loss of Pak2, specifically in Tregs,
      resulted in reduced expression of multiple Treg functional molecules, including
      Foxp3, CD25, Nrp-1 and CTLA-4, coupled with a loss of Treg suppressive function
      in vitro and in vivo. Interestingly, Pak2-deficient Tregs gained expression of
      Th2-associated cytokines and the transcription factor, Gata3, becoming Th2-like
      cells, explaining their inability to regulate immune responses. Collectively,
      these findings suggest Pak2 as an important signaling molecule for guarding
      against aberrant immune responses through regulating the stability of Foxp3+
      Tregs and maintaining a suppressive Treg phenotype.

PMID- 29213083
TI  - Automated Interpretation and Extraction of Topographic Information from Time of
      Flight Secondary Ion Mass Spectrometry Data.
AB  - Time of flight secondary ion mass spectrometry (ToF-SIMS) is a powerful surface
      sensitive characterization tool allowing the imaging of chemical properties over
      a wide range of organic and inorganic material systems. This technique allows
      precise studies of chemical composition with sub-100-nm lateral and nanometer
      depth spatial resolution. However, comprehensive interpretation of ToF-SIMS
      results is challenging because of the very large data volume and high
      dimensionality. Furthermore, investigation of samples with pronounced
      topographical features is complicated by systematic and measureable shifts in the
      mass spectrum. In this work we developed an approach for the interpretation of
      the ToF-SIMS data, based on the advanced data analytics. Along with
      characterization of the chemical composition, our approach allows extraction of
      the sample surface morphology from a time of flight registration technique. This
      approach allows one to perform correlated investigations of surface morphology,
      biological function, and chemical composition of Arabidopsis roots.

PMID- 29213084
TI  - Emerging Role for the PERK/eIF2alpha/ATF4 in Human Cutaneous Leishmaniasis.
AB  - Leishmania parasites utilize adaptive evasion mechanisms in infected macrophages
      to overcome host defenses and proliferate. We report here that the
      PERK/eIF2alpha/ATF4 signaling branch of the integrated endoplasmic reticulum
      stress response (IERSR) is activated by Leishmania and this pathway is important
      for Leishmania amazonensis infection. Knocking down PERK or ATF4 expression or
      inhibiting PERK kinase activity diminished L. amazonensis infection. Knocking
      down ATF4 decreased NRF2 expression and its nuclear translocation, reduced HO-1
      expression and increased nitric oxide production. Meanwhile, the increased
      expression of ATF4 and HO-1 mRNAs were observed in lesions derived from patients
      infected with the prevalent related species L.(V.) braziliensis. Our data
      demonstrates that Leishmania parasites activate the PERK/eIF2alpha/ATF-4 pathway
      in cultured macrophages and infected human tissue and that this pathway is
      important for parasite survival and progression of the infection.

PMID- 29213085
TI  - Effective in vivo gene delivery with reduced toxicity, achieved by charge and
      fatty acid -modified cell penetrating peptide.
AB  - Non-viral gene delivery systems have gained considerable attention as a promising
      alternative to viral delivery to treat diseases associated with aberrant gene
      expression. However, regardless of extensive research, only a little is known
      about the parameters that underline in vivo use of the nanoparticle-based
      delivery vectors. The modest efficacy and low safety of non-viral delivery are
      the two central issues that need to be addressed. We have previously
      characterized an efficient cell penetrating peptide, PF14, for in vivo
      applications. In the current work, we first develop an optimized formulation of
      PF14/pDNA nanocomplexes, which allows removal of the side-effects without
      compromising the bioefficacy in vivo. Secondly, based on the physicochemical
      complex formation studies and biological efficacy assessments, we develop a
      series of PF14 modifications with altered charge and fatty acid content. We show
      that with an optimal combination of overall charge and hydrophobicity in the
      peptide backbone, in vivo gene delivery can be augmented. Further combined with
      the safe formulation, systemic gene delivery lacking any side effects can be
      achieved.

PMID- 29213086
TI  - 3D microniches reveal the importance of cell size and shape.
AB  - Geometrical cues have been shown to alter gene expression and differentiation on
      2D substrates. However, little is known about how geometrical cues affect cell
      function in 3D. One major reason for this lack of understanding is rooted in the
      difficulties of controlling cell geometry in a complex 3D setting and for long
      periods of culture. Here, we present a robust method to control cell volume and
      shape of individual human mesenchymal stem cells (hMSCs) inside 3D microniches
      with a range of different geometries (e.g., cylinder, triangular prism, cubic,
      and cuboid). We find that the actin filaments, focal adhesions, nuclear shape,
      YAP/TAZ localization, cell contractility, nuclear accumulation of histone
      deacetylase 3, and lineage selection are all sensitive to cell volume. Our 3D
      microniches enable fundamental studies on the impact of biophysical cues on cell
      fate, and have potential applications in investigating how multicellular
      architectures organize within geometrically well-defined 3D spaces.

PMID- 29213087
TI  - Warhead biosynthesis and the origin of structural diversity in hydroxamate
      metalloproteinase inhibitors.
AB  - Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the
      chelation of metal ions in the catalytic center of target enzymes. Actinonin and
      matlystatins are  potent metalloproteinase inhibitors that comprise rare N
      hydroxy-2-pentyl-succinamic acid warheads. Here we report the identification and
      characterization of their biosynthetic pathways. By gene cluster comparison and a
      combination of precursor feeding studies, heterologous pathway expression and
      gene deletion experiments we are able to show that the N-hydroxy-alkyl-succinamic
      acid warhead is generated by an unprecedented variation of the ethylmalonyl-CoA
      pathway. Moreover, we present evidence that the remarkable structural diversity
      of matlystatin congeners originates from the activity of a decarboxylase
      dehydrogenase enzyme with high similarity to enzymes that form epoxyketones. We
      further exploit this mechanism to direct the biosynthesis of non-natural
      matlystatin derivatives. Our work paves the way for follow-up studies on these
      fascinating pathways and allows the identification of new protease inhibitors by
      genome mining.

PMID- 29213088
TI  - NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous
      cell carcinoma.
AB  - Chromatin modifying enzymes are frequently mutated in cancer, resulting in
      widespread epigenetic deregulation. Recent reports indicate that inactivating
      mutations in the histone methyltransferase NSD1 define an intrinsic subtype of
      head and neck squamous cell carcinoma (HNSC) that features pronounced DNA
      hypomethylation. Here, we describe a similar hypomethylated subtype of lung
      squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations
      and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated
      at the DNA methylation and gene expression levels, featuring ectopic expression
      of developmental transcription factors and genes that are also hypomethylated in
      Sotos syndrome, a congenital disorder caused by germline NSD1 mutations. Further,
      the NSD1 subtype of HNSC displays an 'immune cold' phenotype characterized by low
      infiltration of tumor-associated leukocytes, particularly macrophages and CD8+ T
      cells, as well as low expression of genes encoding the immunotherapy target PD-1
      immune checkpoint receptor and its ligands. Using an in vivo model, we
      demonstrate that NSD1 inactivation results in reduced T cell infiltration into
      the tumor microenvironment, implicating NSD1 as a tumor cell-intrinsic driver of
      an immune cold phenotype. NSD1 inactivation therefore causes epigenetic
      deregulation across cancer sites, and has implications for immunotherapy.

PMID- 29213089
TI  - Formation of a transient amorphous solid in low density aqueous charged sphere
      suspensions.
AB  - Colloidal glasses formed from hard spheres, nearly hard spheres, ellipsoids and
      platelets or their attractive variants, have been studied in great detail.
      Complementing and constraining theoretical approaches and simulations, the many
      different types of model systems have significantly advanced our understanding of
      the glass transition in general. Despite their early prediction, however, no
      experimental charged sphere glasses have been found at low density, where the
      competing process of crystallization prevails. We here report the formation of a
      transient amorphous solid formed from charged polymer spheres suspended in
      thoroughly deionized water at volume fractions of 0.0002-0.01. From optical
      experiments, we observe the presence of short-range order and an enhanced shear
      rigidity as compared to the stable polycrystalline solid of body centred cubic
      structure. On a density dependent time scale of hours to days, the amorphous
      solid transforms into this stable structure. We further present preliminary
      dynamic light scattering data showing the evolution of a second slow relaxation
      process possibly pointing to a dynamic heterogeneity known from other colloidal
      glasses and gels. We compare our findings to the predicted phase behaviour of
      charged sphere suspensions and discuss possible mechanisms for the formation of
      this peculiar type of colloidal glass.

PMID- 29213090
TI  - Evaluation of short interval cortical inhibition and intracortical facilitation
      from the dorsolateral prefrontal cortex in patients with schizophrenia.
AB  - GABAergic and glutamatergic dysfunction in the dorsolateral prefrontal cortex
      (DLPFC) are thought to be the core pathophysiological mechanisms of
      schizophrenia. Recently, we have established a method to index these functions
      from the DLPFC using the paired transcranial magnetic stimulation (TMS) paradigms
      of short interval intracortical inhibition (SICI) and facilitation (ICF) combined
      with electroencephalography (EEG). In this study, we aimed to evaluate
      neurophysiological indicators related to GABAA and glutamate receptor-mediated
      functions respectively from the DLPFC in patients with schizophrenia using these
      paradigms, compared to healthy controls. Given that these activities contribute
      to cognitive functions, the relationship between the TMS-evoked potential (TEP)
      modulations by SICI/ICF and cognitive/clinical measures were explored. Compared
      to controls, patients showed reduced inhibition in P60 (t22 = -4.961, p < 0.0001)
      by SICI and reduced facilitation in P60 (t22 = 5.174, p < 0.0001) and N100 (t22 =
      3.273, p = 0.003) by ICF. In patients, the modulation of P60 by SICI was
      correlated with the longest span of the Letter-Number Span Test (r = -0.775, p =
      0.003), while the modulation of N100 by ICF was correlated with the total score
      of the Positive and Negative. Syndrome Scale (r = 0.817, p = 0.002). These
      findings may represent the pathophysiology, which may be associated with
      prefrontal GABAA and glutamatergic dysfunctions, in the expression of symptoms of
      schizophrenia.

PMID- 29213091
TI  - Nitric oxide mediates apoptosis and mitochondrial dysfunction and plays a role in
      growth hormone deficiency by nivalenol in GH3 cells.
AB  - Nivalenol (NIV), a type B trichothecenes commonly found in cereal crops, can
      cause growth impairment in animals. However, limited information about its
      mechanisms is available. Trichothecenes have been characterized as an inhibitor
      of protein synthesis and induce apoptosis in cells. Oxidative stress is
      considered an underlying mechanism. However, whether NIV can induce oxidative
      stress and apoptosis in rat pituitary cells line GH3 is unclear. The present
      study showed that NIV significantly reduced the viability of cells and caused
      oxidative stress in GH3 cells. Further experiments showed that nitric oxide (NO),
      but not ROS, mediated NIV-induced oxidative stress. Additionally, NIV induced
      caspase-dependent apoptosis, decrease in mitochondrial membrane potential and
      mitochondrial ultrastructural changes. However, NIV-induced caspase activation,
      mitochondrial damage and apoptosis were partially alleviated by Z-VAD-FMK or NO
      scavenger hemoglobin. Finally, NIV changed the expression of growth-associated
      genes and pro-inflammatory cytokines. NIV also reduced the GH secretion in GH3
      cells, which was reversed by hemoglobin. Taken together, these results suggested
      that NIV induced apoptosis in caspase-dependent mitochondrial pathway in GH3
      cells, which might be an underlying mechanism of NIV-induced GH deficiency.
      Importantly, NO played a critical role in the induction of oxidative stress,
      apoptosis and GH deficiency in NIV-treated GH3 cells.

PMID- 29213093
TI  - Modeling pollen-mediated gene flow from glyphosate-resistant to -susceptible
      giant ragweed (Ambrosia trifida L.) under field conditions.
AB  - A field experiment was conducted to quantify pollen mediated gene flow (PMGF)
      from glyphosate-resistant (GR) to glyphosate-susceptible (GS) giant ragweed under
      simulated field conditions using glyphosate resistance as a selective marker.
      Field experiments were conducted in a concentric design with the GR giant ragweed
      pollen source planted in the center and GS giant ragweed pollen receptors
      surrounding the center in eight directional blocks at specified distances
      (between 0.1 and 35 m in cardinal and ordinal directions; and additional 50 m for
      ordinal directions). Seeds of GS giant ragweed were harvested from the pollen
      receptor blocks and a total of 100,938 giant ragweed plants were screened with
      glyphosate applied at 2,520 g ae ha-1 and 16,813 plants confirmed resistant. The
      frequency of PMGF was fit to a double exponential decay model selected by
      information-theoretic criteria. The highest frequency of gene flow (0.43 to 0.60)
      was observed at <=0.5 m from the pollen source and reduced rapidly with
      increasing distances; however, gene flow (0.03 to 0.04) was detected up to 50 m.
      The correlation between PMGF and wind parameters was inconsistent in magnitude,
      direction, and years.

PMID- 29213092
TI  - Developmental nonlinearity drives phenotypic robustness.
AB  - Robustness to perturbation is a fundamental feature of complex organisms.
      Mutations are the raw material for evolution, yet robustness to their effects is
      required for species survival. The mechanisms that produce robustness are poorly
      understood. Nonlinearities are a ubiquitous feature of development that may link
      variation in development to phenotypic robustness. Here, we manipulate the gene
      dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate
      development. We demonstrate that variation in Fgf8 expression has a nonlinear
      relationship to phenotypic variation, predicting levels of robustness among
      genotypes. Differences in robustness are not due to gene expression variance or
      dysregulation, but emerge from the nonlinearity of the genotype-phenotype curve.
      In this instance, embedded features of development explain robustness
      differences. How such features vary in natural populations and relate to genetic
      variation are key questions for unraveling the origin and evolvability of this
      feature of organismal development.

PMID- 29213094
TI  - Sodium fluoride exposure exerts toxic effects on porcine oocyte maturation.
AB  - Excessive long-term fluoride intake is associated with several health problems,
      including infertility. However, limited information is available on the toxic
      effects of fluoride exposure on the female reproductive system, especially oocyte
      maturation. In this study, we investigated the toxic effect of sodium fluoride
      (NaF) exposure on porcine oocyte maturation and its possible underlying
      mechanisms. Our results showed that NaF exposure during porcine oocyte maturation
      inhibited cumulus cell expansion and impaired polar body extrusion. Cell cycle
      analysis showed that NaF exposure blocked meiotic resumption, disturbed spindle
      dynamics, disrupted chromosome separation, and increased aneuploidy in porcine
      oocytes. Moreover, NaF exposure disturbed mitochondrial function, triggered DNA
      damage response, and induced early apoptosis in porcine oocytes. NaF exposure
      also induced oxidative stress, decreased GSH level, and increased cathepsin B
      activity in and impaired the further development potential of porcine oocytes, as
      indicated by a decrease in blastocyst formation rate, increase in apoptosis, and
      inhibition of cell proliferation. Together, these results indicate that NaF
      exposure impairs the maturation capacity of porcine oocytes by inhibiting cumulus
      cell expansion, disturbing cytoskeletal dynamics, and blocking nuclear and
      cytoplasmic maturation, thus decreasing the quality and affecting the subsequent
      embryonic development potential of porcine oocytes.

PMID- 29213095
TI  - Evolution of Energy Related Metabolites in Plasma from Newborns with Hypoxic
      Ischemic Encephalopathy during Hypothermia Treatment.
AB  - Therapeutic hypothermia (TH) initiated within 6 h from birth is the most
      effective therapeutic approach for moderate to severe hypoxic-ischemic
      encephalopathy (HIE). However, underlying mechanisms and effects on the human
      metabolism are not yet fully understood. This work aims at studying the evolution
      of several energy related key metabolites in newborns with HIE undergoing TH
      employing gas chromatography - mass spectrometry. The method was validated
      following stringent FDA requirements and applied to 194 samples from a subgroup
      of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP)
      for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle
      metabolites at different sampling time points. The analysis of plasma samples
      from newborns with HIE revealed a decrease of lactate, pyruvate and beta
      hydroxybutyrate concentrations, whereas rising malate concentrations were
      observed. In healthy control newborns (N = 19) significantly lower levels of
      pyruvate and lactate were found in comparison to age-matched newborns with HIE
      undergoing TH, whereas acetoacetate and beta-hydroxybutyrate levels were clearly
      increased. Access to a validated analytical method and a controlled cohort of
      newborns with HIE undergoing hypothermia treatment for the first time allowed the
      in-depth study of the evolution of key metabolites of metabolic junctions in this
      special population.

PMID- 29213096
TI  - Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and
      Amyloid-beta Pathologies in 3xTg Mice.
AB  - Amyloid-beta (Abeta) and tau pathologies are intertwined in Alzheimer's disease,
      and various immunotherapies targeting these hallmarks are in clinical trials. To
      determine if tau pathology influences Abeta burden and to assess prophylactic
      benefits, 3xTg and wild-type mice received tau immunization from 2-6 months of
      age. The mice developed a high IgG titer that was maintained at 22 months of age.
      Pronounced tau and Abeta pathologies were primarily detected in the subiculum/CA1
      region, which was therefore the focus of analysis. The therapy reduced
      histopathological tau aggregates by 70-74% overall (68% in males and 78-86% in
      females), compared to 3xTg controls. Likewise, western blot analysis revealed a
      41% clearance of soluble tau (38-76% in males and 48% in females) and 42-47%
      clearance of insoluble tau (47-58% in males and 49% in females) in the immunized
      mice. Furthermore, Abeta burden was reduced by 84% overall (61% in males and 97%
      in females). These benefits were associated with reductions in microgliosis and
      microhemorrhages. In summary, prophylactic tau immunization not only prevents tau
      pathology but also Abeta deposition and related pathologies in a sustained
      manner, indicating that tau pathology can promote Abeta deposition, and that a
      short immunization regimen can have a long-lasting beneficial effect.

PMID- 29213098
TI  - Bias induced ferromagnetism and half-metallicity in graphene nano-ribbons.
AB  - Towards spin selective electronics made of three coordinated carbon atoms, here
      we computationally propose robust and reversibly bias driven evolution of
      pristine undoped graphene nano-ribbons(GNR) into ferromagnetic-semiconductor,
      metal or a half metal, irrespective of their edge configurations. The evolution
      is a result of a rare ferromagnetic(FM) order emerging among nearest
      neighbouring(n-n) sites, in positively biased regions in their in-homogeneous
      bias unit-cells, in attempt to cooperatively minimise on-site Coulomb repulsion
      and kinetic energy, while maximising localization of electrons at the positively
      biased sites. The phenomenon appears to be a general property of in-homogeneously
      biased Coulomb correlated bipartite systems. Consequences are particularly rich
      in zigzag edged graphene nano-ribbons(ZGNR) due to the contest of bias driven n-n
      FM order and the inter-edge antiferromagnetic order inherent to ZGNRs, leading to
      systematic closing of gap for one of the spins, amounting to bias controlled
      unmissable opening of window for FM-semiconducting and half-metallic transport.

PMID- 29213097
TI  - Multiplexed computations in retinal ganglion cells of a single type.
AB  - In the early visual system, cells of the same type perform the same computation
      in different places of the visual field. How these cells code together a complex
      visual scene is unclear. A common assumption is that cells of a single-type
      extract a single-stimulus feature to form a feature map, but this has rarely been
      observed directly. Using large-scale recordings in the rat retina, we show that a
      homogeneous population of fast OFF ganglion cells simultaneously encodes two
      radically different features of a visual scene. Cells close to a moving object
      code quasilinearly for its position, while distant cells remain largely invariant
      to the object's position and, instead, respond nonlinearly to changes in the
      object's speed. We develop a quantitative model that accounts for this effect and
      identify a disinhibitory circuit that mediates it. Ganglion cells of a single
      type thus do not code for one, but two features simultaneously. This richer,
      flexible neural map might also be present in other sensory systems.

PMID- 29213099
TI  - Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic
      ductal adenocarcinoma.
AB  - Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC)
      support individualization of therapeutic strategies in this most aggressive
      disease. With the emergence of various novel therapeutic strategies and
      neoadjuvant approaches in this quickly deteriorating disease, robust approaches
      for fast evaluation of therapy response are urgently needed. To this aim, we
      designed a preclinical imaging-guided therapy trial where genetically engineered
      mice harboring endogenous aggressive PDAC were treated with the MEK targeting
      drug refametinib, which induces rapid and profound tumor regression in this model
      system. Multi-parametric non-invasive imaging was used for therapy response
      monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance
      Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours
      after treatment onset. Histopathological analyses showed increased apoptosis and
      matrix remodeling at this time point. Our findings suggest the ADC parameter as
      an early predictor of therapy response in PDAC.

PMID- 29213100
TI  - Altered spontaneous calcium signaling of in situ chondrocytes in human
      osteoarthritic cartilage.
AB  - Intracellular calcium ([Ca2+]i) signaling is an essential universal secondary
      messenger in articular chondrocytes. However, little is known about its
      spatiotemporal features in the context of osteoarthritis (OA). Herein, by
      examining the cartilage samples collected from patients undergoing knee
      arthroscopic surgery, we investigated the spatiotemporal features of spontaneous
      [Ca2+]i signaling in in situ chondrocytes at different OA stages. Our data showed
      zonal dependent spontaneous [Ca2+]i signaling in healthy cartilage samples under
      4 mM calcium environment. This signal was significantly attenuated in healthy
      cartilage samples but increased in early-degenerated cartilage when cultured in 0
      mM calcium environment. No significant difference was found in [Ca2+]i intensity
      oscillation in chondrocytes located in middle zones among ICRS 1-3 samples under
      both 4 and 0 mM calcium environments. However, the correlation was found in deep
      zone chondrocytes incubated in 4 mM calcium environment. In addition, increased
      protein abundance of Cav3.3 T-type voltage dependent calcium channel and Nfatc2
      activity were observed in early-degenerated cartilage samples. The present study
      exhibited OA severity dependent spatiotemporal features of spontaneous [Ca2+]i
      oscillations of in situ chondrocytes, which might reflect the zonal specific role
      of chondrocytes during OA progression and provide new insight in articular
      cartilage degradation during OA progression.

PMID- 29213101
TI  - Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE.
AB  - Widespread antibiotic resistance, especially of Gram-negative bacteria, has
      become a severe concern for human health. Tripartite efflux pumps are one of the
      major contributors to resistance in Gram-negative pathogens, by efficiently
      expelling a broad spectrum of antibiotics from the organism. In Neisseria
      gonorrhoeae, one of the first bacteria for which pan-resistance has been
      reported, the most expressed efflux complex is MtrCDE. Here we present the
      electrophysiological characterisation of the outer membrane component MtrE and
      the membrane fusion protein MtrC, obtained by a combination of planar lipid
      bilayer recordings and in silico techniques. Our in vitro results show that MtrE
      can be regulated by periplasmic binding events and that the interaction between
      MtrE and MtrC is sufficient to stabilize this complex in an open state. In
      contrast to other efflux conduits, the open complex only displays a slight
      preference for cations. The maximum conductance we obtain in the in vitro
      recordings is comparable to that seen in our computational electrophysiology
      simulations conducted on the MtrE crystal structure, indicating that this state
      may reflect a physiologically relevant open conformation of MtrE. Our results
      suggest that the MtrC/E binding interface is an important modulator of MtrE
      function, which could potentially be targeted by new efflux inhibitors.

PMID- 29213102
TI  - E-cadherin dynamics is regulated by galectin-7 at epithelial cell surface.
AB  - Re-epithelialisation of wounded epidermis is ensured by collective cell migration
      of keratinocytes. Efficient collective migration requires the maintenance of
      intercellular adhesion, notably through adherens junctions, to favour cell
      communication, support tension forces and coordinated movement . Galectin-7, a
      soluble lectin expressed in stratified epithelia, has been previously implicated
      in cell migration and intercellular adhesion. Here, we revealed a new function of
      galectin-7 in the control of directionality and collective behaviour in migrating
      keratinocytes. Consistently, we identified galectin-7 as a direct partner of E
      cadherin, a key component of adherens junctions. Unexpectedly, this interaction
      does not require glycosylation motifs. Focusing on the underlying mechanisms, we
      showed that galectin-7 stabilizes E-cadherin at the plasma membrane, restraining
      its endocytosis. Interestingly, galectin-7 silencing decreases E-cadherin
      mediated intercellular adhesion. Consequently, this study not only identifies a
      new stabilizer of adherens junctions but also emphasises the importance of the
      interplay between E-cadherin turnover and intercellular adhesion strength.

PMID- 29213103
TI  - Heterogeneous responses of temperate-zone amphibian populations to climate change
      complicates conservation planning.
AB  - The pervasive and unabated nature of global amphibian declines suggests common
      demographic responses to a given driver, and quantification of major drivers and
      responses could inform broad-scale conservation actions. We explored the
      influence of climate on demographic parameters (i.e., changes in the
      probabilities of survival and recruitment) using 31 datasets from temperate zone
      amphibian populations (North America and Europe) with more than a decade of
      observations each. There was evidence for an influence of climate on population
      demographic rates, but the direction and magnitude of responses to climate
      drivers was highly variable among taxa and among populations within taxa. These
      results reveal that climate drivers interact with variation in life-history
      traits and population-specific attributes resulting in a diversity of responses.
      This heterogeneity complicates the identification of conservation 'rules of
      thumb' for these taxa, and supports the notion of local focus as the most
      effective approach to overcome global-scale conservation challenges.

PMID- 29213104
TI  - Musical Imagery Involves Wernicke's Area in Bilateral and Anti-Correlated Network
      Interactions in Musicians.
AB  - Musical imagery is the human experience of imagining music without actually
      hearing it. The neural basis of this mental ability is unclear, especially for
      musicians capable of engaging in accurate and vivid musical imagery. Here, we
      created a visualization of an 8-minute symphony as a silent movie and used it as
      real-time cue for musicians to continuously imagine the music for repeated and
      synchronized sessions during functional magnetic resonance imaging (fMRI). The
      activations and networks evoked by musical imagery were compared with those
      elicited by the subjects directly listening to the same music. Musical imagery
      and musical perception resulted in overlapping activations at the anterolateral
      belt and Wernicke's area, where the responses were correlated with the auditory
      features of the music. Whereas Wernicke's area interacted within the intrinsic
      auditory network during musical perception, it was involved in much more complex
      networks during musical imagery, showing positive correlations with the dorsal
      attention network and the motor-control network and negative correlations with
      the default-mode network. Our results highlight the important role of Wernicke's
      area in forming vivid musical imagery through bilateral and anti-correlated
      network interactions, challenging the conventional view of segregated and
      lateralized processing of music versus language.

PMID- 29213105
TI  - Preoperative prostate health index predicts poor pathologic outcomes of radical
      prostatectomy in patients with biopsy-detected low-risk patients prostate cancer:
      results from a Chinese prospective cohort.
AB  - OBJECTIVE: To determine the performance of the prostate health index (PHI) in
      predicting pathologic outcomes of radical prostatectomy (RP) in Chinese patients
      with low-risk prostate cancer (PCa). METHODS: Of all consecutive patients who
      underwent RP in one tertiary center from September 2013 to January 2017, we
      prospectively examined the data of 140 patients with low-risk PCa based on the
      Prostate Cancer Research International: Active Surveillance (PRIAS) criteria. All
      patients were eligible for active surveillance, but underwent RP. Clinical and
      pathological data were collected. Logistic regression was used to evaluate the
      associations between the PHI and outcome of RP. The area under the receiver
      operating curve (AUC) was used to evaluate the accuracy of different models.
      Decision curve analysis was used to evaluate the potential clinical usefulness of
      making model-based decisions. RESULTS: Only 44 (31.4%) patients were finally
      confirmed to have organ-confined Gleason <=6 PCa. A low PHI was significantly
      predictive of organ-confined Gleason <=6 PCa (p = 0.001), while tPSA and f/tPSA
      were not associated with final pathology. In the multivariate analyses, addition
      of the PHI significantly increased the predictive accuracy (AUC = 0.767, 95% Cl
      0.685-0.849, p < 0.001). CONCLUSION: The PRIAS criteria for active surveillance
      may not suitable for Chinese patients with PCa. Addition of the PHI to the PRIAS
      models improved the prognostic performance. If confirmed in future larger and
      multicenter studies, PHI may help us to identify patients eligible for AS in
      China.

PMID- 29213106
TI  - All-optical control of light on a graphene-on-silicon nitride chip using thermo
      optic effect.
AB  - All-optical signal processing avoids the conversion between optical signals and
      electronic signals and thus has the potential to achieve a power efficient
      photonic system. Micro-scale all-optical devices for light manipulation are the
      key components in the all-optical signal processing and have been built on the
      semiconductor platforms (e.g., silicon and III-V semiconductors). However, the
      two-photon absorption (TPA) effect and the free-carrier absorption (FCA) effect
      in these platforms deteriorate the power handling and limit the capability to
      realize complex functions. Instead, silicon nitride (Si3N4) provides a
      possibility to realize all-optical large-scale integrated circuits due to its
      insulator nature without TPA and FCA. In this work, we investigate the physical
      dynamics of all-optical control on a graphene-on-Si3N4 chip based on thermo-optic
      effect. In the experimental demonstration, a switching response time constant of
      253.0 ns at a switching energy of ~50 nJ is obtained with a device dimension of
      60 MUm * 60 MUm, corresponding to a figure of merit (FOM) of 3.0 nJ mm. Detailed
      coupled-mode theory based analysis on the thermo-optic effect of the device has
      been performed.

PMID- 29213107
TI  - Brain-to-Brain Synchrony during Naturalistic Social Interactions.
AB  - The evolution of humans as a highly social species tuned the brain to the social
      world; yet the mechanisms by which humans coordinate their brain response online
      during social interactions remain unclear. Using hyperscanning EEG recordings, we
      measured brain-to-brain synchrony in 104 adults during a male-female naturalistic
      social interaction, comparing romantic couples and strangers. Neural synchrony
      was found for couples, but not for strangers, localized to temporal-parietal
      structures and expressed in gamma rhythms. Brain coordination was not found
      during a three-minute rest, pinpointing neural synchrony to social interactions
      among affiliative partners. Brain-to-brain synchrony was linked with behavioral
      synchrony. Among couples, neural synchrony was anchored in moments of social gaze
      and positive affect, whereas among strangers, longer durations of social gaze and
      positive affect correlated with greater neural synchrony. Brain-to-brain
      synchrony was unrelated to episodes of speech/no-speech or general content of
      conversation. Our findings link brain-to-brain synchrony to the degree of social
      connectedness among interacting partners, ground neural synchrony in key
      nonverbal social behaviors, and highlight the role of human attachment in
      providing a template for two-brain coordination.

PMID- 29213108
TI  - The potential therapeutic effect of melatonin on human ovarian cancer by
      inhibition of invasion and migration of cancer stem cells.
AB  - There is an urgent need to identify targeting molecules to control invasion and
      metastasis in cancer patients. We first isolated cancer stem cells (CSCs) from
      SKOV3 ovarian cancer cells and then investigated the role of melatonin in
      invasiveness and migration of CSCs compared to SKOV3 cells. The proportion of
      CSCs in SKOV3 cells was as low as 1.28% with overexpression of both CD133 and
      CD44. The ability of spheroid formation along with SOX2 overexpression revealed a
      high self-renewal potential in isolated cells. Melatonin (3.4 mM) inhibited
      proliferation of CSCs by 23% which was confirmed by a marked decrease in protein
      expression of Ki67, as a proliferation marker. Applying luzindole, a melatonin
      receptor 1, 2 inhibitor, partially abolished anti-proliferative effect of
      melatonin. Melatonin also decreased Epithelial mesenchymal transition (EMT)
      related gene expressions including ZEB1, ZEB2, snail and vimentin with increase
      in E-cadherin as a negative EMT regulator. Incubation of CSCs with melatonin
      showed a marked decrease in matrix metalloproteinase 9 (MMP9) expression and
      activity. Melatonin also inhibited CSCs migration in a partially receptor
      dependent and PI3k and MAPK independent manner. Melatonin can be considered as an
      important adjuvant to control invasion and metastasis especially in patients with
      high melatonin receptor expression.

PMID- 29213109
TI  - Healthy food choices are happy food choices: Evidence from a real life sample
      using smartphone based assessments.
AB  - Research suggests that "healthy" food choices such as eating fruits and
      vegetables have not only physical but also mental health benefits and might be a
      long-term investment in future well-being. This view contrasts with the belief
      that high-caloric foods taste better, make us happy, and alleviate a negative
      mood. To provide a more comprehensive assessment of food choice and well-being,
      we investigated in-the-moment eating happiness by assessing complete, real life
      dietary behaviour across eight days using smartphone-based ecological momentary
      assessment. Three main findings emerged: First, of 14 different main food
      categories, vegetables consumption contributed the largest share to eating
      happiness measured across eight days. Second, sweets on average provided
      comparable induced eating happiness to "healthy" food choices such as fruits or
      vegetables. Third, dinner elicited comparable eating happiness to snacking. These
      findings are discussed within the "food as health" and "food as well-being"
      perspectives on eating behaviour.

PMID- 29213111
TI  - The tight-binding formulation of the Kronig-Penney model.
AB  - Electronic band structure calculations are frequently parametrized in tight
      binding form; the latter representation is then often used to study electron
      correlations. In this paper we provide a derivation of the tight-binding model
      that emerges from the exact solution of a particle bound in a periodic one
      dimensional array of square well potentials. We derive the dispersion for such a
      model, and show that an effective next-nearest-neighbour hopping parameter is
      required for an accurate description. An electron-hole asymmetry is prevalent
      except in the extreme tight-binding limit, and emerges through a "next-nearest
      neighbour" hopping term in the dispersion. We argue that this does not
      necessarily imply next-nearest-neighbour tunneling; this assertion is
      demonstrated by deriving the transition amplitudes for a two-state effective
      model that describes a double-well potential, which is a simplified precursor to
      the problem of a periodic array of potential wells. A next-nearest-neighbour
      tunneling parameter is required for an accurate description even though there are
      no such neighbours.

PMID- 29213110
TI  - The relationship between dlPFC activity during unpredictable threat and CO2
      induced panic symptoms.
AB  - Panic disorder is characterized by sudden, repeated, and unexpected attacks of
      intense fear and overwhelming anxiety about when another attack may strike.
      Patients with panic disorder and healthy individuals with a history of panic
      attacks show a hypersensitivity to unpredictable threats, suggesting a possible
      link between panic and sustained anxiety. The purpose of this study was to
      determine the degree to which induced symptoms of panic relate to fear and
      anxiety, as well as activity in the neural systems that mediate and regulate
      these affective states. Psychological and physiological symptoms of panic were
      assessed during an 8-min 7.5% CO2 challenge task. Psychological, physiological,
      and neural symptoms of fear and anxiety were measured during two sessions (one
      psychophysiology and one functional magnetic resonance imaging where subjects
      experienced several blocks of no threat (N), predictable shock (P), and
      unpredictable shock (U; NPU threat task). We used a principle component analysis
      to characterize panic susceptibility (PS), and found that PS significantly
      predicted dorsolateral prefrontal cortex (dlPFC) activity to the unpredictable
      cue during the NPU threat task. When examining the weighted beta coefficients
      from this analysis, we observed that self-reported fear/anxiety during the CO2
      challenge negatively loaded onto dlPFC activity during the NPU task. Consistent
      with this observation, dlPFC activity during the unpredictable cue was also
      negatively correlated with anxiety during the NPU sessions. Together, these
      results suggest that panic symptoms and anxiety are regulated by the same
      prefrontal cognitive control system.

PMID- 29213112
TI  - Nanometer collimation enhancement of ion beams using channeling effects in track
      etched mica capillaries.
AB  - Long channels with diameter of few tens of nanometer are produced by chemical
      track etching of swift heavy ion irradiated muscovite sheets. Such small
      apertures are most suitable e.g. as beam defining apertures for focusing systems
      in ion beam facilities enabling beam diameters down to a few nanometers. One of
      the most important parameters to consider is the interaction of the ion beam with
      the walls of the aperture. We report angle-resolved transmission and energy-loss
      measurements of MeV ion beams through ion-track-etched capillaries with very high
      aspect ratio of about 60. For all ion energies, the angle-resolved transmission
      curves measured through the channels show a significant enhancement with respect
      to the expected pure geometrical considerations. This broadening of the
      acceptance angle increases further when the kinetic energy is reduced. This
      effect is ascribed to low-angle scattering of the ions at the surface of the
      muscovite capillary walls. These results are well described by simulations
      applying a similar approach as used for ion beam channeling in crystals.

PMID- 29213113
TI  - Intercalation events visualized in single microcrystals of graphite.
AB  - The electrochemical intercalation of layered materials, particularly graphite, is
      fundamental to the operation of rechargeable energy-storage devices such as the
      lithium-ion battery and the carbon-enhanced lead-acid battery. Intercalation is
      thought to proceed in discrete stages, where each stage represents a specific
      structure and stoichiometry of the intercalant relative to the host. However, the
      three-dimensional structures of the stages between unintercalated and fully
      intercalated are not known, and the dynamics of the transitions between stages
      are not understood. Using optical and scanning transmission electron microscopy,
      we video the intercalation of single microcrystals of graphite in concentrated
      sulfuric acid. Here we find that intercalation charge transfer proceeds through
      highly variable current pulses that, although directly associated with structural
      changes, do not match the expectations of the classical theories. Evidently
      random nanoscopic defects dominate the dynamics of intercalation.

PMID- 29213114
TI  - The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell
      function.
AB  - Chromatin remodelers have emerged as prominent regulators of epigenetic processes
      and potential drivers of various human pathologies. The multi-subunit chromatin
      remodeling SWI/SNF complex determines gene expression programs and, consequently,
      contributes to the differentiation, maturation and plasticity of neurons. Here,
      we investigate the elusive biological function of Bcl7a and Bcl7b, two newly
      identified subunits of the SWI/SNF complex that are highly expressed throughout
      the brain. We generated ubiquitous and neuron-specific Bcl7a and Bcl7b single and
      double knockout mice. We provide evidence that Bcl7b is dispensable for animal
      survival as well as behavioral plasticity. Conversely, ubiquitous Bcl7a knockout
      results in perinatal lethality, while genetic deletion of Bcl7a in postmitotic
      neurons elicits motor abnormalities and affects dendritic branching of Purkinje
      cells, with no obvious synergistic relationship with Bcl7b. Collectively, our
      findings reveal novel insights into the cellular processes linked to BCL7
      containing SWI/SNF complexes and their unrecognized roles in the brain.

PMID- 29213116
TI  - Author Correction: Control of in vivo ictogenesis via endogenous synaptic
      pathways.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29213115
TI  - Modulation of Immune Signaling and Metabolism Highlights Host and Fungal
      Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis.
AB  - Incidences of invasive pulmonary aspergillosis, an infection caused predominantly
      by Aspergillus fumigatus, have increased due to the growing number of
      immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in
      the host to facilitate invasive disease, the distinct mechanisms that govern the
      host-pathogen interaction remain enigmatic, particularly in the context of
      distinct immune modulating therapies. To gain insights into these mechanisms, RNA
      Seq technology was utilized to sequence RNA derived from lungs of 2 clinically
      relevant, but immunologically distinct murine models of IPA on days 2 and 3 post
      inoculation when infection is established and active disease present. Our
      findings identify notable differences in host gene expression between the
      chemotherapeutic and steroid models at the interface of immunity and metabolism.
      RT-qPCR verified model specific and nonspecific expression of 23 immune
      associated genes. Deep sequencing facilitated identification of highly expressed
      fungal genes. We utilized sequence similarity and gene expression to categorize
      the A. fumigatus putative in vivo secretome. RT-qPCR suggests model specific gene
      expression for nine putative fungal secreted proteins. Our analysis identifies
      contrasting responses by the host and fungus from day 2 to 3 between the two
      models. These differences may help tailor the identification, development, and
      deployment of host- and/or fungal-targeted therapeutics.

PMID- 29213117
TI  - Stimulus expectation alters decision criterion but not sensory signal in
      perceptual decision making.
AB  - Humans are more likely to report perceiving an expected than an unexpected
      stimulus. Influential theories have proposed that this bias arises from
      expectation altering the sensory signal. However, the effects of expectation can
      also be due to decisional criterion shifts independent of any sensory changes. In
      order to adjudicate between these two possibilities, we compared the behavioral
      effects of pre-stimulus cues (pre cues; can influence both sensory signal and
      decision processes) and post-stimulus cues (post cues; can only influence
      decision processes). Subjects judged the average orientation of a series of Gabor
      patches. Surprisingly, we found that post cues had a larger effect on response
      bias (criterion c) than pre cues. Further, pre and post cues did not differ in
      their effects on stimulus sensitivity (d') or the pattern of temporal or feature
      processing. Indeed, reverse correlation analyses showed no difference in the
      temporal or feature-based use of information between pre and post cues. Overall,
      post cues produced all of the behavioral modulations observed as a result of pre
      cues. These findings show that pre and post cues affect the decision through the
      same mechanisms and suggest that stimulus expectation alters the decision
      criterion but not the sensory signal itself.

PMID- 29213118
TI  - Vitamin K2 Prevents Lymphoma in Drosophila.
AB  - Previous studies have established the anticancer effect of vitamin K2 (VK2).
      However, its effect on lymphoma induced by UBIAD1/heix mutation in Drosophila
      remains unknown. Therefore, we aimed to develop an in vivo model of lymphoma for
      the precise characterization of lymphoma phenotypes. We also aimed to improve the
      understanding of the mechanisms that underlie the preventative effects of VK2 on
      lymphoma. Our results demonstrated that VK2 prevents lymphoma by acting as an
      electron carrier and by correcting the function and structure of mitochondria by
      inhibiting mitochondrial reactive oxygen species production mtROS. Our work
      identifies mitochondria as a key player in cancer therapy strategies.

PMID- 29213119
TI  - Electrostatic Map Of Proteasome alpha-Rings Encodes The Design of Allosteric
      Porphyrin-Based Inhibitors Able To Affect 20S Conformation By Cooperative
      Binding.
AB  - The importance of allosteric proteasome inhibition in the treatment of cancer is
      becoming increasingly evident. Motivated by this urgent therapeutic need, we have
      recently identified cationic porphyrins as a highly versatile class of molecules
      able to regulate proteasome activity by interfering with gating mechanisms. In
      the present study, the mapping of electrostatic contacts bridging the regulatory
      particles with the alpha-rings of the human 20S proteasome led us to the
      identification of (meso-tetrakis(4-N-methylphenyl pyridyl)-porphyrin (pTMPyPP4)
      as a novel non-competitive inhibitor of human 20S proteasome. pTMPyPP4 inhibition
      mechanism implies a positive cooperative binding to proteasome, which disappears
      when a permanently open proteasome mutant (alpha-3DeltaN) is used, supporting the
      hypothesis that the events associated with allosteric proteasome inhibition by
      pTMPyPP4 interfere with 20S gating and affect its "open-closed" equilibrium.
      Therefore, we propose that the spatial distribution of the negatively charged
      residues responsible for the interaction with regulatory particles at the alpha
      ring surface of human 20S may be exploited as a blueprint for the design of
      allosteric proteasome regulators.

PMID- 29213120
TI  - Stationary Rossby waves dominate subduction of anthropogenic carbon in the
      Southern Ocean.
AB  - The Southern Ocean has taken up more than 40% of the total anthropogenic carbon
      (Cant) stored in the oceans since the preindustrial era, mainly in subantarctic
      mode and intermediate waters (SAMW-AAIW). However, the physical mechanisms
      responsible for the transfer of Cant into the ocean interior remain poorly
      understood. Here, we use high resolution (1/10 degrees ) ocean simulations to
      investigate these mechanisms at the SAMW-AAIW subduction hotspots. Mesoscale
      Stationary Rossby Waves (SRWs), generated where the Antarctic Circumpolar Current
      interacts with topography, make the dominant contribution to the Cant transfer in
      SAMW-AAIW in the Indian and Pacific sectors (66% and 95% respectively). Eddy
      resolving simulations reproduce the observed Cant sequestration in these layers,
      while lower spatial resolution models, that do not reproduce SRWs, underestimate
      the inventory of Cant in these layers by 40% and overestimate the storage in
      denser layers. A key implication is that climate model simulations, that lack
      sufficient resolution to represent sequestration by SRWs, are therefore likely to
      overestimate the residence time of Cant in the ocean, with implications for
      simulated rates of climate change.

PMID- 29213122
TI  - Spondyloarthropathies: TNF inhibitors and structural damage in ankylosing
      spondylitis.

PMID- 29213121
TI  - The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian
      Population.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated
      with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and
      PCSK9 genes are known to cause FH. In this study, we analysed the genetic
      spectrum of the disease in subjects from the Iranian population with a clinical
      diagnosis of FH. Samples were collected from 16 children and family members from
      five different cities of Iran. Probands were screened for mutations in the LDLR,
      APOB, and PCSK9 genes using next generation sequencing, with results confirmed by
      Sanger sequencing. The likely pathology of identified variants was examined using
      in silico tools. Of the probands, 14 had a clinical diagnosis of homozygous FH
      and two of heterozygous FH. No mutations were found in either APOB or PCSK9, but
      nine probands were homozygous for seven different LDLR mutations, with
      p.(Trp577Arg) occurring in three and p.Val806Glyfs*11 occurring in two patients.
      Two mutations were novel: p.(Leu479Gln) and p.(Glu668*). Seven probands with a
      clinical diagnosis of FH were mutation negative. This pilot study, integrating
      clinical and molecular-based techniques, begins to elucidate the FH heterogeneity
      and the mutation spectrum in the Iranian population. Such information is
      important for future disease management and cost savings.

PMID- 29213123
TI  - Therapy: Rheumatic symptoms associated with immune checkpoint inhibition.

PMID- 29213125
TI  - The role of semaphorins in immune responses and autoimmune rheumatic diseases.
AB  - Semaphorins have a well-characterized role in guiding axon repulsion during
      development; however, the important contribution of these proteins in immunity is
      becoming increasingly clear. Immunoregulatory semaphorins, termed 'immune
      semaphorins', have roles in regulating immune cell activation, differentiation,
      mobility and migration. These proteins are also intimately associated with the
      pathogenesis of autoimmune diseases including rheumatoid arthritis (RA), systemic
      lupus erythematosus (SLE), systemic sclerosis (SSc) and anti-neutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This Review discusses
      the pathogenic functions of immune semaphorins, as well as the potential use of
      these molecules as diagnostic markers and therapeutic targets for the treatment
      of autoimmune diseases.

PMID- 29213126
TI  - Tuning Alginate Bioink Stiffness and Composition for Controlled Growth Factor
      Delivery and to Spatially Direct MSC Fate within Bioprinted Tissues.
AB  - Alginate is a commonly used bioink in 3D bioprinting. Matrix stiffness is a key
      determinant of mesenchymal stem cell (MSC) differentiation, suggesting that
      modulation of alginate bioink mechanical properties represents a promising
      strategy to spatially regulate MSC fate within bioprinted tissues. In this study,
      we define a printability window for alginate of differing molecular weight (MW)
      by systematically varying the ratio of alginate to ionic crosslinker within the
      bioink. We demonstrate that the MW of such alginate bioinks, as well as the
      choice of ionic crosslinker, can be tuned to control the mechanical properties
      (Young's Modulus, Degradation Rate) of 3D printed constructs. These same factors
      are also shown to influence growth factor release from the bioinks. We next
      explored if spatially modulating the stiffness of 3D bioprinted hydrogels could
      be used to direct MSC fate inside printed tissues. Using the same alginate and
      crosslinker, but varying the crosslinking ratio, it is possible to bioprint
      constructs with spatially varying mechanical microenvironments. Moreover, these
      spatially varying microenvironments were found to have a significant effect on
      the fate of MSCs within the alginate bioinks, with stiffer regions of the
      bioprinted construct preferentially supporting osteogenesis over adipogenesis.

PMID- 29213124
TI  - The RA-MAP Consortium: a working model for academia-industry collaboration.
AB  - Collaboration can be challenging; nevertheless, the emerging successes of large,
      multi-partner, multi-national cooperatives and research networks in the
      biomedical sector have sustained the appetite of academics and industry partners
      for developing and fostering new research consortia. This model has percolated
      down to national funding agencies across the globe, leading to funding for
      projects that aim to realise the true potential of genomic medicine in the 21st
      century and to reap the rewards of 'big data'. In this Perspectives article, the
      experiences of the RA-MAP consortium, a group of more than 140 individuals
      affiliated with 21 academic and industry organizations that are focused on making
      genomic medicine in rheumatoid arthritis a reality are described. The challenges
      of multi-partner collaboration in the UK are highlighted and wide-ranging
      solutions are offered that might benefit large research consortia around the
      world.

PMID- 29213127
TI  - Multivalent Fcgamma-receptor engagement by a hexameric Fc-fusion protein triggers
      Fcgamma-receptor internalisation and modulation of Fcgamma-receptor functions.
AB  - Engagement of Fcgamma-receptors triggers a range of downstream signalling events
      resulting in a diverse array of immune functions. As a result, blockade of Fc
      mediated function is an important strategy for the control of several autoimmune
      and inflammatory conditions. We have generated a hexameric-Fc fusion protein
      (hexameric-Fc) and tested the consequences of multi-valent Fcgamma-receptor
      engagement in in vitro and in vivo systems. In vitro engagement of hexameric-Fc
      with FcgammaRs showed complex binding interactions that altered with receptor
      density and triggered the internalisation and degradation of Fcgamma-receptors.
      This caused a disruption of Fc-binding and phagocytosis. In vivo, in a mouse ITP
      model we observed a short half-life of hexameric-Fc but were nevertheless able to
      observe inhibition of platelet phagocytosis several days after hexameric-Fc
      dosing. In cynomolgus monkeys, we again observed a short half-life, but were able
      to demonstrate effective FcgammaR blockade. These findings demonstrate the
      ability of multi-valent Fc-based therapeutics to interfere with FcgammaR function
      and a potential mechanism through which they could have a sustained effect; the
      internalisation and degradation of FcgammaRs.

PMID- 29213128
TI  - Complement 5a Receptor deficiency does not influence adverse cardiac remodeling
      after pressure-overload in mice.
AB  - Hypertension is one of the most common risk factors for the development heart
      failure in the general population. Inflammation plays a central role in this
      adverse remodeling and eventually to the development of heart failure.
      Circulating levels of Complement factor 5a (C5a) are increased in hypertensive
      patients and the C5a receptor is associated with the presence of cardiac fibrosis
      and inflammation in an experimental hypertension model. To test if C5aR is
      involved in adverse cardiac remodeling following pressure-overload, we induced
      transverse aortic constriction (TAC) in wildtype and C5a receptor deficient mice
      (C5aR-/-). Six weeks after TAC, C5aR-/- animals showed a similar degree of
      cardiac hypertrophy and decrease in cardiac function as wild type mice (End
      Systolic Volume; 50.30+/-5.32 ul vs. 55.81+/-8.16 ul). In addition, other
      features of adverse cardiac remodeling like cardiomyocyte cell size (WGA
      staining), fibrosis (picrosirius red staining) or collagen degradation (matrix
      metalloproteinase activity assay) did not differ either. In conclusion, full body
      C5aR deficiency does not affect adverse cardiac remodeling after pressure
      overload. However, our finding are in contrast with C5a inhibition studies. Our
      observations do present the role of C5a-C5aR in adverse cardiac remodeling and
      heart failure as controversial at the least.

PMID- 29213129
TI  - Deep tissue analysis of distal aqueous drainage structures and contractile
      features.
AB  - Outflow resistance in the aqueous drainage tract distal to trabecular meshwork is
      potentially an important determinant of intraocular pressure and success of
      trabecular bypass glaucoma surgeries. It is unclear how distal resistance is
      modulated. We sought to establish: (a) multimodal 2-photon deep tissue imaging
      and 3-dimensional analysis of the distal aqueous drainage tract (DT) in
      transgenic mice in vivo and ex vivo; (b) criteria for distinguishing the DT from
      blood and lymphatic vessels; and (c) presence of a DT wall organization capable
      of contractility. DT lumen appeared as scleral collagen second harmonic
      generation signal voids that could be traced back to Schlemm's canal. DT
      endothelium was Prox1-positive, CD31-positive and LYVE-1-negative, bearing a
      different molecular signature from blood and true lymphatic vessels. DT walls
      showed prominent filamentous actin (F-actin) labeling reflecting cells in a
      contracted state. F-actin co-localized with mesenchymal smooth muscle epitopes of
      alpha-smooth muscle actin, caldesmon and calponin, which localized adjacent and
      external to the endothelium. Our findings support a DT wall organization
      resembling that of blood vessels. This reflects a capacity to contract and
      support dynamic alteration of DT caliber and resistance analogous to the role of
      blood vessel tone in regulating blood flow.

PMID- 29213130
TI  - Superconductivity in two-dimensional ferromagnetic MnB.
AB  - Using the universal structure predictor algorithm, we proposed that two
      dimensional MnB structures with p4mmm (alpha-MnB) and pmma (beta-MnB) symmetries
      could be synthesized. This finding was verified by calculating the dynamical
      stability, molecular dynamics, and mechanical properties. The alpha-MnB had an in
      plane stiffness Y x (=Y y ) around 100 N/m while the beta-Mn displayed an
      asymmetric mechanical stiffness of Y x  = 186 N/m and Y y  = 139 N/m. Both
      systems displayed a ferromagnetic ground state with metallic band structures. The
      calculated magnetic moments were 2.14 and 2.34 uB per Mn-B pair in the alpha-MnB
      and beta-MnB. Furthermore, we investigated the potential superconductivity. In
      the alpha-MnB, we found the unique feature of Kohn anomaly at q~2kF in the
      diagonal direction of the Brillouin zone. The beta-MnB phonon spectra showed a
      valley of degenerated localized softening vibration modes at the edge of the
      Brillouin zone. The ZA and LA phonon branches in this valley induced the largest
      contribution to electron-phonon coupling strength. The calculated total electron
      phonon coupling parameters were 1.20 and 0.89 in alpha-MnB and beta-MnB systems.
      Overall, we predict that the alpha-MnB and beta-MnB systems can display 2D
      ferromagnetic superconducting states with the estimated critical temperatures of
      Tc ~ 10-13 K.

PMID- 29213131
TI  - Phagosomal transport depends strongly on phagosome size.
AB  - Macrophages internalize pathogens for intracellular degradation. An important
      part of this process is the phagosomal transport from the cell periphery to the
      perinuclear region. Biochemical factors are known to influence the fate of
      phagosomes. Here, we show that the size of phagosomes also has a strong influence
      on their transport. We found that large phagosomes are transported persistently
      to the nucleus, whereas small phagosomes show strong bidirectional transport. We
      show that dynein motors play a larger role in the transport of large phagosomes,
      whereas actin filament-based motility plays a larger role in the transport of
      small phagosomes. Furthermore, we investigated the spatial distribution of
      dyneins and microtubules around phagosomes and hypothesize that dynein and
      microtubule density differences between the nucleus-facing side of phagosomes and
      the opposite side could explain part of the observed transport characteristics.
      Our findings suggest that a size-dependent cellular sorting mechanism might exist
      that supports macrophages in their immunological roles.

PMID- 29213133
TI  - Plasma metabolomic profile varies with glucocorticoid dose in patients with
      congenital adrenal hyperplasia.
AB  - Glucocorticoid replacement therapy is the mainstay of treatment for congenital
      adrenal hyperplasia (CAH) but has a narrow therapeutic index and dose
      optimisation is challenging. Metabolomic profiling was carried out on plasma
      samples from 117 adults with 21-hydroxylase deficiency receiving their usual
      glucocorticoid replacement therapy who were part of the CaHASE study. Samples
      were profiled by using hydrophilic interaction chromatography with high
      resolution mass spectrometry. The patients were also profiled using nine routine
      clinical measures. The data were modelled by using both multivariate and
      univariate statistics by using the clinical metadata to inform the choice of
      patient groupings. Comparison of 382 metabolites amongst groups receiving
      different glucocorticoid doses revealed a clear distinction between patients
      receiving <=5 mg (n = 64) and >5 mg (n = 53) daily prednisolone-equivalent doses.
      The 24 metabolites which were statistically significantly different between
      groups included free fatty acids, bile acids, and amino acid metabolites. Using 7
      metabolites improved the receiver operating characteristic with area under the
      curve for predicting glucocorticoid dose of >0.9 with FDR adjusted P values in
      the range 3.3 E-04 -1.9 E-10. A combination of seven plasma metabolite biomarkers
      readily discriminates supraphysiological glucocorticoid replacement doses in
      patients with CAH.

PMID- 29213132
TI  - Reducing biomass recalcitrance by heterologous expression of a bacterial
      peroxidase in tobacco (Nicotiana benthamiana).
AB  - Commercial scale production of biofuels from lignocellulosic feed stocks has been
      hampered by the resistance of plant cell walls to enzymatic conversion, primarily
      owing to lignin. This study investigated whether DypB, the lignin-degrading
      peroxidase from Rodococcus jostii, depolymerizes lignin and reduces recalcitrance
      in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the
      cytosol or the ER using ER-targeting and retention signal peptides. For each
      construct, five independent transgenic lines were characterized phenotypically
      and genotypically. Our findings reveal that expression of DypB in the cytosol and
      ER does not affect plant development. ER-targeting increased protein
      accumulation, and extracts from transgenic leaves showed higher activity on
      classic peroxidase substrates than the control. Intriguingly, in situ DypB
      activation and subsequent saccharification released nearly 200% more fermentable
      sugars from transgenic lines than controls, which were not explained by variation
      in initial structural and non-structural carbohydrates and lignin content.
      Pyrolysis-GC-MS analysis showed more reduction in the level of lignin associated
      pyrolysates in the transgenic lines than the control primarily when the enzyme is
      activated prior to pyrolysis, consistent with increased lignin degradation and
      improved saccharification. The findings reveal for the first time that
      accumulation and in situ activation of a peroxidase improves biomass
      digestibility.

PMID- 29213135
TI  - Neuropsychiatric disorders: Stressful depression.

PMID- 29213137
TI  - Decision making: Valuable choices.

PMID- 29213136
TI  - Neurodevelopmental disorders: Misreading social smells.

PMID- 29213134
TI  - Anticipated moments: temporal structure in attention.
AB  - We have come to recognize the brain as a predictive organ, anticipating
      attributes of the incoming sensory stimulation to guide perception and action in
      the service of adaptive behaviour. In the quest to understand the neural bases of
      the modulatory prospective signals that prioritize and select relevant events
      during perception, one fundamental dimension has until recently been largely
      overlooked: time. In this Review, we introduce the burgeoning field of temporal
      attention and illustrate how the brain makes use of various forms of temporal
      regularities in the environment to guide adaptive behaviour and influence neural
      processing.

PMID- 29213138
TI  - Sleep: I feel the need, the need for sleep.

PMID- 29213139
TI  - Neurodegenerative disease: Remodelling neurodegeneration.

PMID- 29213141
TI  - [Evaluation of the impact of sagittal spinal curvatures on musculoskeletal
      disorders in young people].
AB  - BACKGROUND: In Poland, about 85% of the population report low back pain (LBP)
      symptoms overall. Moreover, 70-80% of people aged below 20 have already
      experienced back pain. The primary cause of LBP is the loss of spinal lordosis,
      which initiates changes in geometry of the spine and has impact on limb
      arrangement. The aim of the study was to attempt to verify the relationship
      between the 2 main curvatures of the spine and its relation to symptoms in
      different parts of the musculoskeletal system, in a group of adults. It was
      assumed that hyperlordosis of the lumbar spine and misbalance of the thoraco
      lumbar junction are risk factors for LBP. MATERIAL AND METHODS: The study coverd
      231 first-year students, (aged 19-21) of the University of Economics in Katowice.
      There were 103 men aged 19.5+/-0.8 years and 128 women aged 19.6+/-0.8 years. The
      students completed the Nordic Musculoskeletal Questionnaire (NMQ): 7 days (NMQ7)
      and 6 months (NMQ6). A Rippstein's plurimeter, was used to measure the angles of
      thoracic kyphosis (KTH) and lumbar lordosis (KLL). Cut of points was set at 30+/
      5. RESULTS: The results indicate strong and very strong correlation (r = 0.6 and
      r = 0.8, p < 0.05) between the concave of the back and LBP, which may suggest the
      relationship between these symptoms and the increased lordosis. CONCLUSIONS:
      Postural defects in the sagittal plane may predict the occurrence of pain. The
      results of the study indicate a higher frequency of pain in people with a higher
      angle of lumbar lordosis. Med Pr 2018;69(1):29-36.

PMID- 29213142
TI  - The attitudes of IVF patients treated in the Czech Republic towards informing
      children born after gamete donation.
AB  - BACKGROUND: In recent decades gamete donation has received growing attention.
      Data from the Czech National Registry of Assisted Reproduction show that the
      number of cycles using donated oocytes has been increasing every year. According
      to Czech law, gamete donation is anonymous. Since 2011, some members of the Czech
      parliament have repeatedly made requests to revoke the anonymity but anonymity is
      one of the preconditions for such donation in this country. The aim of this study
      was to find out how the gamete recipients feel towards informing their child
      about the circumstances of their conception and their access to the identity of
      the donor. METHODS: A total of 195 recipients (122 women undergoing treatment -
      43 Czechs, 79 foreigners (Western Europe and the USA) and 73 male partners - 28
      Czechs, 45 foreigners) participated in this survey. The data were obtained by
      anonymous questionnaire. RESULTS: A significant difference between the attitude
      of the future Czech and foreign parents regarding disclosing the mode of
      conception was found (P = 0.003). The vast majority of Czechs were against
      disclosure. The foreign recipients were somewhat more divided. Regarding the
      donor's identity, there was no difference in atttitude between the groups.
      Recipients rarely consider that the knowledge of the donor's identity will be
      important for their child. The recipients overall, were convinced that the
      psychological aspects of parenting are far more important to the child than
      genetics, and see no reasons for disclosing the donor's identity. CONCLUSION:
      While the the foreign recipients were less adamant about non-disclosure, the
      overall finding was in accord with the current Czech law on anonymity and not in
      agreement with the proposed abolition. The recipient's attitudes towards
      disclosing were also culturally determined. The fact that some countries have
      revised their rules towards open idendity is not a rationale for such change in
      the Czech Republic.

PMID- 29213140
TI  - Effects of stress on the development and progression of cardiovascular disease.
AB  - Cardiovascular disease remains the leading cause of disease burden globally,
      which underlies the continuing need to identify new complementary targets for
      prevention. Over the past 5-10 years, the pooling of multiple data sets into
      'mega-studies' has accelerated progress in research on stress as a risk and
      prognostic factor for cardiovascular disease. Severe stressful experiences in
      childhood, such as physical abuse and household substance abuse, can damage
      health and increase the risk of multiple chronic conditions in adulthood.
      Compared with childhood stress and adulthood classic risk factors, such as
      smoking, high blood pressure, and high serum cholesterol levels, the harmful
      effects of stress in adulthood are generally less marked. However, adulthood
      stress has an important role as a disease trigger in individuals who already have
      a high atherosclerotic plaque burden, and as a determinant of prognosis and
      outcome in those with pre-existing cardiovascular or cerebrovascular disease. In
      real-life settings, mechanistic studies have corroborated earlier laboratory
      based observations on stress-related pathophysiological changes that underlie
      triggering, such as lowered arrhythmic threshold and increased sympathetic
      activation with related increases in blood pressure, as well as pro-inflammatory
      and procoagulant responses. In some clinical guidelines, stress is already
      acknowledged as a target for prevention for people at high overall risk of
      cardiovascular disease or with established cardiovascular disease. However, few
      scalable, evidence-based interventions are currently available.

PMID- 29213144
TI  - Magnetic particle tracking for nonspherical particles in a cylindrical fluidized
      bed.
AB  - In granular flow operations, often particles are nonspherical. This has inspired
      a vast amount of research in understanding the behavior of these particles.
      Various models are being developed to study the hydrodynamics involving
      nonspherical particles. Experiments however are often limited to obtain data on
      the translational motion only. This paper focusses on the unique capability of
      Magnetic Particle Tracking to track the orientation of a marker in a full 3-D
      cylindrical fluidized bed. Stainless steel particles with the same volume and
      different aspect ratios are fluidized at a range of superficial gas velocities.
      Spherical and rod-like particles show distinctly different fluidization behavior.
      Also, the distribution of angles for rod-like particles changes with position in
      the fluidized bed as well as with the superficial velocity. Magnetic Particle
      Tracking shows its unique capability to study both spatial distribution and
      orientation of the particles allowing more in-depth validation of Discrete
      Particle Models.

PMID- 29213143
TI  - Lactate as an early predictor of psychomotor development in neonates with
      asphyxia receiving therapeutic hypothermia.
AB  - AIMS: This prospective study aimed to evaluate the relationship between
      persistently elevated lactate values in the arterial blood of newborns with grade
      II and III hypoxic ischemic encephalopathy (treated with therapeutic hypothermia)
      and psychomotor development at 24 months. METHODS: 51 neonates of gestational age
      from 36 to 41 weeks receiving therapeutic hypothermia for moderate to severe
      hypoxic ischaemic encephalopathy had arterial blood lactate levels regularly
      analysed. At 24 months the infants' psychomotor development was evaluated and
      they were divided into two groups - those where the outcome was favourable (i.e.
      normal psychomotor development) and adverse (severe motor or sensory impairment
      or death). The lactate dynamics over time were retrospectively evaluated from the
      data collected, with the normal upper limit set at 4 mmol/L. RESULTS: Of the 51
      affected neonates, 7 died over the course of the study. 34 of the remaining 44
      infants demonstrated normal psychomotor findings at 2 years old, with adverse
      findings in 10 cases. Although both groups experienced significant reductions in
      lactate over time, there were statistically significant differences between them
      regarding currently measured lactate levels. CONCLUSION: Absolute lactate values
      and their development over time can be a used as an auxiliary factor in making
      early estimates of the long-term outcome for newborns with neonatal asphyxia
      being treated with therapeutic hypothermia.

PMID- 29213145
TI  - A New Derivatization Reagent for HPLC-MS Analysis of Biological Organic Acids.
AB  - Small molecules containing carboxylic acid functional groups are ubiquitous
      throughout biology, playing vital roles in biological chemistry ranging from
      energy metabolism to cellular signaling. This paper describes a new
      derivatization reagent, 4-bromo-N-methylbenzylamine, which was selected for its
      potential to derivatize mono-, di- and tri-carboxylic acids, such as the
      intermediates of the tricarboxylic acid (TCA) cycle. This derivatization
      procedure facilitated the use of positive electrospray ionization (ESI) tandem
      mass spectrometry (MS/MS) detection of derivatized species allowing for clear
      identification thanks to the easily recognizable isotope pattern of the
      incorporated bromine. A liquid chromatography (LC)-MS/MS method was developed
      which provided limits of detection between 0.2 and 44 MUg L-1 in under 6 min,
      depending on the analyte and total analysis time. This method was successfully
      applied in both in vitro and in vivo models.

PMID- 29213147
TI  - Alexa, Can I Trust You?
AB  - Security diagnostics expose vulnerabilities and privacy threats that exist in
      commercial Intelligent Virtual Assistants (IVA) - diagnostics offer the
      possibility of securer IVA ecosystems.

PMID- 29213146
TI  - The Physicochemical Characteristics of Prosthetic Materials and Their Influence
      on Their Clinical Properties.
AB  - The use of elastic materials favours degradation of their surface. The period of
      their clinical usefulness is then shortened, and their further utilisation in the
      oral cavity may have the reverse effect. The surface properties of such material
      as well as the influence of the humidity on their surface are very important as
      they determine the prosthetic materials behavior in the mouth. The surface of
      such material should be resistant to water. Inverse gas chromatography is an
      accurate, sensitive technique for studying surface properties. Thanks to using a
      unique equipment specially designed for IGC technique, Surface Energy Analyzer,
      it was possible to characterize the surface at 0 and 80% of humidity. Our results
      show that increased humidity does not affect surface properties of studied
      prosthetic materials. Their ability to dispersive and specific interactions
      change in very limited degree. IGC experiment was also applied for the estimation
      of Hansen solubility parameters that indicate ability of a material to
      dispersive, polar, and hydrogen-bonding interactions. Relation between the
      surface characteristics and practical use of soft lining materials with
      implications for their clinical usefulness is also discussed.

PMID- 29213148
TI  - Kinetics of vacancy annealing upon time-linear heating applied to dilatometry.
AB  - A kinetic model for the diffusion-controlled annealing of excess vacancies under
      the experimentally relevant, non-isothermal condition of time-linear heating is
      presented and applied to dilatometry. The evolution of the vacancy concentration
      with time is quantitatively analyzed, considering as ideal sinks either
      dislocations or grain boundaries of spherical- or cylindrical-shaped
      crystallites. The validity of the model is tested using dilatometry data that
      were obtained for ultrafine-grained Ni prepared by high-pressure torsion. The
      entire two-stage annealing curve of the dilatometric length change can be
      analyzed by combining the present kinetic model of vacancy annealing at grain
      boundaries with established non-isothermal kinetics of recrystallization.

PMID- 29213149
TI  - Effect of Rubber Polarity on Cluster Formation in Rubbers Cross-Linked with Diels
      Alder Chemistry.
AB  - Diels-Alder chemistry has been used for the thermoreversible cross-linking of
      furan-functionalized ethylene/propylene (EPM) and ethylene/vinyl acetate (EVM)
      rubbers. Both furan-functionalized elastomers were successfully cross-linked with
      bismaleimide to yield products with a similar cross-link density. NMR relaxometry
      and SAXS measurements both show that the apolar EPM-g-furan precursor contains
      phase-separated polar clusters and that cross-linking with polar bismaleimide
      occurs in these clusters. The heterogeneously cross-linked network of EPM-g-furan
      contrasts with the homogeneous network in the polar EVM-g-furan. The
      heterogeneous character of the cross-links in EPM-g-furan results in a relatively
      high Young's modulus, whereas the more uniform cross-linking in EVM-g-furan
      results in a higher tensile strength and elongation at break.

PMID- 29213150
TI  - Strategies To Increase the Thermal Stability of Truly Biomimetic Hydrogels:
      Combining Hydrophobicity and Directed Hydrogen Bonding.
AB  - Enhancing the thermal stability of proteins is an important task for protein
      engineering. There are several ways to increase the thermal stability of proteins
      in biology, such as greater hydrophobic interactions, increased helical content,
      decreased occurrence of thermolabile residues, or stable hydrogen bonds. Here, we
      describe a well-defined polymer based on beta-helical polyisocyanotripeptides
      (TriPIC) that uses biological approaches, including hydrogen bonding and
      hydrophobic interactions for its exceptional thermal stability in aqueous
      solutions. The multiple hydrogen bonding arrays along the polymer backbone shield
      the hydrophobic core from water. Variable temperature CD and FTIR studies
      indicate that, on heating, a better packed polymer conformation further stiffens
      the backbone. Driven by hydrophobic interactions, TriPIC solutions give fully
      reversible hydrogels that can withstand high temperatures (80  degrees C) for
      extended times. Cryo-scanning electron microscopy (cryo-SEM), small-angle X-ray
      scattering (SAXS), and thorough rheological analysis show that the hydrogel has a
      bundled architecture, which gives rise to strain stiffening effects on
      deformation of the gel, analogous to many biological hydrogels.

PMID- 29213151
TI  - Learning based particle filtering object tracking for visible-light systems.
AB  - We propose a novel object tracking framework based on online learning scheme that
      can work robustly in challenging scenarios. Firstly, a learning-based particle
      filter is proposed with color and edge-based features. We train a. support vector
      machine (SVM) classifier with object and background information and map the
      outputs into probabilities, then the weight of particles in a particle filter can
      be calculated by the probabilistic outputs to estimate the state of the object.
      Secondly, the tracking loop starts with Lucas-Kanade (LK) affine template
      matching and follows by learning-based particle filter tracking. Lucas-Kanade
      method estimates errors and updates object template in the positive samples
      dataset, and learning-based particle filter tracker will start if the LK tracker
      loses the object. Finally, SVM classifier evaluates every tracked appearance to
      update the training set or restart the tracking loop if necessary. Experimental
      results show that our method is robust to challenging light, scale and pose
      changing, and test on eButton image sequence also achieves satisfactory tracking
      performance.

PMID- 29213152
TI  - Serological and molecular analysis of parvovirus B19 infection in Mayan women
      with systemic lupus erythematosus in Mexico.
AB  - Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      that mainly affects women, characterized by the production of autoantibodies. Its
      causal agent is unknown, but the combination of environmental, hormonal and
      genetic factors may favor the development of the disease. Parvovirus B19 has been
      associated with the development of SLE, since it induces the production of anti
      single stranded DNA antibodies. It is unknown whether PV-B19 infection is an
      environmental factor that trigger or reactivate SLE in the Mexican Mayan
      population. Aim: A preliminary serological and molecular study of PV-B19
      infection in Mayan women with established SLE was done. Methods: IgG and IgM anti
      PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of
      Mayan origin. Viral DNA and viral load were analyzed by qPCR. Results:
      Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and
      11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the
      patients and 82.9% (29/35) of control subjects, but were significantly higher in
      patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66)
      of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls
      which were positive for IgM and IgG, was significantly higher in controls.
      Conclusion: The high prevalence of PV-B19 in Yucatan, and the presence of IgM,
      IgG, and viral load in Mayan women with established SLE suggest that PV-B19
      infection could be an environmental factor to trigger or reactivate SLE.

PMID- 29213153
TI  - Reference values of amino acids, acylcarnitines and succinylacetone by tandem
      mass spectrometry for use in newborn screening in southwest Colombia.
AB  - Introduction: Inborn errors of metabolism (IEM) represent an important public
      health problem due to current diagnosis and treatment limitations, poor life
      quality of affected patients, and consequent untimely child death. In contrast to
      classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous
      evaluation of multiple metabolites associated with IEM offering higher
      sensitivity, low false positive rates and high throughput. Aims: Determine
      concentration levels for amino acids and acylcarnitines in blood of newborns from
      Colombia, to establish reference values for further use in diagnosis of IEM.
      Methods: Implementation of a method to determine amino acids, acylcarnitines and
      succinylacetone in newborn dried blood spots using MS/MS, and its application in
      a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo
      cities is described. Results: fifty-seven analytes that allow the diagnosis of
      more than 40 different pathologies were tested. The method showed to be linear,
      precise and accurate. Healthy neonates 1-18 days of age were included, 523 from
      Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the
      concentration levels of amino acids and acylcarnitines were observed whereas no
      significant differences by gender were found. Conclusion: The study has
      contributed to reveal the usual concentration levels of amino acids,
      acylcarnitines and succinylacetone that could be used as reference for the
      establishment of a newborn metabolic screening program in Colombia.

PMID- 29213154
TI  - Noise level in a neonatal intensive care unit in Santa Marta - Colombia.
AB  - Introduction: The environment of neonatal intensive care units is influenced by
      numerous sources of noise emission, which contribute to raise the noise levels,
      and may cause hearing impairment and other physiological and psychological
      changes on the newborn, as well as problems with care staff. Objective: To
      evaluate the level and sources of noise in the neonatal intensive care unit.
      Methods: Sampled for 20 consecutive days every 60 seconds in A-weighting curves
      and fast mode with a Type I sound level meter. Recorded the average, maximum and
      minimum, and the 10th, 50th and 90th percentiles. The values are integrated into
      hours and work shift, and studied by analysis of variance. The sources were
      characterized in thirds of octaves. Results: The average level was 64.00 +/-3.62
      dB(A), with maximum of 76.04 +/-5.73 dB(A), minimum of 54.84 +/-2.61dB(A), and
      background noise of 57.95 +/-2.83 dB(A). We found four sources with levels
      between 16.8-63.3 dB(A). Statistical analysis showed significant differences
      between the hours and work shift, with higher values in the early hours of the
      day. Conclusion: The values presented exceed the standards suggested by several
      organizations. The sources identified and measured recorded high values in low
      frequencies.

PMID- 29213155
TI  - Frailty syndrome and socioeconomic and health characteristics among older adults.
AB  - Objective: To investigate the association of frailty syndrome with socioeconomic
      and health variables among older adults. Methods: This is a cross-sectional,
      observational and analytical household research conducted with a sample of 1,609
      urban elderly. We used: semi-structured questionnaire, scales (Katz, Lawton and
      shortened version of Geriatric Depression Scale) and Fragility Phenotype proposed
      by Fried. Descriptive analysis was performed along with a bivariate and
      multinomial logistic regression model (p <0.05). Results: The prevalence of pre
      frailty condition was 52.0% and the fragility corresponded to 13.6%. Pre-frailty
      and frailty associated factors were, respectively: age range between 70-79 years
      and >=80 years; one to four morbidities and five or more morbidities categories;
      functional disability for basic and instrumental activities of daily life and
      depression indicative; whilst lack of a companion or income and female gender
      were only associated to pre-frailty. Conclusion: The conditions of pre-frailty
      and frailty levels were elevated with negative effects on the health of the
      elderly.

PMID- 29213156
TI  - Gastroesophageal reflux disease in patients with long standing type 1 diabetes
      mellitus: utility of two self-report questionnaires in a multifactorial disease.
AB  - Background: Gastroesophageal pathologies are common and multifactorial in
      patients with type 1 diabetes (T1DM). The evaluation with endoscopy and 24 h pH
      esophageal monitoring is expensive and not always available in all medical
      centers, especially in developing countries so more cost-effective algorithms for
      diagnosis are required. Clinical questionnaires are easy to apply but its utility
      for gastroesophageal reflux disease screening in patients with long standing T1DM
      must be analyzed. Objective: To evaluate the utility of the FSSG and Carlsson
      Dent (CDQ) questionnaires to detect the frequency of gastroesophageal reflux
      disease in patients with T1DM. Methods: Analytic cross-sectional study, included
      54 randomly selected patients from the T1DM clinic in our hospital. Before their
      routine evaluation, were asked to answer FSSG and CDQ questionnaires, classifying
      them as positive with a score >8 or >4, respectively. we associated and compared
      the clinical and biochemical characteristics between patients with or without
      gastroesophageal reflux detected through questionnaires. Results: Median age was
      29 years (22-35), 67% were female (median of 16 years from diagnosis). In 39% of
      the patients FSSG was positive, CDQ was positive in 28%. A total of 71% of
      patients were taking medications to treat non-specific gastric symptoms. The
      concordance between questionnaires was 65% (p: <0.001). Those patients with
      tobacco consumption as well as those with poor glycemic control were more likely
      to score positive in either questionnaire. Conclusions: Patients T1DM had a high
      prevalence of gastroesophageal reflux disease. In those patients FSSG
      questionnaire detected a higher number of patients in comparison with CDQ.

PMID- 29213157
TI  - Immunotherapy and gene therapy as novel treatments for cancer.
AB  - The immune system interacts closely with tumors during the disease development
      and progression to metastasis. The complex communication between the immune
      system and the tumor cells can prevent or promote tumor growth. New therapeutic
      approaches harnessing protective immunological mechanisms have recently shown
      very promising results. This is performed by blocking inhibitory signals or by
      activating immunological effector cells directly. Immune checkpoint blockade with
      monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and
      PD-1 has emerged as a successful treatment approach for patients with advanced
      melanoma. Ipilimumab is an anti-CTLA-4 antibody which demonstrated good results
      when administered to patients with melanoma. Gene therapy has also shown
      promising results in clinical trials. Particularly, Herpes simplex virus (HSV)
      mediated delivery of the HSV thymidine kinase (TK) gene to tumor cells in
      combination with ganciclovir (GCV) may provide an effective suicide gene therapy
      for destruction of glioblastomas, prostate tumors and other neoplasias by
      recruiting tumor-infiltrating lymphocytes into the tumor. The development of new
      treatment strategies or combination of available innovative therapies to improve
      cell cytotoxic T lymphocytes trafficking into the tumor mass and the production
      of inhibitory molecules blocking tumor tissue immune-tolerance are crucial to
      improve the efficacy of cancer therapy.

PMID- 29213158
TI  - Living Alone among Older Persons in Uganda: Prevalence and Associated Factors.
AB  - This study aimed at investigating the prevalence and factors associated with
      living alone among older persons in Uganda. A secondary analysis of the 2010
      Uganda National Household Survey (UNHS) data was conducted. A complementary log
      log regression model was used to estimate the association between living alone
      and demographic, socio-economic and health factors. Nearly one out of ten (9%)
      older persons lived alone in Uganda. Living alone was associated with being
      divorced / separated (OR 18.5, 95% CI: 10.3-33.3), being widowed (OR 8.8, 95% CI:
      5.1-15.2), advanced age (OR 2.1, 95% CI: 1.4-3.2), residence in western region
      (OR 0.6, 95% CI: 0.3-0.93), poor wealth status (OR 0.3, 95% CI: 0.2-06),
      receiving remittances (OR 1.6, 95% CI: 1.1-2.3) and being disabled (OR 1.6, 95%
      CI: 1.2-2.1). Living alone among older persons did not vary by gender.

PMID- 29213159
TI  - Nexus Between Demographic Change and Elderly Care Need in the Gulf Cooperation
      Council (GCC) Countries: Some Policy Implications.
AB  - Population ageing is a phenomenon affecting the whole world. The countries that
      make up the Gulf Cooperation Council (GCC) are no exception but transitions in
      population ageing are still in the early stages of the process. With current
      demographic dividends experienced by the GCC and the rest of the Middle-East, the
      pace of population ageing will be faster than that experienced by many European
      countries. The purpose of this paper is to explore the population ageing
      experience of different GCC countries while situating this within a context of
      social policies that still at the very early stages of acknowledging such change.
      We utilise data from sources such as the United Nations and the World Bank,
      complemented by policy analysis of current age-related social security measures
      in the GCC. Given the importance of the family aged care system in the region, we
      consider the implications of changes in family structures, living conditions, and
      care needs for the elderly. The findings confirm the declining trend in fertility
      combined with increased life expectancy in all the six GCC countries. However,
      they highlight that social policy measures focused on the older generations and
      their care needs are still relatively at the early stages of each country's
      policy agenda. The implications of such changes are serious in term of both the
      demand for and supply of care. Policy-makers need to adapt cohesive social policy
      strategies that strengthen the complementing relationships between the state,
      family and wider community as stakeholders in the provision of aged care.

PMID- 29213160
TI  - Isotope effects in mechanistic studies of l-tyrosine halogen derivatives
      hydroxylation catalyzed by tyrosinase.
AB  - The kinetic (KIE) and solvent (SIE) isotope effect methods were used to
      investigate the mechanism of enzymatic hydroxylation of halogenated derivatives
      of l-tyrosine to l-DOPA catalyzed by the enzyme tyrosinase (EC 1.14.18.1). The
      values of deuterium KIE and SIE were obtained using the non-competitive method
      with spectrophotometric measurements. The Lineweaver-Burk plots were used for
      determination of the inhibition mode of 3'-iodo-l-tyrosine. Based upon kinetic
      effects values the mechanism of action of enzyme tyrosinase was proposed.

PMID- 29213162
TI  - About the Cover.

PMID- 29213161
TI  - Comparison of PIXE and XRF in the analysis of silver denarii of the early Piast.
AB  - The collection of denarii from the time of development of a Polish medieval state
      was studied using the proton induced X-ray emission spectroscopy. The major
      elements detected for these denarii are Ag and Cu, while minor elements such as
      Pb, Fe, Au, Bi, and Zn may also be present. The aim of the study was to cross
      compare the results with a previous micro-X-ray fluorescence data and to perform
      a better quantification of the denarii elemental composition, especially for
      trace elements, providing suggestions of the origin of alloy compounds.

PMID- 29213163
TI  - Four decades of the Sudanese Journal of Paediatrics and milstones.

PMID- 29213164
TI  - Towards safe and effective transition from adolescence to adult care.
AB  - Transitional care is an important step in patients' care. This article aims to
      give some guidance towards a safe and smooth transition from adolescence to adult
      care. It highlights the definition, elements, steps, effects and benefits of an
      effective transition system.

PMID- 29213165
TI  - Prevalence of Helicobacter Pylori among Sudanese children admitted to a
      specialized children hospital.
AB  - The infection by Helicobacter Pylori (HP), a gram-negative bacillus, is more
      prevalent in the developing countries, and more often among younger people
      reaching up to 10% of the population in comparison to only 0.5% in more developed
      world. Generally HP is asymptomatic in children. This study aimed to determining
      the prevalence of Hp among Sudanese children and to recognize associated
      epidemiological features. It was a prospective cross sectional study at Gaafar
      Ibn Aouf children hospital (GCH) in the period between December 2010 and May
      2011. GCH is the largest specialized referral hospital in Khartoum and in the
      Sudan. Those who were diagnosed before as Hp positive were excluded. Full
      history, Physical examination was performed. A blood sample was taken from every
      patient and serum was kept at -20 degrees C to be tested for Hp IgG antibodies
      through ELISA kit (Monobind; Inc., California, USA) as directed by the
      Manufacturer, and 20 U/mL for antibodies was considered significant and positive.
      Using SPSS Version 21, categorical variables were compared with Chi-square test
      where P < 0.05 was taken as statistically significant. This current study
      included 128/312 (40.1%) children admitted to the hospital who were +ve for HP
      (56.3% = male). The prevalence of HP is 56.3% among Sudanese children Prevalence
      of HP increased with age and was directly related to mother and father level of
      education, socioeconomic status and positive family history.

PMID- 29213167
TI  - Pain assessment and management: The knowledge, attitude and practice of Sudanese
      Paediatric Residents.
AB  - This was a prospective, descriptive, cross sectional study that was conducted in
      9 major paediatric hospitals accredited for training of residents in Sudan to
      assess the knowledge, attitude and practice of residents in paediatrics on issues
      related to pain assessment and pain management in children A semi-structured and
      validated questionnaire was distributed to 174 residents working in these
      hospitals. One hundred and twenty residents, out of 174, responded by filling the
      questionnaire, with a response rate of 68%. Seventy percent of them said they had
      never received any kind of training, education, or learning sessions in
      paediatric pain assessment and management during their training, 60% were not
      aware of any pain assessment scale/tool. One third of residents thought opioids
      are contraindicated for chronic pain relief in children, as dependence and/or
      addiction would occur after short use. While attitude towards importance of pain
      control in children was generally good among surveyed residents (75%), two thirds
      of them had never used topical anaesthetic cream/lotion, while 40% of them had
      never used non-nutritive sucking and/or sucrose in neonates. In addition, more
      than a third had rarely used lubricant gel for nasogastric tube insertion. In
      conclusion, Sudanese paediatric residents in training had poor knowledge and
      training in paediatric pain assessment and treatment, however, the majority of
      them recognized the importance of pain control in children.

PMID- 29213166
TI  - Precocious puberty: An experience from a major teaching hospital in Central Saudi
      Arabia.
AB  - Precocious puberty is a developmental process that gives rise to secondary sexual
      characteristics before the age of 8 years in girls and 9 years in boys. In
      general, precocious puberty can be classified as central or peripheral. This is a
      retrospective hospital-based study was conducted at King Khalid University
      Hospital (KKUH), Riyadh, Saudi Arabia, during the period January 1990 and
      December 2016. Data were abstracted from the medical records of patients
      diagnosed with precocious puberty, with special emphasis on age, sex, clinical
      characteristics, and relevant hormonal assay. A total of 62 patients were
      diagnosed with Precocious Puberty (PP); 43 had Central Precocious Puberty (CPP)
      while 19 had peripheral precocious puberty (PPP). The majority of girls with CPP
      (68%) had idiopathic PP, while pathological causes were found in (50%) of boys.
      The commonest cause of PPP was congenital adrenal hyperplasia (42%) and chronic
      hypothyroidism (26%). In conclusion, this study showed that precocious Puberty is
      a common endocrine problem in our center. The etiology of CPP was idiopathic in
      the majority of girls while it was caused by CNS pathology in most of the boys in
      this cohort. Peripheral precocious puberty is not that rare and mainly caused by
      congenital adrenal hyperplasia or hypothyroidism.

PMID- 29213168
TI  - Pituitary imaging in 129 children with growth hormone deficiency: A spectrum of
      findings.
AB  - Growth Hormone (GH) deficiency is the most common pituitary hormone deficiency in
      children. Magnetic Resonance Imaging (MRI) of the brain detects structural
      pituitary anomalies associated with GH deficiency. This retrospective hospital
      based study was conducted at King Khalid University hospital (KKUH), Riyadh,
      Saudi Arabia, during the period (January 1995-June 2016). The available
      radiological, clinical and laboratory records of all children with confirmed GH
      deficiency by dynamic testing who had MRI brain were reviewed. A total of 129
      patients were diagnosed with GH deficiency and had MRI brain performed. Isolated
      GH deficiency (IGHD) was diagnosed in 118 (91.5%) and multiple pituitary hormone
      deficiency (MPHD) in 11 (8.5%) patients. Most children with IGHD had normal MRI
      findings (n = 86/118), while 14/118 had hypoplasia of the anterior pituitary and
      11/118 had aplasia of the anterior pituitary. Most of the children with MPHD
      (6/11) showed anterior pituitary hypoplasia or (3/11) aplasia and only 2/11
      children with MPHD had normal MRI. In conclusion, our study showed a spectrum of
      MRI changes in children with GH deficiency.

PMID- 29213169
TI  - Clinical profile of neural tube defects in Sudanese children: Is malaria a risk
      factor?
AB  - Neural tube defects (NTDs) are one of the most common structural malformations in
      human kind. It is a public health problem with great impact on the child, parents
      and the community at large. The aim is to study the epidemiological profile and
      patterns of NTDs in under five-year of age Sudanese children who attended the
      neurosurgical clinic at the National Centre of Neurological Sciences (NCNS),
      Khartoum during the period from March 2014 to December 2014. This was a
      prospective cross-sectional study conducted at the neurosurgery clinic in NCNS,
      Khartoum. A pre-set structured questionnaire was the research tool. All children
      under five-year of age with NTDs, who attended the Neurosurgery clinic in NCNS
      during the period of the study, were recruited. The data were analyzed using
      statistical package of social sciences (SPSS). The sample size was 71. The
      majority of cases were less than 6 months of age (57.7%). The female to male
      ratio was (1.2:1). Spinal defects were noticed to be more common than cranial
      defects. The spina bifida was the commonest anomaly accounting for (73.2%),
      whereas, encephaloceles accounted for (26.8%). The lumbo-sacral region was the
      commonest site (34.6%). Hydrocephalus was the most commonly associated anomaly.
      NTDs were common in the young mother age group and consanguine parents. Although
      folic acid was taken by (69.0%) of the mothers, it was not on regular bases in
      the majority. Infection, particularly, malaria, during pregnancy was reported in
      25.4%. Anti-malaria Sulfadoxine/Pyremethamine (Fansidar(r)) used by most in our
      cohort is an anti-folate drug and could be implicated in the etiology.

PMID- 29213170
TI  - Prune belly syndrome: A report of 15 cases from Sudan.
AB  - Prune belly syndrome is a rare congenital malformation of unknown aetiology,
      composed of a triad of deficient abdominal wall muscle, cryptorchidism and
      urinary tract anomalies. The majority of patients have associated pulmonary,
      skeletal, cardiac, and gastrointestinal defects. This was a prospective, case
      finding study that was conducted in the main paediatric hospitals in Khartoum
      state, during the period December 2015 to September 2016. A total of 15 patients
      with prune belly syndrome were collected. Patients' characteristics were noted
      including socio-demographic data, laboratory and radiological investigations and
      any medical or surgical intervention. There were 12 males and 3 females with a
      male to female ratio of 4:1. Most of the patients (80%) had hydronephrosis and
      hydroureter. The study revealed that 60% of the patients had associated
      anomalies, there were 4 (26.6%) with cardiac defects, 3 (20%) with orthopaedic
      defects one patient with small bowel volvulus and one patient with cleft lip. 6
      (40%) patients received medical intervention and 8 (53%) patients underwent
      surgical procedures. At the last follow up visit, 2 (13.4%) patients had normal
      renal function tests, 8 (53.3%) ended with chronic kidney disease, and 5 died
      with a mortality rate of 33.3%. Prune belly syndrome is a rare entity with wide
      variability in severity and clinical manifestations. The mortality in prune belly
      syndrome remains high despite medical and surgical interventions.

PMID- 29213171
TI  - Congenital sideroblastic anemia of a Saudi child.
AB  - Sideroblastic anemia is a heterogeneous group of disorders characterized by the
      presence of ring sideroblasts in the bone marrow, and has congenital and acquired
      forms. Congenital sideroblastic anemia is a rare condition, which is mostly X
      linked, caused by mutations of delta-aminolevulinic acid synthase 2. We describe
      one case of congenital sideroblastic anemia, indicating an autosomal recessive
      inheritance, with its clinico-hematological profile. It is important to recognize
      this entity early in life as a significant percentage of cases respond to
      pyridoxine thus avoiding any long-term complications.

PMID- 29213172
TI  - Spontaneous splenic rupture in typhomalaria: A case report with review of
      literature.
AB  - Plasmodium vivax, which was previously considered 'benign', has come out with
      unusual severe symptoms. We, here present an unusual case of Plasmodium vivax
      malaria presenting with spontaneous splenic rupture with hemoperitoneum, renal
      and pulmonary dysfunction. Following conservative management, there was an
      uneventful recovery, and the patient was discharged in a good general condition.

PMID- 29213173
TI  - Spine pathology in a girl with upper limb pain: A co-incidence or a causal
      relationship?
AB  - A 10-year-old girl was admitted to the Emergency Department due to a history of
      intermittent pain located in the left radiocarpal joint for a month, as well as
      in the interphalangeal joints of the left hand without any additional symptoms.
      Clinical examination revealed mild sensory deficits and diminished muscle
      strength of the left upper limb without any other pathologic findings. A Magnetic
      Resonance Imaging scan of the brain and spinal cord was performed, which
      confirmed a diagnosis of thoracic syringomyelia. We briefly discuss specific
      traits and diagnostic challenges of this entity in childhood. Our case highlights
      the difficulty in efficiently correlating a pathologic imaging finding with
      clinical neurologic symptoms and signs, as well as the value of a thorough
      clinical neurological evaluation. Furthermore, a clear discrimination of a causal
      relationship against an incidental co-existence of a radiological finding and a
      specific symptom is not always possible.

PMID- 29213174
TI  - X-linked hypophosphatemic rickets (PHEX mutation): A case report and literature
      review.
AB  - Hypophosphatemic rickets is a rare form of rickets that affect children. The
      diagnosis requires high index of suspicion. We report a case of Hypophosphatemic
      rickets in 18-month-old Saudi boy presented with delayed walking and lower limb
      deformity. The diagnosis was confirmed by bone profile, radiological study and
      genetic testing, which reveled PHEX mutation. The patient was successfully
      treated by phosphate supplement.

PMID- 29213175
TI  - Cutaneous larva migrans in a child.

PMID- 29213176
TI  - Adapting Agricultural Water Use to Climate Change in a Post-Soviet Context:
      Challenges and Opportunities in Southeast Kazakhstan.
AB  - The convergence of climate change and post-Soviet socio-economic and
      institutional transformations has been underexplored so far, as have the
      consequences of such convergence on crop agriculture in Central Asia. This paper
      provides a place-based analysis of constraints and opportunities for adaptation
      to climate change, with a specific focus on water use, in two districts in
      southeast Kazakhstan. Data were collected by 2 multi-stakeholder participatory
      workshops, 21 semi-structured in-depth interviews, and secondary statistical
      data. The present-day agricultural system is characterised by enduring Soviet-era
      management structures, but without state inputs that previously sustained
      agricultural productivity. Low margins of profitability on many privatised farms
      mean that attempts to implement integrated water management have produced water
      users associations unable to maintain and upgrade a deteriorating irrigation
      infrastructure. Although actors engage in tactical adaptation measures, necessary
      structural adaptation of the irrigation system remains difficult without
      significant public or private investments. Market-based water management models
      have been translated ambiguously to this region, which fails to encourage
      efficient water use and hinders adaptation to water stress. In addition, a mutual
      interdependence of informal networks and formal institutions characterises both
      state governance and everyday life in Kazakhstan. Such interdependence
      simultaneously facilitates operational and tactical adaptation, but hinders
      structural adaptation, as informal networks exist as a parallel system that
      achieves substantive outcomes while perpetuating the inertia and incapacity of
      the state bureaucracy. This article has relevance for critical understanding of
      integrated water management in practice and adaptation to climate change in post
      Soviet institutional settings more broadly.

PMID- 29213177
TI  - New Interest in Wild Forest Products in Europe as an Expression of Biocultural
      Dynamics.
AB  - In Europe, interest in wild forest products is increasing. Such products may be
      interpreted in a biological sense as deriving from autonomously growing forest
      species or in a biocultural sense as reflecting dynamics in human living with
      biodiversity through re-wilding of earlier domesticated species. In this article
      I elaborate the idea that the new interests reflect biocultural dynamics. First,
      I identify these dynamics as involving both domestication and re-wilding and
      characterize these processes as involving biological, environmental, and cultural
      dimensions. Next, I present a comparative review of two approaches to re-wilding
      forest production in the Netherlands: meat production from new types of natural
      grazing systems, and food production from plants re-introduced to the wild. The
      first approach is based on the stimulation of naturally occurring ecological
      processes and the second on the stimulation of new forms of experiencing bio
      cultural heritage. The examples demonstrate that the new interests in wild forest
      products involve both a return to earlier stages of domestication in an
      ecological sense and a new phase of acculturation to evolving socio-cultural
      conditions.

PMID- 29213178
TI  - Hiding in the dark: Local ecological knowledge about slow loris in Sarawak sheds
      light on relationships between human populations and wild animals.
AB  - Local ecological knowledge (LEK) increases understanding of certain species and
      the threats they face, especially little-studied taxa for which data on
      distribution and conservation are often lacking. We conducted 111 semi-structured
      interviews in Sarawak, Malaysia, to collect local knowledge about the behavior
      and distribution of the Philippine slow loris (Nycticebus menagensis) from two
      ethnic groups, the Iban and the Penan. Our study revealed that male Penan
      respondents, generally hunters, who frequently go into the forest were better at
      identifying animals from pictures. Overall, the Penan have a more detailed
      knowledge of slow loris behaviors, habitat, and distribution than the Iban. The
      two ethnic groups have different attitudes towards slow loris as the Penan hunt,
      eat, or keep them as pets while the Iban consider them sacred and signifiers of
      good luck. We advocate the use of LEK for providing complementary information to
      scientific methods in the study of cryptic animals.

PMID- 29213179
TI  - On the role of body size, brain size, and eye size in visual acuity.
AB  - Abstract: The visual system is highly variable across species, and such
      variability is a key factor influencing animal behavior. Variation in the visual
      system, for instance, can influence the outcome of learning tasks when visual
      stimuli are used. We illustrate this issue in guppies (Poecilia reticulata)
      artificially selected for large and small relative brain size with pronounced
      behavioral differences in learning experiments and mate choice tests. We
      performed a study of the visual system by quantifying eye size and optomotor
      response of large-brained and small-brained guppies. This represents the first
      experimental test of the link between brain size evolution and visual acuity. We
      found that female guppies have larger eyes than male guppies, both in absolute
      terms and in relation to their body size. Likewise, individuals selected for
      larger brains had slightly larger eyes but not better visual acuity than small
      brained guppies. However, body size was positively associated with visual acuity.
      We discuss our findings in relation to previous macroevolutionary studies on the
      evolution of brain morphology, eye morphology, visual acuity, and ecological
      variables, while stressing the importance of accounting for sensory abilities in
      behavioral studies. Significance statement: Pre-existing perceptual biases can be
      keys for the development of specific behavioral patterns. Hence, potential
      differences in sensory systems need to be taken into account in the study of
      animal behavior. We highlight this necessity concentrating on the visual domain
      and using experimental data on brain size-selected guppies in which we assessed
      eye size and visual acuity. Behavioral differences between large-brained and
      small-brained guppies in learning and mate choice predominantly relied on tests
      using visual cues. Analyses of visual capabilities in this system are therefore
      necessary. Furthermore, this system offers the unprecedented opportunity to
      experimentally test the relationship between brain size, eye morphology, and
      visual capabilities. Our results show similar visual acuities between large
      brained and small-brained guppies. However, the differences observed in eye area
      between the sexes, together with the observed positive relationship between body
      size and visual acuity, highlight the need to incorporate perceptive differences
      in the study of animal behavior.

PMID- 29213180
TI  - Names and "Doing Gender": How Forenames and Surnames Contribute to Gender
      Identities, Difference, and Inequalities.
AB  - Names, as proper nouns, are clearly important for the identification of
      individuals in everyday life. In the present article, I argue that forenames and
      surnames need also to be recognized as "doing" words, important in the
      categorization of sex at birth and in the ongoing management of gender conduct
      appropriate to sex category. Using evidence on personal naming practices in the
      United States and United Kingdom, I examine what happens at crisis points of
      sexed and gendered naming in the life course (for example, at the birth of
      babies, at marriage, and during gender-identity transitions). I show how
      forenames and surnames help in the embodied doing of gender and, likewise, that
      bodies are key to gendered practices of forenaming and surnaming: we have
      "gendered embodied named identities." Whether normative and compliant, pragmatic,
      or creative and resistant, forenaming and surnaming practices are revealed as
      core to the production and reproduction of binary sex categories and to gendered
      identities, difference, hierarchies, and inequalities.

PMID- 29213181
TI  - Physiology limits commercially viable photoautotrophic production of microalgal
      biofuels.
AB  - Algal biofuels have been offered as an alternative to fossil fuels, based on
      claims that microalgae can provide a highly productive source of compounds as
      feedstocks for sustainable transport fuels. Life cycle analyses identify algal
      productivity as a critical factor affecting commercial and environmental
      viability. Here, we use mechanistic modelling of the biological processes driving
      microalgal growth to explore optimal production scenarios in an industrial
      setting, enabling us to quantify limits to algal biofuels potential. We
      demonstrate how physiological and operational trade-offs combine to restrict the
      potential for solar-powered algal-biodiesel production in open ponds to a ceiling
      of ca. 8000 L ha-1 year-1. For industrial-scale operations, practical
      considerations limit production to ca. 6000 L ha-1 year-1. According to published
      economic models and life cycle analyses, such production rates cannot support
      long-term viable commercialisation of solar-powered cultivation of natural
      microalgae strains exclusively as feedstock for biofuels. The commercial
      viability of microalgal biofuels depends critically upon limitations in
      microalgal physiology (primarily in rates of C-fixation); we discuss the scope
      for addressing this bottleneck concluding that even deployment of genetically
      modified microalgae with radically enhanced characteristics would leave a very
      significant logistical if not financial burden.

PMID- 29213182
TI  - Genetic engineering of medium-chain-length fatty acid synthesis in Dunaliella
      tertiolecta for improved biodiesel production.
AB  - Genetic engineering of microalgae to accumulate high levels of medium-chain
      length fatty acids (MCFAs) represents an attractive strategy to improve the
      quality of microalgae-based biodiesel, but it has thus far been least successful.
      We demonstrate that one limitation is the availability of fatty acyl-acyl carrier
      protein (ACP) substrate pool for acyl-ACP thioesterase (TE). A combinational
      expression platform that involved plant lauric acid-biased TE (C12TE) and MCFA
      specific ketoacyl-ACP synthase (KASIV) increased lauric acid (C12:0) and myristic
      acid (C14:0) accumulation by almost sevenfold and fourfold, respectively,
      compared with native strain. These findings suggest a platform for further
      investigation into the enlargement of MCFA acyl-ACP substrate pool as an approach
      to sustainably improve quality of microalgae-based biodiesel with regard to MCFA
      production.

PMID- 29213183
TI  - Screening of new British thraustochytrids isolates for docosahexaenoic acid (DHA)
      production.
AB  - Thraustochytrids isolated from hot tropical and sub-tropical waters have been
      well studied for DHA and biodiesel production in the last decades. However,
      little research has been performed on the oils of cold water thraustochytrids, in
      particular from the North Sea region. In this study, thraustochytrid strains from
      British waters showed high relative levels of omega-3 long-chain (>=C20)
      polyunsaturated fatty acids (LC-PUFA), including docosahexaenoic acid (DHA,
      22:6omega3). The relative levels of DHA (as % of total fatty acids, TFA) in the
      different British strains are hitherto amongst the highest recorded from any
      thraustochytrid screening study, with strain TL18 reaching up to 67% DHA in
      modified Glucose-Yeast Extract-Peptone (GYP) medium. At this screening stage, low
      final biomass and fatty acid yield were observed in modified GYP and MarChiquita
      Brain Heart Broth (MCBHB), while PUFA profiles (as % of PUFA) remained unaltered
      regardless of the culture medium used. Hence, optimizing the medium and culture
      conditions to improve growth and lipid content, without impacting the relative
      percentage of DHA, has the potential to increase the final DHA concentration.
      With this in mind, three strains were identified as promising organisms for the
      production of DHA. In the context of possible future industrial exploitation
      involving a winterization step, we investigated the recycling of the residual oil
      for biodiesel use. To do this, a mathematical model was used to assess the
      intrinsic properties of the by-product oil. The results showed the feasibility of
      producing primary DHA-rich oil, assuming optimized conditions, while using the by
      product oil for biodiesel use.

PMID- 29213184
TI  - A comparison of methods for the non-destructive fresh weight determination of
      filamentous algae for growth rate analysis and dry weight estimation.
AB  - The determination of rates of macroalgal growth and productivity via temporal
      fresh weight (FW) measurements is attractive, as it does not necessitate the
      sacrifice of biomass. However, there is no standardised method for FW analysis;
      this may lead to potential discrepancies when determining growth rates or
      productivity and make literature comparison problematic. This study
      systematically assessed a variety of lab-scale methods for macroalgal FW
      measurement for growth rate determination. Method efficacy was assessed over a 14
      day period as impact upon algal physiology, growth rate on basis of FW and dry
      weight (DW), nitrate removal, and maintenance of structural integrity. The choice
      of method is critical to both accuracy and inter-study comparability of the data
      generated. In this study, it was observed that the choice of protocol had an
      impact upon the DW yield (P values = 0.036-0.51). For instance, those involving
      regular mechanical pressing resulted in a >25% reduction in the final DW in two
      of the three species studied when compared to algae not subjected to any
      treatment. This study proposes a standardised FW determination method employing a
      reticulated spinner that is rapid, reliable, and non-destructive and provides an
      accurate growth estimation.

PMID- 29213185
TI  - Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima
      and Laminaria digitata-seasonal variation and impact of environmental factors.
AB  - Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the
      cell walls of brown algae. The bioactive properties of fucoidans attract
      increasing interest from the medico-pharmaceutical industries and may drive an
      increase in demand of brown algae biomass. In nature, the biochemical composition
      of brown algae displays a seasonal fluctuation driven by environmental factors
      and endogenous rhythms. To cultivate and harvest kelps with high yields of
      fucoidans, knowledge is needed on seasonal variation and impact of environmental
      conditions on the fucoidan content of brown algae. The relations between the
      fucoidan content and key environmental factors (irradiance, nutrient
      availability, salinity and exposure) were examined by sampling natural
      populations of the common North Atlantic kelps, Saccharina latissima and
      Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in
      the Kattegat. In addition, laboratory experiments were carried out isolating the
      effects of the single factors. The results demonstrated that (1) seasonal
      variation alters the fucoidan content by a factor of 2-2.6; (2) interspecific
      differences exist in the concentrations of crude fucoidan (% of dry matter): L.
      digitata (11%) > S. latissima (6%); and (3) the effects of single environmental
      factors were not consistent between species or between different conspecific
      populations. The ambiguous response to single environmental factors complicates
      prospective directions for manipulating an increased content of fucoidan in a
      cultivation scenario and emphasizes the need for knowledge on performance of
      local kelp ecotypes.

PMID- 29213186
TI  - Cyclic fractionation process for Saccharina latissima using aqueous chelator and
      ion exchange resin.
AB  - A new approach to process Saccharina latissima algal biomass was developed using
      sodium citrate and a polyvalent cation-specific resin to sequentially extract the
      alginate into several usable fractions. The fractionation was performed in a
      cyclic manner, utilizing a stepwise removal of the native polyvalent ions present
      in the algae to isolate fractions of alginate with different solubility in the
      presence of these ions. Sodium citrate was used in different concentrations in
      the extraction solution to remove polyvalent cations to adjust the alginate
      liberation while AMBERLITE IRC718 resin was added to further remove these ions
      and regenerate the extraction solution. Alginate was recovered by acid
      precipitation and analyzed for its uronic acid composition and molecular weight,
      and the carbohydrate compositions of the insoluble and soluble parts of the algal
      biomass residue were determined. Finally, the fractionation method was assessed
      with a life cycle analysis to determine the energy and water efficiency as well
      as the greenhouse gas emissions and the results were compared to conventional
      alkaline extraction. The results indicate that the energy and water use as well
      as the emissions are considerably lower for the cyclic extraction in comparison
      with the conventional methods.

PMID- 29213187
TI  - The role of the whitefly, Bemisia tabaci (Gennadius), and farmer practices in the
      spread of cassava brown streak ipomoviruses.
AB  - Cassava brown streak disease (CBSD) is arguably the most dangerous current threat
      to cassava, which is Africa's most important food security crop. CBSD is caused
      by two RNA viruses: Cassava brown streak virus (CBSV) and Ugandan cassava brown
      streak virus (UCBSV). The roles of the whitefly Bemisia tabaci (Gennadius) and
      farmer practices in the spread of CBSD were investigated in a set of field and
      laboratory experiments. The virus was acquired and transmitted by B. tabaci
      within a short time (5-10 min each for virus acquisition and inoculation), and
      was retained for up to 48 hr. Highest virus transmission (60%) was achieved using
      20-25 suspected viruliferous whiteflies per plant that were given acquisition and
      inoculation periods of 24 and 48 hr, respectively. Experiments mimicking the
      agronomic practices of cassava leaf picking or the use of contaminated tools for
      making cassava stem cuttings did not show the transmission of CBSV or UCBSV.
      Screenhouse and field experiments in Tanzania showed that the spread of CBSD next
      to spreader rows was high, and that the rate of spread decreased with increasing
      distance from the source of inoculum. The disease spread in the field up to a
      maximum of 17 m in a cropping season. These results collectively confirm that
      CBSV and UCBSV are transmitted by B. tabaci semipersistently, but for only short
      distances in the field. This implies that spread over longer distances is due to
      movements of infected stem cuttings used for planting material. These findings
      have important implications for developing appropriate management strategies for
      CBSD.

PMID- 29213188
TI  - A novel framework for intelligent surveillance system based on abnormal human
      activity detection in academic environments.
AB  - Abnormal activity detection plays a crucial role in surveillance applications,
      and a surveillance system that can perform robustly in an academic environment
      has become an urgent need. In this paper, we propose a novel framework for an
      automatic real-time video-based surveillance system which can simultaneously
      perform the tracking, semantic scene learning, and abnormality detection in an
      academic environment. To develop our system, we have divided the work into three
      phases: preprocessing phase, abnormal human activity detection phase, and content
      based image retrieval phase. For motion object detection, we used the temporal
      differencing algorithm and then located the motions region using the Gaussian
      function. Furthermore, the shape model based on OMEGA equation was used as a
      filter for the detected objects (i.e., human and non-human). For object
      activities analysis, we evaluated and analyzed the human activities of the
      detected objects. We classified the human activities into two groups: normal
      activities and abnormal activities based on the support vector machine. The
      machine then provides an automatic warning in case of abnormal human activities.
      It also embeds a method to retrieve the detected object from the database for
      object recognition and identification using content-based image retrieval.
      Finally, a software-based simulation using MATLAB was performed and the results
      of the conducted experiments showed an excellent surveillance system that can
      simultaneously perform the tracking, semantic scene learning, and abnormality
      detection in an academic environment with no human intervention.

PMID- 29213189
TI  - SpikingLab: modelling agents controlled by Spiking Neural Networks in Netlogo.
AB  - The scientific interest attracted by Spiking Neural Networks (SNN) has lead to
      the development of tools for the simulation and study of neuronal dynamics
      ranging from phenomenological models to the more sophisticated and biologically
      accurate Hodgkin-and-Huxley-based and multi-compartmental models. However,
      despite the multiple features offered by neural modelling tools, their
      integration with environments for the simulation of robots and agents can be
      challenging and time consuming. The implementation of artificial neural circuits
      to control robots generally involves the following tasks: (1) understanding the
      simulation tools, (2) creating the neural circuit in the neural simulator, (3)
      linking the simulated neural circuit with the environment of the agent and (4)
      programming the appropriate interface in the robot or agent to use the neural
      controller. The accomplishment of the above-mentioned tasks can be challenging,
      especially for undergraduate students or novice researchers. This paper presents
      an alternative tool which facilitates the simulation of simple SNN circuits using
      the multi-agent simulation and the programming environment Netlogo (educational
      software that simplifies the study and experimentation of complex systems). The
      engine proposed and implemented in Netlogo for the simulation of a functional
      model of SNN is a simplification of integrate and fire (I&F) models. The
      characteristics of the engine (including neuronal dynamics, STDP learning and
      synaptic delay) are demonstrated through the implementation of an agent
      representing an artificial insect controlled by a simple neural circuit. The
      setup of the experiment and its outcomes are described in this work.

PMID- 29213190
TI  - Smartphone-based imaging of the corneal endothelium at sub-cellular resolution.
AB  - This aim of this study was to test the feasibility of smartphone-based specular
      microscopy of the corneal endothelium at a sub-cellular resolution. Quantitative
      examination of endothelial cells is essential for evaluating corneal disease such
      as determining a diagnosis, monitoring progression and assessing treatment.
      Smartphone-based technology promises a new opportunity to develop affordable
      devices to foster quantitative examination of endothelial cells in rural and
      underserved areas. In our study, we incorporated an iPhone 6 and a slit lamp to
      demonstrate the feasibility of smartphone-based microscopy of the corneal
      endothelium at a sub-cellular resolution. The sub-cellular resolution images
      allowed quantitative calculation of the endothelial cell density. Comparative
      measurements revealed a normal endothelial cell density of 2978 cells/mm2 in the
      healthy cornea, and a significantly reduced cell density of 1466 cells/mm2 in the
      diseased cornea with Fuchs' dystrophy. Our ultimate goal is to develop a
      smartphone-based telemedicine device for low-cost examination of the corneal
      endothelium, which can benefit patients in rural areas and underdeveloped
      countries to reduce health care disparities.

PMID- 29213191
TI  - How mothers in poverty explain their use of corporal punishment: A qualitative
      study in Kampala, Uganda.
AB  - Corporal punishment in the early years is associated with anti-social behaviour
      and violence, but little is known about its social and cultural context in low
      income countries. This paper analyses how 12 deprived women in Kampala, Uganda,
      perceived corporal punishment, drawing on repeated semi-structured interviews.
      All thought it was sometimes necessary, for three main reasons. First, it was an
      important strategy to ensure good behaviour and maintain their and their child's,
      respectability, crucial to self-respect given severe poverty. Second, it was a
      means of establishing household routines and managing scarce resources. Third, it
      was a way to protect children from health risks. However, all mothers thought
      corporal punishment could be excessive, and most said it can be counter
      productive, making children 'stubborn'. There appeared to be considerable
      variation in their degree of harsh parenting and emotional support. These
      findings could inform culturally appropriate interventions to reduce violence
      against children.

PMID- 29213194
TI  - Bounded perturbation resilience of extragradient-type methods and their
      applications.
AB  - In this paper we study the bounded perturbation resilience of the extragradient
      and the subgradient extragradient methods for solving a variational inequality
      (VI) problem in real Hilbert spaces. This is an important property of algorithms
      which guarantees the convergence of the scheme under summable errors, meaning
      that an inexact version of the methods can also be considered. Moreover, once an
      algorithm is proved to be bounded perturbation resilience, superiorization can be
      used, and this allows flexibility in choosing the bounded perturbations in order
      to obtain a superior solution, as well explained in the paper. We also discuss
      some inertial extragradient methods. Under mild and standard assumptions of
      monotonicity and Lipschitz continuity of the VI's associated mapping, convergence
      of the perturbed extragradient and subgradient extragradient methods is proved.
      In addition we show that the perturbed algorithms converge at the rate of
      [Formula: see text]. Numerical illustrations are given to demonstrate the
      performances of the algorithms.

PMID- 29213193
TI  - Anti-Inflammatory Activity of Crude Venom Isolated from Parasitoid Wasp, Bracon
      hebetor Say.
AB  - Pest control in the agricultural fields, a major concern globally, is currently
      achieved through chemical or biological methods. Chemical methods, which leave
      toxic residue in the produce, are less preferred than biological methods. Venoms
      injected by stings of various wasps that kill the pest is considered as the
      examples of the biological method. Although several studies have investigated the
      biological control of pests through these venoms, very few studies have reported
      the effects of these venoms on mammalian cells. Bracon hebetor, an ectoparasitoid
      of the order Hymenoptera, is having a paramount importance in parasitizing
      various lepidopterous larvae including Plodia interpunctella also called as
      Indianmeal moth (IMM). Since it is biologically controlled by B. hebetor venom,
      therefore in our study, herein for the first time, we report the anti
      inflammatory activities of the venom from B. hebetor (BHV). We developed a septic
      shock mice model for in vivo anti-inflammatory studies and RAW 264.7 cells for in
      vitro studies. Our results clearly demonstrate that BHV can dose dependently
      abrogate the nitric oxide (NO) production and suppress the levels of
      proinflammatory mediators and cytokines without posing any cytotoxicity via the
      nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK)
      pathways.

PMID- 29213195
TI  - Bivariate tensor product [Formula: see text]-analogue of Kantorovich-type
      Bernstein-Stancu-Schurer operators.
AB  - In this paper, we construct a bivariate tensor product generalization of
      Kantorovich-type Bernstein-Stancu-Schurer operators based on the concept of
      [Formula: see text]-integers. We obtain moments and central moments of these
      operators, give the rate of convergence by using the complete modulus of
      continuity for the bivariate case and estimate a convergence theorem for the
      Lipschitz continuous functions. We also give some graphs and numerical examples
      to illustrate the convergence properties of these operators to certain functions.

PMID- 29213192
TI  - Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration.
AB  - Cutaneous wound healing is a complex multiple phase process, which overlaps each
      other, where several growth factors, cytokines, chemokines, and various cells
      interact in a well-orchestrated manner. However, an imbalance in any of these
      phases and factors may lead to disruption in harmony of normal wound healing
      process, resulting in transformation towards chronic nonhealing wounds and
      abnormal scar formation. Although various therapeutic interventions are available
      to treat chronic wounds, current wound-care has met with limited success.
      Progenitor stem cells possess potential therapeutic ability to overcome
      limitations of the present treatments as it offers accelerated wound repair with
      tissue regeneration. A substantial number of stem cell therapies for cutaneous
      wounds are currently under development as a result of encouraging preliminary
      findings in both preclinical and clinical studies. However, the mechanisms by
      which these stem cells contribute to the healing process have yet to be
      elucidated. In this review, we emphasize on the major treatment modalities
      currently available for the treatment of the wound, role of various interstitial
      stem cells and exogenous adult stem cells in cutaneous wound healing, and
      possible mechanisms involved in the healing process.

PMID- 29213196
TI  - Some further results on the stability of Ky Fan's points.
AB  - In this paper, some further results on the stability of Ky Fan's points are
      proposed by introducing a type of stronger perturbation of section mappings
      defined by a semi-metric called the maximum Hausdorff semi-metric, and the
      existence of the essential components of the set of Ky Fan's points to this
      perturbation is proved. As an application, the existence of the essential
      component of the Nash equilibrium is presented using the proposed method, and
      strong robustness to payoff function perturbation is achieved.

PMID- 29213197
TI  - The complete moment convergence for CNA random vectors in Hilbert spaces.
AB  - In this paper we establish the complete moment convergence for sequences of
      coordinatewise negatively associated random vectors in Hilbert spaces. The result
      extends the complete moment convergence in (Ko in J. Inequal. Appl. 2016:131,
      2016) to Hilbert spaces as well as generalizes the Baum-Katz type theorem in
      (Huan et al. in Acta Math. Hung. 144(1):132-149, 2014) to the complete moment
      convergence.

PMID- 29213198
TI  - A Mizuno-Todd-Ye predictor-corrector infeasible-interior-point method for
      symmetric optimization with the arc-search strategy.
AB  - In this paper, we propose a Mizuno-Todd-Ye predictor-corrector infeasible
      interior-point method for symmetric optimization using the arc-search strategy.
      The proposed algorithm searches for optimizers along the ellipses that
      approximate the central path and ensures that the duality gap and the
      infeasibility have the same rate of decline. By analyzing, we obtain the
      iteration complexity [Formula: see text] for the Nesterov-Todd direction, where r
      is the rank of the associated Euclidean Jordan algebra and epsilon is the
      required precision. To our knowledge, the obtained complexity bounds coincide
      with the currently best known theoretical complexity bounds for infeasible
      symmetric optimization.

PMID- 29213199
TI  - Oscillation and variation inequalities for the multilinear singular integrals
      related to Lipschitz functions.
AB  - The main purpose of this paper is to establish the weighted [Formula: see text]
      inequalities of the oscillation and variation operators for the multilinear
      Calderon-Zygmund singular integral with a Lipschitz function.

PMID- 29213200
TI  - Some limit theorems for ratios of order statistics from uniform random variables.
AB  - In this paper, we study the ratios of order statistics based on samples drawn
      from uniform distribution and establish some limit properties such as the almost
      sure central limit theorem, the large deviation principle, the Marcinkiewicz
      Zygmund law of large numbers and complete convergence.

PMID- 29213201
TI  - Eigenvalues of the resistance-distance matrix of complete multipartite graphs.
AB  - Let [Formula: see text] be a simple graph. The resistance distance between
      [Formula: see text], denoted by [Formula: see text], is defined as the net
      effective resistance between nodes i and j in the corresponding electrical
      network constructed from G by replacing each edge of G with a resistor of 1 Ohm.
      The resistance-distance matrix of G, denoted by [Formula: see text], is a
      [Formula: see text] matrix whose diagonal entries are 0 and for [Formula: see
      text], whose ij-entry is [Formula: see text]. In this paper, we determine the
      eigenvalues of the resistance-distance matrix of complete multipartite graphs.
      Also, we give some lower and upper bounds on the largest eigenvalue of the
      resistance-distance matrix of complete multipartite graphs. Moreover, we obtain a
      lower bound on the second largest eigenvalue of the resistance-distance matrix of
      complete multipartite graphs.

PMID- 29213202
TI  - Strong convergence of gradient projection method for generalized equilibrium
      problem in a Banach space.
AB  - In this paper, we propose and analyze a hybrid iterative method for finding a
      common element of the set of solutions of a generalized equilibrium problem, the
      set of solutions of a variational inequality problem, and the set of fixed points
      of a relatively nonexpansive mapping in a real Banach space. Further, we prove
      the strong convergence of the sequences generated by the iterative scheme.
      Finally, we derive some consequences from our main result. Our work is an
      improvement and extension of some previously known results recently obtained by
      many authors.

PMID- 29213203
TI  - On a boundary property of analytic functions.
AB  - Let f be an analytic function in the unit disc [Formula: see text] on the complex
      plane [Formula: see text]. This paper is devoted to obtaining the correspondence
      between [Formula: see text] and [Formula: see text] at the point w, [Formula: see
      text], such that [Formula: see text]. We present several applications of the main
      result. A part of them improve the previous results of this type.

PMID- 29213204
TI  - In vitro release of two anti-muscarinic drugs from soft contact lenses.
AB  - The purpose of this study was to investigate the release of the anti-myopia drugs
      atropine sulfate and pirenzepine dihydrochloride from commercially available soft
      contact lenses. Standard ultraviolet (UV) absorbance-concentration curves were
      generated for atropine and pirenzepine. Ten commercially available contact
      lenses, including four multifocal lenses, were loaded by soaking in atropine or
      pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL). The
      release of the drugs into phosphate-buffered saline was determined over the
      course of 24 hours at 34 degrees C using UV absorbance. Materials with surface
      charge released the greatest amount of atropine when loaded with either
      concentration when compared to the other lens types (p<0.05), releasing upward of
      1.026+/-0.035 mg/lens and 0.979+/-0.024 mg/lens from etafilcon A and ocufilcon A,
      respectively. There were no significant differences in the amount of atropine or
      pirenzepine released from the multifocal and non-multifocal lenses made from the
      same lens materials. Narafilcon A material demonstrated prolonged release of up
      to 8 hours when loaded with pirenzepine, although the overall dose delivered from
      the lens into the solution was among the lowest of the materials investigated.
      The rest of the lenses reached a plateau within 2 hours of release, suggesting
      that they were unable to sustain drug release into the solution for long periods
      of time. Given that no single method of myopia control has yet shown itself to be
      completely effective in preventing myopia progression, a combination of optical
      and pharmaceutical devices comprising a drug delivering contact lens presents a
      novel solution that warrants further investigation.

PMID- 29213205
TI  - Hypercapnic Ventilatory Response in the Weaning of Patients with Prolonged
      Mechanical Ventilation.
AB  - Objective: To investigate whether hypercapnic ventilatory response (defined as
      the ratio of the change in minute ventilation [[Formula: see text]] to the change
      in end-tidal partial pressure of carbon dioxide [DeltaPETCO2 ]) is a predictor of
      successful weaning in patients with prolonged mechanical ventilation (PMV) and to
      determine a reference value for clinical use. Methods: A hypercapnic challenge
      test was performed on 32 PMV subjects (average age: 74.3 years +/- 14.9 years).
      The subjects were divided into two groups (i.e., weaning successes and weaning
      failures) and their hypercapnic ventilatory responses were compared. Results: PMV
      subjects had an overall weaning rate of 68.8%. The weaning-success and weaning
      failure groups had hypercapnic ventilatory responses ([Formula: see text]) of
      0.40 +/- 0.16 and 0.28 +/- 0.12 L/min/mmHg, respectively (P = .036). The area
      under the receiver operating characteristic curve was 0.716 of the hypercapnic
      ventilatory response, and the practical hypercapnic ventilatory response cut-off
      point for successful weaning was 0.265 with 86.4% sensitivity and 50%
      specificity. Conclusions: PMV subjects who failed weaning had a lower hypercapnic
      ventilatory response than successfully weaned subjects. However, the prediction
      capacity of this test, assessed by the area under the receiver operating
      characteristic (ROC) curve, poorly predicted weaning outcome.

PMID- 29213206
TI  - HIV transmission clusters among injecting drug users in Romania.
AB  - : Injection drug use is increasingly an important route of HIV transmission in
      Romania (from 1.5% of the newly diagnosed cases prior to 2010 to 31% in 2013). In
      this study we investigated the viral characteristics and relationships in newly
      HIV infected persons who inject drugs in Bucharest, Romania. Results: HIV-1 pol
      sequencing, followed by phylogenetic and clustering analysis was performed on
      blood from 37 injecting drug users (IDUs) newly diagnosed with HIV infection.
      While HIV subtype F1, the dominant strain in Romania since 1990, remains
      prevalent, new subtypes were found including G, B, B/G and B/F recombinants.
      Overall, 27 of the available sequences (72.9%) clustered with at least one other.
      Network and phylogenetic analysis revealed tight monophyletic clusters for both
      subtypes F and G, with short genetic distances between sequences, suggesting
      recent numerous acute to acute transmissions or single burst-type episodes. No
      transmitted drug-resistance mutations were identified. Greater immunosuppression
      was present in subjects forming the subtype G cluster, possibly indicating a
      faster rate of progression associated with this subtype. Conclusions: The recent
      increasing numbers of IDU related HIV transmissions in Bucharest, has resulted in
      closely-knit transmission networks that maychange the genetic profile of the
      local HIV epidemic.

PMID- 29213207
TI  - Ontogenetic variability in old and new collections of Dicranophyllum gallicum
      Grand'Eury from the late Palaeozoic of Europe.
AB  - Dicranophyllum gallicum Grand'Eury is described by means of a morphometric
      analysis of eighty two samples from various old and new localities in western and
      central Europe. Stem, leaf cushions, leaf scars, leaves, axillary structures and
      potential seeds are described in detail, and discussed in comparison to earlier
      studies. The encountered variability in size and structure is shown to be higher
      than what was described earlier. The organisation of the leaf cushion and scar
      density vary gradually with the stem width, while stratigraphic position and
      ecology do not relate to it. It is concluded that the described variability
      represents an ontogenetic feature rather than a phylogenetic or ecologic one. The
      juvenile plants are characterised by small stems, a high leaf scar density and
      elongated leaf cushions with a dominant apical field, while mature specimens are
      characterized by a wide stem, a relatively low leaf scar density and relatively
      wide leaf cushions with a pronounced basal field. Axillary shoots and potential
      seeds of D. gallicum are described and illustrated in detail for the first time.
      A reconstruction based on the studied material is presented.

PMID- 29213208
TI  - Awareness of malaria and treatment-seeking behaviour among persons with acute
      undifferentiated fever in the endemic regions of Myanmar.
AB  - Background: Myanmar has a high burden of malaria with two-third of the population
      at risk of malaria. One of the basic elements of the Roll Back Malaria Initiative
      to fight against malaria is early diagnosis and treatment within 24 h of fever.
      Public awareness about malaria is a key factor in malaria prevention and control
      and in improving treatment-seeking behaviour. Methods: A large community-based
      survey was carried out in 27 townships of malaria endemic regions in Myanmar in
      2015 which reported on the knowledge, behaviour and practices around malaria in
      the general population. We used the data already collected in this survey to
      assess (i) general public awareness of malaria and (ii) treatment-seeking
      behaviour and associated factors among persons with acute undifferentiated fever.
      Results: A total of 6597 respondents from 6625 households were interviewed
      (response rate of 99.5%). About 85% of the respondents were aware that mosquito
      bite was the mode of transmission of malaria and 90% mentioned that malaria was
      preventable. However, only 16% of the respondents knew about anti-malaria drug
      resistance. There were certain misconceptions about the transmission of malaria
      such as dirty water, same blood group, sharing shelter, sleeping/eating together
      and poor hygiene. Health facility staff were the most common source of
      information about malaria (80%). Nearly one-fourth (23%) of the respondents with
      fever resorted to self-medication. Around 28% of the respondents with fever
      underwent blood testing, less than half of whom (44%) were tested within 24 h.
      Elderly age group, females, those with poor knowledge about malaria and those
      residing in non-Regional Artemisinin Resistance Initiative townships were
      associated with poor treatment-seeking behaviour in case of fever. Conclusion:
      Although there is fair knowledge on mosquito bite as a mode of transmission and
      prevention of malaria, there are some misconceptions about transmission of
      malaria. Those having poor knowledge about malaria have poor treatment-seeking
      behaviour. A considerable number of respondents seek care from informal care
      providers and seek care late. Thus, there is a need to promote awareness about
      the role of early diagnosis and appropriate treatment and address misconceptions
      about transmission of malaria.

PMID- 29213209
TI  - Creep and cracking of concrete hinges: insight from centric and eccentric
      compression experiments.
AB  - Existing design guidelines for concrete hinges consider bending-induced tensile
      cracking, but the structural behavior is oversimplified to be time-independent.
      This is the motivation to study creep and bending-induced tensile cracking of
      initially monolithic concrete hinges systematically. Material tests on plain
      concrete specimens and structural tests on marginally reinforced concrete hinges
      are performed. The experiments characterize material and structural creep under
      centric compression as well as bending-induced tensile cracking and the
      interaction between creep and cracking of concrete hinges. As for the latter two
      aims, three nominally identical concrete hinges are subjected to short-term and
      to longer-term eccentric compression tests. Obtained material and structural
      creep functions referring to centric compression are found to be very similar.
      The structural creep activity under eccentric compression is significantly larger
      because of the interaction between creep and cracking, i.e. bending-induced
      cracks progressively open and propagate under sustained eccentric loading. As for
      concrete hinges in frame-like integral bridge construction, it is concluded (i)
      that realistic simulation of variable loads requires consideration of the here
      studied time-dependent behavior and (ii) that permanent compressive normal forces
      shall be limited by 45% of the ultimate load carrying capacity, in order to avoid
      damage of concrete hinges under sustained loading.

PMID- 29213210
TI  - German S3 Guideline Nonrestorative Sleep/Sleep Disorders, chapter "Sleep-Related
      Breathing Disorders in Adults," short version: German Sleep Society (Deutsche
      Gesellschaft fur Schlafforschung und Schlafmedizin, DGSM).

PMID- 29213211
TI  - Black holes, hidden symmetries, and complete integrability.
AB  - The study of higher-dimensional black holes is a subject which has recently
      attracted vast interest. Perhaps one of the most surprising discoveries is a
      realization that the properties of higher-dimensional black holes with the
      spherical horizon topology and described by the Kerr-NUT-(A)dS metrics are very
      similar to the properties of the well known four-dimensional Kerr metric. This
      remarkable result stems from the existence of a single object called the
      principal tensor. In our review we discuss explicit and hidden symmetries of
      higher-dimensional Kerr-NUT-(A)dS black hole spacetimes. We start with discussion
      of the Killing and Killing-Yano objects representing explicit and hidden
      symmetries. We demonstrate that the principal tensor can be used as a "seed
      object" which generates all these symmetries. It determines the form of the
      geometry, as well as guarantees its remarkable properties, such as special
      algebraic type of the spacetime, complete integrability of geodesic motion, and
      separability of the Hamilton-Jacobi, Klein-Gordon, and Dirac equations. The
      review also contains a discussion of different applications of the developed
      formalism and its possible generalizations.

PMID- 29213212
TI  - Implementation and feasibility of the stroke nursing guideline in the care of
      patients with stroke: a mixed methods study.
AB  - Background: Nurses often have difficulties with using interdisciplinary stroke
      guidelines for patients with stroke as they do not focus sufficiently on nursing.
      Therefore, the Stroke Nursing Guideline (SNG) was developed and implemented. The
      aim of this study was to determine the implementation and feasibility of the SNG
      in terms of changes in documentation and use of the guideline in the care of
      stroke patients on Neurological and Rehabilitation wards, barriers and
      facilitators, and nurses' and auxiliary nurses' view of the implementation.
      Methods: A sequential explorative mixed method design was used including pre-test
      post-test measures and post intervention focus groups interviews. For the
      quantitative part retrospective electronic record data of nursing care was
      collected from 78 patients and prospective measures with Barriers and
      Facilitators Assessment Instrument (BFAI) and Quality Indicator Tool (QIT) from
      33 nursing staff including nurses and auxiliary nurses. In the qualitative part
      focus groups interviews were conducted with nursing staff on usefulness of the
      SNG and experiences with implementation. Results: Improved nursing documentation
      was found for 23 items (N = 37), which was significant for nine items focusing
      mobility (p = 0.002, p = 0.024, p = 0.012), pain (p = 0.012), patient teaching (p
      = 0.001, p = 0.000) and discharge planning (p = 0.000, p = 0.002, p = 0.004).
      Improved guideline use was found for 20 QIT-items (N = 30), with significant
      improvement on six items focusing on mobility (p = 0.023), depression (p = 0.033,
      p = 0.025, p = 0.046, p = 0.046), discharge planning (p = 0.012). Facilitating
      characteristics for change were significantly less for two of four BFAI
      subscales, namely Innovation (p = 0.019) and Context (p = 0.001), whereas no
      change was found for Professional and Patient subscales. The findings of the
      focus group interviews showed the SNG to be useful, improving and providing
      consistency in care. The implementation process was found to be successful as
      essential components of nursing rehabilitation were defined and integrated into
      daily care. Conclusion: Nursing staff found the SNG feasible and implementation
      successful. The SNG improved nursing care, with increased consistency and more
      rigorous functional exercises than before. The SNG provides nurses and auxiliary
      nurses with an important means for evidence based care for patients with stroke.
      Several challenges of implementing this complex nursing intervention surfaced
      which mandates ongoing attention.

PMID- 29213213
TI  - "From resistance to challenge": child health service nurses experiences of how a
      course in group leadership affected their management of parental groups.
AB  - Background: All parents in Sweden are invited to child health service (CHS)
      parental groups, however only 49% of the families participate. The way the
      parental groups are managed has been shown to be of importance for how parents
      experience the support and CHS nurses describe feeling insecure when running the
      groups. Lack of facilitation, structure and leadership might jeopardise the
      potential benefit of such support groups. This study describes CHS nurses'
      experiences of how a course in group leadership affected the way they ran their
      parental groups. Methods: A course in group leadership given to 56 CHS nurses was
      evaluated in focus group interviews 5-8 months after the course. Results: The
      nurses felt strengthened in their group leader role and changed their leadership
      methods. The management of parental groups was after the course perceived as an
      important work task and the nurses included time for planning, preparation and
      evaluation, which they felt improved their parental groups. Parental
      participation in the activities in the group had become a key issue and they used
      their new exercises and tools to increase this. They expressed feeling more
      confident and relaxed in their role as group leaders and felt that they could
      adapt their leadership to the needs of the parents. Conclusions: Specific
      training might strengthen the CHS nurses in their group leader role and give them
      new motivation to fulfil their work with parental groups. Trial registration: 
      Clinical Trials.gov ID: NCT02494128.

PMID- 29213214
TI  - ROR2 receptor promotes the migration of osteosarcoma cells in response to Wnt5a.
AB  - Background: We have reported that the phosphatidylinositol-3 kinase
      (PI3K)/Akt/RhoA signaling pathway mediates Wnt5a-induced cell migration of
      osteosarcoma cells. However, the specific receptors responding to Wnt5a ligand
      remain poorly defined in osteosarcoma metastasis. Methods: Wound healing assays
      were used to measure the migration rate of osteosarcoma cells transfected with
      shRNA or siRNA specific against ROR2 or indicated constructs. We evaluated the
      RhoA activation in osteosarcoma MG-63 and U2OS cells with RhoA activation assay.
      A panel of inhibitors of PI3K and Akt treated osteosarcoma cells and blocked
      kinase activity. Western blotting assays were employed to measure the expression
      and activation of Akt. Clonogenic assays were used to measure the cell
      proliferation of ROR2-knockdown or ROR2-overexpressed osteosarcoma cells.
      Results: Wnt5a-induced osteosarcoma cell migration was largely abolished by shRNA
      or siRNA specific against ROR2. Overexpression of RhoA-CA (GFP-RhoA-V14) was able
      to rescue the Wnt5a-induced cell migration blocked by ROR2 knockdown. The Wnt5a
      induced activation of RhoA was mostly blocked by ROR2 knockdown, and elevated by
      ROR2 overexpression, respectively. Furthermore, we found that Wnt5a-induced cell
      migration was significantly retarded by RhoA-siRNA transfection or pretreatment
      of HS-173 (PI3Kalpha inhibitor), MK-2206 (Akt inhibitor), A-674563 (Akt1
      inhibitor), or CCT128930 (Akt2 inhibitor). The activation of Akt was upregulated
      or downregulated by transfected with ROR2-Flag or ROR2-siRNA, respectively.
      Lastly, Wnt5a/ROR2 signaling does not alter the cell proliferation of MG-63
      osteosarcoma cells. Conclusions: Taken together, we demonstrate that ROR2
      receptor responding to Wnt5a ligand activates PI3K/Akt/RhoA signaling and
      promotes the migration of osteosarcoma cells.

PMID- 29213215
TI  - CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma
      through regulating PI3K-AKT signalling.
AB  - Background: Human chemokine like factor (CKLF)-like MAL and related proteins for
      vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been
      shown to involved and may function as a tumour suppressor in tumorigenesis. The
      current study aimed to investigate the expression and function of CMTM5 in human
      hepatocellular carcinoma (HCC). Methods: CMTM5 expression was examined by
      immunohistochemistry, and its clinical significance was analysed in 76 HCC
      specimens. The role and molecular mechanisms of CMTM5 in cell proliferation,
      apoptosis and invasion were examined in vitro and in vivo. Results: CMTM5
      expression was significantly downregulated in HCC tissues as well as cell lines.
      The expression of CMTM5 was absent in 77.6% of HCC tissues compared with 3.9% in
      normal liver tissues. Low CMTM5 expression was significantly correlated with poor
      overall survival in patients with HCC (P = 0.009). Restoring CMTM5 expression in
      Huh7 cells significantly inhibited cell growth, promoted cell apoptosis, and
      reduced cell metastatic and invasion ability compared with mock transfected cells
      in vitro. Overexpression of CMTM5 also suppressed xenograft tumour growth in vivo
      in a HCC xenograft model. Reduced cell growth and metastasis ability mediated by
      CMTM5 overexpression was associated with downregulation of PI3K/AKT and its
      downstream Bcl2, cyclinD1, cyclinE, MMP2 and MMP9 expressions, and an
      upregulation of p21, Bax, Bad, cleaved caspase3 expressions. Conclusions: Our
      data suggest that CMTM5 might function as a tumour suppressor in human HCC, and
      represent a valuable potential therapeutic target for HCC.

PMID- 29213216
TI  - Tumor-infiltrating CD4+ T cells in patients with gastric cancer.
AB  - Background: T lymphocytes play an indispensably important role in clearing virus
      and tumor antigen. There is little knowledge about impacts of inhibitory
      molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of
      gastric cancer (GC). This study investigated the distribution of tumor
      infiltrating T-cells subset and the differentiation as well as inhibitory
      phenotype of T-cells from blood and tissues of GC patients. Materials and
      methods: Patients with GC diagnosed on the basis of pre-operative staging and
      laparotomy findings were approached for enrollment between 2014 and 2015 at the
      Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis
      based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-gamma
      staining assay is conducted. Statistical analysis is performed to show
      significance. Results: The results showed that the percentage of CD4+ T-cells
      among CD3+ cells in tumors was significantly higher than that in the matched
      paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+,
      Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells
      from patients with GC compared to their expressions on corresponding peripheral
      blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in
      restoring tumor infiltrating T-cells' production of interferon-gamma (IFN-gamma).
      Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-gamma
      secretion by CD4+ T-cells. Conclusion: The results suggested that the
      composition, inhibitors, and location of the immune infiltrate should be
      considered when evaluating antitumor immunotherapy. A new insight into the
      mechanisms underlying T cell dysfunction is provided.

PMID- 29213217
TI  - Increased expression of MARCH8, an E3 ubiquitin ligase, is associated with growth
      of esophageal tumor.
AB  - Background: Herein, for the first time, we report aberrant expression of membrane
      associated RING-CH8 (MARCH8) in human esophageal squamous cell carcinoma. MARCH8
      is a member of the recently discovered MARCH family of really interesting new
      genes (RING) E3 ligases. Though initial studies primarily focused on its
      immunomodulatory role, the newly discovered targets of this E3 ligase point
      towards its possible role in other biological processes such as embryogenesis and
      inhibition of apoptosis. However, its relevance in cancers is yet to be
      elucidated. Methods: We carried out quantitative real time PCR and
      immunohistochemistry to examine the levels of MARCH8 mRNA and protein in
      esophageal squamous cell carcinoma tissues. The role of MARCH8 in esophageal
      cancer cells was evaluated by cell proliferation, clonogenic and
      migration/invasion assays and flow cytometry with MARCH8 gene knockdown. Results:
      Significantly increased expression of MARCH8 mRNA was found in esophageal
      squamous cell carcinoma as compared to distant matched non-malignant tissues (p =
      0.024, AUC = 0.654). Immunohistochemical analysis revealed overexpression of
      MARCH8 protein in 86% of esophageal squamous cell carcinoma tissues (p < 0.001,
      AUC = 0.908). Interestingly, intense nuclear staining of MARCH8 protein was
      detected in cancer cells in addition to its cytoplasmic expression. Knockdown of
      MARCH8 resulted in decreased proliferation, migration, invasion and clonogenic
      potential of esophageal cancer cells. In addition to this, silencing of MARCH8
      induced apoptosis in esophageal cancer cells which was measured by cell cycle
      distribution assay which showed increase in sub G0 and G2/M populations (cell
      death) and decrease in S-phase population. To further check the type of apoptosis
      induced by MARCH8 silencing, annexin assay was performed which showed significant
      increase in the number of cells in early apoptotic phase. Conclusions: Overall,
      increased expression of MARCH8 gene in preneoplastic and neoplastic esophageal
      tissues and its knockdown effect on cancer cell properties demonstrated herein
      points towards the potential role of this protein in esophageal tumorigenesis.

PMID- 29213218
TI  - Tiotropium in asthma: back to the future of anticholinergic treatment.
AB  - Asthma is among the most common chronic diseases worldwide; however, despite
      progresses in the understanding of the patho-physiological mechanisms and
      advances in the development of new therapeutic options and strategies, the
      disease remains uncontrolled in a not trivial proportion of subjects. Thus, the
      need of new molecules to treat the underlying biological and functional
      abnormalities and to control symptoms is strongly advocated by clinicians. In
      this scenario, the most recent GINA guidelines have included the use of
      tiotropium bromide in the most severe and uncontrolled forms of the disease, in
      addition to treatment with inhaled corticosteroid plus long acting beta
      adrenergic agents. Indeed, a large body of evidence has accumulated to support
      the use of tiotropium bromide in asthma. The current review paper provides a
      state of the art systematic revision of findings on the efficacy and safety of
      tiotropium in the adult and paediatric asthma population. To this aim, electronic
      searches were undertaken in the most common scientific databases from the date of
      inception to March 2017. Robust and high quality evidence showed that tiotropium
      is effective and safe in both adults and children/adolescents. Predictive markers
      of response have been also suggested, as well as cost-benefit analyses reported.
      The tiotropium bronchodilator effect seems to be not solely related to the
      reduction of the smooth muscle tone. However, the observations on anti
      inflammatory properties or reduction in mucus production, despite highly
      interesting, have been only demonstrated in in vitro studies and animal models,
      therefore advocating for further specifically designed investigations.

PMID- 29213219
TI  - A Review on Bone Mineral Density Loss in Total Knee Replacements Leading to
      Increased Fracture Risk.
AB  - The link between low bone mineral density (BMD) scores leading to greater
      fracture risk is well established in the literature; what is not fully understood
      is the impact of total knee replacements/revisions or arthroplasties on BMD
      levels. This literature review attempts to answer this question. Several
      different databases using specific key terms were searched, with additional
      papers retrieved via bibliographic review. Based on the available evidence, total
      knee replacements/revisions and arthroplasties lower BMD and thus increase
      fracture risk. This review also addresses the possible implications of this
      research and possible options to reduce this risk.

PMID- 29213220
TI  - The proteins cleaved by endogenous tryptic proteases in normal EDTA plasma by C18
      collection of peptides for liquid chromatography micro electrospray ionization
      and tandem mass spectrometry.
AB  - The tryptic peptides from ice cold versus room temperature plasma were identified
      by C18 liquid chromatography and micro electrospray ionization tandem mass
      spectrometry (LC-ESI-MS/MS). Samples collected on ice showed low levels of
      endogenous tryptic peptides compared to the same samples incubated at room
      temperature. Plasma on ice contained peptides from albumin, complement, and
      apolipoproteins and others that were observed by the X!TANDEM and SEQUEST
      algorithms. In contrast to ice cold samples, after incubation at room
      temperature, greater numbers of tryptic peptides from well characterized plasma
      proteins, and from cellular proteins were observed. A total of 583,927 precursor
      ions and MS/MS spectra were correlated to 94,669 best fit peptides that reduced
      to 22,287 correlations to the best accession within a gene symbol and to 7174
      correlations to at least 510 gene symbols with >= 5 independent MS/MS
      correlations (peptide counts) that showed FDR q-values ranging from E-9 (i.e. FDR
      = 0.000000001) to E-227. A set of 528 gene symbols identified by X!TANDEM and
      SEQUEST including C4B showed >= fivefold variation between ice cold versus room
      temperature incubation. STRING analysis of the protein gene symbols observed from
      endogenous peptides in normal plasma revealed an extensive protein-interaction
      network of cellular factors associated with cell signalling and regulation, the
      formation of membrane bound organelles, cellular exosomes and exocytosis network
      proteins. Taken together the results indicated that a pool of cellular proteins,
      or protein complexes, in plasma are apparently not stable and degrade soon after
      incubation at room temperature.

PMID- 29213221
TI  - Omalizumab in Children with Severe Allergic Asthma: The Italian Real-Life
      Experience.
AB  - Background: Anti-IgE treatment represents a major breakthrough in the therapeutic
      management of severe allergic asthma. To date, omalizumab is the only biological
      drug currently licensed as add-on therapy in children aged > 6 years with
      moderate-to-severe and severe allergic asthma uncontrolled after treatment with
      high dose of inhaled corticosteroids plus long-acting inhaled beta2-agonist. The
      clinical efficacy and safety of omalizumab treatment in the pediatric population
      has been extensively documented in specific trials and consistently expanded from
      real-life studies. Our aim is to describe the impact of omalizumab on asthma
      management, by reporting the results of the first Italian multicenter
      observational study conducted in children and adolescents with severe allergic
      asthma. Methods: The study was a 1-year real-life multicenter survey conducted in
      13 pediatric allergy and pulmonology tertiary centers in Italy. All patients with
      confirmed severe allergic asthma from whom Omalizumab add-on treatment was
      initiated between 2007 and 2015 were included in the study. Results: Forty-seven
      patients with severe allergic asthma were included in the study. A significant
      reduction in the number of asthma exacerbations was observed during treatment
      with omalizumab, when compared with the previous year (1.03 vs 7.2 after 6 months
      (p<0.001) and 0.8 after 12 months (p<0.001), respectively). Hospital admissions
      were reduced by 96%. At 12 months, forced expiratory volume in 1 s improved and a
      corticosteroid sparing effect was observed.No serious adverse events were
      reported during the follow-up period of 12 months. Conclusion: The results of the
      first Italian multicenter observational study confirmed that omalizumab is an
      effective and safe add-on therapy in uncontrolled severe allergic asthma in
      children.

PMID- 29213222
TI  - Antiplasmodial Compounds from Leaves of Dodonaea angustifolia.
AB  - Background: Dodonaea angustifolia is used in Ethiopian traditional medicine to
      treat malaria. The objective of this work was to conduct bioassay guided
      fractionation of the leaves of D. angustifolia using Plasmodium berghei infected
      mice. Method: The antiplasmodial activity of the extracts and pure compounds was
      evaluated using the standard Peter's four-day suppressive method. The structures
      of isolated compounds were elucidated using chemi-cal and spectroscopic methods.
      Results: In this study, the ethyl acetate soluble portion of the 80% aqueous MeOH
      extract of the leaves significantly suppressed parasitaemia in Plasmodium berghei
      infected mice (80.28% at 150 mg/kg). Three active compounds which exhibited
      significant percent suppression of parasitaemia by 81% at 40 mg/kg, 80% at 50
      mg/kg and 70% at 40 mg/kg, respectively were identified. These are the flavanone
      pinocembrin (1), the flavanol santin (2) and the clerodane diterpene 2-hydroxy
      15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (3). Under similar conditions,
      chloroquine suppressed parasitaemia by 100% at 25 mg/kg. Chemical study of the
      ethanol extract of the leaves yielded 5,7,4'-trihydroxy-3,6-dimethoxyflavone (4),
      ent-16-hydroxy-labdan-3alpha,8beta-dihydroxy,13(14)-en-15,16-olide (5) and 5,6,7
      trihydroxy-3,4'-dimethoxyflavone (6). Compound 6 has not been reported before as
      a natural product. Conclusion: From the leaves of D. angustifolia, three
      compounds with significant antiplasmodial activi-ties were isolated and
      characterized, with pinocembrin as the most active compound.

PMID- 29213223
TI  - Compositional Monosaccharide Analysis of Morus nigra Linn by HPLC and HPCE
      Quantitative Determination and Comparison of Polysaccharide from Morus nigra Linn
      by HPCE and HPLC.
AB  - Background: Morus nigra Linn is not only treated as health food but also medicine
      in Chinese history. Objective: Here, we have extracted and separated the
      heteroglycan to monosaccharides of the dry fruits. Method: After heteroglycan
      being hydrolysised, then were we derivatived the monosaccharides with 1-phenyl-3
      methyl-5-pyrazolone (PMP), and then subsequently HPCE and HPLC were used to
      separate. HPCE, which held an uncoated capillary (d=75MUm) and detected by PDA at
      245 nm with borate buffer, the voltage was set at 15 kV and capillary temperature
      was 25 degrees C. There is Yilite column (Hypersil BDS C18 5MUm, 4.6mm*250mm)
      with HPLC and detected by UV at 245 nm and capillary temperature 25 degrees C.The
      High Performance capillary electrophoresis method and High Performance Liquid
      Chromatog-raphy method were compared on monosaccharide composition and
      quantitative determination of polysac-charide from the black mulberry. Results:
      Through several indicators including standard curve, precision, reproducibility,
      stability and recovery rate, the result of the two methods is basically
      consistent while they have complementary ad-vantages. Conclusion: Both methods
      are suitable for the determination of the black mulberry polysaccharide, but each
      has its own merits.

PMID- 29213224
TI  - Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and
      Its Potential Therapeutic Targets: Insights from Modeling.
AB  - Gain-of-function mutations in the pore-forming subunit of IKs channels, KCNQ1,
      lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant IKs
      channels cause SQTS and the possibility of IKs-specific pharmacological treatment
      remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect
      on IKs gating properties and changes in the action potentials (AP) of human
      ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of
      expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate
      human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes
      with and without beta-adrenergic stimulation. V141M KCNQ1 caused a gain-of
      function in IKs characterized by increased current density, faster activation,
      and slower deactivation leading to IKs accumulation. V141M KCNQ1 also caused a
      leftward shift of the conductance-voltage curve compared to wild type (WT) IKs
      (V1/2 = 33.6 +/- 4.0 mV for WT, and 24.0 +/- 1.3 mV for heterozygous V141M). A
      Markov model of heterozygous V141M mutant IKs was developed and incorporated into
      the O'Hara-Rudy model. Compared to the WT, AP simulations demonstrated marked
      rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS
      phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M
      AP simulations, especially under beta-adrenergic stimulation. Computational
      simulations identified specific IK1 blockade as a beneficial pharmacologic target
      for reducing the transmural APD heterogeneity associated with V141M KCNQ1
      mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural
      APD heterogeneity under beta-adrenergic stimulation. Computational simulations
      identified IK1 blockers as a potential antiarrhythmic drug of choice for SQTS.

PMID- 29213225
TI  - Role of blue dye for sentinel lymph node detection in early endometrial cancer.
AB  - Background: Sentinel Lymphonode analysis has become a barely new and innovative
      way to treat early stages of endometrial cancer (Ballester et al., Lancet Oncol
      469-476, 2011; Buda et al., Ann Surg Oncol 2975-81, 2016). Indocyanine green
      cervical injection is considered gold standard for mapping nodes' drainage. Blue
      dye is used as a valid alternative in many centers, due to the lower cost of
      execution. The objective of this video is to prove that methylene blue dye's
      cervical injection is a valid and "low-cost" method to obtain mapping of
      lymphatic drainage in patient with early endometrial cancer. Methods: Fifty-four
      year old women, with a recent diagnosis of endometrial cancer IA G2, we performed
      a radical Hysterectomy type A. We diluted in equal proportions the blue dye and
      saline and injected 1 cl in depth and 1 cl on the surface of the cervix, at 3
      o'clock and 9 o'clock. After 20 min, it was shown with precision the lymphatic
      drainage until the first lymph node station from both sides. Results: One
      external iliac lymph node and one obturator were resected on the left side and
      one external iliac on the right side. On histological analysis, none of the lymph
      nodes had any location of metastasis, neither micro-metastasis. Myometrial
      infiltration was 8/19 mm. Conclusions: Blue dye cervical injection is a "low
      cost", safe, and satisfactory procedure to point out Sentinel Lymph Node of
      uterus drainage. Other tracers, such as indocyanine green, are widely used in
      gynecological oncology, but with a higher cost of the product and the needing of
      a dedicated optical filter to be shown on human view.

PMID- 29213226
TI  - Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and
      Implementation.
AB  - Transcranial direct current stimulation (tDCS) is a popular brain stimulation
      method that is used to modulate cortical excitability, producing facilitatory or
      inhibitory effects upon a variety of behaviors. There is, however, a current lack
      of consensus between studies, with many results suggesting that polarity-specific
      effects are difficult to obtain. This article explores some of these differences
      and highlights the experimental parameters that may underlie their occurrence. We
      provide a general, practical snapshot of tDCS methodology, including what it is
      used for, how to use it, and considerations for designing an effective and safe
      experiment. Our aim is to equip researchers who are new to tDCS with the
      essential knowledge so that they can make informed and well-rounded decisions
      when designing and running successful experiments. By summarizing the varied
      approaches, stimulation parameters, and outcomes, this article should help inform
      future tDCS research in a variety of fields.

PMID- 29213228
TI  - Adenosine A1-A2A Receptor Heteromer as a Possible Target for Early-Onset
      Parkinson's Disease.

PMID- 29213227
TI  - Targeted Delivery of Mitochondrial Calcium Channel Regulators: The Future of
      Glaucoma Treatment?

PMID- 29213229
TI  - Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear
      Neurotransmission.
AB  - Approximately 15% of American adults report some degree of difficulty hearing in
      a noisy environment or have auditory filtering difficulties. There are objective
      clinical tests of auditory filtering, yet few tests exist for mouse models that
      do not rely on extensive training. We have used reflex modification audiometry
      (RMA) and developed exclusion criteria for the mouse model. This RMA based test
      makes use of the acoustic startle response (ASR) and the ability of prepulses to
      inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability
      to detect prepulse signals presented in quiet or embedded in masking noise. We
      have studied PPI behavior across four inbred mouse strains with normal cochlear
      function and developed pre-testing exclusion criteria and test/retest reliability
      measures. Moreover, because both the medial (MOC) and the lateral (LOC)
      olivocochlear efferent feedback systems have been proposed to improve auditory
      behavior performance, especially in noisy backgrounds, we have examined PPI
      abilities in mice (with their littermate controls) either lacking the MOC
      receptor subunit alpha9 nicotinic acetylcholine receptor [alpha9 nAChR (-/-)] or
      expressing an overactive receptor [Ld'T mutation in alpha9 nAChR KI], or lacking
      an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [alphaCGRP (
      /-)] only in the CNS. Because CGRP receptor formation has been shown to mature
      from juvenile to adult ages, we also studied if this maturation would be
      reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in
      adult alphaCGRP (-/-) animals. We show that 50% PPI response thresholds (sound
      level with 50% correct responses) in quiet are decreased in the (-/-) alpha9
      nAChR animals, and 50% PPI responses are increased for mice with an overactive
      receptor (alpha9 nAChR KI) and are increased in adult mice lacking alphaCGRP (-/
      ). However, in background noise, only mice lacking alphaCGRP exhibited increased
      50% PPI response thresholds, as there were no significant differences between
      alpha9 nAChR adult mouse lines and their littermate controls. These findings
      suggest that MOC and LOC olivocochlear neurotransmission work in tandem to
      improve behavioral responses to sound. These experiments further pave the way for
      rapid behavioral hearing assessments in other mouse models.

PMID- 29213230
TI  - Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves.
AB  - The pannexin family of channels consists of three members-pannexin-1 (Panx1),
      pannexin-2 (Panx2), and pannexin-3 (Panx3) that enable the exchange of
      metabolites and signaling molecules between intracellular and extracellular
      compartments. Pannexin-mediated release of intracellular ATP into the
      extracellular space has been tied to a number of cellular activities, primarily
      through the activity of type P2 purinergic receptors. Previous work indicates
      that the opening of Panx1 channels and activation of purinergic receptors by
      extracellular ATP may cause inflammation and apoptosis. In the CNS (central
      nervous system) and PNS (peripheral nervous system), coupled pannexin, and P2
      functions have been linked to peripheral sensitization (pain) pathways.
      Purinergic pathways are also essential for other critical processes in the PNS,
      including myelination and neurite outgrowth. However, whether such pathways are
      pannexin-dependent remains to be determined. In this study, we use a Panx1
      knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP
      mediated signaling pathway to fill gaps in our understanding of Panx1
      localization in peripheral nerves, roles for Panx1 in axonal outgrowth and
      myelination, and neurite extension. Our data show that Panx1 is localized to
      axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of
      Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate
      in cultured dorsal root ganglia (DRG) neurons. Furthermore, genetic knockout of
      Panx1 or inhibition of components of purinergic signaling, by treatment with
      probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG
      explants compared to untreated wild-types. Our findings suggest that Panx1
      regulates axonal growth in the peripheral nervous system.

PMID- 29213231
TI  - The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.
AB  - Sleep plays important roles in sensory and motor memory consolidation. Sleep
      oscillations, reflecting neural population activity, involve the reactivation of
      learning-related neurons and regulate synaptic strength and, thereby affect
      memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely
      associated with memory consolidation. For example, slow-wave power is regulated
      in an experience-dependent manner and correlates with acquired memory.
      Furthermore, manipulating slow waves can enhance or impair memory consolidation.
      During slow wave sleep, inter-areal interactions between the cortex and
      hippocampus (HC) have been proposed to consolidate declarative memory; however,
      interactions for non-declarative (HC-independent) memory remain largely
      uninvestigated. We recently showed that the directional influence in a slow-wave
      range through a top-down cortical long-range circuit is involved in the
      consolidation of non-declarative memory. At the synaptic level, the average
      cortical synaptic strength is known to be potentiated during wakefulness and
      depressed during sleep. Moreover, learning causes plasticity in a subset of
      synapses, allocating memory to them. Sleep may help to differentiate synaptic
      strength between allocated and non-allocated synapses (i.e., improving the signal
      to-noise ratio, which may facilitate memory consolidation). Herein, we offer
      perspectives on inter-areal interactions and synaptic plasticity for memory
      consolidation during sleep.

PMID- 29213233
TI  - Multisensory and Modality-Specific Influences on Adaptation to Optical Prisms.
AB  - Visuo-motor adaptation to optical prisms displacing the visual scene (prism
      adaptation, PA) is a method used for investigating visuo-motor plasticity in
      healthy individuals and, in clinical settings, for the rehabilitation of
      unilateral spatial neglect. In the standard paradigm, the adaptation phase
      involves repeated pointings to visual targets, while wearing optical prisms
      displacing the visual scene laterally. Here we explored differences in PA, and
      its aftereffects (AEs), as related to the sensory modality of the target. Visual,
      auditory, and multisensory - audio-visual - targets in the adaptation phase were
      used, while participants wore prisms displacing the visual field rightward by 10
      degrees . Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive
      straight-ahead shifts were measured. Pointing to auditory and to audio-visual
      targets in the adaptation phase produces proprioceptive, visual-proprioceptive,
      and auditory-proprioceptive AEs, as the typical visual targets did. This finding
      reveals that cross-modal plasticity effects involve both the auditory and the
      visual modality, and their interactions (Experiment 1). Even a shortened PA
      phase, requiring only 24 pointings to visual and audio-visual targets (Experiment
      2), is sufficient to bring about AEs, as compared to the standard 92-pointings
      procedure. Finally, pointings to auditory targets cause AEs, although PA with a
      reduced number of pointings (24) to auditory targets brings about smaller AEs, as
      compared to the 92-pointings procedure (Experiment 3). Together, results from the
      three experiments extend to the auditory modality the sensorimotor plasticity
      underlying the typical AEs produced by PA to visual targets. Importantly, PA to
      auditory targets appears characterized by less accurate pointings and error
      correction, suggesting that the auditory component of the PA process may be less
      central to the building up of the AEs, than the sensorimotor pointing activity
      per se. These findings highlight both the effectiveness of a reduced number of
      pointings for bringing about AEs, and the possibility of inducing PA with
      auditory targets, which may be used as a compensatory route in patients with
      visual deficits.

PMID- 29213234
TI  - Cognitive Mapping Based on Conjunctive Representations of Space and Movement.
AB  - It is a challenge to build robust simultaneous localization and mapping (SLAM)
      system in dynamical large-scale environments. Inspired by recent findings in the
      entorhinal-hippocampal neuronal circuits, we propose a cognitive mapping model
      that includes continuous attractor networks of head-direction cells and
      conjunctive grid cells to integrate velocity information by conjunctive encodings
      of space and movement. Visual inputs from the local view cells in the model
      provide feedback cues to correct drifting errors of the attractors caused by the
      noisy velocity inputs. We demonstrate the mapping performance of the proposed
      cognitive mapping model on an open-source dataset of 66 km car journey in a 3 km
      * 1.6 km urban area. Experimental results show that the proposed model is robust
      in building a coherent semi-metric topological map of the entire urban area using
      a monocular camera, even though the image inputs contain various changes caused
      by different light conditions and terrains. The results in this study could
      inspire both neuroscience and robotic research to better understand the neural
      computational mechanisms of spatial cognition and to build robust robotic
      navigation systems in large-scale environments.

PMID- 29213235
TI  - Changes in Predictive Task Switching with Age and with Cognitive Load.
AB  - Predictive control of movement is more efficient than feedback-based control, and
      is an important skill in everyday life. We tested whether the ability to
      predictively control movements of the upper arm is affected by age and by
      cognitive load. A total of 63 participants were tested in two experiments. In
      both experiments participants were seated, and controlled a cursor on a computer
      screen by flexing and extending their dominant arm. In Experiment 1, 20 young
      adults and 20 older adults were asked to continuously change the frequency of
      their horizontal arm movements, with the goal of inducing an abrupt switch
      between discrete movements (at low frequencies) and rhythmic movements (at high
      frequencies). We tested whether that change was performed based on a feed-forward
      (predictive) or on a feedback (reactive) control. In Experiment 2, 23 young
      adults performed the same task, while being exposed to a cognitive load half of
      the time via a serial subtraction task. We found that both aging and cognitive
      load diminished, on average, the ability of participants to predictively control
      their movements. Five older adults and one young adult under a cognitive load
      were not able to perform the switch between rhythmic and discrete movement (or
      vice versa). In Experiment 1, 40% of the older participants were able to
      predictively control their movements, compared with 70% in the young group. In
      Experiment 2, 48% of the participants were able to predictively control their
      movements with a cognitively loading task, compared with 70% in the no-load
      condition. The ability to predictively change a motor plan in anticipation of
      upcoming changes may be an important component in performing everyday functions,
      such as safe driving and avoiding falls.

PMID- 29213236
TI  - Embodied Cognition: A Challenging Road for Clinical Neuropsychology.

PMID- 29213232
TI  - Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin.
AB  - Visceral pain is generally poorly localized and characterized by hypersensitivity
      to a stimulus such as organ distension. In concert with chronic visceral pain,
      there is a high comorbidity with stress-related psychiatric disorders including
      anxiety and depression. The mechanisms linking visceral pain with these
      overlapping comorbidities remain to be elucidated. Evidence suggests that long
      term stress facilitates pain perception and sensitizes pain pathways, leading to
      a feed-forward cycle promoting chronic visceral pain disorders such as irritable
      bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the
      development of IBS, however the mechanisms responsible for the persistent effects
      of ELS on visceral perception in adulthood remain incompletely understood. In
      rodent models, stress in adult animals induced by restraint and water avoidance
      has been employed to investigate the mechanisms of stress-induce pain. ELS models
      such as maternal separation, limited nesting, or odor-shock conditioning, which
      attempt to model early childhood experiences such as neglect, poverty, or an
      abusive caregiver, can produce chronic, sexually dimorphic increases in visceral
      sensitivity in adulthood. Chronic visceral pain is a classic example of gene *
      environment interaction which results from maladaptive changes in neuronal
      circuitry leading to neuroplasticity and aberrant neuronal activity-induced
      signaling. One potential mechanism underlying the persistent effects of stress on
      visceral sensitivity could be epigenetic modulation of gene expression. While
      there are relatively few studies examining epigenetically mediated mechanisms
      involved in visceral nociception, stress-induced visceral pain has been linked to
      alterations in DNA methylation and histone acetylation patterns within the brain,
      leading to increased expression of pro-nociceptive neurotransmitters. This review
      will discuss the potential neuronal pathways and mechanisms responsible for
      stress-induced exacerbation of chronic visceral pain. Additionally, we will
      review the importance of specific experimental models of adult stress and ELS in
      enhancing our understanding of the basic molecular mechanisms of pain processing.

PMID- 29213237
TI  - Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in
      Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer
      Patients after Docetaxel.
AB  - Introduction: Conventional anti-androgen regimens were widely used as an
      initiation or combined androgen blockade (CAB) therapy in advanced prostate
      cancer patients. Currently, new androgen pathway inhibitors such as abiraterone
      acetate (AA) and enzalutamide had been proven effective in metastatic castration
      resistant prostate cancer. In this study, we attempt to analyze the role of
      conventional anti-androgen drugs as deferred CAB therapy in castration-resistant
      prostate cancer patients. Materials and Methods: From 2012 to 2017, 48 metastatic
      castration-resistant prostate cancer (CRPC) patients who received sequential
      treatments with primary androgen blockade, oral anti-androgen regimens, and
      docetaxel followed by AA treatment were included. We defined effective deferred
      CAB as any decline of PSA after add-on antiandrogen after CRPC. Patients were
      separated into effective and ineffective deferred CAB. Comparison between two
      groups in the first line androgen deprivation therapy duration, CRPC PSA level,
      pre-AA PSA level, chemotherapy dosages, duration, and patients progression free
      survival and overall survival after AA treatment were analyzed. Results: Twenty
      three patients (47.9%) achieved PSA decline after deferred CAB. Among total 48
      patients, 24 patients experienced PSA decline more than 50% after AA treatment.
      The median PSA progression-free survival and overall survival after AA treatment
      in the total cohort of 48 patients were 4.4 and 24.3 months, respectively. The
      effective deferred CAB group showed significantly lower PSA level, lower
      percentage of PSA progression, higher total follow-up duration, higher percentage
      of surviving patients, better progression free survival, and overall survival
      estimate after AA treatment. Of the eight variables analyzed, effectiveness in
      deferred CAB showed positive association to progression free survival (HR 0.29,
      95% CI 0.12-0.67, p = 0.004) and overall survival (HR 0.24, 95% CI 0.07-0.81, p =
      0.022). First line androgen deprivation therapy (ADT) duration also showed
      positive association to overall survival (HR 0.95, 95% CI 0.91-0.99, p = 0.023).
      Conclusions: Effectiveness of deferred CAB therapy was positively associated with
      progression free survival and overall survival of AA treatment after docetaxel.
      It can be used as a pre-treatment predictor.

PMID- 29213238
TI  - Electrophysiological and Pharmacological Analyses of Nav1.9 Voltage-Gated Sodium
      Channel by Establishing a Heterologous Expression System.
AB  - Nav1. 9 voltage-gated sodium channel is preferentially expressed in peripheral
      nociceptive neurons. Recent progresses have proved its role in pain sensation,
      but our understanding of Nav1.9, in general, has lagged behind because of
      limitations in heterologous expression in mammal cells. In this work, functional
      expression of human Nav1.9 (hNav1.9) was achieved by fusing GFP to the C-terminal
      of hNav1.9 in ND7/23 cells, which has been proved to be a reliable method to the
      electrophysiological and pharmacological studies of hNav1.9. By using the hNav1.9
      expression system, we investigated the electrophysiological properties of four
      mutations of hNav1.9 (K419N, A582T, A842P, and F1689L), whose
      electrophysiological functions have not been determined yet. The four mutations
      significantly caused positive shift of the steady-state fast inactivation and
      therefore increased hNav1.9 activity, consistent with the phenotype of painful
      peripheral neuropathy. Meanwhile, the effects of inflammatory mediators on
      hNav1.9 were also investigated. Impressively, histamine was found for the first
      time to enhance hNav1.9 activity, indicating its vital role in hNav1.9 modulating
      inflammatory pain. Taken together, our research provided a useful platform for
      hNav1.9 studies and new insight into mechanism of hNav1.9 linking to pain.

PMID- 29213239
TI  - Dynamic Editome of Zebrafish under Aminoglycosides Treatment and Its Potential
      Involvement in Ototoxicity.
AB  - RNA editing is an important co- and post-transcriptional event that generates RNA
      and protein diversity. Aminoglycosides are a group of bactericidal antibiotics
      and a mainstay of antimicrobial therapy for several life-threatening infections.
      However, aminoglycosides can induce ototoxicity, resulting in damage to the
      organs responsible for hearing and balance. At low concentrations,
      aminoglycosides can bind to many RNA sequences and critically influence RNA
      editing. We used a bioinformatics approach to investigate the effect of
      aminoglycosides on global mRNA editing events to gain insight into the
      interactions between mRNA editing and aminoglycoside ototoxicity. We identified
      6,850 mRNA editing sites in protein coding genes in embryonic zebrafish, and in
      about 10% of these, the degree of RNA editing changed more than 15% under
      aminoglycosides treatment. Twelve ear-development or ototoxicity related genes,
      including plekhm1, fgfr1a, sox9a, and calrl2, exhibited remarkable changes in
      mRNA editing levels in zebrafish treated with aminoglycosides. Our results
      indicate that aminoglycosides may have a widespread and complicated influence on
      the progress of mRNA editing and expression. Furthermore, these results highlight
      the potential importance of mRNA editing in the pathogenesis and etiology of
      aminoglycoside-induced ototoxicity.

PMID- 29213240
TI  - Dipeptidyl Peptidase-4 Inhibitors Use and Relative Risk of Ischemic
      Cerebrovascular Disease in Type 2 Diabetic Patients in a Case-Control Study.
AB  - Background and Objectives: Limited research focuses on the risk of ischemic
      cerebrovascular disease associated with use of dipeptidyl peptidase-4 inhibitors
      (DPP-4 inhibitors) in patients with type 2 diabetes mellitus in Taiwan. This
      study aimed to investigate the association between DPP-4 inhibitors use and the
      first episode of ischemic cerebrovascular disease. Methods: We designed a case
      control study using the database of the Taiwan National Health Insurance Program.
      There were 1999 type 2 diabetic subjects aged 20-84 years with the first episode
      of ischemic cerebrovascular disease from 2000 to 2013 as the cases, and 7996 sex-
      and age-matched, randomly selected type 2 diabetic subjects aged 20-84 years
      without any type of cerebrovascular diseases as the matched controls. We
      estimated the odds ratio (OR) and 95% confidence interval (CI) of ischemic
      cerebrovascular disease associated with cumulative duration of DPP-4 inhibitors
      use by the multivariable logistic regression model. Results: After adjustment for
      confounding variables, the adjusted OR of ischemic cerebrovascular disease was
      0.96 (95% CI 0.95, 0.97) in subjects with ever use of DPP-4 inhibitors as
      increase in use duration for every 1 month, compared with never use. The sub
      analysis disclosed that the adjusted ORs of ischemic cerebrovascular disease were
      1.57 (95% CI 1.36, 1.80) for subjects with cumulative duration of DPP-4
      inhibitors use <1 year, and 0.70 (95% CI 0.57, 0.87) for subjects with cumulative
      duration of DPP-4 inhibitors use >=1 year, compared with never use. Conclusion:
      Our findings suggest that DPP-4 inhibitors use correlates with relative risk
      reduction of the first episode of ischemic cerebrovascular disease in type 2
      diabetic patients in a duration-dependent response. The beneficial effect will be
      marked when DPP-4 inhibitors use is >=1 year.

PMID- 29213241
TI  - Interaction of Purinergic P2X4 and P2X7 Receptor Subunits.
AB  - P2X4 and P2X7 are members of the P2X receptor family, comprising seven isoforms
      (P2X1-P2X7) that form homo- and heterotrimeric non-specific cation channels gated
      by extracellular ATP. P2X4 and P2X7 are widely coexpressed, particularly in
      secretory epithelial cells and immune and inflammatory cells, and regulate
      inflammation and nociception. Although functional heteromerization has been
      established for P2X2 and P2X3 subunits expressed in sensory neurons, there are
      contradictory reports regarding a functional interaction between P2X4 and P2X7
      subunits. To resolve this issue, we coexpressed P2X4 and P2X7 receptor subunits
      labeled with green (EGFP) and red (TagRFP) fluorescent proteins in Xenopus laevis
      oocytes and investigated a putative physical interaction between the fusion
      proteins by Forster resonance energy transfer (FRET). Coexpression of P2X4 and
      P2X7 subunits with EGFP and TagRFP located in the extracellular receptor domains
      led to significant FRET signals. Significant FRET signals were also measured
      between C-terminally fluorophore-labeled full-length P2X41-384 and C-terminally
      truncated fluorescent P2X71-408 subunits. We furthermore used the two-electrode
      voltage clamp technique to investigate whether human P2X4 and P2X7 receptors
      (hP2X4, hP2X7) functionally interact at the level of ATP-induced whole-cell
      currents. Concentration-response curves and effects of ivermectin (P2X4
      potentiating drug) or BzATP (P2X7-specific agonist) were consistent with a model
      in which coexpressed hP2X4 and hP2X7 do not interact. Similarly, the effect of
      adding specific inhibitors of P2X4 (PSB-15417) or P2X7 (oATP, A438079) could be
      explained by a model in which only homomers exist, and that these are blocked by
      the respective antagonist. In conclusion, we show that P2X4 and P2X7 subunits can
      form heterotrimeric P2X4/P2X7 receptors. However, unlike observations for P2X2
      and P2X3, coexpression of P2X4 and P2X7 subunits does not result in a novel
      electrophysiologically discriminable P2X receptor phenotype.

PMID- 29213242
TI  - Case-Control Study Examining the Association between Selective Serotonin Reuptake
      Inhibitors Use and Hepatocellular Carcinoma.
AB  - Objectives: The purpose of the study was to assess the relationship between
      selective serotonin reuptake inhibitors use and hepatocellular carcinoma in
      Taiwan. Methods: Using the database of the Taiwan National Health Insurance
      Program, we conducted a case-control study to identify 4901 subjects aged 20
      years and more with newly diagnosed hepatocellular carcinoma in 2000-2013 as the
      cases. We randomly selected 19604 subjects aged 20 years and more without
      hepatocellular carcinoma as the controls. Both cases and controls were matched
      with sex and age. Ever use of selective serotonin reuptake inhibitors was defined
      as a subject who had at least a prescription for selective serotonin reuptake
      inhibitors before index date. Never use was defined as a subject who never had a
      prescription for selective serotonin reuptake inhibitors before index date. The
      odds ratio (OR) and 95% confidence interval (CI) for hepatocellular carcinoma
      associated with selective serotonin reuptake inhibitors use was estimated by the
      multivariable logistic regression model. Results: Among subjects with any one of
      the comorbid conditions associated with hepatocellular carcinoma, the adjusted OR
      of hepatocellular carcinoma was 0.89 (95% CI 0.75, 1.06) for subjects with ever
      use of selective serotonin reuptake inhibitors, comparing with never use.
      Conclusion: The findings indicate that among subjects with any one of the
      comorbid conditions associated with hepatocellular carcinoma, no significant
      association can be detected between selective serotonin reuptake inhibitors use
      and hepatocellular carcinoma.

PMID- 29213243
TI  - Mechanism of Chinese Medicine Herbs Effects on Chronic Heart Failure Based on
      Metabolic Profiling.
AB  - Chronic heart failure (CHF) is a major public health problem in huge population
      worldwide. The detailed understanding of CHF mechanism is still limited. Zheng
      (syndrome) is the criterion of diagnosis and therapeutic in Traditional Chinese
      Medicine (TCM). Syndrome prediction may be a better approach for understanding of
      CHF mechanism basis and its treatment. The authors studied disturbed metabolic
      biomarkers to construct a predicting mode to assess the diagnostic value of
      different syndrome of CHF and explore the Chinese herbal medicine (CHM) efficacy
      on CHF patients. A cohort of 110 patients from 11 independent centers was studied
      and all patients were divided into 3 groups according to TCM syndrome
      differentiation: group of Qi deficiency syndrome, group of Qi deficiency and
      Blood stasis syndrome, and group of Qi deficiency and Blood stasis and Water
      retention syndrome. Plasma metabolomic profiles were determined by UPLC-TOF/MS
      and analyzed by multivariate statistics. About 6 representative metabolites were
      highly possible to be associated with CHF, 4, 7, and 5 metabolites with Qi
      deficiency syndrome, Qi deficiency and Blood stasis syndrome, and Qi deficiency
      and Blood stasis and Water retention syndrome (VIP > 1, p < 0.05). The diagnostic
      model was further constructed based on the metabolites to diagnose other CHF
      patients with satisfying sensitivity and specificity (sensitivity and specificity
      are 97.1 and 80.6% for CHF group vs. NH group; 97.1 and 80.0% for QD group vs. NH
      group; 97.1 and 79.5% for QB group vs. NH group; 97.1 and 88.9% for QBW group vs.
      NH group), validating the robustness of plasma metabolic profiling to diagnostic
      strategy. By comparison of the metabolic profiles, 9 biomarkers, 2
      arachidonoylglycerophosphocholine, LysoPE 16:0, PS 21:0, LysoPE 20:4, LysoPE
      18:0, linoleic acid, LysoPE 18:2, 4-hydroxybenzenesulfonic acid, and LysoPE 22:6,
      may be especially for the effect of CHM granules. A predicting model was
      attempted to construct and predict patient based on the related symptoms of CHF
      and the potential biomarkers regulated by CHM were explored. This trial was
      registered with NCT01939236 (https://clinicaltrials.gov/).

PMID- 29213244
TI  - Virus-Infected Plants Altered the Host Selection of Encarsia formosa, a
      Parasitoid of Whiteflies.
AB  - The sweetpotato whitefly Bemisia tabaci (Gennadius) is one of the most invasive
      pest species worldwide. Q and B biotypes are the two most devastating species
      within the B. tabaci complex. Bemisia tabaci can vector hundreds of plant viruses
      that seriously threaten crop production. Endoparasitoid, Encarsia formosa Gahan,
      is widely used to control whiteflies, however, little is known about the effects
      of virus-infected plants on E. formosa parasitism of B. tabaci. Here, we reported
      that tomato, which was infected with Tomato Yellow Leaf Curl Virus (TYLCV),
      altered the host selection of E. formosa between B. tabaci Q and B biotypes. On
      healthy tomato plants, parasitism and host selection by E. formosa did not differ
      between the 3rd-instar nymphs of B. tabaci Q and B biotypes. On TYLCV-infected
      tomato plants, however, B. tabaci Q biotype were significantly more attractive to
      E. formosa than B biotype. When TYLCV-infected tomato plants were infested with
      B. tabaci Q or B biotype, volatile profiles differed quantitatively but not
      qualitatively. Olfactometer assays suggested that the preference of E. formosa to
      Q over B biotype was associated with an elevated level of beta-Myrcene, beta
      Ocimene, beta-Caryophyllene, and alpha-Humulene from TYLCV-infected tomato
      plants.

PMID- 29213246
TI  - The Influence of Footwear on the Modular Organization of Running.
AB  - For most of our history, we predominantly ran barefoot or in minimalist shoes.
      The advent of modern footwear, however, might have introduced alterations in the
      motor control of running. The present study investigated shod and barefoot
      running under the perspective of the modular organization of muscle activation,
      in order to help addressing the neurophysiological factors underlying human
      locomotion. On a treadmill, 20 young and healthy inexperienced barefoot runners
      ran shod and barefoot at preferred speed (2.8 +/- 0.4 m/s). Fundamental
      synergies, containing the time-dependent activation coefficients (motor
      primitives) and the time-invariant muscle weightings (motor modules), were
      extracted from 24 ipsilateral electromyographic activities using non-negative
      matrix factorization. In shod running, the average foot strike pattern was a
      rearfoot strike, while in barefoot running it was a mid-forefoot strike. In both
      conditions, five fundamental synergies were enough to describe as many gait cycle
      phases: weight acceptance, propulsion, arm swing, early swing and late swing. We
      found the motor primitives to be generally shifted earlier in time during the
      stance-related phases and later in the swing-related ones in barefoot running.
      The motor primitive describing the propulsion phase was significantly of shorter
      duration (peculiarity confirmed by the analysis of the spinal motor output). The
      arm swing primitive, instead, was significantly wider in the barefoot condition.
      The motor modules demonstrated analogous organization with some significant
      differences in the propulsion, arm swing and late swing synergies. Other than to
      the trivial absence of shoes, the differences might be deputed to the lower ankle
      gear ratio (and the consequent increased system instability) and to the higher
      recoil capabilities of the longitudinal foot arch during barefoot compared to
      shod running.

PMID- 29213247
TI  - Mediating Effects of Global Negative Effect Expectancies on the Association
      between Problematic Cannabis Use and Social Anxiety.
AB  - The relationship between social anxiety (SA) and cannabis use among adolescents
      and young adults is a highly debated topic. In this cross-sectional study, we
      tested whether cannabis use expectancies mediated the association between SA and
      cannabis use severity in a sample of 343 young adults (74.3% male) who used
      cannabis. They completed self-report measures for the screening of problematic
      cannabis use (Cannabis Use Problems Identification Test) and SA symptoms (Social
      Interaction Anxiety Scale and Social Phobia Scale). A multiple mediation analysis
      was used to test whether marijuana effect expectancies mediate SA effect on
      problematic cannabis use. SA was negatively associated with cannabis use severity
      in this sample, and we found evidence that cannabis use expectancies fully
      mediated this relationship. Specifically, global negative effect expectancies
      influence the relationship between SA and problematic cannabis use. These
      findings may inform current prevention strategies and clinical intervention for
      young adults who use cannabis.

PMID- 29213245
TI  - Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in
      Vascular Inflammation in Zucker Rats and Evolution with Aging.
AB  - Background: The metabolic syndrome (MetS) and aging are associated with
      modifications in blood coagulation factors, vascular inflammation, and increased
      risk of thrombosis. Objectives: Our aim was to determine concomitant changes in
      thrombin generation in the blood compartment and at the surface of vascular
      smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids
      (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of
      the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at
      25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated
      thrombography (CAT). Results: Endogenous thrombin potential (ETP) was increased
      in obese rats independent of platelets and age. Clot half-lysis time was delayed
      with obesity and age. Interleukin (IL)-1beta and IL-13 were increased with
      obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic,
      or palmitic acid increased thrombin generation in plasma whereas adiponectin had
      an opposite effect. ETP was increased at the surface of VSMCs from obese rats and
      addition of exogenous palmitic acid further enhanced ETP values. Gelatinase
      activity was increased in aorta at both ages in obese rats and MMP-2 activity was
      increased in VSMCs from obese rats. Conclusions: Our study demonstrated in MetS
      an early prothrombotic phenotype of the blood compartment reinforced by
      procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms
      involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased
      saturated fatty acids responsible for additive procoagulant effects. Whether
      specifically targeting this hypercoagulability using direct thrombin inhibitors
      would improve outcome in MetS is worth investigating.

PMID- 29213248
TI  - Impact of Diglossia on Word and Non-word Repetition among Language Impaired and
      Typically Developing Arabic Native Speaking Children.
AB  - The study tested the impact of the phonological and lexical distance between a
      dialect of Palestinian Arabic spoken in the north of Israel (SpA) and Modern
      Standard Arabic (StA or MSA) on word and non-word repetition in children with
      specific language impairment (SLI) and in typically developing (TD) age-matched
      controls. Fifty kindergarten children (25 SLI, 25 TD; mean age 5;5) and fifty
      first grade children (25 SLI, 25 TD; mean age 6:11) were tested with a repetition
      task for 1-4 syllable long real words and pseudo words; Items varied
      systematically in whether each encoded a novel StA phoneme or not, namely a
      phoneme that is only used in StA but not in the spoken dialect targeted. Real
      words also varied in whether they were lexically novel, meaning whether the word
      is used only in StA, but not in SpA. SLI children were found to significantly
      underperform TD children on all repetition tasks indicating a general
      phonological memory deficit. More interesting for the current investigation is
      the observed strong and consistent effect of phonological novelty on word and non
      word repetition in SLI and TD children, with a stronger effect observed in SLI.
      In contrast with phonological novelty, the effect of lexical novelty on word
      repetition was limited and it did not interact with group. The results are argued
      to reflect the role of linguistic distance in phonological memory for novel
      linguistic units in Arabic SLI and, hence, to support a specific Linguistic
      Distance Hypothesis of SLI in a diglossic setting. The implications of the
      findings for assessment, diagnosis and intervention with Arabic speaking children
      with SLI are discussed.

PMID- 29213249
TI  - Skewed Sociolinguistic Awareness of a Native Non-standard Dialect: Evidence from
      the Cypriot Greek Writing of Greek Cypriot Students.
AB  - Over the last 50 years, sociolinguistic research in settings in which a regional,
      social, or ethnic non-standard linguistic variety is used alongside the standard
      variety of the same language has steadily increased. The educational implications
      of the concomitant use of such varieties have also received a great deal of
      research attention. This study deals with regional linguistic variation and its
      implications for education by focusing on the Greek Cypriot educational context.
      This context is ideal for investigating the linguistic profiles of speakers of
      proximal varieties as the majority of Greek Cypriots are primarily educated in
      just one of their varieties: the standard educational variety. The aim of our
      study was to understand Greek Cypriot primary school pupils' sociolinguistic
      awareness via examination of their written production in their home variety
      [Cypriot Greek (CG) dialect]. Our assumption was that, because written production
      is less spontaneous than speech, it better reflects pupils' conscious awareness.
      Pupils were advised to produce texts that reflected their everyday language with
      family and friends (beyond school boundaries). As expected, students' texts
      included an abundance of mesolectal features and the following were the ten most
      frequent: (1) palato-alveolar consonants, (2) future particle [ena] and
      conditional [itan na] + subjunctive, (3) consonant devoicing, (4) CG-specific
      verb stems, (5) final [n] retention, (6) [en/ eni] instead of [ine], (7) CG
      specific verb endings, (8) [en/e] instead of [den], (9) elision of intervocalic
      fricative [gamma], and (10) CG-specific adverbs. Importantly, in addition to the
      expected mesolectal features that reflect contemporary CG, students included a
      significant and unexpected number of basilectal features and instances of
      hyperdialectism (that are not representative of today's linguistic reality) which
      rendered their texts register-inappropriate. This led us to conclude that Greek
      Cypriot students have a skewed sociolinguistic awareness of variation within
      their first dialect and a distorted impression of their own everyday language. We
      argue that the portrayal of CG in its basilectal form was performed intentionally
      by students in an effort to distance themselves from a socially constructed
      identity of a rural, uneducated, and stigmatized non-standard-dialect speaker.
      The study is of international relevance as it deals with sociolinguistic issues
      that pertain to all bidialectal speakers.

PMID- 29213250
TI  - Why Prediction Matters in Multitasking and How Predictability Can Improve It.

PMID- 29213251
TI  - Who Wants to Be an Intrapreneur? Relations between Employees' Entrepreneurial,
      Professional, and Leadership Career Motivations and Intrapreneurial Motivation in
      Organizations.
AB  - This paper reports an empirical study conducted to examine the relationship
      between employees' Entrepreneurial, Professional, and Leadership (EPL) career
      motivations and their intrapreneurial motivation. Using data collected from 425
      working adults in the research/innovation and healthcare settings, we develop a
      self-report measure of employee intrapreneurial motivation. We also adapt an
      existing self-report measure of E, P, and L career motivations (previously
      developed and used with university students) for use with working adult
      organizational employees. Confirmatory factor analysis indicate that E, P, and L
      motivations and intrapreneurial motivation can be measured independently and
      reliably, while regression analyses show that the employees' E, P, and L
      motivations all contribute to explaining variance in their intrapreneurial
      motivation. Individuals with high E, P, and L motivational profiles are also
      found to have the highest intrapreneurial motivation scores, while those low on
      E, P, and L motivations have the least intrapreneurial motivation. Our findings
      suggest that the potential for intrapreneurship is not unique to only
      entrepreneurial employees. Instead, one can find intrapreneurs among employees
      with strong leadership and professional motivations as well. We discuss the
      findings in the context of generating more research to address the challenges of
      talent management in the 21st century knowledge economies where there is greater
      career mobility and boundarylessness in the workforce.

PMID- 29213252
TI  - Hemispheric Asymmetries in Price Estimation: Do Brain Hemispheres Attribute
      Different Monetary Values?
AB  - The Spatial Numerical Association of Response Codes (SNARC) effect has been
      associated with a wide range of magnitude processing. This effect is due to an
      implicit relationship between numbers and horizontal space, according to which
      weaker magnitudes and smaller numbers are represented on the left, whereas
      stronger magnitudes and larger numbers are represented on the right. However, for
      some particular type of magnitudes such as price, judgments may be also
      influenced by perceived quality and thus involving valence attribution biases
      driven by brain asymmetries. In the present study, a lateralized tachistoscopic
      presentation was used in a price estimation task, using a weight estimation task
      as a control, to assess differences in asymmetries between these two attributes.
      Results show a side bias in the former condition but not in the latter, thus
      indicating that other non-numerical mechanisms are involved in price estimation.
      Specifically, prices were estimated lower in the left visual field than in the
      right visual field. The proposed explanation is that price appraisal might
      involve a valence attribution mechanism leading to a better perceived quality
      (related to higher prices) when objects are processed primarily in the left
      hemisphere, and to a lower perceived quality (related to lower prices) when
      objects are processed primarily in the right hemisphere.

PMID- 29213253
TI  - The Role of Slow Wave Sleep in Memory Pathophysiology: Focus on Post-traumatic
      Stress Disorder and Eye Movement Desensitization and Reprocessing.

PMID- 29213254
TI  - Blue-Light Therapy following Mild Traumatic Brain Injury: Effects on White Matter
      Water Diffusion in the Brain.
AB  - Mild traumatic brain injury (mTBI) is a common and often inconspicuous wound that
      is frequently associated with chronic low-grade symptoms and cognitive
      dysfunction. Previous evidence suggests that daily blue wavelength light therapy
      may be effective at reducing fatigue and improving sleep in patients recovering
      from mTBI. However, the effects of light therapy on recovering brain structure
      remain unexplored. In this study, we analyzed white matter diffusion properties,
      including generalized fractional anisotropy, and the quantity of water diffusion
      in isotropic (i.e., isotropic diffusion) and anisotropic fashion (i.e.,
      quantitative anisotropy, QA) for fibers crossing 11 brain areas known to be
      significantly affected following mTBI. Specifically, we investigated how 6 weeks
      of daily morning blue light exposure therapy (compared to an amber-light placebo
      condition) impacted changes in white matter diffusion in individuals with mTBI.
      We observed a significant impact of the blue light treatment (relative to the
      placebo) on the amount of water diffusion (QA) for multiple brain areas,
      including the corpus callosum, anterior corona radiata, and thalamus. Moreover,
      many of these changes were associated with improvements in sleep latency and
      delayed memory. These findings suggest that blue wavelength light exposure may
      serve as one of the potential non-pharmacological treatments for facilitating
      structural and functional recovery following mTBI; they also support the use of
      QA as a reliable neuro-biomarker for mTBI therapies.

PMID- 29213255
TI  - Evaluating Monitoring Strategies to Detect Precipitation-Induced Microbial
      Contamination Events in Karstic Springs Used for Drinking Water.
AB  - Monitoring of microbial drinking water quality is a key component for ensuring
      safety and understanding risk, but conventional monitoring strategies are
      typically based on low sampling frequencies (e.g., quarterly or monthly). This is
      of concern because many drinking water sources, such as karstic springs are often
      subject to changes in bacterial concentrations on much shorter time scales (e.g.,
      hours to days), for example after precipitation events. Microbial contamination
      events are crucial from a risk assessment perspective and should therefore be
      targeted by monitoring strategies to establish both the frequency of their
      occurrence and the magnitude of bacterial peak concentrations. In this study we
      used monitoring data from two specific karstic springs. We assessed the
      performance of conventional monitoring based on historical records and tested a
      number of alternative strategies based on a high-resolution data set of bacterial
      concentrations in spring water collected with online flow cytometry (FCM). We
      quantified the effect of increasing sampling frequency and found that for the
      specific case studied, at least bi-weekly sampling would be needed to detect
      precipitation events with a probability of >90%. We then proposed an optimized
      monitoring strategy with three targeted samples per event, triggered by
      precipitation measurements. This approach is more effective and efficient than
      simply increasing overall sampling frequency. It would enable the water utility
      to (1) analyze any relevant event and (2) limit median underestimation of peak
      concentrations to approximately 10%. We conclude with a generalized perspective
      on sampling optimization and argue that the assessment of short-term dynamics
      causing microbial peak loads initially requires increased sampling/analysis
      efforts, but can be optimized subsequently to account for limited resources. This
      offers water utilities and public health authorities systematic ways to evaluate
      and optimize their current monitoring strategies.

PMID- 29213256
TI  - Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic
      Consortium.
AB  - Bacterial endosymbionts and their insect hosts establish an intimate metabolic
      relationship. Bacteria offer a variety of essential nutrients to their hosts,
      whereas insect cells provide the necessary sources of matter and energy to their
      tiny metabolic allies. These nutritional complementations sustain themselves on a
      diversity of metabolite exchanges between the cell host and the reduced yet
      highly specialized bacterial metabolism-which, for instance, overproduces a small
      set of essential amino acids and vitamins. A well-known case of metabolic
      complementation is provided by the cedar aphid Cinara cedri that harbors two co
      primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc,
      and in which some metabolic pathways are partitioned between different partners.
      Here we present a genome-scale metabolic network (GEM) for the bacterial
      consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the
      confirmation of cases of metabolic complementation previously described by genome
      analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an
      event of metabolic pathway sharing between the two endosymbionts, namely the
      biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc
      showed that the consortium metabolism is a highly integrated yet fragile network.
      We also have explored the evolutionary pathways leading to the emergence of
      metabolic complementation between reduced metabolisms starting from individual,
      complete networks. Our results suggest that, during the establishment of
      metabolic complementation in endosymbionts, adaptive evolution is significant in
      the case of tryptophan biosynthesis, whereas vitamin production pathways seem to
      adopt suboptimal solutions.

PMID- 29213257
TI  - Bacterial Community Dynamics in Dichloromethane-Contaminated Groundwater
      Undergoing Natural Attenuation.
AB  - The uncontrolled release of the industrial solvent methylene chloride, also known
      as dichloromethane (DCM), has resulted in widespread groundwater contamination in
      the United States. Here we investigate the role of groundwater bacterial
      communities in the natural attenuation of DCM at an undisclosed manufacturing
      site in New Jersey. This study investigates the bacterial community structure of
      groundwater samples differentially contaminated with DCM to better understand the
      biodegradation potential of these autochthonous bacterial communities. Bacterial
      community analysis was completed using high-throughput sequencing of the 16S rRNA
      gene of groundwater samples (n = 26) with DCM contamination ranging from 0.89 to
      9,800,000 MUg/L. Significant DCM concentration-driven shifts in overall bacterial
      community structure were identified between samples, including an increase in the
      abundance of Firmicutes within the most contaminated samples. Across all samples,
      a total of 6,134 unique operational taxonomic units (OTUs) were identified, with
      16 taxa having strong correlations with increased DCM concentration. Putative DCM
      degraders such as Pseudomonas, Dehalobacterium and Desulfovibrio were present
      within groundwater across all levels of DCM contamination. Interestingly, each of
      these taxa dominated specific DCM contamination ranges respectively. Potential
      DCM degrading lineages yet to be cited specifically as a DCM degrading organisms,
      such as the Desulfosporosinus, thrived within the most heavily contaminated
      groundwater samples. Co-occurrence network analysis revealed aerobic and
      anaerobic bacterial taxa with DCM-degrading potential were present at the study
      site. Our 16S rRNA gene survey serves as the first in situ bacterial community
      assessment of contaminated groundwater harboring DCM concentrations ranging over
      seven orders of magnitude. Diversity analyses revealed known as well as
      potentially novel DCM degrading taxa within defined DCM concentration ranges,
      indicating niche-specific responses of these autochthonous populations.
      Altogether, our findings suggest that monitored natural attenuation is an
      appropriate remediation strategy for DCM contamination, and that high-throughput
      sequencing technologies are a robust method for assessing the potential role of
      biodegrading bacterial assemblages in the apparent reduction of DCM
      concentrations in environmental scenarios.

PMID- 29213258
TI  - The Complexity of Antibody Responses Elicited against the Respiratory Syncytial
      Virus Glycoproteins in Hospitalized Children Younger than 2 Years.
AB  - The influence of age and maternal antibodies on the antibody responses to human
      respiratory syncytial virus (hRSV) glycoproteins in very young children has been
      a matter of controversy. Both, immaturity of the immune system at very early age
      and suppression of the host immune response by high level of maternal antibodies
      have been claimed to limit the host antibody response to virus infection and to
      jeopardize the use of hRSV vaccines under development in that age group. Hence,
      the antibody responses to the two major hRSV glycoproteins (F and G) were
      evaluated in children younger than 2 years, hospitalized with laboratory
      confirmed hRSV bronchiolitis. A strong negative correlation was found between the
      titre of circulating ELISA antibodies directed against either prefusion or
      postfusion F in the acute phase, but not age, and their fold change at
      convalescence. These changes correlated also with the level of circulating
      neutralizing antibodies in sera. As reported in adults, most neutralizing
      antibodies in a subset of tested sera could not be depleted with postfusion F,
      suggesting that they were mostly directed against prefusion-specific epitopes. In
      contrast, a weak negative association was found for group-specific anti-G
      antibodies in the acute phase and their fold change at convalescence only after
      correcting for the antigenic group of the infecting virus. In addition, large
      discrepancies were observed in some individuals between the antibody responses
      specific for F and G glycoproteins. These results illustrate the complexity of
      the anti-hRSV antibody responses in children experiencing a primary severe
      infection and the influence of preexisting maternal antibodies on the host
      response, factors that should influence hRSV serological studies as well as
      vaccine development.

PMID- 29213259
TI  - Characterization of a Suppressive Cis-acting Element in the Epstein-Barr Virus
      LMP1 Promoter.
AB  - Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein-Barr
      virus (EBV) and is essential for immortalization of B cells by the virus.
      Previous studies suggested that several transcription factors, such as PU.1, RBP
      Jkappa, NFkappaB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however,
      the means by which the oncogene is negatively regulated remains unclear. Here, we
      introduced short mutations into the proximal LMP1 promoter that includes
      recognition sites for the E-box and Ikaros transcription factors in the context
      of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited
      increased LMP1 expression and EBV-mediated immortalization of B cells. However,
      single mutations of either the E-box or Ikaros sites had limited effects on LMP1
      expression and transformation. Our results suggest that this region contains a
      suppressive cis-regulatory element, but other transcriptional repressors (apart
      from the E-box and Ikaros transcription factors) may remain to be discovered.

PMID- 29213260
TI  - Increased Denitrification Rates Associated with Shifts in Prokaryotic Community
      Composition Caused by Varying Hydrologic Connectivity.
AB  - While modern developments in agriculture have allowed for increases in crop
      yields and rapid human population growth, they have also drastically altered
      biogeochemical cycles, including the biotransformation of nitrogen.
      Denitrification is a critical process performed by bacteria and fungi that
      removes nitrate in surface waters, thereby serving as a potential natural
      remediation strategy. We previously reported that constant inundation resulted in
      a coupling of denitrification gene abundances with denitrification rates in
      sediments, but these relationships were not maintained in periodically-inundated
      or non-inundated environments. In this study, we utilized Illumina next
      generation sequencing to further evaluate how the microbial community responds to
      these hydrologic regimes and how this community is related to denitrification
      rates at three sites along a creek in an agricultural watershed over 2 years. The
      hydrologic connectivity of the sampling location had a significantly greater
      influence on the denitrification rate (P = 0.010), denitrification gene
      abundances (P < 0.001), and the prokaryotic community (P < 0.001), than did other
      spatiotemporal factors (e.g., creek sample site or sample month) within the same
      year. However, annual variability among denitrification rates was also observed
      (P < 0.001). Furthermore, the denitrification rate was significantly positively
      correlated with water nitrate concentration (Spearman's rho = 0.56, P < 0.0001),
      denitrification gene abundances (rho = 0.23-0.47, P <= 0.006), and the abundances
      of members of the families Burkholderiaceae, Anaerolinaceae, Microbacteriaceae,
      Acidimicrobineae incertae sedis, Cytophagaceae, and Hyphomicrobiaceae (rho = 0.17
      0.25, P <= 0.041). Prokaryotic community composition accounted for the least
      amount of variation in denitrification rates (22%), while the collective
      influence of spatiotemporal factors and gene abundances accounted for 37%, with
      40% of the variation related to interactions among all parameters. Results of
      this study suggest that the hydrologic connectivity at each location had a
      greater effect on the prokaryotic community than did spatiotemporal differences,
      where inundation is associated with shifts favoring increased denitrification
      potential. We further establish that while complex interactions among the
      prokaryotic community influence denitrification, the link between hydrologic
      connectivity, microbial community composition, and genetic potential for
      biogeochemical cycling is a promising avenue to explore hydrologic remediation
      strategies such as periodic flooding.

PMID- 29213261
TI  - Antibiotic-Induced Alterations in Gut Microbiota Are Associated with Changes in
      Glucose Metabolism in Healthy Mice.
AB  - The gut microbiome plays an important role in health and disease. Antibiotics are
      known to alter gut microbiota, yet their effects on glucose tolerance in lean,
      normoglycemic mice have not been widely investigated. In this study, we aimed to
      explore mechanisms by which treatment of lean mice with antibiotics (ampicillin,
      metronidazole, neomycin, vancomycin, or their cocktail) influences the microbiome
      and glucose metabolism. Specifically, we sought to: (i) study the effects on body
      weight, fasting glucose, glucose tolerance, and fasting insulin, (ii) examine the
      changes in expression of key genes of the bile acid and glucose metabolic
      pathways in the liver and ileum, (iii) identify the shifts in the cecal
      microbiota, and (iv) infer interactions between gene expression, microbiome, and
      the metabolic parameters. Treatment with individual or a cocktail of antibiotics
      reduced fasting glucose but did not affect body weight. Glucose tolerance changed
      upon treatment with cocktail, ampicillin, or vancomycin as indicated by reduced
      area under the curve of the glucose tolerance test. Antibiotic treatment changed
      gene expression in the ileum and liver, and shifted the alpha and beta
      diversities of gut microbiota. Network analyses revealed associations between
      Akkermansia muciniphila with fasting glucose and liver farsenoid X receptor (Fxr)
      in the top ranked host-microbial interactions, suggesting possible mechanisms by
      which this bacterium can mediate systemic changes in glucose metabolism. We
      observed Bacteroides uniformis to be positively and negatively correlated with
      hepatic Fxr and Glucose 6-phosphatase, respectively. Overall, our transkingdom
      network approach is a useful hypothesis generating strategy that offers insights
      into mechanisms by which antibiotics can regulate glucose tolerance in non-obese
      healthy animals. Experimental validation of our predicted microbe-phenotype
      interactions can help identify mechanisms by which antibiotics affect host
      phenotypes and gut microbiota.

PMID- 29213262
TI  - The Oxidative Stress Agent Hypochlorite Stimulates c-di-GMP Synthesis and Biofilm
      Formation in Pseudomonas aeruginosa.
AB  - The opportunistic human pathogen Pseudomonas aeruginosa is able to survive under
      a variety of often harmful environmental conditions due to a multitude of
      intrinsic and adaptive resistance mechanisms, including biofilm formation as one
      important survival strategy. Here, we investigated the adaptation of P.
      aeruginosa PAO1 to hypochlorite (HClO), a phagocyte-derived host defense compound
      and frequently used disinfectant. In static biofilm assays, we observed a
      significant enhancement in initial cell attachment in the presence of sublethal
      HClO concentrations. Subsequent LC-MS analyses revealed a strong increase in
      cyclic-di-GMP (c-di-GMP) levels suggesting a key role of this second messenger in
      HClO-induced biofilm development. Using DNA microarrays, we identified a 26-fold
      upregulation of ORF PA3177 coding for a putative diguanylate cyclase (DGC), which
      catalyzes the synthesis of the second messenger c-di-GMP - an important regulator
      of bacterial motility, sessility and persistence. This DGC PA3177 was further
      characterized in more detail demonstrating its impact on P. aeruginosa motility
      and biofilm formation. In addition, cell culture assays attested a role for
      PA3177 in the response of P. aeruginosa to human phagocytes. Using a subset of
      different mutants, we were able to show that both Pel and Psl exopolysaccharides
      are effectors in the PA3177-dependent c-di-GMP network.

PMID- 29213263
TI  - Scoring Targets of Transcription in Bacteria Rather than Focusing on Individual
      Binding Sites.
AB  - Reliable identification of targets of bacterial regulators is necessary to
      understand bacterial gene expression regulation. These targets are commonly
      predicted by searching for high-scoring binding sites in the upstream genomic
      regions, which typically leads to a large number of false positives. In contrast
      to the common approach, here we propose a novel concept, where overrepresentation
      of the scoring distribution that corresponds to the entire searched region is
      assessed, as opposed to predicting individual binding sites. We explore two
      implementations of this concept, based on Kolmogorov-Smirnov (KS) and Anderson
      Darling (AD) tests, which both provide straightforward P-value estimates for
      predicted targets. This approach is implemented for pleiotropic bacterial
      regulators, including sigma70 (bacterial housekeeping sigma factor) target
      predictions, which is a classical bioinformatics problem characterized by low
      specificity. We show that KS based approach is both faster and more accurate,
      departing from the current paradigm of AD being slower, but more accurate.
      Moreover, KS approach leads to a significant increase in the search accuracy
      compared to the standard approach, while at the same time straightforwardly
      assigning well established P-values to each potential target. Consequently, the
      new KS based method proposed here, which assigns P-values to fixed length
      upstream regions, provides a fast and accurate approach for predicting bacterial
      transcription targets.

PMID- 29213264
TI  - A Novel Halotolerant Thermoalkaliphilic Esterase from Marine Bacterium
      Erythrobacter seohaensis SW-135.
AB  - A novel esterase gene, e69, was cloned from Erythrobacter seohaensis SW-135,
      which was isolated from a tidal flat sediment of the Yellow Sea in Korea. This
      gene is 825 bp in length and codes for a 29.54 kDa protein containing 274 amino
      acids. Phylogenetic analysis showed that E69 is a new member of the bacterial
      lipolytic enzyme family IV. This enzyme exhibited the highest level of activity
      toward p-nitrophenyl (NP) butyrate but little or no activity toward the other p
      NP esters tested. The optimum temperature and pH of the catalytic activity of E69
      were 60 degrees C and pH 10.5, respectively. The enzyme exhibited stable activity
      over a wide range of alkaline pH values (7.5-9.5). In addition, E69 was found to
      be a halotolerant esterase as it exhibited the highest hydrolytic activity in the
      presence of 0.5 M NaCl and was still active in the presence of 3 M NaCl.
      Moreover, it possessed some degree of tolerance to Triton X-100 and several
      organic solvents. Through homology modeling and comparison with other esterases,
      it was suggested that the absence of the cap domain and its narrow substrate
      binding pocket might be responsible for its narrow substrate specificity.
      Sequence and structural analysis results suggested that its high ratio of
      negatively to positively charged residues, large hydrophobic surface area, and
      negative electrostatic potential on the surface may be responsible for its
      alkaline adaptation. The results of this study provide insight into marine
      alkaliphilic esterases, and the unique properties of E69 make it a promising
      candidate as a biocatalyst for industrial applications.

PMID- 29213265
TI  - Lactobacillus plantarum MYS6 Ameliorates Fumonisin B1-Induced Hepatorenal Damage
      in Broilers.
AB  - Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species is a predominant
      Group 2B carcinogen occurring in maize and maize-based poultry feeds. It is shown
      to be nephrotoxic, hepatotoxic, neurotoxic, and immunosuppressing in animals. In
      this study, we report the ameliorating effects of a probiotic strain,
      Lactobacillus plantarum MYS6 on FB1-induced toxicity and oxidative damage in
      broilers. A 6-week dietary experiment consisting of 48 broilers was performed in
      six treatment groups. Probiotic treatment (109 cells/mL) involved pre
      colonization of broilers with L. plantarum MYS6 while co-administration treatment
      involved supplementation of probiotic and FB1-contaminated diet (200 mg/Kg feed)
      simultaneously. At the end of the treatment period, growth performance,
      hematology, serum biochemistry, and markers of oxidative stress in serum and
      tissue homogenates were evaluated in all the broilers. The histopathological
      changes in hepatic and renal tissues were further studied. The results
      demonstrated that administration of L. plantarum MYS6 efficiently improved the
      feed intake, body weight and feed conversion ratio in broilers. It mitigated the
      altered levels of hematological indices such as complete blood count, hemoglobin,
      and hematocrit. Serum parameters such as serum glutamic oxaloacetic transaminase,
      serum glutamic pyruvic transaminase, creatinine, cholesterol, triglycerides, and
      albumin were significantly restored after administering the probiotic in FB1
      intoxicated broilers. Additionally, L. plantarum MYS6 alleviated the levels of
      oxidative stress markers in serum and tissue homogenate of liver. The
      histopathological data of liver and kidney further substantiated the overall
      protection offered by L. plantarum MYS6 against FB1-induced cellular toxicity and
      organ damage in broilers. Our results indicated that co-administration of
      probiotic along with the toxin had better effect in detoxification compared to
      its pre-colonization in broilers. Collectively, our study signifies the
      protective role of L. plantarum MYS6 in ameliorating the FB1-induced toxicity in
      the vital organs and subsequent oxidative stress in broilers. The probiotic L.
      plantarum MYS6 can further be formulated into a functional feed owing to its anti
      fumonisin attributes and role in mitigating FB1-induced hepatorenal damage.

PMID- 29213266
TI  - Taxonomic and Functional Differences between Microbial Communities in Qinghai
      Lake and Its Input Streams.
AB  - Understanding microbial communities in terms of taxon and function is essential
      to decipher the biogeochemical cycling in aquatic ecosystems. Lakes and their
      input streams are highly linked. However, the differences between microbial
      assemblages in streams and lakes are still unclear. In this study, we conducted
      an intensive field sampling of microbial communities from lake water and stream
      biofilms in the Qinghai Lake watershed, the largest lake in China. We determined
      bacterial communities using high-throughput 16S rRNA gene sequencing and
      predicted functional profiles using PICRUSt to determine the taxonomic and
      functional differences between microbial communities in stream biofilms and lake
      water. The results showed that stream biofilms and lake water harbored distinct
      microbial communities. The microbial communities were different taxonomically and
      functionally between stream and lake. Moreover, streams biofilms had a microbial
      network with higher connectivity and modularity than lake water. Functional beta
      diversity was strongly correlated with taxonomic beta diversity in both the
      stream and lake microbial communities. Lake microbial assemblages displayed
      greater predicted metabolic potentials of many metabolism pathways while the
      microbial assemblages in stream biofilms were more abundant in xenobiotic
      biodegradation and metabolism and lipid metabolism. Furthermore, lake microbial
      assemblages had stronger predicted metabolic potentials in amino acid metabolism,
      carbon fixation, and photosynthesis while stream microbial assemblages were
      higher in carbohydrate metabolism, oxidative phosphorylation, and nitrogen
      metabolism. This study adds to our knowledge of stream-lake linkages from the
      functional and taxonomic composition of microbial assemblages.

PMID- 29213267
TI  - Revealing the Complexity in CD8 T Cell Responses to Infection in Inbred C57B/6
      versus Outbred Swiss Mice.
AB  - Recent work has suggested that current mouse models may underrepresent the
      complexity of human immune responses. While most mouse immunology studies utilize
      inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be
      extended to all mouse strains or generalized to humans. We recently described a
      "surrogate activation marker" approach that could be used to track polyclonal CD8
      T cell responses in inbred and outbred mice and noted substantial discord in the
      magnitude and kinetics of CD8 T cell responses in individual outbred mice
      following infection. However, how the memory CD8 T cell response develops
      following infection and the correlates of memory CD8 T cell-mediated protection
      against re-infection in outbred mice remains unknown. In this study, we
      investigated development of pathogen-specific memory CD8 T cell responses in
      inbred C57B/6 and outbred National Institutes of Health Swiss mice following
      lymphocytic choriomeningitis virus or L. monocytogenes infection. Interestingly,
      the size of the memory CD8 T cell pool generated and rate of phenotypic
      progression was considerably more variable in individual outbred compared to
      inbred mice. Importantly, while prior infection provided both inbred and outbred
      cohorts of mice with protection against re-infection that was dependent on the
      dose of primary infection, levels of memory CD8 T cells generated and degree of
      protection against re-infection did not correlate with primary infection dose in
      all outbred mice. While variation in CD8 T cell responses to infection is not
      entirely surprising due to the genetic diversity present, analysis of infection
      induced immunity in outbred hosts may reveal hidden complexity in CD8 T cell
      responses in genetically diverse populations and might help us further bridge the
      gap between mouse and human studies.

PMID- 29213268
TI  - Exploring Non-Metabolic Functions of Glycolytic Enzymes in Immunity.
AB  - At the beginning of the twentieth century, discoveries in cancer research began
      to elucidate the idiosyncratic metabolic proclivities of tumor cells (1).
      Investigators postulated that revealing the distinct nutritional requirements of
      cells with unchecked growth potential would reveal targetable metabolic
      vulnerabilities by which their survival could be selectively curtailed. Soon
      thereafter, researchers in the field of immunology began drawing parallels
      between the metabolic characteristics of highly proliferative cancer cells and
      those of immune cells that respond to perceived threats to host physiology by
      invading tissues, clonally expanding, and generating vast amounts of pro
      inflammatory effector molecules to provide the host with protection. Throughout
      the past decade, increasing effort has gone into elucidating the biosynthetic and
      bioenergetic requirements of immune cells during inflammatory responses. It is
      now well established that, like tumor cells, immune cells must undergo metabolic
      adaptations to fulfill their effector functions (2, 3). Unraveling the metabolic
      adaptations that license inflammatory immune responses may lead to the
      development of novel classes of therapeutics for pathologies with prominent
      inflammatory components (e.g., autoimmunity). However, the translational
      potential of discoveries made toward this end is currently limited by the
      ubiquitous nature of the "pathologic" process being targeted: metabolism. Recent
      works have started to unravel unexpected non-metabolic functions for metabolic
      enzymes in the context of inflammation, including signaling and gene regulation.
      One way information gained through the study of immunometabolism may be leveraged
      for therapeutic benefit is by exploiting these non-canonical features of
      metabolic machinery, modulating their contribution to the immune response without
      impacting their basal metabolic functions. The focus of this review is to discuss
      the metabolically independent functions of glycolytic enzymes and how these could
      impact T cells, agents of the immune system that are commonly considered as
      orchestrators of auto-inflammatory processes.

PMID- 29213269
TI  - Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine
      Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A
      Randomized Controlled Trial.
AB  - Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63
      (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope
      string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable
      safety and promising immunogenicity in African adult and pediatric populations.
      If licensed, this vaccine could be given to infants receiving routine childhood
      immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co
      administered with routine Expanded Program on Immunization (EPI) vaccines.
      Methods: We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at
      first vaccination and randomized them to receive either ME-TRAP and EPI vaccines
      or EPI vaccines only. Safety was assessed by the description of vaccine-related
      adverse events (AEs). Immunogenicity was evaluated using IFNgamma enzyme-linked
      immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was
      performed to confirm all infants achieved protective titers to EPI vaccines.
      Results: The vaccines were well tolerated in all age groups with no vaccine
      related serious AEs. High-level TRAP-specific IgG and T cell responses were
      generated after boosting with MVA. CD8+ T cell responses, previously found to
      correlate with protection, were induced in all groups. Antibody responses to EPI
      vaccines were not altered significantly. Conclusion: Malaria vectored prime-boost
      vaccines co-administered with routine childhood immunizations were well
      tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did
      not reduce the immunogenicity of co-administered EPI vaccines, supporting further
      evaluation of this regimen in infant populations. Clinical Trial Registration:
      The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and
      the Pan-African Clinical Trials Registry (PACTR201402000749217).

PMID- 29213270
TI  - Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor
      Therapeutics.
AB  - Monoclonal antibodies have revolutionized cancer therapy. However, delivery to
      tumor cells in vivo is hampered by the large size (150 kDa) of conventional
      antibodies. The minimal target recognition module of a conventional antibody is
      composed of two non-covalently associated variable domains (VH and VL). The
      proper orientation of these domains is mediated by their hydrophobic interface
      and is stabilized by their linkage to disulfide-linked constant domains (CH1 and
      CL). VH and VL domains can be fused via a genetic linker into a single-chain
      variable fragment (scFv). scFv modules in turn can be fused to one another, e.g.,
      to generate a bispecific T-cell engager, or they can be fused in various
      orientations to antibody hinge and Fc domains to generate bi- and multispecific
      antibodies. However, the inherent hydrophobic interaction of VH and VL domains
      limits the stability and solubility of engineered antibodies, often causing
      aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody
      based human heavy chain antibodies (75 kDa) can overcome these limitations.
      Camelids naturally produce antibodies composed only of heavy chains in which the
      target recognition module is composed of a single variable domain (VHH or Nb).
      Advantageous features of nanobodies include their small size, high solubility,
      high stability, and excellent tissue penetration in vivo. Nanobodies can readily
      be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins
      and can be conjugated chemically at a specific site to drugs, radionuclides,
      photosensitizers, and nanoparticles. These properties make them particularly
      suited for specific and efficient targeting of tumors in vivo. Chimeric nanobody
      heavy chain antibodies combine advantageous features of nanobodies and human Fc
      domains in about half the size of a conventional antibody. In this review, we
      discuss recent developments and perspectives for applications of nanobodies and
      nanobody-based human heavy chain antibodies as antitumor therapeutics.

PMID- 29213272
TI  - Host Responses to Malassezia spp. in the Mammalian Skin.
AB  - The skin of mammalian organisms is home for a myriad of microbes. Many of these
      commensals are thought to have beneficial effects on the host by critically
      contributing to immune homeostasis. Consequently, dysbiosis can have detrimental
      effects for the host that may manifest with inflammatory diseases at the barrier
      tissue. Besides bacteria, fungi make an important contribution to the microbiota
      and among these, the yeast Malassezia widely dominates in most areas of the skin
      in healthy individuals. There is accumulating evidence that Malassezia spp. are
      involved in a variety of skin disorders in humans ranging from non- or mildly
      inflammatory conditions such as dandruff and pityriasis versicolor to more severe
      inflammatory skin diseases like seborrheic eczema and atopic dermatitis. In
      addition, Malassezia is strongly linked to the development of dermatitis and
      otitis externa in dogs. However, the association of Malassezia spp. with such
      diseases remains poorly characterized. Until now, studies on the fungus-host
      interaction remain sparse and they are mostly limited to experiments with
      isolated host cells in vitro. They suggest a multifaceted crosstalk of Malassezia
      spp. with the skin by direct activation of the host via conserved pattern
      recognition receptors and indirectly via the release of fungus-derived
      metabolites that can modulate the function of hematopoietic and/or non
      hematopoietic cells in the barrier tissue. In this review, we discuss our current
      understanding of the host response to Malassezia spp. in the mammalian skin.

PMID- 29213273
TI  - Targeting TRIM5alpha in HIV Cure Strategies for the CRISPR-Cas9 Era.
AB  - In the past decade, studies of innate immune activity against HIV-1 and other
      retroviruses have revealed a powerful array of host factors that can attack the
      virus at various stages of its life cycle in human and primate cells, raising the
      prospect that these antiviral factors could be manipulated in immunotherapeutic
      strategies for HIV infection. This has not proved straightforward: while HIV
      accessory genes encode proteins that subvert or destroy many of these restriction
      factors, others, such as human TRIM5alpha show limited potency against HIV-1.
      However, HIV-1 is much more susceptible to simian versions of TRIM5alpha: could
      this information be translated into the development of an effective gene therapy
      for HIV infection? Reigniting research into the restriction factor TRIM5alpha in
      the era of superior gene editing technology such as CRISPR-Cas9 presents an
      exciting opportunity to revisit this prospect.

PMID- 29213271
TI  - Visceral Inflammation and Immune Activation Stress the Brain.
AB  - Stress refers to a dynamic process in which the homeostasis of an organism is
      challenged, the outcome depending on the type, severity, and duration of
      stressors involved, the stress responses triggered, and the stress resilience of
      the organism. Importantly, the relationship between stress and the immune system
      is bidirectional, as not only stressors have an impact on immune function, but
      alterations in immune function themselves can elicit stress responses. Such
      bidirectional interactions have been prominently identified to occur in the
      gastrointestinal tract in which there is a close cross-talk between the gut
      microbiota and the local immune system, governed by the permeability of the
      intestinal mucosa. External stressors disturb the homeostasis between microbiota
      and gut, these disturbances being signaled to the brain via multiple
      communication pathways constituting the gut-brain axis, ultimately eliciting
      stress responses and perturbations of brain function. In view of these
      relationships, the present article sets out to highlight some of the interactions
      between peripheral immune activation, especially in the visceral system, and
      brain function, behavior, and stress coping. These issues are exemplified by the
      way through which the intestinal microbiota as well as microbe-associated
      molecular patterns including lipopolysaccharide communicate with the immune
      system and brain, and the mechanisms whereby overt inflammation in the GI tract
      impacts on emotional-affective behavior, pain sensitivity, and stress coping. The
      interactions between the peripheral immune system and the brain take place along
      the gut-brain axis, the major communication pathways of which comprise microbial
      metabolites, gut hormones, immune mediators, and sensory neurons. Through these
      signaling systems, several transmitter and neuropeptide systems within the brain
      are altered under conditions of peripheral immune stress, enabling adaptive
      processes related to stress coping and resilience to take place. These aspects of
      the impact of immune stress on molecular and behavioral processes in the brain
      have a bearing on several disturbances of mental health and highlight novel
      opportunities of therapeutic intervention.

PMID- 29213274
TI  - Natural Killer Cells in Antifungal Immunity.
AB  - Invasive fungal infections are still an important cause of morbidity and
      mortality in immunocompromised patients such as patients suffering from
      hematological malignancies or patients undergoing hematopoietic stem cell
      transplantion. In addition, other populations such as human immunodeficiency
      virus-patients are at higher risk for invasive fungal infection. Despite the
      availability of new antifungal compounds and better supportive care measures, the
      fatality rate of invasive fungal infection remained unacceptably high. It is
      therefore of major interest to improve our understanding of the host-pathogen
      interaction to develop new therapeutic approaches such as adoptive immunotherapy.
      As experimental methodologies have improved and we now better understand the
      complex network of the immune system, the insight in the interaction of the host
      with the fungus has significantly increased. It has become clear that host
      resistance to fungal infections is not only associated with strong innate
      immunity but that adaptive immunity (e.g., T cells) also plays an important role.
      The antifungal activity of natural killer (NK) cells has been underestimated for
      a long time. In vitro studies demonstrated that NK cells from murine and human
      origin are able to attack fungi of different genera and species. NK cells exhibit
      not only a direct antifungal activity via cytotoxic molecules but also an
      indirect antifungal activity via cytokines. However, it has been show that fungi
      exert immunosuppressive effects on NK cells. Whereas clinical data are scarce,
      animal models have clearly demonstrated that NK cells play an important role in
      the host response against invasive fungal infections. In this review, we
      summarize clinical data as well as results from in vitro and animal studies on
      the impact of NK cells on fungal pathogens.

PMID- 29213275
TI  - Dynamic Changes in Host Gene Expression following In Vitro Viral Mimic
      Stimulation in Crocodile Cells.
AB  - The initial control of viral infection in a host is dominated by a very well
      orchestrated early innate immune system; however, very little is known about the
      ability of a host to control viral infection outside of mammals. The reptiles
      offer an evolutionary bridge between the fish and mammals, with the crocodile
      having evolved from the archosauria clade that included the dinosaurs, and being
      the largest living reptile species. Using an RNA-seq approach, we have defined
      the dynamic changes of a passaged primary crocodile cell line to stimulation with
      both RNA and DNA viral mimics. Cells displayed a marked upregulation of many
      genes known to be involved in the mammalian response to viral infection,
      including viperin, Mx1, IRF7, IRF1, and RIG-I with approximately 10% of the genes
      being uncharacterized transcripts. Both pathway and genome analysis suggested
      that the crocodile may utilize the main known mammalian TLR and cytosolic
      antiviral RNA signaling pathways, with the pathways being responsible for sensing
      DNA viruses less clear. Viral mimic stimulation upregulated the type I
      interferon, IFN-Omega, with many known antiviral interferon-stimulated genes also
      being upregulated. This work demonstrates for the first time that reptiles show
      functional regulation of many known and unknown antiviral pathways and effector
      genes. An enhanced knowledge of these ancient antiviral pathways will not only
      add to our understanding of the host antiviral innate response in non-mammalian
      species, but is critical to fully comprehend the complexity of the mammalian
      innate immune response to viral infection.

PMID- 29213276
TI  - An Integrated "Multi-Omics" Comparison of Embryo and Endosperm Tissue-Specific
      Features and Their Impact on Rice Seed Quality.
AB  - Although rice is a key crop species, few studies have addressed both rice seed
      physiological and nutritional quality, especially at the tissue level. In this
      study, an exhaustive "multi-omics" dataset on the mature rice seed was obtained
      by combining transcriptomics, label-free shotgun proteomics and metabolomics from
      embryo and endosperm, independently. These high-throughput analyses provide a new
      insight on the tissue-specificity related to rice seed quality. Foremost, we
      pinpointed that extensive post-transcriptional regulations occur at the end of
      rice seed development such that the embryo proteome becomes much more diversified
      than the endosperm proteome. Secondly, we observed that survival in the dry state
      in each seed compartment depends on contrasted metabolic and enzymatic apparatus
      in the embryo and the endosperm, respectively. Thirdly, it was remarkable to
      identify two different sets of starch biosynthesis enzymes as well as seed
      storage proteins (glutelins) in both embryo and endosperm consistently with the
      supernumerary embryo hypothesis origin of the endosperm. The presence of a
      putative new glutelin with a possible embryonic favored abundance is described
      here for the first time. Finally, we quantified the rate of mRNA translation into
      proteins. Consistently, the embryonic panel of protein translation initiation
      factors is much more diverse than that of the endosperm. This work emphasizes the
      value of tissue-specificity-centered "multi-omics" study in the seed to highlight
      new features even from well-characterized pathways. It paves the way for future
      studies of critical genetic determinants of rice seed physiological and
      nutritional quality.

PMID- 29213277
TI  - Functional and Structural Characterization of a Receptor-Like Kinase Involved in
      Germination and Cell Expansion in Arabidopsis.
AB  - Leucine-rich repeat receptor-like kinases (LRR-RLKs) are widespread in different
      plant species and play important roles in growth and development. Germination
      inhibition is vital for the completion of seed maturation and cell expansion is a
      fundamental cellular process driving plant growth. Here, we report genetic and
      structural characterizations of a functionally uncharacterized LRR-RLK, named
      GRACE (Germination Repression and Cell Expansion receptor-like kinase).
      Overexpression of GRACE in Arabidopsis exhibited delayed germination, enlarged
      cotyledons, rosette leaves and stubbier petioles. Conversely, these phenotypes
      were reversed in the T-DNA insertion knock-down mutant grace-1 plants. A crystal
      structure of the extracellular domain of GRACE (GRACE-LRR) determined at the
      resolution of 3.0 A revealed that GRACE-LRR assumed a right-handed super-helical
      structure with an island domain (ID). Structural comparison showed that structure
      of the ID in GRACE-LRR is strikingly different from those observed in other LRR
      RLKs. This structural observation implies that GRACE might perceive a new ligand
      for signaling. Collectively, our data support roles of GRACE in repressing seed
      germination and promoting cell expansion of Arabidopsis, presumably by perception
      of unknown ligand(s).

PMID- 29213279
TI  - Scheduling multi-task jobs with extra utility in data centers.
AB  - This paper investigates the problem of maximizing utility for job scheduling
      where each job consists of multiple tasks, each task has utility and each job
      also has extra utility if all tasks of that job are completed. We provide a 2
      approximation algorithm for the single-machine case and a 2-approximation
      algorithm for the multi-machine problem. Both algorithms include two steps. The
      first step employs the Earliest Deadline First method to compute utility with
      only extra job utility, and it is proved that it obtains the optimal result for
      this sub-problem. The second step employs a Dynamic Programming method to compute
      utility without extra job utility, and it also derives the optimal result. An
      approximation result can then be obtained by combining the results of the two
      steps.

PMID- 29213278
TI  - Translating Measures of Biological Aging to Test Effectiveness of Geroprotective
      Interventions: What Can We Learn from Research on Telomeres?
AB  - Intervention studies in animals suggest molecular changes underlying age-related
      disease and disability can be slowed or reversed. To speed translation of these
      so-called "geroprotective" therapies to prevent age-related disease and
      disability in humans, biomarkers are needed that can track changes in the rate of
      human aging over the course of intervention trials. Algorithm methods that
      measure biological processes of aging from combinations of DNA methylation marks
      or clinical biomarkers show promise. To identify next steps for establishing
      utility of these algorithm-based measures of biological aging for geroprotector
      trials, we considered the history a candidate biomarker of aging that has
      received substantial research attention, telomere length. Although telomere
      length possesses compelling biology to recommend it as a biomarker of aging,
      mixed research findings have impeded clinical and epidemiologic translation.
      Strengths of telomeres that should be established for algorithm biomarkers of
      aging are correlation with chronological age across the lifespan, prediction of
      disease, disability, and early death, and responsiveness to risk and protective
      exposures. Key challenges in telomere research that algorithm biomarkers of aging
      must address are measurement precision and reliability, establishing links
      between longitudinal rates of change across repeated measurements and aging
      outcomes, and clarity over whether the biomarker is a causal mechanism of aging.
      These strengths and challenges suggest a research agenda to advance translation
      of algorithm-based aging biomarkers: establish validity in young-adult and
      midlife individuals; test responsiveness to exposures that shorten or extend
      healthy lifespan; and conduct repeated-measures longitudinal studies to test
      differential rates of change.

PMID- 29213280
TI  - Subthreshold Psychiatric Psychopathology in Functional Gastrointestinal
      Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?
AB  - Background and Aims: Functional gastrointestinal disorders (FGDs) are
      multifactorial disorders of the gut-brain interaction. This study investigated
      the prevalence of Axis I and spectrum disorders in patients with FGD and
      established the link between FGDs and psychopathological dimensions. Methods: A
      total of 135 consecutive patients with FGD were enrolled. The symptoms' severity
      was evaluated using questionnaires, while the psychiatric evaluation by clinical
      interviews established the presence/absence of mental (Diagnostic and Statistical
      Manual-4th edition, Axis I Diagnosis) or spectrum disorders. Results: Of the 135
      patients, 42 (32.3%) had functional dyspepsia, 52 (40.0%) had irritable bowel
      syndrome, 21 (16.2%) had functional bloating, and 20 (15.4%) had functional
      constipation. At least one psychiatric disorder was present in 46.9% of the
      patients, while a suprathreshold panic spectrum was present in 26.2%. Functional
      constipation was associated with depressive disorders (p < 0.05), while
      functional dyspepsia was related to the current major depressive episode (p <
      0.05). Obsessive-compulsive spectrum was correlated with the presence of
      functional constipation and irritable bowel syndrome (p < 0.05). Conclusion: The
      high prevalence of subthreshold psychiatric symptomatology in patients with FGD,
      which is likely to influence the expression of gastrointestinal symptoms,
      suggested the usefulness of psychological evaluation in patients with FGDs.

PMID- 29213281
TI  - The NIMO Scandinavian Study: A Prospective Observational Study of Iron
      Isomaltoside Treatment in Patients with Iron Deficiency.
AB  - Background: Intravenous iron allows for efficient and well-tolerated treatment in
      iron deficiency and is routinely used in diseases of the gastrointestinal tract.
      Objective: The aims of this study were to determine the probability of relapse of
      iron deficiency over time and to investigate treatment routine, effectiveness,
      and safety of iron isomaltoside. Methods: A total of 282 patients treated with
      iron isomaltoside were observed for two treatments or a minimum of one year.
      Results: Out of 282 patients, 82 had Crohn's disease and 67 had ulcerative
      colitis. Another 133 patients had chronic blood loss, malabsorption, or
      malignancy. Patients who received an iron isomaltoside dose above 1000 mg had a
      65% lower probability of needing retreatment compared with those given 1000 mg. A
      clinically significant treatment response was shown, but in 71/191 (37%) of
      patients, anaemia was not corrected. The mean dose given was 1100 mg, lower than
      the calculated total iron need of 1481 mg. Adverse drug reactions were reported
      in 4% of patients. Conclusion: Iron isomaltoside is effective with a good safety
      profile, and high doses reduce the need for retreatment over time. Several
      patients were anaemic after treatment, indicating that doses were inadequate for
      full iron correction. This trial is registered with NCT01900197.

PMID- 29213282
TI  - Determination of Mammalian Target of Rapamycin Hyperactivation as Prognostic
      Factor in Well-Differentiated Neuroendocrine Tumors.
AB  - Purpose: To evaluate the role of the activation of mTOR (phosphorylated mTOR, p
      mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well
      differentiated neuroendocrine tumors. Methods: A retrospective study was
      conducted on data from patients with diagnosis of neuroendocrine tumor originated
      from pancreas (pNET) or gastrointestinal tract (stomach, appendix, and ileus; GI
      NET) made between January 2003 and December 2004 and followed up at our
      institution. Archival material should be available for revision according to WHO
      2010 neuroendocrine tumor classification and for p-mTOR, SSTR2A, and IGF-1R
      immunostaining, calculating a quantitative score (QS). We evaluated clinical,
      pathological, and immunohistochemistry features for association with the presence
      of advanced disease at diagnosis and disease relapse in patients who have
      undergone radical surgery. Results: Archival material from 64 patients was
      analyzed (37 pNETs and 27 GI-NETs). In these patients, G2 grading, low SSTR2A QS,
      and high p-mTOR QS were associated with advanced disease at diagnosis at
      multivariate analysis. Risk of recurrence in 49 patients with R0-resected tumors
      was higher for G2 grading, stage IIIB-IV, low IGF-1R QS, and high p-mTOR QS at
      univariate analysis. Conclusions: With the limits of retrospective data,
      activation of m-TOR is correlated with advanced disease at diagnosis and with
      shorter disease-free survival after R0 resection. Validation through prospective
      studies is needed.

PMID- 29213283
TI  - Lateral Supratrochanteric Approach to Sciatic and Femoral Nerve Blocks in
      Children: A Feasibility Study.
AB  - Background: Sciatic and femoral nerve blocks (SNB and FNB) result in effective
      lower limb analgesia. Classical SNB and FNB require patient repositioning which
      can cause pain and discomfort. Alternative approaches to sciatic and femoral
      nerve blocks in supine patients can be useful. Materials and Methods:
      Neurostimulator-guided SNB and FNB from the lateral supratrochanteric approach
      were performed. Local anesthetic spread in SNB and FNB after radiographic
      opacification was analyzed. Time and number of attempts to perform blocks, needle
      depth, and clinical efficacy were assessed. Results: Mean needle passes number
      and procedure time for SNB were 2.5 +/- 0.3 and 2.4 +/- 0.2 min, respectively.
      Mean needle passes number and procedure time for FNB were 2.7 +/- 0.27 and 2.59
      +/- 0.23 min, respectively. Mean skin to nerve distance was 9.1 +/- 0.45 cm for
      SNB and 8.8 +/- 0.5 cm for FNB. Radiographic opacification of SNB showed local
      anesthetic spread close to the sacrum and involvement of sacral plexus nerve
      roots. Spread of local anesthetic in FNB was typical. Intraoperative fentanyl
      administration was required in 2 patients (9.5%) with mean dose 1.8 +/- 0.2
      mcg/kg. Mean postoperative pain score was 0.34 +/- 0.08 of 10. Conclusion: The
      lateral supratrochanteric approach to SNB and FNB in children can be an effective
      lower limb analgesic technique in supine patients. The trial is registered with
      ISRCTN70969666.

PMID- 29213284
TI  - Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors
      to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface
      Markers.
AB  - Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a
      chronic inflammation involving immunity. GC are immune suppressors, and the
      adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act
      in atherothrombotic inflammation involving immune cells (IMNC). Aim. To
      investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC
      in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH.
      Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH
      ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes
      (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for
      atherosclerosis previously associated with CDs. Results. Leuc, N, and MN
      correlated with CS (p < 0.05), WC (p < 0.001), WHR (p = 0.003), BMI (p < 0.001),
      and hs-CRP (p < 0.001). CD14++CD16+ (p = 0.047); CD14+CD16++ (p = 0.053) MN;
      CD15+ (p = 0.027); CD15+CD16+ (p = 0.008) N; and NK-Lym (p = 0.019) were higher
      in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 +/- 3.5%) versus ACTH-D CS (4.2
      +/- 1.9%) versus C (4.9 +/- 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p =
      0.039) and CD15+ N with hs-CRP (r = 0.446, p = 0.037). In multivariate analysis,
      Leuc, N, and MN depended on BMI (p = 0.021), WC (p = 0.002), and WHR (p = 0.014),
      while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p = 0.035). Conclusion.
      In CS, IMNC present changes in activation and adhesion CDs implicated in
      atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype,
      possibly due to the absence of the immune modulator effect of ACTH.

PMID- 29213285
TI  - Low Levels of Sex Hormone-Binding Globulin Constitute an Independent Risk Factor
      for Arterial Stiffness in Korean Women.
AB  - The association between sex hormone-binding globulin (SHBG) and arterial
      stiffness in women is not conclusive. In addition, obesity might also be involved
      in the relationship between SHBG and atherosclerosis. The aim of this study was
      to determine the relationship between SHBG and arterial stiffness in association
      with central obesity in women. This cross-sectional study included 381 women who
      participated in the health checkup programs in one hospital. The brachial-ankle
      pulse wave velocity (baPWV) was measured as a marker for arterial stiffness. A
      negative correlation was observed between SHBG levels and baPWV (rho = -0.281).
      The relationship was significant even after adjusting for potential confounders
      (beta = -0.087 in fully adjusted model). After considering the interaction
      between central obesity and SHBG levels, the significant association was evident
      only in obese women (P for interaction = 0.025). Adjustment for a 10-year
      atherosclerotic cardiovascular disease (ASCVD) risk scores, instead of each
      cardiovascular risk factor individually, did not affect the significance of the
      relationship between SHBG levels and baPWV. Serum levels of SHBG were negatively
      associated with arterial stiffness independent of cardiovascular risk factors or
      10-year ASCVD risk scores in Korean women. The relationship may be potentiated by
      central obesity.

PMID- 29213286
TI  - Survival of Five Strains of Shiga Toxigenic Escherichia coli in a Sausage
      Fermentation Model and Subsequent Sensitivity to Stress from Gastric Acid and
      Intestinal Fluid.
AB  - The ability of foodborne pathogens to exhibit adaptive responses to stressful
      conditions in foods may enhance their survival when passing through the
      gastrointestinal system. We aimed to determine whether Escherichia coli surviving
      stresses encountered during a model dry-fermented sausage (DFS) production
      process exhibit enhanced tolerance and survival in an in vitro gastrointestinal
      model. Salami sausage batters spiked with five E. coli isolates, including
      enterohaemorrhagic E. coli strains isolated from different DFS outbreaks, were
      fermented in a model DFS process (20 degrees C, 21 days). Control batters spiked
      with the same strains were stored at 4 degrees C for the same period. Samples
      from matured model sausages and controls were thereafter exposed to an in vitro
      digestion challenge. Gastric exposure (pH 3) resulted in considerably reduced
      survival of the E. coli strains that had undergone the model DFS process. This
      reduction continued after entering intestinal challenge (pH 8), but growth
      resumed after 120 min. When subjected to gastric challenge for 120 min, E. coli
      that had undergone the DFS process showed about 2.3 log10? lower survival
      compared with those kept in sausage batter at 4 degrees C. Our results indicated
      that E. coli strains surviving a model DFS process exhibited reduced tolerance to
      subsequent gastric challenge at low pH.

PMID- 29213287
TI  - Gastrointestinal Symptoms and Elevated Levels of Anti-Saccharomyces cerevisiae
      Antibodies Are Associated with Higher Disease Activity in Colombian Patients with
      Spondyloarthritis.
AB  - Background: Spondyloarthritis (SpA) is a group of articular inflammatory
      rheumatic diseases that their gastrointestinal manifestations are around 10% of
      their extra-articular symptoms, supporting that the inflammatory response of the
      intestinal mucosa could be associated with the clinical status. Objectives: To
      investigate the association between gastrointestinal symptoms and autoantibodies
      and disease activity between SpA patients, healthy subjects (HS), and patients
      with inflammatory bowel disease (IBD). Methods: 102 SpA patients, 29 IBD
      patients, and 117 HS were included. Autoantibodies as ASCA, ANCA, anti-tTG, anti
      DGP, ANA, and IgA were measured. The patients were assessed to evaluate clinical
      and gastrointestinal symptoms. An association analysis was performed using Chi
      square test and a logistic regression. Results: Significant differences were
      found for ASCA levels in SpA (28.2%) compared to IBD (14.2%) and HS (6.0%) (p =
      0.029), as well as for ANAS in SpA (49.5%) and IBD (37.9%) (p < 0.001) and
      abdominal pain (p = 0.012) between SpA (54.3%) and IBD (27.5%). Significant
      associations were found between BASDAI > 4 and gastrointestinal symptoms (p <
      0.05) and IgA (p = 0.007). The association for abdominal bloating was maintained
      (OR: 3.93, CI-95%, 1.14-13.56; p = 0.030). Conclusions: Gastrointestinal
      symptoms, ASCA, ANAS, and IgA levels were associated with high disease activity
      in SpA compared with IBD and HS.

PMID- 29213288
TI  - MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament
      Stem Cells by Targeting ATF4.
AB  - Periodontitis is the main cause of adult tooth loss. Stem cell-based tissue
      engineering has become a promising therapy for periodontitis treatment. To date,
      human periodontal ligament stem cells (hPDLSCs) have been shown to be a favorable
      source for tissue engineering, but modulatory mechanisms of hPDLSCs remain
      unclear. Approximately 60% of mammalian genes are the targets of over 2000 miRNAs
      in multiple human cell types, and miRNAs are able to influence various biological
      processes in the human body, including bone formation. In this study, we found
      that after osteogenic induction, miR-214 was significantly decreased in hPDLSCs;
      therefore, we examined the effects of miR-214 on osteogenic differentiation.
      Computational miRNA target prediction analyses and luciferase reporter assays
      revealed that activating transcription factor 4 (ATF4) is a direct target of miR
      214. We prepared cells overexpressing miR-214 and found that miR-214 negatively
      regulates osteogenic differentiation of hPDLSCs. For the target of miR-214, ATF4
      protein expression level was decreased after induction. In conclusion, we found
      that miR-214-ATF4 axis is a novel pathway for regulating hPDLSC osteogenic
      differentiation.

PMID- 29213289
TI  - Endometritis and In Vitro PGE2 Challenge Modify Properties of Cattle Endometrial
      Mesenchymal Stem Cells and Their Transcriptomic Profile.
AB  - Mesenchymal stem cells (MSCs) were isolated and characterized from postpartum
      bovine endometrium of animals with subclinical (n = 5) and clinical endometritis
      (n = 3) and healthy puerperal females (n = 5). Cells isolated displayed mean
      morphological features of MSCs and underwent osteogenic, chondrogenic, and
      adipogenic differentiation after induction (healthy and subclinical). Cells from
      cows with clinical endometritis did not undergo adipogenic differentiation. All
      cells expressed mRNAs for selected MSC markers. Endometrial MSCs were challenged
      in vitro with PGE2 at concentrations of 0, 1, 3, and 10 MUM, and their global
      transcriptomic profile was studied. Overall, 1127 genes were differentially
      expressed between unchallenged cells and cells treated with PGE2 at all
      concentrations (763 up- and 364 downregulated, fold change > 2, and P < 0.05).
      The pathways affected the most by the PGE2 challenge were immune response,
      angiogenesis, and cell proliferation. In conclusion, we demonstrated that healthy
      puerperal bovine endometrium contains MSCs and that endometritis modifies and
      limits some functional characteristics of these cells, such as their ability to
      proceed to adipogenic differentiation. Also, PGE2, an inflammatory mediator of
      endometritis, modifies the transcriptomic profile of endometrial MSCs. A similar
      situation may occur during inflammation associated with endometritis, therefore
      affecting the main properties of endometrial MSCs.

PMID- 29213290
TI  - Effect of Isolation Technique and Location on the Phenotype of Human Corneal
      Stroma-Derived Cells.
AB  - Purpose: To determine the effect of the isolation technique and location upon the
      phenotype of human corneal stroma-derived cells (CSCs). Methods: CSCs were
      isolated from the corneal stroma center and periphery using the explant or
      enzymatic digestion technique. The native tissue was stained for functional
      markers, while cultured cells were analysed by FACS. PCR was used to determine
      gene expression in the cultured versus native cells. Results: The native stroma
      was positive for alpha-actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin.
      Cultured cells expressed CD73, CD90, CD105, CD51, Nestin, CD49a, CD49d, ABCG2,
      and CD47. PCR demonstrated a significant upregulation of ALDH1A1, AQP1, ITGB4,
      KLF4, CD31, CD34, and CXCR4 in the native tissue, while the expression of ABCG2,
      ITGAV, Nestin, CD73, CD90, CD105, and Vimentin were significantly higher in the
      cultured cells. GPC did not change. Conclusion: The study finds no significant
      difference between the phenotype of CSCs generated by the explant or enzymatic
      digestion technique from the center or periphery of the stroma. Isolation of the
      cells can be performed without regard to the location and isolation technique
      used for research. Cultivated CSCs undergo a complete surface marker and genotype
      profile change compared to the state in situ.

PMID- 29213291
TI  - Apolipoprotein E polymorphism and the risk of aneurysmal subarachnoid hemorrhage
      in a South Indian population.
AB  - Background: The rupture of a brain aneurysm causes bleeding in the subarachnoid
      space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated
      the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a
      South Indian population. Methods: The study was performed on 200 subjects with
      aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate
      DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic
      discrimination assay. Statistical software R.3.0.11 was used to statistically
      analyze the data and a p value < 0.05 was considered as statistically
      significant. Results: We found a significant association with the risk of aSAH in
      epsilon3/ epsilon4 genetic model (OR = 1.91, 95% CI = 1.16-3.14, p = 0.01).
      However, in the other genetic models and allele frequency, there was no
      significant association with the risk of aSAH. In subtyping, we found a
      significant association of epsilon2 allele frequency with posterior communicating
      artery (PCOM) aneurysm (OR = 3.59, 95% CI = 1.11-11.64, p = 0.03). Conclusion:
      Our results suggest that APOE polymorphism has an influence on the risk of aSAH
      in this South Indian population, specifically in the PCOM subtype.

PMID- 29213292
TI  - IFN-lambda1 in CHO cells: its expression and biological activity.
AB  - Background: Many studies have investigated the characteristics and biological
      activities of type III interferon (IFN), finding that it has similar features to
      type I IFN but also unique actions because it is recognized by a different
      receptor. Results: A full-length recombinant human IFN-lambda1 (rhIFN-lambda1)
      cDNA was cloned into the pDF expression vector and stably expressed in Flp-In-CHO
      cells. After four purification steps (ammonium sulfate precipitation, SP
      Sepharose chromatography, Blue Sepharose 6 fast flow affinity chromatography and
      molecular sieve chromatography), the rhIFN-lambda1 had a purity of about 90% and
      was found to have the predicted biological activities. The anti-viral activity of
      rhIFN-lambda1 was determined as 106 IU/mg using the vesicular stomatitis virus
      (WISH-VSV) assay system. The anti-proliferation activity of rhIFN-lambda1 was
      measured using the MTS method and the growth inhibition ratio was 57% higher than
      that for recombinant human IFN-alpha2b (rhIFN-alpha2b) when the rhIFN-lambda1
      concentration was 1000 IU/ml. rhIFN-lambda1 had lower natural killer cell
      cytotoxicity than rhIFN-alpha2b. Conclusion: The Flp-In-CHO system is suitable
      for stably expressing rhIFN-lambda1 that possesses the predicted anti-viral, anti
      proliferation and natural killer cell cytotoxicity-promoting activities.

PMID- 29213294
TI  - Conversational fluency and executive function in adolescents with conduct
      disorder.
AB  - Background: EF impairments are known to occur among adolescents with conduct
      disorder (CD) but their influence on communication ability is not well
      understood. The purpose of this study was to relate scores on a clinical EF
      questionnaire to performance on a communication task. Extemporaneous conversation
      was chosen as the target task, because it places a high demand on EFs and it is a
      critical medium for adolescent social development. Material and Methods: The
      participants were 18 incarcerated adolescents with conduct disorder (I-CD), 12
      incarcerated adolescents without CD (I-NCD), and 26 typically developing (TD) non
      incarcerated adolescents. Participants completed the Self-Report form of the
      Behavior Rating Inventory of Executive Function (BRIEF) and extemporaneous
      conversations. Results: The I-CD and I-NCD groups produced four times more
      dysfluencies in conversation than the TD group. There was also a significant
      group effect on BRIEF subscores for executive memory (TD vs. I-CD), but not for
      planning and organization. Fluency data correlated significantly with BRIEF
      scores for executive memory, and the combination of fluency and BRIEF data
      accounted for 65% of the variance in group membership between TD adolescents and
      their incarcerated peers, regardless of CD diagnosis. Conclusions: BRIEF scores
      seem to be related to performance on communication tasks relevant for adolescents
      in daily living. Our results also revealed very high dysfluency rates among
      incarcerated juveniles. The EF and conversation measures differentiated
      incarcerated vs. non-incarcerated juveniles, but were less sensitive to CD.

PMID- 29213293
TI  - Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic
      differentiation through Foxg1.
AB  - Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen
      derived dipeptides. We previously reported that Pro-Hyp promotes the
      differentiation of osteoblasts by increasing Runx2, osterix and Col1alpha1 mRNA
      expression levels. Here, to elucidate the mechanism of Pro-Hyp promotion of
      osteoblast differentiation, we focus on the involvement of Foxo1 in osteoblast
      differentiation via Runx2 regulation and the role of Foxg1 in Foxo1 regulation.
      The addition of Pro-Hyp had no effect on MC3T3-E1 cell proliferation in Foxo1- or
      Foxg1-knockdown cells. In Foxo1-knockdown cells, the addition of Pro-Hyp
      increased ALP activity, but in Foxg1-knockdown cells, it had no effect on ALP
      activity. An enhancing effect of Pro-Hyp on the Runx2 and osterix expression
      levels was observed in Foxo1-knockdown cells. However, no enhancing effect of Pro
      Hyp on osteoblastic gene expression was observed when Foxg1 was knocked down.
      These results demonstrate that Pro-Hyp promotes osteoblastic MC3T3-E1 cell
      differentiation and upregulation of osteogenic genes via Foxg1 expression.

PMID- 29213296
TI  - Comparison of the characteristics of suicide attempters with major depressive
      disorder and those with no psychiatric diagnosis in emergency departments of
      general hospitals in China.
AB  - Background: Major depressive disorder (MDD) is a known major risk factor for
      suicide due to the high suicide mortality. However, studies comparing the
      characteristics of suicide attempters with major depressive disorder and those
      with no psychiatric diagnosis in China are very limited. This study examined and
      compared the sociodemographic and psychological characteristics of suicide
      attempters with MDD and those with no psychiatric diagnosis in emergency
      departments of general hospitals to better understand the risk factors for
      suicide attempts in China. Methods: All subjects were enrolled in the study
      between June 2007 and January 2008. A total of 127 suicide attempters-54 with MDD
      and 73 with no psychiatric diagnosis-were enrolled. The sociodemographic and
      clinical characteristics were compared between two groups using the statistical
      analysis performed using frequency distribution, Student's t test, Chi-square
      test, and Fisher's exact test and a logistic regression model. Results: Suicide
      attempters with MDD were more likely to be more depressive, older, divorced or
      separated, unemployed, and living alone, and more likely to write a suicide note,
      have suicide ideation, and be motivated by reducing pain and burden. Suicide
      attempters with no psychiatric diagnosis were more likely to be younger and more
      impulsive, have self-rescue, and be motivated by threatening or taking revenge on
      others. Multivariate logistic regression analysis identified the following
      independent predictors of suicide attempts in individuals with MDD: a lower score
      on the quality of life scale, more years of education, and suicide ideation.
      Conclusions: The present study found both similarities and differences in the
      sociodemographic and clinical characteristics of suicide attempters with MDD and
      those with no psychiatric diagnosis in the emergency departments of general
      hospitals in China. These findings will help us to recognize the characteristics
      of suicide attempters in both groups and develop specific interventions for the
      two types of suicide attempters to prevent future suicide in China. For example,
      the suicide attempters with MDD in the emergency departments must be advised to
      the psychological clinic.

PMID- 29213295
TI  - Trabecular architecture in the forelimb epiphyses of extant xenarthrans
      (Mammalia).
AB  - Background: Bone structure has a crucial role in the functional adaptations that
      allow vertebrates to conduct their diverse lifestyles. Much has been documented
      regarding the diaphyseal structure of long bones of tetrapods. However, the
      architecture of trabecular bone, which is for instance found within the epiphyses
      of long bones, and which has been shown experimentally to be extremely plastic,
      has received little attention in the context of lifestyle adaptations (virtually
      only in primates). We therefore investigated the forelimb epiphyses of extant
      xenarthrans, the placental mammals including the sloths, anteaters, and
      armadillos. They are characterised by several lifestyles and degrees of
      fossoriality involving distinct uses of their forelimb. We used micro computed
      tomography data to acquire 3D trabecular parameters at regions of interest (ROIs)
      for all extant genera of xenarthrans (with replicates). Traditional, spherical,
      and phylogenetically informed statistics (including the consideration of size
      effects) were used to characterise the functional signal of these parameters.
      Results: Several trabecular parameters yielded functional distinctions. The main
      direction of the trabeculae distinguished lifestyle categories for one ROI (the
      radial trochlea). Among the other trabecular parameters, it is the degree of
      anisotropy (i.e., a preferential alignment of the trabeculae) that yielded the
      clearest functional signal. For all ROIs, the armadillos, which represent the
      fully terrestrial and fossorial category, were found as characterised by a
      greater degree of anisotropy (i.e., more aligned trabeculae). Furthermore, the
      trabeculae of the humeral head of the most fossorial armadillos were also found
      to be more anisotropic than in the less fossorial species. Conclusions: Most
      parameters were marked by an important intraspecific variability and by a size
      effect, which could, at least partly, be masking the functional signal. But for
      some parameters, the degree of anisotropy in particular, a clear functional
      distinction was recovered. Along with data on primates, our findings suggest that
      a trabecular architecture characterised by a greater degree of anisotropy is to
      be expected in species in which the relevant epiphyses withstand a restricted
      range of load directions. Trabecular architecture therefore is a promising
      research avenue for the reconstruction of lifestyles in extinct or cryptic
      species.

PMID- 29213297
TI  - Infant feeding pattern in the first six months of age in USA: a follow-up study.
AB  - Background: Infant feeding may consist of direct breastfeeding (DBF), pumping and
      bottle feeding (P&F), formula feeding (FF), solid food feeding (SFF), and any
      combination. An accurate evaluation of infant feeding requires descriptions of
      different patterns, consistency, and transition over time. Methods: In United
      States of America, the Infant Feeding Practice Study II collected information on
      the mode of feeding on nine occasions in 12 months. We focused on the first 6
      months with six feeding occasions. To determine the longitudinal patterns of
      feeding the latent class transition analyses was applied and assessed the
      transition probabilities between these classes over time. Results: Over 6 months,
      1899 mothers provided feeding information. In month 1 the largest latent class is
      FF (32.9%) followed by DBF (23.8%). In month 2, a substantial proportion of the
      FF class included SFF; which increases over time. A not allocated class, due to
      missing information was identified in months 1-3, transitions to SFF starting in
      month 4 (8.9%). In month 1, two mixed patterns exist: DBF and P&F combined with
      FF (13.9%) and DBF combined with P&F (18.7%). The triple combination of DBF, P&F,
      and FF (13.9%) became FF in month 2 (transition probability: 24.8%), and DBF in
      combination with P&F (transition probability: 49.1%). The pattern of DBF combined
      with P&F is relatively stable until month 4, when at least 50% of these infants
      receive solid food. Only 23-26% of the infants receive direct breastfeeding (DBF)
      in months 1-4, in month 5-6 SFF is added. Mothers who used FF were less educated
      and employed fulltime. Mothers who smoke and not residing in the west of the
      United States were also more likely to practice formula feeding. Conclusion:
      Infant feeding is complex. Breastfeeding is not predominant and we additionally
      considered the mixed patterns of feeding. To facilitate direct breastfeeding, a
      substantial increase in the duration of maternal leave is necessary in the United
      States.

PMID- 29213298
TI  - Reproducible genomic DNA preparation from diverse crop species for molecular
      genetic applications.
AB  - Background: Several high-throughput molecular genetic analyses rely on high
      quality genomic DNA. Copurification of other molecules can negatively impact the
      functionality of plant DNA preparations employed in these procedures. Isolating
      DNA from agronomically important crops, such as sugarcane, rice, citrus, potato
      and tomato is a challenge due to the presence of high fiber, polysaccharides, or
      secondary metabolites. We present a simplified, rapid and reproducible SDS-based
      method that provides high-quality and -quantity of DNA from small amounts of leaf
      tissue, as required by the emerging biotechnology and molecular genetic
      applications. Results: We developed the TENS-CO method as a simplified SDS-based
      isolation procedure with sequential steps of purification to remove
      polysaccharides and polyphenols using 2-mercaptoethanol and potassium acetate,
      chloroform partitioning, and sodium acetate/ethanol precipitation to yield high
      quantity and -quality DNA consistently from small amounts of tissue (0.15 g) for
      different plant species. The method is simplified and rapid in terms of requiring
      minimal manipulation, smaller extraction volume, reduced homogenization time (20
      s) and DNA precipitation (one precipitation for 1 h). The method has been
      demonstrated to accelerate screening of large amounts of plant tissues from
      species that are rich in polysaccharides and secondary metabolites for Southern
      blot analysis of reporter gene overexpressing lines, pathogen detection by
      quantitative PCR, and genotyping of disease-resistant plants using marker
      assisted selection. Conclusion: To facilitate molecular genetic studies in major
      agronomical crops, we have developed the TENS-CO method as a simple, rapid,
      reproducible and scalable protocol enabling efficient and robust isolation of
      high-quality and -quantity DNA from small amounts of tissue from sugarcane, rice,
      citrus, potato, and tomato, thereby reducing significantly the time and resources
      used for DNA isolation.

PMID- 29213299
TI  - Cervical cancer patients presentation and survival in the only oncology referral
      hospital, Ethiopia: a retrospective cohort study.
AB  - Background: Women infected with Human Immune Deficiency Virus (HIV) are assumed
      to be at higher risk of developing Cervical Cancer (CC). This is due to a rapid
      progression of pre-invasive to invasive lesions. However, evidences suggest, due
      to the availability of antiretroviral therapy (ART) and care services; an
      improved survival and treatment outcome of CC patients (CCPs) with HIV infection
      is expected. Objective: The aim of this study is to examine the clinical
      characteristics and survival of of CCPs registered at the radiotherapy center of
      Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University, Ethiopia.
      Methods: We conducted a retrospective cohort study. Data from 1655 CCPs diagnosed
      between September 2008 and September 2012 were included. The primary endpoint was
      death from any cause. Kaplan-Meier estimates were compared using the log-rank
      test. Cox proportional hazards regression model was used to identify predictors
      of death. Data were analyzed using STATA version IC/14. Results: The mean age of
      all patients was 49 years (SD = 11.6 years). Of all CCPs, 139 (8.4%) were HIV
      positive, 372 (22.5%) patients had a known negative HIV status and 1144 (69.1%)
      patients were asymptomatic with unknown HIV status. Due to late stage and waiting
      times, only 13.5% of the patients received curative radiotherapy doses. HIV
      positive CCPs presented more often with advanced disease compared to HIV negative
      CCPs ((44.6%) versus 39.7%, p = 0.007). There was no significant difference in
      survival between HIV-positive and HIV-negative CCPs. Older age (HR = 2.01; 95%
      CI, 1.01,-4.05), advanced disease (HR = 2.6; 95% CI, 1.67-4.04) and baseline
      anemia (HR = 1.65; 95% CI, 1.24, 2.20) were independent predictors for higher
      risk of death. Conclusion: Survival rates of CCPs did not differ according to HIV
      status. The risk of death was higher for patients with older age, advanced
      disease and anemia. HIV patients should be screened for CC according to
      guidelines to avoid late presentation.

PMID- 29213300
TI  - Measuring healthy behaviours using the stages of change model: an investigation
      into the physical activity and nutrition behaviours of Australian miners.
AB  - Background: Obesity is one of the fastest growing modern day epidemics affecting
      preventable disease and premature deaths. Healthy lifestyle behaviours, such as
      physical activity and nutritional consumption, have been shown to reduce the
      likelihood of obesity and obesity related health risks. Originally designed for
      measurement of unhealthy behaviours, the Stages of Change model, describes
      'precontemplators' as individuals who engage in the unhealthy behaviour, are
      unaware that their behaviour is problematic, and are resistant to change. The aim
      of this study was to refine and assess the measures of the Stages of Change model
      in order to achieve a concise and reliable classification of precontemplators, in
      the context of healthy behaviours. Methods: Eight hundred and ninety-seven
      employees participated in a health survey measuring current health behaviours and
      stage of change. This study compared a traditional precontemplation measure to a
      modified version in the assessment of two healthy behaviours: physical activity
      and fruit and vegetable consumption. Results: The modified measure was more
      accurate and captured fewer individuals currently meeting the guideline for both
      physical activity and nutrition, compared to the traditional measure of stages of
      change. However, across all stages of change, the measure incorrectly classified
      some employees with regards to meeting health guidelines. Conclusions: When
      applied to healthy behaviours, the stages of change measure for precontemplation
      should be further refined to reflect knowledge that the behaviour is unhealthy,
      and apathy to change. Additionally, measures should define health guidelines to
      increase reliable classification across all stages of change. The findings can be
      applied to inform the design and implementation of health promotion strategies
      targeting obesity related lifestyle behaviours in the general population.

PMID- 29213301
TI  - Including refugees in disease elimination: challenges observed from a sleeping
      sickness programme in Uganda.
AB  - Background: Ensuring equity between forcibly-displaced and host area populations
      is a key challenge for global elimination programmes. We studied Uganda's
      response to the recent refugee influx from South Sudan to identify key governance
      and operational lessons for national sleeping sickness programmes working with
      displaced populations today. A refugee policy which favours integration of
      primary healthcare services for refugee and host populations and the availability
      of rapid diagnostic tests (RDTs) to detect sleeping sickness at this health
      system level makes Uganda well-placed to include refugees in sleeping sickness
      surveillance. Methods: Using ethnographic observations of coordination meetings,
      review of programme data, interviews with sleeping sickness and refugee
      authorities and group discussions with health staff and refugees (2013-2016), we
      nevertheless identified some key challenges to equitably integrating refugees
      into government sleeping sickness surveillance. Results: Despite fears that
      refugees were at risk of disease and posed a threat to elimination, six months
      into the response, programme coordinators progressed to a sentinel surveillance
      strategy in districts hosting the highest concentrations of refugees. This meant
      that RDTs, the programme's primary surveillance tool, were removed from most
      refugee-serving facilities, exacerbating existing inequitable access to
      surveillance and leading refugees to claim that their access to sleeping sickness
      tests had been better in South Sudan. This was not intentionally done to exclude
      refugees from care, rather, four key governance challenges made it difficult for
      the programme to recognise and correct inequities affecting refugees: (a)
      perceived donor pressure to reduce the sleeping sickness programme's scope
      without clear international elimination guidance on surveillance quality; (b) a
      problematic history of programme relations with refugee-hosting districts which
      strained supervision of surveillance quality; (c) difficulties that government
      health workers faced to produce good quality surveillance in a crisis; and (d)
      reluctant engagement between the sleeping sickness programme and humanitarian
      structures. Conclusions: Despite progressive policy intentions, several
      entrenched governance norms and practices worked against integration of refugees
      into the national sleeping sickness surveillance system. Elimination programmes
      which marginalise forced migrants risk unwittingly contributing to disease spread
      and reinforce social inequities, so new norms urgently need to be established at
      local, national and international levels.

PMID- 29213302
TI  - A comprehensive review of HIV/STI prevention and sexual and reproductive health
      services among sex Workers in Conflict-Affected Settings: call for an evidence-
      and rights-based approach in the humanitarian response.
AB  - Background: While the conditions in emergency humanitarian and conflict-affected
      settings often result in significant sex work economies, there is limited
      information on the social and structural conditions of sex work in these
      settings, and the impacts on HIV/STI prevention and access to sexual and
      reproductive health (SRH) services for sex workers. Our objective was to
      comprehensively review existing evidence on HIV/STI prevention and access to SRH
      services for sex workers in conflict-affected settings globally. Methods: We
      conducted a comprehensive review of all peer review (both epidemiological and
      qualitative) and grey literature published in the last 15 years (2000-2015),
      focusing on 1) HIV/STI vulnerability or prevention, and/or 2) access to SRH
      services for sex workers in conflict-affected settings. Five databases were
      searched, using combinations of sex work, conflict/mobility, HIV/STI, and SRH
      service terms. Relevant peer-reviewed and grey literature were also hand
      searched, and key papers were cross-referenced for additional material. Results:
      Five hundred fifty one records were screened and 416 records reviewed. Of 33
      records describing HIV/STI prevention and/or access to SRH services among sex
      workers in conflict-affected settings, 24 were from sub-Saharan Africa; 18
      studies described the results of primary research (13 quantitative, 3
      qualitative, 2 mixed-methods) and 15 were non-primary research (e.g.,
      commentaries, policy reports, programmatic manuals). Available evidence indicated
      that within conflict-affected settings, SWs' capacity to engage in HIV/STI
      prevention and access SRH services is severely undermined by social and
      structural determinants including widespread violence and human rights
      violations, the collapse of livelihoods and traditional social structures, high
      levels of displacement, and difficulties accessing already scant health services
      due to stigma, discrimination and criminalization. Discussion/Conclusions: This
      review identified significant gaps in HIV/STI and SRH research, policy, and
      programming for conflict-affected sex workers, highlighting a critical gap in the
      humanitarian response. Sex worker-informed policies and interventions to promote
      HIV/STI prevention and access to HIV and SRH services using a rights-based
      approach are recommended, and further research on the degree to which conflict
      affected sex workers are accessing HIV/STI and SRH services is recommended.A
      paradigm shift from the behavioural and biomedical approach to a human rights
      based approach to HIV/STI prevention and SRH is strongly recommended.

PMID- 29213303
TI  - Climbing the mountain: experimental design for the efficient optimization of stem
      cell bioprocessing.
AB  - "To consult the statistician after an experiment is finished is often merely to
      ask him to conduct a post mortem examination. He can perhaps say what the
      experiment died of." - R.A. Fisher While this idea is relevant across research
      scales, its importance becomes critical when dealing with the inherently large,
      complex and expensive process of preparing material for cell-based therapies
      (CBTs). Effective and economically viable CBTs will depend on the establishment
      of optimized protocols for the production of the necessary cell types. Our
      ability to do this will depend in turn on the capacity to efficiently search
      through a multi-dimensional problem space of possible protocols in a timely and
      cost-effective manner. In this review we discuss approaches to, and illustrate
      examples of the application of statistical design of experiments to stem cell
      bioprocess optimization.

PMID- 29213305
TI  - A multiplexed magnetic tweezer with precision particle tracking and bi
      directional force control.
AB  - Background: In the past two decades, methods have been developed to measure the
      mechanical properties of single biomolecules. One of these methods, Magnetic
      tweezers, is amenable to aquisition of data on many single molecules
      simultaneously, but to take full advantage of this "multiplexing" ability, it is
      necessary to simultaneously incorprorate many capabilities that ahve been only
      demonstrated separately. Methods: Our custom built magnetic tweezer combines high
      multiplexing, precision bead tracking, and bi-directional force control into a
      flexible and stable platform for examining single molecule behavior. This was
      accomplished using electromagnets, which provide high temporal control of force
      while achieving force levels similar to permanent magnets via large paramagnetic
      beads. Results: Here we describe the instrument and its ability to apply 2-260 pN
      of force on up to 120 beads simultaneously, with a maximum spatial precision of
      12 nm using a variety of bead sizes and experimental techniques. We also
      demonstrate a novel method for increasing the precision of force estimations on
      heterogeneous paramagnetic beads using a combination of density separation and bi
      directional force correlation which reduces the coefficient of variation of force
      from 27% to 6%. We then use the instrument to examine the force dependence of
      uncoiling and recoiling velocity of type 1 fimbriae from Eschericia coli (E.
      coli) bacteria, and see similar results to previous studies. Conclusion: This
      platform provides a simple, effective, and flexible method for efficiently
      gathering single molecule force spectroscopy measurements.

PMID- 29213304
TI  - Engineering the human blood-brain barrier in vitro.
AB  - The blood-brain barrier (BBB) is the interface between the vasculature and the
      brain, regulating molecular and cellular transport into the brain. Endothelial
      cells (ECs) that form the capillary walls constitute the physical barrier but are
      dependent on interactions with other cell types. In vitro models are widely used
      in BBB research for mechanistic studies and drug screening. Current models have
      both biological and technical limitations. Here we review recent advances in stem
      cell engineering that have been utilized to create innovative platforms to
      replicate key features of the BBB. The development of human in vitro models is
      envisioned to enable new mechanistic investigations of BBB transport in central
      nervous system diseases.

PMID- 29213306
TI  - The TcEG1 beetle (Tribolium castaneum) cellulase produced in transgenic
      switchgrass is active at alkaline pH and auto-hydrolyzes biomass for increased
      cellobiose release.
AB  - Background: Genetically engineered biofuel crops, such as switchgrass (Panicum
      virgatum L.), that produce their own cell wall-digesting cellulase enzymes would
      reduce costs of cellulosic biofuel production. To date, non-bioenergy plant
      models have been used in nearly all studies assessing the synthesis and activity
      of plant-produced fungal and bacterial cellulases. One potential source for
      cellulolytic enzyme genes is herbivorous insects adapted to digest plant cell
      walls. Here we examine the potential of transgenic switchgrass-produced TcEG1
      cellulase from Tribolium castaneum (red flour beetle). This enzyme, when
      overproduced in Escherichia coli and Saccharomyces cerevisiae, efficiently
      digests cellulose at optima of 50  degrees C and pH 12.0. Results: TcEG1 that was
      produced in green transgenic switchgrass tissue had a range of endoglucanase
      activity of 0.16-0.05 units (uM glucose release/min/mg) at 50  degrees C and pH
      12.0. TcEG1 activity from air-dried leaves was unchanged from that from green
      tissue, but when tissue was dried in a desiccant oven (46  degrees C), specific
      enzyme activity decreased by 60%. When transgenic biomass was "dropped-in" into
      an alkaline buffer (pH 12.0) and allowed to incubate at 50  degrees C, cellobiose
      release was increased up to 77% over non-transgenic biomass. Saccharification was
      increased in one transgenic event by 28%, which had a concurrent decrease in
      lignin content of 9%. Histological analysis revealed an increase in cell wall
      thickness with no change to cell area or perimeter. Transgenic plants produced
      more, albeit narrower, tillers with equivalent dry biomass as the control.
      Conclusions: This work describes the first study in which an insect cellulase has
      been produced in transgenic plants; in this case, the dedicated bioenergy crop
      switchgrass. Switchgrass overexpressing the TcEG1 gene appeared to be
      morphologically similar to its non-transgenic control and produced equivalent dry
      biomass. Therefore, we propose TcEG1 transgenics could be bred with other
      transgenic germplasm (e.g., low-lignin lines) to yield new switchgrass with
      synergistically reduced recalcitrance to biofuel production. In addition,
      transgenes for other cell wall degrading enzymes may be stacked with TcEG1 in
      switchgrass to yield complementary cell wall digestion features and complete auto
      hydrolysis.

PMID- 29213307
TI  - The effect of switchgrass loadings on feedstock solubilization and biofuel
      production by Clostridium thermocellum.
AB  - Background: Efficient deconstruction and bioconversion of solids at high mass
      loadings is necessary to produce industrially relevant titers of biofuels from
      lignocellulosic biomass. To date, only a few studies have investigated the effect
      of solids loadings on microorganisms of interest for consolidated bioprocessing.
      Here, the effects that various switchgrass loadings have on Clostridium
      thermocellum solubilization and bioconversion are investigated. Results:
      Clostridium thermocellum was grown for 10 days on 10, 25, or 50 g/L switchgrass
      or Avicel at equivalent glucan loadings. Avicel was completely consumed at all
      loadings, but total cellulose solubilization decreased from 63 to 37% as
      switchgrass loadings increased from 10 to 50 g/L. Washed, spent switchgrass could
      be additionally hydrolyzed and fermented in second-round fermentations suggesting
      that access to fermentable substrates was not the limiting factor at higher
      feedstock loadings. Results from fermentations on Avicel or cellobiose using
      culture medium supplemented with 50% spent fermentation broth demonstrated that
      compounds present in the supernatants from the 25 or 50 g/L switchgrass loadings
      were the most inhibitory to continued fermentation. Conclusions: Recalcitrance
      alone cannot fully account for differences in solubilization and end-product
      formation between switchgrass and Avicel at increased substrate loadings.
      Experiments aimed at separating metabolic inhibition from inhibition of
      hydrolysis suggest that C. thermocellum's hydrolytic machinery is more vulnerable
      to inhibition from switchgrass-derived compounds than its fermentative
      metabolism.

PMID- 29213308
TI  - The effect of liquid hot water pretreatment on the chemical-structural alteration
      and the reduced recalcitrance in poplar.
AB  - Background: Hydrothermal pretreatment using liquid hot water (LHW) is capable of
      substantially reducing the cell wall recalcitrance of lignocellulosic biomass. It
      enhances the saccharification of polysaccharides, particularly cellulose, into
      glucose with relatively low capital required. Due to the close association with
      biomass recalcitrance, the structural change of the components of lignocellulosic
      materials during the pretreatment is crucial to understand pretreatment chemistry
      and advance the bio-economy. Although the LHW pretreatment has been extensively
      applied and studied, the molecular structural alteration during pretreatment and
      its significance to reduced recalcitrance have not been well understood. Results:
      We investigated the effects of LHW pretreatment with different severity factors
      (log R0) on the structural changes of fast-grown poplar (Populus trichocarpa).
      With the severity factor ranging from 3.6 to 4.2, LHW pretreatment resulted in a
      substantial xylan solubilization by 50-77% (w/w, dry matter). The molecular
      weights of the remained hemicellulose in pretreated solids also have been
      significantly reduced by 63-75% corresponding to LHW severity factor from 3.6 to
      4.2. In addition, LHW had a considerable impact on the cellulose structure. The
      cellulose crystallinity increased 6-9%, whereas its degree of polymerization
      decreased 35-65% after pretreatment. We found that the pretreatment severity had
      an empirical linear correlation with the xylan solubilization (R2 = 0.98, r = +
      0.99), hemicellulose molecular weight reduction (R2 = 0.97, r = - 0.96 and R2 =
      0.93, r = - 0.98 for number-average and weight-average degree of polymerization,
      respectively), and cellulose crystallinity index increase (R2 = 0.98, r = +
      0.99). The LHW pretreatment also resulted in small changes in lignin structure
      such as decrease of beta-O-4' ether linkages and removal of cinnamyl alcohol end
      group and acetyl group, while the S/G ratio of lignin in LHW pretreated poplar
      residue remained no significant change compared with the untreated poplar.
      Conclusions: This study revealed that the solubilization of xylan, the reduction
      of hemicellulose molecular weights and cellulose degree of polymerization, and
      the cleavage of alkyl-aryl ether bonds in lignin resulted from LHW pretreatment
      are critical factors associated with reduced cell wall recalcitrance. The
      chemical-structural changes of the three major components, cellulose, lignin, and
      hemicellulose, during LHW pretreatment provide useful and fundamental information
      of factors governing feedstock recalcitrance during hydrothermal pretreatment.

PMID- 29213309
TI  - Structure of a Thermobifida fusca lytic polysaccharide monooxygenase and
      mutagenesis of key residues.
AB  - Background: Auxiliary activity (AA) enzymes are produced by numerous bacterial
      and fungal species to assist in the degradation of biomass. These enzymes are
      abundant but have yet to be fully characterized. Here, we report the X-ray
      structure of Thermobifida fusca AA10A (TfAA10A), investigate mutational
      characterization of key surface residues near its active site, and explore the
      importance of the various domains of Thermobifida fusca AA10B (TfAA10B). The
      structure of TfAA10A is similar to other bacterial LPMOs (lytic polysaccharide
      monooxygenases), including signs of photo-reduction and a distorted active site,
      with mixed features showing both type I and II copper coordination. The point
      mutation experiments of TfAA10A show that Trp82 and Asn83 are needed for binding,
      but only Trp82 affects activity. The TfAA10B domain truncation mutants reveal
      that CBM2 is crucial for the binding of substrate, but that the X1 module does
      not affect binding or activity. Results: In TfAA10A, Trp82 and Asn83 are needed
      for binding, but only Trp82 affects activity. The TfAA10B domain truncation
      mutants reveal that CBM2 is crucial for substrate binding, but that the X1 module
      does not affect binding or activity. The structure of TfAA10A is similar to other
      bacterial lytic polysaccharide monooxygenases with mixed features showing both
      type I and II copper coordination. Conclusions: The role of LPMOs and the
      variability of abundance in genomes are not fully explored. LPMOs likely perform
      initial attacks into crystalline cellulose to allow larger processive cellulases
      to bind and attack, but the precise nature of their synergistic behavior remains
      to be definitively characterized.

PMID- 29213310
TI  - Xylan epitope profiling: an enhanced approach to study organ development
      dependent changes in xylan structure, biosynthesis, and deposition in plant cell
      walls.
AB  - Background: Xylan is a major hemicellulosic component in the cell walls of higher
      plants especially in the secondary walls of vascular cells which are playing
      important roles in physiological processes and overall mechanical strength. Being
      the second most abundant cell wall polymer after cellulose, xylan is an abundant
      non-cellulosic carbohydrate constituent of plant biomass. Xylan structures have
      been demonstrated to contribute to plant biomass recalcitrance during bioenergy
      applications. A critical understanding of xylan composition, structure, and
      biosynthesis in developing plant stems will allow an increased understanding of
      how cell walls are put together in this organ in a basic research, and, in
      applied research, will improve strategies in xylan engineering to reduce biomass
      recalcitrance for economically feasible biofuel production. Methods: We describe
      an approach to enable the monitoring of xylan epitope structures in cell walls
      during the stem maturation process in Arabidopsis. The technique integrates
      glycome profiling, an in vitro immunoanalytical platform, and in situ
      immunolocalisation to provide comprehensive details on the presence, relative
      abundances, and dynamics with which diverse xylan epitope structures are
      integrated to the cell walls throughout the stem maturation process. Results: Our
      experimental results and the supporting in silico analysis demonstrated that
      xylan deposition in stems occurs early on in stem development; however, xylan
      epitope types (representing substituted and unsubstituted regions on xylan
      backbone made of beta-(1,4)-linked xylose residues) and the strength of their
      integration into the final wall structure vary during stem maturation.
      Conclusions: Our novel approach thus provides a method to comprehensively survey
      the differences in xylan epitope patterning and deposition occurring in stem
      development and thereby providing a robust tool for characterising altered xylan
      integration patterns in cell walls during the stem maturation process in diverse
      plant cell wall biosynthetic mutants. Our findings also suggest that this
      approach could rapidly and reliably delineate xylan deposition patterns in the
      cell walls of plants belonging to diverse phylogenetic classes providing novel
      insights into the functional roles of xylans in overall growth and development.

PMID- 29213311
TI  - Expression of adhA from different organisms in Clostridium thermocellum.
AB  - Background: Clostridium thermocellum is a cellulolytic anaerobic thermophile that
      is a promising candidate for consolidated bioprocessing of lignocellulosic
      biomass into biofuels such as ethanol. It was previously shown that expressing
      Thermoanaerobacterium saccharolyticum adhA in C. thermocellum increases ethanol
      yield.In this study, we investigated expression of adhA genes from different
      organisms in Clostridium thermocellum. Methods: Based on sequence identity to T.
      saccharolyticum adhA, we chose adhA genes from 10 other organisms: Clostridium
      botulinum, Methanocaldococcus bathoardescens, Thermoanaerobacterium ethanolicus,
      Thermoanaerobacter mathranii, Thermococcus strain AN1, Thermoanaerobacterium
      thermosaccharolyticum, Caldicellulosiruptor saccharolyticus, Fervidobacterium
      nodosum, Marinitoga piezophila, and Thermotoga petrophila. All 11 adhA genes
      (including T. saccharolyticum adhA) were expressed in C. thermocellum and
      fermentation end products were analyzed. Results: All 11 adhA genes increased C.
      thermocellum ethanol yield compared to the empty-vector control. C. botulinum and
      T. ethanolicus adhA genes generated significantly higher ethanol yield than T.
      saccharolyticum adhA. Conclusion: Our results indicated that expressing adhA is
      an effective method of increasing ethanol yield in wild-type C. thermocellum, and
      that this appears to be a general property of adhA genes.

PMID- 29213312
TI  - Adding tetrahydrofuran to dilute acid pretreatment provides new insights into
      substrate changes that greatly enhance biomass deconstruction by Clostridium
      thermocellum and fungal enzymes.
AB  - Background: Consolidated bioprocessing (CBP) by anaerobes, such as Clostridium
      thermocellum, which combine enzyme production, hydrolysis, and fermentation are
      promising alternatives to historical economic challenges of using fungal enzymes
      for biological conversion of lignocellulosic biomass. However, limited research
      has integrated CBP with real pretreated biomass, and understanding how
      pretreatment impacts subsequent deconstruction by CBP vs. fungal enzymes can
      provide valuable insights into CBP and suggest other novel biomass deconstruction
      strategies. This study focused on determining the effect of pretreatment by
      dilute sulfuric acid alone (DA) and with tetrahydrofuran (THF) addition via co
      solvent-enhanced lignocellulosic fractionation (CELF) on deconstruction of corn
      stover and Populus with much different recalcitrance by C. thermocellum vs.
      fungal enzymes and changes in pretreated biomass related to these differences.
      Results: Coupling CELF fractionation of corn stover and Populus with subsequent
      CBP by the anaerobe C. thermocellum completely solubilized polysaccharides left
      in the pretreated solids within only 48 h without adding enzymes. These results
      were better than those from the conventional DA followed by either CBP or fungal
      enzymes or CELF followed by fungal enzyme hydrolysis, especially at viable enzyme
      loadings. Enzyme adsorption on CELF-pretreated corn stover and CELF-pretreated
      Populus solids were virtually equal, while DA improved the enzyme accessibility
      for corn stover more than Populus. Confocal scanning light microscopy (CSLM),
      transmission electron microscopy (TEM), and NMR characterization of solids from
      both pretreatments revealed differences in cell wall structure and lignin
      composition, location, coalescence, and migration-enhanced digestibility of CELF
      pretreated solids. Conclusions: Adding THF to DA pretreatment (CELF) greatly
      enhanced deconstruction of corn stover and Populus by fungal enzymes and C.
      thermocellum CBP, and the CELF-CBP tandem was agnostic to feedstock
      recalcitrance. Composition measurements, material balances, cellulase adsorption,
      and CSLM and TEM imaging revealed adding THF enhanced the enzyme accessibility,
      cell wall fractures, and cellular dislocation and cell wall delamination.
      Overall, enhanced deconstruction of CELF solids by enzymes and particularly by C.
      thermocellum could be related to lignin removal and alteration, thereby pointing
      to these factors being key contributors to biomass recalcitrance as a barrier to
      low-cost biological conversion to sustainable fuels.

PMID- 29213313
TI  - Agronomic performance of Populus deltoides trees engineered for biofuel
      production.
AB  - Background: One of the major barriers to the development of lignocellulosic
      feedstocks is the recalcitrance of plant cell walls to deconstruction and
      saccharification. Recalcitrance can be reduced by targeting genes involved in
      cell wall biosynthesis, but this can have unintended consequences that compromise
      the agronomic performance of the trees under field conditions. Here we report the
      results of a field trial of fourteen distinct transgenic Populus deltoides lines
      that had previously demonstrated reduced recalcitrance without yield penalties
      under greenhouse conditions. Results: Survival and productivity of the trial were
      excellent in the first year, and there was little evidence for reduced
      performance of the transgenic lines with modified target gene expression.
      Surprisingly, the most striking phenotypic effects in this trial were for two
      empty-vector control lines that had modified bud set and bud flush. This is most
      likely due to somaclonal variation or insertional mutagenesis. Traits related to
      yield, crown architecture, herbivory, pathogen response, and frost damage showed
      few significant differences between target gene transgenics and empty vector
      controls. However, there were a few interesting exceptions. Lines overexpressing
      the DUF231 gene, a putative O-acetyltransferase, showed early bud flush and
      marginally increased height growth. Lines overexpressing the DUF266 gene, a
      putative glycosyltransferase, had significantly decreased stem internode length
      and slightly higher volume index. Finally, lines overexpressing the PFD2 gene, a
      putative member of the prefoldin complex, had a slightly reduced volume index.
      Conclusions: This field trial demonstrates that these cell wall modifications,
      which decreased cell wall recalcitrance under laboratory conditions, did not
      seriously compromise first-year performance in the field, despite substantial
      challenges, including an outbreak of a stem boring insect (Gypsonoma
      haimbachiana), attack by a leaf rust pathogen (Melampsora spp.), and a late frost
      event. This bodes well for the potential utility of these lines as advanced
      biofuels feedstocks.

PMID- 29213314
TI  - Field-grown miR156 transgenic switchgrass reproduction, yield, global gene
      expression analysis, and bioconfinement.
AB  - Background: Genetic engineering has been effective in altering cell walls for
      biofuel production in the bioenergy crop, switchgrass (Panicum virgatum).
      However, regulatory issues arising from gene flow may prevent commercialization
      of engineered switchgrass in the eastern United States where the species is
      native. Depending on its expression level, microRNA156 (miR156) can reduce,
      delay, or eliminate flowering, which may serve to decrease transgene flow. In
      this unique field study of transgenic switchgrass that was permitted to flower,
      two low (T14 and T35) and two medium (T27 and T37) miR156-overexpressing 'Alamo'
      lines with the transgene under the control of the constitutive maize (Zea mays)
      ubiquitin 1 promoter, along with nontransgenic control plants, were grown in
      eastern Tennessee over two seasons. Results: miR156 expression was positively
      associated with decreased and delayed flowering in switchgrass. Line T27 did not
      flower during the 2-year study. Line T37 did flower, but not all plants produced
      panicles. Flowering was delayed in T37, resulting in 70.6% fewer flowers than
      controls during the second field year with commensurate decreased seed yield:
      1205 seeds per plant vs. 18,539 produced by each control. These results are
      notable given that line T37 produced equivalent vegetative aboveground biomass to
      the controls. miR156 transcript abundance of field-grown plants was congruent
      with greenhouse results. The five miR156 SQUAMOSA PROMOTER BINDING PROTEIN-LIKE
      (SPL) target genes had suppressed expression in one or more of the transgenic
      lines. Line T27, which had the highest miR156 overexpression, showed significant
      downregulation for all five SPL genes. On the contrary, line T35 had the lowest
      miR156 overexpression and had no significant change in any of the five SPL genes.
      Conclusions: Because of the research field's geographical features, this study
      was the first instance of any genetically engineered trait in switchgrass, in
      which experimental plants were allowed to flower in the field in the eastern
      U.S.; USDA-APHIS-BRS regulators allowed open flowering. We found that medium
      overexpression of miR156, e.g., line T37, resulted in delayed and reduced
      flowering accompanied by high biomass production. We propose that induced miR156
      expression could be further developed as a transgenic switchgrass bioconfinement
      tool to enable eventual commercialization.

PMID- 29213315
TI  - Comprehensive characterization of toxicity of fermentative metabolites on
      microbial growth.
AB  - Background: Volatile carboxylic acids, alcohols, and esters are natural
      fermentative products, typically derived from anaerobic digestion. These
      metabolites have important functional roles to regulate cellular metabolisms and
      broad use as food supplements, flavors and fragrances, solvents, and fuels.
      Comprehensive characterization of toxic effects of these metabolites on microbial
      growth under similar conditions is very limited. Results: We characterized a
      comprehensive list of thirty-two short-chain carboxylic acids, alcohols, and
      esters on microbial growth of Escherichia coli MG1655 under anaerobic conditions.
      We analyzed toxic effects of these metabolites on E. coli health, quantified by
      growth rate and cell mass, as a function of metabolite types, concentrations, and
      physiochemical properties including carbon number, chemical functional group,
      chain branching feature, energy density, total surface area, and hydrophobicity.
      Strain characterization revealed that these metabolites exert distinct toxic
      effects on E. coli health. We found that higher concentrations and/or carbon
      numbers of metabolites cause more severe growth inhibition. For the same carbon
      numbers and metabolite concentrations, we discovered that branched chain
      metabolites are less toxic than the linear chain ones. Remarkably, shorter alkyl
      esters (e.g., ethyl butyrate) appear less toxic than longer alkyl esters (e.g.,
      butyl acetate). Regardless of metabolites, hydrophobicity of a metabolite,
      governed by its physiochemical properties, strongly correlates with the
      metabolite's toxic effect on E. coli health. Conclusions: Short-chain alcohols,
      acids, and esters exhibit distinctive toxic effects on E. coli health.
      Hydrophobicity is a quantitative predictor to evaluate the toxic effect of a
      metabolite. This study sheds light on degrees of toxicity of fermentative
      metabolites on microbial health and further helps in the selection of desirable
      metabolites and hosts for industrial fermentation to overproduce them.

PMID- 29213316
TI  - Visualizing chemical functionality in plant cell walls.
AB  - Understanding plant cell wall cross-linking chemistry and polymeric architecture
      is key to the efficient utilization of biomass in all prospects from rational
      genetic modification to downstream chemical and biological conversion to produce
      fuels and value chemicals. In fact, the bulk properties of cell wall
      recalcitrance are collectively determined by its chemical features over a wide
      range of length scales from tissue, cellular to polymeric architectures.
      Microscopic visualization of cell walls from the nanometer to the micrometer
      scale offers an in situ approach to study their chemical functionality
      considering its spatial and chemical complexity, particularly the capabilities of
      characterizing biomass non-destructively and in real-time during conversion
      processes. Microscopic characterization has revealed heterogeneity in the
      distribution of chemical features, which would otherwise be hidden in bulk
      analysis. Key microscopic features include cell wall type, wall layering, and
      wall composition-especially cellulose and lignin distributions. Microscopic
      tools, such as atomic force microscopy, stimulated Raman scattering microscopy,
      and fluorescence microscopy, have been applied to investigations of cell wall
      structure and chemistry from the native wall to wall treated by thermal chemical
      pretreatment and enzymatic hydrolysis. While advancing our current understanding
      of plant cell wall recalcitrance and deconstruction, microscopic tools with
      improved spatial resolution will steadily enhance our fundamental understanding
      of cell wall function.

PMID- 29213317
TI  - Dynamic changes in transcriptome and cell wall composition underlying
      brassinosteroid-mediated lignification of switchgrass suspension cells.
AB  - Background: Plant cell walls contribute the majority of plant biomass that can be
      used to produce transportation fuels. However, the complexity and variability in
      composition and structure of cell walls, particularly the presence of lignin,
      negatively impacts their deconstruction for bioenergy. Metabolic and genetic
      changes associated with secondary wall development in the biofuel crop
      switchgrass (Panicum virgatum) have yet to be reported. Results: Our previous
      studies have established a cell suspension system for switchgrass, in which cell
      wall lignification can be induced by application of brassinolide (BL). We have
      now collected cell wall composition and microarray-based transcriptome profiles
      for BL-induced and non-induced suspension cultures to provide an overview of the
      dynamic changes in transcriptional reprogramming during BL-induced cell wall
      modification. From this analysis, we have identified changes in candidate genes
      involved in cell wall precursor synthesis, cellulose, hemicellulose, and pectin
      formation and ester-linkage generation. We have also identified a large number of
      transcription factors with expression correlated with lignin biosynthesis genes,
      among which are candidates for control of syringyl (S) lignin accumulation.
      Conclusion: Together, this work provides an overview of the dynamic compositional
      changes during brassinosteroid-induced cell wall remodeling, and identifies
      candidate genes for future plant genetic engineering to overcome cell wall
      recalcitrance.

PMID- 29213318
TI  - Targeted redox and energy cofactor metabolomics in Clostridium thermocellum and
      Thermoanaerobacterium saccharolyticum.
AB  - Background: Clostridium thermocellum and Thermoanaerobacterium saccharolyticum
      are prominent candidate biocatalysts that, together, can enable the direct biotic
      conversion of lignocellulosic biomass to ethanol. The imbalance and suboptimal
      turnover rates of redox cofactors are currently hindering engineering efforts to
      achieve higher bioproductivity in both organisms. Measuring relevant
      intracellular cofactor concentrations will help understand redox state of these
      cofactors and help identify a strategy to overcome these limitations; however,
      metabolomic determinations of these labile metabolites have historically proved
      challenging. Results: Through our validations, we verified the handling and
      storage stability of these metabolites, and verified extraction matrices and
      extraction solvent were not suppressing mass spectrometry signals. We recovered
      adenylate energy charge ratios (a main quality indicator) above 0.82 for all
      extractions. NADH/NAD+ values of 0.26 and 0.04 for an adhE-deficient strain of C.
      thermocellum and its parent, respectively, reflect the expected shift to a more
      reduced redox potential when a species lacks the ability to re-oxidize NADH by
      synthesizing ethanol. This method failed to yield reliable results with C. bescii
      and poor-growing strains of T. saccharolyticum. Conclusions: Our validated
      protocols demonstrate and validate the extraction and analysis of selected redox
      and energy-related metabolites from two candidate consolidated bioprocessing
      biocatalysts, C. thermocellum and T. saccharolyticum. This development and
      validation highlights the important, but often neglected, need to optimize and
      validate metabolomic protocols when adapting them to new cell or tissue types.

PMID- 29213319
TI  - Natural diversity of glycoside hydrolase family 48 exoglucanases: insights from
      structure.
AB  - Glycoside hydrolase (GH) family 48 is an understudied and increasingly important
      exoglucanase family found in the majority of bacterial cellulase systems.
      Moreover, many thermophilic enzyme systems contain GH48 enzymes. Deletion of GH48
      enzymes in these microorganisms results in drastic reduction in biomass
      deconstruction. Surprisingly, given their importance for these microorganisms,
      GH48s have intrinsically low cellulolytic activity but even in low ratios
      synergize greatly with GH9 endoglucanases. In this study, we explore the
      structural and enzymatic diversity of these enzymes across a wide range of
      temperature optima. We have crystallized one new GH48 module from Bacillus
      pumilus in a complex with cellobiose and cellohexaose (BpumGH48). We compare this
      structure to other known GH48 enzymes in an attempt to understand GH48
      structure/function relationships and draw general rules correlating amino acid
      sequences and secondary structures to thermostability in this GH family.

PMID- 29213320
TI  - Metabolome analysis reveals a role for glyceraldehyde 3-phosphate dehydrogenase
      in the inhibition of C. thermocellum by ethanol.
AB  - Background: Clostridium thermocellum is a promising microorganism for conversion
      of cellulosic biomass to biofuel, without added enzymes; however, the low ethanol
      titer produced by strains developed thus far is an obstacle to industrial
      application. Results: Here, we analyzed changes in the relative concentration of
      intracellular metabolites in response to gradual addition of ethanol to growing
      cultures. For C. thermocellum, we observed that ethanol tolerance, in experiments
      with gradual ethanol addition, was twofold higher than previously observed in
      response to a stepwise increase in the ethanol concentration, and appears to be
      due to a mechanism other than mutation. As ethanol concentrations increased, we
      found accumulation of metabolites upstream of the glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) reaction and depletion of metabolites downstream of that
      reaction. This pattern was not observed in the more ethanol-tolerant organism
      Thermoanaerobacterium saccharolyticum. We hypothesize that the Gapdh enzyme may
      have different properties in the two organisms. Our hypothesis is supported by
      enzyme assays showing greater sensitivity of the C. thermocellum enzyme to high
      levels of NADH, and by the increase in ethanol tolerance and production when the
      T. saccharolyticum gapdh was expressed in C. thermocellum. Conclusions: We have
      demonstrated that a metabolic bottleneck occurs at the GAPDH reaction when the
      growth of C. thermocellum is inhibited by high levels of ethanol. We then showed
      that this bottleneck could be relieved by expression of the gapdh gene from T.
      saccharolyticum. This enzyme is a promising target for future metabolic
      engineering work.

PMID- 29213321
TI  - The effect of coumaryl alcohol incorporation on the structure and composition of
      lignin dehydrogenation polymers.
AB  - Background: Lignin dehydrogenation polymers (DHPs) are polymers generated from
      phenolic precursors for the purpose of studying lignin structure and
      polymerization processes. Methods: Here, DHPs were synthesized using a
      Zutropfverfahren method with horseradish peroxidase and three lignin monomers,
      sinapyl (S), coumaryl (H), and coniferyl (G) alcohols, in the presence of
      hydrogen peroxide. The H monomer was reacted with G and a 1:1 molar mixture of
      S:G monomers at H molar compositions of 0, 5, 10, and 20 mol% to study how the
      presence of the H monomer affected the structure and composition of the recovered
      polymers. Results: At low H concentrations, solid-state NMR spectra suggest that
      the H and G monomers interact to form G:H polymers that have a lower average
      molecular weight than the solely G-based polymer or the G:H polymer produced at
      higher H concentrations. Solid-state NMR and pyrolysis-MBMS analyses suggest that
      at higher H concentrations, the H monomer primarily self-polymerizes to produce
      clusters of H-based polymer that are segregated from clusters of G- or S:G-based
      polymers. Thioacidolysis generally showed higher recoveries of thioethylated
      products from S:G or S:G:H polymers made with higher H content, indicating an
      increase in the linear ether linkages. Conclusions: Overall, the experimental
      results support theoretical predictions for the reactivity and structural
      influences of the H monomer on the formation of lignin-like polymers.

PMID- 29213322
TI  - Deletion of the hfsB gene increases ethanol production in Thermoanaerobacterium
      saccharolyticum and several other thermophilic anaerobic bacteria.
AB  - Background: With the discovery of interspecies hydrogen transfer in the late
      1960s (Bryant et al. in Arch Microbiol 59:20-31, 1967), it was shown that
      reducing the partial pressure of hydrogen could cause mixed acid fermenting
      organisms to produce acetate at the expense of ethanol. Hydrogen and ethanol are
      both more reduced than glucose. Thus there is a tradeoff between production of
      these compounds imposed by electron balancing requirements; however, the
      mechanism is not fully known. Results: Deletion of the hfsA or B subunits
      resulted in a roughly 1.8-fold increase in ethanol yield. The increase in ethanol
      production appears to be associated with an increase in alcohol dehydrogenase
      activity, which appears to be due, at least in part, to increased expression of
      the adhE gene, and may suggest a regulatory linkage between hfsB and adhE. We
      studied this system most intensively in the organism Thermoanaerobacterium
      saccharolyticum; however, deletion of hfsB also increases ethanol production in
      other thermophilic bacteria suggesting that this could be used as a general
      technique for engineering thermophilic bacteria for improved ethanol production
      in organisms with hfs-type hydrogenases. Conclusion: Since its discovery by Shaw
      et al. (JAMA 191:6457-64, 2009), the hfs hydrogenase has been suspected to act as
      a regulator due to the presence of a PAS domain. We provide additional support
      for the presence of a regulatory phenomenon. In addition, we find a practical
      application for this scientific insight, namely increasing ethanol yield in
      strains that are of interest for ethanol production from cellulose or
      hemicellulose. In two of these organisms (T. xylanolyticum and T.
      thermosaccharolyticum), the ethanol yields are the highest reported to date.

PMID- 29213323
TI  - Defined tetra-allelic gene disruption of the 4-coumarate:coenzyme A ligase 1
      (Pv4CL1) gene by CRISPR/Cas9 in switchgrass results in lignin reduction and
      improved sugar release.
AB  - Background: The development of genome editing technologies offers new prospects
      in improving bioenergy crops like switchgrass (Panicum virgatum). Switchgrass is
      an outcrossing species with an allotetraploid genome (2n = 4x = 36), a complexity
      which forms an impediment to generating homozygous knock-out plants. Lignin, a
      major component of the plant cell wall and a contributor to cellulosic
      feedstock's recalcitrance to decomposition, stands as a barrier to efficient
      biofuel production by limiting enzyme access to cell wall polymers during the
      fermentation process. Results: We developed a CRISPR/Cas9 genome editing system
      in switchgrass to target a key enzyme involved in the early steps of monolignol
      biosynthesis, 4-Coumarate:coenzyme A ligase (4CL). Three 4CL genes, Pv4CL1,
      Pv4CL2, and Pv4CL3, were identified in switchgrass. Expression analysis revealed
      that Pv4CL1 transcripts were more abundant in the stem than in the leaf, while
      Pv4CL2 transcripts were barely detectable and Pv4CL3 was mainly expressed in the
      leaf. Pv4CL1 was selected as the target for CRISPR/Cas9 editing because of its
      preferential expression in highly lignified stem tissues. Specific guide RNA was
      constructed to target Pv4CL1. After introducing the construct into switchgrass
      calli, 39 transgenic plants were regenerated. Using two rounds of PCR screening
      and sequencing, four plants were confirmed to have tetra-allelic mutations
      simultaneously. The Pv4CL1 knock-out plants had reduced cell wall thickness, an 8
      30% reduction in total lignin content, a 7-11% increase in glucose release, and a
      23-32% increase in xylose release. Conclusion: This study established a
      successful CRISPR/Cas9 system in switchgrass with mutation efficiency reaching
      10%. The system allows the precise targeting of the selected Pv4CL1 gene to
      create switchgrass knock-out mutant plants with decreased lignin content and
      reduced recalcitrance.

PMID- 29213324
TI  - Progress in understanding and overcoming biomass recalcitrance: a BioEnergy
      Science Center (BESC) perspective.
AB  - The DOE BioEnergy Science Center has operated as a virtual center with multiple
      partners for a decade targeting overcoming biomass recalcitrance. BESC has
      redefined biomass recalcitrance from an observable phenotype to a better
      understood and manipulatable fundamental and operational property. These
      manipulations are the result of deeper biological understanding and can be
      combined with other advanced biotechnology improvements in biomass conversion to
      improve bioenergy processes and markets. This article provides an overview of key
      accomplishments in overcoming recalcitrance via better plants, better microbes,
      and better tools and combinations. A perspective on the aspects of successful
      center operation is presented.

PMID- 29213326
TI  - Correction to: Identification and characterization of a galacturonic acid
      transporter from Neurospora crassa and its application for Saccharomyces
      cerevisiae fermentation processes.
AB  - [This corrects the article DOI: 10.1186/1754-6834-7-20.].

PMID- 29213325
TI  - Designer biomass for next-generation biorefineries: leveraging recent insights
      into xylan structure and biosynthesis.
AB  - Xylans are the most abundant noncellulosic polysaccharides in lignified secondary
      cell walls of woody dicots and in both primary and secondary cell walls of
      grasses. These polysaccharides, which comprise 20-35% of terrestrial biomass,
      present major challenges for the efficient microbial bioconversion of
      lignocellulosic feedstocks to fuels and other value-added products. Xylans play a
      significant role in the recalcitrance of biomass to degradation, and their
      bioconversion requires metabolic pathways that are distinct from those used to
      metabolize cellulose. In this review, we discuss the key differences in the
      structural features of xylans across diverse plant species, how these features
      affect their interactions with cellulose and lignin, and recent developments in
      understanding their biosynthesis. In particular, we focus on how the combined
      structural and biosynthetic knowledge can be used as a basis for biomass
      engineering aimed at developing crops that are better suited as feedstocks for
      the bioconversion industry.

PMID- 29213327
TI  - Green route to synthesis of valuable chemical 6-hydroxynicotine from nicotine in
      tobacco wastes using genetically engineered Agrobacterium tumefaciens S33.
AB  - Background: Tobacco is widely planted as an important nonfood economic crop
      throughout the world, and large amounts of tobacco wastes are generated during
      the tobacco manufacturing process. Tobacco and its wastes contain high nicotine
      content. This issue has become a major concern for health and environments due to
      its toxicity and complex physiological effects. The microbial transformation of
      nicotine into valuable functionalized pyridine compounds is a promising way to
      utilize tobacco and its wastes as a potential biomass resource. Agrobacterium
      tumefaciens S33 is able to degrade nicotine via a novel hybrid of the pyridine
      and pyrrolidine pathways, in which several intermediates, such as 6
      hydroxynicotine, can be used as renewable precursors to synthesize drugs and
      insecticides. This provides an opportunity to produce valuable chemical 6
      hydroxynicotine from nicotine via biocatalysis using strain S33. Results: To
      accumulate the intermediate 6-hydroxynicotine, we firstly identified the key
      enzyme decomposing 6-hydroxynicotine, named 6-hydroxynicotine oxidase, and then
      disrupted its encoding gene in A. tumefaciens S33. With the whole cells of the
      mutant as a biocatalyst, we tested the possibility to produce 6-hydroxynicotine
      from the nicotine of tobacco and its wastes and optimized the reaction
      conditions. At 30  degrees C and pH 7.0, nicotine could be efficiently
      transformed into 6-hydroxynicotine by the whole cells cultivated with
      glucose/ammonium/6-hydroxy-3-succinoylpyridine medium. The molar conversion and
      the specific catalytic rate reached approximately 98% and 1.01 g 6
      hydroxynicotine h-1 g-1 dry cells, respectively. The product could be purified
      easily by dichloromethane extraction with a recovery of 76.8%, and was further
      confirmed by UV spectroscopy, mass spectroscopy, and NMR analysis. Conclusions:
      We successfully developed a novel biocatalytic route to 6-hydroxynicotine from
      nicotine by blocking the nicotine catabolic pathway via gene disruption, which
      provides an alternative green strategy to utilize tobacco and its wastes as a
      biomass resource by converting nicotine into valuable hydroxylated-pyridine
      compounds.

PMID- 29213328
TI  - The transcription factors Hsf1 and Msn2 of thermotolerant Kluyveromyces marxianus
      promote cell growth and ethanol fermentation of Saccharomyces cerevisiae at high
      temperatures.
AB  - Background: High temperature inhibits cell growth and ethanol fermentation of
      Saccharomyces cerevisiae. As a complex phenotype, thermotolerance usually
      involves synergistic actions of many genes, thereby being difficult to engineer.
      The overexpression of either endogenous or exogenous stress-related transcription
      factor genes in yeasts was found to be able to improve relevant stress tolerance
      of the hosts. Results: To increase ethanol yield of high-temperature
      fermentation, we constructed a series of strains of S. cerevisiae by expressing 8
      transcription factor genes from S. cerevisiae and 7 transcription factor genes
      from thermotolerant K. marxianus in S. cerevisiae. The results of growth curve
      measurements and spotting test show that KmHsf1 and KmMsn2 can enhance cell
      growth of S. cerevisiae at 40-42  degrees C. According to the results of batch
      fermentation at 43  degrees C with an initial glucose concentration of 104.8 g/l,
      the fermentation broths of KmHSF1 and KmMSN2-expressing strains could reach final
      ethanol concentrations of 27.2 +/- 1.4 and 27.6 +/- 1.2 g/l, respectively, while
      the control strain just produced 18.9 +/- 0.3 g/l ethanol. Transcriptomic
      analysis found that the expression of KmHSF1 and KmMSN2 resulted in 55 (including
      31 up-regulated and 24 down-regulated) and 50 (including 32 up-regulated and 18
      down-regulated) genes with different expression levels, respectively (padj <
      0.05). The results of transcriptomic analysis also reveal that KmHsf1 might
      increase ethanol production by regulating genes related to transporter activity
      to limit excessive ATP consumption and promote the uptake of glucose; while
      KmMsn2 might promote ethanol fermentation by regulating genes associated with
      glucose metabolic process and glycolysis/gluconeogenesis. In addition, KmMsn2
      might also help to cope with high temperature by regulating genes associated with
      lipid metabolism to change the membrane fluidity. Conclusions: The transcription
      factors KmHsf1 and KmMsn2 of thermotolerant K. marxianus can promote both cell
      growth and ethanol fermentation of S. cerevisiae at high temperatures. Different
      mechanisms of KmHsf1 and KmMsn2 in promoting high-temperature ethanol
      fermentation of S. cerevisiae were revealed by transcriptomic analysis.

PMID- 29213329
TI  - Oxygen-radical pretreatment promotes cellulose degradation by cellulolytic
      enzymes.
AB  - Background: The efficiency of cellulolytic enzymes is important in industrial
      biorefinery processes, including biofuel production. Chemical methods, such as
      alkali pretreatment, have been extensively studied and demonstrated as effective
      for breaking recalcitrant lignocellulose structures. However, these methods have
      a detrimental effect on the environment. In addition, utilization of these
      chemicals requires alkali- or acid-resistant equipment and a neutralization step.
      Results: Here, a radical generator based on non-thermal atmospheric pressure
      plasma technology was developed and tested to determine whether oxygen-radical
      pretreatment enhances cellulolytic activity. Our results showed that the
      viscosity of carboxymethyl cellulose (CMC) solutions was reduced in a time
      dependent manner by oxygen-radical pretreatment using the radical generator.
      Compared with non-pretreated CMC, oxygen-radical pretreatment of CMC
      significantly increased the production of reducing sugars in culture supernatant
      containing various cellulases from Phanerochaete chrysosporium. The production of
      reducing sugar from oxygen-radical-pretreated CMC by commercially available
      cellobiohydrolases I and II was 1.7- and 1.6-fold higher, respectively, than
      those from non-pretreated and oxygen-gas-pretreated CMC. Moreover, the amount of
      reducing sugar from oxygen-radical-pretreated wheat straw was 1.8-fold larger
      than those from non-pretreated and oxygen-gas-pretreated wheat straw.
      Conclusions: Oxygen-radical pretreatment of CMC and wheat straw enhanced the
      degradation of cellulose by reducing- and non-reducing-end cellulases in the
      supernatant of a culture of the white-rot fungus P. chrysosporium. These findings
      indicated that oxygen-radical pretreatment of plant biomass offers great promise
      for improvements in lignocellulose-deconstruction processes.

PMID- 29213330
TI  - Renewable synthesis of n-butyraldehyde from glucose by engineered Escherichia
      coli.
AB  - Background: n-Butyraldehyde is a high-production volume chemical produced
      exclusively from hydroformylation of propylene. It is a versatile chemical used
      in the synthesis of diverse C4-C8 alcohols, carboxylic acids, esters, and amines.
      Its high demand and broad applications make it an ideal chemical to be produced
      from biomass. Results: An Escherichia coli strain was engineered to produce n
      butyraldehyde directly from glucose by expressing a modified Clostridium CoA
      dependent n-butanol production pathway with mono-functional Coenzyme A-acylating
      aldehyde dehydrogenase (Aldh) instead of the natural bifunctional
      aldehyde/alcohol dehydrogenase. Aldh from Clostridium beijerinckii outperformed
      the other tested homologues. However, the presence of native alcohol
      dehydrogenase led to spontaneous conversion of n-butyraldehyde to n-butanol. This
      problem was addressed by knocking out native E. coli alcohol dehydrogenases,
      significantly improving the butyraldehyde-to-butanol ratio. This ratio was
      further increased reducing media complexity from Terrific broth to M9 media
      containing 2% yeast extract. To increase production titer, in situ liquid-liquid
      extraction using dodecane and oleyl alcohol was investigated. Results showed
      oleyl alcohol as a better extractant, increasing the titer of n-butyraldehyde
      produced to 630 mg/L. Conclusion: This study demonstrated n-butyraldehyde
      production from glucose. Through sequential strain and condition optimizations,
      butyraldehyde-to-butanol ratio was improved significantly compared to the parent
      strain. Results from this work may serve as a basis for further development of
      renewable n-butyraldehyde production.

PMID- 29213332
TI  - Artificial intelligence: more human with human.

PMID- 29213331
TI  - Noninvasive prenatal diagnosis of fetal aneuploidy by circulating fetal nucleated
      red blood cells and extravillous trophoblasts using silicon-based nanostructured
      microfluidics.
AB  - Background: Noninvasive prenatal testing (NIPT) based on cell-free DNA in
      maternal circulation has been accepted worldwide by the clinical community since
      2011 but limitations, such as maternal malignancy and fetoplacental mosaicism,
      preclude its full replacement of invasive prenatal diagnosis. We present a novel
      silicon-based nanostructured microfluidics platform named as "Cell RevealTM" to
      demonstrate the feasibility of capturing circulating fetal nucleated red blood
      cells (fnRBC) and extravillous cytotrophoblasts (EVT) for cell-based noninvasive
      prenatal diagnosis (cbNIPD). Methods: The "Cell RevealTM" system is a silicon
      based, nanostructured microfluidics using immunoaffinity to capture the
      trophoblasts and the nucleated RBC (nRBC) with specific antibodies. The automated
      computer analysis software was used to identify the targeted cells through
      additional immunostaining of the corresponding antigens. The identified cells
      were retrieved for whole genome amplification for subsequent investigations by
      micromanipulation in one microchip, and left in situ for subsequent fluorescence
      in situ hybridization (FISH) in another microchip. When validation, bloods from
      pregnant women (n = 24) at gestational age 11-13+6 weeks were enrolled. When
      verification, bloods from pregnant women (n = 5) receiving chorionic villus
      sampling or amniocentesis at gestation age 11+4-21 weeks with an aneuploid or
      euploid fetus were enrolled, followed by genetic analyses using FISH, short
      tandem repeat (STR) analyses, array comparative genomic hybridization, and next
      generation sequencing, in which the laboratory is blind to the fetal genetic
      complement. Results: The numbers of captured targeted cells were 1-44 nRBC/2 ml
      and 1-32 EVT/2 ml in the validation group. The genetic investigations performed
      in the verification group confirmed the captured cells to be fetal origin. In
      every 8 ml of the maternal blood being blindly tested, both fnRBC and EVT were
      always captured. The numbers of captured fetal cells were 14-22 fnRBC/4 ml and 1
      44 EVT/4 ml of maternal blood. Conclusions: This report is one of the first few
      to verify the capture of fnRBC in addition to EVT. The scalability of our
      automated system made us one step closer toward the goal of in vitro diagnostics.

PMID- 29213333
TI  - Comparative genomic analysis of Clostridium difficile ribotype 027 strains
      including the newly sequenced strain NCKUH-21 isolated from a patient in Taiwan.
AB  - Background: Clostridium difficile is a Gram-positive anaerobe and the leading
      cause of antibiotic-associated diarrhea worldwide. The emergence of ribotype 027
      (RT027) strains is associated with increased incidence of infection and
      mortality. To further understand the relationship between C. difficile NCKUH-21,
      a RT027 strain isolated from a patient in Taiwan, and other RT027 strains, we
      performed whole-genome shotgun sequencing on NCKUH-21 and comparative genomic
      analyses. Results: The genome size, G+C content, and gene number for the NCKUH-21
      strain were determined to be similar to those for other C. difficile strains. The
      core genome phylogeny indicated that the five RT027 strains R20291, CD196, NCKUH
      21, BI1, and 2007855 formed a clade. A pathogenicity locus, tcdR-tcdB-tcdE-orf
      tcdA-tcdC, was conserved in the genome. A genomic region highly similar to the
      Clostridium phage [Formula: see text]CD38-2 was present in the NCKUH-21 strain
      but absent in the other RT027 strains and designated as the prophage [Formula:
      see text]NCKUH-21. The prophage [Formula: see text]NCKUH-21 genes were
      significantly higher in G+C content than the other genes in the NCKUH-21 genome,
      indicating that the prophage does not match the base composition of the host
      genome. Conclusions: This is the first whole-genome analysis of a RT027 C.
      difficile strain isolated from Taiwan. Due to the high identity with [Formula:
      see text]CD38-2, the prophage identified in the NCKUH-21 genome has the potential
      to regulate toxin production. These results provide important information for
      understanding the pathogenicity of RT027 C. difficile in Taiwan.

PMID- 29213334
TI  - Measuring the Empowerment of International Organizations: The Evolution of
      Financial and Staff Capabilities.
AB  - International organizations' (IOs) power in shaping global governance outcomes is
      not only determined by the formal delegation of tasks and issue areas but also by
      the necessary capabilities to fulfill these tasks. Yet, extant research on the
      delegation of power to IOs gives few insights into the financial and staff
      capabilities of IOs and focuses mainly on the formal rules that specify IOs'
      tasks and issue scope. To address these limitations, this paper makes three
      contributions. First, we propose a more encompassing concept of IO power which
      incorporates three principal components: tasks, issue scope, and capabilities.
      Second, we introduce a new concept - IO empowerment (IOE) - which encapsulates
      formal and informal changes in IO power over time. Third, we introduce a novel
      dataset on IO capabilities, which measures the formal rules governing IO staff
      and financial resources as well as the actual capabilities available to six well
      known IOs over 65 years. These original data show that capabilities vary not only
      across IOs but also over time.

PMID- 29213335
TI  - Liraglutide attenuates atherosclerosis via inhibiting ER-induced macrophage
      derived microvesicles production in T2DM rats.
AB  - Background: We investigated the effects of liraglutide on the formation and
      progression of atherosclerosis in type 2 diabetes mellitus (T2DM) rats. Methods:
      Sprague-Dawley rats were divided into control group, diabetes group and
      liraglutide treated group. The T2DM rats model with atherosclerosis were induced
      by high fat diet followed small dosage streptozotocin injection. Body weight and
      blood glucose levels were monitored once a week for 3 months and then the rats
      were sacrificed.Peripheral blood and aorta tissues were collected for further
      biochemical and pathological estimation respectively. Moreover,
      immunohistochemistry staining was used to detect the infiltration of macrophages
      and cell apoptosis in tissue samples. The amount of microvesicles of
      atherosclerotic plaques was determined by ELISA. Western blot was applied to
      detect the protein expressions of CHOP, GRP78 and caspase-3 in tissue samples.
      The mRNA expressions of SREBP-1c and FAS were detected by RT-PCR. Results: The
      rat model of diabetic atherosclerosis was established successfully. Compared with
      the control group, glucose, triglycerides, total cholesterol, AST, ALT, BUN,
      fasting insulin and homeostatic model assessment insulin resistance levels in
      peripheral blood were significantly increased in the diabetes group. While, these
      indicators in the liraglutide group were significantly lower than that in the
      diabetes group. Moreover, the atherosclerotic plaques were observed in the rats
      of diabetes group but not remarkable in the liraglutide group. The ratio between
      aorta intima and media thickness was significantly greater in the diabetes group
      than that in the liraglutide group. Compared with the diabetes group, the
      infiltration and apoptosis of macrophages were milder in the liraglutide group.
      The expressions of CD68, caspase-3, CHOP and GRP78 in aorta tissue samples were
      significantly downregulated in the liraglutide group than that in the diabetes
      group. Furthermore, the microvesicles of aorta tissues in the liraglutide group
      were significantly decreased than that in the diabetes group. The mRNA
      expressions of SREBP-1c and FAS were lower in the liraglutide group than that in
      the diabetes group. Conclusion: Liraglutide attenuates diabetic atherosclerosis
      by inhibition of ER stress and subsequent macrophage apoptosis and microvesicles
      production in T2DM rats.

PMID- 29213336
TI  - Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal
      weight individuals.
AB  - Background: The interplay between adiponectin and resistin, the two adipokines of
      opposite effects, may determine the metabolic profile of obese individuals and
      development of obesity-related complications. The current study was conducted to
      assess how adiponectin/resistin interplay in sera and adipose tissues may
      influence the metabolic profile of obese and normal-weight subjects. Methods:
      Concentrations of adiponectin and resistin were measured on protein level by
      immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass
      index > 40 kg/m2) and 28 normal-weight (body mass index 20-24.9 kg/m2)
      individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin
      and resistin, respectively) was assessed on mRNA level by real-time PCR. Results:
      ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower,
      while RETN mRNA (P = 0.0338) and resistin (P < 0.0001)-higher in subcutaneous
      adipose tissues of obese subjects. ADIPOQ and RETN mRNA levels did not correlate
      with protein concentrations in the investigated adipose tissues. In obesity
      adiponectin serum concentrations correlated positively with ADIPOQ mRNA in
      subcutaneous adipose tissue (P = 0.005) and negatively with protein levels in
      visceral adipose tissue (P = 0.001). Obesity was associated with higher
      adiponectin-resistin index value in sera (P < 0.0001) and decreased in
      subcutaneous adipose tissue (P < 0.001), but only adiponectin-resistin index
      measured in sera was significantly higher in obese with the metabolic syndrome (P
      = 0.04). Conclusions: Obesity affects synthesis of adiponectin and resistin
      mainly in subcutaneous adipose tissue. The adiponectin-resistin index assessed in
      the adipose tissues has a different prognostic value compared to the adiponectin
      resistin index in serum and does not reflect a metabolic risk in obese
      individuals.

PMID- 29213337
TI  - Effectiveness of long-term treatment with SGLT2 inhibitors: real-world evidence
      from a specialized diabetes center.
AB  - Background: Diabetes is a progressive disease needing multiple drugs for
      achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2
      inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several
      beneficial effects. However, the long-term effectiveness in clinical practice and
      safety data of SGLT2 inhibitors is limited, especially in Asian patients. To
      better understand the effectiveness of SGLT2i in clinical practice, we conducted
      a retrospective evaluation of patients with diabetes on SGLT2i. Methods: This
      retrospective observational study uses data of patients with diabetes who had
      been prescribed SGLT2i and continued to use at least 6 months at Theptarin
      Hospital, Bangkok. The characteristics of patients, changes in glycemic control
      and body weight at 3, 6, 12, 18, 24 months and the last follow-up were evaluated.
      Results: A total of 189 patients with diabetes (females 50.3%, mean age 59.9 +/-
      12.3 years, T2DM 97.3%, duration of diabetes 16.3 +/- 9.2 years, baseline BMI
      29.9 +/- 6.1 kg/m2, baseline HbA1c 8.8 +/- 1.6%) were prescribed SGLT2i during
      the study period. At the time of first SGLT2i prescription, 80.4% used three or
      more other anti-diabetic agents concomitantly and 34.6% used insulin
      concomitantly. 151 patients who continue to use at least 6 months were included
      in analysis. At the last follow-up (median time 16 months), overall median HbA1c
      reduction and weight reduction were 1.0% and 1.5 kg, respectively. While glycemic
      control could maintain up to 18 months, weight loss gradually rebounded after the
      first 6 months and then backed to baseline body weight at 18 months (78.2 +/-
      18.0 kg vs. 78.0 +/- 17.8, p value = 0.324). The incidence of adverse drug
      reactions of special interest (polyuria, volume depletion-related events, urinary
      tract infection, genital infection, and hypoglycemia) was 2.1, 1.6, 2.1, 2.6, and
      7.9%, respectively. Discussion: This real-world study confirmed long-term
      durability of glycemic control with SGLT2i in not only monotherapy, but also add
      on studies with other oral anti-diabetic drugs and/or insulin treatment. However,
      weight loss became evident early after 6 weeks then reached slightly rebounds
      after 24 weeks until the end of follow-up. Further studies should be done towards
      a better understanding of treatment with SGLT2i in routine clinical practice.

PMID- 29213338
TI  - Particle therapy and nanomedicine: state of art and research perspectives.
AB  - Cancer radiation therapy with charged particle beams, called particle therapy, is
      a new therapeutic treatment presenting major advantages when compared to
      conventional radiotherapy. Because ions have specific ballistic properties and a
      higher biological effectiveness, they are superior to x-rays. Numerous medical
      centres are starting in the world using mostly protons but also carbon ions as
      medical beams. Several investigations are attempting to reduce the cost/benefit
      ratio and enlarge the range of therapeutic indications. A major limitation of
      particle therapy is the presence of low but significant damage induced in healthy
      tissues located at the entrance of the ion track prior to reaching the tumour. It
      is thus a major challenge to improve the targeting of the tumours, concentrating
      radiation effects in the malignance. A novel strategy, based on the addition of
      nanoparticles targeting the tumour, was suggested over a decade ago to improve
      the performance of conventional photon therapy. Recently, similar developments
      have emerged for particle therapy and the amount of research is now exploding. In
      this paper, we review the experimental results, as well as theoretical and
      simulation studies that shed light in the promising outcomes of this strategy and
      in the underpinning mechanisms. Several experiments provide consistent evidence
      of significant enhancement of ion radiation effects in the presence of
      nanoparticles. In view of implementing this strategy for cancer treatment,
      simulation studies have begun to establish the rationale and the specificity of
      this effect. In addition, these studies will help to outline a list of possible
      mechanisms and to predict the impact of ion beams and nanoparticle
      characteristics. Many questions remain unsolved, but the findings of these first
      studies are encouraging and open new challenges. After summarizing the main
      results in the field, we propose a roadmap to pursue future research with the aim
      to strengthen the potential interplay between particle therapy and nanomedicine.

PMID- 29213340
TI  - The Sense of Commitment in Human-Robot Interaction.
AB  - The sense of commitment is a fundamental building block of human social life. By
      generating and/or stabilizing expectations about contributions that individual
      agents will make to the goals of other agents or to shared goals, a sense of
      commitment can facilitate the planning and coordination of actions involving
      multiple agents. Moreover, it can also increase individual agents' motivation to
      contribute to other agents' goals or to shared goals, as well as their
      willingness to rely on other agents' contributions. In this paper, we provide a
      starting point for designing robots that exhibit and/or elicit a sense of
      commitment. We identify several challenges that such a project would likely
      confront, and consider possibilities for meeting these challenges.

PMID- 29213339
TI  - Comparison of quantification algorithms for circulating cell-free DNA methylation
      biomarkers in blood plasma from cancer patients.
AB  - Background: SHOX2 and SEPT9 methylation in circulating cell-free DNA (ccfDNA) in
      blood are established powerful and clinically valuable biomarkers for diagnosis,
      staging, prognosis, and monitoring of cancer patients. The aim of the present
      study was to evaluate different quantification algorithms (relative
      quantification, absolute quantification, quasi-digital PCR) with regard to their
      clinical performance. Methods: Methylation analyses were performed in a training
      cohort (141 patients with head and neck squamous cell carcinoma [HNSCC], 170
      control cases) and a testing cohort (137 HNSCC cases, 102 controls). DNA was
      extracted from plasma samples, bisulfite-converted, and analyzed via quantitative
      real-time PCR. SHOX2 and SEPT9 methylations were assessed separately and as panel
      [mean SEPT9/SHOX2 ] using the DeltaCT method for absolute quantification and the
      DeltaDeltaCT-method for relative quantification. Quasi-digital PCR was defined as
      the number of amplification-positive PCR replicates. The diagnostic (sensitivity,
      specificity, area under the curve (AUC) of the receiver operating characteristic
      (ROC)) and prognostic accuracy (hazard ratio (HR) from Cox regression) were
      evaluated. Results: Sporadic methylation in control samples necessitated the
      introduction of cutoffs resulting in 61-63% sensitivity/90-92% specificity
      (SEPT9/training), 53-57% sensitivity/87-90% specificity (SHOX2/training), and 64
      65% sensitivity/90-91% specificity (mean SEPT9/SHOX2 /training). Results were
      confirmed in a testing cohort with 54-56% sensitivity/88-90% specificity
      (SEPT9/testing), 43-48% sensitivity/93-95% specificity (SHOX2/testing), and 49
      58% sensitivity/88-94% specificity (mean SEPT9/SHOX2 /testing). All algorithms
      showed comparable cutoff-independent diagnostic accuracy with largely overlapping
      95% confidence intervals (SEPT9: AUCtraining = 0.79-0.80; AUCtesting = 0.74-0.75;
      SHOX2: AUCtraining = 0.78-0.81, AUCtesting = 0.77-0.79; mean SEPT9/SHOX2 :
      AUCtraining = 0.81-0.84, AUCtesting = 0.80). The accurate prediction of overall
      survival was possible with all three algorithms (training cohort: HR SEPT9  =
      1.23-1.90, HR SHOX2  = 1.14-1.85, HRmeanSEPT9/SHOX2  =1.19-1.89 ; testing cohort:
      HR SEPT9  =1.22-1.67, HR SHOX2  = 1.15-1.71, HRmeanSEPT9/SHOX2  = 1.12-1.77).
      Conclusion: The concordant clinical performance based on different quantification
      algorithms allows for the application of various diagnostic platforms for the
      analysis of ccfDNA methylation biomarkers.

PMID- 29213341
TI  - CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3'
      5' exonuclease activity and contribute to protection against oxidative stress.
AB  - Apurinic/apyrimidinic (AP) sites are one of the most frequent DNA lesions. AP
      sites inhibit transcription and DNA replication, and induce cell death. AP
      endonucleases are key enzymes in AP site repair. Several types of AP
      endonucleases have been reported, such as AP endonuclease 2 (APEX2) and ribosomal
      protein P0 (P0). However, it is not known how the functions and roles differ
      among AP endonucleases. To clarify the difference of roles among AP
      endonucleases, we conducted biochemical analysis focused on APEX2 and P0
      homologues in Ciona intestinalis. Amino acid sequence analysis suggested that
      CiAPEX2 and CiP0 are AP endonuclease homologues. Although we could not detect AP
      endonuclease or 3'-phosphodiesterase activity, these two purified proteins
      exhibited 3'-5' exonuclease activity. This 3'-5' exonuclease activity was
      sensitive to ethylenediaminetetraacetic acid (EDTA), and the efficiency of this
      activity was influenced by the 3'-terminus of substrate DNA. Both CiAPEX2 and
      CiP0 degraded not only a 5'-protruding DNA end, but also nicked DNA, which is
      generated through AP endonuclease 1 (APEX1) cleavage. These two genes partially
      complemented the growth rate of AP endonuclease-deficient Escherichia coli
      treated with hydrogen peroxide. These results indicate that 3'-5' exonuclease
      activity is an evolutionarily conserved enzymatic activity of APEX2 and P0
      homologues and this enzymatic activity may be important for AP endonucleases.

PMID- 29213342
TI  - Unique molecular mechanisms for maintenance and alteration of genetic information
      in the budding yeast Saccharomyces cerevisiae.
AB  - The high-fidelity transmission of genetic information is crucial for the survival
      of organisms, the cells of which have the ability to protect DNA against
      endogenous and environmental agents, including reactive oxygen species (ROS),
      ionizing radiation, and various chemical compounds. The basis of protection
      mechanisms has been evolutionarily conserved from yeast to humans; however, each
      organism often has a specialized mode of regulation that uses different sets of
      machineries, particularly in lower eukaryotes. The divergence of molecular
      mechanisms among related organisms has provided insights into the evolution of
      cellular machineries to a higher architecture. Uncommon characteristics of
      machineries may also contribute to the development of new applications such as
      drugs with novel mechanisms of action. In contrast to the cellular properties for
      maintaining genetic information, living organisms, particularly microbes,
      inevitably undergo genetic alterations in order to adapt to environmental
      conditions. The maintenance and alteration of genetic information may be
      inextricably linked to each other. In this review, we describe recent findings on
      the unconventional molecular mechanisms of DNA damage response and DNA double
      strand break (DSB) repair in the budding yeast Saccharomyces cerevisiae. We also
      introduce our previous research on genetic and phenotypic instabilities observed
      in a clonal population of clinically-derived S. cerevisiae. The molecular
      mechanisms of this case were associated with mutations to generate tyrosine
      inserting tRNA-Tyr ochre suppressors and the position effects of mutation
      frequencies among eight tRNA-Tyr loci dispersed in the genome. Phenotypic
      variations among different strain backgrounds have also been observed by another
      type of nonsense suppressor, the aberrant form of the translation termination
      factor. Nonsense suppressors are considered to be responsible for the genome-wide
      translational readthrough of termination codons, including natural nonsense
      codons. The nonsense suppressor-mediated acquisition of phenotypic variations may
      be advantageous for adaptation to environmental conditions and survival during
      evolution.

PMID- 29213343
TI  - Exome sequencing characterizes the somatic mutation spectrum of early serrated
      lesions in a patient with serrated polyposis syndrome (SPS).
AB  - Background: Serrated or Hyperplastic Polyposis Syndrome (SPS, HPS) is a yet
      poorly defined colorectal cancer (CRC) predisposition characterised by the
      occurrence of multiple and/or large serrated polyps throughout the colon. A
      serrated polyp-CRC sequence (serrated pathway) of CRC formation has been
      postulated, however, to date only few molecular signatures of serrated neoplasia
      (BRAF, KRAS, RNF43 mutations, CpG Island Methylation, MSI) have been described in
      a subset of SPS patients and neither the etiology of the syndrome nor the
      distinct genetic alterations during tumorigenesis have been identified. Methods:
      To identify somatic point mutations in potential novel candidate genes of SPS
      associated lesions and the involved pathways we performed exome sequencing of
      eleven early serrated polyps obtained from a 41 year-old female patient with
      clinically confirmed SPS. For data filtering and analysis, standard pipelines
      were used. Somatic mutations were identified by comparison with leukocyte DNA and
      were validated by Sanger sequencing. Results: The BRAF p.V600E or KRAS p.G12D
      mutation was identified in six polyps (~50%) and not found in polyps from the
      distal colon. In addition, we found seven unique rare somatic alterations of
      seven different genes in four serrated tumours, all of which are missense
      variants. The variant in ABI3BP and CATSPERB are predicted to be deleterious. No
      established cancer gene or candidate genes related to serrated tumorigenesis were
      affected. Conclusions: Somatic mutations seem to be rare events in early
      hyperplastic and serrated lesions of SPS patients. Neither frequently affected
      genes nor enrichment of specific pathways were observed. Thus, other alterations
      such as non-coding variants or epigenetic changes might be the major driving
      force of tumour progression in SPS.

PMID- 29213345
TI  - The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis
      Centre Approach.
AB  - Purpose of Review: Chronic pulmonary aspergillosis (CPA) is a serious long-term
      fungal disease of the lung with a worldwide prevalence. Treatment of CPA is not
      straightforward given the often-multiple associated co-morbidities, complex
      clinical picture, drug interactions, toxicities and intolerances. Recent
      Findings: First line treatment is oral itraconazole or voriconazole. In the event
      of intolerance or toxicity, patients may be swapped from itraconazole to
      voriconazole or vice versa. In the event of resistance or further intolerance,
      third line treatment with posaconazole could be initiated. In those with pan
      azole resistance, short-term courses of intravenous liposomal amphotericin B or
      micafungin are fourth line therapy, keeping in mind the nephrotoxic effects of
      amphotericin B. Summary: The available evidence for current treatments in CPA is
      limited and based mostly on retrospective cohort studies. There is a real need to
      raise awareness of this devastating disease to enable early treatment as well as
      prospective drug trials and studies to identify potential patient factors that
      correlate with progression, severity and overall outcomes in order to target
      future therapies.

PMID- 29213344
TI  - Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A
      Health Technology Assessment.
AB  - Background: Major depressive disorder and generalized anxiety disorder are among
      the most commonly diagnosed mental illnesses in Canada; both are associated with
      a high societal and economic burden. Treatment for major depressive disorder and
      generalized anxiety disorder consists of pharmacological and psychological
      interventions. Three commonly used psychological interventions are cognitive
      behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The
      objectives of this report were to assess the effectiveness and safety of these
      types of therapy for the treatment of adults with major depressive disorder
      and/or generalized anxiety disorder, to assess the cost-effectiveness of
      structured psychotherapy (CBT or interpersonal therapy), to calculate the budget
      impact of publicly funding structured psychotherapy, and to gain a greater
      understanding of the experiences of people with major depressive disorder and/or
      generalized anxiety disorder. Methods: We performed a literature search on
      October 27, 2016, for systematic reviews that compared CBT, interpersonal
      therapy, or supportive therapy with usual care, waitlist control, or
      pharmacotherapy in adult outpatients with major depressive disorder and/or
      generalized anxiety disorder. We developed an individual-level state-transition
      probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a
      primary diagnosis of major depressive disorder to determine the cost
      effectiveness of individual or group CBT (as a representative form of structured
      psychotherapy) versus usual care. We also estimated the 5-year budget impact of
      publicly funding structured psychotherapy in Ontario. Finally, we interviewed
      people with major depressive disorder and/or generalized anxiety disorder to
      better understand the impact of their condition on their daily lives and their
      experience with different treatment options, including psychotherapy. Results:
      Interpersonal therapy compared with usual care reduced posttreatment major
      depressive disorder scores (standardized mean difference [SMD]: 0.24, 95%
      confidence interval [CI]: -0.47 to -0.02) and reduced relapse/recurrence in
      patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27
      0.63). Supportive therapy compared with usual care improved major depressive
      disorder scores (SMD: 0.58, 95% CI: 0.45-0.72) and increased posttreatment
      recovery (odds ratio [OR]: 2.71, 95% CI: 1.19-6.16) in patients with major
      depressive disorder. CBT compared with usual care increased response (OR: 1.58,
      95% CI: 1.11-2.26) and recovery (OR: 3.42, 95% CI: 1.98-5.93) in patients with
      major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI:
      0.65-0.87]). For patients with generalized anxiety disorder, CBT improved
      symptoms posttreatment (SMD: 0.80, 95% CI: 0.67-0.93), improved clinical response
      posttreatment (RR: 0.64, 95% CI: 0.55-0.74), and improved quality-of-life scores
      (SMD: 0.44, 95% CI: 0.06-0.82). There was a significant difference in
      posttreatment recovery (OR: 1.98, 95% CI: 1.11-3.54) and mean major depressive
      disorder symptom scores (weighted mean difference: -3.07, 95% CI: -4.69 to -1.45)
      for patients who received individual versus group CBT. Details about the
      providers of psychotherapy were rarely reported in the systematic reviews we
      examined.In the base case probabilistic cost-utility analysis, compared with
      usual care, both group and individual CBT were associated with increased
      survival: 0.11 quality-adjusted life-years (QALYs) (95% credible interval [CrI]:
      0.03-0.22) and 0.12 QALYs (95% CrI: 0.03-0.25), respectively.Group CBT provided
      by nonphysicians was associated with the smallest increase in discounted costs:
      $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT
      provided by nonphysicians, and individual CBT provided by physicians were
      associated with the incremental costs of $1,805 (95% CrI: 65-3,516), $3,168 (95%
      CrI: 889-5,624), and $5,311 (95% CrI: 2,539-8,938), respectively. The
      corresponding incremental cost-effectiveness ratio (ICER) was lowest for group
      CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT
      provided by physicians ($43,443/QALY gained). In the analysis that ranked best
      strategies, individual CBT versus group CBT provided by nonphysicians yielded an
      ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians
      being cost-effective versus usual care was greater than 95% for all willingness
      to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT
      provided by physicians at a threshold of $100,000 per QALY.We estimated that
      adding structured psychotherapy to usual care over the next 5 years would result
      in a net budget impact of $68 million to $529 million, depending on a range of
      factors. We also estimated that to provide structured psychotherapy to all adults
      with major depressive disorder (alone or combined with generalized anxiety
      disorder) in Ontario by 2021, an estimated 500 therapists would be needed to
      provide group therapy, and 2,934 therapists would be needed to provide individual
      therapy.People with major depressive disorder and/or generalized anxiety disorder
      with whom we spoke reported finding psychotherapy effective, but they also
      reported experiencing a large number of barriers that prevented them from finding
      effective psychotherapy in a timely manner. Participants reported wanting more
      freedom to choose the type of psychotherapy they received. Conclusions: Compared
      with usual care, treatment with CBT, interpersonal therapy, or supportive therapy
      significantly reduces depression symptoms posttreatment. CBT significantly
      reduces anxiety symptoms posttreatment in patients with generalized anxiety
      disorder.Compared with usual care, treatment with structured psychotherapy (CBT
      or interpersonal therapy) represents good value for money for adults with major
      depressive disorder and/or generalized anxiety disorder. The most affordable
      option is group structured psychotherapy provided by nonphysicians, with the
      selective use of individual structured psychotherapy provided by nonphysicians or
      physicians for those who would benefit most from it (i.e., patients who are not
      engaging well with or adhering to group therapy).

PMID- 29213346
TI  - Safe Plastic Surgery of the Breast II: Saving Nipple Sensation.
AB  - Background: Since its inception, reduction mammoplasty has matured considerably.
      Primary evolution in clinical research and practice initially focused on
      developing techniques to preserve tissue viability; breast parenchyma, skin, and
      nipple tissue that has expanded to include sensation and erectile function play a
      large role in the physical intimacy of women. Studies regarding primary
      innervation to the nipple are few and often contradictory. Our past anatomical
      study demonstrated that primary innervation to the nipple to come from the
      lateral branch of the fourth intercostal nerve. We propose an unsafe zone in
      which dissection during reduction mammoplasty ought to be avoided to preserve
      nipple sensation. Objective: To identify the trajectory of innervation to the
      nipple and translate these findings to the clinical setting so as to preserve
      nipple sensation. Methods: Eighty-six patients underwent reduction mammoplasty
      using the Wise pattern inferior pedicle (n = 72), vertical Hall-Findlay
      superomedial pedicle (n = 11), and Drape pattern inferior pedicle (n = 3).
      Aggressive dissection in the most superficial and deep tissue in the
      inferolateral quadrant of the breast was avoided. Results: All 86 patients
      reported having the same normal sensation to the breast at postoperative
      evaluation. Conclusions: The fourth intercostal nerve provides the major
      innervation to the nipple-areola complex. Avoiding dissection in inferolateral
      quadrant "unsafe zone" of the breast during reduction mammoplasty can reliably
      spare nipple sensation and maximize patient outcomes.

PMID- 29213347
TI  - Restoration of Elbow Flexion in Patients With Complete Traumatic and Obstetric
      Brachial Plexus Injury After Functional Free Gracilis Muscle Transfer: Our
      Experience and Management.
AB  - Background: Functional free gracilis muscle transfer is an operative procedure
      for elbow reconstruction in patients with complete brachial plexus nerve and
      avulsion injuries and in delayed or prolonged nerve denervation, as well as in
      patients with inadequate upper extremity function after primary nerve
      reconstruction. Methods: We retrospectively reviewed our patient records and
      identified 24 patients with complete brachial plexus nerve injury (13 obstetric,
      11 males and 2 females; 11 traumatic, 9 males and 2 females) whose affected arm
      and shoulder were totally paralyzed and their voluntary elbow flexion or the
      biceps function was poor preoperatively (mean M0-1/5 in MRC grade). These
      patients had undergone the functional free gracilis muscle transfer procedure at
      our clinic since 2005. Results: Ninety-two percent of all patients showed
      recovery and improvement. Successful free gracilis muscle transfer is defined as
      antigravity biceps muscle strength of M3-4/5 and higher, which was observed in 16
      (8 obstetric and 8 traumatic) of our 24 patients (67%) in this study at least 1
      year after functional free gracilis muscle transfer. This is statistically
      significant (P < .000001) in comparison with their mean preoperative score (M0
      1/5). There was no improvement in motor level of the biceps muscle (M0/5) in 2
      patients (1 from each group). The donor site of these 24 patients showed no
      deficit in motor and sensory functions. Conclusions: Taken together, a
      significant number (92%) of patients in both obstetric and traumatic brachial
      plexus injury groups had recovery and improvement and most of these patients
      (64%) achieved antigravity and elbow flexion at least 1 year after free gracilis
      muscle transfer at our clinic.

PMID- 29213349
TI  - Oxidants and Redox Signaling: Perspectives in Cancer Therapy, Inflammation, and
      Plasma Medicine.

PMID- 29213348
TI  - Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress
      following Cardiopulmonary Resuscitation.
AB  - Objective: To investigate the protective effect of probucol on induced cardiac
      arrest (CA) rats and possible mechanisms. Methods: Sprague Dawley rats were
      orally administrated with probucol at different dosage or vehicle for 5 days and
      subjected to a CA model by electrical stimulation, followed by cardiopulmonary
      resuscitation (CPR). The return of spontaneous circulation (ROSC) rate,
      antioxidant enzyme activities, and lipid oxidation markers were measured in serum
      and myocardium. Hemodynamic parameters and myocardial functions of animals were
      analyzed. Expression of erythroid-derived 2-like 2 (NFE2L2) and Kelch-like ECH
      associated protein 1 (KEAP1) in the myocardium were examined with
      immunohistochemistry. Results: Probucol treatment significantly increased the
      ROSC rate and survival time of CA-induced rats. After ROSC, levels of oxidation
      specific markers were decreased, while activities of antioxidant enzymes were
      increased significantly in probucol treatment groups. The probucol treatment
      improves hemodynamic parameters and myocardial functions. These parameter changes
      were in a dose-dependent manner. In the probucol treatment groups, the expression
      of KEAP1 was downregulated, while that of NFE2L2 was upregulated significantly.
      Conclusion: In the CA-induced rat model, probucol dose dependently improved the
      ROSC rate, prolonged survival time, alleviated oxidative stress, and improved
      cardiac function. Such protective effects are possibly through regulations of the
      KEAP1-NFE2L2 system.

PMID- 29213350
TI  - Immediate Early Response Gene X-1 (IEX-1) Mediates Ischemic Preconditioning
      Induced Cardioprotection in Rats.
AB  - Reversible myocardial ischemia/reperfusion (I/R) or ischemic preconditioning
      (IPC) is associated with an immediate genomic response; IPC-induced immediate
      early genes are associated with reduced infarct size. Because the immediate early
      response gene X-1 (IEX-1) plays a central role in cell apoptosis, we examine
      whether IEX-1 exerts protective effects against I/R injury. We found that the IEX
      1 mRNA level was increased in the IPC-imposed rat heart. However, it was
      downregulated in the I/R rat heart, which was prevented by in situ IPC. When IEX
      1 was knocked down, the protective effects imposed by IPC were lessened. Local
      gene delivery of Ad-IEX-1 to the left ventricle greatly diminished cardiac
      infarct size and improved systolic functions of I/R hearts in rats. In contrast,
      knocking down IEX-1 expression exacerbates myocardial infarction. Overexpression
      of IEX-1 in neonatal rat cardiomyocytes significantly reduced hypoxia
      reoxygenation-induced intracellular and mitochondrial ROS accumulation and cell
      apoptosis. Furthermore, IPC-induced phosphorylation and particle translocation of
      PKCepsilon were impaired by knocking down IEX-1 in vivo, and overexpressing IEX-1
      showed similar cardioprotection imposed by IPC. Our results demonstrate that IPC
      increases IEX-1 expression, which may promote phosphorylation and particle
      translocation of PKCepsilon and thus reduce intracellular ROS accumulation. These
      beneficial effects reduce cardiomyocyte apoptosis and necrosis to alleviate
      cardiac infarction.

PMID- 29213351
TI  - Spondias purpurea L. (Anacardiaceae): Antioxidant and Antiulcer Activities of the
      Leaf Hexane Extract.
AB  - Spondias purpurea is used in folk medicine to treat diarrhea and diuresis. The
      objective of this study was to evaluate the phytochemical profile and antioxidant
      and antiulcer activities of the hexane extract of the leaves of S. purpurea
      (SpHE). Phytochemical profile was evaluated via thin layer chromatography (TLC)
      and HPLC. SpHE was screened for antioxidant activities using DPPH, ABTS, FRAP,
      and phosphomolybdenum assays. To determine its antiulcer properties, animals were
      pretreated with injured control, lansoprazole, ranitidine, carbenoxolone, or SpHE
      (12.5, 25, and 50 mg/kg) and were screened; acute ulcers were induced by
      HCl/ethanol, absolute ethanol, and nonsteroidal anti-inflammatory drug (NSAID).
      TLC revealed the presence of flavonoids, whereas HPLC analysis showed the
      presence of caffeic acid and epigallocatechin. The phenolic compounds and in
      vitro assays showed antioxidant activity. After gastric ulcer induction by using
      HCl/ethanol, SpHE reduced the area of ulcerative lesions by 82, 91, and 88%,
      respectively. In ethanol, SpHE reduced the area of ulcerative lesions by 77, 93,
      and 92%, respectively. In the NSAID, the percentages of protection were 70, 76,
      and 78%, respectively. SpHE promoted the minimization of ulcers, increased the
      levels of reduced glutathione, and decreased tumor necrosis factor. S. purpurea
      has antioxidant and antiulcer properties.

PMID- 29213352
TI  - Echinacoside Alleviates UVB Irradiation-Mediated Skin Damage via Inhibition of
      Oxidative Stress, DNA Damage, and Apoptosis.
AB  - Ultraviolet B (UVB) irradiation has been known to cause skin damage, which is
      associated with oxidative stress, DNA damage, and apoptosis. Echinacoside is a
      phenylethanoid glycoside isolated from Herba Cistanches, which exhibits strong
      antioxidant activity. In this study, we evaluate the photoprotective effect of
      echinacoside on UVB-induced skin damage and explore the potential molecular
      mechanism. BALB/c mice and HaCaT cells were treated with echinacoside before UVB
      exposure. Histopathological examination was used to evaluate the skin damage.
      Cell viability, lactate dehydrogenase (LDH) levels, antioxidant enzyme
      activities, reactive oxygen species (ROS) generation, DNA damage, and apoptosis
      were measured as well. Western blot was used to measure the expression of related
      proteins. The results revealed that pretreatment of echinacoside ameliorated the
      skin injury; attenuated oxidative stress, DNA damage, and apoptosis caused by UVB
      exposure; and normalized the protein levels of ATR, p53, PIAS3, hnRNP K, PARP,
      and XPA. To summarize, echinacoside is beneficial in the prevention of UVB
      induced DNA damage and apoptosis of the skin in vivo and in vitro.

PMID- 29213353
TI  - Resveratrol Prevents ROS-Induced Apoptosis in High Glucose-Treated Retinal
      Capillary Endothelial Cells via the Activation of AMPK/Sirt1/PGC-1alpha Pathway.
AB  - Resveratrol (RSV) is used as a protective therapy against diabetic retinopathy.
      However, the mechanism(s) underlying this protective effect has not been fully
      elucidated. Bovine retinal capillary endothelial cells (BRECs), an in vitro
      model, were used to investigate the mechanism of RSV. Our results showed that
      high glucose induced significant cellular apoptosis in BRECs, which was
      accompanied by increased intracellular levels of reactive oxygen species (ROS)
      and cleaved caspase-3. The glucose-induced apoptosis and ROS elevation were both
      inhibited by RSV. High glucose was found to decrease the levels of phosphorylated
      AMP-activated protein kinase (p-AMPK), which was accompanied by increased levels
      of Sirt1 and PGC-1alpha. These changes were reversed by RSV. We also demonstrated
      that AMPK regulates the modulations of Sirt1 and PGC-1alpha using specific
      inhibitors of AMPK and Sirt1 and small interfering RNAs of PGC-1alpha. In
      summary, the current study demonstrates that RSV is effective against high
      glucose-induced cellular apoptosis and its action is exerted via the inhibition
      of ROS/AMPK/Sirt1/PGC-1alpha pathway.

PMID- 29213355
TI  - Draft genome sequence of Venturia carpophila, the causal agent of peach scab.
AB  - Venturia carpophila causes peach scab, a disease that renders peach (Prunus
      persica) fruit unmarketable. We report a high-quality draft genome sequence (36.9
      Mb) of V. carpophila from an isolate collected from a peach tree in central
      Georgia in the United States. The genome annotation is described and a
      phylogenetic analysis of the pathogen is presented. The genome sequence will be a
      useful resource for various studies on the pathogen, including the biology and
      ecology, taxonomy and phylogeny, host interaction and coevolution, isolation and
      characterization of genes of interest, and development of molecular markers for
      genotyping and mapping.

PMID- 29213354
TI  - Chemical Composition and Pharmacological Effects of Geopropolis Produced by
      Melipona quadrifasciata anthidioides.
AB  - Stingless bees produce geopropolis, which is popularly described for its
      medicinal properties, but for which few scientific studies have demonstrated
      pharmacological effects. The objective of this study was to investigate the
      chemical composition of the geopropolis of Melipona quadrifasciata anthidioides
      and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and
      antimicrobial activities. The composition of the hydroethanolic extract of
      geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside
      derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant
      action via the direct capture of free radicals and by inhibiting the levels of
      oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative
      stress. HEG also reduced the frequency of gene conversion and the number of
      mutant colonies of S. cerevisiae. The anti-inflammatory action of HEG was
      demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG
      induced cell death in all evaluated gram-positive bacteria, gram-negative
      bacteria, and yeasts, including clinical isolates with antimicrobial drug
      resistance. Collectively, these results demonstrate the potential of M. q.
      anthidioides geopropolis for the prevention and treatment of various diseases
      related to oxidative stress, mutagenesis, inflammatory processes, and microbial
      infections.

PMID- 29213356
TI  - High-quality draft genome sequence of Aquidulcibacter paucihalophilus TH1-2T
      isolated from cyanobacterial aggregates in a eutrophic lake.
AB  - Aquidulcibacter paucihalophilus TH1-2T is a member of the family Caulobacteraceae
      within Alphaproteobacteria isolated from cyanobacterial aggregates in a eutrophic
      lake. The draft genome comprises 3,711,627 bp and 3489 predicted protein-coding
      genes. The genome of strain TH1-2T has 270 genes encoding peptidases. And metallo
      and serine peptidases were found most frequently. A high number of genes encoding
      carbohydrate active enzymes (141 CAZymes) also present in strain TH1-2T genome.
      Among CAZymes, 47 glycoside hydrolase families, 37 glycosyl transferase families,
      38 carbohydrate esterases families, nine auxiliary activities families, seven
      carbohydrate-binding modules families, and three polysaccharide lyases families
      were identified. Accordingly, strain TH1-2T has a high number of transporters
      (91), the dominated ones are ATP-binding cassette transporters (61) and TonB
      dependent transporters (28). Major TBDTs are Group I, which consisted of
      transporters for various types of dissolved organic matter. These genome features
      indicate adaption to cyanobacterial aggregates microenvironments.

PMID- 29213357
TI  - Genome overview of eight Candida boidinii strains isolated from human activities
      and wild environments.

PMID- 29213358
TI  - Intratumoral treatment with radioactive beta-emitting microparticles: a
      systematic review.
AB  - Purpose: The purpose of this study was to review the role of radioactive
      microparticles (1-100 MUm) for the treatment of solid tumors and provide a
      comprehensive overview of the feasibility, safety, and efficacy. Methods: A
      systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library
      (January 2017) by combining synonyms for the determinants "tumor," "injection,"
      and "radionuclide." Data on injection technique, toxicity, tumor response, and
      survival were collected. Results: The search yielded 7271 studies, and 37 were
      included for analysis. Twelve studies were performed in human patients and 25
      animal studies. The studies were heterogeneous in patient population, tumors,
      follow-up time, and treatment characteristics. The direct intratumoral injection
      of radioactive microparticles resulted in a response rate of 71% in a variety of
      tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were
      reported. Conclusion: The large variety of particles, techniques, and treated
      tumors in the studies provided an important insight into issues concerning
      efficacy, safety, particle and isotope choice, and other concepts for future
      research. Animal studies showed efficacy and a dose response. Most studies in
      humans concluded that intratumoral treatment with radioactive beta-emitting
      microparticles is relatively safe and effective. Conflicting evidence about
      safety and efficacy might be explained by the considerable variation in the
      treatment characteristics. Larger particles had a better retention which resulted
      in higher anti-tumor effect. Leakage seems to follow the path of least resistance
      depending on anatomical structures. Subsequently, a grid-like injection procedure
      with small volume depots is advised over a single large infusion. Controlled
      image-guided treatment is necessary because inadequate local delivery and
      inhomogeneous dose distribution result in reduced treatment efficacy and in
      potential complications.

PMID- 29213360
TI  - Rationale for launching a new journa.
AB  - Vascular cognitive impairment/vascular dementia have been the subject of a large
      number of studies, due to their high prevalence and broad preventive and
      compensatory therapeutic potential. The knowledge of the cerebral anatomy
      correlated to the vascular territories of irrigation enables understanding of
      clinical manifestations, as well as classification into the several types of
      syndromic presentations. The central cholinergic system exercises important
      neuromodulatory functions on cerebral circuits related to cognitive and
      behavioral integration, as well as on vasomotor control related to cerebral blood
      flow adjustments. The acquisition of data on the anatomy of the cholinergic
      pathways, including the localization of the nuclei of the basal prosencephalon
      and the routes of their projections, established an important milestone. The
      knowledge of the vascular distribution and of the trajectories of the cholinergic
      pathways allows identification of the strategic points where a vascular lesion
      can cause interruption. The ensuing denervation leads to cholinergic hypofunction
      in the involved territories. This information proves important to better evaluate
      the sites of vascular lesions, emphasizing their strategic localizations in
      relation to the cholinergic pathways, and offering more robust foundations for
      treatment aiming at enhancing cholinergic activity.

PMID- 29213359
TI  - Influence of radiation treatment technique on outcome and toxicity in anal
      cancer.
AB  - Objective: Intensity-modulated radiation therapy (IMRT) has largely supplanted
      three-dimensional conformal radiation (3D-CRT) for definitive anal cancer
      treatment due to decreased toxicity and potentially improved outcomes. Convincing
      data demonstrating its advantages, however, remain limited. We compared outcomes
      and toxicity with concurrent chemotherapy and IMRT vs 3D-CRT for anal cancer.
      Methods: We performed a single-institution retrospective review of patients
      treated with IMRT or 3D-CRT as part of definitive mitomycin-C/5-fluorouricil
      based chemoradiation for anal cancer from January 2003 to December 2012. Results:
      One hundred sixty-five patients were included, with 61 and 104 receiving IMRT and
      3D-CRT, respectively. Overall, 92.7% had squamous cell carcinoma. The mean
      initial pelvic dose was 48.3 and 44 Gy for IMRT and 3D-CRT, respectively.
      Complete response, partial response, and disease progression rates were similar
      (IMRT 83.6, 8.2, 8.2%; 3D-CRT 85.6, 6.7, 7.7%; p = 0.608, p = 0.728, p = 0.729).
      There was no significant difference in overall survival (p = 0.971), event-free
      survival (p = 0.900), or local or distant recurrence rates (p = 0.118, p =
      0.373). IMRT caused significantly less acute grade 1-2 incontinence (p = 0.035),
      grade 3-4 pain (p = 0.033), and fatigue (p = 0.030). IMRT patients had
      significantly fewer chronic post-treatment toxicities (p = 0.008), outperforming
      3D-CRT in six of eight toxicities reviewed. Though total treatment length was
      comparable (43.6 and 44.5 days), IMRT recipients had fewer (27.9 vs 41.3% of
      patients, p = 0.89), shorter treatment breaks (mean 2.9 vs 4.1 days, p = 0.229).
      Conclusion: This report represents the largest series directly comparing
      concurrent chemotherapy with IMRT vs 3D-CRT for definitive treatment of anal
      cancer. IMRT significantly reduced acute and post-treatment toxicities and
      allowed for safe and effective pelvic dose escalation.

PMID- 29213361
TI  - Vascular dementia and the cholinergic pathways.
AB  - Vascular cognitive impairment/vascular dementia have been the subject of a large
      number of studies, due to their high prevalence and broad preventive and
      compensatory therapeutic potential. The knowledge of the cerebral anatomy
      correlated to the vascular territories of irrigation enables understanding of
      clinical manifestations, as well as classification into the several types of
      syndromic presentations. The central cholinergic system exercises important
      neuromodulatory functions on cerebral circuits related to cognitive and
      behavioral integration, as well as on vasomotor control related to cerebral blood
      flow adjustments. The acquisition of data on the anatomy of the cholinergic
      pathways, including the localization of the nuclei of the basal prosencephalon
      and the routes of their projections, established an important milestone. The
      knowledge of the vascular distribution and of the trajectories of the cholinergic
      pathways allows identification of the strategic points where a vascular lesion
      can cause interruption. The ensuing denervation leads to cholinergic hypofunction
      in the involved territories. This information proves important to better evaluate
      the sites of vascular lesions, emphasizing their strategic localizations in
      relation to the cholinergic pathways, and offering more robust foundations for
      treatment aiming at enhancing cholinergic activity.

PMID- 29213362
TI  - 'To do or not to do'? The neurobiology of decision-making in daily life: I.
      Getting the basics.
AB  - The constant conflict between decisions leading to immediate pleasurable
      consequences versus behaviors aiming at long-term social advantages is reviewed
      here in the framework of the evolutionary systems regulating behavior. The
      inescapable temporal perspective in decision-making in everyday life is
      highlighted and integrated with the role of the executive functions in the
      modulation of subcortical systems. In particular, the representations of the 'non
      existent' future in the prefrontal cortical regions and how these representations
      can bridge theory and practice in everyday life are addressed. Relevant
      discussions regarding the battle between emotions and reasons in the
      determination of more complex decisions in the realm of neuroeconomics and in
      moral issues have been reserved for a second essay.

PMID- 29213363
TI  - Cognitive and functional dementia assessment tools: review of Brazilian
      literature.
AB  - : The diagnosis of dementia is based on cognitive and functional evaluation. One
      of the difficulties in ascertaining the number of people with dementia in
      developing countries is the population's lack of formal education. Independent
      effects of age, sex and education have been identified on scores for most but not
      all cognitive tests. Objectives: Identify the most-used cognitive and functional
      assessment tools in Brazil, related to dementia diagnosis and treatment outcome;
      and identify adaptations or normative data, when available. Methods: Data were
      generated from PubMed, LILACS and Portal Periodicos CAPES (thesis database)
      databases using the search terms 'dementia' and 'Alzheimer'. Data collection
      criteria were a. Articles with abstract; b. Brazilian abstracts, related to adult
      Brazilian population; c. Clear mention of assessment tool in the abstract text. A
      total of 108 abstracts were selected for the main analysis: a. to identify the
      instruments used b. to determine how many of the selected abstracts mentioned
      each tool and c. to search in the mentioned databases for respective test
      adaptations or normative data. Results: Some 52 different assessment tools, 41
      cognitive instruments and 11 functional instruments were identified. The most
      cited assessment tests were the Mini Mental State Examination (64 abstracts) and
      Pfeffer Functional Activities Questionnaire (4 abstracts). Discussion: Many of
      the instruments used only have the description of the translation process into
      Portuguese, along with some suggestions of validation or normative data. Few of
      these followed the recommended procedures of validation, replication,
      normalization or transcultural adaptation.

PMID- 29213364
TI  - Education did not interact with major depression on performance of memory tests
      in acute southern Brazilian in patients.
AB  - : The relationship of cognitive function to depression in older adults has become
      a topic of extensive clinical interest and research. Objective: To analyze
      association between cognitive/memory performance,Major Depression, and education
      in 206 inpatients from the Psychiatry and Internal Medicine Departments. Methods:
      Patients were evaluated by the Mini Mental State Examination, a battery of memory
      tests, and the Montgomery-Asberg Depression Rating Scale. Depression patients
      comprised 45 severe and 42 mild/moderate, according to the Montgomery-Asberg
      scale. The effect of psychoactive drugs was recorded (30% drug-free). Education
      was measured in years. Cognitive/memory tests assessed five domains: general
      mental functioning, attention, sustained attention/working memory, learning
      memory (verbal), and remote memory. An index for memory impairment was created
      (positivity: 50% of tests below cutoff). Results: The chief effect on worse
      performance was Major Depression for the domains (age and education adjusted) of
      attention, learning, remote memory, and general functioning. For the domain
      "sustained attention and working memory", only severely depressed patients
      differed from the medical controls (p=.008). Education showed an independent
      effect on test performances. No interaction between depression and educational
      status was observed.We also observed an independent effect of psychoactive drugs
      on some cognitive/memory domains. Logistic Regression showed Major Depression as
      the main risk for cognitive impairment. Conclusions: These data demonstrated
      association of Major Depression with impaired cognitive performance independent
      of educational attainment or psychiatric medications.

PMID- 29213365
TI  - Brief cognitive battery in the diagnosis of mild Alzheimer's disease in subjects
      with medium and high levels of education.
AB  - : There has been an increasing trend to utilize short cognitive batteries for the
      diagnosis of dementia. Most of these batteries have been designed in countries
      with high standards of education and are less suitable for populations with low
      levels of education.We developed a battery that has been previously shown to be
      highly accurate in the diagnosis of dementia in individuals with low levels of
      education. The accuracy of this battery for patients with higher levels of
      education is unknown. Objectives: To evaluate the accuracy of a brief cognitive
      battery in the diagnosis of Alzheimer's disease (AD) in subjects with medium and
      high levels of schooling, and to develop a mathematical model that includes the
      most discriminative tests. Methods: Seventy-three mildly demented patients with
      probable AD and 94 control subjects were evaluated. Sixty patients and 60
      controls were randomly selected to generate a mathematical model including the
      most discriminative tests of the battery using logistic regression. The model was
      back-tested for the remaining sample of patients and controls. Results: Delayed
      recall, learning and category fluency tests were included in a mathematical model
      that obtained an area of 0.917 in the ROC curve in the back-testing. Inter-rater
      reliabilities of these tests were high (kappa>0.8). Conclusions: This model
      showed a high accuracy for the diagnosis of mild AD in patients with medium and
      high educational levels. Future studies with more heterogeneously educated
      individuals are necessary to investigate whether the educational level (number of
      years at school) should also be included in the model.

PMID- 29213366
TI  - Analysis of brief language tests in the detection of cognitive decline and
      dementia.
AB  - : Lexical access difficulties are frequent in normal aging and initial stages of
      dementia.Verbal fluency tests are valuable to detect cognitive decline,
      evidencing lexico-semantic and executive dysfunction. Objectives: To establish
      which language tests can contribute in detecting dementia and to verify schooling
      influence on subject performance. Method: 74 subjects: 33 controls, 17 Clinical
      Dementia Rating (CDR) 0.5 and 24 (Brief Cognitive Battery - BCB e Boston Naming
      Test - BNT) 1 were compared in tests of semantic verbal fluency (animal and
      fruit), picture naming (BCB and BNT) and the language items of Mini Mental State
      Examination (MMSE). Results: There were significant differences between the
      control group and both CDR 0.5 and CDR 1 in all tests. Cut-off scores were: 11
      and 10 for animal fluency, 8 for fruit fluency (in both), 8 and 9 for BCB naming.
      The CDR 0.5 group performed better than the CDR 1 group only in animal fluency.
      Stepwise multiple regression revealed fruit fluency, animal fluency and BCB
      naming as the best discriminators between patients and controls (specificity:
      93.8%; sensitivity: 91.3%). In controls, comparison between illiterates and
      literates evidenced schooling influence in all tests, except for fruit fluency
      and BCB naming. In patients with dementia, only fruit fluency was uninfluenced by
      schooling. Conclusion: The combination of verbal fluency tests in two semantic
      categories along with a simple picture naming test is highly sensitive in
      detecting cognitive decline. Comparison between literate and illiterate subjects
      shows a lesser degree of influence of schooling on the selected tests, thus
      improving discrimination between low performance and incipient cognitive decline.

PMID- 29213367
TI  - The influence of schooling on cognitive screening test in the elderly.
AB  - Introduction: Tests for screening cognitive functions are gaining importance with
      the increasing incidence and prevalence of demential syndromes. For our elderly
      population, the challenge is to develop neuropsychological tests independent from
      the influence of educational level. Objective: To compare the influence of
      education on the elderly with or without cognitive decline, on the Brief
      Cognitive Screening Battery (BCSB). Methods: We studied 176 elderly people: 60
      with cognitive decline (aged 73.6+/-9.3 years and with 5.7+/-0.7 years of
      education) and 116 without cognitive impairments (aged 73.4+/-0.6 years and with
      5.6+/-0.5 years of education). The BCSB was applied in all subjects. The data
      were submitted to descriptive statistics and analyzed by Independent Student test
      with 95% confidence intervals. Results: The data showed that the BCSB is an
      appropriate battery for identifying cognitive status in normal elderly
      individuals, as well as cognitive decline in our elderly sample. The BCSB items
      were not significantly influenced by schooling years, making this test favorable
      for different groups characterized by illiterate individuals, as well as by those
      with low or high levels of formal education. Conclusion: The BCSB proved to be a
      useful cognitive screening test for old people with or without cognitive decline
      independent of their educational level.

PMID- 29213368
TI  - How many items from a word list can Alzheimer's disease patients and normal
      controls recall? Do they recall in a similar way?
AB  - : The serial position effect occurs when individuals are asked to recall a list
      of information that exceeds normal attention span. Alzheimer's disease (AD)
      patients show lower scores on word span recall tests when compared to healthy
      aging subjects, younger individuals or depressed patients. Objective: To evaluate
      the immediate free recall and the serial position effect of a 10-word list,
      emotionally neutral in tone, in Alzheimer's disease (AD) patients and two age
      groups of healthy controls. Methods: The free word recall test was applied in a
      sample of 44 mild AD outpatients and 168 >50 year and 173 =50 year-old healthy
      controls. The span of recalled words and order of recollection of each item was
      recorded. Scores for serial position effect were analyzed.MMSE scores were
      recorded for all participants. Descriptive statistics and the ANOVA with Tukey
      test were performed. Results: The controls scored significantly better than AD
      patients on the MMSE and word span (p=0.0001). Older controls word span mean +/
      SD was 5.65+/-1.75, younger controls was 5.99+/-1.27, and AD patients was 2.86+/
      1.42. The best recalled item in all groups was the first item of the list.
      Primacy was observed across the three groups, although AD patients presented
      lower scores. Recency was diminished among AD patients compared to control
      groups. Conclusions: Primacy effect was observed in AD patients as well as in
      both normal control groups. Recency effect was presented by the normal control
      groups but was extremely poor among AD patients. The first item was universally
      best retrieved.

PMID- 29213369
TI  - Brazilian version of the Frontal Assessment Battery (FAB): Preliminary data on
      administration to healthy elderly.
AB  - : The Frontal Assessment Battery (FAB) has been proposed as a diagnostic tool for
      patients with frontal lobe syndrome. Objectives: To present the Brazilian version
      of the FAB and to show preliminary data on the performance of healthy elderly in
      the battery, correlating with age, education and scores in the Mini- Mental State
      Examination (MMSE). Methods: Forty-eight healthy elderly individuals (34
      female/14 male) were evaluated, aged 69.3+/-6.1 years and with educational
      level=8.0+/-5.6 years. The subjects were submitted to the MMSE, the Cornell
      depression scale and the FAB, in which scores were determined for each item and
      for the total scale. All individuals had to attain above education adjusted cut
      off scores in the MMSE and =7 points on the Cornell depression scale.
      Correlations were calculated between FAB total scores and age, educational level
      and MMSE scores, as well as between FAB items and education. Results: The mean
      score +/-SD in the FAB was 13.0+/-2.3(7 to 18). Total FAB scores correlated
      significantly with education (r=0.37; p=0.01) and MMSE scores (r=0.46; p=0.001).
      No correlation emerged between FAB scores and age. The mean score +/-SD of the
      MMSE was 27.4 +/- 1.8. Considering the six FAB items separately, two of them
      (similarities and conflicting instructions) correlated significantly with
      educational. Conclusions: In this group of healthy elderly, the Brazilian version
      of the FAB proved to be influenced by education, but not age.

PMID- 29213370
TI  - Iowa gambling task: Administration effects in older adults.
AB  - : The Iowa Gambling Task (IGT) assesses decision-making. Objective: The objective
      of the present study was to investigate whether specific changes in administering
      the IGT can affect performance of older adults completing the task. Method: Three
      versions of the IGT were compared regarding the feedback on the amount of money
      won or lost over the course of the test. The first version (I) consisted of a
      replication of the original version (Bechara et al., 1994), which utilizes a
      computerized visual aid (green bar) that increases or decreases according to the
      gains or the losses. The second version (II), however, involved a non
      computerized visual aid (cards) and, in the third version (III) the task did not
      include any visual aid at all. Ninety-seven older adults, divided into three
      groups, participated in this study. Group I received computerized cues (n=40),
      group II, non-computerized cues (n=17) and III was submitted to a version without
      any cues (n=40). Results: The participants without any cues achieved only a
      borderline performance, whereas for those with non-computerized cues, twice the
      number of participants showed attraction to risk in relation to those with
      aversion. The participants of the computerized version were homogeneously spread
      across the three performance levels (impaired, borderline and unimpaired).
      Conclusions: Aspects of the complexity of the decision process as well as of the
      task used are proposed as possible theoretical explanations for the performance
      variation exhibited.

PMID- 29213371
TI  - Awareness of disease in dementia: Development of a multidimensional rating scale.
AB  - Objective: To describe the development of the Assessment Scale of Psychosocial
      Impact of the Diagnosis of Dementia (ASPIDD), a multidimensional scale to
      evaluate awareness of disease in dementia. Method: The development of this scale
      was conducted in four steps. In step one, questions were drawn up after a review
      of the literature. The second step involved the suggestions offered by a
      neurologist regarding the skills considered important for the scale. The third
      step involved the re-writing and review of the domains and questions in the scale
      followed by a semantic evaluation performed by two independent psychiatrists.
      Step four consisted of the preliminary study aimed at evaluating the
      applicability of the ASPIDD. Results: In the semantic evaluation only minor
      changes were proposed. The preliminary sample had 52 patients, comprising 23 CDR
      1 (male=9; female=14) and 29 CDR2 (male=13; female=16).Mean age of patients was
      69.7+/-5.51(CDR1) and 73.6+/-9.4 (CDR2), and age at onset was 66.4+/-5.7 years
      (CDR1) and 68.3+/-9.3 year (CDR2).Mean schooling was 9.0+/-4.3 years (CDR1) and
      8.8+/-4.4 years (CDR2). Mean MMSE was 21.0+/-3.3(CDR1) and 17.6+/-3.5(CDR2).Mean
      Cornell was 4.8+/-2.3(CDR1) and 4.2+/-1.9 (CDR2). The patient and caregiver dyads
      were aware of problems, mainly of those related to social, family and affective
      relations. The higher rates of discrepant responses were found on the awareness
      of cognitive deficits and changes in ADL. Conclusion: The ASPIDD is a
      multidimensional instrument to assess awareness of disease among AD patients.

PMID- 29213372
TI  - Anosognosia in Alzheimer's disease: A neuropsychological approach.
AB  - : Anosognosia is often found in Alzheimer's disease (AD), but its relationship
      with cognitivebehavioral changes is not well established. Objective: To verify if
      anosognosia is related to cognitive-behavioral disturbances, and to regional
      brain dysfunction as evaluated by neuroimaging. Methods: We included AD patients
      with Mini-Mental State Examination (MMSE) scores of 12 through 24, and Clinical
      Dementia Rating (CDR) scores of 1 or 2. Dementia diagnosis was based on DSM-IV
      and NINCDS-ADRDA criteria.We used Self-Consciousness Questionnaire (SCQ) and
      Denial of Illness Scale (DIS), and following neuropsychological counterproofs:
      WAIS-R digit span, Rey auditory verbal learning, verbal fluency test (category:
      animals), Cummings' neuropsychiatric inventory (NPI) and Cornell scale for
      depression in dementia (CSDD). Results: We studied 21 patients (12 men, 9 women)
      with AD (14 mild, 7 moderate), age 72.4+/-8.5 years, education 4.9+/- 4.2 years,
      and MMSE score 18.2+/-5. SCQ and DIS did not correlate to age, education, or
      regional cerebral perfusion defects, but they tended to correlate to disease
      duration (and only SCQ also to MMSE). SCQ and DIS were correlated neither to
      CSDD, NPI, CDR, nor to any neuropsychological test. Significant correlations were
      found between SCQ and DIS, as well as between SCQ domain of "moral judgment" and
      MMSE. Conclusion: SCQ and DIS were not correlated to age, education, disease
      duration, cognitive-behavioral measures, dementia severity, or regional cerebral
      perfusion defects, but were correlated to each other, suggesting SCQ and DIS
      evaluate similar mental functions.

PMID- 29213373
TI  - Diagnosis and rehabilitation attempt of a patient with acquired dyslexia.
AB  - : Although dyslexia is a common consequence of brain damage there are few studies
      about therehabilitation of this disorder. Cognitive Neuropsychology models of
      reading have been used to describe severalsyndromes of acquired dyslexia.
      Phonological dyslexia is a reading disorder characterized by a
      dysfunctionalgrapheme-to-phoneme conversion procedure, which affects the ability
      to read low frequency words and nonwords. Lexical reading is preserved and
      patients can read frequent words (regular and irregular). Objective: Verify the
      application of the cognitive model in the characterization of the reading
      disorder of a patient with acquired dyslexia and in the devising and
      implementation of a rehabilitation plan. Methods: This study presents OCS, a 57
      year-old patient who suffered from acquired phonological dyslexia after a left
      temporo-parietooccipital ischemic stroke. A rehabilitation program based on the
      principles of Cognitive Neuropsychology was devised non-words and low frequency
      words with controlled lengths were used and the patient was stimulated to read
      them aloud in a 22-session treatment. Results: The post-test evaluation showed
      quantitative and qualitative improvements Significant improvements were verified
      in the total number of correct responses including self-correction attempts
      (p<0.01) and in the reading of trisyllabic and polysyllabic non-words of simple
      syllabic structure (p=0.0007 and p=0.02 respectively). Conclusions: The use of
      the cognitive model to devise a rehabilitation program was successful and we
      observed significant improvement of reading skills in a short period of
      treatment. The achievements over this period provided the patient with functional
      reading performance.

PMID- 29213374
TI  - Reports by caregivers of behavioral and psychological symptoms of dementia.
AB  - : Behavioral and Psychological Symptoms of Dementia (BPSD) are relevant since
      they are frequent and cause distress to caregivers. However, they may not be
      reported by physicians due to the priority usually attributed to cognitive
      symptoms. Objectives: To verify whether BPSD is being systematically investigated
      by physicians even in specialized settings and whether their records on medical
      files are accurate. Methods: Assessment of records on medical files of BPSD
      reported by caregivers to 182 patients (57.1% men, mean age 67.6+/-13.5 years)
      assisted in a tertiary-care behavioral neurology outpatient clinic (BNOC) who
      also had appointments in other clinics of the same hospital. Alzheimer's disease
      (37.9%) and vascular disease (19.2%) were the most frequent causes of dementia.
      Results: Report/appointment ratios were 0.58 in BNOC, 0.43 in other neurological,
      0.93 in psychiatric and 0.20 in non-neurological, non-psychiatric clinics. BPSD
      most frequently recorded in BNOC were insomnia, aggressiveness,
      agitation/hyperactivity, visual hallucinations, apathy, inadequate behavior and
      ease of crying. Sorted by psychiatrists, categories associated to more BPSD were
      affect/mood, thought and personality/behavior. affect/mood and sensoperception
      symptoms were the most frequently reported. Sorted according to Neuropsychiatric
      Inventory (NPI), categories associated to more BPSD were depression/dysphoria,
      delusion and apathy/indifference. depression/dysphoria and agitation/ aggression
      symptoms were the most frequently reported. Conclusions: BPSD reported by
      caregivers were very diverse and were not systematically investigated by
      physicians. Notes in medical files often contained non-technical terms.

PMID- 29213375
TI  - Visual agnosia and prosopagnosia secondary to melanoma metastases: case report.
AB  - The association of visual agnosia and prosopagnosia with cerebral metastasis is
      very rare. The presence of symmetric and bilateral cerebral metastases of
      melanoma is also uncommon.We report the case of a 34 year-old man who was
      admitted to hospital with seizures and a three-month history of headache, with
      blurred vision during the past month. A previous history of melanoma resection
      was obtained. CT of the skull showed bilateral heterogeneous hypodense lesions in
      the occipito-temporal regions, with a ring pattern of contrast enhancement.
      Surgical resection of both metastatic lesions was performed after which the
      patient developed visual agnosia and prosopagnosia. On follow-up, he showed
      partial recovery of visual agnosia, while prosopagnosia was still evident. The
      relevance of this case is the rare presentation of metastatic malignant melanoma
      affecting homologous occipito-temporal areas associated with prosopagnosia and
      associative visual agnosia.

PMID- 29213376
TI  - Basic and clinical research, and the review of original papers.

PMID- 29213377
TI  - Targeting the gastrin-releasing peptide receptor pathway to treat cognitive
      dysfunctionassociated with Alzheimer's Disease.
AB  - Increasing evidence indicates that bombesin (BB)-like peptides (BLPs), such as
      the gastrin-releasing peptide (GRP) and its receptor (GRPR), might play a role in
      neurological and psychiatric disorders. The present study reviews findings from
      animal and human studies suggesting that the GRPR should be considered a target
      for the treatment of cognitive dysfunction in patients with Alzheimer's disease
      (AD). Abnormalities in GRPR-triggered signaling have been described in both
      fibroblasts from patients with AD, and in transgenic mouse models of AD.
      Pharmacological and genetic preclinical studies have indicated that BLPs and the
      GRPR are importantly involved in regulating cognitive function. Moreover, drugs
      acting at the GRPR have been shown to enhance memory and ameliorate cognitive
      dysfunction in experimental models of amnesia associated with AD. Taken together,
      these findings support the view that the GRPR is a novel therapeutic target for
      the treatment of memory deficits associated with AD.

PMID- 29213378
TI  - The dementias of schizophrenia.
AB  - Cases of "adolescent insanity" were known to Kraepelin's forerunners and lay at
      the core of his concept of dementia praecox. In the post-neuroleptic era it
      became clear that dementia may also occur in schizophrenia as a fully reversible
      state depending on psychopathological status. In the present review we discuss
      the validity of applying the concept of dementia to schizophrenia. We concur with
      the view that schizophrenia may lead to a true dementia both (i) as a fixed end
      stage consequence of the disease process itself, or (ii) as a drug-responsive
      reversible state. There is an urgent need to examine the patterns of dementia in
      other common neuropsychiatric disorders, employing current methods of
      neurobehavioral investigation.

PMID- 29213379
TI  - What matters in white matter dementia?
AB  - Dementia studies has primarily focused on disorders of the cerebral cortex and
      subcortical gray matter, what originated the concepts of cortical and subcortical
      dementias respectively. Dementia related mainly with cerebral white matter have
      received less attention. We present five different cases, each one illustrative
      of a dementia subtype that could be assigned under the category of 'white matter
      dementia': CADASIL, progressive subcortical gliosis, progressive multifocal
      leucoencephalopathy, normopressure hydrocephalus and brain injury. Besides that,
      recent clinical and scientific literature on white matter dementia was reviewed.
      The composition of exuberant psychiatric symptoms and personality changes (mainly
      apathy, but also desinhibition) with neurological signs (pyramidal alone or
      associated with extrapyramidal signs, ataxia and urinary incontinence) and with
      specific cognitive impairment (mentioned above), should rise strongly the
      possibility of a white-matter dementia, instead of a cortical or subcortical form
      of dementia.

PMID- 29213380
TI  - Computer-assisted 3D reconstruction of the human basal forebrain complex.
AB  - : The basal forebrain complex (BFC) is a small but intricate structure. Its
      organization and function is hard to investigate using conventional methods,
      especially in humans. By combining new methods of research we present a
      comprehensive overview of this complex, in order to better understand its
      function in normal and diseased brains. Methods: The right and left BFC of a 29
      year-old male were reconstructed from gallcocyanin (Nissl) stained 440 um-thick
      serial horizontal sections by using advanced computer-assisted 3D reconstruction
      software. Results: The reconstructed components in the present case include Ch2,
      Ch3, Ch4am-al, Ch4i, Ch4p, juxtacommissural, Ayala's medial (subpallidal) and
      lateral (periputaminal) subnuclei. These components are arranged in an arch-like
      course mainly beneath the anterior commissure. The bilateral volume of all
      subnuclei was 99.06 mm3, the left side accounting for 48.05 mm3. Some of the
      subnuclei exhibited volume asymmetry indices varying from 28.3 to 12.9%.The
      volume of Ayalas' lateral or periputaminal nucleus was 9.7% higher on the right,
      than on the left side. Conclusions: Our methodological approach promises to be
      highly efficient and reproducible in studying morphofunctional correlations in
      complex cognitive features.

PMID- 29213381
TI  - Working memory: Differences between young adults and the aged in listening tasks.
AB  - : Working memory is a system with a limited capacity which enables the temporary
      storage and manipulation of the information necessary for complex cognitive
      tasks. Numerous studies have suggested that performance in these tasks is related
      to age where older adults have a lesser performance than the young. Objective: To
      analyze the processing functions of working memory in a listening task. Method:
      59 educated participants aged between 19 and 76 years having no memory complaints
      were divided into two groups (young and aged adults). The test administered was
      the adapted Listening Span, in which the subject listens to a sentence, judging
      whether it is true or false and, concomitantly, stores the last word of each
      sentence for later evocation. Results: In the judgment task, performance of both
      groups approached to a similar average. Results of sentence recall demonstrated
      that with the increase in number of sentences at each level, performance of both
      groups declined. In the blocks of sentences 1 and 2 at level 1, all participants
      performed similarly. In the block of sentences 3, at level 1, there was a
      difference between the young and the aged. From this level onward (retention of 3
      to 5 items), the aged and the young differed significantly. Conclusions: An
      increase in the number of sentences diminished participants' performance of
      temporary storage in the recall tasks, while not interfering in the processing of
      sentences during judgment. The difference between the young and the aged became
      more accentuated as item retention demands increased.

PMID- 29213382
TI  - Behavioural assessment of the dysexecutive syndrome (BADS) in healthy elders and
      Alzheimer's disease patients: preliminary study.
AB  - : Although the main initial deficit is considered to be in the memory domain, an
      early impairment of executive functions is also found in AD where these deficits
      are correlated to functional impairment. Ecological tests are more indicated to
      evaluate executive impairment, and are better able to assist in treating AD
      patients than more commonly used tests. Objectives: The aim of this preliminary
      study is to verify the performance in executive functions using the Behavioural
      Assessment of the Dysexecutive Syndrome (BADS) in elder controls and mild AD
      patients, and to analyze its applicability in our environment. Methods: The BADS
      was performed by 17 healthy elders and 17 early AD patients matched for age,
      schooling and gender. Results: There were significant differences among controls
      and AD patients on MMSE scores, and in measures of executive functions, memory,
      and motor speed. Some sub items of BADS (rule shift cards, modified six elements,
      total score, standard, standard by age and overall classification by age) were
      also different between groups. Differences were also significant on the
      Dysexecutive Questionnaire (DEX) of BADS self-ratings and other-ratings.
      Conclusion: BADS was efficacious in detecting executive deficits in this sample,
      as confirmed by other executive functions tests applied.

PMID- 29213383
TI  - Category verbal fluency performance may be impaired in amnestic mild cognitive
      impairment.
AB  - : To study category verbal fluency (VF) for animals in patients with amnestic
      mild cognitive impairment (aMCI), mild Alzheimer disease (AD) and normal
      controls. Method: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were
      included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, while
      aMCI was based on the criteria of the International Working Group on Mild
      Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects
      underwent testing of category VF for animals, lexical semantic function (Boston
      Naming-BNT, CAMCOG Similarities item), WAIS-R forward and backward digit span,
      Rey Auditory Verbal Learning (RAVLT), Mini-Mental Status Examination (MMSE), and
      other task relevant functions such as visual perception, attention, and mood
      state (with Cornell Scale for Depression in Dementia). Data analysis used ANOVA
      and a post-hoc Tukey test for intergroup comparisons, and Pearson's coefficient
      for correlations of memory and FV tests with other task relevant functions
      (statistical significance level was p<0.05). Results: aMCI patients had lower
      performance than controls on category VF for animals and on the backward digit
      span subtest of WAIS-R but higher scores compared with mild AD patients. Mild AD
      patients scored significantly worse than aMCI and controls across all tests.
      Conclusion: aMCI patients may have poor performance in some non-memory tests,
      specifically category VF for animals in our study, where this could be
      attributable to the influence of working memory.

PMID- 29213384
TI  - Knowledge of semantic categories in normal aged: Influence of education.
AB  - : Semantic memory seems to resist the effects of time, remaining stable even in
      more advanced ages. Objective: To verify the effect of schooling level on
      semantic knowledge (non-living items) in normal aged. Method: 48 aged individuals
      were divided into three groups (based on schooling) and evaluated. Three tests
      were applied: verbal fluency, naming and figure classification. Results: We
      verified that the group with greater schooling (>8 years) differed to the
      illiterate and low schooling groups in most of the tasks, evoking more items in
      verbal fluency, correctly naming more items and presenting a greater number of
      "formal categories". Discussion: In the verbal fluency test, this difference
      could be explained by the types of strategies used by the individuals to recall
      words. In relation to the naming test, the effect could be attributed to
      limitation in the vocabulary and cognitive processing skills needed to search for
      semantic attributes of the figures. In categorization, this type of
      classification is dependent on scholastic learning. Conclusion: We concluded that
      both illiterate elderly and those having a low schooling level, presented poorer
      performance in semantic memory tests compared to the aged with a higher level of
      schooling. The similar behavior evidenced between illiterate and low schooling
      groups is intriguing. It remains unclear whether the low schooling group behaved
      like the illiterates or vice-a-versa. This unanswered question remains the
      subject of future studies.

PMID- 29213385
TI  - Pre- and post-operative Wisconsin card sorting test performance in patients with
      temporal lobe epilepsy due to hippocampal sclerosis.
AB  - : Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have
      a distinct neuropsychological profile, but there is still debate on whether
      executive dysfunction is part of this profile and also whether temporal lobe
      surgery can modify this dysfunction. Objective: To study the presence and
      reversibility of executive dysfunction in patients with unilateral TLE/HS.
      Methods: Twenty-five patients with refractory seizures due to TLE/HS underwent
      presurgical evaluation which included the application of the Wiconsin Card
      Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months
      after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects
      matched for age and education also performed the WCST. Results: Sixteen of the 25
      patients (64%) completed fewer than four categories in the WCST whereas only 4 of
      the 22 controls (18%) did not complete at least four categories (p<0.005). In
      addition, the performance of the patients involved significantly more
      perseverative responses and errors compared to controls. The patient group
      demonstrated significant post-operative improvement in many measures of the WCST
      following SAH. Conclusions: These findings support the presence of executive
      dysfunction in patients with TLE/HS and suggest that such dysfunction can be
      partially reversed by selective resection of epileptogenic mesial temporal
      structures.

PMID- 29213386
TI  - Typical performance of elderlypatients with Alzheimer disease on the Wisconsin
      Card Sorting Test (WCST).
AB  - : The Wisconsin Card Sorting Test (WCST) is a neuropsychological assessment tool
      designed to assess executive functions, frequently used in cases of cognitive
      disorders. However, Brazilian neuroscientific settings lack standardization
      studies of psychological assessment instruments, especially in the
      neuropsychological area. Thus, the assessment of clinical groups including
      dementias and particularly Alzheimer's disease (AD) patients, may be compromised
      by the lack of analytical references. Objective: To characterize the performance
      of elderly patients with Alzheimer's disease on the WCST, aiming at establishing
      preliminary evaluative norms. Method: Thirty-six elderly patients (mean age of
      75.8 years) with mild AD from a teaching hospital were assessed using the printed
      form of the WCST. Results: The elderly patients with AD had impaired performance
      on the various WCST technical indicators, highlighting cognitive deficit with
      traces of stereotyped behavior and failures in working memory, conceptualization
      and learning. The results allowed preliminary norms to be defined for elderly AD
      patients on the various WCST indicators, grading their performance in eight
      diagnostic areas and yielding the identification of different levels of
      impairment of executive functions in these elderly patients. Conclusions: The
      results demonstrated specific aspects of performance on the WCST by elderly
      people with AD, highlighting the effect of the disease on cognitive performance
      and executive functioning. Those normative references, although preliminary make
      a significant contribution to the neuropsychological assessment of AD patients in
      the Brazilian context, within the informative scope of the WCST.

PMID- 29213387
TI  - Behavior disorders and subjective burden among caregivers of demented patients.
AB  - : Many patients with dementia live within the community supported by their family
      and friends. Majority of patient caregivers suffer from high levels of stress.
      Methods: A quasi-experimental study, which compared the effects of nursing
      interventions on behavior disorders in both patients with moderate to severe
      dementia and their caregivers, followed over 18 months. The assessments were
      performed at the outpatient clinic of the Federal University of Sao Paulo and
      again at patients' homes with their primary caregiver, after informed consent
      form. Measurements were performed at baseline and after 18 months (pre and post
      test). The instruments used were: The CDR, NPI and NPI-D; Katz Index and FAQ.
      Simultaneously, caregivers were enrolled onto the Dementia Education Program.
      Results: The final sample was composed of 31 subjects, having a mean age of 77.4
      y.o. (+/-8 SD). Nursing interventions were effective in reducing some of the
      behavioral disturbances (Z= -3.1; p=0.002), such as Aggression (Z= -3.7; p<0.001)
      and anxiety (Z= -2.3; p=0.023). Caregiver distress also reduced upon
      interventions (Z= -2.2; p=0.030). Conclusion: Our results indicate nursing
      interventions may be effective in reducing the frequency and severity of
      behavioral disorders and subjective burden among caregivers. Education Programs
      can improve caregiver burden through conveying information on difficulties
      related to the disease and how to deal with them.

PMID- 29213388
TI  - Support groups for caregivers of patients with Dementia: A comparative study.
AB  - : Since the dementias lead to the need for caregivers, a Group for Dementia
      Caregivers (GC) was set up where the present study compared the psychosocial
      characteristics, quality of life and caregiver overload in a Group For Dementia
      Caregivers (GC) with caregivers not involved in this scheme (non-GC). Methods: 19
      primary caregivers counseled by this group (GC group) was studied and compared to
      a group of 13 caregivers not receiving such counseling (non-GC group). The
      instruments used were the World Health Organization Quality of Life (WHOQOL
      bref), the State-Trait Anxiety Inventory (STAI) and Caregiver Load Scale (CLS).
      Results: The two groups did not differ in mean age or gender (P<0.05). GC
      caregivers had a higher educational level, were service workers where majority
      were the children of patients. In the Non-CG group, the most frequent occupation
      was housewife, with most subjects being spouses. The WHOQOL revealed a
      significant difference (p<0.05) between groups in the physical, social relations
      and environment domains (GC>Non-GC). The STAI revealed a significant difference
      (p<0.05) in the Trait subscale (GC>Non-GC), but not in the State subscale. There
      was no significant difference in CLS. Conclusion: The GC appeared to be of
      benefit to its participants, with probable positive repercussions on the
      patients, particularly regarding their quality of life.

PMID- 29213389
TI  - Verbal and non-verbal semantic impairment: From fluent primary progressive
      aphasia to semantic dementia.
AB  - : Selective disturbances of semantic memory have attracted the interest of many
      investigators and the question of the existence of single or multiple semantic
      systems remains a very controversial theme in the literature. Objectives: To
      discuss the question of multiple semantic systems based on a longitudinal study
      of a patient who presented semantic dementia from fluent primary progressive
      aphasia. Methods: A 66 year-old woman with selective impairment of semantic
      memory was examined on two occasions, undergoing neuropsychological and language
      evaluations, the results of which were compared to those of three paired control
      individuals. Results: In the first evaluation, physical examination was normal
      and the score on the Mini-Mental State Examination was 26. Language evaluation
      revealed fluent speech, anomia, disturbance in word comprehension, preservation
      of the syntactic and phonological aspects of the language, besides surface
      dyslexia and dysgraphia. Autobiographical and episodic memories were relatively
      preserved. In semantic memory tests, the following dissociation was found:
      disturbance of verbal semantic memory with preservation of non-verbal semantic
      memory. Magnetic resonance of the brain revealed marked atrophy of the left
      anterior temporal lobe. After 14 months, the difficulties in verbal semantic
      memory had become more severe and the semantic disturbance, limited initially to
      the linguistic sphere, had worsened to involve non-verbal domains. Conclusions:
      Given the dissociation found in the first examination, we believe there is
      sufficient clinical evidence to refute the existence of a unitary semantic
      system.

PMID- 29213390
TI  - Brazilian adaptation of the Addenbrooke's Cognitive Examination-Revised (ACE-R).
AB  - : The Addenbrooke's Cognitive Examination-Revised (ACE-R) is a highly sensitive
      and specific tool for the detection of mild dementia. It is particularly useful
      in differentiating Alzheimer's disease from frontotemporal dementia. While the
      first version of the test battery has been adapted in many countries, its revised
      version has not, probably because it was published very recently. Objective: To
      translate and adapt the ACE-R for use in the Brazilian population. Methods: Two
      independent translations were made from English into Portuguese, followed by two
      independent back-translations. Few adaptations in accordance to the Brazilian
      culture and language were made and a first version of the instrument produced.
      This former version of the ACE-R was administered to 21 cognitively healthy
      subjects aged 60 years or more, with different educational levels. Results: The
      mean age of the studied sample of healthy elderly was 75.4 years (ranging from 60
      to 89 years). Small additional modifications were necessary after the evaluation
      of the first ten subjects in order to improve comprehension of the test. The
      final Portuguese version of the ACE-R was produced and was found to be well
      understood by the remaining 11 subjects, taking an average of 15 minutes to be
      administered. Conclusions: The Brazilian version of the ACE-R proved to be a
      promising cognitive instrument for testing both in research and clinical
      settings. With this regard, additional studies are currently being carried out in
      our unit in order to investigate the diagnostic properties of the ACE-R in our
      milieu.

PMID- 29213391
TI  - Evaluation of artwork produced by Alzheimer's disease outpatients in a pilot art
      therapy program.
AB  - : The use of art as therapy for patients with Alzheimer's disease is
      characterized by the opportunity of art expression and is conducted with
      therapeutic purposes. Art in the context of dementia provides a unique window
      into the cognitive processes of various brain regions. Objective: To evaluate
      association between the severity of cognitive deficit and artwork (type,
      material, and quality) produced by AD patients in a pilot program. Methods:
      Eleven patients were evaluated in a weekly quasi-experiment study following 125
      sessions of art therapy over a period of 31 months. Patients were diagnosed with
      Alzheimer's disease (N=11) according to standard criteria. The Mini Mental State
      Examination and a battery of cognitive tests were used to assess cognitive
      deficit. Results: Different types of artwork were observed during the sessions
      for most patients. The selection of drawing or modeling showed significant
      association with severity of cognitive deficit. Type of material, as well as
      quality of artwork, also showed a similar association with deficit severity.
      Conclusion: The significant association between type of work, drawing or
      modeling, with severity of cognitive impairment could be influenced by a range of
      damaged cognitive functions (including visuospatial), and by inadequate
      perception of graphic elements.

PMID- 29213392
TI  - Creutzfeldt-Jakob disease associated with a missense mutation at codon 200 of the
      prion protein gene in Brazil.
AB  - Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases,
      and its clinical picture may be either indistinguishable from that of sporadic
      CJD (sCJD) or be atypical, usually with younger onset and longer duration. We
      report a case of 59-year old Brazilian man who presented rapidly progressive
      cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A
      brother and a cousin of the patient had CJD. A point mutation at codon 200
      (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months
      after onset of symptoms. Autopsy was not performed. The clinical presentation of
      gCJD associated with E200K, which is the most frequent PRNP mutation, is quite
      similar to sCDJ. This is the first report of E200K mutation in Brazil, and it is
      possible that a more systematic search for its occurrence may show it to be
      relatively frequent in Brazil.

PMID- 29213393
TI  - Editorial.

PMID- 29213394
TI  - Ethical aspects of brain death and end-of-life.
AB  - Ethical issues surrounding brain death and end-of-life have not been afforded in
      Brazil the same attention as in many developed countries. There appears to be
      reluctance on the part of Brazilian doctors to limit or suspend procedures or
      treatment which prolongs life of patients in terminal phases of severe incurable
      illness, or to suspend the artificial means of supporting vegetative functions in
      cases of brain death outside the context of organ and tissue donation for
      transplant. Fears grounded in possible administrative (Regional Medical Councils)
      or legal repercussions, as well as ambiguous interpretations of religious
      precepts, partially explain this reluctance which often results in unnecessary
      prolonging of patient suffering. A recent resolution by the Federal Medical
      Council on end-of-life may offer doctors some guidance and confidence in dealing
      with highly complex ethical situations.

PMID- 29213396
TI  - Paraconsistent artificial neural networks and Alzheimer disease: a preliminary
      study.
AB  - : EEG visual analysis has proved useful in aiding AD diagnosis, being indicated
      in some clinical protocols. However, such analysis is subject to the inherent
      imprecision of equipment, patient movements, electric registers, and individual
      variability of physician visual analysis. Objectives: To employ the
      Paraconsistent Artificial Neural Network to ascertain how to determine the degree
      of certainty of probable dementia diagnosis. Methods: Ten EEG records from
      patients with probable Alzheimer disease and ten controls were obtained during
      the awake state at rest. An EEG background between 8 Hz and 12 Hz was considered
      the normal pattern for patients, allowing a variance of 0.5 Hz. Results: The PANN
      was capable of accurately recognizing waves belonging to Alpha band with
      favorable evidence of 0.30 and contrary evidence of 0.19, while for waves not
      belonging to the Alpha pattern, an average favorable evidence of 0.19 and
      contrary evidence of 0.32 was obtained, indicating that PANN was efficient in
      recognizing Alpha waves in 80% of the cases evaluated in this study. Artificial
      Neural Networks - ANN - are well suited to tackle problems such as prediction and
      pattern recognition. The aim of this work was to recognize predetermined EEG
      patterns by using a new class of ANN, namely the Paraconsistent Artificial Neural
      Network - PANN, which is capable of handling uncertain, inconsistent and
      paracomplete information. An architecture is presented to serve as an auxiliary
      method in diagnosing Alzheimer disease. Conclusions: We believe the results show
      PANN to be a promising tool to handle EEG analysis, bearing in mind two
      considerations: the growing interest of experts in visual analysis of EEG, and
      the ability of PANN to deal directly with imprecise, inconsistent, and
      paracomplete data, thereby providing a valuable quantitative analysis.

PMID- 29213395
TI  - Systematic review of dementia prevalence 1994 to 2000.
AB  - : Ageing has occurred in all regions of the world, with impact on
      neuropsychiatric disorders, particularly dementia. However, previous meta
      analysis and reviews have shown high variability in world dementia prevalence
      rates. Objective: The aim of this study was to perform a wide-ranging review of
      the dementia prevalence studies published in recent years. Methods: The search
      was made on Medline, Lilacs and Embase databases for research conducted between
      1994 and 2000. The main inclusion criteria were: use of standard diagnostic
      criteria and investigation of community samples. Results: The final selection
      included 42 papers, from all continents. The mean prevalence rate of dementia in
      subjects aged 65 years and older, for continents, ranged from 2.2% in Africa to
      8.9% in Europe, and among countries, from 1.3% in India to 14.9% in Spain.
      However, there was a trend of clustering of the world prevalence rates with the
      majority of studies reporting rates between 4.2% and 7.2% (>=65 years). Age
      directly influenced the rates, with a mean prevalence rate of 1.2% (95% CI:
      0.8.1.5) for the 65-69 years group and 39.9% (95% CI: 34.4.45.3) for the 90-94
      year group, but showing less pronounced influence in the very elderly age group.
      The urban samples had higher rates, where no significant gender difference was
      evidenced. Conclusion: The age influence over dementia rates apparently leveled
      off in the very elderly group while a trend toward similar dementia prevalence
      rates around the world was probably influenced by greater homogeneity in
      diagnostic criteria.

PMID- 29213397
TI  - Mini-Mental State Examination and proton spectroscopy of the posterior cingulate
      in Alzheimer disease.
AB  - : To compare metabolite ratios in the posterior cingulate with the Mini-Mental
      State Examination (MMSE) test scores in patients with mild or moderate Alzheimer
      disease and in controls. Methods: We evaluated 29 patients with mild or moderate
      Alzheimer disease and 15 controls by proton spectroscopy with the voxel located
      in the posterior cingulate. The MMSE was applied to all patients and controls.
      The metabolic ratios: N-acetyl-aspartate/creatine (Naa/Cr), mio-inositol/creatine
      (mI/Cr) and mio-inositol/N-acetyl-aspartate (mI/Naa) were obtained and then post
      processed using the MRUI software (magnetic resonance user interface). Results:
      Correlation between Naa/Cr and mI/Naa ratios in the posterior cingulate with the
      MMSE was observed, and a positive correlation with Naa/Cr and negative
      correlation with mI/Naa were seen. The mI/r ratio presented no correlation with
      MMSE scores. Conclusion: The positive correlation with Naa/Cr, and negative
      correlation with mI/Naa may corroborate that neuronal density/viability is
      associated to a higher MMSE score.

PMID- 29213399
TI  - Sensitivity and applicability of the Brazilian version of the Brief Assessment of
      Cognition in Schizophrenia (BACS).
AB  - : Cognitive assessment in schizophrenia has traditionally used batteries that are
      long and complex or differ widely in their content. The Brief Assessment of
      Cognition in Schizophrenia (BACS) has been developed to cover the main cognitive
      deficits of schizophrenia as well as to be easily and briefly administered,
      portable, sensitive and reliable. Objectives: To investigate the applicability
      and sensitivity of the Brazilian Version of the BACS (Brazilian-BACS). Methods:
      Performance of 20 stable patients with schizophrenia on the Brazilian-BACS was
      compared to 20 matched healthy controls. Results: Applying the Brazilian-BACS
      required 43.4+/-8.4minutes for patients and 40.5+/-5.7 minutes for controls
      (p=0.17). All tests demonstrated significant differences between controls and
      patients (P<0.01). Pearson's correlation analysis and Cronbach's a evidenced a
      high internal consistency for patient performance. The cognitive deficit in the
      patients was approximately 1.5 standard deviations below controls. These results
      were consistent with those reported in the validation of the original version and
      in meta-analyses of similar studies. Conclusions: The Brazilian-BACS displayed
      good applicability and sensitivity in assessing the major cognitive constructs
      that are impaired in schizophrenia. Thus, the Brazilian-BACS seems to be a
      promising tool for assessing cognition in patients with schizophrenia in Brazil.

PMID- 29213398
TI  - Prevalence of hearing impairment in patients with mild cognitive impairment.
AB  - : The correlation between hearing and cognition is well established in dementia,
      but not in mild cognitive impairment (MCI). Objective: The aim of the present
      study was to define the prevalence of hearing impairment in elderly patients with
      MCI and in controls. Methods: Twenty-nine patients with MCI and 24 control
      subjects were analyzed. We evaluated memory and hearing impairments through
      clinical tests, including the Mini Mental Status Examination, Clinical Dementia
      Rating (CDR) and Hearing Handicap Inventory for the Elderly Screening (HHIE-S).
      Audiometries were performed in 22 patients with MCI and 19 subjects in a control
      group. Results: MCI patients showed more hearing complaints (68.9%) compared to
      the control group (25%) (p=0.001). No differences in the intensity of hearing
      complaints, measured by the HHIE-S, were detected. Nonetheless, differences
      between mean hearing threshold (MCI group=23.4+/-11.3dB and control group=16.0+/
      10.1dB) (p=0.03) were identified. Conclusions: There is a significant association
      between MCI and hearing impairment. Hearing impairment in MCI patients may be a
      contributory factor to cognitive decline. This may however be related to the same
      neuropathological process, due to lesions of cortical areas related to hearing.
      The early diagnosis of hearing impairment in MCI patients may offer a more
      appropriate approach to this disease.

PMID- 29213400
TI  - Right hemisphere damage: Communication processing in adults evaluated by the
      Brazilian Protocole MEC - Bateria MAC.
AB  - : Right-brain-damaged individuals may present discursive, pragmatic, lexical
      semantic and/or prosodic disorders. Objective: To verify the effect of right
      hemisphere damage on communication processing evaluated by the Brazilian version
      of the Protocole Montreal d'Evaluation de la Communication (Montreal
      Communication Evaluation Battery) - Bateria Montreal de Avaliacao da Comunicacao,
      Bateria MAC, in Portuguese. Methods: A clinical group of 29 right-brain-damaged
      participants and a control group of 58 non-brain-damaged adults formed the
      sample. A questionnaire on sociocultural and health aspects, together with the
      Brazilian MAC Battery was administered. Results: Significant differences between
      the clinical and control groups were observed in the following MAC Battery tasks:
      conversational discourse, unconstrained, semantic and orthographic verbal
      fluency, linguistic prosody repetition, emotional prosody comprehension,
      repetition and production. Moreover, the clinical group was less homogeneous than
      the control group. Conclusions: A right-brain-damage effect was identified
      directly, on three communication processes: discursive, lexical-semantic and
      prosodic processes, and indirectly, on pragmatic process.

PMID- 29213401
TI  - The influence of schooling on working memory performance in elderly individuals
      without cognitive decline.
AB  - : Over recent decades, research on cognition has been developed rapidly toward
      better understanding the cognitive changes that usually occur during normal
      aging. There is evidence that elderly individuals have worse working memory
      performance than young adults. However, the effect of education on this cognitive
      function remains unclear. Objectives: To analyze the performance of healthy
      elderly subjects on working memory tasks and to verify the influence of
      educational level on this performance. Methods: Forty elderly individuals without
      cognitive impairment and fully independent, were randomly chosen from a group of
      subjects participating in cultural activities at the university campus. The Digit
      Span Forward (DSF) test was used to evaluate attention performance. The working
      memory performance was assessed by the Digit Span Backward (DSB) and the
      difference between DSF and DSB. The data were statistically analyzed using the
      Spearman's correlation coefficient to verify the correlation between the Digit
      Span (DS) scores and the variables age and schooling, while the Multiple Linear
      Regression Model was used to verify the effect of these variables on the DS
      scores. Results: A significant positive correlation (r=0.41, p<0.01) as well as a
      significant association (beta=0.506; p=0.001; CI 95%= 0.064/0.237) were found
      between years of schooling and DSB scores. It was not observed statistical
      correlation (r= -0.08, p=0.64) or association (beta=0.41; p=0.775; CI 95%= 
      0.049/0.065) between age and DSB scores. Conclusion: In this study, higher levels
      of schooling were associated with better working memory performance in
      cognitively healthy elders.

PMID- 29213402
TI  - The Dementia Rating Scale (DRS) in the diagnosis of vascular dementia.
AB  - : The Dementia Rating Scale (DRS) is considered a very useful instrument to
      assess patients with dementia. The tasks are grouped into five subscales, each
      one evaluating different cognitive areas, namely: Attention,
      Initiation/Perseveration (I/P), Construction, Conceptualization and Memory.
      Objective: To verify the ability of the DRS in discriminating vascular dementia
      (VaD) patients from healthy controls and VaD from Alzheimer disease (AD)
      patients. Methods: The DRS was applied to 68 patients with mild dementia (12 with
      VaD and 56 with AD) and 60 healthy controls. The clinical diagnosis was made by
      two neurologists based on the patients' history, laboratory and neuroimaging
      results and neuropsychological tests. Results: In the comparison between VaD
      patients and controls, the subscales I/P, Memory, Conceptualization and Attention
      were those displaying best discrimination between the two groups. The cutoff <124
      yielded 93.3% of sensitivity and 91.7% of specificity for the diagnosis of VaD.
      Only the I/P subscale differentiated VaD from AD patients. Conclusions: The DRS
      was found to be a useful instrument to discriminate VaD patients from controls.
      VaD patients showed worse performance in tasks of executive functions than AD
      patients. Executive dysfunction, evaluated through the I/P subscale of the DRS,
      might be useful in differentiating between VaD and AD patients.

PMID- 29213403
TI  - The daily life of patients with dementia: A comparative study between the
      information provided by the caregiver and direct patient assessment.
AB  - : The functionality concept is very important, as the diagnosis of dementia
      presupposes the existence of functional impairment. Instruments assessing
      functional performance present some limitations. In most cases, the assessment is
      based on the caregiver's report. Some studies in international literature have
      evaluated this issue and concluded that a difference exists between the
      caregiver's report and direct patient assessment. American and European
      caregivers tend to underestimate the patient's functional limitations. However,
      this issue has hitherto not been investigated in our context. Objective: To
      compare the caregiver's information with direct assessment of the patient's
      performance based on the same functional assessment questionnaire. Methods:
      Seventy-two patients and caregivers were attended by the Occupational Therapy
      service of the Behavioral Neurology Outpatient Clinic between 1999 and 2001, 25
      of whom fulfilled the inclusion criteria: having a confirmed diagnosis of
      dementia according to the DSM-IV; having attended three or more return
      appointments, and where the caregiver belonged to the patient's family nucleus.
      The remaining subjects were excluded because of non-adherence to treatment or
      refusal to participate in the study. The Functional Activities Questionnaire by
      Pfeffer et al., 1982 was applied to patients in a laboratory simulation, while
      another evaluator interviewed the respective caregivers. The data were analyzed
      based on the weighted Kappa coefficient, and Wilcoxon test. Results: There were
      significative differences between caregiver's answers and direct observation of
      the patient's performance. The information provided by the caregivers proved
      unreliable since caregivers underestimated the patient's functional capacity.

PMID- 29213404
TI  - Clinical evaluation of patients with moderate to severe Alzheimer disease.
AB  - : Today, Alzheimer disease has become a serious risk to individual and public
      health, due to the significant incapacity it causes patients, its influence on
      family members and caregivers, along with the ensuing direct and indirect costs.
      Objectives: To build the profile of patients with moderate/severe AD, in the
      Geriatric Clinic Service of Cognitive Alterations of the Medical School at
      Universidade de Sao Paulo, by studying demential and comorbidity conditions and
      the degree of effectiveness of the therapies applied. Methods: 30 patients with
      moderate or severe AD were selected, (77.8+/-7.29 years). Age, sex, schooling,
      prevalent comorbidities/treatments and respective clinical-laboratorial
      effectiveness were analyzed. Instruments were applied to evaluate the cognitive
      and behavioral condition and dementia control therapies. Results: Most frequent
      comorbidities were arterial hypertension (80%) and diabetes (43.3%). A maximum
      dose of rivastigmine was observed in 43% of the patients, where 76% experienced
      adverse effects. Severe patients presented more cases of uncontrolled
      comorbidities, such as hypertension (P<0.001), as well as more behavioral
      alterations (P<0.001) and functional loss (P=0.004). Patients with greater
      behavioral alterations proved to be more functionally dependent (P=0.002), having
      less comorbidity control (P=0.004). Conclusions: In this population, a high
      incidence of comorbidities, frequent behavioral alterations and difficulties in
      therapy management were noted due to the severity of the dementia condition. New
      therapies for more adequate control of severe dementia should be studied.

PMID- 29213405
TI  - Comprehensive geriatric assessment in elderly outpatients with dementia.
AB  - : Dementia is a common disabling disease in the elderly. In such patients,
      general health conditions may worsen the functional decline and loss of autonomy.
      The Comprehensive Geriatric Assessment (CGA) is a validated and recommended
      instrument for multidimensional evaluation of the aged. Nonetheless, it has yet
      to be assessed in demented patients. Objectives: To analyze the functional,
      emotional and clinical status in elderly with dementia measured by the CGA. We
      also compared the results obtained in the same patients stratified for severity
      of dementia. Methods: Transversal study with demented elderly outpatients.
      Subjects were evaluated by the CGA consisting of clinical data, Clinical Dementia
      Rating, performance-oriented mobility assessment of gait and balance (POMA),
      Cornell scale for depression, activities of daily living, Mini Mental Status
      Examination (MMSE), Mini Nutritional Assessment, Whispered and Snellen Test.
      Results: Fifty-two patients with mean age of 77 years were evaluated. Majority of
      patients had Alzheimer disease (77%). Depression was the most prevalent
      comorbidity. The POMA score was related to the number of falls in the previous
      year. Also, there was correlation between complaints of visual and hearing
      impairment and the results on the Snellen and Whispered Tests. Regarding
      severity, 56% presented mild, 33% moderate and 11% severe condition. Patients
      with moderate/severe dementia had less leisure activities, greater risk of falls,
      along with worse performance on the MMSE, POMA and activities of daily living.
      Conclusions: The CGA was applied in demented elderly with the help of their
      caregivers, and was able to better characterize patient state of health. Subjects
      with moderate/severe dementia obtained poor results in several assessed criteria.

PMID- 29213407
TI  - Ten years of the Brazilian Researchers' Meeting on Alzheimer's Disease and
      Related Disorders.

PMID- 29213406
TI  - The syndrome of progressive posterior cortical dysfunction: A multiple case study
      and review.
AB  - : Dementia presenting with prominent higher order visual symptoms may be observed
      in a range of neurodegenerative conditions and is often challenging to diagnose.
      Objectives: To describe cases of progressive dementia presenting with prominent
      visual cortical symptoms. Methods: We conducted a retrospective search of cases
      of progressive dementia with predominant visual symptoms, seen at our dementia
      unit from 1996 to 2006. Results: Twelve patients (5 men, 7 women) were
      identified, with ages ranging from 49 to 67 years. At the first examination, the
      duration of the symptoms ranged from one to ten years and the Mini-Mental State
      Examination scores from 7 to 27. Eleven patients presented with predominant
      visuospatial symptoms (partial or complete Balint syndrome) and one with
      visuoperceptive impairment. Other reported manifestations were: constructional
      apraxia in 11 patients, partial or complete Gerstmann syndrome in ten, ideomotor
      apraxia in nine, hemineglect or extinction in four patients, alien hand
      phenomenon in three, and prosopagnosia in one patient. Memory loss was reported
      by ten patients, but was not the main complaint in any of these cases. Insight
      was relatively preserved in five patients even after a long period following the
      onset of symptoms. Six patients developed parkinsonism during evolution. Clinical
      diagnoses were possible or probable AD in seven patients, cortico-basal
      degeneration in four, and dementia with Lewy body in one. Conclusions: Clinicians
      should consider this condition especially in presenile patients with slowly
      progressive higher-order visual symptoms. Although described in association with
      different conditions, it may also occur in Alzheimer disease.

PMID- 29213408
TI  - Neuroprotective actions of 2,4-dinitrophenol: Friend or foe?
AB  - 2,4-dinitrophenol (DNP) has long been known to be toxic at high concentrations,
      an effect related to uncoupling of mitochondrial oxidative phosphorylation. Five
      years ago, however, we reported that low concentrations of DNP protect neurons
      against the toxicity of the amyloid-beta peptide. Since then, a number of other
      studies have provided evidence of beneficial actions of DNP (at low
      concentrations), including neuroprotection against different types of insult,
      blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal
      differentiation, and even extension of lifespan in certain organisms. Some of
      these effects appear due to mild mitochondrial uncoupling and prevention of
      oxidative stress, whereas other actions are related to activation of additional
      intracellular signaling pathways. This study discusses the evidence supporting
      beneficial neuroprotective actions of DNP. DNP and other compounds with similar
      biological activities may be of interest in the development of novel therapeutic
      approaches for neurodegenerative diseases and other neurological disorders.

PMID- 29213409
TI  - New variant of Creutzfeldt-Jakob (vCJD) disease and other human prion diseases
      under epidemiological surveillance in Brazil.
AB  - To increase the timeliness of detection of human cases of the new variant of
      Creutzfeldt-Jakob disease (vCJD) and to reduce the risk of transmission, the
      Brazilian Ministry of Health has established and standardized rules and control
      measures. These include the definition of criteria for suspect cases, reporting,
      monitoring, and control measures for illness prevention and transmission.
      Guidelines to be used by the team of health care staff were published and
      distributed to health workers. A detailed proposal for a simplified system of
      surveillance for prion diseases was developed and mandatory reporting introduced.
      Additional effort is necessary to increase vCJD case detection, thus making it
      necessary to establish a partnership with health care services for best
      identification of suspected cases and dissemination of information to all
      involved in the service dealing with vCJD investigation.

PMID- 29213410
TI  - Prion diseases are undercompulsory notification in Brazil: Surveillance of cases
      evaluated by biochemicaland/or genetic markers from 2005 to 2007.
AB  - : The emergence of the new variant of Creutzfeldt-Jakob disease (vCJD) in the
      United Kingdom has raised concerns over the risks of this prion disease in other
      parts of the world. Since 2005, human prion diseases have been under compulsory
      notification in Brazil. It is well known that some polymorphisms within the
      cellular prion gene (PRNP) have been associated to a higher susceptibility to
      sporadic CJD (sCJD) and vCJD. Objectives: To describe the first notified cases
      and to evaluate the presence of mutations and polymorphisms of the PRNP in these
      cases. Methods: Thirty-five notified cases were evaluated by clinical, auxiliary
      exams and biochemical and/or genetic tests and classified according to the World
      Health Organization criteria for CJD. A control group (N=202) was included for
      the purpose of comparing the genetic analyses. Results: Twenty seven cases (74%)
      were classified as possible sCJD while 51% fulfilled the criteria for probable
      sCJD. Brain tissue analysis was available in three cases, where two were
      classified as definite sCJD and one as unconfirmed sCJD. Mutation of the PRNP was
      not found, and regarding the codon 129 polymorphism, valine in both alleles
      (Val129Val) was more frequent in patients than in the control group (OR=4.98;
      1.55-15.96; p=0.007) when all possible cases were included, but not when only
      probable cases were considered. Conclusions: Our data did not show correlation of
      PRNP polymorphisms with probable sCJD cases. It is necessary to work toward
      notification of all cases of possible CJD in Brazil and to increase the rate of
      definitive diagnoses.

PMID- 29213411
TI  - Clinicopathological correlates of Alzheimer's disease in a general autopsy series
      from Brazil.
AB  - : The current neuropathological staging models of Alzheimer's disease (AD) have
      been developed within the last 20 years. Nevertheless, they were mostly tested on
      Caucasians of Northern European ancestry or on Asians. Objective: To verify which
      of the accepted neuropathologic criteria best discriminates AD from normal aging
      in a well characterized Brazilian clinicopathological series. Methods: A random
      sample consisting of 89 subjects belonging to the Brazilian Brain Bank of the
      Aging Brain Study were clinically and neuropathologically fully assessed using
      immunohistochemistry. Clinical and functional statuses were assessed by
      interviewing a reliable informant. The Clinical dementia rating scale (CDR) was
      compared to Braak and Braak stage, the consortium to establish a registry for
      Alzheimer's disease (CERAD) score and NIA-Reagan (National Institute of Aging -
      Reagan Institute) score. Subjects with a neuropathologic diagnosis other then AD
      were excluded (n=27). Results: The CDR score distribution for the 62 selected
      subjects was as follows: CDR0=39, CDR0.5=9, CDR1=14. There were no differences
      regarding age, gender and education among the groups. CDR score correlated best
      with the CERAD score (r=0.5303; p<0.001) . Braak and Braak stage was
      significantly higher in subjects with higher CDR. Correlation of the NIA-Reagan
      criteria was partially disrupted because a large proportion of subjects did not
      fit any of its categories. Conclusions: In this series, CERAD criteria better
      correlated with the CDR groups. Consistent with earlier studies, some cognitively
      normal subjects have AD neuropathological diagnosis.

PMID- 29213412
TI  - Underdiagnosis of frontotemporal lobar degeneration in Brazil.
AB  - : Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative
      disorder that involves the frontal and anterior temporal lobes. It is
      characterized by prominent behavioral and language disorders. There are three
      variants of FTLD: frontotemporal dementia (FTD), semantic dementia (SD) and
      progressive non-fluent aphasia (PNFA). FTLD may be mistaken for AD (Alzheimer's
      disease) or psychiatric disorders especially in the early stages. Objectives: To
      describe the demographic characteristics of patients with FTLD, assessed at the
      Behavioral and Cognitive Neurology Unit, and to show that FTLD is commonly
      clinically under-diagnosed. Methods: All patients diagnosed with FTLD (Consensus
      Criteria for FTLD), and who were seen at the Behavioral and Cognitive Neurology
      Unit of Hospital das Clinicas, in Sao Paulo, Brazil from January 2004 to August
      2007 were included in the analyses. Results: Sixteen patients with FTLD (11
      women) were included in this study. There were 12 patients with FTD, two with
      PNFA and two with SD. The mean duration of the illness until diagnosis of FTLD
      was 4.1+/-2.3 years, ranging from one to seven years. Nine patients had been
      initially seen by psychiatrists, five by neurologists, and two by general
      physicians. The first diagnosis was psychiatric disorder in six patients, AD in
      four, dementia in two, FTD in two, and stroke and hydrocephalus for one patient
      each. Conclusion: The diagnosis of FTLD can be difficult and many patients may be
      misdiagnosed in Brazil, especially in the initial stages. Educational programs on
      FTLD for the medical community are warranted.

PMID- 29213413
TI  - Semantic dementia Brazilian study of nineteen cases.
AB  - : The term semantic dementia was devised by Snowden et al. in 1989 and nowadays,
      the semantic dementia syndrome is recognized as one of the clinical forms of
      frontotemporal lobar degeneration (FTLD) and is characterized by a language
      semantic disturbance associated to non-verbal semantic memory impairment.
      Objectives: The aim of this study was to describe a Brazilian sample of 19
      semantic dementia cases, emphasizing the clinical characteristics important for
      differential diagnosis of this syndrome. Methods: Nineteen cases with semantic
      dementia were evaluated between 1999 and 2007. All patients were submitted to
      neurological evaluation, neuroimaging exams and cognitive, language and semantic
      memory evaluation. Results: All patients presented fluent spontaneous speech,
      preservation of syntactic and phonological aspects of the language, word-finding
      difficulty, semantic paraphasias, word comprehension impairment, low performance
      in visual confrontation naming tasks, impairment on tests of non-verbal semantic
      memory and preservation of autobiographical memory and visuospatial skills.
      Regarding radiological investigations, temporal lobe atrophy and/or hypoperfusion
      were found in all patients. Conclusions: The cognitive, linguistic and of
      neuroimaging data in our case series corroborate other studies showing that
      semantic dementia constitutes a syndrome with well defined clinical
      characteristics associated to temporal lobe atrophy.

PMID- 29213414
TI  - Alzheimer's patients do not show left unilateral spatial neglect but exhibit
      peripheral inattention and simplification.
AB  - : The Rey-Osterrieth Complex Figure Test (RCFT) is widely used to measure
      visuoperceptual and visuoconstructional skills, while the Line Bisection (LB)
      test is commonly employed to assess unilateral spatial neglect (USN). Previous
      studies have suggested that Alzheimer's disease (AD) patients may suffer from
      left USN. Objectives: The purpose of this study was to clarify whether left USN
      occurs in AD. Methods: Forty controls, 40 very mild AD patients and 31
      mild/moderate AD patients performed both the RCFT copying and the LB test.
      Results: The very mild AD and mild/moderate AD groups had lower total RCFT
      copying scores and also scored lower in the "left" and "detail" categories
      compared to controls. However, there were no correlations between the left
      category score for RCFT and the LB score. Instead, peripheral inattention and
      simplification patterns were noted. Conclusions: We found that the RCFT copying
      test is effective for detecting early AD and suggest that AD patients manifest
      peripheral inattention and simplification but not left USN.

PMID- 29213415
TI  - Semantic, phonologic, and verb fluency in Huntington's disease.
AB  - : Verbal fluency tasks have been identified as important indicators of executive
      functioning impairment in patients with frontal lobe dysfunction. Although the
      usual evaluation of this ability considers phonologic and semantic criteria,
      there is some evidence that fluency of verbs would be more sensitive in
      disclosing frontostriatal physiopathology since frontal regions primarily mediate
      retrieval of verbs. Huntington's disease usually affects these circuitries.
      Objective: To compare three types of verbal fluency task in the assessment of
      frontal-striatal dysfunction in HD subjects. Methods: We studied 26 Huntington's
      disease subjects, divided into two subgroups: mild (11) and moderate (15) along
      with 26 normal volunteers matched for age, gender and schooling, for three types
      of verbal fluency: phonologic fluency (F-A-S), semantic fluency and fluency of
      verbs. Results: Huntington's disease subjects showed a significant reduction in
      the number of words correctly generated in the three tasks when compared to the
      normal group. Both controls and Huntington's disease subjects showed a similar
      pattern of decreasing task performance with the greatest number of words being
      generated by semantic elicitation followed by verbs and lastly phonologic
      criteria. We did not find greater production of verbs compared with F-A-S and
      semantic conditions. Moreover, the fluency of verbs distinguished only the
      moderate group from controls. Conclusion: Our results indicated that phonologic
      and semantic fluency can be used to evaluate executive functioning, proving more
      sensitive than verb fluency. However, it is important to point out that the
      diverse presentations of Huntington's disease means that an extended sample is
      necessary for more consistent analysis of this issue.

PMID- 29213416
TI  - Sentence comprehensionin Parkinson's disease.
AB  - : Parkinson's disease (PD) patients with dementia have impairment of syntactic
      comprehension. Non-demented PD patients also experience difficulties in sentence
      comprehension and can be particularly impaired in the processing of grammatical
      characteristics of syntactically complex sentences. Objective: The aim of this
      study was to verify the performance of PD patients without dementia in a
      syntactic comprehension task compared with normal elderly. Methods: We studied
      oral sentence comprehension in fourteen patients with idiopathic PD together with
      fourteen controls matched for age and education, using the Token Test and
      Schmitt's Syntactic Comprehension Test (developed in Brazilian Portuguese).
      Results: For the Token Test, there was no statistically significant difference
      between the PD group and the control group, whereas on the Syntactic
      Comprehension Test there was a slight statistically significant difference
      between the groups only for relatives in subject clauses (p=0.0407). Conclusions:
      PD patients differed from controls in the oral comprehension for relatives
      subject sentences alone. These results did not strictly reproduce those
      previously reported in the literature, and therefore point to the need for
      creating tests with diverse syntactic constructions in Portuguese able to produce
      consistent data regarding language behavior of Brazilian subjects with PD in
      comprehension tasks.

PMID- 29213417
TI  - Spatial working memory in Alzheimer's disease: A study using the Corsi block
      tapping test.
AB  - : The Corsi block-tapping test was developed as a non-verbal task to measure
      spatial memory. In this test, cubes are tapped by the examiner in novel sequences
      of increasing length after which participants are required to reproduce each
      sequence immediately. Objectives: To evaluate spatial working memory in
      Alzheimer's disease (AD) patients. Methods: 30 elderly control subjects (21
      women, 9 men) and 30 patients with probable Alzheimer's disease (15 women and 15
      men), with 8 or more years of schooling, were evaluated with the Mini-Mental
      State Examination (MMSE), digit span and Corsi block-tapping test. Proportions
      were compared using Chi-Square, and continuous variables with the Mann-Whitney
      tests. Results: AD patients were older than controls (p=0.014), but there were no
      differences regarding gender or educational level between these groups. The
      performance on the Corsi block-tapping test differed between AD and control
      individuals (p=0.010), and between patients with moderate dementia and controls
      (p=0.032), but not between control individuals and patients with mild dementia
      (p=0.090). Conclusions: In the present study, AD patients with moderate dementia
      showed impairment in spatial working memory while those with mild dementia did
      not. This finding may be due to the relatively small sample size, but it is also
      possible that spatial memory may be normal in the initial (limbic) phase of AD.

PMID- 29213418
TI  - Performance of elderly on the three words-three shapes test: a Brazilian study.
AB  - : The three words-three shapes test is a brief bedside technique for assessment
      of learning and memory using verbal and non-verbal material. To the best of our
      knowledge, performance of Brazilian elderly on this test has not yet been
      reported. Objective: To evaluate the performance of normal Brazilian elderly on
      the three words-three shapes test. Method: A total of 50 adult patients, 25 males
      and 25 females, with age ranging from 55 to 81 years (66.0+/-7.10 years), 1 to 8
      years of schooling, different economic conditions and living in the Sao Jose do
      Rio Preto municipality, State of Sao Paulo, were evaluated. Results: There was no
      statistically significant difference between performance of males and females.
      Performance on incidental recall was significantly lower than in delayed recall.
      The performance in the learning phase improved following at least two further
      presentations of the stimuli. Approximately 50% of the participants did not
      remember the six stimuli and had to proceed to the recognition stage. The
      performance in the recognition stage was significantly better than during
      spontaneous recall. Patients with low educational level (less years of schooling)
      had poorer performance on the recall of shapes and on the total score of the
      test. Conclusions: The three words-three shapes test is rapid, efficient and
      straightforward to apply in the elderly, but low educational level was associated
      with poorer performance on this test. Normal elderly individuals had greater
      difficulty in the encoding process and in searching for stored information.

PMID- 29213419
TI  - Evaluation of clinical comorbidities in cognitively impaired patients with
      depressive symptoms.
AB  - : In demented patients, depressive symptoms as well as cognition and clinical
      comorbidities can interact and induce a complex condition of severity and
      handicap. Objective: The objective of this study was to evaluate the influence of
      depressive symptoms in cognitively impaired patients on associated clinical
      comorbidities in geriatric patients. Methods: One-hundred-thirty-eight (138)
      patients were divided into two groups: the first contained cognitively impaired
      patients with depressive symptoms while the second comprised cognitively impaired
      patients without depressive symptoms. To quantify comorbidities, the Modified
      CIRS Scale was used. Results: Out of the 138 patients, 52 were cognitively
      impaired with depressive symptoms and 86 were cognitively impaired without
      depressive symptoms, both having mean CDR of 1.74 (moderate dementia). The
      patients with depressive symptoms used more drugs (4.98 per patient vs. 3.45 per
      patient without depressive symptoms; p=0.001), presented more comorbidities (3.24
      per patient vs. 2.46 per patient without depressive symptoms; p=0.009). However,
      these comorbidities were neither more severe nor more complex in the patients
      with depressive symptoms, with mean Comorbidity Severity Index of 1.45 in
      patients with and 1.37 in patients without depressive symptoms (p= 0.078) and
      mean Comorbidity Complexity Index of 2.41 in patients with depressive symptoms
      and 2.01 in those without depressive symptoms (p=0.103). Conclusion: Cognitively
      impaired patients with depressive symptoms had a greater absolute number of
      comorbidities and took more drugs although these comorbid diseases were less
      severe and complex than in non-depressive cognitively impaired patients.

PMID- 29213420
TI  - Neuropsychological rehabilitation in a patient with ruptured anterior
      communicating artery aneurysm: 48 month outcomes.
AB  - : The neurobehavioral impairments associated with aneurysms of the anterior
      communicating artery (ACoA) are severe amnesia, executive problems and
      personality changes. Although most patients achieve a favorable neurological
      outcome, those cognitive deficits usually prevent return to previous activities
      and levels of social integration. Objectives: To report the outcomes of a
      neuropsychological and behavioral intervention in a 55 year-old man with very
      severe memory and executive dysfunctions following ACoA aneurysm rupture.
      Methods: Neuropsychological intervention focused in functional adjustment in
      everyday life was used, including individual sessions with the patient,
      discussion sessions with caregivers and also work with patient at home, aiming
      generalization of the rehabilitation strategies. Neuropsychological and
      functional assessments were conducted pre and post intervention. Results:
      Important improvements were seeing in behavior and daily living performance after
      treatment. Conclusions: A neuropsychological rehabilitation approach focused on
      goals based on the family and caregivers necessities is an efficient manner in
      which to carry out cognitive rehabilitation in severe cases. The importance of a
      supportive family should be stressed.

PMID- 29213421
TI  - Profile of caregivers of Alzheimer's disease patients attended at a reference
      center for cognitive disorders.
AB  - : This is a study on burden of caregivers of patients with Alzheimer's disease
      attended at a Reference Center for Cognitive Disorders. Objective: To evaluate
      the profile and burden on caregivers of patients with Alzheimer's disease
      attended at a Reference Center for Cognitive Disorders. Methods: We collected
      demographic information and data on the relationship with the patient from
      caregivers, and measured burden with the Zarit scale. The patients were evaluated
      with the following scales: the Cambridge Cognitive Test (CAMCOG); Mini Mental
      State Examination, the Neuropsychiatric Inventory for neuropsychiatry symptoms,
      and Functional Activities Questionnaire - FAQ for functional impairment. Results:
      Of the 31 caregivers, 77.4% were female, predominantly, and daughters, having a
      mean age of 58.6 years, educational level of 8.1 years, 70% of caregivers co
      resided with the patient and 71% did not work. The mean time as a caregiver was 3
      years. Twenty-seven percent of the caregivers presented mild to severe burden.
      The variables presenting significant association with caregiver burden were
      scores on the NPI and CAMCOG. Conclusion: The social demographic characteristics
      of the sample were similar to those of studies performed in other countries. The
      average time as a caregiver and the frequency of caregivers with mild to intense
      burden were lower than those reported in international studies. Neuropsychiatric
      symptoms and severity of cognitive decline were the main factors associated to
      burden in this sample of mostly mild to moderate demented AD patients. Further
      studies are necessary to verify whether the burden is indeed less intense in our
      milieu.

PMID- 29213422
TI  - Alien hand syndrome in AIDS: Neuropsychological features and physiopathological
      considerations based on a case report.
AB  - Alien hand syndrome consists of an autonomous motor activity perceived as an
      involuntary yet purposeful movement, with a feeling of foreignness of the
      involved limb, commonly associated with a failure to recognize ownership of the
      limb in the absence of visual cues. A 41 year old left-handed woman, HIV
      positive, evolved with loss of control in the left hand. Her left hand presented
      extravolitional movements, as if having a will of its own, not responding to
      commands such as opening a door or holding an umbrella, but instead groping
      unneeded objects. She had talked to her hand and even fought it. In addition,
      other clinical presentations including recent memory loss, hemineglect and
      dysphoria were observed. Computed tomography revealed a hypodensity area in the
      right frontal-parietal region, with midline deviation. Considering clinical and
      epidemiological data, the diagnosis of Central Nervous System (CNS) toxoplasmosis
      was reached. No previous reports showing association among AIDS, toxoplasmosis
      and alien hand syndrome were found.

PMID- 29213423
TI  - In the March 2016 issue.

PMID- 29213425
TI  - Phototest for neurocognitive screening in multiple sclerosis.
AB  - : Multiple Sclerosis (MS) is one of the most common neurological disorders.
      Cognitive dysfunction is considered a clinical marker of MS, where approximately
      half of patients with MS have cognitive impairment. Objective: The Phototest (PT)
      is a brief cognitive test with high diagnostic sensitivity, accuracy and cost
      effectiveness for detecting cognitive deterioration. Our aim was to test the
      utility of the PT as a neurocognitive screening instrument for MS. Methods: The
      study enrolled 30 patients with different types of MS from an outpatient clinic
      as well as 19 healthy participants. In conjunction with the PT, the Montreal
      Cognitive Assessment (MoCA), Barthel Index (BI), Expanded Disability Status Scale
      (EDSS), and Fatigue Severity Scale (FSS) were administered. Results: The MS group
      obtained significantly lower results on all domains of the PT, except for the
      naming task. The PT showed good concurrent validity with the MoCA. In direct
      comparison to the MoCA, PT showed a greater area under the curve and higher
      levels of sensitivity and specificity for MS neurocognitive impairments. A cut
      off score of 31 on the Phototest was associated with sensitivity of 100% and
      specificity of 76.7%. Conclusion: The PT is a valid, specific, sensitive and
      brief test that is not dependent on motor functions. The instrument could be an
      option for neurocognitive screening in MS, especially in identifying cases for
      further neuropsychological assessment and intervention.

PMID- 29213424
TI  - Causes, effects and connectivity changes in MS-related cognitive decline.
AB  - Cognitive decline is a frequent but undervalued aspect of multiple sclerosis
      (MS). Currently, it remains unclear what the strongest determinants of cognitive
      dysfunction are, with grey matter damage most directly related to cognitive
      impairment. Multi-parametric studies seem to indicate that individual factors of
      MS-pathology are highly interdependent causes of grey matter atrophy and
      permanent brain damage. They are associated with intermediate functional effects
      (e.g. in functional MRI) representing a balance between disconnection and (mal)
      adaptive connectivity changes. Therefore, a more comprehensive MRI approach is
      warranted, aiming to link structural changes with functional brain organization.
      To better understand the disconnection syndromes and cognitive decline in MS,
      this paper reviews the associations between MRI metrics and cognitive
      performance, by discussing the interactions between multiple facets of MS
      pathology as determinants of brain damage and how they affect network efficiency.

PMID- 29213427
TI  - Influence of age and education on the Rivermead Behavioral Memory Test (RBMT)
      among healthy elderly.
AB  - : Memory is a cognitive domain extensively evaluated in the neuropsychiatric
      setting. Assessment tools with appropriate norms for age and educational level
      are necessary for the proper interpretation of results. Objective: To present
      normative data for older adults stratified by age and education for the Rivermead
      Behavioral Memory Test (RBMT). The effect of age and education on the total and
      sub-test scores was also analyzed. Methods: A cross-sectional study involving a
      sample of 233 healthy elderly from a third-age group in Porto Alegre with an
      average age of 70 (SD 7.9) years and 10.7 (SD 4.8) years of education was carried
      out. The RBMT is considered an ecologically valid memory test, since it includes
      tasks similar to everyday situations. The sample was stratified into the
      following age groups: 60-69 years, 70-79 years and > 80 years. The sample was
      also divided into individuals with < 8 years and >= 8 years of education.
      Pearson's Chi-squared test and Spearman correlations were used. Results: The
      elderly participants with low educational level had worse performance on all sub
      tests, except the Pictures, Messages, Belongings and Orientation. Older elderly
      performed worse for total RBMT score and on the Face Recognition, Immediate and
      Delayed Route, Messages and Belongings subtests (p <= 0.005). Conclusion:
      Education and age significantly influenced RBMT scores. Therefore, norms for this
      test should be stratified according to these factors.

PMID- 29213426
TI  - Performance of low-educated elders with depression on Addenbrooke's Cognitive
      Examination-Revised (ace-r) test.
AB  - : Along with cognitive disorders, depression has been a concern for mental health
      services due to its highly debilitating effect on the functioning and quality of
      life of the elderly. However, there is still little understanding of the
      cognitive alterations resulting from depression or of the difficult differential
      diagnosis with mild cognitive impairment (MCI). It is known that performance on
      cognitive tests is strongly influenced by education but few studies have been
      conducted involving low-educated populations. Objective: To evaluate the
      performance of elders with low education and no dementia on Addenbrooke's
      Cognitive Examination-Revised (ACE-R) test and its cognitive domains, and compare
      patients with Current Major Depressive Episode (CMDE) against those without
      depressive symptoms. Methods: A retrospective, cross-sectional analytical study
      was conducted based on medical files of patients treated at the Cerebral Aging
      Clinic of the Hospital Sao Lucas of the PUCRS. The study included 116 individuals
      with low education (< 8 years of education) aged between 60 and 84 (69.6 +/- 6.4)
      years, with MCDE (N = 41) and controls (N = 75). Results: No significant
      difference was observed between control and MCDE groups in median scores on the
      ACE-R, Mini-Mental State Examination, and the five cognitive domains. There was
      also no difference between the groups on separate analyses of results on the
      clock drawing test, the categorical verbal and phonological fluency test, and the
      naming test. Conclusion: The results of this study showed that depressive
      symptoms did not influence scores on the ACE-R tests conducted in elders with low
      education.

PMID- 29213428
TI  - Does previous presentation of verbal fluency tasks affect verb fluency
      performance?
AB  - Background: Performance on the verb fluency (VF) task may be influenced by
      administration procedures and demographic factors of each population. Objective:
      The aim of this study was to verify whether the previous administration of
      semantic and phonemic verbal fluency tasks can influence performance on VF; and
      to analyze the correlation of VF performance with education, age and type of
      errors in Brazilian healthy elderly. Methods: Sixty-two participants were
      subdivided into experimental (semantic and the phonemic fluency tasks were
      administered before the VF) and control groups (VF only). The total score and the
      types of errors on the VF task were determined. Additional information was
      computed for the correlational analysis. Results: VF performance did not differ
      statistically between experimental and control groups, but correlated positively
      with education and negatively with intrusions. Conclusion: The lack of influence
      of other verbal fluency tasks on performance of the VF task in elderly
      individuals allows the use of this order of administration. A strong influence of
      educational level on VF task performance reinforces the need for further studies
      in different populations.

PMID- 29213429
TI  - Knowledge and attitudes towards dementia in a sample of medical residents from a
      university-hospital in Sao Paulo, Brazil.
AB  - : An estimated 61% of the 24.3 million people diagnosed with dementia worldwide
      live in underdeveloped countries, including Brazil, where a public healthcare
      system covers the majority of the population. This care is usually provided by
      General Practitioners (GP) and in Brazil many doctors recently graduated from
      medical school and residents of different medical specialties practice as GPs.
      Objective: The aim of this study was to describe the knowledge and attitudes
      about dementia in a sample of Brazilian medical residents from a university
      hospital in Sao Paulo, Brazil. Methods: A total of 152 Brazilian medical
      residents participated in the study. Participants answered a "Knowledge Quiz"
      (KQ) and "Attitude Quiz" (AQ) about dementia issues, transculturally adapted for
      use in Brazilian physicians. A descriptive analysis of the correct answers on
      knowledge and of the attitude aspects was performed. Results: The medical
      residents showed poor knowledge (<50%) about dementia prevalence and incidence
      and a good knowledge on disease management and diagnosis. Participants tended to
      be optimistic about caring for demented patients. Conclusion: In this study, it
      is likely that the physicians' good knowledge about dementia issues is the reason
      for their optimism dealing with demented patients.

PMID- 29213430
TI  - Risk factors for neurocognitive impairment in HIV-infected patients and
      comparison of different screening tools.
AB  - : HIV-associated neurocognitive disorder (HAND) is relatively frequent among HIV
      infected patients and is often underdiagnosed. Assessment of HAND in daily
      clinical practice is challenging and different tools have been proposed.
      Objective: To evaluate risk factors and compare different screening tools for
      neurocognitive impairment in HIV-infected patients. Methods: HIV-infected
      patients were evaluated using the International HIV-Dementia Scale (IHDS), Mini
      Mental State Examination (MMSE) and a neurocognitive self-perception
      questionnaire recommended by the European AIDS Clinical Society.
      Sociodemographic, clinical and laboratory data were obtained through chart review
      and patient interview. Results: Among the 63 patients included, low performance
      on the IHDS was observed in 54.0% and IHDS score was inversely associated with
      age (OR 0.13; 95%CI [0.02-0.67]). Regarding cognitive self-perception, 63.5% of
      patients reported no impairment on the three domains covered by the
      questionnaire. Among those patients self-reporting no problems, 42.1% had low
      performance on the IHDS. None of the patients scored below the education-adjusted
      cut-off on the MMSE. Conclusion: IHDS scores suggestive of HAND were observed in
      more than half of the patients and lower scores were found among older patients.
      There was low agreement between the different tools, suggesting that the MMSE may
      be inadequate for assessing HAND. The self-assessment questionnaire had low
      sensitivity and might not be useful as a screening tool.

PMID- 29213431
TI  - Cognitive functioning in adolescents with migraine.
AB  - : Although migraine is highly prevalent in children and teenagers, it often goes
      undetected in these patients, resulting in underdiagnosis and inadequate
      treatment. Several studies have investigated cognitive changes in adults with
      migraine. However, there are few studies focusing on children and adolescents.
      Objective: To investigate cognitive performance of adolescents with migraine.
      Methods: Twenty-eight adolescents diagnosed with migraine and twenty-six
      individuals without a history of headache were recruited for the study. All
      participants were evaluated using standardized neuropsychological tests. Results:
      Adolescents with migraine had worse performance on tests evaluating short- and
      long-term verbal memory, attention, executive function, and speed of processing
      information than controls. Conclusion: Cognitive dysfunction is common in
      adolescents with migraine. Since the cognitive deficits found in adolescents with
      migraine are similar to those reported in adults with migraine, cognitive
      impairment seems to persist throughout life.

PMID- 29213432
TI  - Validity and reliability of a "simplified" version of the Taylor Complex Figure
      Test for the assessment of older adults with low formal education.
AB  - Objective: The assessment of visuospatial abilities and memory using tasks such
      as the Taylor Complex Figure Task (TCFT) is biased for older adults with low
      formal education. We devised a "Simplified" version of the TCFT designed to
      assess older adults with low educational background and provide preliminary
      evidence of its psychometric properties. Methods: We evaluated a heterogeneous
      sample of healthy older adults and patients with mild cognitive impairment and
      Alzheimer's disease dementia using the simplified TCFT and other
      neuropsychological measures. Results: Our results suggest that the test copy,
      immediate and delayed recall have high inter-rater agreement and internal
      consistency, significant correlations with other tests of visuospatial abilities,
      memory and intelligence, and also detected significant group differences between
      controls and patients. Conclusion: Our study presents a new measure for assessing
      low-educated elderly with promising evidence of validity and reliability.

PMID- 29213433
TI  - Hippocampus discovery First steps.
AB  - The first steps of the discovery, and the main discoverers, of the hippocampus
      are outlined. Arantius was the first to describe a structure he named
      "hippocampus" or "white silkworm". Despite numerous controversies and alternate
      designations, the term hippocampus has prevailed until this day as the most
      widely used term. Duvernoy provided an illustration of the hippocampus and
      surrounding structures, considered the first by most authors, which appeared more
      than one and a half century after Arantius' description. Some authors have
      identified other drawings and texts which they claim predate Duvernoy's
      depiction, in studies by Vesalius, Varolio, Willis, and Eustachio, albeit
      unconvincingly. Considering the definition of the hippocampal formation as
      comprising the hippocampus proper, dentate gyrus and subiculum, Arantius and
      Duvernoy apparently described the gross anatomy of this complex. The pioneering
      studies of Arantius and Duvernoy revealed a relatively small hidden formation
      that would become one of the most valued brain structures.

PMID- 29213435
TI  - The progress of brazilian neuropsychology: From research to clinical practice.

PMID- 29213434
TI  - Capgras syndrome associated with limbic encephalitis in a patient with diffuse
      large B-cell lymphoma.
AB  - We report the case of a patient with insidious onset and slowly progressive
      cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional
      thoughts typical of delusional misidentification syndromes. Clinical presentation
      along with extensive diagnostic work-up revealed limbic encephalitis secondary to
      diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose
      corticosteroid but no significant improvement was observed. No specific treatment
      for lymphoma was performed because the patient died of septic shock following a
      nosocomial respiratory infection. Delusional misidentification syndromes are an
      unusual and unique form of cognitive impairment in which a patient consistently
      misidentifies persons, places, objects, or events. Capgras syndrome is the most
      common subtype of this disorder, being defined by the recurrent and transient
      belief that someone close has been substituted by an imposter. These entities are
      generally associated with neurodegenerative diseases and psychiatric
      disturbances. Rare reports of associations between misidentification syndromes
      and autoimmune diseases such as multiple sclerosis have been published, but no
      papers address a correlation with limbic encephalitis or lymphoma.

PMID- 29213436
TI  - In the June 2016 issue.

PMID- 29213437
TI  - Towards a Brazilian dementia plan? Lessons to be learned from Europe.
AB  - Dementia is a global socio-medical problem. The steepest increase in prevalence
      occurs in Latin-America and Asia. European governments have implemented dementia
      plans to improve care. We describe common goals of European dementia plans and
      discuss the Brazilian situation. Sixteen European countries have governmental
      dementia plans, another four are set to launch them. These plans have some common
      goals: to raise general awareness on dementia and reduce stigma, to establish
      more diagnostic centers and increase the number of people with correct diagnoses,
      to provide integrated care that improves quality of care and quality of life, and
      to promote educational programs for family and professional carers. European
      dementia plans have contributed toward raising awareness about dementia. More
      reference centers for diagnostic evaluations have been established and successful
      educational programs have been run. Integrated care is still a challenge in most
      countries. Brazil needs a plan. Facilitators and barriers for implementation
      should be identified by studying the European plans.

PMID- 29213439
TI  - Heterogeneity in semantic priming effect with a lexical decision task in patients
      after left hemisphere stroke.
AB  - Investigations on the semantic priming effect (SPE) in patients after left
      hemisphere (LH) lesions have shown disparities that may be explained by the
      variability in performance found among patients. The aim of the present study was
      to verify the existence of subgroups of patients after LH stroke by searching for
      dissociations between performance on the lexical decision task based on the
      semantic priming paradigm and performance on direct memory, semantic association
      and language tasks. All 17 patients with LH lesions after stroke (ten non-fluent
      aphasics and seven non aphasics) were analyzed individually. Results indicated
      the presence of three groups of patients according to SPE: one exhibiting SPE at
      both stimulus onset asynchronies (SOAs), one with SPE only at long SOA, and
      another, larger group with no SPE.

PMID- 29213438
TI  - Imaging Alzheimer's disease pathophysiology with PET.
AB  - Alzheimer's disease (AD) has been reconceptualised as a dynamic
      pathophysiological process characterized by preclinical, mild cognitive
      impairment (MCI), and dementia stages. Positron emission tomography (PET)
      associated with various molecular imaging agents reveals numerous aspects of
      dementia pathophysiology, such as brain amyloidosis, tau accumulation,
      neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia
      patients. In the context of a growing shift toward presymptomatic early diagnosis
      and disease-modifying interventions, PET molecular imaging agents provide an
      unprecedented means of quantifying the AD pathophysiological process, monitoring
      disease progression, ascertaining whether therapies engage their respective brain
      molecular targets, as well as quantifying pharmacological responses. In the
      present study, we highlight the most important contributions of PET in describing
      brain molecular abnormalities in AD.

PMID- 29213440
TI  - The Learning Curve in neurofeedback of Peter Van Deusen: A review article.
AB  - The Learning Curve (TLC) in neurofeedback concept emerged after Peter Van Deusen
      compiled the results of articles on the expected electrical activity of the
      brain. This concept was subsequently tested on patients at four clinics in
      Atlanta between 1994 and 2001. The aim of this paper was to report the historical
      aspects of TLC. Articles published on the electronic databases MEDLINE/PubMed and
      Web of Science were reviewed. During patient evaluation, TLC investigates
      categories called disconnected, hot temporal lobes, reversal of alpha and beta
      waves, blocking, locking, and filtering or processing. This enables
      neuroscientists to use their training designs and, by means of behavioral
      psychology, to work on neuroregulation, as self-regulation for patients. TLC
      shows the relationships between electrical, mental and behavioral activity in
      patients. It also identifies details of patterns that can assist physicians in
      their choice of treatment.

PMID- 29213441
TI  - Voxel-based morphometry in Alzheimers disease and mild cognitive impairment:
      Systematic review of studies addressing the frontal lobe.
AB  - : Voxel-based morphometry (VBM) is a useful approach for investigating
      neurostructural brain changes in dementia. We systematically reviewed VBM studies
      of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically
      focusing on grey matter (GM) atrophy in the frontal lobe. Methods: Two searches
      were performed on the Pubmed database. A set of exclusion criteria was applied to
      ensure the selection of only VBM studies that directly investigated GM volume
      abnormalities in AD and/or MCI patients compared to cognitively normal controls.
      Results: From a total of 46 selected articles, 35 VBM studies reported GM volume
      reductions in the frontal lobe. The frontal subregions, where most of the volume
      reductions were reported, included the inferior, superior and middle frontal
      gyri, as well as the anterior cingulate gyrus. We also found studies in which
      reduced frontal GM was detected in MCI patients who converted to AD. In a
      minority of studies, correlations between frontal GM volumes and behavioural
      changes or cognitive deficits in AD patients were investigated, with variable
      findings. Conclusion: Results of VBM studies indicate that the frontal lobe
      should be regarded as an important brain area when investigating GM volume
      deficits in association with AD. Frontal GM loss might not be a feature specific
      to late AD only. Future VBM studies involving large AD samples are warranted to
      further investigate correlations between frontal volume deficits and both
      cognitive impairment and neuropsychiatric symptoms.

PMID- 29213442
TI  - Metamemory and aging: Psychometric properties of the Brazilian version of the
      Multifactorial Memory Questionnaire for elderly.
AB  - : Metamemory measures provide subjective memory information and are relevant to
      investigate memory ability in aging. However, there is a lack of metamemory
      instruments available in Brazil. Objective: The aim of this study was to examine
      the psychometric properties of the Brazilian version of the Multifactorial Memory
      Questionnaire (MMQ), which evaluates different dimensions of subjective memory
      functioning, such as Feelings, Abilities and Strategies used in everyday life.
      Methods: The MMQ was translated into Portuguese and administered to 30 Brazilian
      elderly subjects. The participants underwent cognitive tests, mood scales and
      metamemory instruments. Results: Analyses revealed good internal consistency
      (Cronbach's a coefficient ranged from 0.75 to 0.89) and test-retest validity for
      each MMQ dimensions (positive correlations between two applications ranged from
      0.75 to 0.8). Convergent validity evidence for the MMQ was confirmed by
      significant positive correlations (0.47 to 0.68) with dimensions of the
      Metamemory in Adulthood scale (MIA) (i.e., the Ability, Control, Self-efficacy
      and Strategy dimensions). Discriminant validity revealed no associations between
      the MMQ and cognitive performance, suggesting a weak metamemory-objective memory
      correspondence. Moreover, there was a negative correlation between MMQ-Ability
      subscale scores and mood symptoms (-0.63 for anxious symptoms, and -0.54 for
      depressive symptoms); and the Brazilian MMQ was comparable with MMQ translations
      to other languages. Conclusion: The Brazilian MMQ exhibits good psychometric
      properties and appears promising for clinical and research purposes. Additional
      studies are needed to further examine the psychometric properties of the
      Brazilian MMQ in a larger sample.

PMID- 29213443
TI  - Neuropsychological benefits of a narrative cognitive training program for people
      living with dementia: A pilot study.
AB  - : Many areas in the cortex are active during reading of narrative material, and
      these activations in the brain produce significant changes in connectivity.
      Following previous results showing cognitive benefits in memory domains of a
      narrative training program in nursing home patients living with dementia, the aim
      of the present study was to perform a more in depth investigation of the effects
      of this training on memory domains and other cognitive areas. Methods: An
      experimental group of eight patients underwent auditory narrative training of 60
      hours. At the beginning and end of the training, subjects were tested with a
      neuropsychological battery to quantify any improvements in individual
      performance. Results: The results showed a statistically significant improvement
      in the list learning task (immediate memory) and list learning recognition for
      single tasks, and a statistically significant improvement in overall cognitive
      area scores for immediate and delayed memory. Conclusion: Results replicate and
      expand our previous findings, indicating that this type of intervention can
      increase performance on memory-related tests.

PMID- 29213444
TI  - Methylphenidate as a cognitive enhancer in healthy young people.
AB  - : The so-called cognitive enhancers have been widely and increasingly used by
      healthy individuals who seek improvements in cognitive performance despite having
      no pathologies. One drug used for this purpose is methylphenidate, a first-line
      drug for the treatment of attention deficit hyperactivity disorder (ADHD).
      Objective: The aim of the present study was to test the effect of acute
      administration of varying doses of methylphenidate (10 mg, 20 mg, 40 mg and
      placebo) on a wide range of cognitive functions in healthy young people. Methods:
      A total of 36 young university students and graduates participated in the study.
      The participants underwent tests of attention and of episodic, and working
      memory. Results: No differences in performance were observed on any of the tests.
      There was a dose-dependent (40 mg > placebo) effect on self-reported wellbeing.
      Conclusions: According to the recent literature, psychostimulant medications,
      such as methylphenidate, improve performance when cognitive processes are below
      an optimal level, which was not the case for the subjects of the present study.
      We suggest the impression that methylphenidate enhances cognitive performance in
      healthy young people, justifying its use, may be due to improvements in
      subjective wellbeing promoted by the drug.

PMID- 29213445
TI  - Effect of caregiver characteristics on dementia management strategies.
AB  - : Caregiving has an important influence on the prognosis of dementia,
      particularly regarding the management strategy implemented. Therefore, evaluating
      which characteristics of caregivers can influence the choice of a particular
      strategy for managing dementia is needed. Objective: To evaluate the association
      between characteristics of caregivers and their management strategies as applied
      to patients with dementia. Methods: A cross-sectional study involving 45
      professional caregivers from two nursing homes in Porto Alegre, Brazil, was
      conducted. Age, gender, education, years as a caregiver, income, burden,
      depressive and anxiety symptoms and dementia management strategies were evaluated
      for all participants. Pearson's or Spearman's correlation tests were applied
      according to the variable distribution (parametric or non-parametric). Bivariate
      correlation analysis was applied. P<0.05 was considered statistically
      significant. Results: There was a significant and moderate positive correlation
      between burden measured by the Zarit Burden Interview and criticism measured by
      the Dementia Management Strategies Scale (Spearman's rho = 0.555, p < 0.001). No
      other correlations were observed. Conclusion: Among the caregiver characteristics
      that directly affect the approach to managing dementia, high caregiver burden was
      found to be associated with high criticism, an authoritative way of managing
      dementia. This exploratory study indicated that a possible way of decreasing
      negative dementia management is to reduce caregiver burden.

PMID- 29213446
TI  - Psychosis and concurrent impulse control disorder in Parkinson's disease: A
      review based on a case report.
AB  - Psychosis, impulse control disorders (e.g., pathological gambling and
      hypersexuality) and repetitive behaviors such as punding are known psychiatric
      complications of Parkinson's disease (PD). Impulsive, compulsive and repetitive
      behaviors are strongly associated with dopamine-replacement therapy. We present
      the case of a 58-year-old man with PD and a myriad of psychiatric symptoms.
      Concurrent psychosis, punding and pathological gambling developed more than six
      years after the introduction of pramipexole and ceased shortly after the addition
      of quetiapine and discontinuation of pramipexole. This report emphasizes the
      importance of monitoring for a wide array of psychiatric symptoms in patients on
      dopamine replacement therapy.

PMID- 29213447
TI  - Memory training and benefits for quality of life in the elderly: A case report.
AB  - Studies emphasize the training of cognitive functions to decrease losses in the
      population. Memory training associated with neurotracker was performed by an 80
      year-old man with memory complaints. A battery for measuring memory, quality of
      life and stress was initially applied and showed low scores. The patient
      underwent a program for stimulating memory and attention comprising 32 sessions
      (2 weekly sessions of 90 minutes each). The post-test follow-up showed
      improvements in the process of storage and retrieval of episodic and working
      memory, greater use of strategies, faster information processing speed, as well
      as reduction in complaints and positive impact on quality of life. The results
      suggest that the use of Neurotracker for training cognitive processes is valid
      for cognitive rehabilitation programs to promote improvements in quality of life
      in the elderly.

PMID- 29213448
TI  - Adjuvant transcranial direct current stimulation for treating Alzheimer's
      disease: A case study.
AB  - We report the case of a 73-year-old male patient with Alzheimer's disease who
      underwent 10-daily transcranial direct current stimulation (tDCS) sessions. tDCS
      was applied over the left dorsolateral prefrontal cortex as an adjuvant to the
      traditional treatment that the patient was receiving, which consisted of
      anticholinergic medication and cognitive training. The data were qualitatively
      analyzed and are presented in an analytic and structured form. The effects on
      cognitive performance were evaluated using the Alzheimer's Disease Assessment
      Scale-cognitive subscale as the primary outcome. Secondary outcomes were assessed
      with a set of tests consisting of the Neuropsychiatric Inventory, the Blessed
      Dementia Scale and the Disability Assessment for Dementia. The data obtained
      revealed that the application of tDCS had a stabilizing effect on overall patient
      cognitive function and led to improved performance on all the secondary outcome
      tests. These preliminary results indicate that tDCS is a potential adjuvant
      therapeutic tool for cognitive rehabilitation in Alzheimer's disease .

PMID- 29213449
TI  - Neurodegeneration with brain iron accumulation: A case report.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive
      disorder caused by mutation in the PANK2 gene. It is characterized by abnormal
      brain iron accumulation, mainly in the globus pallidus. PKAN is included in a
      group of disorders known as neurodegeneration with brain iron accumulation
      (NBIA). We report a case of atypical PKAN with its most characteristic
      presentation, exhibiting marked psychiatric symptoms, speech disorder and focal
      dystonia. Brain MRI has great diagnostic importance in this group of disorders
      and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed
      the diagnosis.

PMID- 29213450
TI  - Progressive multifocal leukoencephalopathy in non-HIV patient.

PMID- 29213451
TI  - In the September 2016 issue.

PMID- 29213452
TI  - Subjective cognitive decline: The first clinical manifestation of Alzheimer's
      disease?
AB  - Background: Mild cognitive impairment is considered as the first clinical
      manifestation of Alzheimer's disease (AD), when the individual exhibits below
      performance on standardized neuropsychological tests. However, some subjects
      before having a lower performance on cognitive assessments already have a
      subjective memory complaint. Objective: A review about subjective cognitive
      decline, the association with AD biomarkers and risk of conversion to dementia.
      Methods: We performed a comprehensive non-systematic review on PubMed. The
      keywords used in the search were terms related to subjective cognitive decline.
      Results: Subjective cognitive decline is characterized by self-experience of
      deterioration in cognitive performance not detected objectively through formal
      neuropsychological testing. However, various terms and definitions have been used
      in the literature and the lack of a widely accepted concept hampers comparison of
      studies. Epidemiological data have shown that individuals with subjective
      cognitive decline are at increased risk of progression to AD dementia. In
      addition, there is evidence that this group has a higher prevalence of positive
      biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is
      not the only cause of subjective cognitive decline and various other conditions
      can be associated with subjective memory complaints, such as psychiatric
      disorders or normal aging. The features suggestive of a neurodegenerative
      disorder are: onset of decline within the last five years, age at onset above 60
      years, associated concerns about decline and confirmation by an informant.
      Conclusion: These findings support the idea that subjective cognitive complaints
      may be an early clinical marker that precedes mild cognitive impairment due to
      Alzheimer's disease.

PMID- 29213453
TI  - Effects of cognitive stimulation on neuropsychiatric symptoms in elderly with
      Alzheimer's disease: A systematic review.
AB  - Introduction: Neuropsychiatric symptoms are frequent in Alzheimer's disease and
      negatively affect patient quality of life. Objective: To assess the effectiveness
      of cognitive stimulation on neuropsychiatric symptoms in elderly patients with
      Alzheimer's disease. Methods: The included articles were reviewed between
      December 2015 and June 2016, and the inclusion criteria were: (1) studies
      involving older adults diagnosed with Alzheimer's disease; (2) studies published
      in English, Spanish or Portuguese; (3) studies that determined the effect of
      cognitive stimulation on neuropsychiatric symptoms in elderly patients with
      Alzheimer's disease; (4) controlled trials. Results: Out of the total 722, 9
      articles matched the inclusion criteria. Depression, apathy and anxiety were the
      most frequent symptoms. Conclusion: Studies reported significant results post
      treatment, suggesting cognitive stimulation can be effective for these
      neuropsychiatric symptoms, thus improving the quality of life of Alzheimer's
      disease patients and their caregivers.

PMID- 29213455
TI  - Association of education with occurrence of delirium in patients from an
      emergency department.
AB  - Background: Delirium is a neuropsychiatric syndrome with multiple etiological
      factors. Evaluation of delirium in different settings, especially the Emergency
      Department (ED) pertaining to different regions of the world with patients from
      different cultural and educational backgrounds is needed. Objective: To determine
      the prevalence of delirium and its association with education in an ED in Brazil
      during a 6-month period. Methods: Patients aged >18 years were randomly selected
      from ED admissions. The instruments Confusion Assessment. Method: (CAM) scale,
      Mini-Mental State Examination (MMSE), Wechsler Logical Memory (WLM) and Charlson
      comorbidity score were applied to evaluate delirium, cognitive status, and
      comorbidities. Results: The prevalence of delirium was10.7%. Delirium patients
      had significantly lower education, MMSE and WLM (immediate and delayed) scores,
      with 97.4% presenting episodic memory impairment. Patients with delirium had more
      history of neurological disorders. Three logistic regression models evaluating
      the association of variables with delirium were developed. Age and MMSE were
      retained in the first model, WLM scores in the second, and education in the
      third. Conclusion: To the best of our knowledge, this is the first study
      estimating the prevalence of delirium in a Brazilian ED. Lower education was
      associated with the occurrence of delirium.

PMID- 29213454
TI  - Sleep and executive functions in older adults: A systematic review.
AB  - Introduction: A recent increase in studies suggests a role of age-related sleep
      changes in executive functions (EF). However, this relationship remains unclear
      and mixed results have emerged. Objective: To investigate how age-related sleep
      changes may play an important role in the extent to which healthy older adults
      exhibit decline in EF. Methods: A systematic strategy was employed to identify
      the available literature on age-related sleep changes and EF. Results: Of the 465
      studies identified, 26 were included. Results: suggest that multiple sleep
      parameters differ in the way they benefit or impair EF. Parameters such as
      greater wake after sleep onset and lower sleep efficiency, in addition to
      circadian fragmentation of sleep, showed more consistent results and are
      potentially correlated with worsening in EF measures. However, other results seem
      inconclusive. Conclusion: These findings were discussed based on the prefrontal
      circuitry vulnerability model, in which sleep has been identified as a beneficial
      factor for prefrontal cortex functioning and hence for EF, which relies mostly on
      this brain area and its related networks.

PMID- 29213456
TI  - Delayed recall memory impairment in patients with Parkinson's disease.
AB  - : Age is one of the risk factors for dementia in patients with Parkinson's
      disease (PDD). Distinct cognitive syndromes of Parkinson's disease (PD) have been
      identified in previous studies. Questions about the role of such cognitive
      disorders in PD outcomes, especially memory dysfunction, in patients with PD
      remain unanswered. Objective: To establish possible correlations between delayed
      recall memory (episodic memory), age, and other demographic variables in patients
      with PD. Methods: A two-stage protocol was applied. Patients with delayed recall
      memory compromise, selected based on a brief battery of tests (BBRC-Edu), were
      classified as dementia cases and submitted to the Mattis Dementia Rating Scale
      (MDRS). Data from patients with memory disturbances were compared against
      individuals without episodic memory impairment, and correlated with age and
      demographic variables. Results: Except for identification and naming, all
      subtests in the screening battery showed a significant difference (p<=0.0001)
      between the memory-compromised group (case) and the group without memory
      impairment (no case). The results also correlated negatively with age (p<=0.0001)
      and positively with level of education (p=0.0874) in patients with PD.
      Conclusion: The analysis showed a significant relationship between age and
      dementia characterized by impaired episodic memory. The findings support reports
      of a wide spectrum of neuropsychological performance impairment in PD with age,
      particularly dementia associated with memory deterioration. No correlations
      between disease duration and cognitive dysfunction were evident.

PMID- 29213457
TI  - Sensorimotor speech disorders in Parkinson's disease: Programming and execution
      deficits.
AB  - Introduction: Dysfunction in the basal ganglia circuits is a determining factor
      in the physiopathology of the classic signs of Parkinson's disease (PD) and
      hypokinetic dysarthria is commonly related to PD. Regarding speech disorders
      associated with PD, the latest four-level framework of speech complicates the
      traditional view of dysarthria as a motor execution disorder. Based on findings
      that dysfunctions in basal ganglia can cause speech disorders, and on the premise
      that the speech deficits seen in PD are not related to an execution motor
      disorder alone but also to a disorder at the motor programming level, the main
      objective of this study was to investigate the presence of sensorimotor disorders
      of programming (besides the execution disorders previously described) in PD
      patients. Methods: A cross-sectional study was conducted in a sample of 60 adults
      matched for gender, age and education: 30 adult patients diagnosed with
      idiopathic PD (PDG) and 30 healthy adults (CG). All types of articulation errors
      were reanalyzed to investigate the nature of these errors. Interjections,
      hesitations and repetitions of words or sentences (during discourse) were
      considered typical disfluencies; blocking, episodes of palilalia (words or
      syllables) were analyzed as atypical disfluencies. We analysed features including
      successive self-initiated trial, phoneme distortions, self-correction, repetition
      of sounds and syllables, prolonged movement transitions, additions or omissions
      of sounds and syllables, in order to identify programming and/or execution
      failures. Orofacial agility was also investigated. Results: The PDG had worse
      performance on all sensorimotor speech tasks. All PD patients had hypokinetic
      dysarthria. Conclusion: The clinical characteristics found suggest both execution
      and programming sensorimotor speech disorders in PD patients.

PMID- 29213458
TI  - Validation of the Argentine version of the Memory Binding Test (MBT) for Early
      Detection of Mild Cognitive Impairment.
AB  - Background: "Forgetfulness" is frequent in normal aging and characteristic of the
      early stages of dementia syndromes. The episodic memory test is central for
      detecting amnestic mild cognitive impairment (MCI). The Memory Binding Test (MBT)
      is a simple, easy and brief memory test to detect the early stage of episodic
      memory impairment. Objective: To validate the Argentine version of the MBT in a
      Latin American population and to estimate the diagnostic accuracy as a tool for
      early detection of MCI. Methods: 88 subjects (46 healthy controls and 42 patients
      with amnestic MCI) matched for age and educational level were evaluated by an
      extensive neuropsychological battery and the memory binding test. Results: A
      significantly better performance was detected in the control group; all MBT
      scales were predictive of MCI diagnosis (p<.01). The MBT showed high sensitivity
      (69%) and high specificity (88%), with a PPV of 93% and a NPV of 55% for
      associative paired recall. A statistically significant difference (c2=14,164,
      p<.001) was obtained when comparing the area under the curve (AUC) of the MBT
      (0.88) and the MMSE (0.70). Conclusion: The Argentine version of the MBT
      correlated significantly with the MMSE and the memory battery and is a useful
      tool in the detection of MCI. The operating characteristics of the MBT are well
      suited, surpassing other tests commonly used for detecting MCI.

PMID- 29213459
TI  - The Clock Drawing Test: Performance differences between the free-drawn and
      incomplete-copy versions in patients with MCI and dementia.
AB  - Background: The Clock Drawing Test (CDT) is a brief cognitive screening tool for
      dementia. Several different presentation formats and scoring methods for the CDT
      are available in the literature. Objective: In this study we aimed to compare
      performance on the free-drawn and "incomplete-copy" versions of the CDT using the
      same short scoring method in Mild Cognitive Impairment (MCI) and dementia
      patients, and healthy elderly participants. Methods: 90 participants (controlled
      for age, sex and education) subdivided into control group (n=20), MCI group
      (n=30) and dementia group (n=40) (Alzheimer's disease - AD=20; Vascular Dementia 
      VD=20) were recruited for this study. The participants performed the two CDT
      versions at different times and a blinded neuropsychologist scored the CDTs using
      the same scoring system. Results: The scores on the free-drawn version were
      significantly lower than the incomplete-copy version for all groups. The dementia
      group had significantly lower scores on the incomplete-copy version of the CDT
      than the control group. MCI patients did not differ significantly from the
      dementia or control groups. Performance on the free-drawn copy differed
      significantly among all groups. Conclusion: The free-drawn CDT version is more
      cognitively demanding and sensitive for detecting mild/early cognitive
      impairment. Further evaluation of the diagnostic value (accuracy) of the free
      drawn CDT in Brazilian MCI patients is needed.

PMID- 29213460
TI  - The influence of age, gender and education on the performance of healthy
      individuals on a battery for assessing limb apraxia.
AB  - Introduction: Apraxia is defined as a disorder of learned skilled movements, in
      the absence of elementary motor or sensory deficits and general cognitive
      impairment, such as inattention to commands, object-recognition deficits or poor
      oral comprehension. Limb apraxia has long been a challenge for clinical
      assessment and understanding and covers a wide spectrum of disorders, all
      involving motor cognition and the inability to perform previously learned
      actions. Demographic variables such as gender, age, and education can influence
      the performance of individuals on different neuropsychological tests. Objective:
      The present study aimed to evaluate the performance of healthy subjects on a limb
      apraxia battery and to determine the influence of gender, age, and education on
      the praxis skills assessed. Methods: Forty-four subjects underwent a limb apraxia
      battery, which was composed of numerous subtests for assessing both the semantic
      aspects of gestural production as well as motor performance itself. The tasks
      encompassed lexical-semantic aspects related to gestural production and motor
      activity in response to verbal commands and imitation. Results: We observed no
      gender effects on any of the subtests. Only the subtest involving visual
      recognition of transitive gestures showed a correlation between performance and
      age. However, we observed that education level influenced subject performance for
      all sub tests involving motor actions, and for most of these, moderate
      correlations were observed between education level and performance of the praxis
      tasks. Conclusion: We conclude that the education level of participants can have
      an important influence on the outcome of limb apraxia tests.

PMID- 29213462
TI  - Arteriovenous malformation and dementia: A case report.
AB  - Arteriovenous malformation (AVM) is a congenital lesion commonly associated with
      intracranial hemorrhage. We describe a woman with an AVM (Spetzler-Martin grade
      V) and presenile progressive dementia. The association between AVM and cognition
      is discussed.

PMID- 29213461
TI  - Mother and daughter with adolescent-onset severe frontal lobe dysfunction and
      epilepsy.
AB  - Familial cases of early-onset prominent frontal lobe dysfunction associated with
      epilepsy have not been reported to date. We report a mother and her only daughter
      with incapacitating behavioral manifestations of frontal lobe dysfunction and
      epilepsy of variable severity. The possibility of a hitherto undescribed genetic
      condition is discussed.

PMID- 29213463
TI  - Brazilian National Anthem presenting as musical hallucination: A case report with
      9-year follow-up.
AB  - Musical hallucination is a type of complex auditory hallucination. Possible
      etiologies are deafness, psychiatric disorders such as schizophrenia, major
      depression, use of medication and stress, besides neurologic diseases including
      epilepsy, stroke and cancer. Uncommon etiologies encompass infectious diseases,
      metabolic disorders, and sensory deprivation. Although musical hallucinations
      have a major impact on patients' lives, they have been undervalued and
      understudied in the literature. We report a case of a 79-year-old woman with
      musical hallucination (hearing a sung National anthem) without cognitive
      impairment or hearing loss. The patient had preserved insight of her complaint
      and responded well to neuroleptics.

PMID- 29213464
TI  - All that glitters is not gold: When motor and vocal tics in a child do not match
      Tourette syndrome: A case report.
AB  - The atypical form of Pantothenate Kinase-Associated Neurodegeneration (PKAN)
      tends to present at around the age of 14 years, has a heterogeneous presentation
      with extrapyramidal symptoms, and approximately one third of patients exhibit
      psychiatric problems. This paper reports the case of a patient with apparent
      typical symptoms of Tourette syndrome. However, the severity and poor response to
      treatment led to further investigation and the diagnosis of PKAN as a secondary
      cause of Tourettism was reached.

PMID- 29213465
TI  - Magendie and Luschka: Holes in the 4th ventricle.
AB  - Cerebrospinal fluid (CSF) is a complex liquid formed mainly by the choroid
      plexuses. After filling the ventricular system where it circulates, CSF flows out
      to the subarachnoid spaces through openings in the 4th ventricle. Following
      numerous studies on CSF pathways, these openings were first discovered in the
      19th century by two notable researchers, Francois Magendie and Hubert von
      Luschka, who described the median and lateral openings subsequently named after
      them. Even after the studies of Axel Key and Gustav Magnus Retzius confirming
      these openings, their existence was questioned by many anatomists, yet
      acknowledged by others. Finally gaining the acceptance of all, recognition of the
      holes endures to the present day. Interest in these openings may be attributed to
      the several congenital or acquired pathological conditions that may affect them,
      usually associated with hydrocephalus. We report some historical aspects of these
      apertures and their discoverers.

PMID- 29213466
TI  - Cognitive dysfunction and dementia in movement disorders.

PMID- 29213467
TI  - Revisiting the neuropsychiatry of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      classified under the choreas. Besides motor symptoms, HD is marked by cognitive
      and behavioral symptoms, impacting patients' functional capacity. The progression
      of cognitive impairment and neuropsychiatric symptoms occur in parallel with
      neurodegeneration. The nature of these symptoms is very dynamic, and the major
      clinical challenges include executive dysfunction, apathy, depression and
      irritability. Herein, we provide a focused updated review on the cognitive and
      psychiatric features of HD.

PMID- 29213468
TI  - Corticobasal syndrome: A diagnostic conundrum.
AB  - Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome of great
      interest to movement disorder specialists and behavioral neurologists. Although
      originally considered a primary motor disorder, it is now also recognized as a
      cognitive disorder, usually presenting cognitive deficits before the onset of
      motor symptoms. The term CBS denotes the clinical phenotype and is associated
      with a heterogeneous spectrum of pathologies. Given that disease-modifying agents
      are targeting the pathologic process, new diagnostic methods and biomarkers are
      being developed to predict the underlying pathology. The heterogeneity of this
      syndrome in terms of clinical, radiological, neuropsychological and pathological
      aspects poses the main challenge for evaluation.

PMID- 29213469
TI  - Cognitive dysfunction in hereditary spastic paraplegias and other motor neuron
      disorders.
AB  - Hereditary spastic paraplegia (HSP) is a diverse group of single-gene disorders
      that share the predominant clinical feature of progressive lower limb spasticity
      and weakness. More than 70 different genetic subtypes have been described and all
      modes of inheritance are possible. Intellectual dysfunction in HSP is frequent in
      recessive forms but rare in dominant families. It may manifest by either mental
      retardation and/or cognitive decline. The latter may be subtle, restricted to
      executive dysfunction or may evolve to severe dementia. The cognitive profile is
      thought to depend largely on the genetic subtype of HSP, although wide phenotypic
      variability within the same genetic subtype and also within the same family can
      be found.

PMID- 29213470
TI  - Gait, posture and cognition in Parkinson's disease.
AB  - Gait disorders and postural instability are the leading causes of falls and
      disability in Parkinson's disease (PD). Cognition plays an important role in
      postural control and may interfere with gait and posture assessment and
      treatment. It is important to recognize gait, posture and balance dysfunctions by
      choosing proper assessment tools for PD. Patients at higher risk of falling must
      be referred for rehabilitation as early as possible, because antiparkinsonian
      drugs and surgery do not improve gait and posture in PD.

PMID- 29213472
TI  - Neuropsychological profile of Parkinson's disease patients selected for deep
      brain stimulation surgery.
AB  - Background: Parkinson's disease (PD) shows symptoms involving motor and non-motor
      complications, including cognitive and behavioral changes, such changes might to
      contraindicate deep brain stimulation surgery (DBS). Objective: The aim of study
      was to investigate the neuropsychological profile of patients with PD in a
      waiting list for DBS. Methods: The neuropsychological evaluation was held in 30
      patients of the ISCMPA Movement Disorders Clinic, with surgical indication based
      on the criteria of the responsible neurologists, in the period of 12 months.
      Instruments used: MMSE, FAB, MoCA, BDI, Semantic Verbal Fluency, PDQ-39, PDSS;
      and the UPDRS and Hoehn-Yahr scale. Results: The patients were mostly male
      (66.7%) with a mean age of 59.37 (SD 10.60) and disease duration 9.33 (SD 4.08).
      There was cognitive impairment in 56.7% of patients by FAB and 76.7% by MoCA.
      Conclusion: Even in the earliest stages of the disease, there is the incidence of
      non-motor symptoms, especially in those subjects who had an early onset of the
      disease.

PMID- 29213471
TI  - Cell-based technologies for Huntington's disease.
AB  - Huntington's disease (HD) is a fatal genetic disorder, which causes the
      progressive breakdown of neurons in the human brain. HD deteriorates human
      physical and mental abilities over time and has no cure. Stem cell-based
      technologies are promising novel treatments, and in HD, they aim to replace lost
      neurons and/or to prevent neural cell death. Herein we discuss the use of human
      fetal tissue (hFT), neural stem cells (NSCs) of hFT origin or embryonic stem
      cells (ESCs) and induced pluripotent stem cells (IPSCs), in clinical and pre
      clinical studies. The in vivo use of mesenchymal stem cells (MSCs), which are
      derived from non-neural tissues, will also be discussed. All these studies prove
      the potential of stem cells for transplantation therapy in HD, demonstrating cell
      grafting and the ability to differentiate into mature neurons, resulting in
      behavioral improvements. We claim that there are still many problems to overcome
      before these technologies become available for HD patient treatment, such as: a)
      safety regarding the use of NSCs and pluripotent stem cells, which are
      potentially teratogenic;b) safety regarding the transplantation procedure itself,
      which represents a risk and needs to be better studied; and finallyc) technical
      and ethical issues regarding cells of fetal and embryonic origin.

PMID- 29213473
TI  - The impact of cognitive performance on quality of life in individuals with
      Parkinson's disease.
AB  - Background: Evidence points to the occurrence of cognitive impairment in all
      stages of PD, constituting a frequent and debilitating symptom, due to high
      impact on quality of life and mortality of patients. Objective: To correlate
      cognitive performance with quality of life in PD. Methods: The sample was drawn
      from a Movement Disorders Clinic of a reference hospital in Porto Alegre.
      Inclusion criteria were: PD diagnosis, according to the United Kingdom
      Parkinson's Disease Society Brain Bank criteria for idiopathic PD (Hughes et al.
      1992) and patient consent to participate. Patients with other neurological
      pathologies and those submitted to deep brain stimulation were excluded. The
      evaluation consisted of a cognitive testing battery (composed of eight tests for
      assessing cognitive performance), and a questionnaire on quality of life (PDQ-39)
      and depression (BDI). Results: The sample comprised 85 individuals with PD, with
      a mean age of 62.9 years (+/-10.7), mean disease duration of 10.4 years (+/-5.7),
      and mean educational level of four years (+/-4.3). There was a significant
      relationship between total score on the PDQ and all cognitive tests, showing that
      poor cognitive performance was correlated with poor quality of life. Moreover, a
      significant correlation was observed between cognitive tests and depression, H&Y,
      education level, and age. Conclusion: It may be concluded that the individuals
      with PD in this sample showed a correlation between poorer quality of life and
      worse cognitive performance. Poor performance was also correlated with more
      advanced stage, older age, low level of education and depression.

PMID- 29213474
TI  - Cognitive impairment in Spinocerebellar ataxia type 10.
AB  - Background: Cognitive and psychiatric dysfunction has been described in several
      neurodegenerative diseases but has not been systematically evaluated in
      spinocerebellar ataxia type 10 (SCA10). Objective: The aim of the present study
      was to investigate the core cognitive features in a large cohort of Brazilian
      patients with SCA10, comparing the results against a healthy control group.
      Methods: Twenty-eight SCA10 and 28 healthy subjects were prospectively assessed
      regarding cognitive function and psychiatric disorders at the Movement Disorders
      Unit of the Federal University of Parana between February 2012 and October 2014.
      Results: The SCA10 group had worse depression scores, as well as cognitive
      performance, when compared to healthy individuals. Conclusion: Our study showed
      mild cognitive and mood dysfunctions in patients with SCA10, consistent with the
      symptoms reported in the Cerebellar Cognitive Affective Syndrome described by
      Schmahmann JD in 1998. The description of these findings is an important clinical
      phenomenon that may guide physicians in specific disease management and improve
      quality of life of these patients.

PMID- 29213475
TI  - Cluster analysis of cognitive performance in a sample of patients with
      Parkinson's disease.
AB  - Background: Cognitive impairment is a common feature of Parkinson's disease (PD).
      The diagnoses of mild cognitive impairment (MCI) in patients with PD implies an
      increased risk for later development of dementia, however, it is unclear whether
      a specific type of cognitive loss confers increased risk for faster cognitive
      decline. Objective: Determine whether it was possible to identify distinct
      cognitive phenotypes in a sample of patients with PD. Methods: A cross-sectional
      evaluation of 100 patients with PD recruited from a movement disorders clinic was
      conducted. The patients were evaluated using the simplified motor score of the
      UPDRS, the Hoehn and Yahr, Schwab and England, Geriatric Depression Scale,
      Pfeffer Functional Activities Questionnaire, Clinical Dementia Rating Scale, Mini
      Mental State Examination, clock drawing test, digit span, word list battery of
      CERAD, Frontal Assessment Battery and verbal fluency test. We classified the
      patients as having normal cognition (PDNC), MCI (PDMCI) or dementia (PDD). Data
      were analyzed using the chi-square test, non-parametric statistics and cluster
      analysis. Results: There were 40 patients with PDD, 39 with PDMCI and 21 with
      PDNC. Patients with PDD were older, had longer disease duration, lower education
      and lower MMSE scores. Cluster analysis showed 3 general distinct cognitive
      profiles that represented a continuum from mild to severe impairment of
      cognition, without distinguishing specific cognitive profiles. Conclusion:
      Cognitive impairment in PD occurs progressively and heterogeneously in most
      patients. It is unclear whether the definition of the initial phenotype of
      cognitive loss can be used to establish the cognitive prognosis of patients.

PMID- 29213476
TI  - Which factors are associated with global cognitive impairment in Wilson's
      disease?
AB  - Background: Patients with Wilson's disease (WD) present cognitive impairment,
      especially in executive functions. Which other factors might be associated with
      global cognitive decline in these patients remains unclear. Objective: To assess
      which factors are associated with worse performance on a global cognitive test in
      patients with WD. Methods: Twenty patients with WD underwent cognitive assessment
      with the following tests: the Mini-Mental State Examination (MMSE), Dementia
      Rating Scale (DRS), verbal fluency test, brief cognitive battery, clock drawing
      test, Frontal Assessment Battery, Stroop test, Wisconsin card sorting test,
      Hopper test, cubes (WAIS) and the Pfeffer questionnaire. MRI changes were
      quantified. Patients with poor performance on the DRS were compared to patients
      with normal performance. Results: Nine patients had a poor performance on the
      DRS. This group had lower educational level (9.11+/-3.58* 12.82+/-3.06) and a
      greater number of changes on MRI (9.44+/-2.74* 6.27+/-2.45). The presence of
      hyperintensity in the globus pallidus on MRI was more frequent in this group
      (66.6% vs 9.0%), with OR=5.38 (95% CI 0.85-33.86). Conclusion: Global cognitive
      impairment was prevalent in this sample of patients with WD and was associated
      with low educational level, number of changes on MRI and MRI hyperintensity in
      the globus pallidus.

PMID- 29213477
TI  - Telerehabilitation in Parkinson's disease: Influence of cognitive status.
AB  - Background: The need for efficacy in voice rehabilitation in patients with
      Parkinson's disease is well established. Given difficulties traveling from home
      to treatment centers, the use of telerehabilitation may represent an invaluable
      tool for many patients. Objective: To analyze the influence of cognitive
      performance on acceptance of telerehabilitation. Methods: Fifty patients at
      stages 2-4 on the Hoehn-Yahr scale, aged 45-87 years old, with cognitive scores
      of19-30 on the Mini-Mental State Examination, and 4-17 years of education were
      enrolled. All patients were submitted to evaluation of voice intensity pre and
      post in-person treatment with the Lee Silverman Voice Treatment (LSVT) and were
      asked to fill out a questionnaire regarding their preferences between two options
      of treatment and evaluating basic technological competence. Results: Comparisons
      between pre and post-treatment values showed a mean increase of 14dBSPL in vocal
      intensity. When asked about potential acceptance to participate in future
      telerehabilitation, 38 subjects agreed to take part and 12 did not. For these two
      groups, 26% and 17% self-reported technological competence, respectively.
      Agreement to engage in remote therapy was positively associated with years of
      education and cognitive status. Conclusion: Responses to the questionnaire
      submitted after completion of traditional in-person LSVT showed that the majority
      of patients (76%) were willing to participate in future telerehabilitation. Age,
      gender, disease stage and self-reported basic technological skills appeared to
      have no influence on the decision, whereas other factors such as cognitive status
      and higher school education were positively associated with acceptance of the new
      therapy approach.

PMID- 29213478
TI  - Some aspects of the validity of the Montreal Cognitive Assessment (MoCA) for
      evaluating cognitive impairment in Brazilian patients with Parkinson's disease.
AB  - Background: The Montreal Cognitive Assessment (MoCA) is a short global cognitive
      scale, and some studies suggest it is useful for evaluating cognition in patients
      with Parkinson's disease (PD). However, its accuracy has been questioned in
      studies involving patients with low education. Objective: We sought to assess
      whether some of the MoCA subtests contribute to the low accuracy of the test.
      Methods: We performed a cross-sectional retrospective analysis of clinical data
      in a cohort of 71 patients with PD, most with less than 8 years of education.
      Patients were examined using the MDS-UPDRS, Hoehn and Yahr and the MoCA. The data
      were analyzed using mainly descriptive statistics. Results: We analyzed the data
      of 66 patients that were not demented according to the clinical evaluation and
      classified them using the proposed cut-off MoCA scores for diagnosis of MCI and
      dementia. Thirteen patients (19.7%) were classified as having normal cognition,
      24 (36.3%) MCI and 29 (43.9%) dementia. Patients with dementia had longer disease
      duration (p=0.016) and lower education (p=0.0001). Total MoCA scores had a an
      almost normal distribution with a wide range of scores and only one maximum
      score. Performance on the MoCA was highly correlated with education (correlation
      coefficient=0.66, p=0.0001). At least five of the 10 MoCA subtests showed
      significant floor effects. Conclusion: We believe that some of the MoCA subtests
      may be too difficult to be completed by PD patients with low educational level,
      thus contributing to the test's poor diagnostic accuracy.

PMID- 29213479
TI  - The perception of apathy by caregivers of patients with dementia in Parkinson's
      disease.
AB  - Background: Apathy is one of the main neuropsychiatric symptoms in patients with
      Parkinson's disease (PD) and is associated with Parkinson's disease dementia
      (PDD). Objective: To identify the characteristics of apathy in individuals with
      PDD according to caregiver perception. Methods: Thirty-nine patients with PD
      according to MDS criteria for PDD were included. The following scales were used:
      the Hoehn and Yahr, the Unified Parkinson's Disease Rating Scale III, Scales for
      Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), the Montgomery-Asberg
      Depression Rating Scale (MADRS) and the Apathy Evaluation Scale (AES). Results: A
      total of 97.4% of the patients showed results consistent with apathy. Analysis of
      question 14 of the AES revealed no correlation with the total result of all the
      questions [r=-1293, r2=0.0167, 95%CI (-0.4274 to 0.1940), P=0.2162], however,
      there was a correlation of responses to the same question with depression data on
      the MADRS scale [r=-0.5213, r2=0.2718, 95%CI (-0.7186 to -0.2464), P=0.00033].
      Conclusion: Apathy is a disorder associated with PDD. However, the scoring scheme
      of the AES questions can lead to different interpretations of caregiver
      responses, highlighting limitations of the tool for use in studies of PDD.

PMID- 29213480
TI  - Comparison of the use of screening tools for evaluating cognitive impairment in
      patients with Parkinson's disease.
AB  - Background: Screening tests have been used for cognitive deficits in Parkinson's
      disease (PD). Objective: This study compared the Montreal Cognitive Assessment
      (MoCA) test, the Mini-Mental State Examination (MMSE) and the clock drawing test
      for this purpose. Methods: A total of 50 patients with PD were selected, 41 (82%)
      were diagnosed with dementia by the criteria of the Movement Disorder Society.
      The test Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was
      used as the gold standard in comparison with the screening tests. Results: The
      MoCA test (AUC=0.906) had a sensitivity of 87.80% and specificity of 88.89%. When
      the MMSE was associated with the clock drawing test (AUC=0.936), it had a
      specificity of 66.67% and sensitivity of up to 97.56%. Conclusion: The study
      suggests that the MoCA test can be a good screening test in PD. However, MMSE
      associated with the clock drawing test may be more effective than the MoCA test.

PMID- 29213482
TI  - Cerebellum and Cognition Henrietta Leiner's contribution. Historical note.
AB  - The authors present the scientific contribution of Professor Henrietta C. Leiner,
      one of the pioneering scientists in the study of cognitive function of the
      cerebellum.

PMID- 29213481
TI  - The importance of recognizing faciobrachial dystonic seizures in rapidly
      progressive dementias.
AB  - Background: Creutzfeldt-Jakob Disease (CJD) is the prototypical cause of rapidly
      progressive dementia (RPD). Nonetheless, efforts to exclude reversible causes of
      RPD that mimic prion disease are imperative. The recent expanding
      characterization of neurological syndromes associated with antibodies directed
      against neuronal cell surface or sympathic antigens, namely autoimmune
      encephalitis is shifting paradigms in neurology. Such antigens are well known
      proteins and receptors involved in synaptic transmission. Their dysfunction
      results in neuropsychiatric symptoms, psychosis, seizures, movement disorders and
      RPD. Faciobrachial dystonic seizure (FBDS) is a novel characterized type of
      seizure, specific for anti-LGI1 encephalitis. Objective: In order to improve
      clinical recognition we report the cases of two Brazilian patients who presented
      with characteristic FDBS (illustrated by videos) and anti-LGI1 encephalitis.
      Methods: We have included all patients with FBDS and confirmed anti-LGI1
      encephalitis and video records of FDBS in two tertiary Brazilian centers:
      Department of Neurology of Hospital das Clinicas, Sao Paulo University, Sao
      Paulo, Brazil and Hospital Geral de Fortaleza, Fortaleza, Brazil between January
      1, 2011 and December 31, 2015. Results: Both patients presented with clinical
      features of limbic encephalitis associated with FBDS, hyponatremia and normal
      CSF. None of them presented with tumor and both showed a good response after
      immunotherapy. Conclusion: FBDSs may be confounded with myoclonus and occurs
      simultaneously with rapid cognitive decline. Unawareness of FDBS may induce to
      misdiagnosing a treatable cause of RPD as CJD.

PMID- 29213483
TI  - Bipolar disorder, a precursor of Parkinson's disease?
AB  - Parkinson's disease is a neurodegenerative disorder predominantly resulting from
      dopamine depletion in the substantia nigra pars compacta. Some psychiatric
      disorders may have dopaminergic dysfunction as their substrate. We describe a
      well-documented case of Parkinson's disease associated with Bipolar Disorder.
      Although there is some knowledge about the association between these diseases,
      little is known about its pathophysiology and correlation. We believe that among
      various hypotheses, many neurotransmitters are linked to this pathophysiology.

PMID- 29213484
TI  - Percheron thalamopeduncular syndrome with cervical dystonia: A case report.
AB  - Bilateral thalamic infarctions are usually caused by occlusion of the "Artery of
      Percheron" (AoP). Thalamopeduncular syndrome is among the most common
      presentations of AoP occlusion. A 59-year-old male presented abrupt decreased
      level of consciousness. After several weeks, on regaining consciousness, he
      exhibited oculomotor abnormalities, ataxic gait, cervical dystonia, and cognitive
      and behavioral changes. Magnetic resonance imaging disclosed thalamic,
      subthalamic, mammillary and midbrain infarction. Clinical features suggestive of
      bilateral thalamopeduncular syndrome were identified. Besides the presence of
      cognitive impairment and behavioral symptoms, cervical dystonia was evident,
      possibly resulting from interruption of the interconnections among basal ganglia,
      thalamus, subthalamus, midbrain and cerebellum.

PMID- 29213485
TI  - Wernicke's encephalopathy with chorea: Neuroimaging findings.
AB  - We present a case report of motor and cognitive disorders in a 36-year-old woman
      with a history of twelve years of heavy alcohol abuse. The patient presented
      depressive symptoms over the course of one year after a loss in the family,
      evolving with ataxia, bradykinesia and choreiform movements. Progressive
      cognitive decline, sleep alterations and myalgia were also reported during the
      course of disease evolution. Physical examination revealed spastic paraparesis
      with fixed flexion of the hips and knees with important pain upon extension of
      these joints. Initial investigation suggested the diagnosis of thiamine
      deficiency by brain magnetic resonance imaging (MRI).

PMID- 29213486
TI  - Editorial: In the March 2017 issue.

PMID- 29213487
TI  - Traumatic brain injury: An EEG point of view.
AB  - Traumatic brain injury (TBI) is a silent epidemic. Mild traumatic brain injury
      (mTBI) causes brain injury that results in electrophysiologic abnormalities
      visible on electroencephalography (EEG) recordings. The purpose of this brief
      review was to discuss the importance of EEG findings in traumatic brain injury.
      Relevant articles published during the 1996-2016 period were retrieved from
      Medline (PubMed). The keywords were in English and included "traumatic brain
      injury", "EEG" and "quantitative EEG". We found 460 articles, analyzed 52 and
      selected 13 articles. EEG after TBI shows slowing of the posterior dominant
      rhythm and increased diffuse theta slowing, which may revert to normal within
      hours or may clear more slowly over many weeks. There are no clear EEG or
      quantitative EEG (qEEG) features unique to mild traumatic brain injury. Although
      the literature indicates the promise of qEEG in reaching a diagnosis and
      indicating prognosis of mTBI, further study is needed to corroborate and refine
      these methods.

PMID- 29213488
TI  - Scoring systems for the Clock Drawing Test: A historical review.
AB  - The Clock Drawing Test (CDT) is a simple neuropsychological screening instrument
      that is well accepted by patients and has solid psychometric properties. Several
      different CDT scoring methods have been developed, but no consensus has been
      reached regarding which scoring method is the most accurate. This article reviews
      the literature on these scoring systems and the changes they have undergone over
      the years. Historically, different types of scoring systems emerged. Initially,
      the focus was on screening for dementia, and the methods were both quantitative
      and semi-quantitative. Later, the need for an early diagnosis called for a
      scoring system that can detect subtle errors, especially those related to
      executive function. Therefore, qualitative analyses began to be used for both
      differential and early diagnoses of dementia. A widely used qualitative method
      was proposed by Rouleau et al. (1992). Tracing the historical path of these
      scoring methods is important for developing additional scoring systems and
      furthering dementia prevention research.

PMID- 29213489
TI  - In search of the moral-psychological and neuroevolutionary basis of political
      partisanship.
AB  - In many countries, a radical political divide brings several socially relevant
      decisions to a standstill. Could cognitive, affective and social (CAS)
      neuroscience help better understand these questions? The present article reviews
      the moral-psychological and neuroevolutionary basis of the political partisanship
      divide. A non-systematic literature review and a conceptual analysis were
      conducted. Three main points are identified and discussed: 1) Political partisan
      behavior rests upon deep moral emotions. It is automatically processed and
      impervious to contradiction. The moral motifs characterizing political
      partisanship are epigenetically set across different cultures;2) partisanship is
      linked to personality traits, whose neural foundations are associated with moral
      feelings and judgement;3) Self-deception is a major characteristic of political
      partisanship that probably evolved as an evolutionary adaptive strategy to deal
      with the intragroup-extragroup dynamics of human evolution. CAS neuroscience
      evidence may not resolve the political divide, but can contribute to a better
      understanding of its biological foundations.

PMID- 29213490
TI  - Neuropathological findings in entorhinal cortex of subjects aged 50 years or
      older and their correlation with dementia in a sample from Southern Brazil.
AB  - Introduction: The aims of this study were to survey neurodegenerative changes
      detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects
      aged 50 years or older and to correlate these findings with suspected dementia,
      as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the
      Elderly). Methods: Fourteen brains were submitted to the immunohistochemistry
      technique for different proteins (beta-amyloid, tau, alpha-synuclein and phospho
      TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven
      percent of the individuals exhibited IQCODE results compatible with dementia,
      being classified into the demented group (DG): 87.5% of patients had
      neuropathological findings corresponding to Alzheimer's-like brain pathology
      (ALBP). Of the patients in the non-demented group (NDG), 16.7% met
      neuropathological criteria for ALBP. All individuals in the DG showed deposits of
      more than one kind of protein in the EC. The most common association was
      hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most
      individuals with dementia had neuropathological findings of ALBP, as did one
      individual with no signs of dementia, characterizing a preclinical stage. The
      results of this study suggest that deposits of a single type of anomalous protein
      are normal findings in an aging brain, while more than one kind of protein or the
      combined presence of anomalous protein deposits indicate the presence of
      dementia.

PMID- 29213491
TI  - Prevalence of functional cognitive impairment and associated factors in Brazilian
      community-dwelling older adults.
AB  - : The identification of the prevalence of cognitive impairment and associated
      factors among older adults is important in countries facing rapid demographic
      transition, given the significant implications for public policy and health
      planning. Objective: To determine the prevalence of functional cognitive
      impairment (FCI) and associated factors in Brazilian community-dwelling older
      adults. Methods: A cross-sectional study involving 461 elderly subjects residing
      in Fortaleza city, Ceara was conducted. Cognitive assessment was performed using
      three tests: the MMSE (Mini-Mental State Examination), VF (Verbal Fluency) and CT
      (Clock Test). The functional capacity evaluation was based on a survey of 21
      basic and instrumental activities of daily living (ADLs). Cognitive impairment
      was defined by MMSE cut-off points adjusted for literacy. Functional impairment
      was defined as dependency to carry out more than four ADLs. Results: The
      prevalence of FCI was 13.64% (95% CI: 10.33 to 16.64%). FCI was proportionally
      associated with age with OR=2.24 (95% CI: 1.04 to 4.79) for individuals aged 70
      to 79 years and OR=8.27 (95 % CI: 4.27 to 16.4) for those aged 80 to 100 years.
      FCI was associated with self-reported diseases including hypertension OR=2.06
      (95% CI: 1.17 to 3.65), stroke OR=2.88 (95% CI: 1.66 to 5.00) and acute
      myocardial infarction OR=2.94 (95% CI: 1.59 to 5.42). The occurrence of FCI was
      proportionally correlated with the number of drugs used. Conclusion: Functional
      cognitive impairment is a prevalent condition in Brazilian community-dwelling
      older adults and its occurrence is associated with age, number of drugs used, and
      vascular morbidities.

PMID- 29213492
TI  - Bells Test: Are there differences in performance between adult groups aged 40-59
      and 60-75?
AB  - Objective: To verify whether differences exist between groups of Brazilian adults
      aged 40-59 and 60-75 in respective performance on the Bells Test, given the
      dearth of literature investigating the relationship between focused visual
      attention and the age factor. Methods: Eighty-four neurologically healthy adults
      (half aged 40-59 and half 60-75) with high educational level (40-59 years group:
      M=17.75 years' education; SD=4.00; 60-75 years group: M=15.85 years education;
      SD=3.19) were assessed using the Bells Test. Data on accuracy and processing
      speed were compared between groups by ANCOVA, controlled for the covariates
      education and frequency of reading and writing habits. Results: There were no
      significant differences between the age groups. Conclusion: It is suggested that
      aging influences sustained and focused attention and speed processing after 75
      years of age on visual cancellation paradigms, when executive and attentional
      changes tend to be more marked. Further studies should investigate healthy older
      and oldest-old adults, as well as groups with low and intermediate educational
      backgrounds. In addition, Brazilian clinical populations should also be
      characterized, particularly those with neurological disorders that might have
      visual hemineglect.

PMID- 29213493
TI  - Normative data for the Brief Cognitive Screening Battery stratified by age and
      education.
AB  - Introduction: Diagnosing neurocognitive disorders is challenging in low-educated
      individuals. Objective: To report normative data for the Brief Cognitive
      Screening Battery (BCSB) and to assess the association of age and education with
      performance on the BCSB in 240 community-dwelling elderly from Ermelino
      Matarazzo, Sao Paulo city. Methods: The inclusion criteria were scoring above the
      education-adjusted cut-off points on the Mini-Mental State Examination (MMSE) and
      below six points on the Geriatric Depression Scale (GDS). Results: Age was
      associated with performance on the Naming, Incidental Memory, Verbal Fluency,
      Clock Drawing Test, Delayed Recall and Recognition subtests. Education was
      associated with performance on Naming, Recognition, Verbal Fluency and the Clock
      Drawing Test. Conclusion: The normative values reported are relevant for
      diagnosing neurocognitive disorders in low-educated elderly.

PMID- 29213494
TI  - Performance on cognitive tests, instrumental activities of daily living and
      depressive symptoms of a community-based sample of elderly adults in Rio de
      Janeiro, Brazil.
AB  - Objective: To describe the performance on basic cognitive tasks, instrumental
      activities of daily living, and depressive symptoms of a community-based sample
      of elderly adults in Rio de Janeiro (Brazil) who participated in multiple
      physical, social, and cognitive activities at government-run community centers.
      Methods: A total of 264 educated older adults (> 60 years of age of both genders)
      were evaluated by the Brief Cognitive Screening Battery (BCSB), Lawton's and
      Pfeffer's activities of daily living indexes, and the Geriatric Depressive Scale
      (GDS). Results: The mean age of the sample was 75.7 years. The participants had a
      mean of 9.3 years of formal education. With the exception of the Clock Drawing
      Test (CDT), mean scores on the cognitive tests were consistent with the values in
      the literature. Only 6.4% of the sample had some kind of dependence for
      activities of daily living. The results of the Geriatric Depression Scale (GDS
      15) indicated mild symptoms of depression in 16.8% of the sample. Conclusion:
      This study provided important demographic, cognitive, and functional
      characteristics of a specific community-based sample of elderly adults in Rio de
      Janeiro, Brazil.

PMID- 29213495
TI  - Impact of sociodemographic variables on executive functions.
AB  - : Executive functions (EFs) regulate human behavior and allow individuals to
      interact and act in the world. EFs are sensitive to sociodemographic variables
      such as age, which promotes their decline, and to others that can exert a
      neuroprotective effect. Objective: To assess the predictive role of education,
      occupation and family income on decline in executive functions among a sample
      with a wide age range. Methods: A total of 925 participants aged 18-89 years with
      1-28 years' education were submitted to assessment of executive functions using
      the Card Sorting Test (CST), Phonemic Verbal Fluency (FAS) Task and Semantic
      Verbal Fluency (SVF) Task. Data on income, occupation and educational level were
      collected for the sample. The data were analyzed using Linear Regression, as well
      as Pearson's and Spearman's Correlation. Results: Age showed a significant
      negative correlation (p<0.001) with performance on the CST, FAS and SVF, whereas
      education, income and occupation were positively associated (p<0.001) with the
      tasks applied. After application of the multivariate linear regression model, a
      significant positive relationship with the FAS was maintained only for education
      (p<0.001) and income (p<0.001). The negative relationship of age (p<0.001) and
      positive relationship of both education (p<0.001) and income (p<0.001and p=0.003)
      were evident on the CST and SVF. Conclusion: Educational level and income
      positively influenced participants' results on executive function tests,
      attenuating expected decline for age. However, no relationship was found between
      occupation and the cognitive variables investigated.

PMID- 29213496
TI  - Effects of a cognitive training program and sleep hygiene for executive functions
      and sleep quality in healthy elderly.
AB  - Introduction: The aging process causes changes in the sleep-wake cycle and
      cognition, especially executive functions. Interventions are required to minimize
      the impact of the losses caused by the aging process. Objective: To evaluate the
      effects of a cognitive training program and psychoeducation on sleep hygiene
      techniques for executive functions and sleep quality in healthy elderly. Methods:
      The participants were 41 healthy elderly randomized into four groups ([CG]
      control group, cognitive training group [CTG], sleep hygiene group [SHG] and
      cognitive training and hygiene group [THG]). The study was conducted in three
      stages:1st - assessment of cognition and sleep;2nd - specific intervention for
      each group;3rd - post-intervention assessment. Results: The results showed that
      the CTG had significant improvements in cognitive flexibility tasks, planning,
      verbal fluency and episodic memory, gains in sleep quality and decreased
      excessive daytime sleepiness. The SHG also had improved sleep quality, excessive
      daytime sleepiness and significant improvements in insights, planning, attention
      and episodic memory. The THG had significant gains in cognitive flexibility,
      problem solving, verbal fluency, attention and episodic memory. Conclusion:
      Cognitive training and sleep hygiene interventions were useful strategies for
      improving cognitive performance and sleep quality of healthy elderly, but there
      was no evidence that sessions combining cognitive training and psychoeducation on
      sleep hygiene enhanced the gains provided by these interventions applied
      individually.

PMID- 29213497
TI  - Development and content validity of the CENA Program for Educational Training on
      the Neuropsychology of Learning, with an emphasis on executive functions and
      attention.
AB  - Introduction: The importance of executive functions (EF) in childhood
      development, and their role as indicators of health, well-being, professional and
      academic success have been demonstrated by several studies in the literature. FE
      are cognitive processes that aim to control and manage behavior to achieve
      specific goal and included skills planning, inhibition, cognitive flexibility,
      (executive) attention and the central executive component of working memory (WM).
      In the context of education, the EF are crucial for continued learning and
      efficient academic performance due to their involvement in several components of
      the educational process. Objective: The aim of this article was to describe the
      development and content validity of the CENA Program for Educational Training on
      the Neuropsychology of Learning, with an emphasis on executive functions and
      attention. Methods: The study involved seven specialists (four responsible for
      evaluating the program, and three involved in brainstorming), and was carried out
      in three stages:Background research: neuropsychology and education;Program
      development - author brainstorming andEvaluation by expert judges The goals,
      language and methods. Results: CENA Program were considered adequate, attesting
      to its content validity as a school-based neuropsychological intervention.
      Conclusion: Teacher training in school neuropsychology may be an important area
      for future investment and contribute to academic achievement and student
      development in the Brazilian education system.

PMID- 29213499
TI  - An interdisciplinary approach aiding the diagnosis of primary progressive
      aphasia: A case report.
AB  - Frontotemporal dementia (FTD) is one of the most common causes of early-onset
      dementia with primary progressive aphasia (PPA) being the second-most-frequent
      form of this degenerative disease. Despite the similarity with progressive
      dementia (especially in early stages of Alzheimer's disease), three types of PPA
      can be differentiated: semantic, agrammatic and logopenic (subtype discussed in
      this study). To date, no medications have been shown to improve or stabilize
      cognitive deficits in patients with PPA. We report the case of a 62-year-old
      woman with difficulty naming objects and planning. An interdisciplinary
      evaluation, including imaging and lab exams, together with neuropsychological and
      personality assessments, confirmed that the patient had logopenic PPA on the
      basis of repetition difficulty, phonemic and semantic paraphasias and absence of
      agrammatism. The timing of the assessment in this case, along with the resources
      available and commitment of an integrated interdisciplinary team, allowed a
      differential diagnosis (from other classical dementias) to be reached.

PMID- 29213500
TI  - Editorial: In the June 2017 issue.

PMID- 29213498
TI  - Program of neuropsychological stimulation of cognition in students: Emphasis on
      executive functions - development and evidence of content validity.
AB  - Objective: The goal of this study was to describe the construction process and
      content validity evidence of an early and preventive intervention program for
      stimulating executive functions (EF) in Elementary School children within the
      school environment. Methods: The process has followed the recommended steps for
      creating neuropsychological instruments: internal phase of program organization,
      with literature search and analyses of available materials in the classroom;
      program construction; analysis by expert judges; data integration and program
      finalization. To determine the level of agreement among the judges, a Content
      Validity Index (CVI) was calculated. Results: Content validity was evidenced by
      the agreement among the experts with regards to the program, both in general and
      for each activity. All steps taken were deemed necessary because they contributed
      to the identification of positive aspects and possible flaws in the process.
      Conclusion: The steps also helped to adapt stimuli and improve program tasks and
      activities. Methodological procedures implemented in this study can be adopted by
      other researchers to create or adapt neuropsychological stimulation and
      rehabilitation programs. Furthermore, the methodological approach allows the
      reader to understand, in detail, the technical and scientific rigor adopted in
      devising this program.

PMID- 29213502
TI  - Effect of educational status on performance of older adults in digital cognitive
      tasks: A systematic review.
AB  - : As people age, cognitive abilities may decline resulting in serious
      disabilities. Neuropsychological instruments can provide information on the
      cognitive state of older adults. Researchers worldwide have been using digital
      cognitive tests to assess cognitive domains. Objective: To determine whether
      educational status affects the performance of older adults on digital cognitive
      tasks. Methods: A systematic review of articles in English, Portuguese, or
      Spanish published in the last 5 years was conducted. The databases searched were
      SCOPUS, PubMed, Lilacs, Scielo and PsychInfo. The PRISMA method was used.
      Results: A total of 7,089 articles were initially retrieved. After search and
      exclusion with justification, seven articles were selected for further review.
      Conclusion: The findings revealed that researchers using digital tasks generally
      employed paper-based tests to compare results. Also, no association between years
      of education and test performance was found. Finally, a dearth of studies using
      digital tests published by Brazilian researchers was evident.

PMID- 29213501
TI  - Type 2 diabetes mellitus in the pathophysiology of Alzheimer's disease.
AB  - Both Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are two common
      forms of disease worldwide and many studies indicate that people with diabetes,
      especially DM, are at higher risk of developing AD. AD is characterized by
      progressive cognitive decline and accumulation of beta-amyloid (Abeta) forming
      senile plaques. DM is a metabolic disorder characterized by hyperglycemia in the
      context of insulin resistance and relative lack of insulin. Both diseases also
      share common characteristics such as loss of cognitive function and inflammation.
      Inflammation resulting from Abeta further induces production of Abeta1-42
      peptides. Inflammation due to overnutrition induces insulin resistance and
      consequently DM. Memory deficit and a decrease in GLUT4 and hippocampal insulin
      signaling have been observed in animal models of insulin resistance. The
      objective of this review was to show the shared characteristics of AD and DM.

PMID- 29213503
TI  - Cognitive assessment: A challenge for occupational therapists in Brazil.
AB  - : Cognitive impairment is a common dysfunction after neurological injury.
      Cognitive assessment tools can help the therapist understand how impairments are
      affecting functional status and quality of life. Objective: The aim of the study
      was to identify instruments for cognitive assessment that Occupational Therapists
      (OT) can use in clinical practice. Methods: The instruments published in English
      and Portuguese between 1999 and 2016 were systematically reviewed. Results: The
      search identified 17 specific instruments for OT not validated in Brazilian
      Portuguese, 10 non-specific instruments for OT not validated in Brazilian
      Portuguese, and 25 instruments validated for Portuguese, only one of which was
      specific for OT (Lowenstein Occupational Therapy Cognitive Assessment).
      Conclusion: There are few assessment cognitive tools validated for use in the
      Brazilian culture and language. The majority of the instruments appear not to be
      validated for use by OT in clinical practice.

PMID- 29213504
TI  - Utility of the Neuropsychiatric Inventory Questionnaire (NPI-Q) in the assessment
      of a sample of patients with Alzheimer's disease in Chile.
AB  - : The Neuropsychiatric Inventory Questionnaire (NPI-Q) is an informant-based
      instrument that measures the presence and severity of 12 Neuropsychiatric
      Symptoms (NPS) in patients with dementia, as well as informant distress.
      Objective: To measure the psychometric properties of the NPI-Q and the prevalence
      of NPS in patients with Alzheimer's disease (AD) in Chile. Methods: 53 patients
      with AD were assessed. Subjects were divided into two different groups: mild AD
      (n=26) and moderate AD (n=27). Convergent validity was estimated by correlating
      the outcomes of the NPI-Q with Neuropsychiatric Inventory (NPI) scores and with a
      global cognitive efficiency test (Addenbrooke's Cognitive Examination - Revised -
      ACE-R). Reliability of the NPI-Q was analysed by calculating its internal
      consistency. Prevalence of NPS was estimated with both the NPI and NPI-Q.
      Results: Positive and significant correlations were observed between the NPI-Q,
      the NPI, and the ACE-R (r=0.730; p<0.01 and 0.315; p<0.05 respectively). The
      instrument displayed an adequate level of reliability (Cronbach's alpha=0.783).
      The most prevalent NPS were apathy/indifference (62.3%) and dysphoria/depression
      (58.5%). Conclusion: The NPI-Q exhibited acceptable validity and reliability
      indicators for patients with AD in Chile, indicating that it is a suitable
      instrument for the routine assessment of NPS in clinical practice.

PMID- 29213506
TI  - Symptoms of depression in patients with mild cognitive impairment in Parkinson's
      disease.
AB  - Objective: To investigate the most frequent depressive symptoms and their
      association with cognition in Parkinson's disease (PD) patients with mild
      cognitive impairment (MCI). Methods: 48 patients with PD and 44 controls (CG),
      aged between 50 and 80 years and with at least 4 years of formal education, all
      with MCI and none diagnosed with depression, were assessed. Patients and controls
      were matched for age, education, and Mini-Mental State Examination (MMSE) score.
      Participants underwent clinical evaluation with a neurologist followed by
      neuropsychological assessment employing the instruments: MMSE, Clock Drawing
      Test, Verbal Fluency Test (semantic and phonemic), Figures Memory Test (FMT),
      Stroop Test, Trail Making Test, Digit Span (WAIS III), Rey Auditory Verbal
      Learning Test (RAVLT), Hooper Visual Organization Test, and Beck Depression
      Inventory (BDI). Results: The most frequent depressive symptoms in the PD group
      were: difficulty working, fatigue and sleep disorders (the latter also being
      present in CG). BDI score correlated negatively with learning and recognition
      memory in both groups. Episodic memory, evaluated by the FMT and RAVLT tests, was
      the cognitive function showing greatest impairment. Conclusion: Some of the
      depressive symptoms observed in PD patients with MCI seem to be attributable to
      complications of PD, while others are common to both PD and MCI, making
      differential diagnoses complex but crucial.

PMID- 29213505
TI  - Planning ability impairments in probable Alzheimer's disease patients: Evidence
      from the Tower of London test.
AB  - : Alzheimer's disease (AD) is associated with progressive impairment of higher
      level cognitive abilities. Previous research suggests that early impairment of
      executive functions occurs during the course of the disease, but few studies have
      specifically investigated planning ability in an AD population. Objective: The
      purpose of the current study was to examine whether AD patients retain the
      ability to plan ahead, by analyzing specificities of their behavior in
      successfully achieving a pre-established goal. Methods: Twenty-one AD patients
      and thirty-three elderly controls underwent a problem-solving assessment using
      the Tower of London (TOL) test. Results: AD patients were less accurate and less
      efficient than controls. AD patients also committed more mistakes. This indicates
      a decline in working memory and inhibitory deficits, resulting in impulsive and
      inappropriate behaviors. Conclusion: These results are in agreement with previous
      studies, showing executive function problems in patients with AD. Specifically,
      this study demonstrates the presence of planning ability deficits in AD,
      considering both qualitative and quantitative approaches. The wide range of
      analysis presented in this study can aid clinicians in identifying the nature of
      the poor performance of AD patients during a planning task.

PMID- 29213508
TI  - Cross-cultural adaptation of the "Australian National University Alzheimer's
      Disease Risk Index" for the Brazilian population.
AB  - : Alzheimer's disease (AD) represents a major public health problem and it is
      therefore crucial that modifiable risk factors be known prior to onset of
      dementia in late-life. The "Australian National University - Alzheimer's Disease
      Risk Index" (ANU-ADRI) is one of the potential tools for primary prevention of
      the disease. Objective: The aim of this study was to devise an adapted version of
      the ANU-ADRI for use in Brazil. Methods: The instrument was translated from its
      original language of English into Portuguese and then back-translated into
      English by bilingual translators. It was subsequently reviewed and evaluated as
      to the degree of translation issues and equivalence. In this study, the ANU-ADRI
      was applied using individual (face-to-face) interviews in a public hospital,
      unlike the original version which is applied online by self-report. The final
      version (pretest) was evaluated in a sample of 10 participants with a mean age of
      60 years (+/-11.46) and mean education of 11 years (+/-6.32). Results: The
      intraclass correlation coefficient (ICC) (inter-rater) was 0.954 (P<0.001 for a
      confidence interval (CI) of 95%=[0.932; 0.969]). Cultural equivalence was
      performed without the need for a second instrument application step. Conclusion:
      After cross-cultural adaptation, the language of the resultant questionnaire was
      deemed easily understandable by the Brazilian population.

PMID- 29213507
TI  - Sundown syndrome and symptoms of anxiety and depression in hospitalized elderly.
AB  - : Sundown syndrome is characterized by the sudden appearance of neuropsychiatric
      symptoms such as agitation, confusion and anxiety in a chronologic fashion,
      usually during late afternoon or early evening. Objective: To evaluate the
      prevalence of sundown syndrome in university hospital wards and its relationship
      with anxiety/depression symptoms, cognitive decline, and clinical and demographic
      variables. Methods: We evaluated 70 patients admitted to the Lauro Wanderley
      University Hospital (HULW), Joao Pessoa-PB, Brazil. Data collection instruments
      were the Confusion Assessment Method (CAM), the Mini-Mental State Exam (MMSE) and
      the Hospital Anxiety and Depression Scale (HADS). Results: Mean patient age was
      68.4+/-6.4 years, 55.7% were male, 67.1% were illiterate or had incomplete
      primary education. It was observed that 14.3% of patients had delirium, 15.7% had
      cognitive deficits, while 21.4% and 18.6% had anxious and depressive symptoms,
      respectively. The age of patients with delirium (71.9+/-8.7) was significantly
      higher than those without (67.8+/-5.8). At 95% confidence, there was a
      significant difference in the groups with and without delirium for the MMSE and
      HADS-D scales. Conclusion: We verified the occurrence of delirium compatible with
      the sundown syndrome and associated with depressive symptoms and cognitive
      deficit, with no apparent relationship with infectious processes or fever, number
      of drugs used, hospital stay or anxious symptomatology.

PMID- 29213509
TI  - Comparative analysis of the electroencephalogram in patients with Alzheimer's
      disease, diffuse axonal injury patients and healthy controls using LORETA
      analysis.
AB  - : Alzheimer's disease (AD) is a dementia that affects a large contingent of the
      elderly population characterized by the presence of neurofibrillary tangles and
      senile plaques. Traumatic brain injury (TBI) is a non-degenerative injury caused
      by an external mechanical force. One of the main causes of TBI is diffuse axonal
      injury (DAI), promoted by acceleration-deceleration mechanisms. Objective: To
      understand the electroencephalographic differences in functional mechanisms
      between AD and DAI groups. Methods: The study included 20 subjects with AD, 19
      with DAI and 17 healthy adults submitted to high resolution EEG with 128
      channels. Cortical sources of EEG rhythms were estimated by exact low-resolution
      electromagnetic tomography (eLORETA) analysis. Results: The eLORETA analysis
      showed that, in comparison to the control (CTL) group, the AD group had increased
      theta activity in the parietal and frontal lobes and decreased alpha 2 activity
      in the parietal, frontal, limbic and occipital lobes. In comparison to the CTL
      group, the DAI group had increased theta activity in the limbic, occipital
      sublobar and temporal areas. Conclusion: The results suggest that individuals
      with AD and DAI have impairment of electrical activity in areas important for
      memory and learning.

PMID- 29213510
TI  - Actively station: Effects on global cognition of mature adults and healthy
      elderly program using eletronic games.
AB  - : Studies show that aging is accompanied by decline in cognitive functions but
      also indicate that interventions, such as training on electronic games, can
      enhance performance and promote maintenance of cognitive abilities in healthy
      older adults. Objective: To investigate the effects of an electronic game
      program, called Actively Station, on the performance of global cognition of
      adults aged over 50 years. Methods: 124 mature and elderly adults enrolled in the
      "Actively Station" cognitive stimulation program of Sao Caetano do Sul City, in
      the State of Sao Paulo, participated in training for learning of electronic
      games. Participants were divided into two groups: training group (TG) n=102 and
      control group (CG) n=22. Protocol: a sociodemographic questionnaire, the Mini
      Mental State Examination (MMSE), the Addenbrooke's Cognitive Examination Revised
      (ACE-R), the Memory Complaint Questionnaire (MAC-Q), the scale of frequency of
      forgetfulness, the Geriatric Depression Scale (GDS-15), the Geriatric Anxiety
      Inventory (GAI), the Global Satisfaction with Life Scale, and two scales on
      learning in the training. Results: The cognitive performance of the TG improved
      significantly after the program, particularly in the domains of language and
      memory, and there was a decrease on the anxiety index and frequency of memory
      complaints, when compared to the CG. Conclusion: These findings suggest that the
      acquisition of new knowledge and the use of new stimuli, such as electronic
      games, can promote improvements in cognition and mood and reduce the frequency of
      memory complaints.

PMID- 29213511
TI  - Lewy and his inclusion bodies: Discovery and rejection.
AB  - Fritz Jacob Heinrich Lewy described the pathology of Paralysis agitans [Parkinson
      disease] and was the first to identify eosinophilic inclusion bodies in neurons
      of certain brain nuclei, later known as Lewy bodies, the pathological signature
      of the Lewy body diseases. In 1912, he published his seminal study, followed soon
      after by an update paper, and 10 years later, in 1923, by his voluminous book,
      where he exhaustively described the subject. The publication provided extensive
      information on the pathology of Paralysis agitans, and the entirely novel finding
      of eosinophilic inclusion bodies, which would become widely recognized and
      debated in the future. His discovery was acknowledged by important researchers
      who even named the structure after him. However, after his last publication on
      the issue, inexplicably, he never mentioned his histopathological discovery
      again. Despite several hypotheses, the reasons that led him to neglect (reject)
      the structure which he so preeminently described have remained elusive.

PMID- 29213512
TI  - Transient Gerstmann syndrome as manifestation of stroke: Case report and brief
      literature review.
AB  - Gerstmann Syndrome (GS) is a rare neurological condition described as a group of
      cognitive changes corresponding to a tetrad of symptoms comprising agraphia,
      acalculia, right-left disorientation and finger agnosia. It is known that some
      specific brain lesions may lead to such findings, particularly when there is
      impairment of the angular gyrus and adjacent structures. In addition, the
      possibility of disconnection syndrome should be considered in some cases. The
      purpose of this article is to report a case of a young, cardiac patient, non
      adherent to treatment, who presented with a stroke in which transient clinical
      symptoms were compatible with the tetrad of GS. The case report is followed by a
      discussion and brief review of the relevant literature.

PMID- 29213513
TI  - Prolonged delirium misdiagnosed as a mood disorder.
AB  - Delirium can be conceptualized as an acute decline in cognitive function that
      typically lasts from hours to a few days. Prolonged delirium can also affect
      patients with multiple predisposing and/or precipitating factors. In clinical
      practice, prolonged delirium is often unrecognized, and can be misdiagnosed as
      other psychiatric disorders. We describe a case of a 59-year-old male presenting
      with behavioral and cognitive symptoms that was first misdiagnosed as a mood
      disorder in a general hospital setting. After prolonged delirium due to multiple
      factors was confirmed, the patient was treated accordingly with symptomatic
      management. He evolved with progressive improvement of his clinical status. Early
      diagnosis and management of prolonged delirium are important to improve patient
      prognosis and avoid iatrogenic measures.

PMID- 29213514
TI  - Catatonia, beyond a psychiatric syndrome.
AB  - Although catatonia is a well-known psychiatric syndrome, there are many possible
      systemic and neurological etiologies. The aim of this case report was to present
      a case of a patient with cerebral venous sinus thrombosis and infarction in which
      catatonia was the clinical manifestation of a possible nonconvulsive status
      epilepticus. To our knowledge, only one such case has been reported in the
      literature, which had a simplified diagnostic investigation. It is important to
      correctly recognize the organic cause underlying catatonia in order to treat the
      patient as soon as possible thereby improving outcome. Therefore, physicians need
      to update their knowledge on catatonia, recognizing that it can be part of a
      psychiatric or neurologic condition.

PMID- 29213515
TI  - Rehabilitation in severe memory deficit: A case study.
AB  - The term amnesia refers to a pathological state of mind in which memory and
      learning are affected to a greater extent than other cognitive functions in a
      patient without altered level of consciousness. The aim of the current study was
      to describe a case of severe amnesia in a patient during neurological
      rehabilitation and to report the importance of preserved cognitive functions to
      compensate for the mnemonic deficit. VJA presented a clinical condition
      suggestive of encephalopathy due to caloric-protein malnutrition following
      several abdominal surgical procedures for complicated choledocholithiasis. A
      descriptive analysis of the results was carried out to outline the goals attained
      and the factors limiting implementation of memory aids. After the intervention
      program, consisting of individual and group activities, VJA showed improvement in
      level of recall with repetition of tasks, but still required constant external
      monitoring. Longitudinal follow-up is necessary to obtain more consistent
      results.

PMID- 29213516
TI  - In the September 2017 issue.

PMID- 29213517
TI  - Soccer (Football Association) and chronic traumatic encephalopathy: A short
      review and recommendation.
AB  - Chronic traumatic encephalopathy (CTE) was initially described in boxers, but in
      recent years it has been reported in other settings, particularly in contact
      sports and military personnel. Soccer (football association) had previously been
      (and still is) considered relatively safe when compared to other sports, such as
      American football. However, a few cases of professional soccer players with CTE
      have been reported in the last few years. It is still unknown how frequent this
      condition is in soccer players, and the role played by heading the ball remains
      elusive. Other traumas to the head, face and neck caused by contact with another
      player's head, arm or other body parts are among the most frequent in soccer. In
      spite of the lack of more in-depth knowledge, there is reasonable evidence for
      recommending severe punishment (red card and suspension for several matches) for
      players causing avoidable trauma to another player's head.

PMID- 29213518
TI  - Cognitive impairment of patients with chronic renal disease on hemodialysis and
      its relationship with sociodemographic and clinical characteristics.
AB  - : Cognitive impairment and dementia commonly occur in individuals with chronic
      kidney disease, especially in advanced stages, but are still poorly diagnosed.
      OBJECTIVE: To evaluate the cognitive ability of patients with chronic kidney
      disease on hemodialysis and its relationship with sociodemographic and clinical
      characteristics. METHODS: A cross-sectional study was carried out in a Renal
      Replacement Therapy Unit in the interior of the State of Sao Paulo involving 99
      patients. The data were collected through an individual interview, using the
      Sociodemographic and Clinical Characterization questionnaires and the
      Addenbrooke's Cognitive Examination - Revised (ACE-R) questionnaire. RESULTS:
      Participants were predominantly male, with a mean age of 54.68 years. The mean
      ACE-R score was 64.26 points, and 76.76% of patients had lower-than-expected
      scores, suggesting the presence of cognitive impairment. A moderate, negative
      correlation was found between total score on the ACE-R and age (r= -0.38,
      p<=0.001), a moderate positive correlation with years of education (r=0.52,
      p<=0.001), and a weak positive correlation of total score with hemodialysis time
      (r=0.26, p<=0.001). CONCLUSION: A relationship was found between cognitive
      ability and age, years of education and hemodialysis time, suggesting that
      individuals who were older, had less education and longer hemodialysis time
      presented greater cognitive impairment.

PMID- 29213519
TI  - Language and communication non-pharmacological interventions in patients with
      Alzheimer's disease: a systematic review. Communication intervention in
      Alzheimer.
AB  - : Alzheimer's disease considerably compromises communication skills. Language
      changes become more prominent as the disease progresses. Deterioration of
      language and cognition reduces the ability of holding conversations, which has a
      negative impact on social interaction. OBJECTIVE: To conduct a systematic review
      of the literature for articles reporting interventions focused on the language
      and communication of people with Alzheimer's disease (AD) without use of
      medication. METHODS: We performed a search using the keywords Alzheimer's
      disease, language, communication, cognition, cognitive intervention,
      rehabilitation and therapy, and their corresponding Portuguese and Spanish terms,
      on the SciELO, LILACS, PubMed and PsychINFO databases. We analyzed intervention
      studies published from 1993 to 2016 that involved stimulation of language skills
      and/or communication with pre-and post-intervention quantitative results, and
      whose samples included at least 50% with a diagnosis of probable AD. Studies were
      analyzed and classified into four levels of evidence, according to the criteria
      described in the literature. RESULTS: Twenty-eight articles were included. The
      majority of the designs had medium-to-low scientific evidence. Most interventions
      showed benefits for at least one language or communicative skill. Eight types of
      interventions emerged from the analysis of the studies. Further research with
      higher levels of evidence is recommended in the investigation of interventions
      focused on language and communication skills of patients with dementia.
      CONCLUSION: Studies with high levels of evidence on the topic investigated are
      only being conducted on a small scale. Two intervention techniques seem
      potentially effective: lexical-semantic approaches and interventions that work
      with different cognitive skills (including language).

PMID- 29213520
TI  - Brazilian transcultural adaptation of an instrument on communicative strategies
      of caregivers of elderly with dementia.
AB  - : Communication with patients with dementia may be a difficult task for
      caregivers. OBJECTIVE: The aim of this study was to produce a Brazilian
      transcultural adaptation of an instrument developed in Canada, called the Small
      Communication Strategies Scale, composed of 10 items constructed from 10
      communicative strategies most recurrent in a literature survey. METHODS: Drawing
      on understanding of the construction of the Small Communication Strategies Scale
      (SCSS), a Brazilian Portuguese version of the instrument was devised through the
      following steps: translation, back-translation and semantic-cultural adaptation
      by a specialized linguist in English-Portuguese translations and application of
      the comprehension test for the version produced in a group of caregivers of
      elderly individuals with dementia. RESULTS: The transcultural equivalence process
      was performed and two items of the SCSS needed adapting to the Brazilian context.
      After changes suggested by a specialized linguist, the final version was applied
      to 34 caregivers and the transcultural equivalence considered satisfactory.
      CONCLUSION: The Brazilian version of the instrument was successfully
      transculturally adapted for future validation and application in Brazil.

PMID- 29213521
TI  - Distinct Phospho-TDP-43 brain distribution in two cases of FTD, one associated
      with ALS.
AB  - INTRODUCTION: TDP-43 is an intranuclear protein involved in many cellular
      processes. When altered, it shows a change in pattern of distribution, as well as
      in functioning, throughout the Central Nervous System structures. Frontotemporal
      Lobar Degeneration (FTLD) and Amyotrophic Lateral Sclerosis (ALS) are examples of
      TDP-43 proteinopathy. These disorders form a clinical spectrum, with some
      patients having a pure cognitive disorder while others also exhibit motor
      features. METHODS: We studied two donated brains from patients with a diagnosis
      of Frontotemporal Dementia (FTD), one of which was associated with ALS (ALS-FTD).
      After fixation and macroscopic examinations, sample analyses were performed.
      Specific regions were chosen for the application of immunohistochemistry (IHC)
      with anti-Abeta, AT8, anti-alpha-synuclein and anti-phospho-TDP-43. RESULTS: Both
      brains presented anti-phospho-TDP-43 positivity, but this was not equally
      distributed throughout the encephalic zones. In the FTD case, the studied brain
      presented phosphorylated TDP-43- in the frontal cortex, hippocampus, entorhinal
      cortex and mesencephalon; in the ALS-FTD case, the abnormal protein was also seen
      in the pons and medulla oblongata. The brain in the ALS-FTD case presented Abeta
      and AT8 positivity in the hippocampus and entorhinal cortex (Braak I and II).
      DISCUSSION: The hypothesis supported by scientific literature that these
      neurodegenerative diseases can have the same etiology with distinct encephalic
      region involvement is corroborated by the present study.

PMID- 29213522
TI  - Memory specificity training can improve working and prospective memory in
      amnestic mild cognitive impairment.
AB  - : Amnestic Mild Cognitive Impairment (MCI) is one of the cognitive profiles of
      aging. OBJECTIVE: In this study, Memory Specificity Training (MEST) was used as
      cognitive training in patients with amnestic MCI to understand the effectiveness
      of the intervention on memory dimensions. METHODS: Twenty patients that met the
      criteria for amnestic MCI were selected and randomly assigned to experimental
      (n=10) or control (n=10) groups. The experimental group received five sessions of
      training on memory specificity while the participants in the control group took
      part in two general placebo sessions. Participants were assessed before,
      immediately after, and three months after, the treatment using the
      Autobiographical Memory Test, the Prospective and Retrospective Memory
      Questionnaire, the Wechsler Memory Scale, and the Hospital Anxiety and Depression
      Scale. Analysis of variance was used to analyze the data. RESULTS: Results from
      both post-test and follow-up treatment indicated that MEST improves working and
      prospective memory (p<0.05). CONCLUSION: These findings support the effectiveness
      of MEST for MCI patients as a viable cognitive intervention. Also, the findings
      have implications for the role of brain plasticity in the effectiveness of this
      intervention.

PMID- 29213523
TI  - Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of
      Bogota.
AB  - : The low prevalence of dementia described in communities is likely due to the
      low sensitivity of screening tests and an absence of evaluation by specialists.
      OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and
      dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional
      study was conducted by specialists to evaluate cognition and associated
      demographic risk factors in 1,235 independent community-dwelling adults from
      Bogota. In Phase I, screening was performed using the MMSE and MoCA tests. In
      Phase II, after application of a comprehensive neuropsychological battery with
      neurologic and psychiatric evaluations, a cognitive diagnosis was established by
      consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was
      23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45),
      and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI
      cases were amnestic. Dementia was associated with incomplete primary education,
      OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70
      10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION:
      The prevalence of dementia found was greater than the rates reported in previous
      studies. Low educational level was the main risk factor for cognitive impairment
      and should be considered in strategic planning for the local health system.

PMID- 29213524
TI  - Delirium in the elderly: A systematic review of pharmacological and non
      pharmacological treatments.
AB  - : Delirium is a common disorder associated with poor prognosis, especially in the
      elderly. The impact of different treatment approaches for delirium on
      morbimortality and long-term welfare is not completely understood. OBJECTIVE: To
      determine the efficacy of pharmacological and non-pharmacological treatments in
      elderly patients with delirium. METHODS: This systematic review compared
      pharmacological and non-pharmacological treatments in patients over 60 years old
      with delirium. Databases used were: MEDLINE (PubMed), EMBASE, Cochrane CENTRAL
      and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles
      were selected. The six non-pharmacological intervention studies showed no impact
      on duration of delirium, mortality or institutionalization, but a decrease in
      severity of delirium and improvement in medium-term cognitive function were
      observed. The most commonly used interventions were temporal-spatial orientation,
      orientation to self and others, early mobilization and sleep hygiene. The four
      studies with pharmacological interventions found that rivastigmine reduced the
      duration of delirium, improved cognitive function and reduced caregiver burden;
      olanzapine and haloperidol decreased the severity of delirium; droperidol reduced
      length of hospitalization and improved delirium remission rate. CONCLUSION:
      Although the pharmacological approach has been used in the treatment of delirium
      among elderly, there have been few studies assessing its efficacy, involving a
      small number of patients. However, the improvements in delirium duration and
      severity suggest these drugs are effective in treating the condition. Once
      delirium has developed, non-pharmacological treatment seems less effective in
      controlling symptoms, and there is a lack of studies describing different non
      pharmacological interventions.

PMID- 29213525
TI  - Motor learning characterization in people with autism spectrum disorder: A
      systematic review.
AB  - : Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder primarily
      characterized by deficits in social interaction, communication and implicit skill
      learning. OBJECTIVE: To analyse the results of research on "motor learning" and
      the means used for measuring "autistic disorder". METHODS: A systematic
      literature search was done using Medline/PubMed, Web of Science, BVS (virtual
      health library), and PsycINFO. We included articles that contained the keywords
      "autism" and "motor learning". The variables considered were the methodological
      aspects; results presented, and the methodological quality of the studies.
      RESULTS: A total of 42 studies were identified; 33 articles were excluded because
      they did not meet the inclusion criteria. Data were extracted from nine eligible
      studies and summarized. CONCLUSION: We concluded that although individuals with
      ASD showed performance difficulties in different memory and motor learning tasks,
      acquisition of skills still takes place in this population; however, this skill
      acquisition is related to heterogeneous events, occurring without the awareness
      of the individual.

PMID- 29213526
TI  - Mini-mental state exam for children (MMC) in children with hemiplegic cerebral
      palsy.
AB  - : Cognitive impairment is frequent in cerebral palsy (CP) and there is a lack of
      multiprofessional screening instruments. OBJECTIVE: The aim of this study was to
      investigate the utility of the Mini-Mental State Examination for Children (MMC),
      an adapted version of the Mini-Mental State Examination, in screening for
      cognitive impairments in children with CP. METHODS: We assessed 397 Brazilian
      children, 310 with typical development and 87 with CP (hemiplegic and
      quadriplegic forms), aged 5-16 years. Association between the MMC and general
      intelligence was assessed by the Colored Progressive Matrices instrument.
      RESULTS: Psychometric indexes for the MMC were adequate. ROC analyses revealed
      effective diagnostic accuracy in all ages assessed. Cut-off values are reported.
      Major difficulties on the MMC were observed in children with CP, particularly
      individuals with the quadriplegic form. Moreover, the MMC showed moderate
      correlation with the intelligence test, and was reliable in discriminating, among
      clinical cases, those with poorer cognitive abilities. CONCLUSION: The MMC could
      be useful as a multiprofessional screening instrument for cognitive impairment in
      children with hemiplegic CP. Results of the MMC in quadriplegic CP children
      should be interpreted with caution. Diagnosis should be confirmed by further
      psychological testing.

PMID- 29213527
TI  - High education accelerates cognitive decline in dementia: A brief report from the
      population-based NEDICES cohort.
AB  - : High education has been associated with faster cognitive decline after
      diagnosis of Alzheimer's disease (AD), but it is unclear whether these findings
      extend to other dementia subtypes. OBJECTIVE: We investigated whether educational
      attainment influences the cognitive trajectories of older adults with different
      dementia subtypes. METHODS: All participants were selected from NEDICES, a
      prospective population-based cohort study of Spanish older adults. A total sample
      of 53 individuals with dementia completed the MMSE-37 at Times 1 and 2 (mean
      follow-up=2.8+/-0.5 years) to assess cognitive decline. RESULTS: At follow-up,
      MMSE-37 scores had decreased by 3.34+/-4.98 points in low-educated individuals
      with dementia versus 7.90+/-4.88 points in high-educated subjects (effect size
      (r)=0.32, p=0.02). CONCLUSION: Educational level influenced the cognitive
      trajectories of patients with dementia assessed by the MMSE-37.

PMID- 29213528
TI  - Francisco de Castro: Localizationism, intelligence and the frontal lobe.
AB  - This article addresses the largely unknown legacy of Francisco de Castro
      regarding the neurological sciences. His essay "Psychogenic Cortical Centers",
      written in 1881 for his admission to the Imperial Academy of Medicine in Rio de
      Janeiro, is a refined appreciation of the theory of localized cortical functions
      that was in evidence in Europe in the second half of the nineteenth century.

PMID- 29213529
TI  - Therapeutic effect of transcranial direct current stimulation on
      neuropsychological symptoms of an elderly patient: A case report.
AB  - Although growing evidence points to the potential therapeutic effects of
      transcranial Direct Current Stimulation (tDCS), there is still no consensus on
      the most appropriate protocol to be used in specific neurological and
      neuropsychological symptoms. This case report evaluated the neuromodulatory
      therapeutic effects of two 15-day courses of tDCS on an elderly female patient,
      aged 78 years with mild neurocognitive disorder, chronic pain and depression
      related symptoms. Results indicated an overall significant improvement of
      cognitive and executive functions, as well as reduction in both depression and
      chronic pain symptoms. These results highlight the potential of tDCS as a safe
      and useful neuromodulatory clinical tool in the rehabilitation of elderly
      patients.

PMID- 29213531
TI  - Dementia & Neuropsychologia: one year on.

PMID- 29213530
TI  - Disease awareness may increase risk of suicide in young onset dementia: A case
      report.
AB  - Studies report that people with young onset Alzheimer's disease (YOAD) have
      higher levels of disease awareness compared to those with late onset AD. We
      report a case of a man with YOAD who had preserved awareness of disease,
      depression and risk of suicide associated with the development of the dementia.
      Cognitive functioning, disease severity, depressive symptoms and awareness of
      disease were assessed using validated measures. The person with YOAD showed a
      moderate level of disease severity and high degree of dependence for activities
      of daily living. There was recognition of memory problems and routine changes
      with presence of intense pessimism, low self-esteem and suicidal ideation. This
      case points to the existence of specific issues related to young onset dementia
      and the clinical importance of identifying and treating patients who might be
      aware of their condition.

PMID- 29213533
TI  - qEEG spectral peak in Alzheimer's disease: A possible tool for treatment follow
      up.
AB  - : qEEG spectral analysis has been considered highly sensitive to cortical
      functional changes and agrees strongly with the clinical diagnosis of AD. The
      sensitivity of spectral analysis has ranged from 71% to 81% in several studies.1
      3. Objective: The aim of this study was to retrospectively evaluate whether alpha
      qEEG spectral peak can supplement clinical examination by constituting an
      independent tool to monitor treatment and follow-up of dementia progression in
      Alzheimer's disease (AD). In addition, we examined the demographic data and alpha
      power spectra distribution of patients and elderly normal controls. Methods:
      qEEGs were selected from 2 groups of patients: normal controls (n=30), and
      patients who fulfilled criteria for mild probable AD diagnosis (n=41). The alpha
      qEEG spectral analysis and MMSE were performed once or twice a year. Results: In
      our groups, MMSE scores and qEEG alpha spectral peak were unchanged (no
      statistical differences) after anticholinesterase use where qEEG spectral peak
      was never lower than 8 Hz in the control group. Conclusion: This study supports
      two important concepts. First, 8 Hz alpha appears to be the lowest awake spectral
      peak compatible with normality. And finally, in a clinical context, qEEG is a
      valuable diagnostic tool that could prove useful for Dementia follow-up.

PMID- 29213532
TI  - Peripheral biomarkers of oxidative stress in aging and Alzheimer's disease.
AB  - Aging is associated with a greatly increased incidence of a number of
      neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's
      disease (PD) and amyotrophic lateral sclerosis (ALS). These conditions are
      associated with chronic inflammation, which generates oxygen reactive species,
      ultimately responsible for a process known as oxidative stress. It is well
      established that this process is the culprit of neurodegeneration, and there are
      also mounting evidences that it is not restricted to the central nervous system.
      Indeed, several studies, including some by our group, have demonstrated that
      increased peripheral oxidative stress markers are associated to aging and, more
      specifically, to AD. Therefore, it is very instigating to regard aging and AD as
      systemic conditions that might be determined by studying peripheral markers of
      oxidative stress.

PMID- 29213534
TI  - A new Brief computerized cognitive screening battery (CompCogs) for early
      diagnosis of Alzheimer's disease.
AB  - : Screening tests for early diagnosis of dementia are of great clinical
      relevance. The ideal test set must be brief and reliable, and should probe
      cognitive components impaired in Alzheimer's disease (AD). Objectives: To develop
      a new Computerized Cognitive Screening test (CompCogs), and to investigate its
      validity for the early diagnosis of AD, and evaluate its heuristic value in
      understanding the processing of information in AD. Methods: The computerized
      neuropsychological performance battery, originally including six tests, was
      applied in forty seven patients with probable mild AD and 97 controls matched for
      age and education. This computerized neuropsychological test battery, developed
      with MEL Professional, allows control of timing and order of stimuli
      presentation, as well as recording of response type and latency. A brief
      screening version, CompCogs, was selected using the most discriminative
      neuropsychological test variables derived from logistic regression analysis. Full
      battery administration lasted about 40 minutes, while the CompCogs took only 15
      minutes. Results: CompCogs included the Face test (correct response) and Word and
      Forms with Short term memory tests (reaction time). CompCogs presented 91.8%
      sensitivity and 93.6% specificity for the diagnosis of AD using ROC analyses of
      AD diagnosis probability derived by logistic regression. Conclusions: CompCogs
      showed high validity for AD early diagnosis and, therefore, may be a useful
      alternative screening instrument.

PMID- 29213535
TI  - Standardization of the normative group for the third version of the test of
      visual attention - TAVIS.
AB  - : Despite the importance of objective measures of attention to clinical practice,
      there is a paucity of Brazilian standardized tests. Objective: The aim of the
      present study was the standardization of a normative group for the third version
      of a computerized test of visual attention (TAVIS-3), developed to evaluate
      children and adolescents in the 6 to 17 years age range. Methods: 631 students
      from 3 schools in Rio de Janeiro city were assessed with TAVIS-3, administered by
      experienced psychologists, following parents' authorization. Results: The
      normative groups were determined considering performance of different age groups:
      from 6 to 10 years (with scores for 5 different ages); from 11 to 12 and from 13
      to 17 years. Three tasks (focused, shifted and sustained attention) were
      standardized for each age group. Conclusion: The standardization of a normative
      group for TAVIS-3 discriminated performance ranges for distinct age groups,
      allowing its use as a neuropsychological assessment of attention.

PMID- 29213536
TI  - Planning abilities of children aged 4 years and 9 months to 8 1/2 years: Effects
      of age, fluid intelligence and school type on performance in the Tower of London
      test.
AB  - : The present study investigated the relationship between age and one type of
      environmental factor, namely, type of school (i.e., private vs. public), and the
      development of mental planning ability, as measured by the Tower of London (TOL)
      test. Methods: Participants comprised 197 public and 174 private school students,
      ranging in age from 4 years and 9 months to 8 years and 6 months. Besides the TOL
      test, students were administered Raven's Colored Matrices. Results: Results
      confirmed the findings of previous studies that both age and school type are
      important predictors of mental planning. Furthermore, results also suggest that
      the relationship between type of school and mental planning ability cannot be
      accounted for by differences in students' fluid intelligence. Conclusion: In the
      present study, the TOL test continued to differentiate public from private school
      students, even after we controlled for the effect of differences on the Raven
      test.

PMID- 29213537
TI  - Functional communication ability in frontotemporal lobar degeneration and
      Alzheimer's disease.
AB  - : Functional communication is crucial for independent and efficient communicative
      behavior in response to every day activities. In the course of dementia
      progression, cognitive losses may impair these abilities. For this reason,
      functional communication assessment should be part of a formal assessment to
      quantify and qualify the impact of deficiency on patients' lives. Objective: To
      compare functional communication abilities in fronto-temporal lobar degeneration
      (FLTD) and Alzheimer's disease (AD). Methods: Six AD patients (mean age: 82.50+/
      2.66 years; mean education: 5.67+/-3.61 years), and eight FTLD patients (mean
      age: 57.13+/-9.63 years; mean education: 10.86+/-6.91 years) had their close
      relatives answer the Functional Assessment of Communication Skills for Adults
      (Asha-facs) . Statistical analyses correlated the performance on each of the Asha
      facs domains (social communication, communication of basic needs; reading,
      writing, number concept and daily planning) between both groups. Results:
      Analyses showed that functional communication was similar for AD and FTLD
      patients. Only two items had statistical difference, namely 'Comprehension of
      inference' (AD 6.7+/-1.33; FTLD 2.43+/-2.30, p=0.017) and 'capacity to make basic
      money transactions' (AD 2.17+/-2.04; FTLD 4.00+/-0.90, p=0.044). Comparison among
      the four domains' mean scores revealed no significant difference. Conclusion: The
      Asha-facs is a useful instrument to characterize functional communication
      abilities in both FTLD and AD. Nevertheless, the analysis presented for this
      sample showed that the Asha-facs could not discriminate which aspects of the FTLD
      and AD differed.

PMID- 29213538
TI  - Hippocampal atrophy and verbal episodic memory performance in amnestic mild
      cognitive impairment and mild Alzheimer's disease: A preliminary study.
AB  - : To evaluate hippocampal volume in patients with AD and aMCI, and correlate its
      atrophy with verbal episodic memory performance. Methods: We studied 42
      individuals older than 50 years, including 14 with amnestic mild cognitive
      impairment (aMCI), 14 with mild Alzheimer's disease (AD) and 14 normal controls.
      All individuals were submitted to the Rey auditory verbal learning test (RAVLT)
      to evaluate episodic memory. They were also submitted to the forward (FDS) and
      backward digit span (BDS) subtest of WAIS-R to evaluate working memory and
      attention, and to the Mini Mental State Examination (MMSE). Hippocampal
      volumetric measurements were performed according to anatomic guidelines from a
      standard protocol using high-resolution T1-inversion recovery 3-mm coronal MRI
      slices. Hippocampal volumes (HV) were corrected for the variation in total
      intracranial volume. There was no significant difference between the three groups
      concerning age and education. Results: On RAVLT, there was a continuum between
      the three groups, with AD recalling less words, controls more, and aMCI subjects
      showing an intermediate performance on all sub-items. We found an asymmetry
      between HVs, with smaller mean left HV for all groups. ANOVA and post hoc Tukey's
      test for comparisons of HV showed a significant difference among groups, with
      difference between controls and both AD and aMCI, although there was no
      significant difference between AD and aMCI groups. Conclusions: There was a
      significant correlation between hippocampal volumes and scores on RAVLT,
      confirming that medial temporal structures are closely associated with memory
      performance in normal ageing as well as in aMCI and AD.

PMID- 29213539
TI  - Subjective memory complaints and cognitive performance in a sample of healthy
      elderly.
AB  - : Memory loss is a major complaint among the elderly population. However, the
      clinical significance of this symptom is variable and also controversial in the
      scientific literature. Objective: To compare the cognitive performance of two
      groups of healthy elderly, one group with and the other without, subjective
      memory complaints (SMC). Methods: Sixty cognitively intact elderly individuals
      (39 females and 21 males), aged 69.9+/-6.3 years and with educational level of
      8.5+/-5.5 years, were included in the study. Participants were submitted to the
      Mini-Mental State Examination and to the Cornell depression scale in order to
      rule out global cognitive impairment and depression, respectively. Moreover, they
      answered the MAC-Q, a questionnaire devised to evaluate subjective impression of
      memory function. Subsequently, they were submitted to the digit span forward and
      backward, the Brief Cognitive Screening Battery, and to the Frontal Assessment
      Battery. Results: Twenty-seven individuals had MAC-Q scores <25 and thus were
      classified as not having SMC, while 33 had MAC-Q scores >=25 and were considered
      to have SMC. No differences for age, gender, education and MMSE scores were found
      between the two groups. The comparison between the performance of the groups of
      complainers and non-complainers on the different cognitive tests yielded no
      significant difference, although there was a trend toward non-complainers
      performing better on incidental memory. Conclusions: The presence of SMC was not
      associated to objective memory impairment or to other cognitive deficits in this
      group of elderly individuals.

PMID- 29213540
TI  - Cognitive complaints compared to performance on a mental state screening test in
      elderly outpatients.
AB  - : Memory and other cognitive complaints are common in the elderly population.
      However, the clinical meaning of these complaints remains controversial.
      Objectives: The goal of this study was to investigate the association between
      cognitive complaints and performance on a mental state screening test in elderly
      patients attended for the first time at the Neurogeriatric and Dementia (NGA)
      Outpatient Clinic within a major University hospital. Methods: Two hundred
      patients referred to the NGA Clinic during 2005, 2006 and 2007 first semesters
      participated in the study. The variables of interest were:(a) source of and
      reason for referral;(b) whether or not they had previously been evaluated with
      the screening test (Mini Mental State Exam - MMSE) by their physicians before
      referral to our specialized clinic;(c) cognitive complaints; and(d) performance
      on the screening test (MMSE) at the NGA Clinic. Results: The main reason for
      referral to the NGA clinic was cognitive complaints 63% (N=126), where only 5%
      (N=10) of the referred patients had been previously evaluated by the cognitive
      screening test (MMSE or equivalent). Of the 135 patients who presented cognitive
      complaints during the first appointment, 52 (38%) presented MMSE scores below the
      education-adjusted cut-off. No association between cognitive complaint and
      performance on the MMSE during the first evaluation at the NGA Clinic was
      observed (chi2=3.04, p=0.1). Conclusions: Although cognitive complaints among
      elders should not be disregarded, the mental state screening evaluation is
      crucial for the detection of clinically significant cognitive impairment.

PMID- 29213541
TI  - Assessment of memory complainers in Sao Paulo, Brazil: Three-year results of a
      memory clinic.
AB  - : Memory clinics were established in the USA and European countries as services
      to attend patients who complain of cognitive deficits, referred by primary care
      doctors, specialists and other hospitals. Objective: We aimed to describe the
      clinical and cognitive profile of consecutively evaluated subjects during the
      initial three years of service of a memory clinic from a university hospital.
      Methods: Subjects were submitted to a clinical work-up for dementia, which
      included laboratory exams, cranial computerized tomography, cognitive tests, and
      a comprehensive neuropsychological battery. Diagnosis was made according to ICD
      10 criteria. Results: We evaluated 104 subjects (67.3% females and 32.7% males),
      with mean age of 59.1 years, 88.8% aged 50 years or above. Mean schooling was 9.9
      years. Patients were classified into 10 different primary diagnostic categories,
      namely Depression (26.9%), Alzheimer's disease (17.3%), Memory complaints without
      objective impairment (17.3%), Mild Cognitive Disorder - MCD (14.4%), and Anxiety
      (12.5%) the most frequent diagnosis. Comparing patients with dementia, MCD,
      Depression or Anxiety and Memory complainers, by age (below and above 60 years),
      dementia was more commonly diagnosed in older subjects, while a higher frequency
      of memory complainers was found in the younger group. Conclusions: This
      preliminary report from an outpatient group of referred patients with cognitive
      complaints showed a higher frequency of psychiatric disorders in this sample. The
      memory clinic approach should be considered as a model of service which can
      evaluate subjects with cognitive complaints effectively and improve the quality
      of care delivered to this patient group.

PMID- 29213542
TI  - Involution of categorical thinking processes in Alzheimer's disease: Preliminary
      results.
AB  - : Alzheimer's disease (AD) is a degenerative brain disorder characterized by
      progressive losses in cognitive functions, including memory. The sequence of
      these losses may correspond to the inverse order of the normal sequence of
      ontogenetic cognitive acquisitions, a process named retrogenesis. One of the
      acquisitions that improve in normal development is the ability to retrieve
      previously acquired categorical knowledge from semantic memory in order to guide
      associative thinking and memory processes; consequently, children become able to
      associate verbal stimuli in more complex taxonomic ways and to use this knowledge
      to improve their recall. Objective: In this study, we investigated if AD-related
      deterioration of semantic memory involves a decrease in categorical thinking
      processes with progression of the disease, according to the retrogenesis
      hypothesis. Methods: We compared the performance of AD patients at mild and
      moderate stages, and of groups of 7, 10 and 14-year-old children in tasks of free
      association along with recall tasks of perceptually and semantically related
      stimuli. Results: ANOVAS showed a decrease in taxonomic associations and an
      increase in diffuse associations between mild and moderate stages, corresponding
      to the inverse order shown by the child groups. At the moderate AD stage, the
      pattern was similar to that of 7-year-old children. Both groups of patients
      performed worse than child groups in recall tasks. Conclusions: These results
      corroborate the hypothesis of an involution of the processes of categorical
      associative thinking in the course of the disease.

PMID- 29213543
TI  - Professionally successful adults with attention-deficit/hyperactivity disorder
      (ADHD): Compensation strategies and subjective effects of pharmacological
      treatment.
AB  - : Although as a group, adult patients with ADHD have difficulties in social
      functioning due to inattention and executive dysfunction, some strive and succeed
      in living a productive, independent life. Purpose: To report on professionally
      successful adults with ADHD and analyze their main symptoms, compensation
      strategies and the subjective effect of methylphenidate on their functioning.
      Methods: The main symptoms of five patients with ADHD who are University educated
      and financially independent are reported. These patients were selected from a
      personally followed cohort of adults with ADHD. All were diagnosed according to
      DSM-IV adapted criteria (K-SADS E, version 6.0) and completed the Portuguese
      translated version of the ADHD adult self-reporting scale (ASRS). Results: Main
      reported symptoms included difficulties with attention, tendency to procrastinate
      and to 'shuffle' priorities, excessive daytime somnolence, memory difficulties
      and impulsiveness. Compensation strategies revolve around conscious, 'energy
      demanding' and time consuming efforts to control and circumvent symptomatic
      behavioral tendencies. They feel methylphenidate helps by alleviating the need to
      constantly apply compensation strategies for socially disabling symptoms. In sum,
      they achieve the same results in a more natural, less effortful fashion.
      Conclusions: Adults with ADHD may succeed professionally despite significant
      symptoms of inattention and executive dysfunction. They do so by appropriately
      using effortful strategies of compensation, the need for which is alleviated by
      the use of methylphenidate. These subjective reports require confirmation in
      prospective studies on larger series of patients.

PMID- 29213544
TI  - Clozapine for severe ("kraepelinian") schizophrenia: Sustained improvement over 5
      years.
AB  - : Clozapine has become a keystone in the treatment of schizophrenia because of
      its efficacy as an antipsychotic with negligible neuroleptic effects. The long
      term stability of its effects, however, is poorly understood, because most
      studies have probed the usefulness of clozapine over a period of weeks to several
      months at the most. Knowing whether clozapine's benefits are sustained over the
      very long-term, i.e., more than 5 years, may be critical for cost-benefit
      analyses. Objective: To report the results of an open study on the efficacy of
      clozapine over the very long-term. Methods: Thirty-three adults (26 men) with
      severe (kraepelinian) schizophrenia were assessed at regular intervals using a
      brief neuropsychiatric battery over a 5-year period. Results: A significant
      improvement was observed between the pre-clozapine and the first "on-clozapine"
      evaluation. This improvement was paralleled by a remarkable conversion of
      schizophrenia from "active" (mostly paranoid) into "residual" in 70% of all
      patients. Eight patients became functionally productive to the point of being
      capable of living an independent life. Roughly one-third of our cases showed no
      improvement. Conclusions: Clozapine is a safe and effective drug for patients
      with severe schizophrenia who have failed to improve on other antipsychotic
      drugs. Clozapine's maximal benefit is established by the end of the first year of
      treatment and continues unabated for many years thereafter. Clozapine-resistant
      patients remain a major challenge calling for the discovery of new treatments for
      schizophrenia.

PMID- 29213546
TI  - Competition for clinical cases in Alzheimer's disease (CCCAD) - Janssen-Cilag.

PMID- 29213545
TI  - Dysexecutive mild cognitive impairment associated to frontal atrophy: Case
      report.
AB  - Non-amnestic mild cognitive impairment (MCI) evolving to neurodegenerative
      diseases other than Alzheimer's disease (AD) is rarely well documented. We report
      a case of a 49 year-old woman who presented a slowly progressive
      attentional/dysexecutive syndrome sparing other cognitive domains and without
      significant impairment of daily life activities. Her mother had Parkinsonism and
      her brother, a psychotic syndrome. Brain CT/MRI showed frontal atrophy while
      brain SPECT showed moderate cortical hypoperfusion, mainly in the frontal lobes.
      Our case is an example of non-memory MCI whose neuropsychological data and brain
      imaging indicating high likelihood of progression to a non-AD dementia.

PMID- 29213547
TI  - Trends of the journal: letters, reviews, abstracts, and manuscripts from abroad.

PMID- 29213548
TI  - Subcortical ischemic vascular disease and cognition: A systematic review.
AB  - : Subcortical Ischemic Vascular Disease (SIVD) is underdiagnosed. This review
      investigates the relationship among SIVD severity, cognitive status and
      neuroimaging markers. Methods: Cohort, cross-sectional and case control studies
      were searched on ISI, Medline, Scielo, PsychoInfo and LILACS databases published
      between 1995 and 2006. Results: The most impaired cognitive domains were
      executive, attentional and memory retrieval mechanisms. These cognitive features
      were frequently associated to White Matter Lesions (WML). Conclusions: WML is an
      independent factor in cognitive decline. However, the threshold for this impact
      is not yet clearly established.

PMID- 29213549
TI  - Neuropsychological alterations in mercury intoxication persist several years
      after exposure.
AB  - : Elemental mercury is a liquid toxic metal widely used in industry. Occupational
      exposure occurs mainly via inhalation. Previously, neuropsychological assessment
      detected deficits in former workers of a fluorescent lamp plant who had been
      exposed to elemental mercury vapor and were away from exposure for several years
      at the time of examination. Objectives: The purpose of this work was to reexamine
      these functions after 18 months in order to evaluate their progression. Methods:
      Thirteen participants completed tests of attention, inhibitory control,
      verbal/visual memory, psychomotor speed, verbal fluency, visuomotor ability,
      executive function, semantic knowledge, and depression and anxiety inventories on
      2 separate occasions. Results: At baseline, the former workers indicated slower
      psychomotor and information processing speed, verbal spontaneous recall memory
      impairment, and increased depression and anxiety symptoms compared to controls
      (P<0.05). Paired comparisons of neuropsychological functioning within the exposed
      group at baseline and 1.5 years later showed poorer immediate memory performance
      (P<0.05). There were no differences on other measures. Conclusions: Although the
      literature show signs of recovery of functions, the neuropsychological effects
      related to mercury exposure are found to persist for many years.

PMID- 29213550
TI  - Dementia and functional decline in patients with Parkinson's disease.
AB  - : Functional decline in Parkinson's disease (PD), characterized by reduced
      ability to carry out activities of daily living, usually results from typical
      motor impairment and may be aggravated by concomitant cognitive impairment.
      Objective: To compare the functional decline in Parkinson's disease between
      patients with dementia and cognitively preserved patients. Methods: From an
      original sample composed of 50 patients with a clinical diagnosis of idiopathic
      PD seen in a consecutive series, 33 non-depressed patients were selected
      comprising 13 with dementia and 20 cognitively preserved individuals. All
      patients enrolled in this study were drawn from a public outpatient clinic,
      specialized in movement disorders. The clinical stage of PD was determined by the
      Hoehn & Yahr scale, and the functional capacity was verified using the Unified
      Parkinson's Disease Rating Scale UPDRS ADL (subscale II: activities of daily
      living) and the Schwab & England scale. The two last scales measure the
      functional degree of independence in activities of daily living. The
      neuropsychological assessment was performed using The Cambridge Examination for
      Mental Disorders of the Elderly - CAMCOG, Cognitive Section and the Stroop Color
      Word Test. Results: As expected, in comparison with cognitively preserved
      patients, the group with dementia presented significantly lower scores throughout
      the neuropsychological evaluation. The patients with dementia were found to have
      a longer period of disease, a more advanced clinical staging according to the
      Hoehn & Yahr, and greater functional decline according both to the UPDRS ADL and
      Schwab & England, with statistically significant difference between the groups.
      Conclusion: Patients with dementia were at a more advanced clinical stage of
      Parkinson's disease and evidenced greater functional decline in comparison with
      patients without dementia.

PMID- 29213551
TI  - The Cambridge Behavioural Inventory revised.
AB  - : Neurobehavioural and psychiatric symptoms are common in a range of
      neurodegenerative disorders with distinct profiles which are helpful in the
      diagnosis and monitoring of these disorders. The Cambridge Behavioural Inventory
      (CBI) has been shown to distinguish frontotemporal dementia (FTD), Alzheimer's
      disease (AD), Huntington's disease (HD) and Parkinson's disease (PD), but it is
      lengthy. Objective: To develop a shorter version of the 81 item CBI. Methods: CBI
      data from 450 participants with behavioural variant frontotemporal dementia (bv
      FTD) (64), AD (96), PD (215) and HD (75) were analysed using Principal Components
      Analysis and measures of internal consistency (Cronbach alpha). Results: A
      reduced 45-item questionnaire was developed. The instrument identified distinct
      behavioural profiles and performed as well as the original version. Conclusions:
      A shorter (45 item) version of the CBI is capable of differentiating bv-FTD and
      AD from PD and HD. It may be useful in delineating the type and extent of
      problems in these disorders as well as monitoring therapeutic interventions.

PMID- 29213552
TI  - Behavioral and activities of daily living inventories in the diagnosis of
      frontotemporal lobar degeneration and Alzheimer's disease.
AB  - : The differential diagnosis between frontotemporal lobar degeneration (FTLD) and
      Alzheimer's disease (AD) is often challenging. Objectives: To verify the
      usefulness of behavioral and activities of daily living inventories in the
      differential diagnosis between FTLD and AD. Methods: Caregivers of 12 patients
      with FTLD (nine with frontotemporal dementia, two with semantic dementia and one
      with progressive non-fluent aphasia) and of 12 patients with probable AD were
      interviewed. The Brazilian version of the Frontal Behavioral Inventory (FBI) and
      Disability Assessment for Dementia (DAD ) were used. Results: The mean of the
      MMSE score was 12.4+/-10.7for patients with FTLD and 11.9+/-6.2for patients with
      AD (p=0.93). Mean scores on the DAD were 33.7+/-27.7in patients with FTLD and
      55.6+/-29.7in patients with AD (p=0.06), while for the FBI they were 42.6+/
      10.0for FTLD and 16.7+/-11.7for AD (p<0.01). Conclusions: In this study, FBI was
      found to be a helpful tool for the differential diagnosis between FTLD and AD.
      Although the DAD was not useful in differential diagnosis in our sample we
      believe it to be important for measuring the severity of the disease through
      quantitative and qualitative assessment of functional deficits of the patients.

PMID- 29213553
TI  - Influence of age, gender and educational level on performance in the Brief
      Cognitive Battery-Edu.
AB  - : The Brief Cognitive Battery-Edu (BCB-Edu) contains nine tests, seven of which
      are related to the memory of drawings, and has good accuracy in the diagnosis of
      cognitive impairment. Objectives: To evaluate the influence of age, gender and
      educational level on the performance in tests related to memory of drawings of
      the BCB-Edu in healthy subjects. Methods: Participants were adult volunteers;
      exclusion criteria were illiteracy, neurologic or psychiatric disorders, visual
      or hearing impairment, untreated chronic clinical conditions, alcoholism, use of
      drugs, and for those aged 65 or over, an informant report of cognitive or
      functional impairment. We evaluated 325 individuals (207 women), with a mean age
      of 47.1 (+/-16.8) years, ranging from 19 to 81, and a mean of 9.8 (+/-5.0)
      schooling-years. Univariate analyses, correlations and logistic regression were
      employed (alpha=0.05). Results: There were significant negative correlations
      between age and the scores in four of the seven tests. However, schooling-years
      were positively correlated to the scores, where schooling-years decreased with
      age in this sample (rho= -0.323; p<0.001). Logistic regression confirmed that
      gender influenced the learning of drawings, where women performed better, while
      age influenced incidental memory, immediate memory, learning and delayed recall
      of the drawings, and schooling-years influenced visual identification, immediate
      memory, learning, delayed recall and recognition of the drawings. Conclusion:
      Gender, age and education influence the performance on the memory of drawings of
      the BCB-Edu, although the extent of these influences differs according to the
      nature of the test.

PMID- 29213554
TI  - General psychiatric or depressive symptoms were not predictive for mortality in a
      healthy elderly cohort in Southern Brazil.
AB  - : General psychiatric symptoms may interfere with the ability of individuals to
      take care of their health, to get involved with activities and develop social
      abilities, thereby increasing risk of death. Objective: To evaluate general
      psychiatric symptoms as predictive factors for mortality in a community elderly
      cohort in Southern Brazil. Methods: 345 healthy elderly, aged .60 years, from the
      catchment area of Hospital de Clinicas de Porto Alegre were followed from 1996.
      Data for the present study were drawn from the period 1996-2004. General
      psychiatric symptoms (Self-Reporting Questionnaire . SRQ), depressive symptoms
      (Montgomery-Asberg depressive rating scale), and Mini Mental State Examination
      scores at baseline were included in the study. Socio-demographic, medical
      conditions, and functional capacity were also analyzed. The outcome was vital
      status at follow-up obtained from family members, hospital records and checked
      against official death registers. Results: Of the 345 baseline individuals, 246
      were followed-up. The global mortality rate over the study period was 36.9%
      (N=90). Those who deceased during the period were older (73.5+/-7.5), more
      dependent overall, and more cognitively impaired than the living elderly
      (univariate analyses). In the logistic regression, only age (OR=0.93; p=0.003)
      and functional capacity (OR=0.22; p=0.007) remained significant in the final
      equation. Conclusion: Psychiatric symptoms presented no association with
      mortality in the present sample. Older age and functional incapacity were risk
      factors for mortality.

PMID- 29213555
TI  - Effect of schooling in auditory lexical decision.
AB  - : The task of lexical decision demands the functioning of the phonological loop
      to identify and discriminate strings of sounds and lexical knowledge to identify
      if this string can be taken as a real word or pseudo-word. Objective: To verify
      the effect of schooling on the performance of healthy elderly in lexical decision
      tasks, in the auditory modality. Methods: 23 Participants, aged sixty years or
      older were divided into two groups: 1-8 years and greater than 8 years of
      schooling. The PALPA lexical decision subtest containing words and pseudo-words
      was applied. Results: There was no significant difference between the groups in
      identifying words and pseudo-words. Errors in pseudo-words predominated in both
      groups. Total scoring of the groups differed with worse performance in the group
      with less schooling. There was a tendency toward statistically significant
      difference. The errors in words occurred predominantly in words of low
      imageability, especially in the lower educated group. In this group, there was a
      positive correlation between schooling and errors in pseudo-words. Conclusion:
      There was a mild effect of schooling in this task. Studies on lexical decision
      with larger samples could offer an important contribution for estimating pre
      morbid skills and contribute to understanding pathological conditions.

PMID- 29213556
TI  - Textual reading comprehension and naming in Alzheimer's disease patients.
AB  - : Among linguistic-cognitive failures, the retelling of stories and lexical
      disorders occur from the onset of AD. Recent studies have discussed whether
      lexical failures in AD patients include naming actions. Objectives: The aims of
      this study were to verify naming and reformulation of action difficulties in AD
      patients and their relationship with the retelling of stories. Our main questions
      were: Are there two linguistic abilities impaired in the early stages of AD? Is
      there some correlation between the capacity of naming actions and the retelling
      of stories? Methods: We assessed 28 elderly participants: 17 with probable AD and
      11 control subjects, with schooling >=4 years. The textual reading comprehension
      was measured using four stories with descriptive and narrative textual structure.
      The lexical production was verified by 17 actions on video, assessed by the
      participants' first and second verbal emissions. Results: The results showed that
      the retelling of stories is a task that discriminates patients with AD from
      healthy individuals. The naming and reformulation of actions tasks did not show
      significant differences among the patients and their controls. A positive
      correlation was found between the difficulties in retelling stories and the
      reformulation of the naming of actions. Conclusions: These results confirm
      previous findings that show the preservation of naming actions in patients with
      AD, which involve familiar actions, and that the retelling of short stories is an
      instrument that discriminates patients with AD from healthy elders. Results also
      suggest that the difficulties in retelling are related a breakdown in
      reformulating information, perhaps stemming from mechanisms of decreased memory
      work.

PMID- 29213557
TI  - Cognitive rehabilitation of neuropsychological deficits and mild cognitive
      impairment: a review of the literature.
AB  - : Neuropsychological rehabilitation is related to the treatment or optimization
      of disabilities, handicaps and cognitive deficiencies including emotional,
      behavioral and personality alterations, aiming at the best cognitive,
      neurobiological and social re-adaptation. Objective: The main aim of this paper
      is to review scientific studies published over the last five years on cognitive
      training with rehabilitation, focusing on elderly subjects with cognitive
      complaints and patients diagnosed with MCI. Methods: Data were generated from
      Medline, PsychoInfo and EMBASE including publications from 2002 to 2007 using the
      search terms "Mild Cognitive Impairment", "Cognitive Complaints",
      "Rehabilitation" and "Intervention Studies". Data collection criteria were
      restricted to the quality of evidence Class I. Results: Eight articles out of
      sixty eight previously selected were chosen because of their randomized studies,
      including techniques of cognitive rehabilitation in patients with cognitive
      complaints, MCI and neuropsychological training. Conclusions: The studies showing
      generalization of rehabilitation techniques to practical real life situations and
      use of an errorless learning approach were considered more effective in terms of
      maintaining treatment follow up, although further studies are recommended.

PMID- 29213559
TI  - Cognitive deficits associated with optic aphasia: Neuropsychological contribution
      to a differential diagnosis.
AB  - Optic aphasia is characterized by a deficit in naming objects presented visually,
      as a result of left occipito-temporal lesion. It differs from other
      neuropsychological disorders due to the nature of the deficits and impairment of
      cognitive function. A 52 year-old patient, admitted after an episode of sub-acute
      infarction in the territory of the left posterior cerebral artery involving the
      temporo-occipital region, was submitted to neuropsychological evaluation as part
      of a diagnostic investigation and presented specific characteristics of this
      disorder, as well as impairment to episodic memory. The relevance of the present
      case is justified not only due to the rarity of the disorder, but also because it
      highlights the importance of differential diagnosis in the treatment of patients.

PMID- 29213558
TI  - Neuropsychological rehabilitation program and behavioral disturbances in early
      stage Alzheimer patients.
AB  - : Alzheimer's disease (AD) is the most frequent cause of dementia and
      cholinesterase inhibitors are the available treatment in the mild stage. However
      cognitive rehabilitation has shown satisfactory results when combined with
      pharmacological treatment. Behavioral alteration is common in AD patients, which
      burdens caregivers and raises the risk of institutionalization. Providing
      caregivers guidance may enable them to assure better quality of life for patient
      and caregiver and lower institutionalization rates. Objective: To evaluate the
      effects of a neuropsychological rehabilitation program (NRP) combined with
      pharmacological treatment in early stage AD patients. Methods: We studied 12 AD
      patients (6 women), average age 75.42 (6.22) with 9.58 (5.6) years education in
      use of stable doses of cholinesterase inhibitors. Cognitive performance was
      evaluated using Mini-Mental State Examination (MMSE) and Alzheimer's Disease
      Assessment Scale-cognitive (ADAS-Cog). Caregivers responded to Neuropsychiatric
      Inventory (NPI) and Functional Activities Questionnaire (FAQ) at initial
      evaluation (T1), and after 8 months of rehabilitation program (T2). The program
      comprised two sessions every week and family guidance every fortnight. Results:
      MMSE (T1:23.25 (1.82)/T2:23.42 (2.81); ADAS-Cog (T1:17.11 (6.73)/T2:21.2 (8.59);
      NPI (T1:23.42 (23.38)/T2:19.83 (17.73); FAQ (T1:10.67 (7.24)/T2: 13.92 (6.92).
      Conclusions: These results show the importance of providing guidance and support
      for caretakers. Study limitations were the small number of patients and absence
      of a control group with only drug treatment to compare with combined
      pharmacological and rehabilitation treatments.

PMID- 29213561
TI  - Perspectives of the journal.

PMID- 29213560
TI  - Compulsory notification of prion diseases in Brazil: What has changed since 2005?

PMID- 29213562
TI  - Cognitive Neurology and Ageing Scientic Department of the Brazilian Academy of
      Neurology.

PMID- 29213563
TI  - 2009 International Meeting of the International Psychogeriatric Association Third
      Congress of the Brazilian Association of Geriatric Neuropsychiatry.

PMID- 29213565
TI  - Selective vulnerability of von Economo neurons in frontotemporal dementia.

PMID- 29213564
TI  - A novel use for an old drug.

PMID- 29213566
TI  - Literacy as a determining factor for brain organization: from Lecours'
      contribution to the present day.
AB  - This review aimed to discuss the influence of literacy and formal education on
      human brain organization, based on evidence drawn from three sources: (1) results
      and limitations of a project coordinated by Andre Roch Lecours on the influence
      of illiteracy on brain organization and of studies on aphasia in illiterate
      populations;(2) data on the impact of schooling on the neuropsychological
      assessment of healthy and brain-damaged individuals, and(3) studies on the effect
      of schooling on dementia. These findings suggest that schooling and literacy
      processes influence cerebral organization of healthy individuals, as well as of
      brain-lesion individuals and those with dementia. Concerning illiteracy, the
      systematic pioneering studies developed by Lecours and the continuity of his
      investigations were essential to alert the scientific and clinical communities to
      take into account the role of educational experience on cognitive processing and
      its brain substrates.

PMID- 29213567
TI  - Contribution of education, occupation and cognitively stimulating activities to
      the formation of cognitive reserve.
AB  - The cognitive reserve (CR) concept posits that there is individual variability in
      processing task demands and coping with neurodegenerative diseases. This
      variability can be attributed to the protective effects derived from continuous
      cognitive stimulation throughout life, including formal education, engagement in
      cognitively stimulating activities and occupation. These can result in protection
      against age-related cognitive decline and reduce the risk of developing
      Alzheimer's disease. The aim of this review is to summarize the main features of
      CR formation and to discuss the challenges in carrying out CR research in
      developing countries.

PMID- 29213569
TI  - Public awareness of dementia: A study in Botucatu, a medium-sized city in the
      State of Sao Paulo, Brazil.
AB  - : Dementia is a progressive and debilitating disease affecting an increasing
      number of people worldwide. Despite its importance, only a few studies have
      examined public awareness of dementia. We present a study of the public awareness
      of dementia in Botucatu, Sao Paulo, Brazil. Methods: A sample of 73 individuals
      answered a questionnaire approved by the Medical Ethics Research Committee
      inquiring about the characteristics of healthy old-aged and demented individuals.
      Results: Those interviewed believed that dementia is characterized by prevalent
      memory impairment (41%) and behavioral changes (32.9%) with onset in the 60's or
      older (42.5%) and upon suspecting dementia, only a few would seek specialized
      medical help. Discussion: Better understanding of public awareness of dementia
      provides the clue to more effective health and social policies in order to
      achieve a higher rate of early diagnosis and thereby possibly decreasing patient,
      family and caregiver distress.

PMID- 29213568
TI  - Alzheimer disease neuropathology: understanding autonomic dysfunction.
AB  - : Alzheimer's disease is a widely studied disorder with research focusing on
      cognitive and functional impairments, behavioral and psychological symptoms, and
      on abnormal motor manifestations. Despite the importance of autonomic
      dysfunctions they have received less attention in systematic studies. The
      underlying neurodegenerative process of AD, mainly affecting cortical areas, has
      been studied for more than one century. However, autonomic-related structures
      have not been studied neuropathologically with the same intensity. The autonomic
      nervous system governs normal visceral functions, and its activity is expressed
      in relation to homeostatic needs of the organism's current physical and mental
      activities. The disease process leads to autonomic dysfunction or dysautonomy
      possibly linked to increased rates of morbidity and mortality. Objective: The aim
      of this review was to analyze the cortical, subcortical, and more caudal
      autonomic-related regions, and the specific neurodegenerative process in
      Alzheimer's disease that affects these structures. Methods: A search for papers
      addressing autonomic related-structures affected by Alzheimer's degeneration, and
      under normal condition was performed through MedLine, PsycInfo and Lilacs, on the
      bibliographical references of papers of interest, together with a manual search
      for classic studies in older journals and books, spanning over a century of
      publications. Results: The main central autonomic-related structures are
      described, including cortical areas, subcortical structures (amygdala, thalamus,
      hypothalamus, brainstem, cerebellum) and spinal cord. They constitute autonomic
      neural networks that underpin vital functions. These same structures, affected by
      specific Alzheimer's disease neurodegeneration, were also described in detail.
      The autonomic-related structures present variable neurodegenerative changes that
      develop progressively according to the degenerative stages described by Braak and
      Braak. Conclusion: The neural networks constituted by the central autonomic
      related structures, when damaged by progressive neurodegeneration, represent the
      neuropathological substrate of autonomic dysfunction. The presence of this
      dysfunction and its possible relationship with higher rates of morbidity, and
      perhaps of mortality, in affected subjects must be kept in mind when managing
      Alzheimer's patients.

PMID- 29213570
TI  - Detecting cognitive impairment in patients with Parkinson's disease with a brief
      cognitive screening tool: the Addenbrooke's Cognitive Examination (ACE).
AB  - : Detecting cognitive impairment in patients with Parkinson's disease is crucial
      for good clinical practice given the new therapeutic possibilities available.
      When full neuropsychological evaluations are not available, screening tools
      capable of detecting cognitive difficulties become crucial. Objective: The goal
      of this study was to investigate whether the Spanish version of the Addenbrooke's
      Cognitive Examination (ACE) is capable of detecting cognitive difficulties in
      patients with Parkinson's disease and discriminating their cognitive profile from
      patients with dementia. Methods: 77 early dementia patients (53 with Alzheimer's
      Disease and 24 with Frontotemporal Dementia), 22 patients with Parkinson's
      disease, and 53 healthy controls were evaluated with the ACE. Results:
      Parkinson's disease patients significantly differed from both healthy controls
      and dementia patients on ACE total score. Conclusions: This study shows that the
      Spanish version of the ACE is capable of detecting patients with cognitive
      impairment in Parkinson's disease and is able to differentiate them from patients
      with dementia based on their general cognitive status.

PMID- 29213571
TI  - Visuospatial cognitive tests for the evaluation of patients with Parkinson's
      disease.
AB  - : Parkinson's disease (PD) is a neurological disorder characterized by motor
      disturbances, neuropsychological symptoms and cognitive changes, including cases
      of dementia. The most frequently described cognitive changes in these patients
      involve executive and visuospatial functions, which are very important for the
      execution of daily life activities. Objective: To compare different tests used to
      examine visuospatial functions in patients with PD. Methods: Thirty-five patients
      (21 women) with PD symptoms (medicated and "on") and mean schooling of 5.5+/-4.2
      years were examined using the following tests: Mini-Mental State Examination
      (MMSE), Dementia Rating Scale (DRS), Scales of Outcomes of Parkinson's Disease
      (SCOPA-COG), Hooper Visual Organization Test (HVOT), Judgment of Line
      Orientation, Form V (JLO), and Clock drawing task - CLOX (1 and 2). Results: The
      mean MMSE score was 24.8+/-3.03and 54.8% of the patients performed correctly in
      the copy of a pentagon drawing, with a medium-level performance in most tests.
      Good correlations were detected between JLO versus SCOPA Assembling patterns
      (0.67), JLO versus HVOT (0.56), JLO versus CLOX2 (0.64), SCOPA Figure Composition
      versus HVOT (0.54), CLOX1 versus CLOX2 (0.43), and DRS Construction versus CLOX2
      (0.42). Discussion: Although correlations were detected, not all were strong,
      probably because the tests employed do not measure solely visuospatial functions,
      but also other skills such as attention, motor ability and executive functions. A
      limitation of the present study was the lack of a control group for the
      establishment of adequate standards for this population.

PMID- 29213572
TI  - Executive cognitive tests for the evaluation of patients with Parkinson's
      disease.
AB  - : Parkinson's disease (PD) is characterized by changes in movement, which are
      later followed by cognitive, behavioral and psychological changes. The objective
      of the present study was to correlate different tests used to examine executive
      functions in PD patients followed at a specialized outpatient clinic. Methods:
      Thirty-five patients with idiopathic PD aged 63.0 years on average and with mean
      schooling of 5.5+/-4.2 years, were examined using the following tests: Mattis
      Dementia Rating Scale (MDRS), Scales for Outcomes of Parkinson's Disease
      Cognition (SCOPA-COG), Wisconsin Card Sorting Test (WCST), Frontal Assessment
      Battery (FAB), Digit Span - Inverse Order (IO) (a subtest of the WAIS III) and
      Verbal Fluency Test (category animals). Results: Significant correlations were
      detected between FAB and MDRS Conceptualization (0.814), MDRS
      Initiation/Perseveration (I/P) and SCOPA-COG Executive Function (0.643), FAB and
      MDRS I/P (0.601), FAB and Verbal Fluency (0.602), MDRS I/P and MDRS
      Conceptualization (0.558), Verbal Fluency and MDRS I/P (0.529), MDRS Attention
      and SCOPA-COG Executive Function (0.495), MDRS Conceptualization and SCOPA-COG
      Executive Function (0.520), FAB and Digit Span (OI) (0.503), Verbal Fluency and
      MDRS Conceptualization (0.501), and WCST perseverative errors and FAB (-0.379),
      WCST perseverative errors and MDRS Conceptualization (0.445), WCST perseverative
      errors and MDRS I/P (-0.407) and WCST categories completed and MDRS
      Conceptualization (0.382). Discussion: The results demonstrated strong
      correlations between most of the tests applied, but no associations were detected
      between the WCST and the other tests, a fact that may be explained by the
      heterogeneity of scores obtained in the tests by the patients evaluated. A
      difficulty of the present study was the lack of a control groups for the
      establishment of adequate standards for this population.

PMID- 29213573
TI  - Association of caregiver demographic variables with neuropsychiatric symptoms in
      Alzheimer's disease patients for distress on the Neuropsychiatric Inventory
      (NPI).
AB  - : Behavioral symptoms are frequently observed in Alzheimer's disease patients and
      are associated to higher distress for patients and caregivers, early
      institutionalization, worst prognosis and increased care. Objectives: The
      objective of the present study was to evaluate the frequency of neuropsychiatric
      symptoms in a sample of Alzheimer's disease patients and to analyze association
      between caregiver demographic characteristics and patient symptoms. Methods:
      Sixty Alzheimer's disease patients (NINCDS-ADRDA) and their caregivers were
      consecutively included in the investigation by the Dementia Outpatient clinic of
      Hospital de Clinicas de Porto Alegre. The Neuropsychiatric Inventory (NPI) was
      applied to evaluate behavioral symptoms and their impact upon caregivers. Age,
      sex, educational attainment, relationship to the patient, and time as caregiver
      were obtained from all caregivers. Results: Apathy was the symptom responsible
      for the highest distress level, followed by agitation and aggression. A
      significant correlation between total severity NPI and distress NPI was observed.
      None of the caregiver demographic data showed association to distress. The most
      frequent symptoms were apathy and aberrant motor behavior. Patients' relatives
      also considered apathy as the most severe symptom, followed by depression and
      agitation. Conclusions: Apathy was the most frequent and severe neuropsychiatric
      symptom. No relationship between caregiver demographic characteristics and
      distress was observed.

PMID- 29213574
TI  - Subclinical naming errors in mild cognitive impairment: A semantic deficit?
AB  - : Mild cognitive impairment (MCI) is the transitional stage between normal aging
      and Alzheimer's disease (AD). Impairments in semantic memory have been
      demonstrated to be a critical factor in early AD. The Boston Naming Test (BNT) is
      a straightforward method of examining semantic or visuo-perceptual processing and
      therefore represents a potential diagnostic tool. The objective of this study was
      to examine naming ability and identify error types in patients with amnestic mild
      cognitive impairment (aMCI). Methods: Twenty aMCI patients, twenty AD patients
      and twenty-one normal controls, matched by age, sex and education level were
      evaluated. As part of a further neuropsychological evaluation, all subjects
      performed the BNT. A comprehensive classification of error types was devised in
      order to compare performance and ascertain semantic or perceptual origin of
      errors. Results: AD patients obtained significantly lower total scores on the BNT
      than aMCI patients and controls. aMCI patients did not obtain significant
      differences in total scores, but showed significantly higher semantic errors
      compared to controls. Conclusion: This study reveals that semantic processing is
      impaired during confrontation naming in aMCI.

PMID- 29213575
TI  - Neuropsychological differences between frontotemporal lobar degeneration and
      Alzheimer's disease.
AB  - : Memory impairment is the main clinical feature in Alzheimer disease (AD),
      whereas in frontotemporal lobar degeneration (FTLD) behavioral and language
      disorders predominate. Objectives: To investigate possible differences between
      the neuropsychological performance in FTLD and AD. Methods: Fifty-six AD patients
      (mean age=72.98+/-7.43; mean schooling=9.62+/-4.68; 35 women and 21 men), 17 FTLD
      patients (mean age=67.64+/-7.93; mean schooling=12.12+/-4.77; 9 women and 8 men),
      and 60 controls (mean age=68.90+/-7.48; mean schooling=10.72+/-4.74; 42 women and
      18 men) were submitted to a Dementia Rating Scale (DRS) and a comprehensive
      neuropsychological evaluation composed of tasks assessing attention,
      visuoperceptual abilities, constructive abilities, executive functions, memory
      and language. Results: DRS total score and subscales were not able to
      differentiate FTLD from AD patients. However, FTLD and AD patients showed
      statistically significant differences in performance in tests of verbal (Logical
      Memory, Rey Auditory Verbal Learning Test) and visual (Visual Reproduction,
      recall of the Rey Complex Figure) episodic memory, verbal immediate memory
      (Logical Memory), attention with interference (Trail Making Test - Part B),
      verbal fluency (semantic and phonemic) and concept formation (WCST). Conclusion:
      Contrary to expectations, only a few tasks executive function tasks (Trail Making
      Test - Part B, F.A.S. and WCST) and two memory tests (verbal and visual episodic
      memory tests) were able to differentiate between FTLD and AD patients.

PMID- 29213576
TI  - Applicability of a cognitive questionnaire in the elderly and proxy.
AB  - : The Informant Questionnaire on Cognitive Decline in the Elderly with the Proxy
      (IQCODE) was developed as a screening tool for cognition alterations. Objectives:
      1) To verify the applicability of IQCODE in the elderly with limited schooling,2)
      To verify the reliability of the responses supplied by the aged and their
      proxies. Methods: Individuals of a Community Group were evaluated using the Mini
      Mental State Examination (MMSE), IQCODE and Geriatric Depression Scale (GDS). The
      IQCODE was applied to informants and proxies. Results: We analyzed 44
      individuals, aged between 58-82 years (M=66.8, SD=5.97) with mean elderly
      schooling level of 3.75, SD=2.82 and 44 proxies aged 44.5 (SD=13.3), with mean
      schooling level of 8.25 (SD=4.3). The mean GDS was 8.22, SD=4.90 and 13
      participants presented a score suggestive of depressive symptoms. The mean
      elderly IQCODE score was 3.26, SD=0.69 and 3.21, SD=0.65, for proxy responses.
      There was no statistical difference between these means. On the MMSE, the mean
      score was 24.20, SD=4.14 and 18 participants presented scores below the cut-off.
      The IQCODE answers by the elderly in this latter group were more congruent with
      MMSE than the answers of proxies. Conclusions: The applicability of the IQCODE in
      a population with little schooling was verified in that the proxy-report was
      similar to the elderly report. We can affirm that the elderly answers were more
      accurate than the proxies, as they were closer to MMSE score. The inclusion of a
      greater number of participants from community-dwelling settings is necessary to
      confirm the results obtained in this study.

PMID- 29213578
TI  - Supplements, homepage, newsletter and mission of the journal.

PMID- 29213577
TI  - Effects of functional physical activity on the maintenance of motor function in
      Alzheimer's disease.
AB  - : It is widely known that older adults, even frail individuals, can improve their
      physical function using appropriately targeted exercise. Nevertheless, older
      adults with Alzheimer's disease (AD) have been excluded from the majority of
      studies on exercise. The functional-task physical activity program is based on
      activities of daily living, and may be suited for elderly people with AD because
      it focuses on the maintenance and stimulation of preserved abilities. In
      addition, session costs are substantially reduced by adopting a group approach.
      Furthermore, the group approach may improve the social interaction of the
      demented patient. Objectives: To determine whether a functional-task physical
      activity program in groups can maintain motor function in elderly with AD.
      Methods: 10 elderly diagnosed with mild or moderate AD were assigned into one of
      two groups: subjects with and without intervention. The intervention consisted of
      a 12-week function-task physical activity program in groups. Measurements:
      activities of daily living (Katz and Lawton & Brody questionnaires), mobility
      (Timed Up and Go Test, Timed Up and Go manual Test and Timed Up and Go Cognitive
      Test), cognition (Mini-Mental State Examination), behavioral disturbances
      (Neuropsychiatric Inventory I-brief) and functional balance (Berg Balance Scale).
      Results: A statistically significant difference between the two groups was found
      regarding the functional balance mean change measured by Berg scale score
      (p=0.046). A significant improvement of 1.60 points (95%CI[0.22;2.98]) was
      observed in the intervention group on this scale, while the non-intervention
      group showed -0.40 points (95%CI[-1.78;0.98], no change). Conclusions: It is
      possible to treat mild and moderate Alzheimer's patients using a group approach.
      The functional task physical activity program was efficient in functional balance
      improvement and also appeared to prevent mobility decline.

PMID- 29213579
TI  - Normal and abnormal aging in bilinguals.
AB  - : Bilinguals use two different language systems to mediate not only social
      communication, but also cognitive processes. Potential differences between
      bilinguals and monolinguals in task-solving strategies and patterns of cognitive
      decline during normal and abnormal aging have been suggested. Main contribution:
      A research review of the area suggests that normal aging is associated with
      increased interference between the two languages and tendency to retreat to a
      single language. General cognitive functioning has been found to be higher in
      demented bilingual patients if communication is carried out in L1 rather than in
      L2. Recent research has reported that bilingualism can have a protective effect
      during aging, attenuating the normal cognitive decline associated with aging, and
      delaying the onset of dementia. Conclusions: Regardless of the significant
      heterogeneity of bilingualism and the diversity of patterns in language use
      during life-span, current research suggests that bilingualism is associated with
      preserved cognitive test performance during aging, and potentially can have some
      protective effect in dementia.

PMID- 29213580
TI  - Event-related potentials and the study of memory retrieval: A critical review.
AB  - Memory retrieval has been extensively investigated by a variety of techniques and
      methodological approaches. The present article reports a critical review on the
      research investigating this subject by means of event-related potentials (ERP).
      The main goal is to elucidate the key contributions of this technique regarding
      episodic memory retrieval, as well as to perform a critical analysis taking into
      account its major advantages and limitations in the framework of current
      cognitive neuroscience. Considerations concerning its theoretical contributions
      and implementation in national universities are also discussed.

PMID- 29213581
TI  - Mild behavioral impairment: A prodromal stage of dementia.
AB  - Mild cognitive impairment (MCI) was defined by Petersen et al. (1999) as
      progressive memory loss, a prodrome of Alzheimer's disease. MCI is a well
      established entity that can be both a diagnosis in medical practice and a valid
      target of Alzheimer's prevention therapy. More recently MCI has expanded to
      include other cognitive domains with other potential causes: amnestic MCI,
      multiple domains MCI, and single domain non-amnestic MCI. Behavioral symptoms in
      MCI are associated with a higher risk of dementia, but their association with
      dementia risk in patients without MCI is unknown. The objective of our paper was
      to address the question of whether aging patients with behavioral symptoms with
      or without cognitive impairment represent a population at risk for dementia. Mild
      Behavioral Impairment (MBI) defines a late life syndrome with prominent
      psychiatric and related behavioral symptoms in the absence of major cognitive
      symptoms. MBI also appears to be a transitional state between normal aging and
      dementia. MBI may carry a higher risk for dementia than MCI. A subgroup of MBI
      patients is likely to exhibit symptoms of a frontotemporal dementia (FTD)
      prodrome. We proposed 4 subtypes of patients at risk for dementia: amnestic MCI
      (which is said to progress preferentially to Alzheimer's disease), multiple
      domain MCI (which may represent normal aging or may progress to vascular
      cognitive impairment or a neurodegenerative disorder), single domain non-amnestic
      MCI, and MBI (which may progress to frontotemporal dementia, Lewy Body dementia
      or Alzheimer's disease). We concluded that MBI is a counterpart of MCI as a
      transitional state between normal aging and dementia. These findings have
      implications for early detection, prevention, and treatment of patients with late
      life dementia.

PMID- 29213582
TI  - Dementia with Parkinson disease: Clinical diagnosis, neuropsychological aspects
      and treatment.
AB  - Dementia with Parkinson's disease represents a controversial issue in the complex
      group of alpha-synucleinopathies. The author acknowledges the concept of a
      "continuum" between Parkinson disease's (PD), Lewy body dementia (LBD), and
      dementia in Parkinson's disease (PDD). However, the practicing neurologist needs
      to identify the phenotypic signs of each dementia. The treatment and prognosis
      are different in spite of the overlaps between them. The main aim of this review
      was to characterize the clinical diagnoses of dementia associated with
      Parkinson's disease (PDD). Secondarily, the review discussed some epidemiological
      and neuropsychological issues. Selection of articles was not systematic and
      reflects the author's opinion, where the main text selected was the
      recommendations from the Movement Disorder Society Task Force for PDD diagnosis.
      The Pub Med, OVID, and Proquest data bases were used for the search.

PMID- 29213583
TI  - Diagnostic disclosure in Alzheimer's Disease: A review.
AB  - Although growing, the literature on research into attitudes of general and
      specialized physicians towards disclosing the diagnosis of dementia and
      Alzheimer's disease (AD), or the current practice on AD disclosure, remains
      limited. Moreover, information is also scarce on what caregivers, or indeed
      patients themselves, wish to know with regard to their diagnosis. The goal of the
      present article was to present a review of the current available literature on
      the topic of truth telling in dementia, especially in AD. The studies discussed
      in this review were mainly conducted in Europe, particularly in the United
      Kingdom, as well as the United States. Disclosure of AD diagnosis is not a common
      practice among physicians. In the clinical context, the discussion on diagnosis
      disclosure can be valuable for improving the care of AD patients and their
      families.

PMID- 29213584
TI  - Behavioral and psychological symptoms in dementia is not a unitary concept: A
      critical review with emphasis on Alzheimer's disease.
AB  - : Behavioral and Psychological Symptoms of Dementia (BPSD) is an important
      feature of dementia. However, this definition comprises a large array of symptoms
      and syndromes. This hampers understanding of the behavior of patients with
      dementia and the devising of strategies to ameliorate these symptoms. Objectives:
      This review aimed to describe the main factors and syndromes that comprise BPSD,
      as well as neuroimaging, psychopharmacological, and genetic data derived from
      studies of these factors. Methods: A search on the Medline, Scielo, and ISI
      databases was performed using the keyword BPSD for articles published within the
      last five years. Selected publications were favored, so this review should not be
      regarded as a systematic study on the subject. Results: The main factors and
      syndromes comprising BPSD were identified, namely psychosis, depression, and
      activity. Different ways of clustering symptoms were considered. The main
      manifestations of psychosis, apathy and depression were focused, relating
      phenomenology to neuroimaging and pharmacological issues. Conclusions: BPSD is a
      heterogeneous array of symptoms which can be better understood as clusters. At
      least three factors can be separated in BSPD, namely psychosis, depression, and
      activity. This division may offer guidance to clinicians regarding treatment
      management and follow up of the chosen therapeutic strategy.

PMID- 29213585
TI  - The corpus callosum in Binswanger's disease: A quantitative fractional anisotropy
      analysis.
AB  - : To study the integrity of the corpus callosum in Binswanger's disease (BD)
      patients using quantitative fractional anisotropy (DTI-FA). Methods: Controls
      (12) and patients with BD (12) were included. MR [GE Signa Horizon-1.5T] scans
      were performed. BD patients presented Fazekas's score=6 and leukoaraiosis
      extension =75%, as assessed on FLAIR sequence. Standard parameters for DTI-FA
      acquisition were used. Functool was employed for post-processing, and ROIs placed
      on the genu and splenium of the corpus callosum on one axial plane at the basal
      ganglia level. Statistics [ANOVA] for genu and splenium comparison were analyzed.
      Results: DTI-FA showed reduction of anisotropy in both regions of the corpus
      callosum, more prominently in anterior (genu) than posterior (splenium) in BD
      patients versus controls. Conclusion: The reduction of anisotropy reflects loss
      of integrity of fibers of the studied regions of the corpus callosum. This
      finding indicates an interruption of the most important inter-hemispheric
      commissure, and component of neural networks that underlies cognitive,
      behavioral, motor and sensory integration. The affected genu and splenium,
      together with damage to other fiber systems that connect the prefrontal and
      parietal-occipital regions, may manifest clinically as dysfunction of high-level
      integrative regions linked to the domains of executive and sensory functions,
      respectively, that can occur in Binswanger's disease.

PMID- 29213586
TI  - Subcortical atrophy in frontotemporal dementia and Alzheimer's disease:
      Significance for the differential diagnosis and correlations with clinical
      manifestations.
AB  - : Cerebral subcortical atrophy occurs in both Alzheimer's disease (AD) and
      frontotemporal dementia (FTD) but its significance for clinical manifestations
      and differential diagnosis between these common types of dementia has not been
      extensively investigated. Objectives: To compare the severity of cerebral
      subcortical atrophy in FTD and AD and to analyze the correlations between
      cerebral subcortical atrophy and demographics and clinical characteristics.
      Methods: Twenty three patients with FTD and 21 with AD formed the sample, which
      comprised 22 men and 22 women, aged 33 to 89, with mean age (+/-SD) of 68.52+/
      12.08 years, with schooling ranging from 1 to 20 years, with a mean (+/-SD) of
      7.35+/-5.54 years, and disease duration with a mean (+/-SD) of 3.66+/-3.44 years.
      The degree of cerebral subcortical atrophy was measured indirectly with a linear
      measurement of subcortical atrophy, the Bifrontal Index (BFI), using magnetic
      resonance imaging. We evaluated cognition, activities of daily living and
      dementia severity with the Mini-Mental State Examination, Functional Activities
      Questionnaire and the Clinical Dementia Rating, respectively. Results: There was
      no significant difference (p>0.05) in BFI between FTD and AD. The severity of
      cognitive deficits (for both FTD and AD groups) and level of daily living
      activities (only for AD group) were correlated with BFI. Conclusions: A linear
      measurement of cerebral subcortical atrophy did not differentiate AD from FTD in
      this sample. Cognitive function (in both FTD and AD groups) and capacity for
      independent living (only in AD group) were inversely correlated with cerebral
      subcortical atrophy.

PMID- 29213587
TI  - Testosterone profile in older men with Alzheimer's disease.
AB  - : Evidence suggests low testosterone levels in Alzheimer's disease. Objectives:
      To compare testosterone levels between older men with and without Alzheimer's
      disease. Methods: Fourteen men with Alzheimer's disease were compared with twenty
      eight men without dementia. Demographic variables and clinical profiles were
      analyzed. Within fifteen days before or after the described evaluation, measures
      of total testosterone and Sex Hormone Binding Globulin (SHBG) were performed.
      Free testosterone level was calculated based on total testosterone and SHBG.
      Quantitative variables were analyzed using Student's t test or Kruskal-Wallis
      test, while qualitative variables were analyzed using chi-square or Fisher test.
      Results: Mean age in the Control and Alzheimer's disease groups were 72.0 (SD+/
      4.8) years and 79.3(SD+/-5.9) years, respectively (p=0.001). Mean schooling
      between these two groups were 8.78 and (+/-5.86) years, respectively (p=0.022).
      There were no statistically significant differences between the two groups for
      testosterone levels, although a trend was observed for the Alzheimer's disease
      group to present lower levels than the control group (p=0.066). There was no
      direct correlation between free testosterone and age, although a trend was
      evident (p=0.068). Conclusions: There was no significant difference in
      testosterone between men with AD and those without dementia.

PMID- 29213588
TI  - Comparison of the Mini Mental State Examination and depressive symptoms between
      high cardiovascular risk and healthy community elderly groups.
AB  - : The aging of the population is a universal phenomenon with direct consequences
      upon the public health system. One of the main repercussions of the growth in
      this sector of the population is the increased prevalence of disorders such as
      dementia and depression which are very frequent among the elderly. The
      relationship between cardiovascular risk factors, dementia and depression have
      been addressed in many recent investigations. Objectives: To evaluate the
      relationship of cognitive performance and depressive symptoms with cardiovascular
      risk in the elderly. Methods: 94 high cardiovascular risk elderly patients and
      160 healthy community elderly were evaluated cross-sectionally. The Mini Mental
      State Examination (MMSE) and the Geriatric Depression Scale (GDS-15) were used as
      the main measures. The cutoff for presence of depression was 6 on the GDS.
      Results: The high cardiovascular risk elderly group showed significantly lower
      scores on the MMSE (p<0.001) and was significantly associated to depression
      (p<0.001), independently of education. The logistic regression analysis for
      depression as the dependent variable, age and group (healthy community or high
      cardiovascular risk elderly) were kept in the final equation. Higher age (Odds
      Ratio=0.92; 95% CI 0.86-0.98) and high cardiovascular risk elderly (OR=2.99; 95%
      CI 1.36-6.59) were associated to depression. Conclusions: The present findings
      corroborate the different cognitive performance of elderly with high
      cardiovascular risk factors and the association of depressive symptoms with this
      group.

PMID- 29213589
TI  - Short IQCODE as a screening tool for MCI and dementia: Preliminary results.
AB  - : Reaching a diagnosis may be difficult in the initial stages of dementia,
      especially in low educated individuals, when informant reports may be useful.
      Objectives: To compare the sensitivity and specificity of the IQCODE against
      cognitive tests applied in clinical practice and to evaluate the possible cut-off
      points in Brazil. Methods: Individuals without dementia (CDR=0; N=5), with Mild
      Cognitive Impairment (MCI) (CDR=0.5; N=15) and demented (CDR>=1; N=29) were
      evaluated using the Short IQCODE, a 16-item questionnaire applied to an
      informant, and on standard cognitive and functional scales. Diagnosis was reached
      by a consensus team with expertise in dementia, according to DSM-IV criteria,
      which was blind to the IQCODE results. Results: IQCODE scores were positively
      correlated to the CDR (r=0.65, p<0.001) and negatively correlated with years of
      schooling (r= -0.33, p=0.021). IQCODE scores were positively correlated with CDR
      controlled by age and education (r=0.61, p<0.001). Linear regression showed that
      age was associated with the IQCODE (p=0.016) whereas education was not associated
      (p=0.078). IQCODE means according to the CDR classification were: CDR 0-3.37; CDR
      0.5-3.75; CDR 1-4.32; CDR 2-4.61; CDR 3-5.00. The area under the ROC curve for
      dementia vs. controls was 0.869 (p<0.001), MCI vs. controls, 0.821 (p<0.001); and
      according to the groups classified by the CDR was: CDR 0.5 vs. CDR 1=0.649
      (p=0.089), CDR 1 vs. CDR 2=0.779 (p=0.009), and CDR 2 vs. CDR 3=0.979 (p=0.023).
      Conclusions: These preliminary findings suggest that the short IQCODE can be used
      for the screening of MCI and dementia in Brazil.

PMID- 29213590
TI  - EXIT25 - Executive interview applied to a cognitively healthy elderly population
      with heterogeneous educational background.
AB  - : Education interferes with the performance in most cognitive tests, including
      executive function assessment. Objective: To investigate the effects of education
      on the performance of healthy elderly on the Brazilian version of the Executive
      Interview (EXIT25). Methods: The EXIT25 was administered to a sample of 83
      healthy elderly. The subjects were also submitted to the Mini-Mental State
      Examination (MMSE), a delayed recall test, clock drawing and category fluency
      (animals/min) tests in order to rule out cognitive impairment. The Geriatric
      Depression Scale (GDS) was employed to exclude clinically-relevant depressive
      symptoms. The total sample was divided into three groups according to educational
      level: G1 (1-4 years), G2 (5-8 years) and G3 (>8 years). Results: The mean values
      for age, educational level, MMSE and EXIT25 scores of all subjects were 72.2,
      7.5, 27.6 and 6.9, respectively. The scores on the EXIT25 for each group were:
      G1=8.3, G2=5.9 and G3=5.8. There was a statistical difference between the
      performance of G1 and the other two groups on the EXIT25. Conclusions: The
      Brazilian version of the EXIT25 proved straightforward to administer. The
      performance of this sample of healthy elderly on the test was significantly
      influenced by educational level.

PMID- 29213591
TI  - Immediate recall of short stories depends on educational level.
AB  - : Memory complaints are frequent in the elderly but the confirmation of memory
      decline is challenging. Tests employing the recall of paragraphs or short stories
      have been proposed for the diagnosis of Alzheimer's disease and amnestic mild
      cognitive impairment. Objectives: To evaluate the influence of educational level
      on immediate recall of short stories. Methods: A sample of 363 individuals (214
      women; median age of 50; median years of schooling of 6; 23 illiterates) without
      evident physical or mental illnesses were evaluated with simple
      neuropsychological tests, including the recall of short stories immediately after
      listening to them read aloud by the examiner. Results: Age showed an inverse
      correlation whereas years of schooling showed a direct correlation with the
      scores on the immediate recall of short stories. As age and years of schooling
      were inversely correlated, logistic regression was employed, which showed that
      only years of schooling had an influence on the performance in the test.
      Conclusions: In populations with heterogeneous educational background, the recall
      of short stories cannot be recommended for the diagnosis of memory impairment. It
      is possible that tests with larger encoding phases are more appropriate for these
      populations. From a broader perspective, information released by radio or TV, as
      well as information disseminated orally in public settings such as hospitals,
      stations or airports may be less well retained by low educated individuals,
      especially when the information is presented only once.

PMID- 29213592
TI  - Clinical conditions and memory complaints in outpatient elderly.
AB  - : Memory complaints are common in elderly, and may be associated with many
      clinical problems. Objective: To identify clinical conditions and possible
      factors related to memory complaints in elderly outpatients presenting at a
      tertiary unit. Methods: Patients with memory complaints and normal cognitive
      screening tests were submitted to clinical and laboratorial testing. Radiological
      evaluation was performed as needed for diagnosis. Results: One hundred and
      seventy-seven subjects were initially evaluated, 12 were excluded because of poor
      and inconsistent memory complaints. Of the remainder, seventeen had criteria for
      dementia diagnosis. Ninety-two (55.4%) had one or more comorbid conditions
      possibly related to their complaints. Major depression was present in 26.0%.
      Sixteen patients (9.6%) had vitamin B12 deficiency, 8 were in use of
      inappropriate medications, and 7 (4.2%) had hypothyroidism. Other conditions
      diagnosed were: generalized anxiety disorder, obstructive sleep apnea syndrome,
      hyperparathyroidism, normal pressure hydrocephalus. Three patients had severe
      hearing loss (in 22 with hearing complaints); one had severe visual impairment
      (in 22 with visual complaints). Conclusions: Comprehensive evaluation was able to
      identify treatable conditions possibly related to memory complaints.

PMID- 29213593
TI  - Influence of brain lesion and educational background on language tests in aphasic
      subjects.
AB  - : In language assessment, several socio-demographic variables must be taken into
      account. Objectives: To characterize the performance of aphasic patients with
      different educational background on language tasks and to compare their
      performance to that of individuals with no language disorders. Methods: Thirty
      aphasic patients and 30 healthy individuals were selected. Patients were divided
      into two groups according to educational level: A (1-4 years) n=15 and B (5-11
      years) n=15. Age ranged from 27 to 78 years. All subjects were submitted to the
      Montreal Toulouse language assessment protocol. The pertinent statistical tests
      were applied. Results: Educational level interfered in the linguistic performance
      of normal subjects but not in that of aphasic subjects, whose performance was
      influenced more by the lesion. Conclusions: The present study can contribute
      toward greater understanding of the influence of lesions and educational
      background on the language performance of aphasic subjects.

PMID- 29213594
TI  - Phonemic verbal fluency and age: A preliminary study.
AB  - : Verbal fluency (VF) has been one of the most frequently used instruments in
      clinics and research, both independently or included in a battery recommended for
      the detection of cognitive alterations. Phonemic-verbal fluency (PVF) is an
      interesting variant for cognitive diagnosis particularly because studies indicate
      that it is less influenced by age. Objectives: 1. To estimate the effects of age
      on PVF tests in their original forms, with the /f/-/a/-/s/ phonemes. 2. To
      estimate the effects of the phoneme /p/ and compare it to the original form in
      item generation. 3. To verify associations between the Token Test (TT), Mini
      Mental State Exam (MMSE) and depressive symptoms on performance with /f/-/a/-/s/
      /p/ phonemes. Methods: Forty-eight healthy individuals with ages ranging from 30
      to 80 years were evaluated with the MMSE, TT and PVF tests. Results: Age was
      correlated with the MMSE, TT and depressive symptoms. There was no association
      between age and performance on the fluency test, independent of the phoneme used.
      Among the socio-demographic factors studied, age had a significant impact on
      performance. There was no phoneme effect in item-generation, when comparing the
      traditional form of VF (/f/-/a/-/s/) and the /p/ phoneme. Conclusions: The
      traditional form of FAS is interchangeable with the modified presentation,
      therefore both forms may be used in clinical or research settings. PVF is a
      valuable approach for detecting cognitive alterations in the aged, given its
      stability throughout the ageing process.

PMID- 29213595
TI  - Preliminary data on a mnemonic instrument with proverbs for tracking Alzheimer's
      disease.
AB  - : In the differential diagnosis between Alzheimer's disease (AD) and normal
      aging, tests evaluating memory and executive functions are frequently used. The
      addition of abstraction tests may enhance the effectiveness of screening tests
      for AD. Objectives: The aim of this study was to compare initial data of a new
      instrument - The Screening Test for Alzheimer's Disease with Proverbs (STADP) -
      against other screening tests used in AD diagnosis. Methods: Sixty elderly
      individuals (46 controls and 14 AD subjects with CDR=1), aged =60 years, with at
      least one year of schooling, were evaluated using the STADP at outpatient clinic.
      The STADP assesses short-term memory, episodic memory, executive functions and
      language, in addition to proverb recognition. The performance of the participants
      on the Mini-Mental State Examination (MMSE), semantic Verbal Fluency (VF) and
      Clock Drawing Test (CDT) were evaluated and the habit of reading, writing and
      sociodemographic data were also taken into account. Results: There were
      significant correlations between STADP and the performance on the MMSE (r=0.64),
      CDT (r=0.50) and VF (r=0.56). Age influenced all sub-items of the STADP,
      specifically episodic memory (r= -0.54), whereas schooling mainly influenced
      executive functions and language (r=0.46). The total score, stages A and C and
      the "proverb recognition" of STADP (p<0.001), as well as the MMSE (p<0.001), CDT
      (p=0.016), VF (p<0.001) were significantly different in AD versus control groups.
      Conclusions: The findings point to the potential use of the STADP in AD,
      warranting the conducting of further studies.

PMID- 29213596
TI  - Processing of metaphors in transcortical motor aphasia.
AB  - : Great emphasis has been placed on the right hemisphere, due to its possible
      selective contribution, in the processing of metaphorical statements. Objectives:
      To describe the processing of metaphors in the case of a patient with
      transcortical motor aphasia, using specific tests for patients with encephalic
      injuries of the right hemisphere, and to contribute to the discussion on the
      inter-hemispheric relationships associated with this function. Methods: A 54 year
      old man with transcortical motor aphasia was evaluated three years after a left
      hemisphere stroke. The tasks of comprehension of metaphors were based on the
      subtest Metaphor Comprehension Task of the Montreal Evaluation of Communications
      Scale (MEC). Two metaphor comprehension tests were applied, in 45-minute sessions
      with a 48 hour interval between each. Test 1 involved comprehension of the
      metaphors according to the options offered, and Test 2 the comprehension of
      metaphors measured by response time and visual field. Results: Although the right
      hemisphere was not affected by the stroke in this case, difficulties were
      observed in the processing of metaphors. Conclusions: This study suggests that
      the left hemisphere participates in the processing of figurative meanings. The
      adaptability of the brain can also re-accommodate the uninjured areas of the
      brain, causing the dynamic of the brain to be modified. As a result, deducing
      cerebral functions based on clinical data can be problematic. The value of this
      study is that it can contribute to clinical aspects of language rehabilitation.

PMID- 29213597
TI  - Sustained attention assessment of narcoleptic patients: two case reports.
AB  - Narcolepsy is a sleep disorder characterized by uncontrollable REM sleep attacks
      which alter the patients wake state and can lead to difficulties in attention
      aspects, such as maintaining attention when performing activities or tasks. This
      study aimed to evaluate sustained attention performance of two narcoleptic
      patients on the d2 Test, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality
      Index (PSQI) and Hamilton Rating Scale for Depression (HAM-D). Results showed
      that the maintenance of attention was associated with a slowing of the target
      symbols processing function in visual scanning with accuracy in task performance.
      A high degree of excessive sleepiness was observed, along with mild and moderate
      degrees of depressive signs and symptoms. One subject also presented with a
      nocturnal sleep disorder which could represent an important factor affecting
      attentional and affective capacity.

PMID- 29213598
TI  - Developmental prosopagnosia and adaptative compensatory strategies: Case study.
AB  - : Prosopagnosia is a type of visual agnosia with inability to identify faces,
      usually secondary to brain lesion in associative cortex areas, but there is also
      a congenital form known as developmental prosopagnosia. Objectives: To describe a
      case of developmental prosopagnosia that illustrates the specificity of the
      pathways for perception of faces in the visual system. Also, we will describe
      possible mechanisms of recognition used by this patient. Methods: R.S., a 50 year
      old woman, was referred for neuropsychological assessment due to difficulties in
      perception of familiar faces since childhood, unexplained by any loss of visual
      acuity. Results: The exam showed good performance for comprehension, reasoning,
      concept formation, constructional abilities, criticism, judgment, mental control,
      memory and visual perception for other kinds of stimuli. No difficulties were
      seen regarding identification of ethnicity, age and types of animals. The patient
      was able to match celebrities' faces in different positions, but could not
      identify the matching pictures for unknown people. Conclusions: These findings
      indicate the patient had developed strategies, throughout life, to recognize
      familiar faces (relatives, celebrities) from memorized fragments, but still had
      difficulties in identifying non-familiar faces holistically.

PMID- 29213599
TI  - Postencephalitic amnesia with long term-working memory impairment: A case report.
AB  - Herpes simplex virus encephalitis (HSVE) is an inflammation of the brain
      parenchyma caused by virus, leading to focal necrosis in medial temporal lobes,
      hippocampal complex and basal forebrain. Cognitively, HSVE is associated to many
      dysfunctions which vary according to the extent of the lesion. Episodic memory
      impairment is the most common sequelae following HSVE episodes, although others
      can occur. The aim of this case report was to describe the cognitive profile of a
      42 year-old man who had extensive bilateral damage to the medial temporal lobe,
      insular bilateral and orbitofrontal cortices due to HSVE. Severe anterograde and
      retrograde amnesia, naming deficits, perseverative behaviors and confabulations
      were observed on neuropsychological assessment. We discussed the concept of long
      term-working memory based on this evaluation. These cognitive impairments
      corroborated HSVE previous findings in the literature.

PMID- 29213600
TI  - Pain and apathy.
AB  - In this case report we discuss the lack of emotional reactivity and evasive motor
      motivation to nociceptive stimuli presented by a patient with frontotemporal
      degenerative disease and apathy as a predominant behavioral symptom.

PMID- 29213601
TI  - Dementia in the developing world.

PMID- 29213602
TI  - Argyrophilic grain disease: an update about a frequent cause of dementia.
AB  - Argyrophilic grain disease (AGD) is a sporadic, very late-onset tauopathy,
      accounting for approximately 4-13% of neurodegenerative dementias. AGD may
      manifest with a range of symptoms such as cognitive decline and behavioral
      abnormalities. To date, no study has been able to demonstrate a distinct clinical
      syndrome associated with AGD. The diagnosis is exclusively based on postmortem
      findings, the significance of which remains controversial because up to 30% of
      AGD cases are diagnosed in subjects without any cognitive impairment, while AGD
      findings often overlap with those of other neurodegenerative processes.
      Nevertheless, the presence of AGD is likely to have a significant effect on
      cognitive decline. The neuropathological hallmarks of AGD are argyrophilic
      grains, pre-neurofibrillary tangles in neurons and coiled bodies in
      oligodendrocytes found mainly in the entorhinal cortex and hippocampus. This
      review aims to provide an up-to-date overview of AGD, emphasizing pathological
      aspects. Additionally, the findings of a Brazilian case series are described.

PMID- 29213603
TI  - Normal pressure hydrocephalus: Diagnostic and predictive evaluationon.
AB  - In typical cases, normal pressure hydrocephalus (NPH) manifests itself with the
      triad of gait disturbance, which begins first, followed by mental deterioration
      and urinary incontinence associated with ventriculomegaly (on CT or MRI) and
      normal cerebrospinal fluid (CSF) pressure. These cases present minor diagnostic
      difficulties and are the most likely to improve after shunting. Problems arise
      when NPH shows atypical or incomplete clinical manifestations (25-50% of cases)
      or is mimicked by other diseases. In this scenario, other complementary tests
      have to be used, preferentially those that can best predict surgical outcome.
      Radionuclide cisternography, intracranial pressure monitoring (ICP) and lumbar
      infusion tests can show CSF dynamics malfunction, but none are able to confirm
      whether the patient will benefit from surgery. The CSF tap test (CSF-TT) is the
      only procedure that can temporarily simulate the effect of definitive shunt.
      Since the one tap CSF-TT has low sensitivity, it cannot be used to exclude
      patients from surgery. In such cases, we have to resort to a repeated CSF-TT
      (RTT) or continuous lumbar external drainage (LED). The most reliable prediction
      would be achieved if RTT or LED proved positive, in addition to the occurrence of
      B-waves during more than 50% of ICP recording time. This review was based on a
      PubMed literature search from 1966 to date. It focuses on clinical presentation,
      neuroimaging, complementary prognostic tests, and differential diagnosis of NPH,
      particularly on the problem of selecting appropriate candidates for shunt.

PMID- 29213604
TI  - Cognitive impairment in Wilson's disease.
AB  - Wilson's disease (WD) or hepatolenticular degeneration is a rare, genetic and
      systemic disease, caused by a deficit in the metabolism of copper, leading to its
      accumulation in different organs, mainly the liver, followed by the central
      nervous system, especially the basal ganglia. When symptoms begin between the
      second and third decades of life, approximately 50% of the patients show
      neurological symptoms. Although dystonia and dysarthria are the most common
      neurological signs, cognitive changes have been reported since the first cases
      were described in 1912. Memory change is one of the most common impairments, but
      other cognitive changes have been reported, including dementia in untreated
      cases. In this article we review the cognitive changes in WD patients and the
      occurrence of dementia.

PMID- 29213605
TI  - Stroke and brain atrophy in chronic Chagas disease patients: A new theory
      proposition.
AB  - Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in
      developing countries. Brain damage in CD has been attributed exclusively to the
      effects of structural heart disease on the brain, including cardioembolism and
      low cardiac output symptoms. However, CD patients also develop stroke and brain
      atrophy independently of cardiac disease severity. Chronic inflammation directed
      against T. cruzi may act as a trigger for endothelial damage, platelet
      activation, acceleration of atherosclerosis and apoptosis, all of which lead to
      stroke and brain atrophy. In the present article, evidence supporting this new
      theory is presented, along with considerations towards mechanistically-based
      targeted treatment.

PMID- 29213606
TI  - Cognitive dysfunction in chronic Chagas disease cardiomyopathy.
AB  - : Chagas disease (CD) remains a major cause of stroke in developing countries,
      but cognitive repercussion of CD has not been well studied. Objective: To compare
      the frequency and pattern of cognitive dysfunction in patients with CD
      cardiomyopathy (CDC) and other cardiomyopathies (OC). Methods: We studied 37
      patients with CDC and 42 patients with OC with similar age, educational level and
      cardiac systolic function. Cognitive tests were applied to both groups by a
      single examiner blinded to CD status. Logistic regression multivariable models
      were constructed to ascertain predictors of cognitive dysfunction for each test.
      Results: Cognitive dysfunction was detected in 9 (24%) CDC patients and 6 (14%)
      OC patients by Mini Mental State Exam (MMSE) corrected for educational level.
      Independent predictors of abnormal MMSE (p<0.05) included stroke history
      (OR=5.51; 95% CI=1.27-24.01) and digoxin use (OR=0.23, 95% CI=0.06-0.89), while
      CD showed a trend toward statistical significance (OR=4.63; 95% CI=0.87-24.73,
      p=0.07). Delayed recall of Rey's Complex Figure Test was significantly worse in
      CD patients, where this remained a significant predictor in the multivariable
      analysis (OR=4.67; 95% CI=1.23-17.68). Conclusions: Cognitive dysfunction is
      frequent in Chagas disease and should be considered as an outcome measure in
      Chagas disease studies.

PMID- 29213607
TI  - Lack of executive functions deficits among adult ad hd individuals from a
      Brazilian clinical sample.
AB  - : Executive function deficits have been previously documented in individuals with
      Attention Deficit Hyperactivity Disorder (ADHD). Objective: The current study
      aimed to compare measures of executive functions among a clinical sample of
      adults with ADHD and normal control subjects, matched for age, gender and
      education. Methods: Twenty-three self-referred adults diagnosed with ADHD
      according to DSM-IV criteria, and twenty-five control subjects were assessed
      using a neuropsychological battery which included the Wisconsin Card Sorting
      Test, Tower of Hanoi, Digit Span, Trail Making Test (A and B), Stroop Test and
      Raven's Progressive Matrices. Results: The ADHD group did not differ
      significantly from the control subjects on any of the measures assessed.
      Conclusion: Measures of executive functions using this test battery were unable
      to discriminate between adults with ADHD and control subjects in this clinical
      sample.

PMID- 29213608
TI  - Do attention deficit/hyperactivity disorder symptoms exist among Brazilian
      indigenous children?
AB  - : The validity of the clinical constructs of attention deficit hyperactivity
      disorder (ADHD) has been generalized for all human populations of different
      cultures worldwide. Yet important population groups have yet to be adequately
      studied so as to definitively confirm this generalization. Objective: To
      investigate the presence of symptoms of ADHD in children living within an
      indigenous community. Methods: We performed interviews in a bid to screen for
      symptoms of ADHD among settlement-dwelling indigenous children of the Karaja
      ethnic group in the Brazilian Amazonian Region. Results: Three narratives are
      presented highlighting the classical symptomatological triad of ADHD:
      inattentiveness, hyperactivity and impulsiveness. Conclusions: Some of ADHD's
      major characteristics, described in the most common disease classification
      worldwide, are clearly described by children of this population. We concluded
      that ADHD symptoms are present in this population which diverges greatly in
      cultural issues compared to the Western world.

PMID- 29213609
TI  - Comparison of performance in neuropsychological tests in amnestic Mild Cognitive
      Impairment and Alzheimer's disease patients.
AB  - : Mild Cognitive Impairment (MCI) can be an intermediate state between normality
      and dementia in some patients. An early diagnosis, through neuropsychological
      assessment, could identify individuals at risk of developing dementia. Objective:
      To verify differences in performance on neuropsychological tests among controls,
      amnestic MCI (aMCI) and Alzheimer's disease (AD) patients. Methods: Sixty-eight
      AD patients (mean age 73.77+/-7.24; mean schooling 9.04+/-4.83; 40 women and 28
      men), 34 aMCI patients (mean age 74.44+/-7.05; mean schooling 12.35+/-4.01; 20
      women) and 60 controls (mean age 68.90+/-7.48; mean schooling 10.72+/-4.74; 42
      women) were submitted to a neuropsychological assessment composed of tasks
      assessing executive functions, language, constructive abilities, reasoning and
      memory. Results: There were statistically significant differences in performance
      across all tests among control, aMCI and AD groups, and also between only
      controls and AD patients. On comparing control and aMCI groups, we found
      statistically significant differences in memory tasks, except for immediate
      recall of Visual Reproduction. There were also statistically significant
      differences between aMCI and AD groups on tasks of constructive and
      visuoperceptual abilities, attention, language and memory, except for delayed
      recall of Visual Reproduction. Conclusions: Neuropsychological assessment was
      able to discriminate aMCI from AD patients in almost all tests except for delayed
      recall of Visual Reproduction, visual organization (Hooper) and executive
      functions (WCST); and discriminate controls from AD patients in all tests, and
      controls from aMCI patients in all memory tests except for immediate recall of
      Visual Reproduction.

PMID- 29213610
TI  - Age and educational level effects on the performance of normal elderly on
      category verbal fluency tasks.
AB  - : Cognitive decline, particularly executive dysfunction, is observed in normal
      aging. In Brazil, the elderly population presents broad educational diversity.
      Category verbal fluency tests are frequently used to detect cognitive impairment,
      assessing executive function, language and semantic memory. Objective: To
      investigate the effects of age and education on category animal fluency task
      (CAF) in healthy elderly. Methods: We evaluated 319 healthy elderly from
      outpatient care units of two university reference centers of Rio de Janeiro and
      Sao Paulo. The sample was divided into two age, and five schooling subgroups. To
      be included participants had to demonstrate preservation of global cognitive
      functioning, independence for activities of daily living and not fulfill
      diagnostic criteria for dementia. All participants were submitted to neurological
      and neuropsychological evaluations. Results: There was a correlation between age
      and CAF performance (r= -0.26, p<0.01), which was not confirmed when years of
      education were included as a covariant in univariate ANCOVA. Significant
      differences were found in CAF performance among the different educational level
      groups on correlation analysis (r=0.42, p<0.01) and ANCOVA analysis (F=18.8,
      p<0.05). Illiteracy was associated with worst CAF performance, while university
      level was associated with best performance. Conclusion: The best CAF performance
      was found in the first years of schooling (literacy learning process) compared to
      illiteracy, and when finishing high school and starting university courses
      compared to all other educational levels. These stages are associated with
      significant gains in semantic memory and executive function which are critical
      for verbal fluency performance.

PMID- 29213611
TI  - Normative data for healthy elderly on the phonemic verbal fluency task - FAS.
AB  - : Phonemic verbal fluency tests assess the production of words beginning with
      specific letters. Of these letters, the most frequently used are F, A and S. It
      is a sensitive test for assessing frontal lobe functions. Objective: To provide
      normative data for the elderly Brazilian population on the FAS test and to
      investigate the effects of age and schooling on test performance. Methods: The
      individuals were divided into three age groups (60-69, 70-79 and =80 years), and
      into four groups according to education (1-3, 4-7, 8-11 and 12 years). All
      subjects were assessed by the Mini Mental State Examination and the FAS. Data
      were analyzed with Student's t test, ANOVA, simple linear regression and
      Spearman's correlation. Results: We evaluated 345 cognitively healthy volunteers,
      66.66% being female, aged 60 to 93 years, with an educational level ranging from
      one to 24 years. The average (number of items) +/-SD for the whole sample was
      28.28+/-11.53. No significant effect of gender was observed (p=0.5). Performance
      on the MMSE and education exerted a direct influence on FAS scores (p<0.001),
      with education being the most significant factor. A positive correlation was
      found between FAS and the MMSE (r=0.404; p<0.001). Conclusion: The performance of
      Brazilian elderly on the phonemic verbal fluency tests-FAS is significantly
      influenced by education, where individuals with higher educational level present
      better performance than those with fewer years of schooling. Age and gender did
      not prove significant with the FAS.

PMID- 29213612
TI  - Charles Bonnet Syndrome: Case series.
AB  - : Since its first description in 1760, Charles Bonnet syndrome (CBS) has been
      reported in many studies. The main characteristics are visual hallucinations,
      preserved awareness of unreal visions, and absence of psychotic symptoms. CBS can
      occur with lesions located anywhere along the central visual pathway, from the
      eye to the calcarine fissure. Objective: To describe patients with CBS and carry
      out a review of the literature. Methods: Six patients with visual hallucinations
      were evaluated in an outpatient memory clinic between 2001 and 2008, and their
      clinical characteristics recorded. Results: Four patients were female, and the
      mean age was 74.5+/-16.9 years. Three patients had visual loss secondary to eye
      disease and three due to cerebral lesions. The visions consisted of animals,
      persons, moving objects, bizarre creatures or colored forms, and were considered
      disturbing by five patients. Five patients received treatment, and only three
      reported partial benefit from the therapy. Complete recovery was not seen in any
      of the subjects. Conclusions: CBS is relatively rare and its recognition is
      important to avoid misdiagnoses with psychiatric or dementing illnesses.

PMID- 29213614
TI  - LILACS, mission and abstracts.

PMID- 29213613
TI  - Dementia post-radiotherapy: improvement with acetylcholinesterase inhibitor. A
      case report.
AB  - Cognitive decline associated with radiotherapy is a progressive complication that
      affects many patients submitted to this form of treatment. The lack of an
      effective treatment drives research for new treatment options to improve the
      quality of life of patients with this disorder. We report the case of a 64 year
      old man who developed a severe dementia of the frontal subcortical type, which
      was associated with subcortical frontal lesions and appeared as a late
      complication of radiotherapy used to treat a pituitary tumor. After many
      pharmacological attempts to improve his cognitive and behavioral problems, the
      patient showed a significant improvement in the cognitive, functional and
      behavioral impairments after treatment with an acetylcholinesterase inhibitor.
      This report discusses hypotheses for the positive effect of this treatment.

PMID- 29213615
TI  - The Clock Drawing Test: A review of its accuracy in screening for dementia.
AB  - : The Clock Drawing Test (CDT) is a simple neuropsychometric instrument that can
      be easily applied to assess several cognitive functions. Over the past 20 years,
      the CDT has aroused considerable interest in its role for the early screening of
      cognitive impairment, especially in dementia. Although the CDT is considered an
      accurate test for dementia screening, recent studies including comparisons with
      structured batteries such as the CAMCOG have shown mixed results. Objectives: To
      investigate the importance of the CDT compared to other commonly used tests, in
      the diagnosis of dementia in the elderly; (2) to evaluate the reliability and
      correlation between available CDT scoring scales from recent studies. Methods: A
      systematic search in the literature was conducted in September 2008 for studies
      comparing CDT scoring systems and comparing the CDT with neuropsychiatric
      batteries. Results: Twelve studies were selected for analyses. Seven of these
      studies compared CDT scoring scales while five compared the CDT against the
      CAMCOG and the MMSE. Eight studies found good correlation and reliability between
      the scales and the other tests. Conclusion: Despite the mixed results in these
      studies, the CDT appears to be a good screening test for dementia.

PMID- 29213616
TI  - The performance of the Mini-Cog in a sample of low educational level elderly.
AB  - Objectives: To study the criterion validity of the Mini-Cog in low educational
      level elderly.Design: Cross-sectional and validation design.Setting: Policlinica
      Piquet Carneiro, an outpatient unit of Rio de Janeiro State University Hospital,
      in Brazil.Participants: A convenient sample consisting of 306 individuals, 65 yrs
      or older, selected from April 8th to July 15th, 2002. Methods: All participants
      underwent comprehensive geriatric evaluations which included the Mini-Mental
      State Examination (MMSE) and the cognitive part of the Cambridge Examination for
      Mental Disorders of the Elderly - Revised (CAMCOG-R). They were classified as
      demented or non-demented (DSM-IV). A post-hoc analysis was performed on the data
      from the 3 word recall test of the MMSE, and the Clock Drawing Test from the
      CAMCOG-R, and respective scores were added and interpreted in accordance with the
      Mini-Cog protocol. Results: 293 individuals completed all the study steps; 211
      had 4 or less years of schooling and were included in the data analysis. 32% had
      dementia. Mini-Cog sensitivity and specificity was consistently low independently
      of the different cut-off points considered. The best performance was found at the
      cut-off point of 2/3 which yielded sensitivity and specificity of 60% and 65%,
      respectively. Conclusion: The Mini-Cog is not a good cognitive screening tool for
      individuals with less than five years of formal education.

PMID- 29213617
TI  - Evaluation of Mini-Mental State Examination scores according to different age and
      education strata, and sex, in a large Brazilian healthy sample.
AB  - : Until better measures have been accepted for wider use, the Mini-Mental State
      Examination (MMSE) will continue to be utilized. In this context, knowledge on
      characteristics and determinants of its distribution for the Brazilian population
      are particularly valuable. The present study aimed to evaluate, based on
      multivariate analysis, the independent effect of age, educational level and sex,
      and their interactions, on MMSE scores in a healthy sample. Methods: Demographic
      data and scores on the MMSE of 1,553 healthy individuals were analyzed. The
      sample was grouped according to age and education. Results: The sample was
      composed of 963 females (62%), mean age +/-SD was 49.6+/-20.7yrs (range 20 to 92
      yrs). The mean years of education +/-SD was 8.9+/-5.5yrs (range 0 to 28 yrs). The
      mean score +/-SD on the MMSE was 27.3+/-2.7(range 15 to 30). A significant effect
      of the interaction between education and sex (p=0.011), and also between
      education and age was observed (p=0.003). An independent effect of education
      (p<0.001) and age (p<0.001) was found. Participants from the higher educated
      group presented higher MMSE scores than the other groups. Younger adults
      presented higher MMSE scores than the other age groups. Conclusions: We observed
      an effect of education and age on MMSE scores. Younger individuals and higher
      educated participants presented higher scores.

PMID- 29213618
TI  - The relationship between memory complaints and age in normal aging.
AB  - : Normal aging can be characterized by a gradual decline in some cognitive
      functions, such as memory. Memory complaints are common among older adults, and
      may indicate depression, anxiety, or cognitive decline. Objectives: To
      investigate the association between memory complaints and age in cognitively
      unimpaired older adults, and the relationship between memory complaints and
      memory performance. Methods: Cognitive screening tests as well as memory
      complaint questionnaires validated for the Brazilian population were used: the
      Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Memory
      Complaint Questionnaire (MAC-Q), Memory test of 18 pictures, Forward and Backward
      Digit Span (WAIS-III). Fifty seven regular members of the SESC social club
      participated (50 women), having a mean age of 71.4 years, and 4 to 8 years of
      education - 34 from 4 to 7 years and 23 with 8 years of education. Results:
      Results revealed no significant association between cognitive complaints and age
      or cognitive performance. Older participants in this sample did not show worse
      performance or a higher level of complaints. There was no significant association
      between age and GDS scores. Conclusions: The studied sample constitutes a
      particular group of older adults whose participation in activities may be
      protecting them from cognitive decline, thus highlighting the impact of lifestyle
      on cognitive performance during the aging process.

PMID- 29213619
TI  - Study on the Behavioural Assessment of the Dysexecutive Syndrome (BADS)
      performance in healthy individuals, Mild Cognitive Impairment and Alzheimer's
      disease: A preliminary study.
AB  - : Executive deficits as well as deficits in episodic memory characterize the
      initial phases of Alzheimer Disease (AD) and are clinically correlated to
      neuropsychiatric symptoms and functional loss. Patients with Mild Cognitive
      Impairment present more problems as to inhibitory response control, switching and
      cognitive flexibility. Objective: To compare performance on the BADS with
      performance on other executive functional tests among patients with mild
      Alzheimer's disease, Amnestic Mild Cognitive Impairment (aMCI) to performance of
      control individuals and to examine discriminative capacity of BADS among these
      groups. Methods: The BADS was performed by 35 healthy controls, 13 patients with
      aMCI, and 16 mild probable AD patients. Besides performing the BADS, subjects
      underwent neuropsychological evaluation which comprised: the Dementia Rating
      Scale (DRS), verbal fluency by phonemic categories (F.A.S) and Concentrated
      Attention Test (CA). Results: There were no differences among groups by
      educational level, but performance differed for age (p<0.01). No difference
      between healthy controls and aMCI patients was found on total scores or subitems
      of the BADS. A significant difference was observed between aMCI and AD patients
      (p<0.05) and between controls and AD patients (p<0.05) on total and standard
      scores. Conclusions: Performance on the BADS differed between healthy individuals
      and mild AD patients. The BADS proved to be a sensitive method for discriminating
      AD from aMCI.

PMID- 29213620
TI  - Nonverbal dichotic test in patients with epilepsy.
AB  - : Auditory processing during childhood may be altered if there is any
      predisposing factor during the course of development. Neurological disorders are
      among the risk factors for auditory processing disorders. Some studies have shown
      verbal auditory processing disorder in children with epilepsy. Objective: To
      verify the performance of children with epilepsy on a nonverbal dichotic test.
      Methods: Thirty-eight subjects, 23 female and 15 male, ranging from 7 to 16 years
      of age with neurological diagnosis of idiopathic epilepsy, without clinical or
      imaging evidence of cerebral lesion were evaluated. Patients were divided into
      two groups: 23 patients diagnosed with partial seizures and 15 patients with
      generalized seizures. Illiterate children, children with hearing thresholds
      exceeding the normal range and with brain lesions confirmed either clinically or
      by imaging tests were excluded from the study group. Results: Analysis of the
      performance of epileptic patients with partial and generalized seizures on the
      Nonverbal Dichotic Test revealed that the majority of patients with epilepsy
      showed impairments in the test, with no significant differences related to
      seizure type, generalized or partial. Although patients with partial and
      generalized seizures performed similarly, all the epileptic patients showed
      different performance to a normal population. Conclusions: This study revealed a
      high prevalence of impairments among epileptic patients in relation to nonverbal
      processing in a dichotic paradigm.

PMID- 29213621
TI  - N-Back auditory test performancein normal individuals.
AB  - : The working memory construct refers to the capacity to maintain information for
      a limited time. Objectives: To devise stimuli and adapt the 5-back test and to
      verify the effect of age in normal Brazilian individuals. Methods: 31 healthy
      adults (15 young adults and 16 older adults) were evaluated by batteries of
      auditory stimuli to verify the inter-group differences (age effect) in working
      memory span, total correct answers and intrusions, and the intra-group effect of
      type of stimulus. Results: There was no intra-group stimulus effect. Individuals
      from both groups processed di and tri-syllables similarly. No difference between
      groups (no age effect) was observed for any N-Back parameters: total score, span,
      number of intrusions, in either di or tri-syllable presentation. Conclusion: the
      processing capacity of 5 elements in phonological working memory was not affected
      by age.

PMID- 29213622
TI  - Comprehension and storage of sequentially presented radio news items by healthy
      elderly.
AB  - : In the normal aging processes, complaints of memory loss and auditory
      comprehension are not uncommon, principally in complex and cognitively demanding
      situations. Objective: The objective of this study was to investigate skills of
      discourse comprehension and retention in a natural situation, by healthy aged in
      relation to variables such as age, schooling and cognitive screening measurement.
      Methods: Thirty healthy elderly participated in the study (mean age=73.56 yrs;
      SD=6.26 and mean schooling=8.6 yrs; SD=4.41). Twelve news items were recorded and
      presented in three sequences of four news-groups. Participants were instructed to
      listen to the four news items, and upon completion were questioned about one of
      them. Results: We found no age or schooling effect on the performance of the
      subjects. The participants achieved almost full scores on all answers (ceiling
      effect). Discussion: The heterogeneity of elderly and cognitive compensation in
      natural situations could explain these results of elderly behavior.

PMID- 29213623
TI  - Cognitive training in older adults with Mild Cognitive Impairment: Impact on
      cognitive and functional performance.
AB  - : Aging is associated with cognitive decline, yet this does not prevent older
      adults from finding ways to compensate for age-related deficits. Earlier studies
      have shown that cognitively unimpaired older adults can benefit from training
      programs. The efficacy of cognitive interventions among older adults without
      dementia but with cognitive decline (mild cognitive impairment, MCI) has not yet
      been widely tested. Objectives: To evaluate the impact of 8-session cognitive
      training on the cognitive and functional performance of older adults with MCI.
      Methods: 16 older adults diagnosed with MCI received cognitive training (18
      participated as controls). All participants were assessed pre and post
      intervention using the Short Cognitive Test (SKT), Direct Assessment of
      Functional Scale Revised (DAFS-R), Geriatric Depression Scale (GDS), and Clock
      Drawing Test (CDT). Results: A significant improvement was observed in the study
      group between pre and post-test in attention (SKT), time orientation, shopping
      skills and dealing with finances (DAFS-R) along with reduced depressive symptoms
      (GDS). Conclusion: These results indicate the importance of non-pharmacological
      interventions for older adults with MCI to help compensate for cognitive decline.

PMID- 29213625
TI  - New approaches to neglected phenomena.

PMID- 29213624
TI  - Dementia caregiver burgen in a brasilian sample: Association to neuropsychiatric
      symptoms.
AB  - : Taking care of elderly demented individuals, especially when they present
      behavioral changes, can be very exhaustive for both family and caregivers.
      Generally, this leads to changes in the family lifestyle, and the caregiver must
      deal with a range of problems. Information on this topic in Latin America,
      including Brazil, remains scarce. Objective: To investigate the relationship
      between the presence of neuropsychiatric symptoms and the level of caregiver
      burden in a group of Brazilian elderly with dementia. Methods: The Brazilian
      versions of the Zarit Caregiver Burden Interview (ZBI) and of the
      Neuropsychiatric Inventory (NPI) were administered to a total of 83 family
      caregivers of patients with dementia followed at a university-affiliated
      outpatient clinic. Pearson's correlations were calculated to measure the level of
      association between the scores on both instruments. Results: Among the
      caregivers, 83.1% were women, and had a mean age of 55.6+/-12.8 years. The ZBI
      scores ranged from 3 to 79 (mean=31.4). Patients' NPI scores ranged from 0 to 102
      (mean=26.9), consistent with a significant degree of behavioral manifestations in
      most patients. A significant positive correlation was found between ZBI and NPI
      scores (r=0.402; p=0.000). Conclusion: The presence and severity of behavioral
      manifestations assessed by the NPI were associated with a high level of caregiver
      burden in this sample of Brazilian elderly with dementia.

PMID- 29213626
TI  - Cognitive dysfunction in spinocerebellar ataxias.
AB  - : Spinocerebellar ataxias (SCAs) comprise a heterogeneous group of complex
      neurodegenerative diseases, characterized by the presence of progressive
      cerebellar ataxia, associated or otherwise with ophthalmoplegia, pyramidal signs,
      extrapyramidal features, pigmentary retinopathy, peripheral neuropathy, cognitive
      dysfunction and dementia. Objective: To verify the presence of cognitive
      dysfunction among the main types of SCA described in the literature. Methods: the
      review was conducted using the search system of the PUBMED and OMIM databases.
      Results: Cognitive dysfunction occurs in a considerable proportion of SCA,
      particularly in SCA 3, which is the most frequent form of SCA worldwide. Dementia
      has been described in several other types of SCA such as SCA 2, SCA 17 and DRPLA.
      Mental retardation is a specific clinical feature of SCA 13. Conclusions: The
      role of the cerebellum in cognitive functions has been observed in different
      types of SCAs which can manifest varying degrees of cognitive dysfunction,
      dementia and mental retardation.

PMID- 29213627
TI  - Neurobiological pathways to Alzheimer's disease: Amyloid-beta, TAU protein or
      both?
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      progressive cognitive decline, including memory loss, behavioral and
      psychological symptoms and personality changes. The neuropathological hallmarks
      of AD are the presence of neuritic (senile) plaques (NP) and neurofibrillary
      tangles (NFT), along with neuronal loss, dystrophic neurites, and gliosis.
      Neuritic plaques are extracellular lesions and their main constituent is the
      amyloid-beta42 peptide (Abeta42). Neurofibrillary tangles are intracellular
      lesions that are mainly composed of hyperphosphorylated Tau protein. In this
      article, we review the major hypotheses concerning the physiopathology of AD,
      focusing on the beta-amyloid cascade as primary events (supported by the
      "betaaptists") and cytoskeletal abnormalities secondary to the
      hyperphosphorylation of protein Tau (as advocated by the "Tauists"). We further
      provide an integrative view of the physiopathology of AD.

PMID- 29213629
TI  - Physical activity and cognition in the elderly: A review.
AB  - Physical activity has been indicated as a strategy to promote health in the
      elderly, as well as to encourage the maintenance of functional capacity, and acts
      in the prevention and control of various diseases. In recent years, there has
      been great interest in studying the benefits of physical activity in the
      preservation or even improvement of cognitive performance in both the elderly
      without cognitive impairment and in elderly patients with some degree of
      cognitive impairment or dementia. The majority of epidemiological studies and
      clinical trials have evaluated aerobic exercises while few have assessed
      resistance exercise programs. The objective of this review was to examine the
      effects of different types of physical activity on cognitive function of elderly
      individuals with or without prior impairment.

PMID- 29213630
TI  - Does prevention for Alzheimer's disease exist?
AB  - The prevention of Alzheimer's disease is a growing public health concern amidst
      an ageing population. Meanwhile, there is no effective or curative treatment
      available where prevention could greatly reduce health costs. This review was
      based on reports of potential preventive factors, including modifiable lifestyle
      factors, as well as preventive pharmacological strategies. Although the present
      review was not systematic, the reports selected from PubMed using "Alzheimer's
      disease" and "prevention" as key-words, allow us to affirm that pursuing a
      healthy lifestyle; physical, cognitive, leisure activities; good social
      engagement; a high consumption of fish, low consumption of dietary fat and
      moderate consumption of wine, and control of vascular risk factors appear to be
      potential factors for delaying dementia.

PMID- 29213628
TI  - The clinical use of quantitative EEG in cognitive disorders.
AB  - The primary diagnosis of most cognitive disorders is clinically based, but the
      EEG plays a role in evaluating, classifying and following some of these
      disorders. There is an ongoing debate over routine use of qEEG. Although many
      findings regarding the clinical use of quantitative EEG are awaiting validation
      by independent investigators while confirmatory clinical follow-up studies are
      also needed, qEEG can be cautiously used by a skilled neurophysiologist in
      cognitive dysfunctions to improve the analysis of background activity, slow/fast
      focal activity, subtle asymmetries, spikes and waves, as well as in longitudinal
      follow-ups.

PMID- 29213631
TI  - Role of neuropsychological assessment in the differential diagnosis of
      Alzheimer's disease and vascular dementia.
AB  - The prevalence of dementia increases significantly from the age of 65 years,
      doubling every five years thereafter. Alzheimer's disease (AD) and vascular
      dementia (VaD) constitute the two main dementia types. Differentiating them
      encompasses anamnesis, neurological examination, laboratory and neuroimaging
      exams and neuropsychological assessment. Neuropsychological assessment produces
      different findings for each dementia type, and reveals those areas most impaired
      as well as those most preserved. The aim of the present article was to describe
      the role of neuropsychology in diagnosing dementia and achieving a differential
      diagnosis between AD and VaD. A general overview follows of the most widely known
      instruments used to assess cognitive function in dementia, and the cognitive
      changes seen in AD and VaD. The conclusion drawn was that there is significant
      overlap in cognitive changes between both these dementia types, while each type
      has its own specific characteristics which are identifiable and quantifiable on
      neuropsychological assessments and provide the basis for reaching a differential
      diagnosis.

PMID- 29213632
TI  - The ex-illiterate brain: The critical period, cognitive reserve and HAROLD model.
AB  - : The lifelong acquisition of cognitive skills shapes the biology of the brain.
      However, there are critical periods for the best use of the brain to process the
      acquired information. Objectives: To discuss the critical period of cognitive
      acquisition, the concept of cognitive reserve and the HAROLD (Hemispheric
      Asymmetry Reduction in Older adults) model. Methods: Seven women who learned how
      to read and to write after the age of 50 (ex-illiterates) and five women with 10
      years of regular schooling (controls) were submitted to a language recognition
      test while brain activity was being recorded using magnetoencephalography. Spoken
      words were delivered binaurally via two plastic tubs terminating in ear inserts,
      and recordings were made with a whole head magnetometer consisting of 148
      magnetometer coils. Results: Both groups performed similarly on the task of
      identifying target words. Analysis of the number of sources of activity in the
      left and right hemispheres revealed significant differences between the two
      groups, showing that ex-illiterate subjects exhibited less brain functional
      asymmetry during the language task. Conclusions: These results should be
      interpreted with caution because the groups were small. However, these findings
      reinforce the concept that poorly educated subjects tend to use the brain for
      information processing in a different way to subjects with a high educational
      level or who were schooled at the regular time. Finally, the recruiting of both
      hemispheres to tackle the language recognition test occurred to a greater degree
      in the ex-illiterate group where this can be interpreted as a sign of difficulty
      performing the task.

PMID- 29213633
TI  - The brain subcortical white matter and aging: A quantitative fractional
      anisotropy analysis.
AB  - : To study the integrity of hemispheric subcortical white matter by comparing
      normal young and elderly subjects using quantitative fractional anisotropy (DTI
      FA). Methods: Subjects of two different age groups (young=12, elderly=12) were
      included. MR - GE Signa Horizon - 1.5T scans were performed. Cases with Fazekas
      scores =3 were assessed on FLAIR sequence. Standard parameters for DTI-FA were
      used. ROIs were placed at various sites of the subcortical white matter, and the
      genu and splenium of the midline corpus callosum. Analysis was performed using
      Functool. Statistics for anterior and posterior white matter, as well as the genu
      and splenium were compared between the groups. The study was approved by the
      Ethics Committee of IPUB-UFRJ and informed consent obtained. Results: DTI-FA
      showed lower anisotropy values in the anterior region (subcortical white matter
      and genu), but not in the posterior region (subcortical white matter and
      splenium), in elderly normal subjects compared to young subjects. Conclusion: The
      results may represent loss of integrity of anterior (frontal) white matter fibers
      in the elderly subjects. These fibers constitute important intra- and inter
      hemispheric tracts, components of neural networks that provide cognitive,
      behavioral, motor and sensory integration. The loss of integrity of the anterior
      segments of the studied fiber systems with ageing, represents a disconnection
      process that may underlie clinical manifestations found in elderly subjects such
      as executive dysfunction.

PMID- 29213634
TI  - Visuospatial function in early Alzheimer's disease: Preliminary study.
AB  - : Alzheimer's disease (AD) is the most frequent cause of dementia, accounting for
      55% of all cases. AD patients gradually lose functional capacity, manifesting
      deficits in attention, language, temporal and direction orientation, mood,
      socialization and visuospatial function. The visuospatial function entails
      identification of a stimulus and its location. AD patients can present deficits
      in visuo-spatial skills during initial stages of the disease, but in the course
      of clinical evolution this function can become severely impaired. One of the
      neuropsychological tests indicated to evaluate the visuospatial function is the
      VOSP (The Visual Object and Space Perception Battery). Objectives: The aim of
      this preliminary study was to detect visuospatial dysfunction in early AD
      patients using the VOSP, and assess its sensitivity in a Brazilian sample.
      Results: Controls outperformed AD patients on all neuropsychological evaluations,
      except the Corsi block tapping task and cancellation task-errors. The AD patients
      performed significantly worse on all object perception and two space perception
      (Number Location and Cube Analyses) subtests of the VOSP. Conclusion: The AD
      patients demonstrated impaired visuospatial function in several aspects. The
      subtests of the VOSP were found to be sensitive for detecting this impairment in
      mild cases.

PMID- 29213635
TI  - Quality of life and Alzheimer's disease: Influence of participation in a
      rehabilitation center.
AB  - : Quality of life is seldom explored in evaluations of therapeutic interventions
      in Alzheimer's disease. Objective: To verify whether participation in a cognitive
      and functional rehabilitation program improves quality of life (QOL) among
      Alzheimer's disease (AD) patients. Methods: 19 AD patients participated in this
      study, 12 of whom attended 24 multi-professional intervention sessions - the
      experimental group - whereas the remaining 7 comprised the control group. The
      following tools were used to assess changes: a) Mini-Mental State Examination
      (MMSE); b) Geriatric Depression Scale (GDS); c) Quality of Life in AD evaluation
      scale (QOL-AD); d) Open question on QOL. Results: Participation had no positive
      impact on quantitative clinical variables (MMSE, GDS, QOL-AD). The answers to the
      open question, examined using the Collective Subject Discourse (CSD) method,
      suggested that QOL improved after the intervention. Conclusion: Combining
      pharmacological treatment with psychosocial intervention may prove to be an
      effective strategy to enhance the QOL of AD patients.

PMID- 29213636
TI  - Cognitive rehabilitation: Literature review based on levels of evidence.
AB  - The aim of this study was to review the scientific publications on cognitive
      rehabilitation in Alzheimer's disease by year published and methodology employed.
      The principles of systematic review by the Brazilian Cochrane Center were used.
      Reviews conducted by this Center were identified together with those held on the
      LILACS and Medline scientific databases. Nine levels of evidence were considered
      for analysis and a total of 37 articles were found. The results showed a growing
      number of publications from 2001 onwards, with majority being published early
      this decade. Few studies have been published on cognitive rehabilitation, with an
      average of three articles published per year during the study period (1985-2008).
      The highest levels of evidence were observed in the more recently published
      studies. Cognitive rehabilitation can yield greater benefits in rehabilitating
      patients when associated with other forms of intervention. The latest studies
      demonstrating greater scientific evidence concluded that results remain limited
      and that further studies on the topic are needed.

PMID- 29213637
TI  - The "eye sign" due to hemispatial neglect: A case report.
AB  - Conjugate eye deviation is characterized by a sustained shift in horizontal gaze,
      usually toward the affected brain hemisphere. When detected on neuroimaging, it
      is called the "eye sign". It is classically associated with lesions involving the
      frontal eye fields, ipsilateral to the side of the deviation. Neglect may be
      conceptualized as a spatially addressed bias of the sensory events in explicit
      behaviors and in the absence of perceptual and motor deficits. Hemispatial
      neglect is a common disabling condition that occurs following acute unilateral
      brain damage, usually to the right side. We report a case of a patient presenting
      with the "eye sign" on tomography, following an acute subinsular stroke, in the
      absence of conjugated eyes deviation. Our hypothesis was that the sign may have
      been due to hemispatial neglect in this patient. The aim of this article was to
      discuss the mechanisms involved in the attention network and its neuroanatomic
      correlates.

PMID- 29213638
TI  - Spreading the news: on the publication of scientific findings.

PMID- 29213639
TI  - Diffusion tensor imaging for Alzheimer's disease: A review of concepts and
      potential clinical applicability.
AB  - In view of the urgent need to identify an early and specific biomarker for
      Alzheimer's disease (AD), a PubMed database search was performed using the terms
      "Alzheimer disease" and "Diffusion Magnetic Resonance Imaging" to enable review
      of Diffusion tensor imaging (DTI) concepts and its potential clinical role in AD
      evaluation. Detailed analysis of selected abstracts showed that the main DTI
      measures, fractional anisotropy and apparent diffusion coefficient, indicators of
      fiber tract integrity, provide a direct assessment of WM fibers and may be used
      as a new biomarker for AD. These findings were found to correlate with cognitive
      assessments, rates of AD progression and were also able to differentiate among
      groups including mild cognitive impairment, AD, and other dementias. Despite
      several consistent DTI findings in AD patients, there is still a lack of
      knowledge and studies on the DTI field. DTI is not yet ready for clinical use,
      and requires extensive further research in order to achieve this goal.

PMID- 29213640
TI  - A review of Constraint-Induced Therapy applied to aphasia rehabilitation in
      stroke patients.
AB  - : Constraint-induced aphasia therapy (CIAT) is an intensive therapy model based
      on the forced use of verbal oral language as the sole channel of communication,
      while any alternative communication mode such as writing, gesturing or pointing
      are prevented. Objectives: This critical review involved the analysis of studies
      examining CIAT applied to stroke patients. Methods and Results: Using keywords,
      the Medline database was searched for relevant studies published between 2001 and
      2008 (Medline 2001-2008). The critical evaluation of the articles was based on
      the classifications described by the ASNS (Cicerone adaptation). Two studies were
      categorized as level Ia, two as level II and one study as level IV. Conclusions:
      These recommendations should be interpreted with caution, given the small number
      of studies involved, but serve as a guideline for future studies in aphasia
      therapy.

PMID- 29213641
TI  - Cognitive impairment and driving: A review of the literature.
AB  - Although some drivers with mild dementia may continue to drive after the
      condition has been diagnosed, the ability to drive a motor vehicle safely is
      eventually lost as the disease progresses. Clinicians involved in dementia care
      are often asked to make an assessment on whether a patient is fit to drive, even
      though they often lack basic knowledge and formal training in this area. The
      purpose of this review was to identify the factors that may differentiate safe
      from unsafe drivers with cognitive impairment and to discuss management
      strategies. Isolated information about staging measures or particular cognitive
      tests was found to be insufficient for decision making. Driving fitness
      counseling for patients with cognitive impairment requires a solid knowledge
      base, comprehensive assessment and thoughtful communication.

PMID- 29213642
TI  - S-TOFHLA in mild Alzheimer's disease and Mild Cognitive Impairment patients as a
      measure of functional literacy: Preliminary study.
AB  - : The greatest difficulty in diagnosing cognitive loss in our population is the
      diversity of its education which has a broad spectrum ranging from illiteracy,
      functional illiteracy and different degrees of literacy, even in those with the
      same level of schooling. Objectives: To verify whether there is impairment on the
      S-TOFHLA among individuals with AD and MCI compared with healthy controls, and to
      compare performance on the S-TOFHLA performance with neuropsychological tests and
      the scores achieved on the Raven's Colored Matrices and Vocabulary and Block
      Design (WAIS-III) as a measure of estimated intellectual level. Methods: 59
      subjects: controls (n=23; age 70.96+/-8.31y; schooling 10.2+/-5.87y; 6 men), MCI
      patients (n=11; age 74.18+/-8.12y; schooling 7.55+/-4.32y; 5 men) and AD patients
      (n=25; age 76.16+/-4.96y; schooling 7.32+/-4.78y; 10 men) were submitted to
      neuropsychological assessment, S-TOFHLA and functional evaluation. Results:
      Differences on BD, Raven and Estimated IQ were found between controls and MCI
      patients as well as controls and AD patients. On the S-TOFHLA, differences were
      found between MCI and AD patients, controls and AD patients, but not between
      control and MCI groups. S-TOFHLA performance correlated strongly with schooling
      and all neuropsychological tests, except Clock Drawing. Conclusions: The S-TOFHLA
      seems to be a useful measure for determining the level of literacy in MCI
      patients, but not in AD patients. S-TOFHLA performance was more closely
      associated with neuropsychological test scores than were years of education and
      seems to be a good predictor of level of literacy. The Vocabulary subtest proved
      to be uninfluenced by the disease process in early stages and preserved in both
      MCI and AD patients, showing that semantic memory and crystallized intelligence
      are preserved.

PMID- 29213643
TI  - Collage technique may provide new perspectives for Alzheimer patients by
      exploring messages from their inner world.
AB  - : Although the collage art technique has been introduced as a psychotherapeutic
      method, it has not been fully applied in dementia. Objectives: To analyze
      characteristics of the collage articles produced by patients with Alzheimer's
      disease (AD). Methods: Twenty AD patients were asked to select and place several
      clippings as they wished. The MMSE was used for cognitive assessments. Results:
      Simplification and poor organization in their articles were found. The themes of
      one patient were found to change according to behavior. We discussed the images
      of the articles, especially spiritual images in the early stage and family images
      in the later stage. Conclusions: We concluded that the collage technique could
      provide new perspectives for dementia patients by exploring messages from their
      inner world.

PMID- 29213644
TI  - Time of delirium onset and prognosis amongst Southern Brazilian hospitalized
      elderly patients.
AB  - : The prognostic significance of delirium in hospitalized elderly has not yet
      been fully clarified. Objectives: The present study was designed to evaluate the
      relationship between prevalent delirium (PrD), incident delirium (InD) and final
      outcome. Methods: A historical cohort of 261 patients was selected. delirium was
      diagnosed using the Confusion Assessment Method. Results: The total frequency of
      delirium detected was 42.5%-31.4% PrD and 16.2% InD. Among patients with InD, the
      average length of hospital stay was 9.1 days longer than for patients without
      delirium (p=0.002), and the hospital mortality associated with InD was 48% versus
      2.7% for those without delirium (p< 0.001). However, no difference was observed
      between patients with PrD and those without delirium. Conclusions: These results
      suggest that, when investigating delirium and prognosis amongst hospitalized
      elderly, it is fundamental to differentiate in terms of time of onset.
      Furthermore, the absence of delirium seems to be an important protective factor.

PMID- 29213645
TI  - Association between cardiovascular disease and dementia.
AB  - : Longitudinal studies have shown association between cardiovascular risk factors
      and dementia. However, these studies are not capable of detecting asymptomatic
      cardiovascular alterations and thus may provide erroneous estimates of
      association. Autopsy studies could be more useful in elucidating these questions.
      The present clinicopathological study sought to examine the relationship between
      dementia, cardiovascular risk factors and disease. Methods: 603 subjects, who
      underwent autopsy, were classified regarding the presence of dementia, according
      to post mortem cognitive classification. Demographics, cardiovascular risk
      factors, and anatomically-proven cardiovascular disease (myocardial hypertrophy,
      cerebral and carotid atherosclerosis) were compared among cognitively normal
      persons and individuals with dementia. Results: Cognitive deficit was associated
      with advanced age, stroke, physical inactivity and low body mass index (p< 0.05).
      Circle of Willis atherosclerosis was greater in patients with dementia than in
      controls on univariate analysis (p=0.01). However, this association lost
      significance when adjusted by age and gender (p=0.61). Heart failure and
      anatomopathological cardiac parameters were more severe in the control group than
      in demented individuals (p< 0.05). Carotid artery atherosclerosis and intima
      media thickness were similar in both groups. Conclusion: Advanced age, stroke,
      physical inactivity and low body mass index were linked to dementia. Circle of
      Willis atherosclerosis was associated with dementia only when age was not
      considered. Our results suggest that cerebral artery atherosclerosis was not
      directly associated with clinical expression of dementia.

PMID- 29213646
TI  - Semantic Verbal Fluency test in dementia: Preliminary retrospective analysis.
AB  - : The Semantic Verbal Fluency (SVF) test entails the generation of words from a
      given category within a pre-set time of 60 seconds. Objectives: To verify whether
      socio-demographic and clinical data of individuals with dementia correlate with
      the performance on the SVF test and to ascertain whether differences among the
      criteria of number of answers, clusters and data spread over the intervals,
      predict clinical results. Methods: This was a retrospective study of 49 charts of
      demented patients classified according to the Clinical Dementia Rating (CDR)
      scale. We correlated education, age and gender, as well as CDR and Mini-Mental
      State Exam (MMSE) scores with the number of answers, clustering and switching
      distributed over four 15-second intervals on the SVF test. Results: The
      correlation between number of answers and quartiles was weak (r=0.407, p=0.004;
      r=0.484, p< 0.001) but correlation between the number of clusters and responses
      was strong (r=0.883, p< 0.001). The number of items on the SVF was statistically
      significant with MMSE score (p=0.01) and there was a tendency for significance on
      the CDR (p=0.06). The results indicated little activity regarding what we propose
      to call cluster recalling in the two groups. Discussion: The SVF test, using
      number of items generated, was found to be more effective than classic screening
      tests in terms of speed and ease of application in patients with CDR 2 and 3.

PMID- 29213647
TI  - Brazilian caregiver version of the Apathy Scale.
AB  - : No Brazilian version of a specific scale for evaluating apathy in dementia is
      available. Objectives: To introduce a translated version of the Apathy Scale (AS)
      for use with caregivers. Methods: The instrument was formally translated and then
      administered to the caregivers of a small sample of dementia patients, in order
      to assess scale comprehensibility and make final adjustments. The scale was
      subsequently administered to the caregivers of a second, independent sample of
      Alzheimer's disease (AD) patients. The content validity of the scale was tested
      by correlating the AS scores with the Neuropsychiatric Inventory (NPI) - apathy
      sub-score and Disability Assessment in Dementia (DAD) total scores. Results: The
      first sample consisted of eleven subjects with dementia, most of whom had AD. The
      second sample comprised twenty patients with probable or possible AD (10 with
      mild dementia), a mean age of 84.1+/-5.8 years, and 2.2+/-1.6 years of schooling.
      The AS scores correlated with both NPI-apathy sub-score (r=0.756, p=0.001) and
      DAD total scores (r=-0.793, p=0.0005). Conclusions: The final version had good
      comprehensibility and correlated strongly with standardized apathy and functional
      activities of daily living measures.

PMID- 29213648
TI  - The abbreviated form of the Brief Cognitive Battery in the diagnosis of dementia
      in Alzheimer's disease.
AB  - : The Brief Cognitive Battery (BCB) developed by our group for cognitive
      assessment of low educated individuals has also shown to be highly accurate in
      diagnosing dementia of individuals with medium or high levels of education,
      making it a useful tool for populations with heterogeneous educational
      background. The application of BCB takes around eight minutes, a rather long
      period for a screening test. Objectives: Our aim was to evaluate whether the
      exclusion of items of the BCB could reduce its application time without losing
      accuracy. Methods: Patients with Alzheimer's disease with mild or moderate
      dementia (N=20), and 30 control subjects were submitted to an abbreviated version
      of the BCB in which the clock drawing test was not included as an interference
      test for the delayed recall test. Data from another 22 control individuals who
      were submitted to the original BCB in another study were also included for
      comparison. A mathematical formula was employed to compare the two versions of
      the BCB. Descriptive statistics and ROC (receiver operator characteristic) curves
      were used (alpha=0.05). Results: Using the abbreviated version, the delayed
      recall test also had high accuracy in diagnosing dementia and the mathematical
      formula results did not differ to those obtained using the original version,
      while mean time was reduced by 2 minutes and 37 seconds. Conclusions: This
      abbreviated form of the BCB is a potentially valuable tool for screening dementia
      in population studies as well as in busy clinical practices in countries with
      heterogeneous educational backgrounds.

PMID- 29213649
TI  - Accuracy of neuropsychological tests and the Neuropsychiatric Inventory in
      differential diagnosis between Frontotemporal dementia and Alzheimer's disease.
AB  - : The differential diagnosis between frontotemporal dementia (FTD) and
      Alzheimer's disease (AD) is sometimes difficult. Objectives: To verify the
      accuracy of neuropsychological tests and a behavioral disorders scale in the
      differential diagnosis between FTLD and AD. Methods: Retrospective data on 12 FTD
      patients and 12 probable AD patients were analyzed. The scores on
      neuropsychological tests (MMSE score, reverse digit span, delayed recall for
      drawings, semantic fluency of animals) and the Neuropsychiatric Inventory (NPI)
      in both groups were compared. Results: Both groups had similar performance on
      neuropsychological tests. All FTD patients and 50% of AD patients had
      neuropsychiatric abnormalities. The NPI score was 58.0+/-19.3for the FTD
      patients, and 3.6+/-4.7for the AD patients (p< 0.01). Using a NPI cut-off score
      of 13, the sensitivity and specificity were 100% in this sample. The four most
      common neuropsychiatric disturbances in FTD patients were: apathy, aberrant motor
      behavior, disinhibition and eating abnormalities. Apathy and dysphoria/depression
      were the most common behavioral symptoms among the AD patients. Conclusions: In
      this study, NPI was found to be a useful tool for the differential diagnosis
      between FTD and AD. The neuropsychological tests commonly used in the medical
      office were unable to distinguish between the two groups.

PMID- 29213650
TI  - Characteristics of falls in mild and moderate Alzheimer's disease.
AB  - : The occurrence of falls in AD patients is frequent, and their consequences are
      cognitive decline, fractures and loss of independence. Many studies have
      addressed fall risk factors in order to establish effective prevention
      strategies. Objectives: We describe the frequency and characteristics of falls in
      a sample of AD patients and their main risk factors. Methods: We evaluated 40
      subjects without cognitive impairment, and 45 AD patients, graded as CDR 1 and
      CDR 2. Results: Environmental hazard risks were the most frequent cause
      associated with falls in CDR 1 (41.4%) and CDR 2 (46.7%). Instability (31%) and
      dizziness (17.2%) were frequent causes of falls in the CDR 1 group, and this
      group showed the highest rate of recurrence (28%). In both groups of AD patients,
      indoors falls predominated (70.3 and 80% respectively for CDR 1 and 2). In our
      sample, the remaining factors studied were not associated with increasing risk
      for falls. Conclusions: These results reinforce the hypothesis that falls in AD
      are mutifactorial and that their risk factors are highly interconnected.
      Preventative strategies considering all aspects should be implemented most
      crucially eliminating environmental risks, maintaining constant presence of
      caregivers, and providing physical and functional stimulation, both in mild and
      moderate AD.

PMID- 29213651
TI  - Heterogeneity of cognitive aging in Brazilian normal elderls.
AB  - : With aging, several cognitive skills inevitably decline. However, cognitive
      losses do not occur homogenously in all elderly people, differing in number and
      severity of affected cognitive functions. These differences could be exacerbated
      by socioeconomic differences in a developing country like Brazil. Objectives: to
      characterize the cognitive functioning of healthy elderly subjects whose
      socioeconomic conditions differ to those of other studies. Methods: 60 elderly
      subjects with a mean age of 68 years, 43 women and 17 men, and mean schooling of
      7.1 years, were studied. The cognitive function of this group was assessed using
      the following neuropsychological tests: Mattis Dementia Rating Scale (MDRS),
      Stroop Test, Verbal Fluency, Wisconsin Card Sorting Test (WCST), Rey Complex
      Figure, Vocabulary - Wais - III, Logical Memory (WMS-R), Visual Reproduction (WMS
      R), and Rey Auditory-Verbal Learning Test (RAVLT). The neuropsychological data
      were submitted to Multivariate cluster analysis using SAS - Proc Cluster software
      and the complete binding hierarchical method. Results: Variability was found
      allowing classification of the studied group into 4 clusters of individuals who
      had above-average (C1), average (C3 and C4) and below average (C2) performance.
      Schooling determined the results obtained, with less educated subjects showing
      poorer performance than higher-educated subjects. Conclusions: Significant
      differences in the process of cognitive aging were detected on neuropsychological
      tests in this group of healthy elderly from the developing country of Brazil,
      where socioeconomic differences may exacerbate cognitive differences among older
      adults.

PMID- 29213653
TI  - Classification of journals in the QUALIS System of CAPES - URGENT need of
      changing the criteria!

PMID- 29213652
TI  - Non-inflammatory cerebral amyloid angiopathy as a cause of rapidly progressive
      dementia: A case study.
AB  - A 77 year-old men developed a subacute-onset, rapidly progressive cognitive
      decline. After 6 months of evolution, he scored 6 on the Mini-Mental State
      Examination and had left hemiparesis and hemineglect. The patient died 11 months
      after the onset of cognitive symptoms. Brain MRI showed microhemorrhages on
      gradient-echo sequence and confluent areas of white matter hyperintensities on T2
      weighted images. Brain biopsy revealed amyloid-beta peptide deposition in vessel
      walls, some of them surrounded by micro-bleeds. In this case report, we discuss
      the role of cerebral amyloid angiopathy (CAA) in cognitive decline, due to
      structural lesions associated with hemorrhages and infarcts, white matter lesions
      and co-morbidity of Alzheimer's disease, as well as the most recently described
      amyloid angiopathy-related inflammation.

PMID- 29213654
TI  - Vascular cognitive impairment (VCI): Progress towards knowledge and treatment.
AB  - Until recently, the study of cognitive impairment as a manifestation of
      cerebrovascular disease (CVD) has been hampered by the lack of common standards
      for assessment. The term vascular cognitive impairment (VCI) encompasses all
      levels of cognitive decline associated with CVD from mild deficits in one or more
      cognitive domains to crude dementia syndrome. VCI incorporates the complex
      interactions among classic vascular risk factors (i.e. arterial hypertension,
      high cholesterol, and diabetes), CVD subtypes, and Alzheimer's Disease (AD)
      pathology. VCI may be the earliest, commonest, and subtlest manifestation of CVD
      and can be regarded as a highly prevalent and preventable syndrome. However,
      cognition is not a standardized outcome measure in clinical trials assessing
      functional ability after stroke. Furthermore, with the exception of anti
      hypertensive medications, the impact of either preventive or acute stroke
      treatments on cognitive outcome is not known. Although clinical, epidemiological,
      neuroimaging, and experimental data support the VCI concept, there is a lack of
      integrated knowledge on the role played by the most relevant pathophysiological
      mechanisms involved in several neurological conditions including stroke and
      cognitive impairment such as excitotoxicity, apoptosis, mitochondrial DNA damage,
      oxidative stress, disturbed neurotransmitter release, and inflammation. For this
      reason, in 2006 the National Institute of Neurological Disorders and Stroke
      (NINDS) and the Canadian Stroke Network (CSN) defined a set of data elements to
      be collected in future studies aimed at defining VCI etiology, clinical
      manifestations, predictive factors, and treatment. These recommendations
      represent the first step toward developing diagnostic criteria for VCI based on
      sound knowledge rather than on hypotheses. The second step will be to integrate
      all studies using the agreed methodologies. This is likely to accelerate the
      search for answers.

PMID- 29213656
TI  - Effects of intrahippocampal administration of the phosphatase inhibitor okadaic
      acid: Dual effects on memory formation.
AB  - : Protein phosphorylation mediated by serine-threonine kinases in the hippocampus
      is crucial to the synaptic modifications believed to underlie memory formation.
      The role of phosphatases has been the focus of comparatively little study.
      Objectives: Here we evaluate the contribution of the serine-threonine protein
      phosphatases 1 and 2A (PP1, PP2A) on memory consolidation. Methods: We used
      immediate post-training bilateral hippocampal infusions of okadaic acid (OA, 0.01
      and 10 pmol/side), a potent inhibitor of PP1 and PP2A, and measured short- [3 h]
      and long-term memory [24 h] (STM, LTM) of step-down inhibitory avoidance.
      Results: At the lower dose, OA inhibited both STM and LTM whereas at the higher
      dose it instead enhanced LTM. Pre-test infusion of these two doses of OA had no
      effect on retrieval. Conclusions: These two doses of OA are known to selectively
      inhibit PP1 and PP2A respectively. These findings point to the importance of
      these enzymes in memory formation and also suggest a deleterious influence of
      endogenous hippocampal PP2A on LTM formation.

PMID- 29213655
TI  - Cognition and chronic hypoxia in pulmonary diseases.
AB  - : Lung disease with chronic hypoxia has been associated with cognitive impairment
      of the subcortical type. Objectives: To review the cognitive effects of chronic
      hypoxia in patients with lung disease and its pathophysiology in brain
      metabolism. Methods: A literature search of Pubmed data was performed. The words
      and expressions from the text subitems including "pathophysiology of brain
      hypoxia", "neuropsychology and hypoxia", "white matter injury and chronic
      hypoxia", for instance, were key words in a search of reports spanning from 1957
      to 2009. Original articles were included. Results: According to national and
      international literature, patients with chronic obstructive pulmonary disease and
      sleep obstructive apnea syndrome perform worse on tests of attention, executive
      functions and mental speed. The severity of pulmonary disease correlates with
      degree of cognitive impairment. These findings support the diagnosis of
      subcortical type encephalopathy. Conclusion: Cognitive effects of clinical
      diseases are given limited importance in congresses and symposia about cognitive
      impairment and its etiology. Professionals that deal with patients presenting
      cognitive loss should be aware of the etiologies outlined above as a major cause
      or potential contributory factors, and of their implications for treatment
      adherence and quality of life.

PMID- 29213657
TI  - Role of cognitive reserve in progression from mild cognitive impairment to
      dementia.
AB  - : Cognitive reserve is the ability to optimize performance through differential
      recruitment of brain networks, which may reflect the use of alternative cognitive
      strategies. Objectives: To identify factors related to cognitive reserve
      associated with progression from mild cognitive impairment (MCI) to degenerative
      dementia. Methods: A cohort of 239 subjects with MCI (age: 72.2+/-8.1 years, 58%
      women, education: 12 years) was assessed and followed for five years (2001 to
      2006). Results: In the first year, 13.7% of MCI converted to dementia and 34.7%
      converted within three years (78.3% converted to Alzheimer's dementia). Risk
      factors for those who converted were education less than 12 years, MMSE score
      less than 27, Boston naming test score less than 51, IQ (Intelligence Quotient)
      less than 111, age over 75 years, lack of occupation at retirement, and presence
      of intrusions in memory recall (all account for 56% of the variability of
      conversion). Conclusions: MCI patients are a population at high risk for
      dementia. The study of risk factors (e.g. IQ, education and occupation),
      particularly those related to cognitive reserve, can contribute important
      evidence to guide the decision-making process in routine clinical activity and
      public health policy.

PMID- 29213658
TI  - The Mini Mental State Examination: Review of cutoff points adjusted for schooling
      in a large Southern Brazilian sample.
AB  - : The increase in life expectancy can influence the prevalence of dementias in
      the population. Instruments that evaluate cognitive functions such as the Mini
      Mental State Examination (MMSE) are necessary for the investigation of dementia.
      The supposition that patient score on the MMSE can be influenced by academic
      level points to the need for establishing cut-off values that take into account
      educational level. The aim of this study was to review MMSE cut-off values
      adjusted for schooling in a large southern Brazilian sample. Method: Demographic
      data and MMSE scores of 968 subjects, of which 162 were dementia patients and 806
      healthy participants, were analyzed. The sample was grouped according to
      education. The cut-off values were established by ROC Curve analysis. Results:
      The total sample mean age was 70.6+/-7.3 years, and the mean years of education
      was 7.2+/-5.3. The cut-off score of 23 points (sensitivity=86%, specificity=83%)
      was observed as the optimal level to detect dementia on the MMSE instrument for
      the overall sample. Regarding level of schooling, the cut-off values were: 21 for
      the illiterate group (sensitivity=93%, specificity=82%), 22 for the low education
      group (sensitivity=87%, specificity=82%), 23 for the middle education group
      (sensitivity=86%, specificity=87%) and 24 for the high education group
      (sensitivity=81%, specificity=87%). Conclusions: The cut-off values revealed by
      this analysis, and adjusted for level of schooling, can improve the clinical
      evaluation of cognitive deficits.

PMID- 29213659
TI  - Clinical and demographic characteristics of elderly patients with dementia
      assisted at an outpatient clinic in Southern Brazil.
AB  - : The aging of the population is a worldwide phenomenon, where 60% of elders live
      in developing areas of the world such as Brazil, regions in which few studies
      have been carried out. Objectives: The goal of this study was to evaluate the
      clinical and demographic profile of patients with dementing disorders seen at a
      specialized outpatient clinic in South Brazil. Methods: A sample of 105 demented
      patients seen at the Dementia Outpatient Clinic from Hospital de Clinicas de
      Porto Alegre (HCPA), Brazil between June 2004 and June 2008. Evaluation of
      patients consisted of medical history, cognitive testing, assessment of
      functional status (Activities of Daily Living Scale - ADL; Instrumental
      Activities Daily Living - IADL) and application of the Neuropsychiatry Inventory
      (NPI) for behavioral symptoms. Severity of dementia was evaluated based on the
      CDR scale. All patients underwent laboratory screening tests and brain imaging
      exams to define etiology of dementia. Results: Of the whole sample, 71% were
      female. Age was 79+/-8 years (mean+/-SD). Educational level was 4+/-3 years
      (mean+/-SD). Sixty-four patients (60%) presented the diagnosis of Alzheimer's
      disease. Of the whole sample, 26.7% were classified as CDR=1, 44% as CDR=2 and
      29. 3% as CDR=3. A significant difference on the Mini Mental State Examination
      (MMSE) and functional status scores was observed among the CDR categories
      (severity). No significant association was found between severity and impairment
      on memory tests and behavioral symptoms. Conclusions: Alzheimer's disease was the
      most common etiology, followed by vascular dementia. At diagnosis, most patients
      presented mild to moderate severity of dementia, independent of cause.

PMID- 29213660
TI  - The influence of neuropsychiatric and functional changes on quality of life in
      Alzheimer's disease.
AB  - : To investigate the influence of neuropsychiatric manifestations and functional
      performance on quality of life (QOL) of AD patients and their caregivers/family
      members. Methods: The QOL-AD scale, Mini-Mental State Examination (MMSE),
      Geriatric Depression Scale (GDS), Cornell and Beck Scales for Depression,
      Physical and Instrumental-Self Maintenance scales (AIDL and ADL) and the
      Neuropsychiatric Inventory (NPI) were applied to 60 patients with probable AD,
      mild (n=30) or moderate (n=30) dementia, according to NINCDS-ADRDA and DSM-III-R
      criteria, respectively, and to their caregivers/family members. The total scores
      on the three QOL-AD versions were correlated with the measures previously
      mentioned. Results: The QOL-AD patients' version displayed significant
      correlations with GDS (-0.76 p<0.01), Cornell (-0.53 p<0.01) and NPI (-0.46
      p<0.05) in the mild dementia subgroup. The caregivers' version about patients'
      QOL correlated with GDS (-0.48 p<0.01), Cornell (-0.57 p<0.01), NPI (-0.46
      p<0.01) and AIDL (-0.36 p<0.05), while the caregivers' version about their own
      QOL was significantly correlated with NPI (-0.43 p<0.01), AIDL (-0.35 p<0.05) and
      Beck Depression (-0.67 p<0.01). In the moderate dementia subgroup, significant
      correlations were observed with GDS (-0.45 p<0.05) and Cornell (-0.46 p<0.01).
      For the caregivers' version about patients' QOL, significant correlations emerged
      with Cornell (-0.68 p<0.01), NPI (-0.67 p<0.01), AIDL (-0.41 p<0.05), ADL (-0.49,
      p<0.01) and Beck Depression (-0.33 p<0.05). For the caregivers' version about
      their own QOL, significant correlations with Beck Depression (-0.54 p<0.01) and
      ADL (-0.38, p<0.05) were found. Conclusion: The symptoms presented in AD affected
      the QOL in patients and caregivers/family members in both mild and moderate
      dementia.

PMID- 29213661
TI  - Subjective memory complaints in the elderly may be related to factors other than
      cognitive deficit.
AB  - : Prevalence of subjective memory complaints (SMC) in elderly community dwellers
      (ECD) ranges from 25 to 50%. Some controversy exists over the association between
      SMC and cognitive status. Objective: We investigated whether a correlation in
      cognitive performance existed between two different groups according to SMC.
      Methods: The Mini Mental State Examination (MMSE) and Dementia Rating Scale
      Mattis (DRS-Mattis) were applied to two groups: ECD (n=14) with SMC and residents
      (n=14) of a long-term care facility (LTCF) without SMC. Results: The median age
      in the ECD group was 81.0 years, and in the LTCF group was 75.0 years. There was
      a statistically significant difference (p=0.048) between these groups regarding
      age. Concerning schooling (1-8 or >=9 years), there was no statistically
      significant difference between the groups (p=0.638). No statistically significant
      difference between the two groups was found for scores on the cognitive tests.
      Conclusion: SMC might be related to extrinsic factors other than insipient
      cognitive decline.

PMID- 29213662
TI  - Phonological analysis of substitution errors of patients with apraxia of speech.
AB  - : The literature on apraxia of speech describes the types and characteristics of
      phonological errors in this disorder. In general, phonemes affected by errors are
      described, but the distinctive features involved have not yet been investigated.
      Objective: To analyze the features involved in substitution errors produced by
      Brazilian-Portuguese speakers with apraxia of speech. Methods: 20 adults with
      apraxia of speech were assessed. Phonological analysis of the distinctive
      features involved in substitution type errors was carried out using the protocol
      for the evaluation of verbal and non-verbal apraxia. Results: The most affected
      features were: voiced, continuant, high, anterior, coronal, posterior. Moreover,
      the mean of the substitutions of marked to markedness features was statistically
      greater than the markedness to marked features. Conclusions: This study
      contributes toward a better characterization of the phonological errors found in
      apraxia of speech, thereby helping to diagnose communication disorders and the
      selection criteria of phonemes for rehabilitation in these patients.

PMID- 29213663
TI  - The relationship between severity of apraxia of speech and working memory.
AB  - : Based on previously observed relationships between working memory (WM) and
      speech, the current study investigated the relationship between degree of oral
      apraxia (AOS) and WM capacity. Methods: This study involved assessment and
      classification of degree of apraxia of speech in 22 apraxic participants and
      evaluation of WM capacity using digit span and word-list repetition tests. Both
      tests were able to assess the phonoarticulatory loop, while the Rey Auditory
      Verbal Learning Test investigated the phonoarticulatory loop and the episodic
      buffer. Results: Independently from the degree of apraxia of speech, all of
      participants presented compromise in WM. Conclusions: The data presented might
      suggest that individuals with AOS typically have WM impairment, but it is still
      not clear if the severity of AOS is related to WM capacity. Future studies could
      verify the relationship between the severity of apraxia and the severity of WM
      deficits.

PMID- 29213664
TI  - Efficacy and safety of brand-risperidone versus similar-risperidone in elderly
      patients with neuropsychiatric disorders: A retrospective study.
AB  - : To compare the efficacy and tolerability of brand-risperidone against similar
      risperidone in elderly outpatients. Method: The medical files of 16 elderly
      outpatients from the IPq-HCFMUSP treated with two formulations of risperidone
      (brand and similar) between July/1999 and February/2000 were reviewed. Two
      independent raters, using the Clinical Global Impression scale, evaluated the
      efficacy of the treatment with risperidone and the frequency of adverse effects.
      Results: Comparing October/1999 to November/1999, Rater 1 observed a trend
      (p=0.059) and Rater 2 found a statistically significant difference, in favor of
      the brand-risperidone group (p=0.014). Comparing October/1999 to February/2000,
      Rater 1 observed no statistically significant difference (p=0.190), but the Rater
      2 found a statistically significant difference in favor of the brand-risperidone
      group (p=0.029). Comparing November/1999 to February/2000, both raters found no
      statistically significant differences between both risperidone formulations.
      Regarding adverse effects, a statistically significant difference (p=0.046) was
      found in favor of the patients treated with brand-risperidone. Conclusions: The
      risperidone-reference, compared to similar-risperidone, showed a trend toward
      greater efficacy and tolerability.

PMID- 29213665
TI  - Progressive posterior cortical dysfunction.
AB  - Progressive posterior cortical dysfunction (PPCD) is an insidious syndrome
      characterized by prominent disorders of higher visual processing. It affects both
      dorsal (occipito-parietal) and ventral (occipito-temporal) pathways, disturbing
      visuospatial processing and visual recognition, respectively. We report a case of
      a 67-year-old woman presenting with progressive impairment of visual functions.
      Neurologic examination showed agraphia, alexia, hemispatial neglect (left side
      visual extinction), complete Balint's syndrome and visual agnosia. Magnetic
      resonance imaging showed circumscribed atrophy involving the bilateral parieto
      occipital regions, slightly more predominant to the right. Our aim was to
      describe a case of this syndrome, to present a video showing the main
      abnormalities, and to discuss this unusual presentation of dementia. We believe
      this article can contribute by improving the recognition of PPCD.

PMID- 29213667
TI  - In the June 2010 issue.

PMID- 29213666
TI  - Dementia in Fragile X-associated Tremor/Ataxia Syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a cause of movement
      disorders and cognitive decline which has probably been underdiagnosed,
      especially if its prevalence proves similar to those of progressive supranuclear
      palsy and amyotrophic lateral sclerosis. We report a case of a 74-year-old man
      who presented with action tremor, gait ataxia and forgetfulness. There was a
      family history of tremor and dementia, and one of the patient's grandsons was
      mentally deficient. Neuropsychological evaluation disclosed a frontal network
      syndrome. MRI showed hyperintensity of both middle cerebellar peduncles, a major
      diagnostic hallmark of FXTAS. Genetic testing revealed premutation of the FMR1
      gene with an expanded (CGG)90 repeat. The diagnosis of FXTAS is important for
      genetic counseling because the daughters of the affected individuals are at high
      risk of having offspring with fragile X syndrome. Tremors and cognitive decline
      should raise the diagnostic hypothesis of FXTAS, which MRI may subsequently
      reinforce, while the detection of the FMR1 premutation can confirm the condition.

PMID- 29213668
TI  - Cognitive impairment in clinically isolated syndrome: A systematic review.
AB  - : The pattern of cognitive abnormalities in multiple sclerosis (MS) has been
      extensively studied and well characterized. However, little is known about the
      cognitive involvement in patients with the clinically isolated syndrome (CIS).
      Objectives: To perform a systematic review of the results of the studies on
      cognitive dysfunction in CIS patients. Methods: Cochrane, Lilacs, PubMed/Medline
      and SciELO databases were searched for studies involving patients with clinically
      isolated syndrome submitted to neuropsychological evaluation. Results: Seven
      studies fulfilled the selection criteria adopted in this review. The pattern of
      cognitive abnormalities in CIS resembles that found in patients with MS and is
      characterized by attention deficit, reduced information processing speed and
      impaired working memory and executive functions. The frequency of cognitive
      impairment in CIS seems to be lower than in MS. Conclusions: Cognition should be
      evaluated in patients with CIS. Future studies are required to evaluate the
      impact of cognitive abnormalities and to correlate them with axonal damage
      findings in patients with CIS.

PMID- 29213669
TI  - Episodic memory, concentrated attention and processing speed in aging: A
      comparative study of Brazilian age groups.
AB  - : Neuropsychological studies on the processing of some specific cognitive
      functions throughout aging are essential for the understanding of human cognitive
      development from ages 19 to 89. Objectives: This study aimed to verify the
      occurrence of differences in the processing of episodic memory, concentrated
      attention and speed of attentional processing among four age groups of adults.
      Methods: A total of 136 neurologically healthy adults, aged 19-89, with 9 or more
      years of schooling, took part in the study. Participants were divided according
      to four age groups: young, middle-aged, elderly and oldest old adults. Subtests
      of the Brief Neuropsychological Evaluation Instrument (NEUPSILIN) were applied
      for the cognitive assessment. Mean score of corrected answers and of response
      times were compared between groups by means of a one-way ANOVA test with post-hoc
      Scheffe procedures and ANCOVA including the co-variables of years of schooling
      and socio-economical scores. Results: In general, differences in performance were
      observed from 60 years old on. Only the episodic memory task of delayed recall
      reflected differences from the age of around 40 onwards and processing speed from
      around the age of 70 onwards. Thus, differences were found between the age groups
      regarding their cognitive performance, particularly between young adults and
      elderly adults, and young adults and oldest old adults. Conclusions: Our research
      indicates that the middle-aged group should be better analyzed and that
      comparative cross-sectional studies including only extreme groups such as young
      and elderly adults are not sufficient.

PMID- 29213670
TI  - Analysis of error type and frequency in apraxia of speech among Portuguese
      speakers.
AB  - : Most studies characterizing errors in the speech of patients with apraxia
      involve English language. Objectives: To analyze the types and frequency of
      errors produced by patients with apraxia of speech whose mother tongue was
      Brazilian Portuguese. Methods: 20 adults with apraxia of speech caused by stroke
      were assessed. The types of error committed by patients were analyzed both
      quantitatively and qualitatively, and frequencies compared. Results: We observed
      the presence of substitution, omission, trial-and-error, repetition, self
      correction, anticipation, addition, reiteration and metathesis, in descending
      order of frequency, respectively. Omission type errors were one of the most
      commonly occurring whereas addition errors were infrequent. These findings
      differed to those reported in English speaking patients, probably owing to
      differences in the methodologies used for classifying error types; the inclusion
      of speakers with apraxia secondary to aphasia; and the difference in the
      structure of Portuguese language to English in terms of syllable onset complexity
      and effect on motor control. Conclusions: The frequency of omission and addition
      errors observed differed to the frequency reported for speakers of English.

PMID- 29213671
TI  - Distinct attitudes of professionals from different medical specialties toward
      autonomy and legal instruments in the assessment of patients with Alzheimer's
      disease.
AB  - : The evaluation of competence of Alzheimer's disease (AD) patients to assume
      personal or collective responsibilities and the resulting legal implications is a
      relevant issue. Objectives: The aim of this study was to evaluate the attitudes
      of different medical specialists towards the disability of patients with
      Alzheimer's disease and practitioners' competence to interfere with decision
      making autonomy. Methods: Professionals from different areas (Neurology,
      Psychiatry, Geriatrics, and General Practice) were interviewed by one of the
      authors, after being presented a fictitious clinical case which raised several
      topics, namely:[1] Critical judgment and capacity of the patient to take
      decisions related to daily activities;[2] The role of family physicians in
      nominating trustees and caregivers. Results: Answers to the first question did
      not differ regarding degree of preservation of awareness but at least 25%
      stressed that the patient must be carefully listened to, independent of caregiver
      or legal representative opinion. There were significant knowledge gaps in
      responses to the second question. Half of the physicians interviewed did not have
      adequate information about the legal aspects of caring for patients with
      Alzheimer's disease. Conclusions: Legal aspects is a topic that must be
      incorporated into professional training in order to improve attitudes toward the
      long-term management of patients with dementia.

PMID- 29213672
TI  - Correlation between hippocampal volumes and proton magnetic resonance
      spectroscopy of the posterior cingulate gyrus and hippocampi in Alzheimer's
      disease.
AB  - : Prior studies have reported hippocampal volume loss, decrease in N
      Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration
      in patients with Alzheimer's disease (AD). The purpose of this study was to
      evaluate hippocampal volumes of AD patients and their correlation with metabolic
      changes detected by proton spectroscopy (1H MRS) of hippocampal formations and
      the posterior cingulate region. Materials and Methods: 22 patients with probable
      AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were
      enrolled in the study. Hippocampal volumetric measurements, single-voxel 1H MRS
      of the posterior cingulate region and of hippocampal formations were obtained.
      The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA.
      Statistical analysis was performed to detect differences and correlations between
      these parameters in patients and controls. Results: The hippocampal volume of
      patients and controls did not differ significantly. The results of 1H MRS
      differed significantly between patients and controls in the hippocampal
      formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr,
      mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate
      region, having a sensitivity of 0.899 and specificity of 0.800. There was no
      correlation between hippocampal volumes and the results of 1H MRS in patients
      with AD. Conclusions: The results of 1H MRS differed significantly between
      patients and controls in hippocampal formations and the posterior cingulate
      region, with NAA/Cr proving to be the best predictor for AD. No correlation
      between hippocampal volumes and the results of 1H MRS in patients with AD was
      observed.

PMID- 29213673
TI  - Effects of cognitive training based on metamemory and mental images.
AB  - : There is scant research evidence regarding training effects among elderly with
      limited educational experience. Research indicating an association between
      metamemory and memory performance is based on samples of older adults with at
      least 12 years of education. Objectives: To test the efficacy of a cognitive
      training program based on the creation of mental images and changes in specific
      aspects of metamemory in individuals with 3 to 15 years of education (M=8.38,
      SD=4.24). Methods: 37 older adults participated in five training sessions
      (Training Group (TG)) and 32 control subjects completed only pre and post test
      assessments (Control Group (CG)) including the Mini Mental Status Examination
      (MMSE), the Geriatric Depression Scale (GDS), the Brief Cognitive Screening
      Battery (BCSB)(naming and memorization of 10 pictures, animal category verbal
      fluency test, the Clock Drawing Test (CDT)), the Story subtest from the Rivermead
      Behavioural Memory Test (RBMT), the Memory Complaint Questionnaire (MAC-Q), and
      the Picture and Story domains from the Memory Self-Efficacy Questionnaire (MSEQ).
      Results: The TG showed significant improvement between pre and post tests on the
      delayed recall of the 10 pictures and in self-efficacy for the memorization of
      stories. These same changes were not found in the CG. Conclusions: Five-session
      cognitive training may lead to significant improvements in episodic memory and
      memory self-efficacy, an aspect of metamemory, in individuals with an average of
      8 years of education.

PMID- 29213674
TI  - Mini-Mental State Examination among lower educational levels and illiterates:
      Transcultural evaluation.
AB  - : Cognitive performance among illiterates and low educational levels is poorer
      than that observed in individuals with greater schooling. This difference can be
      a confounding factor in reaching an accurate diagnosis of cognitive impairment.
      In addition, there is great heterogeneity in performance among illiterates,
      probably due to different environmental demands and sociocultural backgrounds.
      Many reports have described the influence of education on neuropsychological
      measures and screening tests such as the Mini-Mental State Examination (MMSE).
      Objectives: To analyze performance in two samples with the same educational
      level, but different social and cultural backgrounds. Methods: Subjects from two
      different locations in Brazil (rural sample from Northern region and urban sample
      residing in the largest city of the Southeastern region) were matched for age and
      education, and submitted to the MMSE. Results: Significant differences between
      the groups were found in total scores on the MMSE and in temporal orientation and
      serial-sevens sub-items for which the urban sample performed best but analysis of
      illiterates alone yielded the same results, except for the copying pentagons task
      which was performed better by the rural sample. Conclusions: Cultural and social
      backgrounds, as well as demands from the environment, influence results of
      screening tests. Factors other than education must be taken into account when
      analyzing tests.

PMID- 29213675
TI  - The influence of schooling on performance in the Mattis Dementia Rating Scale
      (DRS).
AB  - : Studies have shown the influence of schooling on performance in the Dementia
      Rating Scale (DRS), suggesting that a single cut-off score is not appropriate for
      all groups of elderly people. Objectives: To verify the influence of schooling on
      the DRS in a Brazilian elderly population. Methods: The DRS was applied to 118
      cognitively healthy controls and to 97 patients with mild probable Alzheimer's
      disease (AD). In order to analyze the influence of education, patients and
      controls were divided into four groups of schooling (GRSC): GRSC 1 with 1 to 4
      years of schooling, GRSC 2 with 5 to 8 years of schooling, GRSC 3 with 9 to 11
      years of schooling, and GRSC 4 with more than 11 years of schooling. Results: In
      the intragroup analysis, the performance of controls within each schooling group
      was compared, revealing a significant difference on total score and the subscales
      Attention, I/P and Conceptualization. The same procedure was used for the AD
      patients and a significant difference was observed for total score and the
      subscales Attention, Construction, Conceptualization and Memory. In the
      intergroup analysis, the results on total DRS and for the I/P, Conceptualization
      and Memory subscales showed significant differences in GRSC 1, 2, 3 and 4. The
      Attention subscale showed differences in GRSC 3 and 4, and on the Construction
      subscale in GRSC 1 and 4. Conclusions: The results highlight the importance of
      norms for the DRS in the Brazilian population that take into account the effects
      of schooling on the scores of this scale.

PMID- 29213676
TI  - Parkinson's disease: Impact of clinical and cognitive aspects on quality of life.
AB  - : Parkinson's disease (PD) is a chronic disease manifested principally by motor
      signs and symptoms, but with frequent neuropsychological alterations. Objectives:
      To study the relationship between clinical and cognitive aspects and the
      perception of quality of life (QOL) in PD patients. Methods: Twenty consecutive
      patients (13 men) with idiopathic PD (mean age: 64.5y), mean disease time of 7.8
      years and at stages 1-3 according to the modified Hoehn and Yahr staging scale
      (HYS), all outpatients from the Neurology Department of the Celso Pierro General
      and Maternity Hospital (PUC-Campinas), were analyzed. The following were applied:
      a clinical-neurological assessment, the Mini-Mental State Examination (MMSE),
      standard neuropsychological battery of the CERAD (Consortium to Establish a
      Registry for Alzheimer's Disease), Hamilton Depression Rating Scale (HAM-D) and a
      QOL questionnaire (Parkinson's Disease Questionnaire - PDQ-39). Statistical
      analysis was carried out at a significance level of p<0.05. Results: On the PDQ
      39 under the sections total, mobility and activities of daily living, and the
      items motor compromise (HYS) and language of the MMSE were predictors of worse
      QOL. Verbal fluency was a factor for emotional well-being on the PDQ-39, whereas
      higher scores for HAM-D and worse performance on the item attention and
      calculation of the MMSE were associated with worse QOL in the social support
      section. Total score on the MMSE and educational level were QOL factors in
      cognition. Conclusions: The findings of the present study suggest that clinical,
      cognitive, motor or other depression-related factors contribute differently to
      the domains of QOL.

PMID- 29213679
TI  - In the September 2010 issue.

PMID- 29213678
TI  - Oral infections and orofacial pain in Alzheimer's disease: Case report and
      review.
AB  - Dental infections, frequent in the general population, are a common cause of
      inflammation with systemic impact, and are the most common cause of orofacial
      pain. Temporomandibular disorders are also frequent in the elderly and represent
      an important cause of secondary headache. Both inflammation and pain can also
      contribute to cognitive, functional and behavioral impairment of the elderly and
      aggravate symptoms of patients with Alzheimer's disease (AD). We report a case of
      a 74-year-old woman with AD and chronic facial pain who had a significant
      improvement in functional activities as well as in cognition and depressive
      symptoms after successful treatment of her facial pain. Patients with AD have
      higher compromise of oral health with infections and teeth loss. The
      investigation of orofacial pain should be performed in patients with AD, because
      of the associations reviewed and given the potential for improvement as
      highlighted by this case.

PMID- 29213677
TI  - Post-Mortem diagnosis of dementia by informant interview.
AB  - : The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of
      the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an
      informant. Objectives: To ascertain the sensitivity and specificity of postmortem
      diagnosis based on informant interview compared against the diagnosis established
      at a memory clinic. Methods: A prospective study was conducted at the BBBABSG and
      at the Reference Center for Cognitive Disorders (RCCD), a specialized memory
      clinic of the Hospital das Clinicas, University of Sao Paulo Medical School.
      Control subjects and cognitively impaired subjects were referred from the
      Hospital das Clinicas to the RCCD where subjects and their informants were
      assessed. The same informant was then interviewed at the BBBABSG. Specialists'
      panel consensus, in each group, determined the final diagnosis of the case, blind
      to other center's diagnosis. Data was compared for frequency of diagnostic
      equivalence. For this study, the diagnosis established at the RCCD was accepted
      as the gold standard. Sensitivity and specificity were computed. Results: Ninety
      individuals were included, 45 with dementia and 45 without dementia (26
      cognitively normal and 19 cognitively impaired but non-demented). The informant
      interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for
      the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7%
      for the diagnosis of normal cognition. Conclusions: The informant interview used
      at the BBBABSG has a high specificity and sensitivity for the diagnosis of
      dementia as well as a high specificity for the diagnosis of normal cognition.

PMID- 29213680
TI  - Illiteracy and dementia.
AB  - There is a current concept that illiteracy and lower educational levels are risk
      factors for cognitive decline and dementia. Our aims were to review the
      association between illiteracy and dementia; and to describe some results on
      neuropsychological findings in illiteracy. A literature search of the PubMed
      database was performed. The search terms were "dementia", "illiteracy",
      "neuropsychological evaluation", "educational levels", and "education". Only
      papers published in Portuguese, English, and Spanish were reviewed. Illiteracy is
      an incontestable risk factor for dementia. It influences performance on almost
      cognitive tests. Many other factors could be connected to the high prevalence of
      dementia among illiterates: low cognitive reserve, poor control of
      cerebrovascular disease risk factors, difficulties in cognitive evaluation, and
      poor adaptation of neuropsychological tests for this specific population.
      Functional tests must be coupled with cognitive tests to ameliorate diagnostic
      accuracy.

PMID- 29213681
TI  - Severe dementia: A review about diagnoses, therapeutic management and ethical
      issues.
AB  - North American data show that in the year 2000 around 4.5 million people had a
      diagnosis of dementia and more than a half were at moderate or severe stages of
      the disease. There is inevitable cognitive and functional decline caused by all
      etiologies of irreversible dementia as well as many behavioral symptoms that
      compromise the quality of life of both patients and caregivers. Few published
      studies have investigated issues concerning severe dementia such as predictors of
      mortality and life expectancy, nutrition, end of life issues and palliative care
      in terminal dementia, as well as best pharmacological and non-pharmacological
      treatments. Due to the complexity that characterizes advanced dementia, it is
      important that this discussion starts as early as possible allowing some
      decisions to be taken, preferably when the patients can still express their
      opinion.

PMID- 29213682
TI  - Reviewing the limb apraxia concept: From definition to cognitive
      neuropsychological models.
AB  - Apraxia is a disorder of learned skilled movements, in the absence of elementary
      motor or sensory deficits and general cognitive impairment such as inattention to
      commands, object-recognition deficits or poor oral comprehension. The first
      studies on apraxia were performed between the late 19th and early 20th centuries,
      however controversy remains in praxis literature concerning apraxia types,
      neuroanatomical and functional correlates, as well as assessment and treatment of
      apraxia. Thus, a critical review of the literature was conducted searching the
      literature for evidence contributing to a more detailed description of apraxia
      and its clinical patterns, physiopathology and clinico-anatomical correlations,
      as well as apraxia assessment.

PMID- 29213683
TI  - History, citoarchitecture and neurophysiology of human and non human primates'
      parietal lobe: A review.
AB  - This strict localizationism had and still has its importance for the development
      of Neurosciences, since the analysis of changes in mental processes resulting
      from brain damage became the basis for understanding the brain organization. The
      human parietal cortex is a highly differentiated structure, consisting of
      citoarchitectonically defined subareas that are connected to other cortical and
      subcortical areas. Patients with lesions in the parietal cortex develop various
      types of neuropsychological manifestations, depending on the specific location of
      the lesion and the corresponding hemisphere and these lesions in this lobe do not
      cause modal specific disturbances. The establishment of homologies between the
      parietal region in humans and primates can be of great contribution in trying to
      unravel the various functions and complexity of this area.

PMID- 29213684
TI  - The prefrontal areas and cerebral hemispheres of the neotropical Cebus apella and
      its correlations with cognitive processes.
AB  - : The organization of the prefrontal cortex can hold important clues to
      understanding its functioning. The Cebus apella present cerebral particularities
      and behavioral and cognitive flexibility, possessing abilities that demonstrate
      an overlap with those of big primates. Objectives: To provide evidence of
      correlations between anatomical particularities of the brain areas analyzed and
      some cognitive abilities previously described in these simians. Methods: The
      relative size of the cerebral hemispheres and prefrontal areas (PFA) were
      measured using a Universal caliper, in 24 hemispheres of C. apella fixed with 10%
      formaldehyde and kept in 70% alcoholic solution. Results: Data gathered allowed
      the calculation of the approximate volume (cm3) of the areas under study: right
      antimere 35.2cm3 (+/-5.3), left antimere 31.3cm3 (+/-5.4) and of the left PFA
      6.0cm3 (+/-1.5) and right PFA 6.9cm3 (+/-1.7). Conclusions: We concluded that the
      PFA represents about 20% of the cerebral volume of this primate. No significant
      differences were found in the antimeres in terms of volume and area of the
      hemispheres and likewise for the PFA. These animals have a proportionally bigger
      brain than that of other neotropical primates in the literature. This allows us
      to infer that the frontal lobe of C. apella is also larger; possibly related to
      its maturity and developed cognitive functions indicative of the culture
      transfers characteristic of this species.

PMID- 29213685
TI  - Apathy in Alzheimer's disease: Contribution to a clinical view on progression of
      dementia.
AB  - : In addition to cognitive impairment, apathy is increasingly recognized as an
      important neuropsychiatric syndrome in Alzheimer's disease (AD). Aims: To
      identify the relationship between dementia severity and apathy levels, and to
      discuss the association of this condition with other psychopathological
      manifestations in AD patients. Methods: This study involved 15 AD patients (mean
      age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia,
      living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive
      status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global
      Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale
      and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological
      manifestations such as depression were also considered. Results: Patients with
      more severe dementia presented higher levels of apathy, reinforcing the
      hypothesis that apathy severity aggravates as the disease progresses. Using the
      Spearman coefficient correlation an association was identified between the MMSE
      and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI
      apathy domain (r=0.81; p=0.01). Associations were also found between the Global
      Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the
      Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01). Conclusions:
      Apathy is a distinct syndrome among patients with AD and increases with global
      deterioration.

PMID- 29213686
TI  - The generation of visual inferences in normal elderly- Influence of schooling and
      visual complexity.
AB  - : The generation of inferences makes the construction and comprehension of
      discourse easier, and integrates representations which add coherence to the
      arguments. Visuoperceptual and inferential deficits merge in the attempt to
      explain the difficulties that some individuals have in the comprehension of
      certain kinds of visual stimuli. Objectives: a) To examine the performance of
      cognitively healthy elderly subjects in the execution of visual inferences using
      pictures of different levels of complexity;b) To compare the performance of
      subjects according to schooling level. Methods: A total of 45 normal elderly aged
      from 61 to 82yrs (M=68; SD=0.57) were examined. The subjects were divided into
      three groups according to schooling level: Group 1 (1 to 4 years); Group 2 (5 to
      8 years) and Group 3 (9 or more years). Each subject had to create a narrative
      based on four figures with controlled visual complexity. The narratives were
      transcribed, analysed and scored. Results: For the essential inferences, the high
      educated group (3) had a better performance in both visually simple and complex
      conditions. On the visually complex figures, the medium educated group (2) was
      statistically equivalent to the high educated group for one figure and equivalent
      to the less educated group (1) for the other. There was no difference among the
      groups for the accessory propositions. Conclusions: Visual complexity interferes
      with the subject's ability to make inferences in low and medium educated
      individuals. High educated subjects maintain the same performance in making
      inferences, regardless of the visual complexity level.

PMID- 29213687
TI  - Verbal behavior in Alzheimer's disease patients: Analysis of phrase repetition.
AB  - : Language problems in the elderly with AD are due to the fact that deterioration
      occurs not only in semantic memory, but in a group of cognitive factors,
      evidenced by a deficiency in search strategies for linguistic information.
      Objectives: To evaluate phrase repetition in two cognitive tests, the MMSE and
      MoCA, in a group of Alzheimer disease patients (AD) and normal controls. Methods:
      A Cross-sectional study was conducted involving 20 patients who sought medical
      assistance at a geriatric institute in Jundiai, Sao Paulo. The subjects underwent
      a detailed clinical examination and neuropsychometric evaluation. All subjects
      with AD met DSM-IV and NINCDS-ADRDA criteria. Ten patients received a diagnosis
      of AD and 10 were healthy subjects, forming the control group (CG). Results: All
      participants correctly answered the phrase from the MMSE (phrase 1). The MoCA
      phrases (phrases 2 and 3) were correct in 80% and 90%, respectively in the CG and
      in 40% and 50%, respectively in the AD group. Conclusions: The MoCA test proved
      more effective in evaluating the echoic behavior in AD patients compared to the
      MMSE. The simpler phrase repetition task in the MMSE was found to be less
      sensitive in detecting mild language decline in AD patients.

PMID- 29213688
TI  - Criterion validity of a Wechsler-III Scale Short Form in a sample of brazilian
      elderly.
AB  - : Although a normative process, changes in cognitive functioning vary among older
      adults. The differential diagnosis between normal and pathological aging must be
      made early using psychometrically adequate measures. Objectives: To assess the
      evidence of criterion validity of a Short Form (SF) of the Wechsler-III Scale
      containing eight subtests (SF8) by determining its sensitivity, specificity,
      positive and negative predictive values and cut-off points for Brazilian elderly
      from different age groups. Methods: 168 individuals, aged 60 years or above,
      living in the community or in an institution, were assigned to case and control
      groups, and investigated according to age range. Measures included a
      sociodemographic questionnaire, the Mini-Mental State Examination (MMSE), Verbal
      Fluency Test, Clock-Drawing Test and the SF8. Results: More than two thirds of
      the sample was women (73.8%), mean age was 74.5 years (SD=8.9), mean education
      was 6.2 years (SD=4.8) and 40.5% were widows/widowers. In the total sample, the
      best cut-off point for the SF8 was 142 while cut offs among individuals aged 60
      to 69 years, 70 to 79 years, and more than 80 years were 160, 129 and 129,
      respectively. Conclusions: The results demonstrated the importance of different
      cut-off points for different age ranges. Sensitivity and specificity values of
      the SF8 were sufficiently high to warrant the use of the SF8 as an instrument to
      identify cognitive impairment in the elderly.

PMID- 29213689
TI  - Longitudinal cognitive screening study in community-dwelling individuals.
AB  - : Cognitive changes in normal aging can be similar to the alterations that take
      place in the initial stages of a dementia process. Longitudinal studies can
      provide a better understanding of this progression. Objectives: To evaluate the
      cognitive and functional evolution of community-dwelling individuals without
      dementia through a three-year longitudinal study. Methods: 168 individuals were
      evaluated in 2006. Three years later in 2009, 73 of these subjects were
      reevaluated as regards cognition and functionality using the Mini Mental State
      Examination (MMSE), Brief Cognitive Battery (BCB) and the Pfeffer Functional
      Activities Questionnaire. The statistical analysis included descriptive
      measurements, the Wilcoxon's test for intra-group comparison, and the Spearman's
      correlation coefficient test for comparing cognitive and functionality scores.
      Results: After three years, the Wilcoxon's test showed a discreet yet significant
      cognitive decline (MMSE: -0.7 points; p=0.02; Z= -2.29; and global score on the
      BCB: +3.6 points; p=0.02; Z= -2.29), in addition to functional decline (Pfeffer:
      +0.7 points; p= 0.001; Z= -3.38). Conclusions: After three years of follow-up we
      observed a discreet yet significant functional and cognitive decline in the
      subjects. Longitudinal cognitive screening represents an important strategy in
      the early identification of changes from normal conditions to a dementia process.

PMID- 29213690
TI  - Working memory intervention programs for adults: A systematic review.
AB  - : This systematic review aimed to identify the designs, procedures, and results
      of empirical studies that performed neuropsychological interventions on WM in
      adults. Methods: A PubMed and LILACS literature search was conducted using the
      keywords working memory AND (training OR rehabilitation OR intervention) AND
      adult. Results: Of the seven studies found, three were randomized controlled
      trials, two were case reports, one was a clinical trial, and one was an
      evaluation study. With regard to the type of programs and samples, three studies
      employed global programs with healthy elderly adults and four employed specific
      programs for samples with neurologically-impaired adults. Conclusions: The
      effectiveness of the WM intervention programs was more evident in studies that
      employed specific methods of rehabilitation for samples with neurological
      disorders than in those based on global programs with healthy adults. There is a
      need for more empirical studies to verify the effectiveness of WM intervention
      programs in order to provide adequate guidance for clinical neuropsychologists
      and future research.

PMID- 29213691
TI  - Sociodemographic profile and level of burden of dementia patients' caregivers who
      participate in a support group.
AB  - : The Brazilian Alzheimer's Association recommend the dementia patient's
      caregiver to attend group meetings which aim to give information and enable them
      to express and share feelings with individuals who are facing similar
      difficulties. Objectives: To identify the sociodemographic profile of the
      individuals who attend the Support Group for Family Members of Individuals with
      Alzheimer's disease at Hospital de Clinicas de Porto Alegre, and to verify the
      degree of burden associated to the care given to this kind of patient. Methods:
      Forty-eight participants were sub-divided into two groups: 23 non-caregivers and
      25 caregivers. All participants answered a sociodemographic questionnaire, and
      the caregivers also answered the Zarit Burden Interview (ZBI). Student's t test
      was used for comparison of parametric data, and Chi-square test for categorical
      data between caregivers and non-caregivers. Spearman's rho correlation analysis
      was performed for the ZBI and the studied variables. Results: Participants were
      predominantly women. Only age differentiated one subgroup from the other. The
      mean score on the ZBI was 35.1 (14.7), and most of the caregivers presented up to
      moderate burden. Conclusions: Women attended the Support Group either as
      caregiver or non-caregiver. The level of burden among caregivers of high
      educational attainment was relatively high besides the short time as caregiver
      (up to a year).

PMID- 29213692
TI  - Caregiver distress associated with behavioral and psychological symptoms in mild
      Alzheimer's disease.
AB  - : The aim of this study was to analyze the relationship between Caregiver
      Distress and Behavioral and Psychological Symptoms in Dementias (BPSD) in mild
      Alzheimer's disease. Methods: Fifty patients and caregivers were interviewed
      using the Neuropsychiatric Inventory (NPI). Results: 96.0% of the patients had at
      least one BPSD. The mean NPI total score was 19.6 (SD=18.05; range=0-78) whereas
      the mean Caregiver Distress Index (CDI) total score was 11.5 (SD=10.41; range=0
      40). For the individual symptoms, the weighted mean CDI was 2.8 (SD=1.58). All
      symptom CDI means were higher than 2.0 except for euphoria/elation (m=1.8;
      SD=1.49). There were correlations between CDI and derived measures (Frequency,
      Severity, FxS, and Amplitude) for all symptoms, except Disinhibition and Night
      time behavior. Correlations ranged between 0.443 and 0.894, with significance at
      p<0.05. Conclusions: All the derived measures, including amplitude, were useful
      in at least some cases. The data suggests that CDI cannot be inferred from
      symptom presence or profile. Symptoms should be systematically investigated.

PMID- 29213693
TI  - A prospective study on the use of rivastigmine transdermal patch in Alzheimer's
      dementia in a routine clinical setting.
AB  - : There is not much published literature on the use of rivastigmine patch in a
      "routine" clinical setting. Objectives: In this naturalistic longitudinal
      observational study we sought to evaluate the safety, tolerability and efficacy
      of the rivastigmine patch in patients with early and late onset moderate
      Alzheimer's disease in a routine clinical setting. Methods: Out of all routine
      clinical referrals, the first 30 patients with diagnosis of moderate Alzheimer's
      dementia who were started on rivastigmine patch were included in the study.
      Rivastigmine patch dose was titrated from 4.6 to 9.5mg/24 hours as appropriate.
      The primary outcome measure was safety and tolerability, measured by the
      incidence of adverse events and discontinuation due to any reason. The secondary
      outcome measure was to examine improvement on global, functional and behavioral
      domains as demonstrated by the MMSE (Mini Mental State Examination) score, BADLS
      (Bristol Activities of Daily Living Skills) score, patient and carer feedback and
      clinical judgment. Results: Adverse events were reported in 20% of patients and
      10% of total patients needed discontinuation of treatment. Improvement on global,
      functional and behavioral domains was observed in two thirds of patients whereas
      one third showed a relative decline. The most common side effect was skin
      irritation or erythema. Conclusions: The rivastigmine transdermal patch may
      provide a treatment option for those patients who require a change in their
      current oral cholinesterase inhibitor therapy due to safety or tolerability
      concerns.

PMID- 29213695
TI  - In the December 2010 issue.

PMID- 29213694
TI  - Air traffic control activity increases attention capacity in air traffic
      controllers.
AB  - : Air traffic controllers simultaneously develop complex and multiple tasks in
      the course of their activities. In this context, concern is raised over the high
      level of attention needed by these professionals which can ultimately be affected
      by stress and fatigue. Objectives: The objective of this study was to assess
      attention level in air traffic controllers (ATCo). Methods: 45 flight protection
      professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten
      or more years in the profession (ATCo>=10, n=15) and ATCo with less than ten
      years in the profession (ATCo <10, n=15) and 15 aeronautical information services
      operators (AIS), subdivided into AIS with ten years or more in the profession
      (AIS>=10, n=8) and AIS with less than ten years in the profession (AIS <10, n=7),
      who were included as the control group. The digit symbol, d2 (the individual
      marks the letter d on a specific form containing 14 lines with 47 letters in
      each, maintaining focus on letter d followed by two dashes), forward digit span,
      backward digit span and PASAT (paced auditory serial addition test) attention
      tests were used. Kruskal-Wallis was used and data expressed as Median (Minimum
      and Maximum) with p<0.05. Results: The ATCo>=10 presented greater focus of
      attention, sustained attention, mental manipulation and resistance to
      interference capacity compared to the AIS>=10. Comparison of ATCo>=10 to the
      AIS<10 showed they presented only greater resistance to interference, and when
      compared to the ATCo<10 presented lower focus. Conclusions: The air traffic
      control activity after ten years may be associated with a high level of
      attention.

PMID- 29213696
TI  - Preclinical diagnosis of Alzheimer's disease: Prevention or prediction?
AB  - The diagnosis of Alzheimer's disease (AD) for cases with dementia may be too late
      to allow effective treatment. Criteria for diagnosis of preclinical AD suggested
      by the Alzheimer's Association include the use of molecular and structural
      biomarkers. Preclinical diagnosis will enable testing of new drugs and forms of
      treatment toward achieving successful preventive treatment. But what are the
      advantages for the individual? To know that someone who is cognitively normal is
      probably going to develop AD's dementia when there is no effective preventive
      treatment is definitely not good news. A research method whereby volunteers are
      assigned to receive treatment or placebo without knowing whether they are in the
      control or at-risk arm of a trial would overcome this potential problem. If these
      new criteria are used wisely they may represent a relevant milestone in the
      search for a definitive treatment for AD.

PMID- 29213697
TI  - The economic cost of Alzheimer's disease: Family or public health burden?
AB  - Alzheimer's disease (AD) patients suffer progressive cognitive, behavioral and
      functional impairment which result in a heavy burden to patients, families, and
      the public-health system. AD entails both direct and indirect costs. Indirect
      costs (such as loss or reduction of income by the patient or family members) are
      the most important costs in early and community-dwelling AD patients. Direct
      costs (such as medical treatment or social services) increase when the disorder
      progresses, and the patient is institutionalized or a formal caregiver is
      required. Drug therapies represent an increase in direct cost but can reduce some
      other direct or indirect costs involved. Several studies have projected overall
      savings to society when using drug therapies and all relevant cost are
      considered, where results depend on specific patient and care setting
      characteristics. Dementia should be the focus of analysis when public health
      policies are being devised. South American countries should strengthen their
      policy and planning capabilities by gathering more local evidence about the
      burden of AD and how it can be shaped by treatment options.

PMID- 29213698
TI  - Methodological issues and controversies in research on cognitive disorders.
AB  - Research on cognitive disorders is challenging due to the complexity of functions
      studied and to the numerous variables involved. First, the concept of cognition
      as a mediated (semiotic) and systemic activity is reviewed. According to this
      concept, the result of a local lesion is not an isolated symptom but a syndrome,
      and the best neuropsychological approach is an analysis based on appropriate
      tests to disclose double dissociations and thereby provide clues to brain
      behavior relationships. This approach takes into account the influence of task
      relevant variables (confounders) related to the patient (e.g., age, education),
      to the lesion (size, etiology), and to the tests and testing conditions
      (ecological validity, examiner's experience), which need to be controlled and
      analyzed in multivariate statistical analyses, as illustrated in research on
      medial temporal lobe epilepsy. Other controversial issues such as single and
      double dissociations, single-case versus group studies, and the lesion method are
      also examined.

PMID- 29213699
TI  - Musical training, neuroplasticity and cognition.
AB  - The influence of music on the human brain has been recently investigated in
      numerous studies. Several investigations have shown that structural and
      functional cerebral neuroplastic processes emerge as a result of long-term
      musical training, which in turn may produce cognitive differences between
      musicians and non-musicians. Musicians can be considered ideal cases for studies
      on brain adaptation, due to their unique and intensive training experiences. This
      article presents a review of recent findings showing positive effects of musical
      training on non-musical cognitive abilities, which probably reflect plastic
      changes in brains of musicians.

PMID- 29213700
TI  - Naming abilities: Differentiation between objects and verbs in aphasia.
AB  - Cognitive Neuropsychology aims to understand the processing mechanisms of normal
      and injured brain, by means of functional architectural models of information
      processing. Naming is one of the most important abilities in linguistic
      processing. Naming of different semantic and grammatical categories differ in
      their lexical properties and have distinct neuroanatomical substrates. We
      reviewed literature data on the differences between nouns and verbs in aphasic
      subjects reported by scientific publications in the form of indexed articles.
      Studies on naming abilities tended to emphasize the differentiation between nouns
      and verbs both in their lexical properties and neuroanatomical substrates.
      Functional neuroimaging studies have improved the state of knowledge regarding
      category-specific naming abilities, but further studies on different types of
      aphasia and the use of naming abilities in different contexts are warranted.

PMID- 29213701
TI  - Cerebrocerebellar system and Arnold's bundle - A tractographic study: preliminary
      results.
AB  - : The cerebellum, traditionally considered a structure involved in balance and
      movement control, was more recently recognized as important in cognitive,
      emotional and behavioral functions. These functions appear to be related to the
      more recent parts of the cerebellum that belong to the cerebrocerebellar system.
      One of the key segments of this system is the (pre)fronto-[penduncule]-pontine
      projection that represents the Arnold's bundle. Diffusion tensor imaging and
      tractography (DTI-TR) has permitted in vivo virtual dissection of white matter
      tracts, including those of the cerebellar. Objective: To study the fronto
      [peduncule]-pontine projection (Arnold's bundle), with DTI-TR. Methods: Ten
      normal subjects were included (mean age 30 years). Standard acquisitions in three
      planes were obtained with a 1.5T GE Signa Horizon scanner, complemented with DTI
      acquisitions. Post-processing and analysis was performed using an ADW 4.3
      workstation running Functool 4.5.3(GE Medical Systems). A single ROI was placed
      on the medial third of the cerebral peduncle base, considered the site of
      convergence of the fibers of Arnold's bundle, bilaterally. Results: Twenty
      tractograms were obtained. All were constituted by a significant number of fibers
      in correspondence to the frontal lobe, and part of them anterior to the coronal
      plane at the anterior commissure, which characterizes them as associated to the
      prefrontal region. Conclusions: For the first time, frontal lobe related
      projections were systematically revealed with DTI-TR seeded from cerebral
      peduncle base ROIs. They showed anatomic coherence with Arnold's bundle, which
      includes the prefrontopontine segment of the cortico-ponto-cerebellar path, one
      of the components of the cerebrocerebellar system, acknowledged as fundamental
      for non-motor functions such as cognition, emotion and behavior.

PMID- 29213702
TI  - Kanji and Kana agraphia in mild cognitive impairment and dementia: A trans
      cultural comparison of elderly Japanese subjects living in Japan and Brazil.
AB  - : This study verifies the environmental effects on agraphia in mild cognitive
      impairment and dementia. We compared elderly Japanese subjects living in Japan
      and Brazil. Methods: We retrospectively analyzed the database of the Prevalence
      Study 1998 in Tajiri (n=497, Miyagi, Japan) and the Prevalence Study 1997 of
      elderly Japanese immigrants living in Brazil (n=166, migrated from Japan and
      living in the Sao Paulo Metropolitan Area). In three Clinical Dementia Rating
      (CDR) groups, i.e., CDR 0 (healthy), CDR 0.5 (questionable dementia), and CDR 1+
      (dementia) , the Mini-Mental State Examination (MMSE) item of spontaneous writing
      and the Cognitive Abilities Screening Instrument (CASI) domain of dictation were
      analyzed with regard to the number of Kanji and Kana characters. Formal errors in
      characters and pragmatic errors were also analyzed. Results: The immigrants in
      Brazil wrote similar numbers of Kanji or Kana characters compared to the
      residents of Japan. In spontaneous writing, the formal Kanji errors were greater
      in the CDR 1+ group of immigrants. In writing from dictation, all the immigrant
      CDR groups made more formal errors in Kana than the Japan residents. No
      significant differences in pragmatic errors were detected between the two groups.
      Conclusions: Subjects living in Japan use Kanji frequently, and thus the form of
      written characters was simplified, which might be assessed as mild formal errors.
      In immigrants, the deterioration in Kanji and Kana writing was partly due to
      decreased daily usage of the characters. Lower levels of education of immigrants
      might also be related to the number of Kanji errors.

PMID- 29213703
TI  - Rehabilitation in semantic dementia: Study of effectiveness of lexical
      reacquisition in three patients.
AB  - : Although language rehabilitation in patients with primary progressive aphasia
      (PPA) is recommended, rehabilitation studies in this clinical syndrome are
      scarce. Specifically, in relation to semantic dementia (SD), few studies have
      shown the possibility of lexical relearning. Objective: To analyze the
      effectiveness of rehabilitation for lexical reacquisition in SD. Methods: Three
      SD patients were submitted to training for lexical reacquisition based on
      principles of errorless learning. Comparisons between naming performance of
      treated items (pre and post-training) and non-treated items of the Boston Naming
      Test (BNT) were made. Results: All patients improved their performance in naming
      treated words after intervention. However, decline in performance in naming of
      non-treated items was observed. Case 1 named zero items at baseline while her
      performance post-training was 29.4% correct responses without cueing, and 90.7%
      correct with and without cueing. Case 2 named 6.9% of items correctly at baseline
      and his performance in post-training was 52.9% without cueing and 87.3%, with and
      without cueing. Case 3 named zero items at baseline and his performance in post
      training was 100% correct responses without cueing. Considering the performance
      in naming the non-treated items of the BNT, the percentages of correct responses
      in the first evaluation and in the re-evaluation, respectively were: 16.7% and
      8.3% (case 1; 14 month-interval); 26.7% and 11.6% (case 2; 18 month-interval) and
      11.6% and 8.3% (case 3; 6 month-interval). Conclusions: The reacquisition of lost
      vocabulary may be possible in SD despite progressive semantic deterioration.

PMID- 29213704
TI  - Body mass index, cognitive deficit and depressive symptoms in high cardiovascular
      risk patients.
AB  - : To evaluate the relationship of obesity, cognitive impairment and depressive
      symptoms in patients with high cardiovascular risk. Methods: A sample of 93
      patients aged 50 years or older was selected from the Center of Dyslipidemia and
      High Cardiovascular Risk from Hospital de Clinicas de Porto Alegre (HCPA).
      Patients with stroke were excluded. For cognitive evaluation, the MMSE (Mini
      Mental State Examination) was used. A score of 24 or less was considered as
      cognitive impairment, and for those who had 4 years or less of education, the
      cutoff point was 17. The GDS-15 (Geriatric Depression Scale) was also used, with
      the cutoff of 6 for presence of depressive symptoms. Results: Obese patients
      showed lower mean MMSE scores compared to non-obese patients (p=0.0012).
      Additionally, for every one point increase in BMI above 30 there was a 27%
      increase in the chances of the patient having cognitive impairment. The obese
      patients presented 31% chance of having cognitive impairment compared with
      overweight subjects. Conclusions: Our findings corroborated the association
      between obesity and cognitive impairment in high cardiovascular risk patients.
      This association however, was not observed for depressive symptoms.

PMID- 29213705
TI  - Intelectual demand and formal education as cognitive protection factors in
      Alzheimer's disease.
AB  - : To investigate the possible association between educational level and previous
      professional occupation, and objective cognitive and functional evaluation in a
      sample of elderly patients with Alzheimer's disease. Methods: Through
      retrospective analysis of medical files, 174 patients with probable Alzheimer
      disease were randomly selected, classified and submitted to analysis according to
      previous professional occupation and years of formal education. Results: Subjects
      with lower education and less intellectually-demanding occupations performed
      worse than higher educated subjects in all cognitive subtests and on the
      functional scale. Conclusions: Results indicate that not only the total years of
      education, but also professional occupation has an impact on cognition and
      functioning in accordance with the hypothesis of cognitive reserve. Our findings
      confirmed this hypothesis, where subjects with higher education/ higher
      intellectual demand manifested first symptoms later than low education/ low
      intellectual demand subjects, with the latter group also exhibiting faster
      disease progression.

PMID- 29213706
TI  - Stress effects on food handlers' attention of a public hospital in Recife-PE,
      Brazil.
AB  - : Production of meals in Food and Nutrition Units (FNU) requires human labor
      performance in order to attend demand. Stress is one of the factors responsible
      for alterations in the health of these professionals. Reduced attention is one of
      the negative effects caused by stress. Objective: The objective of this study was
      to evaluate attention in Food Handlers (FH). Methods: 67 professionals were
      evaluated, subdivided into FH with less than 5 years in the profession, who were
      included as the control group (Control, n=29), and FH with more than 5 years in
      the profession (FH>5, n=38). Lipp's Inventory of Stress Symptoms for adults
      (LISS), the digit symbol, d2, forward digit span, backward digit span and paced
      auditory serial addition tests were applied. The data found on the LISS were
      analysed by Fisher's Exact and Chi-Square tests and individual attention tests
      were analyzed by the Mann-Whitney test, with data expressed as Median (Minimum
      and Maximum) with p<0.05. A total of 73.68% of FH>5 presented stress versus
      13.79% of Control. Also, 57.89% of FH>5 with stress presented physical symptoms
      and 15.79% psychological symptoms. In the Control, 9.68% presented physical
      symptoms. Results: 73.68% of FH>5 with stress and 17.24% of the Control were in
      the resistance phase. Regarding attention, the FH>5 presented reduced focused
      attention (32.5+/-2.9), auditory attention (7.25+/-0.4) and resistance to
      interference (4.67+/-1.1), compared to their respective controls (43.88+/-1.39),
      (8.63+/-0.38), (9.25+/-1.16), p<0.05. Discussion and Conclusions: The activity of
      food handling can cause stress and attention level reduction after 5 years.

PMID- 29213707
TI  - Morphometric brain changes during aging: Results from a Brazilian necropsy
      sample.
AB  - : The present study aimed to establish the morphometric brain changes during
      aging in a necropsy series from Brazil and determine whether sexual dimorphisms
      interfere in these changes. Methods: A cross-sectional study was conducted at the
      Sao Paulo Autopsy Service in Brazil where, after informed consent, data was
      gathered from next of kin interview with reference to clinical status prior to
      death. Brain weight, volume and density measurements were taken and then adjusted
      for head circumference. Descriptive statistics and tests of hypothesis and
      correlations were applied, considering a p-value of 0.05. Results: 414 subjects,
      mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain
      weight of the sample was 1219.2g+/-140.9and mean volume was 1217mL+/-152.3. The
      mean brain density of the sample was 1.0g/mL+/-0.09. Values differed between
      males and females in terms of weight and volume. Brain weight decreased during
      aging by about 45g per decade (r= -0.300; p<0.01) and volume by about 43mL (r= 
      0.278; p<0.00). Mean density of the sample was 1.0 g/mL in both genders.
      Conclusions: Brain weight and volume (with or without corrections) decreased
      during aging, and these reductions were more pronounced in women. Density
      remained unchanged for both genders. Further studies are needed to investigate
      factors associated to these reductions.

PMID- 29213708
TI  - Did you rule out neurosyphilis?
AB  - : Neurosyphilis, formerly a frequent cause of dementia, is now a rare condition
      in developed countries. However, syphilis remains common in many developing
      countries, where adequate diagnosis and treatment of early syphilis may be
      lacking, increasing the chances of neurosyphilis and prevalence of syphilitic
      dementia. Objectives: To present cases of syphilitic dementia seen in a cognitive
      and behavioral neurology unit in Brazil, emphasizing their first symptoms and the
      challenges they posed in diagnosis. Methods: At our unit of the Hospital das
      Clinicas of the University of Sao Paulo, all patients are submitted to blood
      treponemal tests. When the test is positive, a lumbar puncture is performed. We
      retrospectivelly reviewed all cases of neurosyphilis seen in our unit from
      January 1991 to November 2009. Results: Nine cases of neurosyphilis (0.77% of the
      1160 cases in our files) were identified over the period. Patients with
      neurosyphilis were all men, had a mean age of 47.8 (+/-13.0) years (median of 43
      years), and presented with various neuropsychiatric syndromes and elusive
      diagnoses. The median time from onset of symptoms to diagnosis was 24 months and
      only one patient made a full recovery after treatment. Conclusions: Neurosyphilis
      is not frequent but remains present, causing several types of neuropsychiatric
      syndromes. As it is very simple to rule out neurosyphilis by performing a blood
      treponemal test, this test should be performed in all patients with
      neuropsychiatric symptoms, particularly in regions of the world where syphilis is
      still a commonly occurring disease.

PMID- 29213709
TI  - Impact of depressive symptoms in outcome of Alzheimer's disease.
AB  - : There is no consensus in the medical literature about the impact of depressive
      symptoms on the evolution of Alzheimer's disease (AD). Objective: To compare the
      evolution of AD patients, with and without depressive symptoms, in terms of
      cognition, functionality and caregiver stress. Methods: The study entailed 2
      stages: an initial retrospective stage involving review of medical charts of
      patients with mild and moderate AD. Patients were divided according to the
      presence or absence of depressive symptoms, defined by medical interview and
      questions on depressed mood from the CAMDEX (Cambridge Examination for Mental
      Disorders of the Elderly) and Neuropsychiatric Inventory (NPI). Twenty-nine
      patients were evaluated, 37.9% with depression (Group D+) and 62.1% without
      depression (Group D-). The groups were compared regarding demographic and medical
      characteristics, cognitive and functional performance, presence of apathy as a
      separate symptom, and caregiver stress, using standardized tests and
      questionnaires. In the second transversal step, the same tools were reapplied
      after 2 to 4 years of follow-up, and evolution for the two groups was compared.
      Results: The two groups were highly homogeneous in demographic and clinic
      characteristics, as well as in length of follow-up, and presented no significant
      difference in cognitive or functional evaluation at the time of diagnoses or
      after follow-up. Only caregiver stress was greater in Group D+ at the two time
      points (p<0.001). Conclusions: No differences in the evolution of AD patients
      with or without depressive symptoms were evident. Nevertheless, these symptoms
      were associated to emotional burden of caregivers.

PMID- 29213710
TI  - Multiple hallucinations due to brainstem injury: A case report.
AB  - We report a case of a 43-year-old woman with brainstem encephalitis in the third
      trimester of pregnancy. She presented complex visual and auditory hallucinations
      in the acute disease phase (hearing opera arias and seeing room furniture upside
      down). Hallucinations resolved with antiviral treatment.

PMID- 29213712
TI  - In the March 2011 issue.

PMID- 29213713
TI  - Path dependence in social and psychological risk factors for dementia.
AB  - This article focuses on social and psychological risk factors for Alzheimer's
      disease, dementia, and cognitive impairment and presents some key points for
      prevention in developing countries based on previous studies, a social science
      theory, and our preliminary survey. Previous population-based studies found that
      educational and occupational attainment, income, participation in social and
      mental activities, and psychological distress were associated with dementia risk.
      According to the theory of path dependence, earlier factors largely determine
      successive ones, where education is one of these early experiences in life. Our
      preliminary survey suggested that education sets a path that several psychosocial
      risk factors are dependent on. The expansion of basic education is indispensable.
      Resources for prevention should be concentrated on individuals with a low level
      of education. In order to break from a path creating self-reinforcement of risk
      factors, it is necessary to implement early and active interventions.

PMID- 29213715
TI  - Cognitive rehabilitation following traumatic brain injury.
AB  - Annually, some 500,000 people are hospitalized with brain lesions acquired after
      traumatic brain injury (TBI) in Brazil. Between 75,000 and 100,000 individuals
      die within hours of the event and 70,000 to 90,000 evolve to irreversible loss of
      some neurological function. The principal causes of TBI include motor vehicle
      accidents (50%), falls (21%), assaults and robberies (12%) and accidents during
      leisure activities (10%). Within this context, cognitive rehabilitation, a
      clinical area encompassing interdisciplinary action aimed at recovery as well as
      compensation of cognitive functions altered as a result of cerebral injury, is
      extremely important for these individuals. Therefore, the aim of this study was
      to review the basic concepts related to TBI, including mechanisms of injury,
      severity levels of TBI, the most common findings in moderate and severe TBI
      survivors, and the most frequent cognitive impairments following TBI, and also to
      discuss the strategies used to handle patients post-TBI. The study results
      yielded relevant information on a structured cognitive rehabilitation service,
      representing an alternative for patients and families afflicted by TBI, enabling
      the generation of multiple research protocols.

PMID- 29213716
TI  - Formal education, health literacy and Mini-Mental State Examination.
AB  - : The Mini-Mental State Examination (MMSE) is a widely used screening test for
      cognitive impairment, but is heavily biased by education. Educational level has
      frequently been ranked using years of schooling, which may not be a good indirect
      measure of educational level because there is great heterogeneity in standards of
      schooling among populations and across regions of the same country. S-TOFHLA is a
      measure of health literacy with some results indicating that it is a good measure
      for literacy level. Objective: To evaluate the correlations between years of
      schooling and scores on the S-TOFHLA and the MMSE. Methods: Healthy subjects
      without cognitive impairment were submitted to the S-TOFHLA and the MMSE.
      Correlations and regression analysis were performed to determine possible
      associations among variables. Results: Both years of schooling and S-TOFHLA
      scores were strongly correlated with MMSE scores, but the strongest association
      was reached by the S-TOFHLA (r=0.702, p<0.01), where the S-TOFHLA was the best
      predictor of MMSE scores (R2=0.494, p<0.001). Conclusions: A stronger association
      between S-TOFHLA scores and MMSE performance was found than between years of
      education and MMSE scores. This finding justifies further studies incorporating
      years of schooling together with S-TOFHLA score, to evaluate cognitive
      performance.

PMID- 29213714
TI  - Effects of stress hormones on the brain and cognition: Evidence from normal to
      pathological aging.
AB  - Several studies have demonstrated a wide cognitive variability among aged
      individuals. One factor thought to be associated with this heterogeneity is
      exposure to chronic stress throughout life. Animal and human evidence
      demonstrates that glucocorticoids (GCs), the main class of stress hormones, are
      strongly linked to memory performance whereby elevated GC levels are associated
      with memory performance decline in both normal and pathological cognitive aging.
      Accordingly, it is believed that GCs may increase the brain's vulnerability to
      the effects of internal and external insults, and thus may play a role in the
      development of age-related cognitive disorders such as Alzheimer's disease (AD).
      The aim of this review article was to investigate the effects of GCs on normal
      and pathological cognitive aging by showing how these hormones interact with
      different brain structures involved in cognitive abilities, subsequently worsen
      memory performance, and increase the risk for developing dementia.

PMID- 29213717
TI  - The interpretation of proverbs by elderly with high, medium and low educational
      level: Abstract reasoning as an aspect of executive functions.
AB  - : It is now known that cognitive functions tend to decline with age. Executive
      functions (EF) are among the first abilities to decline with aging. A
      subcomponent of the EF is abstract reasoning. The Test of Proverbs is an
      instrument that can be used to evaluate the capacity of abstract reasoning.
      Objective: To examine the association of performance in interpretation of
      proverbs, with education and with episodic memory and EF tasks. Methods: A total
      of 67 individuals aged between 60 and 75 years were evaluated, and divided into
      three categories of education: 1-4 years, 5-8 years, and 9 or more years of
      schooling. The instruments used were a sociodemographic questionnaire (gender,
      age, marital status, education, income, previous occupation, current occupation
      and health perception), the Mini Mental State Examination, Brief Cognitive
      Screening Battery; Geriatric Depression Scale; Forward and Backward Digit Span
      (WAIS-III), and the Test of Proverbs. Results: A high impact of education was
      seen on the interpretation of proverbs, with lower performance among the elderly
      with less education. A significant association between performance on the Test of
      Proverbs and scores on the MMSE, GDS, and verbal fluency tests was found. There
      was a modest association with incidental memory. Conclusions: The capacity to
      interpret proverbs is strongly associated with education and with performance on
      other EF tasks.

PMID- 29213718
TI  - Antipsychotics in Alzheimer's disease: A critical analysis.
AB  - : The estimated worldwide prevalence of dementia among adults older than 60 years
      of age was 3.9% in 2005. About 90% of demented patients will develop
      neuropsychiatric symptoms (NS) such as delirium, delusion, aggressiveness and
      agitation. The treatment of NS involves non-pharmacologic strategies (with
      varying degrees of success according to the scientific literature) and
      pharmacologic treatment (PT). The present review of literature examined the
      current role of AP in the management of NS in dementia. Methods: A thematic
      review of medical literature was carried out. Results: 313 articles were found,
      39 of which were selected for critical analysis. Until 2005, the best evidence
      for PT had supported the use of selective serotonin re-uptake inhibitors (SSRIs),
      anticholinesterases, memantine and antipsychotics (AP). In 2005, the U.S. Food
      and Drug Administration (FDA) disapproved the use of atypical APs to treat
      neuropsychiatric symptoms in individuals with dementia (the same occurred with
      the typical APs in 2008). After this, at least two important randomized placebo
      controlled multicenter trials were published examining the effectiveness of
      atypical APs in Alzheimer's disease (CATIE-AD) and the effects of interrupting AP
      treatment (DART-AD). Conclusions: Based on the current evidence available, APs
      still have a place in treatment of the more serious psychotic symptoms, after the
      failure of non-pharmacological treatment and of an initial approach with
      selective inhibitors of serotonin uptake, anticholinesterases and memantine.

PMID- 29213719
TI  - Prevalence of treatable and reversible dementias: A study in a dementia
      outpatient clinic.
AB  - : Dementia is a syndrome characterized by the development of multiple cognitive
      deficits and behavioral changes that leads to impairment of functional
      activities. There are primary degenerative, progressive and irreversible
      dementias, and other dementias resulting from a progressive but potentially
      reversible dementia of secondary origin. Objective: To assess the prevalence of
      cases with a diagnosis of potentially reversible dementia at a Behavioral
      Neurology Outpatient Unit. Methods: A retrospective study based on a review of
      340 medical records of patients seen from 1999 to 2009 was conducted. All
      patients received a thorough diagnostic assessment to verify the etiological
      hypothesis proposed. Results: Of the 340 patients seen in the study period, 172
      (50.5%) were females and 168 (49.5%) males, 90 patients (26.4%) were under 60
      years of age, and 250 (73.6%) were over 60 years of age. Alzheimer's disease,
      with 89 cases (26%), followed by vascular dementia with 39 cases (11.47%), were
      the leading etiological diagnoses. A total of 193 patients had dementia and 37 of
      these (19.17%) were found to have potentially reversible dementias, distributed
      as follows: head injury: 15 patients; alcohol-related dementias: 11 patients;
      meningoencephalitis: 2 patients; hypothyroidism: 2 patients; neurosyphilis: 2
      patients; normal pressure hydrocephalus: 2 patients; AIDS: 1 patient; Korsakoff's
      syndrome: 1 patient, and Post-anoxic dementia: 1 patient. Conclusions: A
      significant number of patients were found to have potentially reversible
      dementias (19.17%). These data show an urgent need for more extensive diagnostic
      investigation, and indicate the possibility of reversing some dementias,
      especially cases detected early.

PMID- 29213720
TI  - Cognitive training based on metamemory and mental images: Follow-up evaluation
      and booster training effects.
AB  - : In the second semester of 2008, 37 seniors participated in five cognitive
      training sessions based on creation of imagery and modification of self-efficacy
      for memory tasks. Objective: To carry out a follow-up evaluation after 18 months
      in order to detect possible maintenance of gains reported in the first post-test,
      namely, in measures of self-efficacy and episodic memory, and to evaluate the
      impact of a training booster, that is, test whether there are additional gains
      when training is offered for the second time to the same participants. Methods:
      16 older adults agreed to participate in five training sessions for the second
      time. Participants were evaluated with the Mini Mental Status Examination - MMSE,
      the Geriatric Depression Scale - GDS, the Brief Cognitive Screening Battery -
      BCSB (naming and memorization of 10 pictures, animal category verbal fluency
      test, the Clock Drawing Test - CDT), the Story subtest from the Rivermead
      Behavioural Memory Test - RBMT, the Memory Complaint Questionnaire - MAC-Q, and
      the Picture and Story domains from the Memory Self-Efficacy Questionnaire - MSEQ
      used to evaluate the effectiveness of the first intervention. Results: This study
      reports the maintenance of the effects generated by the original training
      conducted in 2008, and follow-up evaluations detected the presence of potential
      additional gains in some aspects of memory. Conclusions: Training boosters may
      help maintain cognitive stability in adulthood and old age.

PMID- 29213721
TI  - Congenital prosopagnosia: A case report.
AB  - Prosopagnosia is a visual agnosia characterized by an inability to recognize
      previously known human faces and to learn new faces. The aim of this study was to
      present a forty-six year-old woman with congenital prosopagnosia, and to discuss
      the neural bases of perception and recognition of faces. The patients had a
      lifetime impairment in recognizing faces of family members, close friends, and
      even her own face in photos. She also had impairment in recognizing animals such
      as discriminating between cats and dogs. The patient's basic visual skills showed
      impairment in identifying and recognizing the animal form perception on the
      coding subtest of the WAIS-R, recognizing overlapping pictures (Luria), and in
      identifying silhouettes depicting animals and objects (VOSP). Unconventional
      tests using pictures evidenced impairment in her capacity to identify famous
      faces, facial emotions and animals. Her face perception abilities were preserved,
      but recognition could not take place. Therefore, it appears that the agnosia in
      this case best fits the group of categories termed "associative".

PMID- 29213722
TI  - Trichotillomania in a dementia case.
AB  - We report an 87-year-old male case of hair pulling associated with a white-matter
      vascular dementia (Binswanger's disease). Trichotillomania in our case did not
      resolve using mirtazapine or anticholinesterasic medication. Trichotillomania
      seems to be related to a form of perseveration associated with dementia. The
      findings in this case suggest the abnormality involving white matter in the
      pathogenesis of trichotillomania, may constitute a defect in connectivity in the
      right frontal-subcortical circuit.

PMID- 29213723
TI  - Brief reviews.

PMID- 29213724
TI  - In the June 2011 issue.

PMID- 29213725
TI  - Prospective memory in Alzheimer's disease and Mild Cognitive Impairment.
AB  - Prospective memory (PM) is defined as remembering to carry out intended actions
      at an appropriate point in the future, and can be categorized into three types of
      situation: time-, event-, and activity-based tasks. PM involves brain structures
      such as frontal and medial temporal cortices. The aim of this study was to review
      the currently available literature on PM in Alzheimer's disease and Mild
      Cognitive Impairment patients. We performed a search on Pubmed, Medline, ScieLO,
      LILACS and the Cochrane Library electronic databases from January 1990 to
      December 2010. The key terms used were: prospective memory, memory for
      intentions, delayed memory and memory for future actions, separately and also
      combined with the search terms dementia, Alzheimer's disease and Mild Cognitive
      Impairment. Both patient groups showed significant impairment in PM. Further
      studies are needed to verify the accuracy of PM tasks as an early marker of mild
      cognitive impairment, and initial dementia.

PMID- 29213726
TI  - Neural correlates of lexical-semantic memory: A voxel-based morphometry study in
      mild AD, aMCI and normal aging.
AB  - : Neuroanatomical correlations of naming and lexical-semantic memory are not yet
      fully understood. The most influential approaches share the view that semantic
      representations reflect the manner in which information has been acquired through
      perception and action, and that each brain area processes different modalities of
      semantic representations. Despite these anatomical differences in semantic
      processing, generalization across different features that have similar semantic
      significance is one of the main characteristics of human cognition. Methods: We
      evaluated the brain regions related to naming, and to the semantic
      generalization, of visually presented drawings of objects from the Boston Naming
      Test (BNT), which comprises different categories, such as animals, vegetables,
      tools, food, and furniture. In order to create a model of lesion method, a sample
      of 48 subjects presenting with a continuous decline both in cognitive functions,
      including naming skills, and in grey matter density (GMD) was compared to normal
      young adults with normal aging, amnestic mild cognitive impairment (aMCI) and
      mild Alzheimer's disease (AD). Semantic errors on the BNT, as well as naming
      performance, were correlated with whole brain GMD as measured by voxel-based
      morphometry (VBM). Results: The areas most strongly related to naming and to
      semantic errors were the medial temporal structures, thalami, superior and
      inferior temporal gyri, especially their anterior parts, as well as prefrontal
      cortices (inferior and superior frontal gyri). Conclusion: The possible role of
      each of these areas in the lexical-semantic networks was discussed, along with
      their contribution to the models of semantic memory organization.

PMID- 29213727
TI  - Performance of Brazilian children on phonemic and semantic verbal fluency tasks.
AB  - : The most used verbal fluency paradigms are semantic and letter fluency tasks.
      Studies suggest that these paradigms access semantic memory and executive
      function and are sensitive to frontal lobe disturbances. There are few studies in
      Brazilian samples on these paradigms. Objective: The present study investigated
      performance, and the effects of age, on verbal fluency tasks in Brazilian
      children. The results were compared with those of other studies, and the
      consistency of the scoring criteria data is presented. Methods: A sample of 119
      children (7 to 10 years old) was submitted to the three phonemic fluency (F, A,
      M) tasks and three semantic fluency (animals, clothes, fruits) tasks. The results
      of thirty subjects were scored by two independent examiners. Results: A
      significant positive correlation was found between the scores calculated by the
      two independent examiners. Significant positive correlations were found between
      performance on the semantic fluency task and the phonemic fluency task. The
      effect of age was significant for both tasks, and a significant difference was
      found between the 7- and 9-year-old subjects and between the 7- and 10-year-old
      subjects. The 8-year-old group did not differ to any of the other age groups.
      Conclusion: The pattern of results was similar to that observed in previous
      Brazilian and international studies.

PMID- 29213728
TI  - Depressive symptoms in elderly participants of an open university for elderly.
AB  - : Although the prevalence of depressive disorders among the elderly is lower than
      among the younger population, the presence of significant symptoms of depression
      is common in this group. Studies report that participation in social, educational
      and leisure activities is related to fewer depressive symptoms in this
      population. Objective: The aim of this study was to examine the prevalence of
      depression among elderly participants of an Open University for the Third Age, in
      terms of the time studying. Methods: The study had a cross-sectional design and
      the participation of 95.2% (n=184) of total enrollers in the first half of 2010
      on the activities of the Third Age Open University's School of Arts, Sciences and
      Humanities of the University of Sao Paulo. All participants answered a socio
      demographic questionnaire and the Geriatric Depression Scale (GDS-15). Results:
      An association between studying time of over one semester at the University of
      the Third Age and a lower rate of depressive symptoms, was observed. Conclusion:
      Study time of over one semester was associated with less depressive symptoms,
      acting as a possible protective factor against depression.

PMID- 29213729
TI  - Use of memory strategies among younger and older adults: Results from objective
      and subjective measures.
AB  - : Memory plays a fundamental role in the identity of people and in human life, as
      it enables us to interpret our surroundings and make decisions. It is known that
      the aging process can be accompanied by cognitive decline in some memory sub
      systems. However, the use of memory strategies can help encoding and retrieval of
      new information. Objective: The aim of this study was to identify and compare,
      using objective and subjective measures, which recall strategies are used
      spontaneously by young and older adults. Methods: Twenty-six first-year college
      students, and thirty-three seniors enrolled at the Third Age University of the
      same campus, completed a visual memory test including 18 black and white
      pictures, memorized a short story, and completed an open question about memory
      strategies, a memory check list to indicate strategies used, and a memory self
      efficacy scale. The Bousfield categorization measure was also calculated from the
      recall protocol. Results: Young adults demonstrated better performance than the
      older adults on the memory tasks, and were also more confident. Both groups
      reported using similar strategies. Conclusion: Young and older adults seem to
      tackle memory tasks in similar ways but young adults outperform seniors.

PMID- 29213730
TI  - Cognitive performance of long-term institutionalized elderly patients with
      schizophrenia: A case control study.
AB  - : Cognitive impairment is inherent to the ageing process. Several studies suggest
      that patients with late-life schizophrenia have more marked cognitive impairment.
      Objective: The aim of this study was to compare the cognitive performance of
      elderly institutionalized patients with schizophrenia and institutionalized
      elderly control patients without neurological or psychiatric diseases, matched
      for age, educational level and institutionalization time. Methods: The Cambridge
      Examination for Mental Disorders of the Elderly (CAMCOG) was used to test 10
      institutionalized elderly patients with schizophrenia. Results were compared with
      those of 10 institutionalized control patients with history of Hansen's disease.
      Results: Patients with schizophrenia showed a worse performance in terms of total
      CAMCOG score and on its subtests of orientation, language, abstraction, and
      memory (p<=0.05). Patients with schizophrenia also disclosed a non-significant
      trend toward lower scores on the MMSE and on calculus. Conclusion: Findings
      demonstrated that schizophrenia was associated to worse cognitive impairment in
      long-term institutionalized elderly patients compared with institutionalized
      patients without neurological or psychiatric diseases.

PMID- 29213731
TI  - Verbal fluency: Effect of time on item generation.
AB  - : The distribution of item generation/time in the performance of elderly on
      verbal fluency (VF) remains unknown. Objective: To analyze the number of items,
      their distribution and impact of the first quartile on the final test result.
      Methods: 31 individuals performed the tests (average age=74 years; schooling=8.16
      years). Results: The number of items produced in the first quartile differed from
      the other quartiles for both semantic and phonologic VF where 40% of items were
      produced in the first quartile. No effect of age was found and schooling
      influenced performance on the first and second quartiles of semantic VF and on
      the 1st, 2nd and 3rd quartiles of phonemic VF. Discussion: This study contributes
      with the finding that asymptotic levels are attained prior to the 30 seconds
      observed in other studies, being reached at the 15-second mark. Furthermore,
      schooling was found to be associated to the number of items produced in both the
      first and 2nd quartiles for semantic VF, and in 1st, 2nd and 3rd quartiles for
      phonemic fluency. Conclusion: The schooling effect was noted both in semantic and
      executive aspects of VF. The brief form of the VF test may represent a promising
      tool for clinical evaluation.

PMID- 29213732
TI  - Worries about memory loss and knowledge on Alzheimer's disease in community
      dwelling elderly from Brazil.
AB  - : Alzheimer's disease (AD) is the most common cause of dementia in the elderly.
      Efforts to determine risk factors for the development of AD are important for
      risk stratification and early diagnosis. Furthermore, there are no standardized
      practices for memory screening. Lack of knowledge on AD, perception of memory
      loss as part of normal aging, and poor socioeconomic conditions may also be
      implicated in the current situation of dementia. Objective: To evaluate knowledge
      of AD in a literate population of elders and correlate these findings with
      sociodemographic characteristics. Methods: A descriptive survey design study
      enrolled 994 volunteers from September 2007 to May 2008 in the city of Santos,
      Sao Paulo, Brazil, to answer a brief questionnaire consisting of 8 simple
      questions about knowledge of AD and worries about memory loss. Results: Greater
      knowledge about AD was associated with eight or more years of education, female
      gender and age between 60 and 70 years. Also, 52.8% of responders (95% CI - 49.5
      56.0%) answered that memory loss is part of normal aging and 77.5% (95% CI - 74.7
      80.1%) had never sought a doctor to evaluate their memories. Conclusion: Our
      study results reinforced that the first line of preventing late diagnosis of
      dementia is to act in health promotion, especially by targeting subjects older
      than 70 years of male gender and with lower educational level. It also provided
      evidence that strategies to promote physician initiative in treating memory
      problems are also paramount.

PMID- 29213733
TI  - Elderly patients with Alzheimer's disease and their family relationships:
      Caregiver perspectives.
AB  - Objective: The present study was to investigate the status of the family
      relationships of elderly patients with Alzheimer's disease from a caregiver's
      perspective. Methods: A total of sixteen relatives/caregivers of AD patients were
      assessed by applying a semi-structured questionnaire about family relationships.
      Frequency tables containing categorical variables (gender, schooling, personal
      income and current occupation) were compiled. Descriptive statistics were
      calculated of continuous variables such as age. Answers to open questions were
      submitted to Bardin's content analysis. The data were held on the Epidata program
      and statistical analysis was performed using the SPSS v.17.0 software package.
      Results: In line with the literature, the family was the main source of
      caregivers and the typical caregiver profile was female. In contrast to other
      studies, emotional burnout was not a major complaint in the sample studied. The
      ties created among family members and the life experience of each individual
      influences how interviewees cope with AD. Conclusion: The family relationships of
      caregivers of AD patients represent a constant challenge, due to changes in roles
      within the family structure as well as to disease progression. However,
      participation in psychological and socio-educational activities run by pioneering
      institutions in Brazil, act as a mediator of stress in the lives of both
      caregivers and patients.

PMID- 29213734
TI  - Deaf individuals who work with computers present a high level of visual
      attention.
AB  - : Some studies in the literature indicate that deaf individuals seem to develop a
      higher level of attention and concentration during the process of constructing of
      different ways of communicating. Objective: The aim of this study was to evaluate
      the level of attention in individuals deaf from birth that worked with computers.
      Methods: A total of 161 individuals in the 18-25 age group were assessed. Of
      these, 40 were congenitally deaf individuals that worked with computers, 42 were
      deaf individuals that did not work, did not know how to use nor used computers
      (Control 1), 39 individuals with normal hearing that did not work, did not know
      how to use computers nor used them (Control 2), and 40 individuals with normal
      hearing that worked with computers (Control 3). Results: The group of subjects
      deaf from birth that worked with computers (IDWC) presented a higher level of
      focused attention, sustained attention, mental manipulation capacity and
      resistance to interference compared to the control groups. Conclusion: This study
      highlights the relevance sensory to cognitive processing.

PMID- 29213735
TI  - Memory span measured by the spatial span tests of the Cambridge
      Neuropsychological Test Automated Battery in a group of Brazilian children and
      adolescents.
AB  - : The neuropsychological tests of spatial span are designed to measure attention
      and working memory. The version of the spatial span test in the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) evaluates these functions
      through the recall of sequences of spatial locations presented to the subject.
      Objective: The present study investigated how age, gender and educational level
      might affect the performance of the non-verbal system. Methods: A total of 60
      children and adolescents aged 6 to 18 years were assessed (25 males and 35
      females). Results: The results showed no gender differences in test performance.
      Children with six or more years of education showed better performance than
      children with less than three years of education. Older children had more
      schooling and thus were able to recall a greater number of items. Span length
      values proved similar to a previous large normative study which also employed the
      CANTAB Spatial Span (De Luca et al., 2003). Conclusion: The similarity in
      performance of the Brazilian children and adolescents studied and the group of
      Australian participants examined by the cited authors, despite the socio-cultural
      and economical differences, points to the suitability of the task for the
      assessment of attention and working memory in Brazilian children.

PMID- 29213737
TI  - Brief reviews.

PMID- 29213736
TI  - Clinicopathologic analysis of progressive non-fluent aphasia and corticobasal
      degeneration: Case report and review.
AB  - Objective: To investigate progressive non-fluent aphasia and histopathologically
      proven corticobasal degeneration. Methods: We evaluated symptoms, signs,
      neuropsychological deficits, and radiology data longitudinally, in a patient with
      autopsy-proven corticobasal degeneration and correlated these observations
      directly to the neuroanatomic distribution of the disease. Results: At
      presentation, a specific pattern of cognitive impairment was evident with an
      extreme extrapyramidal motor abnormality. Follow-up examination revealed
      persistent impairment of praxis and executive functioning, progressive worsening
      of language performance, and moderately preserved memory. The motor disorder
      manifested and worsened as the condition progressed. Many of the residual nerve
      cells were ballooned and achromatic with eccentric nuclei. Tau-immunoreactive
      pathology was significantly more prominent in neurons in the frontal and parietal
      cortices and dentate nuclei than in temporal neocortex, hippocampi and brainstem.
      Conclusion: The clinical diagnosis of progressive non-fluent aphasia secondary to
      corticobasal degeneration hinged on a specific pattern of impaired cognition as
      well as an extrapyramidal motor disorder, reflecting the neuroanatomic
      distribution of the disease in frontal and anterior temporal cortices and the
      dentate nuclei.

PMID- 29213738
TI  - In the September 2011 issue.

PMID- 29213739
TI  - Criteria for the diagnosis of Alzheimer's disease: Recommendations of the
      Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy
      of Neurology.
AB  - This consensus prepared by the Scientific Department of Cognitive Neurology and
      Aging of the Brazilian Academy of Neurology is aimed at recommending new criteria
      for the diagnosis of dementia and Alzheimer's disease (AD) in Brazil. A revision
      was performed of the proposals of clinical and of research criteria suggested by
      other institutions and international consensuses. The new proposal for the
      diagnosis of dementia does not necessarily require memory impairment if the
      cognitive or behavioral compromise affects at least two of the following domains:
      memory, executive function, speech, visual-spatial ability and change in
      personality. For the purpose of diagnosis, AD is divided into three phases:
      dementia, mild cognitive impairment and pre-clinical phase, where the latter only
      applies to clinical research. In the dementia picture, other initial forms were
      accepted which do not involve amnesia and require a neuroimaging examination.
      Cerebrospinal fluid biomarkers are recommended for study, but can be utilized as
      optional instruments, when deemed appropriate by the clinician.

PMID- 29213740
TI  - Cognitive, functional and behavioral assessment: Alzheimer's disease.
AB  - A review of the evidence on cognitive, functional and behavioral assessment for
      the diagnosis of dementia due to Alzheimer's disease (AD) is presented with
      revision and broadening of the recommendations on the use of tests and batteries
      in Brazil for the diagnosis of dementia due to AD. A systematic review of the
      literature (MEDLINE, LILACS and SCIELO database) was carried out by a panel of
      experts. Studies on the validation and/or adaptation of tests, scales and
      batteries for the Brazilian population were analyzed and classified according to
      level of evidence. There were sufficient data to recommend the IQCODE, DAFS-R,
      DAD, ADL-Q and Bayer scale for the evaluation of instrumental activities of daily
      living, and the Katz scale for the assessment of basic activities of daily
      living. For the evaluation of neuropsychiatric symptoms, the Neuropsychiatric
      Inventory (NPI) and the CAMDEX were found to be useful, as was the Cornell scale
      for depression in dementia. The Mini-Mental State Examination has clinical
      utility as a screening test, as do the multifunctional batteries (CAMCOG-R, ADAS
      COG, CERAD and MDRS) for brief evaluations of several cognitive domains. There
      was sufficient evidence to recommend the CDR scale for clinical and severity
      assessment of dementia. Tests for Brazilian Portuguese are recommended by
      cognitive domain based on available data.

PMID- 29213741
TI  - Diagnosis of Alzheimer's disease in Brazil: Supplementary exams.
AB  - This article presents a review of the recommendations on supplementary exams
      employed for the clinical diagnosis of Alzheimer's disease (AD) in Brazil
      published in 2005. A systematic assessment of the consensus reached in other
      countries, and of articles on AD diagnosis in Brazil available on the PUBMED and
      LILACS medical databases, was carried out. Recommended laboratory exams included
      complete blood count, serum creatinine, thyroid stimulating hormone (TSH),
      albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions
      for syphilis and serology for HIV in patients aged younger than 60 years with
      atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed
      tomography or - preferably - magnetic resonance exams, are indicated for
      diagnostic investigation of dementia syndrome to rule out secondary etiologies.
      Functional neuroimaging exams (SPECT and PET), when available, increase
      diagnostic reliability and assist in the differential diagnosis of other types of
      dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset
      dementia with atypical clinical presentation or course, for communicant
      hydrocephaly, and suspected inflammatory, infectious or prion disease of the
      central nervous system. Routine electroencephalograms aid the differential
      diagnosis of dementia syndrome with other conditions which impair cognitive
      functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms
      is not recommended for diagnostic purposes or for assessing the risk of
      developing the disease. Biomarkers related to the molecular alterations in AD are
      largely limited to use exclusively in research protocols, but when available can
      contribute to improving the accuracy of diagnosis of the disease.

PMID- 29213742
TI  - Treatment of Alzheimer's disease in Brazil: I. Cognitive disorders.
AB  - This article reports the recommendations of the Scientific Department of
      Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the
      treatment of Alzheimer's disease (AD) in Brazil, with special focus on cognitive
      disorders. It constitutes a revision and broadening of the 2005 guidelines based
      on a consensus involving researchers (physicians and non-physicians) in the
      field. The authors carried out a search of articles published since 2005 on the
      MEDLINE, LILACS and Cochrane Library databases. The search criteria were
      pharmacological and non-pharmacological treatment of cognitive disorders in AD.
      Studies retrieved were categorized into four classes, and evidence into four
      levels, based on the 2008 recommendations of the American Academy of Neurology.
      The recommendations on therapy are pertinent to the dementia phase of AD.
      Recommendations are proposed for the treatment of cognitive disorders
      encompassing both pharmacological (including acetyl-cholinesterase inhibitors,
      memantine and other drugs and substances) and non-pharmacological (including
      cognitive rehabilitation, physical activity, occupational therapy, and music
      therapy) approaches. Recommendations for the treatment of behavioral and
      psychological symptoms of dementia due to Alzheimer's disease are included in a
      separate article of this edition.

PMID- 29213743
TI  - Treatment of Alzheimer's disease in Brazil: II. Behavioral and psychological
      symptoms of dementia.
AB  - This article reports the recommendations of the Scientific Department of
      Cognitive Neurology and Aging of the Brazilian Academy of Neurology for the
      treatment of Alzheimer's disease (AD) in Brazil, with special focus on behavioral
      and psychological symptoms of dementia (BPSD). It constitutes a revision and
      broadening of the 2005 guidelines based on a consensus involving researchers
      (physicians and non-physicians) in the field. The authors carried out a search of
      articles published since 2005 on the MEDLINE, LILACS and Cochrane Library
      databases. The search criteria were pharmacological and non-pharmacological
      treatment of the behavioral and psychological symptoms of AD. Studies retrieved
      were categorized into four classes, and evidence into four levels, based on the
      2008 recommendations of the American Academy of Neurology. The recommendations on
      therapy are pertinent to the dementia phase of AD. Recommendations are proposed
      for the treatment of BPSD encompassing both pharmacological (including acetyl
      cholinesterase inhibitors, memantine, neuroleptics, anti-depressives,
      benzodiazepines, anti-convulsants plus other drugs and substances) and non
      pharmacological (including education-based interventions, physiotherapy,
      occupational therapy, music therapy, therapy using light, massage and art
      therapy) approaches. Recommendations for the treatment of cognitive disorders of
      AD symptoms are included in a separate article of this edition.

PMID- 29213744
TI  - Effects of motor and cognitive dual-task performance in depressive elderly,
      healthy older adults, and healthy young individuals.
AB  - : Impairments in dual-task performance can be observed in healthy older adults
      when motor and cognitive assignments are applied simultaneously. According to the
      hypofrontality hypothesis, there may be a reduction in frontal cognitive function
      during exercise. Objective: The aim of the present study was to compare the
      performance changes on cognitive tests of depressive elderly (n=10), healthy
      older adults (n=10), and healthy young individuals (n=10) during cycle ergometer
      exercise. Methods: The groups were submitted to a working memory test, a short
      memory test and a semantic memory test, before and during a 20-minute cycle
      ergometer exercise at 80% of their age-predicted maximal heart rate. Results:
      Significant differences (p=0.04) were observed in scores on the digit backward
      test during exercise when young individuals were compared to healthy older
      adults. This result indicates that young subjects, as expected, had better
      performance than elderly. No significant differences were found among the groups
      for the digit forward subtest (p=0.40) or the vocabulary test (p=0.69).
      Conclusion: Data from this study showed that healthy older adults had impaired
      performance on higher cognitive tasks when these assignments were applied
      together with motor tasks.

PMID- 29213745
TI  - Neuropsychiatric symptoms as the main determinant of caregiver burden in
      Alzheimer's disease.
AB  - : Caregiver burden is common in Alzheimer's disease (AD), decreasing the quality
      of life among caregivers and patients. Projections of aging and aging-related
      diseases such as AD in developing countries justify additional data about this
      issue because people living in these countries have shown similarly high levels
      of caregiver strain as in the developed world. Objective: The aim of this study
      was to analyze the association of AD caregivers' burden with patients'
      neuropsychiatric symptoms (NPS), cognitive status, severity of dementia,
      functional capacity, caregiver sociodemographic characteristics, and the
      characteristics of care provided by caregivers. Methods: A cross-sectional study
      was conducted in a sample of 39 consecutive AD patients and their primary
      caregivers. NPS were evaluated using the Neuropsychiatric Inventory (NPI).
      Severity of dementia was assessed with the Clinical Dementia Rating (CDR) scale.
      Functional capacity was assessed using the Katz and Lawton scales. The burden
      level was rated using the Burden Interview (BI). Sociodemographic characteristics
      of caregivers and the characteristics of care provided by them were evaluated.
      The Mann-Whitney U-test, Kruskal-Wallis test and Spearman's rho coefficient were
      performed. Results: The BI had a moderate correlation with NPI intensity
      (rho=0.563), p<001. Female caregivers reported a greater level of burden
      (p=0.031) than male caregivers. The other variables were not significantly
      associated to caregiver burden. Conclusion: NPS were the main determinant of
      burden in primary caregivers of AD patients. This result underscores the need for
      prevention and treatment of these symptoms. Sex also had an effect on caregiver
      burden, but the small male sample in this study precludes the generalization of
      this finding.

PMID- 29213746
TI  - Brazilian air traffic controllers exhibit excessive sleepiness.
AB  - : Excessive sleepiness (ES) is an increased tendency to initiate involuntary
      sleep for naps at inappropriate times. Objective: The objective of this study was
      to assess ES in air traffic controllers (ATCo). Methods: 45 flight protection
      professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten
      or more years in the profession (ATCo>=10, n=15) and ATCo with less than ten
      years in the profession (ATCo<10, n=15) and 15 aeronautical information services
      operators (AIS), subdivided into AIS with ten years or more in the profession
      (AIS>=10, n=8) and AIS with less than ten years in the profession (AIS<10, n=7),
      who were included as the control group. The Epworth Sleepiness Scale and
      Maintenance of Wakefulness Test were used for evaluating subjective and objective
      excessive sleepiness. Kruskal-Wallis was used for ES and Mann-Whitney for sleep
      latency (SL), collection time in minutes (mins), and expressed as Median (Minimum
      Maximum), p<0.05. Results: ATCo>=10 12 (6-14) mins and ATCo<10 10 (1-15) mins
      showed greater sleepiness compared to CONTROL1 7 (3-8) mins and CONTROL2 6 (4-6)
      mins, p=0.001*. A total of 77.27% of the ATCo and 16.67% of the AIS had an SL of
      less than 20 minutes. The ATCo presented an SL of 16.59 (3.25-40), lower than
      that of the AIS of 31.71 (10.63-40) mins, p<0.05*. Conclusion: Brazilian air
      traffic controllers exhibit excessive sleepiness.

PMID- 29213747
TI  - Subjective and psychological well-being of students of a University of the Third
      Age: Benefits of continuing education for psychological adjustment in the
      elderly.
AB  - Objectives: The present study sought to characterize the degree of general
      satisfaction with life and degree of satisfaction on four domains: health,
      physical capacity, mental capacity and social involvement, and to determine the
      characteristics of self-reports of individuals enrolled on the program in
      relation to their psychological well-being focusing on the dimensions: autonomy,
      personal growth, control, positive relationships with others, purpose, personal
      acceptance and generativity, and to analyse the effect of time studying on level
      of well-being. Method: A total of 140 elderly students of a University for the
      Third Age took part in the study. The Global Satisfaction With Life Scale and the
      Self Development Scale (with six psychological well-being subscales) were
      applied. Continuous variables for the two groups were compared using the Mann
      Whitney test. Spearman's correlation coefficient was used to analyze the
      relationship among numeric variables. Internal consistency of the instrument
      scales was analysed by calculating Cronbach's alpha coefficient. Results: Results
      showed that students who had attended the University of the Third Age for six
      months or longer had a higher level of satisfaction with life and greater
      psychological adjustment compared with new entrants to the same institution.
      Conclusion: The study results confirmed the positive effects of continuing
      education on the well-being of elderly and its contribution to successful aging.

PMID- 29213749
TI  - Brief reviews.

PMID- 29213748
TI  - Effects of a psychoeducational intervention in family caregivers of people with
      Alzheimer's disease.
AB  - : Psychoeducational activities are a way of promoting help for caregivers of
      patients with Alzheimer's disease, representing a forum for knowledge sharing,
      and in which the primary focus is on psychological themes aimed at carers
      developing coping skills and strategies. Objective: The main objective of this
      study was to gauge perceptions about care and its impact among family caregivers
      of patients with AD participating in a psychoeducational group intervention, as
      well as the possible positive and negative aspects associated with this role. The
      subjective impact of AD on the lives of these caregivers was assessed on each of
      the dimensions of the Caregiver Burden Scale using a semi-directed interview on
      perceptions about care. Methods: This was a prospective study, in which
      information was collected twice, before and after, psychoeducational
      intervention. Through the application of the scale, benefits were evident for all
      dimensions assessed in the instrument (general strain, isolation, disappointment,
      emotional involvement and environment). Results: The results showed that after
      the psychoeducational intervention, caregivers felt less burdened by care
      compared to pre-intervention. Conclusion: These findings confirm that expanded
      implementation of psychoeducational interventions for caregivers of patients with
      AD can be beneficial for both caregivers and patients.

PMID- 29213750
TI  - In the December 2011 issue.

PMID- 29213751
TI  - The possibility of physicalism.
AB  - Modern science has undermined belief in countless imaginary causalities. What is
      the nature of the relation between mind and brain? Philosophers have debated the
      issue for millennia, but it is only in the last twenty years that empirical
      evidence has begun to uncover some of the secrets of this ancient riddle. This
      lecture explores the possiblity that advances in neuroscience will undermine and
      subvert our intuitive, mentalist understanding of the mind-body relationship.
      Recent findings in neuroscience seem to support the notions that (i) mental
      events are a subclass of neurophysiological events, and (ii) they are devoid of
      causal efficacy upon the workings of the brain. If physicalism is true then the
      belief in the causal potency of conscious thoughts and free will are bound to
      join company with countless other imaginary causalities exploded by the progress
      of science.

PMID- 29213752
TI  - Vascular dementia: Diagnostic criteria and supplementary exams. Recommendations
      of the Scientific Department of Cognitive Neurology and Aging of the Brazilian
      Academy of Neurology. Part I.
AB  - Vascular dementia (VaD) is the most prevalent form of secondary dementia and the
      second most common of all dementias. The present paper aims to define guidelines
      on the basic principles for treating patients with suspected VaD (and vascular
      cognitive impairment - no dementia) using an evidence-based, systematized
      approach. The knowledge used to define these guidelines was retrieved from
      searches of several databases (Medline, Scielo, Lilacs) containing scientific
      articles, systematic reviews, meta-analyses, largely published within the last 15
      years or earlier when pertinent. Information retrieved and selected for relevance
      was used to analyze diagnostic criteria and to propose a diagnostic system
      encompassing diagnostic criteria, anamnesis, as well as supplementary and
      clinical exams (neuroimaging and laboratory). Wherever possible, instruments were
      selected that had versions previously adapted and validated for use in Brazil
      that take into account both schooling and age. This task led to proposed
      protocols for supplementary exams based on degree of priority, for application in
      clinical practice and research settings.

PMID- 29213753
TI  - Vascular dementia: Cognitive, functional and behavioral assessment.
      Recommendations of the Scientific Department of Cognitive Neurology and Aging of
      the Brazilian Academy of Neurology. Part II.
AB  - Vascular dementia (VaD) is the most prevalent form of secondary dementia and the
      second most common of all dementias. The present paper aims to define guidelines
      on the basic principles for treating patients with suspected VaD (and vascular
      cognitive impairment - no dementia) using an evidence-based approach. The
      material was retrieved and selected from searches of databases (Medline, Scielo,
      Lilacs), preferentially from the last 15 years, to propose a systematic way to
      assess cognition, function and behavior, and disease severity staging, with
      instruments adapted for our milieu, and diagnosis disclosure. The present
      proposal contributes to the definition of standard diagnostic criteria for VaD
      based on various levels of evidence. It is noteworthy that only around half of
      the population of patients with vascular cognitive impairment present with
      dementia, which calls for future proposals defining diagnostic criteria and
      procedures for this condition.

PMID- 29213754
TI  - Treatment of vascular dementia. Recommendations of the Scientific Department of
      Cognitive Neurology and Aging of the Brazilian Academy of Neurology.
AB  - Scientific Department of Cognitive Neurology and Aging of ABN had a consensus
      meeting to write recommendations on treatment of vascular dementia, there was no
      previous issue. This disease has numerous particularities and can be considered a
      preventable dementia. Prevention treatment is primary care of vascular risk
      factors or a secondary prevention of factors that could cause recurrence of
      ischemic or hemorrhagic brain modifications. In these guidelines we suggested
      only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed
      current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases.
      Recommendations are concern to the following factors and their prevention
      evidences, association, or treatment of vascular dementia: physical activity,
      tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus,
      obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep
      apnea, carotid revascularization, symptomatic pharmacological treatment.

PMID- 29213755
TI  - Differential diagnosis between dementia and psychiatric disorders: Diagnostic
      criteria and supplementary exams. Recommendations of the Scientific Department of
      Cognitive Neurology and Aging of the Brazilian Academy of Neurology.
AB  - In 2005, the Scientific Department of Cognitive Neurology and Aging of the
      Brazilian Academy of Neurology published recommendations for the diagnosis of
      Alzheimer's disease These recommendations were updated following a review of
      evidence retrieved from national and international studies held on PUBMED, SCIELO
      and LILACS medical databases. The main aims of this review article are as
      follows: 1) to present the evidence found on Brazilian (LILACS, SCIELO) and
      International (MEDLINE) databases from articles published up to May 2011, on the
      differential diagnosis of these psychiatric disorders and dementia, with special
      focus on Dementia due to Alzheimer's and vascular dementia, including a review of
      supplementary exams which may facilitate the diagnostic process; and2) to propose
      recommendations for use by clinicians and researchers involved in diagnosing
      patients with dementia. Differential diagnosis between dementia and other
      neuropsychiatric disorders should always include assessments for depression,
      delirium, and use of psychoactive substances, as well as investigate the use of
      benzodiazepines, anti-epileptics and pattern of alcohol consumption.

PMID- 29213756
TI  - Judgment in Mild Cognitive Impairment and Alzheimer's disease.
AB  - Judgment is the capacity to make decisions after considering available
      information, contextual factors, possible solutions and probable outcomes. Our
      aim was to investigate previous research studies regarding assessment of judgment
      in older adults with different degrees of cognitive impairment. To this end, a
      search of Pubmed and Lilacs electronic databases for studies published from
      January 1990 until August 2011 in English, Spanish and Portuguese was carried
      out. The terms used were "judgment" combined with the terms "dementia" or "Mild
      Cognitive Impairment" (MCI) or "Alzheimer's disease" (AD). Some studies showed
      that MCI and AD patients had impaired judgment. There is a lack of specific
      methods to measure judgment capacity, and data on judgment abilities in older
      adults with MCI and dementia are scarce. No studies with specific measures of
      judgment capacity in other dementias were found.

PMID- 29213757
TI  - Cognitive impairment in multiple system atrophy: Changing concepts.
AB  - Multiple system atrophy (MSA) is characterized by a variable combination of
      cerebellar ataxia, parkinsonism and pyramidal signs associated with autonomic
      failure. Classically, cognitive impairment was not considered a clinical feature
      of MSA and dementia was pointed out as an exclusion diagnostic criteria. Based on
      comprehensive neuropsychological assessment, cognitive impairment was found to be
      a frequent feature in MSA, and clinically-defined dementia is now reported in 14
      16% of cases. This article reviews the current data on cognitive impairment in
      MSA along with its neuropsychological profile and pathophysiology.

PMID- 29213759
TI  - Cross-cultural Adaptation of the "Functional Activities Questionnaire - FAQ" for
      use in Brazil.
AB  - Objective: The aim of this paper was to present the results of the first stage of
      cross-cultural adaptation of the Functional Activities Questionnaire (FAQ).
      Methods: The tool was subjected to translation and re-translation, and the test
      retest reliability of a proposed version for use in Brazil was analyzed. Results:
      Of the 548 questionnaire respondents, a convenience sample of 68 informants was
      selected for retesting. Internal consistency was measured by Cronbach's alpha
      (0.95) while test-retest reliability was assessed using intra-class correlation
      (0.97). The findings have shown that FAQ is brief - averaging seven minutes to
      apply, easily understood and has good intra-rater test-retest reliability.
      Conclusion: Our results suggest this adapted version of the FAQ is a reliable and
      stable tool which may be useful for assessing function in Brazilian elderly.
      Notwithstanding, the version should be subjected to further analysis with the aim
      of reaching functional equivalence.

PMID- 29213758
TI  - A systematic review of the neurobiological aspects of memory in the aging
      process.
AB  - : A systematic review of the neuroanatomical literature was performed to
      determine the neuropharmacological aspects most relevant to the study of memory
      processes. Articles were retrieved using the search terms "biology of memory",
      "memory and aging", "memory impairment", "elderly and memory," and their
      equivalents in Portuguese. Of the studies surveyed, five studies dealt with
      epidemiological and demographic issues, 12 were clinical trials i.e. were based
      on testing and implementation of instruments in human subjects, 33 studies were
      basic research involving studies of mice, rats and non-human primates, and
      biochemical and in vitro trials and finally, 52 studies were literature reviews
      or book chapters which in our view, fell into this category. Conclusions: The
      work sought to highlight which neural networks are most involved in processing
      information, as well as their location within brain regions and the way in which
      neurotransmitters interact with each other for the formation of these memories.
      Moreover, it was shown how memory changes during the normal human aging process,
      both positively and negatively, by analyzing the morphological alterations that
      occur in the brain of aging individuals.

PMID- 29213760
TI  - Factors influencing possible delay in the diagnosis of Alzheimer's disease:
      Findings from a tertiary Public University Hospital.
AB  - : Alzheimer's disease (AD) is characterized by impairment in memory and autonomy,
      causing excessive pressure on family and an overburdened health care system.
      Early diagnosis, with the appropriate treatment, is important to reduce the
      pattern of disease progression. Objective: The study sought to identify the most
      probable causes of delay in diagnosis. Methods: A cross-sectional study involving
      AD patients followed at an Outpatient Geriatric Clinic from a tertiary public
      university hospital was conducted between June 2009 and February 2011. Results:
      Ninety-four patients were evaluated (66% women), aged 77.76+/-6.8 years and with
      median educational level of 3 years (95% CI 2.7-3.80). Regarding severity of
      dementia, 51.8% of patients were classified as having mild dementia (CDR 1), 40%
      moderate dementia (CDR 2) and 8.2% severe dementia (CDR 3). Mean educational
      level of caregivers was 8.3+/-3.9 years. Among those who believed there was a
      delay, 36% stated that the "family thought that the changes were normal for the
      age of the patient" reporting average delay of 1.8 years (95% CI: 1.3-2.5) while
      45.3% stated that the "doctor did not reach a diagnosis" reporting a median delay
      of 1.5 years (95% CI: 1.4-2.3). Conclusion: Based on these results, it can be
      concluded the time between onset of symptoms and diagnosis was excessive. This
      study may be useful to help increase awareness of issues not sufficiently
      discussed in the literature, such as diagnostic delay and influence of
      caregivers' educational level on treatment.

PMID- 29213761
TI  - Influence of Rivastigmine transdermal on butyrylcholinesterase levels in patients
      with Alzheimer's disease.
AB  - : Cholinesterase inhibitors (ChE-Is) are among the main drugs approved for the
      treatment of Alzheimer's disease (AD). Rivastigmine in the form of a transdermal
      patch is an alternative delivery method, and can give greater treatment
      compliance. Objectives: To conduct a preliminary assessment of the neurocognitive
      and biological effects of oral and transdermal Rivastigmine in patients with AD
      and to identify a potential biological marker and demonstrate a possible
      relationship between esterase levels and behavioral scores of AD patients.
      Methods: Forty patients with AD were treated with cholinesterase inhibitors (ChE
      Is), evaluated using the MMSE and NPI, and simultaneously sampled to determine
      their serum levels of AChE and BuChE for 180 days. Results: The differences
      obtained between oral and transdermal forms, as assessed by the MMSE and NPI
      scores of the AD patients, were not significant at the three time points examined
      (0, 90, and 180 days). However, serum BuChE levels of the transdermal group
      differed significantly (p<0.0004) compared with those of the oral group at 90
      days. Conclusion: Use of a transdermal ChE-I, rivastigmine tartrate significantly
      reduced BuChE levels in the AD patients studied.

PMID- 29213763
TI  - Brief reviews.

PMID- 29213762
TI  - Pragmatic and executive functions in traumatic brain injury and right brain
      damage: An exploratory comparative study.
AB  - Objective: To describe the frequency of pragmatic and executive deficits in right
      brain damaged (RBD) and in traumatic brain injury (TBI) patients, and to verify
      possible dissociations between pragmatic and executive functions in these two
      groups. Methods: The sample comprised 7 cases of TBI and 7 cases of RBD. All
      participants were assessed by means of tasks from the Montreal Communication
      Evaluation Battery and executive functions tests including the Trail Making Test,
      Hayling Test, Wisconsin Card Sorting Test, semantic and phonemic verbal fluency
      tasks, and working memory tasks from the Brazilian Brief Neuropsychological
      Assessment Battery NEUPSILIN. Z-score was calculated and a descriptive analysis
      of frequency of deficits (Z< -1.5) was carried out. Results: RBD patients
      presented with deficits predominantly on conversational and narrative discursive
      tasks, while TBI patients showed a wider spread pattern of pragmatic deficits.
      Regarding EF, RBD deficits included predominantly working memory and verbal
      initiation impairment. On the other hand, TBI individuals again exhibited a
      general profile of executive dysfunction, affecting mainly working memory,
      initiation, inhibition, planning and switching. Pragmatic and executive deficits
      were generally associated upon comparisons of RBD patients and TBI cases, except
      for two simple dissociations: two post-TBI cases showed executive deficits in the
      absence of pragmatic deficits. Discussion: Pragmatic and executive deficits can
      be very frequent following TBI or vascular RBD. There seems to be an association
      between these abilities, indicating that although they can co-occur, a cause
      consequence relationship cannot be the only hypothesis.

PMID- 29213765
TI  - Editorial: In the March 2012 issue.

PMID- 29213767
TI  - Neural correlates of behavioural symptoms in behavioural variant frontotemporal
      dementia and Alzheimer's disease: Employment of a visual MRI rating scale.
AB  - : Frontotemporal dementia (FTD) patients often present with severe behavioural
      disturbances and concomitant lack of insight. The underlying neural correlates of
      these disturbances are mostly attributed to prefrontal cortex dysfunction, but
      are still poorly understood. Objectives: The current study explores whether a
      simple visual magnetic resonance imaging (MRI) rating scale in combination with
      the Frontal System Behaviour Scale (FrSBe) can be used to identify the prefrontal
      correlates of behavioural symptoms in behavioural variant frontotemporal dementia
      (bvFTD) and Alzheimer's disease (AD). Methods: Forty-eight patients with a
      clinical diagnosis of bvFTD and AD participated in the study. Their behavioural
      profiles were assessed using the Frontal System Behaviour Scale (FrSBe) and cross
      correlated to the atrophy of the sub-regions in the prefrontal cortex using a 5
      point visual rating scale of MRI scans. Results: Patients with bvFTD showed
      higher incidence of behavioural disturbances than AD with apathy being the most
      significant. BvFTD patients also showed the highest incidence of atrophy in the
      orbital frontal cortex and this atrophy was correlated with the apathetic
      features. Conclusions: Employment of a simple visual MRI rating scale can be used
      in combination with a behavioural screening test to identify reliably the
      behavioural symptoms in bvFTD and AD. These findings will inform the diagnostic
      accuracy of the neural correlates of behavioural dysfunction in bvFTD in the
      future.

PMID- 29213766
TI  - Cognitive assessment instruments in Parkinson's disease patients undergoing deep
      brain stimulation.
AB  - : Deep Brain Stimulation (DBS) is a widely used surgical technique in individuals
      with Parkinson's disease (PD) that can lead to significant reductions in motor
      symptoms. Objectives: To determine, from publications, the most commonly used
      instruments for cognitive evaluation of individuals with PD undergoing DBS.
      Methods: A systematic review of the databases: PubMed, Medline, EBECS, Scielo and
      LILACS was conducted, using the descriptors "Deep Brain Stimulation", "Verbal
      Fluency", "Parkinson Disease", "Executive Function", "Cognition" and "Cognitive
      Assessment" in combination. Results: The Verbal Fluency test was found to be the
      most used instrument for this investigation in the studies, followed by the
      Boston Naming Test. References to the Stroop Test, Trail Making Test, and Rey's
      Auditory Verbal Learning Test were also found. Conclusions: The validation of
      instruments for this population is needed as is the use of batteries offering
      greater specificity and sensitivity for the detection of cognitive impairment.

PMID- 29213768
TI  - A model for pediatric and neuropsychological screening assessment of children
      with learning disabilities.
AB  - Objectives: The high frequency of learning difficulties, attention disorders or
      developmental delay in children in the early years of schooling has resulted in a
      greater demand for pediatric services. Such services generally include
      assessments covering various specialties, are lengthy and often inaccessible to
      families due to prohibitively high cost. This paper presents an economically
      efficient model of interdisciplinary diagnosis. Methods: A group of 109 Brazilian
      students from public schools aged between 5 and 14 years old, referred by
      teachers for a history of learning disabilities, behavioral changes or language
      problems, was evaluated at the NANI (Nucleo de Atendimento Neuropsicologico
      Infantil). Assessments were performed simultaneously during a single day's
      attendance and comprised clinical-genetic examination, behavioral assessment and
      neuropsychological screening, specially developed for the process. The multiaxial
      system of DSM-IV was adopted for diagnostic description. Results: The results
      revealed heterogeneity in diagnoses which included specific learning disorders
      (25.7%), mild intellectual disabilities (17.43%), as well as suspected dysmorphic
      features (11.93%). Logistic regression showed good sensitivity of
      neuropsychological screening in the detection of predictive factors for specific
      developmental disorders, while working memory (p=0.05) and language (p=0.02)
      problems were found to be higher risk. Conclusions: The model adopted proved to
      be useful for defining the diagnosis of several conditions in infancy, and can be
      incorporated into specialized clinics such as psychiatric or developmental
      pediatric services.

PMID- 29213769
TI  - Executive functions and sustained attention: Comparison between age groups of 19
      39 and 40-59 years old.
AB  - : Few studies involving the cognition of middle-aged adults are available in the
      international literature, particularly investigating the process of cognitive
      aging, executive components and attention. Objectives: The aim of this study was
      to investigate whether there are differences in performance on neuropsychological
      tasks of executive functions and sustained attention between two age groups.
      Methods: The sample consisted of 87 adults aged from 19 to 59 years old, divided
      into two groups according to the age variable (younger adults and middle-aged
      adults). All participants were Brazilian and had no sensory, psychiatric or
      neurological disorders; subjects also had no history of alcohol abuse, and no
      self-reported use of illicit drugs or antipsychotics. The neuropsychological
      instruments administered were the Hayling Test, Trail Making Test, Bells Test and
      verbal fluency tasks. Results: Groups showed no significant differences in
      relation to sociodemographic variables, educational level or frequency of reading
      and writing habits. The younger adult group performed better than the middle-aged
      group on tasks that involved mainly processing speed, cognitive flexibility and
      lexical search. Conclusions: These findings serve as a valuable reference for
      cognitive processing in middle-aged adults, since a large number of comparative
      studies focus only on the younger and later phases of adulthood. Additional
      studies are needed to investigate possible interaction between different factors
      such as age and education.

PMID- 29213770
TI  - Training of executive functions in healthy elderly: Results of a pilot study.
AB  - : Executive functions (EF) refer to the cognitive skills necessary to formulate a
      goal, plan, execute plans effectively, and to perform self-monitoring and self
      correction. Several aspects of EF change during the normal aging process.
      Objectives: To train skills associated with executive functions in the elderly
      and to detect possible impact on objective EF tests and self-reports of
      functional status. Methods: A cross-sectional study involving an intervention and
      pre and post testing was carried out. Study participants included 26 seniors
      assigned to an experimental group (EG) and given six sessions of cognitive
      intervention, and 17 seniors assigned to a control group (CG) who completed pre
      and post testing only. All participants were enrolled in an Open University for
      the Third Age. The following tests were used to measure outcome: the Mini-Mental
      State Examination (MMSE), the Geriatric Depression Scale (GDS), the Story subtest
      of the Rivermead Behavioral Memory Test (RBMT) (versions A and B), semantic
      verbal fluency fruit category, and verbal fluency with phonological constraints
      (FAS), WAIS-III Digit Span, Clock Drawing Test (CDT), Trail Making Part A and the
      Pfeffer Functional Assessment Questionnaire (PFAQ). Delta scores were calculated
      (post-test score minus pretest score) to assess the impact of the intervention.
      Results: In the post test, the CG showed significant improvement on the RBMT
      Story recall and Digit Span but a decline in verbal fluency. The EG remained
      stable in terms of pre and post test scores. Conclusions: The intervention did
      not enhance performance on the EF tests. It is noteworthy that the EG received
      only a small number of sessions which may not have been sufficient to generate
      improvement. Alternatively, the lack of group differences observed could be
      associated to participation in other workshops offered at the university.

PMID- 29213771
TI  - Screening of cognitive impairment by general internists using two simple
      instruments.
AB  - : General internists (GIs) tend to overlook cognitive impairment in the elderly.
      Lack of time to diagnose and/or poor knowledge on how to use screening
      instruments may be the reasons for this shortcoming. Objectives: To verify the
      efficacy of simple instruments in the screening of cognitive impairment in
      elders. Methods: In a previous study, 248 patients aged >=65 that had been
      assisted by GIs within outpatient services of a public university hospital in Sao
      Paulo, Brazil, were evaluated. The Mini-Mental State Examination and/or the
      Informant Questionnaire on Cognitive Decline in the Elderly (short-IQCODE) were
      employed to classify patients into probable cognitively impaired cases or
      otherwise. Other tests and questionnaires were also applied, but were not used to
      perform this classification. After full assessment and consensus meetings, cases
      were classified into dementia, cognitively impaired not demented, and without
      cognitive impairment. In this study, the sensitivity and specificity of the
      combined use of the category fluency test (CFT) and the Functional Activities
      Questionnaire (FAQ) was evaluated as if used as screening instruments for the
      whole sample. Results: The combined use of the CFT and/or FAQ showed sensitivity
      of 88.3% and specificity of 76.5% in the screening of cognitive impairment for
      the whole sample. Conclusions: Two simple and easy-to-apply instruments showed
      high sensitivity and reasonable specificity, and are probably useful for the
      screening of cognitive impairment in the elderly in outpatient services.

PMID- 29213772
TI  - Early and severe cognitive impairment in multiple sclerosis.
AB  - Objectives: To report on four new cases of severe cognitive impairment in the
      early stages of multiple sclerosis (MS) and to review data on the subject since
      few cases have been reported worldwide. Methods: Retrospective evaluation of
      medical records of patients with severe cognitive impairment within the first
      five years of MS diagnosis. Results on neuropsychological tests and magnetic
      resonance imaging (MRI) were disclosed. Results: Four patients from different
      Brazilian neurological departments in Brazil were evaluated, all presenting with
      severe cognitive dysfunction classified as rapidly developing dementia. MRI
      images showed severe brain atrophy and basal ganglia lesions in all patients.
      Conclusions: Although rare, severe cognitive impairment in MS represents an
      important disability and may ultimately constitute another form of the disease.

PMID- 29213773
TI  - Life quality, depression and anxiety symptoms in chronic post-traumatic headache
      after mild brain injury.
AB  - : Post-traumatic headache (PTH) is the most common symptom found in the post
      traumatic syndrome, whose onset occurs within seven days of the trauma. The
      condition is characterized as acute when it persists for up to 3 months. PTH
      beyond this period is considered chronic. Objectives: The objective of this study
      was to determine the clinical features of chronic post-traumatic headache (cPTH)
      and its association with depression, anxiety and quality of life. Methods: A
      total of 73 female subjects were evaluated. Patients were divided into three
      groups: (a) group without headache, CONTROL, n=25; (b) cPTH group, n=19; and (c)
      MIGRAINE, n=29, with all subjects in the 11-84 year age group. Symptoms of
      anxiety and depression were evaluated by the Beck inventories of anxiety and
      depression, and quality of life assessed by the Lipp and Rocha quality of life
      inventory. Qualitative variables were analyzed using the Chi-square or Fisher's
      exact tests and expressed as percentages whereas quantitative variables were
      analyzed by ANOVA, Mann-Whitney or Kruskal-Wallis tests with data expressed as
      mean+/-standard deviation, p<0.05. Results: Subjects with cPTH presented with
      headache manifesting similar features to those found in migraine. The cPTH group
      was associated with similar levels of anxiety and depression to the migraine
      group and higher than the CONTROL (p<0.001). Quality of life of individuals with
      cPTH was similar to that of subjects with migraine and lower than CONTROL
      subjects (p<0.05). Conclusions: cPTH presents similar clinical characteristics to
      migraine. Subjects with cPTH had high levels of anxiety and depression symptoms
      and reduced quality of life.

PMID- 29213774
TI  - Acquired hepatocerebral degeneration: A case report.
AB  - Acquired hepatocerebral degeneration is an underdiagnosed neurologic syndrome
      characterized by parkinsonism, ataxia or other movement disorders and by
      neuropsychiatric and cognitive symptoms. It occurs in patients with chronic liver
      disease, especially those who develop portosystemic shunting and is often
      unrecognized as a cause of cognitive decline. Recently, its pathogenesis has been
      associated with manganese accumulation in basal ganglia and some treatments
      proposed. The aim of this article was to report a case and discuss some
      discoveries in connection with the disease.

PMID- 29213776
TI  - In the June 2012 issue.

PMID- 29213775
TI  - Frontotemporal dementia and neurocysticercosis: A case report.
AB  - We report a case of a 67-year-old woman with frontotemporal dementia (FTD) and a
      history of neurocysticercosis. After her retirement she showed progressive
      behavioral changes and neuropsychiatric symptoms with relative preservation of
      cognitive functioning. During the next three years, the patient manifested
      progressive deterioration of verbal communication gradually evolving to mutism, a
      hallmark of cases of progressive nonfluent aphasia.

PMID- 29213777
TI  - Cognitive impairment in migraine: A systematic review.
AB  - : Patients with migraine often report cognitive complaints, especially regarding
      attention and memory. Objective: To perform a systematic review of the studies
      available on cognitive evaluation in patients with migraine. Methods: We
      evaluated all articles containing the key words: "Migraine", "Cognition" and
      "Cognitive Impairment." Results: The search strategy resulted in 23 articles.
      Fifteen out of the 23 studies (65.3%) retrieved reported abnormalities on
      neuropsychological tests in migraine patients, notably tests of memory, attention
      and information processing speed. Most of the studies showing cognitive changes
      in migraine were carried out in neurological care facilities. Conversely, among
      community-based studies, migraine patients were less likely to present cognitive
      changes. Conclusion: Patients with migraine, especially those followed at
      neurology clinics, show an elevated risk of mild changes in several cognitive
      domains. Further studies with greater methodological refinement are warranted in
      order to clearly establish whether this cognitive dysfunction is associated with
      an underlying migraine pathophysiological process.

PMID- 29213778
TI  - The influence of diabetes mellitus II on cognitive performance.
AB  - Background: The association between diabetes mellitus and cognitive dysfunction
      is becoming increasingly clear, rendering it necessary for physicians in charge
      of diabetic patients to have the means to assess cognitive performance. Simple
      tests that can be applied during routine consultations may be useful for
      monitoring cognitive function during the course of diabetes. Objective: The
      objective of the present study was to assess cognition in diabetes mellitus type
      II (DM-II) using simple tests that can be incorporated into routine medical
      practice. Methods: A cross-sectional study including healthy controls and DM-II
      patients was carried out between May and September 2011. Volunteers aged 60 years
      and over were assessed by means of figure recognition, verbal fluency and the
      10*36 tests. Results: A group of 100 participants was divided into a subgroup of
      50 DM-II patients and a subgroup of 50 healthy volunteers. No statistical
      difference regarding demographic characteristics was found between the two
      groups. Results on the 10*36 test showed significantly worse performance among DM
      II patients (p<0.0001). Assessment of the DM-II subgroup in terms of disease
      duration showed statistically significant differences (p<0.001) on figure
      recognition and verbal fluency, with worse cognitive performance among
      individuals with longer disease duration, irrespective of gender or age.
      Conclusion: Figure recognition, verbal fluency and 10*36 tests are easy to apply
      and could be used in routine medical practice for the early detection of
      cognitive dysfunction among patients with DM-II.

PMID- 29213779
TI  - Screening for cognitive impairment in late onset depression in a Brazilian sample
      using the BBRC-Edu.
AB  - : Depression and dementia are the most prevalent neuropsychiatric disorders in
      the elderly population. Alzheimer's disease is the leading cause of dementia in
      most countries, being responsible for more than half of all dementia cases. Late
      onset depression is a frequent cause of cognitive decline in the elderly.
      Differentiating between cognitive impairment secondary to depression and
      incipient dementia poses a challenge in the clinical setting. Objective: To
      evaluate the performance of elderly depressed patients using the BBRC-Edu.
      Methods: We studied 25 patients with late onset depression (mean age: 73.6 y
      (6.6); schooling: 9.1 y (5.7)) and 30 patients with mild AD (mean age 76.6 y
      (5.4); schooling: 7.5 y (7.1)), who were compared to a control group of 30
      healthy elderly (mean age 73.8 y (5.8); schooling: 9.1 y (5.4)) using the CERAD
      and BBRC-Edu batteries. Results: For the CERAD battery, depressed patients
      performed better than AD patients on all tasks (p<0.0001) except for
      Constructional Praxis (p>0.05), and performed poorer than controls on verbal
      fluency (animals) and Word List Recall tasks (p<0.0001). For the BBRC-Edu,
      depressed patients performed better than AD patients on all tasks (p<0.0001)
      except for Digit Span (direct order) (p=0.076) and Incidental Memory (p>0.05),
      and performed worse than controls on Learning (second presentation) and verbal
      fluency (fruits) tasks (p<0.0001). Conclusion: Overall performance on the BBRC
      Edu allowed differentiation of controls and depressed patients from AD patients.

PMID- 29213780
TI  - Visual reproduction test in normal elderly: Influence of schooling and visual
      task complexity.
AB  - : Tests of visual reproduction are used to assess visual memory. However, when
      the test is based on geometrical elements results could be influenced by
      schooling. Objective: To evaluate the influence of different schooling levels on
      performance of a visual reproduction task. Methods: A sample of 253 individuals
      (66 male and 187 female), aged 60 to 92 years were evaluated on a visual
      reproduction task comprising three geometric pictures of increasing complexity.
      Each individual was shown a picture for 8 to 10 seconds and a drawing of it was
      then immediately elicited. Four groups were defined according to the following
      schooling levels: illiterate, 1 to 4 years, 5 to 8 years and over 8 years.
      Individual performance was measured by summing the items correctly reproduced for
      the three pictures. Results: A significant difference for age was found between
      the illiterate and other three schooling groups. The reproduction of picture one
      was better reproduced than pictures 2 and 3 for all schooling levels (p<0.001).
      Pictures 2 and 3 did not differ among the schooling levels. Picture reproduction
      among the schooling levels showed that the group with over 8 years of schooling
      performed better on pictures 1 and 2 (p<0.001) but not on picture 3. Conclusion:
      Individuals aged 60 years or older, with 8 years' schooling or less, showed a
      reduced capacity to reproduce geometric pictures of a high degree of complexity.
      Clinical evaluations that use geometrical tests could be misinterpreted when not
      controlled for schooling level.

PMID- 29213781
TI  - Neuropsychological performance differences between two groups of probable-AD
      patients from different areas of Brazil.
AB  - : During normal aging there are some cognitive and behavioral changes similar to
      those observed in a transitional state or mild cognitive impairment (MCI) and
      early onset dementia, making it challenging for health care professionals to
      reach an accurate and reliable diagnosis. Objective: The current study examined
      the performance of two different groups of patients diagnosed with probable
      Alzheimer's disease (AD) on a neuropsychological test battery. Methods: Twenty
      two AD patients from Brasilia-DF (AD1) and thirty-four AD patients from Palmas
      TO, northern Brazil (AD2), were selected and a short neuropsychological battery
      administered. To verify the reliability of these previous diagnoses of AD, both
      groups of patients were compared with a group of healthy controls. Results: AD
      patients showed cognitive deficit but scores were lower for the AD2 group
      compared with the AD1 group considering the cut-off point. Notably, patients from
      the AD1 group were older (p=0.004) and had less formal education (p<0.001) than
      those from the AD2 group. Comparing different cognitive domains between AD
      groups, post hoc analysis showed that the AD1 group was characterized by deficits
      in episodic memory retrieval (p<0.001), semantic memory (p<0.001) and verbal
      fluency (p<0.001). In contrast, the AD2 group showed lower scores in attention
      (p=0.007), executive functioning (p<0.001) and working memory (p<0.001).
      Conclusion: This pattern suggests that the Palma group of patients had a
      neuropsychological profile that was inconsistent with AD. Although the results of
      this study have important clinical implications, the effects of age, education,
      and gender on cognitive performance should be explored further.

PMID- 29213782
TI  - Brief reviews.

PMID- 29213783
TI  - In the September 2012 issue.

PMID- 29213784
TI  - Vascular dementia: Current concepts and nomenclature harmonization.
AB  - Several types of cerebrovascular lesions are associated with cognitive decline,
      but the role of each type in dementia manifestation has yet to be determined. One
      of the greatest barriers of conducting clinicopathological studies in vascular
      dementia concerns the overlapping of nomenclature for these lesions. The aim of
      the present review was to discuss current nomenclature for cerebrovascular
      lesions and suggest modifications to allow better diagnostic reproducibility in
      this field.

PMID- 29213785
TI  - Cognitive function and carotid stenosis: Review of the literature.
AB  - Stroke is a known cause of cognitive impairment but the relationship between
      asymptomatic carotid artery stenosis and cognitive function is not clear. The
      main risk factors for vascular disease are also related to carotid stenosis and
      cognitive impairment. The association of high-grade stenosis of the internal
      carotid artery with cognitive impairment is related to silent embolization and
      hypoperfusion, but it may also be present without evidence of infarction on
      magnetic resonance imaging. Carotid stenosis treatment may lead to a decline in
      cognitive function due to complications related to the procedures (endarterectomy
      or stenting). On the other hand, reperfusion may improve cognitive impairment.
      The best treatment choice is unclear, considering possible deterioration of
      cognitive function related to carotid artery stenosis. There is insufficient
      evidence to consider cognitive impairment an important factor in determining the
      therapy for carotid stenosis.

PMID- 29213786
TI  - Relationship between cortical microinfarcts and cognitive impairment in
      Alzheimer's disease.
AB  - Cerebrovascular disease and AD pathology co-exist in most dementia cases, and
      microinfarcts (MIs), particularly if cortical and multiple, play an additive and
      independent role in AD cognitive impairment. The main cause of cortical MIs is
      chronic cerebral hypoperfusion but occlusive vascular diseases, embolism and
      blood-brain barrier disruptions, isolated or combined, may also play a role. The
      precise mechanisms by which MIs cause cognitive impairment are not well known,
      but one plausible explanation is that they are widespread and accompanied by
      diffuse hypoperfusion, hypoxia, oxidative stress and inflammation, particularly
      in the watershed areas of the tertiary association cortex, and hence could damage
      cognition networks and explain many of AD's cognitive and behavioral
      disturbances. Therefore, it is crucial to control vascular risk factors and avoid
      uncontrolled use of the antihypertensives, neuroleptics and other sedative drugs
      frequently prescribed to AD patients.

PMID- 29213787
TI  - Vascular Parkinsonism and cognitive impairment: literature review, Brazilian
      studies and case vignettes.
AB  - Vascular Parkinsonism (VP) is a form of secondary Parkinsonism resulting from
      cerebrovascular disease. Estimates of the frequency of VP vary greatly worldwide;
      3% to 6% of all cases of Parkinsonism are found to have a vascular etiology. In a
      Brazilian community-based study on Parkinsonism, 15.1% of all cases were
      classified as VP, the third most common form, with a prevalence of 1.1% in an
      elderly cohort. Another Brazilian survey found a prevalence of 2.3% of VP in the
      elderly. VP is usually the result of conventional vascular risk factors,
      particularly hypertension, leading to strategic infarcts of subcortical gray
      matter nuclei, diffuse white matter ischaemic lesions and less commonly, large
      vessel infarcts. Patients with VP tend to be older and present with gait
      difficulties, symmetrical predominant lower-body involvement, poor levodopa
      responsiveness, postural instability, falls, cognitive impairment and dementia,
      corticospinal findings, urinary incontinence and pseudobulbar palsy. This article
      intends to provide physicians with an insight on the practical issues of VP, a
      disease potentially confounded with vascular dementia, idiopathic Parkinson's
      disease, dementia with Lewy bodies and other secondary causes of Parkinsonism.

PMID- 29213788
TI  - Dysexecutive syndrome and cerebrovascular disease in non-amnestic mild cognitive
      impairment: A systematic review of the literature.
AB  - Objective: Non-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI)
      may represent preclinical Vascular Dementia (VaD). The aim of this study was to
      summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and
      to assess its patterns of progression to dementia. Methods: Searches were made in
      the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild
      cognitive impairment" and "executive function". Altogether, 944 articles were
      retrieved. Results: VaMCI cases had poorer performances on fronto-executive
      tasks, a higher prevalence of stroke, presence of periventricular and profound
      white matter hyperintensities on MRI images, as well as more extrapyramidal signs
      and behavioral symptoms. Executive dysfunction might be associated with
      disconnection of fronto-parietal-subcortical circuits. Progression to dementia
      was associated with baseline deficits in executive function, in simple sustained
      attention and language, and large periventricular WMH. Discussion: VaMCI develops
      with impairment in non-memory domains and subcortical white matter changes on MRI
      images, which are consistent with clinical and neuroimaging findings in VaD.

PMID- 29213789
TI  - Association among depression, cognitive impairment and executive dysfunction
      after stroke.
AB  - : The relationship between depression and cognitive impairment, frequent after
      stroke, is complex and has not been sufficiently elucidated. Objective: To review
      the relationship between post-stroke depression and cognitive impairment.
      Methods: We performed a PubMed database search spanning the last ten years, using
      the terms post-stroke depression, cognitive dysfunction, cognitive impairment and
      neuropsychological tests. Our target studies were original quantitative studies
      that investigated the relationship between post-stroke depression (PSD) and
      cognitive impairment in stroke patients. Articles published in English, Spanish,
      Italian and Portuguese were considered. Selection criteria were the use of
      neuropsychological tests to assess cognitive function, and of either instruments
      to diagnose major depression, or scales to assess depressive symptoms, within the
      first three months after stroke. Results: Six original quantitative studies
      fulfilled the criteria. The prevalence of PSD within the first three months after
      stroke ranged from 22% to 31%. Incidence ranged from 25% to 27% and was evaluated
      in only two studies. PSD was associated with increased cognitive impairment.
      Cognitive impairment was reported in 35.2% to 87% of the patients. Post-stroke
      cognitive deficits were reported mostly in executive function, memory, language,
      and speed of processing. Conclusion: Executive dysfunction and depression occur
      in stroke survivors, are frequently coexistent, and also associated with worse
      stroke prognosis. Healthcare professionals need to address and provide adequate
      treatment for depression and executive dysfunctions in stroke patients early in
      the first three months after stroke. Future studies should evaluate the efficacy
      of programs evaluating the early detection and treatment of PSD and executive
      dysfunction in stroke survivors.

PMID- 29213790
TI  - Diffusion tensor imaging studies in vascular disease: A review of the literature.
AB  - : Cerebrovascular disease (CVD) is often present in old age and may be associated
      with microstructural pathology of white matter (WM) and cognitive dysfunction.
      The current review investigated the relationship between CVD, cognitive status
      and WM integrity as assessed by diffusion tensor imaging (DTI). Methods: DTI
      studies were searched on ISI and Pubmed databases from 2002 to 2012. Results:
      Studies evidenced DTI changes in WM as associated with vascular disease and
      provide increasing support for DTI as a valuable method for early detection of
      CVD. Conclusion: DTI parameters can serve as important biomarkers in monitoring
      vascular disease progression and treatment response and may represent a surrogate
      marker of WM tract integrity.

PMID- 29213791
TI  - Vascular Cognitive Impairment (VCI) after non-embolic ischemic stroke during a 12
      month follow-up in Brazil.
AB  - : VCI represents a spectrum of cognitive impairments associated with stroke,
      vascular brain injury, or subclinical disease ranging from the least to most
      severe manifestations. Few studies are available on the prevalence of post-stroke
      VCI and none have been conducted in Brazil. Objective: To determine the
      prevalence rates of VCI and associated risk factors in a sample of ischemic
      stroke patients. Methods: We evaluated 172 patients with ischemic stroke for
      cognitive impairment one year after ictus. Results: Patients comprised 81 women
      (47.1%) and had a mean age of 67.77 (7.86) years, schooling of 3.52 (2.99) years,
      and MMSE score of 24.94 (3.59) points. After cognitive evaluation, 4.6% were
      diagnosed as CIND (cognitive impairment no dementia) and 12.2% had a diagnosis of
      dementia (probable vascular dementia in 20 patients and one subject with
      cerebrovascular disease and Alzheimer's disease). Conclusion: The prevalence of
      dementia was lower than previous reports but our sample had a lower age than
      others, while a 12 month-period of follow-up prevented interference from
      associated neurodegenerative disorders.

PMID- 29213792
TI  - NEUROPSI battery subtest profile in subcortical vascular dementia and Alzheimer's
      disease.
AB  - Objective: To investigate the diagnostic value of subtests of the NEUROPSI
      battery for differentiating subcortical vascular dementia (SVaD) from Alzheimer's
      disease (AD). Methods: Thirteen patients with mild SVaD, 15 patients with mild
      probable AD, and 30 healthy controls, matched for age, education and dementia
      severity (in the case of patients), were submitted to the Mini-Mental State
      Examination (MMSE) and NEUROPSI battery. The performance of AD and SVaD groups on
      NEUROPSI subtests was compared. The statistical analyses were performed using
      Kruskal-Wallis, Chi-square and Mann-Whitney tests. The results were interpreted
      at the 5% significance level (p<0.05). Bonferroni's correction was applied to
      multiple comparisons (alpha=0.02). Results: SVaD and AD patients showed no
      statistical difference in MMSE scores (SVaD=20.8 and AD=21.0; p=1.0) or in
      NEUROPSI total score (SVaD=65.0 and AD=64.3; p=0.56), suggesting a similar
      severity of dementia. The AD group performed worse on memory recall (<0.01) and
      SVaD group was worse in verbal fluency subtests (p=0.02). Conclusion: NEUROPSI's
      memory and language subtests can be an auxiliary tool for differentiating SVaD
      from AD.

PMID- 29213793
TI  - Behavioral and psychological symptoms and hippocampal atrophy in subcortical
      ischaemic vascular disease.
AB  - Background: Neuropsychiatric symptoms are common in patients with cognitive
      impairments, mediated by both neurodegenerative processes and cerebrovascular
      disease. Previous studies have reported that Behavioral and Psychological
      Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline.
      Thus far, the impact of the association between white-matter hyperintensities
      (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been
      less studied. Objective: This cross-sectional study aimed to describe the
      clinical profile of a sample with large extensions of WMH, examining the
      association between different degrees of HA and cognitive, functional, and
      behavioral status. Methods: Fifty outpatients (mean age: 76.86+/-8.70 years; 58%
      female; mean schooling: 7.44+/-4.69 years) with large extensions of WMH (modified
      Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according
      to de Leon Score) underwent cognitive, functional, and behavioral assessments.
      Results: Patients with mild-moderate to severe HA had worse performance on the
      Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia
      Rating and Pfeffer's Functional Activities Questionnaire, compared to the group
      with none or questionable HA. Appetite/Eating Behavior was the only cluster of
      neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive
      Impairment patients. Discussion: Although HA may exhibit distinct impact on
      cognitive performance and functional status, it appears to have little effect on
      behavioral symptoms in patients with high severity WMH.

PMID- 29213795
TI  - CADASIL: case report.
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) is a hereditary cerebral arteriopathy caused by
      mutations in the Notch-3 gene. The diagnosis is reached by skin biopsy revealing
      presence of granular osmiophilic material (GOM), and/or by genetic testing for
      Notch-3. We report a case of a 52-year-old man with recurrent transient ischemic
      attacks (TIA), migraine, in addition to progressive sensory, motor and cognitive
      impairment. He was submitted to a neuropsychological assessment with the CERAD
      (Consortium to Establish a Registry for Alzheimer's Disease) battery along with
      other tests, as well as neuroimaging and genetic analysis for Notch-3, confirming
      the diagnosis. Executive function, memory, language and important apraxic changes
      were found. Imaging studies suggested greater involvement in the frontal lobes
      and deep areas of the brain.

PMID- 29213794
TI  - Clinical assessment, neuroimaging and immunomarkers in Chagas disease study
      (CLINICS): Rationale, study design and preliminary findings.
AB  - : Chagas disease (CD) is an important cause of cardiomyopathy and stroke in
      Brazil. Brain infarcts and atrophy seem to occur independently of cardiomyopathy
      severity and cognitive impairment is understudied. Objective: Compare the
      prevalence of brain magnetic resonance imaging abnormalities between patients
      with or without CD; determine if inflammatory biomarkers are increased in CD; and
      determine the efficacy of aspirin in reducing the rate of microembolization in
      these patients. Methods: 500 consecutive patients with heart failure will undergo
      a structured cognitive evaluation, biomarker collection and search for
      microembolic signals on transcranial Doppler. The first 90 patients are
      described, evaluated with cognitive tests and brain magnetic resonance imaging to
      measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatine
      (Cr). Results: Mean age was 55+/-11 years, 51% female, 38 (42%) with CD. Mean
      NAA/Cr ratio was lower in patients with CD as compared to other cardiomyopathies.
      Long-term memory and clock-drawing test were also significantly worse in CD
      patients. In the multivariable analysis correcting for ejection fraction, age,
      sex and educational level, reduced NAA/Cr (p=0.006) and cognitive dysfunction
      (long-term memory, p=0.023; clock-drawing test, p=0.015) remained associated with
      CD. Conclusion: In this preliminary sample, CD was associated with cognitive
      impairment and decreased NAA/Cr independently of cardiac function or educational
      level.

PMID- 29213796
TI  - Vascular cognitive impairment in Pemphigus vulgaris: A case report.
AB  - Pemphigus vulgaris is a systemic auto-immune medical condition that mainly
      manifests with changes in skin and vasculopathy. This is a case report of a 69
      year-old male with confirmed histopathologic diagnosis of Pemphigus vulgaris
      presenting ulterior Cognitive Impairment, mostly in executive function. The
      patient was treated using steroids, immunomodulatory therapy, fluoxetine and
      galantamine. Neuropsychological testing and magnetic resonance (MRI) were
      performed. This is the first report of correlational cognitive impairment with
      Pemphigus vulgaris in the literature. Physicians should be aware of vascular
      causes for cognitive impairment in patients presenting auto-immune conditions.

PMID- 29213797
TI  - In the December 2012 issue.

PMID- 29213798
TI  - Occupational health, cognitive disorders and occupational neuropsychology.
AB  - Work can be an important etiologic factor in the genesis of some mental disorders
      including cognitive disability. Occupational neuropsychology constitutes an
      intriguing new but neglected area of research and clinical practice which deals
      with the neurocognitive consequences of the work environment and work habits.
      Neuropsychological knowledge is fundamental to understand cognitive requirements
      of work competence. Work can impact sleep patterns and mental energy, which in
      turn can cause neuropsychological symptoms. This report presents relevant
      evidence to illustrate the relationship between work and cognitive dysfunction.

PMID- 29213799
TI  - Relationship between structural abnormalities in the cerebellum and dementia,
      posttraumatic stress disorder and bipolar disorder.
AB  - : New evidence suggests that the cerebellum has structural and functional
      abnormalities in psychiatric disorders. Objective: In this research, the goal was
      to measure the volume of the cerebellum and its subregions in individuals with
      psychiatric disorders and to relate these findings to their symptoms. Methods:
      Patients with different degrees of cognitive impairment (Epidemiology of the
      Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from
      population studies were analyzed. Also, patients with bipolar disorder from an
      outpatient clinic (Center for the Study of Mood and Anxiety Disorders,
      Universidade Federal da Bahia) were recruited for this study. All subjects
      underwent a 1.5T structural magnetic resonance scan. Volumetric measures and
      symptom measurements, by psychometric scales, were performed and compared between
      patients and controls. Results: The cerebellum volume was reduced in patients
      with cognitive impairment without dementia and with dementia, in patients with
      PTSD, and in patients with bipolar disorder compared to controls. In dementia and
      PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar
      disorder, volumes of both hemispheres and the vermis were reduced. In the first
      two studies, these cerebellar volumetric reductions correlated with symptoms of
      the disease. Conclusion: The exact nature of cerebellar involvement in mental
      processes is still not fully understood. However, abnormalities in cerebellar
      structure and its functions have been reported in some of these diseases. Future
      studies with larger samples are needed to clarify these findings and investigate
      whether they are important for treatment and prognosis.

PMID- 29213800
TI  - Memory complaint scale (MCS). Proposed tool for active systematic search.
AB  - : Subjective Memory Complaints (SMC) are frequent among adults and elderly and
      are associated with poor quality of life. The etiology and clinical significance
      of SMCs are unclear, but these complaints are associated with objective cognitive
      decline or with depression, anxiety and psychosocial stressors. Biological and
      physiological brain alterations resembling those in Alzheimer's Disease have been
      found in SMC. SMC can evolve with different outcomes and represent the initial
      symptom or a risk factor of dementia. Active systematic search can be useful for
      early screening of candidates for preventive or therapeutic interventions.
      Objective: To propose a Memory Complaints Scale (MCS) as an instrument for
      actively searching for memory complaints and to investigate its utility for
      discriminating demented from cognitively normal elderly. Methods: A total of 161
      patients from a teaching behavioral neurology outpatient unit of a tertiary
      hospital were studied. The MCS was used in two ways, by direct application to the
      patient and by application to the patient's companion. Cognitive tests assessing
      depression and daily living activities were also applied. Results: High
      Cronbach's alpha coefficients were found for the two application methods.
      Correlations between the two versions and the other instruments administered for
      patients grouped by type and severity of dementia were also found. Conclusion:
      The MCS is a useful scale for identifying memory complaints and discriminating
      demented from cognitively normal elderly. Further studies confirming these
      findings are warranted.

PMID- 29213801
TI  - Systematic review of the literature on vitamin A and memory.
AB  - Background: Over the last 30 years, a variety of studies reporting the effects of
      vitamin A on memory have been published. Objective: To perform a rigorous
      systematic review of the literature on vitamin A and memory in order to organize
      evidence-based data on the subject. Methods: Four authors carried out the
      systematic review in accordance with strict guidelines. The terms "vitamin A" OR
      "retinol" OR "retinoic acid" AND "memory" OR "cognition" OR "Alzheimer" were
      searched in virtually all medical research databases. Results: From 236 studies
      containing the key words, 44 were selected for this review, numbering 10 reviews
      and 34 original articles. Most studies used animal models for studying vitamin A
      and cognition. Birds, mice and rats were more frequently employed whereas human
      studies accounted for only two reports on brain tissue from autopsies and one on
      the role of isotretinoin in cognition among individuals taking this medication to
      treat acne. Conclusion: Vitamin A may be an important and viable complement in
      the treatment and prevention of Alzheimer's disease. Clinical trials are
      imperative and, at present, there is no evidence-based data to recommend vitamin
      A supplementation for the prevention or treatment of Alzheimer's disease.

PMID- 29213802
TI  - Rehabilitation of language in expressive aphasias: a literature review.
AB  - Objective: This paper reviews the methodological characteristics of studies on
      rehabilitation of expressive aphasia, describing the techniques of rehabilitation
      used. Methods: The databases Medline, Science Direct and PubMed were searched for
      relevant articles (January 1999 to December 2011) using the keywords Expressive /
      Broca / Nonfluent Aphasia, combined with Language or Speech Rehabilitation /
      Therapy / Intervention. Results: A total of 56 articles were retrieved describing
      rehabilitation techniques, including 22 with a focus on lexical processing, 18 on
      syntax stimulation, seven with the aim of developing speech and nine with
      multiple foci. Conclusion: A variety of techniques and theoretical approaches are
      available, highlighting the heterogeneity of research in this area. This
      diversity can be justified by the uniqueness of patients' language deficits,
      making it difficult to generalize. In addition, there is a need to combine the
      formal measures of tests with measures of pragmatic and social skills of
      communication to determine the effect of rehabilitation on the patient's daily
      life.

PMID- 29213803
TI  - Apathy, cognitive function and motor function in Alzheimer's disease.
AB  - : The aims of this study were to characterize the presence of apathy in patients
      with AD, determine the relationship between apathy, motor function and cognitive
      function, and to verify differences among patients stratified by level of apathy
      in relation to cognitive and motor abilities. Methods: A cross-sectional study
      was conducted of 37 patients with AD. The following tests were used: MoCA, the
      Frontal Assessment Battery, Verbal Fluency, Clock Drawing Test, Andreotti & Okuma
      Battery Tests, Sit and Reach, Resistance of Upper Limbs - AAHPERD Battery Test,
      Sit and Lift Chair and the Apathy domain of the Neuropsychiatric Inventory. After
      verifying the normality of the data distribution, comparisons were made using
      Student's t-test and the U Mann Whitney test; relationships were also assessed
      using Pearson's and Spearman's correlation coefficients. All analyses were
      considered to be statistically significant at a p-value of 0.05. Results: 46% of
      participants in this study showed mild symptoms of apathy. Significant and weak
      associations were found (p=0.04) between apathy and the attention domain on the
      MoCA and between apathy and the Walk Test. Analysis of differences in cognitive
      and motor functions according to participants' level of apathy revealed no
      significant differences for any of the variables. Conclusion: Apathy was
      reflected in attention and the Walk Test, suggesting these variables may be
      related to cognitive and functional decline in AD patients.

PMID- 29213804
TI  - Montreal Battery of Evaluation of Amusia: Validity evidence and norms for
      adolescents in Belo Horizonte, Minas Gerais, Brazil.
AB  - The Montreal Battery of Evaluation of Amusia (MBEA) is a battery of tests that
      assesses six music processing components: scale, contour, interval, rhythm,
      metric, and music memory. The present study sought to verify the psychometric
      characteristics of the MBEA in a sample of 150 adolescents aged 14-18 years in
      the city of Belo Horizonte, Minas Gerais, Brazil, and to develop specific norms
      for this population. We used statistical procedures that explored the dimensional
      structure of the MBEA and its items, evaluating their adequacy from empirical
      data, verifying their reliability, and providing evidence of validity. The
      results for the difficult levels for each test indicated a trend toward higher
      scores, corroborating previous studies. From the analysis of the criterion
      groups, almost all of the items were considered discriminatory. The global score
      of the MBEA was shown to be valid and reliable (rK-R20=0.896) for assessing the
      musical ability of normal teenagers. Based on the analysis of the items, we
      proposed a short version of the MBEA. Further studies with larger samples and
      amusic individuals are necessary to provide evidence of the validity of the MBEA
      in the Brazilian milieu. The present study brings to the Brazilian context a tool
      for diagnosing deficits in musical skills and will serve as a basis for
      comparisons with single case studies and studies of populations with specific
      neuropsychological syndromes.

PMID- 29213805
TI  - Effects of weight training on cognitive functions in elderly with Alzheimer's
      disease.
AB  - : Deterioration in cognitive functions is characteristic in Alzheimer's disease
      (AD) and may be associated with decline in daily living activities with
      consequent reduced quality of life. Objective: To analyze weight training effects
      on cognitive functions in elderly with AD. Subjects: 34 elderly with AD were
      allocated into two groups: Training Group (TG) and Social Gathering Group (SGG).
      Methods: Global cognitive status was determined using the Mini-Mental State Exam.
      Specific cognitive functions were measured using the Brief Cognitive Battery,
      Clock Drawing Test and Verbal Fluency Test. The protocols were performed three
      times a week, one hour per session. The weight training protocol consisted of
      three sets of 20 repetitions, with two minutes of rest between sets and
      exercises. The activities proposed for the SGG were not systematized and aimed at
      promoting social interaction among patients. The statistical analyses were
      performed with the U Mann Whitney and Wilcoxon tests for group comparisons. All
      analyses were considered statistically significant at a p-value of 0.05. Results:
      There were no significant differences associated to the effects of the practice
      of weight training on cognition in AD patients. Conclusion: In this study, no
      improvement in cognitive functions was evident in elderly with AD who followed a
      low intensity resistance exercise protocol. Thus, future studies could evaluate
      the effect of more intense exercise programs.

PMID- 29213806
TI  - Neuropsychological and quality of life assessment in patients with Parkinson's
      disease submitted to bilateral deep brain stimulation in the subthalamic nucleus.
AB  - : Deep brain stimulation (DBS) has been widely used to control motor symptoms and
      improve quality of life in patients with Parkinsons disease (PD). Recently, DBS
      in the subthalamic nucleus (STN) has become the preferred target for patients
      with mixed motor symptoms. Despite resultant motor and quality of life
      improvements, the procedure has been associated with cognitive decline, mainly in
      language skills, and also with psychiatric symptoms. Objective: To evaluate the
      influence of DBS in the STN on cognition, mood and quality of life. Methods: We
      studied 20 patients with PD submitted to DBS in the STN from May 2008 to June
      2012 with an extensive battery of cognitive tests including memory, language,
      praxis, executive functions and attention assessments; the Parkinson's Disease
      Quality of Life Questionnaire (PDQ-39); and the Hospital Anxiety and Depression
      Scale (HAD), were applied both before and after the surgery. Data was analyzed
      using SPSS version 17.0 and results compared using the paired Student's t test.
      Results: A total of 20 patients with pre and post-operative assessments were
      included. A statistically significant improvement was found in total score and on
      subscales of mobility, activities of daily living and emotional well-being from
      the PDQ-39 (P=0.009, 0.025, 0.001 and 0.034, respectively). No significant
      difference was found on the cognitive battery or mood scale. Conclusion: DBS in
      the SNT improved quality of life in PD with no negative impact on cognitive
      skills and mood.

PMID- 29213807
TI  - Cognitive impairment in patients with clinically isolated syndrome.
AB  - : Cognitive abnormalities have been extensively studied in Multiple Sclerosis
      (MS). However, little is known about the cognitive involvement in patients with
      Clinically Isolated Syndrome (CIS). Objective: This study aimed to investigate
      cognitive impairment in patients with CIS compared with healthy subjects.
      Methods: 18 CIS patients and 18 controls were subjected to the Wechsler memory
      scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial
      Addition, Digit Span, verbal fluency, Stroop color card test, D2, and Digit
      Symbol tests. Results: CIS patients had significantly worse performance on the
      Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and on verbal
      fluency tests (P=0.0038) than controls. Conclusion: CIS patients had worse
      cognitive performance than controls on neuropsychological tests evaluating
      executive functioning.

PMID- 29213808
TI  - Reassessment of the dementia diagnosis of Alzheimer's disease in patients
      enrolled on the cholinesterase inhibitors dispensation program.
AB  - Objective: Reassess the diagnosis of Alzheimer's Disease (AD) in patients treated
      with anti-cholinesterases dispensed by High Cost Drug stores (Exceptional Drugs
      Program). Methods: A prospective study to reassess the diagnosis of probable
      Alzheimer's Disease was conducted (AD). The patients were submitted to the
      protocol of dementia investigation at the Neurogeriatric Outpatient Clinic of the
      Teaching Hospital de Base de Sao Jose do Rio Preto. Groups were classified using
      the criteria of the National Institute of Neurologic and Communicative Diseases
      and Vascular Cerebral Accident and Alzheimer Disease Related Association (NINCDS
      ADRDA). The study was completed by applying the Disability Assessment for
      Dementia (DAD). The significance level was set at 5%. Results: 106 patients
      participated, selected randomly from a group of 390 patients contacted when
      receiving their medication at the High Cost Drug store. Two groups were formed:
      the first, containing 52 patients who fulfilled criteria for AD (FC Group); and a
      second, with 54 patients not fulfilling criteria (NFC). The FC Group had older
      age, worse performance on the Mini-Mental State Exam (MMSE) and poorer
      performance on the DAD. Also, treatment time was longer and drugs doses higher in
      the FC Group. Conclusion: Study results showed a high number of patients using
      anti-cholinesterases that did not fulfill the diagnosis criteria for probable AD.
      Comparison of the two groups revealed different behavior between them,
      corroborating the hypothesis of inadequate inclusion of the NFC Group patients in
      the Exceptional Drugs Program.

PMID- 29213809
TI  - Participation in nighttime activities in the genesis of depression in public
      school teachers from the State of Pernambuco, Brazil.
AB  - : Teachers often undertake nighttime work involving exam corrections, projects
      and devising lesson plans in their homes. Many present excessive daytime
      sleepiness (EDS) and depression. Objective: The objective of this study was to
      evaluate EDS and depression in teachers from public schools. Methods: 201 female
      teachers were evaluated in the district of Quipapa/PE, Brazil. Among the study
      sample, 38 working 1 shift (CONTROL 1), 40 working 2 shifts (CONTROL 2) and 123
      working 3 shifts (WTeachers-3T). The subjects were submitted to evaluation by the
      Epworth Sleepiness Scale and Beck Depression Inventory (BDI).The EDS data were
      analyzed by the Kruskal-Wallis test with Dunn's multiple comparison, p<0.05and
      expressed in MEDIAN (MINIMUM - MAXIMUM) whereas the depression data were analyzed
      by the Chi-square test, with p<0.05, expressed in percentage. Results: WTeachers
      3T presented excessive daytime sleepiness and higher rates of mild (24%) and
      moderate (37%) depression compared to controls - Control 1: mild (8%) and
      moderate (11%) - Control 2: mild (5%) and moderate (15%). Conclusion: This study
      found that teachers in the Quipapa municipality of Penambuco state working three
      shifts showed excessive daytime sleepiness and a higher percentage of mild and
      moderate depression compared to teachers working only one (1) or two (2) shifts.

PMID- 29213810
TI  - Basal ganglia lesions in subacute sclerosing panencephalitis.
AB  - The parieto-occipital region of the brain is the most frequently and severely
      affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia,
      cerebellum and corpus callosum are less commonly involved. We describe a patient
      with SSPE confirmed by neuropathology based on brain magnetic resonance imaging
      showing extensive basal ganglia involvement and no significant involvement of
      other cortical structures. Though rarely described in SSPE, clinicians should be
      aware of this involvement. SSPE should be kept in mind when changes in basal
      ganglia signal are seen on brain magnetic resonance imaging with or without
      involvement of other regions of the human brain to avoid erroneous etiological
      diagnosis of other pathologies causing rapidly progressive dementia.

PMID- 29213811
TI  - Adult-onset adrenoleukodystrophy presenting as a psychiatric disorder: MRI
      findings.
AB  - A 35-year-old, previously healthy man presented psychiatric symptoms lasting four
      years, receiving treatment with neuroleptics. One year later he evolved with gait
      disequilibrium. After a further six months, cognitive symptoms were characterized
      with rapid evolution to a profound demented state. MRI showed signal changes in
      cerebral white matter and very long-chain fatty acids were detected in blood.

PMID- 29213813
TI  - In the March 2013 issue.

PMID- 29213814
TI  - Behavioural-variant frontotemporal dementia: an update.
AB  - Behavioural-variant frontotemporal dementia (bvFTD) is characterised by insidious
      changes in personality and interpersonal conduct that reflect progressive
      disintegration of the neural circuits involved in social cognition, emotion
      regulation, motivation and decision making. The underlying pathology is
      heterogeneous and classified according to the presence of intraneuronal
      inclusions of tau, TDP-43 or occasionally FUS. Biomarkers to detect these
      histopathological changes in life are increasingly important with the development
      of disease-modifying drugs. Gene mutations have been found which collectively
      account for around 10-20% of cases including a novel hexanucleotide repeat on
      chromosome 9 (C9orf72). The recently reviewed International Consensus Criteria
      for bvFTD propose three levels of diagnostic certainly: possible, probable and
      definite. Detailed history taking from family members to elicit behavioural
      features underpins the diagnostic process with support from neuropsychological
      testing designed to detect impairment in decision-making, emotion processing and
      social cognition. Brain imaging is important for increasing the level of
      diagnosis certainty. Carer education and support remain of paramount importance.

PMID- 29213815
TI  - Neuropathology of frontotemporal lobar degeneration: a review.
AB  - Frontotemporal lobar degeneration (FTLD) is the second most common cause of
      presenile dementia. Three main clinical variants are widely recognized within the
      FTLD spectrum: the behavioural variant of frontotemporal dementia (bvFTD),
      semantic dementia (SD) and progressive non-fluent aphasia (PNFA). FTLD represents
      a highly heterogeneous group of neurodegenerative disorders which are best
      classified according to the main protein component of pathological neuronal and
      glial inclusions. The most common pathological class of FTLD is associated with
      the TDP-43 protein (FTLD-TDP), while FTLD-Tau is considered slightly less common
      while the FTLD-FUS (Fused in sarcoma protein) pathology is rare. In this review,
      these three major pathological types of FTLD are discussed.

PMID- 29213816
TI  - Prevalence of frontotemporal dementia in community-based studies in Latin
      America: a systematic review.
AB  - : Latin America (LA) is experiencing a rise in the elderly population and a
      consequent increase in geriatric problems such as dementia. There are few
      epidemiological studies assessing the magnitude of dementia and dementia subtypes
      in LA. OBJECTIVE: To identify published community-based studies on the prevalence
      of FTD in LA countries. METHODS: A database search for door-to-door studies on
      FTD prevalence in LA was performed. The search was carried out on Medline,
      Embase, and LILACS databases for research conducted between 1994 and 2012. The
      main inclusion criteria were: use of any internationally accepted diagnostic
      criteria and investigation of community samples. RESULTS: Four hundred and ninety
      two articles were found, of which 26 were initially pre-selected by title or
      abstract review. Five studies from 3 different countries were included. The FTD
      prevalence rates in community-dwelling elderly were 1.2 (Venezuela), 1.3 (Peru)
      and 1.7-1.8 (Brazil) per thousand persons, depending on age group. CONCLUSION:
      The FTD prevalence in LA studies showed values mid-way between those observed in
      western and in oriental populations. Despite the magnitude of this problem,
      epidemiological information on FTD remains scarce in LA.

PMID- 29213817
TI  - The INECO Frontal Screening tool differentiates behavioral variant -
      frontotemporal dementia (bv-FTD) from major depression.
AB  - : Executive dysfunction may result from prefrontal circuitry involvement
      occurring in both neurodegenerative diseases and psychiatric disorders. Moreover,
      multiple neuropsychiatric conditions, may present with overlapping behavioral and
      cognitive symptoms, making differential diagnosis challenging, especially during
      earlier stages. In this sense, cognitive assessment may contribute to the
      differential diagnosis by providing an objective and quantifiable set of measures
      that has the potential to distinguish clinical conditions otherwise perceived in
      everyday clinical settings as quite similar. OBJECTIVE: The goal of this study
      was to investigate the utility of the INECO Frontal Screening (IFS) for
      differentiating bv-FTD patients from patients with Major Depression. METHODS: We
      studied 49 patients with bv-FTD diagnosis and 30 patients diagnosed with unipolar
      depression compared to a control group of 26 healthy controls using the INECO
      Frontal Screening (IFS), the Mini Mental State Examination (MMSE) and the
      Addenbrooke's Cognitive Examination-Revised (ACE-R). RESULTS: Patient groups
      differed significantly on the motor inhibitory control (U=437.0, p<0.01), verbal
      working memory (U=298.0, p<0.001), spatial working memory (U=300.5, p<0.001),
      proverbs (U=341.5, p<0.001) and verbal inhibitory control (U=316.0, p<0.001)
      subtests, with bv-FTD patients scoring significantly lower than patients with
      depression. CONCLUSION: Our results suggest the IFS can be considered a useful
      tool for detecting executive dysfunction in both depression and bv-FTD patients
      and, perhaps more importantly, that it has the potential to help differentiate
      these two conditions.

PMID- 29213818
TI  - Chilean version of the INECO Frontal Screening (IFS-Ch): psychometric properties
      and diagnostic accuracy.
AB  - OBJECTIVE: This study sought to analyze the psychometric properties and
      diagnostic accuracy of the Chilean version of the INECO Frontal Screening (IFS
      Ch) in a sample of dementia patients and control subjects. METHODS: After
      adapting the instrument to the Chilean context and obtaining content validity
      evidence through expert consultation, the IFS-Ch was administered to 31 dementia
      patients and 30 control subjects together with other executive assessments
      (Frontal Assessment Battery [FAB], Modified version of the Wisconsin Card Sorting
      Test [MCST], phonemic verbal fluencies [letters A and P] and semantic verbal
      fluency [animals]) and global cognitive efficiency tests (Mini mental State
      Examination [MMSE] and Addenbrooke's Cognitive Examination-Revised [ACE-R]).
      Caregivers of dementia patients and proxies of control subjects were interviewed
      with instruments measuring dysexecutive symptoms (Dysexecutive Questionnaire
      [DEX]), dementia severity (Clinical Dementia Rating Scale [CDR]) and functional
      status in activities of daily living (Activities of Daily Living Scale [IADL] and
      Technology-Activities of Daily Living Questionnaire [T-ADLQ]). Convergent and
      discriminant validity, internal consistency reliability, cut-off points,
      sensitivity and specificity for the IFS-Ch were estimated. RESULTS: Evidence of
      content validity was obtained. Evidence of convergent validity was also found
      showing significant correlations (p<0.05) between the IFS-Ch and the other
      instruments measuring: executive functions (FAB, r=0.935; categories achieved in
      the MCST, r=0.791; perseverative errors in the MCST, r= -0.617; animal verbal
      fluency, r=0.728; "A" verbal fluency, r=0.681; and "P" verbal fluency, r=0.783),
      dysexecutive symptoms in daily living (DEX, r= -0.494), dementia severity (CDR,
      r= -0.75) and functional status in activities of daily living (T-ADLQ, r= -0.745;
      IADL, r=0.717). Regarding reliability, a Cronbach's alpha coefficient of 0.905
      was obtained. For diagnostic accuracy, a cut-off point of 18 points
      (sensitivity=0.903; specificity=0.867) and an area under curve of 0.951 were
      estimated to distinguish between patients with dementia and control subjects.
      DISCUSSION: The IFS-Ch showed acceptable psychometric properties, supported by
      evidence of validity and reliability for its use in the measurement of executive
      functions in patients with dementia. The diagnostic accuracy of the IFS-Ch for
      detecting dementia patients was also considered acceptable.

PMID- 29213819
TI  - Semantic memory: nouns and action verbs in cognitively unimpaired individuals and
      frontotemporal lobar degeneration.
AB  - : Among the instruments to evaluate semantic memory, the Pyramids and Palm Trees
      (PPT) and the Kissing and Dancing (KDT) tests are widely used but none have a
      performance referential for cognitively normal and impaired Brazilian
      populations. OBJECTIVE: [A] To study these two tests in a sample of young healthy
      Brazilian individuals living in Sao Paulo; [B] To apply the results to the
      evaluation of two cases diagnosed with frontotemporal lobar degeneration.
      METHODS: We evaluated 50 normal participants (41 females and 9 males) aged
      between 20-63 years, with schooling level of 14-20 years. In addition, two
      individuals diagnosed with frontotemporal lobar degeneration were examined, one
      with behavioral-variant frontotemporal dementia and the other with semantic
      dementia. RESULTS: On the two tests, no effects of age, gender and schooling on
      the performance of normal individuals were observed. According to the performance
      of the sample of controls, scores below 46 points on the PPT and below 47 on the
      KDT are suggestive of deficits in semantic memory. The analyses of both cases
      indicated double dissociation in establishing associations between nouns and
      action verbs. Although the two patients had low scores on both tests, the patient
      with behavioral-variant frontotemporal dementia performed better on the PPT
      compared to the KDT, while the patient with semantic dementia showed the reverse,
      performing better on the KDT. CONCLUSION: The PPT and KDT are suitable tests for
      use in the Brazilian population, with minimal need for adjustments. They are
      applicable tools both for cognitive assessment and research in semantic memory.
      In the present study, we obtained representative values of performance for
      cognitively unimpaired individuals and demonstrated the utility of these
      instruments for cognitive assessment of patients with FTLD.

PMID- 29213820
TI  - Analysis of a case series of behavioral variant frontotemporal dementia: emphasis
      on diagnostic delay.
AB  - INTRODUCTION: Despite many advances in the characterization of the behavioral
      variant of frontotemporal dementia (bvFTD), the diagnosis of this syndrome poses
      a significant challenge, while delays or diagnostic mistakes may impact the
      proper clinical management of these patients. OBJECTIVE: To describe the clinical
      profile at first evaluation of a sample of patients with bvFTD from a specialized
      outpatient neurological unit, with emphasis on the analysis of the delay between
      the onset of symptoms and diagnosis. METHODS: We selected 31 patients that
      fulfilled international consensus criteria for possible or probable bvFTD.
      Patients' medical admission sheets were thoroughly reviewed. RESULTS: Patients'
      mean age was 67.9+/-8.2 years; 16 (51.6%) were men. Mean number of years of
      formal education was 7.7+/-4.0 years. Mean age at onset was 62.2+/-7.7 years,
      indicating a mean of 5.8 years of diagnostic delay. Thirteen patients (41.9%)
      presented with initial behavioral complaints only, eleven patients (35.5%) had
      mixed behavioral and memory complaints, five patients (16.1%) presented with
      memory complaints only, and two patient (6.4%) had behavioral and speech
      problems. Nine patients (29%) were admitted with alternative diagnoses. Mean and
      standard deviation scores for the mini-mental state examination, animal category
      fluency and memory test for drawings (five-minute delayed recall) were 19.3+/
      6.3, 8.3+/-4.1and 3.7+/-2.7, respectively. CONCLUSION: Most patients from this
      sample were evaluated almost six years after the onset of symptoms and performed
      poorly on both cognitive screening tests and functional evaluation measures.

PMID- 29213821
TI  - Evaluation of patients with behavioral and cognitive complaints: misdiagnosis in
      frontotemporal dementia and Alzheimer's disease.
AB  - BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous clinicopathological
      syndrome whose early diagnosis is critical for developing management strategies.
      OBJECTIVE: To analyze the variables associated with misdiagnosis in a group of
      patients with FTD, Alzheimer's disease (AD), and without neurodegenerative
      disorders (WND), all of whom were evaluated for behavioral and cognitive
      complaints. METHODS: A case-control study with FTD (n=10), probable AD (n=10) and
      WND (n=10) patients was carried out. The studied variables were disease duration,
      reason for referral, former diagnosis, behavioral and cognitive symptoms at
      evaluation, MMSE at the specialist evaluation, and follow-up outcome. The data
      were analyzed by ANOVA with Bonferroni post-hoc and by Pearson's Chi-Square
      tests. RESULTS: FTD patients and WND patients showed longer disease duration than
      AD patients; the main reasons for referral in the FTD group were behavioral,
      memory and memory plus language problems while all AD and 90% of the WND group
      were referred for memory. The FTD group had the highest rate of misdiagnosis and
      worst outcomes after the 12-month follow-up. The majority of AD and WND patients
      had memory symptoms, while FTD patients presented language (30%), memory and/or
      language (40%) problems on the evaluation. CONCLUSION: Difficulty in recognizing
      the main features of FTD and psychiatric disorders with memory impairment was
      observed. Clinicians tended to generalize memory complaints toward a single
      diagnosis, identifying almost all these patients as AD or leaving them
      undiagnosed.

PMID- 29213822
TI  - Frontal presentation of Alzheimer's disease: a series of patients with biological
      evidence by CSF biomarkers.
AB  - Besides its typical amnesic presentation, focal atypical presentations of
      Alzheimer's disease (AD) have been described in neuropathological studies. These
      phenotypical variants of AD (so-called "atypical AD") do not follow the typical
      amnestic pattern and include non-amnestic focal cortical syndromes, such as
      posterior cortical atrophy and frontal variant AD. These variants exhibit
      characteristic histological lesions of Alzheimer pathology at post-mortem exam.
      By using physiopathological markers, such as cerebrospinal fluid markers, it is
      now possible to establish in vivo a biological diagnosis of AD in these focal
      cortical syndromes. We report a series of eight patients who were diagnosed with
      behavioural variant frontotemporal dementia based on their clinical,
      neuropsychological and neuroimaging findings, while CSF biomarkers showed an AD
      biological profile, thus supporting a diagnosis of frontal variant of AD.

PMID- 29213823
TI  - Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in
      frontotemporal dementia (FTD) and Alzheimer's disease (AD).
AB  - : Behavioural disturbances in frontotemporal dementia (FTD) are thought to
      reflect mainly atrophy of cortical regions. Recent studies suggest that
      subcortical brain regions, in particular the striatum, are also significantly
      affected and this pathology might play a role in the generation of behavioural
      symptoms. OBJECTIVE: To investigate prefrontal cortical and striatal atrophy
      contributions to behavioural symptoms in FTD. METHODS: One hundred and eighty-two
      participants (87 FTD patients, 39 AD patients and 56 controls) were included.
      Behavioural profiles were established using the Cambridge Behavioural Inventory
      Revised (CBI-R) and Frontal System Behaviour Scale (FrSBe). Atrophy in prefrontal
      (VMPFC, DLPFC) and striatal (caudate, putamen) regions was established via a 5
      point visual rating scale of the MRI scans. Behavioural scores were correlated
      with atrophy rating scores. RESULTS: Behavioural and atrophy ratings demonstrated
      that patients were significantly impaired compared to controls, with bvFTD being
      most severely affected. Behavioural-anatomical correlations revealed that VMPFC
      atrophy was closely related to abnormal behaviour and motivation disturbances.
      Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By
      contrast, disturbance of eating was found to be related to striatal atrophy only.
      CONCLUSION: Frontal and striatal atrophy contributed to the behavioural
      disturbances seen in FTD, with some behaviours related to frontal, striatal or
      combined fronto-striatal pathology. Consideration of striatal contributions to
      the generation of behavioural disturbances should be taken into account when
      assessing patients with potential FTD.

PMID- 29213824
TI  - A tale of two hemispheres: contrasting socioemotional dysfunction in right-
      versus left-lateralised semantic dementia.
AB  - OBJECTIVE: Semantic dementia, a subtype of frontotemporal lobar degeneration, is
      characterised by cross-modal loss of conceptual knowledge attributable to
      progressive degeneration of the left anterior temporal lobe. Much less is known
      regarding the clinical presentation of SD patients with predominantly right
      lateralised atrophy. Recent reports emphasise marked socioemotional and
      behavioural disturbances in such cases. Given the importance of the right
      anterior temporal lobes in social cognition, we hypothesised that socioemotional
      functioning would be disproportionately affected in right versus left-lateralised
      SD cases. METHODS: We assessed well-characterised cases of predominantly right
      (n=10) and left (n=12) SD and 20 matched healthy controls on tests of emotion
      processing and interpersonal functioning. RESULTS: Right SD cases showed
      disproportionate difficulties in the recognition of positive and negative facial
      emotions, specifically happiness and anger, compared with left SD cases. Deficits
      in anger recognition persisted in right SD despite covarying for facial and
      semantic processing. On a contextually rich task of emotion recognition using
      multimodal videos, no subgroup differences were evident. Finally, empathic
      concern was rated as significantly lower by caregivers of right versus left SD
      cases. Overall, the extent of socioemotional disturbance was associated with the
      degree of behavioural changes in SD. CONCLUSION: Our results reveal considerable
      overlap in the extent to which socioemotional processes are disrupted in left and
      right-lateralised cases of SD. Notably, however, right SD cases show
      disproportionate deficits for recognition of facial emotions and the capacity for
      empathic concern, supporting a specialised role for the right anterior temporal
      lobes in mediating these cognitive functions.

PMID- 29213825
TI  - Functional profile of patients with behavioral variant frontotemporal dementia
      (bvFTD) compared to patients with Alzheimer's disease and normal controls.
AB  - : There are few studies describing the functional changes in behavioral variant
      frontotemporal dementia (bvFTD) and it is not clear which aspects of
      functionality are affected by the disease. OBJECTIVE: The aim of the present
      investigation was to characterize the functional profile of patients previously
      diagnosed with bvFTD. METHODS: The sample consisted of 31 patients diagnosed with
      bvFTD, who were compared to patients with Alzheimer's disease (AD) (n=31) and to
      healthy control subjects (NC) (n=34), matched for schooling and age. bvFTD and AD
      patients were matched by severity of dementia. The protocol included the Mini
      Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Direct
      Assessment of Functional Status (DAFS-BR), Functional Activities Questionnaire
      (PFAQ), Disability Assessment for Dementia (DAD) and the Clinical Dementia Rating
      scale (CDR). RESULTS: The group with bvFTD showed worse performance on Initiation
      and Planning/Organization in the DAD and on ability to feed oneself in the DAFS
      BR, as well as higher scores on the PFAQ, suggesting greater dependence in the
      bvFTD group. CONCLUSION: The results suggest that individuals with bvFTD display
      greater functional impairment compared to AD patients with a similar degree of
      dementia severity and to healthy controls. Direct assessment of functionality
      proved unable to clearly differentiate between the dementia subtypes.

PMID- 29213826
TI  - Cultural differences are reflected in variables associated with carer burden in
      FTD: a comparison study between India and Australia.
AB  - : There is great need to understand variables behind carer burden, especially in
      FTD. Carer burden is a complex construct, and its factors are likely to vary
      depending on the type of dementia, carer characteristics and cultural background.
      OBJECTIVE: The present study aimed to compare profiles and severity of carer
      burden, depression, anxiety and stress in carers of FTD patients in India in
      comparison to Australia; to investigate which carer variables are associated with
      carer burden in each country. METHODS: Data of 138 participants (69 dyads of
      carers-patients) from India and Australia (India, n=31; Australia, n=38). Carer
      burden was assessed with the short Zarit Burden Inventory; carer depression,
      anxiety and stress were measured with the Depression, Anxiety and Stress-21.
      Dementia severity was determined with the Frontotemporal Dementia Rating Scale
      (FTD-FRS), and a range of demographic variables regarding the carer and patient
      were also obtained. RESULTS: Overall, levels of carer burden were not
      significantly different across India and Australia, despite more hours delivering
      care and higher dementia severity in India. Variables associated with burden,
      however, differed between countries, with carer depression, anxiety and stress
      strongly associated with burden in India. By contrast, depression, stress, and
      dementia severity were associated with burden in Australia. CONCLUSION: This
      study demonstrated that variables associated with carer burden in FTD differ
      between cultures. Consequently, cultural considerations should be taken into
      account when planning for interventions to reduce burden. This study suggests
      that addressing carers' skills and coping mechanisms are likely to result in more
      efficacious outcomes than targeting patient symptoms alone.

PMID- 29213827
TI  - Primary progressive aphasia: classification of variants in 100 consecutive
      Brazilian cases.
AB  - : Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome
      characterized primarily by progressive language impairment. Recently, consensus
      diagnostic criteria were published for the diagnosis and classification of
      variants of PPA. The currently recognized variants are nonfluent/agrammatic (PPA
      G), logopenic (PPA-L) and semantic (PPA-S). OBJECTIVE: To analyze the demographic
      data and the clinical classification of 100 PPA cases. METHODS: Data from 100 PPA
      patients who were consecutively evaluated between 1999 and 2012 were analyzed.
      The patients underwent neurological, cognitive and language evaluation. The cases
      were classified according to the proposed variants, using predominantly the
      guidelines proposed in the consensus diagnostic criteria from 2011. RESULTS: The
      sample consisted of 57 women and 43 men, aged at onset 67.2+/-8.1 years (range of
      between 53 and 83 years). Thirty-five patients presented PPA-S, 29 PPA-G and 16
      PPA-L. It was not possible to classify 20% of the cases into any one of the
      proposed variants. CONCLUSION: It was possible to classify 80% of the sample into
      one of the three PPA variants proposed. Perhaps the consensus classification
      requires some adjustments to accommodate cases that do not fit into any of the
      variants and to avoid overlap where cases fit more than one variant. Nonetheless,
      the established current guidelines are a useful tool to address the
      classification and diagnosis of PPA and are also of great value in standardizing
      terminologies to improve consistency across studies from different research
      centers.

PMID- 29213828
TI  - Nonpharmacological interventions for cognitive impairments following primary
      progressive aphasia: a systematic review of the literature.
AB  - : This study provided a systematic review on nonpharmacological interventions
      applied to patients diagnosed with Primary Progressive Aphasia (PPA) and its
      variants: Semantic (SPPA), Nonfluent (NFPPA) and Logopenic (LPPA) to establish
      evidence-based recommendations for the clinical practice of cognitive
      rehabilitation for these patients. METHODS: A PubMed and LILACS literature search
      with no time restriction was conducted with the keywords PPA (and its variants)
      AND rehabilitation OR training OR intervention OR therapy OR treatment OR
      effectiveness. To develop its evidence-based recommendations, a research
      committee identified questions to be addressed and determined the level of
      evidence for each study according to published criteria (Cicerone et al., 2000).
      Overall evidence for treatments was summarized and recommendations were derived.
      RESULTS: Our search retrieved articles published from 1995 to 2013: 21 for SPPA,
      8 for NFPPA, 3 for LPPA and 8 for PPA with no specification. Thirty-five studies
      were rated as Class III, consisting of studies with results obtained from one or
      more single-cases and that used appropriate single-subject methods with adequate
      quantification and analysis of results. The level of evidence of three functional
      interventions could not be established. One study was rated as Class II and
      consisted of a nonrandomized case-control investigation. CONCLUSION: Positive
      results were reported in all reviewed studies. However, in order to be
      recommended, some investigation regarding the intervention efficacy was required.
      Results of the present review allows for recommendation of some
      nonpharmacological interventions for cognitive deficits following PPA as Practice
      Options. Suggestions for further studies on PPA interventions and future research
      are discussed.

PMID- 29213829
TI  - Prefrontal damage in childhood and changes in the development of personality: a
      case report.
AB  - Frontal lobe lesions are associated with behavioral abnormalities and executive
      dysfunction. When these lesions occur early in life, the symptoms are even more
      severe as the anatomical and functional substrates underlying personality and
      behavior are damaged, distorting normal modulation by interaction with the
      psychosocial environment. We present a case of a 40-year-old man who suffered a
      frontal lobe lesion at the age of nine years and developed impulsivity,
      disinhibition and inappropriate behaviors while showing some preservation of
      insight. Brain MRI revealed lesions to bilateral orbitofrontal cortex,
      ventromedial prefrontal cortex, anterior cingulate gyri and genu of the corpus
      callosum, which were more extensive on the right side. The right prefrontal
      dorsolateral cortex was severely damaged, whereas the right ventrolateral
      prefrontal cortex was spared. We will discuss the correlation of the damaged pre
      frontal regions with the symptoms presented by the patient.

PMID- 29213831
TI  - In the June 2013 issue.

PMID- 29213830
TI  - Very late-onset behavioral variant frontotemporal dementia.
AB  - Current concepts regarding frontotemporal lobar degeneration (FTLD) have evolved
      rapidly in recent years. Genetically determined FTLD cohorts have broadened our
      knowledge pertaining to its clinical presentation, neuroimaging findings and
      demographics. In this study we present a case report of a patient diagnosed with
      behavioral variant frontotemporal dementia diagnosis in her nineties during
      hospital admission for a ground-level fall. We believe this case reinforces the
      pervasive nature of this clinical entity, and may contribute to an increased
      awareness of this diagnostic possibility in late-onset dementia.

PMID- 29213832
TI  - Enhancement of carer skills and patient function in the non-pharmacological
      management of frontotemporal dementia (FTD): A call for randomised controlled
      studies.
AB  - FTD is a unique condition which manifests with a range of behavioural symptoms,
      marked dysfunction in activities of daily living (ADL) and increased levels of
      carer burden as compared to carers of other dementias. No efficacious
      pharmacological interventions to treat FTD currently exist, and research on
      pharmacological symptom management is variable. The few studies on non
      pharmacological interventions in FTD focus on either the carer or the patients'
      symptoms, and lack methodological rigour. This paper reviews and discusses
      current studies utilising non-pharmacological approaches, exposing the clear need
      for more rigorous methodologies to be applied in this field. Finally, a
      successful randomised controlled trial helped reduce behaviours of concern in
      dementia, and through implementing participation in tailored activities, the FTD
      specific Tailored Activities Program (TAP) is presented. Crucially, this protocol
      has scope to target both the person with FTD and their carer. This paper
      highlights that studies in this area would help to elucidate the potential for
      using activities to reduce characteristic behaviours in FTD, improving quality of
      life and the caregiving experience in FTD.

PMID- 29213833
TI  - Basal ganglia calcification as a putative cause for cognitive decline.
AB  - Basal ganglia calcifications (BGC) may be present in various medical conditions,
      such as infections, metabolic, psychiatric and neurological diseases, associated
      with different etiologies and clinical outcomes, including parkinsonism,
      psychosis, mood swings and dementia. A literature review was performed
      highlighting the main neuropsychological findings of BGC, with particular
      attention to clinical reports of cognitive decline. Neuroimaging studies combined
      with neuropsychological analysis show that some patients have shown progressive
      disturbances of selective attention, declarative memory and verbal perseveration.
      Therefore, the calcification process might represent a putative cause for
      dementia syndromes, suggesting a probable link among calcinosis, the aging
      process and eventually with neuronal death. The increasing number of reports
      available will foster a necessary discussion about cerebral calcinosis and its
      role in determining symptomatology in dementia patients.

PMID- 29213834
TI  - Studies on semantic priming effects in right hemisphere stroke: A systematic
      review.
AB  - : The role of the right cerebral hemisphere (RH) associated with semantic priming
      effects (SPEs) must be better understood, since the consequences of RH damage on
      SPE are not yet well established. OBJECTIVE: The aim of this article was to
      investigate studies analyzing SPEs in patients affected by stroke in the RH
      through a systematic review, verifying whether there are deficits in SPEs, and
      whether performance varies depending on the type of semantic processing evaluated
      or stimulus in the task. METHODS: A search was conducted on the LILACS, PUBMED
      and PSYCINFO databases. RESULTS: Out of the initial 27 studies identified, 11
      remained in the review. Difficulties in SPEs were shown in five studies.
      Performance does not seem to vary depending on the type of processing, but on the
      type of stimulus used. CONCLUSION: This ability should be evaluated in
      individuals that have suffered a stroke in the RH in order to provide treatments
      that will contribute to their recovery.

PMID- 29213835
TI  - Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal
      for a Brazilian version of the Short Battery for Severe Impairment (SIB-8).
AB  - : The measurement of cognitive abilities of patients with severe dementia can
      serve a wide range of methodological and clinical needs. OBJECTIVE: To validate a
      proposed severe impairment battery SIB-8 for a Brazilian population sample as
      part of the neuropsychological assessment of patients with Alzheimer's disease
      (AD) in advanced stages. METHODS: After a systematic process of translation and
      back-translation, the SIB-8 was applied to 95 patients with AD at different
      stages; moderate, moderately severe and severe according to FAST subdivisions (5,
      6 and 7), with scores on the Mini-Mental State Examination (MMSE) of between 5
      and 15 and followed by the Division of Behavioral Neurology and the Center for
      Aging Brain of the Federal University of Sao Paulo - UNIFESP. RESULTS:
      Inferential data revealed that the SIB-8 instrument behaved differently at each
      stage of the disease with a statistical value of sensitivity p<0.001, gradually
      reflecting the expected course of the dementia, inherent with the decline of
      cognitive functions. CONCLUSION: Findings indicated that the SIB-8 is a useful
      tool for the evaluation and prospective comparison of AD patients in advanced
      stages, retaining its original characteristics in our population.

PMID- 29213836
TI  - Neuropsychiatric symptoms and severity of dementia.
AB  - : Neuropsychiatric symptoms (NPS) cause distress, disabilitiy and reduced quality
      of life for both the patient and their families. OBJECTIVE: To evaluate the
      prevalence of NPS as a specific stage of dementia status. METHODS: A cross
      sectional study in patients attending an outpatient clinic for dementia was
      performed. We applied the Neuropsychiatric Inventory and Clinical Dementia Rating
      (CDR) scale. Statistical analysis was carried out with SPSS 17 software. RESULTS:
      The 124 subjects (mean age of 80.4+/-7.0 years), 88 women (70.9%) had average
      duration of dementia of 7.1+/-3.2 years, most common dementias of Alzheimer's
      disease (35.5%) and mixed (31.5%) and most prevalent NPS of apathy (75%) and
      irritability (66.9%). Correlation between apathy and a CDR 1 had a PR (prevalence
      ratio) = 0.289 and p<0.001while between apathy and CDR 4-5 (PR=8.333, p<0.005). A
      similar result was found between aberrant motor behavior (AMB) and CDR 1
      (PR=0.352, p<0.003) and between AMB and CDR4-5 (PR=2.929, p<0.006). CONCLUSION:
      Alzheimer's disease and mixed dementia were predominant, while apathy and AMB
      were detected in association with the progressive stages of dementia.

PMID- 29213837
TI  - Senile dementia and pharmacological drugs.
AB  - : Side effects and drug interactions are common in the elderly and highly
      relevant in the demented, being routinely confused with symptoms of cognitive
      impairment. Which drugs are most consumed by this patient group? Do prescription
      patterns differ between the demented and non-demented? OBJECTIVE: To define drug
      consumption quantitatively and qualitatively in demented (D) and non-demented
      (ND) elderly. METHODS: Patients were divided into men and women, by age group
      (<80 and >=80 years), non-demented and demented status, and consumers of <=3 or
      >3 drugs. As a criterion comparing groups, the Chi-square (Fisher's exact) test
      was employed. This study is part of Project No. 405/10 approved by the Ethics
      Committee of the institution. RESULTS: The sample had a mean age of 81.5+/-8.8
      years, 29 D (21 women and 8 men) and 21 ND (16 women and 5 men), 12 consumers of
      up to three drugs (7 D and 5 ND) and 38 consumers of 3 medications or more (22 D
      and 16 ND). The most used drugs among dementia patients were aspirin, angiotensin
      converting enzyme inhibitors, statins, selective serotonin reuptake inhibitors,
      and vitamins. Drugs most consumed by non-demented included vitamins, aspirin,
      calcium carbonate, proton pump inhibitors, statins and alendronate sodium. There
      was no statistical significance on any of the comparisons, although the number of
      elderly consumers of vitamins in the ND had a p-value of 0.06 (Yates).
      CONCLUSION: The elderly in this series, regardless of dementia status, gender or
      age group, had similar drug consumption patterns and used multiple drugs
      simultaneously.

PMID- 29213838
TI  - Education, leisure activities and cognitive and functional ability of Alzheimer's
      disease patients: A follow-up study.
AB  - : Education and participation in leisure activities appear to be highly relevant
      variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive
      Reserve construct. OBJECTIVE: [A] To determine the association between education,
      cognitive and functional ability of AD patients; [B] To determine the association
      between participation in leisure activities and cognitive and functional ability
      of AD patients; [C] To evaluate the association of education and participation in
      leisure activities in the course of AD. METHODS: Functional and
      neuropsychological abilities of 120 outpatients with probable AD were evaluated
      at baseline, at 36 and 54 months. Data collected at baseline included socio
      demographics, clinical variables, education and frequency of participation in
      leisure activities throughout life. All participants and/or caregivers answered
      the questionnaire, "Participation in leisure activities throughout life" while
      patients completed the MMSE, the Clinical Dementia Rating scale,
      neuropsychological tests from the Lisbon Screening for Dementia Assessment,
      Barthel Index and Lawton and Brody's Index. RESULTS: AD patients with higher
      levels of education achieved better results on cognitive tests. The participants
      with higher participation in leisure activities exhibited better results on
      cognitive and functional tests than those with lower participation. The disease
      progression was linear and progressed similarly regardless of the level of
      education of participants. However, the results suggest a slower disease
      progression in patients with a higher level of participation in leisure
      activities throughout their lives. CONCLUSION: AD patients with high education
      and high participation in leisure activities may benefit from a slower cognitive
      and functional decline after diagnosis of AD.

PMID- 29213839
TI  - Good rate of clinical response to cholinesterase inhibitors in mild and moderate
      Alzheimer's disease after three months of treatment: An open-label study.
AB  - : Life expectancy in Brazil has increased markedly over the last 30 years. Hence,
      age-related disorders, such as Alzheimer's disease (AD), warrant special
      attention due to their high prevalence in the elderly. Pharmacologic treatment of
      AD is based on cholinesterase inhibitors (ChEI) and memantine, leading to modest
      clinical benefits both in the short and long-term. However, clinical response is
      heterogeneous and needs further investigation. OBJECTIVE: To investigate the rate
      of response to ChEI in AD after three months of treatment. METHODS: Patients with
      mild or moderate dementia due to probable AD or to AD associated with
      cerebrovascular disease were included in the study. The subjects were assessed at
      baseline and again after three months of ChEI treatment. Subjects were submitted
      to the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale, Katz
      Basic Activities of Daily Living, Pfeffer Functional Activities Questionnaire,
      Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Good
      response was defined by a gain of >=2 points on the MMSE after three months of
      treatment in relation to baseline. RESULTS: Seventy-one patients, 66 (93%) with
      probable AD and five (7%) with AD associated with cerebrovascular disease, were
      evaluated. The good response rate at three months was 31.0%, being 37.2% and
      21.4% in mild and moderate dementia, respectively. There were no significant
      differences on most tests, except for improvement in hallucinations, agitation
      and dysphoria in moderate dementia patients. CONCLUSION: The rate of good
      clinical response to ChEI was higher than usually reported. Specific behavioral
      features significantly improved in the subgroup of moderate dementia.

PMID- 29213840
TI  - Cognitive anosognosia and behavioral changes in probable Alzheimer's disease
      patients.
AB  - : Anosognosia, impairment insight and unawareness of deficits are used as
      equivalent terms in this study. OBJECTIVE: To investigate the relationship
      between the presence of anosognosia symptoms and cognitive domains, functional
      abilities, and neuropsychiatric symptoms in patients with probable Alzheimer's
      disease (pAD) and elderly controls (EC). METHODS: Twenty-one pAD (14 women) and
      twenty-two EC (16 women) were submitted to a neuropsychological battery of tests
      assessing global cognitive status, and specific cognitive functions: memory,
      executive and attention functions, verbal fluency and visuoconstructive
      abilities. Additionally, functional abilities (FAQ) and neuropsychiatric symptoms
      (NPI) were measured. RESULTS: The linear regression statistical test found
      general anosognosia to be associated with subjective memory complaints, age and
      Arithmetic-DRS in the EC group. On the other hand, cognitive and functional
      abilities scores (Arithmetic-DRS, IQCODE and FAQ) were the best predictors in pAD
      patients, particularly for behavioral awareness. CONCLUSION: These results
      indicated that different variables are associated with self-awareness for pAD
      patients and EC, but for both groups executive functions appear to play an
      important role, contributing particularly to awareness of behavioral changes.

PMID- 29213841
TI  - Cognitive assessment in an elderly population with metabolic syndrome in Brazil.
AB  - : Chronic degenerative conditions are very common in the elderly. According to
      medical literature, there is a correlation between cognitive impairment among
      elders and arterial hypertension/hyperglycemia which in turn are common diseases
      among the elderly population worldwide. Nonetheless, data on the association
      between cognitive impairment and Metabolic Syndrome (MetS) remains controversial.
      OBJECTIVE: To compare the cognitive status of Brazilian elderly outpatients with
      and without MetS. METHODS: A cross-sectional case-control study with 49 subjects
      (25 MetS and 24 controls) who underwent a global geriatric and neuropsychological
      assessment was carried out. The scores for cognitive abilities (sustained
      attention, alternating attention, immediate memory, working memory, memory -
      immediate recall, memory - delayed recall, memory - recognition, executive
      function, ideomotor praxis, constructive praxis, naming ability, verbal fluency)
      were compared with the data for the normal population and differences between
      case and control groups were analyzed using Student's t-test or the Mann-Whitney
      test. RESULTS: Forty-five patients (91.8%) were female, with a mean age of 73.9+/
      5.9 years, and 3.0+/-1.0 years of schooling. A significant difference (p<0.01)
      was found between case and control groups regarding the MetS components. For
      cognitive abilities, no statistically significant difference was detected between
      the groups and all subjects presented low cognitive scores. CONCLUSION: The
      results obtained in the present study showed that MetS was not associated with
      cognitive impairment in this population. Further prospective studies are
      necessary to investigate the influence of well-controlled MetS on cognitive
      performance among elders.

PMID- 29213842
TI  - Prevalence of brain calcifications in a Brazilian cohort: A retrospective study
      in radiology services.
AB  - : Brain calcifications may be present in a wide range of neuropsychiatric,
      infectious traumatic, neoplastic and endocrine conditions, associated with motor
      and cognitive symptoms. They are often considered "physiologic" or pathologic.
      OBJECTIVE: To determine the prevalence of brain calcifications in a Brazilian
      cohort. METHODS: 1898 consecutive patients underwent skull CTs, comprising 836
      men and 1062 women. RESULTS: Among all 1898 patients, 333 (197 women and 136 men)
      presented with brain calcifications, representing an overall prevalence of
      17.54%. The prevalence in the female group was 18.54% versus 16.26% in the male
      group. CONCLUSIONS: A growth in incidental findings on CT scans are likely as
      these exams become more widely available. However, a current debate between
      radiologists and regulators is set to redefine the CT usage, especially in the
      United States and the United Kingdom, considering new norms for use and radiation
      dosage per exam.

PMID- 29213843
TI  - Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T.
AB  - : Proton magnetic resonance spectroscopy (MRS) of the human brain has proven to
      be a useful technique in several neurological and psychiatric disorders and
      benefits from higher field scanners as signal intensity and spectral resolution
      are proportional to the magnetic field strength. OBJECTIVE: To investigate the
      effects of the magnetic field on the measurement of brain metabolites in a
      typical routine clinical setting. METHODS: Single voxel spectra were acquired
      from the posterior cingulate cortex in 26 healthy subjects. Each subject was
      scanned consecutively at 1.5T and 3.0T in a randomly distributed order. RESULTS:
      SNR and peak width improvements were observed at higher fields. However, SNR
      improvement was lower than the theoretical two-fold improvement. Other than the
      values obtained for creatine (Cre) and myo-Inositol (mI), which were both higher
      at 3.0T, all metabolite concentrations obtained were roughly the same at both
      field strengths. All the metabolite concentrations were estimated with a Cramer
      Rao lower bounds (CRLB) lower than 15% of the calculated concentrations.
      CONCLUSIONS: Even though the present study supports the expected benefits of
      higher field strength for MRS, there are several factors that can lead to
      different quantitative results when comparing 1.5T to 3.0T MRS. Future
      comparative studies are necessary to refine the metabolite thresholds for early
      detection and quantification of distinct neurological and psychiatric disorders
      using 3.0T MRS.

PMID- 29213844
TI  - In the September 2013 issue.

PMID- 29213845
TI  - Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical
      review with a focus on neuroimaging.
AB  - The objective of this critical review of the literature was to reveal the neural
      circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in
      Alzheimer's disease (AD) patients through the association of these symptoms with
      neuroimaging findings. The search for articles was performed on PUBMED from
      January 2000 to May 2013, using the key words: Dementia AND BPSD; Dementia AND
      Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations,
      Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability,
      Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were
      reviewed and important contributions, especially regarding the psychopathological
      concepts discussed, were also considered even if not included in this time
      period. The available evidence suggests the three most relevant neurobiological
      models for neuropsychiatric symptoms in Alzheimer's disease are the frontal
      subcortical circuits, the cortico-cortical networks, and the monoaminergic
      system. We discussed the association of the individual symptoms or syndromes with
      these models.

PMID- 29213846
TI  - Assessment of neuropsychiatric symptoms in dementia: toward improving accuracy.
AB  - The issue of this article concerned the discussion about tools frequently used
      tools for assessing neuropsychiatric symptoms of patients with dementia,
      particularly Alzheimer's disease. The aims were to discuss the main tools for
      evaluating behavioral disturbances, and particularly the accuracy of the
      Neuropsychiatric Inventory - Clinician Rating Scale (NPI-C). The clinical
      approach to and diagnosis of neuropsychiatric syndromes in dementia require
      suitable accuracy. Advances in the recognition and early accurate diagnosis of
      psychopathological symptoms help guide appropriate pharmacological and non
      pharmacological interventions. In addition, recommended standardized and
      validated measurements contribute to both scientific research and clinical
      practice. Emotional distress, caregiver burden, and cognitive impairment often
      experienced by elderly caregivers, may affect the quality of caregiver reports.
      The clinician rating approach helps attenuate these misinterpretations. In this
      scenario, the NPI-C is a promising and versatile tool for assessing
      neuropsychiatric syndromes in dementia, offering good accuracy and high
      reliability, mainly based on the diagnostic impression of the clinician. This
      tool can provide both strategies: a comprehensive assessment of neuropsychiatric
      symptoms in dementia or the investigation of specific psychopathological
      syndromes such as agitation, depression, anxiety, apathy, sleep disorders, and
      aberrant motor disorders, among others.

PMID- 29213848
TI  - Correlation between neuropsychiatric symptoms and caregiver burden in a
      population-based sample from Sao Paulo, Brazil: a preliminary report.
AB  - : Neuropsychiatric symptoms and caregiver burden are highly prevalent in older
      adults with Alzheimer's disease (AD).OBJECTIVE: To evaluate the correlation
      between neuropsychiatric symptoms and caregiver burden in a community-based
      sample from Sao Paulo, Brazil. METHODS: A total of 1,563 randomly-selected
      subjects were assessed by the Mini-Mental State Examination, Fuld Object Memory
      Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly and Bayer
      - Activities of Daily Living Scale. Subjects considered screen-positives were
      submitted to a dementia workup and diagnosis was determined according to ICD-10
      criteria. The neuropsychiatric Inventory was applied to caregivers to evaluate
      neuropsychiatric symptoms and the Zarit Burden Interview was also applied to
      assess caregivers' burden. RESULTS: Sixty-one AD patients, 25 Cognitively
      Impaired Non Demented (CIND) and 79 healthy elderly subjects were evaluated.
      Zarit mean scores for controls, CIND and AD were 2.32, 3.92 and 20.11,
      respectively. There was strong positive correlation between total NPI and Zarit
      scores. CONCLUSION: In conclusion, neuropsychiatric symptoms showed a significant
      association with higher rates of caregiver stress.

PMID- 29213847
TI  - Prevalence of depressive symptoms among elderly in the city of Tremembe, Brazil:
      preliminary findings of an epidemiological study.
AB  - : Depression is a heterogeneous mental disease classified as a set of disorders,
      which manifest with a certain duration, frequency and intensity. The prevalence
      of depression in the elderly ranges from 0.5 to 16%. OBJECTIVE: To establish, in
      an epidemiological study, the prevalence of significant depressive symptoms in
      the population aged 60 years or older. METHODS: Results of a cross-sectional
      epidemiological study, involving home visits, being carried out in the city of
      Tremembe, Brazil, were reported. The sample was randomly selected by drawing 20%
      of the population over 60 years from each of the city's census sectors. In this
      single-phase study, the assessment included clinical history, physical and
      neurological examination, cognitive evaluation, the Cornell scale and the Patient
      Health Questionnaire for psychiatric symptoms. Scores greater than or equal to 8
      on the Cornell scale were taken to indicate the presence of depressive symptoms.
      RESULTS: A total of 455 elders were assessed, and of these 169 (37.1%) had
      clinically significant depressive symptoms (CSDS). Depression prevalence was
      higher among women (p<0.001) and individuals with lower education (p=0.033). The
      Chi-square test for trends showed a significant relationship where lower
      socioeconomic status was associated with greater likelihood of depressive
      symptoms (p=0.005). CONCLUSION: The prevalence of depressive symptoms was high in
      this sample of the population-based study and was associated with female gender,
      low educational level and socioeconomic status. The assessment of the entire
      population sample must be completed.

PMID- 29213849
TI  - Neuropsychiatric Symptoms (NPS) in patients with pure Vascular Dementia (VaD) and
      Mixed Dementia (MD) from a memory outpatient clinic in southeast Brazil.
AB  - : Vascular Dementia (VaD) and Vascular Cognitive Impairment (VCI) are
      increasingly common worldwide. Nevertheless, the clinical-neuropsychiatric
      profile of these patients at presentation is still poorly characterized in
      developing countries. OBJECTIVE: We aimed to characterize the prevalence of
      neuropsychiatric symptoms, as well as the clinical and cognitive profile of
      patients with VaD and VCI in our tertiary University outpatient cognitive clinic.
      METHODS: We reviewed data on 253 patients diagnosed with VaD or VCI at our center
      between January 1996 and December 2005, located in an industrial region of the
      state of Sao Paulo, southeast Brazil. We excluded 19 patients who did not
      complete the medical investigation or who did not meet the clinical or
      neuroimaging criteria for vascular dementia. We collected socio-demographic data,
      educational level, vascular risk factors, behavioral and neuropsychological
      symptoms and cognitive complaints at presentation. RESULTS: Two hundred and
      thirty-four cases were included in this analysis. The mean age was 67.77+/-10.35
      years; 72% were males and 82% had less than four years of education (average
      2.84+/-2.96 years). The initial Clinical Dementia Rating score was 2 & 3 in 68%.
      A total of 185 patients had neuropsychiatric symptoms distributed in main
      categories as follows: psychosis (52.6%), hallucinations (23.5%), psychomotor
      agitation (22.5%), depression (17.5%) and apathy (17.5%). Hypertension and
      previous stroke were the most prevalent risk factors. CONCLUSION: We found a high
      prevalence of neuropsychiatric symptoms. The clinical-neuropsychiatric profile of
      patients presenting to cognitive clinics in developing countries may differ
      greatly to that of more developed nations. These characteristics may have
      implications for public health strategies.

PMID- 29213850
TI  - BPSD following traumatic brain injury.
AB  - : Annually, 700,000 people are hospitalized with brain injury acquired after
      traumatic brain injury (TBI) in Brazil. OBJECTIVE: We aim to review the basic
      concepts related to TBI, and the most common Behavioral and Psychological
      Symptoms of Dementia (BPSD) findings in moderate and severe TBI survivors. We
      also discussed our strategies used to manage such patients in the post-acute
      period. METHODS: Fifteen TBI outpatients followed at the Center for Cognitive
      Rehabilitation Post-TBI of the Clinicas Hospital of the University of Sao Paulo
      were submitted to a neurological, neuropsychological, speech and occupational
      therapy evaluation, including the Mini-Mental State Examination. Rehabilitation
      strategies will then be developed, together with the interdisciplinary team, for
      each patient individually. Where necessary, the pharmacological approach will be
      adopted. RESULTS: Our study will discuss options of pharmacologic treatment
      choices for cognitive, behavioral, or affective disorders following TBI,
      providing relevant information related to a structured cognitive rehabilitation
      service and certainly will offer an alternative for patients and families
      afflicted by TBI. CONCLUSION: Traumatic brain injury can cause a variety of
      potentially disabling psychiatric symptoms and syndromes. Combined behavioral and
      pharmacological strategies, in the treatment of a set of highly challenging
      behavioral problems, appears to be essential for good patient recovery.

PMID- 29213851
TI  - French version of the Rating Scale for aggressive behaviour in the Elderly (F
      RAGE): psychometric properties and diagnostic accuracy.
AB  - : Aggressive behaviour is the most disturbing and distressing behaviour displayed
      by elderly people. The prevalence of aggressive behaviour is around 50% among
      psychogeriatric patients. OBJECTIVE: This study sought to analyze the
      psychometric properties and diagnostic accuracy of the French version of the
      Rating Scale for Aggressive Behaviour in the Elderly (F-RAGE). METHODS: The F
      RAGE was administered to 79 patients hospitalized in a geriatric psychiatry
      department. A psychiatrist, who was blind to the subjects' RAGE scores, performed
      the diagnosis for aggressivity based on global clinical impression. The F-RAGE
      and MMSE were applied by a trained researcher blind to subjects' clinical
      diagnoses while the Cohen-Mansfield Agitation Inventory and Neuropsychiatric
      Inventory were administered by medical and nursing staff. Internal consistency,
      reliability, cut-off points, sensitivity and specificity for F-RAGE were
      estimated. RESULTS: F-RAGE showed satisfactory validity and reliability
      measurements. Regarding reliability, Cronbach's alpha coefficient was
      satisfactory with a value of 0.758. For diagnostic accuracy, a cut-off point of 8
      points (sensitivity=74.19%; specificity=97.98%) and area under curve of 0.960
      were estimated to distinguish between aggressive patients and control subjects.
      DISCUSSION: F-RAGE showed acceptable psychometric properties, supported by
      evidence of validity and reliability for its use in the diagnosis of aggressive
      behaviour in elderly.

PMID- 29213852
TI  - The association between caregiver distress and individual neuropsychiatric
      symptoms of dementia.
AB  - : Neuropsychiatric symptoms (NPS) of dementia constitute one of the most related
      factors to caregiver burden and patients' early institutionalization. Few studies
      in Brazil have examined which symptoms are associated with higher levels of
      caregiver distress. OBJECTIVE: To evaluate the caregiver distress related to
      individual NPS in familial caregivers of patients with dementia. We also examined
      which caregiver and patient factors predict caregiver distress associated with
      NPS. METHODS: One hundred and fifty-nine familial caregiver and dementia
      outpatient dyads were included. The majority of the patients had a diagnosis of
      Alzheimer's disease (66.7%). Caregivers were assessed with a sociodemographic
      questionnaire, Beck Anxiety and Depression Inventories, and the Neuropsychiatric
      Inventory - Distress Scale. Patients were submitted to the Mini-Mental State
      Examination, Functional Activities Questionnaire, and the Neuropsychiatric
      Inventory. Spearman's rank correlation was used to assess the relationships
      between the continuous variables. Multiple linear regression analyses with
      backward stepping were performed to assess the ability of caregiver and patient
      characteristics to predict levels of caregiver distress associated with NPS.
      RESULTS: Apathy (M=1.9; SD=1.8), agitation (M=1.3; SD=1.8), and aberrant motor
      behavior (AMB) (M=1.2; SD=1.7) were the most distressful NPS. The
      frequency/severity of NPS was the strongest factor associated with caregiver
      distress (rho=0.72; p<0.05). CONCLUSION: The early recognition and management of
      apathy, agitation and AMB in dementia patients by family members and health
      professionals may lead to better care and quality of life for both patients and
      caregivers.

PMID- 29213853
TI  - Staff training to reduce behavioral and psychiatric symptoms of dementia in
      nursing home residents: a systematic review of intervention reproducibility.
AB  - Staff training has been cited as an effective intervention to reduce behavioral
      and psychiatric symptoms of dementia (BPSD) in nursing home residents. However,
      the reproducibility of interventions can be a barrier to their dissemination. A
      systematic review of controlled clinical trials on the effectiveness of staff
      training for reducing BPSD, published between 1990 and 2013 on the EMBASE,
      PUBMED, LILACS, PSYCHINFO and CINAHL databases, was carried out to evaluate the
      reproducibility of these interventions by 3 independent raters. The presence of
      sufficient description of the intervention in each trial to allow its
      reproduction elsewhere was evaluated. Descriptive analyses were carried out.
      Despite reference to a detailed procedures manual in the majority of trials,
      these manuals were not easily accessible, limiting the replication of studies.
      The professional expertise requirement for training implementation was not
      clearly described, although most studies involved trainers with moderate to
      extensive expertise, further limiting training reproducibility.

PMID- 29213854
TI  - Serum levels of soluble TNF-alpha receptors but not BDNF are associated with
      apathy symptoms in mild Alzheimer's disease and amnestic mild cognitive
      impairment.
AB  - : Apathy is intimately associated with dementia. Unfortunately, its
      pathophysiology remains poorly understood. The motivational impairment that
      characterizes this disorder might share the same inflammatory mechanisms, as
      suggested by the sickness behavior theory. OBJECTIVE: The primary aim of this
      study was to investigate the association between apathy symptoms and serum levels
      of tumor necrosis factor alpha (TNF-alpha) and its soluble receptors. Brain
      derived neurotrophic factor (BDNF) levels were also analyzed since these have
      been associated with depression, a condition which shares abulic features with
      apathy. METHODS: The sample consisted of 27 subjects with mild Alzheimer's
      disease or amnestic mild cognitive impairment, who were submitted to specific
      apathy evaluation using the Apathy Scale (AS) and provided blood samples for
      biomarker analysis. Participants were categorized into two groups according to
      median AS scores (17 points). RESULTS: Subjects with higher apathy symptoms
      (n=13) displayed higher levels of TNF-alpha soluble receptors (type 1: p=0.03;
      type 2: p=0.04). No other difference was found between groups. CONCLUSION: These
      findings point to the involvement of inflammatory mediators in the genesis of
      apathy symptoms, as suggested by the sickness behavior theory.

PMID- 29213855
TI  - Anti-NMDA-R encephalitis: follow-up of 24 months.
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is the second-most
      common cause of autoimmune encephalitis, based on epidemiological studies.It has
      been predominantly described in young females, with prominent psychiatric
      symptoms, memory loss, decrease in level of consciousness, epilepsy, and central
      hypoventilation. The condition is commonly associated with mature ovarian
      teratomas. We describe a video report with a classic presentation of anti-NMDA-R
      encephalitis in a young patient with no identifiable tumor. Anti-NMDA
      encephalitis is a recognizable and treatable illness. The prognosis of patients
      depends on early diagnosis, implementation of appropriate immunomodulatory
      therapy and, in paraneoplastic cases, complete tumor removal. Clinicians should
      be wary of this condition, especially when assessing patients with recent onset
      of psychiatric symptoms unresponsive to antipsychotic treatment.

PMID- 29213856
TI  - Depressive symptoms and cognitive deficits in a cancer patient submitted to
      chemotherapy with 5-Fluoracil: a case report.
AB  - Cognitive deficits in cancer patients can be related to depression, anxiety, and
      the side effects of treatments such as fatigue. In this case report, we described
      an elderly patient with rectal adenocarcinoma, which presented depressive
      symptoms and memory complaints after treatment with 5-Fluoracil and Leucovorin.
      Depressive symptoms improved after two months but cognitive and functional
      impairment worsened suggesting the diagnosis of mild dementia. Structural and
      functional brain changes were seen on neuroimaging exams. Rivastigmine was
      introduced up to 12 mg/day, and after a one-year follow up the patient remained
      stable. Cognitive deficits can be a consequence of cancer therapies and a
      protocol to investigate deficits cognitive could be useful to the diferential
      diagnosis and management of elderly cancer patients submitted to chemotherapy.

PMID- 29213858
TI  - In the December 2013 issue.

PMID- 29213857
TI  - Dissociation of depression from apathy in traumatic brain injury: a case report.
AB  - Although not evident clinically, lesions to the prefrontal cortex cause great
      social and functional impairment to patients. The anterior cingulate cortex is
      intimately involved with motivational behavior and after injury to this area the
      onset of an apathetic state can be observed. This paper describes the case of a
      patient with traumatic brain injury to the prefrontal lobe presenting with a
      depressive syndrome associated with apathetic symptoms. After appropriate
      treatment for depression, intense apathy was revealed, an irreversible sequelae
      of the traumatic brain injury, constituting the main barrier to the patient's
      return of lifestyle and independence.

PMID- 29213859
TI  - Epidemiology of mild cognitive impairment in Brazil.
AB  - With the worldwide increase in longevity and rising prevalence of cognitive
      disorders in the aged population, efforts have been made to characterize mild
      cognitive impairment (MCI) and its prevalence and/or incidence in a number of
      countries, given MCI may be a pre-dementia phase of degenerative conditions. The
      aim of this review was to retrieve the available data on the prevalence and
      incidence of mild cognitive impairment (MCI) in Brazil and compare these with
      rates found by studies conducted in other countries. The Pubmed and Scielo
      databases were searched using the following search terms: mild cognitive
      impairment, prevalence, incidence, including studies in both English and
      Portuguese languages. Only one study on MCI prevalence has been published in
      Brazil, reporting a prevalence rate of 6.1% and incidence of 13.2/1000 persons
      year among those aged 60 years or over. Prevalence rates for other countries are
      also reported. The prevalence and incidence of MCI found in Brazil is similar to
      rates observed in other countries.

PMID- 29213860
TI  - Reliability of cognitive tests of ELSA-Brasil, the brazilian longitudinal study
      of adult health.
AB  - : Cognitive function evaluation entails the use of neuropsychological tests,
      applied exclusively or in sequence. The results of these tests may be influenced
      by factors related to the environment, the interviewer or the interviewee.
      OBJECTIVES: We examined the test-retest reliability of some tests of the
      Brazilian version from the Consortium to Establish a Registry for Alzheimer's
      disease. METHODS: The ELSA-Brasil is a multicentre study of civil servants (35-74
      years of age) from public institutions across six Brazilian States. The same
      tests were applied, in different order of appearance, by the same trained and
      certified interviewer, with an approximate 20-day interval, to 160 adults (51%
      men, mean age 52 years). The Intraclass Correlation Coefficient (ICC) was used to
      assess the reliability of the measures; and a dispersion graph was used to
      examine the patterns of agreement between them. RESULTS: We observed higher
      retest scores in all tests as well as a shorter test completion time for the
      Trail Making Test B. ICC values for each test were as following: Word List
      Learning Test (0.56), Word Recall (0.50), Word Recognition (0.35), Phonemic
      Verbal Fluency Test (VFT, 0.61), Semantic VFT (0.53) and Trail B (0.91). The
      Bland-Altman plot showed better correlation of executive function (VFT and Trail
      B) than of memory tests. CONCLUSIONS: Better performance in retest may reflect a
      learning effect, and suggest that retest should be repeated using alternate forms
      or after longer periods. In this sample of adults with high schooling level,
      reliability was only moderate for memory tests whereas the measurement of
      executive function proved more reliable.

PMID- 29213861
TI  - Mattis dementia rating scale (DRS) normative data for the brazilian middle-age
      and elderly populations.
AB  - OBJECTIVE: To expand norms for the Mattis Dementia Rating Scale (DRS) for the
      Brazilian middle-age and elderly populations. METHODS: The DRS was administered
      to 502 individuals without cognitive deficits, 312 women and 190 men, aged 50
      years or over and with educational level ranging from 0 to 13 years or more. The
      sample was composed of subjects who participated in other studies, from Caete
      (Minas Gerais state), Ribeirao Preto (Sao Paulo state) and Sao Paulo (Sao Paulo
      state). Participants were divided into four schooling groups (illiterate, 1 to 4
      years, 5 to 12 years and 13 years or more). The subjects were divided into four
      groups according to age (50 to 60, 61 to 70, 71 to 80, and 80 years or over).
      RESULTS: Normative data for DRS scores are expressed as percentile values. The
      group with lowest schooling and subjects older than 80 years had the worst
      scores. CONCLUSION: As expected, age and education were strongly correlated with
      DRS scores. Illiterates and older old individuals performed worse than the other
      groups. These data might help to improve the accuracy of the diagnosis of
      cognitive impairment and dementia in Brazilian middle-age and elderly
      populations.

PMID- 29213862
TI  - Communication map of elderly people Sociodemographic and cognitive-linguistic
      aspects.
AB  - : Language and communication difficulties may occur in the elderly population.
      This is the case of the tip-of-the-tongue phenomenon and receptive and auditory
      comprehension difficulties. Few studies have focused on examining the effects of
      social exposure on maintaining communication in the aging process. OBJECTIVES:
      [1] To describe the communication map of healthy elderly subjects; [2] To search
      for associations between frequency and time dedicated to communication and
      cognitive and sociodemographic factors. METHODS: Healthy elderly subjects were
      submitted to cognitive screening, the Token Test - Revised, and the Verbal
      Fluency test, and answered the ASHA-FACS and the Circles of Communication
      Partners questionnaires. RESULTS: 55 subjects, 67% female, with ages over 60
      years and varied schooling were included in the sample. Interlocutors in the
      circle of close friends and acquaintances predominated in the communication map,
      although the time devoted to communication with these partners was lower than in
      other circles. Overall, the elderly reported no deficits in language
      comprehension, with some reports of the tip-of-the-tongue phenomenon. Poor
      performances on the Token Test - Revised and in phonemic verbal fluency along
      with reports of communication functionality indicated that these subjects
      compensate for their problems. CONCLUSION: Older subjects with lower schooling
      tended to predominantly communicate within the family circle. Within other
      circles, the number of hours devoted to communication and dialogue partners was
      not associated with age or schooling. The time devoted to the circle of
      communication with friends may indicate cognitive difficulties.

PMID- 29213863
TI  - Translation, cross-cultural adaptation and applicability of the Brazilian version
      of the Frontotemporal Dementia Rating Scale (FTD-FRS).
AB  - BACKGROUND: Staging scales for dementia have been devised for grading Alzheimer's
      disease (AD) but do not include the specific symptoms of frontotemporal lobar
      degeneration (FTLD). OBJECTIVE: To translate and adapt the Frontotemporal
      Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese. METHODS: The cross
      cultural adaptation process consisted of the following steps: translation, back
      translation (prepared by independent translators), discussion with specialists,
      and development of a final version after minor adjustments. A pilot application
      was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for
      disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's
      Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE),
      Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal
      Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR).
      RESULTS: The Brazilian version of the FTD-FRS seemed appropriate for use in this
      country. Preliminary results revealed greater levels of disability in bvFTD than
      in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild,
      63.64% moderate). It appears that the CDR underrates disease severity in bvFTD
      since a relevant proportion of patients rated as having mild dementia (CDR=1.0)
      in fact had moderate or severe levels of disability according to the FTD-FRS.
      CONCLUSION: The Brazilian version of the FTD-FRS seems suitable to aid staging
      and determining disease progression.

PMID- 29213864
TI  - Cognitive and renal dysfunction in the elderly.
AB  - : Cognitive impairment has been associated with several diseases and organic
      disturbances but few studies have explored the relationship between renal
      function and cognition. OBJECTIVE: The aim of this study was to compare the renal
      function of elderly patients with and without Alzheimer's disease, and to
      identify potential associated comorbidities, as well as the presence of
      microalbuminuria. METHODS: A group of 60 patients with dementia syndrome and
      probable Alzheimer's disease, and 20 patients without dementias, followed at the
      Geriatric outpatient unit of the Santa Casa de Sao Paulo Hospital, were selected
      for this study. RESULTS: The results showed that the groups studied differed in
      terms of age, gender and Mini-Mental State Exam score, but no statistical
      difference was found for the presence of comorbidities (diabetes mellitus,
      dyslipidemia and systemic arterial hypertension). A significant difference in
      estimated creatinine clearance was observed between the two groups, with the
      Alzheimer's disease patients presenting significantly lower values than control
      subjects. Similarly, analysis of a portion of the two groups for the presence of
      microalbuminuria revealed a statistically significant difference between the two
      groups. CONCLUSION: The study conclusions were that patients with Alzheimer's
      disease had lower glomerular filtration and a higher incidence of
      microalbuminuria, yet without having more classic risk factors for Alzheimer's
      disease such as systemic arterial hypertension, diabetes mellitus or
      dyslipidemia.

PMID- 29213865
TI  - The association between nutritional status and cognitive impairment in brazilian
      community-dwelling older adults assessed using a range of anthropometric measures
      - the Bambui study.
AB  - : In most studies, body mass index (BMI) has been used as the main measurement of
      nutritional status. However, BMI does not differentiate between body fat and
      muscle mass. OBJECTIVE: To investigate the association between nutritional status
      and cognitive impairment in a population of Brazilian elderly. METHODS:
      Participants (n=1,496) from the Bambui Cohort Study of Aging were selected based
      on the results for the two variables nutritional status and cognitive impairment
      (MMSE score). Gender, age, education, lifestyle, ApoE, chronic diseases,
      depressive symptoms, current use of hypnotic or sedative medication and
      functional disability were used as confounding factors for adjusting the logistic
      regression. RESULTS: Cognitive impairment was associated with lower BMI (OR:
      0.91; CI: 0.86-0.95), waist circumference (OR: 0.97; CI: 0.95-0.99), triceps
      skinfold thickness (OR: 0.92; CI: 0.89-0.96) among the younger participants (60
      69 years), while lower arm muscle circumference (OR: 0.88; CI: 0.80-0.98) and
      corrected arm muscle area (OR: 0.96; CI: 0.93-0.99) were associated with
      cognitive impairment among the older participants (70 years and over).
      CONCLUSION: There was a difference of association between anthropometric measures
      and cognitive impairment after stratifying by age group. In the group aged
      between 60 and 69, cognitive impairment was associated with measures related to
      fat mass, while in the group aged over 70, cognitive impairment was associated
      with measures related to muscle mass. This finding suggests that investigation of
      nutritional status in the elderly using anthropometric measures should not be
      restricted only to the use of BMI, and should also, differ according to age.

PMID- 29213866
TI  - Cognitive abilities screening instrument-short form, mini-mental state
      examination and functional activities questionnaire in the illiterate elderly.
AB  - : Dementia prevalence is increasing in developing countries due to population
      aging. Brief tests for assessing cognition and activities of daily living are
      very useful for the diagnosis of dementia by the clinician. Low education,
      particularly illiteracy, is a hindrance to the diagnosis of dementia in several
      regions of the world. OBJECTIVES: To compare the Brazilian version of the
      Cognitive Abilities Screening Instrument-Short Form (CASI-S) with the Mini-Mental
      State Examination (MMSE) and Pfeffer Functional Activities Questionnaire (PFAQ)
      for the diagnosis of dementia in illiterate elderly. METHODS: A cross-sectional
      study with illiterate elderly of both genders seen at the outpatient clinics of
      the Institute of Gerontology and Geriatrics Jundiai, Sao Paulo state was
      performed. Spearman's correlation coefficient was used to correlate CASI-S, MMSE
      and PFAQ scores. RESULTS: The sample comprised 29 elderly over 57 years old whose
      mean scores on the CASI-S (scores ranging from 3 to 23) and the MMSE (scores
      ranging from 2 to 23) were 11.69 and 12.83, respectively. There was a strong
      significant correlation between the CASI-S and MMSE (r=0.75, p<0.001) and a
      moderate correlation coefficient that was significant and negative between the
      PFAQ and CASI-S (r= -0.53 p=0.003),similar to that between the MMSE and PFAQ (r= 
      0.41 p=0.025). CONCLUSION: The Brazilian version of the CASI-S demonstrates ease
      of application and correction in the illiterate elderly, and warrants further
      studies regarding its applicability for the diagnosis of dementia in populations
      with a heterogeneous educational background.

PMID- 29213867
TI  - Diagnostic use of neuro-spect quantified with 99mTc-ECD a model based on normal
      data.
AB  - OBJECTIVE: The purpose of the present study was to prospectively quantify the
      normal limits of brain perfusion using specific software in a group of
      asymptomatic young volunteers submitted to single-photon emission tomography
      (SPECT) with 99mTc-ethyl cysteinate dimer (99mTc-ECD). METHODS: We used 15 MBq/kg
      of intravenous 99mTc-ECD in 30 healthy volunteers submitted to brief
      neuropsychological tests and a clinical questionnaire. These data were normalized
      relative to the cerebellum (Group 1) and to the brain cortex (Group 2).
      Statistical analysis was performed with Student's t-test. The average
      radioactivity was 6.5 million counts/study. RESULTS: The normalized (Group I)
      revealed an average value of 78.03%, with standard deviation (SD) of 4.07. Two
      volunteers in this group had slightly greater than two standard deviations from
      the mean. When we used (Group II), the average value was 71.01%, with a SD of
      4.66. We observed a difference between groups of 9% (P<0.001). CONCLUSION: The
      present study suggests normal cortical perfusional values for a group of young
      asymptomatic volunteers, utilizing 99mTc-ECD. This allows further quantification
      of neuro-SPECT data, specifically comparisons across patient populations.
      Furthermore, this method represents a new tool that can be used to further
      explore the field of neuroimaging, particularly neuropsychiatry.

PMID- 29213868
TI  - Non-literal language and semantic dementia.
AB  - : Semantic dementia is characterized by fluent, phonologically adequate speech
      with various anomias and semantic paraphasias. Performance on semantic tasks is
      well documented in these patients, although little is known regarding performance
      on more complex language tasks, such as those involving non-literal language
      (interpretation of metaphors and proverbs and recognition of irony). OBJECTIVE:
      To report the investigation of non-literal language in cases of semantic
      dementia. METHODS: Two cases of semantic dementia were investigated for the
      presence of deficits in non-literal language abilities using the screening test
      for Alzheimer's disease with proverbs, metaphor test and irony test. RESULTS:
      Both patients were found to have low performance on the tests applied,
      particularly for interpretation of proverbs. CONCLUSION: This poor performance
      was attributed largely to the characteristic semantic changes of the disease, but
      some frontal symptoms inherent to other forms of frontotemporal lobar
      degeneration were also observed which interfered in the testing, such as
      negativism, reduced attention span, concretism and perseverations.

PMID- 29213869
TI  - Rapidly progressive dementia due to neurosarcoidosis.
AB  - : Rapidly progressive dementia (RPD) is typically defined as a cognitive decline
      progressing to severe impairment in less than 1-2 years, typically within weeks
      or months. Accurate and prompt diagnosis is important because many conditions
      causing RPD are treatable. Neurosarcoidosis is often cited as an unusual
      reversible cause of RPD. METHODS: We report two cases of neurosarcoidosis
      presenting as RPD. RESULTS: Case 1: A 61-year-old woman developed a RPD
      associated with visual loss. In seven months she was dependent for self-care.
      Magnetic resonance imaging (MRI) revealed temporal and suprasellar brain lesions.
      Treatment with high-dose intravenous prednisolone was associated with partial
      improvement. Case 2: A 43-year-old woman who was being treated for diabetes
      insipidus developed a severe episodic amnesia one year after onset of cognitive
      symptoms. Previous MRI had shown a hypothalamic lesion and she had been treated
      with oral prednisone and cyclophosphamide. There was reduction of the MRI
      findings but no improvement in the cognitive deficits. Brain biopsy disclosed
      noncaseous granulomas and granulomatous angiitis; treatment was changed to high
      dose intravenous methylprednisolone, with poor symptomatic response. CONCLUSION:
      The diagnosis of RPD due to neurosarcoidosis can be challenging when the disease
      is restricted to the nervous system. In these cases, clinical presentation of RPD
      associated with neuroendocrine and visual dysfunction, imaging findings showing
      hypothalamic lesions and, in some cases, brain biopsy, are the key to a correct
      diagnosis. It is possible that earlier diagnoses and treatment could have led to
      a better outcome in these patients.

PMID- 29213870
TI  - Meynert and the basal nucleus.
AB  - Meynert described the "loop of the peduncular foot" (Schlinge des
      Hirnschenkelfusses), and its ganglion (Ganglion der Hirnschenkelschlinge) and
      related them to Reil's Substantia innominata and Gratiolet's Ansa peduncularis,
      from which he apparently built up his findings. Koelliker renamed the ganglion
      with the eponymous designation Meynert'sches Basalganglion (Meynert's basal
      ganglion), a name which endures to the present day, and described its
      topographical spread in relation to neighboring structures. Meynert and Koelliker
      also described aspects of cell composition of the ganglion (or nucleus) with a
      better account of the latter. Both, together with Reil and Gratiolet, were the
      outstanding personalities of the 19th century who performed the pioneering
      studies on basal formations of the forebrain. After these works, a considerable
      body of research appeared in the 20th century, with a focus on Meynert's basal
      nucleus and related structures. The development of further knowledge about these
      structures revealed their great importance in the activity of the brain, as
      evidenced in both normal and pathological states.

PMID- 29213872
TI  - In the March 2014 issue.

PMID- 29213871
TI  - Encephalomyelopathy associated with HTLV-I a primary disease or coexisting with
      multiple sclerosis?
AB  - HTLV-I-associated myelopathy (HAM/TSP) is the most common neurological
      manifestation of HTLV-I, causing progressive weakness, sensory disturbance, and
      sphincter dysfunction. Although motor disorders have been well described, few
      studies have associated cognitive disorders and HTLV-I infection. In areas
      endemic for HTLV-I infection, the differential diagnosis between HAM/TSP and
      other myelopathy etiologies can be difficult, particularly if the patient has
      signs and symptoms of brain involvement, since seropositive HTLV-I patients can
      present other neurological diseases. Here, we report one case initially diagnosed
      as Multiple Sclerosis (MS) which, upon further investigation, was found to be
      HTLV-I seropositive.

PMID- 29213873
TI  - Action/Verb processing: Debates in neuroimaging and the contribution of studies
      in patients with Parkinson's disease.
AB  - The objective of the current review was to verify whether studies investigating
      lexical-semantic difficulties in patients with Parkinson's disease (PD) support
      the Embodied Cognition model. Under this framework, it is predicted that patients
      with PD will have more difficulties in the semantic processing of action concepts
      (action verbs) than of motionless objects. We also verified how and whether these
      studies are following current debates of Neuroscience, particularly the debate
      between the Lexical and the Embodied Cognition models. Recent neuroimaging
      studies on the neural basis of the semantics of verbs were presented, as well as
      others that focused on the neural processing of verbs in PD. We concluded that
      few studies suitably verified the Embodied Cognition theory in the context of PD,
      especially using neuroimaging techniques. These limitations show there is much to
      investigate on the semantic difficulties with action verbs in these patients,
      where it is particularly important to control for psycholinguistic variables and
      the inherent semantic characteristics of verbs in future studies.

PMID- 29213874
TI  - Sport-related concussions.
AB  - Traumatic brain injury (TBI) is a major cause of lifelong disability and death
      worldwide. Sport-related traumatic brain injury is an important public health
      concern. The purpose of this review was to highlight the importance of sport
      related concussions. Concussion refers to a transient alteration in consciousness
      induced by external biomechanical forces transmitted directly or indirectly to
      the brain. It is a common, although most likely underreported, condition. Contact
      sports such as American football, rugby, soccer, boxing, basketball and hockey
      are associated with a relatively high prevalence of concussion. Various factors
      may be associated with a greater risk of sport-related concussion, such as age,
      sex, sport played, level of sport played and equipment used. Physical complaints
      (headache, fatigue, dizziness), behavioral changes (depression, anxiety,
      irritability) and cognitive impairment are very common after a concussion. The
      risk of premature return to activities includes the prolongation of post
      concussive symptoms and increased risk of concussion recurrence.

PMID- 29213875
TI  - Addenbrooke's Cognitive Examination-Revised is accurate for detecting dementia in
      Parkinson's disease patients with low educational level.
AB  - : Diagnosis of Parkinson's disease dementia is a challenge in clinical settings.
      A comprehensive neuropsychological evaluation is time-consuming and expensive;
      brief instruments for cognitive evaluation must be easier to administer and
      provide a reliable classification. Objective: To study the validity of the
      Brazilian version of Addenbrooke's Cognitive Examination-Revised (ACE-R) for the
      cognitive assessment of Parkinson's disease (PD) patients with heterogeneous
      educational level. Methods: Patients were evaluated according to the diagnostic
      procedures recommended by the Movement Disorder Society (MDS) as the gold
      standard for the diagnosis of dementia in PD. Results: We studied 70 idiopathic
      PD patients, with a mean (SD) age of 64.1 (9.3) years and mean disease duration
      of 7.7 (5.3) years and educational level of 5.9 years, matched for education and
      age to controls. Twenty-seven patients fulfilled MDS clinical criteria for PD
      dementia. Mean scores on the ACE-R were 54.7 (12.8) points for patients with PD
      dementia, 76 (9.9) for PD patients without dementia and 79.7 (1.8) points for
      healthy controls. The area under the receiver operating curve, taking the MDS
      diagnostic procedures as a reference, was 0.93 [95% CI, 0.87-0.98; p<0.001] for
      ACE-R. The optimal cut-off value for ACE-R was <=72 points [sensitivity 90%;
      specificity 85%; Kappa concordance (K) 0.79]. Conclusion: ACE-R appears to be a
      valid tool for dementia evaluation in PD patients with heterogeneous educational
      level, displaying good correlation with clinical criteria and diagnostic
      procedures of the MDS.

PMID- 29213876
TI  - Performance of an adult Brazilian sample on the Trail Making Test and Stroop
      Test.
AB  - Objective: The Trail Making Test (TMT) and Stroop Test (ST) are attention tests
      widely used in clinical practice and research. The aim of this study was to
      provide normative data for the adult Brazilian population and to study the
      influence of gender, age and education on the TMT parts A and B, and ST cards A,
      B and C. Methods: We recruited 1447 healthy subjects aged >=18 years with an
      educational level of 0-25 years who were native speakers of Portuguese
      (Brazilian). The subjects were evaluated by the Matrix Reasoning and Vocabulary
      subtests of the Wechsler Adult Intelligence Scale-III, along with the TMTA, TMTB
      and ST A, B and C. Results: Among the participants, mean intellectual efficiency
      was 103.20 (SD: 12.0), age 41.0 (SD: 16.4) years and education 11.9 (SD: 5.6)
      years. There were significant differences between genders on the TMTA (p=0.002),
      TMTB (p=0.017) and STC (p=0.024). Age showed a positive correlation with all
      attention tests, whereas education showed a negative correlation. Gender was not
      found to be significant on the multiple linear regression model, but age and
      education maintained their interference. Conclusion: Gender did not have the
      major impact on attentional tasks observed for age and education, both of which
      should be considered in the stratification of normative samples.

PMID- 29213877
TI  - Executive function and processing speed in Brazilian HIV-infected children and
      adolescents.
AB  - Background: Cognitive disorders in infants and children who are vertically
      infected with human immunodeficiency virus (HIV) have been recognized since the
      inception of the epidemic. Objective: The present study investigated
      neuropsychological performance in a cohort of vertically infected Brazilian
      children and adolescents who underwent antiretroviral therapy. The
      neuropsychological tasks were designed to evaluate executive function and
      processing speed. Methods: Children and adolescents were recruited at a major
      research and treatment reference center for human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV) in Minas Gerais, Brazil. Forty-one individuals
      aged 5 to 17 years were enrolled. Twelve were mildly symptomatic (HIV-infected
      group, Centers for Disease Control and Prevention [CDC] class A or B), and 29 had
      advanced clinical disease (AIDS group, CDC class C). Results: The results showed
      that HIV-infected children and adolescents exhibited lower performance on
      neuropsychological tasks than sociodemographically comparable, typically
      developing controls. Motor and cognitive processing speed and executive function
      appeared to be the most discriminative domains. Conclusion: HIV-infected
      individuals with more-advanced disease stages exhibited lower performance levels
      and had greater performance heterogeneity on neuropsychological tasks. Thus, the
      observed neuropsychological impairments, although more pronounced in participants
      with more advanced stages of the disease, did not correlate with the variable
      used (CDC stage).

PMID- 29213878
TI  - Dementia care in public health in Brazil and the world: A systematic review.
AB  - Objective: This study aimed to identify in the recent scientific literature,
      information on health care provided to people with dementia, dementia costs and
      its resource implications for public health. Methods: This was a systematic
      review of the literature in which the articles were consulted from the databases
      PubMed/MEDLINE, LILACS and SciELO. The review sample consisted of 45 articles.
      Results: Examination of the studies identified the current scenario of dementia
      in relation to public health and public policy in Brazil and the world. The
      analyzed studies revealed key information on aspects of dementia in the world.
      There was consensus on the high prevalence of the syndrome and on the significant
      cost of health care and public policy for assisting the elderly with dementia.
      Conclusion: The importance of planning and implementing new public policies was
      recognized, since these are essential for the organization and management of
      health services and directly influence the country's ability to provide health
      care for people with dementia.

PMID- 29213879
TI  - The Basis and Applications of the Action Fluency and Action Naming Tasks.
AB  - : The Action Fluency (AF) and Action Naming (AN) are different tasks involving
      verb generation. Evidence indicates that verb tasks yield different information
      from that obtained with nouns. Objective: This study aimed to analyze the
      information available in the scientific literature on the mechanism and clinical
      application of these tasks. Methods: We carried out a systematic review of the
      literature and the findings were presented according to clinical studies and
      neuroimaging studies, and to the task in question. Results: The literature
      contained a variety of relevant studies with different objectives, methodologies
      and populations. After the analysis (exclusion criteria) of the studies obtained
      by the search terms, only 40 studies were included in this review. Conclusion: It
      was possible to conclude that AF and AN involve different brain processes, and
      although recruiting frontal areas and circuits, other areas are also critical.
      These tasks may be useful for differentiating Primary Progressive Aphasias; AF
      might represent a new measure of executive function; finally, both these tests
      can be used to provide a better understanding of cognitive processes and certain
      diseases.

PMID- 29213880
TI  - Rehabilitation of discourse impairments after acquired brain injury.
AB  - : Language impairments in patients with acquired brain injury can have a negative
      impact on social life as well as on other cognitive domains. Discourse
      impairments are among the most commonly reported communication deficits among
      patients with acquired brain damage. Despite advances in the development of
      diagnostic tools for detecting such impairments, few studies have investigated
      interventions to rehabilitate patients presenting with these conditions.
      Objective: The aim of this study was to present a systematic review of the
      methods used in the rehabilitation of discourse following acquired brain injury.
      Methods: The PubMed database was searched for articles using the following
      keywords: "rehabilitation", "neurological injury", "communication" and
      "discursive abilities". Results: A total of 162 abstracts were found, but only
      seven of these met criteria for inclusion in the review. Four studies involved
      samples of individuals with aphasia whereas three studies recruited samples of
      individuals with traumatic brain injury. Conclusion: All but one article found
      that patient performance improved following participation in a discourse
      rehabilitation program.

PMID- 29213881
TI  - Epilepsy in patients with Alzheimer's disease: A systematic review.
AB  - : Alzheimer's disease (AD) and epilepsy are common disorders in the elderly.
      Evidence demonstrates that patients with AD have an increased risk of developing
      epilepsy and seizures. Objective: To review epidemiological, clinical and
      treatment aspects of epilepsy and AD. Methods: We reviewed databases (PubMED,
      LiLACS, Scielo) conducting a search for manuscripts using the terms Alzheimer's
      disease and epilepsy. Results: Manuscripts related to the areas of interest were
      reviewed. Studies revealed that epilepsy is more frequent among AD patients. The
      combined presence of the two disorders may be related to mechanisms of neuronal
      hyperexcitability as a consequence of amyloid-beta protein (Abeta) or
      phosphorylated tau accumulation, as well as to structural changes in cortical and
      hippocampal regions. Available data suggest that the new generation of
      antiepileptic drugs (AEDs) are better tolerated in the elderly population, and
      may also be the best option in patients with AD and epilepsy. Conclusion: Further
      prospective studies involving evaluation of concomitant dementia and epilepsy,
      neurophysiological findings and biomarkers need to be performed.

PMID- 29213882
TI  - Performance of patients with frontotemporal lobar degeneration on artistic tasks:
      A pilot study.
AB  - : Several studies have addressed visuospatial and executive skills in artistic
      activities in Frontotemporal Lobar Degeneration (FTLD) and Alzheimer's disease
      (AD). Objective: To investigate the performance of FTLD patients compared to
      controls on two artistic tasks. Methods: Four FTLD patients with mean age of 57
      (8.7) years and schooling of 12.2 (4.5) years plus 10 controls with mean age of
      62.9 (8.6) years and schooling of 12.3 (4.6) years, were assessed using the
      Lowenstein Occupational Therapy Cognitive Assessment (LOTCA) and by a three-stage
      artistic protocol including visual observation, copying and collage, based on a
      Sisley painting. Results: FTLD patients had lower scores than controls on
      Visuospatial Perception, Copy, Collage, Examiner's Observation, and Total,
      showing distinct patterns of performance according to FTLD sub-type: semantic
      PPA, nonfluent PPA and bvFTD. Conclusion: FTLD patients presented impairment in
      the visuospatial and executive skills required to perform artistic tasks. We
      demonstrated that the application of the instrument as a complimentary method for
      assessing cognitive skills in this group of patients is possible. Further studies
      addressing larger and more homogeneous samples of FTLD patients as well as other
      dementias are warranted.

PMID- 29213883
TI  - Brown-Sequard: On neural networks and brain localization of functions.
AB  - The notion that the brain (encephalon) is a network of interconnected neurons has
      a long and memorable history. Cytoarchitectonic and hodological studies coupled
      with advanced neuroimaging techniques have produced a substantial body of
      knowledge on structural and functional organization. Acquiring the rich knowledge
      held today took a long and winding journey. Important advancements were made in
      the 19th century, with the remarkable Brown-Sequard figuring as one of the
      protagonists. Regarding the brain, he proposed nine mental and physical functions
      (organs) related to distributed cell clusters, interconnected according to their
      roles, the "network of anastomosing cells", dynamically submitted to "dynamogenic
      and inhibitory activities", and "action at a distance" concepts, the latter also
      related to his notion of "recovery". It is remarkable that someone was able to
      propose, ahead of his time, and with the limited technical resources available,
      such significant concepts that paved the way for the current state of knowledge.

PMID- 29213884
TI  - Frontotemporal dementia and amyotrophic lateral sclerosis: revisiting one of the
      first case reports with neuropathology examination.
AB  - The occurrence of dementia in amyotrophic lateral sclerosis (ALS) was only widely
      recognized in the late 20th century. Hitherto, it was believed that dementia was
      a rare event due to the fortuitous association with other diseases. In 1924,
      Kostantin Nikolaevich Tretiakoff and Moacyr de Freitas Amorim reported a case of
      dementia with features of frontotemporal dementia (FTD) that preceded the motor
      signs of ALS. Neuropathological examination confirmed ALS and found no signs of
      other dementia-causing diseases. The authors hypothesized that dementia was part
      of ALS and recommended the search for signs of involvement of motor neurons in
      cases of dementia with an ill-defined clinical picture, a practice currently
      accepted in the investigation of cases of FTD. This was one of the first
      descriptions of dementia preceding the motor impairments of ALS and was published
      in Portuguese and French in Memorias do Hospicio de Juquery.

PMID- 29213885
TI  - A successful case of anti-NMDAR encephalitis without tumor treated with a
      prolonged regimen of plasmapheresis.
AB  - Anti-NMDA receptor encephalitis is a severe but treatable autoimmune disease of
      the CNS. However, the use of immunotherapy and long-term outcomes have yet to be
      defined for this disease. We describe a case of an 18-year-old male diagnosed
      with anti-NMDAR encephalitis not associated with tumor, which did not respond to
      initial treatment with immunoglobulin, followed by corticosteroids,
      cyclophosphamide and evolved with significant clinical improvement after a
      prolonged course of plasmapheresis. Although it is not possible to affirm the
      good outcome was due solely to the prolonged plasmapheresis regimen, recently
      published data shows that improvement may take weeks or months to occur. This
      case discloses another therapeutic possibility for patients with refractory
      disease who fail to respond to recommended first-line and second-line therapy.

PMID- 29213886
TI  - Anterior portion of the cingulate gyrus: A novel location for transient global
      amnesia?
AB  - Transient global amnesia (TGA) is characterized by abrupt transient loss of
      anterograde memory, lasting up to 24 hours, and no other focal neurological
      signs. We report the case of a right-handed 71-year-old female patient who
      presented temporal-spatial disorientation 5 minutes after ingestion of 1000 ml of
      iodinated contrast. The patient had mild temporal-spatial disorientation, with
      significant deficit in anterograde memory. After 12 hours under observation, the
      patient progressed to gradual improvement and was discharged. A reevaluation
      after 15 days showed normal cortical functions, score on mini-mental state exam
      of 30, and unaffected working and recall memory. MRI performed 48 hours after the
      event showed hypersignal in the diffusion sequence in the anterior portion of the
      cingulate gyrus, with hypointense signal in MAP/ADC, confirming a finding
      consistent with TGA. No previous reports in the literature have described the
      location affected in this patient, rendering it a novel site consistent with this
      diagnosis.

PMID- 29213887
TI  - In the June 2014 issue.

PMID- 29213888
TI  - Overcoming barriers in cognitive assessment of Alzheimer's disease.
AB  - Diagnosis of Alzheimer's disease (AD) requires a reliable neuropsychological
      assessment, but major barriers are still encountered when such tests are used
      across cultures and during the lifespan. This is particularly problematic in
      developing countries where most of the available assessment tools have been
      adapted from developed countries. This represents a major limitation as these
      tests, although properly translated, may not embody the wealth of challenges that
      a particular culture poses on cognition. This paper centers on two shortcomings
      of available cognitive tests for AD, namely, their sensitivity to the educational
      background and to the age of the individual assessed.

PMID- 29213889
TI  - Instruments for assessing pain in persons with severe dementia.
AB  - Through an integrative literature review involving the CINAHL, Cochrane, Embase,
      LILACS, PsycINFO, PubMed databases, tools available in the literature for
      assessing pain in individuals with severe dementia were identified along with
      versions validated for use in Brazil. We found 1501 relevant articles which,
      after selection of abstracts and full reading, yielded a final sample of 33
      articles. The analysis enabled the identification of 12 instruments: ABBEY PAIN
      SCALE; ADD; CNPI; CPAT; DOLOPLUS-2; MOBID and MOBID-2; MPS; NOPPAIN; PACSLAC;
      PADE; PAINAD and PAINE. Despite the wide variety of tools for assessing pain in
      individuals with severe dementia worldwide, it was observed that only four are
      available in Portuguese, of which two are culturally adapted for Brazilian
      Portuguese (NOPPAIN and PACSLAC) and two validated for Portuguese of Portugal
      (DOLOPLUS and PAINAD), pointing to the need for further validation of instruments
      for use in Brazil.

PMID- 29213890
TI  - Use of computerized tests to assess the cognitive impact of interventions in the
      elderly.
AB  - With the aging of the population, the possibility of the occurrence of cognitive
      decline rises. A number of types of intervention seek to attenuate or reverse
      this impairment. The use of computerized tests helps quantify the effects of
      interventions on cognitive function in the elderly. The objective of the present
      review was to analyze studies that have utilized computerized cognitive tests to
      determine the effects of interventions in the elderly population, describing the
      batteries and tests employed, the populations studied and reports by authors on
      the limitations or benefits of employing these tests in older adults. The review
      was performed on the PubMed database using the descriptors: cognitive
      computerized test and elderly. We retrieved 530 studies and, following analysis
      of their abstracts, selected 32 relevant to the subject. The studies utilized 19
      different types of computerized tests and batteries to assess the interventions,
      which were predominantly drug trials. There were no reports on limitations in the
      use of the computerized tests, suggesting this type of intervention had good
      applicability, sensitivity, and little or no practice effects in this population.

PMID- 29213891
TI  - Computerized Neurocognitive Test (CNT) in mild cognitive impairment and
      Alzheimer's disease.
AB  - Currently, computerized batteries are of great value in detecting cognitive
      impairment. This aim of this review was to compare the computerized
      neurocognitive batteries used in most studies with cognitive decline over the
      last 10 years. Using the search words computerized cognitive assessment with:
      dementia, mild cognitive impairment, and Alzheimer's disease, the CogState, CNS
      Vital Sings, COGDRAS and Mindstreams batteries were retrieved.

PMID- 29213892
TI  - The association between educational level and dementia in rural Tanzania.
AB  - : The majority of people with dementia worldwide live in developing countries.
      Studies from the developed world have reported an association between lower
      educational attainment and dementia, but there are few data from the developing
      world where literacy and educational levels are frequently much lower. In this
      study we assessed the association between education and dementia prevalence in a
      rural Tanzanian setting. Methods: In phase I, 1198 individuals aged 70 and over
      were assessed using the Community Screening Instrument for Dementia (CSI-D). In
      phase Ii a stratified sample of those seen in phase I were fully assessed and a
      clinical diagnosis based on DSM-IV criteria was made where appropriate.
      Information regarding literacy, highest attained educational level and occupation
      were also collected. Results: The median subject cognitive score on the CSI-D was
      25.7 (IQR 22.7 to 28.0) for females and 27.7 (IQR 25.7 to 29.4) for males. This
      difference was significant (U=117770.0, z= -9.880, p<0.001). In both males and
      females a lower CSI-D subject cognitive score was significantly associated with
      having had no formal education (U=34866.5, z= -6.688, p<0.001, for females;
      U=20757.0, z= -6.278, p<0.001, for males). After adjusting for the effect of age,
      having no formal education was significantly associated with greater odds of
      having 'probable dementia' by CSI-D, as was illiteracy. Amongst those interviewed
      in phase II, there was no significant difference in literacy or education between
      those with diagnosed DSM-IV dementia and those without. Conclusion: In this rural
      Tanzanian population, we found a significant association between low levels of
      education and dementia by CSI-D. This relationship was not significant in cases
      meeting DSM-IV criteria for dementia.

PMID- 29213893
TI  - Features associated with cognitive impairment and dementia in a community-based
      sample of illiterate elderly aged 75+ years: the Pieta study.
AB  - : A higher level of educational attainment constitutes a protective factor
      against cognitive decline in the elderly. Nevertheless, the elements underpinning
      this association are yet not fully understood. Objective: The primary aim of this
      study was to compare cognitively impaired illiterate elderly subjects with
      cognitively preserved counterparts, according to demographics, comorbidities,
      lifetime habits and APOE genotype. Methods: This is a cross-sectional analysis of
      the illiterate subset of participants (n=174) from the Pieta study, a community
      based survey of successful brain aging conducted in Caete (MG), Brazil. Subjects
      were categorized into three diagnostic groups: cognitively normal (CN), cognitive
      impairment no-dementia (CIND) and dementia. The groups were then compared
      according to selected variables. Results: Subjects with dementia were older and
      had an increased prevalence of reported stroke or transient ischemic attack. The
      three groups did not differ in relation to demographics, prevalence of
      comorbidities, socioeconomic level, previous occupation profile and APOE-epsilon4
      allele frequency. Qualitatively evaluated lifetime habits, such as alcohol
      consumption, smoking and physical activity engagement were also similar across
      groups. Conclusion: No associations were found between cognitive
      impairment/dementia and the variables evaluated in this community-based sample of
      illiterate elderly.

PMID- 29213894
TI  - Dementia in developing countries: Does education play the same role in India as
      in the West?
AB  - : Evidence suggests that education protects from dementia by enhancing cognitive
      reserve. However, this may be influenced by several socio-demographic factors.
      Rising numbers of dementia in India, high levels of illiteracy and heterogeneity
      in socio-demographic factors provide an opportunity to explore this relationship.
      Objective: To study the association between education and age at dementia onset,
      in relation to socio-demographic factors. Methods: Association between age at
      dementia onset and literacy was studied in relationship to potential confounding
      factors such as gender, bilingualism, place of dwelling, occupation, vascular
      risk factors, stroke, family history of dementia and dementia subtypes. Results:
      Case records of 648 dementia patients diagnosed in a specialist clinic in a
      University hospital in Hyderabad, India were examined. All patients were
      prospectively enrolled as part of an ongoing longitudinal project that aims to
      evaluate dementia subjects with detailed clinical, etiological, imaging, and
      follow-up studies. Of the 648 patients, 98 (15.1%) were illiterate. More than
      half of illiterate skilled workers were engaged in crafts and skilled agriculture
      unlike literates who were in trade or clerical jobs. Mean age at onset in
      illiterates was 60.1 years and in literates 64.5 years (p=0.0002). Factors
      independently associated with age at dementia onset were bilingualism, rural
      dwelling and stroke, but not education. Conclusion: Our study demonstrates that
      in India, rural dwelling, bilingualism, stroke and occupation modify the
      relationship between education and dementia.

PMID- 29213895
TI  - A systematic review and meta-analysis of the diagnostic accuracy of the Phototest
      for cognitive impairment and dementia.
AB  - : The recently developed Phototest is a simple, easy and very brief test for
      detecting cognitive impairment or dementia. Objective: To evaluate the diagnostic
      accuracy of the Phototest for detecting cognitive impairment or dementia.
      Methods: We used a manually created database to search for studies evaluating the
      Phototest diagnostic yield and performed an initial meta-analysis to determine
      sensitivity (Sn) and specificity (Sp) of diagnostic parameters. We also performed
      a second meta-analysis of individual participant data. Results: In total, 6
      studies were included in the meta-analysis. For dementia, Sn was 0.85 (95% CI,
      0.82-0.88) and Sp 0.87 (95% CI, 0.85-0.99); for cognitive impairment, Sn was 0.80
      (95% CI, 0.77-0.92) and Sp 0.88 (95% CI, 0.86-0.90). In the individual data meta
      analysis, 1565 subjects were included, where best cut-off points for dementia and
      for cognitive impairment were 26/27 (Sn=0.89 (95% CI 0.85-0.91), Sp=0.84 (95% CI,
      0.82-0.91)) and 28/29 (Sn=0.79 (95% CI, 0.76-0.81), Sp=0.88 (95% CI, 0.86-0.90)),
      respectively. Conclusion: Phototest has good diagnostic accuracy for dementia and
      cognitive impairment. It is brief, simple and can be used in illiterate persons.
      This makes it suitable for use in primary care settings and/or in subjects with
      low educational level.

PMID- 29213896
TI  - Age, education and gender effects on neuropsychological functions in healthy
      Indian older adults.
AB  - : It is essential to use culturally appropriate, sensitive and specific tests
      that reflect true cognitive performance. However, several factors including age,
      education and gender can influence neuropsychological test performance.
      Objective: To examine the effects of age, education and gender on
      neuropsychological function in older adults using measures of global cognitive
      screening, attention, working memory, executive functions, memory, construction,
      language and parietal focal signs. Methods: This is a cross sectional normative
      study of 180 community-dwelling normal older adults. All participants were
      screened with the Hindi Mental Status Examination (HMSE), Everyday Activities
      Scale for India (EASI), Edinburgh handedness inventory (EDI) and MINI Screen, and
      followed by a detailed neuropsychological assessment. Results: Stepwise
      regression analysis revealed that education was associated with better
      performance on all the neuropsychological tests. Females performed significantly
      better on measures of memory. Further, most of the illiterate subjects, including
      low educated participants, refused to cooperate on measures of executive
      functioning. Conclusion: Education was found to be the strongest determinant of
      neuropsychological test performance followed by age and gender. Our study
      demonstrates that Indian healthy normal older adults with low education perform
      poorly on measures of planning and working memory. Traditional measures of
      planning and working memory should be avoided or used cautiously in the presence
      of low education. There is an urgent need to develop tasks for measuring
      executive functions, especially in low educated Indian older adults.

PMID- 29213898
TI  - Cognitive output of a neuropsychological stimulation program in an elderly day
      care center with low educated participants: An observational study.
AB  - Objective: In the present paper we present an observational study of the
      implementation of a Neuropsychological Stimulation Program at an Elderly Day Care
      Center in low-educated participants with very similar backgrounds concerning
      social economic status. Methods: The implemented program tackled several
      dimensions, including daily orientation sessions, cognitive stimulation sessions
      twice a week, followed by movement sessions, and structured sessions conducted
      every two weeks. Cognitive Evaluation was performed before and after
      implementation of the program. Results: Results are discussed taking into
      consideration cognitive outputs as well as non-cognitive outputs and the
      specificities of community-based intervention. Conclusion: It was concluded that
      community-based intervention is set to become vital in promoting dementia
      prevention.

PMID- 29213897
TI  - Verbal and visuospatial executive functions in healthy elderly: The impact of
      education and frequency of reading and writing.
AB  - Objective: To assess the predictive role of education and frequency of reading
      and writing habits (FRWH) on the cognitive flexibility, inhibition and planning
      abilities of healthy elderly individuals. Methods: Fifty-seven healthy adults
      aged between 60 and 75 years with 2 to 23 years of formal education were assessed
      as to the frequency with which they read and wrote different types of text, as
      well as their number of years of formal education. Executive functions were
      evaluated using the Hayling Test and the Modified Wisconsin Card Sorting Test
      (MWCST). Results: Weak to moderate positive correlations were found between
      education, FRWH and the number of categories completed in the MWCST, while
      negative correlations were identified between these variables and the number of
      perseverative and non-perseverative errors on the task. Only the FRWH was
      significantly correlated with the number of failures to maintain set. Speed and
      accuracy on the Hayling Test were only correlated with participant education.
      Both education and FRWH significantly predicted performance on the MWCST, and the
      combination of these two variables had a greater predictive impact on performance
      on this task than either of the two variables alone. Variability in scores on the
      Hayling Test was best accounted for by participant education. Conclusion: In this
      sample of elderly subjects, cognitive flexibility was sufficiently preserved to
      allow for adequate performance on verbal tasks, but may have benefitted from the
      additional stimulation provided by regular reading and writing habits and by
      formal education in the performance of more complex non-verbal tasks.

PMID- 29213899
TI  - Factors associated with quality of life in elderly undertaking literacy programs.
AB  - : Increased life expectancy has led to a significant number of elderly enrolling
      on Youth and Adult Education programs (YAE). These individuals leave inactivity
      and negative aspects of aging in search of opportunities for social inclusion.
      Objective: To evaluate the influence of sociodemographic factors and depressive
      and cognitive symptoms on quality of life (QL) of elderly attending the YAE of
      Sao Carlos city in Sao Paulo state. Methods: A descriptive and quantitative study
      approved by the Research Ethics Committee of Sao Carlos Federal University was
      conducted. The sample comprised all elderly undertaking the YAE literacy program
      in 2012. The instruments used were the Mini-Mental State Examination (MMSE),
      Geriatric Depression Scale (GDS), WHOQOL-bref and WHOQOL-old, and a
      sociodemographic instrument. Results: We interviewed 23 elderly, predominantly
      females (91.3%) in the early stages of old age (69.6%). The number of years of
      YAE study showed no correlation with cognition scores obtained on the MMSE or
      with QL domains. However, scores on the GDS had a moderate inverse relationship
      with total scores for the Physical (p<0.01), Sensory Functioning (p<0.05),
      Independence (p<0.01), Past, Present and Future Activities (p<0.05), Social
      Participation (p<0.01), and Intimacy (p<0.05) QV domains, and a strong inversely
      proportional relationship with the Social Relationships QV domain (p<0.01).
      Scores attained on the MMSE showed a moderate and direct relationship with total
      scores on the Independence QL domain (p=0.001). Conclusion: Elderly on literacy
      programs have average quality of life scores. Several QL domains are influenced
      by depression and cognitive symptoms.

PMID- 29213901
TI  - Effect of successful aging on mortality in older individuals: The PALA study.
AB  - : The definition of successful aging and identification of predictors have been
      extensively reviewed, less attention however, has been given to the role of this
      condition on mortality. Objective: To evaluate the effect of aging status (normal
      or successful) on mortality in a South Brazilian population-based cohort,
      adjusted for sociodemographic and clinical variables, and to report the mortality
      rate and causes of death in this population. Methods: The baseline sample
      comprised 345 community-dwelling, independent and healthy Southern Brazilian
      older individuals who were followed for 12 years. Clinical, socio-demographic,
      functional and cognitive variables were assessed at baseline and during the
      follow-up. At baseline, 214 participants fulfilled criteria for successful aging,
      and 131 for normal aging. The main outcome was death. Results: The Cox regression
      model showed an increased risk for mortality in subjects with normal aging
      (HR=1.9; p=0.003) adjusted by age (HR=1.1; p<0.001) and by sex (HR=1.9; p=0.002).
      The overall mortality rate was 41% and the rate was significantly lower among
      successful than normal agers (p=0.001). The main causes of death were
      cardiovascular disease and cancer. Conclusion: Our main finding was an increased
      risk of mortality among normal in comparison with successful aging subjects,
      emphasizing the impact of the heterogeneity of the healthy aging process on
      mortality.

PMID- 29213900
TI  - Visuospatial processing: A review from basic to current concepts.
AB  - Introduction: Visuospatial processing is a fundamental aspect in human cognition,
      belonging to a complex and intricate network. It is, in other words, one of the
      building blocks of an individual's identity and behavior. Objective: To allow an
      overall and updated review of visuospatial processing and its related events, in
      light of new techniques and evidence, focusing on basic concepts of higher
      cortical functions, its pathways and associated systems. Methods: The study was
      conducted based on the national and international databases LILACS, MEDLINE,
      ScieLo and Pubmed; using the search word "visuospatial" in combination with
      "pathway", "processing", "function", "fMRI" and "attention". Results: A total of
      77 references deemed relevant for its historical, conceptual or updated relevance
      were selected out of 1222 retrieved; including English, Spanish and Portuguese
      languages. A critical review was carried out and many new aspects discussed.
      Conclusion: A new functioning and construction of sight processing is being
      shaped, culminating now in a model based on dynamic and integrated interactions
      between pathways and systems.

PMID- 29213902
TI  - Longitudinal effects of physical activity on self-efficacy and cognitive
      processing of active and sedentary elderly women.
AB  - : Previous studies support that regular physical activity in aging contributes as
      a protective factor against cognitive decline and improves mood states. However,
      there is a lack of longitudinal studies in this area. Objective: To observe
      possible changes in cognition related with physical activity. Methods: This study
      reassessed, after one-year period, 31 elderly women divided into two groups,
      sedentary versus active, using behavioral scales and cognitive tests. Results:
      The active group exhibited significantly enhanced performance in general
      cognitive function, particularly on tasks of episodic memory and praxis, and also
      on the mood states scale compared to the sedentary group. The active women also
      reported higher self-efficacy. Conclusion: Long-term physical activity promoted
      improvement on quality of life in the elderly women.

PMID- 29213903
TI  - Language assessment and treatment in the last decade.

PMID- 29213904
TI  - Evolution of language assessment in patients with acquired neurological disorders
      in Brazil.
AB  - The objective of this paper was to describe the evolution of language assessments
      in patients with acquired neurological diseases over a period of around 45 years
      from 1970, when interdisciplinarity in Neuropsychology first began in Brazil, to
      the present day. The first twenty years of data was based on memories of Speech
      Pathology University Professors who were in charge of teaching aphasia. We then
      show the contributions of Linguistics, Cognitive Psychology, as well as
      Psycholinguistic and Psychometric criteria, to language evaluation. Finally, the
      current panorama of adaptations and creations of validated and standardized
      instruments is given, based on a search of the databases Pubmed, Scopus and
      Lilacs. Our closing remarks highlight the diversity in evaluation approaches and
      the recent tendency of language evaluations linked to new technologies such as
      brain imaging and computational analysis.

PMID- 29213906
TI  - Semantic memory for actions as assessed by the Kissing and Dancing Test:
      Education and age effects in cognitively healthy individuals.
AB  - : Action semantics is a relevant part of cognitive-linguistic assessment and the
      "Kissing and Dancing Test" (KDT) has been used extensively for this purpose,
      evidencing clinical distinctions among brain-damaged patients. To enhance its
      use, reference values are necessary, especially for populations with
      heterogeneous educational levels and socioeconomic backgrounds. Objective: To
      analyze the effects of schooling and age on the KDT in cognitively unimpaired
      individuals. Methods: The KDT was applied to seventy-four healthy subjects.
      Sociodemographic factors were investigated through correlational and between
      group analyses. Reference values according to age and schooling were provided.
      Results: KDT performance correlated significantly with schooling (r=0.757,
      p<0.01), age (r=-0.496, p<0.01) and socioeconomic status (r=0.418 p<0.01) but
      these variables were intercorrelated. Correlation with schooling and age remained
      significant when controlling for age and socioeconomic status (r=0.530, p<0.01),
      and for schooling (-0.305,<0.01), respectively. When controlling for schooling,
      correlation between socioeconomic status and KDT was not significant (p=0.164).
      Between-group analyses revealed no age effects. Significant differences were
      found in performance according to educational level. Scores below 39/52 and below
      47/52 (percentile 25) for individuals with 8 or less years of schooling and for
      individuals with 9 or more years of schooling, respectively, seem suggestive of
      an impairment in Action Semantics Processing and shall be further investigated.
      Conclusion: KDT performance was influenced both by age and schooling, indicating
      the need to consider these demographic features as covariates when analyzing
      performance on the test and to adjust cut-off scores according to these
      demographic characteristics in clinical practice.

PMID- 29213905
TI  - Transcranial brain stimulation (TMS and tDCS) for post-stroke aphasia
      rehabilitation: Controversies.
AB  - Transcranial brain stimulation (TS) techniques have been investigated for use in
      the rehabilitation of post-stroke aphasia. According to previous reports,
      functional recovery by the left hemisphere improves recovery from aphasia, when
      compared with right hemisphere participation. TS has been applied to stimulate
      the activity of the left hemisphere or to inhibit homotopic areas in the right
      hemisphere. Various factors can interfere with the brain's response to TS,
      including the size and location of the lesion, the time elapsed since the causal
      event, and individual differences in the hemispheric language dominance pattern.
      The following questions are discussed in the present article: [a] Is inhibition
      of the right hemisphere truly beneficial?;[b] Is the transference of the language
      network to the left hemisphere truly desirable in all patients?;[c] Is the use of
      TS during the post-stroke subacute phase truly appropriate? Different patterns of
      neuroplasticity must occur in post-stroke aphasia.

PMID- 29213907
TI  - Cross-cultural adaptation process of the "Conversation Analysis Profile for
      People with Aphasia" to the Portuguese language.
AB  - : The Conversation Analysis Profile for People with Aphasia (CAPPA) provides
      specific information about strengths and weaknesses of the communication between
      people with aphasia and their family caregiver within a conversational context.
      Objective: The aim of this paper was to present the results of the first stages
      of cross-cultural adaptation of the CAPPA for the European Portuguese language.
      Methods: This methodology study describes the translation and back-translation
      processes, following the recommended steps to that end. In addition, following
      the consent of one of the original authors, the process of content validation of
      the CAPPA commenced. The instrument was submitted for assessment before a panel
      of experts in the area, who constituted the population of this study. Results:
      After the translation and back-translation processes, a panel of experts was
      convened to adapt the Delphi technique. Some questions were excluded on the basis
      of ambiguity, relevance and potential repetition. Suggestions made by the expert
      panel were included in a revised version of the tool. 159 items obtained a 100%
      consensus in relevance, and 157 items were considered suitable by the expert
      panel, validating the content of the instrument. Conclusion: The final version
      will now be applied to the target population in order to carry out the
      psychometric validation.

PMID- 29213908
TI  - Automatic classification of written descriptions by healthy adults: An overview
      of the application of natural language processing and machine learning techniques
      to clinical discourse analysis.
AB  - : Discourse production is an important aspect in the evaluation of brain-injured
      individuals. We believe that studies comparing the performance of brain-injured
      subjects with that of healthy controls must use groups with compatible education.
      A pioneering application of machine learning methods using Brazilian Portuguese
      for clinical purposes is described, highlighting education as an important
      variable in the Brazilian scenario. Objective: The aims were to describe how
      to:(i) develop machine learning classifiers using features generated by natural
      language processing tools to distinguish descriptions produced by healthy
      individuals into classes based on their years of education; and(ii) automatically
      identify the features that best distinguish the groups. Methods: The approach
      proposed here extracts linguistic features automatically from the written
      descriptions with the aid of two Natural Language Processing tools: Coh-Metrix
      Port and AIC. It also includes nine task-specific features (three new ones, two
      extracted manually, besides description time; type of scene described - simple or
      complex; presentation order - which type of picture was described first; and
      age). In this study, the descriptions by 144 of the subjects studied in Toledo18
      were used,which included 200 healthy Brazilians of both genders. Results and
      Conclusion: A Support Vector Machine (SVM) with a radial basis function (RBF)
      kernel is the most recommended approach for the binary classification of our
      data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a
      strong candidate to replace manual feature selection methods.

PMID- 29213909
TI  - Acquired dysgraphia in adults following right or left-hemisphere stroke.
AB  - Objective: This study aimed to assess the strengths and difficulties in word and
      pseudoword writing in adults with left- and right-hemisphere strokes, and discuss
      the profiles of acquired dysgraphia in these individuals. Methods: The profiles
      of six adults with acquired dysgraphia in left- or right-hemisphere strokes were
      investigated by comparing their performance on word and pseudoword writing tasks
      against that of neurologically healthy adults. A case series analysis was
      performed on the patients whose impairments on the task were indicative of
      acquired dysgraphia. Results: Two patients were diagnosed with lexical dysgraphia
      (one with left hemisphere damage, and the other with right hemisphere damage),
      one with phonological dysgraphia, another patient with peripheral dysgraphia, one
      patient with mixed dysgraphia and the last with dysgraphia due to damage to the
      graphemic buffer. The latter patients all had left-hemisphere damage (LHD). The
      patterns of impairment observed in each patient were discussed based on the dual
      route model of writing. Conclusion: The fact that most patients had LHD rather
      than right-hemisphere damage (RHD) highlights the importance of the former
      structure for word processing. However, the fact that lexical dysgraphia was also
      diagnosed in a patient with RHD suggests that these individuals may develop
      writing impairments due to damage to the lexical route, leading to heavier
      reliance on phonological processing. Our results are of significant importance to
      the planning of writing interventions in neuropsychology.

PMID- 29213910
TI  - Inferential abilities based on pictorial stimuli in patients with right
      hemisphere damage: influence of schooling.
AB  - : Inferences are mental representations, formed through the interaction between
      explicit linguistic information and an individual's world knowledge. It is well
      known that individuals with brain damage in the right hemisphere (RH) often fail
      on this task and that schooling may be a variable affecting this. Objective: To
      compare the effect of schooling on an inference comprehension task based on
      pictorial stimuli in patients with RH lesion. Methods: The inferential abilities
      of 75 controls and 50 patients with RH lesion were assessed through the pictorial
      stimuli from the instrument "300 exercises of comprehension of logical and
      pragmatic inferences and causal chains". Both groups were stratified into two
      subgroups according to schooling level: 4 to 8 years and 9 or more years. Results
      and Conclusion: Highly educated subjects performed better than low educated
      individuals, both on intergroup and intragroup comparisons (p<0.0001) for logical
      and pragmatic inference ability.

PMID- 29213911
TI  - Age of acquisition and naming performance in Frisian-Dutch bilingual speakers
      with dementia.
AB  - : Age of acquisition (AoA) of words is a recognised variable affecting language
      processing in speakers with and without language disorders. For bi- and
      multilingual speakers their languages can be differentially affected in
      neurological illness. Study of language loss in bilingual speakers with dementia
      has been relatively neglected. Objective: We investigated whether AoA of words
      was associated with level of naming impairment in bilingual speakers with
      probable Alzheimer's dementia within and across their languages. Methods: Twenty
      six Frisian-Dutch bilinguals with mild to moderate dementia named 90 pictures in
      each language, employing items with rated AoA and other word variable measures
      matched across languages. Quantitative (totals correct) and qualitative (error
      types and (in)appropriate switching) aspects were measured. Results: Impaired
      retrieval occurred in Frisian (Language 1) and Dutch (Language 2), with a
      significant effect of AoA on naming in both languages. Earlier acquired words
      were better preserved and retrieved. Performance was identical across languages,
      but better in Dutch when controlling for covariates. However, participants
      demonstrated more inappropriate code switching within the Frisian test setting.
      On qualitative analysis, no differences in overall error distribution were found
      between languages for early or late acquired words. There existed a significantly
      higher percentage of semantically than visually-related errors. Conclusion: These
      findings have implications for understanding problems in lexical retrieval among
      bilingual individuals with dementia and its relation to decline in other
      cognitive functions which may play a role in inappropriate code switching. We
      discuss the findings in the light of the close relationship between Frisian and
      Dutch and the pattern of usage across the life-span.

PMID- 29213912
TI  - Analysis of word number and content in discourse of patients with mild to
      moderate Alzheimer's disease.
AB  - : Alzheimer's disease (AD) is characterized by impairments in memory and other
      cognitive functions such as language, which can be affected in all aspects
      including discourse. A picture description task is considered an effective way of
      obtaining a discourse sample whose key feature is the ability to retrieve
      appropriate lexical items. There is no consensus on findings showing that
      performance in content processing of spoken discourse deteriorates from the
      mildest phase of AD. Objective: To compare the quantity and quality of discourse
      among patients with mild to moderate AD and controls. Methods: A cross-sectional
      study was designed. Subjects aged 50 years and older of both sexes, with one year
      or more of education, were divided into three groups: control (CG), mild AD
      (ADG1) and moderate AD (ADG2). Participants were asked to describe the "cookie
      theft" picture. The total number of complete words spoken and information units
      (IU) were included in the analysis. Results: There was no significant difference
      among groups in terms of age, schooling and sex. For number of words spoken, the
      CG performed significantly better than both the ADG 1 and ADG2, but no difference
      between the two latter groups was found. CG produced almost twice as many
      information units as the ADG1 and more than double that of the ADG2. Moreover,
      ADG2 patients had worse performance on IUs compared to the ADG1. Conclusion:
      Decreased performance in quantity and content of discourse was evident in
      patients with AD from the mildest phase, but only content (IU) continued to
      worsen with disease progression.

PMID- 29213913
TI  - Rehabilitation of lexical and semantic communicative impairments: An overview of
      available approaches.
AB  - : Lexical-semantic impairments are common consequences of acquired neurological
      damage. However, little is known about the benefits of existing treatment methods
      for this type of language impairment. Objective: To evaluate current research
      into lexical-semantic interventions for adults with dementia, TBI or stroke.
      Methods: The PubMed, PsycInfo and SCOPUS databases were searched for studies
      related to rehabilitation, neurological conditions, communicative and lexical
      semantic skills published between 2004 and 2014. Results: Twenty-eight of the 453
      abstracts found were selected for the review based on the PRISMA method. Most of
      the studies described treatments for anomia. Semantic tasks were the most
      commonly used, followed by phonological and gestural strategies. Interventions
      were individual and involved formal tasks, although the number, frequency and
      duration of sessions varied between studies. Conclusion: Although lexical
      semantic interventions lead to improvements in language abilities, they are still
      poorly described in the literature, and must be further investigated in terms of
      their efficacy, effectiveness and long-term effects.

PMID- 29213914
TI  - Discourse intervention strategies in Alzheimer's disease: Eye-tracking and the
      effect of visual cues in conversation.
AB  - Objective: The goal of this study was to investigate whether on-topic visual cues
      can serve as aids for the maintenance of discourse coherence and informativeness
      in autobiographical narratives of persons with Alzheimer's disease (AD). Methods:
      The experiment consisted of three randomized conversation conditions: one without
      prompts, showing a blank computer screen; an on-topic condition, showing a
      picture and a sentence about the conversation; and an off-topic condition,
      showing a picture and a sentence which were unrelated to the conversation. Speech
      was recorded while visual attention was examined using eye tracking to measure
      how long participants looked at cues and the face of the listener. Results:
      Results suggest that interventions using visual cues in the form of images and
      written information are useful to improve discourse informativeness in AD.
      Conclusion: This study demonstrated the potential of using images and short
      written messages as means of compensating for the cognitive deficits which
      underlie uninformative discourse in AD. Future studies should further investigate
      the efficacy of language interventions based in the use of these compensation
      strategies for AD patients and their family members and friends.

PMID- 29213915
TI  - Interdisciplinary Therapy for patients with dementia.
AB  - : Patients with dementia require rehabilitation involving several health
      professionals, where interdisciplinary care can further enhance the routine of
      patients and their families. Objective: To compare the functional performance of
      elderly with dementia before and after an interdisciplinary intervention program
      provided by a healthcare service of medium complexity. Methods: Three cases with
      clinically-confirmed dementia enrolled on an interdisciplinary rehabilitation
      program were reported. The following instruments were applied: Mini Mental-State
      Exam, Clinical Dementia Rating, Geriatric Depression Scale, Lawton & Brody Index,
      and the Functional Independence Measure for adults (FIM). The therapeutic
      strategies were individualized and designed based on patient performance on the
      FIM, according to the criteria of the Classification of Functionality, Disability
      and Health, implemented at the house of therapy of the Center for Integrated
      Rehabilitation together with provision of guidance. Results: A reduction in
      functional dependence was observed after intervention, evidenced by less
      supervision needed to carry out Activities of Daily Living. Conclusion: The three
      patients benefited from the interdisciplinary intervention.

PMID- 29213916
TI  - Brief intervention for agrammatism in Primary Progressive Nonfluent Aphasia: A
      case report.
AB  - The non-fluent and agrammatic variant of Primary Progressive Aphasia (NFPPA) is
      characterized by reduced verbal production with deficits in building
      grammatically correct sentences, involving dysfunctions in syntactic and
      morphological levels of language. There are a growing number of studies about non
      pharmacological alternatives focusing on the rehabilitation of functional aspects
      or specific cognitive impairments of each variant of PPA. This study reports a
      short-term treatment administered to a patient with NFPPA focusing on the
      production of sentences. The patient had significant reduction in verbal fluency,
      use of keywords, phrasal and grammatical simplifying as well as anomia. Using the
      method of errorless learning, six sessions were structured to stimulate the
      formation of sentences in the present and past with the cloze technique. The
      patient had improvement restricted to the strategy, with 100% accuracy on the
      trained phrases and generalization to untrained similar syntactic structure after
      training. These results persisted one month after the treatment.

PMID- 29213917
TI  - Sentence production in rehabilitation of agrammatism: A case study.
AB  - Agrammatism is characterized by morphosyntactic deficits in production of
      sentences. Studies dealing with the treatment of these deficits are scarce and
      their results controversial. The present study describes the rehabilitation of a
      case diagnosed as chronic Broca's aphasia, with agrammatism, using a method
      directed to sentence structural deficits. The method aims to expand the
      grammatical repertoire by training production of sentences with support from
      contexts that stimulate actions and dialogues. The patient showed positive
      results on all types of sentences trained and generalized the gains to
      spontaneous speech. However, these benefits were not sustained in the long term.

PMID- 29213919
TI  - It is time to focus on an underestimated epidemic.

PMID- 29213918
TI  - Logopenic aphasia or Alzheimer's disease: Different phases of the same disease?
AB  - The logopenic variant of Primary Progressive Aphasia, or logopenic aphasia, is a
      the most recently described variant of Primary Progressive Aphasia and also the
      least well defined. This variant can present clinical findings that are also
      common to Alzheimer's disease, given they both share the same cytopathologic
      findings. This article reports the clinical case of a patient for whom it proved
      difficult to define a clinical diagnosis, being split between the logopenic
      variant and Alzheimer's disease at different phases of the disease. Using this
      case as an example and drawing on the latest evidence from the literature on the
      logopenic variant, we postulate the hypothesis that this variant may present as
      an initial symptom of Alzheimer's disease in some atypical cases.

PMID- 29213920
TI  - An update on aging and dementia in Chile.
AB  - Chile is in an advanced demographic transition stage with the population over 60
      years of age representing 15% of the total population and whose number of elderly
      has more than doubled between 1990 and 2014. Rapid economic advancement has
      promoted significant changes in social organization to which the country is not
      accustomed. The mental health problems of the elderly are particularly
      challenging to the country's present social and health structures. The prevalence
      of dementia in people over 60 years exceeds 8% and is even higher in the rural
      population. There is more training on dementia in the local medical and
      scientific community, increased awareness within the civilian community but
      insufficient responsiveness from the state to the broad diagnostic and
      therapeutic requirements of patients and caregivers. The objective of the present
      study was to provide an update of the information on dementia in the context of
      the ageing process in Chile.

PMID- 29213921
TI  - Prevalence of dementia in Colombian populations.
AB  - With the gradual increase in the life expectancy of the population due to
      scientific progress and public health at the service of society, the prevalence
      of dementia has been increasing at different rates worldwide. Currently, the
      prevalence rates range between 5% and 7% (6.4% in the U.S. and up to 8.5 % in
      Latin America) in subjects older than 60 years. The lowest prevalence rate (2.1%)
      has been reported from sub-Saharan Africa, probably due to selective mortality
      under 60 years of age. By contrast, a very high prevalence of dementia (23.6%
      dementia in individuals >60 years) was observed in the city of Neiva, Southern
      Colombia. We believe that this high rate could be explained by the presence of
      several risk factors such as very low schooling, low socio-economic strata,
      chronic diseases, the inclusion of geriatric homes among others, and additional
      unknown factors.

PMID- 29213922
TI  - Trinidad and Tobago: A decade of dementia research.
AB  - In 2003, academic staff members at The University of the West Indies Faculty of
      Medical Sciences St Augustine Trinidad and Tobago combined their expertise to
      make strides in Alzheimer's and Dementia research in Trinidad and Tobago. Dr.
      Nelleen Baboolal, Dr. Gershwin Davis and Professor Amanda McRae began developing
      a project that has produced significant results by examining not only the
      epidemiology of dementia, but the associated risk factors; caregiver burden and
      ultimately establishing biomarkers for the disease. This review is an account of
      our results from a decade of dementia research and how they are contributing
      toward mitigating the dementia tsunami in Trinidad and Tobago.

PMID- 29213923
TI  - A population-based study of cognitive impairment in socially vulnerable adults in
      Argentina. The Matanza Riachuelo study preliminary results.
AB  - : Population aging has taken place intensively worldwide, even in developing
      countries. These countries have population groups with low resources and basic
      unmet needs that are frequently omitted from epidemiological studies. Objective:
      The purpose of this study was to determine the prevalence of cognitive impairment
      (CI) and dementia in an economic and socially vulnerable population from
      Argentina. Methods: A door-to-door observational population-based survey among
      adults over 60 years of cognitive impairment and dementia in the social
      vulnerable area of the Matanza Riachuelo Basin, in the suburban area of Buenos
      Aires, Argentina was conducted. Trained psychologists interviewed subjects and a
      proxy informant. A standardized protocol including a socio-demographic
      questionnaire, the Mini-Mental State Examination, the Geriatric Depression Scale
      and a functional inventory for IADL and ADL was administered. Diagnoses were
      divided into three general categories: normal cognitive function, cognitive
      impairment-no dementia (CIND) and dementia. Results and Conclusions: A total of
      2437 elderly persons were assessed, of which 73.6% fulfilled inclusion criteria.
      The prevalence of CI among those over 60 was 26.4% (18.1% CIND and 8.3% dementia)
      with higher prevalence of dementia in younger individuals than rates reported in
      developed counties, probably due to low control of vascular risk factors. This
      information can help inform health public decisions in the generation of programs
      and plans for the prevention, diagnosis and treatment of cognitive impairment in
      this type of socially vulnerable population.

PMID- 29213924
TI  - Cognitive impairment in individuals with low educational level and homogeneous
      sociocultural background.
AB  - : Prevalence studies of dementia and cognitive impairment in different cultures
      and environments are necessary. Objective: To verify the prevalence of cognitive
      impairment and dementia in a rural homogeneous population from flooded areas in
      the Amazonian Basin. Methods: A total of 163 subjects were interviewed with
      neurological, cognitive and functional evaluation. The individuals were
      classified as demented or cognitive impairment no dementia (CIND). Results:
      cognitive impairment was observed in 11.4% (n=18 individuals). Ten out of the 18
      were diagnosed as CIND and eight with dementia. The prevalence rate of dementia
      was 4.9% in subjects aged 50 years or over and of CIND was 6.1%. Considering only
      the elder group (>64 years of age), there was a 12.3% prevalence of dementia and
      7.7% of CIND. Conclusion: In a homogeneous population, we observed a similar
      prevalence of dementia to rates reported by studies in Brazil and in other
      developed and developing countries.

PMID- 29213925
TI  - The Leganes cognitive test correlates poorly with MRI evidence of global cortical
      atrophy in an underserved community: A population-based and nested case-control
      study in rural Ecuador (The Atahualpa Project).
AB  - Objective: We aimed to evaluate whether the Leganes cognitive test (LCT)
      correlates with global cortical atrophy (GCA) and can be used as a surrogate for
      structural brain damage. Methods: Atahualpa residents aged > 60 years identified
      during a door-to-door survey underwent MRI for grading GCA. Using multivariate
      generalized linear models, we evaluated whether continuous LCT scores correlated
      with GCA, after adjusting for demographics, education, cardiovascular health
      (CVH) status, depression and edentulism. In a nested case-control study, GCA
      severity was assessed in subjects with LCT scores below the cutoff level for
      dementia (< 22 points) and in matched controls without dementia. Results: Out of
      311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2+/-7.5 years,
      59% were women, 83% had primary school education, 73% had poor CVH status, 12%
      had symptoms of depression and 43% had edentulism. Average LCT score was 26.7+/
      3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in
      95, and severe in 26 individuals. On the multivariate model, mean LCT score was
      not associated with GCA severity (beta=0.06, SE=0.34, p=0.853). Severe GCA was
      noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14
      2.81, p=0.752, McNemar's test). Conclusion: The LCT does not correlate with
      severity of GCA after adjusting for potential confounding variables, and should
      not be used as a reliable estimate of structural brain damage.

PMID- 29213926
TI  - Incidence of dementia and association with APOE genotype in older Cubans.
AB  - Objective: In an admixed population of older Cubans, the incidence and
      association of APOE and sociodemographic risk factors with dementia incidence was
      estimated. Methods: A single-phase survey (baseline) of all over 65-year-olds
      residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and
      2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria.
      APOE genotype was determined in 2520 participants. An incidence wave was
      conducted 4.5 years after cohort inception in order to estimate incidence and
      associations with sociodemographic risk factors of the APOE epsilon4 genotype.
      Results: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95%
      CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6
      23.5). Older age, a family history of dementia and APOE epsilon4 genotype were
      independent risk factors for incident 10/66 dementia. APOE genotype was
      associated cross-sectionally with dementia prevalence, but the effect on the
      incidence of dementia was attenuated, and only apparent among those in the
      youngest age group. Conclusion: The incidence of dementia in the older Cuban
      population is relatively high and similar to levels reported in Europe and North
      America. The study showed that the relationship between APOE epsilon4 and
      incident dementia is stronger in the younger-old than the older-old and that this
      change must be taken into account in models of dementia.

PMID- 29213927
TI  - Cognitive impairment and risk factor prevalence in a population over 60 in
      Argentina.
AB  - : Epidemiological data on dementia and cognitive impairment are scarce in South
      America. In Argentina, no dementia/cognitive impairment population-based
      epidemiological studies are available. The Ceibo Study is a population-based
      epidemiological study of dementia and cognitive impairment in individuals over 60
      to be conducted. The present paper reports the results of the pilot phase (survey
      of cognitive impairment) conducted in Canuelas (province of Buenos Aires).
      Methods: In a door-to-door survey, trained high school students evaluated 1453
      individuals aged 60 years and over in one day using a demographic data and risk
      factors questionnaire, the Mini-Mental State Examination (MMSE) and the 15-item
      Geriatric Depression Scale (GDS). Results: Mean age of the individuals was 70.9
      (+/-7.5) years, 61.4% were women, mean schooling was 5.5 (+/-3.5) years. Mean
      MMSE score was 24.5 (+/-4.7) and mean GDS 3.1 (+/-2.7). Risk factors of higher
      prevalence in the population under study were: hypertension (40.6%), smoking
      (35.1%), alcohol consumption (32.8%), high cholesterol (16.1%), diabetes (12.5%),
      cranial trauma with loss of consciousness (12.5%), 7 points or more on the GDS
      (11.7%). Prevalence of cognitive impairment for the whole sample was 23%, and
      16.9% in subjects aged 60-69, 23.3% in 70-79 and 42.5% in subjects aged 80 or
      over . A significant correlation of cognitive impairment with age, functional
      illiteracy, cranial trauma, high blood pressure, inactivity and depression was
      found. Conclusion: In this pilot study, the prevalence of cognitive impairment
      was comparable with previous international studies.

PMID- 29213928
TI  - Memory clinic experience under a social security health system in Costa Rica.
AB  - : Dementia and mild cognitive impairment (MCI) are an increasingly prevalent
      clinical entity in our field, showing an increasing incidence with age.
      Objective: The purpose of this study was to identify the main types of dementia
      and MCI treated in a memory disorders unit in Costa Rica. Methods: A consecutive
      and standardized register of patients diagnosed with dementia and MCI at the
      memory disorders unit of the National Geriatrics and Gerontology Hospital (NGGH)
      was analyzed. Results: Dementia was diagnosed in 63.5% of the 3572 cases, whereas
      10.6% met criteria for MCI. The most frequent type of dementia was Alzheimer's
      disease (47.1%), followed by vascular pathology (28.9%), mixed forms (17.2%) and
      other types (6.8%). In MCI, 69.5% were of amnestic multiple domain type and 14.3%
      were non-amnestic multiple domain, while 41.3% were of vascular and 35.8% of
      neurodegenerative etiology. Mean age was 79.6+/-6.7 years and 64.7% were women in
      dementia cases whereas mean age was 76.4+/-6.9 years and 62.1% were women in MCI.
      Mean years of schooling was 4.95+/-4.09 years and 6.87+/-4.71, while mean time
      between onset of symptoms and clinical diagnosis was 3.2+/-2.6 years and 2.67+/
      2.69 years, in dementia and MCI, respectively. Conclusion: The determination of
      the main types of dementia and MCI in Costa Rica and their main features has
      allowed the registration of comprehensive, hitherto unavailable information that
      will be useful for the management and strategic planning of public health care.

PMID- 29213929
TI  - Informal caregiver burden in middle-income countries: Results from Memory Centers
      in Lima - Peru.
AB  - Objective: The aim of this study was to evaluate caregiver burden based on Zarit
      Burden Interview (ZBI) and depression in caregivers on the Beck Depression
      Inventory-II (BDI-II). Methods: Literate individuals, 18 years or older, who
      spoke Spanish as their native language were included. Demographic
      characteristics: Age, sex, education, relationship to person with dementia,
      length of time caregiving, other sources of help for caring, impact on the
      household economy, family support, and perception of impaired health; and
      Clinical data on care-recipients: type of dementia, time since diagnosis,
      treatment, and Global Deterioration Scale (GDS); the ZBI and BDI-II. Descriptive
      and analytical statistics were employed to assess caregiver burden and predictors
      of higher burden in caregivers. Results: A total of 92 informal caregivers were
      evaluated. Regarding care-recipients, 75% were 69 years old or over, 75% had at
      least one year since diagnosis, 73.9% had Alzheimer's disease, 84.8% received
      treatment, 75% scored 5 or over on the GDS. For caregivers, 75% were 55.5 years
      old or over, predominantly female (81.5%), married (83.7%), the spouse of care
      recipients (60.87%), had at least 10 years of education (75.0%) and one year of
      caregiving (75%), reduced entertainment time (90.2%) and self-perception of
      impaired health (83.7%). Median score on the ZBI was 37.5 (minimum value = 3; and
      maximum value = 74). The coefficient of BDI was 1.38 (p-value <0.001).
      Conclusion: This sample of Peruvian informal caregivers showed elevated ZBI
      values. Self-perception of worsened health, repercussion on the family economy
      and time caregiving were the main determinants of ZBI, although only BDI was a
      consistent predictor of ZBI.

PMID- 29213930
TI  - Burden, anxiety and depression in caregivers of Alzheimer patients in the
      Dominican Republic.
AB  - : Alzheimer's disease (AD) has a major impact by limiting the ability to live
      independently. This condition of dependency involves all members of the family,
      particularly those who take direct care of patients. The changes that take place
      in caregivers' lives may alter their health and have an effect on the care of the
      sick. Objective: To determine the presence of burden, anxiety and depression in
      caregivers of Alzheimer's patients. Method: A descriptive cross-sectional study
      was performed in 67 family caregivers from the Alzheimer's Clinic Research Unit,
      Memory and Alzheimer, in the city of Santiago, Dominican Republic. Caregivers
      were evaluated for burden intensity with the Zarit scale and for both depression
      and anxiety using the respective Hamilton scales. Descriptive statistical
      analysis and Pearson correlation were used. Results: 84% of caregivers were
      female, and 52% were older than 50 years. A total of 36% exhibited caregiver
      burden; 19% anxiety symptoms; and 43% depressive symptoms. No statistical
      significance was found between age, sex and number of hours of care. A
      significant association was found in the Pearson correlation coefficient between
      caregiver burden, anxiety and depression. Conclusion: Caregiver burden was
      associated with anxiety and depression. It is important for health professionals
      to include caregiver assessments in the treatment protocols of dementia. Policy
      should include support programs for carers.

PMID- 29213931
TI  - Performance of the Visual Analogue Scale of Happiness and of the Cornell Scale
      for Depression in Dementia in the Tremembe Epidemiological Study, Brazil.
AB  - : Depression is a major growing public health problem. Many population studies
      have found a significant relationship between depression and the presence of
      cognitive disorders. Objective: To establish the correlation between the Visual
      Analogue Scale of Happiness and the Cornell Scale for Depression in Dementia in
      the population aged 60 years or over in the city of Tremembe, state of Sao Paulo,
      Brazil. Methods: An epidemiological survey involving home visits was carried out
      in the city of Tremembe. The sample was randomly selected by drawing 20% of the
      population aged 60 years or older from each of the city's census sectors. In this
      single-phase study, the assessment included clinical history, physical and
      neurological examination, cognitive evaluation, and application of both the
      Cornell Scale and the Analogue Scale of Happiness for psychiatric symptoms. The
      presence of depressive symptoms was defined as scores greater than or equal to 8
      points on the Cornell Scale. Results: A total of 623 subjects were evaluated and
      of these 251 (40.3%) had clinically significant depressive symptoms on the
      Cornell Scale, with a significant association with female gender (p<0.001) and
      with lower education (p=0.012). One hundred and thirty-six participants (21.8%)
      chose the unhappiness faces, with a significant association with age (p<0.001),
      female gender (p=0.020) and low socioeconomic status (p=0.012). Although there
      was a statistically significant association on the correlation test, the
      correlation was not high (rho=0.47). Conclusion: The prevalence of depressive
      symptoms was high in this sample and the Visual Analogue Scale of Happiness and
      Cornell Scale for Depression in Dementia should not be used as similar
      alternatives for evaluating the presence of depressive symptoms, at least in
      populations with low educational level.

PMID- 29213934
TI  - In the March 2015 issue.

PMID- 29213932
TI  - Brazilian research on cognitive impairment and dementia from 1999 to 2013.
AB  - : The phenomenon of demographic transition in recent decades has increased the
      number of elderly people in Brazil, promoting an escalation in chronic
      degenerative conditions, particularly dementia and cognitive related disorders.
      Objective: The aim of this study was to assess the evolution of the Brazilian
      scientific publications on dementia and related conditions from 1999 to 2013.
      Methods: Articles published during the analysis period were searched on three
      electronic databases: Scopus, Medline (via PubMed) and Lilacs (via BVS). The
      keywords used were Alzheimer's disease, dementia and mild cognitive impairment,
      with Brazil as the country of affiliation. Results: A total of 1,657 articles met
      the conditions for inclusion in the study. The output of Brazilian researchers in
      the area of cognitive disorders increased 11.38-fold in the fifteen-year period
      of analysis and 4.98-fold from 2003 to 2013. More than half of the articles (53%)
      were published in international journals. The majority of institutions involved
      in publications were public universities while 19% were collaborative studies
      involving Brazilian and international institutions. Conclusion: Despite marked
      growth, the number of Brazilian scientific publications in the area of cognitive
      impairment and dementia is still low. More effort is required to improve the
      output of Brazilian researchers and institutions. Possible strategies to
      accomplish this increase could be to encourage residents to participate in
      publications of scientific papers during their residence program and to increase
      the collaborations between different institutions within Brazil and with the
      international scientific community.

PMID- 29213935
TI  - Argyrophilic grain disease: An underestimated tauopathy.
AB  - Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly
      frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians.
      The most common AGD manifestation is slowly progressive amnestic mild cognitive
      impairment, accompanied by a high prevalence of neuropsychiatric symptoms. AGD
      diagnosis can only be achieved postmortem based on the finding of its three main
      pathologic features: argyrophilic grains, oligodendrocytic coiled bodies and
      neuronal pretangles. AGD is frequently seen together with Alzheimer's disease
      type pathology or in association with other neurodegenerative diseases. Recent
      studies suggest that AGD may be a defense mechanism against the spread of other
      neuropathological entities, particularly Alzheimer's disease. This review aims to
      provide an in-depth overview of the current understanding on AGD.

PMID- 29213936
TI  - Obstructive sleep apnea and neurodegenerative diseases: A bidirectional relation.
AB  - Sleep disorders are common during the clinical course of the main
      neurodegenerative diseases. Among these disorders, obstructive sleep apnea has
      been extensively studied in the last decade and recent knowledge regarding its
      relationship with the neurodegenerative process points a bidirectional
      relationship. Neurodegenerative diseases can lead to functional changes in the
      respiratory system that facilitate the emergence of apnea. On the other hand,
      obstructive sleep apnea itself can lead to acceleration of neuronal death due to
      intermittent hypoxia. Considering that obstructive sleep apnea is a potentially
      treatable condition, its early identification and intervention could have a
      positive impact on the management of patients with neurodegenerative diseases.

PMID- 29213937
TI  - Synesthesia and music perception.
AB  - The present review examined the cross-modal association of sensations and their
      relationship to musical perception. Initially, the study focuses on synesthesia,
      its definition, incidence, forms, and genetic and developmental factors. The
      theories of the neural basis of synesthesia were also addressed by comparing
      theories emphasizing the anatomical aspect against others reinforcing the
      importance of physiological processes. Secondly, cross-modal sensory
      associations, their role in perception, and relationship to synesthesia were
      analyzed. We propose the existence of a lower, unconscious degree of synesthesia
      in non-synesthetes. This latent synesthesia (without explicit sensory
      manifestations) would be functional, aiding the construction of abstract
      associations between different perceptual fields. Musical meaning might be
      constructed largely by synesthetic processes, where the sensory associations from
      sound activate memories, images, and emotions.

PMID- 29213938
TI  - The effect of deep brain stimulation on motor and cognitive symptoms of
      Parkinson's disease: A literature review.
AB  - : Deep brain stimulator (DBS) implant surgery is considered a breakthrough in the
      treatment of Parkinson's disease, especially in cases where motor symptoms cannot
      be controlled through conventional drug treatment. Its benefits have been studied
      extensively in the literature, particularly in relation to motor symptoms.
      However, the disease's cognitive aspects have been studied to a lesser extent.
      Objective: This systematic review aims to assess the effects of DBS surgery on
      motor and cognitive symptoms in patients with Parkinson's disease. Methods: The
      search strategy included MEDLINE, LILACs, SCIELO and the Cochrane Library.
      Randomized clinical trials with DBS surgical intervention and Parkinson's disease
      were included. Of the 178 studies identified, 19 met the eligibility criteria.
      These studies were descriptively analyzed as regards to their results. Results:
      Control of motor symptoms, as assessed by the UPDRS Part III scale, was found in
      all of the studies, pointing to great interest in this outcome and demonstrating
      an advantage of DBS over conventional drug treatment. Regarding cognitive
      aspects, heterogeneity in the choice of subjects studied and the use of different
      assessment tools for each was evident, hampering comparisons and leading to
      inconclusive results. Conclusion: This review provides a broad overview of the
      effects of DBS on Parkinson's disease symptoms. However, it is suggested that
      future studies be conducted to establish a gold-standard protocol for
      neuropsychological assessment, thereby enabling data comparison and more
      consistent conclusions.

PMID- 29213939
TI  - Cost-of-illness study in a retrospective cohort of patients with dementia in
      Lima, Peru.
AB  - : Dementia is a major cause of dependency and disability among older persons, and
      imposes huge economic burdens. Only a few cost-of-illness studies for dementia
      have been carried out in middle and low-income countries. Objective: The aim of
      this study was to analyze costs of dementia in demented patients of a private
      clinic in Lima, Peru. Methods: We performed a retrospective, cohort, 3-month
      study by extracting information from medical records of demented patients to
      assess the use of both healthcare and non-healthcare resources. The total costs
      of the disease were broken down into direct (medical and social care costs) and
      indirect costs (informal care costs). Results: In 136 outpatients, we observed
      that while half of non-demented patients had total care costs of less than US$ 23
      over three months, demented patients had costs of US$ 1500 or over (and more than
      US$ 1860 for frontotemporal dementia). In our study, the monthly cost of a
      demented patient (US$ 570) was 2.5 times higher than the minimum wage (legal
      minimum monthly wage in Peru for 2011: US$ 222.22). Conclusion: Dementia
      constitutes a socioeconomic problem even in developing countries, since patients
      involve high healthcare and non-healthcare costs, with the costs being especially
      high for the patient's family.

PMID- 29213940
TI  - Indirect cost with dementia: A Brazilian study.
AB  - : Costs with dementia have been the focus of research around the world and
      indirect costs to the caregiver appear in the literature as responsible for the
      greatest impact. In Latin American (LA) studies, indirect costs with dementia
      range from 60% to 75% of family income. Objective: To present preliminary results
      of the study "Description of the methods and cost analysis with dementia"
      currently being conducted at the Behavioral and Cognitive Neurology Unit of
      Hospital de Clinicas of University of Sao Paulo - HC-FMUSP. Methods: A cross
      sectional study which, to date, includes interviews of 93 primary caregivers. The
      research protocol includes a sociodemographic questionnaire, the Functional
      Assessment Staging (FAST) scale, the Burden Interview (Zarit), an economic
      classification scale, and the Resource Utilization in Dementia (RUD) scale.
      Results: Monthly indirect costs were US$ 1,122.40, US$ 1,508.90 and US$ 1,644.70
      stratified into mild, moderate and severe dementia, respectively. The projected
      annual indirect costs were US$ 13,468.80, US$ 18,106.80 and US$ 19,736.40,
      representing 69 to 169% of family income. Conclusion: This small sample showed
      that the impact of indirect costs with dementia in Brazil may be higher than that
      reported in other Latin American (LA) studies. These initial results may
      represent an important contribution for further research on costs with dementia
      in LA.

PMID- 29213941
TI  - Subjective memory complaints associated with depression and cognitive impairment
      in the elderly: A systematic review.
AB  - : The aging process can be accompanied by a slight decline in cognitive
      functioning, and subjective memory complaints (SMC) appear to be common in the
      elderly population. Objective: To determine whether SMC is associated with
      cognitive loss or depression and can predict dementia. Methods: A systematic
      review of the literature was conducted. Articles were selected on the following
      databases, LILACS, SCOPUS, SCiELO, PubMed and Web of Science from August to
      October 2013. Article selection was based on inclusion and exclusion criteria.
      Studies published between 2010 and 2013, written in English, Spanish or
      Portuguese, involving populations 65 years or older, were included. Reviews were
      excluded. Results: After the selection, a summary of the 20 articles retrieved
      was carried out. Of the total articles retrieved, fifteen were cross-sectional
      studies and five were longitudinal studies. Most of the cross-sectional studies
      associated SMC with depression, objective cognitive impairment and anxiety. The
      emergence of dementia in people with SMC was evidenced in longitudinal studies.
      Albeit less frequently, SMC were also associated with reduced quality of life,
      impairment in Activities of Daily Living (ADL), emergence of neuropsychiatric
      symptoms, lower hippocampal volume, amygdala volume reduction, increased
      activation of the left temporal, bilateral thalamus, caudate and posterior
      cingulate, and with the occurrence of ApoE epsilon4. Conclusion: SMC may be
      associated with changes in mood and/or cognition, and its occurrence appears to
      increase the likelihood of dementia. In order to further our understanding of the
      topic, future studies should consider the recruitment of representative samples
      with control groups and longitudinal designs.

PMID- 29213942
TI  - Relationships between episodic memory performance prediction and sociodemographic
      variables among healthy older adults.
AB  - : Previous studies have suggested that performance prediction, an aspect of
      metamemory, may be associated with objective performance on memory tasks.
      Objective: The objective of the study was to describe memory prediction before
      performing an episodic memory task, in community-dwelling older adults,
      stratified by sex, age group and educational level. Additionally, the association
      between predicted and objective performance on a memory task was investigated.
      Methods: The study was based on data from 359 participants in the FIBRA study
      carried out at Ermelino Matarazzo, Sao Paulo. Memory prediction was assessed by
      posing the question: "If someone showed you a sheet with drawings of 10 pictures
      to observe for 30 seconds, how many pictures do you think you could remember
      without seeing the sheet?". Memory performance was assessed by the memorization
      of 10 black and white pictures from the Brief Cognitive Screening Battery (BCSB).
      Results: No differences were found between men and women, nor for age group and
      educational level, in memory performance prediction before carrying out the
      memory task. There was a modest association (rho=0.11, p=0.041) between memory
      prediction and performance in immediate memory. On multivariate linear regression
      analyses, memory performance prediction was moderately significantly associated
      with immediate memory (p=0.061). Conclusion: In this study, sociodemographic
      variables did not influence memory prediction, which was only modestly associated
      with immediate memory on the Brief Cognitive Screening Battery (BCSB).

PMID- 29213943
TI  - Patients with dementia syndrome in public and private services in southern
      Brazil.
AB  - : Dementia is characterized by deficits in more than one cognitive domain,
      affecting language, praxis, gnosis, memory or executive functions. Despite the
      essential economic growth observed in many developing countries, especially over
      the last century, huge differences remain in health care, whether among nations
      themselves or across different regions of the same country. Objective: The aim of
      this study was to assess the management and main features of dementia, comparing
      public (PUBL) and private (PRIV) reference services. Methods: We performed a
      retrospective analysis of medical records of subjects with dementia.
      Sociocultural data, mean follow-up time in the service, Mini-mental State
      Examination (MMSE) scores at admission, main diagnosis of dementia, family
      history of dementia, comorbidities, imaging methods and treatment were assessed.
      Results: the time elapsed before admission in the service of the PUBL group
      (2.08+/-2.06 years) was higher than for the PRIV group (1.24+/-2.55 years)
      (p=0.0356); the MMSE score at admission in the PUBL group (15.05+/-8.16 years)
      was lower than in the PRIV group (18.95+/-6.69 years) (p=0.016); the PUBL group
      showed lower treatment coverage with cholinesterase inhibitors (52.94%) than the
      PRIV group (84.93%) (p=0.0001). Conclusion: Patients seeking the public health
      service have less access to medical care, reaching the system at more advanced
      stages of disease. The public service also offered lower pharmacological
      coverage.

PMID- 29213944
TI  - Assessment for apraxia in mild cognitive impairment and Alzheimer's dise.
AB  - Objective: To evaluate apraxia in healthy elderly and in patients diagnosed with
      Alzheimer's disease (AD) and Mild cognitive impairment (MCI). Methods: We
      evaluated 136 subjects with an average age of 75.74 years (minimum 60 years old,
      maximum 92 years old) and average schooling of 9 years (minimum of 7 and a
      maximum of 12 years), using the Mini-Mental State examination (MMSE), Cambridge
      Cognitive Examination (CAMCOG) and the Clock Drawing Test. For the analysis of
      the presence of apraxia, eight subitems from the CAMCOG were selected: the
      drawings of the pentagon, spiral, house, clock; and the tasks of putting a piece
      of paper in an envelope; the correct one hand waiving "Goodbye" movements; paper
      cutting using scissors; and brushing teeth. Results: Elder controls had an
      average score of 11.51, compared to MCI (11.13), and AD patients, whose average
      apraxia test scores were the lowest (10.23). Apraxia scores proved able to
      differentiate the three groups studied (p=0.001). In addition, a negative
      correlation was observed between apraxia and MMSE scores. Conclusion: We conclude
      that testing for the presence of apraxia is important in the evaluation of
      patients with cognitive impairments and may help to differentiate elderly
      controls, MCI and AD.

PMID- 29213945
TI  - Depression in elderly women resident in a long-stay nursing home.
AB  - : Depression is the most common psychiatric disorder among the elderly: it is
      present in 23-40% of community-dwelling elderly and in 25-80% of
      institutionalized elderly. Depressive symptoms are most prevalent in elderly
      women because they more readily seek healthcare services, are more vulnerable to
      stress and live longer than men. Objective: To investigate the prevalence of
      depression and its comorbidities in a long-stay nursing home (NH). Methods: This
      retrospective, descriptive, epidemiological study was performed at a NH in
      southern Brazil and comprised the first part of a larger project to determine
      depression and its relationship with psychosocial factors in NH residents.
      Sociodemographic and medical data were obtained through the examination of
      medical files from November 2012 to January 2013. Depression was defined as the
      diagnosis reported by physicians in medical files and scores on the Geriatric
      Depression Scale (15-item version) above 5. Other clinical and psychiatric
      diagnoses were obtained from medical files. Results: Out of a total of 142
      elderly women, 51.4% had at least one psychiatric disorder, the most common being
      depression, affective bipolar disorder and mental retardation. Almost one third
      (32.3%) of the elderly women were depressed. The ward containing the highest
      number of cognitively and physically independent women contained 41.3% of the
      total depressed elderly. A total of 52.1% of all depressed elderly had other
      associated clinical or psychiatric disorders, with mental retardation and
      hypothyroidism being the most frequent. Conclusion: The prevalence of dementia
      was high in this NH. Further studies evaluating the psychosocial factors involved
      in depressed elders should be conducted in an effort to prevent depression and
      promote mental health in institutionalized elders.

PMID- 29213946
TI  - Alois Alzheimer and vascular brain disease: Arteriosclerotic atrophy of the
      brain.
AB  - Alois Alzheimer is best known for his description of neurofibrillary changes in
      brain neurons of a demented patient, identifying a novel disease, soon named
      after him by Kraepelin. However, the range of his studies was broad, including
      vascular brain diseases, published between 1894 and 1902. Alzheimer described the
      clinical picture of Arteriosclerotic atrophy of the brain, differentiating it
      from other similar disorders. He stated that autopsy allowed pathological
      distinction between arteriosclerosis and syphilis, thereby achieving some of his
      objectives of segregating disorders and separating them from syphilis. His
      studies contributed greatly to establishing the key information on vascular brain
      diseases, predating the present state of knowledge on the issue, while providing
      early descriptions of what would be later regarded as the dimensional
      presentation of the now called "Vascular cognitive impairment", constituted by a
      spectrum that includes a stage of "Vascular cognitive impairment not dementia"
      and another of "Vascular dementia".

PMID- 29213948
TI  - In the June 2015 issue.

PMID- 29213947
TI  - Reversible dementia due to neurocysticercosis: Improvement of the racemose type
      with antihistamines.
AB  - Infection of the human central nervous system (CNS) by the larvae of Taenia
      solium, termed neurocysticercosis (NCC), is endemic in most developing countries,
      where it is a major cause of acquired seizures and other neurological morbidity,
      including neuropsychiatric symptoms. However, despite its frequent manifestation,
      some findings, such as cognitive impairment and dementia, remain poorly
      understood. Less commonly, NCC may affect the ventricular system and subarachnoid
      spaces and this form is known as extraparenchymal neurocysticercosis. A
      particular presentation of the subarachnoid form is called racemose
      cysticercosis, which has a progressive pattern, frequently leads to hydrocephalus
      and can be life-threatening. Here we review a case of the racemose variety of
      cysticercosis, complicated by hydrocephalus and reversible dementia, with
      remission of symptoms after derivation and that remained stable with use of
      dexchlorpheniramine. We discuss the challenges in diagnosis, imaging findings,
      treatment and follow-up of this disease.

PMID- 29213949
TI  - Teaching medical students about dementia: A brief review.
AB  - Underdeveloped nations have the largest absolute number of the world's elderly
      population. Approximately 10.7% of the Brazilian population comprises aged
      individuals. Aging populations are associated with a higher incidence of chronic
      degenerative diseases such as dementia. Demented individuals place a high burden
      of care on healthcare systems and family members. General practitioners should be
      able to diagnose the most common elderly diseases such as dementia since they act
      as gatekeepers to specialized care. In Brazil, many medical students work as
      general practitioners upon graduating. The present study shows some scenarios of
      medical schools worldwide, including Brazilian, regarding teaching on dementia.

PMID- 29213950
TI  - Mechanisms linking brain insulin resistance to Alzheimer's disease.
AB  - Several studies have indicated that Diabetes Mellitus (DM) can increase the risk
      of developing Alzheimer's disease (AD). This review briefly describes current
      concepts in mechanisms linking DM and insulin resistance/deficiency to AD.
      Insulin/insulin-like growth factor (IGF) resistance can contribute to
      neurodegeneration by several mechanisms which involve: energy and metabolism
      deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic
      reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS
      with increased production of neuro-inflammation and activation of pro-apoptosis
      cascade. Impairment in insulin receptor function and increased expression and
      activation of insulin-degrading enzyme (IDE) have also been described. These
      processes compromise neuronal and glial function, with a reduction in
      neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of
      AbetaPP-Abeta oligomeric fibrils or insoluble larger aggregated fibrils in the
      form of plaques that are neurotoxic. Additionally, there is production and
      accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate
      cytoskeletal collapse and synaptic disconnection.

PMID- 29213951
TI  - Factors associated with morphometric brain changes in cognitively normal aging.
AB  - Objective: Cognitive impairment is associated with reductions in brain weight and
      volume. The factors related to morphometric brain changes in cognitively normal
      aging remain unknown. We aimed to identify which clinical factors are associated
      with morphometric brain changes in cognitively normal aging. Methods: A cross
      sectional study of 414 subjects, >=50 years old submitted to clinical assessment
      and brain autopsy, after informed consent, was carried out at the Sao Paulo
      Autopsy Service, Brazil. Data on cognitive and functional evaluations were
      collected through structured interview applied to the next-of-kin. Brain weight
      (g) and volume (mL) measurements were obtained and adjusted for head
      circumference (cm). Associations between brain weight/volume and related factors
      were obtained through univariate and multivariate analysis. Results: Participants
      were predominantly male (60.4%), Caucasian (69%), with mean age of 67.1 +/- 10.9
      years. Mean brain weight was 1219.2 +/- 140.9 g, and mean brain volume was 1217.1
      +/- 152.3 mL. Head circumference was independently associated with low brain
      weight (p<0.001) and volume (p<0.001). Total and adjusted brain weight and volume
      decreased in some conditions. Female gender (p<0.001), hypertension (p<0.009),
      coronary artery disease (p<0.013) and walking assistance (p<0.011) were
      associated with lower adjusted brain weight while schooling was associated with
      higher adjusted brain weight (p<0.003). Female gender (p<0.001), age (p<0.001)
      and hypertension (p<0.011) were associated with low adjusted brain volume.
      Conclusion: Morphometric brain changes occur despite the absence of cognitive
      impairment and were predominantly associated with age, female gender, mobility
      impairment and cardiovascular conditions. Schooling may be a protective factor.

PMID- 29213952
TI  - Relationship between cognition and frailty in elderly: A systematic review.
AB  - Objective: The aim of this study was to analyze the relationship between
      cognition and frailty in the elderly. Methods: A systematic review on the
      currently existing literature concerning the subject was carried out. The search
      strategy included LILACS, SCOPUS, SciELO, PsycINFO, PubMed and Web of Science
      databases. Results: A total of 19 studies were selected for review, from which 10
      (52.6%) were cross-sectional and 9 (47.4%) longitudinal, and the majority
      Brazilian. All of the studies established a link between cognition and frailty.
      There was a relationship between components of frailty and the cognitive domains.
      Risk of Mild Cognitive Impairment (MCI), dementia and mortality were all
      evidenced in the relationship between frailty and cognitive impairment.
      Conclusion: The theory remains limited, but results show the variables that
      appear to be linked to cognition and frailty in elderly. This data can help in
      implementing actions to improve the quality of life among elderly.

PMID- 29213953
TI  - Brazilian preliminary norms and investigation of age and education effects on the
      Modified Wisconsin Card Sorting Test, Stroop Color and Word test and Digit Span
      test in adults.
AB  - : Executive functions are involved in a series of human neurological and
      psychiatric disorders. For this reason, appropriate assessment tools with age and
      education adjusted norms for symptom diagnosis are necessary. Objective: To
      present normative data for adults (19-75 year-olds; with five years of education
      or more) on the Modified Wisconsin Card Sorting Test (MWCST), Stroop color and
      word test and Digit Span test. Age and education effects were investigated.
      Methods: Three samples were formed after inclusion criteria and data analysis:
      MWCST (n=124); Digit Span (n=123), and Stroop test (n=158). Groups were divided
      into young (19-39), middle-aged (40-59) and older (60-75) participants with five
      to eight years of education and nine years of education or more. Two-way ANOVA
      and ANCOVA analyses were used. Results: Education effects were found in most
      variables of the three tasks. An age effect was only found on color naming and
      color-word naming speed from the Stroop test. No interactions were detected.
      Conclusion: In countries with heterogeneous educational backgrounds, the use of
      stratified norms by education to assess at least some components of executive
      functions is essential for an ethical and accurate cognitive diagnosis.

PMID- 29213954
TI  - Specific algorithm method of scoring the Clock Drawing Test applied in
      cognitively normal elderly.
AB  - : The Clock Drawing Test (CDT) is an inexpensive, fast and easily administered
      measure of cognitive function, especially in the elderly. This instrument is a
      popular clinical tool widely used in screening for cognitive disorders and
      dementia. The CDT can be applied in different ways and scoring procedures also
      vary. Objective: The aims of this study were to analyze the performance of
      elderly on the CDT and evaluate inter-rater reliability of the CDT scored by
      using a specific algorithm method adapted from Sunderland et al. (1989). Methods:
      We analyzed the CDT of 100 cognitively normal elderly aged 60 years or older. The
      CDT ("free-drawn") and Mini-Mental State Examination (MMSE) were administered to
      all participants. Six independent examiners scored the CDT of 30 participants to
      evaluate inter-rater reliability. Results and Conclusion: A score of 5 on the
      proposed algorithm ("Numbers in reverse order or concentrated"), equivalent to 5
      points on the original Sunderland scale, was the most frequent (53.5%). The CDT
      specific algorithm method used had high inter-rater reliability (p<0.01), and
      mean score ranged from 5.06 to 5.96. The high frequency of an overall score of 5
      points may suggest the need to create more nuanced evaluation criteria, which are
      sensitive to differences in levels of impairment in visuoconstructive and
      executive abilities during aging.

PMID- 29213955
TI  - Development of alternative versions of the Logical Memory subtest of the WMS-R
      for use in Brazil.
AB  - : The logical memory test of the Wechsler Memory Scale is one of the most
      frequently used standardized tests for assessing verbal memory and consists of
      two separate short stories each containing 25 idea units. Problems with practice
      effects arise with re-testing a patient, as these stories may be remembered from
      previous assessments. Therefore, alternative versions of the test stimuli should
      be developed to minimize learning effects when repeated testing is required for
      longitudinal evaluations of patients. Objective: To present three alternative
      stories for each of the original stories frequently used in Brazil (Ana Soares
      and Roberto Mota) and to show their similarity in terms of content, structure and
      linguistic characteristics. Methods: The alternative stories were developed
      according to the following criteria: overall structure or thematic content
      (presentation of the character, conflict, aggravation or complements and
      resolution); specific structure (sex of the character, location and occupation,
      details of what happened); formal structure (number of words, characters, verbs
      and nouns); and readability. Results: The alternative stories and scoring
      criteria are presented in comparison to the original WMS stories (Brazilian
      version). Conclusion: The alternative stories presented here correspond well
      thematically and structurally to the Brazilian versions of the original stories.

PMID- 29213956
TI  - The most frequently used tests for assessing executive functions in aging.
AB  - : There are numerous neuropsychological tests for assessing executive functions
      in aging, which vary according to the different domains assessed. Objective: To
      present a systematic review of the most frequently used instruments for assessing
      executive functions in older adults with different educational levels in clinical
      and experimental research. Methods: We searched for articles published in the
      last five years, using the PubMed database with the following terms:
      "neuropsychological tests", "executive functions", and "mild cognitive
      impairment". There was no language restriction. Results: 25 articles fulfilled
      all the inclusion criteria. The seven neuropsychological tests most frequently
      used to evaluate executive functions in aging were:[1] Trail Making Test (TMT)
      Form B;[2] Verbal Fluency Test (VFT) - F, A and S;[3] VFT Animals category;[4]
      Clock Drawing Test (CDT);[5] Digits Forward and Backward subtests (WAIS-R or WAIS
      III);[6] Stroop Test; and[7] Wisconsin Card Sorting Test (WCST) and its variants.
      The domains of executive functions most frequently assessed were: mental
      flexibility, verbal fluency, planning, working memory, and inhibitory control.
      Conclusion: The study identified the tests and domains of executive functions
      most frequently used in the last five years by research groups worldwide to
      evaluate older adults. These results can direct future research and help build
      evaluation protocols for assessing executive functions, taking into account the
      different educational levels and socio-demographic profiles of older adults in
      Brazil.

PMID- 29213957
TI  - Brazilian adaptation of the Hotel Task: A tool for the ecological assessment of
      executive functions.
AB  - : Over recent years, neuropsychological research has been increasingly concerned
      with the need to develop more ecologically valid instruments for the assessment
      of executive functions. The Hotel Task is one of the most widely used ecological
      measures of executive functioning, and provides an assessment of planning,
      organization, self-monitoring and cognitive flexibility. Objective: The goal of
      this study was to adapt the Hotel Task for use in the Brazilian population.
      Methods: The sample comprised 27 participants (three translators, six expert
      judges, seven healthy adults, ten patients with traumatic brain injuries and one
      hotel manager). The adaptation process consisted of five steps, which were
      repeated until a satisfactory version of the task was produced. The steps were as
      follows:(1) Translation;(2) Development of new stimuli and brainstorming among
      the authors;(3) Analysis by expert judges;(4) Pilot studies;(5) Assessment by an
      expert in business administration and hotel management. Results: The adapted
      version proved adequate and valid for the assessment of executive functions.
      However, further research must be conducted to obtain evidence of the
      reliability, as well as the construct and criterion validity, sensitivity and
      specificity, of the Hotel Task. Conclusion: Many neurological and/or psychiatric
      populations may benefit from the adapted task, since it may make significant
      contributions to the assessment of dysexecutive syndromes and their impact on
      patient functioning.

PMID- 29213958
TI  - Cognitive performance after ischaemic stroke.
AB  - : Cognitive impairment after stroke affects the patient recovery process.
      Therefore, the identification of factors associated with cognitive outcomes is
      important since it allows risk profiles of stroke survivors to be determined.
      Objective: To assess cognitive outcome of stroke outpatients and investigate
      associations among clinical and demographic variables, vascular risk factors,
      depression symptoms and functional ability; and to describe the
      neuropsychological profile of these patients. Methods: A cross-sectional design
      study was conducted. Subjects who suffered a first-ever ischaemic stroke 6 to 10
      months prior to data collection underwent neuropsychological assessment and
      screening for depressive symptoms and functional ability. The outcome "cognitive
      performance" was analyzed considering two groups: "cognitive impairment" and "no
      cognitive impairment". Results: There was a statistically significant association
      between cognitive impairment and female gender, age, stroke severity and
      functional ability. Regarding neuropsychological profile, the cognitive
      impairment group exhibited more generalized deficits in attention, visuospatial
      organization, verbal functions and verbal memory domains compared to the
      community control group. Conclusion: The occurrence of cognitive impairment among
      patients was high, especially in women, older participants, individuals with more
      severe stroke, and greater impairment in functional ability. Multiple cognitive
      domains are affected and this may hamper recovery and negatively impact
      independence and quality of life after stroke.

PMID- 29213959
TI  - Accuracy and reliability of the Pfeffer Questionnaire for the Brazilian elderly
      population.
AB  - : The aging population calls for instruments to assess functional and cognitive
      impairment in the elderly, aiming to prevent conditions that affect functional
      abilities. Objective: To verify the accuracy and reliability of the Pfeffer (FAQ)
      scale for the Brazilian elderly population and to evaluate the reliability and
      reproducibility of the translated version of the Pfeffer Questionnaire. Methods:
      The Brazilian version of the FAQ was applied to 110 elderly divided into two
      groups. Both groups were assessed by two blinded investigators at baseline and
      again after 15 days. In order to verify the accuracy and reliability of the
      instrument, sensitivity and specificity measurements for the presence or absence
      of functional and cognitive decline were calculated for various cut-off points
      and the ROC curve. Intra and inter-examiner reliability were assessed using the
      Interclass Correlation Coefficient (ICC) and Bland-Altman plots. Results: For the
      occurrence of cognitive decline, the ROC curve yielded an area under the curve of
      0.909 (95%CI of 0.845 to 0.972), sensitivity of 75.68% (95%CI of 93.52% to 100%)
      and specificity of 97.26%. For the occurrence of functional decline, the ROC
      curve yielded an area under the curve of 0.851 (95%CI of 64.52% to 87.33%) and
      specificity of 80.36% (95%CI of 69.95% to 90.76%). The ICC was excellent, with
      all values exceeding 0.75. On the Bland-Altman plot, intra-examiner agreement was
      good, with p>0.05consistently close to 0. A systematic difference was found for
      inter-examiner agreement. Conclusion: The Pfeffer Questionnaire is applicable in
      the Brazilian elderly population and showed reliability and reproducibility
      compared to the original test.

PMID- 29213960
TI  - Alzheimer and vascular brain disease: Senile dementia.
AB  - Alois Alzheimer is best known for his description of a novel disease,
      subsequently named after him. However, his wide range of interests also included
      vascular brain diseases. He described Senile dementia, a highly heterogeneous
      condition, and was able not only to distinguish it from syphilitic brain disease,
      but also to discriminate two clinicopathological subtypes, that may be labeled a
      "arteriosclerotic subtype", comparable to the present clinicopathological
      continuum of "Vascular cognitive impairment", and another as a "neurodegenerative
      subtype", characterized by primary [cortical] ganglion cell [nerve cells]
      degeneration, possibly foreshadowing a peculiar presenile disease that he was to
      describe some years later and would carry his name. He also considered the
      possibility of a senile presentation of this disease subtype, which was described
      by Oskar Fischer a short time later. Considering the clinicopathological
      overlapping features of the "arteriosclerotic subtype" of Senile dementia with
      Arteriosclerotic atrophy of the brain, it might be possible to consider that both
      represent a single condition.

PMID- 29213961
TI  - Autoimmune limbic encephalitis: A manifestation of systemic lupus erythematosus
      in the central nervous system.
AB  - Autoimmune limbic encephalitis (ALE) associated with systemic lupus erythematosus
      (SLE) is a rare entity with few reports in the literature to date. In general,
      ALE associated with SLE has a satisfactory response to immunosuppressive
      treatment (RIT), but the pathogenesis of this association is poorly understood
      and may include an autoimmunity component. We report a case study describing the
      diagnosis and management of limbic encephalitis in a patient with active Systemic
      Lupus Erythematosus disease (SLE) and past medical history of cancer (endometrial
      adenocarcinoma in 2004 and papillary urothelial carcinoma in 2011 with curative
      treatment), followed over a one-year period. We discuss the possible association
      between limbic encephalitis and all past neoplastic and immune-mediated
      conditions of this patient. In this particularly case, autoimmunity was the most
      relevant factor associated with limbic encephalitis given negative neoplastic
      screening. Moreover, a good response was observed to immunotherapy, not seen with
      paraneoplastic limbic encephalitis, which is associated with poor response. In
      this case, the association of ALE with SLE is possible, since laboratory testing
      disclosed lupic activity and the patient had involvement of other systems (such
      as hematologic) during the period. However, the presence of other surface
      membrane antibodies are possible in the search for alternative etiologies.

PMID- 29213962
TI  - Action of anti-TNF-alpha drugs on the progression of Alzheimer's disease: A case
      report.
AB  - The aim of this study was to describe a clinical case of a patient with
      Alzheimer's disease (AD) in use of an anti-TNF-alpha agent for rheumatoid
      arthritis (RA). The patient reported is an 81-year-old Caucasian man and retired
      teacher, diagnosed with RA in 2008 and AD in 2011. Treatment with donepezil was
      started in 2011 and the use of etanercept introduced in 2012. He was previously
      treated with adalimumab in 2010 for 18 months. In 2013, the subject was engaged
      in a clinical trial to assess a complementary non-pharmacological approach for
      AD, presenting significant cognitive improvement during the follow-up period. We
      propose the hypothesis of a synergistic effect of anti-TNF-alpha medication used
      for the treatment of RA as the cause of the improvement in cognitive response
      observed. These findings could suggest a possible use of this drug class in the
      therapeutic management of AD.

PMID- 29213963
TI  - In the September 2015 issue.

PMID- 29213964
TI  - Culture as a variable in neuroscience and clinical neuropsychology: A
      comprehensive review.
AB  - Culture is a dynamic system of bidirectional influences among individuals and
      their environment, including psychological and biological processes, which
      facilitate adaptation and social interaction. One of the main challenges in
      clinical neuropsychology involves cognitive, behavioral and functional assessment
      of people with different sociocultural backgrounds. In this review essay,
      examining culture from a historical perspective to ethical issues in cross
      cultural research, including the latest significant and publications, the authors
      sought to explore the main features related to cultural variables in
      neuropsychological practice and to debate the challenges found regarding the
      operational methods currently in use. Literature findings suggest a more
      comprehensive approach in cognitive and behavioral neuroscience, including an
      interface between elementary disciplines and applied neuropsychology. Thus, as a
      basis for discussion on this issue, the authors analyzed key-topics related to
      the study of new trends in sociocultural neuroscience and the application of
      their concepts from a clinical perspective.

PMID- 29213966
TI  - Neuropsychiatric symptoms in Vascular Cognitive Impairment: a systematic review.
AB  - : Neuropsychiatric symptoms or Behavioral and Psychological Symptoms of Dementia
      (BPSD) are common and invariably appear at some point during the course of the
      disease, mediated both by cerebrovascular disease and neurodegenerative
      processes. Few studies have compared the profiles of BPSD in Vascular Cognitive
      Impairment (VCI) of different subtypes (subcortical or cortical) and clinical
      stages (Vascular Cognitive Impairment No Dementia [VaCIND] and Vascular Dementia
      [VaD]). Objective: To review the BPSD associated with different subtypes and
      stages of VCI using the Neuropsychiatric Inventory (NPI). Methods: Medline,
      Scielo and Lilacs databases were searched for the period January 2000 to December
      2014, with the key words: "BPSD AND Vascular Dementia, "NPI AND Vascular
      Dementia" and "NPI AND VCI. Qualitative analysis was performed on studies
      evaluating BPSD in VCI, using the Neuropsychiatric Inventory (NPI). Results: A
      total of 82 studies were retrieved of which 13 were eligible and thus included.
      Among the articles selected, 4 compared BPSD in Subcortical Vascular Dementia
      (SVaD) versus Cortical-Subcortical Vascular Dementia (CSVaD), 3 involved
      comparisons between SVaD and VaCIND, 1 study analyzed differences between CSVaD
      and VaCIND, while 5 studies assessed BPSD in CSVaD. Subcortical and Cortical
      Subcortical VaD were associated predominantly with Apathy and Depression. VaCIND
      may present fewer behavioral symptoms than VaD. Conclusion: The profile of BPSD
      differs for different stages of VCI. Determining the most prevalent BPSD in VCI
      subtypes might be helpful for improving early diagnosis and management of these
      symptoms.

PMID- 29213967
TI  - Cognitive Change Questionnaire as a method for cognitive impairment screening.
AB  - : The Cognitive Change Questionnaire (CCQ) was created as an effective measure of
      cognitive change that is easy to use and suitable for application in Brazil.
      Objective: To evaluate whether the CCQ can accurately distinguish normal subjects
      from individuals with Mild Cognitive Impairment (MCI) and/or early stage dementia
      and to develop a briefer questionnaire, based on the original 22-item CCQ
      (CCQ22), that contains fewer questions. Methods: A total of 123 individuals were
      evaluated: 42 healthy controls, 40 patients with MCI and 41 with mild dementia.
      The evaluation was performed using cognitive tests based on individual
      performance and on questionnaires administered to informants. The CCQ22 was
      created based on a selection of questions that experts deemed useful in screening
      for early stage dementia. Results: The CCQ22 showed good accuracy for
      distinguishing between the groups. Statistical models selected the eight
      questions with the greatest power to discriminate between the groups. The AUC ROC
      corresponding to the final version of the 8-item CCQ (CCQ8), demonstrated good
      accuracy in differentiating between groups, good correlation with the final
      diagnosis (r=0.861) and adequate internal consistency (Cronbach's alpha=0.876).
      Conclusion: The CCQ8 can be used to accurately differentiate between normal
      subjects and individuals with cognitive impairment, constituting a brief and
      appropriate instrument for cognitive screening.

PMID- 29213965
TI  - The Genetics of Monogenic Frontotemporal Dementia.
AB  - Around 10-15% of patients diagnosed with frontotemporal dementia (FTD) have a
      positive family history for FTD with an autosomal dominant pattern of
      inheritance. Since the identification of mutations in MAPT (microtubule
      associated protein tau gene) in 1998, over 10 other genes have been associated
      with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations
      in GRN (progranulin) and C9orf72 (chromosome 9 open reading frame 72) are the
      most commonly identified in FTD cohorts. The association of FTD and motor neuron
      disease (MND) can be caused by mutations in C9orf72 and other genes, such as
      TARDBP (TAR DNA-binding protein), FUS (fused in sarcoma), UBQLN2 (ubiquilin 2).
      Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease
      of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP
      (valosing containing protein) and other recently identified genes.

PMID- 29213968
TI  - Brazilian transcultural adaptation of an instrument on physicians' knowledge and
      attitudes towards dementia.
AB  - Objective: The aim of this study was to obtain a Brazilian transcultural
      adaptation of an instrument developed in the United Kingdom for assessing the
      knowledge and attitudes towards dementia by physicians. Methods: The "Knowledge
      Quiz" (KQ) contains 14 items on epidemiology, diagnosis and management of
      dementia, while the "Attitude Quiz" contains 10 sentences about physicians'
      thoughts on the management of demented patients. The Quizzes were translated,
      back-translated and the resultant version applied to five physicians. Results:
      The transcultural equivalence process was performed and four items of the KQ
      needed adapting to the Brazilian context. After changes suggested by a panel of
      specialists, the final version was applied to another five physicians and the
      transcultural equivalence considered adequate. Conclusion: The Brazilian version
      of the instrument was successfully transculturally adapted for future validation
      and application in Brazil.

PMID- 29213969
TI  - Total output and switching in category fluency successfully discriminates
      Alzheimer's disease from Mild Cognitive Impairment, but not from frontotemporal
      dementia.
AB  - : Verbal fluency tasks require generation of words beginning with a letter
      (phonemic fluency; PF) or from a category (category fluency; CF) within a limited
      time period. Generally, total output on CF has been used to discriminate Mild
      Cognitive Impairment (MCI) from Alzheimer's disease (AD), while poor PF has been
      used as a marker for behavioral-variant frontotemporal dementia (bvFTD). However,
      in the absence of this disparate performance, further characterization of the
      task becomes necessary. Objective: We examined whether fluency, as well as its
      components, clustering (successively generated words belonging to a category) and
      switching (shifting between categories) carried diagnostic utility in
      discriminating AD from MCI and bvFTD. Methods: PF (letter 'P') and CF ('animals')
      tasks were administered in English to patients with MCI (n=25), AD (n=37), and
      bvFTD (n=17). Clustering and switching scores were calculated using established
      criteria. Results: Our findings suggested that up to 85% of AD and MCI could be
      successfully discriminated based on total number of responses and switching in CF
      alone. PF-CF disparity was not noted in AD or bvFTD. Performance on clustering or
      switching also proved insufficient to discriminate AD from bvFTD. Conclusion:
      Switching was found to be useful when differentiating AD from MCI. In AD and
      bvFTD, the course of progression of the disease may lead to attenuation of total
      number of responses produced on both tasks to an extent where clustering and
      switching may not be useful measures to discriminate these dementias from each
      other.

PMID- 29213970
TI  - Use of a modified version of the switching verbal fluency test for the assessment
      of cognitive flexibility.
AB  - Objective: Verbal fluency tests are widely used for the assessment of executive
      functions. However, traditional versions of the test depend on several cognitive
      factors beyond these components. The aim of this study was to evaluate the
      associations of a modified version of the verbal fluency with specific measures
      of executive functions. Methods: Sixty adults were evaluated using traditional
      versions of verbal fluency (animals/fruits) and a modified condition where
      subjects must switch between animals and fruits. Processing speed, semantic
      abilities, psychiatric symptoms and executive functions were also assessed.
      Results: Partial correlations between the verbal fluency tests and measures of
      executive functions, controlled for demographic, cognitive and psychiatric
      symptoms, suggest that cognitive flexibility has 9% shared variance with the
      verbal fluency test - category animals, 2 % with category fruits, 8% with total
      words in switching condition, and 20% with total correct word-pairs produced in
      switching condition. The other aspects of executive functions during the task had
      shared variance of between 1% and 7% with the verbal fluency tasks. Conclusion:
      The results suggest that correct word-pairs produced in switching verbal fluency
      may be a more specific measure for evaluating cognitive flexibility compared to
      other versions of verbal fluency.

PMID- 29213971
TI  - Performance of a sample of patients with Mild Cognitive Impairment (MCI),
      Alzheimer's Disease (AD) and healthy elderly on a lexical decision test (LDT) as
      a measure of pre-morbid intelligence.
AB  - Objective: The objective of this study was to describe the performance of healthy
      elderly patients with aging-related pathologies (MCI) and patients with AD on a
      lexical decision test. Methods: The study included 38 healthy elderly subjects,
      61 MCI and 26 AD patients from the Neurology Department of the Hospital das
      Clinicas, Behavioral and Cognitive Neurology Group. The neuropsychological
      instruments included the episodic memory test (RAVLT), subtests from the WAIS-III
      (Matrix Reasoning and Vocabulary) to determine estimated IQ, the Boston naming
      test (BNT) and Lexical Decision Test (LDT). Results: All groups differed on the
      MMSE, as expected according to their pathologies, memory tests, naming and
      estimated IQ. For the vocabulary and the LDT - measures of crystalized
      intelligence no differences were found. Conclusion: The LDT demonstrated that
      lexical decision can be used as a measure of pre-morbid IQ among the individuals
      assessed in a Brazilian sample.

PMID- 29213972
TI  - Cognitive performance and engagement in physical, social and intellectual
      activities in older adults: The FIBRA study.
AB  - : Cognitive decline in aging can negatively impact quality of life in the
      elderly. However, studies have shown that elderly engaged in advanced activities
      of daily living (AADLs) can maintain or enhance global cognitive function or
      specific domains. Objective: To investigate the relationship between engagement
      in AADLs and domains of cognition in elderly from seven different locations in
      Brazil. Methods: A cross-sectional study involving 2,549 elderly without
      cognitive deficits suggestive of dementia was conducted. Data were collected on
      sociodemographic characteristics, health status, the Mini-Mental State Exam
      (MMSE) by subdomain (orientation, memory, attention/calculus, language and
      constructional praxis), and engagement in AADL grouped under physical, social and
      intellectual activities. Results: Multivariate linear regression analysis
      revealed an association, albeit modest, between intellectual AADLs and the
      domains orientation, attention/calculus, language and constructional praxis
      (R2=0.005, 0.008, 0.021, and 0.021 respectively). Social AADLs were correlated
      with memory (R2=0.002) and language (R2=0.004) domains. No association was found
      between physical AADLs and MMSE domains. Schooling and family income were the
      sociodemographic variables exhibiting the strongest relationship with cognitive
      domains. Conclusion: The study found associations between intellectual and social
      AADLs with higher cognitive performance, suggesting that active aging can provide
      opportunities to attenuate cognitive decline in aging.

PMID- 29213973
TI  - Analysis of prototypical narratives produced by aphasic individuals and
      cognitively healthy subjects.
AB  - : Aphasia can globally or selectively affect comprehension and production of
      verbal and written language. Discourse analysis can aid language assessment and
      diagnosis. Objective: [1] To explore narratives that produce a number of valid
      indicators for diagnosing aphasia in speakers of Brazilian Portuguese.[2] To
      analyze the macrostructural aspects of the discourse of normal individuals.[3] To
      analyze the macrostructural aspects of the discourse of aphasic individuals.
      Methods: The macrostructural aspects of three narratives produced by aphasic
      individuals and cognitively healthy subjects were analyzed. Results: A total of
      30 volunteers were examined comprising 10 aphasic individuals (AG) and 20 healthy
      controls (CG). The CG included 5 males. The CG had a mean age of 38.9 years
      (SD=15.61) and mean schooling of 13 years (SD=2.67) whereas the AG had a mean age
      of 51.7 years (SD=17.3) and mean schooling of 9.1 years (SD=3.69). Participants
      were asked to narrate three fairy tales as a basis for analyzing the
      macrostructure of discourse. Comparison of the three narratives revealed no
      statistically significant difference in number of propositions produced by the
      groups. A significant negative correlation was found between age and number of
      propositions produced. Also, statistically significant differences were observed
      in the number of propositions produced by the individuals in the CG and the AG
      for the three tales. Conclusion: It was concluded that the three tales are
      applicable for discourse assessment, containing a similar number of propositions
      and differentiating aphasic individuals and cognitively healthy subjects based on
      analysis of the macrostructure of discourse.

PMID- 29213974
TI  - Executive functions as a potential neurocognitive endophenotype in anxiety
      disorders: A systematic review considering DSM-IV and DSM-5 diagnostic criteria
      classification.
AB  - : Evidence in the literature indicates that neurocognitive impairments may
      represent endophenotypes in psychiatric disorders. Objective: This study aimed to
      conduct a systematic review on executive functions as a potential neurocognitive
      endophenotype in anxiety disorder diagnosis according to the DSM-IV and DSM-5
      classifications. Methods: A literature search of the LILACS, Cochrane Library,
      Index Psi Periodicos Tecnico-Cientificos, PubMed and PsycInfo databases was
      conducted, with no time limits. Of the 259 studies found, 14 were included in
      this review. Results: Only studies on obsessive-compulsive disorder (OCD) were
      found. The executive function components of decision-making, planning, response
      inhibition, behavioral reversal/alternation, reversal learning and set
      shifting/cognitive flexibility were considered to be a neurocognitive
      endophenotypes in OCD. Conclusion: Further studies on executive functions as a
      neurocognitive endophenotype in other anxiety disorders are needed since these
      may have different neurocognitive endophenotypes and require other prevention and
      treatment approaches.

PMID- 29213975
TI  - Evaluation of quality of life and psychological aspects of Parkinson's disease
      patients who participate in a support group.
AB  - : Parkinson's disease (PD) is a neurodegenerative disorder that can dramatically
      impair patient quality of life (QoL). Objective: To analyze the QoL, motor
      capacity, depression, anxiety and social phobia of individuals who attended a
      patient support group (PSG) compared to non-participants. Methods: A cross
      sectional study was performed. The sample consisted of 20 individuals with PD who
      attended a PSG and another 20 PD patients who did not attend a support group for
      PD patients, serving as the control group (nPSG). All patients answered
      questionnaires on motor capacity (UPDRS), QoL (Parkinson's Disease Questionnaire-
      PDQ-39), depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory)
      and social phobia (Liebowitz Social Anxiety Scale). To determine data
      distribution, the Shapiro-Wilk test was performed. For comparison of means,
      Student's t-test was applied. In cases of asymmetry, the Mann-Whitney test was
      employed. To assess the association between the scales, Pearson's correlation
      coefficient (symmetric distribution) and Spearman's coefficient (asymmetric
      distribution) were applied. For the association between qualitative variables,
      Pearson's Chi-squared test was performed. A significance level of 5% (p<=0.05)
      was adopted. Results: Individuals in the PSG had a significantly better QoL
      (p=0.002), and lower depression (p=0.026), anxiety (p<0.001) and social phobia
      (p=0.01) scores compared to the nPSG. Conclusion: The participation of PD
      patients in social activities such as support groups is associated with better
      QoL and fewer symptoms of depression, anxiety and social phobia.

PMID- 29213976
TI  - Assessment of verbal and visuospatial working memory in mild cognitive impairment
      and Alzheimer's dementia.
AB  - : In addition to episodic memory impairment, working memory may also be
      compromised in mild cognitive impairment (MCI) or Alzheimer's dementia (AD), but
      standard verbal and visuospatial span tasks do not always detect impairments.
      Objective: To examine whether more complex verbal and visuospatial working memory
      tasks result in more reliable impairment detection. Methods: The Digit Span
      (forward, backward and sequencing), Spatial Span (forward and backward) and
      Spatial Addition test from the Wechsler batteries were administered to MCI and AD
      patients and performance compared to healthy older adult controls. Results:
      Results showed that both the MCI and AD patients had impaired performance on the
      Spatial Addition test. Both groups also had impaired performance on all three
      Digit Span conditions, but no differences were found between forward and backward
      conditions in any of the groups. The sequencing condition differed from the
      backward condition only in the AD group. Spatial Span performance was impaired in
      AD group patients but not in MCI patients. Conclusion: Working memory deficits
      are evident in MCI and AD even on standard neuropsychological tests. However,
      available tests may not detect subtle impairments, especially in MCI. Novel
      paradigms tapping the episodic buffer component of working memory may be useful
      in the assessment of working memory deficits, but such instruments are not yet
      available for clinical assessment.

PMID- 29213977
TI  - Alzheimer and vascular brain diseases: Focal and diffuse subforms.
AB  - Alois Alzheimer is best known for his description of the pre-senile
      neurodegenerative disease named after him. However, his previous interest in
      vascular brain diseases, underlying cognitive and behavioral changes, was very
      strong. Besides describing the Arteriosclerotic atrophy of the brain and the
      arteriosclerotic subtype of Senile dementia which he viewed as main forms of
      vascular brain diseases, he also identified and described a series of conditions
      he considered subforms. These may be divided, as suggested by the authors of the
      present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and
      apoplectic. The subforms of the three groups present characteristic
      neuropathological features and clinical, cognitive and behavioral manifestations.
      These provide the basis, together with part of the main forms, for the
      contemporary condition known as Vascular Cognitive Impairment.

PMID- 29213979
TI  - Editorial: Neuroimaging in dementias.

PMID- 29213978
TI  - A patient with a long history of relapsing psychosis and mania presenting with
      anti-NMDA receptor encephalitis ten years after first episode.
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered
      autoimmune disorder, in which antibodies target NMDARs in the brain, leading to
      their removal from synapses. Early in the disease course, patients often present
      with marked psychosis and mood disturbances (i.e. mania, depression), explaining
      why most of these patients are first seen by psychiatrists. Hence, autoimmune
      encephalitis is receiving growing attention from psychiatry, mainly owing to
      concerns over misdiagnosing immunomediated and potentially curable disorders as
      primary psychiatric disorders, such as schizophrenia or major depressive
      disorder. Although anti-NMDAR encephalitis occurs in the context of new-onset
      psychiatric symptoms, there is a lack of information on differential diagnosis
      and treatment of this disorder after a long-term diagnostic history of functional
      psychiatric disorders. We report a case of a patient with a long history of
      bipolar affective disorder evolving with anti-NMDAR encephalitis, initially
      misdiagnosed as non-organic psychosis.

PMID- 29213980
TI  - A new section: neuroimaging through clinical cases.

PMID- 29213981
TI  - Multimodality Imaging Approach in Alzheimer disease. Part I: Structural MRI,
      Functional MRI, Diffusion Tensor Imaging and Magnetization Transfer Imaging.
AB  - The authors make a complete review of the potential clinical applications of
      traditional and novel magnetic resonance imaging (MRI) techniques in the
      evaluation of patients with Alzheimer's disease, including structural MRI,
      functional MRI, diffusion tension imaging and magnetization transfer imaging.

PMID- 29213982
TI  - Multimodality Imaging Approaches in Alzheimer's disease. Part II: 1H MR
      spectroscopy, FDG PET and Amyloid PET.
AB  - In this Part II review, as a complement to the Part I published in this
      supplement, the authors cover the imaging techniques that evaluates the
      Alzheimer's disease according to the different metabolic and molecular profiles.
      In this section MR spectroscopy, FDG-PET and amyloid PET are deeply discussed.

PMID- 29213983
TI  - PET and the multitracer concept in the study of neurodegenerative diseases.
AB  - The complexity of the pathological reactions of the brain to an aggression caused
      by an internal or external noxa represents a challenge for molecular imaging.
      Positron emission tomography (PET) can indicate in vivo, anatomopathological
      changes involved in the development of different clinical symptoms in patients
      with neurodegenerative disorders. PET and the multitracer concept can provide
      information from different systems in the brain tissue building an image of the
      whole disease. We present here the combination of 18F-flourodeoxyglucose (FDG)
      and N-[11C-methyl]-L-deuterodeprenyl (DED), FDG and N-[11C-methyl] 2-(4'
      methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB and L-[11C]-3'4
      Dihydrophenylalanine (DOPA) and finally PIB and [15O]H2O.

PMID- 29213984
TI  - Neuroimaging in normal pressure hydrocephalus.
AB  - Normal pressure hydrocephalus (NPH) is a syndrome characterized by the triad of
      gait disturbance, mental deterioration and urinary incontinence, associated with
      ventriculomegaly and normal cerebrospinal fluid (CSF) pressure. The clinical
      presentation (triad) may be atypical or incomplete, or mimicked by other
      diseases, hence the need for supplementary tests, particularly to predict
      postsurgical outcome, such as CSF tap-tests and computed tomography (CT) or
      magnetic resonance imaging (MRI). The CSF tap-test, especially the 3 to 5 days
      continuous external lumbar drainage of at least 150 ml/day, is the only procedure
      that simulates the effect of definitive shunt surgery, with high sensitivity (50
      100%) and high positive predictive value (80-100%). According to international
      guidelines, the following are CT or MRI signs decisive for NPH diagnosis and
      selection of shunt-responsive patients: ventricular enlargement disproportionate
      to cerebral atrophy (Evans index >0.3), and associated ballooning of frontal
      horns; periventricular hyperintensities; corpus callosum thinning and elevation,
      with callosal angle between 40o and 90o; widening of temporal horns not fully
      explained by hippocampal atrophy; and aqueductal or fourth ventricular flow void;
      enlarged Sylvian fissures and basal cistern, and narrowing of sulci and
      subarachnoid spaces over the high convexity and midline surface of the brain. On
      the other hand, other imaging methods such as radionuclide cisternography, SPECT,
      PET, and also DTI or resting-state functional MRI, although suitable for NPH
      diagnosis, do not yet provide improved accuracy for identifying shunt-responsive
      cases.

PMID- 29213985
TI  - Dementia resulting from traumatic brain injury.
AB  - Traumatic brain injury (TBI) represents a significant public health problem in
      modern societies. It is primarily a consequence of traffic-related accidents and
      falls. Other recently recognized causes include sports injuries and indirect
      forces such as shock waves from battlefield explosions. TBI is an important cause
      of death and lifelong disability and represents the most well-established
      environmental risk factor for dementia. With the growing recognition that even
      mild head injury can lead to neurocognitive deficits, imaging of brain injury has
      assumed greater importance. However, there is no single imaging modality capable
      of characterizing TBI. Current advances, particularly in MR imaging, enable
      visualization and quantification of structural and functional brain changes not
      hitherto possible. In this review, we summarize data linking TBI with dementia,
      emphasizing the imaging techniques currently available in clinical practice along
      with some advances in medical knowledge.

PMID- 29213986
TI  - Dementia in motor neuron disease: Reviewing the role of MRI in diagnosis.
AB  - The superimposed clinical features of motor neuron disease (MND) and
      frontotemporal dementia (FTD) comprise a distinct, yet not fully understood,
      neurological overlap syndrome whose clinicopathological basis has recently been
      reviewed. Here, we present a review of the clinical, pathological and genetic
      basis of MND-FTD and the role of MRI in its diagnosis. In doing so, we discuss
      current techniques that depict the involvement of the selective corticospinal
      tract (CST) and temporal lobe in MND-FTD.

PMID- 29213987
TI  - Neuroimaging of HIV-associated neurocognitive disorders.
AB  - A significant increase in the incidence of cognitive impairment in HIV/AIDS
      patients has been continuously observed. Consequently, three classification
      categories of cognitive impairment have been proposed: asymptomatic
      neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), that
      correspond to the mild and intermediate forms, and HIV-associated dementia (HAD)
      for the most severe cases. HIV-associated neurocognitive disorders (HAND) is a
      broad term that encompasses these three categories. Moreover, the application of
      neuroimaging methods has led to a major breakthrough in understanding of the
      neurological changes in HIV, providing greater reliability in the exclusion of
      associated diseases and allowing earlier diagnosis. Therefore, abnormalities
      and/or specific neuroimaging elements may soon be incorporated into the HAND
      classification criteria, which will be of great value in the management of these
      diseases, including in the optimization of high CNS penetration antiretroviral
      regimens.

PMID- 29213988
TI  - Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild
      cognitive impairment and Alzheimer's disease: Correlations and differences
      between the two methods.
AB  - : Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET
      in the posterior cingulate cortex (PCC) has been associated with a higher
      conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD).
      Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed
      Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the
      relationships between the two modalities are scarce. Objective: To evaluate
      differences and possible correlations between the findings of rBGM and NAA/mI in
      the PCC of individuals with AD, MCI and of cognitively normal volunteers.
      Methods: Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal
      older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the
      PCC. The two methods were compared and possible correlations between the
      modalities were investigated. Results: The AD group exhibited rBGM reduction in
      the PCC when compared to the CG but not in the MCI group. MRS revealed lower
      NAA/mI values in the AD group compared to the CG but not in the MCI group. A
      positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI
      reduction in the PCC differentiated AD patients from control subjects with an
      area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93.
      Conclusion: rBGM and Naa/mI in the PCC were positively correlated in patients
      with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD
      patients from controls.

PMID- 29213989
TI  - Neuroimaging criteria and cognitive performance in vascular mild cognitive
      impairment: A systematic review.
AB  - : The recognition of Cerebrovascular Disease (CVD) at earlier clinical stages may
      favor the control of vascular risk factors and prevention of dementia. However,
      operational criteria for symptomatic phases at non-dementia stages are often
      difficult, as the current criteria normally require the evidence of extensive
      subcortical disease. Objective: To identify the neuroimaging profile of Vascular
      Mild Cognitive Impairment (VaMCI), the impact of those aspects over cognition and
      the neuropsychological tests that distinguished VaMCI from other groups. Methods:
      Searches were performed in Scopus, ISI and PsycINFO, using the following key
      terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no
      dementia" OR "vascular cognitive impairment not demented" OR "subcortical mild
      cognitive impairment". Results: Of 249 papers, 20 studies were selected. Ten of
      those included only patients with severe White Matter Hyperintensities (WMH),
      whereas 10 others admitted subjects with moderate-to-severe WMH. Both groups
      showed poor performances in Executive Function (EF) tasks in comparison to normal
      controls and other diagnostic groups. Among EF tests, those assessing "complex"
      EF abilities consistently distinguished VaMCI from other groups, regardless of
      the severity of WMH. VaMCI subjects with severe or moderate-to-severe WMH showed
      cognitive deficits in comparison with other groups. "Complex" EF tests were the
      most useful in differentiating those patients from the other groups. Conclusion:
      The occurrence of VaMCI may be associated with the presence of CVD at moderate
      levels; the detection of vascular damage at earlier stages may allow the adoption
      of therapeutic actions with significant effect-sizes.

PMID- 29213990
TI  - Modulation of cerebral haemodynamic response to olfactory stimuli by emotional
      valence detected by functional magnetic resonance imaging.
AB  - : Olfactory perception, although restricted to just a few contexts in everyday
      life, is key in medicine. Several dementia conditions have been associated with
      early loss of olfactory discrimination. Despite the fact that several brain areas
      have been associated with olfaction in functional magnetic resonance imaging
      (fMRI), the mechanisms by which emotional valence is conveyed to the brain are
      not fully understood. Methods: In this study, we compared cerebral activations by
      olfactory stimuli using different emotional valence stimuli on event-related
      fMRI. We used three standard olfactory odorants with different valence (positive,
      neutral and negative). Forty-three healthy subjects (22 males) were scanned on a
      3.0T MR system. Olfactory stimulation was attained through a delivery system
      synchronized with image acquisition and subjects' breathing instructions. fMRI
      data analysis was performed by the FSL package (Oxford University) including head
      movement correction, GLM modeling of the neurovascular (BOLD) response and group
      activation maps produced at p<0.05and corrected for multiple comparison. Results:
      Increased cerebral responses within the anterior cingulate, amygdaloid nuclei, as
      well as the dorsolateral prefrontal, occipital and orbitofrontal cortices were
      observed in positive and negative valence conditions, while response to neutral
      valence arousal was less intense and not observed in the amygdaloid complex. The
      most significant statistical response aroused from the stimuli clusters was
      observed in the negative condition. Conclusion: The results of the present study
      support the hypothesis that neutral stimuli may be more sensitive to early losses
      in pathological conditions, particularly dementia.

PMID- 29213992
TI  - Contrast enhancement in the mammillary bodies: An easily missed sign of Korsakoff
      syndrome.

PMID- 29213991
TI  - C9ORF72 and the FTD-ALS spectrum: A systematic review of neuroimaging studies.
AB  - Objective: To perform a systematic review of the literature on the neuroimaging
      investigation of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis
      (ALS) associated with C9ORF72 mutation. Methods: The search was performed on
      PubMed and LILACS with the following terms: C9ORF72, MRI, SPECT, PET, ALS, FTD.
      No filters were added. Results: Twenty articles were selected. Most studies found
      consistent involvement of frontotemporal regions in C9ORF72 carriers, including
      prefrontal cortex, and also cingulate, subcortical regions, especially the
      thalami, and posterior regions such as the parietal and occipital lobes.
      Functional connectivity was also explored and impaired sensorimotor connectivity
      in striatum and thalami was found in behavioral variant FTD C9ORF72 carriers.
      Some papers have reported an absence of significant abnormalities on brain
      imaging. Conclusion: The inclusion of patients at different stages of the
      disease, differences in neuroimaging methods across studies, and distinct
      clinical phenotypes associated with C9ORF72 may account for the heterogeneity of
      results.

PMID- 29213993
TI  - Magnetic ressonance imaging in the diagnosis of Creutzfeldt-Jakob disease: Report
      of two cases.
AB  - Creutzfeldt-Jacob disease (CJD) is a rare condition caused by a pathogenic prion
      protein that evolves with rapidly progressive dementia and death. The clinical
      presentation may sometimes be misleading. Magnetic Resonance Imaging (MRI) aids
      diagnosis with patterns that can guide or confirm clinical hypotheses. Two cases
      of rapidly progressive dementia with ataxia, myoclonus and restricted diffusion
      on MRI in cortical/basal ganglia are presented to draw attention to CJD.

PMID- 29213994
TI  - Cadasil - genetic and ultrastructural diagnosis. Case report.
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) is a hereditary disorder which affects the cerebral
      vasculature due to mutations in the NOTCH 3 gene. The diagnosis may be
      established through genetic testing for detection of these mutations and/or by
      skin biopsy. We report a case of the disorder in a female patient, who presented
      recurrent transient ischemic attacks that evolved to progressive subcortical
      dementia. Neuroimaging disclosed extensive leukoaraiosis and lacunar infarcts.
      The genetic analysis for NOTCH 3 was confirmatory. The ultrastructural
      examination of the skin biopsy sample, initially negative, confirmed the presence
      of characteristic changes (presence of granular osmiophilic material inclusions
      [GOM]), after the analysis of new sections of the same specimen. The present
      findings indicate that negative findings on ultrastructural examinations of
      biopsy should not exclude the diagnosis of the disease and that further analyses
      of the sample may be necessary to detect the presence of GOM.

PMID- 29213995
TI  - LRSim: A Linked-Reads Simulator Generating Insights for Better Genome
      Partitioning.
AB  - Linked-read sequencing, using highly-multiplexed genome partitioning and
      barcoding, can span hundreds of kilobases to improve de novo assembly, haplotype
      phasing, and other applications. Based on our analysis of 14 datasets, we
      introduce LRSim that simulates linked-reads by emulating the library preparation
      and sequencing process with fine control over variants, linked-read
      characteristics, and the short-read profile. We conclude from the phasing and
      assembly of multiple datasets, recommendations on coverage, fragment length, and
      partitioning when sequencing genomes of different sizes and complexities. These
      optimizations improve results by orders of magnitude, and enable the development
      of novel methods. LRSim is available at https://github.com/aquaskyline/LRSIM.

PMID- 29213996
TI  - Gut microbiota, epigenetic modification and colorectal cancer.
AB  - Micro-organisms contain 90% of cells in human body and trillions foreign genes
      versus less than 30 thousand of their own. The human colon host various species
      of microorganisms, appraised at more than 1014 microbiota and contained of over a
      thousand species. Although each one's profile is separable, the relative
      abundance and distribution of bacterial species is the same between healthy ones,
      causing conservation of each person's overall health. Germline DNA mutations have
      been attributed to the less than 5% of CRC occurrence while more than 90% is
      associated with the epigenetic regulation. The most ubiquitous environmental
      factor in epigenetic modification is gut microbiota. Disruptive changes in the
      gut microbiome strongly contributed to the improvement of colorectal cancer. Gut
      microbiota may play critical role in progression of CRC via their metabolite or
      their structural component interacting with host intestinal epithelial cell
      (IEC). Herein we discuss the mechanism of epigenetic modification and its
      implication in CRC development, progression even metastasis by gut microbiota
      induction.

PMID- 29213997
TI  - Cloning, optimization of induction conditions and purification of Mycobacterium
      tuberculosis Rv1733c protein expressed in Escherichia coli.
AB  - Background and Objectives: Rv1733c is a latency antigen from Mycobacterium
      tuberculosis, a probable integral-membrane protein with promiscuous T-cell and B
      cell epitopes, making it a potential vaccine candidate against tuberculosis. This
      study aimed to clone and optimize the expression of recombinant Rv1733c in
      Escherichia coli for purification. Materials and Methods: Chemically synthesized
      rv1733c coding sequence was cloned in pET-23a(+) followed by transforming E. coli
      BL21 (DE3) cells. To evaluate the induction conditions for optimized expression,
      factorial design of experiments was employed using four different media as well
      as four levels of isopropyl-b-D-thiogalactopyranosid [IPTG] concentration and
      duration of induction. The recombinant protein was then purified using a His-tag
      purification kit and detected through western blotting. Results: Recombinant
      Rv1733c (> 24 kDa) was expressed and accumulated in the cytoplasm of the E. coli
      cells. Medium composition showed the most significant effect on the yield of the
      recombinant protein (P = 0.000). The highest yield of recombinant Rv1733c
      occurred in the presence of 0.4 mM of IPTG in Terrific Broth medium (containing
      1.2% tryptone, 2.4% yeast extract, 72 mM K 2 HPO 4 , 17 mM KH 2 PO 4 and 0.4%
      glycerol) after 10 h at 37 degrees C. Under these conditions, the expression
      level was around 0.5 g/L of culture medium. Purified Rv1733c was detected by an
      anti-polyhistidine antibody and a tuberculosis patient's serum. Systematic
      optimization of induction conditions gave us high yield of recombinant
      polyhistidine-tagged Rv1733c in E. coli which was successfuly purified.
      Conclusion: We believe that the purified Rv1733c recombinant protein from M.
      tuberculosis might be a good candidate for vaccine production against
      tuberculosis.

PMID- 29213998
TI  - Phenotypic and genetic characterization of beta-lactam resistance in Klebsiella
      from retail chicken meat in Mansoura, Egypt.
AB  - Background and Objectives: This study was undertaken to characterize
      antimicrobial resistance phenotypes and genes encoding extended spectrum beta
      lactamases (ESBLs) in Klebsiella isolated from retail chicken meat in Mansoura,
      Egypt. Materials and Methods: Three hundred sixty chicken meat samples from 120
      eviscerated chicken carcasses (3 cuts each) collected randomly from local retail
      chicken shops in Mansoura, Egypt during the period from April to June 2015, were
      assayed for the presence of Klebsiella by conventional bacteriological methods.
      Antimicrobial sensitivity for 12 antimicrobials using disk diffusion, ESBL
      phenotypic confirmation and PCR characterization of ESBL-encoding genes (blaTEM ,
      blaCTX-M , blaOXA , blaSHV and blaCMY ) were performed. Results: Klebsiella was
      identified from 22.2% (80/360) of the samples. Of the 12 antimicrobials tested,
      multidrug resistance (MDR; resistance to >=3 of the antimicrobial classes) was
      observed in 96.25% (77/80) of the Klebsiella isolates. All the isolates were
      resistant to cefotaxime, ceftriaxone and aztreonam. ESBL-producers were
      phenotypically confirmed in 48.75% (39/80) of the isolates. The highest values
      (0.75 and 0.67) of multiple antibiotic resistance (MAR) significantly occurred in
      ESBL-producing isolates. PCR findings showed a significantly higher occurrence of
      beta-lactamase encoding genes in ESBL (94.9%, 37/39) than non-ESBL producing
      isolates (4.9%, 2/41). The distribution of blaTEM , blaCTX-M and blaOXA among
      ESBL-producing isolates was 84.6%, 30.8% and 25.6%, respectively. Conclusion:
      Efficient monitoring and tracking of MDR, especially beta-lactam resistance, in
      food sources is essential to predict the potential hazards for human infections.

PMID- 29213999
TI  - Genetic and phenotypic study of methicillin-resistant Staphylococcus aureus among
      patients and health care workers in Mansoura University Hospital, Egypt.
AB  - Background and Objectives: Staphylococcus aureus is common pathogen that is
      associated with many hospital acquired infections. The virulence of S. aureus is
      identified with resistance to antibiotics especially to methicillin. Therefore
      the aims of the present study were to detect the carrier rates of methicillin
      resistant S. aureus (MRSA) among health care Workers (HCWs) and patients and to
      compare use of specific chromogenic agar for MRSA culture with PCR for detection
      of MRSA genes. Materials and Methods: Samples obtained were subjected to full
      microbiological laboratory studies involving culture on specific chromogenic
      medium and antibiotics susceptibility testing for detection of MRSA and their
      resistance rates to other commonly used antibiotics. Furthermore multiplex PCR
      was carried out to detect SCCmecA genes. Results: Staphylococcus aureus was
      isolated from 70 (29.9%) of the studied subjects. MRSA isolates (n=28) had high
      resistance rates for the used antibiotics and the most common resistance was for
      ciprofloxacin and chloramphenicol (57.1% for each). MRSA was isolated mainly from
      health care workers (17.02%). The frequency of SCCmecA was 60.7% for type I, 25%
      for type III and 14.3% for type II. Chromogenic agar identified correctly MRSA
      isolates in 92.9%. PCR was positive in all isolates with resistance to cefoxitin
      disc. Conclusions: The present study highlights that MRSA carriage is common
      among health care workers in one Egyptian tertiary care hospital. The major
      genotype of MRSA is belonging to SCCmecA type I followed by type III and type II.
      ChromID medium is an accurrate culture method for detection of MRSA compared to
      molecular method.

PMID- 29214000
TI  - Role of antigen-43 on biofilm formation and horizontal antibiotic resistance gene
      transfer in non-O157 Shiga toxin producing Escherichia coli strains.
AB  - Background and Objectives: The objectives of this study were to evaluate the
      antibiotic resistance profiles, biofilm formation, presence of antigen 43 (Ag43)
      gene, and transfer of antibiotic resistance phenotype among non-O157 Shiga toxin
      producing Escherichia coli (STEC). Materials and Methods: From October 2014 to
      November 2015 a total of 276 stool samples were collected from healthy calves,
      goats and 395 patients with the sign of nonbloody diarrhea and screened for
      presence of stx and serotype O157 genes by polymerase chain reaction (PCR)
      technique. Susceptibility to 14 antibiotics was determined as per CLSI guideline.
      Presence of Ag43 and intimin (eaeA) genes were detected by PCR. Biofilm formation
      was measured by microtiter plate method. Conjugation was carried out by membrane
      filter technique. Results: We isolated 74 (93.6%) non-O157 STEC strains from 41
      calves, 33 goats and 5 (6.3%) patients' stools, however, no O157 serotype was
      detected in our study. Resistance was observed most commonly to tobramycin
      (66.2%), kanamycin (48.6%), and amikacin (29.7%) and less frequently to
      ciprofloxacin (4.1%), amoxicillin-clavulanic acid (5.4%), and ceftriaxone (9.5%)
      in isolates recovered from calves and goats fecal samples, whereas, all human
      isolates were sensitive to ceftazidime, ciprofloxacin, tobramycin and imipenem,
      respectively. Furthermore, Ag43 was detected in 60 STEC isolated from animals and
      5 human origins (no eaeA gene was found in this study). Biofilm formation from
      Ag43+ and Ag43- colonies showed 20 isolates with strong biofilm activities.
      Cefotaxime resistance phenotype was transferred to E. coli ATCC 25922.1 (Nalr) by
      conjugation at a frequency of 1.6*10-4. Conclusion: From the above results we
      concluded that, human infections with non-O157 STEC were significantly low in
      Kerman. Ag43 was insignificant with biofilm quantity in most cases.

PMID- 29214001
TI  - Evaluating the relationship between serum immunoglobulin G (IgG) and A (IgA) anti
      CagA antibody and the cagA gene in patients with dyspepsia.
AB  - Background and Objectives: The cytotoxin-associated gene (cag) pathogenicity
      island is reported to be a major virulence factor of Helicobacter pylori
      infection. It is previously reported that the cagA-positive strains are more
      virulent, so it can be postulated that the cagA-positive gastritis will be more
      severe and the serum immunoglobulin G (IgG) and A(IgA) anti-CagA antibody titer
      will be higher. The aim of this study was to compare the relationship between IgG
      and IgA anti-CagA antibody and the cagA gene expression in patients with
      dyspepsia. Serum samples obtained from 130 dyspeptic patients with positive H.
      pylori in histological and Geimsa staining were tested for serum IgG and IgA anti
      CagA antibody using the enzyme-linked immunosorbent Assay. The expression of the
      cagA gene was determined using PCR on the biopsy samples, taken via endoscopy.
      Results: In our material, the sensitivity of IgG anti-CagA antibody in
      identifying patients with a proven infection with the cagA-positive strains was
      97.67%, and the negative likelihood ratios was 0.06. There was not significant
      correlation between serum IgA anti-CagA and the expression of the cagA gene among
      the dyspeptic patients. Conclusion: The IgG antibody titer was significantly
      higher in our patients with the cagA-positive H. pylori strain. However, in daily
      practice, the level of the IgG antibody titer cannot predict whether or not an
      individual carries a cagA-positive H. pylori strain, because there is a major
      overlap in the IgG antibody titer between the cagA-positive and cagA-negative
      patients.

PMID- 29214002
TI  - Antibacterial activity of poly-l-arginine under different conditions.
AB  - Background and Objectives: Arginine-rich peptides are an important class of
      antimicrobial peptides (AMPs) that exert their antibacterial activity via a lytic
      mechanism. Although the antibacterial activity of arginine-rich peptides has been
      already evaluated, no reports have so far been evaluated the influence of
      reaction conditions on their antimicrobial potential. The aim of the present
      study was to investigate the influence of pH, temperature, and glycine on
      antibacterial activity of poly-l-arginine (PLA) with a molecular weight of 5-15
      kDa against Escherichia coli O157:H7 and Staphylococcus aureus. Materials and
      Methods: The percentage of growth inhibition of PLA against both bacteria was
      analyzed at various pH, temperatures and sub-inhibitory concentrations of glycine
      by two-fold broth microdilution method. Results: The results showed that PLA had
      antibacterial activity against E. coli O157:H7 and S. aureus and the inhibitory
      effect increased with increasing PLA concentration. The antimicrobial activity of
      PLA against both microorganisms was higher in basic media than under acidic or
      neutral conditions. At 1/2 times the MIC, heat treatment intensified the toxicity
      of PLA against E. coli O157:H7 whereas the susceptibility to PLA seems to be
      temperature independent for S. aureus. The MICs of glycine against E. coli
      O157:H7 and S. aureus were 12.5 and 25 mg ml-1, respectively. The antibacterial
      activity of PLA against both microorganisms increased, as indicated by the
      increasing growth inhibition percentage of this peptide with increasing glycine
      concentration. Conclusion: The antibacterial activity of PLA against S. aureus
      and E. coli O157:H7 depends on pH and glycine concentration.

PMID- 29214003
TI  - No molecular evidence of Borna disease virus among schizophrenia and bipolar
      disorder patients in Iran.
AB  - Background and Objectives: Viruses have been suggested as one of the risk factors
      for psychiatric disorders. Among infectious agents Borna disease virus (BDV) has
      been known as a neurotropic virus which is able to cause neurological disorders
      in different animals. Recently there were controversial findings about BDV
      association with pathogenesis of human psychotic disorders. Materials and
      Methods: Here we performed a nested reverse transcription polymerase chain
      reaction for detection of BDV P40 RNA in peripheral blood mononuclear cell
      samples of schizophrenia (SC), bipolar disorder (BD) patients and healthy
      controls (HCs). Results: Only one out of 120 (0.8 %) psychiatric patients and two
      samples (2.7%) in 75 HCs showed positive results. There were no significant
      molecular evidence of BDV infection in 120 psychotic patients (60 SC and 60 BD)
      and 75 matched HCs. Conclusion: Our findings showed no association between BDV
      infection and pathogenesis of these psychiatric disorders. This is an interesting
      issue given both the as yet un-clarified role of BDV in human mental disorders
      and addressing patients in the so far under-investigating Middle East era.

PMID- 29214004
TI  - Prevalence of cryptococcal antigen positivity among HIV infected patient with CD4
      cell count less than 100 of Imam Khomeini Hospital, Tehran, Iran.
AB  - Background and Objectives: Cryptococcal meningitis is one of the main
      opportunistic infections associated with human immunodeficiency virus (HIV)
      infection. Despite the present and increasingly availability of specific
      treatment for cryptococcosis, the mortality rate of this infection is still high,
      particularly in patients with advanced immunsupression and advanced cryptococcal
      diseases. Materials and Methods: This Prospective Cohort study was conducted at
      Imam Khomeini hospital in Tehran, Iran. Serum cryptococcal antigen was detected
      using the Lateral Flow Assay (LFA) There were 86 HIV-infected patients included
      in this study. Results: There were 86 HIV-infected patients in this study. The
      prevalence of positive serum cryptococcal antigen was 0% (0 of 86). Conclusion:
      The prevalence of cryptococcal infection among patients with advanced acquired
      immunodeficiency syndrome (AIDS) in the Iran is very low (<3%) thus the screening
      test for cryptococcal antigenemia dose not save lives and is not cost-effective
      in Iranian population.

PMID- 29214005
TI  - Semantics-Powered Healthcare Engineering and Data Analytics.

PMID- 29214006
TI  - Biomechanics in Musculoskeletal Health.

PMID- 29214007
TI  - Cytokine levels and associations with symptom severity in male and female
      children with autism spectrum disorder.
AB  - Background: Autism spectrum disorders (ASDs) are complex, pervasive, and
      heterogeneous neurodevelopmental conditions with varying trajectories,
      significant male bias and largely unknown etiology. However, an understanding of
      the biological mechanisms driving pathophysiology is evolving. Immune system
      aberrations, as identified through cytokine profiles, are believed to have a role
      in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as
      well as provide biological markers of response to effective treatments. Research
      exploring the relationship between cytokine profiles and ASD symptoms is,
      however, in its infancy. The objective of this study was to explore relationships
      between cytokine levels and the severity of ASD and other clinical traits.
      Methods: Multiplex assay techniques were used to measure levels of 27 cytokines
      in plasma samples from a cohort of 144 children diagnosed with ASD. Results:
      Overall, results showed a significant negative association between platelet
      derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a
      significant interaction with sex suggested a different immune profile for females
      compared to males. ASD symptom severity was negatively associated with levels of
      4 cytokines, IL-1beta, IL-8, MIP-1beta, and VEGF, in females, but not in males.
      Conclusions: Results of the present study suggest that an altered cytokine
      response or profile is associated with the severity of ASD-related symptoms, with
      sex a potential modifier of this relationship. Further research in larger
      populations which recognizes the importance of sex comparisons and longitudinal
      assessments are now required to extend and further describe the role of the
      immune system in ASD.

PMID- 29214008
TI  - Comparing growth in surface and cave morphs of the species Astyanax mexicanus:
      insights from scales.
AB  - Background: Life in the darkness of caves is accompanied, throughout phyla, by
      striking phenotypic changes including the loss or severe reduction in eyes and
      pigmentation. On the other hand, cave animals have undergone constructive
      changes, thought to be adaptive, to survive in this extreme environment. The
      present study addresses the question of the evolution of growth in caves, taking
      advantage of the comparison between the river-dwelling and the cave-dwelling
      morphs of the Mexican tetra, Astyanax mexicanus. Results: A sclerochronology
      approach was undertaken to document the growth of the species in these two very
      distinct habitats. Scales from 158 wild Astyanax mexicanus specimens were
      analyzed from three caves (Pachon, Tinaja and Subterraneo) and two rivers (Rio
      Gallinas and Arroyo Lagarto) in San Luis Potosi and Tamaulipas, Mexico. A 10-13%
      reduction in scales size was observed in the cave morphs compared to the surface
      morphs. Age could be reliably inferred from annual growth increments on the
      scales from the two morphs of the species. Further comparisons with growth curves
      in laboratory conditions, obtained using the von Bertalanffy growth model, were
      also performed. In the wild and in the laboratory, cavefish originating from the
      Pachon cave reached smaller sizes than surface fish from three different
      locations: Rio Gallinas and Arroyo Lagarto (wild sampling) and Texas (laboratory
      population), respectively. Wild Pachon cavefish also seemed to grow to smaller
      sizes than the two other wild cavefish populations studied, Tinaja and
      Subterraneo. Finally, growth in the laboratory was faster than in the wild,
      particularly in the two first years of life. Conclusions: These data suggest that
      cavefish originating from the Pachon cave are subjected to an intrinsic
      limitation of their final size, which is at least in part independent from
      energy/food availability. This growth limitation may be an advantageous way of
      limiting energy expenditure and food needs in the cave environment. Moreover,
      growth regulation evolved differently in independently evolved cave populations.
      These results are discussed with regard to the sources of energy or general
      ecological conditions present in caves, and to the differences in behavior or
      feeding skills known in cavefish.

PMID- 29214009
TI  - The role of HoxA11 and HoxA13 in the evolution of novel fin morphologies in a
      representative batoid (Leucoraja erinacea).
AB  - Background: Batoids exhibit unique body plans with derived fin morphologies, such
      as the anteriorly expanded pectoral fins that fuse to the head, or distally
      extended anterior pelvic fin lobes used for a modified swimming technique
      utilized by skates (Rajidae). The little skate (Leucoraja erinacea), exhibits
      both of these unique fin morphologies. These fin modifications are not present in
      a typical shark body plan, and little is known regarding the mechanisms
      underlying their development. A recent study identified a novel apical ectodermal
      ridge (AER) associated with the development of the anterior pectoral fin in the
      little skate, but the role of the posterior HoxA genes was not featured during
      skate fin development. Results: We present the first evidence for HoxA expression
      (HoxA11 and HoxA13) in novel AER domains associated with the development of three
      novel fin morphologies in a representative batoid, L. erinacea. We found HoxA13
      expression associated with the recently described novel AER in the anterior
      pectoral fin, and HoxA11 expression in a novel AER domain in the anterior pelvic
      fin that we describe here. We find that both HoxA11 and HoxA13 are expressed in
      claspers, and while HoxA11 is expressed in pelvic fins and claspers, HoxA13 is
      expressed exclusively in developing claspers of males. Finally, HoxA11 expression
      is associated with the developing fin rays in paired fins. Conclusion: Overall,
      these results indicate that the posterior HoxA genes play an important role in
      the morphological evolution of paired fins in a representative batoid. These data
      suggest that the batoids utilize a unique Hox code, where the posterior HoxA
      genes exhibit distinct expression patterns that are likely associated with
      specification of novel fin morphologies.

PMID- 29214010
TI  - Giant cell tumour of the distal radius/ulna: response to pre-operative treatment
      with short-term denosumab.
AB  - Background: Treatment of giant cell tumour of bone (GCTB) of the distal
      radius/ulna poses a surgical challenge, as complex reconstructive surgery may be
      required. This study evaluates the clinical, radiological and pathological
      findings in five cases of GCTB of the distal forearm where a 3 month course of
      denosumab was given prior to surgery. Methods: Patients with biopsy proven distal
      forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery
      (curettage and cementation) were included. Wrist pain and function were assessed
      using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT
      were performed pre-treatment and 2 months after initiation of denosumab therapy.
      Histological comparison was made between the original biopsy and surgical
      curettage specimens. Results: Five patients with an average age of 25 years were
      included in the study. Improvement in wrist pain and function was seen in all
      patients with the average MMWS increasing from 30 pre-treatment to 85 at 3
      months. Plain radiographs demonstrated marginal sclerosis in all cases with
      reconstitution of cortical and subarticular bone by 2 months; internal matrix
      sclerosis and osseous consolidation was more variable. Increased tumour
      heterogeneity and low signal were observed on T2-weighted MR images. PET/CT
      revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months.
      Histology showed disappearance of osteoclasts and increased fibro-osseous tissue.
      Denosumab treatment has the potential to facilitate salvage surgery, thus
      avoiding bone resection and graft reconstruction. A good outcome was achieved
      apart from local recurrence in one case. Follow up ranged from 17 to 54 months.
      Conclusion: Distal forearm GCTB responds clinically, radiologically and
      histologically to a short course of pre-operative denosumab therapy, which has
      the potential to facilitate salvage surgery.

PMID- 29214011
TI  - Long non-coding RNA H19 regulates E2F1 expression by competitively sponging
      endogenous miR-29a-3p in clear cell renal cell carcinoma.
AB  - Background: Numerous recent studies indicate that the long non-coding RNAs
      (lncRNAs) are frequently abnormal expressed and take critical roles in many
      cancers. Renal cell carcinoma is the secondary malignant tumors in the urinary
      system and has high mortality and morbidity. Around 80% of RCCs is clear cell
      renal cell carcinoma (ccRCC) and is characterized by high metastasis and relapse
      rate. However, the clinical significances of lncRNAs in ccRCC are still unknown.
      Methods: The human cancer lncRNA PCR array (Yingbio) was performed to detect the
      differentially expressed lncRNAs in human ccRCC samples. Real-time PCR (RT-PCR),
      dual-luciferase assay, RNA binding protein immunoprecipitation (RIP) assay,
      transwell assay, CCK-8 assay, and western blot were performed to explore the
      molecular mechanism of lncRNAs in ccRCC cell migration and invasion. Results: In
      this study, lncRNA-H19 was high expressed and negatively correlated with miR-29a
      3p in ccRCC. By bioinformatics software, dual-luciferase reporter and RIP assays,
      we verified that miR-29a-3p was identified as a direct target of lncRNA-H19. RT
      PCR and western blot demonstrated that down-regulated lncRNA-H19 could affect the
      expression of miR-29a-3p targeting E2F1 with competitively binding miR-29a-3p.
      Furthermore, transwell assays indicated that lncRNA-H19 knockdown inhibited cells
      migration and invasion, but this effect was attenuated by co-transfection of
      lncRNA-H19 siRNA and miR-29a-3p inhibitor. Over expression of E2F1 could rescue
      lncRNA-H19 siRNA induced suppression on cell migration and invasion in ccRCC
      cells. Conclusions: These results show a possible competing endogenous RNAs
      regulatory network involving lncRNA-H19 regulates E2F1 expression by
      competitively sponging endogenous miR-29a-3p in ccRCC. This mechanism may
      contribute to a better understanding of ccRCC pathogenesis, and lncRNA-H19 may be
      further considered as a potential therapeutic target for ccRCC intervention.

PMID- 29214012
TI  - Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy
      in elderly allergic rhinitis patients: a randomized, double-blind placebo
      controlled trial.
AB  - Background: Allergen specific immunotherapy (AIT) in elderly patients is
      controversial, and there is still little evidence supporting the safety and
      efficacy of this treatment in this population. The study objective was to
      evaluate the safety and efficacy of AIT for house dust mite allergens in patients
      over 65 years of age with allergic rhinitis (AR) and a documented allergy to
      house dust mites. The primary endpoint was the change from baseline in the mean
      average adjusted symptom score (AAdSS) and the total combined rhinitis score
      (TCRS) difference in the least square means for the label compared to placebo.
      Methods: Fifty-eight AR elderly patients who were monosensitized to house dust
      mites were individually randomized in comparable numbers to one of two parallel
      groups with the following interventions: 2 years of perennial AIT using PURETHAL
      Mites or placebo. The symptoms and medication scores were presented as the AAdSS
      and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life
      questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen
      specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were
      monitored. The intent-to-treat population was analysed. Results: After 24 months
      of AIT, AAdSS significantly decreased from 4.27 +/- 1.58 to 1.82 +/- 0.71 (p <
      0.05). The TCRS was significantly decreased after 2 years of AIT. Serum-specific
      IgG4 against D. pteronyssinus, D. farinae, Der p1, and Der p2 increased during
      the AIT trial in the study group. The RQLQ score was significantly improved in
      patients who received AIT, from 1.86 (95% CI 1.51-1.78) to 1.26 (95% CI 1.09
      1.55). Two mild systemic anaphylactic reactions (degree I) were reported after
      injections in the active group during the AIT therapy. Conclusion: The DBPC trial
      showed AIT for house dust mite allergens was effective and safe in elderly
      patients with allergic rhinitis. Trial registration: This randomized, double
      blinded placebo-controlled (DBPC) trial was conducted at one centre
      (ClinicalTrials.gov no. NCT03209245).

PMID- 29214013
TI  - Prediction and prevention of allergy and asthma in EAACI journals (2016).
AB  - The European Academy of Allergy and Clinical Immunology (EAACI) owns three
      journals: Allergy, Pediatric Allergy and Immunology and Clinical and
      Translational Allergy. One of the major goals of EAACI is to support health
      promotion in which prevention of allergy and asthma plays a critical role and to
      disseminate the knowledge of allergy to all stakeholders including the EAACI
      junior members.

PMID- 29214014
TI  - Influence of perceived difficulty of cases on student osteopaths' diagnostic
      reasoning: a cross sectional study.
AB  - Background: Diagnostic reasoning refers to the cognitive processes by which
      clinicians formulate diagnoses. Despite the implications for patient safety and
      professional identity, research on diagnostic reasoning in osteopathy remains
      largely theoretical. The aim of this study was to investigate the influence of
      perceived task difficulty on the diagnostic reasoning of students osteopaths.
      Methods: Using a single-blinded, cross sectional study design, sixteen final year
      pre-registration osteopathy students diagnosed two standardized cases under two
      context conditions (complex versus control). Context difficulty was manipulated
      via verbal manipulation and case order was randomized and counterbalanced across
      subjects to ensure that each case was diagnosed evenly under both conditions
      (i.e. half of the subjects performed either case A or B first). After diagnosis,
      participants were presented with items (literal, inferred and filler) designed to
      represent analytical and non-analytical reasoning. Response time and error rate
      for each item were measured. A repeated measures analysis of variance (concept
      type x context) was performed to identify differences across conditions and make
      inferences on diagnostic reasoning. Results: Participants made significantly more
      errors when judging literal concepts and took significantly less time to
      recognize filler concepts in the complex context. No significant difference in
      ability to judge inferred concepts across contexts was found. Conclusions:
      Although speculative and preliminary, our findings suggest the perception of
      complexity led to an increased reliance on analytical reasoning at the detriment
      of non-analytical reasoning. To reduce the associated cognitive load, osteopathic
      educational institutions could consider developing the intuitive diagnostic
      capabilities of pre-registration students. Postgraduate mentorship opportunities
      could be considered to enhance the diagnostic reasoning of professional
      osteopaths, particularly recent graduates. Further research exploring the
      influence of expertise is required to enhance the validity of this study.

PMID- 29214015
TI  - Effect of spinal manipulative treatment on cardiovascular autonomic control in
      patients with acute low back pain.
AB  - Background: This study aimed to quantify the effect of spinal manipulative
      treatment (SMT) from an analysis of baroreflex, systolic blood pressure and heart
      rate variability (HRV) on patients with acute back pain. It was hypothesized that
      SMT would increase the parasympathetic cardiovascular autonomic control. Methods:
      Twenty-two patients with acute back pain were randomly divided into two groups:
      one receiving sham treatment (Sham) and the other receiving SMT. Recordings were
      completed during the first day and the seventh day, immediately before and after
      treatment on both days. ECG and systolic blood pressure were continuously
      recorded to compute cardiovascular variability and baroreflex sensitivity
      components. The perceived level of pain was measured with the numeric pain scale
      (NPS) 48 h before, just before and just after each treatment. The NPS ranged from
      0 to 100% (peak of pain before treatment). ECG and systolic blood pressure
      recordings were analyzed in time frequency domain using the Smoothed pseudo
      Wigner-Ville distribution. Results: Root mean square of the successive
      differences, high frequency power of the heart rate variability, and high
      frequency baroreflex sensitivity differences between post and pre tests were
      higher in the SMT group than in the Sham group (p < 0.01), whereas no differences
      were observed with the other heart rate variability components. Also, no
      differences were observed with the systolic blood pressure components. Although
      the estimated pain scale values decreased over time, no difference was observed
      between the SMT and Sham groups. Conclusions: This seems to be the first study to
      assess the effect of SMT on both heart rate variability and baroreflex
      sensitivity in patients with acute back pain. SMT can be seen to provoke an
      increase in parasympathetic control known to relate to a person's healthy state.
      Thus, cardiovascular variability analysis may be a useful tool for clinicians to
      quantify and objectify the beneficial effects of spinal manipulation treatment.

PMID- 29214016
TI  - Genotypic characterization of gentamicin and cephalosporin resistant Escherichia
      coli isolates from blood cultures in a Norwegian university hospital 2011-2015.
AB  - Background: Cephalosporin resistance in clinical E. coli isolates is increasing
      internationally. The increase has been caused by virulent and often multidrug
      resistant clones, especially the extended spectrum beta-lactamase (ESBL)
      producing E. coli clone O25b-ST131. Methods: In Norway, recommended empirical
      treatment of sepsis consists of gentamicin and penicillin combined, or a broad
      spectrum cephalosporin. To investigate if increased gentamicin and cephalosporins
      resistance rates in our hospital could be caused by specific clones, we conducted
      a retrospective study on E. coli blood culture isolates from 2011 through 2015.
      All E. coli isolates non-susceptible to gentamicin and/or third-generation
      cephalosporins were genotyped using multiple-locus variable-number of tandem
      repeat analysis (MLVA) and compared with antibiotic susceptible isolates. The
      frequency of the most common genes causing ESBL production (blaCTX-M, blaampC)
      was examined by Real-Time PCR. Results: A total of 158 cephalosporin and/or
      gentamicin resistant and 97 control isolates were differentiated into 126 unique
      MLVA types. Of these, 31% of the isolates belonged to a major MLVA cluster
      consisting of 41% of the gentamicin resistant and 35% of the cephalosporin
      resistant isolates. The majority (65/80 isolates) of this MLVA cluster contained
      MLVA types associated with the E. coli O25b-ST131 clone. Genes encoding CTX-M
      enzyme phylogroups 1 and 9 occurred in 65% and 19% of cephalosporin resistant
      isolates, respectively, whereas blaampC-CIT was identified in 3%. Conclusion: No
      local E. coli bacteraemia clone was identified. Antibiotic resistance was
      dispersed over a variety of genotypes. However, association with the
      international E. coli O25b-ST131 clone was frequent and may be an important
      driver behind increased resistance rates. Monitoring and preventing dissemination
      of these resistant clones are important for continued optimal treatment.

PMID- 29214017
TI  - Morphological bactericidal fast-acting effects of peracetic acid, a high-level
      disinfectant, against Staphylococcus aureus and Pseudomonas aeruginosa biofilms
      in tubing.
AB  - Background: The bactericidal effect of disinfectants against biofilms is
      essential to reduce potential endoscopy-related infections caused by
      contamination. Here, we investigated the bactericidal effect of a high-level
      disinfectant, peracetic acid (PAA), against Staphylococcus aureus and Pseudomonas
      aeruginosa biofilm models in vitro. Methods: S. aureus and P. aeruginosa biofilms
      were cultured at 35  degrees C for 7 days with catheter tubes. The following high
      level disinfectants (HLDs) were tested: 0.3% PAA, 0.55% ortho-phthalaldehyde
      (OPA), and 2.0% alkaline-buffered glutaraldehyde (GA). Biofilms were exposed to
      these agents for 1-60 min and observed after 5 min and 30 min by transmission and
      scanning electron microscopy. A Student's t test was performed to compare the
      exposure time required for bactericidal effectiveness of the disinfectants.
      Results: PAA and GA were active within 1 min and 5 min, respectively, against S.
      aureus and P. aeruginosa biofilms. OPA took longer than 10 min and 30 min to act
      against S. aureus and P. aeruginosa biofilms, respectively (p < 0.01). Treatment
      with PAA elicited changes in cell shape after 5 min and structural damage after
      30 min. Conclusions: Amongst the HLDs investigated, PAA elicited the most rapid
      bactericidal effects against both biofilms. Additionally, treatment with PAA
      induced morphological alterations in the in vitro biofilm models, suggesting that
      PAA exerts fast-acting bactericidal effects against biofilms associated with
      endoscopy-related infections. These findings indicate that the exposure time for
      bactericidal effectiveness of HLDs for endoscope reprocessing in healthcare
      settings should be reconsidered.

PMID- 29214018
TI  - Transcriptional changes in mesenteric and subcutaneous adipose tissue from
      Holstein cows in response to plane of dietary energy.
AB  - Background: Dairy cows can readily overconsume dietary energy during most of the
      prepartum period, often leading to higher prepartal concentrations of insulin and
      glucose and excessive body fat deposition. The end result of these physiologic
      changes is greater adipose tissue lipolysis post-partum coupled with excessive
      hepatic lipid accumulation and compromised health. Although transcriptional
      regulation of the adipose response to energy availability is well established in
      non-ruminants, such regulation in cow adipose tissue depots remains poorly
      characterized. Results: Effects of ad-libitum access to high [HIGH; 1.62 Mcal/kg
      of dry matter (DM)] or adequate (CON; 1.35 Mcal/kg of DM) dietary energy for 8 wk
      on mesenteric (MAT) and subcutaneous (SAT) adipose tissue transcript profiles
      were assessed in non-pregnant non-lactating Holstein dairy cows using a 13,000
      sequence annotated bovine oligonucleotide microarray. Statistical analysis
      revealed 409 and 310 differentially expressed genes (DEG) due to tissue and diet.
      Bioinformatics analysis was conducted using the Dynamic Impact Approach (DIA)
      with the KEGG pathway database. Compared with SAT, MAT had more active biological
      processes related to adipose tissue accumulation (adiponectin secretion) and
      signs of pro-inflammatory processes due to adipose tissue expansion and
      macrophage infiltration (generation of ceramides). Feeding the HIGH diet led to
      changes in mRNA expression of genes associated with cell hypertrophy
      (regucalcin), activation of adipogenesis (phospholipid phosphatase 1), insulin
      signaling activation (neuraminidase 1) and angiogenesis (semaphorin 4G, plexin
      B1). Further, inflammation due to HIGH was underscored by mRNA expression changes
      associated with oxidative stress response (coenzyme Q3, methyltransferase),
      ceramide synthesis (N-acylsphingosine amidohydrolase 1), and insulin signaling
      (interferon regulatory factor 1, phosphoinositide-3-kinase regulatory subunit 1,
      retinoic acid receptor alpha). Activation of ribosome in cows fed HIGH indicated
      the existence of greater adipocyte growth rate (M-phase phosphoprotein 10, NMD3
      ribosome export adaptor). Conclusions: The data indicate that long-term ad
      libitum access to a higher-energy diet led to transcriptional changes in adipose
      tissue that stimulated hypertrophy and the activity of pathways associated with a
      slight but chronic inflammatory response. Further studies would be helpful in
      determining the extent to which mRNA results also occur at the protein level.

PMID- 29214020
TI  - A quick and selected overview of the expert panel on effective ways of investing
      in health.
AB  - The European Commission created the Expert Panel on Effective Ways of Investing
      in Health (EXPH) in 2012. The EXPH started its activities in July 2013 and ended
      its first term in May 2016. A personal review of the Expert Panel contributions
      in its first term is provided.

PMID- 29214019
TI  - PKM2 is not required for colon cancer initiated by APC loss.
AB  - Background: Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate
      kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss
      can promote cancer progression; however, PKM2 has been reported to be essential
      in other tumor contexts, including a proposed non-metabolic role in beta-catenin
      nuclear translocation. PKM2 is expressed in colon cancers where loss of the Apc
      tumor suppressor results in beta-catenin nuclear translocation and aberrant
      activation of the canonical Wnt signaling pathway. Whether PKM2 is required in
      this colon cancer context has not been investigated. Results: Colon tumorigenesis
      was induced in mice harboring conditional Apc and Pkm2 alleles, and tumor
      progression was monitored by serial colonoscopy. PKM2 deletion had no effect on
      overall survival, the number of mice that developed tumors, or the number of
      tumors that developed per animal. Immunohistochemical analysis demonstrated PKM2
      expression in wild-type tumors and the expected loss of PKM2 expression in tumors
      from Pkm2 conditional mice. Loss of PKM2 resulted in pyruvate kinase M1
      expression but had no effect on nuclear beta-catenin staining. These findings are
      consistent with tumor growth and activated Wnt signaling despite PKM2 loss in
      this model. We also found a large fraction of human colon cancers had very low or
      undetectable levels of PKM2 expression. Conclusions: PKM2 is not required for Apc
      deficient colon cancer or for nuclear translocation of beta-catenin in Apc-null
      tumor cells. These findings suggest that PKM2 expression is not required for
      colon tumor formation or progression.

PMID- 29214021
TI  - A pilot study with early adolescents: dealing with diet, tobacco and air
      pollution using practical experiences and biological markers.
AB  - Background: Tobacco use and the Western diet are two of the most important and
      investigated topics in relation to adolescents' health. In addition, air
      pollution is a crucial subject for future generations. School is a key social
      environment that should promote healthy behaviors in children and adolescents. In
      this field many different programs have been conducted, with mixed results and
      effectiveness. Research data suggest that comprehensive and multicomponent
      approaches may have a greater effect on tobacco use and diet, especially when
      integrated into a community-wide approach. Methods: The present work describes a
      multi-area pilot study called "La Scuola della Salute" (the School of Health)
      with a focus on the methodological aspects of the intervention. In our study we
      assessed different web-based and practical experiences related to adolescents'
      smoking and dietary behaviors and awareness of smoke-related air pollution.
      Furthermore, to make adolescents more conscious of smoking and dietary behaviors,
      we conducted experiential workshops that addressed smoking and environmental
      pollution, food education, and lifestyle. Teachers and school administrators were
      involved in the project. Results: At baseline we investigated dietary habits,
      tobacco use, and individual and social characteristics by means of lifestyle
      questionnaires. In addition, we collected anthropometric parameters and
      performance indicators such as exhaled carbon monoxide and urinary fructose to
      assess smoking and nutrition habits. At the end of the intervention lifestyle
      questionnaire and biological markers were collected again: knowledge about these
      topics was significantly improved, and the urinary fructose was able to estimate
      the levels of obesity in the classes. Conclusions: The integrated approach,
      combined with the use of biological markers, could be an innovative approach to
      the promotion of healthy lifestyles among adolescents, but further research is
      needed.

PMID- 29214022
TI  - Advancing our understanding of the neurobiology of anorexia nervosa: translation
      into treatment.
AB  - A wealth of studies has investigated the neurobiological underpinnings of
      anorexia nervosa. In our letter to the editor, we point to a number of ways in
      which the advances in our understanding of the neurobiology of anorexia nervosa -
      focusing on neuroimaging studies of brain structure and function - can be
      translated into treatment. We point to how such advances can: inform
      psychological treatment, be implemented in psychoeducation, point to novel
      therapeutic targets, lead to the identification of biomarkers, and expand our
      vocabulary for how we think and talk about anorexia nervosa.

PMID- 29214023
TI  - Assessment and clinical management of bone disease in adults with eating
      disorders: a review.
AB  - Aim: To review current medical literature regarding the causes and clinical
      management options for low bone mineral density (BMD) in adult patients with
      eating disorders. Background: Low bone mineral density is a common complication
      of eating disorders with potentially lifelong debilitating consequences.
      Definitive, rigorous guidelines for screening, prevention and management are
      lacking. This article intends to provide a review of the literature to date and
      current options for prevention and treatment. Methods: Current, peer-reviewed
      literature was reviewed, interpreted and summarized. Conclusion: Any patient with
      lower than average BMD should weight restore and in premenopausal females,
      spontaneous menses should resume. Adequate vitamin D and calcium supplementation
      is important. Weight-bearing exercise should be avoided unless cautiously
      monitored by a treatment team in the setting of weight restoration. If a patient
      has a Z-score less than expected for age with a high fracture risk or likelihood
      of ongoing BMD loss, physiologic transdermal estrogen plus oral progesterone,
      bisphosphonates (alendronate or risedronate) or teriparatide could be considered.
      Other agents, such as denosumab and testosterone in men, have not been tested in
      eating-disordered populations and should only be trialed on an empiric basis if
      there is a high clinical concern for fractures or worsening bone mineral density.
      A rigorous peer-based approach to establish guidelines for evaluation and
      management of low bone mineral density is needed in this neglected subspecialty
      of eating disorders.

PMID- 29214024
TI  - Calcium-dependent ultrasound stimulation of secretory events from pancreatic beta
      cells.
AB  - Background: Our previous studies have indicated that ultrasound can stimulate the
      release of insulin from pancreatic beta cells, providing a potential novel
      treatment for type 2 diabetes. The purpose of this study was to explore the
      temporal dynamics and Ca2+-dependency of ultrasound-stimulated secretory events
      from dopamine-loaded pancreatic beta cells in an in vitro setup. Methods: Carbon
      fiber amperometry was used to detect secretion from INS-1832/13 beta cells in
      real time. The levels of released insulin were also measured in response to
      ultrasound treatment using insulin-specific ELISA kit. Beta cells were exposed to
      continuous wave 800 kHz ultrasound at intensities of 0.1 W/cm2, 0.5 W/cm2 and 1
      W/cm2 for several seconds. Cell viability tests were done with trypan blue dye
      exclusion test and MTT analysis. Results: Carbon fiber amperometry experiments
      showed that application of 800 kHz ultrasound at intensities of 0.5 and 1 W/cm2
      was capable of stimulating secretory events for durations lasting as long as the
      duration of the stimulus. Furthermore, the amplitude of the detected peaks was
      reduced by 64% (p < 0.01) when extracellular Ca2+ was chelated with 10 mM EGTA in
      cells exposed to ultrasound intensity of 0.5 W/cm2. Measurements of released
      insulin in response to ultrasound stimulation showed complete inhibition of
      insulin secretion by chelating extracellular Ca2+ with 10 mM EGTA (p < 0.01).
      Viability studies showed that 800 kHz, 0.5 W/cm2 ultrasound did not cause any
      significant effects on viability and metabolic activity in cells exposed to
      ultrasound as compared to sham-treated cells. Conclusions: Our results
      demonstrated that application of ultrasound was capable of stimulating the
      release of insulin from pancreatic beta cells in a safe, controlled and Ca2+
      dependent manner.

PMID- 29214025
TI  - Are we missing opportunities? Physiotherapy and physical activity promotion: a
      cross-sectional survey.
AB  - Background: Physical activity (PA) promotion in healthcare is an important
      strategy for increasing PA levels. Physiotherapists are well-positioned to
      promote PA, however no studies have investigated PA promotion by physiotherapists
      Australia-wide. Methods: An online survey of practicing Australian
      physiotherapists was conducted to investigate knowledge of the Australian
      Physical Activity and Sedentary Behaviour (PASB) guidelines and factors
      associated with increased promotion frequency. Participants were asked to state
      the PASB guidelines and a 4-component scoring system was used to measure
      knowledge. Multivariate logistic regression analysis was conducted to assess
      factors associated with frequency of promotion. Results: 257 Australian
      physiotherapists completed the survey. Only 10% were able to accurately state the
      PASB guidelines and 54% reported promoting PA to 10 or more patients per month.
      Males were nearly three times more likely than females to promote PA to 10 or
      more patients per month (OR 2.68, 95% CI 1.25-5.74). Those who lacked counselling
      skills and felt PA promotion wouldn't change their patients' behaviour were much
      less likely to promote PA. Conclusion: Australian physiotherapists have poor
      knowledge of the Australian PASB guidelines and infrequently promote PA.
      Education and training in PA counselling and behaviour change strategies is
      indicated to enhance PA promotion by Australian physiotherapists.

PMID- 29214026
TI  - Evaluating treatment outcomes and durations among cases of smear-positive
      pulmonary tuberculosis in Yemen: a prospective follow-up study.
AB  - Background: Evaluating outcomes after tuberculosis (TB) treatment can help
      identify the primary reasons for treatment success or failure. However, Yemen has
      a treatment success rate that remains below the World Health Organization's
      target. This study aimed to identify factors that were associated with
      unsuccessful treatment and prolonged treatment (>1 year). Method: Newly diagnosed
      cases of smear-positive pulmonary TB were prospectively followed at two centers
      (Taiz and Alhodidah, Yemen) between April 2014 and March 2015. Standardized forms
      were used to obtain information from the patients regarding their socio
      demographic and clinical characteristics, treatment duration, and TB-related
      information. Multivariate logistic regression analyses were performed to identify
      factors that were associated with unsuccessful treatment and prolonged treatment
      (>1 year). Results: The study included data from 273 cases of newly diagnosed TB,
      with treatment being successful in 227 cases (83.1%) and unsuccessful in 46 cases
      (16.9%). Among the 46 patients with unsuccessful treatment, 29 patients (10.6%)
      stopped treatment, 6 patients (2.2%) transferred to another facility, 6 patients
      (2.2%) experienced treatment failure, and 5 patients (1.8%) died. The
      multivariate logistic regression analyses revealed that unsuccessful treatment
      was associated with female sex, illiterate status, and the presence of
      comorbidities. Prolonged treatment durations were associated with living in a
      rural area, smoking, chewing khat, a cough that lasted for >3 weeks at the
      beginning of treatment, and bilateral cavities during radiography. Conclusion:
      These results confirm that the treatment success rate in Yemen is lower than the
      World Health Organization's target for smear-positive pulmonary tuberculosis.
      Targeting the risk factors that we identified may help improve treatment
      outcomes. Furthermore, it may not be prudent to re-treat patients using first
      line TB drugs after an initial treatment failure.

PMID- 29214027
TI  - To what extent do prescribing practices for hypertension in the private sector in
      Zimbabwe follow the national treatment guidelines? An analysis of insurance
      medical claims.
AB  - Background: Hypertension is the most prevalent cardiovascular disease in
      Zimbabwe. The prevalence of Hypertension in the country is above 30% regardless
      of the cut off used. Currently, majority of patients in Zimbabwe seek health care
      from the private sector due to limited government funding for the public health
      sector. However, Standard treatment guidelines for hypertension are only
      available in the public sector and are optional in the private sector. This study
      assesses compliance of private sector prescribing to Standard Treatment
      guidelines for hypertension. Methods: We reviewed hypertension prescription
      claims to a private health insurance company in Zimbabwe for the period Jan 1-Dec
      31 2015. We used the last prescription claimed in the year on the assumption that
      it represented the patient's current treatment. Prescription data was analyzed by
      comparing medicines prescribed to those recommended in the Zimbabwe 7th Essential
      Medicines List and Standard Treatment Guidelines 2015. We used Microsoft Excel(c)
      2010 to conduct the analysis. Results: A total of 1019 prescriptions were
      reviewed. Most patients were either on mono or dual therapy (76%). The mostly
      prescribed class of antihypertensive as first line were Angiotensin Converting
      Enzyme Inhibitors /Angiotensin Receptor Blockers. Regardless of whether they were
      being used as first, second or third line this class of antihypertensives emerged
      as the most prescribed (639 times). Only 358 (35%) prescriptions were compliant
      with standard treatment guidelines; the rest (661) did not meet several criteria.
      Areas of non-compliance included use of second line medicines as first line,
      failure to consider patient characteristics when prescribing, use of
      contraindicated medicines for certain patients, clinically significant
      interactions among prescribed medicines and illogical combinations that
      predispose patients to toxicity. Conclusion: The poor compliance to standard
      treatment guidelines observed in our study indicates need to improve prescription
      practices for Hypertension in the private sector in Zimbabwe for its cost
      effective management among the covered patients. However, further investigation
      is needed to understand the drivers of the prescribing habits and the non
      compliance to the Essential Medicines List and Standard Treatment guidelines
      observed. This will enable design of appropriate educational, managerial and
      economic interventions to improve compliance.

PMID- 29214028
TI  - Reprogramming of a defense signaling pathway in rough lemon and sweet orange is a
      critical element of the early response to 'Candidatus Liberibacter asiaticus'.
AB  - Huanglongbing (HLB) in citrus infected by Candidatus Liberibacter asiaticus
      (CLas) has caused tremendous losses to the citrus industry. No resistant
      genotypes have been identified in citrus species or close relatives. Among citrus
      varieties, rough lemon (Citrus jambhiri) has been considered tolerant due to its
      ability to produce a healthy flush of new growth after infection. The difference
      between tolerance and susceptibility is often defined by the speed and intensity
      of a plant's response to a pathogen, especially early defense responses. RNA-seq
      data were collected from three biological replicates of CLas- and mock-inoculated
      rough lemon and sweet orange at week 0 and 7 following infection. Functional
      analysis of the differentially expressed genes (DEGs) indicated that genes
      involved in the mitogen activated protein kinase (MAPK) signaling pathway were
      highly upregulated in rough lemon. MAPK induces the transcription of WRKY and
      other transcription factors which potentially turn on multiple defense-related
      genes. A Subnetwork Enrichment Analysis further revealed different patterns of
      regulation of several functional categories, suggesting DEGs with different
      functions were subjected to reprogramming. In general, the amplitude of the
      expression of defense-related genes is much greater in rough lemon than in sweet
      orange. A quantitative disease resistance response may contribute to the durable
      tolerance level to HLB observed in rough lemon.

PMID- 29214029
TI  - Comparative associations between anthropometric and bioelectric impedance
      analysis derived adiposity measures with blood pressure and hypertension in
      India: a cross-sectional analysis.
AB  - Background: The utility of bioelectrical impedance analysis (BIA) derived
      adiposity measures as compared to anthropometric measures for the assessment of
      adiposity-related health risk is not clear. We aimed to clarify the relationships
      of BIA and anthropometric derived adipose measures with blood pressure and
      hypertension, and to compare the discriminative ability of the respective
      measures for hypertension. Methods: We used baseline data collected between 2015
      and 2016 from the Indian Study on Health of Adults (ISHA), an ongoing population
      based cohort study in India (N = 5990; age 30-69 years). We examined and compared
      the associations and discriminative ability between anthropometric (body mass
      index, waist circumference, hip circumference, waist-hip ratio, waist-height
      ratio) and BIA (whole body and trunk fat percentage) derived adiposity measures
      with blood pressure components (systolic pressure, diastolic pressure, pulse
      pressure, mean arterial pressure, mid-blood pressure) and hypertension. Results:
      Regardless of whether the adiposity measure was derived from BIA or
      anthropometry, all were strongly and positively associated with blood pressure
      and hypertension. For both men and women, the magnitude of association of BIA
      measures with blood pressure and hypertension were comparable to those of
      anthropometric measures. Further, the ability of BIA derived adiposity measures
      to distinguish between those with and without hypertension was similar to the
      discriminative ability of anthropometric measures. Conclusions: As compared to
      simple anthropometric measures, BIA derived estimates of adiposity provide no
      apparent advantage in the assessment of blood pressure and hypertension. The
      observed similarities between adiposity measures suggest that simple
      anthropometrics may be sufficient to assess adiposity and adiposity-related
      risks.

PMID- 29214030
TI  - Prevalence and predictors of overweight and obesity among school-aged children in
      urban Ghana.
AB  - Background: Childhood overnutrition is a serious public health problem, with
      consequences that extend into adulthood. The aim of this study was to determine
      the prevalence and determinants of overweight and obesity among school-age
      children in two urban settings in Ghana. Methods: This cross-sectional study
      involved 3089 children (9-15 years) recruited between December 2009 and February
      2012 in Accra and Kumasi, Ghana. Socio-demographic, dietary, and physical
      activity data were collected using pretested questionnaires. BMI-for-age z-scores
      were used to categorize anthropometric data of the children as thin, normal, or
      overweight/obese. Determinants of overweight were examined using multiple
      logistic regressions. Results: Seventeen percent of children were overweight or
      obese. Children who reported lower participation (< 3 times/week) in sports
      activity were 44% more likely to be overweight or obese (AOR = 1.44; 95% CI:
      1.07, 1.94). Maternal tertiary education (AOR = 1.91, 95% CI: 1.07, 3.42), higher
      household socioeconomic status (AOR = 1.56, 95% CI: 1.18, 2.06), and attending
      private school (AOR = 1.74, 95% CI: 1.31, 2.32) were also associated with
      elevated risk of overweight and obesity. Conclusions: Physical inactivity is a
      modifiable independent determinant of overweight or obesity among Ghanaian school
      aged children. Promoting and supporting a physically active lifestyle in this
      population is likely to reduce risk of childhood overnutrition.

PMID- 29214031
TI  - PARP inhibitors as potential therapeutic agents for various cancers: focus on
      niraparib and its first global approval for maintenance therapy of gynecologic
      cancers.
AB  - Poly (ADP-ribose) polymerases (PARPs) are an important family of nucleoproteins
      highly implicated in DNA damage repair. Among the PARP families, the most studied
      are PARP1, PARP2 and PARP 3. PARP1 is found to be the most abundant nuclear
      enzyme under the PARP series. These enzymes are primarily involved in base
      excision repair as one of the major single strand break (SSB) repair mechanisms.
      Being double stranded, DNA engages itself in reparation of a sub-lethal SSB with
      the aid of PARP. Moreover, by having a sister chromatid, DNA can also repair
      double strand breaks with either error-free homologous recombination or error
      prone non-homologous end-joining. For effective homologous recombination repair,
      DNA requires functional heterozygous breast cancer genes (BRCA) which encode
      BRCA1/2. Currently, the development of PARP inhibitors has been one of the
      promising breakthroughs for cancer chemotherapy. In March 2017, the United States
      Food and Drug Administration (FDA) approved niraparib for maintenance therapy of
      recurrent gynecologic cancers (epithelial ovarian, primary peritoneal and
      fallopian tube carcinomas) which are sensitive to previous platinum based
      chemotherapy irrespective of BRCA mutation and homologous recombination
      deficiency status. It is the third drug in this class to receive FDA approval,
      following olaparib and rucaparib and is the first global approval for maintenance
      therapy of the aforementioned cancers. Niraparib preferentially blocks both PARP1
      and PARP2 enzymes. The daily tolerated dose of niraparib is 300 mg, above which
      dose limiting grade 3 and 4 toxicities were observed. In combination with
      humanized antibody, pembrolizumab, it is also under investigation for those
      patients who have triple negative breast cancer. By and large, there are several
      clinical trials that are underway investigating clinical efficacy and safety, as
      well as other pharmacokinetic and pharmacodynamic profiles of this drug for
      various malignancies.

PMID- 29214032
TI  - New therapies for advanced, recurrent, and metastatic endometrial cancers.
AB  - Endometrial cancer is the most common gynecologic malignancy in the United
      States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women
      were diagnosed with endometrial cancer, and approximately 11,000 died from this
      disease. From 1987 to 2008, there was a 50% increase in the incidence of
      endometrial cancer, with an approximate 300% increase in the number of associated
      deaths. Although there are many chemotherapeutic and targeted therapy agents
      approved for ovarian, fallopian tube and primary peritoneal cancers, since the
      1971 approval of megestrol acetate for the palliative treatment of advanced
      endometrial cancer, only pembrolizumab has been Food and Drug Administration
      (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair
      deficient (dMMR) endometrial cancer; this highlights the need for new therapies
      to treat advanced, recurrent, metastatic endometrial cancer. In this review, we
      discuss current and emerging treatment options for endometrial cancer, including
      chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute
      (NCI) and others are now focusing their efforts on the design of scientifically
      rational targeted therapy and immunotherapy trials for specific molecular
      phenotypes of endometrial cancer. This is essential for the advancement of cancer
      care for women, which is threatened by a severe enrollment decline of
      approximately 80% for gynecologic oncology clinical trials.

PMID- 29214034
TI  - Identification of biomarkers of response to abatacept in patients with SLE using
      deconvolution of whole blood transcriptomic data from a phase IIb clinical trial.
AB  - Objective: To characterise patients with active SLE based on pretreatment gene
      expression-defined peripheral immune cell patterns and identify clusters enriched
      for potential responders to abatacept treatment. Methods: This post hoc analysis
      used baseline peripheral whole blood transcriptomic data from patients in a phase
      IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were
      used with a published deconvolution algorithm to identify immune cell proportions
      in patient samples, and unsupervised consensus clustering was generated. Efficacy
      data were re-analysed. Results: Patient data (n=144: abatacept: n=98; placebo:
      n=46) were grouped into four main clusters (C) by predominant characteristic
      cells: C1-neutrophils; C2-cytotoxic T cells, B-cell receptor-ligated B cells,
      monocytes, IgG memory B cells, activated T helper cells; C3-plasma cells,
      activated dendritic cells, activated natural killer cells, neutrophils; C4
      activated dendritic cells, cytotoxic T cells. C3 had the highest baseline total
      British Isles Lupus Assessment Group (BILAG) scores, highest antidouble-stranded
      DNA autoantibody levels and shortest time to flare (TTF), plus trends in favour
      of response to abatacept over placebo: adjusted mean difference in BILAG score
      over 1 year, -4.78 (95% CI -12.49 to 2.92); median TTF, 56 vs 6 days; greater
      normalisation of complement component 3 and 4 levels. Differential improvements
      with abatacept were not seen in other clusters, except for median TTF in C1 (201
      vs 109 days). Conclusions: Immune cell clustering segmented disease severity and
      responsiveness to abatacept. Definition of immune response cell types may inform
      design and interpretation of SLE trials and treatment decisions. Trial
      registration number: NCT00119678; results.

PMID- 29214035
TI  - Cardiovascular risk profiles in a lupus cohort: what do different calculators
      tell us?
AB  - Background: Cardiovascular disease (CVD) is the leading cause of death worldwide
      and this risk is increased in patients with SLE who may not conform to
      traditional cardiovascular risk profiles. Aims: To determine the prevalence of
      high CVD risk among patients with SLE calculated using different risk
      calculators, and to characterise those identified as high risk. Methods: A cross
      sectional analysis to estimate CVD risk using the Framingham Risk Equation
      (Framingham score) and an SLE-specific CVD risk equation (SLE score) was
      undertaken using data from a single centre cohort. The characteristics of
      patients identified as 'high risk' by the SLE score only (the 'missed group')
      were compared with those identified by the Framingham score (the 'conventional
      group'). Results: 146 patients were included; 22 (15%) and 44 (30%) were
      determined to be at 'high risk' based on the Framingham and SLE scores,
      respectively. Patients in the 'missed group' were less likely to have traditional
      risk factors and were more likely to be female (81% vs 50%; p=0.03), younger
      (mean age 54 vs 69 years p<0.01) and have lower systolic blood pressure (132 vs
      143 mm Hg; p=0.05). Of those deemed high risk, only a minority were treated to
      target blood pressure and lipid levels. Conclusions: A large proportion of
      patients with SLE could be re-classified as high risk using a formula that
      incorporates SLE disease-related parameters. These patients have different
      profiles to those identified using a conventional risk model. Optimal CVD risk
      assessment and management warrants further attention in SLE.

PMID- 29214033
TI  - Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell
      lymphoma.
AB  - Objective: Determinants of the increased risk of diffuse large B-cell lymphoma
      (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide
      association study (GWAS), we assessed whether certain lupus-related single
      nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS
      data on European Caucasians from the International Lymphoma Epidemiology
      Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general
      population controls. Data were pooled in a random-effects meta-analysis. Results:
      Among the 28 SLE-related SNPs investigated, the two most convincingly associated
      with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome
      20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE
      risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01
      to 1.36, p=0.0362). Of additional possible interest were rs2205960 and
      rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis
      factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95%
      CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene)
      risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data
      suggest several plausible genetic links between DLBCL and SLE.

PMID- 29214037
TI  - Correlation of hypogammaglobulinaemia with proteinuria, and the relationship
      between hypogammaglobulinaemia and infection in active lupus nephritis.
AB  - Objective: To evaluate hypogammaglobulinaemia and risk of serious infectious
      adverse events in active lupus nephritis. Methods: The Abatacept and
      Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared
      abatacept with placebo in participants with lupus nephritis undergoing treatment
      with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were
      assessed prior to initiation of treatment and throughout the trial.
      Hypogammaglobulinaemia was defined as IgG <450 mg/dL. Results:
      Hypogammaglobulinaemia was observed in 16/102 (15.7%) participants prior to
      initiation of induction therapy for active lupus nephritis. Participants with
      nephrotic range proteinuria were more likely to have hypogammaglobulinaemia, and
      serum IgG levels were inversely correlated with urine protein to creatinine ratio
      (r=-0.42, p<0.0001). Following initiation of treatment for active lupus
      nephritis, additional participants developed hypogammaglobulinaemia by weeks 2-4.
      Serum IgG levels then increased, and all but one participant had serum IgG >=450
      mg/dL at 24 weeks. Hypogammaglobulinaemia was not associated with an increased
      risk of serious infectious adverse events. Conclusions: In active lupus nephritis
      in ACCESS, hypogammaglobulinaemia was common and inversely correlated with
      proteinuria. Serum IgG levels were lowest in the weeks immediately following
      initiation of induction therapy, and subsequently improved by 24 weeks.
      Hypogammaglobulinaemia was not associated with serious infectious adverse events.
      Trial registration: 

PMID- 29214036
TI  - Strong viral associations with SLE among Filipinos.
AB  - Objectives: Epstein-Barr virus (EBV) is considered an important environmental
      factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino
      population is unknown. We tested associations between SLE, lupus-associated
      autoantibodies and seropositivity for EBV and other herpes viruses in the
      Filipino population. Methods: Sera from Filipino patients with SLE (n=233),
      unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221)
      were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex
      viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV
      nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping.
      Autoantibodies were detected by a bead-based multiplex assay. Results were
      analysed by Fisher's exact test, Student's t-test, chi2 test and one-way analysis
      of variance, as appropriate for the question. Results: Filipino patients with SLE
      had increased seroprevalence and elevated antibody concentrations against EBV
      viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated
      controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of
      EBV reactivation, was dramatically increased in patients with SLE compared with
      unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or
      unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar
      seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA
      seropositivity correlated with lupus-associated autoantibodies (p<0.001), most
      notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A
      (p<0.01). Patient and unrelated control sera reacted to the highly repetitive
      glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was
      identified in sera of patients with SLE and showed limited binding by FDR and
      control sera. Conclusions: Filipino patients with SLE have elevated prevalence
      and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens,
      along with altered anti-EBNA-1 specificities. EBV reactivation is more common
      among Filipino patients with SLE compared with healthy Filipinos and may
      contribute to SLE pathogenesis in this population.

PMID- 29214038
TI  - Cell-bound complement activation products in SLE.
AB  - Diagnosis of SLE is based on clinical manifestations and laboratory findings.
      Timely diagnosis and treatment are important to control disease activity and
      prevent organ damage. However, diagnosis is challenging because of the
      heterogeneity in clinical signs and symptoms, and also because the disease
      presents with alternating periods of flare and quiescence. As SLE is an
      autoimmune disease characterised by the formation of autoantibodies, diagnostic
      immunology laboratory tests for detecting and quantifying autoantibodies are
      commonly used for the diagnosis and classification of SLE. These include ANA,
      anti-double-stranded DNA antibodies and anti-Smith antibodies, together with
      other antibodies such as antiphospholipid or anti-Cq1. Complement proteins C3 and
      C4 are commonly measured in patients with SLE, but their serum levels do not
      necessarily reflect complement activation. Cell-bound complement activation
      products (CB-CAPs) are fragments formed upon complement activation that bind
      covalently to haematopoietic cells. This review focuses on the complement system
      and, in particular, on CB-CAPs as biomarkers for the diagnosis and monitoring of
      SLE, vis-a-vis complement proteins and other biomarkers of complement activation.

PMID- 29214039
TI  - Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian
      families.
AB  - Background: To date, 43 types of Spinocerebellar Ataxias (SCAs) have been
      identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG
      repeat tract within the corresponding gene. Ethnic and geographic differences are
      evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the
      clinical phenotype and molecular genetics of the SCAs are available from the
      African continent. Established studies mostly concern the South African
      populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7
      mutation in South Africa (SA) has been found almost exclusively in families of
      indigenous Black African ethnic origin. Objective: To present the results of the
      first clinical description of seven Zambian families presenting with autosomal
      dominant SCA, as well as the downstream molecular genetic analysis of a subset of
      these families. Methods: The study was undertaken at the University Teaching
      Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating
      Scale derived from the modified international ataxia rating scale. Molecular
      genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was
      performed at the National Health Laboratory Service at Groote Schuur Hospital and
      the Division of Human Genetics, University of Cape Town, SA. The clinical and
      radiological features were evaluated in seven families with autosomal dominant
      cerebellar ataxia. Molecular genetic analysis was completed on individuals
      representing three of the seven families. Results: All affected families were
      ethnic Zambians from various tribes, originating from three different regions of
      the country (Eastern, Western and Central province). Thirty-four individuals from
      four families had phenotypic features of SCA7. SCA7 was confirmed by molecular
      testing in 10 individuals from 3 of these families. The age of onset of the
      disease varied from 12 to 59 years. The most prominent phenotypic features in
      these families were gait and limb ataxia, dysarthria, visual loss, ptosis,
      ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected
      members of the SCA7 families had progressive macular degeneration and cerebellar
      atrophy. All families displayed marked anticipation of age at onset and rate of
      symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56
      repeats. Three additional families were found to have clinical phenotypes
      associated with autosomal dominant SCA, however, DNA was not available for
      molecular confirmation. The age of onset of the disease in these families varied
      from 19 to 53 years. The most common clinical picture in these families included
      a combination of cerebellar symptoms with slow saccadic eye movements, peripheral
      neuropathy, dementia and tremor. Conclusion: SCA is prevalent in ethnic Zambian
      families. The SCA7 families in this report had similar clinical presentations to
      families described in other African countries. In all families, the disease had
      an autosomal dominant pattern of inheritance across multiple generations. All
      families displayed anticipation of both age of onset and the rate of disease
      progression. Further clinical and molecular investigations of the inherited
      ataxias in a larger cohort of patients is important to understand the natural
      history and origin of SCAs in the Zambian population.

PMID- 29214040
TI  - The smallest de novo 20q11.2 microdeletion causing intellectual disability and
      dysmorphic features.
AB  - The 20q11.2 microdeletion is a rare chromosomal aberration characterized by
      intellectual disability (ID), motor developmental delay, neonatal feeding
      problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl
      with a 1.2 Mb microdeletion of 20q11.2 showed ID, motor developmental delay, and
      distinctive facial features without feeding problems. The deleted region was
      identified by array-based comparative genomic hybridization and is the smallest
      reported for a 20q11.2 microdeletion.

PMID- 29214041
TI  - From a mouse: systematic analysis reveals limitations of experiments testing
      interventions in Alzheimer's disease mouse models.
AB  - The increasing prevalence of Alzheimer's disease (AD) poses a considerable socio
      economic challenge. Decades of experimental research have not led to the
      development of effective disease modifying interventions. A deeper understanding
      of in vivo research might provide insights to inform future in vivo research and
      clinical trial design. We therefore performed a systematic review and meta
      analysis of interventions tested in transgenic mouse models of AD. We searched
      electronically for publications testing interventions in transgenic models of AD.
      We extracted data for outcome, study characteristics and reported study quality
      and calculated summary estimates of efficacy using random effects meta-analysis.
      We identified 427 publications describing 357 interventions in 55 transgenic
      models, involving 11,118 animals in 838 experiments. Of concern, reported study
      quality was relatively low; fewer than one in four publications reported the
      blinded assessment of outcome or random allocation to group and no study reported
      a sample size calculation. Additionally, there were few data for any individual
      intervention-only 16 interventions had outcomes described in 5 or more
      publications. Finally, "trim and fill" analyses suggested one in seven
      pathological and neurobehavioural experiments remain unpublished. Given these
      historical weaknesses in the in vivo modelling of AD in transgenic animals and
      the identified risks of bias, clinical trials that are based on claims of
      efficacy in animals should only proceed after a detailed critical appraisal of
      those animal data.

PMID- 29214042
TI  - Maternal weight in the postpartum: results from the Delta healthy sprouts trial.
AB  - Background: Excessive postnatal weight retention may pose a threat to a woman's
      health and future pregnancies. Women in the Lower Mississippi Delta (LMD) region
      of Mississippi suffer from among the highest rates of obesity in the U.S. and are
      more likely to gain an excessive amount of weight during pregnancy. The aim of
      this study was to determine if LMD women who received a lifestyle enhanced
      maternal, infant, and early childhood home visiting (MIECHV) curriculum had more
      favorable weight outcomes through 12-months postpartum compared to women who
      received a standard MIECHV curriculum. Methods: Delta Healthy Sprouts was a two
      arm, randomized, controlled, comparative impact trial. Pregnant women at least 18
      years of age, less than 19 weeks pregnant with a singleton pregnancy, and
      residing in the LMD region were recruited. On a monthly basis in the
      participant's home, the control arm (PAT) received the Parents as Teachers
      curriculum while the experimental arm (PATE) received a lifestyle enhanced
      Parents as Teachers curriculum. Pre-pregnancy body weight via self-report and
      maternal body weight at baseline (gestational month 4) and at every subsequent
      monthly visit through 12 months postpartum was measured. Linear mixed models were
      used to test for significant treatment, time, and treatment by time effects on
      postnatal weight outcomes. Results: Mean postnatal weight losses were 0.8 and 1.1
      kg at postnatal month (PM) 6 and PM 12, respectively, for PAT participants. Mean
      postnatal weight losses for PATE participants were 1.5 and 1.2 kg at PM 6 and PM
      12, respectively. Mean weight retention, based on pre-pregnancy weight, were 5.2,
      4.0, and 3.6 kg at PM 1, PM 6, and PM 12, respectively, for PAT participants.
      Mean weight retention for PATE participants were 6.3, 4.5, and 4.0 kg at PM 1, PM
      6, and PM 12, respectively. Significant effects were not found for treatment,
      time, or treatment by time. Conclusions: An enhanced MIECHV curriculum was not
      associated with more favorable postpartum weight outcomes when compared to a
      standard MIECHV curriculum in a cohort of LMD women during the 12 months
      following the birth of their infant. Trial registration: clinicaltrials.gov,
      NCT01746394. Registered 5 December 2012.

PMID- 29214043
TI  - Folic acid level and preterm birth among Sudanese women.
AB  - Background: Preterm birth (PTB) is the major health problem world-wide; there are
      few published studies on PTB and folic acid. Methods: The study was conducted to
      assess the serum level of folic acid in PTB. A case-control study was conducted
      at Saad Abualila maternity hospital (Khartoum, Sudan) during the period of March
      through December 2015. Women who delivered live singleton babies were dived in
      two groups; the cases were women who had PTB "delivery before completed 37weeks
      but after 24 weeks of pregnancy" and the controls were women who delivered at
      term (37-42 weeks). Medical and obstetrics history was gathered using
      questionnaire. Serum folic acid was measured. Results: One hundred and twelve (56
      in arm of the study) women were enrolled to the study. There was no significant
      difference between the cases and the controls in their age, parity, hemoglobin,
      body mass index, education and occupation. The median (interquartile) level of
      folic acid was significantly lower in the cases (PTB) than the level in the
      controls, 4.8(2.8-8.2) vs. 9.5(8.6-12.0) ng/ml. In binary regression, folic acid
      level was associated with lower risk of PTB (OR=0.64; 95%=0.53-0.77, P < 0.001).
      There was a significant positive correlation between gestational age and folic
      acid level (r = 0.447, P<0.001). Conclusion: Thus serum folic acid level was
      significantly lower in women with PTB. Folic acid level was associated with lower
      risk of PTB.

PMID- 29214044
TI  - Milk yield and kit development of four breeds of rabbit in Ibadan, Nigeria.
AB  - Background: Rabbit breeding with high performance imported ones would be of
      benefit for genetic diversity and improvement of performance in domestic rabbit
      breeds. The rearing of more productive rabbit breeds could be pathway to improve
      the productivity and reduce the production cost. Maternal nutritional status
      exert a great influence on reproductive functions of does, which may expand from
      conception, through gestation and parturition and development of kits to puberty.
      Methods: Four breeds of rabbit were evaluated for their parturition, weaning and
      pubertal differences among the rabbit population in Ibadan, Nigeria. The breed
      consist of Fauve De Bourgogne (FDB), Chinchilla (CHA), British Spot (BS) and New
      Zealand White (NZW) rabbits. A total of 60 bucks and 360 does consisting of 15
      bucks and 90 does per breed were mated in 6 mating cycles, three each of natural
      mating and artificial insemination. All does were synchronized for estrus with 20
      IU pregnant mare serum gonadotropin 48 h prior to mating. The does after
      parturition were assessed for milk yield (g) and kit survival rate (%) till
      weaning, weight changes of kits from birth to puberty. At puberty, the pubertal
      age (days) and weight (g) of the offspring were assessed. Result: Results
      obtained reveals that British Spot doe had highest milk yield among the breeds
      which significantly increased growth of kit and weight at weaning in British Spot
      rabbits. Survival rates of Chinchilla kits were significantly (p < 0.05) higher
      than Fauve de Bourgogne, British Spot and New Zealand White kits. Puberty
      attainment of the rabbits indicates that British spot does and Fauve de Bourgogne
      bucks are early maturing. Conclusion: Chinchilla shows high kit survivability and
      British spot has highest milk yield among the four breeds of rabbit.

PMID- 29214045
TI  - The rumen microbiome: an underexplored resource for novel antimicrobial
      discovery.
AB  - Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug
      resistant bacteria. The rumen microbiome presents an underexplored resource for
      the discovery of novel microbial enzymes and metabolites, including AMPs. Using
      functional screening and computational approaches, we identified 181 potentially
      novel AMPs from a rumen bacterial metagenome. Here, we show that three of the
      selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against
      numerous bacterial pathogens, including methicillin-resistant Staphylococcus
      aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of
      sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial
      membrane lipids and induced membrane permeability leading to cytoplasmic leakage.
      Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound
      infection elicited a significant reduction in bacterial counts, which was
      comparable to treatment with 2% mupirocin ointment. Our findings indicate that
      the rumen microbiome may provide viable alternative antimicrobials for future
      therapeutic application.

PMID- 29214046
TI  - High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status
      reveal common colorectal cancer consortia.
AB  - Colorectal cancer (CRC) remains the third most common cancer worldwide, with a
      growing incidence among young adults. Multiple studies have presented
      associations between the gut microbiome and CRC, suggesting a link with cancer
      risk. Although CRC microbiome studies continue to profile larger patient cohorts
      with increasingly economical and rapid DNA sequencing platforms, few common
      associations with CRC have been identified, in part due to limitations in
      taxonomic resolution and differences in analysis methodologies. Complementing
      these taxonomic studies is the newly recognized phenomenon that bacterial
      organization into biofilm structures in the mucus layer of the gut is a
      consistent feature of right-sided (proximal), but not left-sided (distal)
      colorectal cancer. In the present study, we performed 16S rRNA gene amplicon
      sequencing and biofilm quantification in a new cohort of patients from Malaysia,
      followed by a meta-analysis of eleven additional publicly available data sets on
      stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution
      analytical tool for species-level characterization. Results from the Malaysian
      cohort and the expanded meta-analysis confirm that CRC tissues are enriched for
      invasive biofilms (particularly on right-sided tumors), a symbiont with capacity
      for tumorigenesis (Bacteroides fragilis), and oral pathogens including
      Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis.
      Considered in aggregate, species from the Human Oral Microbiome Database are
      highly enriched in CRC. Although no detected microbial feature was universally
      present, their substantial overlap and combined prevalence supports a role for
      the gut microbiota in a significant percentage (>80%) of CRC cases.

PMID- 29214047
TI  - High-resolution profiling of the gut microbiome reveals the extent of Clostridium
      difficile burden.
AB  - Microbiome profiling through 16S rRNA gene sequence analysis has proven to be a
      useful research tool in the study of C. difficile infection (CDI); however, CDI
      microbiome studies typically report results at the genus level or higher, thus
      precluding identification of this pathogen relative to other members of the gut
      microbiota. Accurate identification of C. difficile relative to the overall gut
      microbiome may be useful in assessments of colonization in research studies or as
      a prognostic indicator for patients with CDI. To investigate the burden of C.
      difficile at the species level relative to the overall gut microbiome, we applied
      a high-resolution method for 16S rRNA sequence assignment to previously published
      gut microbiome studies of CDI and other patient populations. We identified C.
      difficile in 131 of 156 index cases of CDI (average abundance 1.78%), and 18 of
      211 healthy controls (average abundance 0.008%). We further detected substantial
      levels of C. difficile in a subset of infants that persisted over the first two
      to 12 months of life. Correlation analysis of C. difficile burden compared to
      other detected species demonstrated consistent negative associations with C.
      scindens and multiple Blautia species. These analyses contribute insight into the
      relative burden of C. difficile in the gut microbiome for multiple patient
      populations, and indicate that high-resolution 16S rRNA gene sequence analysis
      may prove useful in the development and evaluation of new therapies for CDI.

PMID- 29214048
TI  - Good vaccination practice: it all starts with a good vaccine storage temperature.
AB  - Background: Recent introduction of strategies to reduce antibiotic use in food
      animal production implies an increased use of vaccines in order to prevent the
      economic impact of several important diseases in swine. Good Vaccination Practice
      (GVP) is an overall approach on the swine farm aiming to obtain maximal efficacy
      of vaccination through good storage, preparation and finally correct application
      to the target animals. In order to have a better insight into GVP on swine farms
      and the vaccine storage conditions, a survey on vaccination practices was
      performed on a farmers' fair and temperatures in the vaccine storage
      refrigerators were measured during farm visits over a period of 1 year. Results:
      The survey revealed that knowledge on GVP, such as vaccine storage and handling,
      needle management and injection location could be improved. Less than 10% had a
      thermometer in their vaccine storage refrigerator on the moment of the visit.
      Temperature measurement revealed that only 71% of the measured refrigerators were
      in line with the recommended temperature range of +2  degrees C to +8  degrees C.
      Both below +2  degrees C and above +8  degrees C temperatures were registered
      during all seasons of the year. Compliance was lower during summer with an
      average temperature of 9.2  degrees C while only 43% of the measured temperatures
      were within the recommended range. Conclusions: The present study clearly showed
      the need for continuous education on GVP for swine veterinarians, swine farmers
      and their farm personnel in general and vaccine storage management in particular.
      In veterinary medicine, the correct storage of vaccines is crucial since both too
      low and too high temperatures can provoke damage to specific vaccine types.
      Adjuvanted killed or subunit vaccines can be damaged (e.g. structure of
      aluminiumhydroxide in adjuvans) by too low temperatures (below 0  degrees C),
      whereas lyophilized live vaccines are susceptible (e.g. loss of vaccine potency)
      to heat damage by temperatures above +8  degrees C. In conclusion, knowledge and
      awareness of GVP and vaccine storage conditions are crucial under practical field
      conditions in swine herds. Focus on a correct on-farm vaccine storage is part of
      the responsible veterinarians' guidance in order to obtain the required vaccine
      efficacy.

PMID- 29214049
TI  - Latent autoimmune diabetes of adulthood: case report.
AB  - Background: Primary care clinicians will see a higher incidence of type 2
      diabetes in adult patients, and the diagnosis and management of an initial
      presentation of type 1 diabetes can pose challenges to clinicians who see it less
      frequently. Symptoms of hyperglycemia and risk of ketoacidosis may be missed.
      Further, endocrine autoimmune disease can run together in patients and families.
      Case presentation: A 49-year-old Caucasian female with history of pituitary
      adenoma and Graves' disease with history of thyroid ablation presented in the
      outpatient setting due to hand tingling of her right middle finger that was worse
      in the mornings and improved throughout the day. She also complained of excessive
      thirst, finding herself drinking more water than usual and waking up in the night
      to urinate. There was no dysuria or haematuria, and no other neurologic symptoms.
      She did report feeling hungry. She had no family history of diabetes, normal body
      mass index of 21.7, and reported taking her thyroid replacement medication every
      day. The differential diagnosis for her thirst included dehydration, psychogenic
      polydipsia, diabetes mellitus, diabetes insipidus, and anxiety. The patient had
      normal vital signs and was well appearing; labs were ordered for her on her way
      home from clinic with no medications. Labs revealed a random blood glucose level
      of 249 mg/dL, normal renal function, a normal B12 of 996 pg/mL, and an elevated
      thyroid stimulating hormone level of 25.67 u[iU]/mL. On follow up with her
      primary care provider 5 days later, additional labs were drawn showing A1C of
      11.5%, 1+ ketonuria, a negative Acetest, and a normal basic metabolic panel,
      except for a fasting glucose of 248 mg/dL, and Free T3 of 2.42 pg/mL, and Free T4
      of 1.7 ng/dL. Islet cell antibodies and glutamic acid decarboxylase antibodies
      were both positive, consistent with type 1 diabetes. She was started on insulin
      and improved. Conclusion: Given the patient's age, this is a less common
      presentation of type 1 diabetes mellitus, as a part of polyglandular autoimmune
      syndrome type IIIa. It serves as a reminder that clinicians should remember that
      patients with one autoimmune disease (in this case, h/o Graves' disease) are at
      higher risk for diabetes and other endocrine autoimmune diseases and should be
      screened appropriately. Clinicians should keep latent type 1 diabetes in the
      differential in adulthood to ensure proper and timely treatment.

PMID- 29214050
TI  - Paternal phylogeographic structure of the brown bear (Ursus arctos) in
      northeastern Asia and the effect of male-mediated gene flow to insular
      populations.
AB  - Background: Sex-biased dispersal is widespread among mammals, including the brown
      bear (Ursus arctos). Previous phylogeographic studies of the brown bear based on
      maternally inherited mitochondrial DNA have shown intraspecific genetic
      structuring around the northern hemisphere. The brown bears on Hokkaido Island,
      northern Japan, comprise three distinct maternal lineages that presumably
      immigrated to the island from the continent in three different periods. Here, we
      investigate the paternal genetic structure across northeastern Asia and assess
      the connectivity among and within intraspecific populations in terms of male
      mediated gene flow. Results: We analyzed paternally inherited Y-chromosomal DNA
      sequence data and Y-linked microsatellite data of 124 brown bears from Hokkaido,
      the southern Kuril Islands (Kunashiri and Etorofu), Sakhalin, and continental
      Eurasia (Kamchatka Peninsula, Ural Mountains, European Russia, and Tibet). The
      Hokkaido brown bear population is paternally differentiated from, and lacked
      recent genetic connectivity with, the continental Eurasian and North American
      populations. We detected weak spatial genetic structuring of the paternal
      lineages on Hokkaido, which may have arisen through male-mediated gene flow among
      natal populations. In addition, our results suggest that the different dispersal
      patterns between male and female brown bears, combined with the founder effect
      and subsequent genetic drift, contributed to the makeup of the Etorofu Island
      population, in which the maternal and paternal lineages show different origins.
      Conclusions: Brown bears on Hokkaido and the adjacent southern Kuril Islands
      experienced different maternal and paternal evolutionary histories. Our results
      indicate that sex-biased dispersal has played a significant role in the
      evolutionary history of the brown bear in continental populations and in
      peripheral insular populations, such as on Hokkaido, the southern Kuril Islands,
      and Sakhalin.

PMID- 29214051
TI  - Cytochrome b5 protects photoreceptors from light stress-induced lipid
      peroxidation and retinal degeneration.
AB  - Lipid peroxides are generated by oxidative stress in cells, and contribute to
      ageing and neurodegenerative disease. The eye is at special risk for lipid
      peroxidation because photoreceptors possess amplified sensory membranes rich in
      peroxidation-susceptible polyunsaturated fatty acids. Light-induced lipid
      peroxidation in the retina contributes to retinal degeneration, and lipid
      peroxidation has been implicated in the progression of age-associated ocular
      diseases such as age-related macular degeneration (AMD). Here, we show that
      exposing Drosophila melanogaster to strong blue light induces oxidative stress
      including lipid peroxidation that results in retinal degeneration. Surprisingly,
      very young flies are resilient to this acute light stress, suggesting they
      possess endogenous neuroprotective mechanisms. While lipophilic antioxidants
      partially suppressed blue light-induced retinal degeneration in older flies, we
      find that overexpression of cytochrome b5 (Cyt-b5) completely suppressed both
      blue light-induced lipid peroxidation and retinal degeneration. Our data identify
      Cyt-b5 as a neuroprotective factor that targets light-induced oxidative damage,
      particularly lipid peroxidation. Cyt-b5 may function via supporting antioxidant
      recycling, thereby providing a strategy to prevent oxidative stress in ageing
      photoreceptors that would be synergistic with dietary antioxidant
      supplementation.

PMID- 29214052
TI  - Neuroprotective role of retinal SIRT3 against acute photo-stress.
AB  - SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as
      mitochondrial function. The retina is one of the highest energy-demanding
      tissues, in which the regulation of reactive oxygen species is critical to
      prevent retinal neurodegeneration. Although previous reports have demonstrated
      that SIRT3 is highly expressed in the retina and important in neuroprotection,
      function of SIRT3 in regulating reactive oxygen species in the retina is largely
      unknown. In this study, we investigated the role of retinal SIRT3 in a light
      induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that
      SIRT3 deficiency causes acute reactive oxygen species accumulation and
      endoplasmic reticulum stress in the retina after the light exposure, which leads
      to increased photoreceptor death, retinal thinning, and decreased retinal
      function. Using a photoreceptor-derived cell line, we revealed that reactive
      oxygen species were the upstream initiators of endoplasmic reticulum stress.
      Under SIRT3 knockdown condition, we demonstrated that decreased superoxide
      dismutase 2 activity led to elevated intracellular reactive oxygen species. These
      studies have helped to elucidate the critical role of SIRT3 in photoreceptor
      neuronal survival, and suggest that SIRT3 might be a therapeutic target for
      oxidative stress-induced retinal disorders.

PMID- 29214053
TI  - Severe carvedilol toxicity without overdose - caution in cirrhosis.
AB  - Background: Carvedilol is used in the management of hypertension, ischemic heart
      disease, heart failure and most recently, portal hypertension. It has been
      associated with improved outcomes regarding variceal bleeding, hepatic
      decompensation and death when compared to propranolol and endoscopic band
      ligation. The main cause of portal hypertension is cirrhosis and therefore
      carvedilol is increasingly used in these patients. Due to its extensive hepatic
      metabolism, carvedilol is contraindicated in severe hepatic impairment. However,
      there are no dosage adjustments in the manufacturer's labelling for mild to
      moderate hepatic impairment. Case presentation: We present a case of cardiogenic
      shock that occurred after carvedilol 25 mg orally was administered to a patient
      with cirrhosis. As there was no overdose, the diagnosis was based on clinical
      recognition of the toxidrome. The patient was successfully treated with glucagon
      5 mg bolus followed by infusion. Conclusions: Patients with cirrhosis represent a
      special at-risk group for beta blocker toxicity. The typical threshold for
      carvedilol toxicity in overdose is 50 mg but in patients with cirrhosis this is
      not applicable. Nurses and physicians need to recognize the toxidrome early.
      Hospitals where carvedilol is used in patients with cirrhosis should have
      glucagon in formulary at doses to treat toxicity (bolus and infusion). Finally,
      dose adjustment and slow uptitration of carvedilol in cirrhosis is recommended.

PMID- 29214054
TI  - Lifestyle modification practice and associated factors among diagnosed
      hypertensive patients in selected hospitals, South Ethiopia.
AB  - Background: Hypertension is one of the leading causes of disability and death in
      both developed and developing countries that need urgent strategies to implement
      interventions that control it. Appropriate lifestyle changes often called non
      pharmacological approaches that often overlooked are the corner stone of the
      prevention and control of hypertension. The aim of this study is to assess the
      practice of lifestyle modifications and associated factors among diagnosed
      hypertensive patients in Durame and Nigist Elleni Mohamed Memorial General
      Hospitals in southern Ethiopia. Methods: Facility-based cross-sectional study was
      conducted among 205 hypertensive patients in Durame and Nigist Elleni Mohamed
      Memorial General Hospitals in Sothern Nation and Nationality People
      Representative (SNNPR), from March 1-30 2016. Simple random sampling was used to
      select study subjects. Data were entered to Epidata 3.1 and exported to
      Statistical Package for Social Sciences (SPSS) version 20.0 for analysis. A
      binary Logistic regression model was fitted to determine independent predictors
      of lifestyle modifications among hypertensive patients. Adjusted odds ratio at
      95%CI was used to declaring the independent effect of each variable on the
      outcome variable. Result: The study revealed that only 56(27.3%) of the patients
      practiced recommended lifestyle modifications. The study found that age (Adjusted
      Odds Ratio [AOR] = 0.27, 95% Confidence Interval [CI]:0.13-0.61), educational
      status (AOR = 2.00,95% CI:1.33-6.75), monthly income (AOR = 2.46, 95% CI:1.32
      4.63), years since diagnosis (AOR = 2.48, 95%CI: 1.32-4.69), and co-morbidity
      (AOR = 0.28,95% CI: 0.13-0.61) were factors significantly associated with
      lifestyle modification practice (p < 0.05). Conclusion: Generally, lifestyle
      modification practices among hypertensive patients were low in this study.
      Therefore, Patients should be educated on the recommended lifestyle modifications
      that may help patients to control f their blood pressure.

PMID- 29214055
TI  - Integrative gene network analysis identifies key signatures, intrinsic networks
      and host factors for influenza virus A infections.
AB  - Influenza A virus, with the limited coding capacity of 10-14 proteins, requires
      the host cellular machinery for many aspects of its life cycle. Knowledge of
      these host cell requirements not only reveals molecular pathways exploited by the
      virus or triggered by the immune system, but also provides further targets for
      antiviral drug development. To uncover novel pathways and key targets of
      influenza infection, we assembled a large amount of data from 12 cell-based gene
      expression studies of influenza infection for an integrative network analysis. We
      systematically identified differentially expressed genes and gene co-expression
      networks induced by influenza infection. We revealed the dedicator of cytokinesis
      5 (DOCK5) played potentially an important role for influenza virus replication.
      CRISPR/Cas9 knockout of DOCK5 reduced influenza virus replication, indicating
      that DOCK5 is a key regulator for the viral life cycle. DOCK5's targets
      determined by the DOCK5 knockout experiments strongly validated the predicted
      gene signatures and networks. This study systematically uncovered and validated
      fundamental patterns of molecular responses, intrinsic structures of gene co
      regulation, and novel key targets in influenza virus infection.

PMID- 29214056
TI  - Strength in Numbers: an international consensus conference to develop a novel
      approach to care delivery for young adults with type 1 diabetes, the D1 Now
      Study.
AB  - Plain English summary: Many young adults with type 1 diabetes struggle with the
      day-to-day management of their condition. They often find it difficult to find
      the time to attend their clinic appointments and to meet with their diabetes
      healthcare team. Young adults living with type 1 diabetes are not routinely
      involved in research that may help improve health services other than being
      invited to take part in studies as research participants. A 3-day international
      conference was held in Galway in June 2016 called "Strength In Numbers: Teaming
      up to improve the health of young adults with type 1 diabetes". It aimed to bring
      together people from a broad variety of backgrounds with an interest in young
      adults with type 1 diabetes. Young people with type 1 diabetes came together with
      healthcare professionals, researchers, software developers and policy makers to
      come up with and agree on a new approach for engaging young adults with type 1
      diabetes with their health services and to improve how they manage their
      diabetes.The people involved in the conference aimed to reach agreement
      (consensus) on a fixed set of outcome measures called a core outcome set (COS)
      that the group would recommend future studies involving young adults with type 1
      diabetes to use, to suggest a new approach (intervention) for providing health
      services to young adults with type 1 diabetes, and to come up with health
      technology ideas that could help deliver the new intervention. Over the 3 days,
      this diverse international group of people that included young adults living with
      type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1
      possible health technology idea that could help with how the overall intervention
      could be delivered.Involving young adults living with type 1 diabetes in a 3-day
      conference along with other key groups is an effective method for coming up with
      a new approach to improve health services for young adults with type 1 diabetes
      and better support their self-management. Abstract: Background A 3-day
      international consensus meeting was hosted by the D1 Now study team in Galway on
      June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of
      young adults with type 1 diabetes". The aim of the meeting was to bring together
      young adults with type 1 diabetes, healthcare providers, policy makers and
      researchers to reach a consensus on strategies to improve engagement, self
      management and ultimately outcomes for young adults living with type 1 diabetes.
      Methods This diverse stakeholder group participated in the meeting to reach
      consensus on (i) a core outcome set (COS) to be used in future intervention
      studies involving young adults with type 1 diabetes, (ii) new strategies for
      delivering health services to young adults and (iii) potential digital health
      solutions that could be incorporated into a future intervention. Results A COS of
      8 outcomes and 3 key intervention components that aim to improve engagement
      between young adults with type 1 diabetes and service providers were identified.
      A digital health solution that could potentially compliment the intervention
      components was proposed. Conclusion The outputs from the 3-day consensus
      conference, that held patient and public involvement at its core, will help the
      research team further develop and test the D1 Now intervention for young adults
      with type 1 diabetes in a pilot and feasibility study and ultimately in a
      definitive trial. The conference represents a good example of knowledge exchange
      among different stakeholders for health research and service improvement.

PMID- 29214057
TI  - Primary rhegmatogenous retinal detachment with inferior retinal breaks
      postoperative prone positioning results: 1 day versus 7 days.
AB  - Background: To compare the primary anatomical outcome of pars plana vitrectomy,
      360 degrees  peripheral endolaser, and 15% octafluoropropane C3F8 gas tamponade
      in patients with uncomplicated rhegmatogenous detachment and inferior retinal
      breaks, after 24-h postoperative prone positioning to similar patients with 1
      week postoperative prone positioning. Methods: Records of 5500 patients who
      underwent pars plana vitrectomy between 2008 and 2015 were retrieved. Collected
      data included age, gender, number of retinal quadrants with retinal breaks,
      number of retinal breaks, macula status on presentation (attached or detached),
      phakic status (phakic, pseudophakic, or aphakic), and primary anatomical outcome
      (at 1 and 3 months post-operative). Results: 270 patients met the study inclusion
      criteria (78 females, and 192 males). In the 24-h positioning arm (183 patients),
      the overall anatomical success rate was 96.2% at 1 month and 83.6% at 3 months.
      In the 1-week positioning group (87 patients), the overall anatomical success
      rate was 93% at 1 month and 79% at 3 months. Both positioning groups did not show
      statistical difference in outcome at 1 month (p-value = 0.7) or at 3 months (p
      value = 0.39). Logistic regression analysis found that the number of retinal
      breaks correlates with the postoperative anatomical success at 3 months (odd
      ratio 0.8, p-value = 0.016). Conclusion: This short term retrospective study
      demonstrated that patients with uncomplicated rhegmatogenous retinal detachment
      due to inferior retinal breaks, who underwent pars plana vitrectomy, 360 degrees 
      endolaser, 15% C3F8 gas, and limited (24-h) prone positioning did not show
      statistical difference in the anatomical outcome (at 1, and 3 months) when
      compared with 1 week postoperative positioning. Larger prospective studies are
      warranted to further elucidate positioning role.

PMID- 29214059
TI  - Focused issue on interventional pulmonology.

PMID- 29214058
TI  - The design of reversible hydrogels to capture extracellular matrix dynamics.
AB  - The extracellular matrix (ECM) is a dynamic environment that constantly provides
      physical and chemical cues to embedded cells. Much progress has been made in
      engineering hydrogels that can mimic the ECM, but hydrogel properties are, in
      general, static. To recapitulate the dynamic nature of the ECM, many reversible
      chemistries have been incorporated into hydrogels to regulate cell spreading,
      biochemical ligand presentation and matrix mechanics. For example, emerging
      trends include the use of molecular photoswitches or biomolecule hybridization to
      control polymer chain conformation, thereby enabling the modulation of the
      hydrogel between two states on demand. In addition, many non-covalent, dynamic
      chemical bonds have found increasing use as hydrogel crosslinkers or tethers for
      cell signalling molecules. These reversible chemistries will provide greater
      temporal control of adhered cell behaviour, and they allow for more advanced in
      vitro models and tissue-engineering scaffolds to direct cell fate.

PMID- 29214060
TI  - Interstitial lung disease: the diagnostic role of bronchoscopy.
AB  - Interstitial lung diseases (ILDs) form one of the most fascinating fields in
      pulmonary medicine. They also pose one of the greatest challenges for accurate
      diagnosis and proper treatment. Even within the recommended and warranted
      multidisciplinary approach, differentiating between one disease and another may
      lead to frustration, especially when proper lung tissue is not available for
      adequate pathological review. A surgical lung biopsy (SLB) might render enough
      tissue for histopathology, but this could come at the expense of high morbidity
      and even mortality, as in the case of usual interstitial pneumonia (UIP). Could
      bronchoscopy and its various techniques offer a safer and higher yield
      alternative? Since the very late 19th century, efforts have been made to better
      examine the airways, obtain tissue and treat various conditions. This resulted in
      the successive emergence of bronchoalveolar lavage (BAL), endobronchial and
      transbronchial forceps biopsies, until recently when transbronchial cryobiopsy
      surfaced as a nascent technique with much promise. The use of endobronchial
      ultrasound revolutionized the diagnosis and staging of lung cancer, while adding
      to the yield of other conditions such as sarcoidosis. Ongoing research, efforts
      and studies have continuously scrutinized the roles of various techniques in the
      approach to ILDs. For example, BAL seems to serve mostly to eliminate infection
      as an etiology or a complicating factor in the acute worsening of a fibrotic lung
      disease, while a predominant cellular component might be diagnostic, such as
      eosinophilia in eosinophilic lung disease, or lymphocytosis in hypersensitivity
      pneumonitis (HP). On the other hand, endobronchial biopsy's (EBB) role appears
      limited to sarcoidosis. As for transbronchial biopsy by forceps, the small sample
      size and related artifact appear to be limiting factors in making an accurate
      diagnosis. Recently, however, the use of cryotherapy via employing a cryoprobe in
      obtaining transbronchial lung biopsies is unfolding into a refined interventional
      method which might transform indefinitely our approach to the pathological
      diagnosis of the various ILDs.

PMID- 29214061
TI  - Medical thoracoscopy and its evolving role in the diagnosis and treatment of
      pleural disease.
AB  - Establishing the etiology of exudative pleural effusions in the setting of an
      unrevealing pleural fluid analysis often requires biopsies from the parietal
      pleura. While closed pleural biopsy (CPB) has been a popular minimally-invasive
      approach, it has a poor diagnostic yield, barring a diagnosis of tuberculous
      pleurisy. Medical thoracoscopy (MT) is a minimally-invasive ambulatory procedure
      performed under local anesthesia or moderate sedation which allows for direct
      visualization of biopsy targets as well as simultaneous therapeutic
      interventions, including chemical pleurodesis and indwelling tunneled pleural
      catheter (ITPC) placement. The excellent yield and favorable safety profile of MT
      has led to it replacing CPB for many indications, particularly in the management
      of suspected malignant pleural effusions. As experience with MT amongst
      interventional pulmonologists has grown, there is an increased appreciation for
      its important role alongside percutaneous and surgical approaches in the
      diagnosis and treatment of pleural disease.

PMID- 29214062
TI  - Management of oral antiplatelet agents and anticoagulation therapy before
      bronchoscopy.
AB  - Although, bronchoscopy is a relatively safe procedure, small amount of bleeding
      in the airway can have serious consequences. Careful consideration of the risks
      of diagnostic and therapeutic bronchoscopic intervention can help minimize
      potential complications. With increasing number of patients using antiplatelet
      and anticoagulation therapies, strategies for minimizing thromboembolic and
      operative bleeding events need to be included in the risk and benefit analyses.
      Growing evidence suggests that aspirin is safe and does not increase bleeding
      during bronchoscopy. In addition, despite small studies reporting that it may be
      safe to perform bronchoscopic procedures that have low risk for bleeding such as
      endobronchial ultrasound with transbronchial needle aspiration on clopidogrel, it
      is still recommended to hold it for 7 days prior to performing elective
      bronchoscopy. It is recommended to hold vitamin K antagonist, as well as new oral
      anticoagulation agents prior to bronchoscopy. The timing for pre-procedural
      discontinuation of anticoagulation therapy and the decision to bridge depend on
      the agent used, the renal function and the thromboembolic risk. In this review
      article, we will discuss available data regarding management of anticoagulation
      and antiplatelet therapy as it applies to bronchoscopic procedures.

PMID- 29214063
TI  - Bronchoscopic management of prolonged air leak.
AB  - Bronchopleural fistula (BPF) with prolonged air leak (PAL) is most often, though
      not always, a sequela of lung resection. When this complication occurs post
      operatively, it is associated with substantial morbidity and mortality. Surgical
      closure of the defect is considered the definitive approach to controlling the
      source of the leak, but many patients with this condition are suboptimal
      operative candidates. Therefore there has been active interest for decades in the
      development of effective endoscopic management options. Successful use of
      numerous bronchoscopic techniques has been reported in the literature largely in
      the form of retrospective series and, at best, small prospective trials. In
      general, these modalities fall into one of two broad categories: implantation of
      a device or administration of a chemical agent. Closure rates are high in
      published reports, but the studies are limited by their small size and multiple
      sources of bias. The endoscopic procedure currently undergoing the most
      systematic investigation is the placement of endobronchial valves. The aim of
      this review is to present a concise discussion on the subject of PAL and
      summarize the described bronchoscopic approaches to its management.

PMID- 29214064
TI  - Bronchoscopy for the diagnosis of peripheral lung lesions.
AB  - Peripheral pulmonary lesions (PPLs) are generally considered as lesions in the
      peripheral one-third of the lung although a precise definition and radiographic
      anatomical landmarks separating central and peripheral lesion does not yet exist.
      The radiographic detection of such lesions has increased significantly with the
      adoption of lung cancer screening programs. These lesions are not directly
      visible by regular flexible bronchoscopes as they are usually distal to the lobar
      and segmental bronchi. Traditionally, depending on location and clinical stage at
      presentation, these lesions were typically sampled by computerized tomography
      (CT) guided needle or surgical biopsy although some centers also used ultrasound
      and fluoroscopy guided percutaneous needle biopsy. Due to lack of direct
      visualization, the yield for bronchoscopic guided sampling especially of the
      small <2 cm pulmonary nodules was very low. Therefore, sampling has been
      preferentially performed by percutaneous CT guidance, which had high yield of
      above 90% but it comes at the cost of higher risk complications like pneumothorax
      with reported rate of 15% to 28%. Directly proceeding to surgical resection is
      also considered in appropriate candidates with high suspicion of malignancy
      without any evidence of distant metastasis but the proportion of such cases of
      lung cancer is low. The manuscript discussed the various bronchoscopic diagnostic
      modalities for peripheral pulmonary lesions. It is important to note that most of
      the studies in this field are relatively small, not randomized, suffer from
      selection bias, have considerable heterogeneity in sampling
      methodology/instruments and usually have been performed in high volume
      institutions by dedicated highly experienced proceduralists. The prevalence of
      malignancy in most of the reported cohorts has also been high which may result in
      higher diagnostic yields. All these factors need to be kept in mind before
      generalizing the results to individual centers and practices.

PMID- 29214065
TI  - Management of cardiac implantable electronic devices during interventional
      pulmonology procedures.
AB  - An increasing number of patients are receiving cardiac implantable electronic
      devices (CIED) now. Many of them need pulmonary procedures for various
      indications including, but not limited to, lung cancer and benign endobronchial
      lesions. Over the last two decades, interventional pulmonology (IP) has expanded
      its scope to include various modalities that use heat and electrical energy and
      in the process, create electromagnetic field in the vicinity. This raises
      concerns for electromagnetic interference (EMI) causing abnormal behavior in the
      CIEDs. While guidelines and recommendations on the peri-procedural management of
      CIEDs do exist, none of them directly address the pulmonary procedures. In this
      paper, we strive to review the available literature pertaining to the management
      of CIEDs in the context of EMI caused by the various IP procedures.

PMID- 29214066
TI  - A systematic approach to the management of massive hemoptysis.
AB  - Massive hemoptysis is regarded as a potentially lethal condition that requires
      immediate attention, and prompt action. Although minor hemoptysis is frequently
      encountered by most clinicians, massive hemoptysis in far less frequent and most
      physicians are not prepared to manage this time-sensitive clinical presentation
      in a systematic and timely fashion. Critical initial steps in management need to
      be implemented in an expedited fashion, such that patients may have a chance at a
      more definitive treatment. In this article, we review the definition, vascular
      anatomy, etiology, diagnostic evaluation, epidemiology and prognostic markers of
      massive hemoptysis. A systematic approach to management, stabilization and
      treatment options is followed. An algorithm is proposed for the management of
      massive hemoptysis and the importance of a multidisciplinary approach is
      emphasized.

PMID- 29214067
TI  - Malignant central airway obstruction.
AB  - This review comprehensively describes recent advances in the management of
      malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and
      devastating manifestation of primary lung cancer or metastatic disease. A variety
      of diagnostic modalities are available to provide valuable information to plan a
      therapeutic intervention. Clinical heterogeneity in the presentation of malignant
      CAO provides opportunities to adapt and utilize endoscopic technology and tools
      in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents
      are methods and instruments used to rapidly restore airway patency. Delayed
      bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can
      also be utilized in specific non-emergent situations to establish airway patency.
      Although data regarding the success and complications of therapeutic
      interventions are retrospective and characterized by clinical and outcome measure
      variability, the symptoms of malignant CAO can often be successfully palliated.
      Assessment of risks and benefits of interventions in each individual patient
      during the decision-making process forms the critical foundation of the
      management of malignant CAO.

PMID- 29214069
TI  - Anatomical considerations in bronchoscopy.
AB  - A thorough understanding of intrathoracic anatomy enables the interventional
      bronchoscopist to perform procedures efficaciously. The review of the anatomy of
      the thoracic cavity focuses first on the trachea and the relationship of the
      airway with surrounding structures, knowledge important for the safe conduct of
      bronchoscopic procedures. We then describe the anatomy of the pleural cavity
      relevant to the practitioner performing pleuroscopy.

PMID- 29214068
TI  - Diagnosis and management of malignant pleural effusions: state of the art in
      2017.
AB  - Malignant pleural effusion (MPE) is a known complication of both thoracic and
      extra thoracic malignancies. The presence of MPE regardless of the primary site
      translates into advanced stage disease. Diagnosis and management of MPE with the
      goals of palliation and improving quality of life poses a challenge for chest
      physicians. Recently, multiple studies have made attempts to answer questions
      regarding optimal management in various clinical scenarios. We will review the
      current evidence and available options for the management of MPE.

PMID- 29214070
TI  - Percutaneous tracheostomy: a comprehensive review.
AB  - Tracheostomy is a common procedure. It can be done surgically or percutaneously
      by dilating the stoma using Seldinger technique. Percutaneous tracheostomy (PT)
      is now routinely performed by surgeons and non-surgeons such as intensivists and
      anesthesiologists in the intensive care units (ICU) all over the world. Although
      obesity, emergent tracheostomy, coagulopathy, inability to extend the neck and
      high ventilator demand (HVD) were initially thought to be a relative
      contraindication, recent data suggest safety of PT in these patient population.
      Ultrasound can be helpful in limited cases to identify the neck structure
      especially in patients with a difficult anatomy. Bronchoscopy during PT can
      shorten the duration and avoid complications. PT has favorable complication rate,
      lower infection rate, shorter procedural duration and is cost-effective.
      Experience with the technique and careful planning is needed to minimize any
      avoidable potential complication.

PMID- 29214072
TI  - Asymptomatic malignant pleural effusion: to observe or to manage.

PMID- 29214071
TI  - Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in
      cystic fibrosis and its clinical use.
AB  - Cystic fibrosis (CF) is a progressive life threatening multisystem genetic
      disease which affects the CF transmembrane conductance regulator channel.
      Respiratory causes remain the most common mortality in CF. With the onset of
      newborn screening, initiating treatments both for prophylaxis and disease
      management, optimizing nutritional support, and developing therapies targeting CF
      transmembrane conductance regulator protein, this has significantly changed the
      face of managing this devastating disease. Bronchoscopy and related procedures
      such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected
      brush sampling have been looked at in the management of CF as patients with CF
      continue to live longer with the help of newer therapies, the microbiome in the
      lung becomes less diverse along with increased occurrences for noninfectious
      causes of airway diseases. Though bronchoscopy has been used in conjunction with
      other modalities such as computed tomography and sputum induction providing a
      better understanding of the progression of the disease, it still remains valuable
      in the diagnosis and management of CF.

PMID- 29214074
TI  - Tilt, Decentration, and Internal Higher-Order Aberrations of Sutured Posterior
      Chamber Intraocular Lenses in Patients with Open Globe Injuries.
AB  - Purpose: To evaluate the tilt, decentration, and internal higher-order
      aberrations (HOAs) of sutured posterior-chamber intraocular lenses (IOLs) in
      patients with open globe injuries. Methods: 46 consecutive patients (47 eyes) who
      underwent transsclerally sutured IOL implantation were enrolled in this
      prospective cohort study. Nineteen eyes had a history of open globe injury. The
      tilt and decentration of the IOLs and the visual quality were measured 1 month
      after surgery. Results: The horizontal tilt and decentration of the IOLs in the
      open-globe-injury group were significantly higher than those in the control group
      (both P < 0.05). In the open-globe-injury group, the horizontal decentration was
      significantly greater in the limbus-sclera-involved group (n = 11) than in the
      only-cornea-involved group (n = 8, P = 0.040). The internal coma, 3rd-order, and
      total HOA values at pupil sizes of 4 mm (P = 0.006) and 6 mm (P = 0.013) were
      significantly higher in the open-globe-injury group than in the controls.
      Consequently, the optical quality data for the modulation transfer function and
      the Strehl ratio (all P < 0.05) were significantly poorer in the open-globe
      injury group. Conclusions: Open globe injuries damage the structural integrity of
      the eyeball, resulting in more-misaligned sutured IOLs and poorer visual quality.

PMID- 29214075
TI  - Air Bubble Technique for Fundus Visualization during Vitrectomy in Aphakia.
AB  - Purpose: To evaluate the efficacy and safety of air bubble technique for
      vitrectomy in aphakia. Study Design: Prospective interventional uncontrolled case
      series. Methods: This study included 53 eyes of 53 patients who are phakic and
      indicated for phacovitrectomy (7 eyes, group 1), aphakic and indicated for
      vitrectomy (22 eyes, group 2), or underwent unplanned vitrectomy for immediate
      management of a phacoemulsification surgery complicated by rupture posterior
      capsule with dropped nucleus, fragments, or IOL (24 eyes, group 3). Cases with
      complicated vitreoretinal pathology were not included in this study. All
      vitrectomy surgeries were conducted by the air bubble technique in the anterior
      chamber. Main outcomes included anatomical success, visual acuity, and
      intraoperative and postoperative complications. Results: The surgical success was
      achieved in 50 eyes (94.3%). Conversion to BIOM viewing system was needed in the
      retinal detachment cases of groups 1 and 2. The mean overall LogMAR visual acuity
      was significantly improved from 1.29 +/- 0.58 preoperatively to 0.56 +/- 0.19 at
      the final visit, 6 months postoperatively (P < 0.001). Conclusion: The air bubble
      technique as visualization method for vitrectomy in aphakia is an effective and
      cheap technique for immediate management of complications of phacoemulsification
      surgery. This trial is registered with Pan African Clinical Trial Registry
      PACTR201709002466296.

PMID- 29214076
TI  - Posterior Segment Ocular Trauma: Timing and Indications for Vitrectomy.

PMID- 29214073
TI  - Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and
      Human Model Systems.
AB  - Ocriplasmin (Jetrea(r)) is a recombinant protease used to treat vitreomacular
      traction. To gain insight into vitreoretinal observations reported after
      ocriplasmin treatment, we have developed an in vivo porcine ocriplasmin-induced
      posterior vitreous detachment (PVD) model in which we investigated vitreoretinal
      tissues by optical coherence tomography, histology, and cytokine profiling. Eight
      weeks postinjection, ocriplasmin yielded PVD in 82% of eyes. Subretinal fluid
      (85%) and vitreous hyperreflective spots (45%) were resolved by week 3.
      Histological analysis of extracellular matrix (ECM) proteins such as laminin,
      fibronectin, and collagen IV indicated no retinal ocriplasmin-induced ECM
      distribution changes. Retinal morphology was unaffected in all eyes. Cytokine
      profiles of ocriplasmin-treated eyes were not different from vehicle. In cell
      based electrical resistance assays, blood-retinal barrier permeability was
      altered by ocriplasmin concentrations of 6 MUg/mL and higher, with all effects
      being nontoxic, cell-type specific, and reversible. Ocriplasmin was actively
      taken up by RPE and Muller cells, and our data suggest both lysosomal and
      transcellular clearance routes for ocriplasmin. In conclusion, transient
      hyperreflective spots and fluid in a porcine ocriplasmin-induced PVD model did
      not correlate with retinal ECM rearrangement nor inflammation. Reversible in
      vitro effects on blood-retinal barrier permeability provide grounds for a
      hypothesis on the mechanisms behind transient subretinal fluid observed in
      ocriplasmin-treated patients.

PMID- 29214077
TI  - Mortality and Its Predictors among HIV Infected Patients Taking Antiretroviral
      Treatment in Ethiopia: A Systematic Review.
AB  - Background: Even though the benefit of antiretroviral therapy (ART) is well
      established, there is a regional variation in the extent of its benefit. The aim
      of this review is to highlight mortality and its predictors in Ethiopian adult
      HIV patients who were on ART. Methods: Relevant articles were searched on PubMed
      and Google Scholar databases. The search terms used in different combinations
      were predictor/determinant/factors, mortality/death/survival, HIV, ART/HAART, and
      Ethiopia. Result: 5-40.8% of the patients died during the follow-up period. More
      than half (50-68.8%) of the deaths occurred within 6 months of initiating ART.
      Advanced stage disease (stage III and stage IV), nonworking functional status
      (bedridden and ambulatory), low baseline CD4 count, low baseline hemoglobin
      level, TB coinfection, lower baseline weight, and poor treatment adherence were
      commonly identified as predictors of death in HIV patients. Conclusion: 5-40.8%
      of HIV patients in Ethiopia die in 2-5 years of initiating antiretroviral
      treatment. Most of the deaths in HIV patients occur early in the course of
      treatment. Special emphasis should be given for patients with advanced stage
      disease, nonworking functional status, low baseline CD4 count, low baseline
      hemoglobin level, TB coinfection, lower baseline weight, and poor treatment
      adherence.

PMID- 29214078
TI  - The Profile of Saudi Nursing Workforce: A Cross-Sectional Study.
AB  - Introduction: The Royal Monarchy in Saudi Arabia decreed that all sectors of the
      workforce would be subject to a policy of "Saudisation" to reduce the reliance on
      the expatriate workforce and to reduce the unemployment rate of Saudi nationals
      (Al-Mahmoud et al., 2012). Methodology: A cross-sectional design was chosen to
      investigate the research questions. The population of this study comprised Saudi
      Registered Nurses working in MOH hospitals in Riyadh which is the main health
      care provider in Saudi Arabia (Aboul-Enein, 2002; MOH, 2009). Results and
      Findings: A total number of 1,198 questionnaires were distributed and 61.2% (n =
      741) were returned. The findings of the study showed that the questionnaires were
      collected from an equal portion of the study locale and that a sample of 741 is
      enough to create a strong conclusion and answer the problem set in this study and
      all the questions in the study have been provided with answers with enough data
      and literatures to supports its findings. Conclusion and Recommendations: The
      results indicate that an increase in the recruitment of Saudi males may simply
      reflect cultural issues such as gender specific facilities and the Saudisation
      program's nondiscriminatory approach to employment of both genders into nursing.

PMID- 29214079
TI  - miR-19a and miR-20a and Tissue Factor Expression in Activated Human Peripheral
      Blood Mononuclear Cells.
AB  - Background and Aims: To investigate the behaviour of miR-19a and miR-20a, two
      microRNAs involved in posttranscriptional modulation of TF expression in
      peripheral blood mononuclear cells (PBMCs) exposed to high glucose (HG) and
      lipopolysaccharide (LPS), and to evaluate the involvement of angiotensin II in
      that process. Methods: TF Procoagulant Activity (PCA, one-stage clotting assay),
      antigen (Ag, ELISA), and miR-19a and miR-20a levels (specific TaqMan(r) MicroRNA
      Assays) were evaluated in PBMCs exposed to high glucose (HG, 50 mM), LPS (100
      ng/mL), and Olmesartan (OLM, 10-6 M), an angiotensin II type 1 receptor
      antagonist. Results: HG increased TF expression and decreased both miRs as
      compared to control glucose conditions (11.1 mM). In HG-activated PBMCs, LPS
      stimulated TF expression and downregulated miR-20a, an effect reverted by OLM (10
      6 M); miR-19a expression was unchanged by LPS in both CG and HG conditions.
      Conclusions: miR-19a and miR-20a are inhibited by inflammatory stimuli active on
      TF expression and their response differs by the stimulus under investigation;
      angiotensin II may participate in that mechanism.

PMID- 29214081
TI  - A Rare Complication of a TAP Block Performed after Caesarean Delivery.
AB  - The transversus abdominis plane block is a regional anesthesia technique that has
      become popular. Being a relatively simple procedure, the TAP block has an
      excellent safety profile and major complications are rare. We present a case of
      transient femoral nerve palsy occurring after a TAP block with involvement of the
      sacral plexus for a patient who had undergone a caesarean section.

PMID- 29214080
TI  - HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator.
AB  - Although many studies have investigated the functions of histidine triad
      nucleotide-binding protein 1 (HINT1), its roles in neurobiological processes
      remain to be fully elucidated. As a member of the histidine triad (HIT) enzyme
      superfamily, HINT1 is distributed in almost every organ and has both enzymatic
      and nonenzymatic activity. Accumulating clinical and preclinical evidence
      suggests that HINT1 may play an important role as a neuroplastic mediator in
      neuropsychiatric diseases, such as schizophrenia, inherited peripheral
      neuropathies, mood disorders, and drug addiction. Though our knowledge of HINT1
      is limited, it is believed that further research on the neuropathological
      functions of HINT1 would eventually benefit patients with neuropsychiatric and
      even psychosomatic diseases.

PMID- 29214082
TI  - Congenital Absence of Left Circumflex Artery: A Case Report and Review of the
      Literature.
AB  - Congenital absence of the left circumflex artery is a rare coronary anomaly with
      few reported cases in the literature. These patients are usually diagnosed
      incidentally when they undergo coronary angiography or coronary CT to rule out
      underlying coronary artery disease. In this article, we report a case of a 46
      year-old man who was incidentally found to have a congenitally absent left
      circumflex artery with a superdominant right coronary artery after a workup was
      initiated for frequent premature ventricular contractions and regional wall
      motion on echocardiogram. A review of the clinical presentation, symptoms, and
      diagnostic modalities used to diagnose this entity is presented.

PMID- 29214083
TI  - Adenomatoid Odontogenic Tumor Associated with an Impacted Maxillary Lateral
      Incisor: A Case Report with Five-Year Follow-Up.
AB  - Adenomatoid odontogenic tumor (AOT), a benign (hamartomatous) lesion of
      odontogenic origin, is an uncommon tumor which affects mainly females in the
      second decade. This lesion is most commonly associated with an impacted maxillary
      canine. This paper reported a case of AOT, in a 16-year-old female, associated
      with an impacted maxillary left lateral incisor. The evolution of this tumor was
      followed over 36 months and 24 months after excision.

PMID- 29214084
TI  - Coexistence of Primary Hyperaldosteronism and Graves' Disease, a Rare Combination
      of Endocrine Disorders: Is It beyond a Coincidence-A Case Report and Review of
      the Literature.
AB  - Background: Primary hyperaldosteronism is a known cause for secondary
      hypertension. In addition to its effect on blood pressure, aldosterone exhibits
      proinflammatory actions and plays a role in immunomodulation/development of
      autoimmunity. Recent researches also suggest significant thyroid dysfunction
      among patients with hyperaldosteronism, but exact causal relationship is not
      established. Autoimmune hyperthyroidism (Graves' disease) and primary
      hyperaldosteronism rarely coexist but underlying mechanisms associating the two
      are still unclear. Case Presentation: A 32-year-old Sri Lankan female was
      evaluated for new onset hypertension in association with hypokalemia. She also
      had features of hyperthyroidism together with high TSH receptor antibodies
      suggestive of Graves' disease. On evaluation of persistent hypokalemia and
      hypertension, primary hyperaldosteronism due to right-sided adrenal adenoma was
      diagnosed. She was rendered euthyroid with antithyroid drugs followed by right
      sided adrenalectomy. Antithyroid drugs were continued up to 12 months, after
      which the patient entered remission of Graves' disease. Conclusion: Autoimmune
      hyperthyroidism and primary hyperaldosteronism rarely coexist and this case
      report adds to the limited number of cases documented in the literature.
      Underlying mechanism associating the two is still unclear but possibilities of
      autoimmune mechanisms and autoantibodies warrant further evaluation and research.

PMID- 29214085
TI  - SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and
      Behavioral Abnormalities.
AB  - SOX5 encodes a conserved transcription factor implicated in cell-fate decisions
      of the neural lineage. SOX5 haploinsufficiency induced by larger genomic
      deletions has been linked to a recognizable pediatric syndrome combining
      developmental delay with intellectual disability, mild dysmorphism, inadequate
      behavior, and variable additional features including motor disturbances. In
      contrast to SOX5-involving deletions, examples of pathogenic SOX5 small coding
      variations are sparse in the literature and have been described only in singular
      cases with phenotypic abnormalities akin to those seen in the SOX5 microdeletion
      syndrome. Here a novel SOX5 loss-of-function point mutation, c.13C>T (p.Arg5X),
      is reported, identified in the course of exome sequencing applied to the
      diagnosis of an unexplained adult-onset motor disorder. Aged 43 years, our female
      index patient demonstrated abrupt onset of mixed generalized hyperkinesia, with
      dystonic and choreiform movements being the most salient features. The movement
      disorder was accompanied by behavioral problems such as anxiety and mood
      instability. The mutation was found to be inherited to the patient's son who
      manifested abnormal behavior including diminished social functioning, paranoid
      ideation, and anxiety since adolescence. Our results expand the compendium of
      SOX5 damaging single-nucleotide variation mutations and suggest that SOX5
      haploinsufficiency might not be restrictively associated with childhood-onset
      syndromic disease.

PMID- 29214087
TI  - Invasive Nontyphoidal Salmonella Infection in a Patient with Early-Stage Chronic
      Lymphocytic Leukemia.
AB  - We describe a case of a 72-year-old man with early-stage chronic lymphocytic
      leukemia (CLL) who presented with invasive nontyphoidal Salmonella (iNTS)
      infection, necrotizing pneumonia, and chronic infection of a hilar lymph node.
      Infection is a major cause of death in patients with CLL. Though few cases of
      iNTS infection associated with CLL have been described in the literature, to our
      knowledge this is the first reported case of iNTS-associated necrotizing
      pneumonia. Immunocompromised state in patients, even with early-stage CLL, likely
      predisposes them to invasive infection with intracellular organisms, such as
      Salmonella spp. In this case, successful treatment was achieved with prolonged
      course of intravenous followed by oral antibiotics without any surgical removal
      of infected focus.

PMID- 29214086
TI  - Erdheim-Chester Disease with No Skeletal Bone Involvement and Massive Weight
      Loss.
AB  - Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell
      histiocytosis, with only 550 cases reported worldwide. ECD is characterized by
      diffuse histiocytic infiltration of multiorgans. The age of presentation of this
      disease is typically between 40 and 70 years. Bone disease is the most common
      symptom, as unique radiological findings of long bone sclerosis occur in 96% of
      cases. Furthermore, BRAF V600E mutation is detected in 60% of ECD cases. In this
      manuscript, we are describing a unique case of ECD; the patient is younger than
      most reported cases and has no bone pain or any skeletal involvement. This
      patient has unintentionally lost about 50% of his body mass and is suffering from
      progressive cerebellar manifestations with radiological evidence of cerebellar
      atrophy, in contrast to the usual ECD manifestation of cerebellar infiltration.
      In addition, the patient has cardiac, retroperitoneal, and perinephric
      involvement, but he retains his sexual drive and fertility. A tissue biopsy from
      the retroperitoneal mass displayed typical morphological and immunohistochemical
      features of ECD, and BRAF V600E mutation was detected. He was treated with
      pegylated interferon alpha, but his disease progressed and the treatment was
      changed to vemurafenib to which he had an excellent response at 6 weeks.

PMID- 29214088
TI  - Advanced Alveolar Soft Part Sarcoma Treated with Pazopanib over Three Years.
AB  - Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that generally occurs
      in adolescents and young adults. It progresses slowly, but lung and brain
      metastases often occur in the early phase of the clinical course, and
      chemotherapy has been reported as not being effective for ASPS. Pazopanib is a
      multitargeted tyrosine kinase inhibitor that has been clinically available from
      November 2012 in Japan. This is a case report of a patient presented with
      multiple lung metastases and unresectable primary abdominal ASPS. We initially
      treated this patient by systemic chemotherapy with combination use of ifosfamide
      and doxorubicin. Stable disease was observed without any objective response.
      Then, we finally started to administrate pazopanib 800 mg/day. After 25 months of
      pazopanib administration, slight tumor reduction and a decrease of enhancement
      were observed. Objective responses were achieved for both the primary tumor and
      metastatic lung tumor; however, a newly developed brain metastasis was
      subsequently identified. Based on this case, pazopanib appears effective against
      ASPS, except for brain metastases. This case suggests that pazopanib may be
      useful as a first-line drug against unresectable ASPS and that longitudinal
      assessment of brain metastasis should be performed in similar cases.

PMID- 29214089
TI  - Systemic Treatment of Metastatic Conjunctival Melanoma.
AB  - Conjunctival melanoma (CM) is an exceptionally rare tumor, with a propensity for
      local and distant recurrence, with the lungs, skin, liver, and brain being the
      most common sites of metastasis. Recent progress in systemic treatments, with
      checkpoint inhibitors and targeted therapies blocking BRAF and MEK, has redefined
      the standard of care of advanced unresectable and metastatic melanoma. Although
      most trials did not include patients with conjunctival melanoma, its close
      molecular and genetic relationship to cutaneous melanoma might suggest a similar
      response to these novel agents. The authors describe two uncommon cases of
      metastatic conjunctival melanomas with distinct genetic profiles and, as such,
      submitted to different systemic treatments.

PMID- 29214090
TI  - Bone Resection for Isolated Ulnar Head Fracture.
AB  - Distal ulnar fractures often occur with distal radius fractures (DRFs), and ulnar
      styloid fractures commonly occur in the setting of DRF. However, isolated ulnar
      head fractures are rare. We report a case of isolated ulnar head fracture in
      which we performed bone resection because the ulnar head bone fragment fractured
      when internal screw fixation was attempted. His outcome at 18 months
      postoperatively was considered excellent. However, we do not advocate bone
      resection other than failure of fixation and the difficult case to perform
      internal fixation. Longer follow-up would be needed because bone resection might
      lead to osteoarthritis of the distal radioulnar joint in the future.

PMID- 29214091
TI  - Keeping an Open Mind: Cognitive Bias in the Evaluation of an Infant with
      Posterior-Lateral Rib Fractures.
AB  - A four-month-old former premature male is incidentally found to have posterior
      lateral rib fractures during evaluation of a febrile illness. This finding led to
      the initiation of a workup for nonaccidental trauma. A thorough history and
      physical exam ultimately led to the diagnosis, which was not related to abuse.
      This case highlights a rare sequela of patent ductus arteriosus repair, cautions
      medical teams to remain aware of how cognitive bias can affect diagnostic
      decision-making, and emphasizes the importance of a thorough history, physical
      exam, and medical record review in cases of suspected nonaccidental trauma.

PMID- 29214092
TI  - Pyogenic Odontoid Osteomyelitis with Sinus Thrombosis.
AB  - 71/F presented with left sided headaches and neck pain with nuchal rigidity
      progressively worsening over 3 weeks with no other neurologic symptoms. Odontoid
      osteomyelitis with epidural abscess was discovered on further workup with
      neuroimaging. Concurrent jugular vein and transverse sinus venous thrombosis was
      also found and suspected to be secondary to the pyogenic odontoid osteomyelitis.
      Patient was treated with intravenous antibiotics for the osteomyelitis as well as
      intravenous heparin for the venous thrombosis. To our knowledge, this is the
      first case reported in literature of transverse sinus venous thrombosis secondary
      to odontoid osteomyelitis.

PMID- 29214093
TI  - Should Skin Biopsies Be Performed in Patients Suspected of Having Parkinson's
      Disease?
AB  - In patients with Parkinson's disease (PD), the molecularly misfolded form of
      alpha-synuclein was recently identified in cutaneous autonomic nerve fibers which
      displayed increased accumulation even in early disease stages. However, the
      underlying mechanisms of synucleinopathic nerve damage and its implication for
      brain pathology in later life remain to be elucidated. To date, specific
      diagnostic tools to evaluate small fiber pathology and to discriminate
      neurodegenerative proteinopathies are rare. Recently, research has indicated that
      deposition of alpha-synuclein in cutaneous nerve fibers quantified via
      immunohistochemistry in superficial skin biopsies might be a valid marker of PD
      which could facilitate early diagnosis and monitoring of disease progression.
      However, lack of standardization of techniques to quantify neural alpha-synuclein
      deposition limits their utility in clinical practice. Additional challenges
      include the identification of potential distinct morphological patterns of
      intraneural alpha-synuclein deposition among synucleinopathies to facilitate
      diagnostic discrimination and determining the degree to which structural damage
      relates to dysfunction of nerve fibers targeted by alpha-synuclein. Answering
      these questions might improve our understanding of the pathophysiological role of
      small fiber neuropathy in Parkinson's disease, help identify new treatment
      targets, and facilitate assessment of response to neuroprotective treatment.

PMID- 29214094
TI  - Study of a Two-Step Centrifugation Protocol for Concentrating Cells and Growth
      Factors in Bovine Platelet-Rich Plasma.
AB  - There is a lack of information about the methods used for bovine platelet-rich
      plasma (PRP)/platelet-rich gel (PRG) procurement, including information on
      platelet (PLT), white blood cell (WBC) in PRP, and growth factor release from PRG
      supernatants. The aims of this study were to compare and to correlate the PLT,
      WBC, transforming growth factor beta-1 (TGF-beta1), and platelet-derived growth
      factor BB (PDGF-BB) concentrations in bovine whole blood, plasma, and four PRP
      layers and their respective PRG supernatants: A and B (obtained by a single
      centrifugation tube method at 720g/5 min) and C and D (obtained by a double
      centrifugation tube method, by using two centrifugation episodes at 720g/5 min).
      PLT and WBC counts were significantly higher in PRP-C, followed by whole blood,
      PRP-A, PRP-B, and PRP-D. TGF-beta1 concentrations were significantly higher in
      PRG-B supernatants and its correspondent PRP-B lysate when compared to the other
      PRG supernatants and plasma. Supernatants from PRG-A, PRG-B, and PRG-D had
      equivalent TGF-beta1 concentrations. PDGF-BB concentrations were not
      statistically different between the hemoderivatives. Significant Pearson
      correlations were noted between PLT counts and WBC counts (0.8) and between PLT
      counts and PLT distribution width (0.6). Further studies should be performed to
      assess the potential clinical applications of these PRPs.

PMID- 29214095
TI  - Separation and Determination of Fe(III) and Fe(II) in Natural and Waste Waters
      Using Silica Gel Sequentially Modified with Polyhexamethylene Guanidine and
      Tiron.
AB  - Silica gel, sequentially modified with polyhexamethylene guanidine and
      pyrocatechin-3,5-disulfonic acid (Tiron), was suggested for sorption separation
      and determination of Fe(III) and Fe(II). It was found that quantitative
      extraction of Fe(III) and its separation from Fe(II) were attained at pH 2.5-4.0,
      while quantitative extraction of Fe(II) was observed at pH 6.0-7.5. An intensive
      signal with g = 4.27, which is characteristic for Fe(III), appeared in EPR
      spectra of the sorbents after Fe(II) and Fe(III) sorption. During interaction
      between Fe(II) and Tiron, fixed on the sorbent surface, its oxidation up to
      Fe(III) occurred. Red-lilac complexes of the composition FeL3 were formed on the
      sorbent surface during sorption regardless of initial oxidation level of iron.
      Diffuse reflectance spectrum of surface complexes exhibited wide band with
      slightly expressed maxima at 480 and 510 nm. Procedures for separation and
      photometric determination of Fe(III) and Fe(II) at the joint presence and total
      Fe content determination as Fe(II) in waste and natural waters was developed. The
      limit of detection for iron was 0.05 MUg per 0.100 g of the sorbent. The
      calibration graph was linear up to 20.0 MUg of Fe per 0.100 g of the sorbent. The
      RSD in the determination of more than 0.2 MUg of Fe was less than 0.06.

PMID- 29214096
TI  - Childbearing intentions among sexually active HIV-infected and HIV-uninfected
      female adolescents in South Africa.
AB  - Women of reproductive age account for nearly half of all HIV-infected people
      worldwide. Childbearing intention among HIV-infected women is complicated by
      social and reproductive concerns related to their HIV status. We conducted a
      cross-sectional study of HIV-infected and HIV-uninfected sexually active South
      African women aged 17 to 21 in order to compare their childbearing intentions and
      to identify predictors of the desire to have children among women with HIV. We
      found the rate of childbearing intention to be similarly high among both HIV
      infected and HIV-uninfected study participants (80 and 79% respectively, p=0.81).
      History of previous parity was found to be associated with decreased intention to
      have children. No difference in childbearing intention was found between HIV
      infected women on anti-retroviral therapy (ART) and women not on ART. High rates
      of childbearing intention among HIV-infected women require integration of
      reproductive health services with comprehensive HIV/AIDS care in order to
      mitigate the risks of sexual and vertical transmission of HIV.

PMID- 29214097
TI  - Needle-Tissue Interaction Force State Estimation for Robotic Surgical Suturing.
AB  - Robotically Assisted Minimally Invasive Surgery (RAMIS) offers many advantages
      over manual surgical techniques. Most of the limitations of RAMIS stem from its
      non-intuitive user interface and costs. One way to mitigate some of the
      limitations is to automate surgical subtasks (e.g. suturing) such that they are
      performed faster while allowing the surgeon to plan the next step of the
      procedure. One component of successful suture automation is minimizing the
      internal tissue deformation forces generated by driving a needle through tissue.
      Minimizing the internal tissue forces requires segmenting the tissue deformation
      forces from other components of the needle tissue interaction (e.g. friction
      force). This paper proposes an Unscented Kalman Filter which can successfully
      model the force components, in particular the internal deformation force,
      generated by a needle as it is driven through a sample of tissue.

PMID- 29214098
TI  - Safety and Quality Concerns Regarding Over-the-Counter Sexual Enhancement
      Products Sold in the USA Market Pose a Major Health Risk.
AB  - Safety and quality concerns regarding over the counter sexual enhancement
      products sold in the USA market pose a major health risk to the general public.
      Nevertheless, the use of herbal medicines continues to expand rapidly across
      world and many people perceive usage of herbal medication as a safe and reliable
      way to improve health outcome. The safety of herbal supplements has become a
      globally major concern in national and international health authorities due to
      increasing adverse events and adulterations associated with usage of herbal
      medications. These non FDA approved products with unknown ingredients are widely
      accessible for purchase ranging from local food, drug stores and to the internet.
      These Erectile Dysfunction (ED) pills may contain Sildenafil, the active
      ingredient of Viagra in much higher quantity then legally prescribed by a
      licensed physician or they may contain unknown quantities of Thiosildenafil, the
      active ingredient in Cialis. The types of chemicals found in these medications
      are making it harder for regulatory authorities to track them down. These
      products keep the consumer in the dark in terms of the quantity, ingredients,
      effectiveness and possible side effects. These sexual enhancement products are
      being sold as safe and natural with false hopes to resolve erectile dysfunction.
      Patients who are prone to impulsive hypersexual behavior such as patients with
      bipolar disorder, substance use, borderline personality disorder and those who
      may feel adamant to discuss erectile dysfunction with their physicians are more
      likely to become the victims of using illicit medications/ drugs with serious
      health risks consequences. We present a case report of an individual with bipolar
      disorder and hypersexual behavior who became victim to over the counter sexual
      enhancement products/supplements which caused serious health and life threatening
      consequences.

PMID- 29214099
TI  - Geospatial Associations Between Tobacco Retail Outlets and Current Use of
      Cigarettes and e-Cigarettes among Youths in Texas.
AB  - Introduction: To identify the geospatial association between the presence of
      tobacco retail outlets (TRO) around schools' neighborhoods, and current use of
      cigarettes and e-cigarettes among adolescents in four counties in Texas. Methods:
      Students in grades 6, 8 and 10th were surveyed in their schools in 2014-2015. The
      schools' addresses was geocoded to determine the presence of at least one TRO
      within half a mile of the school. Two outcomes were considered: past 30-day use
      of (a) cigarettes and (b) e-cigarettes. Bayesian structured additive regression
      models and Kriging methods were used to estimate the geospatial associations
      between the presence of TRO and use in three counties: Dallas/Tarrant, Harris,
      and Travis. Results: We observed a geospatial association between the presence of
      TRO around the schools and current use of cigarettes in the eastern area of
      Dallas County and in the southeastern area of Harris County. Also, a geospatial
      association between the presence of TRO around the schools and current use of e
      cigarettes was observed in the entire Tarrant County and in the northeastern area
      of Harris County. Conclusions: There were geospatial associations between the
      presence of TRO around some schools and cigarette/e-cigarette use among students,
      but this association was not consistent across all the counties. More research is
      needed to determine why some areas are at higher risk for this association.

PMID- 29214100
TI  - A new direction for Dermatology Practical & Conceptual.

PMID- 29214102
TI  - White rosettes in discoid lupus erythematosus: a new dermoscopic observation.
AB  - White rosettes are shiny white structures seen as four oval-shaped points that
      come together in the center. They resemble four-leaf clover [1]. Earlier it was
      thought they were specific for actinic keratosis and squamous cell carcinoma, but
      they are noted in many other conditions [2]. With polarized light dermoscopy, it
      is evident that rosettes are seen only and they are due to the optical effect
      between polarized light and follicular structures [3]. Here, authors describe
      cases of discoid lupus erythematosus (DLE) demonstrating rosettes under polarized
      dermoscopy.

PMID- 29214101
TI  - Cell junction protein armadillo repeat gene deleted in velo-cardio-facial
      syndrome is expressed in the skin and colocalizes with autoantibodies of patients
      affected by a new variant of endemic pemphigus foliaceus in Colombia.
AB  - Background: We previously described a new variant of endemic pemphigus foliaceus
      in El Bagre, Colombia, South America (El Bagre-EPF, or pemphigus Abreu-Manu). El
      Bagre-EPF differs from other types of EPF clinically, epidemiologically,
      immunologically and in its target antigens. We reported the presence of patient
      autoantibodies colocalizing with armadillo repeat gene deleted in velo-cardio
      facial syndrome (ARVCF), a catenin cell junction protein colocalizing with El
      Bagre-EPF autoantibodies in the heart and within pilosebaceous units along their
      neurovascular supply routes. Here we investigate the presence of ARVCF in skin
      and its possibility as a cutaneous El Bagre-EPF antigen. Methods: We used a case
      control study, testing sera of 45 patients and 45 controls via direct and
      indirect immunofluorescence (DIF/IIF), confocal microscopy, immunoelectron
      microscopy and immunoblotting for the presence of ARVCF and its relationship with
      El Bagre-EPF autoantibodies in the skin. We also immunoadsorbed samples with
      desmoglein 1 (Dsg1) ectodomain (El Bagre-EPF antigen) by incubating with the
      positive ARVCF samples from DIF and IIF. Results: ARVCF was expressed in all the
      samples from the cases and controls. Immunoadsorption with Dsg1 on positive ARVCF
      immunofluorescence DIF/IIF cases showed that the immune response was present
      against non-desmoglein 1 antigen(s). Overall, 40/45 patients showed
      colocalization of their autoantibodies with ARVCF in the epidermis; no controls
      from the endemic area displayed colocalization. Conclusions: We demonstrate that
      ARVCF is expressed in many areas of human skin, and colocalizes with the majority
      of El Bagre-EPF autoantibodies as a putative antigen.

PMID- 29214103
TI  - In vivo intraoral reflectance confocal microscopy of an amalgam tattoo.
AB  - The majority of oral pigmentations are benign lesions such as nevi, melanotic
      macules, melanoacanthomas or amalgam tattoos. Conversely, mucosal melanomas are
      rare but often lethal; therefore, excluding oral melanomas in this setting is
      crucial. Reflectance confocal microscopy is a non-invasive, in vivo imaging
      system with cellular resolution that has been used to distinguish benign from
      malignant pigmented lesions in the skin, and more recently in the mucosa.
      However, lesions located posteriorly in the oral cavity are difficult to assess
      visually and difficult to biopsy due to their location. Herein we present a
      patient with previous multiple melanomas presenting with an oral amalgam tattoo
      in the buccal mucosa, which was imaged using an intraoral telescopic probe
      attached to a commercially available handheld RCM. In this case report we
      describe this novel probe, the first RCM description of an amalgam tattoo and we
      discuss its differences with the findings described in oral melanomas.

PMID- 29214105
TI  - Dermoscopy of chromoblastomycosis.
AB  - Chromoblastomycosis is a chronic cutaneous fungal infection commonly caused by
      Fonsacea and Cladophialophora spp. Dermoscopy is a non-invasive, real-time
      diagnostic tool for rapid bedside diagnosis of various inflammatory and non
      inflammatory disorders and can be an excellent modality for evaluation of
      cutaneous mycosis, for which it shows characteristic brown dots, crust, scales
      and yellow orange structures.

PMID- 29214104
TI  - A spermidine-based nutritional supplement prolongs the anagen phase of hair
      follicles in humans: a randomized, placebo-controlled, double-blind study.
AB  - Background: Spermidine has been shown both in vitro and in mice models to have an
      anagen-prolonging effect on hair follicles (HFs). Objectives: To evaluate the
      effects of a spermidine-based nutritional supplement on the anagen phase of HFs
      in healthy human subjects in a randomized, double-blind, placebo-controlled
      trial. Methods: One hundred healthy males and females were randomized to receive
      a tablet containing a spermidine-based nutritional supplement or a placebo once
      daily for 90 days. At the beginning and the end of the treatment period, 100 HFs
      were plucked and subjected to microscopic evaluation to determine the number of
      anagen V-VI HFs, and immunohistochemical examination was performed to quantify
      the Ki-67 and c-Kit levels in the hair bulbs. Pull test was performed after three
      and six months. Results: The spermidine-based nutritional supplement increased
      the number of anagen V-VI HFs after three months of treatment, accompanied by
      increased Ki-67, a marker for cellular proliferation, and decreased c-Kit, a
      marker for apoptosis, levels. All results were also significantly better when
      compared to the placebo group. The pull test remained negative after six months
      in all patients receiving the spermidine supplement, while 68% of the subjects in
      the placebo group had a positive pull test. Conclusions: This preliminary study
      shows that a spermidine-based nutritional supplement can prolong the anagen phase
      in humans, and therefore might be beneficial for hair loss conditions. Further
      studies are needed to evaluate its effects in specific different clinical
      settings.

PMID- 29214106
TI  - Basal serum cortisol and adrenocorticotropic hormone levels in patients with
      atopic dermatitis.
AB  - Background: Certain studies suggest that percutaneous absorption of topical
      steroids may cause suppression of hypothalamic-pituitary-adrenal axis (HPAA) in
      atopic dermatitis (AD) patients. This study aimed to investigate the basal serum
      cortisol, adrenocorticotropic hormone (ACTH), and IgE levels in patients with AD
      and their correlation with the disease severity. Methods: Levels of basal serum
      cortisol, ACTH, and IgE were assessed by ELISA in 31 patients with AD and 31
      controls. Clinical severity of AD was evaluated by the scoring of atopic
      dermatitis (SCORAD) index. Results: No statistical difference was observed
      between the two groups for basal serum cortisol and ACTH levels. The serum IgE
      level was significantly higher in the AD group. The SCORAD index was correlated
      with serum IgE level. Conclusions: Basal serum cortisol and ACTH levels are
      normal in AD patients. Serum IgE level is significantly higher in AD patients and
      is correlated with the disease severity.

PMID- 29214107
TI  - Diet and rosacea: the role of dietary change in the management of rosacea.
AB  - Dietary change may play a role in the therapy of rosacea. Certain foods and
      beverages may act as "triggers" for rosacea exacerbations. These may be divided
      into heat-related, alcohol-related, capsaicin-related, and cinnamaldehyde
      related. One potential pathogenic mechanism may be via the activation of
      transient receptor potential cation channels, which result in neurogenic
      vasodilatation. Further research is needed on the role of the gut skin connection
      in rosacea. Epidemiologic studies suggest that patients with rosacea have a
      higher prevalence of gastrointestinal disease, and one study reported improvement
      in rosacea following successful treatment of small intestinal bacterial
      overgrowth. While further research is required in this area, patients may be
      advised on measures to support a healthy gut microbiome, including the
      consumption of a fiber-rich (prebiotic) diet.

PMID- 29214108
TI  - Reflectance confocal microscopy of an inverted follicular keratosis mimicking a
      squamous cell carcinoma.
AB  - Distinguishing between benign and malignant neoplasms of the skin is a daily
      challenge to dermatologists. With the use of a dermatoscope and other imaging
      devices, the diagnosis is often more precise. The confocal microscope is a device
      that uses a near-infrared laser to perform noninvasive imaging of the skin. The
      benefit is that the images immediately provide additional, cellular-level
      information that can assist in diagnosis. However, lesions may share overlapping
      characteristics on confocal microscopy, and hence, benign lesions can still
      display confocal features concerning for a cancerous process, justifying a
      biopsy. Here, we present a case of an inverted follicular keratosis imitating a
      squamous cell carcinoma on confocal microscopy.

PMID- 29214109
TI  - A solitary pink lesion: dermoscopy and RCM features of lichen planus.
AB  - We present an unusual onset of cutaneous lichen planus (LP) in a middle-aged
      patient. The initial presentation as solitary, indolent pink lesion required
      further investigations to rule out malignancy, especially amelanotic melanoma.
      Dermoscopy and reflectance confocal microscopy findings were found to be helpful
      in our case in addressing the correct diagnosis.

PMID- 29214110
TI  - Dermoscopy of multiple warty dyskeratomas.

PMID- 29214111
TI  - Examining the factors associated with past and present dermoscopy use among
      family physicians.
AB  - Introduction: Family physicians (FPs) play a critical role in the early detection
      of skin cancers. Dermoscopy can improve diagnostic accuracy but its use by FPs in
      the United States (US) remains understudied. Objectives: To examine dermoscopy
      use, factors associated with ever having used (Model 1) and currently using the
      dermascope (Model 2), and barriers. Methods: We recruited 705 practicing FPs in
      person at conferences and on-line to complete an anonymous, 46 item survey
      measuring: demographic factors, physician and practice characteristics;
      confidence in differentiating skin lesions; knowledge and use of dermoscopy;
      intentions to use; and barriers to use. We conducted bivariate analysis for each
      outcome and entered the significant predictors into two logistic regressions.
      Results: Almost 20% had ever used a dermascope and 8.3% were currently using it.
      Ever having used a dermascope was associated with being 39 years of age or
      younger, practicing in academia or community centers, and having higher
      confidence differentiating skin lesions. Current use was associated with seeing
      more than 400 patients per month and being 60 years-of-age or older. Conclusion:
      Use of dermoscopy by FPs is low. This study is an initial step in understanding
      its use among US FPs.

PMID- 29214112
TI  - Hypomelanotic melanoma detected by the "little red riding hood sign" in a patient
      with neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is a genetic disorder commonly associated with an
      increased risk for development of malignancy, including skin cancers. Herein we
      describe a case of invasive melanoma occurring in a patient with NF1 and discuss
      the association between these two diseases, highlighting the importance of
      comparative clinical and dermoscopic approaches in this category of patients in
      which the detection of melanoma can be difficult because of the presence of
      multiple skin tumors.

PMID- 29214113
TI  - Reflectance confocal microscopy of mammary Paget disease.
AB  - Mammary Paget disease is the intraepidermal adenocarcinoma of the nipple area
      which is characterized usually by a well-demarcated eczematous plaque.
      Reflectance confocal microscopy (RCM), is an in vivo noninvasive diagnostic tool
      with a high-resolution imaging of the skin, almost comparable to conventional
      histology. RCM findings of Paget disease are limited in the literature. Most of
      the reported cases are the extramammary type. In this report, we aimed to
      evaluate the RCM findings of a non-pigmented mammary Paget disease in a 65 year
      old woman.

PMID- 29214115
TI  - Morphology Under Control: Engineering Biodegradable Stomatocytes.
AB  - Biodegradable nanoarchitectures, with well-defined morphological features, are of
      great importance for nanomedical research; however, understanding (and thereby
      engineering) their formation is a substantial challenge. Herein, we uncover the
      supramolecular potential of PEG-PDLLA copolymers by exploring the physicochemical
      determinants that result in the transformation of spherical polymersomes into
      stomatocytes. To this end, we have engineered blended polymersomes (comprising
      copolymers with varying lengths of PEG), which undergo solvent-dependent
      reorganization inducing negative spontaneous membrane curvature. Under conditions
      of anisotropic solvent composition across the PDLLA membrane, facilitated by the
      dialysis methodology, we demonstrate osmotically induced stomatocyte formation as
      a consequence of changes in PEG solvation, inducing negative spontaneous membrane
      curvature. Controlled formation of unprecedented, biodegradable stomatocytes
      represents the unification of supramolecular engineering with the theoretical
      understanding of shape transformation phenomena.

PMID- 29214114
TI  - Calcium Dysregulation in Alzheimer's Disease: A Target for New Drug Development.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most
      common cause of dementia among aged people whose population is rapidly
      increasing. AD not only seriously affects the patient's physical health and
      quality of life, but also adds a heavy burden to the patient's family and
      society. It is urgent to understand AD pathogenesis and develop the means of
      prevention and treatment. AD is a chronic devastating neurodegenerative disease
      without effective treatment. Current approaches for management focus on helping
      patients relieve or delay the symptoms of cognitive dysfunction. The calcium ion
      (Ca2+) is an important second messenger in the function and structure of nerve
      cell circuits in the brain such as neuronal growth, exocytosis, as well as in
      synaptic and cognitive function. Increasing numbers of studies suggested that
      disruption of intracellular Ca2+ homeostasis, especially the abnormal and
      excessive Ca2+ release from the endoplasmic reticulum (ER) via the ryanodine
      receptor (RYR), plays important roles in orchestrating the dynamic of the
      neuropathology of AD and associated memory loss, cognitive dysfunction.
      Dantrolene, a known antagonist of the RYR and a clinically available drug to
      treat malignant hyperthermia, can ameliorate the abnormal Ca2+ release from the
      RYR in AD and the subsequent pathogenesis, such as increased beta-secretase and
      gamma-secretase activities, production of Amyloid-beta 42 (Abeta 42) and its
      oligomer, impaired autophagy, synapse dysfunction, and memory loss. However, more
      studies are needed to confirm the efficacy and safety repurposing dantrolene as a
      therapeutic drug in AD.

PMID- 29214116
TI  - Compassionate use of ruxolitinib in acute and chronic graft versus host disease
      refractory both to corticosteroids and extracorporeal photopheresis.
AB  - Background: Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in
      myelofibrosis. In recent years, research in graft versus host disease (GVHD) has
      revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some
      reports have shown significant responses in refractory GVHD patients. Cases
      presentation: In this report we present our experience in 8 patients with acute
      or chronic GVHD with refractoriness to steroids and extracorporeal photopheresis
      treated with ruxolitinib. Three patients had acute GVHD (1 pulmonary, 2
      cutaneous, 1 multi-systemic) and 5 had chronic GVHD (3 cutaneous); 85% obtained
      an overall response and 50% a complete response with a tolerable toxicity
      profile. Conclusions: In our series, Ruxolitinib was very active as a rescue
      therapy for patients with acute or chronic GVHD refractory to standard treatment.

PMID- 29214117
TI  - Broadband Dielectric Spectroscopic Characterization of Thermal Stability of Low-k
      Dielectric Thin Films for Micro- and Nanoelectronic Applications.
AB  - In this paper, we discuss the use of broadband microwaves (MW) to characterize
      the thermal stability of organic and hybrid silicon-organic thin films meant for
      insulation applications in micro- and nanoelectronic devices. We take advantage
      of MW propagation characteristics to extract and examine the relationships
      between electrical properties and the chemistry of prototypical low-k materials.
      The impact of thermal anneal at modest temperatures is examined to shed light on
      the thermal-induced performance and reliability changes within the dielectric
      films. These changes are then correlated with the chemical changes in the films,
      and could provide basis for rational selection of organic dielectrics for
      integrated devices.

PMID- 29214118
TI  - The plasma environment inside geostationary orbit: A Van Allen Probes HOPE
      survey.
AB  - The two full precessions in local time completed by the Van Allen Probes enable
      global specification of the near-equatorial inner magnetosphere plasma
      environment. Observations by the Helium-Oxygen-Proton-Electron (HOPE) mass
      spectrometers provide detailed insight into the global spatial distribution of
      electrons, H+, He+, and O+. Near-equatorial omnidirectional fluxes and abundance
      ratios at energies 0.1-30 keV are presented for 2 <= L <= 6 as a function of L
      shell, magnetic local time (MLT), and geomagnetic activity. We present a new tool
      built on the UBK modeling technique for classifying plasma sheet particle access
      to the inner magnetosphere. This new tool generates access maps for particles of
      constant energy for more direct comparison with in situ measurements, rather than
      the traditional constant MU presentation typically associated with UBK. We
      present for the first time inner magnetosphere abundances of O+ flux relative to
      H+ flux as a function of Kp, L, MLT, and energy. At L = 6, the O+/H+ ratio
      increases with increasing Kp, consistent with previous results. However, at L < 5
      the O+/H+ ratio generally decreases with increasing Kp. We identify a new
      "afternoon bulge" plasma population enriched in 10 keV O+ and superenriched in 10
      keV He+ that is present during quiet/moderate geomagnetic activity (Kp < 5) at
      ~1100-2000 MLT and L shell 2-4. Drift path modeling results are consistent with
      the narrow energy and approximate MLT location of this enhancement, but the
      underlying physics describing its formation, structure, and depletion during
      higher geomagnetic activity are currently not understood.

PMID- 29214119
TI  - Interested consumers' awareness of harmful chemicals in everyday products.
AB  - Background: Everyday products can contain a multitude of harmful substances
      unnoticed by most consumers, because established risk communication channels
      reach only part of the society. The question is, whether at least interested and
      informed consumers are able to use risk communication tools and assess harmful
      chemicals in products. Results: An online survey investigated the awareness of
      1030 consumers on harmful substances in everyday items. Participating consumers'
      education level, knowledge in chemistry, and motivation were above society's
      average. Although a large number of responses showed that survey participants
      were familiar with several aspects of the issue, the results revealed that
      knowledge in chemistry helped, but was not enough. Many participants assumed that
      products with an eco-label, natural personal care products, products without
      hazard pictograms or products produced in the European Union would not contain
      harmful substances. Most participants indicated to use hazard pictograms,
      information on the packaging, reports in the media, and environmental and
      consumer organizations as information sources, while information by authorities
      and manufacturers were not named frequently and did not receive high confidence.
      Smartphone applications were not indicated by many participants as information
      sources. The information sources most trusted were environmental and consumer
      organizations, hazard pictograms, and lists of ingredients on the containers. The
      declared confidence in certain risk communication instruments did not always
      correspond to the use frequencies indicated. Nearly all participants considered
      legislators as responsible for the reduction of harmful substances in consumer
      products. Conclusions: Misconceptions about harmful substances in products can be
      dangerous for the personal health and the environment. The survey indicates that
      motivation, educational level, and chemical expertise do not automatically
      provide an appropriate understanding of harmful substances in products. If well
      informed consumers are not sufficiently capable to use risk information elements
      as revealed in this study, then this will be even more the case for the general
      public. Consumer awareness should be stipulated by an improved information
      strategy about chemical risks in consumer products with an extensive
      participation of the target groups and by more efforts by authorities and
      manufactures to build trust and to provide easily understandable information.

PMID- 29214120
TI  - Immobilized aptamer on gold electrode senses trace amount of aflatoxin M1.
AB  - An electrochemical aptasensor for detection of trace amounts of aflatoxin M1 was
      developed. This required immobilization of aptamer on screen printed gold
      electrode comprising of working electrode, counter electrode and reference
      electrode and was achieved by sequentially layering dithiodipropionic acid,
      streptavidin and biotinylated-tetraethylene glycol-aptamer. Immobilization of
      aptamer was monitored by cyclic voltammetry. Peak current in square wave
      voltammogram was inversely related to logarithmic concentration of aflatoxin M1.
      Dynamic range of sensor was 1-105 ppt aflatoxin M1. Sensor can be regenerated by
      treating electrode with 10% sodium dodecyl sulfate or 40 mM tris-HCl (pH 8.0)
      containing 10 mM ethylenediaminetetraacetic acid and 0.02% tween-20.

PMID- 29214121
TI  - Towards One-Step Quantitation of Prostate-Specific Antigen (PSA) in Microfluidic
      Devices: Feasibility of Optical Detection with Nanoparticle Labels.
AB  - Rapid and quantitative prostate-specific antigen (PSA) biomarker detection would
      be beneficial to cancer diagnostics, improving early detection and therefore
      increasing chances of survival. Nanoparticle-based detection is routinely used in
      one-step nitrocellulose-based lateral flow (LF) immunoassays; however, it is well
      established within the scientific diagnostic community that LF technology lacks
      sensitivity for measuring biomarkers, such as prostate-specific antigen (PSA). A
      trend in point-of-care (POC) protein biomarker quantitation is the
      miniaturization of immunoassays in microfluidic devices. This work aimed at
      testing the feasibility of carbon and gold nanoparticles as immunoassay labels
      for PSA detection with cost-effective optical detection in a novel microfluidic
      POC platform called microcapillary film (MCF), consisting of a parallel array of
      fluoropolymer microcapillaries with 200-MUm internal diameter. With neutravidin
      coated carbon, nanoparticles were able to quantify an immobilized biotinylated
      monoclonal antibody (coating solution from 10 to 40 MUg/ml) and PSA was
      successfully quantified in a sandwich assay using silver-enhanced gold
      nanoparticles and a flatbed scanner; yet, the dynamic range was limited to 10-100
      ng/ml. Although direct optical detection of PSA without enzymatic amplification
      or fluorophores is possible and technically appealing for the simplified fluidics
      and signal scanning setups involved, ultimately, the binding of a thin layer of
      nanoparticles onto the wall of transparent microcapillaries is not sufficient to
      cause a significant drop on the optical colorimetric signal. Future studies will
      explore the use of fluorescence nanoparticles.

PMID- 29214123
TI  - Pay for performance - motivation to succeed in Advanced Trauma Life Support
      courses - a question of background or funding?
AB  - Objective: To correlate students' performance with their professional background
      and motivation to take part in Advanced Trauma Life Support (ATLS) courses. We
      base our analysis on the self-determination theory that differentiates intrinsic
      (ambition to perform by individual itself) from extrinsic motivation (incentive
      by external stimuli). Design: We present a non-blinded, monocentric, non
      randomized descriptive study of 376 students taking part in an ATLS course at one
      course site in Germany. Part of a two-day ATLS course are two written tests; we
      correlate test scores with background information provided by the students in a
      questionnaire of 13 items (age, sex, adress, board certification, specialty,
      subspecialty, position, hospital level of care, hospital operator and hospital
      participation in trauma network, motivation, funding source, condition of
      funding). Setting: The students were recuited at the BG Trauma Center
      Ludwigshafen (Germany), a large 528-bed trauma center and one of 13 ATLS course
      sites in Germany. Participants: 449 ATLS course students taking part in ATLS
      courses at the above-mentioned course site from February 2009 to May 2010 were
      sent a questionnaire asking for their background. All 449 course students were
      eligible to participate. 376 (83.7%) questionnaires were returned, pre- and post
      test results of all students aquired and included into our calculations. 312
      (83%) were male and 64 (17%) female. The majority (59.3%) of recruited students
      came from trauma surgery, 21.8% from anesthesiology, 8% from general surgery, 4%
      from abdominal surgery, 0.5% from vascular or thoracic surgery each and 5.9% from
      other specialties. Results: Neither age, sex, subspecialty, hospital level of
      care, hospital operator, or hospital participation in trauma network played a
      role with respect to motivation or test results. The high degree of intrinsic
      motivation of consultants (92.3%) had no impact on their test results.
      Anesthesiologists were higher motivated (75.6% intrinsically motivated) in
      contrast to all surgical colleagues (63.6%), which showed significant differences
      in the pre- (89.8% vs. 85.3%, p=0.03) but not the post-test. Of all 13.6%
      students who were self-payers, 94.1% were intrinsically motivated; the 86.2%
      whose course fee was accounted for were less likely to be intrinsically motivated
      (63.9%). Sponsoring however did not have a negative impact on test results.
      Conditional funding (sponsored only on passing both tests) was detrimental to
      motivation: 0% of these individuals were intrinsically motivated and they scored
      significantly lower (82.5%) than all other students in the post-test (86.9%,
      p=0.002). Overall, intrinsically motivated students overtopped extrinsically
      motivated students in the post-test (88.0% vs. 83.4%, p<0.001). Conclusions: ATLS
      course participation is not compulsory for medical doctors in Germany. Intrinsic
      motivation to take part in these courses is a key prerequisite to increase
      performance, irrespective of the background of the students. Intrinsically
      motivated students are ready to invest into their education and vice versa.
      Conditional funding (course fee only sponsored on passing the course) evokes no
      intrinsic motivation at all and causes worse results.

PMID- 29214122
TI  - Peripheral nerve sheath tumors of the upper extremity and hand in patients with
      neurofibromatosis type 1: topography of tumors and evaluation of surgical
      treatment in 62 patients.
AB  - Objective: Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor
      predisposition syndrome with a tendency to develop peripheral nerve sheath tumors
      (PNST). Plexiform neurofibromas (PNF) are detected in a high proportion of
      affected patients. The tumors can lead to severe disfigurement and are classified
      as precancerous. This study examines the surgical procedures that have been
      performed on large PNST of the upper limb and hand, and investigates whether a
      specific distribution pattern of the tumors can be detected in surgically treated
      cases. Methods: Surgical procedures on the upper extremity and hand performed on
      patients with NF1 were evaluated at an interval of 25 years (1992-2016).
      Topography of the tumors was classified according to dermatomes. The number of
      interventions per patient, duration of operations, and complications of the
      interventions were registered. An overview of the surgical treatment of PNST of
      the upper limb and hand was obtained from the literature, with special
      consideration of the genetic background of treated tumors. Results: One hundred
      and sixty-three surgical interventions on the upper limb and hand were performed
      in 62 patients with NF1 for the treatment of large PNST, predominantly PNF (age:
      mean value: 27.33 years, male: 33, female: 29; right side: 25, left side: 26,
      bilateral: 7). Surgical procedures lasted an average of 72.47 minutes. In
      approximately half of the patients, one surgical procedure was sufficient.
      Duration of stay in hospital was on average 7-11 days. Neurological complications
      were rarely noted and occurred only temporarily. There were no dermatomes
      affected by PNF with particular frequency. However, some dermatomes were more
      often simultaneously affected by a PNF at the same time as others. Conclusion:
      Although the distribution pattern shows some accumulation of tumor localization,
      tumors are distributed evenly and show very variable size and extent in
      individual cases. Surgical treatment of PNF of the upper limb and hand helps
      alleviate the physical discomfort that these patients have from their disfiguring
      disease. Repeated interventions are necessary relatively often in order to adapt
      the tumorous region to the outline of the limb and to improve its function.

PMID- 29214124
TI  - Culture and emotion perception: comparing Canadian and Japanese children's and
      parents' context sensitivity.
AB  - Prior research on the perception of facial expressions suggests that East Asians
      are more likely than North Americans to incorporate the expressions of background
      figures into their judgment of a central figure's emotion (Masuda et al. in J
      Pers Soc Psychol 94:365-381, 2008b). However, little research has examined this
      issue in the context of developmental science, especially during joint sessions
      where parents engage in a task in front of their 7-8-year-old children. In this
      study, 22 Canadian and 20 Japanese child-parent dyads participated in an emotion
      judgment task, and were asked to judge a central figure's emotion and explain
      their reasoning. The results indicated that while early elementary school
      children did not show culturally dominant reasoning styles, parents displayed
      culturally dominant modes of attention, serving as models for their children.

PMID- 29214125
TI  - Toward Wearable Energy Storage Devices: Paper-Based Biofuel Cells based on a
      Screen-Printing Array Structure.
AB  - A novel paper-based biofuel cell with a series/parallel array structure has been
      fabricated, in which the cell voltage and output power can easily be adjusted as
      required by printing. The output of the fabricated 4-series/4-parallel biofuel
      cell reached 0.97+/-0.02 mW at 1.4 V, which is the highest output power reported
      to date for a paper-based biofuel cell. This work contributes to the development
      of flexible, wearable energy storage device.

PMID- 29214127
TI  - In situ synthesis of silver nanoparticles on the surface of PDMS with high
      antibacterial activity and biosafety toward an implantable medical device.
AB  - We developed a straightforward method to fabricate antibacterial silicon films
      via the in situ synthesis of silver nanoparticles (AgNPs) on a
      polydimethylsiloxane (PDMS) film. To grow AgNPs attached on the film, AgNP seeds
      were synthesized through the reduction of silver ions electrostatically bound to
      hydroxyl groups formed on the surface of the film after treatment with air
      plasma. In the growth reaction, silver ions were reduced on the seeds of AgNPs by
      sodium citrate in a solution of AgNO3, which allowed for the formation of AgNPs
      with sizes of up to ~ 500 nm, which The formed AgNPs on the films were
      characterized using UV-vis spectrophotometer, scattering electron microscope and
      induced coupled mass spectrometer. The amount of AgNPs was estimated to be less
      than 0.05% of the total film weight. Even though it was coated with a small
      amount of AgNPs, the PDMS film exhibited reduction of E. coli and S. aureus with
      values of log10 4.8 and log10 5.7, respectively. The biosafety of the AgNP
      attached PDMS film was examined by contact of cells with the film or film eluent.
      Counting of viable cells revealed no significant cytotoxicity of the in situ
      fabricated AgNPs on the PDMS film.

PMID- 29214126
TI  - Pharmacologic Complement Inhibition in Clinical Transplantation.
AB  - Purpose of Review: Over the past two decades, significant strides made in our
      understanding of the etiology of antibody-mediated rejection (AMR) in
      transplantation have put the complement system in the spotlight. Here, we review
      recent progress made in the field of pharmacologic complement inhibition in
      clinical transplantation and aim to understand the impact of this therapeutic
      approach on outcomes in transplant recipients. Recent Findings: Encouraged by the
      success of agents targeting the complement cascade in disorders of unrestrained
      complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical
      hemolytic uremic syndrome (aHUS), investigators are testing the safety and
      efficacy of pharmacologic complement blockade in mitigating allograft injury in
      conditions ranging from AMR to recurrent post-transplant aHUS, C3
      glomerulopathies and antiphospholipid anti-body syndrome (APS). A recent
      prospective study demonstrated the efficacy of terminal complement inhibition
      with eculizumab in the prevention of acute AMR in human leukocyte antigen (HLA)
      incompatible living donor renal transplant recipients. C1 esterase inhibitor (C1
      INH) was well tolerated in two recent studies in the treatment of AMR and was
      associated with improved renal allograft function. Summary: Pharmacologic
      complement inhibition is emerging as valuable therapeutic tool, especially in the
      management of highly sensitized renal transplant recipients. Novel and promising
      agents that target various elements in the complement cascade are in development.
      Graphical Abstract?.

PMID- 29214128
TI  - A Clinic-Based Assessment for Evaluating Job-Related Social Skills in Adolescents
      and Adults with Autism.
AB  - Many individuals with autism spectrum disorder (ASD) have difficulties obtaining
      and maintaining employment, yet little research has evaluated methods for
      assessing and improving critical vocational skills. In this study, we evaluated
      an assessment of job-related social skills for individuals with ASD by arranging
      conditions that simulated on-the-job experiences in a clinic setting. The
      experimenter contrived situations to assess a variety of social skills, including
      asking for help, asking for more materials, and responding to corrective
      feedback. A total of eight individuals, aged 16 to 32 years, participated.
      Results suggested that the assessment was useful for identifying specific social
      skills that could be targeted for intervention to increase success in the work
      environment. These findings add to the current literature by demonstrating an
      objective method for assessing a variety of job-related social skills under
      controlled, naturalistic conditions.

PMID- 29214129
TI  - Using Multiple Exemplar Training to Teach Empathy Skills to Children with Autism.
AB  - The purpose of the study was to use multiple exemplar training to teach
      empathetic responding to two children with autism. Three emotions-happiness,
      frustration and sadness/pain-were chosen for this purpose. Treatment consisted of
      verbal prompting and reinforcement of empathetic responses. Four experimenter
      defined categories with discriminative stimuli were used for each emotion. The
      multiple exemplar component of the model consisted of teaching responses in the
      presence of several discriminative stimuli drawn from the predefined categories
      for each emotion delivered by two persons across two environments. Results were
      evaluated using a multiple baseline design across behaviours and indicate a
      systematic increase in responses with the introduction of treatment across each
      category for both participants. Generalization of responses from training to non
      training stimuli in both participants was observed during probe trials and was
      maintained during follow-up probes.

PMID- 29214130
TI  - Measuring Adherence to a Nutrition and Exercise Lifestyle Intervention: Is
      Program Adherence Related to Excessive Gestational Weight Gain?
AB  - To identify adherence required to achieve target health outcome(s) in nutrition
      and/or exercise interventions, a measurement tool that tracks objective and self
      reported measures of adherence is necessary. The purpose of this study was to
      design an adherence measurement tool and test it retrospectively on the Nutrition
      and Exercise Lifestyle Intervention Program (NELIP; Ruchat et al., Medicine and
      Science in Sports and Exercise, 44(8), 1419-1426, 2012; Mottola et al., Medicine
      and Science in Sports and Exercise, 42(2), 265-272, 2010), designed to prevent
      excessive gestational weight gain (EGWG). The tool was based on the goals of the
      NELIP and included a grading system for each behavior (exercise and nutrition).
      It was used to determine whether adherence scores could differentiate excessive
      versus acceptable weight gain during pregnancy across pre-pregnancy body mass
      index (BMI) categories. Results showed irrespective of pre-pregnancy BMI, women
      with acceptable weight gain had significantly higher adherence (p < 0.05) than
      women with excessive weight gain. It is recommended that this adherence tool be
      included in future prospective lifestyle intervention studies.

PMID- 29214131
TI  - The Use of Behavioral Skills Training to Teach Graph Analysis to Community Based
      Teachers.
AB  - In this study, the experimenter trained three teachers to implement data decision
      rules to detect when instructional changes should be made during the visual
      analysis of discrete-trial percentage graphs. The experimenter used a concurrent,
      multiple-baseline design across participants. The experimenter trained the
      teachers to follow decision-making rules using instruction, modeling, rehearsal,
      and feedback. Following intervention, participants increased the percentage of
      correct data-based decisions and decreased the percentage of errors.

PMID- 29214132
TI  - Practice Recommendations for Addressing Problem Behaviors in Siblings with Autism
      Spectrum Disorder.
AB  - Children with autism spectrum disorder (ASD) display an increased prevalence of
      problem behavior, relative to the typically developing population. Given the
      heritability of ASD and its growing prevalence, clinicians who implement
      behavioral treatments are likely to encounter families with siblings with ASD who
      exhibit problem behavior. Thus, there is a need for guidance for treatment of
      problem behavior for these families. This paper presents strategies for
      conducting behavioral assessments, developing treatments for problem behaviors,
      caregiver training, and generalization strategies when there are multiple
      affected children in one family. A case study is presented to illustrate the key
      clinical decisions made to increase the likelihood of a successful treatment
      outcome for these families.

PMID- 29214133
TI  - Systematic Review of Functional Analysis and Treatment of Elopement (2000-2015).
AB  - Elopement is a dangerous behavior that is emitted by a large proportion of
      individuals with intellectual and developmental disabilities. Functional analysis
      and function-based treatments are critical in identifying maintaining reinforcers
      and decreasing elopement. The purpose of this review was to identify recent
      trends in the functional analysis and treatment of elopement, as well as
      determine the efficacy (standardized mean differences) of recent treatments. Over
      half of subjects' elopement was maintained by social positive reinforcement,
      while only 25% of subjects' elopement was maintained by social negative
      reinforcement. Elopement was rarely maintained by automatic reinforcement, and
      none of the studies in the current review evaluated treatments to address
      automatically maintained elopement. Functional communication training was the
      most common intervention regardless of function. Results are discussed in terms
      of clinical implications and directions for future research.

PMID- 29214134
TI  - A Response to Papatola and Lustig's Paper on Navigating a Managed Care Peer
      Review: Guidance for Clinicians Using Applied Behavior Analysis in the Treatment
      of Children on the Autism Spectrum.
AB  - In their 2016 article, "Navigating a Managed Care Peer Review: Guidance for
      Clinicians Using Applied Behavior Analysis [ABA] in the Treatment of Children on
      the Autism Spectrum," Papatola and Lustig provide an overview of the managed care
      process, discuss the medical necessity of ABA, and offer guidance to clinicians
      on how to navigate the managed care peer review process. Given that the authors
      are employed by a large international health insurance carrier and conduct peer
      reviews on behalf of that organization, this response seeks to provide guidance
      from both the clinical and public policy perspectives that reflect best practices
      in the field of autism treatment. This response is not written with the intention
      of providing or replacing legal advice; rather, this paper offers health care
      providers of ABA an essential understanding of some of the laws that govern and
      support their efforts to secure medically necessary treatment and the mechanisms
      in place with which to challenge decisions by managed care organizations, health
      plans, and health insurance issuers that may be contrary to best practices.
      Finally, suggestions are offered on how to navigate a peer review to ensure
      optimal outcomes and, when necessary, to lay the groundwork to overturn a funding
      source decision that does not reflect best practices or the standard of care in
      ABA-based autism treatment.

PMID- 29214135
TI  - Developing Procedures to Improve Therapist-Child Rapport in Early Intervention.
AB  - Rapport is a primary component in the development of a therapeutic relationship
      between health-service professionals and clients. Presession pairing is a
      procedure often recommended in behavior analytic practice to build rapport with
      clients. However, many service providers may not exhibit presession pairing
      skills correctly or at a sufficient rate. The current study aimed to
      operationally define therapist behaviors that are indicative of presession
      pairing and to train direct care staff to implement said skills.

PMID- 29214136
TI  - Training Parents in Saudi Arabia to Implement Discrete Trial Teaching with their
      Children with Autism Spectrum Disorder.
AB  - The present study evaluates the effects of a behavioral skill training package on
      parent implementation of discrete trial teaching with their children with autism
      spectrum disorder. Three mothers of children with autism participated in the
      study. The training package improved implementation for all three of the mothers.
      Moreover, these improvements generalized to skills that were not taught during
      training, maintained during follow-up probes, and resulted in improvements in
      child behavior.

PMID- 29214137
TI  - Speak Up: Increasing Conversational Volume in a Child with Autism Spectrum
      Disorder.
AB  - Deficits in social interactions are a hallmark of autism spectrum disorder. This
      study examined one relatively uncommon aspect of social interactions that has not
      received much attention from the literature: appropriate conversational volume.
      Conversational speech volume was measured using a commercially available
      application, and a package intervention was developed that consisted of feedback
      from the voice measuring application, signaling from a wrist bracelet, and
      differential reinforcement. The intervention was evaluated in an ABAB design and
      speaking at conversational volume was significantly increased when the
      intervention was in place and in probe conditions.

PMID- 29214138
TI  - Treating Food Approval-Seeking Behavior: One Bite at a Time.
AB  - The prevalence of feeding problems in children with autism is high. The current
      investigation was a treatment of a unique presentation of food-related prompt
      dependence with a 6-year-old boy with autism who was reliant upon approval from
      adults for consumption of every bite of food. Instructions were used to establish
      independent eating, in which the number of bites specified in the instruction was
      systematically increased. Independent bites increased from a baseline level of
      0.67% to a final phase level of almost 100%, and the instruction was faded to
      "eat your lunch".

PMID- 29214139
TI  - The Effects of Advance Notice on Problem Behavior Occasioned by Interruptions of
      an Ongoing Activity in a Young Girl with Autism.
AB  - The current study describes a trial-based functional analysis of problem behavior
      conducted in a home setting for a 7-year-old girl with autism. Problem behavior
      was occasioned by interruptions to an ongoing activity. Advance notice, in the
      form of a 2-min warning, and the sound of a timer were used to signal termination
      of a current activity and were effective at reducing problem behavior along with
      increasing compliance to the interruptive demands. A trial-based functional
      analysis, which are not common in the applied literature, was conducted in a home
      setting for young girl with autism, using antecedent and consequence
      modifications described by Hagopian, Bruzek, Bowman, and Jennett (2007),
      identified the variables that occasioned and maintained problem behavior were
      interruptions to an ongoing activity followed by regaining uninterrupted access
      to the previous activity. Mixed findings have been reported regarding the
      effectiveness of advance notice for decreasing problem behavior. Results of the
      current study show that an advance notice treatment package was effective for a
      child with autism; no escape extinction was necessary. Interruptions are part of
      everyday life and tolerating these changes is critical for habilitation for
      individuals with autism.

PMID- 29214140
TI  - Teacher-Conducted, Latency-Based Functional Analysis as Basis for Individualized
      Levels System in a Classroom Setting.
AB  - Latency-based functional analysis (FA) may be appropriate when stakeholders are
      concerned with safety or feasibility. We trained a first-year special education
      teacher to collect data while she implemented a latency-based FA and validated a
      function-based intervention. Treatment effects were generalized across
      paraeducators and were maintained during a 1-month follow-up.

PMID- 29214141
TI  - New trends in anaphylaxis.
AB  - This review presents the current trends in anaphylaxis management discussed at
      the fourth International Network for Online-Registration of Anaphylaxis (NORA)
      conference held in Berlin in April 2017. Current data from the anaphylaxis
      registry show that Hymenoptera venom, foods, and pharmaceutical drugs are still
      among the most frequent triggers of anaphylaxis. Rare triggers include chicory,
      cardamom, asparagus, and goji berries. A meta-analysis on recent trends in insect
      venom anaphylaxis demonstrated for the first time that, although data on the
      efficacy of insect venom immunotherapy is limited, the occurrence of severe
      reactions upon repeated sting events can be prevented and patients' quality of
      life improved. Molecular diagnostics of insect venom anaphylaxis have
      significantly improved diagnostic sensitivity and specificity. Self-treatment of
      anaphylaxis is of great importance. Recent data from the anaphylaxis registry
      show an increase (from 23% in 2012 to 29% in 2016) in the use of adrenaline as
      recommended in the guidelines. A survey on the implementation of guidelines
      conducted among the centers reporting to the anaphylaxis registry highlights the
      extent to which the guideline has been perceived and implemented. Reports on a
      variety of cases in the anaphylaxis registry illustrate the diversity of this
      potentially life-threatening reaction. Component-resolved diagnostics can help to
      specify sensitization profiles in anaphylaxis, particularly in terms of the risk
      for severe reactions. Recent studies on anaphylaxis awareness show that training
      methods are effective; nevertheless, target groups and learning methods need to
      undergo further scientific investigation in coming years.

PMID- 29214142
TI  - Molecular Mechanisms of Enzalutamide Resistance in Prostate Cancer.
AB  - Purpose of Review: Compensatory mechanisms leading to increased androgen receptor
      expression and activity after androgen ablation or anti-androgen treatment have
      been identified in prostate cancer. After hydroxyflutamide and bicalutamide were
      used in therapy of prostate cancer over many years, novel anti-androgen
      enzalutamide showed improved clinical activity. However, enzalutamide resistance
      develops over a certain time period, and molecular mechanisms responsible for
      this process are heterogeneous. Research Findings: As with other anti-androgens,
      these mechanisms include alterations of AR but also may be associated with
      overexpression of oncogenes which should be targeted by novel therapies. Androgen
      receptor splice variants have been frequently described in patients who developed
      enzalutamide resistance. Mutant AR F876L has been detected in patients who are
      resistant to enzalutamide. Glucocorticoid receptor overexpression has been
      observed in patient tissues and in pre-clinical models of enzalutamide
      resistance. Summary: There is a heterogeneous picture of enzalutamide resistance
      in prostate cancer and, therefore, the development of appropriate post
      enzalutamide treatment remains a challenge.

PMID- 29214144
TI  - Trajectories of emigrant quasi-citizenship: a comparative study of Mexico and
      Turkey.
AB  - In two of the busiest migration corridors of the twentieth century, namely Mexico
      US and Turkey-Germany, migrants can today be dual citizens. However, the
      acceptance of dual citizenship did not occur automatically; instead, it followed
      a period of legal statuses short of full citizenship. This paper conceptualises
      such statuses as quasi-citizenship, a transitional equilibrium between the
      absence of plural citizenship and the existence of transnational migration.
      Focusing on sending states, the emergence of emigrant quasi-citizenship is thus
      explained, first, in terms of whether the reciprocal regimes of emigration and
      immigration states diverge on the acceptance of plural citizenship. Second, the
      stance towards plural citizenship is explained in terms of the experience with
      emigration. It is then shown that, in the case of Mexico, the legacy of undesired
      emigration weakened the incentives to adapt the territorial conception of
      citizenship to expatriates, hence creating quasi-citizens, and in the case of
      Turkey, the higher political relevance of expatriates, who could have the host
      country citizenship, reinforced the external dimension of the ethno-cultural
      conception of citizenship.

PMID- 29214143
TI  - The Potential of microRNAs for Stem Cell-based Therapy for Degenerative Skeletal
      Diseases.
AB  - Purpose of Review: Degenerative skeletal disorders including osteoarthritis (OA)
      and osteoporosis (OP) are the result of attenuation of tissue regeneration and
      lead to painful conditions with limited treatment options. Preventative measures
      to limit the onset of OA and OP remain a significant unmet clinical need.
      MicroRNAs (miRNAs) are known to be involved in the differentiation of stem cells,
      and in combination with stem cell therapy could induce skeletal regeneration and
      potentially prevent OA and OP onset. Recent Findings: The combination of stem
      cells and miRNA has been successful at regenerating the bone and cartilage in
      vivo. MiRNAs, including miR-146b known to be involved in chondrogenic
      differentiation, could provide innovative targets for stem cell-based therapy,
      for the repair of articular cartilage defects forestalling the onset of OA or in
      the generation of a stem cell-based therapy for OP. Summary: This review
      discusses the combination of skeletal stem cells (SSCs) and candidate miRNAs for
      application in a cell-based therapy approach for skeletal regenerative medicine.

PMID- 29214145
TI  - Bitter orange (Citrus aurantium L.) extract subchronic 90-day safety study in
      rats.
AB  - Bitter orange (Citrus aurantium L.) extracts are widely used in dietary
      supplements and bitter oranges are used in various juices and food products. p
      Synephrine, the primary active constituent, comprises approximately 90% of total
      protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day
      subchronic safety/toxicity of an extract standardized to 50% p-synephrine at
      doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects
      were observed with respect to any of the observed parameters of clinical signs,
      functional observations of sensory reactivity, grip strength and motor activity,
      ophthalmology, body weights, hematology, food consumption, urinalysis, organ
      weights, as well as gross and microscopic pathology at termination at any of the
      doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract
      resulted in non-adverse effects including fully reversible signs of repetitive
      head burrowing in the bedding material and piloerection for short periods of time
      in both sexes immediately after administration, which gradually disappeared by
      treatment day-81. A slight and reversible elevation of BUN and urea levels in
      male rats, and slight to mild increase in the relative but not absolute heart
      weights of male and female rats was observed. Based on these results, the no
      observed-effect-level (NOEL) for this bitter orange extract standardized to 50% p
      synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL) was
      1000 mg/kg. The results indicate a high degree of safety for this bitter orange
      extract.

PMID- 29214146
TI  - MicroRNAs and toxicology: A love marriage.
AB  - With the dawn of personalized medicine, secreted microRNAs (miRNAs) have come
      into the very focus of biomarker development for various diseases. MiRNAs fulfil
      key requirements of diagnostic tools such as i) non or minimally invasive
      accessibility, ii) robust, standardized and non-expensive quantitative analysis,
      iii) rapid turnaround of the test result and iv) most importantly because they
      provide a comprehensive snapshot of the ongoing physiologic processes in cells
      and tissues that package and release miRNAs into cell-free space. These
      characteristics have also established circulating miRNAs as promising biomarker
      candidates for toxicological studies, where they are used as biomarkers of drug-,
      or chemical-induced tissue injury for safety assessment. The tissue-specificity
      and early release of circulating miRNAs upon tissue injury, when damage is still
      reversible, are main factors for their clinical utility in toxicology. Here we
      summarize in brief, current knowledge of this field.

PMID- 29214148
TI  - Comparison of Functional Outcome after Extended versus Super-Extended Pelvic
      Lymph Node Dissection during Radical Prostatectomy in High-Risk Localized
      Prostate Cancer.
AB  - Background: Urinary continence and erectile function (EF) are best preserved when
      meticulous dissection of prostate and nerve sparing technique are used during
      radical prostatectomy (RP). However, extent of lymph node dissection (LND) may
      also adversely affect functional results. Objective: To determine whether
      performing a super-extended LND (seLND) has a significant effect on recovery of
      urinary continence and EF after RP. Design setting and participants: All patients
      who underwent RP from January 2007 until December 2013 were handed questionnaires
      assessing continence and EF. All patients in whom at least an extended LND (eLND)
      was performed were selected. This search yielded 526 patients. 172 of these
      patients had filed out 2 or more questionnaires and were included in our
      analysis. Outcome measurements and statistical analysis: All questionnaires were
      reviewed. We used Kaplan-Meier analyses and multivariate Cox analysis to assess
      the difference in recovery of continence and EF over time for eLND/seLND. Primary
      endpoints were full recovery of continence (no loss of urine) and full recovery
      of EF (successful intercourse possible). Patients who did not reach the endpoint
      when the last questionnaire was filled out were censored at that time. Median
      follow-up was 12.43 months for continence, and 18.97 months for EF. Results and
      limitations: Patients undergoing seLND have a lower chance of regaining both
      urinary continence [hazard ratio (HR) 0.59, 95% CI 0.39-0.90, p = 0.026] and EF
      (HR 0.28, 95% CI 0.13-0.57, p = 0.009). Age at surgery had a significant
      influence on both continence and EF in multivariate analysis. Major limitation of
      the study was that no formal preoperative assessment of continence and potency
      was done. Conclusion: Extending the LND template beyond the eLND template may
      cause at least a significant delay in recovery of urinary continence and leads to
      less recovery of EF.

PMID- 29214147
TI  - The Hedgehog Signaling Pathway Emerges as a Pathogenic Target.
AB  - The Hedgehog (Hh) signaling pathway plays an essential role in the growth,
      development, and homeostatis of many tissues in vertebrates and invertebrates.
      Much of what is known about Hh signaling is in the context of embryonic
      development and tumor formation. However, a growing body of evidence is emerging
      indicating that Hh signaling is also involved in postnatal processes such as
      tissue repair and adult immune responses. To that extent, Hh signaling has also
      been shown to be a target for some pathogens that presumably utilize the pathway
      to control the local infected environment. In this review, we discuss what is
      currently known regarding pathogenic interactions with Hh signaling and speculate
      on the reasons for this pathway being a target. We also hope to shed light on the
      possibility of using small molecule modulators of Hh signaling as effective
      therapies for a wider range of human diseases beyond their current use in a
      limited number of cancers.

PMID- 29214149
TI  - Measurements of Radiofrequency Radiation with a Body-Borne Exposimeter in Swedish
      Schools with Wi-Fi.
AB  - Introduction: Wireless access to the Internet is now commonly used in schools.
      Many schools give each student their own laptop and utilize the laptops and
      wireless fidelity (Wi-Fi) connection for educational purposes. Most children also
      bring their own mobile phones to school. Since children are obliged by law to
      attend school, a safe environment is important. Lately, it has been discussed if
      radiofrequency (RF) radiation can have long-term adverse effects on children's
      health. Method: This study conducted exposimetric measurements in schools to
      assess RF emissions in the classroom by measuring the teachers' RF exposure in
      order to approximate the children's exposure. Teachers in grades 7-12 carried a
      body-borne exposimeter, EME-Spy 200, in school during 1-4 days of work. The
      exposimeter can measure 20 different frequency bands from 87 to 5,850 MHz.
      Results: Eighteen teachers from seven schools participated. The mean exposure to
      RF radiation ranged from 1.1 to 66.1 uW/m2. The highest mean level, 396.6 uW/m2,
      occurred during 5 min of a lesson when the teacher let the students stream and
      watch YouTube videos. Maximum peaks went up to 82,857 uW/m2 from mobile phone
      uplink. Discussion: Our measurements are in line with recent exposure studies in
      schools in other countries. The exposure levels varied between the different Wi
      Fi systems, and if the students were allowed to use their own smartphones on the
      school's Wi-Fi network or if they were connected to GSM/3G/4G base stations
      outside the school. An access point over the teacher's head gave higher exposure
      compared with a school with a wired Internet connection for the teacher in the
      classroom. All values were far below International Commission on Non-Ionizing
      Radiation Protection's reference values, but most mean levels measured were above
      the precautionary target level of 3-6 uW/m2 as proposed by the Bioinitiative
      Report. The length of time wireless devices are used is an essential determinant
      in overall exposure. Measures to minimize children's exposure to RF radiation in
      school would include preferring wired connections, allowing laptops, tablets and
      mobile phones only in flight mode and deactivating Wi-Fi access points, when not
      used for learning purposes.

PMID- 29214150
TI  - The PhysioCam: A Novel Non-Contact Sensor to Measure Heart Rate Variability in
      Clinical and Field Applications.
AB  - Heart rate variability (HRV) is a reliable indicator of health status and a
      sensitive index of autonomic stress reactivity. Stress negatively affects
      physical and psychological wellness by decreasing cardiovascular health and
      reducing quality of life. Wearable sensors have made it possible to track HRV
      during daily activity, and recent advances in mobile technology have reduced the
      cost and difficulty of applying this powerful technique. Although advances have
      made sensors smaller and lighter, some burden on the subject remains. Chest-worn
      electrocardiogram (ECG) sensors provide the optimal source signal for HRV
      analysis, but they require obtrusive electrode or conductive material adherence.
      A less invasive surrogate of HRV can be derived from the arterial pulse obtained
      using the photoplethysmogram (PPG), but sensor placement requirements limit the
      application of PPG in field research. Factors including gender, age, height, and
      weight also affect PPG-HRV level, but PPG-HRV is sufficient to track individual
      HRV reactions to physical and mental challenges. To overcome the limitations of
      contact sensors, we developed the PhysioCam (PhyC), a non-contact system capable
      of measuring arterial pulse with sufficient precision to derive HRV during
      different challenges. This passive sensor uses an off the shelf digital color
      video camera to extract arterial pulse from the light reflected from an
      individual's face. In this article, we validate this novel non-contact measure
      against criterion signals (ECG and PPG) in a controlled laboratory setting. Data
      from 12 subjects are presented under the following physiological conditions:
      rest, single deep breath and hold, and rapid breathing. The following HRV
      parameters were validated: interbeat interval (IBI), respiratory sinus arrhythmia
      (RSA), and low frequency HRV (LF). When testing the PhyC against ECG or PPG: the
      Bland-Altman plots for the IBIs show no systematic bias; correlation coefficients
      (all p values < 0.05) comparing ECG to PhyC for IBI and LF approach 1, while RSA
      correlations average 0.82 across conditions. We discuss future refinements of the
      HRV metrics derived from the PhyC that will enable this technology to
      unobtrusively track indicators of health and wellness.

PMID- 29214151
TI  - Association between Depression and Factors Affecting Career Choice among
      Jordanian Nursing Students.
AB  - Background: Although stress reaction is high among nursing staff and nursing
      students in the Middle East and its effect on life is known, there are scant
      studies reporting on these clinical and social features. In addition, there are
      no studies reporting on factors that influence career choice among this group.
      Aim: This study aimed to investigate factors that influence career choice among
      nursing students and their possible association with depressive symptoms. Method:
      Participants were 150 (84.7% response rate) nursing students randomly selected
      from each academic year at the Nursing College/Jordan University of Science and
      Technology. Participants consented and completed the socio-demographic data
      collection sheet. The Arabic version of the Beck Depression Inventory-II Scale
      was used to assess participants with respect to depressive symptoms. A modified
      list of factors influencing career choice and a Likert scale to assess the level
      of sadness and the degree of religiosity were used as well. Results: Students
      ranked the most important three factors influencing their career selection as
      family decision, religious factors, and the desire to care for others. The
      prevalence of depression among the sample was 26%. Students who had a desire to
      care for others were less likely to suffer from depression and those who chose
      nursing as their career due to religious factors were significantly less
      depressed than those who did not. Meanwhile, students who chose nursing under
      family pressure or because of a lack of alternative opportunities were more
      depressed. The odds ratio for depressive symptoms was 0.24 when students chose
      nursing because of religious factors, whereas it was 4.92 when the family
      strongly influenced the student's career decision and 3.61 when a nursing career
      was the only perceived opportunity available. Conclusion: The main factors
      associated with depression among this sample of nursing students were pressure
      from their family to choose a nursing career and having no other career or
      employment opportunities. Religiosity was negatively associated with depression
      and may act as a protective factor; however, future studies using longitudinal
      designs will need to confirm this hypothesis.

PMID- 29214152
TI  - Identification of Candidate Casein Kinase 2 Substrates in Mitosis by Quantitative
      Phosphoproteomics.
AB  - Protein phosphorylation is a crucial regulatory mechanism that controls many
      aspects of cellular signaling. Casein kinase 2 (CK2), a constitutively expressed
      and active kinase, plays key roles in an array of cellular events including
      transcription and translation, ribosome biogenesis, cell cycle progression, and
      apoptosis. CK2 is implicated in cancerous transformation and is a therapeutic
      target in anti-cancer therapy. The specific and selective CK2 ATP competitive
      inhibitor, CX-4945 (silmitaseratib), is currently in phase 2 clinical trials.
      While many substrates and interactors of CK2 have been identified, less is known
      about CK2 substrates in mitosis. In the present work, we utilize CX-4945 and
      quantitative phosphoproteomics to inhibit CK2 activity in mitotically arrested
      HeLa cells and determine candidate CK2 substrates. We identify 330
      phosphorylation sites on 202 proteins as significantly decreased in abundance
      upon inhibition of CK2 activity. Motif analysis of decreased sites reveals a
      linear kinase motif with aspartic and glutamic amino acids downstream of the
      phosphorylated residues, which is consistent with known substrate preferences for
      CK2. To validate specific candidate CK2 substrates, we perform in vitro kinase
      assays using purified components. Furthermore, we identified CK2 interacting
      proteins by affinity purification-mass spectrometry (AP-MS). To investigate the
      biological processes regulated by CK2 in mitosis, we perform network analysis and
      identify an enrichment of proteins involved in chromosome condensation, chromatin
      organization, and RNA processing. We demonstrate that overexpression of CK2 in
      HeLa cells affects proper chromosome condensation. Previously, we found that
      phosphoprotein phosphatase 6 (PP6), but not phosphoprotein phosphatase 2A (PP2A),
      opposes CK2 phosphorylation of the condensin I complex, which is essential for
      chromosome condensation. Here, we extend this observation and demonstrate that
      PP6 opposition of CK2 is a more general cellular regulatory mechanism.

PMID- 29214153
TI  - Alzheimer's Disease Diagnosis: Discrepancy between Clinical, Neuroimaging, and
      Cerebrospinal Fluid Biomarkers Criteria in an Italian Cohort of Geriatric
      Outpatients: A Retrospective Cross-sectional Study.
AB  - Background: The role of cerebrospinal fluid (CSF) biomarkers, and neuroimaging in
      the diagnostic process of Alzheimer's disease (AD) is not clear, in particular in
      the older patients. Objective: The aim of this study was to compare the clinical
      diagnosis of AD with CSF biomarkers and with cerebrovascular damage at
      neuroimaging in a cohort of geriatric patients. Methods: Retrospective analysis
      of medical records of >=65-year-old patients with cognitive impairment referred
      to an Italian geriatric outpatient clinic, for whom the CSF concentration of
      amyloid-beta (Abeta), total Tau (Tau), and phosphorylated Tau (p-Tau) was
      available. Clinical diagnosis (no dementia, possible and probable AD) was based
      on the following two sets of criteria: (1) the Diagnostic Statistical Manual of
      Mental Disorders (DSM-IV) plus the National Institute of Neurological and
      Communicative Disorders and Stroke and the Alzheimer's Disease and Related
      Disorders Association (NINCDS-ADRDA) and (2) the National Institute on Aging
      Alzheimer's Association (NIA-AA). The Fazekas visual scale was applied when a
      magnetic resonance imaging scan was available. Results: We included 94 patients,
      mean age 77.7 years, mean Mini Mental State Examination score 23.9. The
      concordance (kappa coefficient) between the two sets of clinical criteria was
      70%. The mean CSF concentration (pg/ml) (+/-SD) of biomarkers was as follows:
      Abeta 687 (+/-318), Tau 492 (+/-515), and p-Tau 63 (+/-56). There was a trend for
      lower Abeta and higher Tau levels from the no dementia to the probable AD group.
      The percentage of abnormal liquor according to the local cutoffs was still 15 and
      21% in patients without AD based on the DSM-IV plus NINCDS-ADRDA or the NIA-AA
      criteria, respectively. The exclusion of patient in whom normotensive
      hydrocephalus was suspected did not change these findings. A total of 80% of
      patients had the neuroimaging report describing chronic cerebrovascular damage,
      while the Fazekas scale was positive in 45% of patients overall, in 1/2 of no
      dementia or possible AD patients, and in about 1/3 of probable AD patients, with
      no difference across ages. Conclusion: We confirmed the expected discrepancy
      between different approaches to the diagnosis of AD in a geriatric cohort of
      patients with cognitive impairment. Further research is needed to understand how
      to interpret this discrepancy and provide clinicians with practical guidelines.

PMID- 29214154
TI  - The Search for Biomarkers in Hereditary Angioedema.
AB  - The unpredictable nature of attacks of tissue swelling in hereditary angioedema
      requires the identification of reliable biomarkers to monitor disease activity as
      well as response to therapy. At present, one can assess a C4 level (by ELISA) to
      assist in diagnosis but neither C4 nor C1 inhibitor levels reflect clinical
      course or prognosis. We will here review a collection of plasma proteins involved
      in blood coagulation, fibrinolysis, and innate immunity (Figure 1). A main focus
      is those proteins that are key to the formation of bradykinin (BK); namely,
      factor XII, plasma prekallikrein/kallikrein, high-molecular weight kininogen, and
      BK itself since overproduction of BK is key to the disease. Considerations
      include new approaches to measurement of active enzymes, ELISA methods that may
      supersede SDS gel analysis of bond cleavages, and examples of changes outside the
      BK cascade that may reflect when, where, and how an attack of swelling is
      initiated. We will discuss their usefulness as biomarker candidates, with pros
      and cons, and compare the analytical methods that are being developed to measure
      their levels or activity.

PMID- 29214155
TI  - A Pilot Randomized Controlled Trial of a Technology-Based Approach for Preventing
      Excess Weight Gain during Pregnancy among Women with Overweight.
AB  - Objective: Overweight/obesity and excess weight gain during pregnancy are
      associated with adverse maternal and neonatal outcomes. Few interventions have
      been effective in limiting gestational weight gain among women with overweight or
      obesity. This pilot, randomized clinical trial compared treatment as usual (TAU)
      to a lifestyle modification program delivered via phone for the prevention of
      excess gestational weight gain in women who had overweight or obesity. Methods:
      Participants included 41 pregnant women with a body mass index (BMI) >= 25 kg/m2
      (mean age = 28.7 +/- 5.8 years; mean pre-gravid BMI = 31.2 +/- 6.2 kg/m2; 54%
      black, 39% white). The intervention group (n = 20) received weekly telephone
      counseling sessions and used WiFi scales to monitor their weight from weeks 16 to
      36 of pregnancy. We compared differences in weight and birth outcomes for the
      intervention vs. the TAU group (n = 21). Results: The intervention and TAU groups
      did not differ with respect to: gestational weight gain (15.5 +/- 5.3 vs. 13.3 +/
      6.8 kg, respectively); proportion gaining above the 2009 Institute of Medicine
      recommended weight range (83 vs. 70%); and weight gain from pre-pregnancy weight
      to 6 weeks postpartum (4.8 +/- 4.6 vs. 3.0 +/- 5.5 kg). Other birth and health
      outcomes also did not differ. Conclusion: A telemedicine intervention designed to
      decrease logistical burden on participants was not more successful in reducing
      excessive weight gain during pregnancy as compared to TAU. Future studies should
      examine more intensive forms of remote treatment beginning earlier in pregnancy
      as well as interventions promoting a healthy weight prior to pregnancy.

PMID- 29214156
TI  - Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to
      treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency
      syndrome. Development of severe mitochondrial toxicity has been well documented
      in patients infected with HIV and administered NRTIs. In vitro biochemical
      experiments have demonstrated that the replicative mitochondrial DNA (mtDNA)
      polymerase gamma, Polg, is a sensitive target for inhibition by metabolically
      active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs). Once
      incorporated into newly synthesized daughter strands NtRTIs block further DNA
      polymerization reactions. Human cell culture and animal studies have demonstrated
      that cell lines and mice exposed to NRTIs display mtDNA depletion. Further
      complicating NRTI off-target effects on mtDNA maintenance, two additional DNA
      polymerases, Pol beta and PrimPol, were recently reported to localize to
      mitochondria as well as the nucleus. Similar to Polg, in vitro work has
      demonstrated both Pol beta and PrimPol incorporate NtRTIs into nascent DNA. Cell
      culture and biochemical experiments have also demonstrated that antiviral
      ribonucleoside drugs developed to treat hepatitis C infection act as off-target
      substrates for POLRMT, the mitochondrial RNA polymerase and primase. Accompanying
      the above-mentioned topics, this review examines: (1) mtDNA maintenance in human
      health and disease, (2) reports of DNA polymerases theta and zeta (Rev3)
      localizing to mitochondria, and (3) additional drugs with off-target effects on
      mitochondrial function. Lastly, mtDNA damage may induce cell death; therefore,
      the possibility of utilizing compounds that disrupt mtDNA maintenance to kill
      cancer cells is discussed.

PMID- 29214157
TI  - Towards a global initiative for fibrosis treatment (GIFT).
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterised
      by increased scarring of lung tissue. Despite the recent introduction of novel
      drugs that slow disease progression, IPF remains a deadly disease, and the
      benefits of these new drugs differ markedly between patients. Human diseases
      arise due to alterations in an almost limitless network of interconnected genes,
      proteins, metabolites, cells and tissues, in direct relationship with a
      continuously changing macro- or microenvironment. Systems biology is a novel
      research strategy that seeks to understand the structure and behaviour of the so
      called "emergent properties" of complex systems, such as those involved in
      disease pathogenesis, which are most often overlooked when just one element of
      disease pathogenesis is observed in isolation. This article summarises the debate
      that took place during a European Respiratory Society research seminar in
      Barcelona, Spain on December 15-16, 2016, which focused on how systems biology
      could generate new data by integrating the different IPF pathogenic levels of
      complexity. The main conclusion of the seminar was to create a global initiative
      to improve IPF outcomes by integrating cutting-edge international research that
      leverages systems biology to develop a precision medicine approach to tackle this
      devastating disease.

PMID- 29214158
TI  - Optical Coherence Tomography: Basic Concepts and Applications in Neuroscience
      Research.
AB  - Optical coherence tomography is a micrometer-scale imaging modality that permits
      label-free, cross-sectional imaging of biological tissue microstructure using
      tissue backscattering properties. After its invention in the 1990s, OCT is now
      being widely used in several branches of neuroscience as well as other fields of
      biomedical science. This review study reports an overview of OCT's applications
      in several branches or subbranches of neuroscience such as neuroimaging,
      neurology, neurosurgery, neuropathology, and neuroembryology. This study has
      briefly summarized the recent applications of OCT in neuroscience research,
      including a comparison, and provides a discussion of the remaining challenges and
      opportunities in addition to future directions. The chief aim of the review study
      is to draw the attention of a broad neuroscience community in order to maximize
      the applications of OCT in other branches of neuroscience too, and the study may
      also serve as a benchmark for future OCT-based neuroscience research. Despite
      some limitations, OCT proves to be a useful imaging tool in both basic and
      clinical neuroscience research.

PMID- 29214159
TI  - Quality of Care during Neonatal Resuscitation in Kakamega County General
      Hospital, Kenya: A Direct Observation Study.
AB  - Background: Birth asphyxia is the leading cause of neonatal mortality in Kenya.
      Quality care during neonatal resuscitation (NR) can contribute to a reduction in
      neonatal mortality related to birth asphyxia by 30 percent. This study assessed
      the quality of care (QoC) during NR for newborns with birth asphyxia. Methods:
      Direct observations of 138 newborn resuscitations were done in labor ward and
      maternity theatre. Twenty-eight healthcare providers were observed 3-5 times
      using a structured checklist. Descriptive and inferential statistics were
      calculated and quality of care scores computed. Ordered logistic regression model
      identified HCPs characteristics associated with the QoC scores during NR.
      Results: Overall QoC scores were good for airway clearance (83%). Suctioning in
      meconium presence (40%) was poorly performed. Years of experience working in
      maternity were associated with good drying/stimulation (beta = 1.86, P = 0.003,
      CI = 0.626-3.093) and airway maintenance (beta = 1.887, P = 0.009, CI = 0.469
      3.305); nurses were poor compared to doctors during initial bag and mask
      ventilation (beta = -2.338, P = 0.05, CI = -4.732-0.056). Conclusion: Key steps
      in NR are poorly performed during drying and warmth, airway maintenance in
      meconium presence, and ventilation. Mentorship with periodic refresher training
      can improve the care provided during NR.

PMID- 29214160
TI  - miR-217 Is a Useful Diagnostic Biomarker and Regulates Human Podocyte Cells
      Apoptosis via Targeting TNFSF11 in Membranous Nephropathy.
AB  - Background: MicroRNAs have recently been verified as useful diagnostic biomarkers
      in various diseases. In this study, we investigated whether miR-217 is a useful
      diagnostic biomarker and the possible pathological mechanism of miR-217 in this
      disease. Methods: Patients with focal segmental glomerulosclerosis (FSGS),
      membranous nephropathy (MN), and diabetic nephropathy (DN) and control patients
      were enrolled in this study. The miR-217 inhibitor and mimics were transfected
      into human podocyte cells to investigate the pathological mechanism of miR-217 in
      this disease. Relevant indicators were detected and tested. Results: Compared
      with control patients, miR-217 was significantly downregulated and TNFSF11 was
      significantly upregulated in MN. Then, miR-217 had obvious separation between
      patients with MN and control patients, with an AUC of 0.941, a cutoff value of
      <750.0 copies/ul, and sensitivity and specificity of 88.9% and 75.9%. In
      addition, the TNFSF11 was confirmed to be the target gene of miR-217. Finally, in
      in vitro experiments, the upregulation of miR-217 could decrease the expression
      of TNFSF11 and not induce human podocyte cells apoptosis; however, the
      downregulation of miR-217 could bring about an opposite change. Conclusions: miR
      217 is a useful diagnostic biomarker and is involved in human podocyte cells
      apoptosis via targeting TNFSF11 in membranous nephropathy.

PMID- 29214161
TI  - Brain Computer Interface Systems for Neurorobotics: Methods and Applications.

PMID- 29214162
TI  - Current Tissue Molecular Markers in Colorectal Cancer: A Literature Review.
AB  - Background: Colorectal cancer (CRC) is one of the most spread neoplasia types all
      around the world, especially in western areas. It evolves from precancerous
      lesions and adenomatous polyps, through successive genetic and epigenetic
      mutations. Numerous risk factors intervene in its development and they are either
      environmental or genetic. Aim of the Review: Alongside common screening
      techniques, such as fecal screening tests, endoscopic evaluation, and CT
      colonography, we have identified the most important and useful biomarkers and we
      have analyzed their role in the diagnosis, prevention, and prognosis of CRC.
      Conclusion: Biomarkers can become an important tool in the diagnostic and
      therapeutic process for CRC. But further studies are needed to identify a
      noninvasive, cost-effective, and highly sensible and specific screening test for
      their detection and to standardize their use in clinical practice.

PMID- 29214163
TI  - Protective Effects of Pyridoxamine Supplementation in the Early Stages of Diet
      Induced Kidney Dysfunction.
AB  - Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative
      effects, has been proposed as supplementary approach in patients with initial
      diabetic nephropathy. However, the molecular mechanism(s) underlying its
      protective role has been so far slightly examined. C57Bl/6J mice were fed with a
      standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks.
      After 3 weeks, two subgroups of SD and HD mice started pyridoxamine
      supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed
      increased body weight and impaired glucose tolerance, whereas pyridoxamine
      administration significantly improved insulin sensitivity, but not body weight,
      and reduced diet-induced increase in serum creatinine and urine albumin. Kidney
      morphology of HD fed mice showed strong vacuolar degeneration and loss of tubule
      brush border, associated with a drastic increase in both advanced glycation end
      products (AGEs) and AGEs receptor (RAGE). These effects were significantly
      counteracted by pyridoxamine, with consequent reduction of the diet-induced
      overactivation of NF-kB and Rho/ROCK pathways. Overall, the present study
      demonstrates for the first time that the administration of the antiglycative
      compound pyridoxamine can reduce the early stages of diet-dependent kidney injury
      and dysfunction by interfering at many levels with the profibrotic signaling and
      inflammatory cascades.

PMID- 29214164
TI  - Outcome of Critically Ill Patients with Testicular Cancer.
AB  - Purpose: To evaluate the clinical characteristics and outcomes of critically ill
      patients with testicular cancer (TC) admitted to an oncological intensive care
      unit (ICU). Methods: This was a prospective observational study. There were no
      interventions. Results: During the study period, 1,402 patients with TC were
      admitted to the Department of Oncology, and 60 patients (4.3%) were admitted to
      the ICU. The most common histologic type was nonseminomatous germ cell tumors
      (55/91.7%). The ICU, hospital, and 6-month mortality rates were 38.3%, 45%, and
      63.3%, respectively. The Cox multivariate analysis identified the white blood
      cells count (HR = 1.06, 95% CI = 1.01-1.11, and P = 0.005), ionized calcium (iCa)
      level (HR = 1.23, 95% CI = 1.01-1.50, and P = 0.037), and 2 or more organ
      failures during the first 24 hours after ICU admission (HR = 3.86, 95% CI = 1.96
      7.59, and P < 0.001) as independent predictors of death for up to 6 months.
      Conclusion: The ICU, hospital, and 6-month mortality rates were 38.3%, 45%, and
      63.3%, respectively. The factors associated with an increased 6-month mortality
      rate were white blood cells count, iCa level, and 2 or more organ failures during
      the first 24 hours after ICU admission.

PMID- 29214165
TI  - Safety Assessment and Comparison of Sodium Selenite and Bioselenium Obtained from
      Yeast in Mice.
AB  - Detailed safety assessment of sodium selenite and bioselenium (bio-Se) was
      conducted and the results were compared and discussed for the purpose of
      assessing safety of bio-Se for use in food applications. In this work, acute
      toxicity studies, micronucleus test, and sperm aberration study in mice, 30-day
      feeding test of mice, were conducted to evaluate the toxicity of bio-Se obtained
      from yeast with different fermentation time (transformative time: one month,
      three months, and six months), and the results were compared with that of
      inorganic Se (sodium selenite). LD50 of sodium selenite was calculated to be
      21.17 mg/kg. LD50 of bio-Se obtained from yeast with different fermentation time
      was calculated to be 740.2 mg/kg, 915.3 mg/kg, and 1179.0 mg/kg, respectively. In
      the genotoxicity test, bio-Se did not show cytotoxicity and genotoxicity of mice
      while sodium selenite at all dose groups was significantly different from the
      negative group. In the 30-day subchronic oral toxicity study, sodium selenite may
      slow down the growth of the mice and lead to organic damage to some extent. Bio
      Se had facilitated effect towards the body weight of the mice and had no
      significant effect on the shape and function of the important organs of the mice.

PMID- 29214167
TI  - Comparison of US Strain Elastography and Entero-MRI to Typify the Mesenteric and
      Bowel Wall Changes during Crohn's Disease: A Pilot Study.
AB  - Purpose: To evaluate and compare the mesenteric and bowel wall changes during
      Crohn's disease (CD) on ultrasonography (US) Strain Elastography (SE) and
      Enterography Magnetic Resonance Imaging (E-MRI). Methods: From July 2014 to
      September 2016, 35 patients with ileocolonoscopy diagnosis of CD were
      prospectively examined with E-MRI and in the same time with US and SE. Results: A
      total of 41 affected bowel segments and 35 unaffected bowel segments in 35
      patients were evaluated. US-SE color-scale coding showed a blue color pattern in
      the fibrotic mesentery and bowel wall in 15 patients and a green color pattern in
      the edematous ones in 20 patients. The signal of the bowel wall and mesenteric
      fat was iso/hypointense on T2-weighted sequence in the fibrotic pattern (23/35
      and 12/35 patients) and hyperintense in the edematous pattern (12/35 and 23/35
      patients). Mean ADC values were, respectively, 2,58 +/- 0,33 * 10-3 for the
      fibrotic mesentery and 2,14 +/- 0,28 * 10-3 for edematous one. There was a
      statistical correlation between US-SE color-scale and T2 signal intensity and
      between the US-SE color-scale and ADC maps. Conclusions: US-SE, ADC, and signal
      intensity on T2-weighted sequences on MR prove to be useful tools for the
      evaluation of CD pattern.

PMID- 29214168
TI  - How Well Can Modern Nonhabitual Barefoot Youth Adapt to Barefoot and Minimalist
      Barefoot Technology Shoe Walking, in regard to Gait Symmetry.
AB  - We aim to test how well modern nonhabitual barefoot people can adapt to barefoot
      and Minimalist Bare Foot Technology (MBFT) shoes, in regard to gait symmetry. 28
      healthy university students (22 females/6 males) were recruited to walk on a 10
      meter walkway randomly on barefoot, in MBFT shoes, and in neutral running shoes
      at their comfortable walking speed. Kinetic and kinematic data were collected
      using an 8-camera motion capture system. Data of joint angles, joint forces, and
      joint moments were extracted to compute a consecutive symmetry index. Compared to
      walking in neutral running shoes, walking barefoot led to worse symmetry of the
      following: ankle joint force in sagittal plane, knee joint moment in transverse
      plane, and ankle joint moment in frontal plane, while improving the symmetry of
      joint angle in sagittal plane at ankle joints and global (hip-knee-ankle) level.
      Walking in MBFT shoes had intermediate gait symmetry performance as compared to
      walking barefoot/walking in neutral running shoes. We conclude that modern
      nonhabitual barefoot adults will lose some gait symmetry in joint force/moment if
      they switch to barefoot walking without fitting in; MBFT shoe might be an ideal
      compromise for healthy youth as regards gait symmetry in walking.

PMID- 29214166
TI  - miRNAs: Important Targets for Oral Cancer Pain Research.
AB  - Pain is a symptom shared by an incredible number of diseases. It is also one of
      the primary conditions that prompt individuals to seek medical treatment. Head
      and neck squamous cell carcinoma (HNSCC) corresponds to a heterogeneous disease
      that may arise from many distinct structures of a large, highly complex, and
      intricate region. HNSCC affects a great number of patients worldwide and is
      directly associated with chronic pain, which is especially prominent during the
      advanced stages of oral squamous cell carcinoma (OSCC), an anatomical and
      clinical subtype that corresponds to the great majority oral cancers. Although
      the cellular and molecular bases of oral cancer pain have not been fully
      established yet, the results of recent studies suggest that different epigenetic
      mechanisms may contribute to this process. For instance, there is strong
      scientific evidence that microRNAs (miRNAs), small RNA molecules that do not
      encode proteins, might act by regulating the mechanisms underlying cancer-related
      pain. Among the miRNAs that could possibly interfere in pain-signaling pathways,
      miR-125b, miR-181, and miR-339 emerge as some of the most promising candidates.
      In fact, such molecules apparently contribute to inflammatory pain. Moreover,
      these molecules possibly influence the activity of endogenous pain control
      systems (e.g., opioidergic and serotonergic systems), which could ultimately
      result in peripheral and central sensitization, central nervous system (CNS)
      phenomena innately associated with chronic pain. This review paper focuses on the
      current scientific knowledge regarding the involvement of miRNAs in cancer pain,
      with special attention dedicated to OSCC-related pain.

PMID- 29214169
TI  - Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue
      Withdrawal in Chronic Hepatitis B.
AB  - Aims: Proximal renal tubular dysfunction (PRTD) is an infrequent complication
      after nucleotide analogue therapy. We evaluated the outcomes of PRTD and
      nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB).
      Methods: A longitudinal follow-up study was performed in patients with PRTD after
      nucleotide analogue discontinuation. Serum and urine were collected at baseline
      and every 3 months for one year. The fractional excretion of phosphate (PO4),
      uric acid (UA), and potassium and tubular maximal reabsorption rate of PO4 to
      glomerular filtration rate (TmPO4/GFR) were calculated. Renal losses were defined
      based on the criteria of substance losses. Subclinical PRTD and overt PRTD were
      diagnosed when 2 and >=3 criteria were identified. Results: Eight subclinical and
      eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal,
      there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA,
      protein, and beta2-microglobulin reduced over time. At one year, complete
      reversal of PRTD was seen in 13 patients (81.2%). Improvements in PRTD were seen
      in all but one patient. Conclusion: One year after nucleotide analogue
      withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary
      protein, and beta2-microglobulin indicate that urinary biomarkers may represent
      an early sign of PRTD recovery.

PMID- 29214170
TI  - NLRP1 Overexpression Is Correlated with the Tumorigenesis and Proliferation of
      Human Breast Tumor.
AB  - Recent studies suggest that nucleotide-binding domain leucine-rich repeat protein
      1 (NLRP1) is a pivotal factor in the inflammatory process. However, the role of
      NLRP1 in breast cancer pathogenesis remains unclear. The aim of this study was to
      examine the expression and function of NLRP1 in breast cancer. We found that
      NLRP1 was widely expressed in 83% (60/72) of primary breast cancer tissue. NLRP1
      expression level was higher in primary breast cancer tissue than in adjacent
      noncancerous tissue (p < 0.001) and NLRP1 expression was associated with lymph
      node metastasis (p = 0.003), TNM stage (p = 0.003), and Ki-67 levels (p < 0.001).
      Overexpression of NLRP1 in the breast cancer cell line MCF-7 promotes
      proliferation, migration, invasion, and tumorigenicity in nude mice. Restoration
      of NLRP1 expression resulted in the EMT occurrence that downregulation of
      epithelial marker E-cadherin and upregulation mesenchymal marker vimentin, C-myc,
      MMP-9, and snail. In summary, NLRP1 promotes cell line MCF-7 the proliferation,
      migration, and invasion through inducing EMT.

PMID- 29214171
TI  - Evaluating Swine Injection Technologies as a Workplace Musculoskeletal Injury
      Intervention: A Study Protocol.
AB  - Intensification of modern swine production has led to many new technologies,
      including needleless injectors. Although needleless injectors may increase
      productivity (by reducing injection time) and reduce needlestick injuries, the
      effect on risk for musculoskeletal disorders is not clear. This project will
      compare conventional needles with needleless injectors in terms of cost,
      productivity, injury rates, biomechanical exposures, and worker preference.
      Muscle activity (EMG) and hand/wrist posture will be measured on swine workers
      performing injection tasks with both injection methods. Video recordings during
      the exposure assessments will compare the duration and productivity for each
      injection method using time-and-motion methods. Injury claim data from up to 60
      pig barns will be analyzed for needlestick and musculoskeletal injuries
      before/after needleless injector adoption. Workers and managers will be asked
      about what they like and dislike about each method and what helps and hinders
      successful implementation. The information above will be input into a cost
      benefit model to determine the incremental effects of needleless injectors in
      terms of occupational health, worker preference, and the financial "bottom line"
      of the farm. Findings will be relevant to the swine industry and are intended to
      be transferable to other new technologies in animal production.

PMID- 29214173
TI  - Fabrication and In Vitro Study of Tissue-Engineered Cartilage Scaffold Derived
      from Wharton's Jelly Extracellular Matrix.
AB  - The scaffold is a key element in cartilage tissue engineering. The components of
      Wharton's jelly are similar to those of articular cartilage and it also contains
      some chondrogenic growth factors, such as insulin-like growth factor I and
      transforming growth factor-beta. We fabricated a tissue-engineered cartilage
      scaffold derived from Wharton's jelly extracellular matrix (WJECM) and compared
      it with a scaffold derived from articular cartilage ECM (ACECM) using freeze
      drying. The results demonstrated that both WJECM and ACECM scaffolds possessed
      favorable pore sizes and porosities; moreover, they showed good water uptake
      ratios and compressive moduli. Histological staining confirmed that the WJECM and
      ACECM scaffolds contained similar ECM. Moreover, both scaffolds showed good
      cellular adherence, bioactivity, and biocompatibility. MTT and DNA content
      assessments confirmed that the ACECM scaffold tended to be more beneficial for
      improving cell proliferation than the WJECM scaffold. However, RT-qPCR results
      demonstrated that the WJECM scaffold was more favorable to enhance cellular
      chondrogenesis than the ACECM scaffold, showing more collagen II and aggrecan
      mRNA expression. These results were confirmed indirectly by glycosaminoglycan and
      collagen content assessments and partially confirmed by histology and
      immunofluorescent staining. In conclusion, these results suggest that a WJECM
      scaffold may be favorable for future cartilage tissue engineering.

PMID- 29214174
TI  - Feasibility of Round Window Stimulation by a Novel Electromagnetic Microactuator.
AB  - Introduction: Most implantable hearing aids currently available were developed to
      compensate the sensorineural hearing loss by driving middle ear structures (e.g.,
      the ossicles). These devices are successfully used in round window (RW)
      stimulation clinically, although this was initially not the intended use. Here, a
      novel microactuator, specifically designed for RW stimulation, was tested in
      human temporal bones to determine actuator performance and applicability.
      Methods: Stapes footplate response to RW stimulation was determined
      experimentally in human temporal bones and the obtained sound pressure output
      level was estimated. Results: The actuator had a flat displacement response
      between 0.125 and 4 kHz, a resonance between 4 and 7 kHz, and a roll-off above.
      At increasing contact force, the stapes footplate displacement decreased by 5-10
      dB re MUm for forces >= 2 mN. The equivalent sound pressure level between 0.125
      and 4 kHz amounted to 87-97 eq dB SPL and increased to 117 eq dB SPL for
      frequencies of 4-7 kHz. The total harmonic distortion (THD) of the actuator
      ranged within 15-40% for static forces of 5 mN. Conclusion: The feasibility of an
      electromagnetic actuator that may be placed into the RW niche was demonstrated
      but requires further optimization in terms of THD and static force sensitivity.

PMID- 29214172
TI  - Migraine and Complex Regional Pain Syndrome: A Case-Referent Clinical Study.
AB  - We studied clinical phenotype differences between migraineurs with CRPS (Mig +
      CRPS) and those without (Mig - CRPS). Mig + CRPS cases and Mig - CRPS referents
      aged >=18 years were enrolled. Diagnosis was made in accordance with
      International Classification of Headache Disorders-3 beta (ICHD-3 beta) for
      migraine and Budapest Criteria for CRPS. Migraines both with and without aura
      were included. A total of 70 Mig + CRPS cases (13% males, mean age 48 years) and
      80 Mig - CRPS referents (17% males, mean age 51 years) were included. 33% of Mig
      + CRPS and 38% of Mig - CRPS exhibited episodic migraine (EM) while 66% of Mig +
      CRPS and 62% of Mig - CRPS had chronic migraine (CM) (OR = 0.98, CI 0.36, 2.67).
      Median duration of CRPS was 3 years among EM + CRPS and 6 years among CM + CRPS
      cohort (p < 0.02). Mig + CRPS (57%) carried higher psychological and medical
      comorbidities compared to Mig - CRPS (6%) (OR 16.7, CI 10.2, 23.6). Higher
      migraine frequency was associated with longer CRPS duration. Migraineurs who
      developed CRPS had higher prevalence of psychological and medical disorders.
      Alleviating migraineurs' psychological and medical comorbidities may help lower
      CRPS occurrence.

PMID- 29214175
TI  - What Healthcare Workers Should Know about Environmental Bacterial Contamination
      in the Intensive Care Unit.
AB  - Intensive care unit- (ICU-) acquired infections are a major health problem
      worldwide. Inanimate surfaces and equipment contamination may play a role in
      cross-transmission of pathogens and subsequent patient colonization or infection.
      Bacteria contaminate inanimate surfaces and equipment of the patient zone and
      healthcare area, generating a reservoir of potential pathogens, including
      multidrug resistant species. Traditional terminal cleaning methods have
      limitations. Indeed patients who receive a bed from prior patient carrying
      bacteria are exposed to an increased risk (odds ratio 2.13, 95% confidence
      intervals 1.62-2.81) of being colonized and potentially infected by the same
      bacterial species of the previous patient. Biofilm formation, even on dry
      surfaces, may play a role in reducing the efficacy of terminal cleaning
      procedures since it enables bacteria to survive in the environment for a long
      period and provides increased resistance to commonly used disinfectants. No-touch
      methods (e.g., UV-light, hydrogen peroxide vapour) are under investigation and
      further studies with patient-centred outcomes are needed, before considering them
      the standard of terminal cleaning in ICUs. Healthcare workers should be aware of
      the role of environmental contamination in the ICU and consider it in the broader
      perspective of infection control measures and stewardship initiatives.

PMID- 29214176
TI  - Human Gut Microbiota Associated with Obesity in Chinese Children and Adolescents.
AB  - Objective: To investigate the gut microbiota differences of obese children
      compared with the control healthy cohort to result in further understanding of
      the mechanism of obesity development. Methods: We evaluated the 16S rRNA gene,
      the enterotypes, and quantity of the gut microbiota among obese children and the
      control cohort and learned the differences of the gut microbiota during the
      process of weight reduction in obese children. Results: In the present study, we
      learned that the gut microbiota composition was significantly different between
      obese children and the healthy cohort. Next we found that functional changes,
      including the phosphotransferase system, ATP-binding cassette transporters,
      flagellar assembly, and bacterial chemotaxis were overrepresented, while glycan
      biosynthesis and metabolism were underrepresented in case samples. Moreover, we
      learned that the amount of Bifidobacterium and Lactobacillus increased among the
      obese children during the process of weight reduction. Conclusion: Our results
      might enrich the research between gut microbiota and obesity and further provide
      a clinical basis for therapy for obesity. We recommend that Bifidobacterium and
      Lactobacillus might be used as indicators of healthy conditions among obese
      children, as well as a kind of prebiotic and probiotic supplement in the diet to
      be an auxiliary treatment for obesity.

PMID- 29214177
TI  - Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic
      Web Layer.
AB  - Patient registries are an essential tool to increase current knowledge regarding
      rare diseases. Understanding these data is a vital step to improve patient
      treatments and to create the most adequate tools for personalized medicine.
      However, the growing number of disease-specific patient registries brings also
      new technical challenges. Usually, these systems are developed as closed data
      silos, with independent formats and models, lacking comprehensive mechanisms to
      enable data sharing. To tackle these challenges, we developed a Semantic Web
      based solution that allows connecting distributed and heterogeneous registries,
      enabling the federation of knowledge between multiple independent environments.
      This semantic layer creates a holistic view over a set of anonymised registries,
      supporting semantic data representation, integrated access, and querying. The
      implemented system gave us the opportunity to answer challenging questions across
      disperse rare disease patient registries. The interconnection between those
      registries using Semantic Web technologies benefits our final solution in a way
      that we can query single or multiple instances according to our needs. The
      outcome is a unique semantic layer, connecting miscellaneous registries and
      delivering a lightweight holistic perspective over the wealth of knowledge
      stemming from linked rare disease patient registries.

PMID- 29214178
TI  - Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle
      Atrophy.
AB  - Muscle biopsy has long been expected to be replaced by noninvasive biomarkers
      with diagnostic value and prognostic applications for muscle atrophy. Growing
      evidence suggests that circulating microRNAs (miRNAs) could act as biomarkers for
      numerous pathophysiological statuses. In the present study, our results showed
      that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499)
      were all elevated in unloading induced mice. The medium levels of these six
      muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12
      myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in
      participants after 45 days of head-down bed rest (HDBR). The levels of miR
      23a/206/499 were positively correlated with the ratio of soleus volume loss in
      HDBR participants, indicating that they might represent the process of muscle
      loss. In conclusion, our results demonstrated that circulating miRNAs could serve
      as useful biochemical and molecular indicators for muscle atrophy diagnosis and
      disease progression.

PMID- 29214179
TI  - The Roles of Thrombospondins in Hemorrhagic Stroke.
AB  - Hemorrhagic stroke is a devastating cerebrovascular disease with significant
      morbidity and mortality worldwide. Thrombospondins (TSPs), as matricellular
      proteins, belong to the TSP family which is comprised of five members. All TSPs
      modulate a variety of cellular functions by binding to various receptors.
      Recently, TSPs gained attention in the area of hemorrhagic stroke, especially TSP
      1. TSP-1 participates in angiogenesis, the inflammatory response, apoptosis, and
      fibrosis after hemorrhagic stroke through binding to various molecules including
      but not limited to CD36, CD47, and TGF-beta. In this review, we will discuss the
      roles of TSPs in hemorrhagic stroke and focus primarily on TSP-1.

PMID- 29214180
TI  - Circulating MicroRNA Profiles Differ between Hyperglycemia and Euglycemia in
      Coronary Heart Disease Patients.
AB  - Coronary heart disease (CHD) has become one of the leading causes of death and
      functional impairment in the world. Hyperglycemia is associated with an increased
      risk of cardiovascular disease. It was speculated that miRNAs in peripheral blood
      were a primary parameter in discriminating CHD. The biological characteristics of
      coronary heart disease with hyperglycemia (HCHD) and coronary heart disease with
      euglycemia (ECHD) were investigated in the study. Circulating miRNAs from 26 HCHD
      patients and 42 ECHD patients were identified by microarrays. Compared with the
      healthy patients, 15 and 20 differentially expressed miRNAs were identified in
      HCHD and ECHD groups, respectively. Gene ontology analysis was carried out by
      DAVID and functional annotations of the miRNA targets related to ATP binding,
      cellular components, protein binding, RNA binding, DNA binding, and so on. KEGG
      database was used for pathway analysis. Eleven pathways were identified in both
      HCHD and ECHD groups. Furthermore, 13 and 3 pathways were only identified in HCHD
      or ECHD group, respectively. And then, miRNA-gene regulatory networks were
      constructed to study the relationship between differentially expressed miRNAs and
      genes. This suggested that hsa-let-7c-5p and hsa-miR-24-3p might have the most
      important function for hyperglycemia in coronary heart disease patients.

PMID- 29214181
TI  - Cardiac Autonomic Neuropathy: Why Should Cardiologists Care about That?
AB  - Background: Cardiac autonomic neuropathy (CAN) is a frequent but underdiagnosed
      complication of diabetes mellitus. It has a strong influence on various cardiac
      disorders including myocardial ischemia and infarction, hypertension, orthostatic
      hypotonia, heart failure, and arrhythmias. CAN can lead to severe morbidity and
      mortality and increase the risk of sudden cardiac death. Methods: This review
      article summarizes the latest evidence regarding the epidemiology, pathogenesis,
      influence on the cardiovascular system, and diagnostic methods for CAN. The
      methodology of this review involved analyzing available data from recent papers
      relevant to the topic of diabetic autonomic neuropathy and cardiac disorders.
      Conclusions: The early diagnosis of CAN can improve the prognosis and reduce
      adverse cardiac events. Methods based on heart rate variability enable the
      diagnosis of CAN even at a preclinical stage. These methods are simple and widely
      available for use in everyday clinical practice. According to the recently
      published Toronto Consensus Panel on Diabetic Neuropathy, all diabetic patients
      should be screened for CAN. Because diabetes mellitus often coexists with heart
      diseases and the most common methods used for diagnosis of CAN are based on ECG,
      not only diabetologists but also cardiologists should be responsible for
      diagnosis of CAN.

PMID- 29214182
TI  - Thyroid Dysfunction among Greek Patients with Type 1 and Type 2 Diabetes Mellitus
      as a Disregarded Comorbidity.
AB  - Introduction: The aim of this study was to determine the prevalence of thyroid
      dysfunction in Greek patients with type 1 (T1DM) and type 2 (T2DM) diabetes
      mellitus as well as its possible relations to glycaemic control and to diabetic
      complications. Methods: A total of 1015 patients, consecutively followed in the
      Outpatient Diabetes Center, were studied. Anthropometric and biochemical
      measurements, occurrence of diabetes complications, and classical comorbidities
      were assessed. Average HbA1c of the previous year was calculated. Wellbeing was
      determined, using a 10-point optimal scale. All the above parameters were
      compared between subjects with or without thyroid disease. Results: All patients
      were euthyroid at the time of the study, either on thyroid medications or not.
      Hypothyroidism occurrence did not differ between T2DM and T1DM patients (37.1%
      versus 43.5%, p > 0.05). Nodular goiter was observed more frequently in T2DM
      patients (34.1% versus 18.8%, p < 0.05). T2DM patients with hypothyroidism
      compared to those without hypothyroidism had higher HbA1c (7.27% versus 6.98%, p
      < 0.01), TChol (184.97 mg/dl versus 168.17 mg/dl, p < 0.001), and higher HDL-Chol
      (51.28 mg/dl versus 46.77 mg/dl, p < 0.01). T2DM patients without hypothyroidism
      had a better wellness feeling (7.5 versus 5.3 points, p < 0.01). Conclusions:
      Screening for thyroid disease among T2DM patients should be routinely considered,
      as it is found to be an additional commorbidity. If it remains undiagnosed, it
      could aggravate the clinical course of the disease.

PMID- 29214183
TI  - Direct and Indirect Effects of Serum Uric Acid on Blood Sugar Levels in Patients
      with Prediabetes: A Mediation Analysis.
AB  - Purpose: To estimate both direct and indirect effects (through obesity) of serum
      uric acid (SUA) on blood sugar in prediabetes patients. Methods: Prediabetes
      patients who came to the outpatient clinic of the Department of Family Medicine,
      Ramathibodi Hospital, were included in this cross-sectional study. Mediation
      analysis was applied to determine direct and indirect effects of SUA on glycemic
      parameters (fasting plasma glucose (FPG) and HbA1c) through waist circumference
      (WC). A mediation effect was estimated using the product-of-coefficient method
      with a bootstrap analysis of 1000 replications. Results: 1043 patients were
      eligible for this study. Every 1 mg/dl increase in SUA was associated with an
      increase in WC and then was significantly associated with an increase in FPG by
      0.082 mg/dl (95% CI: 0.010, 0.154). SUA was directly associated with FPG with a
      coefficient of 0.413 (95% CI: 0.049, 0.776). For HbA1c, every one mg/dl increase
      in SUA was associated with an increase in HbA1c level through WC by 0.006 (95%
      CI: 0.003, 0.010). However, SUA was not directly associated with HbA1c.
      Conclusions: We found that an increase in SUA was directly and indirectly
      associated with increased FPG but the effect of SUA on HbA1c was shown when it
      was mediated through WC.

PMID- 29214184
TI  - Protective Effects of Moringa oleifera on HBV Genotypes C and H Transiently
      Transfected Huh7 Cells.
AB  - Chronic hepatitis B infection treatment implicates a long-lasting treatment. M.
      oleifera extracts contain compounds with antiviral, antioxidant, and antifibrotic
      properties. In this study, the effect of M. oleifera was evaluated in Huh7 cells
      expressing either HBV genotypes C or H for the antiviral, antifibrotic, anti
      inflammatory, and antioxidative responses. Huh7 cells were treated with an
      aqueous extract of M. oleifera (leaves) at doses of 0, 30, 45, or 60 MUg/mL. The
      replicative virus and TGF-beta1, CTGF, CAT, IFN-beta1, and pgRNA expressions were
      measured by real time. HBsAg and IL-6 titers were determined by ELISA. CTGF, TGF
      beta1, IFN-beta1, and pgRNA expressions decreased with M. oleifera treatment
      irrespective of the HBV genotype. HBsAg secretion in the supernatant of
      transfected Huh7 cells with both HBV genotypes was decreased regardless of the
      dose of M. oleifera. Similar effect was observed in proinflammatory cytokine IL
      6, which had a tendency to decrease at 24 hours of treatment. Transfection with
      both HBV genotypes strongly decreased CAT expression, which is retrieved with M.
      oleifera treatment. M. oleifera treatment reduced fibrosis markers, IL-6, and
      HBsAg secretion in HBV genotypes C and H. However, at the level of replication,
      only HBV-DNA genotype C was slightly reduced with this treatment.

PMID- 29214186
TI  - A rare case of failed healing in previously burned skin after a secondary burns.
AB  - Background: Patients presenting with large surface area burns are common in our
      practice; however, patients with a secondary large burn on pre-existing burn
      scars and grafts are rare and not reported. Case presentation: We report on an
      unusual case of a patient sustaining a secondary large burn to areas previously
      injured by a burn from a different mechanism. We discuss the potential
      implications when managing a case like this and suggest potential biological
      reasons why the skin may behave differently. Our patient was a 33-year-old man
      who presented with a 5% TBSA burn on skin scarred by a previous 40% total body
      surface area (TBSA) burn and skin grafts. Initially assessed as superficial
      partial thickness in depth, the wounds were treated conservatively with
      dressings; however, they failed to heal and became infected requiring surgical
      management. Conclusions: Burns sustained in areas of previous burn scars and
      grafts may behave differently to normal patterns of healing, requiring more
      aggressive management and surgical intervention at an early stage.

PMID- 29214185
TI  - Administration of Rhodiola kirilowii Extracts during Mouse Pregnancy and
      Lactation Stimulates Innate but Not Adaptive Immunity of the Offspring.
AB  - The use of antibiotics during pregnancy and lactation is associated with an
      increased risk of developmental disorders. One of the natural medicinal plants
      Rhodiola kirilowii, widely used as an immunostimulant in adults-might be a good
      alternative to antibiotic treatment. The aim of present study was to assess
      whether daily oral administration of 20 mg/kg of Rhodiola kirilowii aqueous (RKW)
      or 50% hydroalcoholic (RKW-A) extracts affected hematological and immunological
      parameters of 6-week-old mouse progeny. There was no significant change in
      hematological parameters of blood with the exception of hemoglobin, which was
      significantly higher (about 4%) in RKW group. Offspring of mothers fed Rhodiola
      kirilowii extracts had increased percentage of granulocytes and decreased
      percentage of lymphocytes. These changes correlated with decreased percentage of
      CD3+/CD4+ T-cells (RKW and RKW-A), decrease of CD8+ cells, and increase
      percentage of NK cells in RKW group. In addition, both types of Rhodiola
      kirilowii extracts stimulated granulocyte phagocytosis and increased level of
      respiratory burst. In conclusion, the long-term supplementation of mouse mothers
      during pregnancy and lactation with RKW or RKW-A extracts affects the immune
      system of their progeny. These results should be taken into consideration before
      administration of Rhodiola kirilowii to pregnant and lactating women.

PMID- 29214187
TI  - High-power femtosecond pulses without a modelocked laser.
AB  - We demonstrate a fiber system which amplifies and compresses pulses from a gain
      switched diode. A Mamyshev regenerator shortens the pulses and improves their
      coherence, enabling subsequent amplification by parabolic pre-shaping. As a
      result, we are able to control nonlinear effects and generate nearly transform
      limited, 140-fs pulses with 13-MW peak power-an order-of-magnitude improvement
      over previous gain-switched diode sources. Seeding with a gain-switched diode
      results in random fluctuations of 2% in the pulse energy, which future work using
      known techniques may ameliorate. Further development may allow such systems to
      compete directly with sources based on modelocked oscillators in some
      applications while enjoying unparalleled robustness and repetition rate control.

PMID- 29214189
TI  - Data on flow cell optimization for membrane-based electrokinetic energy
      conversion.
AB  - This article elaborates on the design and optimization of a specialized flow cell
      for the measurement of direct conversion of pressure into electrical energy
      (Electrokinetic Energy Conversion, EKEC) which has been presented in Ostedgaard
      Munck et al. (2017) [1]. Two main flow cell parameters have been monitored and
      optimized: A) the hydraulic pressure profile on each side of the membrane
      introduced by pumps recirculating the electrolyte solution through the flow
      fields and B) the electrical resistance between the current collectors across the
      combined flow cell. The latter parameter has been measured using four-point
      Electrochemical Impedance spectroscopy (EIS) for different flow rates and
      concentrations. The total cell resistance consists of contributions from
      different components: the membrane [Formula: see text], anode charge transfer
      [Formula: see text], cathode charge transfer [Formula: see text], and ion
      diffusion in the porous electrodes [Formula: see text]. The intrinsic membrane
      properties of Nafion 117 has been investigated experimentally in LiI/I2 solutions
      with concentrations ranging between 0.06 and 0.96 M and used to identify the
      preferred LiI/I2 solution concentration. This was achieved by measuring the
      solution uptake, internal solution concentration and ion exchange capacity. The
      membrane properties were further used to calculate the transport coefficients and
      electrokinetic Figure of merit in terms of the Uniform potential and Space charge
      models. Special attention has been put on the streaming potential coefficient
      which is an intrinsic property.

PMID- 29214190
TI  - Dataset on the regulation of banana weevil abundance and corm damage associated
      with plant richness and the ground-dwelling arthropods' food web.
AB  - The data presented in this article are related to the research article entitled
      "Plant richness enhances banana weevil regulation in a tropical agroecosystem by
      affecting a multitrophic food web " [1]. It provides information about plant
      species richness, weevil corm damage and the abundance of different arthropod
      groups, including the banana weevil and its potential natural enemies and
      alternative preys.

PMID- 29214188
TI  - The effects of acute stress on the calibration of persistence.
AB  - People frequently fail to wait for delayed rewards after choosing them. These
      preference reversals are sometimes thought to reflect self-control failure. Other
      times, however, continuing to wait for a delayed reward may be counterproductive
      (e.g., when reward timing uncertainty is high). Research has demonstrated that
      people can calibrate how long to wait for rewards in a given environment. Thus,
      the role of self-control might be to integrate information about the environment
      to flexibly adapt behavior, not merely to promote waiting. Here we tested effects
      of acute stress, which has been shown to tax control processes, on persistence,
      and the calibration of persistence, in young adult human participants. Half the
      participants (n = 60) performed a task in which persistence was optimal, and the
      other half (n = 60) performed a task in which it was optimal to quit waiting for
      reward soon after each trial began. Each participant completed the task either
      after cold pressor stress or no stress. Stress did not influence persistence or
      optimal calibration of persistence. Nevertheless, an exploratory analysis
      revealed an "inverted-U" relationship between cortisol increase and performance
      in the stress groups, suggesting that choosing the adaptive waiting policy may be
      facilitated with some stress and impaired with severe stress.

PMID- 29214191
TI  - Vascular mechanotransduction data in a rodent model of diabetes: Pressure-induced
      regulation of SHP2 and associated signaling in the rat inferior vena cava.
AB  - The effect of diabetes on vascular mechano-transductive response is of great
      concern. Given the higher rate of vein graft failures associated with diabetes,
      understanding the multiple cellular and molecular events associated with vascular
      remodeling is of vital importance. This article represents data related to a
      study published in Cardiovascular Diabetology [1] (Rice et al., 2006) and Open
      Journal of Endocrine and Metabolic Diseases [2] (Rice et al., 2015) evaluating
      the effect of pressurization on rat inferior venae cavae (IVC). Provided within
      this articles is information related to the method and processing of raw data
      related to our prior publish work and Data in Brief articles [3], [4] (Rice et
      al., 2017), as well as the evaluation of alternation in SHP-2 signaling and
      associated proteins in response to mechanical force. IVC from lean and obese
      animals were exposed to a 30 min perfusion of 120 mm Hg pressure and evaluated
      for changes in expression of SHP2, BCL-3, BCL-XL, HSP 27, HSP 70, and PI3K p85,
      along with the phosphorylation of SHP-2 (Tyr 542).

PMID- 29214192
TI  - EEG/EOG/EMG data from a cross sectional study on psychophysiological insomnia and
      normal sleep subjects.
AB  - The data presented here had been originally collected for a research project
      entitled 'Sleep EEG spectral analysis in psychophysiological insomnia and normal
      sleep subjects'. This article describes the data of 11 subjects, referred to
      Sleep Disorders Research Center (SDRC) in Kermanshah, Iran. The data includes 14
      EEG, 6 EOG, and 3 EMG channels, with a sampling ratio of 256 Hz. It includes
      power spectral features in segments of 30 s for each channel, and nonlinear
      analysis parameter. Also, the complete demographic and polysomnography
      specifications are attached.

PMID- 29214193
TI  - Transcriptomic data of Arabidopsis hypocotyl overexpressing a heterologous
      CsEXPA1 gene.
AB  - Expansin increases cell wall extensibility to allow cell wall loosening and cell
      expansion even in the absence of hydrolytic activity. Previous studies showed
      that excessive overexpression of expansin gene resulted in defective growth (Goh
      et al., 2014; Rochange et al., 2001) [1,2] and altered cell wall chemical
      composition (Zenoni et al., 2011) [3]. However, the molecular mechanism on how
      the overexpression of non-enzymatic cell wall protein expansin can result in
      widespread effects on plant cell wall and organ growth remains unclear. We
      acquired transcriptomic data on previously reported transgenic Arabidopsis line
      (Goh et al., 2014) [1] to investigate the effects of overexpressing a heterologus
      cucumber expansin gene (CsEXPA1) on the global gene expression pattern during
      early and late phases of etiolated hypocotyl growth.

PMID- 29214194
TI  - Data concerning the effect of plyometric training on jump performance in soccer
      players: A meta-analysis.
AB  - Plyometric training (PT) enhances soccer performance, particularly vertical jump.
      However, the effectiveness of PT depends on various factors. A systematic search
      of the research literature was conducted for randomized controlled trials (RCTs)
      studying the effects of PT on countermovement jump (CMJ) height in soccer
      players. Ten studies were obtained through manual and electronic journal searches
      (up to April 2017). Significant differences were observed when compared: (1) PT
      group vs. control group (ES=0.85; 95% CI 0.47-1.23; I2=68.71%; p<0.001), (2) male
      vs. female soccer players (Q=4.52; p=0.033), (3) amateur vs. high-level players
      (Q=6.56; p=0.010), (4) single session volume (<120 jumps vs. >=120 jumps; Q=6.12,
      p=0.013), (5) rest between repetitions (5 s vs. 10 s vs. 15 s vs. 30 s; Q=19.10,
      p<0.001), (6) rest between sets (30 s vs. 60 s vs. 90 s vs. 120 s vs. 240 s;
      Q=19.83, p=0.001) and (7) and overall training volume (low: <1600 jumps vs. high:
      >=1600 jumps; Q=5.08, p=0.024). PT is an effective form of training to improve
      vertical jump performance (i.e., CMJ) in soccer players. The benefits of PT on
      CMJ performance are greater for interventions of longer rest interval between
      repetitions (30 s) and sets (240 s) with higher volume of more than 120 jumps per
      session and 1600 jumps in total. Gender and competitive level differences should
      be considered when planning PT programs in soccer players.

PMID- 29214195
TI  - Work stress, fatigue and risk behaviors at the wheel: Data to assess the
      association between psychosocial work factors and risky driving on Bus Rapid
      Transit drivers.
AB  - This Data in Brief (DiB) article presents a hierarchical multiple linear
      regression model that examine the associations between psychosocial work factors
      and risk behaviors at the wheel in Bus Rapid Transit (BRT) drivers (n=524). The
      data were collected using a structured self-administrable questionnaire made of
      measurements of wok stress (job strain and effort- reward imbalance), fatigue
      (need for recovery and chronic fatigue), psychological distress and demographics
      (professional driving experience, hours driven per day and days working per
      week). The data contains 4 parts: descriptive statistics, bivariate correlations
      between the study variables and a regression model predicting risk behaviors at
      the wheel and the entire study dataset. For further information, it is convenient
      to read the full article entitled "Stress-related Psychosocial Factors at Work,
      Fatigue, and Risky Driving Behavior in Bus Rapid Transport (BRT) Drivers",
      published in Accident Analysis & Prevention.

PMID- 29214196
TI  - Structural and biochemical data of Trichoderma harzianum GH1 beta-glucosidases.
AB  - Here the statistics concerning X-ray data processing and structure refinement are
      given, together with the substrate preference analysis for ThBgl1 and ThBgl2.
      Finally, the analysis of the influence of temperature and pH on the activities of
      both enzymes are shown.

PMID- 29214197
TI  - Genotoxicity assessment data for exfoliated buccal cells exposed to mobile phone
      radiation.
AB  - Healthy mobile phone users aged 18-30 y.o. provided exfoliated buccal cells
      samples from the right and left inner cheeks. A total of 2000 cells per subject
      were screened for the presence of micronuclei as a sign of genotoxic damage,
      according to the mobile phone use profile of each user.

PMID- 29214198
TI  - Data on introduced plants in Zimbabwe: Floristic changes and patterns of
      collection based on historical herbarium records.
AB  - National herbaria with significant historical plant collections are critical to
      tracking floristic changes and patterns, which include the introduction and
      spread of non-native plant species. To explore the importance of herbarium
      specimen data in understanding floristic changes in Zimbabwe, the plant
      collections housed by the National Herbarium (SRGH) in Harare, Zimbabwe were
      utilized with historical specimens dating back to 1870. A list of naturalised
      plant taxa and collection data were compiled. A total of 2916 plant specimens
      were recorded, comprising of 401 taxa, 237 genera and 76 plant families. Twenty
      eight specimens (1.0%) were collected between 1870 and 1908, prior to the
      establishment of the National Herbarium in 1909 and 123 specimens (4.2%) were
      collected in the first 25 years of the establishment of the institute (1909
      1934). Intensive collection of herbarium specimens of casual, naturalised and
      invasive alien plant species occurred between 1950 and 1970. This data
      demonstrates the utility of plant species data housed in the National Herbaria
      and how such data can be used to map floristic changes and patterns.

PMID- 29214199
TI  - Dataset of Near-infrared spectroscopy measurement for amylose determination using
      PLS algorithms.
AB  - In the dataset presented in this article, 168 rice samples comprising sixteen
      rice varieties (including Indica and Japonica sub species) from a Portuguese Rice
      Breeding Program obtained from three different sites along four seasons, and 11
      standard rice varieties from International Rice Research Institute were
      characterised. The amylose concentration was evaluated based on iodine method,
      and the near infrared (NIR) spectra were determined. To assess the advantage of
      Near infrared spectroscopy, different rice varieties and specific algorithms
      based on Matlab software such as Standard Normal Variate (SNV), Multiple Scatter
      Calibration (MSC) and Savitzky-Golay filter were used for NIR spectra pre
      processing.

PMID- 29214200
TI  - Data on the sensory evaluation of potatoes (Solanum tuberosum) from different
      areas of Hokkaido, Japan, performed by untrained young adults.
AB  - This data article describes a sensory evaluation of potatoes used in food
      processing from the Tokachi, Kamikawa, and Abashiri geographic areas of Hokkaido,
      Japan, performed by untrained young adults. We gathered sensory data on potatoes
      from the four cultivars 'Toyoshiro,' 'Kitahime,' 'Snowden,' and 'Poroshiri.' The
      sensory evaluation was performed on steamed potatoes from each cultivar; these
      potatoes were harvested from each of the three geographic areas. Table 1 provides
      the data from the evaluation of the five basic tastes (sweet, salty, sour,
      bitter, and umami), as well as the evaluation of the egumi taste, which is a
      Japanese term indicating a taste that is acrid, astringent, and slightly bitter.

PMID- 29214201
TI  - Genotyping-by-sequencing data of 272 crested wheatgrass (Agropyron cristatum)
      genotypes.
AB  - Crested wheatgrass [Agropyron cristatum L. (Gaertn.)] is an important cool-season
      forage grass widely used for early spring grazing. However, the genomic resources
      for this non-model plant are still lacking. Our goal was to generate the first
      set of next generation sequencing data using the genotyping-by-sequencing
      technique. A total of 272 crested wheatgrass plants representing seven breeding
      lines, five cultivars and five geographically diverse accessions were sequenced
      with an Illumina MiSeq instrument. These sequence datasets were processed using
      different bioinformatics tools to generate contigs for diploid and tetraploid
      plants and SNPs for diploid plants. Together, these genomic resources form a
      fundamental basis for genomic studies of crested wheatgrass and other wheatgrass
      species. The raw reads were deposited into Sequence Read Archive (SRA) database
      under NCBI accession SRP115373 (https://www.ncbi.nlm.nih.gov/sra?term=SRP115373)
      and the supplementary datasets are accessible in Figshare
      (10.6084/m9.figshare.5345092).

PMID- 29214202
TI  - Dataset for Phase I randomized clinical trial for safety and tolerability of GET
      73 in single and repeated ascending doses including preliminary pharmacokinetic
      parameters.
AB  - The data in this article outline the methods used for the administration of GET
      73 in the first time-in-human manuscript entitled "Phase I randomized clinical
      trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5
      negative allosteric modulator GET 73 following single and repeated doses in
      healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided
      in two different manners. The first series of tables provided includes procedural
      information about the experiments conducted. The next series of tables provided
      includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET
      2. This set of data is comprised by two experiments: Experiment 1 references a
      single ascending dose administration of GET 73 and Experiment 2 references a
      repeated ascending dose administration of GET 73.

PMID- 29214203
TI  - Supplementary data for the mechanism for cleavage of three typical glucosidic
      bonds induced by hydroxyl free radical.
AB  - The data presented in this article are related to the research article entitled
      "The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl
      free radical" (Dai et al., 2017) [1]. This article includes the structures of
      three kinds of disaccharides such as maltose, fructose and cellobiose, the
      diagrammatic sketch of the hydrogen abstraction reaction of the disaccharides by
      hydroxyl radical, the structure of the transition states for pyran ring opening
      of moiety A and cleavage of alpha(1->2) glycosidic bond starting from the
      hydrogen abstraction of C6-H in moiety A of sucrose, the transition state
      structure for cleavage of alpha(1->2) glycosidic bond starting from the hydrogen
      abstraction of C1'-H in moiety B of sucrose, the transition state structure,
      sketch for the reaction process and relative energy change of the reaction
      pathway for direct cleavage of alpha(1->4) glycosidic bond starting from hydrogen
      abstraction of C6'-H of moiety B of maltose.

PMID- 29214204
TI  - Revealing the Diversity of Introduced Coffea canephora Germplasm in Ecuador:
      Towards a National Strategy to Improve Robusta.
AB  - Genetic resources of Coffea canephora have been introduced in several tropical
      countries with potential for crop development. In Ecuador, the species has been
      cultivated since the mid-20th century. However, little is known about the
      diversity and genetic structure of introduced germplasm. This paper provides an
      overview of the genetic and phenotypic diversity of C. canephora in Ecuador and
      some proposals for implementing a breeding program. Twelve SSR markers were used
      to analyze 1491 plants of C. canephora grown in different living collections in
      Ecuador, compared to 29 genotypes representing the main genetic and geographic
      diversity groups identified within the species. Results indicated that most of
      the genotypes introduced are of Congolese origin, with accessions from both main
      subgroups, SG1 and SG2. Some genotypes were classed as hybrids between both
      subgroups. Substantial phenotypic diversity was also found, and correlations were
      observed with genetic diversity. Ecuadorian Robusta coffee displays wide genetic
      diversity and we propose some ways of improving Robusta in Ecuador. A breeding
      program could be based on three operations: the choice of elite clones, the
      introduction of new material from other countries (Ivory Coast, Uganda), and the
      creation of new hybrid material using genotypes from the different diversity
      groups.

PMID- 29214205
TI  - Simple eye-movement feedback during visual search is not helpful.
AB  - Searching for targets in the visual world, or visual search, is something we all
      do every day. We frequently make 'false-negative' errors, wherein we erroneously
      conclude a target was absent when one was, in fact, present. These sorts of
      errors can have tremendous costs, as when signs of cancers are missed in
      diagnostic radiology. Prior research has characterized the cause of many of these
      errors as being due to failure to completely search the area where targets may be
      present; indeed, roughly one-third of chest nodules missed in lung cancer
      screening are never fixated (Drew, Vo, Olwal, Jacobson, Seltzer and Wolfe,
      Journal of Vision 13:3, 2013). This suggests that observers do not have a good
      representation of what areas have and have not been searched prior to declaring
      an area target free. Therefore, in six experiments, we sought to examine the
      utility of reducing the uncertainty with respect to what areas had been examined
      via online eye-tracking feedback. We hypothesized that providing information
      about what areas had or had not been examined would lead to lower rates of false
      negatives or more efficient search, namely faster response times with no cost on
      target detection accuracy. Neither of these predictions held true. Over six
      experiments, online eye-tracking feedback did not yield any reliable performance
      benefits.

PMID- 29214206
TI  - The effect of testing can increase or decrease misinformation susceptibility
      depending on the retention interval.
AB  - Research has consistently demonstrated that testing prior to the presentation of
      misleading post-event information, within the context of a standard eyewitness
      misinformation paradigm, results in an increase in the misinformation effect. The
      present study investigated whether changes in misinformation susceptibility in
      the context of interim testing are affected by retention interval differences
      between misinformation presentation and final testing. Further, this study tested
      possible divergences in original and post-event learning between conditions where
      elaboration in processing of critical details was encouraged either indirectly,
      via interim testing, or directly, by visually emphasizing critical details. In
      two experiments, we compared three groups of participants. All participants were
      exposed to an event, presented with misleading post-event misinformation, and
      then given a final test on the original event. One group was given an interim
      test between the original event and the post-event synopsis. A second was
      presented with a post-event synopsis in which critical details were visually
      emphasized. A third group served as a baseline comparison group for which
      synopsis processing was not manipulated. All experimental phases occurred in a
      single session in Experiment 1. A 48-hour retention interval was inserted between
      the post-event synopsis and final test in Experiment 2. In Experiment 1, we found
      that interim testing and emphasizing critical details increased misinformation
      susceptibility as compared to that found in the standard misinformation group. In
      Experiment 2, misinformation susceptibility was reduced in the interim testing
      group. These results suggest that interim testing and emphasizing critical
      details influence the rate of original detail forgetting. At a longer retention
      interval, the benefits of testing in learning emerged.

PMID- 29214208
TI  - Eye movement feedback fails to improve visual search performance.
AB  - Many real-world searches (e.g., radiology and baggage screening) have rare
      targets. When targets are rare, observers perform rapid, incomplete searches,
      leading to higher miss rates. To improve search for rare (10% prevalence)
      targets, we provided eye movement feedback (EMF) to observers during their
      searches. Although the nature of the EMF varied across experiments, each method
      informed observers about the regions of the display that had not yet been
      inspected. We hypothesized that feedback would help guide attention to unsearched
      areas and increase the proportion of the display searched before making a target
      absent response, thereby increasing accuracy. An eye tracker was used to mark
      fixated areas by either removing a semiopaque gray overlay (Experiments 1 and 4)
      as portions of the display were fixated or by adding the overlay once the eye
      left a segment of the image (Experiments 2 and 4). Experiment 3 provided
      automated EMF, such that a new region was uncovered every 540 milliseconds.
      Across experiments, we varied whether people searched for "Waldo" in images from
      "Where's Waldo?" search books or searched for a T among offset Ls. We found weak
      evidence that EMF improves accuracy in Experiment 1. However, in the remaining
      experiments, EMF had no effect (Experiment 4), or even reduced accuracy
      (Experiments 2 and 3). We conclude that the one positive result we found is
      likely a Type I error and that the EMF method that we used is unlikely to improve
      visual search performance.

PMID- 29214207
TI  - What is the role of the film viewer? The effects of narrative comprehension and
      viewing task on gaze control in film.
AB  - Film is ubiquitous, but the processes that guide viewers' attention while viewing
      film narratives are poorly understood. In fact, many film theorists and
      practitioners disagree on whether the film stimulus (bottom-up) or the viewer
      (top-down) is more important in determining how we watch movies. Reading research
      has shown a strong connection between eye movements and comprehension, and scene
      perception studies have shown strong effects of viewing tasks on eye movements,
      but such idiosyncratic top-down control of gaze in film would be anathema to the
      universal control mainstream filmmakers typically aim for. Thus, in two
      experiments we tested whether the eye movements and comprehension relationship
      similarly held in a classic film example, the famous opening scene of Orson
      Welles' Touch of Evil (Welles & Zugsmith, Touch of Evil, 1958). Comprehension
      differences were compared with more volitionally controlled task-based effects on
      eye movements. To investigate the effects of comprehension on eye movements
      during film viewing, we manipulated viewers' comprehension by starting
      participants at different points in a film, and then tracked their eyes. Overall,
      the manipulation created large differences in comprehension, but only produced
      modest differences in eye movements. To amplify top-down effects on eye
      movements, a task manipulation was designed to prioritize peripheral scene
      features: a map task. This task manipulation created large differences in eye
      movements when compared to participants freely viewing the clip for
      comprehension. Thus, to allow for strong, volitional top-down control of eye
      movements in film, task manipulations need to make features that are important to
      narrative comprehension irrelevant to the viewing task. The evidence provided by
      this experimental case study suggests that filmmakers' belief in their ability to
      create systematic gaze behavior across viewers is confirmed, but that this does
      not indicate universally similar comprehension of the film narrative.

PMID- 29214209
TI  - The impact of fillers on lineup performance.
AB  - Filler siphoning theory posits that the presence of fillers (known innocents) in
      a lineup protects an innocent suspect from being chosen by siphoning choices away
      from that innocent suspect. This mechanism has been proposed as an explanation
      for why simultaneous lineups (viewing all lineup members at once) induces better
      performance than showups (one-person identification procedures). We implemented
      filler siphoning in a computational model (WITNESS, Clark, Applied Cognitive
      Psychology 17:629-654, 2003), and explored the impact of the number of fillers
      (lineup size) and filler quality on simultaneous and sequential lineups (viewing
      lineups members in sequence), and compared both to showups. In limited
      situations, we found that filler siphoning can produce a simultaneous lineup
      performance advantage, but one that is insufficient in magnitude to explain
      empirical data. However, the magnitude of the empirical simultaneous lineup
      advantage can be approximated once criterial variability is added to the model.
      But this modification works by negatively impacting showups rather than promoting
      more filler siphoning. In sequential lineups, fillers were found to harm
      performance. Filler siphoning fails to clarify the relationship between
      simultaneous lineups and sequential lineups or showups. By incorporating
      constructs like filler siphoning and criterial variability into a computational
      model, and trying to approximate empirical data, we can sort through explanations
      of eyewitness decision-making, a prerequisite for policy recommendations.

PMID- 29214210
TI  - Excitatory Synaptic Input to Hilar Mossy Cells under Basal and Hyperexcitable
      Conditions.
AB  - Hilar mossy cells (HMCs) in the hippocampus receive glutamatergic input from
      dentate granule cells (DGCs) via mossy fibers (MFs) and back-projections from CA3
      pyramidal neuron collateral axons. Many fundamental features of these excitatory
      synapses have not been characterized in detail despite their potential relevance
      to hippocampal cognitive processing and epilepsy-induced adaptations in circuit
      excitability. In this study, we compared pre- and postsynaptic parameters between
      MF and CA3 inputs to HMCs in young and adult mice of either sex and determined
      the relative contributions of the respective excitatory inputs during in vitro
      and in vivo models of hippocampal hyperexcitability. The two types of excitatory
      synapses both exhibited a modest degree of short-term plasticity, with MF inputs
      to HMCs exhibiting lower paired-pulse (PP) and frequency facilitation than was
      described previously for MF-CA3 pyramidal cell synapses. MF-HMC synapses
      exhibited unitary excitatory synaptic currents (EPSCs) of larger amplitude,
      contained postsynaptic kainate receptors, and had a lower NMDA/AMPA receptor
      ratio compared to CA3-HMC synapses. Pharmacological induction of hippocampal
      hyperexcitability in vitro transformed the abundant but relatively weak CA3-HMC
      connections to very large amplitude spontaneous bursts of compound EPSCs (cEPSCs)
      in young mice (~P20) and, to a lesser degree, in adult mice (~P70). CA3-HMC
      cEPSCs were also observed in slices prepared from mice with spontaneous seizures
      several weeks after intrahippocampal kainate injection. Strong excitation of HMCs
      during synchronous CA3 activity represents an avenue of significant excitatory
      network generation back to DGCs and might be important in generating epileptic
      networks.

PMID- 29214211
TI  - Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of
      LRRK2 Parkinson's disease.
AB  - In a number of Drosophila models of genetic Parkinson's disease (PD) flies climb
      more slowly than wild-type controls. However, this assay does not distinguish
      effects of PD-related genes on gravity sensation, "arousal", central pattern
      generation of leg movements, or muscle. To address this problem, we have
      developed an assay for the fly proboscis extension response (PER). This is
      attractive because the PER has a simple, well-identified reflex neural circuit,
      in which sucrose sensing neurons activate a pair of "command interneurons", and
      thence motoneurons whose activity contracts the proboscis muscle. This circuit is
      modulated by a single dopaminergic neuron (TH-VUM). We find that expressing
      either the G2019S or I2020T (but not R1441C, or kinase dead) forms of human LRRK2
      in dopaminergic neurons reduces the percentage of flies that initially respond to
      sucrose stimulation. This is rescued fully by feeding l-DOPA and partially by
      feeding kinase inhibitors, targeted to LRRK2 (LRRK2-IN-1 and BMPPB-32). High
      speed video shows that G2019S expression in dopaminergic neurons slows the speed
      of proboscis extension, makes its duration more variable, and increases the
      tremor. Testing subsets of dopaminergic neurons suggests that the single TH-VUM
      neuron is likely most important in this phenotype. We conclude the Drosophila PER
      provides an excellent model of LRRK2 motor deficits showing bradykinesia,
      akinesia, hypokinesia, and increased tremor, with the possibility to localize
      changes in neural signaling.

PMID- 29214212
TI  - Erratum: Brain structural plasticity with spaceflight.
AB  - [This corrects the article DOI: 10.1038/s41526-016-0001-9.].

PMID- 29214214
TI  - Molecular changes in premenopausal oestrogen receptor-positive primary breast
      cancer in Vietnamese women after oophorectomy.
AB  - For premenopausal women with primary ER + breast cancer, oophorectomy (OvX) is an
      evidence-based cost-effective option and is standard treatment in many countries.
      However, there is virtually no data describing the effects of OvX on breast
      tumour biology. We therefore, characterised the endocrine and genome-wide
      transcriptional impact of OvX in 56 premenopausal women with ER + breast cancer
      for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from
      406 +/- 41 to 20.7 +/- 2.6 pmol/l (mean +/- sem) 24 h after OvX, and to 8.1 +/-
      0.8 pmol/l 2 weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours.
      The expression of 655 genes changed significantly (FDR < 1%) with an absolute
      mean fold-change (FC) >= 1.25 (257 up, 398 down). Archetypal oestrogen-regulated
      genes (TFF1, GREB1, PGR and PDZK1) showed large decreases in expression (FC =
      0.20-0.69; p < 1e-6-1e-7). Proliferation-associated genes (e.g. TOP2A, AURKA and
      UBE2C) were also strongly downregulated (FC = 0.38-0.56; p < 1e-7) along with
      putative progesterone-regulated genes (e.g. FKBP4, MYB; FC = 0.64-0.68; p < 1e-4
      1e-7). The gene expression changes did not differ according to HER2 status and
      correlated strongly with the changes reported previously after aromatase
      inhibitor (AI) treatment in postmenopausal women (rho = 0.55, p < 1e-04).
      However, after OvX the mean FC was significantly higher compared to AI (p < 1e
      04). In conclusion, changes in tumoural gene expression after OvX were largely
      similar, but of a greater magnitude to those observed after AI in postmenopausal
      patients; however, OvX appeared to have a greater effect on progesterone
      regulated genes than AI.

PMID- 29214213
TI  - Therapeutic Potential of Arsenic Trioxide (ATO) in Treatment of Hepatocellular
      Carcinoma: Role of Oxidative Stress in ATO-Induced Apoptosis.
AB  - Hepatocellular carcinoma (HCC), the dominant form of primary liver cancer, is the
      sixth most common cancer in the world with more than 700,000 people diagnosed
      annually. Arsenic trioxide (ATO) has been shown to be a potent anticancer agent
      in various carcinomas, proving particularly effective in the clinical treatment
      of relapsed and refractory acute promyelocytic leukemia. However, its bioactivity
      and molecular mechanisms against HCC has not been fully studied. Using human HCC
      (HepG2) cells as a test model, we studied the effects of ATO and examined the
      role of oxidative stress (OS) and apoptosis in cytotoxicity. OS biomarkers showed
      a significant increase (p< 0.05) of malondialdehyde concentrations, and a gradual
      decrease of antioxidant enzymes (GPx & CAT) activities with increasing ATO doses.
      Flow cytometry data showed a dose dependent increase in annex in V positive cells
      and caspase 3 activities. These results were confirmed by data of the DNA
      laddering assay showing a clear evidence of nucleosomal DNA fragmentation, as
      well as data from Western blotting showing a significant modulation of specific
      apoptotic related proteins, including the activation of p53 and p21 expression
      and the down-regulation of Bcl-2 expression in ATO-treated cells. Taken together,
      our research demonstrates that ATO has a potential therapeutic effect against
      HCC, and its cytotoxicity may be mediated via oxidative stress and activation of
      the mitochondrial or intrinsic pathway of apoptosis.

PMID- 29214216
TI  - Structural insight into the methyltransfer mechanism of the bifunctional Trm5.
AB  - The wyosine derivatives present at position 37 in transfer RNAs (tRNAs) are
      critical for reading frame maintenance. The methyltransferase Trm5a from
      Pyrococcus abyssi (PaTrm5a) plays a key role in this hypermodification process in
      generating m1G37 and imG2, two products of the wyosine biosynthetic pathway,
      through two methyl transfers to distinct substrates, but the mechanism is
      currently unknown. We report two cocrystal structures of PaTrm5a in complex with
      tRNAPhe and reveal the structural basis for substrate recognition, which was
      supported by in vitro activity assays. The crystal structures showed that the D1
      domain of the enzyme undergoes large conformational changes upon the binding of
      tRNA. The deletion of this domain greatly reduces the affinity and activity of
      PaTrm5a toward its RNA substrate, indicating that the enzyme recognizes the
      overall shape of tRNA. Using the small-angle x-ray scattering technique and
      crystallographic analysis, we discovered that PaTrm5a adopts distinct open
      conformations before and after the binding of tRNA. Last, through structure
      comparison with its ortholog Methanococcus jannaschii Trm5b (MjTrm5b), we propose
      a reaction mechanism for the double methylation capability of this unique enzyme.

PMID- 29214215
TI  - Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast.
AB  - Metaplastic breast cancer (MBC) is a rare special histologic type of triple
      negative breast cancer, characterized by the presence of neoplastic cells showing
      differentiation towards squamous epithelium and/or mesenchymal elements. Here we
      sought to define whether histologically distinct subgroups of MBCs would be
      underpinned by distinct genomic and/or transcriptomic alterations. Microarray
      based copy number profiling identified limited but significant differences
      between the distinct MBC subtypes studied here, despite the limited sample size
      (n = 17). In particular, we found that, compared to MBCs with chondroid or
      squamous cell metaplasia, MBCs with spindle cell differentiation less frequently
      harbored gain of 7q11.22-23 encompassing CLDN3 and CLDN4, consistent with their
      lower expression of claudins and their association with the claudin-low molecular
      classification. Microarray-based and RNA-sequencing-based gene expression
      profiling revealed that MBCs with spindle cell differentiation differ from MBCs
      with chondroid or squamous cell metaplasia on the expression of epithelial-to
      mesenchymal transition-related genes, including down-regulation of CDH1 and
      EPCAM. In addition, RNA-sequencing revealed that the histologic patterns observed
      in MBCs are unlikely to be underpinned by a highly recurrent expressed fusion
      gene or a pathognomonic expressed mutation in cancer genes. Loss of PTEN
      expression or mutations affecting PIK3CA or TSC2 observed in 8/17 MBCs support
      the contention that PI3K pathway activation plays a role in the development of
      MBCs. Our data demonstrate that despite harboring largely similar patterns of
      gene copy number alterations, MBCs with spindle cell, chondroid and squamous
      differentiation are distinct at the transcriptomic level but are unlikely to be
      defined by specific pathognomonic genetic alterations.

PMID- 29214217
TI  - Symmetry-breaking inelastic wave-mixing atomic magnetometry.
AB  - The nonlinear magneto-optical rotation (NMOR) effect has prolific applications
      ranging from precision mapping of Earth's magnetic field to biomagnetic sensing.
      Studies on collisional spin relaxation effects have led to ultrahigh magnetic
      field sensitivities using a single-beam Lambda scheme with state-of-the-art
      magnetic shielding/compensation techniques. However, the NMOR effect in this
      widely used single-beam Lambda scheme is peculiarly small, requiring complex
      radio-frequency phase-locking protocols. We show the presence of a previously
      unknown energy symmetry-based nonlinear propagation blockade and demonstrate an
      optical inelastic wave-mixing NMOR technique that breaks this NMOR blockade,
      resulting in an NMOR optical signal-to-noise ratio (SNR) enhancement of more than
      two orders of magnitude never before seen with the single-beam Lambda scheme. The
      large SNR enhancement was achieved simultaneously with a nearly two orders of
      magnitude reduction in laser power while preserving the magnetic resonance
      linewidth. This new method may open a myriad of applications ranging from
      biomagnetic imaging to precision measurement of the magnetic properties of
      subatomic particles.

PMID- 29214218
TI  - Skiving stacked sheets of paper into test paper for rapid and multiplexed assay.
AB  - This paper shows that stacked sheets of paper preincubated with different
      biological reagents and skiving them into uniform test paper sheets allow mass
      manufacturing of multiplexed immunoassay devices and simultaneous detection of
      multiplex targets that can be read out by a barcode scanner. The thickness of one
      sheet of paper can form the width of a module for the barcode; when stacked,
      these sheets of paper can form a series of barcodes representing the targets,
      depending on the color contrast provided by a colored precipitate of an
      immunoassay. The uniform thickness of sheets of paper allows high-quality signal
      readout. The manufacturing method allows highly efficient fabrication of the
      materials and substrates for a straightforward assay of targets that range from
      drugs of abuse to biomarkers of blood-transmitted infections. In addition, as a
      novel alternative to the conventional point-of-care testing method, the paper
      based barcode assay system can provide highly efficient, accurate, and objective
      diagnoses.

PMID- 29214219
TI  - 3D printing of bacteria into functional complex materials.
AB  - Despite recent advances to control the spatial composition and dynamic
      functionalities of bacteria embedded in materials, bacterial localization into
      complex three-dimensional (3D) geometries remains a major challenge. We
      demonstrate a 3D printing approach to create bacteria-derived functional
      materials by combining the natural diverse metabolism of bacteria with the shape
      design freedom of additive manufacturing. To achieve this, we embedded bacteria
      in a biocompatible and functionalized 3D printing ink and printed two types of
      "living materials" capable of degrading pollutants and of producing medically
      relevant bacterial cellulose. With this versatile bacteria-printing platform,
      complex materials displaying spatially specific compositions, geometry, and
      properties not accessed by standard technologies can be assembled from bottom up
      for new biotechnological and biomedical applications.

PMID- 29214220
TI  - Metal-organic frameworks and their derived materials for electrochemical energy
      storage and conversion: Promises and challenges.
AB  - In addition to their conventional uses, metal-organic frameworks (MOFs) have
      recently emerged as an interesting class of functional materials and precursors
      of inorganic materials for electrochemical energy storage and conversion
      technologies. This class of MOF-related materials can be broadly categorized into
      two groups: pristine MOF-based materials and MOF-derived functional materials.
      Although the diversity in composition and structure leads to diverse and tunable
      functionalities of MOF-based materials, it appears that much more effort in this
      emerging field is devoted to synthesizing MOF-derived materials for
      electrochemical applications. This is in view of two main drawbacks of MOF-based
      materials: the low conductivity nature and the stability issue. On the contrary,
      MOF-derived synthesis strategies have substantial advantages in controlling the
      composition and structure of MOF-derived materials. From this perspective, we
      review some emerging applications of both groups of MOF-related materials as
      electrode materials for rechargeable batteries and electrochemical capacitors,
      efficient electrocatalysts, and even electrolytes for electrochemical devices. By
      highlighting the advantages and challenges of each class of materials for
      different applications, we hope to shed some light on the future development of
      this highly exciting area.

PMID- 29214221
TI  - Neurobiology of KB220Z-Glutaminergic-Dopaminergic Optimization Complex [GDOC] as
      a Liquid Nano: Clinical Activation of Brain in a Highly Functional Clinician
      Improving Focus, Motivation and Overall Sensory Input Following Chronic Intake.
AB  - Background: With neurogenetic and epigenetic tools utilized in research and
      neuroimaging, we are unraveling the mysteries of brain function, especially as it
      relates to Reward Deficiency (RDS). We encourage the development of
      pharmaceuticals or nutraceuticals that promote a reduction in dopamine resistance
      and balance brain neurochemistry, leading to dopamine homeostasis. We disclose
      self-assessment of a highly functional professional under work-related stress
      following KB220Z use, a liquid (aqua) nano glutaminergic-dopaminergic
      optimization complex (GDOC). Case presentation: Subject took GDOC for one month.
      Subject self-administered GDOC using one-half-ounce twice a day. During first
      three days, unique brain activation occurred; resembling white noise after 30
      minutes and sensation was strong for 45 minutes and then dissipated. He described
      effect as if his eyesight improved slightly and pointed out that his sense of
      smell and sleep greatly improved. Subject experienced a calming effect similar to
      meditation that could be linked to dopamine release. He also reported control of
      going over the edge after a hard day's work, which was coupled with a slight
      increase in energy, increased motivation to work, increased focus and multi
      tasking, with clearer purpose of task at hand. Subject felt less inhibited in a
      social setting and suggested Syndrome that GDOC increased his Behavior Activating
      System (reward), while having a decrease in the Behavior Inhibition System
      (caution). Conclusion: These results and other related studies reveal an improved
      mood, work-related focus, and sleep. These effects as a subjective feeling of
      brain activation maybe due to direct or indirect dopaminergic interaction. While
      this case is encouraging, we must await more research in a larger randomized
      placebo-controlled study to map the role of GDOC, especially in a nano-sized
      product, to determine the possible effects on circuit inhibitory control and
      memory banks and the induction of dopamine homeostasis independent of either hypo
      or hyper-dopaminergic traits/states.

PMID- 29214222
TI  - Reasons to pursue a career in medicine: a qualitative study in Sierra Leone.
AB  - Background: Many low-income and crises-affected countries like Sierra Leone
      struggle with the recruitment and retention of their health professionals,
      particularly nurses and doctors. There are multiple factors that influence the
      'recruitment to retention' pipeline. The first stage of an exploration into the
      issues influencing the availability of qualified health care workers may focus on
      the aspects which influence their entry into relevant educational programmes.
      This paper explores the reasons given by junior doctors in Sierra Leone for
      wanting to become a doctor. It also describes entry procedures into undergraduate
      medical education. Methods: In-depth interviews were conducted with purposively
      sampled junior doctors (n = 15) from the only medical school in Sierra Leone in
      October 2013. Digital diaries and two follow-up interviews were used to explore
      their evolving career experiences and aspirations until November 2016. In
      addition, semi-structured interviews with key informants (n = 20), including
      senior teaching staff at the medical school (n = 7), were conducted. Thematic
      analysis was used to explore linkages and themes across cases. Results: Six
      themes were identified. The most commonly mentioned reasons for wanting to become
      a doctor were a desire to help (theme 4) and the influence of family and friends,
      via role modelling (theme 2) and verbal encouragement (theme 3). Other motives
      were an interest from a young age (theme 1), being attracted by the job prospects
      (theme 5), and having an intellectual and science capacity (theme 6). Junior
      doctors gave at least two and up to six reasons for applying to enter the medical
      profession. Doctors were allowed entry to the medical school largely based on
      their previous academic performance. Conclusions: This study showed that multiple
      reasons underlie the decision to apply for entrance to medical school and the
      decision to enter medicine is complex. These findings may inform the review of
      future admission procedures by the medical school in Sierra Leone and similar
      settings, which is a crucial step in addressing the human resource needs for
      healthcare that currently exist.

PMID- 29214223
TI  - Novel elvitegravir nanoformulation approach to suppress the viral load in HIV
      infected macrophages.
AB  - Purpose: Monocytes serve as sanctuary sites for HIV-1 from which virus is
      difficult to be eliminated. Therefore, an effective viral suppression in
      monocytes is critical for effective antiretroviral therapy (ART). This study
      focuses on a new strategy using nanoformulation to optimize the efficacy of ART
      drugs in HIV-infected monocytes. Methods: Poly(lactic-co-glycolic acid) (PLGA)
      based elvitegravir nanoparticles (PLGA-EVG) were prepared by nano-precipitation
      technique. The physicochemical properties of PLGA-EVG were characterized using
      transmission electron microscopy, dynamic light scattering, and Fourier-transform
      infrared spectroscopy. Cellular uptake study was performed by fluorescence
      microscopy and flow cytometry. All in vitro experiments were performed by using
      HIV-infected monocytic cell lines U1 and HIV-infected primary macrophages.
      Elvitegravir quantification was performed using LC-MS/MS. HIV viral replication
      was assessed by using p24 ELISA. Results: We developed a PLGA-EVG nanoparticle
      formulation with particle size of ~ 47 nm from transmission electron microscopy
      and zeta potential of ~ 6.74 mV from dynamic light scattering. These
      nanoparticles demonstrated a time- and concentration-dependent uptakes in
      monocytes. PLGA-EVG formulation showed a ~ 2 times higher intracellular
      internalization of EVG than control group (EVG alone). PLGA-EVG nanoparticles
      also demonstrated superior viral suppression over control for a prolonged period
      of time. Conclusions: PLGA-based EVG nanoformulation increased the intracellular
      uptake of EVG, as well as enhanced viral suppression in HIV-infected macrophages,
      suggesting its potential for improved HIV treatment in monocytic cells.

PMID- 29214224
TI  - Mutation network-based understanding of pleiotropic and epistatic mutational
      behavior of Enterococcus faecalis FMN-dependent azoreductase.
AB  - We previously identified a highly active homodimeric FMN-dependent NADH-preferred
      azoreductase (AzoA) from Enterococcus faecalis, which cleaves the azo bonds (R
      N?N-R) of diverse azo dyes, and determined its crystal structure. The preliminary
      network-based mutational analysis suggested that the two residues, Arg-21 and Asn
      121, have an apparent mutational potential for fine-tuning of AzoA, based on
      their beneficial pleiotropic feedbacks. However, epistasis between the two
      promising mutational spots in AzoA has not been obtained in terms of substrate
      binding and azoreductase activity. In this study, we further quantified,
      visualized, and described the pleiotropic and/or epistatic behavior of six single
      or double mutations at the positions, Arg-21 and Asn-121, as a further research
      endeavor for beneficial fine-tuning of AzoA. Based on this network-based
      mutational analysis, we showed that pleiotropy and epistasis are common,
      sensitive, and complex mutational behaviors, depending mainly on the structural
      and functional responsibility and the physicochemical properties of the
      residue(s) in AzoA.

PMID- 29214225
TI  - Crocin, a plant-derived carotenoid, modulates microglial reactivity.
AB  - Microglia activation plays an important role in immune responses in the CNS
      including the retina. Crocin, a plant-derived carotenoid, has been reported to
      possess anti-inflammatory, anti-apoptotic and anti-oxidative capacity in models
      of retinal damage and degeneration. If these neuroprotective effects could be
      mediated by direct modulation of microglial cells is unclear. Here, we examined
      the direct effects of crocin on key functions and pro-inflammatory gene
      expression in lipopolysaccharide (LPS)-activated BV-2 microglia. We found that
      crocin stimulation strongly promoted filopodia formation and markedly increased
      microglial phagocytosis, two important parameters relevant for physiological
      microglia functions. Moreover, crocin significantly reduced gene expression of
      the pro-inflammatory markers IL6, CCL2, and iNOS in LPS-challenged BV-2 cells and
      potently blocked NO production in these microglia. The observed immunomodulatory
      effects of crocin were not mediated by general inhibition of NFkB nuclear
      translocation. Our findings indicate that many of the anti-inflammatory effects
      of crocin demonstrated in animal models of neuronal degeneration could be
      mediated by its direct effects on microglia homeostasis.

PMID- 29214226
TI  - Derivatives (halogen, nitro and amino) of 8-hydroxyquinoline with highly potent
      antimicrobial and antioxidant activities.
AB  - 8-Hydroxyquinoline (8HQ) compounds have been reported to possess diverse
      bioactivities. In recent years, drug repositioning has gained considerable
      attention in drug discovery and development. Herein, 8HQ (1) and its derivatives
      (2-9) bearing various substituents (amino, nitro, cyano and halogen) were
      investigated for their antimicrobial against 27 microorganisms (agar dilution
      method) and antioxidant (DPPH method) activities. The parent 8HQ (1) exerted a
      highly potent antimicrobial activity against Gram-positive bacteria including
      diploid fungi and yeast with MIC values in the range of 3.44-13.78 MUM. Moreover,
      the halogenated 8HQ, especially 7-bromo-8HQ (4) and clioquinol (6), displayed a
      high antigrowth activity against Gram-negative bacteria compared with the parent
      compound (1). Apparently, the derivatives with a relatively high safely index,
      e.g., nitroxoline (2), exhibited strong antibacterial activity against Aeromonas
      hydrophila (MIC=5.26 MUM) and selectively inhibited the growth of P. aeruginosa
      with the MIC value of 84.14 MUM; cloxyquin (3) showed a strong activity against
      Listseria monocytogenes and Plesiomonas shigelloides with MIC values of 5.57 and
      11.14 MUM, respectively. Most compounds displayed an antioxidant activity.
      Specifically, 5-amino-8HQ (8) was shown to be the most potent antioxidant
      (IC50=8.70 MUM) compared with the positive control (alpha-tocopherol) with IC50
      of 13.47 MUM. The findings reveal that 8HQ derivatives are potential candidates
      to be further developed as antimicrobial and antioxidant agents.

PMID- 29214227
TI  - Potentiating effect of glabridin from Glycyrrhiza glabra on GABAA receptors.
AB  - Extracts from Glycyrrhiza are traditionally used for the treatment of insomnia
      and anxiety. Glabridin is one of the main flavonoid compounds from Glycyrrhiza
      glabra and displays a broad range of biological properties. In the present work,
      we investigated the effect of glabridin on GABAA receptors. For this purpose, we
      employed the two-electrode voltage-clamp technique on Xenopus laevis oocytes
      expressing recombinant GABAA receptors. Through this approach, we observed that
      glabridin presents a strong potentiating effect on GABAA alpha1beta(1-3)gamma2
      receptors. The potentiation was slightly dependent on the beta subunit and was
      most pronounced at the alpha1beta2gamma2 subunit combination, which forms the
      most abundant GABAA receptor in the CNS. Glabridin potentiated with an EC50 of
      6.3+/-1.7 uM and decreased the EC50 of the receptor for GABA by approximately 12
      fold. The potentiating effect of glabridin is flumazenil-insensitive and does not
      require the benzodiazepine binding site. Glabridin acts on the beta subunit of
      GABAA receptors by a mechanism involving the M286 residue, which is a key amino
      acid at the binding site for general anesthetics, such as propofol and etomidate.
      Our results demonstrate that GABAA receptors are strongly potentiated by one of
      the main flavonoid compounds from Glycyrrhiza glabra and suggest that glabridin
      could contribute to the reported hypnotic effect of Glycyrrhiza extracts.

PMID- 29214228
TI  - A glucose/mannose binding lectin from litchi (Litchi chinensis) seeds:
      Biochemical and biophysical characterizations.
AB  - Background: Lectins are highly important biomolecules to study several biological
      processes. A novel alpha-D-glucose/mannose specific lectin was isolated from the
      seeds of litchi fruits (Litchi chinensis) and its various biophysical and
      biochemical properties were studied. Methods: Purification was done by successive
      Sephadex G 100 and Con A-Sepharose 4B affinity chromatography. SDS-PAGE, Surface
      Plasmon Resonance (SPR), steady state absorbance, fluorescence, time-correlated
      single-photon counting, circular dichroism and antibiofilm activity by measuring
      total protein estimation and azocasein degradation assay have been performed.
      Results: The purified lectin is a homodimer of molecular mass ~ 54 kDa. The
      amount of lectin required for hemagglutination of normal human O erythrocytes was
      6.72 ug/ml. Among the saccharides tested, Man-alpha-(1,6)-Man was found to be the
      most potent inhibitor (0.01 mM) determined by hemagglutination inhibition assay.
      Steady state and time resolved fluorescence measurements revealed that litchi
      lectin formed ground state complex with maltose (Ka=4.9 (+/-0.2)*104 M-1), which
      indicated static quenching (Stern-Volmer (SV) constant Ksv=4.6 (+/-0.2)*104 M-1).
      CD measurements demonstrated that litchi lectin showed no overall conformational
      change during the binding process with maltose. The lectin showed antibiofilm
      activity against Pseudomonus aeruginosa. Conclusions: A novel homodimeric lectin
      has been purified from the seeds of litchi fruits (Litchi chinensis) having
      specificity for alpha-d-glucose/mannose. The thermodynamics and conformational
      aspects of its interaction with maltose have been studied in detail. The
      antibiofilm activity of this lectin towards Pseudomonus aeruginosa has been
      explored. General significance: The newly identified litchi lectin is highly
      specific for alpha-d-glucose/mannose with an important antibiofilm activity
      towards Pseudomonus aeruginosa.

PMID- 29214229
TI  - Feasibility trial of a psychoeducational intervention for parents with
      personality difficulties: The Helping Families Programme.
AB  - The Helping Families Programme is a psychoeducational parenting intervention that
      aims to improve outcomes and engagement for parents affected by clinically
      significant personality difficulties. This is achieved by working collaboratively
      with parents to explore ways in which their emotional and relational difficulties
      impact on parenting and child functioning, and to identify meaningful and
      realistic goals for change. The intervention is delivered via one-to-one sessions
      at weekly intervals over a period of 16 weeks. This protocol describes a two-arm
      parallel RCT in which consenting parents are randomly allocated in a 1:1 ratio to
      either the Helping Families Programme plus the usual services that the parent may
      be receiving from their mental health and/or social care providers, or to
      standard care (usual services plus a brief parenting advice session). The primary
      clinical outcome will be child behaviour. Secondary clinical outcomes will be
      child and parental mental health, parenting satisfaction, parenting behaviour and
      therapeutic alliance. Health economic measures will be collected on quality of
      life and service use. Outcome measures will be collected at the initial
      assessment stage, after the intervention is completed and at 6-month follow-up by
      research staff blind to group allocation. Trial feasibility will be assessed
      using rates of trial participation at the three time points and intervention
      uptake, attendance and retention. A parallel process evaluation will use
      qualitative interviews to ascertain key-workers' and parent participants'
      experiences of intervention delivery and trial participation. The results of this
      feasibility study will determine the appropriateness of proceeding to a full
      scale trial.

PMID- 29214230
TI  - Cytotoxicity of Endocytosis and Efflux Inhibitors in the BeWo Cell Line.
AB  - Aims: The purpose of this study was to determine the cell viability and
      cytotoxicity of various endocytosis and efflux inhibitors which can be used to
      determine transport and uptake mechanisms in the BeWo (b30 clone) human placental
      trophoblast cell line. Ethanol and dimethylsulfoxide (DMSO) were also studied
      since they are often used as cosolvents for administration of these inhibitors.
      Methodology: The water-soluble tetrazolium-1 (WST-1) assay was used to quantify
      cell viability and the lactate dehydrogenase (LDH) assay was used to determine
      cytotoxicity. Results: By the WST-1 assay, reduced cell viability was observed
      following 4 hours of exposure to chlorpromazine (10 MUg/mL), colchicine (1 mM),
      filipin (3 MUg/mL), gentamicin (2 mM), GF120918 (1 MUM), methyl-beta-cyclodextrin
      (5 mM), and verapamil (100 MUM). By the LDH assay, however, no cytotoxicity was
      observed after 4 hours of exposure to the aforementioned compounds. Amiloride
      (500 MUM), ethanol (up to 0.1% v/v), and DMSO (up to 0.1% v/v) did not reduce
      cell viability nor induce cytotoxicity. Conclusion: This information is valuable
      when selecting potential inhibitors of endocytosis and efflux and the selection
      of time points for mechanistic studies.

PMID- 29214231
TI  - Ab initio chemical safety assessment: A workflow based on exposure considerations
      and non-animal methods.
AB  - We describe and illustrate a workflow for chemical safety assessment that
      completely avoids animal testing. The workflow, which was developed within the
      SEURAT-1 initiative, is designed to be applicable to cosmetic ingredients as well
      as to other types of chemicals, e.g. active ingredients in plant protection
      products, biocides or pharmaceuticals. The aim of this work was to develop a
      workflow to assess chemical safety without relying on any animal testing, but
      instead constructing a hypothesis based on existing data, in silico modelling,
      biokinetic considerations and then by targeted non-animal testing. For
      illustrative purposes, we consider a hypothetical new ingredient x as a new
      component in a body lotion formulation. The workflow is divided into tiers in
      which points of departure are established through in vitro testing and in silico
      prediction, as the basis for estimating a safe external dose in a repeated use
      scenario. The workflow includes a series of possible exit (decision) points, with
      increasing levels of confidence, based on the sequential application of the
      Threshold of Toxicological (TTC) approach, read-across, followed by an "ab
      initio" assessment, in which chemical safety is determined entirely by new in
      vitro testing and in vitro to in vivo extrapolation by means of mathematical
      modelling. We believe that this workflow could be applied as a tool to inform
      targeted and toxicologically relevant in vitro testing, where necessary, and to
      gain confidence in safety decision making without the need for animal testing.

PMID- 29214232
TI  - Hybrid Protein-Glycosaminoglycan Hydrogels Promote Chondrogenic Stem Cell
      Differentiation.
AB  - Gelatin-hyaluronic acid (Gel-HA) hybrid hydrogels have been proposed as matrices
      for tissue engineering because of their ability to mimic the architecture of the
      extracellular matrix. Our aim was to explore whether tyramine conjugates of Gel
      and HA, producing injectable hydrogels, are able to induce a particular phenotype
      of encapsulated human mesenchymal stem cells without the need for growth factors.
      While pure Gel allowed good cell adhesion without remarkable differentiation and
      pure HA triggered chondrogenic differentiation without cell spreading, the
      hybrids, especially those rich in HA, promoted chondrogenic differentiation as
      well as cell proliferation and adhesion. Secretion of chondrogenic markers such
      as aggrecan, SOX-9, collagen type II, and glycosaminoglycans was observed,
      whereas osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin,
      and lipoproteinlipase, respectively) were not present after 2 weeks in the growth
      medium. The most promising matrix for chondrogenesis seems to be a mixture
      containing 70% HA and 30% Gel as it is the material with the best mechanical
      properties from all compositions tested here, and at the same time, it provides
      an environment suitable for balanced cell adhesion and chondrogenic
      differentiation. Thus, it represents a system that has a high potential to be
      used as the injectable material for cartilage regeneration therapies.

PMID- 29214233
TI  - Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine
      Monophosphate (TMP) with a Dinuclear Copper(II) Receptor.
AB  - Understanding the intermolecular interactions between nucleotides and artificial
      receptors is crucial to understanding the role of nucleic acids in living
      systems. However, direct structural evidence showing precise interactions and
      bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based
      synthetic molecule has not been provided so far. Herein, we present two novel
      crystal structures of uridine monophosphate (UMP) and thymidine monophosphate
      (TMP) complexes with a macrocycle-based dinuclear receptor. Structural
      characterization of these complexes reveals that the receptor recognizes UMP
      through coordinate-covalent interactions with phosphates and pi-pi stackings with
      nucleobases and TMP through coordinate-covalent interactions with phosphate
      groups. Furthermore, the receptor has been shown to effectively bind nucleoside
      monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at
      physiological pH, as investigated by an indicator displacement assay.

PMID- 29214235
TI  - Kinetics and Thermodynamics of DbpA Protein's C-Terminal Domain Interaction with
      RNA.
AB  - DbpA is an Escherichia coli DEAD-box RNA helicase implicated in RNA structural
      isomerization in the peptide bond formation site. In addition to the RecA-like
      catalytic core conserved in all of the members of DEAD-box family, DbpA contains
      a structured C-terminal domain, which is responsible for anchoring DbpA to
      hairpin 92 of 23S ribosomal RNA during the ribosome assembly process. Here,
      surface plasmon resonance was used to determine the equilibrium dissociation
      constant and the microscopic rate constants of the DbpA C-terminal domain
      association and dissociation to a fragment of 23S ribosomal RNA containing
      hairpin 92. Our results show that the DbpA protein's residence time on the RNA is
      10 times longer than the time DbpA requires to hydrolyze one ATP. Thus, our data
      suggest that once bound to the intermediate ribosomal particles via its RNA
      binding domain, DbpA could unwind a number of double-helix substrates before its
      dissociation from the ribosomal particles.

PMID- 29214234
TI  - Magnetic Sensing Potential of Fe3O4 Nanocubes Exceeds That of Fe3O4 Nanospheres.
AB  - This paper highlights the relation between the shape of iron oxide (Fe3O4)
      particles and their magnetic sensing ability. We synthesized Fe3O4 nanocubes and
      nanospheres having tunable sizes via solvothermal and thermal decomposition
      synthesis reactions, respectively, to obtain samples in which the volumes and
      body diagonals/diameters were equivalent. Vibrating sample magnetometry (VSM)
      data showed that the saturation magnetization (Ms) and coercivity of 100-225 nm
      cubic magnetic nanoparticles (MNPs) were, respectively, 1.4-3.0 and 1.1-8.4 times
      those of spherical MNPs on a same-volume and same-body diagonal/diameter basis.
      The Curie temperature for the cubic Fe3O4 MNPs for each size was also higher than
      that of the corresponding spherical MNPs; furthermore, the cubic Fe3O4 MNPs were
      more crystalline than the corresponding spherical MNPs. For applications relying
      on both higher contact area and enhanced magnetic properties, higher-Ms Fe3O4
      nanocubes offer distinct advantages over Fe3O4 nanospheres of the same-volume or
      same-body diagonal/diameter. We evaluated the sensing potential of our
      synthesized MNPs using giant magnetoresistive (GMR) sensing and force-induced
      remnant magnetization spectroscopy (FIRMS). Preliminary data obtained by GMR
      sensing confirmed that the nanocubes exhibited a distinct sensitivity advantage
      over the nanospheres. Similarly, FIRMS data showed that when subjected to the
      same force at the same initial concentration, a greater number of nanocubes
      remained bound to the sensor surface because of higher surface contact area.
      Because greater binding and higher Ms translate to stronger signal and better
      analytical sensitivity, nanocubes are an attractive alternative to nanospheres in
      sensing applications.

PMID- 29214237
TI  - Effects of Cationic Proteins on Gold Nanoparticle/Aptamer Assays.
AB  - Gold nanoparticles (AuNPs) and aptamers are compelling building blocks for
      analytical assays with desired attributes of selectivity and sensitivity and may
      theoretically form the basis of instrument-free color-changing assays for any
      target against which a DNA aptamer has been selected. However, assays for
      proteins based on these components may be subject to significant interferences
      from the interaction of proteins with nanoparticles. We found that for three
      representative protein/aptamer systems-thrombin, apolipoprotein E, and platelet
      derived growth factor-pH-dependent aggregation occurred, even in the absence of
      the aptamer, to differing extents. This effect is most pronounced when proteins
      display net surface charge (i.e., when pH < pI) but can even be observed at pH =
      pI when the protein retains regions of positive charge. These interactions of
      AuNPs and cationic regions on proteins may present an important limitation on the
      development of AuNP-based analytical assays.

PMID- 29214236
TI  - Characterization of Byproducts from Chemical Syntheses of Oligonucleotides
      Containing 1-Methyladenine and 3-Methylcytosine.
AB  - Oligonucleotides serve as important tools for biological, chemical, and medical
      research. The preparation of oligonucleotides through automated solid-phase
      synthesis is well-established. However, identification of byproducts generated
      from DNA synthesis, especially from oligonucleotides containing site-specific
      modifications, is sometimes challenging. Typical high-performance liquid
      chromatography (HPLC), mass spectrometry (MS), and gel electrophoresis methods
      alone are not sufficient for characterizing unexpected byproducts, especially for
      those having identical or very similar molecular weight (MW) to the products. We
      used a rigorous quality control procedure to characterize byproducts generated
      during oligonucleotide syntheses: (1) purify oligonucleotides by different HPLC
      systems; (2) determine exact MW by high-resolution MS; (3) locate modification
      position by MS/MS or exonuclease digestion with matrix-assisted laser desorption
      ionization-time of flight analysis; and (4) conduct, where applicable, enzymatic
      assays. We applied these steps to characterize byproducts in the syntheses of
      oligonucleotides containing biologically important methyl DNA adducts 1
      methyladenine (m1A) and 3-methylcytosine (m3C). In m1A synthesis, we
      differentiated a regioisomeric byproduct 6-methyladenine, which possesses a MW
      identical to uncharged m1A. As for m3C, we identified a deamination byproduct 3
      methyluracil, which is only 1 Da greater than uncharged m3C in the ~4900 Da
      context. The detection of these byproducts would be very challenging if the
      abovementioned procedure was not adopted.

PMID- 29214238
TI  - Redox Regulation of a Gain-of-Function Mutation (N308D) in SHP2 Noonan Syndrome.
AB  - SHP2 (Src homology 2 domain-containing protein tyrosine phosphatase 2; PTPN11) is
      a ubiquitous multidomain, nonreceptor protein tyrosine phosphatase (PTP) that
      plays an important role in diseases such as cancer, diabetes, and Noonan syndrome
      (NS). NS is one of the most common genetic disorders associated with congenital
      heart disease, and approximately half of the patients with Noonan syndrome have
      gain-of-function mutations in SHP2. One of the most common NS mutations is N308D.
      The activity of SHP2, like that of most PTPs, is reversibly inactivated by
      reactive oxygen species (ROS). However, the molecular basis of this inactivation
      and the consequences of NS-related mutations in PTPN11 on ROS-mediated inhibition
      are poorly understood. Here, we investigated the mechanistic and structural
      details of the reversible oxidation of the NS variant SHP2N308D. We show that
      SHP2N308D is more sensitive to oxidation when compared with wild-type SHP2. We
      also show that although the SHP2N308D catalytic domain can be reactivated by
      dithiothreitol as effectively as the wild-type, full-length SHP2N308D is only
      poorly reactivated by comparison. To understand the mechanism of oxidation at a
      molecular level, we determined the crystal structure of oxidized SHP2N308D. The
      structure shows that the catalytic Cys459 residue forms a disulfide bond with
      Cys367, which confirms that Cys367 functions as the "backdoor" cysteine in SHP2.
      Together, our data suggest that the reversible oxidation of SHP2 contributes
      negligibly, if at all, to the symptoms associated with NS.

PMID- 29214239
TI  - Protonation Enhances the Inherent Helix-Forming Propensity of pHLIP.
AB  - Cell-penetrating peptides (CPPs) can be potentially used in targeted delivery of
      therapeutic cargoes. However, their conformation in solution is poorly
      understood. We employed molecular dynamics simulations to probe the structural
      fluctuations of an anionic CPP, pH Low Insertion Peptide (pHLIP), in solution to
      determine the effects of modifications to selected residues on the structure of
      pHLIP. Two types of modifications were tested: (1) protonation of aspartic acid
      residues and (2) point mutations known to affect the acid sensitivity of pHLIP.
      pHLIP samples conformations ranging from coil to helix to sheet, and
      modifications to pHLIP lead to subtle shifts in the balance between these
      conformations. In some instances, pHLIP is as likely to form a helical
      conformation as it is to form an unstructured coil. Understanding the behavior of
      pHLIP in solution is necessary for determining optimal conditions for
      administration of pHLIP and design of promising pHLIP variants.

PMID- 29214240
TI  - New principles for auxetic periodic design.
AB  - We show that, for any given dimension d >= 2, the range of distinct possible
      designs for periodic frameworks with auxetic capabilities is infinite. We rely on
      a purely geometric approach to auxetic trajectories developed within our general
      theory of deformations of periodic frameworks.

PMID- 29214242
TI  - Towards a Sign-Based Indoor Navigation System for People with Visual Impairments.
AB  - Navigation is a challenging task for many travelers with visual impairments.
      While a variety of GPS-enabled tools can provide wayfinding assistance in outdoor
      settings, GPS provides no useful localization information indoors. A variety of
      indoor navigation tools are being developed, but most of them require potentially
      costly physical infrastructure to be installed and maintained, or else the
      creation of detailed visual models of the environment. We report development of a
      new smartphone-based navigation aid, which combines inertial sensing, computer
      vision and floor plan information to estimate the user's location with no
      additional physical infrastructure and requiring only the locations of signs
      relative to the floor plan. A formative study was conducted with three blind
      volunteer participants demonstrating the feasibility of the approach and
      highlighting the areas needing improvement.

PMID- 29214241
TI  - Text Messaging May Engage and Benefit Adults with Type 2 Diabetes Regardless of
      Health Literacy Status.
AB  - Background: Technology-delivered interventions have the potential to improve
      diabetes self-care and glycemic control among adults with type 2 diabetes (T2D).
      However, patients who do not engage with interventions may not reap benefits, and
      there is little evidence on how engagement with mobile health interventions
      varies by health literacy status. Objective: This study explored how patients
      with limited health literacy engaged with and experienced Rapid
      Education/Encouragement and Communications for Health (REACH), a text messaging
      intervention designed to support the self-care adherence of disadvantaged
      patients with T2D. We recruited adults with T2D from federally qualified health
      centers and used mixed methods to examine (1) associations between users' health
      literacy status and their prior mobile phone use and their engagement with REACH
      and (2) similarities and differences in users' self-reported benefits by health
      literacy status. Methods: Participants (N = 55) completed a survey, including
      measures of health literacy and prior mobile phone use. For 2 weeks, participants
      experienced REACH, which included daily text messages promoting self-care and
      asking about medication adherence, and weekly text messages providing medication
      adherence feedback. After 2 weeks, participants completed a semi-structured
      telephone interview about their experiences. Key Results: Participants with
      limited health literacy were less likely to have used cell phones to access the
      Internet (48% vs. 90%, p = .001) or email (36% vs. 87%, p < .001), but equally as
      likely to have used text messaging and to respond to REACH text messages (p = .12
      and p = .40, respectively) compared to participants with adequate health
      literacy. Participants responded to 93% of text messages on average and reported
      benefits of the intervention, including reminders and accountability, convenience
      and accessibility, and information and motivation. Participants with limited
      health literacy described a unique benefit of receiving social support from the
      intervention. Conclusions: Text messaging interventions may engage and benefit
      patients with T2D, regardless of health literacy status. Text messaging may have
      the potential to reduce T2D health disparities related to limited health
      literacy.

PMID- 29214243
TI  - Intracellular investigation on the differential effects of 4 polyphenols on MCF-7
      breast cancer cells by Raman imaging.
AB  - The past decades have seen significant interest in the study of polyphenolic
      compounds as potential therapeutic agents in medicine because they display a vast
      array of cellular effects beneficial to treat or manage a plethora of chronic
      diseases including inflammatory diseases, cardiovascular abnormalities and
      several types of cancer. These compounds act at different stages of
      carcinogenesis but deciphering their mode of action is a complex task. Live MCF-7
      breast cancer cells were investigated using Raman imaging to evaluate the
      perturbations induced after incubating cells with four different polyphenols:
      EGCG, gallic acid, resveratrol and tannic acid. First, clear spectral changes
      could be observed between the spectra of the cytoplasm and the nucleus of live
      MCF-7 cancer cells demonstrating a difference in their respective global chemical
      composition. The treatments induced significant modifications in the cells but no
      clear common pattern of modifications from the 4 drugs could be observed in the
      cell spectra in the 1800-600 cm-1 region. The high spatial resolution of Raman
      confocal microscopy enabled both the nucleus and cytoplasm to be independently
      targeted to study the impact of the polyphenols on the cell line. Positive
      spectral variations at 2851 cm-1 and 2920 cm-1 as well as in the 1460-1420 cm-1
      and 1660-1650 cm-1 spectral regions inside cell cytoplasm reflected an increase
      of the lipid content after exposure to polyphenols. Lipid accumulation appears to
      be an early biomarker of drug-induced cell stress and subsequent apoptosis.
      Interestingly an increase of cytochrome c into the cytosol was also induced by
      EGCG. These multiple events are possibly associated with cell apoptosis. In
      conclusion, Raman micro-spectroscopy provides a complementary spectroscopic
      method to realize biological investigations on live cancer cells and to evaluate
      the effects of polyphenols at the subcellular level.

PMID- 29214244
TI  - DNAzyme based visual detection of DNA methylation.
AB  - A novel colorimetric method which utilizes DNAzyme as a signal reporter was
      developed for DNA methylation detection. As low as 1/106 of methylated DNA could
      be successfully detected from unmethylated DNA. The discrimination ability is at
      least two orders of magnitude better than that of the methylation specific PCR.

PMID- 29214245
TI  - Enantioselective total synthesis of (-)-kainic acid and (+)-acromelic acid C via
      Rh(i)-catalyzed asymmetric enyne cycloisomerization.
AB  - A diversity-oriented synthetic strategy was developed for the total synthesis of
      kainoid amino acids, which led to the enantioselective synthesis of (-)-kainic
      acid and the first total synthesis of (+)-acromelic acid C. Rh(i)-catalyzed
      asymmetric enyne cycloisomerization served as the key reaction in this strategy
      for the rapid construction of highly functionalized lactam, and the resulting
      vinyl acetate moiety was further utilized as a versatile building block for the
      installation of both isopropylidene and 2-pyridone units existing in natural
      kainoids.

PMID- 29214247
TI  - Isomeric control of the mechanical properties of supramolecular filament
      hydrogels.
AB  - Supramolecular filament hydrogels are an emerging class of biomaterials that hold
      great promise for regenerative medicine, tissue engineering, and drug delivery.
      However, fine-tuning of their bulk mechanical properties at the molecular level
      without altering their network structures remains a significant challenge. Here
      we report an isomeric strategy to construct amphiphilic peptides through the
      conjugation of isomeric hydrocarbons to influence the local viscoelastic
      properties of their resulting supramolecular hydrogels. In this case, the packing
      requirements of the chosen isomeric hydrocarbons within the supramolecular
      filaments are dictated by their atomic arrangements at the molecular and
      intermolecular levels. Atomistic molecular dynamics simulations suggest that this
      design strategy can subtly alter the molecular packing at the interface between
      the peptide domain and the hydrophobic core of the supramolecular assemblies,
      without changing both the filament width and morphology. Our results from wide
      angle X-ray scattering and molecular simulations further confirm that alterations
      to the intermolecular packing at the interface impact the strength and degree of
      hydrogen bonding within the peptide domains. This subtle difference in the
      isomeric hydrocarbon design and their consequent packing difference led to
      variations in the persistence length of the individual supramolecular filaments.
      Microrheological analysis reveals that this difference in filament stiffness
      enables the fine-tuning of the mechanical properties of the hydrogel at the
      macroscopic scale. We believe that this isomeric platform provides an innovative
      method to tune the local viscoelastic properties of supramolecular polymeric
      hydrogels without necessarily altering their network structures.

PMID- 29214248
TI  - Rh(iii)-Catalyzed ortho-C-H alkynylation of N-phenoxyacetamides with hypervalent
      iodine-alkyne reagents at room temperature.
AB  - A Rh(iii)-catalyzed C-H alkynylation of substituted N-phenoxyacetamides has been
      developed with the aid of hypervalent iodine-alkyne reagents. Complementary to
      the Sonogashira coupling reaction, this protocol provides an efficient and
      straightforward method to access aryl alkynes at room temperature. The
      multifunctional directing group is preserved which can be further employed for
      ortho-directed functionalizations to obtain additional new complex products.

PMID- 29214249
TI  - Shapes matter: examining the optical response evolution in stretched aluminium
      nanoparticles via time-dependent density functional theory.
AB  - Using first-principles time-dependent density functional theory calculations, we
      investigate the shape-anisotropy effects on the optical response of a spherical
      aluminium nanoparticle subjected to a stretching process in different directions.
      Progressively increased stretching in one direction resulted in prolate spheroid
      (nanorice) geometries and produced a couple of well-distinguishable dominant
      peaks together with some satellite peaks in the UV-visible region of the
      electromagnetic spectrum. On the other hand, progressively increased stretching
      in two directions caused multiple peaks to appear in the UV-visible region of the
      electromagnetic spectrum. We believe that our findings can be beneficial for the
      emerging and potentially far-reaching field of aluminum plasmonics.

PMID- 29214250
TI  - Observations of a streak texture in the hybrid-aligned smectic-C phase.
AB  - A novel structure was observed below the smectic-A-smectic-C phase transition in
      a very thin open cell having an air interface above and enforced planar anchoring
      at the substrate below. The structure appears as periodic dark and light streaks
      running perpendicular to the oily streaks, which are present in the smectic-A
      phase [D. Coursault et al., Soft Matter, 2016, 12, 678]. These new streaks, which
      we call "soapy streaks", form by extending from one oily streak to the next in
      discrete steps, eliminating optical evidence at visible wavelengths of the oily
      streaks. At lower temperatures the streaks can undulate and exhibit a sawtooth
      like structure; such a structure is chiral in two dimensions. A possible scenario
      for the origin of these streaks is presented.

PMID- 29214251
TI  - Photoresponsive spherical nucleic acid: spatiotemporal control of the assembly
      circuit and intracellular microRNA release.
AB  - Herein, we designed and prepared a photoresponsive spherical nucleic acid (SNA)
      conjugate by inserting a photocleavable linker into the recognition sequence of
      SNA which can block the reactivity of the system temporally until specific UV
      light (~365 nm) is introduced. The photoresponsive SNA realizes temporal
      regulation of a self-assembly reaction circuit and spatial selectivity of
      microRNA release in a cell population, respectively.

PMID- 29214253
TI  - Velocity force curves, laning, and jamming for oppositely driven disk systems.
AB  - Using simulations we examine a two-dimensional disk system in which two disk
      species are driven in opposite directions. We measure the average velocity of one
      of the species versus the applied driving force and identify four phases as
      function of drive and disk density: a jammed state, a completely phase separated
      state, a continuously mixing phase, and a laning phase. The transitions between
      these phases are correlated with jumps in the velocity-force curves that are
      similar to the behavior observed at dynamical phase transitions in driven
      particle systems with quenched disorder such as vortices in type-II
      superconductors. In some cases the transitions between phases are associated with
      negative differential mobility in which the average absolute velocity of either
      species decreases with increasing drive. We also consider the situation where the
      drive is applied to only one species as well as systems in which both species are
      driven in the same direction with different drive amplitudes. We show that the
      phases are robust against the addition of thermal fluctuations. Finally, we
      discuss how the transitions we observe could be related to absorbing phase
      transitions where a system in a phase separated or laning regime organizes to a
      state in which contacts between the disks no longer occur and dynamical
      fluctuations are lost.

PMID- 29214255
TI  - A green-light-emitting, spontaneously blinking fluorophore based on
      intramolecular spirocyclization for dual-colour super-resolution imaging.
AB  - We have developed the first green-light-emitting, spontaneously blinking
      fluorophore (SBF), HEtetTFER. In combination with our near-infrared-light
      emitting SBF (HMSiR), HEtetTFER allows dual-colour single-molecule localization
      microscopy (SMLM) in buffer solution without any additive and without
      photoactivation.

PMID- 29214256
TI  - Thermally reversible nanoparticle gels with tuneable porosity showing structural
      colour.
AB  - We present colloidal gels formed from dispersions of PEG- and PEG+DNA-coated
      silica nanoparticles showing structural colour. The PEG- and PEG+DNA-coated
      silica colloids are functionalized using exclusively covalent bonds in aqueous
      conditions. Both sets of colloids self-assemble into thermally-reversible
      colloidal gels with porosity that can be tuned by changing the colloid volume
      fraction, although the interaction potentials of the colloids in the two systems
      are different. Confocal microscopy and image analysis tools are used to
      characteraize the gels' microstructures. Optical reflection spectroscopy is
      employed to study the underlying gel nanostructure and to characterize the
      optical response of the gels. X-ray nanotomography is used to visualize the
      nanoscale phase separation between the colloid-rich gel branches and the colloid
      free gel pores. These nanoparticle gels open new routes for creating structural
      colour where the gel structure is decoupled from the form factor of the
      individual colloids. This approach can be extended to create unexplored three
      dimensional macroscale materials with length scales spanning hundreds of
      nanometers, which has been difficult to achieve using other methods.

PMID- 29214258
TI  - Well-ordered self-assembled nanostructures of block copolymer films via
      synergistic integration of chemoepitaxy and zone annealing.
AB  - It is an extremely challenging task to fabricate macroscopically well-ordered
      nanostructures of block copolymers in a limited annealing time. In this work, we
      propose a novel integrated strategy of chemoepitaxy and zone annealing to direct
      the self-assembly of lamella-forming block copolymers. Large-scale numerical
      simulations corroborate that the integrated strategy has the capability to
      generate well-aligned and well-oriented lamellae over a macroscopic area via the
      synergy between the alignment guidance of the chemical template and the defect
      annihilation of zone annealing, even though the guiding stripes of the chemical
      template are extremely sparse. It is further demonstrated that the effective
      annealing time to achieve the well-ordered nanostructures is strongly dependent
      upon the pitch of guiding stripes and the thickness of block copolymer films.
      This work provides an instructive example for boosting the directing efficiency
      of chemoepitaxy through the integrated strategy, and lays the groundwork for
      rapidly fabricating well-ordered nanostructures of block copolymer
      nanolithography.

PMID- 29214257
TI  - Piceatannol attenuates behavioral disorder and neurological deficits in aging
      mice via activating the Nrf2 pathway.
AB  - Aging is a complex process that is accompanied by neurological damage. Chronic
      injection of d-galactose (d-gal) can accelerate the aging process similar to
      natural aging and is commonly used to build an aging model to investigate aging.
      In the present study, the effects of piceatannol on d-gal-induced aging in mice
      were evaluated. Piceatannol treatment showed an observable anti-aging effect.
      Results obtained in vivo showed that piceatannol retained spontaneous motor
      activity and enhanced spatial learning and memory abilities in mice in which
      aging was induced by d-gal. Morphometric analysis displayed that piceatannol
      prevented d-gal-induced neuronal loss, increased the number of Nissl bodies, and
      promoted cell proliferation in the hippocampus and cortex. Piceatannol also
      significantly decreased the level of MDA and elevated SOD and CAT activity in the
      hippocampal and cortical tissues. Furthermore, western blotting results revealed
      that piceatannol treatment noticeably reversed the suppression of Nrf2 nuclear
      translocation and increased the expressions of HO-1 and NOQ1 in mice with aging
      induced by d-gal. Furthermore, piceatannol activated the Nrf2 pathway in natural
      aging mice, whereas treatment with the Nrf2 inhibitor brusatol reversed the
      increased expressions of Nrf2, HO-1, and NOQ1. In conclusion, treatment with
      piceatannol ameliorates behavioral disorder and brain injury in an aging mouse
      model; this suggests that piceatannol is a promising pharmaceutical candidate for
      the treatment of age-associated diseases.

PMID- 29214259
TI  - Effect of surfactant tail length and ionic strength on the interfacial properties
      of nanoparticle-surfactant complexes.
AB  - Mixed nanoparticle-surfactant systems are effective foam stabilizing agents, but
      the lack of colloidal stability of the bulk dispersions makes interfacial
      characterization challenging. This study investigates the adsorption of
      CnTAB/SiO2 complexes at air/water interfaces through surface tension and
      interfacial rheology measurements. The effects of surfactant tail length, ionic
      strength, and interfacial processing on the surface properties are measured
      utilizing a bulk reservoir exchange methodology to avoid bulk destabilization.
      The surfactant structure controls the surface tension of the system, but has
      minimal impact on particle surface coverage or interfacial mechanics. Once
      adsorbed, nanoparticles remain pinned at the surface, while the surfactant is
      able to desorb upon bulk exchange with deionized water. Particle packing on the
      interface governs the interfacial mechanics, which can be modified by increasing
      the ionic strength of the bulk solution. Fully rigid interfaces can be generated
      at low particle coverages by controlling the ionic strength and interfacial
      processing. These findings contribute to the understanding of mixed particle
      surfactant systems and inform formulation and process design to achieve the
      desired interfacial mechanical properties.

PMID- 29214264
TI  - From E to Z and back again: reversible photoisomerisation of an isolated charge
      tagged azobenzene.
AB  - Substituted azobenzenes serve as chromophores and actuators in a wide range of
      molecular photoswitches. Here, tandem ion mobility spectrometry coupled with
      laser excitation is used to investigate the photoisomerisation of selected E and
      Z isomers of the charge-tagged azobenzene, methyl orange. Both isomers display a
      weak S1(npi*) photoisomerisation response in the blue part of the spectrum
      peaking at 440 nm and a more intense S2(pipi*) photoisomerisation response in the
      near-UV with maxima at 370 and 310 nm for the E and Z isomers, respectively. The
      60 nm separation between the S2(pipi*) photo-response maxima for the two isomers
      allows them to be separately addressed in the gas phase and to be reversibly
      photoisomerised using different colours of light. This is an essential
      characteristic of an ideal photoswitch. The study demonstrates that a sequence of
      light pulses at different stages in an ion mobility spectrometer can be deployed
      to generate and probe isomers that cannot be electrosprayed directly from
      solution or produced through collisions in the ion source.

PMID- 29214263
TI  - Contacts to solution-synthesized SnS nanoribbons: dependence of barrier height on
      metal work function.
AB  - Tin(ii) monosulfide (SnS) is a layered, anisotropic material that is of interest
      as a two-dimensional semiconductor for opto-electronic, thermoelectric, and
      piezoelectric applications. In this study, the effect of work function on contact
      behavior was investigated. Ni/Au, Pd/Au, Cr/Au, and Ti/Au contacts were
      fabricated onto individual, solution-synthesized, p-type SnS nanoribbons. The
      lower work function metals (Cr and Ti) formed Schottky contacts, whereas the
      higher work function metals (Ni and Pd) formed ohmic or semi-ohmic contacts. Of
      the ohmic contacts, Ni was found to have a lower contact resistance (~10-4 Omega
      cm2 or lower) than Pd (~10-3 Omega cm2 or lower). Both the calculated Schottky
      barriers (0.39 and 0.50 eV) for Cr and Ti, respectively, and the ohmic behavior
      for Ni and Pd agree with behavior predicted by Schottky-Mott theory. The results
      indicate that high work function metals should be considered to form low
      resistance contacts to SnS multilayers.

PMID- 29214268
TI  - Time-dependent transport characteristics of graphene tuned by ferroelectric
      polarization and interface charge trapping.
AB  - Graphene-based field effect transistors (FETs) were fabricated by employing
      ferroelectric Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) as a gate insulator. The co
      existing effects of ferroelectric gating and interface charge trapping on the
      transport properties of graphene were investigated with respect to the FET
      structure. The sheet resistance (Rs) of graphene shows a slight decay under a
      small applied voltage, which is much less than the coercive voltage of the
      ferroelectric PMN-PT, suggesting non-negligible charge trapping effects.
      Moreover, when the applied voltage is increased up to a value larger than the
      coercive voltage, Rs exhibits three states: an initial rapid change, followed by
      a slow nearly exponential evolution, and finally a saturated state either during
      the applied voltage is retained or after it is released. In particular, a high
      resistance state is finally reached due to the ferroelectric gating, implying
      that ferroelectric effects dominate this process. The underlying physical
      mechanism was fully investigated to effectively address the observed evolution of
      time-dependent Rs. Such a finding provides us an opportunity to understand the co
      existing effects of ferroelectric gating and charge trapping and tune the
      transport properties of graphene through the interface effects.

PMID- 29214269
TI  - Lab on a Chip in 2017.

PMID- 29214270
TI  - Protein separation under a microfluidic regime.
AB  - Lab-on-a-Chip (LoC), or micro-Total Analysis Systems (MUTAS), is recognized as a
      powerful analytical technology with high capabilities, though end-user products
      for protein purification are still far from being available on the market.
      Remarkable progress has been achieved in the separation of nucleic acids and
      proteins using electrophoretic microfluidic devices, while pintsize devices have
      been developed for protein isolation according to miniaturized chromatography
      principles (size, charge, affinity, etc.). In this work, we review the latest
      advances in the fabrication of components, detection methods and commercial
      implementation for the separation of biological macromolecules based on
      microfluidic systems, with some critical remarks on the perspectives of their
      future development towards standardized microfluidic systems and protocols. An
      outlook on the current needs and future applications is also presented.

PMID- 29214271
TI  - 3D time-dependent wave-packet approach in hyperspherical coordinates for the H +
      O2 reaction on the CHIPR and DMBE IV potential energy surfaces.
AB  - We perform quantum dynamics calculations for the reaction H + O2 -> O + OH on the
      ground-state potential energy surfaces CHIPR [Varandas, J. Chem. Phys., 2013,
      138, 134117] and DMBE IV [Pastrana et al., J. Phys. Chem. 1990, 94, 8073] using a
      three-dimensional time-dependent wave packet formalism based on hyperspherical
      coordinates. Initial rovibrational state [O2(v = 0-4, j = 1-5)] dependent
      reaction probabilities are calculated for the case J = 0. The J-shifting scheme
      is employed to estimate initial state selected integral cross-sections as well as
      thermal rate coefficients, which is verified using a realistic extrapolation
      scheme. The calculated total and state-to-state rate coefficients are compared
      with the findings of recent experimental studies and previous theoretical
      calculations.

PMID- 29214274
TI  - Radical mechanism of a nucleophilic reaction depending on a two-dimensional
      structure.
AB  - The mechanism of nucleophilic substitution deserves more investigation to include
      more reaction systems such as two-dimensional (2D) materials. In this study, we
      used fluorinated graphene (FG) as a representative 2D material to reveal the in
      depth mechanism of its defluorination and nucleophilic substitution reaction
      under attack of common nucleophiles to explore the chemistry of 2D materials and
      enrich the research on the nucleophilic substitution reaction. DFT calculations
      and electron paramagnetic resonance spectroscopy (EPR) demonstrated that
      defluorination of FG occurred via a radical mechanism after a single electron
      transfer (SET) reaction between the nucleophile and C-F bond, and a spin center
      was generated on the nanosheet and fluorine anion. Moreover, neither the SN1 nor
      SN2 mechanism was suggested to be appropriate for the substitution reaction of FG
      with a 2D structure due to the corresponding kinetics or thermodynamics
      disadvantage; hence, its nucleophilic substitution was proved to occur via a
      radical mechanism initiated by the defluorination step. The proposed substitution
      mechanism of FG demonstrates that nucleophilic substitution via a radical
      mechanism can also be applied to the attacking process of common nucleophiles
      without any particular conditions. Furthermore, it has been discovered that
      triethylamine without active hydrogen can be covalently attached to graphene
      nanosheets via a nucleophilic substitution reaction with FG; this further
      indicates a radical process for the nucleophilic substitution of FG rather than
      an SN1 or SN2 mechanism. The detailed process of the nucleophilic substitution
      reaction of FG was revealed to occur via a radical mechanism depending on the 2D
      structure of FG, which could also represent the typical characteristic of 2D
      chemistry.

PMID- 29214275
TI  - JPAD Is Moving Fast.

PMID- 29214276
TI  - MRI for Pre-Dementia Trials.

PMID- 29214277
TI  - Web-based Software for Real-time Simulation-assisted Trial Design in Alzheimer's
      Disease.
AB  - Clinical trials for Alzheimer's Disease (AD) are necessarily designed in the
      presence of substantial quantitative uncertainty. Certain important aspects of
      this uncertainty can be mitigated by developing longitudinal models for AD
      progression and by using these models to simulate virtual trials and estimate
      operating characteristics (such as statistical power, the probability of stopping
      at an interim analysis, the probability of identifying the correct dose, etc.) as
      a function of candidate design features, such as inclusion / exclusion criteria.
      In this brief report we describe the development and deployment of a customized
      software solution that allows such simulation-based results to be generated "on
      the fly" in the context of a drug development team meeting. This solution
      leverages a number of recent practical advances in statistical and scientific
      computing that could be much more broadly leveraged to assure more quantitatively
      grounded trial designs in Alzheimer's Disease.

PMID- 29214279
TI  - Bridging the Gap between Research and Clinical Practice in Asymptomatic
      Alzheimer's Disease.
AB  - Due to the growing global health impact of Alzheimer's disease (AD), there is a
      greater need for interventions that prevent or delay the onset of clinical
      symptoms of this debilitating disease. Clinical trials for disease-modifying
      compounds in AD have shifted towards earlier stages in the spectrum of illness,
      including the stage prior to cognitive symptoms. A population of specific
      interest for clinical research includes individuals with evidence of Alzheimer's
      disease pathology who are asymptomatic (ADPa). The challenges and barriers
      regarding medical treatment of ADPa must be identified and addressed prior to the
      completion of a positive clinical trial in order to accelerate the translation of
      research findings to clinical practice. This report applies an existing public
      health impact model from Spencer and colleagues (2013) to evaluate the readiness
      of the clinical practice environment to treat ADPa individuals if a disease
      modifying agent achieves approval. We contrast the current clinical practice
      environment with a potential future state through investigating the
      effectiveness, reach, feasibility, sustainability, and transferability of the
      practice of treating ADPa individuals.

PMID- 29214278
TI  - Ginkgetin Ameliorates Neuropathological Changes in APP/PS1 Transgenical Mice
      Model.
AB  - The extracellular accumulation of amyloid beta protein (Abeta), reactive gliosis
      and cerebral amyloid angiopathy (CAA) play critical roles in the pathogenesis of
      Alzheimer's disease (AD). Ginkgetin, a biflavone isolated from Ginkgo biloba
      leaves, was previously reported to exhibit strong neuroprotection against
      cytotoxic insults induced by oxidative stress and amyloid beta, but it remains
      unclear whether ginkgetin has therapeutic effect on Alzheimer's disease (AD) in
      vivo. In the present study, we investigated 9 months treatment effects of
      ginkgetin diet in APP/PS1 mice. Our results show that ginkgetin can significantly
      reduce plasma Abeta levels 59% and Abeta plaque 51% in the brain of APP/PS1
      transgenic mice (P<0.05), effectively inhibits cerebral microhemorrhage 69%
      (P<0.05), significantly decreases astrogliosis 50% and ameliorate inflammation
      (P<0.05), exhibits several biological properties for AD.

PMID- 29214280
TI  - Vitamin D and Dementia.
AB  - Emerging evidence suggests that low vitamin D concentrations are potentially
      involved in the pathogenesis of dementia. This is of particular interest when
      considering the high prevalence of vitamin D deficiency in elderly adults and the
      urgent need to identify modifiable risk factors for dementia. Studies have found
      that vitamin D is implicated in procognitive and neuroprotective functions,
      including the reduction of Alzheimer's disease hallmarks such as amyloid beta and
      phosphorylated tau. Cross-sectional studies have consistently found that vitamin
      D concentrations are significantly lower in individuals with Alzheimer's disease
      and cognitive impairment compared to healthy controls. Longitudinal studies
      support an association between low vitamin D concentrations and an increased risk
      of dementia and cognitive decline. Neuroimaging studies are beginning to uncover
      the potential neurodegenerative and cerebrovascular mechanisms that underlie
      these associations such as white matter hyperintensities and enlarged ventricular
      volume, although there is currently a lack of longitudinal studies. In contrast
      to observational studies, findings from interventional studies have produced
      mixed results on the benefits of vitamin D supplementation on dementia and
      cognitive outcomes. Interpretation of the findings from these studies is hampered
      by several major methodological limitations, such as small sample sizes,
      inadequate doses and inclusion of participants unlikely to benefit from vitamin D
      supplementation. There is a need for large double-blind randomised-control trials
      investigating whether vitamin D supplementation can halt or delay the risk of
      dementia-related outcomes in individuals with low vitamin D concentrations.

PMID- 29214282
TI  - Error in Figure 3.

PMID- 29214281
TI  - Equivalence? Clarifications Required.

PMID- 29214283
TI  - Equivalence? Clarifications Required-Reply.

PMID- 29214285
TI  - Corrected MNI Coordinates in a Table and 2 Figures.

PMID- 29214284
TI  - Characteristics of Medical Liability Claims Against Dermatologists From 1991
      Through 2015.
AB  - Importance: Recognizing malpractice trends in the field of dermatology is
      important for establishing safeguards for patient care and minimizing liability.
      However, there is a lack of published data on malpractice claims against
      dermatologists. Objective: To determine characteristics of medical professional
      liability claims in the field of dermatology and to compare these claims with
      those against all physicians. Design, Setting, and Participants: We examined
      malpractice liability data collected on dermatologists and other physicians
      insured by companies that report data to the Physician Insurers Association of
      America Data Sharing Project (PIAA-DSP), a nationally representative liability
      claims registry. Data analyzed spanned the years 1991 through 2015. Main Outcomes
      and Measures: Demographic characteristics of dermatologists subject to claims,
      characteristics of closed claims, medical errors associated with closed claims,
      and patient outcomes leading to closed claims. Results: Data on a total of 90 743
      closed claims were analyzed, 1084 (1.2%) against dermatologists and 89 659
      (98.8%) against nondermatologists. More lawsuits were brought against male (n =
      753, 69.5%) than female dermatologists (n = 270, 24.9%); 5.6% of claims (n = 61)
      did not identify the physician's sex. Full-time practitioners (n = 1035, 95.5%)
      and those in solo practice (n = 600, 55.4%) were more likely to be sued than
      those in group practices (n = 429, 39.6%) and institutions (n = 31, 2.9%). Most
      claims against dermatologists were abandoned, withdrawn, or dismissed (n = 735,
      67.8%). Between 2006 and 2015, trial verdicts favoring defendants exceeded trial
      verdicts favoring plaintiffs by a factor of 7. Errors that occurred during a
      procedure spawned the most claims (n = 305), of which 102 were paid. Misdiagnoses
      comprised the second-highest number of claims (n = 192), of which 62 were paid.
      The average recovery per claim was $238 145. The most common procedure leading to
      claims was skin operations (420 claims, of which 130 were paid). The most common
      adverse patient outcome associated with claims was dyschromia, resulting in 171
      claims, of which 40 were paid. Conclusions and Relevance: Male dermatologists
      were sued more often than female dermatologists. Overall, alleged errors in
      procedures and misdiagnosis gave rise to the most lawsuits. Dyschromia was the
      most common adverse outcome alleged in lawsuits.

PMID- 29214286
TI  - Errors in Table 1.

PMID- 29214287
TI  - Optical Coherence Tomography Features of Dermatophytoma.

PMID- 29214288
TI  - Putting Psychosis Into Sociocultural Context: An International Study in 17
      Locations.

PMID- 29214290
TI  - Association of Immunotherapy With Overall Survival in Elderly Patients With
      Melanoma.
AB  - Importance: Melanoma treatment has been revolutionized with the development of
      immune-based therapies that offer durable clinical responses in a subset of
      patients. Clinical outcomes after treatment by immunotherapy can be influenced by
      the host's immune system. The immune system is modified with age by age-related
      immune dysfunction. Objective: To evaluate if age influences clinical outcome and
      immune adverse events in patients treated by immunotherapy for metastatic
      melanoma. Design, Setting, and Participants: This was a single-center cohort
      analysis in patients treated with immunotherapy for metastatic melanoma between
      January 2007 and February 2016, in the Lyon Sud Hospital, France. A total of 92
      patients with metastatic melanoma treated with ipilimumab, nivolumab, or
      pembrolizumab were retrospectively analyzed. Main Outcomes and Measures: Overall
      survival, progression-free survival, and immune-related adverse events were
      evaluated for each treatment line according to the patients' age. Results: A
      total of 92 patients were eligible and included in this study for a total of 120
      lines of treatment. Fifty-four patients were included in the cohort that was 65
      years or younger (24 [44%] were female; mean [SD] age, 48.1 [12.5] years), and 38
      patients were included in the cohort that was older than 65 years (12 [34%] were
      female; mean [SD] age, 74.8 [6.9] years). Mean follow-up duration starting at
      treatment initiation was 12.5 months. Patients older than 65 years treated with
      immunotherapy had a better mean progression-free survival (4.8 vs 3.4 months; P =
      .04) and overall survival (not reached vs 10.1 months; P = .009) than younger
      patients in univariate analysis, and after adjusting on prognosis covariates.
      This was particularly true with patients treated with anti-programmed cell death
      protein 1. Common immune-related adverse effects were similar in both cohorts.
      Conclusions and Relevance: Age might be associated with a better clinical outcome
      after treatment with immunotherapy in the real-life setting. In our cohort, older
      patients did not have more immune-related adverse events. Further studies are
      warranted to confirm our results and describe the underlying mechanisms involved.

PMID- 29214289
TI  - Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study.
AB  - Importance: Psychotic disorders contribute significantly to the global disease
      burden, yet the latest international incidence study of psychotic disorders was
      conducted in the 1980s. Objectives: To estimate the incidence of psychotic
      disorders using comparable methods across 17 catchment areas in 6 countries and
      to examine the variance between catchment areas by putative environmental risk
      factors. Design, Setting, and Participants: An international multisite incidence
      study (the European Network of National Schizophrenia Networks Studying Gene
      Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among
      2774 individuals from England (2 catchment areas), France (3 catchment areas),
      Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6
      catchment areas), and Brazil (1 catchment area) with a first episode of
      nonorganic psychotic disorders (International Statistical Classification of
      Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33)
      confirmed by the Operational Criteria Checklist. Denominator populations were
      estimated using official national statistics. Exposures: Age, sex, and
      racial/ethnic minority status were treated as a priori confounders. Latitude,
      population density, percentage unemployment, owner-occupied housing, and single
      person households were treated as catchment area-level exposures. Main Outcomes
      and Measures: Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33),
      nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10
      codes F30-F33) confirmed by the Operational Criteria Checklist. Results: A total
      of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile
      range, 23.0-41.0 years]) with incident cases of psychotic disorders were
      identified during 12.9 million person-years at risk (crude incidence, 21.4 per
      100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of
      2183 patients (78.7%) had nonaffective psychotic disorders. After direct
      standardization for age, sex, and racial/ethnic minority status, an 8-fold
      variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI,
      3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0)
      per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic
      minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for
      men 18 to 24 years of age, and were lower in catchment areas with more owner
      occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns
      were observed for nonaffective psychoses; a lower incidence of affective
      psychoses was associated with higher area-level unemployment (incidence rate
      ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance: This study confirmed
      marked heterogeneity in risk for psychotic disorders by person and place,
      including higher rates in younger men, racial/ethnic minorities, and areas
      characterized by a lower percentage of owner-occupied houses.

PMID- 29214291
TI  - Effects of International Electrocardiographic Interpretation Recommendations on
      African American Athletes.

PMID- 29214292
TI  - Occult Carbon Monoxide Poisoning-Reply.

PMID- 29214293
TI  - Elevated CK-MB With Normal Total Creatine Kinase Levels in Patients Undergoing
      Maintenance Hemodialysis-Reply.

PMID- 29214298
TI  - Improving Hairdressers' Knowledge and Self-efficacy to Detect Scalp and Neck
      Melanoma by Use of an Educational Video.

PMID- 29214299
TI  - Abdominal Handlebar Injury.

PMID- 29214300
TI  - The Reality of Long-term Follow-up of Bariatric/Metabolic Surgery Patients-A
      Conundrum.

PMID- 29214301
TI  - Practicing Safe Dermatology-Screening Out Liability.

PMID- 29214304
TI  - Timing of Continuous Renal Replacement Therapy.

PMID- 29214305
TI  - Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in
      Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the
      SAVOR-TIMI 53 Trial.
AB  - Importance: An elevated level of urinary albumin to creatinine ratio (UACR) is a
      marker of renal dysfunction and predictor of kidney failure/death in patients
      with type 2 diabetes. The prognostic use of UACR in established cardiac
      biomarkers is not well described. Objective: To evaluate whether UACR offers
      incremental prognostic benefit beyond risk factors and established plasma
      cardiovascular biomarkers. Design, Setting, and Participants: The Saxagliptin
      Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus
      Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 study was performed from
      May 2010 to May 2013 and evaluated the safety of saxagliptin vs placebo in
      patients with type 2 diabetes with overt cardiovascular disease or multiple risk
      factors. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years).
      Interventions: Patients were randomized to saxagliptin vs placebo plus standard
      care. Main Outcomes and Measures: Baseline UACR was measured in 15 760 patients
      (95.6% of the trial population) and categorized into thresholds. Results: Of 15
      760 patients, 5205 were female (33.0%). The distribution of UARC categories were:
      5805 patients (36.8%) less than 10 mg/g, 3891 patients (24.7%) at 10 to 30 mg/g,
      4426 patients (28.1%) at 30 to 300 mg/g, and 1638 patients (10.4%) at more than
      300 mg/g. When evaluated without cardiac biomarkers, there was a stepwise
      increase with each higher UACR category in the incidence of the primary composite
      end point (cardiovascular death, myocardial infarction, or ischemic stroke)
      (3.9%, 6.9%, 9.2%, and 14.3%); cardiovascular death (1.4%, 2.6%, 4.1%, and 6.9%);
      and hospitalization for heart failure (1.5%, 2.5%, 4.0%, and 8.3%) (adjusted P <
      .001 for trend). The net reclassification improvement at the event rate for each
      end point was 0.081 (95% CI, 0.025 to 0.161), 0.129 (95% CI, 0.029 to 0.202), and
      0.056 (95% CI, -0.005 to 0.141), respectively. The stepwise increased
      cardiovascular risk associated with a UACR of more than 10 mg/g was also present
      within each chronic kidney disease category. The UACR was associated with
      outcomes after including cardiac biomarkers. However, the improvement in
      discrimination and reclassification was attenuated; net reclassification
      improvement at the event rate was 0.022 (95% CI, -0.022 to 0.067), -0.008 (-0.034
      to 0.053), and 0.043 (-0.030 to 0.052) for the primary end point, cardiovascular
      death, and hospitalization for heart failure, respectively. Conclusions and
      Relevance: In patients with type 2 diabetes, UACR was independently associated
      with increased risk for a spectrum of adverse cardiovascular outcomes. However,
      the incremental cardiovascular prognostic value of UACR was minimal when
      evaluated together with contemporary cardiac biomarkers. Trial Registration:
      clinicaltrials.gov Identifier: NCT01107886.

PMID- 29214306
TI  - Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment
      of Bariatric Surgery (LABS) Study.
AB  - Importance: More information is needed about the durability of weight loss and
      health improvements after bariatric surgical procedures. Objective: To examine
      long-term weight change and health status following Roux-en-Y gastric bypass
      (RYGB) and laparoscopic adjustable gastric banding (LAGB). Design, Setting, and
      Participants: The Longitudinal Assessment of Bariatric Surgery (LABS) study is a
      multicenter observational cohort study at 10 US hospitals in 6 geographically
      diverse clinical centers. Adults undergoing bariatric surgical procedures as part
      of clinical care between 2006 and 2009 were recruited and followed up until
      January 31, 2015. Participants completed presurgery, 6-month, and annual research
      assessments for up to 7 years. Main Outcome and Measures: Percentage of weight
      change from baseline, diabetes, dyslipidemia, and hypertension, determined by
      physical measures, laboratory testing, and medication use. Results: Of 2348
      participants, 1738 underwent RYGB (74%) and 610 underwent LAGB (26%). For RYBG,
      the median age was 45 years (range, 19-75 years), the median body mass index
      (calculated as weight in kilograms divided by height in meters squared) was 47
      (range, 34-81), 1389 participants (80%) were women, and 257 participants (15%)
      were nonwhite. For LAGB, the median age was 48 years (range, 18-78), the body
      mass index was 44 (range, 33-87), 465 participants (76%) were women, and 63
      participants (10%) were nonwhite. Follow-up weights were obtained in 1300 of 1569
      (83%) eligible for a year-7 visit. Seven years following RYGB, mean weight loss
      was 38.2 kg (95% CI, 36.9-39.5), or 28.4% (95% CI, 27.6-29.2) of baseline weight;
      between years 3 and 7 mean weight regain was 3.9% (95% CI, 3.4-4.4) of baseline
      weight. Seven years after LAGB, mean weight loss was 18.8 kg (95% CI, 16.3-21.3)
      or 14.9% (95% CI, 13.1-16.7), with 1.4% (95% CI, 0.4-2.4) regain. Six distinct
      weight change trajectory patterns for RYGB and 7 for LAGB were identified. Most
      participants followed trajectories in which weight regain from 3 to 7 years was
      small relative to year-3 weight loss, but patterns were variable. Compared with
      baseline, dyslipidemia prevalence was lower 7 years following both procedures;
      diabetes and hypertension prevalence were lower following RYGB only. Among those
      with diabetes at baseline (488 of 1723 with RYGB [28%]; 175 of 604 with LAGB
      [29%]), the proportion in remission at 1, 3, 5, and 7 years were 71.2% (95% CI,
      67.0-75.4), 69.4% (95% CI, 65.0-73.8), 64.6% (95% CI, 60.0-69.2), and 60.2% (95%
      CI, 54.7-65.6), respectively, for RYGB and 30.7% (95% CI, 22.8-38.7), 29.3% (95%
      CI, 21.6-37.1), 29.2% (95% CI, 21.0-37.4), and 20.3% (95% CI, 9.7-30.9) for LAGB.
      The incidence of diabetes at all follow-up assessments was less than 1.5% for
      RYGB. Bariatric reoperations occurred in 14 RYGB and 160 LAGB participants.
      Conclusions and Relevance: Following bariatric surgery, different weight loss
      patterns were observed, but most participants maintained much of their weight
      loss with variable fluctuations over the long term. There was some decline in
      diabetes remission over time, but the incidence of new cases is low following
      RYGB. Trial Registration: clinicaltrials.gov Identifier: NCT00465829.

PMID- 29214308
TI  - Interpretation of the ATHENA Trial-Caveats and Future Directions.

PMID- 29214307
TI  - Single-Word Speech Intelligibility in Children and Adults With Down Syndrome.
AB  - Purpose: A single-word identification test was used to study speech production in
      children and adults with Down syndrome (DS) to determine the developmental
      pattern of speech intelligibility with an emphasis on vowels. Method: Speech
      recordings were collected from 62 participants with DS aged 4-40 years and 25
      typically developing participants aged 4-7 years. Panels of 5 adult lay listeners
      transcribed the speech recordings orthographically, and their responses were
      scored in comparison with the speakers' target words. Results: Speech
      intelligibility in persons with DS improved with age, especially between the ages
      of 4 and 16 years. Whereas consonants contribute to intelligibility, vowels also
      played an important role in reduced intelligibility with an apparent
      developmental difference in low versus high vowels, where the vowels /ae/
      and/alpha/ developed at a later age than /i/ and /u/. Interspeaker variability
      was large, with male individuals being generally less intelligible than female
      individuals and some adult men having very low intelligibility. Conclusion:
      Results show age-related patterns in speech intelligibility in persons with DS
      and identify the contribution of dimensions of vowel production to
      intelligibility. The methods used clarify the phonetic basis of reduced
      intelligibility, with implications for assessment and treatment.

PMID- 29214309
TI  - Emergency Department Opioid Misuse Diagnoses Increasing in Adolescents and Young
      Adults.

PMID- 29214310
TI  - Tear Levels of Insulin-Like Growth Factor Binding Protein 3 Correlate With
      Subbasal Nerve Plexus Changes in Patients With Type 2 Diabetes Mellitus.
AB  - Purpose: This study investigated the expression of insulin-like growth factor
      binding protein-3 (IGFBP-3) in basal tears of patients with type 2 diabetes
      mellitus compared to nondiabetic controls; and correlated tear levels of IGFBP-3
      with morphologic changes in the subbasal nerve plexus and density of basal
      corneal epithelial cells. Methods: This was a single visit, cross-sectional
      study. Diabetic and control subjects were matched for age, sex, smoking status,
      and body mass index. Tear levels of IGFBP-3 were measured using ELISA. Corneal
      nerve and basal epithelial cell changes were measured using in vivo confocal
      microscopy. Results: Tear levels of IGFBP-3 were 3.5-fold higher in those with
      diabetes. Patients with diabetes also showed a reduction in nerve fiber layer,
      nerve branch density, and corneal basal epithelial cell density. There was no
      significant difference in corneal sensitivity. IGFBP-3 levels were highly
      correlated with nerve fiber length and branch density; while hemoglobin (Hb)A1c
      was only moderately correlated. There were no significant differences in the
      clinical or subjective signs of dry eye between groups, indicating that tear
      levels of IGFBP-3 and corneal nerve changes were not due to the presence of mild
      dry eye. Conclusions: These findings indicate that tear levels of IGFBP-3 are
      more tightly correlated to nerve fiber changes in diabetes than HbA1c. Future
      studies that stratify the severity of diabetic disease with tear levels of IGFBP
      3 are needed to validate this finding.

PMID- 29214311
TI  - Fingolimod Suppresses a Cascade of Core Vicious Cycle in Dry Eye NOD Mouse Model:
      Involvement of Sphingosine-1-Phosphate Receptors in Infiltrating Leukocytes.
AB  - Purpose: The purpose of this study was to evaluate the inhibitory mechanism of
      fingolimod and the involvement of sphingosine-1-phosphate receptors (S1PRs) and
      cytokines-matrix metalloproteinases (MMPs)/MAP kinases (MAPKs) signaling in a dry
      eye disease (DED) mouse model. Methods: Sixty-four male NOD mice (DED model) and
      16 age-matched BALB/c mice were used. In a preliminary experiment, 16 NOD mice
      were randomly divided into a positive control group and fingolimod-treated
      groups, with 8 BALB/c mice serving as wild-type control. In a subsequent,
      separate study, 48 NOD mice were randomly divided into 6 groups: fingolimod
      treated groups at three different concentrations (0.05%, 0.005%, and 0.001%),
      normal saline group, untreated group, and fingolimod+W146 group. Animals received
      normal saline or fingolimod eyedrops three times daily until euthanasia 2 months
      later. Mice in the fingolimod+W146 group received daily intraperitoneal
      injections of W146 (0.1 mg/kg/day). Proinflammatory mediators were assessed by a
      protein array. Activities of MMP-2 and MMP-9 were evaluated by zymography. MAPKs
      and S1PRs were examined by Western blots and immunohistochemistry. Infiltrating
      cells and inhibitory mechanisms were assessed. Results: In the positive control
      group, levels of inflammatory mediators and S1PRs were upregulated. By
      comparison, fingolimod treatment significantly suppressed such markers which were
      significantly reversed by W146 (P < 0.01). Importantly, by double
      immunofluorescence staining, leukocytes were confirmed involved in DED in the NOD
      mouse model. Conclusions: Leukocytes are involved in DED in the NOD mouse model.
      The therapeutic mechanisms of fingolimod may be associated with inhibitory roles
      of "cytokines-MMPs/MAPKs" cycle in NOD mouse ocular surface tissues by mediating
      S1PRs in infiltrating leukocytes.

PMID- 29214312
TI  - Transretinal ERG in Studying Mouse Rod Phototransduction: Comparison With Local
      ERG Across the Rod Outer Segments.
AB  - Purpose: Electroretinography (ERG) is the gold standard in clinical examinations
      of retinal function. Corneal ERG is widely used for diagnostics, but ERG
      components from the inner retina complicate quantitative investigations of the
      phototransduction cascade. Transretinal ERG (TERG) recorded ex vivo enables
      pharmacologic isolation of signals generated by photoreceptor cells, establishing
      an appealing electrophysiologic method for diverse studies of phototransduction.
      Pharmacologically isolated TERG, however, contains components arising in the
      photoreceptor inner segments. Here, we compared simultaneously recorded TERG and
      local ERG across the outer segment layer (LERG-OS) to determine how consistently
      TERG reflects changes in the rod outer segment current signaling. Methods:
      Recordings were made from dark-adapted, isolated C57BL/6J mouse retinas
      superfused with HEPES or bicarbonate buffered solution containing 2-mM aspartate
      or 20-MUM DL-2-amino-4-phosphonobutyric acid to block synaptic transmission, and
      50-MUM BaCl2 to block the Muller cell component. TERG responses were recorded
      with macroelectrodes on both sides of the retina while responses across different
      retinal layers were recorded with microelectrodes. Results: The time-to-peak and
      the dominant time constant values were slightly smaller and the half-saturating
      stimulus was somewhat stronger in TERG compared with LERG-OS. No differences in
      light adaptation data were observed between the methods. LERG responses recorded
      across the whole photoreceptor layer were similar to those by TERG. Conclusions:
      TERG photoreceptor responses correspond well with the LERG-OS responses. The main
      differences are the nose component and slightly faster response kinetics observed
      by TERG. We conclude that TERG can be used for reliable quantitative
      investigation of phototransduction.

PMID- 29214314
TI  - Quantitative Fundus Autofluorescence in Pseudoxanthoma Elasticum.
AB  - Purpose: To quantify lipofuscin-associated fundus autofluorescence in patients
      with pseudoxanthoma elasticum (PXE), a model disease for Bruch's membrane
      pathology. Methods: In this prospective, monocenter, cross-sectional case-control
      study, 49 patients with PXE (mean age: 46 years, range 18-62) underwent
      quantitative fundus autofluorescence (qAF) imaging with a modified scanning laser
      ophthalmoscope containing an internal fluorescent reference for normalization of
      images. The mean qAF values of a circular ring centered on the fovea (qAF8) were
      measured and compared to 108 healthy controls (mean age 40 years, range 18-64).
      Results: Overall, patients with PXE showed lower qAF8 values compared to controls
      (difference from controls -23%, 95% confidence interval [CI] -29% to -16%, P <
      0.001). The reduction was most pronounced in patients older than 40 years (-30%,
      95% CI -36% to -23%, P < 0.001) and was negatively correlated with the extent of
      Bruch's membrane calcification (r = -0.49, 95% CI: -0.67 to -0.22). The
      topographic distribution revealed a greater reduction of qAF values toward the
      optic disc than temporally compared to controls (P < 0.001). The phenotype of
      patients with reduced qAF values was characterized by pattern-dystrophy-like
      changes (71%; 10 of 14), reticular pseudodrusen (71%; 10 of 14) and limited areas
      of atrophy (29%, 4 of 14). Conclusions: Reduced qAF8 values are a characteristic
      finding in patients with PXE, indicating that Bruch's membrane disease may result
      in a modification of the accumulation, distribution, or composition (or a
      combination thereof) of lipofuscin in retinal pigment epithelial cells.

PMID- 29214315
TI  - Will the FDA's New Tobacco Strategy Be a Game Changer?

PMID- 29214313
TI  - RNA-Sequencing Gene Expression Profiling of Orbital Adipose-Derived Stem Cell
      Population Implicate HOX Genes and WNT Signaling Dysregulation in the
      Pathogenesis of Thyroid-Associated Orbitopathy.
AB  - Purpose: The purpose of this study was to characterize the intrinsic cellular
      properties of orbital adipose-derived stem cells (OASC) from patients with
      thyroid-associated orbitopathy (TAO) and healthy controls. Methods: Orbital
      adipose tissue was collected from a total of nine patients: four controls and
      five patients with TAO. Isolated OASC were characterized with mesenchymal stem
      cell-specific markers. Orbital adipose-derived stem cells were differentiated
      into three lineages: chondrocytes, osteocytes, and adipocytes. Reverse
      transcription PCR of genes involved in the adipogenesis, chondrogenesis, and
      osteogenesis pathways were selected to assay the differentiation capacities. RNA
      sequencing analysis (RNA-seq) was performed and results were compared to assess
      for differences in gene expression between TAO and controls. Selected top-ranked
      results were confirmed by RT-PCR. Results: Orbital adipose-derived stem cells
      isolated from orbital fat expressed high levels of mesenchymal stem cell markers,
      but low levels of the pluripotent stem cell markers. Orbital adipose-derived stem
      cells isolated from TAO patients exhibited an increase in adipogenesis, and a
      decrease in chondrogenesis and osteogenesis. RNA-seq disclosed 54 differentially
      expressed genes. In TAO OASC, expression of early neural crest progenitor marker
      (WNT signaling, ZIC genes and MSX2) was lost. Meanwhile, ectopic expression of
      HOXB2 and HOXB3 was found in the OASC from TAO. Conclusion: Our results suggest
      that there are intrinsic genetic and cellular differences in the OASC populations
      derived from TAO patients. The upregulation in adipogenesis in OASC of TAO may be
      is consistent with the clinical phenotype. Downregulation of early neural crest
      markers and ectopic expression of HOXB2 and HOXB3 in TAO OASC demonstrate
      dysregulation of developmental and tissue patterning pathways.

PMID- 29214316
TI  - Association Between Hospital Financial Distress and Immediate Breast
      Reconstruction Surgery After Mastectomy Among Women With Ductal Carcinoma In
      Situ.
AB  - Importance: Hospital financial distress (HFD) is a state in which a hospital is
      at risk of closure because of its financial condition. Hospital financial
      distress may reduce the services a hospital can offer, particularly unprofitable
      ones. Few studies have assessed the association of HFD with quality of care.
      Objective: To examine the association between HFD and receipt of immediate breast
      reconstruction surgery after mastectomy among women diagnosed with ductal
      carcinoma in situ (DCIS). Design, Setting, and Participants: This retrospective
      cohort study assessed data from the Nationwide Inpatient Sample of 5760 women
      older than 18 years (mean [SD] age: 57.5 [13.2]) with DCIS who underwent
      mastectomy in 2008-2012 at hospitals categorized by financial distress. Women
      treated at 1156 hospitals located in 538 different counties across Arkansas,
      Arizona, California, Colorado, Connecticut, Florida, Iowa, Kentucky,
      Massachusetts, Maryland, Missouri, North Carolina, New Hampshire, New Jersey,
      Nevada, New York, Oregon, Pennsylvania, Rhode Island, Utah, Virginia, Vermont,
      Washington, Wisconsin, West Virginia, and Wyoming were included. Of these, 2385
      women (41.4%) underwent immediate breast reconstruction surgery. Women with
      invasive cancer were excluded. The database included unique hospital
      identification variables, and participants were identified using International
      Classification of Diseases, Ninth Revision, Clinical Modification codes. Data
      were analyzed from January 1, 2012, to February 28, 2014. Main Outcomes and
      Measures: The primary outcome was the adjusted association between HFD and
      receipt of immediate breast reconstruction surgery after mastectomy. Results: In
      this analysis of database information, 2385 of 5760 women (41.4%) received
      immediate breast reconstruction surgery. Of these, 693 (36.7%) were treated at a
      hospital under high HFD and received immediate breast reconstruction surgery
      compared with 863 (44.0%) treated at a hospital under low HFD (P < .001).
      Reconstruction surgery was associated with younger age, white race, private
      insurance, treatment at a teaching and cancer hospital, private hospital
      ownership, and the percentage of individuals in the county with insurance. After
      adjustment, women treated at hospitals under high HFD (OR, 0.79; 95% CI, 0.62
      0.99) and medium HFD (OR, 0.76; 95% CI, 0.61-0.94) were significantly less likely
      to receive reconstruction than women treated at hospitals with low to no HFD.
      Conclusions and Relevance: The financial strength of the hospital where a patient
      receives treatment is associated with receipt of immediate breast reconstruction
      surgery. In addition to focusing on patient-related factors, efforts to improve
      quality should also focus on hospital-related factors.

PMID- 29214317
TI  - Connections Between Hospital Financial Distress, Physician Incentive, and Patient
      Access to Breast Reconstruction.

PMID- 29214318
TI  - Reduction in Opioid Prescribing Through Evidence-Based Prescribing Guidelines.

PMID- 29214319
TI  - Electrocardiographic Findings in National Basketball Association Athletes.
AB  - Importance: While it is known that long-term intensive athletic training is
      associated with cardiac structural changes that can be reflected on surface
      electrocardiograms (ECGs), there is a paucity of sport-specific ECG data. This
      study seeks to clarify the applicability of existing athlete ECG interpretation
      criteria to elite basketball players, an athlete group shown to develop
      significant athletic cardiac remodeling. Objective: To generate normative ECG
      data for National Basketball Association (NBA) athletes and to assess the
      accuracy of athlete ECG interpretation criteria in this population. Design,
      Setting, and Participants: The NBA has partnered with Columbia University Medical
      Center to annually perform a review of policy-mandated annual preseason ECGs and
      stress echocardiograms for all players and predraft participants. This
      observational study includes the preseason ECG examinations of NBA athletes who
      participated in the 2013-2014 and 2014-2015 seasons, plus all participants in the
      2014 and 2015 NBA predraft combines. Examinations were performed from July 2013
      to May 2015. Data analysis was performed between December 2015 and March 2017.
      Exposures: Active roster or draft status in the NBA and routine preseason ECGs
      and echocardiograms. Main Outcomes and Measures: Baseline quantitative ECG
      variables were measured and ECG data qualitatively analyzed using 3 existing,
      athlete-specific interpretation criteria: Seattle (2012), refined (2014), and
      international (2017). Abnormal ECG findings were compared with matched
      echocardiographic data. Results: Of 519 male athletes, 409 (78.8%) were African
      American, 96 (18.5%) were white, and the remaining 14 (2.7%) were of other
      races/ethnicities; 115 were predraft combine participants, and the remaining 404
      were on active rosters of NBA teams. The mean (SD) age was 24.8 (4.3) years.
      Physiologic, training-related changes were present in 462 (89.0%) athletes in the
      study. Under Seattle criteria, 131 (25.2%) had abnormal findings, compared with
      108 (20.8%) and 81 (15.6%) under refined and international criteria,
      respectively. Increased age and increased left ventricular relative wall
      thickness (RWT) on echocardiogram were highly associated with abnormal ECG
      classifications; 17 of 186 athletes (9.1%) in the youngest age group (age 18-22
      years) had abnormal ECGs compared with 36 of the 159 athletes (22.6%) in the
      oldest age group (age 27-39 years) (odds ratio, 2.9; 95% CI, 1.6-5.4; P < .001).
      Abnormal T-wave inversions (TWI) were present in 32 athletes (6.2%), and this was
      associated with smaller left ventricular cavity size and increased RWT. One of
      the 172 athletes (0.6%) in the lowest RWT group (range, 0.24-0.35) had TWIs
      compared with 24 of the 163 athletes (14.7%) in the highest RWT group (range,
      0.41-0.57) (odds ratio, 29.5; 95% CI, 3.9-221.0; P < .001). Conclusions and
      Relevance: Despite the improved specificity of the international recommendations
      over previous athlete-specific ECG criteria, abnormal ECG classification rates
      remain high in NBA athletes. The development of left ventricular concentric
      remodeling appears to have a significant influence on the prevalence of abnormal
      ECG classification and repolarization abnormalities in this athlete group.

PMID- 29214320
TI  - Suicide among agricultural, forestry, and fishery workers.
AB  - In their meta-analysis, Klingelschmidt and her associates (1) found that
      agricultural, forestry, and fishery workers are at 48% higher risk of suicide
      than the working-age population. Moreover, they found that the excess risk is
      even greater among Japanese agricultural workers than workers from other high
      income countries. There are several concerns regarding this meta-analysis. It
      appears that the excess risk has been overestimated for these workers.
      Furthermore, the excess risk in Japan is not different than other high-income
      countries. First, in a systematic review, a literature search is comprehensive. A
      search of a single database is unlikely to identify most of relevant studies, and
      these types of reviews are not therefore considered as systematic reviews (2). In
      this review, a specialized database (-PsycINFO) or a European database (EMBASE or
      -Scopus) was not searched. Second, following the PRISMA guidelines, the critical
      appraisal of included studies (quality assessment) is a requirement for a
      systematic review. In a meta-analysis of observational studies, selection bias
      and confounding should be ruled out. Third, the reviewers did not correctly
      extract confidence intervals (CI) for the estimates of several studies such as
      Hassler 2004, Fleming 1999, and Fragar 2011. Moreover, some studies reported both
      the least- and maximally adjusted risk estimates. The reviewers, however,
      extracted age- or the least-adjusted risk estimate. A confounder-adjusted
      estimate is a more appropriate estimate of the true association. In some studies
      [eg, Kposowa (3) Agerbo (4)], the excess risk dropped by 52-71% after adjustment
      for confounders. As a sensitivity analysis, the reviewers could limit their meta
      analysis to a subgroup of studies controlled for confounders. Fourth, the
      reviewers did not estimate an overall risk estimate for each study. They included
      the estimates of 2-6 subgroups for 22 studies in forest and funnel plots. A fixed
      effect meta-analysis is a more appropriate model to combine the subgroups of a
      single study. Moreover, for the assessment of publication bias, it is not
      appropriate to include several subsamples of a single study in a funnel plot.
      Using estimates of subgroups can change a large study into several smaller
      studies. Fifth, some of the included studies compared agricultural, forestry, and
      fishery workers with a specific occupational group. The reviewers could calculate
      a risk estimate using all other occupational groups as a comparison group and
      exclude those studies that did not provide sufficient data for estimating such a
      risk estimate. In some studies, the excess risk for agricultural, forestry, and
      fishery workers disappears after comparing with other occupational groups [eg,
      adjusted risk ratios (RR) for Kposowa (3) = 1.02, 95% CI 0.41-2.54]. This is a
      main reason for observed higher excess risk in Japanese workers. Wada et al (5)
      compared Japanese agricultural workers with sales workers and Suzuki et al (6)
      compared Japanese agricultural, forestry, and fishery workers with production
      process and related workers. Using all other occupational groups as a reference
      group, age-adjusted RR dropped from 3.53 (95% CI 2.84-4.38) to 2.61 (95% CI 2.10
      3.25) for Wada et al (5) and from 3.24 (CI 2.95-3.57, both sexes combined) to
      1.31 (CI 1.27-1.35 age-adjusted OR after excluding unemployed people) for Suzuki
      et al (6). The pooled estimate of these two register-based studies was 1.33 (95%
      CI 1.29-1.37) using a fixed model and 1.83 (95% CI 0.93-3.60) using a random
      model. Sixth, most of the included studies used register data, which had little
      information on the background characteristics of the participants. A majority of
      these studies controlled the estimates for age and sex only. Moreover, in this
      review, prospective cohort studies did not support the observed association. A
      meta-analysis of 11 case-control and prospective cohort studies shows no
      significant excess risk of suicide for agricultural, forestry, and fishery
      workers (pooled estimate = 1.02, 95% CI 0.71-1.47 for 6 cohort studies and 1.13,
      95% CI 0.92-1.39, I2 = 91% for 11 case control and cohort studies, combining
      maximally adjusted risk estimates and comparing agricultural, forestry, and
      fishery workers with all other occupational groups where possible). The excess
      risk found in this review (1) can thus largely be due to confounding. References
      1. Klingelschmidt J, Milner A, Khireddine-Medouni I, Witt K, Alexopoulos EC,
      Toivanen S, LaMontagne AD, Chastang JF, Niedhammer I. Suicide among agricultural,
      forestry, and fishery workers: a systematic literature review and meta-analysis.
      Scand J Work Environ Health. 2018;44(1):3-15. https://doi.org/10.5271/sjweh.3682.
      2. Puljak L. If there is only one author or only one database was searched, a
      study should not be called a systematic review. J Clin Epidemiol. 2017;91:4-5.
      https://doi.org/10.1016/j.jclinepi.2017.08.002.  3. Kposowa AJ. Suicide mortality
      in the United States: differentials by industrial and occupational groups. Am J
      Ind Med. 1999;36:645-52. https://doi.org/10.1002/(SICI)1097
      0274(199912)36:63.0.CO;2-T. 4. Agerbo E, Gunnell D, Bonde JP, Mortensen PB,
      Nordentoft M. Suicide and occupation: the impact of socio-economic, demographic
      and psychiatric differences. Psychol Med. 2007;37:1131-40.
      https://doi.org/10.1017/S0033291707000487.  5. Wada K, Gilmour S. Inequality in
      mortality by occupation related to economic crisis from 1980 to 2010 among
      working-age Japanese males. Sci Rep. 2016;6:22255.
      https://doi.org/10.1038/srep22255. 6. Suzuki E, Kashima S, Kawachi I, Subramanian
      SV. Social and geographical inequalities in suicide in Japan from 1975 through
      2005: a census-based longitudinal analysis. PLoS One. 2013;8:e63443.
      https://doi.org/10.1371/journal.pone.0063443.

PMID- 29214321
TI  - Hemithyroidectomy for low-risk follicular carcinoma of the thyroid: results from
      a regional hospital.
AB  - INTRODUCTION: Excellent outcomes after conservative thyroid surgery for low-risk
      follicular thyroid carcinoma (FTC) have been reported from highly specialised
      centres. However, it is uncertain whether low-volume hospitals can achieve
      similar treatment results. METHODS: At our institution, 49 patients with FTC were
      treated during the period 1991-2014. Patients with minimally invasive FTC (MIFTC)
      were usually treated with hemithyroidectomy. The demographic data, pathology,
      treatment modality and oncological outcomes of these patients were
      retrospectively evaluated. RESULTS: The tumours were classified as Stage I in
      40.8% of patients, Stage II in 32.7%, Stage III in 20.4% and Stage IV in 6.1%,
      according to the TNM classification system. Only 4 (8.2%) patients had widely
      invasive FTC (WIFTC). Vascular invasion or capsular invasion alone occurred in 9
      (19.1%) and 19 (40.4%) patients, respectively, while 19 (40.4%) patients had
      simultaneous vascular and capsular invasions. 34 (69.4%) patients with MIFTC
      initially underwent hemithyroidectomy, while 15 (30.6%) patients underwent total
      thyroidectomy. Ten patients who underwent total thyroidectomy received
      radioactive iodine ablation. The mean follow-up duration was 86.9 +/- 56.6
      months. There was no disease-specific mortality, although two patients with WIFTC
      remained alive with disease at the end of the study. The five-, ten- and 15-year
      overall survival rates were 95%, 91% and 84%, respectively. Five patients from
      the hemithyroidectomy group died due to other illnesses with no evidence of FTC.
      CONCLUSION: Satisfactory disease control and excellent survival for MIFTC is
      achievable by hemithyroidectomy in community hospitals. Total thyroidectomy
      should be reserved for WIFTC or aggressive tumours with nodal or distant
      metastasis.

PMID- 29214322
TI  - Road traffic accidents in children: the 'what', 'how' and 'why'.
AB  - INTRODUCTION: Road traffic accidents (RTAs) in Singapore involving children were
      evaluated, with particular focus on the epidemiology, surrounding circumstances
      and outcomes of these accidents. Key factors associated with worse prognosis were
      identified. We proposed some measures that may be implemented to reduce the
      frequency and severity of such accidents. METHODS: This was a retrospective study
      of RTAs involving children aged 0-16 years who presented to the Children's
      Emergency at KK Women's and Children's Hospital, Singapore, from January 2011 to
      June 2014. Data was obtained from the National Trauma Registry and analysed in
      tiers based on the Injury Severity Score (ISS). RESULTS: A total of 1,243
      accidents were reviewed. RTA victims included motor vehicle passengers (60.4%),
      pedestrians (28.5%), cyclists (9.9%) and motorcycle pillion riders (1.2%). The
      disposition of emergency department (ED) patients was consistent with RTA
      severity. For serious RTAs, pedestrians accounted for 63.6% and 57.7% of Tier 1
      (ISS > 15) and Tier 2 (ISS 9-15) presentations, respectively. Overall use of
      restraints was worryingly low (36.7%). Not restraining increased the risk of
      serious RTAs by 8.4 times. Young age, high ISS and low Glasgow Coma Scale score
      predicted a longer duration of intensive care unit stay. CONCLUSION: The
      importance of restraints for motor vehicle passengers or helmets for motorcycle
      pillion riders and cyclists in reducing morbidity requires emphasis. Suggestions
      for future prevention and intervention include road safety education, regulation
      of protective restraints, use of speed enforcement devices and creation of
      transport policies that minimise kerbside parking.

PMID- 29214323
TI  - Economic value of using partially hydrolysed infant formula for risk reduction of
      atopic dermatitis in high-risk, not exclusively breastfed infants in Singapore.
AB  - INTRODUCTION: Previous trials have demonstrated reductions in atopic dermatitis
      (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were
      fed until four months of age with 100% whey-based partially hydrolysed formula
      (PHF-W) versus standard cow's milk formula (CMF). We assessed the cost
      effectiveness of this intervention in Singapore. METHODS: Modelling techniques
      were used to simulate, from birth to Month 30, the incidence and
      clinical/economic burden of AD in high-risk, non-exclusively breastfed infants
      fed with PHF-W or CMF for up to four months. Epidemiologic and clinical data were
      from a local comparative trial. Expert opinion informed AD treatment patterns and
      outcomes. Outcomes included reduction in AD risk, time spent with AD, days
      without AD flare, quality-adjusted life years (QALYs) and direct/indirect costs.
      Multivariate probabilistic sensitivity analysis was used to assess model
      parameter uncertainty. RESULTS: Over 30 months, with the use of PHF-W instead of
      CMF, the proportion of children who developed AD and the time spent with AD
      decreased by 16.0% (28.3% vs. 44.3%) and 6.4 months, respectively, while time
      without AD flare and QALYs increased by 14.9 days and 0.021 QALYs per patient,
      respectively. Estimated AD-related discounted costs per child for PHF-W and CMF
      were SGD 771 and SGD 1,309, respectively (net savings: SGD 538). PHF-W was less
      expensive and more effective than CMF for 73%, and cost less than SGD 50,000 per
      QALY for 87% of all multivariate simulations. CONCLUSION: Early short-term
      nutritional intervention with PHF-W instead of CMF may reduce AD incidence and
      costs for healthy, high-risk, non-exclusively breastfed infants in Singapore.

PMID- 29214324
TI  - [Benefits of medical emergency teams : Mortality on normal wards and readmission
      to intensive care wards].
AB  - Medical emergency teams (MET) were implemented in many hospitals worldwide in
      order to identify patients at risk on normal wards and to initiate diagnostics
      and therapy without delay. Ideally, the implementation leads to prevention of
      cardiac arrests and unexpected deaths on normal wards, reduced rates of
      admissions to intensive care units and hospital mortality. Various track and
      trigger systems are available to identify such patients and for them to be
      assessed and treated within 30-45 min by the MET. The ideal personnel composition
      of METs has not yet been established. Whether the implementation of an MET
      generally leads to an improvement of treatment on normal wards or to a reduction
      in mortality in hospitals has not been finally clarified. Mortality and morbitidy
      (M&M) conferences can help to analyze if an individual clinic is likely to profit
      from the introduction of a MET.

PMID- 29214325
TI  - Anterior colporrhaphy: a standard operation? Systematic review of the technical
      aspects of a common procedure in randomized controlled trials.
AB  - INTRODUCTION: Anterior colporrhaphy (AC) is considered a standard procedure and
      is performed all over the world. However, not a single step of the procedure has
      ever been truly standardized and the rates of failure show a wide range in the
      literature from 0% up to 92%. The aim of this systematic review was to evaluate
      the differences in technique and procedure worldwide. METHODS: We performed a
      systematic literature search up to March 2016 using the MeSH terms "(anterior AND
      (colporrhaph* or colporhaph* or repair* or cystocel*)" using Preferred Reporting
      Items for Sytematic Reviews and Meta-Analyses (PRISMA). Only randomized
      controlled trials (RCT) were included in the systematic review. A 14-point
      checklist was used to assess the quality of surgery undertaken in each RCT.
      RESULTS: Forty RCTs from all over the world were included in the review. The
      indication for AC was urinary incontinence and/or pelvic organ prolapse. A
      detailed description of colporrhaphy was not provided even in the well-conducted
      RCTs. The review showed differences in each step of the procedure, in
      perioperative care, in anesthesia and in surgeon' experience. CONCLUSION: Our
      results highlight the problems concerning AC with the great range in
      postoperative outcomes. There is diversity in the anatomical structures used in
      the repair, in perioperative care and in the procedure itself.

PMID- 29214327
TI  - [Current techniques for shaping the nasal dorsum].

PMID- 29214326
TI  - Increased Solubility and Bioavailability of Hydroxy-Cr(III) Precipitates in the
      Presence of Hydroxamate Siderophores.
AB  - Siderophores are a diverse group of low molecular weight biogenic metallophores
      with a particular affinity for Fe(III) but they also have potential to complex a
      number of other polyvalent metal cations, including Cr(III). Here we show that
      two hydroxamate siderophores, desferrioxamine B and rhodotorulic acid, at
      environmentally relevant concentrations, facilitate the dissolution of hydroxy
      Cr(III) precipitates from a common layer silicate. Desferrioxamine B and
      rhodotorulic acid induced maximum initial Cr dissolution rates of 11.3 +/- 1.7 *
      10- 4  and 9.03 +/- 0.68 * 10- 4 umol m- 2 h- 1, respectively, yielding maximum
      solution Cr concentrations of 0.26 +/- 0.01 and 0.20 +/- 0.02 umol m- 2,
      respectively. These data demonstrate that hydroxamate siderophores may play an
      important role increasing the dispersal of Cr in natural environments, thus
      facilitating greater bioavailability of this potential toxin.

PMID- 29214328
TI  - 5-Azacytidine treatment and TaPBF-D over-expression increases glutenin
      accumulation within the wheat grain by hypomethylating the Glu-1 promoters.
AB  - KEY MESSAGE: 5-azaC treatment and TaPBF - D over-expression decrease C
      methylation status of three Glu - 1 gene promoters, and aid in enhancing the
      expression of the Glu - 1 genes. The wheat glutenins exert a strong influence
      over dough elasticity, but the regulation of their encoding genes has not been
      firmly established. Following treatment with 5-azacytidine (5-azaC), both the
      weight and glutenin content of the developing and mature grains were
      significantly increased. The abundance of transcript produced by the Glu-1 genes
      (encoding high-molecular-weight glutenin subunits), as well as those encoding
      demethylases and transcriptional factors associated with prolamin synthesis was
      higher than in grain of non-treated plants. These grains also contained an
      enhanced content of the prolamin box binding factor (PBF) protein. Bisulfite
      sequencing indicated that the Glu-1 promoters were less strongly C-methylated in
      the developing grain than in the flag leaf, while in the developing grain of 5
      azaC treated plants, the C-methylation level was lower than in equivalent grains
      of non-treated plants. Both Glu-1 transcript abundance and glutenin content were
      higher in the grain set by three independent over-expressors of the D genome
      homoeolog of TaPBF than in the grain set by wild type plants. When assessed 10
      days after flowering, the Glu-1 promoters' methylation level was lower in the
      developing grains set by the TaPBF-D over-expressor than in the wild type
      control. An electrophoretic mobility shift assay showed that PBF-D was able to
      bind in vitro to the P-box of Glu-1By8 and -1Dx2, while a ChIP-qPCR analysis
      revealed that a lower level of C-methylation in the Glu-1By8 and -1Dx2 promoters
      improved the TaPBF binding. We suggest that promoter DNA C-methylation is a key
      determinant of Glu-1 transcription.

PMID- 29214329
TI  - Time to surgery after hip fracture across Canada by timing of admission.
AB  - : The extent of Canadian provincial variation in hip fracture surgical timing is
      unclear. Provinces performed a similar proportion of surgeries within three
      inpatient days after adjustment. Time to surgery varied by timing of admission
      across provinces. This may reflect different approaches to providing access to
      hip fracture surgery. INTRODUCTION: The aim of this study was to compare whether
      time to surgery after hip fracture varies across Canadian provinces for
      surgically fit patients and their subgroups defined by timing of admission.
      METHODS: We retrieved hospitalization records for 140,235 patients 65 years and
      older, treated surgically for hip fracture between 2004 and 2012 in Canada
      (excluding Quebec). We studied the proportion of surgeries on admission day and
      within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries
      across provinces and by subgroups defined by timing of admission. Differences
      were adjusted for patient, injury, and care characteristics. RESULTS: Overall,
      provinces performed similar proportions of surgeries within the recommended three
      inpatient days, with all provinces requiring one additional day to perform the
      recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries
      on admission day than Ontario irrespective of timing of admission (difference =
      7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3%
      lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in
      Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario.
      These differences persisted for late weekday and weekend admissions. The time
      required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4
      days, respectively, across provinces by timing of admission. CONCLUSIONS:
      Provinces performed similarly with respect to recommended time for hip fracture
      surgery. The proportion of surgeries on admission day, and time required to
      complete 33% and 66% of surgeries, varied across provinces and by timing of
      admission. This may reflect different provincial approaches to providing access
      to hip fracture surgery.

PMID- 29214331
TI  - [Imaging of muscular diseases].

PMID- 29214330
TI  - Oxidative Stress in Kidney Diseases: The Cause or the Consequence?
AB  - Exaggerated oxidative stress (OS) is usually considered as a disturbance in
      regular function of an organism. The excessive levels of OS mediators may lead to
      major damage within the organism's cells and tissues. Therefore, the OS
      associated biomarkers may be considered as new diagnostic tools of various
      diseases. In nephrology, researchers are looking for alternative methods
      replacing the renal biopsy in patients with suspicion of chronic kidney disease
      (CKD). Currently, CKD is a frequent health problem in world population, which can
      lead to progressive loss of kidney function and eventually to end-stage renal
      disease. The course of CKD depends on the primary disease. It is assumed that one
      of the factors influencing the course of CKD might be OS. In the current work, we
      review whether monitoring the OS-associated biomarkers in nephrology patients can
      support the decision-making process regarding diagnosis, prognostication and
      treatment initiation.

PMID- 29214334
TI  - Using Four-Layer Sculpted Rib Cartilage Framework to Increase Transverse Height
      of the Reconstructive Ear in One Operative Stage for Microtia Patients.
AB  - PURPOSE: This case study improves an operative method of ear reconstruction for
      microtia patients by using a four-layer rib cartilage framework to increase
      transverse height of the reconstructive ear to a natural level in one operative
      stage. MATERIALS AND METHODS: The procedures of ear reconstruction were conducted
      from February 2014 to May 2016. The ear framework used in the procedures was
      fabricated from autologous rib cartilage into a four-layer spliced sculpture.
      Totally 23 patients with unilateral microtia were willing to be enrolled in this
      study. RESULTS: After the operation, 23 patients achieved 2.3-2.8 cm transverse
      height of reconstructed ears, which was basically the same as the normal side.
      Both patients and their families felt satisfied with the results. Follow-up was
      performed at 6-16 months after the procedures. Only one case showed significantly
      lowered transverse height of the reconstructed ear, compared to the normal one.
      It was due to the sleeping position of the patient (10-year-old boy), which put
      the reconstructed ear under pressure and reduced the transverse height of the
      ear. CONCLUSIONS: The method of four-layer sculpted autologous rib cartilage ear
      reconstruction has good clinical effect. It can provide a reconstructed ear that
      reaches normal transverse height and avoids a third operation to increase the
      transverse height by rib cartilage transplantation. 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- 29214333
TI  - Primary cardiac tumors associated with genetic syndromes: a comprehensive review.
AB  - Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas
      in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be
      different in syndromic forms, and on imaging children sometimes demonstrate
      additional manifestations of the underlying syndrome. We discuss the imaging
      appearance of cardiac tumors occurring in the framework of a genetic syndrome,
      the findings that suggest an underlying syndrome, and the impact on management.

PMID- 29214335
TI  - Commentary: Mastopexy on Reconstructed Breast Following Massive Weight Loss: An
      Innovative Technique Using Dermo-Capsular Flaps.

PMID- 29214336
TI  - The Efficacy and Safety of Early Postoperative Botulinum Toxin A Injection for
      Facial Scars.
AB  - BACKGROUND: Scars widen when the underlying musculature pulls apart suture lines,
      and scars oriented against relaxed skin tension lines are especially susceptible
      to these distraction forces. Because botulinum toxin A (BTA) induces complete
      muscle paralysis, the purpose of the current study was to evaluate the effects of
      BTA using both observer-dependent qualitative assessments and quantitative
      measurements to verify its beneficial effects on facial scarring. METHODS:
      Patients with vertical forehead lacerations, treated by primary closure, were
      randomly assigned to two groups: one (n = 15) received BTA injections within 5
      days of primary closure and the other (n = 15) received no further treatment.
      Vancouver scar scale (VSS) scores and wound width were determined at the 1-month
      and 6-month follow-up visits. Quantitative color differences between the scar and
      surrounding normal skin, using the Commission International d'Eclairage L*a*b*
      color coordinates, were measured and compared by analyzing photographs. RESULT:
      Improved VSS scores, less increase in wound width, and less scar discoloration
      were noted among patients treated with BTA injections compared with the control
      group. These differences were observed at the 6-month visit, but not at the 1
      month visit. CONCLUSION: BTA injection improves scar quality when injected during
      the early postoperative days. LEVEL OF EVIDENCE I: 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- 29214338
TI  - ?

PMID- 29214337
TI  - Sleep-disordered breathing in patients with sickle cell disease.
AB  - Sickle cell disease is one of the most common hereditary hemoglobinopathies
      worldwide, and its vaso-occlusive and hemolytic crises cause considerable patient
      morbidity. A growing body of evidence has shown that sleep-disordered breathing,
      and in particular, obstructive sleep apnea, occurs at high frequency in the
      sickle cell population, and that there is significant overlap in the underlying
      pathophysiology of these two conditions. Through a variety of mechanisms
      including nocturnal hypoxemia and increased oxidative stress, production of pro
      inflammatory cytokines, and endothelial dysfunction, sickle cell anemia and sleep
      disordered breathing potentiate each other's clinical effects and end-organ
      complications. Here, we will review the shared pathophysiologic mechanisms of
      these conditions and discuss their clinical sequelae. We will also examine the
      results of studies that have been carried out with clinical intervention of
      nocturnal hypoxemia in patients with sickle cell disease in the attempts to
      overcome the complications of the disease. Finally, we will propose the areas of
      investigation that merit further investigations in future in patients with sickle
      cell disease and sleep-disordered breathing.

PMID- 29214339
TI  - Genes involved in Beauveria bassiana infection to Galleria mellonella.
AB  - The ascomycete fungus Beauveria bassiana is a natural pathogen of hundreds of
      insect species and is commercially produced as an environmentally friendly
      mycoinsecticide. Many genes involved in fungal insecticide infection have been
      identified but few have been further explored. In this study, we constructed
      three transcriptomes of B. bassiana at 24, 48 and 72 h post infection of insect
      pests (BbI) or control (BbC). There were 3148, 3613 and 4922 genes differentially
      expressed at 24, 48 and 72 h post BbI/BbC infection, respectively. A large number
      of genes and pathways involved in infection were identified. To further analyze
      those genes, expression patterns across different infection stages (0, 12, 24,
      36, 48, 60, 72 and 84 h) were studied using quantitative RT-PCR. This analysis
      showed that the infection-related genes could be divided into four patterns:
      highly expressed throughout the whole infection process (thioredoxin 1); highly
      expressed during early stages of infection but lowly expressed after the insect
      death (adhesin protein Mad1); lowly expressed during early infection but highly
      expressed after insect death (cation transporter, OpS13); or lowly expressed
      across the entire infection process (catalase protein). The data provide novel
      insights into the insect-pathogen interaction and help to uncover the molecular
      mechanisms involved in fungal infection of insect pests.

PMID- 29214340
TI  - Management and outcomes of treating pediatric medulloblastoma: an eight years'
      experience in an Iranian pediatric center.
AB  - PURPOSE: The clinical management of pediatric medulloblastoma requires a
      multidisciplinary approach, which can be challenging, especially in low- and
      middle-income countries. The aim of this study was to identify current challenges
      and describe the treatment and outcomes of Iranian pediatric patients with
      medulloblastoma who were referred to our center in Tehran, Iran. METHODS: Our
      retrospective review included 126 patient records from April 2007 to May 2015.
      The records were analyzed for epidemiologic features, treatment modalities,
      overall survival, and progression-free survival. Data were analyzed using SPSS
      22.0 software. RESULTS: Median age at diagnosis was 6 years (male:female ratio,
      2.3:1). At the time of diagnosis, 7 patients were 2 years or younger, and 76
      (60.3%) were categorized as having high-risk disease. Overall, 100 patients had
      gross or near-total surgical resection. Cerebral spinal fluid involvement was
      detected in 22.2% of the patients tested, and spinal involvement was detected in
      25% of the patients who underwent spinal MRI. Metastasis stages at the time of
      diagnosis were as follows: M0: 48.4% patients, M1: 16.7%, M2: 5.5%, and M3:
      21.4%. Median times of follow-up and progression-free survival were 16 and 12
      months, respectively. Probability of 7-year overall survival and progression-free
      survival were 59 and 53.8%, respectively. CONCLUSIONS: Results of the current
      retrospective study emphasize the need for implementing measures to improve
      outcome for our patients with medulloblastoma. Such measures include a
      multidisciplinary approach, unified national treatment guidelines, better disease
      and metastasis staging, twinning initiatives, and seeking a second opinion when
      needed.

PMID- 29214341
TI  - Sternocostal slipping rib syndrome.
AB  - PURPOSE: Classical slipping rib syndrome (SRS) can be subclassified based on
      anatomical location. We describe our experience with three patients suffering
      from symptomatic sternocostal slipping rib syndrome (SCSRS), a much less common
      variant of SRS. METHODS: This was a retrospective review of patients with SRS
      from 1988 to 2016. Described is our experience. RESULTS: Of 44 patients
      identified with SRS, three patients underwent operations for SCSRS variant. All
      three had significant pain and point tenderness at the sternocostal junction, and
      all experienced a popping sensation localized to this area. The mean age at onset
      was 14.3 years and mean time to diagnosis was 1.3 years. All patients experienced
      total resolution of symptoms following localized excision of the offending
      cartilage. CONCLUSIONS: A high index of suspicion based on history and physical
      examination are key to the early diagnosis of SCSRS. Excision of the symptomatic
      cartilage is effective for treatment.

PMID- 29214342
TI  - Editorial.

PMID- 29214343
TI  - Correction to: Surgical and oncological outcomes after complete mesocolic
      excision in right-sided colon cancer compared with conventional surgery: a
      retrospective, single-institution study.
AB  - The publisher regrets that some errors were introduced during the production
      process. The errors are now presented correctly in this article.

PMID- 29214344
TI  - [OCT-Angiography in diabetic maculopathy : Comparison between microaneurysms and
      the foveal avascular zone with flourescein angiography].
AB  - BACKGROUND: Optical coherence tomography angiography allows an exact
      visualization of retinal vascular changes. To interpret the possibilities and
      limitations using OCTA in clinical practice, we analysed the quality of OCTA
      findings concerning the evaluability. Furthermore, we correlated our OCTA
      findings with fluorescein angiography (FAG) in relation of the presence of
      microaneurysms (MA) and enlargement of the foveal avascular zone (FAZ) in
      diabetic maculopathy. PATIENTS AND METHODS: 30 eyes from 15 patients with
      diabetic maculopathy were imaged in 3 * 3mm volume scans and were depicted in
      OCTA mode (SSADA algorithm). By using the automatic segmentation we analysed the
      vascular changes in the superficial and deep capillary plexus and classified them
      concerning their qualitative evaluability. We analysed the number of MA in OCTA
      and fluorescein angiography and correlated them using an overlay technique. We
      analysed the presence of MA in the superficial and deep capillary plexus in OCTA
      as well. Furthermore we measured the enlargement of the foveal zone with both
      methods. RESULTS: In a large number of eyes we could not identifiy MA or measure
      the enlargement of the FAZ because of poor OCTA or FA quality. In the
      morphological analysis of our findings we identified a comparable number of MA in
      both methods, although the localization of the MA was different in both methods
      in a large number of eyes. The majority of MA was located in the deep capillary
      plexus. The extension of the foveal avascular zone measured in FA revealed a good
      correlation to the automatically measured "nonflow area" in the OCTA. CONCLUSION:
      OCTA allows a good visualization of characteristic vascular changes in diabetic
      maculopathy. In spite of technical limitations OCTA generates a three-dimensional
      visualisation of avascular changes. The majority of microaneurysms detected by
      OCTA showed a corresponding finding in FA. The central avascular zone (FAZ) in
      OCTA correlates well with the findings from FA. OCTA represents an important
      additional diagnostic tool to interpret vascular changes in DM.

PMID- 29214345
TI  - An investigation of the independent risk factors that differentiate gout from
      pseudogout in patients with crystal-induced acute arthritis: a cross-sectional
      study.
AB  - OBJECTIVES: To identify independent risk factors that differentiate gout from
      pseudogout in patients that present with crystal-induced acute arthritis.
      METHODS: This cross-sectional study was conducted at Siriraj Hospital (Bangkok,
      Thailand) during the 25 May 2014-28 November 2014 study period. Patients who
      presented with crystal-induced acute arthritis were eligible for inclusion.
      Diagnosis of gout or pseudogout was made by microscopic visualization and
      analysis of crystals in synovial fluid. Patients with other causes of acute
      arthritis were excluded. Patients diagnosed with gout were compared with patients
      diagnosed with pseudogout and factors with a p value less than 0.05 were included
      in logistic regression analysis. RESULTS: A total of 103 patients were included.
      Gout and pseudogout were established in 59 (56.7%) and 44 (42.3%) patients,
      respectively. Gout patients were younger than pseudogout patients (66.9 +/- 14.5
      vs. 78.9 +/- 12.0 years; p = 0.0001); had higher BMI (22.9 +/- 2.5 vs. 21.0 +/-
      2.5 kg/m2; p = 0.001); had history of recurrent arthritis (91.5 vs. 9.1%; p =
      0.001); had higher prevalence of below-knee arthritis (66.1 vs. 31.8%; p =
      0.001); had less periarticular soft tissue swelling (57.6 vs. 81.8%; p = 0.01);
      and had hyperuricemia (8.0 +/- 2.5 vs. 5.6 +/- 2.7; p = 0.001). In adjusted
      multivariate analysis, hyperuricemia during acute arthritis/gouty attack
      characterized gout (OR 2.08, 95% CI 1.2-3.6), while monoarticular attack (OR
      4.12, 95% CI 1.3-13.0) and periarticular soft tissue swelling (OR 4.03, 95% CI
      1.1-14.9) were indications for pseudogout. CONCLUSIONS: The independent risk
      factors were found to differentiate gout from pseudogout: Gout: hyperuricemia
      during gouty attack; Pseudogout: monoarticular attack and periarticular soft
      tissue swelling.

PMID- 29214346
TI  - Comparative genomics reveals the presence of putative toxin-antitoxin system in
      Wolbachia genomes.
AB  - Multiple toxin-antitoxin (TA) systems are housed in different locations within
      the bacterial genome and are known to be associated with various cellular
      processes and stress-related adaptation. In endosymbionts, although, the TA
      system has scarce occurrence but studies have highlighted its presence in
      enhancing host-symbiont interactions. Wolbachia, an obligate endosymbiont, has
      recently been proposed as a biocontrol agent which may be helpful in controlling
      vector-borne diseases. There are reports suggesting the role of TA system in
      inducing cytoplasmic incompatibility in case of Wolbachia, however, the
      underlying mechanism is still not known. The present study, therefore, aims at
      exploring the diversity of TA system in four novel (sourced from India) and three
      reference genomes (NCBI) of Wolbachia strains. Interestingly, we found several
      putative toxins and antitoxins of RelEB family of Type II TA system in these
      Wolbachia genomes. The results show wMel genome possessed more number of putative
      TA loci than wRi genome. In addition, searching through the other sequenced
      Wolbachia genomes in NCBI, a complete absence of TA system was observed in
      Wolbachia-infected nematodes. The sequence-wide analysis of all the putative
      RelEB proteins present amongst the Wolbachia endosymbiont and within the free
      living bacterial genomes reveal strain-specific similarities and conserved
      sequences. However, large amount of sequence diversity was observed between
      Wolbachia and free-living bacteria. Understanding this sequence variation may
      help shed light on the differences between these two forms of bacteria and could
      also explain their niche preferences.

PMID- 29214347
TI  - Partial phenotype conversion and differential trait response to conditions of
      husbandry in mice.
AB  - Functional genome analysis usually is performed on the level of genotype
      phenotype interaction. However, phenotypes also depend on the relations between
      genomes and environment. In our experimental system, we observed differential
      response to environmental factors defined by different conditions of husbandry in
      a semi-barrier unit or in a SPF (specific pathogen free) barrier unit, which
      resulted in partial reversal of phenotypes previously observed under semi-barrier
      conditions. To provide an update of basic phenotypes in unselected and randomly
      mated controls (DUC) and long-term selected DUhTP (Dummerstorf high treadmill
      performance) mice in the SPF facility, we compared growth parameters,
      reproductive performance, the accretion of muscle and fat mass, physical
      activity, and running performance as well as food intake in all experimental
      groups. For selected parameters, the comparative analysis spans more than 30
      generations. In DUC mice, under SPF conditions a more than threefold (P < 0.0001)
      higher subcutaneous fat mass, higher muscle mass by about 25% (P < 0.0001), but
      lower epididymal fat mass in DUhTP mice by about 20% (P < 0.0001) were observed.
      In SPF husbandry, body weight increased to a stronger extent in adult DUC mice (~
      20%; P < 0.0001) than in DUhTP mice (~ 8%; P = 0.001). The concentrations of IGF
      1 and IGFBPs in the serum as well as the liver weights were similar in all
      experimental groups, indicating growth effects independent of the somatotropic
      axis. Under SPF conditions the litter size at birth increased in DUC mice (P <
      0.001) but not in DUhTP mice. The differential effect of husbandry on body
      weights at day 21 and concentrations of triglycerides in the serum of our model
      were due to the different diets used in the semi-barrier and in the SPF facility.
      Our results demonstrate differential trait response to environmental factors
      resulting in partial phenotype conversion in our experimental system. The
      existence of conditional phenotypes as a result of genotype-environment
      interactions points to the importance of environmental factors in functional
      genome analysis.

PMID- 29214348
TI  - Effect of laser-assisted zona thinning, during assisted reproduction, on
      pregnancy outcome in women with endometriosis: randomized controlled trial.
AB  - OBJECTIVE: To compare the ICSI-ET outcomes in patients with endometriosis with or
      without laser-assisted zona pellucida thinning. DESIGN: Randomized controlled
      trial. SETTING: The study was conducted in the Obstetrics & Gynecology
      Department, Cairo University hospital, and two private IVF centers in Cairo &
      Beni-Suif from July 2015 to January 2017 upon infertile and known endometriosis
      patients who planned to do ICSI-ET. INTERVENTIONS: Before randomization, all
      patients received the same ovarian stimulation preparation, oocyte retrieval
      procedures, and the same intracytoplasmic sperm injection procedures. After
      randomization, laser-assisted hatching was performed only for embryos of 158
      patients, while the other group (n = 150) no laser-assisted hatching was made.
      The verification of pregnancy was achieved by the serum hCG concentration 14 days
      after the embryo transfer, and the clinical pregnancy was confirmed 2 weeks later
      by the presence of gestational sac with pulsating fetal pole on vaginal
      ultrasonography. MEASUREMENTS: The main outcome measures were the clinical
      pregnancy rate and the clinical implantation rate. MAIN RESULTS: Both groups were
      comparable with regard their baseline characteristics, baseline hormonal profile,
      the ovarian stimulation characteristics, and the ovulation characteristics. The
      mean number of embryos developed per patient and the mean transferred number of
      embryos per patient were comparable between groups (p value > 0.05). The
      implantation rate was significantly higher (p value 0.002) in the study group
      than the control group with an odds ratio of 1.86 (CI 95% 1.24-2.80) and NNT
      13.81 (CI 95% 8.35-39.94). The clinical pregnancy rate, was significantly (p
      value 0.022) higher in the study group than in the control group with an odds
      ratio of 1.79 (CI 95% 1.05-3.06) and NNT 9.57 (CI 95% 5.03-98.99). CONCLUSION:
      That laser-assisted hatching by thinning of the zona pellucida may be a suitable
      method to improve the ICSI-ET outcomes, in term of the implantation and the
      pregnancy rates, in cases of endometriosis. CLINICAL TRIAL REGISTRATION: Pan
      African Clinical Trials Registry (PACTR),
      http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR20150200
      022393 , PACTR201602001467322.

PMID- 29214349
TI  - Ion channels as part of macromolecular multiprotein complexes : Clinical
      significance.
AB  - Ion channels and Ca2+-handling proteins involved in the regulation of cardiac
      electrophysiology and contractility are organized in macromolecular multiprotein
      complexes. Recent molecular and cellular studies have significantly enhanced our
      understanding of the composition of these macromolecular complexes and have
      helped to elucidate their role in the dynamic regulation of ion channel function.
      Moreover, it has become clear that alterations in the composition of ion channel
      macromolecular complexes, for example, due to genetic mutations or acquired
      alterations in the expression of individual components, may lead to ion channel
      dysfunction and arrhythmogenesis. Here, we review novel insights into the
      composition of the major ion channel macromolecular complexes and discuss the
      potential clinical significance of alterations in these dynamic multiprotein
      structures.

PMID- 29214350
TI  - Co-culture of human fibroblasts and Borrelia burgdorferi enhances collagen and
      growth factor mRNA.
AB  - Skin fibrosis has been reported in Borrelia burgdorferi infection in Europe, but
      has been questioned by several authors. The objective of the present study was to
      examine the interaction of skin fibroblasts with B. burgdorferi sensu stricto B31
      (BB) and B. afzelii (BA) in vitro by electron microscopy. We also determined the
      expression of collagen type I, TGF-beta, FGF-1, calreticulin (CALR), decorin
      (DCN), and PDGF-alpha at the mRNA level in Borrelia/fibroblast co-cultures.
      Intact Borrelia attach to and transmigrate fibroblasts, and undergo cystic
      transformation outside the fibroblasts. Fibroblasts preserve their vitality and
      express a prominent granular endoplasmic reticulum, suggesting activated protein
      synthesis. On two different semi-quantitative real-time PCR assays, BB- and
      BA/fibroblast co-cultures showed a significant induction of type I collagen mRNA
      after 2 days compared to fibroblasts (fourfold for BA and 1.8-fold for BB; p <
      0.02). In addition, there was a significant upregulation of mRNA expression of
      TGF-beta, CALR, PDGF-alpha, and DCN in BA and BB co-cultures compared to control
      fibroblasts in monolayer cultures after 2 days (p < 0.01). The BA/fibroblast co
      culture induced a considerably greater upregulation of collagen and growth factor
      mRNA compared to BB/fibroblast co-culture. In contrast, a significant down
      regulation of FGF-1 (20-fold for BA and 4.5-fold for BB) mRNA expression was
      detected in co-cultures compared to controls (p < 0.01). The results of the study
      support the hypothesis that BB sensu lato, and BA in particular, enhances
      collagen mRNA expression and can stimulate growth factors responsible for
      increased collagen production.

PMID- 29214352
TI  - Ablation of very late recurrence after initially successful ablation of atrial
      fibrillation.

PMID- 29214351
TI  - Regenerative medicine for the esophagus.
AB  - Advances in tissue engineering techniques have made it possible to use human
      cells as biological material. This has enabled pharmacological studies to be
      conducted to investigate drug effects and toxicity, to clarify the mechanisms
      underlying diseases, and to elucidate how they compensate for impaired organ
      function. Many researchers have tried to construct artificial organs using these
      techniques, but none has succeeded in growing a whole organ. Unlike other
      digestive organs with complicated functions, such as the processing and
      absorption of nutrients, the esophagus has the relatively simple function of
      transporting content, which can be replicated easily by a substitute. In
      regenerative medicine, various combinations of materials have been applied,
      including scaffolding, cell sources, and bioreactors. Exciting results of tissue
      engineering techniques for the esophagus have been reported. In animal models,
      replacing full-thickness and full-circumferential defects remains challenging
      because of stenosis and leakage after implantation. Although many reports have
      manipulated various scaffolds, most have emphasized the importance of both
      epithelial and mesenchymal cells for the prevention of stenosis. However, the
      results of repair of partial full-thickness defects and mucosal defects have been
      promising. Two successful approaches for the replacement of mucosal defects in a
      clinical setting have been reported, although in contrast to the many animal
      models, there are few pilot studies in humans. We review the recent results and
      evaluate the future of regenerative medicine for the esophagus.

PMID- 29214353
TI  - Complete bladder neck preservation promotes long-term post-prostatectomy
      continence without compromising midterm oncological outcome: analysis of a
      randomised controlled cohort.
AB  - PURPOSE: The only RCT available on complete bladder neck preservation (cBNP)
      during radical prostatectomy reported superior continence and QoL outcomes in the
      first 12 months after cBNP. We provide the first data on long-term urinary
      continence, QoL and biochemical recurrence (BCR) after complete bladder neck
      preservation in a randomised controlled cohort. METHODS: After approval by IRB,
      199 men recruited for the randomised, controlled single-blind Heidelberger cBNP
      Study had prostatectomy performed with (cBNP) or without (noBNP) complete bladder
      neck preservation. Only men with renewed consent for this follow-up were
      evaluated for continence, QoL outcomes and BCR by ICIQ-SF self-assessment
      questionnaire, Pad-use/day and PSA levels. Students-t test, Pearson's Chi-square,
      Fishers exact test and multiple logistic regression analyses were applied.
      RESULTS: Mean follow-up was approx. 4 years. There were no significant
      differences in baseline characteristics between responders/non-responders or
      between study groups. We noted significantly higher continence rates (p = 0.004),
      less pad-use (p < 0.001), reduced frequency (p = 0.023) and amount (p = 0.009) of
      urine loss, and higher QoL outcomes (p = 0.012) after cBNP. A younger age
      positively influenced continence (OR = 0.91), but the multivariate analysis found
      cBNP to be the only independent predictor of continence (p = 0.008; OR = 8.1). pT
      stage was the only predictor for positive surgical margins (PSM; p < 0.001).
      There was no significant difference in pT stage (p = 0.23) or BCR (p = 0.63)
      between study groups and also no significant correlation between BCR and presence
      (p = 0.26) or localisation (p = 0.11) of PSM, nerve sparing (p = 0.70), surgeon
      (p = 0.41), preoperative PSA (p = 0.53) or pT stage (p = 0.17). No cancer-related
      death was noted. CONCLUSIONS: Results of this first follow-up on a prospective
      randomised controlled cohort demonstrate that cBNP is associated with
      significantly higher continence and QoL outcomes without compromising cancer
      control making cBNP a novel objective during radical prostatectomy.

PMID- 29214354
TI  - Wide-field autofluorescence-guided TUR-B for the detection of bladder cancer: a
      pilot study.
AB  - PURPOSE: The aim of this pilot study was to assess the feasibility and value of
      wide-field autofluorescence imaging (AFI) for the detection of bladder cancer
      during transurethral resection of the bladder (TUR-B). METHODS: For imaging, the
      D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band
      pass filter (~ 480-780 nm) at the eyepiece of the endoscope were used. The
      excitation light wavelength was 440 nm. Representative spectral measurements of
      tissue autofluorescence (AF) were performed using a spectrometer attached behind
      the AF band pass filter in selected patients. During TUR-B, cystoscopy was
      performed in white light (WL) followed by wide-field AFI. Lesions were classified
      as suspicious or normal using either modality. RESULTS: Representative spectral
      measurements using excitation at a wavelength of 440 nm resulted in significantly
      lower fluorescence intensity of malignant versus non-malignant tissue. Overall,
      56 lesions (30 cancerous and 26 non-malignant) in 25 patients were assessed and
      classified by wide-field AFI. Papillary tumors as well as flat lesions lacked the
      green fluorescence seen in normal urothelium, thus emerging as "brown-reddish"
      areas. When compared with histopathological findings, the pooled per-lesion
      sensitivity and specificity for AF were 96.7 and 53.8%, respectively. For WL
      these values were 86.7 and 69.2%, respectively. CONCLUSION: Wide-field AFI
      imaging during TUR-B is simple and easy to use. Our preliminary data suggest that
      AFI has the potential to increase the detection rates of bladder tumors compared
      with WL without the need of intravesical instillation prior to the procedure.

PMID- 29214356
TI  - More predictive markers were identified for trastuzumab-induced cardiotoxicity.

PMID- 29214355
TI  - Biological production of L-malate: recent advances and future prospects.
AB  - As intermediates in the TCA cycle, L-malate and its derivatives have been widely
      applied in the food, pharmaceutical, agriculture, and bio-based material
      industries. In recent years, biological routes have been regarded as very
      promising approaches as cost-effective ways to L-malate production from low
      priced raw materials. In this mini-review, we provide a comprehensive overview of
      current developments of L-malate production using both biocatalysis and microbial
      fermentation. Biocatalysis is enzymatic transformation of fumarate to L-malate,
      here, the source of enzymes, catalytic conditions, and enzymatic molecular
      modification may be concluded. For microbial fermentation, the types of
      microorganisms, genetic characteristics, biosynthetic pathways, metabolic
      engineering strategies, fermentation substrates, and optimization of cultivation
      conditions have been discussed and compared. Furthermore, the combination of
      enzyme and metabolic engineering has also been summarized. In future, we also
      expect that novel biological approaches using industrially relevant strains and
      renewable raw materials can overcome the technical challenges involved in cost
      efficient L-malate production.

PMID- 29214357
TI  - Investigation and analysis of osteoporosis, falls, and fragility fractures in
      elderly people in the Beijing area: a study on the bone health status of elderly
      people >= 80 years old with life self-care.
AB  - : Among >= 80 years old and under life self-care in the Beijing area, the
      prevalences of osteoporosis, falls, and fragility fracture were high; and these
      prevalences were even higher in women. The treatment rate of osteoporosis is very
      low. Therefore, comprehensive and standardized prevention and treatment should be
      promoted. PURPOSE: The purpose of this study is to investigate prevalence of
      osteoporosis, falls, and fragility fractures in this population, and analyze
      related factors, in order to provide a basis for standardized prevention and
      treatment. METHODS: From August 2015 to August 2016 in Beijing City, a total of
      175 elderly individuals, who were >= 80 years old and had good self-care ability,
      were included into this study. The questionnaire, risk of falls, grip force, and
      walking speed were measured, and the Timed Up and Go test (TUG) and chair-rising
      test (CRT) were performed. RESULTS: Compared to women, men have higher rates of
      smoking, drinking, drinking strong tea, longer outdoor activity time, as well as
      larger muscle strength and pace, and lower consumption of dairy products, fall
      risk assessment scale (FRA) score, 25OHD, administration rates of calcium and
      anti-osteoporosis drugs (P < 0.05, P < 0.01). Compared with men, women had higher
      bone turnover markers (P1NP, beta-CTx, and OC) (P < 0.05, P < 0.01) and lower
      levels of sex hormones (E2, T) (P < 0.01). The overall prevalence of osteoporosis
      was 24.6%, and this was significantly higher in women than in men (52.5 vs. 9.6%,
      P < 0.01). Among these subjects, 62.9% had a history of fall after 80 years old,
      and this rate was higher in women than in men (77 vs. 55.3%, P < 0.01). The
      overall prevalence of fragility fractures was 25.1%, which was higher in women
      than in men (45.9 vs. 14.0%, P < 0.01). Risk factors included falls after age 80,
      high FRA score, and reduction in bone density of lumbar vertebrae 1-4, and odds
      ratio (OR) was 12.195, 1.339, and 0.076, respectively (P < 0.01). Anti
      osteoporosis therapy was only performed on a small number of patients with
      fractures. CONCLUSION: The prevalences of falls, prior fracture, and low BMD were
      high among >= 80 years old and under life self-care in the Beijing area.
      Therefore, a comprehensive approach to assessment and treatment should be
      promoted.

PMID- 29214358
TI  - Multiple timescale analysis of the urban heat island effect based on the
      Community Land Model: a case study of the city of Xi'an, China.
AB  - Urban heat islands (UHIs) are the phenomenon of urban regions usually being
      warmer than rural regions, which significantly impacts both the regional
      ecosystem and societal activities. Numerical simulation can provide spatially and
      temporally continuous datasets for UHI analysis. In this study, a spatially and
      temporally continuous ground temperature dataset of Xi'an, China was obtained
      through numerical simulation based on the Community Land Model version 4.5
      (CLM4.5), at a temporal resolution of 30 min and a spatial resolution of 0.05?*
      0.05?. Based on the ground temperature, the seasonal average UHI intensity (UHII)
      was calculated and the seasonal variation of the UHI effect was analyzed. The
      monthly variation tendency of the urban heat stress was also investigated. Based
      on the diurnal cycle of ground temperature and the UHI effect in each season, the
      variation tendencies of the maximum, minimum, and average UHII were analyzed. The
      results show that the urban heat stress in summer is the strongest among all four
      seasons. The heat stress in urban areas is very significant in July, and the UHII
      is the weakest in January. Regarding the diurnal cycle of UHII, the maximum
      always appears at 06:30 UTC to 07:30 UTC, while the minimum intensity of the UHI
      effect occurs at different times in the different seasons. The results of this
      study could provide a reference for policymakers about how to reduce the damage
      caused by heat stress.

PMID- 29214359
TI  - Theoretical studies of the decomposition mechanisms of 1,2,4-butanetriol
      trinitrate.
AB  - Density functional theory (DFT) and canonical variational transition-state theory
      combined with a small-curvature tunneling correction (CVT/SCT) were used to
      explore the decomposition mechanisms of 1,2,4-butanetriol trinitrate (BTTN) in
      detail. The results showed that the gamma-H abstraction reaction is the initial
      pathway for autocatalytic BTTN decomposition. The three possible hydrogen atom
      abstraction reactions are all exothermic. The rate constants for autocatalytic
      BTTN decomposition are 3 to 1040 times greater than the rate constants for the
      two unimolecular decomposition reactions (O-NO2 cleavage and HONO elimination).
      The process of BTTN decomposition can be divided into two stages according to
      whether the NO2 concentration is above a threshold value. HONO elimination is the
      main reaction channel during the first stage because autocatalytic decomposition
      requires NO2 and the concentration of NO2 is initially low. As the reaction
      proceeds, the concentration of NO2 gradually increases; when it exceeds the
      threshold value, the second stage begins, with autocatalytic decomposition
      becoming the main reaction channel.

PMID- 29214361
TI  - ForceGen: atomic covalent bond value derivation for Gromacs.
AB  - A large number of crystallographic protein structures include ligands, small
      molecules and post-translational modifications. Atomic bond force values for
      computational atomistic models of post-translational or non-standard amino acids,
      metal binding active sites, small molecules and drug molecules are not readily
      available in most simulation software packages. We present ForceGen, a Java tool
      that extracts the bond stretch and bond angle force values and equilibrium values
      from the Hessian of a Gaussian vibrational frequency analysis. The parameters are
      compatible with force fields derived using the second order tensor of the
      Hessian. The output is formatted with the Gromacs topology in mind. This study
      further demonstrates the use of ForceGen over the quantum mechanically derived
      structures of a small organic solvent, a naturally occurring protein crosslink
      derived from two amino acids following post-translational modification and the
      amino acid ligands of a zinc ion. We then derive Laplacian bond orders to
      understand how the resulting force values relate back to the quantum mechanical
      model. The parameterisation of the organic solvent, toluene, was verified using
      Molecular Mechanics simulations. The structural data from the simulation compared
      well with the quantum mechanical structure and the system density compared well
      with experimental values.

PMID- 29214363
TI  - Correction to: Ibrutinib does not prolong the corrected QT interval in healthy
      subjects: results from a thorough QT study.
AB  - The author would like to correct the affiliations and conflict of interest in the
      publication of the original article. The corrected details are given below for
      your reading.

PMID- 29214362
TI  - Complete nucleotide sequence of jasmine virus H, a new member of the family
      Tombusviridae.
AB  - Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic
      on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames
      (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2),
      two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid
      protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to
      be a member of the genus Pelarspovirus in the family Tombusviridae.

PMID- 29214360
TI  - Insights into the genome and proteome of Sphingomonas paucimobilis strain 20006FA
      involved in the regulation of polycyclic aromatic hydrocarbon degradation.
AB  - In order to study the mechanisms regulating the phenanthrene degradation pathway
      and the intermediate-metabolite accumulation in strain S. paucimobilis 20006FA,
      we sequenced the genome and compared the genome-based predictions to experimental
      proteomic analyses. Physiological studies indicated that the degradation involved
      the salicylate and protocatechuate pathways, reaching 56.3% after 15 days.
      Furthermore, the strain degraded other polycyclic aromatic hydrocarbons (PAH)
      such as anthracene (13.1%), dibenzothiophene (76.3%), and fluoranthene. The
      intermediate metabolite 1-hydroxy-2-naphthoic acid (HNA) accumulated during
      phenanthrene catabolism and inhibited both bacterial growth and phenanthrene
      degradation, but exogenous-HNA addition did not affect further degradation.
      Genomic analysis predicted 126 putative genes encoding enzymes for all the steps
      of phenanthrene degradation, which loci could also participate in the metabolism
      of other PAH. Proteomic analysis identified enzymes involved in 19 of the 23
      steps needed for the transformation of phenanthrene to trichloroacetic-acid
      intermediates that were upregulated in phenanthrene cultures relative to the
      levels in glucose cultures. Moreover, the protein-induction pattern was temporal,
      varying between 24 and 96 h during phenanthrene degradation, with most catabolic
      proteins being overexpressed at 96 h-e. g., the biphenyl dioxygenase and a
      multispecies (2Fe-2S)-binding protein. These results provided the first clues
      about regulation of expression of phenanthrene degradative enzymes in strain
      20006FA and enabled an elucidation of the metabolic pathway utilized by the
      bacterium. To our knowledge the present work represents the first investigation
      of genomic, proteomic, and physiological studies of a PAH-degrading Sphingomonas
      strain.

PMID- 29214365
TI  - Profiling differential microRNA expression between in situ, infiltrative and
      lympho-vascular space invasive breast cancer: a pilot study.
AB  - Ductal carcinoma in situ (DCIS), invasive breast cancer (IBC) and lympho-vascular
      invasion (LVI) represent distinct stages in breast cancer progression with
      different clinical implications. Altered microRNA (miRNA) expression may play a
      role in mediating the progression of DCIS to IBC and LVI. The aim of this pilot
      study was to investigate whether differential miRNA expression could play a role
      in breast cancer progression. Cancer cells from DCIS, IBC and LVI were
      microdissected from formalin fixed paraffin embedded (FFPE) tissue of five breast
      cancer samples. MiRNA profiling of extracted RNA was performed using the
      TaqMan(r) Array Human MicroRNA Cards A and B v3.0. Candidate miRNAs and gene
      targets were validated by qPCR. 3D culture of MCF10A, MCF10DCIS.com and T47D
      cells were used as models for normal, DCIS and IBC. Immunohistochemistry of
      candidate genes was performed on FFPE 3D cell cultures as well as on tissue
      microarray which included cores of DCIS and IBC samples. MiR-150, miR-126 and miR
      155 were found to be more highly expressed in IBC and LVI compared to DCIS. Gene
      targets of these miRNAs, RhoA, PEG10 and MYB, were found to be more highly
      expressed in DCIS compared to IBC by qPCR and in MCF10A and MCF10DCIS.com cells
      compared to T47D cells by immunohistochemistry. There was no difference in
      intensity of staining of RhoA by immunohistochemistry in DCIS versus IBC samples
      on tissue microarray. In this pilot study, we found evidence to support a
      potential role for variation in miRNA levels in the transition from DCIS to IBC.

PMID- 29214364
TI  - Diverticular colovesical fistula: What should we really be doing?
AB  - BACKGROUND: Colovesical fistula secondary to diverticular disease is increasing
      in incidence. Presentation and severity may differ, but a common management
      strategy may be applied. The aim of this study is to evaluate the characteristics
      and perioperative management of patients with colovesical fistulae and determine
      optimal management. METHODS: From 2003 to 2012, all charts of surgical patients
      with diverticular colovesical fistulae at two different institutions were
      reviewed. Patient and presentation characteristics and perioperative management
      and outcomes were recorded. Patient groups with early and late catheter removal
      (< 8 and >= 8 days) were compared with significance level set at p < 0.05.
      RESULTS: Seventy-eight patient charts were reviewed. The mean duration of
      symptoms was 7.5 months. Laparoscopic assisted surgery was carried out in 35% of
      patients. Complex bladder repair was performed in 27%. Mean length of stay was 8
      days. Mean urinary catheter duration was 13 days. Seventy percent of patients
      underwent postoperative cystogram, with 4% positive for extravasation. Patients
      with early catheter removal were significantly older, more likely to have
      received intraoperative methylene blue instillation, and less likely to have had
      a complex bladder repair (p < 0.05). Complication rate, length of stay,
      postoperative cystography, and stent use were similar for both catheter removal
      groups. CONCLUSIONS: Intraoperative methylene blue bladder instillation should be
      utilized to limit unnecessary bladder repairs. In the setting of negative
      methylene blue extravasation, surgeons may confidently remove urinary catheters
      in 7 days or less, in some cases as early as 48 h. In complex bladder repairs,
      cystogram is still an important adjunct, with those patients with negative
      studies benefiting from catheter removal at 7 days or less.

PMID- 29214366
TI  - Two new Sporothrix species from Protea flower heads in South African Grassland
      and Savanna.
AB  - The inflorescences and infructescences of African Protea trees provide habitat
      for a large diversity of Sporothrix species. Here we describe two additional
      members, Sporothrix nsini sp. nov. and Sporothrix smangaliso sp. nov., that are
      associated with the infructescences of various Protea species from grasslands and
      savannas in the KwaZulu-Natal, North-West, Gauteng and Mpumalanga provinces of
      South Africa. Their description raises the number of described Protea-associated
      Sporothrix species to twelve. S. smangaliso sp. nov. is distantly related to
      other Protea-associated species and, in phylogenies using multiple markers (ITS,
      beta-tubulin and calmodulin), groups with taxa such as Sporothrix bragantina from
      Brazil and Sporothrix curviconia from the Ivory Coast. S. nsini sp. nov. resolved
      as sister to a clade containing four other Protea-associated species within the
      Sporothrix stenoceras complex. S. nsini sp. nov. was collected from within the
      same infructescences of Protea caffra that also contained the closely related S.
      africana and S. protearum. This highlights the need to study and understand the
      factors that influence host selection and speciation of Sporothrix in this
      atypical niche.

PMID- 29214367
TI  - Subtercola vilae sp. nov., a novel actinobacterium from an extremely high
      altitude cold volcano lake in Chile.
AB  - A novel actinobacterium, strain DB165T, was isolated from cold waters of
      Llullaillaco Volcano Lake (6170 m asl) in Chile. Phylogenetic analysis based on
      16S rRNA gene sequences identified strain DB165T as belonging to the genus
      Subtercola in the family Microbacteriaceae, sharing 97.4% of sequence similarity
      with Subtercola frigoramans DSM 13057T, 96.7% with Subtercola lobariae DSM
      103962T, and 96.1% with Subtercola boreus DSM 13056T. The cells were observed to
      be Gram-positive, form rods with irregular morphology, and to grow best at 10-15 
      degrees C, pH 7 and in the absence of NaCl. The cross-linkage between the amino
      acids in its peptidoglycan is type B2gamma; 2,4-diaminobutyric acid is the
      diagnostic diamino acid; the major respiratory quinones are MK-9 and MK-10; and
      the polar lipids consist of phosphatidylglycerol, diphosphatidylglycerol, 5
      glycolipids, 2 phospholipids and 5 additional polar lipids. The fatty acid
      profile of DB165T (5% >) contains iso-C14:0, iso-C16:0, anteiso-C15:0, anteiso
      C17:0, and the dimethylacetal iso-C16:0 DMA. The genomic DNA G+C content of
      strain DB165T was determined to be 65 mol%. Based on the phylogenetic,
      phenotypic, and chemotaxonomic analyses presented in this study, strain DB165T (=
      DSM 105013T = JCM 32044T) represents a new species in the genus Subtercola, for
      which the name Subtercola vilae sp. nov. is proposed.

PMID- 29214368
TI  - Renal pharmacists' perceptions and current practices of assessing medication
      adherence in dialysis patients.
AB  - : Background Medication nonadherence is a major problem in chronic kidney failure
      patients undergoing dialysis. Pharmacists play a vital role in improving
      medication-related patient outcomes, reducing drug-related problems, and
      improving medication adherence. However, little is known about how pharmacists
      assess medication adherence in dialysis patients. Objective To measure
      pharmacists' perceptions, current practices, and barriers to assessing adherence
      in dialysis patients. Setting Australian renal-specialised pharmacists. Method An
      online survey was conducted between March and May 2016. Survey included five
      psychometric scales measuring perceived prevalence, contributors, effective
      methods, barriers, and confidence to assess adherence on a 10-point Likert scale
      (1 = strongly disagree; 10 = strongly agree). Current practices were identified
      using a 4-point graded response (1 = do not practice; 4 = practice for all). MAIN
      OUTCOME MEASURE: Perception scores, scale reliability, and responses to current
      practices questionnaire. Results 41 pharmacists completed the survey (response
      rate, 91.1%). The majority (91.9%, n = 34; median = 8.0) agreed patients were
      nonadherent to medication. Time constraints (43.8%, n = 14) and hospital support
      (31.3%, n = 10) were perceived as barriers to assessment. Objective blood
      monitoring was frequently used to determine nonadherence (57.1%, n = 16), whereas
      subjective interviews were rarely conducted (27.6%, n = 8). Though all
      pharmacists support the presence of dedicated pharmacist for assessing adherence
      (100.0%, n = 33), only 24.2% were actually performing this function. Conclusion
      Pharmacists were rarely assigned for adherence assessment in dialysis settings.
      Established self-report methods were under-utilised compared to objective
      methods. Future research should investigate the effectiveness of pharmacists'
      involvement in facilitating adherence promotion and early identification of
      medication-related issues in dialysis patients.

PMID- 29214369
TI  - Ginkgolide K promotes the clearance of A53T mutation alpha-synuclein in SH-SY5Y
      cells.
AB  - Alpha-synuclein (alpha-syn) is associated to Parkinson's disease (PD). The
      aggregated form of alpha-syn has potential neurotoxicity. Thus, the clearance of
      alpha-syn aggregation is a plausible strategy to delay disease progression of PD.
      In our study, we found that the treatment of Ginkgolide B (GB) and Ginkgolide K
      (GK) reduced cell death, and enhanced cell proliferation in SH-SY5Y cells, which
      overexpressed A53T mutant alpha-syn. Surprisingly, GK, but not GB, promoted the
      clearance of A53T alpha-syn, which can be abolished by autophagy inhibitor 3
      methyladenine, indicating that GK-induced autophagy intervened in the clearance
      of A53T alpha-syn. However, GK did not affect the NEDD4 that belongs to the
      ubiquitin ligase in the endosomal-lysosomal pathway. Furthermore, GK treatment
      inhibited the p-NF-kB/p65 and induced the PI3K, BDNF, and PSD-95. Taken together,
      GK increased the clearance of alpha-syn, reduced cell death, and triggered
      complex crosstalk between different signaling pathways. Although our results show
      a potentially new therapeutic candidate for PD, the details of this mechanism
      need to be further identified.

PMID- 29214370
TI  - Lumbar intervertebral disc allograft transplantation: the revascularisation
      pattern.
AB  - PURPOSE: Fresh frozen intervertebral disc allograft transplantation has been
      reported to be a viable treatment option for advanced degenerative disc diseases,
      but rapid degeneration of the postoperative allograft was found. Loss of nutrient
      supply is believed to be the most likely inducer because the disc allografts have
      to endure in an ischaemic environment until the nutrient pathway is re
      established. The aim of this study was to focus on the revascularisation of the
      disc allograft after transplantation in goats. METHODS: Twenty male goats were
      used in this study. Intervertebral disc allograft transplantation was performed
      at L4/L5. Groups of five goats were killed at 1.5, 6 and 12 m postoperatively,
      respectively. The transplanted segments were harvested, fixed, sagittally cut and
      decalcified for H&E staining and immunochemistry to observe the blood vessel
      formation at the endplates, anterior outer annulus, posterior outer annulus,
      inner annulus and the nucleus. The blood vessel density and the sectional vessel
      area were measured. RESULTS: Blood vessels were first found in the marrow space
      of the bony endplate and the outer annulus at 1.5 month postoperatively. Then,
      they were able to penetrate to reach the cartilaginous endplate and the inner
      annulus after 6 months. Interestingly, the endplate area possessed the most
      abundant blood vessels, with the highest level of vessel density and area at the
      final follow-up. None of these newly formed vessels invaded the nucleus during
      the observation period. CONCLUSIONS: Revascularisation of the postoperative disc
      allograft has been determined, but its pattern was different from that in adult
      normal discs, suggesting that the typical nutrient diffusion pattern may be
      affected after transplantation.

PMID- 29214371
TI  - Biomechanical investigation of lumbar hybrid stabilization in two-level posterior
      instrumentation.
AB  - PURPOSE: Hybrid stabilization with a dynamic implant has been suggested to avoid
      adjacent segment disease by creating a smoother transition zone from the
      instrumented segments to the untreated levels above. This study aims to
      characterize the transition zones of two-level posterior instrumentation
      strategies for elucidating biomechanical differences between rigid fixation and
      the hybrid stabilization approach with a pedicle screw-based dynamic implant.
      METHODS: Eight human lumbar spines (L1-5) were loaded in a spine tester with pure
      moments of 7.5 Nm and with a hybrid loading protocol. The range of motion (ROM)
      of all segments for both loading protocols was evaluated and normalized to the
      native ROM. RESULTS: For pure moment loading, ROM of the segments cranial to both
      instrumentations were not affected by the type of instrumentation (p > 0.5). The
      dynamic instrumentation in L3-4 reduced the ROM compared to intact (p < 0.05) but
      allowed more motion than the rigid fixation of the same segment (p < 0.05). Under
      hybrid loading testing, the cranial segments (L1-2, L2-3) had a significant
      higher ROM for both instrumentations compared to the intact (p < 0.05). Comparing
      the two instrumentations with each other, the rigid fixation resulted in a higher
      increased ROM of L1-2 and L2-3 than hybrid stabilization. CONCLUSIONS: Regardless
      of the implant, two-level posterior instrumentation was accompanied by a
      considerable amount of compensatory movement in the cranial untreated segments
      under the hybrid protocol. Hybrid stabilization, however, showed a significant
      reduction of this compensatory movement in comparison to rigid fixation. These
      results could support the surgical strategy of hybrid stabilization, whereas the
      concept of topping-off, including a healthy segment, is discouraged.

PMID- 29214373
TI  - Utilization of breast cancer screening with magnetic resonance imaging in
      community practice.
AB  - BACKGROUND: Breast cancer screening with magnetic resonance imaging (MRI) may be
      a useful adjunct to screening mammography in high-risk women, but MRI uptake may
      be increasing rapidly among low- and average-risk women for whom benefits are
      unestablished. Comparatively little is known about use of screening MRI in
      community practice. OBJECTIVE: To assess relative utilization of MRI among women
      who do and do not meet professional society guidelines for supplemental
      screening, and describe utilization according to breast cancer risk indications.
      DESIGN: Prospective cohort study conducted between 2007 and 2014. PARTICIPANTS:
      In five regional imaging registries participating in the Breast Cancer
      Surveillance Consortium (BCSC), 348,955 women received a screening mammogram, of
      whom 1499 underwent screening MRI. MAIN MEASURES: Lifetime breast cancer risk (<
      20% or >= 20%) estimated by family history of two or more first-degree relatives,
      and Gail model risk estimates. Breast Imaging Reporting and Data System breast
      density and benign breast diseases also were assessed. Relative risks (RR) for
      undergoing screening MRI were estimated using Poisson regression. KEY RESULTS:
      Among women with < 20% lifetime risk, which does not meet professional guidelines
      for supplementary MRI screening, and no first-degree breast cancer family
      history, screening MRI utilization was elevated among those with extremely dense
      breasts [RR 2.2; 95% confidence interval (CI) 1.7-2.8] relative to those with
      scattered fibroglandular densities and among women with atypia (RR 7.4; 95% CI
      3.9-14.3.) or lobular carcinoma in situ (RR 33.1; 95% CI 18.0-60.9) relative to
      women with non-proliferative disease. Approximately 82.9% (95% CI 80.8%-84.7%) of
      screening MRIs occurred among women who did not meet professional guidelines and
      35.5% (95% CI 33.1-37.9%) among women considered at low-to-average breast cancer
      risk. CONCLUSION: Utilization of screening MRI in community settings is not
      consistent with current professional guidelines and the goal of delivery of high
      value care.

PMID- 29214372
TI  - A Review of the Clinical Utility of Systematic Behavioral Observations in
      Attention Deficit Hyperactivity Disorder (ADHD).
AB  - This review evaluates the clinical utility of tools for systematic behavioral
      observation in different settings for children and adolescents with ADHD. A
      comprehensive search yielded 135 relevant results since 1990. Observations from
      naturalistic settings were grouped into observations of classroom behavior (n =
      58) and of social interactions (n = 25). Laboratory observations were subdivided
      into four contexts: independent play (n = 9), test session (n = 27), parent
      interaction (n = 11), and peer interaction (n = 5). Clinically relevant aspects
      of reliability and validity of employed instruments are reviewed. The results
      confirm the usefulness of systematic observations. However, no procedure can be
      recommended as a stand-alone diagnostic method. Psychometric properties are often
      unsatisfactory, which reduces the validity of observational methods, particularly
      for measuring treatment outcome. Further efforts are needed to improve the
      specificity of observational methods with regard to the discrimination of
      comorbidities and other disorders.

PMID- 29214374
TI  - Serum Antioxidant Parameters are Significantly Increased in Patients with Type 2
      Diabetes Mellitus after Consumption of Chinese Propolis: A Randomized Controlled
      Trial Based on Fasting Serum Glucose Level.
AB  - INTRODUCTION: Propolis is a natural product with many biological activities. The
      present study was designed to evaluate the effects of Chinese propolis on glucose
      metabolism, antioxidant function, and inflammatory cytokines in patients with
      type 2 diabetes mellitus (T2DM). METHODS: In the 18-week study, recruited T2DM
      patients were randomly divided into a Chinese propolis group (900 mg/day) (n =
      31) and a control group (n = 30) according to fasting serum glucose levels at
      baseline. RESULTS: At the end of the study, no significant difference was found
      between the groups in serum glucose, glycosylated hemoglobin, insulin, aldose
      reductase, or adiponectin. However, serum GSH, flavonoids, and polyphenols were
      significantly increased, and serum lactate dehydrogenase activity was
      significantly reduced in the Chinese propolis group. Meanwhile, serum IL-6 was
      significantly increased in the Chinese propolis group. CONCLUSION: Chinese
      propolis is effective at improving antioxidant function in T2DM patients, partly
      by increasing serum antioxidant parameters.

PMID- 29214375
TI  - Review: surgical treatment of giant coronary aneurysms in pediatric patients with
      Kawasaki disease.
AB  - In Kawasaki disease (KD), giant coronary aneurysms in the proximal segments of
      the coronary arteries have long been among the serious complications associated
      with acute myocardial infarction. To treat myocardial ischemia in children,
      Kitamura et al. first performed coronary artery bypass grafting in a pediatric
      patient using an autologous saphenous vein. In the early 1980s, they began to use
      the internal thoracic artery (ITA) as a bypass graft to the left anterior
      descending artery, which later was proven to improve long-term life expectancy
      with its favorable long-term patency, as well as growth potential. Thus, the
      excellent characteristics of the ITA have come to be widely known among pediatric
      cardiac surgeons, and a growing number of coronary bypass surgery procedures
      using the ITA are now being performed worldwide. Although a longer follow-up with
      more patients is necessary, downsizing reconstructive procedure may be a
      treatment of choice for giant aneurysms of non-LAD territories to improve
      coronary circulation. The efficacy of surgical treatment for giant coronary
      aneurysms in pediatric patients with Kawasaki disease is now well established.
      Pediatric coronary artery bypass grafting using the ITA, either single or
      bilateral, can be safe not only for patients with Kawasaki coronary disease but
      also for infants with congenital coronary lesions.

PMID- 29214376
TI  - Polymer-infiltrated ceramic CAD/CAM inlays and partial coverage restorations: 3
      year results of a prospective clinical study over 5 years.
AB  - OBJECTIVE: The aim of this prospective clinical 5-year study was to evaluate the
      long-term behavior of monolithic computer-aided design and computer-aided
      manufacturing (CAD/CAM)-fabricated minimally invasive polymer-infiltrated ceramic
      network (PICN) inlays and partial coverage restorations (PCR). MATERIAL AND
      METHODS: Posterior teeth of 47 patients were restored with 103 restorations (45
      inlays, 58 PCRs). After defect-oriented preparations, monolithic PICN
      restorations of VITA Enamic were fabricated with a CAD/CAM system (inEoS
      blue/CEREC inLab MCXL) and adhesively bonded (Variolink II). Clinical
      reevaluations were so far performed at baseline and 6, 12, 24, and 36 months
      after insertion according to modified United States Public Health Service (USPHS)
      criteria. Absolute failures were demonstrated by Kaplan-Meier survival rate and
      relative failures by Kaplan-Meier success rate. A logistic regression model was
      adjusted for modified USPHS criteria to investigate time and restoration effects
      (p < 0.05). RESULTS: After an observation time of 3 years, survival rates were
      97.4% for inlays and 95.6% for PCRs. Three restorations had to be replaced due to
      clinically unacceptable fractures. Secondary caries and debonding were not
      observed. The 3-year Kaplan-Meier success rate was 84.8% for inlays and 82.4% for
      PCRs. The decrease in marginal adaption (p = 0.0005), increase in marginal
      discoloration (p < 0.0001), and surface roughness (p = 0.0005) over time were
      significant. Color match and anatomic form were excellent. No significant
      differences were found between both types of restorations for survival (p =
      0.716) and success rate (p = 0.431). CONCLUSIONS: Minimally invasive PICN
      restorations showed a favorable clinical performance over an observation period
      of 36 months. However, clinical long-term data have to be awaited. CLINICAL
      RELEVANCE: PICN restorations are a suitable treatment option for posterior inlays
      and PCRs.

PMID- 29214377
TI  - Validation of a new experimental model of extrusive luxation on maxillary molars
      of rats: a histological study.
AB  - BACKGROUND/AIM: The aim of this study was to test and validate a new model of
      extrusive luxation trauma on maxillary first molars of rats. MATERIAL AND
      METHODS: Forty adult male rats (Rattus norvegicus albinus, Wistar; weight = 230
      250 g), 45 days old, were divided into eight groups (n = 5): control groups, in
      which animals were not subjected to any procedure and waited 1 day (GC1D) or 3
      days (GC3D) for euthanasia, and experimental groups, in which animals were
      subjected to forces of 1100cN, 1300cN, or 1500cN and waited 1 or 3 days for
      euthanasia (GT1100/1D, GT1100/3D, GT1300/1D, GT1300/3D, GT1500/1D, GT1500/3D). In
      animals of the experimental groups, trauma was produced by an extrusive force in
      maxillary first right molars. Four-micrometer serial cuts stained with
      hematoxylin and eosin (HE) were made. Descriptive microscopic analysis of first
      upper right molar and semi-quantitative analysis (scores 1 to 4) of intensity of
      acute and chronic inflammation and vascular changes in the periodontal ligament
      and active and inactive external root resorption were conducted. The distribution
      of scores in the groups was compared using the Freeman-Halton extension of
      Fisher's exact test. The significance level was 5%. RESULTS: It was observed that
      vascular disorders (bleeding) on the periodontal ligament became more evident
      with increasing extrusive force. CONCLUSIONS: This new method was capable of
      generating histological changes, proving its secure application in this research
      area. The 1500cN force produced more damage on the periodontal ligament. CLINICAL
      RELEVANCE: The validation of a new experimental method can produce more reliable
      evidence in further research.

PMID- 29214378
TI  - The effectiveness of two types of MADS for OSA therapy.
AB  - OBJECTIVES: The purpose of this study was to determine differences in
      effectiveness between two types of mandibular advancement device (MAD). MATERIAL
      AND METHODS: In this retrospective, cohort study, the two devices used were MAD
      type "Somnodent-Flex" (MAD 1) and MAD type "Herbst" (MAD 2). One hundred thirty
      seven patients participated in this study, 67 patients were treated with MAD 1,
      and 70 patients with MAD 2. The indication MAD with obstructive sleep apnea (OSA)
      is based on a polysomnography test, in accordance with the CBO guidelines. The
      effectiveness of MAD therapy can be determined by a second polysomnography test
      (with the MAD in situ). The apnea-hypopnea index (AHI) is registered during the
      first and the second polysomnography test. Changes in these values determine the
      effectiveness. RESULTS: A significant decrease in AHI was found regarding T1 and
      T2 for both the MADs: F (1, 134) = 140,850, p < 0,001. The mean differences of
      both the MADs turned out to correlate to T1. After correcting for this
      covariance, there was no significant difference between the two MAD devices
      regarding the AHI value: F (1, 134) = 1160, p = 0,283. CONCLUSIONS: The results
      of the present study show no significant difference in effectiveness between MAD
      1 and MAD 2 in respect to the AHI value. CLINICAL RELEVANCE: Since 2012,
      healthcare insurance companies in the Netherlands refunds MAD type "Somnodent"
      used for treatment of sleep apnea. It is important to investigate if this type of
      MAD is as more effective or less effective as other types of MADs. If research
      points out that other MADs are more effective in reducing the sleep apnea, refund
      policies have to be adapted.

PMID- 29214379
TI  - Dual Contribution of Mesenchymal Stem Cells Employed for Tissue Engineering of
      Peripheral Nerves: Trophic Activity and Differentiation into Connective-Tissue
      Cells.
AB  - Adult peripheral nerves in vertebrates can regrow their axons and re-establish
      function after crush lesion. However, when there is extensive loss of a nerve
      segment, due to an accident or compressive damage caused by tumors, regeneration
      is strongly impaired. In order to overcome this problem, bioengineering
      strategies have been employed, using biomaterials formed by key cell types
      combined with biodegradable polymers. Many of these strategies are successful,
      and regenerated nerve tissue can be observed 12 weeks after the implantation.
      Mesenchymal stem cells (MSCs) are one of the key cell types and the main stem
      cell population experimentally employed for cell therapy and tissue engineering
      of peripheral nerves. The ability of these cells to release a range of different
      small molecules, such as neurotrophins, growth factors and interleukins, has been
      widely described and is a feasible explanation for the improvement of nerve
      regeneration. Moreover, the multipotent capacity of MSCs has been very often
      challenged with demonstrations of pluripotency, which includes differentiation
      into any neural cell type. In this study, we generated a biomaterial formed by
      EGFP-MSCs, constitutively covering microstructured filaments made of poly-epsilon
      caprolactone. This biomaterial was implanted in the sciatic nerve of adult rats,
      replacing a 12-mm segment, inside a silicon tube. Our results showed that six
      weeks after implantation, the MSCs had differentiated into connective-tissue
      cells, but not into neural crest-derived cells such as Schwann cells. Together,
      present findings demonstrated that MSCs can contribute to nerve-tissue
      regeneration, producing trophic factors and differentiating into fibroblasts,
      endothelial and smooth-muscle cells, which compose the connective tissue.

PMID- 29214380
TI  - Differential expression of gibberellin- and abscisic acid-related genes implies
      their roles in the bud activity-dormancy transition of tea plants.
AB  - KEY MESSAGE: Thirty genes involved in GA and ABA metabolism and signalling were
      identified, and the expression profiles indicated that they play crucial roles in
      the bud activity-dormancy transition in tea plants. Gibberellin (GA) and abscisic
      acid (ABA) are fundamental phytohormones that extensively regulate plant growth
      and development, especially bud dormancy and sprouting transition in perennial
      plants. However, there is little information on GA- and ABA-related genes and
      their expression profiles during the activity-dormancy transition in tea plants.
      In the present study, 30 genes involved in the metabolism and signalling pathways
      of GA and ABA were first identified, and their expression patterns in different
      tissues were assessed. Further evaluation of the expression patterns of selected
      genes in response to GA3 and ABA application showed that CsGA3ox, CsGA20ox,
      CsGA2ox, CsZEP and CsNCED transcripts were differentially expressed after
      exogenous treatment. The expression profiles of the studied genes during winter
      dormancy and spring sprouting were investigated, and somewhat diverse expression
      patterns were found for GA- and ABA-related genes. This diversity was associated
      with the bud activity-dormancy cycle of tea plants. These results indicate that
      the genes involved in the metabolism and signalling of GA and ABA are important
      for regulating the bud activity-dormancy transition in tea plants.

PMID- 29214381
TI  - Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy
      outcome: a prospective observational cohort study.
AB  - PURPOSE: Cox-2-inhibitors (coxibs) are not recommended in pregnancy but early
      exposure may occur, for instance in unplanned pregnancies. Experience in
      pregnancy is limited leading to concerns in patients and their health care
      providers. Therefore, further data on coxibs and their effects on embryogenesis
      are needed. METHODS: This observational cohort study evaluates pregnancies
      ascertained in Germany during the study period from January 2000 to January 2016.
      A cohort of 174 women exposed to coxibs in the first trimester was compared to a
      randomly selected cohort of 521 women without exposure to coxibs, other
      nonsteroidal anti-inflammatory drugs or known teratogens. RESULTS: The overall
      rate of major birth defects was not significantly increased in the study cohort
      (2.9 vs. 2.7%, OR 1.08, 95% CI 0.34-3.42; OR adjusted 0.96, 95% CI 0.28-3.26).
      The cumulative incidence of spontaneous abortions was nonsignificantly lower in
      the exposed cohort (14.3 vs. 20.0%; HR, 0.90, 95% CI 0.51-1.58; HR adjusted,
      0.87; 95% CI, 0.49-1.56). Elective terminations of pregnancies (ETOP), mainly for
      'social' reasons, were more frequent in the coxib cohort (17.5 vs. 7.0%, HR,
      2.31; 95% CI, 1.26-4.24; HR adjusted 2.12, 95% CI 1.13-3.97). CONCLUSIONS: Our
      study results support the assumption that coxibs are not major teratogens.
      Considering the still limited evidence basis on coxib exposure during pregnancy,
      well-established alternatives should be preferred.

PMID- 29214382
TI  - Bleeding in primary shoulder arthroplasty.
AB  - INTRODUCTION: The aim of this investigation was to analyse "total blood loss"
      (TBL), "blood transfusion rate" (BT) and the "amount of transfused blood units"
      (BU) between the different primary shoulder arthroplasty (SA) types: reverse,
      anatomical and stemless. Only primary SA was included. Further goal was to
      identify risk factors for TBL, amount of BU and BT rate. METHODS: A retrospective
      charts analysis of patients who received primary SA for degenerative shoulder
      pathology in our institution between 2004 and 2016 was performed. The demographic
      data, co-morbidities, haemoglobin and hematocrit level, BT rate, amount of
      transfused BU etc. were collected. TBL was estimated. Linear regression, log
      linear poisson regression and logistic regression were used to compare the
      outcomes TBL, amount of transfused BU and BT rate, respectively, between
      different prosthesis types. RESULTS: Of 278 patients included in this study 209
      received reverse, 57 anatomical and 12 stemless SA. Mean TBL was 392.7 ml in
      reverse, 394.6 ml in anatomical and 298.3 ml in stemless SA. The BT rate and mean
      amount of BU were, respectively, 14.4% and 0.32 in reverse and 8.77% and 0.23 in
      anatomical SA. None of the patients with stemless arthroplasty received BT.
      Significant risk factors for elevated TBL are operation time, higher BMI, male
      sex. Significant risk parameters for BT and higher amount of transfused BU are
      low BMI, cemented arthroplasty, coronary heart disease, ASA score > 2 and
      previous therapy with vitamin K antagonists. CONCLUSION: Although there were
      little differences between the blood transfusion rates in reverse vs. anatomical
      arthroplasty, there was no difference in total blood loss between these different
      prosthesis types. None of the patients with stemless arthroplasty received blood
      transfusion. There are various risk factors affecting total blood loss and blood
      transfusion rate. However, risk parameters influencing blood transfusion may be
      different to them affecting total blood loss.

PMID- 29214383
TI  - Evaluation of the effectiveness and patients' contentment with transanal
      haemorrhoidal artery dearterialisation and mucopexy (THD) for treatment of
      haemorrhoidal disease: a 6-year study.
AB  - INTRODUCTION: With high incidence of haemorrhoidal disease and significant
      complication rates of traditional haemorrhoidectomy procedures, transanal
      haemorrhoidal artery ligation and mucopexy (THD) emerges as a minimally invasive
      procedure with superior results. However, it is crucial that effectiveness of
      results and patient satisfaction be gauged based on post-operative experience,
      symptomology and recurrence. AIM: Our aim is to provide a long-term analysis of
      efficacy and patient's satisfaction for the procedure, for the largest patient
      population, in correlation to presenting symptoms and degree of haemorrhoids.
      METHOD: A prospective study was conducted for all the patients (324) that
      underwent THD between 2011 and 2016 in Naas General Hospital. The assessment was
      done for postoperative complications, symptoms pre- and postoperatively and
      patients' satisfaction rating. Clinical follow-up was done after 6 weeks and long
      term follow-up by standardized questionnaire filled by telephonic clinic.
      RESULTS: Of the 324 patients who underwent surgery, 256 (79.0%) participated in
      the study. There were 119 (46.5%) males and 137 (53.5%) females. The average age
      of patients was 48.40 years (17-82). Two hundred and fifteen (84.0%) patients had
      no recurrence. Forty-one (16.0%) had recurrence requiring further treatment.
      There was statistically significant higher recurrence in patients with grade 3
      and 4 haemorrhoids and per-rectal bleeding (p < 0.05) while there was no
      statistically significant recurrence for age, gender, sedentary lifestyle and
      constipation/pruritus. Two hundred and twenty-four (87.5%) patients were
      completely satisfied from the procedure and highly recommend the procedure.
      CONCLUSION: THD is a comparably pain-free procedure with improved results that
      prides in higher long-term satisfaction, minimal recurrence and fewer
      complications, in comparison to other surgical modalities.

PMID- 29214385
TI  - Sealing Effects on the Storage Stability of the Cyanide Antidotal Candidate,
      Dimethyl Trisulfide.
AB  - BACKGROUND: Dimethyl trisulfide (DMTS) is a highly lipid-soluble cyanide (CN)
      antidote candidate molecule. In prior studies with various US FDA-approved co
      solvents, surfactants, and their combinations, aqueous solutions containing 15%
      polysorbate 80 (Poly80) were found to effectively solubilize DMTS in formulations
      for intramuscular administration. However, DMTS formulated in 15% aqueous Poly80
      solutions showed gradual losses over time when stored in vials with septum-based
      seals. OBJECTIVE: The present study tested whether storing DMTS formulations in
      hermetically sealed glass ampules could mitigate storage losses. METHODS: Samples
      consisted of 1-mL aliquots of a 50 mg/ml stock solution of DMTS in 15% aqueous
      Poly80. The control samples were stored using a vial-within-a-vial system-the
      inner and outer vials were sealed respectively, with a snap cap, and with a
      crimped septum. The hermetically sealed test samples were stored in fire-sealed
      glass ampules. The DMTS content was measured by HPLC-UV analysis at specific time
      points over a 100-day period. RESULTS: While the control samples exhibited
      systematic DMTS losses, no DMTS losses were observed from the test samples stored
      in hermetically sealed glass ampules over the 100-day testing period. CONCLUSION:
      DMTS formulated in 15% aqueous Poly80 solution has excellent stability when
      stored in fire-sealed glass ampules and thus has the potential to be effectively
      stored as an intramuscular CN countermeasure for mass casualty scenarios.

PMID- 29214384
TI  - Dispensability of Annual Laboratory Follow-Up After More than 2 Years of Valproic
      Acid Use: A Systematic Review.
AB  - BACKGROUND: The necessity of annual laboratory follow-up in patients treated with
      valproic acid (VPA) is controversial. OBJECTIVE: We investigated the need for
      annual laboratory follow-up of liver enzymes, electrolytes, and full blood count
      (FBC) in patients treated with VPA. PATIENTS AND METHODS: A systematic search in
      Evidence-Based Medicine Reviews (EBMR), MEDLINE, and EMBASE was undertaken in
      December 2016 to identify all published articles investigating or citing valproic
      acid, liver function disorders, electrolyte disorders, and FBC deviations.
      RESULTS: This review included 108 articles. As the number of participants and
      duration of the study was not adequate in most studies to detect rare adverse
      events, studies did not demonstrate a clear prevalence of hepatotoxicity. While a
      transient increase of transaminases is common and seldom harmful, severe
      hepatotoxicity is a rare phenomenon and is not prevented by routine laboratory
      monitoring. VPA had no relevant effect on serum calcium, sodium, potassium, and
      albumin. The prevalence of FBC varied from 0.6 to 27.8%, occurred mostly in the
      first 2 years of therapy, and was usually asymptomatic. CONCLUSIONS: Long-term
      monitoring in VPA treatment is only necessary when there have been dose
      adjustments, co-medication switches, or co-morbidity. In uncomplicated cases,
      annual laboratory follow-up may be discontinued after 2 years of VPA treatment.
      Encouraging patients to be vigilant is more effective in the detection of
      hepatotoxicity than laboratory testing. Follow-up of FBC at 3-6 months, 1 year,
      and 2 years after start or after a dose increase of VPA or interacting medication
      is sufficient.

PMID- 29214387
TI  - Dealing with difference: a scoping review of psychotherapeutic interventions with
      unaccompanied refugee minors.
AB  - Unaccompanied refugee minors (URMs) are a population at risk for developing
      mental problems, post-traumatic stress disorder, anxiety, and/or depression.
      Therapists working with URMs often have to overcome language and cultural
      barriers, while taking into account these young people's specific needs. A
      growing literature describes a wide range of interventions designed to reduce
      psychopathologies and improve well-being. We summarized the different
      interventions used with URMs to get an overview of techniques used for reducing
      psychopathologies and difficulties of URMs and to give recommendations to help
      professionals. We searched eight databases for articles and books, imposing no
      restrictions on publication date or geographical region, and using English and
      French keywords. We included all studies (RCTs, case series, case study) that
      assessed an intervention with one or more URMs. Seventeen studies, reported in
      papers or book chapters, met the criteria for inclusion in our analysis. Only one
      RCT has been conducted with URMs but because of small sample size we cannot
      conclude on its efficacy. Other studies are case series or case studies and
      because of their study design, we cannot conclude whether one intervention is
      superior to others. Further research, with higher level of evidence, is needed to
      determine which types of intervention are most effective when working with URMs.

PMID- 29214388
TI  - Current UK Practices on Health Economics Analysis Plans (HEAPs): Are We Using
      Heaps of Them?

PMID- 29214386
TI  - Improvement rate of patients with severe brain injury during post-acute intensive
      rehabilitation.
AB  - Patients with severe acquired brain injury (SABI) may evolve towards different
      outcomes. The primary aim was to evaluate the clinical evolution of a large
      population of patients with SABI admitted to post-acute rehabilitation from 2001
      to 2016, diagnosed with severe brain injury (GCS <= 8) in the acute phase and a
      coma duration of at least 24 h. The possible changes between the admission time
      to a post-acute rehabilitation hospital and the discharge time were measured by
      means of Glasgow Outcome Scale (GOS), Level of Cognitive Functioning (LCF), and
      Disability Rating Scale (DRS). We also correlated the improvement rate with some
      sociodemographic and clinical features of the individuals with SABI enrolled.
      Data of 890 patients were analyzed (54% TBI, length of stay = 162 +/- 186 days,
      GCS = 7.46 +/- 1.28); time interval from the SABI (OR = 0.246, CI 95% = 0.181 -
      0.333), scores at admission of LCF (OR = 2.243, CI 95% = 1.492 - 3.73), GOS (OR =
      0.138, CI 95% = 0.071 - 0.266), DRS (OR = 0.457, CI 95% = 0.330 - 0.632), and
      etiology (OR = 2.273, CI 95% = 1.676 - 3.084) played a significant role (p <
      0.001, explained variance 69.9%) for improving GOS score. Time interval from the
      SABI to admission in our post-acute rehabilitation ward (OR = 0.300, CI 95% =
      0.179 - 0.501, p < 0.001), length of rehabilitation stay (OR = 2.808, CI 95% =
      1.694 - 4.653, p < 0.001), and etiology (OR = 1.769, CI 95% = 1.095 - 2.857, p =
      0.020) led to a statistically significant improvement in DRS (explained variance
      91%). The most significant predictive factors for the outcome of patients with
      SABI were etiology, time interval from SABI to admission in rehabilitation, and
      length of rehabilitation stay.

PMID- 29214389
TI  - Using Real-World Data in Health Technology Assessment (HTA) Practice: A
      Comparative Study of Five HTA Agencies.
AB  - BACKGROUND: Reimbursement decisions are conventionally based on evidence from
      randomised controlled trials (RCTs), which often have high internal validity but
      low external validity. Real-world data (RWD) may provide complimentary evidence
      for relative effectiveness assessments (REAs) and cost-effectiveness assessments
      (CEAs). This study examines whether RWD is incorporated in health technology
      assessment (HTA) of melanoma drugs by European HTA agencies, as well as
      differences in RWD use between agencies and across time. METHODS: HTA reports
      published between 1 January 2011 and 31 December 2016 were retrieved from
      websites of agencies representing five jurisdictions: England [National Institute
      for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium
      (SMC)], France [Haute Autorite de sante (HAS)], Germany [Institute for Quality
      and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland
      (ZIN)]. A standardized data extraction form was used to extract information on
      RWD inclusion for both REAs and CEAs. RESULTS: Overall, 52 reports were
      retrieved, all of which contained REAs; CEAs were present in 25 of the reports.
      RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma
      prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term
      effectiveness and/or identify drug-related costs. Differences emerged between
      agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on
      prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug
      effectiveness. No visible trend for RWD use in REAs and CEAs over time was
      observed. CONCLUSION: In general, RWD inclusion was higher in CEAs than REAs, and
      was mostly used to estimate melanoma prevalence in REAs or to predict long-term
      effectiveness in CEAs. Differences emerged between agencies' use of RWD; however,
      no visible trends for RWD use over time were observed.

PMID- 29214390
TI  - Changes in motor performance and mental workload during practice of reaching
      movements: a team dynamics perspective.
AB  - Few investigations have examined mental workload during motor practice or
      learning in a context of team dynamics. This study examines the underlying
      cognitive-motor processes of motor practice by assessing the changes in motor
      performance and mental workload during practice of reaching movements.
      Individuals moved a robotic arm to reach targets as fast and as straight as
      possible while satisfying the task requirement of avoiding a collision between
      the end-effector and the workspace limits. Individuals practiced the task either
      alone (HA group) or with a synthetic teammate (HRT group), which regulated the
      effector velocity to help satisfy the task requirements. The findings revealed
      that the performance of both groups improved similarly throughout practice.
      However, when compared to the individuals of the HA group, those in the HRT group
      (1) had a lower risk of collisions, (2) exhibited higher performance consistency,
      and (3) revealed a higher level of mental workload while generally perceiving the
      robotic teammate as interfering with their performance. As the synthetic teammate
      changed the effector velocity in specific regions near the workspace boundaries,
      individuals may have been constrained to learn a piecewise visuomotor map. This
      piecewise map made the task more challenging, which increased mental workload and
      perception of the synthetic teammate as a burden. The examination of both motor
      performance and mental workload revealed a combination of both adaptive and
      maladaptive team dynamics. This work is a first step to examine the human
      cognitive-motor processes underlying motor practice in a context of team dynamics
      and contributes to inform human-robot applications.

PMID- 29214391
TI  - Stroking and tapping the skin: behavioral and electrodermal effects.
AB  - Being caressed represents one of the most typical expressions of affection
      conveyed by touch. Converging evidence suggests that the pleasant perception of
      gentle and slow stroking delivered to the hairy skin is mediated by C-Tactile
      afferents (CTs). While behavioral and neural responses to CT-optimal touch have
      been moderately explored so far, less is known about the autonomic reaction to
      different kinds of touch (both CT-optimal and not). Here, we investigated whether
      physiological arousal varies as a function of the specific tactile stimulation
      provided. Stroking (slow: 3 cm/s 'CT-optimal'; or fast: 30 cm/s) and tapping
      (random or fixed spatial order) stimulations were delivered to the participants'
      forearm with a brush, for durations of 9 or 60 s. Participants' skin conductance
      response (SCR) and level (SCL), as well as subjective evaluations, were recorded.
      The results revealed that being stroked (at both the velocities) induced higher
      SCR and SCL than being tapped. Moreover, while higher SCR was elicited by CT
      suboptimal stroking compared to CT-optimal stroking, SCL was not affected
      differently by CT-optimal touch. No differences were found between the effects of
      9 and 60 s stimulations. Slow stroking was evaluated as the most pleasant,
      relaxing and 'social' type of touch compared to the other tactile stimulations.
      Taken together, these findings shed light on the psychophysiological responses to
      stroking (including CT-optimal touch) and tapping, and contribute to elucidate
      the mechanisms underlying hedonic tactile perception.

PMID- 29214392
TI  - Modulation of specific inhibitory networks in fatigued locomotor muscles of
      healthy males.
AB  - Reduced maximal force capability of skeletal muscle, as a consequence of
      exercise, can be due to peripheral or central fatigue mechanisms. In upper-limb
      muscles, neuromuscular fatigue is concurrent with reduced corticospinal
      excitability and increased inhibition (lengthened corticospinal silent period
      [CSP]; reduced short-interval intracortical inhibition [SICI] ratio). However, it
      is unclear whether these adjustments occur in response to fatiguing exercise of
      locomotor muscles. This study examined the effect of fatiguing, maximal, knee
      extensor exercise on motor cortical excitability and inhibition. Thirteen males
      performed three 30-s maximal, isometric contractions with the dominant knee
      extensors (MVC1, MVC2 and MVC3), separated by 60 s. At the end of, and between
      each MVC, neuromuscular fatigue, corticospinal excitability, CSP and SICI were
      assessed with supramaximal stimulation of the femoral nerve, and motor cortical
      stimulation, respectively. Repeated MVCs caused progressive reductions in MVC (-
      10, - 24 and - 29%, respectively, P <= 0.01), along with significant peripheral
      (reductions in potentiated twitch of - 23, -53 and - 60%, respectively, P <
      0.001) and central (reductions in VA of - 10% and - 13% post-MVC2 and 3,
      respectively, P <= 0.01) fatigue. Following MVC1 corticospinal excitability was
      reduced, and remained depressed thereafter. CSP increased in duration and
      remained longer throughout the protocol; whereas, no change in SICI was observed.
      Repeated, sustained, maximal contractions of the knee-extensors elicited
      substantial peripheral and central fatigue that was accompanied by a concomitant
      reduction in corticospinal excitability. However, divergent responses exist
      between inhibitory networks within the motor cortex, the activity of inhibitory
      networks mediated by GABAB are increased, whereas those mediated by GABAA are
      not.

PMID- 29214393
TI  - Synthesis and analytical characterization of new thiazol-2-(3H)-ones as human
      neutrophil elastase (HNE) inhibitors.
AB  - Human neutrophil elastase (HNE) is a potent serine protease belonging to the
      chymotrypsin family and is involved in a variety of pathologies affecting the
      respiratory system. Thus, compounds able to inhibit HNE proteolytic activity
      could represent effective therapeutics. We present here the synthesis of new
      thiazol-2-(3H)-ones as an elaboration of potent HNE inhibitors with an isoxazol-5
      (2H)-one scaffold that we recently identified. Two-dimensional NMR spectroscopic
      techniques and tandem mass spectrometry allowed us to correctly assign the
      structure of the final compounds arising from both tautomers of the thiazol-2
      (3H)-one nucleus (N-3 of the thiazol-2-(3H)-one and 3-OH of the thiazole). All
      new compounds were tested as HNE inhibitors, and no activity was found at the
      highest concentration used (40 uM), demonstrating that the thiazol-2-(3H)-one is
      not a good scaffold for HNE inhibitors. Molecular modelling experiments indicate
      that the low-energy pose might limit the nucleophilic attack on the endocyclic
      carbonyl group of the thiazolone-based compounds by HNE catalytic Ser195, in
      contrast to isoxazol-5-(2H)-one analogues.

PMID- 29214394
TI  - Serious Adverse Events Associated with Anti-Tumor Necrosis Factor Alpha Agents in
      Pediatric-Onset Inflammatory Bowel Disease and Juvenile Idiopathic Arthritis in A
      Real-Life Setting.
AB  - OBJECTIVES: Anti-tumor necrosis factor alpha (anti-TNF-alpha) agents are
      generally well tolerated, yet they can be associated with serious adverse events
      (SAEs) in a minority of patients. We examined the incidence of SAEs in a
      pediatric referral center for chronic rheumatologic and gastroenterological
      inflammatory disorders. METHODS: Retrospective analysis of SAEs occurring during
      treatment with anti-TNF-alpha agents in patients with juvenile idiopathic
      arthritis (JIA) (n = 78)  or pediatric-onset inflammatory bowel disease (IBD) (n
      = 105) seen at the Institute for Maternal and Child Health IRCCS "Burlo Garofolo"
      in Trieste, Italy, between June 2001 and February 2016. Only SAEs grade 3-5
      according to the Common Terminology Criteria for Adverse Events version 4.03
      and/or requiring definitive therapy discontinuation were reported. RESULTS: Total
      anti-TNF-alpha exposure was 390.5 patient-years (PYs). The overall incidence rate
      of SAEs for etanercept was 4.14/100 PYs. Four patients developed uveitis, two had
      anxiety disorders, one had a serious zoster infection, and one developed TNF
      alpha antagonist-induced lupus-like syndrome (TAILS). The overall incidence rate
      of SAEs for infliximab was 22.49/100 PYs. The most common SAEs were anaphylactoid
      reactions (n = 18), followed by infectious events (n = 9) and TAILS (n = 3). The
      overall incidence rate of SAEs for adalimumab was 4.71/100 PYs (two infectious
      SAEs). No malignancies or deaths were observed. A greater incidence rate of
      infectious SAEs was observed in IBD patients receiving infliximab compared to JIA
      patients receiving etanercept (8.11 vs 0.52 per 100 PYs). CONCLUSIONS: Anti-TNF
      alpha therapy was generally well tolerated. SAEs leading to anti-TNF-alpha
      discontinuation were rare and non-fatal. Infliximab was associated with the
      highest incidence of SAEs. Infectious SAEs were more frequently observed in IBD
      patients treated with infliximab than in JIA patients receiving etanercept.

PMID- 29214396
TI  - Triple management of cubitus valgus deformity complicating neglected nonunion of
      fractures of lateral humeral condyle in children: a case series.
AB  - BACKGROUND: Long standing nonunion of the lateral humeral condyle (LHC) usually
      results in elbow pain and instability with progressive cubitus valgus and tardy
      ulnar neuritis. Surgical treatment of long standing nonunion is still a
      controversial issue due to the reported complications, such as stiffness, loss of
      elbow motion, and avascular necrosis of the LHC fragment. In this study, we
      reported the outcomes of treatment of cubitus valgus deformity in long standing
      nonunion of the LHC in children treated with combined triple management (fixation
      of the nonunion site, dome corrective osteotomy, and anterior transposition of
      ulnar nerve) through a modified para-triceptal approach. METHODS: We evaluated
      ten patients with cubitus valgus deformity more than 20 degrees after neglected
      nonunion of the lateral humeral condyle more than 24 months. Only childern with
      post-operative follow up more than 24 months were included in this study. All
      patients were evaluated clinically, radio logically, and by pre- and post
      operative functional evaluation using Mayo elbow performance score. For
      evaluation of ulnar nerve affection, the Akahori's system was used. RESULTS:
      There were six females and four males with the average age of 7.7 years at
      operation. The left elbow was affected in six patients and the right elbow was
      affected in four patients. The average time between fracture of the LHC and
      operation was 40.3 months with average post-operative follow up of 44.3 months.
      The average carrying angle of the healthy side was 5.5 degrees and pre-operative
      carrying angle of the affected side was 33.5 degrees. The average post-operative
      carrying angle of the affected side was 6.1 degrees. The improvement of the
      carrying angle at the last follow up was found statistically significant (p <
      0.05). All six patients that had pre-operative various degrees of ulnar nerve
      affection had completely improved at last follow up. The osteotomy site united in
      an average time of 43 days, whereas the LHC nonunion site united in an average
      time of 77.2 days. The osteotomy site united in significantly less time than the
      LHC non-union site (p < 0.05). The correlation between time since injury and time
      of union of LHC non-union site was significant (p < 0.05). Post-operative elbow
      range of motion was not changed in five patients, slightly decreased in four
      patients, and increased in one patient. Three patients had an average 6.7 degrees
      (range; 5-10) loss of the last degrees of flexion. One patient developed
      extension lag of 10 degrees. The mean elbow range of motion (ROM) pre-operatively
      was 139 +/- 4.6 degrees while the mean post-operative ROM was 138 +/- 5.3
      degrees. The difference was found to be statistically insignificant (p > 0.05).
      The mean pre-operative Mayo elbow performance score was poor 55 +/- 9.7, four
      patients had fair score, and six had poor score. The mean post-operative Mayo
      elbow performance score was excellent 92.5 +/- 10, six patients had excellent
      score, and four had good score. The improvement of the Mayo score at the last
      follow up was found to be statistically significant (p < 0.05). No intra
      operative complications were recorded during any of the procedures and no patient
      developed a wound or pin track infection post-operatively. At the last follow up,
      none of the patients had developed avascular necrosis of the LHC. CONCLUSION:
      Preservation of the blood supply of the nonunited fragment is the key to
      successful management. This combined technique successfully addresses different
      aspects of the problem simultaneously and provides a durable solution without
      deterioration of the results over time. The para-triceptal approach provided
      excellent exposure of both sides of the elbow with minimal disruption of the
      triceps muscle.

PMID- 29214395
TI  - Pharmacological Management of Hereditary Angioedema with C1-Inhibitor Deficiency
      in Pediatric Patients.
AB  - Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is a form of
      bradykinin-mediated angioedema. It is a rare disorder with an onset during
      childhood in most instances. Therefore, familiarity with the options for the
      management of pediatric cases is indispensable. The recurrent angioedematous
      episodes do not respond to conventional treatments and may evolve into a life
      threatening condition. In view of the recommendations adopted by international
      consensus in 2016, patient management and follow-up should be guided by an
      individualized strategy. During the last decade, various medicinal products with
      novel modes of action and different posology have been developed for the
      treatment of C1-INH-HAE. These drugs either inhibit the release of bradykinin
      (plasma-derived C1-inhibitors, recombinant C1-inhibitors, kallikrein inhibitors)
      or prevent the released bradykinin from binding to its receptor (bradykinin B2
      receptor antagonists). This review summarizes the properties of the medicinal
      products currently available for the treatment of C1-INH-HAE, the indications for
      their use in pediatric patients, and the findings of the clinical trials
      conducted in this patient population. It is concluded by a brief outline of
      future therapeutic options.

PMID- 29214397
TI  - Xanthine oxidase and uric acid as independent predictors of albuminuria in
      patients with diabetes mellitus type 2.
AB  - Xanthine oxidase (XO) is an important enzyme responsible for conversion of purine
      bases to uric acid and represents the major source of reactive oxygen species
      (ROS) production in circulation. Since pathophysiological mechanism of the
      relationship between XO activity and urinary albumin excretion (UAE) rate is not
      well elucidated, we aimed to investigate this association in patients with
      diabetes mellitus type 2 (DM2). In addition, we wanted to examine whether uric
      acid itself plays an independent role in albuminuria onset and progression, or it
      is only mediated through XO activity. A total of 83 patients with DM2 (of them
      56.6% females) were included in this cross-sectional study. Anthropometric,
      biochemical parameters and blood pressure were obtained. Multivariate logistic
      regression analysis showed that uric acid and XO were the independent predictors
      for albuminuria onset in patients with DM2 [odds ratio (OR) 1.015, 95% CI (1.008
      1.028), p = 0.026 and OR 1.015, 95% CI (1.006-1.026), p = 0.040, respectively].
      Rise in uric acid for 1 umol/L enhanced the probability for albuminuria by 1.5%.
      Also, elevation in XO activity for 1 U/L increased the probability for
      albuminuria for 1.5%. A total of 66.7% of variation in UAE could be explained
      with this Model. Both XO and uric acid are independently associated with
      albuminuria in diabetes. Better understanding of pathophysiological relationship
      between oxidative stress and albuminuria could lead to discoveries of best
      pharmacological treatment of XO- and/or uric acid-induced ROS, in order to
      prevent albuminuria onset and progression.

PMID- 29214399
TI  - Preservation of motor maps with increased motor evoked potential amplitude
      threshold in RMT determination.
AB  - OBJECTIVE: Non-invasive pre-surgical mapping of eloquent brain areas with
      navigated transcranial magnetic stimulation (nTMS) is a useful technique linked
      to the improvement of surgical planning and patient outcomes. The stimulator
      output intensity and subsequent resting motor threshold determination (rMT) are
      based on the motor-evoked potential (MEP) elicited in the target muscle with an
      amplitude above a predetermined threshold of 50 MUV. However, a subset of
      patients is unable to achieve complete relaxation in the target muscles,
      resulting in false positives that jeopardize mapping validity with conventional
      MEP determination protocols. Our aim is to explore the feasibility and
      reproducibility of a novel mapping approach that investigates how an increase of
      the MEP amplitude threshold to 300 and 500 MUV affects subsequent motor maps.
      MATERIALS AND METHODS: Seven healthy subjects underwent motor mapping with nTMS.
      RMT was calculated with the conventional methodology in conjunction with
      experimental 300- and 500-MUV MEP amplitude thresholds. Motor mapping was
      performed with 105% of rMT stimulator intensity using the FDI as the target
      muscle. RESULTS: Motor mapping was possible in all patients with both the
      conventional and experimental setups. Motor area maps with a conventional 50-MUV
      threshold showed poor correlation with 300-MUV (alpha = 0.446, p < 0.001) maps,
      but showed excellent consistency with 500-MUV motor area maps (alpha = 0.974, p <
      0.001). MEP latencies were significantly less variable (23 ms for 50 MUV vs. 23.7
      ms for 300 MUV vs. 23.7 ms for 500 MUV, p < 0.001). A slight but significant
      increase of the electric field (EF) value was found (EF: 60.8 V/m vs. 64.8 V/m
      vs. 66 V/m p < 0.001). CONCLUSION: Our study demonstrates the feasibility of
      increasing the MEP detection threshold to 500 MUV in rMT determination and motor
      area mapping with nTMS without losing precision.

PMID- 29214400
TI  - Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan
      on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.
AB  - BACKGROUND: Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains
      one of the major factors contributing to poor overall patient outcome.
      Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads
      to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral
      vasospasm. Losartan is already known to have beneficial effects in stroke models
      and also on several cerebral inflammatory processes. Therefore, the aim of the
      study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction
      after SAH. METHODS: To investigate the effect of losartan on PGF2a-enhanced
      vasoconstriction after SAH, cerebral vasospasm was induced by a double
      haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by
      measurement of the isometric force of basilar artery ring segments in an organ
      bath. RESULTS: PGF2a induced a dose-dependent contraction. After pre-incubation
      with losartan, the maximum contraction (Emax) for sham-operated animals was
      significantly lowered [Emax 6% in losartan 3 * 10-4 molar (M) vs. 56% without
      losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre
      incubated vessels with losartan 3 * 10-4 M on day 3 (d3) as well as on day 5
      (d5). For the vasorelaxative investigations, vessel segments were pre-incubated
      with PFG2a. Cumulative application of losartan completely resolved the pre
      contraction in sham-operated animals (non SAH: 95% relaxation). After SAH,
      losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the
      pre-contraction (d3: 119%). Therefore, a statistically significantly increased
      and earlier relaxation was calculated for all losartan concentrations [Emax
      (d3/d5) and pD2 (d3/d5)] compared with the solvent control group. CONCLUSION: In
      a physiological and pathophysiological setup, losartan reduces a PGF2-induced
      vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be
      integrated in pushing forward further concepts trying to antagonise/prevent
      cerebral vasospasm after SAH.

PMID- 29214401
TI  - Predictors of surgical outcomes for severe cubital tunnel syndrome: a review of
      146 patients.
AB  - BACKGROUND: Full recovery is unlikely for severe cubital tunnel syndrome, and
      prognostic factors remain uncertain. We aimed to identify predictors of surgical
      outcome for these patients. METHODS: One hundred forty-six patients with McGowan
      grade III cubital tunnel syndrome were evaluated retrospectively with a minimum
      follow-up of 2 years. All patients underwent either in situ decompression or
      subcutaneous transposition. The primary outcome measure was postoperative McGowan
      grade. Predictors included age, sex, dominant hand, disease duration, diabetes
      mellitus, smoking, alcohol, surgical procedure, follow-up time and preoperative
      electrophysiological data. Spearman's rank correlation and ordinal logistic
      regression model were used to assess the effect of independent variables on the
      postoperative McGowan grade. RESULTS: At the last follow-up, improvement by at
      least one McGowan grade was reached in 118 cases (80.8%), and complete recovery
      was achieved in 40 hands (27.4%), while 28 extremities (19.2%) remained at grade
      III. Older age [per 10-year increase, odds ratio (OR) 2.10; 95% confidence
      interval (95% CI) 1.55-2.84, p < 0.001], longer disease duration (per 1-year
      increase, OR 1.31; 95% CI 1.16-1.49, p < 0.001), absent sensory nerve conduction
      (OR 2.55; 95% CI 1.25-5.21, p = 0.010) and shorter postoperative follow-up (per 1
      year increase, OR 0.76; 95% CI 0.65-0.90, p = 0.001) were associated with a
      higher postoperative McGowan grade. CONCLUSION: Significant improvement but not
      complete recovery could be expected following in situ decompression or
      subcutaneous transposition for severe cubital tunnel syndrome. Older age, longer
      disease duration, absent sensory nerve conduction and shorter postoperative
      follow-up are independent predictors of worse outcomes.

PMID- 29214402
TI  - Decision-making and neurosurgeons' agreement in the management of aneurysmal
      subarachnoid haemorrhage based on computed tomography angiography.
AB  - BACKGROUND: To determine the neurosurgeon's agreement in aneurysmal subarachnoid
      haemorrhage (aSAH) management with special emphasis on the rater's level of
      experience. A secondary aim was to analyse potential aneurysm variables
      associated with the therapeutic recommendation. METHOD: Basic clinical
      information and admission computed tomography angiography (CTA) images of 30
      consecutive aSAH patients were provided. Twelve neurosurgeons independently
      evaluated aneurysm characteristics and gave recommendations regarding the
      emergency management and aneurysm occlusion therapy. Inter-rater variability and
      predictors of treatment recommendation were evaluated. RESULTS: There was an
      overall moderate agreement in treatment decision [kappa = 0.43; 95% confidence
      interval ((CI), 0.387-0.474] with moderate agreement for surgical (kappa = 0.43;
      95% CI, 0.386-0.479) and endovascular treatment recommendation (kappa = 0.45; 95%
      CI, 0.398-0.49). Agreement on detailed treatment recommendations including clip,
      coil, bypass, stent, flow diverter and ventriculostomy was low to moderate. Inter
      rater agreement did not significantly differ between residents and consultants.
      Middle cerebral artery (MCA) aneurysm location was a positive predictor of
      surgical treatment [odds ratio (OR), 49.57; 95% CI, 10.416-235.865; p < 0.001],
      while patients aged >65 years (OR, 0.12; 95% CI, 0.03-0.0434; p = 0.001),
      fusiform aneurysm type (OR, 0.18; 95% CI, 0.044-0.747; p = 0.018) and
      intracerebral haematoma (ICA) aneurysm location (OR, 0.24; 95% CI, 0.088-0.643; p
      = 0.005) were associated with a recommendation for endovascular treatment.
      CONCLUSIONS: Agreement on aSAH management varies considerably across
      neurosurgeons, while therapeutic decision-making is challenging on an individual
      patient level. However, patients aged >65 years, fusiform aneurysm shape and ICA
      location were associated with endovascular treatment recommendation, while MCA
      aneurysm location remains a surgical domain in the opinion of neurosurgeons
      without formal endovascular training.

PMID- 29214403
TI  - Executive functioning, academic skills, and quality of life in pediatric patients
      with brain tumors post-proton radiation therapy.
AB  - Radiation therapy (RT) is integral in the treatment of pediatric brain tumors;
      however, photon RT (XRT) often results in intellectual decline, executive
      functioning (EF) deficits, academic underachievement/failure, and lower health
      related quality of life (HRQoL). Proton RT (PRT) provides more targeted therapy,
      minimizing damage to the developing brain, yet few studies have examined its
      neuropsychological effects. This study investigated the role of EF in academic
      skills and HRQoL in a sample of children treated with PRT. A mediation model was
      proposed in which academic skills mediated relations between aspects of EF and
      school-based HRQoL (sHRQoL). Sixty-five children (xage = 12.4; 43.9% male)
      treated with PRT completed follow-up neuropsychological testing as part of
      routine care. Measures included assessment of intellectual functioning, EF,
      attention, and academic skills (reading, math, spelling). Parents reported on
      children's EF and attention problems. sHRQoL was assessed via child self-report.
      Children who underwent PRT demonstrated relatively intact intelligence,
      academics, attention, EF, and sHRQoL, but were at risk for reduced processing
      speed. Poorer working memory and processing speed were related to lower sHRQoL.
      Better EF and faster processing speed were associated with better academic
      skills, which were linked to higher sHRQoL. Better working memory was associated
      with better math performance, which was linked to higher sHRQoL; this
      relationship did not hold for reading or spelling. Results highlight the
      importance of EF skills in academic performance and sHRQoL, and the need for
      routine screening of EF deficits and proactive supports. Supports may include
      cognitive rehabilitation and in-class accommodations. Overall, results compare
      favorably to XRT outcomes reported in the literature.

PMID- 29214404
TI  - The 19S proteasome regulates subtelomere silencing and facultative
      heterochromatin formation in fission yeast.
AB  - Accumulating evidence shows that non-proteolytic functions of the proteasome are
      as crucial as its well-known proteolytic function in regulating cellular
      activities. In our recent work, we showed that the 19S proteasome mediates the
      heterochromatin spreading of centromeric heterochromatin in non-proteolytic
      manner. However, the involvement of the proteasome in other heterochromatin
      regions remained largely unknown. In the present study, we investigated the non
      proteolytic role of the 19S proteasome in subtelomere and facultative
      heterochromatin regions. Using the non-proteolytic mutant, rpt4-1, we show that
      the 19S proteasome is involved in regulating subtelomere silencing and
      facultative heterochromatin formation in fission yeast. In addition to this
      proteasome-related regulation, we also observed a distinct pathway that regulates
      subtelomere silencing and facultative heterochromatin formation through the Paf1
      complex subunit, Leo1. Our comparison of the two pathways revealed a new group of
      heterochromatin domains that are regulated exclusively by the proteasome pathway.
      Taken together, our findings reveal that the proteasome is involved in the global
      regulation of facultative and constitutive heterochromatin.

PMID- 29214405
TI  - Spiritual Well-Being and Its Relationship with Mindfulness, Self-Compassion and
      Satisfaction with Life in Baccalaureate Nursing Students: A Correlation Study.
AB  - The present study aimed to explore the correlates and predictors of spiritual
      well-being among nursing students. One hundred and forty-five BSc nursing
      students were recruited from three nursing colleges in Bangalore, Karnataka,
      India. Data were collected using SHALOM, FMI, SCS-SF and SWLS questionnaires and
      analysed by the Pearson correlation test and multiple regression analysis. The
      results of our study revealed a significant correlation between variables, and a
      considerable amount of variance was explained by self-compassion, mindfulness and
      satisfaction with life on personal, communal, environmental and transcendental
      domains of spiritual well-being.

PMID- 29214406
TI  - Exogenous gene can be expressed by a recombinant Bombyx mori cypovirus.
AB  - Bombyx mori cypovirus (BmCPV) is one of the major viral pathogen for silkworm,
      and the genome of BmCPV is composed of 10 dsRNA segments. As construction system
      of recombinant BmCPV (rBmCPV) is scanty, researchers achieved little progress in
      studying gene function of BmCPV in recent decades. Here, 10 recombinant plasmids
      with a full-length cDNA of viral genome segments S1-S10 containing T7 promoter
      were constructed. After cotransfecting the BmN cells with the mixture of 10 in
      vitro-transcribed RNAs, pathological changes were observed. Real-time PCR and
      Western blot showed viral gene vp1 and structural proteins were expressed. It is
      found the genome of the rBmCPV is composed of 10 dsRNA segments similar to those
      of wild-type BmCPV. Moreover, viral particles and polyhedron with virions can be
      generated in the cotransfected cells and the injected silkworm midguts. These
      findings confirmed the formation of infective rBmCPV. Additionally, we found
      viable rBmCPV was generated by cotransfecting the mixture of in vitro-transcribed
      S1-S9 RNAs into the cultured cells, confirming polh was not essential for BmCPV
      replication. Moreover, an infectious rBmCPV expressing the DsRed protein was
      constructed based on this system. Further investigation showed S2 and S7 segments
      are indispensible for viral proliferation. Our findings demonstrated the
      construction system of rBmCPV can be utilized for exploring viral replication and
      pathogenesis, and investigated method for constructing rBmCPV will certainly
      facilitate developing novel biopesticides and expressing exogenous gene in the
      midgut of silkworm.

PMID- 29214407
TI  - Clinical features and pathogenesis of membranoproliferative glomerulonephritis: a
      nationwide analysis of the Japan renal biopsy registry from 2007 to 2015.
AB  - BACKGROUND: The incidence and age distribution of membranoproliferative
      glomerulonephritis (MPGN) vary throughout the world by race and ethnicity. We
      sought to evaluate the clinical features, pathogenesis, and age distribution of
      MPGN among a large nationwide data from the Japan Renal Biopsy Registry (J-RBR).
      METHODS: A cross-sectional survey of 593 patients with MPGN (types I and III)
      registered in the J-RBR between 2007 and 2015 was conducted. Clinical parameters,
      and laboratory findings at diagnosis were compared between children (< 20 years),
      adults (20-64 years), and elderly patients (>= 65 years). RESULTS: The median age
      of the patients was 59.0 years and mean proteinuria was 3.7 g/day. The rate of
      nephrotic syndrome was significantly higher in adults (40.4%) and elderly
      patients (54.0%) than in children (14.9%), whereas the rate of chronic
      glomerulonephritis was significantly higher in children (66.2%) than in adults
      (34.4%) and elderly patients (31.2%). According to the CGA risk classification,
      high-risk (red zone) cases accounted for 3.4% of children, 52.5% of adults and
      84.1% of elderly patients with MPGN. As for pathogenesis, primary MPGN was most
      frequent (56.0%). Lupus nephritis was the most common disease among adult
      patients with secondary MPGN, whereas infectious disease was more common in
      elderly patients. Multiple regression analysis revealed that high systolic blood
      pressure and high proteinuria were independent factors associated with decreased
      estimated glomerular filtration rate (eGFR) in adults and elderly patients with
      MPGN. CONCLUSIONS: In Japan, adults and elderly patients with MPGN had a lower
      eGFR and severer proteinuria than children.

PMID- 29214408
TI  - Anticipated HIV Stigma and Delays in Regular HIV Testing Behaviors Among Sexually
      Active Young Gay, Bisexual, and Other Men Who Have Sex with Men and Transgender
      Women.
AB  - Young gay, bisexual and other men who have sex with men (YGBMSM) and young
      transgender women are disproportionately affected by HIV/AIDS. The success of
      biomedical prevention strategies is predicated on regular HIV testing; however,
      there has been limited uptake of testing among YGBMSM and young transgender
      women. Anticipated HIV stigma-expecting rejection as a result of seroconversion-
      may serve as a significant barrier to testing. A cross-sectional sample of YGBMSM
      (n = 719, 95.5%) and young transgender women (n = 33, 4.4%) ages 15-24 were
      recruited to participate in a one-time survey. Approximately one-third of youth
      had not tested within the last 6 months. In a multivariable model, anticipated
      HIV stigma and reporting a non-gay identity were associated with an increased
      odds of delaying regular HIV testing. Future research and interventions are
      warranted to address HIV stigma, in order to increase regular HIV testing among
      YGBMSM and transgender women.

PMID- 29214409
TI  - Strategies to Implement Pre-exposure Prophylaxis with Men Who Have Sex with Men
      in Ukraine.
AB  - Ukrainian men who have sex with men (MSM) remain highly stigmatized group with
      HIV prevalence as high as 23%. Despite documented effectiveness of pre-exposure
      prophylaxis (PrEP), PrEP remains unavailable in Ukraine. The aim of this study
      was to elicit MSM preferences in order to inform program development to
      facilitate successful delivery of PrEP to Ukrainian MSM. 1184 MSM were recruited
      through social networking applications to complete a stated preference (choice
      based conjoint) survey. Respondents completed 14 choice tasks presenting
      experimentally-varied combinations of five attributes related to PrEP
      administration (dosing frequency, dispensing venue, prescription practices,
      adherence support, and costs). Latent class analysis was used to estimate the
      relative importance of each attribute and preferences across nine possible PrEP
      delivery programs. Preferences clustered into five groups. PrEP affordability was
      the most influential attribute across groups, followed by dosing strategy. Only
      one group preferred injectable PrEP (n = 216), while the other four groups
      disliked daily PrEP and strongly preferred the 'on demand' option. One group (n =
      258) almost exclusively considered cost in their decision making. One group (n =
      151) had very low level of interest in PrEP initiation correlated with low self
      perceived risk for HIV. The two most at-risk groups (n = 415) were also more
      sensitive to changes in program delivery. PrEP uptake among MSM is most likely to
      be successful when PrEP is affordable, its implementation is targeted, provided
      as "on-demand" with associated education, and when more thorough medical care and
      related testing is provided to at-risk populations. Its introduction will need
      affirmation by the Ukrainian government, and guidelines that reflect safety,
      efficacy, and patient preferences.

PMID- 29214410
TI  - A Cross-Sectional Study of Depressive Symptoms and Risky Alcohol Use Behaviors
      Among HIV Primary Care Patients in New York City.
AB  - An association between problem drinking and depression among HIV-infected
      individuals has been previously demonstrated; however, which specific risky
      drinking behaviors are associated with higher levels of depression has not yet
      been investigated. Using an adult sample of HIV-infected primary care patients
      (78% male, 94% Black or Hispanic), we investigated whether depressive symptoms
      are associated with various risky drinking behaviors. Participants were
      administered the Beck Depression Inventory-II to assess depressive symptoms, and
      the Alcohol Use Disorders and Associated Disabilities Interview Schedule-IV to
      evaluate alcohol involvement. Participants with depressive symptoms (26%) were at
      higher risk for alcohol dependence [adjusted odds ratio (AOR) 3.8; 95% CI 2.0
      7.2], regular binge drinking (AOR 2.0; 95% CI 1.1-3.8), and regular daytime
      drinking (AOR 2.1; 95% CI 1.2-3.8), in comparison with their non-depressed
      counterparts. Because both depression and unhealthy drinking negatively affect
      medication adherence and clinical outcomes, a better understanding of the
      association between depression and certain risky drinking behaviors among HIV
      infected individuals is vital to improving their care and prognoses.

PMID- 29214411
TI  - Correction to: 'Test and Treat' Among Women at High Risk for HIV-Infection in
      Kampala, Uganda: Antiretroviral Therapy Initiation and Associated Factors.
AB  - The original version of this article unfortunately contained an error. The
      incorrect range should be replaced in the in the second sentence of the
      Introduction section. The correct sentence should read as: These key populations
      and their sexual partners account for 10-51% of new infections in sub-Saharan
      Africa (SSA) [6-8]. The original article has been corrected.

PMID- 29214412
TI  - Gestational age at birth and risk of intellectual disability without a common
      genetic cause.
AB  - Preterm birth is linked to intellectual disability and there is evidence to
      suggest post-term birth may also incur risk. However, these associations have not
      yet been investigated in the absence of common genetic causes of intellectual
      disability, where risk associated with late delivery may be preventable. We
      therefore aimed to examine risk of intellectual disability without a common
      genetic cause across the entire range of gestation, using a matched-sibling
      design to account for unmeasured confounding by shared familial factors. We
      conducted a population-based retrospective study using data from the Stockholm
      Youth Cohort (n = 499,621) and examined associations in a nested cohort of
      matched outcome-discordant siblings (n = 8034). Risk of intellectual disability
      was greatest among those born extremely early (adjusted OR24 weeks = 14.54 [95%
      CI 11.46-18.44]), lessening with advancing gestational age toward term (aOR32
      weeks = 3.59 [3.22-4.01]; aOR37weeks = 1.50 [1.38-1.63]); aOR38 weeks = 1.26
      [1.16-1.37]; aOR39 weeks = 1.10 [1.04-1.17]) and increasing with advancing
      gestational age post-term (aOR42 weeks = 1.16 [1.08-1.25]; aOR43 weeks = 1.41
      [1.21-1.64]; aOR44 weeks = 1.71 [1.34-2.18]; aOR45 weeks = 2.07 [1.47-2.92]).
      Associations persisted in a cohort of matched siblings suggesting they were
      robust against confounding by shared familial traits. Risk of intellectual
      disability was greatest among children showing evidence of fetal growth
      restriction, especially when birth occurred before or after term. Birth at non
      optimal gestational duration may be linked causally with greater risk of
      intellectual disability. The mechanisms underlying these associations need to be
      elucidated as they are relevant to clinical practice concerning elective delivery
      around term and mitigation of risk in post-term children.

PMID- 29214413
TI  - New cancer cases in France in 2015 attributable to infectious agents: a
      systematic review and meta-analysis.
AB  - To provide an assessment of the burden of cancer in France in 2015 attributable
      to infectious agents. A systematic literature review in French representative
      cancer cases series was undertaken of the prevalence of infectious agents with
      the major associated cancer types. PubMed was searched for original studies
      published up to September 2016; random-effects meta-analyses were performed.
      Cancer incidence data were obtained from the French Cancer Registries Network,
      thereby allowing the calculation of national incidence estimates. The number of
      new cancer cases attributable to infectious agents was calculated using
      population-attributable fractions according to published methods. Of the 352,000
      new cancer cases in France in 2015, 14,336 (4.1% of all new cancer cases) were
      attributable to infectious agents. The largest contributors were human
      papillomavirus (HPV) and Helicobacter pylori, responsible for 6333 and 4406 new
      cancer cases (1.8 and 1.3% of all new cancer cases) respectively. Infectious
      agents caused a non-negligible number of new cancer cases in France in 2015. Most
      of these cancers were preventable. The expansion of vaccination (i.e., for
      hepatitis B virus and HPV) and screen-and-treat programs (for HPV and hepatitis C
      virus, and possibly for H. pylori) could greatly reduce this cancer burden.

PMID- 29214414
TI  - Understanding the need for assistance with survey completion in people with
      Huntington disease.
AB  - PURPOSE: In Huntington disease (HD), motor, cognitive, and psychiatric changes
      can have a detrimental impact on health-related quality of life (HRQOL). The
      purpose of this paper is to describe the extent and type of assistance needed to
      complete online HRQOL surveys, and the impact of assistance on HRQOL scores.
      METHODS: A patient-reported outcome measurement system was developed for HD
      specific HRQOL. Individuals across the prodromal and diagnosed disease severity
      spectrum (n = 532) completed surveys by computer, and reported the amount and
      type of assistance they received. RESULTS: Some participants (n = 56; 10.5%) did
      not complete all surveys; this group had larger proportions with late stage
      disease, racial/ethnic minority status, low education and single marital status,
      and poorer motor, independence and cognitive function compared to those who
      completed all surveys (n = 476). Overall, 72% of individuals did not receive
      assistance, 11% received computer assistance only, and 17% received assistance
      answering the survey questions. The majority of late stage individuals (78%)
      received some assistance compared to early stage (29%) and prodromal individuals
      (< 1%). Those who received assistance had higher proportions with late stage
      disease, were older, had less education, and had poorer functional and cognitive
      skills. Before and after adjustment for sociodemographic and clinical
      characteristics, those who received assistance had poorer scores on some HRQOL
      outcomes than those who did not receive assistance. CONCLUSIONS: Computer-based
      assessments are feasible for many persons with HD, although other methods may
      also be needed. Clinicians and researchers should develop strategies to assist
      people with HD to complete HRQOL surveys.

PMID- 29214415
TI  - A multi-center pragmatic, randomized, feasibility trial comparing standard of
      care schedules of filgrastim administration for primary febrile neutropenia
      prophylaxis in early-stage breast cancer.
AB  - INTRODUCTION: The most effective duration of filgrastim as primary febrile
      neutropenia (FN) prophylaxis in early breast cancer (EBC) patients is unknown.
      Despite significant differences in cost and toxicity, no prospective trial has
      been performed to optimize practice. We assessed the feasibility of using a novel
      pragmatic trial model to compare the most commonly used schedules of filgrastim.
      METHODS: Early breast cancer patients receiving chemotherapy were randomized to
      5, 7, or 10 days of filgrastim as primary FN prophylaxis. The trial methodology
      integrated broad eligibility criteria, simply defined endpoints, an integrated
      consent model incorporating oral consent, and web-based randomization in the
      clinic. Feasibility was reflected through a combination of primary endpoints
      including patient and physician engagement (if > 50% of appropriate patients
      approached agree to participate, and if > 50% of physicians approached patients
      for the study). Secondary endpoints included the first occurrence rates of FN,
      treatment-related hospital admission, or chemotherapy dose
      reductions/delays/discontinuation. RESULTS: From May 2015 to August 2016, 142/149
      (95.3%) patients approached agreed to participate and were randomized. Seventeen
      of 24 (70.8%) medical oncologists approached and randomized patients. The 142
      patients received a total of 495 cycles of chemotherapy. Aggregate incidences of
      a first event by patient were FN (8/142, 5.6%), treatment-related hospitalization
      (6/142, 4.2%), chemotherapy discontinuation (7/142, 4.9%), chemotherapy delays
      (5/142, 3.5%), and chemotherapy dose reduction (18/142, 12.7%). Overall, 31.7%
      (45/142) of patients and 9.0% (45/495) of chemotherapy cycles were associated
      with one of these first events. CONCLUSION: This study met its feasibility
      endpoints. This novel pragmatic trial approach offers a means of comparing
      standard of care treatments in a practical and cost-effective manner. The trial
      will now be expanded to compare rates of FN between the three filgrastim
      schedules. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02428114.

PMID- 29214416
TI  - Breast-conserving surgery following neoadjuvant therapy-a systematic review on
      surgical outcomes.
AB  - PURPOSE: Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer
      treatment. One of the main goals of NACT is to reduce the extent of local surgery
      of the breast and axilla. The aim of this study was to determine surgical
      outcomes for patients receiving breast-conserving therapy (BCT) after NACT,
      including margin status plus secondary surgeries, excision volumes, and cosmetic
      outcomes. METHODS: A systematic review was performed in accordance with PRISMA
      principles. Pubmed, MEDLINE, Embase, and the Cochrane Library were searched for
      studies investigating the results of BCT following NACT. The main study outcomes
      were margin status, additional local therapies, excision volumes, and cosmetic
      outcomes. Non-comparative studies on NACT were also included. Exclusion criteria
      were studies with less than 25 patients, and studies excluding secondary
      mastectomy patients. FINDINGS: Of the 1219 studies screened, 26 studies were
      deemed eligible for analysis, including data from 5379 patients treated with NACT
      and 10,110 patients treated without NACT. Included studies showed wide ranges of
      tumor-involved margins (2-39.8%), secondary surgeries (0-45.4%), and excision
      volumes (43.2-268 cm3) or specimen weight (26.4-233 g) after NACT. Most studies
      were retrospective, with a high heterogeneity and a high risk of bias. Cosmetic
      outcomes after NACT were reported in two single-center cohort studies. Both
      studies showed acceptable cosmetic outcomes. INTERPRETATION: There is currently
      insufficient evidence to suggest that NACT improves surgical outcomes of BCT. It
      is imperative that clinical trials include patient outcome measures in order to
      allow monitoring and meaningful comparison of treatment outcomes in breast
      cancer.

PMID- 29214417
TI  - Diagnostic and prognostic value of baseline FDG PET/CT skeletal textural features
      in diffuse large B cell lymphoma.
AB  - PURPOSE: Our purpose was to evaluate the diagnostic and prognostic value of
      skeletal textural features (TFs) on baseline FDG PET in diffuse large B cell
      lymphoma (DLBCL) patients. METHODS: Eighty-two patients with DLBCL who underwent
      a bone marrow biopsy (BMB) and a PET scan between December 2008 and December 2015
      were included. Two readers blinded to the BMB results visually assessed PET
      images for bone marrow involvement (BMI) in consensus, and a third observer drew
      a volume of interest (VOI) encompassing the axial skeleton and the pelvis, which
      was used to assess skeletal TFs. ROC analysis was used to determine the best TF
      able to diagnose BMI among four first-order, six second-order and 11 third-order
      metrics, which was then compared for diagnosis and prognosis in disease-free
      patients (BMB-/PET-) versus patients considered to have BMI (BMB+/PET-, BMB
      /PET+, and BMB+/PET+). RESULTS: Twenty-two out of 82 patients (26.8%) had BMI: 13
      BMB-/PET+, eight BMB+/PET+ and one BMB+/PET-. Among the nine BMB+ patients, one
      had discordant BMI identified by both visual and TF PET assessment. ROC analysis
      showed that SkewnessH, a first-order metric, was the best parameter for
      identifying BMI with sensitivity and specificity of 81.8% and 81.7%,
      respectively. SkewnessH demonstrated better discriminative power over BMB and PET
      visual analysis for patient stratification: hazard ratios (HR), 3.78 (P = 0.02)
      versus 2.81 (P = 0.06) for overall survival (OS) and HR, 3.17 (P = 0.03) versus
      1.26 (P = 0.70) for progression-free survival (PFS). In multivariate analysis
      accounting for IPI score, bulky status, haemoglobin and SkewnessH, the only
      independent predictor of OS was the IPI score, while the only independent
      predictor of PFS was SkewnessH. CONCLUSION: The better discriminative power of
      skeletal heterogeneity for risk stratification compared to BMB and PET visual
      analysis in the overall population, and more specifically in BMB-/PET- patients,
      suggests that it can be useful to identify diagnostically overlooked BMI.

PMID- 29214418
TI  - Choice of desflurane or propofol for the maintenance of general anesthesia does
      not affect the risk of periprocedural myocardial damage in patients undergoing
      transfemoral transcatheter aortic valve implantation.
AB  - PURPOSE: This study aimed to reveal whether the occurrence of periprocedural
      myocardial damage (PMD) decreases in patients who received volatile anesthetics
      to maintain general anesthesia compared with those who received propofol during
      transcatheter aortic valve implantation (TAVI). METHODS: We included one hundred
      and forty adult patients who underwent transfemoral TAVI under general anesthesia
      from January 2015 to March 2017 in this single-center retrospective review. We
      compared the rate of patients who developed PMD between those who received
      desflurane (Group D, n = 72) and propofol (Group P, n = 68) for anesthetic
      maintenance. PMD was represented by the peak levels of creatine kinase myocardial
      band (CK-MB) and troponin I within 72 h following the procedure and defined as an
      increase >5 times in CK-MB or >15 times in troponin I compared with the
      institutional upper reference limits. Further analysis was performed to identify
      the independent predictors of PMD. RESULTS: There was no significant difference
      in the rate of PMD between groups (Group D 72.2% to Group P 70.6%, P = 0.85) or
      levels of CK-MB (Group D 7.85 [1.3-72.7] ng/mL to Group P 8.45 [1.8-49.7] ng/mL;
      P = 0.59) and troponin I (Group D 1.061 [0.050-10.8] ng/mL to Group P 1.214
      [0.036-29.0] ng/mL; P = 0.97). The risk of PMD was higher in patients with more
      intraprocedural blood loss (odds ratio 1.49 per 100 mL, P = 0.048) and lower in
      those with an implanted permanent pacemaker (odds ratio 0.17; P = 0.02).
      CONCLUSIONS: Desflurane does not appear to be more cardioprotective than propofol
      when used for anesthetic maintenance in patients undergoing transfemoral TAVI.

PMID- 29214419
TI  - Parabolic flight: experiencing zero gravity to envisage the future of human
      evolution.

PMID- 29214420
TI  - Aerobic reactions of antitumor active dirhodium(II) tetraacetate Rh2(CH3COO)4
      with glutathione.
AB  - The aerobic reaction between glutathione (H3A) and dirhodium(II) tetraacetate,
      Rh2(AcO)4 (AcO- = CH3COO-), in aqueous solution (pH 7.4) breaks up the direct
      RhII-RhII bond and its carboxylate framework, as evidenced by UV-Vis
      spectroscopy. After purifying the reaction product using size exclusion
      chromatography, electrospray ionization mass spectrometry (ESI-MS) of the
      solution showed binuclear [Formula: see text] and [Formula: see text] ions.
      Evaporation yielded a solid compound, [Formula: see text], for which Rh K-edge
      extended X-ray absorption fine structure (EXAFS) spectroscopy revealed ~ 2 Rh-O
      (2.08 +/- 0.02 A) and ~ 4 Rh-S (2.33 +/- 0.02 A) bond distances around each RhIII
      center, and the RhIII..RhIII distance 3.11 +/- 0.02 A, close to that in
      dirhodium(III) complexes with three bridging thiolates connecting [Formula: see
      text] units. The 13C CPMAS NMR spectrum of the RhIII-glutathione complex showed a
      change ?delta C > 6 ppm in the chemical shift of the COO- signal, indicating some
      carboxylate coordination to the Rh(III) ions. This study shows that under aerobic
      conditions glutathione enables oxidation of Rh2(AcO)4 and thus reduces its
      antitumor efficiency. The reaction of Rh2(AcO)4 with glutathione was investigated
      by ESI-MS, UV-Vis, 13C NMR and X-ray absorption spectroscopy, revealing that
      glutathione breaks down the carboxylate framework enabling oxidization of the
      [Formula: see text] core to Rh(III) dimeric units, bridged by three thiolates.

PMID- 29214421
TI  - Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid
      Computational/Physiological Study.
AB  - Atrial fibrillation is the most common rhythm disorder of the heart associated
      with a rapid and irregular beating of the upper chambers. Activation mapping
      remains the gold standard to diagnose and interpret atrial fibrillation. However,
      fibrillatory activation maps are highly sensitive to far-field effects, and often
      disagree with other optical mapping modalities. Here we show that computational
      modeling can identify spurious non-local components of atrial fibrillation
      electrograms and improve activation mapping. We motivate our approach with a
      cohort of patients with potential drivers of persistent atrial fibrillation. In a
      computational study using a monodomain Maleckar model, we demonstrate that in
      organized rhythms, electrograms successfully track local activation, whereas in
      atrial fibrillation, electrograms are sensitive to spiral wave distance and
      number, spiral tip trajectories, and effects of fibrosis. In a clinical study, we
      analyzed n = 15 patients with persistent atrial fibrillation that was terminated
      by limited ablation. In five cases, traditional activation maps revealed a spiral
      wave at sites of termination; in ten cases, electrogram timings were ambiguous
      and activation maps showed incomplete reentry. By adjusting electrogram timing
      through computational modeling, we found rotational activation, which was
      undetectable with conventional methods. Our results demonstrate that
      computational modeling can identify non-local deflections to improve activation
      mapping and explain how and where ablation can terminate persistent atrial
      fibrillation. Our hybrid computational/physiological approach has the potential
      to optimize map-guided ablation and improve ablation therapy in atrial
      fibrillation.

PMID- 29214422
TI  - Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis
      Associated Colorectal Cancer.
AB  - BACKGROUND/AIMS: Ulcerative colitis is a remitting and relapsing inflammatory
      bowel disorder. Current treatments are limited, and if poorly controlled, colitis
      may progress to colorectal cancer. Previously, Emu Oil protected the intestine in
      experimental models of gut damage. We aimed to determine whether Emu Oil could
      reduce the severity of chronic colitis and prevent the onset of neoplasia in a
      mouse model of colitis-associated colorectal cancer. METHODS: Female C57BL/6 mice
      were injected (day 0) with azoxymethane, followed by ad libitum access to three
      dextran sulfate sodium/water cycles (7 days of dextran sulfate sodium and 14 days
      of water). Mice (n = 9/group) were orally administered either water or Emu Oil
      (low dose 80 uL or high dose 160 uL), thrice weekly for 9 weeks. Bodyweight and
      disease activity index were measured daily. Colitis progression was monitored by
      colonoscopy on days 20, 41 and 62. At killing, tumor number and size were
      recorded. RESULTS: Azoxymethane/dextran sulfate sodium induced significant
      bodyweight loss (maximum 24%) which was attenuated by Emu Oil treatment (low dose
      days 9, 10, 14: maximum 7%; high dose days 7-15, 30-36: maximum 11%; p < 0.05).
      Emu Oil reduced disease activity index of azoxymethane/dextran sulfate sodium
      mice at most time points (maximum 20%; p < 0.05). Additionally, Emu Oil reduced
      colonoscopically assessed colitis severity (days 20 and 62) compared to disease
      controls (p < 0.05). Finally, in azoxymethane/dextran sulfate sodium mice, low
      dose Emu Oil resulted in fewer small colonic tumors (p < 0.05) compared to
      controls. CONCLUSIONS: Emu Oil improved clinical indicators and reduced severity
      of colitis-associated colorectal cancer, suggesting therapeutic potential in
      colitis management.

PMID- 29214423
TI  - Comparative Analysis of Gene Expression Profiles Involved in Calcium Signaling
      Pathways Using the NLVH Animal Model of Schizophrenia.
AB  - In this study, we evaluated the expression profile changes of genes that
      intervene in the calcium signaling pathway, in young and adult Wistar rats, using
      the animal model of neonatal lesion in ventral hippocampus (NLVH) (a recognized
      animal model for schizophrenia) and compared to the group of control animals
      (Sham). Through microarray technology, gene expression profiles were obtained
      from the three brain areas (nucleus accumbens, prefrontal cortex, and
      hippocampus) of young male Wistar rats (45 days) and adults (90 days) whether or
      not subjected to NLVH. The calcium signaling pathway reported a greater number of
      differentially expressed genes with z-score two values, > 2 (over-expression) and
      < - 2 (under-expression), in the three evaluated areas. The comparative analyses
      of this approach were performed in juvenile and adult rats with ventral
      hippocampal lesion in neonate rats (NLVH). NLVH influenced change expressions in
      various genes involved in Ca2+ homeostasis, including Cacna1d, Atp2a2, Adcy2,
      Ppp3cb, and Ptk2b. The expression of Adcy2, Ppp3cb, and Ptk2b genes changed in
      both age groups; therefore, the study of gene expression profiles between
      juvenile and adult rats may help to understand the molecular mechanisms of
      schizophrenia.

PMID- 29214425
TI  - Can smartphones be used to bring computer-based tasks from the lab to the field?
      A mobile experience-sampling method study about the pace of life.
AB  - Researchers are increasingly using smartphones to collect scientific data. To
      date, most smartphone studies have collected questionnaire data or data from the
      built-in sensors. So far, few studies have analyzed whether smartphones can also
      be used to conduct computer-based tasks (CBTs). Using a mobile experience
      sampling method study and a computer-based tapping task as examples (N = 246;
      twice a day for three weeks, 6,000+ measurements), we analyzed how well
      smartphones can be used to conduct a CBT. We assessed methodological aspects such
      as potential technologically induced problems, dropout, task noncompliance, and
      the accuracy of millisecond measurements. Overall, we found few problems: Dropout
      rate was low, and the time measurements were very accurate. Nevertheless,
      particularly at the beginning of the study, some participants did not comply with
      the task instructions, probably because they did not read the instructions before
      beginning the task. To summarize, the results suggest that smartphones can be
      used to transfer CBTs from the lab to the field, and that real-world variations
      across device manufacturers, OS types, and CPU load conditions did not
      substantially distort the results.

PMID- 29214426
TI  - A single-level random-effects cross-lagged panel model for longitudinal mediation
      analysis.
AB  - Cross-lagged panel models (CLPMs) are widely used to test mediation with
      longitudinal panel data. One major limitation of the CLPMs is that the model
      effects are assumed to be fixed across individuals. This assumption is likely to
      be violated (i.e., the model effects are random across individuals) in practice.
      When this happens, the CLPMs can potentially yield biased parameter estimates and
      misleading statistical inferences. This article proposes a model named a random
      effects cross-lagged panel model (RE-CLPM) to account for random effects in
      CLPMs. Simulation studies show that the RE-CLPM outperforms the CLPM in
      recovering the mean indirect and direct effects in a longitudinal mediation
      analysis when random effects exist in the population. The performance of the RE
      CLPM is robust to a certain degree, even when the random effects are not normally
      distributed. In addition, the RE-CLPM does not produce harmful results when the
      model effects are in fact fixed in the population. Implications of the simulation
      studies and potential directions for future research are discussed.

PMID- 29214424
TI  - iTRAQ-based comparative proteomic analysis provides insights into somatic
      embryogenesis in Gossypium hirsutum L.
AB  - KEY MESSAGE: iTRAQ based proteomic identified key proteins and provided new
      insights into the molecular mechanisms underlying somatic embryogenesis in
      cotton. Somatic embryogenesis, which involves cell dedifferentiation and
      redifferentiation, has been used as a model system for understanding molecular
      events of plant embryo development in vitro. In this study, we performed
      comparative proteomics analysis using samples of non-embryogenic callus (NEC),
      embryogenic callus (EC) and somatic embryo (SE) using the isobaric tags for
      relative and absolute quantitation (iTRAQ) technology. In total, 5892 proteins
      were identified amongst the three samples. The majority of these proteins (93.4%)
      were found to have catalytic activity, binding activity, transporter activity or
      structural molecular activity. Of these proteins, 1024 and 858 were
      differentially expressed in NEC versus EC and EC versus SE, respectively.
      Compared to NEC, EC had 452 and 572 down- and up-regulated proteins,
      respectively, and compared to EC, SE had 647 and 221 down- and up-regulated
      proteins, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis
      indicated that genetic information transmission, plant hormone transduction,
      glycolysis, fatty acid biosynthesis and metabolism, galactose metabolism were the
      top pathways involved in somatic embryogenesis. Our proteomics results not only
      confirmed our previous transcriptomic results on the role of the polyamine
      metabolic pathways and stress responses in cotton somatic embryogenesis, but
      identified key proteins important for cotton somatic embryogenesis and provided
      new insights into the molecular mechanisms underlying somatic embryogenesis in
      cotton.

PMID- 29214428
TI  - An Invitation to Pharmacostatics.
AB  - Pharmacology, the study of interactions between biological processes and
      therapeutic agents, is traditionally presented as consisting of two
      subdisciplines: pharmacokinetics, which is about the distribution and metabolism
      of drugs in organisms, and pharmacodynamics, which is about the organisms'
      response to drugs. In discovery-stage pharmacology however, one primary concern
      is what we call pharmacostatics, the characterization of equilibrium parameters
      and states of core interactions of physiologic and therapeutic interest. This
      usually takes the form of studying dose-response curves, without consideration
      for the relevant qualitative properties of the underlying reaction networks,
      e.g., the existence, multiplicity and asymptotic stability of steady states.
      Furthermore, steady-state calculations customarily employ manually derived closed
      form expressions based on approximating assumptions. While these formulas may
      seem adequate most of the time, the assumptions need not apply, and there are
      genuine though seemingly uncommon cases where this approach is not feasible
      and/or fails to explain non-monotone dose-response curves. It is this paper's aim
      to stimulate interest in mathematical problems arising in pharmacostatics. We
      specifically pose two problems about a particular relevant class of networks of
      reversible binding reactions. The first problem is to exploit a certain fixed
      point formulation of the equilibrium equation to devise an algorithmic method
      that would be compellingly preferable to current practice in the pharmacostatics
      context. The second problem is to explicitly anticipate the possibility of non
      monotone dose-response curves from network topology. Addressing these problems
      would positively impact biopharmaceutical research, and they have inherent
      mathematical interest.

PMID- 29214427
TI  - Characterization of PD-L1 expression in Chinese non-small cell lung cancer
      patients with PTEN expression as a means for tissue quality screening.
AB  - The goal of this study is to evaluate PD-L1 prevalence and its association with
      major clinical characteristics in Chinese non-small cell lung cancer (NSCLC)
      patients to inform the clinical development of anti-PD1/PD-L1 agents in this
      population. We used phosphatase and tensin homolog (PTEN) expression through IHC
      as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue
      microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were
      then analyzed with a clinically validated PD-L1 IHC assay. The results were
      correlated with baseline characteristics and clinical outcomes. PTEN IHC showed
      that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With
      a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1
      level was much lower in EGFR-mutant patients and seemed to be a favorable
      prognostic factor for both overall survival (OS) and recurrence-free survival
      (RFS). These findings were confirmed in the whole-section samples except that
      their survival data were not mature enough for correlation analysis. In summary,
      PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese
      NSCLC samples, negatively correlated with EGFR mutation and seemed to be a
      favorable prognostic factor for both OS and RFS. Notably, the different results
      from PTEN-qualified and PTEN-disqualified samples underscore the importance of
      tissue quality control prior to biomarker testing.

PMID- 29214429
TI  - Reduction and Stability Analysis of a Transcription-Translation Model of RNA
      Polymerase.
AB  - The aim of this paper is to analyze the dynamical behavior of biological models
      of gene transcription and translation. We focus on a particular positive feedback
      loop governing the synthesis of RNA polymerase, needed for transcribing its own
      gene. We write a high-dimension model based on mass action laws and reduce it to
      a two-variable model (RNA polymerase and its mRNA) by means of monotone system
      theory and timescale arguments. We show that the reduced model has either a
      single globally stable trivial equilibrium in (0, 0), or an unstable zero
      equilibrium and a globally stable positive one. We give generalizations of this
      model, notably with a variable growth rate. The dynamical behavior of this system
      can be related to biological observations on the bacterium Escherichia coli.

PMID- 29214430
TI  - Functional Cause of Dysphagia Improved with Cognitive Behavioural Treatment.

PMID- 29214432
TI  - John Melissas, MD, PhD, FACS.

PMID- 29214431
TI  - Establishment and characterization of a kidney cell line from kelp grouper
      Epinephelus moara.
AB  - A novel cell line, Epinephelus moara kidney cell line (EMK), was established from
      kidneys of kelp grouper E. moara. Cells were cultured at 24  degrees C in
      Leibovitz's L-15 medium (L15) supplemented with antibiotics, basic fibroblast
      growth factor (bFGF), foetal bovine serum (FBS) and 2-mercaptoethanol (2-ME). EMK
      cells, fibroblastic in morphology, proliferated to 100% confluency in 3-4 days
      and were subcultured for over 50 passages. The cells could grow from 18 to 30 
      degrees C, with optimal growth at 24  degrees C. Chromosome analysis indicated
      that the modal chromosome number was 48 in the cells at passage 42. Green
      fluorescent signals could be observed in EMK cells when the cells were
      transfected with pEGFP-N3 plasmid. Moreover, a significant cytopathic effect
      (CPE) was observed in the cells after infection with Singapore grouper iridovirus
      (SGIV) or nervous necrosis virus (NNV), and viral replication was confirmed by
      quantitative real-time PCR (qPCR). These results suggested the potential of the
      EMK cell line for studies of transgene and pathogenesis of SGIV and NNV.

PMID- 29214433
TI  - Overexpression of osteopontin promotes cell proliferation and migration in human
      nasopharyngeal carcinoma and is associated with poor prognosis.
AB  - Nasopharyngeal carcinoma (NPC), a malignant tumor at the top and side of the
      nasopharyngeal cavity, highly occurs in the southern region of China. Cancer cell
      metastasis is one of the leading causes of death in NPC patients. Osteopontin
      (OPN), is a phosphorylated extracellular matrix protein with a variety of
      functions, was found to be overexpressed in many cancers. However, the expression
      and role of OPN in patients with NPC in Guangxi, China are unclear. Here, we
      observed that NPC patients had upregulated OPN at mRNA protein and levels.
      Immunochemistry (IHC) analysis of OPN expression in 68 NPC clinical specimens
      indicated that high expression of OPN had positive correlation with NPC lymph
      node metastasis (P = 0.012), distant metastasis (P = 0.001) and TNM staging (P =
      0.018). Moreover, compared with relatively low OPN, NPC patients with higher
      expression of OPN showed a poorer overall survival rate (P = 0.001, log rank
      test). Multivariate analysis showed that OPN expression in NPC was an independent
      prognostic marker. The proliferation, apoptosis and migration ability of CEN-2Z
      cancer cells in NPC were determined by MTT, flow cytometry and wound-healing
      assays, respectively. Upregulation of OPN in CEN-2Z cancer cells promoted cancer
      cell proliferation and migration, and suppressed apoptosis. In sum, our result
      suggests OPN could be used as a valuable oncoprotein and show that overexpression
      of OPN in NPC may serve as a potential prognostic marker.

PMID- 29214434
TI  - Risk factors for intraoperative bradycardia during ear, nose, throat and
      maxillofacial surgery.
AB  - Intraoperative bradycardia (IOB) is one of the most common cardiac arrhythmias
      observed in clinical anaesthetic practice. Controlled hypotension, as a strategy
      of lowering patient's blood pressure during anesthesia has been practiced for
      decades in head and neck surgery. The aim of our study was to determine the
      incidence and the risk factors for intraoperative bradycardia in maxillofacial,
      ear, nose and throat surgery, as well as to determine whether controlled
      hypotension affects the occurrence of IOB. The retrospective study included 2304
      patients who underwent maxillofacial, ear, nose or throat surgery. We studied the
      influence of: sex, age, comorbidity, type of surgery, duration of anesthesia and
      controlled hypotension on the occurrence of IOB. IOB was registered in 473
      patients (20.5%). Patients with controlled hypotension had IOB significantly more
      often than patients without controlled hypotension (33.9 vs 15.1%) (p = 0.000).
      The significant predictors of IOB were: age (OR = 1.158; 95% CI = 1.068-1.256; p
      = 0.000), sex (OR = 0.786; 95% CI = 0.623-0.993; p = 0.043), ischemic heart
      disease (OR = 2.016; 95% CI = 1.182-3.441; p = 0.010); ear surgery (OR = 1.593;
      95% CI = 1.232-2.060; p = 0.000), anesthesia duration, (OR = 1.006; 95% CI =
      1.004-1.007; p = 0.000) and controlled hypotension (OR = 2.204; 95% CI = 1.761
      2.758; p = 0.000). IOB is common in maxillofacial, ear, nose and throat surgery,
      particularly in male, older age and patients with ishemic heart disease. The ear
      surgery, longer anesthesia duration and controlled hypotension raise the risk for
      occurrence of IOB.

PMID- 29214435
TI  - Exploring Lifetime Accumulation of Criminal Justice Involvement and Associated
      Health and Social Outcomes in a Community-Based Sample of Women who Use Drugs.
AB  - Among people who use illegal drugs, engagement with the criminal justice (CJ)
      system often involves an ongoing, intermittent series of arrests, incarcerations,
      and periods of community supervision. The potential associations between the
      lifetime accumulation of CJ involvement and social and health outcomes is largely
      unexplored. In a cross-sectional sample of women who use crack, heroin, and/ or
      methamphetamine recruited from communities in Oakland, CA (N = 624), we developed
      an approach to characterize CJ accumulation. We used latent class analysis (LCA),
      a multivariate person-centered method that assumes an unobserved categorical
      variable that divides a population into a small number of mutually exclusive and
      exhaustive classes. Using observed measures of incarceration and community
      supervision as indicator variables, we developed a model of CJ accumulation that
      elucidates patterns of involvement as lived by the women in the sample. Based on
      model fit statistics, we selected a three-class model and labeled the classes
      "low," "medium," and "high." We then explored associations between the classes of
      CJ accumulation and health and health-related outcomes using logistic regression.
      The odds of homelessness (p for trend = 0.004), transience (p for trend = 0.017),
      and recent victimization (p for trend = 0.023) were higher among women in higher
      accumulation classes. Higher class of CJ accumulation was associated with higher
      odds of reporting unmet need for physical health care (p for trend < 0.001) and
      mental health care (p for trend = 0.002). The odds of physical health conditions,
      such as hepatitis C infection (p for trend < 0.001) and mental health conditions,
      such as depression (p for trend = 0.003), also increased with higher class of
      accumulation. While the findings described here are limited by the cross
      sectional nature of the study, they suggest that CJ accumulation is a potentially
      meaningful concept for assessing associations between the CJ system and health
      related issues.

PMID- 29214436
TI  - Aggregate Trends of Hepatitis C Virus Identification and Treatment in Maryland
      Corrections Fiscal Years 2012-2016.

PMID- 29214437
TI  - Older adults' neural activation in the reward circuit is sensitive to face
      trustworthiness.
AB  - We examined older adult (OA) and younger adult (YA) neural sensitivity to face
      trustworthiness in reward circuit regions, previously found to respond to
      trustworthiness in YA. Interactions of face trustworthiness with age revealed
      effects exclusive to OA in the amygdala and caudate, and an effect that was not
      moderated by age in the dorsal anterior cingulate cortex (dACC). OA, but not YA,
      showed a nonlinear amygdala response to face trustworthiness, with significantly
      stronger activation response to high than to medium trustworthy faces, and no
      difference between low and medium or high. This may explain why an earlier study
      investigating OA amygdala activation to trustworthiness failed to find a
      significant effect, since only the linear low versus high trustworthiness
      difference was assessed. OA, but not YA, also showed significantly stronger
      activation to high than to low trustworthy faces in the right caudate, indicating
      a positive linear effect, consistent with previous YA research, as well as
      significantly stronger activation to high than to medium but not low trustworthy
      faces in the left caudate, indicating a nonlinear effect. Activation in dACC
      across both age groups showed a positive linear effect consistent with previous
      YA research. Finally, OA rated the faces as more trustworthy than did YA across
      all levels of trustworthiness. Future research should examine whether the null
      effects for YA were due to our inclusion of older faces. Research also should
      investigate possible implications of our findings for more ecologically valid OA
      responses to people who vary in facial trustworthiness.

PMID- 29214438
TI  - Interactions between top-down and bottom-up attention in barn owls (Tyto alba).
AB  - Selective attention, the prioritization of behaviorally relevant stimuli for
      behavioral control, is commonly divided into two processes: bottom-up, stimulus
      driven selection and top-down, task-driven selection. Here, we tested two barn
      owls in a visual search task that examines attentional capture of the top-down
      task by bottom-up mechanisms. We trained barn owls to search for a vertical Gabor
      patch embedded in a circular array of differently oriented Gabor distractors (top
      down guided search). To track the point of gaze, a lightweight wireless video
      camera was mounted on the owl's head. Three experiments were conducted in which
      the owls were tested in the following conditions: (1) five distractors; (2) nine
      distractors; (3) five distractors with one distractor surrounded by a red circle;
      or (4) five distractors with a brief sound at the initiation of the stimulus.
      Search times and number of head saccades to reach the target were measured and
      compared between the different conditions. It was found that search time and
      number of saccades to the target increased when the number of distractors was
      larger (condition 2) and when an additional irrelevant salient stimulus, auditory
      or visual, was added to the scene (conditions 3 and 4). These results demonstrate
      that in barn owls, bottom-up attention interacts with top-down attention to shape
      behavior in ways similar to human attentional capture. The findings suggest
      similar attentional principles in taxa that have been evolutionarily separated
      for 300 million years.

PMID- 29214439
TI  - A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in
      Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia
      A.
AB  - BACKGROUND: Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor
      function of activated coagulation factor VIII. In phase I-I/II studies,
      emicizumab reduced the bleeding frequency in patients with severe hemophilia A,
      regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous
      doses of 0.3, 1, and 3 mg/kg. METHODS: Using the phase I-I/II study data,
      population pharmacokinetic and repeated time-to-event (RTTE) modeling were
      performed to quantitatively characterize the relationship between the
      pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations
      were then performed to identify the minimal exposure expected to achieve zero
      bleeding events for 1 year in at least 50% of patients and to select the dosing
      regimens to be tested in phase III studies. RESULTS: The RTTE model adequately
      predicted the bleeding onset over time as a function of plasma emicizumab
      concentration. Simulations suggested that plasma emicizumab concentrations of >= 
      45 MUg/mL should result in zero bleeding events for 1 year in at least 50% of
      patients. This efficacious exposure provided the basis for selecting previously
      untested dosing regimens of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6
      mg/kg every 4 weeks for phase III studies. CONCLUSIONS: A pharmacometric approach
      guided the phase III dose selection of emicizumab in hemophilia A, without
      conducting a conventional dose-finding study. Phase III studies with the selected
      dosing regimens are currently ongoing. This case study indicates that a
      pharmacometric approach can substitute for a conventional dose-finding study in
      rare diseases and will streamline the drug development process.

PMID- 29214440
TI  - MassARRAY-based simultaneous detection of hotspot somatic mutations and recurrent
      fusion genes in papillary thyroid carcinoma: the PTC-MA assay.
AB  - PURPOSE: We exploited the MassARRAY (MA) genotyping platform to develop the "PTC
      MA assay", which allows the simultaneous detection of 13 hotspot mutations, in
      the BRAF, KRAS, NRAS, HRAS, TERT, AKT1, PIK3CA, and EIF1AX genes, and six
      recurrent genetic rearrangements, involving the RET and TRK genes in papillary
      thyroid cancer (PTC). METHODS: The assay was developed using DNA and cDNA from 12
      frozen and 11 formalin-fixed paraffin embedded samples from 23 PTC cases,
      together with positive and negative controls. RESULTS: The PTC-MA assay displays
      high sensitivity towards point mutations and gene rearrangements, detecting their
      presence at frequencies as low as 5%. Moreover, this technique allows
      quantification of the mutated alleles identified at each tested locus.
      CONCLUSIONS: The PTC-MA assay is a novel MA test, which is able to detect fusion
      genes generated by genomic rearrangements concomitantly with the analysis of
      hotspot point mutations, thus allowing the evaluation of key diagnostic,
      prognostic, and therapeutic markers of PTC in a single experiment without any
      informatics analysis. As the assay is sensitive, robust, easily achievable, and
      affordable, it is suitable for the diagnostic practice. Finally, the PTC-MA assay
      can be easily implemented and updated by adding novel genetic markers, according
      to clinical requirements.

PMID- 29214441
TI  - Use of 111In-pentetreotide scintigraphy for diagnosis and management of resistant
      macroprolactinoma.

PMID- 29214442
TI  - Shiga toxin triggers endothelial and podocyte injury: the role of complement
      activation.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) is the offending agent in
      post-diarrhea-associated hemolytic uremic syndrome (HUS), a disorder
      characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute
      kidney failure, with thrombi occluding the renal microvasculature. Endothelial
      dysfunction has been recognized as the trigger event in the development of
      microangiopathic processes. Glomerular endothelial cells are susceptible to the
      toxic effects of Stxs that, via nuclear factor kappa B (NF-kappaB) activation,
      induce the expression of genes encoding for adhesion molecules and chemokines,
      culminating in leukocyte adhesion and platelet thrombus formation on the
      activated endothelium. Complement activation via the alternative pathway has been
      seen in patients during the acute phase of STEC-associated HUS. Experimental
      evidence has highlighted the role of complement proteins in driving glomerular
      endothelium toward a thrombogenic phenotype. At the glomerular level, podocytes
      are also an important target of Stx-induced complement activation. Glomerular
      injury as a consequence of podocyte dysfunction and loss is thus a mechanism that
      might affect long-term renal outcomes in the disease. New approaches to targeting
      the complement system may be useful therapeutic options for patients with STEC
      HUS.

PMID- 29214443
TI  - Contribution of symmetric dimethylarginine to GFR decline in pediatric chronic
      kidney disease.
AB  - BACKGROUND: In pediatric chronic kidney disease (pCKD), traditional factors
      (proteinuria, etiology, and race) do not fully explain disease progression. The
      levels of methylated arginine derivatives (MADs: asymmetric and symmetric
      dimethylarginine, respectively) rise in CKD and increase with CKD progression.
      The impact of MADs on glomerular filtration rate (GFR) decline has not been
      examined in pCKD. The aim of this study was to examine the additive impact of
      baseline (BL) levels of MADs on directly measured GFR (mGFR) decline per year
      (ml/min/1.73 m2/year) for a period of up to 4 years. METHODS: Plasma and data,
      including mGFR by plasma iohexol clearance, were provided by the prospective,
      observational Chronic Kidney Disease in Children study. BL MADs were analyzed by
      high-performance liquid chromatography-tandem mass spectrometry. RESULTS: For 352
      pCKD subjects, the median [interquartile range] BL mGFR was 45 [35, 57]
      ml/min/1.73 m2. The levels of BL MADs were inversely related to the initial mGFR
      and its decline over time (p < 0.0005) but not to the rate of decline.
      Covariates, non-glomerulopathy and Tanner stage of >= 3 demonstrated weaker
      relationships between BL levels and beginning mGFR (p = 0.004 and p = 0.002,
      respectively). CONCLUSIONS: In pCKD, higher concentrations of BL MADs were
      inversely related to BL mGFR. MADs did not affect the CKD progression rate.
      Quantification of this relationship is novel to the pCKD literature.

PMID- 29214444
TI  - The Respiratory Rate: A Neglected Triage Tool for Pre-hospital Identification of
      Trauma Patients.
AB  - BACKGROUND: Under-triaged trauma patients have worse clinical outcomes. We
      evaluated the capability of four pre-hospital variables to identify this
      population at the lowest level trauma activation (level 3). METHODS: A
      retrospective review of adult trauma activations from 2004 to 2014 was completed.
      Pre-hospital vital signs and Glasgow Coma Scale were converted to categorical
      variables. Patients were under-triaged based on meeting current level 1 or 2
      criteria, or requiring a pre-defined critical intervention. Logistic regression
      was used to determine the association between the pre-hospital variables and
      under-triaged patients. Odds ratios and 95% confidence intervals were calculated
      for a comprehensive model, grouping all causes of under-triage as a single unit,
      and 16 individual models, one for each under-triage criterion. A new level 2
      criterion was generated and internally validated. RESULTS: In total, 12,332
      activations occurred during the study period. Four hundred and sixty-six (5.9%)
      patients were under-triaged. Compared to patients with a normal respiratory rate
      (RR), tachypneic patients were more likely to be under-triaged for any reason, OR
      1.7 [1.3-2.1], p < 0.001. In the individual event analysis, tachypneic patients
      were more likely to have flail chest, OR 22 [2.9-168.3], p = 0.003; require a
      chest tube, OR 3 [1.8-4.9], p < 0.001; or require emergent intubation, OR 1.6
      [1.1-2.8], p = 0.04, compared to patients with a normal RR. The data-driven
      triage modification was tachypnea with suspected thoracic injury which reduced
      the under-triage rate by 1.2%. CONCLUSION: Tachypnea with suspected thoracic
      injury is the strongest level 2 triage modification to reduce level 3 under
      triage.

PMID- 29214445
TI  - Auxin enhances grafting success in Carya cathayensis (Chinese hickory).
AB  - MAIN CONCLUSION: Application of auxin to root stock and scion increases the
      success rate of grafting in Chinese hickory. The nuts of the Chinese hickory
      (Carya cathayensis) tree are considered both delicious and healthy. The
      popularity and high demand result is that the hickory nuts are of very high
      economical value for horticulture. This is particularly true for the Zhejiang
      province in eastern China where this tree is widely cultivated. However, there
      are several difficulties surrounding the hickory cultivation, such as for example
      long vegetative growth, tall trees, labour-intensive nut picking, and slow
      variety improvements. These complications form a great bottleneck in the
      expansion of the hickory industry. The development of an efficient grafting
      procedure could surpass at least some of these problems. In this study, we
      demonstrate that application of the auxin indole-3-acetic acid promotes the
      grafting process in hickory, whereas application of the auxin transport inhibitor
      1-N-naphthylphthalamic acid inhibits the grafting process. Furthermore, we have
      identified hickory genes in the PIN, ABCB, and AUX/LAX-families known to encode
      influx and efflux carriers in the polar transport of auxin. We show that
      increased expression of several of these genes, such as CcPIN1b and CcLAX3, is
      correlating with successful grafting.

PMID- 29214447
TI  - Association between common bile duct diameter and abdominal aorta calcium score.
AB  - BACKGROUND AND OBJECTIVE: There is evidence of association between aging and
      increase in the normal upper limit of the common bile duct (CBD) diameter. As
      aging is a documented risk factor for atherosclerosis, and the possible effect
      that atherosclerosis can have on the CBD diameter via affecting its smooth muscle
      contractility and blood flow, we decided to determine the association between CBD
      diameter and atherosclerosis in the abdominal aorta (AA). METHODS: A total of 99
      asymptomatic patients (53 males and 46 females; age range of 18-88 years) without
      history of cholecystectomy who underwent abdominal contrast-enhanced CT scan were
      included. The CBD diameter was measured. The atherosclerosis of AA was quantified
      by Agatston score. RESULTS: Mean (+/- SD) CBD diameter was 6.14 (+/- 1.95) mm;
      range = 2.4-12.7 mm. Agatston score was 0 in 59 patients. In the remaining 40
      patients, median (interquartile range, IQR) Agatston score was 497.5 (2026.3).
      Mean (+/- SD) CBD diameter in patients with Agatston score > 0 was 7.39 (+/-
      2.07) mm compared to 5.29 (+/- 1.32) mm in patients without calcification plaque
      (P < 0.001). A moderate correlation was seen between CBD diameter and Agatston
      score (rho = 0.43; P = 0.005). CONCLUSION: Although the exact cause of increased
      CBD diameter with advancing age is not understood, a general atherosclerotic
      process which occurs with aging may affect smooth muscle of the CBD. Whether an
      upper limit for normal CBD should be defined or not when evaluating dilated CBD
      for patients with subclinical or clinical atherosclerosis needs further studies.

PMID- 29214446
TI  - UGT79B31 is responsible for the final modification step of pollen-specific
      flavonoid biosynthesis in Petunia hybrida.
AB  - MAIN CONCLUSION: UGT79B31 encodes flavonol 3- O -glycoside: 2"- O 
      glucosyltransferase, an enzyme responsible for the terminal modification of
      pollen-specific flavonols in Petunia hybrida. Flavonoids are known to be involved
      in pollen fertility in petunia (P. hybrida) and maize (Zea mays). As a first step
      toward elucidating the role of flavonoids in pollen, we have identified a
      glycosyltransferase that is responsible for the terminal modification of petunia
      pollen-specific flavonoids. An in silico search of the petunia transcriptome
      database revealed four candidate UDP-glycosyltransferase (UGT) genes. UGT79B31
      was selected for further analyses based on a correlation between the accumulation
      pattern of flavonol glycosides in various tissues and organs and the expression
      profiles of the candidate genes. Arabidopsis ugt79b6 mutants that lacked
      kaempferol/quercetin 3-O-glucosyl(1 -> 2)glucosides, were complemented by
      transformation with UGT79B31 cDNA under the control of Arabidopsis UGT79B6
      promoter, showing that UGT79B31 functions as a flavonol 3-O-glucoside: 2"-O
      glucosyltransferase in planta. Recombinant UGT79B31 protein can convert
      kaempferol 3-O-galactoside/glucoside to kaempferol 3-O-glucosyl(1 ->
      2)galactoside/glucoside. UGT79B31 prefers flavonol 3-O-galactosides to the 3-O
      glucosides and rarely accepted the 3-O-diglycosides as sugar acceptors. UDP
      glucose was the preferred sugar donor for UGT79B31. These results indicated that
      UGT79B31 encodes a flavonoid 3-O-glycoside: 2"-O-glucosyltransferase. Transient
      expression of UGT79B31 fused to green fluorescent protein (GFP) in Nicotiana
      benthamiana showed that UGT79B31 protein was localized in the cytosol.

PMID- 29214448
TI  - The role of dynamic post-contrast T1-w MRI sequence to characterize lipid-rich
      and lipid-poor adrenal adenomas in comparison to non-adenoma lesions: preliminary
      results.
AB  - PURPOSE: The purpose of the article is to compare the features of wash-out (WO)
      parameters between lipid-rich and lipid-poor adrenal adenomas as well as with a
      group of non-adenoma adrenal lesions. METHODS: 46 patients (36 F and 10 M, median
      age 58 years) with unilateral adrenal lesions (35 adenomas, 7 pheochromocytomas,
      1 carcinoma, and 3 metastases) were prospectively evaluated; adrenal lesions were
      divided into adenomas (Group 1) and non-adenomas (Group 2). MR imaging was
      performed with a 3-Tesla scanner using pre- and post-contrast dedicated
      sequences. On the basis of the evaluation of qualitative chemical-shift (CS)
      signal intensity (SI) loss, adrenal adenomas were, respectively, divided in Group
      1A (n = 25) as lipid-rich and Group 1B (n = 10) as lipid-poor; non-adenoma
      adrenal lesions were grouped in Group 2 (n = 11). The following parameters were
      evaluated: size (mm), CS SI index (%), early (5 min), and delayed (10 min)
      Relative (R) and Absolute (A) WO values (%). RESULTS: The comparison of AWO and
      RWO showed significant (p <= 0.05) differences between Group 1A and Groups 1B and
      2, both using 5- and 10-min images for calculation; conversely, no differences in
      these dynamic parameters were found between Group 1B and 2; AWO and RWO values
      were significantly lower in adrenal lesions of Groups 1B and 2 compared to Group
      1A, both using 5- and 10-min images for calculation. CONCLUSIONS: The
      quantitative evaluation of WO parameters could not be used to characterize lipid
      poor adrenal adenomas for which alternative imaging modalities are required.

PMID- 29214449
TI  - Celebrating the Annals of Surgical Oncology's 25-Year Anniversary: One of the
      Most Cited Surgical Journals in the World.

PMID- 29214450
TI  - Effects of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
      (HIPEC) in the Treatment of Goblet Cell Carcinoma: A Prospective Cohort Study.
AB  - BACKGROUND: Goblet cell carcinoma (GCC) of the appendix is a rare disease.
      Treatment options vary according to disease staging. Cytoreductive surgery in
      combination with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) may
      improve survival in patients with peritoneal spreading. OBJECTIVE: The aim of
      this study was to examine the prognosis of patients with appendiceal GCC treated
      per protocol, and to evaluate the results of CRS+HIPEC in cases of peritoneal
      spreading. METHODS: From 2009 to 2016, a total of 48 GCC patients were referred
      to the European Neuroendocrine Tumour Center of Excellence, Aarhus University
      Hospital. All patients received treatment per protocol according to disease
      staging. In patients with localized disease, the treatment was a right
      hemicolectomy. Patients with peritoneal spread who met the inclusion criteria for
      CRS + HIPEC, as well as patients with high-risk features of developing peritoneal
      spread, received CRS + HIPEC. If too-extensive disease was found, palliative
      chemotherapy was offered. RESULTS: Overall survival for patients with localized
      disease (n = 6) or deemed at risk of peritoneal spread (n = 8) was 100% after a
      median follow-up of 3.5 years. In patients with peritoneal spread and eligible
      for CRS+HIPEC(n = 27), the median survival was 3.2 years [95% confidence interval
      (CI) 2.3-4.1] and the 5-year survival rate was 57%. In contrast, the median
      survival for patients with too-extensive intraperitoneal disease (n = 7) was 1.3
      years (95% CI 0.6-2.0), with a 3-year survival rate of 20%. CONCLUSIONS: Long
      term survival can be achieved in patients with peritoneal spread treated with CRS
      + HIPEC. CRS+HIPEC was associated with a favorable outcome in GCC patients at
      high-risk of developing peritoneal spread.

PMID- 29214451
TI  - STMN1 is Overexpressed in Adrenocortical Carcinoma and Promotes a More Aggressive
      Phenotype In Vitro.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a
      poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic
      protein involved in microtubule dynamics through inhibition of tubulin
      polymerization and promotion of microtubule depolymerization, which has been
      implicated in carcinogenesis and aggressive behavior in multiple epithelial
      malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate
      how this may contribute to its malignant phenotype. METHODS: STMN1 was identified
      by RNA sequencing as a highly differentially expressed gene in human ACC samples
      compared with benign adrenal tumors. Expression was confirmed by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and
      immunohistochemical (IHC) staining of a tissue microarray (TMA) from two
      independent cohorts. The biologic relevance of STMN1 was investigated in NCI
      H295R cells by lentivirus-mediated silencing. RESULTS: Differential gene
      expression demonstrated an eightfold increase in STMN1 messenger RNA (mRNA) in
      malignant compared with benign adrenal tissue. IHC showed significantly higher
      expression of STMN1 protein in ACC compared with normal and benign tissues. STMN1
      knockdown in an ACC cell line resulted in decreased cell viability, cell-cycle
      arrest at G0/G1, and increased apoptosis in serum-starved conditions compared
      with scramble short hairpin RNA (shRNA) controls. STMN1 knockdown also decreased
      migration, invasion, and anchorage-independent growth compared with controls.
      CONCLUSIONS: STMN1 is overexpressed in human ACC samples, and knockdown of this
      target in vitro resulted in a less aggressive phenotype of ACC, particularly
      under serum-starved conditions. Further study is needed to investigate the
      feasibility of interfering with STMN1 as a potential therapeutic target.

PMID- 29214452
TI  - Moving Toward Improved Outcomes in Salvage Laryngectomy.

PMID- 29214453
TI  - Neoadjuvant Therapy Versus Upfront Resection for Pancreatic Cancer: The Actual
      Spectrum and Clinical Burden of Postoperative Complications.
AB  - BACKGROUND: Neoadjuvant therapy (NAT) is used for borderline-resectable or
      locally advanced pancreatic cancer (PDAC) and exhibits promising results in terms
      of pathological outcomes. However, little is known about its effect on surgical
      complications. METHODS: We analyzed 445 pancreatic resections for PDAC from 2014
      to 2016 at The Pancreas Institute, Verona University Hospital. The Modified
      Accordion Severity Grading System and average complication burden (ACB) were used
      to compare patients treated with NAT with patients who underwent upfront surgery
      (UFS). RESULTS: Of 305 pancreaticoduodenectomies (PD), patients treated with NAT
      (n = 99) had less pancreatic fistula (POPF, 9.1% vs. 15.6%, p = 0.05) without
      grade C cases, but grade B ACB was increased (0.28 for NAT vs. 0.24 for UFS, p =
      0.05). The postpancreatectomy hemorrhage (PPH) rate was lower in the NAT group
      (9.1% vs. 14.6%, p = 0.02), but ACB grades B (0.37 for NAT vs. 0.26 for UFS, p =
      0.03) and C (0.43 for NAT vs. 0.29 for UFS, p = 0.05) were increased. Delayed
      gastric emptying (DGE) was increased in NAT cases (15.2% vs. 8.3%, p = 0.04),
      with higher grade C ACB (0.43 for NAT vs. 0.29 for UFS, p = 0.03). Of 94 distal
      pancreatectomies (DP), NAT patients (n = 26) developed more grade C POPF (11.5%
      vs. 1.5%, p = 0.04) and DGE (11.5% vs. 2.9%, p = 0.01) without differences in
      ACB. CONCLUSIONS: Patients undergoing PD for PDAC after NAT exhibited reduced
      incidence of POPF and PPH but increased incidence of DGE compared with patients
      treated with UFS. Among patients developing postoperative complications after PD,
      those receiving NAT were associated with increased clinical burden.

PMID- 29214454
TI  - Impact of Sarcopenia on Unplanned Readmission and Survival After Esophagectomy in
      Patients with Esophageal Cancer.
AB  - BACKGROUND: Although sarcopenia increases postoperative complications following
      esophagectomy, its effects on prognosis remain unclear. This study was performed
      to identify the effect of sarcopenia on 90-day unplanned readmission and overall
      survival (OS) after esophagectomy. METHODS: Ninety-eight patients with esophageal
      cancer who underwent esophagectomy were enrolled in this study. Unplanned
      readmission was defined as any emergent hospitalization within 90 days after
      discharge. Sarcopenia, defined as low muscle mass plus low muscle strength and/or
      low physical performance according to the Asian consensus definition, was
      assessed prior to esophagectomy. Multivariate logistic regression analysis was
      performed to identify factors that contributed to 90-day unplanned readmission.
      OS was estimated using the Kaplan-Meier method, and a Cox proportional hazards
      model was used to assess the relationship between sarcopenia and OS. RESULTS:
      Thirty-one patients (31.6%) were diagnosed with sarcopenia. The 90-day unplanned
      readmission rate was significantly higher in patients with sarcopenia than those
      without (42.9% vs. 16.4%, respectively; p = 0.01). Multivariable logistic
      regression analysis showed that sarcopenia was an independent predictor of 90-day
      unplanned readmission [odds ratio 3.71, 95% confidence interval (CI) 1.29-11.05;
      p = 0.02], and the log-rank test showed that sarcopenia was associated with OS (p
      = 0.01). Moreover, sarcopenia was a significant predictor of OS after adjustment
      for age, sex, and pathological stage (hazard ratio 2.35, 95% CI 1.21-4.54; p =
      0.01). CONCLUSIONS: Sarcopenia is a risk factor for 90-day unplanned readmission
      and OS following esophagectomy. Assessment of sarcopenia could help to identify
      patients at higher risk of a poor prognosis after esophagectomy.

PMID- 29214455
TI  - Cryptococcus gattii Infection Presenting as an Aggressive Lung Mass.
AB  - Cryptococcus gattii is an endemic fungus predominantly isolated in the tropical
      and subtropical regions, causing predominantly pulmonary disease with a
      predilection for the central nervous system. Herein, we report a case of rapidly
      progressing C. gattii pneumonia in an immune-deficient but virologically
      suppressed host with underlying human immunodeficiency viral (HIV) infection,
      exhibiting various fungal morphologies from bronchoalveolar lavage (BAL)
      cytological specimens. A 51-year-old Chinese male with known HIV disease was
      admitted to the Singapore General Hospital for evaluation of functional decline,
      febrile episodes, and a left hilar mass on chest radiograph. Computed tomography
      (CT) showed consolidation in the apical segment of the left lower lobe. He
      underwent bronchoscopy and BAL. Positron emission tomography-computed tomography
      done 10 days after the initial CT showed approximate doubling of the pulmonary
      lesion. Cytological examination of the fluid revealed yeasts of varying sizes.
      Subsequent fungal culture from BAL fluid grew C. gattii 10 days later.

PMID- 29214456
TI  - Elastofibroma developing at the subscapular port site after thoracoscopic
      surgery: first case report.
AB  - In recent years, the number of cancer patients who undergo endoscopic surgery has
      been increasing, and port-site recurrence is becoming a more common complication.
      A 66-year-old woman underwent thoracoscopic left lower lobectomy with lymph node
      dissection for pT1aN0M0 adenocarcinoma of the lung. Six years after surgery, CT
      revealed a subscapular tumor measuring 3 cm at the site of the surgical port
      wound. Although port-site cancer recurrence was suspected, needle biopsy revealed
      that the tumor was an elastofibroma. During 6 months of follow-up, MRI revealed
      no further change, and it was concluded that development of the tumor at the
      subscapular port site had been merely coincidental.

PMID- 29214457
TI  - Gut Microbiota and Host Juvenile Growth.
AB  - Good genes, good food, good friends. That is what parents hope will sustain and
      nurture the harmonious growth of their children. The impact of the genetic
      background and nutrition on postnatal growth has been in the spot light for long,
      but the good friends have come to the scene only recently. Among the good friends
      perhaps the most crucial ones are those that we are carrying within ourselves.
      They comprise the trillions of microbes that collectively constitute each
      individual's intestinal microbiota. Indeed, recent epidemiological and field
      studies in humans, supported by extensive experimental data on animal models,
      demonstrate a clear role of the intestinal microbiota on their host's juvenile
      growth, especially under suboptimal nutrient conditions. Genuinely integrative
      approaches applicable to invertebrate and vertebrate systems combine tools from
      genetics, developmental biology, microbiology, nutrition, and physiology to
      reveal how gut microbiota affects growth both positively and negatively, in
      healthy and pathological conditions. It appears that certain natural or
      engineered gut microbiota communities can positively impact insulin/IGF-1 and
      steroid hormone signaling, thus contributing to the host juvenile development and
      maturation.

PMID- 29214458
TI  - The effects of uninvolved side epiphysiodesis for limb length equalization in
      children with unilateral cerebral palsy: clinical evaluation with the Edinburgh
      visual gait score.
AB  - PURPOSE: Hemiplegic cerebral palsy patient may present a shorten leg on the
      hemiplegic side that afflicts negatively the kinematic of the uninvolved limb.
      Thus, the aim of this study was to investigate the modification of gait kinematic
      after epiphysiodesis for limb equalization and secondary to verify the prediction
      of correction. METHODS: Skeletally immature hemiplegic patients with a minimum
      limb leg discrepancy (LLD) of 2.5 cm were treated with epiphysiodesis of the
      unaffected knee and clinically evaluated with Edinburgh visual gait score (EVGS).
      Green-Anderson curve was used to predict time decision for correction. RESULTS:
      Ten LLD patients were evaluated with the Edinburgh visual gait score (EVGS)
      before and after surgery. Mean age was 12.7 years, mean follow-up was 6.7 years,
      and mean LLD was 3.4 cm before surgery and 1.2 cm at final follow-up. After lower
      limb equalization surgery, improvement in gait kinematics was observed on both
      the uninvolved and hemiplegic limb of hemiplegic cerebral palsy patients (p <
      0.001). Final correction did not reach expected correction (2.3 vs. 2.8 cm).
      However, the difference was not statistically significant (p = 0.058).
      CONCLUSION: This is the first study to report improvement on both the uninvolved
      and hemiplegic limb gait kinematics after limb equalization surgery. Due to the
      impaired dorsiflexion of the hemiplegic foot, LLD target at the end of growth
      should range between 0.5 and 1.5 cm.

PMID- 29214459
TI  - The role of intraoperative cell salvage system on blood management in major
      orthopedic surgeries: a cost-benefit analysis.
AB  - INTRODUCTION: The aim of this study was to compare the efficiency and cost of
      cell salvage systems with allogeneic blood transfusions in patients who had major
      elective orthopedic surgeries. MATERIALS AND METHODS: Consecutive 108 patients
      who had intraoperative cell saver (CS) performed routinely constitute the study
      group. In control group, consecutive 112 patients who were operated without
      intraoperative CS were investigated. Hemoglobin (Hb) level less than 8 mg/dL was
      regarded as the absolute transfusion indication. The patients were evaluated for
      age, gender, body mass index, operation period, mean intraoperative estimated
      blood loss (EBL), postoperative hemovac drainage volume; preoperative,
      postoperative first day and discharge Hb levels, allogeneic blood transfusion
      (ABT) volume, hospitalization and cost parameters. RESULTS: The mean
      intraoperative EBL was 507 mL in the study group and 576 mL in control group. The
      mean ABT was 300 mL in the study group and 715 mL in control group. In the study
      group, intraoperative EBL, ABT usage and hospitalization period were
      significantly lower compared with the control group (p = 0.009, p = 0.000 and p =
      0.000; p < 0.05, respectively). The mean cost was 771 Turkish liras (TL) in the
      study group and 224 TL in control group. In the study group, the cost was
      significantly higher than the control group (p = 0.000). The postoperative first
      day Hb level was significantly higher in the study group (p = 0.010). CONCLUSION:
      Although CS usage was determined to increase the costs in this study, it
      significantly decreases intraoperative and postoperative ABT requirements. We
      believe that the increase in cost may be neglected when the complications and
      prolonged hospitalization due to ABT usage were regarded.

PMID- 29214460
TI  - Blood flow restriction late in recovery after heavy resistance exercise hampers
      muscle recuperation.
AB  - PURPOSE: This study aimed to examine the effect of acute blood flow restriction
      during the late recovery phase between two resistance exercise bouts on muscular
      endurance and oxygenation. METHODS: Amateur male middle- and long-distance
      runners performed two bouts of one-leg dynamic plantar flexion exercise to
      failure with the load equivalent to 75% of maximum. Subjects were randomly
      assigned into two experimental groups with thigh occlusion pressure between bouts
      at either 120 or 200 mmHg with 20 min of passive rest in between, and two control
      groups without any blood flow restriction separated by either 5 or 20 min of
      rest. Blood flow restriction in the experimental groups was implemented during
      the last 15 min of recovery. Calf arterial blood flow and muscle oxygenation were
      measured by venous occlusion plethysmography and near-infrared spectroscopy,
      respectively. RESULTS: Decrease of muscular oxygenation and blood flow during
      recovery between exercise bouts depended on the applied occlusion pressure. When
      compared with bout 1, work capacity in the experimental groups during bout 2 was
      reduced by 9.3 +/- 2.2% with 120 mmHg and by 10.5 +/- 3.1% (p < 0.05) with 200
      mmHg occlusion pressure. In the control groups, work capacity was restored after
      20 min (- 3.9 +/- 3.2%, p > 0.05) but not after 5-min recovery (- 20.0 +/- 1.8%,
      p < 0.05). CONCLUSIONS: Blood flow restriction late in recovery after a heavy
      resistance exercise bout decreased muscle oxygenation and work capacity during
      the subsequent heavy resistance exercise bout.

PMID- 29214462
TI  - The use of the CR-10 scale to allow self-regulation of isometric exercise
      intensity in pre-hypertensive and hypertensive participants.
AB  - PURPOSE: Isometric exercise (IE) has been shown to lower blood pressure (BP).
      Using equipment with force output displays, intensity is usually regulated at 30%
      maximal voluntary contraction (MVC); however, the cost of programmable equipment
      and their requirement for maximal contractions presents limitations. A simple,
      cost-effective alternative deserves investigation. The purpose of this study was
      (1) to explore the relationship between %MVC, change in systolic BP (DeltaSBP),
      and perceived exertion (CR-10) and (2) to assess the validity of self-regulation
      of intensity during isometric hand-grip exercise. METHODS: Fourteen pre
      hypertensive and hypertensive adults completed eight, 2-min isometric hand-grip
      exercises at randomised intensities; participants estimated their perceived
      exertion at 30-s intervals (estimation task). Subsequently, on three separate
      occasions, participants performed four 2-min contractions at an exertion level
      that they perceived to be equivalent to CR-10 "Level-6" (production task).
      RESULTS: There were significant linear relationships between the estimated
      exertion on the CR-10 scale, and DeltaSBP (r = 0.784) and %MVC (r = 0.845). Level
      6 was equivalent to an average DeltaSBP of 38 mmHg (95% CI; 44, 32 mmHg) and a
      relative force of 33% MVC (95% CI; 36.2, 30%). During the production task, %MVC
      was not significantly different between the estimation task and each production
      trial. In at least the first two repetitions of each production trial, DeltaSBP
      was significantly lower than that observed in the estimation task. CONCLUSION:
      These findings show that CR-10 "Level-6" is an appropriate method of self
      regulating isometric hand-grip intensity; its use offers an affordable and
      accessible alternative for isometric exercise prescription aimed at reducing BP.

PMID- 29214461
TI  - Co-ingestion of protein or a protein hydrolysate with carbohydrate enhances
      anabolic signaling, but not glycogen resynthesis, following recovery from
      prolonged aerobic exercise in trained cyclists.
AB  - PURPOSE: The effect of carbohydrate (CHO), or CHO supplemented with either sodium
      caseinate protein (CHO-C) or a sodium caseinate protein hydrolysate (CHO-H) on
      the recovery of skeletal muscle glycogen and anabolic signaling following
      prolonged aerobic exercise was determined in trained male cyclists [n = 11, mean
      +/- SEM age 28.8 +/- 2.3 years; body mass (BM) 75.0 +/- 2.3 kg; VO2peak 61.3 +/-
      1.6 ml kg-1 min-1]. METHODS: On three separate occasions, participants cycled for
      2 h at ~ 70% VO2peak followed by a 4-h recovery period. Isoenergetic drinks were
      consumed at + 0 and + 2 h of recovery containing either (1) CHO (1.2 g kg -1 BM),
      (2) CHO-C, or (3) CHO-H (1.04 and 0.16 g kg-1 BM, respectively) in a randomized,
      double-blind, cross-over design. Muscle biopsies from the vastus lateralis were
      taken prior to commencement of each trial, and at + 0 and + 4 h of recovery for
      determination of skeletal muscle glycogen, and intracellular signaling associated
      with protein synthesis. RESULTS: Despite an augmented insulin response following
      CHO-H ingestion, there was no significant difference in skeletal muscle glycogen
      resynthesis following recovery between trials. CHO-C and CHO-H co-ingestion
      significantly increased phospho-mTOR Ser2448 and 4EBP1 Thr37/46 versus CHO, with
      CHO-H displaying the greatest change in phospho-4EBP1 Thr37/46. Protein co
      ingestion, compared to CHO alone, during recovery did not augment glycogen
      resynthesis. CONCLUSION: Supplementing CHO with intact sodium caseinate or an
      insulinotropic hydrolysate derivative augmented intracellular signaling
      associated with skeletal muscle protein synthesis following prolonged aerobic
      exercise.

PMID- 29214463
TI  - Recreational football practice attenuates postprandial lipaemia in normal and
      overweight individuals.
AB  - INTRODUCTION: The aim of the present study was to examine the effects of playing
      football on postprandial lipaemia in normal and overweight individuals. METHODS:
      Fifteen (7 normal weight, age = 32.3 +/- 6.0 years, BMI = 22.8 +/- 3.4 kg/m2 and
      8 overweight, age = 33.3 +/- 5.5 years, BMI = 29.2 +/- 3.2 kg/m2, mean +/- SD)
      recreational football players were recruited. On the evening of day 1,
      participants played a 60-min 9-a-side football match (FOOT) or rested (control;
      CON) in a randomised counterbalanced cross-over design. Activity profile, heart
      rate and rate of perceived exertion were recorded. The next morning (> 10 h after
      the match), blood samples were collected before (0), 0.75, 2, 4, and 6 h after a
      high-fat meal. RESULTS: Total area under the curve for triglycerides were 22% and
      28% lower for the normal weight (p < 0.01; 95% CI - 2.45 to - 0.68; ES = 0.87)
      and overweight (p < 0.01; 95% CI - 8.14 to - 0.88; ES = 0.68) groups in the FOOT
      compared to the CON. The postprandial incremental area under the curve for
      triglycerides was 31% lower in the normal weight group (ES = 0.79) for the FOOT
      compared to CON trial and a discernible trend was shown for the overweight group
      (22%; ES = 0.51). Two-hour Insulin Sensitivity Index was lower (ES = - 0.95) for
      FOOT compared to CON trial in the overweight group only. CONCLUSION: Playing a 60
      min football match can attenuate the triglyceride response to a high-fat meal in
      normal and overweight individuals.

PMID- 29214464
TI  - Reliability of a semi-automated algorithm for the vastus lateralis muscle
      architecture measurement based on ultrasound images.
AB  - PURPOSE: The assessment of muscle architecture with B-mode ultrasound is an
      established method in muscle physiology and mechanics. There are several manual,
      semi-automated and automated approaches available for muscle architecture
      analysis from ultrasound images or videos. However, most approaches have
      limitations such as workload, subjectivity, drift or they are applicable to short
      muscle fascicles only. Addressing these issues, an algorithm was developed to
      analyse architectural parameters of the vastus lateralis muscle (VL). METHODS: In
      17 healthy young men and women, ultrasound images were taken five times on two
      different days during passive knee joint flexion. From the images, fascicle
      length (FL), pennation angle (PAN) and muscle thickness (MTH) were calculated for
      both test days using the algorithm. Interday differences were determined using a
      two-way ANOVA. Interday and intraday reliability were assessed using intraclass
      correlation coefficients (ICC) and root mean square (RMS) differences. RESULTS:
      FL, MTH and PAN did not differ between day one and two. The within day ICCs were
      above 0.94 for all tested parameters. The average interday ICCs were 0.86 for the
      FL, 0.96 for MTH and 0.60 for PAN. The average RMS differences between both days
      were 5.0%, 8.5% and 12.0% for MTH, FL and PAN, respectively. CONCLUSION: The
      proposed algorithm provides high measurement reliability. However, the interday
      reliability might be influenced by small differences in probe position between
      days.

PMID- 29214465
TI  - The peripheral soft tissues should not be ignored in the finite element models of
      the human knee joint.
AB  - In finite element models of the either implanted or intact human knee joint, soft
      tissue structures like tendons and ligaments are being incorporated, but usually
      skin, peripheral knee soft tissues, and the posterior capsule are ignored and
      assumed to be of minor influence on knee joint biomechanics. It is, however,
      unknown how these peripheral structures influence the biomechanical response of
      the knee. In this study, the aim was to assess the significance of the peripheral
      soft tissues and posterior capsule on the kinematics and laxities of human knee
      joint, based on experimental tests on three human cadaveric specimens. Despite
      the high inter-subject variability of the results, it was demonstrated that the
      target tissues have a considerable influence on posterior translational and
      internal and valgus rotational laxities of lax knees under flexion. Consequently,
      ignoring these tissues from computational models may alter the knee joint
      biomechanics.

PMID- 29214466
TI  - Large-scale DNA organization is a prognostic marker of breast cancer survival.
AB  - Breast cancer is the leading cause of cancer-related deaths among women
      worldwide. We investigated whether changes in large-scale DNA organization (LDO)
      of tumor epithelial nuclei are an indicator of the aggressiveness of the tumor.
      We tested our algorithm on a set of 172 duplicates TMA cores samples coming from
      95 breast cancer patients. Thirty-five patients died of breast cancer, and 60
      were still alive 10 years after surgery. Duplicates cores were used to create
      training and test set. The TMA slides were stained with Feulgen-thionin and
      imaged using our in-house high-resolution Imaging system. Automated segmentation
      of cell nuclei followed by manual selection of intact, in-focus nuclei resulted
      in an average of 50 cell nuclei per sample available for analysis. Using forward
      stepwise linear discriminant analysis, a combination of six features that
      combined linearly gave the best discrimination between the two groups of cells:
      cells collected from 'deceased' patients TMA specimens and cells collected from
      "survivors" patients TMA specimens. Five of these features measure the spatial
      organization of DNA chromatin. The resulting canonical score is named cell LDO
      score. A patient LDO score, percentage of cell nuclei with a cell LDO score
      higher than a predefined cutoff value, was processed for the specimens in the
      test set, and a cutoff value was defined to classify patients with a low or a
      high LDO score. Using this binary test, 82.1% of patients were correctly
      classified are "deceased" or "survivors," with a specificity of 79% and a
      sensitivity of 88%. The relative risk of death of an individual with a high LDO
      score was nine times higher than for a patient with a low LDO score. When testing
      the combination of LDO score, node status, histological grade, and tumor grade to
      predict breast cancer survival, LDO was the most significant predictor. LDO
      classification was also highly associated with survival for only grade 1 and 2
      patients as well as for only grade 3 patients. Our result confirms the potential
      of LDO to measure phenotypic changes associated with more aggressive disease and
      could be evaluated to identify patients more likely to benefit from adjuvant
      therapies.

PMID- 29214467
TI  - Different functional domains measured by cocaine self-administration under the
      progressive-ratio and punishment schedules in male Wistar rats.
AB  - BACKGROUND: Current diagnosis of drug addiction like other mental disorders is
      based on clinical symptoms not on neural pathophysiology and consequently, does
      not provide useful information on the underlying pathophysiology and may impede
      the efforts to identify the underlying mechanisms. Identifying the functional
      deficits that are relevant to addiction and can be traced to the neural systems
      will greatly facilitate our understanding of the heterogeneity of the condition
      and improve future diagnosis and treatment. Cocaine addiction is characterized by
      the continued use despite the dire consequences, and the deficit in inhibitory
      control may play a key role in this process. This study aimed to develop a
      paradigm to measure the punishment-induced inhibitory regulation of reward
      seeking behavior. METHODS: Rats were first trained to self-administer sucrose
      pellets under a chained schedule and then the breaking points (BPs) under the
      progressive-ratio schedule, and the intensity-response effects of footshock
      punishment on sucrose SA were measured. Subsequently, the rats went on to self
      administer intravenous cocaine, and the BPs and the punishment intensity-response
      effects were similarly determined. RESULTS: The areas under the punishment
      intensity-response curves (AUCs) were calculated and used as an indicator of the
      sensitivity of the inhibitory system. The BPs for cocaine were not correlated
      with the AUCs. Furthermore, the change in the BPs for cocaine induced by changing
      cocaine dose did not predict the change in the AUCs. CONCLUSION: The intensity
      response effects of punishment can be used to measure the function or sensitivity
      of the inhibitory system independent of the motivational state.

PMID- 29214468
TI  - Effects of acute alcohol and driving complexity in older and younger adults.
AB  - RATIONALE: Our previous work demonstrated differential neurobehavioral effects of
      low-dose alcohol consumption on older and younger adults in a driving simulator.
      However, the ability to enhance or suppress a response in such context has yet to
      be examined. OBJECTIVES: The current study contrasted older and younger drivers'
      responses to specific stimuli (i.e., relevant, irrelevant) in scenarios of
      differing complexity following low-dose acute alcohol administration. METHODS:
      Healthy older (55-70) and younger (25-35) adults completed two driving scenarios
      (i.e., country and metropolis) both before and after consuming beverages targeted
      to reach peak BrACs of 0.00, 0.04, or 0.065%. Throughout the simulation,
      participants encountered relevant stimuli (e.g., pedestrians walking into the
      street) and irrelevant stimuli (e.g., pedestrians walking parallel). Peak
      deceleration, range of steering, and distance until brake application were
      assessed within a 450-ft window preceding each stimulus. RESULTS: Following low
      dose alcohol consumption, older adults shifted from a strategy using both
      deceleration and steering to relying solely on deceleration in responding to
      relevant stimuli in the country. Older adults under both low and moderate alcohol
      conditions displayed an inability to withhold responses to irrelevant stimuli in
      the metropolis. CONCLUSION: These findings are consistent with our prior work
      showing differential effects of low-dose alcohol on older, relative to younger,
      adults. The interactive effects of age and alcohol, however, depend on stimulus
      type and environmental complexity. Continued investigation of neurobehavioral
      mechanisms in ecologically valid paradigms is necessary for understanding the
      implications of the combined impairing effects of alcohol and older age.

PMID- 29214469
TI  - Four-leaf clover-like bicuspid aortic valve visualized by two-dimensional
      thoracic and three-dimensional transesophageal echocardiography.

PMID- 29214470
TI  - Clinical and anti-aging effect of mud-bathing therapy for patients with
      fibromyalgia.
AB  - Spa bathing is known as a medical treatment for certain diseases causing chronic
      pains. Spa water contains mineral components which lower the specific heat of the
      water, resulting in a higher efficiency to warm body-core temperature. This
      phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain,
      sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological
      effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the
      changes of blood examination data, and the telomere length of circulating
      leukocytes. The enrolled 7 patients with fibromyalgia syndrome were hospitalized
      and were subject to daily mud bathing at 40  degrees C for 10 min for about a
      month. Then, their subjective pain was reduced to about a quarter in average.
      They also showed lowered serum triglyceride and C-reactive protein level,
      maintaining the levels of aspartate transaminase and creatine phosphokinase, and
      increases of the red blood cell count, the serum albumin level, and the serum LDL
      cholesterol level in comparison with cases without mud-bathing therapy,
      suggesting that mud bathing prevents inflammation and muscle atrophy and improves
      nutritional condition in fibromyalgia. In addition, the analysis of telomere
      length of peripheral leukocytes revealed a trend of negative correlation between
      telomere shortening and laboratory data change of hemoglobin and serum albumin.
      These telomeric changes can be explained hypothetically by an effect of mud
      bathing extending life-span of circulating leukocytes.

PMID- 29214471
TI  - Duration of the conditioning phase affects the results of plant-soil feedback
      experiments via soil chemical properties.
AB  - Plant-soil feedback (PSF) is a fundamental mechanism explaining plant community
      composition. Two-phase experiments, i.e., conditioning and feedback, represent a
      common methodology to study PSF. The duration of the conditioning phase varies
      among studies and the PSF observed is often explained by its biotic component.
      Little is known about the temporal variation of PSF and its abiotic component. As
      early life stages are crucial for plant establishment, we grew Rorippa austriaca
      in soil conditioned over 2, 4, 6 or 8 weeks by a conspecific or a co-occurring
      species, Agrostis capillaris. For each conditioning duration, we analysed the
      soil chemical properties and the direction and intensity of intra- or inter
      specific feedbacks. With increasing duration, the negative intra- and inter
      specific feedbacks became stronger and weaker, respectively. The inter-specific
      feedback was more negative than the intra-specific feedback at 2 weeks and this
      reversed thereafter. The Mg content decreased with conditioning duration whatever
      the conditioning species was. With increasing duration, conditioning by R.
      austriaca strongly decreased pH, while A. capillaris did not affect pH. The K and
      P contents were not affected by the conditioning duration and were higher in R.
      austriaca soil than in A. capillaris soil. Our results suggest that not only
      conditioning species but also duration of conditioning phase may affect the
      magnitude of PSF. The changes in soil chemical properties linked to the
      conditioning species or the conditioning phase duration may drive the feedbacks
      by affecting plant growth directly or via the interacting microbial communities.

PMID- 29214472
TI  - Host-choice reduces, but does not eliminate, the negative effects of a multi
      species diet for an herbivorous beetle.
AB  - A consequence of plant diversity is that it can allow or force herbivores to
      consume multiple plant species, which studies indicate can have major effects on
      herbivore fitness. An underappreciated but potentially important factor
      modulating the consequences of multi-species diets is the extent to which
      herbivores can choose their diets versus being forced to consume specific host
      plant sequences. We examined how host-selection behavior alters the effects of
      multi-species diets using the Colorado potato beetle (Leptinotarsa decemlineata)
      and diets of potato plants (Solanum tuberosum), tomato plants (S. lycopersicum),
      or both. When we gave beetles simultaneous access to both plants, allowing them
      to choose their diets, their final mass was within 0.1% of the average mass
      across both monocultures and 43.6% lower than mass on potato, the superior host
      in monoculture. This result indicates these beetles do not benefit from a mixed
      diet, and that the presence of tomato, an inferior but suitable host, makes it
      difficult to use potato. In contrast, when we forced beetles to switch between
      host species, their final mass was 37.8% less than the average of beetles fed
      constant diets of either host species and within 3.5% of the mass on tomato even
      though they also fed on potato. This indicates preventing host-selection behavior
      magnified the negative effects of this multi-species diet. Our results imply that
      ecological contexts that constrain host-selection or force host-switches, such as
      communities with competition or predation, will lead plant species diversity to
      reduce the performance of insect herbivores.

PMID- 29214473
TI  - Plants learn and remember: lets get used to it.

PMID- 29214474
TI  - Insufficient evidence for habituation in Mimosa pudica. Response to Gagliano et
      al. (2014).
AB  - Gagliano et al. (Oecologia 175(1):63-72, 2014) reported that Mimosa pudica
      habituates to repeated stimulation, as shown by a reduction in response,
      dishabituation, and stimulus specificity. I argue that Gagliano et al.'s data
      show an absence of dishabituation, that their experimental design needs an
      additional condition to test whether there is stimulus specificity, and that most
      of their data can be explained by motor fatigue. Some data are not easily
      explained by fatigue, and I suggest a further analysis that may clarify the
      issue. The status of habituation in Mimosa remains uncertain.

PMID- 29214475
TI  - Similar but not the same: metal concentrations in hair of three ecologically
      similar, forest-dwelling bat species (Myotis bechsteinii, Myotis nattereri, and
      Plecotus auritus).
AB  - Recently, a number of studies demonstrated the suitability of hair analysis to
      assess metal exposure of bats. As many bat species are endangered, such a non
      destructive method is particularly suited for this taxon. The present study
      analyzed the levels of two non-essential (cadmium and lead) and four essential
      metals (copper, manganese, molybdenum, and zinc) in hairs of three ecologically
      similar, sympatric bat species, Bechstein's bat (Myotis bechsteinii), Natterer's
      bat (Myotis nattereri), and Brown long-eared bat (Plecotus auritus) from an area
      in Central Hesse (Germany), as well as metal concentrations in soil samples from
      the bats' foraging habitats. Applying a previously established protocol, the
      analyses were performed using microwave-assisted extraction followed by
      inductively coupled plasma optical emission spectrometry. Cadmium and lead
      concentrations in hair did not differ significantly among the three studied
      species, whereas the following significant differences existed for levels of
      essential metals in hair. Manganese concentrations in hair were higher in M.
      bechsteinii and P. auritus than in M. nattereri and Cu concentrations were higher
      in M. nattereri than in P. auritus. Myotis bechsteinii showed higher Zn
      concentrations compared to P. auritus and lower Mo concentrations compared to M.
      nattereri. Reasons for the observed differences among the three studied species
      could be differential exposure to these metal elements in their foraging areas,
      related to variation in the species composition of their arthropod diet in
      combination with different metal levels in the respective prey species, and/or
      species-specific requirements for essential metals and related variation in
      physiological regulation of these elements in the bats.

PMID- 29214476
TI  - Acute effects of air pollution on spontaneous abortion, premature delivery, and
      stillbirth in Ahvaz, Iran: a time-series study.
AB  - Living in areas with high air pollution may have adverse effects on human health.
      There are few studies about the association between breathing polluted air and
      adverse pregnancy outcomes in the Middle East. The aim of this study was to
      determine the relationship between air pollution and spontaneous abortion,
      premature birth, and stillbirth in Ahvaz. A time-series study was conducted. Data
      about spontaneous abortion, premature deliveries, and stillbirth was collected
      from Ahvaz Imam Khomeini Hospital. Air pollution data including NO, CO, NO2,
      PM10, SO2, O3, and climate data were, respectively, collected from the
      Environmental Protection Agency and the Khuzestan Province Meteorology Office
      from March 2008 until March 2015. The relationship between air pollutants with
      the number of abortions, premature births, and stillbirths was found using a
      quasi-Poisson distributed lag model, adjusted by trend, seasonality, temperature,
      relative humidity, weekdays, and holidays. The average daily dust in Ahvaz on
      7.2% days of the year was higher than 500 MUg/m3 (very dangerous). Findings from
      this study indicate a significant association between each 10-unit increase in
      SO2 and spontaneous abortion in lag 0 and 9 days. There was a significant
      relation between each 10-unit increase in NO2 and CO, and premature birth in lag
      0. Also, we found a significant association between each 10-unit increase in CO
      and premature delivery in lag 1; PM10 and premature delivery in lags 10, 11, and
      12; and NO and premature delivery in lags 3, 4, 10, 11, 12, and 13 (p value <
      0.05). Contact with polluted air during pregnancy may increase adverse pregnancy
      outcomes and stillbirth. Pregnant women should avoid polluted air.

PMID- 29214477
TI  - Prevalence of occult hepatitis C virus among hemodialysis patients in Tanta
      university hospitals: a single-center study.
AB  - Occult hepatitis C virus infection (OCI) is a newly defined type of infection by
      the chronic hepatitis virus (HCV) distinguished by the existence of HCV RNA in
      liver tissue and/or peripheral blood mononuclear cells (PBMCs) in patients whose
      plasma are devoid of both positive serology and RNA. Patients on maintenance
      hemodialysis evince a higher HCV prevalence than the general population due to
      high nosocomial transmission by the dialysis units. We investigated the
      prevalence of occult HCV infection in patients attending our university
      hemodialysis centers for maintenance hemodialysis. Sixty-two CHD patients
      negative for serum HCV tests were enrolled in the study. PMNCs were tested by
      real-time PCR for the presence of HCV RNA. For the 62 patients, the average
      duration since starting dialysis was 32.7 months and the mean (SD) alanine
      transaminase and aspartate transaminase were 25.74 +/- 9.75 and 28.81 +/- 11.32
      IU/l, respectively. Out of the 62 CHD patients negative for serum anti-HCV and
      HCV RNA patients, only three (4.84%) were shown to have HCV RNA in their PBMCs
      implying the diagnosis of OCI; their viral load range was 1.24-4.15 IU/ml. All
      three OCI-proven patients gave no history of hepatic disease. In this study, we
      found that patients considered to be free of HCV can have HCV replicating in
      their PBMCs. This awareness points to the possibility of HCV being transmitted
      from apparently uninfected persons. A positive HCV RNA detection in PBMCs is
      dependable in determining OCI among high-risk subjects particularly when a liver
      biopsy is not an option. HCV transmission can occur through hemodialysis units
      signaling incorrect application of infection control measures in our Egyptian
      dialysis units. Additional studies on hemodialysis patients are necessary to
      realize the true magnitude of OCI among this patient group and to highlight the
      importance of incorporating HCV viral assays in PBMCs into the diagnostic
      algorithm.

PMID- 29214478
TI  - Cigarette butts abundance and association of mercury and lead along the Persian
      Gulf beach: an initial investigation.
AB  - The toxic metal contents of cigarette butts and distribution of cigarette butts
      have not been studied well in maritime environment. In the present study,
      cigarette butts distribution and the associations of Hg and Pb from cigarette
      butts were monitored along the Persian Gulf with 10 days interval sampling time.
      The number of cigarette butts, and Hg and Pb associations of butts were found to
      vary widely between 2 and 38 items per square meter, 2.5 and 86.32 ng/g cigarette
      butt (CB), as well as 650 and 8630 ng/g CB, respectively. Wilcoxon signed-rank
      test showed that there were no significant differences between the number of
      butts, and Hg and Pb contents of the butts at different sampling times.
      Considering amount of cigarette butts littered yearly, this study demonstrates
      that remarkable toxic metals of Hg and Pb may enter maritime environment each
      year and may introduce critical hazards to aquatic organisms, enter food chain,
      and finally human body.

PMID- 29214479
TI  - Cities of the future-bionic systems of new urban environment.
AB  - The concepts of the cities we know nowadays, and which we are accustomed to,
      change at a very rapid pace. The philosophy of their design is also changing. It
      will base on new standards, entering a completely different, futuristic
      dimension. This stage is related to changes in the perception of space, location
      and lack of belonging to definite, national or cultural structures. Cities of the
      future are cities primarily intelligent, zero-energetic, zero-waste,
      environmentally sustainable, self-sufficient in terms of both organic food
      production and symbiosis between the environment and industry. New cities will be
      able to have new organisational structures-either city states, or, apolitical,
      jigsaw-like structures that can change their position-like in the case of the
      city of Artisanopolis, designed as a floating city, close to the land,
      reminiscent of the legendary Atlantis. This paper is focused on the main issues
      connected with problems of the contemporary city planning. The purpose of the
      research was to identify existing technological solutions, whose aim is to use
      solar energy and urban greenery. The studies were based on literature related to
      future city development issues and futuristic projects of the architects and city
      planners. In the paper, the following issues have been verified: futuristic
      cities and districts, and original bionic buildings, both residential and
      industrial. The results of the analysis have been presented in a tabular form.

PMID- 29214480
TI  - Amicarbazone degradation promoted by ZVI-activated persulfate: study of relevant
      variables for practical application.
AB  - Alarming amounts of organic pollutants are being detected in waterbodies due to
      their ineffective removal by conventional treatment techniques, which warn of the
      urgent need of developing new technologies for their remediation. In this
      context, advanced oxidation processes (AOPs), especially those based on Fenton
      reactions, have proved to be suitable alternatives, due to their efficacy of
      removing persistent organic compounds. However, the use of ferrous iron in these
      processes has several operational constraints; to avoid this, an alternative iron
      source was here investigated: zero-valent-iron (ZVI). A Fenton-like process based
      on the activation of a recently explored oxidant-persulfate (PS)-with ZVI was
      applied to degrade an emerging contaminant: Amicarbazone (AMZ). The influence of
      ZVI size and source, PS/ZVI ratio, pH, UVA radiation, dissolved O2, and inorganic
      ions was evaluated in terms of AMZ removal efficiency. So far, this is the first
      time these parameters are simultaneously investigated, in the same study, to
      evaluate a ZVI-activated PS process. The radical mechanism was also explored and
      two radical scavengers were used to determine the identity of major active
      species taking part in the degradation of AMZ. The degradation efficiency was
      found to be strongly affected by the ZVI dosage, while positively affected by the
      PS concentration. The PS/ZVI system enabled AMZ degradation in a wide range of
      pH, although with a lower efficiency under slightly alkaline conditions.
      Dissolved O2 revealed to play an important role in reaction kinetics as well as
      the presence of inorganic ions. UVA radiation seems to improve the degradation
      kinetics only in the presence of extra O2 content. Radicals quenching experiments
      indicated that both sulfate (SO4*-) and hydroxyl (*OH) radicals contributed to
      the overall oxidation performance, but SO4*- was the dominant oxidative species.

PMID- 29214481
TI  - Environmental levels of triclosan and male fertility.
AB  - Triclosan is a synthetic chemical with broad antimicrobial activity that has been
      used extensively in consumer products, including personal care products,
      textiles, and plastic kitchenware, although the exposure which is widespread
      evidence from human studies is scarce. Our study aims to investigate the
      relationship between triclosan exposure and male fertility. Triclosan (TCS)
      urinary concentrations were measured using gas chromatography coupled with tandem
      mass spectrometry in 315 men recruited from a male reproductive health clinic
      with normal sperm concentration (>= 15 mln/ml) (WHO 2010) under 45 years of age.
      Participants were interviewed and provided a semen sample. TCS was detected in
      84.13% of urine samples, with a median concentration of 2.83 MUg/l (2.57 MUg/g
      creatinine). A multiple linear regression analysis showed a positive association
      between the urinary concentrations of triclosan 50th-75th percentile and >= 50
      percentile and percentage of sperm with abnormal morphology (p = 0.016 and p =
      0.002, respectively). The study provides evidence that exposure to triclosan is
      associated with poorer semen quality. Future studies are needed to confirm these
      findings.

PMID- 29214482
TI  - Characteristics of different molecular weight EPS fractions from mixed culture
      dominated by AnAOB and their role in binding metal ions.
AB  - Ultraviolet-visible (UV-Vis) absorbance spectra were adopted to quantify the
      binding of metal ions (e.g., Fe(III), Cu(II), Pb(II), and Cd(II)) on three MW
      fractions (> 100, 10~100, and < 10 k Da) of extracellular polymeric substances
      (EPS) extracted from mixed cultures dominated by anaerobic ammonium-oxidizing
      bacteria (AnAOB). The results showed that the AnAOB EPS with different MW size
      ranges all had strongest binding capability of Fe(III), and the lowest binding
      capability of Cd(II). The complexation ability of metal ions for the EPS of AnAOB
      with molecular weight < 10 kDa was stronger than EPS with >100 and 10~100 kDa,
      very likely because of the contribution of the tyrosine-, tryptophan-, and
      aromatic protein-like components. It was obvious that the different size
      fractions of EPS affect the metal binding ability. Essentially, the content of
      proteins, polysaccharides, TOC, and UVA254 distributed within various MW
      fractions of EPS from AnAOB were different, as well as the different fluorescent
      components and total functional groups.

PMID- 29214484
TI  - Designing Neat and Composite Carbon Nanotube Materials by Porosimetric
      Characterization.
AB  - We propose a porosimetry-based method to characterize pores formed by carbon
      nanotubes (CNTs) in the CNT agglomerates for designing neat CNT-based materials
      and composites. CNT agglomerates contain pores between individual CNTs and/or CNT
      bundles (micropore < 2 nm, mesopores 2-50 nm, and macropores > 50 nm). We
      investigated these pores structured by CNTs with different diameters and number
      of walls, clarifying the broader size distribution and the larger volume with
      increased diameters and number of walls. Further, we demonstrated that CNT
      agglomerate structures with different bulk density were distinguished depending
      on the pore sizes. Our method also revealed that CNT dispersibility in solvent
      correlated with the pore sizes of CNT agglomerates. By making use of these
      knowledge on tailorable pores for CNT agglomerates, we successfully found the
      correlation between electrical conductivity for CNT rubber composites and pore
      sizes of CNT agglomerates. Therefore, our method can distinguish diverse CNT
      agglomerate structures and guide pore sizes of CNT agglomerates to give high
      electrical conductivity of CNT rubber composites.

PMID- 29214483
TI  - PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with
      prefrontal transcranial direct current stimulation (tDCS) in major depressive
      disorder-study design and methodology of a multicenter double-blind randomized
      placebo-controlled trial.
AB  - Major Depressive Disorder (MDD) is one of the most prevalent psychiatric
      disorders worldwide. About 20-30% of patients do not respond to the standard
      psychopharmacological and/or psychotherapeutic interventions. Mounting evidence
      from neuroimaging studies in MDD patients reveal altered activation patterns in
      lateral prefrontal brain areas. Successful cognitive behavioral therapy (CBT) is
      associated with a recovery of these neural alterations. Moreover, it has been
      demonstrated that transcranial direct current stimulation (tDCS) is capable of
      influencing prefrontal cortex activity and cognitive functions such as working
      memory and emotion regulation. Thus, a clinical trial investigating the effects
      of an antidepressant intervention combining CBT with tDCS seems promising. The
      present study investigates the antidepressant efficacy of a combined CBT-tDCS
      intervention as compared to CBT with sham-tDCS or CBT alone. A total of 192
      patients (age range 20-65 years) with MDD (Hamilton Depression Rating Scale Score
      >= 15, 21-item version) will be recruited at four study sites across Germany
      (Berlin, Munich, Tuebingen, and Freiburg) and randomly assigned to one of the
      following three treatment arms: (1) CBT + active tDCS; (2) CBT + sham-tDCS; and
      (3) CBT alone. All participants will attend a 6-week psychotherapeutic
      intervention comprising 12 sessions of CBT each lasting 100 min in a closed group
      setting. tDCS will be applied simultaneously with CBT. Active tDCS includes
      stimulation with an intensity of 2 mA for 30 min with the anode placed over F3
      and the cathode over F4 according to the EEG 10-20 system, if assigned. The
      primary outcome measure is the change in Montgomery-Asberg Depression Rating
      Scale scores from baseline to 6, 18, and 30 weeks after the first session.
      Participants also undergo pre- and post-treatment neuropsychological testing and
      functional magnetic resonance imaging (fMRI) to assess changes in prefrontal
      functioning and connectivity. The study investigates whether CBT can be augmented
      by non-invasive brain stimulation techniques such as tDCS in the treatment of
      MDD. It is designed as a proof-of-principle trial for the combined tDCS-CBT
      treatment, but also allows the investigation of the neurobiological underpinnings
      of the interaction between both interventions in MDD. Trial registration
      ClinicalTrials.gov Identifier NCT02633449.

PMID- 29214485
TI  - Two-Phase Contrast Injection Protocol for Pediatric Cardiac Computed Tomography
      in Children with Congenital Heart Disease.
AB  - To assess a two-phase contrast injection protocol for contrast enhancement during
      cardiac computed tomography (CT) in children with congenital heart disease. Forty
      three children (20 boys, 23 girls) of median age 13 months (range 3 days-8.3
      years) and weighing <= 20 kg who underwent cardiac CT using a two-phase contrast
      injection protocol at our institution were retrospectively identified. High-pitch
      spiral third-generation dual-source cardiac CT (tube voltage 70 kV) was performed
      with a fixed delay of 60 s after contrast injection in the order of 10 mgI/kg/s
      (30 s), 15 mgI/kg/s (20 s), and a saline chaser (10 s). Attenuation in the
      inferior vena cava (IVC), superior vena cava (SVC), right atrium (RA), right
      ventricle (RV), pulmonary artery (PA), left atrium (LA), left ventricle (LV), and
      descending aorta (AO) was compared using the Steel-Dwass and Fisher's exact
      tests. The median (interquartile range) attenuation in the IVC, SVC, RA, RV, PA,
      LA, LV, and AO was 285 (264-347) Hounsfield units (HU), 416 (370-445) HU, 368
      (320-388) HU, 373 (322-417) HU, 397 (330-432) HU, 425 (373-469) HU, 435 (385-468)
      HU, and 437 (392-491) HU, respectively (p < 0.05, IVC vs. the other anatomic
      sites). There was no significant difference in diagnostic success rate for
      attenuation > 250 HU between the IVC (41 children, 95.3%) and the other sites (43
      children, 100%). A two-phase contrast injection protocol is useful for effective
      contrast enhancement in pediatric cardiac CT.

PMID- 29214486
TI  - Metabolism-mediated induction of zinc tolerance in Brassica rapa by Burkholderia
      cepacia CS2-1.
AB  - Brassica rapa (Chinese cabbage) is an essential component of traditional Korean
      food. However, the crop is often subject to zinc (Zn+) toxicity from contaminated
      irrigation water, which, as a result, compromises plant growth and production, as
      well as the health of human consumers. The present study investigated the
      bioaccumulation of Zn+ by Burkholderia cepacia CS2-1 and its effect on the heavy
      metal tolerance of Chinese cabbage. Strain CS2-1 was identified and characterized
      on the basis of 16S rRNA sequences and phylogenetic analysis. The strain actively
      produced indole-3-acetic acid (3.08 +/- 0.21 MUg/ml) and was also able to produce
      siderophore, solubilize minerals, and tolerate various concentrations of Zn+. The
      heavy metal tolerance of B. rapa plants was enhanced by CS2-1 inoculation, as
      indicated by growth attributes, Zn+ uptake, amino acid synthesis, antioxidant
      levels, and endogenous hormone (ABA and SA) synthesis. Without inoculation, the
      application of Zn+ negatively affected the growth and physiology of B. rapa
      plants. However, CS2-1 inoculation improved plant growth, lowered Zn+ uptake,
      altered both amino acid regulation and levels of flavonoids and phenolics, and
      significantly decreased levels of superoxide dismutase, endogenous abscisic acid,
      and salicylic acid. These findings indicate that B. cepacia CS2-1 is suitable for
      bioremediation against Zn+-induced oxidative stress.

PMID- 29214487
TI  - Effects of dietary poly-beta-hydroxybutyrate (PHB) on microbiota composition and
      the mTOR signaling pathway in the intestines of litopenaeus vannamei.
AB  - Poly-beta-hydroxybutyrate (PHB) is a natural polymer of the short chain fatty
      acid beta-hydroxybutyrate, which acts as a microbial control agent. The mammalian
      target of the rapamycin (mTOR) signaling pathway plays a crucial role in
      intestine inflammation and epithelial morphogenesis. In this study, we examined
      the composition of intestine microbiota, and mTOR signaling-related gene
      expression in Pacific white shrimp Litopenaeus vannamei fed diets containing
      different levels of PHB: 0% (Control), 1% (PHB1), 3% (PHB3), and 5% (PHB5) (w/w)
      for 35 days. High-throughput sequencing analysis revealed that dietary PHB
      altered the composition and diversity of intestine microbiota, and that the
      microbiota diversity decreased with the increasing doses of PHB. Specifically,
      dietary PHB increased the relative abundance of Proteobacteria and Tenericutes in
      the PHB1 and PHB5 groups, respectively, and increased that of Gammaproteobacteria
      in the three PHB groups. Alternatively, PHB decreased Alphaproteobacteria in the
      PHB3 and PHB5 groups. At the genus level, dietary PHB increased the abundance of
      beneficial bacteria, such as Bacillus, Lactobacillus, Lactococcus, Clostridium,
      and Bdellovibrio. The relative mRNA expression levels of the mTOR signaling
      related genes TOR, 4E-BP, eIF4E1alpha, and eIF4E2 all increased in the three PHB
      treatment groups. These results revealed that dietary PHB supplementation had a
      beneficial effect on intestine health of L. vannamei by modulating the
      composition of intestine microbiota and activating mTOR signaling.

PMID- 29214488
TI  - Electron microscopic observations of prokaryotic surface appendages.
AB  - Prokaryotic microbes possess a variety of appendages on their cell surfaces. The
      most commonly known surface appendages of bacteria include flagella, pili, curli,
      and spinae. Although archaea have archaella (archaeal flagella) and various types
      of pili that resemble those in bacteria, cannulae, and hami are unique to
      archaea. Typically involved in cell motility, flagella, the thickest appendages,
      are 20-26 nm and 10-14 nm wide in bacteria and archaea, respectively. Bacterial
      and archaeal pili are distinguished by their thin, short, hair-like structures.
      Curli appear as coiled and aggregative thin fibers, whereas spinae are tubular
      structures 50-70 nm in diameter in bacteria. Cannulae are characterized by ~25 nm
      wide tubules that enter periplasmic spaces and connect neighboring archaeal
      cells. Hami are 1-3 MUm in length and similar to barbed grappling hooks for
      attachment to bacteria. Recent advances in specimen preparation methods and image
      processing techniques have made cryo-transmission electron microscopy an
      essential tool for in situ structural analysis of microbes and their
      extracellular structures.

PMID- 29214489
TI  - Direct interaction between the transcription factors CadC and OmpR involved in
      the acid stress response of Salmonella enterica.
AB  - In Salmonella enterica serovar Typhimurium, the acid-sensing regulator CadC
      activates transcription of the cadBA operon which contributes to the acid
      tolerance response. The DNA-binding response regulator OmpR in two-component
      regulatory system with EnvZ binds to its own promoter for autoinduction. We
      previously reported that CadC exerts a negative influence on ompR transcription
      during acid adaptation. However, its underlying mechanisms remain to be
      elucidated. Here we show that the level of OmpR protein is gradually reduced by a
      gradual increase in the CadC level using an arabinose-inducible expression
      system, indicating there exists a negative correlation between the expression
      levels of two transcription factors. To explore the molecular basis for OmpR
      repression by CadC, we performed in vitro binding assays and determined that CadC
      directly interacts with OmpR. We further show that inactivation of cadC inhibits
      transcription of the fliC gene, which encodes the major flagellar subunit,
      resulting in impaired flagellar motility under acid-adaptation conditions.
      Together, our findings suggest that CadC may repress autoinduction of the OmpR
      response regulator through their direct interaction.

PMID- 29214490
TI  - Spirosoma migulaei sp. nov., isolated from soil.
AB  - A Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, aerobic
      bacterium, designated 15J9-8T, was isolated from soil on Jeju Island, Republic of
      Korea. The isolate was able to grow between 10 and 30 degrees C, pH 6.5-8.5, and
      in presence of 0-1% (w/v) NaCl. The results of comparative 16S rRNA gene sequence
      analysis indicated that strain 15J9-8T represented a member of the family
      Cytophagaceae, phylum Bacteroidetes, and was most closely related to Spirosoma
      aerophilum 5516J-17T (96.1% similarity), Spirosoma pulveris JSH5-14T (95.6%), and
      Spirosoma linguale DSM 74T (95.2%). The G + C content of the genomic DNA of the
      isolate was 47.0 mol%. Strain 15J9-8T contained summed feature 3 (C16:1
      omega7c/C16:1 omega6c), C16:1 omega5c, and iso-C15:0 as the major fatty acids,
      phosphatidylethanolamine and an unidentified aminophospholipid as the main polar
      lipids, and menaquinone MK-7 as the predominant respiratory quinone. On the basis
      of its phenotypic and genotypic properties, and phylogenetic distinctiveness,
      strain 15J9-8T should be classified as a representative of a novel species of the
      genus Spirosoma, for which the name Spirosoma migulaei sp. nov. is proposed. The
      type strain is 15J9-8T (=KCTC 52028T =JCM 31996T).

PMID- 29214491
TI  - Cecal microbiome divergence of broiler chickens by sex and body weight.
AB  - The divergence of gut bacterial community on broiler chickens has been reported
      as potentially possible keys to enhancing nutrient absorption, immune systems,
      and increasing poultry health and performance. Thus, we compared cecal bacterial
      communities and functional predictions by sex and body weight regarding the
      association between cecal microbiota and chicken growth performance. In this
      study, a total of 12 male and 12 female 1-day-old broiler chickens were raised
      for 35 days in 2 separate cages. Chickens were divided into 3 subgroups depending
      on body weight (low, medium, and high) by each sex. We compared chicken cecal
      microbiota compositions and its predictive functions by sex and body weight
      difference. We found that bacterial 16S rRNA genes were classified as 3 major
      phyla (Bacteroidetes, Firmicutes, and Proteobacteria), accounting for > 98% of
      the total bacterial community. The profiling of different bacterial taxa and
      predictive metagenome functions derived from 16S rRNA genes were performed over
      chicken sex and bodyweight. Male chickens were related to the enrichment of
      Bacteroides while female chickens were to the enrichment of Clostridium and
      Shigella. Male chickens with high body weight were associated with the enrichment
      of Faecalibacterium and Shuttleworthia. Carbohydrate and lipid metabolisms were
      suggested as candidate functions for weight gain in the males. This suggests that
      the variation of cecal bacterial communities and their functions by sex and body
      weight may be associated with the differences in the growth potentials of broiler
      chickens.

PMID- 29214492
TI  - An ethanol extract of Lysimachia mauritiana exhibits inhibitory activity against
      hepatitis E virus genotype 3 replication.
AB  - Hepatitis E virus (HEV) is an etiological agent of acute hepatitis E, a self
      limiting disease prevalent in developing countries. HEV can cause fulminant
      hepatic failure with high mortality rates in pregnant women, and genotype 3 is
      reported to trigger chronic hepatitis in immunocompromised individuals worldwide.
      Screening of plant extracts for compounds with potential anti-HEV effects led to
      the identification of a 70% ethanol extract of Lysimachia mauritiana (LME) that
      interferes with replication of the swine HEV genotype 3 replicon. Furthermore,
      LME significantly inhibited replication of HEV genotype 3 and expression of HEV
      ORF2 in infected cells without exerting cytotoxic effects. Collectively, our
      findings demonstrate the potential utility of LME in the development of novel
      antiviral drugs against HEV infection.

PMID- 29214493
TI  - Virgibacillus kimchii sp. nov., a halophilic bacterium isolated from kimchi.
AB  - A Gram-stain-positive, halophilic, rod-shaped, non-motile, spore forming
      bacterium, strain NKC1-2T, was isolated from kimchi, a Korean fermented food.
      Comparative analysis based on 16S rRNA gene sequence demonstrated that the
      isolated strain was a species of the genus Virgibacillus. Strain NKC1-2T
      exhibited high level of 16S rRNA gene sequence similarity with the type strains
      of Virgibacillus xinjiangensis SL6-1T (96.9%), V. sediminis YIM kkny3T (96.8%),
      and V. salarius SA-Vb1T (96.7%). The isolate grew at pH 6.5-10.0 (optimum, pH 8.5
      9.0), 0.0-25.0% (w/v) NaCl (optimum, 10-15% NaCl), and 15-50 degrees C (optimum,
      37 degrees C). The major menaquinone in the strain was menaquinone-7, and the
      main peptidoglycan of the strain was meso-diaminopimelic acid. The predominant
      fatty acids of the strain were iso-C14:0, anteisio-C15:0, iso- C15:0, and iso
      C16:0 (other components were < 10.0%). The polar lipids consisted of
      diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G + C content of
      NKC1-2T was 42.5 mol%. On the basis of these findings, strain NKC1-2T is proposed
      as a novel species in the genus Virgibacillus, for which the name Virgibacillus
      kimchii sp. nov. is proposed (=KACC 19404T =JCM 32284T). The type strain of
      Virgibacillus kimchii is NKC1-2T.

PMID- 29214494
TI  - Guinea pig complement potently measures vibriocidal activity of human antibodies
      in response to cholera vaccines.
AB  - The vibriocidal assay using guinea pig complement is widely used for the
      evaluation of immune responses to cholera vaccines in human clinical trials.
      However, it is unclear why guinea pig complement has been used over human
      complement in the measurement of vibriocidal activity of human sera and there
      have not been comparison studies for the use of guinea pig complement over those
      from other species. Therefore, we comparatively investigated the effects of
      complements derived from human, guinea pig, rabbit, and sheep on vibriocidal
      activity. Complements from guinea pig, rabbit, and human showed concentration
      dependent vibriocidal activity in the presence of quality control serum
      antibodies. Of these complements, guinea pig complement was the most sensitive
      and effective over a wide concentration range. When the vibriocidal activity of
      complements was measured in the absence of serum antibodies, human, sheep, and
      guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1
      fold dilution, respectively. For human pre- and post-vaccination sera, the most
      potent vibriocidal activity was observed when guinea pig complement was used. In
      addition, the highest fold-increases between pre- and post- vaccinated sera were
      obtained with guinea pig complement. Furthermore, human complement contained a
      higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than
      guinea pig complement. Collectively, these results suggest that guinea pig
      complements are suitable for vibriocidal assays due to their high sensitivity and
      effectiveness to human sera.

PMID- 29214496
TI  - Erratum to: Application of high-resolution melting analysis for differentiation
      of spoilage yeasts.
AB  - In the article by Erdem et al. published in Journal of Microbiology 2016; 54, 618
      625, the figure 1 should be corrected as below.

PMID- 29214495
TI  - Comparison of anti-influenza virus activity and pharmacokinetics of oseltamivir
      free base and oseltamivir phosphate.
AB  - Influenza viruses are major human respiratory pathogens that cause high morbidity
      and mortality worldwide. Currently, prophylactic vaccines and therapeutic
      antiviral agents are used to prevent and control influenza virus infection.
      Oseltamivir free base (OSV-FB), a modified generic antiviral drug of Tamiflu
      (oseltamivir phosphate, OSV-P), was launched in the Republic of Korea last year.
      Here, we examine the bioequivalence of these two compounds by assessing their
      antiviral efficacy in infected cells and in a mouse model. It was observed that
      both antivirals showed comparable efficacy against 11 different influenza A and B
      viruses in vitro. Moreover, in mice infected with influenza A virus (mouse
      adapted A/Puerto Rico/8/34), they showed a dose-dependent therapeutic activity
      and alleviated infection-mediated reductions in body weight, leading to
      significantly better survival. There was histopathological disappearance of virus
      induced inflammatory cell infiltration of the lung after oral treatment with
      either antiviral agent (at 10 mg/kg). Pharmacokinetic analysis also exhibited
      similar plasma concentrations of the active drug, oseltamivir carboxylate,
      metabolised from both OSV-B and OSV-P. This is the first report showing
      bioequivalence of OSV-FB to its phosphate salt form in the mouse system. The free
      base drug has some beneficial points including simple drug formulation process
      and reduced risk of undesirable cation-phosphate precipitation within solution.
      The long term stability of OSV-FB requires further monitoring when it is provided
      as a national stock in readiness for an influenza pandemic.

PMID- 29214497
TI  - Comparing Reverse Complementary Genomic Words Based on Their Distance
      Distributions and Frequencies.
AB  - In this work, we study reverse complementary genomic word pairs in the human DNA,
      by comparing both the distance distribution and the frequency of a word to those
      of its reverse complement. Several measures of dissimilarity between distance
      distributions are considered, and it is found that the peak dissimilarity works
      best in this setting. We report the existence of reverse complementary word pairs
      with very dissimilar distance distributions, as well as word pairs with very
      similar distance distributions even when both distributions are irregular and
      contain strong peaks. The association between distribution dissimilarity and
      frequency discrepancy is also explored, and it is speculated that symmetric pairs
      combining low and high values of each measure may uncover features of interest.
      Taken together, our results suggest that some asymmetries in the human genome go
      far beyond Chargaff's rules. This study uses both the complete human genome and
      its repeat-masked version.

PMID- 29214498
TI  - Cloning and Aggregation Characterization of Rubber Elongation Factor and Small
      Rubber Particle Protein from Ficus carica.
AB  - Rubber elongation factor (REF) and small rubber particle protein (SRPP) are major
      latex proteins harvested from Hevea brasiliensis (the rubber tree; HbREF and
      HbSRPP, respectively). Their amino acid sequences exhibit high homology with each
      other. In the present study, we cloned two cDNAs encoding REF/SRPP-family
      proteins (FcREF/SRPP-1 and -2) from the laticifers of Ficus carica (fig tree).
      The amino acid sequences of these proteins showed high homology not only with
      each other but also with HbREF and HbSRPP. Recombinant FcREF/SRPP-1 and -2 were
      expressed in E. coli, and their aggregation properties were examined using a
      Congo red binding assay, agarose gel electrophoresis, and transmission electron
      microscopy. FcREF/SRPP-1 formed fibrils when incubated in PBS, and grew to
      micrometer-sized amorphous aggregates that precipitated rapidly. These
      aggregation properties of FcREF/SRPP-1 are quite similar to those of HbREF,
      although the growth rate and size of FcREF/SRPP-1 aggregates were inferior to
      those of HbREF. FcREF/SRPP-2 also formed aggregates during the incubation, but
      they did not precipitate, as has been reported for HbSRPP. Our results suggest
      that FcREF/SRPP-1 and -2 correspond to HbREF and HbSRPP, respectively. These
      aggregation properties could provide useful benchmarks for classifying REF/SRPP
      family proteins as REF or SRPP.

PMID- 29214500
TI  - Enhancing Cellulase and Hemicellulase Production in Trichoderma orientalis EU7-22
      via Knockout of the creA.
AB  - The role of the transcription factor creA-mediating carbon catabolite repression
      in Trichoderma orientalis EU7-22 was investigated for cellulase and hemicellulase
      production. The binary vector pUR5750G/creA::hph was constructed to knock out
      creA by homologous integration, generating the DeltacreA mutant Trichoderma
      orientalis CF1D. For strain CF1D, the filter paper activities (FPA),
      endoglucanase activities (CMC), cellobiohydrolase activity(CBH), beta-glucosidase
      activity (BG), xylanase activity (XYN), and extracellular protein concentration
      were 1.45-, 1.15-, 1.71-, 2.51-, 2.72, and 1.95-fold higher in inducing medium
      and were 6.41-, 7.50-, 10.27-, 11.79-, 9.25-, and 3.77-fold higher in glucose
      repressing medium, respectively, than those in the parent strain after 4 days.
      SDS-PAGE demonstrated that the extracellular proteins were largely secreted in
      the mutant CF1D. Quantitative reverse-transcription polymerase chain reaction
      indicated that the expressions of cbh1, cbh2, eg1, eg2, bgl1, xyn1, and xyn2 were
      significantly increasing for the mutant CF1D not only in the inducing medium but
      also in the repressing medium. Those results indicated that creA was a valid
      target gene in strain engineering for improved enzyme production in T.
      orientalis.

PMID- 29214499
TI  - Microbial Degradation of Forensic Samples of Biological Origin: Potential Threat
      to Human DNA Typing.
AB  - Forensic biology is a sub-discipline of biological science with an amalgam of
      other branches of science used in the criminal justice system. Any nucleated
      cell/tissue harbouring DNA, either live or dead, can be used as forensic
      exhibits, a source of investigation through DNA typing. These biological
      materials of human origin are rich source of proteins, carbohydrates, lipids,
      trace elements as well as water and, thus, provide a virtuous milieu for the
      growth of microbes. The obstinate microbial growth augments the degradation
      process and is amplified with the passage of time and improper storage of the
      biological materials. Degradation of these biological materials carriages a huge
      challenge in the downstream processes of forensic DNA typing technique, such as
      short tandem repeats (STR) DNA typing. Microbial degradation yields improper or
      no PCR amplification, heterozygous peak imbalance, DNA contamination from non
      human sources, degradation of DNA by microbial by-products, etc. Consequently,
      the most precise STR DNA typing technique is nullified and definite opinion can
      be hardly given with degraded forensic exhibits. Thus, suitable precautionary
      measures should be taken for proper storage and processing of the biological
      exhibits to minimize their decaying process by micro-organisms.

PMID- 29214501
TI  - Mouse embryonic fibroblast (MEF)/BMP4-conditioned medium enhanced multipotency of
      human dental pulp cells.
AB  - Dental pulp cells (DPCs) are valuable cell source for dental regeneration, albeit
      their application is restricted by limited pluripotency due to current culture
      condition. Mouse embryonic fibroblasts (MEFs) are served as feeder layer to
      maintain undifferentiated state of iPSCs and ESCs with long-term in vitro
      culture. Bone morphogenetic protein 4 (BMP4) plays an important role in the
      regulation of undifferentiated state and lineage commitment of cells through
      modulation of microenvironment. However, so far little was known how micro
      environment affect the multipotency of dental derived cells. To demonstrate the
      effect of optimized culture condition on multipotency of DPCs, cell proliferation
      and senescence of DPCs with MEF and/or rhBMP4-CM were examined by CCK8,
      telomerase activity and flow cytometry. Multilineage differentiation was detected
      by immunofluorescent staining, Real-time PCR and western blot. Expression of
      BMP4/NFATc1/LIF in the co-culture medium was evaluated by ELISA and expression of
      Oct-4/Sox2/c-Myc/NFATc1 in co-cultured DPCs was detected by Real-time PCR. NFATc1
      inhibitor INCA-6 was applied to DPCs with MEF and/or rhBMP4-CM, expression of
      NFATc1/Oct-4/Sox2/c-Myc was examined by Realtime PCR and western blot. Our
      results demonstrated that DPCs cultured with MEF and/or rhBMP4-CM showed
      increased cell proliferation, telomerase rate and multilineage differentiation
      capability. MEF-CM enhanced expression of Oct-4/Sox2/c-Myc/NFATc1 in co-cultured
      DPCs through secretion of BMP4/NFATc1 in the culture medium. INCA-6 effectively
      restrained the MEF/BMP4-CM induced upregulation of Oct-4/Sox2/c-Myc/NFATc1 in
      DPCs. These resuts indicate that both MEF-CM and BMP4-CM provided similar
      efficient culture system to improve the multipotency of DPCs, which might
      contribute to the application of DPCs in dental regeneration.

PMID- 29214502
TI  - Highly Efficient Inverted Perovskite Solar Cells with CdSe QDs/LiF Electron
      Transporting Layer.
AB  - Organic/inorganic hybrid perovskite solar cell has emerged as a very promising
      candidate for the next generation of near-commercial photovoltaic devices. Here
      in this work, we focus on the inverted perovskite solar cells and have found that
      remarkable photovoltaic performance could be obtained when using cadmium selenide
      (CdSe) quantum dots (QDs) as electron transporting layer (ETL) and lithium
      fluoride (LiF) as the buffer, with respect to the traditionally applied and high
      cost [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). The easily processed and
      low-cost CdSe QDs/LiF double layer could facilitate convenient electron-transfer
      and collection at the perovskite/cathode interface, promoting an optoelectric
      conversion efficiency of as high as 15.1%, very close to that with the
      traditional PCBM ETL. Our work provides another promising choice on the ETL
      materials for the highly efficient and low-cost perovskite solar cells.

PMID- 29214503
TI  - Epidemiology and clinical characteristics of human coronaviruses OC43, 229E,
      NL63, and HKU1: a study of hospitalized children with acute respiratory tract
      infection in Guangzhou, China.
AB  - Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory
      viruses which cause various respiratory diseases, including pneumonia. There is a
      paucity of evidence on the epidemiology and clinical manifestations of these four
      HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized
      children with acute respiratory tract infection from July 2009 to June 2016 in
      Guangzhou, China. These were tested for four strains of HCoV infection using real
      time polymerase chain reaction (PCR). HCoV-positive patients were then tested for
      11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for
      HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399),
      0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7-12 months
      had the highest prevalence of HCoV and OC43 when compared with other age groups
      (p < 0.001). The peak seasons of infection varied depending on the HCoV strain.
      Patients infected with a single strain of HCoV infection were less likely to
      present fever (>= 38  degrees C) (p = 0.014) and more likely to present pulmonary
      rales (p = 0.043) than those co-infected with more than one HCoV strain or other
      respiratory pathogens. There were also significant differences in the prevalence
      of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and
      abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected.
      This retrospective study of the prevalence of four HCoV strains and clinical
      signs among a large population of pediatric patients in a subtropical region of
      China provides further insight into the epidemiology and clinical features of
      HCoV.

PMID- 29214504
TI  - Postmarketing experience with Neutrolin(r) (taurolidine, heparin, calcium
      citrate) catheter lock solution in hemodialysis patients.
AB  - Catheter-related bloodstream infections (CRBSI) are major complications for
      patients with life-threatening conditions requiring chronic vascular
      catheterization. The wide range of etiologic microbes and the ongoing development
      of resistance to antimicrobials with specific mechanisms of action make this an
      appropriate target for applying a nonspecific antimicrobial therapeutic.
      Taurolidine hydrolyzes into two antimicrobial moieties, formaldehyde and
      methylene glycol, which react with microbial surfaces. Neutrolin(r) (taurolidine,
      heparin, calcium citrate) was recently introduced in Germany as an antimicrobial
      catheter lock solution. This postmarketing experience collected data on 201
      patients at 20 centers from January 2014 through September 2016. Likely CRBSI was
      observed in 13 episodes in 47,118 days (0.2759 per 1000 days [0.1468, 0.4718]).
      Thrombosed catheter was observed in seven catheters in 47,118 days (0.1486 per
      1000 days [0.0595, 0.3061]). No adverse drug reactions that led to the
      discontinuation of Neutrolin(r) use were reported. Two patients experienced
      occasional transient dysgeusia. Neutrolin(r), when used in conjunction with
      guideline-based catheter care, showed reduction in the rate of both CRBSI and
      catheter thrombosis relative to recent historical controls.

PMID- 29214505
TI  - Efficacy and Safety of Three Cryotherapy Devices for Wart Treatment: A
      Randomized, Controlled, Investigator-Blinded, Comparative Study.
AB  - INTRODUCTION: Cutaneous warts are common skin lesions, caused by human
      papillomavirus. For years, liquid nitrogen is the cryogen of choice for wart
      treatment. Alternatively, several cryogenic devices for home treatment are
      commercially available. The present trial assessed efficacy and safety of a novel
      nitrous oxide-based cryogenic device for home use (EndWarts Freeze(r) in Europe,
      Compound W(r) Nitro-Freeze in the USA). METHODS: This investigator-blinded,
      controlled, randomized study compared the nitrous oxide device (test product)
      with a dimethylether propane-based product (Wartner(r); comparator 1). Subjects
      with common or plantar warts (50/50 ratio) were randomized into two groups (n =
      58, test product; n = 40, comparator 1). Sequentially, an extra treatment arm (n
      = 40) was added to compare with a dimethylether-based product with metal nib
      (Wortie(r); comparator 2). Main objective implied comparison of the percentage
      cured subjects after one to maximum three treatments. Efficacy and safety was
      evaluated by a blinded investigator. RESULTS: After a maximum of three
      applications, a significantly (p = 0.001) higher cure rate of 70.7% (Intention-to
      Treat analysis) was observed with test product versus 46.2% (comparator 1) and
      47.5% (comparator 2). Almost three times more subjects were cured after 1 test
      product application (29.3%), versus comparator 1 (10.4%) and comparator 2
      (12.5%). Reported side effects were transient and typical of cryotherapy. All
      treatments were well-tolerated. CONCLUSION: The superior cure rates for the test
      product versus two comparators can be explained by its design. Combination of
      nitrous oxide (cooling agent), the specific activation method (holding the liquid
      coolant in the cap), and skin-conforming polyurethane foam, results in higher
      cooling efficiency (- 80  degrees C) and more effective wart freezing. This trial
      demonstrated that the nitrous oxide device is a safe, user-friendly and effective
      wart treatment for home use, comparing favourably to dimethylether (propane)
      devices with higher freezing temperature, regardless of the applicator type.
      FUNDING: Oystershell Laboratories. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier, NCT03129373.

PMID- 29214506
TI  - Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co
      Administered with Intravenous Morphine in Healthy Adult Subjects.
AB  - BACKGROUND AND OBJECTIVE: Several features favor paracetamol (acetaminophen)
      administration by the intravenous rather than the oral route in the postoperative
      setting. This study compared the pharmacokinetics and bioavailability of oral and
      intravenous paracetamol when given with or without an opioid, morphine. METHODS:
      In this randomized, single-blind, parallel, repeat-dose study in healthy adults,
      subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at
      6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals.
      Comparisons of plasma pharmacokinetic profiles were conducted before, during, and
      after opioid co-administrations. RESULTS: Twenty-two subjects were included in
      the pharmacokinetic analysis. Observed paracetamol peak concentration (C max) and
      area under the plasma concentration-time curve over the dosing interval (AUC0-6)
      were reduced when oral paracetamol was co-administered with morphine (reduced
      from 11.6 to 7.25 ug/mL and from 31.00 to 25.51 ug.h/mL, respectively), followed
      by an abruptly increased C max and AUC0-6 upon discontinuation of morphine (to
      13.5 ug/mL and 52.38 ug.h/mL, respectively). There was also a significantly
      prolonged mean time to peak plasma concentration (T max) after the 4th dose of
      oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However,
      pharmacokinetic parameters of paracetamol were not impacted when intravenous
      paracetamol was co-administered with morphine. CONCLUSIONS: Morphine co
      administration significantly impacted the pharmacokinetics of oral but not
      intravenous paracetamol. The abrupt release of accumulated paracetamol at the end
      of morphine-mediated gastrointestinal inhibition following oral but not
      intravenous administration of paracetamol suggests that intravenous paracetamol
      provides a better option for the management of postoperative pain.
      CLINICALTRIALS. GOV IDENTIFIER: NCT02848729.

PMID- 29214507
TI  - Comparison of Once-Daily Bemiparin with Twice-Daily Enoxaparin for Acute Deep
      Vein Thrombosis: A Multicenter, Open-Label, Randomized Controlled Trial.
AB  - BACKGROUND: Individuals with deep vein thrombosis (DVT) have an increased risk of
      pulmonary embolism (PE), death, and long-term thrombotic complications.
      OBJECTIVES: To evaluate the efficacy and safety of bemiparin once daily versus
      enoxaparin twice daily in the treatment of acute DVT, and to establish
      therapeutic non-inferiority of bemiparin. PATIENTS AND METHODS: This multicenter,
      randomized, open-label, active-controlled phase III clinical trial enrolled
      patients with acute proximal DVT confirmed by complete compression ultrasound
      (CCUS). Patients received bemiparin once daily or enoxaparin twice daily
      subcutaneously for 7 days, in combination with warfarin 5 mg/day. Assessment of
      thrombotic burden was blinded and used CCUS recordings. The primary efficacy
      endpoint was the percentage of patients with an improvement in thrombotic burden
      at day 83 (end of follow-up); the secondary efficacy endpoint was the incidence
      of symptomatic recurrent DVT and PE. Safety endpoints included treatment-emergent
      adverse events. RESULTS: Three-hundred and twelve patients were enrolled (~ 62%
      male; mean age 55.2 years). At least one DVT risk factor was present in 26.1% and
      28.7% of the bemiparin and enoxaparin groups, respectively. The proportion of
      patients who had an improvement in thrombotic burden was similar for bemiparin
      (78.2%) and enoxaparin [80.8%; difference - 2.66 (97.5% CI - 12.39; infinity)],
      as was mean change in thrombus score (- 8.8 and - 8.6, respectively). There were
      no cases of recurrent DVT, and one case of non-fatal symptomatic PE in each
      treatment group. No major bleeding was reported, and there was no difference in
      the incidence of non-major bleeding. CONCLUSIONS: The efficacy of bemiparin
      administered once daily is non-inferior to that of enoxaparin administered twice
      daily with a similar safety profile. CLINICALTRIALS. GOV IDENTIFIER: NCT01880216.

PMID- 29214508
TI  - Bone histomorphometry in acromegaly patients with fragility vertebral fractures.
AB  - CONTEXT: The high risk of vertebral fractures (VFs) in acromegaly patients
      despite normal bone mineral density (BMD) is well known. The reasons for this
      paradoxical finding of skeleton fragility are poorly understood due to the
      limited data on bone histomorphometry in acromegaly. OBJECTIVE: This study aimed
      to analyze histomorphometric parameters including bone microarchitecture in
      acromegaly patients with VFs and normal BMD compared to normal subjects, and also
      to evaluate the differences between active and controlled acromegaly patients.
      PATIENTS AND METHODS: Forty-seven acromegaly patients (17 active, 30 controlled),
      median (range) age 57 years (30-88) were evaluated for bone turnover,
      morphometric VFs and BMD by dual-energy X-ray absorptiometry at lumbar spine and
      hip; 12 patients with VFs and normal BMD underwent iliac crest bone biopsy; 12
      biopsies were taken at the autopsy in healthy sex and age-matched control
      subjects. RESULTS: The histomorphometric evaluation of acromegaly fractured
      patients was compared with that of normal controls and showed significantly
      reduced median (range) levels of bone volume/tissue volume (BV/TV: 15.37% (7.93
      26.75) vs. 18.61% (11.75-27.31), p = 0.036), trabecular thickness (TbTh: 77.6 um
      (61.7-88.3) vs. 82.7 um (72.3-92.0) p = 0.045), with increased trabecular
      separation (TbSp: 536.4 um (356.2-900.6) vs. 370.3 um (377.1-546.3) p = 0.038)
      and increased cortical thickness (1268 MUm (752-2521) vs. 1065 MUm (851-1205) p =
      0.025) and porosity (11.9% (10.2-13.3) vs. 4.8% (1.6-8.8) p = 0.0008). While
      active acromegaly patients showed histomophometric features of increased bone
      turnover, patients with controlled disease presented normal bone turnover with
      significantly lower osteoblastic activity, expressed as osteoblast number (p =
      0.001), active osteoblasts and vigor (p = 0.014) in the presence of reduced
      osteocyte number (p = 0.008) compared to active disease. CONCLUSIONS: The
      apparent paradox of bone fragility in acromegaly patients with a normal BMD can
      be explained by increased cortical thickness and porosity and reduced trabecular
      thickness with increased trabecular separation. These structural and
      microarchitectural abnormalities persist in the controlled phase of acromegaly
      despite bone turnover normalization. The main determinant of bone disease after
      hormonal control is severe osteoblastic dysfunction.

PMID- 29214509
TI  - A three-dimensional stereotaxic atlas of the gray short-tailed opossum
      (Monodelphis domestica) brain.
AB  - The gray short-tailed opossum (Monodelphis domestica) is a small marsupial
      gaining recognition as a laboratory animal in biomedical research. Despite
      numerous studies on opossum neuroanatomy, a consistent and comprehensive
      neuroanatomical reference for this species is still missing. Here we present the
      first three-dimensional, multimodal atlas of the Monodelphis opossum brain. It is
      based on four complementary imaging modalities: high resolution ex vivo magnetic
      resonance images, micro-computed tomography scans of the cranium, images of the
      face of the cutting block, and series of sections stained with the Nissl method
      and for myelinated fibers. Individual imaging modalities were reconstructed into
      a three-dimensional form and then registered to the MR image by means of affine
      and deformable registration routines. Based on a superimposition of the 3D
      images, 113 anatomical structures were demarcated and the volumes of individual
      regions were measured. The stereotaxic coordinate system was defined using a set
      of cranial landmarks: interaural line, bregma, and lambda, which allows for easy
      expression of any location within the brain with respect to the skull. The atlas
      is released under the Creative Commons license and available through various
      digital atlasing web services.

PMID- 29214510
TI  - Myeloid deficiency of CCN3 exacerbates liver injury in a mouse model of
      nonalcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a condition in which fat accumulates
      in the liver of patients without a prior history of alcohol abuse. The most
      severe form, nonalcoholic steatohepatitis (NASH), often leads to hepatic fibrosis
      and cirrhosis with ensuing complications. To date, there is no pharmacologic
      treatment for NASH. The biological effects of CCN3, specifically its role in the
      regulation of inflammation, reactive oxygen species production and angiogenesis,
      have been recently established. Additional data suggests that CCN3 is associated
      with the development of tumors in the liver yet may be protective of liver
      fibrogenesis. Currently, the role of CCN3 in NAFLD/NASH remains unexplored.
      Therefore, the objective of our investigation was to decipher the role of myeloid
      deficient CCN3 in the pathogenesis of NASH and the underlying mechanisms of CCN3
      in modulation of hepatic function. Wild type and myeloid CCN3-deficient mice were
      fed a methionine- and choline-deficient diet to induced NASH. Increased lipid,
      cholesterol, and cholesterol ester accumulation was observed in myeloid CCN3
      deficient mice when compared to the control group. This disease state was
      associated with alterations of key genes involved in lipid synthesis, beta
      oxidation and lipid uptake. Additionally, the levels of important molecules
      critical for inflammation, ROS generation, ER stress and liver injury were
      significantly elevated; as was the observed severity of hepatic apoptosis and
      necroptosis. Therefore, CCN3 is critical for protection from hepatic apoptosis
      and necroptosis in our induced NASH model and our findings suggest that CCN3 can
      be exploited as a therapeutic target for the treatment of NASH.

PMID- 29214511
TI  - Managing Gout Flares in the Elderly: Practical Considerations.
AB  - Gout is common in the elderly, affecting an estimated 4.7 million people aged >
      60 years in the USA alone. The incidence and prevalence of gout increases, and
      male predisposition to gout reduces, with increasing age. The elderly have more
      comorbidities, and gout manifests differently, with more frequent involvement of
      knees, ankles, and wrists at disease onset, systemic upset, and tophi.
      Comorbidities and polypharmacy make the management of gout flares challenging in
      this population. Intra-articular corticosteroid injection remains the treatment
      of choice for accessible joints, oral prednisolone is preferred over low-dose
      colchicine, and non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided.
      Xanthine oxidase inhibitors (XOI) remain the first-line treatment for
      hyperuricemia in the elderly. Arhalofenate, an emerging uricosuric anti
      inflammatory drug, prevents gout flares while reducing serum urate. It may be
      particularly relevant in the treatment of gout in the elderly as they are unable
      to tolerate long-term colchicine for flare prophylaxis and frequently have
      contraindications to corticosteroids and NSAIDs. However, given its modest urate
      lowering effect, it can only be used in combination with an XOI, and the safety
      and efficacy of this drug has not been examined in the elderly or in those with
      chronic kidney disease. Diuretics and beta-blockers should be discontinued where
      feasible, whereas low-dose aspirin can be continued if otherwise indicated.

PMID- 29214512
TI  - Anticholinergic Prescribing in Medicare Part D Beneficiaries Residing in Nursing
      Homes: Results from a Retrospective Cross-Sectional Analysis of Medicare Data.
AB  - BACKGROUND: Prescribing of medications with anticholinergic properties in older
      nursing home residents is relatively common, despite an association with an
      increased risk for falls, delirium, and other outcomes. Few studies have
      investigated what factors influence different levels of prescribing of these
      agents. OBJECTIVES: The primary objective was to identify factors associated with
      low- and high-level anticholinergic burden in nursing home residents. A secondary
      objective was to examine in detail the contribution of different medications to
      low versus high burden to aid in determining which drugs to target in
      interventions. METHODS: This was a retrospective, cross-sectional analysis of a
      national sample of 2009-2010 Medicare Part A and B claims, Part D prescription
      drug events, and Minimum Data Set (MDS) v2.0 assessments. The cohort included
      4730 Medicare beneficiaries aged >= 65 years with continuous Medicare Parts A, B,
      and D enrollment, admitted for non-skilled stays of >= 14 days between 1 January
      2010 and 30 September 2010. Anticholinergic burden was defined using the
      Anticholinergic Cognitive Burden (ACB) scale. Medication scores were summed at
      the patient level and categorized as high (score >= 3), low (score 1-2), or none.
      Baseline predisposing factors (age, sex, race/ethnicity), enabling factors (prior
      year hospitalization, emergency department, primary care, specialist visits;
      region; Medicaid/low-income subsidy), and medical need factors (dementia
      severity, anti-dementia medication, Charlson co-morbidity index [CCI], select
      comorbidities) were evaluated for association with anticholinergic burden using
      multinomial logistic regression. RESULTS: Overall, 29.6% of subjects had a high
      anticholinergic burden and 35.2% had a low burden. High burden was most often
      (72%) due to one highly anticholinergic medication rather than a cumulative
      effect. In adjusted analyses, factors associated with increased risk of both low
      and high anticholinergic burden included comorbidity, antidementia medication,
      depression, hypertension, and prior year hospitalization. Older age was
      associated with decreased odds of high anticholinergic burden. Urinary
      incontinence and prior year specialist visit were associated with increased odds
      of high anticholinergic burden. Severe and nonsevere dementia were associated
      with decreased odds of low burden but increased odds of high burden. CONCLUSION:
      Almost two-thirds of nursing home patients have some degree of anticholinergic
      burden. Several medical need variables are significantly associated with
      increased risk for low and high anticholinergic burden. Interventions should be
      developed to optimize prescribing for residents at increased risk of receiving
      medications with anticholinergic properties. Future study is needed to evaluate
      the difference in the risk of adverse outcomes associated with various levels of
      anticholinergic burden.

PMID- 29214513
TI  - Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and
      Prefrontal Cortex in a Rat Model of Schizophrenia.
AB  - Schizophrenia is a debilitating disorder that may have a neurodevelopmental
      origin. For this reason, animal models based on neonatal insults or manipulations
      have been extensively used to demonstrate schizophrenia-related behaviors. Among
      those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model
      of schizophrenia-related behavior as it mimics behavioral and neurochemical
      abnormalities often seen in schizophrenic patients including hyperlocomotion in a
      novel environment. To investigate the neuroanatomical basis of coding novelty in
      the nVHL rat, we assessed the behavioral locomotor activity paradigm in a novel
      environment and measured expression of c-Fos, a marker of neural activation, in
      brain regions involved in the process of coding novelty or locomotion. Upon
      reaching adulthood, nVHL rats showed hyperlocomotion in the novel environment
      paradigm. Moreover, in nVHL rats the expression of c-Fos was greater in the
      prefrontal cortex (PFC) and CA1 region of the dorsal hippocampus compared to sham
      rats. Whereas similar expression of c-Fos was observed in the basolateral
      amygdala, nucleus accumbens and dentate gyrus region of  hippocampus of nVHL and
      sham rats. These results suggest that the nVHL disrupts the neural activity in
      the PFC and CA1 region of hippocampus in the process of coding novelty in the
      rat.

PMID- 29214514
TI  - Predictors of upstage diagnosis after endoscopic resection of gastric low-grade
      dysplasia.
AB  - BACKGROUND: The optimal management of precursor lesions such as gastric low-grade
      dysplasia is crucial in order to improve gastric cancer-related mortality.
      However, there are no universally accepted management guidelines regarding which
      lesions should be resected or should be monitored by follow-up visits. PATIENTS
      AND METHODS: We retrospectively analyzed data from 1006 gastric low-grade
      dysplasia lesions that had been resected via endoscopic submucosal dissection. We
      also evaluated the endoscopic risk factors associated with upstage diagnosis from
      low-grade dysplasia to high-grade dysplasia or gastric cancer. RESULTS: The mean
      age of our patients was 63.7 +/- 9.1 years and 70.3% of our study population
      included men. The predominant location and gross type of lesions was the lower
      third of the stomach (78.6%) and the elevated type (57.8%), respectively. The
      rates of pathological concordance, upstage, and downstage diagnosis were 85.3,
      12.1, and 2.6%, respectively. Multivariate analysis, after adjusting for age and
      sex, showed that a lesion size >= 10 mm (Odds ratio [OR] 2.231; p = 0.003),
      erythema (OR 7.315; p < 0.001), nodularity (OR 5.589; p < 0.001), depression (OR
      3.024; p = 0.002), and erosion (OR 7.680; p < 0.001) were all factors
      significantly associated with upstage diagnosis. Furthermore, an increasing
      number of risk factors was associated with an increasing frequency of upstage
      diagnosis; if there were no risk factors, then there was no upstage diagnosis.
      CONCLUSIONS: This study identified several risk factors that were significantly
      associated with the upstage diagnosis of gastric low-grade dysplasia: lesion size
      >= 10 mm and a variety of surface changes (erythema, nodularity, depression, and
      erosion). Our data indicate that if there is no evidence of these endoscopic risk
      factors, then regular follow-up may be considered, according to the patient's
      combined comorbid conditions.

PMID- 29214515
TI  - Robotic skills can be aided by laparoscopic training.
AB  - BACKGROUND: General Surgery is currently the fastest growing specialty with
      regards to robotic surgical system utilization. Contrary to the experience in
      laparoscopy, simulator training for robotic surgery is not widely employed partly
      because robotic surgical simulators are expensive. We sought to determine the
      effect of a robotic simulation curriculum and whether robotic surgical skills
      could be derived from those psychomotor skills attained in laparoscopic training.
      METHODS: Twenty-seven trainees with no prior robotic experience and limited
      laparoscopy exposure were randomly assigned to one of three training groups: no
      simulator training, training on a fundamentals of laparoscopic surgery (FLSTM)
      standard box trainer, and training on a robotic computer based simulator (da
      Vinci Skills SimulatorTM). Baseline robotic surgical skills were assessed on the
      clinical robot docked to a standard FLS trainer box on two tasks-intracorporeal
      knot tying and peg transfer. Subjects subsequently underwent four 1-h long
      training sessions in their assigned training environment over a course of several
      weeks. Robotic surgical skills were reassessed on the robot on the same two tasks
      used to assess skills prior to training. RESULTS: FLS training resulted in a
      greater score improvement than no training for both knot and peg scores. FLS
      training was also determined to result in greater score improvement than robotic
      simulator training for knot tying. There was no significant difference in peg
      transfer or knot tying scores when comparing robotic simulator training and no
      training. CONCLUSIONS: Robotic surgical skills can be in part derived from
      psychomotor skills developed in a laparoscopic trainer, especially for complex
      skills such as intracorporeal knot tying. Acquisition of robotic surgical skills
      may be enhanced by practice on a laparoscopic simulator using the FLS curriculum.
      This may be especially helpful when a robotic simulator is not available or is
      poorly accessible.

PMID- 29214516
TI  - Advances in stereotactic navigation for pelvic surgery.
AB  - BACKGROUND: Stereotactic navigation could improve the quality of surgery for
      rectal cancer. Critical challenges related to soft tissue stereotactic pelvic
      navigation include the potential difference in patient anatomy between
      intraoperative lithotomy and preoperative supine position for imaging. The
      objective of this study was to determine the difference in patient anatomy,
      sacral tilt, and skin fiducial position between these different patient positions
      and to investigate the feasibility and optimal set-up for stereotactic pelvic
      navigation. METHODS: Four consecutive human anatomical specimens were submitted
      to repeated CT-scans in a supine and several degrees of lithotomy position.
      Patient anatomy, sacral tilt, and skin fiducial position were compared by means
      of an image computing platform. In two specimens, a 10-degree wedge was
      introduced to reduce the natural tilt of the sacrum during the shift from supine
      to lithotomy position. A simulation of laparoscopic and transanal surgical
      procedures was performed to assess the accuracy of the stereotactic navigation.
      RESULTS: An up-to-supracentimetric change in patient anatomy was noted between
      different patient positions. This observation was minimized through the
      application of a wedge. When switching from supine to another position, sacral
      retroversion occurred independent of the use of a wedge. There was considerable
      skin fiducial motion between different positions. Accurate stereotactic
      navigation was obtained with the least registration error (1.9 mm) when the
      position of the anatomical specimen was registered in a supine position with
      straight legs, without pneumoperitoneum, using a conventional CT-scan with an
      identical specimen positioning. CONCLUSION: The change in patient anatomy is
      small during the sacral tilt induced by positional changes when using a 10-degree
      wedge, allowing for an accurate stereotactic surgical navigation. This opens up
      new promising opportunities to increase the quality of surgery for rectal cancer
      cases where it is difficult or impossible to identify and dissect along the
      anatomical planes.

PMID- 29214517
TI  - Investigating and characterizing the binding activity of the immobilized
      calmodulin to calmodulin-dependent protein kinase I binding domain with atomic
      force microscopy.
AB  - Protein-protein interactions are responsible for many biological processes, and
      the study of how proteins undergo a conformational change induced by other
      proteins in the immobilized state can help us to understand a protein's function
      and behavior, empower the current knowledge on molecular etiology of disease, as
      well as the discovery of putative protein targets of therapeutic interest. In
      this study, a bottom-up approach was utilized to fabricate micro/nanometer-scale
      protein patterns. One cysteine mutated calmodulin (CaM), as a model protein, was
      immobilized on thiol-terminated pattern surfaces. Atomic Force Microscopy (AFM)
      was then employed as a tool to investigate the interactions between CaM and CaM
      kinase I binding domain, and show that the immobilized CaM retains its activity
      to interact with its target protein. Our work demonstrate the potential of
      employing AFM to the research and assay works evolving surface-based protein
      protein interactions biosensors, bioelectronics or drug screening.

PMID- 29214518
TI  - Outcome of older persons admitted to intensive care unit, mortality, prognosis
      factors, dependency scores and ability trajectory within 1 year: a prospective
      cohort study.
AB  - BACKGROUND: The outcome and functional trajectory of older persons admitted to
      intensive care (ICU) unit remain a true question for critical care physicians and
      geriatricians, due to the heterogeneity of geriatric population, heterogeneity of
      practices and absence of guidelines. AIM: To describe the 1-year outcome,
      prognosis factors and functional trajectory for older people admitted to ICU.
      METHODS: In a prospective 1-year cohort study, all patients aged 75 years and
      over admitted to our ICU were included according to a global comprehensive
      geriatric assessment. Follow-up was conducted for 1 year survivors, in
      particular, ability scores and living conditions. RESULTS: Of 188 patients
      included [aged 82.3 +/- 4.7 years, 46% of admissions, median SAPS II 53.5 (43
      74), ADL of Katz's score 4.2 +/- 1.6, median Barthel's index 71 (55-90), AGGIR
      scale 4.5 +/- 1.5], the ICU, hospital and 1-year mortality were, respectively,
      34, 42.5 and 65.5%. Prognosis factors were: SAPS 2, mechanical ventilation,
      comorbidity (Lee's and Mc Cabe's scores), disability scores (ADL of Katz's score,
      Barthel's index and AGGIR scale), admission creatinin, hypoalbuminemia, malignant
      haemopathy, cognitive impairment. One-year survivors lived in their own home for
      83%, with a preserved physical ability, without significant variation of the
      three ability assessed scores compared to prior ICU admission. CONCLUSION: The
      mortality of older people admitted to ICU is high, with a significant impact of
      disabilty scores, and preserved 1-year survivor independency. Other studies,
      including a better comprehensive geriatric assessment, seem necessary to
      determine a predictive "phenotype" of survival with a "satisfactory" level of
      autonomy.

PMID- 29214519
TI  - Functional capacity improves in-line with neuromuscular performance after 12
      weeks of non-linear periodization strength training in the elderly.
AB  - BACKGROUND: While it is accepted that resistance training can improve functional
      capacity in older individuals, the neuromuscular source of this improvement has
      yet to be identified. AIM: This study investigated the link between improved
      neuromuscular performance and functional capacity after a 12-week resistance
      training period in untrained healthy older individuals. METHODS: Fifteen older
      men and women (60-71 years) adhered to a 4-week control period, followed by 12
      weeks of non-linear resistance training for the lower limbs. Maximum dynamic leg
      press strength (1-RM), maximum isometric knee extension torque and rate of torque
      development (RTD) were evaluated at - 4, 0, 4, 8, and 12 weeks, and muscle
      activity was assessed at 0, 4, 8, and 12 weeks. Functional capacity tests (chair
      rise, stair ascent and descent, and timed up and go) were performed at - 4, 0,
      and 12 weeks. RESULTS: No changes occurred during the control period, but the
      group increased their 1-RM strength (from 142 +/- 53 to 198 +/- 43 kg, p =
      0.001), which was accompanied by an increase in vastus lateralis activation (p =
      0.008) during the intervention. Increase was observed at all RTD time intervals
      at week 8 (p < 0.05). Significant improvements in all the functional capacity
      tests were observed at week 12 (p < 0.05). DISCUSSION: Despite the expected
      increase in strength, RTD, muscle activity, and functional capacity, there was no
      significant relationship between the changes in neuromuscular performance and
      functional capacity. While resistance training elicits various positive
      improvements in healthy older individuals, actual strength gain did not influence
      the gain in functional capacity. CONCLUSION: The present study highlights the
      exact cause that improved the functional capabilities during resistance training
      are currently unknown.

PMID- 29214520
TI  - High density SNP and DArT-based genetic linkage maps of two closely related oil
      palm populations.
AB  - Oil palm (Elaeis guineensis Jacq.) is an outbreeding perennial tree crop with
      long breeding cycles, typically 12 years. Molecular marker technologies can
      greatly improve the breeding efficiency of oil palm. This study reports the first
      use of the DArTseq platform to genotype two closely related self-pollinated oil
      palm populations, namely AA0768 and AA0769 with 48 and 58 progeny respectively.
      Genetic maps were constructed using the DArT and SNP markers generated in
      combination with anchor SSR markers. Both maps consisted of 16 major independent
      linkage groups (2n = 2* = 32) with 1399 and 1466 mapped markers for the AA0768
      and AA0769 populations, respectively, including the morphological trait "shell
      thickness" (Sh). The map lengths were 1873.7 and 1720.6 cM with an average marker
      density of 1.34 and 1.17 cM, respectively. The integrated map was 1803.1 cM long
      with 2066 mapped markers and average marker density of 0.87 cM. A total of 82% of
      the DArTseq marker sequence tags identified a single site in the published genome
      sequence, suggesting preferential targeting of gene-rich regions by DArTseq
      markers. Map integration of higher density focused around the Sh region
      identified closely linked markers to the Sh, with D.15322 marker 0.24 cM away
      from the morphological trait and 5071 bp from the transcriptional start of the
      published SHELL gene. Identification of the Sh marker demonstrates the robustness
      of using the DArTseq platform to generate high density genetic maps of oil palm
      with good genome coverage. Both genetic maps and integrated maps will be useful
      for quantitative trait loci analysis of important yield traits as well as
      potentially assisting the anchoring of genetic maps to genomic sequences.

PMID- 29214521
TI  - Photo- and Electrochemical Valorization of Carbon Dioxide Using Earth-Abundant
      Molecular Catalysts.
AB  - The dramatic increase in anthropogenic carbon dioxide emissions in recent decades
      has forced us to look for alternative carbon-neutral processes for the production
      of energy vectors and commodity chemicals. Photo- and electrochemical reduction
      of CO2 are appealing strategies for the storage of sustainable and intermittent
      energies in the form of chemical bonds of synthetic fuels and value-added
      molecules. In these approaches, carbon dioxide is converted to products such as
      CO, HCOOH and MeOH through proton-coupled electron transfer reactions. The use of
      earth-abundant elements as components of the catalytic materials is crucial for
      the large-scale applicability of this technology. This review summarizes the most
      recent advances related to this issue, with particular focus on studies where
      molecular metal complexes are used as catalysts. In addition, with the aim of
      aiding in the design of more robust and efficient non-noble metal-based
      catalysts, we discuss the lessons learned from the corresponding mechanistic
      studies.

PMID- 29214522
TI  - On the source of non-linear light absorbance in photosynthetic samples.
AB  - This study presents a mathematical model, which expresses the absorbance of a
      photosynthetic sample as a non-linear polynomial of selected reference
      absorbance. The non-linearity is explained by inhomogeneities of a product of
      pigment concentration and light path length in the sample. The quadratic term of
      the polynomial reflects the extent of inhomogeneities, and the cubic term is
      related to deviation of the product distribution from a symmetric one. The model
      was tested by measurements of suspension of unstacked tobacco thylakoid membranes
      of different chlorophyll concentrations in cuvettes of different thicknesses. The
      absorbance was calculated from the diffuse transmittance and reflectance of
      sample, illuminated by perpendicular collimated light. The evaluated quantity was
      a sensitivity defined as the relative difference between the sample absorbance
      and the reference absorbance to the reference absorbance. The non-linearity of
      sample absorbance was demonstrated by a characteristic deviation of the
      sensitivity spectrum from a constant value. The absorbance non-linearity
      decreased on an increase of the product of pigment concentration and cuvette
      thickness. The model suggests that the sieve and detour effects influence the
      absorbance in a similar way. The model may be of interest in modeling of leaf or
      canopy optics including light absorption and scattering.

PMID- 29214523
TI  - Haematopoietic Stem Cell Transplantation Arrests the Progression of
      Neurodegenerative Disease in Late-Onset Tay-Sachs Disease.
AB  - : Tay-Sachs disease is a rare metabolic disease caused by a deficiency of
      hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in
      neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher
      level of residual HexA activity. Treatment options are limited, and there are a
      few described cases who have undergone haematopoietic stem cell transplantation
      (HSCT) with variable outcome.We describe a case of a 23-year-old male patient who
      presented with a long-standing tremor since 7 years of age. He had gait ataxia, a
      speech stammer and swallowing problems. His condition had had a static course
      apart from his tremor that had been gradually deteriorating. Because of the
      deterioration in his neurological function, the patient had an uneventful,
      matched-sibling donor bone marrow transplant at the age of 15 years. Eight years
      post-HSCT, at the age of 23, he retains full donor engraftment, and his white
      cell beta-HexA of 191 nmol/mg/h is comparable to normal controls (in-assay
      control = 187). He continues to experience some intentional tremor that is
      tolerable for daily life and nonprogressive since HSCT. CONCLUSION: HSCT is a
      potential treatment option which might arrest neurodegeneration in patients with
      LOTS.

PMID- 29214524
TI  - Effect of Storage Conditions on Stability of Ophthalmological Compounded
      Cysteamine Eye Drops.
AB  - Cystinosis is a hereditary genetic disease that results in the accumulation of
      cystine crystals in the lysosomes, leading to many clinical manifestations. One
      of these manifestations is the formation of corneal cystine crystals, which can
      cause serious ocular complications. The only available drug to treat cystinosis
      is cysteamine, which breaks cystine and depletes its accumulation in the
      lysosomes. However, the oral form of cysteamine is not effective in treating
      corneal manifestations. Thus, ophthalmic solutions of cysteamine are applied.
      Because the commercial cysteamine eye drops are not available in most countries,
      hospital pharmacies are responsible for preparing "homemade" drops usually
      without a control of stability of cysteamine in different storage conditions.
      Hence, we aimed in this study to investigate the effect of different storage
      conditions on the stability of a cysteamine ophthalmic compounded solution.
      Cysteamine ophthalmic solution was prepared in the hospital pharmacy and
      sterilized using a candle filter. The preparations are then stored either in the
      freezer at -20 degrees C or in the refrigerator at +4 degrees C for up to 52
      weeks. The amount of cysteamine hydrochloride in the preparation at different
      time points was determined using capillary electrophoresis (CE). Storage of the
      cysteamine ophthalmic preparations at +4 degrees  resulted in significant loss of
      free cysteamine at all time points, from 1 to 52 weeks of storage, when compared
      with storage in the freezer (-20 degrees C). We demonstrate that cysteamine 0.5%
      compounded eye drops are easily oxidized within the first week after storage at
      +4 degrees C, rendering the preparation less effective. Storage at -20 degrees C
      is recommended to prevent this process.

PMID- 29214525
TI  - Treatment of melanoma with selected inhibitors of signaling kinases effectively
      reduces proliferation and induces expression of cell cycle inhibitors.
AB  - Cancer treatment often tends to involve direct targeting enzymes essential for
      the growth and proliferation of cancer cells. The aim of this study was the
      recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and
      mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated
      the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin
      (mTOR), everolimus (mTOR), GDC-0879 (B-RAF), and CHIR-99021 (GSK3beta) in cell
      proliferation and expression of crucial regulatory cell cycle proteins in human
      melanoma cells: WM793 (VGP) and Lu1205 (metastatic). They were used either
      individually or in various combinations. The study on the effect of signaling
      kinases inhibitors on proliferation-BrdU ELISA test after 48-72 h. Their effect
      on the expression of cell cycle regulatory proteins: cyclin D1 and D3, cyclin
      dependent kinase CDK4 and CDK6, and cell cycle inhibitors: p16, p21, and p27, was
      studied at the protein level (western blot). Treatment of melanoma cells with
      protein kinase inhibitors led to significantly decreased cell proliferation
      except the use of a GSK-3beta kinase inhibitors-CHIR-99021. The significant
      decrease in the expression of selected cyclins and cyclin-dependent kinases
      (CDKs) with parallel increase in the expression of some of cyclin-dependent
      kinases inhibitors and in consequence meaningful reduction in melanoma cell
      proliferation by the combinations of inhibitors of signaling kinases clearly
      showed the crucial role of AKT, ERK 1/2, and mTOR signal transduction in melanoma
      progression. The results unanimously indicate those pathways as an important
      target for treatment of melanoma.

PMID- 29214526
TI  - High-intensity interval training lowers blood pressure and improves apelin and
      NOx plasma levels in older treated hypertensive individuals.
AB  - Hypertension is the major risk factor for cardiovascular diseases and is one of
      the primary causes of morbidity and mortality worldwide. Apelin levels and NO
      bioavailability are impaired in older hypertensive patients. Exercise is an
      effective intervention for treating hypertension. Our purpose was to evaluate the
      effect of high-intensity interval training on blood pressure, apelin, and NOx
      plasma levels in older treated hypertensive individuals. Thirty treated
      hypertensive subjects (61.70 +/- 5.78 years, 17 males, 13 females) were randomly
      divided into 6 weeks of high-intensity interval training (n = 15) and control (n
      = 15). The exercise training was conducted for three 35-min sessions a week (1.5
      min interval at 85-90% of heart rate reserve [HRR] and 2 min active phase at 50
      55% of HRR). Assessment of plasma apelin, nitrite/nitrate (NOx), and endothelin-1
      (ET-1) was performed before and after the intervention. At the end of the study,
      apelin, and NOx plasma levels increased significantly in the high-intensity
      interval training (HIIT) group (P = 0.021, P = 0.003, respectively). Conversely,
      ET-1 plasma levels significantly decreased in the training group after the
      intervention (P = 0.015). Moreover, there was a positive correlation between the
      change of plasma apelin and change of plasma NOx (r = 0. 771, P = 0.0008). In
      addition, there was a negative correlation between the change of plasma ET-1,
      change of plasma apelin (r = - 0.595, P = 0.019), and variation of NOx (r = -
      0.572, P = 0.025). This study indicates that, by increasing of apelin and NOx
      plasma levels, HIIT may be effective in reducing blood pressure.

PMID- 29214527
TI  - Assessment of the diagnostic value of specific anti-Toxocara IgA in Slovakian
      patients suspected to have toxocarosis.
AB  - Human toxocarosis is one of the most widespread and prevalent helminthic zoonosis
      in many countries, including Slovakia. The aim was to evaluate the usefulness of
      IgA anti-Toxocara antibody detection in the serodiagnosis of toxocarosis. The
      levels of specific IgA antibodies were determined by excretory-secretory (ES)
      enzyme-linked immunosorbent assay (ELISA). The IgA seropositivity in IgG anti
      Toxocara seropositive patients (n = 52) was 32.7% and found to be highest in the
      oldest age groups (P = 0.026). The presence of IgA in suspected patients for
      toxocarosis were evaluated in respect to some characteristics of examined
      persons. Substantially higher IgA seropositivity was detected in patients with
      increased total IgE (44.8%) than in subjects with a normal level of IgE (17.4%; P
      = 0.036). No associations (P > 0.05) were found between IgA seropositivity and
      sex, level of specific IgG antibodies, avidity of IgG, eosinophilia, domicile,
      geophagia, traveling abroad, dog/cat ownership, or clinical symptoms. The IgA
      ELISA showed sensitivity of 57.1% and specificity of 100%. Mild correlations (r =
      0.302, r = 0.305, r = - 0.409) were observed between the levels of anti-Toxocara
      IgA antibodies and age, the amounts of eosinophils and IgA antibody levels, the
      amounts of eosinophils, and the values of IgG avidity, respectively. The presence
      of anti-Toxocara IgA may facilitate the diagnosis of toxocarosis and may well be
      useful for the determination of acute Toxocara infection. Moreover, this test
      should be accompanied by other immunological markers of examined patients (e.g.,
      increased total IgE, eosinophilia, and low-avidity IgG antibodies).

PMID- 29214528
TI  - Molecular identification of Leishmania spp. isolates causes cutaneous
      leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic.
AB  - Cutaneous leishmaniasis (CL) is an important public health problem in Turkey. CL
      has been most frequently seen in Sanliurfa. There is an expectation of increase
      in the population of leishmaniasis cases with the influence of Syrian refugees
      arriving in Turkey. In this study we aimed to diagnosis of CL and identifying of
      parasite from Leishmania isolates by using ITS 1 PCR RFLP. Samples were collected
      from 135 CL patients in Sanliurfa. After the specimens were inoculated in medium
      NNN, the ones which were cultures positive were cultivated in RPMI 1640 followed
      by PCR-RFLP. Genomic DNA was extracted phenol-chloroform procedure. Samples were
      examined by using ITS 1 PCR followed by RFLP analysis. Our results indicated that
      two species, L. tropica (132 samples) and L. major (3 samples), are responsible
      for cutaneous leishmaniasis in Sanliurfa. Our study is the first scientific study
      in which it is reported molecular analyses of cutaneous leishmaniasis cases
      caused by L. major in Sanliurfa in Southestern Anatolia Region. Because CL cases
      caused by L.major are detected in our study, it is considered that genotyping is
      important for diagnosis of Leishmania and following change of epidemiology.

PMID- 29214529
TI  - A rapid and reagent-free bioassay for the detection of dioxin-like compounds and
      other aryl hydrocarbon receptor (AhR) agonists using autobioluminescent yeast.
AB  - An autonomously bioluminescent Saccharomyces cerevisiae BLYAhS bioreporter was
      developed in this study for the simple and rapid detection of dioxin-like
      compounds (DLCs) and aryl hydrocarbon receptor (AhR) agonists. This recombinant
      yeast reporter was based on a synthetic bacterial luciferase reporter gene
      cassette (lux) that can produce the luciferase as well as the enzymes capable of
      self-synthesizing the requisite substrates for bioluminescent production from
      endogenous cellular metabolites. As a result, bioluminescent signal production is
      generated continuously and autonomously without cell lysis or exogenous reagent
      addition. By linking the expression of the autobioluminescent lux reporter
      cassette to AhR activation via the use of a dioxin-responsive promoter, the S.
      cerevisiae BLYAhS bioreporter emitted a bioluminescent signal in response to DLC
      exposure in a dose-responsive manner. The model dioxin, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), could be detected within 4 h with a half
      maximal effective concentration (EC50) of ~ 8.1 nM and a lower detection limit of
      500 pM. The autobioluminescent response of BLYAhS to other AhR agonists,
      including 2,3,7,8-tetrachlorodibenzofuran (TCDF), polychlorinated bisphenyl
      congener 126 (PCB-126) and 169 (PCB-169), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin
      (HxCDD), 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), benzo[a]pyrene (BaP),
      and beta-naphthoflavone (bNF), were also characterized in this study. The non
      destructive and reagent-free nature of the BLYAhS reporter assay facilitated near
      continuous, automated signal acquisition without additional hands-on effort and
      cost, providing a simple and cost-effective method for rapid DLC detection.

PMID- 29214531
TI  - In situ, accurate, surface-enhanced Raman scattering detection of cancer cell
      nucleus with synchronous location by an alkyne-labeled biomolecular probe.
AB  - A surface-enhanced Raman scattering (SERS) method for in situ detection and
      analysis of the intranuclear biomolecular information of a cell has been
      developed based on a small, biocompatible, nuclear-targeting alkyne-tagged
      deoxyribonucleic acid (DNA) probe (5-ethynyl-2'-deoxyuridine, EDU) that can
      specially accumulate in the cell nucleus during DNA replications to precisely
      locate the nuclear region without disturbance in cell biological activities and
      functions. Since the specific alkyne group shows a Raman peak in the Raman-silent
      region of cells, it is an interior label to visualize the nuclear location
      synchronously in real time when measuring the SERS spectra of a cell. Because no
      fluorescent-labeled dyes were used for locating cell nuclei, this method is
      simple, nondestructive, non- photobleaching, and valuable for the in situ
      exploration of vital physiological processes with DNA participation in cell
      organelles. Graphical abstract A universal strategy was developed to accurately
      locate the nuclear region and obtain precise molecular information of cell nuclei
      by SERS.

PMID- 29214530
TI  - Microfluidic systems for studying dynamic function of adipocytes and adipose
      tissue.
AB  - Recent breakthroughs in organ-on-a-chip and related technologies have highlighted
      the extraordinary potential for microfluidics to not only make lasting impacts in
      the understanding of biological systems but also to create new and important in
      vitro culture platforms. Adipose tissue (fat), in particular, is one that should
      be amenable to microfluidic mimics of its microenvironment. While the tissue was
      traditionally considered important only for energy storage, it is now understood
      to be an integral part of the endocrine system that secretes hormones and
      responds to various stimuli. As such, adipocyte function is central to the
      understanding of pathological conditions such as obesity, diabetes, and metabolic
      syndrome. Despite the importance of the tissue, only recently have significant
      strides been made in studying dynamic function of adipocytes or adipose tissues
      on microfluidic devices. In this critical review, we highlight new developments
      in the special class of microfluidic systems aimed at culture and interrogation
      of adipose tissue, a sub-field of microfluidics that we contend is only in its
      infancy. We close by reflecting on these studies as we forecast a promising
      future, where microfluidic technologies should be capable of mimicking the
      adipose tissue microenvironment and provide novel insights into its physiological
      roles in the normal and diseased states. Graphical abstract This critical review
      focuses on recent developments and challenges in applying microfluidic systems to
      the culture and analysis of adipocytes and adipose tissue.

PMID- 29214532
TI  - Qualitative and quantitative temporal analysis of licit and illicit drugs in
      wastewater in Australia using liquid chromatography coupled to mass spectrometry.
AB  - The combination of qualitative and quantitative bimonthly analysis of
      pharmaceuticals and illicit drugs using liquid chromatography coupled to mass
      spectrometry is presented. A liquid chromatography-quadrupole time of flight
      instrument equipped with Sequential Window Acquisition of all THeoretical
      fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in
      influent wastewater from two wastewater treatment plants in South Australia over
      a 14-month period. A total of 100 compounds were confirmed and/or detected using
      this strategy, with 61 confirmed in all samples including antidepressants
      (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine),
      illicit drugs (cocaine, methamphetamine, amphetamine, 3,4
      methylenedioxymethamphetamine (MDMA)), and known drug adulterants (lidocaine and
      tetramisole). A subset of these compounds was also included in a quantitative
      method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer.
      The use of illicit stimulants (methamphetamine) showed a clear decrease, levels
      of opioid analgesics (morphine and methadone) remained relatively stable, while
      the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and
      Alpha PVP) varied with no visible trend. This work demonstrates the value that
      high-frequency sampling combined with quantitative and qualitative analysis can
      deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South
      Australia.

PMID- 29214533
TI  - Scanning electrochemical microscopy: an analytical perspective.
AB  - Scanning electrochemical microscopy (SECM) has evolved from an electrochemical
      specialist tool to a broadly used electroanalytical surface technique, which has
      experienced exciting developments for nanoscale electrochemical studies in recent
      years. Several companies now offer commercial instruments, and SECM has been used
      in a broad range of applications. SECM research is frequently interdisciplinary,
      bridging areas ranging from electrochemistry, nanotechnology, and materials
      science to biomedical research. Although SECM is considered a modern
      electroanalytical technique, it appears that less attention is paid to so-called
      analytical figures of merit, which are essential also in electroanalytical
      chemistry. Besides instrumental developments, this review focuses on aspects such
      as reliability, repeatability, and reproducibility of SECM data. The review is
      intended to spark discussion within the community on this topic, but also to
      raise awareness of the challenges faced during the evaluation of quantitative
      SECM data.

PMID- 29214534
TI  - Development of a sandwich ELISA with potential for selective quantification of
      human lactoferrin protein nitrated through disease or environmental exposure.
AB  - Lactoferrin (LF) is an important multifunctional protein that comprises a large
      fraction of the protein mass in certain human fluids and tissues, and its
      concentration is often used to assess health and disease. LF can be nitrated by
      multiple routes, leading to changes in protein structure, and nitrated proteins
      can negatively impact physiological health via nitrosative stress. Despite an
      awareness of the detrimental effects of nitrated proteins and the importance of
      LF within the body, cost-effective methods for detecting and quantifying nitrated
      lactoferrin (NLF) are lacking. We developed a procedure to selectively quantify
      NLF using sandwich enzyme-linked immunosorbent assay (ELISA), utilizing a
      polyclonal anti-LF capture antibody paired with a monoclonal anti-nitrotyrosine
      detector antibody. The assay was applied to quantify NLF in samples of pure LF
      nitrated via two separate reactions at molar ratios of excess nitrating agent to
      the total number of tyrosine residues between 10/1 and 100/1. Tetranitromethane
      (TNM) was used as a laboratory surrogate for an environmental pathway selective
      for production of 3-nitrotyrosine, and sodium peroxynitrite (ONOO-) was used as a
      surrogate for an endogenous nitration pathway. UV-vis spectroscopy (increased
      absorbance at 350 nm) and fluorescence spectroscopy (emission decreased by > 96%)
      for each reaction indicate the production of NLF. A lower limit of NLF detection
      using the ELISA method introduced here was calculated to be 0.065 MUg mL-1, which
      will enable the detection of human-physiologically relevant concentrations of
      NLF. Our approach provides a relatively inexpensive and practical way to assess
      NLF in a variety of systems. Graphical abstract We developed a procedure to
      selectively quantify nitrated lactoferrin (NLF) protein using a sandwich enzyme
      linked immunosorbent assay (ELISA) and verified results against several
      spectroscopic techniques. Our approach provides an inexpensive and practical way
      to assess NLF in a variety of systems.

PMID- 29214535
TI  - Simultaneous determination of 41 multiclass organic pollutants in environmental
      waters by means of polyethersulfone microextraction followed by liquid
      chromatography-tandem mass spectrometry.
AB  - A new procedure using polyethersulfone (PES) microextraction followed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis was developed in this
      work for the simultaneous determination of 41 multiclass priority and emerging
      organic pollutants including herbicides, hormones, personal care products, and
      pharmaceuticals, among others, in seawater, wastewater treatment plant (WWTP)
      effluents, and estuary samples. The optimization of the analysis included two
      different chromatographic columns and different variables (polarity, fragmentor
      voltage, collision energy, and collision cell accelerator) of the mass
      spectrometer. In the case of PES extraction, ion strength of the water, pH,
      addition of EDTA, and the amount of the polymeric material were thoroughly
      investigated. The developed procedure was compared with a previously validated
      one based on a standard solid-phase extraction (SPE). In contrast to the SPE
      protocol, the PES method allowed a cost-efficient extraction of complex aqueous
      samples with lower matrix effect from 120 mL of water sample. Satisfactory and
      comparable apparent recovery values (80-119 and 70-131%) and method
      quantification limits (MQLs, 0.4-26 and 0.2-23 ng/L) were obtained for PES and
      SPE procedures, respectively, regardless of the matrix. Repeatability values
      lower than 27% were obtained. Finally, the developed methods were applied to the
      analysis of real samples from the Basque Country and irbesartan, valsartan,
      acesulfame, and sucralose were the analytes most often detected at the highest
      concentrations (51-1096 ng/L). Graphical abstract Forty-one multiclass pollutant
      determination in environmental waters by means of PES/SPE-LC-MS/MS.

PMID- 29214536
TI  - Photonic monitoring of treatment during infection and sepsis: development of new
      detection strategies and potential clinical applications.
AB  - Despite the strong decline in the infection-associated mortality since the
      development of the first antibiotics, infectious diseases are still a major cause
      of death in the world. With the rising number of antibiotic-resistant pathogens,
      the incidence of deaths caused by infections may increase strongly in the future.
      Survival rates in sepsis, which occurs when body response to infections becomes
      uncontrolled, are still very poor if an adequate therapy is not initiated
      immediately. Therefore, approaches to monitor the treatment efficacy are
      crucially needed to adapt therapeutic strategies according to the patient's
      response. An increasing number of photonic technologies are being considered for
      diagnostic purpose and monitoring of therapeutic response; however many of these
      strategies have not been introduced into clinical routine, yet. Here, we review
      photonic strategies to monitor response to treatment in patients with infectious
      disease, sepsis, and septic shock. We also include some selected approaches for
      the development of new drugs in animal models as well as new monitoring
      strategies which might be applicable to evaluate treatment response in humans in
      the future. Figure Label-free probing of blood properties using photonics.

PMID- 29214537
TI  - Branched-chain dicationic ionic liquids for fatty acid methyl ester assessment by
      gas chromatography.
AB  - Twelve bis- or dicationic ionic liquids (ILs) including eight based on
      imidazolium, a single one based on phosphonium, and three based on pyrrolidinium
      cationic units were prepared with the bis(trifluoromethyl sulfonyl) imide anion.
      The two identical cationic moieties were attached by different alkyl spacers
      having three or five carbons and differing alkyl substituents attached to the
      spacer. The SLB-IL111 column, as the most polar commercial stationary phase
      known, was included in the study for comparison. Isothermal separations of a
      rapeseed oil fatty acid methyl ester (FAME) sample were used to study and compare
      the 12 IL-based column performances and selectivities. The retention times of the
      most retained methyl esters of lignoceric (C24:0) and erucic (C22:1) acids were
      used to estimate the IL polarity. The phosphonium dicationic IL column was, by
      far, the least polar. Imidazolium-based dicationic IL columns were the most
      polar. Polarity and selectivity for the FAME separation were somewhat related.
      The separation of a 37-FAME standard mixture allowed the investigation of
      selectivity variations observed on the 12 IL-based columns under temperature
      gradients up to 230  degrees C. The remarkable selectivity of the IL-based
      columns is demonstrated by the detailed analysis of the cis/trans C18:1 isomers
      of a partially hydrogenated vegetable oil sample on 30-m columns, separations
      competing with that done following an "official method" performed on a 100-m
      column. Graphical abstract Separation of fatty acid methyl esters on a 30-m
      3m2C5(mpy)2. 2NTf2 branched-chain dicationic IL-based column. Branched chain
      dicationic ILs show great selectivity for separation of cis/trans, omega-3/omega
      6, and detailed analysis of cis/trans fats.

PMID- 29214538
TI  - Zero valent Fe-reduced graphene oxide quantum dots as a novel magnetic dispersive
      solid phase microextraction sorbent for extraction of organophosphorus pesticides
      in real water and fruit juice samples prior to analysis by gas chromatography
      mass spectrometry.
AB  - A selective and sensitive magnetic dispersive solid-phase microextraction
      (MDSPME) coupled with gas chromatography-mass spectrometry was developed for
      extraction and determination of organophosphorus pesticides (Sevin, Fenitrothion,
      Malathion, Parathion, and Diazinon) in fruit juice and real water samples. Zero
      valent Fe-reduced graphene oxide quantum dots (rGOQDs@ Fe) as a new and effective
      sorbent were prepared and applied for extraction of organophosphorus pesticides
      using MDSPME method. In order to study the performance of this new sorbent, the
      ability of rGOQDs@ Fe was compared with graphene oxide and magnetic graphene
      oxide nanocomposite by recovery experiments of the organophosphorus pesticides.
      Several affecting parameters in the microextraction procedure, including pH of
      donor phase, donor phase volume, stirring rate, extraction time, and desorption
      conditions such as the type and volume of solvents and desorption time were
      thoroughly investigated and optimized. Under the optimal conditions, the method
      showed a wide linear dynamic range with R-square between 0.9959 and 0.9991. The
      limit of detections, the intraday and interday relative standard deviations (n =
      5) were less than 0.07 ngmL-1, 4.7, and 8.6%, respectively. The method was
      successfully applied for extraction and determination of organophosphorus
      pesticides in real water samples (well, river and tap water) and fruit juice
      samples (apple and grape juice). The obtained relative recoveries were in the
      range of 82.9%-113.2% with RSD percentages of less than 5.8% for all the real
      samples.

PMID- 29214539
TI  - Analytical method for the evaluation of the outdoor air contamination by emerging
      pollutants using tree leaves as bioindicators.
AB  - In this work, an analytical method, based on sonication-assisted extraction,
      clean-up by dispersive solid-phase extraction and determination by liquid
      chromatography-tandem mass spectrometry, has been developed and validated for the
      simultaneous determination of 15 emerging pollutants in leaves from four
      ornamental tree species. Target compounds include perfluorinated organic
      compounds, plasticizers, surfactants, brominated flame retardant, and
      preservatives. The method was optimized using Box-Behnken statistical
      experimental design with response surface methodology and validated in terms of
      recovery, accuracy, precision, and method detection and quantification limits.
      Quantification of target compounds was carried out using matrix-matched
      calibration curves. The highest recoveries were achieved for the perfluorinated
      organic compounds (mean values up to 87%) and preservatives (up to 88%). The
      lowest recoveries were achieved for plasticizers (51%) and brominated flame
      retardant (63%). Method detection and quantification limits were in the ranges
      0.01-0.09 ng/g dry matter (dm) and 0.02-0.30 ng/g dm, respectively, for most of
      the target compounds. The method was successfully applied to the determination of
      the target compounds on leaves from four tree species used as urban ornamental
      trees (Citrus aurantium, Celtis australis, Platanus hispanica, and Jacaranda
      mimosifolia). Graphical abstract Analytical method for the biomonitorization of
      emerging pollutants in outdoor air.

PMID- 29214540
TI  - Preparation of polysaccharide-based chiral stationary phases on SiO2@Ag core
      shell particles by means of coating and intermolecular polycondensation and
      comparative liquid chromatography enantioseparations.
AB  - Material with a core-shell structure based on a porous silica core and Ag
      nanoparticles (AgNPs) as shell (SiO2@Ag) was prepared with the seed growth
      method. Cellulose derivatives as chiral selectors were coated on the surfaces of
      SiO2@Ag particles by means of coating and intermolecular polycondensation as
      chiral stationary phases (CSPs), respectively. Fifteen racemates were used to
      evaluate their chiral recognition ability by high-performance liquid
      chromatography (HPLC). The results implied that the CSPs based on SiO2@Ag
      particles obtained stronger interaction with the analytes leading to better
      enantioseparation due to the existence of AgNPs on the surfaces of silica gel,
      compared with a cellulose derivative-modified silica column. In addition, the new
      CSPs showed special selectivity for ketone enantiomers, and AgNPs played a
      synergistic effect with cellulose derivatives on enantioseparation. Graphical
      abstract Schematic of SiO2@Ag stationary phase.

PMID- 29214541
TI  - New ionization tags based on the structure of the 5-azoniaspiro[4.4]nonyl tag for
      a sensitive peptide sequencing by mass spectrometry.
AB  - Quaternary ammonium salts (QAS), both linear and bicyclic, are often utilized to
      improve the mass spectrometry (MS) analysis of peptides by fixing a permanent
      positive charge on the analyzed molecule. However, during collision-induced
      dissociation (CID) experiments, QAS undergo unwanted side reactions-Hofmann
      elimination as well as a tertiary amine loss- rendering the data interpretation
      complicated. In this work, we present 2-thia- and 2-oxa-5-azoniaspiro[4.4]nonyl
      groups as heterocyclic derivatives of the highly stable ionization group, 5
      azoniaspiro[4.4]nonyl, for a sensitive peptide analysis by MS. Due to the
      permanent positive charge, labeled peptides are characterized by enhanced
      ionization efficiency during electrospray mass spectrometry (ESI-MS) conditions.
      Moreover, interpretation of the CID fragmentation of labeled peptides is
      facilitated since a series of generated fragmentation ions enable a complete
      sequence coverage. Introduction of a heteroatom into the 5-azoniaspiro[4.4]nonyl
      scaffold allows for liberation of a stable reporter ion which could be used in
      selected reaction monitoring (SRM)-targeted quantification experiments.
      Additionally, we synthesized a deuterated analog of the tag for LC-SRM-targeted
      quantitative analysis. The obtained results indicate the general usefulness of
      the proposed heterocyclic quaternary ammonium ionization tag for sequencing and
      quantification of peptides. Graphical abstract New reagents based on the
      structure of the 5-azoniaspiro[4.4]nonyl tag for peptide analysis by tandem mass
      spectrometry.

PMID- 29214542
TI  - Uncertainty evaluation in normalization of isotope delta measurement results
      against international reference materials.
AB  - Isotope delta measurements are normalized against international reference
      standards. Although multi-point normalization is becoming a standard practice,
      the existing uncertainty evaluation practices are either undocumented or are
      incomplete. For multi-point normalization, we present errors-in-variables
      regression models for explicit accounting of the measurement uncertainty of the
      international standards along with the uncertainty that is attributed to their
      assigned values. This manuscript presents framework to account for the
      uncertainty that arises due to a small number of replicate measurements and
      discusses multi-laboratory data reduction while accounting for inevitable
      correlations between the laboratories due to the use of identical reference
      materials for calibration. Both frequentist and Bayesian methods of uncertainty
      analysis are discussed.

PMID- 29214544
TI  - A New Species of Dichelacera (Dichelacera) Macquart (Diptera, Tabanidae) from the
      Brazilian Savannah.
AB  - A new species of Dichelacera (Tabanidae, Diptera) is described, based on females
      from Arraias, state of Tocantins, Brazil. Diagnosis, discussion, and
      illustrations of external and internal characters are provided. In addition, we
      provide unpublished photographs of Dichelacera callosa Lutz for comparison.

PMID- 29214543
TI  - Comparison of biological and alloplastic meshes in ventral incisional hernia
      repair.
AB  - PURPOSE: The aim of our retrospective analysis was to compare the results of
      incisional hernia repair by porcine small intestinal submucosa-derived (SIS)
      meshes with those obtained by alloplastic polypropylene-based (PP) meshes in
      comparable surgical indications by matched-pair design. We hypothesized that in
      incisional hernia, SIS mesh repair is associated with fewer recurrences and SSO
      than PP mesh repair in incisional hernias. METHODS: Twenty-four matched pairs
      (SIS vs. PP mesh repair between 1 January 2005 and 31 December 2013) were
      identified by matching criteria: gender, age, comorbidities, body mass index, EHS
      hernia classification, mesh implantation technique, CDC wound classification, and
      source of contamination/primary surgery leading to incisional hernia. Minimal
      follow-up time was 24 months. Means and standard deviations were compared by
      paired t test; categorial data were compared by McNemar's test. Poisson's
      distribution and negative binominal distribution were employed to detect
      significant correlation. RESULTS: There were no statistically significant
      differences between both groups in the pre- and perioperative factors and the
      follow-up times. There were significantly more wound complications (19 vs. 12, p
      = 0.041), longer hospital stay (22.0 +/- 6.3 vs. 12.0 +/- 3.1 days, p = 0.010),
      and significantly more recurrent hernias (25 vs. 12.5%, p = 0.004) after SIS mesh
      repair. Both the Poisson's distribution and the negative binominal distribution
      unveiled significantly more complication points (3-6 vs. 1-2) per month after SIS
      mesh repair. CONCLUSION: There is no advantage of SIS meshes compared to PP
      meshes in incisional hernia repair with different degrees of wound contamination
      in this matched-pair analysis. Further prospective and randomized trials or at
      least registry studies such as the EHS register with standardized and defined
      conditions are warranted.

PMID- 29214545
TI  - Daily Activity Patterns and Thermal Tolerance of Three Sympatric Dung Beetle
      Species (Scarabaeidae: Scarabaeinae: Eucraniini) from the Monte Desert,
      Argentina.
AB  - Tolerance to extreme temperatures, thermal limits, and the mechanisms of
      thermoregulation are related to internal functions of insects and partly define
      their ecological niche. We study the association between daily activity of dung
      beetles from the Monte Desert in Argentina and their tolerance to high
      temperatures. Results indicate that for all three sympatric species studied,
      Eucranium belenae Ocampo, Anomiopsoides cavifrons (Burmeister), and Anomiopsoides
      fedemariai Ocampo, daily activity is associated to ground temperature. Eucranium
      belenae is active when ground temperature is relatively low and it is less
      tolerant to long periods of activity at high temperatures in the lab, while A.
      cavifrons and A. fedemariai are active when ground temperatures are higher, and
      they tolerate high temperatures for longer periods of time than E. belenae in the
      lab. These species coexist and use similar food sources, and this eco
      physiological study may help to explain how they differentiate under the same
      environmental conditions. The Monte Desert is considered an extreme environment,
      and studies on thermal tolerance offer testable predictions to understand how
      species would respond to climate change.

PMID- 29214546
TI  - Biology of a Neotropical Harlequin Stink Bug, Runibia perspicua (F.).
AB  - Laboratory and field studies were conducted with nymphs and adults of the
      Neotropical stink bug Runibia perspicua (F.) to evaluate their biology on plants.
      Total nymph mortality was ca. 13% on immature fruits of Brunfelsia australis
      Benth. (IFBA) and 90% on raw shelled peanuts, Arachis hypogaea L. (RSP); no
      nymphs survived on immature pods of green bean, Phaseolus vulgaris L., or on
      immature fruits of privet, Ligustrum lucidum Ait. Nymph developmental time was
      ca. 36 on IFBA and 55 days on RSP. Body weight was significantly greater when
      nymphs were raised isolated compared to those raised in groups. Adult feeding
      activity was greater than third instars on IFBA. Adult longevity on IFBA + cherry
      tomato, Solanum lycopersicum L. fruit, reached ca. 150 days. On IFBA, fecundity
      was 2.5 egg masses/female and 48.3 eggs/female; 25.6% of the eggs hatched. Adults
      did not reproduce on tomato. Body weight gain did not increase significantly for
      both sexes during the first four weeks of adult life on IFBA. In the field,
      plants of B. australis were surveyed in Passo Fundo, RS (28 degrees 15'S; 52
      degrees 24'W). The majority of egg masses were deposited on the lower (abaxial)
      surface of leaves. Nymphs aggregated on immature fruits, and adults were seldom
      found on the plants. These are the first data on the performance of R. perspicua
      on B. australis indicating that this plant species is suitable to the bug's
      biology.

PMID- 29214547
TI  - Association of NLRP3 polymorphisms with susceptibility to primary gouty arthritis
      in a Chinese Han population.
AB  - The NLRP3-interleukin1beta (IL1beta) signaling pathway is involved in monosodium
      urate (MSU)-mediated inflammation. The aim of this present study was to determine
      whether single nucleotide polymorphisms (SNPs) in the NLRP3 gene are associated
      with susceptibility to gouty arthritis (GA) and whether these SNPs alter the
      expression of components of the NLRP3-IL1beta signaling pathway. The rs10754558,
      rs4612666, and rs1539019 SNPs were detected in 583 patients with GA and 459
      healthy subjects. NLRP3 and IL1beta mRNA levels in peripheral blood mononuclear
      cells (PBMCs) and serum IL1beta levels were measured in different genotype
      carriers, and correlations between the NLRP3 SNPs and NLRP3 mRNA, IL1beta mRNA,
      and serum IL1beta levels were investigated. The GG genotype of NLRP3 rs10754558
      was found to be significantly associated with patients with GA compared to the
      healthy control subjects via multivariate logistic regression analysis (adjusted
      OR = 2.68, P = 0.006). The CGA haplotypes were independently associated with
      patients with GA compared to the healthy control subjects (adjusted OR = 1.968, P
      = 0.02). The levels of NLRP3 mRNA, IL1beta mRNA, and serum IL1beta in the
      patients with GA were significantly different among the three genotypes of
      rs10754558 (all P < 0.01). The GG genotype of rs10754558 and the CGA haplotype of
      rs4612666-C, rs10754558-G, and rs1539019-A are both independent risk factors for
      primary GA development. The rs10754558 polymorphism might participate in
      regulating immune and inflammation responses in patients with GA by influencing
      the expression of components of the NLRP3 inflammasome. Future multicenter
      studies aimed at replicating these findings in an independent population as well
      as functional tests will aid in further defining the role of these SNPs in the
      development of GA.

PMID- 29214549
TI  - Synthesis, structure and toxicity evaluation of ethanolamine
      nitro/chloronitrobenzoates: a combined experimental and theoretical study.
AB  - BACKGROUND: Nitroaromatic and chloronitroaromatic compounds have been a subject
      of great interest in industry and recently in medical-pharmaceutic field. 2
      Chloro-4-nitro/2-chloro-5-nitrobenzoic acids and 4-nitrobenzoic acid are
      promising new agents for the treatment of main infectious killing diseases in the
      world: immunodeficiency diseases and tuberculosis. RESULTS: New ethanolamine
      nitro/chloronitrobenzoates were synthesized and characterized by X-ray
      crystallography, UV-vis, FT-IR and elementary analysis techniques. The toxicity
      of the compounds prepared and correspondent components was evaluated using
      Hydractinia echinata as test system. A significant lower toxicity was observed
      for nitro-derivative compared with chloronitro-derivatives and individual
      components. Crystallographic studies, together with the chemical reactivity and
      stability profiles resulted from density functional theory and ab initio
      molecular orbital calculations, explain the particular behavior of ethanolamine 4
      nitrobenzoate in biological test. CONCLUSIONS: The experimental and theoretical
      data reveal the potential of these compounds to contribute to the design of new
      active pharmaceutical ingredients with lower toxicity.

PMID- 29214550
TI  - The Wally plot approach to assess the calibration of clinical prediction models.
AB  - A prediction model is calibrated if, roughly, for any percentage x we can expect
      that x subjects out of 100 experience the event among all subjects that have a
      predicted risk of x%. Typically, the calibration assumption is assessed
      graphically but in practice it is often challenging to judge whether a
      "disappointing" calibration plot is the consequence of a departure from the
      calibration assumption, or alternatively just "bad luck" due to sampling
      variability. We propose a graphical approach which enables the visualization of
      how much a calibration plot agrees with the calibration assumption to address
      this issue. The approach is mainly based on the idea of generating new plots
      which mimic the available data under the calibration assumption. The method
      handles the common non-trivial situations in which the data contain censored
      observations and occurrences of competing events. This is done by building on
      ideas from constrained non-parametric maximum likelihood estimation methods. Two
      examples from large cohort data illustrate our proposal. The 'wally' R package is
      provided to make the methodology easily usable.

PMID- 29214548
TI  - First clinical symptom as a prognostic factor in systemic sclerosis: results of a
      retrospective nationwide cohort study.
AB  - The objective of the study is to determine the importance of the mode of onset as
      prognostic factor in systemic sclerosis (SSc). Data were collected from the
      Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter
      database created in 2006. As first symptom, we included Raynaud's phenomenon
      (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung
      disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility.
      A total of 1625 patients were recruited. One thousand three hundred forty-two
      patients (83%) presented with RP as first symptom and 283 patients (17%) did not.
      Survival from first symptom in those patients with RP mode of onset was higher at
      any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5
      years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years
      (p < 0.001). In multivariate analysis, factors related to mortality were older
      age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis
      (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon,
      especially in the form of puffy hands or pulmonary involvement. The mode of onset
      should be considered an independent prognostic factor in systemic sclerosis and,
      in particular, patients who initially present with non-Raynaud's phenomenon may
      be considered of poor prognosis.

PMID- 29214551
TI  - Keeping it together: Semantic coherence stabilizes phonological sequences in
      short-term memory.
AB  - Our ability to hold a sequence of speech sounds in mind, in the correct
      configuration, supports many aspects of communication, but the contribution of
      conceptual information to this basic phonological capacity remains controversial.
      Previous research has shown modest and inconsistent benefits of meaning on
      phonological stability in short-term memory, but these studies were based on sets
      of unrelated words. Using a novel design, we examined the immediate recall of
      sentence-like sequences with coherent meaning, alongside both standard word lists
      and mixed lists containing words and nonwords. We found, and replicated,
      substantial effects of coherent meaning on phoneme-level accuracy: The phonemes
      of both words and nonwords within conceptually coherent sequences were more
      likely to be produced together and in the correct order. Since nonwords do not
      exist as items in long-term memory, the semantic enhancement of phoneme-level
      recall for both item types cannot be explained by a lexically based item
      reconstruction process employed at the point of retrieval ("redintegration").
      Instead, our data show, for naturalistic input, that when meaning emerges from
      the combination of words, the phonological traces that support language are
      reinforced by a semantic-binding process that has been largely overlooked by past
      short-term memory research.

PMID- 29214552
TI  - Decomposing item-method directed forgetting of emotional pictures: Equivalent
      costs and no benefits.
AB  - Using an item-method directed forgetting task, we presented negative, neutral,
      and positive photographic pictures, one at a time, each followed by an
      instruction to remember or forget. We determined that the directed forgetting
      effect, defined as better subsequent recognition of to-be-remembered (TBR) items
      than to-be-forgotten (TBF) items, was equivalent across negative, neutral, and
      positive pictures. To disentangle the underlying costs (i.e., decrease in memory
      for TBF items) and benefits (i.e., increase in memory for TBR items), we compared
      recognition memory performance in the directed forgetting task to that of a novel
      within-subjects remember-all control condition (Experiment 1) and to a between
      subjects remember-all control group (Experiment 2). We observed costs without
      benefits across all three emotions-negative, neutral, and positive-in both
      experiments. These results demonstrate that equivalent directed forgetting
      effects for emotional stimuli are not attributable to different underlying
      component processes. Instead, our results suggest that selection for encoding is
      accomplished in similar ways, regardless of emotional content.

PMID- 29214553
TI  - Mora or more? The phonological unit of Japanese word production in the Stroop
      color naming task.
AB  - In English, Dutch, and other European languages, it is well established that the
      fundamental phonological unit in word production is the phoneme; in contrast,
      recent studies have shown that in Chinese it is the (atonal) syllable and in
      Japanese the mora. The present study investigated whether this cross-language
      variation in the size of the unit of word production is due to the type of script
      used in the language (i.e., alphabetic, morphosyllabic, or moraic). Capitalizing
      on the multiscriptal nature of Japanese, and using the Stroop color naming task,
      we show that the overlap in the initial mora between the color name and the
      written distractor facilitates color naming independent of script type. These
      results confirm the mora as the phonological unit of word production in Japanese,
      and establish the Stroop color naming task as a useful task for investigating the
      fundamental (or "proximate") phonological unit used in speech production.

PMID- 29214555
TI  - How to respond to resistiveness towards assistive technologies among persons with
      dementia.
AB  - It is a common experience among care professionals that persons with dementia
      often say 'no' to conventional caring measures such as taking medication, eating
      or having a shower. This tendency to say 'no' may also concern the use of
      assistive technologies such as fall detectors, mobile safety alarms, Internet for
      social contact and robots. This paper provides practical recommendations for care
      professionals in home health care and social care about how to respond to such
      resistiveness towards assistive technologies. Apart from the option of accepting
      the 'no', it discusses a number of methods for influencing persons with dementia
      in order to overcome the 'no'. These methods range from various non-coercive
      measures-including nudging-to coercion. It is argued that while conventional
      caring measures like those mentioned are essential for survival, health or
      hygiene, assistive technologies are commonly merely potentially beneficial
      supplements. With this in mind, it is concluded that care professionals should be
      more restrictive in using methods of influence involving some degree of pressure
      regarding assistive technologies than regarding conventional caring measures.

PMID- 29214554
TI  - Geniposide Suppresses Interleukin-1beta-Induced Inflammation and Apoptosis in Rat
      Chondrocytes via the PI3K/Akt/NF-kappaB Signaling Pathway.
AB  - Osteoarthritis (OA) is a chronic degenerative joint disease that is principally
      characterized by progressive joint dysfunction and cartilage degradation.
      Inflammation and apoptosis play critical roles in the progression of OA.
      Geniposide (GPO), one of the principal components of the fruit of Gardenia
      jasminoides Ellis, has been reported to have anti-inflammatory and other
      pharmacological effects. In this study, we performed in vitro experiments on rat
      chondrocytes to examine the therapeutic effects of GPO on OA and investigated its
      effects in vivo in a rat model of OA induced by medial meniscal tear (MMT). The
      results suggest that GPO can inhibit the expression of INOS, COX-2, and MMP-13 in
      vitro, and promote the expression of collagen II in rat chondrocytes stimulated
      with interleukin-1beta (IL-1beta). In addition, we also found that GPO can
      inhibit the expression of pro-apoptotic proteins such as Bax, Cyto-c, and C
      caspase3 and increase the expression of the anti-apoptotic protein Bcl-2. These
      changes may be related to GPO-induced inhibition of the IL-1beta-induced
      activation of the PI3K/Akt/NF-kappaB signaling pathway. In vivo, we also found
      that GPO can limit the development of OA in a rat model. Taken together, the
      above results indicate that GPO has potential therapeutic value for treating OA.

PMID- 29214556
TI  - Influence of genetic modifiers on sudden cardiac death cases.
AB  - Sequence variants in the ion channel genes KCNH2 and SCN5A may cause the cardiac
      disorder long QT syndrome (LQTS). This disorder is associated with incomplete
      penetrance and variable expression in KCNH2- or SCN5A-mutation carriers. Common
      genetic variants, if associated with a mutation, may affect the severity of this
      cardiac disorder. This study identified rare mutations in the cardiac ion channel
      genes KCNH2 and SCN5A in a SCD case, as well as in a LQTS-affected family with a
      history of SCD. Moreover, common variants were found to occur together within the
      same genes. These findings support the concept that common single-nucleotide
      polymorphisms (SNPs) in genes encoding cardiac ion channels can directly modulate
      the functional effect of mutations and therefore enhance or weaken the risk of
      cardiac events.

PMID- 29214557
TI  - Laparoscopic intraperitoneal onlay mesh for pediatric incisional hernia-a case
      report.
AB  - BACKGROUND: The incidence of incisional hernia in pediatric patients is low in
      comparison with that reported in adults. In the pediatric population, primary
      closure has generally been favored. However, synthetic or biomedical mesh offers
      advantages in the repair of larger defects when primary closure is difficult. The
      use of laparoscopic intraperitoneal onlay mesh (IPOM) in the adult population has
      been well documented. In the pediatric population, a few laparoscopic approaches
      with direct suturing have been proposed; however, there are no reports of
      laparoscopic repair with the use of IPOM. CASE PRESENTATION: The patient was a 1
      year-old girl with epigastric incisional hernia after an operation to correct a
      complete arteriovenous septal defect. The fascial defect (size 30 * 35 mm) was
      large; thus, direct suturing was considered to be associated with a high risk of
      thoracic deformation and recurrence. Laparoscopic IPOM was performed. The fascial
      defect was detected precisely through the laparoscopy, and non-absorbable mesh
      was placed through a 12-mm trocar. Minimal incisions were required for the
      trocars, and extensive dissection of the abdominal wall structure was not needed.
      This procedure allowed for the integrity and functional status of the abdominal
      wall to be maintained. CONCLUSION: Laparoscopic IPOM is a minimally invasive and
      cosmetically acceptable method that can be applied to the treatment of large
      incisional hernias in children.

PMID- 29214558
TI  - Hepatitis E Seroprevalence and Genotyping in a Cohort of Wild Boars in Southern
      Germany and Eastern Alsace.
AB  - In the last few years it has been realized that the hepatitis E virus (HEV) is
      endemic in most industrialized countries and that it is a zoonotic disease.
      Potential reservoirs for HEV have been identified to be wild boars and deers, but
      HEV has also been found in domestic pigs and other animals. Due to the probable
      spread of the virus via contaminated food or contact to infected animals, HEV
      antibodies are present in more than 16% of the German adult population and rates
      are increasing with age. We collected blood from 104 wild boars in southern
      Germany and the border region of Alsace. We found an anti-HEV seroprevalence of
      11.5% in our cohort, using ELISA. Furthermore, we observed active infection in
      3.85% of the animals by positive HEV PCR in the sera of the boars. In our cohort,
      no regional differences of seroprevalence or active infection were seen.
      Sequencing revealed rather close homology of some detected HEV sequences to
      genotypes isolated from patients in Germany. Hence wild boars are a potential
      source of HEV infection in Middle Europe and the rate of infectious animals is
      quite high.

PMID- 29214559
TI  - Virus Type-Specific Removal in a Full-Scale Membrane Bioreactor Treatment
      Process.
AB  - We investigated removal of noroviruses, sapoviruses, and rotaviruses in a full
      scale membrane bioreactor (MBR) plant by monitoring virus concentrations in
      wastewater samples during two gastroenteritis seasons and evaluating the
      adsorption of viruses to mixed liquor suspended solids (MLSS). Sapoviruses and
      rotaviruses were detected in 25% of MBR effluent samples with log reduction
      values of 3- and 2-logs in geometric mean concentrations, respectively, while
      noroviruses were detected in only 6% of the samples. We found that norovirus and
      sapovirus concentrations in the solid phase of mixed liquor samples were
      significantly higher than in the liquid phase (P < 0.01, t test), while the
      concentration of rotaviruses was similar in both phases. The efficiency of
      adsorption of the rotavirus G1P[8] strain to MLSS was significantly less than
      norovirus GI.1 and GII.4 and sapovirus GI.2 strains (P < 0.01, t test).
      Differences in the adsorption of viruses to MLSS may cause virus type-specific
      removal during the MBR treatment process as shown by this study.

PMID- 29214560
TI  - Invented Spelling, Word Stress, and Syllable Awareness in Relation to Reading
      Difficulties in Children.
AB  - The study assessed the clinical utility of an invented spelling tool and
      determined whether invented spelling with linguistic manipulation at segmental
      and supra-segmental levels can be used to better identify reading difficulties.
      We conducted linguistic manipulation by using real and nonreal words,
      incorporating word stress, alternating the order of consonants and vowels, and
      alternating the number of syllables. We recruited 60 third-grade students, of
      which half were typical readers and half were poor readers. The invented spelling
      task consistently differentiated those with reading difficulties from typical
      readers. It explained unique variance in conventional spelling, but not in word
      reading. Word stress explained unique variance in both word reading and
      conventional spelling, highlighting the importance of addressing phonological
      awareness at the supra-segmental level. Poor readers had poorer performance when
      spelling both real and nonreal words and demonstrated substantial difficulty in
      detecting word stress. Poor readers struggled with spelling words with double
      consonants at the beginning and ending of words, and performed worse on spelling
      two- and three-syllable words than typical readers. Practical implications for
      early identification and instruction are discussed.

PMID- 29214561
TI  - Environmental-Friendly and Facile Synthesis of Co3O4 Nanowires and Their
      Promising Application with Graphene in Lithium-Ion Batteries.
AB  - In this work, we developed an eco-friendly strategy for preparing Co3O4
      nanowires. The process consisted of two steps: controllable synthesis of metal
      cobalt nanowires followed by a facile air-oxidization step. The 1D nanowire
      structure with a high aspect ratio was easily achieved via a magnetic-field
      assisted self-assembly of cobalt ion complexes during reduction. After air
      calcinations, the Co3O4 nanowires were prepared in large scale and ready to be
      used as the anode material for lithium-ion batteries. The Co3O4 nanowires, which
      possessed a length ranging from 3 to 8 MUm with the aspect ratio more than 15,
      exhibited a reversible lithium storage capacity up to ~ 790 mAh/g when using a
      small amount of defect-free graphene flakes as conductive additives. The superior
      electrochemical performances were ascribable to the synergistic "flat-on" effect
      between the 1D nanowires and the 2D graphene. Therefore, the Co3O4
      nanowire/graphene composite holds promising application for lithium-ion
      batteries.

PMID- 29214562
TI  - Use of quantitative SPECT/CT reconstruction in 99mTc-sestamibi imaging of
      patients with renal masses.
AB  - OBJECTIVE: Technetium-99m (99mTc)-sestamibi single-photon emission computed
      tomography/computed tomography (SPECT/CT) has previously been shown to allow for
      the accurate differentiation of benign renal oncocytomas and hybrid
      oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor
      histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma
      (RCC) showing low uptake based on uptake ratios from non-quantitative single
      photon emission computed tomography (SPECT) reconstructions. However, in this
      study, several tumors fell close to the uptake ratio cutoff, likely due to
      limitations in conventional SPECT/CT reconstruction methods. We hypothesized that
      application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by
      our group would provide more robust separation of hot and cold lesions, serving
      as an imaging framework on which quantitative biomarkers can be validated for
      evaluation of renal masses with 99mTc-sestamibi. METHODS: Single-photon emission
      computed tomography data were reconstructed using the clinical Flash 3D
      reconstruction and QSPECT methods. Two blinded readers then characterized each
      tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing
      lesion activity by background renal activity for both Flash 3D and QSPECT
      reconstructions. RESULTS: The difference between median (mean) hot and cold tumor
      uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with
      the conventional method, resulting in increased separation between hot and cold
      tumors. Sub-analysis of 7 lesions near the separation point showed a higher
      absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios
      compared to the remaining lesions. CONCLUSIONS: Our finding of improved
      separation between uptake ratios of hot and cold lesions using QSPECT
      reconstruction lays the foundation for additional quantitative SPECT techniques
      such as SPECT-UV in the setting of renal 99mTc-sestamibi and other SPECT/CT
      exams. With robust quantitative image reconstruction and biomarker analysis,
      there may be an expanded role for SPECT/CT imaging in renal masses and other
      pathologic conditions.

PMID- 29214563
TI  - Rare Diseases: Joining Mainstream Research and Treatment Based on Reliable
      Epidemiological Data.
AB  - Despite growing acceptance of patient registries and natural history studies to
      provide useful information, the rare disease community suffers from the absence
      of reliable epidemiological data on the prevalence and incidence of most rare
      diseases in national and global populations. Likewise, the patients and health
      care providers lack adequate information on the pathophysiology of rare diseases
      and expected outcomes of these disorders. The rare diseases community includes
      all of the stakeholders involved in the research and development and
      dissemination of products and information for the diagnosis, prevention or
      treatment of rare diseases or conditions. To replace many of the perceptions with
      realities, several global efforts have been implemented to sustain and increase
      the reported progress with the thousands of rare diseases. The first efforts is
      to develop a global research infrastructure of qualified investigators to
      stimulate and coordinate research efforts by seeking ways to provide access to
      clinical trials at multi-national research sites with common protocols and multi
      disciplinary research teams. Next, is the continued identification and expansion
      of worldwide partnerships and collaborations of Patient Advocacy Groups (PAGs),
      research investigators, the biopharmaceutical and medical devices industries, and
      the government research and regulatory agencies for a specific rare disease or
      group of related diseases. Gaining access to information about rare diseases,
      patient advocacy groups, ongoing and planned research studies and products in
      research protocols continue to improve the lives of patients and their families.
      Many basic, clinical and translational research investigators, public and private
      sector funding organizations, patient advocacy groups, foundations, and the
      pharmaceutical, biotechnology, and medical devices industries are committed to
      translating research discoveries that will be useful in the treatment and care of
      patients with rare diseases over their lifespan. Evidence from well-constructed
      epidemiological studies will provide the evidence that point to the value of
      additional clinical studies to increase the understanding of rare diseases.

PMID- 29214564
TI  - Undiagnosed Diseases: Italy-US Collaboration and International Efforts to Tackle
      Rare and Common Diseases Lacking a Diagnosis.
AB  - Rare diseases (RD), according to European Union criteria, affect 5 per 10,000
      persons, or 30 million people, in the EU; in the USA, RD are defined as
      conditions that affect fewer than 200,000 individuals in the population (320
      million). Most known rare disorders are severe and chronic, with many being
      degenerative and life threatening. There are roughly 5000-8000 rare diseases
      (European Commission, DG Health and Food Safety, Public Health, Rare Diseases,
      Policy.http://ec.europa.eu/health/rare_diseases/policy/index_en.htm. Accessed 19
      December 2016; NORD-The National Organization for Rare Diseases:
      https://rarediseases.org/). Patient populations for individual RD are small and
      scattered; international collaborations are crucial to pool resources fragmented
      across individual countries for better diagnosis and treatment. Undiagnosed RD
      (URD) are conditions that elude diagnosis; some patients wait years for a
      definitive diagnosis. URD may include groups of unnamed disorders with common
      characteristics, phenotypically well described diseases, diseases with an unknown
      molecular basis, or those due to unknown, non-genetic factors.The US NIH
      Undiagnosed Diseases Program arose in 2008 to provide a diagnosis for individuals
      who had long sought one without success; in 2013 a nationwide Undiagnosed
      Diseases Network was established in the United States. In 2015, the Undiagnosed
      Disease Network International (UDNI) was established and includes US, Australia,
      Canada, Japan, Italy and other European countries. Other national initiatives
      have also been undertaken and are in progress all over the world.

PMID- 29214565
TI  - Intellectual Disability & Rare Disorders: A Diagnostic Challenge.
AB  - Rare disorders constitute a large and heterogeneous group of diagnoses of which
      many cause chronic disabilities with significant impact on the lives of affected
      individuals and their families as well as on the health-care system. Each
      individual disorder is rare, but when considered as a group, rare disorders are
      common with a total prevalence of approximately 6-8%. The clinical presentation
      of these disorders includes a broad diversity of symptoms and signs, often
      involving the nervous system and resulting in symptoms such as intellectual
      disability, neuropsychiatric disorders, epilepsy and motor dysfunction. The
      methods for establishing an etiological diagnosis in patients with rare disorders
      have improved dramatically during recent years. With the introduction of genomic
      screening methods, it has been shown that the cause is genetic in the majority of
      the patients and many will receive an etiological diagnosis in a clinical
      setting. However, there are a lot of challenges in diagnosing these disorders and
      despite recent years' advances, a large number of patients with rare disorders
      still go without an etiological diagnosis. In this chapter we will review the
      etiology of rare disorders with focus on intellectual disability and what has
      been learned from massive parallel sequencing studies in deciphering the genetic
      basis. Furthermore, we will discuss challenges in the etiological diagnostics of
      these disorders including issues that regard interpretation of the numerous
      genetic variants detected by genomic screening methods and challenges in the
      translation of massive parallel sequencing technologies into clinical practice.

PMID- 29214567
TI  - Natural History, Trial Readiness and Gene Discovery: Advances in Patient
      Registries for Neuromuscular Disease.
AB  - Inherited neuromuscular diseases (NMDs) are genetic disorders that affect the
      skeletal muscles or the nerves controlling muscle function. With a new generation
      of diagnostic options and recent advances in translational research improving the
      opportunities for therapy development for these rare conditions, capturing
      patient information in databases collecting a range of clinical and genetic data
      together with contact details has assumed an increasingly important role in trial
      planning and recruitment as well as natural history data collection. Here we
      provide an overview of a decade of patient registration activities in the NMD
      field, with a particular focus on patient registries set up with trial readiness
      in mind. A summary is provided of databases collecting precise genetic
      information focused on confirming the causative mutation and their evolution into
      registries that combine genetic data with additional clinical information useful
      for trial feasibility and recruitment. Use of these systems for a range of
      purposes beyond trial recruitment, including natural history assessment, care
      standards monitoring, genotype-phenotype correlation and disease burden
      evaluation is also described within the context of research networks (TREAT-NMD)
      and European Reference Networks (ERN-EURO-NMD). New initiatives including
      registries using controlled vocabularies for computational accessibility that
      focus on phenotypic data capture for gene discovery are analysed, and examples of
      the lessons learned at every stage are provided in order to allow new patient
      registration initiatives to benefit from the extensive experience gained.

PMID- 29214568
TI  - Facilitating Clinical Studies in Rare Diseases.
AB  - In recent years, there have been many scientific advances and new collaborations
      for rare diseases research and, ultimately, the health of patients living with
      rare diseases. However, for too many rare diseases, there still is no effective
      treatment, and our understanding of the incidence, prevalence, and underlying
      etiology is incomplete. To facilitate the studies needed to answer the many open
      questions there is a great need for the active involvement of all stakeholders,
      most importantly of patient groups. Also, the creation of streamlined
      infrastructure for performing multi-site clinical studies is critical, as is the
      engagement of multi-disciplinary teams with shared focus on a group of diseases.
      Another essential component of such efforts is to collect standardized data so
      that downstream meta-analyses and data sharing can be facilitated. To ensure high
      quality protocols and datasets, a central data management and coordinating center
      is important. Since there are more than 6000 rare diseases, instead of focusing
      on single rare disease, it is more impactful to create platforms and methods that
      can support a group of rare diseases.

PMID- 29214566
TI  - Improved Diagnosis and Care for Rare Diseases through Implementation of Precision
      Public Health Framework.
AB  - Public health relies on technologies to produce and analyse data, as well as
      effectively develop and implement policies and practices. An example is the
      public health practice of epidemiology, which relies on computational technology
      to monitor the health status of populations, identify disadvantaged or at risk
      population groups and thereby inform health policy and priority setting. Critical
      to achieving health improvements for the underserved population of people living
      with rare diseases is early diagnosis and best care. In the rare diseases field,
      the vast majority of diseases are caused by destructive but previously difficult
      to identify protein-coding gene mutations. The reduction in cost of genetic
      testing and advances in the clinical use of genome sequencing, data science and
      imaging are converging to provide more precise understandings of the 'person-time
      place' triad. That is: who is affected (people); when the disease is occurring
      (time); and where the disease is occurring (place). Consequently we are
      witnessing a paradigm shift in public health policy and practice towards
      'precision public health'.Patient and stakeholder engagement has informed the
      need for a national public health policy framework for rare diseases. The
      engagement approach in different countries has produced highly comparable
      outcomes and objectives. Knowledge and experience sharing across the
      international rare diseases networks and partnerships has informed the
      development of the Western Australian Rare Diseases Strategic Framework 2015-2018
      (RD Framework) and Australian government health briefings on the need for a
      National plan.The RD Framework is guiding the translation of genomic and other
      technologies into the Western Australian health system, leading to greater
      precision in diagnostic pathways and care, and is an example of how a precision
      public health framework can improve health outcomes for the rare diseases
      population.Five vignettes are used to illustrate how policy decisions provide the
      scaffolding for translation of new genomics knowledge, and catalyze
      transformative change in delivery of clinical services. The vignettes presented
      here are from an Australian perspective and are not intended to be comprehensive,
      but rather to provide insights into how a new and emerging 'precision public
      health' paradigm can improve the experiences of patients living with rare
      diseases, their caregivers and families.The conclusion is that genomic public
      health is informed by the individual and family needs, and the population health
      imperatives of an early and accurate diagnosis; which is the portal to best
      practice care. Knowledge sharing is critical for public health policy development
      and improving the lives of people living with rare diseases.

PMID- 29214569
TI  - Rare Disease Biospecimens and Patient Registries: Interoperability for Research
      Promotion, a European Example: EuroBioBank and SpainRDR-BioNER.
AB  - Well-annotated and properly preserved specimens are crucial both for diagnostic
      purposes and for use in basic and pre-clinical research, and are especially
      important for rare disease (RD) studies. Several consortia have been established
      in the recent years in order to facilitate research and to maximise access to
      rare biological samples and data stored in rare disease biobanks and registries,
      among them the EuroBioBank network and the Spain National Rare Disease Registry
      (RDR) and Biobank (BioNER).EuroBioBank, established in 2001, was the first
      network of RD biobanks to operate in Europe as a service distributing human DNA,
      cells, and tissue to the scientific community conducting research on rare
      diseases.The Spanish RDR and BioNER were created for facilitating rare disease
      research and health-related matters. The coordination of these two bodies
      represents an example of great scientific value as biological samples donated by
      patients at BioNER are linked to clinical information collected in the RDR.Rare
      disease biobanks and registries will need for the future to increase their effort
      to improve interconnection so to enable investigators to better locate samples
      and associated data, while protecting security of the data and privacy of the
      participants and adhering to international ethical and legal requirements.

PMID- 29214570
TI  - Data Quality in Rare Diseases Registries.
AB  - In the field of rare diseases, registries are considered power tool to develop
      clinical research, to facilitate the planning of appropriate clinical trials, to
      improve patient care and healthcare planning. Therefore high quality data of rare
      diseases registries is considered to be one of the most important element in the
      establishment and maintenance of a registry. Data quality can be defined as the
      totality of features and characteristics of data set that bear on its ability to
      satisfy the needs that result from the intended use of the data. In the context
      of registries, the 'product' is data, and quality refers to data quality, meaning
      that the data coming into the registry have been validated, and ready for use for
      analysis and research. Determining the quality of data is possible through data
      assessment against a number of dimensions: completeness, validity; coherence and
      comparability; accessibility; usefulness; timeliness; prevention of duplicate
      records. Many others factors may influence the quality of a registry: development
      of standardized Case Report Form and security/safety controls of informatics
      infrastructure. With the growing number of rare diseases registries being
      established, there is a need to develop a quality validation process to evaluate
      the quality of each registry. A clear description of the registry is the first
      step when assessing data quality or the registry evaluation system. Here we
      report a template as a guide for helping registry owners to describe their
      registry.

PMID- 29214571
TI  - Preparing Data at the Source to Foster Interoperability across Rare Disease
      Resources.
AB  - The ability to combine heterogeneous data distributed across the globe is
      critically important to boost research on rare diseases, but it presents a number
      of methodological, representational and automation challenges. In this scenario,
      biomedical ontologies are of critical importance for enabling computers to aid in
      information retrieval and analysis across data collections.This chapter presents
      an approach to preparing rare disease data for integration through the
      application of a global standard for computer-readable data and knowledge. This
      includes the use of common data elements, ontological codes and computer-readable
      data. This approach was developed under a number of domain-relevant requirements,
      such as controlled access to data, independence of the original sources, and the
      desire to combining the data sources with other computational workflows and data
      platforms.

PMID- 29214572
TI  - Incentivizing Orphan Product Development: United States Food and Drug
      Administration Orphan Incentive Programs.
AB  - Over 30 years ago, the United States (US) Congress passed the Orphan Drug Act
      (ODA) to encourage the development of products for rare diseases or conditions
      ("orphan products"). The Act provided incentives to sponsors for developing
      products with orphan designation and established a grant program to fund studies
      of orphan products. Since its enactment in 1983, the ODA has been credited for
      bringing more than 590 orphan drugs to the market, inspiring the implementation
      of orphan legislation globally, and enabling the creation of other programs that
      extend existing knowledge of the natural history of rare diseases and stimulate
      the development of medical devices for children and patients with rare diseases.
      This chapter provides a brief overview of the main features and successes of 5 of
      the orphan incentive programs administered by the US Food and Drug Administration
      (FDA): the Orphan Drug Designation Program, the Humanitarian Use Device (HUD)
      Designation Program, the Orphan Products Clinical Trials Grants Program, the
      Pediatric Device Consortia (PDC) Grant Program, and the Orphan Products Natural
      History Grants Program.

PMID- 29214573
TI  - Post-approval Studies for Rare Disease Treatments and Orphan Drugs.
AB  - Drug development involves a multi-stage process of drug discovery, animal studies
      and human clinical trials to assess the safety and efficacy of new medications.
      Rare disease drug development involves a much smaller number of affected
      patients, a predominance of pediatric patients and more complicated disease
      presentation. Post-approval studies are designed to address several limitations
      associated with the rare disease clinical trials.National and international
      regulatory agencies in the US and Europe have adopted similar approaches to
      requirements post-approval data for rare diseases and orphan drug indications.
      The US FDA published guidance in 2011 and the European Medicines Agency in
      2015.Post-approval studies for rare diseases include observational studies,
      pragmatic trials and randomized controlled studies. Observational studies include
      both original data collection studies and the use of secondary data
      (retrospective studies). Original data collection can address limitations of
      retrospective studies resulting from incomplete information in secondary data
      sources. Disease registries focus on detail about a broad range of patients with
      a rare disease while product-related registries focus on specific health care
      outcomes associated with a single product and may incorporate a comparator of an
      alternative therapy or therapies.Rare disease patients can be difficult to find
      and enroll in a registry using conventional physician based driven recruitment.
      The study process also needs to recognize changes in the patient's disease and
      lifestyle and adapt both the study design and methods over time. Many rare
      diseases have strong patient advocacy groups that can in aid the design and
      execution of rare disease registries.

PMID- 29214574
TI  - Evidence-Based Medicine and Rare Diseases.
AB  - This chapter discusses the meaning of evidence-based medicine and where it
      relates to randomised controlled trials, but also where it does not. The need for
      good quality evidence is stressed through a discussion of high failure rates in
      drug development and arguments against access to unlicensed (and largely
      untested) treatments are set out (despite the good intentions of those who
      advocate such access to treatments).Good quality, reliable evidence does not
      always have to come from clinical trials. Other forms of evidence are discussed.
      Meta-analyses of individual trials may help to resolve the problem that, in rare
      diseases, it may be very difficult or impossible to do adequately powered
      clinical trials - but that does not imply those trials have no value at all.The
      importance of patients' choices is stressed but the difficulties of making
      choices and the general poor understanding of risk can make patients and
      caregivers, as well as healthcare professionals, very vulnerable to making poor
      decisions. All stakeholders need to be adequately guided through the evidence to
      make proper informed decisions.

PMID- 29214575
TI  - Health Technology Assessment and Appraisal of Therapies for Rare Diseases.
AB  - Innovative rare disease therapies and health technology assessment (HTA) share a
      lot of similarities. Both represent cases of interaction of epidemiology and
      health economics. Both are relatively new topics in public health practice. And
      both pose a lot of challenges to rare disease stakeholders who are currently
      looking for tools to support the timely access to innovative treatments while
      putting budget spending in order. This is why optimisation of assessment and
      appraisal of new rare disease therapies is a fundamental issue in rare disease
      health policy. Rare disease patients and caregivers expect prolonged life
      expectancy and improved quality of life and they perceive innovative health
      technologies as a rightful way to achieve these objectives.Multi-criteria
      decision analysis (MCDA) provides a structured, transparent approach to identify
      preferred alternatives by means of combined calculation of relative importance of
      different criteria and performance of the alternatives on these criteria. The
      labyrinth of competing interests and numerous stakeholders involved is why
      innovative rare disease health technologies make an excellent case study of the
      integration between HTA and MCDA. This kind of formalisation of decision-making
      is perceived as fair and legitimate, leading to a balance and agreement. MCDA
      provides a stage for a debate of policy priorities, health system specifics and
      societal attitudes, while also addressing the impact of rarity on all criteria
      and considerations.

PMID- 29214576
TI  - New Therapeutic Uses for Existing Drugs.
AB  - Eighty percent of drugs that enter human clinical testing are never approved for
      use. This means that for every five drugs that make it into the clinic, there are
      four that failed to show effectiveness for treating the disease or condition the
      drug was designed to treat.This high failure rate means there are many existing,
      partially developed therapeutic candidates with known pharmacology, formulation,
      and potential toxicity. Finding new uses for existing experimental drugs or
      biologics "repositioning" builds upon previous research and development efforts,
      so new candidate therapies can be advanced to clinical trials for a new use more
      quickly than starting from scratch.Federal funding initiatives in the U.S. and UK
      started to support pre-clinical /or early stage trials for repositioning existing
      experimental drugs or biologics (therapies). This chapter covers some of the
      process issues that have been solved and the remaining challenges that are still
      in need of solutions. The chapter is primarily written from a U.S. federal
      funding perspective. The general concepts could be applied more globally to
      benefit rare and neglected disease populations. The drug development and process
      bottlenecks are the same for both rare and common disease.

PMID- 29214577
TI  - Patient Empowerment and Involvement in Research.
AB  - Patients with rare diseases often face difficulties in clinical care due to the
      low prevalence of their diseases and the resulting healthcare professionals' lack
      of expertise. Valid and standardized guidelines for clinical management are also
      lacking due to the scarcity of research and the variability of the clinical
      expressivity within each disease. In addition, in cases of rare diseases, the
      patient and health professional relationship may not fit with the traditional
      assumptions of medical care. Although the communication process between patients
      and healthcare professionals shares most of the general features of the standard
      patient-health professional interaction, rare diseases may be burdened with
      additional issues.In this sense, clinical decision-making in an uncertainty
      context should take advantage of involving patients in deeper informational
      process to promote valid shared decision-making between patients/caregivers and
      healthcare professionals. This process of patient/caregiver empowerment is a
      priority in the context of rare diseases, as it encourages acquisition of
      information that will help improving patient-healthcare professional's
      interaction, and building a collaborative relationship. It is also a chance for
      healthcare professionals to learn about rare diseases from the perspective of
      patients.Engagement of patients and other stakeholders in clinical research may
      help to ensure that research efforts in rare diseases address relevant clinical
      questions and patient-centered health outcomes. However, the effectiveness of
      patient-engagement approaches, particularly for the study of rare diseases, has
      not been well studied.

PMID- 29214578
TI  - Cost-Effectiveness Methods and Newborn Screening Assessment.
AB  - Nowadays, health funding decisions must be supported by sound arguments in terms
      of both effectiveness and economic criteria. After more than half a century of
      newborn screening for rare diseases, the appropriate economic evaluation
      framework for these interventions is still challenging. The validity of standard
      methods for economic evaluation heavily relies on the availability of robust
      evidence, but collection of such evidence is precluded by the rareness of the
      conditions that may benefit from screening. Furthermore, there are a series of
      conceptual and methodological limitations that warrant further careful
      consideration when assessing the cost-effectiveness of newborn screening
      programs. In this chapter we provide a general overview of current economic
      evaluation methods and the challenges for their application to newborn screening
      programs.

PMID- 29214579
TI  - Cost-of-Illness in Rare Diseases.
AB  - Cost-of-illness (COI) studies quantify the economic burden of a disease,
      including direct healthcare and non-healthcare costs and productivity losses.
      Different approaches can be adopted to evaluate the resources associated to a
      disease and to calculate the total costs. Prevalence-based studies estimate the
      total costs of a disease during a given period, while incidence-based studies
      measure lifetime costs from onset until death. Data can be collected from
      individuals, using a bottom-up approach, or from population statistics, using a
      top-down approach. Different perspectives are possible, but the broadest and also
      mostly used is the societal one. Appropriate discounting should be applied for
      future costs and a sensitivity analyses of main parameters should be performed.
      The main limitation of COI studies is that they don't account the outcomes or
      benefits of possible treatments.There is a lack of COI studies in the field of
      rare diseases. A multinational COI study (BURQOL-RD) evaluated recently the
      burden of 10 rare diseases in Europe, using a prevalence-based method with a
      bottom-up approach to quantify resources from a societal perspective, which is
      the mostly used methodology for COI studies in rare diseases; however, several
      other studies illustrate different approaches to conduct COI analysis in this
      field, such as incidence-based methods or narrower perspectives.COI studies are
      useful to inform policy-makers about the magnitude of a disease. To support
      correctly the decision-making process, it is necessary to identify the cost
      drivers through COI studies with robust design and standardized methodology.

PMID- 29214581
TI  - Newborn Screening: Beyond the Spot.
AB  - The newborn screening paradigm of testing all newborns in the United States for
      treatable conditions within the first few hours of birth has proven to be a
      remarkable success story in the realm of public health by reducing neonatal and
      childhood morbidity and mortality. The Newborn Screening Saves Lives Act of 2007
      and its successor, the Reauthorization Act of 2014, legislated the establishment
      of a Department of Health and Human Services Advisory Committee to make
      recommendations around newborn screening and a methodology to establish and add
      new conditions to a Recommended Uniform Screening Panel (RUSP) which currently
      includes 34 core conditions. In spite of the absence of a federal mandate that
      requires each of the states in the U.S. to screen for the disorders on the RUSP,
      most state public health laboratories have adopted the conditions on this panel.
      Moreover, the evolution of the evidence-based review process for adding new
      conditions to the RUSP has led to improvements in incorporating the public health
      impact and feasibility and implementation considerations. The cooperation between
      the federal partners who support implementation and rollout of state-based
      screening programs, develop technical standards and proficiency materials for
      laboratories, review and approve new technology platforms, and promote research
      to develop new assays and treatments for screenable disorders, points to the
      success of the newborn screening enterprise nationwide. As new technologic
      advances are made in the realm of genomic sequencing, the potential for
      incorporating these technologies holds great promise for newborn screening, but
      the ethical ramifications must be carefully considered to avoid harming the
      existing trust in the program.

PMID- 29214580
TI  - Primary Prevention of Congenital Anomalies: Special Focus on Environmental
      Chemicals and other Toxicants, Maternal Health and Health Services and Infectious
      Diseases.
AB  - Congenital anomalies (CA) represent an important fraction of rare diseases, due
      to the critical role of non-genetic factors in their pathogenesis. CA are the
      main group of rare diseases in which primary prevention measures will have a
      beneficial impact. Indeed, since 2013 the European Union has endorsed a body of
      evidence-based recommendations for CA primary prevention; the recommendations aim
      at facilitating the inclusion of primary prevention actions the National Rare
      Disease Plans of EU Member States and encompass different public health fields,
      from environment through to maternal diseases and lifestyles.The chapter
      overviews and discusses the assessment of main risk factors for CA, such as
      environmental toxicants, maternal health and lifestyles and infections, with a
      special attention to issues that are emerging or need more knowledge.Overall, the
      availability of CA registries is important for estimating the health burden of
      CA, identifying possible hotspots, assessing the impact of interventions and
      addressing further, fit-to-purpose research.The integration of relevant public
      health actions that are already in place (e.g., control of noxious chemicals,
      vaccination programmes, public health services addressing chronic maternal
      conditions) can increase the affordability and sustainability of CA primary
      prevention. In developing countries with less primary prevention in place and
      limited overall resources, a first recognition phase may be pivotal in order to
      identify priority targets. In the meanwhile, policy makers should be made aware
      that primary prevention of RD supports publicly endorsed societal values like the
      knowledge-based promotion of health, empowerment, equity and social
      inclusiveness.

PMID- 29214582
TI  - A Global Approach to Rare Diseases Research and Orphan Products Development: The
      International Rare Diseases Research Consortium (IRDiRC).
AB  - Rare diseases present unique challenges to researchers due to the global
      distribution of patients, complexity and low prevalence of each disease, and
      limited availability of data. They are also overwhelming and costly for patients,
      their families, communities, and society. As such, global integration of rare
      diseases research is necessary to accelerate the understanding, diagnosis, and
      treatment of rare disorders. The International Rare Diseases Research Consortium
      (IRDiRC) was born out of that need for a coordinated international community.
      IRDiRC was launched in 2011 to facilitate cooperation and collaboration on a
      global scale among the many stakeholders active in rare diseases research to
      stimulate better coordination, and thereby maximize output of rare diseases
      research efforts around the world. Members include funders, academic researchers,
      companies, and patient advocacy organizations all of whom share the common goals
      and principles of IRDiRC. The overarching objectives of the Consortium are to
      contribute to the development of 200 new therapies and a means to diagnose most
      rare diseases, by 2020. As IRDiRC approaches the end of its fifth year, these
      initial objectives have been largely achieved and new partners from across the
      globe are joining. This presents the Consortium with the exciting opportunity to
      set new and even more ambitious goals for the next phase with the ultimate goal
      of improved health through faster and better diagnostic capabilities and novel
      therapies for people living with rare diseases and conditions throughout the
      world.

PMID- 29214583
TI  - Prospects of Pluripotent and Adult Stem Cells for Rare Diseases.
AB  - Rare diseases are highly diverse and complex regarding molecular underpinning and
      clinical manifestation and afflict millions of patients worldwide. The lack of
      appropriate model systems with face and construct validity and the limited
      availability of live tissues and cells from patients has largely hampered the
      understanding of underlying disease mechanisms. As a consequence, there are no
      adequate treatment options available for the vast majority of rare diseases. Over
      the last decade, remarkable progress in pluripotent and adult stem cell biology
      and the advent of powerful genomic technologies opened up exciting new avenues
      for the investigation, diagnosis, and personalized therapy of intractable human
      diseases. Utilizing the entire range of available stem cell types will continue
      to cross-fertilize different research areas and leverage the investigation of
      rare diseases based on evidence-based medicine. Standardized cell engineering and
      manufacturing from inexhaustible stem cell sources should lay the foundation for
      next-generation drug discovery and cell therapies that are broadly applicable in
      regenerative medicine. In this chapter we discuss how patient- and disease
      specific iPS cells as well as adult stem cells are changing the pace of
      biomedical research and the translational landscape.

PMID- 29214584
TI  - Personalized Medicine: What's in it for Rare Diseases?
AB  - Personalised Medicine has become a reality over the last years. The emergence of
      'omics' and big data has started revolutionizing healthcare. New 'omics'
      technologies lead to a better molecular characterization of diseases and a new
      understanding of the complexity of diseases. The approach of PM is already
      successfully applied in different healthcare areas such as oncology, cardiology,
      nutrition and for rare diseases. However, health systems across the EU are often
      still promoting the 'one-size fits all' approach, even if it is known that
      patients do greatly vary in their molecular characteristics and response to drugs
      and other interventions. To make use of the full potentials of PM in the next
      years ahead several challenges need to be addressed such as the integration of
      big data, patient empowerment, translation of basic to clinical research,
      bringing the innovation to the market and shaping sustainable healthcare systems.

PMID- 29214585
TI  - Microphysiological Systems (Tissue Chips) and their Utility for Rare Disease
      Research.
AB  - The scientific and technological development of microphysiological systems (MPS)
      modeling organs-on-chips, or "tissue chips" (TCs), has progressed rapidly over
      the past decade. Stem cell research and microfluidic concepts have combined to
      lead to the development of microphysiological platforms representing an ever
      expanding list of different human organ systems. In the context of rare diseases,
      these bioengineered microfluidics platforms hold promise for modeling of
      disorders and could prove useful in the screening and efficacy testing of
      existing therapeutics. Additionally, they have the potential for replacing and
      refining animal use for new drugs and clinical treatments, or could even act as
      surrogate human systems for testing of new therapeutics in the future, which
      could be particularly useful in populations of rare disease sufferers. This
      chapter will discuss the current state of tissue chip research, and challenges
      facing the field. Additionally, we will discuss how these devices are being used
      to model basic cellular and molecular phenotypes of rare diseases, holding
      promise to provide new tools for understanding of disease pathologies and
      screening and efficacy testing of potential therapeutics for drug discovery.

PMID- 29214586
TI  - Epidemiology of Rare Lung Diseases: The Challenges and Opportunities to Improve
      Research and Knowledge.
AB  - Rare lung diseases encompass a broad spectrum of conditions and affect an
      estimated 1.2-2.5 million people in North America and 1.5-3 million people in
      Europe. While individual rare lung diseases affect less than 1 in 2000
      individuals, collectively they have a significant impact upon the population at
      large. Hence it is vital to understand firstly the epidemiology and subsequently
      the pathogenesis and clinical course of these disorders. Through a greater
      understanding of these aspects of disease, progress can be made in reducing
      symptoms, containing healthcare costs and utilizing resources efficiently.
      Furthermore, a greater understanding of the pathobiology of rare lung diseases
      can inform both the pathogenesis and management of more common pulmonary
      disorders.In this chapter we review how epidemiological approaches and the
      utilization of patient registries has improved the knowledge and management of
      rare lung diseases. We further focus on the epidemiology of several of the more
      widely known rare pulmonary disorders, including idiopathic pulmonary fibrosis
      (IPF), cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (AATD). To
      conclude we describe how patient advocacy groups and foundations have driven
      advances in research and management of ultra-rare lung diseases, namely, the
      major strides made in the management and understanding of
      lymphangioleiomyomatosis (LAM) and pulmonary alveolar proteinosis (PAP).We
      conclude that the models used to study some of the rarest of diseases may be
      successfully adopted by other rare and common disease communities, leading to
      improved care and the possibility of novel therapeutic options.

PMID- 29214587
TI  - Rare Neurodegenerative Diseases: Clinical and Genetic Update.
AB  - More than 600 human disorders afflict the nervous system. Of these,
      neurodegenerative diseases are usually characterised by onset in late adulthood,
      progressive clinical course, and neuronal loss with regional specificity in the
      central nervous system. They include Alzheimer's disease and other less frequent
      dementias, brain cancer, degenerative nerve diseases, encephalitis, epilepsy,
      genetic brain disorders, head and brain malformations, hydrocephalus, stroke,
      Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS or
      Lou Gehrig's Disease), Huntington's disease, and Prion diseases, among others.
      Neurodegeneration usually affects, but is not limited to, the cerebral cortex,
      intracranial white matter, basal ganglia, thalamus, hypothalamus, brain stem, and
      cerebellum. Although the majority of neurodegenerative diseases are sporadic,
      Mendelian inheritance is well documented. Intriguingly, the clinical
      presentations and neuropathological findings in inherited neurodegenerative forms
      are often indistinguishable from those of sporadic cases, suggesting that
      converging genomic signatures and pathophysiologic mechanisms underlie both
      hereditary and sporadic neurodegenerative diseases. Unfortunately, effective
      therapies for these diseases are scarce to non-existent. In this chapter, we
      highlight the clinical and genetic features associated with the rare inherited
      forms of neurodegenerative diseases, including ataxias, multiple system atrophy,
      spastic paraplegias, Parkinson's disease, dementias, motor neuron diseases, and
      rare metabolic disorders.

PMID- 29214588
TI  - Immunological Rare Diseases.
AB  - The immune system is delegated to defend the body from attacks from outside or
      inside. Many diseases can affect immune system reducing its ability to defend
      self or inducing an abnormal response against external or internal antigens. Rare
      diseases affecting immune system present some issue in common with other rare
      diseases and some peculiarities due to the huge variability in the disease's
      expression. However, a correct estimation of the epidemiology of rare disorders
      is necessary for evaluating the prognosis and the responses to new therapies, for
      planning proper public health services, and finally to establish fair and
      sustainable prices for innovative medicines. Due to the enormous number of
      different rare immunological diseases, in this chapter we are going to analyse
      some of them that can be considered paradigmatic of the various expressions of
      disease.

PMID- 29214589
TI  - Indigenous Genetics and Rare Diseases: Harmony, Diversity and Equity.
AB  - Advances in our understanding of genetic and rare diseases are changing the face
      of healthcare. Crucially, the global community must implement these advances
      equitably to reduce health disparities, including between Indigenous and non
      Indigenous peoples. We take an Australian perspective to illustrate some key
      areas that are fundamental to the equitable translation of new knowledge for the
      improved diagnosis of genetic and rare diseases for Indigenous people.
      Specifically, we focus on inequalities in access to clinical genetics services
      and the lack of genetic and phenomic reference data to inform diagnoses. We
      provide examples of ways in which these inequities are being addressed through
      Australian partnerships to support a harmonious and inclusive approach to ensure
      that benefits from traditional wisdom, community knowledge and shared experiences
      are interwoven to support and inform implementation of new knowledge from
      genomics and precision public health. This will serve to deliver benefits to all
      of our diverse citizens, including Indigenous populations.

PMID- 29214590
TI  - Mortality Statistics and their Contribution to Improving the Knowledge of Rare
      Diseases Epidemiology: The Example of Hereditary Ataxia in Europe.
AB  - Official mortality statistics provide population-based data and serve to improve
      epidemiological knowledge of rare diseases (RDs), by helping with the description
      of the natural history of the disease. They are an important complement of
      registries and estimates of disease burden and costs. At the same time, they
      heighten both the visibility of these diseases and the interest in their study
      and the search for treatments that may increase survival. This chapter contains a
      European analysis of hereditary ataxia mortality, which considers the time trend
      in different countries and the geographical variability in risk of death. Despite
      the limitations of applying this data source to RDs, mortality statistics share
      criteria which facilitate international comparisons and are of great utility for
      obtaining sufficiently uniform and robust time series for analysis of low
      prevalence diseases.

PMID- 29214591
TI  - Congenital Anomalies: Cluster Detection and Investigation.
AB  - This work summarizes the main aspects to be considered around birth defects (or
      congenital anomalies) clusters. Most birth defects (BD), considered individually,
      fall into the definition of rare diseases (RD), according to their low frequency.
      Likewise, many RD are congenital, because their manifestations are present at
      birth or can be even evident before the delivery. It has been estimated that
      overall 7.9 million children are born each year with serious BD of genetic or
      partially genetic origin, and additional hundreds of thousands more are born with
      serious BD of post-conception origin.A "birth defect cluster" can be defined as
      an unusual aggregation of cases (grouped in place and time) that is suspected to
      be greater than expected, even though the expected number may not be known. These
      clusters are incidents or occurrences that let us turn the challenge of
      identifying the causal agent(s) involved in the origin of such clusters, into an
      opportunity to exert primary prevention, and thus achieve the ultimate goal of
      enabling infants being born healthy. Therefore, any program or system involved in
      BD surveillance and research should devote part of its activities to detect and
      investigate clusters, to ensure that such opportunity for primary prevention will
      be conveniently leveraged. Regardless the type of cluster, there are several
      phases that must be undertaken sequentially for proper control and the maximum
      benefit for the population: cluster detection, evaluation and investigation,
      management, adoption of preventive measures, and communication of the results to
      the public or target population.

PMID- 29214592
TI  - The European Union Policy in the Field of Rare Diseases.
AB  - Rare diseases, are defined by the European Union as life-threatening or
      chronically debilitating diseases with low prevalence (less than 5 per 10,000).
      The specificities of rare diseases - limited number of patients and scarcity of
      relevant knowledge and expertise - single them out as a unique domain of very
      high European added-value.The legal instruments at the disposal of the European
      Union, in terms of the Article 168 of the Treaties, are very limited. However a
      combination of instruments using the research and the pharmaceutical legal basis
      and an intensive and creative use of funding from the Health Programmes has
      permitted to create a solid basis that Member States have considered enough to
      put rare diseases in a privileged position in the health agenda.The adoption of
      the Commission Communication, in November 2008, and of the Council
      Recommendation, in June 2009, and in 2011 the adoption of the Directive on Cross
      border healthcare., have created an operational framework to act in the field of
      rare disease with European coordination in several areas (classification and
      codification, European Reference Networks, orphan medicinal products, the
      Commission expert group on rare diseases, etc.).Rare diseases is an area with
      high and practical potential for the European cooperation.

PMID- 29214593
TI  - The Role of Solidarity(-ies) in Rare Diseases Research.
AB  - Solidarity plays a relevant role in rare diseases (RDs) research to create and
      enable research in the field. In Europe RDs are estimated to affect between 27
      and 36 million people even though single RDs can count very few patients, making
      the contribution of everyone essential to reach solid results. Often RD research
      is initiated by patient groups devoting substantial time and resources to the
      scientific enterprise. In RD research solidarity is often evocated and expressed,
      in different ways and on different levels, so that it is possible to talk about
      "solidarities" played by different stakeholders and sometimes conflicting with
      each other. In this paper we describe different contexts in which solidarity is
      expressed and embedded in RD research, in particular the context of tight
      relationships between individuals and their families or in small
      communities/ethnic groups; among individuals suffering from different RDs and
      researchers working on a specific RD or a group of RDs, and within society at
      large. In all these cases the different types of solidarity should be balanced
      against each other and also against conflicting values. The request to a patient
      to share data and samples to increase scientific knowledge on the basis of
      solidarity values needs to be balanced against the need to protect her privacy
      and autonomy; the duty for a researcher to allow fair access to RD sample and
      data collections which were donated in a spirit of solidarity is balanced against
      the need to be competitive in the research world. In the Report "Solidarity.
      Reflections on an emerging concept in bioethics", the Nuffield Council of
      Bioethics defines solidarity as "shared practices reflecting a collective
      commitment to carry 'costs' (financial, social, emotional or otherwise) to assist
      others". Therefore, if a solidarity framework has to be solid and ethically sound
      it needs to be framed as a shared value, reflected in the different practices by
      all the stakeholders and be based on reciprocity (not one sided). The context of
      solidarity(ies) provides a solid base for framing the research endeavor as
      collectively valuable, not only for possible results of the research, but as
      intrinsic valid societal practice. This paper tries to draw the lessons on
      solidarity that we can derive from the RD world where "solidarities" have been
      part of the game for long time and are declined on many different levels.

PMID- 29214594
TI  - Bridging the Gap between Health and Social Care for Rare Diseases: Key Issues and
      Innovative Solutions.
AB  - Bridging the gaps between health and social care for rare diseases is not only
      necessary but crucial to increase the life expectancy, quality of life and
      autonomy of people living with a rare disease, supporting them in the full
      realisation of their fundamental human rights.The complexity of rare diseases,
      their strong relation to disability and the current unmet social and daily life
      needs of people living with a rare disease must not be underestimated and require
      urgent attention from all stakeholders involved in care provision, from
      healthcare to social and community services.The Commission Expert Group
      Recommendations to Support the Incorporation of Rare Diseases into Social
      Services and Policies, adopted unanimously in April 2016, by the representatives
      of European Member States and the other rare disease stakeholders, clearly set
      the tone for the need to promote measures that facilitate multidisciplinary,
      holistic, continuous, person-centred and participative care provision to people
      living with rare diseases.These recommendations, sided by other recent policy
      developments at European and national levels, represent an important policy step
      into approaching rare diseases' complex challenges in regards to holistic care
      provision.Innovative approaches aiming at bridging the gap between health, social
      and community service and support providers are currently being developed and
      tested in different European countries: standards of care, networks of expertise,
      case management services, one-stop-shop services, amongst others.These ongoing
      pilot approaches, presented in this chapter, have the power to inspire future
      policies and the effective and efficient implementation of holistic care pathways
      for people living with a rare disease, bringing about significant changes for
      patients, carers, care providers, competent authorities and the society at
      large.Nonetheless, the challenges to fully address this issue remain numerous and
      other key issues will also need to be taken into account when moving forward with
      the implementation of measures that aim at bridging the gaps between care
      providers and providing holistic care to people living with a rare disease.

PMID- 29214595
TI  - Health Systems Sustainability and Rare Diseases.
AB  - The paper is addressing aspects of health system sustainability for rare diseases
      in relation to the current economic crisis and equity concerns. It takes into
      account the results of the narrative review carried out in the framework of the
      Joint Action for Rare Diseases (Joint RD-Action) "Promoting Implementation of
      Recommendations on Policy, Information and Data for Rare Diseases", that
      identified networks as key factors for health systems sustainability for rare
      diseases. The legal framework of European Reference Networks and their added
      value is also presented. Networks play a relevant role for health systems
      sustainability, since they are based upon, pay special attention to and can
      intervene on health systems knowledge development, partnership, organizational
      structure, resources, leadership and governance. Moreover, sustainability of
      health systems can not be separated from the analysis of the context and the
      action on it, including fiscal equity. As a result of the financial crisis of
      2008, cuts of public health-care budgets jeopardized health equity, since the
      least wealthy suffered from the greatest health effects. Moreover, austerity
      policies affected economic growth much more adversely than previously believed.
      Therefore, reducing public health expenditure not only is going to jeopardise
      citizens' health, but also to hamper fair and sustainable development.

PMID- 29214596
TI  - Preparing for the Future of Rare Diseases.
AB  - Members of the rare disease community have devoted significant financial and
      personnel resources to address the numerous issues surrounding rare diseases. The
      past has been devoted to developing an emphasis on rare diseases including an
      emphasis on research studies or locating information on rare diseases and the
      requirements and limitations of conducting clinical trials with small patient
      populations. The expanded role of patient advocacy organizations and patient
      engagement in all aspects of clinical research continues to gain acceptance
      within the research community. The future will require a greater understanding
      and interpretation of available information from multiple sources including
      electronic health records and big data sources. The pipeline of potential orphan
      products continues to grow significantly and holds great promise for novel
      interventions due to advances in clinical trial design and data analyses.
      Expanding diagnostic procedures with improved sequencing methods will speed up
      the diagnosis or rare diseases. Accepting agreed upon nomenclature and
      codification of rare diseases will assist in differentiating diseases and
      identifying selected sub-populations of rare diseases. Improvements in patient
      recruitment and increased flexibility in the product review and approval
      procedures by regulatory agencies will facilitate product approvals. Children
      particularly will need help and assistance dealing with feelings of isolation
      from their peers due to their rare disease. During the transition from childhood
      to adolescence to adult, difficulties of fitting in with peers and not wanting to
      be different are a major concern. In response to increasing costs of treatments,
      Value-Based Care is gaining greater acceptance by the reimbursement and the payer
      community as a basis for payment for interventions. Mobile Health (M-health)
      Technologies have the potential to revolutionize how clinical research is
      conducted in the future. Wearable devices, remote sensors, and the development of
      mobile device applications (apps) will all assist in constant monitoring of
      patients for safety and efficacy of approved and investigational compounds. Tele
      Health and Tele Medicine may provide the necessary access to expert clinicians
      with a better understanding of individual rare diseases. The future promises
      great advances and even greater personalized treatments with the introduction of
      novel treatments and approaches to care.

PMID- 29214597
TI  - Fabrication and Characterization of New Composite Tio2 Carbon Nanofiber Anodic
      Catalyst Support for Direct Methanol Fuel Cell via Electrospinning Method.
AB  - Platinum (Pt) is the common catalyst used in a direct methanol fuel cell (DMFC).
      However, Pt can lead towards catalyst poisoning by carbonaceous species, thus
      reduces the performance of DMFC. Thus, this study focuses on the fabrication of a
      new composite TiO2 carbon nanofiber anodic catalyst support for direct methanol
      fuel cells (DMFCs) via electrospinning technique. The distance between the tip
      and the collector (DTC) and the flow rate were examined as influencing parameters
      in the electrospinning technique. To ensure that the best catalytic material is
      fabricated, the nanofiber underwent several characterizations and electrochemical
      tests, including FTIR, XRD, FESEM, TEM, and cyclic voltammetry. The results show
      that D18, fabricated with a flow rate of 0.1 mLhr-1 and DTC of 18 cm, is an
      ultrafine nanofiber with the smallest average diameter, 136.73 +/- 39.56 nm. It
      presented the highest catalyst activity and electrochemical active surface area
      value as 274.72 mAmg-1 and 226.75m2 g-1PtRu, respectively, compared with the
      other samples.

PMID- 29214598
TI  - Evaluation of a wireless, portable, wearable multi-parameter vital signs monitor
      in hospitalized neurological and neurosurgical patients.
AB  - Unrecognized changes in patients' vital signs can result in preventable deaths in
      hospitalized patients. Few publications or studies instituting routine patient
      monitoring have described implementation and the setting of alarm parameters for
      vital signs. We wanted to determine if continuous multi-parameter patient
      monitoring can be accomplished with an alarm rate that is acceptable to hospital
      floor nurses and to compare the rate of patient deterioration events to those
      observed with routine vital sign monitoring. We conducted a prospective,
      observational, 5-month pilot study in a 26-bed adult, neurological/neurosurgical
      unit (non-ICU) in an academic medical center. A patient surveillance system
      employing a wireless body-worn vital signs monitor with automated nursing
      notification of alarms via smartphones was used to gather data. Data collected
      included: alarm rates, rapid response team (RRT) calls, intensive care unit (ICU)
      transfers, and unplanned deaths before and during the pilot study. Average alarm
      rate for all alarms (SpO2, HR, RR, NIBP) was 2.3 alarms/patient/day. The RRT call
      rate was significantly reduced (p < 0.05) from 189 to 158 per 1000 discharges.
      ICU transfers per 1000 discharges were insignificantly reduced from 53 to 40
      compared to the previous 5-month period in the same unit. Similar measures of
      comparison units did not change over the same period. Although unplanned patient
      deaths in the study unit were also reduced during the intervention period, this
      was not statistically significant. Continual, multi-parameter vital signs
      monitoring can be customized to reduce a high alarm rates, and may reduce rapid
      response team calls.

PMID- 29214599
TI  - Protein tyrosine phosphatase 1B inhibitors from natural sources.
AB  - Since PTP1B enzyme was discovered in 1988, it has captured the research
      community's attention. This landmark discovery has stimulated numerous research
      studies on a variety of human diseases, including cancer, inflammation, and
      diabetes. Tremendous progress has been made in finding PTP1B inhibitors and
      exploring PTP1B regulatory mechanisms. This review investigates for the natural
      PTP1B inhibitors, and focuses on the common characteristics of the discovered
      structures and structure-activity relationships. To facilitate understanding, all
      the natural compounds are here divided into five different classes (fatty acids,
      phenolics, terpenoids, steroids, and alkaloids), according to their skeletons.
      These PTP1B inhibitors of scaffold structures could serve as a theoretical basis
      for new concept drug discovery and design.

PMID- 29214600
TI  - Apoptosis induction by alantolactone in breast cancer MDA-MB-231 cells through
      reactive oxygen species-mediated mitochondrion-dependent pathway.
AB  - Alantolactone is a sesquiterpene lactone isolated from Inula helenium L. Although
      alantolactone possesses anti-inflammation and apoptosis-induction activities, the
      underlying mechanism of anti-cancer effect on human breast cancer cells remains
      largely unknown. In this study, we explored the possibility of alantolactone as
      an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells as in vitro model.
      Alantolactone significantly induced its apoptosis, demonstrated by cell cycle
      analysis, annexin V-APC/7-AAD double staining and dUTP nick end labeling.
      Additionally, alantolactone triggered the mitochondrial-mediated caspase cascade
      apoptotic pathway, which was confirmed by increased Bax/Bcl-2 ratio, loss of MMP,
      release of cytc from mitochondria to cytoplasm, activation of caspase 9/3, and
      subsequent cleavage of PARP. Z-VAD-FMK partially prevented apoptosis induced by
      alantolactone. Alantolactone provoked the production of ROS, while NAC (a
      scavenger of ROS) reversed alantolactone-mediated depolarization of MMP and
      apoptosis. Alantolactone modulated the activities of MAPKs. As expected,
      cotreatment with SB203580, SP600125 or U0126 could reduced the apoptotic rate.
      Furthermore, alantolactone decreased the protein expressions of p-NF-kB p65 and p
      STAT3, increased p-c-Jun level in a dose-dependent manner. These findings
      suggested that alantolactone possessed anticancer activity via ROS-mediated
      mitochondrial dysfunction involving MAPK pathway, and had an effect on the
      transcription factors of NF-kB, AP-1 and STAT3.

PMID- 29214601
TI  - Emerging potential of stimulus-responsive nanosized anticancer drug delivery
      systems for systemic applications.
AB  - The development of novel drug delivery systems based on well-defined polymer
      therapeutics has led to significant improvements in the treatment of multiple
      disorders. Advances in material chemistry, nanotechnology, and nanomedicine have
      revolutionized the practices of drug delivery. Stimulus-responsive material-based
      nanosized drug delivery systems have remarkable properties that allow them to
      circumvent biological barriers and achieve targeted intracellular drug delivery.
      Specifically, the development of novel nanocarrier-based therapeutics is the need
      of the hour in managing complex diseases. In this review, we have briefly
      described the fundamentals of drug targeting to diseased tissues, physiological
      barriers in the human body, and the mechanisms/modes of drug-loaded carrier
      systems. To that end, this review serves as a comprehensive overview of the
      recent developments in stimulus-responsive drug delivery systems, with focus on
      their potential applications and impact on the future of drug delivery.

PMID- 29214603
TI  - Documenting and Understanding Parent's Intervention Choices for Their Child with
      Autism Spectrum Disorder.
AB  - Understanding why parents choose some interventions but not others for their
      child with autism is important for a number of reasons. Estimating the proportion
      of evidence-based interventions engaged, identifying the agencies influencing
      parental decisions, and elucidating the barriers or reasons leading to
      intervention rejection or discontinuation can result in better service provision.
      New Zealand parents (n = 570) of a child with autism reported what interventions
      were being engaged, and why some interventions were engaged but not others.
      Funding was a major determinant of intervention engagement, while medical
      professionals exerted the most influence. Sources of support were not related to
      intervention engagement, but parental perceptions of their child's symptom
      severity were. Finally, non-engagement does not necessarily reflect parental
      opposition to an intervention, but rather the existence of barriers.

PMID- 29214602
TI  - Peromyscus maniculatus bairdii as a naturalistic mammalian model of obsessive
      compulsive disorder: current status and future challenges.
AB  - Obsessive-compulsive disorder (OCD) is a prevalent and debilitating condition,
      characterized by intrusive thoughts and repetitive behavior. Animal models of OCD
      arguably have the potential to contribute to our understanding of the condition.
      Deer mice (Permomyscus maniculatus bairdii) are characterized by stereotypic
      behavior which is reminiscent of OCD symptomology, and which may serve as a
      naturalistic animal model of this disorder. Moreover, a range of deer mouse
      repetitive behaviors may be representative of different compulsive-like
      phenotypes. This paper will review work on deer mouse behavior, and evaluate the
      extent to which this serves as a valid and useful model of OCD. We argue that
      findings over the past decade indicate that the deer mouse model has face,
      construct and predictive validity.

PMID- 29214604
TI  - Abilities to Explicitly and Implicitly Infer Intentions from Actions in Adults
      with Autism Spectrum Disorder.
AB  - Previous research suggests that Autism Spectrum Disorder (ASD) might be
      associated with impairments on implicit but not explicit mentalizing tasks.
      However, such comparisons are made difficult by the heterogeneity of stimuli and
      the techniques used to measure mentalizing capabilities. We tested the abilities
      of 34 individuals (17 with ASD) to derive intentions from others' actions during
      both explicit and implicit tasks and tracked their eye-movements. Adults with ASD
      displayed explicit but not implicit mentalizing deficits. Adults with ASD
      displayed typical fixation patterns during both implicit and explicit tasks.
      These results illustrate an explicit mentalizing deficit in adults with ASD,
      which cannot be attributed to differences in fixation patterns.

PMID- 29214605
TI  - Creation of artificial protein-protein interactions using alpha-helices as
      interfaces.
AB  - Designing novel protein-protein interactions (PPIs) with high affinity is a
      challenging task. Directed evolution, a combination of randomization of the gene
      for the protein of interest and selection using a display technique, is one of
      the most powerful tools for producing a protein binder. However, the selected
      proteins often bind to the target protein at an undesired surface. More
      problematically, some selected proteins bind to their targets even though they
      are unfolded. Current state-of-the-art computational design methods have
      successfully created novel protein binders. These computational methods have
      optimized the non-covalent interactions at interfaces and thus produced
      artificial protein complexes. However, to date there are only a limited number of
      successful examples of computationally designed de novo PPIs. De novo design of
      coiled-coil proteins has been extensively performed and, therefore, a large
      amount of knowledge of the sequence-structure relationship of coiled-coil
      proteins has been accumulated. Taking advantage of this knowledge, de novo design
      of inter-helical interactions has been used to produce artificial PPIs. Here, we
      review recent progress in the in silico design and rational design of de novo
      PPIs and the use of alpha-helices as interfaces.

PMID- 29214606
TI  - Recent progress on understanding the mechanisms of amyloid nucleation.
AB  - Amyloid fibrils are supramolecular protein assemblies with a fibrous morphology
      and cross-beta structure. The formation of amyloid fibrils typically follows a
      nucleation-dependent polymerization mechanism, in which a one-step nucleation
      scheme has widely been accepted. However, a variety of oligomers have been
      identified in early stages of fibrillation, and a nucleated conformational
      conversion (NCC) mechanism, in which oligomers serve as a precursor of amyloid
      nucleation and convert to amyloid nuclei, has been proposed. This development has
      raised the need to consider more complicated multi-step nucleation processes in
      addition to the simplest one-step process, and evidence for the direct
      involvement of oligomers as nucleation precursors has been obtained both
      experimentally and theoretically. Interestingly, the NCC mechanism has some
      analogy with the two-step nucleation mechanism proposed for inorganic and organic
      crystals and protein crystals, although a more dramatic conformational conversion
      of proteins should be considered in amyloid nucleation. Clarifying the properties
      of the nucleation precursors of amyloid fibrils in detail, in comparison with
      those of crystals, will allow a better understanding of the nucleation of amyloid
      fibrils and pave the way to develop techniques to regulate it.

PMID- 29214607
TI  - Generation and propagation of yeast prion [URE3] are elevated under
      electromagnetic field.
AB  - In this study, we studied the effect of 2.0 GHz radio frequency electromagnetic
      field (RF-EMF) and 50 Hz extremely low frequency electromagnetic field (ELF-EMF)
      exposure on prion generation and propagation using two budding yeast strains,
      NT64C and SB34, as model organisms. Under exposure to RF-EMF or ELF-EMF, the de
      novo generation and propagation of yeast prions [URE3] were elevated in both
      strains. The elevation increased over time, and the effects of ELF-EMF occurred
      in a dose-dependent manner. The transcription and expression levels of the
      molecular chaperones Hsp104, Hsp70-Ssa1/2, and Hsp40-Ydj1 were not statistically
      significantly changed after exposure. Furthermore, the levels of ROS, as well as
      the activities of superoxide dismutase (SOD) and catalase (CAT), were
      significantly elevated after short-term, but not long-term exposure. This work
      demonstrated for the first time that EMF exposure could elevate the de novo
      generation and propagation of yeast prions and supports the hypothesis that ROS
      may play a role in the effects of EMF on protein misfolding. The effects of EMF
      on protein folding and ROS levels may mediate the broad effects of EMF on cell
      function.

PMID- 29214608
TI  - A Science and Risk-Based Pragmatic Methodology for Blend and Content Uniformity
      Assessment.
AB  - This paper describes a pragmatic approach that can be applied in assessing powder
      blend and unit dosage uniformity of solid dose products at Process Design,
      Process Performance Qualification, and Continued/Ongoing Process Verification
      stages of the Process Validation lifecycle. The statistically based sampling,
      testing, and assessment plan was developed due to the withdrawal of the FDA draft
      guidance for industry "Powder Blends and Finished Dosage Units-Stratified In
      Process Dosage Unit Sampling and Assessment." This paper compares the proposed
      Grouped Area Variance Estimate (GAVE) method with an alternate approach outlining
      the practicality and statistical rationalization using traditional sampling and
      analytical methods. The approach is designed to fit solid dose processes assuring
      high statistical confidence in both powder blend uniformity and dosage unit
      uniformity during all three stages of the lifecycle complying with ASTM standards
      as recommended by the US FDA.

PMID- 29214609
TI  - Soy Protein Microparticles for Enhanced Oral Ibuprofen Delivery: Preparation,
      Characterization, and In Vitro Release Evaluation.
AB  - The objective of this work was to evaluate soy protein isolate (SPI) and acylated
      soy protein (SPA) as spray-drying encapsulation carriers for oral pharmaceutical
      applications. SPI acylation was performed by the Schotten-Baumann reaction. SPA,
      with an acylation rate of 41%, displayed a decrease in solubility in acidic
      conditions, whereas its solubility was unaffected by basic conditions. The drug
      encapsulation capacities of both SPI and SPA were tested with ibuprofen (IBU) as
      a model poorly soluble drug. IBU-SPI and IBU-SPA particles were obtained by spray
      drying under eco-friendly conditions. Yields of 70 to 87% and microencapsulation
      efficiencies exceeding 80% were attained for an IBU content of 20 to 40% w/w,
      confirming the excellent microencapsulation properties of SPI and the suitability
      of the chemical modification. The in vitro release kinetics of IBU were studied
      in simulated gastrointestinal conditions (pH 1.2 and pH 6.8, 37 degrees C). pH
      sensitive release patterns were observed, with an optimized low rate of release
      in simulated gastric fluid for SPA formulations, and a rapid and complete release
      in simulated intestinal fluid for both formulations, due to the optimal pattern
      of pH-dependent solubility for SPA and the molecular dispersion of IBU in soy
      protein. These results demonstrate that SPI and SPA are relevant for the
      development of pH-sensitive drug delivery systems for the oral route.

PMID- 29214610
TI  - Studies on the velocity of blood flow.

PMID- 29214611
TI  - Coronary risk equivalence of diabetes assessed by SPECT-MPI.
AB  - BACKGROUND: Several publications and guidelines designate diabetes mellitus (DM)
      as a coronary artery disease (CAD) risk equivalent. The aim of this investigation
      was to examine DM cardiac risk equivalence from the perspective of stress SPECT
      myocardial perfusion imaging (MPI). METHODS AND RESULTS: We examined
      cardiovascular outcomes (cardiac death or nonfatal MI) of 17,499 patients
      referred for stress SPECT-MPI. Patients were stratified into four categories: non
      DM without CAD, non-DM with CAD, DM without CAD, and DM with CAD, and normal or
      abnormal perfusion. Cardiac events occurred in 872 (5%), with event-free survival
      best among non-DM without CAD, worst in DM with CAD, and intermediate in DM
      without CAD, and non-DM with CAD. After multivariate adjustment, risk remained
      comparable between DM without CAD and non-DM with CAD [AHR 1.0 (95% CI 0.84
      1.28), P =0.74]. Annualized event rates for normal subjects were 1.4% and 1.6%
      for non-DM with CAD and DM without CAD, respectively (P = 0.48) and 3.5% (P =
      0.95) for both abnormal groups. After multivariate adjustment, outcomes were
      comparable within normal [AHR 1.4 (95% CI 0.98-1.96) P = 0.06] and abnormal [AHR
      1.1 (95% CI 0.83-1.50) P = 0.49] MPI. CONCLUSIONS: Diabetic patients without CAD
      have comparable risk of cardiovascular events as non-diabetic patients with CAD
      after stratification by MPI results. These findings support diabetes as a CAD
      equivalent and suggest that MPI provides additional prognostic information in
      such patients.

PMID- 29214612
TI  - Complete revascularization determined by myocardial perfusion imaging could
      improve the outcomes of patients with stable coronary artery disease, compared
      with incomplete revascularization and no revascularization.
AB  - OBJECTIVES: To compare the outcomes among patients treated by complete coronary
      revascularization (CCR) or incomplete coronary revascularization (ICR) and no
      coronary revascularization (NCR) by myocardial perfusion imaging (MPI), as well
      as to evaluate the impact of severity of ischemia on patients with coronary
      artery disease (CAD) by different therapy strategies. BACKGROUND: Using
      myocardial ischemia severity determined by MPI guiding treatment strategies for
      CAD patients still lacks strong clinical evidences. METHODS: Consecutive patients
      (N = 286) underwent clinical stress-rest SPECT MPI and were retrospectively
      followed-up. For assessment of outcome of treatment, all patients were classified
      into three groups (CCR, ICR, and NCR), and further divided into two subgroups as
      mild ischemia (< 10% ischemic myocardium) and moderate-severe ischemia (>= 10%
      ischemic myocardium). All-cause death was defined as the primary endpoint, and
      the composite of deaths, nonfatal myocardial infarction, and repeat
      revascularization (MACE) as the secondary endpoint. RESULTS: Two-hundred eighty
      six patients were followed-up for 46 +/- 21 months. Thirty deaths and 65 MACEs
      were recorded. Patients treated by revascularization had significantly lower MACE
      (P < .001) but not mortality (P = .158) than patients treated by NCR. Outcomes of
      CCR related to mortality rate were greater than ICR and NCR (death: P = .019,
      MACE: P < .001). In patients with moderate-severe ischemia, CCR showed improved
      outcomes than ICR and NCR (death: P = .034; and MACE: P < .001). In patients with
      mild ischemia, the outcomes of CCR, ICR, and NCR had no significant difference (P
      > .05). Multivariate regression Cox analysis revealed that summed difference
      score [death: HR 1.09 (1.03, 1.15), P = .004] was an independent risk factor and
      CCR was an independent negative predictor [death: HR 0.31 (0.12, 0.81), P = .017;
      MACE: HR 0.30 (0.16, 0.57), P < .001]. CONCLUSIONS: Outcomes of patients treated
      by CCR were most likely more promising in comparison with treatment of ICR and
      NCR, especially when patients had over 10% ischemic myocardium.

PMID- 29214613
TI  - Antibiotics in the treatment of patients with lower back pain associated with
      Modic changes: a case series.
AB  - PURPOSE: To determine the clinical effect of antibiotic treatment for patients
      with low back pain and Modic 1 changes. METHODS: This is a retrospective case
      series of patients treated at the Canadian Forces Health Services Centre in
      Ottawa and the McGill University Health Centre. Where available, pain,
      functional, and imaging outcomes in 11 patients treated between 2013 and 2015
      were analyzed to determine effect of antibiotic treatment for patients with low
      back pain and associated Modic 1 changes on magnetic resonance imaging. RESULTS:
      Conservatively, only 3 of 11 patients met the criteria for improvement for pain
      and/or function. While a larger proportion improved in the long term, outcomes
      were not thought to be temporally attributable to antibiotic treatment, as in
      most cases, ongoing therapy, medications, and/or injections were required. There
      did not appear to be a correlation between clinical improvement and associated
      end plate volume involvement for Modic changes. CONCLUSION: Antibiotics for the
      treatment of low back pain in the context of Modic changes on MRI did not
      generally provide significant improvement in pain and function for patients in
      this small cohort. Despite early excitement regarding this treatment, further
      research is required.

PMID- 29214614
TI  - Low rate of early disabling back pain following traumatic or posttraumatic major
      extremity amputation.

PMID- 29214615
TI  - Use of ankle magnetic resonance imaging in the active duty military population:
      the results of a process improvement project.
AB  - BACKGROUND: Preventing overuse of magnetic resonance imaging (MRI) for diagnosing
      ankle pathology was the goal of a process improvement project at a military
      treatment facility. METHODS: Ordering patterns for MRI of nonorthopaedic
      providers and orthopaedic surgeons were evaluated over 2 separate periods. An
      educational initiative on appropriate use of MRI in evaluating ankle complaints
      was conducted between the 2 periods. RESULTS: Between October 2009 and March
      2010, 230 ankle MRIs were performed at our institution, compared to 347 ankle
      MRIs performed between December 2012 and August 2013. A lower number of patients
      underwent operative procedures after the education process than before (17%
      versus 25%). Fellowship-trained foot and ankle surgeons produced the highest
      number of operative patients with their MRI ordering practices (P=.003 and
      P=.0001 for Phases 1 and 2 respectively). There was no change in the number of
      ankle MRI studies ordered each month following the educational initiative (38.3
      and 38.5 for Phases 1 and 2 respectively). CONCLUSIONS: The majority of patients
      undergoing ankle MRI did not undergo operative intervention. Foot and ankle
      surgeons produce the highest number of operative patients with their MRI ordering
      practices. Education alone was ineffective in altering ankle MRI ordering
      patterns.

PMID- 29214616
TI  - A randomized controlled trial evaluating methylsulfonylmethane versus placebo to
      prevent knee pain in military initial entry trainees.
AB  - BACKGROUND: Methylsulfonylmethane (MSM) is a naturally occurring sulfur
      containing substance that has been shown to have anti-inflammatory and
      antioxidative properties. Previous studies using MSM as an oral supplement to
      improve pain in those patients with knee osteoarthritis have shown superiority
      compared to placebo. However, these studies are not translatable to active
      individuals performing high impact activities and have not evaluated MSM as a
      preventative measure. METHODS: A total of 180 subjects ranging in age from 18 to
      40 years were enrolled. Subjects were randomized into 2 groups receiving either 3
      grams OptiMSM methylsulfonylmethane (Bergstrom Nutrition, Vancouver, WA) or a
      placebo for 8 weeks. Outcomes measured were the Knee Osteoarthritis Outcome Score
      (KOOS) and the Profile of Moods States (POMS). RESULTS: Three grams of MSM
      administered daily did not provide significant improvements in the 5 KOOS
      subscales or the 6 POMS subscales at 30 days or 60 days. CONSLUSION: Although 3
      grams of MSM daily can be used safely, there does not appear to be a significant
      improvement in KOOS or POMS.

PMID- 29214617
TI  - GEHS neurophysiological classification system for patients with neuropathy of the
      ulnar nerve at the elbow.
AB  - BACKGROUND: Neuropathy of the ulnar nerve at the elbow is one of a number of
      muscle-related and nerve-related disorders that affect people performing
      intensive work with their hands and upper extremities, and is the second most
      prevalent peripheral nerve mononeuropathy. There are several classification
      systems currently being used by the medical community for patients with
      neuropathy of the ulnar nerve at the elbow. However, few of these classification
      systems include the clinical electrophysiologic parameters nerve conduction (NCS)
      and electromyographic (EMG) studies. PURPOSE: This article describes the GEHS
      (Greathouse, Ernst, Halle, and Shaffer) neurophysiological classification system
      for patients with neuropathy of the ulnar nerve at the elbow and includes 2 case
      studies of patients with electrophysiological evidence of neuropathy of the ulnar
      nerve at the elbow. CASE STUDIES: Two case studies of patients with
      electrophysiological evidence of neuropathy of the ulnar nerve at the elbow are
      presented. The GEHS neurophysiological classification system is incorporated into
      the discussion of these case studies. SUMMARY AND CLINICAL RELEVANCE: This
      article describes the GEHS neurophysiological classification system for patients
      with neuropathy of the ulnar nerve at the elbow which incorporates findings for
      both the NCS and EMG components of the electrophysiological examination.
      Availability of expanded electrophysiological data that includes both NCS and EMG
      testing provides the healthcare team and the patient with more detailed
      information that may be useful in determining next treatment steps as well as
      long-term prognosis. Future research comparing the psychometric properties and
      prognostic utility of the GEHS neurophysiologic classifications is warranted.

PMID- 29214618
TI  - The influence of smoking on recovery from subacromial pain syndrome: a cohort
      from the Military Health System.
AB  - BACKGROUND: Smoking rates are higher in the military population than in the
      civilian sector. Smoking is associated with poor prognosis for many
      musculoskeletal injuries. The purpose of this study was to investigate the
      effects of smoking on recovery from a shoulder injury in a prospective cohort
      seeking care at a military treatment facility. METHODS: Secondary analysis of 98
      patients referred to physical therapy for unilateral shoulder pain. Patients
      received a corticosteroid injection or 6 sessions of physical therapy.
      Sociodemographic and historical variables were analyzed to assess their influence
      on whether a patient achieved the minimally clinically important difference of 12
      or more points on the Shoulder Pain and Disability Index following treatment.
      RESULTS: The mean improvement was almost 50% in both groups and maintained to one
      year. Smoking was associated with not achieving a clinically significant
      improvement in disability scores at 4 weeks, but not 6 months. Higher levels of
      disability at baseline and receiving only the treatment originally assigned (not
      crossing over) were associated with achieving clinically significant changes at
      both 4 weeks and 6 months. COMMENT: Smoking is a modifiable variable that may
      help explain lack of improvement in patients with shoulder pain. Healthcare
      providers in the military setting should keep this in mind when educating this
      patient population and determining their prognosis, especially given high rates
      of smoking. Further research is needed to validate these findings and determine
      their influence on other musculoskeletal injuries.

PMID- 29214619
TI  - Real time interrater reliability of a novel musculoskeletal readiness screening
      tool.
AB  - : Military service members receive regular screenings for a variety of health
      conditions, but a field-expedient and military-specific screening tool that
      identifies an individual's risk for injury has not yet been identified. The
      purpose of this study is to describe the conduct of a novel musculoskeletal
      readiness screening tool (MRST) and evaluate the real-time interrater reliability
      of the MRST when scored by raters with differing levels of medical experience.
      MATERIALS/METHODS: This study included a convenience sample of 40 active duty
      military participants (30 male, 10 female, mean age 29.3+/-6.9 years) without any
      current musculoskeletal injury or pain at the time of enrollment. The MRST
      consisted of 5 physical performance tests and one self-report question as
      follows: (1) weight-bearing lunge (WBL), (2) overhead squat, (3) closed kinetic
      chain upper extremity stability test (CKCUEST), (4) eyes closed forward step
      down, (5) repeated tuck jump, and (6) individual perceived level of risk for MSK
      injury. Three raters (a board certified physical therapist with 15 years of
      experience, a physical therapy student with less than one year didactic training,
      and a physical therapy technician with approximately 10 years of experience)
      independently scored each event as 0, 1, or 2 based on the quality of the
      participant's performance. This scoring system allows for a cumulative score
      ranging from 0 to 12, with lower scores thought to indicate higher risk for
      future injury. Descriptive, reliability, and chance-corrected agreement
      statistics were calculated using IBM SPSS. This study was approved by the Brooke
      Army Medical Center Institutional Review Board at Fort Sam Houston, Texas.
      RESULTS: The mean composite MRST score for all graders was 7.79+/-1.41. Among all
      3 raters the overall reliability was moderate (ICC (2,1)=0.75 (0.62, 0.85)).
      Chance-corrected agreement values for the individual events ranged from slight to
      almost perfect as follows: WBL (kappa=0.33-0.44), overhead squat (kappa=0.57
      0.65), CKCUEST (kappa=0.89-1.0), eyes-closed forward step down (kappa=0.10-0.42),
      repeated tuck jump (kappa=0.39-0.61), individual perceived level of risk for MSK
      injury (kappa=1.0). CONCLUSIONS: The MRST showed moderate interrater reliability
      for the overall composite score with varied levels of agreement for individual
      events scores. Future research should investigate test-retest reliability and
      interrater reliability among medical personnel from different disciplines.

PMID- 29214620
TI  - Cognitive behavioral therapy for insomnia treatment in a military deployed
      operational setting utilizing enlisted combat medics: a Quality and Process
      Improvement Project.
AB  - Insomnia disorder is a prevalent condition especially among the American
      military, affecting up to 50% of service members. It is shown to affect military
      performance. Guidelines recommend the use of nonpharmacologic approaches as
      initial treatment of insomnia. Cognitive behavioral therapy informed insomnia
      treatment (CBT-I) has the greatest evidence, however it requires specialized
      training. While deployed in the Middle East in support of US military operations,
      we faced a resource challenge while caring for service members with insomnia. In
      order to meet the needs of the population, we created a checklist based CBT-I
      informed treatment to enable our health extenders, including combat medics and
      behavioral health specialists. Following institutional review board determination
      of this project as nonresearch, we implemented this as a Quality
      Improvement/Process Improvement Project (QI/PI). Here we describe the 4 phases of
      this QI/PI and our outcomes. This process can be easily reproduced in either the
      deployed or garrison setting with minimum efforts and resources, enabling
      delivery of high quality, evidence-and guidelines-based treatment while using
      combat medics and behavioral health specialists to their maximum potential.

PMID- 29214621
TI  - Sandfly fever in Afghanistan-a sometimes overlooked disease of military
      importance: a case series and review of the literature.
AB  - Sandfly fever, sometimes known as pappataci fever or Phlebotomus fever, is a
      vector transmitted viral illness with a history of affecting naive military
      formations that travel through or fight in areas in which the infection is
      endemic. We present a series of 4 hospitalized cases of sandfly fever (2
      presumptive, 2 laboratory confirmed) that were admitted to a Role 3 hospital in
      Afghanistan for evaluation and treatment following medical evacuation from a
      forward area for marked fevers and malaise. Laboratory evaluation of these cases
      was significant for leukopenia and thrombocytopenia, consistent with historical
      descriptions of sandfly fever. In the correct geographic and clinical setting,
      the finding of mild leukopenia among a cluster of febrile patients should prompt
      the clinician to at least consider a diagnosis of sandfly fever. A cluster
      investigation conducted by preventive medicine personnel identified numerous
      other presumed cases of sandfly fever in this forward special operations camp.
      Response efforts emphasized enforcement of standard vector-borne disease control
      measures by operational leadership in order to limit effect on tactical
      operations. We review historical instances of sandfly fever affecting military
      operations, and present a review of clinical presentation, transmission,
      management, and prevention.

PMID- 29214622
TI  - Smoking and periodontal disease.

PMID- 29214623
TI  - Core temperature responses of military working dogs during training activities
      and exercise walks.
AB  - Heat strain is common in military working dogs (MWDs), but can be mitigated by
      limiting duration of activity to avoid overheating and allowing sufficient time
      for recovery. To determine work/rest times for MWDs, temperature responses during
      training must be characterized. This study measured body core temperature of 48
      MWDs at Lackland Air Force Base, San Antonio, TX. Twenty-four MWDs in training
      for patrol and detection activities participated under a range of ambient
      temperatures in August (27 degrees C-32 degrees C), October (22 degrees C-26
      degrees C) and March (approximately 13 degrees C). These MWDs swallowed a
      telemetric thermometer pill to measure continuous gastrointestinal tract
      temperature (Tgi). Twenty-four kennel MWDs participated in July (25 degrees C-29
      degrees C). In these dogs rectal temperature (Tre) was measured manually during a
      standard exercise walk. For the MWDs in training, Tgi before the first activity
      was 38.5+/-0.5 degrees C (mean+/-SD) and final Tgi was 39.8+/-0.6 degrees C after
      sessions that lasted 13.1+/-4.9 minutes (5.4 to 26.3 minutes). Peak Tgi, 0.4+/
      0.4 degrees C above final Tgi, occurred 8 to 12 minutes into recovery. Before
      beginning a second activity 40 to 165 minutes later, Tgi was within 0.5 degrees C
      of initial values for 80% of dogs. For the kennel MWDs, Tre was 39.0+/-0.8
      degrees C (37.7 degrees C to 40.7 degrees C) at the start and 40.1+/-0.6 degrees
      C at the end of the 21.3+/-2.8 minute walk. The continuous increase in core
      temperature during activity of both groups of MWDs indicates that limiting
      exercise duration is important for minimizing risk of overheating in MWDs. The
      observation of continued increase in Tgi to a peak after exercise ends suggests
      that for MWDs suspected of overheating temperature should be monitored for at
      least 15 minutes postexercise to ensure recovery.

PMID- 29214624
TI  - Effects of technique-focused training in conjunction with physical readiness
      training on Army physical fitness test performance.
AB  - The Army Physical Fitness Test (APFT) is a semiannual requirement. While
      conducting physical readiness training (PRT) is a requirement for all Soldiers,
      there is no requirement to train Soldiers on techniques that may help to optimize
      their performance on the APFT. A cohort of 34 officers that attended the Army
      Medical Department Basic Officer Leadership Course completed a technique-focused
      training program in conjunction with their required PRT program subsequent to
      failing one or more events on their initial APFT. The training consisted of a 30
      minute video lesson and an individualized performance assessment completed by an
      Army physical therapist. Upon retest 10 days after the initial test, 27 (79.4%)
      participants passed the APFT with a mean improvement of 22.3 points on their
      overall APFT score. When evaluating change in performance by event based on
      failing the event initially, the observed improvement was an increase of over 9
      push-ups, over 11 sit-ups, and nearly 2 minutes on the run event. The addition of
      a technique-focused training program to an existing PRT program can result in
      significant short-term improvement for those with substandard APFT performance.

PMID- 29214625
TI  - Evidence-based practice and single-case designs in psychotherapy.

PMID- 29214626
TI  - A descriptive analysis of data from the Department of Defense Joint Trauma System
      Prehospital Trauma Registry.
AB  - : The active battlefield is an environment of chaos and confusion. Depending on
      the scale of combat, the chaos and confusion often extend into the prehospital
      combat setting with multiple personnel and units involved in the chain of care of
      casualties. The chaos of the prehospital combat setting has led to limitations in
      the availability of data for performance improvement and research. The Department
      of Defense (DoD) Joint Trauma System (JTS) Prehospital Trauma Registry (PHTR) was
      developed in conjunction with the updated Tactical Combat Casualty Care (TCCC)
      card and a TCCC after action report (AAR), and currently serves as the
      prehospital repository and module of the DoD Trauma Registry (DoDTR). We
      conducted a descriptive analysis of data from the DoDTR PHTR. METHODS: The JTS
      collected trauma-associated data which comprise the PHTR are consolidated from
      TCCC cards and TCCC AARs. Where possible (requires 2 patient identifiers), JTS
      linked data from the PHTR module to other modules in the DoDTR to maximize
      availability of prehospital data and gain additional information regarding
      clinical outcomes. RESULTS: From January 2013 through September 2014, there were
      705 patients available for research, of which 94.8% (668/705) had data from TCCC
      AARs, 3.3% (23/705) had data from TCCC cards, and 2.0% (14/705) had data
      available from DoDTR collection forms. There were one or more of the following
      data points per subject: pulse rate (77.4%, n=546), blood pressure (75.9%,
      n=535), respiratory rate (76.5%, n=539), pulse oximetry (61.8%, n=436), mental
      status (96.0%, n=677) and pain score (24.5%, n=173). Only 42.4% (647/1,527) of
      vital sign metrics had an associated time stamp. Documented interventions
      included limb tourniquets, of which only 27.3% (113/414) had an associated
      documentation of application time. Only 27.0% (190/705) of patients in the PHTR
      could be linked to the DoDTR due to missing identifiers. CONCLUSIONS: The PHTR
      data capture was suboptimal with many patients lacking documentation of vital
      signs and procedural details. Future efforts to improve prehospital data capture
      will require ownership and enforcement by unit leadership.

PMID- 29214627
TI  - A 12-month descriptive analysis of emergency intubations at Brooke Army Medical
      Center: a National Emergency Airway Registry study.
AB  - : Emergency airway management is a critical skill for military healthcare
      providers. Our goal was to describe the Emergency Department (ED) intubations at
      Brooke Army Medical Center (BAMC) over a 12-month period. MATERIAL AND METHODS:
      Physicians performing endotracheal intubations in the BAMC ED complete data
      collection forms for each intubation event as part of the National Emergency
      Airway Registry, including patient demographics, intubation techniques, success
      and failure rates, adverse events, and patient disposition. We cross-referenced
      these forms against the numbers of intubation events reported in the ED nursing
      daily reports to ensure capture of all intubations. Providers completed forms for
      every intubation within 6 weeks of the procedure. We analyzed data from March 28,
      2016, to March 27, 2017. RESULTS: During the study period, providers performed
      259 intubations in the BAMC ED. Reasons for intubation were related to trauma for
      184 patients (71.0%) and medical conditions for 75 patients (29.0%). Overall,
      first-attempt success was 83.0%. Emergency medicine residents performed a
      majority of first attempts (95.0%). Most common devices chosen on first attempt
      were a video laryngoscope for 143 patients (55.2%) and a direct laryngoscope for
      115 patients (44.4%). One patient underwent cricothyrotomy. The 2 most common
      induction agents were ketamine (59.8%; 95% CI, 55.2%-67.4%) and etomidate (19.3%;
      95% CI, 14.7%-24.7%). The most common neuromuscular blocking agents were
      rocuronium (62.9%; 95% CI, 56.7%-68.8%) and succinylcholine (18.9%; 95% CI, 14.3%
      24.2%). CONCLUSION: In the BAMC ED, emergency intubation most commonly occurred
      for trauma indications using video laryngoscopy with a high first-pass success.

PMID- 29214628
TI  - An evaluation of the significance of individual endogenous risk factors and
      medical and orthopaedic conditions on physical fitness in military executives.
AB  - As part of occupational health promotion in the Bundeswehr (military services of
      the Federal Republic of Germany), top-ranking executives were offered a medical
      examination and training program. The participants were subjected to
      retrospective evaluation. The aim of this study was to determine to what extent
      risk factors for the development of internal and orthopaedic conditions are
      present in military executives and how these factors affect physical fitness. To
      collect their medical history, a total of 122 male subjects answered a
      questionnaire aimed at evaluating private and occupational stress factors. This
      process was followed by an internal and orthopaedic examination. A lactate
      performance test (treadmill or bicycle ergometry) was conducted. The results
      showed that the presence of hypertension correlates with reduced fitness. While
      orthopaedic conditions had no negative influence on executives' fitness, high
      body mass index and waist circumference, mental stress, and older age did. It is
      recommended that executives undergo professionally guided endurance and weight
      training on a regular basis in order to prevent the development of internal and
      orthopaedic conditions.

PMID- 29214629
TI  - Targeting early PKCtheta-dependent T-cell infiltration of dystrophic muscle
      reduces disease severity in a mouse model of muscular dystrophy.
AB  - Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy
      and contributes to muscle fibre injury and disease progression. Although previous
      studies have implicated T cells in the development of muscle fibrosis, little is
      known about their role during the early stages of muscular dystrophy. Here, we
      show that T cells are among the first cells to infiltrate mdx mouse dystrophic
      muscle, prior to the onset of necrosis, suggesting an important role in early
      disease pathogenesis. Based on our comprehensive analysis of the kinetics of the
      immune response, we further identify the early pre-necrotic stage of muscular
      dystrophy as the relevant time frame for T-cell-based interventions. We focused
      on protein kinase C theta (PKCtheta, encoded by Prkcq), a critical regulator of
      effector T-cell activation, as a potential target to inhibit T-cell activity in
      dystrophic muscle. Lack of PKCtheta not only reduced the frequency and number of
      infiltrating T cells but also led to quantitative and qualitative changes in the
      innate immune cell infiltrate in mdx/Prkcq-/- muscle. These changes were due to
      the inhibition of T cells, since PKCtheta was necessary for T-cell but not for
      myeloid cell infiltration of acutely injured muscle. Targeting T cells with a
      PKCtheta inhibitor early in the disease process markedly diminished the size of
      the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover,
      diaphragm necrosis and fibrosis were also reduced following treatment. Overall,
      our findings identify the early T-cell infiltrate as a therapeutic target and
      highlight the potential of PKCtheta inhibition as a therapeutic approach to
      muscular dystrophy. Copyright (c) 2017 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29214630
TI  - A DEL phenotype attributed to RHD Exon 9 sequence deletion: slipped-strand
      mispairing and blood group polymorphisms.
AB  - BACKGROUND: The RhD blood group antigen is extremely polymorphic and the DEL
      phenotype represents one such class of polymorphisms. The DEL phenotype prevalent
      in East Asian populations arises from a synonymous substitution defined as
      RHD*1227A. However, initially, based on genomic and cDNA studies, the genetic
      basis for a DEL phenotype in Taiwan was attributed to a deletion of RHD Exon 9
      that was never verified at the genomic level by any other independent group. Here
      we investigate the genetic basis for a Caucasian donor with a DEL partial D
      phenotype and compare the genomic findings to those initial molecular studies.
      STUDY DESIGN AND METHODS: The 3'-region of the RHD gene was amplified by long
      range polymerase chain reaction (PCR) for massively parallel sequencing. Primers
      were designed to encompass a deletion, flanking Exon 9, by standard PCR for
      Sanger sequencing. Targeted sequencing of exons and flanking introns was also
      performed. RESULTS: Genomic DNA exhibited a 1012-bp deletion spanning from Intron
      8, across Exon 9 into Intron 9. The deletion breakpoints occurred between two 25
      bp repeat motifs flanking Exon 9 such that one repeat sequence remained.
      CONCLUSION: Deletion mutations bordered by repeat sequences are a hallmark of
      slipped-strand mispairing (SSM) event. We propose this genetic mechanism
      generated the germline deletion in the Caucasian donor. Extensive studies show
      that the RHD*1227A is the most prevalent DEL allele in East Asian populations and
      may have confounded the initial molecular studies. Review of the literature
      revealed that the SSM model explains some of the extreme polymorphisms observed
      in the clinically significant RhD blood group antigen.

PMID- 29214631
TI  - System matrix computation vs storage on GPU: A comparative study in cone beam CT.
AB  - PURPOSE: Iterative reconstruction algorithms in computed tomography (CT) require
      a fast method for computing the intersection distances between the trajectories
      of photons and the object, also called ray tracing or system matrix computation.
      This work focused on the thin-ray model is aimed at comparing different system
      matrix handling strategies using graphical processing units (GPUs). METHODS: In
      this work, the system matrix is modeled by thin rays intersecting a regular grid
      of box-shaped voxels, known to be an accurate representation of the forward
      projection operator in CT. However, an uncompressed system matrix exceeds the
      random access memory (RAM) capacities of typical computers by one order of
      magnitude or more. Considering the RAM limitations of GPU hardware, several
      system matrix handling methods were compared: full storage of a compressed system
      matrix, on-the-fly computation of its coefficients, and partial storage of the
      system matrix with partial on-the-fly computation. These methods were tested on
      geometries mimicking a cone beam CT (CBCT) acquisition of a human head. Execution
      times of three routines of interest were compared: forward projection,
      backprojection, and ordered-subsets convex (OSC) iteration. RESULTS: A fully
      stored system matrix yielded the shortest backprojection and OSC iteration times,
      with a 1.52* acceleration for OSC when compared to the on-the-fly approach.
      Nevertheless, the maximum problem size was bound by the available GPU RAM and
      geometrical symmetries. On-the-fly coefficient computation did not require
      symmetries and was shown to be the fastest for forward projection. It also
      offered reasonable execution times of about 176.4 ms per view per OSC iteration
      for a detector of 512 * 448 pixels and a volume of 3843 voxels, using commodity
      GPU hardware. Partial system matrix storage has shown a performance similar to
      the on-the-fly approach, while still relying on symmetries. CONCLUSION: Partial
      system matrix storage was shown to yield the lowest relative performance. On-the
      fly ray tracing was shown to be the most flexible method, yielding reasonable
      execution times. A fully stored system matrix allowed for the lowest
      backprojection and OSC iteration times and may be of interest for certain
      performance-oriented applications.

PMID- 29214632
TI  - Thorough analysis of unorthodox ABO deletions called by the 1000 Genomes project.
AB  - BACKGROUND AND OBJECTIVES: ABO remains the clinically most important blood group
      system, but despite earlier extensive research, significant findings are still
      being made. The vast majority of catalogued ABO null alleles are based on the
      c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are
      rare. While analysing the data set from the 1000 Genomes (1000G) project, we
      encountered two previously uncharacterized deletions, which needed further
      exploration. MATERIALS AND METHODS: The Erythrogene database, complemented with
      bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G.
      DNA samples from selected 1000G donors and African blood donors were examined by
      allele-specific PCR and Sanger sequencing to characterize predicted deletions.
      RESULTS: A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G
      individuals, predominantly Africans. This allele was confirmed and its exact
      deletion point defined by bioinformatic analyses and in vitro experiments. A PCR
      assay was developed, and screening of African samples revealed three donors
      heterozygous for this deletion, which was thereby phenotypically established as
      an O allele. Analysis of upstream genetic markers indicated an ancestral origin
      from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism
      behind O alleles. A 24-bp deletion was called in nine individuals and showed
      greater diversity regarding ethnic distribution and allelic background. It could
      neither be confirmed by in silico nor in vitro experiments. CONCLUSION: A
      previously uncharacterized ABO deletion among Africans was comprehensively mapped
      and a genotyping strategy devised. The false prediction of another deletion
      emphasizes the need for cautious interpretation of NGS data and calls for strict
      validation routines.

PMID- 29214633
TI  - Placenta accreta spectrum disorder trends in the context of the universal two
      child policy in China and the risk of hysterectomy.
AB  - OBJECTIVE: To identify both the trends in placenta accreta spectrum (PAS)
      disorders in the context of the universal two-child policy in China and risk
      factors for hysterectomy. METHODS: The present retrospective analysis included
      confirmed PAS disorders during cesarean delivery at a tertiary hospital in
      Changsha, Hunan, China, from January 1, 2007, to December 31, 2016. Multivariable
      logistic regression was used to estimate the risk of hysterectomy. RESULTS:
      During the 10-year study period, the overall incidence of cesarean delivery was
      51.6% (13 530/26 214) and that of PAS disorders was 1.2% (302/26 214). The PAS
      rate increased from 0.1% (5/4617) in 2007-2008 to 2.1% (133/6351) in 2015-2016,
      alongside a rise in elective repeat cesarean delivery from 5.0% (106/2124) to
      38.4% (1385/3603). Previous cesarean delivery greatly increased the likelihood of
      PAS disorders (odds ratio [OR] 97.4; P<0.001). Invasive depth (OR 92.0; P<0.001),
      inter-cesarean interval less than 36 months (OR 7.0; P=0.002), rural residence
      (OR 5.3; P=0.018), and advanced maternal age (OR 3.0; P=0.045) were independent
      risk factors for hysterectomy among women with PAS disorders. CONCLUSION: The
      increasing incidence of elective repeat cesarean delivery combined with a high
      overall rate of cesarean delivery implies a high prevalence of PAS disorders
      within the context of the universal two-child policy in China. The main predictor
      of hysterectomy was invasive depth.

PMID- 29214634
TI  - A case of hypoglossal nerve stimulator-resistant obstructive sleep apnea cured
      with the addition of a chin strap.
AB  - A population of appropriately selected patients does not respond, or does not
      achieve cure, with hypoglossal nerve stimulation (HGNS). We describe the case of
      nonresponder whose obstructive sleep apnea (OSA) resolved with the addition of
      chin strap. After initial placement and titration of HGNS implant, follow-up
      sleep study demonstrated persistent moderate OSA. Drug-induced sleep endoscopy
      demonstrated supraglottic collapse with activate neurostimulation. With mouth
      closure and change of stimulation settings to unipolar from bipolar, the airway
      collapse and desaturations improved. The follow-up polysomnogram with (HGNS)
      therapy and chin strap demonstrated resolution of sleep apnea. Laryngoscope,
      128:1727-1729, 2018.

PMID- 29214635
TI  - Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin
      neurons.
AB  - KEY POINTS: Neurons in the hypothalamus of the brain which secrete the peptide
      kisspeptin are important regulators of reproduction, and normal reproductive
      development. Electrical activity, in the form of action potentials, or spikes,
      leads to secretion of peptides and neurotransmitters, influencing the activity of
      downstream neurons; in kisspeptin neurons, this activity is highly irregular, but
      the mechanism of this is not known. In this study, we show that irregularity
      depends on the presence of a particular type of potassium ion channel in the
      membrane, which opens transiently in response to electrical excitation. The
      results contribute to understanding how kisspeptin neurons generate and time
      their membrane potential spikes, and how reliable this process is. Improved
      understanding of the activity of kisspeptin neurons, and how it shapes their
      secretion of peptides, is expected to lead to better treatment for reproductive
      dysfunction and disorders of reproductive development. ABSTRACT: Kisspeptin
      neurons in the hypothalamus are critically involved in reproductive function, via
      their effect on GnRH neuron activity and consequent gonadotropin release.
      Kisspeptin neurons show an intrinsic irregularity of firing, but the mechanism of
      this remains unclear. To address this, we carried out targeted whole-cell patch
      clamp recordings of kisspeptin neurons in the arcuate nucleus (Kiss1Arc ), in
      brain slices isolated from adult male Kiss-Cre:tdTomato mice. Cells fired
      irregularly in response to constant current stimuli, with a wide range of spike
      time variability, and prominent subthreshold voltage fluctuations. In voltage
      clamp, both a persistent sodium (NaP) current and a fast transient (A-type)
      potassium current were apparent, activating at potentials just below the
      threshold for spiking. These currents have also previously been described in
      irregular-spiking cortical interneurons, in which the A-type current, mediated by
      Kv4 channels, interacts with NaP current to generate complex dynamics of the
      membrane potential, and irregular firing. In Kiss1Arc neurons, A-type current was
      blocked by phrixotoxin, a specific blocker of Kv4.2/4.3 channels, and consistent
      expression of Kv4.2 transcripts was detected by single-cell RT-PCR. In addition,
      firing irregularity was correlated to the density of A-type current in the
      membrane. Using conductance injection, we demonstrated that adding Kv4-like
      potassium conductance (gKv4 ) to a cell produces a striking increase in firing
      irregularity, and excitability is reduced, while subtracting gKv4 has the
      opposite effects. Thus, we propose that Kv4 interacting dynamically with NaP is a
      key determinant of the irregular firing behaviour of Kiss1Arc neurons, shaping
      their physiological function in gonadotropin release.

PMID- 29214636
TI  - Evolution of microRNA827 targeting in the plant kingdom.
AB  - Unlike most ancient microRNAs, which conservatively target homologous genes
      across species, microRNA827 (miR827) targets two different types of SPX
      (SYG1/PHO81/XPR1)-domain-containing genes, NITROGEN LIMITATION ADAPTATION (NLA)
      and PHOSPHATE TRANSPORTER 5 (PHT5), in Arabidopsis thaliana and Oryza sativa to
      regulate phosphate (Pi) transport and storage, respectively. However, how miR827
      shifted its target preference and its evolutionary history are unknown. Based on
      target prediction analysis, we found that in most angiosperms, miR827
      conservatively targets PHT5 homologs, but in Brassicaceae and Cleomaceae it
      preferentially targets NLA homologs, and we provide evidence for the transition
      of target preference during Brassicales evolution. Intriguingly, we found a
      lineage-specific loss of the miR827-regulatory module in legumes. Analysis of
      miR827-mediated cleavage efficiency and the expression of PHT5 in A. thaliana
      indicated that accumulation of mutations in the target site and the exclusion of
      the target site by alternative transcriptional initiation eliminated PHT5
      targeting by miR827. Here, we identified a transition of miR827 target preference
      during plant evolution and revealed the uniqueness of miR827-mediated regulation
      among conserved plant miRNAs. Despite the change in its target preference,
      upregulation of miR827 by Pi starvation and its role in regulating cellular Pi
      homeostasis were retained.

PMID- 29214637
TI  - Identification and treatment of gestational trophoblastic neoplasia located in
      the cesarean scar.
AB  - OBJECTIVE: To identify the clinical characteristics of, and the diagnostic and
      therapeutic strategies for, gestational trophoblastic neoplasia (GTN) located in
      the cesarean scar. METHODS: The present retrospective analysis was conducted
      among patients diagnosed with GTN located in the cesarean scar at Peking Union
      Medical College Hospital, Beijing, China, between June 1, 2006, and May 31, 2016.
      Clinical features, diagnostic and therapeutic procedures, and outcomes were
      reviewed. RESULTS: Of 938 women diagnosed with GTN, 31 (3.3%) patients had GTN
      located in the cesarean scar. Irregular vaginal bleeding was the main clinical
      manifestation. Twenty (65%) patients received an accurate diagnosis based on a
      history of molar pregnancy/a high beta-human chorionic gonadotropin level/typical
      imaging presentations. The remaining 11 patients were initially misdiagnosed; the
      definitive diagnosis was made by pathology. All patients received chemotherapy;
      22 (71%) women also underwent hysterectomy or localized uterine lesion resection
      because of chemoresistant lesions. All patients had a complete remission; at a
      median follow-up of 35 months, only 1 (3%) woman had a relapse. CONCLUSION: Owing
      to its rarity and nonspecific symptoms, GTN located in the cesarean scar is prone
      to misdiagnosis. In patients without typical manifestations, the definitive
      diagnosis often relies on pathology. For treatment, uterine lesion resection is a
      useful adjunct to chemotherapy.

PMID- 29214638
TI  - Harnessing the Power of Real-World Evidence (RWE): A Checklist to Ensure
      Regulatory-Grade Data Quality.
AB  - The role of real-world evidence (RWE) in regulatory, drug development, and
      healthcare decision-making is rapidly expanding. Recent advances have increased
      the complexity of cancer care and widened the gap between randomized clinical
      trial (RCT) results and the evidence needed for real-world clinical decisions.
      Instead of remaining invisible, data from the >95% of cancer patients treated
      outside of clinical trials can help fill this void.

PMID- 29214639
TI  - Cannabinoids for epilepsy: What do we know and where do we go?
AB  - Over the past decade there has been an increasing interest in using cannabinoids
      to treat a range of epilepsy syndromes following reports of some remarkable
      responses in individual patients. The situation is complicated by the fact that
      these agents do not appear to work via their attachment to endogenous cannabinoid
      receptors. Their pharmacokinetics are complex, and bioavailability is variable,
      resulting in difficulty in developing a suitable formulation for oral delivery.
      Drug interactions also represent another complication in their everyday use.
      Nevertheless, recent randomized, placebo-controlled trials with cannabidiol
      support its efficacy in Dravet and Lennox-Gastaut syndromes. Further placebo
      controlled studies are underway in adults with focal epilepsy using
      cannabidivarin. The many unanswered questions in the use of cannabinoids to treat
      epileptic seizures are briefly summarized in the conclusion.

PMID- 29214640
TI  - Management of head and neck primary unknown squamous cell carcinoma using
      combined positron emission tomography-computed tomography and transoral laser
      microsurgery.
AB  - OBJECTIVES/HYPOTHESIS: The unknown primary of the neck is commonly encountered by
      the head and neck surgeon. Despite the exhaustive diagnostic tools employed in
      traditional detection protocols, many unknown primaries are not found, and the
      patient is subjected to wide-field radiation and chemotherapy during treatment.
      Localizing the primary tumor has demonstrated therapeutic benefits, improved
      quality of life, and overall survival. The authors' objective was to determine
      the efficacy of a new management protocol for unknown primaries of the head and
      neck. STUDY DESIGN: Prospective cohort study. METHODS: Our technique involved a
      preoperative positron emission tomography-computed tomography (PET-CT) followed
      by a planned transoral laser microsurgery (TLM) approach. Efficacy was assessed
      based on survival statistics, disease control, detection rates, the proportion of
      patients not receiving adjuvant therapy, and the proportion of PET-CT scans
      helpful for detection of the primary cancer. RESULTS: The occult primary was
      located in 25 of the 27 patients (93%), with the majority found in the palatine
      tonsil (52%). Both overall survival and disease-specific survival was 80% at 36
      months. Local control was achieved in 100% of patients. After surgery, 37.0% (n =
      10) received adjuvant radiation alone and 33.3% (n = 9) of patients went on to
      receive adjuvant chemoradiation. On imaging, 72% (n = 18) of PET-CT scans
      correctly localized the primary tumor. CONCLUSIONS: Occult head and neck
      primaries present a diagnostic challenge that is not adequately overcome using
      traditional detection protocols. The current study presents our unique protocol
      at Dalhousie University, which demonstrates the efficacy of the PET-CT TLM
      protocol from both a detection and therapeutic perspective. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 128:2307-2311, 2018.

PMID- 29214641
TI  - An app to enhance resident education in otolaryngology.
AB  - OBJECTIVE: Technological change is leading to an evolution in medical education.
      The objective of our study was to assess the impact of a medical knowledge app,
      called PulseQD, on resident education within our otolaryngology-head and neck
      surgery department at Montefiore Medical Center, Albert Einstein College of
      Medicine (Bronx, NY). METHODS: A prospective cohort study was conducted within
      the Department of Otolaryngology-Head and Neck Surgery from July 2016 to June
      2017. All faculty attendings and residents were asked to participate in the study
      and were included. A Web and mobile-based app, PulseQD, that allowed for
      collaborative learning was implemented. Questionnaires were given at the
      beginning and end of the academic year. Otolaryngology Training Exam (OTE) scores
      were collected RESULTS: A total of 20 residents and 13 faculty members
      participated in the study. Residents used online sources of medical information
      significantly more often than faculty (90% and 54%, respectively, P = 0.0179).
      Residents and faculty felt that PulseQD offered a valuable perspective on
      clinically relevant medical information (P = 0.0003), was a great way to test
      clinical and medical knowledge (P = 0.0001), and improved the sharing and
      discussing of medical knowledge (P < 0.0001). There was a statistically
      significant 5.8% improvement in OTE scores (P = 0.0008) at the end of the
      academic year. CONCLUSION: The implementation of a novel mobile app, PulseQD, was
      well received by residents and faculty in the Department of Otolaryngology-Head
      and Neck Surgery. Preliminary data suggest that app-based learning may lead to
      improved performance on knowledge-based assessments. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 128:1340-1345, 2018.

PMID- 29214642
TI  - Allergic contact dermatitis caused by topical herbal remedies: importance of
      patch testing with the patients' own products.
AB  - BACKGROUND: Natural ingredients have variable compositions, so their allergenic
      potencies may differ. OBJECTIVES: To retrospectively analyse subjects reacting to
      herbal remedies over the past 27 years, with the aim of (i) evaluating
      demographic characteristics and lesion locations, (ii) describing the frequencies
      of positive patch test reactions, (iii) identifing sensitization sources, and
      (iv) studying concomitant sensitivity. PATIENTS AND METHODS: In total, 15980
      patients were patch tested between 1990 and 2016 with the European baseline
      series and/or other series, product(s) used, and, whenever possible, the
      respective ingredients. RESULTS: Altogether, 8942 (56%) of 15 980 patients
      presented with at least one positive reaction. Reactions to topical herbal
      medicines, most often applied to treat an eczematous condition, leg ulcers, or
      other wounds, were seen in 125 (0.8%), that is, 1.4% of the contact-allergic
      subjects. Hands, legs and feet were the most frequently affected body sites.
      Twenty-one botanical allergens were identified, the commonest being Myroxylon
      pereirae (balsam of Peru), Compositae plants, and tincture of benzoin. Many
      patients presented with multiple positive test reactions, and some did not react
      to the commercial allergens but only to the products used. CONCLUSIONS: Topical
      herbal remedies should not be applied on damaged skin, as multiple sensitization
      may develop. Moreover, patch testing with the culprit products is important for
      the diagnosis.

PMID- 29214643
TI  - Trends in serum human chorionic gonadotropin levels 0-4 days after methotrexate
      administration for predicting tubal ectopic pregnancy treatment success.
AB  - OBJECTIVE: To evaluate serum human chorionic gonadotropin (HCG) levels 0-4 days
      after single-dose methotrexate administration for tubal ectopic pregnancy.
      METHODS: The present retrospective study included women with tubal ectopic
      pregnancy treated by methotrexate at a tertiary hospital in Hong Kong, China,
      between January 1, 2007, and December 31, 2016. Patients were stratified serum
      HCG levels rose or fell from day 0-4 post-administration. Trends in day 0-4 serum
      HCG to predict treatment success were compared with that of day 4-7 serum HCG.
      The optimal drop in HCG was identified by receiver operating characteristic curve
      analysis. RESULTS: There were 102 patients included. The positive predictive
      value (PPV) of day 0-4 serum HCG for treatment success was 91% (95% confidence
      interval [CI] 82-96), which is comparable to the current criterion of a 15% drop
      in day 4-7 serum HCG (PPV 91%, 95% CI 84-95). A 6% drop in day 0-4 serum HCG was
      the best predictor of treatment success (PPV 96%, 95% CI 86-99). CONCLUSION: A
      drop in day 0-4 serum HCG provided earlier prognostic information and was not
      inferior to the current criterion.

PMID- 29214644
TI  - Acute oxygen sensing by the carotid body: a rattlebag of molecular mechanisms.
AB  - The molecular underpinnings of the oxygen sensitivity of the carotid body Type I
      cells are becoming better defined as research begins to identify potential
      interactions between previously separate theories. Nevertheless, the field of
      oxygen chemoreception still presents the general observer with a bewildering
      array of potential signalling pathways by which a fall in oxygen levels might
      initiate Type I cell activation. The purpose of this brief review is to address
      five of the current oxygen sensing hypotheses: the lactate-Olfr 78 hypothesis of
      oxygen chemotransduction; the role mitochondrial ATP and metabolism may have in
      chemotransduction; the AMP-activated protein kinase hypothesis and its current
      role in oxygen sensing by the carotid body; reactive oxygen species as key
      transducers in the oxygen sensing cascade; and the mechanisms by which H2 S,
      reactive oxygen species and haem oxygenase may integrate to provide a rapid
      oxygen sensing transduction system. Over the previous 15 years several lines of
      research into acute hypoxic chemotransduction mechanisms have focused on the
      integration of mitochondrial and membrane signalling. This review places an
      emphasis on the subplasmalemmal-mitochondrial microenvironment in Type I cells
      and how theories of acute oxygen sensing are increasingly dependent on functional
      interaction within this microenvironment.

PMID- 29214645
TI  - Recovery characteristics of patients receiving either sugammadex or neostigmine
      and glycopyrrolate for reversal of neuromuscular block: a randomised controlled
      trial.
AB  - Sugammadex more rapidly and reliably reverses rocuronium-induced neuromuscular
      block compared with neostigmine, but it is not known if subsequent patient
      outcomes, including nausea, vomiting and other aspects of recovery are modified.
      In this study, we compared the recovery characteristics of sugammadex and
      neostigmine/glycopyrrolate following reversal of neuromuscular block. This was a
      single-centre, randomised, blinded, parallel-group clinical trial in women
      undergoing elective day-surgical laparoscopic gynaecological surgery, with a
      standardised general anaesthesia regimen that included rocuronium. Neuromuscular
      block was reversed with either sugammadex 2 mg.kg-1 or neostigmine 40 MUg.kg-1
      and glycopyrrolate 400 MUg. The primary outcome was the incidence of nausea and
      vomiting during the first six postoperative hours. Secondary outcomes included
      other measures of postoperative recovery such as patient symptoms and recovery
      scores. Three-hundred and four women were analysed by intention-to-treat
      (sugammadex n = 151, neostigmine n = 153), which included four major protocol
      violations. There was no significant difference between sugammadex and
      neostigmine groups in the incidence of early nausea and vomiting (49.0% vs.
      51.0%, respectively; OR 0.92, 95%CI 0.59-1.45; p = 0.731). Double vision (11.5%
      vs. 20.0%; p = 0.044) and dry mouth (71.6% vs. 85.5%; p = 0.003) were less common
      after sugammadex. Sedation scores at 2 h were also lower after sugammadex (median
      (IQR [range]) 0 (0-3 [0-10]) vs. 2 (0-4.[0-10]); p = 0.021). Twenty-four-hour
      recovery scores were not significantly different between groups. Reversal with
      sugammadex in this patient population did not reduce postoperative nausea or
      vomiting compared with neostigmine/glycopyrrolate.

PMID- 29214646
TI  - Endoscopic sentinel lymph node biopsy using indocyanine green-neomannosyl human
      serum albumin.
AB  - OBJECTIVE: The aim of this study was to determine the possibility of endoscopic
      sentinel lymph node biopsy of the head and neck region using indocyanine green
      neomannosyl human serum albumin (ICG:MSA) and a custom-made intraoperative color
      and-fluorescence-merged imaging system (ICFIS). METHODS: Using mouse and rabbit
      models of tongue cancer, we performed sentinel lymph node biopsy using an ICG:MSA
      tracer and custom imaging system equipped with an endoscope. RESULTS: ICG:MSA was
      localized to the cervical lymph node on the ipsilateral side for up to 30 minutes
      compared to ICG tracer (ICG n = 3, IGC:MSA n = 3). Detection of sentinel lymph
      nodes was attempted after injecting ICG:MSA in the mouse tongue cancer model (n =
      3). During the operation, lymph nodes were easily identified and resected using
      ICFIS without the aid of other magnifiers. In the rabbit tongue cancer model (n =
      3), the ICFIS equipped with 30-degree endoscopy was used to confirm the
      feasibility of endoscopic sentinel lymph node biopsy. The entire sentinel lymph
      node biopsy procedure was performed using the ICFIS with the 30-degree endoscope.
      We detected and dissected sentinel lymph nodes in the rabbit model without the
      other sentinel lymph node detection tools. CONCLUSION: We confirmed the
      usefulness of sentinel lymph node biopsy using a near infrared fluorescence
      technique and endoscopic system. Avoidance of radiation exposure and shine
      through phenomena, which are problems of sentinel lymph node biopsy using
      conventional radioisotopes, are advantages of our surgical technique. By
      combining the endoscopic system with a sentinel lymph node biopsy procedure, we
      avoided visible neck scars, which lead to excellent cosmetic outcomes. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 128:E135-E140, 2018.

PMID- 29214647
TI  - Antagonistic pleiotropy and mutation accumulation contribute to age-related
      decline in stress response.
AB  - As organisms age, the effectiveness of natural selection weakens, leading to age
      related decline in fitness-related traits. The evolution of age-related changes
      associated with senescence is likely influenced by mutation accumulation (MA) and
      antagonistic pleiotropy (AP). MA predicts that age-related decline in fitness
      components is driven by age-specific sets of alleles, nonnegative genetic
      correlations within trait across age, and an increase in the coefficient of
      genetic variance. AP predicts that age-related decline in a trait is driven by
      alleles with positive effects on fitness in young individuals and negative
      effects in old individuals, and is expected to lead to negative genetic
      correlations within traits across age. We build on these predictions using an
      association mapping approach to investigate the change in additive effects of
      SNPs across age and among traits for multiple stress-response fitness-related
      traits, including cold stress with and without acclimation and starvation
      resistance. We found support for both MA and AP theories of aging in the age
      related decline in stress tolerance. Our study demonstrates that the evolution of
      age-related decline in stress tolerance is driven by a combination of alleles
      that have age-specific additive effects, consistent with MA, as well as
      nonindependent and antagonistic genetic architectures characteristic of AP.

PMID- 29214648
TI  - Nonlinear disposition of lithium in rats and saturation of its tubular
      reabsorption by the sodium-phosphate cotransporter as a cause.
AB  - We previously reported the contribution of sodium-phosphate cotransporter to the
      tubular reabsorption of lithium in rats. In the present study, the dose
      dependency of the renal handling of lithium was examined in rats. When lithium
      chloride at 1.25 mg/kg, 2.5 mg/kg and 25 mg/kg was intravenously injected as a
      bolus, the areas under the plasma concentration-time curve of lithium until 60
      minutes were calculated to be 6.23 mEq.min/l, 8.77 mEq.min/l and 64.6 mEq.min/l,
      respectively. The renal clearance of lithium and its fractional excretion
      increased with increments in the dose administered. The renal clearance of
      lithium strongly correlated with the urinary excretion rate of phosphate in the
      1.25 mg/kg group (r = 0.840) and 2.5 mg/kg group (r = 0.773), whereas this
      correlation was weak in the 25 mg/kg group (r = 0.306). The infusion of
      foscarnet, a typical inhibitor of sodium-phosphate cotransporter, decreased the
      fractional reabsorption of lithium in rats administered lithium chloride at 2.5
      mg/kg, but did not affect it in rats administered 25 mg/kg. These results
      demonstrate the nonlinearity of the renal excretion of lithium in rats, with the
      saturation of lithium reabsorption by the sodium-phosphate cotransporter
      potentially being involved.

PMID- 29214649
TI  - Climate-driven build-up of temporal isolation within a recently formed avian
      hybrid zone.
AB  - Divergence in the onset of reproduction can act as an important source of
      reproductive isolation (i.e., allochronic isolation) between co-occurring young
      species, but evidence for the evolutionary processes leading to such divergence
      is often indirect. While advancing spring seasons strongly affect the onset of
      reproduction in many taxa, it remains largely unexplored whether contemporary
      spring advancement directly affects allochronic isolation between young species.
      We examined how increasing spring temperatures affected onset of reproduction and
      thereby hybridization between pied and collared flycatchers (Ficedula spp.)
      across habitat types in a young secondary contact zone. We found that both
      species have advanced their timing of breeding in 14 years. However, selection on
      pied flycatchers to breed earlier was weaker, resulting in a slower response to
      advancing springs compared to collared flycatchers and thereby build-up of
      allochronic isolation between the species. We argue that a preadaptation to a
      broader niche use (diet) of pied flycatchers explains the slower response to
      raising spring temperature, but that reduced risk to hybridize may contribute to
      further divergence in the onset of breeding in the future. Our results show that
      minor differences in the response to environmental change of co-occurring closely
      related species can quickly cause allochronic isolation.

PMID- 29214650
TI  - Perampanel, an AMPA receptor antagonist: From clinical research to practice in
      clinical settings.
AB  - Epileptic seizures are refractory to treatment in approximately one-third of
      patients despite the recent introduction of many newer antiepileptic drugs
      (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel
      is a first-in-class non-competitive selective AMPA receptor antagonist with a
      unique mechanism of action. Clinical efficacy and safety of perampanel as
      adjunctive treatment for focal seizures with/without secondary generalization (+/
      SG) and primary generalized tonic-clonic (PGTC) seizures have been established in
      five phase 3 randomized controlled trials (RCTs), and a long-term extension
      study, and perampanel is approved as monotherapy for focal seizures +/-SG in the
      USA. In patients with focal seizures +/-SG, add-on perampanel resulted in median
      percent reduction in seizure frequency 23.3%-34.5% and >=50% responder rate 28.5%
      37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively.
      Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; >=50%
      responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency
      12.5%-16.9%; >=50% responder rate 22.2%-42.9%) is similar to those in adults, and
      results remain comparable between Asian (reduction in seizure frequency 17.3%
      38.0%) and global populations. Perampanel has been extensively studied in real
      world clinical practice, with similar efficacy and safety results to the RCTs
      (>=50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation,
      dizziness, ataxia, and behavioral changes). Real-world observational studies
      suggest that perampanel tolerability can be improved by slow titration (2 mg
      every 2-4 weeks), and bedtime administration can mitigate somnolence and
      dizziness. Counseling about the potential for behavioral changes and close
      monitoring are recommended.

PMID- 29214651
TI  - Electroencephalography and behavior patterns during experimental status
      epilepticus.
AB  - OBJECTIVE: To characterize the evolution of behavioral and electrographic
      seizures in an experimental electrical stimulation-based model of status
      epilepticus (SE) in C57Bl/6 mice, and to relate SE to various outcomes, including
      death and epileptogenesis. METHODS: SE was induced by continuous hippocampal
      stimulation and was evaluated by review of electroencephalographic recordings,
      spectral display, and behavior. RESULTS: Seizures were initially locked to the
      electrical trains but later became independent of them. Following the end of
      stimulation, autonomous seizures continued for >5 minutes in 85% of the animals.
      There was ongoing 2-3-Hz rhythmic, high-amplitude, slow spike-wave discharges
      (HASDs) associated with purposeless, repetitive, continuously circling and
      exploratory behavior. There were high-amplitude fast discharges (HAFDs)
      associated with worsening of behavioral seizures that were interspersed with the
      ongoing HASDs. Death during SE occurred in 23% of the animals, and it was
      preceded by a stage 5 behavioral seizure. In the waning stage of SE, severe
      seizures and HAFDs dissipated, HASDs slowed down, and normal behavior was
      restored in most animals. Epilepsy developed in 33% of the animals monitored
      after SE. SIGNIFICANCE: The electrical stimulation model of SE can be used to
      study mechanisms of SE and its adverse consequences, including death and
      epileptogenesis.

PMID- 29214653
TI  - Administrative billing codes accurately identified occurrence of electrical
      cardioversion and ablation/maze procedures in a prospective cohort study of
      atrial fibrillation patients.
AB  - BACKGROUND: Administrative billing codes for electrical cardioversion and
      ablation/maze procedures may be useful for atrial fibrillation (AF) research if
      the codes are accurate relative to medical record documentation. HYPOTHESIS:
      Administrative billing codes accurately identify occurrence of electrical
      cardioversion and ablation/maze procedures in AF patients. METHODS: We studied
      adults ages 30 to 84 who experienced new-onset AF between October 2001 and
      December 2004 in Group Health Cooperative (acquired by Kaiser Permanente in
      2017), an integrated healthcare system in Washington state and northern Idaho.
      Using medical record review as the gold standard, we calculated sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      for 3 administrative billing codes for electrical cardioversion and 3 codes for
      AF ablation/maze procedures. RESULTS: Of 1953 study participants, during a mean
      (SD) of 1.5 (0.7) years of follow-up after AF onset, 470 (24%) experienced
      electrical cardioversion and 44 (2%) experienced ablation/maze procedures,
      according to medical record review. For electrical cardioversion, individual
      codes had 7.7% to 76.4% sensitivity, >99% specificity, 83.7% to 96.5% PPV, and
      77.3% to 93.0% NPV. Considering any of 3 codes (code 1 or code 2 or code 3)
      improved sensitivity to 84.9%. For ablation/maze, individual codes had 18.2% to
      47.7% sensitivity, >99% specificity, 66.7% to 95.5% PPV, and >98% NPV.
      Considering any of 3 codes improved sensitivity to 84.1%. CONCLUSIONS:
      Administrative billing data accurately identified electrical cardioversion and
      ablation/maze procedures and can be used instead of medical record review. Our
      findings apply to healthcare settings with available administrative billing
      databases.

PMID- 29214652
TI  - Pharmacology in translation: the preclinical and early clinical profile of the
      novel alpha2/3 functionally selective GABAA receptor positive allosteric
      modulator PF-06372865.
AB  - BACKGROUND AND PURPOSE: Benzodiazepines, non-selective positive allosteric
      modulators (PAMs) of GABAA receptors, have significant side effects that limit
      their clinical utility. As many of these side effects are mediated by the alpha1
      subunit, there has been a concerted effort to develop alpha2/3 subtype-selective
      PAMs. EXPERIMENTAL APPROACH: In vitro screening assays were used to identify
      molecules with functional selectivity for receptors containing alpha2/3 subunits
      over those containing alpha1 subunits. In vivo receptor occupancy (RO) was
      conducted, prior to confirmation of in vivo alpha2/3 and alpha1 pharmacology
      through quantitative EEG (qEEG) beta frequency and zolpidem drug discrimination
      in rats respectively. PF-06372865 was then progressed to Phase 1 clinical trials.
      KEY RESULTS: PF-06372865 exhibited functional selectivity for those receptors
      containing alpha2/3/5 subunits, with significant positive allosteric modulation
      (90-140%) but negligible activity (<=20%) at GABAA receptors containing alpha1
      subunits. PF-06372865 exhibited concentration-dependent occupancy of GABAA
      receptors in preclinical species. There was an occupancy-dependent increase in
      qEEG beta frequency and no generalization to a GABAA alpha1 cue in the drug
      discrimination assay, clearly demonstrating the lack of modulation at the GABAA
      receptors containing an alpha1 subtype. In a Phase 1 single ascending dose study
      in healthy volunteers, evaluation of the pharmacodynamics of PF-06372865
      demonstrated a robust increase in saccadic peak velocity (a marker of alpha2/3
      pharmacology), increases in beta frequency qEEG and a slight saturating increase
      in body sway. CONCLUSIONS AND IMPLICATIONS: PF-06372865 has a unique clinical
      pharmacology profile and a highly predictive translational data package from
      preclinical species to the clinical setting.

PMID- 29214654
TI  - Role of the innate immune system in the neuropathological consequences induced by
      adolescent binge drinking.
AB  - Adolescence is a critical stage of brain maturation in which important plastic
      and dynamic processes take place in different brain regions, leading to
      development of the adult brain. Ethanol drinking in adolescence disrupts brain
      plasticity and causes structural and functional changes in immature brain areas
      (prefrontal cortex, limbic system) that result in cognitive and behavioral
      deficits. These changes, along with secretion of sexual and stress-related
      hormones in adolescence, may impact self-control, decision making, and risk
      taking behaviors that contribute to anxiety and initiation of alcohol
      consumption. New data support the participation of the neuroimmune system in the
      effects of ethanol on the developing and adult brain. This article reviews the
      potential pathological bases that underlie the effects of alcohol on the
      adolescent brain, such as the contribution of genetic background, the
      perturbation of epigenetic programming, and the influence of the neuroimmune
      response. Special emphasis is given to the actions of ethanol in the innate
      immune receptor toll-like receptor 4 (TLR4), since recent studies have
      demonstrated that by activating the inflammatory TLR4/NFkappaB signaling response
      in glial cells, binge drinking of ethanol triggers the release of
      cytokines/chemokines and free radicals, which exacerbate the immune response that
      causes neuroinflammation/neural damage as well as short- and long-term
      neurophysiological, cognitive, and behavioral dysfunction. Finally, potential
      treatments that target the neuroimmune response to treat the neuropathological
      and behavioral consequences of adolescent alcohol abuse are discussed.

PMID- 29214655
TI  - An anatomic description of intrinsic brachial muscles in the crab-eating fox
      (Cerdocyon thous, Linnaeus 1776) and report of a variant arterial distribution.
AB  - The crab-eating fox (Cerdocyon thous) is a wild canid distributed throughout
      South America. It is one of the wild canids reported being hit by vehicles and
      injured in snares, thus inducing trauma or injury to the musculoskeletal system,
      possibly occurring in the brachial region. The main objective of this research
      was to provide an anatomic description of the crab-eating fox's intrinsic
      brachial muscles including shape, origin, insertion, innervation and arterial
      blood supply, compared with that of the domestic dog. We dissected from
      superficial to deep two thoracic limbs of seven dead specimens donated to the
      University of Caldas by CORPOCALDAS. These muscles presented anatomic
      characteristics similar to those reported in the domestic dog (Canis lupus
      familiaris) but with a variant in arterial blood supply, allowing us to suggest
      that surgical procedures that need the knowledge of intrinsic brachial muscles in
      the crab-eating fox may be homologous to the domestic dog. However, one should
      consider its variant arterial distribution by part of the collateral radial
      artery and deep brachial artery to prevent incorrect incisions that may damage
      these arteries.

PMID- 29214657
TI  - Varicella pseudo-Koebner phenomenon associated with vascular access opening.

PMID- 29214656
TI  - Screening active components of modified Xiaoyao powder as NRF2 agonists.
AB  - Nuclear factor (erythroid-derived 2)-like 2 (NRF2) regulates antioxidant enzymes
      and phase II detoxifying enzymes, such as NAD(P)H: quinone oxidoreductase 1
      (NQO1). Modified Xiaoyao powder (MXP) is most frequently used in the prevention
      and treatment of breast cancer in China. This study aimed to screen active
      components of MXP for antioxidant stress and chemoprevention, which depend on
      NRF2-NQO1 signalling pathway. A total of 25 monomeric compounds contained in MXP
      were screened using an antioxidant response element-luciferase reporter. The most
      potent antioxidant response element-luciferase inducers were chosen to further
      examine their effects on NRF2 and NQO1 in MCF-7 cells. These results were then
      confirmed by determining the oxidative stress levels and chemopreventive effect
      on inhibiting carcinogenesis transformation in NRF2 knockdown (NRF2KD ) and NRF2
      wild-type MCF-10A cells. We found that quercetin, kaempferol, and atractylenolide
      II in MXP were potent NRF2 inducers, which could up-regulate the expression of
      NRF2 and its downstream enzymes NQO1. In addition, these components could
      decrease reduced oxidative stress and inhibit carcinogenesis transformation,
      which depended on NRF2-NQO1 pathway. In conclusion, NRF2-NQO1 pathway plays an
      essential role in mediating the activity of MXP and its active components, at
      least in part; some beneficial effects of MXP may be applicable to breast cancer
      chemoprevention. Our study firstly found MXP active components including
      quercetin, kaempferol, and atractylenolide II. Our results firstly demonstrate
      that NRF2-NQO1 pathway plays an essential role in mediating the activity of MXP
      and its active components in breast cancer chemoprevention. Our study firstly
      found that atractylenolide II is a novel NRF2 inducer.

PMID- 29214658
TI  - Identifying environmental barriers to participation: Usability of a health
      literacy informed problem-identification approach for parents of young children
      with developmental disabilities.
AB  - BACKGROUND: Parents of very young children recently diagnosed with developmental
      disabilities (DD) need to identify environmental barriers to their children's
      participation and adopt an adaptive orientation to solving these problems. Given
      the health service disparities for diverse families, parents may benefit from
      easy to use problem-identification approaches that address environmental barriers
      stemming from community and policy contexts. This feasibility study evaluated the
      usability of a health literacy-informed, structured, environment-focused problem
      identification approach for parents of young children with DD. METHODS: We used
      purposeful, convenience sampling to enrol 9 mothers of children ages 1-3 with DD
      (4 racial/ethnic minorities, 3 high school education, 4 annual household income
      <$20,000). We developed a structured problem-identification approach guided by a
      social ecological model featuring home, community, and policy contexts. The
      approach was applied to 3 short stories during a narrative elicitation interview.
      Two researchers independently coded parent responses for the type of barrier and
      solution identified with and without the approach. RESULTS: Parents identified
      121 environmental barriers without the approach. When using the approach and
      prompted to consider home, community, and policy barriers, parents identified an
      additional 222 environmental barriers; the greatest number of barriers were
      aligned with International Classification of Functioning, Disability, and Health
      Children and Youth environment Chapter 5 "Services, systems, and policies." Using
      the approach, parents with a postgraduate education and annual household income
      >$80,000 identified the most environmental barriers, and parents reporting the
      lowest annual household incomes identified the fewest environmental barriers.
      When parents attributed participation challenges to an environmental barrier,
      ~57% of solutions required parents to interact with individuals at the community
      or policy level. CONCLUSIONS: This study suggests that parents with a range of
      background characteristics can use a structured, environment-focused problem
      identification approach. With the approach, parents are more likely to attribute
      participation challenges to environmental barriers and adopt a problem-solving
      orientation focused on changes to the community and policy context.

PMID- 29214659
TI  - 2D speckle tracking echocardiography of the right ventricle free wall in SCUBA
      divers after single open sea dive.
AB  - The presence of circulating gas bubbles and their influence on pulmonary and
      right heart hemodynamics was reported after uncomplicated self-contained
      underwater breathing apparatus (SCUBA) dive(s). Improvements in cardiac imaging
      have recently focused great attention on the right ventricle (RV). The aim of our
      study was to evaluate possible effects of a single air SCUBA dive on RV function
      using 2D speckle tracking echocardiography in healthy divers after single open
      sea dive to 18 meters of seawater, followed by bottom stay of 47 minutes with a
      direct ascent to the surface. Twelve experienced male divers (age 39.5 +/- 10.5
      years) participated in the study. Echocardiographic assessment of the right
      ventricular function (free wall 2 D strain, tricuspid annular planes systolic
      excursion [TAPSE], lateral tricuspid annular peak systolic velocity [RV s'] and
      fractional area change [FAC]) was performed directly prior to and 30, 60, 90 and
      120 minutes after surfacing. Two-dimensional strain of all three segments of free
      right ventricular wall showed a significant increase in longitudinal shortening
      in post-dive period for maximally 26% (basal), 15.4% (mid) and 16.3% (apical) as
      well as TAPSE (11.6%), RV FAC (19.2%), RV S' (12.7%) suggesting a rise in
      systolic function of right heart. Mean pulmonary arterial pressure (mean PAP)
      increased post-dive from 13.3 mmHg to maximally 23.5 mmHg (P = .002), indicating
      increased RV afterload. Our results demonstrated that single dive with
      significant bubble load lead to increase in systolic function and longitudinal
      strain of the right heart in parallel with increase in mean PAP.

PMID- 29214660
TI  - Thulium laser-assisted endoscopic third ventriculostomy: Determining safe laser
      settings using in vitro model and 2 year follow-up results in 106 patients.
AB  - BACKGROUND AND OBJECTIVE: Endoscopic third ventriculostomy is used to treat
      hydrocephalus. Different laser wavelengths have been proposed for laser-assisted
      endoscopic third ventriculostomies over the last decades. The aim of this study
      was to evaluate Thulium laser endoscopic third ventriculostomy heat penetration
      in the surrounding environment of the floor of the third ventricle in an in vitro
      setting with visualization of thermal distribution. Subsequently 106 Thulium
      laser endoscopic third ventriculostomy procedures were retrospectively analyzed
      to demonstrate safety. METHODS: The in vitro visualization was based on the color
      Schlieren method. The heat penetration was measured beneath a tissue phantom of
      the floor of the third ventricle with a fiber of 365 MUm in diameter at different
      energy settings; 1.0W (956 J/cm2 ), 2.0W (1,912 J/cm2 ), 4.0W (3,824 J/cm2 ), and
      7.0W (6,692 J/cm2 ), with a pulse duration of 1.0 second. All experiments were
      repeated five times. In addition, 106 Thulium laser endoscopic third
      ventriculostomy procedures between 2005 and 2015 were retrospectively analysed
      for etiology, sex, complications, and laser parameters. RESULTS: In the energy
      settings from 1.0 to 4.0 W, heat penetration depth beneath the phantom of the
      third ventricle did not exceed 1.5 mm. The heat penetration depth at 7 W,
      exceeded 6 mm. The clinical overall success rate was 80% at the 2-year follow-up
      study. Complications occurred in 5% of the procedures. In none of the 106
      investigated clinical patients bleeding or damage to the basilar artery was
      encountered due to Thulium laser ablation. CONCLUSIONS: The in vitro experiments
      show that under 4.0W the situation is considered safe, due to low penetration of
      heat, thus the chance of accidentally damaging critical structures like the
      basilar artery is very small. The clinical results show that the Thulium laser
      did not cause any bleeding of the basilar artery, and is a safe technique for
      laser endoscopic third ventriculostomy. Lasers Surg. Med. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29214661
TI  - Reverse mapping method for complex polymer systems.
AB  - We present a comprehensive approach for reverse mapping of complex polymer
      systems in which the connectivity is created by the simulation of chemical
      reactions at the coarse-grained scale. Within the work, we use a recently
      developed generic adaptive reverse mapping procedure that we adapt to handle the
      varying connectivity structure resulting from the chemical reactions. The method
      is independent of the coarse-grained and fine-grained force-fields by design and
      relies only on a single control parameter. We employ the approach to reverse map
      four different systems: a three-component epoxy network, a trimethylol melamine
      network, a hyperbranched polymer, and a polyethylene terephthalate. In the case
      of the epoxy network, we use two fine-scale representations: fully atomistic and
      united-atom. Whereas the trimethylol melamine network the hyperbranched polymer
      and the polyethylene terephthalate are reverse mapped to the fully atomistic
      description. After the reverse mapping, we examine the fine-grained structure by
      comparing the radial distribution functions with respect to the control
      parameter. Moreover, in the case of the epoxy we perform tensile-test experiments
      and examine the resulting Young's modulus. In all cases, we show how the
      properties of the reverse mapped systems depend on the control parameters. In
      general, we see that the results are relatively insensitive to the control
      parameter and the resulting atomistic systems are stable. Only for the
      trimethylol melamine network, we notice chemically incorrect conformations when
      the reverse mapping is performed too fast. We provide a remedy for this issue.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29214662
TI  - Airborne particulate concentration during laser hair removal: A comparison
      between cold sapphire with aqueous gel and cryogen skin cooling.
AB  - BACKGROUND: High concentrations of sub-micron nanoparticles have been shown to be
      released during laser hair removal (LHR) procedures. These emissions pose a
      potential biohazard to healthcare workers that have prolonged exposure to LHR
      plume. OBJECTIVE: We sought to demonstrate that cold sapphire skin cooling done
      in contact mode might suppress plume dispersion during LHR. METHODS: A total of
      11 patients were recruited for laser hair removal. They were treated on the legs
      and axilla with a 755 or 1064 nm millisecond-domain laser equipped with either
      (i) cryogen spray (CSC); (ii) refrigerated air (RA); or (iii) contact cooling
      with sapphire (CC). Concentration of ultrafine nanoparticles <1 MUm were measured
      just before and during LHR with the three respective cooling methods. RESULTS:
      For contact cooling (CC), counts remained at baseline levels, below 3,500 parts
      per cubic centimeter (ppc) for all treatments. In contrast, the CSC system
      produced large levels of plume, peaking at times to over 400,000 ppc. The CA
      cooled system produced intermediate levels of plume, about 35,000 ppc (or about
      10* baseline). CONCLUSIONS: Cold Sapphire Skin cooling with gel suppresses plume
      during laser hair removal, potentially eliminating the need for smoke evacuators,
      custom ventilation systems, and respirators during LHR. Lasers Surg. Med. 50:280
      283, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29214663
TI  - Impact of Preoperative Ultrasonographic Evaluation for Detection of a Viable
      Testis in Patients With a Unilateral Nonpalpable Testis.
AB  - OBJECTIVES: To investigate the impact of preoperative ultrasonography (US) for
      detecting a viable testis in patients with a unilateral nonpalpable testis.
      METHODS: Patients with a unilateral nonpalpable testis or unilateral palpable
      undescended testis who underwent preoperative US were enrolled. Patients were
      divided into 3 groups as follows: nonpalpable testis/no testis (n = 27), which
      included patients who had a unilateral nonpalpable testis with no viable testis
      detected at surgery; nonpalpable testis/viable testis (n = 10), which included
      patients who had a unilateral nonpalpable testis with a viable testis identified
      at surgery; and palpable undescended testis (n = 63), which included patients who
      had a unilateral palpable undescended testis. Preoperative US findings were
      compared among each group. RESULTS: The testicular volume on the contralateral
      descended side in the nonpalpable testis/no testis group was significantly
      greater than that in the nonpalpable testis/viable testis and palpable
      undescended testis groups. When a testicular volume of 0.54 mL was used as the
      cutoff value, the sensitivity, specificity, positive predictive value, and
      negative predictive value for the presence of the affected testis were 75.3%,
      100%, 100%, and 60.0%, respectively. The testis on the affected side was detected
      in none of the nonpalpable testis/no testis group, 7 of the nonpalpable
      testis/viable testis group, and all of the palpable undescended testis group.
      When a visible testis on the affected side and a testicular volume of 0.54 mL or
      less were defined as positive, all patients in the nonpalpable testis/viable
      testis and palpable undescended testis groups had positive findings versus none
      in the nonpalpable testis/no testis group. CONCLUSIONS: Preoperative US provides
      valuable information for predicting the presence of a viable testis in patients
      with a unilateral nonpalpable testis by estimating both the unaffected testis and
      the affected side.

PMID- 29214664
TI  - Lipoid proteinosis: towards predictive clinical clues.

PMID- 29214665
TI  - Cephalic muscle development in the Australian lungfish, Neoceratodus forsteri.
AB  - Lungfishes are the extant sister group of tetrapods. As such, they are important
      for the study of evolutionary processes involved in the water to land transition
      of vertebrates. The evolution of a true neck, that is, the complete separation of
      the pectoral girdle from the cranium, is one of the most intriguing morphological
      transitions known among vertebrates. Other salient changes involve new
      adaptations for terrestrial feeding, which involves both the cranium and its
      associated musculature. Historically, the cranium has been extensively
      investigated, but the development of the cranial muscles much less so. Here, we
      present a detailed study of cephalic muscle development in the Australian
      lungfish, Neoceratodus forsteri, which is considered to be the sister taxon to
      all other extant lungfishes. Neoceratodus shows several developmental patterns
      previously described in other taxa; the tendency of muscles to develop from
      anterior to posterior, from their region of origin toward insertion, and from
      lateral to ventral/medial (outside-in), at least in the branchial arches. The
      m.protractor pectoralis appears to develop as an extension of the most posterior
      m.levatores arcuum branchialium, supporting the hypothesis that the m.cucullaris
      and its derivatives (protractor pectoralis, levatores arcuum branchialium) are
      branchial muscles. We present a new hypothesis regarding the homology of the
      ventral branchial arch muscles (subarcualis recti and obliqui, transversi
      ventrales) in lungfishes and amphibians. Moreover, the morphology and development
      of the cephalic muscles confirms that extant lungfishes are neotenic and have
      been strongly influenced via paedomorphosis during their evolutionary history.

PMID- 29214666
TI  - Low-level ultrahigh-frequency and ultrashort-pulse blue laser irradiation
      enhances osteoblast extracellular calcification by upregulating proliferation and
      differentiation via transient receptor potential vanilloid 1.
AB  - BACKGROUND AND OBJECTIVE: Low-level laser irradiation (LLLI) exerts various
      biostimulative effects, including promotion of wound healing and bone formation;
      however, few studies have examined biostimulation using blue lasers. The purpose
      of this study was to investigate the effects of low-level ultrahigh-frequency
      (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts. STUDY
      DESIGN/ MATERIALS AND METHODS: The MC3T3-E1 osteoblast cell line was used in this
      study. Following LLLI with a 405 nm newly developed UHF-USP blue laser (80 MHz,
      100 fs), osteoblast proliferation, and alkaline phosphatase (ALP) activity were
      assessed. In addition, mRNA levels of the osteoblast differentiation markers,
      runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase
      (Alp), and osteopontin (Opn) was evaluated, and extracellular calcification was
      quantified. To clarify the involvement of transient receptor potential (TRP)
      channels in LLLI-induced biostimulation, cells were treated prior to LLLI with
      capsazepine (CPZ), a selective inhibitor of TRP vanilloid 1 (TRPV1), and
      subsequent proliferation and ALP activity were measured. RESULTS: LLLI with the
      405 nm UHF-USP blue laser significantly enhanced cell proliferation and ALP
      activity, compared with the non-irradiated control and LLLI using continuous-wave
      mode, without significant temperature elevation. LLLI promoted osteoblast
      proliferation in a dose-dependent manner up to 9.4 J/cm2 and significantly
      accelerated cell proliferation in in vitro wound healing assay. ALP activity was
      significantly enhanced at doses up to 5.6 J/cm2 , and expression of Osx and Alp
      mRNAs was significantly increased compared to that of the control on days 3 and 7
      following LLLI at 5.6 J/cm2 . The extent of extracellular calcification was also
      significantly higher as a result of LLLI 3 weeks after the treatment. Measurement
      of TRPV1 protein expression on 0, 3, and 7 days post-irradiation revealed no
      differences between the LLLI and control groups; however, promotion of cell
      proliferation and ALP activity by LLLI was significantly inhibited by CPZ.
      CONCLUSION: LLLI with a 405 nm UHF-USP blue laser enhances extracellular
      calcification of osteoblasts by upregulating proliferation and differentiation
      via TRPV1. Lasers Surg. Med. 50:340-352, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29214667
TI  - Effect of ribonucleotide reductase M1 expression on overall survival in patients
      with pancreatic cancer receiving gemcitabine chemotherapy: A literature-based
      meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: The prognostic value of ribonucleotide reductase M1
      (RRM1) in patients with pancreatic cancer receiving gemcitabine chemotherapy has
      been evaluated in several studies. However, the conclusions remain controversial.
      METHODS: By searching the PubMed and Embase databases, we conducted a meta
      analysis to evaluate the prognostic significance of RRM1 expression in patients
      with pancreatic cancer receiving gemcitabine chemotherapy. Studies were pooled,
      and the hazard ratio (HR) and its corresponding 95% confidence interval (CI) were
      calculated. RESULTS: Nine relevant articles were included for this meta-analysis
      study. Our results revealed that the high-RRM1 expression patients had
      significantly poorer overall survival (HR = 1.70, 95% CI = 1.33-2.16,
      Pheterogeneity  = .061, I2  = 44.8%) and disease-free survival (HR = 1.84, 95% CI
      = 1.56-2.18, Pheterogeneity  = .669, I2  = 0%) than the low-RRM1 expression
      patients. Furthermore, a statistically significant association between RRM1
      expression and OS was found among both Japanese (HR = 1.80, 95% CI = 1.36-2.37,
      Pheterogeneity  = .843, I2  = 0%) and American patients (HR = 1.76, 95% CI = 1.60
      1.94, Pheterogeneity  = .439, I2  = 0%). WHAT IS NEW AND CONCLUSION: In
      conclusion, the expression of RRM1 can be considered a predictor of poor survival
      in patients with pancreatic cancer receiving gemcitabine chemotherapy. RRM1
      expression assessment could provide more detailed information for patients with
      pancreatic cancer and could be used to optimize therapeutic schemes.

PMID- 29214668
TI  - Photofrin(r) photodynamic therapy with intratumor photosensitizer injection
      provides similar tumor response while reducing systemic skin photosensitivity:
      Pilot murine study.
AB  - OBJECTIVES: The goal of this study was to compare tumor response to Photofrin(r)
      photodynamic therapy using intravenous and intratumoral injection of
      photosensitizer. Systemic skin photosensitivity and photosensitizer distribution
      were also compared between the two delivery methods. METHODS: SCCVII tumors were
      initiated in the hind legs of female C3H mice and grown to a volume of ~1,000 mm3
      . Photofrin(r) was delivered intravenously via the tail vein at a concentration
      of 2 mg/kg or intratumorally at concentrations ranging from 0.5-2 mg/kg. A 630 nm
      laser illumination was delivered via interstitial diffuser placement at a fluence
      rate of 400 mW/cm and fluence of 100 J/cm. Mice were maintained under normal room
      lighting for 24 hours after treatment, at which point photographs were captured
      for assessment of skin photosensitivity. Animals were then sacrificed, and their
      tumors were excised, sectioned, imaged, and stained with hematoxylin and eosin
      (H&E). H&E slides were imaged to assess necrosis post-PDT, and skin photographs
      were evaluated by two blinded reviewers for quantification of skin
      photosensitivity. Whole-body fluorescence imaging was performed before and after
      photodynamic therapy. RESULTS: Tumor necrosis was not significantly different
      based on treatment group (P = 0.33), while skin photosensitivity was
      significantly reduced in animals that received Photofrin(r) intratumorally (P =
      0.0005). Fluorescence imaging revealed similar photosensitizer fluorescence in
      excised tumors for intratumor and intravenous injection of Photofrin(r) (P =
      0.48), although fluorescence decreased significantly with decreasing intratumor
      injection concentration (P= 0.01). CONCLUSIONS: This pilot study shows that
      intratumoral administration of Photofrin(r) has the potential to produce similar
      tumor outcomes, while reducing systemic skin photosensitivity. Further studies
      are warranted to characterize and optimize intratumor delivery. Lasers Surg.
      50:476-482, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29214669
TI  - Tooth loss and its relationship with protein intake by elderly Brazilians-A
      structural equation modelling approach.
AB  - OBJECTIVE: This study aimed at assessing the relationship between self-perceived
      tooth loss and wearing dentures, on the one hand, and the consumption of protein,
      on the other hand, among the elderly population of Botucatu, SP. Food consumption
      tends to decrease with ageing, especially protein intake, and one of the causes
      could be the precariousness of oral health. Several risk factors associated with
      deficient dietary protein intake have been identified, namely greater physical
      dependence, reduced caloric intake and food insecurity, but no studies have
      analysed whether tooth loss and prostheses interfere with protein intake.
      METHODS: An interview was conducted among 365 elderly individuals, in which we
      examined oral health-related quality of life (OHRQoL) as the only latent
      variable, in a 24-hour nutritional assessment dietary recall repeated 3 times,
      conducted in person by a trained nutritionist and also performed an analysis of
      nutritional needs using the Nutrition Data System Research (NDSR) Program.
      RESULTS: The structural equation model, performed using Stata v.14, showed that
      lack of teeth (standardised coefficient [SC] = 0.21, P < .001), and prosthesis
      use (SC = -0.21, P < .001) was associated with OHRQoL. Lack of teeth had a direct
      effect on the consumption of animal protein (SC = 0.08, P = .02), a strong total
      effect on animal protein intake (SC = 0.51, P = .04) and a medium effect on total
      protein intake (SC = 0.20, P = .03), adjusted for confounders (depression and
      medical problems). CONCLUSION: Tooth loss had a strong and significant total
      effect on animal protein intake and a medium effect on total protein intake among
      elderly Brazilians.

PMID- 29214670
TI  - Recanalization of native superficial femoral artery chronic total occlusion after
      failed femoropopliteal bypass in patients with critical limb ischemia.
AB  - OBJECTIVES: This study aimed to examine the outcomes of endovascular
      recanalization for native superficial femoral artery (SFA) chronic total
      occlusion (CTO) in patients with critical limb ischemia (CLI) after
      femoropopliteal bypass failure with limited surgical revascularization options.
      BACKGROUND: Endovascular recanalization of native artery occlusions has been
      recently used as a new alternative for threatened limbs after bypass graft
      occlusion. The feasibility and efficacy has not been widely reported. METHODS: We
      retrospectively analyzed 45 consecutive patients (45 limbs) undergoing
      endovascular recanalization of native SFA occlusion following failed
      femoropopliteal bypass between June 2010 and December 2016. RESULTS: All limbs
      had Transatlantic Inter-Society Consensus class C (26.7%, 12/45) or D (73.3%,
      33/45) lesions with a mean lesion length of 29.8 cm. The technical success rate
      was 95.6% (43/45 limbs). The ABI showed a significant increase from 0.3 +/- 0.1
      pre-procedure to 0.7 +/- 0.1 post-procedure (P < 0.01). Two early (<30 days)
      below-knee amputations due to acute thrombotic ischemia occurred during
      perioperative period and resulted in one death due to myocardial infarction. The
      mean follow-up was 42.7 months (1-62 months). Two patients were lost to follow
      up. The primary patency rates at 12 and 36 months were 54% and 51%, respectively.
      Secondary patency rates at 12 and 36 months were 78% and 61%, respectively. Limb
      salvage rate was 95% and amputation-free survival rate was 88% at both 12 and 36
      months. CONCLUSION: Recanalization of native SFA CTO due to failed
      femoropopliteal bypass offers a feasible and safe alternative to surgical
      reconstruction with acceptable limb salvage.

PMID- 29214671
TI  - Multilayer Cucurbit[6]uril-Based Magnetic Nanoparticles Prepared by Host-Guest
      Interaction: Remarkable Adsorbent for Low Density Lipoprotein Removal from
      Plasma.
AB  - Efficient removal of low density lipoprotein (LDL) is a key challenge due to its
      high level in plasma as a primary risk factor in the pathogenesis of
      atherosclerotic cardiovascular disease. In this work, a facile synthesis strategy
      based on host-guest interactions was developed to prepare multilayer
      cucurbit[6]uril-based magnetic nanoparticles, MNPs-(HA-DAH5 /HA-CB[6]5 ). The
      compound was employed as a blood purification material for the removal of LDL
      from plasma because it had good blood compatibility and could be easily separated
      with an external magnet. The efficient removal of LDL was attributed to the
      electrostatic interactions between the positive charged apoB-100 domain of LDL
      and the negative charged adsorbent. Moreover, the prepared material exhibited
      high recyclability and could release LDL in physiological saline for recyclable
      use. MNPs-(HA-DAH5 /HA-CB[6]5 ) offered promising perspectives and broad
      applications in extracorporeal treatment for the removal of LDL.

PMID- 29214672
TI  - Region-specific deletions of the glutamate transporter GLT1 differentially affect
      seizure activity and neurodegeneration in mice.
AB  - Glial glutamate transporter GLT1 plays a key role in the maintenance of
      extracellular glutamate homeostasis. Recent human genetic studies have suggested
      that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple
      seizure types. Consistent with these findings, global GLT1 null mice show lethal
      spontaneous seizures. The consequences of GLT1 dysfunction vary between different
      brain regions, suggesting that the role of GLT1 dysfunction in epilepsy may also
      vary with brain regions. In this study, we generated region-specific GLT1
      knockout mice by crossing floxed-GLT1 mice with mice that express the Cre
      recombinase in a particular domain of the ventricular zone. Selective deletion of
      GLT1 in the diencephalon, brainstem and spinal cord is sufficient to reproduce
      the phenotypes (excess mortality, decreased body weight, and lethal spontaneous
      seizure) of the global GLT1 null mice. By contrast, dorsal forebrain-specific
      GLT1 knockout mice showed nonlethal complex seizures including myoclonic jerks,
      hyperkinetic running, spasm and clonic convulsion via the activation of NMDA
      receptors during a limited period from P12 to P14 and selective neuronal death in
      cortical layer II/III and the hippocampus. Thus, GLT1 dysfunction in the dorsal
      forebrain is involved in the pathogenesis of infantile epilepsy and GLT1 in the
      diencephalon, brainstem and spinal cord may play a critical role in preventing
      seizure-induced sudden death.

PMID- 29214673
TI  - Assessing truncal obesity in predicting cardiometabolic risk in children:
      clinical measures versus dual-energy X-ray absorptiometry.
AB  - AIM: The objectives of this study were to 1) compare the accuracy of waist:hip
      ratio (WHR) and waist:height ratio (WHtR) by determining their association with
      reference-standard measures derived from dual-energy X-ray absorptiometry (DXA)
      and 2) assess the relationship of DXA, WHR and WHtR to measures of dyslipidemia,
      insulin resistance and inflammation in children. METHODS: Subjects aged four to
      21 were prospectively recruited. Truncal obesity by DXA was defined as the trunk
      fat:height ratio and trunk fat:nontrunk fat ratio. Three hundred and eight
      subjects were studied, and 246 (80%) were obese. RESULTS: There was a strong
      correlation between WHtR and trunk fat:height (r = 0.84, p < 0.01). DXA measures
      of truncal obesity had stronger correlations with measures of cardiometabolic
      risk than WHR and WHtR. Upon multivariable regression, only WHtR had independent
      associations with cholesterol/HDL, HOMA-IR and high-sensitivity c-reactive
      protein. CONCLUSION: WHtR is an accurate measure of truncal obesity. WHtR showed
      stronger associations with measures of insulin resistance and truncal obesity
      than WHR.

PMID- 29214675
TI  - Phenotyping the detrusor underactivity: Is it more important than categorizing
      the symptomatic presentation of detrusor underactivity?
AB  - AIMS: Recently, [Brown et al Neurourol Urodyn. 36:1151-1154, 2017] reported a
      remarkable study regarding detrusor underactivity (DU) by categorizing the
      possible phenotypes. Although this study presents novel findings on the possible
      phenotypes, several points need to be clarified further for a better
      understanding. METHODS: The methodology, especially regarding categorizing the
      phenotypes has been reviewed and comments have been added for better
      understanding of their study. RESULTS: To better understand novel results of
      their study, several points have to be considered, which include cluster analysis
      and categorization according to symptomatic presentations. CONCLUSIONS:
      Phenotyping by either etiologies or covariates and by syndromic presentations is
      not easy. Due to the aging features, multiple factors are needed during
      interpretation of the categorized phenotypes. Considering the advantage of the
      clinical benefit from the patient's viewpoint, categorization of syndromic
      symptomatic presentation using multiple validated tools including patient
      reported outcomes is needed.

PMID- 29214674
TI  - Neutrophil Extracellular Traps in Plasma from Dogs with Immune-mediated Hemolytic
      Anemia.
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) are part of the innate immune
      response and are essential in local pathogen control, but are associated with
      pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune
      mediated hemolytic anemia (IMHA) is a pro-inflammatory, prothrombotic disease
      associated with high mortality. HYPOTHESIS/OBJECTIVES: Neutrophil extracellular
      traps (NETs) are a feature of the inflammatory process in dogs with IMHA. The
      objective of the study was to evaluate plasma from dogs with IMHA for the
      presence of 2 indirect markers and 1 direct marker of NETs. ANIMALS: Healthy
      client-owned dogs (56) and hospitalized dogs with IMHA (n = 35). METHODS:
      Prospective study. Plasma samples for all dogs were evaluated for cell-free DNA
      using a fluorescence assay, histone-DNA (hisDNA) complex using an ELISA, and
      citrullinated histone H3 (specific for NETosis) using Western blot. Reference
      intervals were generated using plasma from healthy dogs. RESULTS: In dogs with
      IMHA, cell-free DNA concentration was above the reference interval in 17% of
      samples with a median (range) of 1.0 MUg/mL (0.1-17.3), and hisDNA concentration
      was above the reference interval in 94% of samples with a median (range) of 30.7
      * pooled normal plasma (PNP; 0.6-372.1). Western blot for citrullinated histone
      H3 identified detectable bands in 84% samples from dogs with IMHA. CONCLUSIONS
      AND CLINICAL IMPORTANCE: The assay for cell-free DNA detected evidence of NETs in
      fewer dogs than did the other approaches. Excessive NETs appears to be a feature
      of IMHA in dogs and contributions to the prothrombotic state deserve further
      study.

PMID- 29214676
TI  - Platelet function monitoring for stent thrombosis in critically III patients with
      an acute Coronary syndrome.
AB  - BACKGROUND: Patients after cardiac arrest or in cardiogenic shock due to acute
      coronary syndrome (ACS) are at high risk for stent thrombosis (ST) and recurrent
      cardiovascular events after primary percutaneous coronary intervention (PCI).
      High post-interventional platelet reactivity (HPR) might be an additional risk
      factor for ST in these critically ill patients. METHODS: Between 2006 and 2016,
      401 critically ill patients from a cardiologic intensive care unit underwent
      platelet function testing after primary PCI using whole blood impedance
      aggregometry. After exclusion of patients with an abnormal platelet count, 357
      patients have been included into the final analysis of this retrospective
      observational study. RESULTS: The incidence of definite early ST was 19.2% in
      patients with HPR to P2Y12 antagonists and 1.2% in patients without HPR.
      Likewise, the incidence of early ST in patients with HPR to acetylsalicylic acid
      (ASA) was 21.4% versus 1.8% in patients without HPR. In contrast, the incidence
      of late ST or recurrent myocardial infarction in untreated lesions was not
      associated with HPR to ASA or P2Y12 antagonists. CONCLUSIONS: Platelet function
      testing in critically ill ACS patients identified patients at high risk for early
      ST and might be beneficial for risk stratification.

PMID- 29214677
TI  - Highly Electrophilic, Catalytically Active and Redox-Responsive Cobaltoceniumyl
      and Ferrocenyl Triazolylidene Coinage Metal Complexes.
AB  - A convenient access to a triad of triazoles with ferrocenyl and cobaltoceniumyl
      substituents is reported. N-Alkylation, deprotonation and metalation with CuI
      /AgI /AuI synthons affords the heteroleptic triazolylidene complexes. Due to the
      combination of neutral, electron-donating ferrocenyl substituents and cationic,
      strongly electron-withdrawing cobaltocenium substituents, the mesoionic carbene
      (MIC) ligands of these complexes are electronically interesting "push-pull",
      "pull-push" and "pull-pull" metalloligands with further switchable redox states
      based on their fully reversible FeII /FeIII , (ferrocene/ferrocenium) and CoIII
      /CoII , (cobaltocenium/cobaltocene) redox couples. These are the first examples
      of metal complexes of (di)cationic NHC ligands based on cobaltoceniumyl
      substituents. DFT calculated Tolman electronic parameter (TEP) of the new MIC
      ligands, show these metalloligands to be extremely electron-poor NHCs with
      properties unmatched in other carbene chemistry. Utilization of these
      multimetallic electronically tunable compounds in catalytic oxazoline synthesis
      and in antitumor studies are presented. Remarkably, 1 mol % of the AuI complex
      with the dicationic MIC ligand displays full catalytic conversion, without the
      need for any other additives, in less than 2 hours at ambient temperatures. These
      results thus firmly establish these new classes of cobaltoceniumyl based
      (di)cationic MIC ligands as prominent players in several branches of chemistry.

PMID- 29214678
TI  - Pedicled iliac crest bone flap transfer for the treatment of upper femoral shaft
      fracture nonunion: An anatomic study and clinical applications.
AB  - PURPOSE: We present the results of a study on the anatomy of the ascending branch
      of the lateral circumflex femoral artery (AB-LCFA) and the use of the pedicled
      iliac bone flap transfer perfused by AB-LCFA combined with external fixation for
      the treatment of the nonunion of upper femoral shaft fractures. METHODS: The
      orientation, diameter, length, and distribution of the AB-LCFA from 40 lower
      limbs of adult cadavers were dissected and measured. From 2000 to 2012, 13
      patients with nonunion of upper femoral shaft fractures underwent pedicled iliac
      bone flap transfer perfused by the AB-LCFA combined with external fixation. The
      time of bone fracture union was recorded based on X-ray examination. The
      functional results of the femoral shaft were evaluated by the Klemm
      classification. RESULTS: The lateral circumflex femoral artery (LCFA) divided
      into ascending, transverse, and descending branches in 32 specimens (80%). The
      diameter of the AB-LCFA at the origin was 3.15 +/- 0.9 mm and the length of the
      AB-LCFA was 8.51 +/- 3.06 cm. The postoperative course of the procedure was
      uneventful in all 13 patients. The average follow-up was 15 months. Bone union
      was achieved in all patients and the average union time was 5.3 months. 12
      patients achieved excellent or good functional results based on the Klemm
      classification. CONCLUSION: The AB-LCFA has a consistent orientation and abundant
      blood flow. The transfer of the iliac crest bone flap perfused by the AB-LCFA
      while combined with external fixation could be an option for treating the
      nonunion of upper femoral shaft fractures.

PMID- 29214679
TI  - The relationship between negative metacognitive thoughts, pain catastrophizing
      and adjustment to chronic pain.
AB  - BACKGROUND: Cognitive appraisals, most notably pain catastrophizing, play an
      important role in chronic pain. The role of metacognition and its impact on the
      relationship between pain catastrophizing and health are understudied. The
      identification of metacognition as a moderator of psychological constructs may
      have clinical and empirical implications. We hypothesized that negative
      metacognitive beliefs would moderate the relationships between pain
      catastrophizing and emotional functioning and physical activity. METHOD:
      Participants (N = 211) with mixed aetiology chronic pain were primarily Caucasian
      females with severe average pain intensity. Over the course of 2 weeks,
      participants completed online daily-diary measures of pain catastrophizing, pain
      intensity, mood, physical activity and metacognition. RESULTS: Participants with
      higher average levels of daily pain intensity and negative metacognitive beliefs
      about worry reported higher levels of daily pain catastrophizing, as well as
      daily depression, and anxiety. Some aspects of metacognitive beliefs (i.e.
      dangerousness and uncontrollability of thoughts) were also negatively associated
      with average daily levels of positive affect. However, these effects were not
      interactive; metacognitive beliefs did not moderate the relationships of pain
      catastrophizing with other daily variables. CONCLUSIONS: From a daily coping
      perspective, findings reveal that people with stronger negative metacognitive
      beliefs report greater emotional distress on a day-to-day basis. However,
      negative metacognitive beliefs did not appear to modify the effects of pain
      catastrophizing on psychological and physical functioning at the daily level,
      suggesting that metacognitive beliefs may be better conceptualized as a more
      parallel indicator of emotional maladjustment to chronic pain whose effects do
      not reliably manifest in daily measurement models. SIGNIFICANCE: Findings
      highlight the need to better characterize the value of metacognitive beliefs as
      an important predictor and therapeutic target. Despite limited evidence of a
      dynamic relationship between metacognition and daily adjustment to chronic pain,
      results emphasize the potential importance of interventions that target cognitive
      appraisal process beyond catastrophizing, including uncontrollability and danger
      laden thought patterns.

PMID- 29214680
TI  - Flexible Bonding of the Phosph(V)azane Dianions [S(E)P(MU-NtBu)]22.
AB  - Oxidation of the PIII dianion [S-P(MU-NtBu)]22- (1) with elemental sulphur,
      selenium and tellurium gives the PV dianions [(S)(E)P(MU-NtBu)]22- (E = S (6 a),
      Se (6 b), Te (6 c)). Although 6 c proves to be too unstable, the S,S-dianion 6 a
      and ambidentate S,Se-dianion 6 b are readily transferred intact to main group and
      transition metal elements, producing a range of new cage and coordination
      compounds. While their coordination characteristics are in many ways similar to
      closely-related isoelectronic phosph(V)azane anions [(E)(RN=)P(MU-NtBu)]22- , the
      sterically unhindered nature of 6 introduces an expanded range of coordination
      modes, that is, facial S,S- and Se,Se-bonding as well as side-on S,Se
      coordination. All of these bonding modes are observed for the amibidentate S,Se
      dianion 6 b.

PMID- 29214681
TI  - Thyroid hormones alter estrous cyclicity and antioxidative status in the ovaries
      of rats.
AB  - To expand our understanding of the roles of thyroid hormones on female
      reproduction, we induced hypo- and hyper-T rat models to investigate the roles of
      thyroid hormones on estrous cyclicity, as well as the antioxidative status in the
      ovaries of rats. In the current study, our data show that hypothyroidism (hypo-T)
      and hyperthyroidism (hyper-T) led to significantly reduced body weights and
      ovarain weights and delayed vaginal opening day. For hyper-T, thyroxine (T4), tri
      iodothyronine (T3), progesterone (P4) and follicle-stimulating hormone (FSH) were
      significantly increased, while estradiol (E2) and luteinizing hormone (LH) were
      significantly decreased. For hypo-T rats, serum levels of total T4 and T3, E2,
      P4, FSH and LH were significantly increased, while concentrations of E2 and LH
      were significantly decreased. For ovary morphology, the numbers of secondary and
      antral follicles were significantly decreased with more atretic antral follicles
      and less corpora lutea in both hyper- and hypo-T groups. Both hyper-T and hypo-T
      treatment significantly decreased the expressions of thyroid hormone receptor
      alpha1 in the ovary. Hypo-T significantly reduced nitric oxide (NO), total NO
      synthase (tNOS), inducible NOS and constitutive NOS activities, but hyper-T
      increased them. For antioxidative parameters, hypo-T and hyper-T treatment
      significantly increased malondialdehyde (MDA) contents. The activities of both
      glutathione peroxidase (GSH-Px) and catalase (CAT) significantly decreased in the
      hypo-T group but increased in the hyper-T group. Total superoxide dismutase (T
      SOD) activity was significantly increased in the hyper-T group. In summary,
      thyroid hormones alter estrous cyclicity and antioxidative status in the ovary of
      the rat may act through the NOS signaling pathway.

PMID- 29214682
TI  - Attentional asymmetry between visual hemifields is related to habitual direction
      of reading and its implications for debate on cause and effects of dyslexia.
AB  - A major controversy regarding dyslexia is whether any of the many visual and
      phonological deficits found to be correlated with reading difficulty cause the
      impairment or result from the reduced amount of reading done by dyslexics. We
      studied this question by comparing a visual capacity in the left and right visual
      hemifields in people habitually reading scripts written right-to-left or left-to
      right. Selective visual attention is necessary for efficient visual search and
      also for the sequential recognition of letters in words. Because such attentional
      allocation during reading depends on the direction in which one is reading,
      asymmetries in search efficiency may reflect biases arising from the habitual
      direction of reading. We studied this by examining search performance in three
      cohorts: (a) left-to-right readers who read English fluently; (b) right-to-left
      readers fluent in reading Farsi but not any left-to-right script; and (c)
      bilingual readers fluent in English and in Farsi, Arabic, or Hebrew. Left-to
      right readers showed better search performance in the right hemifield and right
      to-left readers in the left hemifield, but bilingual readers showed no such
      asymmetries. Thus, reading experience biases search performance in the direction
      of reading, which has implications for the cause and effect relationships between
      reading and cognitive functions.

PMID- 29214683
TI  - Queer reproduction revisited and why race, class and citizenship still matters: A
      response to Cristina Richie.
AB  - In the dialogue between Timothy F. Murphy and Cristina Richie about queer
      bioethics and queer reproduction in this journal, significant points of the
      emergent and extremely important discussions on lesbian, gay, bisexual,
      transgender (LGBT) and queer bioethics are raised. Richie specifies correctly
      that queer bioethics can either complement or contradict LGBT bioethics and the
      queer standpoint against heteroconformity and heterofuturity is decisive here. As
      the field of queer bioethics is such a recent and essential part of consideration
      for bioethics and as it is still evolving, the objective of this intervention is
      to provide both an overview of important milestones of queer bioethics and to
      highlight that queer bioethics is not mono-logic and monolithic. To exemplify
      queer bioethic's 'many-headed monsters', queer reproduction is revisited and
      complemented by a European viewpoint. It is central to my argument and here I
      disagree with Richie that to be against heterofuturity does not necessarily mean
      to be against queer reproduction. However, I also argue that there are other
      reasons why queer reproduction should not be pursued at all costs. Finally, I
      discuss the most recent debates on race, class and citizenship, for example,
      queer necropolitics. These points still need to be addressed in queer bioethical
      agendas.

PMID- 29214684
TI  - Pharmacotherapies for apnoea of prematurity: time to pause and consider targeted
      sex-specific strategies?

PMID- 29214685
TI  - Exploring relationships between first-line nurse manager's safety attitudes and
      safety factors in Henan, China.
AB  - AIM: To examine first-line nurse managers' perceptions of safety culture and
      explore relationships between their safety attitudes and safety factors in Henan
      Province, China. BACKGROUND: Health providers' perceptions of patient safety
      culture have been studied widely, but little is known about first-line nurse
      managers' safety attitudes. METHODS: A cross-sectional survey was conducted with
      a convenience sample of 823 first-line nurse managers in 216 hospitals across
      Henan Province, China. The Safety Attitudes Questionnaire (Chinese version) was
      distributed to first-line nurse managers during training meetings; responses were
      returned in a sealed envelope in person or by mail. ANOVAs were used to analyse
      the differences in Safety Attitudes Questionnaire (Chinese version) scores
      between first-line nurse managers' attitudes and safety factors. RESULTS: The
      mean scores across the six domains of Safety Attitudes Questionnaire (Chinese
      version) ranged from 56.6 to 79.4 on a 100-point scale. First-line nurse
      managers: >=45 years of age perceived better safety climate (p < .05); those with
      higher professional ranks and medical centre positions reported higher mean
      scores for teamwork climate (p < .01) and stress recognition (p < .01); and those
      with baccalaureate degrees or higher had significantly higher mean scores for
      stress recognition (p < .01). CONCLUSION: First-line nurse managers' safety
      attitudes were not satisfactory and there is great potential to improve patient
      safety culture. Age, hospital level, educational background and professional rank
      are positively related to first-line nurse managers' attitudes. IMPLICATIONS FOR
      NURSING MANAGEMENT: Hospital administrators and nurse directors should focus on
      the safety factors identified in this study and enact a variety of strategies to
      create a strong patient safety culture in China.

PMID- 29214686
TI  - Myricetin attenuated LPS induced cardiac injury in vivo and in vitro.
AB  - Sepsis induced myocardial dysfunction (SIMD) is a common complication and leads
      to an increased mortality. SIMD is closely related to inflammation and oxidative
      stress. Myricetin exhibits strong capacities of anti-inflammation and anti
      oxidative stress, but its pharmacological effects for lipopolysaccharide (LPS)
      induced cardiac injury remains undefined. This study aimed to explore whether
      myricetin was efficient to alleviate SIMD in mice and neonatal rat cardiomyocytes
      injury. Mice administrated with myricetin (100 mg/kg, po, bid) or vehicle groups
      were challenged with LPS (10 mg/kg, ip), and cardiac functions examined by
      echocardiography after 12 hr LPS exposure. LPS markedly impaired mouse cardiac
      functions, which were significantly attenuated by myricetin administration.
      Myricetin significantly reduced the production of inflammatory cytokines both in
      serum and cardiac tissue. Myricetin could inhibit the nuclear translocation of
      p65, degradation of IkappaBalpha, and cellular apoptosis in vivo and in vitro.
      Myricetin also prevented overexpression of iNOS and reduction of oxidoreductase
      (SOD and GPx) activity. Besides, Myricetin treatment could attenuate production
      of inflammatory cytokines of peritoneal macrophages stimulated with LPS in vitro.
      Thus we concluded that myricetin could attenuate the LPS induced cardiac
      inflammation injury in vivo and in vitro. Myricetin may be a potential therapy or
      adjuvant therapy for SIMD.

PMID- 29214687
TI  - Urban-rural differences in health literacy and its determinants in Iran: A
      community-based study.
AB  - OBJECTIVE: Previous studies have shown a remarkable difference in functional
      health literacy among residents of urban and rural areas which may be attributed
      to socioeconomic inequalities between these areas. The aim of this study was to
      investigate the differences (if any) in the level of functional health literacy
      and its determinants between urban and rural areas in Sanandaj, Iran. DESIGN: A
      descriptive analytical cross-sectional study. PARTICIPANTS: A multistage
      clustered random sample of 1000 respondents older than 18 years. In total, 892
      respondents (response rate = 89.2%) completed test of functional health literacy
      in adults questionnaire through personal home-based interviews. Applying SPSS v.
      16, a series of anova, t-test and logistic regression tests were conducted. MAIN
      OUTCOME MEASURES: Inadequate/marginal functional health literacy. RESULTS:
      Respondents residing in rural areas having a diploma education and lower, with no
      history of hospitalisation, with monthly income <US$ 165 and being diagnosed with
      a chronic disease had significantly higher rates of inadequate/marginal
      functional health literacy. Among rural, but not urban, residents having a
      history of hospitalisation, a university education and a higher monthly income
      increased the odds of adequate functional health literacy by 1.84, 2.29 and 1.95
      times, respectively. CONCLUSIONS: The rural area residents suffered more from low
      functional health literacy, compared with their urban counterparts. Health
      literacy as a determinant of health and social welfare should be focused on with
      more detail by health decision-makers.

PMID- 29214688
TI  - Nootkatone confers hepatoprotective and anti-fibrotic actions in a murine model
      of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis.
AB  - In this study, the hepatoprotective and anti-fibrotic actions of nootkatone (NTK)
      were investigated using carbon tetrachloride (CCl4 )-induced liver fibrosis in
      mice. CCl4 administration elevated serum aspartate and alanine transaminases
      levels, respectively. In addition, CCl4 produced hepatic oxidative and nitrative
      stress, characterized by diminished hemeoxygenase-1 expression, antioxidant
      defenses, and accumulation of 4-hydroxynonenal and 3-nitrotyrosine. Furthermore,
      CCl4 administration evoked profound expression of pro-inflammatory cytokine
      expressions such as tumor necrosis factor-alpha, monocyte chemoattractant protein
      1, and interleukin-1beta in hepatic tissues, which corroborated with nuclear
      factor kappaB activation. Additionally, CCl4 -treated animals exhibited higher
      apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and
      poly (ADP-ribose) polymerase activation. Moreover, histological and biochemical
      investigations revealed marked fibrosis in the livers of CCl4 -administered
      animals. However, NTK treatment mitigated CCl4 -induced phenotypic changes. In
      conclusion, our findings suggest that NTK exerts hepatoprotective and anti
      fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.

PMID- 29214689
TI  - Distinct factors determine the kinetics of disease relapse in adults transplanted
      for acute myeloid leukaemia.
AB  - BACKGROUND: Disease recurrence remains the major cause of death in adults with
      acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or
      allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of
      maintenance drug or cellular therapies represent emerging strategies with the
      potential to reduce relapse after both treatment modalities, but whilst the
      determinants of overall relapse risk have been extensively characterized the
      factors determining the timing of disease recurrence have not been characterized.
      MATERIALS AND METHODS: We have therefore examined, using a series of sequential
      landmark analyses, relapse kinetics in a cohort of 2028 patients who received an
      allo-SCT for AML in CR1 and separately 570 patients treated with IC alone.
      RESULTS: In the first 3 months after allo-SCT, the factors associated with an
      increased risk of relapse included the presence of the FLT3-ITD (P < 0.001),
      patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and
      donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher
      white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001),
      presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first
      complete remission (P = 0.013). Later relapse was associated with adverse
      cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD)
      and the use of in vivo T-cell depletion. In patients treated with IC alone, the
      factors associated with relapse in the first 3 months were adverse-risk
      cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting
      later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time
      interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together,
      these data provide novel insights into the biology of disease recurrence after
      both allo-SCT and IC and have the potential to inform the design of novel
      maintenance strategies in both clinical settings.

PMID- 29214691
TI  - Photoactive plants: Botany bad boys or horticultural heroes?

PMID- 29214690
TI  - alpha-Lipoic acid inhibits testicular and epididymal oxidative damage and
      improves fertility efficacy in arsenic-intoxicated rats.
AB  - The present study evaluates the protective effect of alpha-lipoic acid (LA)
      against arsenic-induced testicular and epididymal oxidative damage in rats.
      Arsenic caused significant reduction in the reproductive organ weights, serum
      testosterone levels, testicular daily sperm count, epididymal sperm count, sperm
      motility, sperm viability, and sperm membrane integrity. Significant reduction in
      the activity levels of superoxide dismutase, catalase, and glutathione levels
      with a concomitant increase in the lipid peroxidation and protein carbonyl
      content in the testis and the cauda epididymis of arsenic-exposed rats. Arsenic
      intoxication also enhanced the testicular caspase-3 mRNA levels, disorganization
      of testicular and cauda epididymal architecture as well as increased arsenic
      content in the testis and the cauda epididymis of rats. Arsenic exposure also
      deteriorated fertility ability in male rats over controls. Conversely, alpha-LA
      negated the testicular and cauda epididymal oxidative stress and restored the
      male reproductive health in arsenic-exposed rats.

PMID- 29214692
TI  - Cryo-EM Revolutionizes the Structure Determination of Biomolecules.
AB  - Freeze frame: The Nobel Prize in Chemistry 2017 was jointly awarded to Jacques
      Dubochet, Joachim Frank, and Richard Henderson for "developing cryo-electron
      microscopy (cryo-EM) for the high-resolution structure determination of
      biomolecules in solution". This Highlight describes how the field of cryo-EM
      developed from the first transmission electron microscope in 1931 to the
      sophisticated technique of today.

PMID- 29214693
TI  - Characterization of myofibrillar adenosine triphosphatase activity and liberation
      of actin from myofibrils upon heating chicken breast meat.
AB  - Denaturation of actin and myosin in myofibrils induced by heating at 50 degrees C
      was investigated to reveal the mechanism of irreversible liberation of actin from
      myofibrils on heating at lower temperatures than conventional cooking.
      Denaturation of these proteins was determined by Mg2+ -ATPase (adenosine
      triphosphatase) and Ca2+ -ATPase activities. When minced meat was heated for 20
      min, actin was liberated accompanying denaturation of 80% of actin and 50% of
      myosin. Heating of the myofibrillar fraction (MFF) isolated from meat homogenate
      induced much slower denaturation of actin than myosin. When MFF was heated with
      sarcoplasmic fractions, denaturation of actin was facilitated, suggesting that
      sarcoplasmic fractions contain factors to facilitate actin denaturation. Inosine
      5'-monophosphate, a component of sarcoplasmic fractions, was shown to have no
      effect on actin and myosin denaturation. These results suggest that heating meat
      at 50 degrees C dissociates binding ('Bond A') between actin and myosin
      participating in ATPase activities, resulting in denaturation of both proteins
      under influence of sarcoplasmic components. Although denaturation of actin and
      myosin disrupted Bond A, actin was not liberated simultaneously, suggesting the
      presence of another bond ('Bond B', more heat-stable than Bond A) between both
      proteins and necessity of disruption of Bond B for actin release from myofibrils.

PMID- 29214694
TI  - Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and
      management.
AB  - DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous
      group of myeloid disorders characterized by peripheral blood cytopenias and
      increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs
      more frequently in older males and in individuals with prior exposure to
      cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence
      of dysplasia upon visual examination of a bone marrow aspirate and biopsy.
      Information obtained from additional studies such as karyotype, flow cytometry or
      molecular genetics is usually complementary and may help refine diagnosis. RISK
      STRATIFICATION: Prognosis of patients with MDS can be calculated using a number
      of scoring systems. In general, all these scoring systems include analysis of
      peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic
      characteristics. The most commonly used system is probably the International
      Prognostic Scoring System (IPSS). IPSS is now replaced by the revised IPSS-R
      score. Although not systematically incorporated into new validated prognostic
      systems, somatic mutations can help define prognosis and should be considered as
      new prognostic factors. RISK-ADAPTED THERAPY: Therapy is selected based on risk,
      transfusion needs, percent of bone marrow blasts and cytogenetic and mutational
      profiles. Goals of therapy are different in lower risk patients than in higher
      risk. In lower risk, the goal is to decrease transfusion needs and transformation
      to higher risk disease or AML, as well as to improve survival. In higher risk,
      the goal is to prolong survival. Current available therapies include growth
      factor support, lenalidomide, hypomethylating agents, intensive chemotherapy and
      allogeneic stem cell transplantation. The use of lenalidomide has significant
      clinical activity in patients with lower risk disease, anemia and a chromosome 5
      alteration. 5-azacitidine and decitabine have activity in both lower and higher
      risk MDS. 5-azacitidine has been shown to improve survival in higher risk MDS. A
      number of new molecular lesions have been described in MDS that may serve as new
      therapeutic targets or aid in the selection of currently available agents.
      Additional supportive care measures may include the use of prophylactic
      antibiotics and iron chelation. MANAGEMENT OF PROGRESSIVE OR REFRACTORY DISEASE:
      At the present time there are no approved interventions for patients with
      progressive or refractory disease particularly after hypomethylating based
      therapy. Options include participation in a clinical trial or cytarabine based
      therapy and stem cell transplantation.

PMID- 29214695
TI  - Psoriasis improvement after gastric bandage in a patient partial responder to
      infliximab.
AB  - Patients overweight or obese have more severe psoriasis than normal weight
      patients. Sometimes the excessive weight is related to a lack of efficacy of
      systemic treatment. We report a case of a psoriatic patient that experienced a
      dramatic improvement of psoriasis after weight loss surgery by gastric bandage.
      The great weight loss was accompanied by an effectiveness gain of response to
      infliximab. The mechanism responsible for this association is not certain, but it
      is probably multifactorial, involving genetic, environmental and immune-mediated
      factors. It has been suggested that adipose tissue can dramatically alter the
      volume of drug distribution and limit drug efficacy. Moreover, a reduction of
      weight could favour the response to therapy and remission of the disease,
      inducing an improvement in patient's quality of life. Gastric bandage has a
      scarce rate of complications, a fast recovery and scarce life-threatening
      complications. It should be considered in obese patient that not shown
      effectiveness to therapy.

PMID- 29214696
TI  - Microemulsions, Micelles, and Functional Gels: How Colloids and Soft Matter
      Preserve Works of Art.
AB  - Colloid science provides fundamental knowledge to fields such as the
      pharmaceutical, detergency, paint, and food industry. An exciting application is
      art conservation, which poses a challenge owing to the complex range of
      interfacial interactions involved in restoring artefacts. Currently, the majority
      of the most performing and environmentally safe cleaning and consolidation agents
      for artworks belong to soft matter and colloids. The development and application
      of increasingly complex systems, from microemulsions to semi-interpenetrating
      hydrogels containing such fluids, is presented. These systems have been used on
      diverse artefacts, from Renaissance frescos to works by Picasso and Pollock.
      Chemical design can be implemented to meet the requirements of curators, and
      knowledge of the colloid structure and dynamics can overcome serendipitous
      approaches of traditional conservation practice. Future perspectives for soft
      matter and colloid science in the field of cultural heritage preservation are
      also summarized.

PMID- 29214697
TI  - Incorporation of 2,6-Connected Azulene Units into the Backbone of Conjugated
      Polymers: Towards High-Performance Organic Optoelectronic Materials.
AB  - Azulene is a promising candidate for constructing optoelectronic materials. An
      effective strategy is presented to obtain high-performance conjugated polymers by
      incorporating 2,6-connected azulene units into the polymeric backbone, and two
      conjugated copolymers P(TBAzDI-TPD) and P(TBAzDI-TFB) were designed and
      synthesized based on this strategy. They are the first two examples for 2,6
      connected azulene-based conjugated polymers and exhibit unipolar n-type
      transistor performance with an electron mobility of up to 0.42 cm2  V-1  s-1 ,
      which is among the highest values for n-type polymeric semiconductors in bottom
      gate top-contact organic field-effect transistors. Preliminary all-polymer solar
      cell devices with P(TBAzDI-TPD) as the electron acceptor and PTB7-Th as the
      electron donor display a power conversion efficiency of 1.82 %.

PMID- 29214698
TI  - Heart transplantation turns 50 and is going strong.

PMID- 29214699
TI  - Lithium: The silver lining to clouded thinking?

PMID- 29214700
TI  - Adaptive behaviour, executive function and employment in adults with Down
      syndrome.
AB  - BACKGROUND: Individuals with Down syndrome (DS) demonstrate difficulties with
      aspects of executive function (EF) and adaptive behaviour across the lifespan.
      There is a current lack of information regarding how these difficulties relate to
      employment outcomes in adulthood. This study evaluated the adaptive behaviour and
      EF profiles of individuals with DS during early adulthood and the association
      between these areas of functioning and employment status. METHODS: Parents or
      caregivers of primarily young adults with DS (n = 31; mean chronological age =
      25.9 years; SD = 5.92) completed the Vineland Adaptive Behavior Scales - Second
      Edition the Behavior Rating Inventory of Executive Function - Adult version and a
      demographic questionnaire that requested information regarding adult employment
      status. RESULTS: Findings indicated a distinct pattern of relative strengths and
      challenges in adaptive behaviour and EF. In addition, the EF sub-domain of
      working memory was a significant predictor of employment status. CONCLUSIONS:
      Specific aspects of the DS cognitive profile may have an important influence on
      employment status in primarily young adults with DS. Implications for
      interventions are discussed.

PMID- 29214701
TI  - A population-based, cross-sectional study of the prevalence and correlates of
      sedentary behaviour of adults with intellectual disabilities.
AB  - BACKGROUND: High levels of sedentary behaviour have a negative impact on health
      and well-being. There is limited evidence on the prevalence and correlates of
      sedentary behaviour of adults with intellectual disabilities (ID). METHODS: A
      population-based sample of adults with ID were invited to take part in a
      comprehensive health check programme. Demographic and health data were collected
      during a structured interview and physical examination. Screen time was used as a
      proxy measure of sedentary behaviour. Bivariate and multivariate statistical
      modelling examined correlates of screen time. RESULTS: Fifty per cent of the 725
      participants reported four or more hours of screen time per day. Male gender,
      higher levels of intellectual ability, mobility problems, obesity, not having
      hearing impairment and not having epilepsy were all significantly associated with
      higher screen time in the final multivariate model (R2  = 0.16; Hosmer-Lemeshow
      goodness of fit statistic P = 0.36). CONCLUSIONS: This is the first study to
      publish population-based data on the prevalence and correlates of sedentary
      behaviour in adults with ID. Compared with adults who do not have ID, adults with
      ID have higher levels, and different correlates, of sedentary behaviour. A better
      understanding of the social context of sedentary behaviour will inform the design
      of effective behaviour change programmes for adults with ID.

PMID- 29214702
TI  - Skin injuries and joint contractures of the upper extremities in Rett syndrome.
AB  - OBJECTIVES: The purpose of this study was to investigate the incidence and type
      of skin injuries and joint contractures of the upper extremities in individuals
      with Rett syndrome. METHODS: In 2016, a questionnaire regarding skin injuries and
      joint contractures was sent to 1016 directors of schools for special needs
      education and 204 directors of departments of rehabilitation [consisting of 130
      facilities for persons with severe motor and intellectual disabilities (SMID), 73
      wards for patients with SMID, and the National Hospital Organisation and National
      Centre Hospital, National Centre of Neurology and Psychiatry] in Japan.
      Descriptive statistics were used to indicate frequency in each question. RESULTS:
      Information was acquired from 216 cases (3-53 years old) with Rett syndrome. Skin
      injuries and joint contractures of the upper extremities were observed in 41% and
      49% of individuals with Rett syndrome, respectively. Most of the skin injuries
      were observed on the hands (19%) and fingers (29%). The incidence of skin
      injuries was not affected by age or disease severity. Many joint contractures
      were observed in the shoulder (33%) and elbow (29%) joints. Joint contractures
      tended to occur in individuals aged over 10 years or with severe locomotor
      impairment. CONCLUSION: Almost half of the Rett syndrome subjects assessed in the
      present study had skin injuries and joint contractures. Especially, the incidence
      of joint contractures was affected by age and disease severity. Thus, it is
      important that medical staff attempt to prevent the occurrence of skin injuries
      and joint contractures in this patient population.

PMID- 29214703
TI  - Corrigendum.

PMID- 29214704
TI  - Definition of the term "mood stabilizer".

PMID- 29214705
TI  - A Visible-Light-Driven Iminyl Radical-Mediated C-C Single Bond Cleavage/Radical
      Addition Cascade of Oxime Esters.
AB  - A room-temperature, visible-light-driven N-centered iminyl radical-mediated and
      redox-neutral C-C single bond cleavage/radical addition cascade reaction of oxime
      esters and unsaturated systems has been accomplished. The strategy tolerates a
      wide range of O-acyl oximes and unsaturated systems, such as alkenes, silyl enol
      ethers, alkynes, and isonitrile, enabling highly selective formation of various
      chemical bonds. This method thus provides an efficient approach to various
      diversely substituted cyano-containing alkenes, ketones, carbocycles, and
      heterocycles.

PMID- 29214706
TI  - Growth performance, carcass traits and meat quality of yellow-feathered broilers
      fed graded levels of alfalfa meal with or without wheat.
AB  - The effects of 0, 40 and 80 g/kg alfalfa meal on growth performance, carcass
      traits and meat quality of Chinese yellow-feathered broilers fed diets containing
      or lacking wheat (0 or 200 g/kg) as part of the energy source, were examined
      using random design with a 2 * 3 factorial arrangement of treatments. Dressing
      percentage and semi-eviscerated proportion were lower, and meat color a*
      (redness) value was higher in birds fed diets containing wheat than diets lacking
      wheat (P < 0.05). Drip loss was reduced by the addition of alfalfa meal to diets
      containing or lacking wheat (P < 0.05). Average sensory score of breast meat was
      higher in chickens fed corn-based diets than in those fed wheat (P < 0.05). Meat
      from those supplemented with 40 g/kg alfalfa meal had better taste than the other
      two levels (P < 0.05). The inclusion of wheat significantly reduced the
      activities of creatine kinase and calpain of breast muscle (P < 0.05). In
      conclusion, Chinese yellow-feathered broilers fed diets containing wheat had
      better meat color and lower drip loss than those fed the diets without wheat, and
      adding 40 g/kg alfalfa meal generally improved meat quality and taste.

PMID- 29214707
TI  - Movement decline across lifespan of Caenorhabditis elegans mutants in the
      insulin/insulin-like signaling pathway.
AB  - Research in aging biology has identified several pathways that are molecularly
      conserved across species that extend lifespan when mutated. The insulin/insulin
      like signaling (IIS) pathway is one of the most widely studied of these. It has
      been assumed that extending lifespan also extends healthspan (the period of life
      with minimal functional loss). However, data supporting this assumption conflict
      and recent evidence suggest that life extension may, in and of itself, extend the
      frail period. In this study, we use Caenorhabditis elegans to further probe the
      link between lifespan and healthspan. Using movement decline as a measure of
      health, we assessed healthspan across the entire lifespan in nine IIS pathway
      mutants. In one series of experiments, we studied healthspan in mass cultures,
      and in another series, we studied individuals longitudinally. We found that long
      lived mutants display prolonged mid-life movement and do not prolong the frailty
      period. Lastly, we observed that early-adulthood movement was not predictive of
      late-life movement or survival, within identical phenotypes. Overall, these
      observations show that extending lifespan does not prolong the period of frailty.
      Both genotype and a stochastic component modulate aging, and movement late in
      life is more variable than early-life movement.

PMID- 29214708
TI  - Photocontrolled Release of Chemicals from Nano- and Microparticle Containers.
AB  - A benzoin-derived diol linker was synthesized and used to generate biocompatible
      polyesters that can be fully decomposed on demand upon UV irradiation. Extensive
      structural optimization of the linker unit was performed to enable the defined
      encapsulation of diverse organic compounds in the polymeric structures and allow
      for a well-controllable polymer cleavage process. Selective tracking of the
      release kinetics of encapsulated model compounds from the polymeric nano- and
      microparticle containers was performed by confocal laser scanning microscopy in a
      proof-of-principle study. The physicochemical properties of the incorporated and
      released model compounds ranged from fully hydrophilic to fully hydrophobic. The
      demonstrated biocompatibility of the utilized polyesters and degradation products
      enables their use in advanced applications, for example, for the smart packaging
      of UV-sensitive pharmaceuticals, nutritional components, or even in the area of
      spatially selective self-healing processes.

PMID- 29214709
TI  - Imaging of the lamina cribrosa and its role in glaucoma: a review.
AB  - The lamina cribrosa of the optic nerve head serves two contrasting roles; it must
      be porous to allow retinal ganglion cell axons to pass through, and yet at the
      same time, it must also provide adequate structural support to withstand the
      stresses and strains across it. Improvements in imaging such as optical coherence
      tomography image capture and image processing have allowed detailed in vivo
      studies of lamina cribrosa macro- and micro-architectural characteristics. This
      has aided our understanding of the optic nerve head as a complex biomechanical
      structure. In this review, we first aim to frame the biomechanical considerations
      of lamina cribrosa in a clinical context; in doing so, we also explore the
      concept of the translaminar pressure difference. Second, we aim to highlight the
      technological advances in imaging the lamina cribrosa and its accompanying
      clinical implications, and future directions in this quickly progressing field.

PMID- 29214710
TI  - A research team's perspective on the editorial 'Revolutionary reform in
      psychiatric care in Italy: the abolition of forensic mental hospitals'.

PMID- 29214711
TI  - Section 44: Is this provision in mental health legislation in England and Wales
      obsolete?

PMID- 29214712
TI  - Extended suicide: Public tragedy.

PMID- 29214713
TI  - Stent graft treatment for infra-inguinal arterial disease for either instent
      restenosis and denovo lesions associated with very high rates of failure.
AB  - BACKGROUND: FDA approved the Gore Viabahn (WL Gore, Flagstaff, AZ, USA) stent for
      both femoro-popliteal arterial denovo and instent restenosis (ISRS) lesions. To
      date there is little data on Viabahn stent graft outcomes in ISRS arterial
      disease. METHODS: Between 2007 and 2014 we identified 734 patients who underwent
      1573 endovascular interventions in our institution for infra-inguinal
      revascularization. Among these, 48 patients had 143 Viabahn stents placed. Of
      these, 26 patients had 94 stents placed for ISRS and 22 patients had 49 stents
      placed for denovo lesions. RESULTS: The patients in the ISRS group were younger
      and more likely to have hypertension, hyperlipidemia, coronary artery disease,
      compared to the patients in the denovo group. Stents were placed principally for
      femoro-popliteal lesions, with mean length of 21 +/- 12.5 cm (19.2 +/- 14, ISRS
      vs. 22.1 +/- 11, denovo; P = 0.2). Both groups had low primary patency rates
      during one year follow up (54% vs. 33%, OR = 2.3 (0.9-2.2). Target lesion
      revascularization (TLR) (57% vs. 27%, P < 0.0001, OR = 3.7, CI = 1.8-8) and
      surgical revascularization (21% vs. 4%, OR = 6.3, CI = 1.4-28) occurred more
      frequently in the ISRS group than in the denovo group. Amputation rate (17% vs.
      31%, OR 0.7, CI = 0.2-1), cumulative blockage (defined as ISRS and thrombosis)
      (62% vs. 47%, P = 0.09, OR = 1.8, CI = 0.9-3.6), and Restenosis (40% vs. 31%, OR
      1.5, CI = 0.7-3.2) were not statistically different between the two groups. Mean
      duration of follow-up was 12.8 +/- 13 months. CONCLUSION: Stent graft treatment
      using the Gore Viabahn for denovo and ISRS in femoro-popliteal arterial
      obstructive disease have high restenosis and failure rates, of both stent patency
      and limb outcomes, which is consistent with existed literature.

PMID- 29214714
TI  - Micromotion analysis of different implant configuration, bone density, and
      crestal cortical bone thickness in immediately loaded mandibular full-arch
      implant restorations: A nonlinear finite element study.
AB  - BACKGROUND: Excessive micromotion may cause failure of osseointegration between
      the implant and bone. PURPOSE: This study investigated the effects of implant
      configuration, bone density, and crestal cortical bone thickness on micromotion
      in immediately loaded mandibular full-arch implant restorations. MATERIALS AND
      METHODS: A finite element model of the edentulous mandible was constructed. Four
      implants were inserted in two different configurations, which were four parallel
      implants or tilted distal implants according to the all-on-four concept.
      Different cancellous bone densities and crestal cortical bone thicknesses were
      simulated. The framework was made of acrylic resin. A vertical load of 200 N was
      applied at the cantilever or on the distal implant (noncantilever loading).
      RESULTS: The maximum extent of micromotion was significantly influenced by the
      density of cancellous bone and to a lesser extent by implant configuration and
      the crestal cortical bone thickness. The all-on-four configuration showed less
      micromotion than the parallel implant configuration in some circumstances. The
      maximum micromotion detected with noncantilever loading was less than 1/3 of that
      with cantilever loading. CONCLUSIONS: Implant configuration had a limited
      influence on micromotion. Avoiding cantilever loading during the healing period
      should effectively reduce the risk of excessive micromotion in patients with low
      density cancellous bone and thin crestal cortical bone.

PMID- 29214715
TI  - Cutometric assessment of elasticity of skin with striae distensae following
      carboxytherapy.
AB  - OBJECTIVE: The aim of the study was to evaluate the effectiveness of
      carboxytherapy in the treatment of striae distensae. Additionally, discomfort and
      side effects associated with the treatment were assessed. MATERIALS AND METHODS:
      This study involved 15 women aged 22-40 years. They underwent 3 sessions of
      carboxytherapy at one-week intervals. Treatment was performed in skin area within
      stretch marks located on stomach, buttocks, and thighs. Cutometric probe was used
      to evaluate skin elasticity. Four measurements were performed-immediately before
      each treatment and one month after the last session. Photographic documentation
      was made before and after a series of treatment to perform clinical evaluation of
      changes in skin condition. RESULTS: Statistical analysis of results obtained with
      the use of Cutometer (R2 and R8 parameters) demonstrated that carboxytherapy
      significantly improved skin elasticity within stretch marks (P < .05). The
      analysis of photographic documentation revealed 58% improvement in stretch mark
      visibility. The width and length of stretch marks decreased, and their color
      became more like the natural color of the skin. Carboxytherapy is associated with
      moderate pain/discomfort. The occurrence of hematoma is the main side effect of
      this procedure. CONCLUSIONS: Carboxytherapy seems to be an effective method of
      reducing stretch marks. This procedure is safe, and it can be performed without
      the risk of complications. Moreover, it does not require special postoperative
      convalescence. Photographic documentation is a method of assessment of aesthetic
      procedures effectiveness, which is complementary to other objective methods (eg,
      the use of MPA probes).

PMID- 29214716
TI  - Psychometric assessment of the Spiritual Climate Scale Arabic version for nurses
      in Saudi Arabia.
AB  - AIM: To assess the psychometric properties of the Spiritual Climate Scale Arabic
      version for Saudi nurses. BACKGROUND: Evidence showed that a high level of
      spiritual climate in the workplace is associated with increased productivity and
      performance, enhanced emotional intelligence, organisational commitment and job
      satisfaction among nurses. METHOD: A convenient sample of 165 Saudi nurses was
      surveyed in this descriptive, cross-sectional study. Cronbach's alpha and
      intraclass correlation coefficient of the 2 week test-retest scores were computed
      to establish reliability. Exploratory factor analysis was performed to support
      the validity of the Spiritual Climate Scale Arabic version. RESULTS: The
      Spiritual Climate Scale Arabic version manifested excellent content validity.
      Exploratory factor analysis supported a single factor with an explained variance
      of 73.2%. The Cronbach's alpha values of the scale ranged from .79 to .88, while
      the intraclass correlation coefficient value was .90. The perceived spiritual
      climate was associated with the respondents' hospital, gender, age and years of
      experience. CONCLUSIONS: Findings of this study support the sound psychometric
      properties of the Spiritual Climate Scale Arabic version. IMPLICATIONS FOR
      NURSING MANAGEMENT: The Spiritual Climate Scale Arabic version can be used by
      nurse managers to assess the nurses' perception of the spiritual climate in any
      clinical area. This process can lead to spiritually centred interventions,
      thereby ensuring a clinical climate that accepts and respects different spiritual
      beliefs and practices.

PMID- 29214717
TI  - Bisphenol A is an exogenous toxin that promotes mitochondrial injury and death in
      tubular cells.
AB  - BACKGROUND: Uremic toxins that accumulate in chronic kidney disease (CKD)
      contribute to CKD complications, such as CKD progression. Bisphenol A (BPA) is a
      ubiquitous environmental toxin, structurally related with p-cresol, that
      accumulates in CKD. Our aim was to characterize the nephrotoxic potential of BPA.
      Specifically, we addressed BPA toxicity over energy-demanding proximal tubular
      cells. METHODS: Cell death and oxidative stress were evaluated by flow cytometry
      and confocal microscopy in HK-2 human proximal tubular epithelial cells.
      Functional assays tested ATP, intracellular Ca2+ , mitochondrial function
      (tetramethylrhodamine methyl [TMRM]), oxygen consumption, Nrf2-binding, MitoSOX,
      and NADPH oxidase activity. Gene expression was assessed by qRT-PCR. RESULTS:
      Following acute exposure (24 hours), proximal tubular cell viability was
      decreased by BPA concentrations >=50 MUM while a seven-day exposure resulted in a
      progressive loss of cell viability at a nanomolar range. Within 24 hours, BPA
      promoted mitochondrial dysfunction leading to energy depletion and increased
      mitochondrial and cytoplasmic oxidative stress and apoptosis in a concentration
      dependent manner. An antioxidant response was observed manifested by nuclear Nrf2
      translocation and increased expression of the Nrf2 target genes Heme oxygenase 1
      (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1). CONCLUSIONS: This study
      demonstrates for the first time that BPA causes mitochondrial injury, oxidative
      stress and apoptotic death in tubular cells. These results characterize BPA as an
      exogenous toxin that, similar to uremic toxins, may contribute to CKD
      progression.

PMID- 29214718
TI  - Coronary artery disease, revascularization, and clinical outcomes in
      transcatheter aortic valve replacement: Real-world results from the East Denmark
      Heart Registry.
AB  - Transcatheter aortic valve replacement (TAVR) has become an established
      therapeutic option for patients with symptomatic, severe aortic stenosis. The
      optimal treatment strategy for concomitant coronary artery disease (CAD) has not
      been tested prospectively in a randomized clinical trial. This study aimed to
      describe the degree of CAD, revascularization strategies, and long-term clinical
      outcomes in a large-scale all-comers TAVR-population. Nine hundred and forty-four
      consecutive patients underwent TAVR. Obstructive CAD was reported in 224 patients
      (23.7%)-of these, 150 (66.9%) presented with one-vessel disease (1-VD), 51
      (22.8%) with 2-VD, and 23 (10.3%) with 3-VD. Two-thirds underwent coronary
      revascularization before TAVR; half of those patients with 1-VD and only one
      third of those with multivessel disease were completely revascularized. In
      general, borderline stenoses (50%-70%) were more frequently revascularized in
      proximal coronary segments than in more distal segments. Long-term survival rates
      by Kaplan-Meier analysis of the total TAVR population at 5 and 9 years were 64.7%
      and 54.1%, respectively. A diagnostic coronary angiography was performed in 16.5%
      of patients within 5 years after TAVR; only 4.8% underwent consequent
      percutaneous coronary intervention (PCI). There was no difference in survival and
      need for revascularization post-TAVR between those patients with or without
      obstructive CAD +/- revascularization. Neither was there a survival difference
      between those with or without previous CABG and/or chronic total occlusion(s). In
      conclusion, CAD is prevalent in TAVR patients and pre-TAVR coronary
      revascularization is typically focused on treating proximal and high-grade
      stenosis. A selective pre-TAVR PCI strategy results in favorable clinical
      outcomes with very low rates of post-TAVR coronary revascularization.

PMID- 29214719
TI  - Ineffectiveness of infliximab CT-P13 for the treatment of scleromyxedema: A case
      report.

PMID- 29214720
TI  - Reliability of three questions for the screening of advanced cognitive impairment
      in polypathological patients.
AB  - AIM: To determine whether answering three questions erroneously ("what is the
      date today?," "when were you born?" and "how old are you?") allows for the
      detection of advanced cognitive impairment in polypathological patients. METHODS:
      A cross-sectional study of patients admitted to the internal medicine and
      geriatrics departments was carried out. Advanced cognitive impairment was
      diagnosed when patients made 7-10 errors in the Short Portable Mental Status
      Questionnaire. RESULTS: We included 441 polypathological patients, 330 of them
      from the internal medicine departments and 111 from the geriatrics department.
      Their mean age was 80.8 years (8.9 years). Of them, 141 (32.0%) answered one
      question incorrectly, 58 (13.1%) answered two and 89 (20.2%) answered all three
      questions incorrectly. The prevalence of advanced cognitive impairment was 27.7%.
      The sensitivity, specificity, and positive and negative predictive values of the
      test were 0.705, 0.991, 0.966 and 0.898, respectively. The accuracy of the test
      was 0.912. The area under the receiver operating characteristic curve was 0.947,
      95% CI 0.923-0.970. CONCLUSIONS: The three questions test has very good
      specificity and positive predictive value, and it can be used for the screening
      of advanced cognitive impairment in polypathological patients. Geriatr Gerontol
      Int 2018; 18: 441-447.

PMID- 29214721
TI  - Surface characterization of titanium implant healing abutments before and after
      placement.
AB  - BACKGROUND: Implant healing abutments (IHA) have a vital role in soft tissue
      healing after implant placement. Although there is thorough investigation on the
      implant surface, little is known about the effects potentially damaging oral
      conditions impose on healing abutments. PURPOSE: To characterize the surface of
      titanium healing abutments before and after clinical placement to understand the
      effects of the oral environment and time on the device surface. MATERIALS AND
      METHODS: Ten regular Straumann IHA were subjected to characterization pre and
      postplacement to elucidate the effects of the oral environment on device
      surfaces. Changes in surface crystallinity, morphology, and elemental composition
      were monitored with Raman spectroscopy, scanning electron microscopy, optical
      microscopy, and x-ray photoelectron spectroscopy, respectively. In addition,
      corrosion rate and polarization resistance were obtained to assess
      electrochemical device stability after placement. RESULTS: Control analysis
      indicated the titanium oxide of IHAs was thicker than natural commercially pure
      titanium and had the structure of crystalline anatase. After removal, the
      abutments possessed large amounts of biological debris, visible scratches, and
      discoloration sparsely on the surface. Spectroscopic analysis revealed the
      titanium oxide on the surface of IHAs was structurally unchanged, with
      crystalline titanium dioxide still present on the surface. Electrochemical
      results revealed that implanted healing abutments possessed a significantly
      higher corrosion rate than controls (change in corrosion rate = 2.34 +/- 0.58
      nm/year). CONCLUSIONS: Healing abutments were stable in the oral environment due
      to the chemical stability of the oxide, and were likely subjected to abrasions
      from unintentional loading and oral hygiene techniques.

PMID- 29214722
TI  - Boosting Electrochemical Water Oxidation with Metal Hydroxide Carbonate Templated
      Prussian Blue Analogues.
AB  - The development of efficient and stable catalyst systems with low-cost, abundant,
      and non-toxic materials is the primary demand for electrochemical water
      oxidation. A unique method is reported for the syntheses of metal hydroxide
      carbonate templated Prussian blue analogues (PBAs) on carbon cloth and their
      outstanding water oxidation activities in alkaline medium. The best water
      oxidation activity is obtained with cobalt hydroxide carbonate templated t-CoII 
      CoIII with an overpotential as low as 240 mV to reach a current density of 10 mA
      cm-2 . It produces constant current over 50 h in chronoamperometric measurements.
      Moreover, the catalysts outperform the activities of the PBAs prepared without
      any template and even the noble metal catalyst RuO2 . Spectroscopic and
      microscopic studies show that the PBAs are transformed into layered hydroxide
      oxyhydroxide structures during electrochemical process and provide the active
      sites for the water oxidation.

PMID- 29214724
TI  - CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide
      stimulated macrophages through ceramide-initiated protein phosphatase 2A
      activation.
AB  - CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis
      mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this
      study, other major attributes of CME-1, namely anti-inflammatory and
      immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)
      stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric
      oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME
      1-treated RAW 264.7 cells, LPS-induced IkappaBalpha degradation and the
      phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs),
      including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38,
      were reduced. Treatment with a protein phosphatase 2A (PP2A)-specific inhibitor,
      significantly reversed the CME-1-suppressed iNOS expression; IkappaBalpha
      degradation; and p65, Akt and MAPK phosphorylation. PP2A activity up-regulation
      and PP2A demethylation reduction were also observed in the cells. Moreover, CME-1
      induced PP2A activation and its subsequent suppression of LPS-activated RAW 264.7
      cells were diminished by the inhibition of ceramide signals. LPS-induced reactive
      oxygen species (ROS) and hydroxyl radical formation were eliminated by treating
      RAW 264.7 cells with CME-1. Furthermore, the role of ceramide signalling pathway
      and anti-oxidative property were also demonstrated in CME-1-mediated inhibition
      of LPS-activated primary peritoneal macrophages. In conclusion, CME-1 suppressed
      iNOS expression by up-regulating ceramide-induced PP2A activation and reducing
      ROS production in LPS-stimulated macrophages. CME-1 is a potential therapeutic
      agent for treating inflammatory diseases.

PMID- 29214725
TI  - Strictly Conserved Residues in Euphorbia tirucalli beta-Amyrin Cyclase: Trp612
      Stabilizes Transient Cation through Cation-pi Interaction and CH-pi Interaction
      of Tyr736 with Leu734 Confers Robust Local Protein Architecture.
AB  - The functions of Trp612, Leu734, and Tyr736 of Euphorbia tirucalli beta-amyrin
      synthase were examined. The aliphatic variants (Ala, Val, Met) of Trp612 showed
      almost no activity, but the aromatic variants exhibited high activities: 12.5 %
      of the wild-type activity for the W612H variant, 43 % for W612F, and 63 % for
      W612Y. That is, the enzymatic activities of the variants increased in proportion
      to the increase in pi-electron density. Thus, the major function of Trp612 is to
      stabilize transient cations through a cation-pi interaction. The Phe and Tyr
      variants caused a distorted folding conformation, especially at the E-ring site,
      which generated the aberrantly cyclized products germanicol and lupeol. The L734G
      and L734A variants exhibited significantly decreased activities but yielded
      taraxerol in a high production ratio. The Val, Ile, and Met variants showed
      markedly high activities (56-78 % of wild-type activity); therefore, appropriate
      steric bulk is required at this position. The aliphatic variants of Tyr736 showed
      markedly decreased activities, but the Phe mutant exhibited high activity (67 %),
      which indicates that the pi electrons are critical for catalysis. Homology
      modeling indicated that Tyr736 and Leu734 are perpendicular to the substrate and
      are situated face to face, which suggests that a CH-pi interaction occurs between
      Tyr736 and Leu734, reinforcing the protein architecture, and that Tyr736 cannot
      stabilize cationic intermediates through a cation-pi interaction.

PMID- 29214723
TI  - Longitudinal Analysis of Quality of Life, Clinical, Radiographic,
      Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous
      Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.
AB  - BACKGROUND: Changes in clinical variables associated with the administration of
      pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and
      cardiomegaly have not been described. OBJECTIVES: To investigate the effect of
      pimobendan on clinical variables and the relationship between a change in heart
      size and the time to congestive heart failure (CHF) or cardiac-related death
      (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated
      dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred
      and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS:
      Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4
      0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both
      groups were measured and compared at different time points (day 35 and onset of
      CHF) and over the study duration. Relationships between short-term changes in
      echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day
      35, heart size had reduced in the pimobendan group: median change in (Delta)
      LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to
      +0.03), P < 0.0001. Reduction in heart size was associated with increased time to
      CHF or CRD. Hazard ratio for a 0.1 increase in DeltaLVIDDN was 1.26, P = 0.0003.
      Hazard ratio for a 0.1 increase in DeltaLA:Ao was 1.14, P = 0.0002. At onset of
      CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan
      treatment reduces heart size. Reduced heart size is associated with improved
      outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable
      from those receiving placebo.

PMID- 29214726
TI  - Curb Your Embodiment.
AB  - To explain how abstract concepts are grounded in sensory-motor experiences,
      several theories have been proposed. I will discuss two of these proposals,
      Conceptual Metaphor Theory and Situated Cognition, and argue why they do not
      fully explain grounding. A central idea in Conceptual Metaphor Theory is that
      image schemas ground abstract concepts in concrete experiences. Image schemas
      might themselves be abstractions, however, and therefore do not solve the
      grounding problem. Moreover, image schemas are too simple to explain the full
      richness of abstract concepts. Situated cognition might provide such richness.
      Research in our laboratory, however, has shown that even for concrete concepts,
      sensory-motor grounding is task dependent. Therefore, it is questionable whether
      abstract concepts can be significantly grounded in sensory-motor processing.

PMID- 29214727
TI  - Importance and regulation of adult stem cell migration.
AB  - Cell migration is an essential process throughout the life of vertebrates,
      beginning during embryonic development and continuing throughout adulthood. Stem
      cells have an inherent ability to migrate, that is as important as their capacity
      for self-renewal and differentiation, enabling them to maintain tissue
      homoeostasis and mediate repair and regeneration. Adult stem cells reside in
      specific tissue niches, where they remain in a quiescent state until called upon
      and activated by tissue environmental signals. Cell migration is a highly
      regulated process that involves the integration of intrinsic signals from the
      niche and extrinsic factors. Studies using three-dimensional in vitro models have
      revealed the astonishing plasticity of cells in terms of the migration modes
      employed in response to changes in the microenvironment. These same properties
      can, however, be subverted during the development of some pathologies such as
      cancer. In this review, we describe the response of adult stem cells to migratory
      stimuli and the mechanisms by which they sense and transduce intracellular
      signals involved in migratory processes. Understanding the molecular events
      underlying migration may help develop therapeutic strategies for regenerative
      medicine and to treat diseases with a cell migration component.

PMID- 29214729
TI  - Finasteride inhibited brain dopaminergic system and open-field behaviors in
      adolescent male rats.
AB  - AIMS: Finasteride inhibits the conversion of testosterone to dihydrotestosterone.
      Because androgen regulates dopaminergic system in the brain, it could be
      hypothesized that finasteride may inhibit dopaminergic system. The present study
      therefore investigates the effects of finasteride in adolescent and early
      developmental rats on dopaminergic system, including contents of dopamine and its
      metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine
      hydroxylase expressions both at gene and protein levels. Meanwhile, open-field
      behaviors of the rats are examined because of the regulatory effect of
      dopaminergic system on the behaviors. METHODS: Open-field behaviors were
      evaluated by exploratory and motor behaviors. Dopamine and its metabolites were
      assayed by liquid chromatography-mass spectrometry. Tyrosine hydroxylase mRNA and
      protein expressions were determined by real-time qRT-PCR and western blot,
      respectively. RESULTS: It was found that in adolescent male rats, administration
      of finasteride at doses of 25 and 50 mg/kg for 14 days dose dependently inhibited
      open-field behaviors, reduced contents of dopamine and its metabolites in frontal
      cortex, hippocampus, caudate putamen, nucleus accumbens, and down-regulated
      tyrosine hydroxylase mRNA and protein expressions in substantia nigra and ventral
      tegmental area. However, there was no significant change of these parameters in
      early developmental rats after finasteride treatment. CONCLUSION: These results
      suggest that finasteride inhibits dopaminergic system and open-field behaviors in
      adolescent male rats by inhibiting the conversion of testosterone to
      dihydrotestosterone, and imply finasteride as a potential therapeutic option for
      neuropsychiatric disorders associated with hyperactivities of dopaminergic system
      and androgen.

PMID- 29214728
TI  - Disruption of network for visual perception of natural motion in primary
      dystonia.
AB  - In healthy subjects, brain activation in motor regions is greater during the
      visual perception of "natural" target motion, which complies with the two-thirds
      power law, than of "unnatural" motion, which does not. It is unknown whether
      motion perception is normally mediated by a specific network that can be altered
      in the setting of disease. We used block-design functional magnetic resonance
      imaging and covariance analysis to identify normal network topographies activated
      in response to "natural" versus "unnatural" motion. A visual motion perception
      related pattern (VPRP) was identified in 12 healthy subjects, characterized by
      covarying activation responses in the inferior parietal lobule, frontal
      operculum, lateral occipitotemporal cortex, amygdala, and cerebellum (Crus I).
      Selective VPRP activation during "natural" motion was confirmed in 12 testing
      scans from healthy subjects. Consistent network activation was not seen, however,
      in 29 patients with dystonia, a neurodevelopmental disorder in which motion
      perception pathways may be involved. Using diffusion tractography, we evaluated
      the integrity of anatomical connections between the major VPRP nodes. Indeed,
      fiber counts in these pathways were substantially reduced in the dystonia
      subjects. In aggregate, the findings associate normal motion perception with a
      discrete brain network which can be disrupted under pathological conditions.

PMID- 29214730
TI  - Conceptual and Operational Definitions for the Nursing Diagnosis "Urinary
      Retention".
AB  - PURPOSE: To develop conceptual and operational definitions for defining
      characteristics and related factors for nursing diagnosis of urinary retention,
      as contained in Taxonomy II of NANDA-I. DATA SOURCES: Integrative literature
      review and elaboration of terms related to urinary retention. DATA SYNTHESIS: It
      includes operational and conceptual definitions of the nursing diagnosis urinary
      retention. CONCLUSIONS: It is necessary to review the definition of this nursing
      diagnosis and most of its defining characteristics and related factors.
      IMPLICATIONS FOR NURSING PRACTICE: The use of internationally known terms for
      various disciplines in areas of common knowledge helps to standardize the
      language used by professionals.

PMID- 29214731
TI  - Perception of Human Interaction Based on Motion Trajectories: From Aerial Videos
      to Decontextualized Animations.
AB  - People are adept at perceiving interactions from movements of simple shapes, but
      the underlying mechanism remains unknown. Previous studies have often used object
      movements defined by experimenters. The present study used aerial videos recorded
      by drones in a real-life environment to generate decontextualized motion stimuli.
      Motion trajectories of displayed elements were the only visual input. We measured
      human judgments of interactiveness between two moving elements and the dynamic
      change in such judgments over time. A hierarchical model was developed to account
      for human performance in this task. The model represents interactivity using
      latent variables and learns the distribution of critical movement features that
      signal potential interactivity. The model provides a good fit to human judgments
      and can also be generalized to the original Heider-Simmel animations (1944). The
      model can also synthesize decontextualized animations with a controlled degree of
      interactiveness, providing a viable tool for studying animacy and social
      perception.

PMID- 29214732
TI  - Commentary on "Methodological recommendations for cognition trials in bipolar
      disorder by the International Society for Bipolar Disorders Targeting Cognition
      Task Force".

PMID- 29214733
TI  - Timing and sequence of emergence of permanent teeth in Syrian schoolchildren.
AB  - AIM: The aim of the present study was to investigate the timing and sequence of
      the eruption of permanent teeth in Syrian schoolchildren. METHODS: A total of
      1211 children aged 5-13 years were included. Every permanent tooth was scored
      according to its clinical stage of eruption. The significance of difference was
      tested using t test. RESULTS: The mean number of erupted teeth in children aged 5
      6 years was 2.41 +/- 2.68, and reached to 24.48 +/- 3.60 in those ages between 12
      and 13 years. Mandibular teeth erupted earlier than maxillary opposing teeth in
      both sexes, except upper premolars. The eruption significantly proceeded in girls
      when compared to boys. Differences were significant for numbers 11 (P = .003), 21
      (P = .035), 13 (P = .013), 42 (P = .038), 33 (P = .009), and 45 (P = .012). There
      was no significant difference between contralateral teeth (right and left) in the
      mean age of eruption in both arches. Lower central incisors and first molars were
      the earliest teeth to emerge in both sexes. Second molars were the last teeth to
      emerge in boys (maxilla: 11.68 years, mandible: 11.15 years) and girls (maxilla:
      11.2 years, mandible 10.99 years). CONCLUSION: Findings could be used as Syrian
      standards of eruption when health professionals assess normal occlusion and need
      to determine the correct timing for preventive or corrective procedures.

PMID- 29214734
TI  - Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End
      Stage Renal Disease Patients Undergoing Hemodialysis.
AB  - Prevalence of cognitive function decline in end stage renal disease (ESRD)
      patients undergoing hemodialysis is higher than in the general population. We
      analyzed risk factors for cognitive function decline in those patients. This
      study included 93 ESRD patients undergoing hemodialysis two or three times a week
      in three centers for hemodialysis in Montenegro. The cognitive status of patients
      was assessed using the mini mental score examination (MMSE) test. All 93 patients
      have been divided into three groups according to the results of MMSE. Patients in
      the first group had severe cognitive impairment and MMSE score below 17 (26.88%),
      patients in the second group with MMSE score 18-23 had moderate cognitive
      impairment (40.86%) and third group of patients have MMSE >24 and no cognitive
      impairment (32.26%). There were no significant differences between groups for
      gender, smoking habits and level of parathyroid hormone. Level of schooling was
      significantly different between groups of patients (P < 0.001). Laboratory
      markers observed in this study with significant differences between groups were:
      IGF 1, IGFBP 3, erythrocytes and hemoglobin (P < 0.001, P = 0.004, P < 0.001, P =
      0.002, respectively). IGF 1 proved to be of great importance for evaluating
      cognitive status in our study. This marker was statistically different between
      groups (P < 0.001) and Tukey post hoc analysis showed significant differences
      between all three groups (first and second group P = 0.045, second and third
      group P = 0.015, first and third group P < 0.001). Our data suggest that IGF 1
      can be considered as novel biomarker for assessment of cognitive functioning in
      CKD patients, which can be of huge clinical importance.

PMID- 29214735
TI  - The mechanism study of miR-125b in occurrence and progression of multiple
      myeloma.
AB  - Although many efforts have contributed to improve our knowledge of molecular
      pathogenesis about multiple myeloma (MM), the role and significance of microRNAs
      and long noncoding RNAs in MM cells, along with the core mechanism remains
      virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were
      detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the
      Notch-1 pathway-related proteins were assessed by MTT method and western blot,
      respectively. We also investigated the regulation effect between MALAT1 and
      Notch1 pathway. Moreover, the connection between Notch1 signaling and MM cell
      growth was discussed in-depth. The reverse effect of pcDNA-Notch1 on the cell
      viability and Notch-1 pathway proteins induced by Si-MALAT1 was also studied.
      Furthermore, miR-125b overexpressing MM cell lines were injected subcutaneously
      into nude mice. MiR-125b and MALAT1 were inversely expressed in MM cell lines.
      Lenti-Sh-miR-125b inhibited the expression of MALAT1 and Notch-1 protein. Binding
      sites were confirmed between miR-125b and MALAT1, and silencing MALAT1 did not
      alter the expression of Notch-1. The apoptosis rate was increased and the
      survival rate was decreased obviously in GSI XII (targeted cleavage of Notch-1
      receptor) group, along with the inhibited Notch1 and HES1 proteins. Moreover, the
      decreased cell viability and Notch-1 pathway proteins induced by Si-MALAT1 could
      be reversed by pcDNA-Notch1. Lenti-Sh-miR-125b promoted survival and decreased
      Notch1 and HES1 proteins levels, while this effect was reversed by si -MALAT1.
      MiR-125b regulated MALAT1 expression via Notch1 signaling pathway to regulate
      cell growth, thus participating in the occurrence and progression of MM, which
      functioned as a therapeutic target for tracking MM.

PMID- 29214736
TI  - Definite stent thrombosis after drug-eluting stent implantation in coronary
      bifurcation lesions: A meta-analysis of 3,107 patients from 14 randomized trials.
AB  - BACKGROUND: Bifurcation percutaneous coronary intervention (PCI) is a challenging
      procedure, but there are currently inadequate data about definite stent
      thrombosis (ST) rates of single-stent versus double-stent strategies (SS and DS,
      respectively). METHODS AND RESULTS: Randomized clinical trials (RCTs) comparing
      SS and DS strategies were searched through PubMed, Embase, and the Cochrane
      Central Register of Controlled Trials. Fourteen RCTs involving 3,107 patients
      were analyzed. Owing to the high crossover rate (16.49%), both intention-to-treat
      (ITT) and as-treated (AT) analyses were performed. In the ITT population, there
      was a significantly lower rate of early definite ST in the SS group (0.26%; DS
      group 1.14%; P = 0.021). Similarly, in the AT population, there was a
      significantly lower rate of early definite ST in the SS group (0.23%, DS group
      1.07%; P = 0.042). True bifurcation subgroup analysis also showed a significantly
      lower early definite ST in the SS group (OR = 0.36, 95% CI = 0.15-0.86, P =
      0.042) in the ITT population. There was no significant difference of overall,
      acute, subacute, and late definite ST between the 2 groups. CONCLUSIONS: Early
      definite ST is reduced when a SS strategy is used in bifurcation lesions.

PMID- 29214738
TI  - Successful treatment of pyoderma gangrenosum with anakinra in a patient with
      Wiskott-Aldrich syndrome.

PMID- 29214737
TI  - Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A
      protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and
      HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).
AB  - OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose
      combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1
      and hepatitis C virus (HCV) have mainly included treatment-naive patients without
      cirrhosis. We aimed to evaluate the efficacy and safety of this combination in
      treatment-experienced patients with and without cirrhosis. METHODS: We conducted
      a multicentre, open-label, double-arm, nonrandomized study in patients coinfected
      with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral
      suppression on their antiretroviral regimens. All patients were pretreated with a
      first-generation NS3/4A protease inhibitor (PI) plus pegylated
      interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for
      12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a
      sustained virological response (SVR) 12 weeks after the end of therapy. Secondary
      endpoints included safety, pharmacokinetics and patient-reported outcomes.
      RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients
      [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR,
      with similar rates of SVR in those with and without cirrhosis. Tolerance was
      satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported
      outcomes, only fatigue significantly decreased at the end of treatment compared
      with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean
      tenofovir area under the plasma concentration-time curve (AUC) at week 4 was
      high, with mean +/- SD AUC variation between baseline and week 4 higher in
      cirrhotic than in noncirrhotic patients (3261.57 +/- 1920.47 ng/mL vs. 1576.15 +/
      911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%),
      hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia
      (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS:
      LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV
      genotype 1 and HIV-1, including patients with cirrhosis.

PMID- 29214739
TI  - Evaluation of Intradialytic Hypertension Using Bioelectrical Impedance Combined
      With Echocardiography in Maintenance Hemodialysis Patients.
AB  - Although intra-dialytic hypertension (IDH) has been noted in clinical settings
      for many years, its pathogenesis remains unclear. In this cross-sectional study,
      we analyzed IDH incidence in our center and the correlation between postdialysis
      volume state and IDH. One hundred thirty-one maintenance hemodialysis (MHD)
      patients were enrolled in our study, and bioelectrical impedance (BIA) and
      echocardiography (ECG) were recorded. In addition, demographic data were
      collected, and laboratory examinations were conducted. The patients were grouped
      into four groups according to the change in systolic blood pressure (SBP) between
      predialysis and postdialysis. The incidence of IDH was 10.7%. The proportion of
      extracellular water to total body weight (ECW/TW), as evaluated by BIA, was
      significantly higher in the IDH group than in the other three groups both in pre
      and post-dialysis. In particular, postdialysis SBP was highest in the highest
      tertile interval of ECW/TW. In addition, among the four groups, left ventricular
      volume (LVV) was highest in the IDH group. Binary logistic analyses revealed that
      predialysis SBP, postdialysis ECW/TW and LVV were independent risk factors of
      intradialytic hypertension. When predicting IDH, the AUC of the ROC curve was
      higher for ECW/TW combined with LVV (0.752, 95% CI 0.613-0.896) than for either
      LVV or ECW/TW alone. Our study further showed that post-dialysis volume expansion
      is an important factor for the development of IDH.

PMID- 29214740
TI  - A prospective multicentre randomized placebo-controlled superiority trial in
      patients with suspected bacterial endophthalmitis after cataract surgery on the
      adjuvant use of intravitreal dexamethasone to intravitreal antibiotics.
AB  - PURPOSE: We aimed to determine whether intravitreal dexamethasone as an adjuvant
      to intravitreal antibiotics is beneficial in the treatment of suspected bacterial
      endophthalmitis after cataract surgery. METHODS: Randomized, placebo-controlled
      superiority trial in three tertiary referral centres in the Netherlands. Patients
      with suspected bacterial endophthalmitis within 6 weeks after cataract surgery
      were eligible. A diagnostic vitreous biopsy was taken for culture, and patients
      received intravitreal injections of 400 MUg dexamethasone (without preservatives)
      or placebo, in addition to 0.2 mg vancomycin and 0.05 mg gentamicin. The
      vancomycin and dexamethasone or placebo injections were repeated once at day 3 or
      4. Primary outcome measure was best-corrected visual acuity (BCVA) at 1 year.
      RESULTS: Between 1 November 2004 and 1 March 2014 (excluding two interruptions
      totalling 20 months), 324 eligible patients presented. A total of 167 patients
      (81 dexamethasone, 86 placebo) were available for the intention-to-treat
      analysis. Biopsies of 114 patients (68%) were culture-positive. Final BCVA did
      not differ between the dexamethasone and the placebo group (logMAR 0.31 +/- 0.58
      versus 0.27 +/- 0.50; p = 0.90), nor did the number of patients with final vision
      of no light perception (LP, 7 versus 13). Pain, corneal oedema, the absence of a
      red fundus reflex on presentation, LP on presentation and culture of virulent
      pathogens from biopsy were statistically significantly associated with an
      unfavourable visual outcome. CONCLUSION: Intravitreal dexamethasone without
      preservatives as an adjuvant to intravitreal antibiotics does not improve visual
      acuity (VA) in patients treated for suspected bacterial endophthalmitis after
      cataract surgery.

PMID- 29214741
TI  - Laccase-Catalyzed Synthesis of Low-Molecular-Weight Lignin-Like Oligomers and
      their Application as UV-Blocking Materials.
AB  - The laccase-catalyzed oxidative polymerization of monomeric and dimeric lignin
      model compounds was carried out with oxygen as the oxidant in aqueous medium. The
      oligomers were characterized by using gel permeation chromatography (GPC) and
      matrix-assisted laser desorption ionization time-of-flight mass spectroscopy
      (MALDI-TOF MS) analysis. Oxidative polymerization led to the formation of
      oligomeric species with a number-average molecular weight (Mn ) that ranged from
      700 to 2300 Da with a low polydispersity index. Spectroscopic analysis provided
      insight into the possible modes of linkages present in the oligomers, and the
      oligomerization is likely to proceed through the formation of C-C linkages
      between phenolic aromatic rings. The oligomers were found to show good UV light
      absorption characteristics with high molar extinction coefficient (5000-38 000 m
      1  cm-1 ) in the UV spectral region. The oligomers were blended independently
      with polyvinyl chloride (PVC) by using solution blending to evaluate the
      compatibility and UV protection ability of the oligomers. The UV/Vis
      transmittance spectra of the oligomer-embedded PVC films indicated that these
      lignin-like oligomers possessed a notable ability to block UV light. In
      particular, oligomers obtained from vanillyl alcohol and the dimeric lignin model
      were found to show good photostability in accelerated UV weathering experiments.
      The UV-blocking characteristics and photostability were finally compared with the
      commercial low-molecular-weight UV stabilizer 2,4-dihydroxybenzophenone.

PMID- 29214742
TI  - Evaluation of efficacy and safety of dexamethasone intravitreal implants before
      and after vitrectomy in a real-life study.

PMID- 29214743
TI  - GC-MS/MS detects potential pregabalin abuse in susceptible subjects' hair.
AB  - Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage
      dependent calcium channels. It is recognised as efficacious in pathologies such
      as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin
      prescriptions have increased worldwide, reports of its abuse have been
      accumulating, mainly in patients with opioid abuse disorders. The present study
      investigated potential pregabalin abuse by means of hair analysis, a matrix that
      provides valuable retrospective information. Half of the pool of 280 susceptible
      patients had been occasional drug users and were being monitored for driving
      licence renewals. The other 140 patients had a history of opiate dependency and
      were monitored to assess compliance with methadone therapy. In view of
      determining pregabalin in hair samples, it was extracted in methanol,
      successfully derivatised to give the ethyl chloroformate derivative, and finally
      pregabalin was analysed by gas chromatography-tandem mass spectrometry.
      Selectivity, linearity, limit of detection, limit of quantification, recovery,
      intra- and inter-day precision, and accuracy of the quantification procedure were
      appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50
      pg/mg, respectively. We found 10.7% of hair samples from methadone patients and
      4.29% from occasional drug users were positive to pregabalin without medical
      prescription. The mean pregabalin concentration in hair was higher than in
      consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results
      suggest that pregabalin possesses a significant abuse potential particularly
      among individuals attending opiate dependence services and that pregabalin abuse
      is a serious emerging issue, which should be carefully monitored.

PMID- 29214744
TI  - Exposure to cadmium during gestation and lactation affects development and
      function of Leydig cells in male offspring.
AB  - Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male
      offspring arises much concern recently, but its toxic effects on the development
      of Leydig cells and androgen synthesis have not been elucidated. In this study,
      female rats were exposed to Cd during gestation and lactation, and the
      development of Leydig cells in the first filial-generation (F1) male rats was
      investigated. The steroidogenic signaling pathway and biomarkers related to the
      development of Leydig cells were detected to disclose how maternal Cd-exposure
      caused reproductive damage. F1 male rats with maternal Cd-exposure gained a low
      relative weight of testis and declined levels of steroid hormones. Maternal Cd
      exposure interrupted the development of Leydig cells with high expression of
      SRD5alpha and cell morphology of immature Leydig cells in adulthood, inhibited
      the activation of cyclic adenosine monophosphate/ protein kinase A signaling
      pathway and down-regulated the steroidogenic enzymes. These results would help to
      disclose the origin of male sexual dysfunction in the developmental stages of
      Leydig cells.

PMID- 29214746
TI  - Case of idiopathic and complete appendiceal intussusception.
AB  - Appendiceal intussusception is a rare disease in which the appendix invaginates
      into the cecum. It is often caused by organic diseases. The present case involved
      an appendiceal intussusception without an organic disease, and laparoscopic
      resection of part of the cecum was performed. Appendiceal intussusception has
      various causes, including malignant diseases. Therefore, diagnosis and selection
      of operative method are complex and could potentially lead to an excessively
      invasive option. By performing SILS with a multiuse single-site port, we were
      able to provide an appropriate, non-invasive treatment that had a good esthetic
      outcome.

PMID- 29214747
TI  - Prognostic effect of body mass index to mortality in Korean older persons.
AB  - AIM: Body mass index (BMI) is regarded as a predictor of life expectancy and a
      determinant of mortality. However, the effect of age on BMI-related mortality
      remains unclear. The aim of the present study was to examine the prognostic
      effect of BMI to mortality risk among Korean older persons. METHODS: Data were
      collected from the Korean National Health Insurance Services' Senior Cohort
      database. This study analyzed the data of 79 341 men and 91 298 women aged >=65
      years who underwent health examinations in the 2007 fiscal year. Individual
      mortality was identified 5 years after 2008. The participants were stratified
      into seven groups according to basal BMI. Hazard ratios of death were calculated
      through Cox proportional hazards model after adjusting for age, sex, smoking
      status, exercise, alcohol intake and income. RESULTS: During the 5-year follow
      up, 11 651 men and 7 235 women died. In both sexes, a lower BMI had a higher
      hazard ratio (HR), but the trend of increasing HR at high BMI was not clear. For
      men, the lowest HR was 0.79 (95% CI 0.71-0.87) at a BMI of 27.5-30.0 kg/m2 . For
      women, the lowest HR was 0.84 (95% CI 0.78-0.91) at a BMI of 25.0-27.5 kg/m2 .
      For both sexes, the relative mortality risk was associated with a lower BMI.
      CONCLUSIONS: A high BMI is not associated with increased mortality in older
      adults aged >=65 years, whereas a lower BMI is associated with an increased
      mortality risk in later life in this population. Geriatr Gerontol Int 2018; 18:
      538-546.

PMID- 29214750
TI  - Comparison of prothrombin time INR and clot waveform analysis performed with 129
      mmol/L and 105-mmol/L citrate tubes.

PMID- 29214748
TI  - Alterations in the in vitro and in vivo regulation of muscle regeneration in
      healthy ageing and the influence of sarcopenia.
AB  - BACKGROUND: Sarcopenia is defined as the age-related loss of skeletal muscle mass
      and function. While all humans lose muscle with age, 2-5% of elderly adults
      develop functional consequences (disabilities). The aim of this study was to
      investigate muscle myogenesis in healthy elderly adults, with or without
      sarcopenia, compared with middle-aged controls using both in vivo and in vitro
      approaches to explore potential biomarker or causative molecular pathways
      associated with sarcopenic versus non-sarcopenic skeletal muscle phenotypes
      during ageing. METHODS: Biomarkers of multiple molecular pathways associated with
      muscle regeneration were analysed using quantitative polymerase chain reaction in
      quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7)
      or non-sarcopenic (HENS, n = 21) and healthy middle-aged control (HMC, n = 22)
      groups. An in vitro system of myogenesis (using myoblasts from human donors aged
      17-83 years) was used to mimic the environmental challenges of muscle
      regeneration over time. RESULTS: The muscle biopsies showed evidence of satellite
      cell activation in HENS (Pax3, P < 0.01, Pax7, P < 0.0001) compared with HMC.
      Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5
      (Myf5) (P < 0.0001) and the late myogenesis marker myogenin (MyoG) (P < 0.01)
      were increased in HENS. In addition, there was a 30-fold upregulation of TNF
      alpha in HENS compared with HMC (P < 0.0001). The in vitro system demonstrated
      age-related upregulation of pro-inflammatory cytokines (2-fold upregulation of
      interleukin (IL)-6, IL-8 mRNA, increased secretion of tumor necrosis factor-alpha
      (TNF-alpha) and IL-6, all P < 0.05) associated with impaired kinetics of myotube
      differentiation. The HSE biopsy samples showed satellite cell activation (Pax7, P
      < 0.05) compared with HMC. However, no significant upregulation of the early
      myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker
      myogenin was upregulated (P < 0.05). Higher activation of the oxidative stress
      pathway was found in HENS compared with the HSE group. In contrast, there was 10
      fold higher upregulation of HSPA1A a stress-induced chaperone acting upon
      misfolded proteins in HSE compared with the HENS group. CONCLUSIONS: Both
      pathological and adaptive processes are active in skeletal muscle during healthy
      ageing. Muscle regeneration pathways are activated during healthy ageing, but
      there is evidence of dysregulation in sarcopenia. In addition, increased cellular
      stress, with an impaired oxidative-stress and mis-folded protein response
      (HSPA1A), may be associated with the development of sarcopenia. The in vitro
      system of young and old myoblasts replicated some of the differences between
      young and old muscle.

PMID- 29214751
TI  - Multi-center Performance Evaluations of Tacrolimus and Cyclosporine
      Electrochemiluminescence Immunoassays in the Asia-Pacific Region.
AB  - BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are
      vital for solid organ transplant patients to prevent rejection. However, toxicity
      is a concern, and absorption is highly variable across patients; therefore, ISD
      levels need to be precisely monitored. In the Asia-Pacific (APAC) region,
      tacrolimus and cyclosporine concentrations are typically measured using
      immunoassays. The objective of this study was to assess the analytical
      performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence
      immunoassays (ECLIAs). METHODS: This evaluation was performed in seven centers
      across China, South Korea, and Malaysia. Imprecision (repeatability and
      reproducibility), assay accuracy, and lot-to-lot reagent variability were tested.
      The Elecsys ECLIAs were compared with commercially available immunoassays
      (Architect, Dimension, and Viva-E systems) using whole blood samples from
      patients with various transplant types (kidney, liver, heart, and bone marrow).
      RESULTS: Coefficients of variation for repeatability and reproducibility were
      <=5.4% and <=12.4%, respectively, for the tacrolimus ECLIA, and <=5.1% and
      <=7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the
      tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope
      values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even
      closer agreements with the Architect, Dimension, and Viva-E systems (slope values
      of 1.04, 1.04, and 1.09, respectively). No major differences were observed among
      the different transplant types. CONCLUSIONS: The tacrolimus and cyclosporine
      ECLIAs demonstrated excellent precision and close agreement with other
      immunoassays tested. These results show that both assays are suitable for ISD
      monitoring in an APAC population across a range of different transplant types.

PMID- 29214752
TI  - Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management
      of Pre-eclampsia: Experience in a Specialized Perinatal Care Center.
AB  - BACKGROUND: Management of pregnant women at high risk of pre-eclampsia (PE)
      requires frequent monitoring, with referral to specialized perinatal care
      centers. Reliable tests are necessary to improve prediction of PE and related
      complications and to assess disease severity and progression. An imbalance in two
      biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth
      factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is
      increased in pregnant women before the onset of PE. An elevated ratio is highly
      predictive of PE, whereas the diagnosis of PE can be ruled out within one week
      for low ratios. The main objective of this study was to assess whether a low sFlt
      1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one
      week. METHODS: We performed a prospective, monocentric, observational study to
      evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for
      predicting -PE in a group of 67 high-risk pregnant women (20-37 gestation weeks).
      RESULTS: Among the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than
      38; none developed subsequent PE leading to a negative predictive value of 100%.
      Eight patients developed clinical PE. The positive predictive value was 21% at
      one week and 18% at four weeks, in accordance with previous studies. CONCLUSIONS:
      The serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out
      PE. Using these biomarkers in routine management of PE may improve clinical care
      and avoid inappropriate hospitalization, which has a significant economic impact.

PMID- 29214753
TI  - Increasing Incidence of Listeriosis and Infection-associated Clinical Outcomes.
AB  - BACKGROUND: Listeriosis caused by Listeria monocytogenes has a high case-fatality
      rate (CFR) of approximately 20% to 30%. An increasing incidence of listeriosis
      has been reported in many countries recently. We investigated the annual
      incidence, clinical characteristics, and outcomes of listeriosis at three
      different hospitals in Korea and evaluated the effects of appropriate empiric
      antimicrobial treatments on patient outcomes. METHODS: We retrospectively
      collected the data of all culture-positive cases of human listeriosis from three
      hospitals of different sizes in Korea during 2006-2016 and calculated the annual
      number of cases and incidence per 100,000 admissions. RESULTS: A total of 58
      patients with L. monocytogenes were included in this study. The incidence of
      listeriosis was significantly higher in 2013-2016 than in 2006-2012 (RR 3.1; 95%
      CI 1.79-5.36; P<0.001), mainly because of an increase in patients over 60 years
      of age (RR 3.69; 95% CI 1.70-8.02; P<0.001). Multivariate analysis showed that
      healthcare-associated infection (adjusted OR, 12.15; 95% CI, 2.56-86.01; P=0.004)
      and empirical treatment with first-line antimicrobial agents (adjusted OR, 0.08;
      95% CI, 0.00-0.63; P=0.044) were associated with CFR. CONCLUSIONS: Healthcare
      associated infections caused by L. monocytogenes are associated with high CFR.
      Adequate initial empirical treatments could reduce CFR, suggesting that careful
      consideration of an empirical antimicrobial regimen is warranted for elderly or
      immunocompromised patients admitted to the hospital.

PMID- 29214754
TI  - Utility of Conventional Culture and MALDI-TOF MS for Identification of Microbial
      Communities in Bronchoalveolar Lavage Fluid in Comparison with the GS Junior Next
      Generation Sequencing System.
AB  - BACKGROUND: Diverse microbiota exist in the lower respiratory tract. Although
      next generation sequencing (NGS) is the most widely used microbiome analysis
      technique, it is difficult to implement NGS in clinical microbiology
      laboratories. Therefore, we evaluated the performance of conventional culture
      methods together with matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF MS) in identifying microbiota in bronchoalveolar
      lavage (BAL) fluid. METHODS: BAL fluid samples (n=27) were obtained from patients
      undergoing diagnostic bronchoscopy for lung mass evaluation. Bacterial and fungal
      culture was performed with conventional media used in clinical microbiology
      laboratories. On an average, 20 isolated colonies were picked from each agar
      plate and identified by MALDI-TOF MS. Microbiome analysis using 16S rRNA NGS was
      conducted for comparison. RESULTS: Streptococcus spp. and Neisseria spp. were
      most frequently cultured from the BAL fluid samples. In two samples,
      Enterobacteriaceae grew predominantly on MacConkey agar. Actinomyces and
      Veillonella spp. were commonly identified anaerobes; gut bacteria, such as
      Lactobacillus, Bifidobacterium, and Clostridium, and fungi were also isolated.
      NGS revealed more diverse bacterial communities than culture, and Prevotella spp.
      were mainly identified solely by NGS. Some bacteria, such as Staphylococcus spp.,
      Clostridium spp., and Bifidobacterium spp., were identified solely by culture,
      indicating that culture may be more sensitive for detecting certain bacteria.
      CONCLUSIONS: Culture and NGS of BAL fluid samples revealed common bacteria with
      some different microbial communities. Despite some limitations, culture combined
      with MALDI-TOF MS might play a complementary role in microbiome analysis using
      16S rRNA NGS.

PMID- 29214755
TI  - Comparative Evaluation of the Loop-Mediated Isothermal Amplification Assay for
      Detecting Pulmonary Tuberculosis.
AB  - BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor
      settings because of limited accessibility to molecular diagnostics. The aim of
      this study was to evaluate the performance of the loop-mediated isothermal
      amplification kit (TB-LAMP) for TB diagnosis compared with conventional and
      molecular tests. METHODS: A total of 290 consecutive sputum samples were
      collected from May till September, 2015. All samples were processed using the N
      Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and
      liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP
      for smear-positive and smear-negative samples with culture positivity was 92.0%
      and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative
      samples; however, all those samples were also positive by real-time PCR. In
      addition, none of the samples positive for nontuberculous mycobacteria by culture
      were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR
      was good; however, the concordance rate was significantly lower for real-time PCR
      positive samples with Ct values of 30-35. CONCLUSIONS: TB-LAMP could replace
      smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not
      feasible because of poor infrastructure.

PMID- 29214756
TI  - Serum Cytokine Profile in Patients with Chronic Rhinosinusitis with Nasal
      Polyposis Infected by Aspergillus flavus.
AB  - BACKGROUND: Fungi, especially Aspergillus flavus, can cause chronic
      rhinosinusitis with nasal polyposis and modulate host innate immune components.
      The objective of this study was to examine the serum levels of T helper (Th) cell
      subset Th1, Th2, and Th17 cytokines and total IgE in patients having chronic
      rhinosinusitis with nasal polyposis and Aspergillus flavus infection. METHODS: A
      case-control study including 40 patients with chronic rhinosinusitis with nasal
      polyposis and 20 healthy controls was conducted. Aspergillus flavus infection was
      confirmed by standard potassium hydroxide (KOH) testing, culture, and PCR. Serum
      samples of all patients and controls were analyzed for various cytokines
      (interleukins [IL]-1beta, IL-2, IL-4, IL-6, IL-17, IL-21, IL-27, TGF-beta) and
      total IgE by ELISA. Data from patients with Aspergillus flavus infection and
      healthy volunteers were compared using the independent t-test and non-parametric
      Mann-Whitney U test. RESULTS: Aspergillus flavus infection was found in 31
      (77.5%) patients with chronic rhinosinusitis with nasal polyposis. IL-1beta, IL
      17, IL-21, and TGF-beta serum levels were significantly higher in these patients
      than in controls; however, IL-2, IL-4, IL-6, and IL-27 levels were lower.
      Compared with nine (22.5%) patients without Aspergillus flavus infection, IL-17
      level was higher while IL-2 level was lower in patients with Aspergillus flavus
      infection. Total IgE was significantly higher in patients with Aspergillus flavus
      infection than in controls. CONCLUSIONS: High levels of IL-17 and its regulatory
      cytokines in patients with chronic rhinosinusitis with nasal polyposis infected
      by Aspergillus flavus raise a concern about effective disease management and
      therapeutic recovery. Surgical removal of the nasal polyp being the chief
      management option, the choice of post-operative drugs may differ in eosinophilic
      vs. non-eosinophilic nasal polyposis. The prognosis is likely poor, warranting
      extended care.

PMID- 29214757
TI  - Clinical and Cytogenetic Profiles of Rhabdomyosarcoma with Bone Marrow
      Involvement in Korean Children: A 15-Year Single-Institution Experience.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in
      children. Alveolar RMS (ARMS) is characterized by FOXO1-related chromosomal
      translocations that result in a poorer clinical outcome compared with embryonal
      RMS (ERMS). Because the chromosomal features of RMS have not been comprehensively
      defined, we analyzed the clinical and laboratory data of childhood RMS patients
      and determined the clinical significance of chromosomal abnormalities in the bone
      marrow. METHODS: Fifty-one Korean patients with RMS <18 years of age treated
      between 2001 and 2015 were enrolled in this study. Clinical factors, bone marrow
      and cytogenetic results, and overall survival (OS) were analyzed. RESULTS: In
      total, 36 patients (70.6%) had ERMS and 15 (29.4%) had ARMS; 80% of the ARMS
      patients had stage IV disease. The incidences of bone and bone marrow metastases
      were 21.6% and 19.6%, respectively, and these results were higher than previously
      reported results. Of the 40 patients who underwent bone marrow cytogenetic
      investigation, five patients had chromosomal abnormalities associated with the
      13q14 rearrangement. Patients with a chromosomal abnormality (15 vs 61 months,
      P=0.037) and bone marrow involvement (17 vs 61 months, P=0.033) had a
      significantly shorter median OS than those without such characteristics. Two
      novel rearrangements associated with the 13q14 locus were detected. One patient
      with concomitant MYCN amplification and PAX3/FOXO1 fusion showed an aggressive
      clinical course. CONCLUSIONS: A comprehensive approach involving conventional
      cytogenetics and FOXO1 FISH of the bone marrow is needed to assess high-risk ARMS
      patients and identify novel cytogenetic findings.

PMID- 29214758
TI  - Comparison of Four Human Papillomavirus Genotyping Methods: Next-generation
      Sequencing, INNO-LiPA, Electrochemical DNA Chip, and Nested-PCR.
AB  - BACKGROUND: Human papillomavirus (HPV) infection causes cervical cancer, thus
      necessitating early detection by screening. Rapid and accurate HPV genotyping is
      crucial both for the assessment of patients with HPV infection and for
      surveillance studies. METHODS: Fifty-eight cervicovaginal samples were tested for
      HPV genotypes using four methods in parallel: nested-PCR followed by conventional
      sequencing, INNO-LiPA, electrochemical DNA chip, and next-generation sequencing
      (NGS). RESULTS: Seven HPV genotypes (16, 18, 31, 33, 45, 56, and 58) were
      identified by all four methods. Nineteen HPV genotypes were detected by NGS, but
      not by nested-PCR, INNO-LiPA, or electrochemical DNA chip. CONCLUSIONS: Although
      NGS is relatively expensive and complex, it may serve as a sensitive HPV
      genotyping method. Because of its highly sensitive detection of multiple HPV
      genotypes, NGS may serve as an alternative for diagnostic HPV genotyping in
      certain situations.

PMID- 29214759
TI  - Clinical Implications of Quantitative JAK2 V617F Analysis using Droplet Digital
      PCR in Myeloproliferative Neoplasms.
AB  - BACKGROUND: JAK2 V617F is the most common mutation in myeloproliferative
      neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is
      useful for classifying patients with MPN into subgroups and for prognostic
      prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible
      quantitative analysis of DNA. This study was designed to verify the correlation
      of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate
      clinical implications of the mutational burden. METHODS: Peripheral blood or bone
      marrow samples were obtained from 56 patients newly diagnosed with MPN or
      previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment
      between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as
      a diagnostic work-up. The same samples were used for ddPCR to determine the
      correlation between assays and establish a detection sensitivity cut-off.
      Clinical and hematologic aspects were reviewed. RESULTS: Forty-two (75%) and 46
      (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR,
      respectively. The mean mutated allele frequency at diagnosis was 37.5+/-30.1% and
      was 40.7+/-31.2% with ddPCR, representing a strong correlation (r=0.9712,
      P<0.001). Follow-up samples were available for 12 patients, including eight that
      were JAK2 V617F-positive. Of these, mutational burden reduction after treatment
      was observed in six patients (75%), consistent with trends of hematologic
      improvement. CONCLUSIONS: Quantitative analysis of the JAK2 V617F mutation using
      ddPCR was highly correlated with pyrosequencing data and may reflect the clinical
      response to treatment.

PMID- 29214760
TI  - Prevalence of blaZ Gene and Performance of Phenotypic Tests to Detect
      Penicillinase in Staphylococcus aureus Isolates from Japan.
AB  - Guidelines recommend that clinical laboratories perform phenotypic tests
      (nitrocefin-based test and penicillin 10-U [P10] or 1-U [P1] zone edge tests) to
      detect penicillinase in Staphylococcus aureus isolates. This study aimed to
      assess the prevalence of blaZ encoding penicillinase and perform various
      phenotypic tests in S. aureus isolates from Japan. We prospectively collected 200
      methicillin-susceptible S. aureus isolates from June 2015 to January 2016 and
      performed six phenotypic tests (nitrocefin-based test, P10 zone edge test/P10
      diffusion test, penicillin 2-U [P2] zone edge test/P2 diffusion test, and
      cloverleaf test) on each sample. We confirmed the presence of blaZ (two blaZ
      positive isolates) using PCR. Using blaZ PCR as a standard, we observed a low
      sensitivity (50%) and positive predictive value (PPV, 50%) of the nitrocefin
      based test, low PPV (18.2%) of the P10 zone edge test, low sensitivity (50%) of
      the P10 diffusion test, low PPV (50% and 22.2%) of the P2 zone edge test and P2
      diffusion test, respectively, and low sensitivity (50%) of the cloverleaf test.
      These data suggest a low performance (sensitivity and PPV) of these six
      phenotypic tests because of the low prevalence (1%) of blaZ in S. aureus isolates
      from Japan.

PMID- 29214762
TI  - Incidental Identification of Plasmodium vivax During Routine Complete Blood Count
      Analysis Using the UniCel DxH 800.

PMID- 29214761
TI  - Clinicopathological Characteristics of Hyperdiploidy with High-Risk Cytogenetics
      in Multiple Myeloma.
AB  - In multiple myeloma (MM), hyperdiploidy (HD) is known to impart longer overall
      survival. However, it is unclear whether coexistent HD ameliorates the adverse
      effects of known high-risk cytogenetics in MM patients. To address this issue, we
      investigated the clinicopathological characteristics of HD with high-risk
      cytogenetics in MM. Ninety-seven patients with MM were included in the study. For
      metaphase cytogenetics (MC), unstimulated cells from bone marrow aspirates were
      cultured for either 24 or 48 hours. To detect HD by interphase fluorescence in
      situ hybridization (iFISH), we assessed trisomies of chromosomes 5, 7, 9, 11, 15,
      and 17. Of the 97 MM patients, 40 showed HD. The frequency of co-occurrence of HD
      and high-risk cytogenetics was 14% (14/97). When the clinicopathological
      characteristics were compared between the two groups of HD with high-risk
      cytogenetics vs. non-HD (NHD) with high-risk cytogenetics, the level of beta 2
      microglobulin and stage distribution significantly differed (P=0.020, P=0.032,
      respectively). This study shows that some of the clinicopathological
      characteristics of MM patients with high-risk cytogenetics differ according to HD
      or NHD status.

PMID- 29214763
TI  - A Novel e8a2BCR-ABL1 Fusion Transcript without Insertion Sequence in a Patient
      with Chronic Myeloid Leukemia.

PMID- 29214764
TI  - Bone Marrow Involvement of Epstein-Barr Virus-Positive Large B-Cell Lymphoma in a
      Patient with Angioimmunoblastic T-Cell Lymphoma.

PMID- 29214765
TI  - Correlation of Aminoglycoside Consumption and Amikacin- or Gentamicin-Resistant
      Pseudomonas aeruginosa in Long-Term Nationwide Analysis: Is Antibiotic Cycling an
      Effective Policy for Reducing Antimicrobial Resistance?

PMID- 29214766
TI  - Abrupt Increase in Rate of Imipenem Resistance in Acinetobacter baumannii Complex
      Strains Isolated from General Hospitals in Korea and Correlation With Carbapenem
      Administration During 2002-2013.

PMID- 29214767
TI  - Catheter-related Bloodstream Infection due to Lodderomyces elongisporus in a
      Patient with Lung Cancer.

PMID- 29214768
TI  - Congenital Analbuminemia in Unrelated Algerian and Turkish Families is Caused by
      the Same Molecular Defect in the Albumin Gene.

PMID- 29214769
TI  - Preeminent Medical Missionary in the 20th Century: Oliver R. Avison.

PMID- 29214770
TI  - Disruption of the Gut Ecosystem by Antibiotics.
AB  - The intestinal microbiota is a complex ecosystem consisting of various
      microorganisms that expands human genetic repertoire and therefore affects human
      health and disease. The metabolic processes and signal transduction pathways of
      the host and intestinal microorganisms are intimately linked, and abnormal
      progression of each process leads to changes in the intestinal environment.
      Alterations in microbial communities lead to changes in functional structures
      based on the metabolites produced in the gut, and these environmental changes
      result in various bacterial infections and chronic enteric inflammatory diseases.
      Here, we illustrate how antibiotics are associated with an increased risk of
      antibiotic-associated diseases by driving intestinal environment changes that
      favor the proliferation and virulence of pathogens. Understanding the
      pathogenesis caused by antibiotics would be a crucial key to the treatment of
      antibiotic-associated diseases by mitigating changes in the intestinal
      environment and restoring it to its original state.

PMID- 29214771
TI  - Detection of Rare Mutations in EGFR-ARMS-PCR-Negative Lung Adenocarcinoma by
      Sanger Sequencing.
AB  - PURPOSE: This study aimed to identify potential epidermal growth factor receptor
      (EGFR) gene mutations in non-small cell lung cancer that went undetected by
      amplification refractory mutation system-Scorpion real-time PCR (ARMS-PCR).
      MATERIALS AND METHODS: A total of 200 specimens were obtained from the First
      Affiliated Hospital of Guangzhou Medical University from August 2014 to August
      2015. In total, 100 ARMS-negative and 100 ARMS-positive specimens were evaluated
      for EGFR gene mutations by Sanger sequencing. The methodology and sensitivity of
      each method and the outcomes of EGFR-tyrosine kinase inhibitor (TKI) therapy were
      analyzed. RESULTS: Among the 100 ARMS-PCR-positive samples, 90 were positive by
      Sanger sequencing, while 10 cases were considered negative, because the mutation
      abundance was less than 10%. Among the 100 negative cases, three were positive
      for a rare EGFR mutation by Sanger sequencing. In the curative effect analysis of
      EGFR-TKIs, the progression-free survival (PFS) analysis based on ARMS and Sanger
      sequencing results showed no difference. However, the PFS of patients with a high
      abundance of EGFR mutation was 12.4 months [95% confidence interval (CI), 11.6
      12.4 months], which was significantly higher than that of patients with a low
      abundance of mutations detected by Sanger sequencing (95% CI, 10.7-11.3 months)
      (p<0.001). CONCLUSION: The ARMS method demonstrated higher sensitivity than
      Sanger sequencing, but was prone to missing mutations due to primer design.
      Sanger sequencing was able to detect rare EGFR mutations and deemed applicable
      for confirming EGFR status. A clinical trial evaluating the efficacy of EGFR-TKIs
      in patients with rare EGFR mutations is needed.

PMID- 29214772
TI  - Pseudolaric Acid B Inhibits Proliferation, Invasion and Epithelial-to-Mesenchymal
      Transition in Human Pancreatic Cancer Cell.
AB  - PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B
      (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT)
      in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND
      METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB
      dose- and time-dependent manners. Cell proliferation and invasion ability were
      measured by MTT assay and Matrigel/Transwell test, respectively. Semi
      quantitative real-time polymerase chain reaction and Western blotting were
      conducted to detect the expression of EMT markers and the key molecules. Finally,
      nude mice subcutaneous transplantation tumor model was used to confirm the
      therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and
      invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin,
      Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p<0.01), while E
      cadherin, caspase-9, MST1, and pYAP were up-regulated (p<0.05). Combined PAB and
      gemcitabine treatment markedly restricted the tumor growth compared with
      gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation
      and invasion ability of pancreatic cancer cells through activating Hippo-YAP
      pathway and inhibiting the process of EMT.

PMID- 29214773
TI  - Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type
      Gastric Adenocarcinoma.
AB  - PURPOSE: Gastric cancer shows a male predominance that might be explained by
      protective effects from estrogens in females. Two Lauren classification
      histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The
      purpose of this study was to estimate the effects of sex hormone on female
      gastric cancer according to Lauren classification. MATERIALS AND METHODS: We
      reviewed medical records for and administered questionnaires, surveying
      reproductive and hormonal factors, to 758 patients who underwent gastrectomy for
      gastric cancer at Samsung Medical Center from May 2012 to November 2014.
      Clinicopathological characteristics were compared between females and males. The
      incidence of intestinal-type gastric cancer was compared between females
      subgroups, consist of premenopausal women and three groups of postmenopausal
      women (five-year intervals after menopause), and males. The association between
      reproductive factors and intestinal-type gastric cancer was analyzed by
      multivariate models for the female group. RESULTS: In total, 227 females (29.9%)
      and 531 males (70.9%) were included in the analysis. Undifferentiated
      adenocarcinoma and diffuse-type histology were more frequent in female patients
      than male patients. While 221 (41.6%) male patients had intestinal-type gastric
      cancer, no premenopausal female patient had this type of gastric cancer. The
      incidence of intestinal-type gastric cancer increased with time after menopause,
      and was similar to males after 10 years from menopause. Parity was associated
      with an increased risk of intestinal-type gastric cancer in menopausal women.
      CONCLUSION: These findings support that female sex hormones might be protective
      against intestinal-type gastric cancer.

PMID- 29214774
TI  - Correlation of Cancer Stem-Cell Markers OCT4, SOX2, and NANOG with
      Clinicopathological Features and Prognosis in Operative Patients with Rectal
      Cancer.
AB  - PURPOSE: To investigate the association of cancer stem-cell markers [octamer
      binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and
      Nanog homebox (NANOG)] expression with clinicopathological properties and overall
      survival (OS) in operative rectal cancer (RC) patients receiving adjuvant
      therapy. MATERIALS AND METHODS: 153 patients with primary RC receiving surgery
      were enrolled. Tumor tissue and paired adjacent normal tissue sample were
      collected, and OCT4, SOX2, and NANOG expressions were assessed by
      immunofluorescent staining. The median follow-up duration was 5.2 years, and the
      last follow-up date was August 2016. RESULTS: Tumor tissue OCT4 (p<0.001), SOX2
      (p=0.003), and NANOG (p<0.001) expressions were higher than those in adjacent
      tissue. OCT4 expression was positively correlated with pathological grade
      (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170,
      p=0.036). NANOG expression was positively associated with tumor size (R=0.169,
      p=0.036). Kaplan-Meier suggested that OCT4+ was associated with worse OS compared
      with OCT4? (p<0.001), while no association of SOX2 (p=0.121) and NANOG
      expressions (p=0.195) with OS was uncovered. Compared with one or no positive
      marker, at least two positive markers were associated with shorter OS (p<0.001),
      while all three positive markers were correlated with worse OS compared with two
      or less positive markers (p<0.001). Multivariate Cox's analysis revealed that
      OCT4+ (p<0.001) and N stage (p=0.046) were independent factors for shorter OS.
      CONCLUSION: Tumor tissue OCT4 expression was correlated with poor
      differentiation, tumor size, and N stage, and it can serve as an independent
      prognostic biomarker in operative patients with RC receiving adjuvant therapy.

PMID- 29214775
TI  - TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling.
AB  - PURPOSE: Tripartite-motif-containing protein 56 (TRIM56) has been found to
      exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we
      attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its
      underlying molecular basis. MATERIALS AND METHODS: TRIM56 expression at the mRNA
      and protein level was measured by qRT PCR and western blot analysis. 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry
      analysis was performed to investigate the effect of TRIM56 on MM cell
      proliferation and apoptosis. The concentrations of interferon (IFN)-beta,
      interleukin (IL)-6, and tumor necrosis factor-alpha in MM cell culture
      supernatants were detected with respective commercial ELISA kits. Western blot
      was employed to determine the effect of TRIM56 on toll-like receptor 3
      (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-beta
      (TRIF) signaling pathway. RESULTS: TRIM56 expression was prominently decreased in
      MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed
      proliferation, induced apoptosis, and enhanced inflammatory cytokine production,
      while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited
      inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown
      blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly
      abolished TRIM56 depletion-induced increase of proliferation, decrease of
      apoptosis, and reduction of inflammatory factor in MM cells. CONCLUSION: TRIM56
      may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling
      pathway, contributing to a better understanding of the molecular mechanism of
      TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy
      for patients with MM.

PMID- 29214776
TI  - 14-3-3zeta Overexpression is Associated with Poor Prognosis in Ovarian Cancer.
AB  - PURPOSE: 14-3-3zetaregulates cell signaling, cell cycle progression, and
      apoptosis, and its overexpression is associated with disease recurrence and poor
      clinical outcomes in some solid tumors. However, its clinicopathological role in
      ovarian cancer is unknown. Our goal was to investigate whether 14-3-3zetais
      associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3
      3zetaexpression by immunohistochemistry in ovarian cancer tissues obtained from
      88 ovarian cancer patients. The examined tissues were of various histologies and
      stages. 14-3-3zetaexpression was also analyzed by western blot in seven ovarian
      cancer cell lines and a primary ovary epithelial cell line. Cell viability was
      measured using an MTS-based assay following cisplatin treatment. RESULTS: Among
      the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3zetaexpression, and
      14-3-3zetaoverexpression was positively correlated with more advanced pathologic
      stages and grades. 14-3-3zetaoverexpression was also significantly associated
      with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer
      patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14
      3-3zetaexpression group, but not reached in the low 14-3-3zetaexpression group
      (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3zetaby
      RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin
      induced cell death. CONCLUSION: 14-3-3zetaoverexpression might be a potential
      prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3zetacould be
      a therapeutic option that enhances the antitumor activity of cisplatin.

PMID- 29214777
TI  - Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart
      Failure? Sex-Related Difference in the Obesity Paradox.
AB  - PURPOSE: Obesity is often associated with better clinical outcomes in heart
      failure (HF). This so-called obesity paradox remains controversial. The aim of
      present study was to investigate the prognostic value of obesity in patients
      hospitalized for systolic HF. MATERIALS AND METHODS: We performed a pooled
      analysis of data from two multicenter, observational HF studies. Patients
      hospitalized for systolic HF were eligible for the present study. We divided the
      subjects into two groups, a normal body mass index (BMI) group and a high BMI
      group. Study endpoints included all-cause mortality and any re-hospitalization
      within 1 year. RESULTS: We enrolled 3145 patients (male, 1824; female, 1321). The
      high BMI group was significantly associated with lower 1-year mortality rate
      [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355-0.832] after
      adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial
      infarction, serum creatinine level, anemia, and ejection fraction in men. After
      adjustment for clinical characteristics, high BMI was not significantly
      associated with 1-year mortality (OR, 0.739; 95% CI, 0.450-1.216) or 1-year re
      hospitalization (OR, 0.958; 95% CI, 0.696-1.319) in women. CONCLUSION: In pooled
      analysis of data from two Korean HF registries, the high BMI group was
      independently associated with lower 1-year mortality rate from systolic HF,
      especially in men.

PMID- 29214778
TI  - Supplementary Diagnostic Landmarks of Left Ventricular Non-Compaction on Magnetic
      Resonance Imaging.
AB  - PURPOSE: Diagnostic criteria for left ventricular non-compaction (LVNC) are still
      a matter of dispute. The aim of our present study was to test the diagnostic
      value of two novel diagnostic cardiac magnetic resonance (CMR) parameters: proof
      of non-compact (NC) myocardium blood flow using T2 sequences and changes in
      geometry of the left ventricle. MATERIALS AND METHODS: The study included cases
      with LVNC and controls, from a data base formed in a period of 3.5 years (n=1890
      exams), in which CMR protocol included T2 sequences. Measurement of perpendicular
      maximal and minimal end diastolic dimensions in the region with NC myocardium
      from short axis plane was recorded, and calculated as a ratio (MaxMinEDDR), while
      flow through trabecula was proven by intracavital T2-weighted hyperintensity
      (ICT2HI). LVNC diagnosis met the following three criteria: thickening of compact
      (C) layer, NC:C>2.3:1 and NC>20%LV. RESULTS: The study included 200 patients; 71
      with LVNC (35.5%; i.e., 3.76% of CMRs) and 129 (64.5%) controls. MaxMinEDDR in
      patients with LVNC was significantly different from that in controls (1.17+/-0.08
      vs. 1.06+/-0.04, respectively; p<0.001). MaxMinEDDR >1.10 had sensitivity of
      91.6% [95% confidence intervals (CI) 82.5-96.8], specificity of 85.3% (95% CI
      78.0-90.0), and area under curve (AUC) 0.919 (95% CI 0.872-0.953; p<0.001) for
      LVNC. Existence of ICT2HI had sensitivity of 100.0% (95% CI 94.9-100.0),
      specificity of 91.5% (95% CI 85.3-95.7), and AUC 0.957 (95% CI 0.919-0.981;
      p<0.001) for LVNC. CONCLUSION: Two additional diagnostic parameters for LVNC were
      identified in this study. ICT2HI and geometric eccentricity of the ventricle both
      had relatively high sensitivity and specificity for diagnosing LVNC.

PMID- 29214780
TI  - Mismatch between TOF MR Angiography and CT Angiography of the Middle Cerebral
      Artery may be a Critical Sign in Cerebrovascular Dynamics.
AB  - PURPOSE: Although time-of-flight (TOF)-magnetic resonance angiography (MRA) can
      clearly depict intracranial arteries, the arterial flow of middle cerebral artery
      (MCA) is occasionally not detected. We evaluated this phenomenon with reference
      to cerebrovascular dynamics. MATERIALS AND METHODS: Seventeen patients with
      suspected occlusion of MCA or internal carotid artery on TOF-MRA were enrolled.
      All patients underwent CT angiography (CTA) and quantitative cerebral blood flow
      (CBF) examination for measurement of resting CBF and cerebrovascular reactivity
      (CVR). Depending on appearance, patients were categorized into three groups.
      Group A (n=6) had MCA delineation on both MRA and CTA, while groups B (n=6) and C
      (n=5) had no signal on MRA, but Group B had a MCA delineation on CTA. RESULTS: No
      significant difference between resting CBF and CBF after the administration of
      acetazolamide was seen among 3 groups. In contrast, mean CVR in group B was 
      19.7+/-18.1%, which was significantly lower than group A [36.4+/-21.7% (p<0.05)],
      but not than group C (21.4+/-35.2%). Furthermore, all patients in group B
      displayed a so-called steal phenomenon. CONCLUSION: This study is the first to
      show that visualization of MCA on TOF-MRA closely correlates with CVR, and that a
      vascular pattern showing no MCA signal intensity on MRA but with MCA delineation
      on CTA indicates a critical cerebrovascular condition.

PMID- 29214779
TI  - Effectiveness and Safety of Biolimus A9TM-Eluting stEnt in Patients with AcUTe
      Coronary sYndrome; A Multicenter, Observational Study (BEAUTY Study).
AB  - PURPOSE: This study sought to determine the 1-year clinical effectiveness and
      safety of a biodegradable, polymer-containing Biolimus A9TM-eluting stent (BES)
      in Korean patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A
      total of 1000 ACS patients with 1251 lesions who underwent implantation of BESs
      at 22 centers in Korea were enrolled between May 2011 and July 2013. We assessed
      major adverse cardiac events (MACE) defined as the composite of cardiac death,
      non-fatal myocardial infarction (MI), and clinical-driven target vessel
      revascularization at 12 months. RESULTS: Patient mean age was 62.6+/-11.4 years.
      72.8% of the patients were male, 28.5% had diabetes, 32.8% had multi-vessel
      disease (MVD), and 47.9% presented with acute MI (AMI). The mean global registry
      of acute coronary events risk score of all patients was 103.0+/-27.6. The number
      of stents per patient was 1.3+/-0.6. The incidences of MACE and definite stent
      thrombosis at 12 months were 3.9% and 0.2%, respectively. On multivariate Cox
      regression analysis, age >=65 years was identified as an independent predictors
      of 1-year MACE (hazard ratio=2.474; 95% confidence interval=1.202-5.091).
      Subgroup analyses revealed no significant differences in the incidence of MACE
      between patients with and without diabetes (4.3% vs. 3.7%, p=0.667), between
      those who presented with and without AMI (4.4% vs. 3.4%, p=0.403), and between
      those with and without MVD (4.6% vs. 3.5%, p=0.387). CONCLUSION: Our study
      demonstrated excellent 1-year clinical outcomes of BES implantation in patients
      at low-risk for ACS.

PMID- 29214781
TI  - Adipogenic and Lipolytic Effects of Ascorbic Acid in Ovariectomized Rats.
AB  - PURPOSE: Ascorbic acid has been reported to have an adipogenic effect on 3T3-L1
      preadipocytes, while evidence also suggests that ascorbic acid reduces body
      weight in humans. In this study, we tested the effects of ascorbic acid on
      adipogenesis and the balance of lipid accumulation in ovariectomized rats, in
      addition to long-term culture of differentiated 3T3-L1 adipocytes. MATERIALS AND
      METHODS: Murine 3T3-L1 fibroblasts and ovariectomized rats were treated with
      ascorbic acid at various time points. In vitro adipogenesis was analyzed by Oil
      Red O staining, and in vivo body fat was measured by a body composition analyzer
      using nuclear magnetic resonance. RESULTS: When ascorbic acid was applied during
      an early time point in 3T3-L1 preadipocyte differentiation and after bilateral
      ovariectomy (OVX) in rats, adipogenesis and fat mass gain significantly
      increased, respectively. However, lipid accumulation in well-differentiated 3T3
      L1 adipocytes showed a significant reduction when ascorbic acid was applied after
      differentiation (10 days after induction). Also, oral ascorbic acid
      administration 4 weeks after OVX in rats significantly reduced both body weight
      and subcutaneous fat layer. In comparison to the results of ascorbic acid, which
      is a well-known cofactor for an enzyme of collagen synthesis, and the antioxidant
      ramalin, a potent antioxidant but not a cofactor, showed only a lipolytic effect
      in well-differentiated 3T3-L1 adipocytes, not an adipogenic effect. CONCLUSION:
      Taking these results into account, we concluded that ascorbic acid has both an
      adipogenic effect as a cofactor of an enzymatic process and a lipolytic effect as
      an antioxidant.

PMID- 29214782
TI  - Effect of Family History of Diabetes on Hemoglobin A1c Levels among Individuals
      with and without Diabetes: The Dong-gu Study.
AB  - PURPOSE: We investigated associations between family history of diabetes (FHD)
      and hemoglobin A1c (HbA1c) level, among people with and without diabetes.
      MATERIALS AND METHODS: In total, 7031 people without diabetes and 1918 people
      with diabetes who participated in the Dong-gu Study were included. Data on FHD in
      first-degree relatives (father, mother, and siblings) were obtained. Elevated
      HbA1c levels in people without diabetes and high HbA1c levels in people with
      diabetes were defined as the highest quintiles of HbA1c >=5.9% and >=7.9%,
      respectively. RESULTS: In people without diabetes, the odds of elevated HbA1c
      levels [odds ratio (OR) 1.34, 95% confidence interval (CI) 1.13-1.59] were
      significantly greater in people with any FHD than in those without. Specifically,
      the odds of elevated HbA1c levels in people without diabetes with an FHD
      involving siblings were greater than in those without an FHD involving siblings.
      Additionally, in people with diabetes, the odds of high HbA1c levels (OR 1.33,
      95% CI 1.02-1.72) were greater in people with any FHD than in those without such
      history. Moreover, people with diabetes with maternal FHD had increased odds of
      high HbA1c levels. CONCLUSION: FHD was associated not only with high HbA1c levels
      in people with diabetes, but also with elevated HbA1c levels in people without
      diabetes.

PMID- 29214783
TI  - Effective Tidal Volume for Normocapnia in Very-Low-Birth-Weight Infants Using
      High-Frequency Oscillatory Ventilation.
AB  - PURPOSE: Removal of CO2 is much efficient during high-frequency oscillatory
      ventilation (HFOV) for preterm infants. However, an optimal carbon dioxide
      diffusion coefficient (DCO2) and tidal volume (VT) have not yet been established
      due to much individual variance. This study aimed to analyze DCO2 values, VT, and
      minute volume in very-low-birth-weight (VLBW) infants using HFOV and correlates
      with plasma CO2 (pCO2). MATERIALS AND METHODS: Daily respiratory mechanics and
      ventilator settings from twenty VLBW infants and their two hundred seventeen
      results of blood gas analysis were collected. Patients were treated with the
      Drager Babylog VN500 ventilator (Dragerwerk Ag & Co.) in HFOV mode. The
      normocapnia was indicated as pCO2 ranging from 45 mm Hg to 55 mm Hg. RESULTS: The
      measured VT was 1.7 mL/kg, minute volume was 0.7 mL/kg, and DCO2 was 43.5 mL2/s.
      Mean results of the blood gas test were as follows: pH, 7.31; pCO2, 52.6 mm Hg;
      and SpO2, 90.5%. In normocapnic state, the mean VT was significantly higher than
      in hypercapnic state (2.1+/-0.5 mL/kg vs. 1.6+/-0.3 mL/kg), and the mean DCO2
      showed significant difference (68.4+/-32.7 mL2/s vs. 32.4+/-15.7 mL2/s). The DCO2
      was significantly correlated with the pCO2 (p=0.024). In the receiver operating
      curve analysis, the estimated optimal cut-off point to predict the remaining
      normocapnic status was a VT of 1.75 mL/kg (sensitivity 73%, specificity 80%).
      CONCLUSION: In VLBW infants treated with HFOV, VT of 1.75 mL/kg is recommended
      for maintaining proper ventilation.

PMID- 29214784
TI  - Contrast-Induced Acute Kidney Injury after Coil Embolization for Aneurysmal
      Subarachnoid Hemorrhage.
AB  - PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is associated with poor
      outcomes after percutaneous coronary intervention. However, CI-AKI has rarely
      been evaluated within the neurovascular field. The aim of this study was to
      investigate the incidence and clinical implication of CI-AKI after coil
      embolization in patients with an aneurysmal subarachnoid hemorrhage (aSAH).
      MATERIALS AND METHODS: Between January 2005 and March 2016, 192 patients who
      underwent coil embolization were enrolled in this study. CI-AKI was defined as an
      increase from baseline serum creatinine concentration of >25% or >0.5 mg/dL
      within 72 hours after coil embolization. A poor clinical outcome was defined as a
      score of >=3 on the modified Rankin Scale at one-year post-treatment. RESULTS: A
      total of 16 patients (8.3%) died as a result of medical problems within one year.
      CI-AKI was identified in 14 patients (7.3%). Prominent risk factors for one-year
      mortality included CI-AKI [odds ratio (OR): 16.856; 95% confidence interval (CI):
      3.437-82.664] and an initial Glasgow Coma Scale (GCS) score <=8 (OR: 5.565; 95%
      CI: 1.703-18.184). A poor clinical outcome was associated with old age (>=65
      years) (OR: 7.921; 95% CI: 2.977-21.076), CI-AKI (OR: 11.281; 95% CI: 2.138
      59.525), an initial GCS score <=8 (OR 31.02; 95% CI, 10.669-90.187), and a
      ruptured aneurysm (p=0.016, OR: 4.278) in posterior circulation. CONCLUSION: CI
      AKI seems to be an independent predictor of the overall outcomes of aSAH after
      endovascular treatment.

PMID- 29214785
TI  - Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for
      Intravenous Immunoglobulin-Resistant Kawasaki Disease.
AB  - PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki
      disease (KD). However, there is still no standard treatment for IVIG-resistant
      KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a
      treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively
      analyzed 10-year data for patients with IVIG-resistant KD who were administered
      MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients
      with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum
      body temperatures decreased significantly within 24 h of therapy. The patients' C
      reactive protein levels were significantly lower 1 week after administering the
      first dose of MTX than those before treatment. No adverse effect for MTX was
      observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid
      defervescence, improvement of clinical symptoms, and normalization of acute-phase
      reactants in all patients. Thus, MTX could be a candidate treatment for IVIG
      resistant KD.

PMID- 29214786
TI  - ITPKC and SLC11A1 Gene Polymorphisms and Gene-Gene Interactions in Korean
      Patients with Kawasaki Disease.
AB  - PURPOSE: Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology
      of KD and the erythema of Bacille Calmette-Guerin (BCG) injection sites observed
      in the disease are poorly understood. We investigated the association between KD
      and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5
      triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute
      carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to
      the BCG strain in Koreans. MATERIALS AND METHODS: Associations between KD and
      SNPs in two genes were evaluated. Potential associations between BCG injection
      site erythema and SNPs in two genes were also evaluated. Gene-gene interactions
      between ITPKC and SLC11A1 in KD and BCG injection site erythema were also
      analyzed. RESULTS: Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1
      were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in
      ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in
      SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG
      injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated
      with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions
      between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC
      rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG
      injection site erythema. CONCLUSION: This study identified several important
      polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants
      identified in this study affected KD and erythema of BCG injection sites
      independently and through gene-gene interactions. Also, the effects of the
      polymorphisms were age-dependent.

PMID- 29214787
TI  - Myocardial Layer-Specific Strain Analysis in Children with Mitochondrial Disease.
AB  - PURPOSE: Children with mitochondrial disease (MD) have clinical phenotypes that
      are more severe than those found in adults. In this study, we assessed cardiac
      function in children with MD using conventional and advanced echocardiographic
      measurements, explored any unique patterns present, and investigated the
      development of early cardiomyopathy (CMP). MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of 33 children with MD. All patients
      underwent transthoracic echocardiography with conventional and advanced
      myocardial analysis. We compared all data between patients and an age-matched
      healthy control group. RESULTS: Conventional echocardiographic diastolic
      measurements of mitral E, E/A, and tissue Doppler E' were significantly lower and
      E/E' was significantly higher in children with MD, compared with the measurements
      from the control group. There was no significant difference in longitudinal and
      radial strain between the groups. Circumferential strain in the endocardium
      (p=0.161), middle myocardium (p=0.008), and epicardium (p=0.042) were lower in
      patients, compared to the values in controls. Circumferential strain was
      correlated with E' (p<0.01, r>0.60). CONCLUSION: In children with MD, myocardial
      circumferential strain may develop early in all three layers, even with normally
      preserved longitudinal and radial strain. This may be an early diagnostic
      indicator with which to predict CMP in this patient population.

PMID- 29214788
TI  - Asymmetry of Peak Thicknesses between the Superior and Inferior Retinal Nerve
      Fiber Layers for Early Glaucoma Detection: A Simple Screening Method.
AB  - PURPOSE: To assess whether the asymmetry in the peripapillary retinal nerve fiber
      layer (pRNFL) thickness between superior and inferior hemispheres on optical
      coherence tomography (OCT) is useful for early detection of glaucoma. MATERIALS
      AND METHODS: The patient population consisted of Training set (a total of 60
      subjects with early glaucoma and 59 normal subjects) and Validation set (30
      subjects with early glaucoma and 30 normal subjects). Two kinds of ratios were
      employed to measure the asymmetry between the superior and inferior pRNFL
      thickness using OCT. One was the ratio of the superior to inferior peak
      thicknesses (peak pRNFL thickness ratio; PTR), and the other was the ratio of the
      superior to inferior average thickness (average pRNFL thickness ratio; ATR). The
      diagnostic abilities of the PTR and ATR were compared to the color code
      classification in OCT. Using the optimal cut-off values of the PTR and ATR
      obtained from the Training set, the two ratios were independently validated for
      diagnostic capability. RESULTS: For the Training set, the
      sensitivities/specificities of the PTR, ATR, quadrants color code classification,
      and clock-hour color code classification were 81.7%/93.2%, 71.7%/74.6%,
      75.0%/93.2%, and 75.0%/79.7%, respectively. The PTR showed a better diagnostic
      performance for early glaucoma detection than the ATR and the clock-hour color
      code classification in terms of areas under the receiver operating characteristic
      curves (AUCs) (0.898, 0.765, and 0.773, respectively). For the Validation set,
      the PTR also showed the best sensitivity and AUC. CONCLUSION: The PTR is a simple
      method with considerable diagnostic ability for early glaucoma detection. It can,
      therefore, be widely used as a new screening method for early glaucoma.

PMID- 29214789
TI  - microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in
      Zebrafish.
AB  - PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides
      that regulate development and differentiation in various organs by silencing
      specific RNAs and regulating gene expression. In the present study, we show that
      the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and
      that its inhibition reduces hair cell regeneration following neomycin-induced
      ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after
      neomycin exposure were analyzed using microarray chips. Quantitative polymerase
      chain reaction was performed to validate miR-183 cluster expression patterns
      following neomycin exposure (500 MUM for 2 h). After injection of an antisense
      morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell
      regeneration after neomycin exposure in neuromast cells was evaluated by
      fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic
      zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair
      cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR
      96, miR-182, and miR-183) was upregulated after neomycin treatment. We also
      confirmed upregulated expression of the miR-183 cluster during hair cell
      regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183
      reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish
      larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential
      for the regeneration of hair cells following ototoxic injury in zebrafish larvae.
      Therefore, regulation of the miR-183 cluster can be a novel target for
      stimulation of hair cell regeneration.

PMID- 29214790
TI  - Variants of Lipolysis-Related Genes in Korean Patients with Very High
      Triglycerides.
AB  - We investigated the prevalence and characteristics of variants of five lipolysis
      related genes in Korean patients with very high triglycerides (TGs). Twenty-six
      patients with TG levels >885 mg/dL were selected from 13545 Korean subjects. Five
      candidate genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1, were sequenced by targeted
      next-generation sequencing. Predictions of functional effects were performed and
      matched against public databases of variants. Ten rare variants of three genes
      were found in nine (34.6%) patients (three in LPL, four in APOA5, and three in
      LMF1). Five were novel and all variants were suspected of being disease-causing.
      Nine were heterozygous, and one (3.8%) had a homozygous rare variant of LPL. Six
      common variants of four genes were observed in 25 (96.2%) patients (one in LPL,
      one in GPIHBP1, two in APOA5, and two in LMF1). The c.G41T variant of GPIHBP1 and
      c.G533T variant of APOA5 were most frequent and found in 15 (57.7%) and 14
      (53.8%) patients, respectively. Rare homozygous variants of the genes were very
      uncommon, while diverse rare heterozygous variants were commonly identified.
      Taken together, most study subjects may be manifesting the combined effects of
      rare heterozygous variants and common variants.

PMID- 29214791
TI  - A Case of Schnitzler's Syndrome without Monoclonal Gammopathy-Associated Chronic
      Urticaria Treated with Anakinra.
AB  - Chronic urticaria may often be associated with interleukin (IL)-1-mediated
      autoinflammatory disease, which should be suspected if systemic inflammation
      signs are present. Here, we report a case of Schnitzler's syndrome without
      monoclonal gammopathy treated successfully with the IL-1 receptor antagonist
      anakinra. A 69-year-old man suffered from a pruritic urticarial rash for 12
      years. It became aggravated episodically and was accompanied by high fever,
      arthralgia, leukocytosis, and an elevated C-reactive protein and erythrocyte
      sedimentation rate. The episodes each lasted for over one week. Neutrophilic and
      eosinophilic inflammation was found on skin biopsy. However, serum and urine
      electrophoresis showed no evidence of monoclonal gammopathy. The cutaneous
      lesions were unresponsive to various kinds of anti-histamines, systemic
      glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate, which were
      administered over a span of 3 years immediately preceding successful treatment. A
      dramatic response, however, was observed after a daily administration of
      anakinra. This observation suggests that the correct diagnosis of this case is
      Schnitzler's syndrome without monoclonal gammopathy. For an adult patient with
      refractory chronic urticaria and systemic inflammation, Schnitzler's syndrome
      could be considered as a possible differential diagnosis. Although the typical
      form of Schnitzler's syndrome exhibits the presence of monoclonal gammopathy as a
      diagnostic criterion, monoclonal gammopathy may be absent in an atypical form. In
      such a situation, an IL-1 antagonist should be effective for the management of
      chronic urticaria.

PMID- 29214792
TI  - Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion.
AB  - Radiocontrast media-induced acute severe thrombocytopenia is a very rare
      complication and potentially life-threatening. Here, we report the case of a 63
      year-old male patient with severe acute thrombocytopenia following first exposure
      to intravenous non-ionic contrast media without immediate allergic reactions. His
      platelet count dropped from 107000/MUL to 2000/MUL after six hours of
      radiocontrast infusion. After administration of corticosteroid and transfusion of
      platelet concentrates, the platelet count returned gradually to normal within 5
      days. To the best of our knowledge, non-ionic contrast media-induced isolated
      acute severe thrombocytopenia following no signs or symptoms of immediate
      allergic reaction has never been described.

PMID- 29214793
TI  - Mesocaval Shunt Creation for Jejunal Variceal Bleeding with Chronic Portal Vein
      Thrombosis.
AB  - The creation of transjugular intrahepatic portosystemic shunt (TIPS) is a widely
      performed technique to relieve portal hypertension, and to manage recurrent
      variceal bleeding and refractory ascites in patients where medical and/or
      endoscopic treatments have failed. However, portosystemic shunt creation can be
      challenging in the presence of chronic portal vein occlusion. In this case
      report, we describe a minimally invasive endovascular mesocaval shunt creation
      with transsplenic approach for the management of recurrent variceal bleeding in a
      portal hypertension patient with intra- and extrahepatic portal vein occlusion.

PMID- 29214795
TI  - Retraction: Paper "Comparison of the Effect of Vitamin K2 and Risedronate on
      Trabecular Bone in Glucocorticoid-Treated Rats: A Bone Histomorphometry Study" by
      Iwamoto J, et al. [Yonsei Med J 2009;50(2):189-194].
AB  - [This retracts the article DOI: 10.3349/ymj.2009.50.2.189.].

PMID- 29214794
TI  - Retraction: Paper "Comparison of Effects of Alendronate and Raloxifene on Lumbar
      Bone Mineral Density, Bone Turnover, and Lipid Metabolism in Elderly Women with
      Osteoporosis" by Iwamoto J, et al. [Yonsei Med J 2008;49(1):119-128].
AB  - [This retracts the article DOI: 10.3349/ymj.2008.49.1.119.].

PMID- 29214796
TI  - Grey matter correlates of autistic traits in women with anorexia nervosa
AB  - Background: Patients with anorexia nervosa exhibit higher levels of behaviours
      typically associated with autism-spectrum disorder (ASD), but the neural basis is
      unclear. We sought to determine whether elevated autistic traits in women with
      anorexia nervosa may be reflected in cortical morphology. Methods: We used voxel
      based morphometry (VBM) to examine regional grey matter volumes in high
      resolution MRI structural brain scans in women with anorexia nervosa and matched
      healthy controls. The Autism-spectrum Quotient (AQ) scale was used to assess
      autistic traits. Results: Women with anorexia nervosa (n = 25) had higher AQ
      scores and lower bilateral superior temporal sulcus (STS) grey matter volumes
      than the control group (n = 25). The AQ scores correlated negatively with average
      left STS grey matter volume in women with anorexia nervosa. Limitations: We did
      not control for cognitive ability and examined only women with ongoing anorexia
      nervosa. Conclusion: Elevated autistic traits in women with anorexia nervosa are
      associated with morphometric alterations of brain areas linked to social
      cognition. This finding provides neurobiological support for the behavioural link
      between anorexia nervosa and ASD and emphasizes the importance of recognizing
      autistic traits in preventing and treating -anorexia nervosa.

PMID- 29214797
TI  - High-throughput in Vitro Data To Inform Prioritization of Ambient Water
      Monitoring and Testing for Endocrine Active Chemicals.
AB  - The presence of industrial chemicals, consumer product chemicals, and
      pharmaceuticals is well documented in waters in the U.S. and globally. Most of
      these chemicals lack health-protective guidelines and many have been shown to
      have endocrine bioactivity. There is currently no systematic or national
      prioritization for monitoring waters for chemicals with endocrine disrupting
      activity. We propose ambient water bioactivity concentrations (AWBCs) generated
      from high throughput data as a health-based screen for endocrine bioactivity of
      chemicals in water. The U.S. EPA ToxCast program has screened over 1800 chemicals
      for estrogen receptor (ER) and androgen receptor (AR) pathway bioactivity. AWBCs
      are calculated for 110 ER and 212 AR bioactive chemicals using high throughput
      ToxCast data from in vitro screening assays and predictive pathway models, high
      throughput toxicokinetic data, and data-driven assumptions about consumption of
      water. Chemical-specific AWBCs are compared with measured water concentrations in
      data sets from the greater Denver area, Minnesota lakes, and Oregon waters,
      demonstrating a framework for identifying endocrine bioactive chemicals. This
      approach can be used to screen potential cumulative endocrine activity in
      drinking water and to inform prioritization of future monitoring, chemical
      testing and pollution prevention efforts.

PMID- 29214798
TI  - Gecko-Inspired Dry Adhesive Based on Micro-Nanoscale Hierarchical Arrays for
      Application in Climbing Devices.
AB  - The unusual ability of geckos to climb vertical walls underlies a unique
      combination of a hierarchical structural design and a stiffer material
      composition. While a dense array of microscopic hierarchical structures enables
      the gecko toe pads to adhere to various surfaces, a stiffer material (beta
      keratin) composition enables them to maintain reliable adhesion over innumerable
      cycles. This unique strategy has been seldom implemented in engineered dry
      adhesives because fabrication of high-aspect-ratio hierarchical structures using
      a stiffer polymer is challenging. Herein, we report the fabrication of high
      aspect-ratio hierarchical arrays on flexible polycarbonate sheets (stiffness
      comparable to that of beta-keratin) by a sacrificial-layer-mediated
      nanoimprinting technique. Dry-adhesive films comprising the hierarchical arrays
      showed a formidable shear adhesion of 11.91 +/- 0.43 N/cm2. Cyclic adhesion tests
      also showed that the shear adhesion of the adhesive films reduced by only about
      20% after 50 cycles and remained nearly constant until about 200 cycles. Most
      importantly, the high-aspect-ratio hierarchical arrays were integrated onto the
      feet of a miniature robot and the locomotion on a 30 degrees  inclined surface
      was demonstrated.

PMID- 29214799
TI  - Advanced Multiwavelength Detection in Analytical Ultracentrifugation.
AB  - This work highlights significant advancements in detector hardware and software
      for multiwavelength analytical ultracentrifugation (MWL-AUC) experiments,
      demonstrating improvement in both the spectral performance and UV capabilities of
      the instrument. The hardware is an extension of the Open AUC MWL detector
      developed in academia and first introduced in 2006 by Bhattacharya et al.
      Additional modifications as well as new analytical methods available for MWL data
      have since been reported. The present work describes new and continuing
      improvements to the MWL detector, including mirror source and imaging optics, UV
      sensitive acquisition modes and revised data acquisition software. The marked
      improvement of experimental data promises to provide access to increasingly
      complex systems, especially semiconductor nanoparticles, synthetic polymers,
      biopolymers, and other chromophores absorbing in the UV. Details of the detection
      system and components are examined to reveal the influences on data quality and
      to guide further developments. The benchmark comparisons of data quality across
      platforms will also serve as a reference guide for evaluation of forthcoming
      commercial absorbance optics.

PMID- 29214800
TI  - Cu(II)-Mediated Decarboxylative Trifluoromethylthiolation of alpha,beta
      Unsaturated Carboxylic Acids.
AB  - A tunable method for the direct trifluoromethylthiolation of alpha,beta
      unsaturated carboxylic acids was developed to afford trifluoromethylthiolated
      ketones or alkenes. The reaction proceeds smoothly under mild conditions and
      shows an excellent functional group tolerance.

PMID- 29214801
TI  - Increases of Total Mercury and Methylmercury Releases from Municipal Sewage into
      Environment in China and Implications.
AB  - As a globally transported pollutant, mercury (Hg) released from human activity
      and methylmercury (MeHg) in the food web are global concerns due to their
      increasing presence in the environment. In this study, we found that Hg released
      from municipal sewage into the environment in China is a substantial
      anthropogenic source based on mass sampling throughout China. In total, 160 Mg
      (140-190 Mg, from the 20th percentile to the 80th percentile) of Hg (THg) and 280
      kg (240-330 kg) of MeHg were released from municipal sewage in China in 2015. The
      quantities of released THg and MeHg were the most concentrated in the coastal
      regions, especially in the East, North and South China regions. However, the per
      capita release of THg and MeHg was the highest in the Tibetan region, which is
      recognized as the cleanest region in China. THg released into aquatic
      environments was mitigated from 2001 to 2015 in China, but the amounts released
      into other sinks increased. This study provides the first picture of the release
      of Hg from municipal sewage into various sinks in China, and policy makers should
      pay more attention to the diversity and complexity of the sources and transport
      of Hg, which can lead to Hg accumulation in the food web and can threaten human
      health.

PMID- 29214802
TI  - Trimethylamine N-oxide Counteracts Urea Denaturation by Inhibiting Protein-Urea
      Preferential Interaction.
AB  - Osmolytes are small organic molecules that can modulate the stability and
      function of cellular proteins by altering the chemical environment of the cell.
      Some of these osmolytes work in conjunction, via mechanisms that are poorly
      understood. An example is the naturally occurring protein-protective osmolyte
      trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine
      organisms against the detrimental denaturing effects of another naturally
      occurring osmolyte, urea. From a computational standpoint, our understanding of
      this counteraction mechanism is hampered by the fact that existing force fields
      fail to capture the correct balance of TMAO and urea interactions in ternary
      solutions. Using molecular dynamics simulations and Kirkwood-Buff theory of
      solutions, we have developed an optimized force field that reproduces
      experimental Kirkwood-Buff integrals. We show through the study of two model
      systems, a 15-residue polyalanine chain and the R2-fragment (273GKVQIINKKLDL284)
      of the Tau protein, that TMAO can counteract the denaturing effects of urea by
      inhibiting protein-urea preferential interaction. The extent to which
      counteraction can occur is seen to depend heavily on the amino acid composition
      of the peptide.

PMID- 29214803
TI  - Shear-Thinning and Thermo-Reversible Nanoengineered Inks for 3D Bioprinting.
AB  - Three-dimensional (3D) printing is an emerging approach for rapid fabrication of
      complex tissue structures using cell-loaded bioinks. However, 3D bioprinting has
      hit a bottleneck in progress because of the lack of suitable bioinks that are
      printable, have high shape fidelity, and are mechanically resilient. In this
      study, we introduce a new family of nanoengineered bioinks consisting of kappa
      carrageenan (kappaCA) and two-dimensional (2D) nanosilicates (nSi). kappaCA is a
      biocompatible, linear, sulfated polysaccharide derived from red algae and can
      undergo thermo-reversible and ionic gelation. The shear-thinning characteristics
      of kappaCA were tailored by nanosilicates to develop a printable bioink. By
      tuning kappaCA-nanosilicate ratios, the thermo-reversible gelation of the bioink
      can be controlled to obtain high printability and shape retention
      characteristics. The unique aspect of the nanoengineered kappaCA-nSi bioink is
      its ability to print physiologically-relevant-scale tissue constructs without
      requiring secondary supports. We envision that nanoengineered kappaCA
      nanosilicate bioinks can be used to 3D print complex, large-scale, cell-laden
      tissue constructs with high structural fidelity and tunable mechanical stiffness
      for regenerative medicine.

PMID- 29214804
TI  - Novel Biology and Druggable Targets via Chemoproteomics.

PMID- 29214805
TI  - Prediction of the Formation of Biogenic Nonextractable Residues during
      Degradation of Environmental Chemicals from Biomass Yields.
AB  - Degradation tests with radio or stable isotope labeled compounds enable the
      detection of the formation of nonextractable residues (NER). In PBT and vPvB
      assessment, remobilisable NER are considered as a potential risk while biogenic
      NER from incorporation of labeled carbon into microbial biomass are treated as
      degradation products. Relationships between yield, released CO2 (as indicator of
      microbial activity and mineralization) and microbial growth can be used to
      estimate the formation of biogenic NER. We provide a new approach for calculation
      of potential substrate transformation to microbial biomass (theoretical yield)
      based on Gibbs free energy and microbially available electrons. We compare
      estimated theoretical yields of biotechnological substrates and of chemicals of
      environmental concern with experimentally determined yields for validation of the
      presented approach. A five-compartment dynamic model is applied to simulate
      experiments of 13C-labeled 2,4-D and ibuprofen turnover. The results show that
      bioNER increases with time, and that most bioNER originates from microbial
      proteins. Simulations with precalculated input data demonstrate that
      precalculation of yields reduces the number of fit parameters considerably,
      increases confidence in fitted kinetic data, and reduces the uncertainty of the
      simulation results.

PMID- 29214806
TI  - Hierarchical Superhydrophobic Surfaces with Micropatterned Nanowire Arrays for
      High-Efficiency Jumping Droplet Condensation.
AB  - Self-propelled droplet jumping on nanostructured superhydrophobic surfaces is of
      interest for a variety of industrial applications including self-cleaning, water
      harvesting, power generation, and thermal management systems. However, the
      uncontrolled nucleation-induced Wenzel state of condensed droplets at large
      surface subcooling (high heat flux) leads to the formation of unwanted large
      pinned droplets, which results in the flooding phenomenon and greatly degrades
      the heat transfer performance. In this work, we present a novel strategy to
      manipulate droplet behaviors during the process from the droplet nucleation to
      growth and departure through a combination of spatially controlling initial
      nucleation for mobile droplets by closely spaced nanowires and promoting the
      spontaneous outward movement of droplets for rapid removal using micropatterned
      nanowire arrays. Through the optical visualization experiments and heat transfer
      tests, we demonstrate greatly improved condensation heat transfer characteristics
      on the hierarchical superhydrophobic surface including the higher density of
      microdroplets, smaller droplet departure radius, 133% wider range of surface
      subcooling for droplet jumping, and 37% enhancement in critical heat flux for
      jumping droplet condensation, compared to the-state-of-art jumping droplet
      condensation on nanostructured superhydrophobic surfaces. The excellent water
      repellency of such hierarchical superhydrophobic surfaces can be promising for
      many potential applications, such as anti-icing, antifogging, water desalination,
      and phase-change heat transfer.

PMID- 29214807
TI  - Self-Assembled Core-Shell CdTe/Poly(3-hexylthiophene) Nanoensembles as Novel
      Donor-Acceptor Light-Harvesting Systems.
AB  - The self-assembly of novel core-shell nanoensembles consisting of regioregular
      poly(3-hexylthiophene) nanoparticles (P3HTNPs) of 100 nm as core and
      semiconducting CdTe quantum dots (CdTeQDs) as shell with a thickness of a few
      tens of nanometers was accomplished by employing a reprecipitation approach. The
      structure, morphology, and composition of CdTeQDs/P3HTNPs nanoensembles were
      confirmed by high-resolution scanning transmission microscopy and dynamic light
      scattering studies. Intimate interface contact between the CdTeQDs shell and the
      P3HTNPs core leads to the stabilization of the CdTeQDs/P3HTNPs nanoensemble as
      probed by the steady-state absorption spectroscopy. Effective quenching of the
      characteristic photoluminescence of CdTeQDs at 555 nm, accompanied by
      simultaneous increase in emission of P3HTNPs at 660 and 720 nm, reveals
      photoinduced charge-transfer processes. Probing the redox properties of films of
      CdTeQDs/P3HTNPs further proves the formation of a stabilized core-shell system in
      the solid state. Photoelectrochemical assays on CdTeQDs/P3HTNPs films show a
      reversible on-off photoresponse at a bias voltage of +0.8 V with a 3 times
      increased photocurrent compared to CdTeQDs. The improved charge separation is
      directly related to the unique core-shell configuration, in which the outer
      CdTeQDs shell forces the P3HTNPs core to effectively act as electron acceptor.
      The creation of novel donor-acceptor core-shell hybrid materials via self
      assembly is transferable to other types of conjugated polymers and semiconducting
      nanoparticles. This work, therefore, opens new pathways for the design of
      improved optoelectronic devices.

PMID- 29214808
TI  - Investigation of Cytotoxic Activity of Mitoxantrone at the Individual Cell Level
      by Using Ionic-Liquid-Tag-Enhanced Mass Spectrometry.
AB  - A novel mitoxantrone conjugate was synthesized by coupling mitoxantrone with
      ionic liquid tags, and cytotoxic behavior of the designed conjugate was studied
      in normal and cancer cell lines. The synthesized mitoxantrone conjugate was oil
      at physiological temperatures and demonstrated high aqueous solubility.
      Sensitivity of electrospray ionization mass spectrometry (ESI-MS) to the
      mitoxantrone conjugate was improved by an order of magnitude, in comparison with
      original mitoxantrone dihydrochloride. The observed ESI-MS signals were shifted
      to a "clearer" lower-mass region of the spectrum, which allowed investigation of
      the drug at the level of individual cells. The ionic liquid tags proposed in the
      present work consist of an easily available imidazolium salt residue and show a
      number of key advantages from the points of view of drug conjugate synthesis,
      drug delivery and analytic detection.

PMID- 29214810
TI  - The Nation's Disaffected and Workplace Health Promotion.

PMID- 29214809
TI  - Trajectories of Cigarette Smoking From Teens to Young Adulthood: 2000 to 2013.
AB  - PURPOSE: To identify trajectories of smoking behaviors of a cohort of youth
      followed through young adulthood from 2000 to 2013. DESIGN: The Minnesota
      Adolescent Community Cohort study, a population-based cohort study. SETTING:
      Nationwide, originating in the Midwestern United States. PARTICIPANTS: Cohort of
      youth surveyed for 14 years beginning at ages 12 to 16 (N = 4241 at baseline; 59%
      recruitment rate). MEASURES: Main variable of interest was the number of days
      smoked in the past 30 days. Also included time-varying and time-invariant
      covariates. ANALYSIS: We utilized growth mixture modeling to group individuals
      into trajectories over time. RESULTS: We identified 5 distinct trajectories:
      nonsmokers (59.5%), early-onset regular smokers (14.2%), occasional smokers
      (11.5%), late-onset regular smokers (9.4%), and quitters (5.3%). Adjusted models
      showed that early- and late-onset regular smokers (compared to nonsmokers) had
      lower odds of attending or graduating from a 4-year college ( P < .05).
      Participants in all smoking classes compared to nonsmokers had greater odds of
      having more close friends who smoked ( P < .05). CONCLUSION: Our results show
      that individuals in their teens through young adulthood can be classified into 5
      smoking trajectories. More people in this age range remained abstainers than
      found in most previous studies; however, a sizable group was identified as
      regular smokers by the time they reached young adulthood. Interventions targeted
      at teens, including those that address social and environmental influences, are
      clearly still needed to prevent escalation of smoking as they move toward young
      adulthood.

PMID- 29214811
TI  - Rural-Urban Disparities in Obesity Prevalence Among Working Age Adults in the
      United States: Exploring the Mechanisms.
AB  - PURPOSE: Higher prevalence rates of overweight and obesity in rural America have
      been consistently reported, but sources of these disparities are not well known.
      This study presented patterns and mechanisms of these disparities among working
      age Americans. DESIGN: Cross-sectional study. SETTING: United States of America.
      PARTICIPANTS: The study included 10 302 participants of the 2003-2008 National
      Health and Nutrition Examination Survey (NHANES) who were 20 to 64 years old, not
      pregnant, and with a body mass index ranging from 18.5 to 60. MEASURES:
      Individual-level data were from NHANES including age, gender, race/ethnicity,
      immigrant status, education, and family income. The outcomes were prevalence of
      obesity and prevalence of overweight and obesity combined. Neighborhood data were
      constructed from the 2000 US Census providing tract-level information on family
      median income and built environmental features and from the 2006 ESRI ArcGIS 9.3
      Data DVD providing tract-level park location information. ANALYSIS: Geographic
      information system (GIS) methods were used to create a measure of spatial
      distance to local parks capturing park accessibility. Random intercept logistic
      and ordinal logit regression analyses were performed. FINDINGS: Multivariate
      regression results showed that the odds of obesity was higher in rural areas
      compared to urban areas (odds ratio = 1.358, P < .001) net of demographic
      controls and that this gap was largely attributable to individual educational
      attainment and neighborhood median household income and neighborhood built
      environmental features. After controlling for these hypothesized mediators, the
      elevated odds associated with rural residence was reduced by nearly 94% and
      rendered statistically insignificant. CONCLUSIONS: In this nationally
      representative cross-sectional sample, rural-urban obesity disparities were large
      and explained by rural-urban educational differences at the individual level and
      economic and built environmental differences at the neighborhood level.

PMID- 29214812
TI  - Prevalence and Implementation Practices of School Salad Bars Across Grade Levels.
AB  - PURPOSE: To assess the prevalence of school salad bars in Arizona and to describe
      common practices of salad bar use among school nutrition managers across grade
      level. DESIGN: Cross-sectional web-based surveys. PARTICIPANTS: School nutrition
      managers from elementary, middle, high, and K-12 schools (N = 648). MEASURES:
      Prevalence of salad bars; implementation practices such as years with salad bar,
      salad bar type, location, monitor, and reimbursement practices; and food-related
      components of salad bars including frequency of items, popular items, and sources
      of food. ANALYSIS: Descriptive analyses were conducted including Fisher exact
      test, analysis of variance, and the Kruskal-Wallis test comparing practices
      across grade level (elementary, middle, high, and K-12 schools). RESULTS:
      Overall, 61.1% of respondents had a salad bar; there were significant differences
      in the prevalence across grade level: elementary, middle, high, and K-12 schools
      had prevalence of 67.3%, 75.0%, 45.5%, and 51.1%, respectively ( P < .001). We
      observed significant differences in the implementation and food-related
      components of salad bars across grade levels including type, salad bar location,
      sources of food, and frequency of serving cut vegetables. CONCLUSION: This study
      provides insights on the prevalence of salad bars and is the first to report on
      implementation practices of school salad bars. These results may also guide the
      development of interventions for nutrition educators to use for the promotion
      fruit and vegetable consumption via school salad bars.

PMID- 29214813
TI  - Development, Implementation, and Evaluation of Active Lions: A Campaign to
      Promote Active Travel to a University Campus.
AB  - PURPOSE: To outline the development, implementation, and evaluation of a
      multistrategy intervention to promote active transportation, on a large
      university campus. DESIGN: Single group pilot study. SETTING: A large university
      in the Northeastern United States. PARTICIPANTS: University students (n = 563),
      faculty and staff (employees, n = 999) were included in the study. INTERVENTION:
      The Active Lions campaign aimed to increase active transportation to campus for
      all students and employees. The campaign targeted active transport participation
      through the development of a smartphone application and the implementation of
      supporting social marketing and social media components. MEASURES: Component
      specific measures included app user statistics, social media engagement, and
      reach of social marketing strategies. Overall evaluation included cross-sectional
      online surveys preintervention and postintervention of student and employee
      travel patterns and campaign awareness. ANALYSIS: Number of active trips to
      campus were summed, and the percentage of trips as active was calculated. T tests
      compared the differences in outcomes from preintervention to postintervention.
      RESULTS: Students had a higher percentage of active trips postintervention
      (64.2%) than preintervention (49.2%; t = 3.32, P = .001), although there were no
      differences for employees (7.9% and 8.91%). Greater awareness of Active Lions was
      associated with greater active travel. CONCLUSION: This multistrategy approach to
      increase active transportation on a college campus provided insight on the
      process of developing and implementing a campaign with the potential for
      impacting health behaviors among campus members.

PMID- 29214814
TI  - Barriers to Engagement in a Workplace Weight Management Program: A Qualitative
      Study.
AB  - PURPOSE: To investigate (1) why some participants in a workplace weight
      management program were more engaged in the program, (2) specific barriers and
      facilitators for engagement and weight loss, and (3) suggest how workplaces may
      better engage employees in these programs to improve their effectiveness. DESIGN:
      Qualitative study (8 focus groups). SETTING: A large academic university and
      medical system. PARTICIPANTS: Twenty-six (5%) of the 550 employees who
      participated in a weight management program as part of the Steps to Health study.
      MEASURES: A trained moderator guided the audio-recorded focus groups. ANALYSIS:
      Transcripts were analyzed using the directed content analysis approach. RESULTS:
      Participants faced numerous barriers to engagement in workplace weight management
      programs, both within and outside the workplace. Participants viewed the coaches
      positively and reported that the coaches had a strong influence on their
      engagement in the program. Participants suggested increased frequency and variety
      of contact by coaches, on-site group exercise classes, and tailored educational
      materials. CONCLUSION: Workplace weight management programs may be improved by
      being more flexible around participants' schedules and changing needs, by
      increasing access to affordable, convenient exercise facilities, and by
      implementing institutional changes that encourage healthy eating and physical
      activity during the workday. Employers should measure program engagement and
      solicit participant feedback to ensure that the programs are appropriate and
      delivered in an optimal manner.

PMID- 29214815
TI  - Using the Theory of Planned Behavior to Guide Focus Group Development of Messages
      Aimed at Increasing Compliance With a Tobacco-Free Policy.
AB  - PURPOSE: This study details the persuasive message development for a theory-based
      campaign designed to increase compliance with a university's tobacco-free policy.
      APPROACH: The theory of planned behavior (TPB) guided message design and
      evaluation for focus group-tested messages that were adapted to the context of
      complying with a tobacco-free policy. SETTING: The study was conducted at a
      university located in the tobacco belt. PARTICIPANTS: Undergraduate focus group
      participants (n = 65) were mostly male (69%), white (82%), and freshman (62%) who
      smoked at least 1 cigarette in the last 30 days; on-campus smoking percentages
      were never/rare (60%), occasionally (23%), and often/frequently (16%). METHOD:
      Data analysis used a theoretical thematic approach to identify how the TPB
      constructs related to perceptions of message effectiveness. RESULTS: Participants
      responded favorably to attitudinal strategies about health, respect, and
      university figures; they rejected approaches they considered juvenile and
      offensive. They also discussed the impact of noncompliance and avoiding
      overgeneralized statements for addressing subjective norms, suggesting shortening
      text, adjusting picture location, and emphasizing the importance of compliance to
      increase perceptions of behavioral control. CONCLUSION: Applying theory to
      preexisting messages is challenging. The design approach in this study is an
      evidence-based strategy that can be used as a universal process for message
      adaptation. Results offer health promotion suggestions for designing messages
      aimed at improving undergraduate smokers' willingness to comply with tobacco-free
      campus policies.

PMID- 29214816
TI  - Left ventricular free wall rupture after surgery for ventricular septal rupture.
AB  - A 67-year-old man presented with late left ventricular free wall rupture 1 month
      after an extended sandwich technique through a right ventricular incision for
      ventricular septal rupture following an inferoposterior acute myocardial
      infarction. We found that residual infarcted myocardium had led to left
      ventricular aneurysm formation. A pericardial patch on the left ventricular side
      at the initial operation should have been secured further from the septal defect
      using a larger needle. A patch on the left ventricular side is important for
      complete exclusion of a free wall infarction and for decreasing the stress on the
      suture line securing the patch.

PMID- 29214817
TI  - Do Monetary Incentives Increase Fitness Center Utilization? It Depends.
AB  - PURPOSE: To examine the effects of an employer-based monetary incentive program
      on membership termination and usage at a fitness center. DESIGN: Retrospective
      nested case-control study examining the relationship between participation in an
      incentive program, visits to the fitness center, and membership termination at 1
      year. SETTING: University-based fitness center. PARTICIPANTS: Members (N = 1122)
      of a university-based fitness center. INTERVENTION: Members were offered either a
      US$25 incentive for each month they visited the fitness center at least 10 times
      or no incentive. MEASURES: Data were extracted from the membership database and
      included membership termination at 1 year (yes, no), length of membership (days),
      participation in the incentive program (yes, no), and visits to the fitness
      center per month. ANALYSIS: Cox proportional hazards model. RESULTS: Members in
      the incentive program visited the fitness center on average more times per month
      (5.3 vs 4.3; P < .0001) but were significantly more likely to terminate
      memberships at 1 year compared to members who did not receive the incentive (38%
      vs 31%; P = .013). After controlling for relevant covariates, members who
      received the incentive had a 24% greater hazard of terminating their memberships
      compared to members who did not receive the incentive (hazard ratio [HR] = 1.24;
      P = .041). After controlling for the number of visits per month, the incentive
      program was no longer significantly related to membership termination (HR = 1.21;
      P = .07). CONCLUSION: Being in a monetary incentive program to attend a fitness
      center may be initially associated with a greater fitness center utilization but
      may not be associated with a reduced risk of membership termination.

PMID- 29214818
TI  - Colorectal Cancer Screening Completion Among Individuals With and Without Mental
      Illnesses: A Comparison of 2 Screening Methods.
AB  - PURPOSE: Cancer mortality is worse among people with psychiatric disorders. The
      purpose of this study was to compare facilitators and rates of colorectal cancer
      (CRC) screening between people with and without mental illnesses. DESIGN: We
      conducted a secondary analysis using data from a general population cohort study
      (N = 92 445) that assessed effects of 2 types of CRC screening test kits-guaiac
      fecal occult blood testing (gFOBT) and fecal immunochemical testing (FIT)-on CRC
      screening completion. SETTING: The setting was a health system that served
      approximately 485 000 members in urban and suburban Oregon and Washington.
      PARTICIPANTS: Participants were health system members, categorized by mental
      illness diagnosis (psychotic disorders, non-psychotic unipolar depression, and no
      mental illness), who were age-eligible, at average risk of CRC, and were at least
      366 days past their last gFOBT with no evidence of other CRC screening. MEASURES:
      The outcome was time until completion of CRC screening. ANALYSIS: We used Cox
      proportional hazard models. RESULTS: FIT reduced CRC screening barriers for all
      the groups. Compared to people without mental illness diagnoses, those with
      psychotic disorders were equally likely to screen using FIT (hazard ratio [HR] =
      .95, p = .679) and those with depression were more likely (HR = 1.17, p = .006).
      CONCLUSIONS: FIT can improve CRC screening rates among people with mental
      illnesses, particularly depression.

PMID- 29214819
TI  - The Influence of Weight Status Duration on Weight Perception Accuracy.
AB  - PURPOSE: To examine the association between weight status duration and weight
      perception accuracy. DESIGN: Retrospective study. SETTING: National Health and
      Nutrition Examination Survey 2003 to 2006. SAMPLE: A total of 4029 adults aged 20
      years or older. MEASURES: To assess weight status duration, participants' past
      (10 years ago) and present body mass indexes were used to create 4 groups: normal
      weight in the past and present (group 1), normal weight in the past but
      overweight/obese in the present (group 2), overweight/obese in the present but
      not in the past (group 3), and overweight/obese in the past and present (group
      4). We classified individuals as having an accurate/inaccurate weight perception
      based on present body mass index and whether they considered themselves as
      overweight, underweight, or about the right weight. ANALYSIS: Logistic
      regression. RESULTS: Our findings suggest that participants who were
      overweight/obese in the past, present, or during both time periods had increased
      odds of possessing an inaccurate weight perception. Furthermore, being normal
      weight in the past but obese in the present increased the odds of having an
      inaccurate weight perception nearly 10-fold and almost 5-fold for those obese in
      both the past and present. CONCLUSION: Studies such as this can aid clinicians in
      identifying individuals who may have increased odds of inaccurately identifying
      their weight status, thereby providing additional opportunities to facilitate
      weight loss.

PMID- 29214820
TI  - Weight Management Behaviors Among Mexican American Youth: Cross-Sectional
      Variation by Timing of Growth and Maturation.
AB  - PURPOSE: To assess the association between growth and maturation with weight
      management behaviors (WMBs) among Mexican American youth. DESIGN: A cross
      sectional design was used to measure timing of growth and maturation as well as
      WMBs. SAMPLE: Students were recruited through physical education classes in south
      Texas schools. The sample included 623 participants (52.3% female; 49.8% with
      weight >=85th percentile) in grades 4 through 12. Students in middle school were
      purposely oversampled to examine questions around timing of growth and
      maturation. MEASURES: Growth was measured as maturity offset, an estimate of age
      at peak height velocity (PHV). Maturity offset is derived from chronological age,
      height, and sitting height measurements. Participants were classified as pre-PHV
      or post-PHV. Girls also were categorized as premenarche or early, average, or
      late maturing based on age at menarche. Weight was measured to calculate body
      mass index (BMI) percentile. Weight management behavior and timing of menarche
      were self-reported via a survey. ANALYSIS: Descriptive characteristics were
      calculated for boys and girls separately. chi2 Tests of proportion were used to
      test WMB by BMI percentile. Logistic regression analyses were conducted to
      examine the likelihood of engaging in WMB by maturity offset and, for girls,
      timing of menarche. RESULTS: Students with weight >=85th percentile were more
      likely to describe themselves as overweight and report trying to lose weight
      through exercise or calorie restriction ( P < .0001). A 1-year increase in
      maturity offset was associated with youth being 31% more likely to perceive
      themselves as overweight but less likely to report calorie restriction (odds
      ratio [OR] = 0.87). Average maturing girls were more likely than premenarcheal
      girls to exercise, restrict calories, or fast to lose weight (OR = 3.27, 2.11,
      and 3.27, respectively). CONCLUSION: Mexican American youth are engaging in WMB,
      even when their weight status is <85th percentile. The appropriateness of weight
      management counseling may need to consider a child's stage of growth.

PMID- 29214821
TI  - "At First I Couldn't Catch My Breath": Process and Strategies for Managing
      Chronic Obstructive Pulmonary Disease.
AB  - In this article, we describe the process and strategies that study participants
      living with chronic obstructive pulmonary disease in central Canada utilized to
      manage and live well with their illness and its associated symptoms. Drawing on
      interpretive phenomenology, we interviewed eight participants three times,
      followed by a member checking focus group and individual interviews. We analyzed
      interview transcripts using detailed line by line analysis. Our findings suggest
      participants engaged in a challenging process of recognizing that changes had
      occurred and then coming to terms with these changes by acknowledging the
      severity of their condition and the resulting limitations. Then, participants
      drew upon several strategies to minimize feelings of breathlessness, including
      taking care of themselves, managing risk, and altering behavior. Participants
      acknowledged the challenges inherent to this process, yet described how they were
      able to live well with chronic obstructive pulmonary disease through their
      adaptations.

PMID- 29214822
TI  - Meeting Sleep Guidelines Is Associated With Better Health-Related Quality of Life
      and Reduced Premature All-Cause Mortality Risk.
AB  - PURPOSE: To examine whether meeting sleep guidelines (7-9 hours/night) is
      associated with better health-related quality of life (HRQOL) and reduced all
      cause mortality risk. DESIGN: Prospective cohort study. SETTING: 2005 to 2010
      National Health and Nutrition Examination Survey. PARTICIPANTS: A total of 13 423
      adults. MEASURES: Sleep duration and HRQOL were assessed from self-report;
      covariates assessed via survey, examination, and laboratory data; and mortality
      assessed through 2011 via matching from the National Death Index. ANALYSIS: Cox
      proportional hazard regression and ordinal logistic regression. RESULTS: After
      adjusting for age, gender, race-ethnicity, body mass index, education, smoking,
      white blood cell level, iron level, red blood cell distribution width, mean
      platelet volume, blood pressure, diabetes, coronary artery disease, physical
      activity, and depression, those meeting sleep guidelines had an 19% reduced risk
      of premature all-cause mortality (hazard ratio = 0.81; 95% confidence interval
      [CI]: 0.67-0.99; P = .04). After adjustments, those meeting sleep guidelines had
      better HRQOL (beta = -0.30; 95% CI: -0.38 to -0.21; P < .001). Results for the
      ordinal regression and Cox proportional analyses were similar in unadjusted and
      minimally adjusted models. CONCLUSION: Obtaining optimal levels of sleep is
      associated with better HRQOL and reduced premature mortality risk, independent of
      demographic, behavioral, and biological conditions. These findings underscore the
      importance of achieving optimal levels of sleep.

PMID- 29214824
TI  - Surgical challenge in situs inversus with dextrocardia and Lutembacher syndrome.
AB  - Situs inversus with dextrocardia and Lutembacher syndrome is a rare cardiac
      anomaly. It is associated with other complex cardiac anomalies and anatomical
      defects. A 30-year-old woman with this condition underwent mitral valve
      replacement and closure of a secundum atrial septal defect. We describe the
      surgical approach, position of the surgeon, and bicaval cannulation technique for
      this anatomical aberration.

PMID- 29214825
TI  - Effects of Pride and Regret on Geriatric Depression: A Cross-Cultural Study With
      Mixed-Methods Approaches.
AB  - Pride and regret are self-conscious emotions that develop later in life and
      become a source of emotional struggle. This cross-cultural study examined the
      effect of the content and intensity of self-conscious emotions on Geriatric
      Depression Scale (GDS) scores. Among a convenience sample of 234 older adults
      (130 in the United States and 104 in South Korea), the contents and intensities
      of both life regrets and pride were examined. Although a greater variety of
      regrets was cited by Americans, overall Korean respondents reported higher
      intensity of regret. Regrets that were related to leisure and addiction among
      Americans and health and career among Koreans were predictors of the GDS scores.
      Pride in leisure activities for Americans and altruism among Koreans could
      alleviate depression. While regrets and pride explained a small amount of the
      variance in the GDS scores, current life stressors greatly contributed to
      geriatric depression.

PMID- 29214826
TI  - Effects of a Sedentary Intervention on Cognitive Function.
AB  - PURPOSE: To examine the effects of a free-living, sedentary-inducing intervention
      on cognitive function. DESIGN: Randomized controlled, parallel group
      intervention. SETTING: University campus. PARTICIPANTS: Thirty-three young adults
      (n = 23 intervention; n = 10 control). MEASURES: The intervention group was asked
      to eliminate all exercise and minimize steps to <=5000 steps/day for 1 week,
      whereas the control group was asked to continue normal physical activity (PA)
      levels for 1 week. Both groups completed a series of 8 cognitive function
      assessments (assessing multiple parameters of cognition) preintervention and
      immediately postintervention. The intervention group was asked to resume normal
      PA levels for 1 week postintervention and completed the cognitive assessments for
      a third time at 2 weeks postintervention. ANALYSIS: Split-plot repeated-measures
      analysis of variance. RESULTS: The results of our statistical analyses showed
      that the group * time interaction effect was not significant ( P > .05) for any
      of the evaluated cognitive parameters. CONCLUSION: These findings demonstrate the
      need for future experimental investigations of sedentary behavior to better
      understand its effects on cognitive function. However, although previous work has
      demonstrated favorable effects of acute and chronic PA on cognitive function, our
      findings suggest that a 1-week period of reduced PA does not detrimentally affect
      cognitive function, which may have encouraging implications for individuals going
      through a temporary relapse in PA.

PMID- 29214827
TI  - The Impact of Protective Behavioral Strategy Use Frequency on Blood Alcohol
      Concentrations Among Student Drinkers Nationwide.
AB  - PURPOSE: This study assessed whether college student (1) protective behavioral
      strategy (PBS) use differed between those who reached legal intoxication during
      their most recent drinking episode compared to those who did not reach the legal
      blood alcohol concentration (BAC) threshold, and (2) frequency of PBS use could
      explain the variance associated with BAC during the most recent drinking episode,
      above and beyond one's sex, age, and involvement in the Greek system. DESIGN:
      Secondary data analysis of the American College of Health Association's National
      College Health Assessment. SETTING: Forty-four distinct campuses were included.
      PARTICIPANTS: A total of 21479 college students were included. MEASURES: BAC and
      PBS were measured. ANALYSIS: The data were analyzed by conducting both
      independent samples t-tests and a multiple regression model. Effect sizes are
      reported. RESULTS: Participants who reached legal intoxication used PBS less
      frequently ( P < .001; d = 0.80). Frequency of PBS use had the strongest unique
      contribution to the regression model (beta = -.315, P < .001), such that
      participants with higher BAC reported less frequent use of PBS. CONCLUSION:
      Interventions should seek to develop strategies that encourage college student
      use of PBS prior to, and during, drinking episodes. More frequent use of PBS can
      reduce intoxication as well as occurrence of alcohol-associated consequences.

PMID- 29214828
TI  - Dose-Response Association Between Physical Activity and Cognitive Function in a
      National Sample of Older Adults.
AB  - PURPOSE: Previous research demonstrates a favorable effect of physical activity
      on cognitive function among older adults. The potential dose-response
      relationship between physical activity and cognitive function in this population
      is less understood, which was the purpose of this study. SETTING: Data from the
      1999 to 2002 National Health and Nutrition Examination Survey were employed.
      PARTICIPANTS: A total of 2157 older adults aged 60 to 85 years. MEASURES:
      Cognitive function was assessed from the Digit Symbol Substitution Test. Moderate
      to-vigorous physical activity (MVPA), expressed as metabolic equivalent of task
      (MET)-min-month (MET-min-month = days * duration * MET level), was assessed via
      self-report, with 5 MVPA categories evaluated: (1) <2000 MVPA MET-min-month, (2)
      2000 to 3999 MVPA MET-min-month, (3) 4000 to 5999 MVPA MET-min-month, (4) 6000 to
      7999 MVPA MET-min-month, and (5) 8000+ MVPA MET-min-month. ANALYSIS: Weighted
      multivariable linear regression. RESULTS: An inverted U-shaped relationship was
      observed. Consistent across several adjusted models, those who engaged in 6000 to
      7999 MVPA MET-min-month had the highest cognitive function score. CONCLUSION: The
      results suggest an optimal amount of physical activity to prevent the cognitive
      decline associated with aging.

PMID- 29214829
TI  - Promoting Stair Climbing in a Worksite and Public Setting: Are Footprints Enough?
AB  - PURPOSE: To evaluate the impact of footprints on stair climbing in different
      settings. DESIGN: Interrupted time-series design. SETTING: A company
      (stair/elevator choice) and a mall (stair/escalator choice). PARTICIPANTS:
      Employees (n = 5676) and visitors of the mall (n = 12 623). INTERVENTION: An
      intervention comprising 3 consecutive phases was implemented-(1) footprints
      leading to the stairs were stuck on the floor, (2) a health message referring to
      the footprints was introduced, and (3) passersby were congratulated for their
      increased stair use. MEASURES: Stair climbing was observed before (ie, baseline),
      during, and 6 to 13 weeks after (ie, follow-up) the intervention. ANALYSIS:
      Proportions of stair climbers were compared using chi2 analyses. RESULTS: The
      footprints resulted in a closely significant increase in stair climbing in the
      company (from 27.7% at baseline to 31.2% in phase 1). However, they did not
      produce any effect in the mall. Introducing a health message yielded an
      additional 12.4% increase in stair climbing in the company and a significant
      11.4% increase in the mall (22.3% in phase 2). Congratulating people did not
      further increase stair climbing. At follow-up, the proportions of stair climbers
      dropped but still exceeded baseline. CONCLUSION: Footprints tend to increase
      stair climbing in a worksite setting with a stair/escalator choice but not in a
      public setting with a stair/elevator choice. Adding a meaningful message seems
      essential to obtain stronger and longer term effects.

PMID- 29214830
TI  - Religiosity, the Practices of Religions, and the Perception of Older People Among
      Muslims and Buddhists in Thailand.
AB  - We examined the effects of religiosity and the practices of religions among the
      Buddhists and Muslims aged 20 to 79 in Thailand on maintaining positive attitudes
      toward older people. Factor and multiple regression analyses are applied, using
      data from the 2011 National Survey on Conditions of Society and Culture. The
      measures of perception of older people are Social Value and Personal Value.
      Religiosity is measured by the self-assessment of religious strictness and one's
      own practices according to the religious principles. Among Buddhists, the
      practices are measured by the frequency of praying, Takbat, Pancha Sila, and
      meditation. For Muslims, the practices are measured by the frequency of doing
      Salat, observing Saum, and giving Zakat. We found that religiosity and some
      practices of religions have positive effects on the perception of the value of
      older people. In addition, social policy for a smooth transition to an aging
      society should be considered alongside this religious mechanism.

PMID- 29214831
TI  - Exploring Individual, Family, and Extrafamilial Factors Associated With
      Depression Among Elderly Residents of Care Settings.
AB  - This study investigated simultaneously the associations among individual, family,
      and extrafamilial factors and depression among elderly residents of care settings
      in Taiwan. The data for this study were obtained from the Vulnerability and
      Social Exclusion among Different Groups of Disadvantaged Elderly in an Aging
      Society: Phenomena and Strategies (1/2) project, which was conducted in Taipei
      City and Taipei County in 2007. We applied multiple regression procedures to a
      sample of 327 residents of care settings (48.3% women) who were mild physical
      impairment or physically independent and cognitively clear for determining
      factors associated with depression and their cumulative effects. We discovered
      that 24.5% of the residents were depressed. Physical mobility, number of chronic
      diseases, and self-assessed health status were significantly associated factors
      in all models. In the final model, we determined that one third of extrafamilial
      factors were significantly associated with depression, after controlling for all
      other variables. In addition, we observed an overall trend of increased mean
      scores of depression with an increase in the number of risk factors. The results
      imply that interventions aimed at preventing depression in elderly persons living
      in care settings, particularly persons with multiple risk conditions such as
      impaired physical mobility and medical comorbidities, should be designed to
      include extrafamilial elements. Establishing strong connections between elderly
      care setting residents and the institutional and neighborhood environments can
      help prevent depression.

PMID- 29214832
TI  - Tailored Educational Approaches for Consumer Health: A Model to Address Health
      Promotion in an Era of Personalized Medicine.
AB  - PURPOSE: To develop a model, based on market segmentation, to improve the quality
      and efficiency of health promotion materials and programs. DESIGN: Market
      segmentation to create segments (groups) based on a cross-sectional questionnaire
      measuring individual characteristics and preferences for health information.
      Educational and delivery recommendations developed for each group. SETTING:
      General population of adults in Virginia. PARTICIPANTS: Random sample of 1201
      Virginia residents. Respondents are representative of the general population with
      the exception of older age. MEASURES: Multiple factors known to impact health
      promotion including health status, health system utilization, health literacy,
      Internet use, learning styles, and preferences. ANALYSIS: Cluster analysis and
      discriminate analysis to create and validate segments. Common sized means to
      compare factors across segments. RESULTS: Developed educational and delivery
      recommendations matched to the 8 distinct segments. For example, the "health
      challenged and hard to reach" are older, lower literacy, and not likely to seek
      out health information. Their educational and delivery recommendations include a
      sixth-grade reading level, delivery through a provider, and using a "push"
      strategy. CONCLUSION: This model addresses a need to improve the efficiency and
      quality of health promotion efforts in an era of personalized medicine. It
      demonstrates that there are distinct groups with clearly defined educational and
      delivery recommendations. Health promotion professionals can consider Tailored
      Educational Approaches for Consumer Health to develop and deliver tailored
      materials to encourage behavior change.

PMID- 29214833
TI  - Living with functionally univentricular heart: beating the odds?
AB  - An unoperated 45-year-old man with double-inlet single left ventricle, transposed
      great arteries, ventricular septal defect, and pulmonary stenosis presented with
      mitral and pulmonary valvular vegetations unresponsive to antibiotic therapy. The
      initial diagnosis was made with echocardiography, and the morphology was
      delineated with computed tomography and magnetic resonance imaging. The patient
      underwent mitral valve replacement with a mechanical valve and pulmonary valve
      vegetectomy. He recovered well and he is currently well two years after the
      operation.

PMID- 29214834
TI  - Source and Size of Social Support Network on Sedentary Behavior Among Older
      Adults.
AB  - PURPOSE: To examine the association of source of social support and size of
      social support network on sedentary behavior among older adults. DESIGN: Cross
      sectional. SETTING: National Health and Nutrition Examination Survey 2003 to
      2006. PARTICIPANTS: 2519 older adults (60+ years). MEASURES: Sedentary behavior
      was assessed via accelerometry over a 7-day period. Social support was assessed
      via self-report. Sources evaluated include spouse, son, daughter, sibling,
      neighbor, church member, and friend. Regarding size of social network,
      participants were asked, "In general, how many close friends do you have?"
      ANALYSIS: Multivariable linear regression. RESULTS: After adjustment, there was
      no evidence of an association between the size of social support network and
      sedentary behavior. With regard to specific sources of social support, spousal
      social support was associated with less sedentary behavior (beta = -11.6; 95%
      confidence interval: -20.7 to -2.5), with evidence to suggest that this was only
      true for men. Further, an inverse association was observed between household size
      and sedentary behavior, with those having a greater number of individuals in the
      house having lower levels of sedentary behavior. These associations occurred
      independent of moderate-to-vigorous physical activity, age, gender, race
      ethnicity, measured body mass index, total cholesterol, self-reported smoking
      status, and physician diagnosis of congestive heart failure, coronary artery
      disease, stroke, cancer, hypertension, or diabetes. CONCLUSION: Spouse-specific
      emotion-related social support (particularly for men) and household size were
      associated with less sedentary behavior.

PMID- 29214835
TI  - Tobacco Smoke Exposure and Health-Care Utilization Among Children in the United
      States.
AB  - PURPOSE: The purpose of this study was to assess patterns of health-care
      utilization among children who potentially had tobacco smoke exposure (TSE)
      compared to those who were not exposed. DESIGN: A secondary data analysis of the
      2011 to 2012 National Survey on Children's Health was performed. SETTING:
      Households nationwide were selected. PARTICIPANTS: A total of 95 677 children
      aged 0 to 17 years. MEASURES: Sociodemographic characteristics, TSE status, and
      health-care visits were measured. ANALYSIS: Multivariable logistic regression
      models were performed. RESULTS: A total of 24.1% of children lived with smokers.
      Approximately 5% had home TSE. Participants who lived with a smoker were
      significantly more likely to have had a medical care visit (odds ratio [OR] =
      1.22, confidence interval [CI] = 1.21-1.22) and were more likely to seek sick
      care or health advice at an emergency department (OR = 1.23, CI = 1.23-1.24) but
      were less likely to have had a dental care visit (OR = 0.82, CI = 0.82-0.83) than
      those who did not live with a smoker. Similar findings were found among
      participants who had home TSE. CONCLUSION: TSE is a risk factor for increased use
      of pediatric medical care. Based on the high number of children who potentially
      had TSE and received sick care or health advice at an emergency emergency
      department, this setting may be a venue to deliver health messages to caregivers.

PMID- 29214836
TI  - "No High Like a Brownie High": A Content Analysis of Edible Marijuana Tweets.
AB  - PURPOSE: To investigate tweets about marijuana edibles for surveillance into the
      content of edibles-related tweets among individuals socially networking about
      this topic on Twitter. DESIGN: Cross-sectional analysis of tweets containing
      edible marijuana-related key words during 1 month. SETTING: Twitter.
      PARTICIPANTS: Tweets sent during January 1 to 31, 2015. METHODS: A random sample
      of 5000 tweets containing edibles-related key words was coded for sentiment
      (positive, negative, and neutral) by crowdsourced workers. Tweets normalizing or
      promoting edibles use were further analyzed, and demographic characteristics of
      the Twitter handles sending these tweets were inferred. RESULTS: Of the 5000
      tweets, 4166 (83%) were about marijuana edibles, and of those 75% (3134 of 4166)
      normalized or encouraged edibles use. Nearly half (48%, 1509 of 3134) of the
      tweets normalizing edibles mentioned wanting or planning to consume, currently
      consuming, or recently consuming edibles, and 12% (378 of 3134) described the
      intense or long-lasting effects following use. Individuals whose tweets
      promoted/encouraged edibles use were more likely to be young (between 17 and 24
      years old) and of a racial/ethnic minority (52% black; 12% Hispanic) when
      compared to the Twitter average. CONCLUSION: Tweets that normalize edibles use
      have the potential to increase their popularity. The prevalence of tweets about
      edibles' intense high could have implications for tailoring prevention messages
      that could be important for youth and young adult minorities who were inferred to
      be disproportionately socially networking about edibles on Twitter.

PMID- 29214837
TI  - Prediction of Physical Activity Level Using Processes of Change From the
      Transtheoretical Model: Experiential, Behavioral, or an Interaction Effect?
AB  - PURPOSE: The purpose of the present study was to compare prediction of physical
      activity (PA) by experiential or behavioral processes of change (POCs) or an
      interaction between both types of processes. DESIGN: A cross-sectional study.
      SETTING: This study was conducted using an online questionnaire. PARTICIPANTS: A
      total of 394 participants (244 women, 150 men), with a mean age of 35.12 +/-
      12.04 years and a mean body mass index of 22.97 +/- 4.25 kg/m2 were included.
      MEASURES: Participants completed the Processes of Change, Stages of Change
      questionnaires, and the International Physical Activity Questionnaire to evaluate
      self-reported PA level (total, vigorous, and moderate PA). ANALYSIS: Hierarchical
      multiple regression models were used to test the prediction of PA level. RESULTS:
      For both total PA (beta = .261; P < .001) and vigorous PA (beta = .297; P <
      .001), only behavioral POCs were a significant predictor. Regarding moderate PA,
      only the interaction between experiential and behavioral POCs was a significant
      predictor (beta = .123; P = .017). CONCLUSION: Our results provide confirmation
      that behavioral processes are most prominent in PA behavior. Nevertheless, it is
      of interest to note that the interaction between experiential and behavioral POCs
      was the only element predicting moderate PA level. Experiential processes were
      not associated with PA level.

PMID- 29214838
TI  - Sources and Number of Coupons for Cigarettes and Snus Received by a Cohort of
      Young Adults.
AB  - PURPOSE: To examine the sources of tobacco coupons and their influence on
      susceptibility to snus use. DESIGN: Cohort study. SETTING: Minnesota Adolescent
      Community Cohort Study. SUBJECTS: A population-based sample of US Midwest young
      adults in 2011 to 2012 and 2012 to 2013 (aged 22-28; n = 2384). MEASURES:
      Exposure to coupons for various tobacco products through various sources in the
      past 6 months, susceptibility to snus use. ANALYSIS: Multiple logistic
      regressions. RESULTS: During the 6 months prior to 2012 to 2013 survey, 11% of
      the sample received coupons for cigarettes, 5% received coupons for snus, 3%
      received coupons for other smokeless tobacco products, and <1% received coupons
      for little cigars. Direct mail was the most commonly cited source of cigarette
      and snus coupons. Tobacco product packaging provided the highest number of
      tobacco coupons for current and former smokers. Participants without a 4-year
      college education (compared to those who had a 4-year college education) were
      more likely to have received coupons for cigarettes and snus and received more
      coupons for both products ( P < .05). Racial/ethnic minority young adults (vs non
      Hispanic white) received more cigarette and snus coupons ( P < .05). Receiving
      snus coupons was positively associated with susceptibility to snus use ( P <
      .05). CONCLUSION: Tobacco companies are successful in reaching young adults using
      coupons for various tobacco products. Snus coupons may influence snus use,
      similar to how cigarette coupons influence smoking.

PMID- 29214839
TI  - Understanding West Africa's Ebola epidemic.

PMID- 29214840
TI  - Bifactor Models of Attention Deficit/Hyperactivity Symptomatology in Adolescents:
      Criterion Validity and Implications for Clinical Practice.
AB  - This study evaluated the fit and criterion validity of a bifactor model for 18
      DSM-IV attention deficit/hyperactivity disorder (ADHD) symptoms, along with nine
      supplementary symptoms that represented the manifestation of inattention and
      hyperactivity-impulsivity in adolescence and early adulthood. Participants
      included N = 172 adolescents who were diagnosed with combined type ADHD and who
      were enrolled in a treatment study. A bifactor model provided reasonably good fit
      to combined parent- and teacher-reported DSM symptoms and supplemental items at
      baseline prior to treatment. Across models, the general factor was characterized
      by high reliability (omega = .93, .95), while specific inattentive and
      hyperactive-impulsive factors were characterized by poor reliability (omega = .30
      .50). With respect to criterion validity, the general ADHD and specific
      inattentive factors were uniquely associated with home and school impairment ( R2
      = .13-.29) but not adolescent risk-tasking behavior. Results are discussed with
      respect to the ways in which bifactor models of ADHD inform the diagnostic
      criteria for ADHD.

PMID- 29214841
TI  - Effect of Area-Level Deprivation on Cancer Survival Time: A Register-Based Follow
      up Study of 145 585 Korean Subjects.
AB  - Our goal is to evaluate the strengths of the associations between area-level
      deprivation and survival time for a variety of cancers. A total of 145 585
      subjects were diagnosed with various cancers in Busan, Korea, and an area-level
      deprivation index constructed from several important socioeconomic variables. A
      multilevel Cox model was used in the analysis to investigate the effects of
      multiple risk factors. After adjusting for gender and age, an increased area
      level deprivation index was found to be significantly associated with a higher
      hazard rate for major cancers. Estimated hazard ratios (95% confidence interval)
      were 1.08 (1.06, 1.11), 1.15 (1.13, 1.18), and 1.22 (1.18, 1.25) for the second,
      third, and fourth quartiles of deprivation index groups, respectively, when
      compared with the least deprived group. When compared with the least deprived
      group, the more deprived group showed significant decrease in survival time for
      major cancers. This finding highlights the importance of preventive and care
      services incorporating socioeconomic characteristics of areas.

PMID- 29214842
TI  - Trastuzumab emtansine: determining its role in management of HER2+ breast cancer.
AB  - Trastuzumab emtansine is an antibody-drug conjugate comprised of the anti-HER2
      monoclonal antibody trastuzumab linked to DM1 (emtansine), a potent cytotoxic
      maytansinoid derivative, by a stable linker. This structure results in improved
      tumor-directed cytotoxicity in HER2+ breast cancer with reduced systemic
      toxicities, particularly the cardiac toxicities associated with single agent
      trastuzumab. Phase III trials have demonstrated improved progression-free and
      overall survival in heavily pretreated patients with advanced HER2+ breast
      cancer, with an acceptable toxicity profile. However, its role in first-line
      treatment is less clear. Ongoing studies continue to evaluate its role in
      neoadjuvant and adjuvant management of HER2+ breast cancer.

PMID- 29214843
TI  - Weaving social reality around the grandparent/great-grandparent with dementia to
      maintain relational presence: A verbal and non-verbal dementia interactions
      model.
AB  - We proposed a dementia interactions model based on analyses of five focus groups
      with grandchildren of grandparents with dementia. Interactions with their
      grandparent with dementia motivate grandchildren to maintain connection with a
      grandparent who is relationally present. To do so, they weave a social reality
      around the grandparent. To help the grandparent remain connected, grandchildren
      engage in scripts and routines and employ three intertwined psychological
      processes: perspective taking, vigilance, and knowledge about the grandparent's
      preferences, personality, state of mind, and context. Grandchildren use four
      relationship anchors to help the grandparent remain relationally present: family
      members, meaningful sensory objects and activities, physical space/context, and
      themselves. Implications for improving social interactions with close others with
      dementia are discussed.

PMID- 29214844
TI  - Barriers to Quitting Smoking Among Young Adults: The Role of Socioeconomic
      Status.
AB  - PURPOSE: The aims of this analysis were to explore how self-reported barriers to
      quitting vary by socioeconomic status (SES) among young-adult smokers and to
      assess their relationship to quitting. DESIGN: This analysis uses 2 waves of
      telephone-survey data from the Minnesota Adolescent Community Cohort study.
      SETTING: Midwestern United States. PARTICIPANTS: Participants (n = 419) were
      smokers aged 17 to 24 years. MEASURES: Socioeconomic status was estimated using
      the highest level of education completed by the participants' parents.
      Demographics, smoking behavior, and perceived barriers to quitting were collected
      via survey questions. ANALYSIS: Differences in barriers by SES were assessed
      using prevalence ratios (PRs). Relative risks were calculated to assess the
      association between barriers and quitting status 1 year later, testing for effect
      modification by SES. RESULTS: Compared to the high SES group (n = 314), the low
      SES group (n = 105) was more likely to report several barriers to quitting;
      however, only the risk of gaining weight was significantly more common (PR: 1.38
      [1.05-1.83]). There were no significant associations between barriers and
      quitting status 1 year later, but the number of cigarettes per day was
      consistently related to the likelihood of quitting 1 year later, regardless of
      SES. CONCLUSION: Despite the limited generalizability to racially diverse
      populations and different geographic locations, the results suggest perceived
      barriers may not differ by SES or predict quitting among young adults; however,
      nicotine dependence may play an important role.

PMID- 29214846
TI  - The Assessment of Emotional Reactivity Across Negative and Positive Emotions:
      Development and Validation of the Perth Emotional Reactivity Scale (PERS).
AB  - The Perth Emotional Reactivity Scale (PERS) is a newly developed 30-item self
      report measure of emotional reactivity (affective style). The PERS measures the
      typical ease of activation, intensity, and duration of one's emotional responses,
      and importantly does so for negative and positive emotions separately. We
      examined the psychometric properties of the PERS in an adult community sample ( N
      = 183). Confirmatory and exploratory factor analyses supported the capacity of
      the PERS to measure separate negative and positive reactivity factors, and to
      distinguish between the activation, intensity, and duration aspects of
      reactivity. All items of the PERS had strong loadings on their intended factor.
      Concurrent validity was supported via congruent correlations with other emotion
      measures, and internal reliability was good to excellent for all PERS scales and
      subscales. Overall, the PERS appears to have good psychometric properties, and
      thus has promising utility for research and clinical settings.

PMID- 29214847
TI  - Introducing a New Assessment Tool for Measuring Ethnic-Racial Identity: The Cross
      Ethnic-Racial Identity Scale-Adult (CERIS-A).
AB  - In this article, we examined the psychometric properties of scores on a new
      instrument, the Cross Ethnic-Racial Identity Scale-Adult (CERIS-A) for use across
      different ethnic and racial groups. The CERIS-A measures seven ethnic-racial
      identity attitudes-assimilation, miseducation, self-hatred, anti-dominant,
      ethnocentricity, multiculturalist inclusive, and ethnic-racial salience.
      Participants consisted of 803 adults aged 18 to 76, including African Americans
      (19.3%), Asian Americans (17.6%), European Americans (37.0%), and Latino/as
      (17.8%). Analyses indicated that CERIS-A scores were reliable, and configural,
      metric, and scalar invariance were supported for the seven factors across gender;
      however, Miseducation, Ethnic-Racial Salience, and Ethnocentricity scores
      achieved only metric invariance across ethnic-racial groups. Self-Hatred, Ethnic
      Racial Salience, Anti-Dominant, and Ethnocentricity scores were significantly and
      meaningfully related to race-based rejection sensitivity scores, providing
      evidence of convergent validity. We concluded that the CERIS-A is a potentially
      useful instrument for examining ethnic-racial identity attitudes across multiple
      racial/ethnic subgroups in the United States.

PMID- 29214845
TI  - High HIV-1 RNA Among Newly Diagnosed People in Botswana.
AB  - HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to
      determine whether HIV-1 RNA level was associated with prior knowledge of HIV
      status among treatment-naive HIV-infected individuals in Botswana, a country with
      high rates of antiretroviral treatment (ART) coverage. This information may be
      helpful in targeting HIV diagnosis and treatment efforts in similar high HIV
      prevalence settings in a population-based survey. HIV-infected individuals were
      identified during a household survey performed in 30 communities across Botswana.
      ART-naive persons with detectable HIV-1 RNA (>400 copies/mL) were divided into
      two groups, newly diagnosed and individuals tested in the past who knew about
      their HIV infection at the time of household visit, but had not taken ART. Levels
      of HIV-1 RNA were compared between groups, overall and by age and gender. Among
      815 HIV-infected ART-naive persons with detectable virus, newly diagnosed
      individuals had higher levels of HIV-1 RNA (n = 490, median HIV-1 RNA 4.35,
      interquartile range (IQR) 3.79-4.91 log10 copies/mL) than those who knew about
      their HIV-positive status (n = 325, median HIV-1 RNA 4.10, IQR 3.55-4.68 log10
      copies/mL; p values <.001, but p value = .011 after adjusting for age and
      gender). A nonsignificant trend for higher HIV-1 RNA was found among newly
      diagnosed men 30 years of age or older (median HIV-1 RNA 4.58, IQR 4.07-5.02
      log10 copies/mL vs. 4.17, 3.61-4.71 log10 copies/mL). Newly diagnosed individuals
      have elevated levels of HIV-1 RNA. This study highlights the need for early
      diagnosis and treatment of HIV infection for purposes of HIV epidemic control,
      even in a setting with high ART coverage.

PMID- 29214848
TI  - The Strengths and Difficulties Questionnaire: Factor Structure of the Father
      Report and Parent Agreement in 2-Year-Old Children.
AB  - There is limited research on the preschool version of the Strengths and
      Difficulties Questionnaire (SDQ), and comparisons between mothers and fathers as
      informants and whether the factor structure shows measurement invariance across
      parents is lacking. Our study involved mothers ( n = 6,246) and fathers ( n =
      3,759) of 2-year-old children from the Growing Up in New Zealand birth cohort.
      Confirmatory factor analysis was used to evaluate the factor structure of the SDQ
      and test for measurement invariance across mothers and fathers. For fathers, we
      found support for a modified five-factor model that accounts for a positive
      construal method effect. Internal consistency was good for measures except peer
      problems. Full measurement invariance of this modified model was found across
      mothers and fathers, and parents showed moderate agreement in their SDQ ratings
      (0.34 <= r <= 0.44). More research is needed on whether mother- and father
      reports differ in sensitivity when screening for early childhood psychiatric
      disorders.

PMID- 29214849
TI  - The Dimensions of Ruminative Thinking: One for All or All for One.
AB  - The Ruminative Thought Scale (RTS) was developed to measure the ruminative
      thinking style, presumably common to various psychopathological disorders.
      However, prior factor-analytic research was inconclusive regarding
      unidimensionality versus multidimensionality of the RTS. The present study was
      conducted on a large, heterogeneous Serbian sample ( N = 838). A subsample was
      retested 6 months later providing information about symptoms of depression and
      various anxiety symptoms. Results showed that a bifactor model of the RTS
      (representing one general and four group factors) had a better fit than the
      second-order and one-factor models. The subscale scores were not prospective
      predictors of symptoms of depression and anxiety, over and above the contribution
      of the total score. The RTS is a reliable transdiagnostic measure of repetitive
      thinking. Although there is some clustering of more homogeneous items, there is
      not enough evidence to support interpretation of the subscales.

PMID- 29214850
TI  - Rejoinder.

PMID- 29214852
TI  - Factor Structure of the Brief Comprehensive Effects of Alcohol Scale in
      Adolescents.
AB  - Alcohol use among adolescents is a public health concern; therefore, it is
      important that studies that examine factors associated with adolescent drinking
      behaviors utilize measures that are well-validated for use with this population.
      The current study examined the factor structure and convergent validity of the
      Brief Comprehensive Effects of Alcohol scale, a measure of alcohol outcome
      expectancies and evaluations of expected outcomes, among adolescents ( N = 1,074;
      50% girls; Mage = 15.96 years, SD = 1.13, range = 13-18; 74% White) drawn from
      three independent studies ( nsite 1 = 594; nsite 2 = 97; and nsite 3 = 383).
      Results yielded support for a four-factor structure for alcohol expectancies and
      two-factor structure for valuations. Moreover, the factor structure was partially
      or fully invariant across gender, age, and site. Thus, findings are similar, yet
      unique, to those identified in college samples. The convergent validity of the
      modified measure was supported, suggesting that the Brief Comprehensive Effects
      of Alcohol scale may be useful for assessing adolescents' beliefs about alcohol.

PMID- 29214851
TI  - Weight and Veterans' Environments Study (WAVES) I and II: Rationale, Methods, and
      Cohort Characteristics.
AB  - PURPOSE: To present the rationale, methods, and cohort characteristics for 2
      complementary "big data" studies of residential environment contributions to body
      weight, metabolic risk, and weight management program participation and
      effectiveness. DESIGN: Retrospective cohort. SETTING: Continental United States.
      PARTICIPANTS: A total of 3 261 115 veterans who received Department of Veterans
      Affairs (VA) health care in 2009 to 2014, including 169 910 weight management
      program participants and a propensity score-derived comparison group.
      INTERVENTION: The VA MOVE! weight management program, an evidence-based lifestyle
      intervention. MEASURES: Body mass index, metabolic risk measures, and MOVE!
      participation; residential environmental attributes (eg, food outlet availability
      and walkability); and MOVE! program characteristics. ANALYSIS: Descriptive
      statistics presented on cohort characteristics and environments where they live.
      RESULTS: Forty-four percent of men and 42.8% of women were obese, whereas 4.9% of
      men and 9.9% of women engaged in MOVE!. About half of the cohort had at least 1
      supermarket within 1 mile of their home, whereas they averaged close to 4
      convenience stores (3.6 for men, 3.9 for women) and 8 fast-food restaurants (7.9
      for men, 8.2 for women). Forty-one percent of men and 38.6% of women did not have
      a park, and 35.5% of men and 31.3% of women did not have a commercial fitness
      facility within 1 mile. CONCLUSION: Drawing on a large nationwide cohort residing
      in diverse environments, these studies are poised to significantly inform policy
      and weight management program design.

PMID- 29214853
TI  - Psychometric Properties of the Satisfaction With Life Scale in People With
      Traumatic Brain, Spinal Cord, or Burn Injury: A National Institute on Disability,
      Independent Living, and Rehabilitation Research Model System Study.
AB  - This study evaluated the measurement properties of the Satisfaction With Life
      Scale (SWLS) in a sample of 17,897 people with spinal cord injury (48%, n =
      8,566), traumatic brain injury (44%, n = 7,941), and burn injury (8%, n = 1,390),
      1 year following injury. We examined measurement invariance across the groups,
      unidimensionality, local independence, reliability from a classical test and item
      response theory (IRT) framework, and fit to a unidimensional IRT model. The
      results support unidimensionality and local independence of the SWLS. Reliability
      was adequate from a classical test and IRT perspective. IRT analysis found that
      the SWLS could be improved by using only five response categories rather than
      seven and by removing the fifth item, "If I could live my life over, I would
      change almost nothing." This item functions poorly and reduces instrument
      reliability. With these revisions, the SWLS is a useful instrument to monitor an
      important outcome of trauma rehabilitation.

PMID- 29214854
TI  - Prognostic Factors in Diabetic Foot Ulcer.

PMID- 29214855
TI  - Repetitive Negative Thinking as a Transdiagnostic Predictor of Depression and
      Anxiety Symptoms in Adolescents.
AB  - Repetitive negative thinking (RNT) is a transdiagnostic process associated with
      numerous emotional disorders. Most measures of RNT are disorder-specific,
      limiting utility in comorbid populations. Transdiagnostic measures of RNT have
      been developed in adults and are associated with anxiety and depression. However,
      a transdiagnostic measure is needed to assess RNT in adolescents as a potential
      vulnerability factor for emotional disorders. This study validates a
      transdiagnostic measure of RNT-Repetitive Thinking Questionnaire-10 (RTQ-10)-in
      adolescents ( N = 840, Mage = 15.7 years). Exploratory and confirmatory factor
      analyses supported a unidimensional structure. The RTQ-10 manifested good
      internal consistency and measurement invariance across genders and age. RNT was
      equally associated with anxiety and depression symptoms irrespective of gender or
      age. Convergent validity was demonstrated by correlations with disorder-specific
      measures of RNT. These findings support the RTQ-10 as a reliable and valid
      transdiagnostic measure of RNT in adolescents.

PMID- 29214856
TI  - Physical Activity Interventions in Faith-Based Organizations: A Systematic
      Review.
AB  - OBJECTIVE: To review and assess the effectiveness of physical activity
      interventions delivered in faith-based organizations. DATA SOURCE: We searched
      the Cochrane Library, DoPHER, EMBASE, LILACS, MEDLINE, PsycINFO, WHO ICTRP, and
      Clinicaltrials.gov databases until January 2016, without restriction of language
      or publication date. STUDY INCLUSION AND EXCLUSION CRITERIA: Randomized and
      nonrandomized controlled trials investigating physical activity interventions for
      adults delivered in faith-based organizations. DATA EXTRACTION: Two independent
      reviewers extracted data and assessed study methodological quality. DATA
      SYNTHESIS: We used relative risk and mean difference with 95% confidence interval
      to estimate the effect of the interventions on measures of physical activity,
      physical fitness, and health. RESULTS: The review included 18 studies. Study
      participants were predominantly female, and the majority of trials were conducted
      in the United States. Study heterogeneity did not allow us to conduct meta
      analyses. Although interventions delivered in faith-based organizations increased
      physical activity and positively influenced measures of health and fitness in
      participants, the quality of the evidence was very low. CONCLUSION: Faith-based
      organizations are promising settings to promote physical activity, consequently
      addressing health disparities. However, high-quality randomized clinical trials
      are needed to adequately assess the effectiveness of interventions delivered in
      faith-based organizations.

PMID- 29214857
TI  - Feeding time can alleviate negative effects of heat stress on performance, meat
      quality and health status of turkey.
AB  - 1. A total of 180 one-day-old turkeys were randomly assigned to 6 equal groups to
      investigate the effect of feeding time on growth performance, carcass
      characteristics, meat quality, leg problems and physiological responses of
      growing turkeys under the high temperature conditions of summer. 2. Birds of the
      first group were ad libitum fed and were considered as the controls (C). The
      second group (T1) was given 80% of diet in the morning and 20% of diet in the
      afternoon, the third group (T2) was given 60% of diet in the morning and 40% of
      diet in the afternoon, the fourth group (T3) was given 40% of diet in the morning
      and 60% of diet in the afternoon, the fifth group (T4) was given 20% of diet in
      the morning and 80% of diet in the afternoon and the sixth group (T5) was given
      100% of diet in the afternoon. 3. Body weight, body weight gain and feed
      conversion ratio were improved with T2, T3, T4 and T5 in comparison to control or
      T1 under heat stress conditions. No significant impacts on carcass traits and
      meat quality due to changing the time of feeding were seen, except for tenderness
      and juiciness. 4. Feeding in the afternoon (100%) decreased body temperature and
      tonic immobility test score, which were positively related with the health
      condition of the birds. 5. The incidence of leg problems, plumage condition and
      breast blisters were not significantly different among the experimental groups.
      6. It is concluded that feeding turkeys mainly or totally in the afternoon (T4
      and T5, birds were fed with 80% or 100% of the diet in the afternoon) can be used
      as a strategy and a managerial tool for improving growth rate, feed utilisation,
      carcass and meat quality, as well as health status of growing turkeys reared
      under hot climate conditions.

PMID- 29214858
TI  - Cognitive Impairment, Dementia, and Personality Stability Among Older Adults.
AB  - There is contrasting evidence on personality stability in advanced age, and
      limited knowledge on the impact of cognitive impairment and dementia on trait
      stability. Group- and individual-level longitudinal analyses of the five major
      dimensions of personality assessed twice over 4 years ( N = 9,935) suggest that
      rank-order stability was progressively lower with advancing age (from rtt = 0.68
      for age 50 to 60 years to rtt = 0.58 for age >80 years). Stability was low in the
      dementia group ( rtt = 0.43), and this was not simply due to lower reliability
      given that internal consistency remained adequate in the dementia group. Among
      individuals with no cognitive impairment or dementia, there was no association
      between stability and age ( rtt = 0.70 even for age >80 years). These results
      suggest that the lower personality stability in older adults is not due to age
      but cognitive impairment and dementia.

PMID- 29214860
TI  - A Comparison of Unidimensionality and Measurement Precision of the Narcissistic
      Personality Inventory and the Narcissistic Admiration and Rivalry Questionnaire.
AB  - The current study compares the closeness to unidimensionality (CU) and
      measurement precision (MP) of the Narcissistic Personality Inventory (NPI)-with
      either a pairwise forced-choice or 5-point Likert-type scale response format-to
      the Narcissistic Admiration and Rivalry Questionnaire (NARQ). Minimum rank factor
      analysis and item information curves from item response models were utilized. The
      results mainly confirmed our expectations that NPI subscales are lower in CU and
      MP compared with NARQ subscales when the NPI was administered with its
      traditional forced-choice response format. When the NPI was administered with a 5
      point Likert-type scale response format, the NPI subscale Leadership/Authority
      and NPI Grandiose Exhibitionism showed similarly high levels of CU and MP as the
      two NARQ subscales. While the NPI subscale Entitlement/Exploitativeness had a
      higher CU than the NARQ subscales it showed considerably lower levels of MP.

PMID- 29214859
TI  - Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical
      Alzheimer's Disease.
AB  - In spite of advances in neuroimaging and other brain biomarkers to assess
      preclinical Alzheimer's disease (AD), cognitive assessment has relied on
      traditional memory paradigms developed well over six decades ago. This has led to
      a growing concern about their effectiveness in the early diagnosis of AD which is
      essential to develop preventive and early targeted interventions before the
      occurrence of multisystem brain degeneration. We describe the development of
      novel tests that are more cognitively challenging, minimize variability in
      learning strategies, enhance initial acquisition and retrieval using cues, and
      exploit vulnerabilities in persons with incipient AD such as the susceptibility
      to proactive semantic interference, and failure to recover from proactive
      semantic interference. The advantages of various novel memory assessment
      paradigms are examined as well as how they compare with traditional
      neuropsychological assessments of memory. Finally, future directions for the
      development of more effective assessment paradigms are suggested.

PMID- 29214861
TI  - Podiatry Ankle Duplex Scan: Readily Learned and Accurate in Diabetes.
AB  - We aimed to train podiatrists to perform a focused duplex ultrasound scan (DUS)
      of the tibial vessels at the ankle in diabetic patients; podiatry ankle (PodAnk)
      duplex scan. Thirteen podiatrists underwent an intensive 3-hour long simulation
      training session. Participants were then assessed performing bilateral PodAnk
      duplex scans of 3 diabetic patients with peripheral arterial disease.
      Participants were assessed using the duplex ultrasound objective structured
      assessment of technical skills (DUOSATS) tool and an "Imaging Score". A total of
      156 vessel assessments were performed. All patients had abnormal waveforms with a
      loss of triphasic flow. Loss of triphasic flow was accurately detected in 145
      (92.9%) vessels; the correct waveform was identified in 139 (89.1%) cases.
      Participants achieved excellent DUOSATS scores (median 24 [interquartile range:
      23-25], max attainable score of 26) as well as "Imaging Scores" (8 [8-8], max
      attainable score of 8) indicating proficiency in technical skills. The mean time
      taken for each bilateral ankle assessment was 20.4 minutes (standard deviation +/
      6.7). We have demonstrated that a focused DUS for the purpose of vascular
      assessment of the diabetic foot is readily learned using intensive simulation
      training.

PMID- 29214862
TI  - Screening for Problematic Worry in Adults With a Single Item From the Penn State
      Worry Questionnaire.
AB  - As the rapid assessment of mental health is a growing need, a quick and valid
      tool for the early detection of symptoms that can be flexibly deployed across a
      range of contexts may be especially beneficial. This is particularly true of
      anxiety problems, which when undetected contribute to health care costs and lost
      work productivity. Data from more than 10,000 respondents (primarily female
      undergraduates) were used to test whether a single item from the popular Penn
      State Worry Questionnaire could serve as a screening tool in settings where
      administration of the full scale is undesirable. Items were evaluated by
      examining item response theory models, screening capabilities, stability over
      time, convergence with other anxiety and depression measures, and a response time
      analysis that assessed how quickly participants responded to each item. Item 15
      ("I worry all the time") emerged as the strongest item: It was the most
      discriminating and reliable item, had sensitivity and specificity similar to the
      full scale, had the highest 1-month and 1-year retest coefficients, the highest
      convergent correlations with measures of anxiety and depression, and was
      responded to significantly faster than any other item. We suggest that in time
      limited contexts, this item is suitable for screening.

PMID- 29214863
TI  - Impact of a Weight Management Intervention on Eating Competence: Importance of
      Measurement Interval in Protocol Design.
AB  - PURPOSE: To examine changes in eating competence (EC) in 12-month weight loss
      intervention. DESIGN: Randomized, parallel-arm with weight loss phase (baseline
      to month 4) and weight-maintenance phase (months 4-12). SETTING: Face-to-face in
      University classrooms, supervised and self-directed fitness sessions at
      University fitness center, and home. PARTICIPANTS: Premenopausal, mostly college
      educated Pennsylvania women, body mass index >25 (n = 101). INTERVENTION: Twenty
      eight, 1-hour classes tailored for extremes of the Dietary Guidelines' fat
      recommendations, based on social cognitive theory, problem-based learning
      delivery over 12 months. Exercise component included supervised and self-directed
      stretching, aerobics, and strength training. MEASURES: Anthropometrics, lipid
      profile, blood pressure, 24-hour dietary recalls, cognitive behavioral measures,
      Satter Eating Competence Inventory (ecSI). ANALYSIS: General linear model
      repeated measures analysis of variance for outcome variables. RESULTS: A total of
      40% (n = 40) completed the ecSI. Overall, education and supervised exercise
      session attendance were 77% and 88%, respectively. Similar weight loss for lower
      and moderate fat groups (6.7 kg and 5.4 kg). The EC was unchanged baseline to
      month 4 but increased significantly from months 4 to 12, baseline to month 12 for
      both groups. The EC change baseline to month 12 was inversely associated with
      weight change from baseline to months 4 and 12. CONCLUSION: Weight management
      interventions, likely to introduce concerns with eating attitudes, behaviors, and
      foods, can reduce EC. Short-term measurement of EC change captures these
      consequent adjustments without opportunity to regain self-efficacy. Extending the
      measurement interval better reflects intervention impact on EC.

PMID- 29214864
TI  - Radial Versus Femoral Access for Coronary Angiography.

PMID- 29214865
TI  - Automatic Seizure Detection Based on Morphological Features Using One-Dimensional
      Local Binary Pattern on Long-Term EEG.
AB  - Epileptic neurological disorder of the brain is widely diagnosed using the
      electroencephalography (EEG) technique. EEG signals are nonstationary in nature
      and show abnormal neural activity during the ictal period. Seizures can be
      identified by analyzing and obtaining features of EEG signal that can detect
      these abnormal activities. The present work proposes a novel morphological
      feature extraction technique based on the local binary pattern (LBP) operator.
      LBP provides a unique decimal value to a sample point by weighing the binary
      outcomes after thresholding the neighboring samples with the present sample
      point. These LBP values assist in capturing the rising and falling edges of the
      EEG signal, thus providing a morphologically featured discriminating pattern for
      epilepsy detection. In the present work, the variability in the LBP values is
      measured by calculating the sum of absolute difference of the consecutive LBP
      values. Interquartile range is calculated over the preprocessed EEG signal to
      provide dispersion measure in the signal. For classification purpose, K-nearest
      neighbor classifier is used, and the performance is evaluated on 896.9 hours of
      data from CHB-MIT continuous EEG database. Mean accuracy of 99.7% and mean
      specificity of 99.8% is obtained with average false detection rate of 0.47/h and
      sensitivity of 99.2% for 136 seizures.

PMID- 29214866
TI  - The price of success-health economics of personalized diffuse large B-cell
      lymphoma treatment.

PMID- 29214867
TI  - Disease site as a determinant of survival outcome in patients with primary
      cutaneous peripheral T-cell lymphoma, unspecified: an analysis of 4057 cases from
      the US National Cancer Database.
AB  - Primary cutaneous peripheral T-cell lymphoma, unspecified (PCPTL) accounts for
      <6% of cutaneous T-cell lymphoma cases. Due to its rarity, no large study exists
      in the literature on PCPTL. Among 4057 patients with PCPTL diagnosed from 2004 to
      2014 in the National Cancer Database, 428, 913, 517, 754, and 1435 had lesions
      localized primarily to the upper extremity, head and neck, lower extremity,
      trunk, and overlapping lesion or unspecified site, respectively. PCPTL that
      primarily involved the head and neck had the longest overall survival (OS),
      followed by PCPTL that primarily involved the trunk, upper extremity, and lower
      extremity. Patients with lesions localized to the lower extremity had
      significantly shorter OS when compared to those with disease localized to other
      primary sites after adjusting for confounding factors. The difference in OS among
      disease sites was only significant in stage I disease, but not higher stages, and
      persisted in younger patients.

PMID- 29214868
TI  - Sulfasalazine induces mitochondrial dysfunction and renal injury.
AB  - Sulfasalazine is a commonly used drug for the treatment of rheumatoid arthritis
      and inflammatory bowel disease. There are several cases of renal injury encompass
      sulfasalazine administration in humans. The mechanism of sulfasalazine adverse
      effects toward kidneys is obscure. Oxidative stress and its consequences seem to
      play a role in the sulfasalazine-induced renal injury. The current investigation
      was designed to investigate the effect of sulfasalazine on kidney mitochondria.
      Rats received sulfasalazine (400 and 600 mg/kg/day, oral) for 14 consecutive
      days. Afterward, kidney mitochondria were isolated and assessed. Sulfasalazine
      induced renal injury was biochemically evident by the increase in serum blood
      urea nitrogen (BUN), gamma-glutamyl transferase (gamma-GT), and creatinine (Cr).
      Histopathological presentations of the kidney in sulfasalazine-treated animals
      revealed by interstitial inflammation, tubular atrophy, and tissue necrosis.
      Markers of oxidative stress including an increase in reactive oxygen species
      (ROS) and lipid peroxidation (LPO), a defect in tissue antioxidant capacity, and
      glutathione (GSH) depletion were also detected in the kidney of sulfasalazine
      treated groups. Decreased mitochondrial succinate dehydrogenase activity (SDA),
      mitochondrial depolarization, mitochondrial GSH depletion, increase in
      mitochondrial ROS, LPO, and mitochondrial swelling were also evident in
      sulfasalazine-treated groups. Current data suggested that oxidative stress and
      mitochondrial injury might be involved in the mechanism of sulfasalazine-induced
      renal injury.

PMID- 29214869
TI  - The Relationship Between the Personality Inventory for the DSM-5 (PID-5) and the
      Psychotic Disorder in a Clinical Sample.
AB  - Recent studies have successfully investigated the validity of the DSM-5
      Alternative Model for Personality Disorders. In a final sample of 174 psychiatric
      patients, the present study examined the relationship between the Personality
      Inventory for the DSM-5 (PID-5) and syndromal psychosis. Results showed that
      patients diagnosed with versus without a psychotic disorder significantly
      differed on all PID-5 domains except Antagonism. Discriminant function analysis
      indicated that lower Detachment, lower Negative Affect, lower Disinhibition, and
      higher Psychoticism best discriminated patients with a psychotic disorder from
      patients with other psychiatric conditions. Subsequent stepwise discriminant
      analysis on all facet scales of the contributing PID-5 domains revealed that
      higher Unusual Beliefs, lower Depressivity, and lower Distractibility contributed
      the most to this differentiation. PID-5 Psychoticism scores showed moderate
      correlations with current psychotic symptoms and were not influenced by dose of
      antipsychotic medication. Our results support the ability of the PID-5 to
      discriminate between patients with and without psychotic disorder.

PMID- 29214870
TI  - Advances in cell-free protein array methods.
AB  - INTRODUCTION: Cell-free protein microarrays represent a special form of protein
      microarray which display proteins made fresh at the time of the experiment,
      avoiding storage and denaturation. They have been used increasingly in basic and
      translational research over the past decade to study protein-protein
      interactions, the pathogen-host relationship, post-translational modifications,
      and antibody biomarkers of different human diseases. Their role in the first
      blood-based diagnostic test for early stage breast cancer highlights their value
      in managing human health. Cell-free protein microarrays will continue to evolve
      to become widespread tools for research and clinical management. Areas covered:
      We review the advantages and disadvantages of different cell-free protein arrays,
      with an emphasis on the methods that have been studied in the last five years. We
      also discuss the applications of each microarray method. Expert commentary: Given
      the growing roles and impact of cell-free protein microarrays in research and
      medicine, we discuss: 1) the current technical and practical limitations of cell
      free protein microarrays; 2) the biomarker discovery and verification pipeline
      using protein microarrays; and 3) how cell-free protein microarrays will advance
      over the next five years, both in their technology and applications.

PMID- 29214871
TI  - Rare manifestations of extramedullary myeloma: testicular plasmacytomas.

PMID- 29214873
TI  - A highly sensitive miR-195 nanobiosensor for early detection of Parkinson's
      disease.
AB  - Early detection of Parkinson's disease (PD), as a dangerous neurodegenerative
      disease, is a key factor in the therapy or prevention of further development of
      this disease. We developed an electrochemical nanobiosensor for early detection
      of PD based on the quantification of circulating biomarker, miR-195. Exfoliated
      graphene oxide (EGO) and gold nanowires (GNWs) were used to modify the surface of
      screen-printed carbon electrode. A single-strand thiolated probe was designed for
      specific hybridization with target miRNA (miR-195), and doxorubicin was used as
      an electrochemical indicator for differential pulse voltammetry measurements. The
      results of scanning electron microscope imaging and cyclic voltammetry
      experiments confirmed the accuracy of the working electrode modification steps.
      The results of analytical performance nanobiosensor showed a high sensitivity of
      the biosensing with 2.9 femtomolar detection limit and dynamic range of 10.0
      900.0 femtomolar. In addition, good selectivity for target miRNA over non
      specific oligonucleotides (one and three base replacement in target miRNA, and
      non-complementary) was achieved. The results of real human serum analysis did not
      show any interference in the function of the biosensor. Based on the results, the
      miR-195 electrochemical nanobiosensor could be suggested for clinicians in the
      medical diagnosis of PD.

PMID- 29214872
TI  - Measuring reliable change in cognition using the Edinburgh Cognitive and
      Behavioural ALS Screen (ECAS).
AB  - BACKGROUND: Cognitive impairment affects approximately 50% of people with
      amyotrophic lateral sclerosis (ALS). Research has indicated that impairment may
      worsen with disease progression. The Edinburgh Cognitive and Behavioural ALS
      Screen (ECAS) was designed to measure neuropsychological functioning in ALS, with
      its alternate forms (ECAS-A, B, and C) allowing for serial assessment over time.
      OBJECTIVE: The aim of the present study was to establish reliable change scores
      for the alternate forms of the ECAS, and to explore practice effects and test
      retest reliability of the ECAS's alternate forms. METHOD: Eighty healthy
      participants were recruited, with 57 completing two and 51 completing three
      assessments. Participants were administered alternate versions of the ECAS
      serially (A-B-C) at four-month intervals. Intra-class correlation analysis was
      employed to explore test-retest reliability, while analysis of variance was used
      to examine the presence of practice effects. Reliable change indices (RCI) and
      regression-based methods were utilized to establish change scores for the ECAS
      alternate forms. RESULTS: Test-retest reliability was excellent for ALS Specific,
      ALS Non-Specific, and ECAS Total scores of the combined ECAS A, B, and C (all >
      .90). No significant practice effects were observed over the three testing
      sessions. RCI and regression-based methods produced similar change scores.
      CONCLUSION: The alternate forms of the ECAS possess excellent test-retest
      reliability in a healthy control sample, with no significant practice effects.
      The use of conservative RCI scores is recommended. Therefore, a change of >=8,
      >=4, and >=9 for ALS Specific, ALS Non-Specific, and ECAS Total score is required
      for reliable change.

PMID- 29214874
TI  - Immunophenotypic and laboratory features of t(11;14)(q13;q32)-positive plasma
      cell neoplasms.
AB  - The t(11;14)(q13;32)-positive plasma cell neoplasms (PCNs) are common. In light
      of their lymphoplasmacytoid features and CD20 expression, we speculated that they
      may share laboratory features with B-cell lymphomas with plasmacytic
      differentiation (BCL-PCDs). We investigated flow cytometric CD19 and CD45
      expression, DNA ploidy index and M-protein subtype in 416 t(11;14)-positive PCNs,
      as well as control groups (88 BCL-PCDs and 81 t(11;14)-negative PCNs). The plasma
      cells from the t(11;14)-positive PCNs were largely CD19-/CD45-, similar to the
      t(11;14)-negative PCNs and unlike the BCL-PCD plasma cells (p < .0001). 79% of
      the t(11;14)-positive PCNs were diploid, which was significantly more than in
      t(11;14)-negative PCNs (p < .0001) and significantly less than in the BCL-PCDs (p
      < .001). Although IgM secretion was common in BCL-PCDs (80%) and rare in PCNs
      (3%), most IgM PCNs (92%) were t(11;14)-positive. These findings may be helpful
      in evaluating specimens with clonal plasma cells in the reference laboratory
      setting.

PMID- 29214875
TI  - Genetic polymorphisms of arylamine N-acetyltransferases 1 and 2 and the
      likelihood of developing pediatric acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is one of the main causes of death in children
      and is associated with both genetic susceptibility and environmental factors.
      Genes encoding the arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2)
      isoenzymes are highly polymorphic among populations. Single-nucleotide
      polymorphism analysis was performed by real-time polymerase chain reaction from
      the genomic DNA of 225 healthy subjects and 57 children with ALL diagnoses.
      Significant associations were found between the development of ALL and the
      presence of the haplotypes NAT1*3 (Odds ratio [OR], 2.1), NAT1*4 (OR, 1.92),
      NAT2*6B (OR, 3.30), NAT2*6J (OR, 3.25) and NAT2*7A (OR, 2.45) and the NAT1 rapid
      (OR, 6.69) and NAT2 slow phenotypes (OR, 2.95). Our results indicate that
      haplotypes that provide rapid NAT1 and slow NAT2 acetylating phenotypes may
      influence the development of ALL in children.

PMID- 29214876
TI  - Assessing the risk of cardiac toxicity after contemporary treatment for Hodgkin
      lymphoma: a systematic review.

PMID- 29214877
TI  - A pair of enantiomeric 5-oxabicyclic[4.3.0]lactam derivatives and one new
      polyketide from the marine-derived fungus Penicillium griseofulvum.
AB  - A pair of enantiomeric 4-oxabicyclic[4.3.0]lactam derivatives, (+)- and (-)
      penicilactam A (1), and one new polyketide derivative penicitrinone F (2) were
      isolated from the marine-derived fungus Penicillium griseofulvum GT-10. Their
      structures and absolute configurations were elucidated through extensive
      spectroscopic analyses combined with the calculated ECD spectra. Penicitrinone F
      (2) had moderate inhibitory activity towards Bacillus subtilis with a MIC value
      of 6.3 MUM.

PMID- 29214878
TI  - Combination of IKZF1 deletion and early molecular response show significant roles
      on prognostic stratification in Philadelphia chromosome-positive acute
      lymphoblastic leukemia patients.
AB  - We retrospectively analyzed the samples collected from 66 patients with Ph+ALL
      enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated
      2-year OS and DFS were 51.7 +/- 11.7% and 26.9 +/- 11.6%, 3-year OS and DFS were
      31.6 +/- 12.0% and 23.4 +/- 11.6%. By combining IKZF1 deletion and early
      molecular responses, we redefined the patients as low, intermediate, and high
      risk 3 groups separately. Patients with double negative in IKZF1 and early
      molecular response experienced significant superior survival, while patients with
      double positive would have the worst outcome, and patients who were one or the
      other with IKZF1 deletion or MRD status had intermediate outcome. Significant
      differences were found among 3 groups in regard to both OS (p < .001) and DFS (p
      < .001). Our findings suggest that Ph+ALL is a heterogeneous group of diseases
      with significantly different prognosis. Combination of IKZF1 deletion and MRD
      status enable better risk stratification of patients for assignment to optimal
      therapeutic strategies.

PMID- 29214879
TI  - Inappropriate treatment in Helicobacter pylori eradication failure: a
      retrospective study.
AB  - BACKGROUND: In recent years, success rates of empirical H. pylori therapies have
      fallen in many countries. Although antibiotic resistance and poor adherence are
      described as the main factors for treatment failure, in China, iatrogenic factors
      also play an important role. OBJECTIVE: To investigate why patients experienced
      multiple failures, we performed a retrospective, single center study using
      questionnaires to identify causes of treatment failure other than antibiotic
      resistance. METHODS: This study was conducted from January 2016 to July 2017 in a
      general hospital. Patients with at least two H. pylori treatment failures who
      completed the questionnaire were entered. The survey covered characteristics of
      the study population, regimens used, and adherence to therapy. RESULTS: Two
      hundred and ninety three patients were included in the final analysis. The top
      three most antibiotic combinations as the first-line treatment were a PPI plus
      clarithromycin-metronidazole (24.6%, 72/293), clarithromycin-levofloxacin (23.5%,
      69/293) and clarithromycin-amoxicillin (21.5%, 63/293). Clarithromycin-containing
      regimens were repeatedly used in 178 patients (60.8%) and levofloxacin-containing
      regimens repeatedly in 88 patients (30.0%). Fifty patients (17.1%) had poor
      adherence per treatment history and 32 (10.9%) stopped treatment because of
      nonmedical reasons. CONCLUSIONS: In order to increase the success of H. pylori
      eradication therapy, the effect of prior therapies needs to be given more
      consideration. Patient education to enhance adherence also needs to be improved.

PMID- 29214881
TI  - Ecotopic viral integration site 1 (EVI1) transcriptionally targets talin1 (TLN1)
      and upregulates its expression in chronic myeloid leukemia.

PMID- 29214880
TI  - Low ascitic fluid total protein levels is not associated to the development of
      spontaneous bacterial peritonitis in a cohort of 274 patients with cirrhosis.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a complication to
      decompensated cirrhosis. Fluoroquinolones may prevent SBP. However, predictive
      markers for SBP are wanted. Guidelines suggest that patients with ascitic fluid
      protein below 15 g/l receive fluoroquinolones to prevent SBP. This study aimed to
      assess the clinical utility of low ascitic fluid protein in predicting SBP in
      patients with cirrhosis and ascites. METHODS: A total of 274 patients with
      cirrhosis and ascites underwent paracentesis between January 2010 and June 2015.
      Patients were followed until two years, development of SBP, initiation of
      ciprofloxacin, death or liver transplantation. Data were compared between groups
      of patients with 'high' or 'low' ascitic protein. RESULTS: SBP developed in 31
      patients (11.3%). No difference in mean ascitic fluid protein levels were found
      (SBP, mean: 8.5 g/l and no SBP 8.2 g/l, p = .825). SBP developed at equal rates
      in patients with 'high' or 'low' ascitic protein (10.8% (<=15 g/l) and 14.0% (>15
      g/l), p = .599). The same trend was observed when adjusting the threshold below
      10 g/l (11.9% (<=10 g/l) and 10.2% (>10 g/l), p = .697). CONCLUSIONS: Low ascitic
      fluid protein does not predict SBP in patients with cirrhosis and ascites. Better
      markers are needed.

PMID- 29214882
TI  - Breakthrough Saprochaete Capitata infections among patients with hematological
      malignancies.

PMID- 29214883
TI  - Longitudinal structural changes in ALS: a three time-point imaging study of white
      and gray matter degeneration.
AB  - BACKGROUND: Cross-sectional imaging studies offer valuable pathological insights
      into the neurodegenerative changes of amyotrophic lateral sclerosis. However,
      clinical trials urgently require sensitive monitoring markers that can detect
      subtle progressive changes over relatively short periods of time. We have
      conducted a three time-point longitudinal study to explore anatomical patterns of
      disease spread and to determine whether MRI metrics capture longitudinal changes
      over four and eight-month intervals. METHODS: Thirty-two ALS patients were
      enrolled into a multiparametric imaging study to evaluate progressive cortical
      thickness, grey matter density and white matter alterations. Whole-brain and
      region-of-interest analyses were conducted in the precentral gyrus, corticospinal
      tracts, corpus callosum and cerebellum. Additionally, pre-symptomatic changes
      were explored in patients with no bulbar or lower limb disability. RESULTS: Our
      findings suggest that considerable white matter degeneration can be detected
      early in the course of the disease which shows limited progression over time,
      whereas grey matter pathology is relatively limited at baseline and exhibits
      relentless progression. Moreover, progressive presymptomatic structural changes
      can be identified in the bulbar and lower limb representations of the precentral
      gyrus. CONCLUSIONS: Our longitudinal imaging study confirms that MRI metrics
      readily capture progressive changes in ALS. Our data also indicate that white
      matter metrics are of potential use as diagnostic markers, and grey matter
      measures may be superior as monitoring biomarkers. One of the most interesting
      findings of our study is the gradually progressive cerebellar grey matter
      degeneration throughout the three time-points.

PMID- 29214884
TI  - Adjuvant intraperitoneal chemotherapy for the treatment of colorectal cancer at
      risk for peritoneal carcinomatosis: a systematic review.
AB  - BACKGROUND: The peritoneal surface is the second most common site of disease
      recurrence, after the liver, following definitive surgery for colorectal cancer.
      Adjuvant intraperitoneal (IP) chemotherapy delivered at time of surgical
      resection has the potential to delay or prevent future spread to the peritoneal
      surface and improve clinical outcome. The exact role of adjuvant IP chemotherapy
      in colorectal cancer, including its associated morbidity and mortality, is not
      well defined. STUDY DESIGN: Systematic review and pooled random effect analysis
      of comparative trials examining the addition of adjuvant IP chemotherapy compared
      to surgery alone in colorectal cancer. The primary outcome was overall survival,
      and the secondary outcomes were of post-operative morbidity and mortality.
      RESULTS: In nine colorectal cancer studies identified, seven were two-arm trials
      comparing adjuvant IP chemotherapy to surgery alone. Of these, four trials had
      outcome reporting and met criteria that allowed inclusion into a random effects
      model. Heterogeneity was measured by Cochran's Q-test (Q = 13.9; p = 0.01) and
      random effect models were utilised. Pooling eligible trials together revealed a
      0.55 odds ratio of death associated with the administration of IP chemotherapy
      compared to surgery alone (CI = 0.31, 0.98; p = 0.04). Trials selecting patients
      at elevated risk for the development of peritoneal carcinomatosis by
      clinicopathological biomarkers for administration of adjuvant IP chemotherapy
      reported more favourable overall outcomes. There was no increase in mortalities
      or IP chemotherapy-related abdominal complication rates among patients undergoing
      IP chemotherapy (OR = 1.4; CI = 0.52, 3.8; p = 0.5). CONCLUSIONS: This systematic
      review supports the use of adjuvant IP chemotherapy in resectable colorectal
      cancer at risk for peritoneal spread. Future trials should seek to standardise
      inclusion criteria and IP chemotherapy modalities to better define the role of
      this treatment in patients with resectable colorectal cancer.

PMID- 29214885
TI  - Short-term efficacy of potassium-competitive acid blocker following gastric
      endoscopic submucosal dissection: a propensity score analysis.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is a promising method for the
      resection of superficial gastric neoplasms. Vonoprazan is a novel potassium
      competitive acid blocker (P-CAB) that is currently considered as a potential
      alternative to proton pump inhibitors (PPIs) for the treatment of acid-related
      diseases. However, the utility of vonoprazan in ESD-related ulcers is unclear.
      Therefore, we compared the short-term efficacies of vonoprazan and the PPI
      lansoprazole in ESD-related ulcer healing during the first two weeks following
      intervention. METHODS: This study included 115 superficial gastric neoplasms that
      were treated by ESD at Hiraka General Hospital between April 2015 and January
      2017. Patients treated with P-CAB (20 mg vonoprazan, n = 62) or PPI (30 mg
      lansoprazole, n = 53) were compared using propensity-score matching analysis.
      Primary outcome was rate of ulcer reduction at two weeks after ESD. Secondary
      outcomes were coverage ratio of ulcer base by granulation tissue and incidence of
      postoperative bleeding. RESULTS: The rate of ulcer reduction was significantly
      higher (median [range], 80.6% [67.6%-94.5%] vs. 62.7% [33.4%-85.2%]; p < .0001)
      and coverage ratio of the ulcer base by granulation tissue was significantly
      accelerated (median [range], 84.1% [67.7%-95.3%] vs. 61.9% [12.1%-90.1%]; P <
      0.0001) in the P-CAB group compared with the PPI group. Postoperative bleeding
      was not observed in either group. CONCLUSIONS: P-CAB achieved rapid artificial
      ulcer healing with promotion of granulation tissue formation. However,
      conventional PPI with initial intravenous infusion might be sufficient for
      prevention of postoperative bleeding following gastric ESD.

PMID- 29214886
TI  - Clinical and molecular aspects of lead toxicity: An update.
AB  - Lead toxicity is a major public health issue in developed and developing
      countries. Both acute and chronic lead exposure has the potential to cause many
      deleterious systematic effects including hypertension, frank anemia, cognitive
      deficits, infertility, immune imbalances, delayed skeletal and deciduous dental
      development, vitamin D deficiency, and gastrointestinal effects. The underlying
      mechanisms for all these systemic effects have not been elucidated completely.
      However, the most plausible cause is free radical damage. In addition to this,
      lead being a divalent cation can surrogate for calcium at multiple levels
      affecting various cell signaling pathways. The molecular basis of lead exposure
      resulting in various systemic effects is being extensively explored. The reports
      include single nucleotide polymorphisms, epigenetic modifications in susceptible
      individuals, and the most recent reports also feature regulatory RNA molecules -
      miRNAs. However, many genetic targets are identified, but their possible
      mechanisms are still an area to be explored. Additional studies are needed in
      different population groups to validate the existing findings, as well as to find
      newer targets that may help in better understanding the molecular mechanisms
      contributing to lead toxicity. Furthermore, newer strategies for lead risk
      assessment becomes necessary as the previously recognized "safe" level of lead is
      also being found to be associated with negative health outcomes.

PMID- 29214888
TI  - Minimally invasive surgical approach for radicalization of incidental post
      cholecystectomy gallbladder carcinoma: safety, feasibility and outcomes.
AB  - BACKGROUND AND AIMS: Gallbladder carcinoma is a rare but aggressive malignant
      neoplasm. The incidence of intra- or post-operative incidental gallbladder
      carcinoma diagnosis following laparoscopic cholecystectomy is estimated to be 1
      2%. Aggressive re-resection is warranted as the majority of patients have
      residual disease either in the liver or the lymph nodes. However the use of a
      minimally invasive surgical approach (MISA) to perform a radicalization in these
      patients has not been investigated yet. We retrospectively analyzed surgical and
      oncologic outcome of a small selected cohort of patients with incidental
      gallbladder carcinoma whom underwent redo radicalization surgery by MISA.
      MATERIAL AND METHODS: From April 2012 to June 2014 at our department six patients
      (three females and three males) with incidental findings of gallbladder carcinoma
      pT1b (stage I) following laparoscopic cholecystectomy, and referred to our center
      from other secondary-level referral hospitals, underwent a redo surgery for
      radicalization by means of laparoscopic (n. 3) or robotic approach (n. 3). A
      retrospective analysis of prospective collected data was performed. RESULTS: The
      redo procedure consisted of a liver resection (segments IVb + V) and lymph nodes
      clearance of hepatoduodenal hilum and common hepatic artery. Conversion rate was
      zero. Median operative time was 290 (250-310) min. Estimate blood loss was 175
      (100-350) ml. Total hospital stay was 6 (5-10) days. All liver resections were
      performed without inflow vascular clamping. One patient was re-operated for
      hemoperitoneum while peri-operative mortality was zero. Oncologically, an R0
      resection was always achieved with a mean number of lymph nodes retrieved of 17,5
      (14-22). The stage of the neoplasm was confirmed in all cases but one, who was
      found to have a pN1 status (stage IIIb). At 21 (6-32) months follow-up all
      patients are alive and no recurrence has been observed. CONCLUSIONS: Our data
      suggest that radicalization of patients with stage I incidental postoperative
      gallbladder carcinoma can be done by a MISA without compromising the oncologic
      outcome. Larger studies are needed to validate these results.

PMID- 29214887
TI  - Enhanced efficacy of curcumin with phosphatidylserine-decorated nanoparticles in
      the treatment of hepatic fibrosis.
AB  - Hepatic macrophages have been considered as a therapeutic target for liver
      fibrosis treatment, and phosphatidylserine (PS)-containing nanoparticles are
      commonly used to mimic apoptotic cells that can specifically regulate macrophage
      functions, resulting in anti-inflammatory effects. This study was designed to
      test the efficacy of PS-modified nanostructured lipid carriers (mNLCs) containing
      curcumin (Cur) (Cur-mNLCs) in the treatment of liver fibrosis in a rat model.
      Carbon tetrachloride-induced liver fibrosis in rats was used as an experimental
      model, and the severity of the disease was examined by both biochemical and
      histological methods. Here, we showed that mNLCs were spherical nanoparticles
      with decreased negative zeta potentials due to PS decoration, and significantly
      increased both mean residence time and area under the curve of Cur. In the rats
      with liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting
      to the diseased liver, which was evidenced by their highest accumulation in the
      liver. As compared to all the controls, Cur-mNLCs were significantly more
      effective at reducing the liver damage and fibrosis, which were indicated by in
      Cur-mNLCs-treated rats the least increase in liver enzymes and pro-inflammatory
      cytokines in the circulation, along with the least increase in collagen fibers
      and alpha smooth muscle actin and the most increased hepatocyte growth factors
      (HGF) and matrix metalloprotease (MMP) two in the livers. In conclusion, PS
      modified NLCs nanoparticles prolonged the retention time of Cur, and enhanced its
      bioavailability and delivery efficiency to the livers, resulting in reduced liver
      fibrosis and up-regulating hepatic expression of HGF and MMP-2.

PMID- 29214889
TI  - Cell-Seeded Adhesive Biomaterial for Repair of Annulus Fibrosus Defects in
      Intervertebral Discs.
AB  - Defects in the annulus fibrosus (AF) of intervertebral discs allow nucleus
      pulposus tissue to herniate causing painful disability. Microdiscectomy
      procedures remove herniated tissue fragments, but unrepaired defects remain
      allowing reherniation or progressive degeneration. Cell therapies show promise to
      enhance repair, but methods are undeveloped and carriers are required to prevent
      cell leakage. To address this challenge, this study developed and evaluated
      genipin-crosslinked fibrin (FibGen) as an adhesive cell carrier optimized for AF
      repair that can deliver cells, match AF material properties, and have low risk of
      extrusion during loading. Part 1 determined that feasibility of bovine AF cells
      encapsulated in high concentration FibGen (F140G6: 140 mg/mL fibrinogen; 6 mg/mL
      genipin) for 7 weeks could maintain high viability, but had little proliferation
      or matrix deposition. Part 2 screened tissue mechanics and in situ failure
      testing of nine FibGen formulations (fibrin: 35-140 mg/mL; genipin: 1-6 mg/mL).
      F140G6 formulation matched AF shear and compressive properties and significantly
      improved failure strength in situ. Formulations with reduced genipin also
      exhibited satisfactory material properties and failure behaviors warranting
      further biological screening. Part 3 screened AF cells encapsulated in four
      FibGen formulations for 1 week and found that reduced genipin concentrations
      increased cell viability and glycosaminoglycan production. F70G1 (70 mg/mL
      fibrinogen; 1 mg/mL genipin) demonstrated balanced biological and biomechanical
      performance warranting further testing. We conclude that FibGen has potential to
      serve as an adhesive cell carrier to repair AF defects with formulations that can
      be tuned to enhance biomechanical and biological performance; future studies are
      required to develop strategies to enhance matrix production.

PMID- 29214891
TI  - Core competencies in clinical neuropsychology training across the world.
AB  - OBJECTIVE: This work aimed to review main competency requirements from training
      models in countries with well-established specialties in clinical neuropsychology
      and to extract core competencies that likely will apply to clinical
      neuropsychologists regardless of regional and cultural context. METHOD: We
      reviewed standards for post-graduate training in clinical neuropsychology from
      countries in Europe, Australia, and North America based on existing literature,
      presentations at international conferences, and from description of the training
      models from national psychological or neuropsychological associations. RESULTS:
      Despite differences, the reviewed models share similar core competencies
      considered necessary for a specialty in clinical neuropsychology: (1) In-depth
      knowledge of general psychology including clinical psychology (post-graduate
      level), ethical, and legal standards. (2) Expert knowledge about clinically
      relevant brain-behavioral relationships. (3) Comprehensive knowledge about, and
      skills in, related clinical disciplines. (4) In-depth knowledge about and skills
      in neuropsychological assessment, including decision-making and diagnostic
      competency according to current classification of diseases. (5) Competencies in
      the area of diversity and culture in relation to clinical neuropsychology. (6)
      Communication competency of neuropsychological findings and test results to
      relevant and diverse audiences. (7) Knowledge about and skills in psychological
      and neuropsychological intervention, including treatment and rehabilitation.
      CONCLUSIONS: All the models have undergone years of development in accordance
      with requirements of national health care systems in different parts of the
      world. Despite differences, the common core competency requirements across
      different regions of the world suggest generalizability of these competencies. We
      hope this summary can be useful as countries with less established
      neuropsychology training programs develop their models.

PMID- 29214892
TI  - Rutin hydrate ameliorates cadmium chloride-induced spatial memory loss and neural
      apoptosis in rats by enhancing levels of acetylcholine, inhibiting JNK and ERK1/2
      activation and activating mTOR signalling.
AB  - This study aimed at studying the potential neuroprotective effect of Rutin
      hydrate (RH) alone or in conjugation with alpha-tocopherol against cadmium
      chloride (CdCl2)-induced neurotoxicity and cognitive impairment in rats and to
      investigate the mechanisms of action. Rats intoxicated with CdCl2 were treated
      with the vehicle, RH, alpha-tocopherol or combined treatment were examined, and
      compared to control rats received vehicle or individual doses of either drug.
      Data confirmed that RH improves spatial memory function by increasing
      acetylcholine availability, boosting endogenous antioxidant potential, activating
      cell survival and inhibiting apoptotic pathways, an effect that is more effective
      when RH was conjugated with alpha-tocopherol. Mechanism of RH action includes
      activation of PP2A mediated inhibiting of ERK1/2 and JNK apoptotic pathways and
      inhibition of PTEN mediated activation of mTOR survival pathway. In conclusion,
      RH affords a potent neuroprotection against CdCl2-induced brain damage and memory
      dysfunction and co-administration of alpha-tocopherol enhances its activity.

PMID- 29214893
TI  - Educational DVD for parents of children with congenital heart disease - a pilot
      study.
AB  - Parental knowledge regarding their child's congenital heart defect (CHD) is
      limited. This study developed and evaluated an interactive DVD that helped
      parents to understand their child's CHD. A DVD describing four cardiac
      abnormalities was created using videos and Adobe Flash. The parents' knowledge
      was assessed via a questionnaire before and after receiving the DVD. A control
      group did not receive the DVD. The DVDs were successfully created and improved
      the parental knowledge of their child's cardiac anomaly. The pilot study suggests
      the need for further development of DVDs to describe additional abnormalities,
      whilst incorporating local management and outcomes.

PMID- 29214890
TI  - Electronic cigarettes: an aid in smoking cessation, or a new health hazard?
AB  - The issue of electronic cigarettes is one of the most controversial topics in
      public health. There is intense debate and dividing opinions about their use
      patterns, health effects and association with smoking. This is expected since
      they were only recently introduced to the market and they refer to a harm
      reduction approach and strategy that is not universally accepted for smoking and
      tobacco use in the public health community. Three main factors determine the
      public health impact of electronic cigarettes: (1) their safety/risk profile,
      both relative to smoking and in absolute terms; (2) their effectiveness for
      smoking reduction and cessation; (3) the patterns of use by different population
      subgroups, especially never-smokers, and adoption of use by youth. This analysis
      presents a brief overview of currently available evidence and gaps in research
      covering these three factors.

PMID- 29214894
TI  - Phenolic content and in vitro antifungal activity of unripe grape extracts from
      agro-industrial wastes.
AB  - The antifungal activity of unripe grape extracts from agro-industrial wastes has
      been evaluated against several strains of Candida spp. and dermatophytes. All the
      extracts tested showed antifungal activity. The geometric mean MIC ranged from
      53.58 to 214.31 MUg/mL for Candida spp. and from 43.54 to 133.02 MUg/mL for
      dermatophytes. The chemical analyses have been carried out using Liquid
      Chromatograph equipped with a DAD and MS detectors. Flavan-3-ols were the main
      metabolites within all samples ranged from 3.3 to 6.8 mg/g fresh weight. For
      Candida spp. highest negative significant correlation has been found between MICs
      and polymeric flavan-3-ols (r = -0.842; p < 0.001) and for dermatophytes between
      MICs and caffeoyl derivatives (r = -0.962; p < 0.01). The results indicate that
      total extracts obtained from unripe grapes, a large source of waste material
      derived from the wine industry, could be used as a cheap source of value-added
      products.

PMID- 29214896
TI  - Outcome evaluation on cochlear implant users with residual hearing.
AB  - OBJECTIVES: The performance outcome with FreedomTM HybridTM versus the CP900
      series sound processor with Hybrid Hearing was investigated. In addition, a
      preliminary evaluation was conducted to consider the feasibility of upgrading
      experienced electric-only cochlear implant (CI) users who had substantial
      residual hearing to Hybrid Hearing. METHODS: This study was a single-centre
      prospective, non-inferiority design with repeated measures conducted at Hannover
      Medical School (MHH). The randomized AABB cross-over design to compensate for
      learning effects included two test groups. Group 1 compared two systems for
      Hybrid Hearing (Freedom Hybrid sound processor versus CP900 series sound
      processor) and Group 2 compared CP900 series sound processor (electric-only)
      versus the CP900 with Hybrid Hearing in experienced CI users who had confirmed
      residual low-frequency hearing. Groups 1 and 2 were composed of different
      participants. RESULTS: Group 1 (n = 24) performance on speech perception tests
      was equivalent or superior with the CP900 series sound processor showing a
      statistically significant mean improvement of 1.87 dB in background noise (P <
      0.001). The mean speech understanding in quiet showed a better performance by 5%
      (P = 0.064) for participants tested with the CP900. The patient-reported outcome
      questionnaire confirmed the beneficial performance with the CP900 series sound
      processor with Hybrid Hearing. The feasibility portion of the study (Group 2, n =
      14) showed an average benefit of 0.54 dB in background noise when using the CP900
      with Hybrid Hearing function versus electric-only stimulation. CONCLUSIONS: The
      outcome presents sufficient evidence to show the effectiveness of the CP900
      series sound processor with Hybrid Hearing over the Freedom Hybrid for
      participants with substantial residual hearing. Positive outcomes were observed
      for improved speech understanding and subjective hearing performance. Further, a
      trend was demonstrated in the data towards better performance with CP900 with
      Hybrid Hearing versus electric-only stimulation. Hybrid Hearing users showed a
      clinically relevant and statistically a significant benefit from the current
      CP900 series sound processor generation supporting its recommendation, on a case
      by-case basis, to current electric-only users. More research is needed to confirm
      these findings.

PMID- 29214897
TI  - SS-31 peptide enables mitochondrial targeting drug delivery: a promising
      therapeutic alteration to prevent hair cell damage from aminoglycosides.
AB  - Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory
      hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a
      key role in that cellular dysfunction for which no proven effective therapies
      against oto-toxicities exist. Therefore, the aim of the present study was to
      develop a new mitochondrial targeting drug delivery system (DDS) that provided
      improved protection from gentamicin. Particularly, SS-31 peptide-conjugated
      geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles were constructed successfully via emulsion-solvent evaporation
      method. The zebrafish lateral line sensory system was used as an in vivo
      evaluating platform to investigate the protective efficiency against gentamicin.
      SS-31 modification significantly reduced the activity of mechanoelectrical
      transduction (MET) channel and gentamicin uptake in zebrafish lateral line hair
      cells. As expected, SS-31 conjugated nanoparticles showed mitochondrial specific
      accumulation in hair cells when compared with unconjugated formulations.
      Furthermore, intracellular SS-31 modified PLGA NPs slightly enhanced
      mitochondrial membrane potential (MMP, DeltaPsim) and then returned to a steady
      state, indicating their effect on the respiratory chain complexes in
      mitochondria. GGA loaded SS-31 conjugated nanoparticles demonstrated the most
      favorable hair cells survivals against gentamicin when compared with unconjugated
      groups whereas blank formulations failed to exhibit potency, indicating that the
      efficiency was attributed to drug delivery of GGA. These results suggest that our
      constructed mitochondria-targeting PLGA based DDS have potential application in
      protecting hair cells from ototoxic agents.

PMID- 29214898
TI  - Bio-width index: a novel biomarker for prognostication of long term outcomes in
      patients with anaemia and heart failure.
AB  - BACKGROUND: The utility of biomarkers for prognostication of long term outcomes
      in patients with anaemia and heart failure(HF) is not well defined. The objective
      of this study was to assess the ability of a novel biomarker, bio-width index
      (BWI),to improve risk stratification in patients with anaemia and acutely
      decompensated heart failure(ADHF), in comparison to conventional markers, B-type
      natriuretic peptide(BNP) and red- cell distribution width(RDW). METHODS: Data
      from 1569 consecutive patients with ADHF treated at a multidisciplinary HF unit
      was analysed in this study. The bio-width index (BWI) was calculated by
      multiplying BNP to RDW and dividing the product by 10 (BWI = BNP x RDW/10). The
      primary outcome was one year all-cause mortality. RESULTS: During follow up
      (median 422 days), subjects with anaemia had significantly higher one year
      mortality (49.6 vs. 30.5%, p < .001). Cox regression analysis revealed that,
      BWI(HR 2.13, 95%CI 2.02-2.24, p = .018) as well as BNP(HR 1.86, 95%CI 1.78-1.94,
      p = .024), and RDW (HR 1.98, 95%CI 1.91-2.05, p = .033) were all independent
      predictors of one year mortality after adjusting for conventional risk factors.
      BWI had a higher discriminative ability compared to BNP(AUC 0.90 vs. 0.75, p <
      .001) and RDW(AUC 0.90 vs. 0.81, p = .012). The patients with higher BWI (
      >1024.9) had a higher one year mortality(85.1 vs. 29.2%, p < .001). In addition,
      BWI significantly improved the net reclassification compared to both BNP(p =
      .002) and RDW(p = .018). CONCLUSIONS: In patients with anaemia and ADHF, bio
      width index is superior to the established biomarkers such as BNP and RDW in
      prognostication of long term mortality.

PMID- 29214900
TI  - Injury-related hospital admission of female firefighters in South Korea.
AB  - PURPOSE: The main objective of this study was to ascertain whether injury-related
      hospital admission in all South Korea female firefighters is greater than that in
      the general population. METHODS: To perform this comparison, the standardized
      admission ratios (SARs) and their 95% confidence intervals (CIs) were calculated
      by person-years and mortality computation software. RESULTS: Compared to the
      general population, the SARs for overall injury (SAR = 1.57, 95% CI [1.24, 1.96])
      and for injury to the lower back (SAR = 2.78, 95% CI [1.81, 4.07]) in the female
      firefighters were significantly higher. The SARs for injury to the knee (SAR =
      2.48, 95% CI [1.18, 4.55]) in emergency medical services (EMS) workers were
      significantly higher than those in the general population. CONCLUSIONS: Our study
      shows that the SARs of overall injury and injury to the lower back in female
      firefighters and knee injury in the EMS were significantly higher than those in
      the general population. Further studies are needed to protect the lower back of
      firefighters and the knees of EMS.

PMID- 29214899
TI  - Paid staff or volunteers - does it make a difference? The impact of staffing on
      child outcomes for children attending community-based programmes in South Africa
      and Malawi.
AB  - BACKGROUND: Globally, and in low and middle income countries (LMIC) specifically,
      there is a critical shortage of workers. The use of volunteers to support such
      care delivery systems has been examined, there is scant literature on the impact
      of volunteers on child outcome in high human immunodeficiency virus (HIV)
      affected communities. OBJECTIVES: To examine the differential impact of paid
      versus volunteer workforce in Community Based Organisations (CBOs) providing care
      to children and families affected by the HIV epidemic in South Africa and Malawi
      on child outcomes over time. METHODS: This study compared child outcomes for 989
      consecutive children attending CBOs (0.7% refusal) at baseline and 854 at follow
      up (86.3% response rate). RESULTS: Children attending CBOs with paid staff had
      higher self-esteem, fewer emotional/behavioural problems and less perceived
      stigma. Likewise, children attending CBOs with paid staff had fewer educational
      risks, and 20 heightened cognitive performance, and the digit-span memory test.
      After controlling for outcome at baseline, gender, age, HIV status, and
      disability, attending a CBO with paid staff remained a significant independent
      predictor of higher self-esteem scores, less perceived stigma, as well as fewer
      educational risks and better performance on the drawing test. We found no
      associations between CBO attendance - paid or volunteer - and children's
      depressive and trauma symptoms. CONCLUSIONS: Our findings show that in order to
      most optimally impact on child outcome 30 community-based workers (CBWs) should
      ideally be paid with trained staff. Specialised input for more severe child
      difficulties is needed.

PMID- 29214904
TI  - Noise-induced hearing loss: what South African mineworkers know.
AB  - PURPOSE: The current study aimed to investigate the knowledge of mineworkers
      regarding noise-induced hearing loss in the South African gold and non-ferrous
      mining subsectors. METHOD: A descriptive research design was adopted. Semi
      structured interviews were conducted with 90 participants who comprised managers,
      supervisors and miners. Data were analysed qualitatively. RESULTS: The majority
      of participants (97%) acknowledged working in a noisy environment and
      demonstrated knowledge of the consequences of this exposure on their hearing
      function. Although all but one participant indicated having known the importance
      of using hearing protection devices (HPDs), less than 50% reported consistent use
      of HPDs. This highlights gaps in education and training, as well as
      implementation monitoring. All participants reported knowledge regarding the
      importance of hearing monitoring, but a lack of understanding of their test
      results. CONCLUSIONS: Current findings contribute towards evidence regarding
      internal barriers to effective application of best practice in hearing
      conservation programmes (HCPs). Findings highlight the important role of
      occupational audiologists in South African mines and the need for individualized
      education during medical surveillance to enhance efficacy of HCPs. Comprehensive
      education and training programmes regarding noise exposure and exposure
      measurements with consistent HPD efficiency assessments are recommendations
      emanating from these findings.

PMID- 29214905
TI  - The jungle book of neuropsychology: Disentangling the influence of feral
      childhood from adult brain injury in order to provide effective rehabilitation.
AB  - BACKGROUND AND AIMS: This article considers the complexities of
      neuropsychological assessment and rehabilitation in brain injury when the client
      is illiterate, is from a foreign culture with English as a second language, and
      reports highly atypical childhood feral experiences prior to injury. METHOD: MC
      was a 63-year-old woman referred for neuropsychological rehabilitation with a
      diagnosis of suspected St Louis encephalitis and global cognitive impairment. In
      formulating her clinical presentation, consideration was given to a reported
      history of feral childhood living with monkeys in the Colombian jungle and
      subsequent physical and emotional abuse. MC participated in comprehensive
      neuropsychological assessment and then targeted rehabilitation. RESULTS:
      Neuroimaging documented relatively focal damage in the right temporal lobe. MC's
      family described her as "the same but worse"; assessment and formulation
      indicated an exacerbation of attentional, pragmatic, arousal and executive
      weaknesses but with new memory and emotion recognition impairments.
      Rehabilitation techniques for communication and executive difficulties were
      successful despite the complexities of the case. CONCLUSIONS: The importance of
      carefully considered assessment and formulation in understanding MC's
      presentation is discussed. To the authors' knowledge, this is the only case of
      neuropsychological assessment and rehabilitation in brain injury involving a
      history of feral childhood.

PMID- 29214907
TI  - The ATTEND trial: An alternative explanation with implications for future
      recovery and rehabilitation clinical trials.
AB  - Over the past decade, ATTEND is one of only a handful of moderate to large-scale
      nonpharmacologic stroke recovery trials with a focus on rehabilitation. While
      unique in some respects, its test of superiority for the experimental
      intervention returned negative/neutral results, with no differences in outcome
      between the experimental intervention and an appropriate control group - a result
      not uncommon to the majority of moderate to large stroke rehabilitation
      intervention trials (i.e. six out of eight conducted in the past decade). The
      authors offer a number of potential explanations for the negative outcome, all of
      which have merit. We choose not to dwell on these possibilities, but rather offer
      a radically different explanation, one which has implications for future
      rehabilitation clinical trials. Our premise is that the process of
      neurorehabilitation is complex and multifaceted, but most importantly, for
      success, it requires a genuine collaboration between the patient and the
      clinician or caregiver to effect optimal recovery. This collaborative
      relationship must be defined by the unique perspective of each patient. By doing
      so, we acknowledge the importance of the individual patient's values, goals,
      perspectives, and capacity. Rehabilitation scientists can design what arguably is
      a scientifically sound intervention that is evidence-based and even with
      preliminary data supporting its efficacy, but if the patient does not value the
      target outcome, does not fully engage in the therapy, or does not expect the
      intervention to succeed, the likelihood of success is poor. We offer this
      opinion, not to be critical, but to suggest a paradigm shift in the way in which
      we conduct stroke recovery and rehabilitation trials.

PMID- 29214906
TI  - Lingua patientis: new words for patient communication and history taking.
AB  - The English language sometimes fails in its ability to describe the severity or
      complexity of medical symptoms and complaints. In frustration, patients (or
      families) occasionally create new words to convey the subtleties of their medical
      history. Although medicine has created a comprehensive technical lexicon for
      physicians, we have failed to develop a corresponding patient-centric vocabulary
      (lingua patientis) that provides more accurate symptom description. The social
      networking of lingua patientis words might enhance history taking and afford
      improved appreciation of disease impact on individual patients. The English
      language is renowned for its capacity for flexibility and adaptability - we need
      to exploit this capacity for the benefit of our patients.

PMID- 29214908
TI  - Prospective memory in first-degree relatives of patients with schizophrenia.
AB  - OBJECTIVES: Among various cognitive impairments in schizophrenia, prospective
      memory (ProM) deficit is unequivocally established. However, there is a paucity
      of research examining whether ProM impairment can be considered a cognitive
      endophenotypic marker in schizophrenia. An important step toward this is to
      assess the status of ProM in first-degree relatives (FDRs) of patients with
      schizophrenia. Keeping this in view, present study has been conducted to assess
      event- and time-based ProM in FDRs of patients with schizophrenia. METHODS:
      Twenty patients with schizophrenia, 20 FDRs of these patients, and 20
      nonpsychiatric (healthy) controls were administered event- and time-based ProM
      tasks. RESULTS: Findings show that the FDRs had poorer performance on event-based
      ProM task in comparison to healthy controls. On time-based task, though the FDRs
      performed poorly in comparison to healthy controls the difference was
      statistically non-significant. The patient group performed poorer than healthy
      controls on both event- and time-based tasks. CONCLUSIONS: Findings of the
      present study indicate that the FDRs of patients with schizophrenia exhibit ProM
      impairment, though to a lesser degree than the patients with schizophrenia.

PMID- 29214913
TI  - In Memoriam.

PMID- 29214909
TI  - Technology-Enhanced Learning Opportunities.

PMID- 29214914
TI  - Folk Healers and Nurse Theorists.

PMID- 29214916
TI  - The Game Is Fair Play: A Kind Reminder to Scientists About Their Role in Keeping
      Science Running.

PMID- 29214917
TI  - Programme potential for the prevention of and response to sexual violence among
      female refugees: a literature review.
AB  - Continuing international conflict has resulted in several million people seeking
      asylum in other countries each year, over half of whom are women. Their reception
      and security in overburdened camps, combined with limited information and
      protection, increases their risk and exposure to sexual violence (SV). This
      literature review explores the opportunities to address SV against female
      refugees, with a particular focus on low-resource settings. A systematic
      literature review of articles published between 2000 and 2016 was conducted
      following PRISMA guidelines. Databases including Medline (Ovid), PubMed, Scopus,
      PsychINFO, CINAHL and the Cochrane Library. Grey literature from key refugee
      websites were searched. Studies were reviewed for quality and analysed according
      to the framework outlined in the UNHCR Guidelines on Prevention and Response of
      Sexual Violence against Refugees. Twenty-nine studies met the inclusion criteria,
      of which 7 studies addressed prevention, 14 studies response and 8 addressed
      both. There are limited numbers of rigorously evaluated SV prevention and
      response interventions available, especially in the context of displacement.
      However, emerging evidence shows that placing a stronger emphasis on programmes
      in the category of engagement/participation and training/education has the
      potential to target underlying causes of SV. SV against female refugees is caused
      by factors including lack of information and gender inequality. This review
      suggests that SV interventions that engage community members in their design and
      delivery, address harmful gender norms through education and advocacy, and
      facilitate strong cooperation between stakeholders, could maximise the efficient
      use of limited resources.

PMID- 29214918
TI  - Effects of knee orthosis adjustment on biomechanical performance and clinical
      outcome in patients with medial knee osteoarthritis.
AB  - BACKGROUND: Valgus bracing in medial knee osteoarthritis aims to improve gait
      function by reducing the loading of the medial compartment. Orthosis composition
      and optimal adjustment is essential to achieve biomechanical and clinical
      effectiveness. OBJECTIVES: To investigate biomechanical functionality during
      gait, pain relief and compliance in patients with knee osteoarthritis using a
      lightweight adjustable knee unloader orthosis. STUDY DESIGN: Prospective
      observational clinical trial. METHODS: Instrumented gait analysis in 22 patients
      with unilateral medial knee osteoarthritis was performed after a 2-week orthosis
      acclimatisation period. Kinematics and kinetics during gait as well as force
      transmission from the orthosis to the knee were analysed. Measurements were
      performed without, at individualised and at reduced orthosis setting. The
      assessment was supplemented by patient-related pain sensation and compliance
      questionnaires. RESULTS: Orthosis wear significantly reduced the knee adduction
      moment by up to 20% depending on orthosis adjustment, whereas pain sensation was
      significantly reduced by 16%. A significant positive correlation was found
      between force transmissions and knee adduction moment as well as for frontal knee
      angle. Compliance was good with a main daily use of 2-6 h. CONCLUSION: The
      orthosis provides significant biomechanical improvements, pain relief and good
      patient compliance. Patients had a biomechanical benefit for the individualised
      and reduced orthosis adjustments. Clinical relevance In patients with medial knee
      osteoarthritis, a lightweight medial unloader orthosis effectively reduced
      external knee adduction moment and pain sensation during daily activities. Thus,
      use of lightweight orthoses effectively supports conservative treatment in medial
      knee osteoarthritis.

PMID- 29214919
TI  - Effect of total-contact orthosis on medial longitudinal arch and lower
      extremities in flexible flatfoot subjects during walking.
AB  - BACKGROUND: Total-contact orthosis (TCO) is one kind of foot orthosis (FO) that
      is used to adjust biomechanics in flexible flatfoot. OBJECTIVE: To determine the
      effects of a TCO on the MLA moment, MLA deformation angle and lower limb
      biomechanics. STUDY DESIGN: Cross-sectional study. METHODS: Seven-flatfoot and
      thirteen-normal foot subjects were recruited by footprint and radiographs. The
      biomechanics of subjects with normal foot (NF), flatfoot with shoe only (FWOT)
      and flatfoot with TCO (FWT) were collected in a 3D motion analysis laboratory and
      force plates. The MLA and lower limb biomechanics in each condition during
      specific sub-phases of stance were analyzed. RESULTS: The NF had larger MLA
      eversion moment after shod walking ( p = 0.001). The FWT condition compared with
      the FWOT condition had a significantly larger peak MLA upward moment ( p = 0.035)
      during pre-swing, larger peak knee external rotation angle ( p = 0.040) during
      mid stance, smaller peak knee extension moment during terminal stance ( p =
      0.035) and a larger ground reaction force in the anterior-posterior direction
      during early stance ( p < 0.05). CONCLUSION: Our study found positive effects
      from the customized TCOs which included an increased TCO angle that led to a
      decreased peak MLA moment in the frontal plane in flexible flatfoot subjects
      during walking. Clinical relevance Lower limb biomechanics is different from
      normal in subjects with flexible flatfoot. The design of a TCO affects MLA, ankle
      and knee biomechanics and may be used to clinically correct biomechanical changes
      in flexible flatfoot.

PMID- 29214920
TI  - Caffeine effects on VO2max test outcomes investigated by a placebo perceived-as
      caffeine design.
AB  - BACKGROUND: Ergogenic effects of caffeine (CAF) ingestion have been observed in
      different cycling exercise modes, and have been associated with alterations in
      ratings of perceived exertion (RPE). However, there has been little investigation
      of maximal oxygen uptake (VO2MAX) test outcomes. AIM: This study aimed to verify
      whether CAF may reduce RPE, thereby improving maximal incremental test (MIT)
      outcomes such as VO2MAX, time to exhaustion and peak power output (WPEAK).
      METHODS: Nine healthy individuals performed three MITs (25 W/min until
      exhaustion) in a random, counterbalanced fashion after ingestion of CAF, placebo
      perceived as caffeine (PLA), and no supplementation (baseline control). VO2 was
      measured throughout the test, while RPE was rated according to overall and leg
      effort sensations. The power output corresponding to submaximal (RPE = 14
      according to the 6-20 Borg scale) and maximal RPE was recorded for both overall
      (O-RPE14 and O-RPEMAX) and leg RPE (L-RPE14 and L-RPEMAX). RESULTS: VO2MAX did
      not change significantly between MITs; however, CAF and PLA increased time to
      exhaustion (? ~18.7% and ~17.1%, respectively; p < .05) and WPEAK (? ~13.0% and
      ~11.8%, respectively; p < .05) when compared with control. When compared with
      control, CAF ingestion reduced submaximal and maximal overall and leg RPEs, the
      effect being greater in maximal (likely beneficial in O-RPEMAX and L-RPEMAX) than
      submaximal RPE (possibly beneficial in O-RPE14 and L-RPE14). Similar results were
      found when participants ingested PLA. CONCLUSIONS: Compared with control, CAF and
      PLA improved MIT performance outcomes such as time to exhaustion and WPEAK,
      without altering VO2MAX values. CAF effects were attributed to placebo.

PMID- 29214921
TI  - Heteropterys tomentosa A. Juss: Toxicological and adaptogenic effects in
      experimental models.
AB  - BACKGROUND: The constant pursuit of improved athletic performance characterizes
      high-performance sport and the use of medicinal plants as dietary supplements is
      becoming widespread among athletes to enhance long-term endurance performance.
      AIM: The present study evaluated the toxicity of Heteropterys tomentosa (HEHt)
      and its acute adaptogenic effects. METHODS: The in vitro safety profile was
      evaluated on CHO-k1 cells using the alamar Blue assay, at concentrations ranging
      from 3.125 to 200 ug/mL. In vivo acute oral toxicity was conducted in male and
      female mice with oral administration of graded doses of HEHt from 400 to 2000
      mg/kg. A subchronic oral toxicity study was completed by oral administration of
      HEHt (50, 200 or 1000 mg/kg) and vehicle for 30 days in male Wistar rats.
      Clinical observations and toxicological related parameters were determined. Blood
      was collected for biochemical and hematological analyses, while histological
      examinations were performed on selected organs. Thereafter, an adaptogenic test
      consisting of progressive loads until exhaustion was conducted in rats ( n =
      5/group) orally pre-treated with the vehicle and HEHt (25, 100 or 400 mg/kg).
      RESULTS: HEHt exhibited no cytotoxic effects on the CHO-k1 cells and, apparently,
      no acute toxicity in mice and no subchronic toxicity in rats. An ergogenic effect
      was observed only at the dose of 25 mg/kg compared with the vehicle in relation
      to time to exhaustion and exercise load ( p = .011 and .019, respectively). HEHt
      is safe at up to 400 mg/kg, contains astilbin and taxifolin as the major
      phytochemical compounds, and exhibited a potential adaptogenic effect.
      CONCLUSIONS: These results justify its anecdotal usage as a tonic, show that the
      hydroethanolic maceration of the root does not cause toxicity, and provide
      scientific evidence of its potential as a source of new adaptogenic substance(s).

PMID- 29214922
TI  - The design and rationale of an interdisciplinary, non-prescriptive, and Health at
      Every Size(r)-based clinical trial: The "Health and Wellness in Obesity" study.
AB  - BACKGROUND: This manuscript describes the design and rationale of a clinical
      trial that aims to investigate the multiple physiological, attitudinal,
      nutritional, and behavioral effects of a new interdisciplinary intervention based
      on the Health at Every Size(r) (HAES(r)) approach in obese women. METHODS: This
      will be a prospective, 7-month, randomized (2:1), mixed-method clinical trial.
      Obese women will be recruited and randomly allocated into two groups. The
      intervention group (I-HAES(r); proposed n = 40) will undertake a novel HAES(r)
      based intervention. Participants will take part in an exercise program, nutrition
      counseling sessions, and philosophical workshops, all aligned with the principles
      of the HAES(r) approach. The control group (CTRL; proposed n = 20) will
      participate in a program using a traditional HAES(r)-based group format,
      characterized by bimonthly lectures about the same topics offered to the
      experimental group, encouraging the adoption of a healthy lifestyle. The
      following multiple quantitative outcomes will be assessed pre and post
      intervention: health-related quality of life, cardiovascular risk factors,
      anthropometric assessments, physical activity level, physical capacity and
      function, and psychological and behavioral assessments. Qualitative analysis will
      be used to evaluate the experiences of the participants throughout the
      intervention, as assessed by focus groups and semi-structured interviews.
      CONCLUSIONS: The interdisciplinary research team leading this study has varied
      and complementary expertise. The knowledge arising from this study will help to
      guide new interdisciplinary interventions with the potential to holistically
      improve the health of obese individuals. This trial is registered at
      Clinicaltrials.gov (NCT02102061).

PMID- 29214923
TI  - Creatine supplementation elicits greater muscle hypertrophy in upper than lower
      limbs and trunk in resistance-trained men.
AB  - BACKGROUND: Creatine (Cr) supplementation associated with resistance training
      produces greater muscular strength improvements in the upper compared with the
      lower body; however, no study has investigated if such region-specific results
      are seen with gains in muscle mass. AIM: We aimed to evaluate the effect of Cr
      supplementation in combination with resistance training on lean soft tissue
      changes in the upper and lower limbs and trunk in resistance-trained young adult
      men. METHODS: In a randomized, double-blind and placebo-controlled design, 43
      resistance-trained men (22.7 +/- 3.0 years, 72.9 +/- 8.7 kg, 177.9 +/- 5.7 cm,
      23.0 +/- 2.5 kg/m2) received either creatine (Cr, n = 22) or placebo (PLA, n =
      21) over an 8-week study period. The supplementation protocol included a loading
      phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks,
      single dose of 0.03 g/kg per day). During the same period, subjects performed
      resistance training four times per week using the following two-way split
      routine: Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday
      and Friday = back, biceps, thighs, and calves. Lean soft tissue of the upper
      limbs (ULLST), lower limbs (LLLST), and trunk (TLST) was assessed by dual-energy
      X-ray absorptiometry before and after the intervention. RESULTS: Both groups
      showed significant ( p < 0.001) improvements in ULLST, LLLST, TLST, and the Cr
      group achieved greater ( p < 0.001) increases in these outcomes compared with
      PLA. For the Cr group, improvements in ULLST (7.1 +/- 2.9%) were higher than
      those observed in LLLST (3.2 +/- 2.1%) and TLST (2.1 +/- 2.2%). Otherwise, for
      PLA group there was no significant difference in the magnitude of segmental
      muscle hypertrophy (ULLST = 1.6 +/- 3.0%; LLLST = 0.7 +/- 2.8%; TLST = 0.7 +/-
      2.8%). CONCLUSION: Our results suggest that Cr supplementation can positively
      augment muscle hypertrophy in resistance-trained young adult men, particularly in
      the upper limbs.

PMID- 29214924
TI  - Different protein and derivatives supplementation strategies combined with
      resistance training in pre-frail and frail elderly: Rationale and protocol for
      the "Pro-Elderly" Study.
AB  - BACKGROUND: Frailty is a multifactorial geriatric syndrome characterized by
      progressive decline in health and associated with decreased muscle mass,
      strength, and functional capacity. Resistance training (RT) combined with protein
      or amino acids supplementation has been shown to be promising for mitigating age
      related impairments. AIM: To investigate the chronic effects of different
      strategies of protein and derivatives supplementation in association with RT on
      selected health-related parameters in pre-frail and frail elderly. METHODS: This
      is a series of double-blind, randomized, placebo-controlled, parallel-group
      clinical trials. Volunteers will be divided into nine groups, comprising four
      different sub-studies evaluating the effects of: isolated leucine supplementation
      (study 1); protein source (whey vs. soy - study 2); combination of whey protein
      and creatine (study 3); and sexual dimorphism on the response to protein intake
      and RT (males vs. females - study 4). Muscle cross-sectional area, fiber cross
      sectional area, body composition, lower-limb maximal dynamic and isometric
      strength, functionality, lipid profile, biochemical parameters, renal function,
      quality of life, and nutritional status will be assessed before and after a 16
      week intervention period. Data will be tested for normality and a mixed-model for
      repeated measures will be conducted to assess within- and between-group effects
      of the intervention on the dependent variables. Confidence intervals (95%),
      effect sizes, and relative changes will also be determined, with significance set
      at p < 0.05.

PMID- 29214925
TI  - Combined exercise training reduces climacteric symptoms without the additive
      effects of isoflavone supplementation: A clinical, controlled, randomised, double
      blind study.
AB  - BACKGROUND: Exercise and supplementation with isoflavones are therapies used to
      prevent and treat climacteric symptoms. AIM: To verify the effects of 10 weeks of
      combined aerobic and resistance training and isoflavone supplementation on
      climacteric symptoms in postmenopausal women. METHODS: A randomised, double
      blind, controlled clinical trial was performed. A total of 32 postmenopausal
      women, aged 54.4 +/- 5.4 years, with a body mass index of 26.6 +/- 3.0 kg/m2 and
      5.6 +/- 4.6 years after menopause, were randomly assigned to groups: placebo and
      exercise (PLA + EXE, n = 15) or 100 mg of isoflavone and exercise (ISO + EXE, n =
      17). At the beginning and after 10 weeks of aerobic + resistance (20 min each,
      moderate intensity) training, climacteric symptoms were evaluated using the Blatt
      Kupperman Menopausal Index, Cervantes Scale and Menopause Rating Scale. ANCOVA
      was used for analysis between groups and at different times, with the covariate
      adjusted by the pre-value. The level of significance considered was p < 0.05.
      RESULTS: A reduction in climacteric symptoms was observed in both groups, without
      differences between the interventions. The reductions were 45% and 50% for the
      Blatt-Kupperman Menopausal Index, 41% and 52% for the MRS and 39% and 39% for the
      Cervantes Scale in the ISO + EXE and PLA + EXE groups, respectively. In the
      descriptive analysis of the Blatt-Kupperman Menopausal Index values, there was an
      increase in the absence of symptoms from 48-77% in the ISO + EXE group and 24-58%
      in the PLA + EXE group. CONCLUSIONS: A period of 10 weeks of combined training
      was effective in improving climacteric symptoms in post-menopausal women.
      However, isoflavone supplementation did not promote additional effects in
      improving symptoms.

PMID- 29214926
TI  - Aerobic training performed at ventilatory threshold improves liver enzymes and
      lipid profile related to non-alcoholic fatty liver disease in adolescents with
      obesity.
AB  - BACKGROUND: Despite the positive effects of high-intensity training on weight
      management and health-related outcomes, it is postulated that high-intensity
      training may also induce oxidative stress, increasing hepatic damage. AIM: The
      aim of this study was to compare the effects of low versus high-intensity
      training on biomarkers related to non-alcoholic fatty liver disease (NAFLD) in
      adolescents with obesity. METHODS: For this study 107 adolescents (15 +/- 1
      years) with obesity (BMI = 34.7 +/- 4.1 kg/m2) were randomized into High
      Intensity Training (HIT, n = 31), Low-Intensity Training (LIT, n = 31) or Control
      Group (CG, n = 45). Adolescents from HIT and LIT received nutritional,
      psychological and clinical counseling. Blood lipids, Castelli risk index,
      glucose, insulin and hepatic enzymes were measured at baseline and after 12
      weeks. RESULTS: Castelli risk index 1 was reduced in all groups ( p < 0.001) with
      moderate effect size ( d) for HIT ( d = 0.62) and LIT ( d = 0.66). Castelli risk
      index 2 also decreased ( p < 0.001 for all groups; HIT d = 0.65; LIT d = 0.79).
      High-density lipoprotein increased in all groups ( d = 0.25 and d = 0.18 in HIT
      and LIT), while alanine aminotransferase tended to reduce ( p = 0.062) in HIT ( d
      = 0.34) and LIT ( d = 0.73) and aspartate aminotransferase decreased ( p = 0.024)
      in both HIT ( d = 0.24) and LIT ( d = 0.45). There were no changes in glucose,
      insulin and insulin resistance. CONCLUSION: Both high and low-intensity training
      improved biomarkers related to NAFLD. Thus, high-intensity training can be a safe
      and effective alternative to prevent and treat NAFLD in adolescents with obesity.

PMID- 29214927
TI  - Probiotic supplementation in sports and physical exercise: Does it present any
      ergogenic effect?
AB  - BACKGROUND: Probiotics are live microorganisms that promote health benefits to
      the host. Evidence indicates that some probiotic strains play an immunomodulatory
      role and reduce the incidence of respiratory and gastrointestinal infections in
      athletes and in physical activity practitioners. For this reason, probiotic
      supplementation could indirectly improve exercise performance. However, recent
      studies have observed direct ergogenic effects of probiotics, but the mechanisms
      of action are poorly elucidated. OBJECTIVE: In this study, we aim to synthesize
      available knowledge on the effect of probiotics on physical exercise, identify
      the mechanisms of action by which probiotics could improve performance directly
      and indirectly, and verify whether probiotics have any ergogenic effect. METHODS:
      The study was performed in the PubMed database in February 2017, without
      limitation as to the publication period. The keyword combinations used were:
      'Probiotics' and 'Sports' ( n = 17 articles), 'Probiotics' and 'Exercise' ( n =
      26 articles) and 'Probiotics' and 'Athletes' ( n = 11 articles). RESULTS: Of the
      16 studies evaluated, only six applied performance tests, of which only two
      demonstrated that probiotic supplementation increases performance, but one of
      them was performed with mice. CONCLUSIONS: According to the studies evaluated,
      probiotic supplementation does not present ergogenic effect, however, considering
      the small number of studies, this subject should be better investigated.

PMID- 29214928
TI  - Editorial.

PMID- 29214930
TI  - ?

PMID- 29214929
TI  - ["For me, Pressure at School is the Most Relevant in my Life" - Empirical Based
      Implications for Life World Orientation in Health Promotion at School].
AB  - "For me, Pressure at School is the Most Relevant in my Life" - Empirical Based
      Implications for Life World Orientation in Health Promotion at School School is a
      key system that supports all processes of adolescent development. Next to
      qualification, as one part of personality development, all developmental tasks of
      adolescence can take place within the school environment, through close
      interplay. This interplay both influences, and is influenced by young people's
      health which is essential to promote adolescent development and foster wellbeing
      in everyday life for young people. On one hand, risk taking behaviour can impact
      health and developmental progress. On the other hand, biopsychosocial changes can
      emerge to challenge young people in terms of coping with life and managing the
      tasks of normal adolescent development. Experiencing ill health can further limit
      young people's access to systems and social interaction essential to promote
      development. In this instance, life world orientation in health promotion becomes
      one fundamental part of social work, especially school social work (Rademaker,
      2017b). In this paper a holistic perspective on health is formulated, as an
      essential part of young people's daily life. The paper specifically focusses on
      social work's potential to empower young people to engage with their available
      resources to promote health related agency. A triangulated study (2013-2015)
      provides an empirical example. Based on a questionnaire with 500 pupils aged 15
      16 years (N = 395), three health types could be identified, a healthy, an
      unhealthy and one in average, and prototypical cases (N = 12) were interviewed in
      focus group discussions. The interplay of resources and structural borders in the
      life world of the participants could be reconstructed to provide understanding of
      how health related agency emerges in the lives of young people and shape their
      option to health.

PMID- 29214931
TI  - [Intervention and Therapy for Perpetrators and Victims of Bullying: A Systematic
      Review].
AB  - Intervention and Therapy for Perpetrators and Victims of Bullying: A Systematic
      Review Bullying is a form of repeated and aggressive behavior with serious
      consequences for victims and perpetrators, who often suffer from their
      experiences long after the bullying episodes have ended. However, the therapeutic
      treatment of bullying and its consequences represents a neglected topic in
      bullying research. Objective of the present article is to review publications
      systematically describing targeted interventions for the treatment of bullying
      (for victims and perpetrators) and associated disorders. The selection process
      consisted of a comprehensive systematic search in national and international
      databases that identified 34 targeted interventions in 31 publications from 14
      different countries. The review of ten interventions featuring a controlled
      design revealed that in particular treatments on both the individual and socio
      ecological level (particularly parents) are effective. The remaining 24
      treatments lack a controlled evaluation. Two thirds of the interventions focus on
      victims. In contrast to the treatment of perpetrators, the emphasis here lies on
      group therapy. Although treatments of bullying apply a range of therapeutic
      approaches and methods, cognitive behavioral therapy is represented most
      prominently. As a conclusion one can observe an existing lack of research in
      evidence-based targeted interventions for the treatment of bullying and its
      consequences for victims and perpetrators. To our knowledge, this is the first
      systematic review of therapeutic interventions for bullying in children and
      adolescents.

PMID- 29214935
TI  - ?

PMID- 29214938
TI  - [Test Reviews].

PMID- 29214932
TI  - [Students Having Parents with Mental Health Issues and Teachers' Mental Health
      Literacy].
AB  - Students Having Parents with Mental Health Issues and Teachers' Mental Health
      Literacy Mental health issues of parents of school children often negatively
      affects the children as well, including their school performance and social
      behavior in the school setting. Teachers are then required to take actions with
      regards to supporting children in their coping with and mastering of their home
      situation and their responds to educational demands. As such, schools' and
      teachers' actions can either support affected children and fulfill a protective
      function or respond inappropriately, with negative impact on the affected
      children. Although the societal discussion about and acceptance of mental
      illnesses have increased in recent years, scientific knowledge on how well
      teachers are prepared for meeting the needs of affected students remains
      insufficient. Therefore, this research study examines teachers' attitudes
      towards, knowledge about, and competencies regarding children affected by a
      mentally ill parent. 15 in-depth interviews and 3 focus groups (n = 11) with
      teachers from primary and secondary schools were conducted and systematically
      analyzed. Although burdens in the family are perceived as major influences on
      children's school day and performance, teachers report to not feel sufficiently
      prepared for and uncertain about supporting and coping with the special needs of
      affected students. Instead they report to "learn from a case to case" basis.
      Recognizing the family situation of children with mentally ill parents is
      reported to be especially difficult for teachers. Responding inadequately and
      insensitive to the needs of affected children was perceived as a serious burden
      for teachers themselves. While schools can function as entry points to
      professional social help systems, teachers frequently reported barriers and
      challenges in accessing, communicating, and collaborating with these systems. The
      practical implications of these results regarding the "Mental Health Literacy" of
      teachers are being discussed.

PMID- 29214939
TI  - ?

PMID- 29214941
TI  - ?

PMID- 29214940
TI  - [School Attendance of Children with Mental Health Problems].
AB  - School Attendance of Children with Mental Health Problems School can support a
      child's resilience as well as be a risk to the child's mental health. However
      school is an indicator of social participation, an aspect that flourished
      especially in the debate about inclusion. In this paper assistance opportunities
      are being discussed that are established to support children with a psychological
      disease in school. Three of the different concepts of funding priorities for
      special educational needs in the German system will be presented:
      "Forderschwerpunkt emotionale und soziale Entwicklung" (special needs in
      emotional and social development), "besonderer Forderbedarf "(special needs) and
      "Schulbegleitung" (school assistants). Also, the conditions for students of
      schools in hospitals and clinics will be analyzed and the reintegration process
      back to home school will be considered. It becomes unequivocal that there is
      little data about special assistance opportunities and that law structures in the
      federal states of Germany differ from each other and are partly unclear. The
      involvement of the three systems school, child and youth welfare service and
      child and youth psychiatry demands solid structures of communication and
      cooperation and a common continuous work across systems' borders during the
      child's school years.

PMID- 29214944
TI  - [News].

PMID- 29214943
TI  - [The authors in this issue].

PMID- 29214945
TI  - [Quality of life and mental health of patients with severe heart failure with or
      without technical support for the left cardiac ventricle - a cross-sectional
      study].
AB  - : Quality of life and mental health of patients with severe heart failure with or
      without technical support for the left cardiac ventricle - a cross-sectional
      study Objectives: Chronic heart failure is associated with reduced quality of
      life (QoL) and poor prognosis. Support via a left ventricular assist device
      (LVAD) is an alternative to optimised medical management for patients with
      advanced heart failure. This study evaluated health-related QoL with both therapy
      options. METHODS: In this consecutive cross-sectional study, patients with LVAD
      support (n = 50) and patients with optimised medical management (n = 50) were
      interviewed comprehensively about various domains of QoL, emotional stress,
      perceived self-efficacy, social support, life satisfaction, and communication.
      RESULTS: LVAD patients had a better overall QoL (KCCQ, clinical summary: MW: 67.4
      vs. 52.9). Patients with medical management reported increased emotional stress
      stemming from depressed mood (HADS-D, MW: 7.1 vs.MW: 6.0). Depressed mood proved
      to be the most significant negative predictor for health-related QoL as well as
      for emotional well-being. CONCLUSIONS: Although they had a worse clinical
      situation preoperatively, LVAD patients had a significantly better QoL in both
      physical dimensions and functional competencies as well as significantly less
      psychological stress through depressed mood and anxiety.

PMID- 29214947
TI  - [Reviewers 2016/2017].

PMID- 29214946
TI  - Psychosomatic and Psychosocial Questions Regarding Bariatric Surgery: What Do We
      Know, or What Do We Think We Know?
AB  - SUBJECT: In view of the epidemic increase in severe obesity and the
      ineffectiveness of conservative weight-loss interventions, bariatric surgery
      delivers compelling results for patients with class II (BMI >= 35 kg/m2) and
      class III obesity (BMI >= 40 kg/m2), not only in reducing weight over the long
      term, but also in reducing obesity-related somatic comorbidity and improving
      psychosocial functioning and quality of life. Investigations into the
      psychosocial aspects of obesity surgery have proliferated over the last 15 years,
      providing a huge amount of essential research data. Yet the results are partly
      contradictory and highly dependent on the duration of follow-up. METHODS: Based
      of a narrative review, this article provides an overview of the current status
      and recent developments of the reciprocal effects between bariatric surgery and
      psychosocial functioning. The review focused on eight domains representing
      important psychosomatic and psychosocial aspects of bariatric surgery. RESULTS:
      Especially in cases of class II and III obesity, bariatric surgery is the only
      means to reduce bodyweight significantly and permanently, though they carry with
      them the associated risk factors of metabolic, cardiovascular, and oncological
      diseases.With regard to psychosocial and psychosomatic aspects, studies with a
      short-term catamnesis (approx. 3 years) speak in favor of an improvement in the
      quality of life including mental disorders. If we consider studies with longer
      follow-ups, however, the results are not as uniform. In particular, we observe an
      increase in harmful alcohol consumption, self-harm behavior, and suicide risk.
      CONCLUSIONS: In light of mental well-being and thus also quality of life,
      bariatric surgery would appear to convey an elevated risk for a minority of
      patients.Yet identifying these patients before surgery has so far been
      insufficient.

PMID- 29214948
TI  - Measuring Self-Soothing Ability in Patients with Childhood Trauma - Psychometric
      Evaluation of the Self-Soothing Scale in a Clinical Sample.
AB  - OBJECTIVES: The regulation of strong emotions is an essential skill for
      traumatized patients. The present instrument was developed for the measurement of
      the self-soothing ability in traumatized patients. METHODS: The psychometric
      properties of the SBS were investigated in a clinical sample of patients with
      childhood trauma (N = 143). In addition, the study explored the factorial
      structure, internal consistency, retest reliability, convergent validity, and
      responsiveness of the instrument. RESULTS: Results of an exploratory factor
      analysis indicated a two-factor structure: 'self-soothing' and 'impulse control',
      explaining 55% of the variance. The total score showed a good internal
      consistency (alpha = .83) and re-test reliability (rtt = .87) as well as good
      validity and responsiveness. CONCLUSIONS: The 7-item SBS is a suitable instrument
      for the measurement of self-soothing ability in traumatized patients.

PMID- 29214950
TI  - [Congress dates].

PMID- 29214949
TI  - [A review on psychosomatic factors affecting the outcome after total knee
      arthroplasty (TKA)].
AB  - : A review on psychosomatic factors affecting the outcome after total knee
      arthroplasty (TKA) Objectives: In today's ageing Western societies, arthroplasty
      is a common treatment for endstage osteoarthritis. Despite highly developed
      implants and surgery, however, this treatment does not always succeed in
      relieving pain and restoring joint function, i.e., in restoring satisfactory
      algofunction. Clinicians partly blame psychological factors for this discrepancy,
      especially in the absence of objective medical complications. METHODS: The
      present review summarizes previous studies on the role of psychosomatic
      interactions affecting the course after total knee arthroplasty (TKA). RESULTS:
      During the perioperative period, patients with TKA suffer from marked psychic
      distress that is also linked to the postoperative algofunction. CONCLUSIONS: We
      discuss the theoretical and clinical implications of the findings reviewed.

PMID- 29214951
TI  - [Looking into international journals].

PMID- 29214952
TI  - [Editorial].

PMID- 29214953
TI  - [Contents].

PMID- 29214954
TI  - ?

PMID- 29214955
TI  - Compulsory Organ Retrieval: Morally, But Not Socially, Justified.
AB  - The number of patients with organ failure who could potentially benefit from
      transplantation continues to exceed the available supply of organs. Despite
      numerous efforts to increase the number of donors, there remains an enormous
      mismatch between demand and supply. Large numbers of people still die with
      potentially transplantable organs remaining in situ, most frequently as a result
      of family objections. I argue that there are no persuasive moral arguments
      against mandated organ retrieval from all dead individuals who meet clinical
      criteria. However, because of continuing endemic prejudice in United States
      society and its healthcare system and the distrust this engenders, I conclude
      that proceeding with a policy of compulsory organ retrieval, even if morally
      unobjectionable, would not be warranted.

PMID- 29214956
TI  - Wickedness, Moral Responsibility, and Access to Transplantable Livers.
AB  - Under the current conditions of scarcity of transplantable livers, difficult
      decisions need to be made about access. There is a growing consensus that it is
      morally justified to give people with ARESLD lower priority than those whose need
      is not self-caused. The purpose of this article is to critically examine the
      conditions under which such prioritization is morally justified, by challenging
      arguments put forth by Walter Glannon and Daniel Brudney. There are serious
      theoretical and practical problems with these views, which have to do with the
      nature and scope of the (putative) moral duty not to contribute to the
      competition for scarce transplantable livers, and the difficulty in determining
      whether people are responsible for their weakness or even wickedness of
      character. These problems need to be resolved if we are to be morally justified
      in determining access based on causal and moral responsibility for being in need.

PMID- 29214958
TI  - From the Editors: Mixing It Up.

PMID- 29214957
TI  - My Path to Bioethics.
AB  - In this series of essays, The Road Less Traveled, noted bioethicists share their
      stories and the personal experiences that prompted them to pursue the field.
      These memoirs are less professional chronologies and more descriptions of the
      seminal touchstone events and turning points that led-often unexpectedly-to their
      career path.

PMID- 29214959
TI  - The Risk in Living Kidney Donation.
AB  - This article examines two questions. (1) If prospective living kidney donors knew
      of the lifetime risk of end-stage renal disease (ESRD) in their remaining kidney,
      then would they be as willing to give it up? and (2) What should transplant
      organizations and physicians be telling those who express an interest in donating
      a kidney about risk? Based on the principle that prospective donors must be fully
      informed of the risk, I raise the issue of a possible obstacle to closing the gap
      between the availability and need of transplantable kidneys. Some strategies are
      offered to address this problem.

PMID- 29214960
TI  - First Come, First Served in the Intensive Care Unit: Always?
AB  - Because the demand for intensive care unit (ICU) beds exceeds the supply in
      general, and because of the formidable costs of that level of care, clinicians
      face ethical issues when rationing this kind of care not only at the point of
      admission to the ICU, but also after the fact. Under what conditions-if any-may
      patients be denied admission to the ICU or removed after admission? One
      professional medical group has defended a rule of "first come, first served" in
      ICU admissions, and this approach has numerous moral considerations in its favor.
      We show, however, that admission to the ICU is not in and of itself guaranteed;
      we also show that as a matter of principle, it can be morally permissible to
      remove certain patients from the ICU, contrary to the idea that because they were
      admitted first, they are entitled to stay indefinitely through the point of
      recovery, death, or voluntary withdrawal. What remains necessary to help guide
      these kinds of decisions is the articulation of clear standards for discontinuing
      intensive care, and the articulation of these standards in a way consistent with
      not only fiduciary and legal duties that attach to clinical care but also with
      democratic decision making processes.

PMID- 29214961
TI  - Microlevel Prioritizations and Incommensurability.
AB  - This article addresses the prioritization questions that arise when people
      attempt to institutionalize reasonable ethical principles and create guidelines
      for microlevel decisions. I propose that this instantiates an incommensurability
      problem, and suggest two different kinds of practical solutions for dealing with
      this issue.

PMID- 29214962
TI  - Prisoners as Living Donors: A Vulnerabilities Analysis.
AB  - Although national guidelines exist for evaluating the eligibility of potential
      living donors and for procuring their informed consent, no special protections or
      considerations exist for potential living donors who are incarcerated. Human
      research subject protections in the United States are codified in the Federal
      Regulations, 45 CFR 46, and special protections are given to prisoners. Living
      donor transplantation has parallels with human subject research in that both
      activities are performed with the primary goal of benefiting third parties. In
      this article, we describe what special considerations should be provided to
      prisoners as potential living donors using a vulnerabilities approach adapted
      from the human research subject protection literature.

PMID- 29214963
TI  - Ideology and Palliative Care: Moral Hazards at the Bedside.
AB  - Palliative care has had a long-standing commitment to teaching medical students
      and other medical professionals about pain management, communication, supporting
      patients in their decisions, and providing compassionate end-of-life care.
      Palliative care programs also have a critical role in helping patients understand
      medical conditions, and in supporting them in dealing with pain, fear of dying,
      and the experiences of the terminal phase of their lives. We applaud their
      efforts to provide that critical training and fully support their continued
      important work in meeting the needs of patients and families. Although we
      appreciate the contributions of palliative care services, we have noted a problem
      involving some palliative care professionals' attitudes, methods of
      decisionmaking, and use of language. In this article we explain these problems by
      discussing two cases that we encountered.

PMID- 29214964
TI  - The Ethics of Making Patients Responsible.
AB  - In their daily clinical work, healthcare professionals generally apply what seems
      to be a double standard for the responsibility of patients. On the one hand,
      patients are encouraged to take responsibility for lifestyle changes that can
      improve their chances of good health. On the other hand, when patients fail to
      follow such recommendations, they are not held responsible for the failure. This
      seeming inconsistency is explained in terms of the distinction between task
      responsibility and blame responsibility. The double standard for responsibility
      is shown to be epistemologically rational, ethically commendable, and
      therapeutically advantageous. However, this non-blaming approach to patient
      responsibility is threatened by proposals to assign lower priority in healthcare
      to patients who are themselves responsible for their disease. Such responsibility
      based priority setting requires that physicians assign blame responsibility to
      their patients, a practice that would run into conflict with the ethical
      foundations of the patient-physician relationship. Therefore, such proposals
      should be rejected.

PMID- 29214965
TI  - Is Paid Surrogacy a Form of Reproductive Prostitution? A Kantian Perspective.
AB  - This article reexamines the "prostitution objection" to paid surrogacy, and
      argues that rebuttals to this objection fail to focus on surrogates as embodied
      persons. This failure is based on the false distinction between "selling one's
      reproductive services" and "selling one's body." To ground the analysis of humans
      as embodied persons, this article uses Kant's late ethical theory, which develops
      the conceptual framework for understanding human beings as embodied selves.
      Literature on surrogacy commonly emphasizes that all Kantian duties heed to the
      categorical prohibition to treat persons as mere means. What this literature
      leaves out is that this imperative commands us more specifically to engage
      ourselves and others as embodied persons. This article aims to relate this point
      to a specific issue in assisted reproduction. It argues that a Kantian account of
      human beings as embodied persons prohibits paid surrogacy on exactly the same
      grounds as it prohibits prostitution.

PMID- 29214966
TI  - Communicating Identifiability Risks to Biobank Donors.
AB  - Recent highly publicized privacy breaches in healthcare and genomics research
      have led many to question whether current standards of data protection are
      adequate. Improvements in de-identification techniques, combined with pervasive
      data sharing, have increased the likelihood that external parties can track
      individuals across multiple databases. This article focuses on the communication
      of identifiability risks in the process of obtaining consent for donation and
      research. Most ethical discussions of identifiability risks have focused on the
      severity of the risk and how it might be mitigated, and what precisely is at
      stake in pervasive data sharing. However, there has been little discussion of
      whether and how to communicate the risk to potential donors. We review the
      ethical arguments behind favoring different types of risk communication in the
      consent process, and outline how identifiability concerns can be incorporated
      into either a detailed or a simplified method of communicating risks during the
      consent process.

PMID- 29214967
TI  - Fear of Life, Fear of Death, and Fear of Causing Death: How Legislative Changes
      on Assisted Dying Are Doomed to Fail.
AB  - Fear of life, fear of death, and fear of causing death form a combination that
      prevents reasoned changes in laws concerning end-of-life situations. This is
      shown systematically in this article using the methods of conceptual analysis.
      Prevalent fears are explicated and interpreted to see how their meanings differ
      depending on the chosen normative stance. When the meanings have been clarified,
      the impact of the fears on the motivations and justifications of potential
      legislative reforms are assessed. Two main normative stances are evoked. The
      first makes an appeal to individual self-determination, or autonomy, and the
      second to the traditional professional ethics of physicians. These views partly
      share qualifying elements, including incurability and irreversibility of the
      patient's medical condition, proximity of death, the unbearable nature of
      suffering, and issues of voluntariness further shade the matter. The conclusion
      is that although many motives to change end-of-life laws are admirable, they are
      partly contradictory, as are calls for autonomy and appeals to professional
      ethics; to a degree that good, principled legislative solutions remain improbable
      in the foreseeable future.

PMID- 29214968
TI  - The Therapeutic "Mis"conception: An Examination of its Normative Assumptions and
      a Call for its Revision.
AB  - Dissecting Bioethics, edited by Tuija Takala and Matti Hayry, welcomes
      contributions on the conceptual and theoretical dimensions of bioethics. The
      department is dedicated to the idea that words defined by bioethicists and others
      should not be allowed to imprison people's actual concerns, emotions, and
      thoughts. Papers that expose the many meanings of a concept, describe the
      different readings of a moral doctrine, or provide an alternative angle to
      seemingly self-evident issues are particularly appreciated. To submit a paper or
      to discuss a suitable topic, contact Tuija Takala at tuija.takala@helsinki.fi.

PMID- 29214969
TI  - Pedaling Toward Revelation: My Summer with Flannery O'Connor.
AB  - This section features original work on pathographies-i.e., (auto)biographical
      accounts of disease, illness, and disability-that provide narrative inquiry
      relating to the personal, existential, psychological, social, cultural,
      spiritual, political, and moral meanings of individual experience. Editors are:
      Nathan Carlin and Therese Jones. For submissions, contact Nathan Carlin at:
      Nathan.Carlin@uth.tmc.edu.

PMID- 29214970
TI  - Comparative typing analyses of clinical and environmental strains of the
      Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast.
AB  - PURPOSE: The aim of this study was to assess the biotope of the Cryptococcus
      neoformans/Cryptococcus gattii species complex from Ivory Coast, and clarify the
      possible epidemiological relationship between environmental and clinical strains.
      METHODOLOGY: Samples from Eucalyptus camaldulensis (n=136), Mangifera indica
      (n=13) and pigeon droppings (n=518) were collected from different sites close to
      the living environment of Ivorian HIV patients with cryptococcosis (n=10, 50
      clinical strains). Clinical and environmental strains were characterized by
      molecular serotyping and genotyping [RFLP analysis of the URA5 gene, (GACA)4,
      (GTG)5 and M13 PCR fingerprinting] and compared.Results/Key findings.
      Environmental strains were recovered only from the pigeon droppings. In vitro
      susceptibility profiles showed that all strains were susceptible to fluconazole,
      flucytosine and amphotericin B. All environmental strains consisted of C.
      neoformans (A, AFLP1/VNI), whereas clinical strains included C. neoformans (A,
      AFLP1/VNI), C. neoformans x Cryptococcus deneoformans hybrids (AD, AFLP3/VNIII)
      and Cryptococcus deuterogattii (B, AFLP6/VGII). Two patients were co-infected
      with both C. neoformans and C. neoformans x C. deneoformans hybrids. We noticed a
      low genetic diversity among the environmental samples compared to the high
      diversity of the clinical samples. Some clinical strains were genetically more
      similar to environmental strains than to other clinical strains, including those
      from the same patient. CONCLUSION: These results provide new information on the
      ecology and epidemiology of the C. neoformans/C. gattii species complex in Ivory
      Coast.

PMID- 29214971
TI  - Corrigendum: Evidence for immune activation in patients with residual hepatitis C
      virus RNA long after successful treatment with IFN and ribavirin.

PMID- 29214972
TI  - ICTV Virus Taxonomy Profile: Partitiviridae.
AB  - The Partitiviridae is a family of small, isometric, non-enveloped viruses with
      bisegmented double-stranded (ds) RNA genomes of 3-4.8 kbp. The two genome
      segments are individually encapsidated. The family has five genera, with
      characteristic hosts for members of each genus: either plants or fungi for genera
      Alphapartitivirus and Betapartitivirus, fungi for genus Gammapartitivirus, plants
      for genus Deltapartitivirus and protozoa for genus Cryspovirus. Partitiviruses
      are transmitted intracellularly via seeds (plants), oocysts (protozoa) or hyphal
      anastomosis, cell division and sporogenesis (fungi); there are no known natural
      vectors. This is a summary of the International Committee on Taxonomy of Viruses
      (ICTV) Report on the taxonomy of the Partitiviridae, which is available at
      www.ictv.global/report/partitiviridae.

PMID- 29214973
TI  - Expression of the small regulatory RNA gene mmgR is regulated negatively by AniA
      and positively by NtrC in Sinorhizobium meliloti 2011.
AB  - In the N2-fixing symbiont of alfalfa root nodules, Sinorhizobium meliloti 2011,
      the mmgR gene encodes a 77 nt small untranslated RNA (sRNA) that negatively
      regulates the accumulation of polyhydroxybutyrate (PHB) when the bacterium is
      grown under conditions of surplus carbon (C) in relation to nitrogen (N). We
      previously showed that the expression of mmgR is primarily controlled at the
      transcriptional level and that it depends on the cellular N status, although the
      regulatory mechanism and the factors involved were unknown. In this study, we
      provide experimental data supporting that: (a) mmgR is induced upon N limitation
      with the maximum expression found at the highest tested C/N molar ratio in the
      growth medium; (b) a conserved heptamer TTGTGCA located between the -35 and -10
      mmgR promoter elements is necessary and sufficient for induction by N limitation;
      (c) induction of mmgR requires the N-status regulator NtrC; (d) under C
      limitation, mmgR transcription is repressed by AniA, a global regulator of C
      flow; (e) the mmgR promoter contains a conserved dyadic motif (TGC[N3]GCA)
      partially overlapping the heptamer TTGTGCA, which was also found in the promoters
      of the PHB-related genes phaP1, phaP2, phaZ and phaR (aniA) of S. meliloti and
      other alpha-proteobacteria. Taken together, these results suggest that the mmgR
      promoter would integrate signals from the metabolism of C and N through - at
      least - the global regulators NtrC and AniA, to provide an optimal level of the
      MmgR sRNA to fine-tune gene expression post-transcriptionally according to
      varying C and N availability.

PMID- 29214974
TI  - Insights into the candidacidal mechanism of Ctn[15-34] - a carboxyl-terminal,
      crotalicidin-derived peptide related to cathelicidins.
AB  - PURPOSE: Ctn[15-34], a carboxyl-terminal fragment of crotalicidin (a cathelicidin
      from the venom gland of a South American rattlesnake), has shown antifungal
      activity against clinical and standard strains of Candida species. The aim of the
      present work was to investigate the underlying mechanisms of the candidicidal
      activity of Ctn[15-34]. METHODOLOGY: The time-kill profile and drug synergism
      were evaluated by means of a microdilution assay and multi-parametric flow
      cytometry. The presumptive interaction of Ctn[15-34] with lipid membranes was
      estimated in vitro with a lipid-mimic compound, the chromogenic substance 4-nitro
      3-(octanoyloxy)benzoic acid (4N3OBA).Results/Key findings. The absorbance
      increment (at 425 nm) indicated a concentration- and time-dependent in-solution
      association between Ctn[15-34] and 4N3OBA. The interaction of Ctn[15-34] with
      Candida cells was confirmed by flow cytometric measurements with the 5(6)
      carboxyfluorescein-labelled peptide (CF-Ctn[15-34]). Analysis of the killing time
      of Candida exposed to Ctn[15-34] and amphotericin B (AMB) showed that both the
      peptide and polyene drug reduce the number of c.f.u. but in mechanistically
      different ways. The Ctn[15-34] peptide alone caused yeast cell membrane
      disruption, which was confirmed by lactate dehydrogenase leakage and biomarkers
      of cell death mediated by necrosis. CONCLUSION: Overall, Ctn[15-34] displays a
      synergistic antifungal activity with AMB, an effect that can be further developed
      into a multi-target therapeutic option with other antimycotics currently in use.

PMID- 29214976
TI  - Stray cats are more frequently infected with zoonotic protists than pet cats.
AB  - Faecal samples were collected from cats kept as pets (n = 120) and stray cats (n
      = 135) in Central Europe (Czech Republic, Poland and Slovakia) and screened for
      the presence of Cryptosporidium spp., Giardia intestinalis (Kunstler, 1882),
      Encephalitozoon spp. and Enterocytozoon bieneusi Desportes, Le Charpentier,
      Galian, Bernard, Cochand-Priollet, Lavergne, Ravisse et Modigliani, 1985 by PCR
      analysis of the small-subunit of rRNA (Cryptosporidium spp. and G. intestinalis)
      and ITS (microsporidia) genes. Sequence analysis of targeted genes revealed the
      presence of C. felis Iseki, 1979, G. intestinalis assemblage F, E. cuniculi
      Levaditi, Nicolau et Schoen, 1923 genotype II, and E. bieneusi genotype D. There
      was no correlation between the occurrence of detected parasites and sex, presence
      of diarrhoea or drug treatment (drug containing pyrantel and praziquantel).
      Compared to pet cats (7%), stray cats (30%) were statistically more frequently
      infected with protist parasites and overall may present a greater risk to human
      health.

PMID- 29214975
TI  - Home-based health promotion for older people with mild frailty: the HomeHealth
      intervention development and feasibility RCT.
AB  - BACKGROUND: Mild frailty or pre-frailty is common and yet is potentially
      reversible. Preventing progression to worsening frailty may benefit individuals
      and lower health/social care costs. However, we know little about effective
      approaches to preventing frailty progression. OBJECTIVES: (1) To develop an
      evidence- and theory-based home-based health promotion intervention for older
      people with mild frailty. (2) To assess feasibility, costs and acceptability of
      (i) the intervention and (ii) a full-scale clinical effectiveness and cost
      effectiveness randomised controlled trial (RCT). DESIGN: Evidence reviews,
      qualitative studies, intervention development and a feasibility RCT with process
      evaluation. INTERVENTION DEVELOPMENT: Two systematic reviews (including
      systematic searches of 14 databases and registries, 1990-2016 and 1980-2014), a
      state-of-the-art review (from inception to 2015) and policy review identified
      effective components for our intervention. We collected data on health priorities
      and potential intervention components from semistructured interviews and focus
      groups with older people (aged 65-94 years) (n = 44), carers (n = 12) and
      health/social care professionals (n = 27). These data, and our evidence reviews,
      fed into development of the 'HomeHealth' intervention in collaboration with older
      people and multidisciplinary stakeholders. 'HomeHealth' comprised 3-6 sessions
      with a support worker trained in behaviour change techniques, communication
      skills, exercise, nutrition and mood. Participants addressed self-directed
      independence and well-being goals, supported through education, skills training,
      enabling individuals to overcome barriers, providing feedback, maximising
      motivation and promoting habit formation. FEASIBILITY RCT: Single-blind RCT,
      individually randomised to 'HomeHealth' or treatment as usual (TAU). SETTING:
      Community settings in London and Hertfordshire, UK. PARTICIPANTS: A total of 51
      community-dwelling adults aged >= 65 years with mild frailty. MAIN OUTCOME
      MEASURES: Feasibility - recruitment, retention, acceptability and intervention
      costs. Clinical and health economic outcome data at 6 months included
      functioning, frailty status, well-being, psychological distress, quality of life,
      capability and NHS and societal service utilisation/costs. RESULTS: We
      successfully recruited to target, with good 6-month retention (94%). Trial
      procedures were acceptable with minimal missing data. Individual randomisation
      was feasible. The intervention was acceptable, with good fidelity and modest
      delivery costs (L307 per patient). A total of 96% of participants identified at
      least one goal, which were mostly exercise related (73%). We found significantly
      better functioning (Barthel Index +1.68; p = 0.004), better grip strength (+6.48
      kg; p = 0.02), reduced psychological distress (12-item General Health
      Questionnaire -3.92; p = 0.01) and increased capability-adjusted life-years
      [+0.017; 95% confidence interval (CI) 0.001 to 0.031] at 6 months in the
      intervention arm than the TAU arm, with no differences in other outcomes. NHS and
      carer support costs were variable but, overall, were lower in the intervention
      arm than the TAU arm. The main limitation was difficulty maintaining outcome
      assessor blinding. CONCLUSIONS: Evidence is lacking to inform frailty prevention
      service design, with no large-scale trials of multidomain interventions. From
      stakeholder/public perspectives, new frailty prevention services should be
      personalised and encompass multiple domains, particularly socialising and
      mobility, and can be delivered by trained non-specialists. Our multicomponent
      health promotion intervention was acceptable and delivered at modest cost. Our
      small study shows promise for improving clinical outcomes, including functioning
      and independence. A full-scale individually RCT is feasible. FUTURE WORK: A
      large, definitive RCT of the HomeHealth service is warranted. STUDY REGISTRATION:
      This study is registered as PROSPERO CRD42014010370 and Current Controlled Trials
      ISRCTN11986672. FUNDING: This project was funded by the National Institute for
      Health Research (NIHR) Health Technology Assessment programme and will be
      published in full in Health Technology Assessment; Vol. 21, No. 73. See the NIHR
      Journals Library website for further project information.

PMID- 29214977
TI  - Monte Carlo simulation investigation on the minitype reference radiation employed
      for the calibration of gamma ray dose or dose rate meters.
AB  - Minitype reference radiation (MRR) based on a cesium-137 (Cs-137) isotope
      radioactive source is a core component for carrying out field calibration on
      gamma ray dose or dose rate meters. To explore the source of scattering rays in
      the MRR, and their influence on dose field distribution, we calculated the
      radiation field of the MRR with different shielding wall materials, different
      sizes of shielding boxes, and different detectors. The investigation results
      provide theoretical and technical support for better understanding the MRR, and
      for developing field calibration technologies.

PMID- 29214978
TI  - Characterization of dynamic changes of current source localization based on
      spatiotemporal fMRI constrained EEG source imaging.
AB  - OBJECTIVE: Neuroimaging has been employed as a promising approach to advance our
      understanding of brain networks in both basic and clinical neuroscience.
      Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI)
      represent two neuroimaging modalities with complementary features; EEG has high
      temporal resolution and low spatial resolution while fMRI has high spatial
      resolution and low temporal resolution. Multimodal EEG inverse methods have
      attempted to capitalize on these properties but have been subjected to
      localization error. The dynamic brain transition network (DBTN) approach, a
      spatiotemporal fMRI constrained EEG source imaging method, has recently been
      developed to address these issues by solving the EEG inverse problem in a
      Bayesian framework, utilizing fMRI priors in a spatial and temporal variant
      manner. This paper presents a computer simulation study to provide a detailed
      characterization of the spatial and temporal accuracy of the DBTN method.
      APPROACH: Synthetic EEG data were generated in a series of computer simulations,
      designed to represent realistic and complex brain activity at superficial and
      deep sources with highly dynamical activity time-courses. The source
      reconstruction performance of the DBTN method was tested against the fMRI
      constrained minimum norm estimates algorithm (fMRIMNE). The performances of the
      two inverse methods were evaluated both in terms of spatial and temporal
      accuracy. MAIN RESULTS: In comparison with the commonly used fMRIMNE method,
      results showed that the DBTN method produces results with increased spatial and
      temporal accuracy. The DBTN method also demonstrated the capability to reduce
      crosstalk in the reconstructed cortical time-course(s) induced by neighboring
      regions, mitigate depth bias and improve overall localization accuracy.
      SIGNIFICANCE: The improved spatiotemporal accuracy of the reconstruction allows
      for an improved characterization of complex neural activity. This improvement can
      be extended to any subsequent brain connectivity analyses used to construct the
      associated dynamic brain networks.

PMID- 29214979
TI  - Angular-dependent magnetoresistance study in Ca0.73La0.27FeAs2: a 'parent'
      compound of 112-type iron pnictide superconductors.
AB  - We report a study of angular-dependent magnetoresistance (AMR) with the magnetic
      field rotated in the plane perpendicular to the current on a Ca0.73La0.27FeAs2
      single crystal, which is regarded as a 'parent' compound of 112-type iron
      pnictide superconductors. A pronounced AMR with twofold symmetry is observed,
      signifying the highly anisotropic Fermi surface. By further analyzing the AMR
      data, we find that the Fermi surface above the structural/antiferromagnetic (AFM)
      transition (T s/T N) is quasi-two-dimensional (quasi-2D), as revealed by the 2D
      scaling behavior of the AMR, Deltarho/rho(0) (H, theta)  =  Deltarho/rho(0) (u 0
      Hcostheta), theta being the magnetic field angle with respect to the c axis.
      While such 2D scaling becomes invalid at temperatures below T s/T N, the three
      dimensional (3D) scaling approach by inclusion of the anisotropy of the Fermi
      surface is efficient, indicating that the appearance of the 3D Fermi surface
      contributes to anisotropic electronic transport. Compared with other experimental
      observations, we suspect that the additional 3D hole pocket (generated by the Ca
      d orbital and As1 p z orbital) around the Gamma point in CaFeAs2 will disappear
      in the heavily electron doped regime, and moreover, the Fermi surface should be
      reconstructed across the structural/AFM transition. Besides, a quasi-linear in
      plane magnetoresistance with H//ab is observed at low temperatures and its
      possible origins are also discussed. Our results provide more information to
      further understand the electronic structure of 112-type IBSs.

PMID- 29214980
TI  - Ion chambers compliance results of Brazilian radiation therapy facilities.
AB  - The Brazilian Nuclear Energy Commission (cnen) has been making a constant effort
      to keep up to date with international standards and national needs to strengthen
      the status of radiological protection of the country. The guidelines related to
      radiation therapy facilities have been revised in the last five years in order to
      take into consideration the most relevant aspects of the growing technology as
      well as to mitigate the accidents or incidents observed in practice. Hence,
      clinical dosimeters have gained special importance in this matter. In the present
      work, we discuss the effectiveness of regulation and inspections to the
      enforcement of instrument calibration accuracy for the improvement of patient
      dosimetry and quality control. As a result, we observed that the number of
      calibrated instruments, mainly well chambers, is increasing each year. The same
      behavior is observed for instruments employed in technologically advanced
      radiation treatments such as intensity modulated radiotherapy, volumetric therapy
      and stereotatic radiosurgery. We ascribe this behavior to the new regulation.

PMID- 29214981
TI  - A review on photocatalytic CO2 reduction using perovskite oxide nanomaterials.
AB  - As the search for efficient catalysts for CO2 photoreduction continues,
      nanostructured perovskite oxides have emerged as a class of high-performance
      photocatalytic materials. The perovskite oxide candidates for CO2 photoreduction
      are primarily nanostructured forms of titanates, niobates, tantalates and
      cobaltates. These materials form the focus of this review article because they
      are much sought-after due to their nontoxic nature, adequate chemical stability,
      and tunable crystal structures, bandgaps and surface energies. As compared to
      conventional semiconductors and nanomaterial catalysts, nanostructured perovskite
      oxides also exhibit an extended optical-absorption edge, longer charge carrier
      lifetimes, and favorable band-alignment with respect to reduction potential of
      activated CO2 and reduction products of the same. While CO2 reduction product
      yields of several hundred MUmol-1 h-1 are observed with many types of perovskite
      oxide nanomaterials in stand-alone forms, yield of such quantities are not common
      with semiconductor nanomaterials of other types. In this review, we present
      current state-of-the-art synthesis methods to form perovskite oxide
      nanomaterials, and procedures to engineer their bandgaps. This review also
      presents a comprehensive summary and discussion on crystal structures, defect
      distribution, morphologies and electronic properties of the perovskite oxides,
      and correlation of these properties to CO2 photoreduction performance. This
      review offers researchers key insights for developing advanced perovskite oxides
      in order to further improve the yields of CO2 reduction products.

PMID- 29214982
TI  - Perspectives on theory at the interface of physics and biology.
AB  - Theoretical physics is the search for simple and universal mathematical
      descriptions of the natural world. In contrast, much of modern biology is an
      exploration of the complexity and diversity of life. For many, this contrast is
      prima facie evidence that theory, in the sense that physicists use the word, is
      impossible in a biological context. For others, this contrast serves to highlight
      a grand challenge. I am an optimist, and believe (along with many colleagues)
      that the time is ripe for the emergence of a more unified theoretical physics of
      biological systems, building on successes in thinking about particular phenomena.
      In this essay I try to explain the reasons for my optimism, through a combination
      of historical and modern examples.

PMID- 29214983
TI  - Insight on agglomerates of gold nanoparticles in glass based on surface plasmon
      resonance spectrum: study by multi-spheres T-matrix method.
AB  - The formation of a localized surface plasmon resonance (SPR) spectrum of randomly
      distributed gold nanoparticles in the surface layer of silicate float glass,
      generated and implanted by UV ArF-excimer laser irradiation of a thin gold layer
      sputter-coated on the glass surface, was studied by the T-matrix method, which
      enables particle agglomeration to be taken into account. The experimental
      technique used is promising for the production of submicron patterns of plasmonic
      nanoparticles (given by laser masks or gratings) without damage to the glass
      surface. Analysis of the applicability of the multi-spheres T-matrix (MSTM)
      method to the studied material was performed through calculations of SPR
      characteristics for differently arranged and structured gold nanoparticles (gold
      nanoparticles in solution, particles pairs, and core-shell silver-gold
      nanoparticles) for which either experimental data or results of the modeling by
      other methods are available. For the studied gold nanoparticles in glass, it was
      revealed that the theoretical description of their SPR spectrum requires
      consideration of the plasmon coupling between particles, which can be done
      effectively by MSTM calculations. The obtained statistical distributions over
      particle sizes and over interparticle distances demonstrated the saturation
      behavior with respect to the number of particles under consideration, which
      enabled us to determine the effective aggregate of particles, sufficient to form
      the SPR spectrum. The suggested technique for the fitting of an experimental SPR
      spectrum of gold nanoparticles in glass by varying the geometrical parameters of
      the particles aggregate in the recurring calculations of spectrum by MSTM method
      enabled us to determine statistical characteristics of the aggregate: the average
      distance between particles, average size, and size distribution of the particles.
      The fitting strategy of the SPR spectrum presented here can be applied to
      nanoparticles of any nature and in various substances, and, in principle, can be
      extended for particles with non-spherical shapes, like ellipsoids, rod-like and
      other T-matrix-solvable shapes.

PMID- 29214984
TI  - Electron beam collimation with a photon MLC for standard electron treatments.
AB  - Standard electron treatments are currently still performed using standard or
      molded patient-specific cut-outs placed in the electron applicator. Replacing cut
      outs and electron applicators with a photon multileaf collimator (pMLC) for
      electron beam collimation would make standard electron treatments more efficient
      and would facilitate advanced treatment techniques like modulated electron
      radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple
      source Monte Carlo beam model for pMLC shaped electron beams commissioned at a
      source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm
      and validated for several Varian treatment units with field sizes typically used
      for standard electron treatments. Measurements and dose calculations agree
      generally within 3% of the maximal dose or 2 mm distance to agreement. To
      evaluate the dosimetric consequences of using pMLC collimated electron beams for
      standard electron treatments, pMLC-based and cut-out-based treatment plans are
      created for a left and a right breast boost, a sternum, a testis and a parotid
      gland case. The treatment plans consist of a single electron field, either alone
      (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For
      each case, a pMLC plan with similar treatment plan quality in terms of dose
      homogeneity to the target and absolute mean dose values to the organs at risk
      (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is
      slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR
      is located laterally close to the target with respect to beam direction, or if a
      6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans
      using cut-out collimation can be replaced by plans of similar treatment plan
      quality using pMLC collimation with accurately calculated dose distributions.

PMID- 29214985
TI  - Non-invasive peripheral nerve stimulation via focused ultrasound in vivo.
AB  - Focused ultrasound (FUS) has been employed on a wide range of clinical
      applications to safely and non-invasively achieve desired effects that have
      previously required invasive and lengthy procedures with conventional methods.
      Conventional electrical neuromodulation therapies that are applied to the
      peripheral nervous system (PNS) are invasive and/or non-specific. Recently,
      focused ultrasound has demonstrated the ability to modulate the central nervous
      system and ex vivo peripheral neurons. Here, for the first time, noninvasive
      stimulation of the sciatic nerve eliciting a physiological response in vivo is
      demonstrated with FUS. FUS was applied on the sciatic nerve in mice with
      simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals
      were detected during or directly after ultrasound stimulation along with
      observable muscle contraction of the hind limb. Transecting the sciatic nerve
      downstream of FUS stimulation eliminated EMG activity during FUS stimulation.
      Peak-to-peak EMG response amplitudes and latency were found to be comparable to
      conventional electrical stimulation methods. Histology along with behavioral and
      thermal testing did not indicate damage to the nerve or surrounding regions. The
      findings presented herein demonstrate that FUS can serve as a targeted, safe and
      non-invasive alternative to conventional peripheral nervous system stimulation to
      treat peripheral neuropathic diseases in the clinic.

PMID- 29214986
TI  - Antibiotic resistance in Enterobacter cloacae strains with derepressed/partly
      derepressed/inducible AmpC and extendedspectrum beta-lactamases in Zenica-Doboj
      Canton, Bosnia and Herzegovina.
AB  - Aim To investigate the prevalence of derepressed/partly derepressed/inducible and
      ESBL/AmpC-producing Enterobacter cloacae isolates and treatment options for
      infections associated with those isolates. Methods Antibiotic susceptibility was
      determined by disc diffusion and broth microdilution according to CLSI
      guidelines. Doubledisk synergy test (DDST) was performed in order to screen for
      ESBLs and combined disk test with phenylboronic acid to detect AmpC beta 
      lactamases. PCR was used to detect blaESBL/blacarb genes. Genetic relatedness of
      the strains was determined by pulsed-fieldgel-electrophoresis (PFGE). Results
      Among 14 isolates with the ESBL positive E. cloaceae producing isolates, four
      (28.6%), nine (64.3%) and one (7.1%) isolates were derepressed/partly derepressed
      and inducible AmpC producers. Eleven (out of 14) isolates were resistant to
      cefotaxime, ceftazidime, ceftriaxone, aminoglycosides and fluoroquinolones. All
      isolates were susceptible to imipenem and meropenem, 79% to cefepime. Five (out
      of 14; 35.7%) isolates (four derepressed and one inducible AmpC carrying E.
      cloaceae) were negative in phenotypic test for ESBLs, but positive for broad
      spectrum TEM-1 beta-lactamase. One (out of four derepressed) also produced CMY-2
      beta-lactamase. Four (out of nine) partly derepressed isolates were positive with
      the DDST, but did not yield PCR products with primers targeting TEM, SHV and CTX
      M beta-lactamases. Four positive partly derepressed isolates carried a blaCTX-M-1
      gene, two blaOXA-1 one blaCTX-M-15, OXA-1 and one blaCTX-M-28, OXA-1 (n=1).
      Conclusion Microbiology laboratories must be able to detect and recognize AmpC
      carrying isolates in a timely manner, especially those that are falsely
      susceptible in vitro to drugs that may be consideredfor therapy of infected
      patients.

PMID- 29214987
TI  - Influence of C-reactive protein on the occurrence and assessing of albuminuria
      severity in diabetics.
AB  - Aim To asses relation of serum high sensitive C-reactive protein (hsCRP) level
      with albumin concentration in daily urine in patients with diabetes mellitus type
      2 (T2DM). Methods The prospective study included 69 patients with T2DM, both
      sexes (24 males, 45 females), aged 30-82 years. They were divided into two
      groups: patients with T2DM and normoalbuminuria(T2DM-NA; n=40) and patients with
      T2DM and microalbuminuria (T2DM-MA; n=29). Patients were hospitalized at the
      Department of Internal Medicine, Cantonal Hospital Zenica, in the period January
      April 2014. Immunonephelometry measurement of hsCRP was performed on the
      Nephelometer Analyzer BN II (Siemens, Germany). Results Frequency of patients in
      T2DM-NA and T2DM-MA groups was not significantly different in relation to sex and
      age. There was significant difference in relation to duration of diabetes (
      p=0.001). Average glucose and HbA1c levels were significantly higher in T2DM-NA
      group comparing to T2DM-MA group (p=0.008 and p=0.047, respectively). Serum
      creatinine (p=0.011),urea (p=0.009) and hsCRP (p=0.005) were significantly higher
      in T2DM-MA group compared to T2DM-NA group. Urinary albumin showed significantly
      positive correlation with the hsCRP (rho=0.286; p=0.017), urea (rho=0.503) and
      creatinine (rho=0.438) (p < 0.0005). A one unit (mg/L) increase in hsCRP
      concentration was associated with 11.5% increase of odds of microalbuminuria
      OR=1.115; 95% CI 1.014-1.225; p=0.025). Conclusion Significantly higher values of
      serum hsCRP in patients with type 2 diabetes mellitus and microalbuminuria in
      comparison to those with normoalbuminuria as well as the correlation of values of
      inflammatory marker with urinary albumin implicate a low grade inflammation in
      the progression of diabetic nephropathy.

PMID- 29214988
TI  - Anthropometric characteristics and traffic accident circumstances of patients
      with isolated whiplash injury in University Clinical Hospital Mostar.
AB  - Aim To investigate anthropometric characteristics and traffic accident
      circumstances of subjects with isolated whiplash injury. Methods This cross
      sectional study involved 75 subjects from traffic accidents with isolated
      whiplash injury classified by Quebec Task Force (QTF). Anthropometric data were
      collected as well as claims about circumstances of traffic accidents. Results
      Distribution of 1st (28; 37.3%), 2nd (25; 33.3%) and 3rd (22; 29.3%) grade of
      whiplash injury was almost equal. Females had smaller anthropometric measurements
      than males; neck circumference was the most significant difference between males
      and females in the context of whiplash injury. The most frequent collision
      mechanism was impact to front (26; 34.7%) or to rear end (26; 34.7%) of a small
      passenger's car. Assertions of participants were that their car damage was
      significant (37; 49.2%) or total (24; 32%). A total of 38 (50.7%) participants
      claimed that they were not wearing safety belt and 52 (69.3%) did not find
      themselves responsible for accident. Conclusion Driving habits of our
      participants facilitate incidence of whiplash injuries, especially in vulnerable
      groups such as women and elderly.

PMID- 29214989
TI  - Long non-coding RNA SPRY4-IT1 promotes development of hepatic cellular carcinoma
      by interacting with ERRalpha and predicts poor prognosis.
AB  - Hepatocellular carcinoma (HCC) has become one of the most common leading causes
      of cancer-related deaths worldwide. This study investigates the role of lncRNA,
      SPRY4-IT1 in the development of HCC. Quantitative real-time PCR (qRT-PCR) was
      performed and the results showed that SPRY4-IT1 expression was up-regulated in
      HCC tissues and high expression of SPRY4-IT1 was associated with poor 5-year
      overall survival in the HCC patient cohort. Clinicopathological analysis showed
      that the expression of SPRY4-IT1 was significantly correlated with TNM stage in
      HCC patients. In vitro CCK-8 assay, colony formation assay, cell invasion and
      migration assays demonstrated that knock-down of SPRY4-IT1 suppressed cell
      proliferation, colony formation, cell invasion and migration in HCC cells. Flow
      cytometric analysis showed that knock-down of SPRY4-IT1 induced cell cycle arrest
      at G0/G1 phase and induced apoptosis. In addition, knock-down of SPRY4-IT1 also
      suppressed the mRNA and protein expression of estrogen-related receptor alpha
      (ERRalpha). Similarly, knock-down of ERRalpha inhibited cell proliferation,
      colony formation, cell invasion and migration in HCC cells. More importantly,
      ERRalpha overexpression antagonized the effects of SPRY4-IT1 knock-down on cell
      proliferation, colony formation, cell invasion and migration in HCC cells. Taken
      together, our data highlights the pivotal role of SPRY4-IT1 in the tumorigenesis
      of HCC.

PMID- 29214990
TI  - RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells
      from bone marrow, adipose tissue, and palatine tonsils.
AB  - Human mesenchymal stem cells (MSCs) are adult multipotent cells that have
      plasticity and inhabit the stroma of diverse tissues. The potential utility of
      MSCs has been heavily investigated in the fields of regenerative medicine and
      cell therapy. However, MSCs represent diverse populations that may depend on the
      tissue of origin. Thus, the ability to identify specific MSC populations has
      remained difficult. Using RNA sequencing, we analyzed the whole transcriptomes of
      bone marrow-derived MSCs (BMs), adipose tissue-derived MSCs (AMs), and tonsil
      derived MSCs (TMs). We categorized highly regulated genes from these MSC groups
      according to functional gene ontology (GO) classification. AMs and TMs showed
      higher expression of genes encoding proteins that function in protein binding,
      growth factor, or cytokine activity in extracellular compartments than BMs.
      Interestingly, TM were highly enriched for genes coding extracellular, protein
      binding proteins compared with AMs. Functional Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis also showed differentially enriched signaling
      pathways between the three MSC groups. Further, we confirmed surface antigens
      expressed in common and in a tissue-specific manner on BMs, AMs, and TMs by flow
      cytometry analysis. This study provides comprehensive characteristics of MSCs
      derived from different tissues to better understand their cellular and molecular
      biology.

PMID- 29214991
TI  - Pseudomonas aeruginosa zinc uptake in chelating environment is primarily mediated
      by the metallophore pseudopaline.
AB  - Metal uptake is vital for all living organisms. In metal scarce conditions a
      common bacterial strategy consists in the biosynthesis of metallophores, their
      export in the extracellular medium and the recovery of a metal-metallophore
      complex through dedicated membrane transporters. Staphylopine is a recently
      described metallophore distantly related to plant nicotianamine that contributes
      to the broad-spectrum metal uptake capabilities of Staphylococcus aureus. Here we
      characterize a four-gene operon (PA4837-PA4834) in Pseudomonas aeruginosa
      involved in the biosynthesis and trafficking of a staphylopine-like metallophore
      named pseudopaline. Pseudopaline differs from staphylopine with regard to the
      stereochemistry of its histidine moiety associated with an alpha ketoglutarate
      moiety instead of pyruvate. In vivo, the pseudopaline operon is regulated by zinc
      through the Zur repressor. The pseudopaline system is involved in nickel uptake
      in poor media, and, most importantly, in zinc uptake in metal scarce conditions
      mimicking a chelating environment, thus reconciling the regulation of the cnt
      operon by zinc with its function as the main zinc importer under these metal
      scarce conditions.

PMID- 29214992
TI  - Charge-Stripe Order and Superconductivity in Ir1-xPtxTe2.
AB  - A combined resistivity and hard x-ray diffraction study of superconductivity and
      charge ordering in Ir Ir1-xPtxTe2, as a function of Pt substitution and
      externally applied hydrostatic pressure, is presented. Experiments are focused on
      samples near the critical composition x c  ~ 0.045 where competition and
      switching between charge order and superconductivity is established. We show that
      charge order as a function of pressure in Ir0.95Pt0.05Te2 is preempted - and
      hence triggered - by a structural transition. Charge ordering appears uniaxially
      along the short crystallographic (1, 0, 1) domain axis with a (1/5, 0, 1/5)
      modulation. Based on these results we draw a charge-order phase diagram and
      discuss the relation between stripe ordering and superconductivity.

PMID- 29214993
TI  - MicroRNA-like RNAs from the same miRNA precursors play a role in cassava chilling
      responses.
AB  - MicroRNAs (miRNAs) are known to play important roles in various cellular
      processes and stress responses. MiRNAs can be identified by analyzing reads from
      high-throughput deep sequencing. The reads realigned to miRNA precursors besides
      canonical miRNAs were initially considered as sequencing noise and ignored from
      further analysis. Here we reported a small-RNA species of phased and half-phased
      miRNA-like RNAs different from canonical miRNAs from cassava miRNA precursors
      detected under four distinct chilling conditions. They can form abundant multiple
      small RNAs arranged along precursors in a tandem and phased or half-phased
      fashion. Some of these miRNA-like RNAs were experimentally confirmed by re
      amplification and re-sequencing, and have a similar qRT-PCR detection ratio as
      their cognate canonical miRNAs. The target genes of those phased and half-phased
      miRNA-like RNAs function in process of cell growth metabolism and play roles in
      protein kinase. Half-phased miR171d.3 was confirmed to have cleavage activities
      on its target gene P-glycoprotein 11, a broad substrate efflux pump across
      cellular membranes, which is thought to provide protection for tropical cassava
      during sharp temperature decease. Our results showed that the RNAs from miRNA
      precursors are miRNA-like small RNAs that are viable negative gene regulators and
      may have potential functions in cassava chilling responses.

PMID- 29214994
TI  - Human liver segments: role of cryptic liver lobes and vascular physiology in the
      development of liver veins and left-right asymmetry.
AB  - Couinaud based his well-known subdivision of the liver into (surgical) segments
      on the branching order of portal veins and the location of hepatic veins.
      However, both segment boundaries and number remain controversial due to an
      incomplete understanding of the role of liver lobes and vascular physiology on
      hepatic venous development. Human embryonic livers (5-10 weeks of development)
      were visualized with Amira 3D-reconstruction and Cinema 4D-remodeling software.
      Starting at 5 weeks, the portal and umbilical veins sprouted portal-vein branches
      that, at 6.5 weeks, had been pruned to 3 main branches in the right hemi-liver,
      whereas all (>10) persisted in the left hemi-liver. The asymmetric branching
      pattern of the umbilical vein resembled that of a "distributing" vessel, whereas
      the more symmetric branching of the portal trunk resembled a "delivering" vessel.
      At 6 weeks, 3-4 main hepatic-vein outlets drained into the inferior caval vein,
      of which that draining the caudate lobe formed the intrahepatic portion of the
      caval vein. More peripherally, 5-6 major tributaries drained both dorsolateral
      regions and the left and right ventromedial regions, implying a "crypto-lobar"
      distribution. Lobar boundaries, even in non-lobated human livers, and functional
      vascular requirements account for the predictable topography and branching
      pattern of the liver veins, respectively.

PMID- 29214995
TI  - Normalizing brain activity across individuals using functional reference mapping.
AB  - Neural activity can be mapped across individuals using brain atlases, but when
      spatial relationships are not equal, these techniques collapse. We map activity
      across individuals using functional registration, based on physiological
      responses to predetermined reference stimuli. Data from several individuals are
      integrated into a common multidimensional stimulus space, where dimensionality
      and axes are defined by these reference stimuli. We used this technique to
      discriminate volatile compounds with a cohort of Drosophila flies, by recording
      odor responses in receptor neurons on the flies' antennae. We propose this
      technique for the development of reliable biological sensors when activity raw
      data cannot be calibrated. In particular, this technique will be useful for
      evaluating physiological measurements in natural chemosensory systems, and
      therefore will allow to exploit the sensitivity and selectivity of olfactory
      receptors present in the animal kingdom for analytical purposes.

PMID- 29214996
TI  - The role of Cdx2 as a lineage specific transcriptional repressor for pluripotent
      network during the first developmental cell lineage segregation.
AB  - The first cellular differentiation event in mouse development leads to the
      formation of the blastocyst consisting of the inner cell mass (ICM) and
      trophectoderm (TE). The transcription factor CDX2 is required for proper TE
      specification, where it promotes expression of TE genes, and represses expression
      of Pou5f1 (OCT4). However its downstream network in the developing embryo is not
      fully characterized. Here, we performed high-throughput single embryo qPCR
      analysis in Cdx2 null embryos to identify CDX2-regulated targets in vivo. To
      identify genes likely to be regulated by CDX2 directly, we performed CDX2 ChIP
      Seq on trophoblast stem (TS) cells. In addition, we examined the dynamics of gene
      expression changes using inducible CDX2 embryonic stem (ES) cells, so that we
      could predict which CDX2-bound genes are activated or repressed by CDX2 binding.
      By integrating these data with observations of chromatin modifications, we
      identify putative novel regulatory elements that repress gene expression in a
      lineage-specific manner. Interestingly, we found CDX2 binding sites within
      regulatory elements of key pluripotent genes such as Pou5f1 and Nanog, pointing
      to the existence of a novel mechanism by which CDX2 maintains repression of OCT4
      in trophoblast. Our study proposes a general mechanism in regulating lineage
      segregation during mammalian development.

PMID- 29214997
TI  - The influences and neural correlates of past and present during gambling in
      humans.
AB  - During financial decision-making tasks, humans often make "rational" decisions,
      where they maximize expected reward. However, this rationality may compete with a
      bias that reflects past outcomes. That is, if one just lost money or won money,
      this may impact future decisions. It is unclear how past outcomes influence
      future decisions in humans, and how neural circuits encode present and past
      information. In this study, six human subjects performed a financial decision
      making task while we recorded local field potentials from multiple brain
      structures. We constructed a model for each subject characterizing bets on each
      trial as a function of present and past information. The models suggest that some
      patients are more influenced by previous trial outcomes (i.e., previous return
      and risk) than others who stick to more fixed decision strategies. In addition,
      past return and present risk modulated with the activity in the cuneus; while
      present return and past risk modulated with the activity in the superior temporal
      gyrus and the angular gyrus, respectively. Our findings suggest that these
      structures play a role in decision-making beyond their classical functions by
      incorporating predictions and risks in humans' decision strategy, and provide new
      insight into how humans link their internal biases to decisions.

PMID- 29214998
TI  - Structural insights into the potency of SK channel positive modulators.
AB  - Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the
      regulation of cellular excitability and have been implicated in neurological and
      cardiovascular diseases through both animal model studies and human genetic
      association studies. Over the past two decades, positive modulators of SK
      channels such as NS309 and 1-EBIO have been developed. Our previous structural
      studies have identified the binding pocket of 1-EBIO and NS309 that is located at
      the interface between the channel and calmodulin. In this study, we took
      advantage of four compounds with potencies varying over three orders of
      magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione
      3-oxime) and SKS-14 (7-fluoro-3-(hydroxyimino)indolin-2-one). A combination of x
      ray crystallographic, computational and electrophysiological approaches was
      utilized to investigate the interactions between the positive modulators and
      their binding pocket. A strong trend exists between the interaction energy of the
      compounds within their binding site calculated from the crystal structures, and
      the potency of these compounds in potentiating the SK2 channel current determined
      by electrophysiological recordings. Our results further reveal that the
      difference in potency of the positive modulators in potentiating SK2 channel
      activity may be attributed primarily to specific electrostatic interactions
      between the modulators and their binding pocket.

PMID- 29214999
TI  - Engineering an aldehyde dehydrogenase toward its substrates, 3-hydroxypropanal
      and NAD+, for enhancing the production of 3-hydroxypropionic acid.
AB  - 3-Hydroxypropionic acid (3-HP) can be produced via the biological route involving
      two enzymatic reactions: dehydration of glycerol to 3-hydroxypropanal (3-HPA) and
      then oxidation to 3-HP. However, commercial production of 3-HP using recombinant
      microorganisms has been hampered with several problems, some of which are
      associated with the toxicity of 3-HPA and the efficiency of NAD+ regeneration. We
      engineered alpha-ketoglutaric semialdehyde dehydrogenase (KGSADH) from
      Azospirillum brasilense for the second reaction to address these issues. The
      residues in the binding sites for the substrates, 3-HPA and NAD+, were
      randomized, and the resulting libraries were screened for higher activity.
      Isolated KGSADH variants had significantly lower Km values for both the
      substrates. The enzymes also showed higher substrate specificities for aldehyde
      and NAD+, less inhibition by NADH, and greater resistance to inactivation by 3
      HPA than the wild-type enzyme. A recombinant Pseudomonas denitrificans strain
      with one of the engineered KGSADH variants exhibited less accumulation of 3-HPA,
      decreased levels of inactivation of the enzymes, and higher cell growth than that
      with the wild-type KGSADH. The flask culture of the P. denitrificans strain with
      the mutant KGSADH resulted in about 40% increase of 3-HP titer (53 mM) compared
      with that using the wild-type enzyme (37 mM).

PMID- 29215000
TI  - The evolution of the macrophage-specific enhancer (Fms intronic regulatory
      element) within the CSF1R locus of vertebrates.
AB  - The Csf1r locus encodes the receptor for macrophage colony-stimulating factor,
      which controls the proliferation, differentiation and survival of macrophages.
      The 300 bp Fms intronic regulatory element (FIRE), within the second intron of
      Csf1r, is necessary and sufficient to direct macrophage-specific transcription.
      We have analysed the conservation and divergence of the FIRE DNA sequence in
      vertebrates. FIRE is present in the same location in the Csf1r locus in reptile,
      avian and mammalian genomes. Nearest neighbor analysis based upon this element
      alone largely recapitulates phylogenies inferred from much larger genomic
      sequence datasets. One core element, containing binding sites for AP1 family and
      the macrophage-specific transcription factor, PU.1, is conserved from lizards to
      humans. Around this element, the FIRE sequence is conserved within clades with
      the most conserved elements containing motifs for known myeloid-expressed
      transcription factors. Conversely, there is little alignment between clades
      outside the AP1/PU.1 element. The analysis favours a hybrid between
      "enhanceosome" and "smorgasbord" models of enhancer function, in which elements
      cooperate to bind components of the available transcription factor milieu.

PMID- 29215001
TI  - Endomucin inhibits VEGF-induced endothelial cell migration, growth, and
      morphogenesis by modulating VEGFR2 signaling.
AB  - Angiogenesis is central to both normal and pathologic processes. Endothelial
      cells (ECs) express O-glycoproteins that are believed to play important roles in
      vascular development and stability. Endomucin-1 (EMCN) is a type I O
      glycosylated, sialic-rich glycoprotein, specifically expressed by venous and
      capillary endothelium. Evidence has pointed to a potential role for EMCN in
      angiogenesis but it had not been directly investigated. In this study, we
      examined the role of EMCN in angiogenesis by modulating EMCN levels both in vivo
      and in vitro. Reduction of EMCN in vivo led to the impairment of angiogenesis
      during normal retinal development in vivo. To determine the cellular basis of
      this inhibition, gain- and loss-of-function studies were performed in human
      retinal EC (HREC) in vitro by EMCN over-expression using adenovirus or EMCN gene
      knockdown by siRNA. We show that EMCN knockdown reduced migration, inhibited cell
      growth without compromising cell survival, and suppressed tube morphogenesis of
      ECs, whereas over-expression of EMCN led to increased migration, proliferation
      and tube formation. Furthermore, knockdown of EMCN suppressed VEGF-induced
      signaling as measured by decreased phospho-VEGFR2, phospho-ERK1/2 and phospho-p38
      MAPK levels. These results suggest a novel role for EMCN as a potent regulator of
      angiogenesis and point to its potential as a new therapeutic target for
      angiogenesis-related diseases.

PMID- 29215002
TI  - On the impact of capillarity for strength at the nanoscale.
AB  - The interior of nanoscale crystals experiences stress that compensates for the
      capillary forces and that can be large, in the order of 1 GPa. Various studies
      have speculated on whether and how this surface-induced stress affects the
      stability and plasticity of small crystals. Yet, experiments have so far failed
      to discriminate between the surface contribution and other, bulk-related size
      effects. To clarify the issue, here we study the variation of the flow stress of
      a nanomaterial while distinctly different variations of the two capillary
      parameters, surface tension, and surface stress, are imposed under control of an
      applied electric potential. Our theory qualifies the suggested impact of surface
      stress as not forceful and instead predicts a significant contribution of the
      surface energy, as measured by the surface tension. The predictions for the
      combined potential-dependence and size-dependence of the flow stress are
      quantitatively supported by the experiment. Previous suggestions, favoring the
      surface stress as the relevant capillary parameter, are not consistent with our
      experiment.

PMID- 29215005
TI  - Disentangling eco-evolutionary dynamics of predator-prey coevolution: the case of
      antiphase cycles.
AB  - The impact of rapid predator-prey coevolution on predator-prey dynamics remains
      poorly understood, as previous modelling studies have given rise to contradictory
      conclusions and predictions. Interpreting and reconciling these contradictions
      has been challenging due to the inherent complexity of model dynamics, defying
      mathematical analysis and mechanistic understanding. We develop a new approach
      here, based on the Geber method for deconstructing eco-evolutionary dynamics, for
      gaining such understanding. We apply this approach to a co-evolutionary predator
      prey model to disentangle the processes leading to either antiphase or 1/4-lag
      cycles. Our analysis reveals how the predator-prey phase relationship is driven
      by the temporal synchronization between prey biomass and defense dynamics. We
      further show when and how prey biomass and trait dynamics become synchronized,
      resulting in antiphase cycles, allowing us to explain and reconcile previous
      modelling and empirical predictions. The successful application of our proposed
      approach provides an important step towards a comprehensive theory on eco
      evolutionary feedbacks in predator-prey systems.

PMID- 29215003
TI  - Rhythmic potassium transport regulates the circadian clock in human red blood
      cells.
AB  - Circadian rhythms organize many aspects of cell biology and physiology to a daily
      temporal program that depends on clock gene expression cycles in most mammalian
      cell types. However, circadian rhythms are also observed in isolated mammalian
      red blood cells (RBCs), which lack nuclei, suggesting the existence of post
      translational cellular clock mechanisms in these cells. Here we show using
      electrophysiological and pharmacological approaches that human RBCs display
      circadian regulation of membrane conductance and cytoplasmic conductivity that
      depends on the cycling of cytoplasmic K+ levels. Using pharmacological
      intervention and ion replacement, we show that inhibition of K+ transport
      abolishes RBC electrophysiological rhythms. Our results suggest that in the
      absence of conventional transcription cycles, RBCs maintain a circadian rhythm in
      membrane electrophysiology through dynamic regulation of K+ transport.

PMID- 29215004
TI  - NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for
      degradation via the ubiquitin ligase RNF19A.
AB  - The adaptor protein TRAF6 has a central function in Toll-like receptor (TLR)
      signalling, yet the molecular mechanisms controlling its activity and stability
      are unclear. Here we show that NLRP11, a primate specific gene, inhibits TLR
      signalling by targeting TRAF6 for degradation. NLRP11 recruits the ubiquitin
      ligase RNF19A to catalyze K48-linked ubiquitination of TRAF6 at multiple sites,
      thereby leading to the degradation of TRAF6. Furthermore, deficiency in either
      NLRP11 or RNF19A abrogates K48-linked ubiquitination and degradation of TRAF6,
      which promotes activation of NF-kappaB and MAPK signalling and increases the
      production of proinflammatory cytokines. Therefore, our findings identify NLRP11
      as a conserved negative regulator of TLR signalling in primate cells and reveal a
      mechanism by which the NLRP11-RNF19A axis targets TRAF6 for degradation.

PMID- 29215006
TI  - Stateful characterization of resistive switching TiO2 with electron beam induced
      currents.
AB  - Metal oxide resistive switches are increasingly important as possible artificial
      synapses in next-generation neuromorphic networks. Nevertheless, there is still
      no codified set of tools for studying properties of the devices. To this end, we
      demonstrate electron beam-induced current measurements as a powerful method to
      monitor the development of local resistive switching in TiO2-based devices. By
      comparing beam energy-dependent electron beam-induced currents with Monte Carlo
      simulations of the energy absorption in different device layers, it is possible
      to deconstruct the origins of filament image formation and relate this to both
      morphological changes and the state of the switch. By clarifying the contrast
      mechanisms in electron beam-induced current microscopy, it is possible to gain
      new insights into the scaling of the resistive switching phenomenon and observe
      the formation of a current leakage region around the switching filament.
      Additionally, analysis of symmetric device structures reveals propagating
      polarization domains.

PMID- 29215007
TI  - Multivalent cross-linking of actin filaments and microtubules through the
      microtubule-associated protein Tau.
AB  - Microtubule-associated proteins regulate microtubule dynamics, bundle actin
      filaments, and cross-link actin filaments with microtubules. In addition,
      aberrant interaction of the microtubule-associated protein Tau with filamentous
      actin is connected to synaptic impairment in Alzheimer's disease. Here we provide
      insight into the nature of interaction between Tau and actin filaments. We show
      that Tau uses several short helical segments to bind in a dynamic, multivalent
      process to the hydrophobic pocket between subdomains 1 and 3 of actin. Although a
      single Tau helix is sufficient to bind to filamentous actin, at least two,
      flexibly linked helices are required for actin bundling. In agreement with a
      structural model of Tau repeat sequences in complex with actin filaments,
      phosphorylation at serine 262 attenuates binding of Tau to filamentous actin.
      Taken together the data demonstrate that bundling of filamentous actin and cross
      linking of the cellular cytoskeleton depend on the metamorphic and multivalent
      nature of microtubule-associated proteins.

PMID- 29215008
TI  - Roles of two types of heparan sulfate clusters in Wnt distribution and signaling
      in Xenopus.
AB  - Wnt proteins direct embryonic patterning, but the regulatory basis of their
      distribution and signal reception remain unclear. Here, we show that endogenous
      Wnt8 protein is distributed in a graded manner in Xenopus embryo and accumulated
      on the cell surface in a punctate manner in association with "N-sulfo-rich
      heparan sulfate (HS)," not with "N-acetyl-rich HS". These two types of HS are
      differentially clustered by attaching to different glypicans as core proteins. N
      sulfo-rich HS is frequently internalized and associated with the signaling
      vesicle, known as the Frizzled/Wnt/LRP6 signalosome, in the presence of Wnt8.
      Conversely, N-acetyl-rich HS is rarely internalized and accumulates Frzb, a
      secreted Wnt antagonist. Upon interaction with Frzb, Wnt8 associates with N
      acetyl-rich HS, suggesting that N-acetyl-rich HS supports Frzb-mediated
      antagonism by sequestering Wnt8 from N-sulfo-rich HS. Thus, these two types of HS
      clusters may constitute a cellular platform for the distribution and signaling of
      Wnt8.

PMID- 29215009
TI  - The end-joining factor Ku acts in the end-resection of double strand break-free
      arrested replication forks.
AB  - Replication requires homologous recombination (HR) to stabilize and restart
      terminally arrested forks. HR-mediated fork processing requires single stranded
      DNA (ssDNA) gaps and not necessarily double strand breaks. We used genetic and
      molecular assays to investigate fork-resection and restart at dysfunctional,
      unbroken forks in Schizosaccharomyces pombe. Here, we report that fork-resection
      is a two-step process regulated by the non-homologous end joining factor Ku. An
      initial resection mediated by MRN-Ctp1 removes Ku from terminally arrested forks,
      generating ~110 bp sized gaps obligatory for subsequent Exo1-mediated long-range
      resection and replication restart. The mere lack of Ku impacts the processing of
      arrested forks, leading to an extensive resection, a reduced recruitment of RPA
      and Rad51 and a slower fork-restart process. We propose that terminally arrested
      forks undergo fork reversal, providing a single DNA end for Ku binding. We
      uncover a role for Ku in regulating end-resection of unbroken forks and in fine
      tuning HR-mediated replication restart.

PMID- 29215010
TI  - Characterization of a membrane-bound C-glucosyltransferase responsible for
      carminic acid biosynthesis in Dactylopius coccus Costa.
AB  - Carminic acid, a glucosylated anthraquinone found in scale insects like
      Dactylopius coccus, has since ancient times been used as a red colorant in
      various applications. Here we show that a membrane-bound C-glucosyltransferase,
      isolated from D. coccus and designated DcUGT2, catalyzes the glucosylation of
      flavokermesic acid and kermesic acid into their respective C-glucosides dcII and
      carminic acid. DcUGT2 is predicted to be a type I integral endoplasmic reticulum
      (ER) membrane protein, containing a cleavable N-terminal signal peptide and a C
      terminal transmembrane helix that anchors the protein to the ER, followed by a
      short cytoplasmic tail. DcUGT2 is found to be heavily glycosylated. Truncated
      DcUGT2 proteins synthesized in yeast indicate the presence of an internal ER
      targeting signal. The cleavable N-terminal signal peptide is shown to be
      essential for the activity of DcUGT2, whereas the transmembrane helix/cytoplasmic
      domains, although important, are not crucial for its catalytic function.

PMID- 29215011
TI  - Tailoring crystallization phases in metallic glass nanorods via nucleus
      starvation.
AB  - Many physical phenomena deviate from their established frameworks when the system
      approaches relevant length scales governing the phenomena. In crystallization,
      the relevant length scales are the nucleation length set by the nucleus size and
      density, and the growth length set by diffusion fields. Here we observe
      unexpected crystallization phenomena at the nanoscale, using metallic glass (MG)
      nanorods and in situ transmission electron microscopy. The asymmetry between
      critical heating and cooling rates disappears for small MG nanorods. Strikingly,
      an apparent single crystalline phase with its composition similar to the glass
      composition is observed for very small rods, in contrast to bulk samples. We
      attribute this to the lack of nuclei in small MG nanorods that approach the
      nucleation length, thus coined the term, nucleus starvation. By controlling the
      MG nanorod diameter and crystallization kinetics, we can tune the number of
      nuclei in a nanorod, thereby tailoring the resulting crystallization phases.

PMID- 29215012
TI  - REST regulates the cell cycle for cardiac development and regeneration.
AB  - Despite the importance of cardiomyocyte proliferation in cardiac development and
      regeneration, the mechanisms that promote cardiomyocyte cell cycle remain
      incompletely understood. RE1 silencing transcription factor (REST) is a
      transcriptional repressor of neuronal genes. Here we show that REST also
      regulates the cardiomyocyte cell cycle. REST binds and represses the cell cycle
      inhibitor gene p21 and is required for mouse cardiac development and
      regeneration. Rest deletion de-represses p21 and inhibits the cardiomyocyte cell
      cycle and proliferation in embryonic or regenerating hearts. By contrast, REST
      overexpression in cultured cardiomyocytes represses p21 and increases
      proliferation. We further show that p21 knockout rescues cardiomyocyte cell cycle
      and proliferation defects resulting from Rest deletion. Our study reveals a REST
      p21 regulatory axis as a mechanism for cell cycle progression in cardiomyocytes,
      which might be exploited therapeutically to enhance cardiac regeneration.

PMID- 29215013
TI  - Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and
      sugar levels in Mycobacterium tuberculosis.
AB  - Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic
      flux and is critical for ATP production in all organisms, with tight regulation
      by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in
      bacterial pathogens are poorly understood. Here we report biochemical, structural
      and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and
      glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a
      molecular "OR logic gate" to tightly regulate energy and glucose metabolism. G6P
      was found to bind to a previously unknown site adjacent to the canonical site for
      AMP. Kinetic data and structural network analysis further show that AMP and G6P
      work synergistically as allosteric activators. Importantly, metabolome profiling
      in the Mtb surrogate, Mycobacterium bovis BCG, reveals significant changes in AMP
      and G6P levels during nutrient deprivation, which provides insights into how a
      PYK OR gate would function during the stress of Mtb infection.

PMID- 29215014
TI  - Controlled spin switching in a metallocene molecular junction.
AB  - The active control of a molecular spin represents one of the main challenges in
      molecular spintronics. Up to now spin manipulation has been achieved through the
      modification of the molecular structure either by chemical doping or by external
      stimuli. However, the spin of a molecule adsorbed on a surface depends primarily
      on the interaction between its localized orbitals and the electronic states of
      the substrate. Here we change the effective spin of a single molecule by
      modifying the molecule/metal interface in a controlled way using a low
      temperature scanning tunneling microscope. A nickelocene molecule reversibly
      switches from a spin 1 to 1/2 when varying the electrode-electrode distance from
      tunnel to contact regime. This switching is experimentally evidenced by inelastic
      and elastic spin-flip mechanisms observed in reproducible conductance
      measurements and understood using first principle calculations. Our work
      demonstrates the active control over the spin state of single molecule devices
      through interface manipulation.

PMID- 29215015
TI  - Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors.
AB  - STING is an innate immune cytosolic adaptor for DNA sensors that engage malaria
      parasite (Plasmodium falciparum) or other pathogen DNA. As P. falciparum infects
      red blood cells and not leukocytes, how parasite DNA reaches such host cytosolic
      DNA sensors in immune cells is unclear. Here we show that malaria parasites
      inside red blood cells can engage host cytosolic innate immune cell receptors
      from a distance by secreting extracellular vesicles (EV) containing parasitic
      small RNA and genomic DNA. Upon internalization of DNA-harboring EVs by human
      monocytes, P. falciparum DNA is released within the host cell cytosol, leading to
      STING-dependent DNA sensing. STING subsequently activates the kinase TBK1, which
      phosphorylates the transcription factor IRF3, causing IRF3 to translocate to the
      nucleus and induce STING-dependent gene expression. This DNA-sensing pathway may
      be an important decoy mechanism to promote P. falciparum virulence and thereby
      may affect future strategies to treat malaria.

PMID- 29215016
TI  - low neurotrophin receptor CD271 regulates phenotype switching in melanoma.
AB  - Cutaneous melanoma represents the most fatal skin cancer due to its high
      metastatic capacity. According to the "phenotype switching" model, the aggressive
      nature of melanoma cells results from their intrinsic potential to dynamically
      switch from a high-proliferative/low-invasive to a low-proliferative/high
      invasive state. Here we identify the low affinity neurotrophin receptor CD271 as
      a key effector of phenotype switching in melanoma. CD271 plays a dual role in
      this process by decreasing proliferation, while simultaneously promoting
      invasiveness. Dynamic modification of CD271 expression allows tumor cells to grow
      at low levels of CD271, to reduce growth and invade when CD271 expression is
      high, and to re-expand at a distant site upon decrease of CD271 expression.
      Mechanistically, the cleaved intracellular domain of CD271 controls
      proliferation, while the interaction of CD271 with the neurotrophin receptor Trk
      A modulates cell adhesiveness through dynamic regulation of a set of cholesterol
      synthesis genes relevant for patient survival.

PMID- 29215017
TI  - Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys
      peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7210.
AB  - Peroxiredoxins (Prxs) are vital regulators of intracellular reactive oxygen
      species levels in all living organisms. Their activity depends on one or two
      catalytically active cysteine residues, the peroxidatic Cys (CP) and, if present,
      the resolving Cys (CR). A detailed catalytic cycle has been derived for typical 2
      Cys Prxs, however, little is known about the catalytic cycle of 1-Cys Prxs. We
      have characterized Prx6 from the cyanobacterium Anabaena sp. strain PCC7120
      (AnPrx6) and found that in addition to the expected peroxidase activity, AnPrx6
      can act as a molecular chaperone in its dimeric state, contrary to other Prxs.
      The AnPrx6 crystal structure at 2.3 A resolution reveals different active site
      conformations in each monomer of the asymmetric obligate homo-dimer. Molecular
      dynamic simulations support the observed structural plasticity. A FSH motif,
      conserved in 1-Cys Prxs, precedes the active site PxxxTxxCp signature and might
      contribute to the 1-Cys Prx reaction cycle.

PMID- 29215018
TI  - Evidence for a topological excitonic insulator in InAs/GaSb bilayers.
AB  - Electron-hole pairing can occur in a dilute semimetal, transforming the system
      into an excitonic insulator state in which a gap spontaneously appears at the
      Fermi surface, analogous to a Bardeen-Cooper-Schrieffer (BCS) superconductor.
      Here, we report optical spectroscopic and electronic transport evidence for the
      formation of an excitonic insulator gap in an inverted InAs/GaSb quantum-well
      system at low temperatures and low electron-hole densities. Terahertz
      transmission spectra exhibit two absorption lines that are quantitatively
      consistent with predictions from the pair-breaking excitation dispersion
      calculated based on the BCS gap equation. Low-temperature electronic transport
      measurements reveal a gap of ~2 meV (or ~25 K) with a critical temperature of ~10
      K in the bulk, together with quantized edge conductance, suggesting the
      occurrence of a topological excitonic insulator phase.

PMID- 29215020
TI  - Simultaneously improving the mechanical and electrical properties of poly(vinyl
      alcohol) composites by high-quality graphitic nanoribbons.
AB  - Although carbon nanotubes (CNTs) have shown great potential for enhancing the
      performance of polymer matrices, their reinforcement role still needs to be
      further improved. Here we implement a structural modification of multi-walled
      CNTs (MWCNTs) to fully utilize their fascinating mechanical and electrical
      properties via longitudinal splitting of MWCNTs into graphitic nanoribbons
      (GNRs). This nanofiller design strategy is advantageous for surface
      functionalization, strong interface adhesion as well as boosting the interfacial
      contact area without losing the intrinsic graphitic structure. The obtained GNRs
      have planar geometry, quasi-1D structure and high-quality crystallinity, which
      outperforms their tubular counterparts, delivering a superior load-bearing
      efficiency and conductive network for realizing a synchronous improvement of the
      mechanical and electrical properties of a PVA-based composite. Compared to
      PVA/CNTs, the tensile strength, Young's modulus and electrical conductivity of
      the PVA/GNR composite at a filling concentration of 3.6 vol.% approach 119.1 MPa,
      5.3 GPa and 2.4 * 10-4 S m-1, with increases of 17%, 32.5% and 5.9 folds,
      respectively. The correlated mechanics is further rationalized by finite element
      analysis, the generalized shear-lag theory and the fracture mechanisms.

PMID- 29215019
TI  - ciaR impacts biofilm formation by regulating an arginine biosynthesis pathway in
      Streptococcus sanguinis SK36.
AB  - Streptococcus sanguinis is an early colonizer of the tooth surface and competes
      with oral pathogens such as Streptococcus mutans to maintain oral health.
      However, little is known about its mechanism of biofilm formation. Here, we show
      that mutation of the ciaR gene, encoding the response regulator of the CiaRH two
      component system in S. sanguinis SK36, produced a fragile biofilm. Cell
      aggregation, gtfP gene expression and water-insoluble glucan production were all
      reduced, which suggested polysaccharide production was decreased in DeltaciaR.
      RNA sequencing and qRT-PCR revealed that arginine biosynthesis genes (argR, argB,
      argC, argG, argH and argJ) and two arginine/histidine permease genes (SSA_1568
      and SSA_1569) were upregulated in DeltaciaR. In contrast to DeltaciaR, most of
      strains constructed to contain deletions in each of these genes produced more
      biofilm and water-insoluble glucan than SK36. A DeltaciaRDeltaargB double mutant
      was completely restored for the gtfP gene expression, glucan production and
      biofilm formation ability that was lost in DeltaciaR, indicating that argB was
      essential for ciaR to regulate biofilm formation. We conclude that by promoting
      the expression of arginine biosynthetic genes, especially argB gene, the ciaR
      mutation reduced polysaccharide production, resulting in the formation of a
      fragile biofilm in Streptococcus sanguinis.

PMID- 29215021
TI  - An improved ENSO simulation by representing chlorophyll-induced climate feedback
      in the NCAR Community Earth System Model.
AB  - The El Nino-Southern oscillation (ENSO) simulated in the Community Earth System
      Model of the National Center for Atmospheric Research (NCAR CESM) is much
      stronger than in reality. Here, satellite data are used to derive a statistical
      relationship between interannual variations in oceanic chlorophyll (CHL) and sea
      surface temperature (SST), which is then incorporated into the CESM to represent
      oceanic chlorophyll -induced climate feedback in the tropical Pacific. Numerical
      runs with and without the feedback (referred to as feedback and non-feedback
      runs) are performed and compared with each other. The ENSO amplitude simulated in
      the feedback run is more accurate than that in the non-feedback run;
      quantitatively, the Nino3 SST index is reduced by 35% when the feedback is
      included. The underlying processes are analyzed and the results show that
      interannual CHL anomalies exert a systematic modulating effect on the solar
      radiation penetrating into the subsurface layers, which induces differential
      heating in the upper ocean that affects vertical mixing and thus SST. The
      statistical modeling approach proposed in this work offers an effective and
      economical way for improving climate simulations.

PMID- 29215022
TI  - Mineral analysis of complete dog and cat foods in the UK and compliance with
      European guidelines.
AB  - Mineral content of complete pet food is regulated to ensure health of the
      companion animal population. Analysis of adherence to these regulatory guidelines
      has not been conducted. Here, mineral composition of complete wet (n = 97) and
      dry (n = 80) canine and feline pet food sold in the UK was measured to assess
      compliance with EU guidelines. A majority of foods complied with >=8 of 11
      guidelines (99% and 83% for dry and wet food, respectively), but many failed to
      provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional
      maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry
      food were fully compliant. Some foods (20-30% of all analysed) had mineral
      imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1).
      Foods with high fish content had high levels of undesirable metal elements such
      as arsenic. This study highlights broad non-compliance of a range of popular pet
      foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods,
      respectively). If fed exclusively and over an extended period, a number of these
      pet foods could impact the general health of companion animals.

PMID- 29215023
TI  - A Pilot Characterization of the Human Chronobiome.
AB  - Physiological function, disease expression and drug effects vary by time-of-day.
      Clock disruption in mice results in cardio-metabolic, immunological and
      neurological dysfunction; circadian misalignment using forced desynchrony
      increases cardiovascular risk factors in humans. Here we integrated data from
      remote sensors, physiological and multi-omics analyses to assess the feasibility
      of detecting time dependent signals - the chronobiome - despite the "noise"
      attributable to the behavioral differences of free-living human volunteers. The
      majority (62%) of sensor readouts showed time-specific variability including the
      expected variation in blood pressure, heart rate, and cortisol. While variance in
      the multi-omics is dominated by inter-individual differences, temporal patterns
      are evident in the metabolome (5.4% in plasma, 5.6% in saliva) and in several
      genera of the oral microbiome. This demonstrates, despite a small sample size and
      limited sampling, the feasibility of characterizing at scale the human
      chronobiome "in the wild". Such reference data at scale are a prerequisite to
      detect and mechanistically interpret discordant data derived from patients with
      temporal patterns of disease expression, to develop time-specific therapeutic
      strategies and to refine existing treatments.

PMID- 29215025
TI  - Co-expression of mFat-1 and pig IGF-1 genes by recombinant plasmids in modified
      chitosan nanoparticles and its synergistic effect on mouse immunity.
AB  - To develop a cost-effective molecular regulator to improve growth metabolism and
      immunity of animals, a recombinant plasmid co-expressing fatty acid desaturase
      (mFat-1) and pig insulin growth like factor 1 (IGF-1) genes was constructed by
      the 2 A self-cleavage technique. After entrapment within modified chitosan
      nanoparticles (chitosan modified with polyethyleneglycol-polyethylenimine, CPP),
      the recombinant plasmid was injected intramuscularly into mice. Compared with
      controls, co-expression of mFat-1 and IGF-1 significantly raised the level of
      serum IGF-1, and increased the liver and muscle docosa hexaenoic acid (DHA)
      content. Th and Tc cell levels were also elevated, as were expression levels of
      serum IL-4 and IL-6 genes. These results demonstrate that the immunity and
      metabolism of an animal can be effectively improved by co-expression of mFat-1
      and IGF-1 genes in vivo, which may contribute to further development of novel
      immunomodulators with beneficial effects on growth metabolism and immunity.

PMID- 29215024
TI  - Identification of sRNA mediated responses to nutrient depletion in Burkholderia
      pseudomallei.
AB  - The Burkholderia genus includes many species that are known to survive in diverse
      environmental conditions including low nutrient environments. One species,
      Burkholderia pseudomallei is a versatile pathogen that can survive in a wide
      range of hosts and environmental conditions. In this study, we investigated how a
      nutrient depleted growth environment evokes sRNA mediated responses by B.
      pseudomallei. Computationally predicted B. pseudomallei D286 sRNAs were mapped to
      RNA-sequencing data for cultures grown under two conditions: (1) BHIB as a
      nutrient rich media reference environment and (2) M9 media as a nutrient depleted
      stress environment. The sRNAs were further selected to identify potentially cis
      encoded systems by investigating their possible interactions with their flanking
      genes. The mappings of predicted sRNA genes and interactions analysis to their
      flanking genes identified 12 sRNA candidates that may possibly have cis-acting
      regulatory roles that are associated to a nutrient depleted growth environment.
      Our approach can be used for identifying novel sRNA genes and their possible role
      as cis-mediated regulatory systems.

PMID- 29215026
TI  - Additive manufacture of complex 3D Au-containing nanocomposites by simultaneous
      two-photon polymerisation and photoreduction.
AB  - The fabrication of complex three-dimensional gold-containing nanocomposite
      structures by simultaneous two-photon polymerisation and photoreduction is
      demonstrated. Increased salt delivers reduced feature sizes down to line widths
      as small as 78 nm, a level of structural intricacy that represents a significant
      advance in fabrication complexity. The development of a general methodology to
      efficiently mix pentaerythritol triacrylate (PETA) with gold chloride hydrate
      (HAuCl4?3H2O) is reported, where the gold salt concentration is adjustable on
      demand from zero to 20 wt%. For the first-time 7-Diethylamino-3-thenoylcoumarin
      (DETC) is used as the photoinitiator. Only 0.5 wt% of DETC was required to
      promote both polymerisation and photoreduction of up to 20 wt% of gold salt. This
      efficiency is the highest reported for Au-containing composite fabrication by two
      photon lithography. Transmission Electron Microscopy (TEM) analysis confirmed the
      presence of small metallic nanoparticles (5.4 +/- 1.4 nm for long axis / 3.7 +/-
      0.9 nm for short axis) embedded within the polymer matrix, whilst X-ray
      Photoelectron Spectroscopy (XPS) confirmed that they exist in the zero valent
      oxidation state. UV-vis spectroscopy defined that they exhibit the property of
      localised surface plasmon resonance (LSPR). The capability demonstrated in this
      study opens up new avenues for a range of applications, including plasmonics,
      metamaterials, flexible electronics and biosensors.

PMID- 29215027
TI  - Altered human voice processing in the frontal cortex and a developmental language
      delay in 3- to 5-year-old children with autism spectrum disorder.
AB  - The inferior frontal and superior temporal areas in the left hemisphere are
      crucial for human language processing. In the present study, we investigated the
      magnetic mismatch field (MMF) evoked by voice stimuli in 3- to 5-year-old
      typically developing (TD) children and children with autism spectrum disorder
      (ASD) using child-customized magnetoencephalography (MEG). The children with ASD
      exhibited significantly decreased activation in the left superior temporal gyrus
      compared with the TD children for the MMF amplitude. If we classified the
      children with ASD according to the presence of a speech onset delay (ASD - SOD
      and ASD - NoSOD, respectively) and compared them with the TD children, both ASD
      groups exhibited decreased activation in the left superior temporal gyrus
      compared with the TD children. In contrast, the ASD - SOD group exhibited
      increased activity in the left frontal cortex (i.e., pars orbitalis) compared
      with the other groups. For all children with ASD, there was a significant
      negative correlation between the MMF amplitude in the left pars orbitalis and
      language performance. This investigation is the first to show a significant
      difference in two distinct MMF regions in ASD - SOD children compared with TD
      children.

PMID- 29215028
TI  - Effect of canola oil consumption on memory, synapse and neuropathology in the
      triple transgenic mouse model of Alzheimer's disease.
AB  - In recent years consumption of canola oil has increased due to lower cost
      compared with olive oil and the perception that it shares its health benefits.
      However, no data are available on the effect of canola oil intake on Alzheimer's
      disease (AD) pathogenesis. Herein, we investigated the effect of chronic daily
      consumption of canola oil on the phenotype of a mouse model of AD that develops
      both plaques and tangles (3xTg). To this end mice received either regular chow or
      a chow diet supplemented with canola oil for 6 months. At this time point we
      found that chronic exposure to the canola-rich diet resulted in a significant
      increase in body weight and impairments in their working memory together with
      decrease levels of post-synaptic density protein-95, a marker of synaptic
      integrity, and an increase in the ratio of insoluble Abeta 42/40. No significant
      changes were observed in tau phosphorylation and neuroinflammation. Taken
      together, our findings do not support a beneficial effect of chronic canola oil
      consumption on two important aspects of AD pathophysiology which includes memory
      impairments as well as synaptic integrity. While more studies are needed, our
      data do not justify the current trend aimed at replacing olive oil with canola
      oil.

PMID- 29215029
TI  - mTORC1 Signaling is a Critical Regulator of Postnatal Tendon Development.
AB  - Tendons transmit contractile forces between musculoskeletal tissues. Whereas the
      biomechanical properties of tendons have been studied extensively, the molecular
      mechanisms regulating postnatal tendon development are not well understood. Here
      we examine the role of mTORC1 signaling in postnatal tendon development using
      mouse genetic approaches. Loss of mTORC1 signaling by removal of Raptor in
      tendons caused severe tendon defects postnatally, including decreased tendon
      thickness, indicating that mTORC1 is necessary for postnatal tendon development.
      By contrast, activation of mTORC1 signaling in tendons increased tendon cell
      numbers and proliferation. In addition, Tsc1 conditional knockout mice presented
      severely disorganized collagen fibers and neovascularization in the tendon
      midsubstance. Interestingly, collagen fibril diameter was significantly reduced
      in both Raptor and Tsc1 conditional knockout mice, albeit with variations in
      severity. We performed RNA-seq analysis using Achilles tendons to investigate the
      molecular changes underlying these tendon phenotypes. Raptor conditional knockout
      mice showed decreased extracellular matrix (ECM) structure-related gene
      expression, whereas Tsc1 conditional knockout mice exhibited changes in genes
      regulating TGF-beta/BMP/FGF signaling, as well as in genes controlling ECM
      structure and disassembly. Collectively, our studies suggest that maintaining
      physiological levels of mTORC1 signaling is essential for postnatal tendon
      development and maturation.

PMID- 29215031
TI  - A Mechanistic Model of Human Recall of Social Network Structure and Relationship
      Affect.
AB  - The social brain hypothesis argues that the need to deal with social challenges
      was key to our evolution of high intelligence. Research with non-human primates
      as well as experimental and fMRI studies in humans produce results consistent
      with this claim, leading to an estimate that human primary groups should consist
      of roughly 150 individuals. Gaps between this prediction and empirical
      observations can be partially accounted for using "compression heuristics", or
      schemata that simplify the encoding and recall of social information. However,
      little is known about the specific algorithmic processes used by humans to store
      and recall social information. We describe a mechanistic model of human network
      recall and demonstrate its sufficiency for capturing human recall behavior
      observed in experimental contexts. We find that human recall is predicated on
      accurate recall of a small number of high degree network nodes and the
      application of heuristics for both structural and affective information. This
      provides new insight into human memory, social network evolution, and
      demonstrates a novel approach to uncovering human cognitive operations.

PMID- 29215030
TI  - TRAF3 negatively regulates platelet activation and thrombosis.
AB  - CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily,
      binds to CD40, leading to many effects depending on target cell type. Platelets
      express CD40L and are a major source of soluble CD40L. CD40L has been shown to
      potentiate platelet activation and thrombus formation, involving both CD40
      dependent and -independent mechanisms. A family of proteins called TNF receptor
      associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling.
      Platelets express several TRAFs. It has been shown that TRAF2 plays a role in
      CD40L-mediated platelet activation. Here we show that platelet also express
      TRAF3, which plays a negative role in regulating platelet activation. Thrombin-
      or collagen-induced platelet aggregation and secretion are increased in TRAF3
      knockout mice. The expression levels of collagen receptor GPVI and integrin
      alphaIIbbeta3 in platelets were not affected by deletion of TRAF3, suggesting
      that increased platelet activation in the TRAF3 knockout mice was not due to
      increased expression platelet receptors. Time to formation of thrombi in a FeCl3
      induced thrombosis model was significantly shortened in the TRAF3 knockout mice.
      However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus,
      TRAF3 plays a negative role in platelet activation and in thrombus formation in
      vivo.

PMID- 29215032
TI  - Electrically Tunable Fano Resonance from the Coupling between Interband
      Transition in Monolayer Graphene and Magnetic Dipole in Metamaterials.
AB  - Fano resonance modulated effectively by external perturbations can find more
      flexible and important applications in practice. We theoretically study
      electrically tunable Fano resonance with asymmetric line shape over an extremely
      narrow frequency range in the reflection spectra of metamaterials. The
      metamaterials are composed of a metal nanodisk array on graphene, a dielectric
      spacer, and a metal substrate. The near-field plasmon hybridization between
      individual metal nanodisks and the metal substrate results into the excitation of
      a broad magnetic dipole. There exists a narrow interband transition dependent of
      Fermi energy E f , which manifests itself as a sharp spectral feature in the
      effective permittivity epsilon g of graphene. The coupling of the narrow
      interband transition to the broad magnetic dipole leads to the appearance of Fano
      resonance, which can be electrically tuned by applying a bias voltage to graphene
      to change E f . The Fano resonance will shift obviously and its asymmetric line
      shape will become more pronounced, when E f is changed for the narrow interband
      transition to progressively approach the broad magnetic dipole.

PMID- 29215033
TI  - Transplantation of a quaternary structure neutralizing antibody epitope from
      dengue virus serotype 3 into serotype 4.
AB  - Dengue vaccine trials have revealed deficits in our understanding of the
      mechanisms of protective immunity, demonstrating a need to measure epitope
      specific antibody responses against each DENV serotype. HmAb 5J7 binds to a
      complex, 3-monomer spanning quaternary epitope in the DENV3 envelope (E) protein,
      but it is unclear whether all interactions are needed for neutralization.
      Structure guided design and reverse genetics were used to sequentially transplant
      larger portions of the DENV3-specific 5J7 mAb epitope into dengue virus serotype
      4 (DENV4). We observed complete binding and neutralization only when the entire 3
      monomer spanning epitope was transplanted into DENV4, providing empirical proof
      that cooperative monomer-hmAb 5J7 interactions maximize activity. The rDENV4/3
      virus containing the most expanded 5J7 epitope was also significantly more
      sensitive than WT DENV4 to neutralization by DENV3 primary immune sera. We
      conclude that the hinge-spanning region of the 5J7 quaternary epitope is a target
      for serotype-specific neutralizing antibodies after DENV3 infection.

PMID- 29215034
TI  - Local field potentials are induced by visually evoked spiking activity in macaque
      cortical area MT.
AB  - Local field potentials (LFP) have been the focus of many recent studies in
      systems neuroscience. However, the exact neural basis of these signals remains
      unclear. To address this question, we determined the relationship between LFP
      signals and another, much better understood, signature of neural activity: action
      potentials. Specifically, we focused on the relationship between the amplitude of
      stimulus-induced LFPs and the magnitude of spiking activity in visual cortex of
      non-human primates. Our trial-by-trial correlation analyses between these two
      components of extracellular signals in macaque visual cortex show that the spike
      rate is coupled to the LFP amplitude with a surprisingly long latency, typically
      50 ms. Our analysis shows that the neural spike rate is a significant predictor
      of the LFP amplitude. This limits the functional interpretation of LFP signals
      beyond that based on spiking activities.

PMID- 29215035
TI  - Influence of genetic ancestry and socioeconomic status on type 2 diabetes in the
      diverse Colombian populations of Choco and Antioquia.
AB  - Differences in genetic ancestry and socioeconomic status (SES) among Latin
      American populations have been linked to health disparities for a number of
      complex diseases, such as diabetes. We used a population genomic approach to
      investigate the role that genetic ancestry and socioeconomic status (SES) play in
      the epidemiology of type 2 diabetes (T2D) for two Colombian populations: Choco
      (Afro-Latino) and Antioquia (Mestizo). Choco has significantly higher predicted
      genetic risk for T2D compared to Antioquia, and the elevated predicted risk for
      T2D in Choco is correlated with higher African ancestry. Despite its elevated
      predicted genetic risk, the population of Choco has a three-times lower observed
      T2D prevalence than Antioquia, indicating that environmental factors better
      explain differences in T2D outcomes for Colombia. Choco has substantially lower
      SES than Antioquia, suggesting that low SES in Choco serves as a protective
      factor against T2D. The combination of lower prevalence of T2D and lower SES in
      Choco may seem surprising given the protective nature of elevated SES in many
      populations in developed countries. However, low SES has also been documented to
      be a protective factor in rural populations in less developed countries, and this
      appears to be the case when comparing Choco to Antioquia.

PMID- 29215036
TI  - Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with
      pharmacological properties and pathophysiology of envenomation.
AB  - The proteome composition of Echis carinatus carinatus venom (ECV) from India was
      studied for the first time by tandem mass spectrometry analysis. A total of 90,
      47, and 22 distinct enzymatic and non-enzymatic proteins belonging to 15, 10, and
      6 snake venom protein families were identified in ECV by searching the ESI-LC
      MS/MS data against non-redundant protein databases of Viperidae (taxid 8689),
      Echis (taxid 8699) and Echis carinatus (taxid 40353), respectively. However,
      analysis of MS/MS data against the Transcriptome Shotgun Assembly sequences (87
      entries) of conger E. coloratus identified only 14 proteins in ECV. Snake venom
      metalloproteases and snaclecs, the most abundant enzymatic and non-enzymatic
      proteins, respectively in ECV account for defibrinogenation and the strong in
      vitro pro-coagulant activity. Further, glutaminyl cyclase, aspartic protease,
      aminopeptidase, phospholipase B, vascular endothelial growth factor, and nerve
      growth factor were reported for the first time in ECV. The proteome composition
      of ECV was well correlated with its biochemical and pharmacological properties
      and clinical manifestations observed in Echis envenomed patients. Neutralization
      of enzymes and pharmacological properties of ECV, and immuno-cross-reactivity
      studies unequivocally point to the poor recognition of <20 kDa ECV proteins, such
      as PLA2, subunits of snaclec, and disintegrin by commercial polyvalent antivenom.

PMID- 29215038
TI  - Differential Raman backscattering cross sections of black carbon nanoparticles.
AB  - We report the measurements of the differential Raman backscattering cross
      sections for several carbonaceous ultrafine particles of environmental
      relevances. These were obtained by dispersing the target particles in liquid
      water which was used as the internal standard reference. The optical collection
      was performed in a configuration to ensure a detection as close as possible to
      the backward direction. These are the first cross sections on black carbon-type
      particles although Raman spectroscopy is widely used in Carbon science. The high
      values of the cross sections, few 10-28 cm2.sr-1.atom-1, reflect resonance
      effects that take advantages of the disordered polyaromatic structures. Because
      they were measured in conditions intended to mimic the aerosol phase, these
      measurements provide a crucial step to move toward quantitative Raman
      spectroscopy and enable development of dedicated teledetection of black carbon in
      the atmosphere and in combustion chambers.

PMID- 29215037
TI  - Pre-treatment inflammatory indexes as predictors of survival and cetuximab
      efficacy in metastatic colorectal cancer patients with wild-type RAS.
AB  - This study aims at evaluating the prognostic significance of neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to
      monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in
      metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five
      patients receiving cetuximab for mCRC were categorized into the high or low NLR,
      PLR, LMR, and SII groups based on their median index values. Univariate and
      multivariate survival analysis were performed to identify the indexes'
      correlation with progression-free survival (PFS) and overall survival (OS). In
      the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte
      counts, monocyte counts, NLR, PLR, and LDH were associated with survival.
      Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR]
      3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil
      counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte
      counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR
      3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS
      and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were
      potential biomarkers to predict the survival of mCRC patients with cetuximab
      therapy.

PMID- 29215039
TI  - Semantic discrimination impacts tDCS modulation of verb processing.
AB  - Motor cortex activation observed during body-related verb processing hints at
      simulation accompanying linguistic understanding. By exploiting the up- and down
      regulation that anodal and cathodal transcranial direct current stimulation
      (tDCS) exert on motor cortical excitability, we aimed at further characterizing
      the functional contribution of the motor system to linguistic processing. In a
      double-blind sham-controlled within-subjects design, online stimulation was
      applied to the left hemispheric hand-related motor cortex of 20 healthy subjects.
      A dual, double-dissociation task required participants to semantically
      discriminate concrete (hand/foot) from abstract verb primes as well as to respond
      with the hand or with the foot to verb-unrelated geometric targets. Analyses were
      conducted with linear mixed models. Semantic priming was confirmed by faster and
      more accurate reactions when the response effector was congruent with the verb's
      body part. Cathodal stimulation induced faster responses for hand verb primes
      thus indicating a somatotopical distribution of cortical activation as induced by
      body-related verbs. Importantly, this effect depended on performance in semantic
      discrimination. The current results point to verb processing being selectively
      modifiable by neuromodulation and at the same time to a dependence of tDCS
      effects on enhanced simulation. We discuss putative mechanisms operating in this
      reciprocal dependence of neuromodulation and motor resonance.

PMID- 29215040
TI  - Sex-related pharmacokinetic differences and mechanisms of metapristone (RU486
      metabolite).
AB  - Metapristone is the primary metabolite of the abortifacient mifepristone (RU486),
      and is being developed as a safe and effective cancer metastatic chemopreventive
      agent for both sexes. Here, we systematically investigated the sex-related
      pharmacokinetics of metapristone in both rats and dogs, and explored the related
      mechanisms of actions. Administration of metapristone to rats and dogs showed
      that plasma concentrations of metapristone (AUC, C max ) were significantly
      higher in female dogs and rats than in males. The sex-related differences in
      pharmacokinetics become more significant after ten consecutive days of oral
      administration. Female liver microsomes metabolized metapristone significantly
      slower than the male ones. The results from P450 reaction phenotyping using
      recombinant cDNA-expressed human CYPs in conjunction with specific CYP inhibitors
      suggested that CYP1A2 and CYP3A4 are the predominant CYPs involved in the
      metapristone metabolism, which were further confirmed by the enhanced protein
      levels of CYP1A2 and CYP3A4 induced by 1-week oral administration of metapristone
      to rats. The highest tissue concentration of metapristone was found in the liver.
      The study demonstrates, for the first time, the sex-related pharmacokinetics of
      metapristone, and reveals that activities of liver microsomal CYP1A2 and CYP3A4
      as well as the renal clearance are primarily responsible for the sex-related
      pharmacokinetics.

PMID- 29215041
TI  - CRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes.
AB  - The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9
      system revolutionized the field of gene editing but viral delivery of the
      CRISPR/Cas9 system has not been fully explored. Here we adapted clinically
      relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for
      the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present
      a platform enabling fast transfer of the Cas9 gene and gRNA expression units into
      the HCAdV genome including the option to choose between constitutive or inducible
      Cas9 expression and gRNA multiplexing. Efficacy and versatility of this pipeline
      was exemplified by producing different CRISPR/Cas9-HCAdV targeting the human
      papillomavirus (HPV) 18 oncogene E6, the dystrophin gene causing Duchenne
      muscular dystrophy (DMD) and the HIV co-receptor C-C chemokine receptor type 5
      (CCR5). All CRISPR/Cas9-HCAdV proved to be efficient to deliver the respective
      CRISPR/Cas9 expression units and to introduce the desired DNA double strand
      breaks at their intended target sites in immortalized and primary cells.

PMID- 29215043
TI  - beta-Sheet Structure within the Extracellular Domain of C99 Regulates
      Amyloidogenic Processing.
AB  - Familial mutations in C99 can increase the total level of the soluble Abeta
      peptides produced by proteolysis, as well as the Abeta42/Abeta40 ratio, both of
      which are linked to the progression of Alzheimer's disease. We show that the
      extracellular sequence of C99 forms beta-sheet structure upon interaction with
      membrane bilayers. Mutations that disrupt this structure result in a significant
      increase in Abeta production and, in specific cases, result in an increase in the
      amount of Abeta42 relative to Abeta40. Fourier transform infrared and solid-state
      NMR spectroscopic studies reveal a central beta-hairpin within the extracellular
      sequence comprising Y10-E11-V12 and L17-V18-F19 connected by a loop involving H13
      H14-Q15. These results suggest how familial mutations in the extracellular
      sequence influence C99 processing and provide a structural basis for the
      development of small molecule modulators that would reduce Abeta production.

PMID- 29215044
TI  - Photonic time crystals.
AB  - When space (time) translation symmetry is spontaneously broken, the space crystal
      (time crystal) forms; when permittivity and permeability periodically vary with
      space (time), the photonic crystal (photonic time crystal) forms. We proposed the
      concept of photonic time crystal and rewritten the Maxwell's equations. Utilizing
      Finite Difference Time Domain (FDTD) method, we simulated electromagnetic wave
      propagation in photonic time crystal and photonic space-time crystal, the
      simulation results show that more intensive scatter fields can obtained in
      photonic time crystal and photonic space-time crystal.

PMID- 29215042
TI  - A PLAG1 mutation contributed to stature recovery in modern cattle.
AB  - The recent evolution of cattle is marked by fluctuations in body size. Height in
      the Bos taurus lineage was reduced by a factor of ~1.5 from the Neolithic to the
      Middle Ages, and increased again only during the Early Modern Ages. Using
      haplotype analysis, we found evidence that the bovine PLAG1 mutation (Q) with
      major effects on body size, weight and reproduction is a >1,000 years old derived
      allele that increased rapidly in frequency in Northwestern European B. taurus
      between the 16th and 18th centuries. Towards the 19th and 20th centuries, Q was
      introgressed into non-European B. taurus and Bos indicus breeds. These data
      implicate a major role of Q in recent changes in body size in modern cattle, and
      represent one of the first examples of a genomic sweep in livestock that was
      driven by selection on a complex trait.

PMID- 29215045
TI  - Auditory closed-loop stimulation of EEG slow oscillations strengthens sleep and
      signs of its immune-supportive function.
AB  - Sleep is essential for health. Slow wave sleep (SWS), the deepest sleep stage
      hallmarked by electroencephalographic slow oscillations (SOs), appears of
      particular relevance here. SWS is associated with a unique endocrine milieu
      comprising minimum cortisol and high aldosterone, growth hormone (GH), and
      prolactin levels, thereby presumably fostering efficient adaptive immune
      responses. Yet, whether SWS causes these changes is unclear. Here we enhance SOs
      in men by auditory closed-loop stimulation, i.e., by delivering tones in
      synchrony with endogenous SOs. Stimulation intensifies the hormonal milieu
      characterizing SWS (mainly by further reducing cortisol and increasing
      aldosterone levels) and reduces T and B cell counts, likely reflecting a
      redistribution of these cells to lymphoid tissues. GH remains unchanged. In
      conclusion, closed-loop stimulation of SOs is an easy-to-use tool for probing SWS
      functions, and might also bear the potential to ameliorate conditions like
      depression and aging, where disturbed sleep coalesces with specific hormonal and
      immunological dysregulations.

PMID- 29215046
TI  - Rapid and effective enrichment of mononuclear cells from blood using
      acoustophoresis.
AB  - Effective separation methods for fractionating blood components are needed for
      numerous diagnostic and research applications. This paper presents the use of
      acoustophoresis, an ultrasound based microfluidic separation technology, for
      label-free, gentle and continuous separation of mononuclear cells (MNCs) from
      diluted whole blood. Red blood cells (RBCs) and MNCs behave similar in an
      acoustic standing wave field, compromising acoustic separation of MNC from RBC in
      standard buffer systems. However, by optimizing the buffer conditions and thereby
      changing the acoustophoretic mobility of the cells, we were able to enrich MNCs
      relative to RBCs by a factor of 2,800 with MNC recoveries up to 88%. The
      acoustophoretic microchip can perform cell separation at a processing rate of
      more than 1 * 105 cells/s, corresponding to 5 ul/min undiluted whole blood
      equivalent. Thus, acoustophoresis can be easily integrated with further down
      stream applications such as flow cytometry, making it a superior alternative to
      existing MNC isolation techniques.

PMID- 29215047
TI  - Harvesting energy from low-frequency excitations through alternate contacts
      between water and two dielectric materials.
AB  - Recent studies have demonstrated the benefits of water-dielectric interfaces in
      electrostatic energy harvesting. Most efforts have been focused on extracting the
      kinetic energy from the motions of water drops on hydrophobic surfaces, and thus,
      the resulting schemes inherently prefer cases where the water drops move at a
      high speed, or vibrate at a high frequency. Here we report a method for directly
      harvesting ambient mechanical energy as electric potential energy through water
      droplets by making alternate contacts with CYTOP and PTFE thin films. Because
      CYTOP and PTFE acquire significantly different surface charge densities during
      contact with water, such a difference can be utilized to effectively generate
      electricity. We demonstrate this concept using prototype devices fabricated on
      silicon substrates with a simple procedure. In the experiments conducted, a water
      drop of 400 MUL alone could generate a peak open-circuit voltage of 42 V under a
      0.25 Hz vibration. Under a 2.5 Hz vibration, the peak open-circuit voltage
      reached 115 V under an external bias of 8 V. The demonstrated efficiency is
      orders of magnitude higher than those of existing devices of similar dimensions.

PMID- 29215049
TI  - STR profiling and Copy Number Variation analysis on single, preserved cells using
      current Whole Genome Amplification methods.
AB  - The growing interest in liquid biopsies for cancer research and cell-based non
      invasive prenatal testing (NIPT) invigorates the need for improved single cell
      analysis. In these applications, target cells are extremely rare and fragile in
      peripheral circulation, which makes the genetic analysis very challenging. To
      overcome these challenges, cell stabilization and unbiased whole genome
      amplification are required. This study investigates the performance of four WGA
      methods on single or a limited number of cells after 24 hour of Streck Cell-Free
      DNA BCT preservation. The suitability of the DNA, amplified with Ampli1, DOPlify,
      PicoPLEX and REPLI-g, was assessed for both short tandem repeat (STR) profiling
      and copy number variant (CNV) analysis after shallow whole genome massively
      parallel sequencing (MPS). Results demonstrate that Ampli1, DOPlify and PicoPLEX
      perform well for both applications, with some differences between the methods.
      Samples amplified with REPLI-g did not result in suitable STR or CNV profiles,
      indicating that this WGA method is not able to generate high quality DNA after
      Streck Cell-Free DNA BCT stabilization of the cells.

PMID- 29215048
TI  - High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis:
      Mechanisms and a Phase I/IIa study.
AB  - Pancreatic cancer is among the most lethal cancers with poorly tolerated
      treatments. There is increasing interest in using high-dose intravenous ascorbate
      (IVC) in treating this disease partially because of its low toxicity. IVC
      bypasses bioavailability barriers of oral ingestion, provides pharmacological
      concentrations in tissues, and exhibits selective cytotoxic effects in cancer
      cells through peroxide formation. Here, we further revealed its anti-pancreatic
      cancer mechanisms and conducted a phase I/IIa study to investigate
      pharmacokinetic interaction between IVC and gemcitabine. Pharmacological
      ascorbate induced cell death in pancreatic cancer cells with diverse mutational
      backgrounds. Pharmacological ascorbate depleted cellular NAD+ preferentially in
      cancer cells versus normal cells, leading to depletion of ATP and robustly
      increased alpha-tubulin acetylation in cancer cells. While ATP depletion led to
      cell death, over-acetylated tubulin led to inhibition of motility and mitosis.
      Collagen was increased, and cancer cell epithelial-mesenchymal transition (EMT)
      was inhibited, accompanied with inhibition in metastasis. IVC was safe in
      patients and showed the possibility to prolong patient survival. There was no
      interference to gemcitabine pharmacokinetics by IVC administration. Taken
      together, these data revealed a multi-targeting mechanism of pharmacological
      ascorbate's anti-cancer action, with minimal toxicity, and provided guidance to
      design larger definitive trials testing efficacy of IVC in treating advanced
      pancreatic cancer.

PMID- 29215050
TI  - Tumor necrosis factor-alpha regulates photoreceptor cell autophagy after retinal
      detachment.
AB  - Photoreceptor cell death is the ultimate process underlying many retinal
      diseases, including retinal detachment (RD). Both autophagy and inflammatory
      factors, such as tumor necrosis factor-alpha (TNF-alpha), participate in
      photoreceptor cell death after RD. In this study, we examined whether TNF-alpha
      inhibition would impact the autophagy of photoreceptors and reduce the death of
      photoreceptors after retinal detachment (RD). RD models were created in C57BL/6J
      mice by a subretinal injection of 1% hyaluronic acid. The TNF-alpha inhibitor
      infliximab was administered via intraperitoneal injection two hours before RD.
      The levels of TNF-alpha and the autophagy-related proteins Atg5 and LC3B were
      assayed by immunofluorescence at 1 day, 3 days, and 7 days following RD.
      Apoptosis was examined at 3 days post-detachment via TUNEL assays. Photoreceptor
      cell counts were assessed at 7 days after RD. After RD, the protein levels of
      LC3B and Atg5 increased and reached a peak at 3 days, which decreased at 7 days.
      The expression of LC3B and Atg5 was prolonged and increased at a slower rate with
      TNF-alpha inhibition. The moderate augmentation and extension of autophagy
      through TNF-alpha inhibition resulted in the reduction of apoptosis and the
      enhancement of photoreceptor cell survival.

PMID- 29215051
TI  - A web-based GPS system for displacement monitoring and failure mechanism analysis
      of reservoir landslide.
AB  - It is important to monitor the displacement time series and to explore the
      failure mechanism of reservoir landslide for early warning. Traditionally, it is
      a challenge to monitor the landslide displacements real-timely and automatically.
      Globe Position System (GPS) is considered as the best real-time monitoring
      technology, however, the accuracies of the landslide displacements monitored by
      GPS are not assessed effectively. A web-based GPS system is developed to monitor
      the landslide displacements real-timely and automatically in this study. And the
      discrete wavelet transform (DWT) is proposed to assess the accuracy of the GPS
      monitoring displacements. Wangmiao landslide in Three Gorges Reservoir area in
      China is used as case study. The results show that the web-based GPS system has
      advantages of high precision, real-time, remote control and automation for
      landslide monitoring; the Root Mean Square Errors of the monitoring landslide
      displacements are less than 5 mm. Meanwhile, the results also show that a rapidly
      falling reservoir water level can trigger the reactivation of Wangmiao landslide.
      Heavy rainfall is also an important factor, but not a crucial component.

PMID- 29215052
TI  - Peroxiredoxin activity is a major landmark of male fertility.
AB  - Peroxiredoxins (PRDXs) are important antioxidant enzymes reported to have a role
      in sperm function and male fertility. However, how PRDXs affects male fertility
      remain fundamental unanswered questions. We therefore sought to investigate the
      role of these enzymes in sperm function and fertilisation. In this in vitro
      trial, mouse spermatozoa were incubated with different concentrations of conoidin
      A (1, 10, or 100 uM), a specific inhibitor of PRDXs. Our results demonstrated
      that inhibition of PRDXs by conoidin A significantly decreased the oxidized form
      of peroxiredoxins (PRDXs-SO3) in spermatozoa. Decreased PRDX activity was
      associated with a significant reduction in sperm motility parameters, viability,
      and intracellular ATP, whereas ROS levels, DNA fragmentation, and loss of
      mitochondrial membrane potential were increased. Simultaneously capacitation and
      the acrosome reaction were also significantly inhibited perhaps as a consequence
      of decreased tyrosine phosphorylation and protein kinase-A activity. In addition,
      fertilisation and early embryonic development were adversely affected following
      PRDXs inhibition in spermatozoa. Taken together, our data demonstrate that
      decreased PRDX activity directly affects male fertility due to negative effects
      on important functions and biochemical properties of spermatozoa, ultimately
      leading to poor fertilisation and embryonic development.

PMID- 29215053
TI  - Selective carbon dioxide sorption and heterogeneous catalysis by a new 3D Zn-MOF
      with nitrogen-rich 1D channels.
AB  - We prepared a new C 2h-symmetric bridging ligand, 3,3'-(pyrazine-2,5
      diyl)dibenzoic acid (3,3'-PDBA), through a Suzuki coupling reaction. 3,3'-PDBA
      contains a central pyrazine ring instead of the phenyl ring of 3,3'
      terphenyldicarboxylic acid (3,3'-TPDC). Despite the geometrical similarity of the
      two bridging ligands, the reaction between Zn(NO3)2.6H2O and 3,3'-PDBA in the
      presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) yielded a structurally
      different Zn-based metal-organic framework (Zn-MOF). The Zn-MOF, [Zn2(3,3'
      PDBA)2(DABCO)1.5].2DMF.H2O, had two-dimensional (2D) layers, and the interlocked
      2D layers formed a porous 3D framework. Interestingly, one of the two available N
      atoms of DABCO remained intact. The uncoordinated N atoms of the dangling DABCO
      ligand and the pyrazinyl N atoms of the 3,3'-PDBA bridging ligand were fully
      exposed toward the 1D channels. Therefore, the 1D channels represented a highly
      nitrogen-rich environment. Gas sorption analysis indicated that the Zn-MOF was
      selective for adsorption of CO2 at 196 K over N2 (77 K) and H2 (77 K). The
      exceptionally high zero surface coverage heat of CO2 adsorption (Q st = 79.5 kJ
      mol-1) was attributable to the openly accessible multiple Lewis basic sites in
      the nitrogen-rich 1D channels. Zn-MOF also showed good Lewis base catalytic
      activities in three model aldol-type reactions with good recyclability due to
      chemically accessible 3 degrees  amine sites.

PMID- 29215054
TI  - In vivo redox metabolic imaging of mitochondria assesses disease progression in
      non-alcoholic steatohepatitis.
AB  - Given the rising incidence of non-alcoholic fatty liver disease (NAFLD) in both
      adults and children, the development of a non-invasive diagnostic method for
      assessing disease progression to non-alcoholic steatohepatitis (NASH) has become
      an important research goal. Currently available non-invasive imaging technologies
      are only able to assess fat accumulation in the liver. Therefore, these methods
      are not suitable for a precise diagnosis of NASH. The standard diagnostic
      technique for NASH, liver biopsy, has several drawbacks, including the higher
      risk of complications that accompanies invasive procedures. Here, we demonstrated
      that in vivo mitochondrial redox metabolism was dramatically altered at an early
      stage, before histopathological changes, and NASH could be accurately diagnosed
      by in vivo dynamic nuclear polarization-magnetic resonance imaging, with
      carbamoyl-PROXYL as a molecular imaging probe. In addition, this technique was
      feasible for the diagnosis of NASH compared with histopathological findings from
      biopsies. Our data reveal a novel method for monitoring the dynamics of redox
      metabolic changes in NAFLD/NASH.

PMID- 29215056
TI  - Experimental nonlocality-based network diagnostics of multipartite entangled
      states.
AB  - We introduce a novel diagnostic scheme for multipartite networks of entangled
      particles, aimed at assessing the quality of the gates used for the engineering
      of their state. Using the information gathered from a set of suitably chosen
      multiparticle Bell tests, we identify conditions bounding the quality of the
      entangled bonds among the elements of a register. We illustrate the effectiveness
      of our proposal by characterizing a quantum resource engineered combining two
      photon hyperentanglement and photonic-chip technology. Our approach opens up
      future studies on medium-sized networks due to the intrinsically modular nature
      of cluster states, and paves the way to section-by-section analysis of larger
      photonics resources.

PMID- 29215055
TI  - Impairing the function of MLCK, myosin Va or myosin Vb disrupts Rhinovirus B14
      replication.
AB  - Together, the three human rhinovirus (RV) species are the most frequent cause of
      the common cold. Because of their high similarity with other viral species of the
      genus Enterovirus, within the large family Picornaviridae, studies on RV
      infectious activities often offer a less pathogenic model for more aggressive
      enteroviruses, e.g. poliovirus or EV71. Picornaviruses enter via receptor
      mediated endocytosis and replicate in the cytosol. Most of them depend on
      functional F-actin, Rab proteins, and probably motor proteins. To assess the
      latter, we evaluated the role of myosin light chain kinase (MLCK) and two myosin
      V isoforms (Va and Vb) in RV-B14 infection. We report that ML-9, a very specific
      MLCK inhibitor, dramatically reduced RV-B14 entry. We also demonstrate that RV
      B14 infection in cells expressing dominant-negative forms of myosin Va and Vb was
      impaired after virus entry. Using immunofluorescent localization and
      immunoprecipitation, we show that myosin Va co-localized with RV-B14 exclusively
      after viral entry (15 min post infection) and that myosin Vb was present in the
      clusters of newly synthesized RNA in infected cells. These clusters, observed at
      180 min post infection, are reminiscent of replication sites. Taken together,
      these results identify myosin light chain kinase, myosin Va and myosin Vb as new
      players in RV-B14 infection that participate directly or indirectly in different
      stages of the viral cycle.

PMID- 29215057
TI  - Mechanochemical mineralization of "very persistent" fluorocarbon surfactants -
      6:2 fluorotelomer sulfonate (6:2FTS) as an example.
AB  - Fluorinated organic chemicals have a wide variety of industrial and consumer
      applications. For long time perfluorooctane sulfonate and perfluorooctanoic acid
      have been used as precursors for manufacture of such chemicals. However, these C8
      chain compounds have been demonstrated to be toxic, persistent, and
      bioaccumulative, thus inducing their phase-out. Currently, C6 telomer based
      fluorocarbon surfactants are considered better alternatives to C8 products
      because of their low bioaccumulability. But, their high persistency suggests that
      in the near future their concentrations will increase in the environment and in
      industrial waste. Being a solid state non-thermal technology, mechanochemical
      treatment is a good candidate for the destruction of emerging C6 fluorotelomers
      in solid waste. In the present study, 6:2 fluorotelomer sulfonate is effectively
      destroyed (~100%) in rapid manner (<1 h) by high energy ball milling with KOH.
      Stoichiometric fluoride formation confirms its entire mineralization, assuring
      that no toxic by-products are generated. Reaction mechanism and kinetics indicate
      that effective mineralization of the perfluorinated moiety is obtained thanks to
      a rapid CF2 "flake-off" process through radical mechanism.

PMID- 29215058
TI  - Hybrid black silicon solar cells textured with the interplay of copper-induced
      galvanic displacement.
AB  - Metal-assisted chemical etching (MaCE) has been widely employed for the
      fabrication of regular silicon (Si) nanowire arrays. These features were
      originated from the directional etching of Si preferentially along <100>
      orientations through the catalytic assistance of metals, which could be gold,
      silver, platinum or palladium. In this study, the dramatic modulation of etching
      profiles toward pyramidal architectures was undertaken by utilizing copper as
      catalysts through a facile one-step etching process, which paved the exceptional
      way on the texturization of Si for advanced photovoltaic applications. Detailed
      examinations of morphological evolutions, etching kinetics and formation
      mechanism were performed, validating the distinct etching model on Si contributed
      from cycling reactions of copper deposition and dissolution under a quasi-stable
      balance. In addition, impacts of surface texturization on the photovoltaic
      performance of organic/inorganic hybrid solar cells were revealed through the
      spatial characterizations of voltage fluctuations upon light mapping analysis. It
      was found that the pyramidal textures made by copper-induced cycling reactions
      exhibited the sound antireflection characteristics, and further achieved the
      leading conversion efficiency of 10.7%, approximately 1.8 times and beyond 1.2
      times greater than that of untexturized and nanowire-based solar cells,
      respectively.

PMID- 29215060
TI  - Removal of sulfur by adding zinc during the digestion process of high-sulfur
      bauxite.
AB  - This paper proposes a novel approach to sulfur removal by adding zinc during the
      digestion process. The effects of zinc dosage on the concentrations of different
      valence sulfur in sodium aluminate solution were investigated at length to find
      that high-valence sulfur (S2O32-, SO32-, SO42-) concentration in sodium aluminate
      solution decreases, but the concentration of the S2- in the sodium aluminate
      solution increases as zinc dosage increases. This suggests that zinc can react
      with high-valence sulfur to generate S2- at digestion temperature, which is
      consistent with our thermodynamic calculation results. In this study, as zinc
      dosage increases, sulfur digestion rate decreases while sulfur content in red mud
      markedly increases when zinc dosage was below 4%; the digestion rates of sulfur
      and sulfur content in red mud remains stable when zinc dosage was above 4%; the
      alumina digestion rate, conversely, increased slightly throughout the experiment.
      This suggests that high-valence sulfur in sodium aluminate solution can be
      converted to S2- and then enter red mud to be removed completely by adding zinc
      during the digestion process.

PMID- 29215059
TI  - Protective effect of mesenchymal stem cells on the pressure ulcer formation by
      the regulation of oxidative and endoplasmic reticulum stress.
AB  - Cutaneous ischemia-reperfusion (I/R) injury is associated with the early
      pathogenesis of cutaneous pressure ulcers (PUs). The objective of this study was
      to investigate the effect of mesenchymal stem cells (MSCs) injection on the
      formation of PUs after I/R injury and determine the underlying mechanisms. We
      found that the subcutaneous injection of MSCs into areas of I/R injured skin
      significantly suppressed the formation of PUs. I/R-induced vascular damage,
      hypoxia, oxidative DNA damage, and apoptosis were decreased by MSCs injection.
      Oxidative stress signals detected after I/R in OKD48 (Keap1-dependent oxidative
      stress detector, No-48-luciferase) mice were decreased by the injection of MSCs.
      In cultured fibroblasts, MSCs-conditioned medium significantly inhibited oxidant
      induced reactive oxygen species (ROS) generation and apoptosis. Furthermore,
      endoplasmic reticulum (ER) stress signals detected after I/R in ERAI (ER stress
      activated indicator) mice were also decreased by the injection of MSCs. These
      results suggest that the injection of MSCs might protect against the development
      of PUs after cutaneous I/R injury by reducing vascular damage, oxidative cellular
      damage, oxidative stress, ER stress, and apoptosis.

PMID- 29215061
TI  - Local Production of Activated Factor X in Atherosclerotic Plaque Induced Vascular
      Smooth Muscle Cell Senescence.
AB  - Our previous study demonstrated that coagulation factor Xa (FXa) induced
      endothelial cell senescence, resulting in inflammation and impaired angiogenesis.
      This mechanism is dictated through protease-activated receptors, PARs, insulin
      like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs
      contributes to the pathophysiology of several chronic inflammatory diseases,
      including atherosclerosis. Thus, we speculated that similar mechanism might
      participate in the progression of atherosclerotic plaques. In the present study,
      we successfully identified the cells that produced FX/Xa in atherosclerosis using
      human atherosclerotic plaques obtained from carotid endarterectomy. In situ
      hybridization for FX revealed that FX was generated in vascular smooth muscle
      cells (VSMC), inflammatory cells, and endothelial cells. Then, we examined the
      effects of FXa on the growth of VSMC in vitro. The present study revealed that
      chronic FXa stimulation significantly induced the senescence of VSMC with
      concomitant upregulation of IGFBP-5 and p53. Inhibition of FXa signaling with
      rivaroxaban or knock down of IGFBP-5 significantly reduced FXa-induced VSMC
      senescence and inflammatory cytokine production. Finally, we confirmed that FXa
      and IGFBP-5 are co-distributed in atherosclerotic plaques. In conclusion,
      induction of senescence of VSMC induced by locally produced FX/Xa may contribute
      to the progression of atherosclerosis.

PMID- 29215062
TI  - Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide
      Inhibitors of Influenza Virus Endonuclease.
AB  - Influenza is a serious hazard to human health that causes hundreds of thousands
      of deaths annually. Though vaccines and current therapeutics can blunt some of
      the perilous impact of this viral infection, new treatments are needed due to the
      constantly evolving nature of this virus. Recently, our growing understanding of
      an essential influenza viral protein, PA, has led to the development of focused
      libraries of new small molecules that specifically target the active site of the
      PA influenza endonuclease, which we report here. Our overarching approach has
      been to proactively develop lead inhibitors that are less likely to rapidly
      develop clinical resistance by optimizing inhibitors that retain activity against
      induced resistant mutants. Here, we report details behind the discovery of new
      potent inhibitors of wild type and resistant mutant endonucleases along with
      their high-resolution co-crystal structure-activity relationships. These results
      add to our understanding of nuclease protein targets and potentially serve as
      starting points for a new therapeutic approach to the treatment of influenza.

PMID- 29215063
TI  - Reduced vertical displacement of the center of mass is not accompanied by reduced
      oxygen uptake during walking.
AB  - The six determinants of gait proposed that the goal of gait is to minimize
      vertical displacement of the body's center of mass (CoM) with the objective to
      optimize energy expenditure. On the contrary, recent investigations suggest that
      reduced vertical displacement leads to an increase in energy expenditure.
      However, these investigations had the included subjects deliberately changing
      their gait, which could bias the endpoint measures. The present study
      investigated the effect of reduced vertical displacement of the CoM on oxygen
      uptake and walking economy without imposing altered gait patterns. This was
      accomplished by having subjects walk on a curved treadmill and on a flat
      treadmill. Vertical displacement of the CoM (sacrum marker displacement), oxygen
      uptake, walking economy, stride characteristics and lower limb joint angles were
      measured. There were significant differences in stride characteristics and phase
      dependent differences in lower limb movement pattern between the two conditions
      which in size were comparable to the changes observed between different speeds.
      The vertical displacement of the CoM was significantly reduced on the curved
      treadmill. This was accompanied by an increase in oxygen uptake and walking
      economy. These results support recent assertions that the six determinants of
      gait do not serve to improve walking economy.

PMID- 29215064
TI  - Self-adaptive Bioinspired Hummingbird-wing Stimulated Triboelectric
      Nanogenerators.
AB  - Bio-inspired technologies have remarkable potential for energy harvesting from
      clean and sustainable energy sources. Inspired by the hummingbird-wing structure,
      we propose a shape-adaptive, lightweight triboelectric nanogenerator (TENG)
      designed to exploit the unique flutter mechanics of the hummingbird for small
      scale wind energy harvesting. The flutter is confined between two surfaces for
      contact electrification upon oscillation. We investigate the flutter mechanics on
      multiple contact surfaces with several free-standing and lightweight
      electrification designs. The flutter driven-TENGs are deposited on simplified
      wing designs to match the electrical performance with variations in wind speed.
      The hummingbird TENG (H-TENG) device weighed 10 g, making it one of the lightest
      TENG harvesters in the literature. With a six TENG network, the hybrid design
      attained a 1.5 W m-2 peak electrical output at 7.5 m/s wind speed with an
      approximately linear increase in charge rate with the increased number of TENG
      harvesters. We demonstrate the ability of the H-TENG networks to operate Internet
      of Things (IoT) devices from sustainable and renewable energy sources.

PMID- 29215065
TI  - Toll-like Receptor Activation Induces Degeneration of Human Intervertebral Discs.
AB  - Toll-like receptors (TLR) are activated by endogenous alarmins such as fragmented
      extracellular matrix compounds found in the degenerating disc. TLRs regulate
      cytokine, neurotrophin, and protease expression in human disc cells in vitro, and
      thus control key factors in disc degeneration. However, whether TLR activation
      leads to degenerative changes in intact human discs is unclear. Nucleus pulposus
      (NP) cells isolated from non-degenerating discs increase IL-1beta and nerve
      growth factor gene expression following treatment with Pam2CSK4 (TLR2/6 agonist)
      but not Pam3CSK4 (TLR1/2 agonist). Challenging NP cells with Pam2CSK4 or 30 kDa
      fibronectin fragments (FN-f, an endogenous TLR2 and TLR4 alarmin) increased
      secretion of proinflammatory cytokines. We then investigated the effect of TLR
      activation in intact, non-degenerate, ex vivo human discs. Discs were injected
      with PBS, Pam2CSK4 and FN-f, and cultured for 28 days. TLR activation increased
      proteoglycan and ECM protein release into the culture media and decreased
      proteoglycan content in the NP. Proteases, including MMP3, 13 and HTRA1, are
      secreted at higher levels following TLR activation. In addition, proinflammatory
      cytokine levels, including IL-6, TNFalpha and IFNgamma, increased following TLR
      activation. These results indicate that TLR activation induces degeneration in
      human discs. Therefore, TLRs are potential disease-modifying therapeutic targets
      to slow disc degeneration.

PMID- 29215066
TI  - Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits
      turnover and reduces fibrosis in dystrophic muscle.
AB  - Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is
      fatal. DMD patients lack the expression of the structural protein dystrophin
      caused by mutations within the DMD gene. The absence of functional dystrophin
      protein results in excessive damage from normal muscle use due to the compromised
      structural integrity of the dystrophin associated glycoprotein complex. As a
      result, DMD patients exhibit ongoing cycles of muscle destruction and
      regeneration that promote inflammation, fibrosis, mitochondrial dysfunction,
      satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function.
      The nuclear receptor REV-ERB suppresses myoblast differentiation and recently we
      have demonstrated that the REV-ERB antagonist, SR8278, stimulates muscle
      regeneration after acute injury. Therefore, we decided to explore whether the REV
      ERB antagonist SR8278 could slow the progression of muscular dystrophy. In mdx
      mice SR8278 increased lean mass and muscle function, and decreased muscle
      fibrosis and muscle protein degradation. Interestingly, we also found that SR8278
      increased the SC pool through stimulation of Notch and Wnt signaling. These
      results suggest that REV-ERB is a potent target for the treatment of DMD.

PMID- 29215069
TI  - Topological gapless phase in Kitaev model on square lattice.
AB  - We study the topological feature of gapless states in the fermionic Kitaev model
      on a square lattice. There are two types of gapless states which are
      topologically trivial and nontrivial. We show that the topological gapless phase
      lives in a wide two-dimensional parameter region and are characterized by two
      vertices of an auxiliary vector field de-fined in the two-dimensional momentum
      space, with opposite winding numbers. The isolated band touching points, as the
      topological defects of the field, move, emerge, and disappear as the parameters
      vary. The band gap starts to open only at the merg-ing points, associated with
      topologically trivial gapless states. The symmetry protect-ing the topological
      gapless phase and the robustness under perturbations are also discussed.

PMID- 29215067
TI  - Profiling invasive Plasmodium falciparum merozoites using an integrated omics
      approach.
AB  - The symptoms of malaria are brought about by blood-stage parasites, which are
      established when merozoites invade human erythrocytes. Our understanding of the
      molecular events that underpin erythrocyte invasion remains hampered by the short
      period of time that merozoites are invasive. To address this challenge, a
      Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was
      developed and investigated. Purified LLMs invaded erythrocytes by an increase of
      10-300 fold compared to wild-type (WT) merozoites. Using an integrated omics
      approach, we investigated the basis for the phenotypic difference. Only a few
      single nucleotide polymorphisms within the P. falciparum genome were identified
      and only marginal differences were observed in the merozoite transcriptomes. By
      contrast, using label-free quantitative mass-spectrometry, a significant change
      in protein abundance was noted, of which 200 were proteins of unknown function.
      We determined the relative molar abundance of over 1100 proteins in LLMs and
      further characterized the major merozoite surface protein complex. A unique
      processed MSP1 intermediate was identified in LLM but not observed in WT
      suggesting that delayed processing may be important for the observed phenotype.
      This integrated approach has demonstrated the significant role of the merozoite
      proteome during erythrocyte invasion, while identifying numerous unknown proteins
      likely to be involved in invasion.

PMID- 29215068
TI  - Integrated DNA methylome and transcriptome analysis reveals the ethylene-induced
      flowering pathway genes in pineapple.
AB  - Ethylene has long been used to promote flowering in pineapple production.
      Ethylene-induced flowering is dose dependent, with a critical threshold level of
      ethylene response factors needed to trigger flowering. The mechanism of ethylene
      induced flowering is still unclear. Here, we integrated isoform sequencing (iso
      seq), Illumina short-reads sequencing and whole-genome bisulfite sequencing
      (WGBS) to explore the early changes of transcriptomic and DNA methylation in
      pineapple following high-concentration ethylene (HE) and low-concentration
      ethylene (LE) treatment. Iso-seq produced 122,338 transcripts, including 26,893
      alternative splicing isoforms, 8,090 novel transcripts and 12,536 candidate long
      non-coding RNAs. The WGBS results suggested a decrease in CG methylation and
      increase in CHH methylation following HE treatment. The LE and HE treatments
      induced drastic changes in transcriptome and DNA methylome, with LE inducing the
      initial response to flower induction and HE inducing the subsequent response. The
      dose-dependent induction of FLOWERING LOCUS T-like genes (FTLs) may have
      contributed to dose-dependent flowering induction in pineapple by ethylene.
      Alterations in DNA methylation, lncRNAs and multiple genes may be involved in the
      regulation of FTLs. Our data provided a landscape of the transcriptome and DNA
      methylome and revealed a candidate network that regulates flowering time in
      pineapple, which may promote further studies.

PMID- 29215070
TI  - Evolutionary analysis of mumps viruses of genotype F collected in mainland China
      in 2001-2015.
AB  - Mumps incidence in mainland China remains at a high level. Genotype F has been
      the predominant genotype of mumps virus (MuV) in the last 20 years in mainland
      China. To better understand the genetic characteristics of MuV in China, the
      sequences of the Small Hydrophobic (SH), Hemagglutinin-Neuraminidase (HN) and
      Fusion (F) genes of MuVs of genotype F collected during 2001-2015 were
      determined. The evolutionary rates of the HN and F genes were similar (0.5 * 10-3
      substitutions/site/year) whereas the SH gene evolutionary rate was three times
      faster. The most recent common ancestor of genotype F was traced back to 1980.
      Four lineages were identified within HN and F MuV sequences. A phylogeographic
      analysis indicated that the genotype F viruses originally spread from the
      Liaoning and Shandong provinces followed by a spread to the South and East of
      China. This study provides important genetic baseline data for the development of
      prevention and control measures of mumps.

PMID- 29215071
TI  - Damage of the right dorsal superior longitudinal fascicle by awake surgery for
      glioma causes persistent visuospatial dysfunction.
AB  - Patients with glioma frequently present with neuropsychological deficits
      preoperatively and/or postoperatively, and these deficits may remain after the
      chronic phase. However, little is known about postoperative recovery course of
      right hemispheric function. We therefore studied the characteristics and causes
      of persistent cognitive dysfunction in right cerebral hemispheric glioma.
      Eighteen patients who underwent awake surgery participated in this study. All
      patients who received preoperative neuropsychological examinations were assigned
      to two groups according to their test results: preoperative deficit and normal.
      They were reassessed 1 week and 3 months after surgery. The rates of remaining
      deficits in the deficit group at chronic phase were higher than those of the
      normal group for all functions. Despite preoperative normal function, the
      remaining rate for visuospatial cognitive deficits was the highest among all
      functions. The voxel-based lesion-symptom mapping analysis for visuospatial
      cognition revealed that a part of the medial superior and middle frontal gyri
      were resected with high probability in patients with low visuospatial cognitive
      accuracy. Our study indicates that in patients with preoperative
      neuropsychological deficits, these deficits tend to remain until the chronic
      phase. Visuospatial dysfunction frequently persists until the chronic phase,
      which might reflect damage to the superior longitudinal fasciclus I and II.

PMID- 29215072
TI  - Lactation has persistent effects on a mother's metabolism and mitochondrial
      function.
AB  - Human epidemiological data show that breastfeeding reduces the prevalence of
      numerous diseases compared to mothers that give birth but do not participate in
      lactation. The goal of this study was to determine if differences in metabolism,
      mitochondrial function, and oxidative stress underlie the protective phenotype
      found in lactating women. Ten-week old female Sprague-Dawley rats were divided
      into three groups (n = 8 per group): 1) rats that did not reproduce (NR), 2) rats
      that were allowed to mate and become pregnant but did not suckle their pups after
      giving birth (NL), and 3) rats that were allowed to mate and become pregnant and
      suckled their pups for 21 days before weaning (L). All animals were sacrificed at
      approximately 7 months of age, a time corresponding to 15 weeks after the NL and
      L females gave birth. Liver mitochondrial respiration was higher in L rats when
      using NADH-linked substrates and these rats had lower serum glucose
      concentration. Additionally, the L group exhibited changes in liver, skeletal
      muscle, and white adipose tissue PPARdelta protein levels that may, in part,
      explain the observed lower serum glucose concentration. These novel animal
      findings provide evidence of differences in metabolic processes that persist
      months after weaning.

PMID- 29215073
TI  - Solution structure of the major fish allergen parvalbumin Sco j 1 derived from
      the Pacific mackerel.
AB  - Although fish is an important part of the human diet, it is also a common source
      of food allergy. The major allergen in fish is parvalbumin, a well-conserved Ca2+
      binding protein found in the white muscle of many fish species. Here, we studied
      the solution structure of the parvalbumin Sco j 1, derived from the Pacific
      mackerel, using nuclear magnetic resonance spectroscopy. We mapped the IgE
      binding epitope proposed in a recent study onto the present structure.
      Interestingly, three of four residues, which were elucidated as key residues of
      the IgE-binding epitope, were exposed to solvent, whereas one residue faced the
      inside of the molecule. We expect that this solution structure can be used in
      future studies attempting to analyze the various IgE-binding modes of these
      allergens.

PMID- 29215074
TI  - Structural analysis of the complex between influenza B nucleoprotein and human
      importin-alpha.
AB  - Influenza viruses are negative strand RNA viruses that replicate in the nucleus
      of the cell. The viral nucleoprotein (NP) is the major component of the viral
      ribonucleoprotein. In this paper we show that the NP of influenza B has a long N
      terminal tail of 70 residues with intrinsic flexibility. This tail contains the
      Nuclear Location Signal (NLS). The nuclear trafficking of the viral components
      mobilizes cellular import factors at different stages, making these host-pathogen
      interactions promising targets for new therapeutics. NP is imported into the
      nucleus by the importin-alpha/beta pathway, through a direct interaction with
      importin-alpha isoforms. Here we provide a combined nuclear magnetic resonance
      and small-angle X-ray scattering (NMR/SAXS) analysis to describe the dynamics of
      the interaction between influenza B NP and the human importin-alpha. The NP of
      influenza B does not have a single NLS nor a bipartite NLS but our results
      suggest that the tail harbors several adjacent NLS sequences, located between
      residues 30 and 71.

PMID- 29215075
TI  - Optimal pre-plant irrigation and fertilization can improve biomass accumulation
      by maintaining the root and leaf productive capacity of cotton crop.
AB  - Cotton is a major cash crop grown worldwide primarily for fiber and oil seed. As
      the most important cultural practices for cotton production, single pre-plant
      irrigation and basal fertilization for cotton plant growth and yield are well
      documented, but their coupling effects are poorly understood in arid regions. A 2
      year outdoor pot trial was conducted to unravel the effects of pre-plant
      irrigation and basal fertilization on leaf area, root growth, biomass
      accumulation, and capacity of leaf area and root in cotton plant. Two pre-plant
      irrigations (i.e., W80, well-watered and W0, not watered) and two basal dressing
      fertilizations (F10, surface application and F30, deep application) were used in
      the experiments. The aboveground and reproductive biomass were highest in W80F10
      after 69 days after emergence. Furthermore, W80F10 increased the root length in
      the 0-40 cm soil layer and the leaf area and improved the loading boll capacity
      of the effective root length and leaf area. The effective root length and leaf
      area had substantial direct effects on the aboveground and root biomass,
      respectively. Our data suggest that basal fertilizer surface application under
      adequate pre-plant irrigation is an effective strategy for optimal cotton
      production, which improves the coordination of water-nutrient absorption and
      photosynthetic areas and promotes assimilated distribution to the reproductive
      structures.

PMID- 29215076
TI  - A Novel Electroactive Agarose-Aniline Pentamer Platform as a Potential Candidate
      for Neural Tissue Engineering.
AB  - Neuronal disorder is an important health challenge due to inadequate natural
      regeneration, which has been responded by tissue engineering, particularly with
      conductive materials. A bifunctional electroactive scaffold having agarose
      biodegradable and aniline pentamer (AP) conductive parts was designed that
      exhibits appropriate cell attachment/compatibility, as detected by PC12 cell
      seeding. The developed carboxyl-capped aniline-pentamer improved agarose cell
      adhesion potential, also the conductivity of scaffold was in the order 10-5 S/cm
      reported for cell membrane. Electrochemical impedance spectroscopy was applied to
      plot the Nyquist graph and subsequent construction of the equivalent circuit
      model based on the neural model, exhibiting an appropriate cell signaling and an
      acceptable consistency between the components of the scaffold model with neural
      cell model. The ionic conductivity was also measured; exhibiting an enhanced
      ionic conductivity, but lower activation energy upon a temperature rise. Swelling
      behavior of the sample was measured and compared with pristine agarose; so that
      aniline oligomer due to its hydrophobic nature decreased water uptake.
      Dexamethasone release from the developed electroactive scaffold was assessed
      through voltage-responsive method. Proper voltage-dependent drug release could be
      rationally expected because of controllable action and elimination of chemically
      responsive materials. Altogether, these characteristics recommended the
      agarose/AP biopolymer for neural tissue engineering.

PMID- 29215077
TI  - Magnetic Frustration Driven by Itinerancy in Spinel CoV2O4.
AB  - Localized spins and itinerant electrons rarely coexist in geometrically
      frustrated spinel lattices. They exhibit a complex interplay between localized
      spins and itinerant electrons. In this paper, we study the origin of the unusual
      spin structure of the spinel CoV2O4, which stands at the crossover from
      insulating to itinerant behavior using the first principle calculation and
      neutron diffraction measurement. In contrast to the expected paramagnetism,
      localized spins supported by enhanced exchange couplings are frustrated by the
      effects of delocalized electrons. This frustration produces a non-collinear spin
      state even without orbital orderings and may be responsible for macroscopic spin
      glass behavior. Competing phases can be uncovered by external perturbations such
      as pressure or magnetic field, which enhances the frustration.

PMID- 29215078
TI  - Melanization in response to wounding is ancestral in arthropods and conserved in
      albino cave species.
AB  - Many species adapted to aphotic subterranean habitats have lost all body
      pigmentation. Yet, melanization is an important component of wound healing in
      arthropods. We amputated appendages in a variety of cave-adapted and surface
      dwelling arthropods. A dark clot formed at the site of injury in most species
      tested, including even albino cave-adapted species. The dark coloration of the
      clots was due to melanin deposition. The speed of wound melanization was
      uncorrelated with a difference in metabolic rate between surface and cave
      populations of an amphipod. The chelicerate Limulus polyphemus, all isopod
      crustaceans tested, and the cave shrimp Troglocaris anophthalmus did not melanize
      wounds. The loss of wound melanization in T. anophthalmus was an apomorphy
      associated with adaptation to subterranean habitats, but in isopods it appeared
      to be a symplesiomorphy unrelated to colonization of subterranean habitats. We
      conclude that wound melanization i) is an important part of innate immunity
      because it was present in all major arthropod lineages, ii) is retained in most
      albino cave species, and iii) has been lost several times during arthropod
      evolution, indicating melanization is not an indispensable component of wound
      healing in arthropods.

PMID- 29215079
TI  - Design and synthesis of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazole
      derivatives as colchicine binding site inhibitors.
AB  - A series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazol derivatives
      were designed as potential microtubule targeting agents. The regioselective
      alkylation of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-2H-1,2,3-triazole was
      predicted by computations and confirmed by an unambiguous synthetic route. The
      antiproliferative activity of the synthesized compounds was tested in vitro using
      three human cancer cell lines and some compounds exhibited significant
      antiproliferative activity, which suggested the reasonability of introduction of
      the 1,2,3-triazole fragment. Among them, compound 7p showed highest activity with
      the IC50 values at nanomolar level towards all three cell lines, which were
      comparable to the positive control, CA-4. Tubulin polymerization assay,
      immunofluorescence studies, cell cycle analysis and competitive tubulin-binding
      assay strongly proved that 7p is a colchicine binding site inhibitor of tubulin.
      Thus, 7p was identified as a promising drug candidate for further development of
      colchicine binding site inhibitors.

PMID- 29215080
TI  - Risk, Predictors, and Outcomes of Acute Kidney Injury in Patients Admitted to
      Intensive Care Units in Egypt.
AB  - Epidemiology of acute kidney injury (AKI) in developing countries is under
      studied. We evaluated the risk and prognosis of AKI in patients admitted to
      intensive care units (ICUs) in Egypt. We recruited consecutive adults admitted to
      ICUs in Alexandria Teaching Hospitals over six months. We used the KDIGO criteria
      for AKI. We followed participants until the earliest of ICU discharge, death, day
      30 from entry or study end. Of the 532 participants (median age 45 (Interquartile
      range [IQR]: 30-62) years, 41.7% male, 23.7% diabetics), 39.6% had AKI at ICU
      admission and 37.4% developed AKI after 24 hours of ICU admission. Previous need
      of diuretics, sepsis and low education were associated with AKI at ICU admission;
      APACHE II score independently predicted AKI after ICU admission. A total of 120
      (22.6%) patients died during 30-day follow-up. Compared to patients who remained
      AKI-free, mortality was significantly higher in patients who had AKI at study
      entry (Hazard Ratio [HR] 2.14; 95% Confidence Interval [CI] 1.02-4.48) or
      developed AKI in ICU (HR 2.74; 95% CI 1.45-5.17). The risk of AKI is high in
      critically ill people and predicts poor outcomes. Further studies are needed to
      estimate the burden of AKI among patients before ICU admission.

PMID- 29215081
TI  - Experimental Zika Virus Inoculation in a New World Monkey Model Reproduces Key
      Features of the Human Infection.
AB  - A monkey model of Zika virus (ZIKV) infection is urgently needed to better
      understand transmission and pathogenesis, given its proven association with fetal
      brain defects in pregnant women and acute neurological illness. Here we
      experimentally infected 4 male marmosets with ZIKV (prototype 1947 African
      strain) and monitored them clinically with sampling of various body fluids and
      tissues for nearly 3 months. We show that the course of acute infection with ZIKV
      in these New World monkeys resembles the human illness in many respects,
      including (1) lack of apparent clinical symptoms in most cases, (2) persistence
      of the virus in body fluids such as semen and saliva for longer periods of time
      than in serum, and (3) generation of neutralizing antibodies as well as an
      antiviral immunological host response. Importantly, ZIKV-infected saliva samples
      (in addition to serum) were found to be infectious, suggesting potential capacity
      for viral transmission by the oral route. Re-challenge of a previously infected
      marmoset with a contemporary outbreak strain SPH2015 from Brazil resulted in
      continued protection against infection, no viral shedding, and boosting of the
      immune response. Given the key similarities to human infection, a marmoset model
      of ZIKV infection may be useful for testing of new drugs and vaccines.

PMID- 29215082
TI  - The myokinetic control interface: tracking implanted magnets as a means for
      prosthetic control.
AB  - Upper limb amputation deprives individuals of their innate ability to manipulate
      objects. Such disability can be restored with a robotic prosthesis linked to the
      brain by a human-machine interface (HMI) capable of decoding voluntary
      intentions, and sending motor commands to the prosthesis. Clinical or research
      HMIs rely on the interpretation of electrophysiological signals recorded from the
      muscles. However, the quest for an HMI that allows for arbitrary and
      physiologically appropriate control of dexterous prostheses, is far from being
      completed. Here we propose a new HMI that aims to track the muscles contractions
      with implanted permanent magnets, by means of magnetic field sensors. We called
      this a myokinetic control interface. We present the concept, the features and a
      demonstration of a prototype which exploits six 3-axis sensors to localize four
      magnets implanted in a forearm mockup, for the control of a dexterous hand
      prosthesis. The system proved highly linear (R2 = 0.99) and precise (1%
      repeatability), yet exhibiting short computation delay (45 ms) and limited cross
      talk errors (10% the mean stroke of the magnets). Our results open up promising
      possibilities for amputees, demonstrating the viability of the myokinetic
      approach in implementing direct and simultaneous control over multiple digits of
      an artificial hand.

PMID- 29215083
TI  - Association detection between ordinal trait and rare variants based on adaptive
      combination of P values.
AB  - Next-generation sequencing technology not only presents a new method for the
      detection of human genomic structural variation, but also provides a large number
      of genetic data of rare variants for us. Currently, how to detect association
      between human complex diseases and rare variants using genetical data has
      attracted extensive attention. In the field of medicine, many people's health and
      disease conditions are measured by ordinal response variables, namely, the trait
      value reflects the development stage or severity of a certain condition. However,
      most existing methods to test for association between rare variants and complex
      diseases are designed to deal with dichotomous or quantitative traits.
      Association analysis methods of ordinal traits are relatively fewer, and
      considering ordinal traits as dichotomous and quantitative traits will inevitably
      lose some valuable information in the original data. Therefore, in this paper, we
      extend an existing method of adaptive combination of P values (ADA) and propose a
      new method of association analysis for ordinal trait based on it (called OR-ADA)
      to test for possible association between ordinal trait and rare variants. In our
      method, we establish a cumulative logistic regression model, in which the
      regression coefficients are estimated by the Newton-Raphson algorithm and the
      likelihood ratio test is used to test the association. Through a large number of
      simulation studies and an example, we demonstrate the performance of the new
      method and compare it with several methods. The analysis results show that the OR
      ADA strategy is robust to the signs of effects of causal variants and more
      powerful under many scenarios.

PMID- 29215084
TI  - Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive
      predictive value for gout.
AB  - We investigated the interactions of ALPK1 variants and the loci of ABCG2, SLC2A9,
      and SLC22A12 on gout risk. We conducted two case-control studies. Participants
      were recruited from hospitals (n = 410; 104 gout cases and 306 controls) and
      communities (n = 678; 373 gout cases and 305 controls) in Taiwan. The genotypes
      of ALPK1 (rs11726117 M861T, rs231247 R1084R, and rs231253 3' UTR), ABCG2
      (rs2231142 Q141K and rs2231137 V12M), SLC2A9 (rs3733591 R265H and rs1014290), and
      SLC22A12 (rs3825016 H86H, rs11231825 H142H, and rs475688) were genotyped. Under a
      recessive model, the joint effects of ALPK1 variants and the SNPs rs2231142 of
      ABCG2, rs1014290 of SLC2A9, or rs475688 and rs3825016 of SLC22A12 were associated
      with gout. The rs11726117 [CC] of ALPK1 and rs2231142 [TT] of ABCG2 with the
      sequential addition of the rs1014290 [AA] of SLC2A9 and rs3825016 [CC] of
      SLC22A12 were associated with gout risk (odds ratio (OR): 13.01, 15.11, and 55.00
      and positive predictive value (PPV): 56%, 69%, and 99% in the Han group,
      respectively; OR: 3.76, 5.78, and 12.30 and PPV: 74%, 80%, and 81% in the
      aboriginal group, respectively). Combined exposure to the four high-risk
      genotypes of ALPK1 and the uric-acid-related loci of ABCG2, SLC2A9, and SLC22A12
      was associated with an increased gout risk and a high PPV for gout.

PMID- 29215085
TI  - Mitogenomic diversity and differentiation of the Buryats.
AB  - In this paper we present a results of first comprehensive study of the complete
      mitogenomes in the Buryats with regard to their belonging to the main regional
      (eastern and western Buryats); tribal (Khori, Ekhirid, Bulagad, and Khongodor),
      and ethno-territorial (Aginsk, Alar, Balagansk, Barguzin, Ida, Khorinsk, Kuda,
      Selenga, Verkholensk, Olkhon, Tunka, and Shenehen Buryats) groups. The analysis
      of molecular variation performed using regional, tribal, and ethno-territorial
      divisions of the Buryats showed lack of genetic differentiation at all levels.
      Nonetheless, the complete mitogenome analysis revealed a very high level of
      genetic diversity in the Buryats which is the highest among Siberian populations
      and comparable to that in populations of eastern and western Asia. The AMOVA and
      MDS analyses results imply to a strong genetic similarity between the Buryats and
      eastern Asian populations of Chinese and Japanese, suggesting their origin on the
      basis of common maternal ancestry components. Several new Buryat-specific
      branches of haplogroup G (G2a2a, G2a1i, G2a5a) display signals of dispersals
      dating to 2.6-6.6 kya with a possible origin in eastern Asia, thus testifying
      Bronze Age and Neolithic arrival of ancestral eastern Asian component to the
      South Siberia region.

PMID- 29215086
TI  - Genetic predisposition to infection in a case of atypical hemolytic uremic
      syndrome.
AB  - Most cases of hemolytic uremic syndrome (HUS) are caused by infection with
      enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled
      complement activation are associated with the more severe atypical HUS (aHUS).
      Non-EHEC infections can trigger the disease, however, complement defects
      predisposing to such infections have not yet been studied. We describe a 2-month
      old patient infected with different Gram-negative bacterial species resulting in
      aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant
      R229C was found in complement inhibitor vitronectin. Recombinant mutated
      vitronectin showed enhanced complement inhibition in vitro and may have been a
      predisposing factor for infection. Our work indicates that genetic changes in
      aHUS can not only result in uncontrolled complement activation but also increase
      vulnerability to infections contributing to aHUS.

PMID- 29215087
TI  - Mitochondrial DNA variations in Austronesian-speaking populations living in the
      New Georgia Islands, the Western Province of the Solomon Islands.
AB  - Modern Austronesian (AN)-speaking Melanesians are considered to be derived from
      the admixture of indigenous non-Austronesian (NAN)-speaking people and AN
      speaking people from Southeast Asia. In this study, we analyzed mitochondrial DNA
      (mtDNA) variations in the D-loop region for two AN-speaking Melanesian
      populations (Munda and Kusaghe) and an AN-speaking Micronesian population
      (Rawaki) in the New Georgia Islands, the Western Province of the Solomon Islands
      to examine their genetic similarities to AN-speaking Polynesians in Tonga and NAN
      speaking Melanesians, Gidra, in Papua New Guinea. The 'Polynesian motif', which
      is well-characterized mtDNA marker for Polynesians, was frequently observed in
      Munda and Kusaghe. Of particular interest, haplogroup E1a2 + 16261, which has
      been rarely observed in the Solomon Islands, accounted for 12.8% in Kusaghe. It
      has been reported that the haplogroup E1a2 arose in Island Southeast Asia (ISEA)
      9400 +/- 2850 years ago. Phylogenetic and principle component analyses for 24
      Oceanian populations revealed that Munda and Kusaghe populations were genetically
      close to Tongan population, but not to Gidra. Rawaki population showed no
      apparent genetic similarities to populations of Tonga and Gidra. Our results
      suggest that considerable gene flow from AN-speaking populations originated from
      Southeast Asia to indigenous Melanesians occurred in the New Georgia Islands.

PMID- 29215088
TI  - Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the
      first report of an adult-onset disease.
AB  - Axonal Charcot-Marie-Tooth disease (CMT) is most frequently caused by mutations
      in the MFN2 gene (CMT2A) that can lead to various clinical phenotypes. The age at
      disease onset varies, but most cases occur before adolescence. We report two
      Japanese sisters who presented with middle-age-onset peripheral neuropathy with
      distinct clinical features. In the affected sisters, a homozygous missense
      mutation, c.1894C>T, p.R632W, corresponding to the transmembrane domain of MFN2
      was identified; this mutation was heterozygous in another non-affected sibling,
      demonstrating co-segregation of the genotype and phenotype. The patients
      developed adult-onset slowly progressive muscle weakness that was predominant in
      the calf muscles and sensory disturbance. Magnetic resonance imaging revealed
      diffuse atrophy of the spinal cord, especially in the thoracic segment, and mild
      atrophy of the parietal lobe and the cerebellum in both patients. Electron
      microscopy of the sural nerve revealed clusters of round and swollen
      mitochondria. This is the first case report of adult-onset CMT2A with an
      autosomal-recessive inheritance pattern. The phenotype caused by the MFN2
      mutation in these cases is very mild, considering that the mutation causes middle
      aged-onset Charcot-Marie-Tooth even in the homozygous state. The mechanism of
      MFN2 mutation-induced toxicity is an interesting theme that awaits further
      investigations.

PMID- 29215090
TI  - In vivo genome editing via the HITI method as a tool for gene therapy.
AB  - Using genome-editing technologies to correct specific mutations represents a
      potentially transformative new approach for treating genetic disorders. Despite
      rapid advances in the field of genome editing, it is still unclear whether the
      long-standing goal of in vivo targeted transgene integration is feasible. This is
      primarily because current tools are inefficient. In particular, current
      technologies are incapable of targeted gene knock-in in non-dividing cells, the
      major building blocks of adult tissues. This poses a significant barrier for
      developing therapeutic strategies to treat a broad range of devastating genetic
      disorders. Recently, our group has developed a unique CRISPR/Cas9-based strategy,
      termed homology-independent targeted insertion (HITI), which enables targeted
      gene insertion in non-dividing cells, both in vitro and in vivo. This review will
      summarize current progress in developing this technology, and discuss the
      potential impact of HITI-based gene-correction therapies.

PMID- 29215089
TI  - Genetic analysis of benign familial epilepsies in the first year of life in a
      Chinese cohort.
AB  - Benign familial epilepsies that present themselves in the first year of life
      include benign familial neonatal epilepsy (BFNE), benign familial neonatal
      infantile epilepsy (BFNIE) and benign familial infantile epilepsy (BFIE). We used
      Sanger sequencing and targeted next-generation sequencing to detect gene
      mutations in a Chinese cohort of patients with these three disorders. A total of
      79 families were collected, including 4 BFNE, 7 BFNIE, and 68 BFIE. Genetic
      testing led to the identification of gene mutations in 60 families (60 out of 79,
      75.9%). A total of 42 families had PRRT2 mutations, 9 had KCNQ2 mutations, 8 had
      SCN2A mutations, and 1 had a GABRA6 mutation. In total three of four BFNE
      families were detected with KCNQ2 mutations. Mutations were detected in all BFNIE
      families, including 3 KCNQ2 mutations, 3 SCN2A mutations, and 1 PRRT2 mutation.
      Gene mutations were identified in 50 out of 68 BFIE families (73.5%), including
      41 PRRT2 mutations (41 out of 68, 60.3%), 5 SCN2A mutations, 3 KCNQ2 mutations,
      and 1 GABRA6 mutation. Our results confirmed that mutations in KCNQ2, SCN2A, and
      PRRT2 are major genetic causes of benign familial epilepsy in the first year of
      life in the Chinese population. KCNQ2 is the major gene related to BFNE. PRRT2 is
      the main gene responsible for BFIE.

PMID- 29215091
TI  - Cancer induction and suppression with transcriptional control and epigenome
      editing technologies.
AB  - Cancer epigenetics is one of the most important research subjects in dissecting
      cancer mechanisms and therapeutic targets because the emergence and malignant
      transformation of various cancers are caused by unnatural expression of cancer
      related genes attributed to their epigenetic errors. The original concept of
      cancer epigenetics basically stands on the analysis of the epigenetic status in
      naturally occurring cancer cells; however, the rapidly emerging technology called
      epigenome editing would change this situation drastically. Epigenome editing, the
      most promising derivative technology of genome editing, can modify the epigenetic
      states at the pre-defined genomic locus using the programmable effectors,
      consisting of various epigenetic factors combined with site-specific DNA-binding
      domains. This technology can be utilized in a reversible manner; i.e., cancer
      modeling can be achieved by introducing aberrant epigenetic marks in normal
      cells, and cancer suppression can be achieved by correcting the epigenetic errors
      in cancer cells. In this review, we summarize the basics of epigenome editing and
      cancer epigenetics, followed by the current examples of cancer induction and
      suppression with the transcriptional control and epigenome editing technologies.

PMID- 29215092
TI  - Improvement in the sensitivity of newborn screening for Fabry disease among
      females through the use of a high-throughput and cost-effective method, DNA mass
      spectrometry.
AB  - Many female carriers of Fabry disease are likely to develop severe morbidity and
      mortality. However, by our own estimation, around 80% of female newborns are
      missed by our current enzyme-based screening approach. Our team's aim was to
      develop an improved cost-effective screening method that is able to detect Fabry
      disease among female newborns. In Taiwan, based on a database of 916,000
      newborns, ~98% of Fabry patients carry mutations out of a pool of only 21
      pathogenic mutations. An Agena iPLEX platform was designed to detect these 21
      pathogenic mutations using only a single-assay panel. A total of 54,791 female
      infants were screened and 136 female newborns with the IVS4 + 919G > A mutation
      and one female newborn with the c.656T > C mutation were identified. Using the
      current enzyme-based newborn screening approach as baseline, around 83% of female
      newborns are being missed. Through a family study of the IVS4 female newborns, 30
      IVS4 adult family members were found to have left ventricular hypertrophy. Ten
      patients received endomyocardial biopsy and all were found to have significant
      globotriaosylceramide (Gb3) accumulation in their cardiomyocytes. All of these
      individuals now receive enzyme replacement therapy. We have demonstrated that the
      Agena iPLEX assay is a powerful tool for detecting females with Fabry disease.
      Furthermore, through this screening, we also have been able to identify many
      disease-onset adult family members who were originally undiagnosed for Fabry
      disease. This screening helps them to receive treatment in time before severe and
      irreversible cardiac damage has occurred.

PMID- 29215093
TI  - Two large deletions extending beyond either end of the RHD gene and their red
      cell phenotypes.
AB  - Only two partial deletions longer than 655 nucleotides had been reported for the
      RHD gene, constrained within the gene and causing DEL phenotypes. Using a
      combination of quantitative PCR and long-range PCR, we examined three distinct
      deletions affecting parts of the RHD gene in three blood donors. Their RHD
      nucleotide sequences and exact boundaries of the breakpoint regions were
      determined. DEL phenotypes were caused by a novel 18.4 kb deletion and a
      previously published 5.4 kb deletion of the RHD gene; a D-negative phenotype was
      caused by a novel 7.6 kb deletion. Examination of the deletion-flanking regions
      suggested microhomology-mediated end-joining, replication slippage, and non
      homologous end-joining, respectively, as the most likely mechanisms for the three
      distinct deletions. We described two new deletions affecting parts of the RHD
      gene, much longer than any previously reported partial deletion: one was the
      first deletion observed at the 5' end of the RHD gene extending into the
      intergenic region, and the other the second deletion observed at its 3' end.
      Large deletions present at either end are a mechanism for a much reduced RhD
      protein expression or its complete loss. Exact molecular characterization of such
      deletions is instrumental for accurate RHD genotyping.

PMID- 29215094
TI  - Expression QTL analysis of glaucoma endophenotypes in the Norfolk Island isolate
      provides evidence that immune-related genes are associated with optic disc size.
AB  - Primary open-angle glaucoma (POAG) is influenced by both genetic and
      environmental factors. Despite significant progress in identifying genetic
      variants associated with POAG, there remains a substantial amount of unexplained
      heritability. Study design features that may enhance knowledge of the genetic
      architecture include focusing on multiple quantitative traits related to ocular
      disorders (i.e. endophenotypes), targeting genetic variants that directly
      influence gene expression (i.e. cis-eQTLs) and utilising genetically isolated
      populations to reduce genetic and environmental noise and thus enhance
      association signals. In this study we performed heritability and blood-based eQTL
      association analysis of five key POAG endophenotypes in 330 individuals from the
      Norfolk Island (NI) isolate. Results showed evidence of heritability for all five
      traits, with H2 estimates ranging from 0.35 for intraocular pressure (IOP) to
      0.82 for central corneal thickness (CCT) (P < 0.05). The primary finding was for
      BTN3A2, whereby both cis-SNP and transcript were significantly associated with
      disc size within a conditional regression model. Specifically, this model
      included rs853676 (beta = 0.23,P = 0.008) and transcript (beta = 0.23, P = 0.03).
      We also observed a cis-SNP association between optic disc size and LPCAT2
      independent of transcript (P = 0.0004). These genes have specific functions in
      immune system pathways and suggest a role for an inherited immune component of
      POAG risk. This study also demonstrates an alternate approach to understanding
      the functional genetic basis of POAG and ocular health more generally.

PMID- 29215095
TI  - Homozygosity for a nonsense variant in AIMP2 is associated with a progressive
      neurodevelopmental disorder with microcephaly, seizures, and spastic
      quadriparesis.
AB  - We ascertained two unrelated consanguineous families with two affected children
      each having microcephaly, refractory seizures, intellectual disability, and
      spastic quadriparesis. Magnetic resonance imaging showed atrophy of cerebrum,
      cerebellum and spinal cord, prominent cisterna magna, symmetric T2 hypo
      intensities in the bilateral basal ganglia and thinning of corpus callosum. Whole
      exome sequencing of three affected individuals revealed c.105C>A [p.(Tyr35Ter)]
      variant in AIMP2. The variant lies in a common homozygous region of 940 kb on
      chromosome 7 and is likely to have been inherited from a common ancestor. The
      phenotype noted in our subjects' shares marked similarity with that of
      hypomyelinating leukodystrophy-3 caused by mutations in closely related gene
      AIMP1. We hereby report the first human disease associated with deleterious
      mutations in AIMP2.

PMID- 29215096
TI  - Exome sequencing revealed a novel nonsense variant in ALX3 gene underlying
      frontorhiny.
AB  - Frontorhiny is one of the two forms of mid-facial malformations characterized by
      ocular hypertelorism, wide and short nasal ridge, bifid nasal tip, broad
      columella, widely separated nares, long and wide philtrum and V-shaped hairline.
      Sometimes these phenotypes are associated with ptosis and midline dermoid cysts.
      Frontorhiny inherits in an autosomal recessive pattern. Sequence variants in the
      Aristaless-like homeobox 3 (ALX3) gene underlying frontorhiny have been reported
      previously. Here, in the present study, we have investigated four patients in a
      consanguineous family of Pakistani origin segregating frontorhiny in autosomal
      recessive manner. Genome scan using 250k Nsp1 array followed by exome and Sanger
      sequence analysis revealed a novel homozygous nonsense variant (c.604C>T,
      p.Gln202*) in the ALX3 gene resulting in frontorhiny in the family. This is the
      first mutation in the ALX3 gene, underlying frontorhiny, in Pakistani population.

PMID- 29215097
TI  - The molecular dialogue between Arabidopsis thaliana and the necrotrophic fungus
      Botrytis cinerea leads to major changes in host carbon metabolism.
AB  - Photoassimilates play crucial roles during plant-pathogen interactions, as
      colonizing pathogens rely on the supply of sugars from hosts. The competition for
      sugar acquisition at the plant-pathogen interface involves different strategies
      from both partners which are critical for the outcome of the interaction. Here,
      we dissect individual mechanisms of sugar uptake during the interaction of
      Arabidopsis thaliana with the necrotrophic fungus Botrytis cinerea using
      millicell culture insert, that enables molecular communication without physical
      contact. We demonstrate that B. cinerea is able to actively absorb glucose and
      fructose with equal capacities. Challenged Arabidopsis cells compete for
      extracellular monosaccharides through transcriptional reprogramming of host sugar
      transporter genes and activation of a complex sugar uptake system which displays
      differential specificity and affinity for hexoses. We provide evidence that the
      molecular dialogue between Arabidopsis cells and B. cinerea triggers major
      changes in host metabolism, including apoplastic sucrose degradation and
      consumption of carbohydrates and oxygen, suggesting an enhanced activity of the
      glycolysis and the cellular respiration. We conclude that beside a role in sugar
      deprivation of the pathogen by competing for sugar availability in the apoplast,
      the enhanced uptake of hexoses also contributes to sustain the increased activity
      of respiratory metabolism to fuel plant defences.

PMID- 29215099
TI  - Trigonal columnar self-assembly of bent phasmid mesogens.
AB  - Three compounds with a bent rod-like aromatic core and with three alkoxy chains
      at each end were synthesised by click reaction. The compounds form a columnar
      liquid crystal phase with non-centrosymmetric trigonal p31m symmetry, the columns
      having a 3-arm star-like cross-section.

PMID- 29215098
TI  - Proxies of quality of life in metastatic colorectal cancer: analyses in the
      RECOURSE trial.
AB  - Background: In the pivotal phase III, randomised, double-blind, placebo
      controlled RECOURSE study, treatment with trifluridine/tipiracil was well
      tolerated and associated with prolonged progression-free and overall survival in
      patients with metastatic colorectal cancer (mCRC). There was no formal analysis
      of quality of life (QoL) in RECOURSE. The aim of the present analysis was to
      assess proxies of QoL during the RECOURSE treatment period, in terms of adverse
      events (AEs) likely to affect QoL and Eastern Cooperative Oncology Group
      performance status (ECOG PS). Patients and methods: Enrolled patients had
      documented, previously treated (>=2 prior chemotherapy lines) mCRC and an ECOG PS
      of 0 or 1. Patients received best supportive care plus trifluridine/tipiracil 35
      mg/m2 twice daily (n=534) or placebo (n=266) in a 28-day cycle. AEs analysed
      included nausea, vomiting, diarrhoea, dysgeusia and fatigue/asthenia. ECOG PS was
      determined at baseline, on day 1 of each treatment cycle, at treatment end and 30
      days post-treatment discontinuation. Results: AEs that affect QoL were more
      frequent in patients treated with trifluridine/tipiracil than placebo. Median
      treatment duration for patients experiencing at least one of these AEs was longer
      than that observed for the overall RECOURSE population (trifluridine/tipiracil:
      12 vs 7 weeks; placebo: 10 vs 6 weeks). Versus placebo, the duration of most AEs
      was longer in trifluridine/tipiracil recipients; however, all AEs except nausea
      and vomiting occupied a lower proportion of the total treatment period. Of the
      patients who had their PS recorded at discontinuation, PS was maintained in 67%
      and 63% of trifluridine/tipiracil and placebo recipients, and 84% and 81% of the
      trifluridine/tipiracil and placebo patients remained at a PS of 0 or 1 at
      discontinuation. Conclusions: Analysis of ECOG PS and AEs thought to affect QoL
      in the RECOURSE patient population suggests that trifluridine/tipiracil treatment
      does not result in a deterioration of patient QoL versus placebo.

PMID- 29215100
TI  - Quillaja saponin-based hollow salt particles as solid carriers for enhancing
      sensory aroma with reduced sodium intake.
AB  - Dietary salt is a vital ingredient associated with sensory performance in
      processed foods, while reduced salt intake linked to public health is highly
      desired by consumers and food manufacturers. In this paper, quillaja saponin (QS)
      based hollow salt particles (~10 MUm) were fabricated by simple spray drying, and
      utilized as solid carriers to enhance sensory aromas with reduced sodium intake.
      QS-coated nanodroplets were firstly prepared as a reservoir for flavor oils
      (lemon and garlic oil), and then served as frameworks to construct hollow salt
      particles via general spray drying. Headspace gas chromatography-mass
      spectrometry (DHS-GC-MS) and panel sensory analysis conclude that the hollow salt
      particles loaded with flavor oils enhance typical aroma attributes and saltiness
      perception in comparison with their mixture control. The QS-based hollow salt
      particles could be developed into novel vehicles for improving flavor performance
      with reduced sodium intake, and furthermore used for delivery of hydrophobic
      bioactives in food systems.

PMID- 29215101
TI  - Evaluation of Cu(i) binding to the E2 domain of the amyloid precursor protein - a
      lesson in quantification of metal binding to proteins via ligand competition.
AB  - The extracellular domain E2 of the amyloid precursor protein (APP) features a His
      rich metal-binding site (denoted as the M1 site). In conjunction with surrounding
      basic residues, the site participates in interactions with components of the
      extracellular matrix including heparins, a class of negatively charged
      polysaccharide molecules of varying length. This work studied the chemistry of
      Cu(i) binding to APP E2 with the probe ligands Bcs, Bca, Fz and Fs. APP E2 forms
      a stable Cu(i)-mediated ternary complex with each of these anionic ligands. The
      complex with Bca was selected for isolation and characterization and was
      demonstrated, by native ESI-MS analysis, to have the stoichiometry E2 : Cu(i) :
      Bca = 1 : 1 : 1. Formation of these ternary complexes is specific for the APP E2
      domain and requires Cu(i) coordination to the M1 site. Mutation of the M1 site
      was consistent with the His ligands being part of the E2 ligand set. It is likely
      that interactions between the negatively charged probe ligands and a positively
      charged patch on the surface of APP E2 are one aspect of the generation of the
      stable ternary complexes. Their formation prevented meaningful quantification of
      the affinity of Cu(i) binding to the M1 site with these probe ligands. However,
      the ternary complexes are disrupted by heparin, allowing reliable determination
      of a picomolar Cu(i) affinity for the E2/heparin complex with the Fz or Bca probe
      ligands. This is the first documented example of the formation of stable ternary
      complexes between a Cu(i) binding protein and a probe ligand. The ready
      disruption of the complexes by heparin identified clear 'tell-tale' signs for
      diagnosis of ternary complex formation and allowed a systematic review of
      conditions and criteria for reliable determination of affinities for metal
      binding via ligand competition. This study also provides new insights into a
      potential correlation of APP functions regulated by copper binding and heparin
      interaction.

PMID- 29215102
TI  - Rational construction of a stable Zn4O-based MOF for highly efficient CO2 capture
      and conversion.
AB  - By employing a carboxylate ligand derived from benzene-1,4-dicarboxylate, a
      chemically stable Zn4O-based self-penetrating metal-organic framework has been
      rationally synthesized, which exhibits high CO2 adsorption and efficient
      catalytic conversion for CO2 cycloaddition.

PMID- 29215103
TI  - Soft X-ray activated NaYF4:Gd/Tb scintillating nanorods for in vivo dual-modal X
      ray/X-ray-induced optical bioimaging.
AB  - Lanthanide (Ln) nanocrystals using soft X-ray as an excitation source have
      received significant research interest due to the advantages of unlimited
      penetration depth of X-ray light. In this study, we demonstrated an efficient
      scintillator based on NaYF4:Gd nanorods (denoted as NRs) doped with different
      contents of terbium (Tb) ions for optical bioimaging under X-ray irradiation. The
      experimental results showed that the emission intensity was correlated to the
      doping contents of Tb3+, and the largest emission intensity was achieved by
      doping 15% Tb under excitation by soft X-ray light. In addition, the emission
      intensity of the as-prepared NRs can be significantly improved by increasing the
      excitation power and irradiation times of the X-ray. Owing to the efficient X-ray
      induced emission, these NRs were successfully used as probes for X-ray-induced
      optical bioimaging with high sensitivity. In addition, the dual-modal X-ray
      imaging and X-ray induced optical bioimaging were performed on a mouse, which
      indicated that the NRs were promising dual-modal bioprobes. Therefore, the X-ray
      activation nature of the designed NRs makes them promising probes for biomedicine
      and X-ray-induced photodynamic therapy (PDT) applications owing to the unlimited
      penetration depth of X-ray excitation source and absence of autofluorescence.

PMID- 29215104
TI  - A novel PTP1B inhibitor extracted from Ganoderma lucidum ameliorates insulin
      resistance by regulating IRS1-GLUT4 cascades in the insulin signaling pathway.
AB  - Insulin resistance caused by the overexpression of protein tyrosine phosphatase 1
      B (PTP1B) as well as the dephosphorylation of its target is one of the main
      causes of type 2 diabetes (T2D). A newly discovered proteoglycan, Fudan-Yueyang
      Ganoderma lucidum (FYGL) extracted from Ganoderma lucidum, was first reported to
      be capable of competitively inhibiting PTP1B activity in vitro in our previous
      work. In the present study, we sought to reveal the mechanism of PTP1B inhibition
      by FYGL at the animal and cellular levels. We found that FYGL can decrease blood
      glucose, reduce body weight and ameliorate insulin resistance in ob/ob mice.
      Decrease of PTP1B expression and increase of the phosphorylation of PTP1B targets
      in the insulin signaling pathway of skeletal muscles were observed. In order to
      clearly reveal the underlying mechanism of the hypoglycemic effect caused by
      FYGL, we further investigated the effects of FYGL on the PTP1B-involved insulin
      signaling pathway in rat myoblast L6 cells. We demonstrated that FYGL had
      excellent cell permeability by using a confocal laser scanning microscope and a
      flow cytometer. We found that FYGL had a positive effect on insulin-stimulated
      glucose uptake by using the 2-deoxyglucose (2-DG) method. FYGL could inhibit
      PTP1B expression at the mRNA level, phosphorylating insulin receptor substrate-1
      (IRS1), as well as activating phosphatidylinositol-3 kinase (PI3K) and protein
      kinase B (Akt). Finally, FYGL increased the phosphorylation of adenosine
      monophosphate-activated protein kinase (AMPK) and consequently up-regulated the
      expression of glucose transporter type 4 (GLUT4), promoting GLUT4 transportation
      to the plasma membrane in PTP1B-transfected L6 cells. Our study provides
      theoretical evidence for FYGL to be potentially used in T2D management.

PMID- 29215105
TI  - Synthesis and spectroscopic characterization of alkali-metal intercalated ZrSe2.
AB  - We report on the synthesis and spectroscopic characterization of alkali metal
      intercalated ZrSe2 single crystals. ZrSe2 is produced by chemical vapour
      transport and then Li is intercalated. Intercalation is performed from the liquid
      phase (via butyllithium) and from the vapour phase. Raman spectroscopy of
      intercalated ZrSe2 reveals phonon energy shifts of the Raman active A1g and Eg
      phonon modes, the disappearance of two-phonon modes and new low wavenumber Raman
      modes. Angle-resolved photoemission spectroscopy is used to perform a mapping of
      the Fermi surface revealing an electron concentration of 4.7 * 1014 cm-2. We also
      perform vapour phase intercalation of K and Cs into ZrSe2 and observe similar
      changes in the Raman modes as for the Li case.

PMID- 29215106
TI  - In situ synthesis of novel Cu2CO3(OH)2 decorated 2D TiO2 nanosheets with
      efficient photocatalytic H2 evolution activity.
AB  - Semiconductor-based photocatalytic hydrogen evolution from water with earth
      abundant and low cost co-catalysts has attracted much attention. Herein, novel
      Cu2(OH)2CO3 decorated 2D TiO2 nanosheets for photocatalytic water splitting were
      synthesized by a facile in situ synthetic method. The chemical and photophysical
      properties of Cu2(OH)2CO3/TiO2 nanosheets were investigated by X-ray
      diffractometry (XRD), transmission electron microscopy (TEM), UV-vis diffusion
      reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS) and cyclic
      voltammetry (CV) analysis. At an optimal Cu2(OH)2CO3 loading content of 1.5 mol%,
      the hybrid photocatalyst delivers a high photocatalytic H2 production rate of
      1555.07 MUmol g-1 h-1. Such enhanced photocatalytic activity is attributed to
      tight interfaces formed between Cu2(OH)2CO3 nanoparticles and TiO2 nanosheets,
      which play a vital role in the separation of photo-excited carriers, and the
      formation of active Cu1+ and Cu0 species can also benefit the charge separation
      process by reducing the over-potential of water reduction. Based on the above
      results, a possible mechanism is proposed and further verified using
      photoluminescence (PL) spectra. This work may provide more insight into the
      synthesis of novel Cu2(OH)2CO3/TiO2 nanosheets with high photocatalytic H2
      evolution activity for solar-to-chemical conversion and utilization.

PMID- 29215108
TI  - Carbodiimides as catalysts for the reduction of a cadmium hydride complex.
AB  - A rare terminal cadmium hydride complex [(BDI)CdH] (BDI = [{N(2,6
      iPr2C6H3)C(Me)}2CH]) has been synthesised from [(BDI)CdCl] and LiEt3BH. The
      hydride can be reduced to the cadmium(i) dimer, [(BDI)CdCd(BDI)] upon treatment
      with a catalytic amount of diisopropyl- or dicyclohexylcarbodiimide.

PMID- 29215107
TI  - beta-Carotene bioaccessibility from biofortified maize (Zea mays) is related to
      its density and is negatively influenced by lutein and zeaxanthin.
AB  - Biofortification of maize with provitamin A (pro-VA) carotenoids has been
      successful, but the bioavailability of carotenoids needs to be explored. In the
      present study, we investigated the carotenoid content, micellarization and
      intestinal cell uptake of carotenoids from 10 maize hybrids [normal maize,
      quality protein maize (QPM), pro-VA carotenoid and double biofortified QPM + pro
      VA maize hybrids] using a simulated in vitro digestion/Caco-2 cell model. The pro
      VA carotenoid content of biofortified maize hybrids is 2-10 fold higher compared
      to that of normal maize. Furthermore, the ratio of non-pro-VA carotenoids lutein
      (LUT) plus zeaxanthin (ZEA) to the sum of pro-VA carotenoids beta-cryptoxanthin
      (BCX), alpha-carotene (AC) and beta-carotene (BC) in biofortified maize was much
      lower compared to that of normal maize. The consumption of 200 g day-1 of
      biofortified Pusa-PV-16-3 (BC = 808.4 MUg per 100 g; AC = 839.3 MUg per 100 g;
      BCX = 59 MUg per 100 g) and Pusa-APQH8 (BC = 345.9 MUg per 100 g; AC = 1739 MUg
      per 100 g; BCX = 644.2 MUg per 100 g) maize would contribute to 52 and 64% of
      RDAs for adult Indian men, respectively, after adjusting for cooking losses and
      conversion factors. The mean efficiency of micellarization of LUT (62.2% +/-
      5.3), ZEA (65% +/- 4.7), and BCX (54% +/- 9.5) exceeded that of AC (43% +/- 8.9)
      and BC (49.8% +/- 7.8) from all the maize hybrids. Furthermore, the
      micellarization and uptake in Caco-2 cells during a 4 h incubation period showed
      high correlation (P < 0.05) with the concentration of carotenoids in the maize
      digesta and micellar fraction, respectively. However, the LUT + ZEA content in
      the maize digesta and micellar fraction was inversely (p < 0.05) related to the
      BC micellarization and intestinal cell uptake, respectively. These results
      together suggest that the enrichment of pro-VA carotenoids together with
      decreasing the oxygenated carotenoid metabolites such as LUT and ZEA will further
      improve the bioavailability of BC from maize hybrids.

PMID- 29215109
TI  - Giant negative magnetoresistance in Ni(quinoline-8-selenoate)2.
AB  - The magnetic, structural, conductivity and magnetoresistance properties of
      [Ni(quinoline-8-selenoate)2] ([Ni(qs)2]) have been studied. Despite the
      insolubility of the material necessitating its study as a powdered sample, a
      remarkably high conductivity has been measured. The conductivity is an order of
      magnitude greater than the thin-film processable thiol analogue previously
      reported and has been interpreted through the same space-charge limited
      conduction mechanism with charges injected from the electrodes. The introduction
      of selenium, results in a material with conductivity approaching metallic due to
      the enhanced interaction between adjacent molecules. Additionally, under an
      applied magnetic field, the material displays a negative magnetoresistance effect
      above 35% at 2 K. The effect can still be observed at 200 K and is interpreted in
      terms of a double-exchange mechanism.

PMID- 29215110
TI  - Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a
      polycystic kidney disease mouse model.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic
      disease characterized by massive enlargement of fluid-filled cysts in the kidney.
      There is an urgent need to develop effective ADPKD therapies. We used an in vitro
      Madin-Darby canine kidney (MDCK) cyst model and a murine embryonic kidney cyst
      model to evaluate whether quercetin inhibits cyst development. We then used a
      polycystic kidney disease (PKD) mouse model to further determine the in vivo
      effects of quercetin (100 mg per kg body weight twice per day) on PKD mice via
      subcutaneous injections. The results show that quercetin significantly and dose
      dependently inhibited cyst formation and enlargement in the MDCK cyst and
      embryonic kidney cyst models. Quercetin also noticeably reduced the cystic index
      in PKD mice. Furthermore, the effective dose of quercetin did not cause
      cytotoxicity in MDCK cells. Quercetin treatment decreased the levels of
      intracellular signalling proteins in PKD mouse kidneys, including phosphorylated
      protein kinase B (also known as AKT) and phosphorylated extracellular signal
      regulated kinase (ERK), which are upregulated and promote cyst development in
      ADPKD. Quercetin also reversed E-cadherin expression, which is localized in
      normal proximal tubules in PKD mouse kidneys. Taken together, these results
      demonstrate that quercetin hinders renal cyst development in vivo and in vitro
      and represents a novel candidate strategy for the treatment of ADPKD.

PMID- 29215111
TI  - Heteronuclear cobalt(iii)/sodium complexes with salen type compartmental Schiff
      base ligands: methylene spacer regulated variation in nuclearity.
AB  - Three heteronuclear cobalt(iii)/sodium Schiff base complexes have been
      synthesized and characterized by elemental and spectral analysis. The structures
      of all three complexes have been confirmed by single crystal X-ray analyses. Each
      of these three complexes crystallizes in monoclinic space group P21/c. In each
      complex, cobalt(iii) is placed in the inner N2O2 compartment and sodium is placed
      in the outer O2O'2 compartment (O and O' denote the phenolic and ethoxy/methoxy
      oxygen atoms, respectively) of the Schiff bases. With decrease in steric
      hindrance around the O2O'2 compartment by the replacement of ethyl groups with
      methyl groups, tetranuclear complexes resulted instead of dinuclear ones.
      Interesting carbon bonding interactions in the solid state of the complexes have
      been studied by means of DFT calculations using several computational tools such
      as "atoms-in-molecules" (AIM) and natural bond orbital (NBO) analyses.

PMID- 29215112
TI  - Ultrathin two-dimensional metals with fully exposed (111) facets.
AB  - Large-size ultrathin two-dimensional (2D) metals with a fully exposed (111)
      surface have been synthesized by a heat-pressing process. As a result of the
      compact (111) surface arrangement, an ultrathin Pt 5 nm 2D metal exhibits a
      superior methanol electro-oxidation performance than an as-sputtered Pt 5 nm thin
      film (1.8, 2.2 and 5.0 times higher specific activity under different scanning
      cycles).

PMID- 29215113
TI  - Li6Na3Sr14Al11P22O90: an oxo-centered Al3 cluster based phosphate constructed
      from two types of (3,6)-connected kgd layers.
AB  - A novel and thermally stable aluminum phosphate Li6Na3Sr14Al11P22O90 (1) has been
      achieved by using a solid-state molten method, which contains an oxo-centered
      trinuclear cluster and an anti-Lowenstein's rule Al-O-Al linkage and is
      constructed from two types of (3,6)-connected kgd layers [Al(Al3O)(PO4)7]25- and
      [Al(PO4)2]3-. The good optical transparency in the whole UV range and excellent
      thermal stability make the title compound a potential optical window material.

PMID- 29215114
TI  - Concentration-dependent binding of CdSe quantum dots on the SH3 domain.
AB  - Quantum dots (QDs) are being used increasingly in applications for solar panels,
      consumer electronics, and biomedical imaging. For biomedical applications, QDs
      are typically coated with a biocompatible molecule for the system of interest.
      Experiments have indicated a QD dose-dependent and surface coating-dependent
      toxicity, with a portion of the toxicity being ascribed to interference with
      biomolecules. In this work, the interaction of trioctylphosphine oxide (TOPO)
      coated (CdSe)13 QDs with the SRC homology 3 domain (SH3) protein domain are
      explored using molecular dynamics simulations. The results of this research agree
      well with experiments that show that at the lowest concentration, the QDs have
      little affinity for the native proline-rich motif (PRM) binding site of SH3. At
      higher concentrations, the QDs aggregate and increasingly prefer the PRM binding
      site, indicating that the normal SH3 function is impeded. This binding dependence
      is attributed to changes in the local density of the surface coated TOPO
      molecules upon aggregation. These results present possible interesting QD
      toxicity patterns and reveal the interdependence between dose and surface coating
      effects in QD toxicity.

PMID- 29215115
TI  - Perovskite photodetectors with both visible-infrared dual-mode response and super
      narrowband characteristics towards photo-communication encryption application.
AB  - Photo-communication has attracted great attention because of the rapid
      development of wireless information transmission technology. However, it is still
      a great challenge in cryptography communications, where it is greatly weakened by
      the openness of the light channels. Here, visible-infrared dual-mode narrowband
      perovskite photodetectors were fabricated and a new photo-communication
      encryption technique was proposed. For the first time, highly narrowband and two
      photon absorption (TPA) resultant photoresponses within a single photodetector
      are demonstrated. The full width at half maximum (FWHM) of the photoresponse is
      as narrow as 13.6 nm in the visible range, which is superior to state-of-the-art
      narrowband photodetectors. Furthermore, these two merits of narrowband and TPA
      characteristics are utilized to encrypt the photo-communication based on the
      above photodetectors. When sending information and noise signals with 532 and 442
      nm laser light simultaneously, the perovskite photodetectors only receive the
      main information, while the commercial Si photodetector responds to both lights,
      losing the main information completely. The final data are determined by the
      secret key through the TPA process as preset. Such narrowband and TPA detection
      abilities endow the perovskite photodetectors with great potential in future
      security communication and also provide new opportunities and platforms for
      encryption techniques.

PMID- 29215120
TI  - Searching for avidity by chemical ligation of combinatorially self-assembled DNA
      encoded ligand libraries.
AB  - DNA encoded ligands are self-assembled into bivalent complexes and chemically
      ligated to link their identities. To demonstrate their potential as a
      combinatorial screening platform for avidity interactions, the optimal bivalent
      aptamer design (examplar ligands) for human alpha-thrombin is determined in a
      single round of selection and the DNA scaffold replaced with minimal impact on
      the final design.

PMID- 29215121
TI  - Stabilizing benzene-like planar N6 rings to form a single atomic honeycomb BeN3
      sheet with high carrier mobility.
AB  - It is a longstanding quest to use the planar N6 ring as a structural unit to
      build stable atomic sheets. However, unlike C6H6, the neutral N6 ring is unstable
      due to the strong repulsion of the lone-pair of electrons. Using first-principles
      calculations and the global structure search method, we show that the N6 unit can
      be stabilized by the linkage of Be atoms, forming a h-BeN3 honeycomb monolayer,
      in which the geometry and the pi-molecular orbitals of the N6 rings are well
      kept. This sheet is not only energetically, dynamically and thermally stable, but
      also can withstand high temperatures up to 1000 K. Band structure calculation
      combined with a group theory analysis and a tight-binding model uncover that h
      BeN3 has a pi-band dominated band structure with an indirect band gap of 1.67 eV.
      While it possesses a direct band gap of 2.07 eV at the Gamma point lying in the
      photon energy region of visual light, its interband dipole transition is
      symmetrically allowed so that electrons can be excited by photons free of
      phonons. Based on deformation potential theory, a systematic study of the
      transport properties reveals that the h-BeN3 sheet possesses a high carrier
      mobility of ~103 cm2 V-1 s-1, superior to the extensively studied transition
      metal dichalcogenide monolayers. We further demonstrate that this sheet can be
      rolled up into either zigzag or armchair nanotubes. These nanotubes are also
      dynamically stable, and are all direct band gap semiconductors with carrier
      mobility comparable to that of their 2D counterparts, regardless of their
      chirality and diameter. The robust stability and novel electronic and transport
      properties of the h-BeN3 sheet and its tubular derivatives endow them with great
      potential for applications in nanoelectronic devices.

PMID- 29215122
TI  - Diarylmaleimide-based branched oligomers: strong full-color emission in both
      solution and solid films.
AB  - Maleimide and benzene are employed as a dendron and a core, respectively, to
      construct two series of non-conjugate branched oligomers (B3G1 and B1G2) based on
      diarylmaleimide fluorophores by an alkylation reaction. Surface aryl groups are
      changed to tune the emissive color of branched oligomers from blue (lambdaem =
      480 nm) to red (lambdaem = 651 nm), realizing full-color emission. The
      investigation on the photophysical properties of the oligomers indicates that
      they display intense emission in both solution and solid films, due to the
      suppression of intramolecular rotation and intermolecular interaction. Molecular
      simulation and natural transition orbital analysis show that the electron
      transition takes place in the individual arylmaleimide for the non-conjugate
      linkage of fluorophores in branched oligomers. It can avoid the unpredictability
      of the luminescence properties caused by the interaction of fluorophores. In
      addition, the good solubility, thermostability and oxidative stability of the
      branched oligomers make them have huge potential in the solution-processable
      photonic application. These results demonstrate that such a design strategy of
      non-conjugate branched oligomers is a very efficient and constructive method to
      obtain high-performance light-emitting materials in both solution and solid
      films.

PMID- 29215124
TI  - Shear thinning in non-Brownian suspensions.
AB  - We study the flow of suspensions of non-Brownian particles dispersed into a
      Newtonian solvent. Combining capillary rheometry and conventional rheometry, we
      evidence a succession of two shear thinning regimes separated by a shear
      thickening one. Through X-ray radiography measurements, we show that during each
      of those regimes, the flow remains homogeneous and does not involve particle
      migration. Using a quartz-tuning fork based atomic force microscope, we measure
      the repulsive force profile and the microscopic friction coefficient MU between
      two particles immersed into the solvent, as a function of normal load. Coupling
      measurements from those three techniques, we propose that (1) the first shear
      thinning regime at low shear rates occurs for a lubricated rheology and can be
      interpreted as a decrease of the effective volume fraction under increasing
      particle pressures, due to short-ranged repulsive forces and (2) the second shear
      thinning regime after the shear-thickening transition occurs for a frictional
      rheology and can be interpreted as stemming from a decrease of the microscopic
      friction coefficient at large normal load.

PMID- 29215125
TI  - Large scale 2D/3D hybrids based on gallium nitride and transition metal
      dichalcogenides.
AB  - Two and three-dimensional (2D/3D) hybrid materials have the potential to advance
      communication and sensing technologies by enabling new or improved device
      functionality. To date, most 2D/3D hybrid devices utilize mechanical exfoliation
      or post-synthesis transfer, which can be fundamentally different from directly
      synthesized layers that are compatible with large scale industrial needs.
      Therefore, understanding the process/property relationship of synthetic
      heterostructures is priority for industrially relevant material architectures.
      Here we demonstrate the scalable synthesis of molybdenum disulfide (MoS2) and
      tungsten diselenide (WSe2) via metal organic chemical vapor deposition (MOCVD) on
      gallium nitride (GaN), and elucidate the structure, chemistry, and vertical
      transport properties of the 2D/3D hybrid. We find that the 2D layer thickness and
      transition metal dichalcogenide (TMD) choice plays an important role in the
      transport properties of the hybrid structure, where monolayer TMDs exhibit direct
      tunneling through the layer, while transport in few layer TMDs on GaN is
      dominated by p-n diode behavior and varies with the 2D/3D hybrid structure.
      Kelvin probe force microscopy (KPFM), low energy electron microscopy (LEEM) and X
      ray photoelectron spectroscopy (XPS) reveal a strong intrinsic dipole and charge
      transfer between n-MoS2 and p-GaN, leading to a degraded interface and high p
      type leakage current. Finally, we demonstrate integration of heterogeneous 2D
      layer stacks of MoS2/WSe2 on GaN with atomically sharp interface. Monolayer
      MoS2/WSe2/n-GaN stacks lead to near Ohmic transport due to the tunneling and non
      degenerated doping, while few layer stacking is Schottky barrier dominated.

PMID- 29215126
TI  - Can the Local Health Unit staff serve as role model for positive health
      behaviours? Results from an observational study in Italy.
AB  - BACKGROUND: Lifestyles as well as health behaviors and attitudes are a matter of
      personal health and a public health concern for healthcare providers. The aims of
      the study were to examine lifestyles and health behaviors - i.e., smoking habit,
      diet, predisposition to undergo for cancer screening tests among the staff of a
      Local Health Unit in Rome and the prevalence of some of the major preventable
      chronic degenerative pathologies associated to lifestyles. METHODS: The survey
      was carried out through the administration of a questionnaire. Descriptive and
      univariate analyses were performed and binary logistic regression models were
      used to identify possible associations with an unhealthy lifestyles. Hosmer
      Lemeshow test was performed. The level of significance was set at p <= 0.05.
      RESULTS: 355 employees entered the study (87,8%); 43.4% resulted in
      overweight/obesity and 36.6% is a current smoker. Those with a high degree of
      studies had an higher odds to be smokers (for low education OR=0.76; 95% CI:0,61
      0.94) and healthcare workers were less likely to follow an unhealthy diet than
      administrative staff (OR=0.52; 95% CI: 0.29-0.91). CONCLUSION: Despite the Local
      Health Unit employees have, in the specific context of their workplace, an
      important role in promoting healthy lifestyles, in our survey they show unhealthy
      habits and lifestyles.

PMID- 29215128
TI  - Developing a subset of ICNP nursing diagnoses for medical and surgical hospital
      settings, informed by an Italian nursing conceptual model: a multicenter cross
      sectional study.
AB  - BACKGROUND: The International Classification for Nursing Practice (ICNP) is
      designed to facilitate the expression of nursing diagnoses, interventions and
      outcomes. The development of the ICNP subsets may support nurses by providing
      appropriate terms for documenting nursing care. This project aimed to develop a
      subset of ICNP nursing diagnoses oriented by an Italian Nursing Conceptual Model
      (MPI) to describe nursing clinical data in medical and surgical acute hospital
      wards. STUDY DESIGN: A subset of ICNP nursing diagnoses was developed based on a
      literature review and on an expert consensus. A cross-sectional study was
      conducted in three Northern Italian hospitals to empirically test the subset in
      target settings. METHODS: In accordance with the guidelines adopted by the
      International Council of Nursing, the study followed the process for developing
      an ICNP subset. Twelve expert nurses from clinical settings and nursing education
      in surgical and medical care participated in a Delphi method to further validate
      the subset. A cross-mapping process has been implemented and the prevalence of
      diagnoses was described. Data were collected from healthcare documentation of
      admitted patients, including, retrospectively, nursing clinical data from the
      patients' admission date to the time of data collection. RESULTS: Documentation
      from 476 admitted patients was analysed: 228 were from surgical and 248 from
      medical wards. 24,142 nursing diagnoses were detected consulting retrospectively
      each documentation. A total number of 21,401 nursing diagnoses (88%) were fully
      mapped by the ICNP subset. CONCLUSION: Results showed a high capability of ICNP
      terminology to describe nursing care in acute medical and surgical areas in
      Italian hospitals. The identified subset of ICNP diagnoses could be a valuable
      way to support a computerized documentation system for hospitals using MPI and
      ICNP. Results could be used to start revising nursing education programs in order
      to introduce this nursing standardized terminology combining it with the nursing
      conceptual model in use.

PMID- 29215127
TI  - Midwives in England and in Italy: two realities compared.
AB  - BACKGROUND: Midwives have the responsibility to provide assistance to pregnant
      women for non-complicated deliveries. The aim of this study was to identify the
      distinctive features of midwives in Italy and in England in order to provide
      interesting comparisons. METHODS: From September to October 2015 we administered
      an online questionnaire to groups of Italian and English midwives. The
      questionnaire was composed by a part trying to collect the sociodemographic
      information and a second part to define the attitudes of care and the type of
      approach to birth and degree of attained professional autonomy. The questions
      were used to create a score for 5 macro areas: "Midwifery: who is the midwife?",
      "Education: how much does the midwife know?", "Responsibility: what does the
      midwife do?", "Ethics: how does the midwife act?", "Social acknowledgment: the
      midwife and the other people". Results were loaded in a database and analyzed
      using the using STATA. RESULTS: 183 Midwives (100 Italian and 83 English)
      completed the questionnaire. 92% of Italian respondents said to have a
      "Bachelor", 6% a "University Diploma" and only 2% a "Diploma". 80% of British
      midwives had a "Midwifery Degree" and 8% attended a "Midwifery Short Program", a
      degree course in Nursing with an additional specialization of a year and a half
      in Midwifery. 34% of the Italian claimed to have also a "1st level Master", 16% a
      "Full Degree" and the remaining 50% attended post degree training courses. Only
      23% of the English sample had a "Master of Science" and the remaining 67%
      reported to have "other" general qualifications. 72% of Italian midwives declared
      to work and, in particular, in a "III level point of birth" (35%), "II level
      point of birth" (25%), "I level point of birth" (17%), or in "private health
      facilities" (4%), in "professional offices" (6%) or "counseling ambulatories"
      (5%). 46% of the English midwives who participated in the study worked in
      hospitals; 21% as employees of the NHS in territorial structures. 12% worked in
      birth centers and 11% had a private profession. There was a statistically
      significant difference between Italian and English Midwives, for all the macro
      areas (except for the first), with better results for English Midwives.
      CONCLUSION: English Midwives tend to consider their professional role and their
      professional skills more acknowledged and appreciated than Italian Midwives.
      Actually Italians tend to be not very satisfied. However, the Midwives of both
      countries feel very close to women and have the same conception of themselves and
      of their profession.

PMID- 29215129
TI  - The aquifer recharge: an overview of the legislative and planning aspect.
AB  - In most regions of the world, safeguarding groundwater resources is a serious
      issue, particularly in coastal areas where groundwater is the main water source
      for drinking, irrigation and industry. Water availability depends on climate,
      topography and geology. The aim of this paper is to evaluate aquifer recharge as
      a possible strategy to relieve water resource scarcity. Natural aquifer recharge
      is defined as the downward flow of water reaching the water table, increasing the
      groundwater reservoir. Hydro-meteorological factors (rainfall, evapotranspiration
      and runoff) may alter natural recharge processes. Artificial aquifer recharge is
      a process by which surface water is introduced with artificial systems
      underground to fill an aquifer. As a consequence of global warming that has
      increased the frequency and severity of natural disasters like the drought, the
      impacts of climate change and seasonality, the artificial recharge has been
      considered as a viable option. Different direct and indirect techniques can be
      used, and the choice depends on the hydrologic characteristics of a specific
      area. In Italy, Legislative Decree no. 152/06 plans artificial aquifer recharge
      as an additional measure in water management, and Decree no. 100/2016 establishes
      quantitative and qualitative conditions for recharge. Many projects examine
      aquifer recharge, such us WADIS-MAR in the southern Mediterranean region, WARBO
      in Italy and municipal wastewater treatment project in Apulia, a southern Italian
      region. However, aside from groundwater recharge, the community must foster a
      spirit of cooperation to manage groundwater as a sustainable resource.

PMID- 29215130
TI  - Use of anticoagulant rodenticides in outdoor urban areas: considerations and
      proposals for the protection of public health and non-target species.
AB  - Rodent control operations represent an important tool for the prevention and
      management of infestations, in outdoor environments, by synanthropic rodents
      (Rattus rattus and R. norvegicus), which are a source of economic and
      environmental damage with significant sanitary implications. Although the use of
      anticoagulants is safer to humans and pets compared to the use of acute poisoning
      substances, an intrinsic hazard of the active ingredients exists, i.e. the
      possible poisoning of non-target organisms (e.g., children, pets and wildlife)
      following exposure. The risks arising from the use of anticoagulants for rodent
      control operations in anthropic contexts can therefore only be mitigated by a
      proper selection of the active ingredient, bait formulation and administration
      techniques, since an active ingredient with selective action towards non-target
      species does not currently exist on the market. This document lists practical
      proposals aimed at reducing the possibility of toxic exposure to anticoagulant
      rodenticides and mitigate the toxicological risk of human baits and non-target
      species.

PMID- 29215131
TI  - Prevalence of overweight and obesity in an Italian Prison and relation with
      average term of detention: a pilot study.
AB  - INTRODUCTION: Obesity and overweight are universally recognized as risk factors
      for cardiovascular disease, stroke and other chronic diseases. The few studies of
      overweight and obesity in inmate populations suggest that the prevalence of
      obesity in an institution is associated with the prevalence of the region. The
      goal of the study is to describe the prevalence of overweight and obesity in a
      sample of prisoners. METHODS: In a sample of prisoners of Busto Arsizio prison,
      weight and height were measured with standard method., Once collected information
      about nationality, age and duration of detention, we proceeded to calculate BMI
      and the prevalence of overweight and obesity. RESULTS: The subjects enrolled were
      142, all males, aged 19-66 years, with a holding period of between 30 days and
      two years. From the survey, the total of obese or overweight subjects was 66.9%.
      In the comparison between Italian and Foreign prisoners, the latter showed the
      highest weight gain. The analysis of the correlation between increased BMI and
      length of detention has not shown a statistical association during detention, but
      it could depend on the number of inmates enrolled. CONCLUSION: The prevalence of
      obesity and overweight among inmates (66.9%) was higher than the Italian general
      population (54.8%, adult males, ISTAT, 2015). The decreasing physical activity
      typical of the detention, the psycho-physical discomfort (incarceration trauma)
      and the prison meals could have had a significant importance in increasing
      weight. Desirable therefore more investigations (calculation of caloric needs,
      ethnic and religious diets, eating disorders) in order to establish appropriate
      preventive interventions.

PMID- 29215132
TI  - May car washing represent a risk for Legionella infection?
AB  - BACKGROUND: Legionella is a ubiquitous Gram-negative bacterium naturally found in
      aquatic environments. It can pose a health problem when it grows and spreads in
      man-made water systems. Legionella pneumophila is the most common cause of
      Legionnaires' disease nowadays, a community-acquired pneumonia with pulmonary
      symptoms and chest radiography no different from any other form of infectious
      pneumonia. Legionella monitoring is important for public health reasons,
      including the identification of unusual environmental sources of Legionella.
      METHODS: We report two cases of Legionnaires' disease associated with two
      different car wash installations in the province of Vicenza, in the Veneto
      region, northeastern Italy. Patients were not employees of the car wash
      installations, but users of the service. In both cases, Legionella antigen was
      detected in urine using the Alere BinaxNOW(r) Legionella Urinary Antigen, and
      Legionella antibodies were detected in serum using SERION ELISA classic
      Legionella pneumophila 1-7 IgG and IgM. Water samples were also analyzed as part
      of the surveillance program for Legionella prevention and control in compliance
      with the Italian guidelines. RESULTS: Both patients had clinical symptoms and
      chest radiography compatible with pneumonia, and only one of them had diabetes as
      a risk factor. Legionella urinary antigen and serological test on serum samples
      were positive for Legionella in both patients, even if much slighter in the case
      A due to the retrospective serological investigation performed a year later the
      episode and after the second clinical case occurred in the same district. The
      environmental investigations highlighted two different car wash plants as
      potential source of infection. A certified company using shock hyperchlorination
      was asked to disinfect the two plants and, subsequently, control samples resulted
      negative for Legionella pneumophila. CONCLUSION: Any water source producing
      aerosols should be considered at risk for the transmission of Legionella
      bacteria, including car wash installations frequently used by a large number of
      customers and where poor maintenance probably creates favorable conditions for
      Legionella overgrowth and spreading. Additional research is needed to ascertain
      optimal strategies for Legionella monitoring and control, but environmental
      surveillance, paying careful attention to possible unconventional sources, should
      remain an important component of any Legionnaires' disease prevention program.
      Additionally, all available diagnostic methods would be recommended for the
      confirmation of all cases even in the event of non-serogroup 1 Legionella
      pneumophila infection, probably underestimated at this time.

PMID- 29215133
TI  - A five year retrospective study on Syphilis in the Sexual Transmitted Disease
      Centre (STDC) of the teaching Hospital Umberto I in Rome.
AB  - OBJECTIVES: A retrospective study describing syphilis epidemiological and
      clinical features in patients referring to an infectious diseases centre in Rome,
      Italy. METHODS: Between January 2011 and December 2015 demographic, behavioral
      and clinical data were collected from all adult patients attending the Sexually
      Transmitted Diseases Centre of the Teaching Hospital Umberto I in Rome. RESULTS:
      Overall 723 patients, 495 males and 228 females, with syphilis infection
      diagnosis were included. Average age 39.6 +/- 13.6 years (median 38) was higher
      in men than women (41.1 +/- 13.6 vs. 36.3 +/- 13.1; p<0.001). Patients were from
      Italy (486 or 67.2%), EU (90 or 12.4%), rest of Europe (38 or 5.3 %), Americas
      (46 or 6.4%), Africa (36 or 5.0%) and Asia (27 or 3.7%). One-hundred-twenty-three
      (17.0%) presented primary syphilis, 43 (5.9%) secondary syphilis, 8 (1.1%)
      tertiary syphilis, 246 (34.0%) serological syphilis, 80 (11.1%) preceding
      syphilis, 56 (7.7%) gravidic syphilis and 167 (23.1%) came to the Sexually
      Transmitted Diseases Centre to control a preceding syphilis treatment. Fifty-six
      (24.6%) women were diagnosed with syphilis during their pregnancies. Among
      Chinese female patients, those pregnant represented 87.5%. There were 100
      subjects (13.8%) simultaneously HIV+ and 623 (86.2%) HIV- patients. HIV co
      infection affected more frequently men (RR 5.30; CI 2.62 - 10.72; p<0.001). In
      males HIV co-infection affected more frequently homosexuals (RR 11.72; CI 6.72 -
      20.45; p<0.001). Overall HIV co-infection affected more frequently foreign
      patients, specially from the Americas (26.1%), Africa (25.7%) and Asia (22.2%).
      CONCLUSION: A serious problem of "gravidic syphilis" suggests the need for Public
      Health preventive action. Also an early diagnosis of both syphilis and HIV
      infection should be reinforced.

PMID- 29215134
TI  - Malaria chemoprophylaxis' compliance in travelers.

PMID- 29215135
TI  - "Five-A-Day" and the Med-Food Anticancer Program.

PMID- 29215136
TI  - Spontaneous intracerebral hemorrhage as presentation of atypical central
      neurocytoma: the role of angiogenesis through the characterization of tumor
      endothelial cells.
AB  - A 36-year-old white man presented with sudden-onset headache and rapid
      deterioration of consciousness. Computer tomography revealed a right capsular
      intra-parenchimal hemorrhage with an intraventricular component; therefore,
      emergency surgery was performed. Once the hematoma was evacuated, the cause of
      the hemorrhage was identified as a tumor mass and it was resected.
      Histopathological and immunohistochemical examinations of the surgical specimen
      disclosed a diagnosis of atypical central neurocytoma. By using a protocol
      recently set up in our laboratory, we succeeded in isolating and propagating, for
      the first time, human endothelial cells from central neurocytoma (CN-ECs).
      Different analyses revealed that isolated CN-ECs consist of a pure endothelial
      cell population, with the expression of endothelial markers (CD31, CD309/VEGFR2,
      CD105, eNOS) and with angiogenic properties, such as the uptake of LDL. Moreover,
      CN-ECs spontaneously organize in a vascular-like structure. The goal of this case
      report is to stress the need for further studies focused on understanding the
      causes of the onset of an intra-parenchimal hemorrhage in the presence of an
      atypical central neurocytoma in order to tailor treatments to each single patient
      and achieve the best clinical outcome.

PMID- 29215137
TI  - Frequency and phase correction for multiplexed edited MRS of GABA and
      glutathione.
AB  - PURPOSE: Detection of endogenous metabolites using multiplexed editing
      substantially improves the efficiency of edited magnetic resonance spectroscopy.
      Multiplexed editing (i.e., performing more than one edited experiment in a single
      acquisition) requires a tailored, robust approach for correction of frequency and
      phase offsets. Here, a novel method for frequency and phase correction (FPC)
      based on spectral registration is presented and compared against previously
      presented approaches. METHODS: One simulated dataset and 40 gamma-aminobutyric
      acid-/glutathione-edited HERMES datasets acquired in vivo at three imaging
      centers were used to test four FPC approaches: no correction; spectral
      registration; spectral registration with post hoc choline-creatine alignment; and
      multistep FPC. The performance of each routine for the simulated dataset was
      assessed by comparing the estimated frequency/phase offsets against the known
      values, whereas the performance for the in vivo data was assessed quantitatively
      by calculation of an alignment quality metric based on choline subtraction
      artifacts. RESULTS: The multistep FPC approach returned corrections that were
      closest to the true values for the simulated dataset. Alignment quality scores
      were on average worst for no correction, and best for multistep FPC in both the
      gamma-aminobutyric acid- and glutathione-edited spectra in the in vivo data.
      CONCLUSIONS: Multistep FPC results in improved correction of frequency/phase
      errors in multiplexed gamma-aminobutyric acid-/glutathione-edited magnetic
      resonance spectroscopy experiments. The optimal FPC strategy is experiment
      specific, and may even be dataset-specific. Magn Reson Med 80:21-28, 2018. (c)
      2017 International Society for Magnetic Resonance in Medicine.

PMID- 29215138
TI  - Premenstrual syndrome and premenstrual dysphoric disorders among Jordanian women.
AB  - PURPOSE: The aim of this study was to investigate the frequency, associated
      factors, and management approaches of premenstrual dysphoric disorder (PMDD) and
      premenstrual syndrome (PMS) in Jordanian women. DESIGN AND METHODS: Three hundred
      premenopausal women completed a self-administered questionnaire. FINDINGS:
      Moderate-severe PMS was reported by 29% of women, while 14% had PMDD. Younger
      unmarried women had the more severe condition. Herbal remedies and no medication
      were the most common approaches used to manage PMS/PMDD. IMPLICATIONS FOR NURSING
      PRACTICE: High rates of PMS and PMDD found in this study highlight the need to
      increase awareness to this condition among health providers in order to
      facilitate its identification, diagnosis, and management.

PMID- 29215139
TI  - A Novel and Selective Nociceptin Receptor (NOP) Agonist (1-(1-((cis)-4
      isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol (AT-312) Decreases
      Acquisition of Ethanol-Induced Conditioned Place Preference in Mice.
AB  - BACKGROUND: Nociceptin/orphanin FQ, the endogenous peptide agonist for the opioid
      receptor-like receptor (also known as NOP or the nociceptin receptor), has been
      shown to block the acquisition and expression of ethanol (EtOH)-induced
      conditioned place preference (CPP). Here, we report the characterization of a
      novel small-molecule NOP ligand AT-312 (1-(1-((cis)-4
      isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol) in receptor binding
      and GTPgammaS functional assays in vitro. We then investigated the effect of AT
      312 on the rewarding action of EtOH in mice using the CPP paradigm. Further,
      using mice lacking the NOP receptor and their wild-type controls, we also
      examined the involvement of NOP in the effect of AT-312. Motivational effects of
      AT-312 alone were also assessed in the CPP paradigm. METHODS: Female mice lacking
      NOP and/or their wild-type controls received conditioning in the presence or
      absence of the NOP agonist [AT-312 (1, 3, and 10 mg/kg) or the control NOP
      agonist SCH221510 (10 mg/kg)] followed by saline/EtOH for 3 consecutive days
      (twice daily) and tested for CPP in a drug-free state on the next day. RESULTS:
      Our in vitro data showed that AT-312 is a high-affinity, selective NOP full
      agonist with 17-fold selectivity over the mu opioid receptor and >200-fold
      selectivity over the kappa opioid receptor. The results of our in vivo studies
      showed that AT-312 reduced EtOH CPP at the lowest dose (1 mg/kg) tested but
      completely abolished EtOH CPP at higher doses (3 or 10 mg/kg) compared to their
      vehicle-treated control group. AT-312 (3 mg/kg) did not alter EtOH-induced CPP in
      mice lacking NOP, confirming that AT-312 reduced EtOH CPP through its action at
      the NOP receptor. AT-312 (3 mg/kg) did not induce reward or aversion when
      administered alone, showing that the novel small-molecule NOP agonist shows
      efficacy in blocking EtOH-induced CPP via the NOP receptor. CONCLUSIONS:
      Together, these data suggest that small-molecule NOP agonists have the potential
      to reduce alcohol reward and may be promising as medications to treat alcohol
      addiction.

PMID- 29215140
TI  - Change of the structure and the digestibility of myofibrillar proteins in Nanjing
      dry-cured duck during processing.
AB  - BACKGROUND: To investigate the change of bioavailability and structure of
      myofibrillar proteins during Nanjing dry-cured duck processing, carbonyl content,
      sulfhydryl (SH) group, disulfide (S?S) group, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, surface hydrophobicity, secondary structures
      and in vitro digestibility were determined. RESULTS: During processing, carbonyl
      content and surface hydrophobicity increased; SH turned into S?S group; alpha
      helix turned into beta-sheet and random coil fractions. Protein degradation
      occurred during dry-curing and drying-ripening stages. The in vitro digestibility
      of pepsin and pancreatic proteases increased during the salt curing stage and
      decreased during the drying-ripening stage. CONCLUSION: The increase of
      digestibility could be attributed to the mild oxidation, degradation and
      unfolding of proteins while the decrease of digestibility was related to the
      intensive oxidation and aggregation of proteins. Protein degradation was not a
      main factor of digestibility during the drying-ripening stage. Results
      demonstrated that the bioavailability loss of myofibrillar proteins in Nanjing
      dry-cured duck occurred during the stage of drying-ripening instead of curing.
      (c) 2017 Society of Chemical Industry.

PMID- 29215141
TI  - Highly Efficient Gating of Electrically Actuated Nanochannels for Pulsatile Drug
      Delivery Stemming from a Reversible Wettability Switch.
AB  - Many ion channels in the cell membrane are believed to function as gates that
      control the water and ion flow through the transitions between an inherent
      hydrophobic state and a stimuli-induced hydration state. The construction of
      nanofluidic gating systems with high gating efficiency and reversibility is
      inspired by this hydrophobic gating behavior. A kind of electrically actuated
      nanochannel is developed by integrating a polypyrrole (PPy) micro/nanoporous film
      doped with perfluorooctanesulfonate ions onto an anodic aluminum oxide nanoporous
      membrane. Stemming from the reversible wettability switch of the doped PPy film
      in response to the applied redox potentials, the nanochannels exhibit highly
      efficient and reversible gating behaviors. The optimized gating ratio is over 105
      , which is an ultrahigh value when compared with that of the existing reversibly
      gated nanochannels with comparable pore diameters. Furthermore, the gating
      behavior of the electrically actuated nanochannels shows excellent repeatability
      and stability. Based on this highly efficient and reversible gating function, the
      electrically actuated nanochannels are further applied for drug delivery, which
      achieves the pulsatile release of two water-soluble drug models. The electrically
      actuated nanochannels may find potential applications in accurate and on-demand
      drug therapy.

PMID- 29215142
TI  - Cortical thickness, resting state heart rate, and heart rate variability in
      female adolescents.
AB  - Resting state heart rate variability (HRV) is a psychophysiological marker that
      has gained increasing research interest, in particular in developmental
      neuroscience. HRV has been shown to be associated with mental and physical
      health, beyond simple measures of heart rate (HR) and shows inter- and
      intraindividual variance across aging. Recently, three studies reported on a
      positive correlation between resting state HRV and cortical thickness in selected
      regions of interest (ROIs) in adult samples. Structural thickness, HRV, and HR
      change during the sensitive period of adolescence. Previously, no study has
      addressed the structural concomitants of resting HR and HRV in adolescents.
      Cortical thickness (3-T MRI), HR, and HRV were recorded in 20 healthy, female
      adolescents (mean age: 15.92 years; SD = 1.06; range: 14-17). In line with
      existing research in adults, cortical thickness in a number of ROIs was
      associated with resting state HRV but not HR. The comparison of regression
      analyses using the Bayes factor revealed evidence for a correlation between HRV
      and cortical thickness of the bilateral rostral anterior cingulate cortex.
      However, unlike in adults, greater cortical thickness was associated with reduced
      HRV in female adolescents. Analyses on HR showed no superior model fit. Results
      suggest that greater HRV might be beneficial for cortical development during
      adolescence (cortical thinning). On the other hand, cortical development might
      determine changes in autonomic nervous system function in adolescents. Future
      studies are needed to replicate these findings in larger samples including boys
      and to test these hypotheses in longitudinal designs.

PMID- 29215143
TI  - Generalized pustular psoriasis in a 92-year-old man with a homozygous nonsense
      mutation in IL36RN.
AB  - A 92-year-old man developed an erythematous eruption on the trunk and extremities
      with numerous pustules accompanied by fever. He had never experienced pustular
      eruption or been diagnosed with psoriasis previously. Skin biopsy revealed
      Kogoj's spongiform pustule, and he was diagnosed with generalized pustular
      psoriasis (GPP). Genomic DNA was extracted from his peripheral blood and the
      sequence of IL36RN gene was analyzed, which revealed a p.Arg10X homozygous
      mutation. Several cases of elderly-onset GPP have been reported, however, this is
      the oldest case of GPP. The existence of splice variants of IL36RN was suspected,
      but we could not detect any splice variants of IL36RN in this case or in a
      healthy control from peripheral blood samples.

PMID- 29215144
TI  - Physiological coherence in healthy volunteers during laboratory-induced stress
      and controlled breathing.
AB  - Physiological coherence has been related with a general sense of well-being and
      improvements in health and physical, social, and cognitive performance. The aim
      of this study was to evaluate the relationship between acute stress, controlled
      breathing, and physiological coherence, and the degree of body systems
      synchronization during a coherence-generation exercise. Thirty-four university
      employees were evaluated during a 20-min test consisting of four stages of 5-min
      duration each, during which basal measurements were obtained (Stage 1), acute
      stress was induced using validated mental stressors (Stroop test and mental
      arithmetic task, during Stage 2 and 3, respectively), and coherence states were
      generated using a controlled breathing technique (Stage 4). Physiological
      coherence and cardiorespiratory synchronization were assessed during each stage
      from heart rate variability, pulse transit time, and respiration. Coherence
      measurements derived from the three analyzed variables increased during
      controlled respiration. Moreover, signals synchronized during the controlled
      breathing stage, implying a cardiorespiratory synchronization was achieved by
      most participants. Hence, physiological coherence and cardiopulmonary
      synchronization, which could lead to improvements in health and better life
      quality, can be achieved using slow, controlled breathing exercises. Meanwhile,
      coherence measured during basal state and stressful situations did not show
      relevant differences using heart rate variability and pulse transit time. More
      studies are needed to evaluate the ability of coherence ratio to reflect acute
      stress.

PMID- 29215145
TI  - Successful treatment of iatrogenic Kaposi's sarcoma with low-dose docetaxel
      therapy.

PMID- 29215146
TI  - Case of thymoma-associated cutaneous graft-versus-host disease-like disease
      successfully improved by narrowband ultraviolet B phototherapy.
AB  - Thymoma-associated graft-versus-host disease (GVHD)-like disease is a rare
      paraneoplastic disease seen in patients with thymoma. Here, we describe the first
      case of thymoma-associated GVHD-like disease localized to the skin that was
      successfully improved by a combination of systemic corticosteroids and whole-body
      narrowband ultraviolet (UV)-B phototherapy. The patient had developed toxic
      epidermal necrolysis-like erosive skin lesions over the whole body. Although
      systemic corticosteroids were effective up to a point, we were unable to begin
      the steroid taper. The addition of systemic narrowband UV-B phototherapy improved
      the skin manifestation of this disease, allowing corticosteroids to be reduced to
      a third of the original dose. Histopathologically, it was confirmed that the
      proportion of Foxp3-positive lymphocytes in the skin increased after narrowband
      UV-B irradiation. We propose that whole-body narrowband UV-B phototherapy is a
      good therapeutic option for the skin manifestation of thymoma-associated GVHD
      like disease.

PMID- 29215147
TI  - Case of generalized morphea with the manifestation of diffuse systemic cutaneous
      sclerosis without sclerodactyly.

PMID- 29215148
TI  - 31 P T2 s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the
      human brain at 7T.
AB  - PURPOSE: To determine the phosphorus-31 T2 s of phosphomonoesters,
      phosphodiesters, and inorganic phosphate in the healthy human brain at 7T.
      METHODS: A 3D chemical shift imaging multi-echo sequence with composite block
      pulses for refocusing was used to measure one free induction decay (FID) and
      seven full echoes with an echo spacing of 45 ms on the brain of nine healthy
      volunteers (age range 22-45 years; average age 27 +/- 8 years). Spectral fitting
      was used to determine the change in metabolic signal amplitude with echo time.
      RESULTS: The average apparent T2 s with their standard deviation were 202 +/- 6
      ms, 129 +/- 6 ms, 86 +/- 2 ms, 214 +/- 10 ms, and 213 +/- 11 ms for
      phosphoethanolamine, phosphocholine, inorganic phosphate,
      glycerophosphoethanolamine, and glycerophosphocholine, respectively. CONCLUSION:
      The determined apparent T2 for phosphoethanolamine, glycerophosphocholine, and
      glycerophosphoethanolamine is approximately 200 ms. The lower apparent T2 value
      for phosphocholine is attributed to the overlap of this resonance with the 3
      phosphorous resonance of 2,3-diphosphoglycerate from blood, with an apparent
      shorter T2 . Omitting the FID signal and the first echo of phosphocholine leads
      to a T2 of 182 +/- 7 ms, whereas a biexponential analysis leads to 203 +/- 4 ms.
      These values are more in line with phosphoethanolamine and the phosphodiesters.
      The short T2 of inorganic phosphate is subscribed to the fast reversible exchange
      with gamma-adenosine triphosphate, which is mediated by glyceraldehyde-3
      phosphate dehydrogenase and phosphoglycerate kinase within the glycolytic
      pathway. Magn Reson Med 80:29-35, 2018. (c) 2017 The Authors Magnetic Resonance
      in Medicine published by Wiley Periodicals, Inc. on behalf of International
      Society for Magnetic Resonance in Medicine. This is an open access article under
      the terms of the Creative Commons Attribution NonCommercial License, which
      permits use, distribution and reproduction in any medium, provided the original
      work is properly cited and is not used for commercial purposes.

PMID- 29215149
TI  - Pregnancy outcomes in women on metformin for diabetes or other indications among
      those seeking teratology information services.
AB  - AIMS: Metformin is used to treat type 2 diabetes, polycystic ovary syndrome
      associated infertility, and gestational diabetes. This study aims to evaluate the
      safety of metformin in early pregnancy. METHOD: We evaluated the risk of major
      birth defects and pregnancy losses in a cohort of pregnant women exposed to
      metformin during the first trimester for different indications relative to a
      matched unexposed reference group. RESULTS: The risk of major birth defects was
      5.1% (20/392) in pregnancies exposed to metformin during the first trimester and
      2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70
      4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre
      gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared
      to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95%
      CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18
      2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was
      20.8% in women on metformin during the first trimester and 10.8% in the reference
      group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on
      metformin with and without pre-gestational diabetes were 24.0% and 16.8%
      respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74
      2.59) when compared to the reference. CONCLUSION: Pregnant women with pre
      gestational diabetes on metformin are at a higher risk for adverse pregnancy
      outcomes than the general population. This appears to be due to the underlying
      diabetes since women on metformin for other indications do not present
      meaningfully increased risks.

PMID- 29215150
TI  - MRI monitoring of focused ultrasound sonications near metallic hardware.
AB  - PURPOSE: To explore the temperature-induced signal change in two-dimensional
      multi-spectral imaging (2DMSI) for fast thermometry near metallic hardware to
      enable MR-guided focused ultrasound surgery (MRgFUS) in patients with implanted
      metallic hardware. METHOD: 2DMSI was optimized for temperature sensitivity and
      applied to monitor focus ultrasound surgery (FUS) sonications near metallic
      hardware in phantoms and ex vivo porcine muscle tissue. Further, we evaluated its
      temperature sensitivity for in vivo muscle in patients without metallic hardware.
      In addition, we performed a comparison of temperature sensitivity between 2DMSI
      and conventional proton-resonance-frequency-shift (PRFS) thermometry at different
      distances from metal devices and different signal-to-noise ratios (SNR). RESULTS:
      2DMSI thermometry enabled visualization of short ultrasound sonications near
      metallic hardware. Calibration using in vivo muscle yielded a constant
      temperature sensitivity for temperatures below 43  degrees C. For an off
      resonance coverage of +/- 6 kHz, we achieved a temperature sensitivity of
      1.45%/K, resulting in a minimum detectable temperature change of ~2.5 K for an
      SNR of 100 with a temporal resolution of 6 s per frame. CONCLUSION: The proposed
      2DMSI thermometry has the potential to allow MR-guided FUS treatments of patients
      with metallic hardware and therefore expand its reach to a larger patient
      population. Magn Reson Med 80:259-271, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29215151
TI  - Brain connectivity in children is increased by the time they spend reading books
      and decreased by the length of exposure to screen-based media.
AB  - AIM: This study compared the time spent using screen-based media or reading on
      the functional connectivity of the reading-related brain regions in children aged
      8-12. METHODS: We recruited 19 healthy American children from a private school in
      Cincinnati, USA, in 2015-6 after advertising the study to parents. The parents
      completed surveys on how many hours their children spent on independent reading
      and screen-based media time, including smartphones, tablets, desktop or laptop
      computers and television. The children underwent magnetic resonance imaging that
      assessed their resting-state connectivity between the left visual word form area,
      as the seed area, and other brain regions, with screen time and reading time
      applied as predictors. RESULTS: Time spent reading was positively correlated with
      higher functional connectivity between the seed area and left-sided language,
      visual and cognitive control regions. In contrast, screen time was related to
      lower connectivity between the seed area and regions related to language and
      cognitive control. CONCLUSION: Screen time and time spent reading showed
      different effects on functional connectivity between the visual word form area
      and language, visual and cognitive control regions of the brain. These findings
      underscore the importance of children reading to support healthy brain
      development and literacy and limiting screen time.

PMID- 29215152
TI  - Subcutaneous phaeohyphomycosis caused by Veronaea botryosa in a Japanese patient
      with adult T-cell lymphoma.

PMID- 29215153
TI  - The role of municipal public policies in oral health socioeconomic inequalities
      in Brazil: A multilevel study.
AB  - OBJECTIVES: It is known that fluoridation has a contextual effect on oral health
      socioeconomic inequalities, but broad public policies have not been investigated.
      Thus, the aim of this study was to determine the effects of municipal public
      policies on oral health across different social strata. METHODS: This was a cross
      sectional study with 7328 12-year-old children and 5445 15-19-year-old
      adolescents from 177 Brazilian municipalities. Information at municipal level was
      collated for dental services, educational services, sanitation and water
      fluoridation. The main individual-level exposure was the disposable equivalent
      household income. The dichotomous outcomes were as follows: untreated dental
      caries (>=1 tooth), missing teeth (>=1 tooth) and filled teeth (>=1 tooth).
      Analyses were carried out using multilevel logistic regression. Interaction terms
      were tested between individual-level income and policy variables. RESULTS: The
      prevalence of untreated dental caries, missing and filled teeth was 47.0%, 15.1%
      and 47.5%, respectively. There was no significant interaction between income and
      policy indicators. Individuals living in municipalities with no water
      fluoridation had 1.42 (95% CI: 1.08-1.86) higher odds of having untreated dental
      caries; the odds ratio (OR) for those in municipalities with less education
      policies was 1.36 (95% CI: 1.07-1.73); those in municipalities with less
      sanitation had OR = 1.05 (95% CI: 0.78-1.40); and those in municipalities with
      less dental care had OR = 1.36 (95% CI: 1.02-1.80). CONCLUSIONS: Fluoridation and
      policies about sanitation, education and dental care were similarly associated
      with oral health in different social strata. Other policies on social and
      economic fields may be further explored.

PMID- 29215154
TI  - Analysis of factors predicting the response to tolvaptan in patients with liver
      cirrhosis and hepatic edema.
AB  - BACKGROUND AND AIM: This study aimed to clarify the factors predictive of
      treatment response to tolvaptan (V2-receptor antagonist) for cirrhotic patients
      with hepatic edema in a real-world setting. METHODS: In this retrospective,
      multicenter study, tolvaptan was orally administered at a dose of 7.5 mg once a
      day. Patients with a decrease in body weight of 1.5 kg or greater from baseline
      were characterized as responders at day 7. RESULTS: Of 229 patients, 210 were
      subjected to this analysis. Patients consisted of 133 men and 77 women, with the
      median age of 67 years (range, 40-89 years). According to the Child-Pugh
      classification, five patients were classified as class A, 90 as class B, and 115
      as class C. The frequencies of responders and nonresponders were 55.2% and 44.8%,
      respectively. Blood urea nitrogen (BUN) level was significantly lower in
      responders compared with nonresponders (P = 3.77 * 10-3 ). Using the receiver
      operating characteristic curve, the cutoff value of 28.2 mg/dL was the most
      useful in discriminating responders from nonresponders. Among 154 patients with
      BUN level of less than 28.2 mg/dL, 95 (61.7%) were responders. By contrast, among
      56 patients with BUN level of 28.2 mg/dL or more, 21 (37.5%) were nonresponders
      (P = 2.70 * 10-3 ). On multivariate analysis, BUN level of <28.2 mg/dL and urine
      sodium >51 mEq/day were found to be independent factors associated with the
      response to tolvaptan. CONCLUSIONS: This study suggests that BUN level and
      urinary sodium excretion are closely associated with the response to tolvaptan in
      cirrhotic patients with hepatic edema.

PMID- 29215155
TI  - Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic
      review.
AB  - INTRODUCTION: The number of clinical trials investigating the optimal timing of
      prophylactic antibiotics in cesarean section has increased rapidly over the last
      few years. We conducted a systematic review to inform up-to-date evidence-based
      guidelines to prevent postpartum infectious morbidity in the mother and rule out
      any safety issues related to antepartum antibiotic exposure in infants. MATERIAL
      AND METHODS: Four bibliographic databases were searched for published reports of
      trials. Ongoing or unpublished studies were searched in Clinicaltrials.gov and
      the World Health Organization registry platform. Randomized controlled trials
      comparing antibiotic prophylaxis before and after cord clamping in cesarean
      section were eligible. Maternal and neonatal outcomes were assessed, and
      certainty of evidence graded. RESULTS: In total, 18 randomized controlled trials
      met the inclusion criteria. Those women who received antibiotics preoperatively
      were 28% (relative risk 0.72, 95% confidence interval 0.56-0.92, nine studies,
      4342 women, high quality of evidence) less likely to show infectious morbidity as
      compared with those who received antibiotics after cord clamping. The risk of
      endomyometritis and/or endometritis was reduced by 43% (relative risk 0.57, 95%
      confidence interval 0.40-0.82, 13 studies, 6250 women, high quality of evidence)
      and the risk of wound infection by 38% (relative risk 0.62, 95% confidence
      interval 0.47-0.81, 14 studies, 6450 women, high quality of evidence) in those
      who received antibiotics preoperatively as compared to those who received
      antibiotics after cord clamping. For other maternal infections no significant
      differences were identified. The risk for neonatal outcomes, such as deaths
      attributed to infection, sepsis, neonatal antibiotic treatment, intensive care
      unit admission or antibiotic-related adverse events, was not found to be
      different, either clinically or statistically, when antibiotics were given before
      or after cord clamping (moderate to low quality of evidence). CONCLUSIONS: The
      evidence in favor of prophylactic antibiotic administration before, in comparison
      with after, cord clamping for major maternal infections was of high quality,
      meaning that further research would be unlikely to change the confidence in these
      findings. However, we recommend additional research reflecting the precision of
      the effect estimates for neonatal outcomes.

PMID- 29215156
TI  - Enhanced Capacity and Rate Capability of Nitrogen/Oxygen Dual-Doped Hard Carbon
      in Capacitive Potassium-Ion Storage.
AB  - The intercalation of potassium ions into graphite is demonstrated to be feasible,
      while the electrochemical performance of potassium-ion batteries (KIBs) remains
      unsatisfying. More effort is needed to improve the specific capacity while
      maintaining a superior rate capability. As an attempt, nitrogen/oxygen dual-doped
      hierarchical porous hard carbon (NOHPHC) is introduced as the anode in KIBs by
      carbonizing and acidizing the NH2 -MIL-101(Al) precursor. Specifically, the
      NOHPHC electrode delivers high reversible capacities of 365 and 118 mA h g-1 at
      25 and 3000 mA g-1 , respectively. The capacity retention reaches 69.5% at 1050
      mA g-1 for 1100 cycles. The reasons for the enhanced electrochemical performance,
      such as the high capacity, good cycling stability, and superior rate capability,
      are analyzed qualitatively and quantitatively. Quantitative analysis reveals that
      mixed mechanisms, including capacitance and diffusion, account for the K-ion
      storage, in which the capacitance plays a more important role. Specifically, the
      enhanced interlayer spacing (0.39 nm) enables the intercalation of large K ions,
      while the high specific surface area of ~1030 m2 g-1 and the dual-heteroatom
      doping (N and O) are conducive to the reversible adsorption of K ions.

PMID- 29215158
TI  - Congenital diaphragmatic hernia with heart defect has a high risk for hypoplastic
      left heart syndrome and major extra-cardiac malformations: 10-year national
      cohort from Finland.
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) has a well-known risk of
      congenital heart defects with poor prognosis. This study was conducted to
      determine the national total prevalence and prenatal detection rates of CDH with
      heart defects and its association with major extra-cardiac malformations and to
      further evaluate the impact of the heart defect severity on survival. MATERIAL
      AND METHODS: A 10-year national cohort was derived from four national registries,
      including live births, stillbirths, and terminations of pregnancy for fetal
      anomalies. The study cohort was sorted according to cardiac defect severity.
      RESULTS: The total prevalence of CDH with heart defects was 0.6/10 000 births and
      live birth prevalence 0.3/10 000 live births. Of 145 cases with CDH, 37 (26%) had
      a concurrent heart defect. The overall prenatal detection rate of heart defects
      was 41%. The total prevalence (483/10 000) and live birth prevalence (500/10 000)
      of hypoplastic left heart syndrome were 124 and 250 times higher than in the
      general population in Finland, respectively. Additional major extra-cardiac
      malformations were found in 68% of cases. The survival rate for CDH with major
      heart defects was 11 and 38% with minor heart defects. CONCLUSIONS: The total
      prevalence of hypoplastic left heart syndrome was significantly higher in CDH
      patients than in the general population in Finland. Prenatal detection rate for
      heart defects in CDH patients was 41%. Major extra-cardiac malformations were
      more common than previously reported. The prognosis of CDH with major heart
      defects remained poor.

PMID- 29215159
TI  - Sleep disorders in obese children are not limited to obstructive sleep apnoea
      syndrome.
AB  - AIM: This study was to characterise respiratory and nonrespiratory sleep
      disorders in obese children and evaluate the diagnostic and therapeutic impact of
      a specific sleep consultation. METHODS: A descriptive study was conducted in
      obese French children who received multidisciplinary care management from the
      hospital centre for paediatric obesity in Bordeaux. This followed a specific
      sleep consultation between 2007 and 2015, because their paediatrician had
      identified symptoms suggestive of sleep disorders. RESULTS: The sleep specialist
      confirmed the presence of a sleep disorder in 98.4% of the 128 obese children,
      with a mean age of 12.1 +/- 3.2 years. These included respiratory sleep
      disorders, hypersomnolence, insomnia and circadian rhythm sleep-wake disorders.
      Polysomnography revealed that 46.1% had respiratory sleep disorders and 24.2% had
      obstructive sleep apnoea syndrome (OSAS). Just under half (47.6%) were referred
      to an otorhinolaryngologist for sleep care management, 30.5% were referred to an
      orthodontist, 17.9% had melatonin treatment and 13.3% received continuous
      positive airway pressure ventilation. CONCLUSION: Sleep disorders in obese
      children were not limited to respiratory sleep disorders including OSAS. A
      systematic specific consultation with a sleep specialist is essential for the
      diagnosis and care of such children and would be beneficial when treating
      paediatric obesity.

PMID- 29215157
TI  - Knockdown of the transcript of ERK in the brain modulates hypothalamic
      neuropeptide-mediated appetite control in amphetamine-treated rats.
AB  - BACKGROUND AND PURPOSE: Amphetamine is a releaser of dopamine stored in synaptic
      terminals, which can suppress appetite by changing the expression levels of
      neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the hypothalamus. This
      study explored whether ERKs are involved in appetite control mediated by cAMP
      response element binding protein (CREB), NPY and POMC in amphetamine-treated
      rats. EXPERIMENTAL APPROACH: Rats were given amphetamine for 4 days, and changes
      in feeding behaviour and expression levels of phosphorylated-ERK (pERK), pCREB,
      NPY and melanocortin MC3 receptors were examined and compared. KEY RESULTS:
      Following amphetamine treatment, food intake, body weight and NPY expression
      decreased, whereas the expression of pERK, pCREB, MC3 receptors and pCREB/DNA
      binding activity increased. In amphetamine-treated rats, both cerebral ERK
      knockdown and pretreatment with a peripheral dopamine receptor antagonist
      decreased NPY but increased pERK, pCREB and MC3 receptor expression. Moreover,
      the immunofluorescence of hypothalamic pERK increased following amphetamine
      treatment. CONCLUSIONS AND IMPLICATIONS: These results suggest that ERK/CREB
      signalling participates in the effects mediated by dopamine receptor/NPY/POMC on
      appetite control in rats treated with amphetamine. These findings advance the
      knowledge on the involvement of ERK/CREB signalling in the reciprocal regulation
      by NPY and POMC of appetite after amphetamine treatment.

PMID- 29215161
TI  - Suppressive oligodeoxynucleotides containing TTAGGG motifs inhibit cGAS
      activation in human monocytes.
AB  - Type I interferon (IFN) is a critical mediator of autoimmune diseases such as
      systemic lupus erythematosus (SLE) and Aicardi-Goutieres Syndrome (AGS). The
      recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production
      of type I IFN in response to cytosolic DNA and is potentially linked to SLE and
      AGS. Suppressive oligodeoxynucleotides (ODN) containing repetitive TTAGGG motifs
      present in mammalian telomeres have proven useful in the treatment of autoimmune
      diseases including SLE. In this study, we demonstrate that the suppressive ODN
      A151 effectively inhibits activation of cGAS in response to cytosolic DNA,
      thereby inhibiting type I IFN production by human monocytes. In addition, A151
      abrogated cGAS activation in response to endogenous accumulation of DNA using
      TREX1-deficient monocytes. We demonstrate that A151 prevents cGAS activation in a
      manner that is competitive with DNA. This suppressive activity of A151 was
      dependent on both telomeric sequence and phosphorothioate backbone. To our
      knowledge this report presents the first cGAS inhibitor capable of blocking self
      DNA. Collectively, these findings might lead to the development of new
      therapeutics against IFN-driven pathologies due to cGAS activation.

PMID- 29215160
TI  - New FIGO and Swedish intrapartum cardiotocography classification systems
      incorporated in the fetal ECG ST analysis (STAN) interpretation algorithm:
      agreements and discrepancies in cardiotocography classification and evaluation of
      significant ST events.
AB  - INTRODUCTION: The updated intrapartum cardiotocography (CTG) classification
      system by FIGO in 2015 (FIGO2015) and the FIGO2015-approached classification by
      the Swedish Society of Obstetricians and Gynecologist in 2017 (SSOG2017) are not
      harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007).
      The study aimed to reveal homogeneity and agreement between the systems in
      classifying CTG and ST events, and relate them to maternal and perinatal
      outcomes. MATERIAL AND METHODS: Among CTG traces with ST events, 100 traces
      originally classified as normal, 100 as suspicious and 100 as pathological were
      randomly selected from a STAN database and classified by two experts in
      consensus. Homogeneity and agreement statistics between the CTG classifications
      were performed. Maternal and perinatal outcomes were evaluated in cases with
      clinically hidden ST data (n = 151). A two-tailed p < 0.05 was regarded as
      significant. RESULTS: For CTG classes, the heterogeneity was significant between
      the old and new systems, and agreements were moderate to strong (proportion of
      agreement, kappa index 0.70-0.86). Between the new classifications, heterogeneity
      was significant and agreements strong (0.90, 0.92). For significant ST events,
      heterogeneities were significant and agreements moderate to almost perfect
      (STAN2007 vs. FIGO2015 0.86, 0.72; STAN2007 vs. SSOG2017 0.92, 0.84; FIGO2015 vs.
      SSOG2017 0.94, 0.87). Significant ST events occurred more often combined with
      STAN2007 than with FIGO2015 classification, but not with SSOG2017; correct
      identification of adverse outcomes was not significantly different between the
      systems. CONCLUSION: There are discrepancies in the classification of CTG
      patterns and significant ST events between the old and new systems. The clinical
      relevance of the findings remains to be shown.

PMID- 29215162
TI  - Delineating the association between mode of delivery and postpartum depression
      symptoms: a longitudinal study.
AB  - INTRODUCTION: Although a number of perinatal factors have been implicated in the
      etiology of postpartum depression, the role of mode of delivery remains
      controversial. Our aim was to explore the association between mode of delivery
      and postpartum depression, considering the potentially mediating or confounding
      role of several covariates. MATERIAL AND METHODS: In a longitudinal-cohort study
      in Uppsala, Sweden, with 3888 unique pregnancies followed up postpartum, the
      effect of mode of delivery (spontaneous vaginal delivery, vacuum extraction,
      elective cesarean section, emergency cesarean section) on self-reported
      postpartum depression symptoms (Edinburgh Postnatal Depression Scale >=12) at 6
      weeks postpartum was investigated through logistic regression models and path
      analysis. RESULTS: The overall prevalence of postpartum depression was 13%.
      Compared with spontaneous vaginal delivery, women who delivered by emergency
      cesarean section were at higher risk for postpartum depression 6 weeks after
      delivery in crude (odds ratio 1.45, 95% confidence interval 1.04-2.01) but not in
      adjusted analysis. However, the path analysis revealed that emergency cesarean
      section and vacuum extraction were indirectly associated with increased risk of
      postpartum depression, by leading to postpartum complications, self-reported
      physical symptoms postpartum, and therefore a negative delivery experience. In
      contrast, history of depression and fear of delivery increased the odds of
      postpartum depression and led more frequently to elective cesarean section;
      however, it was associated with a positive delivery experience. CONCLUSIONS: Mode
      of delivery has no direct impact on risk of postpartum depression; nevertheless,
      several modifiable or non-modifiable mediators are present in this association.
      Women delivering in an emergency setting by emergency cesarean section or vacuum
      extraction, and reporting negatively experienced delivery, constitute a high-risk
      group for postpartum depression.

PMID- 29215163
TI  - Transparency in the reporting of nursing research.

PMID- 29215165
TI  - Transcriptional response of Nautella italica R11 towards its macroalgal host
      uncovers new mechanisms of host-pathogen interaction.
AB  - Macroalgae (seaweeds) are essential for the functioning of temperate marine
      ecosystems, but there is increasing evidence to suggest that their survival is
      under threat from anthropogenic stressors and disease. Nautella italica R11 is
      recognized as an aetiological agent of bleaching disease in the red alga, Delisea
      pulchra. Yet, there is a lack of knowledge surrounding the molecular mechanisms
      involved in this model host-pathogen interaction. Here we report that mutations
      in the gene encoding for a LuxR-type quorum sensing transcriptional regulator,
      RaiR, render N. italica R11 avirulent, suggesting this gene is important for
      regulating the expression of virulence phenotypes. Using an RNA sequencing
      approach, we observed a strong transcriptional response of N. italica R11 towards
      the presence of D. pulchra. In particular, genes involved in oxidative stress
      resistance, carbohydrate and central metabolism were upregulated in the presence
      of the host, suggesting a role for these functions in the opportunistic
      pathogenicity of N. italica R11. Furthermore, we show that RaiR regulates a
      subset of genes in N. italica R11, including those involved in metabolism and the
      expression of phage-related proteins. The outcome of this research reveals new
      functions important for virulence of N. italica R11 and contributes to our
      greater understanding of the complex factors mitigating microbial diseases in
      macroalgae.

PMID- 29215164
TI  - Magnetically Guided Self-Assembly and Coding of 3D Living Architectures.
AB  - In nature, cells self-assemble at the microscale into complex functional
      configurations. This mechanism is increasingly exploited to assemble biofidelic
      biological systems in vitro. However, precise coding of 3D multicellular living
      materials is challenging due to their architectural complexity and spatiotemporal
      heterogeneity. Therefore, there is an unmet need for an effective assembly method
      with deterministic control on the biomanufacturing of functional living systems,
      which can be used to model physiological and pathological behavior. Here, a
      universal system is presented for 3D assembly and coding of cells into complex
      living architectures. In this system, a gadolinium-based nonionic paramagnetic
      agent is used in conjunction with magnetic fields to levitate and assemble cells.
      Thus, living materials are fabricated with controlled geometry and organization
      and imaged in situ in real time, preserving viability and functional properties.
      The developed method provides an innovative direction to monitor and guide the
      reconfigurability of living materials temporally and spatially in 3D, which can
      enable the study of transient biological mechanisms. This platform offers broad
      applications in numerous fields, such as 3D bioprinting and bottom-up tissue
      engineering, as well as drug discovery, developmental biology, neuroscience, and
      cancer research.

PMID- 29215166
TI  - Effectiveness of platelet-rich plasma therapy in wound healing of pilonidal sinus
      surgery: A comprehensive systematic review and meta-analysis.
AB  - Pilonidal disease (PD) is a chronic situation which may cause pain, discomfort,
      inflammation, discharges, and inability to do daily routines. Among two main
      methods of surgery, open healing is preferred by surgeons since it associates
      with lower risk of recurrence; however, it could complicate the wound condition
      by delaying the healing process. For this meta-analysis, a search in Medline,
      Embase, and Scopus was performed in June 2017 with no restrictions placed on the
      publication date or languages. Then, time to healing was considered as the effect
      size and all the data from trials were extracted. The heterogeneity and the
      variation in pooled estimation were assessed using Cochran's Q test and I
      squared, respectively. Meta-regression was used to examine the relationship
      between the effect size and year, studies' sample sizes, proportion of male
      gender and age with the cause of heterogeneity. From 11 selected articles finally
      4 met our inclusion and exclusion criteria with the total number of 484 patients.
      Using a fixed-effect model, pool effect was detected 0.642 (95% CI: 0.485-0.798).
      A homogeneity of pooled effect size estimate for the studies was also found
      (Cochran Q test, p-value = 0.844, I-square = 0.0%). Moreover, results of meta
      regression showed no statistically significant association between the effect
      size and patients' mean age, year of publication, total sample size, and sex
      proportion (0.51 < p-values < 0.98). Platelet-rich plasma therapy for PD wounds
      appeared more effective than classic wound dressing.

PMID- 29215167
TI  - Plasmonic Metaparticles on a Blackbody Create Vivid Reflective Colors for Naked
      Eye Environmental and Clinical Biodetection.
AB  - Plasmonic dipoles are famous for their strong absorptivity rather than their
      reflectivity. Here, the as-yet unknown specular reflection and the Brewster
      effect of ultrafine plasmonic dipoles, metaparticles, are introduced and
      exploited as the basis of new design rules for advanced applications. A
      configuration of "Plasmonic metaparticles on a blackbody" is demonstrated and
      utilized for the design of a tailored perfect-colored absorber and for visual
      detection of environmental dielectrics that is not readily done by extinction
      plasmonics. Moreover, the Plasmonic Brewster Wavelength (PBW) effect is
      introduced as a new platform for the naked-eye and bulk biodetection of analytes.
      The technique operates based on slight changes of molecular polarizability which
      is not detectable via conventional plasmon resonance techniques. As a specific
      highlight, the clinical applicability of the PBW method is demonstrated while
      addressing the transduction plasmonic techniques' challenge in detection of bulk
      refractive index changes of the healthy and diseased human serum exosomes.
      Finally, the sputtering-based fabrication method used here is simple,
      inexpensive, and scalable, and does not require the sophisticated patterning
      approach of lithography or precise alignment of light coupling for the
      biodetection.

PMID- 29215168
TI  - Decreased Signal Intensity Ratio on MRA Reflects Misery Perfusion on SPECT in
      Patients with Intracranial Stenosis.
AB  - BACKGROUND AND PURPOSE: Acetazolamide reactivity on 123 I-IMP SPECT is used to
      detect misery perfusion due to intracranial atherosclerosis. Noninvasive
      fractional flow assessed by signal intensity ratio (SIR) on time of flight
      magnetic resonance angiography (TOF-MRA) might offer a feasible alternative to
      identify high-risk intracranial stenosis. METHODS: Data from consecutive patients
      with unilateral middle cerebral artery (MCA) stenosis who underwent both TOF-MRA
      and acetazolamide reactivity on 123 I-IMP SPECT were retrospectively analyzed.
      Signal intensity was measured in the background and on the MCA proximal and
      distal to the stenotic lesion on TOF-MRA. Mean cerebral blood flow (CBF) at rest
      and cerebrovascular reactivity were measured in the target MCA territory. CBF
      patterns of the MCA were divided into three groups (Powers' stage 0-II). RESULTS:
      A total of 56 sets of diagnostic imaging in 33 patients were assessed. Four CBF
      patterns were stage II in four MCA territories, stage I in 31, and stage 0 in 21.
      Median SIR of the MCA was .53 (interquartile range .46-.69) for stage II, .78
      (.63-.90) for stage I, and .91 (.85-.95) for stage 0. The optimal cutoff for SIR
      obtained from receiver operating characteristic curve analysis to predict stage
      II was < .56. CONCLUSIONS: In patients with unilateral MCA stenosis, decreased
      SIR was correlated with misery perfusion, providing a simpler, widely available
      predictor of high-risk intracranial stenosis.

PMID- 29215169
TI  - Stimulation of PgdA-dependent peptidoglycan N-deacetylation by GpsB-PBP A1 in
      Listeria monocytogenes.
AB  - Listeria monocytogenes and other pathogenic bacteria modify their peptidoglycan
      to protect it against enzymatic attack through the host innate immune system,
      such as the cell wall hydrolase lysozyme. During our studies on GpsB, a late cell
      division protein that controls activity of the bi-functional penicillin binding
      protein PBP A1, we discovered that GpsB influences lysozyme resistance of L.
      monocytogenes as mutant strains lacking gpsB showed an increased lysozyme
      resistance. Deletion of pbpA1 corrected this effect, demonstrating that PBP A1 is
      also involved in this. Susceptibility to lysozyme mainly depends on two
      peptidoglycan modifying enzymes: The peptidoglycan N-deacetylase PgdA and the
      peptidoglycan O-acetyltransferase OatA. Genetic and biochemical experiments
      consistently demonstrated that the increased lysozyme resistance of the DeltagpsB
      mutant was PgdA-dependent and OatA-independent. Protein-protein interaction
      studies supported the idea that GpsB, PBP A1 and PgdA form a complex in L.
      monocytogenes and identified the regions in PBP A1 and PgdA required for complex
      formation. These results establish a physiological connection between GpsB, PBP
      A1 and the peptidoglycan modifying enzyme PgdA. To our knowledge, this is the
      first reported link between a GpsB-like cell division protein and factors
      important for escape from the host immune system.

PMID- 29215171
TI  - Graphene Inks as Versatile Templates for Printing Tiled Metal Oxide Crystalline
      Films.
AB  - There is great interest in exploiting van der Waals gaps in layered materials as
      confinement reaction vessels to template the synthesis of new nanosheet
      structures. The gallery spaces in multilayer graphene oxide, for example, can
      intercalate hydrated metal ions that assemble into metal oxide films during
      thermal oxidation of the sacrificial graphene template. This approach offers
      limited control of structure, however, and does not typically lead to 2D atomic
      scale growth of anisotropic platelet crystals, but rather arrays of simple
      particles directionally sintered into porous sheets. Here, a new graphene
      directed assembly route is demonstrated that yields fully dense, space-filling
      films of tiled metal oxide platelet crystals with tessellated structures. The
      method relies on colloidal engineering to produce a printable "metallized
      graphene ink" with accurate control of metal loading, grain size/porosity,
      composition, and micro/nanomorphologies, and is capable of achieving higher metal
      carbon ratio than is possible by intercalation methods. These tiled structures
      are sufficiently robust to create free standing papers, complex microtextured
      films, 3D shapes, and metal oxide replicas of natural biotextures.

PMID- 29215170
TI  - Synthetic Light-Curable Polymeric Materials Provide a Supportive Niche for Dental
      Pulp Stem Cells.
AB  - Dental disease annually affects billions of patients, and while regenerative
      dentistry aims to heal dental tissue after injury, existing polymeric restorative
      materials, or fillings, do not directly participate in the healing process in a
      bioinstructive manner. There is a need for restorative materials that can support
      native functions of dental pulp stem cells (DPSCs), which are capable of
      regenerating dentin. A polymer microarray formed from commercially available
      monomers to rapidly identify materials that support DPSC adhesion is used. Based
      on these findings, thiol-ene chemistry is employed to achieve rapid light-curing
      and minimize residual monomer of the lead materials. Several triacrylate bulk
      polymers support DPSC adhesion, proliferation, and differentiation in vitro, and
      exhibit stiffness and tensile strength similar to existing dental materials.
      Conversely, materials composed of a trimethacrylate monomer or bisphenol A
      glycidyl methacrylate, which is a monomer standard in dental materials, do not
      support stem cell adhesion and negatively impact matrix and signaling pathways.
      Furthermore, thiol-ene polymerized triacrylates are used as permanent filling
      materials at the dentin-pulp interface in direct contact with irreversibly
      injured pulp tissue. These novel triacrylate-based biomaterials have potential to
      enable novel regenerative dental therapies in the clinic by both restoring teeth
      and providing a supportive niche for DPSCs.

PMID- 29215173
TI  - When do trade-offs occur? The roles of energy constraints and trait flexibility
      in bushcricket populations.
AB  - In many animal species, the expression of sexually selected traits is negatively
      correlated with traits associated with survival such as immune function, a
      relationship termed a 'trade-off'. But an alternative in which sexually selected
      traits are positively correlated with survival traits is also widespread. We
      propose that the nature of intertrait relationships is largely determined by
      overall energy expenditure, energy availability and trait flexibility, with trade
      offs expected when individuals are subject to energy constraints. We tested this
      hypothesis in Ephippiger diurnus, a European bushcricket in which males are
      distinguished by two prominent sexually selected traits, acoustic calls and a
      large spermatophore transferred to the female at mating, and where immune
      function may be critical in survival. Ephippiger diurnus are distributed as
      small, isolated populations that are differentiated genetically and
      behaviourally. We analysed songs, spermatophores and the immune function in male
      individuals from eight populations spanning a range of song types. As predicted,
      we only found trade-offs in those populations that expended more energy on song
      and were less flexible in their ability to adjust that expenditure. Ultimately,
      energy constraints and resulting trade-offs may limit the evolution of song
      exaggeration in E. diurnus populations broadcasting long calls comprised of
      multiple 'syllables'.

PMID- 29215172
TI  - Fibroblast growth factor 21 increases hepatic oxidative capacity but not physical
      activity or energy expenditure in hepatic peroxisome proliferator-activated
      receptor gamma coactivator-1alpha-deficient mice.
AB  - NEW FINDINGS: What is the central question of this study? Does a reduction in
      hepatic peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha), which has been observed in an insulin-resistant obese state, impair the
      ability of fibroblast growth factor 21 (FGF21) to modulate metabolism? What is
      the main finding and its importance? A deficit in hepatic PGC-1alpha does not
      compromise the ability of FGF21 to increase hepatic fatty acid oxidation;
      however, the effects of FGF21 to regulate whole-body metabolism (i.e. total and
      resting energy expenditure), as well as ambulatory activity, were altered when
      hepatic PGC-1alpha was reduced. ABSTRACT: Fibroblast growth factor 21 (FGF21)
      treatment drives metabolic improvements, including increased metabolic flux and
      reduced hepatic steatosis, but the mechanisms responsible for these effects
      remain to be elucidated fully. We tested whether a targeted reduction in hepatic
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha),
      which has been shown to occur with obesity, had a negative impact on the
      metabolic effects of FGF21. We infused FGF21 (1 mg kg-1  day-1 ) or saline in
      chow-fed wild-type (WT) and liver-specific PGC-1alpha heterozygous (LPGC-1alpha)
      mice for 4 weeks. Administration of FGF21 lowered serum insulin and cholesterol
      (P <= 0.05) and tended to lower free fatty acids (P = 0.057). The LPGC-1alpha
      mice exhibited reduced complete hepatic fatty acid oxidation (FAO; LPGC-1alpha,
      1788 +/- 165 nmol g-1  h-1 compared with WT, 2572 +/- 437 nmol g-1  h-1 ; P <
      0.001), which was normalized by FGF21 treatment (2788 +/- 519 nmol g-1  h-1 ; P <
      0.001). FGF21 also increased hepatic incomplete FAO by 12% in both groups and
      extramitochondrial FAO by 89 and 56% in WT and LPGC-1alpha mice, respectfully (P
      = 0.001), and lowered hepatic triacylglycerol by 30-40% (P < 0.001). Chronic
      treatment with FGF21 lowered body weight and fat mass (P < 0.05), while
      increasing food consumption (P < 0.05), total energy expenditure [7.3 +/- 0.60
      versus 6.6 +/- 0.39 kcal (12 h)-1 in WT mice; P = 0.009] and resting energy
      expenditure [5.4 +/- 0.89 versus 4.6 +/- 0.21 kcal (12 h)-1 in WT mice; P =
      0.005]. Interestingly, FGF21 only increased ambulatory activity in the WT mice (P
      = 0.03), without a concomitant increase in non-resting energy expenditure. In
      conclusion, although reduced hepatic PGC-1alpha expression was not necessary for
      FGF21 to increase FAO, it does appear to mediate FGF21-induced changes in total
      and resting energy expenditure and ambulatory activity in lean mice.

PMID- 29215174
TI  - Microscale 3D Printing of Nanotwinned Copper.
AB  - Nanotwinned (nt)-metals exhibit superior mechanical and electrical properties
      compared to their coarse-grained and nanograined counterparts. nt-metals in film
      and bulk forms are obtained using physical and chemical processes including
      pulsed electrodeposition (PED), plastic deformation, recrystallization, phase
      transformation, and sputter deposition. However, currently, there is no process
      for 3D printing (additive manufacturing) of nt-metals. Microscale 3D printing of
      nt-Cu is demonstrated with high density of coherent twin boundaries using a new
      room temperature process based on localized PED (L-PED). The 3D printed nt-Cu is
      fully dense, with low to none impurities, and low microstructural defects, and
      without obvious interface between printed layers, which overall result in good
      mechanical and electrical properties, without any postprocessing steps. The L-PED
      process enables direct 3D printing of layer-by-layer and complex 3D microscale nt
      Cu structures, which may find applications for fabrication of metamaterials,
      sensors, plasmonics, and micro/nanoelectromechanical systems.

PMID- 29215176
TI  - Protective role of the HOG pathway against the growth defect caused by impaired
      biosynthesis of complex sphingolipids in yeast Saccharomyces cerevisiae.
AB  - Complex sphingolipids play critical roles in various cellular events in the yeast
      Saccharomyces cerevisiae. To identify genes that are related to the growth defect
      caused by disruption of complex sphingolipid biosynthesis, we screened for
      suppressor mutations and multicopy suppressor genes that confer resistance
      against repression of AUR1 encoding inositol phosphorylceramide synthase. From
      the results of this screening, we found that the activation of high-osmolarity
      glycerol (HOG) pathway is involved in suppression of growth defect caused by
      impaired biosynthesis of complex sphingolipids. Furthermore, it was found that
      transcriptional regulation via Msn2, Msn4 and Sko1 is involved in the suppressive
      effect of the HOG pathway. Lack of the HOG pathway did not enhance the reductions
      in complex sphingolipid levels or the increase in ceramide level caused by the
      AUR1 repression, implying that the suppressive effect of the HOG pathway on the
      growth defect is not attributed to restoration of impaired biosynthesis of
      complex sphingolipids. On the contrary, the HOG pathway and Msn2/4-mediated
      transcriptional activation was involved in suppression of aberrant reactive
      oxygen species accumulation caused by the AUR1 repression. These results
      indicated that the HOG pathway plays pivotal roles in maintaining cell growth
      under impaired biosynthesis of complex sphingolipids.

PMID- 29215175
TI  - Mesoporous Metal-Organic Frameworks with Exceptionally High Working Capacities
      for Adsorption Heat Transformation.
AB  - Pore size is one of the most important parameters of adsorbents, and mesoporous
      materials have received intense attention for large guests. Here, a series of
      mesoporous coordination polymers underlying a new framework prototype for fast
      expansion of pore size is reported and the profound effect of pore size on
      adsorption heat transformation is demonstrated. Three isostructural honeycomb
      like frameworks are designed and synthesized by combining ditopic linear metal
      oxalate chains and triangular tris-pyridine ligands. Changing the ligand bridging
      length from 5.5 to 8.6 and 9.9 A gives rise to effective pore diameter from 20 to
      33 and 37 A, surface area from 2096 to 2630 and 2749 m2 g-1 , and pore volume
      from 1.19 to 1.93 and 2.36 cm3 g-1 , respectively. By virtue of the unique and
      tunable isotherm shape of mesopores, exceptionally large working capacity up to
      1.19 g g-1 or 0.38 g cm-3 for adsorption heat transformation can be achieved
      using R-134a (1,1,1,2-tetrafluroethane) as a working fluid.

PMID- 29215177
TI  - Scleral suture fixation of supplementary sulcus-based toric intraocular lenses to
      prevent rotational instability.

PMID- 29215178
TI  - Predictors of visual outcome and the role of early vitrectomy in streptococcal
      endophthalmitis: response.

PMID- 29215179
TI  - Five-year visual outcome among people with correctable visual impairment: the
      Liwan Eye Study.
AB  - IMPORTANCE: Longitudinal data on visual outcome of correctable visual impairments
      (VI) are of paramount importance for decision-maker to estimate burden and demand
      to treat avoidable VI. BACKGROUND: To assess the 5-year visual outcome among
      participants with correctable VI and to identify associated risk factors. DESIGN:
      Population-based longitudinal cohort study. PARTICIPANTS: Participants with
      correctable VI at baseline attended the 5-year follow-up visit of the Liwan Eye
      Study. METHODS: Presenting visual acuity (PVA) with habitual refractive
      correction was assessed using an Early Treatment Diabetic Retinopathy Study
      (ETDRS) chart. Then participants with PVA <6/12 in either eye underwent further
      non-cycloplegic subjective refraction to obtain their best-corrected visual
      acuity. Correctable VI was defined as having a PVA of <6/12 in the better eye
      which could be improved to >=6/12 after refractive correction. MAIN OUTCOME
      MEASURES: The 5-year visual outcome among participants with correctable VI.
      RESULTS: Among 1405 participants at baseline examination, 188 (13.4%) had
      correctable VI, of whom 118 (62.8%) were re-examined at the 5-year follow-up,
      including 39 (33.9%) who progressed to non-correctable VI, 43 (37.4%) who had
      persistent correctable VI and 33 (28.7%) who were converted to normal vision. In
      multivariate logistic regression, compared with participants who were no longer
      visual impaired, significant risk factors for participants with persistent VI
      were older, had income <1000 RMB/month, and more myopia spherical equivalent.
      CONCLUSIONS AND RELEVANCE: Over two of three participants with correctable VI
      remained to have VI after 5 years, among whom 50% are correctable by spectacles,
      highlighting the need to improve the refractive care accessibility to treat
      avoidable VI in China.

PMID- 29215180
TI  - Direct and indirect costs incurred by Australian living kidney donors.
AB  - AIM: To describe the direct and indirect costs incurred by Australian living
      kidney donors. METHODS: A total of 55 living kidney donors from three centres in
      Perth, Australia and one centre in Melbourne, Australia (2010-2014) was studied.
      Forty-nine donors provided information on expenses incurred during the donor
      evaluation period and up to 3 months after donation. A micro-costing approach was
      used to measure and value the units of resources consumed. Expenses were grouped
      as direct costs (ground and air travel, accommodation, and prescription
      medications) and indirect costs (lost wages and lost productivity). Costs were
      standardized to the year 2016 in Australian dollars. RESULTS: The most common
      direct costs were for ground travel (100%), parking (76%), and post-donation pain
      medications or antibiotics (73%). The highest direct costs were for air travel
      (median $1986 [three donors]) and ground travel (median $459 [49 donors]). Donors
      also reported lost wages (median $9891 [37 donors]). The inability to perform
      household activities or care for dependants were reported by 32 (65%) and 23
      (47%) donors. Total direct costs averaged $1682 per donor (median $806 among 49
      donors). Total indirect costs averaged $7249 per donor (median $7273 among 49
      donors). Total direct and indirect costs averaged $8932 per donor (median $7963
      among 49 donors). CONCLUSION: Many Australian living kidney donors incur
      substantial costs during the donation process. Our findings inform the continued
      development of policies and programmes designed to minimize costs incurred by
      living kidney donors.

PMID- 29215181
TI  - Ruthenium(II)-Catalyzed C-H Difluoromethylation of Ketoximes: Tuning the
      Regioselectivity from the meta to the para Position.
AB  - A highly para-selective CAr -H difluoromethylation of ketoxime ethers under
      ruthenium catalysis has been developed. A wide variety of ketoxime ethers are
      compatible with the reaction, which leads to the corresponding para
      difluoromethylated products in moderate to good yield. A mechanistic study
      clearly showed that chelation-assisted cycloruthenation is the key factor in the
      para selectivity of the difluoromethylation of ketoxime ethers. Density
      functional theory was used to gain a theoretical understanding of the para
      selectivity.

PMID- 29215182
TI  - Biomass smoke COPD: A phenotype or a different disease?

PMID- 29215184
TI  - A Single Mutation Increases the Activity and Stability of Pectobacterium
      carotovorum Nitrile Reductase.
AB  - Nitrile reductases are considered to be promising and environmentally benign
      nitrile-reducing biocatalysts to replace traditional metal catalysts.
      Unfortunately, the catalytic efficiencies of the nitrile reductases reported so
      far are very low. To date, all attempts to increase the catalytic activity of
      nitrile reductases by protein engineering have failed. In this work, we
      successfully increased the specific activity of a nitrile reductase from
      Pectobacterium carotovorum from 354 to 526 U gprot-1 by engineering the substrate
      binding pocket; moreover, the thermostability was also improved (~2-fold),
      showing half-lives of 140 and 32 h at 30 and 40  degrees C, respectively. In the
      bioreduction of 2-amino-5-cyanopyrrolo[2,3-d]pyrimidin-4-one (preQ0 ) to 2-amino
      5-aminomethylpyrrolo[2,3-d]pyrimidin-4-one (preQ1 ), the variant was advantageous
      over the wild-type enzyme with a higher reaction rate and complete conversion of
      the substrate within a shorter period. Homology modeling and docking analysis
      revealed some possible origins of the increased activity and stability. These
      results establish a solid basis for future engineering of nitrile reductases to
      increase the catalytic efficiency further, which is a prerequisite for applying
      these novel biocatalysts in synthetic chemistry.

PMID- 29215183
TI  - Use of biological drugs in patients with psoriasis and psoriatic arthritis in
      Italy: Results from the PSONG survey.
AB  - This Italian multicenter retrospective study compared the drug survival and
      efficacy of different anti-TNF agents in psoriasis (PsO) and psoriatic arthritis
      (PsA) patients. A database of PsO/PsA patients treated with adalimumab,
      etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90,
      and 100 was calculated at each time point to evaluate efficacy. Drug survival
      rate and probability of maintaining PASI response were evaluated. The impact of
      dependent variables on probability of PASI 75 loss was evaluated by logistic
      regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest
      survival rates were observed with adalimumab followed by etanercept and
      infliximab in PsO and PsA patients. The probability of maintaining PASI response
      was significantly higher for adalimumab followed by infliximab. For PsO patients,
      the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1;
      95% CI: 4.2-15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6-16.3, p < .001)
      vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher
      in etanercept-treated patients (OR: 2.3; 95% CI: 1.4-3.8, p = .01) or infliximab
      (OR: 2.2; 95% CI: 1.1-4.1, p = .018) vs. adalimumab. Adalimumab could be the best
      therapeutic option over other anti-TNF agents for the treatment of PsO and PsA
      patients.

PMID- 29215185
TI  - Potential of autologous adipose-derived stem cells to regenerate atrophied muscle
      in a rat model.
AB  - Muscle atrophy results in severe functional impairment and is a significant
      clinical problem. We examined and characterized the therapeutic effects of
      autologous adipose-derived stem cells (ADSCs) using an in vivo muscle atrophy rat
      model. To identify the effect of injected ADSCs into muscle, we developed the
      following two models of muscle atrophy in rats: induction of denervation by
      sciatic nerve defects; and nerve repair after severing the sciatic nerve. The
      inguinal fat pads were harvested from each rat and autologous ADSCs were cultured
      and ADSCs were injected in the right hind limbs as the experimental group, while
      normal saline was injected in the left hind limbs, which served as the control
      group. After 2 weeks, gross examination and histologic analyses were performed.
      Additionally, to investigate the survival of ADSCs in muscle tissues, we traced
      the injected ADSCs. The fate of injected ADSCs into muscle was investigated using
      a green fluorescent protein (GFP) tagging method with lentivirus transfection.
      The muscle weight and cross-sectional area of muscle were greater and
      proliferation of connective tissue was less prominent in the ADSC-injected group.
      Alpha-bungarotoxin binding in the neuromuscular junction was significantly
      increased, and neoangiogenesis was higher in the ADSCs-injected group. green
      fluorescent protein-labeled ADSCs survived in the gastrocnemius muscle after 2
      weeks. These findings could give a support in finding the role of autologous
      ADSCs as new therapeutic modality for regeneration of atrophied muscle.

PMID- 29215186
TI  - A General Approach Towards Triazole-Linked Adenosine Diphosphate Ribosylated
      Peptides and Proteins.
AB  - Current methods to prepare adenosine diphosphate ribosylated (ADPr) peptides are
      not generally applicable due to the labile nature of this post-translational
      modification and its incompatibility with strong acidic conditions used in
      standard solid-phase peptide synthesis. A general strategy is presented to
      prepare ADPr peptide analogues based on a copper-catalyzed click reaction between
      an azide-modified peptide and an alkyne-modified ADPr counterpart. The scope of
      this approach was expanded to proteins by preparing two ubiquitin ADPr analogues
      carrying the biological relevant alpha-glycosidic linkage. Biochemical validation
      using Legionella effector enzyme SdeA shows that clicked ubiquitin ADPr is well
      tolerated and highlights the potential of this strategy to prepare ADPr proteins.

PMID- 29215187
TI  - The use of orientation/decision/do/discuss/reflect (OD3R) method to increase
      critical thinking skill and practical skill in biochemistry learning.
AB  - We have developed an OD3R method that can be applied on Biochemistry learning.
      This OD3R consists of 5 phases: orientation, decision, do, discuss, and reflect
      to connect lessons in the class with practice in the laboratory. Implementation
      of OD3R method was done in 2 universities in Yogyakarta to increase critical
      thinking skill and practical skill of the students. The critical thinking skills
      were assessed using modified Hoyo rubric according to student's ability in
      writing laboratory work report. Practical skill was assessed using a rubric with
      6 practical skill categories: procedural skill, manipulative skill, observation
      skill, drawing skill, interpretation skill, and presentation skill.
      Implementation result shows that OD3R method can increase critical thinking skill
      and practical skill of the students. OD3R method is a learning method that is
      centered on the students and can be recommended to train thinking skill and
      practical skill of students in University. (c) 2017 by The International Union of
      Biochemistry and Molecular Biology, 46(2):107-113, 2018.

PMID- 29215188
TI  - Polymerase chain reaction test in induced sputum of patients with pulmonary
      tuberculosis.
AB  - INTRODUCTION: Induced sputum (IS) is an alternative method of obtaining sputum,
      but IS smears are frequently negative. Culture is more time consuming in its
      results, and less useful to guide the diagnosis. Polymerase chain reaction (PCR)
      is the most common methodology for rapid diagnosis of tuberculosis (TB), and few
      studies evaluated its role in IS samples. OBJECTIVES: The objective of this study
      is to determine the diagnostic yield of PCR for TB compared with culture in IS
      samples. MATERIALS AND METHODS: Prospective study. Inpatients and outpatients of
      >18 years with respiratory symptoms suggestive of PTB were invited to
      participate. The subjects were interviewed using a standardized questionnaire,
      and collected IS. Three samples were obtained for AFB smear and culture. A fourth
      sample was obtained for PCR test. RESULTS: A total of 116 IS samples were
      evaluated. The sensitivity, specificity, positive predictive value and negative
      predictive values of PCR were 95.2%, 48.4%, 29.0% and 97.9%, respectively. The
      area under the receiver operating characteristic curve was .72 for the PCR test
      (P < .0001). CONCLUSIONS: Although the PCR specificity could be underestimated,
      if we consider PCR to be more sensitive than the culture method used, we believed
      that these PCR-positive tests mean false positives. The results of PCR should
      always be interpreted carefully in conjunction with clinical information.

PMID- 29215190
TI  - Organohalide respiration in pristine environments: implications for the natural
      halogen cycle.
AB  - Halogenated organic compounds, also termed organohalogens, were initially
      considered to be of almost exclusively anthropogenic origin. However, over 5000
      naturally synthesized organohalogens are known today. This has also fuelled the
      hypothesis that the natural and ancient origin of organohalogens could have
      primed development of metabolic machineries for their degradation, especially in
      microorganisms. Among these, a special group of anaerobic microorganisms was
      discovered that could conserve energy by reducing organohalogens as terminal
      electron acceptor in a process termed organohalide respiration. Originally
      discovered in a quest for biodegradation of anthropogenic organohalogens, these
      organohalide-respiring bacteria (OHRB) were soon found to reside in pristine
      environments, such as the deep subseafloor and Arctic tundra soil with limited/no
      connections to anthropogenic activities. As such, accumulating evidence suggests
      an important role of OHRB in local natural halogen cycles, presumably taking
      advantage of natural organohalogens. In this minireview, we integrate current
      knowledge regarding the natural origin and occurrence of industrially important
      organohalogens and the evolution and spread of OHRB, and describe potential
      implications for natural halogen and carbon cycles.

PMID- 29215189
TI  - Dapagliflozin as add-on therapy in Asian patients with type 2 diabetes
      inadequately controlled on insulin with or without oral antihyperglycemic drugs:
      A randomized controlled trial.
AB  - BACKGROUND: This 24-week Phase 3 double-blind placebo-controlled study assessed
      the safety and efficacy of dapagliflozin as add-on to insulin, with or without
      oral antihyperglycemic drugs (OADs), in Asian patients with inadequately
      controlled type 2 diabetes mellitus. METHODS: Adult patients with HbA1c between
      >=7.5% and <=10.5%, body mass index <=45 kg/m2 , and on insulin doses >=20 IU
      daily were randomized to dapagliflozin 10 mg (n = 139) or placebo (n = 133) to
      assess 24-week changes in HbA1c (primary outcome), fasting plasma glucose (FPG),
      body weight, total daily dose of insulin (TDDI), and seated systolic blood
      pressure (SeSBP; exploratory outcome). RESULTS: Baseline characteristics were
      similar in both groups. At Week 24, compared with placebo, dapagliflozin
      significantly improved HbA1c (mean [95% confidence interval] 0.03% [-0.11, 0.17]
      for placebo vs -0.87% [-1.00, -0.74] for dapagliflozin; between-group difference 
      0.90% [-1.09, -0.71], P < 0.0001]), FPG, body weight, TDDI, and SeSBP. The
      incidence of adverse events (AEs) in the dapagliflozin and placebo groups was
      80.5% and 71.2%, respectively, with few patients discontinuing due to AEs
      (dapagliflozin, 2.2%; placebo, 4.2%). The occurrence of hypoglycemia was similar
      in the dapagliflozin and placebo groups (23.7% and 22.6%, respectively; no major
      events). The frequency of urinary tract and genital infections was low; no deaths
      were reported. CONCLUSIONS: Dapagliflozin as add-on to insulin, with or without
      OADs, significantly improved glycemic control and reduced body weight and blood
      pressure in Asian patients. Dapagliflozin was well tolerated, with a similar
      frequency of hypoglycemia in both groups. These results support the use of
      dapagliflozin as add-on to insulin, with or without OADs, in this population.

PMID- 29215191
TI  - Comparison of two different techniques of cooperative learning approach:
      Undergraduates' conceptual understanding in the context of hormone biochemistry.
AB  - The purpose of the research was to compare the effects of two different
      techniques of the cooperative learning approach, namely Team-Game Tournament and
      Jigsaw, on undergraduates' conceptual understanding in a Hormone Biochemistry
      course. Undergraduates were randomly assigned to Group 1 (N = 23) and Group 2 (N
      = 29). Instructions were accomplished using Team-Game Tournament in Group 1 and
      Jigsaw in Group 2. Before the instructions, all groups were informed about
      cooperative learning and techniques, their responsibilities in the learning
      process and accessing of resources. Instructions were conducted under the
      guidance of the researcher for nine weeks and the Hormone Concept Test developed
      by the researcher was used before and after the instructions for data collection.
      According to the results, while both techniques improved students' understanding,
      Jigsaw was more effective than Team-Game Tournament. (c) 2017 by The
      International Union of Biochemistry and Molecular Biology, 46(2):114-120, 2018.

PMID- 29215192
TI  - Forest conversion induces seasonal variation in microbial beta-diversity.
AB  - World-wide conversion of natural forests to other land uses has profound effects
      on soil microbial communities. However, how soil microbial beta-diversity
      responds to land-use change and its driving mechanisms remains poorly understood.
      In this study, therefore, we examined the effect of forest conversion from native
      broad-leaved forest to coniferous plantation on soil microbial beta-diversity and
      its underlying mechanisms in both summer and winter in subtropical China.
      Microbial communities increasingly differed in structure as geographical distance
      between them increased, and the slope of the relationship among distances and
      community similarity differed among forest covers. In general, as with microbial
      beta-diversity, slopes also shifted across seasons. Finally, null deviations of
      bacterial and fungal communities were lower in coniferous plantation and
      presented opposing seasonal variations with greater influences of deterministic
      processes in summer for soil fungi and in winter for soil bacteria. Integrating
      previous frameworks with our beta-null model results, we propose a conceptual
      model to link microbial secondary succession to stochastic/deterministic shifts
      in forest ecosystems. Overall, forest conversion induced significant increases in
      stochastic processes in both bacterial and fungal community assemblies.
      Therefore, our results highlight the importance of spatiotemporal scales to
      assess the influence of land-use change on microbial beta-diversity.

PMID- 29215194
TI  - Citrate, low pH and amino acid limitation induce citrate utilization in
      Lactococcus lactis biovar diacetylactis.
AB  - In Lactococcus lactis subsp. lactis biovar diacetylactis, citrate transport is
      facilitated by the plasmid-encoded citrate permease (CitP). In this work, we
      analysed regulation of citrate utilization by pH, nutrient limitation and the
      presence of citrate at four different levels: (i) plasmid copy number, (ii) citP
      transcription, (iii) citP mRNA processing and (iv) citrate utilization capacity.
      Citrate was supplied as cosubstrate together with lactose. The citP gene is known
      to be induced in cells grown at low pH. However, we demonstrated that
      transcription of citP was even higher in the presence of citrate (3.8-fold
      compared with 2.0-fold). The effect of citrate has been overlooked by other
      researchers because they determined the effect of citrate using M17 medium, which
      already contains 0.80 +/- 0.07 mM citrate. The plasmid copy number increased in
      cells grown under amino acid limitation (1.6-fold) and/or at low pH (1.4-fold).
      No significant differences in citP mRNA processing were found. Citrate
      utilization rates increased from approximately 1 to 65 MUmol min-1  gDW-1 from
      lowest to highest citP expression. Acetoin formation increased during growth in
      an acidic environment due to induction of the acetoin pathway. Quantification of
      the relative contributions allowed us to construct a model for regulation of
      citrate utilization in L. lactis biovar diacetylactis. This knowledge will help
      to select conditions to improve flavour formation from citrate.

PMID- 29215193
TI  - Metabolomics of tomato xylem sap during bacterial wilt reveals Ralstonia
      solanacearum produces abundant putrescine, a metabolite that accelerates wilt
      disease.
AB  - Ralstonia solanacearum thrives in plant xylem vessels and causes bacterial wilt
      disease despite the low nutrient content of xylem sap. We found that R.
      solanacearum manipulates its host to increase nutrients in tomato xylem sap,
      enabling it to grow better in sap from infected plants than in sap from healthy
      plants. Untargeted GC/MS metabolomics identified 22 metabolites enriched in R.
      solanacearum-infected sap. Eight of these could serve as sole carbon or nitrogen
      sources for R. solanacearum. Putrescine, a polyamine that is not a sole carbon or
      nitrogen source for R. solanacearum, was enriched 76-fold to 37 uM in R.
      solanacearum-infected sap. R. solanacearum synthesized putrescine via a SpeC
      ornithine decarboxylase. A DeltaspeC mutant required >= 15 uM exogenous
      putrescine to grow and could not grow alone in xylem even when plants were
      treated with putrescine. However, co-inoculation with wildtype rescued DeltaspeC
      growth, indicating R. solanacearum produced and exported putrescine to xylem sap.
      Intriguingly, treating plants with putrescine before inoculation accelerated wilt
      symptom development and R. solanacearum growth and systemic spread. Xylem
      putrescine concentration was unchanged in putrescine-treated plants, so the
      exogenous putrescine likely accelerated disease indirectly by affecting host
      physiology. These results indicate that putrescine is a pathogen-produced
      virulence metabolite.

PMID- 29215195
TI  - Temporomandibular joint positional change accompanies post-surgical mandibular
      relapse-A long-term retrospective study among patients who underwent mandibular
      advancement.
AB  - OBJECTIVE: This study evaluated the relationship between follow-up
      temporomandibular joint positional change and mandibular stability among patients
      who had orthognathic and orthodontic treatment for a skeletal Class II
      malocclusion. METHODS: Thirty-seven patients who underwent 2-jaw surgery (Le Fort
      I osteotomy, bilateral sagittal split ramus osteotomy and genioplasty with rigid
      internal fixation) were included with an average follow-up length of 8.10 +/-
      2.06 years. They were categorized into a stable and unstable group according to
      follow-up mandibular change in the sagittal direction. Temporomandibular joint
      spaces were measured on serial magnetic resonance images, prior to orthodontic
      treatment (T0), upon completion of orthodontic treatment following surgery (T1),
      and at least 5 years post-completion of the treatment (T2). RESULTS: While the
      maxillary position was stable during the follow-up period, the mandibular
      positional change was statistically significant (the relapse amount was -0.81 +/-
      1.52 mm at B point). An increase in the anterior joint space and superior joint
      space was found to correlate with the follow-up mandibular backward movement.
      CONCLUSIONS: Patients who underwent orthognathic and orthodontic treatment to
      correct mandibular retrognathism displayed follow-up mandibular relapse in the
      sagittal direction. The relapse is accompanied by condylar positional change.

PMID- 29215197
TI  - Enrichment of gamma-aminobutyric acid in bean sprouts: Exploring biosynthesis of
      plant metabolite using common household reagents.
AB  - The enrichment of plant foods with gamma-aminobutyric acid (GABA) is currently an
      interesting issue in the field of nutraceuticals and can be used as an experiment
      for upper-division undergraduate students. Here, an interdisciplinary hands-on
      experiment to produce GABA-enriched mung bean sprouts using common household
      reagents is described. Based on the GABA biosynthesis pathways, two key factors,
      being the availability of l-glutamic acid and the acidification of the
      germination environment, were chosen for the study of the effects on the
      enhancement of GABA levels. The activities not only led students to a deeper
      understanding of biochemistry contents, but also gave the students the
      opportunity to work with experimental design, analytical chemistry, and
      statistical data analysis. Furthermore, since mung bean sprouts are familiar
      foods and the reagents used for germination are easily obtainable and generally
      recognized as safe, the optimal protocol investigated in the lab could be further
      applied to the production of bean sprouts with enhanced nutritional values in
      everyday life, promoting the transfer of knowledge learned in school to practical
      environments such as home and community. (c) 2017 by The International Union of
      Biochemistry and Molecular Biology, 46(2):155-161, 2018.

PMID- 29215196
TI  - Comparison between sodium-glucose cotransporter 2 inhibitors and pioglitazone as
      additions to insulin therapy in type 2 diabetes patients: A systematic review
      with an indirect comparison meta-analysis.
AB  - AIMS/INTRODUCTION: We aimed to evaluate the efficacy and safety of pioglitazone
      (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to
      insulin therapy for the management of type 2 diabetes mellitus. MATERIALS AND
      METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled
      Trials and ClinicalTrials.gov through December 2016. Randomized controlled trials
      published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus
      insulin (PIO/INS) with placebo plus insulin (PCB/INS) in type 2 diabetes mellitus
      patients were included. We compared the efficacy and safety between SGLT2i/INS
      and PIO/INS indirectly. RESULTS: A total of 14 randomized controlled trials
      comparing 7,226 participants were included (8 SGLT2i and 6 PIO studies).
      SGLT2i/INS achieved similar reductions in hemoglobin A1c (weighted mean
      difference [WMD] -0.01% [-0.1 mmol/mol], 95% confidence interval [CI] -0.25 to
      0.22% [-2.7 to -2.4 mmol/mol]; P = 0.896) and fasting plasma glucose (WMD -0.90
      mg/dL, 95% CI: -15.50 to 13.71 mg/dL; P = 0.904), and a similar proportion of
      participants achieved hemoglobin A1c <7.0% (<53.0 mmol/mol; relative risk 0.98,
      95% CI: 0.73 to 1.33; P = 0.917) as compared with the PIO/INS group, with greater
      weight reduction (WMD -4.54 kg, 95% CI: -5.67 to -3.41 kg; P < 0.001). PIO/INS
      showed non-significant trends toward a higher risk of hypoglycemia (relative risk
      1.15, 95% CI: 0.97 to 1.35; P = 0.102) and higher reduction of total daily
      insulin doses (WMD -2.45 IU/day, 95% CI: -7.30 to 2.40 IU/day; P = 0.438).
      CONCLUSIONS: Both PIO and SGLT2i are feasible adjunctive oral agents to pre
      existing insulin therapy in individuals with inadequately controlled type 2
      diabetes mellitus.

PMID- 29215198
TI  - Inflammatory signalling regulates eccentric contraction-induced protein synthesis
      in cachectic skeletal muscle.
AB  - BACKGROUND: Skeletal muscle responds to eccentric contractions (ECC) with an
      anabolic response that involves the induction of protein synthesis through the
      mechanistic target of rapamycin complex 1. While we have reported that repeated
      ECC bouts after cachexia initiation attenuated muscle mass loss and inflammatory
      signalling, cachectic muscle's capacity to induce protein synthesis in response
      to ECC has not been determined. Therefore, we examined cachectic muscle's ability
      to induce mechano-sensitive pathways and protein synthesis in response to an
      anabolic stimulus involving ECC and determined the role of muscle signal
      transducer and activator of transcription 3 (STAT3)/nuclear factor kappa-light
      chain-enhancer of activated B cells (NFkappaB) signalling on ECC-induced anabolic
      signalling. METHODS: Mechano-sensitive pathways and anabolic signalling were
      examined immediately post or 3 h after a single ECC bout in cachectic male
      ApcMin/+ mice (n = 17; 16 +/- 1% body weight loss). Muscle STAT3/NFkappaB
      regulation of basal and ECC-induced anabolic signalling was also examined in an
      additional cohort of ApcMin/+ mice (n = 10; 16 +/- 1% body weight loss) that
      received pyrrolidine dithiocarbamate 24 h prior to a single ECC bout. In all
      experiments, the left tibialis anterior performed ECC while the right tibialis
      anterior served as intra-animal control. Data were analysed by Student's t-test
      or two-way repeated measures analysis of variance with Student-Newman-Keuls post
      hoc when appropriate. The accepted level of significance was set at P < 0.05 for
      all analysis. RESULTS: ApcMin/+ mice exhibited a cachectic muscle signature
      demonstrated by perturbed proteostasis (Ribosomal Protein S6 (RPS6), P70S6K,
      Atrogin-1, and Muscle RING-finger protein-1 (MuRF1)), metabolic (adenosine
      monophosphate-activated protein kinase, Peroxisome proliferator-activated
      receptor gamma coactivator 1-alpha (PGC-1alpha), and Cytochrome c oxidase subunit
      IV (COXIV)), and inflammatory (STAT3, NFkappaB, extracellular signal-regulated
      kinases 1 and 2, and P38) signalling pathway regulation. Nonetheless, mechano
      sensitive signalling pathways (P38, extracellular signal-regulated kinases 1 and
      2, and Protein kinase B (AKT)) were activated immediately post-ECC irrespective
      of cachexia. While cachexia did not attenuate ECC-induced P70S6K activation, the
      protein synthesis induction remained suppressed compared with healthy controls.
      However, muscle STAT3/NFkappaB inhibition increased basal and ECC-induced protein
      synthesis in cachectic ApcMin/+ mice. CONCLUSIONS: These studies demonstrate that
      mechano-sensitive signalling is maintained in cachectic skeletal muscle, but
      chronic STAT3/NFkappaB signalling serves to attenuate basal and ECC-induced
      protein synthesis.

PMID- 29215199
TI  - Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced
      Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine
      Production.
AB  - Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number
      of bioactive factors, including neurotrophic growth factors, capable of
      supporting and improving nerve regeneration. However, with a finite culture
      expansion capacity, MSCs are inherently limited in their lifespan and use. We
      examined here the potential utility of an alternative, mesenchymal-like cell
      source, derived from induced pluripotent stem cells, termed induced mesenchymal
      progenitor cells (MiMPCs). We found that several genes were upregulated and
      proteins were produced in MiMPCs that matched those previously reported for MSCs.
      Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors,
      including brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6),
      leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted
      neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared
      with control cultures. Cotreatment with a pharmacological Trk-receptor inhibitor
      did not result in significant decrease in MiMPC-induced neurite outgrowth, which
      was however inhibited upon Jak/STAT3 blockade. These findings suggest that the
      MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on
      BDNF, but instead Jak/STAT3 activation by IL-6 and/or LIF is likely to be
      critical neurotrophic signaling pathways of the MiMPC secretome. Taken together,
      these findings suggest MiMPCs as a renewable, candidate source of therapeutic
      cells and a potential alternative to MSCs for peripheral nerve repair, in view of
      their ability to promote nerve growth by producing many of the same growth
      factors and cytokines as Schwann cells and signaling through critical
      neurotrophic pathways. Stem Cells Translational Medicine 2018;7:45-58.

PMID- 29215202
TI  - Context-dependent vertical transmission shapes strong endosymbiont community
      structure in the pea aphid, Acyrthosiphon pisum.
AB  - Animal-associated microbiomes are often comprised of structured, multispecies
      communities, with particular microbes showing trends of co-occurrence or
      exclusion. Such structure suggests variable community stability, or variable
      costs and benefits-possibilities with implications for symbiont-driven host
      adaptation. In this study, we performed systematic screening for maternally
      transmitted, facultative endosymbionts of the pea aphid, Acyrthosiphon pisum.
      Sampling across six locales, with up to 5 years of collection in each, netted
      significant and consistent trends of community structure. Co-infections between
      Serratia symbiotica and Rickettsiella viridis were more common than expected,
      while Rickettsia and X-type symbionts colonized aphids with Hamiltonella defensa
      more often than expected. Spiroplasma co-infected with other endosymbionts quite
      rarely, showing tendencies to colonize as a single species monoculture. Field
      estimates of maternal transmission rates help to explain our findings: while
      Serratia and Rickettsiella improved each other's transmission, Spiroplasma
      reduced transmission rates of co-infecting endosymbionts. In summary, our
      findings show that North American pea aphids harbour recurring combinations of
      facultative endosymbionts. Common symbiont partners play distinct roles in pea
      aphid biology, suggesting the creation of "generalist" aphids receiving symbiont
      based defence against multiple ecological stressors. Multimodal selection, at the
      host level, may thus partially explain our results. But more conclusively, our
      findings show that within-host microbe interactions, and their resulting impacts
      on transmission rates, are an important determinant of community structure.
      Widespread distributions of heritable symbionts across plants and invertebrates
      hint at the far-reaching implications for these findings, and our work further
      shows the benefits of symbiosis research within a natural context.

PMID- 29215203
TI  - Analysis of ketamine and xylazine in complex matrices using two-dimensional
      liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Analyzing tissue samples is routinely performed when liquid biological
      samples are not available for replicate analysis. Preparing complex matrices,
      such as tissue, for analysis can be time-consuming. Traditional sample
      preparation methods typically begin with homogenization followed by a sample
      clean-up step such as liquid-liquid or solid-phase extraction. Samples are
      typically eluted, evaporated and reconstituted prior to instrumental analysis.
      The aim of this project was to evaluate the utility of multi-dimensional
      chromatography in reducing the amount of time from sample acquisition to
      analysis. METHODS: Tissue specimens were homogenized using a ceramic beads
      shaker. Homogenates were then diluted and loaded onto a mixed mode solid-phase
      sorbent. The sorbent was washed, and the final eluate was transferred directly to
      vials without evaporation or reconstitution steps. Analysis was performed using a
      two-dimensional (2D) ultra-performance liquid chromatography (UPLC) configuration
      with an At-column dilution option coupled to a triple quadrupole mass
      spectrometer. The target analytes (xylazine and ketamine) were quantified under
      multiple reaction monitoring (MRM) using electrospray ionization (ESI) in
      positive mode. RESULTS: The lowest limit of detection evaluated in this study was
      0.01 ng/mL. The linear dynamic range utilized was 0.1 to 10 ng/mL. The
      concentrations for xylazine in their respective tissues ranged from 0 to 0.316
      ng/mL. Ketamine concentrations ranged from 0 to 0.905 ng/mL. The overall time for
      sample preparation was reduced to 30 min. The total run time was 10 min.
      CONCLUSIONS: The use of multidimensional chromatography with At-column-dilution
      allows for significant reduction in sample preparation time. The concentrations
      determined in these samples highlight the need for sensitive analytical
      techniques with the ability to detect analyte concentrations at sub ng/mL.

PMID- 29215200
TI  - miR-424-5p reduces ribosomal RNA and protein synthesis in muscle wasting.
AB  - BACKGROUND: A loss of muscle mass occurs as a consequence of a range of chronic
      and acute diseases as well as in older age. This wasting results from an
      imbalance of protein synthesis and degradation with a reduction in synthesis and
      resistance to anabolic stimulation often reported features. Ribosomes are
      required for protein synthesis, so changes in the control of ribosome synthesis
      are potential contributors to muscle wasting. MicroRNAs (miRNAs) are known
      regulators of muscle phenotype and have been shown to modulate components of the
      protein synthetic pathway. One miRNA that is predicted to target a number of
      components of protein synthetic pathway is miR-424-5p, which is elevated in the
      quadriceps of patients with chronic obstructive pulmonary disease (COPD).
      METHODS: Targets of miR-424-5p were identified by Argonaute2 pull down, and the
      effects of the miRNA on RNA and protein expression were determined by
      quantitative polymerase chain reaction and western blotting in muscle cells in
      vitro. Protein synthesis was determined by puromycin incorporation in vitro. The
      miRNA was over-expressed in the tibialis anterior muscle of mice by
      electroporation and the effects quantified. Finally, quadriceps expression of the
      miRNA was determined by quantitative polymerase chain reaction in patients with
      COPD and intensive care unit (ICU)-acquired weakness and in patients undergoing
      aortic surgery as well as in individuals from the Hertfordshire Sarcopenia Study.
      RESULTS: Pull-down assays showed that miR-424-5p bound to messenger RNAs encoding
      proteins associated with muscle protein synthesis. The most highly enriched
      messenger RNAs encoded proteins required for the Pol I RNA pre-initiation complex
      required for ribosomal RNA (rRNA) transcription, (PolR1A and upstream binding
      transcription factor). In vitro, miR-424-5p reduced the expression of these RNAs,
      reduced rRNA levels, and inhibited protein synthesis. In mice, over-expression of
      miR-322 (rodent miR-424 orthologue) caused fibre atrophy and reduced upstream
      binding transcription factor expression and rRNA levels. In humans, elevated miR
      424-5p associated with markers of disease severity in COPD (FEV1 %), in patients
      undergoing aortic surgery (LVEF%), and in patients with ICU-acquired weakness
      (days in ICU). In patients undergoing aortic surgery, preoperative miR-424-5p
      expression in skeletal muscle was associated with muscle loss over the following
      7 days. CONCLUSIONS: These data suggest that miR-424-5p regulates rRNA synthesis
      by inhibiting Pol I pre-initiation complex formation. Increased miR-424-5p
      expression in patients with conditions associated with muscle wasting is likely
      to contribute to the inhibition of protein synthesis and loss of muscle mass.

PMID- 29215204
TI  - Titanium Fiber Plates for Bone Tissue Repair.
AB  - Titanium plates are widely used in clinical settings because of their high bone
      affinity. However, owing to their high elastic modulus, these plates are not
      suitable for bone repair since their proximity to the bone surface for prolonged
      periods can cause stress shielding, leading to bone embrittlement. In contrast,
      titanium fiber plates prepared by molding titanium fibers into plates by
      simultaneously applying compression and shear stress at normal room temperature
      can have an elastic modulus similar to that of bone cortex, and stress shielding
      will not occur even when the plate lies flush against the bone's surface.
      Titanium fibers can form a porous structure suitable for cell adhesion and as a
      bone repair scaffold. A titanium fiber plate is combined with osteoblasts and
      shown that the titanium fiber plate is better able to facilitate bone tissue
      repair than the conventional titanium plate when implanted in rat bone defects.
      Capable of being used in close contact with bone for a long time, and even
      capable of promoting bone repair, titanium fiber plates have a wide range of
      applications, and are expected to make great contributions to clinical management
      of increasing bone diseases, including bone fracture repair and bone regenerative
      medicine.

PMID- 29215205
TI  - Bioinspired Flexible and Tough Layered Peptide Crystals.
AB  - One major challenge of functional material fabrication is combining flexibility,
      strength, and toughness. In several biological and artificial systems, these
      desired mechanical properties are achieved by hierarchical architectures and
      various forms of anisotropy, as found in bones and nacre. Here, it is reported
      that crystals of N-capped diphenylalanine, one of the most studied self
      assembling systems in nanotechnology, exhibit well-ordered packing and
      diffraction of sub-A resolution, yet display an exceptionally flexible nature. To
      explore this flexibility, the mechanical properties of individual crystals are
      evaluated, assisted by density functional theory calculations. High-resolution
      scanning electron microscopy reveals that the crystals are composed of layered
      self-assembled structures. The observed combination of strength, toughness, and
      flexibility can therefore be explained in terms of weak interactions between
      rigid layers. These crystals represent a novel class of self-assembled layered
      materials, which can be utilized for various technological applications, where a
      combination of usually contradictory mechanical properties is desired.

PMID- 29215206
TI  - Once frail, always frail? Frailty transitions in home care users with
      intellectual and developmental disabilities.
AB  - AIM: Frailty is understood as a dynamic non-linear process, and used to indicate
      age-related decline. Recent work has shown that adults with intellectual and
      developmental disabilities experience higher rates of frailty at much earlier
      ages than the general population. The present study describes transitions in
      frailty status (i.e. non-frail, pre-frail, frail) over 1 year, and explores the
      association between baseline frailty status and worsening/death over time.
      METHODS: Results are based on secondary analysis of 2893 individuals with
      intellectual and developmental disabilities receiving community-based home care
      services in Ontario (Canada). Frailty status is based on a validated 42-item
      frailty index (FI); where FI <=0.21 indicates non-frail, 0.21 < FI <= 0.3
      indicates pre-frail and FI >0.30 indicates frail. Baseline characteristics of
      frailty groups at baseline were compared using the chi2 -test/analysis of
      variance. Relative risk of worsening/dying was calculated using a modified
      Poisson regression model. RESULTS: Initially, 67.0% of participants were non
      frail, 16.2% were pre-frail and 16.8% were frail. Of those non-frail at baseline,
      84.3% remained non-frail, 11.8% worsened and 3.9% died. Among those initially pre
      frail, 37.0% remained stable, 35.3% improved, 18.2% worsened and 9.6% died.
      Although similar proportions of frail individuals improved (37.4%) or remained
      stable (36.8%), 25.9% had died. After controlling for other factors, being pre
      frail at baseline was associated with an increase in the risk of worsening or
      death (RR 1.24, 95% CI 1.04-1.49). CONCLUSIONS: While many experience worsening
      of frailty status, stability and improvement are viable goals of care. Future
      research should examine the rate at which non-frail, pre-frail and frail
      individuals accumulate deficits, as well as the impact of home care services on
      frailty. Geriatr Gerontol Int 2018; 18: 547-553.

PMID- 29215207
TI  - Integration of Plasmonic Effects and Schottky Junctions into Metal-Organic
      Framework Composites: Steering Charge Flow for Enhanced Visible-Light
      Photocatalysis.
AB  - A wide range of light absorption and rapid electron-hole separation are desired
      for efficient photocatalysis. Herein, on the basis of a semiconductor-like metal
      organic framework (MOF), a Pt@MOF/Au catalyst with two types of metal-MOF
      interfaces integrates the surface plasmon resonance excitation of Au nanorods
      with a Pt-MOF Schottky junction, which not only extends the light absorption of
      the MOF from the UV to the visible region but also greatly accelerates charge
      transfer. The spatial separation of Pt and Au particles by the MOF further steers
      the formation of charge flow and expedites the charge migration. As a result, the
      Pt@MOF/Au presents an exceptionally high photocatalytic H2 production rate by
      water splitting under visible light irradiation, far superior to Pt/MOF/Au,
      MOF/Au and other counterparts with similar Pt or Au contents, highlighting the
      important role of each component and the Pt location in the catalyst.

PMID- 29215208
TI  - Image-guided recording system for spatial and temporal mapping of neuronal
      activities in brain slice.
AB  - In this study, we introduce the novel image-guided recording system (IGRS) for
      efficient interpretation of neuronal activities in the brain slice. IGRS is
      designed to combine microelectrode array (MEA) and optical coherence tomography
      at the customized upright microscope. It allows to record multi-site neuronal
      signals and image of the volumetric brain anatomy in a single body configuration.
      For convenient interconnection between a brain image and neuronal signals, we
      developed the automatic mapping protocol that enables us to project acquired
      neuronal signals on a brain image. To evaluate the performance of IGRS,
      hippocampal signals of the brain slice were monitored, and corresponding with two
      dimensional neuronal maps were successfully reconstructed. Our results indicated
      that IGRS and mapping protocol can provide the intuitive information regarding
      long-term and multi-sites neuronal signals. In particular, the temporal and
      spatial mapping capability of neuronal signals would be a very promising tool to
      observe and analyze the massive neuronal activity and connectivity in MEA-based
      electrophysiological studies.

PMID- 29215209
TI  - Letter from Japan.

PMID- 29215210
TI  - A Comparative Transcriptomics Workflow for Analyzing Microarray Data From CHO
      Cell Cultures.
AB  - Microarray-based comparative transcriptomics analysis is a powerful tool to
      understand therapeutic protein producing mammalian cell lines at the gene
      expression level. However, an integrated analysis workflow specifically designed
      for end-to-end analysis of microarray data for CHO cells, the most prevalent host
      for commercial recombinant protein production, is lacking. To address this gap,
      an automated data analysis workflow in R that leverages public domain analysis
      modules is developed to analyze microarray based gene expression data. In
      addition to testing the global transcriptome differences of CHO cells at
      different conditions, the workflow identifies differentially expressed genes and
      pathways with intuitive visualizations as the outputs. The utility of this
      automated workflow is demonstrated by comparing the transcriptomic profiles of
      recombinant protein expressing CHO cells with and without a temperature shift.
      Statistically significant differential expression at the gene, pathway, and
      global transcriptome levels are identified and visualized. An automated workflow
      like the one developed in this study will enable rapid translation of CHO culture
      microarray data into biologically relevant information for mechanism-driven cell
      line optimization and bioprocess development.

PMID- 29215211
TI  - A study of hormonal effects in cervical smear samples using Raman spectroscopy.
AB  - Raman spectroscopy is a powerful tool that has the potential to be used as a
      screening method for cervical cancer. It is a label-free, low-cost method
      providing a biochemical fingerprint of a given sample. The objective of this
      study was to address patient-to-patient variability contributed by hormonal
      effects due to the menstrual cycle, the use of hormone-based contraceptives (HC)
      and the onset of menopause, and to determine if these changes would affect the
      ability to successfully identify dyskaryotic cells. Raman spectra were recorded
      from unstained ThinPrep cervical samples (45 cytology negative and 15 high-grade
      dyskaryosis (high-grade squamous intraepithelial lesion, HSIL) samples using a
      HORIBA Jobin Yvon XploRA system. HPV DNA testing was also performed. Clinical
      data collected included date of the last menstrual period, the use of HC and/or
      menopausal status. Spectral changes were observed depending on the day of the
      menstrual cycle and on the use of HC. Despite this, HSIL could be discriminated
      from normal cells regardless of the day on which the sample was taken or the use
      of HC.

PMID- 29215212
TI  - Enhancement of methane production from 1-hexadecene by additional electron
      donors.
AB  - 1-Hexadecene-contaminated wastewater is produced in oil refineries and can be
      treated in methanogenic bioreactors, although generally at low conversion rates.
      In this study, a microbial culture able to degrade 1-hexadecene was enriched, and
      different stimulation strategies were tested for enhancing 1-hexadecene
      conversion to methane. Seven and three times faster methane production was
      obtained in cultures stimulated with yeast extract or lactate, respectively,
      while cultures amended with crotonate lost the ability to degrade 1-hexadecene.
      Methane production from 1-hexadecene was not enhanced by the addition of extra
      hydrogenotrophic methanogens. Bacteria closely related to Syntrophus and
      Smithella were detected in 1-hexadecene-degrading cultures, but not in the ones
      amended with crotonate, which suggests the involvement of these bacteria in 1
      hexadecene degradation. Genes coding for alkylsuccinate synthase alpha-subunit
      were detected in cultures degrading 1-hexadecene, indicating that hydrocarbon
      activation may occur by fumarate addition. These findings are novel and show that
      methane production from 1-hexadecene is improved by the addition of yeast extract
      or lactate. These extra electron donors may be considered as a potential
      bioremediation strategy of oil-contaminated sites with bioenergy generation
      through methane production.

PMID- 29215213
TI  - Identifying protist consumers of photosynthetic picoeukaryotes in the surface
      ocean using stable isotope probing.
AB  - Photosynthetic picoeukaryotes contribute a significant fraction of primary
      production in the upper ocean. Micromonas pusilla is an ecologically relevant
      photosynthetic picoeukaryote, abundantly and widely distributed in marine waters.
      Grazing by protists may control the abundance of picoeukaryotes such as M.
      pusilla, but the diversity of the responsible grazers is poorly understood. To
      identify protists consuming photosynthetic picoeukaryotes in a productive North
      Pacific Ocean region, we amended seawater with living 15 N, 13 C-labelled M.
      pusilla cells in a 24-h replicated bottle experiment. DNA stable isotope probing,
      combined with high-throughput sequencing of V4 hypervariable regions from 18S
      rRNA gene amplicons (Tag-SIP), identified 19 operational taxonomic units (OTUs)
      of microbial eukaryotes that consumed M. pusilla. These OTUs were distantly
      related to cultured taxa within the dinoflagellates, ciliates, stramenopiles
      (MAST-1C and MAST-3 clades) and Telonema flagellates, thus, far known only from
      their environmental 18S rRNA gene sequences. Our discovery of eukaryotic prey
      consumption by MAST cells confirms that their trophic role in marine microbial
      food webs includes grazing upon picoeukaryotes. Our study provides new
      experimental evidence directly linking the genetic identity of diverse
      uncultivated microbial eukaryotes to the consumption of picoeukaryotic
      phytoplankton in the upper ocean.

PMID- 29215214
TI  - Tiotropium in Early-Stage COPD.

PMID- 29215215
TI  - Tiotropium in Early-Stage COPD.

PMID- 29215216
TI  - Tiotropium in Early-Stage COPD.

PMID- 29215217
TI  - Food Allergy.

PMID- 29215218
TI  - Use of Liver Imaging and Biopsy in Clinical Practice.

PMID- 29215219
TI  - Use of Liver Imaging and Biopsy in Clinical Practice.

PMID- 29215220
TI  - Use of Liver Imaging and Biopsy in Clinical Practice.

PMID- 29215221
TI  - Thrombophilia Testing and Venous Thrombosis.

PMID- 29215222
TI  - [PARASITES FAUNA OF THE LAKE KRONOTSKOE CHARRS (SALVELINUS), KAMCHATKA].
AB  - The new data on the parasites fauna of the Lake Kronotskoe sympatric charr forms
      (genusSalvelinus (Nilsson) Richardson, 1836) is presented. Parasites fauna of
      Bigmouth andSmallmouth charr forms are described for the first time. The
      information about Longheadcharr, Nosed charr and White charr parasites is added.
      29 species of parasites from 9 classeswere found: Oligohymenophorea, Myxosporea,
      Monogenea, Trematoda, Cestoda, Nematoda,Acantocephala, Crustacea and Hirudinea.
      Longhead charr was the most intensivelyinfected by Proteocephalus longicollis
      (Zeder, 1800) (abundance 306.0) and Neoechinorhynchussalmonis Ching, 1984
      (abundance 230.0). White charr was mostly infected byCrepidostomum Braun, 1900
      (abundance 242.2) and P. longicollis (abundance 183.4). Nosedcharr group that
      feed on gammarids was infected mostly by Crepidostomum spp.(abundance 3461.3),
      Cyathocephalus truncatus (Pallas, 1781) (abundance 179.9) and Cystidicolafarionis
      Fisher, 1798 (abundance 169.0); while Chironomidae consumers groupwas infected
      mostly by Diplostomum Nordmann, 1832 (abundance 62.3) and Phyllodistomumumblae
      (Fabricius, 1780) (abundance 27.3). Bigmouth charr was infected mostly byP.
      longicollis (abundance 17.0) and Eubolhrium salvelini Schrank, 1790 (abundance
      11.0),Smallmouth charr form - by P. longicollis (abundance 67.0) and Diplostomum
      sp. (abundance64.2). Sympatric flock of charrs form the Lake Kronotskoe
      (Kamchatka) is the mostpolymorphic for the genus Salvelinus in Eurasia. According
      to the parasitological analysisthis flock consists six ecological forms.

PMID- 29215223
TI  - [FIRST RECORD OF RHADINORHYNCHUS COLOLABIS (ACANTHOCEPHALA: RHADINORHYNCHIDAE)
      FROM THE CHERRY SALMON IN THE SEA OF JAPAN].
AB  - Drawing, description and characteristics of Rhadinorhynchus cololabis, registered
      forthe first time from Oncorhynchus masou in the Sea of Japan (northern part of
      PrimoryeTerritory) are given. Ten species of acanthocephalans from the cherry
      salmon in the PrimorskyTerritory were recorded.

PMID- 29215224
TI  - Magnified Bacteria Powerful Motivator for Hand Hygiene Compliance.
AB  - Infection prevention specialists at Henry Ford Hospital in Detroit have found
      that showing healthcare workers magnified pictures of bacteria found ontheir
      hands and in their surrounding units can be a powerful motivator for improved
      hand hygiene compliance. When tested in four units during a one-month period, the
      intervention boosted hand hygiene compliance by an average of 24%. Investigators
      note that to be successful, the intervention must be paired with an effective
      compliance monitoring program. For the study, investigators visited each unit
      twice per week, during which they would swab various items as well as employees'
      hands using and adenosine triphosphate (ATP) meter, a hand-held device that
      measures living organisms. During each unit visit, infection prevention
      specialists would show unit personnel pictures from a compilation of 12 magnified
      images of bacteria that had been lifted from the unit. This was to demonstrate
      what the bacteria would look like under a microscope. The unsavory pictures
      produced immediate increases in had hygiene compliance, and prompted healthcare
      workers to see who could produce the best ATP meter readings on subsequent
      infection prevention specialist visits.

PMID- 29215225
TI  - [THE SYSTEM OF XENOBIOTICS BIOTRANSFORMATION OF HELMINTHS. RESEMBLANCE AND
      DIFFERENSES FROM SIMILAR HOST SYSTEMS (REWEW)].
AB  - The three phases system xenobiotic biotransformation in cells as prokaryotes as
      eukaryoteswas formed during the process of evolution. Clear and managed function
      of all threelinks of this system guarantee the survival of living organisms at
      alteration of chemicalcomponent of environment. Oxidation, reduction or
      hydrolysis of xenobiotics realize inphase I by insertion or opening reactive and
      hydrophilic groups in structure of drug molecule.In phase II xenobiotics or their
      metabolites from phase I conjugate with endogeniccompounds, main of there are
      glutathione, glucuronic acid, amino acids and sulphates.Active transport of
      substrata, metabolites and conjugates through cell lipid membranesspecial
      transport proteins carry out (phase III).The system of xenobiotics
      biotransformation of helminths has essential differencesfrom the same of
      vertebrate hosts. In particular, parasites do not reveal the activity of
      primeoxidases of phase I, such as CYP or FMO, in spite of the genes of these
      enzymes inDNA. As this phenomenon displays mainly in adult helminths, living in
      guts of vertebrates,then the hypothesis was formulated that this effect is
      related with adaptation to conditionsof strong deficiency of oxygen, arise in a
      process of evolution (Kotze et al., 2006).Literature data testify the existence
      in helminths of unique forms of enzymes of phaseII, the investigation of which
      present doubtless interest in relation with possible role inadaptation to
      parasitic mode of life. Notwithstanding that many of helminths GST in greateror
      lesser degree similar with enzymes of M, P, S and O classes of other organisms,
      neverthelessthey have essential structural differences as compared with enzymes
      of hoststhat makes perspective the search of specific anthelminthics
      vaccines.Transport of xenobiotics is now considered phase III of
      biotransformation. It wasshown that proteins of this phase (ATP binding cassette
      transporters (ABC ) of parasites)play a key role in efflux of lipophilic
      xenobiotics, hydrophilic metabolites and conjugatesand take part in forming of
      anthelminthics resistance. Some of these transporters, such asP-glycoprotein
      (Pgp), are important for drug resistance of helminths. In particular, a
      correlationbetween the level of expression of Pgp and resistance of S. mansoni
      and F. hepaticato widely used anthelminthics as praziquantel and triclabendazol
      exist.

PMID- 29215226
TI  - [HOST SPECIFICITY IN MICROSPORIDIA].

PMID- 29215227
TI  - [FLEAS (SIPHONAPTERA) OF MAMMALS AND BIRDS IN THE CISCAUCASIA].
AB  - Flea fauna of Ciscaucasia is represented by 76 species, 13 of which are
      associated withbirds and all the other with mammals. Rodent parasites are most
      numerous; fleas associatedwith predators, bats and insectivora are less abundant.
      Fleas parasitize on different speciesof birds of the orders Passeriformes,
      Anseriformes, Falconiformes, and Strigiformes.Among 41 flea genera known from the
      Caucasus, species of the genera Amalaraeus, Araeopsylla,Atyphloceras,
      Caenopsylla, Callopsvlla, Doratopsvlla, Paraneopsvlla,
      Peromyscopsylla,Phaenopsylla, Tarsopsylla, and Wagnerina are absent in the
      Ciscaucasia. Onlytwo subendemic species were revealed in this area. Thirty three
      flea species are distributedover the entire territory; the distribution of other
      species is limited to landscapes of one ortwo natural areas.

PMID- 29215228
TI  - The Impact of an HSA-Eligible Health Plan on Health Care Services Use and
      Spending by Worker Income.

PMID- 29215229
TI  - [EXPERIENCE IN THE APPLICATION OF DATABASES ON BLOODSUCKING INSECTS IN ZOOLOGICAL
      STUDIES].
AB  - The paper summarizes long-term experience of accumulating and summarizing
      thefaunistic information by means of separate databases (DB) and information
      analyticalsystems (IAS), and also prospects of its representation by modern multi
      user informationalsystems. The experience obtained during development and
      practical use of thePARHOST1 IAS for the study of the world flea fauna and work
      with personal databasescreated for the study of bloodsucking insects (lice and
      blackflies) is analyzed. Researchcollection material on type series of 57 species
      and subspecies of fleas of the fauna of Russiawas approved as a part of multi
      user information retrieval system on the web-portal ofthe Zoological Institute of
      the Russian Academy of Sciences. According former investigations,the system
      allows depositing the information in the authentic form and performingits gradual
      transformation, i. e. its unification and structuring. In order to provide
      continuityof DB refill, the possibility of work of operators with different
      degree of competenceis provided.

PMID- 29215230
TI  - What Does Consistent Participation in 401(k) Plans Generate? Changes in 401(k)
      Plan Account Balances, 2010-2014.

PMID- 29215231
TI  - Health Savings Account Balances, Contributions, Distributions, and Other Vital
      Statistics, 2015: Estimates from the EBRI HSA Database.

PMID- 29215232
TI  - Narrow Provider Networks for Employer Plans.

PMID- 29215233
TI  - Individual Retirement Account Balances, Contributions, Withdrawals, and Asset
      Allocation Longitudinal Results 2010-2014: The EBRI IRA Database.

PMID- 29215234
TI  - How Does the Level of Household Savings Affect Preference for Immediate
      Annuities?

PMID- 29215235
TI  - The 2017 Retirement Confidence Survey: Many Workers Lack Retirement Confidence
      and Feel Stressed About Retirement Preparations.

PMID- 29215236
TI  - [Effect of intranasally administered glutamate antibodies on the content of
      excitatory and inhibitory amino acids in the rat's hippocampus and hypothalamus
      at the combined stress exposure].
AB  - Objective. We studied the effect of glutamate antibodies by intranasal
      administration on the development of stress reactions and aspartate, glycine and
      taurine content in the brain structures of rats with different initial behavioral
      activity (active and passive). Methods. Stress caused by placing the animals in
      the living cell with water (21 degrees S) covered with a grid for 30 min.
      Glutamate antibodies in a dose of 250 mg/kg in a volume of 10 mkl were
      administered intranasally to the experimental group of rats immediately after the
      stress. After 1 h after stress exposure and antibodies administration in all rats
      was investigated motor activity in the test of the "open field". Amino acids
      aspartate, glycine and taurine in the brain structures (hippocampus and
      hypothalamus) were determined by HPLC with fluorescence detection. Results.
      Combined water-immersion stress caused significant changes in the behavioral
      activity of rats in the "open field", but a more pronounced decline in the total
      index were observed in the behaviorally passive group of rats. The stress was
      accompanied by a change in the content of neurotransmitter amino acids (glycine
      and taurine) in the hippocampus. The most significant changes in the levels of
      glycine (decrease) and taurine (an increase) was observed in the hippocampus
      behaviorally active rats. Glutamate antibodies at a dose of 250 mg/kg
      administered intranasally immediately after stress exposure prevents the
      development of behavioral stress reactions and contributed to an increase in the
      hippocampus the content of glycine and taurine, related to stress-limiting
      systems. Conclusions. The glutamate antibodies under stress act as endogenous
      bioregulators and prevent the development of stress reactions.

PMID- 29215237
TI  - [Age-related changes of the latent period of simple sensorimotor reaction to the
      light stimuli in both men and women with different body mass index].
AB  - The study of the relationship of the latent period of simple sensorimotor
      reaction to the light stimulus and body mass index (BMI) in males and females
      aged 30-60 years (n = 507) was done. The boundary between the low (below Me -
      1SD) and middle (from Me - 1SD to Me + 1SD) BMI was the value of 22.74 kg/m2, the
      boundary between the middle and high (above Me + 1SD) BMI - 33.16kg/m2. It is
      shown thatthere isan increase inthe proportion of people with high BMI with age
      (faster and more pronounced - in women). Sensorimotor reaction latency to the
      light stimuli does not change in men, and declines with agein women. However the
      data obtained indicate that developed with age alimentary obesity does not
      adversely affect neurophysiological parameters of the sensorimotor reactivity.

PMID- 29215238
TI  - [Chronic ischemia of the brain: state structurally functional properties of
      erythrocytes ].
AB  - At patients with a chronic ischemia of a brain against an idiopathic hypertensia
      of the II stage development intra erythrocyte "an oxidative stress", depression
      of sorption ability of erythrocytes, change in a membrane of cells of a ratio of
      fractions of lipids due to decrease of the maintenance of glitserophospholipid
      and a sphingomyelin, augmentation of a lizophosphatidilkholin, cholesterol is
      taped. Change of presentability of the membranous proteins responsible for
      structurization and stabilization of a membrane of erythrocytes, a shaping,
      flexibility of a membrane and an intracellular metabolism is established. The
      important role of erythrocytes at a chronic ischemia of a brain based on the
      concept of their participation in a chain of the adaptive mechanisms supporting a
      homeostasis is noted.

PMID- 29215239
TI  - Health Plan Switching: A Case Study--Implications for Private- and Public-Health
      Insurance Exchanges and Increased Health Plan Choice.

PMID- 29215240
TI  - [Hemoglobin oxygen transport capacity in surgical endotoxicosis ].
AB  - In surgical endointoxication hemoglobin oxygen transport capacity of red blood
      cells (hemoglobin affinity ligands: the ability to bind and release ligands) is
      reduced and is associated with the severity of endogenous intoxication. Violation
      of oxygen transport function of hemoglobin at endogenous intoxication is
      associated with conformational changes of a biomolecule, and its possible
      influence on reactive oxygen species, which confirmed in experiments in vitro:
      under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates.
      Largely similar structural and functional changes in hemoglobin occur in patients
      with surgical endotoxicosis.

PMID- 29215241
TI  - [Chronic exposure to cold is adaptation without stress ].
AB  - It has been established that prolonged continuous cold exposure (+4 degrees C for
      24 hours/day, four weeks) causes an increase in brown fat weight, hypertrophy of
      the adrenal gland, spleen and did not affect cortisol and corticosterone levels
      in the blood serum in rats. Gastric ulcers were not observed in the rats. Chronic
      intermittent exposure to cold (+4 degrees C, 8 hours/day, 4 weeks) promoted an
      increase in the weight of brown fat, spleen, kidneys and heart, stomach ulcers
      and an alteration of cortisol and corticosterone levels were did observed. Short
      term intermittent exposure to cold (+4 degrees C, 1.5 hours/day, 4 weeks) did not
      affect the weight of brown fat, but promoted an increases in the weight of body,
      spleen, kidneys and heart, stomach ulcers were not found, cortisol and
      corticosterone levels was not changed.

PMID- 29215243
TI  - My Curtain Call: An inside look at a hospital stay for chest pain.

PMID- 29215242
TI  - [Expression of vascular endothelial growth factor (VEGF) in uterine tissues as
      one of the mechanisms of algogenezis in adenomyosis, associated with chronic
      pelvic pain].
AB  - Methods. For morphological studies it were using fragments of walls 60 uterus,
      received after hysterectomy in patients with pelvic pain on a background of
      diffuse adenomyosis II-III degree, and 30 uterus of women with painless form of
      adenomyosis. Expression of vascular endothelial growth factor (VEGF) was measured
      in endometrial and myometrial tissues using immunohistochemistry. The results
      showed a significantly higher expression of VEGF in patients with adenomyosis
      pain phenotype compared to the same in women with silent form in the epithelial
      cells of ectopic endometrium (14,7 +/- 1,6 vs. 10,7 +/- 1,6%, p<0,01) in the
      smooth muscle cells of the myometrium (12,6 +/- 1,4 vs. 9,6 +/- 1,2%, p<0,01), in
      the stromal cells of the myometrium (10,1 +/- 1,9 vs. 7,4 +/- 1,8%, p <0,01).

PMID- 29215244
TI  - [Hypolipidemic activity of N-cholinergic antagonist Benzohexonium in the
      experiments ].
AB  - Methods: Experiments were carried out on outbred albino male rats (n = 150, 230
      250 g). For modeling dislipoproteinemia (DLP) we used 3 models: single
      intraperitoneal injection of the detergent triton WR-1339; administration of
      ethanol; maintenance on a special hypercholesterolaemic diet (HD) during 21 days.
      Animals were divided into four groups: normal control, model group, gemfibrozil
      (Gfb) group, benzohexonium (Benz) group. Rats received per os benzohexonium
      (20mg/kg), reference drug gemfibrozil (50 mg/kg). We determined content of total
      cholesterol (TCh), triglycerides (TG) in samples of blood serum and liver, TCh in
      aorta. TCh, TG and Ch-HDL were analyzed spectrophotometrically using of
      standardized methods. Results: Compared with model group the contents of TCh, TG
      in serum and liver were significantly decreased in model + Benz group, whereas Ch
      HDL was raised in rats fed special HD (P<0.05). Calculated index of atherogenity
      (TCh - Ch-HDL) / (Ch-HDL) showed the positive effect. Conclusion: The results
      obtained were shown the hypolipidemic activity of N-cholinergic antagonist
      Benzohexonium (20 mg/kg) lowered the content of lipids in blood, liver, and
      aorta.

PMID- 29215245
TI  - A Chief's Worst Day: Director of Hamilton County EMS reviews school bus rollover
      MCI.

PMID- 29215246
TI  - [The role of inflammatory and immune reactivity in developing pain in adenomyosis
      ].
AB  - Objective: to analyze the role of inflammatory and immune reactivity in the
      development of adenomyosis and its associated pain. Methods. For morphological
      studies it were using fragments of walls of 56 uterus received after hysterectomy
      in patients with pelvic pain on a background of diffuse adenomyosis II-III
      degree, and 30 patients with painless form of adenomyosis. To identify, evaluate
      the amount and spatial distribution of macrophages, T-helper cells and natural
      killer cells it was using MAbs to CD68, CD4, CD56 respectively. The results of
      the study showed a significantly high expression of CD68 (49,3 +/- 2,3 vs. 21,2
      +/- 1,7 conv. units, p<0,01), CD56 (47,4 +/- 2,7 vs. 17.2 +/- 1.8 conv. units,
      p<0,01, p<0,05) and CD4 (52,1 +/- 2,2 vs. 19,9 +/- 2,5 conv. units, p<0,01) in
      patients with painful form of adenomyosis in the regions of ectopic endometrium
      and in the regions of perivascular growth in myometrium compared to those areas
      in women with painless adenomyosis. Conclusions: Adenomyosis is a chronic
      inflammatory disease accompanied by dysfunction of the uterine immune reactivity.
      Inflammatory and immune processes in the uterus with adenomyosis contribute to
      the persistence and growth of endometrial implants. In adenomyosis, associated
      with chronic pelvic pain syndrome, there is increase in the number of activated
      macrophages, natural killer cells and T-helper cells in the perivascular regions
      and in areas of remodeling of the myometrium are carriers of the nerves, which
      leads to increased neurogenic inflammation and sensitivity of nociceptors,
      activation of peripheral nerve fibers and the generation of pain.

PMID- 29215247
TI  - Red Lights and Siren: High risk, high liability, little reward.

PMID- 29215248
TI  - [Systemic errors in the estimation of systemic arterial pressure via transfer
      functions after experimental changes of the circulating blood volume].
AB  - The results of the experimental studies reveal the decrease of vascular rigidity
      with the increase of systemic error of the arterial pressure values estimated via
      implication of transfer functions following haemorrhage modeling in rats.
      Compensation of the circulating blood volume by means of dextran infusion
      resulted in restoration of both vascular rigidity and systemic error of estimated
      arterial pressure. The results can be put into medical practice as an approach
      for testing of non-invasive methods in cardiovascular research.

PMID- 29215249
TI  - [The role of lipoprotein-associated enzyme paraoxonase 1 and its polymorphisms in
      the pathogenesis of endothelial dysfunction and somatic complications in patients
      with alcoholism: Review ].
AB  - A review of recent data on the role of the multifunctional enzyme, associated
      with high density lipoproteins - paraoxonase 1 (PON1) in maintaining healthy
      endothelial function by detoxifying both oxidized low density lipoproteins and
      homocysteine thiolactone. The additional contribution to the protection of the
      endothelium against damage makes organophosphatase activity of PON1 involved in
      the detoxification products of tobacco smoke. The reduction of antioxidant
      activity of PON1 promotes the differentiation of monocytes into macrophages and
      the development of inflammation. The reduction of thiolactonase activity of PON1
      is accompanied by a decrease of methionine re-synthesis from homocysteine causing
      DNA- hypomethylation and alteratioin of the expression patterns of pro- and anti
      atherogenic genes. Global hypomethylation of the genome is regarded as one of the
      three most important mechanisms of the increased risk of somatic complications of
      alcoholism. The accumulation of homocysteine thiolactone serving agonist of
      glutamate receptors and antagonist of dopamine receptors is a prerequisite to
      increased alcohol abuse. Clinical observations focusing on gene polymorphisms of
      PON indicate that three different genotypes of polymorphism PON1Q192R have
      unequal degrees atheroprotective properties.

PMID- 29215250
TI  - [Macrophage activation in atherosclerosis. Message 2. Effects of factors on
      macrophage activation].
AB  - In atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly
      adjust to changing microenvironmental conditions. In the plaque, serum lipids,
      serum lipoproteins and various pro- or anti-inflammatory stimuli such as
      cytokines, chemokines and small bioactive molecules could greatly influence the
      macrophage phenotype inducing switch towards more proinflammatory or anti
      inflammatory properties. Dynamic plasticity of macrophages is achieved by up
      regulation and down-regulation of overlapping set of transcription factors that
      drive macrophage polarization. Understanding of mechanisms of macrophage
      plasticity and resolving functional characteristics of distinct macrophage
      phenotypes should help in the development of new strategies for treatment of
      chronic inflammation in cardiovascular disease.

PMID- 29215251
TI  - [Modern methods of diagnosis dyslipidemia ].
AB  - Dyslipidemia is abnormalities of lipid and lipoprotein metabolism. Most
      dyslipidemias are hyperlipidemias; that is an abnormally high level of lipids
      and/or lipoproteins in the blood. Lipid and lipoprotein abnormalities are common
      in the general population, and are regarded as a modifiable risk factor for
      cardiovascular disease due to their influence on atherosclerosis. Primary
      dyslipidemia is usually due to genetic causes, while secondary dyslipidemia
      arises due to other underlying causes such as diabetes mellitus. Thus,
      dyslipidemia is an important factor in the development of atherosclerosis and
      cardiovascular diseases therefore, it is important to diagnose it in time. This
      review focuses on the modern methods of diagnosis of dyslipidemia.

PMID- 29215252
TI  - [Current status of vascular remodeling and angiogenesis in chronic liver
      diseases].
AB  - The review focuses on the analysis of researches on the pathophysiology of liver
      vascular bed, mesenteric vessels, as well as the characteristics of angiogenesis
      in CLD. The results of this review shows that one of the most important areas of
      research is soluble vascular endothelial growth factor receptors, disclosing
      their importance for prognosis and treatment of diseases that occur with severe
      disorders of angiogenesis, including in CLD.

PMID- 29215253
TI  - [Melatonin as a universal modulator of any pathological processes ].
AB  - In paper reviewed own and numerous literary data about of universal modulated and
      limited influences of melatonin, which produced by pineal gland and peripheral
      tissues cells, on any pathological processes in the cerebral brain and internal
      organs. Cellular and systemic mechanisms of its protective and modulated
      properties were observed.

PMID- 29215254
TI  - Boerhaave's : Providers challenged by patient in compensatory stage of shock.

PMID- 29215255
TI  - [Applying HIFU for the obliteration of the veins in the experiment ].
AB  - The effect of high-intensity focused ultrasound (HIFU) on venous wall structure
      was studied in the rabbit model. Special setup was developed for ultrasound
      generation and vessel targeting. Methods. The essential part of the setup is
      spherical focusing power irradiator with following characteristics: power supply
      voltage of 25 V, frequency of 1.9 MHz, ultrasound intensity in the focal spot
      ~8.7 kW/cm2. Results. Single 15-s exposure of the femoral vein to HIFU resulted
      in partial desquamation of the endothelium, vacuolization of myocyte cytoplasm,
      misarrangement and coagulation of collagen fibers. Pulsed HIFU (5 pulses for 5 s
      each) caused protein coagulation in all layers of venous wall (v. cava posterior)
      as well as the appearance of the areas of fibrinoid necrosis, severe endothelial
      desquamation, and intimal detachment. HIFU-induced collagen structural changes in
      media and adventitia of the vein suggest that HIFU exposure resulted in local
      temperature increase up to ~60 degrees S. In some experiments, adjacent to the
      vein muscles were also exposed to HIFU. In this case, edema of the interstitium
      and muscle fibers was registered, as well as fragmentation and coagulation of
      some fibers, altered staining patterns and neutrophil infiltration. These changes
      could be attributed to the development of acute muscle injury (acute fasciitis).
      Perivascular adipose tissue also demonstrated edema and lipolysis, red blood cell
      diapedesis, and leukocyte infiltration. Conclusion. The observations on
      structural changes in the venous wall after HIFU exposure could lay the ground
      for future experiments on HIFU - mediated obliteration.

PMID- 29215256
TI  - [Registration of the protein in the serum with a field-effect nanotransistor
      biosensor].
AB  - A method for detection of cancer-associated protein D-NFATc1 in serum using
      nanowire (NW) biosensor based on field-effect nanotransistor is developed. Field
      effect nanotransistor was fabricated on the basis of "silicon-on-insulator"
      structures. For the biospecific detection of target protein, the NW surface was
      modified with aptamers against the target protein. Using the 3 um-NW enabled to
      obtain stable source-drain characteristics and to register D-NFATc1 in serum at
      concentration of 2.5 x 1014 M in the mode of drain-source current vs. gate
      voltage characteristics measurements. Data collection in the mode of drain-source
      current vs. gate voltage characteristics measurements was carried out with the
      use of high-speed data collection system running TURBO NBS software.

PMID- 29215257
TI  - Starting Points: Integrating simulation into EMS education.

PMID- 29215258
TI  - Plasma-Functionalized Solution: A Potent Antimicrobial Agent for Biomedical
      Applications from Antibacterial Therapeutics to Biomaterial Surface Engineering.
AB  - Deadly diseases caused by pathogenic bacteria and viruses have increasingly
      victimized humans; thus, the importance of disinfection has increased in medical
      settings as well as in food and agricultural industries. Plasma contains multiple
      bactericidal agents, including reactive species, charged particles, and photons,
      which can have synergistic effects. In particular, the chemicals formed in
      aqueous solution during plasma exposure have the potential for high antibacterial
      activity against various bacterial infections. Here, we report the antibiotic
      potency of plasma-treated water (PTW). To illustrate the applicability of PTW for
      disinfecting biological substances, an Escherichia coli biofilm was used. We
      sought to identify the chemical species in PTW and investigate their separate
      effects on biofilm removal. Dielectric barrier discharge in ambient air was used
      to prepare the PTW and treat the biofilm directly. Hydrogen peroxide, ozone, and
      nitrites were identified as the long-lived reactive species in the PTW, whereas
      hydroxyl radicals and superoxide anions were identified as the short-lived
      reactive species in the PTW; all these species showed an ability to disinfect in
      biofilm removal.

PMID- 29215259
TI  - Novel Flexible Transparent Conductive Films with Enhanced Chemical and
      Electromechanical Sustainability: TiO2 Nanosheet-Ag Nanowire Hybrid.
AB  - Flexible transparent conductive films (TCFs) of TiO2 nanosheet (TiO2 NS) and
      silver nanowire (Ag NW) network hybrid were prepared through a simple and
      scalable solution-based process. The as-formed TiO2 NS-Ag NW hybrid TCF shows a
      high optical transmittance (TT: 97% (90.2% including plastic substrate)) and low
      sheet resistance (Rs: 40 Omega/sq). In addition, the TiO2 NS-Ag NW hybrid TCF
      exhibits a long-time chemical/aging and electromechanical stability. As for the
      chemical/aging stability, the hybrid TCF of Ag NW and TiO2 NS reveals a retained
      initial conductivity (DeltaRs/Rs < 1%) under ambient oxidant gas over a month,
      superior to that of bare Ag NW (DeltaRs/Rs > 4000%) or RuO2 NS-Ag NW hybrid
      (DeltaRs/Rs > 200%). As corroborated by the density functional theory simulation,
      the superb chemical stability of TiO2 NS-Ag NW hybrid is attributable to the
      unique role of TiO2 NS as a barrier, which prevents Ag NW's chemical corrosion
      via the attenuated adsorption of sulfidation molecules (H2S) on TiO2 NS. With
      respect to the electromechanical stability, in contrast to Ag NWs (DeltaR/R0 ~
      152.9%), our hybrid TCF shows a limited increment of fractional resistivity
      (DeltaR/R0 ~ 14.4%) after 200 000 cycles of the 1R bending test (strain: 6.7%)
      owing to mechanically welded Ag NW networks by TiO2 NS. Overall, our unique
      hybrid of TiO2 NS and Ag NW exhibits excellent electrical/optical properties and
      reliable chemical/electromechanical stabilities.

PMID- 29215260
TI  - Interfacial Adsorption of Monoclonal Antibody COE-3 at the Solid/Water Interface.
AB  - Spectroscopic ellipsometry (SE) and neutron reflection (NR) data for the
      adsorption of a monoclonal antibody (mAb, termed COE-3, pI 8.44) at the bare
      SiO2/water interface are compared here to the simulations based on Derjaguin
      Landau-Verwey-Overbeek theory. COE-3 adsorption was characterized by an initial
      rapid increase in the surface-adsorbed amount (Gamma) followed by a plateau. Only
      the initial rate of the increase in Gamma was strongly correlated with the bulk
      concentration (0.002-0.2 mg/mL), with Gamma at the plateau being about 2.2 mg/m2
      (pH 5.5). Simulations captured COE-3 adsorption at equilibrium most accurately,
      the point at which the outgoing flux of molecules within the adsorbed plane
      matched the adsorption flux. Increasing the buffer pH from 5.5 to 9 increased
      Gamma at equilibrium to ~3 mg/m2 (0.02 mg/mL COE-3), revealing a dominant role
      for lateral repulsion between adsorbed mAb molecules. In contrast, increasing the
      buffer ionic strength (pH 6) reduced Gamma, which was captured by simulations
      accounting for electrostatic screening by ions, in addition to mAb/SiO2
      attractive forces and lateral repulsion. NR data at the same bulk concentrations
      corroborated the SE data, albeit with slightly higher Gamma due to longer
      adsorption times for data acquisition; for example, at pH 9, Gamma was 3.6 mg/m2
      (0.02 mg/mL COE-3), equivalent to a relatively high volume fraction of 0.5. An
      adsorbed monolayer with a thickness of 50-52 A was consistently determined by NR,
      corresponding to the short axial lengths of fragment antigen-binding and fragment
      crystallization and implying minimal structural perturbation. Thus, the
      simulations enabled a mechanistic interpretation of the experimental data of mAb
      adsorption at the SiO2/water interface.

PMID- 29215261
TI  - An Interface Equilibria-Triggered Time-Dependent Diffusion Model of the Boundary
      Potential and Its Application for the Numerical Simulation of the Ion-Selective
      Electrode Response in Real Systems.
AB  - A simple dynamic model of the phase boundary potential of ion-selective
      electrodes is presented. The model is based on the calculations of the
      concentration profiles of the components in membrane and sample solution phases
      by means of the finite difference method. The fundamental idea behind the
      discussed model is that the concentration gradients in both membrane and sample
      solution phases determine only the diffusion of the components inside the
      corresponding phases but not the transfer across the interface. The transfer of
      the components across the interface at any time is determined by the
      corresponding local interphase equilibria. According to the presented model, each
      new calculation cycle begins with the correction of the components'
      concentrations in the near-boundary (first) layers of the membrane and solution,
      based on the constants of the interphase equilibria and the concentrations
      established at a given time as a result of diffusion. The corrected
      concentrations of the components in the boundary layers indicate the start of a
      new cycle every time with respect to the calculations of diffusion processes
      inside each phase from the first layer to the second one, and so on. In contrast
      to the well-known Morf's model, the above-mentioned layers do not comprise an
      imaginary part and are entirely localized in the corresponding phases, and this
      allows performing the calculations of the equilibrium concentrations by taking
      into account material balance for each component. The model remains operational
      for any realistic scenarios of the electrode functioning. The efficiency and
      predictive ability of the proposed model are confirmed by comparing the results
      of calculations with the experimental data on the dynamics of the potential
      change of a picrate-selective electrode in nitrate solutions when determining the
      selectivity coefficients using the methods recommended by IUPAC.

PMID- 29215262
TI  - Ultrasensitive Electroanalysis: Femtomolar Determination of Lead, Cobalt, and
      Nickel.
AB  - We demonstrate the feasibility of attaining femtomolar limits of quantitation in
      electroanalysis. The method employed is based on electrocatalytic amplification,
      where small quantities of metal deposit performed on a carbon electrode causes a
      large increase in the observed current, for example, for the oxidation of water.
      We show calibration curves at the femtomolar level for cobalt, nickel, and lead
      ions on carbon ultramicroelectrodes (CUMEs), ca. 500 nm radii. The CUME was
      biased at a potential where the ion would deposit as the metal oxide, MOx, and a
      high concentration of species that is oxidized at the deposit is present in
      solution. Blips were observed in the amperometric i-t response, and their
      frequency scaled linearly with the concentration of ions at the femtomolar level.
      From these results, the limits of quantitation for cobalt, nickel, and lead ions
      were reported at 10 s of femtomolar level for the first time.

PMID- 29215264
TI  - Tuning Bacterial Attachment and Detachment via the Thickness and Dispersity of a
      pH-Responsive Polymer Brush.
AB  - We investigated the effect of two brush parameters, thickness and dispersity in
      the molecular weight distribution, on the adhesion of bacteria to pH-responsive
      poly(acrylic acid) (PAA) brushes synthesized using surface-initiated atom
      transfer radical polymerization. The attachment and detachment of Staphylococcus
      epidermidis to PAA brushes at pH 4 and pH 9, respectively, were examined with
      confocal microscopy. An optimal range of brush thickness, 13-18 nm, was
      identified for minimizing bacterial adhesion on PAA brushes at pH 4, and
      bacterial attachment did not depend on the brush dispersity. Increasing either
      the brush thickness or dispersity detached bacteria from the brushes when the pH
      was increased from 4 to 9. Bacterial detachment likely arose from an enhanced
      actuation effect in thick or high-dispersity brushes, as PAA brushes change
      conformation from collapsed to extended states when the pH is increased from 4 to
      9. These results suggest that manipulating the molecular weight distribution
      provides a route to separately tune the attachment and detachment of bacteria.

PMID- 29215263
TI  - Library-to-Library Synthesis of Highly Substituted alpha-Aminomethyl Tetrazoles
      via Ugi Reaction.
AB  - alpha-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent
      reaction (MCR), were shown to be excellent starting materials for a further Ugi
      MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5
      yl)methyl)amino)acetamides having four points of diversity in a library-to
      library approach. The scope and limitations of the two-step sequence was explored
      by conducting more than 50 reactions. Irrespective of electron-rich and electron
      deficient oxo-components and the nature of the isocyanide component, the
      reactions give excellent yields. Sterically less hindered alpha-aminomethyl
      tetrazoles give better yields of in further Ugi MCR. The target scaffold has four
      points of diversity and is finding applications to fill screening decks for high
      throughput screening (HTS) in the European Lead Factory and in structure-based
      drug design.

PMID- 29215265
TI  - Probing Nanoparticle Plasmons with Electron Energy Loss Spectroscopy.
AB  - Electron energy loss spectroscopy (EELS) performed in a scanning transmission
      electron microscope (STEM) has demonstrated unprecedented power in the
      characterization of surface plasmons. The subangstrom spatial resolution achieved
      in EELS and its capability of exciting the full set of localized surface plasmon
      resonance (LSPR) modes supported by a metallic nanostructure makes STEM/EELS an
      ideal tool in the study of LSPRs. The plasmonic properties characterized using
      EELS can be associated with geometric or structural features collected
      simultaneously in a STEM to achieve a deeper understanding of the plasmonic
      response. In this review, we provide the reader a thorough experimental
      description of EELS as a LSPR characterization tool and summarize the exciting
      recent progress in the field of STEM/EELS plasmon characterization.

PMID- 29215268
TI  - Photodecomposition of Metal Nitrate and Chloride Compounds Yields Amorphous Metal
      Oxide Films.
AB  - UV light is found to trigger the decomposition of MClx or M(NO3)x (where M = Fe,
      Co, Ni, Cu, or Zn) to form uniform, amorphous films of metal oxides. This process
      does not elevate the temperature of the substrate and thus conformal films can be
      coated on a range of substrates, including rigid glass and flexible plastic. The
      formation of the oxide films were confirmed by a combination of powder X-ray
      diffraction, X-ray photoelectron spectroscopy, X-ray fluorescence spectroscopy,
      Fourier transform infrared spectroscopy and scanning electron microscopy
      techniques. Amorphous oxide films of iron, nickel and a combination of iron and
      nickel demonstrated oxygen evolution reaction electrocatalytic activities
      commensurate with films of the same compositions prepared by widely used
      electrodeposition and sputtering methods. These results illuminate a potential
      route to amorphous oxides at scale using simple metal precursors without vacuum
      or heat.

PMID- 29215267
TI  - New Structural Insights into Formation of the Key Actin Regulating WIP-WASp
      Complex Determined by NMR and Molecular Imaging.
AB  - Wiskott-Aldrich syndrome protein (WASp) is exclusively expressed in hematopoietic
      cells and responsible for actin-dependent processes, including cellular
      activation, migration, and invasiveness. The C-terminal domain of WASp
      Interacting Protein (WIP) binds to WASp and regulates its activity by shielding
      it from degradation in a phosphorylation dependent manner as we previously
      demonstrated. Mutations in the WAS-encoding gene lead to the primary
      immunodeficiencies Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia
      (XLT). Here, we shed a first structural light upon this function of WIP using
      nuclear magnetic resonance (NMR) and in vivo molecular imaging. Coexpression of
      fragments WASp(20-158) and WIP(442-492) allowed the purification and structural
      characterization of a natively folded complex, determined to form a
      characteristic pleckstrin homology domain with a mixed alpha/beta-fold and
      central two-winged beta-sheet. The WIP-derived peptide, unstructured in its free
      form, wraps around and interacts with WASp through short structural elements.
      Forster resonance energy transfer (FRET) and biochemical experiments demonstrated
      that, of these elements, WIP residues 454-456 are the major contributor to WASp
      affinity, and the previously overlooked residues 449-451 were found to have the
      largest effect upon WASp ubiquitylation and, presumably, degradation. Results
      obtained from this complementary combination of technologies link WIP-WASp
      affinity to protection from degradation. Our findings about the nature of
      WIP.WASp complex formation are relevant for ongoing efforts to understand
      hematopoietic cell behavior, paving the way for new therapeutic approaches to WAS
      and XLT.

PMID- 29215266
TI  - Use of Phenoxyaniline Analogues To Generate Biochemical Insights into the
      Interactio n of Polybrominated Diphenyl Ether with CYP2B Enzymes.
AB  - Human hepatic cytochromes P450 (CYP) are integral to xenobiotic metabolism.
      CYP2B6 is a major catalyst of biotransformation of environmental toxicants,
      including polybrominated diphenyl ethers (PBDEs). CYP2B substrates tend to
      contain halogen atoms, but the biochemical basis for this selectivity and for
      species specific determinants of metabolism has not been identified. Spectral
      binding titrations and inhibition studies were performed to investigate
      interactions of rat CYP2B1, rabbit CYP2B4, and CYP2B6 with a series of
      phenoxyaniline (POA) congeners that are analogues of PBDEs. For most congeners,
      there was a <3-fold difference between the spectral binding constants (KS) and
      IC50 values. In contrast, large discrepancies between these values were observed
      for POA and 3-chloro-4-phenoxyaniline. CYP2B1 was the enzyme most sensitive to
      POA congeners, so the Val-363 residue from that enzyme was introduced into CYP2B4
      or CYP2B6. This substitution partially altered the protein-ligand interaction
      profiles to make them more similar to that of CYP2B1. Addition of cytochrome P450
      oxidoreductase (POR) to titrations of CYP2B6 with POA or 2'4'5'TCPOA decreased
      the affinity of both ligands for the enzyme. Addition of cytochrome b5 to a
      recombinant enzyme system containing POR and CYP2B6 increased the POA IC50 value
      and decreased the 2'4'5'TCPOA IC50 value. Overall, the inconsistency between KS
      and IC50 values for POA versus 2'4'5'TCPOA is largely due to the effects of redox
      partner binding. These results provide insight into the biochemical basis of
      binding of diphenyl ethers to human CYP2B6 and changes in CYP2B6-mediated
      metabolism that are dependent on POA congener and redox partner identity.

PMID- 29215269
TI  - Lanthanum-Based Metal-Organic Frameworks for Specific Detection of Sudan Virus
      RNA Conservative Sequences down to Single-Base Mismatch.
AB  - Reactions of La(NO3)3.6H2O with the polar, tritopic quaternized carboxylate
      ligands N-carboxymethyl-3,5-dicarboxylpyridinium bromide (H3CmdcpBr) and N-(4
      carboxybenzyl)-3,5-dicarboxylpyridinium bromide (H3CbdcpBr) afford two water
      stable metal-organic frameworks (MOFs) of {[La4(Cmdcp)6(H2O)9]}n (1, 3D) and
      {[La2(Cbdcp)3(H2O)10]}n (2, 2D). MOFs 1 and 2 absorb the carboxyfluorescein (FAM)
      tagged probe DNA (P-DNA) and quench the fluorescence of FAM via a photoinduced
      electron transfer (PET) process. The nonemissive P-DNA@MOF hybrids thus formed in
      turn function as sensing platforms to distinguish conservative linear, single
      stranded RNA sequences of Sudan virus with high selectivity and low detection
      limits of 112 and 67 pM, respectively (at a signal-to-noise ratio of 3). These
      hybrids also exhibit high specificity and discriminate down to single-base
      mismatch RNA sequences.

PMID- 29215270
TI  - Microporous Cobalt(II)-Organic Framework with Open O-Donor Sites for Effective
      C2H2 Storage and C2H2/CO2 Separation at Room Temperature.
AB  - The self-assembly of a bifunctional organic ligand with a formate-bridged rod
      shaped secondary building unit leads to a new microporous metal-organic framework
      (MOF). This MOF shows a moderately high C2H2 storage capacity (145 cm3/g) and an
      excellent adsorption selectivity for C2H2/CO2 (11) at room temperature.
      Furthermore, its discriminatory sorption behavior toward C2H2 and CO2 was probed
      by computational analysis in detail.

PMID- 29215271
TI  - High Proton Conduction in Crystalline Composites Based on Preyssler-Type
      Polyoxometalates and Polymers under Nonhumidified or Humidified Conditions.
AB  - Keggin-type polyoxometalate (POM)-based compounds have long been considered as
      one of the environmentally friendly candidates of solid electrolytes exhibiting
      high proton conductivity under high relative humidity (RH >95%). However, their
      application has been limited by the lack of structural stability and large
      decrease in conductivity with a slight decrease in RH. In order to overcome these
      disadvantages, we report a series of crystalline composites based on Preyssler
      type POMs ([Na(H2O)P5W30O110]14-, [Bi(H2O)P5W30O110]12-), which are known to show
      higher acidity in comparison to Keggin-type POMs, and polymers (polyethylene
      glycol (PEG), polyallylamine (PAA)). Electrostatic interactions between POMs and
      polymers contribute to enhance the structural stability, and it has been widely
      known that polymer electrolytes promote cation transport via segmental motion of
      the polymer chain. In the crystalline composites, K+ acts as a linker to connect
      the POMs three-dimensionally, resulting in an all-inorganic framework, and
      polymers and waters of crystallization reside in the framework. The composites
      with PEG exhibit moderate proton conductivities of 10-4 S cm-1 under
      nonhumidified (RH <10%) and low-temperature (<368 K) conditions by the aid of
      segmental motion of PEG. The composite with PAA exhibits a high proton
      conductivity of 10-3 S cm-1 under humidified (RH 75%) and low-temperature (<338
      K) conditions.

PMID- 29215272
TI  - Expanded Helicenes: A General Synthetic Strategy and Remarkable Supramolecular
      and Solid-State Behavior.
AB  - A divergent synthetic strategy allowed access to several members of a new class
      of helicenes, the "expanded helicenes", which are composed of alternating
      linearly and angularly fused rings. The strategy is based on a three-fold,
      partially intermolecular [2+2+n] (n = 1 or 2) cycloaddition with substrates
      containing three diyne units. Investigation of aggregation behavior, both in
      solution and in the solid state, revealed that one of these compounds forms an
      unusual homochiral, pi-stacked dimer via an equilibrium that is slow on the NMR
      time scale. The versatility of the method was harnessed to access a selenophene
      annulated expanded helicene that, in contrast to its benzannulated analogue,
      exhibits long-range pi-stacking in the solid state. The new helicenes possess low
      racemization barriers, as demonstrated by dynamic 1H NMR spectroscopy.

PMID- 29215273
TI  - Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2
      ARE Pathway.
AB  - The cyanobacterial marine natural product honaucin A inhibits mammalian innate
      inflammation in vitro and in vivo. To decipher its mechanism of action, RNA
      sequencing was used to evaluate differences in gene expression of cultured
      macrophages following honaucin A treatment. This analysis led to the hypothesis
      that honaucin A exerts its anti-inflammatory activity through activation of the
      cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response
      element/electrophile response element (ARE/EpRE) signaling pathway. Activation of
      this pathway by honaucin A in cultured human MCF7 cells was confirmed using an
      Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural
      product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway
      through covalent interaction with the sulfhydryl residues of the cytosolic
      repressor protein Keap1. Honaucin A presents a potential therapeutic lead for
      diseases with an inflammatory component modulated by Nrf2-ARE.

PMID- 29215274
TI  - Cry11Aa Interacts with the ATP-Binding Protein from Culex quinquefasciatus To
      Improve the Toxicity.
AB  - Cry11Aa displays high toxicity to the larvae of several mosquito species,
      including Aedes, Culex, and Anopheles. To study its binding characterization
      against Culex quinquefasciatus, Cry11Aa was purified and western blot results
      showed that Cry11Aa could bind successfully to the brush border membrane
      vesicles. To identify Cry11Aa-binding proteins in C. quinquefasciatus, a biotin
      based protein pull-down experiment was performed and seven Cry11Aa-binding
      proteins were isolated from the midgut of C. quinquefasciatus larvae. Analysis of
      liquid chromatography-tandem mass spectrometry showed that one of the Cry11Aa
      binding proteins is the ATP-binding domain 1 family member B. To investigate its
      binding property and effect on the toxicity of Cry11Aa, western blot, far-western
      blot, enzyme-linked immunosorbent assay, and bioassays of Cry11Aa in the presence
      and absence of the recombinant ATP-binding protein were performed. Our results
      showed that the ATP-binding protein interacted with Cry11Aa and increased the
      toxicity of Cry11Aa against C. quinquefasciatus. Our study suggests that midgut
      proteins other than the toxin receptors may modulate the toxicity of Cry toxins
      against mosquitoes.

PMID- 29215275
TI  - X-Shaped Oligomeric Pyromellitimide Polyradicals.
AB  - The synthesis of stable organic polyradicals is important for the development of
      magnetic materials. Herein we report the synthesis, isolation, and
      characterization of a series of X-shaped pyromellitimide (PI) oligomers (Xn-R, n
      = 2-4, R = Hex or Ph) linked together by single C-C bonds between their benzenoid
      cores. We hypothesize that these oligomers might form high-spin states in their
      reduced forms because of the nearly orthogonal conformations adopted by their PI
      units. 1H and 13C nuclear magnetic resonance (NMR) spectroscopies confirmed the
      isolation of the dimeric, trimeric, and tetrameric homologues. X-ray
      crystallography shows that X2-Ph crystallizes into a densely packed
      superstructure, despite the criss-crossed conformations adopted by the molecules.
      Electrochemical experiments, carried out on the oligomers Xn-Hex, reveal that the
      reductions of the PI units occur at multiple distinct potentials, highlighting
      the weak electronic coupling between the adjacent redox centers. Finally, the
      chemically generated radical anion and polyanion states, Xn-Hex*- and Xn-Hexn(*
      ), respectively, were probed extensively by UV-vis-NIR absorption, EPR, and
      electron nuclear double resonance (ENDOR) spectroscopies. The ENDOR spectra of
      the radical monoanions Xn-Hex*- reveal that the unpaired electron is largely
      localized on a single PI unit. Further reductions of Xn-Hex*- yield EPR signals
      (in frozen solutions) that can be assigned to spin-spin interactions in X2-Hex2(*
      ), X3-Hex3(*-), and X4-Hex4(*-). Taken together, these findings demonstrate that
      directly linking the benzene rings of PIs with a single C-C bond is a viable
      method for generating stabilized high-spin organic anionic polyradicals.

PMID- 29215276
TI  - Removal of Nerve Agent Simulants from Water Using Light-Responsive Molecular
      Baskets.
AB  - We found that molecular baskets 1-3, with amino acids at their rim, undergo
      photoinduced decarboxylations to give baskets 4-6 forming a solid precipitate in
      water. Furthermore, organophosphonates 7-9 (OP), akin in size and shape to G-type
      nerve agents, form inclusion complexes with baskets 1-3 (K = 6-2243 M-1). Light
      irradiation (300 nm) of an aqueous solution of 1-3?OP led to the formation of
      precipitate containing an OP compound thereby amounting to a novel strategy for
      light-induced sequestration of nerve agents or, perhaps, other targeted
      compounds. Importantly, the stability of basket?OP complexes in addition to
      functional groups at the basket's rim play a role in the efficiency (up to 98%)
      by which OPs are removed from water.

PMID- 29215277
TI  - Review of the Scientific Understanding of Radioactive Waste at the U.S. DOE
      Hanford Site.
AB  - This Critical Review reviews the origin and chemical and rheological complexity
      of radioactive waste at the U.S. Department of Energy Hanford Site. The waste,
      stored in underground tanks, was generated via three distinct processes over
      decades of plutonium extraction operations. Although close records were kept of
      original waste disposition, tank-to-tank transfers and conditions that impede
      equilibrium complicate our understanding of the chemistry, phase composition, and
      rheology of the waste. Tank waste slurries comprise particles and aggregates from
      nano to micro scales, with varying densities, morphologies, heterogeneous
      compositions, and complicated responses to flow regimes and process conditions.
      Further, remnant or changing radiation fields may affect the stability and
      rheology of the waste. These conditions pose challenges for transport through
      conduits or pipes to treatment plants for vitrification. Additionally,
      recalcitrant boehmite degrades glass quality and the high aluminum content must
      be reduced prior to vitrification for the manufacture of waste glass of
      acceptable durability. However, caustic leaching indicates that boehmite
      dissolves much more slowly than predicted given surface normalized rates.
      Existing empirical models based on ex situ experiments and observations generally
      only describe material balances and have not effectively predicted process
      performance. Recent advances in the areas of in situ microscopy, aberration
      corrected transmission electron microscopy, theoretical modeling across scales,
      and experimental methods for probing the physics and chemistry at mineral-fluid
      and mineral-mineral interfaces are being implemented to build robustly predictive
      physics-based models.

PMID- 29215278
TI  - Rotamers of Isoprene: Infrared Spectroscopy in Helium Droplets and Ab Initio
      Thermochemistry.
AB  - Isoprene (C5H8) is an abundant, reactive tropospheric hydrocarbon, derived from
      biogenic emissions. A detailed understanding of the spectroscopy of isoprene is
      therefore desirable. Isoprene monomer is isolated in helium droplets and its
      infrared spectrum is measured in the CH stretching region. Anharmonic frequencies
      are predicted by VPT2+K simulations employing CCSD(T) force fields with quadratic
      (cubic and quartic) force constants computed using the ANO1 (ANO0) basis set. The
      vast majority of the spectral features can be assigned to trans-isoprene on the
      basis of these computations. Some features of the higher energy gauche conformer
      are also assignable, by comparison to experiments using heated isoprene.
      Convergent ab initio thermochemistry is presented for the isomerization pathway,
      for which the partition function explicitly accounts for the eigenstates
      associated with separate, uncoupled one-dimensional potential surfaces for methyl
      torsion and internal rotation between rotamers. The respective 0 and 298.15 K
      trans/gauche energy differences are 2.82 and 2.52 kcal/mol, which implies a room
      temperature gauche population of 2.8%.

PMID- 29215279
TI  - Design and Synthesis of Orally Bioavailable Piperazine Substituted 4(1H)
      Quinolones with Potent Antimalarial Activity: Structure-Activity and Structure
      Property Relationship Studies.
AB  - Malaria deaths have been decreasing over the last 10-15 years, with global
      mortality rates having fallen by 47% since 2000. While the World Health
      Organization (WHO) recommends the use of artemisinin-based combination therapies
      (ACTs) to combat malaria, the emergence of artemisinin resistant strains
      underscores the need to develop new antimalarial drugs. Recent in vivo efficacy
      improvements of the historical antimalarial ICI 56,780 have been reported,
      however, with the poor solubility and rapid development of resistance, this
      compound requires further optimization. A series of piperazine-containing 4(1H)
      quinolones with greatly enhanced solubility were developed utilizing structure
      activity relationship (SAR) and structure-property relationship (SPR) studies.
      Furthermore, promising compounds were chosen for an in vivo scouting assay to
      narrow selection for testing in an in vivo Thompson test. Finally, two piperazine
      containing 4(1H)-quinolones were curative in the conventional Thompson test and
      also displayed in vivo activity against the liver stages of the parasite.

PMID- 29215280
TI  - Correction to "Metal-Organic Framework Nodes as Nearly Ideal Supports for
      Molecular Catalysts: NU-1000- and UiO-66-Supported Iridium Complexes".

PMID- 29215281
TI  - Metabolic Effect of Dietary Taurine Supplementation on Nile Tilapia (Oreochromis
      nilotictus) Evaluated by NMR-Based Metabolomics.
AB  - Taurine is indispensable in aquatic diets that are based solely on plant protein,
      and it promotes growth of many fish species. However, the physiological and
      metabolome effects of taurine on fish have not been well described. In this
      study, 1H NMR-based metabolomics approaches were applied to investigate the
      metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to
      visualize the metabolic trajectory and reveal the possible mechanisms of
      metabolic effects of dietary taurine supplementation on tilapia growth. After
      extraction using aqueous and organic solvents, 19 taurine-induced metabolic
      changes were evaluated in our study. The metabolic changes were characterized by
      differences in carbohydrate, amino acid, lipid, and nucleotide contents. The
      results indicate that taurine supplementation could significantly regulate the
      physiological state of fish and promote growth and development. These results
      provide a basis for understanding the mechanism of dietary taurine
      supplementation in fish feeding. 1H NMR spectroscopy, coupled with multivariate
      pattern recognition technologies, is an efficient and useful tool to map the fish
      metabolome and identify metabolic responses to different dietary nutrients in
      aquaculture.

PMID- 29215282
TI  - Thermal Decomposition of Phosgene and Diphosgene.
AB  - Phosgene (COCl2) is a toxic compound used or formed in a wide range of
      applications. The understanding of its thermal decomposition for destruction
      processes or in the event of accidental fire of stored reserves is a major safety
      issue. In this study, a detailed chemical kinetic model for the thermal
      decomposition and combustion of phosgene and diphosgene is proposed for the first
      time. A large number of thermo-kinetic parameters were calculated using quantum
      chemistry and reaction rate theory. The model was validated against experimental
      pyrolysis data from the literature. It is predicted that the degradation of
      diphosgene is mainly ruled by a pericyclic reaction producing two molecules of
      phosgene and, to a lesser extent, by a roaming radical reaction yielding CO2 and
      CCl4. Phosgene is much more stable than diphosgene under high-temperature
      conditions, and its decomposition starts at higher temperatures. Decomposition
      products are CO and Cl2. An equimolar mixture of the latter molecules can be
      considered as a surrogate of phosgene from the kinetic point of view, but the
      important endothermic effect of the decomposition reaction can lead to different
      behaviors, for instance, in the case of autoignition under high pressure and high
      temperature.

PMID- 29215283
TI  - Water Adsorption and Dissociation on Polycrystalline Copper Oxides: Effects of
      Environmental Contamination and Experimental Protocol.
AB  - We use ambient-pressure X-ray photoelectron spectroscopy (APXPS) to study
      chemical changes, including hydroxylation and water adsorption, at copper oxide
      surfaces from ultrahigh vacuum to ambient relative humidities of ~5%.
      Polycrystalline CuO and Cu2O surfaces were prepared by selective oxidation of
      metallic copper foils. For both oxides, hydroxylation occurs readily, even at
      high-vacuum conditions. Hydroxylation on both oxides plateaus near ~0.01%
      relative humidity (RH) at a coverage of ~1 monolayer. In contrast to previous
      studies, neither oxide shows significant accumulation of molecular water; rather,
      both surfaces show a high affinity for adventitious carbon contaminants. Results
      of isobaric and isothermic experiments are compared, and the strengths and
      potential drawbacks of each method are discussed. We also provide critical
      evaluations of the effects of the hot filament of the ion pressure gauge on the
      reactivity of gas-phase species, the peak fitting procedure on the quantitative
      analysis of spectra, and rigorous accounting of carbon contamination on data
      analysis and interpretation. This work underscores the importance of considering
      experimental design and data analysis protocols during APXPS experiments with
      water vapor in order to minimize misinterpretations arising from these factors.

PMID- 29215284
TI  - Molecular-Scale Description of SPAN80 Desorption from a Squalane-Water Interface.
AB  - Extensive all-atom molecular dynamics calculations on the water-squalane
      interface for nine different loadings with sorbitan monooleate (SPAN80), at T =
      300 K, are analyzed for the surface tension equation of state, desorption free
      energy profiles as they depend on loading, and to evaluate escape times for
      adsorbed SPAN80 into the bulk phases. These results suggest that loading only
      weakly affects accommodation of a SPAN80 molecule by this squalane-water
      interface. Specifically, the surface tension equation of state is simple through
      the range of high tension to high loading studied, and the desorption free-energy
      profiles are weakly dependent on loading here. The perpendicular motion of the
      centroid of the SPAN80 headgroup ring is well-described by a diffusional model
      near the minimum of the desorption free-energy profile. Lateral diffusional
      motion is weakly dependent on loading. Escape times evaluated on the basis of a
      diffusional model and the desorption free energies are 7 * 10-2 s (into the
      squalane) and 3 * 102 h (into the water). The latter value is consistent with
      desorption times of related lab-scale experimental work.

PMID- 29215285
TI  - Anomalous Rate of H+ and D+ Excited-State Proton Transfer (ESPT) in H2O/D2O
      Mixtures: Irreversible ESPT in 1-Naphthol-4-sulfonate.
AB  - We employed steady-state and time-resolved fluorescence techniques to study the
      rates of excited-state proton and deuteron transfer (ESPT) from an irreversible
      photoacid, 1-naphthol-4-sulfonate, to solvent mixtures of H2O and D2O. We found
      that the overall ESPT rate to the solvent mixture does not follow a linear
      relation with the H2O mole ratio. We used a chemical kinetic model to explain the
      deviation of the ESPT rate constant from linear behavior with H2O mole ratio.
      There are three water species in the H2O-D2O mixtures, H2O, D2O, and HOD. There
      are six rate constants of H+ and D+ transfers to the three species. When the H2O
      mole ratio before mixing is 0.5, HOD mole ratio in the mixture is 0.5. The ESPT
      rate to HOD is much smaller than that of H+ transfer to neat H2O and hence the
      concave shape of the plot of ESPT rate constants versus the H2O molar ratio of
      the mixtures.

PMID- 29215286
TI  - Theoretical Phase Diagram for the Room-Temperature Electron-Hole Liquid in
      Photoexcited Quasi-Two-Dimensional Monolayer MoS2.
AB  - Strong correlations between electrons and holes can drive the existence of an
      electron-hole liquid (EHL) state, typically at high carrier densities and low
      temperatures. The recent emergence of quasi-two-dimensional (2D) monolayer
      transition metal dichalcogenides (TMDCs) provides ideal systems to explore the
      EHL state since ineffective screening of the out-of-plane field lines in these
      quasi-2D systems allows for stronger charge carrier correlations in contrast to
      conventional 3D bulk semiconductors and enables the existence of the EHL at high
      temperatures. Here we construct the phase diagram for the photoinduced first
      order phase transition from a plasma of electron-hole pairs to a correlated EHL
      state in suspended monolayer MoS2. We show that the quasi-2D nature of monolayer
      TMDCs and the ineffective screening of the out-of-plane field lines allow for
      this phase transition to occur at and above room temperature, thereby opening
      avenues for studying many-body phenomena without the constraint of cryogenics.

PMID- 29215287
TI  - Rh(III)-Catalyzed Cascade Annulations To Access Isoindolo[2,1-b]isoquinolin-5(7H)
      ones via C-H Activation: Synthesis of Rosettacin.
AB  - An efficient protocol for the synthesis of diversely substituted 7
      hydroxyisoindolo[2,1-b]isoquinolin-5(7H)-ones from the reaction of N
      (pivaloyloxy)benzamides with 2-alkynyl aldehydes has been developed, which
      proceeds through sequential alkyne insertion followed by addition of the amide
      nitrogen on to the aldehyde. This method provided the products with aminal
      functionality as a handle for further diversification. The synthetic utility of
      this strategy was successfully illustrated by the concise, two-step synthesis of
      an alkaloid, rosettacin, and a topoisomerase I inhibitor.

PMID- 29215289
TI  - Silver(I)- and Base-Mediated [3 + 3]-Cycloaddition of C,N-Cyclic Azomethine
      Imines with Aza-oxyallyl Cations.
AB  - A silver(I) and base-mediated [3 + 3]-cycloaddition reaction of in situ generated
      C,N-cyclic azomethine imines with in situ formed aza-oxyallyl cations is
      reported. This one-pot cycloaddition process shows broad substrate scope an
      excellent functional group tolerance and provides the corresponding biologically
      important isoquinoline-fused triazines in good to excellent yields.

PMID- 29215288
TI  - Palladium- and Nickel-Catalyzed Decarbonylative C-S Coupling to Convert
      Thioesters to Thioethers.
AB  - This Letter describes the development of a catalytic decarbonylative C-S coupling
      reaction that transforms thioesters into thioethers. Both Pd- and Ni-based
      catalysts are developed and applied to the construction of diaryl, aryl alkyl,
      and heterocycle-containing thioethers.

PMID- 29215290
TI  - Photocatalytic Synthesis of gamma-Lactones from Alkenes: High-Resolution Mass
      Spectrometry as a Tool To Study Photoredox Reactions.
AB  - A mild photocatalytic manifold for the synthesis of gamma-lactones has been
      developed. Utilizing Ru(bpy)3Cl2 as the photocatalyst, a cheap and reproducible
      synthetic protocol for gamma-lactones has been introduced. Mechanistic studies
      revealed the successful monitoring of photocatalytic reactions and radical
      intermediates via high-resolution mass spectrometry.

PMID- 29215291
TI  - One-Pot Synthesis of Difluoromethyl Thioethers from Thiourea and Diethyl
      Bromodifluoromethylphosphonate.
AB  - A straightforward one-pot synthesis of difluoromethyl thioethers from thiourea
      and diethyl bromodifluoromethylphosphonate has been developed. Thiourea is a
      cheap and friendly sulfur reagent, while diethyl bromodifluoromethylphosphonate
      is a low-cost and stable difluorocarbene precursor. The strategy enabled the
      introduction of SCF2H moieties into indoles, pyrroles, and activated arenes and
      formed a number of difluoromethyl thioethers.

PMID- 29215292
TI  - Scalable Electrochemical Dehydrogenative Lactonization of C(sp2/sp3)-H Bonds.
AB  - A practical, electrochemical method is developed for the direct dehydrogenative
      lactonization of C(sp2/sp3)-H bonds under external oxidant- and metal-free
      conditions, delivering diverse lactones, including coumarin derivatives with
      excellent regioselectivity. The scalable nature of this newly developed
      electrochemical process was demonstrated on a 40 g scale following an
      operationally simple protocol. The remote lactonization of C(sp3)-H bonds would
      constitute an important synthetic advance toward electrochemical C-O bond
      formation.

PMID- 29215293
TI  - Approach to Introducing Substituent on the Dipole Conjugate Chain: The D-pi-A
      Methine Chain Electrophilic Substitution.
AB  - The D-pi-A methine chain electrophilic substitution reactions for directly
      introducing some functional groups to the dipole conjugate chain, with mild
      conditions and good yields, are disclosed. This method is shown to efficiently
      replace the hydrogen on the D-pi-A methine chain with an electrophile to
      synthesize methine-substituted Cy3.5 in one step.

PMID- 29215294
TI  - Structure Reconstruction of LyP-1: Lc(LyP-1) Coupling by Amide Bond Inspires the
      Brain Metastatic Tumor Targeted Drug Delivery.
AB  - The stability and binding affinity of targeting ligands are very important in
      active targeting drug delivery. Herein we used LyP-1 peptide as a model peptide
      to investigate chemical-biology-based strategies in the design of peptide ligands
      for active targeting. LyP-1 is a short peptide cyclized with a disulfide bond. It
      can specifically bind to tumor cells and tumor lymphatics through the interaction
      with cell-surface protein p32/gC1qR. Lc(LyP-1), with a same sequence of LyP-1, is
      coupled by amide bond. It showed better cellular uptake and stability in blood in
      our previous research. Further, usually d-peptide demonstrates higher stability
      than l-peptide, and it may contribute to better active targeting ability in vivo.
      Herein, we designed a retro-inverso isomer of Lc(LyP-1), termed Dc(LyP-1),
      expecting to inspire brain metastatic tumor targeted drug delivery. However,
      although Lc(LyP-1) showed lower stability than Dc(LyP-1) in fresh rat bold serum,
      both the 4T1 cellular uptake capacity (89.20%) and p32 protein binding affinity
      (7.39 * 10-6) were significantly higher than those (33.41%, 1.37 * 10-5) of
      Dc(LyP-1). Further, Lc(LyP-1) modified PEG-PLA micelles displayed much higher in
      vivo distribution in brain metastatic tumor than Dc(LyP-1). All results suggested
      that Lc(LyP-1) had a better performance than Dc(LyP-1) in brain metastatic tumor
      targeted drug delivery.

PMID- 29215296
TI  - Identifying risk for language impairment in children from linguistically diverse
      low-income schools.
AB  - PURPOSE: To improve screening procedures for children in a linguistically diverse
      context, we combined tasks known to reveal grammatical deficits in children with
      language impairment (LI) with training to facilitate performance on a verb
      elicitation task. METHOD: Sixty-four first grade children participated. The
      objective grammatical measures included elicitation of 12 past tense regular
      verbs preceded by a teaching phase (teach-test), the sentence recall (SR) subtest
      of the Clinical evaluation of language fundamentals (CELF-4), and a tally of all
      conjugated verbs from a narrative retell task. Given the widespread reliance on
      teacher observation for the referral of children suspected of having LI, we
      compared our results to the spoken language portion of the CELF-4 teacher
      observational rating scale (ORS). RESULT: Using teacher observation as a
      reference for comparison, the past tense elicitation task and the SR task yielded
      strong discriminating power, but the verb tally was relatively weak. However,
      combining the three tasks yielded the highest levels of sensitivity (75%) and
      specificity (92%) than any single measure on its own. CONCLUSION: This study
      contributes to alternative assessment practices by highlighting the potential
      utility of adding a teaching component prior to administering informal
      grammatical probes.

PMID- 29215295
TI  - Quantitative Proteomic Study Reveals Up-Regulation of cAMP Signaling Pathway
      Related Proteins in Mild Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI), as a neurological injury, becomes a leading cause
      of disability and mortality due to lacking effective therapy. About 75% of TBI is
      mild traumatic brain injury (mTBI). However, the complex molecular mechanisms
      underlying mTBI pathophysiology remains to be elucidated. In this study, iTRAQ
      based quantitative proteomic approach was employed to measure temporal-global
      proteome changes of rat brain tissues from different time points (1 day, 7 day
      and 6 months) post single mTBI (smTBI) and repetitive mTBI (rmTBI). A total of
      5169 proteins were identified, of which, 237 proteins were significantly changed
      between control rats and mTBI model rats. Fuzzy c-means (FCM) clustering analysis
      classified these 237 proteins into six clusters according to their temporal
      pattern of protein abundance. Functional bioinformatics analysis and protein
      protein interaction (PPI) network mapping of these FCM clusters showed that
      phosphodiesterase 10A (Pde10a) and guanine nucleotide-binding protein G (olf)
      subunit alpha (Gnal) were the node proteins in the cAMP signaling pathway. Other
      biological processes, such as cell adhesion, autophagy, myelination, microtubule
      depolymerization and brain development, were also over-represented in FCM
      clusters. Further Western Blot experiments confirmed that Pde10a and Gnal were
      acutely up-regulated in severity-dependent manner by mTBI, but these two proteins
      could not be down-regulated to basal level at the time point of 6 months post
      repetitive mTBI. Our study demonstrated that different severity of mTBI cause
      significant temporal profiling change at the proteomic level and pointed out the
      cAMP signaling pathway-related proteins, Pde10a and Gnal, may play important
      roles in the pathogenesis and recovery of mTBI.

PMID- 29215297
TI  - Virulence Genes and Antimicrobial Resistance in Escherichia coli from Cheese Made
      from Unpasteurized Milk in Brazil.
AB  - Cow raw milk cheese is widely eaten in Brazil. These products may be contaminated
      with pathogenic bacteria. In this work, we investigated the presence of
      Escherichia coli in raw milk cheese from different States in Brazil. From 147
      "Minas" cheese samples, 28 cheeses were positive for E. coli. Among 39 E. coli
      isolates of the cheeses, one was positive for eae and negative for bpfA and
      efa1/lifA using PCR, and so was classified as atypical Enteropathogenic E. coli
      (aEPEC). Two other isolates were positive for extraintestinal pathogenic E. coli
      (ExPEC) genes. The aEPEC isolate belongs to serogroup O127 and was classified in
      A phylogenetic group, and ExPEC isolates were found in O73:H12 (EC-2 strain) and
      O64474:H8 (EC-9 strain) serotype. This ExPEC belongs to A and C phylogenetic
      group, respectively. Most of E. coli strains belonged to Clermont phylogenetic
      groups A (28.2%), C, and E (23.1%). Six strains (15.4%) of E. coli were positive
      for group B1 and two (5.1%) for B2. E. coli isolates presented an aggregative
      (46.0%) and diffuse (12.6%) adherence pattern to HeLa cells, and the other
      isolates did not show adhesion (41.4%). Four E. coli isolates (10.3%) were shown
      to produce moderate biofilm. The antimicrobial resistance rate was tetracycline
      (25.6%), followed by ampicillin (17.9%), cefoxitin (7.7%), nalidixic acid (5.1%),
      and amoxicillin-clavulanic acid (2.6%). One strain was resistant to three
      antimicrobials (tetracycline, ampicillin, and nalidixic acid). The presence of
      these microorganisms, the O127 strain, and a new serogroup in Brazil is a
      potential risk for public health.

PMID- 29215298
TI  - Echinacea purpurea Protects Against Restraint Stress-Induced Immunosuppression in
      BALB/c Mice.
AB  - Echinacea purpurea has been widely used for the prevention and treatment of upper
      respiratory tract infections and the common cold. The restraint stress has been
      reported to suppress a broad spectrum of immune functions. The aim of this study
      was to investigate the protective effects of the pressed juice of E. purpurea
      (L.) Moench (EFLA(r)894; Echinacea) against restraint stress-induced
      immunosuppression in BALB/c mice. Echinacea significantly normalized the
      restraint stress-induced reduction in splenocyte proliferation and splenic
      natural killer (NK) cell activity (P < .05). Echinacea treatment significantly
      increased the percentages of CD4+ and CD8+ T lymphocytes in the blood (P < .05).
      In addition, Echinacea restored serum cytokine levels, including interleukin-6
      (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17), as well as the mRNA
      expressions of these cytokines in spleen (P < .05). Our findings suggest that
      Echinacea might have beneficial effects on restraint stress-induced
      immunosuppression by increasing splenocyte proliferation and NK cell activity,
      while modulating T lymphocyte subsets and cytokine levels in the blood.

PMID- 29215300
TI  - Dental anomalies in different growth and skeletal malocclusion patterns.
AB  - OBJECTIVES: To evaluate prevalence, distribution, and sexual dimorphism of dental
      anomalies (DA) among different skeletal malocclusions (SM) and growth patterns
      (GP) under the hypothesis that specific clinical patterns exist and may indicate
      common etiological roots. MATERIALS AND METHODS: A total of 1047 orthodontic
      records of patients older than 8 years were evaluated. The SN-GoGn angle was used
      to classify GP (hypodivergent, normal, and hyperdivergent), and the ANB angle was
      used to verify SM (Angle Classes I, II, and III). These assessments were done
      from lateral cephalometric radiographs. DA were diagnosed using panoramic
      radiographs by one calibrated investigator. Odds ratios, chi-square, and
      Student's t-tests were used. RESULTS: Of the subjects, 56.7% were female, with
      mean age of 16.41 (+/-10.61) years. The prevalence of DA was 15.7%. Impaction and
      tooth agenesis were the most prevalent DA, with relative frequencies of 14.4% and
      9.7%, respectively. DA were most prevalent in Class III SM (80.8%) and in
      hypodivergent GP (82.5%), although this was not statistically significant. Tooth
      agenesis ( P < .01) and microdontia ( P = .025) were significantly more common
      among hypodivergent GP and Class III SM, respectively. CONCLUSIONS: The results
      of this study support the idea that DA are preferentially associated with certain
      patterns of malocclusion.

PMID- 29215299
TI  - Complex Assessment of Metabolic Effectiveness of Insulin Pump Therapy in Patients
      with Type 2 Diabetes Beyond HbA1c Reduction.
AB  - BACKGROUND: This prospective single-center study recruited insulin-resistant
      continuous subcutaneous insulin infusion (CSII) therapy-naive patients with type
      2 diabetes (T2D) using insulin analog-based multiple daily injections (MDI)
      therapy and metformin. METHODS: A total of 23 individuals with T2D (70% male),
      aged a mean +/- standard deviation 57.2 +/- 8.03 years, with body mass index of
      36.2 +/- 7.02 kg/m2, diabetes duration of 13.3 +/- 4.64 years, and HbA1c of 10.0%
      +/- 1.05% were randomly assigned to a CSII arm or an MDI continuation arm to
      explore glucose control, weight loss, total daily insulin dose (TDD), and insulin
      resistance. Insulin dosing was optimized over a 2-month run-in period. RESULTS:
      At 6 months, patients assigned to the CSII arm achieved a significant mean HbA1c
      reduction of -0.9% (95% confidence interval [CI] = -1.6, -0.1), while reducing
      their TDD by -29.8 +/- 28.41 U/day (33% of baseline [92.1 +/- 20.35 U/day]) and
      achieving body mass (BM) reduction of -0.8 +/- 5.61 kg (0.98% of baseline [104.8
      +/- 16.15 kg]). MDI patients demonstrated a nonsignificant HbA1c reduction of 
      0.3% (95% CI = -0.8, 0.1) with a TDD reduction of 5% from baseline (99.0 +/-
      25.25 U/day to 94.3 +/- 21.25 U/day), and a BM reduction of -1.0 +/- 2.03 kg
      (0.99% of baseline [108.9 +/- 20.55 kg]). After 6 months, the MDI arm crossed
      over to CSII therapy. At 12 months, patients continuing CSII demonstrated an
      additional mean 0.7% HbA1c reduction with 54.6% achieving HbA1c<8%. The final TDD
      reduction was -9.7 U/day in comparison to baseline; BM increased by 1.1 +/- 6.5
      kg from baseline. The MDI patients that crossed to CSII showed an HbA1c reduction
      of -0.5% +/- 1.04%, HbA1c response rate of 27.3%, a TDD reduction of -17.4 +/-
      21.06 U/day, and a BM reduction of -0.3 +/- 3.39 kg. Diabetic ketoacidosis or
      severe hypoglycemia did not occur in either arm. CONCLUSION: CSII therapy safely
      and significantly improved metabolic control with less insulin usage, with no
      sustainable reduction of BM, blood pressure, and lipid profile, in insulin
      resistant T2D patients. Treatment adherence and satisfaction in these patients
      were excellent.

PMID- 29215301
TI  - The positioning of Aboriginal students and their languages within Australia's
      education system: A human rights perspective.
AB  - This paper is a critical review of past and present languages policies in
      Australian schooling. We highlight the One Literacy movement that contravenes the
      human rights of Australia's Aboriginal students. This in turn impacts students'
      right to freedom of opinion and expression as stated in Article 19 of the
      Universal Declaration of Human Rights. The One Literacy movement operates by
      equating Standard Australian English literacy acquisition with Australia's global
      competitiveness and economic success. There is only one pathway through the
      Australian English curriculum with common assessments and standards. However, the
      Australian Curriculum provides three distinctive pathways when students from an
      English-speaking background learn languages other than English. We reveal this
      double standard, where current educational policies prioritise the languages of
      trade (e.g. Chinese) and accommodate speakers of these languages. Meanwhile
      Aboriginal-language-speaking students are not provided with the same
      accommodations. For educational equity, there should be a distinctive English
      language learner pathway that recognises that the majority of remote Aboriginal
      students from the Northern Territory are learning English as an additional
      language. We advocate for these changes because all children have a right to an
      appropriate education that will enable them to flourish as learners and citizens.

PMID- 29215302
TI  - Treatment of Goiter with Traditional Chinese Medicine Regimen Xing Qi Hua Ying
      Tang: A Clinical Study on 72 Patients with Multinodular and Diffuse Goiter.
AB  - OBJECTIVE: The present work aimed to further explore the therapeutic potential of
      Xing Qi Hua Ying Tang (XQHYT) by conducting a systemic clinical study in patients
      with goiter. DESIGN: Seventy-two patients with either multinodular or diffuse
      goiter were enrolled and randomly assigned into treatment group receiving XQHYT
      (n = 36) and control group receiving Hai Zao Yu Hu Tang (n = 36). LOCATION:
      Traditional Chinese Medicine Hospital of Shanxi. SUBJECTS: Patients were
      diagnosed multinodular goiter or diffuse goiter resulting from Qi stagnation.
      INTERVENTION: All patients took the extract twice a day (100 mL each time) for
      two courses of treatment, of which a single course lasted for 3 months. Before
      the treatment was commenced and after the completion of the treatment, general
      body checks, thyroid function test, and goiter size examination were performed.
      OUTCOME MEASURES: Scoring of the clinical symptoms using Chinese medicine
      symptomatology was also done. RESULTS: The symptom score of the treatment group
      was significantly lower than that of the control group (treatment group, 8.26 +/-
      2.62; control group, 10.02 +/- 2.62; p < 0.05). Substantial reduction in goiter
      size was seen in 82.3% of XQHYT-treated patients, whereas in the control group
      only 67.7% of patients exhibited constricted goiter. When assessed by both the
      Chinese medicine criteria and goiter size, the overall effective rate of the
      treatment group was 91.2%, whereas that of the control group was only 67.7%. The
      difference was statistically significant (p < 0.05). XQHYT did not affect the
      normal functions of liver, kidney, and heart. For both groups of patients, their
      levels of thyroid-stimulating hormone, free T4 and free T3 were normal before the
      treatment, and were not affected by the treatment. CONCLUSION: XQHYT was shown to
      be a promising therapeutic regimen for the treatment of goiter. The herbal
      regimen ameliorated clinical symptoms of patients that were accompanied with
      reduction in the size of goiter.

PMID- 29215304
TI  - Weight gain changes in patients with aripiprazole monotherapy compared with
      aripiprazole-antidepressant polypharmacy in an outpatient sample.
AB  - OBJECTIVE: This study seeks to evaluate the weight gain effect within a community
      based population of patients with diagnoses of depression, mood disorder, and
      schizophrenia receiving aripiprazole over a period of at least 6 months. METHOD:
      The four million members of Kaiser Permanente of Southern California (KPSC) were
      queried for a four-year period between January 1, 2010 and December 31, 2013. The
      initial cohort comprised 25,682 KPSC members who received at least one dispense
      of aripiprazole. This initial cohort was split into those who received
      aripiprazole as a monotherapy ("Alone" group) and those who were given
      aripiprazole as part of a combination therapy. The group of patients that
      received aripiprazole and antidepressant with high serotonin reuptake inhibition
      we called "High" group while the group receiving aripiprazole and bupropion
      combination we called "Low" serotonin group. We compared the primary endpoint of
      mean percent weight change from baseline after 180 days of continuous treatment
      between the three groups. Three pairwise comparisons were made: High versus
      Alone, Low versus Alone, and Low versus High, using adjusted and unadjusted
      linear regression models. RESULTS: Within this population, patients on
      aripiprazole monotherapy showed statistically significant weight gain in all
      three groups. However, there was no statistically significant difference in
      weight gain between the aripiprazole monotherapy, the high serotonergic
      combination group, and the low serotonergic combination group. This finding
      applied even within the subset of patients who were considered obese (body mass
      index > 30). CONCLUSIONS: The results suggest that weight gain is unchanged by
      combination treatments, but further research is required.

PMID- 29215303
TI  - Influence of Cryopreservation Solution on the In Vitro Culture of Skin Tissues
      Derived from Collared Peccary (Pecari tajacu Linnaeus, 1758).
AB  - Skin vitrification is a promising and alternative tool for the conservation of
      biodiversity, especially for wild mammals, such as collared peccaries. Several
      factors can affect the success of this procedure, such as the cryoprotectant
      solution used. Therefore, this study was carried out to compare the efficiency of
      various vitrification solutions for recovery of viable cells after in vitro
      culture of cryopreserved skin tissues derived from the collared peccary, aiming
      to study the application in biobanking, where cellular use is not immediately
      required. Then, Dulbecco's modified Eagle's medium (DMEM) composed of 2.2 g/L
      sodium bicarbonate and 10% fetal bovine serum (FBS) was supplemented with 3.0 M
      ethylene glycol (EG) or 3.0 M dimethyl sulfoxide (DMSO) or 1.5 M EG plus 1.5 M
      DMSO with or without sucrose (SUC; 0.25 M) to produce six solutions for solid
      surface vitrification. After warming, skin tissues were cultured in vitro and
      recovered cells were analyzed for morphology, adhesion, subconfluence, and
      proliferative activity for developing the growth curve and determining the
      population doubling time (PDT), and viability by Trypan Blue. The vitrification
      did not alter the ability of the tissues to adhere to the culture dish, as well
      as the day of all explants with cell growth, subconfluence samples, subconfluence
      total time, and PDT (p > 0.05). Moreover, independent of the cryoprotectant
      solution used, the vitrification altered the day of all attached explants (p <
      0.05). Nevertheless, for viability after the first passage, only the EG-SUC
      (86.9%) and DMSO-SUC (91.4%) groups maintained viable cell recovery similar to
      the nonvitrified group (96.3%, p > 0.05). Additionally, for viability after the
      third passage, only the EG-SUC group maintained the cell quality (88.3%), when
      compared with the nonvitrified (97.8%, p > 0.05). In conclusion, DMEM with 10%
      FBS, 3.0 M EG, and 0.25 M sucrose was the most efficient solution for vitrifying
      collared peccary skin tissues, leading to the in vitro culture of viable cells.

PMID- 29215305
TI  - Cerebrovascular function and mitochondrial bioenergetics after ischemia
      reperfusion in male rats.
AB  - The underlying factors promoting increased mitochondrial proteins, mtDNA, and
      dilation to mitochondrial-specific agents in male rats following tMCAO are not
      fully elucidated. Our goal was to determine the morphological and functional
      effects of ischemia/reperfusion (I/R) on mitochondria using electron microscopy,
      Western blot, mitochondrial oxygen consumption rate (OCR), and Ca2+ sparks
      activity measurements in middle cerebral arteries (MCAs) from male Sprague Dawley
      rats (Naive, tMCAO, Sham). We found a greatly increased OCR in ipsilateral MCAs
      (IPSI) compared with contralateral (CONTRA), Sham, and Naive MCAs. Consistent
      with our earlier findings, the expression of Mitofusin-2 and OPA-1 was
      significantly decreased in IPSI arteries compared with Sham and Naive.
      Mitochondrial morphology was disrupted in vascular smooth muscle, but morphology
      with normal and perhaps greater numbers of mitochondria were observed in IPSI
      compared with CONTRA MCAs. Consistently, there were significantly fewer baseline
      Ca2+ events in IPSI MCAs compared with CONTRA, Sham, and Naive. Mitochondrial
      depolarization significantly increased Ca2+ sparks activity in the IPSI, Sham,
      Naive, but not in the CONTRA group. Our data indicate that altered mitochondrial
      structure and function occur in MCAs exposed to I/R and that these changes impact
      not only OCR but Ca2+ sparks activity in both IPSI and CONTRA MCAs.

PMID- 29215306
TI  - A peptide mimetic of tyrosine phosphatase STEP as a potential therapeutic agent
      for treatment of cerebral ischemic stroke.
AB  - Extensive research over the last two decades has advanced our understanding of
      the pathophysiology of ischemic stroke. However, current pharmacologic therapies
      are still limited to rapid reperfusion using thrombolytic agents, and
      neuroprotective approaches that can reduce the consequences of ischemic and
      reperfusion injury, are still not available. To bridge this gap, we have
      evaluated the long-term efficacy and therapeutic time window of a novel peptide
      based neuroprotectant TAT-STEP, derived from the brain-enriched and neuron
      specific tyrosine phosphatase STEP. Using a rat model of transient middle
      cerebral artery occlusion (90 min), we show that a single intravenous
      administration of the peptide at the onset of reperfusion (early) or 6 h after
      the onset of the insult (delayed) reduces mortality rate. In the surviving rats,
      MRI scans of the brain at days 1, 14 and 28 after the insult show significant
      reduction in infarct size and improvement of structural integrity within the
      infarcted area following peptide treatment, regardless of the time of
      administration. Behavioral assessments show significant improvement in normal
      gait, motor coordination, sensory motor function and spatial memory following
      early or delayed peptide treatment. The study establishes for the first time the
      therapeutic potential of a tyrosine phosphatase in ischemic brain injury.

PMID- 29215307
TI  - Effects of intravitreous sodium hydrosulfide on intraocular pressure and
      retinopathy in ocular hypertensive rats.
AB  - We investigated the possible neuroprotectant and intraocular pressure (IOP)
      lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a
      rodent model of experimental glaucoma. Glaucoma currently is treated by
      controlling IOP using medications and/or surgery. These methods are not entirely
      adequate for all patients. We divided 24 rats into three groups. For the control
      group, the right eye was treated with intravitreous saline. For the glaucoma
      group, ocular hypertension was induced by photocoagulating three episcleral veins
      and the limbal plexus of the right eye using an argon laser, then saline was
      injected into the vitreous of these eyes during the third week. For the NaSH
      group, rats were treated with intravenous NaSH 3 weeks after photocoagulation.
      IOP was measured each week during the 6 week experimental period. Coagulating the
      episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection
      of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of
      the retina and decreased the number of apoptotic cells. Intravitreous NaSH
      appeared to reduce IOP and to prevent IOP induced retinopathy in rats.

PMID- 29215308
TI  - The importance of small polar radiometabolites in molecular neuroimaging: A PET
      study with [11C]Cimbi-36 labeled in two positions.
AB  - [11C]Cimbi-36, a 5-HT2A receptor agonist PET radioligand, contains three methoxy
      groups amenable to [11C]-labeling. In pigs, [11C]Cimbi-36 yields a polar (M1) and
      a less polar (M2) radiometabolite fraction, while changing the labeling to
      [11C]Cimbi-36_5 yields only the M1 fraction. We investigate whether changing the
      labeling position of [11C]Cimbi-36 eliminates M2 in humans, and if this changes
      the signal-to-background ratio. Six healthy volunteers each underwent two dynamic
      PET scans; after injection of [11C]Cimbi-36, both the M1 and M2 fraction appeared
      in plasma, whereas only the M1 appeared after [11C]Cimbi-36_5 injection.
      [11C]Cimbi-36_5 generated higher uptake than [11C]Cimbi-36 in both neocortex and
      cerebellum. With the simplified reference tissue model mean neocortical non
      displaceable binding potential for [11C]Cimbi-36 was 1.38 +/- 0.07, whereas for
      [11C]Cimbi-36_5, it was 1.18 +/- 0.14. This significant difference can be
      explained by higher non-displaceable binding caused by demethylation products in
      the M1 fraction such as [11C]formaldehyde and/or [11C]carbon dioxide/bicarbonate.
      Although often considered without any impact on binding measures, we show that
      small polar radiometabolites can substantially decrease the signal-to-background
      ratio of PET radioligands for neuroimaging. Further, we find that [11C]Cimbi-36
      has a better signal-to-background ratio than [11C]Cimbi-36_5, and thus will be
      more sensitive to changes in 5-HT2A receptor levels in the brain.

PMID- 29215309
TI  - Can teacher-child relationships support human rights to freedom of opinion and
      expression, education and participation?
AB  - PURPOSE: This study explored how teacher-child relationships change over the
      early school years, in terms of closeness and conflict, whether these
      trajectories differ in type and frequency for children with typical development
      and children with speech and language concern (SLC), and whether the trajectories
      are associated with school outcomes at 12-13 years. METHOD: Participants were
      children, parents and teachers in the Longitudinal Study of Australian Children.
      Parents identified 2890 children with typical communication and 1442 children
      with SLC. Teacher-rated teacher-child closeness and conflict were collected
      biennially over six years. Academic and social-emotional outcomes were reported
      by teachers and children. Growth mixture modelling was conducted to generate
      teacher-child relationship trajectories and Wald's chi-square analyses were used
      to test the association between trajectories and school outcomes at 12-13 years,
      after controlling for a range of covariates including child's sex, language
      background, Indigenous status, age and socio-economic position. RESULT: In both
      groups, the majority of children had teacher-child relationship trajectories with
      sustained high closeness and low conflict that predicted positive outcomes at age
      12-13, but the SLC group was more at risk of less positive trajectories and
      poorer school outcomes. CONCLUSION: Close, less conflicted relationships with
      teachers may provide a supportive context for later language, literacy and social
      emotional development. This study highlights the role of teachers in supporting
      children in their development of communication and academic skills that will
      optimise their capacity for freedom of opinions and expression, education and
      participation, as enshrined in Articles 19, 26 and 27 of the Universal
      Declaration of Human Rights.

PMID- 29215310
TI  - Apolipoprotein E4 mediates insulin resistance-associated cerebrovascular
      dysfunction and the post-prandial response.
AB  - Metabolic dysfunction, commonly a result of diets high in saturated fats and
      sugar, is associated with impaired cognitive function and an increased risk of
      age-related cognitive decline (ACD) and Alzheimer's disease (AD). Compared to the
      E3 isoform of apolipoprotein (apoE), the E4 isoform is a major genetic risk
      factor for ACD, AD, and for developing cognitive impairments following various
      environmental challenges, including dietary challenges such as a high-fat diet
      (HFD). Both insulin resistance (IR) and E4 are associated with metabolic and
      vascular impairments. Deficits in cerebral metabolism and cerebrovascular
      function have been proposed as initiating events leading to these impairments. In
      the current study, we employed a model of human apoE targeted replacement mice
      and HFD-induced obesity to study the potential link between E4 and IR, at rest
      and following a postprandial challenge. HFD-induced IR was associated with
      impaired cognition, reduced cerebral blood volume and decreased glucose uptake.
      These effects were more profound in E4 than E3 mice. Furthermore, the cognitive,
      metabolic and cerebrovascular responses to an exogenous glucose load showed an
      apoE isoform-dependent response, with E4, but not E3 mice, acutely benefiting
      from a spike in blood glucose.

PMID- 29215311
TI  - Classification of breast cancer in ultrasound imaging using a generic deep
      learning analysis software: a pilot study.
AB  - OBJECTIVE: To train a generic deep learning software (DLS) to classify breast
      cancer on ultrasound images and to compare its performance to human readers with
      variable breast imaging experience. METHODS: In this retrospective study, all
      breast ultrasound examinations from January 1, 2014 to December 31, 2014 at our
      institution were reviewed. Patients with post-surgical scars, initially
      indeterminate, or malignant lesions with histological diagnoses or 2-year follow
      up were included. The DLS was trained with 70% of the images, and the remaining
      30% were used to validate the performance. Three readers with variable expertise
      also evaluated the validation set (radiologist, resident, medical student).
      Diagnostic accuracy was assessed with a receiver operating characteristic
      analysis. RESULTS: 82 patients with malignant and 550 with benign lesions were
      included. Time needed for training was 7 min (DLS). Evaluation time for the test
      data set were 3.7 s (DLS) and 28, 22 and 25 min for human readers (decreasing
      experience). Receiver operating characteristic analysis revealed non-significant
      differences (p-values 0.45-0.47) in the area under the curve of 0.84 (DLS), 0.88
      (experienced and intermediate readers) and 0.79 (inexperienced reader).
      CONCLUSION: DLS may aid diagnosing cancer on breast ultrasound images with an
      accuracy comparable to radiologists, and learns better and faster than a human
      reader with no prior experience. Further clinical trials with dedicated
      algorithms are warranted. Advances in knowledge: DLS can be trained classify
      cancer on breast ultrasound images high accuracy even with comparably few
      training cases. The fast evaluation speed makes real-time image analysis
      feasible.

PMID- 29215312
TI  - GSTM1 and GSTT1 Gene Polymorphisms, Gene-Gene Interaction, and Esophageal
      Carcinoma Risk: Evidence from an Updated Meta-Analysis.
AB  - BACKGROUND: Published data regarding the association between GSTM1 and/or GSTT1
      gene polymorphisms and esophageal cancer (EC) susceptibility remain inconclusive.
      To clarify these associations, a meta-analysis was conducted. METHODS: We
      conducted a comprehensive search in PubMed, Embase, and the China National
      Knowledge Infrastructure (CNKI) for all such manuscripts published as of May 1,
      2017. The pooled odds ratio (ORs) with confidence intervals (95% CI) were
      estimated for each study to assess the strength of the association. A subgroup
      analysis, a sensitivity analysis, and a publication bias analysis were also
      performed. RESULTS: Data from 41 studies comprising 5291 EC cases and 8191
      controls were available for analysis of the GSTM1 polymorphism, and data from 31
      studies comprising 4330 EC cases and 6558 controls were available for analysis of
      the GSTT1 polymorphism. Analyses of the GSTM1 polymorphisms demonstrated that
      there was a significantly increased EC risk in GSTM1 null genotype carriers (OR =
      1.319, 95% CI = 1.125-1.546, p for heterogeneity <0.001). In subgroup analyses by
      ethnicity, and categories of EC, a significantly increased EC risk was found in
      Asians (OR = 1.457, 95% CI = 1.212-1.751, p for heterogeneity <0.001) and
      patients whose histological type was unknown. Analyses of the GSTT1 polymorphisms
      indicated a positive correlation between the GSTT1 null genotype and the EC risk
      (OR = 1.233, 95% CI = 1.044-1.455, p for heterogeneity <0.001). In subgroup
      analyses stratified by ethnicity and categories of EC, similar statistical
      associations were observed in Asians, esophageal squamous cell carcinoma (ESCC)
      patients, and ESCC on Asian population. In the GSTM1-GSTT1 interaction analysis,
      we discovered remarkably enhanced EC risk for patients with the GSTM1 and GSTT1
      dual null genotypes (OR = 1.962, 95% CI = 1.178-3.268, p for heterogeneity
      <0.001) compared with the reference GSTM1 and GSTT1 dual positive genotype.
      CONCLUSIONS: We conclude that the GSTM1 and GSTT1 null genotypes are associated
      with increased genetic susceptibility to EC in the overall human population,
      particularly among Asians. In addition, our findings suggest that persons with a
      null genotype for both the GSTM1 and GSTT1 genes are at higher risk of developing
      EC. Further well-designed studies are needed to confirm these associations.

PMID- 29215315
TI  - Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and
      somatic disorders: an updated systematic review and meta-analysis.
AB  - During the last two decades, Internet-delivered cognitive behavior therapy (ICBT)
      has been tested in hundreds of randomized controlled trials, often with promising
      results. However, the control groups were often waitlisted, care-as-usual or
      attention control. Hence, little is known about the relative efficacy of ICBT as
      compared to face-to-face cognitive behavior therapy (CBT). In the present
      systematic review and meta-analysis, which included 1418 participants, guided
      ICBT for psychiatric and somatic conditions were directly compared to face-to
      face CBT within the same trial. Out of the 2078 articles screened, a total of 20
      studies met all inclusion criteria. Results showed a pooled effect size at post
      treatment of Hedges g = .05 (95% CI, -.09 to .20), indicating that ICBT and face
      to-face treatment produced equivalent overall effects. Study quality did not
      affect outcomes. While the overall results indicate equivalence, there have been
      few studies of the individual psychiatric and somatic conditions so far, and for
      the majority, guided ICBT has not been compared against face-to-face treatment.
      Thus, more research, preferably with larger sample sizes, is needed to establish
      the general equivalence of the two treatment formats.

PMID- 29215314
TI  - Prenatal Perceived Stress and Adverse Birth Outcomes Among Puerto Rican Women.
AB  - BACKGROUND: Preterm birth and low birthweight contribute substantially to the
      disproportionately high infant mortality rates experienced by Puerto Ricans in
      the United States. The purpose of this study was to examine whether the timing
      and pattern of prenatal psychosocial stress increased risk of adverse birth
      outcomes in this high-risk population. MATERIALS AND METHODS: Proyecto Buena
      Salud was a prospective cohort study conducted from 2006 to 2011 among
      predominantly Puerto Rican women. Participants (n = 1,267) were interviewed in
      early, mid-, and late pregnancy. We evaluated associations between early and mid
      pregnancy stress (Perceived Stress Scale) and preterm birth and low birthweight,
      and stress at each pregnancy time point and small for gestational age (SGA).
      RESULTS: Elevated levels of perceived stress in mid-pregnancy increased risk for
      preterm birth and low birthweight in adjusted analyses, with a linear trend
      observed for each increasing quartile of stress (ptrend = 0.01). Women in the
      highest quartile of stress experienced three times the risk for preterm birth
      (odds ratio [OR] = 3.50, confidence interval [95% CI]: 1.38-8.87) and low
      birthweight (OR = 3.53, 95% CI = 1.27-9.86) compared with women in the lowest
      quartile. Early pregnancy stress was not associated with preterm birth or low
      birthweight. Increase in stress from early to late pregnancy increased risk for
      SGA (OR = 1.90, 95% CI = 1.01-3.59); no associations were found between stress at
      any timepoint and SGA. CONCLUSION: Elevated levels of mid-pregnancy perceived
      stress increased risk for preterm birth and low birthweight, and an increase in
      stress over the course of pregnancy increased risk for SGA in a population of
      predominantly Puerto Rican women.

PMID- 29215316
TI  - Endothelial progenitor cells for cellular angiogenesis and repair: lessons
      learned from experimental animal models.
AB  - Stem/progenitor cell-based therapy has been extensively studied for angiomyogenic
      repair of the ischemic heart by regeneration of the damaged myocytes and
      neovascularization of the ischemic tissue through biological bypassing. Given
      their inherent ability to assume functionally competent endothelial phenotype and
      release of broad array of proangiogenic cytokines, endothelial progenitor cells
      (EPCs)-based therapy is deemed as most appropriate for vaculogenesis in the
      ischemic heart. Emulating the natural repair process that encompasses
      mobilization and homing-in of the bone marrow and peripheral blood EPCs, their
      reparability has been extensively studied in the animal models of myocardial
      ischemia with encouraging results. Our literature review is a compilation of the
      lessons learned from the use of EPCs in experimental animal models with emphasis
      on the in vitro manipulation and delivery strategies to enhance their retention,
      survival and functioning post-engraftment in the heart.

PMID- 29215318
TI  - Therapeutic potential of silymarin in chronic unpredictable mild stress induced
      depressive-like behavior in mice.
AB  - Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited
      significant antidepressant-like activity in an acute restraint stress model of
      depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in
      the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The
      present study was undertaken to explore the antidepressant potential of silymarin
      in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in
      mice, and to find out its probable mechanism(s) of action, mainly neurogenesis,
      neuroinflammation, and/or oxidative stress. The mice were subjected to CUMS for
      28 days (4 weeks) and administered with silymarin (100 mg/kg and 200 mg/kg), or
      fluoxetine or vehicle from days 8 to 28 (3 weeks simultaneously). Animals were
      evaluated for behavioral changes, such as anhedonia by sucrose preference test,
      behavioral despair by forced swim test, and exploratory behaviors by an open
      field test. In addition, neurobiochemical alterations, mainly monoamines, 5-HT,
      NE, DA, neurotrophic factor BDNF, and cytokines, IL-6, TNF-alpha, oxidant
      antioxidant parameters by determining the malondialdehyde formation (an index of
      lipid peroxidation process), superoxide dismutase (SOD) and catalase (CAT)
      activity in hippocampus and cerebral cortex along with serum corticosterone were
      investigated. Our findings reveal that mice subjected to CUMS exhibited lower
      sucrose preference, increase immobility time without affecting general locomotion
      of the animals, and reduce BDNF, 5-HT, NE, and DA level, increased serum
      corticosterone, IL-6 and TNF-alpha along with an oxidant-antioxidant imbalance in
      the hippocampus and cerebral cortex. Silymarin significantly reversed the CUMS
      induced changes in the hippocampus and cerebral cortex in mice. Thus, the
      possible mechanism involved in the antidepressant-like activity of silymarin is
      correlated to the alleviation of monoaminergic, neurogenesis (enhancing 5-HT, NE,
      and BDNF levels), and attenuation of inflammatory cytokines system and oxidative
      stress by modulation of corticosterone response, restoration of antioxidant
      defense system in cerebral cortex and hippocampus.

PMID- 29215317
TI  - Novel application and serial evaluation of tissue-engineered portal vein grafts
      in a murine model.
AB  - AIM: Surgical management of pediatric extrahepatic portal vein obstruction
      requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered
      vascular grafts (TEVGs) provide an alternative, but no validated animal models
      using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein
      bypass grafts. MATERIALS & METHODS: TEVGs were implanted as portal vein
      interposition conduits in SCID-beige mice, monitored by ultrasound and micro
      computed tomography, and histologically assessed postmortem at 12 months.
      RESULTS: TEVGs remained patent for 12 months. Histologic analysis demonstrated
      formation of neovessels that resembled native portal veins, with similar content
      of smooth muscle cells, collagen type III and elastin. CONCLUSION: TEVGs are
      feasible portal vein conduits in a murine model. Further preclinical evaluation
      of TEVGs may facilitate pediatric clinical translation.

PMID- 29215319
TI  - Examining the potential preventative effects of minocycline prescribed for acne
      on the incidence of severe mental illnesses: A historical cohort study.
AB  - BACKGROUND: Animal studies suggest that the antibiotic and microglial activation
      inhibitor, minocycline, is likely to have a protective effect against the
      emergence of psychosis but evidence from human studies is lacking. The aim of
      this study is to examine the effects of exposure to minocycline during
      adolescence on the later incidence of severe mental illness (SMI). METHODS: A
      historical cohort study using electronic primary care data was conducted to
      assess the association between exposure to minocycline during adolescence and
      incidence of SMI. The Incidence Rate Ratio (IRR) was measured using Poisson
      regression adjusted for age, gender, time of exposure, socioeconomic deprivation
      status, calendar year and co-medications. RESULTS: Early minocycline prescription
      ( n=13,248) did not affect the incidence of SMI compared with non-prescription of
      minocycline ( n=14,393), regardless of gender or whether or not the data were
      filtered according to a minimum exposure period (minimum period: IRR 0.96; 95% CI
      0.68-1.36; p=0.821; no minimum period: IRR 1.08; 95% CI 0.83-1.42; p=0.566).
      CONCLUSIONS: Exposure to minocycline for acne treatment during adolescence
      appears to have no effect on the incidence of SMI.

PMID- 29215320
TI  - Early Effects of Rhodomyrtone on Membrane Integrity in Methicillin-Resistant
      Staphylococcus aureus.
AB  - Strong evidence of high potency of rhodomyrtone as a promising antibacterial
      agent against pathogenic gram-positive bacteria has been clearly demonstrated in
      our previous work. The aim of this study was to provide insight into early action
      of rhodomyrtone, an acylphloroglucinol, on membrane damage in multidrug-resistant
      methicillin-resistant Staphylococcus aureus (MRSA). Early effects of rhodomyrtone
      on the bacterial membrane integrity were detected in a time-course study. Flow
      cytometry revealed a reduction in green fluorescent emission and increase in
      uptake of propidium iodide in rhodomyrtone-treated bacterial cells in a
      concentration- and time-dependent manner. Disruption of cytoplasmic membrane was
      further monitored by measuring cellular adenosine triphosphate (ATP) and
      potassium ion (K+). Leakage of both ATP and K+ and significant decrease in
      intracellular ATP in MRSA were observed following treatment. Pronounced changes
      in the bacterial ultrastructure and morphology were confirmed by transmission
      electron microscopy and scanning electron microscopy. Bacterial cell disruption,
      holes in cell surface, and bulge formations were noted in rhodomyrtone-treated
      cells. In this study, we provided relevant data to clarify that rhodomyrtone is a
      bacterial cell membrane-damaging agent. A possible early effect of this novel
      compound involves bacterial membrane disruption.

PMID- 29215321
TI  - Mesenchymal endometrial stem/stromal cells for hard tissue engineering: a review
      of in vitro and in vivo evidence.
AB  - Hard tissues including teeth, bone and cartilage have inability or poor capacity
      to self-renew, especially in large defects. Therefore, repair of damages in these
      tissues represents a huge challenge in the medical field today. Hard tissue
      engineering commonly utilizes different stem cell sources as a promising strategy
      for treating bone, cartilages and tooth defects or disorders. Decades ago,
      researchers successfully isolated and identified endometrial mesenchymal
      stem/stromal cells (EnSCs) and discovered their multidifferentiation potential.
      Current studies suggest that EnSCs have significant advantages compared with stem
      cells derived from other tissues. In this review article, we summarize the
      current in vitro and in vivo studies that utilize EnSCs or menstrual blood
      derived stem cells for differentiation to osteoblasts, odontoblasts or
      chondroblasts in an effort to realize the potential of these cells in hard
      tissues regeneration.

PMID- 29215324
TI  - Letter to the Editor.

PMID- 29215322
TI  - Aberrant SIRT6 expression contributes to melanoma growth: Role of the autophagy
      paradox and IGF-AKT signaling.
AB  - Melanoma is among the most life-threatening cancers. The pathogenesis of melanoma
      has not been fully elucidated. Recently, dysregulated macroautophagy/autophagy
      has been found to play a critical but inconsistent role in modulating melanoma
      growth at different stages, with the regulatory mechanism unclear. The histone
      deacetylase SIRT6 (sirtuin 6) is a known autophagy regulator, and its involvement
      in cancer development has been reported. Therefore, we sought to determine the
      role of SIRT6 in melanoma growth and detect its possible link with autophagy in
      the current study. We initially observed that the expression of SIRT6 decreased
      in primary melanoma but increased in metastatic melanoma compared with
      melanocytic nevus. Notably, the expression of SIRT6 was significantly correlated
      with the expression of autophagy biomarkers including MAP1LC3/LC3 and SQSTM1/p62.
      Furthermore, SIRT6 suppressed the growth of primary melanoma but promoted
      metastatic melanoma development in an autophagy-dependent way in vitro. Moreover,
      SIRT6 exerted its regulation on melanoma growth via the IGF-AKT signaling
      pathway, and the intervention of AKT could partly reverse the effects of SIRT6 on
      melanoma growth by regulating autophagy. At last, we determined the effects of
      SIRT6 on melanoma development in vivo. Taken together, our findings demonstrate
      that the bimodal expression of SIRT6 at different melanoma stages plays a
      critical role in regulating melanoma growth through an autophagy-dependent
      manner, which indicates the potential of SIRT6 to be a biomarker and a
      therapeutic target in melanoma.

PMID- 29215325
TI  - DosiKit, a New Portable Immunoassay for Fast External Irradiation Biodosimetry.
AB  - DosiKit is a new field-radiation biodosimetry immunoassay for rapid triage of
      individuals exposed to external total-body irradiation. Here, we report on the
      validation of this immunoassay in human blood cell extracts 0.5 h after in vitro
      exposure to 137Cs gamma rays, using gamma-H2AX analysis. First, calibration
      curves were established for five donors at doses ranging from 0 to 10 Gy and dose
      rates ranging from ~0.8 to ~3 Gy/min. The calibration curves, together with a
      gamma-H2AX peptide scale, enabled the definition of inter-experimental correction
      factors. Using previously calculated correction factors, blind dose estimations
      were performed at 0.5 h postirradiation, and DosiKit performance was compared
      against concomitant dicentric chromosome assay (DCA), the current gold standard
      for external irradiation biodosimetry. A prototype was then assembled and field
      tested. We show that, despite significant inter-individual variations, DosiKit
      can estimate total-body irradiation doses from 0.5 to 10 Gy with a strong linear
      dose-dependent signal and can be used to classify potentially exposed individuals
      into three dose ranges: below 2 Gy, between 2 and 5 Gy and above 5 Gy. The entire
      protocol can be performed in 45 min, from sampling to dose estimation, with a new
      patient triaged every 10 min. While DCA enables precise measurement of doses
      below 5 Gy, it is a long and difficult method. In contrast, DosiKit is a quick
      test that can be performed directly in the field by operational staff with
      minimal training, and is relevant for early field triage and identification of
      individuals most likely to experience acute radiation syndrome. These findings
      suggest that DosiKit and DCA are complementary and should be combined for triage
      in a mass scale event. While the proof-of-concept reported here validates the use
      of DosiKit at 0.5 h postirradiation, further studies are needed to calibrate and
      evaluate the performance of the DosiKit assay at longer times after irradiation.

PMID- 29215326
TI  - The Role of FABP5 in Radiation-Induced Human Skin Fibrosis.
AB  - Radiation-induced skin fibrosis is a detrimental and chronic disorder that occurs
      after radiation exposure. The molecular changes underlying the pathogenesis of
      radiation-induced fibrosis of human skin have not been extensively reported.
      Technical advances in proteomics have enabled exploration of the biomarkers and
      molecular pathogenesis of radiation-induced skin fibrosis, with the potential to
      broaden our understanding of this disease. In this study, we compared protein
      expression in radiation-induced fibrotic human skin and adjacent normal tissues
      using iTRAQ-based proteomics technology. We identified 186 preferentially
      expressed proteins (53 upregulated and 133 downregulated) between radiogenic
      fibrotic and normal skin tissues. The differentially expressed proteins included
      keratins (KRT5, KRT6A, KRT16 and KRT17), caspase-14, fatty acid-binding protein 5
      (FABP5), SLC2A14 and resistin. Through bioinformatic analysis of the proximal
      promoters, common motifs and corresponding transcriptional factors were
      identified that associate with the dysregulated proteins, including PAX5, TBX1,
      CLOCK and AP2D. In particular, FABP5 (2.15-fold increase in fibrotic skin
      tissues), a transporter of hydrophobic fatty acids, was investigated in greater
      detail. Immunohistochemistry confirmed that the protein level of FABP5 was
      increased in fibrotic human skin tissues, especially in the epidermis.
      Overexpression of FABP5 resulted in nuclear translocation of SMAD2 and
      significant activation of the profibrotic TGF-beta signaling pathway in human
      fibroblast WS1 cells. Moreover, exogenous FABP5 (FABP5-EGFP) could be
      incorporated by skin cells and intensify TGF-beta signaling, indicating a
      communication between the microenvironment and skin fibrosis. Taken together, our
      findings illustrate the molecular changes during radiation-induced human skin
      fibrosis and the critical role of FABP5 in activating the TGF-beta signaling
      pathway.

PMID- 29215327
TI  - Factors Modifying the Radon-Related Lung Cancer Risk at Low Exposures and
      Exposure Rates among German Uranium Miners.
AB  - It is still not fully understood whether and how factors such as time, age and
      smoking modify the relationship between lung cancer and radon at low exposures
      and exposure rates. Improved knowledge is necessary for the dose conversion of
      radon in working level month (WLM) into effective dose, as currently discussed by
      the International Commission on Radiological Protection (ICRP). An update of the
      German uranium miner cohort study (n = 58,974 men) with a 10-year extension of
      mortality follow-up (1946-2013) was used to further examine this issue. Internal
      Poisson regression was applied to estimate the excess relative risk (ERR) for
      lung cancer mortality per unit of cumulative radon exposure in WLM with
      exponential time-related effect modifiers. In the full cohort restricted to <100
      WLM the estimated overall ERR/WLM was 0.006 [95% confidence interval (CI): 0.003;
      0.010] based on 1,254 lung cancer deaths and 1,620,190 person-years at risk. Both
      age at and time since exposure turned out to be important modifiers of the
      ERR/WLM and were included in the final model. Here, the ERR/WLM centered on age
      at exposure of 30 years, and 20 years since exposure was 0.016 (95% CI: 0.008;
      0.028). This value decreased statistically significantly by approximately 40% and
      60% for each 10-year increase in age at exposure and time since exposure,
      respectively. The joint effect of smoking and radon exposure was investigated in
      the sub-cohort of miners hired in 1960 or later, which includes data on smoking
      status. The centered ERR/WLM was slightly higher for non/light smokers compared
      to moderate/heavy smokers (0.022 versus 0.013). The current findings provide
      evidence for an increased lung cancer risk at low radon exposures or exposure
      rates that is modified by age and time. The observed risk is lower, but
      statistically compatible to those of other miner studies at low exposures or
      exposure rates. These findings reject an additive- and support a sub- to (supra-)
      multiplicative interaction between smoking and radon.

PMID- 29215328
TI  - A realist evaluation of social prescribing: an exploration into the context and
      mechanisms underpinning a pathway linking primary care with the voluntary sector.
AB  - This article adopts a realist approach to evaluate a social prescribing pilot in
      the areas of Hackney and City in London (United Kingdom). It unpacks the
      contextual factors and mechanisms that influenced the development of this pilot
      for the benefits of GPs, commissioners and practitioners, and reflects on the
      realist approach to evaluation as a tool for the evaluation of health
      interventions. Primary care faces considerable challenges including the increase
      in long-term conditions, GP consultation rates, and widening health inequalities.
      With its emphasis on linking primary care to non-clinical community services via
      a social prescribing coordinator (SPC), some models of social prescribing could
      contribute to reduce the burden on primary care, tackle health inequalities and
      encourage people to make greater use of non-clinical forms of support. This
      realist analysis was based on qualitative interviews with users, commissioners, a
      GP survey, focus groups and learning events to explore stakeholders' experience.
      To enable a detailed analysis, we adapted the realist approach by subdividing the
      social prescribing pathway into stages, each with contextual factors, mechanisms
      and outcomes. SPCs were pivotal to the effective functioning of the social
      prescribing service and responsible for the activation and initial beneficial
      impact on users. Although social prescribing shows significant potential for the
      benefit of patients and primary care, several challenges need to be considered
      and overcome, including 'buy in' from some GPs, branding, and funding for the
      third sector in a context where social care cuts are severely affecting the
      delivery of health care. With its emphasis on context and mechanisms, the realist
      evaluation approach is useful in understanding how to identify and improve health
      interventions, and analyse in greater detail the contribution of different
      stakeholders. As the SPC is central to social prescribing, more needs to be done
      to understand their role conceptually and practically.

PMID- 29215330
TI  - Quantifying Hospital-Acquired Carriage of Extended-Spectrum Beta-Lactamase
      Producing Enterobacteriaceae Among Patients in Dutch Hospitals.
AB  - BACKGROUND Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E)
      are emerging worldwide. Contact precautions are recommended for known ESBL-E
      carriers to control the spread of ESBL-E within hospitals. OBJECTIVE This study
      quantified the acquisition of ESBL-E rectal carriage among patients in Dutch
      hospitals, given the application of contact precautions. METHODS Data were used
      from 2 cluster-randomized studies on isolation strategies for ESBL-E: (1) the SoM
      study, performed in 14 Dutch hospitals from 2011 through 2014 and (2) the R
      GNOSIS study, for which data were limited to those collected in a Dutch hospital
      in 2014. Perianal cultures were obtained, either during ward-based prevalence
      surveys (SoM), or at admission and twice weekly thereafter (R-GNOSIS). In both
      studies, contact precautions were applied to all known ESBL-E carriers. Estimates
      for acquisition of ESBL-E were based on the results of admission and discharge
      cultures from patients hospitalized for more than 2 days (both studies) and a
      Markov chain Monte Carlo (MCMC) model, applied to all patients hospitalized (R
      GNOSIS). RESULTS The absolute risk of acquisition of ESBL-E rectal carriage
      ranged from 2.4% to 2.9% with an ESBL-E acquisition rate of 2.8 to 3.8
      acquisitions per 1,000 patient days. In addition, 28% of acquisitions were
      attributable to patient-dependent transmission, and the per-admission
      reproduction number was 0.06. CONCLUSIONS The low ESBL-E acquisition rate in this
      study demonstrates that it is possible to control the nosocomial transmission of
      ESBL in a low-endemic, non-ICU setting where Escherichia coli is the most
      prevalent ESBL-E and standard and contact precautions are applied for known ESBL
      E carriers. TRIAL REGISTRATION Nederlands Trialregister, NTR2799,
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2799; ISRCTN Registry,
      ISRCTN57648070, http://www.isrctn.com/ISRCTN57648070 Infect Control Hosp
      Epidemiol 2018;39:32-39.

PMID- 29215329
TI  - Chemotherapeutics of visceral leishmaniasis: present and future developments.
AB  - Treatment of Visceral Leishmaniasis (VL), a neglected tropical disease, is very
      challenging with few treatment options. Long duration of treatment and drug
      toxicity further limit the target of achieving VL elimination. Chemotherapy
      remains the treatment of choice. Single dose of liposomal amphotericin B (LAmB)
      and multidrug therapy (LAmB + miltefosine, LAmB + paromomycin (PM), or
      miltefosine + PM) are recommended treatment regimen for treatment of VL in Indian
      sub-continent. Combination therapy of pentavalent antimonials (Sbv) and PM in
      East Africa and LAmB in the Mediterranean region/South America remains the
      treatment of choice. Various drugs having anti-leishmania properties are in
      preclinical phase and need further development. An effective treatment and
      secondary prophylaxis of HIV-VL co-infection should be developed to decrease
      treatment failure and drug resistance.

PMID- 29215331
TI  - A comparative transcriptomic analysis of replicating and dormant liver stages of
      the relapsing malaria parasite Plasmodium cynomolgi.
AB  - Plasmodium liver hypnozoites, which cause disease relapse, are widely considered
      to be the last barrier towards malaria eradication. The biology of this quiescent
      form of the parasite is poorly understood which hinders drug discovery. We report
      a comparative transcriptomic dataset of replicating liver schizonts and dormant
      hypnozoites of the relapsing parasite Plasmodium cynomolgi. Hypnozoites express
      only 34% of Plasmodium physiological pathways, while 91% are expressed in
      replicating schizonts. Few known malaria drug targets are expressed in quiescent
      parasites, but pathways involved in microbial dormancy, maintenance of genome
      integrity and ATP homeostasis were robustly expressed. Several transcripts
      encoding heavy metal transporters were expressed in hypnozoites and the copper
      chelator neocuproine was cidal to all liver stage parasites. This transcriptomic
      dataset is a valuable resource for the discovery of vaccines and effective
      treatments to combat vivax malaria.

PMID- 29215333
TI  - Erratum: "New Blood: The Promise of Environmental Health Citizen Science
      Projects".
AB  - [This corrects the article DOI: 10.1289/EHP2484.].

PMID- 29215334
TI  - Key Developments in Translational Neuroscience: an Update.

PMID- 29215332
TI  - Nodal patterning without Lefty inhibitory feedback is functional but fragile.
AB  - Developmental signaling pathways often activate their own inhibitors. Such
      inhibitory feedback has been suggested to restrict the spatial and temporal
      extent of signaling or mitigate signaling fluctuations, but these models are
      difficult to rigorously test. Here, we determine whether the ability of the
      mesendoderm inducer Nodal to activate its inhibitor Lefty is required for
      development. We find that zebrafish lefty mutants exhibit excess Nodal signaling
      and increased specification of mesendoderm, resulting in embryonic lethality.
      Strikingly, development can be fully restored without feedback: Lethal patterning
      defects in lefty mutants can be rescued by ectopic expression of lefty far from
      its normal expression domain or by spatially and temporally uniform exposure to a
      Nodal inhibitor drug. While drug-treated mutants are less tolerant of mild
      perturbations to Nodal signaling levels than wild type embryos, they can develop
      into healthy adults. These results indicate that patterning without inhibitory
      feedback is functional but fragile.

PMID- 29215335
TI  - Previous Antibiotic Exposure and Antimicrobial Resistance Patterns of
      Acinetobacter spp. and Pseudomonas aeruginosa Isolated from Patients with
      Nosocomial Infections.
AB  - BACKGROUND: The alarming spread of antibiotic-resistant bacteria causing
      healthcare-associated infections has been extensively reported in recent medical
      literature. AIMS: To compare trends in antimicrobial consumption and development
      of resistance among isolates of Acinetobacter spp. and Pseudomonas aeruginosa
      that cause hospital infections. STUDY DESIGN: Cross-sectional study. METHODS: A
      study was conducted in a tertiary healthcare institution in central Serbia,
      during the 7-year period between January 2009 and December 2015. The incidence
      rate of infections caused by Acinetobacter or Pseudomonas, as well as their
      resistance density to commonly used antibiotics, were calculated. Utilization of
      antibiotics was expressed as the number of defined daily doses per 1000 patient
      days. RESULTS: A statistically significant increase in resistance density in 2015
      compared to the first year of observation was noted for Acinetobacter, but not
      for Pseudomonas, to third-generation cephalosporins (p=0.008), aminoglycosides
      (p=0.005), carbapenems (p=0.003), piperacillin/tazobactam (p=0.025),
      ampicillin/sulbactam (p=0.009) and tigecycline (p=0.048). CONCLUSION: Our study
      showed that there is an association between the resistance density of
      Acinetobacter spp. and utilization of carbapenems, tigecycline and
      aminoglycosides. A multifaceted intervention is needed to decrease the incidence
      rate of Acinetobacter and Pseudomonas hospital infections, as well as their
      resistance density to available antibiotics.

PMID- 29215336
TI  - Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3
      Protein Levels in Human-Derived Liver (HepG2) Cells.
AB  - BACKGROUND: Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant
      and anti-atherosclerotic structural high-density lipoprotein proteins that are
      mainly synthesized by the liver. No study has ever been performed to specifically
      examine the effects of caffeine on paraoxonase enzymes and on liver
      apolipoprotein A-1 protein levels. AIMS: To investigate the dose-dependent
      effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3
      protein levels. STUDY DESIGN: In vitro experimental study. METHODS: HepG2 cells
      were incubated with 0 (control), 10, 50 and 200 MUM of caffeine for 24 hours.
      Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3
      protein levels were measured by western blotting. RESULTS: We observed a
      significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in
      the cells incubated with 50 uM of caffeine and a significant increase on
      paraoxonase-1 protein level in the cells incubated with 200 uM of caffeine.
      CONCLUSION: Our study showed that caffeine does not change paraoxonase-3 protein
      level, but the higher doses used in our study do cause an increase in both
      apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

PMID- 29215337
TI  - Adherence to Nucleoside/Nucleotide Analogue Treatment in Patients with Chronic
      Hepatitis B.
AB  - BACKGROUND: Adherence to medication is an important aspect of preventing drug
      resistance and treatment failure in patients receiving nucleos(t)ide analogues
      for chronic hepatitis B. AIMS: To assess adherence to nucleoside/nucleotide
      analogues in chronic hepatitis B treatment and to determine factors associated
      with non-adherence. STUDY DESIGN: Cross-sectional study. METHODS: The study
      enrolled 85 chronic hepatitis B patients who had been receiving
      nucleoside/nucleotide analogues for >=3 months. A questionnaire was completed by
      patients themselves, and adherence was evaluated based on patients' self
      reporting. The use of at least 95% of the drugs in the previous month was
      considered as adequate adherence. RESULTS: Adherence was adequate in 82.4% of
      patients. Female gender (p=0.003), unemployment (p=0.041) and lower monthly
      family income (p=0.001) were related to lower adherence. Better adherence was
      significantly linked to adequate basic knowledge regarding chronic hepatitis B
      (p=0.049), longer treatment duration than 12 months (p<0.001), previous use of
      other medications for chronic hepatitis B (p=0.014) and regular follow-up by the
      same physician (p<0.001). CONCLUSION: Counselling patients about their disease
      state and the consequences of non-adherence is an important intervention for
      enhancing adherence. Naive patients should be followed up more frequently to
      reinforce adherence.

PMID- 29215339
TI  - The Association of Congenital Urethral Duplication and Double Megalourethra.
AB  - BACKGROUND: Urethral duplication and megalourethra are rare urethral anomalies.
      However, the concomitance of urethral duplication and double megalourethra has
      not been reported previously. CASE REPORT: A newborn was presented with penile
      swelling during voiding. Physical examination revealed a retractable foreskin and
      two external meatus of a double urethra. Retrograde urethrography demonstrated
      two complete megalourethras. Urethro-urethrostomy and urethroplasty were
      performed when the patient was 10 months old. The patient was followed up for one
      year without any urinary problems and has good cosmetics and urinary continence.
      CONCLUSION: The concomitance of these two rare anomalies and more importantly its
      surgical treatment makes this case report unique and valuable.

PMID- 29215338
TI  - Evaluation of Antimicrobial Durability and Anti-Biofilm Effects in Urinary
      Catheters Against Enterococcus faecalis Clinical Isolates and Reference Strains.
AB  - BACKGROUND: Enterococcus faecalis, Escherichia coli, Staphylococcus epidermidis,
      Pseudomonas aeruginosa and Candida albicans biofilms are major causes of catheter
      associated urinary tract infections. Antimicrobial-coated or impregnated urinary
      catheters are seen as a possible way to prevent these infections. AIMS: To
      determine the biofilm-forming ability of 89 E. faecalis isolates from urinary
      tract infections and to compare several urinary catheters for antimicrobial
      durability and the inhibitory effects on biofilm formation of different
      laboratory strains and clinical isolates of E. faecalis. STUDY DESIGN: In vitro
      experimental study. METHODS: The biofilm forming ability of E. faecalis isolates
      was determined by the crystal violet staining and plate counting methods. For
      comparison of urinary catheters, biofilms of 45 E. faecalis isolates from the
      catheter samples of hospitalized patients and five laboratory strains of E. coli
      ATCC25922, S. epidermidis ATCC35984, P. aeruginosa ATCC27853, E. faecalis
      ATCC29212 and C. albicans ATCC90028 were formed on the catheters in 24-well
      tissue culture plates. Scanning electron microscopy analysis was performed to
      observe biofilms. RESULTS: All 89 E. faecalis isolates were found to be biofilm
      positive. Nitrofurazone-impregnated catheters significantly reduced the cell
      counts of E. faecalis isolates and completely inhibited the formation of P.
      aeruginosa and S. epidermidis biofilms compared with the others. Regarding
      reduction of biofilm cell counts, a hydrophilic-coated catheter was more
      effective against P. aeruginosa, whereas a silver-coated catheter was found to be
      more effective against S. epidermidis. The nitrofurazone-impregnated catheter had
      the best antimicrobial durability. CONCLUSION: Urine isolates of E. faecalis had
      considerable ability with respect to biofilm formation. The nitrofurazone
      impregnated catheter was the most effective against all tested bacteria; however,
      the effect of a hydrophilic or silver-coated catheter depends on the species
      present in it.

PMID- 29215340
TI  - A Report of Brugada Syndrome Presenting with Cardiac Arrest Triggered by
      Verapamil Intoxication.
AB  - BACKGROUND: Brugada syndrome is a disease characterized by a specific
      electrocardiographic pattern and an increased risk of sudden cardiac death. We
      present this case with the updated literature to emphasise the need to consider
      the diagnosis of Brugada syndrome in patients admitted to the emergency ward with
      sudden cardiac arrest. CASE REPORT: A 16-year-old female patient was admitted to
      the emergency ward with complaints of weakness and abdominal pain, and she had
      four cardiac arrests during her evaluation period. She was referred to our clinic
      for permanent pacemaker implantation. She was on a temporary pace maker after
      having had C-reactive protein. Her physical exam was normal except for
      bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were
      performed by another institution, revealed minimal pleural effusion and nothing
      else of significance. Blood and peritoneal fluid samples were sterile.
      Echocardiographic exam and cardiac enzymes were also in the normal ranges.
      Electrocardiographic showed incomplete right branch block in leads V1 and V2. An
      ajmaline test revealed specific electrocardiographic findings of the type I
      Brugada pattern. We proposed implanting an implantable cardioverter defibrillator
      to the patient as there were positive findings on the ajmaline test as well as a
      history of sudden cardiac arrest. After this treatment proposal, the patient's
      family admitted that she had taken a high dose of verapamil and thus, the
      encountered bradycardia was associated with verapamil overuse. The ajmaline test
      was repeated as it was contemplated that the previous positive ajmaline test had
      been associated with verapamil overuse. Implantable cardioverter defibrillator
      implantation was proposed again as there was a history of sudden cardiac arrest;
      however, the family did not consent to implantable cardioverter defibrillator,
      and the patient was discharged and followed up. CONCLUSION: Brugada syndrome
      should be considered for patients who are admitted to the emergency ward with
      sudden cardiac arrest though surface electrocardiographic is normal. If there is
      a suspicion of Brugada syndrome, repeated electrocardiographic should be
      performed on different occasions. Diagnosis can be clarified by upper costal
      electrocardiographic or by administering Na channel blockers during
      electrocardiographic performance.

PMID- 29215341
TI  - A Rare Complication of Phenytoin Infusion in Newborn: Purple Glove Syndrome.

PMID- 29215342
TI  - Pediatric Intranasal Lobular Capillary Hemangioma: A Rare Clinical Entity.

PMID- 29215343
TI  - Bladder Preservation with Primary Closure in an Adolescent Girl with Bladder
      Exstrophy.

PMID- 29215344
TI  - A New Laparoscopic Manoeuvre in Median Arcuate Ligament Syndrome.

PMID- 29215345
TI  - h-BN-layer-induced chiral decomposition in the electronic properties of
      multilayer graphene.
AB  - We discuss the chiral decomposition of non-symmetric stacking structures. It is
      shown that the low-energy electronic structure of a Bernal stacked graphene
      multilayer deposited on h-BN consists of chiral pseudospin doublets. N-layer
      graphene stacks on the h-BN layer have N/2 effective bilayer graphene systems and
      one effective h-BN layer if N is even or [Formula: see text] effective graphene
      bilayers plus one graphene monolayer modified by an h-BN layer if N is odd. We
      present the decomposition procedure and derive the recurrence relations for the
      effective parameters characterizing the chiral subsystems. In this case, the
      effective parameters consist of interlayer couplings and on-site potentials in
      contrast to pure graphene multilayer systems where only interlayer couplings are
      modified. We apply this procedure to discuss the Klein tunnelling phenomena and
      quantitatively compare the results with pure graphene multilayer systems.

PMID- 29215346
TI  - Metal oxide multilayer hard mask system for 3D nanofabrication.
AB  - We demonstrate the preparation and exploitation of multilayer metal oxide hard
      masks for lithography and 3D nanofabrication. Atomic layer deposition (ALD) and
      focused ion beam (FIB) technologies are applied for mask deposition and mask
      patterning, respectively. A combination of ALD and FIB was used and a patterning
      procedure was developed to avoid the ion beam defects commonly met when using FIB
      alone for microfabrication. ALD grown Al2O3/Ta2O5/Al2O3 thin film stacks were FIB
      milled with 30 keV gallium ions and chemically etched in 5% tetramethylammonium
      hydroxide at 50  degrees C. With metal evaporation, multilayers consisting of
      amorphous oxides Al2O3 and Ta2O5 can be tailored for use in 2D lift-off
      processing, in preparation of embedded sub-100 nm metal lines and for multilevel
      electrical contacts. Good pattern transfer was achieved by lift-off process from
      the 2D hard mask for micro- and nano-scaled fabrication. As a demonstration of
      the applicability of this method to 3D structures, self-supporting 3D Ta2O5 masks
      were made from a film stack on gold particles. Finally, thin film resistors were
      fabricated by utilizing controlled stiction of suspended Ta2O5 structures.

PMID- 29215347
TI  - Locally preserved alpha  ->  beta phase transition in natural radiation-damaged
      titanite (CaTiSiO5): evidence from laser-induced photoluminescence and dielectric
      measurements.
AB  - In situ temperature-dependent laser-induced photoluminescence and dielectric
      measurements provide new evidence for the local occurrence of the alpha  ->  beta
      phase transition near 500 K in the preserved crystalline parts of natural
      radiation-damaged titanite (sample E2335 with ~24% amorphous fraction, containing
      Fe and Al impurities). Photoluminescence spectroscopic measurements show an
      anomaly in the vicinity of 500 K. The temperature-dependent evolution of the real
      part of the electrical conductivity (sigma) and the real (epsilon') and the
      imaginary (epsilon") part of the complex dielectric permittivity (epsilon *) of
      titanite have been measured at various AC frequencies (~1.2-96.8 kHz). Despite
      the masking and smearing effect of impurities and defects, the temperature
      dependent behaviour of epsilon' and epsilon" around the transition temperature of
      the investigated natural titanite E2335 shows a remarkable similarity to that of
      the synthetic end-member material (see Zhang et al (1995 Phys. Chem. Miner. 22 41
      9)). This study indicates the suitability of photoluminescence and impedance
      spectroscopy for the detection of phase transitions, even in heavily disordered
      systems.

PMID- 29215348
TI  - Field emission behavior of boron nitride nanotubes.
AB  - The field emission properties of boron nitride nanotube (BNNT) field emitters
      according to vacuum pressure were demonstrated. During the short-term emission
      operation, the field emission behaviors were almost similar, regardless of the
      vacuum pressure, even though the turn-on electric field of the BNNT field emitter
      was slightly increased as the vacuum pressure increased. On the other hand,
      during the long-term emission operation, both the degradation and fluctuations of
      the emission current of the BNNT field emitters were dramatically increased as
      the vacuum pressure increased. The degradation of field emission properties of
      the BNNT emitters according to vacuum pressure is mainly attributed to the ion
      bombardment effect, rather than the oxidation effect. The field emission behavior
      under Ar ambient also strongly demonstrates that the degradation and the
      fluctuation of the emission current are largely dependent on the ion bombardment
      effect.

PMID- 29215349
TI  - Spatiotemporal variation of bacterial water quality and the relationship with
      pasture land cover.
AB  - Pathogens are a major cause of water quality impairment and public health concern
      world-wide. In the United States, each state is tasked with developing water
      quality standards (WQS) to protect the designated use(s) of waterbodies. Several
      streams in the Illinois River Watershed in northwest Arkansas are currently
      listed as impaired due to elevated levels of pathogens. Our objective was to
      evaluate Escherichia coli (E. coli) numbers at 29 stream sites, compare these
      numbers to the applicable WQS, and investigate the relationship between E. coli
      numbers and land cover variables. E. coli numbers in samples collected at most
      sites were within allowable limits, although there were several instances of
      violations of the WQS. Violations were variable from year to year at some sites,
      and elevated levels of E. coli were spatially localized during baseflow.
      Violations also were positively related to pasture land cover in the drainage
      area, and particularly within the riparian buffer area. This relationship was non
      linear, or threshold based, where there was a significant increase in the mean E.
      coli exceedances when riparian pasture land cover was greater than approximately
      50%. These results can be used to identify specific stream reaches where E. coli
      numbers might be elevated and the implementation of best management practices can
      be geographically targeted.

PMID- 29215350
TI  - Prevalence and types of Campylobacter on poultry farms and in their direct
      environment.
AB  - To study whether broiler and layer farms contribute to the environmental
      Campylobacter load, environmental matrices at or close to farms, and caecal
      material from chickens, were examined. Similarity between Campylobacter from
      poultry and environment was tested based on species identification and Multilocus
      Sequence Typing. Campylobacter prevalence in caecal samples was 97% at layer
      farms (n = 5), and 93% at broiler farms with Campylobacter-positive flocks (n =
      2/3). Campylobacter prevalence in environmental samples was 24% at layer farms,
      and 29% at broiler farms with Campylobacter-positive flocks. Campylobacter was
      detected in soil and surface water, not in dust and flies. Campylobacter
      prevalence in adjacent and remote surface waters was not significantly (P > 0.1)
      different. Detected species were C. coli (52%), C. jejuni (40%) and C. lari (7%)
      in layers, and C. jejuni (100%) in broilers. Identical sequence types (STs) were
      detected in caecal material and soil. A deviating species distribution in surface
      water adjacent to farms indicated a high background level of environmental
      Campylobacter. STs from layer farms were completely deviant from surface water
      STs. The occasional detection of identical STs in broilers, wastewater at broiler
      farms and surface water in the farm environment suggested a possible contribution
      of broiler farms to the aquatic environmental Campylobacter load.

PMID- 29215351
TI  - Moringa oleifera functionalised sand - reuse with non-ionic surfactant dodecyl
      glucoside.
AB  - Moringa oleifera seeds are well known for their ability to cause flocculation in
      turbid water and facilitate bacterial inhibition. These effects are due to the
      cationic polypeptide MO2.1, which affects the surface charge of suspended
      particles and causes lysis of bacterial cells. However, the attachment of
      bacteria to MO2.1 prevents further bacterial attachment, reducing the
      effectiveness of the seeds. This research investigated the effect of surfactants
      on functionality and reuse of Moringa seeds to develop a sustainable water
      treatment technique. The seed extracts (MO2.1) were used with a functionalised
      sand system, and the sands were exposed to commercially available (ionic and non
      ionic) surfactants, dodecyl glucoside and sodium dodecyl sulfate. Artificially
      polluted water contaminated with Escherichia coli was used to evaluate the
      efficiency of the system. The non-ionic surfactant was found to be effective at
      separating E. coli from the functionalised sand without the detachment of the
      MO2.1 and subsequent loss of the system efficiency. This was successfully
      repeated four times. The results demonstrated a sustainable, reusable technique
      to inhibit bacterial contamination in water.

PMID- 29215352
TI  - Emergent contaminants in the wastewater effluents of two highly populated
      tropical cities.
AB  - Exposure to the anthropogenic chemicals known as endocrine disrupting compounds
      (EDCs) may result in negative biological effects. Low levels of EDCs in the
      environment aggravate the problem as exposure is constant. Urban areas
      concentrate pollution as greater volumes are released from human activities.
      Water for public supply is particularly vulnerable as the sewage treatment
      facilities may not eliminate EDCs. The goal was to assess estrogenicity and
      effectiveness of removal of phthalates in primary and tertiary wastewater
      treatment facilities in urban cities in the tropical island of Puerto Rico. A
      yeast bioassay used to measure estrogenicity showed higher removal with tertiary
      treatment. However, results in the picomolar range suggest low doses of
      estrogenic compounds were being released to receiving waters. For the phthalates,
      solid phase extraction and gas chromatography-mass spectrometry analyses revealed
      removals ranging from 42.9% to 92.4% with tertiary treatment. More than 90%
      removal was achieved for benzylbutyl phthalate, dibutyl phthalate and bis-2
      ethylhexyl phthalate. However, concentrations ranging from 0.86 to 1.29 ppm for
      the phthalates in the outflow were detected even at the tertiary waste water
      treatment plant effluent implying failure of EDC removal. These results can
      assist managers in evaluating pollution control technologies to ameliorate the
      impacts of EDCs in the tropics.

PMID- 29215353
TI  - Heterotrophic monitoring at a drinking water treatment plant by matrix-assisted
      laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry after
      different drinking water treatments.
AB  - The aim of this work was to assess the suitability of matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for routine
      heterotrophic monitoring in a drinking water treatment plant. Water samples were
      collected from raw surface water and after different treatments during two
      campaigns over a 1-year period. Heterotrophic bacteria were studied and isolates
      were identified by MALDI-TOF MS. Moreover, the diversity index and the
      coefficient of population similarity were also calculated using biochemical
      fingerprinting of the populations studied. MALDI-TOF MS enabled us to
      characterize and detect changes in the bacterial community composition throughout
      the water treatment plant. Raw water showed a large and diverse population which
      was slightly modified after initial treatment steps (sand filtration and
      ultrafiltration). Reverse osmosis had a significant impact on the microbial
      diversity, while the final chlorination step produced a shift in the composition
      of the bacterial community. Although MALDI-TOF MS could not identify all the
      isolates since the available MALDI-TOF MS database does not cover all the
      bacterial diversity in water, this technique could be used to monitor bacterial
      changes in drinking water treatment plants by creating a specific protein profile
      database for tracking purposes.

PMID- 29215354
TI  - Associations between extreme precipitation and acute gastro-intestinal illness
      due to cryptosporidiosis and giardiasis in an urban Canadian drinking water
      system (1997-2009).
AB  - Drinking water related infections are expected to increase in the future due to
      climate change. Understanding the current links between these infections and
      environmental factors is vital to understand and reduce the future burden of
      illness. We investigated the relationship between weekly reported
      cryptosporidiosis and giardiasis (n = 7,422), extreme precipitation (>90th
      percentile), drinking water turbidity, and preceding dry periods in a drinking
      water system located in greater Vancouver, British Columbia, Canada (1997-2009)
      using distributed lag non-linear Poisson regression models adjusted for
      seasonality, secular trend, and the effect of holidays on reporting. We found a
      significant increase in cryptosporidiosis and giardiasis 4-6 weeks after extreme
      precipitation. The effect was greater following a dry period. Similarly, extreme
      precipitation led to significantly increased turbidity only after prolonged dry
      periods. Our results suggest that the risk of cryptosporidiosis and giardiasis
      increases with extreme precipitation, and that the effects are more pronounced
      after a prolonged dry period. Given that extreme precipitation events are
      expected to increase with climate change, it is important to further understand
      the risks from these events, develop planning tools, and build resilience to
      these future risks.

PMID- 29215355
TI  - Quantitative microbial risk assessment to estimate the health risk from exposure
      to noroviruses in polluted surface water in South Africa.
AB  - This study assessed the risks posed by noroviruses (NoVs) in surface water used
      for drinking, domestic, and recreational purposes in South Africa (SA), using a
      quantitative microbial risk assessment (QMRA) methodology that took a
      probabilistic approach coupling an exposure assessment with four dose-response
      models to account for uncertainty. Water samples from three rivers were found to
      be contaminated with NoV GI (80-1,900 gc/L) and GII (420-9,760 gc/L) leading to
      risk estimates that were lower for GI than GII. The volume of water consumed and
      the probabilities of infection were lower for domestic (2.91 * 10-8 to 5.19 * 10
      1) than drinking water exposures (1.04 * 10-5 to 7.24 * 10-1). The annual
      probabilities of illness varied depending on the type of recreational water
      exposure with boating (3.91 * 10-6 to 5.43 * 10-1) and swimming (6.20 * 10-6 to
      6.42 * 10-1) being slightly greater than playing next to/in the river (5.30 * 10
      7 to 5.48 * 10-1). The QMRA was sensitive to the choice of dose-response model.
      The risk of NoV infection or illness from contaminated surface water is extremely
      high in SA, especially for lower socioeconomic individuals, but is similar to
      reported risks from limited international studies.

PMID- 29215356
TI  - The presence of biofilm forming microorganisms on hydrotherapy equipment and
      facilities.
AB  - Hydrotherapy equipment provides a perfect environment for the formation and
      growth of microbial biofilms. Biofilms may reduce the microbiological cleanliness
      of hydrotherapy equipment and harbour opportunistic pathogens and pathogenic
      bacteria. The aims of this study were to investigate the ability of
      microorganisms that colonize hydrotherapy equipment to form biofilms, and to
      assess the influence of temperature and nutrients on the rate of biofilm
      formation. Surface swab samples were collected from the whirlpool baths,
      inhalation equipment and submerged surfaces of a brine pool at the spa center in
      Ciechocinek, Poland. We isolated and identified microorganisms from the swab
      samples and measured their ability to form biofilms. Biofilm formation was
      observed at a range of temperatures, in both nutrient-deficient and nutrient-rich
      environments. We isolated and identified microorganisms which are known to form
      biofilms on medical devices (e.g. Stenotrophomonas maltophilia). All isolates
      were classified as opportunistic pathogens, which can cause infections in humans
      with weakened immunity systems. All isolates showed the ability to form biofilms
      in the laboratory conditions. The potential for biofilm formation was higher in
      the presence of added nutrients. In addition, the hydrolytic activity of the
      biofilm was connected with the presence of nutrients.

PMID- 29215357
TI  - New technique for direct fluoroimmunomagnetic detection of rotavirus in water
      samples.
AB  - A new rapid, sensitive and selective method for rotavirus detection in water
      samples is described in this paper. Amino pink magnetic microparticles were
      functionalized with monoclonal antibodies and used to capture, concentrate,
      separate and detect infectious rotavirus particles in distilled and drinking
      water samples. The fluorescence of the microparticles was used to determine the
      presumptive presence of rotaviruses by using confocal microscopy. Atomic force
      microscopy and transmission electron microscopy were used to confirm the presence
      of the anti-rotavirus antibodies attached to the surface of the magnetic
      microparticles as well as that of viruses attached through the antibody. In
      addition, RNA extraction, quantification and amplification were carried out to
      validate the microscopic observations. The selectivity of the microparticles was
      tested in a sample containing a mix of enteric viruses. It was concluded that
      functionalizing fluoromagnetic microparticles with anti-rotavirus monoclonal
      antibodies constituted a fast, simple and reliable technique for detecting as low
      as 10 Rotavirus particles in 1 L of artificial or real water in just 2 hours.

PMID- 29215358
TI  - Biofilm forming ability of Sphingomonas paucimobilis isolated from community
      drinking water systems on plumbing materials used in water distribution.
AB  - Sphingomonas paucimobilis, an oligotroph, is well recognized for its potential
      for biofilm formation. The present study explored the biofilm forming ability of
      a strain isolated from municipal drinking water on plumbing materials. The
      intensity of biofilm formation of this strain on different plumbing materials was
      examined by using 1 * 1 cm2 pieces of six different pipe materials, i.e.
      polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), aluminium (Al),
      copper (Cu) and rubber (R) and observing by staining with the chemical
      chromophore, Calcofluor. To understand whether biofilm formation occurs under
      flow through conditions, a laboratory-scale simulated distribution system,
      comprised of the above materials was fabricated. Biofilm samples were collected
      from the designed system at different biofilm ages (10, 40 and 90 hours old) and
      enumerated. The results indicated that the biofilm formation occurred on all
      plumbing materials with Cu and R as exceptions. The intensity of biofilm
      formation was found to be maximum on PVC followed by PP and PE. We also
      demonstrated the chemical chromophore (Calcofluor) successfully for rapid and
      easy visual detection of biofilms, validated by scanning electron microscope
      (SEM) analysis of the plumbing materials. Chlorination has little effect in
      preventing biofilm development.

PMID- 29215359
TI  - Optimization of operational variables and kinetic modeling for photocatalytic
      removal of Direct Blue 14 from aqueous media by ZnS nanoparticles.
AB  - Zinc sulfide nanoparticles (ZnS-NPs) were synthesized via a simple and facile co
      precipitation method and were characterized by X-ray diffraction (XRD), field
      emission scanning electron microscopy (FE-SEM) and diffuse reflectance
      spectroscopy (DRS). Photocatalytic activity of synthesized nanoparticles was
      evaluated in removal of double azo dye Direct Blue 14 (DB14) from aqueous media.
      Optimization of photocatalytic removal of DB14 was studied using response surface
      methodology (RSM). Based on the results, DB14 removal efficiency increased with
      increasing intensity and duration of UV light irradiation, whereas the higher pH
      and higher initial dye concentration were unfavorable. Under optimum conditions
      (initial DB14 concentration =10 mg L-1, ZnS-NPs amount = 0.7 g L-1, pH = 3.5, UV
      light intensity =16 W m-2, and irradiation time = 48 min), dye removal efficiency
      reached up to 88.26%. In continuation of our researches, non-linear regression
      analysis was used to development a kinetics model based on the Langmuir
      Hinshelwood model and an empirical equation was obtained for estimation of
      apparent pseudo-first-order rate constant (kap) as a function of the operational
      variables. Findings indicated a high similarity was between the model prediction
      and experimental results.

PMID- 29215360
TI  - Viruses in the environment - presence and diversity of bacteriophage and enteric
      virus populations in the Umhlangane River, Durban, South Africa.
AB  - Due to the continued persistence of waterborne viral-associated infections, the
      presence of enteric viruses is a concern. Notwithstanding the health
      implications, viral diversity and abundance is an indicator of water quality
      declination in the environment. The aim of this study was to evaluate the
      presence of viruses (bacteriophage and enteric viruses) in a highly polluted,
      anthropogenic-influenced river system over a 6-month period at five sampling
      points. Cytopathic-based tissue culture assays revealed that the isolated viruses
      were infectious when tested on Hep-G2, HEK293 and Vero cells. While transmission
      electron microscopy (TEM) revealed that the majority of the viruses were
      bacteriophages, a number of presumptive enteric virus families were visualized,
      some of which include Picornaviridae, Adenoviridae, Polyomaviridae and
      Reoviridae. Finally, primer specific nested polymerase chain reaction (nested
      PCR)/reverse transcription-polymerase chain reaction (RT-PCR) coupled with BLAST
      analysis identified human adenovirus, polyomavirus and hepatitis A and C virus
      genomes in river water samples. Taken together, the complexity of both
      bacteriophage and enteric virus populations in the river has potential health
      implications. Finally, a systematic integrated risk assessment and management
      plan to identify and minimize sources of faecal contamination is the most
      effective way of ensuring water safety and should be established in all future
      guidelines.

PMID- 29215361
TI  - Identification of antibiotics in wastewater: current state of extraction protocol
      and future perspectives.
AB  - The release and occurrence of antibiotics in the aquatic environment has
      generated increased attention in the past few decades. The residual antibiotic in
      wastewater is important in the selection for antimicrobial resistance among
      microorganisms and the possibility of forming toxic derivatives. This review
      presents an assessment of the advancement in methods for extraction of
      antibiotics with solid phase extraction and liquid-liquid extraction methods
      applied in different aquatic environmental media. These advanced methods do
      enhance specificity, and also exhibit high accuracy and recovery. The aim of this
      review is to assess the pros and cons of the methods of extraction towards
      identification of quinolones and sulphonamides as examples of relevant
      antibiotics in wastewater. The challenges associated with the improvements are
      also examined with a view of providing potential perspectives for better
      extraction and identification protocols in the near future. From the context of
      this review, magnetic molecular imprinted polymer is superior over the remaining
      extraction methods (with the availability of commercial templates and monomers),
      is based on less cumbersome extraction procedures, uses less solvent and has the
      advantage of its reusable magnetic phase.

PMID- 29215362
TI  - The switch to refillable bottled water in Indonesia: a serious health risk.
AB  - In recent years, the consumption of refillable bottled water has increased
      considerably in emerging countries. However, the quality of this water is often
      questionable, as authorities lack the capacity to properly check refilling
      depots. Given that refillable bottled water not only replaces unimproved water
      sources, but also better-quality sources, like piped and branded bottled water,
      its increasing use poses a major health risk. We investigate the motives behind
      the decision to switch to refillable bottled water in Indonesia. Findings
      indicate that this switch is driven by lifestyle motives, as well as by cost and
      availability considerations. It is mostly the young affluent households who
      switch from piped and 'other' sources to refillable bottled water. In rural
      areas, the tendency to make this switch is negatively affected by availability
      problems and the higher price of refillable bottled water. Availability and cost
      also influence the switch from branded bottled to refillable bottled water, but
      here it is the poorer households who have a higher propensity to switch. Further
      exploration of the lifestyle motive and affordability issues, as well as better
      monitoring of the refilling depots, are needed to improve the quality of drinking
      water in Indonesia and other emerging countries.

PMID- 29215363
TI  - Nano-TiO2, ultrasound and sequential nano-TiO2/ultrasonic degradation of N-acetyl
      para-aminophenol from aqueous solution.
AB  - The application of nano-TiO2 as adsorbent combined with ultrasound for the
      degradation of N-acetyl-para-aminophenol (AAP) from aqueous solution was
      investigated. The nano-TiO2 was characterized by means of powder X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), energy dispersive spectroscopy (EDS), and attenuated total
      reflection-Fourier transform infrared spectroscopy (ATR-FTIR). Experimental
      results revealed that the adsorption of AAP by nano-TiO2 fitted the pseudo-second
      order kinetic model, the equilibrium could be explained by the Freundlich
      isotherm and the treatment process is exothermic. The optimum removal efficiency
      of AAP (128.89 mg/g (77.33%)) was achieved at pH 4 when 0.03 g of nano-TiO2 was
      mixed with 50 mL of 100 mg/L AAP aqueous solution at ambient temperature, 60 min
      contact time, and a stirring speed of 120 rpm. Ultrasound at 20 kHz and pH 3 was
      favorable and it resulted in 52.61% and 57.43% removal efficiency with and
      without the addition of nano-TiO2, respectively. The degradation of AAP by
      ultrasound followed by nano-TiO2 treatment resulted in approximately 99.50%
      removal efficiency. This study showed that a sequential ultrasound and nano-TiO2
      treatment process could be employed for the removal of AAP or other emerging
      water and wastewater contaminants.

PMID- 29215364
TI  - Corrigendum: Journal of Water and Health 15 (2), 262-272: Impact of surface
      maintenance on BioSand filter performance and flow, Sarah Singer et al., doi:
      10.2166/wh.2017.129.

PMID- 29215365
TI  - Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory
      Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing
      Protective One-lung Ventilation.
AB  - BACKGROUND: Arterial oxygenation is often impaired during one-lung ventilation,
      due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5
      ml/kg predicted body weight) in the context of a lung-protective approach
      exacerbates atelectasis. This study sought to determine the combined physiologic
      effects of positive end-expiratory pressure and low VT during one-lung
      ventilation. METHODS: Data from 41 patients studied during general anesthesia for
      thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and
      respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O
      during bilateral lung ventilation and one-lung ventilation and, subsequently,
      during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory
      pressure. Shunt fraction and high V/Q were measured using variation of inspired
      oxygen fraction and measurement of respiratory gas concentration and arterial
      blood gas. The level of positive end-expiratory pressure was applied in random
      order and maintained for 15 min before measurements. RESULTS: During one-lung
      ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm
      H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11%
      (5 to 16), respectively (P < 0.001). The PaO2/FIO2 ratio increased significantly
      only at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). Driving
      pressure decreased from 16 +/- 3 cm H2O at a positive end-expiratory pressure of
      0 cm H2O to 12 +/- 3 cm H2O at a positive end-expiratory pressure of 10 cm H2O (P
      < 0.001). The high V/Q ratio did not change. CONCLUSIONS: During low VT one-lung
      ventilation, high positive end-expiratory pressure levels improve pulmonary
      function without increasing high V/Q and reduce driving pressure.

PMID- 29215366
TI  - Implantable Cardioverter Defibrillators and Survival in Continuous-Flow Left
      Ventricular Assist Device Patients.
AB  - The association of an implantable cardioverter defibrillator (ICD) with survival
      in patients with left ventricular assist devices (LVADs) is not well understood.
      We evaluated all-cause mortality by the presence of an ICD at the time of LVAD
      implantation, or by ICD implantation after LVAD placement in 191 patients, using
      Kaplan-Meier survival analyses and Cox models with multivariate adjustment.
      During the median follow-up of 23 months, 33 of 129 patients (26%) with an ICD
      and 17 of 62 patients (27%) without an ICD died. Patients had similar all-cause
      mortality with or without an ICD before LVAD, after censoring for post-LVAD ICD
      implantation (log-rank p = 0.889). Multivariate models after adjustments revealed
      no statistically significant survival benefit from an ICD before LVAD (hazard
      ratio [HR]: 0.65, 95% CI: 0.27-1.57, p = 0.340). Thirty-one of 62 (50%) patients
      without an ICD before LVAD implantation subsequently received an ICD after LVAD,
      although these patients did not have significantly better survival when compared
      with those with no ICD in a time-dependent analysis (HR: 0.70, 95% CI: 0.25-1.95,
      p = 0.497). Among LVAD patients, neither a previously implanted ICD nor a new ICD
      implantation after LVAD yielded statistically significant survival benefit.
      Further studies are warranted to investigate the role of ICD implantation in LVAD
      patients.

PMID- 29215367
TI  - Interperforator Flow Pattern and Clinical Application of Distal Extended Peroneal
      Artery Perforator Flaps.
AB  - INTRODUCTION: Peroneal artery perforator flaps are the most widely used pedicled
      flaps for soft tissue defects of the distal lower extremity. Most research
      regarding peroneal artery flaps focuses on the location, diameter, and number of
      peroneal artery perforators. However, there is little literature regarding
      interperforator flow patterns within the peroneal artery perforator flaps. The
      aims of the present study were to describe interperforator flow patterns of the
      distally based extended peroneal artery perforator flaps through digital
      subtraction angiography and review their clinical application. METHODS: Twelve
      consecutive patients underwent digital subtraction angiography of the lower-limb
      arteries. The number and classification of peroneal artery perforators and the
      interperforator flow patterns were observed. Based on these observations,
      distally based extended peroneal artery perforator flaps were designed to repair
      nonhealing wounds located on the ankles and feet of 14 patients. RESULTS: The
      peroneal artery gives out grades I to IV perforators in the lateral leg. There
      were 2 to 7 grade I perforators and true anastomoses between adjacent grade II
      perforators, which generate directly linked vessels in the middle leg. The grade
      III or IV perforators form a reticular vascular network through a large number of
      chock and potential anastomoses. All flaps survived and had excellent appearance
      and texture. CONCLUSIONS: Distally based extended peroneal artery perforator
      flaps appear reliable for repairing wounds located on or around the ankle and
      front foot. However, whether the middle perforator or peroneal artery should be
      used depends on the condition of the anastomosis between direct linking vessels
      and the distal perforator.

PMID- 29215369
TI  - From Data to Practice: Increasing Awareness of Opioid Prescribing Data Changes
      Practice.
AB  - : We hypothesized that the recent attention to the opioid epidemic, combined with
      internal dissemination of data on prescribing practices, impacted our
      institution's opioid prescribing at discharge from elective surgery. We reviewed
      our recent practice to assess whether this increasing awareness resulted in
      reductions of opioid prescriptions for patients with acute pain. Data on
      prescribing for patients undergoing elective surgery between 2016 and early 2017
      demonstrated that opioid prescribing practices have improved in the recent era
      without an observed increase in refill rates. Although additional work is needed
      to further improve standardization and reduce opioid prescribing, these data
      suggest that increased awareness may be an important first step in improving
      opioid prescribing practices.

PMID- 29215368
TI  - Numeracy and Interpretation of Prognostic Estimates in Intracerebral Hemorrhage
      Among Surrogate Decision Makers in the Neurologic ICU.
AB  - OBJECTIVE: Clinicians caring for patients with intracerebral hemorrhage must
      often discuss prognosis and goals of care with their patients' surrogate decision
      makers, and may make numeric estimates of likelihood of survival and functional
      independence, informed by validated prediction models. Surrogates' prognostic
      estimates are often discordant with physicians', suggesting that physicians'
      numeric statements may not be accurately interpreted. We sought to assess the
      relationship between numeracy and interpretation of prognostic estimates in
      intracerebral hemorrhage among surrogate decision makers. We also assessed
      surrogates' application of prognostic estimates to decisions regarding goals of
      care. DESIGN: Single-center, survey-based, cross-sectional study. SETTING: Twenty
      two-bed neurologic ICU at an urban, academic hospital. SUBJECTS: Surrogate
      decision makers for patients admitted to the neurologic ICU. INTERVENTIONS:
      Participants completed a survey containing five clinical vignettes describing
      patients with nontraumatic intracerebral hemorrhage. For each patient, numerical
      estimates of survival and functional independence were explicitly provided, based
      on the validated outcome risk stratification scale (intracerebral hemorrhage
      score) and the Prediction of Functional Outcome in Patients with Primary
      Intracerebral Hemorrhage score. MEASUREMENTS AND MAIN RESULTS: Participants were
      asked to make their own prognostic estimates, as well as to describe their
      preferred goals of care for each hypothetical patient. Respondent demographics
      were collected, and numeracy was assessed using a modified Lipkus 11-item scale.
      Poor numeracy was common (42 of 96 total subjects) in this relatively highly
      educated population. Most prognostic estimates (55%) made by surrogates were
      discordant with the provided estimates. High numeracy correlated with better
      concordance (odds ratio, 23.9 [5.57-97.64]; p < 0.001), independent of several
      factors, including level of education and religion. Numeracy also affected goals
      of-care decisions made by surrogates. CONCLUSIONS: Poor numeracy is common among
      surrogate decision makers in an intensive care setting and poses a barrier to
      communication between surrogates and clinicians regarding prognosis and goals of
      care.

PMID- 29215370
TI  - Opioid Use After Discharge in Postoperative Patients: A Systematic Review.
AB  - BACKGROUND: Over the past 2 decades, there has been an increase in opioid use and
      subsequently, opioid deaths. The amount of opioid prescribed to surgical patients
      has also increased. The aim of this systematic review was to determine
      postdischarge opioid consumption in surgical patients compared with the amount of
      opioid prescribed. Secondary outcomes included adequacy of pain control and
      disposal methods for unused opioids. OBJECTIVE: The objective of this study is to
      characterize postdischarge opioid consumption and prescription patterns in
      surgical patients. METHODS: A systematic search in MEDLINE and EMBASE identified
      11 patient survey studies reporting on postdischarge opioid use in 3525 surgical
      patients. RESULTS: The studies reported on a variety of surgical operations,
      including abdominal surgery, orthopedic procedures, tooth extraction, and
      dermatologic procedures. The majority of patients consumed 15 pills or less
      postdischarge. The proportion of used opioids ranged from 5.6% to 59.1%, with an
      outlier of 90.1% in pediatric spinal fusion patients. Measured pain scores of
      those taking opioids ranged between 2 and 5 out of 10 and the majority of
      patients were satisfied with their pain control. Seventy percent of patients kept
      the excess opioids. Where planned disposal methods were reported, between 4% and
      59% of patients planned proper disposal. CONCLUSION: This study suggests that
      surgical patients are using substantially less opioid than prescribed. There is a
      lack of awareness regarding proper disposal of leftover medication, leaving
      excess opioid that may be used inappropriately by the patient or others.
      Education for providers and clinical practice guidelines that provide guidance on
      prescription of outpatient of opioids are required.

PMID- 29215371
TI  - Pushing the Envelope in Perihiler Cholangiocellularcarcinoma Surgery: TIPE-ALPPS.

PMID- 29215372
TI  - Efficacy and safety of apatinib as second-line therapy for advanced gastric
      cancer: a single-center observational study.
AB  - Apatinib has been proven to be effective and safe among patients in the third
      line treatment of advanced gastric cancer in phase II and III trials. We aimed to
      evaluate its efficacy and safety in second-line practice, and to explore the
      factors associated with efficacy. Between April 2015 and May 2017, a total of 23
      patients with advanced gastric adenocarcinoma or adenocarcinoma of
      gastroesophageal junction were enrolled and followed up retrospectively after
      failing the first line of systemic therapy. The median progression-free survival
      was 4.43 months (95% confidence interval: 1.63-7.22) and the median overall
      survival was 9.11 months (95% confidence interval: 8.22-9.99). Two patients
      achieved a partial response and 14 patients achieved stable disease. The disease
      control rate was 69.6% and the objective response rate was 8.7%. The most common
      adverse events over grade 3 were hypertension (8.7%) and thrombocytopenia (8.7%).
      No treatment-related death was documented during the drug administration.
      Apatinib is an effective regimen for the second-line treatment of advanced
      gastric and gastroesophageal cancer with manageable toxicity.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- 29215373
TI  - Mangiferin prevents the growth of gastric carcinoma by blocking the PI3K-Akt
      signalling pathway.
AB  - The aim of the present study was to investigate the effects of mangiferin on
      gastric carcinoma cells and to determine the possible mechanisms underlying such
      effects. The MTT assay was performed to evaluate the antiproliferative effect of
      mangiferin. Following treatment, apoptosis rates of SGC-7901 were established by
      flow cytometry and laser confocal microscopy, and western blot analysis was used
      to detect the expression of apoptosis-related proteins. The MTT assay showed that
      mangiferin inhibited the proliferation of SGC-7901 and BCG-823 cells in a dose
      dependent and time-dependent manner. After SGC-7901 cells were exposed to
      mangiferin for 24, 48 and 72 h, the half-maximal inhibitory concentration values
      were 16.00, 8.63 and 4.79 umol/l, respectively. SGC-7901 cell apoptosis induced
      by mangiferin was observed by Annexin V/PI doubling staining and terminal
      deoxynucleotidyl transferase dUTP nick end labeling-positive staining. We found a
      significant decrease in Bcl-2, Bcl-xL and Mcl-1 expression and a significant
      increase in Bax, Bad and cleaved caspase-3 and caspase-9 expression in SGC-7901
      cells by mangiferin treatment. Moreover, mangiferin significantly decreased the
      levels of p-PI3K, p-Akt and p-mTOR, but had no effects on those of PI3K, Akt and
      mTOR in epidermal growth factor-treated SGC-7901 cells. Interestingly, the
      proapoptotic effect of mangiferin on SGC-7901 cells was partially blocked by the
      Akt activator SC79, whereas LY294002 significantly increased mangiferin-induced
      apoptosis and growth inhibition. Taken together, our findings indicate that
      mangiferin effectively inhibits cell growth and induces apoptosis of gastric
      cancer cells through inhibiting the PI3K/Akt pathways with relative safety, and
      may be used as a novel chemotherapeutic agent against gastric cancer.

PMID- 29215374
TI  - Empirically derived dietary patterns and ovarian cancer risk: a meta-analysis.
AB  - Dietary patterns, which reflect overall diet and possible nutrient and food
      interactions, have been reported to be related to ovarian cancer (OC) risk.
      However, studies on the relationship between dietary patterns and OC risk have
      been inconsistent. Thus, we carried out a systematic meta-analysis to assess the
      relationship between dietary patterns and the risk of OC. Relevant studies are
      identified by searching the Medline and Embase electronic databases up to
      December 2016. The Cochrane Q statistic and the I statistical were used to
      evaluate heterogeneity. A total of 22 studies fulfilled the inclusion criteria
      and were included in this meta-analysis. There was evidence of a decreased risk
      for OC in the highest versus the lowest categories of healthy dietary pattern
      [odds ratio (OR)=0.86; 95% confidence interval (CI): 0.74-0.99; P=0.04]. An
      increased risk of OC was shown for the highest versus the lowest category of a
      western-style dietary pattern (OR=1.19; 95% CI: 1.01-1.41; P=0.04). No
      significant association with OC risk was observed in the highest versus the
      lowest category of a heavy drinking pattern (OR=0.89; 95% CI: 0.67-1.19; P=0.42).
      The results of this meta-analysis suggest that a healthy dietary pattern is
      associated with reduced risk for OC and a western-style dietary pattern is
      associated with an increased risk of OC. Further studies are needed to confirm
      our results.

PMID- 29215375
TI  - Pushing Critical Thinking Skills With Multiple-Choice Questions: Does Bloom's
      Taxonomy Work?
AB  - Medical school assessments should foster the development of higher-order thinking
      skills to support clinical reasoning and a solid foundation of knowledge.
      Multiple-choice questions (MCQs) are commonly used to assess student learning,
      and well-written MCQs can support learner engagement in higher levels of
      cognitive reasoning such as application or synthesis of knowledge. Bloom's
      taxonomy has been used to identify MCQs that assess students' critical thinking
      skills, with evidence suggesting that higher-order MCQs support a deeper
      conceptual understanding of scientific process skills. Similarly, clinical
      practice also requires learners to develop higher-order thinking skills that
      include all of Bloom's levels. Faculty question writers and examinees may
      approach the same material differently based on varying levels of knowledge and
      expertise, and these differences can influence the cognitive levels being
      measured by MCQs. Consequently, faculty question writers may perceive that
      certain MCQs require higher-order thinking skills to process the question,
      whereas examinees may only need to employ lower-order thinking skills to render a
      correct response. Likewise, seemingly lower-order questions may actually require
      higher-order thinking skills to respond correctly. In this Perspective, the
      authors describe some of the cognitive processes examinees use to respond to
      MCQs. The authors propose that various factors affect both the question writer
      and examinee's interaction with test material and subsequent cognitive processes
      necessary to answer a question.

PMID- 29215376
TI  - Why Open-Ended Survey Questions Are Unlikely to Support Rigorous Qualitative
      Insights.
AB  - Health professions education researchers are increasingly relying on a
      combination of quantitative and qualitative research methods to explore complex
      questions in the field. This important and necessary development, however,
      creates new methodological challenges that can affect both the rigor of the
      research process and the quality of the findings. One example is "qualitatively"
      analyzing free-text responses to survey or assessment instrument questions. In
      this Invited Commentary, the authors explain why analysis of such responses
      rarely meets the bar for rigorous qualitative research. While the authors do not
      discount the potential for free-text responses to enhance quantitative findings
      or to inspire new research questions, they caution that these responses rarely
      produce data rich enough to generate robust, stand-alone insights. The authors
      consider exemplars from health professions education research and propose
      strategies for treating free-text responses appropriately.

PMID- 29215377
TI  - Six Strategies for Effective Learning.

PMID- 29215378
TI  - Developing Resident-Sensitive Quality Measures: A Model From Pediatric Emergency
      Medicine.
AB  - PURPOSE: To begin closing the gap with respect to quality measures available for
      use among residents, the authors sought to identify and develop resident
      sensitive quality measures (RSQMs) for use in the pediatric emergency department
      (PED) setting. METHOD: In May 2016, the authors reviewed National Quality
      Measures Clearinghouse (NQMC) measures to identify resident-sensitive measures.
      To create additional measures focused on common, acute illnesses (acute asthma
      exacerbation, bronchiolitis, closed head injury [CHI]) in the PED, the authors
      used a nominal group technique (NGT) and Delphi process from September to
      December 2016. To achieve a local focus for developing these measures, all NGT
      and Delphi participants were from Cincinnati Children's Hospital Medical Center.
      Delphi participants rated measures developed through the NGT in two areas:
      importance of measure to quality care and likelihood that measure represents the
      work of a resident. RESULTS: The review of NQMC measures identified 28 of 183 as
      being potentially resident sensitive. The NGT produced 67 measures for asthma, 46
      for bronchiolitis, and 48 for CHI. These were used in the first round of the
      Delphi process. After two rounds, 18 measures for asthma, 21 for bronchiolitis,
      and 21 for CHI met automatic inclusion criteria. In round three, participants
      categorized the potential final measures by their top 10 and next 5. CONCLUSIONS:
      This study describes a template for identifying and developing RSQMs that may
      promote high-quality care delivery during and following training. Next steps
      should include implementing and seeking validity evidence for the locally
      developed measures.

PMID- 29215379
TI  - Improving Patient-reported Pain During Radiotherapy Through Nurse Involvement and
      Patient Education.
AB  - OBJECTIVES: Pain management during radiotherapy helps assess quality of care. By
      establishing an intervention to address pain during on-treatment visits (OTVs),
      we aim to lower patient-reported pain scores. METHODS: A total of 171 patients
      were included in the analysis: 58 were retrospectively reviewed to provide a
      control and 113 were prospectively enrolled and evaluated after the intervention.
      The intervention included (1) a pain management in-service performed with the
      resident physician and nurses, (2) distribution of pain management educational
      materials, and (3) nurse consultation for patients with a pain score >=5 within 2
      days of the in-service. Study aims were to reduce the number of pain scores >=5
      by 30% and increase the number of pain scores documented during every OTV to
      >90%. RESULTS: Median patient age was 65 years. Before the intervention, the
      average DVPRS score at initial consultation was 2 (range, 0 to 9) and 98% of
      patients had scores documented during OTVs. Overall, 26% (44/171) of OTV scores
      measured >=5. Following the intervention, average DVPRS score at initial
      consultation was 2 (range, 0 to 10) and 99% of scores were documented during
      OTVs. About 14% (49/341) of patient-reported scores were >=5, representing an
      ~50% relative reduction (P=0.023). The number of patients with 2+ pain scores >=5
      was reduced from 21% (12/58) before the intervention to 11% (12/109) after the
      intervention (P=0.1068). CONCLUSION: Involving nursing staff in the education and
      follow-up of patients with uncontrolled pain during radiotherapy led to an ~50%
      relative reduction in patient-reported DVPRS scores of 5+ during weekly OTVs.

PMID- 29215380
TI  - Applying the Ottawa subarachnoid haemorrhage rule on a cohort of emergency
      department patients with headache.
AB  - OBJECTIVE: The Ottawa subarachnoid haemorrhage (SAH) rule suggests that alert
      patients older than 15 years with a severe nontraumatic headache reaching maximum
      intensity within 1 h and absence of high-risk variables effectively have a SAH
      ruled out. We aimed to determine the proportion of emergency department (ED)
      patients with any headache fulfilling the entry criteria for the Ottawa SAH rule.
      PATIENTS AND METHODS: The Ottawa SAH rule was applied retrospectively in a
      substudy of a prospective snapshot of 34 EDs in Queensland, Australia, carried
      out over 4 weeks in September 2014. Patient aged 18 years and older with a
      nontraumatic headache of any potential cause were included. Clinical data and
      results of investigations were collected. RESULTS: Data were available for 644
      (76%) patients. A total of 149 (23.1%, 95% confidence interval: 20.0-26.5%)
      fulfilled and 495 (76.9%, 95% confidence interval: 73.5-80.0%) did not fulfil the
      entry criteria. In patients who fulfilled the entry criteria, 30 (<5% overall)
      did not have any high-risk variables for SAH. In patients who fulfilled the entry
      criteria and had at least 1 high-risk feature, almost half (46%) received a
      computed tomographic brain. No SAH were missed. CONCLUSION: In this descriptive
      observational study, the majority of ED patients presenting with a headache did
      not fulfil the entry criteria for the Ottawa SAH rule. Less than 5% of the
      patients in this cohort could have SAH excluded on the basis of the rule. More
      definitive studies are needed to determine an accepted benchmark for the
      proportion of patients receiving further work-up (computed tomographic brain)
      after fulfilling the entry criteria for the Ottawa SAH rule.

PMID- 29215381
TI  - Has the Licensing Act 2003 affected violence rates in England and Wales? A
      systematic review of hospital and police studies.
AB  - Violence has been declining in the UK for two decades, with most assaults being
      alcohol related. The Licensing Act 2003 (England and Wales) aimed to reduce
      alcohol-related crime, giving local authorities control over premises licensing.
      We performed a systematic review of original research with the primary outcome of
      change in violence rates since the Act's implementation, including hospital
      defined and police-defined measures of violence. Our secondary outcome was
      temporal distribution of violence. Fifteen studies were included, which were of
      overall poor quality. Seven found reduced violence rates after the Act's
      implementation, three found increased rates and five found no significant change.
      A subset of nine studies analysed temporal distribution, eight finding
      displacement of incidents later. This is the most complete analysis to date of
      the effect of this Act on violence, finding a lack of reliable evidence to answer
      the research question, but little to suggest that the Act has markedly impacted
      already-declining violence rates.

PMID- 29215382
TI  - Initial Treatment in Septic Arthritis: Medical Versus Surgical Approach: An 8
      Year, Single Center in Spain Experience.
AB  - OBJECTIVE: The aim of this study was to compare the functional results of 2
      different procedure types, medical or surgical, which are used in treating native
      joint septic arthritis. METHODS: In this retrospective cohort study, we reviewed
      clinical registries of patients admitted to a single third-level hospital with
      the diagnosis of septic arthritis during the period of January 1, 2008, to
      January 31, 2016. RESULTS: A total of 63 cases of septic arthritis were
      identified in which the initial approach for 49 patients was medical
      (arthrocentesis), whereas the initial approach for 14 patients was surgical
      (arthroscopy or arthrotomy). Of the 49 patients who received initial medical
      treatment (IMT), 15 patients (30%) later required surgical treatment because of
      poor progress. The median age of the patients was 60 (SD, 18) years. The group
      who received IMT had a greater median age than did those who received initial
      surgical treatment (median, 64 years [interquartile range {IQR}, 54-76 years],
      vs. 48 years [IQR, 30-60 years]). There was a greater percentage of male patients
      in the surgical group (78% vs. 42% [P = 0.018]). Thirty percent of the medical
      group had been receiving corticosteroid treatment (P = 0.018). Results of
      complete recovery of joint functionality showed no significant differences after
      1 year (68% with MT vs. 67% with ST, P = 0.91). Both groups had similar symptom
      duration until diagnosis, duration of antibiotic therapy (median, 30 days [IQR,
      28-49 days], vs. 29.5 days [IQR, 27-49] days), and mortality rate (3 in the
      medical group). CONCLUSIONS: The results of the study show that initial surgical
      treatment in patients with native joint septic arthritis is not superior to IMT.
      However, half of the patients with shoulder and hip infections treated with IMT
      eventually required surgical intervention, suggesting that perhaps this should be
      the preferred initial approach in these cases.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- 29215383
TI  - Mood-Stabilizing Anticonvulsants, Spina Bifida, and Folate Supplementation:
      Commentary.
AB  - PURPOSE/BACKGROUND: High risks of neural tube defects and other teratogenic
      effects are associated with exposure in early pregnancy to some anticonvulsants,
      including in women with bipolar disorder. METHODS/PROCEDURES: Based on a
      semistructured review of recent literature, we summarized findings pertaining to
      this topic. FINDINGS/RESULTS: Valproate and carbamazepine are commonly used
      empirically (off-label) for putative long-term mood-stabilizing effects. Both
      anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of
      neural tube defects (especially spina bifida) and other major malformations are
      especially great with valproate and can arise even before pregnancy is diagnosed.
      Standard supplementation of folic acid during pregnancy can reduce risk of
      spontaneous spina bifida, but not that associated with valproate or
      carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use
      in bipolar disorder and appears not to have teratogenic effects in humans.
      IMPLICATIONS/CONCLUSIONS: Lack of protective effects against anticonvulsant
      associated neural tube defects by folic acid supplements in anticipation of and
      during pregnancy is not widely recognized. This limitation and high risks of
      neural tube and other major teratogenic effects, especially of valproate,
      indicate the need for great caution in the use of valproate and carbamazepine to
      treat bipolar disorder in women of child-bearing age.

PMID- 29215384
TI  - Update on Psychotropic Drug Prescribing in the United States: 2014-2015.

PMID- 29215385
TI  - Restless Legs Syndrome and Schizophrenia: A Case Report.

PMID- 29215386
TI  - Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1:
      Regulatory Context and Risk Management.
AB  - PURPOSE: This article brings to the attention of drug developers the Food and
      Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of
      Abuse Potential and provides practical suggestions about compliance with the
      Guidance. PROCEDURES: The Guidance areas are reviewed, analyzed, and placed in
      the context of current scientific knowledge and best practices to mitigate
      regulatory risk. FINDINGS: The Guidance provides substantial new detail on what
      needs to be done at all stages of drug development for central nervous system
      active drugs. However, because many psychopharmacologic agents have unique
      preclinical and clinical features, the plan for each agent needs to be not only
      carefully prepared but also reviewed and approved by the FDA. Examples are
      provided where assumptions about interpretation of the Guidance can delay
      development. CONCLUSIONS: If the expertise and experience needed for assessing
      abuse potential during drug development do not exist within a company, external
      preclinical and clinical expert should be involved. Consultation with the FDA is
      encouraged and important because the specific requirements for each drug will
      vary.

PMID- 29215387
TI  - Historical Trends in the Diagnosis of Peduncular Hallucinosis.
AB  - BACKGROUND: Peduncular hallucinosis (PH) describes the clinical syndrome of
      vivid, dream-like visual hallucinations that intrude on normal wakefulness.
      Additional clinical deficits, especially ophthalmoparesis, have historically been
      an important part of the diagnosis and localization of this syndrome. We examined
      how modern neuroimaging has impacted the diagnosis of PH. METHODS: We reviewed
      all available cases of PH, including 3 of ours and all previously reported in the
      literature. We determined whether other eye movement abnormalities were part of
      the clinical presentation and whether a neuroimaging study was performed to make
      the diagnosis. RESULTS: A total of 85 cases were identified and evaluated. Eye
      movement abnormalities were present in 12/15 (80%) without a neuroimaging study
      but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P =
      0.001). CONCLUSIONS: Although eye movement abnormalities historically have been
      considered a key localizing clinical feature supporting the diagnosis of PH, we
      found that in the era of modern neuroimaging, co-occurring eye movement
      abnormalities are far less frequent and are not a requisite feature of the
      diagnosis.

PMID- 29215388
TI  - Case of Bilateral Sequential Nonarteritic Ischemic Optic Neuropathy After
      Rechallenge With Sildenafil.

PMID- 29215389
TI  - Horizontal Gaze Palsy With Progressive Scoliosis: Two Novel ROBO3 Mutations in a
      Compound Heterozygous Sporadic Case.

PMID- 29215390
TI  - Does Podcast Use Enhance Critical Thinking in Nursing Education?
AB  - The purpose of this pilot interventional study was to examine relationships
      between adjunctive podcast viewing and nursing students' critical thinking (CT)
      abilities. Participants were last semester/preceptorship nursing students. The
      intervention group was given unrestricted access to a CT podcast. There was no
      statistical significance between Health Sciences Reasoning Test pretest and
      posttest scores, the number of times the podcast was viewed, and specific
      demographic factors. The results suggest that CT podcast viewing did not improve
      CT abilities. However, Likert scale results indicated students liked this method
      of learning. Demographic factors and sample size were limited, and further
      research is recommended.

PMID- 29215391
TI  - Engaging Nursing Students: Integrating Evidence-Based Inquiry, Informatics, and
      Clinical Practice.
AB  - The nursing research class requires faculty to create a spirit of inquiry while
      integrating technology, flexibility, and responsiveness to student needs. This
      article discusses new pedagogies to actively engage students in the evidence
      based nursing process and the achievement of course learning outcomes. Through
      course exemplar, the author demonstrates a creative method to engage traditional
      baccalaureate nursing students in a nursing project that links evidence to
      improved patient outcomes.

PMID- 29215392
TI  - Physiologic uptake of 18F-FDG in transposed ovaries may mimic metastasis on 18F
      FDG PET/CT imaging.
AB  - BACKGROUND: Ovarian transposition is aimed at preserving ovarian function before
      irradiation in pelvic malignancies. The extrapelvic location of the ovaries and
      their physiologic fluorine-18-fluorodeoxyglucose (F-FDG)-uptake is a potential
      source of misdiagnosis as metastasis on F-FDG PET/CT. We describe the F-FDG
      PET/CT characteristics of transposed ovaries and their changes over time.
      PATIENTS AND METHODS: We reviewed F-FDG PET/CT studies of all consecutive women
      with pelvic malignancies who underwent ovarian transposition between 2007 and
      2013. Studies were grouped according to the time period over which they were
      carried out. Findings were categorized by location, size, appearance
      (solid/mixed/cystic), presence of surgical clips, ovarian F-FDG uptake (maximum
      standardized uptake value), and attenuation values on CT (Hounsfield units).
      Group time-period differences were assessed. RESULTS: Seventy-nine F-FDG PET/CT
      studies were reviewed, 30 before and 49 after transposition. Time-period groups
      after transposition were up to 4 months (18 studies), 4.1-12 months (n=14), and
      more than 12 months (n=17). After transposition, ovaries were located mainly in
      the paracolic gutter (n=32) and subhepatic regions (n=18). Surgical clips were
      present in 67%. Both ovaries appeared more solid 1 year after surgery than
      preoperatively (13.7% before vs. 61.3% after surgery; P<0.001). Transient F-FDG
      avidity was observed in 11 ovaries. Hounsfield unit values were higher within 4
      months after surgery than preoperatively, reverting thereafter to preoperative
      values. CONCLUSION: After ovarian transposition, nonanatomic location, loss of
      cysts formation in favor of solid appearance over time, and intermittent F-FDG
      uptake of functioning transposed ovaries might mimic metastatic lesions. Careful
      interpretation of F-FDG PET/CT findings is mandatory in women with pelvic
      malignancies who have undergone ovarian transposition.

PMID- 29215393
TI  - Therapeutic Effects of Lamellar Keratoplasty on Terrien Marginal Degeneration.
AB  - PURPOSE: To evaluate the therapeutic effects of lamellar keratoplasty (LK) on
      Terrien marginal degeneration (TMD). METHODS: Retrospective interventional case
      series. Medical records of 63 patients (71 eyes) who received LK for TMD at
      Qingdao Eye Hospital, Shandong Eye Institute from December 1995 to March 2014
      were reviewed. A total of 56 eyes were treated with partial LK and 15 eyes with
      total LK. Complications, visual acuity recovery, and graft status were evaluated.
      RESULTS: Mean age of the patients was 50.4 +/- 16.8 years. The follow-up period
      was 2.5 +/- 0.9 years. The uncorrected distance visual acuity (UDVA) increased
      from preoperative 0.90 +/- 0.44 logarithm of the minimum angle of resolution
      (logMAR) to 0.53 +/- 0.27 logMAR at 1 year after surgery (t = 16.256, P < 0.001).
      The corrected distance visual acuity (CDVA) was 0.69 +/- 0.30 logMAR
      preoperatively, and increased to postoperative 0.38 +/- 0.22 logMAR (t = -19.982,
      P < 0.001). After surgery, mean astigmatism was 5.33 +/- 2.44 diopters (D)
      compared with preoperative 10.19 +/- 4.32 D (t = 7.351, P < 0.001), and the
      spherical equivalent decreased from preoperative -2.23 +/- 2.34 D to -0.75 +/-
      2.04 D (t = -2.677, P = 0.012). There was a significant difference in UDVA,
      DeltaUDVA, CDVA, DeltaCDVA, and refractive astigmatism between the partial LK and
      total LK groups. The most common intraoperative complication was corneal
      perforation. The postoperative complications included double anterior chamber,
      persistent graft epithelium defects, corneal vascularization, immune rejection,
      graft ulcers, cataract, and recurrence of marginal degeneration. CONCLUSIONS: LK
      can effectively reduce refractive errors, improve visual acuity, and reduce the
      risk of corneal perforation for patients with TMD. The visual acuity after
      partial LK is superior to that after total LK.

PMID- 29215394
TI  - Visual Outcomes and Aberrometric Changes With Topography-Guided Photorefractive
      Keratectomy Treatment of Irregular Astigmatism After Penetrating Keratoplasty.
AB  - PURPOSE: To evaluate the visual acuity and keratometric and aberrometric changes
      in patients with corneal transplants (PKP), who underwent topography-guided
      photorefractive keratectomy (TG-PRK) with mitomycin C (MMC). METHODS: In this
      case study, 15 patients with spherical equivalents ranging from -11.00 to -0.25
      diopters (D) who underwent penetrating corneal transplantation and had irregular
      astigmatism ranging from -7.5 to -2.0 D underwent TG-PRK with MMC. Corneal
      topography and wavefront of all patients were measured preoperatively and 12
      months postoperatively. RESULTS: Twelve months after TG-PRK with MMC, 46% of eyes
      achieved a best spectacle-corrected visual acuity (BSCVA) of 20/20 compared with
      1 eye preoperatively (P = 0.0221, chi test). The BSCVA did not improve in 1
      patient and increased by 1 line or more in all others. Astigmatism decreased
      significantly (P = 0.003) from 5.10 +/- 0.4 D to 3.37 +/- 0.06 D, the corneal
      best-fit sphere increased and keratometry measurements flattened significantly (P
      = 0.0001 for both comparisons), and the corneal total root mean square
      aberrations and trefoil decreased significantly (P = 0.0077 and P = 0.0054,
      respectively) from 9.11 +/- 2.56 MUm to 7.58 +/- 3.15 MUm and 2.00 +/- 1.2 to
      1.38 +/- 0.27 MUm, respectively, as measured by wavefront aberrometry.
      CONCLUSIONS: Twelve months postoperatively, the BSCVA improved significantly, the
      lines of vision increased, and astigmatism, corneal best-fit sphere, mean
      keratometry, corneal thickness, corneal root mean square total, and corneal
      spherical aberrations decreased. TG-PRK with MMC is a good alternative for
      correcting post-PKP cases with irregular astigmatism with elevated higher-order
      aberrations.

PMID- 29215395
TI  - Topical Tacrolimus as Adjuvant Therapy to Corticosteroids in Acute Endothelial
      Graft Rejection After Penetrating Keratoplasty: A Randomized Controlled Trial.
AB  - PURPOSE: To evaluate the efficacy of topical tacrolimus 0.05% as adjuvant therapy
      to corticosteroids in the treatment of acute endothelial rejection of a
      penetrating keratoplasty (PKP) graft. METHODS: Patients with the clinical
      diagnosis of acute endothelial rejection of a PKP graft were randomized into 2
      groups-group 1: receiving topical tacrolimus 0.05% as adjuvant therapy to
      corticosteroid treatment and group 2: receiving only corticosteroid treatment.
      Main outcome measures were rejection reversal, time to rejection reversal, and
      recurrence of rejection. RESULTS: Thirty-one eyes of 31 patients (17 and 14 eyes
      in group 1 and 2, respectively) were included in the study. The rejection episode
      completely resolved in 88.2% of patients in group 1 and 85.7% of patients in
      group 2 [hazard ratio = 0.60, 95% confidence interval (CI) = 0.28-1.29, P =
      0.191]. After adjusting for preoperative factors using the inverse-probability
      weighting method, the time to resolution of rejection was significantly shorter
      in group 1 than group 2 (average treatment effect = 16, 95% CI, 3.7-28.7, P =
      0.013). The recurrence rate of rejection was significantly higher in group 2
      (39.7, 95% CI, 12.8-92.6 per 1000 months of follow-up) than in group 1 (3.6, 95%
      CI, 0.05-19.9 likewise); risk ratio: 11.1, 95% CI, 1.3-95.0, P = 0.028.
      CONCLUSIONS: Topical tacrolimus 0.05% as an adjunct to steroids can hasten the
      resolution of endothelial rejection of a PKP graft and potentially decreases the
      recurrence of rejection. However, it may not improve rejection reversal success.

PMID- 29215397
TI  - Keratoconus and Personality-A Review.
AB  - PURPOSE: To assess the existing literature on the subject of keratoconus and
      personality and to propose a theory that might account for the perceived
      personality changes associated with this condition. METHODS: A literature search
      was conducted in the PubMed database using the term "keratoconus" in combination
      with keywords such as personality, psychiatry, psychology, anxiety, depression,
      or psychosis. A total of 15 articles pertaining to personality and psychiatric
      disorders in keratoconus were retained and reviewed. RESULTS: Although patients
      with keratoconus tend to score differently on personality scales compared with
      normal controls, the literature fails to substantiate the existence of a unique
      "keratoconic personality." Instead, patients with keratoconus prove to have more
      dysfunctional coping mechanisms that specifically alter their interaction with
      health care providers and may account for the persistent clinical impression of
      less respectful, conforming, and cooperative patients. CONCLUSIONS: We
      hypothesize that the stage of life at which keratoconus commonly presents plays a
      crucial role in personality and coping mechanism development that significantly
      affects behavioral patterns and the relationship with caregivers.

PMID- 29215396
TI  - Outcomes of Corneal Cross-Linking Correlate With Cone-Specific Lysyl Oxidase
      Expression in Patients With Keratoconus.
AB  - PURPOSE: To evaluate the correlation of visual and keratometry outcomes after
      corneal cross-linking (CXL) in patients with keratoconus with cone epithelium
      specific gene expression levels. METHODS: Corneal epithelium was obtained from 35
      eyes that underwent accelerated CXL (KXLII, 9 mW/cm for 10 min). Using corneal
      topography, epithelium over the cone and periphery was obtained separately from
      each subject. The ratio of gene expression for lysyl oxidase (LOX), matrix
      metalloproteinase 9 (MMP9), bone morphogenic protein 7, tissue inhibitor of
      metalloproteinase 1, collagen, type I, alpha 1, and collagen, type IV, alpha 1
      (COL IVA1) from the cone and peripheral cornea was correlated with the outcome of
      cross-linking surgery. Patients were assessed for visual acuity, keratometry,
      refraction, and corneal densitometry before and 6 months after surgery. Based on
      the change in corneal flattening indicated by DeltaKmax, the outcomes were
      classified as a higher response or lower response. RESULTS: Reduction in
      keratometric indices correlated with improved spherical equivalent after CXL.
      Preoperative levels of cone-specific LOX expression in cases with a higher
      response were significant (P = 0.001). COL IVA1, bone morphogenic protein 7, and
      tissue inhibitor of metalloproteinase 1 gene expressions were reduced in the
      cones of the subjects with a lower response. MMP9 levels were relatively lower in
      cases with a higher response compared with those with a lower response.
      CONCLUSIONS: Our study demonstrates that preoperative levels of molecular factors
      such as LOX, MMP9, and COL IVA1 aid in understanding CXL outcomes at the tissue
      level.

PMID- 29215398
TI  - A genetic risk score for fasting plasma glucose is independently associated with
      arterial stiffness: a Mendelian randomization study.
AB  - BACKGROUND: Arterial stiffness is known to be associated with a number of
      clinical conditions including hypertension, diabetes and dyslipidemia, and may
      predict cardiovascular events and mortality. However, causal links are hard to
      establish. Results from genome-wide association studies have identified only a
      few single nucleotide polymorphisms associated with arterial stiffness, the
      results have been inconsistent between studies and overlap with other clinical
      conditions is lacking. Our aim was to investigate a potential shared set of risk
      single nucleotide polymorphisms between relevant cardiometabolic traits and
      arterial stiffness. METHOD: The study population consisted of 2853 individuals
      (mean age 72 years, 40% men) from the population-based Malmo Diet and Cancer
      study, Sweden. Carotid-femoral pulse wave velocity, a marker of arterial
      stiffness, was measured with Sphygmocor. Mendelian randomization analyses were
      performed using the two-stage least square regression and multivariate inverse
      variance weighted methods. RESULTS: There were positive associations between
      arterial stiffness and genetic risk scores for type 2 diabetes (beta = 0.03, P =
      0.04) and fasting plasma glucose (beta = 0.03, P = 0.03), but not for systolic
      blood pressure, body mass index, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol or triglycerides. Multivariate inverse-variance
      weighted methods confirmed the significant positive association for fasting
      plasma glucose beta coefficients (P = 0.006), but not for type 2 diabetes beta
      coefficients (P = 0.88). CONCLUSION: Genetically elevated fasting plasma glucose,
      but not genetically elevated risk of type 2 diabetes, was associated with
      arterial stiffness suggesting a causal stiffening effect of glycemia on the
      arterial wall, independently of type 2 diabetes.

PMID- 29215399
TI  - Hemorrhage of liver and bone metastases as a result of rapid response to dual
      BRAF/MEK inhibition in metastatic melanoma: a case report.
AB  - Combination therapy using a BRAF and MEK inhibitor significantly improves both
      progression-free and overall survival in patients with BRAF V600-mutated stage IV
      melanoma. Dual MAPK inhibition achieves an objective response in the majority of
      patients. We present a case of a woman with BRAF V600E-mutated malignant melanoma
      and rapidly progressing liver, bone, and lymph node metastases. The patient
      commenced dabrafenib and trametinib with clinical and biochemical signs of
      response after 2 days. On day 3 she developed grade 3 liver hemorrhage, which was
      successfully embolized. Her anemia responded appropriately to transfusions and
      stabilized after interventional resolution of the hemorrhagic event. Subsequently
      she developed a pathological fracture of the right proximal humerus. MRI showed
      cystic bone metastases with stigmata of bleeding. To our knowledge, this is the
      first case report of a patient with hemorrhage of both liver and bone metastases
      of a melanoma. As the patient responded rapidly to dabrafenib and trametinib we
      hypothesize that the hemorrhage may be due to rapid tumor necrosis and bleeding
      of affected tumor supplying blood vessels. Our case demonstrates the importance
      of considering tumoral bleeding as a side effect of BRAF and MEK inhibition in
      responding melanoma patients. Mechanical intervention can be effective in
      resolving this treatment-related adverse event.

PMID- 29215400
TI  - Five-Year Survival and Causes of Death in Children After Intensive Care-A
      National Registry Study.
AB  - OBJECTIVES: The aim of the study was to compare long-term mortality and causes of
      death in children post admission to an ICU with a control population of same age.
      DESIGN: Longitudinal follow-up study. SETTING: Registry study of a national ICU
      register and hospital registries. PATIENTS: Children admitted to an ICU in the
      years 2009 and 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      mortality and causes of death following ICU discharge were analyzed
      retrospectively. The median follow-up period was 4.9 years (25-75th percentiles,
      4.4-5.5 yr). The causes of death in survivors 30 days after ICU discharge were
      compared with a cohort of 1 million children of the general population of same
      age. In total, 2,792 children were admitted to an ICU during the study period. Of
      those, 53 (1.9%) died in the ICU and 2,739 were discharged. Thirteen children
      died within 30 days of discharge, and 68 died between 30 days and the end of
      follow-up (December 31, 2014). In the control population (n = 1,020,407
      children), there were 1,037 deaths (0.10%) from 2009 to 2014. The standardized
      mortality rate for the children admitted to the ICU during the study period was
      53.4 (95% CI, 44.7-63.2). The standardized mortality rate for those children
      alive 1 year after discharge was 16.7 (12.1-22.6). One-year cumulative mortality
      was 3.3%. The most common causes of death in subjects alive 30 days post ICU were
      cancer (35.3%), neurologic (17.6%), and metabolic diseases (11.7%), whereas
      trauma was the most common cause in the control group (45.3%). CONCLUSIONS: There
      was an increased risk of death in a cohort of ICU-admitted children even 3 years
      after discharge. In those who survived 30 days after discharge, medical causes of
      death were dominant, whereas deaths due to trauma were most common in the control
      group.

PMID- 29215401
TI  - Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.
AB  - OBJECTIVES: The aim of this study was to determine the relaxation properties of
      ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under
      physiological conditions at 1.5 T and 3.0 T. MATERIALS AND METHODS: Ferumoxytol
      was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human
      plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37
      degrees C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate
      constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration,
      and relaxivities (r1, r2, r2*) were calculated. RESULTS: A linear dependence of
      R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with
      lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T:
      r1saline = 19.9 +/- 2.3 smM; r1plasma = 19.0 +/- 1.7 smM; r2saline = 60.8 +/- 3.8
      smM; r2plasma = 64.9 +/- 1.8 smM; r2*saline = 60.4 +/- 4.7 smM; r2*plasma = 64.4
      +/- 2.5 smM; 3.0 T: r1saline = 10.0 +/- 0.3 smM; r1plasma = 9.5 +/- 0.2 smM;
      r2saline = 62.3 +/- 3.7 smM; r2plasma = 65.2 +/- 1.8 smM; r2*saline = 57.0 +/-
      4.7 smM; r2*plasma = 55.7 +/- 4.4 smM). The dependence of relaxation rates on
      concentration in blood was nonlinear. Formulas from second-order polynomial
      fittings of the relaxation rates were calculated to characterize the relationship
      between R1blood and R2 blood with ferumoxytol. CONCLUSIONS: Ferumoxytol
      demonstrates strong longitudinal and transverse relaxivities. Awareness of the
      nonlinear relaxation behavior of ferumoxytol in blood is important for
      ferumoxytol-enhanced magnetic resonance imaging applications and for protocol
      optimization.

PMID- 29215402
TI  - Quality and Safety in Health Care, Part XXXIV: The PINNACLE Registry.
AB  - The PINNACLE (Practice INNovation And Clinical Excellence) program was started in
      2008 by the American College of Cardiology and its National Cardiovascular Data
      Registry. This was the first and now the largest countrywide prospective registry
      to improve care quality for cardiac outpatients. The registry focuses on
      reporting about the adherence to guidelines in treating individuals with high
      blood pressure, atrial fibrillation, coronary artery disease, and/or cardiac
      failure.

PMID- 29215403
TI  - SUV as a Possible Predictor of Disease Extent and Therapy Duration in Complex
      Tuberculosis.
AB  - OBJECTIVE: F-FDG PET/CT provides information on disease extension and activity in
      neoplastic and inflammatory conditions. So far, little is known about whether
      SUVmax of a reference lesion can allow a prognosis to be given regarding patient
      specific outcome parameters in complex cases of tuberculosis (TB). METHODS: We
      retrospectively identified 37 patients (21 men, 16 women; mean age, 50.4 years)
      who underwent F-FDG PET/CT for the evaluation of active TB before treatment
      initiation. The aims were to examine whether the reference lesion SUVmax differed
      between patients with standard (<=9 months) and long-term (>9 months) therapy and
      to define an SUVmax cutoff distinguishing those groups. In addition, we analyzed
      the prognostic value of SUVmax with regard to estimation of initial disease
      extent and lesion distribution pattern. RESULTS: Median therapy duration was 10
      months (interquartile range, 3.25 months), and median SUVmax was 8 (interquartile
      range, 8.54). SUVmax was significantly (P = 0.036) higher in patients treated
      longer than 9 months (10.1 vs 5.5). When applying a receiver operating
      characteristic curve analysis, an SUVmax cutoff value of 10 differentiated the
      standard and the long-term therapy group with a sensitivity of 50% and a
      specificity of 78.6% (P = 0.087). Higher SUVmax corresponded with a larger number
      of affected organ systems (P = 0.012 for <=/>1). Patients with extrathoracic
      involvement showed significantly higher SUVmax than did patients with limited
      intrathoracic disease (P = 0.024) and received significantly longer
      antimycobacterial therapy (P = 0.011). CONCLUSIONS: Reference lesion SUVmax from
      pretherapy F-FDG PET/CT may have prognostic properties in complicated cases of
      TB, especially regarding therapy duration and disease extent.

PMID- 29215404
TI  - Quality and Safety in Health Care, Part XXXIV: Coronary Artery Disease Secondary
      Prevention Medications.
AB  - There is an important opportunity for improvement in the care of cardiology
      outpatients by having greater compliance with published guidelines, and the
      PINNACLE (Practice Innovation and Clinical Excellence) Registry seeks to do that.
      One of the major areas studied by this registry is the use of secondary
      prevention medications for patients with coronary artery disease. Appropriate use
      of these medications decreases later myocardial infarctions and death from a
      cardiac cause.

PMID- 29215405
TI  - 123I-FP-CIT SPECT Accurately Distinguishes Parkinsonian From Cerebellar Variant
      of Multiple System Atrophy.
AB  - PURPOSE: Dopamine transporter SPECT imaging is a valuable tool to estimate the
      integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms.
      Evidence about SPECT differential pattern between parkinsonian and cerebellar
      forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at
      assessing whether MSA-P and MSA-C variants have a distinct semiquantitative I-FP
      CIT SPECT pattern. METHODS: We studied a unicentric 13-year (2003-2016)
      retrospective cohort of subjects with possible or probable MSA and scanned with
      the same acquisition and reconstruction SPECT protocol. Age-dependent
      semiquantitative reference limits for striatal volumes of interest, asymmetry
      indices, and caudate/putamen ratio were previously established with a percentile
      approach on a cohort of subjects with nondegenerative conditions and normal
      visual scan. RESULTS: Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA
      C) were identified (mean age, 68.2 +/- 10.1 years; male/female ratio 1.00;
      disease duration, 2.5 +/- 2.2 years; Movement Disorders Society Unified
      Parkinson's Disease Rating Scale III score, 33.8 +/- 12.4). The MSA-P subjects
      exhibited lower uptake values for all volumes of interest, for example, striatal
      uptake on the more affected side (1.10 +/- 0.51) compared with MSA-C (2.30 +/-
      0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 +/-
      24.8 vs 6.3 +/- 4.5, P = 0.028) and caudate/putamen ratio (2.26 +/- 1.23 vs 1.13
      +/- 0.17, P = 0.00148). CONCLUSIONS: The MSA-P and MSA-C subjects exhibited
      significantly distinct semiquantitative SPECT pattern with severe uptake
      impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C.
      Clinical distinction of these 2 phenotypical entities is necessary in order to
      evaluate SPECT potential to discriminate between degenerative parkinsonisms.

PMID- 29215406
TI  - Focal 18F-DOPA Uptake in Brain Parenchyma Surrounding Developmental Venous
      Anomalies.
AB  - We report the finding of increased F-DOPA uptake within parenchyma surrounding a
      developmental venous anomaly, found incidentally in a 64-year-old woman
      undergoing PET scan to assess for Parkinson's disease. Not identified on previous
      T1/T2 MRI, susceptibility-weighted imaging MRI performed post-PET scan
      demonstrated the presence of developmental venous anomaly within the left
      cerebellar hemisphere. Focal uptake of F-DOPA may suggest the presence of a brain
      tumor and prompt invasive diagnostic investigations. Nuclear medicine physicians
      should be aware of this finding when interpreting F-DOPA PET and consider
      appropriate imaging to identify venous anomalies prior to more invasive
      investigations for possible brain tumors.

PMID- 29215407
TI  - Dilated Internal Thoracic Vertebral Venous Plexus Simulating Bone Metastases on
      FDG PET/CT.
AB  - A 42-year-old woman with a newly diagnosed malignant thymoma underwent FDG
      PET/CT, which demonstrated an increased uptake in anterior mediastinal tumor and
      several pleural masses in the right hemithorax, compatible with "drop
      metastases." In addition, contrast-enhanced CT images showed hyperdense
      abnormality in T2 vertebral body, congruent with intensely increased FDG uptake,
      raising suspicion of skeletal metastasis. This is a rare but important potential
      pitfall either in CT and FDG PET/CT-a "false-positive" bony lesion not attributed
      to skeletal metastasis but to dilated internal thoracic vertebral venous plexus
      associated with collateral circulation due to superior vena cava syndrome.

PMID- 29215408
TI  - 18F-FDG PET/CT Findings of Mesenchymal Chondrosarcoma of the Orbit.
AB  - Mesenchymal chondrosarcoma of the orbit is an extremely rare and aggressive
      tumor. We report image findings of F-fluorodeoxyglucose (FDG) positron
      emission/computed tomography (PET/CT) in 2 cases, one primary case and one
      recurrent case. The F-FDG PET/CT images revealed high uptake with an SUVmax of
      6.7 and 11.7, respectively. In both cases, the HEY1-CoA2 gene fusion was
      positive. The high uptake of F-FDG in mesenchymal chondrosarcoma of the orbit
      well suggests the malignancy of this tumor.

PMID- 29215409
TI  - Imaging of Acquired Demyelinating Syndrome With 18F-FDG PET/CT.
AB  - Acquired demyelinating syndromes include acute disseminated encephalomyelitis,
      transverse myelitis and may progress to multiple sclerosis (MS). Acute
      disseminated encephalomyelitis is characterized by impairment of level of
      consciousness and multifocal neurological deficits and transverse myelitis by
      back pain, weakness and sphincter dysfunction. Only a few cases of acquired
      demyelinating syndrome have been imaged with F-FDG PET/CT. We present two such
      cases.

PMID- 29215410
TI  - Isolated Multinodular Soft-Tissue Rosai-Dorfman Disease on FDG PET/CT.
AB  - Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a
      rare systemic histiocytic disorder of unknown etiology characterized by the
      accumulation of enlarged non-Langerhans histiocytes within lymph nodes and
      extranodal sites. The histiocytes display characteristic emperipolesis
      (nondestructive engulfment of inflammatory cells) and are CD68 and S100 positive
      and CD1a negative. Although extranodal disease frequently occurs with nodal
      involvement, isolated extranodal disease is uncommon. We report a case of
      isolated localized subcutaneous multinodular disease on FDG PET/CT. We also
      include a companion classic Rosai-Dorfman case with extensive nodal involvement
      and a characteristic benign clinical course with spontaneous improvement.

PMID- 29215411
TI  - A Novel Technique to Measure the Intensity of Abnormality on GI Bleeding Scans:
      Development, Initial Implementation, and Correlation With Conventional
      Angiography.
AB  - PURPOSE: Develop a technique to quantify intensity of lower gastrointestinal
      bleeding (LGIB) on Tc-labeled red blood cell (RBC) scintigraphy, correlate with
      angiography, and determine the tool's predictive value. MATERIALS AND METHODS: An
      IRB-approved, single institution database query of GI bleeding scans performed
      between January 2013 and December 2015. Reports from all studies and imaging from
      all positive studies were reviewed. A technique was developed for scan analysis,
      allowing for calculation of percent increase of activity in the region of
      interest (ROI, area of bleeding) and ROI in the aorta and liver (controls).
      Database query determined which patients underwent angiography, and which had
      positive angiograms. Median ROI percent increase in patients with positive
      scintigraphy and positive angiography was compared to those with positive
      scintigraphy and negative angiography. RESULTS: Of 194 bleeding scans performed
      during the study period, 71 were positive for active LGIB, 37 had angiography,
      and 9 had active contrast extravasation. The new tool was used to analyze the 37
      cases with positive nuclear scans sent for angiography. Median percent increase
      in ROI activity was 50% in those with positive scan and positive angiogram and
      26.8% in those with positive scan but negative angiogram. Using ROI percent
      change quartiles, we observed a statistically significant association between
      percent increase in ROI activity from baseline and the probability of having a
      positive angiogram (Cochran-Armitage trend test, P = 0.01), such that there are
      no positive angiogram cases when ROI change was <20% and a majority of the
      positive angiogram cases (67%) in the highest quartile. CONCLUSIONS: Utilization
      of processing protocol to determine percent increase in activity from baseline
      within ROI of active LGIB on scintigraphy has predictive value in determining
      which patients will not benefit from conventional angiography.

PMID- 29215412
TI  - Serial FDG-PET/CT Imaging in the Management of Cardiac Sarcoidosis.
AB  - A 60-year-old woman with biopsy-proven cardiac sarcoidosis status post
      implantable cardioverter defibrillator placement presented with periodic
      dizziness and dyspnea on exertion. Myocardial perfusion scan demonstrated a
      moderate sized, fixed perfusion defect along the mid to proximal anteroseptal
      wall of the left ventricle, with better perfusion on stress images. FDG-PET/CT
      demonstrated corresponding focal FDG avidity of the mid to proximal anteroseptal
      wall, suggestive of active cardiac sarcoidosis. Because of severe side effects,
      mycophenolate mofetil was discontinued, and the patient received low-dose steroid
      therapy. At 7-month follow-up FDG PET/CT, there was increased FDG avidity in the
      same regions, indicating worsening cardiac sarcoidosis.

PMID- 29215413
TI  - FDG-PET/CT Guided Biopsy in Angiosarcoma of Bone: Diagnosis, Staging and Beyond.
AB  - Primary angiosarcoma of the bone (PAB) is a particularly rare and aggressive form
      of malignancy in the spectrum of vascular tumours, and it accounts for less than
      1% of sarcomas. This case of PAB, diagnosed thanks to FDG-PET/CT guided biopsy,
      is a paradigm of how powerful are clinical informations that can be derived by a
      F-FDG PET/CT, in view of negative or inconclusive imaging of conventional
      radiology, starting from the metabolic characterization of an equivocal finding,
      the possibility to drive the biopsy towards the most active site, the accurate
      total body staging, the stratification of prognosis and early therapy assessment.

PMID- 29215414
TI  - Unexpected Detection of Urethral Stone on 18F-NaF PET/CT.
AB  - A 48-year-old man was referred for an F-NaF PET/CT to examine his lower back
      pain. The images did not identify any osseous lesion. Unexpectedly, the images
      showed elevated activity in a urethral stone. The patient received urinary
      surgery for stone removal.

PMID- 29215415
TI  - Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis Mimicking
      Lymphoma on FDG PET/CT.
AB  - A 15-year-old boy with fever, pancytopenia, and hepatosplenomegaly was diagnosed
      as hemophagocytic lymphohistiocytosis (HLH). F-FDG PET/CT showed hypermetabolic
      foci in the liver, spleen, and bone marrow, as well as multiple FDG-avid lymph
      nodes, which were highly suggestive of lymphoma. Specimens from splenectomy
      depicted a large number of macrophages/histiocytes with hemophagocytosis of
      erythrocytes, without evidence of malignancy. Considering increased Epstein-Barr
      virus (EBV) DNA in peripheral blood and positive staining for EBV-encoded RNA in
      the spleen, EBV-associated HLH was confirmed. This case indicates that FDG-avid
      foci in the liver, spleen, and bone marrow may also be seen in EBV-associated
      HLH.

PMID- 29215416
TI  - Cardiac Fibroma: An Uncommon Cause of a Fixed Defect on Myocardial Perfusion
      Imaging.
AB  - A 66-year-old woman was referred for evaluation of coronary artery disease.
      Myocardial perfusion imaging (MPI) was performed, and showed a medium-sized,
      severe fixed perfusion defect in the inferior and inferolateral wall from apex to
      midcavity. On review of prior imaging, it was noted that the patient had an
      incidental finding of an intramural cardiac mass on chest CT performed 8 years
      prior. Subsequent cardiac MRI showed findings consistent with a cardiac fibroma
      in the left ventricle, at the location of the perfusion defect on MPI. Our case
      demonstrates an uncommon cause of a fixed perfusion defect on MPI.

PMID- 29215417
TI  - Muramyl Dipeptide Enhances Thermal Injury-Induced Autophagy and Inflammatory
      Cytokine Response of Lungs via Activation of NOD2/Rick Signaling Pathway in Rats.
AB  - OBJECTIVE: Nucleotide-binding oligomerization domain 2 (NOD2) is the innate
      receptor of muramyl dipeptide (MDP). Our previous study revealed that MDP could
      enhance thermal injury-induced inflammatory cytokine production and organ
      function injury in rats. The present study was to determine the effect of MDP on
      autophagy and NOD2/receptor-interacting serine/threonine protein kinases (RICK)
      signaling pathway of lung injury after thermal injury. METHODS: Forty male
      Sprague-Dawlay rats were randomly divided into four groups: normal control (NC)
      group, MDP group, Scald group, and MDP + Scald group. Scald group only suffered
      20% total body surface area third-degree (TBSA) thermal injury. MDP group was
      only administered 5.0 mg/kg MDP through the left femoral vein; 5.0 mg/kg MDP was
      administered through the left femoral vein at 24 h after thermal injury in the
      MDP + Scald group. RESULTS: TBSA thermal injury (20%) not only significantly
      increased the plasma inflammatory cytokines production, but also elevated the
      expression of LC3-I/II, the accumulation of autophagosome in the lung tissue.
      Compared with the Scald group, MDP + Scald double hit led to more serious
      inflammatory responses and higher expression of NOD2 mRNA, RICK, NF-kappaB p65,
      LC3-I/II, and the accumulation of more autophagosome in the lung tissue.
      CONCLUSIONS: MDP enhances thermal injury-induced autophagy and proinflammatory
      cytokine response of lung injury, which could be achieved via activating the
      NOD2/RICK signaling pathway in rats.

PMID- 29215418
TI  - Switching From Ticagrelor or Prasugrel to Clopidogrel.
AB  - Ticagrelor and prasugrel are newer antiplatelet drugs which, like clopidogrel,
      block the P2Y12 platelet receptor to inhibit platelet aggregation. Compared with
      clopidogrel, both ticagrelor and prasugrel have greater clinical efficacy but
      also have a higher risk of bleeding and are much more costly. Therefore, some
      institutions and providers switch patients from ticagrelor or prasugrel to
      clopidogrel in an effort to lower bleeding risk, stem costs, or otherwise ensure
      that patients can safely adhere to long-term P2Y12 inhibitor therapy. From a
      pharmacodynamic perspective, switching patients from ticagrelor or prasugrel to
      clopidogrel comes at a cost of less antiplatelet efficacy. However, it is unclear
      if antiplatelet efficacy is diminished enough to affect clinical outcomes. This
      is because clinical trial data investigating such a switch is scant, leaving the
      clinician unsure as to the acceptability of this practice. Current clinical trial
      data have thus far not shown any clinical detriment from switching from
      ticagrelor or prasugrel to clopidogrel, but there are many limitations to these
      investigations. So although a large-scale switch of patients from ticagrelor or
      prasugrel to clopidogrel is not recommended, if the patient is unable to adhere
      to long-term ticagrelor or prasugrel therapy, switching him/her to clopidogrel
      seems to be a reasonable practice to maintain chronic suppression of platelet
      aggregation and minimize the risk of ischemic events.

PMID- 29215419
TI  - Miscarriage.

PMID- 29215420
TI  - Interdisciplinary Guidelines for Care of Women Presenting to the Emergency
      Department With Pregnancy Loss.
AB  - In April 2016, the National Perinatal Association and Kaiser Permanente Northern
      California Nursing Research Community Benefits Grant sponsored an
      interdisciplinary summit to explore the needs of women who present with actual or
      potential pregnancy loss to the emergency department (ED). Thirty-two experts in
      the field of pregnancy loss, 17 of whom represented their professional
      organizations, participated. These experts, which included nurses, physicians,
      social workers, counselors, authors, and parents, worked together to create
      guidelines for care of women with a pregnancy loss in the ED. Recommendations for
      ED healthcare providers are included. Emergency department personnel agreed that
      improvements in care could be offered and were willing to endorse education for
      their staff. The guidelines delineate how to better provide physical, emotional,
      and bereavement support at any stage of gestational loss. Administrative support
      for policies in the ED is essential to ensure the delivery of family-centered,
      culturally sensitive practices when a pregnancy ends.

PMID- 29215421
TI  - Educating Emergency Department Nurses About Miscarriage.
AB  - Miscarriage is the unwanted ending of a pregnancy before 20 weeks gestation.
      Women experiencing miscarriage require specialized care from nurses and other
      healthcare professionals. Many women are dissatisfied with emergency care related
      to miscarriage and desire honest communication, validation of urgency, and more
      robust information at discharge. Perinatal bereavement education offers an
      opportunity for emergency department nurses to acquire specific knowledge and
      communication skills that assist with understanding the individualized experience
      of early pregnancy loss. For many women, a miscarriage is devastating, whereas
      for some, a part of life. Therefore, assessing the meaning of miscarriage is an
      essential step to providing sensitive, supportive care. Education was offered to
      emergency department nurses based on a 4-hour Resolve Through Sharing curriculum.
      Education focused on knowledge of policy and practice, medical aspects of
      pregnancy loss, information on how to assess the meaning of the miscarriage,
      respectful handling and disposition of the remains, and communication strategies
      to initiate and sustain a meaningful relationship with the woman and her family,
      within the barriers to care that are exclusive to the emergency department.
      Participants embraced the information and actively participated in dialogue of an
      evaluation process to identify needed revisions in current policies and practices
      for caring for this patient population. Recommendations and guidance for
      emergency room nurses who care for women experiencing miscarriage are offered.

PMID- 29215422
TI  - Maternity Nurses' Perceptions of Implementation of the Ten Steps to Successful
      Breastfeeding.
AB  - OBJECTIVE: The purpose of this study was to determine maternity nurses'
      perceptions of implementing the Ten Steps to Successful Breastfeeding. METHODS:
      An online survey and a focus group were used to evaluate perceptions of maternity
      nurses of implementing the Ten Steps to Successful Breastfeeding in an urban
      Texas hospital at the onset of the project initiation. Responses were transcribed
      and coded using Nvivo software. Thematic analysis was conducted and consensus was
      reached among the research team to validate themes. RESULTS: Twenty-eight
      maternity nurses participated. Nurses perceived a number of barriers to
      implementing the Ten Steps to Successful Breastfeeding including nurse staffing
      shortages, variations in practice among nurses, different levels of nurse
      education and knowledge about breastfeeding, lack of parental awareness and
      knowledge about breastfeeding, culture, and postpartum issues such as maternal
      fatigue, visitors, and routine required procedures during recovery care that
      interfered with skin-to-skin positioning. Maternity nurses desired more education
      about breastfeeding; specifically, a hands-on approach, rather than formal
      classroom instruction, to be able to promote successful implementation of the Ten
      Steps. CONCLUSIONS: More education on breastfeeding for new mothers, their
      families, and healthcare providers was recommended. Nurse staffing should be
      adequate to support nurses in their efforts to promote breastfeeding. Skin-to
      skin positioning should be integrated into the recovery period. Hospital
      leadership support for full implementation and policy adherence is essential.
      Challenges in implementing the Ten Steps were identified along with potential
      solutions.

PMID- 29215424
TI  - Intrapartum Management of Chorioamnionitis.

PMID- 29215423
TI  - GALT Deficiency Galactosemia.
AB  - Galactosemia is an inborn error of galactose metabolism that results from a
      deficiency in one of three enzymes, uridine diphosphate galactose 4'epimerase,
      galactokinase, or galactose-1-phosphate uridyltransferase (GALT). This article
      focuses on classical, clinical variant, and biochemical variant (Duarte)
      galactosemias caused by GALT enzyme deficiency. A brief overview of galactosemia
      and newborn screening is presented, followed by detailed information about each
      of the conditions. Confirmatory testing, acute and long-term management, and
      outcome for these galactosemia types are discussed as well as the importance of
      genetic counseling and testing for the infant and family to refine reproductive
      risk.

PMID- 29215425
TI  - Vegetarian Diet During Pregnancy: Making Sure Vitamin B12 Intake is Adequate.

PMID- 29215426
TI  - The Tragedy of Stillbirths Globally.

PMID- 29215427
TI  - 13 Reasons Why: A Trigger for Teen Suicide?

PMID- 29215429
TI  - Vaginal Seeding of Babies Born via Cesarean.

PMID- 29215431
TI  - GALT Deficiency Galactosemia.

PMID- 29215430
TI  - Clinical Aspects of Miscarriage.

PMID- 29215432
TI  - Western long-term accuracy of serum pepsinogen-based gastric cancer screening.
AB  - BACKGROUND: Even though mass gastric cancer screening is controversial in Western
      countries, diverse strategies have been proposed in intermediate-risk to high
      risk areas. AIM: The aim of this study was to determine the long-term accuracy of
      the pepsinogen test (PG) for early diagnosis of gastric cancer. PARTICIPANTS AND
      METHODS: A cohort of inhabitants from the Northern part of Portugal, aged between
      40 and 74 years (n=5913), subjected to the PG test (PGI<=70 ng/ml and
      PGI/PGII<=3), were followed up between November 2006 and December 2015. The
      diagnosis of gastric cancer was determined through linkage to the population
      based registry of cancer [North Region Cancer Registry of Portugal (RORENO)].
      RESULTS: Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among
      individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were
      'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6].
      Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of
      0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58%
      (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups
      was over 24 months. CONCLUSION: The PG test was found to be suboptimal as a
      screening test and, if used (before upper gastrointestinal endoscopy), it is
      mandatory to repeat it after 3 years.

PMID- 29215433
TI  - Gastritis staging as a clinical priority.
AB  - The elective background for gastric adenocarcinoma is the atrophic transformation
      of the gastric mucosa. The extent of mucosal atrophy basically parallels the risk
      of developing gastric cancer. This means that either noninvasive (serology) or
      invasive (endoscopy/histology) methods enabling the atrophic transformation to be
      quantified can be used theoretically to assess a given patient's gastric cancer
      risk. This review aims to focus on the reliability of histology gastritis
      Operative Link for Gastritis Assessment -staging system for assessing the
      'personalized' cancer risk in individuals with (atrophic) gastritis.

PMID- 29215434
TI  - Family planning in inflammatory bowel disease: childlessness and disease-related
      concerns among female patients.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) frequently affects women when family
      planning and pregnancy (FPP) are important issues. This survey aimed to identify
      patients with an increased need for medical counselling. PATIENTS AND METHODS: An
      internet-based questionnaire was offered to women with IBD. Characteristics in
      terms of FPP were analysed with respect to sociodemographic and disease-related
      factors. RESULTS: Childlessness was frequently reported (64.8% of 443
      participants). In women older than 35 years with IBD, childlessness was
      significantly more prevalent than that in the general population (36.7 vs. 22.9%,
      odds ratio=1.9, P<0.001). Overall, 44.2% of the women were satisfied with
      counselling in general, and only 27.3% with the specific advice on FPP. Women
      younger than 25 years were rarely satisfied with the advice in terms of FPP
      (18.2%) and demanded an intensified counselling (44.6%). Frequent concerns were
      the heritability of IBD (all women, 59.2%; mothers, 51.5%; childless, 62.5%,
      P<0.01), medication during FPP (44.7, 26.1, 52.4%, P<0.01) and miscarriage (38.9,
      16.8, 48.7%, P<0.01). CONCLUSION: The prevalence of childlessness in women with
      IBD compared with the general population increases with age. FPP-related worries,
      especially in terms of heredity, medication and miscarriage, are associated with
      an increased risk for childlessness. The results underline the importance of
      qualified counselling as early as possible during the course of the disase.

PMID- 29215436
TI  - Phosphoinositide 3-kinases and Diabetic Cardiomyopathy.

PMID- 29215435
TI  - Noninvasive fibrosis markers and chronic kidney disease among adults with
      nonalcoholic fatty liver in USA.
AB  - BACKGROUND/AIMS: Studies have shown that nonalcoholic fatty liver disease (NAFLD)
      is associated with an increased risk of chronic kidney disease (CKD). However, it
      is unknown whether severe liver fibrosis is associated with a higher prevalence
      of CKD among NAFLD. We examined the diagnostic performance of noninvasive
      fibrosis markers in identifying prevalent CKD among NAFLD. METHODS: This study
      represents an analysis of the National Health and Nutrition Examination Survey
      conducted in the USA between 1988 and 1994. NAFLD was defined by ultrasonographic
      evidence of hepatic steatosis without other liver diseases. CKD was defined by
      estimated glomerular filtration rate less than 60 ml/min/1.73 m. The presence and
      severity of hepatic fibrosis were determined by the NAFLD fibrosis score (NFS),
      FIB-4 score, APRI score, and BARD score. Multiple logistic regression was
      performed to generate odds ratios (ORs) and receiver operating characteristic
      curves were used to assess the predictive values of each marker. RESULTS: A total
      of 4142 individuals with NAFLD were included; 200 (4.8%) had CKD. The area under
      the receiver operating characteristic curves was 0.77, 0.75, 0.62, and 0.51 for
      the multivariable equation with FIB-4, NFS, BARD, and APRI score, respectively.
      Compared with patients with a low probability of developing advanced liver
      fibrosis, individuals with a high probability of developing fibrosis showed
      significantly increased odds of CKD as estimated by NFS (adjusted OR: 4.92, 95%
      confidence interval: 2.96-8.15) and FIB-4 (adjusted OR: 2.27, 95% confidence
      interval: 1.05-4.52). CONCLUSION: Advanced liver fibrosis, defined by NFS and FIB
      4 scores, is associated independently with CKD among individuals with NAFLD. FIB
      4 is the best predictor of an increased risk of prevalent CKD.

PMID- 29215437
TI  - Volumetric Analysis of 700 Mandibular Condyles Based Upon Cone Beam Computed
      Tomography.
AB  - The authors' aim was to provide volumetric data of mandibular condyles based upon
      cone beam computed tomography with the means of semiautomatic
      segmentation.Retrospective chart review of 350 patients (700 mandibular condyles)
      with cone beam computerized tomography between February 2007 and December 2016.
      Univariate analysis was performed to analyze associations between variables. P
      values <0.05 were considered significant. Volume measurement was performed in a
      semiautomatic segmentation method with the program "ITK-Snap."The mean volume was
      2.443 cm for the right condyle and 2.278 cm for the left condyle. Bivariate
      analysis indicated a highly significant difference between the volume of the left
      and right condyles (P < 0.01). Female had a significant smaller condyle volume
      than male (P < 0.01 left condyle; P < 0.01 right condyle). Volume and age did not
      significantly correlate (P = 0.939 right condyle; P = 0.798 left condyle).A
      detailed assessment of the volume of mandibular condyles with cone beam computed
      tomography can help to assess pathophysiological alterations.Hence, the
      volumetric measurement may improve patient's individualized treatment.

PMID- 29215438
TI  - Mucosal Dehiscence After Alveolar Bone Graft in Cleft.
AB  - Cleft lip and palate patient represent a challenging experience for the surgeon.
      This kind of patients had to be followed by a multidisciplinary team from the
      beginning to the end to avoid the deformation sequelae. During the several
      surgical procedures, the bone graft represents a possible procedure that, through
      the new procedure, could be avoided. Unfortunately, patient treated following the
      previous procedure must be submitted to alveolar bone graft to coordinate the
      arch, to restore the maxillary integrity, to allow the correct dentition.

PMID- 29215439
TI  - Age-Related Volumetric Changes in Mandibular Condyles.
AB  - A precise knowledge of the condylar changes with advancing age may improve
      understanding of pathophysiological alterations of the mandibular condyles.
      However, the majority of studies focusses on morphological changes, although
      volumetric analysis based upon cone beam computerized tomography may provide
      important additional data to characterize mandibular condyles. Therefore, we
      aimed to provide and compare volumetric data of mandibular condyles of a young
      and old patient group. This is a retrospective chart review of 195 patients with
      cone beam computerized tomography between 2007 and 2016. Student t test, analysis
      of variance, and Pearson correlation test were performed to analyze associations
      between categorical and continuous variables. P values <0.05 were considered as
      significant. Volume measurement was performed in a semiautomatic segmentation
      method with the program 'ITK-Snap.' Side- and sex-specific significant
      differences between condylar volumes were found both in the young and old patient
      cohort. Age and posterior occlusal support did not significantly correlate with
      the condylar volume. Volumetric measurement of the mandibular condyles may serve
      as an important additional characteristic, derived from 3-dimensional imaging.
      Significant differences in volumetric measurement of mandibular condyles exist
      between sex and side, but not in relation to age and occlusal support.

PMID- 29215440
TI  - The Aesthetic Analyzing of Midface Ratio After Folding Aponeurosis of Levator
      Palpebrae Superioris Muscle in the Ptosis Correction.
AB  - BACKGROUND: Some fordless-eyelid patients with moderate upper lid ptosis
      characterize in a higher eyebrow position which leads to an increased midfacial
      ratio. Apart from performing blepharoplasty to create dynamic folds, additional
      procedures such as folding aponeurosis of levator palpebrae superioris muscle
      were effective to revise the enlarged ratio of midface through lowering eyebrow,
      which gains good aesthetic results. However, the specific changes in the
      proportion of facial aesthetics and the importance of these change were serious
      lack in the literature as far as the authors know. PURPOSE: To measure the ratio
      of the length between upper edge of eyebrow and edge of lower eyelid (L1)/the
      length between edge of lower eyelid and nasal base (L2) in the fordless-eyelid
      and upper lid ptosis patients who received levator aponeurosis folding surgery,
      and to analyze the change in the proportion of midfacial aesthetics. METHOD: From
      December 2015 to October 2016, the pre- and postoperative photographs from 21
      cases of patients with foldless eyelid and upper lid ptosis who underwent the
      levator aponeurosis folding procedures in the authors' department were collected
      as study group. Additional full-face pictures of 20 Chinese female movie stars
      were prepared as control group. The ratios of L1/ L2 (J) were measured via Adobe
      Photoshop CS6. The statistical significance was analyzed and the change of
      midfacial proportion was evaluated. RESULT: In the study group, the mean value of
      preoperative L1/L2 (J1) is 0.746, and (J2) 0.657 postoperatively. In the control
      group, the mean value of L1/L2 (J3) is 0.667. Statistical differences showed
      between the pre- and postoperative samples and between preoperative samples and
      control group. There was no statistical difference between postoperative samples
      and control group samples. The ratios between L1 and L2 in postoperative samples
      are close to those in the control group, which are closer to the golden radio.
      CONCLUSION: Levator aponeurosis folding can effectively lower eyebrow in patients
      with upper lid ptosis, shortening the length between eyebrow and lower eyelid,
      and therefore harvesting a more appropriate and harmonious ratio of L1/ L2
      according to the golden section theory. The changes in the proportion of
      midfacial aesthetics after operation could be used as a key point in the
      preoperative communication and postoperative effect evaluation, besides the size
      of palpebral fissure and corneal exposure rate.

PMID- 29215441
TI  - Pierre Robin Sequence: An Evidence-Based Treatment Proposal.
AB  - BACKGROUND: The Pierre Robin sequence (PRS) has been defined as the presence of
      micrognathia, glossoptosis, and respiratory obstruction in the neonatal period.
      Since its original description, different therapeutic approaches have been
      proposed obtaining different success rates, but there is no consensus about its
      management. METHODS: A literature review was conducted in PubMed, Embase, and
      Cochrane databases, for the period of January,1985 to November, 2016. A number of
      23 articles resulting from clinical studies, discussing diagnostic tests or
      therapeutic approaches, and directly or indirectly comparing diagnostic or
      treatment modalities were selected and assessed using the GRADE methodology.
      RESULTS: After reviewing and analyzing the selected articles, an evidence-based
      algorithm for diagnosis and integral management of PRS patients was designed.
      CONCLUSION: Based on the anatomical principles and natural evolution of PRS, the
      clinical scenario must be evaluated thoroughly as a dynamic event to develop a
      management sequence that minimizes morbidity and mortality and accelerates
      patients' reinsertion to normal life.

PMID- 29215442
TI  - An Anatomic Morphological Study of Occipital Spurs in Human Skulls.
AB  - Occipital spurs are quite common; however, they are also the source of frequent
      discomfort to the patients. Their role has been implicated in causation of pain
      at the base of skull, which may extend to shoulder limiting the movement of the
      shoulder and neck. The present was carried out to find out the prevalence of
      occipital spur in human skull and to find out the anatomic morphological
      characteristics of occipital spur. A total of 30 cadaveric skulls were examined
      in the Department of Anatomy, Uttar Pradesh University of Medical Sciences, for
      the presence of occipital spur. These skulls were the part of boneset obtained as
      a part of undergraduate training in the department. All the measurements were
      taken using a digital Vernier Caliper after taking all necessary precaution to
      avoid any damage to these spurs. The prevalence of occipital spur in the present
      study was 10%. The mean width recorded in the present study was 13.40 mm (+/-6.7)
      and the mean length recorded was 13.45 mm (+/-1.05). Similarly, mean thickness
      noted was 2.43 mm (+/-0.43). Thus, the present study concludes that occipital
      spurs are the frequent source of discomfort to patients. The knowledge of this
      tubercle is of paramount importance to neurosurgeons, sports physicians, and
      radiologists for the diagnosis of such discomfort.

PMID- 29215443
TI  - Scaffold Free Bone Regeneration Using Platelet-Rich Fibrin in Calvarial Defect
      Model.
AB  - Bone regeneration is a complex process influenced by various physiological
      factors. Platelet-rich plasma (PRP) contains many growth factors and has shown
      osteogenic effects. The PRP is usually activated before use. However, the authors
      showed that nonactivated PRP (nPRP) and activated PRP have comparable osteogenic
      effects in the previous study. Generally, a scaffold has been needed for the
      application of PRP in the cranial defect model. In this study, the authors aimed
      to compare the performance of scaffold free platelet-rich fibrin (PRF) to nPRP as
      an adjuvant for bone regeneration.Twenty-four New Zealand White rabbits were
      randomly allocated into 3 groups: control, nPRP, and PRF. A 15 * 15 mm defect was
      created on each rabbit's cranium. Acellular collagen sponges (Gelfoam) were
      placed on the defects of the control group, Gelfoam with nPRP was used for the
      nPRP group, and PRF membrane was directly applied for the PRF group. nPRP and PRF
      were obtained from each subject's peripheral blood. Sixteen weeks later, the
      volume of regenerated bone was measured using 3-dimensional computed tomography.
      The surface area was measured via autopsy, and the samples were then obtained for
      histological analysis.Bone regeneration in the experimental groups was
      significantly greater than that in the control group. There were no significant
      differences in the area of regeneration or histological characteristics between
      the nPRP and PRF groups.In the calvarial defect of the rabbits, the use of PRF
      and scaffolded PRP showed comparable bone regeneration effects, which suggested
      that PRF might be a therapeutic alternative for bone grafts.

PMID- 29215444
TI  - Mandibular Reconstruction by Osteogenic Distraction Due to Two Different
      Injuries.
AB  - Varied factors, whether intrinsic or extrinsic, may lead to a decrease in the
      bone volume of the jaws. Trauma and pathology can be listed as examples of such
      factors. The aim of this study is to present the osteogenic distraction technique
      as alternative to augmentation of low mandibular bone volume caused by different
      etiologies. The first case reports a mandibular marginal resection of
      ameloblastoma and the second one reports a male patient presenting mandibular
      fracture sequelae. Both cases were treated according to the osteogenic
      distraction technique. Several factors have influence on the decision of
      treatment management of these conditions. Although autogenous bonegraft is
      considered criterion standard for alveolar reconstruction, its high rates of
      resorption and the morbidity associated to donor sites lead surgeons to seek for
      other surgical alternatives such as osteogenic distraction. Therefore, it also
      aims to expose the advantages and benefits of this technique as well as the
      satisfactory results achieved.

PMID- 29215445
TI  - Detailed Anatomy of Osteoperiosteal Ligamentous Structures in the Forehead.
AB  - This study aimed to present the anatomic characteristics of osteoperiosteal
      ligamentous attachments of the forehead and provide a better understanding of
      lateral eyebrow descent for safe and effective foreheadplasty. Anatomic
      dissections of the face were performed in 10 fresh Korean adult cadavers (20
      hemifaces) using 2.5* magnification surgical loupes. Supraorbital, inferomedial
      orbital, and frontonasal osteoperiosteal ligamentous attachments were identified
      as fibrous tissues originating from a bone, and their tensile strengths were
      measured. The supraorbital osteoperiosteal ligamentous attachment had medial and
      lateral parts. It can be classified into 4 subtypes. It was located 11.0 +/- 6.6
      mm lateral to the midline and 9.2 +/- 12.3 mm superior to the superior orbital
      margin. The inferomedial orbital osteoperiosteal ligamentous attachment was
      located 16.2 +/- 3.9 mm lateral to the midline and 2.2 +/- 2.7 mm inferior to the
      superior orbital margin, whereas the frontonasal osteoperiosteal ligamentous
      attachment was located 5.4 +/- 2.3 mm lateral to the midline and 1.4 +/- 8.5 mm
      superior to the superior orbital margin. Tensile strengths of all the
      osteoperiosteal ligamentous attachments in the forehead were above 10 N. These
      results indicate that osteoperiosteal ligamentous attachments develop in the
      rather medial region of the eyebrow and have a tensile strength adequate enough
      to maintain the medial eyebrow. Thus, the current study provides surgeons with
      detailed anatomic information that can be used as a valuable reference for
      forehead rejuvenation procedures.

PMID- 29215446
TI  - Nasal Septal Cavernous Hemangioma.
AB  - Hemangiomas are benign tumors originating from the skin, mucosa, muscle, gland,
      and vascular tissue in the bone. Although it is common in the head and neck
      region, it is rarely seen in the nasal cavity and paranasal sinuses.
      Histologically capillary, cavernous, and mixed types are present, the most common
      is cavernous-type hemangioma. Cavernous hemangiomas in the nasal cavity,
      generally originated from the lateral nasal wall, cause symptoms as nasal
      obstruction and epistaxis. In the author's patient, cavernous hemangioma was
      originated from the nasal septum, where rarely seen. The author wanted to discuss
      this rare disease by presenting a 78-year-old woman who presented with nasal
      obstruction and recurrent epistaxis to the author's clinic.

PMID- 29215447
TI  - Cross-Sectional Study of four Serological Bone Turnover Markers for the Risk
      Assessment of Medication-Related Osteonecrosis of the Jaw.
AB  - BACKGROUND: Despite the benefits related to the use of bisphosphonates and
      denosumab, medication-related osteonecrosis of the jaw (MRONJ) is a serious
      complication. The purpose of this study was to investigate the utility of 4
      biochemical markers including serum c-terminal telopeptide cross-link of type I
      collagen (s-CTX), serum osteocalcin (s-OC), serum parathormon (s-PTH), and serum
      bone-specific alkaline phosphatase (s-BAP) as useful clinical tools to help
      assess the risk for MRONJ prior to invasive oral surgery. MATERIALS AND METHODS:
      Twenty patients diagnosed with MRONJ and 20 controls who have been on
      antiresorptive therapies with no occurrence of MRONJ were included in this 2-arm
      cross-sectional study. The s-CTX, s-OC, s-PTH, and s-BAP values were measured.
      Mann-Whitney U test compared the s-CTX, s-OC, s-PTH, and s-BAP values of the
      MRONJ group and the controls (P < 0.05). RESULTS: Lower values were observed in
      the MRONJ group compared with the control group for s-CTX (130.00 pg/mL versus
      230.0 pg/mL; P = 0.12) and for s-OC (10.6 ng/mL versus 14.80 ng/mL; P = 0.051)
      both without significance and for s-BAP (0.23 MUkat/L versus 0.31 MUkat/L; P =
      0.002) with significance. By contrast, the median s-PTH value of the MRONJ group
      was higher (30.65 ng/L versus 25.50 ng/L; P = 0.89), but without significance.
      CONCLUSIONS: The evaluation of the 4 biochemical markers showed that only the
      value of s-BAP was significantly decreased in the MRONJ patients compared with
      the controls. Presently, because of the lack of evidence, a routine check prior
      to oral surgery for the risk assessment of MRONJ cannot be recommended.

PMID- 29215449
TI  - Seasonal Variation of Orofacial Clefts.
AB  - BACKGROUND: Orofacial clefts represent the most common craniofacial malformation
      diagnosed at birth and may be divided into isolated cleft lip (CL), cleft lip and
      palate (CL/P), or isolated cleft palate (CP). The causes of orofacial clefts have
      long been understood to be multifactorial; however, research into the genetic and
      environmental factors underpinning these disorders in African populations is
      scant. Seasonal variation in the occurrence of orofacial clefts was investigated.
      Seasonal variation is defined as differences due to periodic, temporal, and
      external influences, namely the particular time or season of the year. METHODS:
      The study design is a retrospective record review and sampled patients presenting
      to the Cleft Clinic at Charlotte Maxeke Johannesburg Academic Hospital during the
      time period October 2000 to October 2015. Ethical approval was obtained.
      Information recorded included patient demographics (date of birth and gender),
      diagnosis and laterality of the cleft. RESULTS: This study includes 512 infants.
      This study shows seasonal variation in the incidence of orofacial clefts limited
      to patients with both a CL/P. There was no significant seasonal variation
      observed in isolated CL or CP and laterality of the cleft. Significant seasonal
      variation was observed only in those born in winter versus summer, with more
      children born with a CL/P in winter months. CONCLUSION: Seasonal (or temporal)
      variation indicates a distinct environmental influence on the formation of
      orofacial clefts in utero, more specifically in pregnancies with the first
      trimester during spring. Several reasons have been advanced and include sunlight
      exposure and vitamin D levels, weight gain, and maternal obesity. More study is
      required to further elucidate these reasons.

PMID- 29215450
TI  - Tracing the Use of Cautery in the Modern Surgery.

PMID- 29215451
TI  - Mandibular Reconstruction Using a Customized Three-Dimensional Titanium Implant
      Applied on the Lingual Surface of the Mandible.
AB  - A patient had a right mandibular defect due to resection of an ameloblastoma.
      Previously, the defect had been reconstructed by an iliac bone graft, and
      subsequently, a titanium mesh with xenograft was used. However, it was not
      successfully reconstructed. For the recovery of mandible continuity and
      rehabilitation of jaw movement, we manufactured a customized 3-dimensional
      titanium implant by computer-aided design and manufacturing and electron beam
      melting technology. This implant was designed to have a porous body structure and
      lingual plate. The customized implant was accurately inserted in the bony defect.
      As a result, the patient showed a normal range of mouth opening and jaw movement.
      New bone migration was observed in the porous structure of the implant. Although
      there was a slight plate exposure and lack of alveolar bone formation, the
      customized 3D titanium implant successfully reconstructed the mandibular
      discontinuous defect and recovered jaw movement.

PMID- 29215453
TI  - Generalized Periodic Discharges With and Without Triphasic Morphology.
AB  - PURPOSE: Generalized periodic discharges (GPDs) with a triphasic morphology have
      been associated with nonepileptic encephalopathies. We conducted the study to
      assess the reliability in which electroencephalographers can differentiate
      triphasic from nontriphasic periodic discharges and to evaluate for the presence
      of electroencephalogram and clinical characteristics that are associated with a
      higher risk of seizures. METHODS: We studied prospectively 92 patients between
      May 2016 and February 2017. Each pattern was analyzed by two readers, who were
      blinded to clinical data. RESULTS: The interrater agreement was "substantial"
      (Kappa 0.67). The following features significantly increased the risk of
      developing seizures: the absence of triphasic morphology, focality on
      electroencephalogram, interburst suppression, a history of epilepsy, and an
      abnormal scan. The "GPD score" includes a history of epilepsy, focality on
      electroencephalogram, and the absence of triphasic morphology. A GPD score of 0
      has 13% risk of seizures, whereas a score of 5 to 6 has a 94% risk. CONCLUSIONS:
      Triphasic morphology GPDs confer less risk of seizures when compared with
      patients with GPDs without triphasic morphology. Features with a higher risk of
      seizures include focality on electroencephalogram, interburst suppression, a
      history of epilepsy, and an abnormal scan. The GPD score can be used to assess
      the risk of developing seizures in patients with GPDs.

PMID- 29215455
TI  - The Relationship Between Childhood Trauma and Poor Sleep Health in Adulthood.
AB  - OBJECTIVE: Childhood trauma has been related to adverse behavioral, mental, and
      health outcomes later in life. Sleep may be a potential mechanism through which
      childhood trauma is related to adverse health. The current retrospective study
      aimed to characterize the relationship between childhood trauma exposure and
      sleep health, a novel multidimensional measure of sleep. METHODS: Participants (N
      = 161; mean [standard deviation] age = 59.85 [9.06] years; 67.7% female)
      retrospectively reported trauma exposure using the Trauma History Questionnaire.
      Childhood trauma was defined as the number of reported traumatic events before 18
      years of age. Trauma exposure after 18 years of age and across the life-span was
      also recorded. Sleep health was derived both from diary- and actigraphy-assessed
      measures of sleep regularity, timing, efficiency, and duration, subjective sleep
      satisfaction, and daytime sleepiness from the Epworth Sleepiness Scale. The
      relationships between childhood trauma exposure and sleep health were examined
      using hierarchical linear regression, controlling for relevant covariates.
      RESULTS: In unadjusted models, a greater number of childhood trauma exposures
      were associated with poorer diary- and actigraphy-measured sleep health in
      adulthood. After adjustment for current stress, depression history, and other
      sociodemographic covariates, greater childhood trauma remained significantly
      associated with poorer sleep health (diary: beta = -0.20, DeltaR = 0.032;
      actigraphy: beta = -0.19, DeltaR = 0.027). Trauma exposure after 18 years of age
      and across the life-span did not relate to diary- or actigraphy-based sleep
      health. CONCLUSIONS: Childhood trauma may affect sleep health in adulthood. These
      findings align with the growing body of evidence linking childhood trauma to
      adverse health outcomes later in life.

PMID- 29215457
TI  - Associations of Positive Affect and Negative Affect With Allostatic Load: A
      Lifelines Cohort Study.
AB  - OBJECTIVE: Allostatic load (AL) reflects the deteriorating influences of stress
      on the body and comprises a selection of biological markers. AL is associated
      with negative life events, stress, and negative affect (NA), as well as poor
      health outcomes. However, whether AL is also associated with positive affect (PA)
      is not clear. The present study therefore explores the association between PA and
      AL, accounting for age, sex, NA, and health behaviors. METHODS: Data of 45,225
      individuals from the first wave of the multidisciplinary prospective population
      based cohort study Lifelines were used. AL was operationalized as the sum of 12
      inflammatory, cardiovascular, and metabolic markers. The association between PA
      and AL was tested in a cross-sectional study design using multiple linear
      regression analysis, adjusting for NA, confounders, and health behaviors. In
      addition, we explored whether the relation was moderated by age, sex, and NA.
      RESULTS: The AL profile was inversely associated with PA (B = -0.083, p < .001)
      when adjusted for NA, age, and sex. The association between AL and PA remained
      significant after adjusting for health behaviors (B = -0.076, p < .001). A
      significant moderating effect was found for sex (PA by sex: B = 0.046, p = .001),
      indicating that the association between PA and AL was stronger in women than in
      men. CONCLUSIONS: PA was associated with a more favorable AL profile, especially
      in women. These results add to the evidence that PA might be of relevance to the
      etiology of disease.

PMID- 29215456
TI  - Child and Adult Socioeconomic Status and the Cortisol Response to Acute Stress:
      Evidence From the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: A long-hypothesized pathway through which low socioeconomic status
      (SES) harms health is through dysregulation of the physiologic stress response
      systems. No previous studies have tested this hypothesis by investigating
      cortisol reactivity and recovery to acute stress in relation to SES at different
      times in the life course in adults. Alteration of the cortisol response to an
      acute stressor could signal dysregulation of the hypothalamic-pituitary-adrenal
      axis and has been associated with chronic illness. METHODS: We used data on 997
      adults 54 years or older from a multiethnic, multisite United States study to
      examine associations between life course SES and cortisol response to a
      laboratory stress challenge. Informed by life course theory, we hypothesized that
      lower child and adult SES would be associated with lower reactivity (i.e.,
      smaller increase in cortisol) and a slower recovery rate (i.e., slower rate of
      decline in cortisol after the challenge). RESULTS: In demographics-adjusted
      multilevel piecewise linear regression models, low child and adult SES were
      associated with a 19% (95% CI = 4%-50%) and 27% (7%-55%) slower recovery rate
      compared with high child and adult SES, respectively. Compared with participants
      with stable high SES, those with stable low SES had a 48% (16%-70%) slower
      recovery rate. Differences in reactivity by SES were small. CONCLUSIONS: Our
      results support the hypothesis that low SES throughout life affects the
      hypothalamic-pituitary-adrenal axis and in turn the ability to recover from
      exposure to acute stressors. This mechanism can help explain how socioeconomic
      disparities contribute to disparities in chronic disease.

PMID- 29215458
TI  - Recurrence of Renal Cell Cancer After Renal Transplantation in a Multicenter
      French Cohort.
AB  - BACKGROUND: Renal cancer accounts for 3% of adult malignancies; renal cell
      carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late
      recurrences. Recurrences after kidney transplantation are associated with a high
      mortality rate. We aimed to determine if recurrences are linked to tumor
      characteristics and to delays between diagnosis and transplantation. METHODS: We
      retrospectively analyzed data from French kidney-transplanted patients with
      medical histories of pretransplant renal cancer, focusing on the most common
      histological subtypes: clear cell and papillary cancers. Characteristics of the
      tumors, patients, and kidney transplantations were documented, and posttransplant
      patient survival was analyzed. RESULTS: Of 143 patients, 13 experienced cancer
      recurrence after kidney transplantation. The mean delay in recurrence was 3 +/-
      2.3 years posttransplantation, and the cumulative incidences of recurrence were
      7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in
      patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation
      between posttransplant recurrence and the interval before transplantation.
      Factors associated with a higher risk of cancer recurrence were histological
      clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P
      < 0.001). Recurrences were associated with a high mortality rate; 76.9% of
      patients with recurrences had died by the end of the follow-up period.
      CONCLUSIONS: Recurrences of clear cell RCC are not uncommon after kidney
      transplantation and are associated with very poor prognoses. These results should
      be considered before listing patients with a history of renal cancer for
      transplantation.

PMID- 29215460
TI  - Comparison of Preemptive Therapy and Antiviral Prophylaxis for Prevention of
      Cytomegalovirus in Seropositive Liver Transplant Recipients.
AB  - BACKGROUND: Few studies have directly compared preemptive therapy (PET) and
      antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in CMV
      seropositive (R+) orthotopic liver transplant (OLT) recipients. METHODS: We
      prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+
      OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral
      valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive
      negative weekly PCR results) and compared them with a historical cohort of 156 R+
      recipients who received AP (valganciclovir, 900 mg daily for 3 months). RESULTS:
      Patient characteristics were similar between PET and AP cohorts (P > 0.05 all
      comparisons). In the PET group, 24% (39/160) developed CMV viremia greater than
      250 IU/mL at a median of 42 (range, 7-93) days post-OLT. CMV monitoring adherence
      in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated
      PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV
      disease, acute allograft rejection, major infection, or death in the PET and AP
      cohorts was not significantly different: 2% versus 2%, 19% versus 16%, 10.5%
      versus 10.8%, and 5% versus 8%, respectively (P > 0.05 all comparisons). The
      estimated proportion of drug-exposed patients and average antiviral drug exposure
      were significantly lower with PET versus AP: 24% versus 100%, P < 0.001, and 15.8
      versus 81 g per patient, P < 0.001, respectively. CONCLUSIONS: PET is feasible in
      a nonresearch setting and is associated with similar CMV disease rates and other
      clinically relevant outcomes to AP in CMV seropositive liver transplant
      recipients.

PMID- 29215461
TI  - Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After
      Heart or Liver Transplantation.
AB  - BACKGROUND: Chronic kidney disease is common after heart or liver
      transplantation, with calcineurin inhibitors (CNI) considered the key
      contributor. A possible influence of posttransplant blood pressure has not been
      extensively examined. METHODS: Data from adult recipients of a first heart or
      liver transplant were analyzed regarding the relationship between blood pressure
      at year 1, renal function at year 5, and CNI therapy. RESULTS: Although we
      confirmed the well-known detrimental effect of increased 1-year systolic blood
      pressure on 5-year kidney graft survival, heart or liver graft survival was not
      affected. However, among 2534 heart transplant recipients with good renal
      function at year 1, increasing systolic blood pressure at year 1 was associated
      with higher rates of poor renal function at year 5 posttransplant. This
      association was confirmed on multivariate analysis overall (odds ratio, 1.25 per
      20 mm Hg increment; P < 0.001) and within subgroups. Similar results were
      observed in 1822 liver transplant recipients (odds ratio, 1.35; P < 0.001).
      Neither the type of CNI nor CNI dose or trough level at year 1 showed a
      significant association with kidney function at year 5. CONCLUSIONS: One-year
      blood pressure was identified as the major modifiable risk factor associated with
      deteriorating kidney function between years 1 and 5 after heart or liver
      transplantation.

PMID- 29215459
TI  - Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft
      Macrophages in a Rat Kidney Transplant Model.
AB  - BACKGROUND: Increasingly, it is being appreciated that B cells have broad roles
      beyond the humoral response and are able to contribute to and regulate
      inflammation. The specific role of B cells in the pathogenesis of early allograft
      inflammation remains unclear. METHODS: To address this question, we generated B
      cell-deficient (B) Lewis rats via clustered regularly interspaced short
      palindromic repeats (CRISPR) technology. In a full mismatch transplant model,
      kidneys from Brown Norway donors were transplanted into B Lewis recipients or
      wild type Lewis recipients. T cell-mediated rejection was attenuated with
      cyclosporine. RESULTS: Renal inflammation was reduced at 1 week after transplant
      (Banff scores for interstitial inflammation, microvascular inflammation,
      glomerulitis, and C4d) in allografts from B recipients. The reduction in
      interstitial inflammation was predominantly due to a decline in graft
      infiltrating macrophages. Intragraft T-cell numbers remained unchanged. In
      addition, B-cell deficiency was associated with increased T regulatory cells and
      reduced splenic T follicular helper cells at baseline; and significantly
      increased intragraft and splenic IL-10 mRNA levels after transplant. In vitro, B
      and wild type splenic T cells produced similar levels of IFN-gamma in response to
      T cell-specific activation. CONCLUSIONS: B-cell deficiency in this model produced
      an anti-inflammatory phenotype with a shift toward regulatory T-cell populations,
      production of anti-inflammatory cytokines (IL-10), and a reduction in allograft
      inflammation. These findings define a role for B cells to influence the cell
      populations and mediators involved in the pathogenesis of early allograft
      inflammation.

PMID- 29215462
TI  - Liver Transplantation in Cryptogenic Cirrhosis: Outcome Comparisons Between NASH,
      Alcoholic, and AIH Cirrhosis.
AB  - BACKGROUND: The outcomes of liver transplantation (LT) in patients with
      cryptogenic cirrhosis (CC) have not been adequately examined except for small
      case series. We believe that patients currently listed as CC have truly
      cryptogenic liver disease and may have different post-LT outcomes compared with
      nonalcoholic steatohepatitis (NASH). METHODS: We compared the post-LT outcomes of
      adults with CC (n = 3241) and compared them with cirrhosis from NASH (n = 4089),
      alcoholic cirrhosis (AC) (n = 7837), and autoimmune hepatitis (AIH) (n = 1435)
      using the United Network for Organ Sharing database from 2002 to 2016. We
      excluded those who had multiorgan transplantation and hepatocellular carcinoma.
      In addition to the well-known predictors of liver transplant outcomes, we
      analyzed the impact of Karnofsky Performance Status score at LT on immediate and
      late outcomes. RESULTS: There were significant differences in clinical
      characteristics between the groups. Despite these differences in clinical
      characteristics and risk factors, CC had similar graft and patient survival to
      NASH, AC, and AIH when assessed by Kaplan-Meier survival. Multivariate Cox
      regression analysis showed that graft and patient survival was similar in all 4
      groups after adjusting for other confounders. Hispanics had a 24% lower risk of
      death (hazard ratio, 0.76) compared with whites in these combined cohorts after
      adjusting for all risk factors. In addition to other known risk factors,
      Karnofsky Performance Status score of 30% or less was associated with a 33%
      increase in risk of death (hazard ratio, 1.33) on multivariate analysis.
      CONCLUSION: Patients with CC had similar graft and patient survival when compared
      with NASH, AC, and AIH cirrhosis.

PMID- 29215463
TI  - Variation in Practice Patterns for Listing Patients for Renal Transplantation in
      the United Kingdom: A National Survey.
AB  - BACKGROUND: Despite the availability of guidelines for the evaluation of
      candidates for renal transplantation, variation in access to transplantation
      exists. This national survey investigates whether center variation exists in the
      assessment of patients for renal transplantation in the United Kingdom. METHODS:
      An online survey, informed by qualitative interviews, was distributed to all UK
      renal centers. This survey examined center approaches to chronic kidney disease
      service provision, transplant recipient assessment, education provision, and
      waitlisting decision making processes. Center reevaluation policies for patients
      already listed and priorities for future development were also examined. RESULTS:
      All 71 renal centers responded. Of these, 83% reviewed predialysis patients in a
      low clearance clinic. In 26% of the centers, transplantation was not discussed as
      a treatment option with all patients. Fourteen centers reported having a
      dedicated transplant assessment clinic, whereas 28% did not have a formal
      assessment protocol. Age was an exclusion criterion for listing in 3 centers, all
      of which had a cutoff at 75 years. Eighty-three percent of the centers excluded
      patients with a high body mass index. Cardiac investigations were risk-stratified
      in 90% of centers. Surgical involvement varied with 11% of centers listing
      patients without formal surgical review. There was no formal protocol in place to
      reevaluate listed patients in 62% of centers. CONCLUSIONS: There is wide
      variation in UK practice patterns for listing patients for renal transplantation,
      though its impact on access to transplantation is unclear. The extent to which
      center-specific and patient-specific factors affect access to transplantation
      requires further analysis in a prospective cohort of patients.

PMID- 29215464
TI  - Difference in phase modulation of corticospinal excitability during the
      observation of the action of walking, with and without motor imagery.
AB  - The aim of the current study was to clarify how corticospinal excitability (CSE)
      is modulated during the observation of the action of walking, combined with motor
      imagery (MI). We examined the difference in phase modulation of CSE with and
      without MI during the observation of the action of walking. We measured motor
      evoked potentials in tibialis anterior and soleus muscles using transcranial
      magnetic stimulation under the following conditions: (1) baseline, (2) action
      observation (AO), and (3) AO and MI. Our results showed that, compared with AO
      alone, AO and MI of walking increased motor-evoked potentials. Our results
      suggest that CSE may be facilitated during AO and MI of walking, rather than
      during AO alone. Further, we postulated that AO and MI of walking may facilitate
      CSE in the tibialis anterior in a manner such as that evoked during actual
      walking.

PMID- 29215465
TI  - Expression of tissue inhibitor of metalloproteinases and matrix
      metalloproteinases in the ischemic brain of photothrombosis model mice.
AB  - Middle cerebral artery occlusion (MCAO) is the most widely used animal model of
      ischemic stroke. This model well recapitulates the pathological features of most
      human cases; however, MCAO is technically difficult to achieve in mice and has
      some disadvantages for investigating the molecular mechanisms of pathological
      progression in stroke. The recently developed photothrombosis model may be more
      suitable for research on the molecular mechanisms of ischemic stroke in mice.
      Yet, similarities and differences between the photothrombosis and MCAO models are
      not well characterized. In the present study, we examined the expression of
      tissue inhibitor of metalloproteinases (TIMPs) and matrix metalloproteinases
      (MMPs) in the brains of photothrombosis model mice. Our results indicated that
      the gene expression of TIMP-1 was upregulated in endothelial cells in the
      pathological area surrounding the infarction, similar to the MCAO model. Yet,
      pathologically induced changes in TIMP-1 were not affected by treatment with
      aspirin or etodolac. Whereas MMP-2 and MMP-8 mRNA were upregulated after
      infarction in both models, MMP-9 expression, which is induced in the infarct area
      in the MCAO model, was unchanged in the photothrombosis model. These findings
      suggest that the expression patterns of TIMP-1 and MMP-9 are regulated
      independently in photothrombosis model mice.

PMID- 29215466
TI  - Sensitivity of Takifugu TRPA1 to thermal stimulations analyzed in oocytes
      expression system.
AB  - Transient receptor potential ankyrin 1 (TRPA1s) from insects and several tetrapod
      vertebrates except rodents have been reported to be activated by high temperature
      with a relatively clear threshold. Our previous report, however, indicated that
      oocytes expressing zebrafish TRPA1b showed cold and heat-induced responses.
      Further, we also observed that zebrafish TRPA1b was gradually heat activated
      without a clear threshold. To study the possibility that these unique properties
      of thermal sensing of zebrafish TRPA1b are common to TRPA1s from other fish, we
      focused on the thermal response of pufferfish transient receptor potential
      ankyrin 1 (pfTRPA1) in the present study. By the two-electrode voltage clamp
      method using the Xenopus oocyte expression system, ionic currents were analyzed.
      Although some batches of pfTRPA1-expressing oocytes responded only to cold or
      heat stimulation, dual sensitivity to both cold and heat stimuli associated with
      pfTRPA1 expression was repeatedly observed. We detected a rapid response of
      oocytes expressing pfTRPA1 below 10 degrees C and also a gradual activation above
      25 degrees C without an apparent threshold. The results indicated that these
      thermal sensitivities of fish TRPA1 are clearly different from those of TRPA1s of
      tetrapod vertebrates.

PMID- 29215467
TI  - Cytosolic aspartate aminotransferase mediates the mitochondrial membrane
      potential and cell survival by maintaining the calcium homeostasis of BV2
      microglia.
AB  - Both mitochondrial aspartate aminotransferase (mAST) and cytosolic aspartate
      aminotransferase (cAST) are important components in the malate-aspartate shuttle 
      one of the two types of NADH shuttles in cells. A major goal of our current
      study was to determine specifically the roles of cAST in maintaining the [Ca]i,
      mitochondrial membrane potential and the survival of BV2 microglia by applying
      molecular approach to modulate the cAST levels. Our study found that decreased
      cAST by cAST siRNA can lead to significant increases in the [Ca]i, mitochondrial
      depolarization and apoptosis of BV2 microglia. The cAST siRNA-induced
      mitochondrial depolarization can be significantly attenuated by an inhibitor of
      calpain. We further found that the cAST siRNA-induced apoptosis can be prevented
      by the calpain inhibitor. Collectively, our study suggests that decreased cAST
      induces calpain activation by increasing the [Ca]i of BV2 microglia, resulting in
      mitochondrial depolarization and cell death. Moreover, our data suggest that
      decreased cAST may produce these pathological effects by malate-aspartate shuttle
      independent pathways.

PMID- 29215468
TI  - Task-based metabolic changes in the left dorsolateral prefrontal region during
      the letter N-back working memory task using proton magnetic resonance
      spectroscopy.
AB  - Neuroimaging and electrophysiological studies have consistently provided evidence
      on the role of dorsolateral prefrontal cortex in working memory. Recent studies
      have shown that the changes in metabolites in the brain could be detected upon
      functional activation using proton magnetic resonance spectroscopy. Therefore, we
      carried out a study in healthy control participants to understand the changes in
      metabolites during a letter N-back working memory task in the left dorsolateral
      prefrontal region. Single-voxel spectra were acquired from the left dorsolateral
      prefrontal region in 10 healthy control participants. The concentrations of
      metabolites were measured using a point-resolved spectroscopy sequence at three
      different time points, namely, before, during, and after the performance of the
      task. Repeated-measures analysis of variance indicated a main effect of time for
      glutamate concentrations and not for other metabolites. The healthy control
      participants showed a significant increase in glutamate concentrations during the
      performance of the letter N-back task. It was then followed by a significant
      decrease in the glutamate concentrations returning to the baseline after the
      task. The proposed method would be useful in understanding the dynamic changes in
      glutamate during the letter N-back task to examine the cognitive impairment in
      various neurodegenerative and psychiatric disorders.

PMID- 29215469
TI  - Multimodality coronary imaging to predict periprocedural myocardial necrosis
      after an elective percutaneous coronary intervention.
AB  - BACKGROUND: Although multiple imaging modalities have been tested to predict
      periprocedural myocardial necrosis (PMN), the superior predictive efficacy of
      these imaging findings has not been established fully. We sought to evaluate
      which findings of the coronary imaging tools would best provide predictive
      efficacy of PMN among optical coherence tomography (OCT), intravascular
      ultrasound (IVUS), and coronary computed tomography (CCT) angiography. PATIENTS
      AND METHODS: A total of 130 patients with stable angina pectoris who underwent
      OCT, IVUS, and CCT examinations for a single de-novo preprocedural lesion were
      investigated. PMN was defined on the basis of two different thresholds of cardiac
      troponin I (cTnI) elevation: moderate PMN [five times the upper reference limit
      (URL)<postpercutaneous coronary intervention peak cTnI level<20 times the URL]
      and major PMN (peak cTnI levels>20 times the URL). RESULTS: Moderate PMN and
      major PMN were observed in 25 (19.2%) and 10 (7.7%) patients, respectively.
      Multivariate logistic regression analysis identified four independent predictors
      of PMN (moderate PMN and major PMN): IVUS-defined echo-attenuated plaque (EAP),
      OCT-defined thin-cap fibroatheroma, OCT-defined plaque rupture, and CCT-defined
      low-attenuation plaque (P<0.05 for all variables). For major PMN, EAP length
      [odds ratio=1.80 (95% confidence interval: 1.20-2.69), P<0.01] and OCT minimum
      cap thickness [odds ratio=0.95 (95% confidence interval: 0.91-0.99), P<0.01] were
      identified as independent predictors. CONCLUSION: IVUS-derived EAP length and OCT
      minimum cap thickness were significant and specific predictors of major PMN among
      the examined multimodality plaque features, although all three modalities
      independently provided imaging findings of significant predictive efficacy for
      PMN more than five times the URL for cTnI.

PMID- 29215470
TI  - Invasive assessment of microvascular function in patients with valvular heart
      disease.
AB  - BACKGROUND: The aim of this study was to investigate microvascular function in
      patients with valvular heart disease (VHD), which causes chronic left ventricular
      volume and/or pressure overload, therefore change in coronary microvascular
      hemodynamics. PATIENTS AND METHODS: We prospectively enrolled 30 patients with
      VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and
      eight mitral regurgitation) and 30 controls. Intracoronary physiological
      assessments were performed in the unobstructed left anterior descending artery
      using a pressure-temperature sensor guidewire at rest and hyperemia. RESULTS: The
      index of microcirculatory resistance (IMR) was similar between the two groups
      (16.2+/-6.5 vs. 16.2+/-8.5, P=0.997), whereas coronary flow reserve (CFR) was
      lower in the VHD group compared with the controls (3.2+/-1.4 vs. 4.3+/-1.7,
      P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean
      transit time were similar between VHD and controls, whereas resting mean transit
      time was significantly shorter (0.70+/-0.29 vs. 0.89+/-0.39, P=0.035) and
      baseline resting microvascular resistance was significantly lower in the VHD
      group compared with the controls (58.1+/-25.4 vs. 78.1+/-36.7, P=0.011). Patients
      with aortic stenosis showed numerically higher IMR values than aortic
      regurgitation, mitral regurgitation, and controls, although this was not
      statistically significant (20.4+/-6.9, P=0.14). CFR was significantly correlated
      with log high-sensitivity cardiac troponin T levels in patients with VHD (r=
      0.523, P=0.004). CONCLUSION: CFR was reduced in patients with VHD compared with
      controls, despite similar microvascular function as assessed by IMR. This
      appeared to be mainly because of an increased resting coronary flow accompanied
      by a decreased resting coronary microvascular resistance rather than
      microvascular disease.

PMID- 29215471
TI  - Long-term outcomes of a recanalized thrombus treated with a paclitaxel-coated
      balloon: insights from optical coherence tomography.

PMID- 29215472
TI  - Intraplaque hemorrhage in a patient with acute coronary syndrome: insights from
      multimodality imaging.

PMID- 29215473
TI  - Duodenal Adenomas in Patients With Multiple Colorectal Adenomas Without Germline
      APC or MUTYH Mutations.
AB  - BACKGROUND: Patients with genetic adenomatous polyposis syndromes have an
      increased risk for duodenal cancer, and clear surveillance recommendations exist
      for this group. However, limited data are available on the duodenal phenotype of
      patients with multiple colorectal adenomas (10-99) without a germline APC or
      MUTYH mutation. OBJECTIVE: We aimed to assess the frequency, extent, and
      progression of duodenal adenomas in patients with multiple colorectal adenomas
      without a germline APC or MUTYH mutation. DESIGN: This was an historical cohort
      study. SETTINGS: This study was undertaken at 2 polyposis registries: the
      Academic Medical Center in the Netherlands, and St. Mark's Hospital in the United
      Kingdom. PATIENTS: We collected data on all patients with 10 to 99 colorectal
      adenomas and absent APC and MUTYH mutations, who underwent >=1
      esophagogastroduodenoscopy. MAIN OUTCOME MEASURES: The frequency, extent, and
      progression of duodenal adenomas were measured. Demographic and endoscopic data
      were collected, described, and compared between patients with and without
      duodenal adenomas. RESULTS: Eighty-three patients were identified, of which 8
      (9.6%) had duodenal adenomas, detected at a median of 58 years (range, 45-75 y).
      Duodenal adenomas were detected in 6 of 8 patients at first
      esophagogastroduodenoscopy. At diagnosis, all 8 patients had Spigelman stage I or
      II disease. Two of 5 patients with duodenal adenomas who underwent follow-up
      esophagogastroduodenoscopies increased to stage III disease. The other 3 remained
      stable. No one developed duodenal cancer. No differences in demographic and
      endoscopic data were found between patients with and without duodenal adenomas.
      LIMITATIONS: This study was limited by its retrospective design, selection bias,
      and small sample size. CONCLUSIONS: Duodenal adenomas are found in a minority of
      patients with multiple colorectal adenomas without a germline APC or MUTYH
      mutation, at an average age of 58 years, and, at diagnosis, disease severity is
      mild. These results are a first step in unraveling the duodenal phenotype of
      these patients, which is needed to provide appropriate upper GI screening and
      surveillance recommendations. See Video Abstract at
      http://links.lww.com/DCR/A357.

PMID- 29215474
TI  - Assessment of Ileostomy Output Using Telemedicine: A Feasibility Trial.
AB  - BACKGROUND: Ileostomies are a routine part of the care of patients with rectal
      cancer, but are associated with significant risk for dehydration, readmission,
      and acute kidney injury. Telemedicine has proven beneficial in decreasing
      readmission in chronic medical illnesses, but its utility in patients with an
      ileostomy is not well studied. OBJECTIVE: The purpose of this study was to
      evaluate the feasibility of televideoconferencing in the assessment of ileostomy
      output. DESIGN: An institutional review board-approved, prospective clinical
      trial was conducted at a single institution from November 2014 through December
      2015. SETTINGS: The study was conducted in a single, large academic medical
      center. PATIENTS: Patients >18 years of age undergoing surgery with plans for
      ileostomy were eligible. INTERVENTIONS: Televideoconference assessments of
      ileostomy output and the need for medical intervention were conducted during the
      postoperative stay and compared with in-person assessment. MAIN OUTCOME MEASURES:
      The primary end point of the trial was the feasibility of using teleconferencing
      to assess the need for medical intervention, defined as 90% agreement between
      telemedicine and in-person assessments. Secondary end points included
      patient/provider satisfaction, and correlative studies examined dehydration
      events and readmission. RESULTS: Twenty-seven patients underwent 44
      teleconferencing assessments of ileostomy output. Compared with in-person
      treatment decisions, there was a 95% match (95% CI, 85%-99%). The readmission
      rate for the study participants was 31%, and 18% experienced dehydration events.
      Both patients and faculty responded favorably to surveys regarding the use of
      telemedicine in the perioperative period. LIMITATIONS: The study is limited by
      its in-hospital use of technology and small sample size. CONCLUSIONS:
      Televideoconference evaluation is a feasible, reliable means of assessing
      ileostomy output with high patient and physician acceptance. Our pilot study
      provides rationale for further study in the postdischarge setting for patients
      with ileostomies. The incorporation of televideoconference assessment within a
      teledischarge program may enable early intervention to improve patient outcomes.
      See Video Abstract at http://links.lww.com/DCR/A455.

PMID- 29215475
TI  - An Effective Bundled Approach Reduces Surgical Site Infections in a High-Outlier
      Colorectal Unit.
AB  - BACKGROUND: Surgical site infections are the most common hospital-acquired
      infection after colorectal surgery, increasing morbidity, mortality, and hospital
      costs. OBJECTIVE: The purpose of this study was to investigate the impact of
      preventive measures on colorectal surgical site infection rates in a high-volume
      institution that performs inherent high-risk procedures. DESIGN: This was a
      prospective cohort study. SETTINGS: The study was conducted at a high-volume,
      specialized colorectal surgery department. PATIENTS: The Prospective Surgical
      Site Infection Prevention Bundle Project included 14 preoperative,
      intraoperative, and postoperative measures to reduce surgical site infection
      occurrence after colorectal surgery. Surgical site infections within 30 days of
      the index operation were examined for patients during the 1-year period after the
      surgical site infection prevention bundle was implemented. The data collection
      and outcomes for this period were compared with the year immediately before the
      implementation of bundle elements. All of the patients who underwent elective
      colorectal surgery by a total of 17 surgeons were included. The following
      procedures were excluded from the analysis to obtain a homogeneous patient
      population: ileostomy closure and anorectal and enterocutaneous fistula repair.
      MAIN OUTCOME MEASURES: Surgical site infection occurring within 30 days of the
      index operation was measured. Surgical site infection-related outcomes after
      implementation of the bundle (bundle February 2014 to February 2015) were
      compared with same period a year before the implementation of bundle elements
      (prebundle February 2013 to February 2014). RESULTS: Between 2013 and 2015, 2250
      abdominal colorectal surgical procedures were performed, including 986 (43.8%)
      during the prebundle period and 1264 (56.2%) after the bundle project. Patient
      characteristics and comorbidities were similar in both periods. Compliance with
      preventive measures ranged between 75% and 99% during the bundle period. The
      overall surgical site infection rate decreased from 11.8% prebundle to 6.6% at
      the bundle period (P < 0.001). Although a decrease for all types of surgical site
      infections was observed after the bundle implementation, a significant reduction
      was achieved in the organ-space subgroup (5.5%-1.7%; P < 0.001). LIMITATION: We
      were unable to predict the specific contributions the constituent bundle
      interventions made to the surgical site infection reduction. CONCLUSIONS: The
      prospective Surgical Site Infection Prevention Bundle Project resulted in a
      substantial decline in surgical site infection rates in our department.
      Collaborative and enduring efforts among multiple providers are critical to
      achieve a sustained reduction See Video Abstract at
      http://links.lww.com/DCR/A438.

PMID- 29215476
TI  - Clinical Outcomes of Self-Expandable Metal Stents for Malignant Rectal
      Obstruction.
AB  - BACKGROUND: Self-expandable metal stents are widely used to treat malignant
      colorectal obstruction. However, data on clinical outcomes of stent placement for
      rectal obstruction specifically are lacking. OBJECTIVE: We aimed to investigate
      the clinical outcomes of self-expandable metal stents in malignant rectal
      obstruction in comparison with those in left colonic obstruction and to identify
      factors associated with clinical failure and complication. DESIGN: This was a
      retrospective study. SETTINGS: The study was conducted at a tertiary care center.
      PATIENTS: Between January 2005 and December 2013, medical charts of patients who
      underwent stent placement for malignant rectal or left colonic obstruction were
      reviewed retrospectively. INTERVENTION: Study intervention included self
      expandable metal stent placement. MAIN OUTCOME MEASURES: Technical success,
      clinical success, and complications were measured. RESULTS: Technical success
      rates for the 2 study groups (rectum vs left colon, 93.5% vs 93.1%; p = 0.86) did
      not differ significantly; however, the clinical success rate was lower in
      patients with rectal obstruction (85.4% vs 92.1%; p = 0.02). In addition, the
      complication rate was higher in patients with rectal obstruction (37.4% vs 25.1%;
      p = 0.01). Patients with rectal obstruction showed higher rates of obstruction
      because of extracolonic malignancy (33.8% vs 15.8%; p < 0.001) and stent use for
      palliation (78.6% vs 56.3%; p < 0.001). Multivariate analysis indicated
      obstruction attributed to extracolonic malignancy and covered stent usage to be
      independent risk factors for clinical failure. Factors predictive of
      complications in the palliative group were total obstruction, obstruction because
      of extracolonic malignancy, and covered stent usage. LIMITATIONS: This was a
      retrospective, single-center study. CONCLUSIONS: The efficacy and safety of stent
      placement for malignant rectal obstruction were comparable with those for left
      colonic obstruction. However, obstruction attributed to extracolonic malignancy,
      use of covered stents, and total obstruction negatively impacted clinical
      outcomes of self-expandable metal stent placement and must be considered by
      endoscopists. See Video Abstract at http://links.lww.com/DCR/A417.

PMID- 29215477
TI  - Prophylactic Ureteral Catheters for Colectomy: A National Surgical Quality
      Improvement Program-Based Analysis.
AB  - BACKGROUND: Despite improvement in technique and technology, using prophylactic
      ureteral catheters to avoid iatrogenic ureteral injury during colectomy remains
      controversial. OBJECTIVE: The aim of this study was to evaluate outcomes and
      costs attributable to prophylactic ureteral catheters with colectomy. DESIGN:
      This was a retrospective study. SETTINGS: The study was conducted at a single
      tertiary care center. PATIENTS: The colectomy-targeted American College of
      Surgeons National Surgical Quality Improvement Program database from 2012 to 2014
      was queried. MAIN OUTCOME MEASURES: The primary end point was the rate of 30-day
      ureteral injury after colectomy. Univariate and multivariate analyses determined
      factors associated with ureteral injury and urinary tract infection in patients
      undergoing colectomy. RESULTS: A total of 51,125 patients were identified with a
      mean age of 60.9 +/- 14.9 years and a BMI of 28.4 +/- 6.7 k/m; 4.90% (n = 2486)
      of colectomies were performed with prophylactic catheters, and 333 ureteral
      injuries (0.65%) were identified. Prophylactic ureteral catheters were most
      commonly used for diverticular disease (42.2%; n = 1048), with injury occurring
      most often during colectomy for diverticular disease (36.0%; n = 120). Univariate
      analysis of outcomes demonstrated higher rates of ileus, wound infection, urinary
      tract infection, urinary tract infection as reason for readmission, superficial
      site infection, and 30-day readmission in patients with prophylactic ureteral
      catheter placement. On multivariate analysis, prophylactic ureteral catheter
      placement was associated with a lower rate of ureteral injury (OR = 0.45 (95% CI,
      0.25-0.81)). LIMITATIONS: This was a retrospective study using a clinical data
      set. CONCLUSIONS: Here, prophylactic ureteral catheters were used in 4.9% of
      colectomies and most commonly for diverticulitis. On multivariate analysis,
      prophylactic catheter placement was associated with a lower rate of ureteral
      injury. Additional research is needed to delineate patient populations most
      likely to benefit from prophylactic ureteral stent placement. See Video Abstract
      at http://links.lww.com/DCR/A482.

PMID- 29215478
TI  - Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical
      Trial.
AB  - BACKGROUND: Lower GI hemorrhage is a common source of morbidity and mortality.
      Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss
      in a variety of clinical conditions. Information regarding the use of tranexamic
      acid in treating lower GI hemorrhage is lacking. OBJECTIVE: The aim of this trial
      was to determine the clinical efficacy of tranexamic acid when used for lower GI
      hemorrhage. DESIGN: This was a prospective, double-blind, placebo-controlled,
      randomized clinical trial. SETTINGS: The study was conducted at a tertiary
      referral university hospital in Australia. PATIENTS: Consecutive patients aged
      >18 years with lower GI hemorrhage requiring hospital admission from November
      2011 to January 2014 were screened for trial eligibility (N = 265).
      INTERVENTIONS: A total of 100 patients were recruited after exclusions and were
      randomly assigned 1:1 to either tranexamic acid or placebo. MAIN OUTCOME
      MEASURES: The primary outcome was blood loss as determined by reduction in
      hemoglobin levels. The secondary outcomes were transfusion rates, transfusion
      volume, intervention rates for bleeding, length of hospital stay, readmission,
      and complication rates. RESULTS: There was no difference between groups with
      respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p =
      0.9445). There was no difference with respect to transfusion rates (14/49
      tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs
      1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of
      hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No
      complications occurred as a direct result of tranexamic acid use. LIMITATIONS: A
      larger multicenter trial may be required to determine whether there are more
      subtle advantages with tranexamic acid use in some of the secondary outcomes.
      CONCLUSIONS: Tranexamic acid does not appear to decrease blood loss or improve
      clinical outcomes in patients presenting with lower GI hemorrhage in the context
      of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

PMID- 29215479
TI  - Major Abdominal and Perianal Surgery in Crohn's Disease: Long-term Follow-up of
      Australian Patients With Crohn's Disease.
AB  - BACKGROUND: Most patients with Crohn's disease still require surgery despite
      significant advances in medical therapy, surveillance, and management strategies.
      OBJECTIVE: The purpose of this study was to assess surgical strategies and
      outcomes in Crohn's disease, including surgical recurrence and emergency surgery.
      DESIGN: This was a multicenter, retrospective review of a prospectively collected
      database. SETTINGS: A specialist-referred cohort of patients with Crohn's disease
      between 1970 and 2009 was studied. PATIENTS: Included were 972 patients with
      Crohn's disease who were referred to the Sydney Inflammatory Bowel Disease cohort
      database. MAIN OUTCOME MEASURES: Main outcomes of interest were the rates of
      major abdominal and perianal surgery between decades (1970-1979, 1980-1989, 1990
      1999, and 2000-2009), indications for surgery, types of procedure performed, rate
      of elective and emergency surgery, risk of surgical recurrence, and predictive
      factors for surgery. RESULTS: Between 1970 and 2009, the overall risks of surgery
      within 5, 10, and 15 years of diagnosis were 31.7%, 43.3%, and 48.4%. The median
      time to first surgery from time of diagnosis was 2 years (range, 0-31 years). A
      total of 6.7% of patients required emergency surgery within 5 years of diagnosis.
      In total, 8.8% of patients required emergency surgery within 15 years. The
      overall risk of surgical recurrence was 35.9%. The risk of major abdominal
      surgery significantly decreased between 2000 and 2009 when compared with the 1970
      to 1979 period (OR = 0.49 (95% CI, 0.34-0.70). However, the rate of perianal
      surgery significantly increased (OR = 5.76 (95% CI, 2.54-13.06)). The main
      indications for surgery were enteric stricture or obstruction, perianal disease,
      and intra-abdominal fistulas/abscess. Of the 972 patients over 4 decades, only 11
      patients (1.1%) were diagnosed with colorectal cancer. LIMITATIONS: This was a
      specialist-referred cohort, not a population-based study. CONCLUSIONS: The rate
      of major abdominal surgery has decreased, with surgery reserved for more severe
      and complicated disease. The natural history of patients with more complicated
      Crohn's disease and severe phenotypes puts them at higher risk of surgical
      recurrence and emergency surgery. There has been no reduction in emergency
      surgery rates and there has been an increase in surgical recurrence despite the
      reduction in surgical rate morbidity. See Video Abstract at
      http://links.lww.com/DCR/A483.

PMID- 29215480
TI  - Optimal Surveillance Protocols After Curative Resection in Patients With Stage IV
      Colorectal Cancer: A Multicenter Retrospective Study.
AB  - BACKGROUND: After patients with stage IV colorectal cancer undergo curative
      surgical resection, there is a large risk for recurrence. To establish optimal
      surveillance guidelines, an understanding of the temporal risk factors for
      recurrence is necessary. OBJECTIVE: The primary aim of our study was to determine
      predictors for early (within 1 year), middle (1-2 years), and late (2 years or
      later) recurrence following curative resection in patients with stage IV
      colorectal cancer. DESIGN: This was a retrospective cohort study. SETTINGS: The
      study was conducted at multiple institutions. PATIENTS: The retrospective cohort
      study comprised 1070 patients with stage IV colorectal cancer after an R0
      resection for the primary and metastatic lesions in 19 institutions from January
      1997 to December 2007. MAIN OUTCOME MEASURES: Risk factors for early, middle, and
      late recurrence were determined by logistic regression and Cox proportional
      hazards models. RESULTS: The overall recurrence rate was 73% (784/1070). Cancer
      specific survival was 29.5 months, and recurrence-free survival was 8.9 months.
      Early recurrence occurred in 488 (62%), middle recurrence in 184 (24%), and late
      recurrence in 112 (14%). In multivariable analysis, early recurrence risk factors
      included rectum site, depth of tumor invasion (T4), increasing N-staging, venous
      invasion, and liver metastasis. Late recurrence risk factors were tumor size <=50
      mm, and peritoneal dissemination. LIMITATIONS: Because of the retrospective
      nature of this study, postoperative therapy was not standardized. CONCLUSIONS:
      Risk factors differ for early, middle, and late recurrences of stage IV
      colorectal cancer following curative resection. Early (within 1 year) recurrence
      factors were rectum site, T4, N-staging, venous invasion, and liver metastasis,
      whereas late (2 years or later) recurrence risk factors were small tumor size and
      peritoneal dissemination. Our study provides important data to guide a
      surveillance protocol following stage IV colorectal cancer curative resection.
      See Video Abstract at http://links.lww.com/DCR/A460.

PMID- 29215481
TI  - Trends in Surgeon-Level Utilization of Sacral Nerve Stimulator Implantation for
      Fecal Incontinence in New York State.
AB  - BACKGROUND: There is a paucity of real-world data regarding surgeon utilization
      of sacral nerve stimulation for fecal incontinence compared with anal
      sphincteroplasty. OBJECTIVE: This study aims to examine trends in sacral nerve
      stimulation use compared with sphincteroplasty for fecal incontinence and surgeon
      level variation in progression to implantation of the pulse generator. DESIGN:
      This is a population-based study. PATIENTS: Patients with fecal incontinence
      between 2011 and 2014 in New York who underwent stage 1 of the sacral nerve
      stimulation procedure were selected. For the comparison with sphincteroplasty,
      patients with fecal incontinence who underwent anal sphincteroplasty between 2008
      and 2014 were included. MAIN OUTCOME MEASURES: The main outcomes after sacral
      nerve stimulation generator placement were unplanned 30-day admission, emergency
      department visit within 30 days, revision or explant of leads or generator, and
      30-day mortality. RESULTS: Six hundred twenty-one patients with fecal
      incontinence underwent a stage 1 procedure with 79.7% progressing to stage 2.
      There has been an increase in the number of sacral nerve stimulation cases per
      year as well as the number of surgeons performing the procedure. The rate of
      progression to stage 2 among patients treated by colorectal surgeons was 80.2%
      compared with 77.0% among those treated by noncolorectal surgeons. Among those
      who completed stage 2, there were 3 (0.5%) unplanned 30-day admissions, 24 (4.4%)
      emergency department visits within 30 days, and 0 mortalities within 30 days.
      Thirty-two (6.5%) patients had their leads or pulse generator revised or
      explanted. There was a significant decrease in annual sphincteroplasty cases and
      the number of providers performing the procedure starting in 2011. LIMITATIONS:
      We lacked data regarding patient and physician decision making and the severity
      of disease. CONCLUSIONS: Sacral nerve stimulation for fecal incontinence is
      increasing in popularity with an increasing number of surgeons utilizing sacral
      nerve stimulation for fecal incontinence rather than sphincteroplasty. See Video
      Abstract at http://links.lww.com/DCR/A450.

PMID- 29215482
TI  - Association of Telomere Length With Chromosomal Damage Among Chinese Workers
      Exposed to Vinyl Chloride Monomer.
AB  - OBJECTIVE: To explore the relationship between relative telomere length (RTL) and
      chromosomal damage represented by micronucleus (MN) frequencies among vinyl
      chloride monomer (VCM) -exposed workers. METHODS: A group of 126 VCM-exposed
      workers, 60 internal controls, and 25 external controls were examined for RTL by
      Quantitative polymerase chain reaction and MN frequencies by cytokinesis-block
      micronucleus test. Cumulative exposure dose was used to estimate the exposure of
      VCM-exposed workers. RESULTS: The RTL were significantly shorter in exposed
      workers and internal controls than in external controls. The exposed workers had
      significantly increased MN frequencies than both control groups. Additionally, MN
      frequencies were negatively associated with RTL in VCM-exposed group.
      CONCLUSIONS: VCM exposure may alter telomere length, which could be a potential
      biomarker of susceptibility to chromosomal damage.

PMID- 29215483
TI  - Mortality Among Hardmetal Production Workers: The Swedish Cohort.
AB  - BACKGROUND: The mortality pattern was determined in a cohort of 16,999 white and
      blue-collar workers in the Swedish hardmetal industry, particularly for cobalt
      exposure and lung cancer. METHODS: The mortality follow-up analysis in the
      Swedish Mortality register covered the period from 1952 to 2012. The exposure
      measures were ever/never exposed, duration of exposure, cumulative, and mean
      cobalt concentrations. RESULTS: The mortality of all causes was significantly
      increased, highly associated with the short-term employed workers. A negative
      exposure-response was found for lung cancer and duration of exposure. An exposure
      response was determined for cumulative and mean cobalt exposures analyzed by
      quartiles, but not for exposure classes. Internal comparison analysis using
      proportional hazard showed no exposure-response. CONCLUSIONS: The cohort lung
      cancer mortality showed no correlation to cobalt, nickel, or tungsten exposure.

PMID- 29215484
TI  - Mortality Among Hardmetal Production Workers: German Historical Cohort Study.
AB  - OBJECTIVE: The aim of this study was to investigate a cohort in German hardmetal
      industry, especially relationship between exposures to cobalt, with and without
      tungsten, and risks of total and cause-specific mortality. METHODS: The cohort
      comprises blue-collar workers at three German plants who were employed in
      hardmetal processing. Individual cumulative exposures and long-term average
      concentrations were estimated for cobalt, nickel, tungsten, respirable, and
      inhalable dust. Standardized mortality ratios (SMRs) were calculated for external
      comparisons. Time-dependent multivariable Cox models were performed for internal
      analyses. RESULTS: Elevated SMRs were found for all-cause, heart diseases, and
      nonmalignant respiratory diseases mortality, but not for lung cancer. Internal
      analyses did not show increased risks for any endpoints, and no exposure-response
      relationship was indicated. CONCLUSIONS: This study does not provide evidence for
      elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of
      death causes in particular, impede conclusions about exposure effects.

PMID- 29215485
TI  - Mortality Among Hardmetal Production Workers: US Cohort and Nested Case-Control
      Studies.
AB  - OBJECTIVES: To evaluate total and cause-specific mortality among hardmetal
      production workers with emphasis on lung cancer. METHODS: Subjects were 7304
      workers ever employed in one of eight US plants from 1952 to 2008. Vital status
      through 2012 was determined for 97% of subjects and cause of death for 98.3% of
      1087 deaths. We computed standardized mortality ratios (SMRs) and evaluated
      exposure-response via relative risk regression analysis. RESULTS: We observed
      overall deficits in deaths for total mortality, all cancers, and lung cancer and
      found no evidence of any exposure-response relationships for lung cancer.
      CONCLUSIONS: We found no evidence that exposure to tungsten, cobalt, or nickel,
      at levels experienced by the workers examined, increases lung cancer mortality
      risks. We also found no evidence that work in the US hardmetal industry increases
      mortality risks from any other causes of death.

PMID- 29215486
TI  - Mortality Among Hardmetal Production Workers: Swedish Measurement Data and
      Exposure Assessment.
AB  - BACKGROUND: Mortality pattern was determined in a cohort of 16,999 white and blue
      collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt
      is presented. METHODS: A historical database (1970 to 2012) of personal and area
      measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry
      was created. Log linear and exponential modeling of cobalt concentrations based
      on time period, job, and site was performed, and cumulative and mean exposures
      were calculated. RESULTS: Some 37% of the personal cobalt measurements exceeded
      0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear
      regression showed statistical differences (P < 0.05) between sites, time periods,
      and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers
      exceeded 0.4 mg/m years. CONCLUSION: Low levels of cumulative and mean exposures
      were determined.

PMID- 29215487
TI  - Mortality Among Hardmetal Production Workers: Pooled Analysis of Cohort Data From
      an International Investigation.
AB  - OBJECTIVES: Based on a pooled analysis of data from an international study,
      evaluate total and cause-specific mortality among hardmetal production workers
      with emphasis on lung cancer. METHODS: Study members were 32,354 workers from
      three companies and 17 manufacturing sites in five countries. We computed
      standardized mortality ratios and evaluated exposure-response via relative risk
      regression analysis. RESULTS: Among long-term workers, we observed overall
      deficits or slight excesses in deaths for total mortality, all cancers, and lung
      cancer and found no evidence of any exposure-response relationships for lung
      cancer. CONCLUSIONS: We found no evidence that duration, average intensity, or
      cumulative exposure to tungsten, cobalt, or nickel, at levels experienced by the
      workers examined, increases lung cancer mortality risks. We also found no
      evidence that work in these facilities increased mortality risks from any other
      causes of death.

PMID- 29215489
TI  - Withdrawal of Advanced Notice of Proposed Rulemaking (ANPRM) on Obstructive Sleep
      Apnea (OSA) Does Not Mean Examiners and Employers Should Ignore Safety Risks.

PMID- 29215488
TI  - Cancer Incidence Among Hardmetal Production Workers: The Swedish Cohort.
AB  - : The cancer incidence was determined for 3713 workers from three plants from
      1958 to 2011. The exposure measures were ever/never exposed, duration,
      cumulative, and mean cobalt concentrations.The incidence of all malignant
      neoplasms was increased at one plant, but standardized incidence ratio (SIR) was
      0.96 for all workers. Lung cancer incidence was increased for all workers, SIR
      1.38 (1.01 to 1.85). The lung cancer incidence was associated with shorter
      employment time and showed no exposure-response. There was decreased incidence
      for skin cancer. Increased lip cancer incidence found at one of the production
      plants might be related to diagnostic intensity.Lung cancer incidence showed no
      correlation to cobalt exposure based on internal comparison. The increased SIR
      for all workers might be associated with other factors.

PMID- 29215492
TI  - Postoperative Opioid Use, Complications, and Costs in Surgical Management of
      Lumbar Spondylolisthesis.
AB  - STUDY DESIGN: Retrospective analysis on a national longitudinal database (2007
      2014). OBJECTIVE: To determine the association between arthrodesis and
      complication rates, costs, surgical revision, and postoperative opioid
      prescription. SUMMARY OF BACKGROUND DATA: Arthrodesis in patients receiving
      laminectomy for lumbar spondylolisthesis remains controversial. However,
      population-level evidence to support the use of arthrodesis remains limited.
      METHODS: We identified 73,176 patient records and used coarsened exact matching
      to create comparable populations of patients who received laminectomy or
      laminectomy with arthrodesis. We use linear and logistic regression models to
      analyze the relationship between arthrodesis and postoperative complications,
      length of stay, costs, readmissions, surgical revisions, and postoperative opioid
      prescribing. RESULTS: Patients who underwent arthrodesis spent 1 more day in the
      hospital on average (P < 0.01), and had higher costs of care at their index visit
      ($24,126, P < 0.01), which were partially offset by lower costs of care over the
      2 years following their procedure ($14,667 less in arthrodesis patients, P =
      0.01). Patients with arthrodesis were less likely to have a surgical revision
      (odds ratio = 0.66, P < 0.01). Patients with arthrodesis used more opioids in the
      first 2 months following their procedure, but had comparable opioid use to
      patients undergoing laminectomy without arthrodesis in all other postoperative
      months over the next 2 years, and were not more or less likely to convert to
      chronic opioid use. Postoperative opioid prescription varied dramatically across
      states (P < 0.01); geographic variation in opioid use is substantially greater
      than differences in opioid use based on procedure performed. CONCLUSION:
      Arthrodesis is associated with reduced likelihood of surgical revision and
      increased use of opioids in the first 2 months following surgery, but not
      associated with greater or lesser opioid use beyond the initial 2 postoperative
      months. Geographic variation in opioid use is substantial even after accounting
      for patient characteristics and for whether patients underwent arthrodesis. LEVEL
      OF EVIDENCE: 3.

PMID- 29215493
TI  - Minimally Invasive Lateral Lumbar Interbody Fusion for Adult Spinal Deformity:
      Clinical and Radiological Efficacy With Minimum Two Years Follow-up.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To evaluate the clinical
      and radiological efficacies of supplementing minimally invasive lateral lumbar
      interbody fusion (LLIF) with open posterior spinal fusion (PSF) in adult spinal
      deformity (ASD). SUMMARY OF BACKGROUND DATA: Minimally invasive techniques have
      been increasingly applied for surgery of ASD. Few reports have been published
      that directly compare LLIF combined with PSF to conventional PSF for ASD.
      METHODS: To evaluate the advantages of minimally invasive LLIF for ASD, patients
      who underwent minimally invasive LLIF followed by open PSF (combined group) were
      compared with patients who only underwent PSF (only PSF group). The clinical and
      radiological outcomes for deformity correction and indirect decompression were
      assessed. The occurrence of proximal junctional kyphosis (PJK) and proximal
      junctional failure (PJF) were also evaluated. RESULTS: No significant differences
      were observed in the clinical outcomes of the Oswestry Disability Index (ODI),
      visual analog scale, and major complications including reoperations between the
      groups. No additional advantage was found for coronal deformity correction, but
      the restoration of lumbar lordosis in the combined group was significantly higher
      postoperatively (15.3 degrees  vs. 8.87 degrees , P = 0.003) and last follow-up
      (6.69 degrees  vs. 1.02 degrees , P = 0.029) compared to that of the only PSF
      group. In the subgroup analysis for indirect decompression for the combined
      group, a significant increase of canal area (104 vs. 122 mm) and foraminal height
      (16.2 vs. 18.5 mm) was noted. The occurrence of PJK or PJF was significantly
      higher in the combined group than in the only PSF group (P = 0.039). CONCLUSION:
      LLIF has advantages of indirect decompression and greater improvements of
      sagittal correction compared to only posterior surgery. LLIF should be conducted
      considering the above-mentioned benefits and complications including PJK or PJF
      in ASD. LEVEL OF EVIDENCE: 4.

PMID- 29215494
TI  - Descriptive Analysis of State and Federal Spine Surgery Malpractice Litigation in
      the United States.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: This study aimed to determine
      the factors associated with malpractice litigation in cases involving spine
      surgery in the United States. SUMMARY OF BACKGROUND DATA: Medical malpractice is
      of substantial interest to the medical community due to concerns of increased
      health care costs and medical decision-making for the sole purpose of reducing
      legal liability. METHODS: The Westlaw online legal database (Thomson Reuters, New
      York, NY) was searched for verdict and settlement reports pertaining to spine
      surgery from 2010 to 2015. Data were collected regarding type of procedure,
      patient age and gender, defendant specialty, outcome, award, alleged cause of
      malpractice, and factors involved in the plaintiff's decision to file. Initial
      search queried 187 cases, after which exclusion criteria were applied to
      eliminate duplicates and cases unrelated to spine surgery, yielding a total of 98
      cases for analysis. RESULTS: The verdict was in favor of the defendant in 62
      cases (63.3%). Neurosurgeons and orthopedic surgeons were the most common
      defendants in 29 (17.3%) and 40 (23.8%) of the cases, respectively. A perceived
      lack of informed consent was noted as a factor in 24 (24.4%) of the cases. A
      failure to diagnose or a failure to treat was noted in 31 (31.6%) and 32 (32.7%)
      cases, respectively. Median payments for plaintiff verdicts were nearly double
      those of settlements ($2,525,000 vs. $1,300,000). A greater incidence of
      plaintiff verdicts was noted in cases in which a failure to treat (P < 0.05) was
      cited, a patient death occurred (P < 0.05), or an emergent surgery had been
      performed (P < 0.01). CONCLUSION: Overall, physicians were not found liable in
      the majority of spine surgery malpractice cases queried. LEVEL OF EVIDENCE: 4.

PMID- 29215495
TI  - Caregiver Perceptions and Health-Related Quality-of-Life Changes in Cerebral
      Palsy Patients After Spinal Arthrodesis.
AB  - STUDY DESIGN: A retrospective analysis of a prospective registry. OBJECTIVE: Our
      objective was to prospectively assess caregivers' perceptions regarding changes
      in the health-related quality of life (HRQL) of patients with cerebral palsy (CP)
      after spinal arthrodesis. We assessed caregiver perceptions from three
      perspectives: 1) qualitative assessment of changes in global quality of life,
      comfort, and health; 2) relative valuation of spine surgery versus other common
      interventions in CP patients; and 3) quantitative changes in HRQL scores. SUMMARY
      OF BACKGROUND DATA: Studies of children with CP who undergo surgical treatment of
      spinal deformity have focused largely on radiographic changes. METHODS: We
      queried a multicenter prospective registry of CP patients with level IV or V
      motor function according to the Gross Motor Function Classification System who
      were treated with spinal arthrodesis, and whose caregivers completed preoperative
      and 2-year postoperative qualitative and quantitative HRQL surveys. A total of
      212 caregivers and their patients were included in the study. RESULTS: At 2-year
      follow-up, most caregivers reported that patients' global quality of life,
      comfort, and health were "a lot better" after spinal arthrodesis. Spinal
      arthrodesis was ranked as the most beneficial intervention in the patients' lives
      by 74% of caregivers, ahead of hip, knee, and foot surgeries and baclofen pump
      insertion. Gastrostomy tube insertion was the only intervention ranked superior
      to spinal arthrodesis in terms of impact. Quantitative HRQL scores improved
      significantly during 2-year follow-up across various domains. CONCLUSION: In
      qualitative and quantitative HRQL assessments, caregivers reported overall
      improvement in patients' lives after spinal arthrodesis. Caregivers ranked spine
      surgery as the most beneficial intervention in the patients' lives, secondary
      only to gastrostomy tube insertion. LEVEL OF EVIDENCE: 2.

PMID- 29215496
TI  - Comparing Health-Related Quality of Life Outcomes in Patients Undergoing Either
      Primary or Revision Anterior Cervical Discectomy and Fusion.
AB  - STUDY DESIGN: A retrospective review of prospectively collected data. OBJECTIVE:
      Compare health-related quality of life (HRQOL) outcome metrics in patients
      undergoing primary and revision anterior cervical discectomy and fusion (ACDF).
      SUMMARY OF BACKGROUND DATA: ACDF is associated with significant improvements in
      HRQOL outcome metrics. However, 2.9% of patients per year will develop
      symptomatic adjacent segment disease and there is a paucity of literature on
      HRQOL outcomes after revision ACDF. METHODS: Patients were identified who
      underwent either a primary or revision ACDF, and who had both preoperative and a
      minimum of 1-year postoperative HRQOL outcome data. Pre- and postoperative Short
      Form 12 Physical Component Score (SF12 PCS), Short Form 12 Mental Component Score
      (SF12 MCS) Visual Analog Scale for neck pain (VAS-Neck), VAS-Arm, and Neck
      Disability Index (NDI) scores were compared. RESULTS: A total of 360 patients
      (299 primary, 61 revision) were identified. Significant improvement in SF12 PCS,
      NDI, VAS-Neck, and VAS-Arm was seen in both groups; however, only a significant
      improvement in SF12 MCS was seen in the primary group. When comparing the results
      of a primary versus a revision surgery, the SF12 PCS score was the only outcome
      with a significantly different net improvement in the primary group (7.23 +/-
      9.72) compared to the revision group (2.9 +/- 11.07; P = 0.006) despite similar
      baseline SF12 PCS scores. The improvement in each of the other reported HRQOL
      outcomes did not significantly vary between surgical groups. CONCLUSION: A
      revision ACDF for cervical radiculopathy or myelopathy leads to a significant
      improvement in the HRQOL outcome, and with the exception of the SF12 PCS, these
      results are similar to those of patients undergoing a primary ACDF. LEVEL OF
      EVIDENCE: 2.

PMID- 29215497
TI  - Sex Differences for Anterior Cervical Fusion: Complications and Length of Stay.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To assess differences in baseline
      characteristics between sexes of patients undergoing anterior cervical discectomy
      and fusion (ACDF) and risk factors for adverse outcomes according to sex. SUMMARY
      OF BACKGROUND DATA: ACDF is a common treatment for cervical spine disease. To
      reduce the rate of complications, risk factors associated with adverse events
      have been identified. However, few studies have examined the risk for inferior
      outcomes or complications after ACDF by sex. METHODS: The American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was
      used to identify patients who underwent ACDF from 2005 through 2014. Data
      collected included demographics, comorbidities, operative characteristics, and
      postoperative adverse events. Demographic and comorbidity variables were compared
      between men and women using chi-squared analysis. Perioperative outcomes were
      compared between groups using multivariate linear regression or Poisson
      regression with robust error variance controlling for preoperative
      characteristics. RESULTS: In the 20,383 patients who met inclusion criteria, the
      male cohort was slightly older, less likely to be normal weight or morbidly
      obese, and had a higher incidence of diabetes and hypertension (P < 0.001 for
      each). Male sex was associated with a greater risk of any adverse event (relative
      risk = 1.2; P = 0.043), as well as any severe adverse event (relative risk  =
      1.4; P = 0.001). Moreover, male sex exhibited longer operative times compared to
      the female group (127 vs. 117 min; beta = 10; P < 0.001). CONCLUSION: The results
      of the current study suggest male sex is associated with an increased risk of
      adverse events following ACDF. Male sex has previously been demonstrated to
      correlate with medical comorbidities, which may be partly responsible for the
      increased morbidity. Because of the contrasting evidence throughout the
      literature, further studies are required to better elucidate this effect. LEVEL
      OF EVIDENCE: 3.

PMID- 29215498
TI  - Postoperative Deep Vein Thrombosis, Pulmonary Embolism, and Myocardial
      Infarction: Complications After Therapeutic Anticoagulation in the Patient With
      Spine Trauma.
AB  - STUDY DESIGN: A retrospective review (2001-2014) was conducted using
      prospectively collected data at a level I trauma center. OBJECTIVE: We sought to
      determine the incidence and characteristics of complications occurring secondary
      to therapeutic anticoagulation in adult spine trauma patients. SUMMARY OF
      BACKGROUND DATA: Numerous studies have assessed prophylactic anticoagulation
      after spine surgery, but none has investigated the risks of therapeutic doses of
      anticoagulation for treatment of postoperative thromboembolic events. METHODS:
      Patients were included if they sustained a postoperative thromboembolic event
      (deep venous thrombosis, pulmonary embolism, or myocardial infarction). Patients
      were excluded if anticoagulation was subtherapeutic. Of 1712 patients, 62 who
      received therapeutic anticoagulation and 174 propensity-matched control patients
      who did not receive therapeutic anticoagulation were included in the study.
      RESULTS: Initial anticoagulation was obtained by heparin infusion (51%), low
      molecular-weight heparin (LMWH, 46%), and warfarin (3%). Complications requiring
      unplanned reoperation occurred in 18% of anticoagulated patients and 10% of
      nonanticoagulated patients (P = 0.17). The reoperation rate after heparin
      infusion was 31% and after LMWH was 6.5% (P = 0.02). Epidural hematoma occurred
      in 3% and 1% of anticoagulated and nonanticoagulated patients, respectively.
      Multivariate logistic regression analysis of the two groups showed a trend toward
      increased risk of reoperation in the anticoagulation group. Analysis of the
      heparin infusion subgroup separate from the LMWH subgroup compared with the
      control group showed an increased risk of reoperation for any complication (odds
      ratio, 3.57; P = 0.01) and for bleeding complications (odds ratio, 43.1; P =
      0.01). CONCLUSION: This is the first study to quantify complications secondary to
      postoperative therapeutic anticoagulation in spine patients. Postoperative spine
      trauma patients who underwent therapeutic anticoagulation experienced an
      unplanned reoperation rate of 18%, including a 3% incidence of spinal epidural
      hematoma. Therapeutic anticoagulation using heparin infusion seems to drive the
      overall rate of reoperation (31%) compared with LMWH. LEVEL OF EVIDENCE: 3.

PMID- 29215499
TI  - Postoperative Emergency Department Utilization and Hospital Readmission After
      Cervical Spine Arthrodesis: Rates, Trends, Causes, and Risk Factors.
AB  - STUDY DESIGN: Retrospective state database analysis. OBJECTIVE: To quantify the
      30- and 90-day emergency department (ED) utilization and inpatient readmission
      rates after primary cervical arthrodesis, to stratify these findings by surgical
      approach, and to describe risk factors and conditions precipitating these events.
      SUMMARY OF BACKGROUND DATA: Limited data exist on ED utilization and hospital
      readmission rates after cervical spine arthrodesis. METHODS: The New York State
      all-payer health-care database was queried to identify all 87,045 patients who
      underwent primary subaxial cervical arthrodesis from 1997 through 2012.
      Demographic data and clinical information were extracted. Readmission data were
      available for the entire study period, whereas ED utilization data collection
      began later and was therefore analyzed starting in 2005. Incidences of these
      events within 30 and 90 days of discharge as well as trends over time were
      tabulated. The conditions prompting these encounters were also collected. Data
      were analyzed with respect to surgical approach. RESULTS: The hospital
      readmission rate was 4.2% at 30 days and 6.2% at 90 days postoperatively.
      Approximately 6.2% of patients were managed in the ED without inpatient admission
      within 30 days and 11.3% within 90 days of surgery. The most common conditions
      prompting such events were dysphagia or dysphonia, respiratory complications, and
      infection. ED utilization and readmission rates were lowest after anterior
      surgeries. A preoperative Charlson Comorbidity Index of 1 or greater and
      traumatic pathologies were associated with increased risk of subsequent ED
      utilization or hospital readmission. Thirty-day hospital readmission rates
      declined after 2010, whereas 30-day ED utilization continued to increase.
      CONCLUSION: Patient comorbidities, traumatic pathologies, and surgical approach
      are associated with increased postoperative complications. Anterior procedures
      carry the lowest risk, followed by posterior and then circumferential. Awareness
      of these findings should help to encourage development of strategies to minimize
      the rate of postoperative ED utilization and hospital readmission. LEVEL OF
      EVIDENCE: 3.

PMID- 29215500
TI  - Feasibility and Accuracy of Thoracolumbar Minimally Invasive Pedicle Screw
      Placement With Augmented Reality Navigation Technology.
AB  - STUDY DESIGN: Cadaveric laboratory study. OBJECTIVE: To assess the feasibility
      and accuracy of minimally invasive thoracolumbar pedicle screw placement using
      augmented reality (AR) surgical navigation. SUMMARY OF BACKGROUND DATA: Minimally
      invasive spine (MIS) surgery has increasingly become the method of choice for a
      wide variety of spine pathologies. Navigation technology based on AR has been
      shown to be feasible, accurate, and safe in open procedures. AR technology may
      also be used for MIS surgery. METHODS: The AR surgical navigation was installed
      in a hybrid operating room (OR). The hybrid OR includes a surgical table, a
      motorized flat detector C-arm with intraoperative 2D/3D imaging capabilities,
      integrated optical cameras for AR navigation, and patient motion tracking using
      optical markers on the skin. Navigation and screw placement was without any x-ray
      guidance. Two neurosurgeons placed 66 Jamshidi needles (two cadavers) and 18
      cannulated pedicle screws (one cadaver) in the thoracolumbar spine. Technical
      accuracy was evaluated by measuring the distance between the tip of the actual
      needle position and the corresponding planned path as well as the angles between
      the needle and the desired path. Time needed for navigation along the virtual
      planned path was measured. An independent reviewer assessed the postoperative
      scans for the pedicle screws' clinical accuracy. RESULTS: Navigation time per
      insertion was 90 +/- 53 seconds with an accuracy of 2.2 +/- 1.3 mm. Accuracy was
      not dependent on operator. There was no correlation between navigation time and
      accuracy. The mean error angle between the Jamshidi needles and planned paths was
      0.9 degrees  +/- 0.8 degrees . No screw was misplaced outside the pedicle. Two
      screws breached 2 to 4 mm yielding an overall accuracy of 89% (16/18).
      CONCLUSION: MIS screw placement directed by AR with intraoperative 3D imaging in
      a hybrid OR is accurate and efficient, without any fluoroscopy or x-ray imaging
      during the procedure. LEVEL OF EVIDENCE: N/A.

PMID- 29215501
TI  - Predictive Modeling for Blood Transfusion After Adult Spinal Deformity Surgery: A
      Tree-Based Machine Learning Approach.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Blood transfusion is
      frequently necessary after adult spinal deformity (ASD) surgery. We sought to
      develop predictive models for blood transfusion after ASD surgery, utilizing both
      classification tree and random forest machine-learning approaches. SUMMARY OF
      BACKGROUND DATA: Past models for transfusion risk among spine surgery patients
      are disadvantaged through use of single-institutional data, potentially limiting
      generalizability. METHODS: This investigation was conducted utilizing the
      American College of Surgeons National Surgical Quality Improvement Program
      dataset years 2012 to 2015. Patients undergoing surgery for ASD were identified
      using primary-listed current procedural terminology codes. In total, 1029
      patients were analyzed. The primary outcome measure was intra-/postoperative
      blood transfusion. Patients were divided into training (n = 824) and validation
      (n = 205) datasets. Single classification tree and random forest models were
      developed. Both models were tested on the validation dataset using area under the
      receiver operating characteristic curve (AUC), which was compared between models.
      RESULTS: Overall, 46.5% (n = 479) of patients received a transfusion
      intraoperatively or within 72 hours postoperatively. The final classification
      tree model used operative duration, hematocrit, and weight, exhibiting AUC = 0.79
      (95% confidence interval 0.73-0.85) on the validation set. The most influential
      variables in the random forest model were operative duration, surgical
      invasiveness, hematocrit, weight, and age. The random forest model exhibited AUC
      = 0.85 (95% confidence interval 0.80-0.90). The difference between the
      classification tree and random forest AUCs was nonsignificant at the validation
      cohort size of 205 patients (P = 0.1551). CONCLUSION: This investigation produced
      tree-based machine-learning models of blood transfusion risk after ASD surgery.
      The random forest model offered very good predictive capability as measured by
      AUC. Our single classification tree model offered superior ease of
      implementation, but a lower AUC as compared to the random forest approach,
      although this difference was not statistically significant at the size of our
      validation cohort. Clinicians may choose to implement either of these models to
      predict blood transfusion among their patients. Furthermore, policy makers may
      use these models on a population-based level to assess predicted transfusion
      rates after ASD surgery. LEVEL OF EVIDENCE: 3.

PMID- 29215502
TI  - Functional Limitations Due to Stiffness After Long-Level Spinal Instrumented
      Fusion Surgery to Correct Lumbar Degenerative Flat Back.
AB  - STUDY DESIGN: A retrospective analysis of functional limitations due to stiffness
      after long-level spinal instrumented fusion surgery to correct lumbar
      degenerative flat back was performed. OBJECTIVE: To analysis the functional
      limitations in patients treated surgically for adult lumbar degenerative flat
      back (ALDFB) with long-level instrumented fusion to the sacrum or pelvis. SUMMARY
      OF BACKGROUND DATA: Long-level instrumented fusion for ALDFB decreases back pain
      and spinal deformity. On the contrary, this surgery considerably eliminates
      spinal range of motion. This may have the potential to impair function and
      ability to perform activities of daily living (ADLs). METHODS: Consecutive 44
      patients who underwent long-level instrumented fusion to the sacrum or pelvis for
      ALDFB were retrospectively included in this study. All patients were followed up
      for a minimum of 13 months. The Lumbar Stiffness Disability Index for Korean
      Lifestyle and Oswestry Disability Index were administered and analyzed to assess
      the impact of spinal stiffness on daily living. Cohorts were defined based on the
      upper instrumented vertebrae (above T10 [group 1] or below L1 [group 2]) and
      lower instrumented vertebrae (S1 pedicle screw [group S] or iliac bolt screw
      [group I]). RESULTS: All patients showed deteriorated postoperative ADLs compared
      to preoperative values. Group 1 showed deterioration postoperatively compared to
      group 2. Group 1 showed deteriorated postoperative ADLs compared to preoperative
      values. In group 2, question 5 and 7 showed deterioration postoperatively
      compared to preoperative values, and question 2 and 10 showed improvement
      postoperatively compared to preoperative values. Group I showed deterioration
      postoperatively compared to group S. CONCLUSION: This study will hopefully allow
      surgeons to provide patients with ALDFB with a more informed explanation of
      expected surgery effects on specific ADLs. LEVEL OF EVIDENCE: 3.

PMID- 29215503
TI  - Minimum Detectable Measurement Difference for Health-Related Quality of Life
      Measures Varies With Age and Disability in Adult Spinal Deformity: Implications
      for Calculating Minimal Clinically Important Difference.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To investigate the minimum
      detectable measurement difference (MDMD) in the Scoliosis Research Society-22r
      (SRS-22r) outcomes instrument in adult spinal deformity (ASD) and to evaluate the
      effect of baseline data on measurable difference. SUMMARY OF BACKGROUND DATA: The
      minimum clinically important difference (MCID) is the smallest, clinically
      relevant change observed and has been proposed for the SRS-22r instrument in ASD
      as 0.4. The MCID must be greater than the MDMD to be useful. The MDMD for the SRS
      22r has not been calculated, nor have the effect of patient baseline values on
      MDMD. METHODS: A prospective observation cohort was queried for patients treated
      both operatively and nonoperatively for ASD. Patients with baseline and 1-year, 2
      year follow-up SRS-22r data were included in the analysis. The MDMD was
      calculated using classical test theory and item-response theory methods. Effect
      size and standardized response means were calculated. The effect of baseline data
      values was evaluated for MDMD. RESULTS: A total 839 Patients were eligible for
      cohort inclusion with 428 (51%) eligible for analysis with complete data. MDMD
      for Pain (0.6) and Self-Image (0.5) were greater than 0.4. MDMD varied with age
      (highest for the youngest patients) and with disability (highest for SF-36
      Physical Component Summary <28.6). MDMD was less than 0.4 for Activity (0.3),
      Mental Health (0.3), and Total Score (0.2). Gender and mental health did not
      affect MDMD for the SRS-22r instrument. CONCLUSION: An MCID of 0.4 for the SRS
      22r total score and domain scores may not be an appropriate value as the
      calculated MDMD is greater than 0.4 for both the Pain and Self-Image subscores.
      The MDMD for the SRS-22r instrument varied with age and baseline disability,
      making the assessment of clinically significant change more difficult using this
      tool. The MCID must be considered in the setting of the MDMD for instruments used
      to assess outcomes in ASD. LEVEL OF EVIDENCE: 3.

PMID- 29215504
TI  - Is Health-related Quality of Life Decreased in Adolescents With Back Pain?
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the association
      between back pain and health-related quality of life (HRQoL) among adolescents.
      SUMMARY OF BACKGROUND DATA: The prevalence of back pain has been increasing not
      only in the adult population but also among children and adolescents. The better
      knowledge about the association between back pain and health-related quality of
      life could facilitate the implementation of new intervention strategies on
      prevention and treatment of back pain. METHODS: A sample of 350 students from the
      fifth to ninth grades of one public school in Niteroi, Rio de Janeiro, Brazil.
      Anthropometric measures and information regarding sociodemographic, lifestyle,
      frequency and intensity of neck (NP), thoracic (TP), and low back pain in the
      previous month were collected using a personal digital assistant. HRQoL was
      assessed by KIDSCREEN-27. Multiple linear regression analyses were performed to
      investigate the association between back pain and HRQoL by sex. RESULTS: The mean
      age of participants was 12.7 (+/-1.6) years. Frequency of NP, TP, and low back
      pain was 34.3, 27.1, and 13.1%, respectively. The mean intensity of pain was 2.3
      (+/-0.2) for neck, 2.0 (+/-0.2) for thoracic, and 1.3 (+/-0.1) for low back pain.
      The presence of two/three painful sites was reported by 21.7% of the adolescents.
      The frequency and severity of neck pain were inversely associated with global
      HRQoL in both the sexes. There is a strong inverse association between the number
      of painful sites and global HRQoL and domains. CONCLUSION: The presence and
      intensity of cervical pain and the number of painful regions were associated with
      lower HRQoL in adolescents, which is worrying due to the important relationship
      between back pain in the adolescence and in the adulthood. LEVEL OF EVIDENCE: 3.

PMID- 29215505
TI  - Dynamic Fluctuation of Truncal Shift Parameters During Quiet Standing in Healthy
      Young Individuals.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To describe the dynamic
      fluctuation of truncal shift parameters during quiet standing in healthy young
      individuals using biomechanical analyses. SUMMARY OF BACKGROUND DATA: Coronal
      decompensation (CD) and sagittal vertical axis (SVA) are the key radiographic
      parameters to assess static truncal stability, with the known cut-off value of 4
      cm for SVA in determining severity of spinal deformity. These values are obtained
      at a specific moment during quiet standing, when the posture innately changes.
      Thus, unassessed truncal sway could potentially compromise the reliability of
      these measurements. METHODS: Previously obtained biomechanical data with 11 male,
      healthy participants aged 16 to 29 were used to quantify the dynamic sway of
      standing posture. The participants were instructed to quietly stand with surface
      reflective markers for 130 seconds. The midpoint of bilateral acromia was used as
      a surrogate for C7 vertebral body. The time series of coronal and sagittal shifts
      of C7 to sacrum were measured as quasi-coronal decompensation (CD) and quasi
      sagittal vertical axis (SVA) to simulate CD and SVA on radiographs. A force
      platform was also used to measure the center of pressure (COP) displacement.
      RESULTS: The group averages of the dynamic sway range were 20.2 +/- 4.1 mm
      (range: 15.1-28.6) in the sagittal plane (quasi-SVA) and 9.8 +/- 3.2 mm (range:
      5.5-15.2) in the coronal plane (quasi-CD). There were significant correlations
      between quasi-CD sway and medial-lateral COP velocity (Pearson r = 0.65, P =
      0.03), as well as between quasi-SVA sway and COP sway area (r = 0.65, P = 0.03).
      CONCLUSION: Given the considerable fluctuation of quasi-SVA and quasi-CD during
      quiet standing, the reliability of radiographic measurement using CD and SVA at a
      specific moment can be substantially compromised. The assessment based on the
      currently proposed cut-off values should be interpreted with caution, and repeat
      examinations are warranted. LEVEL OF EVIDENCE: 4.

PMID- 29215506
TI  - Can Early Patient-reported Outcomes Be Used to Identify Patients at Risk for Poor
      1-Year Health Outcomes After Lumbar Laminectomy With Arthrodesis?
AB  - STUDY DESIGN: Prospective cohort. OBJECTIVE: Determine A) between-patient
      variability in patient-reported outcomes (PROs) at four postoperative time
      points; B) within-patient correlation of 1-year PROs with PROs at three earlier
      time points; and C) ability of early PROs to predict 1-year PROs after lumbar
      laminectomy with arthrodesis. SUMMARY OF BACKGROUND DATA: It is unclear whether
      early PROs can help identify patients at risk for poor health outcomes. METHODS:
      Between 2015 and 2016, we assessed pre- and postoperative back pain, leg pain,
      disability, physical health, and mental health in 146 patients. We examined PRO
      variability between patients and correlations within patients during the first
      postoperative year. For early (<=3-mo) and 1-year PROs, we examined concordance
      between experiencing a minimal important difference (MID) early and at 1 year and
      odds of experiencing a 1-year MID given early absence of a MID. RESULTS:
      Postoperatively, we found increasing between-patient variability of PROs. For
      individual patients, we found moderate to strong between-assessment correlations
      (intraclass correlations) between repeated PROs (back pain, 0.47; leg pain, 0.51;
      disability, 0.47; physical health, 0.63; mental health, 0.53). Early MIDs were
      experienced for back pain (57%), leg pain (52%), physical health (38%),
      disability (34%), and mental health (16%). Concordance was moderate for leg pain
      (0.48), mental health (0.46), disability (0.38), back pain (0.36), and physical
      health (0.25). In patients without an early MID, odds of experiencing a MID at 1
      year were low for physical health (odds ratio [OR] = 0.33), back pain (OR =
      0.30), leg pain (OR = 0.14), and disability (OR = 0.11) but not mental health (OR
      = 0.50). CONCLUSION: Although postoperative recovery is variable, early PROs can
      identify patients at risk for poor 1-year outcomes and may help tailor care
      during the first year after lumbar laminectomy with arthrodesis. LEVEL OF
      EVIDENCE: 2.

PMID- 29215508
TI  - Opioid Knowledge and Prescribing Practices Among Obstetrician-Gynecologists.
AB  - OBJECTIVE: To describe obstetrician-gynecologists' (ob-gyns) knowledge and
      prescribing practices regarding opioid analgesics. METHODS: We conducted a cross
      sectional survey of a national sample of American College of Obstetricians and
      Gynecologists Fellows and Junior Fellows who are part of the Collaborative
      Ambulatory Research Network. We used a sequential mixed-method approach. We
      collected data on opioid knowledge and typical prescribing practices, including
      number, type, and indication for prescriptions. We determined adherence to four
      recommended practices: 1) screening for dependence, 2) prescribing the smallest
      amount required, 3) tailoring prescriptions, and 4) counseling on proper
      disposal. We also explored variables associated with prescribing practices.
      RESULTS: Sixty percent (179/300) of sampled members responded. Respondents
      reported prescribing a median of 26 (5-80) pills per patient across all
      indications combined. Ninety-eight percent prescribed opioids after surgery and a
      smaller proportion for nonsurgical indications: vaginal birth (22%), ovarian
      cysts (30%), endometriosis (24%), and chronic pelvic pain of unknown cause (18%).
      The number prescribed varied only by indication for the prescription. Nineteen
      percent reported adherence to three or more (of four) recommended practices.
      There was no significant difference in the median number of pills prescribed
      between those who reported adherence to at least one compared with those who did
      not adhere to any recommended practices (25 [interquartile range 25-30] vs 28
      [interquartile range 20-30], P=.58). Regarding knowledge, 81% incorrectly
      identified the main source of misused opioids, which is through diversion from a
      friend or family member, and 44% did not know how to properly dispose of unused
      prescription opioids. CONCLUSION: Obstetrician-gynecologists reported prescribing
      a median of 26 opioid pills across all indications combined. Amount prescribed
      varied widely by indication but not by reported adherence to recommended
      prescribing practices. This study highlights an urgent need for increased efforts
      to improve ob-gyns' knowledge of opioid use, misuse, disposal, and best
      prescribing practices.

PMID- 29215507
TI  - Robotic Gastrotomy With Intracorporeal Suture for Patients With Gastric
      Gastrointestinal Stromal Tumors Located at Cardia and Subcardiac Region.
AB  - PURPOSE: Few studies of robotic gastric gastrointestinal stromal tumors (GISTs)
      resection have been conducted. This study was aimed to evaluate the robotic
      gastrotomy with intracorporeal suture for patients with GISTs located at cardia
      and subcardiac region. MATERIALS AND METHODS: From January 2014 to August 2016,
      11 patients with GISTs located at cardia and subcardiac region underwent robotic
      gastrotomy with intracorporeal suture. Data of these patients were collected.
      RESULTS: The mean operative time was 82.7 minutes and the mean blood loss was
      30.0 mL. No complication was reported. The postoperative length of stay was 3.3
      days. On postoperative day 14, inflammation recovered to preoperative level. On
      postoperative month 6, the nutritional status was similar to that before the
      surgery. After 25.5 months follow-up, all patients survived with no recurrence or
      metastasis. CONCLUSIONS: Robotic gastrotomy with intracorporeal suture for
      patients with GISTs located at cardia and subcardiac region is safe and feasible.

PMID- 29215509
TI  - Interval Female Sterilization.
AB  - Female sterilization is relied on by nearly one in three women aged 35-44 years
      in the United States. Sterilization procedures are among the most common
      procedures that obstetrician-gynecologists perform. The most frequent
      sterilization procedures include postpartum tubal ligation, laparoscopic tubal
      disruption or salpingectomy, and hysteroscopic tubal occlusion. The informed
      consent process for sterilization is crucial and requires shared decision-making
      between the patient and the health care provider. Counseling should include the
      specific risks and benefits of the specific surgical approaches. Additionally,
      women should be counseled on the alternatives to sterilization, including
      intrauterine contraceptives and subdermal contraceptive implants. Complications,
      including unplanned pregnancy after successful female sterilization, are rare.
      The objectives of this Clinical Expert Series are to describe the epidemiology of
      female sterilization, access to postpartum sterilization, advances in interval
      sterilization techniques, and clinical considerations in caring for women
      requesting sterilization.

PMID- 29215510
TI  - Timing and Risk Factors of Postpartum Stroke.
AB  - OBJECTIVE: To characterize risk and timing of postpartum stroke readmission after
      delivery hospitalization discharge. METHODS: The Healthcare Cost and Utilization
      Project's Nationwide Readmissions Database for calendar years 2013 and 2014 was
      used to perform a retrospective cohort study evaluating risk of readmission for
      stroke within 60 days of discharge from a delivery hospitalization. Risk was
      characterized as odds ratios (ORs) with 95% CIs based on whether patients had
      hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), or
      chronic hypertension, or neither disorder during the index hospitalization.
      Adjusted models for stroke readmission risk were created. RESULTS: From January
      1, 2013, to October 31, 2013, and January 1, 2014, to October 31, 2014, 6,272,136
      delivery hospitalizations were included in the analysis. One thousand five
      hundred five cases of readmission for postpartum stroke were identified. Two
      hundred fourteen (14.2%) cases of stroke occurred among patients with
      hypertensive diseases of pregnancy, 66 (4.4%) with chronic hypertension, and
      1,225 (81.4%) without hypertension. The majority of stroke readmissions occurred
      within 10 days of hospital discharge (58.4%), including 53.2% of patients with
      hypertensive diseases of pregnancy during the index hospitalization, 66.7% with
      chronic hypertension, and 58.9% with no hypertension. Hypertensive diseases of
      pregnancy and chronic hypertension were associated with increased risk of stroke
      readmission compared with no hypertension (OR 1.74, 95% CI 1.33-2.27 and OR 1.88,
      95% CI 1.19-2.96, respectively). Median times to readmission were 8.9 days for
      hypertensive diseases of pregnancy, 7.8 days for chronic hypertension, and 8.3
      days without either condition. CONCLUSION: Although patients with chronic
      hypertension and hypertensive diseases of pregnancy are at higher risk of
      postpartum stroke, they account for a minority of such strokes. The majority of
      readmissions for postpartum stroke occur within 10 days of discharge; optimal
      blood pressure management may be particularly important during this period.

PMID- 29215511
TI  - Liposomal Bupivacaine During Robotic Colpopexy and Posterior Repair: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To evaluate the effect of liposomal bupivacaine on postoperative pain
      among patients undergoing robotic sacrocolpopexy with posterior repair. METHODS:
      This was a randomized, patient-blinded, placebo-controlled trial of women
      undergoing robotic sacrocolpopexy with posterior repair. Liposomal bupivacaine or
      normal saline placebo was injected into laparoscopic and vaginal incisions at
      completion of surgery. Perioperative care was standardized. Visual analog scales
      were collected at 4, 18, and 24 hours postoperatively in hospital. Starting on
      postoperative day 1, participants completed twice-daily pain scales and a pain
      medication diary up until the evening of postoperative day 3. The primary outcome
      was a 20-mm change in the visual analog scale 18 hours postoperatively. Secondary
      measures included additional pain scores, satisfaction, and narcotic use. Sample
      size calculation revealed that 32 patients per arm were required to detect the 20
      mm difference with 90% power and an alpha of 0.05. To allocate for dropout, a
      goal of 70 was set. RESULTS: Between March 2015 and April 2016, 100 women were
      screened and 70 women were enrolled: 35 women were randomized to liposomal
      bupivacaine and 35 to placebo, of whom 64 (91%) were included in the final
      analysis: 33 liposomal bupivacaine and 31 placebo. No difference in demographics,
      surgical data, or satisfaction between groups was noted. Median VAS at 18 hours
      after surgery was not statistically different in those who received liposomal
      bupivacaine compared with normal saline (15 mm compared with 20 mm; P=.52). Other
      pain scales and total morphine equivalents were also similar (P=.90). CONCLUSION:
      In this study of robotic sacrocolpopexy with posterior repair, there were no
      differences in pain scores or narcotic use between liposomal bupivacaine and
      placebo injected into laparoscopic and vaginal incisions. Given its lack of
      clinical benefit, routine use of liposomal bupivacaine is not supported for this
      surgical intervention. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02449915.

PMID- 29215512
TI  - Term Elective Induction of Labor and Pregnancy Outcomes Among Obese Women and
      Their Offspring.
AB  - OBJECTIVE: To evaluate whether elective induction of labor between 39 through 41
      weeks of gestation, as compared with expectant management, is associated with
      reduced cesarean delivery and other adverse outcomes among obese women and their
      offspring. METHODS: We conducted a retrospective cohort study using the 2007-2011
      California Linked Patient Discharge Data-Birth Cohort File of 165,975 singleton,
      cephalic, nonanomalous deliveries to obese women. For each gestational week (39
      41), we used multivariable logistic regression models, stratified by parity, to
      assess whether elective induction of labor or expectant management was associated
      with lower odds of cesarean delivery and other adverse outcomes. RESULTS: At 39
      and 40 weeks of gestation, cesarean delivery was less common in obese nulliparous
      women who were electively induced compared with those who were expectantly
      managed (at 39 weeks of gestation, frequencies were 35.9% vs 41.0%, respectively
      [P<.05]; adjusted odds ratio [OR] 0.82, 95% CI 0.77-0.88). Severe maternal
      morbidity was less frequent among electively induced obese nulliparous patients
      (at 39 weeks of gestation, 5.6% vs 7.6% [P<.05]; adjusted OR 0.75, 95% CI 0.65
      0.87). Neonatal intensive care unit admission was less common among electively
      induced obese nulliparous women (at 39 weeks of gestation, 7.9% vs 10.1% [P<.05];
      adjusted OR 0.79, 95% CI 0.70-0.89). Patterns were similar among obese parous
      women at 39 weeks of gestation (crude frequencies and adjusted ORs [95% CIs] were
      as follows: for cesarean delivery, 7.0% vs 8.7% [P<.05] and 0.79 [0.73-0.86]; for
      severe maternal morbidity, 3.3% vs 4.0% [P<.05] and 0.83 [0.74-0.94]; for
      neonatal intensive care unit admission: 5.3% vs 7.4% [P<.05] and 0.75 [0.68
      0.82]). Similarly, elective induction at 40 weeks of gestation was associated
      with reduced odds of cesarean delivery, maternal morbidity, and neonatal
      intensive care unit admission among both obese nulliparous and parous patients.
      CONCLUSION: Elective labor induction after 39 weeks of gestation was associated
      with reduced maternal and neonatal morbidity among obese women. Further
      prospective investigation is necessary.

PMID- 29215513
TI  - Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With
      the Levonorgestrel-Releasing Intrauterine Device.
AB  - OBJECTIVE: To assess efficacy of the levonorgestrel-releasing intrauterine device
      (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial
      cancer. METHODS: This retrospective case series included all patients treated
      with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial
      cancer from January 2003 to June 2013. Response rates were calculated and the
      association of response with clinicopathologic factors, including age, body mass
      index, and uterine size, was determined. RESULTS: Forty-six patients diagnosed
      with complex atypical hyperplasia or early-grade endometrial cancer were treated
      with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had
      complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and
      eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI
      57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95%
      CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2
      endometrial cancer. Of the clinicopathologic features evaluated, there was a
      trend toward the association of lack of exogenous progesterone effect in the
      pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter
      was 1.3 cm larger in women who did not respond to the IUD (P=.04). CONCLUSION:
      Levonorgestrel-releasing IUD therapy for the conservative treatment of complex
      atypical hyperplasia or early-grade endometrial cancer resulted in return to
      normal histology in a majority of patients.

PMID- 29215514
TI  - Misoprostol With Foley Bulb Compared With Misoprostol Alone for Cervical
      Ripening: A Randomized Controlled Trial.
AB  - OBJECTIVE: To test the hypothesis that cervical ripening using a combination of
      misoprostol and a transcervical Foley bulb leads to delivery within a shorter
      time compared with misoprostol alone. METHODS: This randomized controlled trial
      was offered to women admitted for cervical ripening. Inclusion criteria were
      gestational age 37 weeks or greater with intact membranes, singleton fetus,
      cephalic presentation, and Bishop score 6 or less. Exclusion criteria included,
      among others, prior uterine surgery, ruptured membranes, and any contraindication
      to vaginal delivery. Patients were randomized to cervical ripening using
      misoprostol and a transcervical Foley bulb simultaneously or misoprostol alone.
      Primary outcome was time from placement of the misoprostol to delivery. Secondary
      outcomes included time to active phase, time from active phase to delivery,
      cesarean delivery rate, uterine tachysystole, estimated blood loss,
      chorioamnionitis, cord pH, 5-minute Apgar score, and neonatal intensive care unit
      admission. Sample size calculation revealed that 94 participants were required in
      each group to detect a 3-hour difference with 80% power and alpha error of 0.05.
      Intention-to-treat analysis was performed. RESULTS: From September 2015 to July
      2016, a total of 200 patients were randomized, 100 to each group. There were no
      differences between groups with respect to parity, body mass index, gestational
      age, Bishop score, birth weight, or indication for induction. Time to delivery
      was significantly shorter in the combined misoprostol-transcervical Foley group:
      15.0 (11.0-21.8) hours (median [interquartile range]) vs 19.0 (14.0-27.3) hours
      in the misoprostol-only group (P=.001). This time difference remained significant
      after subanalysis by parity or after excluding cesarean deliveries. There was no
      difference between groups with respect to the rate or indication for cesarean
      delivery, estimated blood loss, rate of tachysystole, chorioamnionitis, or
      neonatal outcomes. CONCLUSION: Cervical ripening using misoprostol in combination
      with a transcervical Foley bulb is an effective method to shorten the course of
      labor compared with misoprostol alone. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02566005.

PMID- 29215515
TI  - Isolated Absent Thelarche in a Patient With Neurofibromatosis Type 1 and
      Acromegaly.
AB  - BACKGROUND: Isolated absent thelarche is a rare condition that is infrequently
      reviewed in the literature. CASE: A 28-year-old woman with neurofibromatosis type
      1 and acromegaly presented with absent breast development despite hormone
      therapy. Examination noted a normally developed woman with acromegalic features
      and Tanner stage I breasts. Hormone studies and karyotype were normal. Magnetic
      resonance imaging of the patient's brain demonstrated a voluminous pituitary.
      Chromosome microarray analysis diagnosed the neurofibromatosis 1 microdeletion
      syndrome. Breast ultrasonography and surgical consultation were offered.
      CONCLUSIONS: Neither neurofibromatosis type 1, acromegaly, nor neurofibromatosis
      1 microdeletion syndrome are linked to absent thelarche. After attempting hormone
      therapy, patients with absent thelarche should be evaluated for congenital breast
      anomalies, estrogen receptor abnormalities, or gene defects. Psychological and
      surgical consultation should also be offered.

PMID- 29215516
TI  - Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.
AB  - OBJECTIVE: To compare time to ovulation, ovulation rates, and side effect profile
      of traditional and the stair-step protocol for ovulation induction using
      clomiphene citrate in women with polycystic ovary syndrome (PCOS). METHODS: We
      performed a retrospective study of women seeking care for infertility with a
      diagnosis of PCOS at a university-based infertility clinic from July 2012 to July
      2014. We included patients who were resistant to the initial starting dose of 50
      mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes
      included ovulation rates, clinical pregnancy rates, and mild and moderate-to
      severe side effects based on dose. For the traditional protocol, higher doses of
      clomiphene were used each subsequent month if no ovulation occurred. For the
      stair-step protocol, higher doses of clomiphene were given 7 days after the last
      dose if no dominant follicles were seen on ultrasonography. Our study had 80%
      power to detect a 20% difference in ovulation. RESULTS: One hundred nine patients
      were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%)
      in the stair-step protocol. Age and body mass index were similar between groups.
      The time to ovulation was decreased in the stair-step protocol group compared
      with the traditional protocol group (23.1+/-0.9 days vs 47.5+/-6.3 days).
      Ovulation rates were increased in the stair-step group compared with the
      traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%]
      vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was
      achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an
      increased incidence of mild side effects (vasomotor flushes, headaches,
      gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]),
      but there was no difference in the incidence of severe side effects (headaches,
      visual disturbances). CONCLUSION: For women with PCOS, the stair-step clomiphene
      protocol is associated with decreased time to ovulation and increased ovulation
      rates at higher doses when compared with the traditional protocol.

PMID- 29215517
TI  - Two-Year Results of Burch Compared With Midurethral Sling With Sacrocolpopexy: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate 1- and 2-year urinary continence rates after Burch
      retropubic urethropexy compared with a retropubic midurethral sling for women
      with urinary incontinence undergoing sacrocolpopexy. METHODS: We conducted a
      planned secondary analysis of a multicenter, randomized, single-blind trial
      comparing Burch with a sling that enrolled participants from June 2009 to August
      2013. Objective outcome measures of continence were assessed at 1- and 2-year
      follow-up through office visits and validated questionnaires. Overall continence
      was defined as a negative stress test, no retreatment for stress incontinence,
      and no self-reported urinary incontinence (International Consultation on
      Incontinence Questionnaire, Short Form, score, 0). Stress-specific continence was
      defined as fulfillment of the first two criteria and no self-reported stress
      related incontinence. Primary outcomes were assessed with intention-to-treat and
      within-protocol analyses. Comparisons between groups were evaluated using chi or
      Fisher exact test. RESULTS: The two groups were similar in all measured baseline
      features. Outcome assessments at 2 years were available for 48 of 57 patients
      (84%) in the sling group and 45 of 56 patients (80%) in the Burch group. With
      intention-to-treat analysis, the sling group had significantly higher rates of
      overall continence than the Burch group (49% [28/57] vs 29% [16/56]; 95% CI for
      absolute risk difference 3.0-38.1; P=.03) at 1- but not 2-year follow-up (47%
      [27/57] vs 32% [18/56]; 95% CI for absolute risk difference -2.6 to 33.1; P=.10).
      The sling group had significantly higher rates of stress-specific continence than
      the Burch group at 1-year (70% [40/57] vs 46% [26/56]; 95% CI for absolute risk
      difference 6.1-41.4; P=.01) and 2-year (70% [40/57] vs 45% [25/56]; 95% CI for
      absolute risk difference 7.9-43.2; P=.006) follow-up. No difference was detected
      in prolapse recurrence, voiding dysfunction, antimuscarinic medication use,
      urgency incontinence, or patient satisfaction. CONCLUSION: Among women with
      baseline urinary incontinence undergoing sacrocolpopexy, the retropubic
      midurethral sling resulted in higher stress-specific continence rates than Burch
      retropubic urethropexy at 1- and 2-year follow-up.

PMID- 29215518
TI  - Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe
      Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis.
AB  - OBJECTIVE: To evaluate whether daily low-molecular-weight (LMW) heparin
      prophylaxis during pregnancy alters profile of circulating angiogenic factors
      that have been linked with the pathogenesis of preeclampsia and fetal growth
      restriction. METHODS: This is a planned ancillary study of the Heparin
      Preeclampsia trial, a randomized trial in pregnant women with a history of severe
      early-onset preeclampsia (less than 34 weeks of gestation). In the parent study,
      all women were treated with aspirin and then randomized to receive LMW heparin or
      aspirin alone. In this study, we measured serum levels of circulating angiogenic
      factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble
      endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks,
      14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7
      weeks, and 34-37 6/7 weeks. RESULTS: Samples were available from 185 patients:
      LMW heparin+aspirin (n=92) and aspirin alone (n=93). The two groups had
      comparable baseline characteristics and had similar adverse composite outcomes
      (35/92 [38.0%] compared with 36/93 [38.7%]; P=.92). There were no significant
      differences in serum levels of soluble fms-like tyrosine kinase-1, placental
      growth factor, and soluble endoglin in the participants who received LMW heparin
      and aspirin compared with those who received aspirin alone regardless of
      gestational age period. Finally, women who developed an adverse composite outcome
      at less than 34 weeks of gestation demonstrated significant alterations in serum
      angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks
      preceding delivery. CONCLUSION: Prophylactic LMW heparin therapy when beginning
      from before 14 weeks of gestation with aspirin during pregnancy is not associated
      with an improved angiogenic profile. This may provide a molecular explanation for
      the lack of clinical benefit noted in recent trials. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00986765.

PMID- 29215519
TI  - Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture:
      A Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate the use of a transcervical Foley catheter plus oxytocin
      infusion compared with oxytocin infusion alone for labor induction and cervical
      ripening in women 34 weeks of gestation or greater with prelabor rupture of
      membranes. METHODS: This is a randomized, multicenter trial of women with a live,
      singleton gestation at 34 weeks of gestation or greater with prelabor rupture of
      membranes, an unfavorable cervical examination (less than 2 cm or 80% effaced),
      and no contraindication to labor. Participants were randomly allocated to a
      transcervical Foley catheter inflated to 30 cc with concurrent oxytocin infusion
      or oxytocin infusion alone. Oxytocin administration was standardized across
      sites. The primary study outcome was interval from induction to delivery. To
      detect a 2.5-hour difference in the interval from induction to delivery, we
      required outcome data on 194 women, assuming 80% power and a two-tailed alpha of
      5%. Analysis was by intent to treat. RESULTS: We enrolled 201 women: 93 were
      allocated to Foley and 108 to oxytocin. Demographics were similar between the
      groups. Time to delivery was not significantly different between groups: in the
      Foley group, it was 13.9 hours (+/-6.9 SD) compared with 14.4 hours (+/-7.9 SD)
      in the oxytocin group (P=.69). There were more cases of clinical chorioamnionitis
      (8% compared with 0%, P<.01) in the Foley group compared with the oxytocin group.
      There were no differences for other infectious morbidities or any other variable
      studied. CONCLUSION: In patients with prelabor rupture of membranes, the use of a
      transcervical Foley catheter in addition to oxytocin does not shorten the time to
      delivery compared with oxytocin alone, but may increase the incidence of
      intraamniotic infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01973036.

PMID- 29215520
TI  - Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney
      Transplantation.
AB  - OBJECTIVE: Preeclampsia often complicates pregnancies after maternal kidney
      transplantation. We aimed to assess whether preeclampsia is associated with
      kidney function decline either during the pregnancy or in the long term. METHODS:
      We performed an international multicenter retrospective cohort study. Renal
      function at conception, pregnancy outcomes, and short- and long-term graft
      outcomes were collected for women who were pregnant after renal transplantation
      and had transplant and obstetric care at the participating centers. In women who
      had multiple pregnancies during the study period, only the last pregnancy was
      included. Univariate and multivariable analyses were performed. RESULTS: We
      retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic
      hypertension was present at baseline in 27%. Mean estimated glomerular filtration
      rate (GFR) at start of pregnancy was 52.4+/-17.5 mL/min/1.73 m. Mean estimated
      GFR at delivery was 47.6+/-21.6 mL/min/1.73 m, which was significantly lower than
      at conception (P=.03). Twenty women (38%) developed preeclampsia. In
      multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m
      higher drop in estimated GFR between conception and delivery than women who did
      not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained
      at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last
      follow-up was 38+/-23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss
      over the follow-up period. Incidence of graft loss was similar in women with and
      without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99).
      In multivariable analysis, the decrease in estimated GFR between conception and
      last follow-up was similar in women who experienced preeclampsia during pregnancy
      and those who did not (difference -2.69 mL/min/1.73 m, P=.65). CONCLUSION:
      Preeclampsia commonly complicates pregnancies after renal transplantation but is
      not associated with long-term renal dysfunction or graft loss.

PMID- 29215521
TI  - Pregnancy After Uterine Rupture.
AB  - A 28-year-old woman, gravida 3 para 2, with two previous cesarean deliveries
      presents for prenatal care. Her second pregnancy was complicated by a uterine
      rupture at 36 weeks of gestation. She asks, "When should I be delivered during
      the current pregnancy?"

PMID- 29215522
TI  - Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage.
AB  - OBJECTIVE: To compare the rates of invasive procedures (surgical or vascular) for
      hemorrhage control between a perinatal network that routinely used intrauterine
      balloon tamponade and another perinatal network that did not in postpartum
      hemorrhage management. METHODS: This population-based retrospective cohort study
      included all women (72,529) delivering between 2011 and 2012 in the 19 maternity
      units in two French perinatal networks: a pilot (in which balloon tamponade was
      used) and a control network. Outcomes were assessed based on discharge abstract
      data from the national French medical information system. General and obstetric
      characteristics were included in two separate multivariate logistic models
      according to the mode of delivery (vaginal and cesarean) to estimate the
      independent association of the network with invasive procedures. RESULTS:
      Invasive procedures (pelvic vessel ligation, arterial embolization, hysterectomy)
      were used in 298 women and in 4.1 per 1,000 deliveries (95% CI 3.7-4.6). The
      proportion of women with at least one invasive procedure was significantly lower
      in the pilot network (3.0/1,000 vs 5.1/1,000, P<.01). Among women who delivered
      vaginally, the use of arterial embolization was also significantly lower in the
      pilot than the control network (0.2/1,000 vs 3.7/1,000, P<.01) as it was for
      those who delivered by cesarean (1.3/1,000 vs 5.7/1,000, P<.01). After
      controlling for potential confounding factors, the risk of an invasive procedure
      among women who delivered vaginally remained significantly lower in the pilot
      network (adjusted odds ratio [OR] 0.14, 95% CI 0.08-0.27), but not for women who
      delivered by cesarean (adjusted OR 1.19, 95% CI 0.87-1.61). CONCLUSION: The use
      of intrauterine balloon tamponade in routine clinical practice was associated
      with a significantly lower use of invasive procedures for hemorrhage control
      among women undergoing vaginal delivery.

PMID- 29215523
TI  - Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral
      Renal Agenesis.
AB  - Congenital bilateral renal agenesis has been considered a uniformly fatal
      condition. However, the report of using serial amnioinfusions followed by the
      live birth in 2012 and ongoing survival of a child with bilateral renal agenesis
      has generated hope, but also considerable controversy over an array of complex
      clinical and ethical concerns. To assess the ethical concerns associated with
      using serial amnioinfusions for bilateral renal agenesis, we assembled a
      multidisciplinary group to map the ethical issues relevant to this novel
      intervention. The key ethical issues identified were related to 1) potential
      risks and benefits, 2) clinical care compared with innovation compared with
      research, 3) counseling of expectant parents, 4) consent, 5) outcome measures, 6)
      access and justice, 7) conflicts of interest, 8) effects on clinicians, 9)
      effects on institutions, and 10) long-term societal implications. These ethical
      issues should be addressed in conjunction with systematic efforts to examine
      whether this intervention is safe and effective. Future work should capture the
      experiences of expectant parents, women who undergo serial amnioinfusions, those
      born with bilateral renal agenesis and their families as well as clinicians
      confronted with making difficult choices related to it.

PMID- 29215524
TI  - Urinary Tract Injury in Gynecologic Laparoscopy for Benign Indication: A
      Systematic Review.
AB  - OBJECTIVE: To perform a comprehensive literature review of the incidence,
      location, etiology, timing, management, and long-term sequelae of urinary tract
      injury in gynecologic laparoscopy for benign indication. DATA SOURCES: A
      systematic review of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was
      conducted. METHODS OF STUDY SELECTION: Four hundred thirty-three studies were
      screened for inclusion with 136 full-text articles reviewed. Ninety studies
      published between 1975 and 2015 met inclusion criteria, representing 140,444
      surgeries. Articles reporting the incidence of urinary tract injury in
      gynecologic laparoscopy for benign indication were included. Exclusion criteria
      comprised malignancy, surgery by urogynecologists, research not in English, and
      insufficient data. TABULATION, INTEGRATION, AND RESULTS: A total of 458 lower
      urinary tract injuries were reported with an incidence of 0.33% (95% CI 0.30
      0.36). Bladder injury (0.24%, 95% CI 0.22-0.27) was overall three times more
      frequent than ureteral injury (0.08%, 95% CI 0.07-0.10). Laparoscopic
      hysterectomy not otherwise specified (1.8%, 95% CI 1.2-2.6) and laparoscopically
      assisted vaginal hysterectomy (1.0%, 95% CI 0.9-1.2) had the highest rates of
      injury. Most ureteral injuries resulted from electrosurgery (33.3%, 95% CI 24.3
      45.8), whereas most bladder injuries resulted from lysis of adhesions (23.3%, 95%
      CI 18.7-29.0). Ureteral injuries were most often recognized postoperatively (60%,
      95% CI 47-76) and were repaired by open ureteral anastomosis (47.4%, 95% CI 36.3
      61.9). In contrast, bladder injuries were most often recognized intraoperatively
      (85%, 95% CI 75-95) and were repaired by laparoscopic suturing (34.9%, 95% CI
      29.2-41.7). CONCLUSION: The incidence of lower urinary tract injury in
      gynecologic laparoscopy for benign indication remains low at 0.33%. Bladder
      injury was three times more common than ureteral injury, although ureteral
      injuries were more often unrecognized intraoperatively and underwent open
      surgical repair. These risk estimates can assist gynecologic surgeons in
      effectively counseling their patients preoperatively concerning the risks of
      lower urinary tract injury.

PMID- 29215525
TI  - Low-Fidelity Simulator for the Standardized Training of Fetoscopic
      Meningomyelocele Repair.
AB  - BACKGROUND: Fetoscopic meningomyelocele repair in a gas-filled uterus is a new
      technique performed in very few centers. There are few opportunities as well as
      ethical prohibitions on the initial development and subsequent refinement of
      innovative fetal surgery techniques in humans, and using an animal model is both
      very expensive and logistically difficult. METHOD: We developed a low-fidelity
      endoscopic fetal surgery simulation using a plastic doll and pieces of chicken
      breast to simulate a fetal meningomyelocele, and a polyurethane ball to simulate
      a gas-filled uterus, along with a standard endoscopy system and instruments.
      EXPERIENCE: A unique two-port technique with significant differences from the
      standard laparoscopic surgery procedure was developed and refined through an
      iterative phase into a standardized methodology, and the simulator was then used
      to train three other teams to perform standardized fetoscopic meningomyelocele
      repair. CONCLUSION: A low-fidelity fetoscopic surgery simulator is a useful tool
      for developing new fetoscopic operations and for training multidisciplinary fetal
      surgery teams without the need for extensive use of an animal model. This
      simulator may be used to further explore the human uterus as a new surgical space
      for additional fetal surgeries.

PMID- 29215526
TI  - Challenges and Opportunities in Identifying, Reviewing, and Preventing Maternal
      Deaths.
AB  - Despite many efforts at the state, city, and national levels over the past 70
      years, a nationwide consensus on how best to identify, review, and prevent
      maternal deaths remains challenging. We present a brief history of maternal death
      surveillance in the United States and compare the three systems of national
      surveillance that exist today: the National Vital Statistics System, the
      Pregnancy Mortality Surveillance System, and maternal mortality review
      committees. We discuss strategies to address the perennial challenges of shared
      terminology and accurate, comparable data among maternal mortality review
      committees. Finally, we propose that with the opportunity presented by a
      systematized shared data system that can accurately account for all maternal
      deaths, state and local-level maternal mortality review committees could become
      the gold standard for understanding the true burden of maternal mortality at the
      national level.

PMID- 29215527
TI  - Long-term Trends in Singleton Preterm Birth in South Australia From 1986 to 2014.
AB  - OBJECTIVE: To describe long-term trends in the prevalence of preterm birth and
      rates of preterm birth in singleton pregnancies complicated by hypertensive
      disorders of pregnancy, small for gestational age (SGA), and preterm prelabor
      rupture of membranes (PROM) in South Australia. METHODS: We conducted a
      retrospective population study including all singleton live births in the state
      of South Australia from 1986 to 2014. Long-term trends for preterm birth,
      hypertensive disorders of pregnancy, SGA, preterm PROM as well as stillbirth were
      assessed using joinpoint regression analyses. Trends in maternal age, body mass
      index (BMI), ethnic diversity, parity, and smoking over time were also assessed.
      RESULTS: From 1986 to 2014, with a total of 539,234 singleton births, the overall
      preterm birth rates increased from 5.1% to 7.1% (P<.001) and for iatrogenic
      preterm birth increased from 1.6% to 3.2% (P<.001). The incidence of hypertensive
      disorders of pregnancy decreased from 8.7% to 7.2%. Among pregnancies complicated
      by hypertensive disorders of pregnancy, the proportion of preterm birth increased
      (10.4-17.5%, P<.001). The incidence of SGA decreased from 11.1% to 8.0%. Among
      pregnancies complicated by SGA, the proportion of preterm birth increased (2.9
      5.4%, P<.001). The incidence of preterm PROM increased from 1.4% to 2.2%. Among
      pregnancies complicated by preterm PROM, the proportion of preterm birth remained
      stable. Preterm stillbirth rates declined (4.23-2.32%, P<.001). Maternal age,
      BMI, and ethnic diversity have all increased since 1986, whereas maternal smoking
      has decreased. CONCLUSION: In South Australia, the preterm birth rate among
      singletons increased from 1986 to 2014 by 40%, with iatrogenic preterm birth
      being responsible for 80% of this increase. Incidence of hypertensive disorders
      of pregnancy and SGA declined. Among pregnancies complicated by hypertensive
      disorders of pregnancy and SGA, the proportions of preterm birth increased,
      indicating earlier interventions in these women. The diagnosis of preterm PROM
      increased from 1% to 2%, and greater than 80% of preterm PROM was associated with
      preterm birth after 1990. Increasing iatrogenic delivery may be attributable, in
      part, to changing maternal phenotype and to altered clinicians' behavior.
      However, improvements in fetal surveillance, particularly ultrasonography, and
      advanced neonatal care may underpin perinatal clinical decision-making and the
      likelihood of iatrogenic birth.

PMID- 29215528
TI  - What Is New in Global Women's Health? (Part 1): Best Articles From the Past Year.
AB  - This month we focus on current research in global women's health. Drs. Ramsey and
      Stuart discuss four recent publications, which are concluded with a "bottom line"
      that is a take-home message. A complete reference for each can be found in on
      this page along with direct links to abstracts.

PMID- 29215529
TI  - Connect the Dots-January 2018.

PMID- 29215530
TI  - Happy 65th Anniversary to Obstetrics & Gynecology.

PMID- 29215532
TI  - IMAGING OF VITELLIFORM MACULAR LESIONS USING POLARIZATION-SENSITIVE OPTICAL
      COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To examine the involvement of the retinal pigment epithelium (RPE) in
      the presence of vitelliform macular lesions (VML) in Best vitelliform macular
      dystrophy (BVMD), autosomal recessive bestrophinopathy, and adult-onset
      vitelliform macular degeneration using polarization-sensitive optical coherence
      tomography (PS-OCT). METHODS: A total of 35 eyes of 18 patients were imaged using
      a PS-OCT system and blue light fundus autofluorescence imaging. Pathogenic
      mutations in the BEST1 gene, 3 of which were new, were detected in all patients
      with BVMD and autosomal recessive bestrophinopathy. RESULTS: Polarization
      sensitive optical coherence tomography showed a characteristic pattern in all
      three diseases with nondepolarizing material in the subretinal space consistent
      with the yellowish VML seen on funduscopy with a visible RPE line below it. A
      focal RPE thickening was seen in 26 eyes under or at the edge of the VML. Retinal
      pigment epithelium thickness outside the VML was normal or mildly thinned in
      patients with BVMD and adult-onset vitelliform macular degeneration but was
      diffusely thinned or atrophic in patients with autosomal recessive
      bestrophinopathy. Patients with autosomal recessive bestrophinopathy showed sub
      RPE fibrosis alongside the subretinal VML. Polarization-sensitive optical
      coherence tomography was more reliable in assessing the localization and the
      integrity of the RPE than spectral domain OCT alone. On spectral domain OCT,
      identification of the RPE was not possible in 19.4% of eyes. Polarization
      sensitive optical coherence tomography allowed for definite identification of the
      location of VML in respect to the RPE in all eyes, since it provides a tissue
      specific contrast. CONCLUSION: Polarization-sensitive optical coherence
      tomography confirms in vivo the subretinal location of VML and is useful in the
      assessment of RPE integrity.

PMID- 29215531
TI  - Human Immunodeficiency Virus (HIV)- and Non-HIV-Associated Immunosuppression and
      Risk of Cervical Neoplasia.
AB  - OBJECTIVE: To estimate the risk of cervical intraepithelial neoplasia grade 2, 2
      3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human
      immunodeficiency virus (HIV)- and non-HIV-associated immunosuppression. METHODS:
      We performed a case-control study of 20,146 women with incident CIN 2 or worse
      and 5:1 age-matched, incidence-density selected women in a control group
      (n=100,144) enrolled in an integrated health care system from 1996 to 2014.
      Adjusted rate ratios (RRs) from conditional logistic regression were obtained for
      HIV status (stratified by CD4 T-cells), solid organ transplant history, and
      immunosuppressive medication use. RESULTS: Risk of CIN 2 or worse was increased
      among women with HIV (n=36 women in the case group and 79 women in the control
      group; adjusted RR 2.0, 95% CI 1.3-3.0) compared with those without HIV and in
      solid organ transplant recipients (n=51 women in the case group and 68 women in
      the control group; RR 3.3, 95% CI 2.3-4.8) compared with women without a prior
      transplant. The highest risks were among women with HIV and less than 200 CD4 T
      cells/microliter (n=9 women in the case group and eight women in the control
      group; RR 5.6, 95% CI 2.1-14.7) compared with those without HIV and in solid
      organ transplant recipients prescribed three or greater immunosuppressive
      medication classes (n=32 women in the case group and 33 women in the control
      group; RR 4.1, 95% CI 2.5-6.8) compared with women without a prior transplant and
      zero medication classes. No increased risks were observed for women with HIV and
      500 or greater CD4 T-cells/microliter (n=9 women in the case group and 43 women
      in the control group; RR 0.8, 95% CI 0.4-1.7) compared with those without HIV or
      women without prior solid organ transplantation prescribed two or fewer
      immunosuppressive medication classes (n=1,262 women in the case group and 6,100
      women in the control group; RR 0.95, 95% CI 0.89-1.01) compared with women
      without and a prior transplant and zero medication classes. CONCLUSION: Risk of
      CIN 2 or worse is increased in women with a prior solid organ transplant or who
      have HIV and CD4 cells/microliter less than 500 but not in women with HIV and
      higher CD4 levels or in women without a prior solid organ transplant but who are
      prescribed only one or two immunosuppressive medication classes.

PMID- 29215533
TI  - SURGICAL REMOVAL OF EPIRETINAL MEMBRANE WITH AND WITHOUT REMOVAL OF INTERNAL
      LIMITING MEMBRANE: Comparative Study of Visual Acuity, Features of Optical
      Coherence Tomography, and Recurrence Rate.
AB  - PURPOSE: To study and compare visual acuity, foveal thickness, outer limiting
      layer, ellipsoid zone, and recurrence rate in patients undergoing removal of the
      epiretinal membrane with and without the removal of the internal limiting
      membrane (ILM). METHODS: Sixty-three patients who had the epiretinal membrane
      removed by a single surgeon were randomly assigned into 2 groups: Group 1 without
      additional removal of the ILM and Group 2 with removal of the ILM. Patients were
      followed up and evaluated at the first month, third month, and sixth month,
      postoperatively. RESULTS: Patients from both groups had a gradual improvement in
      their vision over time. There was no significant difference in the improvement in
      visual acuity between the two groups. About tomographic assessment of
      alterations, no significant differences were found between the groups; however,
      Group 1 had a higher relapse rate (17%) compared with Group 2 (3.6%) (P = 0.09).
      CONCLUSION: Epiretinal membrane removal with and without ILM peeling shows
      similar functional and anatomical improvements, but the group in which the ILM
      was not removed seemed to have a higher recurrence rate.

PMID- 29215534
TI  - Incidence and Predictors of Readmissions in Acute Pancreatitis: A Nationwide
      Analysis.
AB  - OBJECTIVES: Acute pancreatitis (AP) is a common cause for hospitalization, and
      readmission is common, with variable associated risk factors for readmission.
      Here, we assessed the incidence and risk factors for readmission in AP in a large
      national database. METHODS: We analyzed data from the National Readmission
      Database during the year 2013. Index admissions with a primary discharge
      diagnosis of AP using the International Classification of Diseases, Ninth
      Revision, Clinical Modification were identified from January to November to
      identify 30-day readmission rates. Demographic, hospital, and clinical diagnoses
      were included in multivariate regression analysis to identify readmission risk
      factors. RESULTS: We identified 243,816 index AP discharges with 39,623 (16.2%)
      readmitted within 30 days. The most common reason for readmission was recurrent
      AP (41.5%). Increased odds of all-cause readmission were associated with younger
      age, nonhome discharge, increasing Charlson Comorbidity Index, and increased
      length of stay. Cholecystectomy during index admission was associated with
      reduced all-cause and recurrent AP readmissions (odds ratios of 0.5, and 0.35,
      respectively). CONCLUSIONS: Readmission for AP is common, most often due to
      recurrent AP. Multiple factors, including cholecystectomy, during index
      admission, are associated with significantly reduced odds of all-cause and
      recurrent AP readmissions.

PMID- 29215535
TI  - The Clinicopathological Aspects of Primary Presacral Neuroendocrine Neoplasms:
      One Center Experience.
AB  - OBJECTIVES: Presacral neuroendocrine neoplasms (NENs) are rare entities that are
      found at the presacral space. We report our experience in the diagnosis,
      management, and outcomes of primary presacral NENs. METHODS: This was an
      institutional review board-approved retrospective review of medical records and
      surgical pathology specimens of patients with a diagnosis of NENs at Cedars-Sinai
      Medical Center between January 2000 and April 2016. RESULTS: Ten patients were
      identified. The median age at presentation was 38 years (range, 20-77 years), and
      8 were women. One patient presented with carcinoid-like symptoms, 2 were
      diagnosed incidentally, and 7 presented with symptoms related to mass effect. The
      median size of the tumor was 7.0 cm (range, 3-12 cm). On pathologic review, 3 of
      10 were low-grade and well-differentiated, 5 of 10 were intermediate-grade and
      well-differentiated, 2 of 10 were grade 3 and classified as high-grade and poorly
      differentiated neuroendocrine tumors. Seven cases were metastatic on presentation
      with lymph node, liver, lung, or skeletal metastasis. Seven of 8 cases were
      detectable using Octreoscan. Eight patients were treated with a somatostatin
      analog and 5 patients were treated surgically. CONCLUSIONS: Presacral NENs are
      clinically similar to gastroenteropancreatic tumors. Octreoscan imaging and
      somatostatin analog therapies were frequently applied. Further biologic
      characterization of this rare subtype is needed.

PMID- 29215537
TI  - Simultaneous Pancreas and Kidney Transplantation is Associated With Inferior Long
      Term Outcomes in African Americans.
AB  - OBJECTIVES: Simultaneous pancreas and kidney transplant (SPK) is the most
      effective treatment for patients with type 1 diabetes mellitus and renal failure.
      However, the effect of ethnicity on SPK outcomes is not well understood. METHODS:
      We studied the influence of recipient ethnicity on SPK using the United Network
      for Organ Sharing database. A retrospective review of 20,196 SPK patients from
      1989 to 2014 was performed. The recipients were divided into 4 groups: 15,833
      whites (78.40%), 2708 African Americans (AA) (14.39%), 1456 Hispanics (7.21%),
      and 199 Asians (0.99%). RESULTS: Hispanics and Asians experienced the best
      overall graft and patient outcomes. Both groups demonstrated significantly
      superior graft and patient survival rates compared with whites at 1, 3, 5, 10,
      and 15 years (all P < 0.0001). African Americans experienced significantly
      superior 1- and 3-year patient survival compared with whites (both P < 0.0001).
      African Americans also experienced significantly superior 1-year kidney and
      pancreas graft survival compared with whites (P < 0.0001). However, AA
      experienced significantly inferior patient and allograft outcomes for all other
      time points compared with whites. CONCLUSIONS: Based on United Network for Organ
      Sharing data from 1989 to 2014, AA have worse long-term patient and graft
      survival rates compared with whites, Hispanics, and Asians undergoing SPK.

PMID- 29215536
TI  - Comparison of Various Scoring Systems and Biochemical Markers in Predicting the
      Outcome in Acute Pancreatitis.
AB  - OBJECTIVE: Early risk assessment is important in acute pancreatitis (AP). The
      primary objective of this study was to compare various scores and biochemical
      markers done on the day of admission in predicting the outcome. METHODS:
      Demographic, clinical, and laboratory data of patients presenting within 2 weeks
      of onset were collected. Various scores were calculated and biochemical markers
      were measured on the day of admission. Optimum cutoffs were identified through
      receiver operating curve analysis. Multivariate analysis was used to identify
      predictors of outcome. RESULTS: Of 343 patients included, 202 (59%) were male;
      mean (SD) age was 38.7 (15.5) years. Acute pancreatitis was severe in 170 (49.6%)
      patients. Twenty-eight percent of the patients developed infected pancreatic
      necrosis and 18% died. An Acute Physiology and Chronic Health Evaluation (APACHE
      II) score of at least 7, bedside index for severity of AP (BISAP) of at least 2,
      systemic inflammatory response syndrome score of at least 3, and C-reactive
      protein of at least 82 ng/mL predicted severity. Predictors of infected
      pancreatic necrosis were as follows: PANC 3 score of at least 1, BISAP score of
      at least 2, and Marshall score of at least 2, whereas C-reactive protein of
      greater than 98, BISAP score of at least 2, APACHE score of at least 10, and a
      blood urea nitrogen of at least 17 predicted mortality. CONCLUSIONS: Both BISAP
      and APACHE II are comparable in predicting outcome, but BISAP predicted all 3
      outcomes with the same cutoff and hence is a robust scoring system.

PMID- 29215538
TI  - Cortisol Outperforms Novel Cardiovascular, Inflammatory, and Neurohumoral
      Biomarkers in the Prediction of Outcome in Acute Pancreatitis.
AB  - OBJECTIVES: The aims of this study were to assess whether copeptin, pro-atrial
      natriuretic peptide, proadrenomedullin, and cortisol are associated with disease
      severity in patients with acute pancreatitis (AP) and to compare their ability in
      predicting organ failure or death. METHODS: From April 2011 to January 2015, 142
      patients with AP were included in this prospective single-center study and
      observed for 4 days. Disease severity was rated by the Atlanta 1992 and 2012
      criteria and organ failure by the modified Marshall score. The aforementioned
      laboratory markers, C-reactive protein, and procalcitonin were measured. RESULTS:
      Patients with moderate to severe AP showed significantly higher plasma
      concentrations of all biomarkers than did those with mild AP. Overall, 30 organ
      failures or deaths occurred. All biomarkers except cortisol had only modest
      discriminatory ability, with areas under the receiver operating characteristic
      curve (AUCs) between 0.44 and 0.66. Cortisol showed an AUC of 0.78 compared with
      the Acute Physiology and Chronic Health Evaluation II score with an AUC of 0.75.
      CONCLUSIONS: Cortisol was the best predictor of organ failure or death. All
      biomarkers were associated with disease severity to a similar degree as C
      reactive protein, the criterion-standard marker in AP. Further studies are
      warranted to define their clinical role.

PMID- 29215539
TI  - Biliary Stenting in Patients With Pancreatic Cancer: Results From a Population
      Based Cohort Study.
AB  - OBJECTIVE: We aimed to describe management of biliary obstruction (BO) in the
      context of pancreatic cancer within a population-based cohort. METHODS: We
      examined management of BO in 1863 patients diagnosed as having pancreatic cancer
      in 2010/2011. We used descriptive statistics and logistic regression to describe
      patterns of biliary stent usage, complications and duration of patency,
      associations between preoperative stenting and surgical outcomes, and between
      patient factors and management of jaundice. RESULTS: Almost half of the people in
      the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of
      these had at least 1 stent inserted. Preoperative stenting, mostly with plastic
      stents, occurred for 72% of patients who experienced jaundice prior to an
      attempted resection but was not associated with surgical outcomes. Seventy
      percent of the jaundiced patients who did not have an attempted resection were
      stented. Metal stents were less frequently replaced within 30 days than plastic
      (9% vs 42%). Living in a rural area was associated with reduced likelihood of
      having jaundice managed. CONCLUSIONS: Plastic stents were still used frequently,
      despite guidelines recommending metal in most contexts. Patients living in rural
      areas were less likely to have BO managed. This work highlights the need to
      monitor current practice.

PMID- 29215540
TI  - The Insulin Receptor Is Colocalized With the TRPV1 Nociceptive Ion Channel and
      Neuropeptides in Pancreatic Spinal and Vagal Primary Sensory Neurons.
AB  - OBJECTIVES: Recent observations demonstrated the expression of the insulin
      receptor (InsR) and its functional interaction with the transient receptor
      potential vanilloid type 1 receptor (TRPV1) in sensory ganglion neurons. Because
      sensory nerves are implicated in pancreatic inflammatory processes, we studied
      the colocalization of the InsR with TRPV1 and proinflammatory neuropeptides in
      spinal and vagal pancreatic afferent neurons. METHODS: Immunohistochemistry and
      quantitative morphometry were used to analyze the expression of TRPV1, InsR,
      substance P (SP), and calcitonin gene-related peptide (CGRP) in retrogradely
      labeled pancreatic dorsal root ganglion (DRG) and nodose ganglion (NG) neurons.
      RESULTS: The proportions of retrogradely labeled pancreatic TRPV1-, InsR-, SP-,
      and CGRP-immunoreactive neurons amounted to 68%, 48%, 33%, and 54% in DRGs and
      64%, 49%, 40%, and 25% in the NGs. Of the labeled DRG and NG neurons, 23% and 35%
      showed both TRPV1 and InsR immunoreactivity. Colocalization of the InsR with SP
      or CGRP was demonstrated in 14% and 28% of pancreatic DRG and 24% and 8% of
      pancreatic NG neurons. CONCLUSIONS: The present findings provide morphological
      basis for possible functional interactions among the nociceptive ion channel
      TRPV1, the InsR, and the proinflammatory neuropeptides SP and CGRP expressed by
      pancreatic DRG and NG neurons.

PMID- 29215541
TI  - Pancreatic Insufficiency in Cystic Fibrosis: Influence of Inflammatory Response
      Genes.
AB  - OBJECTIVE: Pancreatic insufficiency (PI) in cystic fibrosis (CF) patients is a
      crucial clinical marker for severity and disease progression. In our study, 125
      modifier genes and their SNPs were associated between CF patients with PI or
      pancreatic sufficiency. METHODS: We prospectively evaluated 214 CF patients
      admitted at 1 hospital for a 2-year period. The PI status was associated with
      clinical variables and SNPs related with inflammatory response considering CFTR
      mutations. Open Array technique was used to perform the SNPs identification.
      RESULTS: For PI risk, after correction by multiple test, in CF patients and 2
      CFTR mutations class I, II, and/or III, there were 6 SNPs with positive
      association (P < 0.005). The odds ratio amplitude was 0.087 (95% confidence
      interval [CI], 0.004-0.544) for rs9870255*CG (CTNNB1 gene) to 11.06 (95% CI,
      1.746-252.3) for rs729302*AA (IRF5 gene). For all CF patients at the same time, 9
      SNPs showed positive association. The odds ratio amplitude was 0.144 (95% CI,
      0.028-0.602) for rs2348071*AA (PSMA3 gene) to 5.809 (95% CI, 1.536-37.54) for
      rs11702779*AA (RUNX1 gene). In our data, we observed the interaction between CFTR
      mutations, rs9870255*CTNNB1, rs9378805*IRF4, and rs7664617*KCNIP4 to PI status.
      CONCLUSIONS: Multiple SNPs in inflammatory response genes showed association with
      PI considering the CFTR mutations screening.

PMID- 29215542
TI  - Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology Combined With
      Automated Quantitative DNA Cytometry Can Improve the Value in the Detection of
      Pancreatic Malignancy.
AB  - OBJECTIVES: Quantitative DNA-image cytometry (ICM) is used to diagnose malignancy
      via detecting changes in DNA content. We aimed to estimate the value of cytology,
      DNA-ICM, and their combination in diagnosing pancreatic malignancy. METHODS: One
      hundred twenty-one endoscopic ultrasound-guided fine-needle aspiration samples
      from 116 patients suspected for pancreatic malignancy were examined by cytology
      and DNA-ICM. Their results and the final diagnoses (malignancy or not) were
      collected. Diagnostic values were compared among cytology, DNA-ICM, and their
      combination. RESULTS: The DNA-ICM had a lower sensitivity and accuracy than
      cytology (64.2% vs 81.1%; 71.9% vs 85.1%). The combination of the techniques
      significantly improved the diagnostic accuracy compared with that of cytology or
      DNA-ICM alone (0.932 vs 0.905, P = 0.02; 0.932 vs 0.821, P < 0.0001). Using the
      Youden index, we determined that one cell with DI (DNA index) >=2.5 is the
      optimal cutoff value for DNA-ICM to diagnose pancreatic malignancy. After
      adoption of this criterion, the sensitivity and accuracy were improved to 74.7%
      and 80.2% with DNA-ICM and 90.5% and 92.6% with the combined method. CONCLUSIONS:
      The DNA-ICM is an effective complementary method to cytology in diagnosing
      pancreatic malignancy. Although the diagnostic value for DNA-ICM is lower than
      that of cytology, an improved value was obtained after their combination.

PMID- 29215543
TI  - Fungal Infections in Patients With Infected Pancreatic Necrosis and Pseudocysts:
      Risk Factors and Outcome.
AB  - OBJECTIVES: Fungal infections in patients with acute pancreatitis are common and
      potentially life threatening. Data on fungal pancreatic infections are
      inconsistent. Therefore, the aim of this study was to identify risk factors for
      fungal infection and to determine their impact on survival. METHODS: This was a
      retrospective analysis of pathogen spectrum and outcome of infected pancreatic
      necrosis or pseudocysts from 3 German hospitals from 2002 to 2016. RESULTS: A
      total of 187 fine-needle aspirations were performed in 113 patients. Fungal
      pancreatic infections, predominantly caused by Candida species, were identified
      in 52 patients (46%). Antibiotic treatment before fine-needle aspiration (84.6%
      vs 49.2%, P = 0.003) and the duration of therapy (9 vs 2 days, P = 0.024)
      identified patients at an increased risk of fungal infection. Patients with
      fungal pancreatic infections had a longer hospital stay (34 vs 14 days, P <
      0.001), received intensive care treatment more often (55.8% vs 27.9%, P = 0.002),
      and had a lower 365-day survival (78.4 [SE, 6.6%] vs 95.0 [SE, 2.0%], P = 0.035)
      than patients with bacterial pancreatic infections only. CONCLUSIONS: Fungal
      infections are common in patients with infected pancreatic necrosis and
      pseudocysts and indicate patients with a higher risk of mortality in the long
      term.

PMID- 29215544
TI  - The -251 A/T Polymorphism in the IL8 Promoter is a Risk Factor for Acute
      Pancreatitis.
AB  - OBJECTIVES: Inflammation in the setting of acute pancreatitis (AP) is partially
      driven by pathogen recognition receptors that recognize damage-associated
      molecular patterns. Interleukin (IL)-8 is a chemotactic factor produced by
      pathogen recognition receptor-expressing cells. A single-nucleotide polymorphism
      in IL8 promoter region (-251 A/T) has been implicated in inflammatory diseases.
      We examined whether this IL8 polymorphism confers susceptibility to AP. METHODS:
      Patients with AP (n = 357) were prospectively recruited. Clinical data and blood
      were collected in subjects and controls (n = 347). Severity was defined following
      the Revised Atlanta Classification. Genotypes were assessed by quantitative
      polymerase chain reaction using TaqMan probes. RESULTS: Patients and controls had
      similar demographics and had no difference in Hardy-Weinberg (patients, P = 0.29;
      controls, P = 0.66). Twenty-five percent of patients developed severe AP.
      Compared with controls, the A/A genotype was more common in AP (P = 0.041; odds
      ratio, 1.42; 95% confidence interval, 1-1.99). Obese patients with the A/A
      genotype were more likely to develop mild AP (P = 0.047). CONCLUSIONS: The -251
      polymorphism confers susceptibility to AP and disease severity in obese patients.
      However, its effect is moderate. One potential mechanism for this susceptibility
      is via increased IL8 production by innate cells, with subsequent enhanced
      neutrophil influx and pancreatic injury.

PMID- 29215545
TI  - Metal Artifact-Free and Dose-Efficient Computed Tomography Imaging of a Cardiac
      Prosthetic Valve Using Spectral Shaping of the X-ray Beam: A Case Report.
AB  - Bioprosthetic valve (BPV) thrombosis can be challenging to diagnose with cardiac
      computed tomography owing to metal artifacts of the BPV. In this case report, an
      optimized metal artifact reduction protocol using a third-generation dual-source
      multidetector computed tomographic scanner with high kVp (Sn150kVp) and tin (Sn)
      filtration and high temporal resolution yielded high-quality, artifact-free,
      dynamic images of a thrombosed mitral BPV.

PMID- 29215546
TI  - Initial tadalafil and ambrisentan combination therapy in pulmonary arterial
      hypertension: cLinical and haemodYnamic long-term efficacy (ITALY study).
AB  - AIMS: Initial combination therapy with ambrisentan and tadalafil (upfront
      therapy) offers clinical benefits in pulmonary arterial hypertension (PAH) and
      reduces the risk of clinical failure compared with monotherapy in naive patients.
      The aim of study is to assess the efficacy of a 12-month upfront therapy with
      ambrisentan and tadalafil in improving haemodynamics in incident PAH patients.
      METHODS: This is a multicentre retrospective analysis of real-world Italian
      clinical data in 56 patients with newly diagnosed PAH. Clinical evaluations,
      including demographics, medical history, WHO functional class, 6-min walk
      distance, and right heart catheterization, were collected from the patients'
      medical records at baseline and at 12-month follow-up. RESULTS: At baseline,
      there were 16, 34, and 6 patients in WHO functional class II, III, and IV,
      respectively. Over a median follow-up of 12 months, 54 (96%) patients were still
      alive, 6 (11%) of whom received parenteral prostanoids. Ambrisentan-tadalafil
      combination was associated with significant improvements in WHO functional class
      (2.2 +/- 0.8 vs. 2.8 +/- 0.6, P < 0.001, improved in 29 patients), exercise
      capacity (395 +/- 123 vs. 353 +/- 101 m, P = 0.039), N-terminal probrain
      natriuretic peptide (528 +/- 493 vs. 829 +/- 620 pg/ml; P = 0.009), and
      haemodynamics (right atrial pressure 7 +/- 4 vs. 9 +/- 5 mmHg, P = 0.02; mean
      pulmonary artery pressure 45 +/- 15 vs. 50 +/- 13 mmHg, P = 0.03; cardiac index
      3.0 +/- 1.0 vs. 2.5 +/- 0.9 l/min/m, P = 0.001; pulmonary vascular resistance 8
      +/- 4 vs. 11 +/- 6 Wood units, P = 0.001) compared with baseline. CONCLUSIONS:
      Initial combination therapy with ambrisentan and tadalafil offers clinical
      benefits and significant haemodynamic improvement in newly diagnosed PAH
      patients.

PMID- 29215547
TI  - Hypnosis as an effective and inexpensive option to control pain in transcatheter
      ablation of cardiac arrhythmias.
AB  - : Supportive care for pain relief and back discomfort during electrophysiology
      interventions is usually needed in the electrophysiology lab, especially in long
      lasting procedures like atrial fibrillation ablation. Although this is usually
      achieved with conventional pharmacologic anesthesia, hypnosis has recently
      aroused interest as a reliable tool to complement and possibly enhance conscious
      sedation. We collected five case of percutaneous arrhythmia ablation in which,
      after informed consent, hypnosis was performed by nurse anesthetists in the cath
      lab. In each case at the end of the intervention, the patients described complete
      alterations of perception or memory of the pain or of the length of the study. No
      anesthetic drug was needed. While waiting for more robust data, we suggest
      hypnosis could be a reliable, inexpensive and well tolerated tool to obtain
      complete pain control and comfort during arrhythmia ablation.

PMID- 29215548
TI  - Secondary Metabolic Profiles of Two Cultivars of Piper nigrum (Black Pepper)
      Resulting from Infection by Fusarium solani f. sp. piperis.
AB  - Bragantina and Cingapura are the main black pepper (Piper nigrum L.) cultivars
      and the Para state is the largest producer in Brazil with about 90% of national
      production, representing the third largest production in the world. The infection
      of Fusarium solani f. sp. piperis, the causal agent of Fusarium disease in black
      pepper, was monitored on the cultivars Bragantina (susceptible) and Cingapura
      (tolerant), during 45 days' post infection (dpi). Gas Chromatography-Mass
      spectrometry (GC-MS) analysis of the volatile concentrates of both cultivars
      showed that the Bragantina responded with the production of higher contents of
      alpha-bisabolol at 21 dpi and a decrease of elemol, mostly at 30 dpi; while
      Cingapura displayed an decrease of delta-elemene production, except at 15 dpi.
      The phenolic content determined by the Folin Ciocalteu method showed an increase
      in the leaves of plants inoculated at 7 dpi (Bragantina) and 7-15 dpi
      (Cingapura); in the roots, the infection caused a phenolic content decrease in
      Bragantina cultivar at 45 dpi and an increase in the Cingapura cultivar at 15, 30
      and 45 dpi. High Performance Liquid Chromatography-Mass spectrometry (HPLC-MS)
      analysis of the root extracts showed a qualitative variation of alkamides during
      infection. The results indicated that there is a possible relationship between
      secondary metabolites and tolerance against phytopathogens.

PMID- 29215549
TI  - Nature Cure and Non-Communicable Diseases: Ecological Therapy as Health Care in
      India.
AB  - With rapidly increasing rates of non-communicable diseases, India is experiencing
      a dramatic public health crisis that is closely linked to changing lifestyles and
      the growth of the middle-class. In this essay we discuss how the practice of
      Nature Cure provides a way of understanding the scale and scope of the crisis, as
      it is embodied, and a way to understand key elements of a solution to problems
      that the crisis presents for institutionalized health care. As institutionalized
      in contemporary India, Nature Cure involves treatment and managed care using
      earth, air, sunlight, and water as well as a strict dietary regimen. In this
      regard, the essay shows how Nature Cure's bio-ecological orientation toward
      public health, which is grounded in the history of its modern incorporation into
      India, provides an expansionist, ecological model for holistic care that counters
      the reductionist logic of bio-medical pharmaceuticalization.

PMID- 29215550
TI  - Poly-gamma-glutamic Acid Synthesis, Gene Regulation, Phylogenetic Relationships,
      and Role in Fermentation.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is a biodegradable biopolymer produced by
      several bacteria, including Bacillus subtilis and other Bacillus species; it has
      good biocompatibility, is non-toxic, and has various potential biological
      applications in the food, pharmaceutical, cosmetic, and other industries. In this
      review, we have described the mechanisms of gamma-PGA synthesis and gene
      regulation, its role in fermentation, and the phylogenetic relationships among
      various pgsBCAE, a biosynthesis gene cluster of gamma-PGA, and pgdS, a
      degradation gene of gamma-PGA. We also discuss potential applications of gamma
      PGA and highlight the established genetic recombinant bacterial strains that
      produce high levels of gamma-PGA, which can be useful for large-scale gamma-PGA
      production.

PMID- 29215551
TI  - CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma
      Patients.
AB  - The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin
      receptor 2 (ANTXR2), is a transmembrane protein putatively involved in
      extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes
      endothelial cell proliferation and exhibits angiogenic properties. Its
      downregulation is associated with a worsened survival of breast carcinoma
      patients. Aim of this study was to analyze the CMG2 mRNA and protein expression
      in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was
      measured in 121 tumor samples of soft tissue sarcoma patients using quantitative
      real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA
      was significantly correlated with the corresponding CMG2 protein expression (rs =
      0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions
      of several ECM and tissue remodeling enzymes, among them CD26 and components of
      the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients'
      disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25
      vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2
      expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2
      may be an interesting candidate gene for the further exploration of soft tissue
      sarcoma genesis and progression.

PMID- 29215552
TI  - Two Distinct Clinical Courses of Human Cowpox, Germany, 2015.
AB  - Here we present two cases of human infection with cowpox virus with distinct
      clinical courses. A series of clinical photographs documents lesion progression
      over time. In the first case-an unvaccinated young veterinary assistant-a pustule
      was treated locally with cortisone. The lesion turned into a large ulcer
      accompanied by severe lymphadenitis. Based on her close contact to a sick stray
      cat, infection with cowpox virus was assumed and confirmed by virus isolation,
      PCR, and serology. The clinical course took up to eleven months until healing of
      the wound was complete. Transmission of cowpox virus from the cat was likely
      because a skin swab was PCR-positive and the cat had a high titer of anti
      orthopoxvirus antibodies. In contrast, a rather mild clinical course of cowpox
      was confirmed in a 49-year-old male farmer vaccinated against smallpox. Only a
      small eschar developed, and wound closure was complete after 6 weeks.

PMID- 29215553
TI  - Anti-Diabetic Effect of Organo-Chalcogen (Sulfur and Selenium) Zinc Complexes
      with Hydroxy-Pyrone Derivatives on Leptin-Deficient Type 2 Diabetes Model ob/ob
      Mice.
AB  - Since the discovery of the anti-diabetic effects of zinc (Zn) complex, we
      synthesized several Zn complexes and evaluated their effects using the KKAy type
      2 diabetes mouse model. Recently, we demonstrated that organo-chalcogen (sulfur
      and selenium) Zn complexes elicit strong anti-diabetic effects. In this study, we
      treated leptin-deficient ob/ob mice with organo-chalcogen Zn complexes, and
      evaluated the resulting anti-diabetic effects in a mouse model of diabetes
      arising from pathogenic mechanisms different from those in KKAy mice. C57BL/6J
      ob/ob mice orally received either bis(3-hydroxy-2-methyl-4(H)-pyran-4-thiono)Zn,
      [Zn(hmpt)2] or bis(3-hydroxy-2-methyl-4(H)-pyran-4-seleno)Zn, [Zn(hmps)2], daily
      for 28 days. Both Zn complexes elicited potent blood glucose-lowering effects and
      improved HbA1c values. Moreover, glucose intolerance improved as evidenced by the
      oral glucose tolerance test, and fasting plasma insulin levels decreased in both
      types of Zn complex-treated mice. Zn concentrations in the liver and pancreas of
      [Zn(hmpt)2]-treated mice and in the pancreas of [Zn(hmps)2]-treated mice were
      increased, respectively. The results suggest that the present Zn complexes mainly
      exerted an anti-diabetic effect in the liver or pancreas. This study is the first
      to demonstrate that potent Zn complexes elicit anti-diabetic effects in not only
      KKAy but also ob/ob mice via a normalizing effect on insulin secretion and
      fasting blood glucose levels.

PMID- 29215554
TI  - Pets, Purity and Pollution: Why Conventional Models of Disease Transmission Do
      Not Work for Pet Rat Owners.
AB  - In the United Kingdom, following the emergence of Seoul hantavirus in pet rat
      owners in 2012, public health authorities tried to communicate the risk of this
      zoonotic disease, but had limited success. To explore this lack of engagement
      with health advice, we conducted in-depth, semi-structured interviews with pet
      rat owners and analysed them using a grounded theory approach. The findings from
      these interviews suggest that rat owners construct their pets as different from
      wild rats, and by elevating the rat to the status of a pet, the powerful
      associations that rats have with dirt and disease are removed. Removing the rat
      from the contaminated outside world moves their pet rat from being 'out of place'
      to 'in place'. A concept of 'bounded purity' keeps the rat protected within the
      home, allowing owners to interact with their pet, safe in the knowledge that it
      is clean and disease-free. Additionally, owners constructed a 'hierarchy of
      purity' for their pets, and it is on this structure of disease and risk that
      owners base their behaviour, not conventional biomedical models of disease.

PMID- 29215555
TI  - The Effect of Branding to Promote Healthy Behavior: Reducing Tobacco Use among
      Youth and Young Adults.
AB  - Policy interventions such as public health mass media campaigns disseminate
      messages in order to improve health-related knowledge, attitudes, beliefs and
      behaviors at the population level. Only more recently have campaigns that promote
      health-related behaviors adopted branding, a well-established marketing strategy,
      to influence how consumers think and feel about a message. This study examines
      whether positive brand equity for the national truth(r) campaign is associated
      with lower likelihood of cigarette use over time using the nationally
      representative Truth Longitudinal Cohort of youth and young adults, aged 15-21.
      Logistic regression models were used to examine the relationship between brand
      equity and the likelihood of reporting past 30-day smoking over a 12-month
      period. Respondents who reported positive brand equity were significantly less
      likely to report past 30-day smoking 12 months later (OR = 0.66, p < 0.05),
      controlling for covariates known to influence tobacco use behavior. Findings also
      translate the effect size difference to a population estimate of more than
      300,000 youth and young adults having been prevented from current smoking over
      the course of a year. Building brand equity is a strategic process for health
      promotion campaigns, not only to improve message recall and salience but also to
      influence behavioral outcomes.

PMID- 29215556
TI  - Mutual Effects of Fluorine Dopant and Oxygen Vacancies on Structural and
      Luminescence Characteristics of F Doped SnO2 Nanoparticles.
AB  - SnO2 and F doped SnO2 (FTO) nanoparticles (NPs) have been synthesized by the
      hydrothermal method with subsequent annealing at 500  degrees C. The
      microstructure and photoluminescence (PL) property of SnO2 and FTO NPs have been
      investigated, and an assumption model about the luminescence process of FTO NPs
      has been proposed. All of the SnO2 and FTO NPs possess polycrystalline tetragonal
      rutile structures, and the average size in the range of 16.5-20.2 nm decreases
      with the increasing of F doping content. The doping element F is shown a
      uniformly distribution by electron energy loss spectroscopy (EELS) mapping. The
      oxygen vacancy concentration becomes higher as is verified by Raman and X-ray
      photoelectron spectra (XPS). There are three kinds of oxygen chemical states in
      SnO2 and FTO NPs, in which Oalpha corresponds to oxygen vacancies. The room
      temperature PL position is observed to be independent of F doping content. F- may
      substitute O2- into the SnO2 lattice by generating F O + and one extra e-, which
      can combine with V O + or V O + + to generate V O 0 or V O + to ensure charge
      balance.

PMID- 29215557
TI  - Indoors Locality Positioning Using Cognitive Distances and Directions.
AB  - Spatial relationships are crucial to spatial knowledge representation, such as
      positioning localities. However, minimal attention has been devoted to
      positioning localities indoors with locality description. Distance and direction
      relations are generally used when positioning localities, namely, translating
      descriptive localities into spatially explicit ones. We propose a joint
      probability function to model locality distribution to address the uncertainty of
      positioning localities. The joint probability function consists of distance and
      relative direction membership functions. We propose definitions and restrictions
      for the use of the joint probability function to make the locality distribution
      highly practical. We also evaluate the performance of our approach through indoor
      experiments. Test results demonstrate that a positioning accuracy of 3.5 m can be
      achieved with the semantically derived spatial relationships.

PMID- 29215559
TI  - Two Interrogated FBG Spectral Linewidth for Strain Sensing through Correlation.
AB  - The spectral linewidth from two cross-correlated fiber Bragg gratings (FBGs) are
      interrogated and characterized using a delayed self-homodyne method for fiber
      strain sensing. This approach employs a common higher frequency resolution
      instead of wavelength. A sensitivity and resolution of 166 MHz/MUepsilon and 50
      nepsilon were demonstrated from 4 GHz spectral linewidth characterization on the
      electric spectrum analyzer. A 10 nepsilon higher resolution can be expected
      through random noise analyses when the spectral linewidth from two FBG
      correlations is reduced to 1 GHz. Moreover, the FBG spectrum is broadened during
      strain and experimentally shows a 0.44 pm/MUepsilon sensitivity, which is mainly
      caused by the photo elastic effect from the fiber grating period stretch.

PMID- 29215558
TI  - Synthesis of Benzyl Acetate Catalyzed by Lipase Immobilized in Nontoxic Chitosan
      Polyphosphate Beads.
AB  - Enzymes serve as biocatalysts for innumerable important reactions, however, their
      application has limitations, which can in many cases be overcome by using
      appropriate immobilization strategies. Here, a new support for immobilizing
      enzymes is proposed. This hybrid organic-inorganic support is composed of
      chitosan-a natural, nontoxic, biodegradable, and edible biopolymer-and sodium
      polyphosphate as the inorganic component. Lipase B from Candida antarctica (CALB)
      was immobilized on microspheres by encapsulation using these polymers. The
      characterization of the composites (by infrared spectroscopy, thermogravimetric
      analysis, and confocal Raman microscopy) confirmed the hybrid nature of the
      support, whose external part consisted of polyphosphate and core was composed of
      chitosan. The immobilized enzyme had the following advantages: possibility of
      enzyme reuse, easy biocatalyst recovery, increased resistance to variations in
      temperature (activity declined from 60  degrees C and the enzyme was inactivated
      at 80  degrees C), and increased catalytic activity in the transesterification
      reactions. The encapsulated enzymes were utilized as biocatalysts for
      transesterification reactions to produce the compound responsible for the aroma
      of jasmine.

PMID- 29215560
TI  - Multi-Component One-Pot Reaction of Aromatic Carbonyl Compounds, Tosylhydrazide,
      and Arylboronic Acids.
AB  - In this paper, we developed a new method using 4-bromoacetophenone as the
      starting material, with tosylhydrazide and two arylboronic acids using Barluenga
      and Suzuki couplings in a four-component one-pot reaction to afford the target
      product 4-benzyl-1,1'-biphenyls. This system that we have developed enables the
      use of easily accessible starting materials and can be employed on a wide variety
      of substrates with good functional group tolerance. In particular, this protocol
      can be applied to the synthesis of 4-(1-([1,1'-biphenyl]-4-yl)ethyl)pyridine
      derivatives, a class of potential analogs of CPY17 inhibitors of prostate cancer.

PMID- 29215561
TI  - Link Connectivity and Coverage of Underwater Cognitive Acoustic Networks under
      Spectrum Constraint.
AB  - Extensive attention has been given to the use of cognitive radio technology in
      underwater acoustic networks since the acoustic spectrum became scarce due to the
      proliferation of human aquatic activities. Most of the recent studies on
      underwater cognitive acoustic networks (UCANs) mainly focus on spectrum
      management or protocol design. Few efforts have addressed the quality-of-service
      (QoS) of UCANs. In UCANs, secondary users (SUs) have lower priority to use
      acoustic spectrum than primary users (PUs) with higher priority to access
      spectrum. As a result, the QoS of SUs is difficult to ensure in UCANs. This paper
      proposes an analytical model to investigate the link connectivity and the
      probability of coverage of SUs in UCANs. In particular, this model takes both
      topological connectivity and spectrum availability into account, though spectrum
      availability has been ignored in most recent studies. We conduct extensive
      simulations to evaluate the effectiveness and the accuracy of our proposed model.
      Simulation results show that our proposed model is quite accurate. Besides, our
      results also imply that the link connectivity and the probability of coverage of
      SUs heavily depend on both the underwater acoustic channel conditions and the
      activities of PUs.

PMID- 29215562
TI  - Improved Performance of Magnetic Cross-Linked Lipase Aggregates by Interfacial
      Activation: A Robust and Magnetically Recyclable Biocatalyst for
      Transesterification of Jatropha Oil.
AB  - Lipases are the most widely employed enzymes in commercial industries. The
      catalytic mechanism of most lipases involves a step called "interfacial
      activation". As interfacial activation can lead to a significant increase in
      catalytic activity, it is of profound importance in developing lipase
      immobilization methods. To obtain a potential biocatalyst for industrial
      biodiesel production, an effective strategy for enhancement of catalytic activity
      and stability of immobilized lipase was developed. This was performed through the
      combination of interfacial activation with hybrid magnetic cross-linked lipase
      aggregates. This biocatalyst was investigated for the immobilization of lipase
      from Rhizomucor miehei (RML). Under the optimal conditions, the activity recovery
      of the surfactant-activated magnetic RML cross-linked enzyme aggregates (CLEAs)
      was as high as 2058%, with a 20-fold improvement over the free RML. Moreover, the
      immobilized RML showed excellent catalytic performance for the biodiesel reaction
      at a yield of 93%, and more importantly, could be easily separated from the
      reaction mixture by simple magnetic decantation, and retained more than 84% of
      its initial activities after five instances of reuse. This study provides a new
      and versatile approach for designing and fabricating immobilized lipase with high
      activation and stability.

PMID- 29215563
TI  - Response of Ustilago maydis against the Stress Caused by Three Polycationic
      Chitin Derivatives.
AB  - Chitosan is a stressing molecule that affects the cells walls and plasma membrane
      of fungi. For chitosan derivatives, the action mode is not clear. In this work,
      we used the yeast Ustilago maydis to study the effects of these molecules on the
      plasma membrane, focusing on physiologic and stress responses to chitosan (CH),
      oligochitosan (OCH), and glycol-chitosan (GCH). Yeasts were cultured with each of
      these molecules at 1 mg.mL-1 in minimal medium. To compare plasma membrane
      damage, cells were cultivated in isosmolar medium. Membrane potential (Deltapsi)
      as well as oxidative stress were measured. Changes in the total plasma membrane
      phospholipid and protein profiles were analyzed using standard methods, and
      fluorescence-stained mitochondria were observed. High osmolarity did not protect
      against CH inhibition and neither affected membrane potential. The OCH did
      produce higher oxidative stress. The effects of these molecules were evidenced by
      modifications in the plasma membrane protein profile. Also, mitochondrial damage
      was evident for CH and OCH, while GCH resulted in thicker cells with fewer
      mitochondria and higher glycogen accumulation.

PMID- 29215564
TI  - Piezoelectric Potential in Single-Crystalline ZnO Nanohelices Based on Finite
      Element Analysis.
AB  - Electric potential produced in deformed piezoelectric nanostructures is of
      significance for both fundamental study and practical applications. To reveal the
      piezoelectric property of ZnO nanohelices, the piezoelectric potential in single
      crystal nanohelices was simulated by finite element method calculations. For a
      nanohelix with a length of 1200 nm, a mean coil radius of 150 nm, five active
      coils, and a hexagonal coiled wire with a side length 100 nm, a compressing force
      of 100 nN results in a potential of 1.85 V. This potential is significantly
      higher than the potential produced in a straight nanowire with the same length
      and applied force. Maintaining the length and increasing the number of coils or
      mean coil radius leads to higher piezoelectric potential in the nanohelix.
      Appling a force along the axial direction produces higher piezoelectric potential
      than in other directions. Adding lateral forces to an existing axial force can
      change the piezoelectric potential distribution in the nanohelix, while the
      maximum piezoelectric potential remains largely unchanged in some cases. This
      research demonstrates the promising potential of ZnO nanohelices for applications
      in sensors, micro-electromechanical systems (MEMS) devices, nanorobotics, and
      energy sciences.

PMID- 29215565
TI  - A Miniaturized Impedimetric Immunosensor for the Competitive Detection of
      Adrenocorticotropic Hormone.
AB  - Adrenocorticotropic hormone (ACTH) plays an essential role in regulating
      corticosteroid hormone production, which has important functions in a myriad of
      critical physiological functions. In this proof-of-concept study, a miniaturized
      immunosensor was developed for the highly sensitive detection of ACTH using
      electrochemical impedance spectroscopy (EIS) in connection with disposable screen
      printed gold electrodes (SPGEs). A film of 3,3'
      dithiobis[sulfosuccinimidylpropionate] (DTSSP) was prepared to immobilize anti
      ACTH antibodies covalently on the nanostructured SPGE surface. The surface
      immobilized anti-ACTH antibodies captured the biotinylated ACTH (biotin-ACTH) and
      non-labelled ACTH for the competitive immunoassay. After coupling of a
      streptavidin-alkaline phosphatase conjugate (Streptavidin-ALP), the bio-catalysed
      precipitation of an insoluble and insulating product onto the sensing interface
      changed the charge transfer resistance (Rct) characteristics significantly. The
      detection limit of 100 fg/mL was determined for ACTH in a 5 MUL sample volume,
      which indicated that this versatile platform can be easily adapted for
      miniaturized electrochemical immunosensing of cancer marker biomolecules. High
      selectivity and sensitivity of our immunoassay to detect ACTH in real samples
      demonstrated its promising potential for future development and applications
      using clinical samples.

PMID- 29215566
TI  - Multi-Family Pediatric Pain Group Therapy: Capturing Acceptance and Cultivating
      Change.
AB  - Behavioral health interventions for pediatric chronic pain include cognitive
      behavioral (CBT), acceptance and commitment (ACT), and family-based therapies,
      though literature regarding multi-family therapy (MFT) is sparse. This
      investigation examined the utility and outcomes of the Courage to Act with Pain:
      Teens Identifying Values, Acceptance, and Treatment Effects (CAPTIVATE) program,
      which included all three modalities (CBT, ACT, MFT) for youth with chronic pain
      and their parents. Program utility, engagement, and satisfaction were evaluated
      via quantitative and qualitative feedback. Pain-specific psychological,
      behavioral, and interpersonal processes were examined along with outcomes related
      to disability, quality of life, pain interference, fatigue, anxiety, and
      depressive symptoms. Participants indicated that CAPTIVATE was constructive,
      engaging, and helpful for social and family systems. Clinical and statistical
      improvements with large effect sizes were captured for pain catastrophizing,
      acceptance, and protective parenting but not family functioning. Similar effects
      were found for functional disability, pain interference, fatigue, anxiety, and
      depression. Given the importance of targeting multiple systems in the management
      of pediatric chronic pain, preliminary findings suggest a potential new group
      based treatment option for youth and families. Next steps involve evaluating the
      differential effect of the program over treatment as usual, as well as specific
      CBT, ACT, and MFT components and processes that may affect outcomes.

PMID- 29215567
TI  - Are Pericentric Inversions Reorganizing Wedge Shell Genomes?
AB  - Wedge shells belonging to the Donacidae family are the dominant bivalves in
      exposed beaches in almost all areas of the world. Typically, two or more
      sympatric species of wedge shells differentially occupy intertidal, sublittoral,
      and offshore coastal waters in any given locality. A molecular cytogenetic
      analysis of two sympatric and closely related wedge shell species, Donax
      trunculus and Donax vittatus, was performed. Results showed that the karyotypes
      of these two species were both strikingly different and closely alike; whilst
      metacentric and submetacentric chromosome pairs were the main components of the
      karyotype of D. trunculus, 10-11 of the 19 chromosome pairs were telocentric in
      D. vittatus, most likely as a result of different pericentric inversions. GC-rich
      heterochromatic bands were present in both species. Furthermore, they showed
      coincidental 45S ribosomal RNA (rRNA), 5S rRNA and H3 histone gene clusters at
      conserved chromosomal locations, although D. trunculus had an additional 45S rDNA
      cluster. Intraspecific pericentric inversions were also detected in both D.
      trunculus and D. vittatus. The close genetic similarity of these two species
      together with the high degree of conservation of the 45S rRNA, 5S rRNA and H3
      histone gene clusters, and GC-rich heterochromatic bands indicate that
      pericentric inversions contribute to the karyotype divergence in wedge shells.

PMID- 29215569
TI  - The Effect of Feed Form on Diet Digestibility and Cecal Parameters in Rabbits.
AB  - Fifteen New Zealand rabbits were randomly assigned to one of 3 dietary treatment
      groups of 5 animals each and fed pelleted, extruded, or muesli diets in a
      completely randomized design experiment. Rabbits were placed in individual cages
      with ad libitum access to water and food for 45 days acclimation followed by 30
      days experimental period. Feed intake of rabbits fed pelleted and extruded diets
      was greater (p < 0.05) than rabbits fed the muesli diet (125.6 and 130.4 vs. 91.9
      g/d), but weight change and feed efficiency were not affected by treatment. Diet
      digestibility among the treatments was inconsistent when comparing results
      obtained from total fecal collection and AIA (please define) as an internal
      marker. Rabbits fed extruded and pelleted diets had lower (p < 0.05) cecal pH
      (6.42 and 6.38 vs. 7.02, respectively), and higher (p < 0.05) production of SCFA
      (18.5 and 19.0 vs. 11.7 mM, respectively) than those fed muesli. The fermentation
      products from rabbits fed pelleted and extruded diets had a greater proportion of
      butyrate and less propionate than rabbits fed muesli. The results of this study
      indicate that the basal dietary composition had a greater impact on diet
      utilization and cecal fermentation than food form.

PMID- 29215568
TI  - Influenza A Virus M2 Protein: Roles from Ingress to Egress.
AB  - Influenza A virus (IAV) matrix protein 2 (M2) is among the smallest bona fide,
      hence extensively studied, ion channel proteins. The M2 ion channel activity is
      not only essential for virus replication, but also involved in modulation of
      cellular homeostasis in a variety of ways. It is also the target for ion channel
      inhibitors, i.e., anti-influenza drugs. Thus far, several studies have been
      conducted to elucidate its biophysical characteristics, structure-function
      relationships of the ion channel, and the M2-host interactome. In this review, we
      discuss M2 protein synthesis and assembly into an ion channel, its roles in IAV
      replication, and the pathophysiological impact on the host cell.

PMID- 29215571
TI  - Application of the Superelastic NiTi Spring in Ankle Foot Orthosis (AFO) to
      Create Normal Ankle Joint Behavior.
AB  - Hinge-based Ankle Foot Orthosis (HAFO) is one of the most common non-surgical
      solutions for the foot drop. In conventional HAFOs, the ankle joint is almost
      locked, and plantar flexion is restricted due to the high stiffness of the hinge
      mechanism. This often leads to a rigid walking gate cycle, poor muscle activity,
      and muscle atrophy. Since the ankle torque-angle loop has a non-linear profile,
      the use of a superelastic NiTi spring within the hinge, due to its nonlinear
      behavior, could recreate a close-to-normal stiffness of the normal ankle joint,
      which, in turn, could create a more natural walk. The focus of this study is to
      evaluate the performance of a superelastic NiTi spring versus a conventional
      Stainless Steel spring in a hinge mechanism of a custom-fit HAFO. To this aim, a
      custom-fit HAFO was fabricated via the fast casting technique. Then, motion
      analysis was performed for two healthy subjects (Case I and Case II): (i)
      subjects with bare foot; (ii) subjects wearing a conventional HAFO with no
      spring; (iii) subjects wearing a conventional Stainless Steel-based HAFO; and
      (iv) subjects wearing a NiTi spring-based HAFO. The data related to the ankle
      angle and the amount of moment applied to the ankle during walking were recorded
      using Cortex software and used for the evaluations. Finally, Finite Element
      Analysis (FEA) was performed to evaluate the safety of the designed HAFO. The
      NiTi spring offers a higher range of motion (7.9 versus 4.14 degree) and an
      increased level of moment (0.55 versus 0.36 N.m/kg). Furthermore, a NiTi spring
      offers an ankle torque-angle loop closer to that of the healthy subjects.

PMID- 29215570
TI  - Host Cell Restriction Factors that Limit Influenza A Infection.
AB  - Viral infection of different cell types induces a unique spectrum of host defence
      genes, including interferon-stimulated genes (ISGs) and genes encoding other
      proteins with antiviral potential. Although hundreds of ISGs have been described,
      the vast majority have not been functionally characterised. Cellular proteins
      with putative antiviral activity (hereafter referred to as "restriction factors")
      can target various steps in the virus life-cycle. In the context of influenza
      virus infection, restriction factors have been described that target virus entry,
      genomic replication, translation and virus release. Genome wide analyses, in
      combination with ectopic overexpression and/or gene silencing studies, have
      accelerated the identification of restriction factors that are active against
      influenza and other viruses, as well as providing important insights regarding
      mechanisms of antiviral activity. Herein, we review current knowledge regarding
      restriction factors that mediate anti-influenza virus activity and consider the
      viral countermeasures that are known to limit their impact. Moreover, we consider
      the strengths and limitations of experimental approaches to study restriction
      factors, discrepancies between in vitro and in vivo studies, and the potential to
      exploit restriction factors to limit disease caused by influenza and other
      respiratory viruses.

PMID- 29215572
TI  - Development of Octyl Methoxy Cinnamates (OMC)/Silicon Dioxide (SiO2)
      Nanoparticles by Sol-Gel Emulsion Method.
AB  - Although octyl methoxy cinnamates (OMC) is the most used Ultraviolet B (UVB)
      filter in sunscreen, it has poor light stability in emulsion system. In this
      study, OMC/SiO2 nanoparticles were prepared via sol-gel emulsion method.
      Tetraethoxy silane (TEOS) was used as the silica source to encapsulate OMC.
      Modification of experimental parameters such as stirring speed of condensation
      reaction and emulsion condition, pH value of acid-catalyzed, surfactant and
      different percentage of TEOS and OMC, adding of OMC and surfactant to different
      phase may affect the particle size, and yield and entrapment efficiency in
      preparation process of OMC/SiO2 nanoparticles. Concluding all the parameter, we
      found that when condensation reaction and emulsion conditions are at 1000 rpm, pH
      1.5, Span 80/Tween 20, TEOS/OMC ratios 1:1, OMC and surfactants added in oil
      phase, resulting in smaller particle sizes 476.5 nm, higher yield 95.8%, and
      higher entrapment efficiency 61.09%. Fourier transform infrared (FTIR) analysis
      demonstrated that OMC/SiO2 nanoparticles were successfully prepared. In vitro
      release profile supposed that OMC/SiO2 nanoparticles can delay OMC releasing and
      had 60.83% decreasing of cumulative amount. Therefore, the OMC/SiO2 nanoparticles
      have the potential to develop as new sunscreen materials in the use for cosmetics
      field in the future.

PMID- 29215573
TI  - The Use of Liposomes and Nanoparticles as Drug Delivery Systems to Improve Cancer
      Treatment in Dogs and Cats.
AB  - BACKGROUND: Cancer remains a leading cause of death in companion animals. In
      human medicine, liposomes and nanoparticles have been extensively investigated as
      drug delivery systems (DDS) for anticancer agents due to their ability to target
      cancerous cells and reduce the negative side effects of free cytostatic drugs. In
      this review, the authors discuss the results of clinical trials using liposomes
      and polymer-based nanoparticles as DDS to improve cancer treatment in dogs and
      cats, indicating which ones seem worth further evaluation. The authors then
      overview ongoing animal cancer clinical trials, evaluating nano-DDS registered on
      the American Veterinary Medical Association Animal Health Studies Database.
      Finally, the authors indicate the nano-drugs that require further in vivo
      evaluation based on the encouraging results obtained from in vitro studies.
      CONCLUSIONS: Liposomes have been the most investigated nano-DDS in veterinary
      medicine. The lack of cardiotoxicity of the commercially available liposomal
      doxorubicin (Doxil/Caelyx) suggests it should be used in dogs with cardiac
      disorders, rather than using free doxorubicin. Cisplatin-incorporated hyaluronic
      acid nanoparticles, nanocrystals of cisplatin, and paclitaxel are the most
      promising nano-drugs for potent applications in treating various canine cancers
      (e.g. oral melanoma, oral sarcoma, and anal gland adenocarcinoma) and their
      translation into the treatment of human diseases.

PMID- 29215574
TI  - Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones.
AB  - : Plant polyphenols have been highlighted not only as chemopreventive, but also
      as potential anticancer substances. Flavones are a subclass of natural flavonoids
      reported to have an antioxidant and anticancer activity. The aim of our study was
      to evaluate antioxidant and anticancer activity of seventeen trihydroxyflavone
      derivatives, including apigenin (API) and baicalein (BCL). Also, we wanted to
      find out if there is a correlation between those two effects. Cell growth
      inhibition testing was carried out using MTT assay in three different human
      cancer cell lines: lung (A549), breast (MCF-7) and brain epithelial (U87).
      Antioxidant activity was determined by the DPPH radical scavenging method.
      Thirteen trihydroxyflavones possessed anticancer activity against at least one
      tested cancer cell line. They were more active against the MCF-7 cell line, and
      the lowest activity was determined against the U87 cell line. The majority of
      compounds inhibited cancer cell growth at EC50 values between 10-50 uM. The most
      active compound was 3',4',5-trihydroxyflavone 7, especially against A549 and MCF
      7 cell lines. The correlation between anti-proliferative and antioxidant activity
      was only moderate, and it was determined for A549 and U87 cancer cell lines. The
      most important fragment for those two effects is the ortho-dihydroxy group in
      ring B. CONCLUSIONS: Trihydroxyflavones demonstrated anticancer activity. Further
      and more detailed studies should to be carried out to estimate the structure
      activity relationship of these compounds.

PMID- 29215575
TI  - Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by
      Inhibiting Rad52.
AB  - Effective DNA repair enables cancer cells to survive DNA damage induced by
      chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair
      pathways is a promising therapeutic strategy for increasing the efficacy of such
      treatments. In this study, we found that dihydrocoumarin (DHC), a flavoring
      agent, causes deficiencies in double-stand break (DSB) repair and prolonged DNA
      damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was
      revealed to be inhibited by DHC, which results in deficiencies in DSB repair and
      prolonged DNA damage checkpoint recovery. The deletion of RPD3, a class I histone
      deacetylase (HDAC), was found to mimic DHC-induced suppression of Rad52
      expression, suggesting that the HDAC inhibitor activity of DHC is critical to DSB
      repair and DNA damage sensitivity. Overall, our findings delineate the regulatory
      mechanisms of DHC in DSB repair and suggest that it might potentially be used as
      an inhibitor of the DNA repair pathway in human cells.

PMID- 29215577
TI  - Acute Encephalitis in an Adult with Diffuse Large B-Cell Lymphoma with Secondary
      Involvement of the Central Nervous System: Infectious or Non-Infectious Etiology?
AB  - Both infectious and non-infectious etiologies of acute encephalitis have been
      described, as well as their specific presentations, diagnostic tests, and
      therapies. Classic findings of acute encephalitis include altered mental status,
      fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report
      an interesting case of a 61-year-old male with a history of diffuse large B-cell
      lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL).
      He presented with acute encephalitis: altered mental status, fever, leukocytosis,
      neuropsychiatric symptoms, multiple unchanged brain lesions on computed
      tomography scan of the head, and EEG showed mild to moderate diffuse slowing with
      low-moderate polymorphic delta and theta activity. With such a wide range of
      symptoms, the differential diagnosis included paraneoplastic and autoimmune
      encephalitis. Infectious and autoimmune/paraneoplastic encephalitis in patients
      with SCNS-DLBCL are not well documented in the literature, hence diagnosis and
      therapy becomes challenging. This case report describes the patient's unique
      presentation of acute encephalitis.

PMID- 29215576
TI  - Fasting Plasma Glucose, Self-Appraised Diet Quality and Depressive Symptoms: A US
      Representative Cross-Sectional Study.
AB  - Depression and type 2 diabetes (T2D) contribute significantly to global burden of
      disease and often co-occur. Underpinning type 2 diabetes is poor glycaemic
      control and glucose is also an obligatory substrate for brain metabolism, with
      potential implications for cognition, motivation and mood. This research aimed to
      examine the relationships between fasting plasma glucose and depressive symptoms
      in a large, population representative sample of US adults, controlling for other
      demographic and lifestyle behavioural risk factors. Using the 2013-2014 National
      Health and Nutrition Examination Survey (NHANES) data, this study first
      investigated the relationship between fasting plasma glucose and mental disorders
      at a population-level, accounting for demographic, health behavioural and weight
      related factors known to co-occur with both type 2 diabetes and mental disorders.
      Depressive symptoms were derived from the 9-item Patient Health Questionnaire.
      Fasting plasma glucose was obtained through medical examination and demographic
      (age, household income, sex) and health characteristics (perceived diet quality,
      daily time sedentary) were self-reported. Body mass index was calculated from
      objectively measured height and weight. In the univariate model, higher fasting
      plasma glucose was associated with greater depressive symptoms among females (b =
      0.24, 95% CI = 0.05, 0.43, p < 0.05), but not males. In the final fully adjusted
      model, the relationship between fasting plasma glucose and depressive symptoms
      was non-significant for both males and females. Of all independent variables,
      self-appraised diet quality was strongly and significantly associated with
      depressive symptoms and this remained significant when individuals with diabetes
      were excluded. Although diet quality was self-reported based on individuals'
      perceptions, these findings are consistent with a role for poor diet in the
      relationship between fasting plasma glucose and depressive symptoms.

PMID- 29215578
TI  - Evaluation of Antibiotic Residues in Raw Meat Using Different Analytical Methods.
AB  - Antibiotic residue in meat is a serious public health concern due to its harmful
      effects on consumer health. This study aimed at estimating the residue levels of
      four commonly used antibiotics in meat samples using three analytical methods
      (ELISA, TLC and HPLC). A total of 150 samples of raw meat from sales points were
      analysed for ciprofloxacin, streptomycin, tetracycline, and sulphanilamide
      residues. Overall, ELISA analysis showed that 56, 34, 18, and 25.3% of the
      samples tested positive for ciprofloxacin, streptomycin, sulphanilamide and
      tetracycline residues respectively while TLC and HPLC detected 21.4, 29.4, 92.5,
      and 14.6%, and 8.3, 41.1, 88.8, and 14.6% of the samples as containing the
      residues, with ciprofloxacin and sulphanilamide having the lowest and highest
      occurrence, respectively. Furthermore, the concentrations of antibiotic residues
      were in the ranges of 19.8-92.8, 26.6-489.1, 14.2-1280.8, and 42.6-355.6 MUg/kg
      with ELISA, while HPLC detected concentration ranges of 20.7-82.1, 41.8-320.8,
      65.2-952.2 and 32.8-95.6 MUg/kg for sulphanilamide, tetracycline, streptomycin,
      and ciprofloxacin, respectively. Mean ciprofloxacin and streptomycin residue
      levels were above the Codex/SA MRL recommended limit, while 3% of the samples
      contained multidrug residues. Although some of the mean residues levels were
      below the permissible limits, the co-occurrence of multidrug residues in some of
      the samples calls for concern.

PMID- 29215580
TI  - Adsorption of Pb(II) and Cu(II) by Ginkgo-Leaf-Derived Biochar Produced under
      Various Carbonization Temperatures and Times.
AB  - Ginkgo trees are common street trees in Korea, and the large amounts of leaves
      that fall onto the streets annually need to be cleaned and treated. Therefore,
      fallen gingko leaves have been used as a raw material to produce biochar for the
      removal of heavy metals from solutions. Gingko-leaf-derived biochar was produced
      under various carbonization temperatures and times. This study evaluated the
      physicochemical properties and adsorption characteristics of gingko-leaf-derived
      biochar samples produced under different carbonization conditions regarding
      Pb(II) and Cu(II). The biochar samples that were produced at 800  degrees C for
      90 and 120 min contained the highest oxygen- and nitrogen-substituted carbons,
      which might contribute to a high metal-adsorption rate. The intensity of the
      phosphate bond was increased with the increasing of the carbonization temperature
      up to 800  degrees C and after 90 min of carbonization. The Pb(II) and Cu(II)
      adsorption capacities were the highest when the gingko-leaf-derived biochar was
      produced at 800  degrees C, and the removal rates were 99.2% and 34.2%,
      respectively. The highest removal rate was achieved when the intensity of the
      phosphate functional group in the biochar was the highest. Therefore, the gingko
      leaf-derived biochar produced at 800  degrees C for 90 min can be used as an
      effective bio-adsorbent in the removal of metals from solutions.

PMID- 29215579
TI  - The Potential of Indonesian Heterobranchs Found around Bunaken Island for the
      Production of Bioactive Compounds.
AB  - The species diversity of marine heterobranch sea slugs found on field trips
      around Bunaken Island (North Sulawesi, Indonesia) and adjacent islands of the
      Bunaken National Marine Park forms the basis of this review. In a survey
      performed in 2015, 80 species from 23 families were collected, including 17 new
      species. Only three of these have been investigated previously in studies from
      Indonesia. Combining species diversity with a former study from 2003 reveals in
      total 140 species from this locality. The diversity of bioactive compounds known
      and yet to be discovered from these organisms is summarized and related to the
      producer if known or suspected (might it be down the food chain, de novo
      synthesised from the slug or an associated bacterium). Additionally, the
      collection of microorganisms for the discovery of natural products of
      pharmacological interest from this hotspot of biodiversity that is presented here
      contains more than 50 species that have never been investigated before in regard
      to bioactive secondary metabolites. This highlights the great potential of the
      sea slugs and the associated microorganisms for the discovery of natural products
      of pharmacological interest from this hotspot of biodiversity.

PMID- 29215581
TI  - Stress-Induced Hyperglycemia in Diabetes: A Cross-Sectional Analysis to Explore
      the Definition Based on the Trauma Registry Data.
AB  - Background: The diagnosis of diabetic hyperglycemia (DH) does not preclude a
      diabetes patient from having a stress-induced hyperglycemic response. This study
      aimed to define the optimal level of elevated glucose concentration for
      determining the occurrence of stress-induced hyperglycemia (SIH) in patients with
      diabetes. Methods: This retrospective study reviewed the data of all hospitalized
      trauma patients, in a Level I trauma center, from 1 January 2009 to 31 December
      2016. Only adult patients aged >=20 years, with available data on serum glucose
      and glycated hemoglobin A1c (HbA1c) levels upon admission, were included in the
      study. Long-term average glucose levels, as A1c-derived average glucose (ADAG),
      using the equation, ADAG = ((28.7 * HbA1c) - 46.7), were calculated. Patients
      with high glucose levels were divided into three SIH groups with diabetes
      mellitus (DM), based on the following definitions: (1) same glycemic gap from
      ADAG; (2) same percentage of elevated glucose of ADAG, from which percentage
      could also be reflected by the stress hyperglycemia ratio (SHR), calculated as
      the admission glucose level divided by ADAG; or (3) same percentage of elevated
      glucose as patients with a defined SIH level, in trauma patients with and without
      diabetes. Patients with incomplete registered data were excluded. The primary
      hypothesis of this study was that SIH in patients with diabetes would present
      worse mortality outcomes than in those without. Detailed data of SIH in patients
      with diabetes were retrieved from the Trauma Registry System. Results: Among the
      546 patients with DH, 332 (32.0%), 188 (18.1%), and 106 (10.2%) were assigned as
      diabetes patients with SIH, based on defined glucose levels, set at 250 mg/dL,
      300 mg/dL, and 350 mg/dL, respectively. In patients with defined cut-off glucose
      levels of 250 mg/dL and 300 mg/dL, SIH was associated with a 3.5-fold (95%
      confidence interval (CI) 1.61-7.46; p = 0.001) and 3-fold (95% CI 1.11-8.03; p =
      0.030) higher odds of mortality, adjusted by sex, age, pre-existing
      comorbidities, and injury severity score, than the 491 patients with diabetic
      normoglycemia (DN). However, in patients with a defined cut-off glucose level of
      350 mg/dL, adjusted mortality in SIH in DM was insignificantly different than
      that in DM. According to the receiver operating characteristic (ROC) curve
      analysis, a blood sugar of 233 mg/dL, a glycemic gap of 79 (i.e., blood sugar of
      251 mg/dL), and a SHR of 1.45 (i.e., blood sugar of 250 mg/dL) were identified as
      cut-offs for mortality outcomes, with AUCs of 0.622, 0.653, and 0.658,
      respectively. Conclusions: In this study, a cut-off glucose level of 250 mg/dL
      was selected to provide a better definition of SIH in DM than glucose levels of
      300 mg/dL or 350 mg/dL.

PMID- 29215582
TI  - Recent Enhancements to Interline and Electron Multiplying CCD Image Sensors.
AB  - This paper describes recent process modifications made to enhance the performance
      of interline and electron-multiplying charge-coupled-device (EMCCD) image
      sensors. By use of MeV ion implantation, quantum efficiency in the NIR region of
      the spectrum was increased by 2*, and image smear was reduced by 6 dB. By
      reducing the depth of the shallow photodiode (PD) implants, the photodiode-to
      vertical-charge-coupled-device (VCCD) transfer gate voltage required for no-lag
      operation was reduced by 3 V, and the electronic shutter voltage was reduced by 9
      V. The thinner, surface pinning layer also resulted in a reduction of smear by 4
      dB in the blue portion of the visible spectrum. For EMCCDs, gain aging was
      eliminated by providing an oxide-only dielectric under its multiplication phase,
      while retaining the oxide-nitride-oxide (ONO) gate dielectrics elsewhere in the
      device.

PMID- 29215583
TI  - Response to Comments on Zheng et al. "Association between Promoter Methylation of
      Gene ERCC3 and Benzene Hematotoxicity" Int. J. Environ. Res. Public Health 2017,
      14, 1393.
AB  - We would like to thank Moshammer and Poteser for their comments [...].

PMID- 29215584
TI  - A Positive Control for Detection of Functional CD4 T Cells in PBMC: The CPI Pool.
AB  - Testing of peripheral blood mononuclear cells (PBMC) for immune monitoring
      purposes requires verification of their functionality. This is of particular
      concern when the PBMC have been shipped or stored for prolonged periods of time.
      While the CEF (Cytomegalo-, Epstein-Barr and Flu-virus) peptide pool has become
      the gold standard for testing CD8 cell functionality, a positive control for CD4
      cells is so far lacking. The latter ideally consists of proteins so as to control
      for the functionality of the antigen processing and presentation compartments, as
      well. Aiming to generate a positive control for CD4 cells, we first selected 12
      protein antigens from infectious/environmental organisms that are ubiquitous:
      Varicella, Influenza, Parainfluenza, Mumps, Cytomegalovirus, Streptococcus,
      Mycoplasma, Lactobacillus, Neisseria, Candida, Rubella, and Measles. Of these
      antigens, three were found to elicited interferon (IFN)-gamma-producing CD4 cells
      in the majority of human test subjects: inactivated cytomegalo-, parainfluenza-,
      and influenza virions (CPI). While individually none of these three antigens
      triggered a recall response in all donors, the pool of the three (the 'CPI
      pool'), did. One hundred percent of 245 human donors tested were found to be CPI
      positive, including Caucasians, Asians, and African-Americans. Therefore, the CPI
      pool appears to be suitable to serve as universal positive control for verifying
      the functionality of CD4 and of antigen presenting cells.

PMID- 29215585
TI  - Xanthones and Quinolones Derivatives Produced by the Deep-Sea-Derived Fungus
      Penicillium sp. SCSIO Ind16F01.
AB  - Chemical investigation of the fungus Penicillium sp. SCSIO Ind16F01 derived from
      deep-sea sediment sample afforded a new xanthone, 3,8-dihydroxy-2-methyl-9
      oxoxanthene-4-carboxylic acid methyl ester (1) and a new chromone, coniochaetone
      J (2), together with three known xanthones, 8-hydroxy-6-methyl-9-oxo-9H-xanthene
      1-carboxylic acid methyl ester (3), 7,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1
      carboxylic acid methyl ester (4), 1,6,8-trihydroxy-3-(hydroxymethyl)anthraquinone
      (5), three known chromones, coniochaetone B (6), citrinolactones B (7),
      epiremisporine B (8), and four reported rare class of N-methyl quinolone lactams:
      quinolactacins B (9), C1 (10), and C2 (11), and quinolonimide (12). The
      structures of new compounds were determined by analysis of the NMR and MS
      spectroscopic data. Those isolated compounds were evaluated for their antiviral
      (EV71 and H3N2) and cytotoxic activities.

PMID- 29215586
TI  - Investigation of Polyamine Metabolism and Homeostasis in Pancreatic Cancers.
AB  - Pancreatic cancers are currently the fourth leading cause of cancer-related death
      and new therapies are desperately needed. The most common pancreatic cancer is
      pancreatic ductal adenocarcinoma (PDAC). This report describes the development of
      therapies, which effectively deplete PDAC cells of their required polyamine
      growth factors. Of all human tissues, the pancreas has the highest level of the
      native polyamine spermidine. To sustain their high growth rates, PDACs have
      altered polyamine metabolism, which is reflected in their high intracellular
      polyamine levels and their upregulated import of exogenous polyamines. To
      understand how these cancers respond to interventions that target their specific
      polyamine pools, L3.6pl human pancreatic cancer cells were challenged with
      specific inhibitors of polyamine biosynthesis. We found that pancreatic cell
      lines have excess polyamine pools, which they rebalance to address deficiencies
      induced by inhibitors of specific steps in polyamine biosynthesis (e.g.,
      ornithine decarboxylase (ODC), spermidine synthase (SRM), and spermine synthase
      (SMS)). We also discovered that combination therapies targeting ODC, SMS, and
      polyamine import were the most effective in reducing intracellular polyamine
      pools and reducing PDAC cell growth. A combination therapy containing
      difluoromethylornithine (DFMO, an ODC inhibitor) and a polyamine transport
      inhibitor (PTI) were shown to significantly deplete intracellular polyamine
      pools. The additional presence of an SMS inhibitor as low as 100 nM was
      sufficient to further potentiate the DFMO + PTI treatment.

PMID- 29215587
TI  - Cyclic Behavior of Low Rise Concrete Shear Walls Containing Recycled Coarse and
      Fine Aggregates.
AB  - In this study, the cyclic behaviors of low rise concrete shear walls using
      recycled coarse or fine aggregates were investigated. Eight low rise Recycled
      Aggregates Concrete (RAC) shear wall specimens were designed and tested under a
      cyclic loading. The following parameters were varied: replacement percentages of
      recycled coarse or fine aggregates, reinforcement ratio, axial force ratio and X
      shaped rebars brace. The failure characteristics, hysteretic behavior, strength
      and deformation capacity, strain characteristics and stiffness were studied. Test
      results showed that the using of the Recycled Coarse Aggregates (RCA) and its
      replacement ratio had almost no influence on the mechanical behavior of the shear
      wall; however, the using of Recycled Fine Aggregates (RFA) had a certain
      influence on the ductility of the shear wall. When the reinforcement ratio
      increased, the strength and ductility also increased. By increasing the axial
      force ratio, the strength increased but the ductility decreased significantly.
      The encased brace had a significant effect on enhancing the RAC shear walls. The
      experimental maximum strengths were evaluated with existing design codes, it was
      indicated that the strength evaluation of the low rise RAC shear walls can follow
      the existing design codes of the conventional concrete shear walls.

PMID- 29215588
TI  - Cutting Edge Methods for Non-Invasive Disease Diagnosis Using E-Tongue and E-Nose
      Devices.
AB  - Biomimetic cross-reactive sensor arrays (B-CRSAs) have been used to detect and
      diagnose a wide variety of diseases including metabolic disorders, mental health
      diseases, and cancer by analyzing both vapor and liquid patient samples.
      Technological advancements over the past decade have made these systems
      selective, sensitive, and affordable. To date, devices for non-invasive and
      accurate disease diagnosis have seen rapid improvement, suggesting a feasible
      alternative to current standards for medical diagnostics. This review provides an
      overview of the most recent B-CRSAs for diagnostics (also referred to electronic
      noses and tongues in the literature) and an outlook for future technological
      development.

PMID- 29215589
TI  - Impact of Omega-3 Fatty Acids on the Gut Microbiota.
AB  - Long-term dietary habits play a crucial role in creating a host-specific gut
      microbiota community in humans. Despite the many publications about the effects
      of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3
      polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined.
      The few studies completed in adults showed some common changes in the gut
      microbiota after omega-3 PUFA supplementation. In particular, a decrease in
      Faecalibacterium, often associated with an increase in the Bacteroidetes and
      butyrate-producing bacteria belonging to the Lachnospiraceae family, has been
      observed. Coincidentally, a dysbiosis of these taxa is found in patients with
      inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by
      reverting the microbiota composition in these diseases, and increase the
      production of anti-inflammatory compounds, like short-chain fatty acids. In
      addition, accumulating evidence in animal model studies indicates that the
      interplay between gut microbiota, omega-3 fatty acids, and immunity helps to
      maintain the intestinal wall integrity and interacts with host immune cells.
      Finally, human and animal studies have highlighted the ability of omega-3 PUFAs
      to influence the gut-brain axis, acting through gut microbiota composition. From
      these findings, the importance of the omega-3 connection to the microbiota
      emerges, encouraging further studies.

PMID- 29215591
TI  - Self-Coexistence among IEEE 802.22 Networks: Distributed Allocation of Power and
      Channel.
AB  - Ensuring self-coexistence among IEEE 802.22 networks is a challenging problem
      owing to opportunistic access of incumbent-free radio resources by users in co
      located networks. In this study, we propose a fully-distributed non-cooperative
      approach to ensure self-coexistence in downlink channels of IEEE 802.22 networks.
      We formulate the self-coexistence problem as a mixed-integer non-linear
      optimization problem for maximizing the network data rate, which is an NP-hard
      one. This work explores a sub-optimal solution by dividing the optimization
      problem into downlink channel allocation and power assignment sub-problems.
      Considering fairness, quality of service and minimum interference for customer
      premises-equipment, we also develop a greedy algorithm for channel allocation and
      a non-cooperative game-theoretic framework for near-optimal power allocation. The
      base stations of networks are treated as players in a game, where they try to
      increase spectrum utilization by controlling power and reaching a Nash
      equilibrium point. We further develop a utility function for the game to increase
      the data rate by minimizing the transmission power and, subsequently, the
      interference from neighboring networks. A theoretical proof of the uniqueness and
      existence of the Nash equilibrium has been presented. Performance improvements in
      terms of data-rate with a degree of fairness compared to a cooperative branch-and
      bound-based algorithm and a non-cooperative greedy approach have been shown
      through simulation studies.

PMID- 29215590
TI  - Joint Effects of PON1 Polymorphisms and Vegetable Intake on Ischemic Stroke: A
      Family-Based Case Control Study.
AB  - Paraoxonase 1 gene (PON1) polymorphisms and dietary vegetable and fruit intake
      are both established determinants of ischemic stroke (IS). However, little is
      known about whether these factors jointly influence the risk of IS. We analyzed
      the main effects of PON1, as well as the interactions between PON1 and dietary
      vegetable or fruit intake with the risk of total IS and its subtypes in a family
      based case-control study conducted among 2158 Chinese participants (1007 IS cases
      and 1151 IS-free controls) from 918 families. Conditional logistic regression
      models, with each family as a stratum, were used to examine the association
      between rs662 and IS. Gene-diet interactions were tested by including a cross
      product term of dietary vegetable or fruit intake by rs662_G allele count in the
      models. Each copy of the PON1 rs662_G allele was associated with 28% higher risk
      of total IS (p = 0.008) and 32% higher risk of large artery atherosclerosis
      subtype (LAA) (p = 0.01). We observed an interaction between rs662 and vegetable
      intake for both total IS (p = 0.006) and LAA (p = 0.02) after adjustment for
      covariates. Individuals who carry the rs662_A allele may benefit to a greater
      extent from intake of vegetables and thus be more effectively protected from
      ischemic stroke, whereas carriers of the G allele may still remain at greater
      risk for ischemic stroke due to their genetic backgrounds even when they consume
      a high level of vegetables. More studies are needed to replicate our findings
      among other populations.

PMID- 29215593
TI  - Risk Factors Associated with Brucella Seropositivity in Sheep and Goats in Duhok
      Province, Iraq.
AB  - Sera from 432 small ruminants (335 sheep and 97 goats) from 72 farms in Duhok
      Province, northern Iraq, were collected to investigate risk factors associated
      with brucellosis seropositivity. Serum samples were tested using the Rose Bengal
      test (RBT) and an indirect enzyme-linked immunosorbent assay (iELISA). Using
      parallel interpretation, RBT and iELISA results showed that 31.7% (95% confidence
      interval (CI): 26.1, 36.3) of sheep and 34.0% (95% CI: 24.7, 44.3) of goats had
      antibodies against Brucella in the study area. A random-effects multivariable
      logistic regression model indicated that a higher chance of being seropositive
      (odds ratio (OR) = 1.7; 95% 1.4; 2.2) was associated with an increase in the age
      of animals. The odds of Brucella seropositivity in flocks where sheep and goats
      grazed together was 2.0 times higher (95% CI: 1.08; 3.9) compared to flocks where
      sheep and goats grazed separately. The odds of Brucella seropositivity in small
      ruminants was 2.2 higher (95% CI: 1.2; 4.3) for animals originating from farms
      with a history of goat abortion in the preceding 12 months. In contrast, for
      every 1000 Iraqi Dinars (~0.85 US Dollar) spent by the farmers on control of
      Brucella in their flocks, the odds of Brucella seropositivity decreased
      significantly (OR = 0.9, p-value = 0.021). The final model also indicated
      significant differences in Brucella seropositivity between the different
      districts of Duhok Province. This study provides a contribution to the
      epidemiology of brucellosis in small ruminants in northern Iraq.

PMID- 29215592
TI  - Natural Korean Medicine Dang-Gui: Biosynthesis, Effective Extraction and
      Formulations of Major Active Pyranocoumarins, Their Molecular Action Mechanism in
      Cancer, and Other Biological Activities.
AB  - Angelica gigas Nakai (AGN) is a crucial oriental medicinal herb that grows
      especially in Korea and the Far-East countries. It contains chemically active
      compounds like pyranocoumarins, polyacetylenes and essential oils, which might be
      useful for treatment of several chronic diseases. It has been used for centuries
      as a traditional medicine in Southeast Asia, but in Western countries is used as
      a functional food and a major ingredient of several herbal products. The genus
      Angelica is also known as 'female ginseng' due to its critical therapeutic role
      in female afflictions, such as gynecological problems. However, it is well
      documented that the AGN pyranocoumarins may play vital beneficial roles against
      cancer, neurodisorders, inflammation, osteoporosis, amnesia, allergies,
      depression, fungi, diabetes, ischemia, dermatitis, reactive oxygen species (ROS)
      and androgen. Though numerous studies revealed the role of AGN pyranocoumarins as
      therapeutic agents, none of the reviews have published their molecular mechanism
      of action. To the best of our knowledge, this would be the first review that aims
      to appraise the biosynthesis of AGN's major active pyranocoumarins, discuss
      effective extraction and formulation methods, and detail the molecular action
      mechanism of decursin (D), decursinol angelate (DA) and decursinol (DOH) in
      chronic diseases, which would further help extension of research in this area.

PMID- 29215594
TI  - Facile Determination of Sodium Ion and Osmolarity in Artificial Tears by
      Sequential DNAzymes.
AB  - Despite high relevance of tear osmolarity and eye abnormality, numerous methods
      for detecting tear osmolarity rely upon expensive osmometers. We report a
      reliable method for simply determining sodium ion-based osmolarity in artificial
      tears using sequential DNAzymes. When sodium ion-specific DNAzyme and peroxidase
      like DNAzyme were used as a sensing and detecting probe, respectively, the
      concentration of Na+ in artificial tears could be measured by absorbance or
      fluorescence intensity, which was highly correlated with osmolarity over the
      diagnostic range (R2 > 0.98). Our approach is useful for studying eye diseases in
      relation to osmolarity.

PMID- 29215595
TI  - The Role of Vitamin D in Non-Scarring Alopecia.
AB  - Non-scarring hair loss is a common problem that affects both male and female
      patients. Since any disturbances in the hair follicle cycle may lead to hair
      shedding, or alopecia, it is not surprising that the possible role of vitamin D
      in alopecia was investigated in many studies. Vitamin D has been shown to have
      many important functions. A growing body of evidence shows that vitamin D and its
      receptor are responsible for maintaining not only calcium homeostasis but also
      skin homeostasis. Moreover, vitamin D could also regulate cutaneous innate and
      adaptive immunity. This paper presents a review of current literature considering
      the role of vitamin D in alopecia areata, telogen effluvium, and female pattern
      hair loss. The majority of studies revealed decreased serum 25-hydroxyvitamin D
      levels in patients with different types of non-scarring alopecia, which could
      suggest its potential role in the pathogenesis of hair loss. According to the
      authors, vitamin D supplementation could be a therapeutic option for patients
      with alopecia areata, female pattern hair loss, or telogen effluvium. However,
      further studies on a larger group of patients are required.

PMID- 29215596
TI  - RSV Infection in Human Macrophages Promotes CXCL10/IP-10 Expression during
      Bacterial Co-Infection.
AB  - Respiratory syncytial virus (RSV), a major etiologic agent of acute lower
      respiratory infection constitutes the most important cause of death in young
      children worldwide. Viral/bacterial mixed infections are related to severity of
      respiratory inflammatory diseases, but the underlying mechanisms remain poorly
      understood. We have previously investigated the intracellular mechanisms that
      mediate the immune response in the context of influenza virus/Streptococcus
      pneumoniae (Sp) co-infection using a model of human monocyte-derived macrophages
      (MDMs). Here, we set up and characterized a similar model of MDMs to investigate
      different scenarios of RSV infection and co-infection with Sp. Our results
      suggest that Sp contributes to a faster and possibly higher level of CXCL10/IP-10
      expression induced by RSV infection in human MDMs.

PMID- 29215597
TI  - Application of Pharmacokinetics Modelling to Predict Human Exposure of a Cationic
      Liposomal Subunit Antigen Vaccine System.
AB  - The pharmacokinetics of a liposomal subunit antigen vaccine system composed of
      the cationic lipid dimethyldioctadecylammonium bromide (DDA) and the
      immunostimulatory agent trehalose 6,6-dibehenate (TDB) (8:1 molar ratio) combined
      with the Ag85B-ESAT-6 (H1) antigen were modelled using mouse in-vivo data.
      Compartment modelling and physiologically based pharmacokinetics (PBPK) were used
      to predict the administration site (muscle) and target site (lymph) temporal
      concentration profiles and factors governing these. Initial estimates using
      compartmental modelling established that quadriceps pharmacokinetics for the
      liposome demonstrated a long half-life (22.6 days) compared to the associated
      antigen (2.62 days). A mouse minimal-PBPK model was developed and successfully
      predicted quadriceps liposome and antigen pharmacokinetics. Predictions for the
      popliteal lymph node (PLN) aligned well at earlier time-points. A local
      sensitivity analysis highlighted that the predicted AUCmuscle was sensitive to
      the antigen degradation constant kdeg (resulting in a 3-log change) more so than
      the fraction escaping the quadriceps (fe) (resulting in a 10-fold change), and
      the predicted AUCPLN was highly sensitive to fe. A global sensitivity analysis of
      the antigen in the muscle demonstrated that model predictions were within the
      50th percentile for predictions and showed acceptable fits. To further translate
      in-vitro data previously generated by our group, the mouse minimal-PBPK model was
      extrapolated to humans and predictions made for antigen pharmacokinetics in
      muscle and PLN. Global analysis demonstrated that both kdeg and fe had a minimal
      impact on the resulting simulations in the muscle but a greater impact in the
      PLN. In summary, this study has predicted the in-vivo fate of DDA:TDB:H1 in
      humans and demonstrated the roles that formulation degradation and fraction
      escaping the depot site can play upon the overall depot effect within the site of
      administration.

PMID- 29215598
TI  - Li-Decorated beta12-Borophene as Potential Candidates for Hydrogen Storage: A
      First-Principle Study.
AB  - The hydrogen storage properties of pristine beta12-borophene and Li-decorated
      beta12-borophene are systemically investigated by means of first-principles
      calculations based on density functional theory. The adsorption sites, adsorption
      energies, electronic structures, and hydrogen storage performance of pristine
      beta12-borophene/H2 and Li-beta12-borophene/H2 systems are discussed in detail.
      The results show that H2 is dissociated into Two H atoms that are then
      chemisorbed on beta12-borophene via strong covalent bonds. Then, we use Li atom
      to improve the hydrogen storage performance and modify the hydrogen storage
      capacity of beta12-borophene. Our numerical calculation shows that Li-beta12
      borophene system can adsorb up to 7 H2 molecules; while 2Li-beta12-borophene
      system can adsorb up to 14 H2 molecules and the hydrogen storage capacity up to
      10.85 wt %.

PMID- 29215599
TI  - Systematic Analysis of Transcriptomic Profile of Renal Cell Carcinoma under Long
      Term Hypoxia Using Next-Generation Sequencing and Bioinformatics.
AB  - Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with
      both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia
      inducible factor-dependent signaling. In this study, we investigated the effects
      of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to
      identify potential genes and microRNAs associated with tumor malignancy. The
      transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term
      hypoxia were analyzed using next-generation sequencing. The results showed that
      long-term hypoxia promoted the ability of colony formation and transwell
      migration compared to normoxia. In addition, the differentially expressed genes
      induced by long-term hypoxia were involved in various biological processes
      including cell proliferation, the tumor necrosis factor signaling pathway, basal
      cell carcinoma and cancer pathways. The upregulated (L1CAM and FBN1) and
      downregulated (AUTS2, MAPT, AGT and USH1C) genes in 786-O under long-term hypoxia
      were also observed in clinical ccRCC samples along with malignant grade. The
      expressions of these genes were significantly correlated with survival outcomes
      in patients with renal cancer. We also found that long-term hypoxia in 786-O
      resulted in decreased expressions of hsa-mir-100 and hsa-mir-378 and this effect
      was also observed in samples of metastatic ccRCC compared to samples of non
      metastatic ccRCC. These findings may provide a new direction for the study of
      potential molecular mechanisms associated with the progression of ccRCC.

PMID- 29215601
TI  - Analysis of the Comprehensive Tensile Relationship in Electrospun Silk
      Fibroin/Polycaprolactone Nanofiber Membranes.
AB  - The mechanical properties of electrospun nanofiber membranes are critical for
      their applications. A clear understanding of the mechanical properties that
      result from the characteristics of the individual fiber and membrane
      microstructure is vital in the design of fiber composites. In this reported
      study, silk fibroin (SF)/polycaprolactone (PCL) composite nanofiber membranes
      were preparedusing an electrostatic spinning technology. The nanofiber
      orientation distribution (FOD) of the membrane was analyzed using multi-layer
      image fusion technology, and the results indicated the presence of an
      approximately uniform distribution of fibers in the electrospun membranes. The
      relationship between the single nanofiber and the membrane was established by
      analyzing the geometrical structure of the cell by employing a representative
      volume element (RVE) analysis method. The mechanical properties of the 272 nm
      diameter SF/PCL composite fibers were then predicted using the developed model.

PMID- 29215600
TI  - Three-Dimensional Shape Measurements of Specular Objects Using Phase-Measuring
      Deflectometry.
AB  - The fast development in the fields of integrated circuits, photovoltaics, the
      automobile industry, advanced manufacturing, and astronomy have led to the
      importance and necessity of quickly and accurately obtaining three-dimensional
      (3D) shape data of specular surfaces for quality control and function evaluation.
      Owing to the advantages of a large dynamic range, non-contact operation, full
      field and fast acquisition, high accuracy, and automatic data processing, phase
      measuring deflectometry (PMD, also called fringe reflection profilometry) has
      been widely studied and applied in many fields. Phase information coded in the
      reflected fringe patterns relates to the local slope and height of the measured
      specular objects. The 3D shape is obtained by integrating the local gradient data
      or directly calculating the depth data from the phase information. We present a
      review of the relevant techniques regarding classical PMD. The improved PMD
      technique is then used to measure specular objects having discontinuous and/or
      isolated surfaces. Some influential factors on the measured results are
      presented. The challenges and future research directions are discussed to further
      advance PMD techniques. Finally, the application fields of PMD are briefly
      introduced.

PMID- 29215602
TI  - Proteomic Contributions to Medicinal Plant Research: From Plant Metabolism to
      Pharmacological Action.
AB  - Herbal medicine is a clinical practice of utilizing medicinal plant derivatives
      for therapeutic purposes. It has an enduring history worldwide and plays a
      significant role in the fight against various diseases. Herbal drug combinations
      often exhibit synergistic therapeutic action compared with single-constituent
      dosage, and can also enhance the cytotoxicity induced by chemotherapeutic drugs.
      To explore the mechanism underlying the pharmacological action of herbs,
      proteomic approaches have been applied to the physiology of medicinal plants and
      its effects on animals. This review article focuses on the existing proteomics
      based medicinal plant research and discusses the following topics: (i) plant
      metabolic pathways that synthesize an array of bioactive compounds; (ii)
      pharmacological action of plants tested using in vivo and in vitro studies; and
      (iii) the application of proteomic approaches to indigenous plants with scarce
      sequence information. The accumulation of proteomic information in a biological
      or medicinal context may help in formulating the effective use of medicinal
      plants.

PMID- 29215603
TI  - Differential Location and Distribution of Hepatic Immune Cells.
AB  - The liver is one of the main organs in the body, performing several metabolic and
      immunological functions that are indispensable to the organism. The liver is
      strategically positioned in the abdominal cavity between the intestine and the
      systemic circulation. Due to its location, the liver is continually exposed to
      nutritional insults, microbiota products from the intestinal tract, and to toxic
      substances. Hepatocytes are the major functional constituents of the hepatic
      lobes, and perform most of the liver's secretory and synthesizing functions,
      although another important cell population sustains the vitality of the organ:
      the hepatic immune cells. Liver immune cells play a fundamental role in host
      immune responses and exquisite mechanisms are necessary to govern the density and
      the location of the different hepatic leukocytes. Here we discuss the location of
      these pivotal cells within the different liver compartments, and how their
      frequency and tissular location can dictate the fate of liver immune responses.

PMID- 29215604
TI  - Dietary Factors and Female Breast Cancer Risk: A Prospective Cohort Study.
AB  - Breast cancer is the leading cause of cancer in females and has become a major
      global health priority. This prospective cohort study investigated the
      association of dietary factors, including food items and dietary habits, with the
      risk of breast cancer in Korean women. Study participants were women aged 30
      years or older, recruited from the National Cancer Center in South Korea between
      August 2002 and May 2007. They were followed until December 2014 using the Korea
      Central Cancer Registry to identify breast cancer cases. Among 5046 non-pre
      diagnosed cancer participants, 72 breast cancer cases were prospectively
      identified. Participants with breast cancer had a significantly higher
      educational level (college or higher: 58.3% vs. 39.5%, p = 0.01), were more
      likely to have ever smoked (22.2% vs. 7.8%, p < 0.001), and were more likely to
      have a history of benign breast tumors (10% vs. 4%, p = 0.02) than non-cases.
      Consumption of grilled meat conferred a significantly higher risk of breast
      cancer in all women (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.09
      2.85) and in postmenopausal women (HR 3.06, 95% CI 1.31-7.15). High-cholesterol
      food intake was associated with a higher risk in all women (HR 1.69, 95% CI 1.01
      2.82). Irregular meal intake was associated with an elevated risk in all women
      (HR 2.19, 95% CI 1.20-3.98, p for trend = 0.01) and in premenopausal women (HR
      2.35, 95% CI 1.13-4.91, p for trend = 0.03). Our findings suggest that grilled
      meat and high-cholesterol food intake and irregular eating habits may be
      associated with a higher risk of breast cancer. Further studies with longer
      follow-up periods that include information on portion size, hormone receptor
      status, carcinogen levels in grilled meat, and a classification of foods by
      source are required.

PMID- 29215605
TI  - Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery.
AB  - Marine drugs have developed rapidly in recent decades. Cone snails, a group of
      more than 700 species, have always been one of the focuses for new drug
      discovery. These venomous snails capture prey using a diverse array of unique
      bioactive neurotoxins, usually named as conotoxins or conopeptides. These
      conotoxins have proven to be valuable pharmacological probes and potential drugs
      due to their high specificity and affinity to ion channels, receptors, and
      transporters in the nervous systems of target prey and humans. Several research
      groups, including ours, have examined the venom gland of cone snails using a
      combination of transcriptomic and proteomic sequencing, and revealed the
      existence of hundreds of conotoxin transcripts and thousands of conopeptides in
      each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins
      have been published, and the number is still increasing quickly. However, more
      than 98% of these sequences still lack 3D structural and functional information.
      With the rapid development of genomics and bioinformatics in recent years,
      functional predictions and investigations on conotoxins are making great progress
      in promoting the discovery of novel drugs. For example, omega-MVIIA was approved
      by the U.S. Food and Drug Administration in 2004 to treat chronic pain, and nine
      more conotoxins are at various stages of preclinical or clinical evaluation. In
      short, the genus Conus, the big family of cone snails, has become an important
      genetic resource for conotoxin identification and drug development.

PMID- 29215606
TI  - Cognitive and Mood Effects of a Nutrient Enriched Breakfast Bar in Healthy
      Adults: A Randomised, Double-Blind, Placebo-Controlled, Parallel Groups Study.
AB  - OBJECTIVES: Few previous studies have assessed the effects of concomitant
      administration of multiple potentially psychoactive nutrients. METHODS: 95
      healthy adult participants consumed either a nutrient enriched breakfast bar
      (containing alpha-Linolenic acid, l-tyrosine, l-theanine, vitamins, minerals and
      21.5 mg of caffeine) or an isocaloric, macronutrient matched control bar for 56
      days. Cognitive function and mood were assessed pre-dose and at 40- and 160-min
      post-dose on the 1st and 56th day of the intervention period. RESULTS: The
      results demonstrated acute effects of treatment across post-dose assessments on
      both assessment days in terms of alertness, and on tasks assessing attention,
      working and episodic memory and executive function, including cognitively
      demanding Serial subtraction and Rapid Visual Information Processing tasks. There
      were no evident chronic effects independent of the breakfast bars' acute effects.
      DISCUSSION: These results demonstrate that a nutrient enriched breakfast bar with
      low caffeine content can exert striking beneficial effects on acute cognitive
      function and alertness.

PMID- 29215609
TI  - Questioning the Utility of Breath Testing in Clinical Practice.

PMID- 29215607
TI  - Proteomic and functional analysis identifies galectin-1 as a novel regulatory
      component of the cytotoxic granule machinery.
AB  - Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful
      weapons against intracellular microbes and tumor cells. Despite significant
      progress, there is still limited information on the molecular mechanisms
      implicated in target-driven degranulation, effector cell survival and composition
      and structure of the lytic granules. Here, using a proteomic approach we
      identified a panel of putative cytotoxic granule proteins, including some already
      known granule constituents and novel proteins that contribute to regulate the CTL
      lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous
      immune regulatory lectin, as an integral component of the secretory granule
      machinery and unveil the unexpected function of this lectin in regulating CTL
      killing activity. Mechanistic studies revealed the ability of Gal1 to control the
      non-secretory lytic pathway by influencing Fas-Fas ligand interactions. This
      study offers new insights on the composition of the cytotoxic granule machinery,
      highlighting the dynamic cross talk between secretory and non-secretory pathways
      in controlling CTL lytic function.

PMID- 29215610
TI  - Breath Testing Consensus Guidelines for SIBO: RES IPSA LOCQUITOR.

PMID- 29215608
TI  - H19 lncRNA alters methylation and expression of Hnf4alpha in the liver of
      metformin-exposed fetuses.
AB  - Metformin is the most widely used anti-diabetic medication worldwide. However,
      human and animal studies suggest that prenatal metformin exposure may increase
      the risk of metabolic disorders in adult offspring, yet the underpinning
      mechanism remains unclear. Here we report that metformin-exposed mouse fetuses
      exhibit elevated expression of the H19 long noncoding RNA, which induces
      hypomethylation and increased expression of hepatocyte nuclear factor 4alpha
      (HNF4alpha). As a transcription factor essential for morphological and functional
      differentiation of hepatocytes, HNF4alpha also has an indispensable role in the
      regulation of expression of gluconeogenic genes. Consistently, H19 overexpression
      in a human liver cell line leads to decreased methylation and increased
      expression of Hnf4alpha, with concomitant activation of the gluconeogenic
      program. Mechanistically, we show that the methylation change of Hnf4alpha is
      induced by H19-mediated regulation of S-adenosylhomocysteine hydrolase. We also
      provide evidence that altered H19 expression is a direct effect of metformin in
      the fetal liver. Our results suggest that metformin from the mother can directly
      act upon the fetal liver to modify Hnf4alpha expression, a key factor for both
      liver development and function, and that perturbation of this H19/Hnf4alpha
      mediated pathway may contribute to the fetal origin of adult metabolic
      abnormalities.

PMID- 29215611
TI  - Parietal Cell Protrusions and Dilated Oxyntic Glands from Use of Vonoprazan.

PMID- 29215612
TI  - Endoscopic Gastrojejunostomy: A Novel NOTES Technique.

PMID- 29215613
TI  - Continuing Medical Education: December 2017.

PMID- 29215615
TI  - Conflicts of Interest in the North American Consensus on Breath Testing.

PMID- 29215616
TI  - Response to Tuck et al.

PMID- 29215617
TI  - Preserved Liver Transplant After PD-1 Pathway Inhibitor for Hepatocellular
      Carcinoma.

PMID- 29215618
TI  - Is Double-Dose Esomeprazole With Bismuth Really Safe?

PMID- 29215619
TI  - Endoscopic Placement of a U-Shaped Plastic Stent in Patients With Recurrent Acute
      Pancreatitis and Incomplete Pancreas Divisum.

PMID- 29215620
TI  - Familial High-Serum Gamma-Glutamyltransferase Activity.

PMID- 29215621
TI  - Continuing Medical Education: December 2017.

PMID- 29215622
TI  - Novel PRSS1 Mutation p.P17T Validates Pathogenic Relevance of CTRC-Mediated
      Processing of the Trypsinogen Activation Peptide in Chronic Pancreatitis.

PMID- 29215623
TI  - Response to Paterson et al.

PMID- 29215624
TI  - Obstructive Jaundice Caused by Heterotopic Pancreas.

PMID- 29215625
TI  - Response to Reinink.

PMID- 29215626
TI  - Continuing Medical Education Questions: December 2017: Isolated anti-HBc: The
      Relevance of Hepatitis B Core Antibody-A Review of New Issues.

PMID- 29215627
TI  - A Pharmacokinetic Rationale for Proactive Therapeutic Drug Monitoring of Anti-TNF
      Drugs.

PMID- 29215628
TI  - Response to Maltz.

PMID- 29215629
TI  - Proton Pump Inhibitors and Dementia: Deciphering the Data.
AB  - Proton pump inhibitors (PPIs) are effective and suppressing acid, and therefore
      have efficacy against gastric acid-related disorders. The long-term safety of
      PPIs is less clear and there have been a number of studies raising concerns
      regarding risk of pneumonia, fracture, Clostridium difficile, chronic renal
      failure, and dementia. This latter concern is addressed by a study in this issue
      of AJG using health care registry data and found there was no association between
      PPI use and Alzheimer's dementia. Furthermore, there was no increased risk of
      dementia with long-term use of PPIs or higher doses of PPIs. Discrepancies
      between studies probably relate to multiple testing and residual confounding and
      currently there is insufficient evidence to suggest that the association between
      PPIs and dementia is causal.

PMID- 29215630
TI  - Continuing Medical Education Questions: December 2017: Risk of Clostridium
      difficile Infection in Patients With Celiac Disease: A Population-Based Study.

PMID- 29215631
TI  - Which Patients with Mild Acute Pancreatitis Require Prolonged Hospitalization?
AB  - OBJECTIVES: In our experience, a subset of mild acute pancreatitis (AP) patients,
      as defined by the Revised Atlanta Classification, has longer than expected
      hospitalization. Our aims are to report the prevalence of patients with mild AP
      who have a prolonged length of stay (LOS), evaluate the etiology, thoroughly
      phenotype, and finally compare this subset to those with expected LOS. METHODS:
      Patients admitted with AP from 2003 to 2015 were prospectively enrolled into this
      cohort study. LOS >=8 days was considered as prolonged LOS. Data on demographics,
      clinical and laboratory variables, management, and outcomes was both
      prospectively and retrospectively collected. Continuous variables were compared
      using the nonparametric t-test (Wilcoxon's test) and categorical variables using
      the Pearson's chi2 test. RESULTS: Among 231 enrolled mild AP patients, 46 (20%)
      had a prolonged LOS (>=8 days). The main determinants of prolonged LOS included
      ongoing pancreatitis-related symptoms (n=31, 67.4%) and performance of
      cholecystectomy (n=11, 23.9%). When compared to patients with expected LOS (<8
      days, n=185), patients with prolonged LOS due to ongoing symptoms (n=31) were
      more likely to have systemic inflammatory response syndrome at 48 h from
      admission (37% vs. 13.4%, P<0.001), a prolonged fasting period (6.6 vs. 2.8 days,
      P<0.001), and need for nutritional support (30% vs. 1.6%, P<0.001). CONCLUSIONS:
      About 20% of patients with mild AP have a longer than expected hospital stay,
      mostly attributed to ongoing pancreatitis-related symptoms. An early decision (at
      72 h) for enteral nutrition support in these patients needs to be explored so as
      to shorten hospitalization and reduce cost of care.

PMID- 29215632
TI  - Assembly of phospholipid nanodiscs of controlled size for structural studies of
      membrane proteins by NMR.
AB  - Suitable membrane mimetics are crucial to the performance of structural and
      functional studies of membrane proteins. Phospholipid nanodiscs (formed when a
      membrane scaffold protein encircles a small portion of a lipid bilayer) have
      native-like membrane properties. These have been used for a variety of functional
      studies, but structural studies by high-resolution solution-state NMR
      spectroscopy of membrane proteins in commonly used nanodiscs of 10-nm diameter
      were limited by the high molecular weight of these particles, which caused
      unfavorably large NMR line widths. We have recently constructed truncated
      versions of the membrane scaffold protein, allowing the preparation of a range of
      stepwise-smaller nanodiscs (6- to 8-nm diameter) to overcome this limitation.
      Here, we present a protocol on the assembly of phospholipid nanodiscs of various
      sizes for structural studies of membrane proteins with solution-state NMR
      spectroscopy. We describe specific isotope-labeling schemes required for working
      with large membrane protein systems in nanodiscs, and provide guidelines on the
      setup of NMR non-uniform sampling (NUS) data acquisition and high-resolution NMR
      spectra reconstruction. We discuss critical points and pitfalls relating to
      optimization of nanodiscs for NMR spectroscopy and outline a strategy for the
      high-resolution structure determination and positioning of isotope-labeled
      membrane proteins in nanodiscs using nuclear Overhauser enhancement spectroscopy
      (NOESY) spectroscopy, residual dipolar couplings (RDCs) and paramagnetic
      relaxation enhancements (PREs). Depending on the target protein of interest,
      nanodisc assembly and purification can be achieved within 12-24 h. Although the
      focus of this protocol is on protein NMR, these nanodiscs can also be used for
      (cryo-) electron microscopy (EM) and small-angle X-ray and neutron-scattering
      studies.

PMID- 29215633
TI  - Measuring mutation accumulation in single human adult stem cells by whole-genome
      sequencing of organoid cultures.
AB  - Characterization of mutational processes in adult stem cells (ASCs) will improve
      our understanding of aging-related diseases, such as cancer and organ failure,
      and may ultimately help prevent the development of these diseases. Here, we
      present a method for cataloging mutations in individual human ASCs without the
      necessity of using error-prone whole-genome amplification. Single ASCs are
      expanded in vitro into clonal organoid cultures to generate sufficient DNA for
      accurate whole-genome sequencing (WGS) analysis. We developed a data-analysis
      pipeline that identifies with high confidence somatic variants that accumulated
      in vivo in the original ASC. These genome-wide mutation catalogs are valuable
      resources for the characterization of the underlying mutational mechanisms. In
      addition, this protocol can be used to determine the effects of culture
      conditions or mutagen exposure on mutation accumulation in ASCs in vitro. Here,
      we describe a protocol for human liver ASCs that can be completed over a period
      of 3-4 months with hands-on time of ~5 d.

PMID- 29215636
TI  - Poly(A) tails: longer is not always better.

PMID- 29215634
TI  - Expansion of patient-derived circulating tumor cells from liquid biopsies using a
      CTC microfluidic culture device.
AB  - The development of personalized cancer therapy depends on a robust system to
      monitor the patient's individual response to anticancer treatment. Anticancer
      drug efficacy has been tested on circulating tumor cells (CTCs) derived from
      patient blood samples after ex vivo expansion into CTC clusters. Current attempts
      to culture these primary cancer cells focus on long-term maintenance under growth
      factor supplements into cell lines, which usually takes >6 months and results in
      a CTC expansion efficiency of <20%. We recently developed a simple but unique
      microfluidics-based culture approach that requires minimal preprocessing (~30
      min) and does not require prior enrichment of CTCs or depend on the use of growth
      factor supplements. The approach capitalizes on co-culture of immune cells from
      the same patient blood sample within specially designed microwells that promote
      CTC cluster formation within 2 weeks, with an overall cluster formation success
      rate of ~50%. Drug screening is facilitated by the incorporation of a gradient
      generator for parallel exposure to two or more drugs at various concentrations.
      Owing to the cost-effectiveness and less-invasive nature of this procedure,
      routine monitoring of disease progression can be achieved. The described
      microfluidics system can be operated with a single syringe pump to introduce drug
      compounds (which takes ~6 min), followed by incubation of the CTC clusters for 48
      h before analysis. In addition to its applications in biomedical research, the
      rapid readout of our platform will enable clinicians to assess or predict a
      patient's response to various therapeutic strategies, so as to enable
      personalized or precision therapy.

PMID- 29215637
TI  - One flexible loop in OST lassos both substrates.

PMID- 29215638
TI  - Poltheta helicase: drive or reverse.

PMID- 29215635
TI  - Mapping the small RNA interactome in bacteria using RIL-seq.
AB  - Small RNAs (sRNAs) are major post-transcriptional regulators of gene expression
      in bacteria. To enable transcriptome-wide mapping of bacterial sRNA-target pairs,
      we developed RIL-seq (RNA interaction by ligation and sequencing). RIL-seq is an
      experimental-computational methodology for capturing sRNA-target interactions in
      vivo that takes advantage of the mutual binding of the sRNA and target RNA
      molecules to the RNA chaperone protein Hfq. The experimental part of the protocol
      involves co-immunoprecipitation of Hfq and bound RNAs, ligation of RNAs, library
      preparation and sequencing. The computational pipeline maps the sequenced
      fragments to the genome, reveals chimeric fragments (fragments comprising two
      ligated independent fragments) and determines statistically significant
      overrepresented chimeric fragments as interacting RNAs. The statistical filter is
      aimed at reducing the number of spurious interactions resulting from ligation of
      random neighboring RNA fragments, thus increasing the reliability of the
      determined sRNA-target pairs. A major advantage of RIL-seq is that it does not
      require overexpression of sRNAs; instead, it simultaneously captures the in vivo
      targets of all sRNAs in the native state of the cell. Application of RIL-seq to
      bacteria grown under different conditions provides distinctive snapshots of the
      sRNA interactome and sheds light on the dynamics and rewiring of the post
      transcriptional regulatory network. As RIL-seq needs no prior information about
      the sRNA and target sequences, it can identify novel sRNAs, along with their
      targets. It can be adapted to detect protein-mediated RNA-RNA interactions in any
      bacterium with a sequenced genome. The experimental part of the RIL-seq protocol
      takes 7-9 d and the computational analysis takes ~2 d.

PMID- 29215639
TI  - The ribosome moves: RNA mechanics and translocation.
AB  - During protein synthesis, mRNA and tRNAs must be moved rapidly through the
      ribosome while maintaining the translational reading frame. This process is
      coupled to large- and small-scale conformational rearrangements in the ribosome,
      mainly in its rRNA. The free energy from peptide-bond formation and GTP
      hydrolysis is probably used to impose directionality on those movements. We
      propose that the free energy is coupled to two pawls, namely tRNA and EF-G, which
      enable two ratchet mechanisms to act separately and sequentially on the two
      ribosomal subunits.

PMID- 29215640
TI  - Catching DNA with hoops-biophysical approaches to clarify the mechanism of SMC
      proteins.
AB  - Structural maintenance of chromosome (SMC) complexes are central regulators of
      chromosome architecture that are essential in all domains of life. For decades,
      the structural biology field has been debating how these conserved protein
      complexes use their intricate ring-like structures to structurally organize DNA.
      Here, we review the contributions of single-molecule biophysical approaches to
      resolving the molecular mechanism of SMC protein function.

PMID- 29215643
TI  - Management of ophthalmologic manifestations of mitochondrial diseases.

PMID- 29215645
TI  - Cherchez la femme: maternal incidental findings can explain discordant prenatal
      cell-free DNA sequencing results.
AB  - Circulating DNA fragments in a pregnant woman's plasma derive from three sources:
      placenta, maternal bone marrow, and fetus. Prenatal sequencing to noninvasively
      screen for fetal chromosome abnormalities is performed on this mixed sample;
      results can therefore reflect the maternal as well as the fetoplacental DNA.
      Although it is recommended that pretest counseling include the possibility of
      detecting maternal genomic imbalance, this seldom occurs. Maternal abnormalities
      that can affect a prenatal screening test result include disorders that affect
      the size and metabolism of DNA, such as B12 deficiency, autoimmune disease, and
      intrahepatic cholestasis of pregnancy. Similarly, maternal tumors, both benign
      and malignant, can release DNA fragments that contain duplications or deletions.
      Bioinformatics algorithms can subsequently interpret the raw sequencing data
      incorrectly, resulting in false-positive test reports of fetal monosomies or test
      failures. Maternal sex-chromosome abnormalities, both constitutional and somatic,
      can generate results that are discordant with fetal ultrasound examination or
      karyotype. Maternal copy-number variants and mosaicism for autosomal aneuploidies
      can also skew interpretation. A maternal etiology should therefore be considered
      in the differential diagnosis of prenatal cell-free DNA test failures, false
      positive and false-negative sequencing results. Further study is needed regarding
      the clinical utility of reporting maternal incidental findings.

PMID- 29215644
TI  - Response to Newman et al.

PMID- 29215646
TI  - Follow-up status during the first 5 years of life for metabolic disorders on the
      federal Recommended Uniform Screening Panel.
AB  - PURPOSE: To investigate the 5-year follow-up status for newborns diagnosed with
      metabolic disorders designated as "primary disorders" on the federal Recommended
      Uniform Screening Panel (RUSP). METHODS: Follow-up status and demographic
      characteristics are described for 426 newborns diagnosed with one of 20 primary
      metabolic disorders on the RUSP between 2005 and 2009. Newborn screening program
      data were linked to birth certificate data. Follow-up status is described for
      each year through age 5 and by disorder type. Maternal characteristics of those
      who stayed in active care were compared with those who did not. RESULTS: Of 426
      diagnosed newborns, by the end of 5 years of follow-up 55.2% stayed in active
      care, 20.4% became lost to follow-up, 8.7% moved out of state, 6.3% were
      determined to require no further follow-up, 4.7% refused follow-up, and 4.7%
      died. Among the initial group of disorders with more than 10 diagnosed cases,
      phenylketonuria (90%) had the highest percentage of patients still in active care
      after 5 years. Patients in active care had similar characteristics to patients
      not in active care when maternal age, race/ethnicity, completed education years,
      and expected source of payment for delivery were compared. CONCLUSION: Staying in
      active care may associate with disorder type but not maternal characteristics.

PMID- 29215647
TI  - Fragile X population carrier screening.

PMID- 29215648
TI  - Happy birthday, Genetics in Medicine!

PMID- 29215649
TI  - A craniosynostosis massively parallel sequencing panel study in 309 Australian
      and New Zealand patients: findings and recommendations.
AB  - PURPOSE: The craniosynostoses are characterized by premature fusion of one or
      more cranial sutures. The relative contribution of previously reported genes to
      craniosynostosis in large cohorts is unclear. Here we report on the use of a
      massively parallel sequencing panel in individuals with craniosynostosis without
      a prior molecular diagnosis. METHODS: A 20-gene panel was designed based on the
      genes' association with craniosynostosis, and clinically validated through
      retrospective testing of an Australian and New Zealand cohort of 233 individuals
      with craniosynostosis in whom previous testing had not identified a causative
      variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76
      individuals were tested prospectively. RESULTS: Pathogenic or likely pathogenic
      variants in non-FGFR genes were identified in 43 individuals, with diagnostic
      yields of 14% and 15% in retrospective and prospective cohorts, respectively.
      Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8),
      typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1
      negative clinically suspected Saethre-Chotzen syndrome. Clinically significant
      variants were also identified in ALX4, EFNA4, ERF, and FGF10. CONCLUSION: These
      findings support the clinical utility of a massively parallel sequencing panel
      for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for
      nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen
      syndrome.

PMID- 29215650
TI  - Phenocopies in melanoma-prone families with germ-line CDKN2A mutations.
AB  - PURPOSE: Carriers of CDKN2A mutations have high risks of melanoma and certain
      other cancers. In this study we examined the occurrence of tumors among CDKN2A
      wild type (wt) members of melanoma-prone families with CDKN2A mutations. METHODS:
      Swedish and US melanoma-prone families with CDKN2A mutations were included. Data
      was collected on tumors diagnosed among family members. Among the CDKN2A mutated
      families, members with CDKN2A wt status who were diagnosed with melanoma were
      designated phenocopies. RESULTS: Of patients with melanoma in the CDKN2A mutated
      families (n = 266), 7.1%, were seen among members with CDKN2A wt status
      (phenocopy rate). Among the CDKN2A wt family members of the CDKN2A mutated
      families (n = 256), 7.4% were diagnosed with melanoma. The prospective relative
      risk for melanomas was significantly higher among the CDKN2A wt subjects compared
      with population-based controls (7.4 (95% confidence interval 1.7-33.2)), while no
      elevated risks of nonmelanoma cancers were seen and their offspring did not have
      significantly elevated risks of melanoma or other cancers. CONCLUSION: Members of
      CDKN2A mutation carrying families who test negative for their family's mutation
      have moderately increased risk for melanoma and should, in addition to being
      considered for continuing dermatologic surveillance, be encouraged to follow sun
      safety recommendations and practice skin self-exams.

PMID- 29215651
TI  - Mosaic disorders and the Taxonomy of Human Disease.

PMID- 29215652
TI  - Corrigendum: Sources of discordance among germ-line variant classifications in
      ClinVar.
AB  - This corrects the article DOI: 10.1038/gim.2017.60.

PMID- 29215653
TI  - Prevalence of neurofibromatosis type 1 in the Finnish population.
AB  - PURPOSE: The incidence of neurofibromatosis 1 (NF1) is ~1/2,000 live births, but
      the current estimates of prevalence vary greatly. This retrospective total
      population study was aimed at determining the prevalence of NF1 in Finland.
      METHODS: All secondary and tertiary referral centers of Finland were searched for
      NF1 patients. Patient records were manually reviewed and patients fulfilling the
      National Institutes of Health diagnostic criteria for NF1 were included.
      Prevalence on 31 December 2005 was determined. Data on incidence and survival
      were combined to refine the prevalence estimation. RESULTS: A total of 1,279
      patients with NF1 were alive on 31 December 2005, yielding a prevalence of
      1/4,088 (95% confidence interval (CI) 1/4,320-1/3,869). The survival of patients
      with NF1 was inferior compared with the general population (hazard ratio 3.10,
      95% CI 2.73-3.53, P < 0.001). When the survival rates of NF1 patients and the
      Finnish population were combined with an estimate of NF1 incidence, a prevalence
      of 1/2,052 (95% CI 1/2,176-1/1,941) was estimated for NF1 in a population aged 0
      74 years. CONCLUSION: NF1 is a much more common disorder than previously thought.
      A large proportion of NF1 patients may not be correctly identified by health-care
      systems or they do not seek secondary health care for their NF1.

PMID- 29215654
TI  - Age and perceived risks and benefits of preventive genomic screening.
AB  - PURPOSE: As genome sequencing moves from research to clinical practice,
      sequencing technologies focused on "medically actionable" targets are being
      promoted for preventive screening despite the dearth of systematic evidence of
      risks and benefits and of criteria for selection of screening subjects. This
      study investigates researchers' and research participants' perceptions of these
      issues within the context of a preventive genomic screening study, GeneScreen.
      METHODS: We recorded researcher deliberations regarding age eligibility criteria
      and the risks and benefits of screening, and conducted interviews with 50
      GeneScreen participants about their motivations for joining and their perceptions
      of risks and benefits. RESULTS: Researchers made assumptions about who would want
      and benefit from screening based on age. After discussion, researchers opted not
      to have an upper age limit for enrollment. Participants of all ages perceived
      similar benefits, including prevention, treatment, and cascade testing, and
      similar risks, such as insurance discrimination and worry. CONCLUSION: While
      clinical benefits of preventive genomic screening for older adults are debatable,
      our respondents perceived a range of benefits of screening in both clinical and
      research settings. Researchers and clinicians should carefully consider decisions
      about whether to exclude older adults and whether to provide information about
      benefits and risks across age groups.

PMID- 29215655
TI  - Observed frequency and challenges of variant reclassification in a hereditary
      cancer clinic.
AB  - PurposeEfforts have been made by the American College of Medical Genetics and
      Genomics and the Association for Molecular Pathology to make variant
      classification more uniform, but many limitations remain. Reclassification of a
      variant of uncertain significance (VUS) is expected, but other more certain
      calls, like pathogenic or benign, can also be reclassified once additional
      information is gathered. Variant reclassification can create difficult
      circumstances for both patients and clinicians.MethodsRetrospective review of all
      variant reclassifications in genes associated with hereditary cancer syndromes at
      one clinic between September 2013 and February 2017 was completed. All variant
      reclassifications were completed and reported by the original testing
      laboratory.ResultsA total of 1,103 hereditary cancer tests were ordered. Fewer
      than 5% (40/1,103) of the initial reports were updated during that time period.
      Most reclassifications (29/40) were downgrades of VUS to likely benign. Only
      three reclassifications could potentially alter medical management.ConclusionThe
      majority of variant reclassifications do not impact medical management. Upgrading
      a variant call to pathogenic could be important for a patient's care and shows
      the importance of open communication between laboratories and clinicians. A
      variant downgrade from pathogenic can be a significant reclassification as well,
      especially if prophylactic surgery has been completed.

PMID- 29215656
TI  - [Control of cardiovascular risk factors in type 2 diabetes in a specialized
      diabetic clinic].
AB  - BACKGROUND: Achieving an adequate control of glycaemic and cardiovascular risk
      factors (CVRFs) is essential in patients with type 2 diabetes mellitus (T2DM).
      However, several studies have shown that the percentage of patients achieving
      these goals is scarce. We evaluated the degree of control of CVRFs target goals
      in T2DM patients who regularly attend a specialized diabetic clinic. METHODS: We
      studied T2DM patients who attended the specialized Diabetic Unit at the
      Department of Endocrinology of Clinica Universitaria de Navarra with a minimum
      follow-up of one year. Clinical characteristics, chronic complications and
      treatments were collected and patients were classified into groups according to
      the fulfilment of target glycated haemoglobin (HbA1c), LDL cholesterol and blood
      pressure (BP) levels, predefined according to the presence of different
      comorbidities and the duration of T2DM. RESULTS: We analysed 137 patients (75%
      men) with T2DM, with an average age of 67 years and a 12.7 year duration of
      diabetes. During follow-up, 83.9% of the patients were within the individualized
      HbA1c target, 76.6% considering BP and 67.2% in terms of LDL-cholesterol. In
      addition, 68% had concomitantly the three main variables within the target.
      CONCLUSIONS: In our population of T2DM, HbA1c, LDL cholesterol and BP targets
      were achieved in a substantial proportion of patients (67-91%). Perhaps the
      intense and individualized care offered through a specialized diabetes unit may
      explain these results.

PMID- 29215657
TI  - [The patient and the crossing between Primary and Hospital care. Systematic
      review of trials for the implementation of tools for integration in Spain].
AB  - BACKGROUND: Health services are moving towards a complete integration to try and
      reduce fragmentation, increase efficiencies and improve health outcomes.
      Estimates the effectiveness in of different tools for integrated care in Spain.
      METHODS: We performed a systematic review of articles using MEDLINE (last search
      July31st, 2017). Randomized clinical trials reporting health outcomes of tools
      for integrated care used in Spain were included. Studies were appraised for
      quality using the Cochrane Risk of Bias assessment. RESULTS: Twenty studies met
      the criteria for the systematic review. Interventions included were hospital-at
      home (four studies, 455 patients), outpatient clinic by videoconference (three
      studies, 2438 patients), nurse navigator (four studies, 1051 patients), self-care
      improvement (four studies, 1291 patients), at-home health monitoring (three,
      162), health apps (two, 225) and medical reconciliation (one, 172). Hospital-at
      home, nurse navigator or self-care improvement reduced readmission rate in older
      patients, heart failure (HF) or chronic obstructive pulmonary disease (COPD).
      Self-care improvement and nurse navigator reduced mortality rate in HF. Hospital
      at-home reduced hospital stay in COPD. Self-care improvement reduced outpatient
      visits in asthma patients. Outpatient video by videoconference reduced time to
      diagnosis and treatment in rural areas. The quality of the evidence ranged from
      low to very low for all the outcomes because it was based in double or triple
      downgraded randomized trials. CONCLUSION: The implementation of tools for
      integrated care in Spain improved some outcomes of relevance in patients with
      chronic conditions, although evidence is low. Self-care improvement stood out due
      to the improvements made.

PMID- 29215658
TI  - [Suicide: the challenge of prevention].

PMID- 29215659
TI  - [Influence of sociodemographic, occupational and life style factors on the levels
      of burnout in palliative care health professionals].
AB  - BACKGROUND: Palliative care health professionals have reported high levels of
      burnout. An understanding of factors associated with this syndrome in this
      population could foster new prevention and intervention strategies. The
      objectives were to evaluate the levels of burnout in each of its dimensions in a
      sample of palliative care health professionals and to analyze the relationship
      between levels of burnout and sociodemographic, occupational and lifestyle
      characteristics in this sample. METHODS: The total sample was composed of 92
      palliative care health professionals. Sociodemographic, occupational and
      lifestyle characteristics were registered. The levels of burnout syndrome were
      evaluated by the Maslach Burnout Inventory - Human Services Survey (MBI-HSS). The
      total sample was divided into three groups, depending on the level of burnout
      (non-burnout group, burnout group meeting one criterion, and burnout group
      meeting two or three criteria). Comparisons were performed amongst groups for all
      characteristics evaluated. RESULTS: The non-burnout professionals were
      significantly older and slept more than the professionals with more than one
      altered dimension; in addition, they had greater job seniority in the unit than
      those with a single altered dimension and did physical exercise more frequently
      than either of the burnout groups. CONCLUSION: The younger professionals, with
      more job seniority in the units of palliative care, and less hours of sleep and
      physical activity showed higher levels of burnout. Therefore, these factors
      should be considered for enhancing prevention and intervention strategies for
      these health professionals.

PMID- 29215660
TI  - [Prioritization of non-recommended clinical activities in Primary Care].
AB  - OBJECTIVE: To prioritize non-recommended clinical activities in Primary Care
      (PC), from "Do not do" recommendations listed by the Sociedad Espanola de
      Medicina de Familia y Comunitaria (Semfyc), according to expert consensus
      (physicians, nurses and pharmacists). METHODS: The consensus for the
      prioritization of non-recommended practices in PC was performed through an online
      procedure. We used as a base the list of "do not-do" recommendations of the
      SEMFYC. We asked the experts to prioritize practices that should be de-adopted in
      PC, based on four prioritization criteria: frequency of occurrence, cost of the
      activity, ease of disposal and damage caused, which were scored from one to five,
      according to their recommendation. Scores were summarized in median and quartile
      values. Two rounds were necessary to obtain a consensus. A modified e-Delphi
      technique was used. RESULTS: 34 experts (62%) participated in the first
      consultation round and prioritized 19 recommendations with a score = 3.5. These
      recommendations were again analyzed in a second round, in which 32 panelists
      agreed to prioritize 17 practices (13 related to prescription, three diagnostic
      tests, and one clinical analysis). The high priority list included seven
      practices with values = 4: 1) Prescription of a new drug in elderly patients
      without having reviewed the previous treatments; 2) Lipid-lowering drugs without
      calculating the overall cardiovascular risk; 3) Not systematically prescribing
      gastric protection with proton pump inhibitors to patients consuming Nonsteroidal
      anti-inflammatory drugs (NSAIDs); 4) Glucose self-analysis in non-insulinized
      type 2 diabetics; 5) Benzodiazepines in the long term; 6) Bisphosphonates in
      patients with low risk of fracture; and 7) Antibiotics in lower respiratory tract
      infections. CONCLUSION: This study provides information for the prioritization of
      17 non-AP activities in which short-term de-adoption would significantly increase
      the efficiency of the public health system.

PMID- 29215661
TI  - [Horner's Syndrome: an unusual ophthalmological presentation of Hodgkin
      lymphoma].
AB  - Horner's Syndrome (HS) is a neurological syndrome characterised by the triad
      incomplete pupillary miosis, palpebral ptosis and facial anhidrosis, due to a
      lesion of the oculosympathetic pathway, formed of three neurons from the
      hipothalamus to the eye. Identifying its cause is a diagnostic challenge since in
      spite of its apparent lack of clinical importance, HS can be the first or only
      manifestation of a serious, or even potentially mortal disorder. We present the
      case of a 19-year-old male patient with a history of nonspecific ocular pains of
      two months evolution. He attended the emergency ophthalmological clinic where he
      was diagnosed with an HS as the first clinical manifestation of Hodgkin lymphoma.

PMID- 29215662
TI  - [Validation of the Scale of Hope in Terminal Illness for relatives brief version
      (SHTI-b). Validity and reliability analysis.]
AB  - BACKGROUND: Bermejo and Villacieros' Scale of Hope in Terminal Disease (SHTD)
      specifically collects meanings of hope facing terminal disease, including
      considerations relating to psycho-emotional support and that have a
      transcendental sense. The objective of this paper is to validate the SHTD
      abbreviated and rephrased to adapt all the items to a single domain. METHODS:
      Starting from the published SHTD, an exploratory factor analysis (EFA) was
      carried out with a sample of 177 valid questionnaires. In a second study, with
      another sample of 180 valid questionnaires, a confirmatory factor analysis (CFA)
      and a correlation analysis with other measurements of spiritual wellbeing
      (Functional Assessment of Chronic Illness Therapy-Sp) and hope (Herth Hope Index)
      were done. RESULTS: A bidimensional model with satisfactory goodness of fit index
      values was obtained (GFI = 0.991; CFI = 0.984; SRMR = 0.08; RMSEA = 0.057); the
      Relations of Transcendence factor obtained a Cronbach's alpha of 0.872 and
      Personal Relations an alpha of 0.762. The correlations of the SHTI-rb with
      external measures were: r = 0.527with FACIT; r = 0.266 with HHI; r = 0.667 with
      the Spirituality subscale of FACIT; and r = 0.348 with the Interrelation factor
      of HHI. The Relations of Transcendence subscale correlated with both Layout and
      Expectation and Interrelation of HHI (r = 0.162 and r = 0.329 respectively),
      while the scale of Personal Relations only correlated with Interrelation of HHI
      (r = 0.244). CONCLUSIONS: The Scale of Hope in Terminal Illness for relatives
      (brief version) is a valid and reliable specific instrument for terminal
      patients.

PMID- 29215663
TI  - Conducting Behavioral Intervention Research in Rural Communities: Barriers and
      Strategies to Recruiting and Retaining Heart Failure Patients in Studies.
AB  - Background: Heart failure is a major public health problem, and self-management
      is the primary approach to control the progression of heart failure. The low
      research participation rate among rural patients hinders the generation of new
      evidence for improving self-management in rural heart failure patients. Purpose:
      The purpose of this study is to identify the barriers and strategies in the
      recruitment and retention of rural heart failure patients in behavioral
      intervention programs to promote self-management adherence. Method: This is a
      descriptive study using data generated from a randomized controlled trial.
      Results: Eleven common barriers were identified such as the inability to perceive
      the benefits of the study, the burden of managing multiple comorbidities, and the
      lack of transportation to appointments. Possible gateways to improve recruitment
      and retention include using recruiters from the local community and promoting
      provider engagement with research activities. Multiple challenges inhibited rural
      heart failure patients from participating in and completing the behavioral
      intervention study. Conclusion and implications: Anticipation of those barriers,
      and identifying strategies to remove those barriers, could contribute to an
      improvement in the rural patients' participation and completion rates, leading to
      the generation of new evidence and better generalizability of the evidence.

PMID- 29215664
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1590/S1980-57642009DN30400010.].

PMID- 29215665
TI  - [RETRACTED ARTICLE]: Culture as a variable in neuroscience and clinical
      neuropsychology: A comprehensive review.
AB  - [This retracts the article DOI: 10.1590/1980-57642015DN93000002.].

PMID- 29215666
TI  - Sample preparation for polar metabolites in bioanalysis.
AB  - Sample preparation is a primary step of any bioanalytical workflow, especially in
      metabolomics analysis where maximum information has to be obtained without
      spoiling the analytical instrument. Because of their biological implication,
      highly polar metabolites, such as amino acids, nucleobases, and catecholamines
      seem to attract growing interest in the field of comprehensive metabolomics
      analysis although their extraction from the matrix remains a real challenge. In
      this paper, we discuss about the actual practice and issues of hydrophilic
      metabolites' extraction, including new solutions and perspectives to improve
      their phase transfer from a complex biological sample to a clean extract prior to
      analysis.

PMID- 29215667
TI  - A general and efficient approach for tuning the crystal morphology of classical
      MOFs.
AB  - This communication introduces a general approach toward the size/morphology
      controlled synthesis of classical MOFs with 2-methylimidazole (2-MI) as a
      competitive ligand and a base to accelerate the nucleation of crystallization. A
      higher concentration of 2-MI and a suitable polarity and solubility of the
      solvent will accelerate the nucleation of the crystal, resulting in nanometer
      size particles. However, larger crystals can be obtained via the further growth
      of nanoparticles with prolonging the reaction time. Such a serendipitous
      discovery may inspire future researchers to design new MOF materials with desired
      structures.

PMID- 29215668
TI  - Radiolytic stability of N,N-dialkyl amide: effect on Pu(iv) complexes in
      solution.
AB  - The radiolytic degradation of three N,N-dialkyl amide ligands relevant to nuclear
      fuel reprocessing was studied. The degradation of these ligands: N,N di-2
      ethyhexylbutyramide (DEHBA), N,N di-2-ethyhexylisobutyramide (DEHiBA) and N,N di
      2-ethyhexyl-3-dimethylbutanamide (DEHDMBA) was examined to evaluate the effect of
      the structure on the formation of degradation products as well as to compare
      alpha induced degradation to gamma induced degradation. In situ alpha radiolysis
      by introduction of plutonium(iv) as the alpha source in the solution and ex situ
      gamma radiolysis with 60Co as the gamma source were compared. Upon identification
      of the main degradation products, a degradation scheme was proposed. The effects
      of radiation on the stability of Pu-monoamide complexes were discussed.
      Theoretical calculations were also performed to determine bond dissociation
      energy and estimate the relative strength of the bond in the molecule. The
      results show that neither the type of radiation (alpha vs. gamma) nor the
      structure modification (introduction of branching on the alkyl chain off the
      carbonyl carbon) of the molecule significantly impact the formation of
      degradation products under the conditions studied. Moreover, it was observed that
      the overall stability of the monoamide remains good and that Pu complexation is
      not greatly affected by either alpha or gamma irradiation.

PMID- 29215669
TI  - A core-shell structured LiNi0.5Mn1.5O4@LiCoO2 cathode material with superior rate
      capability and cycling performance.
AB  - A core-shell structured LiNi0.5Mn1.5O4@LiCoO2 cathode material has been
      successfully synthesized by the combination of sol-gel and solid state methods.
      The coating of LiCoO2 has a significant effect on the electrochemical performance
      of the spinel LiNi0.5Mn1.5O4-based cathode material, especially the cycling
      stability at high temperature and rate capability. After modification, the ionic
      conductivity of the material is greatly improved due to the high ion conductivity
      of LiCoO2. The LiNi0.5Mn1.5O4@LiCoO2 with 1% LiCoO2 presents the optimal rate
      capability and delivers a relatively high discharge capacity of 122 mA h g-1 at
      10C. On the other hand, the surface coating of LiCoO2 can effectively facilitate
      Li+ interfacial diffusion, and alleviate the side reactions between the active
      material and the electrolyte; as a result, the capacity retention of 96.17% for
      the LiNi0.5Mn1.5O4@LiCoO2 electrode with 1% LiCoO2 is much higher than that for
      the bare LiNi0.5Mn1.5O4 (74.93%) after 100 cycles at elevated temperature. Our
      study confirms that the core-shell structure construction caused by the coating
      of LiCoO2 plays a critical role in the improvement of the electrochemical cycling
      stability at elevated temperatures and rate capability.

PMID- 29215670
TI  - Is a strong axial crystal-field the only essential condition for a large magnetic
      anisotropy barrier? The case of non-Kramers Ho(iii) versus Tb(iii ).
AB  - A monometallic non-Kramers Ho(iii) complex with a strong uniaxial ligand field
      displays a record high energy barrier of 355 K with hysteresis opening up to 4 K
      at a sweep rate of 0.027 T s-1, while the isomorphous, more anisotropic non
      Kramers Tb(iii) complex displays strong quantum tunnelling between the ground
      states. Ab initio calculations reveal that the presence of strong axial ligands
      and moderately weaker equatorial ligands is sufficient to quench the QTM between
      the ground pseudo doublets (mJ = +/-8) in the case of Ho(iii) complex, where the
      relaxation is found to proceed via the first excited state. However, the
      equatorial field disrupts the stabilization of ground pseudo doublets in Tb(iii),
      inducing QTM and inhibiting SIM behaviour. Further insights into the decisive
      role played by the secondary coordination sphere and hydrogen-bonding in the SIM
      characteristics of these two non-Kramers ions were also gained. This combined
      experimental and computational approach highlights that although strong axiality
      holds the key for designing high temperature SIMs based on oblate non-Kramers
      ions, the strength of the equatorial ligand field also cannot be ignored.

PMID- 29215671
TI  - The role of structure and the metal ion in the fluorescence sensing of nitro
      compounds for a series of lanthanide(iii) 9,10-anthracene dicarboxylate
      coordination polymers.
AB  - Twenty-eight lanthanide coordination polymers (CPs) containing 9,10-anthracene
      dicarboxylate (ADC) linkers have been synthesized and characterized. For the
      earlier class of lanthanides La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+ and Tb3+,
      the 3D pcu net was generated from dimethylformamide (DMF) while a 2D hcb net was
      formed using dimethylacetamide (DMA). Similarly for the later class of
      lanthanides, Dy3+, Ho3+, Er3+, Tm3+, Yb3+ and Lu3+, a 2D hcb net was formed when
      dimethylacetamide (DMA) was used. However, the formation of a crystalline product
      with DMF was possible only when DMSO was added together for these lanthanides,
      and they yielded 2D structures despite the usage of DMF. Only the single crystal
      structures of Er3+ and Ho3+ have been determined and the rest of the structures
      were confirmed by PXRD studies. These compounds have been used to sense various
      nitro compounds. In particular, they are the most sensitive to Brady's reagent,
      2,4-dinitrohydrazobenzene. There was no difference in the quenching extent
      between the 3D and 2D early lanthanide CPs. For the later lanthanides which adopt
      2D structures, the quenching efficiency is higher when DMA instead of DMSO is
      coordinated suggesting the solvent effect in emission quenching.

PMID- 29215672
TI  - Design of two isoreticular Cd-biphenyltetracarboxylate frameworks for dye
      adsorption, separation and photocatalytic degradation.
AB  - Two novel isoreticular cadmium metal-organic frameworks (MOFs) with the framework
      formula of [Cd2(BPTC)(solvent)3] (H4BPTC = 3,3',5,5'-biphenyltetracarboxylic
      acid) have been constructed under diverse reaction conditions and characterized
      by single crystal X-ray diffraction, PXRD, IR and TGA. The neutral 3D frameworks
      of 1 and 2 with one-dimensional (1D) rhombic channels exhibit both distinct
      uptake and good selectivity for cationic methylene blue (MB) dye molecules. The
      adsorption capacity and adsorption kinetic constant of 2 are greater than those
      of 1, showing the importance of porosity and pore size during the adsorption.
      Moreover, both MOFs show effective degradation of rhodamine B (RhB) and methyl
      orange (MO) dyes under UV light irradiation.

PMID- 29215673
TI  - Extraction of triterpenoids and phenolic compounds from Ganoderma lucidum:
      optimization study using the response surface methodology.
AB  - The extraction of triterpenoids and phenolic compounds from Ganoderma lucidum was
      optimized by using the response surface methodology (RSM), using heat and
      ultrasound assisted extraction techniques (HAE and UAE). The obtained results
      were compared with that of the standard Soxhlet procedure. RSM was applied using
      a circumscribed central composite design with three variables (time, ethanol
      content, and temperature or ultrasonic power) and five levels. The conditions
      that maximize the responses (extraction yield, triterpenoids and total phenolics)
      were: 78.9 min, 90.0  degrees C and 62.5% ethanol and 40 min, 100.0 W and 89.5%
      ethanol for HAE and UAE, respectively. The latter was the most effective,
      resulting in an extraction yield of 4.9 +/- 0.6% comprising a content of 435.6 +/
      21.1 mg g-1 of triterpenes and 106.6 +/- 16.2 mg g-1 of total phenolics. The
      optimized extracts were fully characterized in terms of individual phenolic
      compounds and triterpenoids by HPLC-DAD-ESI/MS. The recovery of the above
      mentioned bioactive compounds was markedly enhanced using the UAE technique.

PMID- 29215674
TI  - Bioinspired dynamic microcapsules.
AB  - There is an increasing interest in bioinspired dynamic materials. Abundant
      illustrations of protein domains exist in nature, with remarkable ligand binding
      characteristics and structures that undergo conformational changes. For example,
      calmodulin (CaM) can have three conformational states, which are the unstructured
      Apo-state, Ca2+-bound ligand-exposed binding state, and compact ligand-bound
      state. CaM's mechanical response to biological cues is highly suitable for
      engineering dynamic materials. The distance between CaM globular terminals in the
      Ca2+-bound state is 5 nm and in the ligand-bound state is 1.5 nm. CaM's nanoscale
      conformational changes have been used to develop dynamic hydrogel microspheres
      that undergo reversible volume changes. The current work presents the fabrication
      and preliminary results of layer-by-layer (LbL) self-assembled Dynamic
      MicroCapsules (DynaMicCaps) whose multilayered shell walls are composed of
      polyelectrolytes and CaM. Quasi-dynamic perfusion results show that the
      DynaMicCaps undergo drastic volume changes, with up to ~1500% increase, when
      exposed to a biochemical ligand trifluoperazine (TFP) at pH 6.3. Under similar
      test conditions, microcapsules without CaM also underwent volume changes, with
      only up to ~290% increase, indicating that CaM's bio-responsiveness was retained
      within the shell walls of the DynaMicCaps. Furthermore, DynaMicCaps exposed to
      0.1 M NaOH underwent volume changes, with only up to ~580% volume increase.
      Therefore, DynaMicCaps represent a new class of polyelectrolyte multilayer (PEM)
      capsules that can potentially be used to release their payload at near
      physiological pH. With over 200 proteins that undergo marked, well-characterized
      conformational changes in response to specific biochemical triggers, several
      other versions of DynaMicCaps can potentially be developed.

PMID- 29215676
TI  - Analysis of the Epithelium-Mesenchymal Transition Process on Oral Squamous Cell
      Carcinomas.
AB  - The aim of this study is to evaluate the immunohistochemical expression of E
      cadherin, N-cadherin and Bmi-1, and their association with clinical parameters
      and with the degree of histopathological differentiation in oral squamous cell
      carcinomas. 65 squamous cell carcinoma samples were used for constructing a
      tissue microarray block, and then immunohistochemistry was performed for
      different markers. A semi-quantitative analysis of the amount of positive tumor
      cells was performed by two blind and calibrated observers (Kappa>0.75). The
      statistical Mann-Whitney and Kruskal-Wallis tests were used to evaluate the data.
      The correlation between variables was investigated by the Spearman test, and the
      significance level set at p<0.05. We observed higher expression of Bmi-1 in
      tumors located in the palate (p<0.0001). In addition, poorly differentiated
      tumors had a greater amount of Bmi-1 positive cells (p=0.0011). Regarding the
      other correlations between variables, no significant associations were detected.
      In conclusion, poorly differentiated squamous cell carcinomas located in the
      palate have higher immunostaining of Bmi-1, which can characterize activation of
      the Epithelial-Mesenchymal Transition process in these tumors.

PMID- 29215675
TI  - Association Between Apical Periodontitis and TNF-alpha -308 G>A Gene
      Polymorphism: A Systematic Review and Meta-Analysis.
AB  - Currently, investigations have focused on the identification of Single Nucleotide
      Polymorphisms (SNP) involved in host response and its ability to generate an
      immunity deficiency. The aim of this study was to perform a systematic review
      (SR) and meta-analysis to evaluate the association between TNF-alpha -308 G>A
      polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies
      was conducted. The following databases were used: PubMed, Scopus, Web of Science,
      and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms "Periapical
      Periodontitis," "Periapical Abscess," "Polymorphism, Genetic," and "Polymorphism,
      Single Nucleotide" were used. MeSH synonyms, related terms, and free terms were
      included. Clinical investigations of individuals with different AP phenotypes in
      permanent teeth were selected. After application of the eligibility criteria,
      selected studies were qualified by assessing their methodological quality. A
      fixed effect model was used for the meta-analysis. The initial search identified
      71 references. After excluding duplicate abstracts, 33 were selected. From these,
      two were eligible for quality assessment and were classified as being of moderate
      evidence. The included studies did not demonstrate association between AP and TNF
      alpha -308 G>A SNP. However, the meta-analysis demonstrated an association
      between the genotype distribution and AP phenotype (OR= 0.49; confidence
      interval= 0.25, 0.96; p=0.04). The role of TNF-alpha -308 G>A SNP in AP
      phenotypes is debatable. Further studies are needed to confirm and understand the
      underlying mechanisms of the identified association.

PMID- 29215677
TI  - Diabetic Rats Present High Mean Platelet Count in the Presence of Oral
      Infections.
AB  - Platelet count is associated with inflammatory diseases like diabetes mellitus
      (DM), which in turn, is related in a bidirectional manner with apical
      periodontitis and periodontal disease. The aim of this study was to evaluate the
      effects of apical periodontitis and/or periodontal disease on mean platelet count
      in a rat model of diabetes mellitus. Eighty Wistar rats were randomly divided
      into 8 groups (n=10): control (C), apical periodontitis (AP), periodontal disease
      (PD), apical periodontitis with periodontal disease (AP-PD), diabetes mellitus
      (DM), diabetes mellitus with apical periodontitis (DM-AP), diabetes mellitus with
      periodontal disease (DM-PD) and diabetes mellitus with apical periodontitis and
      periodontal disease (DM-AP-PD). Rats were anesthetized and DM was induced with a
      single dose of streptozotocin diluted in citrate buffer solution. After 6 days,
      the DM was confirmed. The animals were sedated and apical periodontitis was
      induced by dental exposure and periodontal disease was induced by periodontal
      ligature. After 30 days, animals were anesthetized and the blood was collected by
      cardiac puncture. Samples were processed and the mean platelet count was
      obtained. Data were tabulated and subjected to statistical analysis (p<0.05).
      Diabetic rats had higher mean glycemic levels compared with nondiabetic rats at 6
      and 36 days after DM induction (p<0.05). The DM-PD and DM-PD-AP groups showed
      increased mean platelet count compared to control and AP groups (p<0.05). The
      periodontal disease alone or associated with apical periodontitis influence mean
      platelet count in a rat model of diabetes mellitus.

PMID- 29215678
TI  - Decrease in Mandibular Cortical in Patients With Type 1 Diabetes Mellitus
      Combined with Poor Glycemic Control.
AB  - In this study we analyzed the mandibular cortical bone of patients with type 1
      diabetes mellitus (T1DM) and non-diabetic. Fifty patients with T1DM and 100 non
      diabetic ones paired by age and gender were analyzed. Two double-blinded
      observers evaluated 150 digital panoramic images of both groups. The mandibular
      cortical bone was analyzed using the Mandibular Cortical Index (MCI), Mental
      Index (MI), Gonial Index (GI), Antegonial Index (AI) and Upper and Lower
      Panoramic Mandibular Indexes (UPMI and LPMI), with the aid of RADIOIMP(r)
      software. Influence of T1DM in the morphology of the mandibular cortical bone was
      studied based on obtaining data related to T1DM diagnosis time, blood glucose
      level, T1DM control and the presence of chronic complications. Collected data
      were submitted to descriptive (mean and standard deviation) and inferential
      analyzes (Pearson's chi-squared test and Fisher's exact test) (p<=0.05).
      According to the MCI, individuals with T1DM had higher frequencies of mandibular
      cortical alterations, in both sexes and all age groups (p<0.01). For quantitative
      indexes, MI, GI, AI, UPMI and LPMI, female patients showed statistically
      significant differences for GI and AI, while male patients had statistically
      significant differences for all indexes (p<0.05), presenting the individuals with
      TDM1 inferior measures. Individuals with poor T1DM control showed significantly
      higher frequency of mandibular cortical alteration (92.3%), with lower means for
      MI, GI, AI and LPMI (p<=0.05). In conclusion, patients with T1DM showed decrease
      in the mandibular cortical bone when compared to non-diabetic ones, indicating
      that poor disease control is associated with these alterations.

PMID- 29215679
TI  - Accelerated Healing Period with Hydrophilic Implant Placed in Sheep Tibia.
AB  - The objective of this study was to evaluate the early osseointegration of two
      different implants surfaces, a sandblasted and acid-etched surface (TN) compared
      with same geometry and surface roughness modified to be hydrophilic/wettable by
      conditioning in an isotonic solution of 0.9% sodium-chloride (TA) through
      histological and histomorphometric analysis after sheep tibia implantation. Forty
      dental implants, divided in two groups (TN and TA) were placed in the left tibia
      of twenty healthy, skeletally mature Santa Ines sheep (n=5/experimental period).
      After 7, 14, 21 and 28 days post-implantation, the samples were removed and the
      sheep were kept alive. Analysis of resin sections (30 MUm) allowed the
      quantification of bone area (BA) and bone-to-implant contact (BIC). TA group
      presented nearly 50% increase in BA at 14 days (p<0.001, ANOVA - Tukey's post
      test) compared with 7 days. The TA presented higher values than the TN for BA and
      BIC at 14, 21, and 28 days after placement, stabilizing bone healing. TA
      hydrophilic surface promoted early osseointegration at 14 and 21 days compared to
      TN, accelerating bone healing period post-implant placement in sheep tibia.

PMID- 29215680
TI  - Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging
      and Histological Analysis.
AB  - The aim of this study was to assess the imaging and histological features of
      experimental periapical lesions, including the adjacent alveolar bone, in rats
      under zoledronic acid treatment. The study used 40 male Wistar rats distributed
      into 8 groups of 5 animals each: G1: induction of periapical lesion (PL) and
      weekly intraperitoneal administration (WIPA) of saline solution (0.9% NaCl) for 4
      weeks; G2: PL induction and WIPA of zoledronic acid (0.15 mg/kg/week) for 4
      weeks; G3: PL induction and WIPA of saline solution for 8 weeks; G4: PL induction
      and WIPA of zoledronic acid for 8 weeks; G5:WIPA of saline solution for 4 weeks
      and subsequent PL induction; G6: WIPA of zoledronic acid for 4 weeks and
      subsequent PL induction; G7: WIPA of saline solution for 8 weeks and subsequent
      PL induction; G8: WIPA of zoledronic acid for 8 weeks and subsequent PL
      induction. The administration of zoledronic acid or saline solution continued
      after PL induction until the euthanasia. Thus, cone beam computed tomography and
      histological analysis were performed. Statistical analyzes were performed by
      ANOVA and Kruskal-Wallis test. Groups treated with zoledronic acid showed
      significantly smaller size of PL than the groups treated with 0.9% NaCl (p<0.05).
      PLs were formed by chronic inflammation ranging from mild to moderate, with no
      difference between groups. In all specimens, no mandibular necrosis was observed.
      In conclusion, the presence of PLs apparently does not represent an important
      risk factor for the development of bisphosphonate-related osteonecrosis of the
      jaws.

PMID- 29215681
TI  - Oxygen Saturation in the Dental Pulp of Maxillary Premolars in Different Age
      Groups - Part 1.
AB  - The aim of this study was to determine oxygen saturation levels in the dental
      pulp of maxillary premolars in different age groups. A total of 120 human
      maxillary premolars with normal dental pulps were selected covering the following
      age groups: 20-24, 25-29, 30-34, 35-39 and 40-44 years (n=24 each group). Oxygen
      saturation was assessed using pulse oximetry. Analysis of variance was used to
      assess differences in oxygen saturation levels and Tukey's test was used to
      identify the age groups that differed from each other. Significance was set at
      0.05. Mean oxygen saturation of 120 premolars was 86.20% considering all age
      groups. Significantly reduced levels were found in the oldest group compared to
      the other groups: 40 to 44 years - 80.00% vs. 89.71, 87.67, 88.71, and 84.80% for
      age groups 20-24, 25-29, 30-34, 35-39 years, respectively. The mean oxygen
      saturation levels were similar between 20 and 39 years of age (86.20%) in the
      whole sample, but reduced significantly in the 40-44-year age group, suggesting
      that older patients present lower oxygen saturation results even in the absence
      of pulp tissue injury.

PMID- 29215682
TI  - Physicochemical and Biological Evaluation of Endodontic Filling Materials for
      Primary Teeth.
AB  - This study assessed the pH, radiopacity, antimicrobial effect, cytotoxicity and
      biocompatibility of endodontic filling materials for primary teeth. Zinc oxide
      eugenol (ZOE), Vitapex and Calen paste thickened with zinc oxide (ZO) were
      evaluated in comparison to an experimental MTA-based material. Radiopacity was
      tested using a graduated aluminum stepwedge with a digital sensor (n=5). The
      materials pH was recorded at 1, 4, 12 h; 1, 3, 7, 15 and 30 days (n=5). Direct
      contact test was used to assess the antimicrobial efficacy against Enterococcus
      faecalis after 1, 4, 12, 24 h (n=5). Cytotoxicity assay used MTT test for cell
      viability after incubation for 1, 3 and 7 days (n=5). For biocompatibility test,
      Wistar rats had received implants containing each material (n=5). The biopsied
      tissues were histologically analyzed after 15, 30 and 60 days. The results of
      radiopacity, pH, antimicrobial capacity and cytotoxicity were analyzed using
      ANOVA and Tukey tests. The histological data were submitted to Kruskal-Wallis
      test. The experimental material presented the lowest radiopacity (3.28 mm Al) and
      had a pH>12.0 throughout the test period. The experimental material showed the
      highest antibacterial effect, killing over 99.97% bacteria in 4 h. Vitapex
      presented the highest cell viability. Initially, biocompatibility test showed
      moderate to severe inflammation in all groups. After 60 days, Calen+ZO group
      showed moderate inflammation, while the others showed predominantly mild
      inflammatory reaction. The present results demonstrated that the experimental MTA
      based material exhibited satisfactory behavior regarding the studied properties.
      Additional in vivo studies are necessary for a better evaluation of the material.

PMID- 29215683
TI  - Instrument Design May Influence Bacterial Reduction During Root Canal
      Preparation.
AB  - The aim of this study was to evaluate the bacterial reduction promoted by
      ProTaper Next and Twisted File by comparing to ProTaper Universal and manual
      technique. Sixty distobuccal root canals of maxillary molars sterilized with
      ethylene oxide were contaminated with Enterococcus faecalis broth culture. After
      incubation for 21 days, bacterial samples were collected and cultured on m
      Enterococcus agar plates. The root canals were divided into 4 groups, according
      to the system used for instrumentation: ProTaper Next, Twisted File, ProTaper
      Universal, and crown down manual technique. Other 8 uncontaminated root canals
      were control asepsis. Bacterial samples were collected immediately and 7 days
      after instrumentation. The bacterial reduction was calculated and then made
      intragroup analysis by paired t-test and intergroup analysis by ANOVA and Tukey
      tests, all at 5% significance. All techniques significantly reduced the bacterial
      number in the root canal (p<0.05). ProTaper Next and Twisted File resulted in
      more bacterial reduction than ProTaper Universal and manual technique (p<0.05).
      ProTaper Next and Twisted File were similar (p>0.05). It can be concluded that
      ProTaper Next and Twisted File promote a higher bacterial reduction than Protaper
      Universal and manual technique.

PMID- 29215684
TI  - Radiopacity Evaluation of Gutta-Percha Points in Thinner Samples than the
      ANSI/ADA Recommendation.
AB  - The aim of this study was to evaluate the radiopacity of different gutta-percha
      points (Endo Points(r), Dentsply(r), Tanari(r), Meta(r), Roeko(r) and Odous(r))
      in samples of 1 mm thick as established by ANSI/ADA Specification #57 and ISO
      6876/2001, in comparison with thinner samples. Twelve test specimens for each
      material, four for each thickness (0.3, 0.6, and 1 mm and diameter of 8 mm), were
      laminated and compressed between two polished glass plates until the desirable
      thickness. Digital radiographs were obtained along with a graduated aluminum
      stepwedge varying from 1 to 10 mm in thickness. The X-ray unit was set at 70 kVp,
      10 mA and 0.4 s exposure time, at a focal distance of 36 cm. One calibrated
      observer quantified the average values of pixels with Adobe Photoshop(r)
      software. Data were analyzed using ANOVA and Tukey tests, at 5% significance
      level. At 0.6 and 1 mm thickness, all the tested materials showed radiopacity
      higher than 3 mm of aluminum (reference value). At 0.3 mm thickness, Odous and
      Tanari presented significantly less radiopacity than the reference, and the other
      materials showed similar radiopacity to the reference. The study concluded that
      the materials demonstrated different radiopacities and all had values above the
      minimum recommended by ANSI/ADA specification #57, being Odous and Tanari less
      radiopaque than the reference value in thinner samples (0.3mm).

PMID- 29215685
TI  - Micro-CT Evaluation of Root and Canal Morphology of Mandibular First Premolars
      with Radicular Grooves.
AB  - The aim of this study was to evaluate morphological features of 70 single-rooted
      mandibular first premolars with radicular grooves (RG) using micro-CT technology.
      Teeth were scanned and evaluated regarding the morphology of the roots and root
      canals as well as length, depth and percentage frequency location of the RG.
      Volume, surface area and Structure Model Index (SMI) of the canals were measured
      for the full root length. Two-dimensional parameters and frequency of canal
      orifices were evaluated at 1, 2, and 3 mm levels from the apical foramen. The
      number of accessory canals, the dentinal thickness, and cross-sectional
      appearance of the canal at different root levels were also recorded. Expression
      of deep grooves was observed in 21.42% of the sample. Mean lengths of root and RG
      were 13.43 mm and 8.5 mm, respectively, while depth of the RG ranged from 0.75 to
      1.13 mm. Mean canal volume, surface area and SMI were 10.78 mm3, 58.51 mm2, and
      2.84, respectively. Apical delta was present in 4.35% of the sample and accessory
      canals were observed mostly at the middle and apical thirds. Two-dimensional
      parameters indicated an oval-shaped cross-sectional appearance of the root canal
      with a high percentage frequency of canal divisions (87.15%). Canal configuration
      type V (58.57%) was the most prevalent. C-shaped configuration was observed in 13
      premolars (18.57%), whereas dentinal thickness ranged from 1.0 to 1.31 mm.
      Radicular grooves in mandibular first premolars was associated with the
      occurrence of several anatomical complexities, including C-shaped canals and
      divisions of the main root canal.

PMID- 29215686
TI  - Are Desensitizing Toothpastes Equally Biocompatible and Effective Against
      Microorganisms?
AB  - The aims of this study were evaluate cytotoxicity, genotoxicity, antimicrobial
      activity of desensitizing toothpastes compared to a common one and the surface
      roughness of tooth enamel submitted to brushing with these toothpastes. Samples
      of three desensitizing toothpastes (Colgate Sensitive, Sensodyne and Oral B
      Sensitive) and common toothpaste (Colgate) were placed in contact with gingival
      human fibroblasts. Cytotoxicity and genotoxocity were measured by MTT assay and
      micronucleus test. Antimicrobial activity of the toothpastes extracts against C.
      albicans, S. mutans and S. aureus were assessed. For surface roughness
      evaluation, bovine teeth were submitted to 10.000 brushing cycles. The results
      were analyzed statically using Mann-Whitney U, ANOVA and Z tests (p<0.05). All
      toothpastes caused cytotoxic effect to the cells (p<0.05), except Colgate
      Sensitive. The toothpastes did not increase the number of micronuclei compared to
      the untreated control group. Colgate eliminated all the evaluated microorganisms
      at lower concentrations compared to Colgate Sensitive and Oral B Sensitive, which
      were not able to eliminate S. aureus. Sensodyne did not reach the minimum
      microbicidal concentration. The surface roughness of tooth enamel increased after
      brushing with Colgate Sensitive and Oral B Sensitive, however the comparison
      between groups showed no difference on the enamel surface roughness presented by
      desensitizing toothpastes when compared with the common one (p>0.05). Based on
      these results, we can conclude that although none toothpaste has induced
      genotoxicity, Colgate Sensitive was also not cytotoxic. Colgate was the most
      effective against the microorganisms, and there were no differences on the enamel
      surface roughness between the groups.

PMID- 29215687
TI  - Impact of Microabrasion on the Effectiveness of Tooth Bleaching.
AB  - The aim of the present study was to evaluate the effect of prior microabrasion on
      the teeth color change and tooth bleaching effectiveness. Eight sound molars were
      mesio-distally sectioned and the halves were randomly allocated to receive enamel
      microabrasion or non-abrasion (control) in one of surfaces (buccal or lingual),
      while the remaining surface received the other treatment. The tooth color on
      baseline was evaluated by spectrophotometer (CieL*a*b system). After the
      microabrasion procedure, the tooth color was measured again. Following, the
      specimens were bleached with 35% hydrogen peroxide for two sessions with one-week
      interval. The color was re-evaluated 7 days after each section and 30 days after
      the second session. The effect of enamel microabrasion on color changes was
      evaluated by paired T-test. Deltas L*, a*, b*, and E were calculated and data
      submitted to 2-way repeated measure ANOVA followed by Tukey's test. Paired T-test
      was also used to assess possible differences on the ultimate color achieved after
      tooth bleaching. Enamel microabrasion reduced the lightness and increased the
      redness of specimens. Specimens that received microabrasion presented higher
      values of ?L* than control after each bleaching procedure; and higher ?a* after
      the 2nd bleaching session. However, the prior enamel microabrasion did not affect
      the ultimate values of color parameters. Despite enamel microabrasion have
      modified the tooth color, this procedure did not affect the ultimate results
      achieved with tooth bleaching using a high-concentrated hydrogen peroxide.

PMID- 29215688
TI  - Microtensile Bond Strength and Microhardness of Composite Resin Restorations
      Using a Sonic-Resin Placement System.
AB  - The aim of this study was to evaluate the efficacy of applying sonic energy on
      microtensile bond strength and microhardness after the restoration process. A
      total of 40 human third molars were extracted. Class II cavities were prepared
      and restored with composite SonicFill or Filtek Z350 XT with and without the
      application of sonic energy. After the teeth were stored in water for 24 h, the
      teeth were sectioned into sticks (1.0 mm2) and subjected to tensile testing. For
      a depth Knoop hardness test, the samples were cut and indentations were made
      sequentially from the surface of the samples to the bottom of the samples in
      three intervals of 1 mm each. The samples were then subjected to a load of 50 g
      for 10 s. The results from the tensile (factors: placement system and composite)
      and hardness (factors: placement system, composite and depth) tests were
      subjected to the Kolmogorov-Smirnov normality test, followed by analysis of
      variance and Tukey's test (5% significance). For the placement system factor,
      higher bond strength was observed for the cavities that were restored with sonic
      energy (p < 0.001). For depth Knoop hardness, the hardness at 1 mm depth was
      significantly greater than that at 3 mm depth just for the restorations with
      Filtek Z350 XT composite without the application of sonic energy. Therefore, the
      use of sonic energy during the restorative process improved bonding, yet it did
      not markedly affect the depth hardness for both composites.

PMID- 29215689
TI  - Influence of Hemostatic Solution on Bond Strength and Physicochemical Properties
      of Resin Cement.
AB  - The aim of this study was to evaluate the degree of conversion, color stability,
      chemical composition, and bond strength of a light-cured resin cement
      contaminated with three different hemostatic solutions. Specimens were prepared
      for the control (uncontaminated resin cement) and experimental groups (resin
      cement contaminated with one of the hemostatic solutions) according to the tests.
      For degree of conversion, DC (n = 5) and color analyses (n = 10), specimens (3 mm
      in diameter and 2 mm thick) were evaluated by Fourier transform infrared
      spectroscopy (FTIR) and CIELAB spectrophotometry (L*, a*, b*), respectively. For
      elemental chemical analysis (n = 1), specimens (2 mm thick and 6 mm in diameter)
      were evaluated by x-ray energy-dispersive spectroscopy (EDS). The bond strengths
      of the groups were assessed by the microshear test (n = 20) in a leucite
      reinforced glass ceramic substrate, followed by failure mode analysis by scanning
      electron microscopy (SEM). The mean values, except for the elemental chemical
      evaluation and failure mode, were evaluated by ANOVA and Tukey's HSD test. The
      color stability was influenced by storage time (p<0.001) and interaction between
      contamination and storage time (p<0.001). Hemostop and Viscostat Clear
      contamination did not affect the DC, however Viscostat increased the DC. Bond
      strength of the resin cement to ceramic was negatively affected by the
      contaminants (p<0.001). Contamination by hemostatic agents affected the bond
      strength, degree of conversion, and color stability of the light-cured resin
      cement tested.

PMID- 29215690
TI  - Impact of Material Shade and Distance from Light Curing Unit Tip on the Depth of
      Polymerization of Composites.
AB  - This study aimed to evaluate the effect of the composite shade and distance from
      the light-curing unit (LCU) tip on the irradiance reaching the bottom of
      composite disks and on the depth of polymerization. Composites of three shades
      (opaque - OXDC, bleach - BXL, and A2) were inserted into molds with 3-mm of
      thickness positioned over a spectrometer and photo-activated with the LCU
      (Bluephase) tip placed at 0 or 1 cm from the composite surface. The mean
      irradiance reaching the bottom of composite was recorded during the entire photo
      activation (30 s). Specimens (2 x 2 x 4 mm) were polymerized and used to map the
      degree of conversion achieved in different depths from irradiated surface.
      Specimens were sectioned into slices that were positioned over the platform of
      the infra-red microscope connected to the spectrometer to map the conversion. The
      conversion was measured in eight different depths every 500-um. Increasing the
      distance of LCU tip reduced the irradiance only for A2. Interposing OXDC disks
      resulted in lowest values of irradiance and A2 the highest one. A tendency to
      decrease the conversion was observed towards the bottom of specimens for all
      experimental conditions, and the slope was more accentuated for OXDC. Differences
      among shades and distances from LCU tip were evident only beyond 1.5-2.0 mm of
      depth. In conclusion, both composite shade and distance from LCU tip might affect
      the light-transmission and depth of polymerization, while the effect of last was
      more pronounced.

PMID- 29215691
TI  - Evaluating Psychometric Properties of an Instrument Addressing Comprehensiveness
      of Care Among Dentists.
AB  - This study aimed to evaluate the psychometric properties of an instrument to
      assess comprehensiveness of care from dentists using a combination of classical
      test theory and item response theory. A 46-item instrument was developed and
      tested by a panel of experts, followed by a pilot test and administration to 187
      primary care dentists in a large Brazilian city. The 46 items were evaluated
      using the following criteria: acceptability, internal consistency, temporal
      stability, inter-item correlation, and tetrachoric correlation. This evaluation
      led to a shortened version consisting of 11 items that met all the criteria
      previously described. The temporal stability was measured using Cohen's kappa,
      and all 11 items presented values greater than 0.5. The Cronbach's alpha value
      was 0.72. None of the 11 items had missing data on the distribution of responses,
      and the model considering the discrimination as varying fit the data better than
      the model considering discrimination as a constant parameter (p<0.001). Item
      characteristic curves showed that 54.5% of items could be considered difficult,
      i.e., only dentists with a good understanding of comprehensiveness responded
      favorably. The 11-item instrument to assess comprehensiveness of care by dentists
      is considered to have good psychometric properties.

PMID- 29215692
TI  - Chondroid Tenosynovial Giant Cell Tumor of the Temporomandibular Joint: A Rare
      Case Report.
AB  - Tenosynovial giant cell tumor of diffuse type (TGCT-d) or pigmented villonodular
      synovitis (PVNS) is a locally aggressive lesion that mostly affects the joints of
      long bones. Chondroid tenosynovial giant cell tumor (CTGCT) or PVNS with
      chondroid metaplasia is a rare distinct subset of synovial tumors that has a
      predilection for the TMJ. We report a rare case of CTGCT in the TMJ, initially
      misdiagnosed as temporomandibular disorder (TMD). A 51-year-old woman was
      referred to the surgeon with the chief complaint of TMJ pain for 5 years and a
      past history of an unsuccessful TMD treatment. Extraoral examination revealed
      discrete preauricular swelling and restricted mandibular range of motion.
      Panoramic radiograph and computerized tomography showed destruction of the
      mandibular fossa and condyle. Histologically, the tumor was composed by large
      mononuclear cells with prominent eosinophilic cytoplasm and grooved nuclei, small
      histiocytoid cells, osteoclast-like multinucleated cells, brown pigmentation and
      areas of chondroid metaplasia. Morphological and immunohistochemical
      characteristics lead to the final diagnosis of CTGCT. The rarity of CTGCT could
      be attributed to the lack of recognition of this lesion, with cases diagnosed as
      chondroblastomas, synovial chodromatosis and chondrosarcoma. The patient received
      immediate reconstruction and recurrence was found 22 months after initial
      intervention. TGCT-d and CTGCT of the TMJ can present similar symptoms to TMD,
      but clinicians must distinguish both lesions by complete examination, imaging
      and, when necessary, histopathologic evaluation.

PMID- 29215693
TI  - Adolescent Depression in Jordan: Symptoms Profile, Gender Differences, and the
      Role of Social Context.
AB  - The influence of gender and other individual and context characteristics on the
      prevalence and severity of depressive symptoms among Jordanian adolescents
      remains unclear. The aims of the current study were to: (a) characterize
      depressive symptoms profiles for Jordanian adolescents; and (b) examine gender
      differences in the type, severity, and correlates of depressive symptoms. Cross
      sectional data were collected from 2,349 Jordanian adolescents ages 12 to 17
      using a nationally representative school survey. The Beck Depression Inventory-II
      was used to assess the presence and severity of depressive symptoms. Female
      adolescents had significantly higher mean depression scores (17.9 [SD = 11.6],
      95% confidence interval [CI] [17.3, 18.5]) than their male counterparts (13.8 [SD
      = 10.2], 95% CI [13.2, 14.5]). Approximately 41% of girls and 26% of boys
      reported scores indicating moderate to severe depression. Sex differences and
      socially constructed gender differences need to be adequately considered in the
      planning and delivery of mental health care for adolescent depression. If the
      risk for depression is gender-specific, prevention strategies cannot be gender
      neutral. [Journal of Psychosocial Nursing and Mental Health Services, 56(2), 44
      55.].

PMID- 29215694
TI  - Strategies to Promote Walking Among Community-Dwelling Individuals With Major
      Mental Disorders.
AB  - Individuals with major mental disorders could benefit from low cost, functional
      ways to support healthy lifestyles. Walking is a popular, preferred, accessible,
      and safe physical activity for many people. Walking is free, requiring no
      specialized equipment or membership fee, and is important to support engagement
      in other daily living activities. The current study explores the benefits of
      walking and strategies for promoting walking among community-dwelling individuals
      with major mental disorders. Key issues include strengthening engagement,
      tracking progress, and sustaining participation to achieve goals related to
      walking. The authors propose ways that nurses can support increased walking
      behavior for improved health and well-being in this population. [Journal of
      Psychosocial Nursing and Mental Health Services, 56(3), 25-32.].

PMID- 29215695
TI  - Identifying Depression in Parents of Children With Autism Spectrum Disorder:
      Recommendations for Professional Practice.
AB  - Parents of children with autism spectrum disorder (ASD) face many challenges, not
      the least of which can be dealing with their own depression. Depression decreases
      an individual's capacity for self-care and is often overlooked in this population
      striving to manage the demands of parenting their child with ASD. This article
      examines current literature related to prevalence, diagnosis, and interventions
      for depression in parents of children with ASD. The review indicates that
      depression is more common in parents of children with ASD than in the general
      public. However, most literature addresses parenting skills rather than
      depression and associated self-care deficits identified in these parents.
      Suggestions for best practice models and proactive interventions to caregivers
      are provided. [Journal of Psychosocial Nursing and Mental Health Services, 56(4),
      23-27.].

PMID- 29215696
TI  - Psychological Capital and Perceived Professional Benefits: Testing the Mediating
      Role of Perceived Nursing Work Environment Among Chinese Nurses.
AB  - The current descriptive cross-sectional study aimed to explore the mediating role
      of perceived nursing work environment (PNWE) in the relationship between
      psychological capital (PsyCap) and perceived professional benefits among Chinese
      nurses. Participants (N = 351) working in two large general hospitals in
      Guangdong, China completed self-report questionnaires from March to May 2017.
      Linear regression analyses and structural equation modeling were performed to
      explore the mediating effect. PsyCap (particularly for hope and optimism) had a
      positive effect on perceived professional benefits, and PNWE was a mediator in
      this relationship among Chinese nurses. A good working environment can be
      regarded as a mediator variable, increasing staff's competence and sense of
      belonging to a team. For successful implementation, nurse managers should use
      effective strategies to increase nurses' confidence and hope while providing a
      comfortable work environment. [Journal of Psychosocial Nursing and Mental Health
      Services, 56(4), 38-47.].

PMID- 29215697
TI  - ARA1 regulates not only l-arabinose but also d-galactose catabolism in
      Trichoderma reesei.
AB  - Trichoderma reesei is used to produce saccharifying enzyme cocktails for
      biofuels. There is limited understanding of the transcription factors (TFs) that
      regulate genes involved in release and catabolism of l-arabinose and d-galactose,
      as the main TF XYR1 is only partially involved. Here, the T. reesei ortholog of
      ARA1 from Pyricularia oryzae that regulates l-arabinose releasing and catabolic
      genes was deleted and characterized by growth profiling and transcriptomics along
      with a xyr1 mutant and xyr1/ara1 double mutant. Our results show that in addition
      to the l-arabinose-related role, T. reesei ARA1 is essential for expression of d
      galactose releasing and catabolic genes, while XYR1 is not involved in this
      process.

PMID- 29215698
TI  - The lncRNA MALAT1 contributes to non-small cell lung cancer development via
      modulating miR-124/STAT3 axis.
AB  - lncRNAs can exert many biological effects in several cancer types. MALAT1 is a
      kind of lncRNA which is greatly overexpressed in several tumors including non
      small cell lung cancer (NSCLC). However, the mechanism of MALAT1 in NSCLC still
      remains unclear. In our current study, we concentrated on the biological
      mechanism of MALAT1 in NSCLC. It was observed that MALAT1 was significantly
      upregulated in five human NSCLC cells including A549, H23, H522, H1299, and H460
      cells compared to normal bronchial epithelial cell line 16HBE cells. On the
      contrary, miR-124 was remarkably downregulated, which indicated a potential
      negative correlation between miR-124 and MALAT1. MALAT1 inhibition can increase
      miR-124 expression in A549 and H460 cells. In addition, miR-124 mimics were able
      to repress MALAT1 expression and miR124 inhibitors can promote MALAT1 levels.
      Then it was found that shMALAT1 can inhibit NSCLC cell proliferation, colony
      formation and apoptosis, which can be reversed by miR-124 inhibitors.
      Bioinformatic analysis predicted the correlation between miR-124 and MALAT1. In
      addition, STAT3 was found to be a novel mRNA target of miR-124. Downregulation of
      MALAT1 can inhibit NSCLC development by enhancing miR-124 and decreasing STAT3
      expression. We speculated that MALAT1can act as a competing endogenous lncRNA
      (ceRNA) to modulate miR-124/STAT3 in NSCLC. Taken these together, we revealed
      that MALAT1/miR-124/STAT3 was involved in NSCLC development.

PMID- 29215699
TI  - LncRNA LINC00880 promotes cell proliferation, migration, and invasion while
      inhibiting apoptosis by targeting CACNG5 through the MAPK signaling pathway in
      spinal cord ependymoma.
AB  - The present study was to investigate the effect of lncRNA LINC00880 targeting
      CACNG5 on cell proliferation, migration, invasion, and apoptosis in spinal cord
      ependymoma (SCE) through the MAPK signaling pathway. GEO database was used to
      download gene expression data related with SCE (GSE50161 and GSE66354) and
      annotation file. LncRNA with differential expression was predicted by Multi
      Experiment Matrix website (MEM). The target gene was analyzed by KEGG pathway
      enrichment analysis. SCE tissues and adjacent tissues were collected. The
      positive expression of CACNG5 protein was tested by immunohistochemistry.
      Expression of LINC00880, CACNG5, and MAPK signaling pathway-related proteins was
      measured with qRT-PCR and Western blotting. Cell proliferation, migration,
      invasion, cycle, and apoptosis were detected using MTT, Transwell assay, Scratch
      test, and Flow cytometry. SCE tissues showed increased LINC00880 expression.
      CACNG5 was a target gene of LINC00880 and correlated with MAPK signaling pathway.
      Compared with adjacent tissues, SCE tissues showed lower positive expression of
      CACNG5. Compared with the blank group, LINC00880 expression was higher in the
      LINC00880 vector and LINC00880 vector + CACNG5 vector groups, and lower in the si
      LINC00880 and si-LINC00880 + si-CACNG5 groups; in the LINC00880 vector and si
      CACNG5 groups, expression of survivin, p38MAPK, ERK1/2, JNK1/2/3 increased and
      CACNG5 and Bax expression reduced, the proliferation, invasion and migration of
      tumor cells increased, and apoptosis rate decreased. Opposite results were found
      in the si-LINC00880 and CACNG5 vector groups. The findings indicate that lncRNA
      LINC00880 targeting CACNG5 inhibits cell apoptosis and promotes proliferation,
      migration, and invasion in SCE through the MAPK signaling pathway.

PMID- 29215700
TI  - Novel smoothened antagonists as anti-neoplastic agents for the treatment of
      osteosarcoma.
AB  - Osteosarcoma (OS) is an ultra-rare highly malignant tumor of the skeletal system
      affecting mainly children and young adults and it is characterized by an
      extremely aggressive clinical course. OS patients are currently treated with
      chemotherapy and complete surgical resection of cancer tissue. However,
      resistance to chemotherapy and the recurrence of disease, as pulmonary
      metastasis, remain the two greatest challenges in the management, and treatment
      of this tumor. For these reasons, it is of primary interest to find alternative
      therapeutic strategies for OS. Dysregulated Hedgehog signalling is involved in
      the development of various types of cancers including OS. It has also been
      implicated in tumor/stromal interaction and cancer stem cell biology, and
      therefore presents a novel therapeutic strategy for cancer treatment. In our
      work, we tested the activity of five potent Smoothened (SMO) inhibitors, four
      acylguanidine and one acylthiourea derivatives, against an OS cell line. We found
      that almost all our compounds were able to inhibit OS cells proliferation and to
      reduce Gli1 protein levels. Our results also indicated that SMO inhibition in OS
      cells by such compounds, induces apoptosis with a nanomolar potency. These
      findings suggest that inactivation of SMO may be a useful approach to the
      treatment of patients with OS.

PMID- 29215701
TI  - Long non-coding RNA (LncRNA) RMST in triple-negative breast cancer (TNBC):
      Expression analysis and biological roles research.
AB  - Microarray showed that lncRNA RMST was differentially expressed in cervical
      cancer. Further experiments were conducted to detect the expression and
      biological function of RMST in triple-negative breast cancer (TNBC). Microarray
      was used to screen the differentially expressed lncRNAs in TNBC. QRT-PCR was
      applied to uncover the expression of RMST in TNBC tissues. The cell viability of
      RMST-transfected TNBC cells were probed by CKK-8 assay and colony formation
      assay. TUNEL assay was conducted to test the cell apoptosis and FCM assay was
      exerted to detect the cell cycle. The invasion and migration ability of
      transfected cells were examined by transwell assay. RMST played its biological
      function through regulating the mRNA or protein expression in cytoplasm. CCK-8
      and colony formation assay unveiled that RMST could slow down the proliferation
      of TNBC cells to influence the tumor progression. TUNEL results revealed that
      RMST could enhance cell apoptosis in TNBC. The cell cycle detected by FCM assay
      indicated that RMST might induce the block of G0/G1 phase thus inhibiting TNBC
      cell proliferation. RMST overexpression could also restrain the invasion and
      migration abilities of TNBC cells. RMST played a role of tumor suppressor in TNBC
      through inhibiting cell proliferation, invasion and migration, enhancing cell
      apoptosis, and regulating cell cycle.

PMID- 29215702
TI  - ADAM17 participates in the protective effect of paeoniflorin on mouse brain
      microvascular endothelial cells.
AB  - Paeoniflorin (PF), the most abundant active ingredient of traditional Chinese
      herbal medicine Paeoniae Radix, has been recognized as a potential
      neuroprotectant due to its remarkable efficacy on mitigating cerebral infarction
      and preventing the neurodegenerative diseases. However, the precise mechanisms of
      PF remain incompletely understood. In this study, we first provided evidence for
      the protective effect of PF on hydrogen peroxide-induced injury on mouse brain
      microvascular endothelial bEnd.3 cells, and for transactivation of the epidermal
      growth factor receptor (EGFR) signal induced by PF, suggesting that EGFR
      transactivation might be involved in the beneficial role of PF. Next, by
      detecting the phosphorylation of a disintegrin and metalloprotease 17 (ADAM17) at
      Thr 735 and performing loss-of-function experiments with the ADAM17 inhibitor and
      ADAM 17-siRNA, we showed that PF-induced transactivation of EGFR and downstream
      ERKs and AKT signaling pathways were dependent on ADAM17. Furthermore, PF-induced
      phosphorylation of ADAM17 and the EGFR transactivation were inhibited by the
      inhibitors of adenosine A1 receptor (A1R) or Src kinase that were applied to
      cells prior to PF treatment, implying the involvement of A1R, and Src in the
      activation of ADAM17. Finally, PF reduced the cell surface level of TNF-receptor
      1 (TNFR1) and increased the content of soluble TNFR1 (sTNFR1) in the culture
      media, indicating that PF might enhance the shedding of sTNFR1. Taken together,
      we conclude that A1R and Src-dependent activation of ADAM17 participates in PF
      induced EGFR transactivation and TNFR1 shedding on mouse brain microvascular
      endothelial cells, which may contributes to the neuroprotective effects of PF.

PMID- 29215703
TI  - Design, synthesis, and characterization of alpha, beta-unsaturated carboxylic
      acid, and its urea based derivatives that explores novel epigenetic modulators in
      human non-small cell lung cancer A549 cell line.
AB  - Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics
      that target the chromatin remodeling through the regulation of histone and non
      histone proteins. These inhibitors directed against histone deacetylase (HDAC)
      enzymes have become an important therapeutic tool in oncology; consequently,
      scientific efforts have fortified the quest for newer and novel HDACi, which
      forces the design of structurally innovative HDACi. Various urea containing
      compounds exhibited admirable anticancer activity. On the basis of these
      observations, we design and synthesize HDAC specific blocker molecules which are
      specifically besieged towards class I, class II, and class IV HDAC isoforms to
      enhance the structural assortment for HDACi. Through docking experiments, we
      identified that the compounds were tightly bound to the isoforms of the HDAC
      enzymes at their receptor regions. These derivatives potently inhibited the
      different isoforms, namely, class I, II, and IV of HDACs, by hyperacetylation of
      lysine residues in A549 cells. The mechanism of apoptosis is evident, regulating
      tumor suppressor genes and proteins, thereby facilitating the activation of the
      death receptor pathway by the tumor necrosis factor (TNF) receptor. These
      derivative facilitated the induction of reactive oxygen species (ROS) generation
      leading to downregulation of Bcl2 , and upregulation of Bax expression, thereby
      dysregulating mitochondrial membrane potential (DeltaPsim ) to release cytochrome
      c, and activation of intrinsic pathway. These compounds downregulate the
      extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK)
      pathway to inhibit cell growth, proliferation, and metastasis through the matrix
      metalloproteinases (MMPs) MMP2 and MMP9 in A549 cells. These results suggest that
      our designed urea based derivatives act as epigenetic targeting agents through
      HDAC inhibition.

PMID- 29215705
TI  - Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal
      transition and motility of breast cancer cells.
AB  - The tumor microenvironment plays an important role in tumor initiation and
      progression. It is well documented that nicotine participates in cigarette
      smoking-related malignancies. Previous studies focused on the effects of nicotine
      on tumor cells; however, the role of the microenvironment in nicotine-mediated
      tumorigenesis is poorly understood. Herein, we investigated the effect and
      molecular mechanism of nicotine on fibroblasts and its contribution to breast
      cancer. We found that nicotine induced the epithelial-mesenchymal transition
      (EMT) of breast cancer cells and promoted activation of fibroblasts.
      Interestingly, conditioned medium from nicotine-activated fibroblasts (Nic-CM)
      had a greater impact on promoting the EMT and migratory capability toward cancer
      cells than did treatment with nicotine alone. Production of connective tissue
      growth factor (CTGF) and transforming growth factor (TGF)-beta by nicotine
      treated fibroblasts was demonstrated to be crucial for promoting the EMT and
      cancer cell migration, and blocking of CTGF and TGF-beta in Nic-CM-suppressed
      tumor motility. Moreover, nicotine induced expressions of CTGF, and TGF-beta in
      fibroblasts as identified through alpha7 nicotinic acetylcholine receptor (nAChR)
      dependent activation of the AKT/TAZ signaling mechanism. Together, our data
      showed for the first time that activation of fibroblasts is largely responsible
      for accelerating smoking-mediated breast cancer progression.

PMID- 29215706
TI  - Map and correlate intracellular calcium response and matrix deposition in
      cartilage under physiological oxygen tensions.
AB  - Face to the limited repair capability of cartilage, we intended to find out
      signaling responsible for its matrix synthesis. Since spontaneous calcium
      response likes a label of cell status, here it was mapped in fresh and 24 hr
      cultured in situ chondrocytes under oxygen tensions of 20%, 5%, and 1% as well as
      mimic hypoxia conditions. The calcium source was traced using ethylene glycol-bis
      (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and thapsigargin (TG)
      to treat cartilage. Their relative matrix of type II collagen (COLL-II) and
      glycosaminoglycan (GAG) were quantified after cultured for 3 and 7 days. We
      disclosed the specific fingerprint of calcium response and matrix deposition
      along the histological zones under various oxygen tensions, from which the
      effects of hyperoxia, normoxia, and hypoxia conditions on as well as the optimal
      oxygen tensions for maintenance of various zones of cartilage or chondrocytes
      were derived and obtained. Our results revealed that cytoplasm calcium was
      conducive to synthesize COLL-II but detrimental to synthesize GAG. These results
      provide correlation in addition to details of intracellular calcium response and
      matrix deposition in in situ cartilage along its histological zones under
      physiological oxygen tensions.

PMID- 29215704
TI  - Cardiovascular biochemical risk factors among women with spontaneous preterm
      delivery.
AB  - OBJECTIVE: To determine whether women delivering preterm have unfavorable
      cardiovascular profiles as compared with women who deliver at term. METHODS: A
      prospective observational cohort study enrolled 165 women with spontaneous
      preterm delivery (sPTD) at 24+0 and 36+6 gestational weeks in three perinatal
      care centers in The Netherlands between August 2012 and August 2014. Total
      cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low
      density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine
      were measured within 24 hours after delivery. Lipids and cardiovascular
      biochemical risk factors were compared between women with sPTD and an external
      comparison group of 30 women with term delivery via analysis of covariance.
      RESULTS: Mean gestational age at delivery was 30.7 +/- 3.6 weeks in the sPTD
      group and 40.3 +/- 1.3 weeks in the reference group. Data were adjusted for body
      mass index, age, and center. As compared with the reference group, total
      cholesterol and LDL-cholesterol levels were lower and glucose levels were higher
      among women with sPTD. CONCLUSION: An association between sPTD and unfavorable
      lipids and cardiovascular biochemical risk factors was not established. The
      higher levels of glucose in the sPTD group might be due to increased insulin
      resistance, which is associated with a higher risk of sPTD.

PMID- 29215707
TI  - The diagnostic and prognostic value of circulating microRNAs in coronary artery
      disease: A novel approach to disease diagnosis of stable CAD and acute coronary
      syndrome.
AB  - Coronary artery disease (CAD) is the most common manifestation of CVD and the
      acute coronary syndrome (ACS) is associated with a substantial morbidity and
      mortality in most populations globally. There are several biomarkers for
      diagnosis of MI. Troponin is routinely used as a biomarker in patients with chest
      pain, but it lacks sensitivity in the first hours of onset of symptoms, and so
      there is still a clinical need for new biomarkers for the diagnosis of CAD
      events. Recent studies have shown that miRNAs are involved in atherosclerotic
      plaque formation and their expression is altered during CAD events. Whilst
      studies have shown that several miRNAs are not superior to troponin in the
      diagnosis of a MI, they may be useful in the early diagnosis and prognosis of
      patients with CAD, however further studies are required. In this review we have
      summarized the recent studies investigating circulating miRNAs as novel
      biomarkers for the early detection of MI, CVD risk stratification and in the
      assessment of the prognosis of patients with ACS.

PMID- 29215709
TI  - The potential role of aquaporin 1 on aristolochic acid I induced epithelial
      mesenchymal transition on HK-2 cells.
AB  - Aristolochic acid I (AA-I), one of the main active components in Aristolochaia
      herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial
      fibrosis is one of the most typical features of AAN. To investigate the mechanism
      of Aristolochic acid I (AA-I) -induced renal epithelial-mesenchymal transition
      (EMT) and determine the role of aquaporin-1 (AQP1) in this process, we
      established an AA-I-induced EMT model in human proximal tubular epithelial cells
      (HK-2 cells). Morphological examination, MTT assay, and Western blot analysis
      were performed. Aquaporin 1 (AQP1) and several EMT-related proteins were
      detected, thereby suggesting the occurrence of AA-I-induced EMT. Two main
      pathways of transforming growth factor-beta (TGF-beta) signaling, namely, Smad
      dependent and Smad-independent signaling pathways, were also detected. The
      results showed that the TGF-beta / Smad-independent signaling pathways (beta
      catenin, Ras-Raf-Erk1/2 signaling pathways) were activated, and AQP1 expression
      was decreased during the AA-I induced EMT on HK-2 cells. With the presence of TGF
      beta1 receptor inhibitor (LY364947) and Erk1/2 inhibitor (PD98059), AQP1
      expression was altered by PD98059, suggested that AQP1 could be adjusted by
      Erk1/2 signaling. Moreover, the inhibitory effect of AA-I on AQP1 was stronger
      than that of TGF-beta1, suggested that AQP1 may be an important target on AAN
      clinical therapy.

PMID- 29215708
TI  - Risk factors for nuchal cord entanglement at delivery.
AB  - OBJECTIVE: To identify nuchal cord risk factors. METHODS: The present case
      control study was carried out between December 2016 and April 2017 at two
      hospitals in Yaounde, Cameroon. Singletons with a nuchal cord at delivery (case
      group) as well as the two neonates without a nuchal cord delivered immediately
      after each case (control group), all in cephalic presentation, were included.
      Undated pregnancies were excluded. The main variables studied were maternal age,
      parity, pregnancy duration at delivery, cord insertion site, cord length,
      delivery weight, and fetal sex. RESULTS: A nuchal cord was present in 121 (6.0%)
      of 2015 singletons. The final analysis included 114 and 228 neonates in the case
      and control groups, respectively, with similar maternal age, parity, pregnancy
      duration, and delivery weight. Significant independent risk factors for nuchal
      cord formation were a cord length of 70 cm or more (adjusted odds ratio [aOR]
      19.10, 95% confidence interval [CI] 8.63-42.04), a pregnancy duration of more
      than 42 weeks (aOR 7.43, 95% CI 1.46-37.21), marginal cord insertion (aOR 2.90,
      95% CI 1.11-9.35), and a male fetus (aOR 2.14, 95% CI 1.16-7.74). CONCLUSION:
      Marginal cord insertion and post-term pregnancy should be added to the list of
      known nuchal cord risk factors.

PMID- 29215710
TI  - Impact of nationwide health insurance coverage for non-invasive prenatal testing.
AB  - OBJECTIVE: To describe the changes in women's choices for prenatal testing after
      the introduction of nationwide health insurance coverage for non-invasive
      prenatal testing (NIPT) in Switzerland. METHODS: The present retrospective study
      reviewed data from all women with singleton pregnancies who presented at the
      prenatal unit of Basel University Hospital, Switzerland, for first-trimester
      screening between July 15, 2014, and December 31, 2015. Women were divided into
      three categories according to their risk for aneuploidy, and the uptake of NIPT
      in the period before and after the introduction of the nationwide coverage for
      NIPT was compared. RESULTS: Overall, 887 women were included in the study: 573
      screens were carried out before (group 1) and 314 after (group 2) the
      introduction of insurance coverage for NIPT. In group 1, 53 (9.2%) had NIPT as
      compared with 72 (22.9%) in group 2. Among women with intermediate risk for
      aneuploidies and basic insurance coverage, NIPT increased by 56% (12/88 [14%] vs
      32/46 [70%]; P<0.001). CONCLUSION: There was a notable increase in the uptake of
      NIPT; uptake was most significant among women with basic health insurance and
      intermediate risk for aneuploidy.

PMID- 29215711
TI  - Triage tools for detecting cervical spine injury in pediatric trauma patients.
AB  - BACKGROUND: Pediatric cervical spine injury (CSI) after blunt trauma is rare.
      Nonetheless, missing these injuries can have severe consequences. To prevent the
      overuse of radiographic imaging, two clinical decision tools have been developed:
      The National Emergency X-Radiography Utilization Study (NEXUS) criteria and the
      Canadian C-spine Rule (CCR). Both tools are proven to be accurate in deciding
      whether or not diagnostic imaging is needed in adults presenting for blunt trauma
      screening at the emergency department. However, little information is known about
      the accuracy of these triage tools in a pediatric population. OBJECTIVES: To
      determine the diagnostic accuracy of the NEXUS criteria and the Canadian C-spine
      Rule in a pediatric population evaluated for CSI following blunt trauma. SEARCH
      METHODS: We searched the following databases to 24 February 2015: CENTRAL,
      MEDLINE, MEDLINE Non-Indexed and In-Process Citations, PubMed, Embase, Science
      Citation Index, ProQuest Dissertations & Theses Database, OpenGrey,
      ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials
      Registry Platform (ICTRP), Cochrane Database of Systematic Reviews, the Database
      of Abstracts of Reviews of Effects, the Health Technology Assessment, and the
      Aggressive Research Intelligence Facility. SELECTION CRITERIA: We included all
      retrospective and prospective studies involving children following blunt trauma
      that evaluated the accuracy of the NEXUS criteria, the Canadian C-spine Rule, or
      both. Plain radiography, computed tomography (CT) or magnetic resonance imaging
      (MRI) of the cervical spine, and follow-up were considered as adequate reference
      standards. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the quality of included studies using the QUADAS-2 checklists. They
      extracted data on study design, patient characteristics, inclusion and exclusion
      criteria, clinical parameters, target condition, reference standard, and the
      diagnostic two-by-two table. We calculated and plotted sensitivity, specificity
      and negative predictive value in ROC space, and constructed forest plots for
      visual examination of variation in test accuracy. MAIN RESULTS: Three cohort
      studies were eligible for analysis, including 3380 patients ; 96 children were
      diagnosed with CSI. One study evaluated the accuracy of the Canadian C-spine Rule
      and the NEXUS criteria, and two studies evaluated the accuracy of the NEXUS
      criteria. The studies were of moderate quality. Due to the small number of
      included studies and the diverse outcomes of those studies, we could not describe
      a pooled estimate for the diagnostic test accuracy. The sensitivity of the NEXUS
      criteria of the individual studies was 0.57 (95% confidence interval (CI) 0.18 to
      0.90), 0.98 (95% CI 0.91 to 1.00) and 1.00 (95% CI 0.88 to 1.00). The specificity
      of the NEXUS criteria was 0.35 (95% CI 0.25 to 0.45), 0.54 (95% CI 0.45 to 0.62)
      and 0.2 (95% CI 0.18 to 0.21). For the Canadian C-spine Rule the sensitivity was
      0.86 (95% CI 0.42 to 1.00) and specificity was 0.15 (95% CI 0.08 to 0.23). Since
      the quantity of the data was small we were not able to investigate heterogeneity.
      AUTHORS' CONCLUSIONS: There are currently few studies assessing the diagnostic
      test accuracy of the NEXUS criteria and CCR in children. At the moment, there is
      not enough evidence to determine the accuracy of the Canadian C-spine Rule to
      detect CSI in pediatric trauma patients following blunt trauma. The confidence
      interval of the sensitivity of the NEXUS criteria between the individual studies
      showed a wide range, with a lower limit varying from 0.18 to 0.91 with a total of
      four false negative test results, meaning that if physicians use the NEXUS
      criteria in children, there is a chance of missing CSI. Since missing CSI could
      have severe consequences with the risk of significant morbidity, we consider that
      the NEXUS criteria are at best a guide to clinical assessment, with current
      evidence not supporting strict or protocolized adoption of the tool into
      pediatric trauma care. Moreover, we have to keep in mind that the sensitivity
      differs among several studies, and individual confidence intervals of these
      studies show a wide range. Our main conclusion is therefore that additional well
      designed studies with large sample sizes are required to better evaluate the
      accuracy of the NEXUS criteria or the Canadian C-spine Rule, or both, in order to
      determine whether they are appropriate triage tools for the clearance of the
      cervical spine in children following blunt trauma.

PMID- 29215712
TI  - Effects of microRNA-10a on synapse remodeling in hippocampal neurons and neuronal
      cell proliferation and apoptosis through the BDNF-TrkB signaling pathway in a rat
      model of Alzheimer's disease.
AB  - The aim of this study was to research the effects of microRNA-10a (miR-10a) on
      synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD)
      through BDNF-TrkB signaling pathway. Rat models of AD were established. The
      neuronal cells were allocated into blank, negative control (NC), miR-10a mimics,
      miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of
      miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and
      tropomyosin receptor kinase B (TrkappaB) were tested using RT-qPCR and Western
      blotting. Neuron cell proliferation, cycle, and apoptosis were observed using
      Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was
      observed under a scanning electron microscope. The miR-10a expression of AD rats
      increased while p38, PSD95, BDNF, CREB, and TrkappaB expression decreased
      compared with the normal rats. Dual luciferase reporter gene assay testified miR
      10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrkappaB
      decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC
      group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with
      cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a
      inhibitors group presented an opposite trend to the miR-10a mimics and K252a
      groups. The synapse was complete and abundant in the miR-10a inhibitors group
      while disappeared in the miR-10a mimics and K252a groups. The results indicated
      that miR-10a restrains synapse remodeling and neuronal cell proliferation while
      promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway.

PMID- 29215713
TI  - Nicotine increases colon cancer cell migration and invasion through epithelial to
      mesenchymal transition (EMT): COX-2 involvement.
AB  - Cigarette smoking is a recognized risk factor for colon cancer and nicotine, the
      principal active component of tobacco, plays a pivotal role in increasing colon
      cancer cell growth and survival. The aim of this study was to determine the
      effect of nicotine on cellular Caco-2 and HCT-8 migration and invasion, focusing
      on epithelial to mesenchymal transition (EMT) induction, and COX-2 pathway
      involvement. In both these cell lines, treatment with nicotine increased COX-2
      expression and the release of its enzymatic product PGE2 . Moreover, nicotine
      stimulated cells showed increased migratory and invasive behavior, mesenchymal
      markers up-regulation and epithelial markers down-regulation, nuclear
      translocation of the beta-catenin, increase of MMP-2 and MMP-9 activity, and
      enhanced NF-kappaB expression. Noticeably, all these effects are largely mediated
      by COX-2 activity, as simultaneous treatment of both cell lines with nicotine and
      NS-398, a selective COX-2 inhibitor, greatly reduced the number of migrating and
      invading cells and reverted nicotine-induced EMT. These findings emphasize that
      nicotine triggers EMT, leading hence to increased migration and invasiveness of
      colon cancer cells. Thereby, the use of COX-2 inhibitor drugs might likely
      counteract nicotine-mediated EMT effects on colon cancer development and
      progression.

PMID- 29215714
TI  - Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4
      loaded hydrogel directs hard tissue bioengineering.
AB  - Photobiomodulation (PBM) therapy displays relevant properties for tissue healing
      and regeneration, which may be of interest for the tissue engineering field.
      Here, we show that PBM is able to improve cell survival and to interact with
      recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate
      odonto/osteogenic differentiation of dental derived mesenchymal stem cells
      (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell
      carrier (Pluronic(r) F-127) loaded with rhBMP4 and then photoactivated. PBM
      improved MSCs self-renewal and survival upon encapsulation in the Pluronic(r) F
      127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was
      premature and markedly improved in the photoactivated MSCs. An in vivo calvarial
      critical sized defect model demonstrated significant increase in bone formation
      after PBM treatment. Finally, a balance in the reactive oxygen species levels may
      be related to the favorable results of PBM and rhBMP4 association. PBM may act in
      synergism with rhBMP4 and is a promise candidate to direct and accelerate hard
      tissue bioengineering.

PMID- 29215715
TI  - HMGB1 contributes to the irradiation-induced endothelial barrier injury through
      receptor for advanced glycation endproducts (RAGE).
AB  - This study aimed to investigate whether HMGB1 (high mobility group box-1 protein)
      and receptor for advanced glycation end products (RAGE) were involved in the
      irradiation-induced endothelial barrier damage and their mechanism. We
      constructed the damage model of endothelium barrier model with bEnd.3 cells. The
      permeability of endothelial barrier was detected by sodium fluorescein (Na-F)
      permeation test, and the irradiation dose which could induce permeability
      transition was determined by being exposed to different irradiation doses (5, 10,
      15, 20 Gy). MTT assay was applied to detect cell viability under different
      concentrations of HMGB1, glycyrrhizic acid (GA, a specific inhibitor of HMGB1),
      and FPS-ZM1 (a blood-brain-barrier permeant blocker of RAGE V domain-mediated
      ligand binding). The expression of HMGB1, RAGE, and related molecules involved in
      MAPK signaling pathway, MMP-2, MMP-9, ZO-1, and claudin 5 of differently treated
      groups were measured by qRT-PCR, western blot, and immunofluorescence. Cells
      possessed stable endothelial barrier function on 4-7 days after seeded on
      transwell plates. The permeability of endothelial barrier would change under at
      least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the
      permeability. After irradiation, the expressions of HMGB1 and RAGE increased and
      MAPK signal pathway was activated. Meanwhile, MMP-2 and MMP-9 were overexpressed,
      while the expression of tight junction proteins ZO-1 and claudin 5 was decreased.
      Radiation could activate MAPK signaling pathway through promoting the expression
      of HMGB1 and RAGE, which further led to endothelial barrier injury and changed
      its permeability.

PMID- 29215716
TI  - Simple kinetic model of mitochondrial swelling in cardiac cells.
AB  - Mitochondria play an important role in both cell survival and cell death. In
      response to oxidative stress, they undergo opening of non-selective permeability
      transition pores (PTP) in the inner mitochondrial membrane. Sustained PTP opening
      triggers mitochondrial swelling due to increased colloidal osmotic pressure in
      the matrix accompanied by mitochondrial membrane depolarization and ATP
      hydrolysis. Mitochondrial swelling is the major factor leading to mitochondria
      mediated cell death through both apoptosis and necrosis. Hence, precise
      estimation of the threshold parameters of the transition of reversible swelling
      to irreversible swelling is important for understanding the mechanisms of PTP
      mediated cell death as well as for the development of new therapeutic approaches
      targeting the mitochondria under pathological conditions. In this study, we
      designed a simple kinetic model of the Ca2+ -induced mitochondrial swelling that
      describes the mechanisms of transition from reversible to irreversible swelling
      in cardiac mitochondria. Values of kinetic parameters calculated using parameter
      estimation techniques that fit experimental data of mitochondrial swelling with
      minimum average differences between the experimental data and model parameters.
      Overall, this study provides a kinetic model verified by data simulation and
      model fitting that adequately describes the dynamics of mitochondrial swelling.

PMID- 29215717
TI  - Nucleoskeletal stiffness regulates stem cell migration and differentiation
      through lamin A/C.
AB  - Stem cell-based tissue engineering provides a prospective strategy to bone tissue
      repair. Bone tissue repair begins at the recruitment and directional movement of
      stem cells, and ultimately achieved on the directional differentiation of stem
      cells. The migration and differentiation of stem cells are regulated by
      nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the
      nucleoskeletal stiffness and consequently to the regulation of cell migration and
      differentiation. Nuclear lamin A/C determines cell migration through the
      regulation of nucleoskeletal stiffness and rigidity and involve in nuclear
      cytoskeletal coupling. Moreover, lamin A/C is the essential core module
      regulating stem cell differentiation. The cells with higher migration ability
      tend to have enhanced differentiation potential, while the optimum amount of
      lamin A/C in migration and differentiation of MSCs is in conflict. This contrary
      phenomenon may be the result of mechanical microenvironment modulation.

PMID- 29215718
TI  - Involvement of Smad3 pathway in atrial fibrosis induced by elevated hydrostatic
      pressure.
AB  - Hypertension is a main risk factor for atrial fibrillation, but the direct
      effects of hydrostatic pressure on the atrial fibrosis are still unknown. The
      present study investigated whether hydrostatic pressure is responsible for atrial
      fibrosis, and addressed a potential role of the Smad pathway in this pathology.
      Biochemical assays were used to study regulation and expression of fibrotic
      factors in spontaneously hypertensive rats (SHRs) and Wistar rats, and in cardiac
      fibroblasts (CFs) cultured under standard (0 mmHg) and elevated (20, 40 mmHg)
      hydrostatic pressure. Levels of atrial fibrosis and protein expression of
      fibrotic factors Col-1A1/-3A1, TGF-beta1, and MMP-2 in SHRs' left atrial tissues
      were higher than those in Wistar rats. Exposure to elevated pressure was
      associated with the proliferation of CFs. The protein expression of Col-1A1/-3A1,
      TGF-beta1, and MMP-2 in CFs was also up-regulated in a pressure-dependent manner.
      The proliferation of CFs and increased expressions of fibrotic markers induced by
      elevated hydrostatic pressure could be reversed by the Smad3 inhibitor
      naringenin. The activation of Smad3 pathway was also stimulated by elevated
      hydrostatic pressure. These results demonstrate that CF secretory function and
      proliferation can be up-regulated by exposure to elevated pressure, and that
      Smad3 may modulate CF activation induced by high hydrostatic pressure.

PMID- 29215719
TI  - Retraction: Wang, L., Ma, X., Yan, L., Wang, T., Wen, J. and Mi, G., LncRNA SNHG1
      negatively regulates miR-145a-5p to enhance NUAK1 expression and promote cancer
      cell metastasis and invasion in nasopharyngeal carcinoma. J Cell Physiol.
      Accepted Author Manuscript. doi:10.1002/jcp.26340.
AB  - The above article from the Journal of Cellular Physiology, published online on 7
      December 2017 in Wiley Online Library (wileyonlinelibrary.com), has been
      withdrawn by agreement between the authors, the journal Editor in Chief, Gary
      Stein, and Wiley Periodicals, Inc. The withdrawal has been agreed due to the
      article being submitted for publication without the consent of the authors'
      instructor.

PMID- 29215720
TI  - GSK3beta regulates ameloblast differentiation via Wnt and TGF-beta pathways.
AB  - Wnt and TGF-beta signaling pathways participate in regulating a variety of cell
      fates during organogenesis, including tooth development. Despite well-documented,
      the specific mechanisms, especially how these two pathways act coordinately in
      regulating enamel development, remain unknown. In this study, we identified
      Glycogen Synthase Kinase 3 beta (GSK3beta), a negative regulator of Wnt signal
      pathway, participated in ameloblast differentiation via Wnt and TGF-beta pathways
      during enamel development. In vitro rat mandible culture treated with specific
      GSK3beta inhibitor SB415286 displayed enamel defects, accompanied by disrupted
      ameloblasts polarization, while odontoblasts and dentin appeared to be
      unaffected. Moreover, after GSK3beta knockdown by lentivirus-mediated RNA
      silencing, HAT-7 cells displayed abnormal cell polarity and cell adhesion, and
      failed to synthesize appreciable amounts of ameloblast-specific proteins. More
      importantly, inactivation of GSK3beta caused upregulated Wnt and downregulated
      TGF-beta pathway, while reactivation of TGF-beta signaling or suppression of Wnt
      signaling partially rescued the differentiation defects of ameloblasts caused by
      the GSK3beta knock-down. Taken together, these results suggested that GSK3beta
      was essential for ameloblasts differentiation, which might be indirectly mediated
      through Wnt and TGF-beta signaling pathways.

PMID- 29215721
TI  - The biological roles and clinical implications of microRNAs in clear cell renal
      cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) accounts for about 3% of tumors in adults
      as well as 85% of all primary renal carcinoma. And it is the third most
      predominant urological carcinoma, but it has the maximum mortality rate. Early
      diagnosis and proper follow-up of ccRCC patients may improve the prognosis of the
      illness. Thus, it is imperative to understand the new biomarkers of ccRCC and
      study new method for the modern therapy of this deadly disease. Furthermore, a
      large number of microRNAs (miRNAs), small non-coding RNAs, have been relevant to
      tumor type, stage, or survival and miRNAs might be progressed as the markers of
      diagnosis or prognosis in ccRCC. A growing body of data also advised the
      rationality of regarding miRNAs as therapeutic targets for ccRCC treatment. In
      this review, we tried to summarize biogenesis of miRNAs and their expression
      profiles, biological roles, and clinical implications in ccRCC.

PMID- 29215722
TI  - FGF-2 promotes osteocyte differentiation through increased E11/podoplanin
      expression.
AB  - E11/podoplanin is critical in the early stages of osteoblast-to-osteocyte
      transitions (osteocytogenesis), however, the upstream events which regulate E11
      expression are unknown. The aim of this study was to examine the effects of FGF-2
      on E11-mediated osteocytogenesis and to reveal the nature of the underlying
      signaling pathways regulating this process. Exposure of MC3T3 osteoblast-like
      cells and murine primary osteoblasts to FGF-2 (10 ng/ml) increased E11 mRNA and
      protein expression (p < 0.05) after 4, 6, and 24 hr. FGF-2 induced changes in E11
      expression were also accompanied by significant (p < 0.01) increases in Phex and
      Dmp1 (osteocyte markers) expression and decreases in Col1a1, Postn, Bglap, and
      Alpl (osteoblast markers) expression. Immunofluorescent microscopy revealed that
      FGF-2 stimulated E11 expression, facilitated the translocation of E11 toward the
      cell membrane, and subsequently promoted the formation of osteocyte-like
      dendrites in MC3T3 and primary osteoblasts. siRNA knock down of E11 expression
      achieved >70% reduction of basal E11 mRNA expression (p < 0.05) and effectively
      abrogated FGF-2-related changes in E11 expression and dendrite formation. FGF-2
      strongly activated the ERK signaling pathway in osteoblast-like cells but
      inhibition of this pathway did not block the ability of FGF-2 to enhance E11
      expression or to promote acquisition of the osteocyte phenotype. The results of
      this study highlight a novel mechanism by which FGF-2 can regulate osteoblast
      differentiation and osteocyte formation. Specifically, the data suggests that FGF
      2 promotes osteocytogenesis through increased E11 expression and further studies
      will identify if this regulatory pathway is essential for bone development and
      maintenance in health and disease.

PMID- 29215723
TI  - High cholesterol in lipid rafts reduces the sensitivity to EGFR-TKI therapy in
      non-small cell lung cancer.
AB  - Overcoming EGFR-TKI resistant which has the initial enthusiasm over substantial
      clinical responses is a formidable challenge on nowadays. In this study, we
      showed that cholesterol level in lipid rafts in gefitinib resistant non-small
      cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib
      sensitive cell line, and depletion of cholesterol increased gefitinib
      sensitivity. Furthermore, cholesterol-depleted enhanced gefitinib inhibit
      phosphorylation of EGFR, Akt-1, MEK1/2, and ERK1/2 and these were reversed in
      cholesterol add-back experiments. Gefitinib resistant cell lines showed high
      affinity of gefitinib and EGFR when cholesterol was depleted. Therefore,
      targeting cholesterol combined with EGFR-TKI is potentially a novel therapeutic
      strategy for gefitinib resistant treatment.

PMID- 29215725
TI  - Prognostic impact of circulating tumor cells in patients with ampullary cancer.
AB  - Circulating tumor cells (CTCs) are an important topic of investigation for both
      basic and clinical cancer research. In this prospective study, we evaluated the
      clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62
      consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy
      controls for their CTC content. Combined data from immunostaining of CD45, 4',6
      diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a
      chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were
      CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was
      used to assess the relationship between CTCs, clinical characteristics, and
      patient outcomes. We detected >=2 CTCs/3.2 ml whole blood in 43 of 62 patients
      (69.4%), as well as >=5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff
      value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a
      diagnostic tool; CTCs were associated with tumor burden. CTC levels >=3/3.2 ml
      (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and
      >=5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with
      shorter disease-free survival. Moreover, >=3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2
      6.3, p = 0.019) and >=5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were
      predictive of shorter overall survival. CTC assessment may help identify patients
      with ampullary cancer who are at high risk of an unfavorable outcome.

PMID- 29215724
TI  - Pericytes modulate myelination in the central nervous system.
AB  - Multiple sclerosis is a highly prevalent chronic demyelinating disease of the
      central nervous system. Remyelination is the major therapeutic goal for this
      disorder. The lack of detailed knowledge about the cellular and molecular
      mechanisms involved in myelination restricts the design of effective treatments.
      A recent study by using [De La Fuente et al. (2017) Cell Reports, 20(8): 1755
      1764] by using state-of-the-art techniques, including pericyte-deficient mice in
      combination with induced demyelination, reveal that pericytes participate in
      central nervous system regeneration. Strikingly, pericytes presence is essential
      for oligodendrocyte progenitors differentiation and myelin formation during
      remyelination in the brain. The emerging knowledge from this research will be
      important for the treatment of multiple sclerosis.

PMID- 29215726
TI  - Sel1l knockdown negatively influences zebrafish embryos endothelium.
AB  - SEL1L (suppressor/enhancer of Lin-12-like) is a highly conserved gene associated
      with the endoplasmic reticulum-associated degradation (ERAD) pathway and involved
      in mediating the balance between stem cells self-renewal and differentiation of
      neural progenitors. It has been recently shown that SEL1L KO mice are embryonic
      lethal and display altered organogenesis. To better characterize the function of
      SEL1L in the early stages of embryonic development, we turned to the zebrafish
      model (Danio rerio). After exploring sel1l expression by RT-PCR and in situ
      hybridization, we employed a morpholino-mediated down-regulation approach.
      Results showed extensive impairments in the vasculature, which supports the mice
      knock-out findings.

PMID- 29215727
TI  - Secreted frizzled-related protein 1 regulates the progression of neuropathic pain
      in mice following spinal nerve ligation.
AB  - Previous studies have shown that the Wnt/beta-catenin signaling pathway plays an
      important role in modulating neuropathic pain after sciatic nerve injury. In this
      study, we explored the role of secreted frizzled-related protein 1 (SFRP1), a Wnt
      antagonist, in neuropathic pain using a mouse model following spinal nerve
      ligation (SNL). We found SNL-induced SFRP1 downregulation in the spinal cord.
      Further, overexpression of SFRP1 via spinal injection into the spinal cord
      attenuated SNL-induced allodynia, hyperalgesia, and neuroinflammation.
      Consistently, in vitro assays also showed decreased expression of SFRP1 in spinal
      cord astrocytes after exposure to lipopolysaccharide (LPS). Overexpression of
      SFRP1 significantly alleviated the secretion of LPS-induced proinflammatory
      factors in spinal cord astrocytes. Furthermore, spinal injection of LPS-treated
      astrocytes induced allodynia and hyperalgesia, which were reversed by the
      overexpression of SFRP1 in these cells. Additionally, SNL increased Wnt3a and
      beta-catenin levels and also induced an increase in nuclear expression of beta
      catenin; these effects were all attenuated by SFRP1. Finally, we found that
      downregulation of SFRP1, mainly through DNA methylation, is involved in the
      pathogenesis of neuropathic pain. Taken together, these results suggested that
      the SFRP1/Wnt3a/beta-catenin signaling pathway might be a suitable therapeutic
      target for neuropathic pain.

PMID- 29215728
TI  - Multiple neuronal pathologies are common in young patients with pathologically
      proven Frontotemporal lobar degeneration.
AB  - AIMS: The past decade has seen a surge in studies identifying mixed pathologies
      in elderly populations. Importantly however, few studies have focussed on mixed
      pathology in Frontotemporal Lobar Degeneration (FTLD), particularly in younger
      cases. METHODS: The present study examined concomitant pathological neuronal
      inclusions of TDP-43, hyperphosphorylated tau and alpha-synuclein protein in the
      anterior cingulate, hippocampus and entorhinal cortex in young (<=65 years at
      death) vs. elderly (>=80 years at death) cases with pathologically confirmed FTLD
      (n = 52) or Alzheimer's disease (AD) (n = 47). RESULTS: Our results demonstrate
      the presence of additional neuronal pathologies not associated with the primary
      pathological diagnosis in a similar proportion of young and elderly FTLD cases,
      indicating that disease drivers rather than age are the major risk factors for
      multiple neuronal pathologies in FTLD. When only sporadic FTLD cases were
      considered, the proportion of cases with multiple neuronal pathologies across
      FTLD age cohorts remained similar, indicating that multiple neuronal pathologies
      in young FTLD cases is not driven by known genetic mutations. In contrast to
      these findings in FTLD, a significantly greater proportion of elderly compared to
      young AD cases demonstrated multiple neuronal pathologies, corroborating
      literature. CONCLUSIONS: In summary, the present study reports for the first time
      that age is not a major risk factor for multiple neuronal pathologies in FTLD.
      These findings have significant implications for the development of protein
      specific biomarkers and treatments for FTLD, and underscore the need for further
      research to identify the disease factors involved in driving multiple neuronal
      pathologies in FTLD.

PMID- 29215729
TI  - Crosstalk between adipose stem cells and tendon cells reveals a temporal
      regulation of tenogenesis by matrix deposition and remodeling.
AB  - Tendon injuries constitute an unmet clinical challenge owing to the limited
      intrinsic regenerative ability of this tissue. Cell-based therapies aim at
      improving tendon healing through the delicate orchestration of tissue rebuilding
      and regain of function. Hence, human adipose-derived stem cells (hASCs) have been
      proposed as a promising cell source for boosting tendon regeneration. In this
      work, we investigated the influence of hASCs on native human tendon-derived cells
      (hTDCs) through the establishment of a direct contact co-culture system. Results
      demonstrated that direct interactions between these cell types resulted in
      controlled proliferation and spontaneous cell elongation. ECM-related genes,
      particularly COL1A1 and TNC, and genes involved in ECM remodeling, such as MMP1,
      MMP2, MMP3, and TIMP1, were expressed in co-culture in a temporally regulated
      manner. In addition, deposition of collagen type I was accelerated in co-culture
      systems and favored over the production of collagen type III, resulting in an
      enhanced COL1/COL3 ratio as soon as 7 days. In conclusion, hASCs seem to be good
      candidates in modulating the behavior of native tendon cells, particularly
      through a balanced process of ECM synthesis and degradation.

PMID- 29215730
TI  - Non-enzymatic antioxidant accumulations in BR-deficient and BR-insensitive barley
      mutants under control and drought conditions.
AB  - Drought is one of the most adverse stresses that affect plant growth and yield.
      Disturbances in metabolic activity resulting from drought cause overproduction of
      reactive oxygen species. It is postulated that brassinosteroids (BRs) regulate
      plant tolerance to the stress conditions, but the underlying mechanisms remain
      largely unknown. An involvement of endogenous BRs in regulation of the
      antioxidant homeostasis is not fully clarified either. Therefore, the aim of this
      study was to elucidate the role of endogenous BRs in regulation of non-enzymatic
      antioxidants in barley (Hordeum vulgare) under control and drought conditions.
      The plant material included the 'Bowman' cultivar and a group of semi-dwarf near
      isogenic lines (NILs), representing mutants deficient in BR biosynthesis or
      signaling. In general, accumulations of 11 compounds representing various types
      of non-enzymatic antioxidants were analyzed under both conditions. The analyses
      of accumulations of reduced and oxidized forms of ascorbate indicated that the BR
      mutants contain significantly higher contents of dehydroascorbic acid under
      drought conditions when compared with the 'Bowman' cultivar. The analysis of
      glutathione accumulation indicated that under the control conditions the BR
      insensitive NILs contained significantly lower concentrations of this antioxidant
      when compared with the rest of genotypes. Therefore, we postulate that BR
      sensitivity is required for normal accumulation of glutathione. A complete
      accumulation profile of various tocopherols indicated that functional BR
      biosynthesis and signaling are required for their normal accumulation under both
      conditions. Results of this study provided an insight into the role of endogenous
      BRs in regulation of the non-enzymatic antioxidant homeostasis.

PMID- 29215731
TI  - Eucalyptol Protects Lungs against Bacterial Invasion through Attenuating Ciliated
      Cell Damage and Suppressing MUC5AC Expression.
AB  - This study was conducted to investigate whether Eucalyptol plays a role in
      influencing bacterial growth in cigarette smoke exposed lungs. Rats were exposed
      to air (control) and cigarette smoke (smoking) in presence and absence of
      Eucalyptol (260 mg/day). Morphological analysis of lung structures and status of
      airway mucous production were observed under a microscope. Pathological changes
      of ciliated columnar epithelium in airways were examined using transmission
      electron microscopy. MUC5AC protein and mRNA expression in bronchoalveolar lavage
      fluid (BALF) and lungs were determined. Application of Eucalyptol reduced
      pulmonary bullae formation and airway mucus overproduction in the smoke exposed
      lungs. Treatment with Eucalyptol attenuated ciliated cell damage in cigarette
      smoke exposed lungs. Bacterial colonies of lungs were obviously lower in the
      Eucalyptol treated rats than that in the smoking rats (P < 0.01). Treatment with
      Eucalyptol reduced the counts of bacterial colonization residing in the
      challenged lungs (P < 0.01). Application of Eucalyptol not only decreased MUC5AC
      protein expression in BALF and tobacco-exposed lungs but also suppressed its mRNA
      expression in the lungs (all P < 0.05). Intervention of Eucalyptol benefits
      elimination of bacterial organisms from tobacco exposed lungs through attenuating
      ciliated cell damage and suppressing MUC5AC expression in the lungs. This article
      is protected by copyright. All rights reserved.

PMID- 29215732
TI  - Silicon affects seed development and leaf macrohair formation in Brachypodium
      distachyon.
AB  - Silicon (Si) has many beneficial effects in plants, especially for the survival
      from biotic and abiotic stresses. However, Si may negatively affect the quality
      of lignocellulosic biomass for bioenergy purposes. Despite many studies, the
      regulation of Si distribution and deposition in plants remains to be fully
      understood. Here, we have identified the Brachypodium distachyon mutant low
      silicon 1 (Bdlsi1-1), with impaired channeling function of the Si influx
      transporter BdLSI1, resulting in a substantial reduction of Si in shoots.
      Bioimaging by laser ablation-inductively coupled plasma-mass spectrometry showed
      that the wild-type plants deposited Si mainly in the bracts, awns and leaf
      macrohairs. The Bdlsi1-1 mutants showed substantial (>90%) reduction of Si in the
      mature shoots. The Bdlsi1-1 leaves had fewer, shorter macrohairs, but the overall
      pattern of Si distribution in bracts and leaf tissues was similar to that in the
      wild-type. The Bdlsi1-1 plants supplied with Si had significantly lower seed
      weights, compared to the wild-type. In low-Si media, the seed weight of wild-type
      plants was similar to that of Bdlsi1-1 mutants supplied with Si, while the Bdlsi1
      1 seed weight decreased further. We conclude that Si deficiency results in
      widespread alterations in leaf surface morphology and seed formation in
      Brachypodium, showing the importance of Si for successful development in grasses.

PMID- 29215733
TI  - Sonic hedgehog signaling mediates resveratrol to improve maturation of pig
      oocytes in vitro and subsequent preimplantation embryo development.
AB  - The beneficial effects of resveratrol on in vitro maturation (IVM) have been
      explained mainly by indirect antioxidant effects and limited information is
      available on the underlying mechanism by which resveratrol acts directly on
      porcine cumulus oocyte complexes (COCs). Recently, several studies reported that
      sonic hedgehog (SHH) signaling mediates resveratrol to exert its biological
      activities. Furthermore, SHH is an important signaling molecule for follicle
      development, oocyte maturation, and embryo development. Therefore, to elucidate
      the relationship between resveratrol and SHH signaling, we designed three groups:
      (i) control; (ii) resveratrol; and (iii) resveratrol with cyclopamine (SHH
      signaling inhibitor). We evaluated the effects of these agents on cumulus
      expansion, oocyte maturation, embryo development after parthenogenetic
      activation, expression levels of mRNAs in cumulus cells, oocytes and blastocysts,
      and protein expression in COCs. Resveratrol significantly increased the
      proportion of COCs exhibiting complete cumulus expansion (degree 4), oocyte
      nuclear maturation, cleavage and blastocyst formation rates and total cell
      numbers, which were blocked in the presence of cyclopamine. At the same time, a
      significant increase in the expression levels of mRNAs related to cumulus
      expansion, oocyte maturation and SHH signaling-related mRNAs and proteins from
      the resveratrol treatment group was also inhibited by simultaneous addition of
      cyclopamine. In conclusion, our results indicate that SHH signaling mediates
      resveratrol to improve porcine cumulus expansion, oocyte maturation, and
      subsequent embryo development.

PMID- 29215734
TI  - Study on mechanism about long noncoding RNA MALAT1 affecting pancreatic cancer by
      regulating Hippo-YAP signaling.
AB  - By investigating the migration and invasion ability in pancreatic cancer, this
      study probed into the lncRNA MALAT1 molecular mechanism on Hippo-YAP signaling.
      The expression of lncRNA MALAT1 in PC tissues and cells was detected by qRT-PCR
      and Western blot. The effect of si-MALAT1 on proliferation was determined by CCK
      8 assay. Cell apoptosis, migration, and invasion were respectively detected by
      flow cytometry assay, wound healing assay, and transwell assay. Western blot and
      immunohistochemistry were successively used for detecting LATS1 and YAP1
      expression in pancreatic cancer tissues. The microarray analysis determined that
      lncRNA MALAT1 in pancreatic cancer was highly expressed. LncRNA MALAT1 presented
      an extremely high expression level in pancreatic cancer tissues and cells. After
      transfected with si-MALAT1, the proliferation of AsPC-1 cells decreased, induce
      apoptosis of AsPC-1 cells, and migration and invasion ability were reduced. The
      tendency of LATS1 expression level was down-regulated and YAP1 show the opposite
      trend in the Hippo-YAP signaling. The in vivo assay was found that the tumor to
      be small in size and volume, and the expression of Ki-67 was decreased. High
      expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and
      migration and invasion ability via influence Hippo-YAP signaling pathway.

PMID- 29215736
TI  - Protective effect of epigenetic silencing of CyclinD1 against spinal cord injury
      using bone marrow-derived mesenchymal stem cells in rats.
AB  - This study focuses on the protective effect of epigenetic silencing of CyclinD1
      against spinal cord injury (SCI) using bone marrow-derived mesenchymal stem cells
      (BMSCs) in rats. Eighty-eight adult female Wistar rats were randomly assigned
      into the sham group, the control group, the si-CyclinD1 + BMSCs group and the
      BMSCs group. CyclinD1 protein and mRNA expressions after siRNA transfection were
      detected by Western blotting and qRT-PCR. The siRNA-CyclinD1 BMSCs were
      transplanted into rats in the si-CyclinD1 + BMSCs group using stereotaxic method
      6 hr after SCI. Hindlimb locomotor performance was determined using inclined
      plane test and Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Expressions
      of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were
      detected by immunohistochemistry. Inclined plane and BBB scores in the control,
      si-CyclinD1 + BMSCs, and BMSCs groups were significantly lower than the sham
      group, but these scores were evidently decreased in the control group and
      increased in the si-CyclinD1 + BMSCs group compared with the BMSCs group. The
      repair degree of spinal cord tissues of rats in the si-CyclinD1 + BMSCs group was
      obvious than the BMSCs group. GFAP and NGF protein expressions were markedly
      decreased in the control, si-CyclinD1 + BMSCs and BMSCs groups when compared with
      the sham group. GFAP- and NGF-positive cells were significantly increased in the
      si-CyclinD1 + BMSCs group while decreased in the control group. Our study
      provides evidence that epigenetic silencing of CyclinD1 using BMSCs might
      accelerate the repair of SCI in rats.

PMID- 29215735
TI  - Vacuolated PAS-positive lymphocytes as an hallmark of Pompe disease and other
      myopathies related to impaired autophagy.
AB  - Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of
      the acid-alpha-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen
      accumulation and autophagy impairment in cardiac and skeletal muscles, but also
      in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and
      specific test is crucial to early identify affected subjects. Number of
      lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72
      consecutive adult patients with hyperckemia and/or muscle weakness, 13
      genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring.
      GAA activity, measured on dried blood spot (DBS) in all patients inversely
      correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive
      lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3
      different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase
      deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD
      offspring. These latter resulted to have all a single GAA mutation but low GAA
      levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the
      autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive
      lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing
      both compound heterozygous and heterozygous GAA carriers. The other myopathies
      with more than 4 PAS-positive lymphocytes appeared to be all related to impaired
      autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes
      formation. Quantification of PAS-positive lymphocytes in blood films is useful to
      identify autophagic vacuolar myopathies and should be routinely used as first
      level test for Pompe disease.

PMID- 29215737
TI  - Nitric oxide as a signaling molecule in brassinosteroid-mediated virus resistance
      to Cucumber mosaic virus in Arabidopsis thaliana.
AB  - Brassinosteroids (BRs) are growth-promoting plant hormones that play a crucial
      role in biotic stress responses. Here, we found that BR treatment increased
      nitric oxide (NO) accumulation, and a significant reduction of virus accumulation
      in Arabidopsis thaliana. However, the plants pre-treated with NO scavenger [2-(4
      carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxyl-3-oxide (PTIO)] or
      nitrate reductase (NR) inhibitor (tungstate) hardly had any NO generation and
      appeared to have the highest viral replication and suffer more damages.
      Furthermore, the antioxidant system and photosystem parameters were up-regulated
      in brassinolide (BL)-treated plants but down regulated in PTIO- or tungstate
      treated plants, suggesting NO may be involved in BRs-induced virus resistance in
      Arabidopsis. Further evidence showed that NIA1 pathway was responsible for BR
      induced NO accumulation in Arabidopsis. These results indicated that NO
      participated in the BRs-induced systemic resistance in Arabidopsis. As BL
      treatment could not increase NO levels in nia1 plants in comparison to nia2
      plants. And nia1 mutant exhibited decreased virus resistance relative to Col-0 or
      nia2 plants after BL treatment. Taken together, our study addressed that NIA1
      mediated NO biosynthesis is involved in BRs-mediated virus resistance in A.
      thaliana.

PMID- 29215738
TI  - Electronic cigarette: A recent update of its toxic effects on humans.
AB  - Electronic cigarettes (e-cigarettes), battery-powered and liquid-vaporizing
      devices, were invented to replace the conventional cigarette (c-cigarette)
      smoking for the sake of reducing the adverse effects on multiple organ systems
      that c-cigarettes have induced. Although some of the identified harmful
      components in e-cigarettes were alleged to be measured in lower quantity than
      those in c-cigarettes, researchers unveiled that the toxic effects of e
      cigarettes should not be understated. This review is sought for an attempt to
      throw light on several typical types of e-cigarette components (tobacco-specific
      nitrosamines, carbonyl compounds, and volatile organic compounds) by revealing
      their possible impacts on human bodies through different action mechanisms
      characterized by alteration of specific biomarkers on cellular and molecular
      levels. In addition, this review is intended to draw the limelight that like c
      cigarettes, e-cigarettes could also be accompanied with toxic effects on whole
      human body, which are especially apparent on respiratory system. From head to
      foot, from physical aspect to chemical aspect, from genotype to phenotype,
      potential alterations will take place upon the intake of the liquid aerosol.

PMID- 29215739
TI  - The acclimatised spinal cord.

PMID- 29215740
TI  - The STAT3/NFIL3 signaling axis-mediated chemotherapy resistance is reversed by
      Raddeanin A via inducing apoptosis in choriocarcinoma cells.
AB  - Chemotherapy resistance is the major issue of choriocarcinoma. Apoptosis always
      is the ultimate outcome of chemotherapeutic drugs, which considered one of the
      reasons of resistance. We investigated the role of STAT3/NFIL3 signaling
      inhibited apoptosis in chemotherapy resistance and whether Raddeanin A (RA) could
      be a new drug to reverse resistance. Established three drug-resistant cell lines
      as JEG-3/MTX, JEG-3/5-FU, and JEG-3/VP16. NFIL3 and STAT3 expression was
      evaluated in the cells. The IC50 value, apoptosis rate and apoptins were observed
      with transfection of siNFIL3, Lenti-OETM-NFIL3, shSTAT3, and Lenti-OETM-STAT3 or
      RA treatment. In addition, the luciferase reporter analysis and co
      immunoprecipitation assays were used to investigate the relation of STAT3 and
      NFIL3. Hyper-activation of STAT3 and NFIL3 expression were observed in three drug
      resistant cell lines. STAT3 enhanced NFIL3 transcriptional activity by binding
      the relative promoter region. Activated STAT3/NFIL3 pathway caused low rate of
      apoptosis which resulted in chemotherapy resistance. RA reduced the resistance
      index of resistant cells and induced caspase 3 dependent apoptosis, meanwhile it
      repressed the STAT3/NFIL3 activation. STAT3/NFIL3 axis-inhibited apoptosis is a
      novel mechanism of chemotherapy resistance in choriocarcinoma. With the
      suppression of STAT3/NFIL3 axis and apoptosis induction, RA is a potential agent
      or lead candidate for improving chemotherapy.

PMID- 29215742
TI  - Effects of small interfering RNA targeting TLR4 on expressions of adipocytokines
      in obstructive sleep apnea hyponea syndrome with hypertension in a rat model.
AB  - We explored the effects of RNA interference-mediated silencing of TLR4 gene on
      expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS)
      with hypertension in a rat model. Systolic blood pressure of caudal artery and
      physiological changes were observed when establishing rat models of OSAS with
      hypertension. Mature rat adipocytes were induced from separated and cultured
      primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and
      negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of
      adipocytes were examined after silenced by siRNA by quantitative real-time
      polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay
      (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes
      were detected. Blood pressure in rat caudal artery was higher in the intermittent
      hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes
      in the former group showed physiological changes, which indicated successful
      establishment of rat models of OSAS with hypertension. Red particles could be
      seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4
      mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in
      the untransfected control group. Rats in the TLR4 siRNA group had significantly
      reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6),
      interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) and such
      adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the
      untransfected control group. RNA interference-mediated silencing of TLR4 gene
      could regulate occurrence and development of OSAS with hypertension in rats by
      downregulating expressions of adipocytokines.

PMID- 29215741
TI  - Analysis of sensitive skin barrier function: basic indicators and sebum
      composition.
AB  - OBJECTIVES: Sensitive skin (SS) is a condition characterised by high reactivity,
      low tolerance, and susceptibility to allergies of the skin. Owing to changes in
      the environment and marketing strategies, as well as the increasing public
      awareness about skin care, attention to skin condition is gradually increasing.
      The aim of this study is to explore the differences in the skin barrier of SS and
      normal skin (NS). METHODS: A questionnaire survey was conducted and basic
      indicators of the skin barrier were analysed. It was found that sebum secretion
      in the SS group was lower than that in the NS group, suggesting that the
      development of SS might be associated with sebum secretion and its specific
      components. Next, an ultra performance liquid chromatography-quadruple time-of
      flight mass spectrometer was used to identify facial sebum components in female
      volunteers. RESULTS: The results showed that the sebum of female volunteers with
      SS had high levels of ceramides, glycerophosphoethanolamines, and
      diacylglycerols, and low levels of glucosylceramides, glycerophosphoserines,
      glycerophosphocholines, and triacylglycerols. CONCLUSION: Analysis of lipid
      functions suggested that the main reason for SS development in women might be a
      barrier dysfunction caused by excessive apoptosis and lack of water. Therefore,
      anti-allergy additives in cosmetic products that could inhibit apoptosis of
      keratinocytes and methods to maintain the stability of water molecules in the
      skin should be further studied.

PMID- 29215743
TI  - Driven exercise in the absence of binge eating: Implications for purging
      disorder.
AB  - OBJECTIVE: Purging disorder (PD) is characterized by recurrent purging without
      objectively large binge-eating episodes. PD has received relatively little
      attention, and questions remain about the clinical significance of "purging" by
      exercise that is driven or compulsive (i.e., as extreme compensatory or weight
      control behavior). The little available research suggests that individuals who
      use exercise as a compensatory behavior might have less eating-disorder
      psychopathology than those who purge by vomiting or laxatives, but those studies
      have had smaller sample sizes, defined PD using low-frequency thresholds, and
      defined exercise without weight-compensatory or driven elements. METHOD:
      Participants (N = 2,017) completed a web-based survey with established measures
      of eating-disorder psychopathology, depression, and physical activity.
      Participants were categorized (regular compensatory driven exercise, PD-E, n =
      297; regular compensatory vomiting/laxatives, PD-VL, n = 59; broadly defined
      anorexia nervosa, AN, n = 20; and no eating-disordered behaviors, NED, n = 1,658)
      and compared. RESULTS: PD-E, PD-VL, and AN had higher eating-disorder
      psychopathology and physical activity than NED but did not significantly differ
      from each other on most domains. PD-VL and AN had higher depression than PD-E,
      which was higher than NED. DISCUSSION: Findings suggest that among participants
      with regularly compensatory behaviors without binge eating, those who use
      exercise alone have similar levels of associated eating-disorder psychopathology
      as those who use vomiting/laxatives, although they have lower depression levels
      and overall frequency of purging. Findings provide further support for the
      clinical significance of PD. Clinicians and researchers should recognize the
      severity of driven exercise as a compensatory behavior, and the need for further
      epidemiological and treatment research.

PMID- 29215744
TI  - Identification of virus-derived siRNAs and their targets in RBSDV-infected rice
      by deep sequencing.
AB  - RNA interference (RNAi) is a conserved mechanism against viruses in plants and
      animals. It is thought to inactivate the viral genome by producing virus-derived
      small interfering RNAs (vsiRNAs). Rice black-streaked dwarf virus (RBSDV) is
      transmitted to plants by the small brown planthopper (Laodelphax striatellus),
      and seriously threatens production of rice in East Asia, particularly Oryza
      sativa japonica subspecies. Through deep sequencing, genome-wide comparisons of
      RBSDV-derived vsiRNAs were made between the japonica variety Nipponbare, and the
      indica variety 9311. Four small RNA libraries were constructed from the leaves
      and shoots of each variety. We found 659,756 unique vsiRNAs in the four samples,
      and only 43,485 reads were commonly shared. The size distributions of vsiRNAs
      were mostly 21- and 22-nt long, and A/U bias (66-68%) existed at the first
      nucleotide of vsiRNAs. Additionally, vsiRNAs were continuously but
      heterogeneously distributed along S1-S10 segments of the RBSDV genome.
      Distribution profiles of vsiRNA hotspots were similar in different hosts and
      tissues, and the 5'- and 3'-terminal regions of S4, S5, and S8 had more hotspots.
      Distribution and abundance of RBSDV vsiRNAs could be useful in designing
      efficient targets for exploiting RNA interference for virus resistance. Degradome
      analysis found 25 and 11 host genes appeared to be targeted by vsiRNAs in 9311
      and Nipponbare. We report for the first time vsiRNAs derived from RBSDV-infected
      rice.

PMID- 29215745
TI  - Impacts of long-term precipitation manipulation on hydraulic architecture and
      xylem anatomy of pinon and juniper in Southwest USA.
AB  - Hydraulic architecture imposes a fundamental control on water transport,
      underpinning plant productivity, and survival. The extent to which hydraulic
      architecture of mature trees acclimates to chronic drought is poorly understood,
      limiting accuracy in predictions of forest responses to future droughts. We
      measured seasonal shoot hydraulic performance for multiple years to assess xylem
      acclimation in mature pinon (Pinus edulis) and juniper (Juniperus monosperma)
      after 3+ years of precipitation manipulation. Our treatments consisted of water
      addition (+20% ambient precipitation), partial precipitation-exclusion (-45%
      ambient precipitation), and exclusion-structure control. Supplemental watering
      elevated leaf water potential, sapwood-area specific hydraulic conductivity, and
      leaf-area specific hydraulic conductivity relative to precipitation exclusion.
      Shifts in allocation of leaf area to sapwood area enhanced differences between
      irrigated and droughted KL in pinon but not juniper. Pinon and juniper achieved
      similar KL under ambient conditions, but juniper matched or outperformed pinon in
      all physiological measurements under both increased and decreased precipitation
      treatments. Embolism vulnerability and xylem anatomy were unaffected by
      treatments in either species. Absence of significant acclimation combined with
      inferior performance for both hydraulic transport and safety suggests pinon has
      greater risk of local extirpation if aridity increases as predicted in the
      southwestern USA.

PMID- 29215746
TI  - Reactive oxygen species and colorectal cancer.
AB  - Colorectal cancer (CRC) has become the fourth leading cause of cancer-related
      death in the worldwide. It is urgent to find more effective therapeutic
      strategies for it. Reactive oxygen species (ROS) play multiple roles in normal
      cellular physiology processes. Thus, a certain level of ROS is essential to keep
      normal cellular function. However, the accumulation of ROS shows dual roles for
      cells, which is mainly dependent on the concentration of ROS, the origin of the
      cancer cell and the activated signaling pathways during tumor progression. In
      general, moderate level of ROS leads to cell damage, DNA mutation and
      inflammation, which promotes the initiation and development of cancer. Excessive
      high level of ROS induces cancer cell death, showing an anti-cancer role. ROS are
      commonly higher in CRC cells than their normal counterpart cells. Therefore, it
      is possible that ROS induce cell death in cancer cells while not affecting the
      normal cells, demonstrating lower side effects. Besides, ROS also play a role in
      tumor microenvironment and drug resistance. These multiple roles of ROS make them
      a promising therapeutic target for cancer. To explore potential ROS-target
      therapies against CRC, it is worth to comprehensively understanding the role of
      ROS in CRC and therapy. In this review, we mainly discuss the strategies of ROS
      in CRC therapy, including direct CRC cell target and indirect tumor environment
      target. In addition, the influences of ROS in drug resistance will also been
      discussed.

PMID- 29215747
TI  - Nanoliposomes as the adjuvant delivery systems in cancer immunotherapy.
AB  - Cancer immunotherapy is one of the commonly used methods in the treatment of
      cancer. The aim of this approach is to strengthen or restore immune function for
      effective diagnosis of aberrant cells antigens. For this reason, cancer specific
      peptides or proteins are used as antigens to induce an immune response capable of
      removing cancer cells. Liposomal formulations are an important carrier system
      frequently used for delivery of antigen because the specific properties of this
      component such as lipid composition, charge, size, encapsulation of antigens, or
      adjuvants can be changed. Among different types of liposomal formulations, the
      use of cationic and pH-sensitive nanoliposomes has been markedly increased for
      liposome-based vaccines. In this review, we describe the properties of
      nanoliposomes as delivery systems for cancer immunotherapy.

PMID- 29215748
TI  - Reliability and validity of the Experiences in Close Relationships Scale-12:
      Attachment dimensions in a clinical sample with eating disorders.
AB  - OBJECTIVE: Attachment insecurity is a potential risk factor for the development
      and maintenance of eating disorders (EDs). To date, there are multiple
      psychometrically sound questionnaires for the evaluation of attachment in both
      clinical and healthy populations, such as the Experience in Close Relationships
      (ECR) scale. Composed by two subscales (i.e., attachment anxiety and avoidance),
      the ECR scale was recently adapted to a shorter, 12-item version (ECR-12).
      However, a validation of the ECR-12 among patients with EDs is still lacking. The
      present study sought to investigate the psychometric properties of the ECR-12,
      when used in a treatment-seeking sample with EDs. METHOD: A total of 1,262
      treatment-seeking patients with various ED diagnoses completed the ECR-12,
      together with a commonly used measure of ED psychopathology (Eating Disorder
      Inventory-2). Subsamples also completed the Attachment Style Questionnaire (n =
      66) or underwent a Day Hospital Program (n = 128). RESULTS: A multigroup
      confirmatory factor analysis indicated that the ECR-12 maintained its two-factor
      structure across the ED diagnostic groups. In addition, the scale demonstrated
      good convergent validity, internal consistency, concurrent, and incremental
      validity. Finally, both ECR-12 subscales demonstrated adequate test-retest
      reliability. DISCUSSION: Our results provide preliminary evidence of the
      psychometric properties of ECR-12 in assessing attachment anxiety and avoidance
      among patients with EDs. This short scale could help clinicians tailor
      interventions for EDs that take into account attachment dimensions.

PMID- 29215749
TI  - Building evidence for the use of descriptive subtypes in youth with avoidant
      restrictive food intake disorder.
AB  - OBJECTIVE: To examine characteristics of patients with Avoidant/Restrictive Food
      Intake Disorder (ARFID) in an effort to identify and describe subtypes of the
      disorder. METHOD: A retrospective chart review was completed for patients aged 8
      17 years assessed over a 17-year period. RESULTS: Seventy-seven patients were
      included in the study, the majority of whom were female (n = 56, 73%). The
      average age of patients was 13.7 years (SD = 2.4 years). Three specific subtypes
      of ARFID (aligning with example presentations outlined in the DSM-5) were
      identified: (a) those with weight loss and/or medical compromise as a consequence
      of apparent lack of interest in eating (n = 30, 39%); (b) restriction arising as
      a result of sensory sensitivity (n = 14, 18%); and (c) restriction based upon
      food avoidance and/or fear of aversive consequences of eating (n = 33, 43%).
      Clinical characteristics of patients varied depending on the assigned subtype.
      DISCUSSION: Our findings highlight the need for further research into the
      relative merit of subtype-assignment in patients with ARFID and whether such
      practice would aid in the recommended treatment. Further research is required to
      understand whether these categories are generalizable and applicable to other
      samples such as young children or adults with ARFID, and how treatment options
      might differ according to subtype.

PMID- 29215750
TI  - Questionnaire-based problematic relationship to eating and food is associated
      with 25 year body mass index trajectories during midlife: The Coronary Artery
      Risk Development In Young Adults (CARDIA) Study.
AB  - OBJECTIVE: Problematic eating behaviors and attitudes are of public health
      concern. Questionnaire-based assessment of these behaviors is important for large
      scale research on eating behaviors. The questionnaire on eating and weight
      patterns-revised (QEWP-R) measures potential problematic behaviors and attitudes
      toward food (including anxieties, compensatory actions, overeating and loss of
      control, dieting, and shape concerns) that in aggregate may indicate diagnosable
      eating disorders. An important question regards the prevalence of these issues
      and their longitudinal associations with body mass index (BMI) in generally
      healthy middle aged adults. METHOD: Based on eight constructs measured on QEWP-R,
      we created a new problematic relationship to eating and food (PREF) scale by
      assigning a point for each construct endorsed. Analyses were conducted in 3,892
      black and white men and women participating in the community-based Coronary
      Artery Risk Development in Young Adults (CARDIA) Study. The QEWP-R was
      administered in CARDIA year 10, when participants were aged 27-41 years. We used
      linear regression to model the relationship of individual constructs and the PREF
      scale to BMI over CARDIA follow-up. RESULTS: Fifty-five percent of participants
      had 1-5 points and 4% had 6-8 points on the PREF scale. Each separate construct
      was positively associated with BMI, except concern about weight and shape.
      Adjusting for age, race, sex, education, and study center, mean BMI at CARDIA
      year 10, the time of PREF assessment, was approximately 1.0-2.5 kg/m2 higher per
      PREF category. CONCLUSION: In middle age, problematic behaviors and attitudes
      toward food were common and associated with higher BMI.

PMID- 29215751
TI  - Proteomic response of the rat liver in differential swimming modes.
AB  - Moderate exercise helps improve competition results, providing a balanced muscle
      tone and biochemical activity, whereas excessive training disrupts the balance
      between training and recovery, causes harm to the organism, and leads to
      overtraining syndrome (OTS). To explore the mechanisms of different protein
      expressions during training and acquisition of immunity, we used proteomic
      analyses to investigate the differences of liver-protein expressions between 2
      swimming modes. Sprague-Dawley rats were randomly divided into control (CT),
      fatigue training (FT), and exhaustive training (ET) groups, and liver tissues
      from each group were subjected to 2-dimensional electrophoresis (2DE). A total of
      4518 protein spots were detected in 9 replicates, and 45 protein spots exhibited
      a >2-fold difference in expression (P < .05), 31 of which was successfully
      identified by mass spectrometry. SERPINA3K expression decreased markedly during 2
      stages from CT -> FT and FT -> ET, while DDT, RHOT1, and RBP4 decreased
      significantly only from CT -> ET but not from the former 2 stages. By contrast,
      KRT8, PCBD1, KRT18, PRDX1, and ACY1A showed significant >2-fold increase in
      expression in either the CT -> FT or FT -> ET stages. Bioinformatic analyses
      showed that among the identified proteins, 30.2%, 54.18%, and 15.62% were
      involved in biological processes, molecular functions, and cell composition,
      respectively. Notably, PCBD1, PRDX1, and PPP1CB were involved in redox processes,
      while PPP1CB was only expressed in the FT group. RGN, PSMB9, and AGT, commonly
      recognized as oxidative stress biomarkers, may involve in regulating homeostasis
      in the locomotor mode and may provide diagnostic criteria for the occurrence and
      prevention of exercise-induced fatigue and OTS.

PMID- 29215752
TI  - Familial tauopathy with P364S MAPT mutation: clinical course, neuropathology and
      ultrastructure of neuronal tau inclusions.
AB  - AIMS: This report presents the clinical course, neuropathology and ultrastructure
      of neuronal tau inclusions of four Slovene relatives with P364S MAPT mutation.
      METHODS: The clinical history of three out of four P364S MAPT mutation carriers
      was taken. After formalin fixation, thorough sampling of the central nervous
      system was followed by paraffin embedding, H&E, Gallyas, Bielschowsky and
      immunostaining with AT8, anti-3R, anti-4R tau, anti-amyloid-beta, anti-TDP43 and
      anti-alpha-synuclein antibodies. The distribution and density of different types
      of neuronal tau inclusions were semiquantitatively assessed. In addition, the
      ultrastructure of neuronal tau inclusions was analysed. RESULTS: Macroscopic
      examination of the brains was unremarkable. Microscopically, neuronal tau
      inclusions of almost all known types were widespread and distributed fairly
      uniformly in all cases. Pick bodies and swollen neurones were found in only one
      family member. Mutant tau was composed of 3R and 4R isoforms, with a slight
      predominance of 3R tau. Composite neuronal tau inclusion (CNTI), found in all
      four relatives, was a hallmark of the P364S MAPT mutation. CNTI showed
      compartmental differences in H&E and Gallyas staining, tau isoforms
      immunolabelling and ultrastructure, displaying fuzzy fibrils in the core and
      paired twisted tubules at the periphery. CONCLUSIONS: P364S MAPT mutation is
      characterized clinically by a variable combination of frontotemporal dementia,
      parkinsonism and motor neurone disease of short duration, and neuropathologically
      by a widespread uniform distribution of all known neuronal tau inclusions in one
      family member. Two-compartment CNTI is a unique characteristic of the P364S MAPT
      mutation.

PMID- 29215753
TI  - Combined annotation-dependent depletion score for BRCA1/2 variants in patients
      with breast and/or ovarian cancer.
AB  - Utility of combined annotation-dependent depletion (CADD) score was recently
      reported to rank pathogenicity as C-scores ranging 1-99 for both confirmed
      deleterious mutation. Using C-scores for BRCA1/2 variants, we tried to constitute
      the classification system for variant of uncertain significance (VUS), which had
      been a major problem of genetic testing for hereditary breast and/or ovarian
      cancer. We analyzed BRCA1/2 genes for 283 patients with breast and/or ovarian
      cancer. The deleterious mutation and missesne mutations, minor variant, and wild
      type of BRCA1 and -2 were 5, 27, 251 and 15, 85, 183, respectively. Meanwhile,
      the variants with C-score >=10 were involved in 19/283 (6.7%) in BRCA1 and 34/283
      (12%) in BRCA2. All deleterious mutations were included in this group. Frequency
      of personal history and family history of ovarian cancer were significantly high,
      and frequency of serous adenocarcinoma of ovary and triple negative breast cancer
      was relatively high in the group with deleterious mutations. Similar findings
      were seen in patients with variants of C-score >=10. According to the C-score and
      population frequency, we could define VUS for 11 patients out of 283 patients
      (3.9 CADD is useful to classify the variant of BRCA1/2 and selecting the patient
      who needs further segregation studies.

PMID- 29215754
TI  - Inhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived
      suppressor cells in head and neck cancer.
AB  - Angiogenesis is an essential event in tumor growth and metastasis, and immune
      system also contributes to the tumor evasion. Emerging evidences have suggested
      the bidirectional link between angiogenesis and immunosuppression. Myeloid
      derived suppressor cell (MDSC) is a kind of immunosuppressive cells and plays an
      important role in this process. However, the actual regulatory mechanisms of
      angiogenesis and MDSCs in head and neck squamous cell carcinoma (HNSCC) were
      unclear. In this study, through analyzing the immunohistochemistry staining of
      human HNSCC tissue microarray, we found that the microvascular density (MVD) was
      significantly increased in HNSCC patients. We also characterized angiogenic
      factors p-STAT3, VEGFA, CK2, and MDSCs marker CD11b in HNSCC tissue array, and
      found the close expression correlation among these markers. To determine the role
      of JAK2/STAT3 pathway in tumor microenvironment of HNSCC, we utilized AG490 (an
      inhibitor of JAK2/STAT3) for further research. Results showed that inhibition of
      JAK2/STAT3 suppressed angiogenesis by decreasing VEGFA and HIF1-alpha both in
      vitro and vivo. Moreover, in HNSCC transgenic mouse model, inhibiting JAK2/STAT3
      not only suppressed angiogenesis but also reduced MDSCs in the tumor
      microenvironment through suppressing VEGFA and CK2. Our findings demonstrated the
      close relationship between angiogenesis and MDSCs in HNSCC, and inhibition of
      JAK2/STAT3 could reduce tumor-induced angiogenesis and decrease MDSCs.

PMID- 29215755
TI  - Apelin/APJ system: A critical regulator of vascular smooth muscle cell.
AB  - APJ, an orphan G protein-coupled receptor, is first identified through homology
      cloning in 1993. Apelin is endogenous ligand of APJ extracted from bovine stomach
      tissue in 1998. Apelin/APJ system is widely expressed in many kinds of cells such
      as endothelial cells, cardiomyocytes, especially vascular smooth muscle cell.
      Vascular smooth muscle cell (VSMC), an integral part of the vascular wall, takes
      part in many normal physiological processes. Our experiment firstly finds that
      apelin/APJ system enhances VSMC proliferation by ERK1/2-cyclin D1 signal pathway.
      Accumulating studies also show that apelin/APJ system plays a pivotal role in
      mediating the function of VSMC. In this paper, we review the exact role of
      apelin/APJ system in VSMC, including induction of proliferation and migration,
      enhance of contraction and relaxation, inhibition of calcification. Furthermore,
      we discuss the role of apelin/APJ system in vascular diseases, such as
      atherosclerosis, hypertension, and chronic kidney disease (CKD) from the point of
      VSMC. Above all, apelin/APJ system is a promising target for managing vascular
      disease.

PMID- 29215756
TI  - Downregulation of regulatory T cell function in patients with delayed fracture
      healing.
AB  - Bone fracture healing is a multistage regenerative process that requires the
      collaboration of various cell types, with approximately 5%-10% of fractures not
      healing properly. Accumulating evidence suggests that dysregulations in the
      immune system are associated with defective healing. In a cohort of 30 bone
      fracture patients between 50 and 62 years of age, 8 patients displayed delayed
      healing. Compared to the 22 normal healing patients, these 8 delayed healing
      patients presented significantly lower frequencies of CD4+ CD25hi Foxp3+
      canonical regulatory T cells immediately following bone fracture and early on
      during the healing process. The CD4+ CD25+/hi T cells from delayed healing
      patients also presented reduced capacity to express transforming growth factor
      beta (TGF-beta), and presented reduced surface expression levels of inhibitory
      molecules, including CTLA-4 and Lag-3, compared to CD4+ CD25+/hi T cells from
      normal healing patients. Moreover, CD4+ CD25+/hi T cells from delayed healing
      patients were less potent in the suppression of CD4+ CD25- autologous
      conventional T cell proliferation, and presented reduced expansion capacity in
      response to interleukin (IL)-2 stimulation. Overall, our results demonstrated
      multiple reductions in regulatory T cell function in delayed healing patients
      that could produce long-lasting consequences in the bone fracture healing
      process.

PMID- 29215757
TI  - Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a
      major determinant of renal sympathetic discharge in conscious Wistar rats.
AB  - NEW FINDINGS: What is the central question of this study? Does chronic reduction
      of neuronally generated nitric oxide in the hypothalamic paraventricular nucleus
      affect the set-point regulation of blood pressure and sympathetic activity
      destined to the kidneys? What is the main finding and its importance? Within the
      hypothalamic paraventricular nucleus, nitric oxide generated by neuronal nitric
      oxide synthase plays a major constitutive role in suppressing long term the
      levels of both ongoing renal sympathetic activity and arterial pressure in
      conscious Wistar rats. This finding unequivocally demonstrates a mechanism by
      which the diencephalon exerts a tonic influence on sympathetic discharge to the
      kidney and may provide the basis for both blood volume and osmolality
      homeostasis. ABSTRACT: The paraventricular nucleus (PVN) of the hypothalamus
      plays a crucial role in cardiovascular and neuroendocrine regulation. Application
      of nitric oxide donors to the PVN stimulates GABAergic transmission, and may
      suppress sympathetic nerve activity (SNA) to lower arterial pressure. However,
      the role of endogenous nitric oxide within the PVN in regulating renal SNA
      chronically remains to be established in conscious animals. To address this, we
      used our previously established lentiviral vectors to knock down neuronal nitric
      oxide synthase (nNOS) selectively in the PVN of conscious Wistar rats. Blood
      pressure and renal SNA were monitored simultaneously and continuously for 21 days
      (n = 14) using radio-telemetry. Renal SNA was normalized to maximal evoked
      discharge and expressed as a percentage change from baseline. The PVN was
      microinjected bilaterally with a neurone-specific tetracycline-controllable
      lentiviral vector, expressing a short hairpin miRNA30 interference system
      targeting nNOS (n = 7) or expressing a mis-sense as control (n = 7). Recordings
      continued for a further 18 days. The vectors also expressed green fluorescent
      protein, and successful expression in the PVN and nNOS knockdown were confirmed
      histologically post hoc. Knockdown of nNOS expression in the PVN resulted in a
      sustained increase in blood pressure (from 95 +/- 2 to 104 +/- 3 mmHg, P < 0.05),
      with robust concurrent sustained activation of renal SNA (>70%, P < 0.05). The
      study reveals a major role for nNOS-derived nitric oxide within the PVN in
      chronic set-point regulation of cardiovascular autonomic activity in the
      conscious, normotensive rat.

PMID- 29215758
TI  - Plin5 deficiency promotes atherosclerosis progression through accelerating
      inflammation, apoptosis and oxidative stress.
AB  - Excessive plasma triglyceride and cholesterol levels promote the progression of
      several prevalent cardiovascular risk factors, including atherosclerosis, which
      is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is
      abundant in tissues with very active lipid catabolism, and is involved in the
      regulation of oxidative stress. Although, in?ammation and oxidative stress play a
      critical role in atherosclerosis development, the underlying mechanisms are
      complex and not completely understood. In the present study, we demonstrated the
      role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null
      (ApoE-/- ) mice. Our results suggested that Plin5 expressions increased in the
      artery tissues of ApoE-/- mice. ApoE/Plin5 double knockout (ApoE-/- Plin5-/- )
      exacerbated severer atherogenesis, accompanied with significantly disturbed
      plasma metabolic profiles, such as elevated triglyceride (TG), total cholesterol
      (TC) and low-density lipoprotein cholesterol (LDLC) levels and reduced high
      density lipoprotein cholesterol (HDLC) contents. ApoE-/- Plin5-/- exhibited
      higher number of inflammatory monocytes and neutrophils, as well as over
      expression of cytokines and chemokines linked with inflammatory response.
      Consistently, IkappaBalpha/nuclear factor kappa B (NF-kappaB) pathway was
      strongly activated in ApoE-/- Plin5-/- . Notably, apoptosis was dramatically
      induced by ApoE-/- Plin5-/- , as evidenced by increased cleavage of Caspase-3 and
      Poly (ADP-ribose) polymerase-2 (PARP-2). In addition, ApoE-/- Plin5-/-
      contributed to oxidative stress generation in the aortic tissues, which was
      linked with the activation of phosphatidylinositol 3-kinase /protein kinase B
      (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) pathways. In vitro,
      oxidized low-density lipoprotein (oxLDL) increased Plin5 expression in RAW264.7
      cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress and lipid
      accumulation, while promotion of Plin5 markedly reduced all the effects induced
      by ox-LDL in cells. These studies strongly supported that Plin5 could be a new
      regulator against atherosclerosis, providing new insights on therapeutic
      solutions. This article is protected by copyright. All rights reserved.

PMID- 29215759
TI  - The two faces of enhanced stroma: Stroma acts as a tumor promoter and a steric
      obstacle.
AB  - In addition to genetic, morphological and biochemical alterations in cells, a key
      feature of the malignant progression of cancer is the stroma, including cancer
      cell motility as well as the emergence of metastases. Our current knowledge with
      regard to the biophysically driven experimental approaches of cancer progression
      indicates that mechanical aberrations are major contributors to the malignant
      progression of cancer. In particular, the mechanical probing of the stroma is of
      great interest. However, the impact of the tumor stroma on cellular motility, and
      hence the metastatic cascade leading to the malignant progression of cancer, is
      controversial as there are two different and opposing effects within the stroma.
      On the one hand, the stroma can promote and enhance the proliferation, survival
      and migration of cancer cells through mechanotransduction processes evoked by
      fiber alignment as a result of increased stroma rigidity. This enables all types
      of cancer to overcome restrictive biological capabilities. On the other hand, as
      a result of its structural constraints, the stroma acts as a steric obstacle for
      cancer cell motility in dense three-dimensional extracellular matrices, when the
      pore size is smaller than the cell's nucleus. The mechanical properties of the
      stroma, such as the tissue matrix stiffness and the entire architectural network
      of the stroma, are the major players in providing the optimal environment for
      cancer cell migration. Thus, biophysical methods determining the mechanical
      properties of the stroma, such as magnetic resonance elastography, are critical
      for the diagnosis and prediction of early cancer stages. Fibrogenesis and cancer
      are tightly connected, as there is an elevated risk of cancer on cystic fibrosis
      or, subsequently, cirrhosis. This also applies to the subsequent metastatic
      process.

PMID- 29215760
TI  - Synergistic Effects of Selenophene and Extended Ladder-Type Donor Units for
      Efficient Polymer Solar Cells.
AB  - Two pairs of polymer donor materials based on indacenodithiophene (IDT) and
      indacenodithieno[3,2-b]thiophene (IDTT) as the donor units are synthesized.
      Thiophene or selenophene is introduced as the pi-bridge units and electron
      deficient fluorine-substituted quinoxaline is used as acceptor unit. Selenophene
      containing polymers PIDT-DFQ-Se and PIDTT-DFQ-Se show redshifted absorption and
      narrower bandgaps. Combined with IDTT donor unit, PIDTT-DFQ-Se shows the highest
      absorption coefficient. Both the IDTT unit and selenophene unit have positive
      effects on the hole mobilities, making PIDTT-DFQ-Se the highest one. The best
      power conversion efficiency of 7.4% is obtained from devices based on PIDTT-DFQ
      Se:[6,6]-phenyl C71 butyric acid methyl ester (PC71 BM) with a Jsc of 12.6 mA cm
      2 , a Voc of 0.89 V, and a fill factor (FF) of 0.66.

PMID- 29215761
TI  - In vivo differentiation of common basal cell carcinoma subtypes by microvascular
      and structural imaging using dynamic optical coherence tomography.
AB  - The subtype of basal cell carcinoma (BCC) influences the choice of treatment.
      Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent
      development of an angiographic version of OCT has extended the application of OCT
      to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This
      study explores D-OCT's ability to differentiate the common BCC subtypes by
      microvascular and structural imaging. Eighty-one patients with 98 BCC lesions,
      consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC)
      and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology
      centres. Blinded evaluations of microvascular and structural features were
      performed, followed by extensive statistical analysis of risk ratio (RR) and
      multiple correspondence analysis. nBCC lesions displayed most characteristic
      structural and vascular features. Serpiginous vessels, branching vessels, vessels
      creating a circumscribed figure and sharply demarcated hyporeflective ovoid
      structures in the dermis were all associated with a higher risk of the subtype
      being nBCC. The presence of highly present lines and dark peripheral borders at
      the margin of ovoid structures was negatively associated with iBCC. Lastly, the
      finding of hyporeflective ovoid structures protruding from epidermis correlated
      with sBCC. We identified various microvascular and structural D-OCT features that
      may aid non-invasive identification of BCC subtypes. This would allow clinicians
      to individualize and optimize BCC treatment as well as aid follow-up of non
      surgical treatment.

PMID- 29215762
TI  - Risk of amphetamine use disorder and mortality among incident users of prescribed
      stimulant medications in the Veterans Administration.
AB  - BACKGROUND AND AIMS: Non-medical use of prescribed stimulant medications is a
      growing concern. This study's aims were to ascertain the demographics of
      stimulant medication users compared with non-users, examine temporal trends of
      stimulant medication use and estimate risk factors for development of amphetamine
      use disorder (AUD) and mortality among new users of stimulant medications.
      DESIGN: Cox proportional hazards regression in a retrospective cohort adjusted by
      baseline covariates. SETTING: United States, national administrative database of
      the Veterans Affairs (VA) health-care system. PARTICIPANTS: Adult incident users
      of stimulant medications (n = 78 829) from fiscal years (FY) 2001 to 2012.
      MEASUREMENTS: Primary outcomes were time-to-event: (1) occurrence of AUD
      diagnosis and (2) death. Baseline covariates included demographic information,
      Food and Drug Administration (FDA)-approved indications for stimulant use,
      substance use disorders (SUD) and depression. FINDINGS: Stimulant users compared
      with non-users were younger, more likely to be non-Hispanic white and female.
      Incident stimulant medication users increased threefold from FY2001-FY2012 and
      eightfold among adults aged 18-44 years. Nearly one in 10 incident users in
      FY2012 had a comorbid baseline SUD. Off-label use was common-nearly three of
      every five incident users in FY2012. Comorbid SUDs among incident stimulant
      medication users were risk factors for occurrence of AUD during follow-up, with
      adjusted hazard ratio (AHR) estimates ranging from 1.54 to 2.83 (Ps < 0.05).
      Increased mortality risk was observed with occurrence of AUD during follow-up
      [AHR = 1.55, 95% confidence interval (CI) = 1.13-2.14, P = 0.007], while on-label
      prescribing was protective against death (AHR = 0.686, 95% CI = 0.63-0.75, P <
      0.0001). CONCLUSIONS: In a US national cohort of adult incident stimulant
      medication users in the Veterans Affairs health-care system, measured from fiscal
      years 2001 to 2012, comorbid substance use disorders were common and were risk
      factors for development of an amphetamine use disorder (AUD). Increased mortality
      risk among incident users of stimulant medications was observed among both those
      who developed an AUD later and those whose use was defined as off-label.

PMID- 29215763
TI  - Breast cancer: The translation of big genomic data to cancer precision medicine.
AB  - Cancer is a complex genetic disease that develops from the accumulation of
      genomic alterations in which germline variations predispose individuals to cancer
      and somatic alterations initiate and trigger the progression of cancer. For the
      past 2 decades, genomic research has advanced remarkably, evolving from single
      gene to whole-genome screening by using genome-wide association study and next
      generation sequencing that contributes to big genomic data. International
      collaborative efforts have contributed to curating these data to identify
      clinically significant alterations that could be used in clinical settings.
      Focusing on breast cancer, the present review summarizes the identification of
      genomic alterations with high-throughput screening as well as the use of genomic
      information in clinical trials that match cancer patients to therapies, which
      further leads to cancer precision medicine. Furthermore, cancer screening and
      monitoring were enhanced greatly by the use of liquid biopsies. With the growing
      data complexity and size, there is much anticipation in exploiting deep machine
      learning and artificial intelligence to curate integrative "-omics" data to
      refine the current medical practice to be applied in the near future.

PMID- 29215764
TI  - An evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing
      methodologies for clinical practice.
AB  - Ovarian cancer patients with germline or somatic pathogenic variants benefit from
      treatment with poly ADP ribose polymerase (PARP) inhibitors. Tumor BRCA1/2
      testing is more challenging than germline testing as the majority of samples are
      formalin-fixed paraffin embedded (FFPE), the tumor genome is complex, and the
      allelic fraction of somatic variants can be low. We collaborated with 10
      laboratories testing BRCA1/2 in tumors to compare different approaches to
      identify clinically important variants within FFPE tumor DNA samples. This was
      not a proficiency study but an inter-laboratory comparison to identify common
      issues. Each laboratory received the same tumor DNA samples ranging in genotype,
      quantity, quality, and variant allele frequency (VAF). Each laboratory performed
      their preferred next-generation sequencing method to report on the variants. No
      false positive results were reported in this small study and the majority of
      methods detected the low VAF variants. A number of variants were not detected due
      to the bioinformatics analysis, variant classification, or insufficient DNA. The
      use of hybridization capture or short amplicon methods are recommended based on a
      bioinformatic assessment of the data. The study highlights the importance of
      establishing standards and standardization for tBRCA testing particularly when
      the test results dictate clinical decisions regarding life extending therapies.

PMID- 29215766
TI  - Responses of terrestrial nitrogen pools and dynamics to different patterns of
      freeze-thaw cycle: A meta-analysis.
AB  - Altered freeze-thaw cycle (FTC) patterns due to global climate change may affect
      nitrogen (N) cycling in terrestrial ecosystems. However, the general responses of
      soil N pools and fluxes to different FTC patterns are still poorly understood.
      Here, we compiled data of 1519 observations from 63 studies and conducted a meta
      analysis of the responses of 17 variables involved in terrestrial N pools and
      fluxes to FTC. Results showed that under FTC treatment, soil NH4+ , NO3- , NO3-
      leaching, and N2 O emission significantly increased by 18.5%, 18.3%, 66.9%, and
      144.9%, respectively; and soil total N (TN) and microbial biomass N (MBN)
      significantly decreased by 26.2% and 4.7%, respectively; while net N
      mineralization or nitrification rates did not change. Temperate and cropland
      ecosystems with relatively high soil nutrient contents were more responsive to
      FTC than alpine and arctic tundra ecosystems with rapid microbial acclimation.
      Therefore, altered FTC patterns (such as increased duration of FTC, temperature
      of freeze, amplitude of freeze, and frequency of FTC) due to global climate
      warming would enhance the release of inorganic N and the losses of N via leaching
      and N2 O emissions. Results of this meta-analysis help better understand the
      responses of N cycling to FTC and the relationships between FTC patterns and N
      pools and N fluxes.

PMID- 29215765
TI  - Helicobacter pylori induces caudal-type homeobox protein 2 and cyclooxygenase 2
      expression by modulating microRNAs in esophageal epithelial cells.
AB  - Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of
      Helicobacter pylori. The role of H. pylori in esophageal disease has not been
      clearly defined. We previously reported that H. pylori esophageal colonization
      promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in
      vivo. Here, we studied the direct effects of H. pylori on the transformation of
      esophageal epithelial cells, with particular focus on whether H. pylori exerts
      its effects by modulating miRNAs and their downstream target genes. The normal
      human esophageal cell line HET-1A was chronically exposed to H. pylori extract
      and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the
      esophageal epithelial cells associated with H. pylori infection were determined
      by microarray analysis. We found that chronic H. pylori exposure promoted
      acidified deoxycholic acid-induced morphological changes in HET-1A cells, along
      with aberrant overexpression of intestinal metaplasia markers and tumorigenic
      factors, including caudal-type homeobox protein 2 (CDX2), mucin 2, and
      cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of
      esophageal epithelial cells, particularly aberrant silencing of miR-212-3p and
      miR-361-3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal
      H. pylori colonization was associated with a significant decrease in miR-212-3p
      and miR-361-3p expression. Furthermore, we identified COX2 as a target of miR-212
      3p, and CDX2 as a target of miR-361-3p. Helicobacter pylori infection of
      esophageal epithelial cells was associated with miRNA-mediated upregulation of
      oncoprotein CDX2 and COX2. Our observations provide new evidence about the
      molecular mechanisms underlying the association between H. pylori infection and
      esophageal carcinogenesis.

PMID- 29215767
TI  - Exposure to levonorgestrel increases nest acquisition success and decreases sperm
      motility in the male fathead minnow (Pimephales promelas).
AB  - Progestins are utilized as a component of human contraceptives, and commonly
      enter the environment via wastewater treatment plant effluent. Certain progestins
      activate fish androgen receptors and cause decreases in fecundity and
      masculinization of females. We used a nest acquisition assay and computer
      assisted sperm analysis to examine the effects of levonorgestrel on male fathead
      minnow (Pimephales promelas) reproductive fitness. Males were exposed to 0, 10,
      or 100 ng/L levonorgestrel for 14 d. Combinations of a control male and a male
      from one of the treatments were placed into a competitive nesting assay, and the
      time each male spent holding the nest and time spent exhibiting aggressive
      behaviors were analyzed at 48 h postexposure. Semen samples were analyzed for
      total motility, straight-line velocity, curvilinear velocity, average path
      velocity, linearity, beat cross frequency, and wobble at 0, 30, 60, 90, and 120 s
      postactivation. Males exposed to either 10 or 100 ng/L of levonorgestrel
      exhibited increased nest acquisition success and lower levels of aggression
      compared with control-control pairings, as well as decreases in multiple sperm
      motion characteristics. Our results suggest that further research is required to
      ascertain the effects of levonorgestrel on male gamete quality and reproductive
      behaviors. Environ Toxicol Chem 2018;37:1131-1137. (c) 2017 SETAC.

PMID- 29215768
TI  - From a Metastable Layer to a Stable Ring: A Kinetic Study for Transformation
      Reactions of Li2 Mo3 TeO12 to Polyoxometalates.
AB  - A metastable tellurite, Li2 Mo3 TeO12 , revealing a corrugated layered structure
      in an extremely strained coordination environment was hydrothermally synthesized
      in high yield. Li2 Mo3 TeO12 undergoes Li+ -exchange-driven facile structural
      transformation reactions to polyoxometalates. The kinetic data for the
      transformation reactions at various conditions were successfully obtained by
      simple lab-source powder X-ray diffraction. The investigation suggests that the
      solid-state transformation reactions may occur through a series of steps;
      substitution, decomposition, recombination, and precipitation. This new finding
      could be utilized in discovering functional metastable materials as well as
      understanding their phase transition mechanisms.

PMID- 29215769
TI  - Can a cognitive rehabilitation program in early stages of Parkinson's disease
      improve cognition, apathy and brain functional connectivity for up to 18 months?

PMID- 29215770
TI  - Molecular ecology of Listeria spp., Salmonella, Escherichia coli O157:H7 and non
      O157 Shiga toxin-producing E. coli in pristine natural environments in Northern
      Colorado.
AB  - AIMS: Molecular subtyping is commonly used in foodborne disease surveillance and
      microbial source tracking. There is a knowledge gap regarding the molecular
      ecology of foodborne pathogens in non-food-associated environments. The objective
      of this study was to isolate and subtype foodborne pathogens from pristine
      natural environments with minimal anthropogenic inputs. MATERIALS AND RESULTS:
      Five locations (wilderness areas) in Northern Colorado were sampled during the
      spring, summer and fall over a 2-year period. Soil, water, sediment, surface soil
      and wildlife faecal samples were microbiologically analysed to detect Listeria,
      Salmonella and Shiga toxin-producing Escherichia coli (STEC), and resultant
      isolates were subtyped. Three samples tested positive for Listeria monocytogenes
      and 19 samples contained other Listeria spp. Salmonella was isolated from two
      samples, five samples contained non-O157 STEC, and E. coli O157:H7 was not
      detected. Two L. monocytogenes isolates from faecal samples collected from the
      same wilderness area over a year apart shared the same PFGE pattern, while all
      other isolates had a unique type. CONCLUSIONS: Our data indicate that (i) there
      was a rare presence of human foodborne pathogens in pristine natural environments
      in Northern Colorado, (ii) there was genetic diversity between organisms isolated
      within a given wilderness area, and (iii) the Northern Colorado climate and
      topography may contribute to the low occurrence of these organisms. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Relatively little is known about the molecular ecology
      of foodborne pathogens in pristine natural environments. While foodborne
      pathogens were rarely detected in wildlife faecal and environmental samples from
      the wilderness areas in this study, some isolates shared DNA fingerprint types
      with human clinical isolates from same region during the same time frame,
      highlighting the need for environmental isolate subtype data. The availability of
      molecular subtyping data for non-food-associated foodborne pathogen isolates can
      facilitate epidemiological and microbial source tracking investigations.

PMID- 29215771
TI  - P16 positivity and regression grade predict survival after neoadjuvant
      radiotherapy of OSCC.
AB  - OBJECTIVES: Survival after preoperative radiotherapy in locally advanced head and
      neck squamous cell cancer is associated with pathological response. The
      prognostic importance of p16 expression in these patients has not been
      established yet. MATERIALS AND METHODS: Ninety-seven patients with oral squamous
      cell carcinoma, treated preoperatively with radiotherapy in combination with
      chemotherapy or cetuximab, were included in this retrospective analysis. Survival
      rates were estimated by the Kaplan-Meyer method. Pathological response was
      evaluated by histological analysis and p16 expression by immunohistochemistry.
      RESULTS: Overall survival after 2 years was 66% for the entire group, 92% in the
      p16-positive and 62% in the p16-negative group, respectively. 12.4% of the
      tumours were p16-positive. P16 expression (HR 6.98, p = .05) and regression grade
      (HR 2.94, p = .001) had a statistically significant impact on prognosis. 83.3% of
      p16-expressing tumours were pathological responders. All p16-positive patients
      with pathological response were alive within the observation period. CONCLUSION:
      P16 expression is associated with prognosis in preoperatively irradiated OSCC
      patients. The association between p16 positivity, regression grade and improved
      survival provides a rationale for de-intensification strategies in patients with
      head and neck cancer who respond well to neoadjuvant therapy, a concept that is
      being tested in prospective clinical trials.

PMID- 29215772
TI  - Impact of storage conditions on fungal community composition of green coffee
      beans Coffea arabica L. stored in jute sacks during 1 year.
AB  - AIMS: The purpose of this study was to evaluate the effect of warehouse storage
      conditions on the composition of the fungal community of green coffee beans (GCB)
      that were stored in jute sacks for 1 year. METHODS AND RESULTS: Molecular
      characterization of the fungal community composition and population dynamics
      obtained by Q-PCR, CE-SSCP (Simpson's diversity index D) and Illumina MiSeq
      sequencing indicated that Saccharomycetales dominated during the first 6 months
      of storage period with species as Meyerozyma guilliermondii and Pichia kluyveri.
      However, after 6 months of storage, the filamentous genus Wallemia became
      dominant. Principal components analysis correlated this fungal dynamic with
      storage conditions and other variables as chromaticity (colour), water activity,
      moisture content, reducing sugars concentration, fungal infection and ochratoxin
      A production. CONCLUSIONS: This study demonstrated that GCB stored in jute sacks
      after 6 months of storage lead to fungal population dynamics, decreased
      chromaticity in GCB by bleaching and, then, affected overall quality.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Storage plays an important role in the
      quality evolution during the handling of the GCB. In this context, the
      composition of the microbial community could be considered a marker to assess the
      trade value of the coffee beans.

PMID- 29215773
TI  - A referenceless Nyquist ghost correction workflow for echo planar imaging of
      hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate.
AB  - Single-shot echo planar imaging (EPI), which allows an image to be acquired using
      a single excitation pulse, is used widely for imaging the metabolism of
      hyperpolarized 13 C-labelled metabolites in vivo as the technique is rapid and
      minimizes the depletion of the hyperpolarized signal. However, EPI suffers from
      Nyquist ghosting, which normally is corrected for by acquiring a reference scan.
      In a dynamic acquisition of a series of images, this results in the sacrifice of
      a time point if the reference scan involves a full readout train with no phase
      encoding. This time penalty is negligible if an integrated navigator echo is
      used, but at the cost of a lower signal-to-noise ratio (SNR) as a result of
      prolonged T2 * decay. We describe here a workflow for hyperpolarized 13 C EPI
      that requires no reference scan. This involves the selection of a ghost
      containing background from a 13 C image of a single metabolite at a single time
      point, the identification of phase correction coefficients that minimize signal
      in the selected area, and the application of these coefficients to images
      acquired at all time points and from all metabolites. The workflow was compared
      in phantom experiments with phase correction using a 13 C reference scan, and
      yielded similar results in situations with a regular field of view (FOV), a
      restricted FOV and where there were multiple signal sources. When compared with
      alternative phase correction methods, the workflow showed an SNR benefit relative
      to integrated 13 C reference echoes (>15%) or better ghost removal relative to a
      1 H reference scan. The residual ghosting in a slightly de-shimmed B0 field was
      1.6% using the proposed workflow and 3.8% using a 1 H reference scan. The
      workflow was implemented with a series of dynamically acquired hyperpolarized [1
      13 C]pyruvate and [1-13 C]lactate images in vivo, resulting in images with no
      observable ghosting and which were quantitatively similar to images corrected
      using a 13 C reference scan.

PMID- 29215774
TI  - Photochemical Creation of Fluorescent Quantum Defects in Semiconducting Carbon
      Nanotube Hosts.
AB  - Quantum defects are an emerging class of synthetic single-photon emitters that
      hold vast potential for near-infrared imaging, chemical sensing, materials
      engineering, and quantum information processing. Herein, we show that it is
      possible to optically direct the synthetic creation of molecularly tunable
      fluorescent quantum defects in semiconducting single-walled carbon nanotube hosts
      through photochemical reactions. By exciting the host semiconductor with light
      that resonates with its electronic transition, we find that halide-containing
      aryl groups can covalently bond to the sp2 carbon lattice. The introduced quantum
      defects generate bright photoluminescence that allows tracking of the reaction
      progress in situ. We show that the reaction is independent of temperature but
      correlates strongly with the photon energy used to drive the reaction, suggesting
      a photochemical mechanism rather than photothermal effects. This type of
      photochemical reactions opens the possibility to control the synthesis of
      fluorescent quantum defects using light and may enable lithographic patterning of
      quantum emitters with electronic and molecular precision.

PMID- 29215775
TI  - An assessment of the microbiological quality and safety of raw drinking milk on
      retail sale in England.
AB  - AIMS: This study aimed to review the microbiological results for raw drinking
      milk (RDM) samples submitted to Public Health England laboratories between 2014
      and 2016 in order to produce up-to-date data on the microbiological safety of RDM
      and inform future risk assessments on its sale. METHODS AND RESULTS: A total of
      902 samples of RDM were collected from retail sale in England for microbiological
      examination. Overall, 454 of 770 samples (59.0%) taken for routine monitoring
      were of a satisfactory quality, whilst eight (1.0%) were 'unsatisfactory and
      potentially injurious to health' due to the presence of Shiga toxin-producing
      Escherichia coli, Campylobacter or elevated levels of Listeria monocytogenes or
      coagulase-positive staphylococci. In contrast, 16 of 114 (14.0%) of samples taken
      in follow-up to a previous unsatisfactory result and 5 of 18 (27.8%) of samples
      related to illness were potentially injurious. A total of 229 of 902 samples
      (25.4%) gave unsatisfactory results due to elevated aerobic colony counts and/or
      coliforms, whilst 139 of 902 samples (15.4%) were of borderline quality due to
      coagulase-positive staphylococci. Listeria monocytogenes was detected at levels
      of <100 CFU per ml in 66 of 902 samples (7.3%) and other Listeria species in 44
      of 902 samples (4.9%). CONCLUSIONS: Pathogens and/or indicators of poor hygiene
      were present in almost half of samples examined. Cows' milk samples gave a
      significantly greater proportion of unsatisfactory results compared to milk from
      other species (i.e. goat, sheep, buffalo, camel). SIGNIFICANCE AND IMPACT OF THE
      STUDY: These results demonstrate the importance of maintaining strict controls on
      the production and sale of this product.

PMID- 29215776
TI  - TGF-beta transactivates EGFR and facilitates breast cancer migration and invasion
      through canonical Smad3 and ERK/Sp1 signaling pathways.
AB  - Transforming growth factor-beta (TGF-beta) functions as a potent proliferation
      inhibitor and apoptosis inducer in the early stages of breast cancer, yet
      promotes cancer aggressiveness in the advanced stages. The dual effect of TGF
      beta on cancer development is known as TGF-beta paradox, and the remarkable
      functional conversion of TGF-beta is a pivotal and controversial phenomenon that
      has been widely investigated for decades. This phenomenon may be attributed to
      the cross talk between TGF-beta signaling and other pathways, including EGF
      receptor (EGFR) signaling during cancer progression. However, the underlying
      mechanism by which TGF-beta shifts its role from a tumor suppressor to a cancer
      promoter remains elusive. In this study, TGF-beta is positively correlated with
      EGFR expression in breast cancer tissues, and a functional linkage is observed
      between TGF-beta signaling and EGFR transactivation in breast cancer cell lines.
      TGF-beta promotes the migration and invasion abilities of breast cancer cells,
      along with the increase in EGFR expression. EGFR is also essential for TGF-beta
      induced enhancement of these abilities of breast cancer cells. Canonical Smad3
      signaling and ERK/Sp1 signaling pathways mediate TGF-beta-induced EGFR
      upregulation. Hence, our study provided insights into a novel mechanism by which
      TGF-beta supports breast cancer progression.

PMID- 29215777
TI  - Atypical anorexia nervosa is not related to brain structural changes in newly
      diagnosed adolescent patients.
AB  - OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features
      overlapping with AN in terms of genetic risk, age of onset, psychopathology and
      prognosis of outcome, although the weight loss may not be a core factor. While
      brain structural alterations have been reported in AN, there are currently no
      data regarding atypical AN patients. METHOD: We investigated brain structure
      through a voxel-based morphometry analysis in 22 adolescent females newly
      diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED
      related psychopathology, impulsiveness and obsessive-compulsive traits were
      assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt
      Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R),
      respectively. Body mass index (BMI) was also calculated. RESULTS: Patients and HC
      differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R
      total score (p < .000). No differences could be detected in grey matter (GM)
      regional volume between groups. DISCUSSION: The ED-related cognitions in atypical
      AN patients would suggest that atypical AN and AN could be part of the same
      spectrum of restrictive-ED. However, contrary to previous reports in AN, our
      atypical AN patients did not show any GM volume reduction. The different degree
      of weight loss might play a role in determining such discrepancy. Alternatively,
      the preservation of GM volume might indeed differentiate atypical AN from AN.

PMID- 29215778
TI  - Declines in moth populations stress the need for conserving dark nights.
AB  - Given the global continuous rise, artificial light at night is often considered a
      driving force behind moth population declines. Although negative effects on
      individuals have been shown, there is no evidence for effects on population sizes
      to date. Therefore, we compared population trends of Dutch macromoth fauna over
      the period 1985-2015 between moth species that differ in phototaxis and adult
      circadian rhythm. We found that moth species that show positive phototaxis or are
      nocturnally active have stronger negative population trends than species that are
      not attracted to light or are diurnal species. Our results indicate that
      artificial light at night is an important factor in explaining declines in moth
      populations in regions with high artificial night sky brightness. Our study
      supports efforts to reduce the impacts of artificial light at night by promoting
      lamps that do not attract insects and reduce overall levels of illumination in
      rural areas to reverse declines of moth populations.

PMID- 29215779
TI  - "Head-to-Middle" and "Head-to-Tail" cis-Prenyl Transferases: Structure of
      Isosesquilavandulyl Diphosphate Synthase.
AB  - We report the first X-ray crystallographic structure of the "head-to-middle"
      prenyltransferase, isosesquilavandulyl diphosphate synthase, involved in
      biosynthesis of the merochlorin class of antibiotics. The protein adopts the zeta
      or cis-prenyl transferase fold but remarkably, unlike tuberculosinol adenosine
      synthase and other cis-prenyl transferases (e.g. cis-farnesyl, decaprenyl,
      undecaprenyl diphosphate synthases), the large, hydrophobic side chain does not
      occupy a central hydrophobic tunnel. Instead, it occupies a surface pocket
      oriented at 90 degrees  to the hydrophobic tunnel. Product chain-length control
      is achieved by squeezing out the ligand from the conventional allylic S1 binding
      site, with proton abstraction being achieved using a diphosphate-Asn-Ser relay.
      The structures revise and unify our thinking as to the mechanism of action of
      many other prenyl transferases and may also be of use in engineering new
      merochlorin-class antibiotics.

PMID- 29215780
TI  - Triplet Tellurophene-Based Acceptors for Organic Solar Cells.
AB  - Triplet materials have been employed to achieve high-performing organic solar
      cells (OSCs) by extending the exciton lifetime and diffusion distances, while the
      triplet non-fullerene acceptor materials have never been reported for bulk
      heterojunction OSCs. Herein, for the first time, three triplet molecular
      acceptors based on tellurophene with different degrees of ring fusing were
      designed and synthesized for OSCs. Significantly, these molecules have long
      exciton lifetime and diffusion lengths, leading to efficient power conversion
      efficiency (7.52 %), which is the highest value for tellurophene-based OSCs. The
      influence of the extent of ring fusing on molecular geometry and OSCs performance
      was investigated to show the power conversion efficiencies (PCEs) continuously
      increased along with increasing the extent of ring fusing.

PMID- 29215781
TI  - Clinical prediction rules for mortality in patients with pulmonary embolism and
      cancer to guide outpatient management: a meta-analysis.
AB  - : Essentials Clinical prediction rules (CPRs) can stratify patients with
      pulmonary embolism (PE) and cancer. A meta-analysis was done to assess prognostic
      accuracy in CPRs for mortality in these patients. Eight studies evaluating ten
      CPRs were included in this study. CPRs should continue to be used with other
      patient factors for mortality risk stratification. SUMMARY: Background Cancer
      treatment is commonly complicated by pulmonary embolism (PE), which remains a
      leading cause of morbidity and mortality in these patients. Some guidelines
      recommend the use of clinical prediction rules (CPRs) to help clinicians identify
      patients at low risk of mortality and therefore guide care. Objective To
      determine and compare the accuracy of available CPRs for identifying cancer
      patients with PE at low risk of mortality. Methods A literature search of Medline
      and Scopus (January 2000 to August 2017) was performed. Studies
      deriving/validating >= 1 CPR for early post-PE all-cause mortality were included.
      A bivariate, random-effects model was used to pool sensitivity and specificity
      estimates for each CPR. Traditional random-effects meta-analysis was performed to
      estimate the weighted proportion of patients deemed at low risk of early
      mortality, mortality in low risk patients and odds ratios for death compared with
      higher-risk patients. Results Eight studies evaluating 10 CPRs were included. The
      highest sensitivities were observed with Hestia (98.1%, 95% confidence interval
      [CI] = 75.6-99.9%) and the EPIPHANY index (97.4%, 95% CI = 93.2-99.0%);
      sensitivities of remaining rules ranged from 59.9 to 96.6%. Of the six CPRs with
      sensitivities >= 95%, none had specificities > 33%. Random-effects meta-analysis
      suggested that 6.6-51.6% of cancer patients with PE were at low risk of
      mortality, 0-14.3% of low-risk patients died and low-risk patients had a 43-94%
      lower odds of death compared with those at higher risk. Conclusions Because of
      the limited total body of evidence regarding CPRs, their results, in conjunction
      with other pertinent patient-specific clinical factors, should continue to be
      used in identifying appropriate management for PE in patients with cancer.

PMID- 29215782
TI  - The effect of urinary Foley catheter substrate material on the antimicrobial
      potential of calixerene-based molecules.
AB  - AIMS: This study was to investigate the antimicrobial activity of a modified
      calixarene polymer bound to a silicone substrate in the presence of pathogens
      associated with catheter infections, Escherichia coli and Proteus mirabilis.
      METHODS AND RESULTS: The molecule and its constituent parts were studied bound
      and unbound to silicone substrates to ascertain growth effects. Minimum
      inhibitory and bactericidal concentrations were determined against E. coli and P.
      mirabilis. Biofilm growth was studied by immersing silicone discs seeded with
      either P. mirabilis or E. coli in artificial urine. Biofilms were assessed at 3,
      7 and 10 days. The coated material reduced bacterial cell density compared to the
      uncoated samples. Direct and indirect toxicity tests were conducted with a
      fibroblast cell line (3T3); coated and noncoated silicone samples were seeded
      with cells (1 * 104 /cm2 ) and incubated for 72 h. Hoechst propidium iodide
      staining identified delayed toxic effect from the coated and noncoated material
      leachate in all but the platinum-cured medical-grade silicone, which showed no
      evident toxicity. CONCLUSIONS: The calixerene polymer was determined to be the
      active part of the coating. Biofilm formation was dramatically reduced in the
      coated platinum-cured medical-grade silicone samples, but cell viability was
      reduced on the clinical-grade silicones regardless of coating in contrast to
      cells seeded on the platinum-cured medical-grade silicone. A delayed toxic
      response was evident to the extract of the coated and noncoated clinical-grade
      samples, indicating that the toxic effect is due to the underlying substrate.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study has established that the
      immobilized molecule enhances the antibacterial and antifouling properties of
      silicone, without toxicity. It also clearly demonstrates that regardless of
      coating efficacy, the substrate material has the capacity to disrupt its potency
      and change the nature of the material coating.

PMID- 29215783
TI  - Polymer Film Dewetting by Water/Surfactant/Good-Solvent Mixtures: A Mechanistic
      Insight and Its Implications for the Conservation of Cultural Heritage.
AB  - Aqueous nanostructured fluids (NSFs) have been proposed to remove polymer
      coatings from the surface of works of art; this process usually involves film
      dewetting. The NSF cleaning mechanism was studied using several techniques that
      were employed to obtain mechanistic insight on the interaction of a
      methacrylic/acrylic copolymer (Paraloid B72) film laid on glass surfaces and
      several NSFs, based on two solvents and two surfactants. The experimental results
      provide a detailed picture of the dewetting process. The gyration radius and the
      reduction of the Tg of Paraloid B72 fully swollen in the two solvents is larger
      for propylene carbonate than for methyl ethyl ketone, suggesting higher mobility
      of polymer chains for the former, while a nonionic alcohol ethoxylate surfactant
      was more effective than sodium dodecylsulfate in favoring the dewetting process.
      FTIR 2D imaging showed that the dewetting patterns observed on model samples are
      also present on polymer-coated mortar tiles when exposed to NSFs.

PMID- 29215784
TI  - Neither dark nor light but shades in-between: cocoa merits a finer sampling.

PMID- 29215785
TI  - Expression and functional characterization of two natural heparin-binding site
      variants of antithrombin.
AB  - : Essentials Heparin-binding site (HBS) variants of antithrombin (AT) are
      associated with thrombosis risk. HSB variants have, in general, normal
      progressive inhibitory activity but reduced heparin affinity. Thrombosis in HSB
      carriers has been primarily attributed to the loss of heparin cofactor activity.
      Results here demonstrate that HSB variants of AT also lack anti-inflammatory
      signaling functions. SUMMARY: Background Several heparin-binding site (HBS)
      variants of antithrombin (AT) have been identified that predispose carriers to a
      higher incidence of thrombosis. Thrombosis in carriers of HBS variants has been
      primarily attributed to a loss in their heparin-dependent anticoagulant function.
      Objective The objective of this study was to determine whether HSB mutations
      affect the anti-inflammatory functions of variants. Methods Two HBS variants of
      AT (AT-I7N and AT-L99F), which are known to be associated with a higher incidence
      of thrombosis, were expressed in mammalian cells and purified to homogeneity.
      These variants were characterized by kinetic assays followed by analysis of their
      activities in established cellular and/or in vivo inflammatory models. The
      possible effects of mutations on AT structure were also evaluated by molecular
      modeling. Results The results indicated that, whereas progressive inhibitory
      activities of variants were minimally affected, their heparin affinity and
      inhibitory activity in the presence of heparin were markedly decreased. Unlike
      wild-type AT, neither AT variant was capable of inhibiting activation of nuclear
      factor-kappaB or downregulation of expression of cell adhesion molecules in
      response to lipopolysaccharide (LPS). Similarly, neither variant elicited barrier
      protective activity in response to LPS. Structural analysis suggested that the
      L99F substitution locally destabilizes AT structure. Conclusions It is concluded
      that the L99F mutation of AT is associated with destabilization of the serpin
      structure, and that the loss of anti-inflammatory signaling function of the HBS
      variants may also contribute to enhanced thrombosis in carriers of HBS mutations.

PMID- 29215786
TI  - A Zero-Dimensional Organic Seesaw-Shaped Tin Bromide with Highly Efficient
      Strongly Stokes-Shifted Deep-Red Emission.
AB  - The synthesis and characterization is reported of (C9 NH20 )2 SnBr4 , a novel
      organic metal halide hybrid with a zero-dimensional (0D) structure, in which
      individual seesaw-shaped tin (II) bromide anions (SnBr42- ) are co-crystallized
      with 1-butyl-1-methylpyrrolidinium cations (C9 NH20+ ). Upon photoexcitation, the
      bulk crystals exhibit a highly efficient broadband deep-red emission peaked at
      695 nm, with a large Stokes shift of 332 nm and a high quantum efficiency of
      around 46 %. The unique photophysical properties of this hybrid material are
      attributed to two major factors: 1) the 0D structure allowing the bulk crystals
      to exhibit the intrinsic properties of individual SnBr42- species, and 2) the
      seesaw structure enabling a pronounced excited state structural deformation as
      confirmed by density functional theory (DFT) calculations.

PMID- 29215787
TI  - Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless
      Pharmacology and Optogenetics.
AB  - Combination of optogenetics and pharmacology represents a unique approach to
      dissect neural circuitry with high specificity and versatility. However,
      conventional tools available to perform these experiments, such as optical fibers
      and metal cannula, are limited due to their tethered operation and lack of
      biomechanical compatibility. To address these issues, a miniaturized, battery
      free, soft optofluidic system that can provide wireless drug delivery and optical
      stimulation for spatiotemporal control of the targeted neural circuit in freely
      behaving animals is reported. The device integrates microscale inorganic light
      emitting diodes and microfluidic drug delivery systems with a tiny stretchable
      multichannel radiofrequency antenna, which not only eliminates the need for bulky
      batteries but also offers fully wireless, independent control of light and fluid
      delivery. This design enables a miniature (125 mm3 ), lightweight (220 mg), soft,
      and flexible platform, thus facilitating seamless implantation and operation in
      the body without causing disturbance of naturalistic behavior. The proof-of
      principle experiments and analytical studies validate the feasibility and
      reliability of the fully implantable optofluidic systems for use in freely moving
      animals, demonstrating its potential for wireless in vivo pharmacology and
      optogenetics.

PMID- 29215788
TI  - Fingerprinting the Nature of Anions in Pyrylium Complexes: Dual Binding Mode for
      Anion-pi Interactions.
AB  - The interplay between noncovalent interactions that involve oxygenated
      heteroaromatic rings have been studied for the first time in this work. In
      particular, we report an advance in knowledge-based anion-pi interactions
      together with (C-H)+ ???anion contacts. To understand how the anion modulates
      these interactions, the synthesis of pyrylium salts with a variety of anions was
      performed by using an anionic metathesis methodology. The synthesized pyrylium
      complexes were classified in series, for example, anions derived from halogens,
      from oxoacids, from p-block elements, and from transition metals.
      Crystallographic data, DFT calculations, and NMR spectroscopy methods provided
      access to an overall insight into the noncovalent behavior of the anion in this
      kind of system. Based on the DFT calculations and 1 H NMR spectroscopy, pyrylium
      protons can be used as chemical tags to detect noncovalent interactions in this
      type of compound.

PMID- 29215789
TI  - Who owns the Brazilian carbon?
AB  - Brazil is one of the major contributors to land-use change emissions, mostly
      driven by agricultural expansion for food, feed, and bioenergy feedstock.
      Policies to avoid deforestation related to private commitments, economic
      incentives, and other support schemes are expected to improve the effectiveness
      of current command and control mechanisms increasingly. However, until recently,
      land tenure was unknown for much of the Brazilian territory, which has undermined
      the governance of native vegetation and challenged support and incentive
      mechanisms for avoiding deforestation. We assess the total extent of public
      governance mechanisms protecting aboveground carbon (AGC) stocks. We constructed
      a land tenure dataset for the entire nation and modeled the effects and
      uncertainties of major land-use acts on protecting AGC stocks. Roughly 70% of the
      AGC stock in Brazil is estimated to be under legal protection, and an additional
      20% is expected to be protected after areas in the Amazon with currently
      undesignated land undergo a tenure regularization. About 30% of the AGC stock is
      on private land, of which roughly two-thirds are protected. The Cerrado, Amazon,
      and Caatinga biomes hold about 40%, 30%, and 20% of the unprotected AGC,
      respectively. Effective conservation of protected and unprotected carbon will
      depend on successful implementation of the Forest Act, and regularization of land
      tenure in the Amazon. Policy development that prioritizes unprotected AGC stocks
      is warranted to promote conservation of native vegetation beyond the legal
      requirements. However, different biomes and land tenure structures may require
      different policy settings considering local and regional specifics. Finally, the
      fate of current AGC stocks relies upon effective implementation of command and
      control mechanisms, considering that unprotected AGC in native vegetation on
      private land only accounts for 6.5% of the total AGC stock.

PMID- 29215791
TI  - Protective effects of carbonyl iron against multiple low-dose streptozotocin
      induced diabetes in rodents.
AB  - Particulate adjuvants have shown increasing promise as effective, safe, and
      durable agents for the stimulation of immunity, or alternatively, the suppression
      of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron
      (CI) for the modulation of organ-specific autoimmune disease-type 1 diabetes
      (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that
      initiates beta cell death and triggers immune cell infiltration into the
      pancreatic islets. The results of this study indicate that the single in vivo
      application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice
      successfully counteracted the development of insulitis and hyperglycemia. The
      protective action was obtained either when CI was applied 7 days before,
      simultaneously with the first dose of streptozotocin, or 1 day after MLDS
      treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced
      the proportion of proinflammatory F4/80+ CD40+ M1 macrophages and activated T
      lymphocytes in the spleen. Moreover, the treatment down-regulated the number of
      inflammatory CD4+ IFN-gamma+ cells in pancreatic lymph nodes, Peyer's patches,
      and pancreas-infiltrating mononuclear cells, while simultaneously potentiating
      proportion of CD4+ IL17+ cells. The regulatory arm of the immune system
      represented by CD3+ NK1.1+ (NKT) and CD4+ CD25+ FoxP3+ regulatory T cells was
      potentiated after CI treatment. In vitro analysis showed that CI down-regulated
      CD40 and CD80 expression on dendritic cells thus probably interfering with their
      antigen-presenting ability. In conclusion, particulate adjuvant CI seems to
      suppress the activation of the innate immune response, which further affects the
      adaptive immune response directed toward pancreatic beta cells.

PMID- 29215790
TI  - Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin
      ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.
AB  - Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A
      (sLeX/A ), and alpha-1,3/4-fucosyltransferases (FUTs) in relation to increased
      disease progression and metastasis. These glycans in tumor circulating cells
      mediate binding to vascular E-selectin, initiating tumor extravasation. However,
      their role in breast carcinogenesis is still unknown. Here, we aimed to define
      the contribution of the fucosylated structures, including sLeX/A , to cell
      adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas
      (IDC), the most frequent type of breast cancer. We first analyzed expression of E
      selectin ligands in IDC tissue and established primary cell cultures from the
      tissue. We observed strong reactivity with E-selectin and anti-sLeX/A antibodies
      in both IDC tissue and cell lines, and expression of alpha-1,3/4 FUTs FUT4, FUT5,
      FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC
      biology, we immortalized a primary IDC cell line with human telomerase reverse
      transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2
      FF), a fucosylation inhibitor, completely abrogated its sLeX/A expression and
      dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic
      flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory
      ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment
      lowered the growth factor expression of CF1_T cells, prominently for FGF2,
      vascular endothelial growth factor, and transforming growth factor beta, and
      negatively affected activation of signal-regulating protein kinases 1 and 2 and
      p38 mitogen-activated protein kinase signaling pathways. These data indicate that
      fucosylation licenses several malignant features of IDC, such as cell adhesion,
      migration, proliferation, and growth factor expression, contributing to tumor
      progression.

PMID- 29215792
TI  - Deuterated Molecular Ruby with Record Luminescence Quantum Yield.
AB  - The recently reported luminescent chromium(III) complex 13+ ([Cr(ddpd)2 ]3+ ;
      ddpd=N,N'-dimethyl-N,N'-dipyridine-2-yl-pyridine-2,6-diamine) shows exceptionally
      strong near-IR emission at 775 nm in water under ambient conditions (Phi=11 %)
      with a microsecond lifetime as the ligand design in 13+ effectively eliminates
      non-radiative decay pathways, such as photosubstitution, back-intersystem
      crossing, and trigonal twists. In the absence of energy acceptors, such as
      dioxygen, the remaining decay pathways are energy transfer to high energy solvent
      and ligand oscillators, namely OH and CH stretching vibrations. Selective
      deuteration of the solvents and the ddpd ligands probes the efficiency of these
      oscillators in the excited state deactivation. Addressing these energy-transfer
      pathways in the first and second coordination sphere furnishes a record 30 %
      quantum yield and a 2.3 millisecond lifetime for a metal complex with an earth
      abundant metal ion in solution at room temperature.

PMID- 29215793
TI  - Genetic history of the African Sahelian populations.
AB  - From a biogeographic perspective, Africa is subdivided into distinct horizontal
      belts. Human populations living along the Sahel/Savannah belt south of the Sahara
      desert have often been overshadowed by extensive studies focusing on other
      African populations such as hunter-gatherers or Bantu in particular. However, the
      Sahel together with the Savannah bordering it in the south is a challenging
      region where people had and still have to cope with harsh climatic conditions and
      show resilient behaviours. Besides exponentially growing urban populations,
      several local groups leading various lifestyles and speaking languages belonging
      to three main linguistic families still live in rural localities across that
      region today. Thanks to several years of consistent population sampling
      throughout this area, the genetic history of the African Sahelian populations has
      been largely reconstructed and a deeper knowledge has been acquired regarding
      their adaptation to peculiar environments and/or subsistence modes. Distinct
      exposures to pathogens-in particular, malaria-likely contributed to their genetic
      differentiation for HLA genes. In addition, although food-producing strategies
      spread within the Sahel/Savannah belt relatively recently, during the last five
      millennia according to recent archaeological and archaeobotanical studies,
      remarkable amounts of genetic differences are also observed between sedentary
      farmers and more mobile pastoralists at multiple neutral and selected loci,
      reflecting both demographic effects and genetic adaptations to distinct cultural
      traits, such as dietary habits.

PMID- 29215794
TI  - Immigrant nurses' perceptions on cultural differences-based job concerns: A
      phenomenological study in Shanghai China.
AB  - AIMS AND OBJECTIVES: To explore the experiences of immigrant nurses working in
      Shanghai, China. BACKGROUND: With the development of China, population growth has
      been accelerating. Simultaneously, the number of immigrant nurses in Shanghai has
      been increasing dramatically. Meanwhile, their turnover rate is abnormally high,
      primarily because of job concerns stemming from cultural differences. An
      understanding of immigrant nurses' job concerns caused by cultural differences
      can be used to help them to work more efficiently and cohesively. We aimed to
      investigate immigrant nurses' lived experiences regarding job concerns caused by
      cultural differences in Shanghai, China. METHODS: This is a phenomenological
      study. In-depth semi-structured interviews were conducted with fifteen immigrant
      nurses from January-July 2016. Data were collected using audio-taped face-to-face
      interviews; the narratives were then transcribed verbatim and analysed
      thematically. RESULTS: The following three major themes emerged from the data:
      "communication difficulties," "work adjustment difficulties" and "life adjustment
      difficulties." The eight sub-themes within these were as follows: (i) language
      barrier, (ii) inability to integrate oneself with the local culture, (iii)
      feelings of unfairness, (iv) difficulty asking for leave, (v) feeling stressed,
      (vi) not being acclimatised, (vii) feeling helpless and (viii) feeling guilt at
      being unable to take care of their family. CONCLUSION: It is important to
      implement appropriate training programmes on language and cultural adaptation for
      immigrant nurses. To enhance integrate immigrant nurses into Shanghai's society,
      more support needs to be provided. RELEVANCE TO CLINICAL PRACTICE: Administrators
      in hospitals should pay attention to immigrant nurses' job concerns that are
      caused by cultural differences and provide timely and effective assistance.

PMID- 29215795
TI  - Uterine caesarean closure techniques affect ultrasound findings and maternal
      outcomes: a systematic review and meta-analysis.
AB  - BACKGROUND: Caesarean section (CS) rates are rising globally. Long-term adverse
      outcomes after CS might be reduced when the optimal uterine closure technique
      becomes evident. OBJECTIVE: To determine the effect of uterine closure techniques
      after CS on maternal and ultrasound outcomes. SEARCH STRATEGY: Literature search
      in electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      or prospective cohort studies that evaluated uterine closure techniques and
      reported on ultrasound findings, perioperative or long-term outcomes. DATA
      COLLECTION AND ANALYSIS: Twenty studies (15 053 women) were included in our meta
      analyses for various outcomes. We calculated pooled risk ratios (RR) and weighted
      mean differences (WMD) with 95% CI through random-effect analysis. MAIN RESULTS:
      Residual myometrium thickness (RMT), reported in eight studies (508 women),
      decreased by 1.26 mm after single- compared with double-layer closure (95% CI 
      1.93 to -0.58), particularly when locked sutures were used. Healing ratio
      [RMT/adjacent myometrium thickness (AMT)] decreased after single-layer closure
      (WMD -7.74%, 95% CI -13.31 to -2.17), particularly in the case of locked sutures.
      Niche prevalence increased (RR 1.71, 95% CI 1.11-2.62) when the decidua was
      excluded. Dysmenorrhea occurred more often in the single-layer group (RR 1.23,
      95% CI 1.01-1.48), whereas incidence of uterine rupture was similar (RR 1.91, 95%
      CI 0.63-5.74). CONCLUSION: Double-layer unlocked sutures are preferable to single
      layer locked sutures regarding RMT, healing ratio and dysmenorrhoea. Excluding
      the decidua seems to result in higher niche prevalence. As thin residual
      myometrium or niches may serve as intermediates for gynaecological and
      reproductive outcomes, future studies should focus on these outcomes. TWEETABLE
      ABSTRACT: #Uterineclosuretechniques after #caesarean affect #longtermoutcomes.

PMID- 29215796
TI  - Polarization-multiplexed, dual-beam swept source optical coherence tomography
      angiography.
AB  - A polarization-multiplexed, dual-beam setup is proposed to expand the field of
      view (FOV) for a swept source optical coherence tomography angiography (OCTA)
      system. This method used a Wollaston prism to split sample path light into 2
      orthogonal-polarized beams. This allowed 2 beams to shine on the cornea at an
      angle separation of ~14 degrees , which led to a separation of ~4.2 mm on the
      retina. A 3-mm glass plate was inserted into one of the beam paths to set a
      constant path length difference between the 2 polarized beams so the
      interferogram from the 2 beams are coded at different frequency bands. The
      resulting OCTA images from the 2 beams were coded with a depth separation of ~2
      mm. A total of 5 * 5 mm2 angiograms from the 2 beams were obtained simultaneously
      in 4 seconds. The 2 angiograms then were montaged to get a wider FOV of ~5 * 9.2
      mm2 .

PMID- 29215797
TI  - Rubicon: LC3-associated phagocytosis and beyond.
AB  - Rubicon (Rubcn) was initially identified as a component of the Class III PI3K
      complex and a negative regulator of canonical autophagy and endosomal
      trafficking. However, Rubicon has attracted the most notoriety because of its
      critical role in LC3-associated phagocytosis (LAP), a form of noncanonical
      autophagy that utilizes some components of the autophagy machinery to process
      extracellular cargo. Additionally, Rubicon has been identified as a key modulator
      of the inflammatory response and viral replication. In this review, we discuss
      the known functions of Rubicon in LAP and other signaling pathways and examine
      the disease pathologies associated with Rubicon dysfunction in animal models and
      humans.

PMID- 29215798
TI  - Electrochemical Synthesis of Aryl Iodides by Anodic Iododesilylation.
AB  - An electrochemical access to iodinated aromatic compounds starting from
      trimethylsilyl-substituted arenes is presented. By design of experiments, highly
      efficient and mild conditions were identified for a wide range of substrates. A
      functional group stability test and the synthesis of an important 3
      iodobenzylguanidine radiotracer illustrate the scope of this process.

PMID- 29215799
TI  - Comparison of PrestoBlue(r) and plating method to evaluate antimicrobial activity
      of ascorbic acid, boric acid and curcumin in an in vitro gastrointestinal model.
AB  - AIMS: To compare the conventional plating method vs a fluorometric method using
      PrestoBlue(r) as a dye by determining the antimicrobial activity of two organic
      acids and curcumin (CUR) against Salmonella Enteritidis in an avian in vitro
      digestion model that simulates the crop, proventriculus and intestine. METHODS
      AND RESULTS: A concentration of 108  CFU per ml of S. Enteritidis was exposed to
      groups with different rates of ascorbic acid (AA), boric acid (BA) and CUR.
      Significant differences were observed when the means of the treatments were
      compared with the controls in the compartments that simulate the crop and
      intestine (P < 0.05). Ascorbic acid alone and high rates of AA in the mixtures
      were the most efficient treatments in the crop compartment. However, in the
      intestinal compartment BA alone and at different rates in the mixture BA-CUR (1 :
      1) were the best treatments to decrease the concentration of S. Enteritidis.
      CONCLUSIONS: The results of this study suggest that there could be an
      antagonistic bactericidal effect between AA and CUR and AA and BA as well as a
      synergistic bactericidal effect between BA and CUR. SIGNIFICANCE AND IMPACT OF
      THE STUDY: These findings may contribute to the development of a formulation with
      microencapsulated compounds to liberate them in different compartments to combat
      S. Enteritidis infections in broiler chickens.

PMID- 29215800
TI  - Microencapsulation for cell therapy of type 1 diabetes mellitus: The interplay
      between common beliefs, prejudices and real progress.
AB  - Critical discussion on pancreatic islets/insulin producing cells
      microencapsulation within highly purified alginic acid-derived bioplymers: past,
      present and future.

PMID- 29215801
TI  - The barriers to the prevention of ventilator-associated pneumonia from the
      perspective of critical care nurses: A qualitative descriptive study.
AB  - AIMS AND OBJECTIVES: The aim of this study was to explore the perspectives of
      Iranian critical care nurses on the barriers to ventilator-associated pneumonia
      prevention in intensive care units. BACKGROUND: Most patients hospitalized in
      intensive care units need mechanical ventilation. One of the most prevalent and
      serious complications of mechanical ventilation is ventilator-associated
      pneumonia. There are different barriers to the prevention of this kind of
      pneumonia. DESIGN: Qualitative descriptive design was used. METHODS: In this
      qualitative study, 23 critical care nurses were recruited via purposive sampling.
      Semi-structured interviews were done for data collection. The interviews were
      recorded digitally, transcribed word by word, and analyzed using the inductive
      content analysis approach. RESULTS: The barriers to the prevention of ventilator
      associated pneumonia fell into three main categories, namely nurses' limited
      professional competence, unfavorable environmental conditions, and passive human
      resource management. The 10 subcategories of these main categories were
      unfavorable professional attitude, limited professional knowledge, low job
      motivation, limited professional accountability, non-standard physical structure,
      inadequate or inappropriate equipment, heavy workload, staff shortage, inadequate
      staff training, and ineffective supervision. CONCLUSION: The barriers to the
      prevention of ventilator-associated pneumonia in intensive care units are very
      diverse and complex and include a wide range of interrelated personal,
      environmental, and organizational barriers. RELEVANCE TO CLINICAL PRACTICE: This
      study created a better understanding of the barriers to ventilator-associated
      pneumonia prevention. Moreover, highlighted the importance of sufficient
      resources, adequate staffing level, and contextually-appropriate evidence-based
      guidelines for effective ventilator-associated pneumonia prevention.

PMID- 29215802
TI  - Does stigma curvature promote delayed selfing? An experimental investigation in
      Triodanis perfoliata (Campanulaceae).
AB  - Self-fertilisation that is delayed until after opportunities for outcrossing have
      ceased has been argued to provide both the reproductive assurance benefits of
      selfing and the genetic advantages of outcrossing. In the Campanulaceae,
      presentation of pollen on stylar hairs and progressive stigma curvature have been
      hypothesised to facilitate delayed selfing, but experimental tests are lacking.
      Stigma curvature is common in Campanula, a genus largely characterised by self
      incompatibility, and therefore is unlikely to have initially evolved to promote
      self-fertilisation. In derived self-compatible species, however, stigma curvature
      might serve the secondary function of delayed selfing. We investigated delayed
      selfing in Triodanis perfoliata, a self-compatible relative of Campanula. Using
      floral manipulation experiments and pollen tube observations, we quantified the
      extent and timing of self-pollination. Further, we hypothesised that, if stigma
      curvature provides the benefit of delayed selfing in Triodanis, selection should
      have favoured retention of self-pollen through the loss of a stylar hair
      retraction mechanism. Results of a stigma removal experiment indicated that
      autonomous selfing produces partial seed set, but only some selfing was delayed.
      Pollen tube observations and a flower senescence assay also supported the finding
      of partial delayed selfing. Scanning electron microscopy revealed that pollen
      collecting hairs retract during anthesis, which may limit the extent of delayed
      selfing. Delayed selfing appeared to be only partially effective in T.
      perfoliata. The stylar hair retraction in this species would seem to contradict
      selection for selfing. We suggest that caution and rigour are needed in
      interpreting floral traits as adaptive mechanisms for delayed selfing.

PMID- 29215803
TI  - Reference Values for Spirometry Derived Using Lambda, Mu, Sigma (LMS) Method in
      Korean Adults: in Comparison with Previous References.
AB  - BACKGROUND: The present study aimed to update the prediction equations for
      spirometry and their lower limits of normal (LLN) by using the lambda, mu, sigma
      (LMS) method and to compare the outcomes with the values of previous spirometric
      reference equations. METHODS: Spirometric data of 10,249 healthy non-smokers
      (8,776 females) were extracted from the fourth and fifth versions of the Korea
      National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009; V, 2010
      2012). Reference equations were derived using the LMS method which allows
      modeling skewness (lambda [L]), mean (mu [M]), and coefficient of variation
      (sigma [S]). The outcome equations were compared with previous reference values.
      RESULTS: Prediction equations were presented in the following form: predicted
      value = e{a + b * ln(height) + c * ln(age) + M - spline}. The new predicted
      values for spirometry and their LLN derived using the LMS method were shown to
      more accurately reflect transitions in pulmonary function in young adults than
      previous prediction equations derived using conventional regression analysis in
      2013. There were partial discrepancies between the new reference values and the
      reference values from the Global Lung Function Initiative in 2012. CONCLUSION:
      The results should be interpreted with caution for young adults and elderly
      males, particularly in terms of the LLN for forced expiratory volume in one
      second/forced vital capacity in elderly males. Serial spirometry follow-up,
      together with correlations with other clinical findings, should be emphasized in
      evaluating the pulmonary function of individuals. Future studies are needed to
      improve the accuracy of reference data and to develop continuous reference values
      for spirometry across all ages.

PMID- 29215805
TI  - Development of the Suicide Risk Scale for Medical Inpatients.
AB  - BACKGROUND: Inpatient suicide is one of the major issues related with hospital
      patient safety. Although there are many studies addressing suicide in the
      psychiatric unit, little is known about suicide in a medical setting. This study
      included the development and validation of a screening tool for the assessment of
      suicide risk, specialized for medical inpatients. METHODS: The preliminary
      questionnaire was based on review of previous suicide ideation scales, mood
      scales, and clinical experiences of psychiatrists and clinical psychologists in
      Korea. Initially, the questionnaire consisted of 12 questions. One hundred adult
      medical inpatients were asked to perform the questionnaire. Explorative factor
      analysis was used to examine construct validity. Concurrent validity was
      evaluated by comparison with the Korean versions of the Beck Scale for Suicide
      Ideation (BSI), the Beck Hopelessness Scale (BHS), and the Hospital Anxiety and
      Depression Scale (HADS). RESULTS: Five questions were removed from the
      preliminary questionnaire by explorative factor analysis and seven questions
      remained to comprise the Suicide Risk Scale for Medical inpatients (SRSM).
      Explorative factor analysis showed that the SRSM is composed of a single factor.
      SRSM was highly reliable in terms of internal consistency (Cronbach's alpha
      0.91). Concurrent validity with the BSI, BHS, and HADS was statistically
      significant. The proposed cut-off score of the SRSM was five. CONCLUSION: In
      conclusion, the SRSM is a valid and reliable measure for screening suicide risks
      in medical inpatients.

PMID- 29215804
TI  - Cognitive Function and Neuropsychological Comorbidities in Children with Newly
      Diagnosed Idiopathic Epilepsy.
AB  - BACKGROUND: In this study, we aimed to identify cognitive function and
      neuropsychological comorbidities in children with newly diagnosed idiopathic
      epilepsy. METHODS: We retrospectively reviewed the records of 97 antiepileptic
      drug-naive children (9.7 +/- 2.9 years; 54 males and 43 females) with newly
      diagnosed idiopathic epilepsy, all of whom underwent a neuropsychological
      battery. The battery consisted of the Korean Wechsler Intelligence Scale,
      Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, ADHD Diagnostic
      System, Children's Depression Inventory, and State-Trait Anxiety Inventory for
      Children. We investigated association between scores of the neuropsychological
      battery and epilepsy classification, lateralization of interictal epileptiform
      discharges (IEDs) on electroencephalography (EEG), and variables related to
      seizures. RESULTS: Thirteen patients (14.3%) had ADHD symptoms. Three patients
      (4.1%) had depressive symptoms, and 9 (12.3%) had anxiety symptoms. Patients with
      idiopathic generalized epilepsy (IGE) had significantly lower full-scale
      intelligence and performance intelligence quotient scores than patients with
      idiopathic localization-related epilepsy (ILRE) (89.0 +/- 17.6 vs. 96.3 +/- 14.8;
      P = 0.030 and 88.9 +/- 16.3 vs. 97.0 +/- 16.4; P = 0.016, respectively). Patients
      with ILRE having unilateral IEDs had significantly higher full-scale intelligence
      quotient scores than patients with ILRE having bilateral IEDs and patients with
      IGE (99.9 +/- 12.2 vs. 93.7 +/- 16.1 vs. 89.0 +/- 17.6; P = 0.039, respectively).
      CONCLUSION: Our results suggest that idiopathic epilepsy may be accompanied by
      various neuropsychological comorbidities even at initial diagnosis. Patients with
      IGE and ILRE having bilateral IEDs on EEG appear more likely to be at high risk
      of decreased cognitive function.

PMID- 29215806
TI  - Development of an LCD-Based Visual Field System.
AB  - BACKGROUND: The present study investigated the diagnostic effectiveness of an LCD
      based visual field testing system (LVF) in comparison with the standard automated
      perimetry Humphrey Field Analyzer II-750i (HFA). METHODS: A randomized controlled
      crossover study was conducted with 202 normal and 128 glaucomatous eyes using
      both LVF and HFA. The visual field testing systems were compared in terms of mean
      deviation (MD), pattern standard deviation (PSD), and area under the receiver
      operating characteristics curve (AUC) of MD and PSD differentiating the normal
      and glaucomatous eyes. RESULTS: Significant correlations were found between MD
      measurements from LVF and those from HFA for normal eyes (r = 0.342) and
      glaucomatous eyes (r = 0.796); slightly higher significant correlations were
      identified between PSD measurements from LVF and those from HFA for normal eyes
      (r = 0.363) and glaucomatous eyes (r = 0.828). Furthermore, high AUCs of MD were
      found as 0.786 for LVF and 0.868 for HFA and AUCs of PSD as 0.913 for LVF and
      0.932 for HFA. CONCLUSION: The comparison results of the present study support
      the competence of LVF compared with HFA in visual field testing for early
      detection of glaucoma.

PMID- 29215807
TI  - Utilization of Osteoporosis-Related Health Services: Use of Data from the Korean
      National Health Insurance Database 2008-2012.
AB  - BACKGROUND: Osteoporosis and its related fractures are increasingly being
      recognized as major health problems because of the rapidly increasing elderly
      population. In this study, we investigated the annual trend of osteoporosis
      related health services utilization. METHODS: Participants aged over 50 years
      were identified from the Korean National Health Insurance Service database
      between 2008 and 2012. Health service utilization rate and treatment rate were
      calculated through the operational definition. RESULTS: In this period, the
      number of osteoporosis patients, aged over 50 years, using the medical service,
      increased by 33.2%. This increase was higher in males than in females. Moreover,
      the number of newly diagnosed osteoporosis patients increased by 4.3% in women
      and 20.4% in men. To estimate the proportion of osteoporosis patients who utilize
      medical services, we analyzed prevalence data from the Korea National Health and
      Nutrition Examination Survey from 2008 to 2010. Less than 60% of patients with
      osteoporosis were estimated to have utilized medical services because of
      osteoporosis. Drug treatment rates were 34.1%, 31.1%, and 33.5% in 2008, 2009,
      and 2010, respectively. CONCLUSION: This study demonstrated an increasing trend
      in the utilization of the osteoporosis-related health services from 2008 to 2012
      in Korea. The proportion of newly diagnosed osteoporosis patients and the
      prevalence of access to medical services increased more in men than in women.
      Therefore, an increasing need for prevention and treatment of male osteoporosis
      was observed. The osteoporosis treatment rate was lower than that for other
      chronic diseases; more efforts are needed to improve awareness regarding
      osteoporosis treatment.

PMID- 29215808
TI  - Prognostic Performance Evaluation of the International Society on Thrombosis and
      Hemostasis and the Korean Society on Thrombosis and Hemostasis Scores in the
      Early Phase of Trauma.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) contributes to poor
      outcome in the early phase of trauma. We aimed to analyze and compare the
      prognostic performances of the International Society on Thrombosis and Hemostasis
      (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH) scores in the
      early phase of trauma. METHODS: Receiver operating characteristics analysis was
      used to examine the prognostic performance of both scores, and multivariate
      analysis was used to estimate the prognostic impact of the ISTH and KSTH scores
      in the early phase of trauma. The primary outcome was 24-hour mortality and the
      secondary outcome was massive transfusion. RESULTS: Of 1,229 patients included in
      the study, the 24-hour mortality rate was 7.6% (n = 93), and 8.1% (n = 99) of
      patients who received massive transfusions. The area under the curves (AUCs) of
      the KSTH and ISTH scores for 24-hour mortality were 0.784 (95% confidence
      interval [CI], 0.760-0.807) and 0.744 (95% CI, 0.718-0.768), respectively. The
      AUC of KSTH and ISTH scores for massive transfusion were 0.758 (95% CI, 0.734
      0.782) and 0.646 (95% CI, 0.619-0.673), respectively. The AUCs of the KSTH score
      was significantly different from those of the ISTH score. Overt DIC according to
      KSTH criteria only, was independently associated with 24-hour mortality (odds
      ratio [OR], 2.630; 95% CI, 1.456-4.752). Only the KSTH score was independently
      associated with massive transfusion (OR, 1.563; 95% CI, 1.182-2.068). CONCLUSION:
      The KSTH score demonstrates a better prognostic performance for outcomes than the
      ISTH score in the early phase of trauma.

PMID- 29215809
TI  - The Youngest Survivor with Gestational Age of 215/7 Weeks.
AB  - The decision whether or not to resuscitate extremely low gestational age (GA)
      infants is recommended to be individualized according to antenatal counseling
      with parents, neonatologists, and obstetricians. A GA of 220/7-236/7 weeks is
      generally considered as the lower end of the range where infants can be
      candidates for selective resuscitation. Below this lower end of periviable
      gestation, resuscitation is usually not considered and survivors are rarely
      reported. To date, the youngest survivor is an infant with a GA of 216/7 weeks
      reported in the English medical literature. Here, we report the case of a female
      infant, the first twin conceived through in vitro fertilization, with a GA of
      215/7 weeks, who was resuscitated initially according to strong parental wishes
      after antenatal counseling and is still surviving at 43 months of age with fairly
      good neurodevelopmental outcome.

PMID- 29215810
TI  - Pediatric Deaths Attributed to Complex Chronic Conditions over 10 Years in Korea:
      Evidence for the Need to Provide Pediatric Palliative Care.
AB  - BACKGROUND: Pediatric palliative care (PPC) is the active total care of children
      suffering from life-threatening illnesses. Palliative care includes symptom
      management, psychosocial support, and end-of-life care. Despite significant
      advances in disease diagnosis and treatment, resources for PPC of children with
      serious illnesses are limited in Korea. This study aimed to investigate the
      scale, time trends, disease composition, regional distribution, and unmet needs
      of children dying from complex chronic conditions (CCCs). METHODS: We examined
      available information on children who died of CCCs from 2005 to 2014 using the
      cause of death statistics in Korea. RESULTS: There were 36,808 cases of pediatric
      deaths in Korea during that 10-year period, one-third (12,515 cases, 34.0%) of
      which were due to CCCs. In 2014, there were 1,044 cases of pediatric deaths due
      to CCCs (9.8 deaths per 100,000 children) in Korea. The rate of pediatric deaths
      due to CCCs has declined over this 10-year period. Among CCCs, malignancy was the
      most common cause of death overall, as well as in children and adolescents,
      whereas neonatal disorders were the most common cause of death in infants.
      Although over 1,000 children die from chronic illnesses each year, there are no
      hospitals or institutes in Korea that meet the minimum standards for specialized
      PPC. CONCLUSION: To improve the quality of life of children suffering from CCCs
      and to support their families who face enormous distress, children with CCCs
      should be able to access adequate palliative care services. Health authorities
      should consider supporting the establishment of PPC centers and increasing PPC
      accessibility in Korea.

PMID- 29215811
TI  - Impacts of Return-to-Work Type and Period on Job Retention in Workers with
      Occupational Injuries and Diseases.
AB  - BACKGROUND: Despite the necessity of job retention in achieving return-to-work
      (RTW) goals, many workers leave their jobs after returning to work. The objective
      of this study was to examine the impacts of RTW type and period on job retention
      in Korean workers with occupational injuries and diseases. METHODS: Data were
      derived from the Panel Study of Worker's Compensation Insurance, including data
      from 2,000 systemically sampled workers who had finished recuperation in 2012;
      three waves of survey data were included in the analyses. Workers who returned to
      work (n = 1,610) were included in the analysis of the relationship between RTW
      type and job retention, and 664 workers who returned to their original workplaces
      were included in the analysis of the relationship between RTW period and job
      retention. The participants completed a questionnaire, and administrative data
      were provided by workers' compensation insurance. RESULTS: A Cox proportional
      hazards regression analysis showed an increased hazard ratio (HR) for non
      retention of 2.66 (95% confidence interval, 2.11-3.35) in reemployed workers
      compared to that in workers returning to their original workplaces. Among workers
      returning to their original workplaces, HRs for non-retention were increased in
      workers with a RTW period of 13-24 months (3.03 [1.52-6.04]) and > 24 months
      (5.33 [2.14-13.25]) compared to workers with a RTW period of <= 3 months.
      CONCLUSION: RTW type and period were significantly related to job retention,
      suggesting that policies for promoting job retention rate should be implemented.

PMID- 29215812
TI  - Prevalence of Overweight and Income Gaps in 245 Districts of Korea: Comparison
      Using the National Health Screening Database and the Community Health Survey,
      2009-2014.
AB  - BACKGROUND: We compared age-standardized overweight prevalence and their income
      gaps at the level of district in Korea using the National Health Screening
      Database (NHSD) and the Community Health Survey (CHS). METHODS: We analyzed
      39,093,653 subjects in the NHSD and 926,580 individuals in the CHS between 2009
      and 2014. For the comparison of body mass index (BMI) distributions, data from
      26,100 subjects in the Korea National Health and Nutrition Examination Survey
      (KNHANES) were also analyzed. We calculated the age-standardized overweight
      prevalence and its interquintile income gap at the district level. We examined
      the magnitudes of the between-period correlation for age-standardized overweight
      prevalence. The differences in overweight prevalence and its income gap between
      the NHSD and the CHS were also investigated. RESULTS: The age-adjusted mean BMI
      from the CHS was lower than those from the NHSD and the KNHANES. The magnitudes
      of the between-period correlation for overweight prevalence were greater in the
      NHSD compared to the CHS. We found that the district-level overweight prevalence
      in the NHSD were higher in all districts of Korea than in the CHS. The
      correlation coefficients for income gaps in overweight prevalence between the two
      databases were relatively low. In addition, when using the NHSD, the district
      level income inequalities in overweight were clearer especially among women than
      the inequalities using the CHS. CONCLUSION: The relatively large sample size for
      each district and measured anthropometric data in the NHSD are more likely to
      contribute to valid and reliable measurement of overweight inequality at the
      district level in Korea.

PMID- 29215813
TI  - Kidney Transplantation in Patients with Atypical Hemolytic Uremic Syndrome due to
      Complement Factor H Deficiency: Impact of Liver Transplantation.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that is
      often associated with genetic defects. Mutations of complement factor H (CFH) are
      the most common genetic defects that cause aHUS and often result in end-stage
      renal disease. Since CFH is mainly produced in the liver, liver transplantation
      (LT) has been performed in patients with defective CFH. METHODS: The clinical
      courses of four kidney allograft recipients who lost their native kidney
      functions due to aHUS associated with a CFH mutation were reviewed. RESULTS:
      Subject A underwent kidney transplantation (KT) twice, aHUS recurred and the
      allograft kidney failed within a few years. Subject B received a KT and soon
      experienced a recurrence of aHUS coinciding with infection. Her allograft kidney
      function has worsened, and she remains on plasma infusion therapy. Subject C
      underwent LT followed by KT. She is doing well without plasma infusion therapy
      after combined LT-KT for 3 years. Subject D received KT following LT and is now
      recurrence-free from aHUS. CONCLUSION: In patients with aHUS associated with a
      CFH mutation, KT without LT was complicated with a recurrence of aHUS, which
      might lead to allograft loss. Conversely, LT was successful in preventing the
      recurrence of aHUS and thus might be another option for a recurrence-free life
      for aHUS patients associated with CFH mutation.

PMID- 29215814
TI  - Safety and Efficacy of B-domain Deleted Third Generation Recombinant Factor VIII
      (GreenGene FTM) in Korean Patients with Hemophilia A: Data from a Post-marketing
      Surveillance Study.
AB  - BACKGROUND: New B-domain deleted third generation recombinant factor VIII (FVIII;
      GreenGene FTM, beroctocog alfa) was launched in 2010. We determined safety and
      efficacy of GreenGene FTM during routine clinical practice in patients with
      hemophilia A over a period of 12 months. METHODS: From July 2010 to July 2014, a
      total of 136 hemophilia A patients were enrolled in a post-marketing surveillance
      (PMS) study. Among them, 134 patients were assessed for drug safety and 114
      patients were analyzed for drug efficacy. Patients with differing hemophilia A
      severities and medical histories were monitored during 12 months of prophylactic
      and/or on-demand therapy. RESULTS: Among 134 patients evaluated, 85 (63.4%) had
      severe hemophilia. Ninety-two received a total of 1,266,077 units for
      prophylaxis, and 42 received 516,491 units for bleeding episodes. Three patients
      developed inhibitors. In 112 previously treated patients, one patient (0.9%)
      developed inhibitor after intensive FVIII treatment for surgery. Among 22
      previously untreated patients, inhibitors were observed in 2 infants (9.1%).
      Overall, there were a total of 47 adverse events (other than inhibitors) of all
      types in 30 patients (22.4%), 11 in 10 patients (7.5%) of which were considered
      showing serious adverse events (SAEs); most of which were hemorrhages at
      different sites. None of the SAEs were judged as product related. An
      excellent/good efficacy rate of 91.3% for hemostasis and 89.4% for hemorrhage
      prevention was recorded. CONCLUSION: The results of this PMS study support the
      use of GreenGene FTM as safe and efficacious in hemorrhage prevention and
      treatment of hemophilia A. These results are consistent with the findings from
      previously published GreenGene FTM studies.

PMID- 29215815
TI  - Plasma MicroRNA-21, 26a, and 29a-3p as Predictive Markers for Treatment Response
      Following Transarterial Chemoembolization in Patients with Hepatocellular
      Carcinoma.
AB  - BACKGROUND: We investigated an association between the levels of plasma microRNA
      (miRNA)-21, -26a, and -29a-3p and treatment outcomes following transarterial
      chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).
      METHODS: A total of 198 patients with TACE-treated HCC were followed up for TACE
      refractoriness and liver transplantation (LT)-free survival. Pretreatment plasma
      miRNA-21, -26a, and -29a-3p levels were measured using quantitative real-time
      polymerase chain reaction. RESULTS: During the mean follow-up of 22.3 (range, 0.7
      79) months, 118 (59.6%) patients exhibited TACE refractoriness. Multivariate
      analyses showed that expression of a specific combination of miRNAs (miRNA-21 >=
      2.5, miRNA-26a >= 1.5, and miRNA-29a-3p < 0.4) was associated with early TACE
      refractoriness (within 1 year; hazard ratio [HR], 2.32; 95% confidence interval
      [CI], 1.08-4.99; P = 0.031) together with tumor size (HR, 4.62; 95% CI, 1.50
      14.21; P = 0.008), and macrovascular invasion (HR, 3.80; 95% CI, 1.19-12.20; P =
      0.025). However, miRNA-21, -26a, and -29a-3p levels were not significantly
      associated with overall TACE refractoriness or LT-free survival. Additionally,
      large tumor size and macrovascular invasion were common predictive factor of
      overall TACE refractoriness and survival. CONCLUSION: Combination of plasma miRNA
      21, -26a, and -29a-3p expression could predict early TACE refractoriness in
      patients with TACE-treated HCC.

PMID- 29215817
TI  - Fostering Strategic Changes in Publishing: Journal of Korean Medical Science in
      2018.

PMID- 29215816
TI  - Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung
      Cancer Harboring HER2 Mutation: Case Report.
AB  - Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung
      cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to
      HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined
      especially in eastern populations. We provide evidence of clinical benefit of
      afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously
      failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing
      of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A>G), which has never
      been reported. The patient was treated with afatinib for more than four months.
      She showed rapid radiologic response within a month, and maintained stable state
      until the last dose of afatinib.

PMID- 29215818
TI  - Lead, Mercury, and Cadmium Exposure in the Korean General Population.
AB  - BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known
      environmental pollutants. They are unnecessary in the biological processes of
      humans. This study was performed to estimate the representative background
      exposure levels to the metals by measuring concentrations in whole blood of the
      Korean general population. METHODS: This population-based cross-sectional study
      included 4,000 subjects (1,886 males and 2,114 females) 0-83 years of age in 2010
      and 2011. Adult subjects (>= 19 years of age) were collected by sex- and age
      stratified probability method, and preschool- and school-aged subjects were
      recruited by a cluster sampling method. Written consent was provided prior to
      blood sampling. Pb and Cd blood concentrations were determined by a flameless
      atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg
      analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was
      1.82 MUg/dL, 1.83 MUg/dL, and 3.78 MUg/dL, respectively. The respective values
      were 2.92 MUg/L, 2.87 MUg/L, 9.12 MUg/L for Hg, and 0.56 MUg/L, 0.59 MUg/L, 2.20
      MUg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex
      difference was observed, respectively, in subjects 0-4 years of age for Pb and in
      subjects less than 20 years for Hg. However, blood Cd was higher in females than
      in males and no sex difference was observed in subjects < 30 years of age.
      CONCLUSION: This study provides representative data of human exposure to Pb, Hg,
      and Cd covering whole age groups of the general population in Korea.

PMID- 29215819
TI  - Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross
      sectional Study.
AB  - BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The
      present study aimed to identify the prevalence of malnutrition in hospitalized
      patients in Korea, evaluate the association between malnutrition and clinical
      outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter
      cross-sectional study was performed with 300 patients recruited from among the
      patients admitted in 25 hospitals on January 6, 2014. Nutritional status was
      assessed by using the Subjective Global Assessment (SGA). Demographic
      characteristics and underlying diseases were compared according to nutritional
      status. Logistic regression analysis was performed to identify the risk factors
      of malnutrition. Clinical outcomes such as rate of admission in intensive care
      units, length of hospital stay, and survival rate were evaluated. RESULTS: The
      prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (>= 70
      years), admission for medical treatment or diagnostic work-up, and underlying
      pulmonary or oncological disease were associated with malnutrition. Old age and
      admission for medical treatment or diagnostic work-up were identified to be risk
      factors of malnutrition in the multivariate analysis. Patients with malnutrition
      had longer hospital stay (SGA A = 7.63 +/- 6.03 days, B = 9.02 +/- 9.96 days, and
      C = 12.18 +/- 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A =
      97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common
      in hospitalized patients, and resulted in longer hospitalization and associated
      lower survival rate. The rate of malnutrition tended to be higher when the
      patient was older than 70 years old or hospitalized for medical treatment or
      diagnostic work-up compared to elective surgery.

PMID- 29215820
TI  - Antiviral Efficacy of Tenofovir Monotherapy in Children with Nucleos(t)ide-naive
      Chronic Hepatitis B.
AB  - BACKGROUND: The purpose was to compare the efficacy between tenofovir disoproxil
      fumarate (TDF) and lamivudine (LMV) in children with nucleos(t)ide-naive chronic
      hepatitis B (CHB) infection. Patients with CHB were treated with TDF in the
      immune-reactive phase and compared with a historical control group of patients
      treated with LMV before the TDF era. METHODS: Hepatitis B virus (HBV) DNA titer
      decrements (> 3 log10 IU/mL) were monitored after treatment initiation. The
      treatment duration for HBV DNA clearance (< 357 IU/mL) and complete response
      (HBeAg loss and HBV DNA clearance) were analyzed. The follow-up period was 96
      weeks. RESULTS: Sixteen patients were treated with TDF and compared with a
      historical control group of 24 patients treated with LMV. HBV DNA decrement (> 3
      log10 IU/mL) was achieved in 100% (16/16) of the TDF group but in only 62.5%
      (15/24) of the LMV group (P = 0.005) at 48 weeks. The HBV DNA clearance (< 357
      IU/mL) in the TDF and LMV groups was, respectively, as follows: 62.5% (10/16) and
      25.0% (6/24) at 12 weeks (P = 0.018), 81.3% (13/16) and 37.5% (9/24) at 24 weeks
      (P = 0.006), 93.8% (15/16) and 50.0% (12/24) at 48 weeks (P = 0.004), and 100%
      (16/16) and 54.2% (13/24) at 96 weeks (P = 0.001). Complete response occurred in
      41.7% (5/12) of HBeAg-positive patients in the TDF group and 28.6% (6/21) of the
      LMV group at 96 weeks (P = 0.443). CONCLUSION: TDF monotherapy for 96 weeks
      produced a significantly more effective virologic response than LMV monotherapy
      in children with nucleos(t)ide-naive CHB.

PMID- 29215821
TI  - A Fast 3-Dimensional Magnetic Resonance Imaging Reconstruction for Surgical
      Planning of Uterine Myomectomy.
AB  - BACKGROUND: Uterine myoma is the most common benign gynecologic tumor in
      reproductive-aged women. During myomectomy for women who want to preserve
      fertility, it is advisable to detect and remove all myomas to decrease the risk
      of additional surgery. However, finding myomas during surgery is often
      challenging, especially for deep-seated myomas. Therefore, three-dimensional (3D)
      preoperative localization of myomas can be helpful for the surgical planning for
      myomectomy. However, the previously reported manual 3D segmenting method takes
      too much time and effort for clinical use. The objective of this study was to
      propose a new method of rapid 3D visualization of uterine myoma using a uterine
      template. METHODS: Magnetic resonance images were listed according to the slide
      spacing on each plane of the multiplanar reconstruction, and images that were
      determined to be myomas were selected by simply scrolling the mouse down. By
      using the selected images, a 3D grid with a slide spacing interval was
      constructed and filled on its plane and finally registered to a uterine template.
      RESULTS: The location of multiple myomas in the uterus was visualized in 3D and
      this proposed method is over 95% faster than the existing manual-segmentation
      method. Not only the size and location of the myomas, but also the shortest
      distance between the uterine surface and the myomas, can be calculated. This
      technique also enables the surgeon to know the number of total, removed, and
      remaining myomas on the 3D image. CONCLUSION: This proposed 3D reconstruction
      method with a uterine template enables faster 3D visualization of myomas.

PMID- 29215822
TI  - Eleven-year Cumulative Incidence and Estimated Lifetime Prevalence of
      Urolithiasis in Korea: a National Health Insurance Service-National Sample Cohort
      Based Study.
AB  - BACKGROUND: The purpose of this study was estimation of the cumulative incidence
      and lifetime prevalence of urolithiasis in Korea. METHODS: We used a National
      Health Insurance Service (NHIS) sample cohort dataset that included approximately
      1 million individuals from Korea. Data from January 2002 to December 2013 were
      collected. We calculated the annual prevalence, recurrence rate, and estimate
      lifetime prevalence of urolithiasis. Multivariate logistic regression analysis
      was used to identify risk factors associated with urolithiasis. RESULTS: There
      were 57,921 diagnosed urolithiasis cases in the NHIS database over the 11 years
      studied. The annual incidence of urolithiasis increased every year (Poisson
      regression; hazard ratio, 1.025; P < 0.001). Of the patients with urolithiasis,
      21.3% experienced disease recurrence within 5 years. The 11-year cumulative
      incidence was 5.71%, and the incidence in men was higher than that seen in women
      (7.07% vs. 4.34%, respectively). The 11-year cumulative incidence in the 60- to
      69-year-old group (9.08%) was higher than that seen in any other age group. The
      overall standardized lifetime prevalence rate was estimated to be 11.5%: 12.9% in
      men and 9.8% in women. Meanwhile, age (> 60 years), income level, diabetes, body
      mass index, hypertension, and cancer history were identified as contributing
      factors to urolithiasis. CONCLUSION: This study demonstrates that the annual
      incidence of urolithiasis in Korea is increasing. The overall standardized
      lifetime prevalence rate was higher than that reported in a previous report. This
      study is significant in that it is the first retrospective cohort study to
      estimate the lifetime prevalence of urolithiasis using a large national
      retrospective cohort.

PMID- 29215825
TI  - EMS Vs. Police Transport: Should we allow police officers to transport trauma
      patients?

PMID- 29215824
TI  - Pulmonary Histoplasmosis Identified by Video-Assisted Thoracic Surgery (VATS)
      Biopsy: a Case Report.
AB  - Histoplasmosis is a common endemic mycosis in North, Central, and South America,
      but Korea is not known as an endemic area. We treated an immunocompetent Korean
      patient who had histoplasmosis. A 65-year-old Korean man presented with multiple
      pulmonary clumps of tiny nodules in the both lungs. He had been diagnosed 40
      years earlier with pulmonary tuberculosis (TB) and a fungus ball had been
      diagnosed 4 years earlier. He denied any history of overseas travel. The patient
      visited our hospital with dyspnea, blood-tinged sputum, and weight loss, which
      had appeared 2 months earlier. The patient underwent video-assisted thoracic
      surgery (VATS) lung biopsy. The biopsy sample showed necrotizing granuloma and
      the presence of multiple small yeast-like fungi. Tissue culture confirmed
      Histoplasma capsulatum, and he was finally diagnosed with pulmonary
      histoplasmosis. Therapy was initiated with 200 mg itraconazole orally once per
      day. The symptoms disappeared 1 week after the start of treatment. After 4
      months, low-dose chest computed tomography showed improvement in the ground glass
      opacity and size of the lung lesions. In conclusion, we report a case of an
      immunocompetent patient who developed histoplasmosis in Korea. When a patient
      shows unexplainable progressive infiltrative lung lesions, histoplasmosis should
      be considered as one of differential diagnoses although Korea is not an endemic
      area.

PMID- 29215826
TI  - When is the Need for Speed?

PMID- 29215823
TI  - Validation of the Korean Version of the Scales for Outcomes in Parkinson's
      Disease-Sleep.
AB  - BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease
      (PD), and are associated with a lower quality of life. The aim of the current
      study was to translate the English version of the Scales for Outcomes in
      Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA
      S), and to evaluate its reliability and validity for use by Korean-speaking
      patients with PD. METHODS: In total, 136 patients with PD from 27 movement
      disorder centres of university-affiliated hospitals in Korea were enrolled in
      this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified
      Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd
      version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression
      Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic
      Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep
      Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed
      over a time interval of 10-14 days. RESULTS: The internal consistency (Cronbach's
      alpha-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for
      daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and
      DS, respectively. There was a moderate correlation between the NS sub-score and
      PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with
      motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS,
      NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K
      SCOPA-S exhibited good reliability and validity for the assessment of sleep
      problems in the Korean patients with PD.

PMID- 29215827
TI  - No Need for Speed: Response and transport with red lights and siren.

PMID- 29215828
TI  - From the Operating Room to the Streets: A comprehensive review of the most
      versatile item in your drug box.

PMID- 29215829
TI  - [Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends
      lifespan of mice with experimental carcinoma].
AB  - Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype
      transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on
      the development of Ehrlich carcinoma (EC) in vitro and in vivo. Methods. Tumor
      growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium
      and in vivo by intraperitoneal of EC cell injection into mice. Results. It was
      found that M1-STAT3/6- SMAD3 macrophages have a pronounced anti-tumor effect in
      vitro, and in vivo, which was greater than anti-tumor effects of M1, M1-STAT 3/6,
      M1-SMAD3 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited
      STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify
      the development of new anti-tumor cell therapy technology.

PMID- 29215830
TI  - [Study of migration and distribution of bone marrow cells transplanted animals
      with B16 melanoma ].
AB  - Purpose. Reveal features migration and distribution of syngeneic bone marrow
      cells (BMC) and subpopulations (MSC) after transplantation into the recipient
      carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice.
      Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right
      hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration
      study in vivo distribution and BMC and MSC was performed using genetic markers -
      Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous
      transplantation in females using the polymerase chain reaction (PCR) in real time
      on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction
      suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to
      recipient male mice (syngeneic recipient female C57BL/6), followed by isolation
      of recipients of organs was performed at regular intervals, then of organ
      recipients isolated DNA. Results. It was shown that bone marrow cells positive
      for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non
      lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to
      the migration of cells from the bone marrow to other organs, there is a way back
      migration of cells from the circulation to the bone marrow. B16 melanoma
      stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found
      that tumor growth enhanced migration of transplanted bone marrow cells, including
      populations of MSCs in the bone marrow. In the early stages of tumor formation
      MSC migration activity higher than the BMC. In the later stages of tumor
      formation undivided population of bone marrow cells migrate to the intense
      swelling compared with a population of MSCs. Conclusion. The possibility of using
      bone marrow MSCs for targeted therapy of tumor diseases, because migration of
      MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

PMID- 29215831
TI  - Evaluating Research: Seven essential questions to evaluate clinical research.

PMID- 29215832
TI  - [Activation of regeneration of red and white pulp of the spleen after the
      combined transplantation of HSC and MSCS in terms of exposure to ionizing
      radiation].
AB  - The purpose of this work was to study the effect of combined transplantation of
      multipotent mesenchymal stromal (MSCS) and hematopoietic stem cells (HSCs)
      isolated from the placenta, on the regeneration of white and red pulp of the
      spleen under physiological conditions and in conditions of exposure to ionizing
      radiation. Methods. The experiments were performed with laboratory mice-males. We
      studied the influence of ionizing radiation dose of 4.0 Gy. Animals of the
      experimental group were intravenously infused into MMSC and GSK respectively at a
      dose of 6 million cells/kg and 330 thousand cells/kg, suspended in 0.2 ml of 0.9%
      NaCl solution. The selection of hematopoietic stem cells was carried out using
      the direct technique of immune magnetic separation. Were studied the following
      morphometric parameters of the spleen: the average area of lymphoid follicles,
      the average area of zone of lymphoid follicles, average size of germinal center
      of lymphoid follicles, average size T-zones of lymphoid follicles, the average
      distance between the centers of the follicles, the average cellularity of the red
      pulp. Results. As a result, of research obtained that after exposure to ionizing
      radiation on the background of combined transplantation of HSC and MSCS there is
      an increase in size of lymphoid follicle at the expense of area B-zone of the
      follicle, the area germinative center of the follicle, restoring the content of
      lymphoblasts and lymphoblasts and lymphocytes to normal values. On the background
      of transplantation MMSC and GSK in terms of radiation exposure changes and the
      red pulp of the spleen. The increase in the density of cells in the red pulp of
      the spleen and, as a consequence, of the increase of the distance between the
      centers of lymphoid follicles. The increase in the density of cells in the red
      pulp occurs due to the increase in the content of erythroid cells and by
      increasing granulocytes. Key words: ionizing radiation, multipotent mesenchymal
      stromal cells, hematopoietic stem cells, spleen, regeneration. Conclusion.
      Studies have shown the effectiveness of combined transplantation MSC and GSK in
      respect of the main morphometric parameters of the spleen after exposure to
      ionizing radiation.

PMID- 29215833
TI  - [Effect of conditioned medium from mesenchymal stem cells on regeneration of
      endothelium at HCl-induced damage trachea in rats].
AB  - The purpose. Respiratory epithelium regeneration is studied in rats with tracheal
      damage induced by inhaling hydrochloric acid vapor. Method. Regeneration process
      after the chemical burn was activated by intratracheal administration of
      preparations obtained from the same-species mesenchymal stem cells (MSC).
      Results. Tracheal epithelium is shown to recover almost completely on day 3-7
      after applying MSC compositions (MSCs). Closed structures containing ciliated
      cells similar to ciliated cells of the respiratory epithelium lining the trachea
      are formed in the submucosal epithelium during regeneration. These structures
      migrate towards epithelium and get incorporated into the damaged epithelium. This
      phenomenon is apparently indicative of the special mechanism of respiratory
      epithelium regeneration after HCl-induced injury. Conclusion. It is demonstrated
      in this study that cell-free MSCs instilled intratracheally promote the recovery
      of normal submucosal epithelium by either preventing or reducing necrosis and
      inflammation. Such topical MSCs administration significantly accelerates
      migration of ciliated cell towards the surface and de novo formation of the
      ciliary epithelium.

PMID- 29215834
TI  - A United Response: Programs in Israel and Jersey City, N.J., shift the paradigm
      of the community's role in medical response and disaster preparedness.

PMID- 29215835
TI  - [Matrix metalloproteinase-1, -8, -9 and the risk of cardiovascular complications
      in patients with CHD before and after myocardial revascularization].
AB  - There is still a great need for detection of biomarkers for early prediction and
      diagnosis of cardiovascular complications (CVC) in patients with CHD. Objective:
      To determine the role of MMP-1, 8, 9 in the risk of CCO in patients with CHD
      before and after coronary artery bypass grafting (CABG). Methods. The study
      included 75 patients with coronary heart disease before and after myocardial
      revascularization by CABG, including 40 men and 35 women aged from 45 to 74
      years. Patients were divided into two groups: I group - 25 patients with CVC
      registered after CABG (acute myocardial infarction, ischemic stroke, pulmonary
      thromboembolism Branch); II group - 50 patients with coronary heart disease
      without complications after myocardial revascularization. Blood sampling was
      performed the day before surgery, on the 1st, 3rd and 10th days after CABG.
      Determining the level of MMP-1, 8, 9 in the serum was performed by ELISA using
      reagents specific "RD Diagnostics Inc.", USA. Results are expressed in ng/ml.
      Data are presented as medians and quartiles of two (Me, Q25, Q75). Within and
      between-group differences were evaluated using the Mann - Whitney, Spearman
      correlation coefficient and c2 test within the application program SPSS No16.
      Statistically significant differences between the indicators considered when you
      reject the hypothesis and significance level of p<0,05. Results. A statistically
      increased concentration of MMP-1 and MMP-8 in patients in group I.  Undetermined
      significant dynamics of MMP-9 in patients after myocardial revascularization.
      Conclusion. The results indicate that the level of MMP-1, 2.5 ng/ml or more in
      patients with CAD is a diagnostic criterion for the risk of TE complications. No
      association between high content of MMP-8 and the presence of complications in
      patients after surgery. There were no significant dynamics of MMP-9 in patients
      after myocardial revascularization.

PMID- 29215837
TI  - A New Tradition: Nurse practitioner unit helps L.A. Fire Department meet
      increased demand.

PMID- 29215838
TI  - [Effekt of blood flow shutdown on the vein damage when exposed to HIFU].
AB  - The purpose. In the study we investigated the impact of the partial blood flow
      shutdown on structural changes in the rabbit vena cava posterior wall after
      exposure to high-intensity focused ultrasound (HIFU). Methods. Ultrasound
      Exposure: frequency of 1.65 MHz, the ultrasound intensity in the focus of 13.6
      kW/cm2, the area of the focal spot 1 mm2, continuous ultrasound, exposure for 3
      seconds. Results. Immediately after HIFU exposure all layers of the vein wall
      showed characteristic signs of thermal damage. A week after exposure structural
      changes in the intima, media and adventitia was minimal in the part of vessel
      with preserved blood flow, and after 4 weeks the changes were not revealed. A
      week after HIFU exposure partial endothelium destruction, destruction of
      myocytes, disorganization and consolidation of collagen fibers of the adventitia
      were observed in an isolated segment of the vessel, and in 4 weeks endothelium
      restored and signs of damage in media and adventitia persisted, but were less
      obvious than in a week after exposure. Conclusion. The shutdown of blood flow
      after exposure to HIFU promotes persistent changes in the vein wall. Vein
      compression appears to be necessary for the obliteration of the vessel, when
      using HIFU-technology.

PMID- 29215839
TI  - [Interaction of epinephrine and ADP in regulation of platelet function in chronic
      cerebral ischemia ].
AB  - The purpose is devoted to test of hypothesis that patients with chronic cerebral
      ischemia (CCI) have decreased secretion of platelet ADP as the reason of platelet
      aggregation restriction in response to stimulation of adrenaline. Methods. We
      used platelet-rich plasma which was separated by centrifugation from peripheral
      blood of 55 patients with a diagnosis of CCI of stage 1-2. Platelets aggregation
      was studied on aggregometer Chrono - Log (USA). ADP and Epinephrine were used for
      platelet stimulation at effective concentration (EC50). Modulatory role of ADP
      subthreshold doses (0.5 mM) in platelet activation was analyzed with its addition
      to a suspension of platelets stimulated by agonists (EC50). Results. In 35
      patients (group 1) with platelet hyperreactivity to ADP (EC50) response of
      platelets to Epinephrine was heterogeneous: in 17 cases (48.6%) there was high
      response (50%) and in 18 cases (51.4%) there was low platelet response to
      Epinephrine. 20 patients (group 2) had hyporesponsiveness of platelets upon
      stimulation by both agonists. It was established that the low initial response of
      platelets to Epinephrine in vitro might be due to reduced secretion of ADP, i.e.
      limited adaptive response since administration of ADP subthreshold doses enhances
      adrenoreactivity of platelets. If pathochemical violations underlying the
      formation of platelet disadaptation are reversible, it is possible to recover the
      reaction of platelets to Epinephrine. Conclusion. In reducing the functional
      response of platelets to Epinephrine key issue is establishing the reversibility
      of violations of platelets adaptive response of platelets.

PMID- 29215840
TI  - Rethinking Naloxone: Overdose drug is only one part of the cycle of narcotic
      abuse.

PMID- 29215842
TI  - Hands On: Product Reviews From Street Crews.

PMID- 29215841
TI  - [Histamine metabolism disorder in pathogenesis of chronic pelvic pain in patients
      with external genital endometriosis].
AB  - Objective. To study features of histamine metabolism in patients with chronic
      pelvic pain associated with external genital endometriosis. Methods. For
      quantitative assessment of histamine level in peripheral blood was taken from 100
      patients which than was centrifuged. In blood serum histamine concentration was
      determined by enzyme-linked immunosorbent assay method with reagents "Histamine
      ELISA" on the machine BAE-1000 Histamine (Labor Diagnostika Nord - LDN, Hermany).
      A pain syndrome was assessed by Visual Analog Scale (VAS), quality of life
      assessment - by Endometriosis Health Profile Questionnaire (EHR-30), level of
      anxiety was determined by Spielberger-Khanin questionnaire. The results. Showed
      statistically higher histamine level in patients with severe pain according to
      VAS. After assessment of results obtained from Spielberger-Khanin questionnaire
      100% experimental group's women with external genital endometriosis (n = 60) were
      noted to be have high level of state and trait anxiety, then 40% women of control
      group (n = 16) have moderate level of anxiety. The incidence of depression in
      women with chronic pelvic pain was 58.3% (n = 35) and the main part (n = 20) were
      women with severe stage of pelvic pain according to VAS. Conclusions. Psycho
      emotional condition of women with external genital endometriosis associated
      pelvic pain characterized by higher depression and anxiety levels, with
      significant decrease quality of life. Direct relationship also was found between
      pain syndrome intensity and histamine level in peripheral blood in patients with
      external genital endometriosis.

PMID- 29215843
TI  - [Influence of partial hepatectomie on ammoniumdetoxications function of liver at
      chronic tetrachlorcarbon hepatitis].
AB  - The purpose. To study the effect of partial hepatectomy (PH) on the main ways of
      ammonia detoxication in the liver (synthesis of urea and glutamine) in chronic
      tetrachlorcarbon (CCl4) hepatitis. Methods. The experiments were performed on 165
      white outbred rats (females) weighing 180-220 g Chronic CCl4-hepatitis was
      reproduced by subcutaneous injection of 50% CCl4 solution in olive oil (0.1
      ml/100g of body weight,65 days, through the day with two two-week breaks between
      6-7 and 13-14 injections). PH conducted electrocautery, removing part of the left
      lobe of the liver (15-20% by weight of the body) to 65th (and last) day of the
      introduction of the CCl4. Animals were studied after 65 days of development of
      CCl4-hepatitis on day 3, 7 and 14 days after laparotomy ("falsely operated"
      animals) and partial hepatectomy. In subcellular fractions of the liver
      investigated the activity of phosphatdependent glutaminase (FDG),
      glutamatdehydrogenaze (GDG), glutaminsintetaze (GS), arginase. In the liver
      tissue investigated the content of ammonia, glutamine, glutamate and urea.
      Results. Found that on 65-th day of the development of CCl4 in the liver
      decreases the concentration of ammonia, glutamine, glutamate, urea, and activity
      of GS, GDG and arginase. Activity FDG was not changed. The use of PH on the
      background of chronic CCl4-hepatitis has a short-term (3 days) a stimulating
      effect on the activity FDG, GS, postponed (14 days) the inhibitory effect on the
      activity of GDG. This was accompanied by an increase in the concentration in the
      liver of ammonia within 14 days of the postoperative period on the background of
      maintaining reduced concentrations of glutamine and glutamate it. The stimulatory
      effect of CHA on the activity of arginase is saved to the 14th day of the
      postoperative period, however, the concentration of urea in the liver remained
      below normal. Conclusions. The obtained results show that CGA on the background
      of chronic hepatitis increases the pathological impact of CCl4 on amniocentesis
      liver function.

PMID- 29215844
TI  - [Exposure to toxic dose of adrenaline on the functional state of the liver].
AB  - The purpose: The blood biochemical parameters characterizing the functional state
      of the liver, and the morphological profile of the body after a single exposure
      to a toxic dose of adrenaline were studied. Methods: Studies were conducted on 60
      adult rats (female) weighing 0.15-0.2 kg, were divided into groups: intact
      animals; experience - animals, injected with epinephrine hydrochloride
      intraperitoneally in a dose of 0.5 mg/kg.  All kinds of Biological material
      (blood, liver) were collected out through one and ten days after the start of the
      experiment.  The degree of influence of high doses of epinephrine were evaluated
      in terms of lipid peroxidation (LPO) and protein (PSP) in liver homogenates, the
      concentration of average weight molecules (MSM), the activity of ALT, AST,
      alkaline phosphatase, LDH, total protein concentration, glucose and lactate in
      the blood plasma, as well as the determination of the prothrombin time (PTT) with
      the counting on the basis thereof of international normalized ration (INR). 
      Histology of the liver was studied by light microscopy. Results: It was found
      that throughout the experiment, there was an increased in the concentration of
      lipid peroxidation products and protein in liver homogenates, there was an
      increase in the concentration of MSM 1.7.  Twenty-four hours after the
      administration of a toxic dose of adrenaline observed hyperenzymemia that
      manifested an increase in the activity of ALT and AST, was an increase in LDH. 
      After 10-day five after the start of the experiment established the presence
      hyperenzymemia activity decreased ALT and AST, LDH activity remained elevated,
      total protein level was higher than in the group of animal in which
      investigations were conducted one day after the start of the experiment, PTV also
      continued to decline.  In histological sections of the development of a
      pathological condition characterized by circulatory disturbance - plasmatization,
      both in central and in small vessels.  From the hepatocytes both in the center
      and the periphery had changes granular dystrophy type, to some extent vacuolar.

PMID- 29215845
TI  - #Millennials: A baby boomer compromises with Gen Y.

PMID- 29215846
TI  - [Possibilities of correction rheological blood svoytv at chipped and cut wounds
      of the breast ].
AB  - The purpose: research objective: to study influence of electromagnetic
      oscillations of millimetric range on rheological properties of blood at patients
      with chipped and cut wounds of a breast for the purpose of their correction.
      Methods. For the solution of a research objective we have carried out studying of
      changes of rheological properties of blood at the 22nd patient with the getting
      chipped and cut wounds of a breast without internal injury during the next
      postoperative period. All patient has executed primary surgical processing and
      drainage of a pleural cavity. At all patients the volume of blood loss has made
      200-500 ml. Criteria of inclusion were: existence of the getting wound of a
      thorax, existence of a small gemotoraks. Criteria of an exception: blood loss
      existence more than 500 ml, existence of the combined and multiple damages. The
      main group is divided into two subgroups, in the first 12 patients with
      application of electromagnetic oscillations of millimetric range, have entered
      the second 10 people without application of electromagnetic oscillations of
      millimetric range. The group of comparison was made by 15 rather healthy donor
      volunteers of the same age and a floor. To all patients the hemotransfusion
      wasn't carried out, the volume of infusional therapy was comparable in both
      groups. Changes of a rheology of blood came to light by means of the accounting
      of viscosity of blood, change of an index of deformation and aggregation of
      erythrocytes. Conclusion. As a result of the conducted research it is established
      that application of electromagnetic oscillation of millimetric range for patients
      with chipped and cut wounds of a breast prevents development of changes of
      rheological properties of blood, at the same time patients well transfer this
      procedure that is shown by lack of side effects.

PMID- 29215847
TI  - [Pathogenic peculiarities of disseminated intravascular coagulation of various
      ethiology].
AB  - DIC is a severe complication, often resulting in multi-organ failure and fatal
      outcome. As any syndrome, it is polyethiologic, while a big number of its causes
      logically leads to various mechanisms of its forming. Main manifestations of the
      disseminated intravascular blood coagulation syndrome are clottage and
      haemorrhage. A result of a massive clottage in microcirculatory bed of internal
      organs is development of dystrophic changes in them and organ failure.
      Haemorrhage in its turn, results in decreased volume of circulating blood,
      arterial hypotension and hemic hypoxia, in most severe cases leading to the fatal
      outcome. Although, development mechanisms and manifestation degree of the
      disorder mentioned above are not always the same. As the syndrome may result from
      a great number of causes (currently, over 150 diseases have been described with
      which it can develop), namely its initial stages are different to the greatest
      extent. Main triggering mechanisms of the DIC may be: blood formed element
      activation and increased process of their microvesiculation, activation of
      coagulative hemostasis in intrinsic and extrinsic pathways, lack of
      anticoagulants and excessive activity of fibrinolytic system. Various ethiologic
      factors (sepsis, obstetrical pathology, leucosis and other malignant tumours,
      traumas, etc) have different effect on function of hemostasis system components.
      Depending on the degree of the above mentioned disorders mechanisms
      manifestation, the DIC may develop with prevailing coagulation, with prevailing
      fibrinolysis or with their balanced activation. Clinical manifestations of these
      DIC forms, as well as duration and manifestation degree of its stages
      (hypercoagulation, coagulopathy of consumption with compensatory activation of
      fibrinolysis, defibrination of the blood and excessive activation of
      fibrinolysis) will be different as well. Consequently, knowing the prevailing
      disorder in hemostasis system during a disease that is potentially dangerous in
      terms of the DIC development offers to find optimal methods of its prevention,
      diagnosing and treatment.

PMID- 29215848
TI  - [Molecular biology of brain meningiomas].
AB  - Meningiomas are by far the most common tumors arising from the minges.  A myriad
      of aberrant signaling pathways involved with meningioma tumorigenesis, have been
      discovered.  Understanding these disrupted pathways will aid in deciphering the
      relationship between various genetic changes and their downstream effects on
      meningioma pathogenesis.  An understanding of the genetic and molecular profile
      of meningioma would provide a valuable first step towards developing more
      effective treatment for this intracranial tumor.  Chromosomes 1, 10, 14, 22,
      their associated genes, have been linked to meningioma proliferation and
      progression.  It is presumed that through an understanding of these genetic
      factors, more educated meningioma treatment techniques can be implemented. 
      Future therapies will include combinations of targeted molecular agents including
      gene therapy, si-RNA mediation, proton therapy, and other approaches as a result
      of continued progress in the understanding of genetic and biological changes
      associated with meningiomas.

PMID- 29215849
TI  - [Study of mitochondrial dysfunction using cytoplasmic hybrid].
AB  - Aim. This review article describes literature sources devoted to the
      investigation of mitochondrial dysfunction using cytoplasmic hybrids (cybrids).
      The presented studies were carried out on cultures of cybrid cell lines HL60, MOL
      T-4, A549, 143B, HeLa, Arpe-19, HEK-293, SH-SY5Y and NT2. According to the
      analysis of scientific world literature, some of the most promising models for
      studying mitochondrial dysfunction are cell cultures without mitochondria (rho0)
      and cytoplasmic hybrids containing one or several mutations of mitochondrial
      genome. In the review scientific researches on studying biochemical and molecular
      cellular pathological processes in cybrid cells in various human diseases such as
      Alzheimer's disease and mild cognitive impairment, MERRF and MELAS syndromes,
      Leber's optic atrophy and Parkinson's disease were considered. Material dedicated
      to cybrids as potential models for the study of treatment possibilities was
      presented separately. Conclusion. The analyzed in the review rho0-cell cultures
      and cybrid lines containing mtDNA mutations may be models for the study of
      mitochondrial genome dysfunctions, biochemical and molecular cellular
      pathological processes. It is worth noting that in various cell cultures, similar
      tendencies are observed in functional activity changes of rho0-cell and cybrids
      compared with native cell lines. For example, such tendencies as reduction of
      oxygen consumption level, morphological changes of mitochondrial structure,
      resistance to apoptosis, reduction of ATP consumption level, increase in glucose
      consumption, activity deterioration of some respiratory chain complexes.

PMID- 29215850
TI  - [The role of prostaglandins and Cyclooxygenase in pathogenesis of chronic
      endometritis].
AB  - The purpose: to present the modern data of cyclooxygenase role (COX) in the
      development of chronic endometritis.106 references on the role of COX-1 and COX-2
      in the development of chronic endometritis in patients of reproductive age,
      published in the Medline database, Pubmed, Scopus were analyzed; 14 sources are
      included in this review. Prostaglandins (PG) play an important role in
      maintaining inflammatory process in the endometrium. Nevertheless, the production
      of PG and leukotrienes (LTS) - lipid mediators, which, along with PG, play a
      major role in the inflammatory process of the inflamed uterus, is not fully
      understood. Cyclooxygenase-2, the enzyme having various physiological functions,
      is involved in reproduction, where its role is polyfunctional. It has been
      established that the inhibition of cyclooxygenase pathways, blocking the
      synthesis of prostaglandins, eliminates the effects of many pro-inflammatory
      cytokine involved in the pathogenesis of chronic endometritis. Conclusion. The
      role of cyclooxygenase in the development of chronic endometritis is interesting;
      on the basis of the acquired knowledge, we can plan the use of drugs that inhibit
      the cyclooxygenase pathway (NSAIDs) in the treatment of chronic endometritis - as
      a method of pathogenetic therapy. The issue is not fully understood. Further
      research is needed in this sphere.

PMID- 29215851
TI  - [Monitoring of brightness temperature fluctuation of water in SHF range].
AB  - The purpose of the research consisted in detection of fluctuation of brightness
      temperature (TSHF) of water in the area of the temperature T = 42 degrees S (that
      is critical for human) during its evaporation by SHF radiometry. Methods:
      Monitoring of the changes in brightness temperature of water in superhigh
      frequency (SHF) range (3.8-4.2 GHz) near the phase transition temperature of
      water T = 42 degrees S during its evaporation in the cone dielectric cell. The
      brightness temperature measurements were carried out using radiometer. Results:
      Fluctuation with maximum of brightness temperature was detected in 3.8-4.2 GHz
      frequency range near at the temperature of water T = 42 degrees S. It was
      characteristic for these TSHF fluctuations that brightness temperature rise time
      in this range of frequencies in ~4 degrees S temperature range with 0.05-15
      degrees S/min gradient and a sharp decrease during 10 s connected with measuring
      vapor conditions. Then nonintensive fluctuation series was observed. At that, the
      environment temperature remained constant. Conclusion: The significant increasing
      in brightness temperature of water during its evaporation in SHF range near the
      temperature of T ~42 degrees S were detected. It was shown that for water, TSHF
      pull with the amplitude DTSHF ~4 degrees C are observed. At the same time,
      thermodynamic temperature virtually does not change. The observed effects can be
      used in the development of the systems for diadnostics of pathologies in human
      and analytical system.

PMID- 29215852
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29215858
TI  - Liraglutide and Renal Outcomes in Type 2 Diabetes.

PMID- 29215859
TI  - Mining Plants for Bacterial Quorum Sensing Modulators.
AB  - The bacterial plant pathogen Agrobacterium tumefaciens uses quorum sensing (QS)
      in order to regulate the transfer of DNA into the host plant genome, and this
      results in the induction of crown gall tumors. The deleterious results of these
      infections are widespread and affect many species of fruit and crops. In order to
      further our understanding of this process and to provide potential solutions, we
      evaluated a library of 3800 natural products from plant sources and identified
      potent compounds that are able to strongly modulate plant-bacterial interactions.

PMID- 29215860
TI  - Direct Measurement of Single-Molecule Adenosine Triphosphatase Hydrolysis
      Dynamics.
AB  - F1-ATPase (F1) is a bidirectional molecular motor that hydrolyzes nearly all ATPs
      to fuel the cellular processes. Optical observation of labeled F1 rotation
      against the alpha3beta3 hexamer ring revealed the sequential mechanical rotation
      steps corresponding to ATP binding/ADP release and ATP hydrolysis/Pi release.
      These substeps originate from the F1 rotation but with heavy load on the gamma
      shaft due to fluorescent labeling and the photophysical limitation of an optical
      microscope, which hampers better understanding of the intrinsic kinetic behavior
      of ATP hydrolysis. In this work, we present a method capable of electrically
      monitoring ATP hydrolysis of a single label-free F1 in real time by using a high
      gain silicon nanowire-based field-effect transistor circuit. We reproducibly
      observe the regular current signal fluctuations with two distinct levels, which
      are induced by the binding dwell and the catalytic dwell, respectively, in both
      concentration- and temperature-dependent experiments. In comparison with labeled
      F1, the hydrolysis rate of nonlabeled F1 used in this study is 1 order of
      magnitude faster (1.69 * 108 M-1 s-1 at 20  degrees C), and the differences
      between two sequential catalytic rates are clearer, demonstrating the ability of
      nanowire nanocircuits to directly probe the intrinsic dynamic processes of the
      biological activities with single-molecule/single-event sensitivity. This
      approach is complementary to traditional optical methods, offering endless
      opportunities to unravel molecular mechanisms of a variety of dynamic biosystems
      under realistic physiological conditions.

PMID- 29215861
TI  - Photoinduced Field-Effect Passivation from Negative Carrier Accumulation for High
      Efficiency Silicon/Organic Heterojunction Solar Cells.
AB  - Carrier recombination and light management of the dopant-free silicon/organic
      heterojunction solar cells (HSCs) based on poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are the critical
      factors in developing high-efficiency photovoltaic devices. However, the
      traditional passivation technologies can hardly provide efficient surface
      passivation on the front surface of Si. In this study, a photoinduced electric
      field was induced in a bilayer antireflective coating (ARC) of
      polydimethylsiloxane (PDMS) and titanium oxide (TiO2) films, due to formation of
      an accumulation layer of negative carriers (O2- species) under UV (sunlight)
      illumination. This photoinduced field not only suppressed the silicon surface
      recombination but also enhanced the built-in potential of HSCs with 84 mV
      increment. In addition, this photoactive ARC also displayed the outstanding light
      trapping capability. The front PEDOT:PSS/Si HSC with the saturated O2- received a
      champion PCE of 15.51% under AM 1.5 simulated sunlight illumination. It was
      clearly demonstrated that the photoinduced electric field was a simple,
      efficient, and low-cost method for the surface passivation and contributed to
      achieve a high efficiency when applied in the Si/PEDOT:PSS HSCs.

PMID- 29215862
TI  - Reticular Chemistry and the Discovery of a New Family of Rare Earth (4, 8)
      Connected Metal-Organic Frameworks with csq Topology Based on RE4(MU3-O)2(COO)8
      Clusters.
AB  - In recent years, the design and discovery of new metal-organic framework (MOF)
      platforms with distinct structural features and tunable chemical composition has
      remarkably enhanced by applying reticular chemistry rules and the molecular
      building block (MBB) approach. We targeted the synthesis of new rare earth (RE)
      MOF platforms based on a rectangular-shaped 4-c linker, acting as a rigid organic
      MBB. Accordingly, we designed and synthesized the organic ligand 1,2,4,5
      tetrakis(4-carboxyphenyl)-3,6-dimethyl-benzene (H4L), in which the two methyl
      groups attached to the central phenyl ring lock the four peripheral carboxyphenyl
      groups to an orthogonal/vertical position. We report here a new family of RE-MOFs
      featuring the novel inorganic building unit, RE4(MU3-O)2 (RE: Y3+, Tb3+, Dy3+,
      Ho3+, Er3+, and Yb3+), with planar D2h symmetry. The rigid 4-c linker, H4L,
      directs the in situ assembly of the unique 8-c RE4(MU3-O)2(COO)8 cluster,
      resulting in the formation of the first (4, 8)-c RE-MOFs with csq topology, RE
      csq-MOF-1. The structures of the yttrium (Y-csq-MOF-1) and holmium (Ho-csq-MOF-1)
      analogues were determined by single-crystal X-ray diffraction analysis. Y-csq-MOF
      1 was successfully activated and tested for Xe/Kr separation. The results show
      that Y-csq-MOF-1 has high isosteric heat of adsorption for Xe (33.8 kJ mol-1),
      with high Xe/Kr selectivity (IAST 12.1, Henry 12.9) and good Xe uptake (1.94 mmol
      g-1 at 298 K and 1 bar), placing this MOF among the top-performing adsorbents for
      Xe/Kr separation.

PMID- 29215863
TI  - Near-Infrared Laser-Excited Nanoparticles To Eradicate Multidrug-Resistant
      Bacteria and Promote Wound Healing.
AB  - With the ever-growing threat of bacterial infections, especially for multidrug
      resistant microbial infections, the development of highly effective treatment
      modalities to inhibit the infections is challenging. Although silver
      nanoparticles have been intensively applied as antimicrobial agent for decades,
      the therapeutic efficacy toward multidrug-resistant bacteria is still
      unsatisfactory. Here, we show that near-infrared (NIR) laser-excited silver
      triangular nanoparticles (Tri-Ag) can efficiently kill Gram-negative Escherichia
      coli and Gram-positive Staphylococcus aureus both in vitro and in vivo. Notably,
      multidrug-resistant bacterial clinical isolates, including methicillin-resistant
      S. aureus and extended spectrum beta-lactamase E. coli strain were significantly
      inhibited by the combined treatment of the Tri-Ag with NIR laser irradiation due
      to their synergistic antibacterial ability. Taking the advantage of its strong
      near-infrared absorbance, photothermal treatment is also conducted with Tri-Ag,
      achieving a remarkable synergistic antibacterial effect to inhibit various
      bacteria at a rather low concentration of this agent. Given the above advantages,
      the combination therapy of Tri-Ag with assistance of NIR laser may find potential
      applications to strengthen the antimicrobial arsenal for fighting bacterial
      infections.

PMID- 29215864
TI  - Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral
      Flow Immunoassays with Ultrabroad Dynamic Range.
AB  - Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used
      point-of-care (PoC) devices; however, their application in early disease
      diagnostics is often limited due to insufficient sensitivity for the requisite
      sample sizes and the short time frames of PoC testing. To address this, we
      developed a serum-stable, nanoparticle catalyst-labeled LFIA with a sensitivity
      surpassing that of both current commercial and published sensitivities for paper
      based detection of p24, one of the earliest and most conserved biomarkers of HIV.
      We report the synthesis and characterization of porous platinum core-shell
      nanocatalysts (PtNCs), which show high catalytic activity when exposed to complex
      human blood serum samples. We explored the application of antibody-functionalized
      PtNCs with strategically and orthogonally modified nanobodies with high affinity
      and specificity toward p24 and established the key larger nanoparticle size
      regimes needed for efficient amplification and performance in LFIA. Harnessing
      the catalytic amplification of PtNCs enabled naked-eye detection of p24 spiked
      into sera in the low femtomolar range (ca. 0.8 pg.mL-1) and the detection of
      acute-phase HIV in clinical human plasma samples in under 20 min. This provides a
      versatile absorbance-based and rapid LFIA with sensitivity capable of
      significantly reducing the HIV acute phase detection window. This diagnostic may
      be readily adapted for detection of other biomolecules as an ultrasensitive
      screening tool for infectious and noncommunicable diseases and can be capitalized
      upon in PoC settings for early disease detection.

PMID- 29215865
TI  - Identification of Fluorescent Small Molecule Compounds for Synaptic Labeling by
      Image-Based, High-Content Screening.
AB  - Few tools are available for noninvasive imaging of synapses in the living
      mammalian brain. Current paradigms require the use of genetically modified mice
      or viral delivery of genetic material to the brain. To develop an alternative
      chemical approach, utilizing the recognition of synaptic components by organic
      small molecules, we designed an imaging-based, high-content screen in cultured
      cortical neurons to identify molecules based on their colocalization with
      fluorescently tagged synaptic proteins. We used this approach to screen a library
      of ~7000 novel fluorescent dyes, and identified a series of compounds in the
      xanthone family that exhibited consistent synaptic labeling. Follow-up studies
      with one of these compounds, CX-G3, demonstrated its ability to label acidic
      organelles and in particular synaptic vesicles at glutamatergic synapses in
      cultured neurons and murine brain tissue, indicating the potential of this
      screening approach to identify promising lead compounds for use as synaptic
      markers, sensors, and targeting devices.

PMID- 29215866
TI  - Carbon-Induced Generation of Hierarchical Structured Ni0.75Co0.25(CO3)0.125(OH)2
      for Enhanced Supercapacitor Performance.
AB  - Hierarchical nanostructures with heteroatom doping have been considered as an
      important component in electrode materials for advanced supercapacitors. Herein,
      with the aid of C, N, and S codoped Ni0.75Co0.25(CO3)0.125(OH)2/C (NSH) with a
      hierarchical structure was synthesized through a facile one-step hydrothermal
      method. Notably, it is the first report on a carbon precursor as a structure
      inducer for designing a three-dimensional (3D) carnation-like hierarchical
      structure. Thanks to the carbon induction effect and the introduction of N/S
      dopants, the obtained NSH with a 3D architecture exhibits superior performances
      as electrode materials for supercapacitors. For example, NSH offers a high
      specific capacity of 277.3 mAh/g at 0.5 A/g. Moreover, the assembled NSH//reduced
      graphene oxide hydrogel-based hybrid supercapacitor exhibits high energy
      densities of 44.4 and 11.7 Wh/kg at power densities of 460 W/kg and 9.8 kW/kg,
      respectively. This result opens up opportunities for carbon-induced methods to
      control the morphology and structure of other similar materials.

PMID- 29215868
TI  - Synthesis of pH-Responsive Biodegradable Mesoporous Silica-Calcium Phosphate
      Hybrid Nanoparticles as a High Potential Drug Carrier.
AB  - Biodegradability is one of the most critical issues for silica-based nanodrug
      delivery systems because they are crucial prerequisites for the successful
      translation in clinics. In this work, a novel mesoporous silica-calcium phosphate
      (MS-CAP) hybrid nanocarrier with a fast pH-responsive biodegradation rate was
      developed by a one-step method, where CAP precursors (Ca2+ and PO43-) were
      incorporated into silica matrix during the growth process. The morphology and
      structure of MS-CAP were characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), N2 adsorption-desorption isotherms,
      Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy.
      Furthermore, the drug loading and the release behavior of MS-CAP have been
      tested. TEM and inductively coupled plasma-optical emission spectrometry results
      indicated that the pH-responsive biodegradation of MS-CAP was so fast that could
      be almost finished within 24 h owing to the easy dissolution of CAP embedded in
      the particle and the escape of Ca2+ from the structure of Si-O-Ca in acid
      environment. The MS-CAP exhibited a high doxorubicin (DOX) entrapment efficiency
      (EE) of 97.79%, which was about fourfold higher compared with that of pure
      mesoporous silica nanoparticles, and our density functional theory calculational
      results suggested that the higher drug EE of MS-CAP would originate from the
      strong interaction between calcium in the particle and carboxylate group of DOX.
      The loaded DOX was effectively released, with a cumulative release as high as
      98.06% within 48 h at pH 4.5 in buffer solution, owing to the rapid degradation
      of MS-CAP. The obtained results indicated that the as-synthesized MS-CAP could
      act as a promising drug delivery system and would have a hopeful prospect in the
      clinical translation.

PMID- 29215869
TI  - Combining Multiscale Approaches for the Structure Determination of an Iron
      Layered Oxysulfate: Sr4Fe2.5O7.25(SO4)0.5.
AB  - The new iron layered oxysulfate Sr4Fe2.5O7.25(SO4)0.5 has been prepared by a
      solid-state reaction in closed ampules into the form of ceramics and single
      crystals. Its atomic structure has been solved by means of spectroscopy,
      diffraction techniques, and high-resolution electron microscopy.
      Sr4Fe2.5O7.25(SO4)0.5 is a layered structure that derives from the Ruddelsden
      Popper (RP) phases with the layer stacking sequence
      SrO/SrFeO2.5/SrFe0.5(SO4)0.5O1.25/SrFeO2.5. Within the mixed Fe3+/SO42- layer,
      the sulfur atoms are slightly shifted from the B site of the perovskite and each
      sulfate group shares two corners with iron pyramids in the basal plan without any
      order phenomenon. The electronic conductivity is thermally activated, while no
      ionic conductivity is detected.

PMID- 29215867
TI  - Direct Substrate Identification with an Analog Sensitive (AS) Viral Cyclin
      Dependent Kinase (v-Cdk).
AB  - Viral cyclin-dependent kinases (v-Cdks) functionally emulate their cellular Cdk
      counterparts. Such viral mimicry is an established phenomenon that we extend here
      through chemical genetics. Kinases contain gatekeeper residues that limit the
      size of molecules that can be accommodated within the enzyme active site.
      Mutating gatekeeper residues to smaller amino acids allows larger molecules
      access to the active site. Such mutants can utilize bio-orthoganol ATPs for
      phosphate transfer and are inhibited by compounds ineffective against the wild
      type protein, and thus are referred to as analog-sensitive (AS) kinases. We
      identified the gatekeeper residues of the v-Cdks encoded by Epstein-Barr virus
      (EBV) and human cytomegalovirus (HCMV) and mutated them to generate AS kinases.
      The AS-v-Cdks are functional and utilize different ATP derivatives with a
      specificity closely matching their cellular ortholog, AS-Cdk2. The AS derivative
      of the EBV v-Cdk was used to transfer a thiolated phosphate group to targeted
      proteins which were then purified through covalent capture and identified by mass
      spectrometry. Pathway analysis of these newly identified direct substrates of the
      EBV v-Cdk extends the potential influence of this kinase into all stages of gene
      expression (transcription, splicing, mRNA export, and translation). Our work
      demonstrates the biochemical similarity of the cellular and viral Cdks, as well
      as the utility of AS v-Cdks for substrate identification to increase our
      understanding of both viral infections and Cdk biology.

PMID- 29215870
TI  - Investigation of a Structural Phase Transition and Magnetic Structure of
      Na2BaFe(VO4)2: A Triangular Magnetic Lattice with a Ferromagnetic Ground State.
AB  - The structural and magnetic properties of a glaserite-type Na2BaFe(VO4)2
      compound, featuring a triangular magnetic lattice of Fe2+ (S = 2), are reported.
      Temperature dependent X-ray single crystal studies indicate that at room
      temperature the system adopts a trigonal P3m1 structure and undergoes a
      structural phase transition to a C2/c monoclinic phase slightly below room
      temperature (Ts = 288 K). This structural transition involves a tilting of Fe-O-V
      bond angles and strongly influences the magnetic correlation within the Fe
      triangular lattice. The magnetic susceptibility measurements reveal a
      ferromagnetic transition near 7 K. Single crystal neutron diffraction confirms
      the structural distortion and the ferromagnetic spin ordering in Na2BaFe(VO4)2.
      The magnetic structure of the ordered state is modeled in the magnetic space
      group C2'/c' that implies a ferromagnetic order of the a and c moment components
      and antiferromagnetic arrangement for the b components. Overall, the Fe magnetic
      moments form ferromagnetic layers that are stacked along the c-axis, where the
      spins point along one of the (111) facets of the FeO6 octahedron.

PMID- 29215872
TI  - Selective Nitrate Reduction to Dinitrogen by Electrocatalysis on Nanoscale Iron
      Encapsulated in Mesoporous Carbon.
AB  - Excessive nutrients (N and P) are among the most concerned pollutants in surface
      and ground waters. Herein, we report nanoscale zero-valent iron supported on
      ordered mesoporous carbon (nZVI@OMC) for electrocatalytic reduction of nitrate
      (NO3-) to nitrogen gas (N2). This material has a maximum removal capacity of 315
      mg N/g Fe and nitrogen selectivity up to 74%. The Fe-C nanocomposite is prepared
      via a postsynthetic modification including carbon surface oxidation, in
      situammonia prehydrolysis of iron precursor and hydrogen reduction. The
      synthesized materials have large surface areas (660-830 m2/g) and small iron
      nanoparticles (3-9 nm) uniformly dispersed in the carbon mesochannels. The iron
      loading can be adjusted in the range of 0-45%. Results demonstrate that the
      reaction reactivity of electrocatalysis can be fine-tuned by manipulating iron
      nanoparticle size, degree of crystallization, as well as porous structure.
      Meanwhile, the small, uniform, and stable iron nanoparticle promotes fast
      hydrogen generation for rapid cleavage of the N-O bond. Furthermore, this
      material can maintain its high performance over repetitive experimental cycles.
      Results suggest a new approach for fast and eco-friendly nitrate reduction and a
      novel nZVI application.

PMID- 29215871
TI  - MPA Portable: A Stand-Alone Software Package for Analyzing Metaproteome Samples
      on the Go.
AB  - Metaproteomics, the mass spectrometry-based analysis of proteins from
      multispecies samples faces severe challenges concerning data analysis and results
      interpretation. To overcome these shortcomings, we here introduce the
      MetaProteomeAnalyzer (MPA) Portable software. In contrast to the original server
      based MPA application, this newly developed tool no longer requires computational
      expertise for installation and is now independent of any relational database
      system. In addition, MPA Portable now supports state-of-the-art database search
      engines and a convenient command line interface for high-performance data
      processing tasks. While search engine results can easily be combined to increase
      the protein identification yield, an additional two-step workflow is implemented
      to provide sufficient analysis resolution for further postprocessing steps, such
      as protein grouping as well as taxonomic and functional annotation. Our new
      application has been developed with a focus on intuitive usability, adherence to
      data standards, and adaptation to Web-based workflow platforms. The open source
      software package can be found at https://github.com/compomics/meta-proteome
      analyzer .

PMID- 29215873
TI  - Novel Multicomponent Synthesis of Pyridine-Pyrimidines and Their Bis-Derivatives
      Catalyzed by Triazine Diphosphonium Hydrogen Sulfate Ionic Liquid Supported on
      Functionalized Nanosilica.
AB  - In this Research Article, we report an efficient synthesis of 1,3-dimethyl-5-aryl
      7-(pyridine-3(2)(4)-yl)pyrimidine-2,4(1H,3H)-diones via a three-component
      reaction of aryl aldehydes, 1,3-dimethyl-6-aminouracil and carbonitriles in the
      presences of triazine diphosphonium hydrogen sulfate ionic liquid supported on
      functionalized nanosilica (APTADPHS-nSiO2) as a reusable catalyst under microwave
      irradiation and solvent-free conditions. The bis-derivatives of pyridine
      pyrimidines were also efficiently prepared from dialdehydes and dinitriles. In
      addition, 3-methyl-1H-pyrazole-5-amine was used successfully instead of 1,3
      dimethyl-6-aminouracil under the same conditions to afford the corresponding
      products in high yields. The catalyst can be reused at least five times without
      any significant loss of its activity. The easy recovery, reusability and
      excellent activity of the catalyst as well as easy workup are other noteworthy
      advantages of this method.

PMID- 29215874
TI  - Influence of Magnetite Stoichiometry on the Binding of Emerging Organic
      Contaminants.
AB  - While the magnetite stoichiometry (i.e., Fe(II)/Fe(III) ratio) has been
      extensively studied for the reductive transformation of chlorinated or
      nitroaromatic compounds, no work exists examining the influence of stoichiometry
      of magnetite on its binding properties. This study, for the first time,
      demonstrates that the stoichiometry strongly affects the capacity of magnetite to
      bind not only quinolone antibiotics such as nalidixic acid (NA) and flumequine
      (FLU), but also salicylic acid (SA), natural organic matter (humic acid, HA), and
      dissolved silicates. Fe(II)-amendment of nonstoichiometric magnetite
      (Fe(II)/Fe(III) = 0.40) led to similar sorbed amounts of NA, FLU, SA, silicates
      or HA as compared to the stoichiometric magnetite (i.e., Fe(II)/Fe(III) = 0.50).
      At any pH between 6 and 10, all magnetites exhibiting similar Fe(II)/Fe(III)
      ratio in the solid phase showed similar adsorption properties for NA or FLU. This
      enhancement in binding capability of magnetite for NA is still observed in the
      presence of environmentally relevant ligands (e.g., 10 mg L-1 of HA or 100 MUM of
      silicates). Using surface complexation modeling, it was shown that the NA
      magnetite complexation constant does not vary with Fe(II)/Fe(III) between 0.24
      and 0.40, but increases by 8 orders of magnitude when Fe(II)/Fe(III) increases
      from 0.40 to 0.50.

PMID- 29215875
TI  - A "Nanopore Lithography" Strategy for Synthesizing Hierarchically
      Micro/Mesoporous Carbons from ZIF-8/Graphene Oxide Hybrids for Electrochemical
      Energy Storage.
AB  - Porous carbons derived from metal-organic frameworks (MOFs) are promising
      materials for a number of energy- and environment-related applications, but their
      almost exclusively microporous texture can be an obstacle to their performance in
      practical uses. Here, we introduce a novel strategy for the generation of very
      uniform mesoporosity in a prototypical MOF, namely, zeolitic imidazolate
      framework-8 (ZIF-8). The process, referred to as "nanopore lithography", makes
      use of graphene oxide (GO) nanosheets enclosing ZIF-8 particles as masks or
      templates for the transfer of mesoporous texture to the latter. Upon controlled
      carbonization and activation, nanopores created in the GO envelope serve as
      selective entry points for localized etching of carbonized ZIF-8, so that such
      nanopores are replicated in the MOF-derived carbonaceous structure. The resulting
      porous carbons are dominated by uniform mesopores ~3-4 nm in width and possess
      specific surface areas of ~1300-1400 m2 g-1. Furthermore, we investigate and
      discuss the specific experimental conditions that afford the mesopore-templating
      action of the GO nanosheets. Electrochemical characterization revealed an
      improved capacitance as well as a faster, more reversible charge/discharge
      kinetics for the ZIF-8-derived porous carbons obtained through nanopore
      lithography, relative to those for their counterparts with standard activation
      (no GO templating), thus indicating the potential practical advantage of the
      present approach in capacitive energy storage applications.

PMID- 29215877
TI  - Gas-Phase Acidities and Basicities of Alanines and N-Benzylalanines by the
      Extended Kinetic Method.
AB  - This paper reports an experimental determination of the gas-phase acidities and
      basicities of N-benzylalanines, in both their alpha and beta forms, by means of
      the extended kinetic method (EKM). The experimental gas-phase acidity of beta
      alanine was also determined. Standard ab initio molecular orbital calculations at
      the G3 level were performed for alanines, and at the G3(MP2)//B3LYP level for N
      benzylalanines. There is a very good agreement between the experimental and the
      calculated values. The more branched alpha-amino acids are more acidic and less
      basic than the linear beta-amino acids.

PMID- 29215876
TI  - Deep Learning of Atomically Resolved Scanning Transmission Electron Microscopy
      Images: Chemical Identification and Tracking Local Transformations.
AB  - Recent advances in scanning transmission electron and scanning probe microscopies
      have opened exciting opportunities in probing the materials structural parameters
      and various functional properties in real space with angstrom-level precision.
      This progress has been accompanied by an exponential increase in the size and
      quality of data sets produced by microscopic and spectroscopic experimental
      techniques. These developments necessitate adequate methods for extracting
      relevant physical and chemical information from the large data sets, for which a
      priori information on the structures of various atomic configurations and lattice
      defects is limited or absent. Here we demonstrate an application of deep neural
      networks to extract information from atomically resolved images including
      location of the atomic species and type of defects. We develop a "weakly
      supervised" approach that uses information on the coordinates of all atomic
      species in the image, extracted via a deep neural network, to identify a rich
      variety of defects that are not part of an initial training set. We further apply
      our approach to interpret complex atomic and defect transformation, including
      switching between different coordination of silicon dopants in graphene as a
      function of time, formation of peculiar silicon dimer with mixed 3-fold and 4
      fold coordination, and the motion of molecular "rotor". This deep learning-based
      approach resembles logic of a human operator, but can be scaled leading to
      significant shift in the way of extracting and analyzing information from raw
      experimental data.

PMID- 29215878
TI  - Ultrafast Screening of a Novel, Moderately Hydrophilic Angiotensin-Converting
      Enzyme-Inhibitory Peptide, RYL, from Silkworm Pupa Using an Fe-Doped-Silkworm
      Excrement-Derived Biocarbon: Waste Conversion by Waste.
AB  - A novel, moderately hydrophilic peptide (RYL) with high ACE-inhibitory activity
      was screened ultrafast via a concept of waste conversion using waste. This novel
      peptide was screened from silkworm pupa using an Fe-doped porous biocarbon (FL/Z
      SE) derived from silkworm excrement. FL/Z-SE possessed magnetic properties and
      specific selection for peptides due to Fe's dual functions. The selected RYL,
      which has moderate hydrophilicity (LogP = -0.22), exhibited a comparatively high
      ACE-inhibitory activity (IC50 = 3.31 +/- 0.11 MUM). The inhibitory kinetics and
      docking-simulation results show that, as a competitive ACE inhibitor, RYL formed
      five hydrogen bonds with the ACE residues in the S1 and S2 pockets. In this work,
      both the screening carbon material and the selected ACE-inhibitory peptide were
      derived from agricultural waste (silkworm excrement and pupa), which offers a new
      way of thinking about the development of advanced uses of the silkworm byproducts
      and wastes.

PMID- 29215879
TI  - Computational Kinetic Modeling of the Catalytic Cycle of Glutathione Peroxidase
      Nanomimic: Effect of Nucleophilicity of Thiols on the Catalytic Activity.
AB  - The catalytic cycle of a new derivative of ebselen, 1, was elucidated via three
      steps by the density functional theory and solvent-assisted proton exchange
      procedure involving indirect proton exchange through a hydrogen-bonded transfer
      network. Different behaviors of the aromatic and aliphatic thiols were
      investigated in the reduction of selenoxide (step 2 -> 3) and selenurane (step 3 
      > 1) based on their nucleophilicity. The reduction of selenoxide in the presence
      of thiophenol (DeltaG? = 15.9 kcal.mol-1) is faster than that of methanethiol
      (DeltaG? = 29.3 kcal.mol-1), and methanethiol makes the reduction of selenoxide
      unspontaneous and kinetically unfavorable (DeltaG = 2.8 kcal.mol-1). The
      nucleophilic attack may be enhanced by using the thiophenol backbone at the
      selenium center to lower the energy barrier of the selenoxide reduction (DeltaG?
      = 15.9 kcal.mol-1). On the basis of the turnover frequency calculations, during
      the catalytic cycle, the rate of the reaction was analyzed and discussed. Low
      values of the electron density and Laplacian at the transition states are the
      evidence of the covalent O-H and O-O bonds rupture in the presence of
      methanethiol and thiophenol. The nature of the critical bond points was
      characterized, using the quantum theory of atoms in molecules, based on the
      electron location function and localized orbital locator values. Finally, the
      charge transfer process at the rate-determining step was investigated based on
      the natural bond orbital analysis.

PMID- 29215881
TI  - Preparation of Quaternary Centers via Nickel-Catalyzed Suzuki-Miyaura Cross
      Coupling of Tertiary Sulfones.
AB  - We describe the development of a nickel-catalyzed Suzuki-Miyaura cross-coupling
      of tertiary benzylic and allylic sulfones with arylboroxines. A variety of
      tertiary sulfones, which can easily be prepared via a deprotonation-alkylation
      route, were reacted to afford symmetric and unsymmetric quaternary products in
      good yields. We highlight the use of either BrettPhos or Doyle's phosphines as
      effective ligands for these challenging desulfonative coupling reactions. The
      utility of this methodology was demonstrated in the concise synthesis of a
      vitamin D receptor modulator analogue.

PMID- 29215880
TI  - Neuroprotective Effects of 1,2-Diarylpropane Type Phenylpropanoid Enantiomers
      from Red Raspberry against H2O2-Induced Oxidative Stress in Human Neuroblastoma
      SH-SY5Y Cells.
AB  - Red raspberry (Rubus idaeus L.) is an edible fruit-producing species belonging to
      the Rosaceae family. In our search for the health-promoting constituents from
      this fruit, four pairs of enantiomeric phenylpropanoids (1a/1b-4a/4b), including
      three new compounds (1a and 2a/2b), were isolated from red raspberry. Their
      structures were elucidated by a combination of the extensive NMR spectroscopic
      data analyses, high-resolution electrospray ionization mass spectrometry and
      comparison between the experimental measurements of electronic circular dichroism
      (ECD) and calculated ECD spectra by time-dependent density functional theory
      (TDDFT). In addition, their neuroprotective effects against H2O2-induced
      oxidative stress in human neuroblastoma SH-SY5Y cells were investigated, and the
      results showed enantioselectivity, in which that 3a exhibited noticeable
      neuroprotective activity, while its enatiomer 3b exhibited no obvious protective
      effect. Further study demonstrated that 3a could selectively inhibit the
      apoptosis induction and reactive oxygen species (ROS) accumulation by enhancing
      the activity of catalase (CAT) in H2O2-treated human neuroblastoma SH-SY5Y cells.
      These findings shed much light on a better understanding of the neuroprotective
      effects of these enantiomers and provide new insights into developing better
      treatment of neurodegenerative diseases in the future.

PMID- 29215882
TI  - Theoretical Models for Quantitative Description of the Acid-Base Equilibria of
      the 5,6-Substituted Uracils.
AB  - The acidities of 18 5,6-substituted uracils have been numerically estimated as
      pKa values in terms of three theoretical models. The first scheme includes the
      calculation of the gas-phase acidity of uracil with the G3MP2B3 method and taking
      into account the solvent effect using the polarizable continuum approximation
      PCM(SMD)-TPSS/aug-cc-pVTZ. The second model is one step and implies calculation
      of the free Gibbs energies of the hydrate complex of uracil (and its anion) with
      5 water molecules by the TPSS/aug-cc-pVTZ method. This model accounts for the
      solvent effect corresponding to both specific and nonspecific solvation. The
      third scheme required high time and computational resources and includes the
      strong features of the two previous schemes. Here, the theoretical estimation of
      pKa is performed by the CBS-QB3 composite method. As in the second approach, both
      specific (as pentahydrate) and nonspecific solvent effects are determined. We
      have analyzed the advantages and model restrictions of the considered schemes for
      the pKa calculations. All models have systematic errors, which have been
      corrected with the linear empirical regression relations. In the presented model,
      the absolute mean deviations of the pKa values of uracils dissociating via the N1
      H bonds diminish to 0.25, 0.28, and 0.23 pKa units (respectively, for I, II, and
      III models), which corresponds to ~0.3 kcal/mol on the energy scale. The
      applicability of our computational schemes to uracils dissociating via N3-H, O-H
      (orotic acids) and C-H bonds is discussed.

PMID- 29215883
TI  - Conformational Map of Phenolic Acids.
AB  - The benefits of vaporization by laser ablation and the high resolution and
      sensitivity attained by the chirped pulse Fourier transform microwave
      spectroscopy CP-FTMW have provided the first conformational map of the simplest
      phenolic acids of trans-cinnamic and p-coumaric. Two conformers of trans-cinnamic
      acid and four conformers of trans-p-coumaric acid have been characterized under
      the isolation conditions of a supersonic expansion. The spectroscopic constants
      derived from the analysis of the rotational spectra compared with those predicted
      theoretically provide an unmatched means to achieve an unambiguous identification
      of the observed species.

PMID- 29215884
TI  - Quantum Spin Liquid from a Three-Dimensional Copper-Oxalate Framework.
AB  - The quantum spin liquid (QSL) state is of great interest in relation to quantum
      computation and superconductivity and the search for new QSL materials is a
      current challenge in chemistry. Existing inorganic and molecular QSL compounds
      have two-dimensional structures, with spins arranged on triangular and kagome
      lattices, whereas three-dimensional structures with QSL characteristics are rare.
      In the copper-oxalate framework compound [(C2H5)3NH]2Cu2(C2O4)3, Cu(II) is
      coordinated with three bisbidentate oxalate bridges to form a three-dimensional
      (10,3) lattice and this produces a strong antiferromagnetic interaction between
      Cu2+ (S = 1/2) atoms (theta = -180 K). No long-range ordering (LRO) was observed
      in either magnetic susceptibility or specific heat measurements down to 2 K.
      Absence of LRO was further confirmed by MUSR measurements down to 60 mK,
      indicating that it is a gapless QSL with f > 3000. Due to Jahn-Teller distortion
      and partial dimerization, the effective dimensionality of the magnetic lattice is
      reduced. This compound nevertheless highlights the great potential for obtaining
      QSLs of varying dimensionality from metal-organic frameworks.

PMID- 29215885
TI  - Dynamic Ligand Exchange as a Mechanistic Probe in Pd-Catalyzed Enantioselective C
      H Functionalization Reactions Using Monoprotected Amino Acid Ligands.
AB  - A new tool for probing enantioselective reaction mechanisms is introduced.
      Monitoring the temporal change in product enantiomeric excess after addition of
      the opposite enantiomer of the ligand during the reaction provides a means of
      probing dynamic ligand exchange in enantioselective C-H iodination catalyzed by
      Pd with monoprotected amino acid ligands (MPAAs). This work has general potential
      to provide insights about the dynamics of catalyst and ligand molecularity and
      exchange.

PMID- 29215886
TI  - Bibenzyl-Based Meroterpenoid Enantiomers from the Chinese Liverwort Radula
      sumatrana.
AB  - Six new pairs of bibenzyl-based meroterpenoid enantiomers, (+/-)-rasumatranin A-D
      (1-4) and (+/-)-radulanin M and N (5 and 6), and six known compounds were
      isolated from the adnascent Chinese liverwort, Radula sumatrana. Their structures
      were elucidated based on spectroscopic data and chiral phase HPLC-ECD analyses.
      The structures of 1 and 7 were also confirmed by single-crystal X-ray diffraction
      analysis. Cytotoxicity tests of the isolated compounds showed that 6-hydroxy-3
      methyl-8-phenylethylbenzo[b]oxepin-5-one (8) showed activity against the human
      cancer cell lines MCF-7, PC-3, and SMMC-7721, with IC50 values of 3.86, 6.60, and
      3.58 MUM, respectively, and induced MCF-7 cell death through a mitochondria
      mediated apoptosis pathway.

PMID- 29215887
TI  - Unique Hydrogen Bonds in Membrane Protein Monitored by Whole Mid-IR ATR
      Spectroscopy in Aqueous Solution.
AB  - Protein function is coupled to its structural changes, for which stimulus-induced
      difference Fourier-transform infrared (FTIR) spectroscopy is a powerful method.
      By optimizing the attenuated total reflection (ATR)-FTIR analysis on sodium
      pumping rhodopsin KR2 in aqueous solution, we first measured the accurate
      difference spectra upon sodium binding in the whole IR region (4000-1000 cm-1).
      The new spectral window allows the analysis of not only the fingerprint region
      (1800-1000 cm-1) but also the hydrogen-bonding donor region (4000-1800 cm-1),
      revealing an unusually strong hydrogen bond of Tyr located in the sodium binding
      site of KR2. Progress in ATR-FTIR difference spectroscopy provides an approach to
      investigating stimulus-induced structural changes of membrane proteins under
      physiological aqueous conditions.

PMID- 29215888
TI  - Flow Cytometric Analysis To Evaluate Morphological Changes in Giant Liposomes As
      Observed in Electrofusion Experiments.
AB  - Liposome fusion is a way of supplying additional components for in-liposome
      biochemical reactions. Electrofusion is a method that does not require the
      addition of fusogens, which often alter the liposome dispersion, and is therefore
      useful for repetitive liposome fusion. However, the details of electrofusion have
      not been elucidated because of the limitations surrounding observing liposomes
      using a microscope. Therefore, we introduced fluorescent markers and high
      throughput flow cytometry to analyze the morphological changes that occur in
      liposome electrofusion. (i) The content mixing was evaluated by a calcein-Co2+
      EDTA system, in which green fluorescence from dequenched free calcein is detected
      when the quenched calcein-Co2+ complex and EDTA are mixed together. (ii) Liposome
      destruction was evaluated from the decrease in the total membrane volume of giant
      liposomes. (iii) Liposome fission was evaluated from the increase in the number
      of giant liposomes. By applying the flow cytometric analysis, we investigated the
      effect of three parameters (DC pulse, AC field, and lipid composition) on
      liposome electrofusion. The larger numbers or higher voltages of DC pulses
      induced liposome fusion and destruction with higher probability. The longer
      application time of the AC field induced liposome fusion, fission, and
      destruction with higher probability. Higher content of negatively charged POPG
      (>=19%) strongly inhibited liposome electrofusion.

PMID- 29215889
TI  - Correction to "Tailoring the Electrochemical Properties of Carbon Nanotube
      Modified Indium Tin Oxide via in Situ Grafting of Aryl Diazonium".

PMID- 29215890
TI  - Control of Gallium Oxide Growth on Liquid Metal Eutectic Gallium/Indium
      Nanoparticles via Thiolation.
AB  - Eutectic gallium-indium alloy (EGaIn, a room-temperature liquid metal)
      nanoparticles are of interest for their unique potential uses in self-healing and
      flexible electronic devices. One reason for their interest is due to a
      passivating oxide skin that develops spontaneously on exposure to ambient
      atmosphere which resists deformation and rupture of the resultant liquid
      particles. It is then of interest to develop methods for control of this oxide
      growth process. It is hypothesized here that functionalization of EGaIn
      nanoparticles with thiolated molecules could moderate oxide growth based on
      insights from the Cabrera-Mott oxidation model. To test this, the oxidation
      dynamics of several thiolated nanoparticle systems were tracked over time with X
      ray photoelectron spectroscopy. These results demonstrate the ability to suppress
      gallium oxide growth by up to 30%. The oxide progressively matures over a 28 day
      period, terminating in different final thicknesses as a function of thiol
      selection. These results indicate not only that thiols moderate gallium oxide
      growth via competition with oxygen for surface sites but also that different
      thiols alter the thermodynamics of oxide growth through modification of the EGaIn
      work function.

PMID- 29215891
TI  - Combining Visible-Light-Photoredox and Lewis Acid Catalysis for the Synthesis of
      Indolizino[1,2-b]quinolin-9(11H)-ones and Irinotecan Precursor.
AB  - One-step construction of substituted indolizino[1,2-b]quinolin-9(11H)-ones was
      achieved by combining visible-light-photoredox and Lewis acid catalysis for an
      intramolecular Povarov cycloaddition reaction under mild conditions. In this
      catalytic process, the visible-light-promoted dehydrogenation protocol of
      tetrahydroquinolines constitutes the key procedure. Moreover, this method can be
      applied to the formal synthesis of the precursor of irinotecan, which exhibited
      good anticancer activities.

PMID- 29215892
TI  - Molecular Dynamics Simulation of the pH-Induced Structural Transitions in
      CTAB/NaSal Solution.
AB  - We performed molecular dynamics simulations to study the pH-induced structural
      transitions for aqueous mixtures of a cationic surfactant (cetyltrimethylammonium
      bromide, CTAB) and a hydrotrope (sodium salicylate, NaSal). We obtained rigid
      cylindrical, spherical, and flexible cylindrical micelles at pH 7, 2, and 0,
      respectively, which agrees well with the experimental results of Umeasiegbu et
      al. (Langmuir 2016, 32, 655). By analyzing the different micellar structural
      properties, including distribution and molecular orientation of CTA+ and Sal-
      inside the micelle, we found that the binding form of the protonated salicylate
      molecules with CTA+ is different from that of Sal- ions. Because of the
      protonation of salicylate molecules with reduction in pH, their hydrogen bonding
      interactions with water molecules strengthened and the electrostatic interactions
      with CTA+ headgroups weakened. Thus, the repulsion of the CTA+ headgroups led to
      the breakage of the cylindrical micelle into spherical ones. At pH 0, the H-bond
      strengthened cation-pi interactions between salicylate and CTA+ were verified. We
      concluded that the penetration of salicylate molecules inside the micelle and the
      strong association of Cl- ions on the micellar surface play a key role in the
      formation of a flexible cylindrical micelle. This work provides an atomic-level
      insight into the mechanism of pH-induced shape transitions in the CTAB/NaSal
      systems, which is expected to be helpful to understand the aggregate behavior of
      cationic surfactant-hydrotrope solution.

PMID- 29215893
TI  - Bright Electroluminescence from Single Graphene Nanoribbon Junctions.
AB  - Thanks to their highly tunable band gaps, graphene nanoribbons (GNRs) with
      atomically precise edges are emerging as mechanically and chemically robust
      candidates for nanoscale light emitting devices of modulable emission color.
      While their optical properties have been addressed theoretically in depth, only
      few experimental studies exist, limited to ensemble measurements and without any
      attempt to integrate them in an electronic-like circuit. Here we report on the
      electroluminescence of individual GNRs suspended between the tip of a scanning
      tunneling microscope (STM) and a Au(111) substrate, constituting thus a realistic
      optoelectronic circuit. Emission spectra of such GNR junctions reveal a bright
      and narrow band emission of red light, whose energy can be tuned with the bias
      voltage applied to the junction, but always lying below the gap of infinite GNRs.
      Comparison with ab initio calculations indicates that the emission involves
      electronic states localized at the GNR termini. Our results shed light on
      unpredicted optical transitions in GNRs and provide a promising route for the
      realization of bright, robust, and controllable graphene-based light-emitting
      devices.

PMID- 29215894
TI  - Selective Low-Energy Carbon Dioxide Adsorption Using Monodisperse Nitrogen-Rich
      Hollow Carbon Submicron Spheres.
AB  - Monodisperse, nitrogen-doped hollow carbon spheres of submicron size were
      synthesized using hexamethoxymethylmelamine as both a carbon and nitrogen source
      in a short (1 h) microwave-assisted synthesis. After carbonization at 550 
      degrees C, porous carbon spheres with a remarkably high nitrogen content of 37.1%
      were obtained, which consisting mainly of highly basic pyridinic moieties. The
      synthesized hollow spheres exhibited high selectivity for carbon dioxide (CO2)
      over nitrogen and oxygen gases, with a capture capacity up to 1.56 mmol CO2 g-1.
      The low adsorption enthalpy of the synthesized hollow carbon spheres permits good
      adsorbent regeneration. Evaluation of the feasibility of scaling up shows their
      potential for large-scale applications.

PMID- 29215895
TI  - Role of Grounded Liquid Collectors in Precise Patterning of Electrospun Nanofiber
      Mats.
AB  - Liquid collectors are applicable as ground collectors in electrospinning, which
      fabricates complex nanofiber architectures. However, the influence of the
      electrical properties of liquid collectors on the controlled deposition of
      electrospun nanofiber mats has received little attention. Here, we prepare two
      types of liquid collectors (electrolyte solutions and dielectric liquids) and
      newly scrutinize their roles in the patterning of electrospun nanofiber mats in
      experiments and in numerical simulations. By simulating the concentrations of the
      electric fields around the liquid collectors, we indirectly evaluated the
      patternability of the collectors. The patternability trends were verified by the
      patterning of nanofiber mats on line-array-shaped liquid collectors fabricated by
      electrospinning. The deposition accuracy of the electrolyte solution collector
      was very high, equivalent to that of a conventional metal collector even at low
      salt concentrations (e.g., 0.01 M KCl). However, the nanofiber mats fabricated by
      electrospinning with the dielectric liquid collector showed retarded
      patternability.

PMID- 29215896
TI  - High-Speed but Not Magic: Microwave-Assisted Synthesis of Ultra-Small Silver
      Nanoparticles.
AB  - Reaction procedures have been improved to achieve higher yields and shorter
      reaction times: one possibility is the usage of microwave reactors. In the
      literature, this is under discussion, for example, nonthermal effects resulting
      from the microwave radiation are claimed. Especially for the synthesis of
      nanomaterials, it is of crucial importance to be aware of influences on the
      reaction pathway. Therefore, we compare the syntheses of ultra-small silver
      nanoparticles via conventional and microwave heating. We employed a versatile one
      pot polyol synthesis of poly(acrylic acid)-stabilized silver nanoparticles, which
      display superior catalytic properties. No microwave-specific effects in terms of
      particle size distribution characteristics, as derived by small-angle X-ray
      scattering and dynamic light scattering, are revealed. Because of the
      characteristics of a closed system, microwave reactors give access to elevated
      temperatures and pressures. Therefore, the speed of particle formation can be
      increased by a factor of 30 when the reaction temperature is increased from 200
      to 250  degrees C. The particle growth process follows a cluster coalescence
      mechanism. A postsynthetic incubation step at 250  degrees C induces a further
      growth of the particles while the size distribution broadens. Thus, utilization
      of microwave reactors enables an enormous decrease of the reaction time as well
      as the opportunity of tuning the particle size. Possibly, decomposition of the
      stabilizing ligand at elevated temperatures results in reduced yields. A
      compromise between short reaction times and high yields can be found at a
      temperature of 250  degrees C and a corresponding reaction time of 30 s.

PMID- 29215897
TI  - Counterion-Induced Control of the Colloidal State of Polyamic Acid Nanoparticles
      for Electrophoretic Deposition.
AB  - Optimizing the colloidal state of polyamic acid (PAA) nanoparticles is essential
      for achieving a uniform and high-performance polyimide coating by electrophoretic
      deposition (EPD) on metal substrates of various shapes. In this paper, we report
      two important roles of the counterions in the formation of PAA colloids for EPD,
      which, to date, have not been recognized. First, when tertiary alkyl amines are
      used to neutralize PAA, the polarity of neutralizing counterions determines the
      size and stability of the PAA colloidal particles. The polarity can be finely
      tuned by using two different tertiary alkyl amines containing polar and nonpolar
      groups and adjusting the molar ratio. Depending on the polar/nonpolar ratio,
      various states of PAA colloids were obtained, including dissolved state, stable
      colloid, and aggregates. Second, we observed that the confined counterions inside
      PAA nanoparticles can act as an imidization catalyst during the thermal annealing
      process. It is revealed that some fraction of the counterion species, mostly
      having nonpolar groups, is not drawn toward the counter electrode and remains
      inside the PAA nanoparticles during the EPD process. Optimizing the polarity
      eventually allowed us to form uniform EPD coatings with high dielectric
      strengths.

PMID- 29215898
TI  - Significantly High Thermal Rectification in an Asymmetric Polymer Molecule Driven
      by Diffusive versus Ballistic Transport.
AB  - Tapered bottlebrush polymers have novel nanoscale polymer architecture. Using
      nonequilibrium molecular dynamics simulations, we showed that these polymers have
      the unique ability to generate thermal rectification in a single polymer molecule
      and offer an exceptional platform for unveiling different heat conduction
      regimes. In sharp contrast to all other reported asymmetric nanostructures, we
      observed that the heat current from the wide end to the narrow end (the forward
      direction) in tapered bottlebrush polymers is smaller than that in the opposite
      direction (the backward direction). We found that a more disordered to less
      disordered structural transition within tapered bottlebrush polymers is essential
      for generating nonlinearity in heat conduction for thermal rectification.
      Moreover, the thermal rectification ratio increased with device length, reaching
      as high as ~70% with a device length of 28.5 nm. This large thermal rectification
      with strong length dependence uncovered an unprecedented phenomenon-diffusive
      thermal transport in the forward direction and ballistic thermal transport in the
      backward direction. This is the first observation of radically different
      transport mechanisms when heat flow direction changes in the same system. The
      fundamentally new knowledge gained from this study can guide exciting research
      into nanoscale organic thermal diodes.

PMID- 29215899
TI  - Tool use in left-brain-damaged patients: Difficulties in reasoning but not in
      estimating the physical properties of objects.
AB  - OBJECTIVE: The purpose of this study was to deepen our understanding of the
      cognitive bases of human tool use based on the technical reasoning hypothesis
      (i.e., the reasoning-based approach). This approach assumes that tool use is
      supported by the ability to reason about an object's physical properties (e.g.,
      length, weight, strength, etc.) to perform mechanical actions (e.g., lever). In
      this framework, an important issue is to understand whether left-brain-damaged
      (LBD) individuals with tool-use deficits are still able to estimate the physical
      object's properties necessary to use the tool. METHOD: Eleven LBD patients and 12
      control participants performed 3 original experimental tasks: Use-Length (visual
      evaluation of the length of a stick to bring down a target), Visual-Length (to
      visually compare objects of different lengths) and Addition-Length (to visually
      compare added lengths). Participants were also tested on conventional tasks:
      Familiar Tool Use and Mechanical Problem-Solving (novel tools). RESULTS: LBD
      patients had more difficulties than controls on both conventional tasks. No
      significant differences were observed for the 3 experimental tasks. CONCLUSION:
      These results extend the reasoning-based approach, stressing that it might not be
      the representation of length that is impaired in LBD patients, but rather the
      ability to generate mechanical actions based on physical object properties.
      (PsycINFO Database Record

PMID- 29215900
TI  - APOE e4-genotype and lifestyle interaction on cognitive performance: Results of
      the LIFE-Adult-study.
AB  - OBJECTIVE: Previous studies have shown that the e4-allele of the APOE gene is
      associated with a higher risk of developing dementia. Our study investigated
      whether well-known associations between lifestyle factors and cognitive
      functioning may be stronger in individuals who carry the dementia risk variant of
      the APOE gene and whether this association is amplified with older age. METHOD:
      Data analysis comprised 7,526 participants (aged 40- to 79-years-old) from the
      population-based LIFE-Adult-study. The effect of the APOE e4-allele on the
      association between lifestyle factors (smoking, physical activity, being
      overweight, occupational attainment) and cognitive performance (trail making test
      [TMT] B, verbal fluency test [VFT]) was analyzed via multivariate generalized
      linear modeling adjusted for APOE e2-allele, age, gender, education, stroke, and
      heart attack. RESULTS: Smoking, less physical activity, and lower occupational
      attainment was associated with a poorer performance in the TMT B and VFT. Neither
      the APOE e4-allele nor interactions with the APOE e4-allele were significantly
      associated with cognitive performance. The association between physical activity
      and occupational attainment on performance in the TMT B were stronger in older
      age, but the APOE gene did not modify those associations. CONCLUSIONS: Our
      findings suggest that the dementia risk variant of the APOE gene does not alter
      the association between lifestyle factors and cognitive performance in the
      general population aged 40- to 79-years-old. However, as lifestyle factors impact
      cognitive aging, research efforts should focus on establishing effective
      interventions promoting healthy lifestyle behaviors to counteract adverse
      cognitive aging processes. (PsycINFO Database Record

PMID- 29215901
TI  - Introduction of the DSM-5 levels of Personality Functioning Questionnaire.
AB  - With the introduction in the Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition (DSM-5) of a hybrid system of personality disorder
      assessment, the ability to assess patients' traits, as well as their level of
      personality functioning, has become increasingly important. To assess this
      criterion, the DSM-5 Levels of Personality Functioning Questionnaire (DLOPFQ) was
      developed. The DLOPFQ assesses individuals' self-impairments and other
      impairments in several domains (self-direction, identity, empathy, and intimacy)
      and across 2 contexts (work/school and relationships). A sample of 140
      psychiatric and medical outpatients was administered the DLOPFQ and several other
      measures to assess its reliability and construct, incremental, and discriminant
      validity. The internal consistency and convergence with validation measures
      yielded generally meaningful and expected results. Several DLOPFQ scales and
      subscales were significantly correlated with measures of DSM-5 trait domains and
      levels of personality functioning. DLOPFQ scales also correlated with self
      reported ratings of overdependence, detachment, healthy dependency, and overall
      mental health and well-being. The DLOPFQ also predicted interpersonal and general
      functioning beyond DSM-5 trait domains. These results support the reliability and
      validity of the DLOPFQ, which appears to be suitable for clinical use and
      warrants ongoing study. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29215902
TI  - Words matter: Implementing the electronically activated recorder in schizotypy.
AB  - In schizophrenia-spectrum populations, analyzing the words people use has offered
      promise for unlocking information about affective states and social behaviors.
      The electronically activated recorder (EAR) is an application-based program that
      is combined with widely used smartphone technology to capture a person's real
      world interactions via audio recordings. It improves on the ecological validity
      of current methodologies by providing objective and naturalistic samples of
      behavior. This study is the first to implement the EAR in people endorsing
      elevated traits of schizophrenia-spectrum personality disorders (i.e.,
      schizotypy), and we expected the EAR to (a) differentiate high and low schizotypy
      groups on affective disturbances and social engagement and (b) show that high
      schizotypy status moderates links between affect and social behavior using a
      multimethod approach. Lexical analysis of EAR recordings revealed greater
      negative affect and decreased social engagement in those high in schizotypy. When
      assessing specific traits, EAR and ecological momentary assessment (EMA)
      converged to show that positive schizotypy predicted negative affect. Finally,
      high schizotypy status moderated links between negative affect and social
      engagement when the EAR was combined with EMA. Adherence did not influence
      results, as both groups wore the EAR more than 90% of their waking hours.
      Findings supported using the EAR to assess real-world expressions of personality
      and functioning in schizotypy. Evidence also showed that the EAR can be used
      alongside EMA to provide a mixed-method, real-world assessment that is high in
      ecological validity and offers a window into the daily lives of those with
      elevated traits of schizophrenia-spectrum personality disorders. (PsycINFO
      Database Record

PMID- 29215903
TI  - Clinician ratings of vulnerable and grandiose narcissistic features: Implications
      for an expanded narcissistic personality disorder diagnosis.
AB  - Conceptualizations of narcissistic personality disorder (NPD) in the Diagnostic
      and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric
      Association, 2013) have been criticized for focusing too exclusively on grandiose
      narcissistic traits (e.g., exploitativeness and entitlement) and failing to
      capture vulnerable narcissistic features (e.g., feelings of inadequacy). We
      extended prior grandiose and vulnerable narcissism research by examining the
      degree to which clinician ratings of traits related to grandiosity overlapped
      with traits related to vulnerability in a large sample of adult outpatients (N =
      2,149). We also examined relations with other psychopathology and psychosocial
      impairment for both (a) narcissistic trait configurations including both
      vulnerable and grandiose features and (b) configurations focusing on grandiose
      narcissistic traits. Structural results indicated that some personality features
      related to vulnerability (e.g., perfectionism and inadequacy) were unrelated to
      ratings of grandiose narcissistic personality features. Additionally, our results
      suggest that emphasizing vulnerable features within narcissism trait
      configurations may increase NPD's overlap with other disorders (e.g., borderline
      personality disorder and social anxiety) and does not appear to discriminate
      pathological narcissism from antisocial personality disorder, a disorder with
      which NPD is highly comorbid. Finally, scores on configurations defined only by
      grandiose narcissistic traits related positively to all psychosocial impairment
      indicators, although configurations also including vulnerable features generally
      showed stronger relations with psychosocial impairment. The implications of these
      findings in regard to future conceptualizations of NPD are discussed. (PsycINFO
      Database Record

PMID- 29215904
TI  - Practice procedures in models of primary care collaboration for children with
      ADHD.
AB  - INTRODUCTION: With nationwide movement toward an integrated medical home,
      evidence to support, compare, and specify effective models for collaboration
      between primary care and behavioral health professionals is essential. This study
      compared 2 models of primary care with behavioral health integration on American
      Academy of Pediatrics guideline adherence for attention-deficit/hyperactivity
      disorder (ADHD) assessment and treatment. METHOD: We conducted a retrospective
      chart review of a random sample of children aged 6-13 years, seen for ADHD
      services in 2 primary care offices, 1 fully integrated model and 1 co-located
      service only model, comparing ADHD assessment and treatment practices. We used
      chi-square analyses and logistic regression modeling to determine differences by
      type of health care model. RESULTS: Among children with ADHD (n = 149), the
      integrated care model demonstrated higher rates of guideline adherence, more
      direct contact with schools, and more frequent behavioral observation during
      clinical encounters. Families in the integrated practice received more caregiver
      education on ADHD, behavioral management training, and school advocacy, however,
      these associations did not remain after accounting for variance associated with
      onsite engagement with a psychologist. Practices were equivalent on use of
      medication and psychiatric consultation, although, more families in the
      integrated practice engaged with a psychologist and attended more frequent
      medication follow-up appointments than those in the co-located practice.
      DISCUSSION: This study is among the first to compare different levels of
      collaborative care on practice procedures. Understanding how we can best
      integrate between behavioral health and primary care services will optimize
      outcomes for children and families. (PsycINFO Database Record

PMID- 29215905
TI  - Patient-perceived family stigma of Type 2 diabetes and its consequences.
AB  - INTRODUCTION: Adults with type two diabetes (T2D) report being monitored and
      judged by family members, contributing to feelings of guilt/shame, and attempts
      to conceal one's diabetes status or self-care efforts. However, studies have not
      yet quantitatively examined T2D stigma from family members. Our objective was to
      assess the frequency of T2D family stigma and its association with helpful and
      harmful diabetes-specific family behaviors and psychological and behavioral
      consequences of stigma. METHOD: A sample of predominantly African-American adults
      with T2D and low income completed items written for this study to assess T2D
      family stigma and consequences of stigma. We explored frequencies and bivariate
      correlations between these constructs and diabetes-specific family behaviors
      (measured with the Diabetes Family Behavior Checklist-II). RESULTS: Participants
      (N = 53) were 57.3 +/- 8.7 years old, 70% African American, 96% had annual
      incomes <$20K, and average HbA1C was 8.0 +/- 2.2%. More than half (57%) reported
      at least 1 experience of family stigma (1.26 +/- 1.8 of 9 queried, alpha = .84),
      and 28% reported at least 1 consequence (0.6 +/- 1.3 of 5 queried, alpha = .87).
      Reporting more family stigma was associated with more consequences (rho = .52, p
      < .001) but not with helpful or harmful family behaviors. DISCUSSION:
      Perceptions/experiences of T2D-related family stigma were common in our sample
      and associated with consequences of stigma including concealment and resentment
      of self-care, which may affect clinical outcomes. (PsycINFO Database Record

PMID- 29215906
TI  - Parental perspectives of screening for adverse childhood experiences in pediatric
      primary care.
AB  - INTRODUCTION: Pediatricians recognize a need to mitigate the negative impact that
      adverse childhood experiences (ACEs) can have on health and development. However,
      ACEs screening and interventions in primary care pediatrics may be inhibited by
      concerns about parental perceptions. We assessed parent perspectives of screening
      for ACEs in the pediatric primary care setting, to understand their views on the
      potential impact of their ACEs on their parenting and to identify opportunities
      for pediatric anticipatory guidance. METHOD: We used purposive sampling to
      recruit parents of children <6 years receiving care at an urban, pediatric
      clinic. Semistructured questions guided 1:1 interviews that were later coded by
      multiple researchers to verify reliability. A thematic framework approach guided
      analysis and identified main themes and subthemes. RESULTS: We reached thematic
      saturation after 15 parent interviews, which consistently revealed 3 interrelated
      themes. First, parents strongly supported ACEs screening as a bridge to needed
      services, and they recommended using a trauma-sensitive, person-centered approach
      in pediatric practices. Second, parents understood the intergenerational impact
      of ACEs and expressed a desire to break the cycle of adversity. Finally, parents
      saw their child's pediatrician as a potential change-agent who could provide
      support to meet their parenting goals. DISCUSSION: Parents want to discuss their
      ACEs and receive help and guidance from pediatricians. Furthermore, they perceive
      their child's pediatrician as having an important role to play in meeting their
      parenting goals. It is important to ensure that pediatricians have the training,
      skills and familiarity with available resources to meet parental expectations.
      (PsycINFO Database Record

PMID- 29215907
TI  - Chemotherapy and cognitive impairment: An animal model approach.
AB  - A substantial number of cancer survivors who undergo chemotherapy report
      cognitive disturbances that severely limit daily function (chemobrain). Despite
      supportive neuropsychological evidence, there is controversy over whether
      cognitive impairment is caused by the chemotherapy or is the result of
      potentially confounding factors that include the disease itself, age, and
      psychological stress. Our research program, conducted on rodents, has confirmed
      that a range of cognitive processes, mediated in particular by hippocampal and
      prefrontal brain regions, are affected by anticancer drugs in combination with
      tumor development and that many of the effects are long lasting. This work has
      also provided evidence of protective factors (cognitive reserve, physical
      exercise, environmental enrichment) and the potential of pharmacological
      treatment (donepezil) interventions in reducing these effects. (PsycINFO Database
      Record

PMID- 29215908
TI  - Chronometrage et perception temporelle.
AB  - This article provides an overview of some contemporary research avenues in the
      field of timing and time perception. After a brief description of different
      categories of temporal experiences, the article describes how research on
      psychological time falls within a psychophysical perspective. Next, some factors
      changing sensitivity to time or perceived duration are reported. Four main
      sources affecting this sensitivity are identified : the modality in which the
      intervals to be estimated are marked, the length of the markers, the number of
      intervals presented, and whether people are counting explicitly or not when
      estimating time. When emphasis is placed on the perceived duration of intervals,
      3 important factors of influence are retained: attention, the space between
      markers and emotion and its expression. The biological bases required for
      processing temporal information are then briefly reviewed, and the article ends
      with the description of perturbations of the relation to time in some pathologies
      (schizophrenia, Parkinson's disease and depression). (PsycINFO Database Record

PMID- 29215910
TI  - Your job is messing with mine! The impact of mobile device use for work during
      family time on the spouse's work life.
AB  - The use of mobile technology for work purposes during family time has been found
      to affect employees' work and family lives. Using a matched sample of 344 job
      incumbents and their spouses, we examined the role of mobile device (MD) use for
      work during family time in the job incumbent-spouse relationship and how this MD
      use crosses over to affect the spouse's work life. Integrating the work-home
      resources model with family systems theory, we found that as job incumbents
      engage in MD use for work during family time, work-to-family conflict increases,
      as does the combined experience of relationship tension between job incumbents
      and spouses. This tension serves as a crossover mechanism, which then contributes
      to spouses' experience of family-to-work conflict and, subsequently, family
      spills over to work outcomes for the spouse in the form of reduced job
      satisfaction and performance. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29215909
TI  - Caring for the Elderly at Work and Home: Can a Randomized Organizational
      Intervention Improve Psychological Health?
AB  - Although job stress models suggest that changing the work social environment to
      increase job resources improves psychological health, many intervention studies
      have weak designs and overlook influences of family caregiving demands. We tested
      the effects of an organizational intervention designed to increase supervisor
      social support for work and nonwork roles, and job control in a results-oriented
      work environment on the stress and psychological distress of health care
      employees who care for the elderly, while simultaneously considering their own
      family caregiving responsibilities. Using a group-randomized organizational field
      trial with an intent-to-treat design, 420 caregivers in 15 intervention extended
      care nursing facilities were compared with 511 caregivers in 15 control
      facilities at 4 measurement times: preintervention and 6, 12, and 18 months.
      There were no main intervention effects showing improvements in stress and
      psychological distress when comparing intervention with control sites. Moderation
      analyses indicate that the intervention was more effective in reducing stress and
      psychological distress for caregivers who were also caring for other family
      members off the job (those with elders and those "sandwiched" with both child and
      elder caregiving responsibilities) compared with employees without caregiving
      demands. These findings extend previous studies by showing that the effect of
      organizational interventions designed to increase job resources to improve
      psychological health varies according to differences in nonwork caregiving
      demands. This research suggests that caregivers, especially those with "double
      duty" elder caregiving at home and work and "triple-duty" responsibilities,
      including child care, may benefit from interventions designed to increase work
      nonwork social support and job control. (PsycINFO Database Record

PMID- 29215911
TI  - Weird Animals, Sex, and Genome Evolution.
AB  - Making my career in Australia exposed me to the tyranny of distance, but it gave
      me opportunities to study our unique native fauna. Distantly related animal
      species present genetic variation that we can use to explore the most fundamental
      biological structures and processes. I have compared chromosomes and genomes of
      kangaroos and platypus, tiger snakes and emus, devils (Tasmanian) and dragons
      (lizards). I particularly love the challenges posed by sex chromosomes, which,
      apart from determining sex, provide stunning examples of epigenetic control and
      break all the evolutionary rules that we currently understand. Here I describe
      some of those amazing animals and the insights on genome structure, function, and
      evolution they have afforded us. I also describe my sometimes-random walk in
      science and the factors and people who influenced my direction. Being a woman in
      science is still not easy, and I hope others will find encouragement and empathy
      in my story.

PMID- 29215912
TI  - An Australian Biobank Certification Scheme: A Study of Economic Costs to
      Participating Biobanks.
AB  - Biobanks face increasing demands for research materials of consistent quality,
      which can be used in collaborative studies. Several countries and some
      international agencies have made formal efforts to standardize biobank operations
      and outputs. These include the establishment of best practice guidelines for
      collection management, and certification programs. Such guidelines and programs
      increase biobanks' opportunities for participation in high impact research and
      funding. However, they also impose economic and time costs, which may burden
      biobanks. This study aimed to estimate the costs of gaining certification and
      maintaining certification (i.e., committing extra resources to continue
      standards) for three cancer biobanks participating in a biobank certification
      program in New South Wales, Australia. To gather cost data for a range of cancer
      biobanks, we recruited three with different full time equivalent (FTE) staff
      levels (1.0-3.0), recognizing FTE staff level as an indicator of resources and
      operating scale. In extended interviews with staff, we gathered biobanks'
      expected costs in obtaining and annually maintaining certification. The biobank
      with the highest staff level reported the lowest expected costs in gaining
      certification, due to the strong prealignment of its present operations with
      certification requirements. The other biobanks expected higher costs as their
      operations required greater adjustments. Overall, relative costs of gaining
      certification were between 2% and 6% of current total annual wage costs. To the
      authors' knowledge, this is the first such costing study of a biobank
      certification program. Supplementary Data include the interview schedule that
      other biobanks may use to estimate their own economic certification costs.

PMID- 29215913
TI  - High-Content Screening Comparison of Cancer Drug Accumulation and Distribution in
      Two-Dimensional and Three-Dimensional Culture Models of Head and Neck Cancer.
AB  - High cancer drug development attrition rates have provoked considerable debate
      about whether the two-dimensional tumor growth inhibition high-throughput
      screening assays used in pre-clinical lead discovery adequately reflect solid
      tumor complexity. We used automated high-content screening image acquisition and
      analysis methods to compare fluorescent drug uptake, accumulation, and
      distribution in Cal33 and FaDu head and neck cancer (HNC) monolayer and
      multicellular tumor spheroid (MCTS) models. Ellipticine, idarubicin,
      daunorubicin, and doxorubicin were studied because of their fluorescent
      properties and broad anti-tumor activities. HNC MCTSs were generated in 384-well
      ultra-low attachment plates where compound exposure, image acquisition, and
      analysis could be performed in situ. Fluorescent drug accumulation in Cal33
      monolayer and MCTS cultures was linear with respect to concentration, and
      appeared to achieve steady-state levels within 10-15 min of drug exposure, which
      were maintained through 30-45 min. Drug accumulation in monolayers was
      independent of cell number and/or density, and every cell achieved uniform drug
      concentrations. In MCTSs, however, drug accumulation increased as the number of
      cells and sizes of the MCTSs became bigger. Drugs exhibited restricted
      penetration and distribution gradients, accumulating preferentially in cells in
      the outer layers of MCTSs relative to those in the inner cores. Cal33 monolayers
      were 6-, 20-, 10-, and 16-fold more sensitive than MCTSs to growth inhibition by
      ellipticine, idarubicin, daunorubicin, and doxorubicin, respectively. In Cal33
      MCTSs exposed to ellipticine or doxorubicin for 24 h, MCTSs were smaller and
      although they still exhibited drug penetration and distribution gradients, the
      fluorescent intensity difference between outer and inner cells was reduced. After
      a 24 h exposure, both drugs had penetrated throughout FaDu MCTSs, consistent with
      drug-induced death of peripheral cell layers enhancing drug penetration. The
      increased resistance of MCTS cultures and their ability to recapitulate drug
      penetration and distribution gradients argues strongly for the deployment of
      these more physiological models in cancer lead discovery. MCTSs have the
      potential to enhance the correlation between in vitro potencies and in vivo
      efficacy, and ultimately may lead to improved cancer drug approval rates.

PMID- 29215914
TI  - Feasibility and effectiveness of a parenting programme for Mexican parents of
      children with acquired brain injury-Case report.
AB  - BACKGROUND: Acquired brain injury (ABI) during childhood typically causes
      behaviour problems in the child and high levels of stress in the family.
      OBJECTIVES: (1) To investigate the feasibility and effectiveness of a parenting
      programme to: improve behaviour and self-regulation (SR) in Mexican children with
      ABI, enhance parenting skills, and decrease parental stress in parents of
      children with ABI; (2) to explore the impact of parent SR on child. METHODS: Case
      study design with four participants post-ABI, aged 7-12 years, recruited in
      Mexico City. A parenting programme (Signposts for Building Better Behaviour) was
      delivered and provided parents with strategies to manage child behaviour. Child
      behaviour, child self-regulation, parental stress and parenting practices were
      measured before, immediately post-intervention, and three months post
      intervention. RESULTS: At immediate and three months post-intervention
      improvements in parenting skills, reduction in parental stress, and improvement
      in child behaviour were identified. CONCLUSIONS: The programme is feasible in a
      Mexican population and was effective in improving parenting skills and reducing
      stress in parents of children with ABI, as well as improving child behaviour and
      behavioural SR. These domains continue improving three months after the
      intervention. The improvements in challenging behaviour at home did not transfer
      to the school environment.

PMID- 29215915
TI  - Perspectives on the relevance of the circadian time structure to workplace
      threshold limit values and employee biological monitoring.
AB  - The circadian time structure (CTS) and its disruption by rotating and nightshift
      schedules relative to work performance, accident risk, and health/wellbeing have
      long been areas of occupational medicine research. Yet, there has been little
      exploration of the relevance of the CTS to setting short-term, time-weighted, and
      ceiling threshold limit values (TLVs); conducting employee biological monitoring
      (BM); and establishing normative reference biological exposure indices (BEIs).
      Numerous publications during the past six decades document the CTS substantially
      affects the disposition - absorption, distribution, metabolism, and elimination -
      and effects of medications. Additionally, laboratory animal and human studies
      verify the tolerance to chemical, biological (contagious), and physical agents
      can differ extensively according to the circadian time of exposure. Because of
      slow and usually incomplete CTS adjustment by rotating and permanent nightshift
      workers, occupational chemical and other contaminant encounters occur during a
      different circadian stage than for dayshift workers. Thus, the intended
      protection of some TLVs when working the nightshift compared to dayshift might be
      insufficient, especially in high-risk settings. The CTS is germane to employee BM
      in that large-amplitude predictable-in-time 24h variation can occur in the
      concentration of urine, blood, and saliva of monitored chemical contaminants and
      their metabolites plus biomarkers indicative of adverse xenobiotic exposure. The
      concept of biological time-qualified (for rhythms) reference values, currently of
      interest to clinical laboratory pathology practice, is seemingly applicable to
      industrial medicine as circadian time and workshift-specific BEIs to improve
      surveillance of night workers, in particular. Furthermore, BM as serial
      assessments performed frequently both during and off work, exemplified by
      employee self-measurement of lung function using a small portable peak expiratory
      flow meter, can easily identify intolerance before induction of pathology.

PMID- 29215917
TI  - Breaking the cycle of opioid use disorder with Ibogaine.

PMID- 29215916
TI  - New and incremental FDA black box warnings from 2008 to 2015.
AB  - BACKGROUND: The boxed warning (also known as 'black box warning [BBW]') is one of
      the strongest drug safety actions that the U.S. Food & Drug Administration (FDA)
      can implement, and often warns of serious risks. The objective of this study was
      to comprehensively characterize BBWs issued for drugs after FDA approval.
      METHODS: We identified all post-marketing BBWs from January 2008 through June
      2015 listed on FDA's MedWatch and Drug Safety Communications websites. We used
      each drug's prescribing information to classify its BBW as new, major update to a
      preexisting BBW, or minor update. We then characterized these BBWs with respect
      to pre-specified BBW-specific and drug-specific features. RESULTS: There were 111
      BBWs issued to drugs on the US market, of which 29% (n = 32) were new BBWs, 32%
      (n = 35) were major updates, and 40% (n = 44) were minor updates. New BBWs and
      major updates were most commonly issued for death (51%) and cardiovascular risk
      (27%). The new BBWs and major updates impacted 200 drug formulations over the
      study period, of which 64% were expected to be used chronically and 58% had
      available alternatives without a BBW. CONCLUSIONS: New BBWs and incremental
      updates to existing BBWs are frequently added to drug labels after regulatory
      approval.

PMID- 29215918
TI  - Downregulation of miR-335-5p by Long Noncoding RNA ZEB1-AS1 in Gastric Cancer
      Promotes Tumor Proliferation and Invasion.
AB  - Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and
      prognostic biomarkers in several cancers, including gastric cancer (GC). In this
      study, we investigate the role of lncRNA ZEB1 antisense1 (ZEB1-AS1) on GC
      progression. In the present study, we found that ZEB1-AS1 expression was
      upregulated in GC tissues and cell lines. High ZEB1-AS1 expression was
      significantly correlated with advanced TNM stage, lymph node metastasis, and poor
      overall survival in GC patients. ZEB1-AS1 suppression reduced GC cell
      proliferation and invasion in vitro. Tumor formation assay in nude mice showed
      that ZEB1-AS1 inhibition suppressed GC cell growth. Quantitative real-time PCR
      showed that miR-335-5p expression was downregulated and negatively correlated
      with ZEB1-AS1 expression in GC tissues. And miR-335-5p expression was directly
      regulated by ZEB1-AS1. Furthermore, we found that inhibition of miR-335-5p
      abrogated the suppression of proliferation and invasion of GC cells induced by
      ZEB1-AS1 depletion. Collectively, ZEB1-AS1 is critical for the proliferation and
      invasion of GC cells by regulating miR-335-5p. Our findings indicated that ZEB1
      AS1 might offer potential novel therapeutic targets for GC patients.

PMID- 29215919
TI  - Distribution and morphology of ghrelin immunostained cells in the adrenal gland
      of the African ostrich.
AB  - Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor. We
      investigated the distribution and morphological characteristics of ghrelin
      immunopositive (ghrelin-ip) cells in the African ostrich adrenal gland. We found
      that the adrenal gland of the African ostrich consisted of three parts: capsule,
      inter-renal tissue and chromaffin cells. The inter-renal tissue and chromaffin
      cells interdigitated irregularly. The inter-renal tissue consisted of a
      peripheral zone and a central inner zone. The peripheral zone could be divided
      into an outer subcapsular zone and an inner zone. The subcapsular zone cells were
      arranged as a bow, while the inner area cells formed cords that were
      perpendicular to the capsule. The central inner zone exhibited irregular clumps
      and the cells were morphologically similar to chromaffin cells. Ghrelin-ip cells
      were located throughout the adrenal gland except the capsule. The majority of
      ghrelin-ip cells were found among the chromaffin cells. The number of ghrelin-ip
      cells in the inter-renal tissue decreased gradually from the central inner zone,
      to the inner zone to the subcapsular zone. The ghrelin-ip cells were oval or
      irregular in shape and exhibited cytoplasmic staining. Our findings suggest that
      ghrelin may play a role in regulating adrenal hormone secretion in the African
      ostrich.

PMID- 29215920
TI  - Effects of genetic variants of ST8SIA2 and NCAM1 genes on seasonal mood changes
      and circadian preference in the general population.
AB  - ST8SIA2 and NCAM1 are functionally related genes forming polysialic acid (PSA) -
      neural cell adhesion molecule (NCAM) complex in suprachiasmatic nucleus (SCN),
      the regulating site of circadian biological rhythm. In this study, the
      relationship of ST8SIA2 and NCAM1 with circadian and seasonal rhythms of human
      behavior was explored. Subjects were 261 healthy Korean adults who were free of
      any history of clinically significant psychiatric symptoms. The phenotypes were
      circadian preference and seasonal change of mood and behavior (seasonality)
      measured by the Composite Scale of Morningness and the Seasonal Pattern
      Assessment Questionnaire, respectively. Thirty-four single nucleotide
      polymorphisms (SNPs) across the ST8SIA2 region and 15 SNPs of NCAM1 were
      analyzed. A nominally significant association with seasonality and circadian
      preference was observed in 21 variants of both genes. After corrections for
      multiple testing, associations of 8 SNPs of ST8SIA2 and 2 SNPs of NCAM1 with
      seasonality remained significant. Some of these SNPs were also associated with
      psychiatric disorders in previous studies. This study demonstrated a meaningful
      and/or suggestive evidence of association between behavioral phenotypes
      reflecting human biological rhythm and two interplaying genes involved in the
      plasticity of SCN's neuronal network.

PMID- 29215921
TI  - Authors reply to Letter to the Editor- In Response to: "Smit D, Meyer D, Maritz
      J, et al. Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine
      the Role of Epstein-Barr Virus in Uveitis".

PMID- 29215923
TI  - Sulfide-Stimulation of Oxygen Consumption Rate and Cytochrome Reduction in Gills
      of the Estuarine Mussel Geukensia demissa.
AB  - Organisms, such as the mussel Geukensia demissa, that inhabit high-sulfide
      sediments have mechanisms that impede sulfide poisoning of aerobic respiration.
      Oxygen consumption rates (nO2) of excised ciliated gills from freshly collected
      G. demissa were stimulated 3-fold at sulfide concentrations between 200 and 500
      MUM and remained stimulated at 1000 MUM. Maintenance of mussels in sulfide-free
      conditions resulted in less stimulation of gill nO2 at <500 MUM sulfide and
      inhibition between 500 and 1000 {mu}M sulfide. Gills of Mytilus galloprovincialis
      from a sulfide-free environment were inhibited by {ge}200 MUM sulfide. These
      results indicate that sulfide stimulation of nO2 may be correlated to
      environmental exposure to sulfide. Serotonin, a neurohormonal stimulant of
      ciliary beating, further increased sulfide-stimulated nO2, possibly in support of
      energy demand. Sulfide-stimulated nO2 was negligible in boiled gills and was 61%
      inhibited by cyanide, implicating the participation of mitochondrial electron
      flux. Mitochondrial cytochromes c and oxidase oxidation/ reduction state changed
      little at <500 MUM sulfide, but reduction occurred at 500-2000 MUM sulfide,
      suggesting that although cytochrome oxidation/reduction state may be regulated in
      the face of increased electron flux, regulation may fail at inhibitory sulfide
      levels. Sulfide-stimulated nO2 may represent a detoxification mechanism in G.
      demissa.

PMID- 29215922
TI  - APTM, a Thiophene Heterocyclic Compound, Inhibits Human Colon Cancer HCT116 Cell
      Proliferation Through p53-Dependent Induction of Apoptosis.
AB  - To evaluate the in vitro anticancer activity and to investigate the mechanism of
      action of a thiophene heterocyclic compound, [3-Amino-5-[(2,6
      dimethylphenyl)amino]-4-(phenylsulfonyl)-2-thienyl](4-fluorophenyl)methanone
      (APTM) against human colon cancer HCT116 cells. Sulforhodamine B assay and colony
      formation assay for cell proliferation assay; propidium iodide (PI) staining for
      cell cycle profile analysis; Hoechst staining; annexin V-FITC/PI double staining
      and Western blotting for apoptosis assay. APTM inhibits the growth of HCT116
      cells dose and time dependently. The growth inhibitory effect of APTM on HCT116
      cells was associated with induction of apoptosis but not cell cycle arrest. Also,
      the isogenic cell depletion of p53 was resistant to APTM-induced apoptosis and
      thus grows relatively better than the wild-type cells. The anticancer effect of
      APTM resulted from p53-dependent induction of apoptosis. Also, APTM is a
      promising lead compound for the treatment of human colon cancer.

PMID- 29215924
TI  - Effects of Hypoxia and Low-Frequency Agitation on Byssogenesis in the Freshwater
      Mussel Dreissena polymorpha (Pallas).
AB  - The effect of variations in PO2 and agitation rate on byssogenesis, motility, and
      survival of the zebra mussel (Driessena polymorpha) was investigated. Mussels
      exposed to a PO2 {le} 15.4 torr exhibited increased mortality, reduced motility,
      and significant suppression of byssogenesis. At 7.7 and 15.4 torr, mean survival
      times were 5.2 and 5.8 days, maximum survival times being 15 and 16 days,
      respectively. After 21 days at a PO2 of 23.1 torr, sample mortality was 33.3% and
      declined to 18.2% at 30.9 torr. There was no mortality at full air O2 saturation
      (~ 154.3 torr). Adult zebra mussels exhibited the highest rate of byssogenesis in
      still water (0 cycles per minute [CPM]). Rate of byssogenesis progressively
      decreased as agitation rate increased. At 30 and 40 CPM, rate of byssal thread
      production was significantly lower than at 0 CPM. After 21 days, means of 58.6
      and 44.8 byssal threads/mussel were found in the byssal mass of specimens exposed
      to 30 and 40 CPM, respectively, significantly fewer than the mean of 92.7
      threads/mussel recorded in still water. Suppression of byssogenesis in D.
      polymorpha under hypoxic conditions is a response similar to that reported for
      the marine mytilid Mytilis edulis; however, suppression of byssogenesis with
      elevated agitation rate is the opposite response to that reported for M. edulis.

PMID- 29215925
TI  - Antibacterial Properties of Isolated Amoebocytes From the Sea Anemone Actinia
      equina.
AB  - The antimicrobial defenses of anthozoans were investigated in vitro by extracting
      amoebocytes from the mesenteric filaments of the beadlet anemone, Actinia equina,
      and testing for their ability to phagocytose and kill the gram-negative bacterium
      Psychrobacter immobilis. Only the hyaline amoebocytes exhibited phagocytosis in
      vitro, with about 40% seen to ingest one or more bacteria over 45 min. Mixed
      cultures of viable amoebocytes were further found to produce O2- ions and other
      reactive oxygen species (ROS) after stimulation with phorbol myristate acetate or
      lipopolysaccharide. Co-incubation of viable amoebocytes with P. immobilis for 3 h
      in vitro resulted in reduced growth of the bacterium compared to saline-incubated
      bacteria, but because the growth of P. immobilis was also impaired by lysed
      control amoebocytes, the contribution made to bacterial killing by ROS could not
      be evaluated. Instead, as confirmed by additional experiments using lysate
      supernatants of the amoebocytes, it appears that the cells contain soluble
      bactericidal factors. The nature of these agents is at present unknown, although
      preliminary tests indicate that killing is not mediated by lysozyme.

PMID- 29215926
TI  - Madreporite Function and Fluid Volume Relationships in Sea Urchins.
AB  - An effort was made to demonstrate an influx of seawater through the madreporites
      of sea urchins and to evaluate how such an influx, along with osmotic differences
      and other factors, could contribute to fluid homeostasis. Fluorescent microbeads
      placed in the medium of Strongylocentrotus droebachiensis were taken up into the
      pore canals and stone canal and distributed (in small numbers) to the distal tube
      feet, confirming a slow bulk inflow of seawater through the madreporite, where it
      is partially purified. Probably none of this fluid stream is diverted to the
      perivisceral coelom (as it is in asteroids), since experiments with
      Strongylocentrotus pallidus showed no significant movement of a soluble
      fluorescent tracer into that compartment. The osmotic concentrations of the
      perivisceral coelomic fluids in these two species, and in Strongylocentrotus
      franciscanus, were higher than that of ambient seawater by 2.66 +/- 0.39 mosmol
      kg-1 (mean +/- SE). That small hyperosmoticity, along with the net hydrostatic
      pressure differences induced by the flexing peristome, probably stabilizes body
      fluid volume. Likewise, fluid in the tube feet of S. franciscanus is elevated by
      7.94 +/- 1.04 mosmol kg-1 above seawater, which should contribute to their
      inflation. Blockage of the madreporite does not lead to an obviously reduced
      activity of the tube feet, but over the long term, an influx through the
      madreporite is necessary. Specimens of S. droebachiensis with an obstructed
      madreporite, fed ad libitum, had significantly (P < 0.006) reduced gut contents
      vs controls after 28 days, indicating impaired movement or feeding; and the body
      weights (i.e., volumes) of unfed specimens were significantly (P < 0.013) more
      reduced after 21 days. Compared to starfish, the rigid test of sea urchins
      reduces the need for an influx of seawater through the madreporite, but some
      small admission is still essential.

PMID- 29215927
TI  - Evidence for Intercellular Coupling and Connexin-like Protein in the Luminescent
      Endoderm of Renilla koellikeri (Cnidaria, Anthozoa).
AB  - Gap junction plaques are abundant in Hydrozoa, where they play an important role
      in signal propagation through epithelia and nerve nets, but they have not been
      found in the two other classes of Cnidaria, the Scyphozoa and the Anthozoa. Here
      several lines of evidence are presented that point to the existence of
      intercellular coupling in tissues of the anthozoan Renilla koellikeri, especially
      in the luminescent endoderm. Dye-exchange experiments show that calcein vital
      stains spread between cultured cells after their reassociation. Polyp
      luminescence evoked by KCI depolarization, electrical stimulation, or {beta}
      adrenergic agonists was largely and reversibly suppressed in the presence of the
      gap junction uncouplers octanol, heptanol, and low pH sodium acetate. A
      connexin43-like protein was isolated on Western blots of R. koellikeri membrane
      extracts by using a monoclonal connexin-43 antibody. Loading this antibody in R.
      koellikeri tissues resulted in the suppression of luminescence evoked by
      electrical stimulation. Immunohistochemical investigations using this antibody
      revealed mostly punctate immunostaining associated with endodermal cells of the
      luminescent tissue and with the mesogleal nerve net. Electron microscopic
      observations confirmed the absence of conventional gap junction plaques in these
      tissues, but revealed the presence of tiny zones of close membrane apposition
      between light-emitting and other endodermal cells, with gaps of 2-4 nm. Taken
      together, these results are consistent with the notion of the existence in R.
      koellikeri of intercellular coupling (1) involved in local transmission of
      luminescence signals, and (2) mediated by connexin43-based connexons that are not
      assembled into typical gap junction plaques.

PMID- 29215928
TI  - Chemical Induction of Larval Settlement Behavior in Flow.
AB  - The ability of dissolved chemical cues to induce larval settlement from the water
      column has long been debated. Through computer-assisted video motion analysis, we
      quantified the movements of individual oyster (Crassostrea virginica) larvae in a
      small racetrack flume at free-stream flow speeds of 2.8, 6.2, and 10.4 cm/s. In
      response to waterborne chemical cues, but not to seawater (control), oyster
      larvae moved downward in the water column and swam in slow curved paths before
      attaching to the flume bottom. Effective stimuli were adult-oyster-conditioned
      seawater (OCW) and a synthetic peptide analog (glycyl-glycyl-L-arginine) for the
      natural cue. The chemically mediated behavioral responses of oyster larvae in
      flow were essentially identical to those responses previously reported in still
      water. Our experimental results therefore demonstrate the capacity of waterborne
      cues to evoke settlement behavior in oyster pediveligers under varying
      hydrodynamic conditions.

PMID- 29215929
TI  - Metabolism of Gemmules From the Freshwater Sponge Eunapius fragilis During
      Diapause and Post-Diapause States.
AB  - Post-diapause gemmules of the freshwater sponge Eunapius fragilis remained
      quiescent when maintained at 5 degrees C. Germination occurred within 48 to 72 h
      following warming to 20 degrees -23 degrees C, culminating with the emergence of
      a new sponge from the collagenous capsule. Both heat dissipation and oxygen
      consumption climbed steadily during germination and eventually reached 600% of
      the starting values. By comparison, energy flow was much lower over the same
      period of time in diapausing gemmules, clearly demonstrating metabolic depression
      during diapause. The calorimetric:respirometric (CR) ratio increased
      significantly from -354 kJ/mol O2 to -541 kJ/mol O2 between hours 3.5 and 56.5 of
      germination, with an average value across this period of about -495 kJ/mol O2.
      The low CR ratio at hour 12.5 (-374 +/- 21; +/- 1 SE, n = 3) was statistically
      below the oxycaloric equivalent, which suggests that gemmules may have
      experienced hypoxia during the more than 3 months of storage at 5 degrees C prior
      to experiments. The increase in metabolism during germination could be blocked by
      perfusing the gemmules with nitrogen-saturated medium (nominally oxygen free).
      Developing gemmules were able to survive oxygen limitation for several hours at
      least; during that time energy flow was depressed to 6% of normoxic values.
      During germination, the range of values was 3.5 to 4.0 nmol/mg protein for ATP,
      0.2 to 0.4 nmol/mg protein for ADP, and 0.5 to 0.8 nmol/mg protein for AMP.
      Because ATP was high even before gemmules were warmed to room temperature, it is
      unlikely that levels were severely compromised during the diapause condition.

PMID- 29215930
TI  - Morphological Evidence for a Chitin-Like Glycoprotein in Penaeid Hatching
      Envelopes.
AB  - When chitin hydrolytic enzymes (chitinase and N-acetylglucosaminidase) were used
      as treatment during formation of the hatching envelope (HE) of the penaeid shrimp
      Sicyonia ingentis, results indicated the presence of carbohydrate moieties in the
      envelope. Eggs exposed to these enzymes had abnormal HEs that might elevate and
      often collapsed. The finding that chitin synthase inhibitors (tunicamycin,
      nikkomycin Z, and polyoxin D) also interfered with normal HE formation is further
      evidence for a carbohydrate component. The application of these synthase
      inhibitors resulted in more fragile envelopes that elevated and collapsed or were
      easily lost during processing. Similar results were seen in the absence of
      divalent ions (magnesium and calcium) considered critical for normal chitin
      formation. This morphological evidence is indicative of a chitin-like, linked
      carbohydrate in the HE of Sicyonia ingentis.

PMID- 29215931
TI  - Sources of Energy for Increased Metabolic Demand During Metamorphosis of the
      Abalone Haliotis rufescens (Mollusca).
AB  - Pelagic, lecithotrophic (nonfeeding) larvae of the red abalone (Haliotis
      rufescens) settle and subsequently metamorphose into benthic juveniles capable of
      feeding on particulate food. Thus, metamorphosis must be fueled by either
      endogenous reserves or a nonparticulate food source such as dissolved organic
      material (DOM) in seawater. The metabolic rates (measured as oxygen consumption)
      of abalone larvae were found to increase by an average of 3- to 5-fold from the
      larva to early juvenile stage. The total cost of development from embryo to
      juvenile measured for three cultures ranged from 41.6 mJ to 55.0 mJ. Meeting this
      cost would require 1.3 to 1.7 {mu}g of biomass (ash-free dry mass), which is
      similar to the initial biomass of the spawned oocyte at 1.36 +/- 0.04 {mu}g (mean
      of four cultures). However, there was no net loss of biomass during development
      from the oocyte to the juvenile. The uptake of alanine and glucose from seawater
      by larvae and juveniles could provide one-third of the organic material required
      to supply metabolism, even if the transporters were only operating at 20% of
      their maximum capacity throughout development. For larvae undergoing
      metamorphosis (between 6- and 9-days-old) the proportion of total metabolic
      demand supplied using aerobically catabolized biomass was only 39%. The higher
      metabolic rates of metamorphosis are met only in part by consuming stored
      endogenous reserves. Concomitant with an increase in mass-specific metabolic rate
      during metamorphosis, the maximal capacity (Jmax) for the transport of dissolved
      alanine from seawater increased 3-fold, from 61.2 +/- 1.9 (SE) to 182.0 +/- 49
      pmol alanine individual-1 h-1. The majority (range: 61% to 100%) of the energy
      requirements of larval and early juvenile development of H. rufescens could be
      supplied by input of DOM from the environment. Measurements of transport rates of
      amino acids and sugars by these animals, and calculations of the energy input
      from these substrates, indicate that the cumulative transport of DOM from
      seawater during development to the early juvenile stage could supply an amount of
      energy equivalent to the initial maternal endowment of energy reserves to the
      oocyte of this lecithotrophic species.

PMID- 29215932
TI  - Carbohydrate Mobilization During Germination of Post-Diapausing Gemmules of the
      Freshwater Sponge Eunapius fragilis.
AB  - Post-diapausing gemmules of the freshwater sponge Eunapius fragilis were found to
      contain sorbitol and glycogen as their primary carbohydrates. The sorbitol
      probably acts to increase the tolerance of the gemmules to freezing and
      desiccation. During germination, average sorbitol levels--measured as micromoles
      of sorbitol per gram of fresh weight of gemmule tissue (MUmol/gfw)--declined from
      a control value of 36 MUmol/gfw to about 4 MUmol/gfw. Concomitantly, average
      glycogen levels increased from a control value of 29 MUmol/gfw to a steady-state
      level of 62 MUmol/gfw. It is probable that glycogen is being synthesized at the
      expense of sorbitol. The breakdown of sorbitol was associated with an increase in
      the activity of sorbitol dehydrogenase from undetectable levels in dormant
      gemmules to a maximum of 0.2 MUmol/ min . mg protein after 30 h of exposure to 20
      degrees C. Aldose reductase activity remained constant throughout germination.
      These data support the hypothesis that the decrease in sorbitol levels is the
      result of an increase in the rate of catabolism by sorbitol dehydrogenase. The
      total activity of glycogen synthase did not change during germination; however,
      the activity of glucose-6-phosphate-dependent glycogen synthase was about 18
      times greater than the activity of glucose-6-phosphate-independent glycogen
      synthase. Total glycogen phosphorylase activity increased from about 1.6
      nmol/min.mg protein to 3.6 nmol/min.mg protein during germination. At the same
      time, however, the percentage of glycogen phosphorylase a decreased from almost
      100% to about 84%. This decrease would attenuate the apparent increase in
      activity. cAMP levels remained constant throughout germination. The observed
      changes in the level of glycogen in the gemmules are not simply due to changes in
      the activity of either glycogen phosphorylase or glycogen synthase.

PMID- 29215936
TI  - Eov Toc.

PMID- 29215937
TI  - Orthorexia Nervosa: A Review of the Literature.
AB  - BACKGROUND: The phenomenon of orthorexia nervosa (ON) has been noted by
      clinicians since 1996 and described in the scientific literature, and yet there
      is no formal recognition of ON as a psychiatric diagnosis. OBJECTIVE: Review the
      latest available literature regarding diagnoses similarities, presentation
      uniqueness, assessment/assessment tools, and suggested treatments of ON.
      METHOD/DESIGN: A literature search of four databases focusing on articles
      published between 2000 and 2016 was conducted to evaluate the status of the
      literature on Orthorexia. RESULTS: Among the 15 articles selected for this
      review, similarities with other psychiatric disorders emerged, confusion about
      use of assessment tools existed, and the lack of evidence based treatments for ON
      was pronounced. CONCLUSION: More research is needed to determine the prevalence
      of pathologically unhealthy, obsessive, "self-defined healthy," eating behaviors,
      and to determine if ON is a unique eating disorder or just a subset of another
      disorder.

PMID- 29215933
TI  - A randomized phase II trial of induction chemotherapy followed by cisplatin
      chronotherapy versus constant rate delivery combined with radiotherapy.
AB  - Chronotherapy is no longer a novel concept in cancer treatment after
      approximately 20 years of development. Many clinical trials have provided strong
      supporting evidence that chronomodulated treatment yields better results than a
      traditional dosage regimen. This study aimed to evaluate the adverse reactions,
      effect on immune functions, and therapeutic efficacy of chronomodulated infusion
      versus flat intermittent infusion of cisplatin (DDP) combined with intensity
      modulated radiation therapy (IMRT) in patients with locoregionally advanced
      nasopharyngeal carcinoma (NPC). A total of 148 patients with biopsy-diagnosed
      untreated stage III-IVb NPC were randomly assigned to undergo two cycles of
      chronomodulated infusion (study group) or flat intermittent infusion (control
      group) of DDP (100 mg/m2 on day 1, 21 days/cycle) synchronized with radical
      radiotherapy. Patients in the study group received chronomodulated infusion, with
      peak delivery of DDP at 16:00 pm. Patients in the control group received a
      routine constant rate of infusion. Both groups were treated with the same
      radiotherapy techniques. Over a median follow-up of 20 months, the study group
      had better outcomes for adverse effects and immune functions compared with the
      control group. During the phase of concurrent chemoradiotherapy, the incidence of
      nausea, vomiting, and oral mucositis in the study and control groups was 66.7%
      and 79.5% (p < 0.05), 47.9% and 71.2% (p < 0.05), and 73.9% and 87.7% (p < 0.05),
      respectively. There was no significant difference in 2-year overall survival,
      progression-free survival, and distant metastasis-free survival between the two
      groups (p > 0.05). Chronochemotherapy significantly reduced the incidence of
      adverse reactions and enhanced the tolerance for treatment without affecting
      survival. It is worth mentioning that reduced destruction of immune function is a
      novel area of exploration in chronotherapy research.

PMID- 29215938
TI  - Putting Mental Health Above All-Literally.

PMID- 29215940
TI  - Associate Editors "Issues in Mental Health Nursing" 2017.

PMID- 29215941
TI  - The Role of Wnt/beta-Catenin Signaling Pathway in the Transdifferentiation from
      Periodontal Ligament Stem Cells to Schwann Cells.
AB  - This study was aimed to investigate the role of Wnt/beta-catenin signaling
      pathway in the differentiation from periodontal ligament stem cells (PDLSCs) to
      Schwann cells (SCs) and the possible mechanisms. FzB was applied to inhibit the
      Wnt/beta-catenin signaling pathway of differentiated PDLSCs (dPDLSCs), and then
      immunofluorescence, polymerase chain reaction (PCR), and Western blotting
      analysis were performed to detect SC marker genes and proteins such as S100,
      glial fibrillary acidic protein (GFAP), and P75NTR. Results showed that when the
      Wnt/beta-catenin signaling pathway was inhibited, the expression of S100, GFAP,
      and P75NTR protein significantly decreased in dPDLSCs, p < 0.05, whereas PCR
      results showed that expression of SC myelinogenesis-related genes krox-20, Oct-6,
      P0, and PMP-22 was significantly downregulated at the same time, p < 0.05. These
      results showed that Wnt/beta-catenin signaling pathway participated in the
      differentiation from PDLSCs to SCs, and inhibiting it could inhibit the
      differentiation process.

PMID- 29215942
TI  - Cocktail of Chemical Compounds and Recombinant Proteins Robustly Promote the
      Stemness of Adipose-Derived Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) from somatic cells can be reprogrammed to
      provide an unlimited cell resource showing great potential in disease modeling
      and regenerative medicine. However, the traditional method for reprogramming
      cells into iPSCs using genome-integrating retro- or lenti-viruses remain an
      obstacle for its application in clinical settings. We tried the possibility to
      generate pre-iPSCs from human adipose-derived stem cells (ADSCs) by nongenetic
      reprogramming using recombinant cell-penetrating proteins OCT4/KLF4/SOX2 (PTD
      OKS) and the cocktail of small molecules (VCFZ). Our experimental results
      demonstrated that PTD-OKS in combination with VCFZ (VCFZ+OKS) could significantly
      enhance the stemness of ADSCs and easily get pre-iPSCs after 25 days treatments.
      The pre-iPSCs showed similar morphology to iPSCs, which were positive for
      alkaline phosphatase staining. Furthermore, RT-polymerase chain reaction analysis
      showed that VCFZ+OKS could significantly upregulate the expression of OCT4, KLF4,
      SOX2, and NANOG gene after 25 days treatment. And immunofluorescence staining
      also showed that the protein makers of pluripotent stem cell were positively
      expressed in VCFZ+OKS treated group. Our data suggest that nongenetic-mediated
      reprogramming from ADSCs may be a promising stem cell sources for cell therapy in
      the near future.

PMID- 29215943
TI  - In vivo and ex vivo analyses of amyloid toxicity in the Tc1 mouse model of Down
      syndrome.
AB  - RATIONALE: The prevalence of Alzheimer's disease is increased in people with Down
      syndrome. The pathology appears much earlier than in the general population,
      suggesting a predisposition to develop Alzheimer's disease. Down syndrome results
      from trisomy of human chromosome 21, leading to overexpression of possible
      Alzheimer's disease candidate genes, such as amyloid precursor protein gene. To
      better understand how the Down syndrome context results in increased
      vulnerability to Alzheimer's disease, we analysed amyloid-beta [25-35] peptide
      toxicity in the Tc1 mouse model of Down syndrome, in which ~75% of protein coding
      genes are functionally trisomic but, importantly, not amyloid precursor protein.
      RESULTS: Intracerebroventricular injection of oligomeric amyloid-beta [25-35]
      peptide in three-month-old wildtype mice induced learning deficits, oxidative
      stress, synaptic marker alterations, activation of glycogen synthase kinase
      3beta, inhibition of protein kinase B (AKT), and apoptotic pathways as compared
      to scrambled peptide-treated wildtype mice. Scrambled peptide-treated Tc1 mice
      presented high levels of toxicity markers as compared to wildtype mice. Amyloid
      beta [25-35] peptide injection in Tc1 mice induced significant learning deficits
      and enhanced glycogen synthase kinase-3beta activity in the cortex and expression
      of apoptotic markers in the hippocampus and cortex. Interestingly, several
      markers, including oxidative stress, synaptic markers, glycogen synthase kinase
      3beta activity in the hippocampus and AKT activity in the hippocampus and cortex,
      were unaffected by amyloid-beta [25-35] peptide injection in Tc1 mice.
      CONCLUSIONS: Tc1 mice present several toxicity markers similar to those observed
      in amyloid-beta [25-35] peptide-treated wildtype mice, suggesting that
      developmental modifications in these mice modify their response to amyloid
      peptide. However, amyloid toxicity led to severe memory deficits in this Down
      syndrome mouse model.

PMID- 29215944
TI  - FERONIA/FER-like receptor kinases integrate and modulate multiple signaling
      pathways in fruit development and ripening.
AB  - Ripening of fleshy fruits is a complex process that involves dramatic changes in
      color, texture, flavor, and aroma, which is essentially regulated by multiple
      hormone signals. Although the metabolic mechanisms for the regulation of fruit
      development and ripening have been studied extensively, little is known about the
      signaling mechanisms underlying this process. FERONIA has been increasingly
      suggested to be implicated in multiple signaling pathways. In a recent
      publication, we showed that a FERONIA/FER -like receptor kinase, FaMRLK47, playes
      an important role in the regulation of fruit ripening in strawberry (Fragaria *
      ananassa, a typical non-climacteric fruit) fruit. Over-expression orRNAi-mediated
      down regulation of FaMRLK47 caused a delay or acceleration, respectively, of
      fruit ripening progress. Meanwhile, overexpression orRNAi-mediated down
      regulation of FaMRLK47 caused a decrease or increase, respectively, in the ABA
      induced expression of a series of ripening-related genes. More recently, we also
      found that MdFERL1, a FERONIA/FER-like receptor kinase in tomato plant, was
      implicated in the regulation of tomato fruit ripening via modulating ethylene
      production. We propose that FERONIA/FER-like receptor kinases may function to
      regulate fruit development and ripening via integrate multiple signaling pathways
      in both climacteric and non-climacteric fruits.

PMID- 29215945
TI  - The adverse effects of chronic low-dose exposure to nonylphenol on type 2
      diabetes mellitus in high sucrose-high fat diet-treated rats.
AB  - OBJECTIVES: Although it has been shown that exposure to environmental endocrine
      disruptors (EDCs) has been implicated as a potential risk factor for metabolic
      disease, information on adverse effect of chronic low-dose exposure to
      nonylphenol (NP), on the development and progress of type 2 diabetes mellitus
      (T2DM) is scarce. NP, as an EDC, is a ubiquitous degradation product of
      nonylphenol polyethoxylate (NPE) that is primarily used in cleaning and
      industrial processes. METHOD: Eighty Sprague-Dawley rats were assigned into 8
      groups (n = 10 per group): rats fed a normal-diet (ND) as the control (C-ND);
      rats fed a normal diet and were gavaged with NP at a dose level of 0.02
      MUg/kg/day (NP-L-ND), 0.2 MUg/kg/day (NP-M-ND) or 2 MUg/kg/day (NP-H-ND),
      respectively; rats fed a high-sucrose/high-fat diet (HSHFD) as the HSHFD control
      (C-HSHFD); rats fed a HSHFD and were gavaged with NP at a dose level of 0.02
      MUg/kg/day (NP-L-HSHFD), 0.2 MUg/kg/day (NP-M-HSHFD) or 2 MUg/kg/day (NP-H
      HSHFD), respectively. RESULT: On day 180, the rats in the groups treated with NP
      M-HSHFD and NP-H-HSHFD showed significant increases in body weight (p < 0.05) in
      comparison with the C-ND group. Fast blood glucose (FBG) level in the NP-M-HSHFD
      and NP-H-HSHFD groups was higher than that in the C-ND group (F = 96.17, p <
      0.001). The fast serum insulin (FINS) level of rats was lower in both the NP-M
      HSHFD and NP-H-HSHFD groups compared with the C-ND group (F = 145.56, p < 0.001).
      Serum leptin (LEP) level in both the NP-M-HSHFD and NP-H-HSHFD groups was lower
      when compared with the C-ND group (F = 34.62, p < 0.001). The effect of NP at the
      dose level of 0.2 MUg/kg/day on FBG, serum FINS and LEP levels in rats was
      greatest among the treatment groups (p < 0.05). Oral glucose tolerance test
      showed increased area under the curve (AUC) in treatment groups at week 12 (p <
      0.05). A decrease of pancreatic islet numbers and size was exhibited in the
      pancreatic tissue of NP-M-HSHFD and NP-H-HSHFD treated rats compared with C-ND
      treated rats. Co-exposure to NP and HSHFD causes inflammatory changes
      histologically. CONCLUSION: Chronic low-dose exposure to NP might induce impaired
      glucose tolerance, which further lead to insulin resistance, and pancreatic beta
      cell insulin secretion deficiency, ultimately increase the risk of T2DM.
      Moreover, additive toxic effects of NP and HSHFD on pancreatic beta-cell function
      and glucose metabolism have been identified in rats as well.

PMID- 29215946
TI  - Synthesis of the first novel pyrazole thioglycosides as deaza ribavirin
      analogues.
AB  - This study reports a novel and efficient method for the synthesis of the first
      reported novel class of thiopyrazoles and their corresponding thioglycosides.
      These series of compounds were designed through the reaction of hydrazine
      derivatives with sodium dithiolate salt 2 in EtOH at ambient temperature to give
      the corresponding sodium 5-amino-4-cyano-1H-pyrazole-3-thiolates 4a-d. The latter
      compounds were treated with alpha-acetobromoglucose 6a and alpha
      acetobromogalactose 6b in DMF at ambient temperature to give in an excellent
      yields the corresponding pyrazole S-glycosides 7a-h. Ammonolysis of the pyrazole
      thioglycosides 7a-h afforded the corresponding free thioglycosides 8a-h.

PMID- 29215947
TI  - Co-metabolic degradation of iomeprol by a Pseudomonas sp. and its application in
      biological aerated filter systems.
AB  - The non-ionic water-soluble X-ray contrast agent iomeprol (IOM) enters the water
      supply through sewage treatment plants, which can cause considerable
      environmental harm. In this study, Pseudomonas sp. I-24 (I-24) was tested for its
      ability to remove IOM from water via co-metabolic pathways. The optimum removal
      rate of IOM by I-24 was 38.43% +/- 3.70% when starch served as the source of
      external carbon, and its co-metabolism of IOM conformed to the first-order
      kinetics. The highest activity of intracellular enzyme (degrading enzyme)
      extracted from I-24 was 0.143 +/- 0.005 mU in starch condition. The Michaelis
      constant of the degrading enzyme was found to be 91.08 MUmol L-1. However,
      glucose and maltose showed the best promotive effects on the growth and electron
      transport activity of I-24, indicating that overgrowth may result in competitive
      inhibition and a reduced degradation rate of IOM. Adding I-24 and degrading
      enzymes to biological aerated filters increased IOM removal rates without
      affecting CODMn removal.

PMID- 29215948
TI  - Evaluation of suitable DNA regions for molecular identification of high value
      medicinal plants in genus Kaempferia.
AB  - DNA barcoding coupled high resolution melting (Bar-HRM) is an emerging method for
      species discrimination based on DNA dissociation kinetics. The aim of this work
      was to evaluate the suitability of different primer sets, derived from selected
      DNA regions, for Bar-HRM analysis of species in Kaempferia (Zingiberaceae). Four
      primer pairs were evaluated (rbcL, rpoC, trnL and ITS1). It was observed that the
      ITS1 barcode was the most useful DNA barcoding region overall for species
      discrimination out of all of the regions and primers assessed. Thus, the primer
      pair derived from the ITS1 region was the single most effective region for the
      identification of the tested species, whereas the rbcL primer pair gave the
      lowest resolution. Our Bar-HRM developed here would not only be useful for
      identification of Kaempferia plant specimens lacking essential parts for
      morphological identification but will be useful for authenticating products in
      powdered form of a high value medicinal species Kaempferia parviflora, in
      particular.

PMID- 29215949
TI  - Laparoscopic Retroperitoneal Lymph Node Dissection as a Safe Procedure for
      Postchemotherapy Residual Mass in Testicular Cancer.
AB  - BACKGROUND: To evaluate the feasibility, clinical and perioperative outcomes of
      laparoscopic retroperitoneal lymph node dissection (L-RPLND) in the management of
      patients with germ cell tumors (GCT) and residual post-chemotherapy mass.
      METHODS: We report our experience of 25 patients treated with L-RPLND between
      2008 and 2015. All 25 patients were diagnosed with GCT by primary pathological
      evaluation of the specimens after orchiectomy. All patients received cisplatin
      based chemotherapy. The technique consisted of L-RPLND excision of the residual
      mass using unilateral template dissection. We assessed perioperative data and
      histological findings. RESULTS: Surgery was successfully completed in 24 (96%)
      patients, 1 patient required an open surgery due to intense adhesions of the mass
      to the inferior vena cava. Mean operation time was 213 minutes. Mean blood loss
      was 260 mL. Postoperative complications were upper limb osteomuscular pain in 2
      patients and chylous ascites in 1 patient. Mean postoperative hospital stay was 2
      days. The median residual mass diameter was 3.3 cm (range 1.1-6.6 cm).
      Histopathological findings were necrotic tissue in 9 patients, teratoma in 9
      patients, viable tumor in 6 patients, and Castleman disease in 1 patient. The
      median follow-up was 30 months. Normal antegrade ejaculation was preserved in all
      patients. CONCLUSIONS: Laparoscopic postchemotherapy RPLND is a feasible, safe,
      and highly oncologically efficient procedure, which has the benefits of minimally
      invasive surgery.

PMID- 29215950
TI  - Preparation and characterization of alkaline phosphatase, horseradish peroxidase,
      and glucose oxidase conjugates with carboxylated carbon nano-onions.
AB  - Carbon nanomaterials have emerged as suitable supports for enzyme immobilization
      and stabilization due to their inherently large surface area, high electrical
      conductivity, chemical stability, and mechanical strength. In this paper, carbon
      nano-onions (CNOs) were used as supports to immobilize alkaline phosphatase,
      horseradish peroxidase, and glucose oxidase. CNOs were first functionalized by
      oxidation to generate carboxylic groups on the surface followed by the covalent
      linking of using a soluble carbodiimide as coupling agent. The CNO-enzyme
      conjugates were characterized by transmission electron microscopy and Raman
      spectroscopy. Thermogravimetric analysis revealed a specific enzyme load of ~0.5
      mg of protein per milligram of CNO. The immobilized enzymes showed enhanced
      storage stability without altering the optimum pH and temperatures. These
      properties make the prepared nanobiocatalyst of potential interest in biosensing
      and other biotechnological applications.

PMID- 29215951
TI  - Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in
      Glaucoma Pharmacotherapy.
AB  - Hydrogen sulfide (H2S) is a gaseous transmitter with well-known biological
      actions in a wide variety of tissues and organs. The potential involvement of
      this gas in physiological and pathological processes in the eye has led to
      several in vitro, ex vivo, and in vivo studies to understand its pharmacological
      role in some mammalian species. Evidence from literature demonstrates that 4
      enzymes responsible for the biosynthesis of this gas (cystathionine beta
      synthase, CBS; cystathionine gamma-lyase, CSE; 3-mercaptopyruvate
      sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea,
      iris, ciliary body, lens, and retina. Studies of the pharmacological actions of
      H2S (using several compounds as fast- and slow-releasing gas donors) on anterior
      uveal tissues reveal an effect on sympathetic neurotransmission and the ability
      of the gas to relax precontracted iris and ocular vascular smooth muscles,
      responses that were blocked by inhibitors of CSE, CBS, and KATP channels. In the
      retina, there is evidence that H2S can inhibit excitatory amino acid
      neurotransmission and can also protect this tissue from a wide variety of
      insults. Furthermore, exogenous application of H2S-releasing compounds was
      reported to increase aqueous humor outflow facility in an ex vivo model of the
      porcine ocular anterior segment and lowered intraocular pressure (IOP) in both
      normotensive and glaucomatous rabbits. Taken together, the finding that H2S
      releasing compounds can lower IOP and can serve a neuroprotective role in the
      retina suggests that H2S prodrugs could be used as tools or therapeutic agents in
      diseases such as glaucoma.

PMID- 29215952
TI  - Easy and fast extraction methods to determine organochlorine pesticides in sewage
      sludge, soil, and water samples based at low temperature.
AB  - Organochlorine pesticides present in sewage sludge can contaminate soil and water
      when they are used as either fertilizer or agricultural soil conditioner. In this
      study, the technique solid-liquid extraction with low temperature purification
      was optimized and validated for determination of ten organochlorine pesticides in
      sewage sludge and soil samples. Liquid-liquid extraction with low temperature
      purification was also validated for the same compounds in water. Analyses were
      performed by gas chromatography-mass spectrometry operating in the selective ion
      monitoring mode. After optimization, the methods showed recoveries between 70%
      and 115% with relative standard deviation lower than 13% for all target analytes
      in the three matrices. The linearity was demonstrated in the range of 20 to 70 ug
      L-1, 0.5 to 60 ug L-1, and 3 to 13 ug L-1, for sludge, soil, and acetonitrile,
      respectively. The limit of quantification ranged between 2 and 40 ug kg-1, 1 and
      6 ug kg-1, and 0.5 ug L-1 for sludge, soil, and water, respectively. The methods
      were used in the study of pesticide lixiviation carried out in a poly vinyl
      chlorine column filled with soil, which had its surface layer mixed with sludge.
      The results showed that pesticides are not leached into soil, part of them is
      adsorbed by the sewage sludge (4-40%), and most pesticides are lost by
      volatilization.

PMID- 29215953
TI  - Further insights into the role of NIN-LIKE PROTEIN 7 (NLP7) in root cap cell
      release.
AB  - The root cap protects the root from environmental stress and senses gravity.
      Cells of the last layer of the root cap are shed in a developmentally programmed
      process. We previously showed that the transcription factor NIN-LIKE PROTEIN7
      (NLP7) regulates root cap cell release likely through regulation of CELLULASE5
      (CEL5). Here we provide a supplement to that work. We hypothesized that the nlp7
      mutant has defects in additional root cap functions. We find that neither gravity
      sensing nor expression of a root cap cell identity marker is altered in nlp7 but
      that expression of another cellulase, CEL3, is upregulated. We conclude that NLP7
      control of root cap cell release is largely independent of gravity sensing and
      root cap cell identity.

PMID- 29215954
TI  - Evolution of Various Components of Pain After Laparoscopic Cholecystectomy:
      Importance of Its Prognostication for Effective Pain Control Using a Local
      Anesthetic and for Making a Valid Practical "Discharge Criteria" Model Predicting
      Early Discharge of Patients.
AB  - OBJECTIVES: Pain continues to be the most important limiting factor affecting the
      early discharge of patients after laparoscopic cholecystectomy (LC). Our aim was
      to conduct a randomized case controlled study to predict the evolution of various
      components of postoperative pain by using ropivacaine 0.2% at intraperitoneal and
      intraincisional locations; and to further use this information to make a model
      predicting early discharge of patients. METHODS: Two hundred forty-four patients
      underwent elective four-port LC. Patients were triple blindly randomized. All
      patients received ~23 mL of solution, of which 20 mL was given intraperitoneally
      and ~3 mL was given intraincisionally. Solution was either normal saline or drug
      (0.2% ropivacaine) depending on the group (controls [n = 77], intraperitoneal
      group [n = 80], and intraincisional group [n = 87]). Five different pain scales
      were used for assessment of overall pain. Only those patients with a Visual
      Analog Scale (VAS) <=3, Numeric Rating Scale (NRS) <=3, Visual Descriptor Scale
      (VDS) <= "Slight Pain," Faces Pain Scale-Revised (FPS-R) <=2, and Activity
      Tolerance Scale (ATS) <= "Can Be Ignored" along with absence of use of rescue
      analgesia and shoulder pain were considered for "Discharge Criteria." RESULTS:
      Incisional component of pain was found to be the main component of pain that
      predominated in the immediate postoperative period. However, it declined rapidly
      over 12 hours and was then dominated by the visceral component. Shoulder
      component peaked around the eighth postoperative hour. Seven percent of patients
      in controls could be discharged at the 12th postoperative hour and 18% at the
      24th hour. In the intraperitoneal group, 18% and 61% patients could be discharged
      at the 12th and 24th hour, respectively, as compared with 57% and 78% in the
      intraincisional group using the "Discharge Criteria." "Discharge Criteria" was
      100% effective in predicting patients' acceptance to go home. CONCLUSION: The
      effect of local anesthetic at intraincisional and intraperitoneal sites is
      additive with drug catering to different components of pain. We recommend using
      the "Abbreviated Discharge Criteria" routinely in practice to check for patients'
      eligibility to be discharged.

PMID- 29215955
TI  - Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of
      Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously
      Treated Metastatic Colorectal Cancer: The TERRA Study.
AB  - Purpose Trifluridine/tipiracil (TAS-102) was effective in patients with
      metastatic colorectal cancer (mCRC) in a phase II Japanese trial. This regional
      trial evaluated the efficacy and safety of trifluridine/tipiracil in Asian
      patients with mCRC with or without exposure to biologic therapy. Patients and
      Methods This randomized, double-blind, placebo-controlled, phase III trial was
      conducted at 30 sites in China, the Republic of Korea, and Thailand. Patients >=
      18 years old with histologically or cytologically confirmed adenocarcinoma of the
      colon or rectum and known KRAS status who were refractory or intolerant to two or
      more prior chemotherapy regimens were enrolled. Eligible patients were randomly
      assigned (2:1 ratio; minimization method) to receive trifluridine/tipiracil
      (twice per day orally; 5 days on and 2 days off for 2 weeks, followed by 14 days
      off per cycle) or placebo. The primary end point was overall survival (intent-to
      treat population). Results Between October 16, 2013, and June 15, 2015, 406
      patients were randomly assigned to receive trifluridine/tipiracil (n = 271) or
      placebo (n = 135). Risk of death was significantly lower in the
      trifluridine/tipiracil arm than in the placebo arm (hazard ratio for death, 0.79;
      95% CI, 0.62 to 0.99; log-rank P = .035). Median overall survival was
      significantly longer in the trifluridine/tipiracil than in the placebo arm (7.8
      months [95% CI, 7.1 to 8.8 months] v 7.1 months [95% CI, 5.9 to 8.2 months],
      respectively), for a median survival follow-up time of 13.8 months (95% CI, 13.1
      to 15.3 months) compared with 13.4 months (95% CI, 11.6 to 17.3 months),
      respectively. The incidence of serious adverse events was similar between the
      arms (trifluridine/tipiracil, n = 63 [23.2%]; placebo, n = 32 [23.7%]). No
      treatment-related deaths were reported. Conclusion Trifluridine/tipiracil has a
      statistically significant survival benefit compared with placebo in Asian
      patients with mCRC refractory or intolerant to standard chemotherapies,
      regardless of exposure to biologic therapy. The safety profile is similar to
      previous reports.

PMID- 29215956
TI  - Effect of thrombopoietin receptor agonists on markers of coagulation and P
      selectin in patients with immune thrombocytopenia.
AB  - Thrombopoietin-receptor-agonists (TPO-RA) are effective treatments of immune
      thrombocytopenia (ITP). Previous long-term TPO-RA clinical trials have shown that
      thrombotic events occurred in 6% of TPO-RA-treated ITP patients. To explore the
      increased risk of thrombosis, the effects of TPO-RA on markers of coagulation and
      P-selectin were studied. The study comprised two ITP cohorts and controls. Cohort
      1 included 26 patients with sequential samples acquired before and during
      treatment with TPO-RA. Cohort 2 included a single sample in 18 patients on TPO-RA
      for more than one year. Thrombin generation (endogenous thrombin potential (ETP))
      prothrombin fragments 1 + 2 (F1+2), D-dimer, and plasminogen-activator-inhibitor
      1 (PAI-1) were measured as well as soluble P-selectin (sP-selectin). Sequential
      expression of encoding genes for P-selectin (SELP) and PAI-1 (SERPINE1) was
      determined in four patients in cohort 1. Significantly higher levels of F1+2, D
      dimer, and PAI-1 were found in ITP patients before TPO-RA treatment and in
      patients on long-term TPO-RA treatment than in controls. Pre-treatment levels of
      sP-selectin did not differ from controls. Analysis of longitudinal trends showed
      an increase in platelet count, sP-selectin, and PAI-1 after initiation of TPO-RA,
      followed by gradual decline. Platelet count and sP-selectin remained at higher
      levels throughout the study, whereas PAI-1 did not. Levels of other studied
      parameters did not show significant changes after initiation of treatment.
      Expression of SELP was up-regulated after initiation of TPO-RA, while the
      expression of SERPINE1 showed no significant changes. In conclusion, elevated pre
      treatment levels of F1+2, D-dimer and PAI-1 are compatible with ITP being an
      intrinsically pro-thrombotic condition. After TPO-RA treatment, there were no
      significant changes in markers of coagulation activation or fibrinolysis, except
      for an initial increase in PAI-1 and a significant increase in sP-selectin both
      of which may contribute to increased thrombotic risk associated with TPO-RA
      treatment in ITP.

PMID- 29215957
TI  - Peroral Endoscopic Myotomy with EndoFLIP and Double-Endoscope: Novel Techniques
      for Achalasia in Pediatric Population.
AB  - BACKGROUND: Experience of peroral endoscopic myotomy (POEM) for treatment of
      achalasia in pediatric population is limited with varying techniques in different
      centers. The accurate extent of submucosal tunneling into the gastric cardia and
      the adequacy of myotomy are the important determining factors to success of POEM.
      A majority of studies in pediatric population have described using submucosal dye
      injection for assessing the adequacy of myotomy, however, this is a rather crude
      and inaccurate method. We herein describe the first case of pediatric achalasia
      managed with POEM incorporated with novel combined techniques using EndoFLIP(r)
      (Endoluminal Functional Lumen Imaging Probe) and double endoscope. METHODS:
      Esophagogastric junction (EGJ) was identified with a gastroscope. Before POEM,
      EndoFLIP showed EGJ distensibility index of 1.7 mm2/mmHg. Submucosal tunnel was
      created from the mucosal entry site at midesophagus down and ~3 cm beyond the
      EGJ. Anterior myotomy cutting the circular muscle layer while preserving the
      longitudinal muscle was performed for 8 cm. Double-endoscope technique was used
      to confirm the adequacy of myotomy by inserting a smaller endoscope through
      nostril into stomach and observing the transillumination of the first endoscope
      at the end of submucosal tunnel. After POEM, repeat EndoFLIP measurements
      revealed increased distensibility index to 6.0 mm2/mmHg. Endoscopic examination
      at the end of the procedure showed widely patent EGJ. RESULTS: Eckardt symptoms
      score improved from 9 to 0. At 7 month after POEM, esophagoscopy showed widely
      open EGJ with no esophagitis, and high-resolution esophageal manometry revealed
      normalized lower esophageal sphincter pressure and resting tone. CONCLUSIONS: We
      introduced the intraoperative use of EndoFLIP system that allows real-time
      assessment of EGJ distensibility and immediate treatment effect evaluation.
      Incorporation of double-endoscope POEM was also first described in our pediatric
      patient for ensuring complete gastric myotomy. From our experiences, POEM for
      achalasia in pediatric population appears to have encouraging results similar to
      adult patients.

PMID- 29215958
TI  - Postoperative Complications of Pars Plana Vitrectomy for Diabetic Retinal
      Disease.
AB  - Despite recent advances in the medical management of diabetic retinal disease,
      there remain established indications for vitreoretinal surgery in the treatment
      of severe proliferative diabetic retinopathy. These include non-clearing vitreous
      hemorrhage and tractional retinal detachment. Advances in surgical
      instrumentation, technique, and experience have led to improved visual outcomes,
      as well as a corresponding decrease in the incidence of postoperative
      complications. However, the presence of systemic and ocular factors in diabetic
      patients increases the risk of adverse events compared to non-diabetic
      individuals. This review will focus on the most important postoperative
      complications following pars plana vitrectomy, with specific considerations for
      the diabetic patient.

PMID- 29215959
TI  - Performance intensification of a stirred bioreactor for fermentative biohydrogen
      production.
AB  - In this study, the biohydrogen (bioH2) production of a microbial consortium was
      optimized by adjusting the type and configuration of two impellers, the mixing
      regimen and the mass transfer process (KLa coefficients). A continuous stirred
      tank reactor (CSTR) system, with a nonstandard geometry, was characterized. Two
      different mixing configurations with either predominant axial (PB4 impeller) or
      radial pumping (Rushton impeller) were assessed and four different impeller
      configurations to produce bioH2. The best configuration for an adequate mixing
      time was determined by an ANOVA analysis. A response surface methodology was also
      used to fully elucidate the optimal configuration. When the PB4 impellers were
      placed in best configuration, c/Dt = 0.5, s/Di = 1, the maximum bioH2
      productivity obtained was 440 mL L-1 hr-1, with a bioH2 molar yield of 1.8. The
      second best configuration obtained with the PB4 impellers presented a bioH2
      productivity of 407.94 mL L-1 hr-1. The configurations based on Rushton impellers
      showed a lower bioH2 productivity and bioH2 molar yield of 177.065 mL L-1 hr-1
      and 0.71, respectively. The experiments with axial impellers (PB4) showed the
      lowest KLa coefficient and the highest bioH2 production, suggesting that mixing
      is more important than KLa for the enhanced production of bioH2.

PMID- 29215961
TI  - Analysis of air quality in Dire Dawa, Ethiopia.
AB  - : Ambient air quality was monitored and analyzed to develop air quality index and
      its implications for livability and climate change in Dire Dawa, Ethiopia. Using
      survey research design, 16 georeferenced locations, representing different land
      uses, were randomly selected and assessed for sulfur dioxide (SO2), nitrogen
      dioxide (NO2), carbon dioxide (CO2), carbon monoxide (CO),volatile organic
      compounds (VOCs), and meteorological parameters (temperature and relative
      humidity). The study found mean concentrations across all land uses for SO2 of
      0.37 +/- 0.08 ppm, NO2 of 0.13 +/- 0.17 ppm, CO2 of 465.65 +/- 28.63 ppm, CO of
      3.35 +/- 2.04 ppm, and VOCs of 1850.67 +/- 402 ppm. An air quality index
      indicated that ambient air quality for SO2 was very poor, NO2 ranged from
      moderate to very poor, whereas CO rating was moderate. Significant positive
      correlations existed between temperature and NO2, CO2, and CO and between
      humidity and VOCs. Significant relationships were also recorded between CO2 and
      NO2 and between CO and CO2. Poor urban planning, inadequate pollution control
      measure, and weak capacity to monitor air quality have implications for energy
      usage, air quality, and local meteorological parameters, with subsequent feedback
      into global climate change. Implementation of programs to monitor and control
      emissions in order to reduce air pollution will provide health, economic, and
      environmental benefits to the city. IMPLICATIONS: The need to develop and
      implement emission control programs to reduce air pollution in Dire Dawa City is
      urgent. This will provide enormous economic, health, and environmental benefits.
      It is expected that economic effects of air quality improvement will offset the
      expenditures for pollution control. Also, strategies that focus on air quality
      and climate change present a unique opportunity to engage different stakeholders
      in providing inclusive and sustainable development agenda for Dire Dawa.

PMID- 29215960
TI  - Graspable Objects Grab Attention More Than Images Do.
AB  - The opportunity an object presents for action is known as an affordance. A basic
      assumption in previous research was that images of objects, which do not afford
      physical action, elicit effects on attention and behavior comparable with those
      of real-world tangible objects. Using a flanker task, we compared interference
      effects between real graspable objects and matched 2-D or 3-D images of the
      items. Compared with both 2-D and 3-D images, real objects yielded slower
      response times overall and elicited greater flanker interference effects. When
      the real objects were positioned out of reach or behind a transparent barrier,
      the pattern of response times and interference effects was comparable with that
      for 2-D images. Graspable objects exert a more powerful influence on attention
      and manual responses than images because of the affordances they offer for manual
      interaction. These results raise questions about whether images are suitable
      proxies for real objects in psychological research.

PMID- 29215962
TI  - Personal exposure to fine particulate matter concentrations in central business
      district of a tropical coastal city.
AB  - : In the present study, personal exposure to fine particulate matter (particulate
      matter with an aerodynamic diameter <2.5 MUm [PM2.5]) concentrations in an urban
      hotspot (central business district [CBD]) was investigated. The PM monitoring
      campaigns were carried out at an urban hotspot from June to October 2015. The
      personal exposure monitoring was performed during three different time periods,
      i.e., morning (8 a.m.-9 a.m.), afternoon (12.30 p.m.-1.30 p.m.), and evening (4
      p.m.-5 p.m.), to cover both the peak and lean hour activities of the CBD. The
      median PM2.5 concentrations were 38.1, 34.9, and 40.4 ug/m3 during the morning,
      afternoon, and evening hours on the weekends. During weekdays, the median PM2.5
      concentrations were 59.5, 29.6, and 36.6 ug/m3 in the morning, afternoon, and
      evening hours, respectively. It was observed that the combined effect of traffic
      emissions, complex land use, and micrometeorological conditions created localized
      air pollution hotspots. Furthermore, the total PM2.5 lung dose levels for an
      exposure duration of 1 hr were 8.7 +/- 5.7 and 12.3 +/- 5.2 ug at CBD during
      weekends and weekdays, respectively, as compared with 2.5 +/- 0.8 ug at the urban
      background (UB). This study emphasizes the need for mobile measurement for short
      term personal exposure assessment complementing the fixed air quality monitoring.
      IMPLICATIONS: Personal exposure monitoring at an urban hotspot indicated space
      and time variation in PM concentrations that is not captured by the fixed air
      quality monitoring networks. The short-term exposure to higher concentrations can
      have a significant impact on health that need to be considered for the health
      risk-based air quality management. The study emphasizes the need of hotspot-based
      monitoring complementing the already existing fixed air quality monitoring in
      urban areas. The personal exposure patterns at hotspots can provide additional
      insight into sustainable urban planning.

PMID- 29215963
TI  - Utility of a unilateral accelerometer for monitoring upper extremity use in
      subacute stroke patients after discharge from hospital.
AB  - This study was to investigate the utility of a unilateral accelerometer, which is
      commonly used for monitoring upper extremity performance, in subacute stroke
      patients by comparing its use with other upper extremity assessments. Twenty-four
      participants were recruited and required to wear an accelerometer on the affected
      wrist for 3 hours daily for the first 4 weeks after discharge from hospital.
      Assessments included Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Action
      Research Arm Test (ARAT), Box and Block Test (BBT), and self-reporting Motor
      Activity Log (MAL). Assessments were made at 0, 4, 8, and 12 weeks after hospital
      discharge. How long the device was worn, movement amount, and movement percentage
      were extracted from the accelerometer. Throughout the 12-week observation,
      significant improvements in the participants were shown by the FMA-UE, ARAT, and
      BBT (p < 0.001, p = 0.026, and p < 0.001, respectively), but no significant
      change could be found using MAL or the accelerometer parameters across time (p =
      0.068 to 0.999). There was moderate-to-good correlation among the assessments;
      however, no significant correlation was obtained between any of the assessments
      and the accelerometer data. We suggest that the unilateral accelerometer might
      not be useful to reflect actual arm functions in daily activities.

PMID- 29215964
TI  - Real-world fuel use and gaseous emission rates for flex fuel vehicles operated on
      E85 versus gasoline.
AB  - : Flex fuel vehicles (FFVs) typically operate on gasoline or E85, an 85%/15%
      volume blend of ethanol and gasoline. Differences in FFV fuel use and tailpipe
      emission rates are quantified for E85 versus gasoline based on real-world
      measurements of five FFVs with a portable emissions measurement system (PEMS),
      supplemented chassis dynamometer data, and estimates from the Motor Vehicle
      Emission Simulator (MOVES) model. Because of inter-vehicle variability, an
      individual FFV may have higher nitrogen oxide (NOx) or carbon monoxide (CO)
      emission rates on E85 versus gasoline, even though average rates are lower. Based
      on PEMS data, the comparison of tailpipe emission rates for E85 versus gasoline
      is sensitive to vehicle-specific power (VSP). For example, although CO emission
      rates are lower for all VSP modes, they are proportionally lowest at higher VSP.
      Driving cycles with high power demand are more advantageous with respect to CO
      emissions, but less advantageous for NOx. Chassis dynamometer data are available
      for 121 FFVs at 50,000 useful life miles. Based on the dynamometer data, the
      average difference in tailpipe emissions for E85 versus gasoline is -23% for NOx,
      -30% for CO, and no significant difference for hydrocarbons (HC). To account for
      both the fuel cycle and tailpipe emissions from the vehicle, a life cycle
      inventory was conducted. Although tailpipe NOx emissions are lower for E85 versus
      gasoline for FFVs and thus benefit areas where the vehicles operate, the life
      cycle NOx emissions are higher because the NOx emissions generated during fuel
      production are higher. The fuel production emissions take place typically in
      rural areas. Although there are not significant differences in the total HC
      emissions, there are differences in HC speciation. The net effect of lower
      tailpipe NOx emissions and differences in HC speciation on ozone formation should
      be further evaluated. IMPLICATIONS: Reported comparisons of flex fuel vehicle
      (FFV) tailpipe emission rates for E85 versus gasoline have been inconsistent. To
      date, this is the most comprehensive evaluation of available and new data. The
      large range of inter-vehicle variability illustrates why prior studies based on
      small sample sizes led to apparently contradictory findings. E85 leads to
      significant reductions in tailpipe nitrogen oxide (NOx) and carbon monoxide (CO)
      emission rates compared with gasoline, indicating a potential benefit for ozone
      air quality management in NOx-limited areas. The comparison of FFV tailpipe
      emissions between E85 and gasoline is sensitive to power demand and driving
      cycles.

PMID- 29215965
TI  - Nitrogen oxide emission calculation for post-Panamax container ships by using
      engine operation power probability as weighting factor: A slow-steaming case.
AB  - : In this study, the nitrogen oxide (NOx) emission factors and total NOx
      emissions of two groups of post-Panamax container ships operating on a long-term
      slow-steaming basis along Euro-Asian routes were calculated using both the
      probability density function of engine power levels and the NOx emission
      function. The main engines of the five sister ships in Group I satisfied the Tier
      I emission limit stipulated in MARPOL (International Convention for the
      Prevention of Pollution from Ships) Annex VI, and those in Group II satisfied the
      Tier II limit. The calculated NOx emission factors of the Group I and Group II
      ships were 14.73 and 17.85 g/kWhr, respectively. The total NOx emissions of the
      Group II ships were determined to be 4.4% greater than those of the Group I
      ships. When the Tier II certification value was used to calculate the average
      total NOx emissions of Group II engines, the result was lower than the actual
      value by 21.9%. Although fuel consumption and carbon dioxide (CO2) emissions were
      increased by 1.76% because of slow steaming, the NOx emissions were markedly
      reduced by 17.2%. The proposed method is more effective and accurate than the NOx
      Technical Code 2008. Furthermore, it can be more appropriately applied to
      determine the NOx emissions of international shipping inventory. IMPLICATIONS:
      The usage of operating power probability density function of diesel engines as
      the weighting factor and the NOx emission function obtained from test bed for
      calculating NOx emissions is more accurate and practical. The proposed method is
      suitable for all types and purposes of diesel engines, irrespective of their
      operating power level. The method can be used to effectively determine the NOx
      emissions of international shipping and inventory applications and should be
      considered in determining the carbon tax to be imposed in the future.

PMID- 29215966
TI  - Effect of potassium hydroxide activation in the desulfurization process of
      activated carbon prepared by sewage sludge and corn straw.
AB  - : Series sludge straw-based activated carbons were prepared by sewage sludge and
      corn straw with potassium hydroxide (KOH) activation, and the desulfurization
      performance of activated carbons was studied. To obtain the best desulfurization
      performance, the optimum ratio between the raw materials and the activator was
      investigated. The results showed that when the mass ratio of sewage sludge, corn
      straw, and KOH was 3:7:2, the activated carbon obtained the best breakthrough and
      saturation sulfur sorption capacities, which were 12.38 and 5.74 times,
      respectively, those of samples prepared by the nonactivated raw materials. The
      appropriate KOH could improve the microporosity and alkaline groups, meanwhile
      reducing the lactone groups, which were all beneficial to desulfurization
      performance. The chemical adsorption process of desulfurization can be simplified
      to four main steps, and the main desulfurization products are elemental sulfur
      and sulfate. IMPLICATIONS: Sewage sludge (SS) and corn straw (CS) both have great
      production and wide distribution and are readily available in China. Much
      attention has been paid on how to deal with them effectively. Based on the
      environment protection idea of waste treatment with waste and resource recycling,
      low-cost adsorbents were prepared by these processes. The proposed method can be
      expanded to the municipal solid waste recycling programs and renewable energy
      plan. Thus, proceeding with the study of preparing activated carbon by SS and
      straw as a carbon-based dry desulfurization agent could obtain huge social,
      economic, and environmental benefits.

PMID- 29215967
TI  - Ambient fine particulate matter in China: Its negative impacts and possible
      countermeasures.
AB  - : In recent decades, China has experienced rapid economic development accompanied
      by increasing concentrations of ambient PM2.5, particulate matter of less than
      2.5 MUm in diameter. PM2.5 is now believed to be a carcinogen, causing higher
      lung cancer risks and generating losses to the economy and society. This meta
      analysis evaluates the losses generated by ambient PM2.5 in Suzhou from 2014 to
      2016 and predicts losses at different concentrations. Estimations of total losses
      in Beijing, Shanghai, Hangzhou, Guangzhou, Dalian, and Xiamen are also presented,
      with a total national loss in 2015. The authors then demonstrate that lowering
      ambient PM2.5 concentrations would be a realistic way for China to reduce the
      evaluated social losses in the short term. Possible legal measures are listed for
      lowering ambient PM2.5 concentrations. IMPLICATIONS: The present findings
      quantify the economic effects of ambient PM2.5 due to the increased incidence
      rate and mortality rate of lung cancer. Lowering ambient PM2.5 concentrations
      would be the most realistic way for China to reduce tghe evaluated social losses
      in the short term. Possible legal measures for lowering ambient PM2.5
      concentrations to reduce the total losses are identified.

PMID- 29215968
TI  - Food flows in the United Kingdom: The potential of surplus food redistribution to
      reduce waste.
AB  - : The increasing amount of food waste generated as a direct consequence of its
      excessive production, mismanagement, and wasteful behaviors represents a real
      challenge in promoting resource efficiency. In the United Kingdom (UK), the lack
      of robust mass flow data hinders the ability both to understand and address food
      waste challenges and to devise long-term sustainable prevention strategies. In
      recognition of these challenges, this paper seeks to (i) provide insights into
      the UK's annual estimates of food mass flows, including imports, exports,
      distribution, consumption, surplus food production, and final disposal; and (ii)
      scrutinize the uptake and redistribution of surplus food as a potential food
      waste prevention strategy. Evidence collected from several enterprises and
      community-led initiatives in the UK, and London specifically, supports that there
      is an increasing potential of making a shift towards food redistribution and
      reuse. Further analysis has shown that the outreach of food redistribution
      initiatives in the UK is currently limited, possibly because redistribution
      efforts remain largely fragmented and independent from each other. It is
      concluded that a national commitment could be instrumental in encouraging the
      roll-out of this practice, and governmental support through fiscal incentives
      could lead to the development of a larger and coherent surplus food
      redistribution system, ultimately enabling food waste prevention and recovery of
      food's multidimensional value. IMPLICATIONS: This paper deals with the topical
      issue of the increasing amount of food waste generated as a direct consequence of
      excessive production, mismanagement, and wasteful behavior, representing a real
      challenge in achieving sustainability and resource efficiency. Currently, only a
      small fraction of food is redistributed back into the system. Yet, a considerable
      fraction of food waste generated is edible; thus, better planning, storage, and
      coordination amongst the different stakeholders in the food supply chain is
      required in order to prevent its wastage and promote its reuse in accordance with
      the waste hierarchy.

PMID- 29215969
TI  - Protection from wintertime rainfall reduces nutrient losses and greenhouse gas
      emissions during the decomposition of poultry and horse manure-based amendments.
AB  - : Manure-based soil amendments (herein "amendments") are important fertility
      sources, but differences among amendment types and management can significantly
      affect their nutrient value and environmental impacts. A 6-month in situ
      decomposition experiment was conducted to determine how protection from
      wintertime rainfall affected nutrient losses and greenhouse gas (GHG) emissions
      in poultry (broiler chicken and turkey) and horse amendments. Changes in total
      nutrient concentration were measured every 3 months, changes in ammonium (NH4+)
      and nitrate (NO3-) concentrations every month, and GHG emissions of carbon
      dioxide (CO2), methane (CH4), and nitrous oxide (N2O) every 7-14 days. Poultry
      amendments maintained higher nutrient concentrations (except for K), higher
      emissions of CO2 and N2O, and lower CH4 emissions than horse amendments. Exposing
      amendments to rainfall increased total N and NH4+ losses in poultry amendments, P
      losses in turkey and horse amendments, and K losses and cumulative N2O emissions
      for all amendments. However, it did not affect CO2 or CH4 emissions. Overall,
      rainfall exposure would decrease total N inputs by 37% (horse), 59% (broiler
      chicken), or 74% (turkey) for a given application rate (wet weight basis) after 6
      months of decomposition, with similar losses for NH4+ (69-96%), P (41-73%), and K
      (91-97%). This study confirms the benefits of facilities protected from rainfall
      to reduce nutrient losses and GHG emissions during amendment decomposition.
      IMPLICATIONS: The impact of rainfall protection on nutrient losses and GHG
      emissions was monitored during the decomposition of broiler chicken, turkey, and
      horse manure-based soil amendments. Amendments exposed to rainfall had large
      ammonium and potassium losses, resulting in a 37-74% decrease in N inputs when
      compared with amendments protected from rainfall. Nitrous oxide emissions were
      also higher with rainfall exposure, although it had no effect on carbon dioxide
      and methane emissions. Overall, this work highlights the benefits of rainfall
      protection during amendment decomposition to reduce nutrient losses and GHG
      emissions.

PMID- 29215970
TI  - Energy expenditure in professional flat jockeys using doubly labelled water
      during the racing season: Implications for body weight management.
AB  - To formulate individualized dietary strategies for jockeys, it is vital that
      energy requirements are quantified. We measured total energy expenditure (TEE)
      over two separate weeks in spring and summer using doubly labelled water in a
      group of male flat jockeys (n = 8, 36.9 +/- 5.7 years, 164 +/- 8 cm, 54.6 +/- 2.5
      kg). Total energy intake (TEI) was self-recorded, as were all riding and
      structured exercise activity. Mean daily TEE was 10.83 (+/-2.3) and 10.66 (+/
      1.76) MJ, (p = .61) respectively. Self-reported TEI were 6.03 (+/-1.7) and 5.37
      (+/-1.1) MJ (p = .40), respectively, and were significantly lower than TEE (p =
      .01). Mean race rides were 17 (+/-6) and 13 (+/-3; p = 0.37) and horses ridden at
      morning exercise were 8 (+/-6) and 7 (+/-4; p = .77) respectively. Additional
      structured exercise was 76.25 (+/-95.1) and 52.5 (+/-80.9) min per week (p =
      .35), respectively. At the individual level, TEE was related to body mass and the
      level of non-racing physical activity, but not riding. Physical activity levels
      for TEE were 1.76 (+/-0.37) and 1.69 (+/-0.27; p = .59) and appear modest when
      compared with other athletes, and similar to age-matched non-athletes, suggesting
      that conventional sport-specific nutritional recommendations do not appear
      applicable. The large discrepancy between TEE and TEI suggests significant under
      reporting of dietary intake. These data now provide an appropriate framework from
      which to formulate jockey nutritional guidelines to promote the ability to
      achieve the daily weight target and improve athlete welfare.

PMID- 29215971
TI  - A Mediterranean-style dietary intervention supplemented with fish oil improves
      diet quality and mental health in people with depression: A randomized controlled
      trial (HELFIMED).
AB  - OBJECTIVES: We investigated whether a Mediterranean-style diet (MedDiet)
      supplemented with fish oil can improve mental health in adults suffering
      depression. METHODS: Adults with self-reported depression were randomized to
      receive fortnightly food hampers and MedDiet cooking workshops for 3 months and
      fish oil supplements for 6 months, or attend social groups fortnightly for 3
      months. Assessments at baseline, 3 and 6 months included mental health, quality
      of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty
      acid analysis. RESULTS: n = 152 eligible adults aged 18-65 were recruited (n = 95
      completed 3-month and n = 85 completed 6-month assessments). At 3 months, the
      MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more
      vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P =
      0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and
      vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = -2.10, P =
      0.04) and red meat/chicken (t = -2.13, P = 0.04). The MedDiet group had greater
      reduction in depression (t = -2.24, P = 0.03) and improved mental health QoL
      scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were
      sustained at 6 months. Reduced depression was correlated with an increased
      MedDiet score (r = -0.298, P = 0.01), nuts (r = -0.264, P = 0.01), and vegetable
      diversity (r = -0.303, P = 0.01). Other mental health improvements had similar
      correlations, most notably for increased vegetable diversity and legumes. There
      were some correlations between increased omega-3, decreased omega-6 and improved
      mental health. DISCUSSION: This is one of the first randomized controlled trials
      to show that healthy dietary changes are achievable and, supplemented with fish
      oil, can improve mental health in people with depression.

PMID- 29215972
TI  - Accuracy of Smartphone-Based Pulse Oximetry Compared with Hospital-Grade Pulse
      Oximetry in Healthy Children.
AB  - BACKGROUND: Pulse oximetry, a ubiquitous, noninvasive method to monitor oxygen
      saturation (SpO2), requires larger, nonportable equipment. Smartphone pulse
      oximeter applications (apps) provide a portable, cost-effective option, but are
      untested in children. We hypothesize that smartphone pulse oximetry will not be
      inferior to standard pulse oximetry measured in healthy children. MATERIALS AND
      METHODS: Two main types of pulse oximetry apps, a camera-based app (CBA) that
      uses a phone camera flash and lens and a probe-based app (PBA) that uses an
      external plug-in probe, were compared with standard pulse oximetry measured in
      children ages 2-13 years without a respiratory complaint and a triage SpO2 >=97%
      seen in a pediatric Emergency Department. Two investigators obtained heart rate
      and SpO2 using each app. Inter-rater reliability was tested using interclass
      correlations (ICCs), and Bland-Altman method was used to compare app values to
      triage measurements. RESULTS: Eighty-one patients were enrolled. ICC for SpO2 for
      PBA and CBA were 0.73 and -0.24, respectively. The 95% limits of agreement
      between the PBA SpO2 and triage SpO2 were -2.8 to +2.5 compared with -4.1 to +3.5
      for the CBA SpO2 and triage SpO2. Mean differences between triage SpO2 and the
      PBA SpO2 (-0.17%) and triage SpO2 and CBA SpO2 (-0.33%) were not statistically
      significant. DISCUSSION AND CONCLUSIONS: Smartphone-based pulse oximetry is not
      inferior to standard pulse oximetry in pediatric patients without hypoxia.
      Reliability was superior for PBA compared with CBA, with more precise agreement
      for the PBA compared with the CBA. Future studies should test pulse oximetry apps
      in a hypoxic pediatric population.

PMID- 29215973
TI  - Dissipation of antimicrobial resistance genes in compost originating from cattle
      manure after direct oral administration or post-excretion fortification of
      antimicrobials.
AB  - Dissipation of antimicrobial resistance genes (ARG) during composting of cattle
      manure generated through fortification versus administration of antimicrobials in
      feed was compared. Manure was collected from cattle fed diets containing (kg-1)
      dry matter (DM): (1) 44 mg chlortetracycline (CTC), (2) a mixture of 44 mg each
      of chlortetracycline and sulfamethazine (CTCSMZ), (3) 11 mg tylosin (TYL) or (4)
      Control, no antimicrobials. Manures were composted for 30 d with a single mixing
      after 16 d to generate the second heating cycle. Quantitative PCR (qPCR) was used
      to measure 16S rDNA and tetracycline (tet), erythromycin (erm) and sulfamethazine
      (sul) genes. Temperature peaks ranged from 48 to 68 degrees C across treatments
      in the first composting cycle, but except for the control, did not exceed 55
      degrees C in the second cycle. Copy numbers of 16S rDNA decreased (P < 0.05)
      during composting, but were not altered by antimcrobials. Except tet(L), all ARG
      decreased by 0.1-1.6 log10 g DM-1 in the first cycle, but some genes (tet[B],
      tet[L], erm[F], erm[X]) increased (P < 0.05) by 1.0-3.1 log10 g DM-1 in the
      second. During composting, levels of tet(M) and tet(W) in CTC, erm(A), erm(B) and
      erm(X) in TYL, and sul(1) in CTCSMZ remained higher (P < 0.05) in fed than
      fortified treatments. The dissipation of ARG during composting of manure
      fortified with antimicrobials differs from manure generated by cattle that are
      administered antimicrobials in feed, and does not always align with the
      dissipation of antimicrobial residues.

PMID- 29215975
TI  - Early Results of States' Efforts to Support, Scale, and Sustain the National
      Diabetes Prevention Program.
AB  - The Centers for Disease Control and Prevention (CDC) developed a cooperative
      agreement with health departments in all 50 states and the District of Columbia
      to strengthen chronic disease prevention and management efforts through the
      implementation of evidence-based strategies, such as CDC's National Diabetes
      Prevention Program. The National Diabetes Prevention Program supports
      organizations to deliver the year-long lifestyle change program that has been
      proven to prevent or delay the onset of type 2 diabetes among those at high risk.
      This article describes activities, barriers, and facilitators reported by funded
      states during the first 3 years (2013-2015) of a 5-year funding cycle.

PMID- 29215974
TI  - Evaluating Cross-Cutting Approaches to Chronic Disease Prevention and Management:
      Developing a Comprehensive Evaluation.
AB  - We provide an overview of the comprehensive evaluation of State Public Health
      Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated
      Risk Factors and Promote School Health (State Public Health Actions). State
      Public Health Actions is a program funded by the Centers for Disease Control and
      Prevention to support the statewide implementation of cross-cutting approaches to
      promote health and prevent and control chronic diseases. The evaluation addresses
      the relevance, quality, and impact of the program by using 4 components: a
      national evaluation, performance measures, state evaluations, and evaluation
      technical assistance to states. Challenges of the evaluation included assessing
      the extent to which the program contributed to changes in the outcomes of
      interest and the variability in the states' capacity to conduct evaluations and
      track performance measures. Given the investment in implementing collaborative
      approaches at both the state and national level, achieving meaningful findings
      from the evaluation is critical.

PMID- 29215976
TI  - Supporting Obesity Prevention in Statewide Quality Rating and Improvement
      Systems: A Review of State Standards.
AB  - INTRODUCTION: A quality rating and improvement system (QRIS) is a fundamental
      component of most states' early care and education infrastructures. States can
      use a QRIS to set standards that define high-quality care and award child care
      providers with a quality rating designation based on how well they meet these
      standards. The objective of this review was to describe the extent to which
      states' QRIS standards include obesity prevention content. METHODS: We collected
      publicly available data on states' QRIS standards. We compared states' QRIS
      standards with 47 high-impact obesity prevention components in Caring for Our
      Children: National Health and Safety Performance Standards; Guidelines for Early
      Care and Education Programs, 3rd Edition, and 6 additional topics based on the
      Centers for Disease Control and Prevention's Spectrum of Opportunities for
      Obesity Prevention in the Early Care and Education Setting. RESULTS: Thirty-eight
      states operated a state-wide QRIS in early 2015. Of those, 27 states' QRIS
      included obesity prevention standards; 20 states had at least one QRIS standard
      that aligned with the high-impact obesity prevention components, and 21 states
      had at least one QRIS standard that aligned with at least one of the 6 additional
      topics. QRIS standards related to the physical activity high-impact obesity
      prevention components were the most common, followed by components for screen
      time, nutrition, and infant feeding. CONCLUSION: The high proportion of states
      operating a QRIS that included obesity prevention standards, combined with the
      widespread use of QRISs among states, suggests that a QRIS is a viable way to
      embed obesity prevention standards into state early care and education systems.

PMID- 29215977
TI  - Early Outcomes of State Public Health Actions' School Nutrition Strategies.
AB  - INTRODUCTION: Since 2013, the State Public Health Actions to Prevent and Control
      Diabetes, Heart Disease, Obesity and Associated Risk Factors and Promote School
      Health (State Public Health Actions) program has been implemented to support and
      reinforce healthy choices and healthy behaviors among the US population. The
      Centers for Disease Control and Prevention's Division of Population Health's
      School Health Branch has been a critical component, ensuring that state health
      departments support schools in adopting nutrition standards and creating a
      supportive nutrition environment. The objective of this article was to describe
      early outcomes of the school nutrition strategies of State Public Health Actions.
      METHODS: We examined the extent of progress for short-term performance measures
      and for school nutrition evaluation questions, using data secured from 51
      grantees through the performance measures database and state evaluation reports.
      RESULTS: During the first 4 years of the cooperative agreement, grantees
      demonstrated significant progress compared with year 2 for school nutrition
      performance measures. Collectively, grantees provided professional development
      and technical assistance to staff in 7,672 local education agencies and reached
      more than 29 million students. Success was also noted for several nutrition
      practices in schools. CONCLUSION: These early outcomes suggest that State Public
      Health Actions has had a positive impact on the nutrition environment of US
      schools. Systematically addressing areas for improvement could further expand the
      reach of these efforts during the remainder of the cooperative agreement.

PMID- 29215978
TI  - State Public Health Actions to Prevent and Control Diabetes, Heart Disease,
      Obesity and Associated Risk Factors, and Promote School Health.
AB  - The National Center for Chronic Disease Prevention and Health Promotion at the
      Centers for Disease Control and Prevention funds a program to boost progress in
      reducing the prevalence and incidence of multiple chronic diseases and their
      associated risk factors. This article describes the program, State Public Health
      Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated
      Risk Factors, and Promote School Health, and the program's action model, design,
      and administration and management structure. This program is based on 4 domains
      of public health action: 1) epidemiology and surveillance, 2) environmental
      approaches, 3) health care system interventions, and 4) community programs linked
      to clinical services. The 4 domains of public health action leverage data to
      inform action, support healthy choices and behaviors, strengthen delivery of
      clinical preventive services, and help Americans better manage their health.

PMID- 29215979
TI  - Overweight and Obesity in Local Media: An Analysis of Media Coverage in CDC
      Funded Communities.
AB  - We conducted a content analysis of newspaper and television news coverage in
      Centers for Disease Control and Prevention (CDC) grantee locations from June 2011
      through May 2013. After searching 2 databases for news stories related to
      overweight or obesity, we coded and analyzed stories for valence (how the
      author/reporter framed overweight and obesity control strategies), descriptors,
      causes and solutions, and populations mentioned. Of almost 3,000 stories
      analyzed, most had a neutral or positive valence, depicted overweight and obesity
      as epidemic, discussed individual causes and environmental solutions most
      frequently, and mentioned children most often. Earned media can be part of
      addressing overweight and obesity by emphasizing prevention and by emphasizing
      both environmental and individual causes and solutions.

PMID- 29216003
TI  - Computational miRNomics.
AB  - Editorial The term MicroRNA or its contraction miRNA currently appears in 21,215
      titles of abstracts, published between 1997 and now, available on Pubmed (2016-21
      22:12:59 EET). 4,108 of these were published in 2016 alone which signifies the
      importance of miRNA-related research. MicroRNAs can be detected experimentally
      using various techniques like directional cloning of endogenous small RNAs but
      they are time consuming [1]. Additionally, it is necessary for the miRNA and its
      mRNA target(s) to be co-expressed to infer a functional relationship which is
      difficult, if not impossible, to achieve [2]. Since experimental approaches are
      facing such difficulties, they have been complemented by computational approaches
      [3] thereby defining the field of computational miRNomics. Due to the rapid
      development in the discipline, it is important to assess the state-of-the-art. In
      this special issue, several areas of the field are investigated ranging from pre
      miRNA detection via machine learning to application of differential expression
      analysis in plants. First, Sacar Demirci et al. discuss an approach to virus pre
      miRNA detection using machine learning [4]. Such approaches are based on
      parameterization of miRNAs and Yousef et al. discuss how to select among such
      features [5]. A different computational perspective is provided by Kotipalli et
      al. who model the kinetics of miRNA genesis and targeting [6]. To fuel more
      refined future models for genesis and targeting, it is important to establish
      miRNA and target expression under varying conditions. Zhang et al. [7] and Kanke
      et al. [8] discuss two approaches to quantify miRNAs and other non-coding short
      RNAs. Diler et al., finally, discuss actual biological implications of
      differentially expressed miRNAs [9]. This special issue on computational
      miRNomics, thus, provides a trajectory from detection of pre-miRNAs to biological
      implications of differentially expressed miRNAs. Additional topics will be
      covered in the upcoming second volume of the special issue on computational
      miRNomics.

PMID- 29216008
TI  - Adherence to growth hormone therapy in children and its potential barriers.
AB  - BACKGROUND: One of the main concerns in chronic diseases such as growth hormone
      (GH) deficiency is adherence to the treatment, which significantly affects
      treatment outcomes. METHODS: This cross-sectional study was conducted among 169
      GH recipient children (2-12 years) and teens (13-19 years) referred to a GH
      distributing teaching pharmacy. The eight-item Morisky Medication Adherence Scale
      (MMAS) and auto-compliance method were used for the assessment of patients'
      adherence to GH. The potential barriers to GH therapy adherence and medication
      persistence were also explored. RESULTS: Based on the MMAS method, 56.7% of the
      children and 57.9% of the adolescent groups were adherent to GH therapy.
      Conversely, according to the auto-compliance method almost all the patients were
      adherent in the children (95.2%) and adolescent (95.5%) groups. Forgetting to
      take the injection or refill the prescription, being away from home, exhaustion
      from long-term injection, drug shortage and inaccessibility to the pharmacy were
      barriers found to be significantly associated with a low adherence in the
      children group. While in the adolescent group, forgetting to take the injection,
      painful injection, concern about long-term complications and exhaustion from long
      term injection revealed a significant association with low adherence. Persistence
      with GH therapy was reported in 75.3% and 67% of children and adolescent
      patients, respectively. CONCLUSIONS: The current study revealed that overall
      adherence of the study population is low. Considering the barriers with
      significant association with adherence, different strategies can be incorporated
      to enhance adherence to GH therapy, i.e. providing early patient and parent
      education and support, medication reminder systems and longer duration of GH
      prescriptions.

PMID- 29216009
TI  - The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no
      additional benefit compared to spontaneous conceptions in the prediction of
      pregnancy complications.
AB  - OBJECTIVES: The aim of this study was to determine if the levels of biochemical
      aneuploidy markers in in vitro fertilisation (IVF)/intracytoplasmic sperm
      injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to
      verify if biochemical markers could predict pregnancy outcome in IVF/ICSI
      gestations. METHODS: This was a prospective observational study performed in a
      group of 551 patients who underwent a combined first trimester prenatal screening
      (ultrasound scan and serum markers). All patients were divided into two groups
      according to the mode of conception: IVF/ICSI pregnancies (study group) and
      spontaneous conceptions (control group). The concentrations of first trimester
      biochemical markers were presented as multiples of median (MoM) and were compared
      between the study and control groups. Analysed pregnancy complications included:
      preterm delivery (PTD), small for gestational age (SGA), gestational hypertension
      (GH), preeclampsia (PE) and gestational diabetes (GDM). RESULTS: The analysis was
      performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with
      complete data regarding obstetric outcome. There were no significant differences
      in the concentrations of biochemical markers between the analysed groups.
      Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive
      than in normotensive patients, although the difference was not significant.
      Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed
      in 18 (9.8%) and 25 delivered preterm (13.6%). CONCLUSIONS: The trend for lower
      PAPP-A MoM was visible in all affected patients, although the results did not
      reach statistical significance. The first trimester biochemical markers in
      assisted reproduction technique (ART) pregnancies do not seem to have additional
      effect on predicting the risk of pregnancy complications.

PMID- 29216010
TI  - Calcitonin gene-related peptide (CGRP): role in peripheral nerve regeneration.
AB  - Calcitonin gene-related peptide (CGRP) is a neuropeptide that has an important
      anti-inflammatory role in the immune system. Research has shown that CGRP is an
      integral part in peripheral nerve regeneration by (1) suppressing tumor necrosis
      factor-alpha, (2) forming an initial nerve bridge by increasing fibroblast
      motility and extracellular matrix synthesis, (3) vascularizing the spinal cord
      injury site, and (4) inducing Schwann cell (SC) proliferation. In this treatise,
      the following hypotheses will be explored: (1) CGRP is induced by c-Jun to
      regulate SC dedifferentiation, (2) CGRP promotes the chemotaxic migration of SCs
      along the nerve bridge, and (3) CGRP induces myelinophagy by activating various
      signaling pathways, such as p38 mitogen-activated protein kinase and
      Raf/extracellular signal-regulated kinase. These processes provide a framework
      for understanding the role of CGRP in peripheral nerve regeneration, which may be
      important in developing better strategies for nerve repair and gaining further
      insight into demyelinating diseases.

PMID- 29216011
TI  - Understanding the molecular mechanism of improved proliferation and osteogenic
      potential of human mesenchymal stem cells grown on a polyelectrolyte complex
      derived from non-mulberry silk fibroin and chitosan.
AB  - The development of engineered bone tissue, as a promising alternative to
      conventional bone grafts, has so far not proven successful and still remains
      challenging. Thus, attempts have been made in the present study to synthesize
      polyelectrolyte complex (PEC) scaffolds by blending chitosan (CS) to silk fibroin
      (SF) derived from the non-mulberry silkworm (Antheraea pernyi) at three different
      pH values (5.0, 6.0, and 7.0), and to characterize them in terms of morphology,
      ultrastructure and mechanical properties with scanning electron microscopy (SEM),
      Fourier-transform infrared spectroscopy, x-ray diffraction and tensile strength
      analyses. The prepared PEC scaffolds showed a mean pore size of 130 MUm, as
      revealed by SEM analysis, and a comparatively higher compressive strength. The
      findings of in vitro cytocompatibility, in vivo biocompatibility and osteogenic
      marker (genes/proteins) analysis suggest that the PECs blended at pH 7.0 showed
      greater stability and enhanced growth and an osteogenic differentiation
      capability of human mesenchymal stem cells (MSCs). To aid our understanding of
      protein-polyion binding mechanisms, we employed a molecular docking and
      simulation study of SF macrodomains and CS oligomer using Schrodinger 14 and
      GROMACS (Groningen Machine for Chemical Simulations) software. The study involved
      analytical techniques for macromolecular solution characterization and
      theoretical simulations based on molecular dynamics. The computational studies
      confirmed the presence of an integral RGD sequence that played a vital role in
      superior cell-attachment, proliferation and osteogenic differentiation of MSCs
      grown on the developed SF-CS PEC scaffolds.

PMID- 29216012
TI  - Antibacterial activity and heavy metal removal efficiency of electrospun medium
      molecular weight chitosan/nylon-6 nanofibre membranes.
AB  - Chitosan/nylon-6 nanofibres with antibacterial activity properties were prepared
      by electrospinning a chitosan/nylon-6 solution (containing medium molecular
      weight chitosan). Nanofibres with diameters in the range of 139-190 nm were
      obtained. The yield of low concentration chitosan/nylon-6 nanofibres was higher
      than that of high concentration chitosan/nylon-6 nanofibres. The affinity of
      chitosan toward lead was studied using a Pb(NO3)2 solution containing Pb(II) ions
      as the heavy metal solution. The rejection of lead ions by the chitosan/nylon
      membranes was investigated under various chitosan concentrations. The optimum
      removal values for Pb(NO2)3 and NaCl were found to be 74% and 71%, respectively.
      The nanofibres developed in this study exhibited an excellent antibacterial
      activity (95%) against Escherichia coli.

PMID- 29216013
TI  - Bio-inspired synthesis of a hierarchical self-assembled zinc phosphate
      nanostructure in the presence of cowpea mosaic virus: in vitro cell cycle,
      proliferation and prospects for tissue regeneration.
AB  - Self-assembly is an important auto-organization process used in designing
      structural biomaterials which have the potential capability to heal tissues after
      traumatic injury. Although various materials having the ability to heal after
      injury are available, there is still a substantial need to develop new improved
      materials. To address this issue, we have developed hierarchical three
      dimensional (3D) self-assembled zinc phosphate (Zn3(PO4)2) in the presence of
      cowpea mosaic virus (CPMV). Zn3(PO4)2 nanoparticles are self-assembled into
      nanosheets with a high degree of isotropy and then self-organized into a 3D
      structure that can enhance surface interactions with biological entities. The
      self-assembled structure is formed through the auto-organization of nanoparticles
      of size ~50 nm under the influence of CPMV. The cellular response of self
      assembled Zn3(PO4)2 and cell-particle adhesion behavior have been investigated
      through in vitro studies using modeled osteoblast-like MG63 cells. Self-assembled
      Zn3(PO4)2 resulted in proliferation of MG63 cells of up to 310% within 7 days of
      incubation. A 15% higher proliferation was obtained than with commercially
      available hydroxyapatite (HAp). Immunofluorescent analysis of MG63 cells after co
      culturing with self-assembled Zn3(PO4)2 confirmed the healthy cytoskeletal
      organization and dense proliferation of MG63 cells. Further, Zn3(PO4)2 exhibited
      ~28% cell-cycle progression in S phase, which is higher than obtained with
      commercially available HAp. Overall, these results demonstrate the multiple
      functions of hierarchical self-assembled Zn3(PO4)2 in the regeneration of bone
      tissue without defects and increasing the formation of cellular networks, and
      suggest its use in bone tissue engineering.

PMID- 29216014
TI  - Incorporating patients' preference diagnosis in implantable cardioverter
      defibrillator decision-making: a review of recent literature.
AB  - PURPOSE OF REVIEW: Strong recommendations exist for implantable cardioverter
      defibrillators (ICD) in appropriately selected patients. Yet, patient preferences
      are not often incorporated when decisions about ICD therapy are made. Literature
      published since 2016 was reviewed aiming to discuss current advances and ongoing
      challenges with ICD decision-making in adults, discuss shared decision-making
      (SDM) as a strategy to incorporate preference diagnoses, summarize current
      evidence on effective interventions to facilitate SDM, and identify opportunities
      for research and practice. RECENT FINDINGS: Advances in risk stratification can
      identify patients who will most and least likely benefit from the ICD.
      Interventions to support SDM are emerging. These interventions present options,
      the risks, and the benefits of each option, and elicit patients' values and
      preferences regarding possible outcomes. SUMMARY: Appropriate patient selection
      for initial or continued ICD therapy is multifactorial. It requires accurate
      clinical diagnosis using careful risk stratification and accurate preference
      diagnosis based upon the patient's preferences. SDM aims to unite the elements
      that constitute these two equally important diagnoses. High-quality decision
      making will be difficult to achieve if patients lack or misunderstand
      information, and if evolving patient preferences are not incorporated when making
      decisions.

PMID- 29216015
TI  - Graft quality verification in coronary artery bypass graft surgery: how, when and
      why?

PMID- 29216016
TI  - Why the CANTOS Is a Game Changer in Cardiovascular Medicine.

PMID- 29216017
TI  - Sleep Quantity and Quality of Ontario Wildland Firefighters Across a Low-Hazard
      Fire Season.
AB  - OBJECTIVE: The aim of the study was to assess the sleep quality, quantity, and
      fatigue levels of Canadian wildland firefighters while on deployment. METHODS:
      Objective and subjective sleep and fatigue measures were collected using
      actigraphy and questionnaires during non-fire (Base) and fire (Initial Attack and
      Project) deployments. RESULTS: Suboptimal sleep quality and quantity were more
      frequently observed during high-intensity, Initial Attack fire deployments.
      Suboptimal sleep was also exhibited during non-fire (Base) work periods, which
      increases the risk of prefire deployment sleep debt. Self-reported, morning
      fatigue scores were low-to-moderate and highest for Initial Attack fire
      deployments. CONCLUSIONS: The study highlights the incidence of suboptimal sleep
      patterns in wildland firefighters during non-fire and fire suppression work
      periods. These results have implications for the health and safety practices of
      firefighters given the link between sleep and fatigue, in a characteristically
      hazardous occupation.

PMID- 29216018
TI  - Impact of a Graduated Approach on Opioid Initiation and Loss of Earnings
      Following Workplace Injury: A Time Series Analysis.
AB  - OBJECTIVE: The aim of this study was to explore the impact of the Ontario
      Workplace Safety and Insurance Board's (WSIB's) graduated approach to opioid
      management on opioid prescribing and disability claim duration. METHODS: We
      studied patterns of opioid use and disability claim duration among Ontarians who
      received benefits through the WSIB between 2002 and 2013. We used interventional
      time series analysis to assess the impact of the WSIB graduated formulary on
      these trends. RESULTS: After the introduction of the graduated formulary,
      initiation of short- and long-acting opioids fell significantly (P < 0.0001). We
      also observed a shift toward the use of short-acting opioids alone (P < 0.0001).
      Although disability claim duration declined, this could not be ascribed to the
      intervention (P = 0.18). CONCLUSION: A graduated opioid formulary may be an
      effective tool for providers to promote more appropriate opioid prescribing.

PMID- 29216019
TI  - Familial Association of Granulocyte-Macrophage Colony-Stimulating Factor
      Autoantibodies in Inflammatory Bowel Disease.
AB  - OBJECTIVES: Elevated granulocyte-macrophage colony-stimulating factor auto
      antibodies (GM-CSF Ab) are associated with increased intestinal permeability and
      stricturing behavior in Crohn disease (CD). We tested for familial association of
      serum GM-CSF Ab level in CD and ulcerative colitis (UC) families. METHODS: Serum
      GM-CSF Ab concentration was determined in 230 pediatric CD probands and 404 of
      their unaffected parents and siblings, and 45 UC probands and 71 of their
      unaffected parents and siblings. A linear mixed effects model was used to test
      for familial association. The intra-class correlation coefficient (ICC) was used
      to determine the degree of association of the serum GM-CSF Ab level within
      families in comparison with the degree of association among families. RESULTS:
      The median (IQR) serum GM-CSF Ab concentration was higher in CD probands than in
      UC probands (1.5 [0.5,5.4] MUg/mL vs 0.7 [0.3, 1.6] MUg/mL, P = 0.0002). The
      frequency of elevated serum GM-CSF Ab concentration >=1.6 MUg/mL was increased in
      unaffected siblings of CD probands with elevated GM-CSF Ab, compared with
      unaffected siblings of CD probands without elevated GM-CSF Ab (33% vs 13%,
      respectively, P = 0.04). A similar result was observed within UC families. In
      families of CD patients, the mean (95th CI) ICC was equal to 0.153 (0.036,
      0.275), P = 0.001, whereas in families of UC patients, the mean (95th CI) ICC was
      equal to 0.27 (0.24, 0.31), P = 0.047. CONCLUSIONS: These data confirmed familial
      association of serum GM-CSF Ab levels. This could be accounted for by either
      genetic or environmental factors shared within the family.

PMID- 29216020
TI  - Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A
      Randomized Controlled Noninferiority Trial.
AB  - OBJECTIVE: A high protein content of nonhydrolyzed infant formula exceeding
      metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed
      formula with too low protein (LP) content may result in inadequate growth. The
      aim of this study was to investigate noninferiority of partial and extensively
      hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than
      conventionally, regularly used formulas, with or without synbiotics for normal
      growth of healthy term infants. METHODS: In an European multi-center, parallel,
      prospective, controlled, double-blind trial, 402 formula-fed infants were
      randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF
      with or without synbiotics, LP-eHF formula with synbiotics, or regular protein
      eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as
      observational reference group. As primary endpoint, noninferiority of daily
      weight gain during the first 4 months of life was investigated comparing the LP
      group to a regular protein eHF group. RESULTS: A comparison of daily weight gain
      in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving
      regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per
      protocol [PP] population). Noninferiority was also confirmed for the other tested
      LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid
      concentrations demonstrated a safe and balanced nutritional composition.
      Energetic efficiency for growth (weight) was slightly higher in LPeHF and
      synbiotics compared with LPpHF and synbiotics. CONCLUSIONS: All tested hydrolyzed
      LP formulas allowed normal weight gain without being inferior to regular protein
      eHF in the first 4 months of life. This trial was registered at
      clinicaltrials.gov, NCT01143233.

PMID- 29216021
TI  - Long-term Results and Quality of Life Assessment in Biliary Atresia Patients: A
      35-Year Experience in a Tertiary Hospital.
AB  - OBJECTIVES: To review long-term transplant-free survival and quality of life
      (QOL) of patients with biliary atresia (BA). METHODS: A retrospective study
      reviewing all patients with Kasai operation between January 1, 1980 and December
      31, 2015 was performed to evaluate the transplant-free survival. Subgroup
      analysis of patients older than 20 years was carried out to assess the QOL using
      the Short Form-36 Health Survey and incidences of disease-related complications.
      Comparison between patients with native and transplanted liver was performed
      using two-tailed independent samples t-test (P value < 0.05, significant).
      RESULTS: The 20-year Kaplan-Meier transplant-free survival of the 141 patients in
      our study was 51%. The subgroup analysis of long-term survivors revealed a trend
      of increased prevalence of complications like esophageal varices, portal
      hypertension, and recurrent admissions in the patient groups with raised serum
      bilirubin (SB).Thirty-one patients were successfully contacted for QOL
      assessment, 26 (16 with native liver and 10 with transplanted liver) responded
      (76.5%). BA patients who were documented to have active complications have a
      significantly lower vitality score (50.7 vs 57.5, P = 0.015). There was no
      statistically significant difference in the scores between the transplanted group
      and the disease-free control group. However, the native liver group achieved a
      lower score in both the general health section (42.9 vs 49.6, P = 0.029) and the
      overall physical component (49.6 vs 54.4, P = 0.037). CONCLUSIONS: A significant
      proportion of our patients survive with their native liver for more than 20
      years. These long-term survivors may suffer from complications that impair their
      QOL. They require continuous life-long care.

PMID- 29216022
TI  - Yield of Endoscopic Ultrasound in Children and Adolescent With Acute Recurrent
      Pancreatitis.
AB  - OBJECTIVES: Endoscopic ultrasound (EUS) is an established tool for evaluation of
      adults with acute recurrent pancreatitis (ARP) whereas data in pediatrics is
      limited. Our study assessed the role of EUS in identifying etiology including
      changes of chronic pancreatitis (CP) in children and adolescents with ARP.
      METHODS: Children with ARP (>=2 episodes of acute pancreatitis [AP]) were
      prospectively evaluated with a detailed clinical proforma and EUS. Subjects with
      known etiology of ARP or CP on ultrasonography/computed tomography and magnetic
      resonance cholangiopancreatography (MRCP, Cambridge grade >=3) were excluded.
      Parenchymal and ductal changes on EUS as per minimal standards terminology (MST)
      features were noted. RESULTS: Thirty-two children (22 boys, age 14 [8-18] years)
      with ARP (median of 3 [2-5] episodes of AP) were enrolled. EUS was safe and
      technically successful in all. Gall bladder sludge was found in 1 (3%) case and
      none had other pancreatobiliary structural abnormalities. EUS diagnosis of CP
      (>=4 features) was made in 10/32 (31%) cases. Subjects with CP on EUS had a
      longer disease duration than those without CP (45 [10-97] vs 22 [8-78] months; P
      = ns). MRCP was normal in 28 and showed pancreas divisum in 1 case. Three cases
      had equivocal (Cambridge II) changes at initial MRCP and 2 of them had repeat
      MRCP, which showed definite (Cambridge IV) CP. All these 3 cases had CP on EUS.
      CONCLUSIONS: EUS diagnosed CP (>=4 features) in 31% and biliary abnormality in 3%
      children with ARP. EUS is safe, sensitive, and useful for early diagnosis of CP
      in children with ARP.

PMID- 29216023
TI  - Corticosteroids for Preventing Caustic Esophageal Strictures: Systematic Review
      and Meta-analysis.
AB  - OBJECTIVES: Caustic ingestion can have a complicated clinical course.
      Corticosteroids are widely used but there is uncertainty about its role in
      preventing esophageal stricture formation following caustic ingestion. This
      systematic review and meta-analysis assessed the available clinical evidence
      regarding the efficacy and safety of corticosteroids for preventing esophageal
      strictures following caustic injury. METHODS: We assessed randomized controlled
      trials (RCTs) that compared corticosteroids versus no corticosteroids in the
      prevention of esophageal stricture formation following caustic ingestion. We
      searched the following databases from inception to March 2017: PubMed, Embase,
      and the Cochrane Central Register of Controlled Trials. Two reviewers retrieved
      eligible articles, assessed risk of bias, and performed data extraction. The main
      outcome measure was the prevention of esophageal stricture formation. RESULTS:
      The search identified 763 citations. Three RCTs involving 244 participants met
      the inclusion criteria. There was no benefit of corticosteroids in the prevention
      of esophageal strictures following the ingestion of caustic materials (risk ratio
      [RR] = 0.63, 95% CI = 0.29-1.37). CONCLUSIONS: The available evidence does not
      support the use of corticosteroids for the prevention of esophageal strictures
      following caustic ingestion. The overall quality of the evidence is limited
      because of methodological weaknesses and small sample sizes in the primary
      studies.

PMID- 29216025
TI  - Erratum: Vol. 66, No. 47.

PMID- 29216026
TI  - QuickStats: Percentage of Children Aged 4-17 Years Who Had Ever Had Varicella
      (Chickenpox),* by Age Group - National Health Interview Survey, 2007-2016?.
AB  - During 2007-2016, the percentage of children aged 4-17 years who had ever had
      chickenpox decreased among both younger children (aged 4-11 years) and older
      children (aged 12-17 years). Among younger children, the percentage of children
      who had ever had chickenpox declined by 73.9%, from 16.1% in 2007 to 4.2% in
      2016. Among older children the percentage who had ever had chickenpox declined by
      76.9%, from 61.4% in 2007 to 14.2% in 2016. During 2007-2016, older children were
      more likely than younger children to have ever had chickenpox.

PMID- 29216024
TI  - Maxillary Cortical Bone Thickness in a South-Eastern Anatolian Population: A Cone
      Beam Computed Tomography Study.
AB  - BACKGROUND The aim of this study was to measure the distance between the
      maxillary premolar and molar teeth apices to the buccal cortical bone and
      evaluate differences in gender and age group, using cone beam computed tomography
      (CBCT). MATERIAL AND METHODS This retrospective study comprised of 451 premolar
      and molar teeth of one hundred and thirteen patients who were admitted to Dicle
      University, Faculty of Dentistry, Department of Dentomaxillofacial Radiology for
      different reasons. Data were analyzed using Student's t-tests and Tukey HSD
      tests. RESULTS There was significant difference in buccal bone thickness by
      gender (p<0.05). The thinnest point of the maxillary buccal bone was measured in
      women as 2.11 mm and in men as 2.02 mm in the first premolar teeth. The thickest
      point of maxillary buccal bone was measured in women as 9.87 mm and in men 10.71
      mm palatinal root of the first molar. A comparison of buccal bone thickness
      between age showed a statistically significant difference at the distobuccal and
      palatinal roots of the first molar, at the mesiobuccal root of the second molar
      (p<0.05). CONCLUSIONS The measurements of maxillar buccal bone thickness using
      CBCT for various dental procedures especially in endodontic surgery, orthodontic
      mini implant treatment, dental implant procedures, and healing after tooth
      extraction that are important knowledge.

PMID- 29216027
TI  - Acute Malnutrition Among Children, Mortality, and Humanitarian Interventions in
      Conflict-Affected Regions - Nigeria, October 2016-March 2017.
AB  - A public health emergency was declared by the Nigerian Federal Ministry of Health
      in northeastern Nigeria in June 2016 and escalated by the United Nations to a
      Level 3 Emergency in August 2016, after confirmation of wild poliovirus and
      measles outbreaks and evidence that prevalence of acute malnutrition exceeded
      emergency thresholds in areas newly liberated from Boko Haram control (1,2). To
      monitor rates of mortality, acute malnutrition among children, infectious disease
      morbidity, and humanitarian interventions after the emergency declaration, a
      series of cross-sectional household surveys were conducted in fall 2016 and
      winter 2017 in the northeastern states of Borno and Yobe using a cluster
      methodology. All-cause mortality among all age groups (crude mortality) and among
      children aged <5 years (under-five mortality) were above emergency thresholds in
      2017 and significantly increased from 2016, despite evidence of increased
      preventive public health interventions, including measles vaccination. Access to
      treatment for common childhood illnesses remained very low, as evidenced by
      reports of fewer than one in six children in areas outside Borno's capital
      receiving any care for diarrhea. The data from these surveys provide evidence of
      excessively high mortality (particularly among children), highlight the impact of
      ongoing violence, and underscore the need for humanitarian efforts to scale up
      access to treatment services in conflict-affected areas.

PMID- 29216028
TI  - Progress Toward Global Eradication of Dracunculiasis, January 2016-June 2017.
AB  - Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a
      parasitic worm. Approximately 1 year after a person acquires infection from
      contaminated drinking water, the worm emerges through the skin, usually on a
      lower limb (1). Pain and secondary bacterial infection can cause temporary or
      permanent disability that disrupts work and schooling. The campaign to eradicate
      dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly
      called for dracunculiasis elimination,* and the global Guinea Worm Eradication
      Program, led by the Carter Center and supported by the World Health Organization
      (WHO), United Nations Children's Fund, CDC, and other partners, began assisting
      ministries of health in countries with endemic dracunculiasis. In 1986, an
      estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia
      (2). Since then, although the goal of eradicating dracunculiasis has not been
      achieved, considerable progress has been made. Compared with the 1986 estimate,
      the annual number of reported cases in 2016 has declined by >99%, and cases are
      confined to three countries with endemic disease. This report updates published
      (3-4) and unpublished surveillance data reported by ministries of health and
      describes progress toward dracunculiasis eradication during January 2016-June
      2017. In 2016, a total of 25 cases were reported from three countries (Chad [16],
      South Sudan [six], Ethiopia [three]), compared with 22 cases reported from the
      same three countries and Mali in 2015 (Table 1). The 14% increase in cases from
      2015 to 2016 was offset by the 25% reduction in number of countries with
      indigenous cases. During the first 6 months of 2017, the overall number of cases
      declined to eight, all in Chad, from 10 cases in three countries (Chad [four],
      South Sudan [four] and Ethiopia [two]) during the same period of 2016. Continued
      active surveillance, aggressive detection, and appropriate management of cases
      are essential eradication program components; however, epidemiologic challenges,
      civil unrest, and insecurity pose potential barriers to eradication.

PMID- 29216029
TI  - Disparities in Hospital-Reported Breast Milk Use in Neonatal Intensive Care Units
      - United States, 2015.
AB  - Breast milk is the recommended nutrition for infants. For preterm infants, when
      mother's milk is not available, pasteurized donor milk is recommended (1). Non
      Hispanic black mothers are at increased risk for having a preterm birth and for
      not breastfeeding (2,3); however, it is not known whether demographic disparities
      exist in the use of breast milk in neonatal intensive care units (NICUs). Data
      from CDC's 2015 Maternity Practices in Infant Nutrition and Care (mPINC) survey,
      which does not collect patient-level demographics, were linked to the 2011-2015
      U.S. Census Bureau's American Community Survey (ACS)* to examine use of breast
      milk in NICUs based on demographic makeup of the hospital's postal code area.
      Among U.S. hospitals with a NICU, the use of mother's own milk and donor milk
      were examined by the percentage of non-Hispanic black (black) residents in the
      hospital postal code area, categorized as being above or below the national
      average (12.3%). In postal codes with >12.3% black residents, 48.9% of hospitals
      reported using mothers' own milk in >=75% of infants in the NICU, and 38.0%
      reported not using donor milk, compared with 63.8% and 29.6% of hospitals,
      respectively, in postal codes with <=12.3% black residents. Further investigation
      is needed to understand variations in breast milk use in NICUs. Targeted efforts
      to increase breast milk use in hospitals located in postal codes where the
      percentage of black mothers is above the national average might help ensure more
      equitable access to breast milk for preterm and other high-risk infants.

PMID- 29216031
TI  - Early career investigator highlight-March.

PMID- 29216030
TI  - Update: Influenza Activity - United States, October 1-November 25, 2017.
AB  - Influenza activity in the United States was low during October 2017, but has been
      increasing since the beginning of November. Influenza A viruses have been most
      commonly identified, with influenza A(H3N2) viruses predominating. Several
      influenza activity indicators were higher than is typically seen for this time of
      year. The majority of influenza viruses characterized during this period were
      genetically or antigenically similar to the 2017-18 Northern Hemisphere cell
      grown vaccine reference viruses. These data indicate that currently circulating
      viruses have not undergone significant antigenic drift; however, circulating
      A(H3N2) viruses are antigenically less similar to egg-grown A(H3N2) viruses used
      for producing the majority of influenza vaccines in the United States. It is
      difficult to predict which influenza viruses will predominate in the 2017-18
      influenza season; however, in recent past seasons in which A(H3N2) viruses
      predominated, hospitalizations and deaths were more common, and the effectiveness
      of the vaccine was lower. Annual influenza vaccination is recommended for all
      persons aged >=6 months who do not have contraindications. Multiple influenza
      vaccines are approved and recommended for use during the 2017-18 season, and
      vaccination should continue to be offered as long as influenza viruses are
      circulating and unexpired vaccine is available. This report summarizes U.S.
      influenza activity* during October 1-November 25, 2017 (surveillance weeks 40
      47).?.

PMID- 29216032
TI  - Notable advances 2017.

PMID- 29216033
TI  - Fattening the role of Ca2+ cycling in adaptive thermogenesis.

PMID- 29216034
TI  - Timeline of events.

PMID- 29216035
TI  - Cutting out the liver fat.

PMID- 29216036
TI  - Drugs that made headlines in 2017.

PMID- 29216038
TI  - Correction.
AB  - This corrects the article DOI: 10.1038/nm1117-1244.

PMID- 29216037
TI  - Recognition of self-DNA drives cardiac inflammation: why broken hearts fail.

PMID- 29216039
TI  - Corrigendum: Persisting positron emission tomography lesion activity and
      Mycobacterium tuberculosis mRNA after tuberculosis cure.
AB  - This corrects the article DOI: 10.1038/nm.4177.

PMID- 29216040
TI  - Targeted cellular immunotherapy for T cell malignancies.

PMID- 29216041
TI  - Organoids lead the cancer attack.

PMID- 29216043
TI  - The Yearbook.

PMID- 29216042
TI  - The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter
      KCC2 but does potentiate GABAA receptor activity.

PMID- 29216044
TI  - Reply to The small molecule CLP257 does not modify activity of the K+-Cl- co
      transporter KCC2 but does potentiate GABAA receptor activity.

PMID- 29216045
TI  - Corrigendum: ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation
      and organ fibrosis.
AB  - This corrects the article DOI: 10.1038/nm.4419.

PMID- 29216046
TI  - Optical modeling of fiber organic photovoltaic structures using a transmission
      line method.
AB  - An optical model has been developed and evaluated for the calculation of the
      external quantum efficiency of cylindrical fiber photovoltaic structures. The
      model is based on the transmission line theory and has been applied on single and
      bulk heterojunction fiber-photovoltaic cells. Using this model, optimum design
      characteristics have been proposed for both configurations, and comparison with
      experimental results has been assessed.

PMID- 29216047
TI  - Improved progressive morphological filter for digital terrain model generation
      from airborne lidar data.
AB  - Obtaining high-precision filtering results from airborne lidar point clouds in
      complex environments has always been a hot topic. Mathematical morphology was
      widely used for filtering, owing to its simplicity and high efficiency. However,
      the morphology-based algorithms are deficient in preserving terrain details. In
      order to obtain a better filtering effect, this paper proposed an improved
      progressive morphological filter based on hierarchical radial basis function
      interpolation (PMHR) to refine the classical progressive morphological filter.
      PMHR involved two main improvements, namely, automatic setting of self-adaptive
      thresholds and terrain details preservation, respectively. The performance of
      PMHR was evaluated using datasets provided by the International Society for
      Photogrammetry and Remote Sensing. Experimental results show that PMHR achieved
      good performance under variant terrain features with an average total error of
      4.27% and average Kappa coefficient of 84.57%.

PMID- 29216048
TI  - Deformation of a prestressed liquid lens membrane.
AB  - This paper presents a complete model for analysis of the deformed shape of a
      prestressed circular axisymmetric membrane of a liquid lens. The governing
      equations are derived using the exact relation between displacements and the
      Green-Lagrange strains combined with the Saint Venant-Kirchhoff material law,
      which postulates a linear relation between the Green-Lagrange strains and the
      second Piola-Kirchoff stresses. A numerical solution based on minimization of
      potential energy is illustrated by an example, and the dependence of the maximum
      membrane deflection on material properties and initial prestress is analyzed. The
      theoretical model is then experimentally validated. It is shown that the model is
      suitable for large-strain analysis of liquid lens membranes and provides
      sufficiently accurate results that can be used in further analyses and
      simulations of imaging properties of active optical elements based on liquid
      lenses.

PMID- 29216049
TI  - Field-only integral equation method for time domain scattering of electromagnetic
      pulses.
AB  - The scattering of electromagnetic pulses is described using a non-singular
      boundary integral method to solve directly for the field components in the
      frequency domain, and Fourier transform is then used to obtain the complete space
      time behavior. This approach is stable for wavelengths both small and large
      relative to characteristic length scales. Amplitudes and phases of field values
      can be obtained accurately on or near material boundaries. Local field
      enhancement effects due to multiple scattering of interest to applications in
      microphotonics are demonstrated.

PMID- 29216050
TI  - Spatial intensity profiling of elastic and inelastic scattering in isotropic and
      anisotropic liquids by immersion of a spherical silicon photocell.
AB  - The transverse spatial intensity distribution of elastic and inelastic light
      scattering in passive and active as well as weak and strong scattering liquid
      media has been studied by using Sphelar One p-n junction silicon spherical
      photocells. We immersed a Sphelar One in these scattering solutions and measured
      the photoconductive response in reverse biased photodiode (PD) configuration. The
      passive weak scattering medium was pure ethanol (EtOH), whereas the passive
      strong scattering medium was 5CB nematic liquid crystal (NLC). Solutions of 0.1
      mM Rhodamine 640 perchlorate laser dye in EtOH and in 5CB NLC were used as active
      scattering media. The response of Sphelar One was strongly enhanced in 5CB NLC
      compared to EtOH, as well as in active solutions compared to passive solutions.
      The morphology of the Sphelar One is already advantageous over conventional one
      sided planar PDs inside liquid solutions. This omnidirectional response of the
      Sphelar One can further be enhanced by optimizing the properties of the
      surrounding passive elastic and active inelastic scatterers.

PMID- 29216051
TI  - Highly efficient waveguide display with space-variant volume holographic
      gratings.
AB  - We propose a highly efficient waveguide display based on space-variant volume
      holographic gratings (SVVHGs). The local period and slant angle of the SVVHG vary
      along the tangential direction, enabling variant incident angles to satisfy the
      Bragg condition of the local gratings. As a result, we enlarge the field of view
      (FOV) without using the conventional multiplexing scheme, while achieving high
      efficiency and large FOV at the same time. We experimentally record the SVVHGs on
      Bayfol HX200 films. We demonstrate that the proposed display can achieve 31.9%
      system efficiency for a broadband light source and 52.3% for a coherent light
      source, 20 degrees  FOV, and high brightness uniformity, making it a promising
      candidate for widespread applications in the augmented reality (AR) industry.

PMID- 29216052
TI  - Modified surface testing method for large convex aspheric surfaces based on
      diffraction optics.
AB  - Large convex aspheric optical elements have been widely applied in advanced
      optical systems, which have presented a challenging metrology problem.
      Conventional testing methods cannot satisfy the demand gradually with the change
      of definition of "large." A modified method is proposed in this paper, which
      utilizes a relatively small computer-generated hologram and an illumination lens
      with certain feasibility to measure the large convex aspherics. Two example
      systems are designed to demonstrate the applicability, and also, the sensitivity
      of this configuration is analyzed, which proves the accuracy of the configuration
      can be better than 6 nm with careful alignment and calibration of the
      illumination lens in advance. Design examples and analysis show that this
      configuration is applicable to measure the large convex aspheric surfaces.

PMID- 29216053
TI  - Low-loss reciprocal optical terminals for two-way time-frequency transfer.
AB  - We present the design and performance of a low-cost, reciprocal, compact free
      space terminal employing tip/tilt pointing compensation that enables optical two
      way time-frequency transfer over free-space links across the turbulent
      atmosphere. The insertion loss of the terminals is ~1.5  dB with total link
      losses of 15 dB, 24 dB, and 50 dB across horizontal, turbulent 2-km, 4-km, and 12
      km links, respectively. The effects of turbulence on pointing control and
      aperture size, and their influence on the terminal design, are discussed.

PMID- 29216054
TI  - Angular random walk limited by Rayleigh backscattering in resonator fiber optic
      gyros.
AB  - This paper is concerned with the angular random walk (ARW) limited by Rayleigh
      backscattering in the resonator fiber optic gyro (RFOG) with a light source of
      arbitrary temporal coherence. First, a model of Rayleigh backscattering noise in
      RFOGs is established to predict the fluctuation characteristics of backscattered
      intensity and interference intensity. Next, the formula for the ARW limited by
      Rayleigh backscattering is derived, and the requirement of carrier suppression
      level is calculated to make sure the ARW is limited by the detector's shot noise
      rather than Rayleigh scattering noise. Finally, the influences of the cavity
      length, the linewidth, and the finesse on the ARW limited by Rayleigh
      backscattering are investigated. The results predict that the influence of the
      cavity length L and the laser linewidth DeltaupsilonL on the ARW is dominantly
      related to the factor e-2piDeltaupsilonLneL/c, and under the finesse 88, the best
      ARW is obtained when there is a relation L.DeltaupsilonL~4*105  m.Hz.

PMID- 29216055
TI  - Unscented information filtering phase unwrapping algorithm for interferometric
      fringe patterns.
AB  - This paper proposes a new phase unwrapping (PU) algorithm based on an unscented
      information filter for interferometric fringes. The proposed algorithm is the
      result of combining an unscented information filter with a Levenberg-Marquardt
      method, a robust phase gradient estimator called the amended matrix pencil model,
      and an efficient quality-guided strategy based on heapsort. The unscented
      information filter, a new type of filter that has recently been well applied to
      traditional nonlinear object tracking fields, is introduced to estimate the
      unambiguous unwrapped phase of wrapped phase images for the first time, to the
      best of our knowledge. First, a recursive PU procedure based on an unscented
      information filter is established to perform PU and noise filtering at the same
      time by combining the unscented information filter and the amended matrix pencil
      model, where the amended matrix pencil model is applied to acquire phase gradient
      information needed for the recursive PU procedure. Second, the above recursive PU
      procedure is further optimized to improve the accuracy of the phase estimate by
      inserting the Levenberg-Marquardt method. This is also the first time that the
      Levenberg-Marquardt method is combined with the unscented information filter for
      the unwrapping of interferometric fringes, to the best of our knowledge. Finally,
      the efficient quality-guided strategy based on heapsort is used to efficiently
      route the path of the unwrapping procedure and to guide the proposed method to
      efficiently unwrap wrapped pixels along the path from the high-reliance region to
      the low-reliance region of the wrapped fringes. Results obtained with synthetic
      data and real data show more acceptable solutions with the proposed method,
      compared to some of the most used algorithms.

PMID- 29216056
TI  - Micro-motion detection of the 3-DOF precision positioning stage based on
      iterative optimized template matching.
AB  - This study presents a method for micro-motion detection of the three-degrees-of
      freedom (3-DOF; x, y, thetaz) precision positioning stage (PPS) based on
      iterative optimized template matching (IOTM). In this method, a micro-vision
      system (MVS) is constructed and employed to capture magnified images of the
      measured PPS's surface with high quality. In addition, an efficient and accurate
      IOTM algorithm, which includes a pyramid hierarchical matching step for
      generating the initial guess and an iterative searching step for 3-DOF fine
      matching, is proposed to detect the micro-motion of the 3-DOF PPS. The simulation
      results show that the locating accuracy of the translation component (TC) and
      rotation component of this algorithm can respectively reach 0.01 pixels and 0.01
      deg when the image quality is high and the initial guess is close to the real
      location. Measurement tests of a nano-PPS verify that the proposed method is
      practical and effective for 3-DOF micro-motion detection and the absolute
      accuracy of the TC of the MVS can easily reach the nanometer level.

PMID- 29216057
TI  - Multi-objective versus single-objective optimization frameworks for designing
      photonic crystal filters.
AB  - This paper proposes a novel framework for multi-objective optimization of
      photonic crystal (PhC) filters and compares it with a single-objective
      optimization approach. In this framework, an optimizer called the Multi-Objective
      Gray Wolf Optimizer has been utilized to automatically find the optimal designs.
      The proposed method is able to design any kind of PhC filter. As a case study, a
      new structure of super defect PhC filter for application in the wavelength
      division multiplexer (WDM) is designed using the framework. The results show that
      the proposed framework is comprehensive and able to find a significantly wide
      range of optimal designs for general and specific application, such as WDM with
      respect to each defined WDM standard.

PMID- 29216058
TI  - Wave properties in asymmetric single-negative-base photonic crystals.
AB  - We theoretically study wave properties for one-dimensional defective asymmetric
      photonic crystals, air/(AB)MG(BA)N/air, air/(AQ)MG(QA)N/air, and
      air/(BQ)MG(QB)N/air, where A is a lossy epsilon-negative material, B is a lossy
      mu-negative material, G and Q are dielectrics with different refractive indexes,
      and M and N are stack numbers with M?N. Special attention has been paid to their
      absorption spectra. It is found that at certain frequencies the absorption can
      exhibit unidirectional properties. Our calculated results show two kinds of
      unidirectional absorption peaks. One is a single absorption peak whose frequency
      depends on the thickness of defect layer G. For the other peaks, its frequency
      does not change when the defect layer's thickness changes. In addition, in the
      second kind of peaks, the peak numbers for forward and backward propagation are
      different, that is, there are (M-1) absorption peaks for forward propagation,
      while there are (N-1) absorption peaks for backward propagation. When the two
      kinds of unidirectional absorption peaks are merged, some new peaks appear, and
      both forward and backward propagation will have (M+N-1) absorption peaks.

PMID- 29216059
TI  - Analysis of dual coupler nested coupled cavities.
AB  - Coupled ring resonators are now forming the basic building blocks in several
      optical systems serving different applications. In many of these applications, a
      small full width at half maximum is required, along with a large free spectral
      range. In this work, a configuration of passive coupled cavities constituting
      dual coupler nested cavities is proposed. A theoretical study of the
      configuration is presented allowing us to obtain analytical expressions of its
      different spectral characteristics. The transfer function of the configuration is
      also used to generate design curves while comparing these results with analytical
      expressions. Finally, the configuration is compared with other coupled cavity
      configurations.

PMID- 29216060
TI  - Inverse conversion algorithm for an all-optical depth coloring camera.
AB  - Three-dimensional (3D) metrology has received a lot of attention from academic
      and industrial communities due to its broad applications, such as 3D contents, 3D
      printing, and autonomous driving. The all-optical depth coloring (AODC) camera
      has some benefits in computation load since it extracts depth information of an
      object fully optically. The AODC camera represents the depth of the object as a
      variation of wavelength, and spectroscopy is generally required to measure the
      wavelength. However, in the AODC camera, the color vector in RGB color space is
      convertible inversely into the wavelength after projection on the normalized rgb
      plane because the detected spectrum through the gating part has a narrow
      bandwidth as a result of the width of the slit in the projection part. In this
      paper, we propose an inverse conversion algorithm from RGB color to depth without
      spectroscopy. Experimental results are presented to confirm its feasibility.
      Also, some practical limitations are discussed, resulting from the nonlinearity
      of the response of the image sensor and the widths of the slits in the projection
      part and the gating part.

PMID- 29216061
TI  - Relationship between phosphor properties and chromaticity of phosphor-in-glass.
AB  - SiO2-B2O3-ZnO-Li2O glass and four types of phosphors (Y3Al5O12:Ce3+,
      (Sr,Ba)Si2O2N2:Eu2+, CaAlSiN3:Eu2+, and Lu3Al5O12:Ce3+) with different spectral
      distributions and thermal properties were prepared to achieve the desired color
      point based on the relationship between the thermal properties of phosphors and
      the microstructure of the phosphor-in-glass (PIG). The glass frit was mixed with
      various contents of phosphors (2.5, 5.0, 7.5, and 10.0 vol%) and then sintered to
      form a PIG. It was confirmed that the different pore properties of each PIG,
      caused by the difference in phosphor thermal properties, have a strong influence
      on the optical properties of the PIG. As the mass change of the phosphor
      increases, the scattering coefficient of the PIG also increases based on the
      variations in both pore size and porosity inside the plate. It is apparent that
      the scattering coefficient is strongly related to the path of converted light and
      blue light from the light-emitting diode (LED) chip; therefore, the ratio of
      transmittance to reflectance of each PIG is different, even if each PIG has the
      same phosphor content. These results indicate that achieving the target LED
      chromaticity is closely related to the phosphor characteristics and PIG's pore
      properties.

PMID- 29216062
TI  - Piezo-optic and elasto-optic properties of monoclinic triglycine sulfate
      crystals.
AB  - For the first time, to the best of our knowledge, we have experimentally
      determined all of the components of the piezo-optic tensor for monoclinic
      crystals. This has been implemented on a specific example of triglycine sulfate
      crystals. Based on the results obtained, the complete elasto-optic tensor has
      been calculated. Acousto-optic figures of merit (AOFMs) have been estimated for
      the case of acousto-optic interaction occurring in the principal planes of the
      optical indicatrix ellipsoid and for geometries in which the highest elasto-optic
      coefficients are involved as effective parameters. It has been found that the
      highest AOFM value is equal to 6.8*10-15  s3/kg for the case of isotropic acousto
      optic interaction with quasi-longitudinal acoustic waves in the principal planes.
      This AOFM is higher than the corresponding values typical for canonic acousto
      optic materials, which are transparent in the deep ultraviolet spectral range.

PMID- 29216063
TI  - Modeling of the petawatt PETAL laser chain using Miro code.
AB  - Miro software has been used intensively to simulate the Laser Megajoule (LMJ)
      with the treatment of amplification, frequency conversion, and both
      temporal/spatial smoothing of the beam for nanosecond pulses. We show that the
      software is able to model most relevant aspects of the petawatt PETAL laser chain
      in the subpicosecond regime, from the front-end to the focal spot with a
      broadband treatment of the amplification and compression stages, including
      chromatism compensation in the laser chain, segmentation and recombination of the
      beams on the second compression stage, and focusing by an off-axis parabola.

PMID- 29216064
TI  - Numerical simulation and experimental investigation of GaN-based flip-chip LEDs
      and top-emitting LEDs.
AB  - We demonstrate a GaN-based flip-chip LED (FC-LED) with a highly reflective indium
      tin oxide (ITO)/distributed Bragg reflector (DBR) ohmic contact. A transparent
      ITO current spreading layer combined with Ta2O5/SiO2 double DBR stacks is used as
      a reflective p-type ohmic contact in the FC-LED. We develop a strip-shaped SiO2
      current blocking layer, which is well aligned with a p-electrode, to prevent the
      current from crowding around the p-electrode. Our combined numerical simulation
      and experimental results revealed that the FC-LED with ITO/DBR has advantages of
      better current spreading and superior heat dissipation performance compared to
      top-emitting LEDs (TE-LEDs). As a result, the light output power (LOP) of the FC
      LED with ITO/DBR was 7.6% higher than that of the TE-LED at 150 mA, and the light
      output saturation current was shifted from 130.9  A/cm2 for the TE-LED to 273.8 
      A/cm2 for the FC-LED with ITO/DBR. Owing to the high reflectance of the ITO/DBR
      ohmic contact, the LOP of the FC-LED with ITO/DBR was 13.0% higher than that of a
      conventional FC-LED with Ni/Ag at 150 mA. However, because of the better heat
      dissipation of the Ni/Ag ohmic contact, the conventional FC-LED with Ni/Ag
      exhibited higher light output saturation current compared to the FC-LED with
      ITO/DBR.

PMID- 29216065
TI  - Integrated beam shaping and polarization beam combining design for fiber-coupled
      semiconductor laser stacks system.
AB  - The beam quality mismatch in the fast and slow axes of laser diode stacks limits
      their applications. An effective beam-shaping method was proposed based on a pair
      of step prisms. Using this technique, we can eliminate the lightless areas and
      achieve polarization multiplexing of laser diode stacks. Two laser diode stacks
      consisting of eight bars were coupled into a fiber with a core diameter of 200
      MUm and a numerical aperture of 0.22. The simulation results demonstrated that
      the output power can reach 1083 W and the optical-optical efficiency was 84.6%.

PMID- 29216066
TI  - Overlapped fiber-optic Michelson interferometers for simultaneous refractive
      index measurement at two sensing points.
AB  - We present a fiber refractometer based on the implementation of overlapped
      Michelson interferometers; the refractometer allows simultaneous refractive index
      measurement at two sensing points for samples discrimination. The fiber
      refractometer uses the Fresnel reflection in each fiber tip of the overlapped
      interferometers to generate the interference signal. Experimental results,
      implementing the two sensing points, for discrimination between non-contaminated
      and contaminated distilled water are presented. Despite the simplicity of the
      presented system, resolution and repeatability of 3*10-4 and 5*10-4 are obtained
      in a dip and read experiment using both sensing points simultaneously for
      refractive index measurement.

PMID- 29216067
TI  - Rapid calibration of a projection-type holographic light-field display using
      hierarchically upconverted binary sinusoidal patterns.
AB  - A projection-type holographic light-field (LF) display is a full-parallax, full
      color, and glass-free three-dimensional (3D) display with a holographic optical
      element and a projector. The display has unique characteristics, including
      transparency; however, a rapid calibration method has not yet been established.
      In this paper, we propose a rapid calibration method for a holographic LF display
      without sacrificing its accuracy. The proposed method performs calibration via
      the projection of binary sinusoidal patterns whose frequencies are iteratively
      and hierarchically upconverted. Compared to the conventional method, in the
      proposed method, the required number of projections is reduced from linear to
      logarithmic with the projector's resolution. We confirm the successful
      reconstruction of the 3D image using the proposed method.

PMID- 29216068
TI  - 16  Gbps random bit generation using chaos in near-symmetric erbium-doped fiber
      ring laser.
AB  - We demonstrate a bias-free random bit generator at 16 Gbps using chaos in a near
      symmetric erbium-doped fiber (EDF) ring laser. The laser consists of two EDFs,
      each pumped at 980 nm, two intracavity filters of central wavelength 1549.30 nm,
      and two 90:10 output couplers. The presence of chaos at the laser output is
      demonstrated by computing the largest Lyapunov exponent for different embedding
      dimensions. The laser outputs are photodetected and subtracted to generate an
      electrical difference signal, which is then sampled at 2 GSa/s and postprocessed
      to extract random bits at 16 Gbps. The random bits exhibit very low
      autocorrelation (~10-4) and have successfully passed all National Institute of
      Standards and Technology statistical tests and Diehard battery of tests.

PMID- 29216069
TI  - High-energy, stable single-frequency Ho:YAG ceramic amplifier system.
AB  - We demonstrate a 2090 nm single-frequency, high-energy, Q-switched Ho:YAG ceramic
      master oscillator and power amplifier system that contains two-stage amplifiers.
      The maximum single-frequency pulse energy is 55.64 mJ at a pulse repetition
      frequency of 200 Hz. The half-width of the pulse spectrum is measured to be 3.96
      MHz by a heterodyne technique. To the best of our knowledge, 55.64 mJ is the
      highest single-frequency output energy obtained from the Ho:YAG laser.

PMID- 29216070
TI  - Tunable plasmon-induced absorption in an integrated graphene nanoribbon side
      coupled waveguide.
AB  - By designing a novel graphene plasmonic band-pass filter with two gold ribbons,
      we have numerically and analytically investigated the transmission properties of
      plasmon-induced absorption (PIA) in a compact graphene nanoribbon side-coupled
      waveguide. The formation and evolution of the PIA window are dependent on the
      superposition of super resonances and the near-field coupling intensity between
      the designed two resonators. Interestingly, the induced absorption window not
      only can be engineered longitudinally in intensity, but also dynamically tuned
      horizontally in the resonant wavelength by changing the Fermi energy of the
      graphene layers. Optical time delay near 1.0 ps can be realized in the PIA
      window, which exhibits excellent slow light features. Double PIA resonance is
      also discussed. This result may have potential applications in graphene plasmonic
      switching and buffering.

PMID- 29216071
TI  - Features of the non-collinear one-phonon anomalous light scattering controlled by
      elastic waves with elevated linear losses: potentials for multi-frequency
      parallel spectrum analysis of radio-wave signals.
AB  - During subsequent development of the recently proposed multi-frequency parallel
      spectrometer for precise spectrum analysis of wideband radio-wave signals, we
      study potentials of new acousto-optical cells exploiting selected crystalline
      materials at the limits of their capabilities. Characterizing these wide-aperture
      cells is non-trivial due to new features inherent in the chosen regime of an
      advanced non-collinear one-phonon anomalous light scattering by elastic waves
      with significantly elevated acoustic losses. These features can be observed
      simpler in uniaxial, tetragonal, and trigonal crystals possessing linear acoustic
      attenuation. We demonstrate that formerly studied additional degree of freedom,
      revealed initially for multi-phonon regimes of acousto-optical interaction, can
      be identified within the one-phonon geometry as well and exploited for designing
      new cells. We clarify the role of varying the central acoustic frequency and
      acoustic attenuation using the identified degree of freedom. Therewith, we are
      strongly restricted by a linear regime of acousto-optical interaction to avoid
      the origin of multi-phonon processes within carrying out a multi-frequency
      parallel spectrum analysis of radio-wave signals. Proof-of-principle experiments
      confirm the developed approaches and illustrate their applicability to innovative
      technique for an advanced spectrum analysis of wideband radio-wave signals with
      the improved resolution in an extended frequency range.

PMID- 29216072
TI  - High-power self-mode-locked Pr:YLF visible lasers.
AB  - We demonstrate efficient self-mode-locked green and red lasers with repetition
      rates of tens and hundreds of megahertz in a Pr:YLF crystal. Using double-end
      blue-diode-pumped geometry, more than 0.68 W average output power at 522 nm and
      more than 1.44 W at 639 nm are obtained, which are believed to be the highest
      average output powers for mode-locked praseodymium lasers operating in the
      visible wavelength region.

PMID- 29216073
TI  - Plasmon-induced transparency based on a triangle cavity coupled with an ellipse
      ring resonator.
AB  - In this paper, a novel compact plasmonic system is introduced to realize the
      phenomenon of plasmon-induced transparency. The proposed device consists of a
      triangle defect coupled with an ellipse-ring resonator based on a metal-insulator
      metal platform. By the finite-difference time-domain method, the transmission
      characteristics are numerically studied in detail. In order to verify the
      simulation results, the coupled mode theory is utilized. In the following, the
      effect of geometrical parameters, namely, the major and minor radii of the
      ellipse-ring and the gap between cavities, are investigated. Moreover, the
      fundamental factors of transmission spectra including intrinsic Drude loss and
      refractive index of dielectric region are studied. As a result, the transmission
      peak is obtained near 70% and the full width at half-maximum is close to 28 nm.
      The sensitivity and figure of merit of the proposed structure are 860 nm/RIU and
      31.6  RIU-1, respectively. The mentioned compact structure has the ability and
      potential to be used in integrated optical circuits like slow light devices,
      nanoscale filters and nanosensors.

PMID- 29216074
TI  - Diffraction mechanism of a light-diffusing film with an alternate-polymer-layer
      structure.
AB  - A diffraction mechanism, and an optical model to reflect that mechanism, for a
      light-diffusing film with an alternate-polymer-layer structure was proposed and
      validated. According to this model, the film forms an angular distribution of
      light intensity that is almost constant in a certain scattering-angle (cutoff
      angle) range and drastically decreases outside that range; that is, the profile
      is similar to a trapezoid. Although the trapezoid intensity distribution (TID) is
      a fundamental distribution of the film, the mechanism to form the TID has not
      previously been clarified. A key mechanism is that the refractive-index
      distribution of the layer structure is expressed as stacked phase gratings, some
      of which should diffract zeroth-order light to higher orders strongly, and the
      repetition of this multiple diffraction spreads light over the whole cutoff angle
      range, thereby generating the TID. To verify the proposed mechanism, intensity
      distributions were calculated by using the proposed model. The calculation
      results indicate that the proposed model reproduces the TID.

PMID- 29216075
TI  - Spectral response of Bragg gratings in multimode polymer waveguides.
AB  - A means to calculate the multimodal spectral response of Bragg gratings in
      general non-circular multimode waveguides is proposed. To illustrate the power of
      the technique, the spectra of two Bragg temperature sensors are numerically
      calculated in which coupling between 100 modes is considered. It is shown how the
      Bragg wavelength in multimode Bragg grating waveguides is affected by the number
      of modes and energy distribution among them. Good matching of the simulated
      spectrum of a multimode Bragg grating on a planar inverted rib waveguide to the
      measured spectrum is seen.

PMID- 29216076
TI  - Security validation based on orthogonal polarization multiplexing in three
      dimensional space.
AB  - To enhance the security and practicality of the optical validation technique, a
      multiple-level security validation method is proposed based on orthogonal
      polarization multiplexing in a three-dimensional (3D) space. First, the original
      image is partitioned into two complementary images. Each image is divided into
      several subblocks. Then, two phase-only masks are generated by adopting the
      multiple diffractive planes and multiple signal windows phase-retrieval algorithm
      to reproduce a 3D diffraction field with all of the subblocks randomly
      distributed in specific locations. One of the phase masks is taken as the fixed
      system lock. The other one is preserved to act as the validation key. At last,
      the two diffraction beams of two phase-only masks are converted into orthogonal
      polarization states when illuminated by a collimated wave. As a result, the
      simultaneous control of both intensity and polarization distributions in desired
      longitudinal planes and transversal positions is achieved. A 3D polarization
      mapping protocol is established to generate the 3D polarization key. During
      validation, both the validation key and the 3d polarization key must be correct
      for a person to receive access permission. Experimental results show that the
      method is easy to implement and offers multiple-level validation functionality.

PMID- 29216077
TI  - High photon conversion efficiency continuous wave lasing in an optically pumped
      I2 hollow fiber gas laser in the visible region.
AB  - Continuous wave lasing in the visible spectral region from a molecular iodine
      filled hollow core photonic crystal fiber is demonstrated. More than an order of
      magnitude improvement in photon conversion efficiency has been achieved compared
      to previous nonfiber-based geometries in this spectral region. The laser shows
      strong coupling of pump and laser polarization.

PMID- 29216078
TI  - Onsite multikilowatt laser power meter calibration using radiation pressure.
AB  - We have demonstrated the calibration of a thermal power meter against a radiation
      pressure power meter in the range of 20 kW in a manufacturing test environment.
      The results were compared to a traditional calorimeter-based laboratory
      calibration undertaken at the National Institute of Standards and Technology. The
      results are reported, and the effects of nonideal conditions typical of
      measurements in low-stability environments are discussed.

PMID- 29216079
TI  - Theoretical investigation of a five-band terahertz absorber based on an
      asymmetric split-ring resonator.
AB  - A simple five-band terahertz metamaterial perfect absorber, composed of an
      asymmetric double-gap square split ring and a metallic ground plate spaced by a
      thin polyimide dielectric layer, is proposed and theoretically investigated. The
      results show that it can perform absorption peaks at five resonant frequencies
      whose peaks average 98.85%. The perfect absorption is mainly attributed to the
      combined effect of LC, dipole, and surface response of the structure. Compared to
      previously reported multiband absorbers, our design only has a single and compact
      structure, which can drastically simplify the design and fabrication process.
      Furthermore, the resonance absorption properties of the absorber can be tuned by
      changing the geometric parameters of the structure. Such a simple and effective
      design holds great promise for potential applications in spectroscopic imaging,
      biological sensing, and detecting of drugs and explosives.

PMID- 29216080
TI  - Modeling near-null testing method of a freeform surface with a deformable mirror
      compensator.
AB  - We present and analyze a new measurement method of freeform surfaces with a
      deformable mirror (DM), which functions as a wavefront compensator. We discuss
      the maximum slope compensation of a DM in the first-order approximation and
      derive how to calculate the ideal DM form. A constrained optimization procedure
      is conducted to ensure the actual DM form fits the ideal DM form as closely as
      possible. To demonstrate the feasibility and understand the measurable range of
      our method, we evaluate freeform surfaces with a single Zernike term, the first
      36 random Zernike terms, and 230 random Zernike terms. A tolerance analysis of
      the DM position is carried out to show the effect of the tilt and the decenter of
      the DM on the measurement accuracy. Our studies show that the proposed system is
      very flexible for freeform surface metrology.

PMID- 29216081
TI  - Fiber-integrated refractive index sensor based on a diced Fabry-Perot micro
      resonator.
AB  - We report on a fiber-integrated refractive index sensor based on a Fabry-Perot
      micro-resonator fabricated using simple diamond blade dicing of a single-mode
      step-index fiber. The performance of the device has been tested for the
      refractive index measurements of sucrose solutions as well as in air. The device
      shows a sensitivity of 1160 nm/RIU (refractive index unit) at a wavelength of
      1.55 MUm and a temperature cross-sensitivity of less than 10-7  RIU/ degrees C.
      Based on evaluation of the broadband reflection spectra, refractive index steps
      of 10-5 of the solutions were accurately measured. The conducted coating of the
      resonator sidewalls with layers of a high-index material with real-time
      reflection spectrum monitoring could help to significantly improve the sensor
      performance.

PMID- 29216082
TI  - On-stream analysis of iron ore slurry using laser-induced breakdown spectroscopy.
AB  - On-stream analysis of the element content in ore slurry has important
      significance in the control of the flotation process and full use of raw
      materials. Therefore, techniques that can monitor the chemistry in slurries
      online are required. Laser-induced breakdown spectroscopy (LIBS) is one of the
      potential approaches to online measurements due to its capability of in situ and
      real-time analysis. However, using LIBS for on-stream analysis of slurries is
      challenging due to the issues such as surface ripples, sample splashing,
      sedimentation, etc. To address these problems, we developed a slurry circulation
      system. The effects of slurry flow rate on LIBS spectra were investigated to
      achieve the optimal detecting surface for better repeatability of LIBS. The
      coefficient of determination R2 of the calibration curve for Fe element is 0.982,
      and the limit of detection of Fe element was estimated to be 0.075 wt. % under
      the optimized experimental parameters. The results show that this slurry
      circulation system is applicable to the on-stream slurry analysis.

PMID- 29216083
TI  - Linearly frequency-tuned LD-pumped Nd:YVO4 laser with an 18-GHz broadband tuning
      range.
AB  - A continuously frequency-tuned laser diode end-pumped Nd:YVO4 laser at 1064 nm is
      demonstrated. A coated etalon and a piezoelectric-transducer (PZT) are utilized
      for coarse and fine frequency tuning, respectively. Broadband and linear
      frequency tuning without mode hops is conducted by the synchronous adjustment of
      the etalon and the PZT. Dependence of the frequency excursion on the displacement
      of the PZT and the tilting angle of the etalon are theoretically and
      experimentally investigated. A linear frequency tuning range up to 18 GHz without
      mode hops or frequency overlaps in a one-way non-stopped scanning is obtained.
      The maximum output power is 930 mW at 1064 nm, and the average frequency tuning
      speed is 1.24 GHz/s. Standard deviation of the frequency variation to a linear
      frequency tuning is estimated to be 186 MHz, indicating a high tuning linearity.

PMID- 29216084
TI  - Reduction of the effects of angle errors for a channeled spectropolarimeter.
AB  - Angle errors of high-order retarders will decrease the accuracy of a channeled
      spectropolarimeter. This paper presents an easily implemented and widely
      applicable method for reducing the effects of the angle errors. First, we
      theoretically derive a modified reconstruction model to express and analyze the
      effects of the angle errors. Based on the modified reconstruction model and
      current reference beam calibration technique, we put forward the modified
      reference beam calibration technique to reduce the effects of the angle errors.
      This method can calculate the angle errors by employing the amplitude terms,
      which have been ignored in the results of the current reference beam calibration.
      The effectiveness of the presented method is verified by numerical simulations,
      which show that the demodulated deviations of polarization parameters have been
      reduced by one order of magnitude. Experiments are further implemented to
      validate the proposed method. The convenience and wide applicability of the
      presented method make it suitable for regular correction of the instrument,
      especially for the case on track.

PMID- 29216085
TI  - Hybrid artificial bee colony algorithm for parameter optimization of five
      parameter bidirectional reflectance distribution function model.
AB  - A hybrid artificial bee colony (ABC) algorithm inspired by the best-so-far
      solution and bacterial chemotaxis was introduced to optimize the parameters of
      the five-parameter bidirectional reflectance distribution function (BRDF) model.
      To verify the performance of the hybrid ABC algorithm, we measured BRDF of three
      kinds of samples and simulated the undetermined parameters of the five-parameter
      BRDF model using the hybrid ABC algorithm and the genetic algorithm,
      respectively. The experimental results demonstrate that the hybrid ABC algorithm
      outperforms the genetic algorithm in convergence speed, accuracy, and time
      efficiency under the same conditions.

PMID- 29216086
TI  - Theoretical investigation on mid-infrared cascaded Raman fiber laser based on
      tellurite fiber.
AB  - A numerical simulation of third-order cascaded Raman fiber laser based on
      tellurite fiber at the 2-5 MUm waveband is presented. The Raman fiber laser can
      be optimized with the most suitable tellurite fiber length of 0.5-1.0 m and the
      most reasonable reflectivity of the third-order Stokes output FBG32 of 10%-20%.
      We demonstrate numerically that the third-order Stokes wave can reach the maximum
      average power of 45.2 W and the maximum optical conversion efficiency of 45.2%,
      corresponding to the FBG32 reflectivity of 10% and the tellurite fiber length of
      0.3 m with the attenuation of 0.85 dB/m, when pumped by 2 MUm light with the
      average power of 100 W. Our simulated results provide valuable theoretical
      guidance for the design and experiment of tellurite Raman fiber laser at a mid
      infrared waveband.

PMID- 29216087
TI  - Ultrastable offset-locked frequency-stabilized heterodyne laser source with water
      cooling.
AB  - An ultrastable frequency-stabilized He-Ne laser with a water-cooling structure
      has been developed for a high-speed and high-accuracy heterodyne interferometer.
      To achieve high frequency stability and reproducibility, a two-mode He-Ne laser
      was offset locked to an iodine-stabilized laser. An improved synchronous multi
      cycle offset frequency-measurement method with a gate time of an integer multiple
      of the modulation period was employed to remove the frequency-modulation effect
      on the offset-frequency counter. A water-cooling structure based on the double
      helix structure was established to provide a stable and low-temperature working
      environment. This structure can remarkably reduce the frequency instability
      arising from the environmental temperature variation and the thermal pollution
      released from the laser to the environment. The experimental results indicate
      that the frequency stability according to the Allen variance is better than
      2.3*10-11 (tau=10  s) and the frequency reproducibility is better than 4.5*10-10.

PMID- 29216088
TI  - Extending capture range for piston retrieval in segmented systems.
AB  - Image-based wavefront sensing is a powerful technique for measuring the
      aberrations of optical systems and surfaces. It often fails for segmented systems
      with large piston errors per segment. We propose a method for finding these
      errors using broadband light and a specialized grid search as part of a more
      global search. We show that this method has a high rate of success for a case
      where nonlinear optimization gets stuck in local minima. We also explore points
      of failure.

PMID- 29216089
TI  - Stitching test of large flats by using two orthogonally arranged wavefront
      interferometers.
AB  - The most challenging problem in the stitching test of large flats with a small
      aperture interferometer is the accumulation effect of the second-order error. As
      it is approximately enlarged by the square of the ratio of full aperture size to
      subaperture size, a very small amount of the second-order error in the reference
      surface of a transmission flat can be accumulated and gets far from negligible
      when the subaperture is far smaller than the full aperture. We present here a
      solution by using two orthogonally arranged wavefront interferometers. One is
      responsible for a subaperture test and the other for the simultaneous measurement
      of relative tilts. Because the accumulation effect originates from the lateral
      shift of the second-order error, only the tilt along the subaperture scanning
      direction needs to be measured accurately. It is no longer determined by
      stitching optimization instead to avoid the error accumulation. Piston and tilt
      perpendicular to the scanning direction are still determined by stitching
      optimization. The method is experimentally verified and compared to the stitching
      test with the reference surface error calibrated out, both referenced to the full
      aperture test result obtained with a 24-inch interferometer.

PMID- 29216090
TI  - Comparison of spatially and temporally resolved diffuse transillumination
      measurement systems for extraction of optical properties of scattering media.
AB  - This paper discusses the main differences between two different methods for
      determining the optical properties of tissue optical phantoms by fitting the
      spatial and temporal intensity distribution functions to the diffusion
      approximation theory. The consistency in the values of the optical properties is
      verified by changing the width of the recipient containing the turbid medium; as
      the optical properties are an intrinsic value of the scattering medium,
      independently of the recipient width, the stability in these values for different
      widths implies a better measurement system for the acquisition of the optical
      properties. It is shown that the temporal fitting method presents higher
      stability than the spatial fitting method; this is probably due to the addition
      of the time of flight parameter into the diffusion theory.

PMID- 29216091
TI  - Experimental observations of a laser suppression imaging system using pupil-plane
      phase elements.
AB  - To help diminish the undesirable effects of laser irradiation on an imaging
      sensor, a pupil-plane phase element was introduced to broaden the point spread
      function, thereby reducing the focused laser irradiance. A sharpened image was
      subsequently restored via Wiener deconvolution. Successful experimental
      demonstrations employing a spatial light modulator in the pupil plane are
      reported for the vortex, axicon, and cubic phase. Furthermore, to circumvent
      information loss owing to zero values in the modulation transfer function, we
      demonstrate how images with different phase elements, combined with a joint
      deconvolution operation, provide an improved image.

PMID- 29216092
TI  - Accuracy evaluation of demodulation results of fiber Bragg grating sensors.
AB  - Fiber Bragg grating (FBG) sensors are prone to spectral distortions in practical
      applications, which may cause large demodulation errors. There are many
      algorithms demodulating FBG spectra, but no approach is able to evaluate
      demodulation results under spectral distortions. To address this problem, four
      spectral indices are comparatively utilized to quantify distortions of spectra.
      Seven representative demodulation algorithms are adopted to analyze impacts of
      various simulated distorted spectra. Simulation results show that the side-mode
      suppression ratio (SMSR) of the spectrum is the most suitable spectral index for
      accuracy evaluation of demodulation results. In particular, when SMSR is larger
      than 6.3 dB, demodulation results will be accurate, and they are inaccurate when
      SMSR is smaller than 2.1 dB. The effectiveness of the proposed evaluation
      approach is validated with fatigue experiments of 9 FBG sensors.

PMID- 29216093
TI  - 140  MUm single-polarization passive fully aperiodic large-pitch fibers operating
      near 2 MUm.
AB  - In this paper, we demonstrate a single-polarization feature out of passive very
      large-mode-area fully aperiodic large-pitch fibers. It has been previously shown
      theoretically that one of the two polarizations of the fundamental mode is
      selectively coupled to a cladding mode. This coupling does not require fiber
      bending, which permits us to avoid any decrease in mode effective area. The
      coupling is achieved owing to boron-doped silica inclusions implemented into the
      microstructured cladding and acting as stress-applying parts. This mechanism has
      been assessed experimentally in this work using fibers of two different core
      diameters: 60 MUm and 140 MUm, providing mode field areas of 3637  MUm2 and
      14,590  MUm2, respectively, at 1942 nm. The tested fibers have a length of 45 cm
      and an outer diameter exceeding 1 mm, yielding rod-type fibers. Each sample has
      been characterized using an unpolarized laser source emitting at 1942 nm. This
      laser, based on a thulium-doped large-mode-area step-index fiber, has a spectral
      bandwidth of about 0.5 nm. After passing through a piece of the passive fiber, a
      polarization extinction ratio higher than 16 dB has been achieved.

PMID- 29216094
TI  - Analysis and reduction of the TDI CCD charge transfer image shift.
AB  - Based on the description of the charge transfer process of a time delay
      integration charge coupled device (TDI CCD), it is pointed out that the relative
      displacement of the target image and the transferred charge introduces the charge
      transfer image shift problem in a line transfer period, which leads to the
      decrease of the modulation transfer function (MTF) in the scanning direction.
      Based on the basic definition of MTF, the charge transfer image shift model of
      the TDI CCD is established. According to the quantitative calculation of this
      model, the MTF curves of the three-phase TDI CCD are obtained under the condition
      of different pulse widths of computer interface (CI) signals. The MTF changes
      with the pulse width of CI signals, and the maximum value at the spatial Nyquist
      frequency is obtained when the CI signals are equally spaced, which is difficult
      to achieve in the actual system because of the limitation of computed radiography
      readout signals. In this paper, we present the improved TDI CCD driving timing,
      which makes it possible to realize the equal interval distribution of CI signals
      by adjusting the technology compatibility kit signal. Finally, the experimental
      platform is built, and the MTF curves are calculated from the obtained target
      images. The result is consistent with the theoretical model.

PMID- 29216095
TI  - Absorption measurements in optical coatings by lock-in thermography.
AB  - We evaluate and apply lock-in thermography as a method to quantitatively evaluate
      absorption losses of optical coatings. The principle of the method consists of
      applying periodically modulated laser intensity on the coatings and to monitor
      the periodic surface temperature evolution with an infrared camera. By
      application of a lock-in correlation procedure and using calibrated absorption
      samples, it is possible to obtain quantitative absorption values and to obtain
      absorption mappings with spatial resolution that depends on the optical
      configuration. Numerical simulations and experiments were performed in the case
      of 10-60 W laser irradiation at 1060 nm on different single layer coatings and
      highly reflective mirrors. In the tested conditions, the measurement of
      absorption down to 1 ppm level could be reached. The advantages, limitations, and
      potential applications of the technique are discussed.

PMID- 29216096
TI  - Refractive index profilometry using the total internally reflected light field.
AB  - A full-field polarization-based technique is presented for quantitative
      evaluation of the spatial distribution of the refractive index in macro and micro
      samples. The sample is mounted on a glass-air interface of a prism, illuminated
      by a linearly polarized collimated light beam, and two intensity frames are
      digitally recorded with specific orientations of an analyzer. The pair of
      intensity data frames captured with this simple setup is combined through an
      algorithm specially developed for the purpose, to yield the phase difference
      between the transverse electric and transverse magnetic components of the total
      internally reflected light field. The phase difference is then related to the
      refractive index of the sample. Experimental results for refractive index
      variations in a laser-etched glass plate and red blood corpuscles are presented.
      One of the salient features of the proposed technique is that the depth of
      measurement is dependent on the penetration depth of the sample's evanescent
      field, which is typically of the order of a few hundred nanometers, thereby
      facilitating refractive index measurements along a thin section of the sample.

PMID- 29216097
TI  - Illumination-related errors in limited-angle optical diffraction tomography.
AB  - In the paper, the design and tolerances of optical systems and scanning
      components used in limited-angle optical diffraction tomography are analyzed in
      order to improve the performance of the measurement systems and to encourage the
      application of tomography as a standard method for quantitative analysis of 3D
      refractive index distribution in biological microstructures. The first part of
      the presented analysis consists of component selection for the scanning device
      and optical system in the illumination part of the setup and the influence of the
      illumination wavefront on reconstruction quality. In the second part, the
      sensitivity of the tomographic reconstruction quality to three representative
      measurement-related errors based on synthetic data is demonstrated. Finally, a
      configuration of the system, selected to minimize reconstruction errors, is
      proposed and alignment tolerances simulated using the Monte Carlo method are
      provided.

PMID- 29216098
TI  - Planar self-calibration for stereo cameras with radial distortion.
AB  - In this paper, we present a robust technique of stereo calibration using
      homography constraints. Our method is novel as stereo calibration is performed by
      solving a polynomial equation system including two radial distortion parameters,
      using a minimal number of five image point correspondences. This enables us to
      calibrate from only a pair of stereo images of a planar scene, and to provide the
      exact algebraic solution to the stereo calibration problem. The minimal case
      solution is useful to reduce the computation time and increase the calibration
      robustness when using random sample consensus (RANSAC) from the correspondences
      of the stereo image pair. Further, a non-linear parameter optimization for the
      intrinsic and extrinsic parameters of stereo cameras is performed using the
      inliers, which are determined after RANSAC. In addition, our method can achieve
      more robust calibration results with multiple stereo image pairs by performing
      joint optimization. In contrast to the previous stereo calibration methods, our
      method works without requiring any special hardware and has no problems with one
      stereo image pair, even corrupted by severe radial distortions. Finally, by
      evaluating our method on both synthetic and real scene data, we demonstrate that
      our method is both efficient and accurate for stereo calibration.

PMID- 29216099
TI  - Analysis of weighted subspace fitting and subspace-based eigenvector techniques
      for frequency estimation for the coherent Doppler lidar.
AB  - Since the periodogram maximum (PM) algorithm fails to provide consistent
      estimates, more robust techniques are developed, especially in a low signal-to
      noise ratio (SNR) regime. The methods are formulated in a subspace fitting-based
      framework, such as the eigenvector (EV) method and the proposed weighted subspace
      fitting (WSF) method by introducing an optimal weighting matrix, which exploits
      the low-rank properties of the covariance matrix of the coherent Doppler lidar
      echo data. Simulation results reveal that the number of the reliable estimates by
      the WSF method is more than the other two methods, and the standard deviation is
      the smallest. Furthermore, the predicted best-fit Gaussian model for the
      probability density function of the estimates has a narrower spectral width than
      that of PM and EV methods. Experimental results also validate the simulation
      results, which show that the WSF approach outperforms the PM and EV algorithms in
      the furthest detectable range. The proposed method improves the detection range
      approximately up to 14.2% and 26.6% when compared to the EV method and the PM
      method, respectively. In conclusion, the proposed method can reduce the
      statistical uncertainties and enhance the accuracy in wind estimation
      specifically for a low SNR regime.

PMID- 29216101
TI  - Three-dimensional range geometry compression via phase encoding.
AB  - One of the state-of-the-art methods for three-dimensional (3D) range geometry
      compression is to encode 3D data within a regular 24-bit 2D color image. However,
      most existing methods use all three color channels to solely encode 3D data,
      leaving no room to store other information (e.g., texture) within the same image.
      This paper presents a novel method which utilizes geometric constraints, inherent
      to the structured light 3D scanning device, to reduce the amount of data that
      need be stored within the output image. The proposed method thus only requires
      two color channels to represent 3D data, leaving one channel free to store
      additional information (such as a texture image). Experimental results verify the
      overall robustness of the proposed method. For example, a compression ratio of
      3038:1 can be achieved, versus the STL format, with a root-mean-square error of
      0.47% if the output image is compressed with JPEG 80%.

PMID- 29216100
TI  - Emission spectroscopy of expanding laser-induced gaseous hydrogen-nitrogen
      plasma.
AB  - Microplasma is generated in an ultra-high-pure H2 and N2 gas mixture with a
      Nd:YAG laser device that is operated at the fundamental wavelength of 1064 nm.
      The gas mixture ratio of H2 and N2 is 9 to 1 at a pressure of 1.21 +/- 0.03 105
      Pa inside a chamber. A Czerny-Turner-type spectrometer and an intensified charge
      coupled device are utilized for the recording of plasma emission spectra. The
      line-of-sight measurements are Abel inverted to determine the radial
      distributions of electron number density and temperature. Recently derived
      empirical formulas are utilized for the extraction of values for electron
      density. The Boltzmann plot and line-to-continuum methods are implemented for the
      diagnostic of electron excitation temperature. The expansion speed of the plasma
      kernel maximum electron temperature amounts to 1  km/s at a time delay of 300 ns.
      The microplasma, initiated by focusing 14 ns, 140 mJ pulses, can be described by
      an isentropic expansion model.

PMID- 29216102
TI  - Wave diffraction by a reflectionless half-plane.
AB  - The concept of reflectionless surface is put forth, and its reflection and
      transmission coefficients are determined by using the scattered geometrical
      optics fields of transmissive and perfectly electric conducting surfaces. The
      boundary condition of the surface is introduced. The scattering problem of plane
      waves by a reflectionless half-screen is studied. The solution is investigated
      numerically.

PMID- 29216103
TI  - Digital quantification of DNA by mapping polarization degree related with coding
      gold nanorods.
AB  - The development of highly sensitive and low-cost methods for detecting DNA is of
      critical importance. Here, we describe a strategy for the highly sensitive and
      low-cost digital detection of target DNA. Individual DNA molecules were encoded
      with a single gold nanorod (Au NR), which was then separated and enriched using
      the magnetic immune-separation process, followed by dehybridization and
      dispersion into a buffer solution and immobilization on glass slides for
      polarized dark-field microscopic imaging. With the imaging we can get the first
      three data sets of the Stokes vector, and the experimental degree of the linear
      polarization of the light scattered by the Au NR was obtained. Using the Monte
      Carlo simulation program, the Muller matrix of the Au NRs was simulated and the
      simulated degree of the linear polarization was calculated to be 0.58. Based on
      the experimental and simulated degree of the linear polarization, the Au NRs were
      identified and quantified with an in-house Matlab program, and the concentration
      of the target DNA at the femtomolar level was therefore achieved.

PMID- 29216104
TI  - Simplified freeform optics design for complicated laser beam shaping.
AB  - Control of the optical fields of laser beams, i.e., laser beam shaping, is of
      great importance to many laser applications. Freeform optics offers plenty of
      advantages for complex beam shaping requirements, including precise beam control,
      energy efficiency, compact structure, and relatively low cost. We present a
      modified ray-mapping method to simplify the freeform optics design for
      complicated optical field control and achieve a challenging task of producing two
      prescribed beam profiles on two successive target planes. This method begins by
      calculating an approximate output ray sequence that connects the two prescribed
      beam profiles and a corresponding input ray sequence. After setting an initial
      profile of the first freeform optical surface on the input ray sequence, we can
      obtain the second freeform optical surface based on the optical path length
      constancy between the given input wavefront and the computed output wavefront.
      Then, we can acquire all the normal vectors of the first freeform optical surface
      using Snell's law and approximately reconstruct the first freeform optical
      surface by solving a relationship between the surface points and normal vectors
      using a fast least squares method. The surface construction process is repeated
      until the stop criterion is satisfied. We design three freeform lenses, and Monte
      Carlo simulations demonstrate their abilities of simultaneously producing two
      challenging beam profiles from a divergent Gaussian beam.

PMID- 29216105
TI  - Optical fiber shape sensing of polyimide skin for a flexible morphing wing.
AB  - This paper presents the 3D shape sensing of polyimide thin film skin for a
      flexible morphing wing using fiber Bragg grating (FBG) sensors. The calibration
      curves of the FBG sensors are measured experimentally to ensure relative accurate
      conversion between Bragg wavelength shift (BWS) and bending curvature of the
      polyimide skin. The reflection spectra of the FBG sensors are measured at
      different airfoil profiles, and the variation tendency of the BWS values with the
      airfoil profiles are analyzed. The bending curvatures of the polyimide thin film
      skin at different airfoil profiles are calculated using the measured BWS values
      of the FBG sensors and the linear interpolation algorithm. The 3D shapes of the
      polyimide skin at different airfoil profiles are reconstructed based on the
      measured bending curvatures and the interpolation and curve fitting functions.
      The 3D precise visual measurements are conducted using a digital photogrammetry
      system, and then the correctness of the shape reconstruction results are
      verified. The results prove that the maximum error between the 3D visual and FBG
      measurements is less than 5%. The FBG sensing method is effective for the shape
      sensing of polyimide skin for flexible morphing wing.

PMID- 29216106
TI  - Full four-dimensional and reciprocal Mueller matrix bidirectional reflectance
      distribution function of sintered polytetrafluoroethylene.
AB  - We measured the Mueller matrix bidirectional reflectance distribution function
      (BRDF) of a sintered polytetrafluoroethylene (PTFE) sample over the scattering
      hemisphere for six incident angles (0 degrees -75 degrees  in 15 degrees  steps)
      and for four wavelengths (351 nm, 532 nm, 633 nm, and 1064 nm). The data for each
      wavelength were fit to a phenomenological description for the Mueller matrix
      BRDF, which is an extension of the bidirectional surface scattering modes
      developed by Koenderink and van Doorn [J. Opt. Soc. Am. A.15, 2903
      (1998)JOAOD60740-323210.1364/JOSAA.15.002903] for unpolarized BRDF. This
      description is designed to be complete, to obey the appropriate reciprocity
      conditions, and to provide a full description of the Mueller matrix BRDF as a
      function of incident and scattering directions for each wavelength. The
      description was further extended by linearizing the surface scattering mode
      coefficients with wavelength. This data set and its parameterization provides a
      comprehensive on-demand description of the reflectance properties for this
      commonly used diffuse reflectance reference material over a wide range of
      wavelengths.

PMID- 29216107
TI  - Fabrication of ultra-high numerical aperture GeO2-doped fiber and its use for
      broadband supercontinuum generation.
AB  - We report the fabrication, characterization, and application (broadband
      supercontinuum [SC] generation) of ultra-high numerical-aperture heavily (50 mol.
      %) GeO2-doped optical fiber, obtained through a modified chemical vapor
      deposition process and rod-in-tube method. The formation of Ge-related
      diamagnetic defect centers, such as germanium oxygen defect centers (GeODC) with
      nonbridging lone electron pairs, confirmed by x-ray photoelectron spectroscopy
      and optical absorption studies, inducing hypolarizable local dipoles, may be
      responsible in boosting the nonlinear effects and enhancing stimulated Raman
      scattering at pumping with high-power pulses, culminating in generation of
      broadband SC generation. The SC spans toward the Stokes side up to 2.4 MUm, under
      the action of ns-range pulses launched from a smartly Q-switched erbium-doped
      fiber laser with operation wavelength (1.56 MUm) matching the zero-dispersion
      wavelength of the high GeO2-doped fiber.

PMID- 29216108
TI  - Phase retrieval in moire volume computed tomography based on spatial phase
      shifting by triple-crossed gratings.
AB  - Due to its advantages of nonintrusiveness, wide measurement range, and
      insensitivity to variation, Moire deflectometry is a powerful tool for
      quantitative measurement of a flow field's physical parameters such as density
      and temperature. Moire volume computed tomography (MVCT), combining the moire
      deflectometry and volume optical computed tomography (VOCT), can realize real
      three-dimensional parameters reconstruction, in which the radial derivatives
      extraction of the projected phase is of great importance. In this paper, a
      spatial phase-shifting-interferometry-based MVCT system was proposed to extract
      the radial shearing phase distribution. The system is simple and compact, and
      consists of three crossed gratings and lenses, with no wave plates or polarizers
      introduced. Via using a 4-f system, the optical path was shortened, and four
      spatial phase-shifting grid moire projections can be obtained simultaneously.
      Each grid interferogram was filtered and separated into two linear interferograms
      in two orthogonal directions. Moreover, a two-step spatial phase-shifting
      algorithm was applied to obtain the first-order derivative phase in two mutually
      perpendicular directions, respectively. Simulations were implemented to verify
      the feasibility and accuracy of the proposed phase retrieval method. The measured
      results for the radial first-order partial derivative of the phase projection of
      a propane flame in the experimental VOCT system are presented.

PMID- 29216109
TI  - Lattice-induced modulators at terahertz frequencies.
AB  - We measured the transmission spectra of an array of split-ring resonators (SRRs)
      up to 10 terahertz for parallel and perpendicular polarizations. Calculations of
      the lattice and plasmon mode dispersion relations, in combination with
      electromagnetic simulations, confirm the presence of multiple higher-order
      lattice and plasmon modes. We modify the quality factor of higher-order plasmon
      resonances by modulating the lattice-plasmon mode coupling via changes in the
      period of the array. We also propose single frequency switches and a broadband
      dual-state amplitude modulator based on structured illumination that actively
      modifies the period of the SRR array.

PMID- 29216110
TI  - Resonant cavities with phase-changing materials.
AB  - Phase changing materials are commonly used for optical switching, limiting, and
      sensing. In many important cases, the change in the transmission characteristics
      of the optical material is caused by light-induced heating. We demonstrate that
      the incorporation of such optical materials in judiciously designed photonic
      structures can dramatically alter the light-induced phase change, as well as the
      transmission characteristics of the entire photonic structure. Possible practical
      implications are discussed.

PMID- 29216111
TI  - Effect of dark counts on single-photon heralding with quasi-number-resolving
      detection schemes.
AB  - We consider photon heralding with quasi-number-resolving detection schemes and
      account for detection efficiencies and dark count probabilities. With a
      straightforward formalism, we develop closed-form expressions for the heralding
      probability, photon number distribution of the resulting heralded state, and
      fidelity of this heralded state to a single-photon state. We calculate that this
      fidelity has a maximum as a function of the number of multiplexed detection modes
      and that, for experimental configurations in which the maximum is reached for
      quite a large number of detection modes, it can still be highly beneficial to
      multiplex fewer modes.

PMID- 29216112
TI  - Real-time physical random bit generation at Gbps based on random fiber lasers.
AB  - We demonstrate for the first time, to the best of our knowledge, a high-speed
      physical random bit generator at gigabits/second without the time-delay signature
      based on chaotic power fluctuations of a random fiber laser. The random fiber
      laser is configured using a ring structure with semiconductor optical amplifiers
      as the optical gain and a fiber random grating as the random feedback medium. The
      long-length ring cavity provides a large number of densely spaced cavity modes
      that co-exist within the gain bandwidth tailored by the optical filter. Unlike
      fixed cavity modes in conventional fiber ring lasers, these modes are less phase
      correlated due to the random distributed feedback from the fiber random grating
      fabricated by a plane-by-plane inscription technique without phase control,
      leading to intensified lasing output fluctuations with high-dimensional chaotic
      dynamic natures without specific cavity features, when the random fiber laser is
      operated slightly above the lasing threshold. Random bit generation at a bit rate
      up to ~1.6  Gbps is achieved with verified randomness through standard tests.
      Different from the previously reported schemes requiring offline post-processing
      procedures, this physical random number generator can function in real time,
      offering high-quality randomness and security assurance for pertinent
      applications.

PMID- 29216113
TI  - Scaled model guidelines for solar coronagraphs' external occulters with an
      optimized shape.
AB  - One of the major challenges faced by externally occulted solar coronagraphs is
      the suppression of the light diffracted by the occulter edge. It is a
      contribution to the stray light that overwhelms the coronal signal on the focal
      plane and must be reduced by modifying the geometrical shape of the occulter.
      There is a rich literature, mostly experimental, on the appropriate choice of the
      most suitable shape. The problem arises when huge coronagraphs, such as those in
      formation flight, shall be tested in a laboratory. A recent contribution [Opt.
      Lett.41, 757 (2016)OPLEDP0146-959210.1364/OL.41.000757] provides the guidelines
      for scaling the geometry and replicate in the laboratory the flight diffraction
      pattern as produced by the whole solar disk and a flight occulter but leaves the
      conclusion on the occulter scale law somehow unjustified. This paper provides the
      numerical support for validating that conclusion and presents the first-ever
      simulation of the diffraction behind an occulter with an optimized shape along
      the optical axis with the solar disk as a source. This paper, together with Opt.
      Lett.41, 757 (2016)OPLEDP0146-959210.1364/OL.41.000757, aims at constituting a
      complete guide for scaling the coronagraphs' geometry.

PMID- 29216114
TI  - Packed Yagi-Uda nano-antennas using a unidirectional feed at visible wavelengths.
AB  - Optical nano-antennas' capability for controlling the intensity and direction of
      freely propagating waves is a precursor to demanding on-chip optical
      communications. Here we present a novel and efficiently packed Yagi-Uda (P-YU)
      nano-antenna which is dramatically directive and shortened. This is due to the
      excitation of a pair of strong interacting Au nanorods as a feed in the form of
      conventional Yagi-Uda (YU). Using a sophisticated feed with a unidirectional
      radiation pattern in a wavelength close to the antiphase hybridized plasmon
      causes significant directionality in the designed nano-antennas' emission. This
      allows us to reduce the number of directors or overall size while directivity and
      gain of the P-YU antenna considerably improve at about 610 nm.

PMID- 29216115
TI  - Efficient wavelength conversion with low operation power in a Ta2O5-based micro
      ring resonator.
AB  - The Ta2O5-based micro-ring resonator with an unloaded quality factor of 182,000
      has been demonstrated to realize efficient nonlinear wavelength generation. The
      propagation loss of the resonator is 0.5  cm-1, and the buildup factor of the
      ring resonator is estimated to be ~50. With a high buildup factor of the ring
      structure, the four-wave-mixing (FWM) conversion efficiency of -30  dB is
      achieved in the resonator with a pump power of 6 mW. Based on power-dependent FWM
      results, the nonlinear refractive index of Ta2O5 is estimated to be 1.4*10-14 
      cm2/W at a wavelength of ~1550  nm. The demonstration of an enhanced FWM process
      in the Ta2O5-based micro-ring cavity implies the possibility of realizing FWM
      based optical parametric oscillation in a Ta2O5-based micro-ring resonator.

PMID- 29216116
TI  - Terahertz spectrum splitting by a graphene-covered array of rectangular grooves.
AB  - We propose a bidirectional terahertz (THz) spectrum splitter using a practically
      simple metamaterial structure consisting of rectangular grooves covered by
      graphene. Thanks to the graphene optoelectronic tunability and by adjusting the
      grooves width, this structure provides nearly 2pi phase shift. At the same time,
      the reflection efficiency is acceptable throughout the phase shifts. We design
      each of the meta-atoms using a circuit model, and then we synthesize the final
      supercell based on the generalized Snell's law so that the structure reflects
      different frequency waves to totally different directions. The full-wave
      simulations demonstrate the beam splitting with a remarkable efficiency of around
      80%.

PMID- 29216117
TI  - Nanometer-scale luminescent thermometry in bovine embryos.
AB  - Luminescent nanothermometry is a powerful tool that can precisely monitor
      temperature changes in animal embryos. Among the most sensitive nanoluminescent
      temperature sensors are fluorescent nanodiamonds (FNDs), having nitrogen-vacancy
      color centers, and lanthanide-ion-doped upconversion nanoparticles (UCNPs). Here,
      we investigate their use as nanothermometers inside bovine embryos. The
      motivation for using both FNDs and UCNPs to measure temperature is to avoid the
      question of sensor confusion by the local cellular environment. Specifically, by
      simultaneously measuring temperature using two different modalities having
      different physics, it is possible to greatly improve the measurement confidence,
      thereby directly addressing the recent controversy surrounding temperature
      measurements in living organisms.

PMID- 29216118
TI  - Adaptive classifier allows enhanced flow contrast in OCT angiography using a
      histogram-based motion threshold and 3D Hessian analysis-based shape filtering.
AB  - In this Letter, we propose an adaptive digital classifier for flow contrast
      enhancement in optical coherence tomography angiography (OCTA). To solve the
      depth dependence in the initial motion-based classification, a depth-adaptive
      motion threshold was determined by performing a histogram analysis of an en-face
      image at each depth and identifying the static and dynamic voxel populations
      through fitting. In the follow-up shape-based classification, to adapt to the
      deformed vessel shapes in OCTA, a modified vesselness function along with an
      anisotropic Gaussian probe kernel was defined, and then a three-dimensional (3D)
      Hessian analysis-based shape filtering was utilized for effectively removing the
      residual static voxels. The experimental outcomes validated that the proposed
      adaptive digital classifier enabled a superior flow contrast by combining both
      the motion and 3D shape information.

PMID- 29216119
TI  - High-peak-power mode-locking pulse generation in a dual-loss-modulated laser with
      BP-SA and EOM.
AB  - In this Letter, a high-quality black phosphorus saturable absorber (BP-SA) with a
      multilayer structure was prepared, and its corresponding characteristics were
      investigated. Based on the BP-SA and an electro-optic modulator (EOM), a dual
      loss-modulated mode-locked laser with a controllable repetition rate and high
      peak power was realized, which has the repetition rate of EOM and the mode
      locking pulse width in the Q-switching and mode-locking laser. The output
      performances versus the pump power were measured. The maximum pulse peak power of
      3.89 MW was obtained with the minimum pulse duration of 119 ps. To the best of
      our knowledge, this is the highest pulse peak power with BP-SA reported.

PMID- 29216120
TI  - Cavity length matching and optical resonances in a Raman laser with the multimode
      pump source.
AB  - We report on the observation of local reduction in generation threshold and
      enhancement in the output energy of a nanosecond Raman laser when the round-trip
      time of its cavity is matched with that of a longitudinally multimode pump laser
      or related to the latter as a ratio of small integers. We refer both observations
      to the synchronous pump effect originating from the periodicity in the small
      scale intensity structure of the pump pulse.

PMID- 29216121
TI  - Surface nanoscale axial photonics at a capillary fiber: publisher's note.
AB  - This publisher's note corrects the surname of one of the authors of Opt. Lett.42,
      3060 (2017)OPLEDP0146-959210.1364/OL.42.003060.

PMID- 29216122
TI  - Delay line coherent pulse stacking.
AB  - Ultrafast fiber amplifiers are usually limited in terms of pulse energy and peak
      power due to fiber damage and nonlinearities. On the other hand, fiber amplifiers
      are very energy efficient. To take advantage of this efficiency, but still scale
      the pulse energy, coherent combining and pulse stacking have become the method of
      choice. Here we show how to directly and symmetrically stack up the pulses from
      an oscillator chain, using delay lines and phase preshaping of a 48 MHz, 1.5 MUm
      master oscillator. This method avoids the need for high-power low-loss dumpers as
      in passive stack and dump cavities and, compared to divided pulse amplification
      (DPA), it eliminates the need for splitting pulses and pulse picking and, thus,
      optimally utilizes the available seed power. Furthermore, it avoids the
      asymmetrical gain of the pulse bursts, which typically limits the efficiency in
      DPA.

PMID- 29216123
TI  - Variable-temperature variable-field magnetic circular photoluminescence (VTVH
      MCPL) spectroscopy for electronic-structure determination in nanoscale chemical
      systems.
AB  - In this Letter, we describe variable-temperature variable-field magnetic circular
      photoluminescence (VTVH-MCPL) spectroscopy as a complementary technique to
      absorption-based magnetic circular dichroism. A paramagnetic model system,
      Au25(SC8H9)18, is chosen to demonstrate the information content that is obtained
      from VTVH-MCPL. Specifically, the methods and analyses for the determination of
      electronic Lande g-factors, zero-field energy splittings, and relative A-, B-,
      and C-term contributions to the MCPL response are detailed. The determination of
      these system properties from photoluminescence data suggests the feasibility of
      point-source-based super-resolution magneto-optical microscopy.

PMID- 29216124
TI  - Phase-shifting digital holographic microscopy by using a multi-camera setup.
AB  - In this Letter, the use of two-coupled Mach-Zehnder interferometers for four pi/2
      phase shifting interferometry is introduced. A multi-camera arrangement using no
      more than beam splitters and mirrors is utilized to obtain in a single shot the
      needed phase-shifted interferograms in the different output channels of the
      setup. The simplicity of the setup makes it ideal for high-speed interferometry
      applications. This proposal is validated in digital holographic microscopy to
      visualize a biological sample of epidermal onion cells.

PMID- 29216125
TI  - Transfer of chirality from light to a Disperse Red 1 molecular glass surface.
AB  - Chiral structures and materials interact with light in well-documented ways, but
      light can also interact with achiral materials to generate chirality by
      inscribing its asymmetric configuration on photoresponsive materials, such as
      azobenzene derivatives. While it is thus possible to generate both two
      dimensional (2D) and three-dimensional (3D) chirality, 2D chirality is especially
      attractive because of its non-reciprocity. Herein, 2D chirality is induced on the
      surface of a glass-forming Disperse Red 1 derivative by irradiation with a single
      laser beam, yielding crossed spontaneous surface relief gratings with different
      pitches. Azimuth rotations up to 10 degrees  have been observed, and the absence
      of 3D chirality has been confirmed. This method thus allows generating non
      reciprocal planar chiral objects by a simple, single irradiation process on a
      thin film of a material that can easily be processed over large areas or onto
      small objects.

PMID- 29216126
TI  - Highly nonlinear yttrium-aluminosilicate optical fiber with a high intrinsic
      stimulated Brillouin scattering threshold.
AB  - Highly nonlinear (high-NA small-mode-area) optical fibers also possessing an
      intrinsically high stimulated Brillouin scattering threshold are described. More
      specifically, silica clad, yttrium-aluminosilicate core fibers are shown to
      exhibit an intrinsically low Brillouin gain coefficient between 0.125 and
      0.139*10-11  m/W and a Brillouin gain linewidth of up to 500 MHz. Losses on the
      order of 0.7 dB/m were measured, resulting from impurities in the precursor
      materials. Nonlinear refractive index values are determined to be similar to that
      of silica, but significant measurement uncertainty is attributed to the need to
      estimate dispersion curves since their direct measurement could not be made. The
      interest for highly nonlinear optical fibers with a low intrinsic Brillouin gain
      coefficient is expected to continue, especially with the growing developments of
      narrow-linewidth high-energy laser systems.

PMID- 29216127
TI  - Monolithic III-nitride photonic integration toward multifunctional devices.
AB  - The multiple functionalities of III-nitride semiconductors enable the integration
      with different components into a multicomponent system with enhanced functions.
      Here, we propose to fabricate and characterize a monolithic InGaN photonic
      circuit of a transmitter, waveguide, and receiver on an III-nitride-on-silicon
      platform. Both the transmitter and the receiver, sharing identical InGaN/GaN
      multiple-quantum-well structures and fabrication procedures, work to emit light
      and detect light independently. The 8 MUm wide and 200 MUm long InGaN waveguide
      couples the modulated light from the transmitter and sends the guided light to
      the receiver, leading to the formation of an in-plane light transmission system.
      The induced photocurrent at the receiver is highly sensitive to the light output
      of the transmitter. Multi-dimensional light transmissions are experimentally
      demonstrated at 200 Mb/s. These multifunctional photonic circuits open feasible
      approaches to the development of III-nitride multicomponent systems with
      integrated functions for comprehensive applications in the visible region.

PMID- 29216128
TI  - Experimental measurement of supercontinuum coherence in tellurite photonic
      crystal fibers.
AB  - Spectral and coherence evolutions were measured for supercontinuum (SC) generated
      in a 2.7 cm highly nonlinear tellurite photonic crystal fiber. Numerical
      simulations were performed based on the generalized nonlinear Schrodinger
      equation with noise. The measurements show that coherence degradation first
      occurs after soliton fission, and then spreads to longer wavelengths as the
      average power of the SC increases. The solitonic coherence shows much slower
      degradation than the overall coherence.

PMID- 29216129
TI  - Output power enhancement of a self-frequency-doubled laser by selective
      excitation of inequivalent active centers in La2CaB10O19 (Nd:LCB) crystal.
AB  - We demonstrated the output power enhancement of a self-frequency-doubled laser
      with Nd3+-doped lanthanum calcium borate La2CaB10O19 (Nd:LCB) crystals by
      selective excitation of its inequivalent active centers. When the Nd3+ ions
      located in the Ca2+ sites were excited in the Nd:LCB crystal, the fundamental
      laser at the wavelength of 1066 nm was successfully realized, which can keep the
      self-frequency-doubled wavelength away from the self-absorption peak of Nd3+ ions
      at about 523 nm. By optimizing the key parameters, the maximum output power of
      801 mW was achieved with the frequency-doubling at the wavelength of 533 nm, and
      the enhancement of output power was about 7.8 times compared with the results by
      excitation of Nd3+ ions in the La3+ sites. Up to now, this output power of the
      self-frequency-doubled laser represents the highest one in the Nd:LCB crystal,
      and the efficient emission at 533 nm should have promising applications in the
      visible range, such as laser displays, optical data storage, laser printing, etc.
      Meanwhile, the selective excitation of inequivalent active ions and the
      enhancement of the self-frequency-doubled laser may provide some inspiration for
      the investigation of multi-functional materials.

PMID- 29216130
TI  - Third-order nonlinearity OPO: Schmidt mode decomposition and tripartite
      entanglement.
AB  - We investigate quantum properties of light in optical parametric oscillators
      (OPOs) based on four-wave mixing gain in media with third-order nonlinearities.
      In spite of other competing chi(3) effects such as phase modulation, bipartite
      and tripartite entanglement is predicted above threshold. These findings are
      relevant for recent implementations of complementary metal-oxide-semiconductor
      (CMOS)-compatible on-chip OPOs.

PMID- 29216131
TI  - Controllable symmetric and asymmetric spin splitting of Laguerre-Gaussian beams
      assisted by surface plasmon resonance.
AB  - The spin splitting of light beams carrying orbital angular momentum (OAM) is
      investigated theoretically in attenuated internal reflection in the Kretschmann
      configuration. The excitation of the surface plasmon resonance (SPR) can
      significantly enhance the OAM-induced Imbert-Fedorov (IF) shift and the OAM
      dependent spin splitting. The cooperation effect of these two shifts will result
      in an asymmetric spin splitting, which varies with the incident angle and
      polarization state. Specially, at the SPR angle, the OAM-induced IF shift
      vanishes, and the OAM-dependent spin splitting will cause a symmetric spin
      splitting. However, when the incident beam is horizontally polarized, the OAM
      induced IF shift predominates. Thus the two spin components of the reflected will
      not be split; instead, they will be shifted together. This flexible control of
      the optical spin splitting can find applications in quantum information and
      precision metrology.

PMID- 29216132
TI  - Extinction by a homogeneous spherical particle in an absorbing medium.
AB  - We use a recent computer implementation of the first-principles theory of
      electromagnetic scattering to compute far-field extinction by a spherical
      particle embedded in an absorbing unbounded host. Our results show that the
      suppressing effect of increasing absorption inside the host medium on the ripple
      structure of the extinction efficiency factor as a function of the size parameter
      is similar to the well-known effect of increasing absorption inside a particle
      embedded in a nonabsorbing host. However, the accompanying effects on the
      interference structure of the extinction efficiency curves are diametrically
      opposite. As a result, sufficiently large absorption inside the host medium can
      cause negative particulate extinction. We offer a simple physical explanation of
      the phenomenon of negative extinction consistent with the interpretation of the
      interference structure as being the result of interference of the field
      transmitted by the particle and the diffracted field due to an incomplete
      wavefront resulting from the blockage of the incident plane wave by the
      particle's geometrical projection.

PMID- 29216133
TI  - Broadband mode switch based on a three-dimensional waveguide Mach-Zehnder
      interferometer.
AB  - We propose a mode switch that operates on modulating the optical phases of a
      three-dimensional balanced four-arm waveguide Mach-Zehnder interferometer. We
      design and fabricate the device with polymer material to achieve thermo-optic
      switching between any two of the E11, E21, E12, and E22 modes of the waveguide.
      Our experimental device shows an extinction ratio higher than 14 dB and a
      switching time shorter than 3.7 ms, measured with the E11 mode switched to any of
      the other modes at 1550 nm. This mode switch can operate over a wide range of
      wavelengths with weak polarization dependence and could be used in reconfigurable
      fiber-based mode-division-multiplexing systems where mode routing is required.

PMID- 29216134
TI  - Spatially multiplexed orbital-angular-momentum-encoded single photon and
      classical channels in a free-space optical communication link.
AB  - We experimentally demonstrate spatial multiplexing of an orbital angular momentum
      (OAM)-encoded quantum channel and a classical Gaussian beam with a different
      wavelength and orthogonal polarization. Data rates as large as 100 MHz are
      achieved by encoding on two different OAM states by employing a combination of
      independently modulated laser diodes and helical phase holograms. The influence
      of OAM mode spacing, encoding bandwidth, and interference from the co-propagating
      Gaussian beam on registered photon count rates and quantum bit error rates is
      investigated. Our results show that the deleterious effects of intermodal
      crosstalk effects on system performance become less important for OAM mode
      spacing Delta>=2 (corresponding to a crosstalk value of less than -18.5  dB). The
      use of OAM domain can additionally offer at least 10.4 dB isolation besides that
      provided by wavelength and polarization, leading to a further suppression of
      interference from the classical channel.

PMID- 29216135
TI  - Improved lateral resolution with an annular vortex depletion beam in STED
      microscopy.
AB  - We report on the experimental demonstration of improved lateral resolution in
      stimulated emission depletion (STED) microscopy using an annular depletion beam
      configuration. A tight and finely tuned doughnut focal spot can be created by
      annular vortex illumination. Its application in STED microscopy for enhanced
      lateral resolution is systematically investigated by imaging 40 nm fluorescent
      beads. An improved resolution with more than 20% reduced effective point spread
      function of the imaging system determined by the full width at half-maximum
      compared to that of the conventional STED is achieved. The proposed scheme also
      demonstrates its resolving capability for biological samples. The principle holds
      great potential in the research fields of biological superresolution imaging as
      well as STED-based nanolithography and high-density optical data storage.

PMID- 29216136
TI  - Giant self-induced transparency of intense few-cycle terahertz pulses in n-doped
      silicon.
AB  - The results of high-field terahertz transmission experiments on n-doped silicon
      (carrier concentration of 8.7*1016  cm-3) are presented. We use terahertz pulses
      with electric field strengths up to 3.1  MV cm-1 and a pulse duration of 700 fs.
      A huge transmittance enhancement of ~90 times is observed with increasing of the
      terahertz electric field strengths within the range of 1.5-3.1  MV cm-1.

PMID- 29216137
TI  - Generation of 70-fs pulses at 2.86  MUm from a mid-infrared fiber laser.
AB  - We propose and demonstrate a simple route to few-optical-cycle pulse generation
      from a mid-infrared fiber laser through nonlinear compression of pulses from a
      holmium-doped fiber oscillator using a short length of chalcogenide fiber and a
      grating pair. Pulses from the oscillator with 265-fs duration at 2.86 MUm are
      spectrally broadened through self-phase modulation in step-index As2S3 fiber to
      141-nm bandwidth and then re-compressed to 70 fs (7.3 optical cycles). These are
      the shortest pulses from a mid-infrared fiber system to date, and we note that
      our system is compact, robust, and uses only commercially available components.
      The scalability of this approach is also discussed, supported by numerical
      modeling.

PMID- 29216138
TI  - Discovery of high-gain stimulated polariton scattering near 4  THz from lithium
      niobate.
AB  - Lithium niobate is the most popular material for terahertz wave generation via
      stimulated polariton scattering (SPS), previously known to have a gain peak near
      2 THz. Here we report the discovery of another phase-matched gain peak near 4 THz
      in lithium niobate, which greatly extends the useful gain spectrum of lithium
      niobate. Despite the relatively high 4 THz absorption in lithium niobate, the 4
      THz SPS becomes dominant over the 2 THz one in an intensely pumped short lithium
      niobate crystal due to less diffraction-induced absorption and mode-area
      mismatch. We also demonstrate a signal-seeded OTPO that generates 1.4 nJ at 4.2
      THz from lithium niobate with 17.5 mJ pump energy.

PMID- 29216139
TI  - Integrated broadband Ce:YIG/Si Mach-Zehnder optical isolators with over 100  nm
      tuning range.
AB  - We demonstrate integrated optical isolators with broadband behavior for the
      standard silicon-on-insulator platform. We achieve over 20 dB of optical
      isolation across 18 nm of optical bandwidth. The isolator is completely
      electrically controlled and does not require a permanent magnet. Furthermore, we
      demonstrate the ability to tune the central operating wavelength of the isolator
      across 100 nm, which covers the entire S + C telecom bands. These devices show
      promise for integration in optical systems in which broadband isolation is needed
      such as wavelength multiplexed systems or optical sensors.

PMID- 29216140
TI  - Modified calculation method of relative sensitivity for fluorescence intensity
      ratio thermometry.
AB  - The calculation method of relative sensitivity (Sr) for fluorescence intensity
      ratio (FIR) thermometry is discussed, taking the F33-H63 and H43-H63 transitions
      of Tm3+ as examples. The value of Sr is calculated using its original definition,
      and is found to largely deviate from the result obtained using the conventional
      method that is widely used at present. This deviation is found to stem from the
      neglect of an offset. A modified expression of Sr is proposed, which shows the
      true performance of FIR technology and makes it possible to precisely compare the
      Sr values obtained using various methods.

PMID- 29216141
TI  - Subharmonic anti-phase dynamics in coupled mode-locked semiconductor lasers.
AB  - We show that coupled mode-locked semiconductor lasers can operate in a
      subharmonic regime in which the two lasers pulsate in an anti-phase manner at one
      half the fundamental mode-locking frequency of the solitary lasers. In the
      subharmonic mode, each pulse has almost twice the energy carried by the isolated
      lasers in the fundamental mode-locked regime and is also significantly shorter in
      duration. Depending on the unsaturated gain and coupling strength, the lasers can
      also exhibit bistability, perfect synchronization, and delayed synchronization,
      as well as three-halves and five-halves harmonic mode locking. The observed
      behaviors are robust and persist in the presence of noise.

PMID- 29216142
TI  - Realization of a complementary medium using dielectric photonic crystals.
AB  - By exploiting the scaling invariance of photonic band diagrams, a complementary
      photonic crystal slab structure is realized by stacking two uniformly scaled
      double-zero-index dielectric photonic crystal slabs together. The space
      cancellation effect in complementary photonic crystals is demonstrated in both
      numerical simulations and microwave experiments. The refractive index dispersion
      of double-zero-index dielectric photonic crystal is experimentally measured.
      Using pure dielectrics, our photonic crystal structure will be an ideal platform
      to explore various intriguing properties related to a complementary medium.

PMID- 29216143
TI  - Ultra-compact waveguide crossing for a mode-division multiplexing optical
      network.
AB  - We propose and experimentally demonstrate an ultra-compact multimode waveguide
      crossing that can process two modes simultaneously. The symmetric Y-junction is
      introduced to split the high-order modes into fundamental ones, easing the
      subsequent processing. The footprint of the proposed crossing is as compact as 21
      MUm*21  MUm. The measured results show an insertion loss of ~1.82  dB for the
      TE0 mode and ~0.46  dB for the TE1 mode at 1550 nm, as well as a crosstalk of <
      18  dB from 1510 to 1600 nm.

PMID- 29216144
TI  - Robust terahertz polarizers with high transmittance at selected frequencies
      through Si wafer bonding technologies.
AB  - Terahertz (THz) polarizers with robust structure and high transmittance are
      demonstrated using 3D-integrated circuit (IC) technologies. A Cu wire-grid
      polarizer is sealed and well protected by Si-bonded wafers through a low
      temperature eutectic bonding method. Deep reactive-ion etching is used to
      fabricate the anti-reflection (AR) layers on outward surfaces of bonded wafers.
      The extinction ratio and transmittance of polarizers are between 20 dB and 33 dB,
      and 13 dB and 27 dB for 10 MUm and 20 MUm pitch wire-grids, respectively, and
      100% at central frequency, depending on frequency and AR layer thickness. The
      process of polarizer fabrication is simple from mature semiconductor
      manufacturing techniques that lead to high yield, low cost, and potential for THz
      applications.

PMID- 29216145
TI  - Tailoring axial intensity of laser beams with a heart-shaped hole.
AB  - We demonstrated a simple heart-shaped hole to tailor the axial intensity of a
      collimated laser beam. This hole is transformed from a soft-boundary one, which
      avoids the difficulty in fabricating the soft-boundary mask designed by the
      apodization method, as well as the interference problem caused by the pixel
      structure of the spatial light modulator. When a collimated light passes through
      this hole, its axial intensity oscillates less than 11% within a certain
      distance, while the fluctuation after the circular aperture is up to 200%. We
      compared the propagation of beams after this hole and a circular aperture
      experimentally and theoretically. The results show that this hole is a useful
      tool to get the laser beam with uniform axial intensity.

PMID- 29216146
TI  - In situ laser measurement of oxygen concentration and flue gas temperature
      utilizing chemical reaction kinetics.
AB  - Combustion research requires detailed localized information on the dynamic
      combustion conditions to improve the accuracy of the simulations and, hence,
      improve the performance of the combustion processes. We have applied chemical
      reaction kinetics of potassium to measure the local temperature and O2
      concentration in flue gas. An excess of free atomic potassium is created in the
      measurement volume by a photofragmenting precursor molecule such as potassium
      chloride or KOH which are widely released from solid fuels. The decay of the
      induced potassium concentration is followed with an absorption measurement using
      a narrow-linewidth diode laser. The temperature and O2 concentration are solved
      from the decay curve features using equations obtained from calibration
      measurements in a temperature range of 800 degrees C-1000 degrees C and in O2
      concentrations of 0.1%-21%. The local flue gas temperature and O2 concentration
      were recorded in real time during devolatilization, char burning, and ash cooking
      phases of combustion in a single-particle reactor with a 5 Hz repetition rate.
      The method can be further extended to other target species and applications where
      the chemical dynamics can be disturbed with photofragmentation.

PMID- 29216148
TI  - Temporal spectrum of beam wander for Gaussian Schell-model beams propagating in
      atmospheric turbulence with finite outer scale: publisher's note.
AB  - This publisher's note corrects a typo in the title in Opt. Lett.38, 1887
      (2013)OPLEDP0146-959210.1364/OL.38.001887.

PMID- 29216147
TI  - Wide-field interferometric measurement of a nonstationary complex coherence
      function.
AB  - Spatial coherence function (SCF) is a complex function of two spatial coordinates
      that, in general, carries more information than the bare intensity distribution.
      A fast and quantitatively accurate measurement of the SCF is extremely important
      for a range of applications in optical sensing and imaging. Here, we demonstrate
      an efficient two-step procedure for measuring the full-field complex coherence
      function. The measurement relies on an optimized design of a wavefront shearing
      interferometer capable of characterizing spatially inhomogeneous fields over an
      extended angular domain. The measurement precision is confirmed by the excellent
      agreement with a numerical estimation based on Fresnel calculations. We
      demonstrate that the sensitivity and the measurement range afforded by our
      instrument permits us to reliably describe the differences in the complex
      coherence functions that are due to subtle modifications in the shape, position,
      and orientation of radiation sources.

PMID- 29216149
TI  - On-chip wavelength locking for photonic switches.
AB  - We present an on-chip wavelength reference with a partial drop ring resonator and
      germanium photodetector. This approach can be used in ring-resonator-based
      wavelength-selective switches where absolute wavelength alignment is required. We
      use the temperature dependence of heater resistance as a temperature sensor.
      Additionally, we discuss locking speed, statistical variation of heater
      resistances, and tuning speed of the switches.

PMID- 29216151
TI  - Asynchronous and synchronous dual-wavelength pulse generation in a passively mode
      locked fiber laser with a mode-locker.
AB  - The evolution from asynchronous to synchronous dual-wavelength pulse generation
      in a passively mode-locked fiber laser is experimentally investigated by
      tailoring the intracavity dispersion. Through tuning the intracavity-loss
      dependent gain profile and the birefringence-induced filter effect, asynchronous
      dual-wavelength soliton pulses can be generated until the intracavity anomalous
      dispersion is reduced to ~8  fs/nm. The transition from asynchronous to
      synchronous pulse generation is then observed at an elevated pump power in the
      presence of residual anomalous dispersion, and it is shown that pulses are
      temporally synchronized at the mode-locker in the cavity. Spectral sidelobes are
      observed and could be attributed to the four-wave-mixing effect between dual
      wavelength pulses at the carbon nanotube mode-locker. These results could provide
      further insight into the design and realization of such dual-wavelength ultrafast
      lasers for different applications such as dual-comb metrology as well as better
      understanding of the inter-pulse interactions in such dual-comb lasers.

PMID- 29216150
TI  - Two-dimensional microbend sensor based on long-period fiber gratings in an
      isosceles triangle arrangement three-core fiber.
AB  - To realize the 2D microbend sensor, we design and fabricate two non-orthogonal
      long-period fiber gratings (LPFGs) in an isosceles triangle arrangement three
      core optical fiber which is made in our lab, making an isosceles triangle
      arrangement three-core optical fiber. To mark two directions without crosstalk,
      we write two different periods of LPFG in each of the two external cores and the
      central core, which induces a strong asymmetric refractive index arrangement in
      the fiber cross section. Theoretical analysis and experimental results verify
      that the resonant wavelength originates from the tunneling between the LP01 core
      mode in the center core and the external core. In the confirmation experiments,
      the proposed sensor can distinguish multiple bending directions and experiences a
      maximum sensitivity of 3.234  nm/m-1 with a bending range of 0-0.588  m-1.

PMID- 29216152
TI  - Noninvasive characterization of optical fibers.
AB  - Capillary optical fibers with hole diameters of several micrometers are important
      for novel plasmonic applications and medical diagnosis. In order to ensure the
      optical functionality of these fibers, the diameter of the capillary hole needs
      to be realized with high accuracy. Here, we introduce a novel and noninvasive
      methodology to characterize optical fibers and discuss it for the assessment of
      capillaries. In this method, the fiber is side-illuminated by a coherent beam,
      and the resulting diffraction pattern is analyzed. This corresponds to an in-line
      holographic measurement in the presence of strong scattering. A numerical
      parameter retrieval allows us to characterize the capillary hole diameter with an
      accuracy of approximately 100 nm for radii between several hundreds of nanometers
      and several tens of micrometers.

PMID- 29216153
TI  - Cr3+-doped Bi2Ga4O9-Bi2Al4O9 solid-solution phosphors: crystal-field modulation
      and lifetime-based temperature sensing.
AB  - Cr3+-doped Bi2Ga4O9-Bi2Al4O9 solid-solution (SS) phosphors were fabricated to
      explore their possible application in fluorescence lifetime-based temperature
      sensing. The present samples exhibited E2->A24 R-line emissions associated with
      T24->A24 phonon sideband emissions of Cr3+ in the wavelength range of 600-850 nm
      upon the excitation of visible light. Through modifying the Al/Ga ratio in the SS
      hosts, the Cr3+ crystal field was easily tuned from intermediate to strong, being
      beneficial to modulate an energy gap between E2 and T24 thermally coupled
      emitting states. As a result, linearly temperature-sensitive fluorescence
      lifetime was achieved in the Cr3+-doped Bi2Ga4O9-Bi2Al4O9 SSs with a high Al/Ga
      ratio, enabling us to conveniently and accurately determine a temperature with a
      high relative sensitivity of 2.13-3.26%  K-1.

PMID- 29216154
TI  - Calibrated phase-shifting digital holography based on a dual-camera system.
AB  - A calibrated phase-shifting digital holography system based on the sampling Moire
      technique is proposed. Two synchronized cameras are used in this system. One is
      to record the conventional holograms that include the object information, and the
      other is to record the interference fringes to analyze phase-shifting errors. An
      algorithm for improving the quality of the reconstructed images is proposed. In
      this Letter, the effectiveness of the proposed system and algorithm is
      demonstrated in four-step phase-shifting digital holography. The quality of the
      reconstructed images is greatly improved from both the numerical simulation and
      experiment.

PMID- 29216155
TI  - Linear autocorrelation of partially coherent extreme-ultraviolet lasers: a
      quantitative analysis.
AB  - A quantitative interpretation method is described for experiments involving the
      linear autocorrelation of partially coherent extreme-ultraviolet (XUV) pulses,
      generated by either x-ray free-electron lasers or plasma-based XUV lasers. A
      recently published modeling method for partially coherent pulses is numerically
      implemented in that specific case. Analytical expressions for the statistical
      root-mean-square average of the fringe visibility are derived. The method yields
      unambiguous information on both the coherence time and the pulse duration,
      providing a valuable data interpretation tool.

PMID- 29216156
TI  - Butterfly-inspired micro-concavity array film for color conversion efficiency
      improvement of quantum-dot-based light-emitting diodes.
AB  - Inspired by the Papilio blumei butterfly, quantum-dot (QD) film coupled with
      micro-concavity array (MCA) films is proposed in this Letter to enhance color
      conversion efficiency (CCE) of QD-based light-emitting diodes (LEDs). The
      diameter, aspect ratio, and pitch of the MCA are optimized in the optical
      simulations. Both the simulation and experimental results show that the
      scattering and double reflection effects are the key to the CCE improvement of QD
      films. The results show that the CCEs are increased from 19.98% to 21.59% and
      21.78% (350 mA) for single-sided microstructured QD film and double-sided
      microstructured QD film configurations, respectively. Overall, the MCA film is a
      promising solution to enhance the CCE of QD-based LEDs.

PMID- 29216158
TI  - Three-dimensional patterned graphene oxide-quantum dot microstructures via two
      photon crosslinking.
AB  - The two-photon crosslinking of graphene oxide-quantum dots (GOQDs) adopts rose
      Bengal as the photoactivator to induce the GOQD assembly process. Based on the
      Forster resonance energy transfer mechanism with oxygen as the crosslinking
      medium, three-dimensional patterned GOQD microstructures with near diffraction
      limit spatial resolution have been fabricated and analyzed by a multiphoton
      excited fabrication instrument/microscope.

PMID- 29216159
TI  - Cross-correlation photothermal optical coherence tomography with high effective
      resolution.
AB  - We developed a cross-correlation photothermal optical coherence tomography (CC
      PTOCT) system for photothermal imaging with high lateral and axial resolution.
      The CC-PTOCT system consists of a phase-sensitive OCT system, a modulated pumping
      laser, and a digital cross-correlator. The pumping laser was used to induce the
      photothermal effect in the sample, causing a slight phase modulation of the OCT
      signals. A spatial phase differentiation method was employed to reduce phase
      accumulation. The noise brought by the phase differentiation method and the
      strong background noise were suppressed efficiently by the cross-correlator,
      which was utilized to extract the photothermal signals from the modulated
      signals. Combining the cross-correlation technique with spatial phase
      differentiation can improve both lateral and axial resolution of the PTOCT
      imaging system. Clear photothermal images of blood capillaries of a mouse ear in
      vivo were successfully obtained with high lateral and axial resolution. The
      experimental results demonstrated that this system can enhance the effective
      transverse resolution, effective depth resolution, and contrast of the PTOCT
      image effectively, aiding the ongoing development of the accurate 3D functional
      imaging.

PMID- 29216161
TI  - Analytical registration of vertical image drifts in parallel beam tomographic
      data.
AB  - Reconstructing tomographic images of high resolution, as in x-ray microscopy or
      transmission electron microscopy, is often limited by the stability of the stages
      or sample drifts, which requires an image alignment prior to reconstruction.
      Feature-based image registration is routinely used to align images, but this
      technique relies on strong features in the sample or the application of gold
      tracer particles, for example. In this Letter, we present an analytic approach
      for achieving the vertical registration based on the inherent properties of the
      data acquired for tomographic reconstruction. It is computationally cheap to
      implement and can be easily integrated into existing reconstruction pipelines.

PMID- 29216160
TI  - Broadband rotary joint for high-speed ultrahigh-resolution endoscopic OCT imaging
      at 800  nm.
AB  - We report the development of a broadband rotary joint for high-speed ultrahigh
      resolution endoscopic optical coherence tomography (OCT) imaging in the 800 nm
      spectral range. This rotary joint features a pair of achromatic doublets in order
      to achieve broadband operation for a 3 dB bandwidth over 150 nm. The measured one
      way throughput of the rotary joint is greater than 80%, while the fluctuation of
      the double-pass coupling efficiency during 360 deg rotation is less than +/-5% at
      a near video-rate speed of 20 revolutions/s (rps). The rotary joint is used in
      conjunction with a diffractive-optics-based endoscope and 800 nm spectral domain
      OCT system and achieved an ultrahigh axial resolution of ~2.4  MUm in air. The
      imaging performance is demonstrated by 3D circumferential imaging of a mouse
      colon in vivo.

PMID- 29216162
TI  - Experimental demonstration of a single silicon ring resonator with an ultra-wide
      FSR and tuning range.
AB  - We present an experimental realization of a pseudo single-mode silicon ring
      resonator with an ultra-wide free spectral range and tuning range. The device is
      a single microring resonator with a tunable reflector integrated inside. The
      reflector is designed to have zero reflection for only one resonance of the ring,
      while all other resonances will suffer strong reflection. Given that the
      reflection inside a ring resonator leads to resonance splitting and degradation
      of the extinction ratio (ER), we obtain a ring resonator where only a single
      resonance has a large ER, while all others have a very low ER. The large ER
      resonance can be continuously tuned using metal heaters to achieve a broad tuning
      range over 55 nm with 16 mW of power injected into the phase shifter.

PMID- 29216157
TI  - Optical image cloning based on electromagnetic induced absorption.
AB  - We investigate, both theoretically and experimentally, optical image cloning via
      electromagnetic induced absorption (EIA). We demonstrate the transfer of small 2D
      real images imprinted onto a strong coupling beam to a weak probe beam in a Rb
      vapor cell. We show through EIA that the coupling beam's image is cloned beyond
      the usual diffraction, with a potential improvement in spatial resolution of the
      cloned image by a factor of three in comparison to that of the original coupling
      beam. Optical cloning through EIA is based on position selective nonlinear
      absorption, and it does not rely on spatial modulation of the refractive index.

PMID- 29216163
TI  - Fan-beam steering device using a photonic crystal slow-light waveguide with
      surface diffraction grating.
AB  - Compact non-mechanical beam steering devices are desired not only for current
      common applications, but also for advanced applications such as light detection
      and ranging. We use a Si photonic crystal slow-light waveguide with a diffraction
      grating, which radiates the guided mode to free space and steers a fan beam by
      sweeping the wavelength. Due to its large angular dispersion, slow light enhances
      the steering range without degrading the beam quality, resulting in more
      resolution points. We fabricated 600 MUm devices and observed a 23 degrees 
      steering range and a beam divergence of 0.23 degrees , which resulted in 100
      resolution points.

PMID- 29216164
TI  - Focusing light through dynamical samples using fast continuous wavefront
      optimization.
AB  - We describe a fast continuous optimization wavefront shaping system able to focus
      light through dynamic scattering media. A micro-electro-mechanical system-based
      spatial light modulator, a fast photodetector, and field programmable gate array
      electronics are combined to implement a continuous optimization of a wavefront
      with a single-mode optimization rate of 4.1 kHz. The system performances are
      demonstrated by focusing light through colloidal solutions of TiO2 particles in
      glycerol with tunable temporal stability.

PMID- 29216166
TI  - Femtosecond laser-pumped plasmonically enhanced near-infrared random laser based
      on engineered scatterers.
AB  - In this Letter, we report on the design, fabrication, and implementation of a
      novel plasmon-mode-driven low-threshold near-infrared (NIR) random laser (RL) in
      the 850-900 nm range based on plasmonic ZnS@Au core-shell scatterers. Plasmon
      modes in the NIR region are used for nanoscale scatterer engineering of ZnS@Au
      core-shell particles to enhance scattering, as against pristine ZnS. This
      plasmonic scattering enhancement coupled with femtosecond (fs) laser pumping is
      shown to cause a three-fold lasing threshold reduction from 325  MUJ/cm2 to 100 
      MUJ/cm2 and a mode Q-factor enhancement from 200 to 540 for ZnS@Au-based RL, as
      compared to pristine ZnS-based RL. Local field enhancement due to plasmonic
      ZnS@Au scatterers, as evidenced in the finite-difference time-domain simulation,
      further adds to this enhancement. This work demonstrates a novel scheme of
      plasmonic mode coupling in the NIR region and fs excitation in a random laser
      photonic system, overcoming the inherent deficiencies of weak absorption of gain
      media and poor scattering cross sections of dielectric scatterers for random
      lasing in the NIR spectrum.

PMID- 29216167
TI  - Time reflection and refraction of graphene plasmons at a temporal discontinuity.
AB  - A dynamical change of material properties induces a special type of reflection
      and refraction at a temporal discontinuity. Here, we study the interaction of
      graphene plasmons with single and double temporal discontinuities or shocks,
      leading to controlled in-plane scattering. We analytically determine the Fresnel
      like coefficients for graphene plasmons at these boundaries, and validate our
      results by rigorous numerical simulations. Temporally controlled doping of two
      dimensional materials such as graphene thus leads to a new mechanism for planar
      and compact plasmonic devices.

PMID- 29216165
TI  - Doubly positive functions in coherent and partially coherent optics.
AB  - A function is said to be doubly positive if it is everywhere non-negative and the
      same holds true for its Fourier transform. After discussing applications to
      coherent and partially coherent fields, we present examples and properties of
      such functions together with procedures to devise classes of them.

PMID- 29216168
TI  - Two-dimensional tunable orbital angular momentum generation using a vortex fiber.
AB  - We demonstrate the two-dimensional tunable orbital angular momentum (OAM)
      generation in a ring-core (vortex) fiber. The LP11 mode generated by an all fiber
      fused coupler is coupled into a vortex fiber. Because the vector modes of the
      LP11 mode group in the vortex fiber are no longer degenerate, the mode status
      will change between linearly polarized modes (LPMs) and complex OAM modes
      periodically during propagation. The generated OAM can be tuned smoothly by
      filtering the mixed mode with different polarization directions or changing the
      wavelength at a certain polarization directions. The two-dimensional tuning of
      OAM from l=-1 to l=+1 is experimentally demonstrated in an all fiber OAM
      generator.

PMID- 29216170
TI  - Zero-orbital-angular-momentum laser printing of chiral nanoneedles.
AB  - Laser irradiation of various materials including metals, polymers, and
      semiconductors with vortex beams was previously shown to "twist" transiently
      molten matter providing the direct easy-to-implement way to obtain chiral surface
      relief. Specifically for metals, this effect was attributed to transfer of an
      orbital angular momentum (OAM) carried by a vortex beam. In this Letter, we
      report the formation of twisted metallic nanoneedles on surfaces of silver and
      gold films under their irradiation by a zero-OAM laser beam with a spiral-shaped
      intensity distribution. Our comparative experiments clearly demonstrate, for the
      first time to the best of our knowledge, that the formation of the chiral
      nanoneedles on the noble-metal films is mainly governed by the temperature
      gradient-induced chiral thermocapillary mass transfer, rather than by OAM-driven
      rotation of the molten matter.

PMID- 29216169
TI  - Nonlinear optical susceptibility of two-dimensional WS2 measured by hyper
      Rayleigh scattering.
AB  - Hyper Rayleigh scattering (HRS) was used to measure the second-order nonlinear
      susceptibility, chi(2), for liquid exfoliated WS2 monolayers. To the best of our
      knowledge, it is the first reported application of the HRS technique to assess
      the bulk-like chi(2) of a two-dimensional (2D) material. The concentration
      dependent HRS signal indicated a 4.90+/-0.30*10-25  esu first hyperpolarizability
      for 42 nm WS2 monolayers under 1064 nm laser irradiation using para-nitroaniline
      as an external reference. The corresponding value of chixxx(2) was calculated to
      be 460+/-28  pm V-1. This was within 46% of independent density functional theory
      predictions. Agreement with theory was improved over related microscopy-based
      approaches. These results support the use of HRS to evaluate 2D materials for
      nonlinear frequency mixing applications.

PMID- 29216172
TI  - Enhancement of bulk second-harmonic generation from silicon nitride films by
      material composition.
AB  - We present a comprehensive tensorial characterization of second-harmonic
      generation from silicon nitride films with varying compositions. The samples were
      fabricated using plasma-enhanced chemical vapor deposition, and the material
      composition was varied by the reactive gas mixture in the process. We found a six
      fold enhancement between the lowest and highest second-order susceptibility, with
      the highest value of approximately 5 pm/V from the most silicon-rich sample.
      Moreover, the optical losses were found to be sufficiently small (below 6 dB/cm)
      for applications. The tensorial results show that all samples retain in-plane
      isotropy independent of the silicon content, highlighting the controllability of
      the fabrication process.

PMID- 29216171
TI  - On Babinet's principle and diffraction associated with an arbitrary particle.
AB  - Babinet's principle is widely used to compute the diffraction by a particle.
      However, the diffraction by a 3-D object is not totally the same as that
      simulated with Babinet's principle. This Letter uses a surface integral equation
      to exactly formulate the diffraction by an arbitrary particle and illustrate the
      condition for the applicability of Babinet's principle. The present results may
      serve to close the debate on the diffraction formalism.

PMID- 29216173
TI  - Photonics-based multi-function analog signal processor based on a polarization
      division multiplexing Mach-Zehnder modulator.
AB  - A photonics-based multi-function analog signal processor based on an optical
      polarization division multiplexing dual-parallel Mach-Zehnder modulator is
      proposed and demonstrated, which can implement simultaneously photonic microwave
      phase shifting, upconversion/downconversion and filtering with excellent
      tunability. An experiment is carried out. Downconverted and upconverted phase
      shifters with phases continuously tuned from -180 to 180 deg over 0-11 and 11-33
      GHz are implemented. Based on the frequency-mixed phase shifter, a four-tap
      microwave photonic filter that has the capability to select a frequency-mixed
      component is built. The proposed approach features multi-function, scalable
      independent channels, a wide bandwidth, and high tunability, which can find
      applications in beamforming networks, radio frequency frontends, and radio over
      fiber systems.

PMID- 29216174
TI  - Spatiotemporal diffraction-free pulsed beams in free-space of the Airy and Bessel
      type.
AB  - We investigate the dynamics of spatiotemporal optical waves with one transverse
      dimension obtained as the intersections of the dispersion cone with a plane. We
      show that, by appropriate spectral excitations, the three different types of
      conic sections (elliptic, parabolic, and hyperbolic) can lead to optical waves of
      the Bessel, Airy, and modified Bessel types, respectively. We find closed form
      solutions that accurately describe the wave dynamics and unveil their fundamental
      properties.

PMID- 29216175
TI  - Fiber-optic radio frequency transfer based on active phase noise compensation
      using a carrier suppressed double-sideband signal.
AB  - In this Letter, we propose a fiber-optic radio frequency (RF) transfer based on
      active phase noise compensation adopting a carrier suppressed double-sideband
      (CSDSB) signal. The forward CSDSB signal is generated based on the transmitted RF
      signal at the local site to discriminate from the backward RF signal. The forward
      and backward signals are transmitted over the same fiber with the same wavelength
      to guarantee the bidirectional propagation symmetry. The impact of backscattering
      is efficiently suppressed by electrical filtering at the sites. A 1 GHz signal
      transfer over a 40 km optical link is performed in a laboratory. The results show
      that the proposed scheme can improve the short-term stability from 1.9  e-13/s to
      3.9  e-14/s in contrast to the scheme with backscattering while reaching a long
      term stability of 2.0  e-16/10000 s.

PMID- 29216176
TI  - Reducing light scattering in high-reflection coatings through destructive
      interference at fully correlated interfaces.
AB  - Light scattering in quarter-wave high-reflection (QWHR) coatings with fully
      correlated interfaces was reduced by adding Fabry-Perot (FP) cavity structures on
      top of the multilayer. The properly designed FP cavity can induce destructive
      interference for fully correlated interfaces and reduce the scattering loss.
      Compared to QWHR coatings, adding one FP cavity could decrease the scattering at
      the near specular angles, and two FP cavities have the potential to reduce light
      scattering in a broad angular range. A low-scattering HR (LSHR) coating using two
      FP cavities has been realized to suppress light scattering. The numerical
      scattering calculation illustrated that the total scattering loss of the LSHR was
      about 30% less than that of the QWHR coatings. The measured angle-resolved
      scattering of the LSHR coating showed a good correspondence to the numerical
      calculation, although a small deviation exists in a limited angular range.

PMID- 29216177
TI  - Generation of uniformly oriented in-plane magnetization with near-unity purity in
      4pi microscopy.
AB  - In this Letter, we numerically demonstrate the all-optical generation of
      uniformly oriented in-plane magnetization with near-unity purity (more than 99%)
      under a 4pi microscopic configuration. This is achieved through focusing two
      counter-propagating vector beams consisting of coherently configured linear and
      radial components. Based on the Debye diffraction theory, constructive and
      destructive interferences of the focal field components can be tailored under the
      4pi configuration to generate high-purity uniformly polarized transverse and
      longitudinal electric-field components in the center of the focal region.
      Consequently, near-unity purity in-plane magnetization with a uniform orientation
      within the focal volume defined by the full width at half-maximum can be created
      through the inverse Faraday effect. In addition, it reveals that the purity of
      the in-plane magnetization is robust against the numerical aperture of the focal
      lens. This result expands the flexibility of magnetization manipulations through
      light and holds great potential in all-optical magnetic recording and
      spintronics.

PMID- 29216178
TI  - Chip-scale optical vortex lattice generator on a silicon platform.
AB  - An optical vortex (OV) with an isolated field singularity has been extensively
      studied in a variety of fields. An OV lattice with a network of optical vortices
      may find more advanced applications in widespread areas such as optical
      metrology, optical manipulation, and quantum processing. An OV lattice generated
      by traditional approaches relies on a number of bulky diffractive optical
      elements with large volumes and long working distances. Here we present a simple
      and compact on-chip OV lattice emitter on silicon photonics platforms. The
      principle relies on three-plane-wave interference. We design, fabricate, and
      demonstrate an on-chip OV lattice emitter consisting of three parallel waveguides
      with etched tilt gratings. The tilt gratings facilitate flexible light emission
      in a wide range of directions, enabling the generation of an OV lattice above the
      silicon chip. The demonstrated on-chip OV lattice emitter may open a door to
      generate, manipulate, and detect an OV lattice using photonic integrated
      circuits.

PMID- 29216179
TI  - Magnetron-sputtering deposited WTe2for an ultrafast thulium-doped fiber laser.
AB  - Ultrafast pulse generation was demonstrated in a thulium-doped fiber laser mode
      locked by magnetron-sputtering deposited WTe2 with a modulation depth, a
      nonsaturable loss, and a saturable intensity of 31%, 34.3%, and 7.6  MW/cm2,
      respectively. Stable soliton pulses could be obtained at a 1915.5 nm central
      wavelength with a pulse duration of 1.25 ps, an average output power of 39.9 mW,
      and a signal-to-noise ratio of 95 dB. To the best of our knowledge, this was the
      first demonstration of WTe2-based saturable absorbers in fiber lasers at a 2 MUm
      regime.

PMID- 29216181
TI  - Case report: A rare case of urinary myiasis induced by the fourth instar larvae
      of Telmatoscopus albipunctatus.
AB  - Telmatoscopus albipunctatus, a cosmopolitan fly, is widely distributed throughout
      moist environments. It is one of the most medically important insects (especially
      in urban environments) that may potentially cause myiasis. Urinary myiasis and
      other sites of infestation, including the intestine, nasal passages, lung, and
      derma, have been reported. This is the first case report of a Chinese middlescent
      woman infected with T. albipunctatus in Guangzhou, China. In the present report,
      a 50-year-old woman came to The Third Affiliated Hospital of Southern Medical
      University, Guangzhou, China, because larvae were found when urinating in the
      morning; this had occurred every two days within the past two months. She
      complained of frequent micturition and urgency. Urine tests indicated that all
      indexes were normal except for slight urinary tract infection. Subsequently, the
      larvae were sent to the diagnostic section for parasitic infection in the
      Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University,
      Guangzhou, China. The stereoscopic microscope and transmission electron
      microscope were used for morphological observation. On this basis, the cytochrome
      oxidase subunit 1 (COX1) gene was specifically amplified by PCR. Sequence
      analysis of the PCR product and phylogenetic analysis were used to identify the
      species. Morphological analysis combined with molecular biology methods indicated
      that the insect was the fourth instar larvae of T. albipunctatus. Our results
      show that this was a case of a 50-year-old woman infected with T. albipunctatus
      larvae in her urinary tract, and the findings suggest that clinicians should be
      vigilant for this infection.

PMID- 29216180
TI  - The Ink4a/Arf locus operates as a regulator of the circadian clock modulating RAS
      activity.
AB  - The mammalian circadian clock and the cell cycle are two major biological
      oscillators whose coupling influences cell fate decisions. In the present study,
      we use a model-driven experimental approach to investigate the interplay between
      clock and cell cycle components and the dysregulatory effects of RAS on this
      coupled system. In particular, we focus on the Ink4a/Arf locus as one of the
      bridging clock-cell cycle elements. Upon perturbations by the rat sarcoma viral
      oncogene (RAS), differential effects on the circadian phenotype were observed in
      wild-type and Ink4a/Arf knock-out mouse embryonic fibroblasts (MEFs), which could
      be reproduced by our modelling simulations and correlated with opposing cell
      cycle fate decisions. Interestingly, the observed changes can be attributed to in
      silico phase shifts in the expression of core-clock elements. A genome-wide
      analysis revealed a set of differentially expressed genes that form an intricate
      network with the circadian system with enriched pathways involved in opposing
      cell cycle phenotypes. In addition, a machine learning approach complemented by
      cell cycle analysis classified the observed cell cycle fate decisions as
      dependent on Ink4a/Arf and the oncogene RAS and highlighted a putative fine
      tuning role of Bmal1 as an elicitor of such processes, ultimately resulting in
      increased cell proliferation in the Ink4a/Arf knock-out scenario. This indicates
      that the dysregulation of the core-clock might work as an enhancer of RAS
      mediated regulation of the cell cycle. Our combined in silico and in vitro
      approach highlights the important role of the circadian clock as an Ink4a/Arf
      dependent modulator of oncogene-induced cell fate decisions, reinforcing its
      function as a tumour-suppressor and the close interplay between the clock and the
      cell cycle network.

PMID- 29216182
TI  - The physicochemical fingerprint of Necator americanus.
AB  - Necator americanus, a haematophagous hookworm parasite, infects ~10% of the
      world's population and is considered to be a significant public health risk. Its
      lifecycle has distinct stages, permitting its successful transit from the skin
      via the lungs (L3) to the intestinal tract (L4 maturing to adult). It has been
      hypothesised that the L3 larval sheath, which is shed during percutaneous
      infection (exsheathment), diverts the immune system to allow successful infection
      and reinfection in endemic areas. However, the physicochemical properties of the
      L3 larval cuticle and sheath, which are in direct contact with the skin and its
      immune defences, are unknown. In the present study, we controlled exsheathment,
      to characterise the sheath and underlying cuticle surfaces in situ, using atomic
      force microscopy (AFM) and time-of-flight secondary ion mass spectrometry (ToF
      SIMS). AFM revealed previously unseen surface area enhancing nano-annuli
      exclusive to the sheath surface and confirmed greater adhesion forces exist
      between cationic surfaces and the sheath, when compared to the emergent L3
      cuticle. Furthermore, ToF-SIMS elucidated different chemistries between the
      surfaces of the cuticle and sheath which could be of biological significance. For
      example, the phosphatidylglycerol rich cuticle surface may support the onward
      migration of a lubricated infective stage, while the anionic and potentially
      immunologically active heparan sulphate rich deposited sheath could result in the
      diversion of immune defences to an inanimate antigenic nidus. We propose that our
      initial studies into the surface analysis of this hookworm provides a timely
      insight into the physicochemical properties of a globally important human
      pathogen at its infective stage and anticipate that the development and
      application of this analytical methodology will support translation of these
      findings into a biological context.

PMID- 29216184
TI  - Automated classification of dolphin echolocation click types from the Gulf of
      Mexico.
AB  - Delphinids produce large numbers of short duration, broadband echolocation clicks
      which may be useful for species classification in passive acoustic monitoring
      efforts. A challenge in echolocation click classification is to overcome the many
      sources of variability to recognize underlying patterns across many detections.
      An automated unsupervised network-based classification method was developed to
      simulate the approach a human analyst uses when categorizing click types:
      Clusters of similar clicks were identified by incorporating multiple click
      characteristics (spectral shape and inter-click interval distributions) to
      distinguish within-type from between-type variation, and identify distinct,
      persistent click types. Once click types were established, an algorithm for
      classifying novel detections using existing clusters was tested. The automated
      classification method was applied to a dataset of 52 million clicks detected
      across five monitoring sites over two years in the Gulf of Mexico (GOM). Seven
      distinct click types were identified, one of which is known to be associated with
      an acoustically identifiable delphinid (Risso's dolphin) and six of which are not
      yet identified. All types occurred at multiple monitoring locations, but the
      relative occurrence of types varied, particularly between continental shelf and
      slope locations. Automatically-identified click types from autonomous seafloor
      recorders without verifiable species identification were compared with clicks
      detected on sea-surface towed hydrophone arrays in the presence of visually
      identified delphinid species. These comparisons suggest potential species
      identities for the animals producing some echolocation click types. The network
      based classification method presented here is effective for rapid, unsupervised
      delphinid click classification across large datasets in which the click types may
      not be known a priori.

PMID- 29216183
TI  - Presentation of life-threatening invasive nontyphoidal Salmonella disease in
      Malawian children: A prospective observational study.
AB  - Nontyphoidal Salmonellae commonly cause invasive disease in African children that
      is often fatal. The clinical diagnosis of these infections is hampered by the
      absence of a clear clinical syndrome. Drug resistance means that empirical
      antibiotic therapy is often ineffective and currently no vaccine is available.
      The study objective was to identify risk factors for mortality among children
      presenting to hospital with invasive Salmonella disease in Africa. We conducted a
      prospective study enrolling consecutive children with microbiologically-confirmed
      invasive Salmonella disease admitted to Queen Elizabeth Central Hospital,
      Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were
      used to identify children at risk of inpatient mortality through logistic
      regression modeling. Over one calendar year, 263 consecutive children presented
      with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and
      52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263
      (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263
      children presented with bacteremia, 6 with meningitis and 6 with both.
      Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%;
      95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had
      an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8
      35.1), dyspnea (OR 4.2; 95%CI 1.5-12.0) and HIV infection (OR 3.3; 95%CI 1.1
      10.2) were independent risk factors for inpatient mortality. Invasive Salmonella
      disease in Malawi is characterized by high mortality and prevalence of multi-drug
      resistant isolates, along with non-specific presentation. Young infants, children
      with dyspnea and HIV-infected children bear a disproportionate burden of the
      Salmonella-associated mortality in Malawi. Strategies to improve prevention,
      diagnosis and management of invasive Salmonella disease should be targeted at
      these children.

PMID- 29216185
TI  - A cyber-linked undergraduate research experience in computational biomolecular
      structure prediction and design.
AB  - Computational biology is an interdisciplinary field, and many computational
      biology research projects involve distributed teams of scientists. To accomplish
      their work, these teams must overcome both disciplinary and geographic barriers.
      Introducing new training paradigms is one way to facilitate research progress in
      computational biology. Here, we describe a new undergraduate program in
      biomolecular structure prediction and design in which students conduct research
      at labs located at geographically-distributed institutions while remaining
      connected through an online community. This 10-week summer program begins with
      one week of training on computational biology methods development, transitions to
      eight weeks of research, and culminates in one week at the Rosetta annual
      conference. To date, two cohorts of students have participated, tackling research
      topics including vaccine design, enzyme design, protein-based materials,
      glycoprotein modeling, crowd-sourced science, RNA processing, hydrogen bond
      networks, and amyloid formation. Students in the program report outcomes
      comparable to students who participate in similar in-person programs. These
      outcomes include the development of a sense of community and increases in their
      scientific self-efficacy, scientific identity, and science values, all predictors
      of continuing in a science research career. Furthermore, the program attracted
      students from diverse backgrounds, which demonstrates the potential of this
      approach to broaden the participation of young scientists from backgrounds
      traditionally underrepresented in computational biology.

PMID- 29216186
TI  - Ten simple rules for international short-term research stays.

PMID- 29216187
TI  - A thermostable messenger RNA based vaccine against rabies.
AB  - Although effective rabies virus vaccines have been existing for decades, each
      year, rabies virus infections still cause around 50.000 fatalities worldwide.
      Most of these cases occur in developing countries, where these vaccines are not
      available. The reasons for this are the prohibitive high costs of cell culture or
      egg grown rabies virus vaccines and the lack of a functional cold chain in many
      regions in which rabies virus is endemic. Here, we describe the excellent
      temperature resistance of a non-replicating mRNA based rabies virus vaccine
      encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine
      from -80 degrees C to up to +70 degrees C for several months did not impact the
      protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated
      by the induction of rabies specific virus neutralizing antibodies and protection
      in mice against lethal rabies infection. Moreover, storing the vaccine at
      oscillating temperatures between +4 degrees  and +56 degrees C for 20 cycles in
      order to simulate interruptions of the cold chain during vaccine transport, did
      not affect the vaccine's immunogenicity and protective characteristics,
      indicating that maintenance of a cold chain is not essential for this vaccine.

PMID- 29216188
TI  - Monitoring wound healing in a 3D wound model by hyperspectral imaging and
      efficient clustering.
AB  - Wound healing is a complex and dynamic process with different distinct and
      overlapping phases from homeostasis, inflammation and proliferation to
      remodelling. Monitoring the healing response of injured tissue is of high
      importance for basic research and clinical practice. In traditional application,
      biological markers characterize normal and abnormal wound healing. Understanding
      functional relationships of these biological processes is essential for
      developing new treatment strategies. However, most of the present techniques (in
      vitro or in vivo) include invasive microscopic or analytical tissue sampling. In
      the present study, a non-invasive alternative for monitoring processes during
      wound healing is introduced. Within this context, hyperspectral imaging (HSI) is
      an emerging and innovative non-invasive imaging technique with different
      opportunities in medical applications. HSI acquires the spectral reflectance of
      an object, depending on its biochemical and structural characteristics. An in
      vitro 3-dimensional (3-D) wound model was established and incubated without and
      with acute and chronic wound fluid (AWF, CWF), respectively. Hyperspectral images
      of each individual specimen of this 3-D wound model were assessed at day 0/5/10
      in vitro, and reflectance spectra were evaluated. For analysing the complex
      hyperspectral data, an efficient unsupervised approach for clustering massive
      hyperspectral data was designed, based on efficient hierarchical decomposition of
      spectral information according to archetypal data points. It represents, to the
      best of our knowledge, the first application of an advanced Data Mining approach
      in context of non-invasive analysis of wounds using hyperspectral imagery. By
      this, temporal and spatial pattern of hyperspectral clusters were determined
      within the tissue discs and among the different treatments. Results from non
      invasive imaging were compared to the number of cells in the various clusters,
      assessed by Hematoxylin/Eosin (H/E) staining. It was possible to correlate cell
      quantity and spectral reflectance during wound closure in a 3-D wound model in
      vitro.

PMID- 29216189
TI  - New intraocular pressure measurement method using reflected pneumatic pressure
      from cornea deformed by air puff of ring-type nozzle.
AB  - In this study, a non-contact type intraocular pressure (IOP) measuring system
      using reflected pneumatic pressure is proposed to overcome the disadvantages of
      existing measurement systems. A ring-type nozzle, a key component in the proposed
      system, is designed via computational fluid analysis. It predicts the reflected
      pneumatic pressure based on the nozzle exit angle and inner and outer diameters
      of the nozzle, which are 30 degrees , 7 mm, and 9 mm, respectively. Performance
      evaluation is conducted using artificial eyes fabricated using
      polydimethylsiloxane with the specifications of human eyes. The IOP of the
      fabricated artificial eyes is adjusted to 10, 30, and 50 mm Hg, and the reflected
      pneumatic pressure is measured as a function of the distance between the ring
      type nozzle and artificial eye. The measured reflected pneumatic pressure is high
      when the measurement distance is short and eye pressure is low. The cornea of an
      artificial eye is significantly deformed at a low IOP, and the applied pneumatic
      pressure is more concentrated in front of the ring-type nozzle because of the
      deformed cornea. Thus, the reflected pneumatic pressure at a low IOP has more
      inflows into the pressure sensor inserted inside the nozzle. The sensitivity of
      the output based on the IOP at measurement distances between 3-5 mm is -0.0027, 
      0.0022, -0.0018, -0.0015, and -0.0012. Sensitivity decreases as the measurement
      distance increases. In addition, the reflected pneumatic pressure owing to the
      misalignment at the measurement distances of 3-5 mm is not affected within a
      range of 0.5 mm. Therefore, the measurement range is acceptable up to a 1 mm
      diameter from the center of an artificial eye. However, the accuracy gradually
      decreases as the reflected pneumatic pressure from a misalignment of 1 mm or more
      decreases by 26% or more.

PMID- 29216190
TI  - Quality of reporting in oncology phase II trials: A 5-year assessment through
      systematic review.
AB  - BACKGROUND: Phase II clinical trials are a cornerstone of the development in
      experimental treatments They work as a "filter" for phase III trials
      confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is
      significantly higher than in any other medical specialty. This suggests phase II
      trials in oncology fail to achieve their goal. Objective The present study aims
      at estimating the quality of reporting in published oncology phase II clinical
      trials. DATA SOURCES: A literature review was conducted among all phase II and
      phase II/III clinical trials published during a 5-year period (2010-2015). STUDY
      ELIGIBILITY CRITERIA: All articles electronically published by three randomly
      selected oncology journals with Impact-Factors>4 were included: Journal of
      Clinical Oncology, Annals of Oncology and British Journal of Cancer.
      INTERVENTION: Quality of reporting was assessed using the Key Methodological
      Score. RESULTS: 557 articles were included. 315 trials were single-arm studies
      (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple
      arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3
      (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146
      (26.2%) articles. The primary end point is almost systematically reported
      (90.5%), while sample size calculation is missing in 66% of the articles. 3
      variables were independently associated with reporting of a high standard:
      presence of statistical design (p-value <0.001), multicenter trial (p-value =
      0.012), per-protocol analysis (p-value <0.001). LIMITATIONS: Screening was mainly
      performed by a sole author. The Key Methodological Score was based on only 3
      items, making grey zones difficult to translate. CONCLUSIONS & IMPLICATIONS OF
      KEY FINDINGS: This literature review highlights the existence of gaps concerning
      the quality of reporting. It therefore raised the question of the suitability of
      the methodology as well as the quality of these trials, reporting being
      incomplete in the corresponding articles.

PMID- 29216191
TI  - Transcription factors, coregulators, and epigenetic marks are linearly correlated
      and highly redundant.
AB  - The DNA microstates that regulate transcription include sequence-specific
      transcription factors (TFs), coregulatory complexes, nucleosomes, histone
      modifications, DNA methylation, and parts of the three-dimensional architecture
      of genomes, which could create an enormous combinatorial complexity across the
      genome. However, many proteins and epigenetic marks are known to colocalize,
      suggesting that the information content encoded in these marks can be compressed.
      It has so far proved difficult to understand this compression in a systematic and
      quantitative manner. Here, we show that simple linear models can reliably predict
      the data generated by the ENCODE and Roadmap Epigenomics consortia. Further, we
      demonstrate that a small number of marks can predict all other marks with high
      average correlation across the genome, systematically revealing the substantial
      information compression that is present in different cell lines. We find that the
      linear models for activating marks are typically cell line-independent, while
      those for silencing marks are predominantly cell line-specific. Of particular
      note, a nuclear receptor corepressor, transducin beta-like 1 X-linked receptor 1
      (TBLR1), was highly predictive of other marks in two hematopoietic cell lines.
      The methodology presented here shows how the potentially vast complexity of TFs,
      coregulators, and epigenetic marks at eukaryotic genes is highly redundant and
      that the information present can be compressed onto a much smaller subset of
      marks. These findings could be used to efficiently characterize cell lines and
      tissues based on a small number of diagnostic marks and suggest how the DNA
      microstates, which regulate the expression of individual genes, can be specified.

PMID- 29216192
TI  - Tracking the career development of scientists in low- and middle-income countries
      trained through TDR's research capacity strengthening programmes: Learning from
      monitoring and impact evaluation.
AB  - The Special Programme for Research and Training in Tropical Diseases (TDR) co
      sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research
      capacity strengthening in low- and middle-income countries for over 40 years. In
      order to assess and continuously optimize its capacity strengthening approaches,
      an evaluation of the influence of TDR training grants on research career
      development was undertaken. The assessment was part of a larger evaluation
      conducted by the European Science Foundation. A comprehensive survey
      questionnaire was developed and sent to a group of 117 trainees supported by TDR
      who had completed their degree (masters or PhD) between 2000 and 2012; of these,
      seventy seven (77) responded. Most of the respondents (80%) rated TDR support as
      a very important factor that influenced their professional career achievements.
      The "brain drain" phenomenon towards high-income countries was particularly low
      amongst TDR grantees: the rate of return to their region of origin upon
      completion of their degree was 96%. A vast majority of respondents are still
      working in research (89%), with 81% of respondents having participated in
      multidisciplinary research activities; women engaged in multidisciplinary
      collaboration to a higher extent than men. However, only a minority of all have
      engaged in intersectoral collaboration, an aspect that would require further
      study. The post-degree career choices made by the respondents were strongly
      influenced by academic considerations. At the time of the survey, 92% of all
      respondents hold full-time positions, mainly in the public sector. Almost 25% of
      the respondents reported that they had influenced policy and practice changes.
      Some of the challenges and opportunities faced by trainees at various stages of
      their research career have been identified. Modalities to overcome these will
      require further investigation. The survey evidenced how TDR's research capacity
      grant programmes made a difference on researchers' career development and on
      south-south collaborations, by strengthening and localizing research capacity in
      lower income regions, and also showed there is more that needs to be done. The
      factors involved, challenges and lessons learnt may help donors and policy makers
      improve their future interventions with regard to designing capacity
      strengthening programmes and setting funding priorities.

PMID- 29216193
TI  - Community prevalence of chronic respiratory symptoms in rural Malawi:
      Implications for policy.
AB  - BACKGROUND: No community prevalence studies have been done on chronic respiratory
      symptoms of cough, wheezing and shortness of breath in adult rural populations in
      Malawi. Case detection rates of tuberculosis (TB) and chronic airways disease are
      low in resource-poor primary health care facilities. OBJECTIVE: To understand the
      prevalence of chronic respiratory symptoms and recorded diagnoses of TB in rural
      Malawian adults in order to improve case detection and management of these
      diseases. METHODS: A population proportional, cross-sectional study was conducted
      to determine the proportion of the population with chronic respiratory symptoms
      that had a diagnosis of tuberculosis or chronic airways disease in two rural
      communities in Malawi. Households were randomly selected using Google Earth Pro
      software. Smart phones loaded with Open Data Kit Essential software were used for
      data collection. Interviews were conducted with 15795 people aged 15 years and
      above to enquire about symptoms of chronic cough, wheeze and shortness of breath.
      RESULTS: Overall 3554 (22.5%) participants reported at least one of these
      respiratory symptoms. Cough was reported by 2933, of whom 1623 (55.3%) reported
      cough only and 1310 (44.7%) combined with wheeze and/or shortness of breath. Only
      4.6% (164/3554) of participants with chronic respiratory symptoms had one or more
      of the following diagnoses in their health passports (patient held medical
      records): TB, asthma, bronchitis and chronic obstructive pulmonary disease).
      CONCLUSIONS: The high prevalence of chronic respiratory symptoms coupled with
      limited recorded diagnoses in patient-held medical records in these rural
      communities suggests a high chronic respiratory disease burden and unmet health
      need.

PMID- 29216194
TI  - Partitioning no-take marine reserve (NTMR) and benthic habitat effects on density
      of small and large-bodied tropical wrasses.
AB  - No-take marine reserves (NTMRs) are increasingly implemented for fisheries
      management and biodiversity conservation. Yet, assessing NTMR effectiveness
      depends on partitioning the effects of NTMR protection and benthic habitat on
      protected species. Such partitioning is often difficult, since most studies lack
      well-designed sampling programs (i.e. Before-After-Control-Impact-Pair designs)
      spanning long-term time scales. Spanning 31 years, this study quantifies the
      effects of NTMR protection and changes to benthic habitat on the density of
      tropical wrasses (F. Labridae) at Sumilon and Apo Islands, Philippines. Five
      species of wrasse were studied: two species of large-bodied (40-50 cm TL)
      Hemigymnus that were vulnerable to fishing, and three species of small-bodied (10
      25 cm TL) Thalassoma and Cirrhilabrus that were not targeted by fishing. NTMR
      protection had no measurable effect on wrasse density, irrespective of species or
      body size, over 20 (Sumilon) and 31 (Apo) years of protection. However, the
      density of wrasses was often affected strongly by benthic cover. Hemigymnus spp.
      had a positive association with hard coral cover, while Thalassoma spp. and
      Cirrhilabrus spp. had strong positive associations with cover of rubble and dead
      substratum. These associations were most apparent after environmental
      disturbances (typhoons, coral bleaching, crown of thorns starfish (COTS)
      outbreaks, use of explosives and drive nets) reduced live hard coral cover and
      increased cover of rubble, dead substratum and sand. Disturbances that reduced
      hard coral cover often reduced the density of Hemigymnus spp. and increased the
      density of Thalassoma spp. and Cirrhilabrus spp. rapidly (1-2 years). As hard
      coral recovered, density of Hemigymnus spp. often increased while density of
      Thalassoma spp. and Cirrhilabrus spp. often decreased, often on scales of 5-10
      years. This study demonstrates that wrasse population density was influenced more
      by changes to benthic cover than by protection from fishing.

PMID- 29216195
TI  - Reduced visual attention in heterogeneous textures is reflected in occipital
      alpha and theta band activity.
AB  - Increasing context heterogeneity has been found to reduce attention deployment
      towards an embedded target item. Heterogeneity in visual search tasks is
      typically induced by segmenting the background into several perceptual groups. In
      the present study, however, context heterogeneity was induced by varying whole
      field heterogeneity, i.e., the degree of distractor variability within the entire
      context. This allowed us to (i) more gradually vary context heterogeneity, and
      (ii) investigate attention deployment on a whole-field scale. Results showed that
      both search performance and amplitude of the N2pc (lateralized ERP; posterior
      contralateral negativity in the N2 range) monotonically decreased with increasing
      context heterogeneity, which confirmed that there was less efficient attention
      deployment for more heterogeneous contexts. The amplitude of the bilateral N2
      exhibited a U-shaped function, suggesting global perception for the lowest and
      highest levels of heterogeneity, but local processing for intermediate
      heterogeneity levels. Independent component analyses revealed an occipital ERP
      contributing effective source cluster that may reflect stimulus representations
      on a saliency map. With increasing heterogeneity, these sources exhibited more
      theta band activity for distractors and less theta band activity for targets.
      Alpha band activity of a second component cluster varied with heterogeneity
      level, and low-theta/delta activity of a third source cluster distinguished
      target presence versus absence. In sum, our results suggest that independent
      brain sources contributed to the differential processing of heterogeneous versus
      homogeneous contexts.

PMID- 29216196
TI  - Loss of epithelial markers is an early event in oral dysplasia and is observed
      within the safety margin of dysplastic and T1 OSCC biopsies.
AB  - Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is
      associated with poor 5-year patient survival. Disease treatment is further
      compounded by the difficulty in predicting pre-cancerous tissues that will
      progress to OSCC and the high recurrence rates following surgical resection. Here
      we have assessed expression of the oral epithelial markers E-cadherin, EMP1 and
      5T4 and the pro-invasive N-cadherin proteins using fully characterised antibodies
      and quantitative immunofluorescence microscopy in normal tissue (NT),
      fibroepithelial polyp (FEP), low-grade dysplasia (LGD), high-grade dysplasia
      (HGD), T1 OSCC and T4 OSCC biopsies. Decreased E-cadherin expression was
      associated with FEP, LGD and HGD biopsies, demonstrating that loss of E-cadherin
      is an early event within abnormal epithelium and occurs in the absence of an E-
      to N-cadherin switch, the latter of which was only observed in T4 OSCC.
      Furthermore, loss of E-cadherin and EMP1 is an indicator of LGD (p = 0.0006) and
      loss of E-cadherin, EMP1 and 5T4 an indicator of HGD (p = 0.0006). Expression
      patterns of E-cadherin, EMP1 and N-cadherin could predict abnormal epithelium in
      LGD, HGD, T1 and T4 OSCC biopsies (z-value = 0 for all disease grades) and
      allowed classification of LGD (z = 1.47), HGD (z = 2.138), T1 (z = 1.05) and T4
      OSCC (z = 1.49) biopsies. Therefore, these markers provide a useful means to
      predict abnormal epithelium in patient biopsies. Linear regression and
      coefficient of determination analysis revealed positive correlation with a
      NT>LGD>HGD disease transition but low correlation with a putative HGD>T1 OSCC>T4
      OSCC disease transition. Furthermore, expression of E-cadherin, EMP1, 5T4 and N
      cadherin in pathologically normal surgical safety margins of LGD, HGD and T1 OSCC
      patient biopsies revealed significant differences to NT and the use of safety
      margins or FEP as 'normal tissue' controls introduced Type II errors in all
      patient cohorts. This work forms the basis for further investigation of the role
      of E-cadherin loss in abnormal epithelium and in the development of automated
      analyses for use in cancer diagnostics.

PMID- 29216197
TI  - Shift toward greater pathologic post-myocardial infarction remodeling with loss
      of the adaptive hypertrophic signaling of alpha1 adrenergic receptors in mice.
AB  - RATIONALE: We have hypothesized that post-infarction cardiac remodeling can be
      influenced by shifts in the balance between intracellular mediators of
      "pathologic" and "physiologic" hypertrophy. Although alpha1 adrenergic receptors
      (alpha1-ARs) mediate pro-adaptive hypertrophy during pressure overload, little is
      known about their role or downstream mediators after myocardial infarction.
      METHODS: We performed loss-of-function experiments via coronary ligation in
      alpha1A-AR knockout (AKO) mice. Post-myocardial infarction (MI) remodeling was
      evaluated via echocardiography, quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of cardiac fetal gene expression, histologic
      analysis of myocyte size, post-MI fibrosis and apoptosis, and Western blot
      analysis of apoptotic regulators. RESULTS: Alpha1A-AR knockout paradoxically
      increased post-MI hypertrophy compared to wild type controls (WT), but also
      increased ventricular dilatation, fibrosis, apoptosis, and 4-week post-MI
      mortality (64% in AKO vs. 25% in WT, P = 0.02), suggesting a shift toward greater
      pathologic hypertrophy in the absence of pro-adaptive alpha1A effects. alpha1A-AR
      knockout increased phospho-p38 levels in the pre-MI myocardium compared to WT
      (0.55 +/- 0.16 vs. 0.03 +/- 0.01, P<0.05) but decreased phospho-ERK1/2 post-MI
      (0.49 +/- 0.35 arbitrary units vs. 1.55 +/- 0.43 in WT, P<0.05). Furthermore,
      expression of pro-apoptotic factor Bax was increased (1.19 +/- 0.15 vs. 0.78 +/-
      0.08, P<0.05) and expression of anti-apoptotic factors Bcl2 was decreased (0.26
      +/- 0.01 vs. 0.55 +/- 0.06, P<0.01) compared to WT. CONCLUSIONS: Alpha1A-AR
      provides an important counterbalance to pathologic pathways during post-MI
      remodeling that may be mediated through ERK1/2 signaling; these observations
      provide support for further development of an alpha1A-AR/ERK-based molecular
      intervention for this chronic, often fatal disease.

PMID- 29216198
TI  - HCV kinetic and modeling analyses project shorter durations to cure under
      combined therapy with daclatasvir and asunaprevir in chronic HCV-infected
      patients.
AB  - BACKGROUND & AIMS: High cure rates are achieved in HCV genotype-1b patients
      treated with daclatasvir and asunaprevir, DCV/ASV. Here we analyzed early HCV
      kinetics in genotype-1b infected Japanese subjects treated with DCV/ASV and
      retrospectively projected, using mathematical modeling, whether shorter treatment
      durations might be effective. METHODS: HCV RNA levels were measured frequently
      during DCV/ASV therapy in 95 consecutively treated patients at a single center in
      Japan. Mathematical modeling was used to predict the time to cure, i.e, <1 virus
      copy in the extracellular body fluid. Patients with HCV<15 IU/ml at week 1 (n =
      27) were excluded from modeling analysis due to insufficient HCV RNA data points.
      RESULTS: Eighty nine of the 95 included patients (94%) achieved cure, 3 (3%)
      relapsed due to treatment-emergent resistance, and 3 (3%) completed therapy but
      were lost during follow up. Model fits from 68 patients with sufficient data
      points indicate that after a short pharmacological delay (15.4 min [relative
      standard error, rse = 26%]), DCV/ASV effectiveness in blocking HCV production was
      0.999 [rse~0%], HCV half-life in blood was t1/2 = 1.7 hr [rse = 21%], and HCV
      infected cell loss rate was 0.391/d [rse = 5%]. Modeling predicted that 100% and
      98.5% of patients who had HCV<15 IU/ml at days 14 and 28 might have been cured
      with 6 and 8 weeks of therapy, respectively. There was a trend (p = 0.058)
      between younger age and shorter time to cure. CONCLUSION: Modeling early HCV
      kinetics under DCV/ASV predicts that most patients would achieve cure with short
      treatment durations, suggesting that 24 weeks of DCV/ASV treatment can be
      significantly shortened.

PMID- 29216200
TI  - Development and application of coupled system dynamics and game theory: A dynamic
      water conflict resolution method.
AB  - Conflicts over water resources can be highly dynamic and complex due to the
      various factors which can affect such systems, including economic, engineering,
      social, hydrologic, environmental and even political, as well as the inherent
      uncertainty involved in many of these factors. Furthermore, the conflicting
      behavior, preferences and goals of stakeholders can often make such conflicts
      even more challenging. While many game models, both cooperative and non
      cooperative, have been suggested to deal with problems over utilizing and sharing
      water resources, most of these are based on a static viewpoint of demand points
      during optimization procedures. Moreover, such models are usually developed for a
      single reservoir system, and so are not really suitable for application to an
      integrated decision support system involving more than one reservoir. This paper
      outlines a coupled simulation-optimization modeling method based on a combination
      of system dynamics (SD) and game theory (GT). The method harnesses SD to capture
      the dynamic behavior of the water system, utilizing feedback loops between the
      system components in the course of the simulation. In addition, it uses GT
      concepts, including pure-strategy and mixed-strategy games as well as the Nash
      Bargaining Solution (NBS) method, to find the optimum allocation decisions over
      available water in the system. To test the capability of the proposed method to
      resolve multi-reservoir and multi-objective conflicts, two different
      deterministic simulation-optimization models with increasing levels of complexity
      were developed for the Langat River basin in Malaysia. The later is a strategic
      water catchment that has a range of different stakeholders and managerial bodies,
      which are however willing to cooperate in order to avoid unmet demand. In our
      first model, all water users play a dynamic pure-strategy game. The second model
      then adds in dynamic behaviors to reservoirs to factor in inflow uncertainty and
      adjust the strategies for the reservoirs using the mixed-strategy game and Markov
      chain methods. The two models were then evaluated against three performance
      indices: Reliability, Resilience and Vulnerability (R-R-V). The results showed
      that, while both models were well capable of dealing with conflict resolution
      over water resources in the Langat River basin, the second model achieved a
      substantially improved performance through its ability to deal with dynamicity,
      complexity and uncertainty in the river system.

PMID- 29216199
TI  - The potential of statistical shape modelling for geometric morphometric analysis
      of human teeth in archaeological research.
AB  - This paper introduces statistical shape modelling (SSM) for use in
      osteoarchaeology research. SSM is a full field, multi-material analytical
      technique, and is presented as a supplementary geometric morphometric (GM) tool.
      Lower mandibular canines from two archaeological populations and one modern
      population were sampled, digitised using micro-CT, aligned, registered to a
      baseline and statistically modelled using principal component analysis (PCA).
      Sample material properties were incorporated as a binary enamel/dentin parameter.
      Results were assessed qualitatively and quantitatively using anatomical
      landmarks. Finally, the technique's application was demonstrated for inter-sample
      comparison through analysis of the principal component (PC) weights. It was found
      that SSM could provide high detail qualitative and quantitative insight with
      respect to archaeological inter- and intra-sample variability. This technique has
      value for archaeological, biomechanical and forensic applications including
      identification, finite element analysis (FEA) and reconstruction from partial
      datasets.

PMID- 29216201
TI  - Functional lung MRI for regional monitoring of patients with cystic fibrosis.
AB  - PURPOSE: To test quantitative functional lung MRI techniques in young adults with
      cystic fibrosis (CF) compared to healthy volunteers and to monitor immediate
      treatment effects of a single inhalation of hypertonic saline in comparison to
      clinical routine pulmonary function tests. MATERIALS AND METHODS: Sixteen
      clinically stable CF patients and 12 healthy volunteers prospectively underwent
      two functional lung MRI scans and pulmonary function tests before and 2h after a
      single treatment of inhaled hypertonic saline or without any treatment. MRI
      derived oxygen enhanced T1 relaxation measurements, fractional ventilation, first
      pass perfusion parameters and a morpho-functional CF-MRI score were acquired.
      RESULTS: Compared to healthy controls functional lung MRI detected and quantified
      significantly increased ventilation heterogeneity in CF patients. Regional
      functional lung MRI measures of ventilation and perfusion as well as the CF-MRI
      score and pulmonary function tests could not detect a significant treatment
      effect two hours after a single treatment with hypertonic saline in young adults
      with CF (p>0.05). CONCLUSION: This study shows the feasibility of functional lung
      MRI as a non-invasive, radiation-free tool for monitoring patients with CF.

PMID- 29216202
TI  - Composition and variation of respiratory microbiota in healthy military
      personnel.
AB  - Certain occupational and geographical exposures have been associated with an
      increased risk of lung disease. As a baseline for future studies, we sought to
      characterize the upper respiratory microbiomes of healthy military personnel in a
      garrison environment. Nasal, oropharyngeal, and nasopharyngeal swabs were
      collected from 50 healthy active duty volunteers eight times over the course of
      one year (1107 swabs, completion rate = 92.25%) and subjected to pyrosequencing
      of the V1-V3 region of 16S rDNA. Respiratory bacterial taxa were characterized at
      the genus level, using QIIME 1.8 and the Ribosomal Database Project classifier.
      High levels of Staphylococcus, Corynebacterium, and Propionibacterium were
      observed among both nasal and nasopharyngeal microbiota, comprising more than 75%
      of all operational taxonomical units (OTUs). In contrast, Streptococcus was the
      sole dominant bacterial genus (approximately 50% of all OTUs) in the oropharynx.
      The average bacterial diversity was greater in the oropharynx than in the nasal
      or nasopharyngeal region at all time points. Diversity analysis indicated a
      significant overlap between nasal and nasopharyngeal samples, whereas
      oropharyngeal samples formed a cluster distinct from these two regions. The study
      produced a large set of pyrosequencing data on the V1-V3 region of bacterial 16S
      rDNA for the respiratory microbiomes of healthy active duty Service Members. Pre
      processing of sequencing reads showed good data quality. The derived microbiome
      profiles were consistent both internally and with previous reports, suggesting
      their utility for further analyses and association studies based on sequence and
      demographic data.

PMID- 29216204
TI  - Aerodynamics of a highly irregular body at transonic speeds-Analysis of STRATOS
      flight data.
AB  - In this paper, we analyze the trajectory and body attitude data of Felix
      Baumgartner's supersonic free fall through the atmosphere on October 14, 2012. As
      one of us (UW) was scientific advisor to the Red Bull Stratos team, the analysis
      is based on true body data (body mass, wetted pressure suit surface area) and
      actual atmospheric data from weather balloon measurements. We also present a
      fully developed theoretical analysis and solution of atmospheric free fall. By
      matching the flight data against this solution, we are able to derive and track
      the drag coefficient CD from the subsonic to the transonic and supersonic regime,
      and back again. Although the subsonic drag coefficient is the expected CD = 0.60
      +/- 0.05, surprisingly the transonic compressibility drag coefficient is only 19%
      of the expected value. We provide a plausible explanation for this unexpected
      result.

PMID- 29216203
TI  - Dose responses of vitamin D3 supplementation on arterial stiffness in overweight
      African Americans with vitamin D deficiency: A placebo controlled randomized
      trial.
AB  - BACKGROUND: Clinical trials are scant and equivocal on whether vitamin D can
      ameliorate arterial stiffness, particularly in populations at high risk for
      vitamin D deficiency and cardiovascular disease (CVD). This study determined the
      dose-response effects of vitamin D3 supplementation on arterial stiffness in
      overweight African Americans with vitamin D deficiency. METHODS: Seventy
      overweight African Americans (aged 13-45 years) with serum 25-hydroxyvitamin D
      [25(OH)D] levels <= 20 ng/mL were randomized to monthly oral supplementation of
      18,000 IU (~600 IU/day, n = 17), 60,000 IU (~2000 IU/day, n = 18), or 120,000 IU
      (~4000 IU/day, n = 18) of vitamin D3 or placebo (n = 17) for 16-weeks. The
      arterial stiffness measurements, carotid-femoral pulse wave velocity (PWV) and
      carotid-radial PWV, were assessed by applanation tonometry at baseline and 16
      weeks. RESULTS: Vitamin D3 supplementation demonstrated a dose-response increase
      in serum 25(OH)D concentrations between groups (P<0.01). A significant downward
      linear trend was observed for carotid-femoral PWV (P<0.01), as the mean changes
      in carotid-femoral PWV across the four treatment groups were 0.13 m/s (95% CI: 
      0.24, 0.51 m/s) for placebo, 0.02 m/s (95% CI: -0.34, 0.38 m/s) for 600 IU/day
      group, -0.11 m/s (95% CI: -0.50, 0.27 m/s) for the 2,000 IU/day group, and -0.70
      m/s (95% CI: -1.07, -0.32 m/s) for the 4,000 IU/day group. Findings were similar
      for carotid-radial PWV (P = 0.03), as the mean changes in carotid-radial PWV
      across the four treatment groups were 0.24 m/s (95% CI: -0.45, 0.92 m/s) for
      placebo, 0.09 m/s (95% CI: -0.54, 0.73 m/s) for 600 IU/day group, -0.57 m/s (95%
      CI: -1.20, 0.07 m/s) for the 2,000 IU/day group, and -0.61 m/s (95% CI: -1.25,
      0.02 m/s) for the 4,000 IU/day group. CONCLUSION: Arterial stiffness was improved
      by vitamin D3 supplementation in a dose-response manner in overweight African
      Americans with vitamin D deficiency.

PMID- 29216205
TI  - The impact of viewing a video with and without head phones on snack intake: A
      pilot study.
AB  - Research shows that many small changes to the environment impact one's eating
      behavior. The aim of this study was to examine whether the type of audio
      transmission would affect snack intake depending on the degree of immersion. A
      sample of 174 university students were randomized to either viewing a movie
      wearing headphones or listening over loud speakers while consuming a snack of
      their choice. Significant differences were found with more snacks consumed in the
      group without headphones compared to the group wearing headphones. Particularly
      women tend to eat less (about 10% of the offered snack less) when wearing
      headphones while viewing a movie. The results seem to indicate that audio
      transmission mode might impact eating behavior.

PMID- 29216206
TI  - The psychometric properties of a shortened Dutch version of the consequences
      scale used in the Core Alcohol and Drug Survey.
AB  - BACKGROUND: Alcohol and drug misuse among college students has been studied
      extensively and has been clearly identified as a public health problem. Within
      more general populations alcohol misuse remains one of the leading causes of
      disease, disability and death worldwide. Conducting research on alcohol misuse
      requires valid and reliable instruments to measure its consequences. One scale
      that is often used is the consequences scale in the Core Alcohol and Drug Survey
      (CADS). However, psychometric studies on the CADS are rare and the ones that do
      exist report varying results. This article aims to address this imbalance by
      examining the psychometric properties of a Dutch version of the CADS in a large
      sample of Flemish university and college students. METHODS: The analyses are
      based on data collected by the inter-university project 'Head in the clouds',
      measuring alcohol use among students. In total, 19,253 students participated
      (22.1% response rate). The CADS scale was measured using 19 consequences, and
      participants were asked how often they had experienced these on a 6-point scale.
      Firstly, the factor structure of the CADS was examined. Two models from
      literature were compared by performing confirmatory factor analyses (CFA) and
      were adapted if necessary. Secondly, we assessed the composite reliability as
      well as the convergent, discriminant and concurrent validity. RESULTS: The two
      factor model, identifying personal consequences (had a hangover; got nauseated or
      vomited; missed a class) and social consequences (got into an argument or fight;
      been criticized by someone I know; done something I later regretted; been hurt or
      injured) was indicated to be the best model, having both a good model fit and an
      acceptable composite reliability. In addition, construct validity was evaluated
      to be acceptable, with good discriminant validity, although the convergent
      validity of the factor measuring 'social consequences' could be improved.
      Concurrent validity was evaluated as good. CONCLUSIONS: In deciding which model
      best represents the data, it is crucial that not only the model fit is evaluated,
      but the importance of factor reliability and validity issues is also taken into
      account. The two-factor model, identifying personal consequences and social
      consequences, was concluded to be the best model. This shortened Dutch version of
      the CADS (CADS_D) is a useful tool to screen alcohol-related consequences among
      college students.

PMID- 29216207
TI  - Poisson pre-processing of nonstationary photonic signals: Signals with equality
      between mean and variance.
AB  - Photonic signals are broadly exploited in communication and sensing and they
      typically exhibit Poisson-like statistics. In a common scenario where the
      intensity of the photonic signals is low and one needs to remove a nonstationary
      trend of the signals for any further analysis, one faces an obstacle: due to the
      dependence between the mean and variance typical for a Poisson-like process,
      information about the trend remains in the variance even after the trend has been
      subtracted, possibly yielding artifactual results in further analyses. Commonly
      available detrending or normalizing methods cannot cope with this issue. To
      alleviate this issue we developed a suitable pre-processing method for the
      signals that originate from a Poisson-like process. In this paper, a Poisson pre
      processing method for nonstationary time series with Poisson distribution is
      developed and tested on computer-generated model data and experimental data of
      chemiluminescence from human neutrophils and mung seeds. The presented method
      transforms a nonstationary Poisson signal into a stationary signal with a Poisson
      distribution while preserving the type of photocount distribution and phase-space
      structure of the signal. The importance of the suggested pre-processing method is
      shown in Fano factor and Hurst exponent analysis of both computer-generated model
      signals and experimental photonic signals. It is demonstrated that our pre
      processing method is superior to standard detrending-based methods whenever
      further signal analysis is sensitive to variance of the signal.

PMID- 29216208
TI  - Antiretroviral therapy as a risk factor for chronic kidney disease: Results from
      traditional regression modeling and causal approach in a large observational
      study.
AB  - OBJECTIVE: We investigated whether patients receiving selected antiretroviral
      combinations had a higher risk of chronic kidney disease (CKD) using traditional
      regression modeling and a causal approach in a large prospective cohort. PATIENTS
      AND METHODS: For the purpose of this study, we selected 6301 patients who (i)
      started their first antiretroviral regimen after 1st January 2004, (ii) had at
      least one serum creatinine measurement within 6 months before ART initiation
      (study entry), and (iii) had at least two measurements after study entry.
      Baseline eGFR was defined from the last serum creatinine measurement before study
      entry. All eGFR values were calculated using the Modification of Diet and Renal
      Disease (MDRD) equation. Both traditional Cox proportional hazards model and Cox
      marginal structural models were applied. Distinct coding for antiretroviral
      therapy exposure were investigated as well as double robust estimators. RESULTS:
      Overall we showed that patients receiving tenofovir (TDF) with a ritonavir
      boosted protease inhibitor (rbPI) exhibited a higher risk of CKD compared with
      patients who received TDF with a non-nucleosidic reverse transcriptase inhibitor
      (NNRTI). Such an increased risk was observed considering both initial and current
      regimens. Our analysis revealed a clinician-driven switch away from TDF among
      persons experiencing a decline in renal function while receiving this drug.
      CONCLUSION: Our results show that combination of TDF and boosted protease
      inhibitor is associated with a higher CKD risk than TDF and a NNRTI.

PMID- 29216209
TI  - Preliminary study of tumor heterogeneity in imaging predicts two year survival in
      pancreatic cancer patients.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the
      United States with a five-year survival rate of 7.2% for all stages. Although
      surgical resection is the only curative treatment, currently we are unable to
      differentiate between resectable patients with occult metastatic disease from
      those with potentially curable disease. Identification of patients with poor
      prognosis via early classification would help in initial management including the
      use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative
      adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating
      masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize
      that heterogeneity reflects underlying differences at the histologic or genetic
      level and will therefore correlate with patient outcome. We quantify
      heterogeneity of PDAC with texture analysis to predict 2-year survival. Using
      fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes
      classifier, the proposed features achieve an area under receiver operating
      characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one
      image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross
      validation. We conclude that texture analysis can be used to quantify
      heterogeneity in CT images to accurately predict 2-year survival in patients with
      pancreatic cancer. From these data, we infer differences in the biological
      evolution of pancreatic cancer subtypes measurable in imaging and identify
      opportunities for optimized patient selection for therapy.

PMID- 29216210
TI  - Social relationship changes in victim families due to a social disaster:
      Experiences of student victims' families in the South Korean Sewol ferry
      disaster.
AB  - The Sewol ferry incident on April 16, 2014 in South Korea claimed the lives of
      304 individuals, including about 250 high school students on a school trip. The
      majority of South Korean citizens were watching live updates on the capsized
      Sewol ferry, anxiously watching on TV how the vessel fully sunk over time. They
      were desperately hoping for the rescue of the survivors inside. However, their
      anxiety had become shock, anger, and helplessness, and the disaster has become a
      daunting, collective trauma, not just to the victims and their families, but also
      to the citizens who were exposed only through the media. In this study, we
      interviewed victims' families two years after the incident. We explored how they
      have experienced changes in their social relationships. We conducted semi
      structured interviews of 54 family members of the student victims. We
      qualitatively examined the data applying a thematic analysis. Changes in their
      social relationships were largely divided into the relationships in the proximal
      environment and the relationships in distal environments. The former included
      subcategories such as immediate family, coworkers, friends, relatives, survived
      students and their parents, and concepts corresponding to each subcategory. The
      latter involved subcategories such as neighbors, other citizens, the victims'
      family committee, government, and society, and concepts subject to each
      subcategory. Based on these findings, rehabilitation plans for trauma victims and
      their families should take into account the significant changes in their social
      relationships and the further consequences of those changes.

PMID- 29216211
TI  - Validation of the Japanese version of the Central Sensitization Inventory in
      patients with musculoskeletal disorders.
AB  - BACKGROUND: Many musculoskeletal pain conditions are characterized by
      hypersensitivity, which is induced by central sensitization (CS). A
      questionnaire, the Central Sensitization Inventory (CSI), was recently developed
      to help clinicians identify patients whose presenting symptoms may be related to
      central sensitivity syndrome (CSS). The aims of the present study were to examine
      criterion validity and construct validity of the Japanese version of the CSI (CSI
      J), and to investigate prevalence rates of CS severity levels in patients with
      musculoskeletal disorders. METHODS: Translation of the CSI into Japanese was
      conducted using a forward-backward method. Two hundred and ninety patients with
      musculoskeletal pain disorders completed the resultant CSI-J. A subset of the
      patients (n = 158) completed the CSI-J again one week later. The relationships
      between CSI and clinical symptoms, EuroQol 5-dimension (EQ-5D) and Brief Pain
      Inventory (BPI), were examined for criterion validity. EQ-5D assesses Health
      related QOL and BPI measures pain intensity and pain interference. The
      psychometric properties were evaluated with analyses of construct validity,
      factor structure and internal consistency, and subsequently investigate the
      prevalence rates of CS severity levels. RESULTS: The CSI-J demonstrated high
      internal consistency (Cronbach's alpha = 0.89) and test-retest reliability was
      excellent value (ICC = 0.85). The CSI-J was significantly correlated with EQ-5D
      (r = -0.44), pain intensity (r = 0.42), and pain interference (r = 0.48) (p <
      0.01 for all). Ten percent of the participants were above the cutoff "40". The
      exploratory factor analysis resulted in 5-factor model. CONCLUSIONS: This study
      reported that the CSI-J was a useful and psychometrically sound tool to assess
      CSS in Japanese patients with musculoskeletal disorders. The finding of the
      prevalence rates of CS severity levels in patients with musculoskeletal disorders
      may help clinicians to decide strategy of treatment.

PMID- 29216212
TI  - The gender gap in self-rated health and education in Spain. A multilevel
      analysis.
AB  - BACKGROUND: Women tend to report poorer self-rated health than men. It is also
      well established that education has a positive effect on health. However, the
      issue of how the benefits of education on health differ between men and women has
      not received enough attention and the few existing studies which do focus on the
      subject do not draw a clear conclusion. Therefore, this study aims to analyse
      whether the positive influence of educational attainment on health is higher for
      women and whether education helps to overcome the gender gap in self-rated
      health. METHODS: We analyse cross-sectional data from the 2012 European Union
      statistics on income and living conditions. We use a logit regression model with
      odds ratios and a multilevel perspective to carry out a study which includes
      several individual and contextual control variables. We focused our study on the
      working population in Spain aged between 25 and 65. The final sample considered
      is composed of 14,120 subjects: 7,653 men and 6,467 women. RESULTS: There is a
      gender gap in self-rated health only for the less educated. This gap is not
      statistically significant among more highly educated individuals. Attaining a
      high level of education has the same positive effect on both women's and men's
      self-rated health. CONCLUSIONS: Although we did not find gender disparities when
      considering the effect of education on health, we show that women's health is
      poorer among the less educated, mainly due to labour precariousness and household
      conditions.

PMID- 29216213
TI  - A multi-scale spatial model of hepatitis-B viral dynamics.
AB  - Chronic hepatitis B viral infection (HBV) afflicts around 250 million individuals
      globally and few options for treatment exist. Once infected, the virus entrenches
      itself in the liver with a notoriously resilient colonisation of viral DNA
      (covalently-closed circular DNA, cccDNA). The majority of infections are cleared,
      yet we do not understand why 5% of adult immune responses fail leading to the
      chronic state with its collateral morbid effects such as cirrhosis and eventual
      hepatic carcinoma. The liver environment exhibits particularly complex spatial
      structures for metabolic processing and corresponding distributions of nutrients
      and transporters that may influence successful HBV entrenchment. We assembled a
      multi-scaled mathematical model of the fundamental hepatic processing unit, the
      sinusoid, into a whole-liver representation to investigate the impact of this
      intrinsic spatial heterogeneity on the HBV dynamic. Our results suggest HBV may
      be exploiting spatial aspects of the liver environment. We distributed increased
      HBV replication rates coincident with elevated levels of nutrients in the
      sinusoid entry point (the periportal region) in tandem with similar distributions
      of hepatocyte transporters key to HBV invasion (e.g., the sodium-taurocholate
      cotransporting polypeptide or NTCP), or immune system activity. According to our
      results, such co-alignment of spatial distributions may contribute to persistence
      of HBV infections, depending on spatial distributions and intensity of immune
      response as well. Moreover, inspired by previous HBV models and experimentalist
      suggestions of extra-hepatic HBV replication, we tested in our model influence of
      HBV blood replication and observe an overall nominal effect on persistent liver
      infection. Regardless, we confirm prior results showing a solo cccDNA is
      sufficient to re-infect an entire liver, with corresponding concerns for
      transplantation and treatment.

PMID- 29216214
TI  - Complete synchronization of the global coupled dynamical network induced by
      Poisson noises.
AB  - The different Poisson noise-induced complete synchronization of the global
      coupled dynamical network is investigated. Based on the stability theory of
      stochastic differential equations driven by Poisson process, we can prove that
      Poisson noises can induce synchronization and sufficient conditions are
      established to achieve complete synchronization with probability 1. Furthermore,
      numerical examples are provided to show the agreement between theoretical and
      numerical analysis.

PMID- 29216215
TI  - Accelerating cross-validation with total variation and its application to super
      resolution imaging.
AB  - We develop an approximation formula for the cross-validation error (CVE) of a
      sparse linear regression penalized by l1-norm and total variation terms, which is
      based on a perturbative expansion utilizing the largeness of both the data
      dimensionality and the model. The developed formula allows us to reduce the
      necessary computational cost of the CVE evaluation significantly. The
      practicality of the formula is tested through application to simulated black-hole
      image reconstruction on the event-horizon scale with super resolution. The
      results demonstrate that our approximation reproduces the CVE values obtained via
      literally conducted cross-validation with reasonably good precision.

PMID- 29216216
TI  - Epidemiological and genetic characteristics of EV71 in hand, foot, and mouth
      disease in Guangxi, southern China, from 2010 to 2015.
AB  - Hand, foot, and mouth disease (HFMD) is a significant public health challenge in
      China. Human enterovirus 71 (EV71) is regarded as the predominant causative
      pathogen of HFMD. Since 2015, two inactivated EV71 vaccines have been approved in
      mainland China, and because their use could change the HFMD pathogen spectrum,
      this should now be monitored. However, the epidemiological and genetic trends of
      EV71 with respect to HFMD in Guangxi, southern China, are still not clear. In
      this study, we describe the epidemiological and genetic characterization of this
      virus in clinically-diagnosed HFMD reported from 2010 to 2015 in Guangxi. Data
      showed that a two-year epidemic cycle, with a predominance of EV71 infections,
      contributed to HFMD outbreaks in Guangxi. Furthermore, this virus is a major
      causative agent of severe and fatal HFMD. Interestingly, in Guangxi, EV71
      positive rates tended to decrease over time. In particular, EV71-positive rates
      were found in Fangchenggang city, which reported very few severe and fatal cases
      over the six-year period. Phylogenetic analysis of the VP1 gene revealed that the
      major circulating strains belonged exclusively to genotype C, subtype 4a (C4a),
      and most clustered with strains circulating in southern China. The most
      interesting finding was that a strain isolated in 2012 clustered with Vietnamese
      strains isolated from 2011-2012. The data highlight the importance of pathogen
      surveillance for HFMD in China, especially Guangxi, which is located on the
      border of China and the Association of Southeast Asian Nations.

PMID- 29216217
TI  - The emerging role of ASC in dendritic cell metabolism during Chlamydia infection.
AB  - Chlamydia trachomatis is a bacterial agent that causes sexually transmitted
      infections worldwide. The regulatory functions of dendritic cells (DCs) play a
      major role in protective immunity against Chlamydia infections. Here, we
      investigated the role of ASC in DCs metabolism and the regulation of DCs
      activation and function during Chlamydia infection. Following Chlamydia
      stimulation, maturation and antigen presenting functions were impaired in ASC-/-
      DCs compared to wild type (WT) DCs, in addition, ASC deficiency induced a
      tolerant phenotype in Chlamydia stimulated DCs. Using real-time extracellular
      flux analysis, we showed that activation in Chlamydia stimulated WT DCs is
      associated with a metabolic change in which mitochondrial oxidative
      phosphorylation (OXPHOS) is inhibited and the cells become committed to utilizing
      glucose through aerobic glycolysis for differentiation and antigen presenting
      functions. However, in ASC-/- DCs Chlamydia-induced metabolic change was
      prevented and there was a significant effect on mitochondrial morphology. The
      mitochondria of Chlamydia stimulated ASC-/- DCs had disrupted cristae compared to
      the normal narrow pleomorphic cristae found in stimulated WT DCs. In conclusion,
      our results suggest that Chlamydia-mediated activation of DCs is associated with
      a metabolic transition in which OXPHOS is inhibited, thereby dedicating the DCs
      to aerobic glycolysis, while ASC deficiency disrupts DCs function by inhibiting
      the reprogramming of DCs metabolism within the mitochondria, from glycolysis to
      electron transport chain.

PMID- 29216218
TI  - Stroke subtype classification by geometrical descriptors of lesion shape.
AB  - BACKGROUND AND PURPOSE: Inference of etiology from lesion pattern in acute
      magnetic resonance imaging is valuable for management and prognosis of acute
      stroke patients. This study aims to assess the value of three-dimensional
      geometrical lesion-shape descriptors for stroke-subtype classification,
      specifically regarding stroke of cardioembolic origin. METHODS: Stroke Etiology
      was classified according to ASCOD in retrospectively selected patients with acute
      stroke. Lesions were segmented on diffusion-weighed datasets, and descriptors of
      lesion shape quantified: surface area, sphericity, bounding box volume, and ratio
      between bounding box and lesion volume. Morphological measures were compared
      between stroke subtypes classified by ASCOD and between patients with embolic
      stroke of cardiac and non-cardiac source. RESULTS: 150 patients (mean age 77
      years; 95% CI, 65-80 years; median NIHSS 6, range 0-22) were included. Group
      comparison of lesion shape measures demonstrated that lesions caused by small
      vessel disease were smaller and more spherical compared to other stroke subtypes.
      No significant differences of morphological measures were detected between
      patients with cardioembolic and non-cardioembolic stroke. CONCLUSION: Stroke
      lesions caused by small vessel disease can be distinguished from other stroke
      lesions based on distinctive morphological properties. However, within the group
      of embolic strokes, etiology could not be inferred from the morphology measures
      studied in our analysis.

PMID- 29216219
TI  - Wrapped: An R package for circular data.
AB  - The Wrapped package computes the probability density function, cumulative
      distribution function, quantile function and also generates random samples for
      many univariate wrapped distributions. It also computes maximum likelihood
      estimates, standard errors, confidence intervals and measures of goodness of fit
      for nearly fifty univariate wrapped distributions. Numerical illustrations of the
      package are given.

PMID- 29216220
TI  - Retarded germination of Nicotiana tabacum seeds following insertion of exogenous
      DNA mimics the seed persistent behavior.
AB  - Tobacco seeds show a coat-imposed dormancy in which the seed envelope tissues
      (testa and endosperm) impose a physical constraint on the radicle protrusion. The
      germination-limiting process is represented by the endosperm rupture which is
      induced by cell-wall weakening. Transgenic tobacco seeds, obtained by insertion
      of exogenous genes codifying for seed-based oral vaccines (F18 and VT2eB), showed
      retarded germination with respect to the wild type and modified the expression of
      endogenous proteins. Morphological and proteomic analyses of wild type and
      transgenic seeds revealed new insights into factors influencing seed germination.
      Our data showed that the interference of exogenous DNA influences the germination
      rather than the dormancy release, by modifying the maturation process. Dry seeds
      of F18 and VT2eB transgenic lines accumulated a higher amount of reserve and
      stress-related proteins with respect to the wild type. Moreover, the storage
      proteins accumulated in tobacco F18 and VT2eB dry seeds have structural
      properties that do not enable the early limited proteolysis observed in the wild
      type. Morphological observations by electron and light microscopy revealed a
      retarded mobilization of the storage material from protein and lipid bodies in
      transgenic seeds, thus impairing water imbibition and embryo elongation. In
      addition, both F18 and VT2eB dry seeds are more rounded than the wild type. Both
      the morphological and biochemical characteristics of transgenic seeds mimic the
      seed persistent profile, in which their roundness enables them to be buried in
      the soil, while the higher content of storage material enables the hypocotyl to
      elongate more and the cotyledons to emerge.

PMID- 29216221
TI  - Copy number variants in Ebstein anomaly.
AB  - BACKGROUND: Ebstein anomaly (EA) is a rare congenital defect characterized by
      apical displacement of the septal tricuspid leaflets and atrialization of the
      right ventricle. The etiology of EA is unclear; however, recurrence in families
      and the association of EA with genetic syndromes and copy number variants (CNVs)
      suggest a genetic component. OBJECTIVE: We performed a population-based study to
      search for recurrent and novel CNVs in a previously unreported set of EA cases.
      METHODS: We genotyped 60 EA cases identified from all live births (2,891,076)
      from selected California counties (1991-2010) using the Illumina HumanOmni2.5-8
      array. We identified 38 candidate CNVs in 28 (46%) cases and prioritized and
      validated 11 CNVs based on the genes included. RESULTS: Five CNVs (41%)
      overlapped or were close to genes involved in early myocardial development,
      including NODAL, PDLIM5, SIX1, ASF1A and FGF12. We also replicated a previous
      association of EA with CNVs at 1p34.1 and AKAP12. Finally, we identified four
      CNVs overlapping or in close proximity to the transcription factors HES3, TRIM71,
      CUX1 and EIF4EBP2. CONCLUSIONS: This study supports the relationship of genetic
      factors to EA and demonstrates that defects in cardiomyocytes and myocardium
      differentiation may play a role. Abnormal differentiation of cardiomyocytes and
      how genetic factors contribute should be examined for their association with EA.

PMID- 29216222
TI  - Cortical computations via transient attractors.
AB  - The ability of sensory networks to transiently store information on the scale of
      seconds can confer many advantages in processing time-varying stimuli. How a
      network could store information on such intermediate time scales, between typical
      neurophysiological time scales and those of long-term memory, is typically
      attributed to persistent neural activity. An alternative mechanism which might
      allow for such information storage is through temporary modifications to the
      neural connectivity which decay on the same second-long time scale as the
      underlying memories. Earlier work that has explored this method has done so by
      emphasizing one attractor from a limited, pre-defined set. Here, we describe an
      alternative, a Transient Attractor network, which can learn any pattern presented
      to it, store several simultaneously, and robustly recall them on demand using
      targeted probes in a manner reminiscent of Hopfield networks. We hypothesize that
      such functionality could be usefully embedded within sensory cortex, and allow
      for a flexibly-gated short-term memory, as well as conferring the ability of the
      network to perform automatic de-noising, and separation of input signals into
      distinct perceptual objects. We demonstrate that the stored information can be
      refreshed to extend storage time, is not sensitive to noise in the system, and
      can be turned on or off by simple neuromodulation. The diverse capabilities of
      transient attractors, as well as their resemblance to many features observed in
      sensory cortex, suggest the possibility that their actions might underlie neural
      processing in many sensory areas.

PMID- 29216223
TI  - Increased risk of peripheral arterial occlusive disease in patients with Bell's
      palsy using population data.
AB  - OBJECTIVE: This population-based cohort study investigated the risk of developing
      peripheral arterial occlusive disease (PAOD) in patients with Bell's palsy.
      METHODS: We used longitudinal claims data of health insurance of Taiwan to
      identify 5,152 patients with Bell's palsy newly diagnosed in 2000-2010 and a
      control cohort of 20,608 patients without Bell's palsy matched by propensity
      score. Incidence and hazard ratio (HR) of PAOD were assessed by the end of 2013.
      RESULTS: The incidence of PAOD was approximately 1.5 times greater in the Bell's
      palsy group than in the non-Bell's palsy controls (7.75 vs. 4.99 per 1000 person
      years). The Cox proportional hazards regression analysis measured adjusted HR was
      1.54 (95% confidence interval (CI) = 1.35-1.76) for the Bell's palsy group
      compared to the non-Bell's palsy group, after adjusting for sex, age, occupation,
      income and comorbidities. Men were at higher risk of PAOD than women in the
      Bell's palsy group, but not in the controls. The incidence of PAOD increased with
      age in both groups, but the Bell's palsy group to control group HR of PAOD
      decreased as age increased. The systemic steroid treatment reduced 13% of PAOD
      hazard for Bell's palsy patients, compared to those without the treatment, but
      not significant. CONCLUSIONS: Bell's palsy appears to be associated with an
      increased risk of developing PAOD. Further pathophysiologic, histopathology and
      immunologic research is required to explore the underlying biologic mechanism.

PMID- 29216224
TI  - Cytotoxicity of portoamides in human cancer cells and analysis of the molecular
      mechanisms of action.
AB  - Portoamides are cyclic peptides produced and released by the cyanobacterial
      strain Phormidium sp. presumably to interfere with other organisms in their
      ecosystems ("allelopathy"). Portoamides were previously demonstrated to have an
      antiproliferative effect on human lung carcinoma cells, but the underlying
      mechanism of this activity has not been described. In the present work, the
      effects of portoamides on proliferation were examined in eight human cancer cell
      lines and two non-carcinogenic cell lines, and major differences in sensitivities
      were observed. To generate hypotheses with regard to molecular mechanisms of
      action, quantitative proteomics using 2D gel electrophoresis and MALDI-TOF/TOF
      were performed on the colon carcinoma cell line HT-29. The expression of proteins
      involved in energy metabolism (mitochondrial respiratory chain and pentose
      phosphate pathway) was found to be affected. The hypothesis of altered energy
      metabolism was tested in further experiments. Exposure to portoamides resulted in
      reduced cellular ATP content, likely due to decreased mitochondrial energy
      production. Mitochondrial hyperpolarization and reduced mitochondrial reductive
      capacity was observed in treated cells. Furthermore, alterations in the
      expression of peroxiredoxins (PRDX4, PRDX6) and components of proteasome subunits
      (PSB4, PSA6) were observed in portoamide-treated cells, but these alterations
      were not associated with detectable increases in oxidative stress. We conclude
      that the cytotoxic activity of portoamides is associated with disturbance of
      energy metabolism, and alterations in mitochondrial structure and function.

PMID- 29216225
TI  - Real-time visualization of thrombus formation at the interface between connectors
      and tubes in medical devices by using optical coherence tomography.
AB  - BACKGROUND: Blood-contacting devices have contributed to improving the treatment
      of patients. However, thrombus formation at the interface between a connector and
      tube is still a potential source of thrombus-related complications that induce
      stroke or myocardial infarction. We aimed to develop a non-blood-contacting real
      time method for visualizing thrombus formation, and to experimentally investigate
      the time-dependent phenomenon of thrombus formation at the interface between a
      connector and a tube in a medical device. METHODS AND FINDINGS: An optical
      coherence tomography device with a center wavelength of 1330 nm was used to
      visualize thrombus formation during porcine blood circulation for 50 min in a
      closed 50-mL circulation system isolated from ambient air. The thrombus formation
      sites at the interface between a tube and connector were visualized. The area of
      the thrombus formation at the interface between the inlet of the connector and
      the tube was found to be 0.012 +/- 0.011 mm2. Conversely, at the interface
      between the outlet of the connector and the tube, the area was found to be 0.637
      +/- 0.306 mm2. Thus, significantly larger amounts of thrombus were formed at the
      outlet interface (p < 0.01). The thrombus formation area at the outlet interface
      increased over time. Conversely, the area of thrombus formation showed repeated
      increasing and decreasing behavior at the inlet interface. Flow visualization
      with particle image velocimetry showed the presence of a flow separated area in
      the minimal flow phase at the inlet interface and a large recirculating slow flow
      region at the outlet interface in the minimal flow phase. These data suggested
      that the recirculating stagnant flow region contributed to thrombus growth.
      CONCLUSIONS: The method presented here was effective in quantitatively assessing
      time-dependent phenomena of thrombus formation at the connector-tube interface.
      The method may contribute to the assessment of thrombogenicity of a novel design
      of connector.

PMID- 29216226
TI  - Startling similarity: Effects of facial self-resemblance and familiarity on the
      processing of emotional faces.
AB  - Facial self-resemblance has been associated with positive emotional evaluations,
      but this effect may be biased by self-face familiarity. Here we report two
      experiments utilizing startle modulation to investigate how the processing of
      facial expressions of emotion is affected by subtle resemblance to the self as
      well as to familiar faces. Participants of the first experiment (I) (N = 39) were
      presented with morphed faces showing happy, neutral, and fearful expressions
      which were manipulated to resemble either their own or unknown faces. At SOAs of
      either 300 ms or 3500-4500 ms after picture onset, startle responses were
      elicited by binaural bursts of white noise (50 ms, 105 dB), and recorded at the
      orbicularis oculi via EMG. Manual reaction time was measured in a simple emotion
      discrimination paradigm. Pictures preceding noise bursts by short SOA inhibited
      startle (prepulse inhibition, PPI). Both affective modulation and PPI of startle
      in response to emotional faces was altered by physical similarity to the self. As
      indexed both by relative facilitation of startle and faster manual responses,
      self-resemblance apparently induced deeper processing of facial affect,
      particularly in happy faces. Experiment II (N = 54) produced similar findings
      using morphs of famous faces, yet showed no impact of mere familiarity on PPI
      effects (or response time, either). The results are discussed with respect to
      differential (presumably pre-attentive) effects of self-specific vs. familiar
      information in face processing.

PMID- 29216227
TI  - Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall
      survival and progression free survival in the Danish population.
AB  - Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis
      in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not
      been validated in an unselected population-based cohort. We analyzed 2558 newly
      diagnosed MM patients in the Danish Multiple Myeloma Registry representing the
      entire MM population in Denmark from 2005-2013. Two-thousand two hundred and
      fifty three patients (90%) presented with reduction below lower normal levels of
      at least one uninvolved immunoglobulin. Using multivariable Cox regression we
      found that high age, high ISS score, high LDH and IgA MM were associated to both
      shorter overall survival and progression free survival. Furthermore, bone marrow
      plasma cell % was associated to short progression free survival. Immunoparesis
      had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)).
      Likewise, the number of suppressed immunoglobulins or the relative degree of
      suppressed uninvolved immunoglobulins from lower normal level (quantitative
      immunoparesis) was not associated to OS in the multivariable analysis. However,
      quantitative immunoparesis with at least 25% reduction (from lower normal level)
      of uninvolved immunoglobulins was associated to shorter PFS for the entire
      population. The impact of quantitative immunoparesis on PFS was present
      irrespective of calendar periods 2005-2008 and 2009-2013. Our population-based
      study does not confirm that immunoparesis at diagnosis is an independent
      prognostic factor regarding OS. However, quantitative immunoparesis is associated
      to a shorter PFS.

PMID- 29216228
TI  - Primary prevention of myocardial infarction with angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers in hypertensive patients with
      rheumatoid arthritis-A nationwide cohort study.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is regarded as a high risk factor for
      myocardial infarction. Hypertension is a major modifiable risk factor
      contributing to increased risk of myocardial infarction (MI). Dual blood pressure
      (BP)-lowering and anti-inflammatory effect of renin-angiotensin-system (RAS)
      inhibitors may possess protective effect from MI in RA population. However,
      treatment of hypertension with RAS inhibitors and MI in RA population remains
      unclear. METHODS: We investigated whether RAS blockade could decrease risk of
      incident MI in hypertensive patients with RA. We identified patients with RA and
      hypertension from the Registry for Catastrophic Illness, a nation-wide database
      encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The
      primary endpoint was MI and the median duration of follow up was 2,986 days.
      Propensity score weighting and Cox proportional hazards regression models were
      used to estimate hazard ratios for MI. RESULTS: Among 27,335 subjects, 9.9%
      received angiotensin-converting enzyme inhibitors (ACEIs), 25.9% received
      angiotensin II receptor blockers (ARBs) and 20.0% received ACEIs or ARBs
      alternatively. The incidence of MI significantly decreased in patients treated
      with ACEIs (hazard ratio 0.707; 95% confidence interval 0.595-0.840), ARBs
      (0.641; 0.550-0.747) and ACEIs/ARBs (0.631; 0.539-0.739). The protective effect
      of ACEI or ARB therapy was significantly better in patients taking longer
      duration. The effect remained robust in subgroup analyses. CONCLUSIONS: Therapy
      of ACEIs or ARBs is associated with a lower risk of MI among patients with RA.
      Hence, hypertension in patients with RA could comprise a compelling indication
      for RAS inhibitors.

PMID- 29216229
TI  - Factors associated with pre-diabetes in Tehranian men and women: A structural
      equations modeling.
AB  - OBJECTIVE: To examine associations of sex-specific related factors with pre
      diabetes in Tehranian non-diabetic adults. METHODS: This study has been conducted
      within the framework of the Tehran Lipid and Glucose Study (TLGS) between 2008
      2010. A total of 5568 (55.4% female) non-diabetic adults, aged >=20 years,
      selected from among participants of the TLGS, were recruited for the study. Data
      on socio-behavioral factors, family history of diabetes and cardio-metabolic risk
      factors were included in the hypothesized model to test their direct and indirect
      associations with pre-diabetes in men and women separately, using structural
      equation modeling. RESULTS: Pre-diabetes was diagnosed in 23.6% of participants,
      with significantly higher prevalence in men compared to women (27.4% and 20.5%,
      respectively; p<0.001). Body mass index (BMI) and triglycerides (TG) in both
      sexes and hypertension and high density lipoprotein only in women, were directly
      associated with pre-diabetes (p<0.05). Poor diet in women was the only behavioral
      factor directly associated with pre-diabetes (p<0.05). Age in both sexes and
      education, only in women, were directly associated with pre-diabetes. In both
      genders, age, marital status, education, employment, poor diet and leisure time
      physical activity were indirectly associated with pre-diabetes through cardio
      metabolic risk factors. CONCLUSIONS: The main modifiable factors directly
      associated with pre-diabetes were TG in women and BMI in men, which need to be
      prioritized in health policies for diabetes prevention programs in Tehranian
      adults. Future research should focus on the gender-specific determinants and
      underlying mechanisms for TG levels and BMI status among this population.

PMID- 29216230
TI  - A comprehensive scoring system in correlation with perioperative airway
      management for neonatal Pierre Robin Sequence.
AB  - PURPOSE: To evaluate a comprehensive scoring system which combines clinical
      manifestations of Pierre Robin Sequence (PRS) including severity of breathing
      difficulties, body weight and preoperative Cormack-Lehane grade, for its
      correlation with perioperative PRS airway management decision. DESIGN: Forty PRS
      children were retrospectively recruited after surgery. Specialists examined all
      subjects and scored for clinical manifestations (1' - 4'), weight gain (1'- 4'),
      dyspnea scores (1'- 4'), and Cormack-Lehane grade (1'- 4'). The correlation of
      the integrated scores and the necessity of endotracheal intubation or laryngeal
      mask application were analyzed. In addition, the score correlation with
      postoperative dyspnea and/or low pulse oxygen saturation (SPO2) levels after
      extubation was determined. FINDINGS: In our study every individual patient had a
      score from 0' to 16', while the higher in the numbers represented higher risk of
      breathing difficulty. All patients with comprehensive scores <10 points underwent
      endotracheal intubation successfully. Patients scoring 10-12 points had an
      intubation success rate of 47%, whereas all patients scored >13 points required a
      laryngeal mask assisted airway management and were considered to have difficult
      airways. Dyspnea after extubation and postoperative low SPO2 occurred among
      patients who scored over 10 points. CONCLUSION: In PRS patients, preoperative
      weight gaining status and severity of dyspnea in combination with Cormack-Lehane
      classification provide a scoring system that could help to optimize airway
      management decisions such as endotracheal intubation or laryngeal mask airway
      placement and has the potential to predict postoperative dyspnea or low SPO2
      levels.

PMID- 29216231
TI  - A computational model to investigate the effect of pennation angle on surface
      electromyogram of Tibialis Anterior.
AB  - This study has described and experimentally validated the differential electrodes
      surface electromyography (sEMG) model for tibialis anterior muscles during
      isometric contraction. This model has investigated the effect of pennation angle
      on the simulated sEMG signal. The results show that there is no significant
      effect of pennation angle in the range 0 degrees  to 20 degrees  to the single
      fibre action potential shape recorded on the skin surface. However, the changes
      with respect to pennation angle are observed in sEMG amplitude, frequency and
      fractal dimension. It is also observed that at different levels of muscle
      contractions there is similarity in the relationships with Root Mean Square,
      Median Frequency, and Fractal Dimension of the recorded and simulated sEMG
      signals.

PMID- 29216233
TI  - Parental absence predicts suicide ideation through emotional disorders.
AB  - The objectives of the study were to investigate the association between the
      parental absence and suicide ideation and to examine the roles of emotional
      disorders in the aforementioned relationship. Four thousand five hundred and
      thirteen children from rural areas in Jiangsu Province, China, participated in
      the study. Among the participants, 2416 were non-left-behind children (children
      living with both parents) and 1997 were left-behind children (children living
      with the absence of at least one parent). All participants responded to the
      Center for Epidemiological Studies Depression Scale for Children, the
      Multidimensional Anxiety Scale for Children, and a question regarding
      respondents' suicide ideation. Results indicated that as compared with non-left
      behind children, the left-behind children with both-parents absence were
      statistically more likely to show suicide ideation. Furthermore, all the three
      types parental absence-father absence, mother absence, and both-parents absence
      were significantly associated with negative emotional outcomes. Moreover,
      depression, social anxiety, and physical anxiety were shown to be significant
      mediators in the relationship of parental absence and suicide ideation of
      children. The stress of parental absence and its negative impact on children's
      mental health are discussed.

PMID- 29216232
TI  - Indole at low concentration helps exponentially growing Escherichia coli survive
      at high temperature.
AB  - A culture of stationary phase Escherichia coli cells has been reported to produce
      copious indole when exposed to high temperature (50 degrees C), and this response
      has been proposed to aid survival. We reinvestigated this phenomenon and found
      that indole production under these conditions is probably not a direct response
      to heat stress. Rather, E. coli produces indole when growth is prevented,
      irrespective of whether this is due to heat stress, antibiotic treatment or the
      removal of nutrients. Moreover, 300MUM indole produced at 50 degrees C does not
      improve the viability of heat stressed cells. Interestingly, a much lower
      concentration of indole (20 MUM) improves the survival of an indole-negative
      strain (DeltatnaA) when heat stressed during exponential growth. In addition we
      have shown that the distribution of tryptophanase, the enzyme responsible for
      indole synthesis, is highly heterogeneous among cells in a population, except
      during the transition between exponential and stationary phases. The observation
      that, despite the presence of the tryptophanase, very little indole is produced
      during early exponential phase suggests that there is post-translational
      regulation of the enzyme.

PMID- 29216234
TI  - Infant and dyadic assessment in early community-based screening for autism
      spectrum disorder with the PREAUT grid.
AB  - BACKGROUND: The need for early treatment of autism spectrum disorders (ASD)
      necessitates early screening. Very few tools have been prospectively tested with
      infants of less than 12 months of age. The PREAUT grid is based on dyadic
      assessment through interaction and shared emotion and showed good metrics for
      predicting ASD in very-high-risk infants with West syndrome. METHODS: We assessed
      the ability of the PREAUT grid to predict ASD in low-risk individuals by
      prospectively following and screening 12,179 infants with the PREAUT grid at four
      (PREAUT-4) and nine (PREAUT-9) months of age. A sample of 4,835 toddlers
      completed the Checklist for Autism in Toddlers (CHAT) at 24 months (CHAT-24) of
      age. Children who were positive at one screening (N = 100) were proposed a
      clinical assessment (including the Children Autism Rating Scale, a Developmental
      Quotient, and an ICD-10-based clinical diagnosis if appropriate) in the third
      year of life. A randomly selected sample of 1,100 individuals who were negative
      at all screenings was followed by the PMI team from three to five years of age to
      identify prospective false negative cases. The clinical outcome was available for
      45% (N = 45) of positive children and 52.6% (N = 579) of negative children.
      RESULTS: Of the 100 children who screened positive, 45 received a diagnosis at
      follow-up. Among those receiving a diagnosis, 22 were healthy, 10 were diagnosed
      with ASD, seven with intellectual disability (ID), and six had another
      developmental disorder. Thus, 50% of infants positive at one screening
      subsequently received a neurodevelopmental diagnosis. The PREAUT grid scores were
      significantly associated with medium and high ASD risk status on the CHAT at 24
      months (odds ratio of 12.1 (95%CI: 3.0-36.8), p < 0.001, at four months and 38.1
      (95%CI: 3.65-220.3), p < 0.001, at nine months). Sensitivity (Se), specificity,
      negative predictive values, and positive predictive values (PPVs) for PREAUT at
      four or nine months, and CHAT at 24 months, were similar [PREAUT-4: Se = 16.0 to
      20.6%, PPV = 25.4 to 26.3%; PREAUT-9: Se = 30.5 to 41.2%, PPV = 20.2 to 36.4%;
      and CHAT-24: Se = 33.9 to 41.5%, PPV = 27.3 to 25.9%]. The repeated use of the
      screening instruments increased the Se but not PPV estimates [PREAUT and CHAT
      combined: Se = 67.9 to 77.7%, PPV = 19.0 to 28.0%]. CONCLUSIONS: The PREAUT grid
      can contribute to very early detection of ASD and its combination with the CHAT
      may improve the early diagnosis of ASD and other neurodevelopmental disorders.

PMID- 29216236
TI  - Aggregated responses of human mobility to severe winter storms: An empirical
      study.
AB  - Increasing frequency of extreme winter storms has resulted in costly damages and
      a disruptive impact on the northeastern United States. It is important to
      understand human mobility patterns during such storms for disaster preparation
      and relief operations. We investigated the effects of severe winter storms on
      human mobility during a 2015 blizzard using 2.69 million Twitter geolocations. We
      found that displacements of different trip distances and radii of gyration of
      individuals' mobility were perturbed significantly. We further explored the
      characteristics of perturbed mobility during the storm, and demonstrated that
      individuals' recurrent mobility does not have a higher degree of similarity with
      their perturbed mobility, when comparing with its similarity to non-perturbed
      mobility. These empirical findings on human mobility impacted by severe winter
      storms have potential long-term implications on emergency response planning and
      the development of strategies to improve resilience in severe winter storms.

PMID- 29216235
TI  - Association between memory impairment and brain metabolite concentrations in
      North Korean refugees with posttraumatic stress disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous
      psychological stress that can result in neurocognitive and neurochemical changes.
      To date, the causal relationship between them remains unclear. The present study
      is to investigate the association between neurocognitive characteristics and
      neural metabolite concentrations in North Korean refugees with PTSD. A total of
      53 North Korean refugees with or without PTSD underwent neurocognitive function
      tests. For neural metabolite scanning, magnetic resonance spectroscopy of the
      hippocampus and anterior cingulate cortex (ACC) has been conducted. We assessed
      between-group differences in neurocognitive test scores and metabolite levels.
      Additionally, a multiple regression analysis was carried out to evaluate the
      association between neurocognitive function and metabolite levels in patients
      with PTSD. Memory function, but not other neurocognitive functions, was
      significantly lower in the PTSD group compared with the non-PTSD group.
      Hippocampal N-acetylaspartate (NAA) levels were not different between groups;
      however, NAA levels were significantly lower in the ACC of the PTSD group than
      the non-PTSD group (t = 2.424, p = 0.019). The multiple regression analysis
      showed a negative association between hippocampal NAA levels and delayed recall
      score on the auditory verbal learning test (beta = -1.744, p = 0.011) in the non
      PTSD group, but not in the PTSD group. We identified specific memory impairment
      and the role of NAA levels in PTSD. Our findings suggest that hippocampal NAA has
      a protective role in memory impairment and development of PTSD after exposure to
      traumatic events.

PMID- 29216237
TI  - The nutraceutical benefits of subfractions of Abelmoschus esculentus in treating
      type 2 diabetes mellitus.
AB  - Abelmoschus esculentus (AE), a commonly consumed vegetable, is well-known for its
      anti-hyperglycemic effects. However, few scientific reports have identified its
      targets because mucilage increases the difficulty of manipulation. We recently
      reported extraction steps to obtain subfractions of AE, which were found to
      attenuate the adverse effects of high glucose and fatty acid in vitro. In this
      study, we used modified extraction steps and type 2 diabetic rats to explore
      whether AE subfractions can improve the metabolic disturbances caused by insulin
      resistance in vivo. AE subfractions (F1, F2, and FR) were prepared. The type 2
      diabetes model was induced by feeding male Sprague-Dawley rats with a high-fat
      diet and injecting them with 35 mg/kgbw streptozotocin when their body weight
      reached 475 +/- 15 g. After a hyperglycemic status had been confirmed, the rats
      were tube-fed with or without different doses of AE subfractions. Serum glucose,
      lipid markers, insulin, HbA1c and HOMA-IR were measured in the following 12
      weeks. Serum glucose promptly increased and insulin resistance was noted in the
      diabetic rats (glucose: 360-500 mg/dl, HOMA-IR 9.8-13.8). F2, rich in
      polysaccharides and carbohydrates, was most effective in attenuating
      hyperglycemia and insulin resistance (glucose: 200 mg/dl; HOMA-IR: 5.3) and
      especially HbA1C (from 8.0% to 6.5%). All of the AE subfractions lowered the
      level of triglycerides and free fatty acid, but not the level of total
      cholesterol. FR significantly increased the high-density lipoprotein/low-density
      lipoprotein ratio, indicating its benefits for lipoprotein profiles. While F2 and
      FR were associated with weight gain, F1 possessed an anti-obese effect. In
      conclusion, whether it is consumed as a vegetable or as a nutraceutical, AE has
      the potential to be an adjuvant therapy for diabetes. AE subfractions could be
      developed individually and deserve further investigation.

PMID- 29216238
TI  - Mother-infant interaction assessment at discharge and at 6 months in a French
      cohort of infants born very preterm: The OLIMPE study.
AB  - OBJECTIVES: The principal aim was to investigate the feasibility of assessing
      mother-infant interactions at discharge and at 6 months infant corrected age in
      singletons born before 32 weeks of gestation. The secondary aims were to describe
      these interactions and their disorders, explore the association between maternal
      emotional state and the interactions, and assess the relationship between
      disordered interactions and infant social withdrawal behaviour. METHODS: OLIMPE
      is an ancillary study of the population-based study EPIPAGE 2, which recruited
      preterm neonates in France in 2011. 163 dyads participated at discharge and 148
      at 6 months. Interactions were observed with the Attachment During Stress (ADS)
      scale, which includes two behavioural subscales, for the mother (m-ADS) and her
      infant (i-ADS). Two professionals independently completed the ADS scales for one
      third of the observations. Maternal emotional state was assessed using self
      administered questionnaires of depression, anxiety, and stress. Infant's social
      withdrawal behaviour at 6 months was measured by the Alarm Distress Baby scale.
      RESULTS: At discharge, 15.3% of the m-ADS scales and 43.3% of the i-ADS scales
      had at least one unobserved component. At 6 months, all items on both scales were
      noticeable in >90% of the dyads. Reliability, estimated by the kappa coefficient,
      ranged between 0.39 and 0.76 at discharge, and between 0.21 and 0.69 at 6 months.
      Disordered interactions were indicated on 48.6% of the m-ADS scales and 36.5% of
      the i-ADS scales at discharge. At 6 months, these rates were 32.6% and 26.0%.
      Disordered interactions at 6 months were associated with identified disorder at
      discharge. Insecure infant attachment was not influenced by maternal mental
      health but was strongly associated with infant social withdrawal behaviour.
      CONCLUSIONS: The ADS scale can be used to screen for early interaction disorders
      after premature birth and may help to target dyads that would most benefit from
      early intervention.

PMID- 29216239
TI  - Effects of early afterdepolarizations on excitation patterns in an accurate model
      of the human ventricles.
AB  - Early Afterdepolarizations, EADs, are defined as the reversal of the action
      potential before completion of the repolarization phase, which can result in
      ectopic beats. However, the series of mechanisms of EADs leading to these ectopic
      beats and related cardiac arrhythmias are not well understood. Therefore, we
      aimed to investigate the influence of this single cell behavior on the whole
      heart level. For this study we used a modified version of the Ten Tusscher
      Panfilov model of human ventricular cells (TP06) which we implemented in a 3D
      ventricle model including realistic fiber orientations. To increase the
      likelihood of EAD formation at the single cell level, we reduced the
      repolarization reserve (RR) by reducing the rapid delayed rectifier Potassium
      current and raising the L-type Calcium current. Varying these parameters defined
      a 2D parametric space where different excitation patterns could be classified.
      Depending on the initial conditions, by either exciting the ventricles with a
      spiral formation or burst pacing protocol, we found multiple different spatio
      temporal excitation patterns. The spiral formation protocol resulted in the
      categorization of a stable spiral (S), a meandering spiral (MS), a spiral break
      up regime (SB), spiral fibrillation type B (B), spiral fibrillation type A (A)
      and an oscillatory excitation type (O). The last three patterns are a 3D
      generalization of previously found patterns in 2D. First, the spiral fibrillation
      type B showed waves determined by a chaotic bi-excitable regime, i.e. mediated by
      both Sodium and Calcium waves at the same time and in same tissue settings. In
      the parameter region governed by the B pattern, single cells were able to
      repolarize completely and different (spiral) waves chaotically burst into each
      other without finishing a 360 degree rotation. Second, spiral fibrillation type A
      patterns consisted of multiple small rotating spirals. Single cells failed to
      repolarize to the resting membrane potential hence prohibiting the Sodium channel
      gates to recover. Accordingly, we found that Calcium waves mediated these
      patterns. Third, a further reduction of the RR resulted in a more exotic
      parameter regime whereby the individual cells behaved independently as
      oscillators. The patterns arose due to a phase-shift of different oscillators as
      disconnection of the cells resulted in continuation of the patterns. For all
      patterns, we computed realistic 9 lead ECGs by including a torso model. The B and
      A type pattern exposed the behavior of Ventricular Tachycardia (VT). We conclude
      that EADs at the single cell level can result in different types of cardiac
      fibrillation at the tissue and 3D ventricle level.

PMID- 29216240
TI  - The factor structure and construct validity of the inventory of callous
      unemotional traits in Chinese undergraduate students.
AB  - The current study assesses the factor structure and construct validity of the
      self-reported Inventory of Callous-Unemotional Traits (ICU) in 637 Chinese
      community adults (mean age = 25.98, SD = 5.79). A series of theoretical models
      proposed in previous studies were tested through confirmatory factor analyses.
      Results indicated that a shortened form that consists of 11 items (ICU-11) to
      assess callousness and uncaring factors has excellent overall fit. Additionally,
      correlations with a wide range of external variables demonstrated that this
      shortened form has similar construct validity compared to the original ICU. In
      conclusion, our findings suggest that the ICU-11 may be a promising self-report
      tool that could be a good substitute for the original form to assess callous
      uncaring traits in adults.

PMID- 29216241
TI  - Discussion about different cut-off values of conventional hamstring-to-quadriceps
      ratio used in hamstring injury prediction among professional male football
      players.
AB  - OBJECTIVE: To measure the sensitivity and specificity of differences cut-off
      values for isokinetic Hcon/Qcon ratio in order to improve the capacity to
      evaluate (retrospectively) the injury of hamstring muscles in professional soccer
      screened with knee isokinetic tests. DESIGN: Retrospective study. METHODS:
      Medical and biomechanical data of professional football players playing for the
      same team for at least one season between 2010 and 2016 were analysed. Hamstring
      strain injury cases and the reports generated via isokinetic testing were
      investigated. Isokinetic concentric(con) hamstring(H) and quadriceps(Q) absolute
      strength in addition with Hcon/Qcon ratio were examined for the injured versus
      uninjured limbs among injured players, and for the injured and non-injured
      players. 2 x 2 contingency table was used for comparing variables: predicted
      injured or predicted uninjured with actual injured or actual uninjured.
      Sensitivity, specificity, accuracy, positive and negative predictive values, and
      positive and negative likelihood ratio were calculated for three different cut
      off values (0.47 vs. 0.6 vs. 0.658) to compare the discriminative power of an
      isokinetic test, whilst examining the key value of Hcon/Qcon ratio which may
      indicate the highest level of ability to predispose a player to injury. McNemar's
      chi2 test with Yates's correction was used to determine agreement between the
      tests. PQStat software was used for all statistical analysis, and an alpha level
      of p <0.05 was used for all statistical comparisons. RESULTS: 340 isokinetic test
      reports on both limbs of 66 professional soccer players were analysed. Eleven
      players suffered hamstring injuries during the analysed period. None of these
      players sustained recurrence of hamstring injury. One player sustained hamstring
      strain injury on both legs, thus the total number of injuries was 12. Application
      of different cut-off values for Hcon/Qcon significantly affected the sensitivity
      and specificity of isokinetic test used as a tool for muscle injury detection.
      The use of 0.47 of Hcon/Qcon as a discriminate value resulted in significantly
      lower sensitivity when compared to 0.658 threshold (sensitivity of 16.7% vs.
      91.7%, respectively; t = 6.125,p = 0.0133). Calculated values of specificity
      (when three different cut-off were applied) were also significantly different.
      Threshold of 0.6 of Hcon/Qcon resulted with significantly lower specificity
      compared to 0.47 value (specificity of 46.9% vs. 94.5%, respectively; t =
      153.0,p<0.0001), and significantly higher specificity when compared to 0.658
      (specificity of 46.9% vs. 24.1%, respectively; t = 229.0, p<0.0001). CONCLUSION:
      The use of different cut-off values for Hcon/Qcon significantly affected the
      sensitivity and specificity of isokinetic testing. The interpretation of
      usefulness of isokinetic test as a screening tool in a group of male professional
      football players to predict hamstring injury occurrence within the next 12 months
      might be therefore significantly biased due to the different threshold values of
      Hcon/Qcon. Using one "normative" value as a cut-off (e.g. 0.47 or 0.60, or 0.658)
      to quantify soccer players (or not) to the group with a higher risk of knee
      injury might result in biased outcomes due to the natural strength asymmetry that
      is observed within the group of soccer players.

PMID- 29216242
TI  - The OxyR-regulated phnW gene encoding 2-aminoethylphosphonate:pyruvate
      aminotransferase helps protect Pseudomonas aeruginosa from tert-butyl
      hydroperoxide.
AB  - The LysR member of bacterial transactivators, OxyR, governs transcription of
      genes involved in the response to H2O2 and organic (alkyl) hydroperoxides (AHP)
      in the Gram-negative pathogen, Pseudomonas aeruginosa. We have previously shown
      that organisms lacking OxyR are rapidly killed by <2 or 500 mM H2O2 in planktonic
      and biofilm bacteria, respectively. In this study, we first employed a
      bioinformatic approach to elucidate the potential regulatory breadth of OxyR by
      scanning the entire P. aeruginosa PAO1 genome for canonical OxyR promoter
      recognition sequences (ATAG-N7-CTAT-N7-ATAG-N7-CTAT). Of >100 potential OxyR
      controlled genes, 40 were strategically selected that were not predicted to be
      involved in the direct response to oxidative stress (e.g., catalase, peroxidase,
      etc.) and screened such genes by RT-PCR analysis for potentially positive or
      negative control by OxyR. Differences were found in 7 of 40 genes when comparing
      an oxyR mutant vs. PAO1 expression that was confirmed by beta-galactosidase
      reporter assays. Among these, phnW, encoding 2-aminoethylphosphonate:pyruvate
      aminotransferase, exhibited reduced expression in the oxyR mutant compared to
      wild-type bacteria. Electrophoretic mobility shift assays indicated binding of
      OxyR to the phnW promoter and DNase I footprinting analysis also revealed the
      sequences to which OxyR bound. Interestingly, a phnW mutant was more susceptible
      to t-butyl-hydroperoxide (t-BOOH) treatment than wild-type bacteria. Although we
      were unable to define the direct mechanism underlying this phenomenon, we believe
      that this may be due to a reduced efficiency for this strain to degrade t-BOOH
      relative to wild-type organisms because of modulation of AHP gene transcription
      in the phnW mutant.

PMID- 29216244
TI  - Optimizing household survey methods to monitor the Sustainable Development Goals
      targets 6.1 and 6.2 on drinking water, sanitation and hygiene: A mixed-methods
      field-test in Belize.
AB  - BACKGROUND: The Sustainable Development Goals (SDGs) require household survey
      programmes such as the UNICEF-supported Multiple Indicator Cluster Surveys (MICS)
      to enhance data collection to cover new indicators. This study aims to evaluated
      methods for assessing water quality, water availability, emptying of sanitation
      facilities, menstrual hygiene management and the acceptability of water quality
      testing in households which are key to monitoring SDG targets 6.1 and 6.2 on
      drinking Water, Sanitation and Hygiene (WASH) and emerging issues. METHODS: As
      part of a MICS field test, we interviewed 429 households and 267 women age 15-49
      in Stann Creek, Belize in a split-sample experiment. In a concurrent qualitative
      component, we conducted focus groups with interviewers and cognitive interviews
      with respondents during and immediately following questionnaire administration in
      the field to explore their question comprehension and response processes.
      FINDINGS: About 88% of respondents agreed to water quality testing but also
      desired test results, given the potential implications for their own health.
      Escherichia coli was present in 36% of drinking water collected at the source,
      and in 47% of samples consumed in the household. Both questions on water
      availability necessitated probing by interviewers. About one quarter of
      households reported emptying of pit latrines and septic tanks, though one-quarter
      could not provide an answer to the question. Asking questions on menstrual
      hygiene was acceptable to respondents, but required some clarification and
      probing. CONCLUSIONS: In the context of Belize, this study confirmed the
      feasibility of collecting information on the availability and quality of drinking
      water, emptying of sanitation facilities and menstrual hygiene in a multi-purpose
      household survey, indicating specific areas to improve question formulation and
      field protocols. Improvements have been incorporated into the latest round of
      MICS surveys which will be a major source of national data for monitoring of SDG
      targets for drinking water, sanitation and hygiene and emerging issues for WASH
      sector programming.

PMID- 29216243
TI  - The obesity paradox and incident cardiovascular disease: A population-based
      study.
AB  - BACKGROUND: Prior work suggests that obesity may confer a survival advantage
      among persons with cardiovascular disease (CVD). This obesity "paradox" is
      frequently studied in the context of prevalent disease, a stage in the disease
      process when confounding from illness-related weight loss and selective survival
      are especially problematic. Our objective was to examine the association of
      obesity with mortality among persons with incident CVD, where biases are
      potentially reduced, and to compare these findings with those based on prevalent
      disease. METHODS: We used data from the Health and Retirement Study, an ongoing,
      nationally representative longitudinal survey of U.S. adults age 50 years and
      older initiated in 1992 and linked to Medicare claims. Cox proportional hazard
      models were used to estimate the association between weight status and mortality
      among persons with specific CVD diagnoses. CVD diagnoses were established by self
      reported survey data as well as Medicare claims. Prevalent disease models used
      concurrent weight status, and incident disease models used pre-diagnosis weight
      status. RESULTS: We examined myocardial infarction, congestive heart failure,
      stroke, and ischemic heart disease. A strong and significant obesity paradox was
      consistently observed in prevalent disease models (hazard of death 18-36% lower
      for obese class I relative to normal weight), replicating prior findings.
      However, in incident disease models of the same conditions in the same dataset,
      there was no evidence of this survival benefit. Findings from models using survey
      vs. claims-based diagnoses were largely consistent. CONCLUSION: We observed an
      obesity paradox in prevalent CVD, replicating prior findings in a population
      based sample with longer-term follow-up. In incident CVD, however, we did not
      find evidence of a survival advantage for obesity. Our findings do not offer
      support for reevaluating clinical and public health guidelines in pursuit of a
      potential obesity paradox.

PMID- 29216245
TI  - Robustness of rigid and adaptive networks to species loss.
AB  - Controversies in the complexity-stability debate have been attributed to the
      methodologies used such as topological vs. dynamical approaches or rigid vs.
      adaptive foraging behaviour of species. Here, we use a bipartite network model
      that incorporates both topological and population dynamics to investigate the
      robustness of 60 real ecological networks to the loss of generalist and
      specialist species. We compare the response in both adaptive and rigid networks.
      Our results show that the removal of generalists leads to the most secondary
      extinctions, implying that conservation strategies should aim to protect
      generalist species in the ecosystem. We also show that adaptive behaviour renders
      networks vulnerable to species loss at initial stages but enhances long term
      stability of the system. However, whether adaptive networks are more robust to
      species loss than rigid ones depends on the structure of the network.
      Specifically, adaptive networks with modularity < 0.3 are more robust than rigid
      networks of the same modularity. Interestingly, the more modular a network is,
      the less robust it is to external perturbations.

PMID- 29216246
TI  - Draft genome sequence of Actinotignum schaalii DSM 15541T: Genetic insights into
      the lifestyle, cell fitness and virulence.
AB  - The permanent draft genome sequence of Actinotignum schaalii DSM 15541T is
      presented. The annotated genome includes 2,130,987 bp, with 1777 protein-coding
      and 58 rRNA-coding genes. Genome sequence analysis revealed absence of genes
      encoding for: components of the PTS systems, enzymes of the TCA cycle, glyoxylate
      shunt and gluconeogensis. Genomic data revealed that A. schaalii is able to
      oxidize carbohydrates via glycolysis, the nonoxidative pentose phosphate and the
      Entner-Doudoroff pathways. Besides, the genome harbors genes encoding for enzymes
      involved in the conversion of pyruvate to lactate, acetate and ethanol, which are
      found to be the end products of carbohydrate fermentation. The genome contained
      the gene encoding Type I fatty acid synthase required for de novo FAS
      biosynthesis. The plsY and plsX genes encoding the acyltransferases necessary for
      phosphatidic acid biosynthesis were absent from the genome. The genome harbors
      genes encoding enzymes responsible for isoprene biosynthesis via the mevalonate
      (MVA) pathway. Genes encoding enzymes that confer resistance to reactive oxygen
      species (ROS) were identified. In addition, A. schaalii harbors genes that
      protect the genome against viral infections. These include restriction
      modification (RM) systems, type II toxin-antitoxin (TA), CRISPR-Cas and abortive
      infection system. A. schaalii genome also encodes several virulence factors that
      contribute to adhesion and internalization of this pathogen such as the tad genes
      encoding proteins required for pili assembly, the nanI gene encoding exo-alpha
      sialidase, genes encoding heat shock proteins and genes encoding type VII
      secretion system. These features are consistent with anaerobic and pathogenic
      lifestyles. Finally, resistance to ciprofloxacin occurs by mutation in
      chromosomal genes that encode the subunits of DNA-gyrase (GyrA) and topisomerase
      IV (ParC) enzymes, while resistant to metronidazole was due to the frxA gene,
      which encodes NADPH-flavin oxidoreductase.

PMID- 29216247
TI  - The glycoprotein of vesicular stomatitis virus promotes release of virus-like
      particles from tetherin-positive cells.
AB  - Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the
      interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317).
      However, several viruses encode tetherin antagonists and it is at present unknown
      whether residual VSV spread in tetherin-positive cells is also promoted by a
      virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV
      G) antagonizes tetherin in transfected cells, although with reduced efficiency as
      compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration
      of tetherin expression and was partially dependent on a GXXXG motif in the
      transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not
      modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as
      a tetherin antagonist in transfected cells but fail to provide evidence for a
      contribution of tetherin antagonism to viral spread.

PMID- 29216248
TI  - Effect of land-use changes on the abundance, distribution, and host-seeking
      behavior of Aedes arbovirus vectors in oil palm-dominated landscapes,
      southeastern Cote d'Ivoire.
AB  - BACKGROUND: Identifying priority areas for vector control is of considerable
      public health relevance. Arthropod-borne viruses (arboviruses) spread by Aedes
      mosquitoes are (re)emerging in many parts of the tropics, partially explained by
      changes in agricultural land-use. We explored the effects of land-use changes on
      the abundance, distribution, and host-seeking behavior of Aedes mosquitoes along
      a gradient of anthropogenic disturbance in oil palm-dominated landscapes in
      southeastern Cote d'Ivoire. METHODOLOGY: Between January and December 2014, eggs,
      larvae, pupae, and adults of Aedes mosquitoes were sampled in four types of
      macrohabitats (rainforest, polyculture, oil palm monoculture, and rural housing
      areas), using standard procedures (bamboo-ovitraps, metallic-ovitraps, larval
      surveys, and human-baited double-net traps). Immature stages were reared and
      adult mosquitoes identified at species level. PRINCIPAL FINDINGS: A total of
      28,276 Aedes specimens belonging to 11 species were collected. No Aedes-positive
      microhabitat and only four specimens of Ae. aegypti were found in oil palm
      monoculture. The highest abundance of Aedes mosquitoes (60.9%) was found in
      polyculture, while the highest species richness (11 species) was observed in
      rainforest. Ae. aegypti was the predominant Aedes species, and exhibited high
      anthropophilic behavior inflicting 93.0% of total biting to humans. The biting
      rate of Aedes mosquitoes was 34.6 and 7.2-fold higher in polyculture and rural
      housing areas, respectively, compared to rainforest. Three species (Ae. aegypti,
      Ae. dendrophilus, and Ae. vittatus) bit humans in polyculture and rural housing
      areas, with respective biting rates of 21.48 and 4.48 females/person/day.
      Unexpectedly, all three species were also feeding during darkness. Aedes females
      showed bimodal daily feeding cycles with peaks at around 08:00 a.m. and 05:00
      p.m. Host-seeking activities were interrupted between 11:00 a.m. and 02:00 p.m.
      in rural housing areas, while no such interruption was observed in polyculture.
      Some rainforest-dwelling Aedes species displayed little preference to feed on
      humans. CONCLUSIONS: In southeastern Cote d'Ivoire, the agricultural land
      use/land-cover changes due to the conversion of rainforest into oil palm
      monocultures influence the abundance, distribution, and host-seeking behaviors of
      anthropophagic and non-anthropophagic Aedes vectors. As a result, there is higher
      risk of humans to arbovirus transmission in polyculture and rural housing areas.
      There is a need for integrated vector management, including landscape
      epidemiology and ecotope-based vector control.

PMID- 29216249
TI  - Longer time to peak glucose during the oral glucose tolerance test increases
      cardiovascular risk score and diabetes prevalence.
AB  - INTRODUCTION: The pattern of glucose levels during an oral glucose tolerance test
      (OGTT) may be useful for predicting diabetes or cardiovascular disease (CVD). Our
      aim was to determine whether the time to peak glucose during the OGTT is
      associated with CVD risk scores and diabetes. METHODS: Individuals with impaired
      fasting glucose (IFG) were enrolled in this observational study. Participants
      were grouped by the measured time to peak glucose (30, 60, 90 and 120 min) during
      the 75g OGTT. The primary outcome was 10-year CVD risk scores (using the
      Framingham risk score calculator). Secondary outcomes evaluated effect of time to
      peak glucose on prevalence of diabetes and indicators of glucose homeostasis.
      RESULTS: A total of 125 patients with IFG underwent OGTTs. Framingham 10-year
      risk score for the 90-min group was 1.7 times higher than for the 60-min group
      (6.98+/-6.56% vs. 4.05+/-4.60%, P = 0.023). Based on multivariate linear
      regression, time to peak glucose at 90 min was associated with a higher
      Framingham risk score than 60-min group (beta coefficient: 2.043, 95% confidence
      interval: 0.067-6.008, P = 0.045). The percentages of patients with HbA1c >=6.5%,
      isolated post-challenge hyperglycemia (IPH) and diabetes (combined IPH and HbA1c
      >=6.5%) were significantly increased with longer times to peak glucose.
      Prevalence of diabetes was higher in the 90-min group than in the 60-min group
      (31.5% vs. 5.7%, P = 0.001). CONCLUSIONS: In subjects with IFG, those with a
      longer time to peak glucose had a higher Framingham 10-year risk score and were
      associated with a greater likelihood of IPH and diabetes.

PMID- 29216250
TI  - A randomized controlled trial of Roux-en-Y gastrojejunostomy vs.
      gastroduodenostomy with respect to the improvement of type 2 diabetes mellitus
      after distal gastrectomy in gastric cancer patients.
AB  - The purpose of this study is to compare the effect of diabetes control induced by
      Roux-en-Y gastrojejunostomy(RY) vs Billroth-I reconstruction(BI) after distal
      gastrectomy in patients with early gastric cancer(EGC) and type 2 diabetes(T2DM).
      Forty EGC patients with T2DM, aged 20-80 years, who were expected to undergo
      curative distal gastrectomy were randomized 1:1 to RY(n = 20) or BI(n = 20).
      Diabetes medication status, biochemical and hormonal data including blood
      glucose, HbA1c, insulin, C-peptide, HOMA-IR, ghrelin, leptin, GLP-1, PYY, and GIP
      were evaluated for 12 months after surgery. Although pre- and postoperative 12
      month fasting and postprandial glucose levels did not show a significant
      difference, HbA1c, C-peptide, and HOMA-IR levels were significantly improved at
      12 months after surgery in both BI and RY groups. Sixty percent of RY patients
      and 20% of BI patients decreased their medication satisfying FBS<126 mg/dL and
      HbA1c<6.5% and 5% of BI patients stopped their medication satisfying the criteria
      of FBS<126 mg/dL and HbA1c<6.0%. The improvement patterns were more sustainable
      with less fluctuation in RY than in BI. On hormonal analysis, ghrelin and leptin
      levels were decreased and PYY and GIP levels were increased at 12 months after
      surgery in both groups without significant difference according to the
      reconstruction type and diabetic improvement status except ghrelin. In gastric
      cancer surgery, RY reconstruction showed better and more durable diabetes control
      compared to BI during the first year after surgery. Gastric cancer surgery led to
      decreased ghrelin and leptin and increased PYY and GIP, which might have a role
      in improving insulin resistance and glucose homeostasis.

PMID- 29216251
TI  - Molecular characterization of hepatitis B virus in Bangladesh reveals a highly
      recombinant population.
AB  - The natural history and treatment outcome of hepatitis B viruses (HBV) infection
      is largely dependent on genotype, subgenotype, and the presence or absence of
      virulence associated mutations. We have studied the prevalence of genotype and
      subgenotype as well as virulence and drug resistance associated mutations and
      prevalence of recombinant among HBV from Bangladesh. A prospective cross
      sectional study was conducted among treatment naive chronic HBV patients
      attending at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh for
      HBV viral load assessment between June and August 2015. Systematical selected 50%
      of HBV DNA positive patients (every second patient) were enrolled. Biochemical
      and serological markers for HBV infection and whole genome sequencing (WGS) was
      performed on virus positive sample. Genotype, subgenotype, virulence,
      nucleos(t)ide analogue (NA) resistance (NAr) mutations, and the prevalence of
      recombinant isolates were determined. Among 114 HBV DNA positive patients, 57
      were enrolled in the study and 53 HBV WGS were generated for downstream analysis.
      Overall, 38% (22/57) and 62% (35/57) of patients had acute and chronic HBV
      infections, respectively. The prevalence of genotypes A, C, and D was 18.9%
      (10/53), 45.3% (24/53), and 35.8% (19/53), respectively. Among genotype A, C and
      D isolates subgenotype A1 (90%; 9/10), C1 (87.5%; 21/24) and D2 (78.9%; 15/19)
      predominates. The acute infection, virulence associated mutations, and viral load
      was higher in the genotype D isolates. Evidence of recombination was identified
      in 22.6% (12/53) of the HBV isolates including 20.0% (2/10), and 16.7% (4/24) and
      31.6% (6/19) of genotype A, C and D isolates, respectively. The prevalence of
      recombination was higher in chronic HVB patients (32.2%; 10/31 versus 9.1%;
      2/22); p<0.05. NAr mutations were identified in 47.2% (25/53) of the isolates
      including 33.9% novel mutations (18/53). HBV genotype C and D predominated in
      this population in Bangladesh; a comparatively high prevalence of recombinant HBV
      are circulating in this setting.

PMID- 29216252
TI  - Global computational mutagenesis provides a critical stability framework in
      protein structures.
AB  - A protein's amino acid sequence dictates the folds and final structure the
      macromolecule will form. We propose that by identifying critical residues in a
      protein's atomic structure, we can select a critical stability framework within
      the protein structure essential to proper protein folding. We use global
      computational mutagenesis based on the unfolding mutation screen to test the
      effect of every possible missense mutation on the protein structure to identify
      the residues that cannot tolerate a substitution without causing protein
      misfolding. This method was tested using molecular dynamics to simulate the
      stability effects of mutating critical residues in proteins involved in inherited
      disease, such as myoglobin, p53, and the 15th sushi domain of complement factor
      H. In addition we prove that when the critical residues are in place, other
      residues may be changed within the structure without a stability loss. We
      validate that critical residues are conserved using myoglobin to show that
      critical residues are the same for crystal structures of 6 different species and
      comparing conservation indices to critical residues in 9 eye disease-related
      proteins. Our studies demonstrate that by using a selection of critical elements
      in a protein structure we can identify a critical protein stability framework.
      The frame of critical residues can be used in genetic engineering to improve
      small molecule binding for drug studies, identify loss-of-function disease
      causing missense mutations in genetics studies, and aide in identifying templates
      for homology modeling.

PMID- 29216253
TI  - Changes in social capital and depressive states of middle-aged adults in Japan.
AB  - The present study examines the relationships between changes in bonding and
      bridging types of social capital and depressive states among middle-aged adults
      in Japan using a nationally representative sample. Data was collected from a
      nationwide, population-based survey conducted from 2005 to 2013 in nine annual
      waves. A total of 16,737 middle-aged men and 17,768 middle-aged women provided
      data. They reported about depressive states, measured by Kessler 6 scores, and
      bonding and bridging types of social capital, measured by reported participation
      in different social activities. Latent growth modeling was conducted to examine
      relations between changes in bonding and bridging types of social capital and
      depressive states within individuals across the nine waves. The results showed
      that, for both men and women, increases in bonding social capital were associated
      with decreases in depressive states, while changes in bridging social capital
      were not related to changes in depressive states. In addition, the results showed
      that changes in bonding social capital, but not bonding social capital at the
      baseline, affected changes in depressive states. Future studies should take
      changes in social capital as an independent variable into consideration.

PMID- 29216255
TI  - Forecasting success via early adoptions analysis: A data-driven study.
AB  - Innovations are continuously launched over markets, such as new products over the
      retail market or new artists over the music scene. Some innovations become a
      success; others don't. Forecasting which innovations will succeed at the
      beginning of their lifecycle is hard. In this paper, we provide a data-driven,
      large-scale account of the existence of a special niche among early adopters,
      individuals that consistently tend to adopt successful innovations before they
      reach success: we will call them Hit-Savvy. Hit-Savvy can be discovered in very
      different markets and retain over time their ability to anticipate the success of
      innovations. As our second contribution, we devise a predictive analytical
      process, exploiting Hit-Savvy as signals, which achieves high accuracy in the
      early-stage prediction of successful innovations, far beyond the reach of state
      of-the-art time series forecasting models. Indeed, our findings and predictive
      model can be fruitfully used to support marketing strategies and product
      placement.

PMID- 29216254
TI  - International Classification of Diseases (ICD)-coded obesity predicts risk of
      incident osteoporotic fracture.
AB  - International Classification of Diseases (ICD) codes have been used to ascertain
      individuals who are obese. There has been limited research about the predictive
      value of ICD-coded obesity for major chronic conditions at the population level.
      We tested the utility of ICD-coded obesity versus measured obesity for predicting
      incident major osteoporotic fracture (MOF), after adjusting for covariates (i.e.,
      age and sex). In this historical cohort study (2001-2015), we selected 61,854
      individuals aged 50 years and older from the Manitoba Bone Mineral Density
      Database, Canada. Body mass index (BMI) >=30 kg/m2 was used to define measured
      obesity. Hospital and physician ICD codes were used to ascertain ICD-coded
      obesity and incident MOF. Average cohort age was 66.3 years and 90.3% were
      female. The sensitivity, specificity and positive predictive value for ICD-coded
      obesity using measured obesity as the reference were 0.11 (95% confidence
      interval [CI]: 0.10, 0.11), 0.99 (95% CI: 0.99, 0.99) and 0.79 (95% CI: 0.77,
      0.81), respectively. ICD-coded obesity (adjusted hazard ratio [HR] 0.83; 95% CI:
      0.70, 0.99) and measured obesity (adjusted HR 0.83; 95% CI: 0.78, 0.88) were
      associated with decreased MOF risk. Although the area under the receiver
      operating characteristic curve (AUROC) estimates for incident MOF were not
      significantly different for ICD-coded obesity versus measured obesity (0.648 for
      ICD-coded obesity versus 0.650 for measured obesity; P = 0.056 for AUROC
      difference), the category-free net reclassification index for ICD-coded obesity
      versus measured obesity was -0.08 (95% CI: -0.11, -0.06) for predicting incident
      MOF. ICD-coded obesity predicted incident MOF, though it had low sensitivity and
      reclassified MOF risk slightly less well than measured obesity.

PMID- 29216257
TI  - A decoy chain deployment method based on SDN and NFV against penetration attack.
AB  - Penetration attacks are one of the most serious network security threats.
      However, existing network defense technologies do not have the ability to
      entirely block the penetration behavior of intruders. Therefore, the network
      needs additional defenses. In this paper, a decoy chain deployment (DCD) method
      based on SDN+NFV is proposed to address this problem. This method considers about
      the security status of networks, and deploys decoy chains with the resource
      constraints. DCD changes the attack surface of the network and makes it difficult
      for intruders to discern the current state of the network. Simulation experiments
      and analyses show that DCD can effectively resist penetration attacks by
      increasing the time cost and complexity of a penetration attack.

PMID- 29216256
TI  - DNA methylation levels in candidate genes associated with chronological age in
      mammals are not conserved in a long-lived seabird.
AB  - Most seabirds do not have any outward identifiers of their chronological age, so
      estimation of seabird population age structure generally requires expensive, long
      term banding studies. We investigated the potential to use a molecular age
      biomarker to estimate age in short-tailed shearwaters (Ardenna tenuirostris). We
      quantified DNA methylation in several A. tenuirostris genes that have shown age
      related methylation changes in mammals. In birds ranging from chicks to 21 years
      of age, bisulphite treated blood and feather DNA was sequenced and methylation
      levels analysed in 67 CpG sites in 13 target gene regions. From blood samples,
      five of the top relationships with age were identified in KCNC3 loci (CpG66: R2 =
      0.325, p = 0.019). In feather samples ELOVL2 (CpG42: R2 = 0.285, p = 0.00048) and
      EDARADD (CpG46: R2 = 0.168, p = 0.0067) were also weakly correlated with age.
      However, the majority of markers had no clear association with age (of 131
      comparisons only 12 had a p-value < 0.05) and statistical analysis using a
      penalised lasso approach did not produce an accurate ageing model. Our data
      indicate that some age-related signatures identified in orthologous mammalian
      genes are not conserved in the long-lived short tailed shearwater. Alternative
      molecular approaches will be required to identify a reliable biomarker of
      chronological age in these seabirds.

PMID- 29216258
TI  - Drought stress leads to systemic induced susceptibility to a nectrotrophic fungus
      associated with mountain pine beetle in Pinus banksiana seedlings.
AB  - Conifers have complex defense responses to initial attacks by insects and
      pathogens that can have cascading effects on success of subsequent colonizers.
      However, drought can affect a plant's ability to respond to biotic agents by
      potentially altering the resources needed for the energetically costly production
      of induced defense chemicals. We investigated the impact of reduced water on
      induced chemical defenses of jack pine (Pinus banksiana) seedlings from initial
      attack by biotic agents and resistance to subsequent challenge inoculation with a
      pathogenic fungal associate of mountain pine beetle (Dendroctonus ponderosae),
      Grosmannia clavigera. Applications of phytohormones (methyl salicylate and methyl
      jasmonate) and G. clavigera were used for initial induction of defenses.
      Monoterpene concentrations varied with initial induction from fungal and
      phytohormone application while watering treatment had no effect. Seedlings
      treated with G. clavigera and methyl jasmonate had the greatest monoterpene
      concentrations compared to the control and methyl salicylate-treated seedlings.
      However, the monoterpene response to the challenge inoculation varied with
      watering treatments, not with prior induction treatments, with lower monoterpene
      concentrations in fungal lesions on seedlings in the low to moderate watering
      treatments compared to normal watering treatment. Furthermore, prior induction
      from phytohormones resulted in systemic cross-induction of resistance to G.
      clavigera under normal watering treatment but susceptibility under low watering
      treatment. Seedlings stressed by low water conditions, which also had lower
      stomatal conductance than seedlings in the normal watering treatment, likely
      allocated resources to initial defense response but were left unable to acquire
      further resources for subsequent responses. Our results demonstrate that drought
      can affect interactions among tree-infesting organisms through systemic cross
      induction of susceptibility.

PMID- 29216259
TI  - The prognostic impact of the platelet distribution width-to-platelet count ratio
      in patients with breast cancer.
AB  - Activated platelets promote tumor cell growth, angiogenesis, and invasion.
      Platelet activity can be inferred by platelet volume indices (PVIs), which
      include platelet distribution width (PDW), mean platelet volume (MPV), platelet
      distribution width-to-platelet count ratio (PDW/P), and mean platelet volume-to
      platelet count ratio. Platelets and platelet-related markers, such as the
      platelet-to-lymphocyte ratio, have been found to be significant prognostic
      factors in patients with breast cancer. However, the role of PVIs for predicting
      survival in breast cancer remains unknown; hence, we performed this retrospective
      analysis of 275 patients with breast cancer. PVIs were compared with
      clinicopathological variables, and were assessed to identify independent
      indicators associated with disease-free survival (DFS) using the Cox proportional
      hazards model. An elevated PDW/P significantly correlated with age and HER2
      status. Univariate analysis revealed that elevated PDW, MPV, and PDW/P as well as
      tumor size, nuclear grade, and lymph node involvement were significantly
      associated with inferior DFS rates (tumor size: p<0.01; nuclear grade, lymph node
      involvement, PDW, MPV, and PDW/P: p<0.05). On multivariate analysis, a large
      tumor size and elevated PDW/P were significant prognostic factors for DFS, with
      hazard ratios of 3.24 (95% confidence interval [CI]: 1.24-8.47) and 2.99 (95% CI:
      1.18-7.57), respectively (p<0.05). Our study is the first to reveal that an
      elevated PDW/P significantly reduces DFS in patients with breast carcinoma.
      Measuring the PDW/P is simple, relatively inexpensive, and almost universally
      available using routine blood counts; this makes it an attractive biomarker for
      improved risk assessment.

PMID- 29216260
TI  - Angiotensin receptor blockers are associated with lower mortality than ACE
      inhibitors in predialytic stage 5 chronic kidney disease: A nationwide study of
      therapy with renin-angiotensin system blockade.
AB  - Dual renin angiotensin system (RAS) blockade using angiotensin-receptor blockers
      (ARBs) in combination with angiotensin converting enzyme inhibitors (ACEIs) is
      reported to improve proteinuria in both diabetic and non-diabetic patients.
      However, its renoprotective effect and safety remain uncertain in patients with
      advanced chronic kidney disease (CKD). From January 1, 2000 through June 30,
      2009, we enrolled 14,117 pre-dialytic stage 5 CKD patients with serum creatinine
      >6mg/dL and hematocrit <28% under the treatment with erythropoiesis stimulating
      agents and RAS blockade. We used Cox proportional hazards regression models to
      estimate the hazard ratios (HRs) against the commencement of long-term dialysis
      and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months,
      9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before
      progression to end-stage renal disease requiring dialysis. In comparison with the
      ARB-only users, dual blockade with ACEIs and ARBs was associated with a
      significantly higher risk of (1) death in all CKD patients (HR = 1.49, [95%CI,
      1.30-1.71]; P = 0.02) and in diabetic subgroup (HR = 1.58, [95%CI, 1.34-1.86]; P
      = 0.02); (2) composite endpoint of long-term dialysis or death in diabetic
      subgroup (HR = 1.10, [95%CI, 1.01-1.20]; P = 0.04); (3) hyperkalemia-associated
      hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05-7.15]; P =
      0.04). However, ACEIs users were associated with higher mortality than ARBs users
      in all CKD patients (HR = 1.17, [95%CI, 1.07-1.27]; P = 0.03) and in diabetic
      subgroup (HR = 1.32, [95%CI, 1.18-1.48]; P = 0.03). Monotherapy of RAS blockade,
      especially ARB, is more effective and safer than dual RAS blockade in pre
      dialytic stage 5 CKD patients.

PMID- 29216261
TI  - Associations of changes in body mass index with all-cause and cardiovascular
      mortality in healthy middle-aged adults.
AB  - BACKGROUND: Conflicting data exist regarding the association of body mass index
      (BMI) changes with all-cause and cardiovascular (CV) mortality. The current study
      investigated the association between changes in BMI and all-cause, CV, and non-CV
      mortality in a large cohort of middle-aged adults. METHODS: A total of 379,535
      adults over 40 years of age without pre-existing CV disease or cancer at baseline
      were enrolled to undergo a series of at least three health examinations of
      biennial intervals. Changes in BMI between baseline, midpoint follow-up, and
      final health examination during mean 9.3 years were defined according to the
      pattern of BMI change as follows: stable, sustained gain, sustained loss, and
      fluctuation. The relationship between BMI change category and mortality was
      assessed by multivariate Cox regression reporting hazard ratio (HR) with 95%
      confidence interval (95% CI). RESULTS: During a mean follow-up of 10.7 years for
      mortality, 12,378 deaths occurred from all causes, of which 2,114 were CV and
      10,264 were non-CV deaths. Sustained BMI gain was associated with the lower risk
      of all-cause (HR 0.89, 95% CI: 0.83-0.95), CV (HR 0.84, 95% CI 0.72-0.98), and
      non-CV mortality (HR 0.90, 95% CI 0.84-0.96) compared with stable BMI.
      Conversely, sustained BMI loss (HR 1.25, 95% CI 1.19-1.32) and fluctuation (HR
      1.13, 95% CI 1.08-1.19) displayed a higher risk of all-cause mortality compared
      with stable BMI, which was mainly attributable to the increase in non-CV
      mortality. CONCLUSION: Sustained BMI gains were associated with reduced risk of
      all-cause, CV, and non-CV mortality in middle-aged healthy adults.

PMID- 29216262
TI  - Direct detection of Mycobacterium tuberculosis rifampin resistance in bio-safe
      stained sputum smears.
AB  - Direct smear microscopy of sputum forms the mainstay of TB diagnosis in resource
      limited settings. Stained sputum smear slides can serve as a ready-made resource
      to transport sputum for molecular drug susceptibility testing. However, bio
      safety is a major concern during transport of sputum/stained slides and for
      laboratory workers engaged in processing Mycobacterium tuberculosis infected
      sputum specimens. In this study, a bio-safe USP (Universal Sample Processing)
      concentration-based sputum processing method (Bio-safe method) was assessed on 87
      M. tuberculosis culture positive sputum samples. Samples were processed for Ziehl
      Neelsen (ZN) smear, liquid culture and DNA isolation. DNA isolated directly from
      sputum was subjected to an IS6110 PCR assay. Both sputum DNA and DNA extracted
      from bio-safe ZN concentrated smear slides were subjected to rpoB PCR and
      simultaneously assessed by DNA sequencing for determining rifampin (RIF)
      resistance. All sputum samples were rendered sterile by Bio-safe method. Bio-safe
      smears exhibited a 5% increment in positivity over direct smear with a 14%
      increment in smear grade status. All samples were positive for IS6110 and rpoB
      PCR. Thirty four percent samples were RIF resistant by rpoB PCR product
      sequencing. A 100% concordance (kappa value = 1) was obtained between sequencing
      results derived from bio-safe smear slides and bio-safe sputum. This study
      demonstrates that Bio-safe method can address safety issues associated with
      sputum processing, provide an efficient alternative to sample transport in the
      form of bio-safe stained concentrated smear slides and can also provide
      information on drug (RIF) resistance by direct DNA sequencing.

PMID- 29216263
TI  - Roles, responsibilities and characteristics of lay community health workers
      involved in diabetes prevention programmes: A systematic review.
AB  - AIM: To examine the characteristics of community health workers (CHWs) involved
      in diabetes prevention programmes (DPPs) and their contributions to expected
      outcomes. METHODS: Electronic databases including PubMed-MEDLINE, EBSCOHost, and
      SCOPUS/EMBASE were searched for studies published between January 2000 and March
      2016. All studies that used CHWs to implement DPP in >=18-year-old participants
      without diabetes but at high risk for developing the condition, irrespective of
      the study design, setting or outcomes measured, were included. Results were
      synthesized narratively. RESULTS: Forty papers of 30 studies were identified.
      Studies were mainly community-based and conducted in minority populations in USA.
      Sample sizes ranged from 20 participants in a single community to 2369
      participants in 46 communities. Although CHWs were generally from the local
      community, their qualifications, work experience and training received differed
      across studies. Overall the training was culturally sensitive and/or appropriate,
      covering topics such as the importance of good nutrition and the benefits of
      increased physical activity, communication and leadership. CHWs delivered a
      variety of interventions and also screened or recruited participants. The shared
      culture and language between CHWs and participants likely contributed to better
      programme implementation and successful outcomes. CONCLUSIONS: The complexity of
      DPPs and the diverse CHW roles preclude attributing specific outcomes to CHW
      involvement. Nevertheless, documenting potential CHW roles and the relevant
      training required may optimise CHW contributions and facilitate their involvement
      in DPPs in the future.

PMID- 29216264
TI  - A pressure-based force and torque prediction technique for the study of fish-like
      swimming.
AB  - Many outstanding questions about the evolution and function of fish morphology
      are linked to swimming dynamics, and a detailed knowledge of time-varying forces
      and torques along the animal's body is a key component in answering many of these
      questions. Yet, quantifying these forces and torques experimentally represents a
      major challenge that to date prevents a full understanding of fish-like swimming.
      Here, we develop a method for obtaining these force and torque data non
      invasively using standard 2D digital particle image velocimetry in conjunction
      with a pressure field algorithm. We use a mechanical flapping foil apparatus to
      model fish-like swimming and measure forces and torques directly with a load
      cell, and compare these measured values to those estimated simultaneously using
      our pressure-based approach. We demonstrate that, when out-of-plane flows are
      relatively small compared to the planar flow, and when pressure effects
      sufficiently dominate shear effects, this technique is able to accurately
      reproduce the shape, magnitude, and timing of locomotor forces and torques
      experienced by a fish-like swimmer. We conclude by exploring of the limits of
      this approach and its feasibility in the study of freely-swimming fishes.

PMID- 29216266
TI  - Identification and genetic characterization of hepacivirus and pegivirus in
      commercial equine serum products in China.
AB  - Equine hepacivirus (EqHV), equine pegivirus (EPgV) and Theiler's disease
      associated virus (TDAV) are three novel equine viruses in the family
      Flaviviridae. EqHV and EPgV have been identified to circulate in the equine
      population worldwide, whereas TDAV has not been detected in equines since the
      first reported case. To date, no studies have focused on investigating EqHV, EPgV
      and TDAV in commercial equine sera or equine blood products in China. Considering
      the potential threat of EqHV, EPgV and TDAV to biosecurity and considering their
      possible influences on research results, equine sera for cell culture propagation
      and pregnant mare serum gonadotropin (PMSG) were purchased from different
      companies in China and investigated for EqHV, EPgV and TDAV in this study. By
      performing nested PCR or two rounds of PCR targeting the viral NS3 gene, four
      serum samples were confirmed to be EqHV-, EPgV-, or TDAV-RNA positive; all of the
      PMSG samples were negative for these three viruses. Subsequent sequencing results
      indicated that the serum samples contained multiple viral variants of EqHV, EPgV
      or TDAV, and a genetic analysis based on the partial NS3 gene of the three equine
      viruses was performed. Our study is the first to confirm the presence of EqHV,
      EPgV and TDAV in equine sera for cell culture propagation that is commercially
      available in China and provides the first demonstration of the presence of TDAV
      in China.

PMID- 29216265
TI  - OCT4 expression mediates partial cardiomyocyte reprogramming of mesenchymal
      stromal cells.
AB  - Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical
      trials, including for injured myocardium. Acquisition of cardiomyocyte
      characteristics by MSCs may improve cardiac regeneration but the mechanisms
      regulating this process are unclear. Here, we investigated whether the
      pluripotency transcription factor OCT4 is involved in the activation of cardiac
      lineage genetic programs in MSCs. We employed our established co-culture model of
      MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers
      on MSCs independent of cell fusion. Bone marrow-derived MSCs were isolated from
      transgenic mice expressing GFP under the control of the cardiac-specific alpha
      myosin heavy chain promoter. After 5 days of co-culture, MSCs expressed cardiac
      specific genes, including Nkx2.5, atrial natriuretic factor and alpha-cardiac
      actin. The frequency of GFP+ cells was 7.6+/-1.9%, however, these cells retained
      the stromal cell phenotype, indicating, as expected, only partial
      differentiation. Global OCT4 expression increased 2.6+/-0.7-fold in co-cultured
      MSCs and of interest, 87+/-5% vs 79+/-4% of MSCs expressed OCT4 by flow cytometry
      in controls and after co-culture, respectively. Consistent with the latter
      observation, the GFP+ cells did not express nuclear OCT4 and showed a significant
      increase in OCT4 promoter methylation compared with undifferentiated MSCs (92% vs
      45%), inferring that OCT4 is regulated by an epigenetic mechanism. We further
      showed that siRNA silencing of OCT4 in MSCs resulted in a reduced frequency of
      GFP+ cells in co-culture to less than 1%. Our data infer that OCT4 expression may
      have a direct effect on partial cardiomyocyte reprogramming of MSCs and suggest a
      new mechanism(s) associated with MSC multipotency and a requirement for crosstalk
      with the cardiac microenvironment.

PMID- 29216267
TI  - Altered postural sway following fatiguing foot muscle exercises.
AB  - This study investigated the acute effects of fatiguing foot muscle exercises on
      the maximum muscle strength of the foot and postural control ability. Eighteen
      healthy young individuals performed fatiguing foot muscle strength exercises, and
      their toe flexor and ankle plantar flexor strength and postural control ability
      were measured before and after the exercises. Postural control ability was
      evaluated using the path of the center of pressure (COP) during three balance
      tasks: double-leg standing with eyes open; double-leg standing with eyes closed;
      and single-leg standing with eyes open. After the exercises, the muscle strength
      of both the toe and ankle plantar flexor significantly decreased. Under all of
      the conditions, most COP variables did not significantly differ before and after
      the exercises; however, the total length and mean velocity in the single-leg
      standing with eyes open significantly decreased after the exercises. Postural
      sway velocities in the anteroposterior direction of double-leg standing with eyes
      closed and in both anteroposterior and mediolateral directions of single-leg
      standing with eyes open significantly decreased after the exercises. The
      associations between relative changes in muscle strength after the exercise and
      relative changes in COP variables after the exercise were not found. These
      results indicate that postural control while standing could be maintained even
      though foot muscle strength is decreased after fatiguing foot muscle exercises.

PMID- 29216268
TI  - Docking and quantitative structure-activity relationship of bi-cyclic
      heteroaromatic pyridazinone and pyrazolone derivatives as phosphodiesterase 3A
      (PDE3A) inhibitors.
AB  - PDE3s belong to the phosphodiesterases family, where the PDE3A isoform is the
      major subtype in platelets involved in the cAMP regulation pathway of platelet
      aggregation. PDE3A inhibitors have been designed as potential antiplatelet
      agents. In this work, a homology model of PDE3A was developed and used to obtain
      the binding modes of bicyclic heteroaromatic pyridazinones and pyrazolones. Most
      of the studied compounds adopted similar orientations within the PDE3A active
      site, establishing hydrogen bonds with catalytic amino acids. Besides, the
      structure-activity relationship of the studied inhibitors was described by using
      a field-based 3D-QSAR method. Different structure alignment strategies were
      employed, including template-based and docking-based alignments. Adequate
      correlation models were obtained according to internal and external validations.
      In general, QSAR models revealed that steric and hydrophobic fields describe the
      different inhibitory activities of the compounds, where the hydrogen bond donor
      and acceptor fields have minor contributions. It should be stressed that
      structural elements of PDE3A inhibitors are reported here, through descriptions
      of their binding interactions and their differential affinities. In this sense,
      the present results could be useful in the future design of more specific and
      potent PDE3A inhibitors that may be used for the treatment of cardiovascular
      diseases.

PMID- 29216269
TI  - Compensatory role of Neuroglobin in nervous and non-nervous cancer cells in
      response to the nutrient deprivation.
AB  - Environmental factors or adverse growth conditions that may reduce cell function
      or viability are considered stress. The cell ability to sense and respond to
      environmental stresses determine its function and survival destiny. We recently
      defined Neuroglobin (NGB), a heme-protein, as a compensatory protein in the
      17beta-Estradiol (E2) anti-apoptotic activity and as a sensor of oxidative stress
      in both neurons and breast cancer cells. Here, the possibility that NGB levels
      could represent a pivotal regulator of integrated response of cancer cells to
      stress has been evaluated. Data obtained in neuroblastoma and in breast cancer
      cell lines evidence that nutrient deprivation significantly up-regulated NGB
      levels at different time points. However, the analysis of autophagy activation
      led to exclude any possible role of stress- or E2-induced NGB in the upstream
      regulation of general autophagy. However, the over-expression of Flag-NGB in
      ERalpha stable transfected HEK-293 cells completely affects nutrient deprivation
      induced decrease in cell number. In addition, reported results indicate that
      modulation of the anti-apoptotic Bcl-2 level may play a key role in the
      protective NGB function against energetic stress. Overall, these data define a
      role of NGB as compensatory protein in the cell machinery activated in response
      to stress and as general stress adaptation marker of cancer cells susceptible to
      oxidative stress, oxygen and, as demonstrated here for the first time, even to
      nutrient willingness. Despite the lacking of any direct NGB role on autophagic
      flux activated by energetic stress, NGB upregulation appears functional in
      delaying stress-related cell death allowing an appropriate cell response and
      adaptation to the changing extracellular conditions.

PMID- 29216270
TI  - Generation and characterization of Kctd15 mutations in zebrafish.
AB  - Potassium channel tetramerization domain containing 15 (Kctd15) was previously
      found to have a role in early neural crest (NC) patterning, specifically
      delimiting the region where NC markers are expressed via repression of
      transcription factor AP-2a and inhibition of Wnt signaling. We used transcription
      activator-like effector nucleases (TALENs) to generate null mutations in
      zebrafish kctd15a and kctd15b paralogs to study the in vivo role of Kctd15. We
      found that while deletions producing frame-shift mutations in each paralog showed
      no apparent phenotype, kctd15a/b double mutant zebrafish are smaller in size and
      show several phenotypes including some affecting the NC, such as expansion of the
      early NC domain, increased pigmentation, and craniofacial defects. Both
      melanophore and xanthophore pigment cell numbers and early markers are up
      regulated in the double mutants. While we find no embryonic craniofacial defects,
      adult mutants have a deformed maxillary segment and missing barbels. By confocal
      imaging of mutant larval brains we found that the torus lateralis (TLa), a region
      implicated in gustatory networks in other fish, is absent. Ablation of this brain
      tissue in wild type larvae mimics some aspects of the mutant growth phenotype.
      Thus kctd15 mutants show deficits in the development of both neural crest
      derivatives, and specific regions within the central nervous system, leading to a
      strong reduction in normal growth rates.

PMID- 29216271
TI  - Genomic and phenotypic characteristics of Swedish C. jejuni water isolates.
AB  - Campylobacter jejuni is the most common cause of bacterial gastroenteritis. Major
      reservoirs are warm-blooded animals, poultry in particular, but Campylobacter can
      also be transmitted via water. In this paper, we have taken a closer look at the
      biology and potential virulence of C. jejuni water isolates. Seven C. jejuni
      isolates from incoming surface water at water plants in Sweden were characterized
      with whole genome sequencing and phenotypical testing. Multi locus sequence
      typing analysis revealed that these isolates belonged to groups known to include
      both common (ST48CC) and uncommon (ST1275CC, ST683, ST793 and ST8853) human
      pathogens. Further genomic characterization revealed that these isolates had
      potential for arsenic resistance (due to presence of arsB gene in all isolates),
      an anaerobic dimethyl sulfoxide oxidoreductase (in three isolates) and lacked the
      MarR-type transcriptional regulator gene rrpB (in all but one isolate) earlier
      shown to be involved in better survival under oxidative and aerobic stress. As
      putative virulence factors were concerned, there were differences between the
      water isolates in the presence of genes coding for cytolethal distending toxin
      (cdtABC), Type VI secretion system and sialylated LOS, as well as in biofilm
      formation. However, all isolates were motile and could adhere to and invade the
      human HT-29 colon cancer cell line in vitro and induce IL-8 secretion suggesting
      potential to infect humans. This is, to the best of our knowledge, the first
      study where C. jejuni water isolates have been characterized using whole genome
      sequencing and phenotypical assays. We found differences and shared traits among
      the isolates but also potential to infect humans.

PMID- 29216272
TI  - A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b.
AB  - Different test systems are used to characterize the anti-aggregation efficiency
      of molecular chaperone proteins and of low-molecular-weight chemical chaperones.
      Test systems based on aggregation of UV-irradiated protein are of special
      interest because they allow studying the protective action of different agents at
      physiological temperatures. The kinetics of UV-irradiated glycogen phosphorylase
      b (UV-Phb) from rabbit skeletal muscle was studied at 37 degrees C using dynamic
      light scattering in a wide range of protein concentrations. It has been shown
      that the order of aggregation with respect to the protein is equal to unity. A
      conclusion has been made that the rate-limiting stage of the overall process of
      aggregation is heat-induced structural reorganization of a UV-Phb molecule, which
      contains concealed damage.

PMID- 29216273
TI  - Isoniazid concentrations in hair and plasma area-under-the-curve exposure among
      children with tuberculosis.
AB  - We measured hair and plasma concentrations of isoniazid among sixteen children
      with tuberculosis who underwent personal or video-assisted directly observed
      therapy and thus had 100% adherence. This study therefore defined typical
      isoniazid exposure parameters after two months of treatment among fully-adherent
      patients in both hair and plasma (plasma area under the concentration-time curve,
      AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after
      drug administration). We found that INH levels in hair among highly-adherent
      individuals did not correlate well with plasma AUC or trough concentrations,
      suggesting that each measure may provide incremental and complementary
      information regarding drug exposure in the context of TB treatment.

PMID- 29216274
TI  - Functional analysis of a CDKN2A 5'UTR germline variant associated with pancreatic
      cancer development.
AB  - CDKN2A coding region germline variants are associated with pancreatic
      adenocarcinoma (PC) susceptibility. Recently, we described functional germline
      5'UTR CDKN2A variants from melanoma patients affecting the post-transcriptional
      regulation of p16INK4a mRNA that is dependent, at least in part, on an Internal
      Ribosome Entry Site (IRES) in the 5'UTR region. Here we describe a 5'UTR c.-201_
      198delinsCTTT CDKN2A variant (frequency 0.0028 based on 350 PC patients), which
      seems to be private to PC, since it has never been found in public databases nor
      in thousands of melanoma patients tested. Functional analyses confirmed IRES
      activity of the 5'UTR in BX-PC3 PC cells and revealed a functional impact of the
      identified variant. Using gene reporter assays we observed reduced translation
      potential in cells treated with the mTOR inhibitor Torin1, a condition that
      favors the assessment of IRES activity. At the endogenous gene level we
      quantified allelic imbalance among polysome-associated mRNAs using a patient
      derived cell line heterozygous for the c.-201_-198delinsCTTT. Overall, we
      conclude that this very rare private variant can be considered a potential
      mutation, specifically associated with PC. Our data indicate that sequencing of
      the entire 5'UTR of CDKN2A should be included in routine screening of PC cases
      with suspected inherited susceptibility.

PMID- 29216275
TI  - Co-existence of multiple trade-off currencies shapes evolutionary outcomes.
AB  - Evolutionary studies often assume that energy is the primary resource (i.e.
      "currency") at the heart of the survival-reproduction trade-off, despite recent
      evidence to the contrary. The evolutionary consequences of having a single trade
      off currency versus multiple competing currencies are unknown. Using simulations,
      we modeled the evolution of either a single physiological currency between
      reproduction and survival, or of multiple such currencies. For a wide array of
      model specifications varying functional forms and strengths of the trade-offs, we
      show that the presence of multiple currencies (e.g. nutrients, time) generally
      results in the evolution of higher lifetime reproductive success through partial
      circumvention of such trade-offs. Evolution of the underlying physiology is also
      more highly contingent with multiple currencies. These results challenge the
      paradigm of a single survival-reproduction trade-off as central to life history
      evolution, suggesting greater roles for physiological constraints and
      contingency, and implying potential selection for evolution of multiple trade-off
      currencies.

PMID- 29216276
TI  - National epidemiology of initial and recurrent Clostridium difficile infection in
      the Veterans Health Administration from 2003 to 2014.
AB  - INTRODUCTION: Prior studies demonstrated marked increases in Clostridium
      difficile infection (CDI) in the United States (U.S.) in recent years. The
      objective of this study was to describe the epidemiology of initial and recurrent
      CDI in a national Veterans Health Administration (VHA) cohort over a 12-year
      period. METHODS: This was a retrospective cohort study of all adult VHA
      beneficiaries with CDI (ICD-9-CM code 008.45) plus a positive CDI stool test
      between October 1, 2002 and September 30, 2014. Data were obtained from the VA
      Informatics and Computing Infrastructure. Recurrence was defined as a second ICD
      9-CM code plus a new course of CDI therapy following a minimum three-day gap
      after the initial therapy was completed. CDI incidence and outcomes were
      presented descriptively and longitudinally. RESULTS: Overall, 30,326 patients met
      study inclusion criteria. CDI incidence increased from FY 2003 (1.6 per 10,000)
      to FY 2013 (5.1 per 10,000). Thereafter, CDI incidence decreased through FY 2014
      (4.6 per 10,000). A total of 5,011 patients (17%) experienced a first recurrence
      and, of those, 1,713 (34%) experienced a second recurrence. Recurrence incidence
      increased 10-fold over the study period, from (0.1 per 10,000) in FY 2003, to
      (1.0 per 10,000) in FY 2014. Overall, 30-day mortality and median hospital length
      of stay (LOS) decreased among initial episodes over the study period. Mortality
      was higher for initial episodes (21%) compared to first recurrences (11%) and
      second recurrences (7%). Median hospital LOS was longer for first episodes (13
      days) compared to first (9 days) and second recurrences (8 days). CONCLUSIONS:
      Initial and recurrent CDI episodes increased among veterans over a 12-year
      period. Outcomes, such as mortality and hospital LOS improved in recent years;
      both of these outcomes are worse for initial CDI episodes than recurrent
      episodes.

PMID- 29216277
TI  - Immune-mediated inflammatory diseases differently affect IGRAs' accuracy for
      latent tuberculosis infection diagnosis in clinical practice.
AB  - BACKGROUND: Clinical accuracy of IGRAs remains unclear on patients with immune
      mediated inflammatory diseases (IMIDs). Here, we assess the impact of
      immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T
      SPOT.TB accuracy. METHODS: Patients with IMIDs who required latent tuberculosis
      infection (LTBI) screening were enrolled and classified into: (i) 50 patients
      with inflammatory rheumatic diseases, (ii) 50 patients with psoriasis and (iii)
      30 patients with Crohn's disease. A total of 44 healthy individuals without
      immunosuppression were also included as controls. Tuberculin skin test (TST), T
      SPOT.TB and QFN-G-IT assays were performed. IGRAs were performed following
      manufacturer's instructions. RESULTS: Immunosuppressant's intake was more
      frequent on patients with Crohn's disease and psoriasis. Positive IGRAs and TST
      results were reduced in Crohn's disease patients, whereas rate of indeterminate T
      SPOT.TB results was increased in this group with respect to the other IMIDs
      analysed and controls. When IFN-gamma response was studied, the levels of this
      cytokine after mitogen stimulation were significantly lower in Crohn's and
      inflammatory rheumatic diseases than in psoriasis. Interestingly, psoriatic
      patients were the only ones not receiving corticosteroids. Furthermore, a
      negative correlation was observed between the IFN-gamma secreted after mitogen
      stimulation and corticosteroids dose. CONCLUSIONS: IMIDs seem to negatively
      affect the clinical accuracy of IGRAs, being Crohn's disease patients the most
      affected individuals due to their concomitant drug-profile and impaired immune
      response.

PMID- 29216278
TI  - Systematic integrative analysis of gene expression identifies HNF4A as the
      central gene in pathogenesis of non-alcoholic steatohepatitis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease in the Western world, and encompasses a spectrum from simple steatosis to
      steatohepatitis (NASH). There is currently no approved pharmacologic therapy
      against NASH, partly due to an incomplete understanding of its molecular basis.
      The goal of this study was to determine the key differentially expressed genes
      (DEGs), as well as those genes and pathways central to its pathogenesis. We
      performed an integrative computational analysis of publicly available gene
      expression data in NASH from GEO (GSE17470, GSE24807, GSE37031, GSE89632). The
      DEGs were identified using GEOquery, and only the genes present in at least three
      of the studies, to a total of 190 DEGs, were considered for further analyses. The
      pathways, networks, molecular interactions, functional analyses were generated
      through the use of Ingenuity Pathway Analysis (IPA). For selected networks, we
      computed the centrality using igraph package in R. Among the statistically
      significant predicted networks (p-val < 0.05), three were of most biological
      interest: the first is involved in antimicrobial response, inflammatory response
      and immunological disease, the second in cancer, organismal injury and
      development and the third in metabolic diseases. We discovered that HNF4A is the
      central gene in the network of NASH connected to metabolic diseases and that it
      regulates HNF1A, an additional transcription regulator also involved in lipid
      metabolism. Therefore, we show, for the first time to our knowledge, that HNF4A
      is central to the pathogenesis of NASH. This adds to previous literature
      demonstrating that HNF4A regulates the transcription of genes involved in the
      progression of NAFLD, and that HNF4A genetic variants play a potential role in
      NASH progression.

PMID- 29216279
TI  - Emerging hazard effects of proton pump inhibitor on the risk of colorectal cancer
      in low-risk populations: A Korean nationwide prospective cohort study.
AB  - PURPOSE: Despite plausible mechanisms, the clinical significance of long-term
      proton pump inhibitor (PPI) use to colorectal cancer (CRC) remains unknown. The
      purpose of this study was to investigate the association between PPI use and CRC
      development. METHODS: We conducted a population-based prospective cohort study
      using the Korean nationwide claims database merged with national health
      examination data. The study cohort included a total of 451,284 participants who
      were tracked to identify cases of CRC since 2007. We assessed and standardized
      PPI use before the index date using the Defined Daily Dose system. We calculated
      the hazard ratios and their 95% confidence intervals to assess the association
      between PPI use and CRC occurrence using Cox proportional hazard regression
      models with adjustment for potential confounders. We performed subgroup analyses
      of the effect of PPI exposure on CRC development stratified by the CRC risk.
      RESULTS: There were 5,304 cases of CRC during the study period of 2,908,152
      person-years. PPI use was not associated with CRC risk overall. The incidence of
      CRC was higher among individuals who were elderly, male, more obese, and drank
      alcohol more frequently and among those who had more comorbidities. Further
      subgroup analyses revealed that the hazard effect of PPI use increased linearly
      in a dose-dependent manner with the number of CRC risk factors for which the risk
      level was considered low. CONCLUSION: Within the low-risk population, PPI use was
      associated with an increased risk of CRC, although the association did not weigh
      the effects of conventional risk factors.

PMID- 29216280
TI  - Phenotypic characterization of Synechocystis sp. PCC 6803 substrains reveals
      differences in sensitivity to abiotic stress.
AB  - Synechocystis sp. PCC 6803 is a widely used model cyanobacterium, whose
      substrains can vary on both genotype and phenotype levels. Previously described
      phenotypic variations include ability of mixotrophic growth, ability of movement
      on agar plates and variations in pigments composition or cell size. In this
      study, we report for the first time significant variation among Synechocystis
      substrains in complex cellular traits such as growth rate, photosynthesis
      efficiency, cellular dry weight and cellular composition (including protein or
      carbohydrates content). We also confirmed previously reported differences in cell
      size. Synechocystis cultures were cultivated in controlled environment of flat
      panel photobioreactors under red, blue and white light of intensities up to 790
      MUmol(photons) m-2 s-1, temperatures 23 degrees C-60 degrees C, input CO2
      concentrations ranging from 400 to 15 000 ppm and in BG11 cultivation medium with
      and without addition of NaCl. Three Synechocystis substrains were used for the
      comparative experiments: GT-L, GT-B (Brno, CZ) and PCC-B (Brno, CZ). Growth rates
      of Synechocystis GT-B were inhibited under high intensities of red light (585-670
      nm), and growth rates of both substrains GT-B and PCC-B were inhibited under
      photons of wavelengths 485-585 nm and 670-700 nm. Synechocystis GT-B was more
      sensitive to low temperatures than the other two tested substrains, and
      Synechocystis GT-L was sensitive to the presence of NaCl in the cultivation
      media. The results suggest that stress sensitivity of commonly used Synechocystis
      substrains can strongly vary, similarly as glucose tolerance or motility as
      reported previously. Our study further supports the previous statement that
      emphasizes importance of proper Synechocystis substrains selection and awareness
      of phenotypical differences among Synechocystis substrains which is crucial for
      comparative and reproducible research. This is highly relevant for studies
      related to stress physiology and development of sustainable biotechnological
      applications.

PMID- 29216281
TI  - Complete mitochondrial genome of Zeugodacus tau (Insecta: Tephritidae) and
      differentiation of Z. tau species complex by mitochondrial cytochrome c oxidase
      subunit I gene.
AB  - The tephritid fruit fly Zeugodacus tau (Walker) is a polyphagous fruit pest of
      economic importance in Asia. Studies based on genetic markers indicate that it
      forms a species complex. We report here (1) the complete mitogenome of Z. tau
      from Malaysia and comparison with that of China as well as the mitogenome of
      other congeners, and (2) the relationship of Z. tau taxa from different
      geographical regions based on sequences of cytochrome c oxidase subunit I gene.
      The complete mitogenome of Z. tau had a total length of 15631 bp for the
      Malaysian specimen (ZT3) and 15835 bp for the China specimen (ZT1), with similar
      gene order comprising 37 genes (13 protein-coding genes-PCGs, 2 rRNA genes, and
      22 tRNA genes) and a non-coding A + T-rich control region (D-loop). Based on 13
      PCGs and 15 mt-genes, Z. tau NC_027290 (China) and Z. tau ZT1 (China) formed a
      sister group in the lineage containing also Z. tau ZT3 (Malaysia). Phylogenetic
      analysis based on partial sequences of cox1 gene indicates that the taxa from
      China, Japan, Laos, Malaysia, Bangladesh, India, Sri Lanka, and Z. tau sp. A from
      Thailand belong to Z. tau sensu stricto. A complete cox1 gene (or 13 PCGs or 15
      mt-genes) instead of partial sequence is more appropriate for determining
      phylogenetic relationship.

PMID- 29216282
TI  - Sequential combined test, second trimester maternal serum markers, and
      circulating fetal cells to select women for invasive prenatal diagnosis.
AB  - From January 1st 2013 to August 31st 2016, 24408 pregnant women received the
      first trimester Combined test and contingently offered second trimester maternal
      serum screening to identify those women who would most benefit from invasive
      prenatal diagnosis (IPD). The screening was based on first trimester cut-offs of
      >=1:30 (IPD indicated), 1:31 to 1:899 (second trimester screening indicated) and
      <=1:900 (no further action), and a second trimester cut-off of >=1:250. From
      January 2014, analysis of fetal cells from peripheral maternal blood was also
      offered to women with positive screening results. For fetal Down syndrome, the
      overall detection rate was 96.8% for a false-positive rate of 2.8% resulting in
      an odds of being affected given a positive result (OAPR) of 1:11, equivalent to a
      positive predictive value (PPV) of 8.1%. Additional chromosome abnormalities were
      also identified resulting in an OAPR for any chromosome abnormality of 1:6.6 (PPV
      11.9%). For a sub-set of cases with positive contingent test results, FISH
      analysis of circulating fetal cells in maternal circulation identified 7 abnormal
      and 39 as normal cases with 100% specificity and 100% sensitivity. We conclude
      that contingent screening using conventional Combined and second trimester
      screening tests is effective but can potentially be considerably enhanced through
      the addition of fetal cell analysis.

PMID- 29216283
TI  - Association between exercise type and quality of life in a community-dwelling
      older people: A cross-sectional study.
AB  - OBJECTIVES: This study aimed to investigate the effects of three major
      representative exercises (resistance, flexibility, and walking) on quality of
      life (QoL) in a population of community-dwelling older adults. MATERIALS AND
      METHODS: This cross-sectional study used public data from the Sixth Korean
      National Health and Nutrition Examination Survey in 2014 (n = 1,586 older
      people). Demographic factors, three types of exercise, five EuroQoL subsets
      (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and
      QoL scores (EQ-VAS) were investigated. The independent associations between each
      exercise and the five QoL subsets were determined using odds ratios (OR) adjusted
      for three demographic factors (age group, sex, and area of residence), using
      multivariate logistic regression analysis. RESULTS: The EQ-VAS scores of the
      exercisers was significantly higher than those of the non-exercisers for all
      exercise types. Subjects with problems in mobility dimension performed less
      exercise of all types of than those with normal mobility (resistance: OR, 0.687;
      flexibility: OR, 0.733, and walking: OR, 0.489). The self-care dimension was
      independently correlated with flexibility (OR, 0.558) and walking (OR, 0.485).
      CONCLUSION: All types of exercisers showed higher QoL scores than non-exercisers.
      Among the QoL dimensions, mobility and self-care were independently associated
      with flexibility and walking exercise in this older people, suggesting that
      engaging in regular flexibility and walking exercise is important for achieving
      higher QoL in the older people.

PMID- 29216284
TI  - A critical assessment of the Protoaurignacian lithic technology at Fumane Cave
      and its implications for the definition of the earliest Aurignacian.
AB  - In the scenario of the spread of the anatomically modern humans (AMHs) into
      Europe, the techno-complex known as Protoaurignacian is defined by the production
      of blades and bladelets within a single and continuous stone knapping sequence
      from the same core as the result of its progressive reduction. However, the
      growing re-evaluation of some assemblages is revealing that bladelets are
      frequently obtained from independent reduction sequences, hence discouraging the
      direct application of the model developed in southwestern France. High-resolution
      regional signatures are thus needed to reconstruct a more accurate portrait of
      the AMH colonization dynamic. Northeastern Italy, with the key site of Fumane
      Cave, is one among the regions of Mediterranean Europe worthy of consideration
      for reconstructing this colonization process and its cultural dynamics. Within
      the framework of a critical discussion of the technological definition of the
      Protoaurignacian and its relationship with contemporaneous industries on a
      regional and supra-regional scale, we present the results of a detailed analysis
      of the lithic technology from units A2-A1 based on reduction sequence and
      attribute analyses. Results show that bladelets are the first goal of production
      and they do not originate from reduced blade cores but from a broad range of
      independent and simultaneous core reduction strategies. One implication is that
      the most commonly used technological trait that is said to define the
      Protoaurignacian has been over-emphasized and that the Protoaurignacian is
      technologically consistent across its geographical extent. Additional data based
      on carinated core technology imply that this techno-complex shares a common
      technological background with the Early Aurignacian and that no features are
      restricted to one of the two facies. Furthermore, the major difference between
      the Protoaurignacian and Early Aurignacian appears to be more typological in
      nature, with retouched bladelets being less common in the Early Aurignacian.

PMID- 29216285
TI  - Myocardial adaption to HI(R)T in previously untrained men with a randomized,
      longitudinal cardiac MR imaging study (Physical adaptions in Untrained on
      Strength and Heart trial, PUSH-trial).
AB  - OBJECTIVE: Although musculoskeletal effects in resistance training are well
      described, little is known about structural and functional cardiac adaption in
      formerly untrained subjects. We prospectively evaluated whether short term high
      intensity (resistance) training (HI(R)T) induces detectable morphologic cardiac
      changes in previously untrained men in a randomized controlled magnetic resonance
      imaging (MRI) study. MATERIALS AND METHODS: 80 untrained middle-aged men were
      randomly assigned to a HI(R)T-group (n = 40; 43.5+/-5.9 years) or an inactive
      control group (n = 40; 42.0+/-6.3 years). HI(R)T comprised 22 weeks of training
      focusing on a single-set to failure protocol in 2-3 sessions/week, each with 10
      13 exercises addressing main muscle groups. Repetitions were decreased from 8-10
      to 3-5 during study period. Before and after HI(R)T all subjects underwent
      physiologic examination and cardiac MRI (cine imaging, tagging). RESULTS: Indexed
      left (LV) and right ventricular (RV) volume (LV: 76.8+/-15.6 to 78.7+/-14.8
      ml/m2; RV: 77.0+/-15.5 to 78.7+/-15.1 ml/m2) and mass (LV: 55.5+/-9.7 to 57.0+/
      8.8 g/m2; RV: 14.6+/-3.0 to 15.0+/-2.9 g/m2) significantly increased with HI(R)T
      (all p<0.001). Mean LV and RV remodeling indices of HI(R)T-group did not alter
      with training (0.73g/mL and 0.19g/mL, respectively [p = 0.96 and p = 0.87]),
      indicating balanced cardiac adaption. Indexed LV (48.4+/-11.1 to 50.8+/-11.0
      ml/m2) and RV (48.5+/-11.0 to 50.6+/-10.7 ml/m2) stroke volume significantly
      increased with HI(R)T (p<0.001). Myocardial strain and strain rates did not
      change following resistance exercise. Left atrial volume at end systole slightly
      increased after HI(R)T (36.2+/-7.9 to 37.0+/-8.4 ml/m2, p = 0.411), the ratio to
      end-diastolic LV volume at baseline and post-training was unchanged (0.47 vs.
      0.47, p = 0.79). CONCLUSION: 22 weeks of HI(R)T lead to measurable, physiological
      changes in cardiac atrial and ventricular morphologic characteristics and
      function in previously untrained men. TRIAL REGRISTRATION: The PUSH-trial is
      registered at the US National Institutes of Health (ClinicalTrials.gov),
      NCT01766791.

PMID- 29216286
TI  - Migraine and risk of narcolepsy in children: A nationwide longitudinal study.
AB  - BACKGROUND: The association between migraine and narcolepsy remains
      controversial. We aim to investigate whether migraine is associated with an
      increased risk of developing narcolepsy in children. METHODS: In this
      longitudinal study, nationwide medical-claims data of pediatric patients (0-17y)
      with migraine are identified using the National Health Insurance Research
      Database (NHIRD) between 1997 and 2010 in Taiwan. Two cohorts are selected:
      migraine cases (n = 8,923) and propensity score-matched non-migraine controls (n
      = 35,692). Children with previous history of narcolepsy or headache before the
      index date are excluded. Cohorts are followed until the end of 2012, their
      withdrawal from the NHI program, or incidence of narcolepsy (ICD-9-CM: 347). Cox
      proportional hazards regression models are used to estimate hazard ratios (HRs)
      and 95% confidence intervals of developing narcolepsy in children with migraine
      compared to their non-migraine controls. RESULTS: A total of 13 incident cases
      with narcolepsy are observed during follow-up, with incidence rates of 0.1915 and
      0.0278 per 1,000 person-years in migraine and non-migraine children,
      respectively. After a mean follow-up period of 4.68 and 5.04 years in the case
      and control cohort, respectively, the former exhibited a greater risk of
      developing narcolepsy compared to the latter (adjusted hazard ratio (aHR) = 5.30,
      95% confidence interval (CI): 1.61, 17.4; p = 0.006). This finding persisted
      after controlling for potential confounders like baseline comorbidities and
      concurrent medication uptake, and in our analyses with migraine subtypes.
      CONCLUSIONS: Migraine is an independent risk factor for narcolepsy development in
      children. Further studies are needed to validate our findings and to explore the
      exact pathophysiological mechanisms linking migraine and narcolepsy.

PMID- 29216287
TI  - Transcriptomic profiles in peripheral blood between women with unexplained
      recurrent implantation failure and recurrent miscarriage and the correlation with
      endometrium: A pilot study.
AB  - AIM: To study the transcriptome profiles in the blood of recurrent implantation
      failure (RIF), recurrent miscarriage (RM) and fertile women during the window of
      implantation, and further analysis the correlation of transcriptome profiles
      between blood and endometrium. METHODS: This is an observational prospective
      study. In total 9 subjects were recruited, 3 RIF, 3 RM, and 3 controls. Paired
      samples (endometrium and peripheral blood) from the same subjects were precisely
      timed on the 7th days after luteal hormone surge (LH+7). RNA sequencing was
      applied to investigate the transcriptome profiles. RESULTS: The results of
      transcriptome in peripheral blood cannot be used to characterize women with RIF
      and unexplained RM. There was a medium level correlation between transcriptome in
      peripheral blood and endometrium during the window of implantation. CONCLUSION:
      The differential transcriptome patterns in blood are not representative of those
      in endometrium, and the blood transcriptome cannot differentiate among the women
      with RIF, RM or fertile.

PMID- 29216288
TI  - Adaptations in antagonist co-activation: Role in the repeated-bout effect.
AB  - : Eccentric exercise results in an adaptation which attenuates muscle damage from
      subsequent exercise-termed the "repeated-bout effect (RBE)." PURPOSE: Study
      examined antagonist co-activation and motor-unit recruitment strategy, assessed
      via dEMG, concomitant to the RBE. METHODS: Nine participants performed 5 sub
      maximal isometric trapezoid (ramp-up, hold, ramp-down) contractions at force
      levels corresponding to 50% and 80% of maximal isometric strength (MVC). Surface
      EMG signals of the biceps brachii were decomposed into individual motor-unit
      action potential trains. The relationship between mean firing rate (MFR) of each
      motor-unit and its recruitment threshold (RT) was examined using linear
      regression. Eccentric exercise was then performed until biceps brachii MVC had
      decreased by ~40%. Surface EMG of the biceps and triceps were collected during
      eccentric exercise. MVC, range-of-motion (ROM), and delayed onset muscle soreness
      (DOMS) were measured 24-hours, 72-hours, and 1-week following eccentric exercise.
      Three weeks later all procedures were repeated. RESULTS: Changes in MVC (-32+/
      14% vs -25+/-10%; p = 0.034), ROM (-11% vs 6%; p = 0.01), and DOMS (31.0+/-19mm
      vs 19+/-12mm; p = 0.015) were attenuated following the second bout of exercise.
      Triceps EMG was reduced (16.8+/-9.5% vs. 12.6+/-7.2%; p = 0.03) during the second
      bout of eccentric exercise. The slope (-0.60+/-0.13 vs -0.70+/-0.18; p = 0.029)
      and y-intercept (46.5+/-8.3 vs 53.3+/-8.8; p = 0.020) of the MFR vs. RT
      relationship was altered during contractions at 80% of MVC prior to the second
      bout of eccentric exercise. No changes were observed at 50% of MVC. CONCLUSION: A
      reduction in antagonist co-activation during the second bout of eccentric
      exercise suggests less total force was required to move an identical external
      load. This finding is supported by the increased negative slope coefficient and
      an increased y-intercept of the linear relationship between RT and MFR.

PMID- 29216289
TI  - Effects of load carriage on physiological determinants in adventure racers.
AB  - Adventure racing athletes need run carrying loads during the race. A better
      understanding of how different loads influence physiological determinants in
      adventure racers could provide useful insights to gauge training interventions to
      improve running performance. We compare the maximum oxygen uptake (VO2max), the
      cost of transport (C) and ventilatory thresholds of twelve adventure running
      athletes at three load conditions: unloaded, 7 and 15% of body mass. Twelve
      healthy men experienced athletes of Adventure Racing (age 31.3 +/- 7.7 years,
      height 1.81 +/- 0.05 m, body mass 75.5 +/- 9.1 kg) carried out three maximal
      progressive (VO2max protocol) and three submaximal constant-load (running cost
      protocol) tests, defined in the following quasi-randomized conditions: unloaded,
      7% and, 15% of body mass. The VO2max (unload: 59.7 +/- 5.9; 7%: 61.7 +/- 6.6 and
      15%: 64.6 +/- 5.4 ml kg-1 min-1) did not change among the conditions. While the
      7% condition does neither modify the C nor the ventilatory thresholds, the 15%
      condition resulted in a higher C (5.2 +/- 0.9 J kg-1 m-1; P = 0.001; d = 1.48)
      than the unloaded condition (4.0 +/- 0.7 J kg-1 m-1). First ventilatory threshold
      was greater at 15% than control condition (+15.5%; P = 0.003; d = 1.44).
      Interestingly, the velocities on the severe-intensity domain (between second
      ventilatory threshold and VO2max) were reduced 1% equivalently to 1% increasing
      load (relative to body mass). The loading until 15% of body mass seems to affect
      partially the crucial metabolic and ventilatory parameters, specifically the C
      but not the VO2max. These findings are compatible with the concept that
      interventions that enhance running economy with loads may improve the running
      performance of adventure racing's athletes.

PMID- 29216290
TI  - Analysis of area level and unit level models for small area estimation in forest
      inventories assisted with LiDAR auxiliary information.
AB  - Forest inventories require estimates and measures of uncertainty for
      subpopulations such as management units. These units often times hold a small
      sample size, so they should be regarded as small areas. When auxiliary
      information is available, different small area estimation methods have been
      proposed to obtain reliable estimates for small areas. Unit level empirical best
      linear unbiased predictors (EBLUP) based on plot or grid unit level models have
      been studied more thoroughly than area level EBLUPs, where the modelling occurs
      at the management unit scale. Area level EBLUPs do not require a precise plot
      positioning and allow the use of variable radius plots, thus reducing fieldwork
      costs. However, their performance has not been examined thoroughly. We compared
      unit level and area level EBLUPs, using LiDAR auxiliary information collected for
      inventorying 98,104 ha coastal coniferous forest. Unit level models were
      consistently more accurate than area level EBLUPs, and area level EBLUPs were
      consistently more accurate than field estimates except for large management units
      that held a large sample. For stand density, volume, basal area, quadratic mean
      diameter, mean height and Lorey's height, root mean squared errors (rmses) of
      estimates obtained using area level EBLUPs were, on average, 1.43, 2.83, 2.09,
      1.40, 1.32 and 1.64 times larger than those based on unit level estimates,
      respectively. Similarly, direct field estimates had rmses that were, on average,
      1.37, 1.45, 1.17, 1.17, 1.26, and 1.38 times larger than rmses of area level
      EBLUPs. Therefore, area level models can lead to substantial gains in accuracy
      compared to direct estimates, and unit level models lead to very important gains
      in accuracy compared to area level models, potentially justifying the additional
      costs of obtaining accurate field plot coordinates.

PMID- 29216291
TI  - Correction: Interactive and Independent Associations between the Socioeconomic
      and Objective Built Environment on the Neighbourhood Level and Individual Health:
      A Systematic Review of Multilevel Studies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0123456.].

PMID- 29216292
TI  - Water consumption, grain yield, and water productivity in response to field water
      management in double rice systems in China.
AB  - Rice cultivation has been challenged by increasing food demand and water
      scarcity. We examined the responses of water use, grain yield, and water
      productivity to various modes of field water managements in Chinese double rice
      systems. Four treatments were studied in a long-term field experiment (1998
      2015): continuous flooding (CF), flooding-midseason drying-flooding (F-D-F),
      flooding-midseason drying-intermittent irrigation without obvious standing water
      (F-D-S), and flooding-rain-fed (F-RF). The average precipitation was 483 mm in
      early-rice season and 397 mm in late-rice season. The irrigated water for CF, F-D
      F, F-D-S, and F-RF, respectively, was 263, 340, 279, and 170 mm in early-rice
      season, and 484, 528, 422, and 206 mm in late-rice season. Grain yield for CF, F
      D-F, F-D-S, and F-RF, respectively, was 4,722, 4,597, 4,479, and 4,232 kgha-1 in
      early-rice season, and 5,420, 5,402, 5,366, and 4,498 kgha-1 in late-rice season.
      Compared with CF, F-D-F consumed more irrigated water, which still decreased
      grain yield, leading to a decrease in water productivity by 25% in early-rice
      season and by 8% in late-rice season. Compared with F-D-F, F-D-S saved much
      irrigated water with a small yield reduction, leading to an increase in water
      productivity by 22% in early-rice season and by 26% in late-rice season. The
      results indicate that CF is best for early-rice and FDS is best for late-rice in
      terms of grain yield and water productivity.

PMID- 29216293
TI  - Correction: Do weaner pigs need in-feed antibiotics to ensure good health and
      welfare?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185622.].

PMID- 29216294
TI  - Correction: Clinical validation of a highly sensitive assay to detect EGFR
      mutations in plasma cell-free DNA from patients with advanced lung
      adenocarcinoma.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183331.].

PMID- 29216296
TI  - Correction: The potential role of kelp forests on iodine speciation in coastal
      seawater.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180755.].

PMID- 29216295
TI  - Alpha-1 antichymotrypsin is involved in astrocyte injury in concert with arginine
      vasopressin during the development of acute hepatic encephalopathy.
AB  - BACKGROUND AND AIMS: We developed a bio-artificial liver (BAL) using a radial
      flow bioreactor and rescued mini-pig models with lethal acute liver failure
      (ALF). The point of the rescue is the recovery from hepatic encephalopathy (HE).
      HE on ALF has sometimes resulted in brain death following brain edema with
      astrocyte swelling. Several factors, including ammonia and glutamine, have been
      reported to induce astrocyte swelling and injury. However, many clinicians
      believe that there are any other factors involved in the development of HE.
      Therefore, the aim of this study was to identify novel HE-inducible factors,
      particularly those inducing astrocyte dysfunction. METHODS: Mini-pig plasma
      samples were collected at three time points: before the administration of toxins
      (alpha-amanitin and LPS), when HE occurred after the administration of toxins,
      and after treatment with extracorporeal circulation (EC) by the BAL. To identify
      the causative factors of HE, each plasma sample was subjected to a comparative
      proteome analysis with two-dimensional gel electrophoresis and mass spectrometry.
      To assess the direct effects of candidate factors on the astrocyte function and
      injury, in vitro experiments with human astrocytes were performed. RESULTS: Using
      a proteome analysis, we identified alpha-1 antichymotrypsin (ACT), which was
      increased in plasma samples from mini-pigs with HE and decreased in those after
      treatment with EC by BAL. In in vitro experiments with human astrocytes, ACT
      showed growth-inhibitory and cytotoxic effects on astrocytes. In addition, the
      expression of water channel protein aquaporin-4, which is induced in injured
      astrocytes, was increased following ACT treatment. Interestingly, these effects
      of ACT were additively enhanced by adding arginine-vasopressin (AVP) and were
      canceled by adding an AVP receptor antagonist. CONCLUSIONS: These results suggest
      that ACT is involved in astrocyte injury and dysfunction in concert with AVP
      during the development of acute HE.

PMID- 29216297
TI  - Skn-1a/Pou2f3 functions as a master regulator to generate Trpm5-expressing
      chemosensory cells in mice.
AB  - Transient receptor potential channel M5 (Trpm5)-expressing cells, such as sweet,
      umami, and bitter taste cells in the oropharyngeal epithelium, solitary
      chemosensory cells in the nasal respiratory epithelium, and tuft cells in the
      small intestine, that express taste-related genes function as chemosensory cells.
      Previous studies demonstrated that Skn-1a/Pou2f3, a POU homeodomain transcription
      factor is expressed in these Trpm5-expressing chemosensory cells, and is
      necessary for their generation. Trpm5-expressing cells have recently been found
      in trachea, auditory tube, urethra, thymus, pancreatic duct, stomach, and large
      intestine. They are considered to be involved in protective responses to
      potential hazardous compounds as Skn-1a-dependent bitter taste cells, respiratory
      solitary chemosensory cells, and intestinal tuft cells are. In this study, we
      examined the expression and function of Skn-1a/Pou2f3 in Trpm5-expressing cells
      in trachea, auditory tube, urethra, thymus, pancreatic duct, stomach, and large
      intestine. Skn-1a/Pou2f3 is expressed in a majority of Trpm5-expressing cells in
      all tissues examined. In Skn-1a/Pou2f3-deficient mice, the expression of Trpm5 as
      well as marker genes for Trpm5-expressing cells were absent in all tested
      tissues. Immunohistochemical analyses demonstrated that two types of microvillous
      cells exist in trachea, urethra, and thymus, Trpm5-positive and Trpm5-negative
      cells. In Skn-1a/Pou2f3-deficient mice, a considerable proportion of Trpm5
      negative and villin-positive microvillous cells remained present in these
      tissues. Thus, we propose that Skn-1a/Pou2f3 is the master regulator for the
      generation of the Trpm5-expressing microvillous cells in multiple tissues.

PMID- 29216298
TI  - Correction: Emotional cue validity effects: The role of neurocognitive responses
      to emotion.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179714.].

PMID- 29216299
TI  - Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding
      and a use in a mammalian expression system with a RNA-vector.
AB  - B18R protein of Vaccinia virus binds to type I interferons and inhibits
      activation of interferon-mediated signal transduction. Cells which have
      unimpaired interferon signaling such as primary cell cultures or some
      industrially important cell lines are capable of development of an antiviral
      state. An establishment of the antiviral state limits replication of RNA-viruses
      and can suppress replication of RNA vectors. The interferon inhibitor B18R
      effectively prevents the establishment of the antiviral state. For this reason,
      B18R has become a ubiquitous component of protocols for epigenetic reprogramming
      which use transfections of RNA replicons or mRNA. Despite wide practical
      applicability, commercially available B18R is predominantly produced in cell
      cultures and little information has been published on a production and use of
      bacterially expressed B18R. Objectives of this study were to produce B18R in an
      E.coli expression system and to confirm the product's biological activity by
      using it to maintain RNA-vectors in cell cultures capable of the antiviral state.
      The described method allows the expression and efficient refolding to obtain 10
      100 mg of B18R from a small-scale culture and the production process is
      economically attractive compared to a use of an eukaryotic expression. To check
      for a presence of the biological activity of bacterially-expressed B18R the
      protein was used to support persistence of an autonomously replicating RNA-vector
      in a cell culture which is capable of the antiviral state. A RNA-containing
      virus, Venezuelan equine encephalitis virus (VEE) can serve as an efficient
      vector for heterologous expression in cell cultures, although its replication is
      sensitive to the effects of type I interferons which limit a range of cell lines
      for a use with this vector. The VEE replicon was utilized to direct an expression
      of recombinant human granulocyte colony stimulating factor (G-CSF). The producing
      replicon could persist in HEK293 cells for sufficiently long time only in
      presence of B18R, whereas addition of B18R not only allowed persistence of the
      replicon but also increased production from the replicon. A model product
      granulocyte colony stimulating factor accumulated to 35.5 MUg/ml during a 7 day
      experiment. This work describes efficacious expression and refolding of the viral
      cytokine inhibitor and demonstrates a utility of bacterially-expressed B18R.

PMID- 29216300
TI  - Impacts of active school design on school-time sedentary behavior and physical
      activity: A pilot natural experiment.
AB  - BACKGROUND: Children spend a significant portion of their days in sedentary
      behavior (SB) and on average fail to engage in adequate physical activity (PA).
      The school built environment may influence SB and PA, but research is limited.
      This natural experiment evaluated whether an elementary school designed to
      promote movement impacted students' school-time SB and PA. METHODS:
      Accelerometers measured SB and PA at pre and post time-points in an intervention
      group who moved to the new school (n = 21) and in a comparison group experiencing
      no school environmental change (n = 20). Difference-in-difference (DD) analysis
      examined SB and PA outcomes in these groups. Measures were also collected post
      intervention from an independent, grade-matched group of students in the new
      school (n = 21). RESULTS: As expected, maturational increases in SB were
      observed. However, DD analysis estimated that the intervention attenuated
      increase in SB by 81.2 +/- 11.4 minutes/day (p<0.001), controlling for time in
      moderate to vigorous physical activity (MVPA). The intervention was also
      estimated to increase daily number of breaks from SB by 23.4 +/- 2.6 (p < .001)
      and to increase light physical activity (LPA) by 67.7 +/- 10.7 minutes/day
      (p<0.001). However, the intervention decreased MVPA by 10.3 +/- 2.3 minutes/day
      (p<0.001). Results of grade-matched independent samples analysis were similar,
      with students in the new vs. old school spending 90.5 +/- 16.1 fewer minutes/day
      in SB, taking 21.1 +/- 2.7 more breaks from SB (p<0.001), and spending 64.5 +/-
      14.8 more minutes in LPA (p<0.001), controlling for time in MVPA. Students in the
      new school spent 13.1 +/- 2.7 fewer minutes in MVPA (p<0.001) than their
      counterparts in the old school. CONCLUSIONS: This pilot study found that active
      school design had beneficial effects on SB and LPA, but not on MVPA. Mixed
      results point to a need for active classroom design strategies to mitigate SB,
      and quick access from classrooms to areas permissive of high-intensity activities
      to promote MVPA. Integrating active design with programs/policies to promote PA
      may yield greatest impact on PA of all intensities.

PMID- 29216301
TI  - Chronic dietary supplementation with soy protein improves muscle function in
      rats.
AB  - Athletes as well as elderly or hospitalized patients use dietary protein
      supplementation to maintain or grow skeletal muscle. It is recognized that high
      quality protein is needed for muscle accretion, and can be obtained from both
      animal and plant-based sources. There is interest to understand whether these
      sources differ in their ability to maintain or stimulate muscle growth and
      function. In this study, baseline muscle performance was assessed in 50 adult
      Sprague-Dawley rats after which they were assigned to one of five semi-purified
      "Western" diets (n = 10/group) differing only in protein source, namely 19 kcal%
      protein from either milk protein isolate (MPI), whey protein isolate (WPI), soy
      protein isolate (SPI), soy protein concentrate (SPC) or enzyme-treated soy
      protein (SPE). The diets were fed for 8 weeks at which point muscle performance
      testing was repeated and tissues were collected for analysis. There was no
      significant difference in food consumption or body weights over time between the
      diet groups nor were there differences in terminal organ and muscle weights or in
      serum lipids, creatinine or myostatin. Compared with MPI-fed rats, rats fed WPI
      and SPC displayed a greater maximum rate of contraction using the in vivo measure
      of muscle performance (p<0.05) with increases ranging from 13.3-27.5% and 22.8
      29.5%, respectively at 60, 80, 100 and 150 Hz. When the maximum force was
      normalized to body weight, SPC-fed rats displayed increased force compared to MPI
      (p<0.05), whereas when normalized to gastrocnemius weight, WPI-fed rats displayed
      increased force compared to MPI (p<0.05). There was no difference between groups
      using in situ muscle performance. In conclusion, soy protein consumption, in high
      fat diet, resulted in muscle function comparable to whey protein and improved
      compared to milk protein. The benefits seen with soy or whey protein were
      independent of changes in muscle mass or fiber cross-sectional area.

PMID- 29216302
TI  - Resource utilization in lung cancer diagnostic procedures: Current use and budget
      consequences.
AB  - OBJECTIVES: The main objective of this study is to determine the current use of
      lung cancer diagnostic procedures in two large hospitals in the Netherlands, to
      explore deviations in guideline adherence between the hospitals, and to estimate
      the budget impact of the diagnostic work-up as well as the over- and
      underutilization. MATERIALS & METHODS: A state transition model for the
      diagnostic pathway for lung cancer patients was developed using existing clinical
      practice guidelines (CPG) combined with a systematic literature. In addition to
      the CPGs depicting current practice, diagnostic utilization was gathered in two
      large hospitals representing an academic tertiary care hospital and a large
      regional teaching hospital for patients, who were selected from the Netherlands
      cancer registry. RESULTS: The total population consisted of 376 patients with
      lung cancer. Not in all cases the guideline was followed, for instance in the
      usage of MR brain with stage III lung cancer patients (n = 70). The state
      transition model predicts an average budget impact for the diagnostic pathway per
      patient estimated of ? 2496 in the academic tertiary care hospital and ? 2191 in
      the large regional teaching hospital. CONCLUSION: The adherence to the CPG's
      differed between hospitals, which questions the adherence to CPG's in general.
      Adherence to CPG's could lead to less costs in the diagnostic pathway for lung
      cancer patients.

PMID- 29216304
TI  - Correction: The impact of the Brazilian family health on selected primary care
      sensitive conditions: A systematic review.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182336.].

PMID- 29216303
TI  - Three-dimensional self-gated cardiac MR imaging for the evaluation of myocardial
      infarction in mouse model on a 3T clinical MR system.
AB  - PURPOSE: To develop and assess a three-dimensional (3D) self-gated technique for
      the evaluation of myocardial infarction (MI) in mouse model without the use of
      external electrocardiogram (ECG) trigger and respiratory motion sensor on a 3T
      clinical MR system. METHODS: A 3D T1-weighted GRE sequence with stack-of-stars
      sampling trajectories was developed and performed on six mice with MIs that were
      injected with a gadolinium-based contrast agent at a 3T clinical MR system.
      Respiratory and cardiac self-gating signals were derived from the Cartesian
      mapping of the k-space center along the partition encoding direction by bandpass
      filtering in image domain. The data were then realigned according to the
      predetermined self-gating signals for the following image reconstruction. In
      order to accelerate the data acquisition, image reconstruction was based on
      compressed sensing (CS) theory by exploiting temporal sparsity of the
      reconstructed images. In addition, images were also reconstructed from the same
      realigned data by conventional regridding method for demonstrating the
      advantageous of the proposed reconstruction method. Furthermore, the accuracy of
      detecting MI by the proposed method was assessed using histological analysis as
      the standard reference. Linear regression and Bland-Altman analysis were used to
      assess the agreement between the proposed method and the histological analysis.
      RESULTS: Compared to the conventional regridding method, the proposed CS method
      reconstructed images with much less streaking artifact, as well as a better
      contrast-to-noise ratio (CNR) between the blood and myocardium (4.1 +/- 2.1 vs.
      2.9 +/- 1.1, p = 0.031). Linear regression and Bland-Altman analysis demonstrated
      that excellent correlation was obtained between infarct sizes derived from the
      proposed method and histology analysis. CONCLUSION: A 3D T1-weighted self-gating
      technique for mouse cardiac imaging was developed, which has potential for
      accurately evaluating MIs in mice at 3T clinical MR system without the use of
      external ECG trigger and respiratory motion sensor.

PMID- 29216305
TI  - Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus,
      Streptococcus thermophilus and Enterococcus faecalis and their related products
      on human colonic smooth muscle in vitro.
AB  - OBJECTIVE: To investigate the effects of four strains, generally used in clinic,
      including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus
      thermophilus and Enterococcus faecalis, and their related products on human
      colonic smooth muscle in vitro. METHODS: Human colonic circular muscle strips
      obtained from disease-free margins of resected segments from 25 patients with
      colorectal cancer were isometrically examined in a constant-temperature organ
      bath and exposed to different concentrations of living bacteria, sonicated cell
      fractions and cell-free supernatant (CFS). The area under the curve (AUC)
      representing the contractility of smooth muscle strips was calculated. RESULTS:
      (1) The four living probiotics inhibited the contractility of human colonic
      muscle strips only at high concentration (1010 CFUs/mL, all P<0.05). (2) The
      sonicated cell fractions from the four probiotics obviously inhibited human
      colonic smooth muscle strips in a dose-dependent manner (P<0.01). (3) The CFS
      from the four probiotics also inhibited colonic smooth muscle strips in a dose
      dependent manner (all P<0.05). (4) The inhibition effect of CFS from
      Streptococcus thermophilus and Enterococcus faecalis decreased obviously when
      pretreated with NG-nitro-L-arginine (L-NNA, 10-5 mol/L) (P<0.05), but not the
      Bifidobacterium longum and Lactobacillus acidophilus (P>0.05). CONCLUSION: Four
      common probiotics related products, including the sonicated cell fractions and
      the CFS, obviously inhibited human colonic smooth muscles strips contraction in a
      dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL)
      can inhibit the colonic smooth muscles strips contraction. The NO pathway may be
      partly involved in the inhibitory effect of CFS from Streptococcus thermophilus
      and Enterococcus faecalis.

PMID- 29216306
TI  - Correction: Vibrio aphrogenes sp. nov., in the Rumoiensis clade isolated from a
      seaweed.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180053.].

PMID- 29216308
TI  - Candida albicans orf19.3727 encodes phytase activity and is essential for human
      tissue damage.
AB  - Candida albicans is a clinically important human fungal pathogen. We previously
      identified the presence of cell-associated phytase activity in C. albicans. Here,
      we reveal for the first time, that orf19.3727 contributes to phytase activity in
      C. albicans and ultimately to its virulence potency. Compared with its wild type
      counterpart, disruption of C. albicans orf19.3727 led to decreased phytase
      activity, reduced ability to form hyphae, attenuated in vitro adhesion, and
      reduced ability to penetrate human epithelium, which are the major virulence
      attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in
      fungal pathogenesis. Further, our data uncover a putative novel strategy for anti
      Candidal drug design through inhibition of phytase activity of this common
      pathogen.

PMID- 29216307
TI  - Audio-motor but not visuo-motor temporal recalibration speeds up sensory
      processing.
AB  - Perception of synchrony between one's own action (a finger tap) and the sensory
      feedback thereof (a visual flash or an auditory pip) can be recalibrated after
      exposure to an artificially inserted delay between them (temporal recalibration
      effect: TRE). TRE might be mediated by a compensatory shift of motor timing (when
      did I tap?) and/or the sensory timing of the feedback (when did I hear/see the
      feedback?). To examine this, we asked participants to voluntarily tap their index
      finger at a constant pace while receiving visual or auditory feedback (a flash or
      pip) that was either synced or somewhat delayed relative to the tap. Following
      this exposure phase, they then performed a simple reaction time (RT) task to
      measure the sensory timing of the exposure stimulus, and a sensorimotor
      synchronization (SMS) task (tapping in synchrony with a flash or pip as pacing
      stimulus) to measure the point of subjective synchrony between the tap and pacing
      stimulus. The results showed that after exposure to delayed auditory feedback,
      participants tapped earlier (~21.5 ms) relative to auditory pacing stimuli (=
      temporal recalibration) and reacted faster (~5.6 ms) to auditory stimuli. For
      visual exposure and test stimuli, there were no such compensatory effects. These
      results indicate that adjustments of audio-motor synchrony can to some extent be
      explained by a change in the speed of auditory sensory processing. We discuss
      this in terms of an attentional modulation of sensory processing.

PMID- 29216309
TI  - Coronary-to-pulmonary artery fistula in adults: Evaluation with thallium-201
      myocardial perfusion SPECT.
AB  - OBJECTIVES: With the increasing use of multi-detector CT, the number of detected
      cases with coronary-to-pulmonary artery fistula (CPAF) has increased. Several
      previous studies reported severe cases of angina, but no appropriate tests to
      evaluate myocardial perfusion for patients with CPAF have been established. We
      evaluated the hemodynamic characteristics of CPAF using thallium-201 (Tl-201)
      single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Tl-201
      SPECT was performed in 17 patients with CPAF, but without evidence of coronary
      artery disease on coronary computed tomography angiography (CCTA) (age, 58.5+/
      13.3 years; 8 men). Quantitative analysis of scintigraphic data was performed.
      Additionally, perfusion abnormalities were compared with CCTA findings. Medical
      records were obtained to define clinical data, diagnostic findings, symptoms,
      management, follow-up data, and major adverse cardiac events (MACE). RESULTS: Six
      patients (35.2%) showed perfusion abnormalities on SPECT studies and could be
      classified as follows: 3 patients, no reversible ischemia (3/17, 17.6%); 1
      patient, mild ischemia (1/17, 5.8%); and 2 patients, moderate ischemia (2/17,
      11.7%). During the follow-up, ten patients (58.8%) improved under medical
      management and 5 patients (29.4%) underwent surgical ligation for CPAF with
      symptomatic improvement in 4 patients. Seven patients performed follow-up
      myocardial perfusion SPECT, and symptomatic improvement correlated well with
      scintigraphic perfusion improvement in 6 patients No MACE was observed. CLINICAL
      SIGNIFICANCE: Tl-201 myocardial perfusion SPECT might be useful for determining
      the hemodynamic status and for risk stratification in patients with CPAF.

PMID- 29216310
TI  - Gbm.auto: A software tool to simplify spatial modelling and Marine Protected Area
      planning.
AB  - BOOSTED REGRESSION TREES. EXCELLENT FOR DATA-POOR SPATIAL MANAGEMENT BUT HARD TO
      USE: Marine resource managers and scientists often advocate spatial approaches to
      manage data-poor species. Existing spatial prediction and management techniques
      are either insufficiently robust, struggle with sparse input data, or make
      suboptimal use of multiple explanatory variables. Boosted Regression Trees
      feature excellent performance and are well suited to modelling the distribution
      of data-limited species, but are extremely complicated and time-consuming to
      learn and use, hindering access for a wide potential user base and therefore
      limiting uptake and usage. BRTS AUTOMATED AND SIMPLIFIED FOR ACCESSIBLE GENERAL
      USE WITH RICH FEATURE SET: We have built a software suite in R which integrates
      pre-existing functions with new tailor-made functions to automate the processing
      and predictive mapping of species abundance data: by automating and greatly
      simplifying Boosted Regression Tree spatial modelling, the gbm.auto R package
      suite makes this powerful statistical modelling technique more accessible to
      potential users in the ecological and modelling communities. The package and its
      documentation allow the user to generate maps of predicted abundance, visualise
      the representativeness of those abundance maps and to plot the relative influence
      of explanatory variables and their relationship to the response variables.
      Databases of the processed model objects and a report explaining all the steps
      taken within the model are also generated. The package includes a previously
      unavailable Decision Support Tool which combines estimated escapement biomass
      (the percentage of an exploited population which must be retained each year to
      conserve it) with the predicted abundance maps to generate maps showing the
      location and size of habitat that should be protected to conserve the target
      stocks (candidate MPAs), based on stakeholder priorities, such as the
      minimisation of fishing effort displacement. GBM.AUTO FOR MANAGEMENT IN VARIOUS
      SETTINGS: By bridging the gap between advanced statistical methods for species
      distribution modelling and conservation science, management and policy, these
      tools can allow improved spatial abundance predictions, and therefore better
      management, decision-making, and conservation. Although this package was built to
      support spatial management of a data-limited marine elasmobranch fishery, it
      should be equally applicable to spatial abundance modelling, area protection, and
      stakeholder engagement in various scenarios.

PMID- 29216312
TI  - Correction: Long-distance connections in the Copper Age: New evidence from the
      Alpine Iceman's copper axe.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179263.].

PMID- 29216311
TI  - Amelioration of sexual behavior and motor activity deficits in a castrated rodent
      model with a selective androgen receptor modulator SARM-2f.
AB  - Sarcopenia and cachexia present characteristic features of a decrease in skeletal
      muscle mass and strength, anorexia, and lack of motivation. Treatments for these
      diseases have not yet been established, although selective androgen receptor
      modulators (SARMs) are considered as therapeutic targets. We previously reported
      that a novel SARM compound, SARM-2f, exhibits anabolic effect on muscles, with
      less stimulatory effect on prostate weight compared with testosterone, in rat
      Hershberger assays and cancer cachexia models. In this study, we studied the
      mechanism of action for SARM-2f selectivity and also assessed whether the muscle
      increase by this compound might lead to improvement of muscle function and
      physical activity. First, we examined the tissue distribution of SARM-2f. Tissue
      concentration was 1.2-, 1.6-, and 1.9-fold as high as the plasma concentration in
      the levator ani muscle, brain, and prostate, respectively. This result showed
      that the tissue-selective pharmacological effect did not depend on SARM-2f
      concentration in the tissues. The ability of SARM-2f to influence androgen
      receptor (AR)-mediated transcriptional activation was examined by reporter assays
      using human normal prostate epithelial cells (PrEC) and skeletal muscle cells
      (SKMC). SARM-2f exerted higher activity against AR in SKMC than in PrEC.
      Mammalian two hybrid assays showed different co-factor recruitment patterns
      between SARM-2f and dihydrotestosterone. Next, we studied the effect of SARM-2f
      on motivation and physical functions such as sexual behavior and motor activities
      in castrated rat or mouse models. SARM-2f restored the sexual behavior that was
      lost by castration in male rats. SARM-2f also increased voluntary running
      distance and locomotor activities. These results suggest that tissue-specific AR
      regulation by SARM-2f, but not tissue distribution, might account for its tissue
      specific androgenic effect, and that the muscle mass increase by SARM-2f leads to
      improvement of physical function. Together, these findings suggest that SARM-2f
      might represent an effective treatment for sarcopenia and cachexia.

PMID- 29216313
TI  - Correction: Elongation Factor Tu and Heat Shock Protein 70 Are Membrane
      Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong
      Immune Response in Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0161170.].

PMID- 29216314
TI  - Clinical outcomes in patients treated for coronary in-stent restenosis with drug
      eluting balloons: Impact of high platelet reactivity.
AB  - BACKGROUND: The impact of high platelet reactivity (HPR) on clinical outcomes
      after elective percutaneous coronary interventions (PCI) with drug-eluting
      balloons (DEB) due to in-stent restenosis (ISR) is unknown. OBJECTIVE: We sought
      to evaluate the prognostic importance of HPR together with conventional risk
      factors in patients treated with DEB. METHODS: Patients treated with DEB due to
      ISR were enrolled in a single-centre, prospective registry between October 2009
      and March 2015. Only patients with recent myocardial infarction (MI) received
      prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test
      >46U with the Multiplate assay and no adjustments were done based on results. The
      primary endpoint of the study was a composite of cardiovascular mortality, MI,
      any revascularization or stroke during one-year follow-up. RESULTS: 194 stable
      angina patients were recruited of whom 90% were treated with clopidogrel.
      Clinical characteristics and procedural data were available for all patients;
      while platelet function testing was performed in 152 subjects of whom 32 (21%)
      had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45;
      CI: 1.01-5.92; p = 0.03). The difference was primarily driven by a higher risk
      for revascularization and MI. According to the multivariate analysis, HPR
      remained a significant, independent predictor of the primary endpoint (HR: 2.88;
      CI: 1.02-8.14; p = 0.04), while total DEB length and statin treatment were other
      independent correlates of the primary outcome. CONCLUSION: HPR was found to be an
      independent predictor of repeat revascularization and MI among elective patients
      with ISR undergoing PCI with DEB.

PMID- 29216316
TI  - Correction: Low magnitude high frequency vibration promotes adipogenic
      differentiation of bone marrow stem cells via P38 MAPK signal.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0172954.].

PMID- 29216315
TI  - The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal transport
      to promote neuroinvasion.
AB  - A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination
      of infection to sensory and autonomic ganglia of the peripheral nervous system
      following an initial exposure at mucosal surfaces. The peripheral ganglia serve
      as the latent virus reservoir and the source of recurrent infections such as cold
      sores (herpes simplex virus type I) and shingles (varicella zoster virus).
      However, the means by which these viruses routinely invade the nervous system is
      not fully understood. We report that an internal virion component, the pUL37
      tegument protein, has a surface region that is an essential neuroinvasion
      effector. Mutation of this region rendered herpes simplex virus type 1 (HSV-1)
      and pseudorabies virus (PRV) incapable of spreading by retrograde axonal
      transport to peripheral ganglia both in culture and animals. By monitoring the
      axonal transport of individual viral particles by time-lapse fluorescence
      microscopy, the mutant viruses were determined to lack the characteristic
      sustained intracellular capsid motion along microtubules that normally traffics
      capsids to the neural soma. Consistent with the axonal transport deficit, the
      mutant viruses did not reach sites of latency in peripheral ganglia, and were
      avirulent. Despite this, viral propagation in peripheral tissues and in cultured
      epithelial cell lines remained robust. Selective elimination of retrograde
      delivery to the nervous system has long been sought after as a means to develop
      vaccines against these ubiquitous, and sometimes devastating viruses. In support
      of this potential, we find that HSV-1 and PRV mutated in the effector region of
      pUL37 evoked effective vaccination against subsequent nervous system challenges
      and encephalitic disease. These findings demonstrate that retrograde axonal
      transport of the herpesviruses occurs by a virus-directed mechanism that operates
      by coordinating opposing microtubule motors to favor sustained retrograde
      delivery of the virus to the peripheral ganglia. The ability to selectively
      eliminate the retrograde axonal transport mechanism from these viruses will be
      useful in trans-synaptic mapping studies of the mammalian nervous system, and
      affords a new vaccination paradigm for human and veterinary neurotropic
      herpesviruses.

PMID- 29216317
TI  - Novel Wolbachia-transinfected Aedes aegypti mosquitoes possess diverse fitness
      and vector competence phenotypes.
AB  - Wolbachia pipientis from Drosophila melanogaster (wMel) is an endosymbiotic
      bacterium that restricts transmission of human pathogenic flaviviruses and
      alphaviruses, including dengue, Zika, and chikungunya viruses, when introduced
      into the mosquito vector Aedes aegypti. To date, wMel-infected Ae. aegypti have
      been released in field trials in 5 countries to evaluate the effectiveness of
      this strategy for disease control. Despite the success in establishing wMel
      infected mosquitoes in wild populations, and the well-characterized antiviral
      capabilities of wMel, transinfecting different or additional Wolbachia strains
      into Ae. aegypti may improve disease impact, and perhaps more importantly, could
      provide a strategy to account for the possible evolution of resistant
      arboviruses. Here, we report the successful transinfection of Ae. aegypti with
      the Wolbachia strains wMelCS (D. melanogaster), wRi (D. simulans) and wPip (Culex
      quinquefasciatus) and assess the effects on Ae. aegypti fitness, cytoplasmic
      incompatibility, tissue tropism and pathogen blocking in a laboratory setting.
      The results demonstrate that wMelCS provides a similar degree of protection
      against dengue virus as wMel following an infectious blood meal, and
      significantly reduces viral RNA levels beyond that of wMel following a direct
      challenge with infectious virus in mosquitoes, with no additional fitness cost to
      the host. The protection provided by wRi is markedly weaker than that of wMelCS,
      consistent with previous characterisations of these lines in Drosophila, while
      wPip was found to substantially reduce the fitness of Ae. aegypti. Thus, we
      determine wMelCS as a key candidate for further testing in field-relevant fitness
      tests and viremic blood feeding challenges in a clinical setting to determine if
      it may represent an alternative Wolbachia strain with more desirable attributes
      than wMel for future field testing.

PMID- 29216319
TI  - Correction: Bioactive properties of faveleira (Cnidoscolus quercifolius) seeds,
      oil and press cake obtained during oilseed processing.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183935.].

PMID- 29216318
TI  - Reproducibility of objectively measured physical activity and sedentary time over
      two seasons in children; Comparing a day-by-day and a week-by-week approach.
AB  - INTRODUCTION: Knowledge of reproducibility of accelerometer-determined physical
      activity (PA) and sedentary time (SED) estimates are a prerequisite to conduct
      high-quality epidemiological studies. Yet, estimates of reproducibility might
      differ depending on the approach used to analyze the data. The aim of the present
      study was to determine the reproducibility of objectively measured PA and SED in
      children by directly comparing a day-by-day and a week-by-week approach to data
      collected over two weeks during two different seasons 3-4 months apart. METHODS:
      676 11-year-old children from the Active Smarter Kids study conducted in Sogn og
      Fjordane county, Norway, performed 7 days of accelerometer monitoring (ActiGraph
      GT3X+) during January-February and April-May 2015. Reproducibility was calculated
      using a day-by-day and a week-by-week approach applying mixed effect modelling
      and the Spearman Brown prophecy formula, and reported using intra-class
      correlation (ICC), Bland Altman plots and 95% limits of agreement (LoA). RESULTS:
      Applying a week-by-week approach, no variables provided ICC estimates >= 0.70 for
      one week of measurement in any model (ICC = 0.29-0.66 not controlling for season;
      ICC = 0.49-0.67 when controlling for season). LoA for these models approximated a
      factor of 1.3-1.7 of the sample PA level standard deviations. Compared to the
      week-by-week approach, the day-by-day approach resulted in too optimistic
      reliability estimates (ICC = 0.62-0.77 not controlling for season; ICC = 0.64
      0.77 when controlling for season). CONCLUSIONS: Reliability is lower when
      analyzed over different seasons and when using a week-by-week approach, than when
      applying a day-by-day approach and the Spearman Brown prophecy formula to
      estimate reliability over a short monitoring period. We suggest a day-by-day
      approach and the Spearman Brown prophecy formula to determine reliability be used
      with caution. TRIAL REGISTRATION: The study is registered in Clinicaltrials.gov
      7th April 2014 with identification number NCT02132494.

PMID- 29216320
TI  - Correction: Fat and Carbohydrate Intake over Three Generations Modify Growth,
      Metabolism and Cardiovascular Phenotype in Female Mice in an Age-Related Manner.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0134664.].

PMID- 29216321
TI  - Correction: Iron deficiency was not the major cause of anemia in rural women of
      reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184742.].

PMID- 29216322
TI  - Correction: Bacterial community and arsenic functional genes diversity in arsenic
      contaminated soils from different geographic locations.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176696.].

PMID- 29216323
TI  - Correction: Formation of homophily in academic performance: Students change their
      friends rather than performance.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183473.].

PMID- 29216324
TI  - Correction: The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills
      of Early Pleistocene hominins in North China.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185101.].

PMID- 29216325
TI  - Correction: The Human Touch: Skin Temperature during the Rubber Hand Illusion in
      Manual and Automated Stroking Procedures.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0080688.].

PMID- 29216326
TI  - Pathogen manipulation of host metabolism: A common strategy for immune evasion.

PMID- 29216327
TI  - Protamine neutralizes chondroitin sulfate proteoglycan-mediated inhibition of
      oligodendrocyte differentiation.
AB  - Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating
      plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair
      remyelination by inhibiting the migration and differentiation of oligodendrocyte
      precursor cells (OPCs) in the central nervous system (CNS). We herein show that
      protamine (PRM, also known as a heparin antagonist) effectively neutralizes the
      inhibitory activities of CSPGs, thereby enhancing OPC differentiation and
      (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells
      revealed that the PRM treatment exerted masking effects on extracellular CSPGs
      and improved oligodendrocyte differentiation on inhibitory CSPG-coated
      substrates. PRM also bound to the extracellular region of protein tyrosine
      phosphatase receptor type Z (PTPRZ), a membrane-spanning CSPG predominantly
      expressed in OPCs, and functioned as a ligand mimetic of PTPRZ, thereby
      suppressing its negative regulatory activity on oligodendrocyte differentiation.
      In primary cultures, the differentiation of OPCs from wild-type and Ptprz
      deficient mice was equally enhanced by PRM. Moreover, the intranasal
      administration of PRM accelerated myelination in the developing mouse brain, and
      its intracerebroventricular administration stimulated remyelination after
      cuprizone-induced demyelination. These results indicate that PRM has CSPG
      neutralizing activity which promotes oligodendrocyte differentiation under
      developmental and morbid conditions.

PMID- 29216328
TI  - Comparative analysis of IDF, ATPIII and CDS in the diagnosis of metabolic
      syndrome among adult inhabitants in Jiangxi Province, China.
AB  - BACKGROUND: Currently, the prevalence of metabolic syndrome (MS) has attracted
      widespread public attention. However, there is a war regarding the applicability
      of the diagnosis in different populations regarding the distinct criteria for the
      diagnosis of MS. Data about the prevalence rate of MS and its components in
      Jiangxi Province are limited. Thus, our goals were to compare the consistency
      rates and applicability of three criteria, i.e., those of the International
      Diabetes Federation (IDF), the National Cholesterol Education Program Adult
      Treatment PanelIII (ATPIII), and the Chinese Diabetes Society (CDS). METHODS:
      From September 2013 to March 2014, 5959 residents (age>=18 years) from Jiangxi
      Province were selected by multistage stratified cluster random sampling methods.
      The prevalence rate of MS and its components were calculated according to the
      IDF, ATPIII and CDS criteria, and the protocols of the different criteria were
      measured in terms of consistency with the kappa statistic and Youden's index.
      Receiver operator characteristic (ROC) curve analysis was used to explore the
      optimal cut-off points of body mass index (BMI) and waist circumference (WC).
      RESULTS: The mean age of the participants was 50.52+/-13.92 years among the total
      of 5959 individuals (2451 male and 3508 female). The standardized prevalence rate
      of MS was 19.85%, 24.77% and 9.95% according to the IDF, ATPIII and CDS criteria,
      respectively. The order of the prevalence rates of the different components of MS
      according to the IDF or ATPIII criteria from high to low were as follows:
      elevated blood pressure, central obesity, reduced high density lipoprotein
      cholesterol (HDL-C), hyperglycemia, and hypertriglyceridemia. The most prevalent
      component of MS, according to the CDS criterion, was being overweight or obese,
      followed by elevated blood pressure, dyslipidemia and hyperglycemia. The Youden's
      index in IDF criterion was higher than which in CDS criterion (0.79 for IDF vs.
      0.38 for CDS) referring to the ATPIII criterion. The agreement between the IDF
      and ATPIII criteria was good (kappa = 0.85), whereas the agreement of the CDS
      with the IDF and ATPIII criteria was moderate (kappa = 0.46 and 0.46,
      respectively). The ability to predict MS risk factors clusters was superior when
      the BMI cut-off point was 24/24kg/m2 (male/female), and the WC cut-off point was
      87/80cm (male/female). Among the 18~59 years old male group, BMI was superior to
      WC in predicting clusters of risk factors for MS; while in the 60 years and above
      male group and all-age female group, WC was superior to BMI. CONCLUSION: Our
      results revealed that the prevalence rate of metabolic syndrome among adults was
      high in Jiangxi Province. BMI and WC had different ability to predict clusters of
      risk factors for MS in different age groups and gender. Among the three criteria
      for MS, there was bigger difference in applicability for the adults of Jiangxi
      Province. The choice of the appropriate criteria should be based on the actual
      conditions of the site.

PMID- 29216329
TI  - Characterization of Fusobacterium varium Fv113-g1 isolated from a patient with
      ulcerative colitis based on complete genome sequence and transcriptome analysis.
AB  - Fusobacterium spp. present in the oral and gut flora is carcinogenic and is
      associated with the risk of pancreatic and colorectal cancers. Fusobacterium spp.
      is also implicated in a broad spectrum of human pathologies, including Crohn's
      disease and ulcerative colitis (UC). Here we report the complete genome sequence
      of Fusobacterium varium Fv113-g1 (genome size, 3.96 Mb) isolated from a patient
      with UC. Comparative genome analyses totally suggested that Fv113-g1 is basically
      assigned as F. varium, in particular, it could be reclassified as notable F.
      varium subsp. similar to F. ulcerans because of partial shared orthologs.
      Compared with the genome sequences of F. varium ATCC 27725 (genome size, 3.30 Mb)
      and other strains of Fusobacterium spp., Fv113-g1 possesses many accessary pan
      genome sequences with noteworthy multiple virulence factors, including 44
      autotransporters (type V secretion system, T5SS) and 13 Fusobacterium adhesion
      (FadA) paralogs involved in potential mucosal inflammation. Indeed, transcriptome
      analysis demonstrated that Fv113-g1-specific accessary genes, such as multiple
      T5SS and fadA paralogs, showed notably increased expression with D-MEM
      cultivation than with brain heart infusion broth. This implied that growth
      condition may enhance the expression of such potential virulence factors, leading
      to remarkable survival against other gut microorganisms and to the pathogenicity
      to human intestinal epithelium.

PMID- 29216331
TI  - Combined short- and long-axis ultrasound-guided central venous catheterization is
      superior to conventional techniques: A cross-over randomized controlled manikin
      trial.
AB  - OBJECTIVES: Visualizing the needle tip using the short-axis (SA) ultrasound
      guided central venous catheterization approach can be challenging. It has been
      suggested to start the process with the SA approach and then switch to the long
      axis (LA); however, to our knowledge, this combination has not been evaluated. We
      compared the combined short- and long-axis (SLA) approach with the SA approach in
      a manikin study. METHODS: We performed a prospective randomized controlled cross
      over study in an urban emergency department and intensive care unit. Resident
      physicians in post-graduate years 1-2 performed a simulated ultrasound-guided
      internal jugular vein puncture using the SA and SLA approaches on manikins.
      Twenty resident physicians were randomly assigned to two equal groups: (1) one
      group performed punctures using the SA approach followed by SLA; and (2) the
      other performed the same procedures in the opposite order. We compared the
      success rate and procedure duration for the two approaches. Procedural success
      was defined as insertion of the guide-wire into the vein while visualizing the
      needle tip at the time of anterior wall puncture, without penetrating the
      posterior wall. RESULTS: Six resident physicians (30%) performed both approaches
      successfully, while 12 (60%) performed the SLA approach, but not the SA,
      successfully. Those who performed the SA approach successfully also succeeded
      with the SLA approach. Two resident physicians (10%) failed to perform both
      approaches. The SLA approach had a significantly higher success rate than the SA
      approach (P < 0.001). The median (interquartile range) procedure duration was
      59.5 [46.0-88.5] seconds and 45.0 [37.5-84.0] seconds for the SLA and SA
      approaches, respectively. The difference of the duration between the two
      procedures was 15.5 [0-28.5] seconds. There was no significant difference in
      duration between the two approaches (P = 0.12). CONCLUSIONS: Using the SLA
      approach significantly improved the success rate of internal jugular vein
      puncture performed by novice physicians on a manikin model, without increasing
      procedural duration. Further clinical trials are warranted to confirm the
      procedure's utility in actual patients. TRIAL REGISTRATION: UMIN Clinical Trials
      Registry UMIN000026199.

PMID- 29216330
TI  - Genome-wide analysis of the Brachypodium distachyon (L.) P. Beauv. Hsp90 gene
      family reveals molecular evolution and expression profiling under drought and
      salt stresses.
AB  - The structure, evolution, and function of heat shock proteins 90 (Hsp90s) have
      been investigated in great detail in fungi and animals. However, studies on the
      Hsp90 genes in plants are generally limited. Brachypodium distachyon (L.) P.
      Beauv., as a model plant for cereal crops, has become a potential biofuel grass.
      During its long evolution, the Hsp90 gene family in Brachypodium has developed
      some strategies to cope with adverse environments. How the Hsp90 gene family in
      Brachypodium evolved in different plant lineages and what its role is in plant
      responses to drought and salt stresses remains to be elucidated. We used a set of
      different bioinformatics tools to identify 94 Hsp90 genes from 10 species
      representing four plant lineages and classified into three subgroups. Eight
      BdHsp90 genes were detected from B. distachyon. The number of exon-intron
      structures differed in each subgroup, and the motif analysis revealed that these
      genes were relatively conservative in each group. The fragments duplication and
      tandem duplication, which are the prime powers for functional diversity,
      generally occurred during the duplication of the whole plant genome.
      Transcriptional analysis of the BdHsp90 genes under salt and drought stress
      conditions indicated that the expression of these genes was delayed or increased
      at different stress time points; The expression was more affected in that of
      Bradi3g39630, Bradi4g06370, and Bradi1g30130. Our findings suggest the
      involvement of BdHsp90s in plant abiotic stress response, and further consolidate
      our views on the stress response mechanism of Hsp90 in general.

PMID- 29216332
TI  - Voltage-dependent calcium channel signaling mediates GABAA receptor-induced
      migratory activation of dendritic cells infected by Toxoplasma gondii.
AB  - The obligate intracellular parasite Toxoplasma gondii exploits cells of the
      immune system to disseminate. Upon T. gondii-infection, gamma-aminobutyric acid
      (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic
      cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that
      calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC
      hypermotility and transmigration in vitro. We report that activation of GABAA
      receptors by GABA induces transient Ca2+ entry in DCs. Murine bone marrow-derived
      DCs preferentially expressed the L-type voltage-dependent Ca2+ channel (VDCC)
      subtype Cav1.3. Silencing of Cav1.3 by short hairpin RNA or selective
      pharmacological antagonism of VDCCs abolished the Toxoplasma-induced
      hypermigratory phenotype. In a mouse model of toxoplasmosis, VDCC inhibition of
      adoptively transferred Toxoplasma-infected DCs delayed the appearance of cell
      associated parasites in the blood circulation and reduced parasite dissemination
      to target organs. The present data establish that T. gondii-induced
      hypermigration of DCs requires signaling via VDCCs and that Ca2+ acts as a second
      messenger to GABAergic signaling via the VDCC Cav1.3. The findings define a novel
      motility-related signaling axis in DCs and unveil that interneurons and DCs share
      common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical
      pathways to induce host cell migration and facilitate dissemination.

PMID- 29216333
TI  - A donor-specific QTL, exhibiting allelic variation for leaf sheath hairiness in a
      nested association mapping population, is located on barley chromosome 4H.
AB  - Leaf sheath hairiness is a morphological trait associated with various
      advantages, including tolerance to both abiotic and biotic stresses, thereby
      increasing yield. Understanding the genetic basis of this trait in barley can
      therefore improve the agronomic performance of this economically important crop.
      We scored leaf sheath hairiness in a two-year field trial in 1,420 BC1S3 lines
      from the wild barley nested association mapping (NAM) population HEB-25. Leaf
      sheath hairiness segregated in six out of 25 families with the reference parent
      Barke being glabrous. We detected the major hairy leaf sheath locus Hs (syn. Hsh)
      on chromosome 4H (111.3 cM) with high precision. The effects of the locus varied
      across the six different wild barley donors, with donor of HEB family 11
      conferring the highest score of leaf sheath hairiness. Due to the high mapping
      resolution present in HEB-25, we were able to discuss physically linked
      pentatricopeptide repeat genes and subtilisin-like proteases as potential
      candidate genes underlying this locus. In this study, we proved that HEB-25
      provides an appropriate tool to further understand the genetic control of leaf
      sheath hairiness in barley. Furthermore, our work represents a perfect starting
      position to clone the gene responsible for the 4H locus observed.

PMID- 29216334
TI  - Orientia tsutsugamushi: A neglected but fascinating obligate intracellular
      bacterial pathogen.

PMID- 29216336
TI  - Managing diabetic kidney disease.
AB  - Introduction: Diabetes mellitus (DM) is the leading cause of chronic kidney
      disease (CKD). This review covers the pillars of care essential for the
      management of diabetic kidney disease (DKD) including (1) early diagnosis, (2)
      improved glycaemic control, (3) treatment of hypertension, (4) identification and
      treatment of associated metabolic bone disease and (5) identification and
      effective management of dyslipidaemia and additional cardiovascular risk factors.
      Sources of data: We searched PubMed for articles using search terms: diabetic
      nephropathy, diabetic kidney disease, diabetes and chronic kidney disease. We
      used clinical guidelines from NICE, the Association of British Clinical
      Diabetologists (ABCD), the Joint British Societies (JBS) and the Kidney Disease:
      Improving Global Outcomes (KDIGO) working group. Areas of agreement: Multiple
      risk factor reduction targeting glycaemic control, blood pressure control,
      dyslipidaemia, smoking and management of obesity is important in preventing and
      in managing DKD. Areas of controversy: Guidelines disagree on the individualized
      glycaemic targets for patients with diabetic kidney disease. Growing points: The
      growing number of patients with DKD is causing increased pressure on limited
      primary care and specialized services. New ways of managing patients using novel
      technology solutions are required. Areas timely for development: The use of novel
      anti-hyperglycaemic agents, particularly sodium glucose co-transporter 2
      inhibitors and GLP-1 receptor agonists, has been associated with a reduction in
      cardiovascular disease and DKD.

PMID- 29216335
TI  - Introgression of Aegilops speltoides segments in Triticum aestivum and the effect
      of the gametocidal genes.
AB  - Background and Aims: Bread wheat (Triticum aestivum) has been through a severe
      genetic bottleneck as a result of its evolution and domestication. It is
      therefore essential that new sources of genetic variation are generated and
      utilized. This study aimed to generate genome-wide introgressed segments from
      Aegilops speltoides. Introgressions generated from this research will be made
      available for phenotypic analysis. Methods: Aegilops speltoides was crossed as
      the male parent to T. aestivum 'Paragon'. The interspecific hybrids were then
      backcrossed to Paragon. Introgressions were detected and characterized using the
      Affymetrix Axiom Array and genomic in situ hybridization (GISH). Key Results:
      Recombination in the gametes of the F1 hybrids was at a level where it was
      possible to generate a genetic linkage map of Ae. speltoides. This was used to
      identify 294 wheat/Ae. speltoides introgressions. Introgressions from all seven
      linkage groups of Ae. speltoides were found, including both large and small
      segments. Comparative analysis showed that overall macro-synteny is conserved
      between Ae. speltoides and T. aestivum, but that Ae. speltoides does not contain
      the 4A/5A/7B translocations present in wheat. Aegilops speltoides has been
      reported to carry gametocidal genes, i.e. genes that ensure their transmission
      through the gametes to the next generation. Transmission rates of the seven Ae.
      speltoides linkage groups introgressed into wheat varied. A 100 % transmission
      rate of linkage group 2 demonstrates the presence of the gametocidal genes on
      this chromosome. Conclusions: A high level of recombination occurs between the
      chromosomes of wheat and Ae. speltoides, leading to the generation of large
      numbers of introgressions with the potential for exploitation in breeding
      programmes. Due to the gametocidal genes, all germplasm developed will always
      contain a segment from Ae. speltoides linkage group 2S, in addition to an
      introgression from any other linkage group.

PMID- 29216337
TI  - BRCA 1 and 2 mutation status: the elephant in the room during oncofertility
      counseling for young breast cancer patients.

PMID- 29216338
TI  - Transcriptome States Reflect Imaging of Aging States.
AB  - In this study, we describe a morphological biomarker that detects multiple
      discrete subpopulations (or "age-states") at several chronological ages in a
      population of nematodes (Caenorhabditis elegans). We determined the frequencies
      of three healthy adult states and the timing of the transitions between them
      across the lifespan. We used short-lived and long-lived strains to confirm the
      general applicability of the state classifier and to monitor state progression.
      This exploration revealed healthy and unhealthy states, the former being favored
      in long-lived strains and the latter showing delayed onset. Short-lived strains
      rapidly transitioned through the putative healthy state. We previously found that
      age-matched animals in different age-states have distinct transcriptome profiles.
      We isolated animals at the beginning and end of each identified state and
      performed microarray analysis (principal component analysis, relative sample to
      sample distance measurements, and gene set enrichment analysis). In some
      comparisons, chronologically identical individuals were farther apart than
      morphologically identical individuals isolated on different days. The age-state
      biomarker allowed assessment of aging in a novel manner, complementary to
      chronological age progression. We found hsp70 and some small heat shock protein
      genes are expressed later in adulthood, consistent with the proteostasis collapse
      model.

PMID- 29216339
TI  - Exercise Training for Preventing Dementia, Mild Cognitive Impairment, and
      Clinically Meaningful Cognitive Decline: A Systematic Review and Meta-analysis.
AB  - Background: To assess the effects of long-term exercise on the onset of dementia,
      mild cognitive impairment (MCI), and other clinically meaningful cognitive
      decline in the elderly adults. Methods: Systematic review with preplanned meta
      analysis. Electronic searches were performed between November 2016 and May 2017.
      Randomized controlled trials (RCTs) examining the effects of long-term exercise
      (intervention length 12 months or longer) on the onset of dementia, MCI, or
      clinically meaningful cognitive decline in older adults without dementia at
      baseline were eligible. Two authors extracted the data independently. Four binary
      outcomes were defined: dementia onset, MCI onset, other clinically meaningful
      cognitive decline, and any of these three outcomes combined. Results: Five
      studies (n = 2,878 participants randomized) were included in this review.
      Outcomes' incidence for exercisers and controls were, respectively: 3.7% (n =
      949) and 6.1% (n = 1,017) for dementia (three studies), 10.2% (n = 686) and 9.1%
      (n = 682) for MCI (one study), 14.5% (n = 124) and 15.4% (n = 123) for other
      clinically meaningful cognitive decline (two studies), and 11.4% (n = 1,073) and
      12.5% (n = 1,140) for all outcomes combined. Meta-analyses found no significant
      effects of exercise for reducing the risk of dementia, MCI, other clinically
      meaningful cognitive decline, or all outcomes combined. Conclusions: Evidence
      from RCTs is limited and does not support that exercise reduces the risk of
      developing clinically important cognitive outcomes. Further long-term exercise
      RCTs are needed before solid conclusions can be drawn.

PMID- 29216342
TI  - Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of
      Salmonella enterica serovars Typhi and Paratyphi.
AB  - Objectives: Surveillance of antimicrobial resistance (AMR) in Salmonella enterica
      serovars Typhi and Paratyphi is essential to provide an evidence base for
      empirical treatment protocols and to monitor emerging AMR. We sought to compare
      phenotypic and WGS-based genotypic methods for the detection of AMR in Salmonella
      Typhi and Salmonella Paratyphi. Methods: WGS data from 603 isolates of Salmonella
      Typhi (n = 332) and Salmonella Paratyphi (n = 271) were mapped to genes or
      chromosomal mutations known to be associated with phenotypic AMR and compared
      with phenotypic susceptibility data interpreted using breakpoints recommended by
      EUCAST. Results: There were two (0.03%) discordant interpretations out of a
      possible 6030 isolate/antimicrobial class combinations. MDR (resistant to three
      or more classes of antimicrobial) was detected in 83/332 (25.0%) Salmonella Typhi
      isolates, but was not detected in Salmonella Paratyphi. Thirty-six (10.8%)
      isolates of Salmonella Typhi were resistant to ciprofloxacin (MIC >0.5 mg/L),
      with 33 (9.9%) of 332 exhibiting mutations in gyrA and parC, and 244 (73.5%)
      isolates had reduced susceptibility to ciprofloxacin (MIC 0.06-0.25 mg/L). In
      comparison, 209/227 (92.1%) isolates of Salmonella Paratyphi A exhibited
      resistance to ciprofloxacin (MIC >0.5 mg/L). No resistance to azithromycin or the
      third-generation cephalosporins was detected. Conclusions: WGS data provided a
      robust and informative approach for monitoring MDR and emerging resistance to
      ciprofloxacin in Salmonella Typhi and Salmonella Paratyphi. Phenotypic
      antimicrobial susceptibility testing continues to be performed to guide targeted
      individual patient treatment, but inferred AMR profiles from WGS data may be used
      for surveillance and to guide empirical therapy.

PMID- 29216340
TI  - Incorporating blood-based liquid biopsy information into cancer staging: time for
      a TNMB system?
AB  - Tissue biopsy is the standard diagnostic procedure for cancer. Biopsy may also
      provide material for genotyping, which can assist in the diagnosis and selection
      of targeted therapies but may fall short in cases of inadequate sampling,
      particularly from highly heterogeneous tumors. Traditional tissue biopsy suffers
      greater limitations in its prognostic capability over the course of disease, most
      obviously as an invasive procedure with potential complications, but also with
      respect to probable tumor clonal evolution and metastasis over time from initial
      biopsy evaluation. Recent work highlights circulating tumor DNA (ctDNA) present
      in the blood as a supplemental, or perhaps an alternative, source of DNA to
      identify the clinically relevant cancer mutational landscape. Indeed, this
      noninvasive approach may facilitate repeated monitoring of disease progression
      and treatment response, serving as a means to guide targeted therapies based on
      detected actionable mutations in patients with advanced or metastatic solid
      tumors. Notably, ctDNA is heralding a revolution in the range of genomic
      profiling and molecular mechanisms to be utilized in the battle against cancer.
      This review will discuss the biology of ctDNA, current methods of detection and
      potential applications of this information in tumor diagnosis, treatment, and
      disease prognosis. Conventional classification of tumors to describe cancer stage
      follow the TNM notation system, heavily weighting local tumor extent (T), lymph
      node invasion (N), and detectable metastasis (M). With recent advancements in
      genomics and bioinformatics, it is conceivable that routine analysis of ctDNA
      from liquid biopsy (B) may make cancer diagnosis, treatment, and prognosis more
      accurate for individual patients. We put forward the futuristic concept of TNMB
      tumor classification, opening a new horizon for precision medicine with the hope
      of creating better outcomes for cancer patients.

PMID- 29216341
TI  - Use and Importance of Nonhuman Primates in Metabolic Disease Research: Current
      State of the Field.
AB  - Obesity and its multiple metabolic sequelae, including type 2 diabetes,
      cardiovascular disease, and fatty liver disease, are becoming increasingly
      widespread in both the developed and developing world. There is an urgent need to
      identify new approaches for the prevention and treatment of these costly and
      prevalent metabolic conditions. Accomplishing this will require the use of
      appropriate animal models for preclinical and translational investigations in
      metabolic disease research. Although studies in rodent models are often useful
      for target/pathway identification and testing hypotheses, there are important
      differences in metabolic physiology between rodents and primates, and
      experimental findings in rodent models have often failed to be successfully
      translated into new, clinically useful therapeutic modalities in humans. Nonhuman
      primates represent a valuable and physiologically relevant model that serve as a
      critical translational bridge between basic studies performed in rodent models
      and clinical studies in humans. The purpose of this review is to evaluate the
      evidence, including a number of specific examples, in support of the use of
      nonhuman primate models in metabolic disease research, as well as some of the
      disadvantages and limitations involved in the use of nonhuman primates. The
      evidence taken as a whole indicates that nonhuman primates are and will remain an
      indispensable resource for evaluating the efficacy and safety of novel
      therapeutic strategies targeting clinically important metabolic diseases,
      including dyslipidemia and atherosclerosis, type 2 diabetes, hepatic steatosis,
      steatohepatitis, and hepatic fibrosis, and potentially the cognitive decline and
      dementia associated with metabolic dysfunction, prior to taking these therapies
      into clinical trials in humans.

PMID- 29216344
TI  - Prostate cancer: updates on current strategies for screening, diagnosis and
      clinical implications of treatment modalities.
AB  - Prostate cancer is the most common cancer in men by way of diagnosis and a
      leading cause of cancer-related deaths. Early detection and intervention remains
      key to its optimum clinical management. This review provides the most updated
      information on the recent methods of prostate cancer screening, imaging and
      treatment modalities. Wherever possible, clinical trial data has been
      supplemented to provide a comprehensive overview of current prostate cancer
      research and development. Considering the recent success of immunotherapy in
      prostate cancer, we discuss cell, DNA and viruses based, as well as combinatorial
      immunotherapeutic strategies in detail. Furthermore, the potential of
      nanotechnology is increasingly being realized, especially in prostate cancer
      research, and we provide an overview of nanotechnology-based strategies, with
      special emphasis on nanotheranostics and multifunctional nanoconstructs.
      Understanding these recent developments is critical to the design of future
      therapeutic strategies to counter prostate cancer.

PMID- 29216345
TI  - Effect of Influenza Vaccination Against Postoperative Pneumonia and Mortality for
      Geriatric Patients Receiving Major Surgery: A Nationwide Matched Study.
AB  - Background: Limited information is available on the association between influenza
      vaccination and postoperative outcomes. Methods: Using Taiwan's National Health
      Insurance Research Database reimbursement claims data from 2008-2013, we
      conducted a matched cohort study of 16903 patients aged >66 years who received
      influenza vaccinations and later underwent major surgery. Using a propensity
      score matching procedure adjusted for sociodemographic characteristics, medical
      condition, surgery type, and anesthesia type, 16903 controls who underwent
      surgery but were not vaccinated were selected. Logistic regressions were used to
      calculate odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative
      pneumonia and in-hospital mortality associated with influenza vaccination.
      Results: Patients who received preoperative influenza vaccination had a lower
      risk of postoperative pneumonia (OR, 0.60; 95% CI, .56-.64) and in-hospital
      mortality (OR, 0.46; 95% CI, .39-.56), compared with unvaccinated patients, in
      both sexes and every age group. Vaccinated patients who underwent surgery also
      had a decreased risk of postoperative intensive care unit admission (OR, 0.56;
      95% CI, .53-.60), shorter hospital stays (P < .0001), and lower medical
      expenditures (P < .0001) than nonvaccinated controls. Conclusions: Vaccinated
      geriatric patients who underwent surgery had lower risks of pneumonia and in
      hospital mortality, compared with unvaccinated patients who underwent similar
      major surgeries. Further studies are needed to explain how preoperative influenza
      vaccination improves perioperative outcomes.

PMID- 29216343
TI  - Nonhuman Primate Models of Respiratory Disease: Past, Present, and Future.
AB  - The respiratory system consists of an integrated network of organs and structures
      that primarily function for gas exchange. In mammals, oxygen and carbon dioxide
      are transmitted through a complex respiratory tract, consisting of the nasal
      passages, pharynx, larynx, and lung. Exposure to ambient air throughout the
      lifespan imposes vulnerability of the respiratory system to environmental
      challenges that can contribute toward development of disease. The importance of
      the respiratory system to human health is supported by statistics from the
      Centers for Disease Control and Prevention; in 2015, chronic lower respiratory
      diseases were the third leading cause of death in the United States. In light of
      the significant mortality associated with respiratory conditions that afflict all
      ages of the human population, this review will focus on basic and preclinical
      research conducted in nonhuman primate models of respiratory disease. In
      comparison with other laboratory animals, the nonhuman primate lung most closely
      resembles the human lung in structure, physiology, and mucosal immune mechanisms.
      Studies defining the influence of inhaled microbes, pollutants, or allergens on
      the nonhuman primate lung have provided insight on disease pathogenesis, with the
      potential for elucidation of molecular targets leading to new treatment
      modalities. Vaccine trials in nonhuman primates have been crucial for
      confirmation of safety and protective efficacy against infectious diseases of the
      lung in a laboratory animal model that recapitulates pathology observed in
      humans. In looking to the future, nonhuman primate models of respiratory diseases
      will continue to be instrumental for translating biomedical research for
      improvement of human health.

PMID- 29216346
TI  - Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected
      individuals with suppressed HIV viraemia.
AB  - Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and
      pharmacological robustness favourably investigated as monotherapy. Whether
      darunavir could be dose reduced in the context of monotherapy deserves
      investigation. Methods: Patients with HIV suppressed viraemia (plasma viral load
      <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir
      monotherapy at 600/100 mg/day between 2013 and 2015 were included in this
      observational 48 week single-centre study. The primary outcome was the proportion
      of patients with virological success (defined as plasma viral load <50 copies/mL)
      at week 24. Secondary outcomes included treatment strategy success and
      resistance. Results: Thirty-one patients were included with the following
      baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3
      (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261)
      and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART
      consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100
      mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)]
      and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up,
      no virological failure occurred and two patients discontinued 600/100 mg of
      darunavir/ritonavir due to side effects at week 16 and 40, leading to a
      virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48.
      Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95%
      CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of
      darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286
      1724) and 1255 ng/mL (873-2161), respectively. Conclusions: A lower dose of
      darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in
      virologically suppressed HIV-infected patients. Further studies are needed to
      confirm these data.

PMID- 29216348
TI  - MIC-based dose adjustment: facts and fables.
AB  - Over recent decades, several publications have described optimization procedures
      for antibiotic therapy in the individual patient based on antimicrobial MIC
      values. Most methods include therapeutic drug monitoring and use a single MIC
      determination plus the relevant pharmacokinetics/pharmacodynamics to adjust the
      dose to optimize antimicrobial drug exposure and antibacterial effects. However,
      the use of an MIC obtained by a single MIC determination is inappropriate. First,
      routine clinical laboratories cannot determine MICs with sufficient accuracy to
      guide dosage owing to the inherent assay variation in the MIC test. Second, the
      variation in any MIC determination, whatever method is used, must be accounted
      for. If dose adjustments are made based on therapeutic drug monitoring and
      include MIC determinations, MIC variation must be considered to prevent potential
      underdosing of patients. We present the problems and some approaches that could
      be used in clinical practice.

PMID- 29216347
TI  - Effect of Staphylococcus aureus Tet38 native efflux pump on in vivo response to
      tetracycline in a murine subcutaneous abscess model.
AB  - Objectives: Staphylococcus aureus native efflux pump Tet38 confers resistance to
      tetracycline when overexpressed. tet38 expression is selectively upregulated in
      infection sites. This study evaluated the effect of Tet38 on tetracycline
      response in a murine subcutaneous abscess model. Methods: S. aureus MW2 and its
      tet38 mutant were injected subcutaneously on the opposite flanks of each mouse.
      The infected mice were treated with tetracycline (10 mg/kg) or PBS (control)
      intraperitoneally every 12 h. The efficacy of tetracycline against S. aureus was
      measured by the relative change in viable bacteria in the abscesses 24 h after
      infection compared with the initial inoculum. Plasmid-based tet38-complemented
      strains were created and used to infect the mice followed by tetracycline or PBS
      treatment. Results: The increased bacterial loads of S. aureus MW2 and its tet38
      mutant in the abscess after 24 h were similar. Tetracycline produced significant
      decreases of both MW2 and the tet38 mutant compared with control. Although the
      tetracycline MICs for MW2 and the tet38 mutant did not differ in vitro, the
      antibacterial effect of tetracycline was significantly 2-fold greater in the
      tet38 mutant compared with the MW2 parental strain in vivo with a decrease of
      0.67 +/- 0.21 and 0.35 +/- 0.19 log10 cfu/abscess, respectively (P < 0.05). The
      increased tetracycline activity in the tet38 mutant was complemented by plasmid
      encoded tet38. Conclusions: This study demonstrated that selective increased
      expression of tet38 in an abscess can affect tetracycline efficacy against S.
      aureus in vivo, highlighting an effect of native efflux pumps on response to
      therapy not reflected by testing in vitro.

PMID- 29216349
TI  - Developing a Standard Set of Patient-Centred Outcomes for Inflammatory Bowel
      Disease-an International, Cross-disciplinary Consensus.
AB  - Background and Aims: Success in delivering value-based healthcare involves
      measuring outcomes that matter most to patients. Our aim was to develop a minimum
      Standard Set of patient-centred outcome measures for inflammatory bowel disease
      [IBD], for use in different healthcare settings. Methods: An international
      working group [n = 25] representing patients, patient associations,
      gastroenterologists, surgeons, specialist nurses, IBD registries and patient
      reported outcome measure [PROM] methodologists participated in a series of
      teleconferences incorporating a modified Delphi process. Systematic review of
      existing literature, registry data, patient focus groups and open review periods
      were used to reach consensus on a minimum set of standard outcome measures and
      risk adjustment variables. Similar methodology has been used in 21 other disease
      areas [www.ichom.org]. Results: A minimum Standard Set of outcomes was developed
      for patients [aged >=16] with IBD. Outcome domains included survival and disease
      control [survival, disease activity/remission, colorectal cancer, anaemia],
      disutility of care [treatment-related complications], healthcare utilization [IBD
      related admissions, emergency room visits] and patient-reported outcomes
      [including quality of life, nutritional status and impact of fistulae] measured
      at baseline and at 6 or 12 month intervals. A single PROM [IBD-Control
      questionnaire] was recommended in the Standard Set and minimum risk adjustment
      data collected at baseline and annually were included: demographics, basic
      clinical information and treatment factors. Conclusions: A Standard Set of
      outcome measures for IBD has been developed based on evidence, patient input and
      specialist consensus. It provides an international template for meaningful,
      comparable and easy-to-interpret measures as a step towards achieving value-based
      healthcare in IBD.

PMID- 29216350
TI  - Italian nationwide survey on Pseudomonas aeruginosa from invasive infections:
      activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of
      carbapenemase producers.
AB  - Objectives: Pseudomonas aeruginosa is a major cause of severe healthcare
      associated infections and often shows MDR phenotypes. Ceftolozane/tazobactam is a
      new cephalosporin/beta-lactamase inhibitor combination with potent activity
      against P. aeruginosa. This survey was carried out to evaluate the susceptibility
      of P. aeruginosa, circulating in Italy, to ceftolozane/tazobactam and comparators
      and to investigate the molecular epidemiology of carbapenemase-producing strains.
      Methods: Consecutive non-replicate P. aeruginosa clinical isolates (935) from
      bloodstream infections and lower respiratory tract infections were collected from
      20 centres distributed across Italy from September 2013 to November 2014.
      Antimicrobial susceptibility testing was performed by broth microdilution and
      results were interpreted according to the EUCAST breakpoints. Isolates resistant
      to ceftolozane/tazobactam were investigated for carbapenemase genes by PCR, and
      for carbapenemase activity by spectrophotometric assay. WGS using an Illumina
      platform was performed on carbapenemase-producing isolates. Results:
      Ceftolozane/tazobactam was the most active molecule, retaining activity against
      90.9% of P. aeruginosa isolates, followed by amikacin (88.0% susceptibility) and
      colistin (84.7% susceptibility). Overall, 48 isolates (5.1%) were positive for
      carbapenemase genes, including blaVIM (n = 32), blaIMP (n = 12) and blaGES-5 (n =
      4), while the remaining ceftolozane/tazobactam-resistant isolates tested negative
      for carbapenemase production. Carbapenemase producers belonged to 10 different
      STs, with ST175 (n = 12) and ST621 (n = 11) being the most common lineages.
      Genome analysis revealed different trajectories of spread for the different
      carbapenemase genes. Conclusions: Ceftolozane/tazobactam exhibited potent in
      vitro activity against P. aeruginosa causing invasive infections in Italy.
      Carbapenemase production was the most common mechanism of resistance to
      ceftolozane/tazobactam.

PMID- 29216351
TI  - beta1-Adrenoceptor in the Central Amygdala Is Required for Unconditioned Stimulus
      Induced Drug Memory Reconsolidation.
AB  - Background: Drug memories become labile and reconsolidated after retrieval by
      presentation of environmental cues (conditioned stimulus) or drugs (unconditioned
      stimulus). Whether conditioned stimulus and unconditioned stimulus retrieval
      trigger different memory reconsolidation processes is not clear. Methods: Protein
      synthesis inhibitor or beta-adrenergic receptor (beta-AR) antagonist was
      systemically administrated or intra-central amygdala infused immediately after
      cocaine reexposure in cocaine-conditioned place preference or self-administration
      mice models. beta-ARs were selectively knocked out in the central amygdala to
      further confirm the role of beta-adrenergic receptor in cocaine reexposure
      induced memory reconsolidation of cocaine-conditioned place preference. Results:
      Cocaine reexposure triggered de novo protein synthesis dependent memory
      reconsolidation of cocaine-conditioned place preference. Cocaine-priming-induced
      reinstatement was also impaired with post cocaine retrieval manipulation, in
      contrast to the relapse behavior with post context retrieval manipulation.
      Cocaine retrieval, but not context retrieval, induced central amygdala
      activation. Protein synthesis inhibitor or beta1-adrenergic receptor antagonist
      infused in the central amygdala after cocaine retrieval, but not context
      retrieval, inhibited memory reconsolidation and reinstatement. beta1-adrenergic
      receptor knockout in the central amygdala suppressed cocaine retrieval-triggered
      memory reconsolidation and reinstatement of cocaine conditioned place preference.
      beta1-adrenergic receptor antagonism after cocaine retrieval also impaired
      reconsolidation and reinstatement of cocaine self-administration. Conclusions:
      Cocaine reward memory triggered by unconditioned stimulus retrieval is distinct
      from conditioned stimulus retrieval. Unconditioned stimulus retrieval induced
      reconsolidation of cocaine reward memory depends on beta1-adrenergic signaling in
      the central amygdala. Post unconditioned stimulus retrieval manipulation can
      prevent drug memory reconsolidation and relapse to cocaine, thus providing a
      potential strategy for the prevention of substance addiction. Significance
      Statement: It is well known that drug memories become labile and reconsolidated
      upon retrieval by the presentation of conditioned stimulus (CS) or unconditioned
      stimulus (US). Whether CS and US retrieval trigger different memory
      reconsolidation processes is unknown. In this study, we found that US retrieval,
      but not CS retrieval, triggered memory reconsolidation of cocaine-conditioned
      place preference dependent on beta1-AR and de novo protein synthesis in the
      central amygdala. Furthermore, cocaine priming-induced reinstatement was impaired
      with post US retrieval manipulation in contrast to the relapse behavior with post
      CS retrieval manipulation. In cocaine self-administration, beta1-AR antagonism
      after US retrieval also impaired reconsolidation and reinstatement. Our study
      indicates that reconsolidation of cocaine reward memory triggered by US retrieval
      is distinct from CS retrieval. US retrieval induced reconsolidation of cocaine
      reward memory depends on beta1-adrenergic signaling in the central amygdala.

PMID- 29216352
TI  - Identification of Estrogen-Related Receptor alpha Agonists in the Tox21 Compound
      Library.
AB  - The estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor (NR)
      that plays a role in energy homeostasis and controls mitochondrial oxidative
      respiration. Increased expression of ERRalpha in certain ovarian, breast, and
      colon cancers has a negative prognosis, indicating an important role for ERRalpha
      in cancer progression. An interaction between ERRalpha and peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) has also
      recently been shown to regulate an enzyme in the beta-oxidation of free fatty
      acids, thereby suggesting that ERRalpha plays an important role in obesity and
      type 2 diabetes. Therefore, it would be prudent to identify compounds that can
      act as activators of ERRalpha. In this study, we screened ~10,000 (8311 unique)
      compounds, known as the Tox21 10K collection, to identify agonists of ERRalpha.
      We performed this screen using two stably transfected HEK 293 cell lines, one
      with the ERRalpha-reporter alone and the other with both ERRalpha-reporter and
      PGC-1alpha expression vectors. After the primary screening, we identified more
      than five agonist clusters based on compound structural similarity analysis
      (e.g., statins). By examining the activities of the confirmed ERRalpha modulators
      in other Tox21 NR assays, eliminating those with promiscuous NR activity, and
      performing follow-up assays (e.g., small interfering RNA knockdown), we
      identified compounds that might act as endocrine disrupters through effects on
      ERRalpha signaling. To our knowledge, this study is the first comprehensive
      analysis in discovering potential endocrine disrupters that affect the ERRalpha
      signaling pathway.

PMID- 29216353
TI  - Effects of Sex Hormone Treatment on the Metabolic Syndrome in Transgender
      Individuals: Focus on Metabolic Cytokines.
AB  - Context: Hormonal treatment in transgender persons affects many components of the
      metabolic syndrome (MS). Objective: To determine the role of direct hormonal
      effects, changes in metabolic cytokines, and body composition on metabolic
      outcomes. Design, Setting, and Participants: 24 transwomen and 45 transmen from
      the European Network for the Investigation of Gender Incongruence were
      investigated at baseline and after 12 months of hormonal therapy. Outcome
      Measures: Best predictors for changes in components of MS, applying least
      absolute shrinkage and selection operator regression. Results: In transwomen, a
      decrease in triglyceride levels was best explained by a decrease in fat mass and
      an increase in fibroblast growth factor 21 (FGF-21); the decrease in total and
      low-density lipoprotein cholesterol levels was principally due to a decrease in
      resistin. A decrease in high-density lipoprotein cholesterol depended on an
      inverse association with fat mass. In contrast, in transmen, an increase in low
      density lipoprotein cholesterol was predicted by a decrease in FGF-21 and an
      increase in the waist/hip ratio; a decrease in the high-density lipoprotein/total
      cholesterol ratio depended on a decline in adiponectin levels. In transwomen,
      worsened insulin resistance and increased early insulin response seemed to be due
      to a direct treatment effect; however, improvements in hepatic insulin
      sensitivity in transmen were best predicted by a positive association with
      chemerin, resistin, and FGF-21 and were inversely related to changes in the
      waist/hip ratio and leptin and adipocyte fatty acid-binding protein levels.
      Conclusions: The effects of hormonal therapy on different components of the MS
      are sex-specific and involve a complex interplay of direct hormonal effects,
      changes in body composition, and metabolic cytokine secretion.

PMID- 29216354
TI  - High Prevalence of Rare Monogenic Forms of Obesity in Obese Guadeloupean Afro
      Caribbean Children.
AB  - Context: The population of Guadeloupe Island exhibits a high prevalence of
      obesity. Objective: We aimed to investigate whether rare genetic mutations in
      genes involved in monogenic obesity (or diabetes) might be causal in this
      population of Afro-Caribbean ancestry. Design and Setting: This was a secondary
      analysis of a study on obesity conducted in schoolchildren from Guadeloupe in
      2013 that aimed to assess changes in children's profiles after a lifestyle
      intervention program. Through next-generation sequencing, we sequenced coding
      regions of 59 genes involved in monogenic obesity or diabetes in participants
      from this study. Participants and Interventions: A total of 25 obese
      schoolchildren from Guadeloupe were screened for rare mutations (nonsynonymous,
      splice-site, or insertion/deletion) in 59 genes. Main Outcome Measures:
      Correlation between phenotypes and mutations of interest. Results: We detected
      five rare heterozygous mutations in five different children with obesity: MC4R
      p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1
      p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2
      p.Leu140Phe that was of uncertain significance. In parallel, we identified seven
      carriers of mutations in ABCC8 (p.Lys1521Asn and p.Ala625Val) or KCNJ11
      (p.Val13Met and p.Val151Met) that were of uncertain significance. Conclusions: We
      were able to detect pathogenic or likely pathogenic mutations linked to severe
      obesity in >15% of this population, which is much higher than what we observed in
      Europeans (~5%).

PMID- 29216355
TI  - Prevalence of and Risk Factors for Anal Human Papillomavirus Infection in a
      Sample of Young, Predominantly Black Men Who Have Sex With Men, Houston, Texas.
AB  - Background: Young men who have sex with men (MSM) are at increased risk for human
      papillomavirus (HPV)-associated disease as a result of HPV infection. Our
      objective was to characterize the prevalence of high-risk anal HPV infection and
      factors associated with prevalence in a group of young, primarily black MSM in
      Houston, Texas. Methods: MSM aged 18-29 years were recruited using a respondent
      driven sampling method to study HIV and sexually transmitted disease transmission
      and risk. All engaged in peer-recruitment chains and self-collected anal
      exfoliated cells. Prevalence ratios assessed factors associated with high-risk
      HPV and HPV types in the 9-valent vaccine. Results: Black race was reported by
      87% of men. Slightly over one half (53%) were human immunodeficiency virus (HIV)
      positive. Approximately 75% of men had at least 1 high-risk HPV type, and 39% of
      HIV-positive men harbored HPV-16. Analysis that controlled for potential
      confounders revealed that only HIV infection was associated with high-risk HPV
      infection. Conclusion: Black MSM would benefit from increased HPV vaccination
      efforts, owing to high rates of HPV infection, increased HPV disease, and low
      vaccination series completion rates in this population.

PMID- 29216356
TI  - Improved EGFR mutation detection using combined exosomal RNA and circulating
      tumor DNA in NSCLC patient plasma.
AB  - Background: A major limitation of circulating tumor DNA (ctDNA) for somatic
      mutation detection has been the low level of ctDNA found in a subset of cancer
      patients. We investigated whether using a combined isolation of exosomal RNA
      (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for
      EGFR mutation detection in non-small-cell lung cancer (NSCLC) patients. Patients
      and methods: Matched pretreatment tumor and plasma were collected from 84
      patients enrolled in TIGER-X (NCT01526928), a phase 1/2 study of rociletinib in
      mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA) was
      analyzed blinded for mutations using a targeted next-generation sequencing panel
      (EXO1000) and compared with existing data from the same samples using analysis of
      ctDNA by BEAMing. Results: For exoNA, the sensitivity was 98% for detection of
      activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities
      for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M. In a
      subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the
      sensitivity increased from 26% to 74% for activating mutations (P = 0.003) and
      from 19% to 31% for T790M (P = 0.5) when using exoNA for detection. Conclusions:
      Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection
      in plasma, with the largest improvement seen in the subgroup of M0/M1a disease
      patients known to have low levels of ctDNA and poses challenges for mutation
      detection on ctDNA alone. Clinical Trials: NCT01526928.

PMID- 29216357
TI  - Parental History of Type 2 Diabetes Abrogates Ethnic Disparities in Key
      Glucoregulatory Indices.
AB  - Context: There are ethnic differences in glucoregulation and prevalence of type 2
      diabetes, but studies on the role of genetics in modifying ethnic effects in
      normoglycemic African-Americans and Caucasians are limited. Therefore, we
      investigated glucoregulation in normoglycemic African-Americans and Caucasians
      with or without parental diabetes. Design: Fifty subjects with parental diabetes
      (from the Pathobiology of Prediabetes in a Biracial Cohort Study) and 50 subjects
      without parental diabetes were matched in age, sex, ethnicity, and body mass
      index (BMI). Subjects underwent a 75-g oral glucose tolerance test (OGTT),
      physical examination, anthropometry, biochemistries, indirect calorimetry and
      assessment of body composition, insulin sensitivity by euglycemic clamp (Si
      clamp), and beta-cell function by Disposition index. Results: The mean age was
      40.5 +/- 11.6 years, BMI 28.7 +/- 5.9 kg/m2, fasting plasma glucose 90.2 +/- 5.9
      mg/dL, and 2-hour postglucose 120.0 +/- 26.8 mg/dL. Offspring with parental
      diabetes showed higher glycemic excursion during OGTT-area under the curve
      glucose (16,005.6 +/- 2324.7 vs 14,973.8 +/- 1819.9, P < 0.005), lower Si-clamp
      (0.132 +/- 0.068 vs 0.162 +/- 0.081 umol/kg fat-free mass/min/pmol/L, P < 0.05),
      and lower Disposition index (8.74 +/- 5.72 vs 11.83 +/- 7.49, P < 0.05). Compared
      with lean subjects without parental diabetes, beta cell function was lower by
      ~30% in lean subjects with parental diabetes, ~40% in obese subjects without
      parental diabetes, and ~50% in obese individuals with parental diabetes (P <
      0.0001). African-Americans without parental diabetes had ~40% lower insulin
      sensitivity (P < 0.001), twofold higher acute insulin secretion (P < 0.001), but
      ~30% lower Disposition index (P < 0.01) compared with Caucasians without parental
      diabetes. Remarkably, there were no significant differences by ethnicity in these
      glucoregulatory measures among subjects with parental diabetes. Conclusion:
      Offspring with parental diabetes harbor substantial impairments in
      glucoregulation compared with individuals without parental diabetes. Ethnic
      disparities in glucoregulation were abrogated by parental diabetes.

PMID- 29216358
TI  - Rapid Protective Effects of Early BCG on Neonatal Mortality Among Low Birth
      Weight Boys: Observations From Randomized Trials.
AB  - Background: Three randomized trials (RCTs) in low-weight (<2.5 kg) infants have
      shown that Bacille Calmette-Guerin (BCG) vaccine nonspecifically reduces all
      cause mortality in the neonatal period. Methods: Using data from 3 RCTs of early
      BCG (n = 6583) we examined potential sex differences in the timing of the
      mortality reduction in the neonatal period, presenting metaestimates of the main
      outcome mortality rate ratios (MRR) for BCG-vaccinated and controls. Results:
      Among controls, boys had a particularly high mortality during the first week
      after randomization: male-female MRR 2.71 (95% CI, 1.70-4.50). During the first
      week, BCG had a marked beneficial effect for boys, reducing mortality 3-fold (MRR
      [BCG/no BCG] = 0.36 [0.20-0.67]). In weeks 2-4 the effect waned for boys (MRR =
      0.91 [0.51-1.69]). In girls, the pattern was opposite with a limited effect in
      the first week (MRR = 0.85 [0.46-1.54]), but a significant reduction in weeks 2-4
      (MRR = 0.56 [0.31-1.00]). This was consistent in all 3 trials. Verbal autopsies
      linked early benefit to fewer sepsis-related deaths among BCG-vaccinated boys.
      Discussion: The marked reduction in mortality in the days after BCG vaccination
      in boys emphasizes the importance of providing BCG soon after birth. Trial
      registration numbers: ClinicalTrials.gov (NCT00146302) and ClinicalTrials.gov
      (NCT00625482).

PMID- 29216359
TI  - Fungaemia caused by rare yeasts: incidence, clinical characteristics and outcome
      over 10 years.

PMID- 29216360
TI  - Comprehensive Genome-Wide Classification Reveals That Many Plant-Specific
      Transcription Factors Evolved in Streptophyte Algae.
AB  - Plant genomes encode many lineage-specific, unique transcription factors.
      Expansion of such gene families has been previously found to coincide with the
      evolution of morphological complexity, although comparative analyses have been
      hampered by severe sampling bias. Here, we make use of the recently increased
      availability of plant genomes. We have updated and expanded previous rule sets
      for domain-based classification of transcription associated proteins (TAPs),
      comprising transcription factors and transcriptional regulators. The genome-wide
      annotation of these protein families has been analyzed and made available via the
      novel TAPscan web interface. We find that many TAP families previously thought to
      be specific for land plants actually evolved in streptophyte (charophyte) algae;
      26 out of 36 TAP family gains are inferred to have occurred in the common
      ancestor of the Streptophyta (uniting the land plants-Embryophyta-with their
      closest algal relatives). In contrast, expansions of TAP families were found to
      occur throughout streptophyte evolution. 17 out of 76 expansion events were found
      to be common to all land plants and thus probably evolved concomitant with the
      water-to-land-transition.

PMID- 29216361
TI  - Gonadotropin-Releasing Hormone Receptor Antagonist Mono- and Combination Therapy
      With Estradiol/Norethindrone Acetate Add-Back: Pharmacodynamics and Safety of
      OBE2109.
AB  - Context: OBE2109 is a potent, oral gonadotropin-releasing hormone receptor
      antagonist being developed for the treatment of sex-hormone-dependent diseases in
      women. Objective: We assessed the pharmacodynamics and safety of OBE2109 alone
      and combined with estradiol (E2)/norethindrone acetate (NETA) add-back therapy on
      E2 levels and vaginal bleeding. Design, Setting, and Participants: This was a
      single-center, open-label, randomized, parallel-group study in 76 healthy
      premenopausal women. Interventions: Women were randomly assigned to take the
      following doses (in milligrams) once daily for 6 weeks: OBE2109, 100 or 200; or
      OBE2109/E2/NETA, 100/0.5/0.1, or 100/1.0/0.5, or 200/1.0/0.5. Main Outcome
      Measures: E2 concentrations, bleeding pattern, exploratory bone metabolism
      biomarkers, and adverse events. Results: OBE2109 100 mg and 200 mg alone reduced
      E2 levels to reach median levels of 19.5 and 3.2 pg/mL, respectively, at week 4.
      Median E2 levels after combined OBE2109/add-back therapy ranged between 25 and 40
      pg/mL. OBE2109 100 mg or 200 mg alone induced amenorrhea. By day 15, >85% of
      women had no vaginal bleeding during the last 4 weeks of treatment. Add-back
      therapy partially impaired bleeding control: The highest amenorrhea rate (53%)
      was observed with OBE2109 100 mg/1.0 mg/0.5 mg. The addition of E2/NETA,
      particularly at 1 mg/0.5 mg, mitigated the increase of two bone markers induced
      by OBE2109 200 mg. Conclusion: OBE2109 promptly lowered E2 levels. Add-back
      therapy may be required to prevent adverse effects on bone in women treated with
      the 200-mg dose (at 100 mg in some women). These results provide a basis for
      OBE2109 regimen selection to treat sex-hormone-dependent diseases.

PMID- 29216362
TI  - A Herpes Simplex Virus (HSV)-2 Single-Cycle Candidate Vaccine Deleted in
      Glycoprotein D Protects Male Mice From Lethal Skin Challenge With Clinical
      Isolates of HSV-1 and HSV-2.
AB  - Herpes simplex virus (HSV) infections manifest as recurrent oral or genital
      mucosal lesions, meningoencephalitis, corneal blindness, and perinatal disease.
      Subunit vaccines have advanced into the clinic without success. None were tested
      preclinically in male mice. We compared a single-cycle candidate vaccine deleted
      in HSV-2 glycoprotein D (DeltagD-2) and subunit gD-2 or gD-1 protein vaccines in
      a male murine skin model. The DeltagD-2 provided complete protection against 10
      times the lethal dose of HSV-1 or HSV-2 clinical isolates, and no latent virus
      was detected, whereas gD-1- and gD-2-adjuvanted proteins provided little or no
      protection. Protection correlated with Fc receptor activating but not
      neutralizing antibody titers.

PMID- 29216364
TI  - Energetic funnel facilitates facilitated diffusion.
AB  - Transcription factors (TFs) are able to associate to their binding sites on DNA
      faster than the physical limit posed by diffusion. Such high association rates
      can be achieved by alternating between three-dimensional diffusion and one
      dimensional sliding along the DNA chain, a mechanism-dubbed facilitated
      diffusion. By studying a collection of TF binding sites of Escherichia coli from
      the RegulonDB database and of Bacillus subtilis from DBTBS, we reveal a funnel in
      the binding energy landscape around the target sequences. We show that such a
      funnel is linked to the presence of gradients of AT in the base composition of
      the DNA region around the binding sites. An extensive computational study of the
      stochastic sliding process along the energetic landscapes obtained from the
      database shows that the funnel can significantly enhance the probability of TFs
      to find their target sequences when sliding in their proximity. We demonstrate
      that this enhancement leads to a speed-up of the association process.

PMID- 29216363
TI  - Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis
      Express Increased Inflammatory Responses After Antimony Therapy.
AB  - Background: Early cutaneous leishmaniasis (ECL) is characterized by a
      nonulcerated papular lesion and illness duration less than 30 days. Approximately
      4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised
      to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We
      hypothesize that the inflammatory response in ECL patients may increase during
      Sb5 therapy, which leads to treatment failure. Methods: A cohort of 44 ECL
      patients infected by Leishmania braziliensis was established to evaluate the
      response to Sb5 and to compare immunologic responses in ECL patients with CL and
      healthy subjects. Results: A hierarchical clustering based on cytokine levels
      showed a weak positive correlation between proinflammatory cytokine levels and
      those patients that failed Sb5 treatment. Although Sb5 therapy decreased
      interferon-gamma and tumor necrosis factor levels in CL patients, we were
      surprised to find that an increase in these cytokines was observed in ECL
      patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune
      responses in ECL. Conclusions: The enhanced production of proinflammatory
      cytokines, due in part to the decreased ability of IL-10 to down-modulate immune
      response during therapy in ECL, promotes the development and persistence of
      leishmania ulcer despite antimony therapy.

PMID- 29216366
TI  - LncRNA lnc-RI regulates homologous recombination repair of DNA double-strand
      breaks by stabilizing RAD51 mRNA as a competitive endogenous RNA.
AB  - DNA double-strand break (DSB) repair is critical for the maintenance of genome
      stability. The current models of the mechanism of DSB repair are based on studies
      of DNA repair proteins. Long non-coding RNAs (lncRNAs) have recently emerged as
      new regulatory molecules, with diverse functions in biological processes. In the
      present study, we found that expression of the ionizing radiation-inducible
      lncRNA, lnc-RI, was correlate negatively with micronucleus frequencies in human
      peripheral blood lymphocytes. Knockdown of lnc-RI significantly increased
      spontaneous DSBs levels, which was confirmed to be associated with the decreased
      efficiency of homologous recombination (HR) repair of DSBs. The expression of
      RAD51, a key recombinase in the HR pathway, decreased sharply in lnc-RI-depressed
      cells. In a further investigation, we demonstrated that miR-193a-3p could bind
      with both lnc-RI and RAD51 mRNA and depressed the expression of lnc-RI and RAD51
      mRNA. Lnc-RI acted as a competitive endogenous RNA (ceRNA) to stabilize RAD51
      mRNA via competitive binding with miR-193a-3p and release of its inhibition of
      RAD51 expression. To our knowledge, this is the first study to demonstrate the
      role of lnc-RI in regulating HR repair of DSBs. The feedback loop established in
      the current study suggests that lnc-RI is critical for the maintenance of genomic
      stability.

PMID- 29216367
TI  - Age and Sex in the Zika Pandemic Era.

PMID- 29216368
TI  - Ross River Virus and the Necessity of Multiscale, Eco-epidemiological Analyses.
AB  - Background: Zoonotic vector-borne disease prevalence is affected by vector,
      human, and reservoir host factors, which are influenced by habitat and climate;
      these 5 components interact on microhabitat-to-landscape scales but are often
      analyzed at a single spatial scale. Methods: We present an information theoretic,
      multiscale, multiple regression analysis of the ecological drivers of Ross River
      virus. We analyze the spatial pattern of 20 years of Ross River virus infections
      from South Australia (1992-2012; n = 5261), using variables across these 5
      components of disease ecology at 3 spatial scales. Results: We found that
      covariate importance depended on the spatial scale of the analysis; some biotic
      variables were more important at fine scales and some abiotic variables were more
      important at coarser spatial scales. The urban score of an area was most
      predictive of infections, and mosquito variables did not improve the explanatory
      power of these models. Conclusions: Through this multiscale analysis, we
      identified novel drivers of the spatial distribution of disease and recommend
      public health interventions. Our results underline that single-scale analyses may
      paint an incomplete picture of disease drivers, potentially creating a major flaw
      in epidemiological analyses. Multiscale, ecological analyses are needed to better
      understand infectious disease transmission.

PMID- 29216365
TI  - Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.
AB  - Tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are eukaryotic enzymes that
      clean-up after aberrant topoisomerase activity. While TDP1 hydrolyzes
      phosphotyrosyl peptides emanating from trapped topoisomerase I (Top I) from the
      3' DNA ends, topoisomerase 2 (Top II)-induced 5'-phosphotyrosyl residues are
      processed by TDP2. Even though the canonical functions of TDP1 and TDP2 are
      complementary, they exhibit little structural or sequence similarity. Homozygous
      mutations in genes encoding these enzymes lead to the development of severe
      neurodegenerative conditions due to the accumulation of transcription-dependent
      topoisomerase cleavage complexes underscoring the biological significance of
      these enzymes in the repair of topoisomerase-DNA lesions in the nervous system.
      TDP1 can promiscuously process several blocked 3' ends generated by DNA damaging
      agents and nucleoside analogs in addition to hydrolyzing 3'-phosphotyrosyl
      residues. In addition, deficiency of these enzymes causes hypersensitivity to
      anti-tumor topoisomerase poisons. Thus, TDP1 and TDP2 are promising therapeutic
      targets and their inhibitors are expected to significantly synergize the effects
      of current anti-tumor therapies including topoisomerase poisons and other DNA
      damaging agents. This review covers the structural aspects, biology and
      regulation of these enzymes, along with ongoing developments in the process of
      discovering safe and effective TDP inhibitors.

PMID- 29216369
TI  - The Pentatricopeptide Repeat Protein MEF31 is Required for Editing at Site 581 of
      the Mitochondrial tatC Transcript and Indirectly Influences Editing at Site 586
      of the Same Transcript.
AB  - Pentatricopeptide repeat (PPR) proteins constitute the largest family of proteins
      in angiosperms, and most members are predicted to play roles in the maturation of
      organellar RNAs. Here we describe the novel mitochondrial editing factor 31
      (MEF31), an E-PPR protein involved in editing at two close sites in the same
      transcript encoding subunit C of the twin-arginine translocation (tat) pathway.
      MEF31 is essential for editing at site tatC-581 and application of the recently
      proposed amino acid code for RNA recognition by PPR proteins supports the view
      that MEF31 directly targets this site by recognizing its cis sequence. In
      contrast, editing at site tatC-586 five nucleotides downstream is only partially
      affected in plants lacking MEF31, being restored to wild-type levels in
      complemented plants. Application of the amino acid code and analysis of
      individual RNA molecules for editing at sites 581 and 586 suggest that MEF31 does
      not directly target site tatC-586, and only indirectly influences editing at this
      site. It is likely that editing at site tatC-581 improves recognition of the site
      tatC-586 cis sequence by a second unknown PPR protein.

PMID- 29216370
TI  - The Role of Arabidopsis Inositol Polyphosphate Kinase AtIPK2beta in Glucose
      Suppression of Seed Germination and Seedling Development.
AB  - Seed germination and subsequent seedling development are critical phases in
      plants. These processes are regulated by a complex molecular network in which
      sugar has been reported to play an essential role. However, factors affecting
      sugar responses remain to be fully elucidated. In this study, we demonstrate that
      AtIPK2beta, known to participate in the synthesis of myo-inositol 1,2,3,4,5,6
      hexakisphosphate (IP6, phytate), affects Arabidopsis responses to glucose during
      seed germination. The loss-of-function mutant atipk2beta showed increased
      sensitivity to 6% glucose and paclobutrazol (PAC). Yeast two-hybrid assay showed
      that AtIPK2beta interacts with sucrose non-fermenting-1-related protein kinase
      (SnRK1.1), and bimolecular fluorescence complementation (BiFC) and pull-down
      assay further confirmed this interaction. Moreover, AtIPK2beta was phosphorylated
      by SnRK1.1 in vitro, and the effect of restoring AtIPK2beta to yeast cells
      lacking IPK2 (Deltaipk2) was abolished by catalytically active SnRK1.1. Further
      analysis indicated that IP6 reduces the suppression of seed germination caused by
      glucose, accompanied by altered expression levels of glucose-/hormone-responsive
      genes. Collectively, these findings indicate that AtIPK2beta and IP6 are involved
      in glucose suppression of seed germination and that AtIPK2beta enzyme activity is
      likely to be regulated by SnRK1.1.

PMID- 29216371
TI  - Fission yeast Ccq1 is a modulator of telomerase activity.
AB  - Shelterin, the telomeric protein complex, plays a crucial role in telomere
      homeostasis. In fission yeast, telomerase is recruited to chromosome ends by the
      shelterin component Tpz1 and its binding partner Ccq1, where telomerase binds to
      the 3' overhang to add telomeric repeats. Recruitment is initiated by the
      interaction of Ccq1 with the telomerase subunit Est1. However, how telomerase is
      released following elongation remains to be established. Here, we show that Ccq1
      also has a role in the suppression of telomere elongation, when coupled with the
      Clr4 histone H3 methyl-transferase complex and the Clr3 histone deacetylase and
      nucleosome remodelling complex, SHREC. We have dissected the functions of Ccq1 by
      establishing a Ccq1-Est1 fusion system, which bypasses the telomerase recruitment
      step. We demonstrate that Ccq1 forms two distinct complexes for positive and
      negative telomerase regulation, with Est1 and Clr3 respectively. The negative
      form of Ccq1 promotes dissociation of Ccq1-telomerase from Tpz1, thereby
      restricting local telomerase activity. The Clr4 complex also has a negative
      regulation activity with Ccq1, independently of SHREC. Thus, we propose a model
      in which Ccq1-Est1 recruits telomerase to mediate telomere extension, whilst
      elongated telomeric DNA recruits Ccq1 with the chromatin-remodelling complexes,
      which in turn releases telomerase from the telomere.

PMID- 29216372
TI  - The C-terminal domain of p53 orchestrates the interplay between non-covalent and
      covalent poly(ADP-ribosyl)ation of p53 by PARP1.
AB  - The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key
      roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose)
      binding and covalent PARylation control protein functions, however, it is unknown
      how the two modes of modification crosstalk mechanistically. Employing the tumor
      suppressor p53 as a model substrate, this study provides detailed insights into
      the interplay between non-covalent and covalent PARylation and unravels its
      functional significance in the regulation of p53. We reveal that the
      multifunctional C-terminal domain (CTD) of p53 acts as the central hub in the
      PARylation-dependent regulation of p53. Specifically, p53 bound to auto-PARylated
      PARP1 via highly specific non-covalent PAR-CTD interaction, which conveyed target
      specificity for its covalent PARylation by PARP1. Strikingly, fusing the p53-CTD
      to a protein that is normally not PARylated, renders this a target for covalent
      PARylation as well. Functional studies revealed that the p53-PAR interaction had
      substantial implications on molecular and cellular levels. Thus, PAR
      significantly influenced the complex p53-DNA binding properties and controlled
      p53 functions, with major implications on the p53-dependent interactome,
      transcription, and replication-associated recombination. Remarkably, this
      mechanism potentially also applies to other PARylation targets, since a
      bioinformatics analysis revealed that CTD-like regions are highly enriched in the
      PARylated proteome.

PMID- 29216374
TI  - Staphylococcus aureus and Pseudomonas aeruginosa Respiratory Tract Coinfection
      What Can We Learn From Animal Models?

PMID- 29216373
TI  - Protective Effect of Maternal Influenza Vaccination on Influenza in Their
      Infants: A Prospective Cohort Study.
AB  - Background: Infants <6 months of age are too young to receive influenza vaccine,
      despite being at high risk for severe influenza-related complications. Methods:
      To examine the effectiveness of maternal influenza vaccination in preventing
      influenza in their infants, we conducted a prospective cohort study of 3441
      infants born at participating hospitals before the 2013-2014 influenza season. At
      the time of recruitment, their mothers completed a questionnaire about influenza
      vaccination status for the 2013-2014 season. A follow-up survey was conducted
      after the end of the 2013-2014 season to collect information regarding influenza
      diagnosis and hospitalization among infants. Results: During the 2013-2014
      influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%)
      were hospitalized with influenza. Maternal influenza vaccination (especially
      prenatal vaccination) decreased the odds of influenza among infants. The
      effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%),
      whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal
      influenza vaccination was also associated with a decreased odds of influenza
      related hospitalization among infants, vaccine effectiveness (73%) did not reach
      statistical significance, owing to the limited number of infants hospitalized
      because of influenza. Conclusions: The present findings indicated that pregnant
      women and postpartum women should receive influenza vaccination to protect their
      infants.

PMID- 29216375
TI  - Binary control of enzymatic cleavage of DNA origami by structural
      antideterminants.
AB  - Controlling DNA nanostructure interaction with protein is essential in developing
      nanodevices with programmable function, reactivity, and stability for biological
      and medical applications. Here, we show that the sequence-specific action of
      restriction endonucleases towards sharp triangular or rectangular DNA origami
      exhibits a novel, binary 'on/off' behaviour, as canonical recognition sites are
      either essentially fully reactive, or strongly resistant to enzymatic cutting.
      Moreover, introduction of structural defects in the sharp triangle can activate
      an otherwise unreactive site, with a site-to-defect distance of ~50 nm. We argue
      that site reactivity is dependent upon programmable, mechanical coupling in the
      two-dimensional DNA origami, with specific structural elements, including DNA
      nicks and branches proximal to the sites that can function as negative(anti)
      determinants of reactivity. Empirically modelling the constraints to DNA degrees
      of freedom associated with each recognition site in the sharp triangle can
      rationalize the pattern of suppressed reactivity towards nine restriction
      endonucleases, in substantial agreement with the experimental results. These
      results provide a basis for a predictive understanding of structure-reactivity
      correlates of specific DNA nanostructures, which will allow a better
      understanding of the behaviour of nucleic acids under nanoscale confinement, as
      well as in the rational design of functional nanodevices based on self-assembling
      nucleic acids.

PMID- 29216376
TI  - Differences in Prevalence of Symptomatic Zika Virus Infection, by Age and Sex
      Puerto Rico, 2016.
AB  - Background: During the outbreak of Zika virus (ZIKV) disease in Puerto Rico in
      2016, nonpregnant women aged 20-39 years were disproportionately identified with
      ZIKV disease. We used household-based cluster investigations to determine whether
      this disparity was associated with age- or sex-dependent differences in the rate
      of ZIKV infection or reported symptoms. Methods: Participation was offered to
      residents of households within a 100-m radius of the residences of a convenience
      sample of 19 laboratory-confirmed ZIKV disease cases. Participants answered a
      questionnaire and provided specimens for diagnostic testing by reverse
      transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA). Results: Among 367 study participants, 114 (31.1%) were laboratory
      positive for ZIKV infection, of whom 30% reported a recent illness (defined as
      self-reported rash or arthralgia) attributable to ZIKV infection. Age and sex
      were not associated with ZIKV infection. Female sex (adjusted prevalence ratio
      [aPR], 2.28; 95% confidence interval [CI], 1.40, 3.67), age <40 years (aPR, 2.39;
      95% CI, 1.55, 3.70), and asthma (aPR, 1.63; 95% CI, 1.12, 2.37) were
      independently associated with symptomatic infection. Conclusions: Although
      neither female sex nor age were associated with an increased prevalence of ZIKV
      infection, both were associated with symptomatic infection. Further investigation
      to identify a potential mechanism of age- and sex-dependent differences in
      reporting symptomatic ZIKV infection is warranted.

PMID- 29216377
TI  - PeachVar-DB: A Curated Collection of Genetic Variations for the Interactive
      Analysis of Peach Genome Data.
AB  - Applying next-generation sequencing (NGS) technologies to species of agricultural
      interest has the potential to accelerate the understanding and exploration of
      genetic resources. The storage, availability and maintenance of huge quantities
      of NGS-generated data remains a major challenge. The PeachVar-DB portal,
      available at http://hpc-bioinformatics.cineca.it/peach, is an open-source catalog
      of genetic variants present in peach (Prunus persica L. Batsch) and wild-related
      species of Prunus genera, annotated from 146 samples publicly released on the
      Sequence Read Archive (SRA). We designed a user-friendly web-based interface of
      the database, providing search tools to retrieve single nucleotide polymorphism
      (SNP) and InDel variants, along with useful statistics and information. PeachVar
      DB results are linked to the Genome Database for Rosaceae (GDR) and the Phytozome
      database to allow easy access to other external useful plant-oriented resources.
      In order to extend the genetic diversity covered by the PeachVar-DB further, and
      to allow increasingly powerful comparative analysis, we will progressively
      integrate newly released data.

PMID- 29216378
TI  - Melonet-DB, a Grand RNA-Seq Gene Expression Atlas in Melon (Cucumis melo L.).
AB  - Melon (Cucumis melo L.) is an important Cucurbitaceae crop produced worldwide,
      exhibiting wide genetic variations and comprising both climacteric and non
      climacteric fruit types. The muskmelon cultivar "'Earl's favorite Harukei-3
      (Harukei-3)"' known for its sweetness and rich aroma is used for breeding of high
      grade muskmelon in Japan. We conducted RNA sequencing (RNA-seq) transcriptome
      studies in 30 different tissues of the 'Harukei-3' melon. These included root,
      stems, leaves, flowers, regenerating callus and ovaries, in addition to the flesh
      and peel sampled at seven stages of fruit development. The expression patterns of
      20,752 genes were determined with fragments per kilobase of transcript per
      million fragments sequenced (FPKM) >1 in at least one tissue. Principal component
      analysis distinguished 30 melon tissues based on the global gene expression
      profile and, further, the weighted gene correlation network analysis classified
      melon genes into 45 distinct coexpression groups. Some coexpression groups
      exhibited tissue-specific gene expression. Furthermore, we developed and
      published web application tools designated "'Gene expression map viewer"' and
      "'Coexpression viewer"' on our website Melonet-DB (http://melonet
      db.agbi.tsukuba.ac.jp/) to promote functional genomics research in melon. By
      using both tools, we analyzed melon homologs of tomato fruit ripening regulators
      such as E8, RIPENING-INHIBITOR (RIN) and NON-RIPENING (NOR). The "'Coexpression
      viewer"' clearly distinguished fruit ripening-associated melon RIN/NOR/CNR
      homologs from those expressed in other tissues. In addition, several other MADS
      box, NAM/ATAF/CUC (NAC) and homeobox transcription factor genes were identified
      as fruit ripening-associated genes. Our tools provide useful information for
      research not only on melon but also on other fleshy fruit plants.

PMID- 29216379
TI  - Endothelial cell differentiation is encompassed by changes in long range
      interactions between inactive chromatin regions.
AB  - Endothelial cells (ECs) differentiate from mesodermal progenitors during
      vasculogenesis. By comparing changes in chromatin interactions between human
      umbilical vein ECs, embryonic stem cells and mesendoderm cells, we identified
      regions exhibiting EC-specific compartmentalization and changes in the degree of
      connectivity within topologically associated domains (TADs). These regions were
      characterized by EC-specific transcription, binding of lineage-determining
      transcription factors and cohesin. In addition, we identified 1200 EC-specific
      long-range interactions (LRIs) between TADs. Most of the LRIs were connected
      between regions enriched for H3K9me3 involving pericentromeric regions,
      suggesting their involvement in establishing compartmentalization of
      heterochromatin during differentiation. Second, we provide evidence that EC
      specific LRIs correlate with changes in the hierarchy of chromatin aggregation.
      Despite these rearrangements, the majority of chromatin domains fall within a pre
      established hierarchy conserved throughout differentiation. Finally, we
      investigated the effect of hypoxia on chromatin organization. Although hypoxia
      altered the expression of hundreds of genes, minimal effect on chromatin
      organization was seen. Nevertheless, 70% of hypoxia-inducible genes situated
      within a TAD bound by HIF1alpha suggesting that transcriptional responses to
      hypoxia largely depend on pre-existing chromatin organization. Collectively our
      results show that large structural rearrangements establish chromatin
      architecture required for functional endothelium and this architecture remains
      largely unchanged in response to hypoxia.

PMID- 29216381
TI  - De novo gene evolution of antifreeze glycoproteins in codfishes revealed by whole
      genome sequence data.
AB  - New genes can arise through duplication of a pre-existing gene or de novo from
      non-coding DNA, providing raw material for evolution of new functions in response
      to a changing environment. A prime example is the independent evolution of
      antifreeze glycoprotein genes (afgps) in the Arctic codfishes and Antarctic
      notothenioids to prevent freezing. However, the highly repetitive nature of these
      genes complicates studies of their organization. In notothenioids, afgps evolved
      from an extant gene, yet the evolutionary origin of afgps in codfishes is
      unknown. Here, we demonstrate that afgps in codfishes have evolved de novo from
      non-coding DNA 13-18 Ma, coinciding with the cooling of the Northern Hemisphere.
      Using whole-genome sequence data from several codfishes and notothenioids, we
      find higher copy number of afgp in species exposed to more severe freezing
      suggesting a gene dosage effect. Notably, antifreeze function is lost in one
      lineage of codfishes analogous to the afgp losses in non-Antarctic notothenioids.
      This indicates that selection can eliminate the antifreeze function when freezing
      is no longer imminent. Additionally, we show that evolution of afgp-assisting
      antifreeze potentiating protein genes (afpps) in notothenioids coincides with
      origin and lineage-specific losses of afgp. The origin of afgps in codfishes is
      one of the first examples of an essential gene born from non-coding DNA in a non
      model species. Our study underlines the power of comparative genomics to uncover
      past molecular signatures of genome evolution, and further highlights the impact
      of de novo gene origin in response to a changing selection regime.

PMID- 29216380
TI  - Recent advances in intradural spinal tumors.
AB  - Intradural spinal tumors are rare tumors of the central nervous system. Due to
      the eloquence of the spinal cord and its tracts, the compact architecture of the
      cord and nerves, and the infiltrative nature of some of these tumors, surgical
      resection is difficult to achieve without causing neurological deficits.
      Likewise, chemotherapy and radiotherapy are utilized more cautiously in the
      treatment of intradural spinal tumors than their cranial counterparts. Targeted
      therapies aimed at the genetic alterations and molecular biology tailored to
      these tumors would be helpful but are lacking.Here, we review the major types of
      intradural spinal tumors, with an emphasis on genetic alterations, molecular
      biology, and experimental therapies for these difficult to treat neoplasms.

PMID- 29216382
TI  - Improving CRISPR-Cas specificity with chemical modifications in single-guide
      RNAs.
AB  - CRISPR systems have emerged as transformative tools for altering genomes in
      living cells with unprecedented ease, inspiring keen interest in increasing their
      specificity for perfectly matched targets. We have developed a novel approach for
      improving specificity by incorporating chemical modifications in guide RNAs
      (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence')
      and systematically evaluating their on-target and off-target activities in
      biochemical DNA cleavage assays and cell-based assays. Our results show that a
      chemical modification (2'-O-methyl-3'-phosphonoacetate, or 'MP') incorporated at
      select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce
      off-target cleavage activities while maintaining high on-target performance, as
      demonstrated in clinically relevant genes. These findings reveal a unique method
      for enhancing specificity by chemically modifying the guide sequence in gRNAs.
      Our approach introduces a versatile tool for augmenting the performance of CRISPR
      systems for research, industrial and therapeutic applications.

PMID- 29216383
TI  - Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga
      Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and
      Prevention FoodNet Study.
AB  - Background: Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin
      producing Escherichia coli (STEC) infection is a serious condition lacking
      specific treatment. Host immune dysregulation and genetic susceptibility to
      complement hyperactivation are implicated in non-STEC-related HUS. However,
      genetic susceptibility to D+HUS remains largely uncharacterized. Methods:
      Patients with culture-confirmed STEC diarrhea, identified through the Centers for
      Disease Control and Prevention FoodNet surveillance system (2007-2012), were
      serotyped and classified by laboratory and/or clinical criteria as having
      suspected, probable, or confirmed D+HUS or as controls and underwent genotyping
      at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic
      associations with D+HUS were explored by multivariable regression, with
      adjustment for known risk factors. Results: Of 641 enrollees with STEC O157:H7,
      80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve
      genes related to cytokine signaling, complement pathways, platelet function,
      pathogen recognition, iron transport, and endothelial function were associated
      with D+HUS in multivariable-adjusted analyses (P <= .05). Of 12 significant
      single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of
      D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064,
      and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with
      confirmed D+HUS (all P < .05). Conclusions: Polymorphisms in many non-complement
      related genes may contribute to D+HUS susceptibility. These results require
      replication, but they suggest novel therapeutic targets in patients with D+HUS.

PMID- 29216384
TI  - Featured Article: Evaluating Smartphone-Based Virtual Reality to Improve Chinese
      Schoolchildren's Pedestrian Safety: A Nonrandomized Trial.
AB  - Objective: This nonrandomized trial evaluated whether classroom-based training in
      a smartphone-based virtual reality (VR) pedestrian environment (a) teaches
      schoolchildren to cross streets safely, and (b) increases their self-efficacy for
      street-crossing. Methods: Fifty-six children, aged 8-10 years, attending primary
      school in Changsha, China participated. Baseline pedestrian safety assessment
      occurred in the VR environment and through unobtrusive observation of a subsample
      crossing a street for 11 days outside school. Self-efficacy was assessed through
      both self-report and observation. Following baseline, children engaged in the VR
      for 12 days in their classrooms, honing complex cognitive-perceptual skills
      required to engage safely in traffic. Follow-up assessment replicated baseline.
      Results: Probability of crash in the VR decreased posttraining (0.40 vs. 0.09),
      and observational data found the odds of looking at oncoming traffic while
      crossing the first lane of traffic increased (odds ratio [OR] = 2.4). Self
      efficacy increases occurred in self-report (proportional OR = 4.7 crossing busy
      streets) and observation of following crossing-guard signals (OR = 0.2, first
      lane). Conclusions: Pedestrian safety training via smartphone-based VR provides
      children the repeated practice needed to learn the complex skills required to
      cross streets safely, and also helps them improve self-efficacy to cross streets.
      Given rapid motorization and global smartphone penetration, plus epidemiological
      findings that about 75,000 children die annually worldwide in pedestrian crashes,
      smartphone-based VR could supplement existing policy and prevention efforts to
      improve global child pedestrian safety.

PMID- 29216385
TI  - De novo and secondary anaplastic meningiomas: a study of clinical and
      histomolecular prognostic factors.
AB  - Background: Following recent studies underlining the differences between de novo
      and secondary anaplastic meningiomas and the prognostic value of telomerase
      reverse transcriptase (TERT) promoter mutation, we decided to conduct a
      multicenter retrospective study to address these questions and determine specific
      prognostic factors in each of these 2 anaplastic meningioma subgroups. Methods:
      Among the 68 meningioma cases initially selected, only 57 were confirmed as
      anaplastic meningiomas after centralized pathological review. TERT promoter
      mutation analysis was performed in all cases. Results: Median overall survival
      was 2.6 years and 5-year survival rate was 10%. This study confirmed the better
      prognosis of de novo anaplastic meningiomas (28 tumors) compared with secondary
      anaplastic meningiomas (29 tumors) (P = 0.02). In the "de novo" group,
      meningiomas diagnosed on histological anaplasia alone had a better prognosis than
      those in patients with a high number of mitoses with or without anaplasia (P =
      0.01). In the "secondary" group, tumors demonstrate very heterogeneous clinical
      courses leading to malignant transformation, and time to first relapse as a low
      grade tumor was a strong predictor of overall survival (P = 0.0007). TERT
      promoter mutation in anaplastic meningiomas was rare (14%) and did not influence
      overall survival but was associated with a shorter recurrence-free survival in
      the secondary anaplastic meningioma subgroup (P = 0.02). The absence of TERT
      promoter methylation, although rare (3/33 cases), may be associated with
      prolonged overall survival (P = 0.02). Conclusion: This study highlights the
      different prognoses of de novo and secondary anaplastic meningiomas with specific
      prognostic factors in each subgroup. The analysis of TERT mutation and
      methylation could provide additional prognostic insights.

PMID- 29216386
TI  - An exome-wide association study identifies new susceptibility loci for age of
      smoking initiation in African- and European-American populations.
AB  - Introduction: Cigarette smoking is one of the largest causes of preventable death
      worldwide. This study aimed to identify susceptibility loci for age at smoking
      initiation (ASI) by performing exome-wide association analysis. Methods: A total
      of 2,510 smokers of either African-American (AA) or European-American (EA) origin
      were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and
      gene levels. After removal of those SNPs with minor allele frequency (<0.01),
      48,091 and 34,933 SNPs for AAs and EAs, respectively, were used to conduct single
      nucleotide polymorphism (SNP)-based association analysis. Gene-based analyses
      were then performed for all SNPs examined within each gene. Further, we estimated
      the proportion of variance explained by all common SNPs included in the analysis.
      Results: The strongest signals were detected for SNPs rs17849904 in the
      pitrilysin metallopeptidase 1 gene (PITRM1) in the AA sample (P=9.02*10-7) and
      rs34722354 in the discoidin domain of the receptor tyrosine kinase 2 gene (DDR2)
      in the EA sample (P = 9.74 * 10-7). Both SNPs remained significant after
      Bonferroni correction for the number of SNPs tested. Subsequently, gene-based
      association analysis revealed a significantly associated gene, DHRS7, in the AA
      sample (P = 5.00 * 10-6), a gene previously implicated in nicotine metabolism.
      Conclusions: Our study revealed two susceptibility loci for age of smoking
      initiation in the two ethnic samples, with the first being PITRM1 for AA smokers
      and the second DDR2 for EA smokers. In addition, we found DHRS7 to be a plausible
      candidate for ASI in the AA sample from our gene-based association analysis.
      Implications: PITRM1 and DHRS7 for African American smokers and DDR2 for European
      American smokers are new candidate genes for smoking initiation. These genes
      represent new additions to smoking initiation, an important but less studied
      phenotype in nicotine dependence research.

PMID- 29216387
TI  - USEFULNESS OF SIZE-SPECIFIC DOSE ESTIMATES IN PEDIATRIC COMPUTED TOMOGRAPHY:
      REVALIDATION OF LARGE-SCALE PEDIATRIC CT DOSE SURVEY DATA IN JAPAN.
AB  - The objective of this research is to calculate the organ equivalent dose and
      effective dose from the scanning conditions at 165 centers in Japan using
      computed tomography (CT) Dose software and compare the results with the CT dose
      index volume (CTDIvol), dose length product (DLP) and size-specific dose
      estimates (SSDE) to validate the usefulness of SSDE. The CTDIvol and DLP were
      significantly lower in infants than in children (p < 0.05). No significant
      differences were found in the bone marrow equivalent dose and effective dose for
      the torso between infants and children (p > 0.05), and the bone marrow equivalent
      dose and effective dose for the head were higher in infants than children (p <
      0.05). No significant difference was found in SSDE for the torso between infants
      and children (p > 0.05). Organ equivalent and effective doses for head CT scans
      are higher in infants than in children (I/P ratio >= 1). The I/P ratios of
      CTDIvol and DLP for chest and abdominal CT scans are also higher in Japan than in
      other countries. CTDIvol and DLP are not accurate when used as a dose index, and
      SSDE was considered suitable for dose assessment of the torso. However, for head
      CT in infants, a further reduction in radiation exposure is required.

PMID- 29216388
TI  - Insulin Resistance Disrupts the Interaction Between AKT and the NMDA Receptor and
      the Inactivation of the CaMKIV/CREB Pathway in Minimal Hepatic Encephalopathy.

PMID- 29216389
TI  - NEUTRON FIELD MEASUREMENT OF P(35)+Be SOURCE USING THE MULTI-FOIL ACTIVATION
      METHOD.
AB  - Neutron field from the p+Be interaction was investigated at the NPI CAS for a
      proton beam energy of 35 MeV and thick beryllium target. Broad neutron spectra at
      close source-to-sample distances were determined using the multi-foil activation
      technique. Two large sets of dosimetry foils containing the Ni, Co, Au, In, Ti,
      Al, Y, Lu, Nb and Fe were irradiated at a distance of 74 mm at direct neutron
      beam axis and at a distance of 34 mm from beam axis. Supporting Monte-Carlo MCNPX
      calculations of the irradiation system were performed as well. From measured
      reaction rates, the neutron energy spectra at both positions were reconstructed
      employing the modified version of the SAND-II unfolding code and activation cross
      section data from the EAF-2010 library. At the position of irradiated samples,
      the total fast neutron flux reaches the value up to 1010 cm-2 s-1, and the
      neutron field is utilizable for radiation hardness study and integral benchmark
      experiments within the International Fusion Material Irradiation Facility (IFMIF)
      program.

PMID- 29216390
TI  - DOSE AREA PRODUCT VALUES OF FLUOROSCOPICALLY GUIDED PAIN MANAGEMENT PROCEDURES:
      COMPARISON OF A BELGIAN TEACHING HOSPITAL WITH NATIONAL DIAGNOSTIC REFERENCE
      LEVELS.
AB  - In 2011, national diagnostic reference levels (DRLs) were proposed for pain
      management fluoroscopic procedures in Belgium. The primary goal of this work is
      to compare the dose area product values (DAP) recorded at the Saint-Luc
      University Hospital to these DRLs. From 2012 to 2015, 7664 interventional pain
      management procedures (4740 epidural, 2097 medial branch and 807 transforaminal
      infiltrations) were performed. Uni/multivariable analyses were done regarding the
      influence of different factors. The fluoroscopy duration and the DAP are lower to
      the DRLs (p < 0.001). From 7644 procedures' DAP, 1431 (18.7%) were higher than
      the DRLs: 1397 epidural (29.5%), 16 medial branch (0.8%) and 18 transforaminal
      infiltrations (2.2%) (p < 0.001 between procedures). The main factor that
      significantly modifies DAP, as duration, is the practitioner. Additionally, we
      obtained [IQR: 25-75] values for epidural [0.0174-0.055 mGy m2], medial branch
      block [0.0194-0.0472] and transforaminal infiltrations [0.0499-0.1067 mGy m2] (p
      < 0.05 vs. DRLs, respectively, 0.05, 0.25 and 0.3 mGy m2). Systematic use of
      contrast confirmation significantly increases DAP (p < 0.001). This retrospective
      analysis shows differences in DAP, mainly driven by the practitioner. This
      suggests the existence of modifiable factors. Programs aiming to determine these
      factors to reduce this DAP are justified.

PMID- 29216391
TI  - Prevalence and Determinants of REM Sleep Behavior Disorder in the General
      Population.
AB  - Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia associated
      with neurodegenerative synucleinopathies. Its prevalence is largely unknown. This
      study determined the prevalence and characteristics of RBD in the general
      population using gold-standard polysomnography. Methods: Full polysomnographic
      data from 1997 subjects (age=59+/-11.1 years, 53.6% women) participating in a
      population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Sleep
      related complaints and habits were investigated using various sleep measures
      including the Munich Parasomnia Screening (MUPS) questionnaire, which includes
      two questions evaluating complex motor behaviors suggestive of RBD. Full
      polysomnography was performed at home. For subjects screening positive for RBD,
      muscle activity during REM sleep was quantified to diagnose RBD. Results: 368
      participants endorsed dream-enactment behavior on either of the two MUPS
      questions, and 21 fulfilled polysomnographic criteria for RBD, resulting in an
      estimated prevalence of 1.06% (95% CI=0.61-1.50), with no difference between men
      and women. Compared to RBD- participants, RBD+ took more frequently
      antidepressants and antipsychotics (23.8% vs. 5.4%, p=0.005; 14.3% vs. 1.5%,
      p=0.004, respectively), and were more frequently smokers/ex-smokers (85% vs.
      56.6%, p=0.011). On polysomnography, RBD+ had more stage N2 sleep (52+/-11.5% vs.
      46.3+/-10.2%, p=0.024) and less REM sleep (18+/-6.4% vs. 21.9+/-6.2%, p=0.007),
      lower AHI in REM sleep (3.8+/-5.2 vs. 8.9+/-13/h, p=0.035) and lower autonomic
      arousal index (31+/-14.9 vs. 42.6+/-19.5/h, p=0.002). Conclusions: In our middle
      to-older age population-based sample, the prevalence of RBD was 1.06%, with no
      difference between men and women. RBD was associated with antidepressant and
      antipsychotic use and with minor differences in sleep structure.

PMID- 29216392
TI  - Dioxin-like PCB 126 Increases Systemic Inflammation and Accelerates
      Atherosclerosis in Lean LDL Receptor-Deficient Mice.
AB  - Exposure to dioxins and related persistent organic pollutants likely contributes
      to cardiovascular disease (CVD) risk through multiple mechanisms including the
      induction of chronic inflammation. Epidemiological studies have shown that leaner
      individuals may be more susceptible to the detrimental effects of lipophilic
      toxicants because they lack large adipose tissue depots that can accumulate and
      sequester these pollutants. This phenomenon complicates efforts to study
      mechanisms of pollutant-accelerated atherosclerosis in experimental animal models
      where high-fat feeding and adipose expansion limit the bioavailability of
      lipophilic pollutants. Here, we investigated whether a model dioxin-like
      pollutant, PCB 126, could increase inflammation and accelerate atherosclerosis in
      Ldlr-/- mice fed a low-fat atherogenic diet. We fed Ldlr-/- mice the
      Clinton/Cybulsky diet (10% kcal fat, 0.15% cholesterol) and sacrificed mice at 8,
      10, or 12 weeks postPCB (2 doses of 1 MUmol/kg) or vehicle gavage. To
      characterize this novel model, we examined the effects of PCB 126 on markers of
      systemic inflammation, hematological indices, fatty livers, and atherosclerotic
      lesion size. Mice exposed to PCB 126 exhibited significantly increased plasma
      inflammatory cytokine levels, increased circulating biomarkers of CVD, altered
      platelet, and red blood cell counts, increased accumulation of hepatic fatty
      acids, and accelerated atherosclerotic lesion formation in the aortic root. PCB
      126 also increased circulating neutrophils, monocytes, and macrophages as
      determined by flow cytometry analysis. Exposure to dioxin-like PCB 126 increases
      inflammation and accelerates atherosclerosis in mice. This low-fat atherogenic
      diet may provide a useful tool to study the mechanisms linking exposure to
      lipophilic pollutants to increased risk of CVD.

PMID- 29216393
TI  - MONTE CARLO SIMULATION OF OUT-OF-FIELD ORGAN DOSES AND CANCER RISK IN TANZANIA
      FOR RADIATION THERAPY OF UNILATERAL RETINOBLASTOMA USING A 60Co UNIT.
AB  - The use of 60Co teletherapy unit for the treatment of unilateral retinoblastoma
      (Rb) patients is a very common procedure in many developing countries including
      Tanzania. The aim of this study was to estimate organ-specific absorbed doses
      from an external beam radiation therapy 60Co unit for unilateral Rb and to assess
      the risks of the patients developing a secondary primary cancer. The absorbed
      dose estimations were based on a Monte Carlo method and a set of age-dependent
      computational male phantoms. The estimated doses were used to calculate the
      secondary cancer risks in out-of-field organs using the Biological Effects of
      Ionising Radiation VII risk models. The survival information and baseline cancer
      risks were based on relevant statistics for the Tanzanian population. The
      resulting out-of-field organ doses data showed that organs which are close to the
      target volume, such as the brain, salivary glands and thyroid glands, received
      the highest absorbed dose from scattered photons during the treatment of Rb. It
      was also found that the resulting photons dose to specific organs depends on the
      patient's age. Younger patients are more sensitive to radiation and also received
      higher dose contributions from the treatment head due to a larger part of the
      body exposed to the photon radiation. In all sites considered, the overall risks
      associated with radiation-induced secondary cancer were relatively lower than the
      baseline risks. Thus, the results in this article can help to provide good
      estimations of radiation-induced secondary cancer after radiation treatment of
      unilateral Rb using 60Co teletherapy unit in Tanzania and other developing
      countries.

PMID- 29216394
TI  - CircLRP6 Regulation of ZEB1 via miR-455 Is Involved in the Epithelial-Mesenchymal
      Transition During Arsenite-Induced Malignant Transformation of Human
      Keratinocytes.
AB  - Circular RNAs (circRNAs), a class of noncoding RNAs generated from pre-mRNAs,
      participate in the regulation of tumorigenesis. The mechanism for regulation,
      however, is unclear. Here, to determine whether circRNAs are involved in arsenite
      induced epithelial-mesenchymal transition (EMT) and malignant transformation in
      human keratinocyte (HaCaT) cells, the up-regulation of circLRP6 was confirmed in
      arsenite-transformed HaCaT (T-HaCaT) cells. In HaCaT cells, circLRP6 acted as an
      microRNA (miR)-455 sponge. For these cells, chronic exposure to arsenite caused
      an increase of circLRP6 and the transcription factor ZEB1, which induced the EMT.
      miR-455 suppressed the expression of ZEB1. Further, in T-HaCaT cells, knockdown
      of circLRP6 with siRNA inhibited ZEB1 expression, but cotransfection with
      circLRP6 siRNA and an miR-455 inhibitor reversed this inhibition. These results
      suggest that, in HaCaT cells, arsenite increases circLRP6 levels, which act as a
      sponge for miR-455 and up-regulate the miR-455 target, ZEB1, which subsequently
      induces the EMT, thus promoting malignant transformation. Thus, for HaCaT cells
      chronically exposed to arsenite, circLRP6 via miR-455 regulation of ZEB1 is
      involved in the EMT during malignant transformation. The results establish a
      previously unknown mechanism for arsenite-induced carcinogenesis.

PMID- 29216395
TI  - A Randomized Trial Evaluating the Prophylactic Activity of DSM265 Against
      Preerythrocytic Plasmodium falciparum Infection During Controlled Human Malarial
      Infection by Mosquito Bites and Direct Venous Inoculation.
AB  - Background: DSM265 is a selective inhibitor of Plasmodium dihydroorotate
      dehydrogenase that fully protected against controlled human malarial infection
      (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites when
      administered 1 day before challenge and provided partial protection when
      administered 7 days before challenge. Methods: A double-blinded, randomized,
      placebo-controlled trial was performed to assess safety, tolerability,
      pharmacokinetics, and efficacy of 1 oral dose of 400 mg of DSM265 before CHMI.
      Three cohorts were studied, with DSM265 administered 3 or 7 days before direct
      venous inoculation of sporozoites or 7 days before 5 bites from infected
      mosquitoes. Results: DSM265-related adverse events consisted of mild-to-moderate
      headache and gastrointestinal symptoms. DSM265 concentrations were consistent
      with pharmacokinetic models (mean area under the curve extrapolated to infinity,
      1707 ug*h/mL). Placebo-treated participants became positive by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) and were treated 7-10
      days after CHMI. Among DSM265-treated subjects, 2 of 6 in each cohort were
      sterilely protected. DSM265-treated recipients had longer times to development of
      parasitemia than placebo-treated participants (P < .004). Conclusions: This was
      the first CHMI study of a novel antimalarial compound to compare direct venous
      inoculation of sporozoites and mosquito bites. Times to qRT-PCR positivity and
      treatment were comparable for both routes. DSM265 given 3 or 7 days before CHMI
      was safe and well tolerated but sterilely protected only one third of
      participants.

PMID- 29216397
TI  - Madeiran Arabidopsis thaliana reveals ancient long-range colonization and
      clarifies demography in Eurasia.
AB  - The study of model organisms on islands may shed light on rare long-range
      dispersal events, uncover signatures of local evolutionary processes, and inform
      demographic inference on the mainland. Here, we sequenced the genomes of
      Arabidopsis thaliana samples from the oceanic island of Madeira. These samples
      include the most diverged worldwide, likely a result of long isolation on the
      island. We infer that colonisation of Madeira happened between 70 and 85 kya,
      consistent with a propagule dispersal model (of size > =10), or with an
      ecological window of opportunity. This represents a clear example of a natural
      long-range dispersal event in A. thaliana. Long-term effective population size on
      the island, rather than the founder effect, had the greatest impact on levels of
      diversity, and rates of coalescence. Our results uncover a selective sweep
      signature on the ancestral haplotype of a known translocation in Eurasia, as well
      as the possible importance of the low phosphorous availability in volcanic soils,
      and altitude, in shaping early adaptations to the island conditions. Madeiran
      genomes, sheltered from the complexities of continental demography, help
      illuminate ancient demographic events in Eurasia. Our data support a model in
      which two separate lineages of A. thaliana, one originating in Africa and the
      other from the Caucasus expanded and met in Iberia, resulting in a secondary
      contact zone there. While previous studies inferred that the westward expansion
      of A. thaliana coincided with the spread of human agriculture, our results
      suggest it happened much earlier (20-40 kya).

PMID- 29216399
TI  - Evolution of acidic mammalian chitinase genes (CHIA) is related to body mass and
      insectivory in primates.
AB  - Insects are an important food resource for many primates, but the chitinous
      exoskeletons of arthropods have long been considered to be indigestible by the
      digestive enzymes of most mammals. However, recently mice and insectivorous bats
      were found to produce the enzyme acidic mammalian chitinase (AMCase) to digest
      insect exoskeletons. Here, we report on the gene CHIA and its paralogs, which
      encode AMCase, in a comparative sample of nonhuman primates. Our results show
      that early primates likely had three CHIA genes, suggesting that insects were an
      important component of the ancestral primate diet. With some exceptions, most
      extant primate species retain only one functional CHIA paralog. The exceptions
      include two colobine species, in which all CHIA genes have premature stop codons,
      and several New World monkey species that retain two functional genes. The most
      insectivorous species in our sample also have the largest number of functional
      CHIA genes. Tupaia chinensis and Otolemur garnettii retain three functional CHIA
      paralogs, while Tarsius syrichta has a total of five, two of which may be
      duplications specific to the tarsier lineage. Selection analyses indicate that
      CHIA genes are under more intense selection in species with higher insect
      consumption, as well as in smaller-bodied species (<500 g), providing molecular
      support for Kay's Threshold, a well-established component of primatological
      theory which proposes that only small primates can be primarily insectivorous.
      These findings suggest that primates, like mice and insectivorous bats, may use
      the enzyme AMCase to digest the chitin in insect exoskeletons, providing
      potentially significant nutritional benefits.

PMID- 29216398
TI  - ATTED-II in 2018: A Plant Coexpression Database Based on Investigation of the
      Statistical Property of the Mutual Rank Index.
AB  - ATTED-II (http://atted.jp) is a coexpression database for plant species to aid in
      the discovery of relationships of unknown genes within a species. As an advanced
      coexpression analysis method, multispecies comparisons have the potential to
      detect alterations in gene relationships within an evolutionary context. However,
      determining the validity of comparative coexpression studies is difficult without
      quantitative assessments of the quality of coexpression data. ATTED-II (version
      9) provides 16 coexpression platforms for nine plant species, including seven
      species supported by both microarray- and RNA sequencing (RNAseq)-based
      coexpression data. Two independent sources of coexpression data enable the
      assessment of the reproducibility of coexpression. The latest coexpression data
      for Arabidopsis (Ath-m.c7-1 and Ath-r.c3-0) showed the highest reproducibility
      (Jaccard coefficient = 0.13) among previous coexpression data in ATTED-II. We
      also investigated the statistical basis of the mutual rank (MR) index as a
      coexpression measure by bootstrap sampling of experimental units. We found that
      the error distribution of the logit-transformed MR index showed normality with
      equal variances for each coexpression platform. Because the MR error was strongly
      correlated with the number of samples for the coexpression data, typical
      confidence intervals for the MR index can be estimated for any coexpression
      platform. These new, high-quality coexpression data can be analyzed with any tool
      in ATTED-II and combined with external resources to obtain insight into plant
      biology.

PMID- 29216396
TI  - Short-term efficacy and safety of rituximab therapy in refractory systemic lupus
      erythematosus: results from the British Isles Lupus Assessment Group Biologics
      Register.
AB  - Objectives: To describe the baseline characteristics of SLE patients requiring
      biologic therapy in the UK and to explore short term efficacy and infection rates
      associated with rituximab (RTX) use. Methods: Patients commencing biologic
      therapy for refractory SLE and who consented to join BILAG-BR were analysed.
      Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of
      infection over follow-up were analysed. Response was defined as loss of all A and
      B BILAG scores to ? 1 B score with no new A/B scores in other organ systems at 6
      months. Results: Two hundred and seventy SLE patients commenced biologic therapy
      from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred
      and fifty (93%) patients were taking glucocorticoids at baseline at a median
      [interquartile range (IQR)] oral dose of 10 mg (5-20 mg) daily. Response rates at
      6 months were available for 68% of patients. The median (IQR) BILAG score was 15
      (10-23) at baseline and 3 (2-12) at 6 months (P < 0.0001). The median (IQR)
      SLEDAI-2K reduced from 8 (5-12) to 4 (0-7) (P < 0.001). Response was achieved in
      49% of patients. There was also a reduction in glucocorticoid use to a median
      (IQR) dose of 7.5 mg (5-12 mg) at 6 months (P < 0.001). Serious infections
      occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX
      therapy. A higher proportion of early infections were non-respiratory (odds ratio
      = 1.98, 95% CI: 0.99, 3.9; P = 0.049). Conclusion: RTX is safe and is associated
      with improvement in disease activity in refractory SLE patients with concomitant
      reductions in glucocorticoid use. Early vigilance for infection post-infusion is
      important to further improve treatment risks and benefits.

PMID- 29216400
TI  - Activity and safety of crizotinib in patients with alveolar soft part sarcoma
      with rearrangement of TFE3: European Organization for Research and Treatment of
      Cancer (EORTC) phase II trial 90101 'CREATE'.
AB  - Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated
      with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET
      gene expression. We prospectively assessed the efficacy and safety of the MET
      tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic
      ASPS. Patients and methods: Eligible patients with reference pathology-confirmed
      ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of
      a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The
      primary end point was the objective response rate (ORR) according to local
      investigator. Secondary end points included duration of response, disease control
      rate (DCR), progression-free survival (PFS), progression-free rate, overall
      survival (OS) and safety. Results: Among 53 consenting patients, all had a
      centrally confirmed ASPS and 48 were treated. A total of 45 were eligible,
      treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial
      response (PR) that lasted 215 days and 35 had stable disease (SD) as best
      response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+
      cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI
      22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET-
      patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI
      0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in
      MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI
      12.8% to 96.1%). One patient with unknown MET status due to technical failure
      achieved SD but stopped treatment due to progression after 17 cycles. The most
      common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting
      [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and
      fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for
      Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue
      sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged
      ASPS MET+ patients. Clinical trial number: EORTC 90101, NCT01524926.

PMID- 29216401
TI  - Sink-Source Balance and Down-Regulation of Photosynthesis in Raphanus sativus:
      Effects of Grafting, N and CO2.
AB  - To clarify whether excessive accumulation of total non-structural carbohydrate
      (TNC) causes down-regulation of photosynthesis in Raphanus sativus, we
      manipulated sink-source balance to alter TNC levels in source leaves and examined
      its effects on photosynthetic characteristics, whole-plant biomass allocation and
      anatomical characteristics of leaves and petioles. Comet and Leafy varieties with
      large and small hypocotyls were reciprocally grafted to change hypocotyl sink
      strength. They were grown at high or low nitrogen (N) availability and at
      elevated or ambient CO2. Maximum photosynthetic rate, which was highly correlated
      with Rubisco and leaf N contents, was hardly correlated with TNC across the
      grafting combinations and growth conditions. Biomass allocation to petioles and
      hypocotyls and accumulation of TNC in each organ were significantly higher at low
      N. TNC and structural carbohydrates such as cellulose and hemicellulose were
      higher and the proportion of intercellular air space in source leaves was lower
      at low N and elevated CO2. We conclude that excess TNC does not cause severe down
      regulation of photosynthesis, and cell walls and petioles are also major
      carbohydrate sinks responding to changes in sink-source and carbon-nitrogen
      balances, which contribute to alleviating further accumulation of TNC to avoid
      its negative effects in source leaves.

PMID- 29216402
TI  - Soyasaponins: A New Class of Root Exudates in Soybean (Glycine max).
AB  - Root exudates are plant metabolites secreted from the roots into the soil. These
      exudates are involved in many important biological processes, including
      acquisition of nutrients, defense and signaling to rhizosphere bacteria, such as
      isoflavones of soybean crucial for the symbiosis with rhizobium. Less is known,
      however, about other types of root exudates. This study shows that soybean roots
      secrete large amounts of soyasaponins (triterpenoid glycosides) as root exudates.
      The soyasaponins are classified into four groups, with group A being the most
      secreted of these compounds, whereas DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H
      pyran-4-one) soyasaponins is the group showing greatest accumulation in root
      tissues, suggesting a selection system for secreted compounds. Time-course
      experiments showed that the soyasaponin secretion peaked during early vegetative
      stages. In particular, soyasaponin Ah was the major compound secreted by soybean
      roots, whereas the deacetylated derivative Af was the major compound secreted
      specifically during the VE stage. The secretion of soyasaponins containing
      glycosyl moieties is an apparent loss of photosynthates. This phenomenon has been
      also observed in other legume species, although the composition of secreted
      soyasaponins is plant species dependent. The identification of triterpenoid
      saponins as major metabolites in legume root exudates will provide novel insights
      into chemical signaling in the rhizosphere between plants and other organisms.

PMID- 29216403
TI  - Staphylococcus aureus Impacts Pseudomonas aeruginosa Chronic Respiratory Disease
      in Murine Models.
AB  - Background: Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial
      pathogens of the respiratory tract in patients with cystic fibrosis (CF).
      Although P. aeruginosa chronic bronchial infection is associated with a poorer
      prognosis, the consequences of S. aureus colonization on CF outcomes are
      controversial. Methods: In this paper, murine models of infection resembling
      traits of the CF human airways disease have been revisited using an infection
      schedule that mimics the sequence of events of pulmonary disease in CF patients.
      First, mice were infected with S. aureus, embedded in agar beads; this was
      followed by P. aeruginosa infection and analysis of bacterial load, leukocyte
      infiltration, and lung tissue damage. Results: We reveal that (1) S. aureus
      promotes severe lesions including abscess formation, (2) S. aureus increases the
      risk of subsequent chronic P. aeruginosa respiratory infection, and (3) once the
      chronic infection has been established, P. aeruginosa influences most of the
      inflammatory responses independent of S. aureus. Conclusions: Our findings
      established the significance of S. aureus colonization per se and the impact on
      the subsequent P. aeruginosa infection. This would point towards a thorough
      assessment for the need of treatment against S. aureus.

PMID- 29216404
TI  - EXPOSURE TO EXTREMELY LOW FREQUENCY ELECTROMAGNETIC FIELDS DURING LESSONS IN
      SECONDARY SCHOOLS.
AB  - Schools are a significant location where children are exposed to electromagnetic
      fields (EMFs), which may cause adverse health effects. This cross-sectional study
      aimed to examine exposure levels to extremely low frequency magnetic fields (ELF
      MFs) with a range of 5 Hz-32 kHz, and ELF-electric fields (ELF-EFs) with a range
      of 5 Hz-2 kHz in secondary schools in Bangkok, Thailand. This study was conducted
      in 60 classrooms from three schools during class hours. Spot measurements were
      taken with a Narda EFA 300 field analyzer to evaluate exposure levels. This study
      showed that ELF-EMF exposure levels are lower than ICNIRP guidelines, while
      21.67% of classrooms had a magnetic field strength above 0.2 MUT, and the main
      sources of ELF-EMFs were electrical equipment and electrical wiring. Future
      studies should measure ELF-EMF levels in other areas and evaluate the effects of
      long term exposure to ELF-EMFs on children's health.

PMID- 29216406
TI  - High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a
      Statistical Approach to Characterize Effects on Steroidogenesis.
AB  - The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program
      and the Organization for Economic Co-operation and Development (OECD) have used
      the human adrenocarcinoma (H295R) cell-based assay to predict chemical
      perturbation of androgen and estrogen production. Recently, a high-throughput
      H295R (HT-H295R) assay was developed as part of the ToxCast program that includes
      measurement of 11 hormones, including progestagens, corticosteroids, androgens,
      and estrogens. To date, 2012 chemicals have been screened at 1 concentration; of
      these, 656 chemicals have been screened in concentration-response. The objectives
      of this work were to: (1) develop an integrated analysis of chemical-mediated
      effects on steroidogenesis in the HT-H295R assay and (2) evaluate whether the HT
      H295R assay predicts estrogen and androgen production specifically via comparison
      with the OECD-validated H295R assay. To support application of HT-H295R assay
      data to weight-of-evidence and prioritization tasks, a single numeric value based
      on Mahalanobis distances was computed for 654 chemicals to indicate the magnitude
      of effects on the synthesis of 11 hormones. The maximum mean Mahalanobis distance
      (maxmMd) values were high for strong modulators (prochloraz, mifepristone) and
      lower for moderate modulators (atrazine, molinate). Twenty-five of 28 reference
      chemicals used for OECD validation were screened in the HT-H295R assay, and
      produced qualitatively similar results, with accuracies of 0.90/0.75 and
      0.81/0.91 for increased/decreased testosterone and estradiol production,
      respectively. The HT-H295R assay provides robust information regarding estrogen
      and androgen production, as well as additional hormones. The maxmMd from this
      integrated analysis may provide a data-driven approach to prioritizing lists of
      chemicals for putative effects on steroidogenesis.

PMID- 29216405
TI  - The Human Immunodeficiency Virus Care Continuum in China: 1985-2015.
AB  - Background: Human immunodeficiency virus (HIV) care continuum attrition is a
      major global public health challenge. Few studies have examined this problem in
      resource-limited settings. We aimed to assess cumulative, current, and historical
      achievement along China's HIV continuum of care. Methods: A nationwide, serial
      cross-sectional study of all individuals with HIV infection diagnosed in China
      between 1 January 1985 and 31 December 2015 was conducted using data from China's
      HIV/AIDS information systems. Biennial estimates of the number of persons living
      with HIV were also used. We defined 7 steps in HIV care continuum as infected
      (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral
      therapy (ART), and virally suppressed. Cumulative, 30-year performance, and
      biennial performance during the most recent 10 years were examined. Results: A
      total of 573529 persons diagnosed with HIV infection were included. Cumulatively,
      94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART,
      and 44% were suppressed. Greatest attrition was observed for adolescents,
      minorities, and those who reported injecting drug use as their route of
      infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68%
      among those infected were diagnosed, 67% among diagnosed were receiving ART, and
      65% among those receiving ART were virally suppressed. After adjusting for those
      without viral load testing, the proportion suppressed increased to 89%.
      Conclusions: Despite dramatic improvements, China faces serious challenges in
      achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets,
      because of substantial attrition along its continuum of HIV care.

PMID- 29216408
TI  - A cold responsive ethylene responsive factor from Medicago falcata confers cold
      tolerance by up-regulation of polyamine turnover, antioxidant protection, and
      proline accumulation.
AB  - Ethylene responsive factor (ERF) subfamily transcription factors play an
      important role in plant abiotic and biotic stress tolerance. A cold responsive
      ERF, MfERF1, was isolated from Medicago falcata, an important forage legume that
      has great cold tolerance. Overexpression of MfERF1 resulted in an increased
      tolerance to freezing and chilling in transgenic tobacco plants, whereas down
      regulation of the ortholog of MfERF1 in Medicago truncatula resulted in reduced
      freezing tolerance in RNAi plants. Higher transcript levels of some stress
      responsive genes (CHN50, OSM, ERD10C, and SAMS) and those involved in spermidine
      (Spd) and spermine (Spm) synthesis (SAMDC1, SAMDC2, SPDS1, SPDS2, and SPMS) and
      catabolism (PAO) were observed in transgenic plants than in wild type. However,
      neither Spd nor Spm level was accumulated in transgenic plants as a result of
      promoted polyamine oxidase activity. Transgenic plants had higher activities of
      antioxidants associated with the induced encoding genes including Cu, Zn-SOD,
      CAT1, CAT2, CAT3, and cpAPX and accumulated more proline associated with induced
      P5CS and reduced PROX2 transcription as compared with wild type. The results
      suggest that MfERF1 confers cold tolerance through promoted polyamine turnover,
      antioxidant protection, and proline accumulation.

PMID- 29216407
TI  - An open-label positron emission tomography study to evaluate serotonin
      transporter occupancy following escalating dosing regimens of (R)-(-)-O
      desmethylvenlafaxine and racemic O-desmethylvenlafaxine.
AB  - SEP-227162 [R(-)-O-desmethylvenlafaxine] is an enantiomer of the venlafaxine
      metabolite O-desmethylvenlafaxine (ODV, PristiqTM, Wyeth). This study compared
      the serotonin transporter (SERT) occupancy achieved by SEP-227162 and ODV, at
      daily doses of 25, 50, 100, and 150 mg using [11 C]DASB positron emission
      tomography (PET). Sixteen healthy male subjects participated in one of four dose
      groups (N = 4 per group) during which they were administered two doses of the
      study drug (SEP-227162 or ODV). For each study drug, total daily doses of 25, 50,
      100, and150 mg were studied. Subjects underwent three PET scans with [11 C]DASB.
      A baseline, off-medication, scan was performed prior to dosing and a [11 C]DASB
      PET scan was performed after 72 hr at each dose level. [11 C]DASB binding
      potential (BPND ) was calculated using the simplified reference tissue method.
      SERT occupancy was calculated as the change in BPND (DeltaBPND ) from baseline
      scan to the on-medication scan relative to the baseline BPND value. SEP-227162
      and ODV significantly reduced regional distribution volumes and region BPND
      values in a dose-dependent manner. Across all doses ODV produced significantly
      greater SERT occupancy than SEP-227162 (ANOVA F = 21.8, df = 1,23, p < .001). The
      total daily dose required to provide 50% SERT occupancy was 24.8 mg for SEP
      227162 and 14.4 mg for ODV. In vitro data suggests a ratio of 3.3:1 for binding
      at human SERT for SEP-227162 relative to ODV. Our study suggests a ratio of
      1.7:1, highlighting the value of in vivo imaging in the drug development process.

PMID- 29216410
TI  - Three-dimensional ultrastructure of chloroplast pockets formed under salinity
      stress.
AB  - We investigated the invagination structure of a chloroplast that surrounds
      organelles such as mitochondria and peroxisomes within a thin layer of
      chloroplast stroma, which is called a chloroplast pocket. In this study,
      chloroplast pockets were observed in rice plants subjected to salinity stress but
      not under moderate growth condition. They included cytosol, transparent
      structure, lipid bodies, mitochondria, and peroxisomes. We constructed the three
      dimensional architecture of chloroplast pockets by using serial images obtained
      by transmission electron microscopy and focused ion beam-scanning electron
      microscopy. Three types of chloroplast pockets were observed by transmission
      electron microscopy: Organelles were completely enclosed in a chloroplast pocket
      (enclosed type), a chloroplast pocket with a small gap in the middle part (gap
      type), and a chloroplast pocket with one side open (open type). Of the 70 pockets
      observed by serial imaging, 35 were enclosed type, and 21 and 14 were gap and
      open types, respectively. Mitochondria and peroxisomes were often in contact with
      the chloroplast pockets. Focused ion beam-scanning electron microscopy revealed
      chloroplasts with a sheet structure partially surrounding peroxisomes. This fact
      suggests that chloroplasts might construct large sheet structures that would be
      related to the formation of chloroplast pockets.

PMID- 29216409
TI  - Enhanced Turnover for the P450 119 Peroxygenase-Catalyzed Asymmetric Epoxidation
      of Styrenes by Random Mutagenesis.
AB  - A randomized library is constructed based on pET30a-CYP119-T214V plasmid. This
      library of random mutants of CYP119-T214V was screened by means of the reduced CO
      difference spectra and epoxidation of styrene. By using directed evolution, a new
      CYP119 quadruple mutant S148P/I161T/K199E/T214V is constructed, expressed, and
      purified. This quadruple mutant significantly increases the turnover rate and
      conversion for the asymmetric epoxidation of styrene and its derivatives. The
      kcat. value of cis-beta-methylstyrene epoxidation catalyzed by the quadruple
      mutant exhibits an approximately 10-fold increase, relative to the previously
      reported T213M mutant under the same conditions. This is the first engineered
      CYP119 peroxygenase for the epoxidation of cis-beta-methylstyrene with a high
      turnover rate. The proposed mechanism, on the basis of a molecular docking study,
      for the asymmetric epoxidation suggests that the introduction of an acidic amino
      acid side chain into the active site and a hydrophobic amino acid into the
      substrate channels of CYP119 peroxygenase might result in high efficiency for the
      formation of compound I, and its subsequent peroxygenation by reconstructing the
      hydrogen-bonding interaction and increasing the substrate affinity and access.

PMID- 29216411
TI  - Electrochemical Properties of Boron-Doped Fullerene Derivatives for Lithium-Ion
      Battery Applications.
AB  - The high electron affinity of fullerene C60 coupled with the rich chemistry of
      carbon makes it a promising material for cathode applications in lithium-ion
      batteries. Since boron has one electron less than carbon, the presence of boron
      on C60 cages is expected to generate electron deficiency in C60 , and thereby to
      enhance its electron affinity. By using density functional theory (DFT), we
      studied the redox potentials and electronic properties of C60 and C59 B. We have
      found that doping C60 with one boron atom results in a substantial increase in
      redox potential from 2.462 V to 3.709 V, which was attributed to the formation of
      an open shell system. We also investigated the redox and electronic properties of
      C59 B functionalized with various redox-active oxygen containing functional
      groups (OCFGs). For the combination of functionalization with OCFGs and boron
      doping, it is found that the enhancement of redox potential is reduced, which is
      mainly attributed to the open shell structure being changed to a closed-shell
      one. Nevertheless, the redox potentials are still higher than that of pristine
      C60 . From the observation that the lowest unoccupied molecular orbital of closed
      shell OCFG- functionalized C59 B is correlated well with the redox potential, it
      was confirmed that the spin state is crucial to be considered to understand the
      relationship between electronic structure and redox properties.

PMID- 29216413
TI  - Quantum Machine Learning in Chemical Compound Space.
AB  - Rather than numerically solving the computationally demanding equations of
      quantum or statistical mechanics, machine learning methods can infer approximate
      solutions, interpolating previously acquired property data sets of molecules and
      materials. The case is made for quantum machine learning: An inductive molecular
      modeling approach which can be applied to quantum chemistry problems.

PMID- 29216412
TI  - Insights into ablation of persistent atrial fibrillation: Lessons from 6-year
      clinical outcomes.
AB  - INTRODUCTION: Ablation of persistent atrial fibrillation (AF) is a potential
      treatment option for symptomatic patients. We sought to evaluate the critical
      role of circumferential pulmonary vein isolation (CPVI) in the ablation of
      persistent AF. METHODS AND RESULTS: A total of 341 ablation procedures were
      performed in 174 consecutive patients with persistent AF. CPVI was performed in
      all patients, additional ablation was only performed if electrical cardioversion
      failed after CPVI. During a median follow-up (FU) of 89 (63; 89) months, stable
      sinus rhythm was documented in 42/170 (25%) patients after a single procedure and
      in 111/164 (68%) patients after 1.9 +/- 1.1 procedures. Stable SR was achieved in
      40/75 (53%) patients in whom only CPVI was performed during the index and repeat
      procedures and in 71/89 (79%) patients with CPVI plus additional ablation. The
      main predictor for ablation success was duration of persistent AF before the
      index procedure (P < 0.001, HR +/- CI: 1.608 [1.034, 1.103]). Responders to CPVI
      during the initial procedure had a significantly better multiple-procedure
      outcome after 42 months of FU compared to CPVI nonresponders (P  =  0.0365).
      Conversion during the index procedure had no impact on clinical outcomes (P  = 
      0.0903). Persistent AF regressed to paroxysmal AF in 16% of patients.
      CONCLUSIONS: We demonstrate a 25% single- and 68% multiple-procedure success in
      patients with persistent AF, while stable SR was achieved in 53% of patients with
      pure CPVI during all procedures and in 79% of patients with CPVI plus additional
      ablation. Only duration of persistent AF before ablation had a statistically
      significant impact on ablation outcome.

PMID- 29216414
TI  - Dry and wet periods drive rapid shifts in community assembly in an estuarine
      ecosystem.
AB  - The impacts of changing climate regimes on emergent processes controlling the
      assembly of ecological communities remain poorly understood. Human alterations to
      the water cycle in the western United States have resulted in greater interannual
      variability and more frequent and severe extremes in freshwater flow. The
      specific mechanisms through which such extremes and climate regime shifts may
      alter ecological communities have rarely been demonstrated, and baseline
      information on current impacts of environmental variation is widely lacking for
      many habitats and communities. Here, we used observations and experiments to show
      that interannual variation in winter salinity levels in San Francisco Bay
      controls the mechanisms determining sessile invertebrate community composition
      during the following summer. We found consistent community changes in response to
      decadal-scale dry and wet extremes during a 13-year period, producing strikingly
      different communities. Our results match theoretical predictions of major shifts
      in species composition in response to environmental forcing up to a threshold,
      beyond which we observed mass mortality and wholesale replacement of the former
      community. These results provide a window into potential future community
      changes, with environmental forcing altering communities by shifting the relative
      influences of the mechanisms controlling species distributions and abundances. We
      place these results in the context of historical and projected future
      environmental variation in the San Francisco Bay Estuary.

PMID- 29216415
TI  - A Cesium Rare-Earth Silicate Cs3 RESi6 O15 (RE=Dy-Lu, Y, In): The Parent of an
      Unusual Structural Class Featuring a Remarkable 57 A Unit Cell Axis.
AB  - The structure of Cs3 RESi6 O15 , where RE=Dy-Lu, Y, In, is unusual in that it
      contains octahedrally coordinated rare-earth ions; their relative orientation
      dictates the structure, as they rotate about the c-axis supported by the cyclic
      Si6 O15 framework. The repeat unit of the rotation is eight units generating a
      very long (ca. 57 A) unit cell axis. This unusual repeat unit is created by the
      structural flexibility of the hexasilicate ring, which is in turn affected by the
      size of the rare earth ion as well as the size of alkali ion residing within the
      silicate layers. Previous work showed for the smaller Sc3+ ion, the rotation of
      the octahedra is not sufficient to achieve closure at an integral repeat unit and
      an incommensurate structure results. The products are prepared as large, high
      quality single crystals using a high-temperature (650  degrees C) hydrothermal
      method with CsOH and F- mineralizers. The presence of fluoride is essential to
      the formation of the product.

PMID- 29216416
TI  - Illuminating the role of the Galpha heterotrimeric G protein subunit, RGA1, in
      regulating photoprotection and photoavoidance in rice.
AB  - We studied physiological mechanisms of photoavoidance and photoprotection of a
      dwarf rice mutant with erect leaves, d1, in which the RGA1 gene, which encodes
      the Galpha subunit of the heterotrimeric G protein, is non-functional. Leaves of
      d1 exhibit lower leaf temperature and higher photochemical reflectance index
      relative to wild type (WT), indicative of increased photoavoidance and more
      efficient light harvesting. RNA sequencing analysis of flag leaves revealed that
      messenger RNA levels of genes encoding heat shock proteins, enzymes associated
      with chlorophyll breakdown, and ROS scavengers were down-regulated in d1. By
      contrast, genes encoding proteins associated with light harvesting, Photosystem
      II, cyclic electron transport, Photosystem I, and chlorophyll biosynthesis were
      up-regulated in d1. Consistent with these observations, when WT and d1 plants
      were experimentally subjected to the same light intensity, d1 plants exhibited a
      greater capacity to dissipate excess irradiance (increased nonphotochemical
      quenching) relative to WT. The increased capacity in d1 for both photoavoidance
      and photoprotection reduced sustained photoinhibitory damage, as revealed by a
      higher Fv /Fm . We therefore propose RGA1 as a regulator of photoavoidance and
      photoprotection mechanisms in rice and highlight the prospect of exploiting
      modulation of heterotrimeric G protein signalling to increase these
      characteristics and improve the yield of cereals in the event of abiotic stress.

PMID- 29216417
TI  - Feasibility of small group cognitive rehabilitation in a clinical cancer setting.

PMID- 29216418
TI  - Medication Adherence Decisions in Patients With Schizophrenia.
AB  - Medication nonadherence is common in patients with schizophrenia. Nonadherence
      affects approximately half of all patients and may increase the risk of relapse
      and hospitalization. Although it is an intensively studied phenomenon, we have
      little understanding of underlying mechanisms leading to nonadherence. In this
      article, using quantitative and qualitative study results and psychological
      decision theory, we present a model of medication adherence decisions in patients
      with schizophrenia that may be useful for clinicians and those involved in the
      development of adherence interventions or adherence research. The model focuses
      on the function and meaning of medication from a patient perspective. Although
      the model is a simplified description of the decision-making process related to
      medication use, it does explain the role of some important aspects such as
      insight, side effects, efficacy, and social influences. We also discuss how this
      may explain the high and persistent rates of nonadherence. Finally, we discuss
      some implications for clinical practice..

PMID- 29216419
TI  - Frequent, Spontaneous, Prolonged Penile Erections in a 12-Year-Old Boy After
      Lisdexamfetamine Use.

PMID- 29216420
TI  - ERRATUM: Comparison of Surgery Plus Chemotherapy and Palliative Chemotherapy
      Alone for Advanced Gastric Cancer with Krukenberg Tumor.
AB  - [This corrects the article on p. 697 in vol. 47.].

PMID- 29216421
TI  - Multidimensional Quantum Mechanical Modeling of Electron Transfer and Electronic
      Coherence in Plant Cryptochromes: The Role of Initial Bath Conditions.
AB  - A multidimensional quantum mechanical protocol is used to describe the
      photoinduced electron transfer and electronic coherence in plant cryptochromes
      without any semiempirical, e.g., experimentally obtained, parameters. Starting
      from a two-level spin-boson Hamiltonian we look at the effect that the initial
      photoinduced nuclear bath distribution has on an intermediate step of this
      biological electron transfer cascade for two idealized cases. The first assumes a
      slow equilibration of the nuclear bath with respect to the previous electron
      transfer step that leads to an ultrafast decay with little temperature
      dependence; while the second assumes a prior fast bath equilibration on the donor
      potential energy surface leading to a much slower decay, which contrarily
      displays a high temperature dependence and a better agreement with previous
      theoretical and experimental results. Beyond Marcus and semiclassical pictures
      these results unravel the strong impact that the presence or not of equilibrium
      initial conditions has on the electronic population and coherence dynamics at the
      quantum dynamics level in this and conceivably in other biological electron
      transfer cascades.

PMID- 29216422
TI  - Distinguishing Petroleum (Crude Oil and Fuel) From Smoke Exposure within
      Populations Based on the Relative Blood Levels of Benzene, Toluene, Ethylbenzene,
      and Xylenes (BTEX), Styrene and 2,5-Dimethylfuran by Pattern Recognition Using
      Artificial Neural Networks.
AB  - Studies of exposure to petroleum (crude oil/fuel) often involve monitoring
      benzene, toluene, ethylbenzene, xylenes (BTEX), and styrene (BTEXS) because of
      their toxicity and gas-phase prevalence, where exposure is typically by
      inhalation. However, BTEXS levels in the general U.S. population are primarily
      from exposure to tobacco smoke, where smokers have blood levels on average up to
      eight times higher than nonsmokers. This work describes a method using partition
      theory and artificial neural network (ANN) pattern recognition to classify
      exposure source based on relative BTEXS and 2,5-dimethylfuran blood levels. A
      method using surrogate signatures to train the ANN was validated by comparing
      blood levels among cigarette smokers from the National Health and Nutrition
      Examination Survey (NHANES) with BTEXS and 2,5-dimethylfuran signatures derived
      from the smoke of machine-smoked cigarettes. Classification agreement for an ANN
      model trained with relative VOC levels was up to 99.8% for nonsmokers and 100.0%
      for smokers. As such, because there is limited blood level data on individuals
      exposed to crude oil/fuel, only surrogate signatures derived from crude oil and
      fuel were used for training the ANN. For the 2007-2008 NHANES data, the ANN model
      assigned 7 out of 1998 specimens (0.35%) and for the 2013-2014 NHANES data 12 out
      of 2906 specimens (0.41%) to the crude oil/fuel signature category.

PMID- 29216424
TI  - Low Temperature Synthesis and Phosphorescence of Methylcyanotriacetylene.
AB  - This paper reports on UV-stimulated synthesis of methylcyanotriacetylene carried
      out in cryogenic rare gas matrixes via coupling of smaller precursors: propyne
      and cyanodiacetylene. The detection was possible due to the strong visible a 3A' 
      > X 1A1 phosphorescence of CH3C7N, discovered in the course of this work. The
      ensuing measurements of electronic spectroscopy revealed the formally forbidden B
      1E-X 1A1 system, as well as the allowed one E 1A1-X 1A1, with origins at
      approximately 3.32 and 5.4 eV, respectively. It was also possible to revisit the
      spectroscopic characterization of cyanotriacetylene, HC7N, formed in parallel to
      the title photoproduct. Spectral assignments were assisted with a density
      functional theory study.

PMID- 29216423
TI  - Nanoparticle Functionalization with Platelet Membrane Enables Multifactored
      Biological Targeting and Detection of Atherosclerosis.
AB  - Cardiovascular disease represents one of the major causes of death across the
      global population. Atherosclerosis, one of its most common drivers, is
      characterized by the gradual buildup of arterial plaque over time, which can
      ultimately lead to life-threatening conditions. Given the impact of the disease
      on public health, there is a great need for effective and noninvasive imaging
      modalities that can provide valuable information on its biological underpinnings
      during development. Here, we leverage the role of platelets in atherogenesis to
      design nanocarriers capable of targeting multiple biological elements relevant to
      plaque development. Biomimetic nanoparticles are prepared by coating platelet
      membrane around a synthetic nanoparticulate core, the product of which is capable
      of interacting with activated endothelium, foam cells, and collagen. The effects
      are shown to be exclusive to platelet membrane-coated nanoparticles. These
      biomimetic nanocarriers are not only capable of efficiently localizing to well
      developed atherosclerotic plaque, but can also target subclinical regions of
      arteries susceptible to plaque formation. Using a commonly employed magnetic
      resonance imaging contrast agent, live detection is demonstrated using an animal
      model of atherosclerosis. Ultimately, this strategy may be leveraged to better
      assess the development of atherosclerosis, offering additional information to
      help clinicians better manage the disease.

PMID- 29216426
TI  - Epoxy Nanocomposites Containing Zeolitic Imidazolate Framework-8.
AB  - Zeolitic imidazole framework-8 (ZIF-8) is utilized as a functional filler and a
      curing agent in the preparation of epoxy nanocomposites. The imidazole group on
      the surface of the ZIF-8 initiates epoxy curing, resulting in covalent bonding
      between the ZIF-8 crystals and epoxy matrix. A substantial reduction in
      dielectric constant and increase in tensile modulus were observed. The
      implication of the present study for utilization of metal-organic framework to
      improve physical and mechanical properties of polymeric matrixes is discussed.

PMID- 29216425
TI  - Replacing the Ethylmalonyl-CoA Pathway with the Glyoxylate Shunt Provides
      Metabolic Flexibility in the Central Carbon Metabolism of Methylobacterium
      extorquens AM1.
AB  - The ethylmalonyl-CoA pathway (EMCP) is an anaplerotic reaction sequence in the
      central carbon metabolism of numerous Proteo- and Actinobacteria. The pathway
      features several CoA-bound mono- and dicarboxylic acids that are of interest as
      platform chemicals for the chemical industry. The EMCP, however, is essential for
      growth on C1 and C2 carbon substrates and therefore cannot be simply interrupted
      to drain these intermediates. In this study, we aimed at reengineering central
      carbon metabolism of the Alphaproteobacterium Methylobacterium extorquens AM1 for
      the specific production of EMCP derivatives in the supernatant. Establishing a
      heterologous glyoxylate shunt in M. extorquens AM1 restored wild type-like growth
      in several EMCP knockout strains on defined minimal medium with acetate as carbon
      source. We further engineered one of these strains that carried a deletion of the
      gene encoding crotonyl-CoA carboxylase/reductase to demonstrate in a proof-of
      concept the specific production of crotonic acid in the supernatant on a defined
      minimal medium. Our experiments demonstrate that it is in principle possible to
      further exploit the EMCP by establishing an alternative central carbon metabolic
      pathway in M. extorquens AM1, opening many possibilities for the biotechnological
      production of EMCP-derived compounds in future.

PMID- 29216427
TI  - A Novel Microemulsion Phase Transition: Toward the Elucidation of Third-Phase
      Formation in Spent Nuclear Fuel Reprocessing.
AB  - We present evidence that the transition between organic and third phases, which
      can be observed in the plutonium uranium reduction extraction (PUREX) process at
      high metal loading, is an unusual transition between two isotropic bicontinuous
      microemulsion phases. As this system contains so many components, however, we
      have been seeking first to investigate the properties of a simpler system,
      namely, the related metal-free, quaternary water/n-dodecane/nitric acid/tributyl
      phosphate (TBP) system. This quaternary system has been shown to exhibit, under
      appropriate conditions, three coexisting phases: a light organic phase, an
      aqueous phase, and the so-called third phase. In the current work, we focused on
      the coexistence of the light organic phase with the third phase. Using Gibbs
      ensemble Monte Carlo (GEMC) simulations, we found coexistence of a phase rich in
      nitric acid and dilute in n-dodecane (the third phase) with a phase more dilute
      in nitric acid but rich in n-dodecane (the light organic phase). The compositions
      and densities of these two coexisting phases determined using the simulations
      were in good agreement with those determined experimentally. Because such systems
      are generally dense and the molecules involved are not simple, the particle
      exchange rate in their GEMC simulations can be rather low. To test whether a
      system having a composition between those of the observed third and organic
      phases is indeed unstable with respect to phase separation, we used the Bennett
      acceptance ratio method to calculate the Gibbs energies of the homogeneous phase
      and the weighted average of the two coexisting phases, where the compositions of
      these phases were taken both from experimental results and from the results of
      the GEMC simulations. Both demixed states were determined to have statistically
      significant lower Gibbs energies than the uniform, mixed phase, providing
      confirmation that the GEMC simulations correctly predicted the phase separation.
      Snapshots from the simulations and a cluster analysis of the organic and third
      phases revealed structures akin to bicontinuous microemulsion phases, with the
      polar species residing within a mesh and with the surface of the mesh formed by
      amphiphilic TBP molecules. The nonpolar n-dodecane molecules were observed in
      these snapshots to be outside this mesh. The only large-scale structural
      differences observed between the two phases were the dimensions of the mesh.
      Evidence for the correctness of these structures was provided by the results of
      small-angle X-ray scattering (SAXS) studies, where the profiles obtained for both
      the organic and third phases agreed well with those calculated from simulations.
      Finally, we looked at the microscopic structures of the two phases. In the
      organic phase, the basic motif was observed to be one nitric acid molecule
      hydrogen-bonded to a TBP molecule. In the third phase, the most common structure
      was that of the hydrogen-bonded TBP-HNO3-HNO3 chain. A cluster analysis provided
      evidence for TBP forming an extended, connected network in both phases. Studies
      of the effects of metal ions on these systems will be presented elsewhere.

PMID- 29216428
TI  - Strong Electronic Coupling of Molecular Sites to Graphitic Electrodes via
      Pyrazine Conjugation.
AB  - Glassy carbon electrodes were functionalized with redox-active moieties by
      condensation of o-phenylenediamine derivatives with o-quinone sites native to
      graphitic carbon surfaces. Electrochemical and spectroscopic investigations
      establish that these graphite-conjugated catalysts (GCCs) exhibit strong
      electronic coupling to the electrode, leading to electron transfer (ET) behavior
      that diverges fundamentally from that of solution-phase or surface-tethered
      analogues. We find that (1) ET is not observed between the electrode and a redox
      active GCC moiety regardless of applied potential. (2) ET is observed at GCCs
      only if the interfacial reaction is ion-coupled. (3) Even when ET is observed,
      the oxidation state of a transition metal GCC site remains unchanged. From these
      observations, we construct a mechanistic model for GCC sites in which ET behavior
      is identical to that of catalytically active metal surfaces rather than to that
      of molecules in solution. These results suggest that GCCs provide a versatile
      platform for bridging molecular and heterogeneous electrocatalysis.

PMID- 29216429
TI  - Insights into the Chemical Mechanism for CO2(aq) and H+ in Aqueous Diamine
      Solutions - An Experimental Stopped-Flow Kinetic and 1H/13C NMR Study of Aqueous
      Solutions of N,N-Dimethylethylenediamine for Postcombustion CO2 Capture.
AB  - In an effort to advance the understanding of multiamine based CO2 capture process
      absorbents, we report here the determination of the kinetic and equilibrium
      constants for a simple linear diamine N,N-dimethylethylenediamine (DMEDA) via
      stopped-flow spectrophotometric kinetic measurements and 1H/13C NMR titrations at
      25.0  degrees C. From the kinetic data, the formation of monocarbamic acid
      (DMEDACOOH) from the reaction of DMEDA with CO2(aq) is the dominant reaction at
      high pH > 9.0 (k7 = 6.99 * 103 M-1.s-1). Below this pH, the formation of
      protonated monocarbamic acid (DMEDACOOH2) via the pathway involving DMEDAH+ and
      CO2(aq) becomes active and contributes to the kinetics despite the 107-fold
      decrease in the rate constant between the two pathways. 1H and 13C NMR spectra as
      a function of decreasing pH (increasing HCl concentration) at 25.0  degrees C
      have been evaluated here to confirm the protonation events in DMEDA. Calculations
      of the respective DMEDA nitrogen partial charges have also been undertaken to
      support the NMR protonation study. A comparison of the DMEDA kinetic constants
      with the corresponding data for piperazine (PZ) reveals that despite the larger
      basicity of DMEDA, the enhanced and superior kinetic performance of PZ with
      CO2(aq) above its predicted Bronsted reactivity is not observed in DMEDA.

PMID- 29216430
TI  - Nickel Nanoparticle Encapsulated in Few-Layer Nitrogen-Doped Graphene Supported
      by Nitrogen-Doped Graphite Sheets as a High-Performance Electromagnetic Wave
      Absorbing Material.
AB  - Herein we develop a facile strategy for fabricating nickel particle encapsulated
      in few-layer nitrogen-doped graphene supported by graphite carbon sheets as a
      high-performance electromagnetic wave (EMW) absorbing material. The obtained
      material exhibits sheetlike morphology with a lateral length ranging from a
      hundred nanometers to 2 MUm and a thickness of about 23 nm. Nickel nanoparticles
      with a diameter of approximately 20 nm were encapsulated in about six layers of
      nitrogen-doped graphene. As applied for electromagnetic absorbing material, the
      heteronanostructures exhibit excellent electromagnetic wave absorption property,
      comparable to most EMW absorbing materials previously reported. Typically, the
      effective absorption bandwidth (the frequency region falls within the reflection
      loss below -10 dB) is up to 8.5 GHz at the thicknesses of 3.0 mm for the
      heteronanostructures with the optimized Ni content. Furthermore, two processes,
      carbonization at a high temperature and subsequent treatment in hot acid
      solution, were involved in the preparation of the heteronanostructures, and thus,
      mass production was achieved easily, facilitating their practical applications.

PMID- 29216431
TI  - Photochemistry of Acetohydroxamic Acid in Solid Argon. FTIR and Theoretical
      Studies.
AB  - The products formed during exposure of the CH3CONHOH/Ar (AHA/Ar) matrices to the
      full output of the Xe lamp and to 225 nm OPO radiation are studied. The
      irradiation promotes the isomerization, 1Z -> 1E, and AHA photodissociation
      reactions. Four pairs of coproducts are experimentally found to appear in the
      photolysis, they form the complexes: CH3OH...HNCO (1), H2O...CH3NCO (2),
      H2O...CH3CNO (3) and CO...CH3NHOH (4). The structures of the complexes were
      optimized at the MP2 computational level with the 6-311++G(2d,2p) and aug-cc-pVTZ
      basis sets. Three local minima were predicted for the complex (1), two for the
      complexes (2) and (3) and four local minima were found for the complex (4). The
      comparison of the theoretical spectra with the experimental ones allowed us to
      determine the structures of the complexes formed in the matrix. The mechanisms of
      the reaction channels leading to formation of the four coproducts are proposed.
      It is concluded that the first step in formation of the (1), (2) and (3)
      complexes is the scission of the N-O bond whereas the creation of the complex (4)
      is due to the cleavage of the C-N bond.

PMID- 29216432
TI  - Mapping the Coulomb Environment in Interference-Quenched Ballistic Nanowires.
AB  - The conductance of semiconductor nanowires is strongly dependent on their
      electrostatic history because of the overwhelming influence of charged surface
      and interface states on electron confinement and scattering. We show that InAs
      nanowire field-effect transistor devices can be conditioned to suppress
      resonances that obscure quantized conduction thereby revealing as many as six sub
      bands in the conductance spectra as the Fermi-level is swept across the sub-band
      energies. The energy level spectra extracted from conductance, coupled with
      detailed modeling shows the significance of the interface state charge
      distribution revealing the Coulomb landscape of the nanowire device. Inclusion of
      self-consistent Coulomb potentials, the measured geometrical shape of the
      nanowire, the gate geometry and nonparabolicity of the conduction band provide a
      quantitative and accurate description of the confinement potential and resulting
      energy level structure. Surfaces of the nanowire terminated by HfO2 are shown to
      have their interface donor density reduced by a factor of 30 signifying the
      passivating role played by HfO2.

PMID- 29216433
TI  - Aging, Jamming, and the Limits of Stability of Amorphous Solids.
AB  - Apart from not having crystallized, supercooled liquids can be considered as
      being properly equilibrated and thus can be described by a few thermodynamic
      control variables. In contrast, glasses and other amorphous solids can be
      arbitrarily far away from equilibrium and require a description of the history of
      the conditions under which they formed. In this paper we describe how the
      locality of interactions intrinsic to finite-dimensional systems affects the
      stability of amorphous solids far off equilibrium. Our analysis encompasses both
      structural glasses formed by cooling and colloidal assemblies formed by
      compression. A diagram outlining regions of marginal stability can be adduced
      which bears some resemblance to the quasi-equilibrium replica meanfield theory
      phase diagram of hard sphere glasses in high dimensions but is distinct from that
      construct in that the diagram describes not true phase transitions but kinetic
      transitions that depend on the preparation protocol. The diagram exhibits two
      distinct sectors. One sector corresponds to amorphous states with relatively open
      structures, the other to high density, more closely packed ones. The former
      transform rapidly owing to there being motions with no free energy barriers;
      these motions are string-like locally. In the dense region, amorphous systems age
      via compact activated reconfigurations. The two regimes correspond, in
      equilibrium, to the collisional or uniform liquid and the so-called landscape
      regime, respectively. These are separated by a spinodal line of dynamical
      crossovers. Owing to the rigidity of the surrounding matrix in the landscape,
      high-density part of the diagram, a sufficiently rapid pressure quench adds
      compressive energy which also leads to an instability toward string-like motions
      with near vanishing barriers. Conversely, a dilute collection of rigid particles,
      such as a colloidal suspension leads, when compressed, to a spatially
      heterogeneous structure with percolated mechanically stable regions. This jamming
      corresponds to the onset of activation when the spinodal line is traversed from
      the low density side. We argue that a stable glass made of sufficiently rigid
      particles can also be viewed as exhibiting sporadic and localized buckling
      instabilities that result in local jammed structures. The lines of instability we
      discuss resemble the Gardner transition of meanfield systems but, in contrast, do
      not result in true criticality owing to being short-circuited by activated
      events. The locally marginally stable modes of motion in amorphous solids
      correspond to secondary relaxation processes in structural glasses. Their
      relevance to the low temperature anomalies in glasses is also discussed.

PMID- 29216435
TI  - Dysregulated Systemic Inflammation Favors Bacterial Growth and Development of
      Nosocomial Infections.

PMID- 29216434
TI  - Yale Integrative Medicine Leader, Ather Ali, ND, MPH, MHS (1975-2017).

PMID- 29216436
TI  - Altered muscarinic receptor expression in the cerebral cortex of epileptic rats:
      restorative role of Withania somnifera.
AB  - Temporal lobe epilepsy involves a sequence of events that can lead to
      neurotransmitter signalling alterations. There are many herbal extracts
      considered to be alternative therapeutic methods to manage epilepsy. In this
      study, we investigated the effect of Withania somnifera (WS) root extract and
      withanolide A (WA) in the management of temporal lobe epilepsy. Confocal imaging
      of TOPRO-3-stained cortical sections showed severe damage in the epileptic brain.
      We also observed a reduced antioxidant potential and increased peroxide levels in
      the epileptic test group of rats. Oxidative stress resulted in the down
      regulation of CREB, NF-kappaB, and TNF-alpha, and with up-regulation of the
      apoptotic factors caspases 8 and 3 and Bax in the epileptic group. Epileptic
      condition also resulted in increased muscarinic receptor binding and mRNA
      expression in the cerebral cortex. Withania somnifera and withanolide A
      significantly reversed the altered muscarinic receptor expression and reversed
      the oxidative stress and resultant derailment in cell signalling. Thus our
      studies suggest that Withania somnifera and withanolide A play important roles in
      central muscarinic receptor functional balance and activation of the antioxidant
      system in the cerebral cortex in temporal lobe epilepsy. These findings can be of
      immense therapeutic significance for managing epilepsy.

PMID- 29216437
TI  - Erythropoietin-Producing Hepatoma Receptor Tyrosine Kinase A2 Modulation
      Associates with Protective Effect of Prone Position in Ventilator-induced Lung
      Injury.
AB  - The erythropoietin-producing hepatoma (Eph) receptor tyrosine kinase A2 (EphA2)
      and its ligand, ephrinA1, play a pivotal role in inflammation and tissue injury
      by modulating the epithelial and endothelial barrier integrity. Therefore, EphA2
      receptor may be a potential therapeutic target for modulating ventilator-induced
      lung injury (VILI). To support this hypothesis, here, we analyzed EphA2/ephrinA1
      signaling in the process of VILI and determined the role of EphA2/ephrinA1
      signaling in the protective mechanism of prone positioning in a VILI model. Wild
      type mice were ventilated with high (24 ml/kg; positive end-expiratory pressure,
      0 cm; 5 h) tidal volume in a supine or prone position. Anti-EphA2 receptor
      antibody or IgG was administered to the supine position group. Injury was
      assessed by analyzing the BAL fluid, lung injury scoring, and transmission
      electron microscopy. Lung lysates were evaluated using cytokine/chemokine ELISA
      and Western blotting of EphA2, ephrinA1, PI3Kgamma, Akt, NF-kappaB, and P70S6
      kinase. EphA2/ephrinA1 expression was higher in the supine high tidal volume
      group than in the control group, but it did not increase upon prone positioning
      or anti-EphA2 receptor antibody treatment. EphA2 antagonism reduced the extent of
      VILI and downregulated the expression of PI3Kgamma, Akt, NF-kappaB, and P70S6
      kinase. These findings demonstrate that EphA2/ephrinA1 signaling is involved in
      the molecular mechanism of VILI and that modulation of EphA2/ehprinA1 signaling
      by prone position or EphA2 antagonism may be associated with the lung-protective
      effect. Our data provide evidence for EphA2/ehprinA1 as a promising therapeutic
      target for modulating VILI.

PMID- 29216438
TI  - Antiulcerative Activity of Milk Proteins Hydrolysates.
AB  - Several studies have shown the protective effect of dairy products, especially
      alpha-lactalbumin and derived hydrolysates, against induced gastric ulcerative
      lesions. The mucus strengthening represents an important mechanism in the defense
      of gastrointestinal mucosa. Previously, a hydrolysate from casein (CNH) and a
      hydrolysate from whey protein concentrate rich in beta-lactoglobulin (WPH)
      demonstrated a stimulatory activity on mucus production in intestinal goblet
      cells. The aim of this work was to evaluate the possible antiulcerative activity
      of these two hydrolysates in an ethanol-induced ulcer model in rats. All tested
      samples significantly reduced the ulcerative lesions index (ULI), compared with
      the saline solution, using doses of 300 and 1000 mg kg-1 body weight with
      decreases up to 66.3% ULI. A dose-response relationship was found for both
      hydrolysates. The involvement of endogenous sulfhydryl (SH) groups and
      prostaglandins (PGs) in the antiulcerative activity was evaluated using their
      blockage. The antiulcerative activity of WPH showed a drastic decrease in
      presence of N-ethylmaleimide (from 41.4% to 9.2% ULI). However, the CNH
      antiulcerative properties were not significantly affected. The cytoprotective
      effect of WPH appears to depend on a PG-mediated mechanism. In conclusion, CNH
      and WPH demonstrated in vivo antiulcerative properties and represent a promising
      alternative as protectors of the gastric mucosa.

PMID- 29216440
TI  - An Interdisciplinary Approach to Implementing a Best Practice Guideline in Public
      Health.
AB  - This article describes how one Ontario Public Health Unit implemented a best
      practice guideline throughout the organization and across disciplines to achieve
      best practice outcomes in the delivery of client-centered care. Integration of
      evidence-informed practice presents challenges for both implementation and
      sustainability. Applying a best practice guideline in the public health setting
      can add to the challenge. To address this, a variety of interventions were
      applied: building an interdisciplinary team, adapting a Registered Nurses'
      Association of Ontario Best Practice Guideline to reflect public health practice
      for nursing and other disciplines, developing a working definition of "client,"
      engaging staff in knowledge translation, developing policy to support practice
      change, and incorporating client-centered care principles into daily practice.
      Outcomes indicate that nursing best practice guidelines, specific to client
      centered care, can be successfully adapted and applied in public health practice.
      Considerations include the varied definitions of a "client," the various roles of
      public health professionals, and engagement of both internal and external
      clients. Moreover, interdisciplinary staff can apply the principles of client
      centered care when working with clients and when engaging in education-, practice
      , and policy-level initiatives to support evidence-informed practice.

PMID- 29216439
TI  - Gender Differences in Social Cognition: A Cross-Sectional Pilot Study of Recently
      Diagnosed Patients with Schizophrenia and Healthy Subjects.
AB  - OBJECTIVES: This study had 2 objectives: First, to explore the gender-related
      differences in emotional processing (EP) and theory of mind-both cognitive (CToM)
      and affective (AToM)-in patients with schizophrenia and in a control group of
      healthy subjects; and, second, to examine, from a gender perspective, the
      possible association between EP and CToM in the AToM performance. METHODS: Forty
      patients with schizophrenia/schizoaffective disorder were recruited and matched
      by gender, age and years of education with 40 healthy subjects. EP was measured
      by the pictures of facial affect (POFA) test. CToM was measured using first- and
      second-order false-belief (FB) stories. AToM was measured by the reading the mind
      in the eyes test (RMET). Group and gender differences in CToM were analysed using
      the X2 test, whereas EP and AToM were analysed using the non-parametric Mann
      Whitney U Test and a general linear model. Results were adjusted by intelligence
      quotient and negative symptomatology. RESULTS: Patients with schizophrenia
      underperformed against healthy subjects in the POFA test, second-order FB, and
      RMET, but not in first-order FB. No significant gender differences were found.
      However, there was a trend showing that females outperformed males in the POFA (
      P = 0.056). Group ( P < 0.001), POFA ( P < 0.001) and second-order FB ( P =
      0.022) were the best factors predicting RMET performance (adjusted R2 = 0.584).
      CONCLUSIONS: Our results suggest that the illness is the main factor related to
      the deficit in social cognition, except for the basic aspects of the CToM that
      were unimpaired in most patients. Nevertheless, the influence of female gender in
      EP should not be neglected in any group. Finally, the hierarchal interaction
      between these domains is discussed.

PMID- 29216441
TI  - Change in Sense of Nondual Awareness and Spiritual Awakening in Response to a
      Multidimensional Well-Being Program.
AB  - OBJECTIVE: This study examined the effects of a comprehensive mind-body program
      on sense of nondual awareness and spiritual awakening. DESIGN AND INTERVENTION:
      The study compared the effects of participation in an intensive 6-day Ayurveda
      based mind-body program that addressed physical, emotional, and spiritual domains
      as compared with a control condition. SETTING: Resort setting. SUBJECTS:
      Participants were 69 healthy women and men (mean age 53.9 years; range 32-86).
      OUTCOME MEASURE: The primary outcome was the Nondual Embodiment Thematic
      Inventory (NETI). RESULTS: A significant group by time interaction (p = 0.029)
      indicated that after the intervention, participants in the mind-body program
      showed a significant increase in NETI scores (p < 0.03), which was sustained 1
      month later (p < 0.01). CONCLUSION: Findings suggest that an intensive program
      providing holistic instruction and experience in mind-body practices can lead to
      a significant and sustained shift in perception of self-awareness, one that is
      likely favorable to well-being.

PMID- 29216442
TI  - Lycopene depresses glutamate release through inhibition of voltage-dependent Ca2+
      entry and protein kinase C in rat cerebrocortical nerve terminals.
AB  - Lycopene is a natural dietary carotenoid that was reported to exhibit a
      neuroprotective profile. Considering that excitotoxicity and cell death induced
      by glutamate are involved in many brain disorders, the effect of lycopene on
      glutamate release in rat cerebrocortical nerve terminals and the possible
      mechanism involved in such effect was investigated. We observed here that
      lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and
      intrasynaptosomal Ca2+ concentration elevation. The inhibitory effect of lycopene
      on 4-AP-evoked glutamate release was markedly reduced in the presence of the
      Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker omega-conotoxin MVIIC, but
      was insensitive to the intracellular Ca2+-release inhibitors dantrolene and
      CGP37157. Furthermore, in the presence of the protein kinase C inhibitors
      GF109203X and Go6976, the action of lycopene on evoked glutamate release was
      prevented. These results are the first to suggest that lycopene inhibits
      glutamate release from rat cortical synaptosomes by suppressing presynaptic Ca2+
      entry and protein kinase C activity.

PMID- 29216443
TI  - Genetic classification of Aegilops columnaris Zhuk. (2n=4x=28, UcUcXcXc)
      chromosomes based on FISH analysis and substitution patterns in common wheat *
      Ae. columnaris introgressive lines.
AB  - Aegilops columnaris is a tetraploid species originated from Ae. umbellulata
      (2n=2x=14, UU) and a yet unknown diploid grass species. Although Ae. columnaris
      possesses some agronomically valuable traits, such as heat and drought tolerance
      and resistance to pests, it has never been used in wheat breeding because of
      difficulties in producing hybrids and a lack of information on the relationships
      between Ae. columnaris and common wheat chromosomes. In this paper, we report the
      development of 57 wheat - Ae. columnaris introgressive lines covering 8 of the14
      chromosomes of Aegilops. Based on substitution spectra of hybrids and the results
      of FISH analysis of the parental Ae. columnaris line with seven DNA probes, we
      have developed the genetic nomenclature of the Uc and Xc chromosomes. Genetic
      groups and genome affinities were established for 11 of 14 chromosomes; the
      classification of the remaining three chromosomes remains unsolved. Each Ae.
      columnaris chromosome was characterized on the basis of C-banding pattern and the
      distribution of seven DNA sequences. Introgression processes were shown to depend
      on the parental wheat genotype and the level of divergence of homoeologous
      chromosomes. We found that lines carrying chromosome 5Xc are resistant to leaf
      rust; therefore, this chromosome could possess novel resistance genes that have
      never been utilized in wheat breeding.

PMID- 29216444
TI  - Under Pressure to Clarify Pulmonary Hypertension Clinical Risk.

PMID- 29216445
TI  - Home-based Approach Noninferior to Hospital-based Approach in Managing Patients
      with Suspected Obstructive Sleep Apnea Syndrome.

PMID- 29216447
TI  - Expectations about recipients' prosociality and mental time travel relate to
      resource allocation in preschoolers.
AB  - Previous studies have revealed that preschoolers selectively allocate their
      resources based on their social relationship with recipients such as friendship.
      In this investigation, we investigated how expectations about recipients'
      prosociality and the ability of future thinking relate to the selective
      allocation of resources. In Study 1, participants aged 3.5-6 years chose how to
      allocate resources from two ways (selfish allocation, where only the participants
      could receive stickers, and equal allocation, where the participants and
      recipients receive get the same number of stickers) in costly and non-costly
      situations with three recipients (friend, peer, and stranger). Participants were
      asked to state which alternatives the recipients would choose if they were given
      a choice. The results showed that children aged 5 and 6 years tended to choose
      equal allocation of resources when they expected the recipients to do the same
      both in costly and non-costly situations. This tendency was not observed in
      children aged 3.5 and 4 years. In Study 2, the relationships between selectivity
      in non-costly allocation and two facets of future thinking (delay of
      gratification and mental time travel) were investigated in children aged 5 and 6
      years. The results suggested that children with a higher mental time travel
      ability tended to be more selective in allocating resources based on social
      relationships; they tended to allocate more resources to the friend and fewer to
      the peer. Our findings suggest that expectations about a recipient's prosociality
      and the ability of mental time travel affect selectivity of resource allocation
      in children aged 5 and 6 years.

PMID- 29216446
TI  - Comparison of 2 weekly-equalized volume resistance-training routines using
      different frequencies on body composition and performance in trained males.
AB  - The present study compared the effects of 2 weekly-equalized volume and relative
      load interventions on body composition, strength, and power. Based on individual
      baseline maximal strength values, 18 recreationally trained men were pair-matched
      and consequently randomly assigned to one of the following experimental groups: a
      low volume per session with a high frequency (LV-HF, n = 9) group who trained for
      4 days (Mondays, Tuesdays, Thursdays, and Fridays) or a high volume per session
      and low frequency (HV-LF, n = 9) group who trained for 2 days (Mondays and
      Thursdays). Both groups performed 2 different routines over 6 weeks. Participants
      were tested pre- and post- intervention for maximal strength, upper body power,
      fat-free mass, limb circumferences, and muscle thickness. Compared with baseline
      values, both groups increased their fat-free mass (HV-LF: +1.19 +/- 1.94; LV-HF:
      +1.36 +/- 1.06 kg, p < 0.05) and vastus medialis thickness (HV-LF: +2.18 +/-
      1.88, p < 0.01; LV-HF: +1.82 +/- 2.43 mm, p < 0.05), but only the HV-LF group
      enhanced arm circumference (1.08 +/- 1.47 cm, p < 0.05) and elbow flexors
      thickness (2.21 +/- 2.81 mm, P < 0.01) values and decreased their fat mass (-2.41
      +/- 1.10, P < 0.01). Both groups improved (p < 0.01) the maximal loads lifted in
      the bench press (LV-HF: +0.14 +/- 0.01; HV-LF: +0.14 +/- 0.01 kg.body mass-1) and
      the squat (LV-HF: +0.14 +/- 0.06; HV-LF: 0.17 +/- 0.01 kg.body mass-1) exercises
      as well as in upper body power (LV-HF: +0.22 +/- 0.25; HV-LF: +0.27 +/- 0.22
      W.body mass-1) Although both training strategies improved performance and lower
      body muscle mass, only the HV-LF protocol increased upper body hypertrophy and
      improved body composition.

PMID- 29216448
TI  - Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a
      Model of beta-amyloidosis.
AB  - The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late
      onset Alzheimer disease. Previous studies suggest that reduction of apoE levels
      through genetic manipulation can reduce Abeta pathology. However, it is not clear
      how reduction of apoE levels after birth would affect amyloid deposition. We
      utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the
      brains of APP/PS1-21 mice homozygous for the APOE-epsilon4 or APOE-epsilon3
      allele. ASO treatment starting after birth led to a significant decrease in Abeta
      pathology when assessed at 4 months. Interestingly, ASO treatment starting at the
      onset of amyloid deposition led to an increase in Abeta plaque size and a
      reduction in plaque-associated neuritic dystrophy with no change in overall
      plaque load. These results suggest that lowering apoE levels prior to plaque
      deposition can strongly affect the initiation of Abeta pathology while lowering
      apoE after Abeta seeding modulates plaque size and toxicity.

PMID- 29216449
TI  - ApoE4 Accelerates Early Seeding of Amyloid Pathology.
AB  - Accumulation and aggregation of amyloid-beta (Abeta) in the brain is an
      initiating step in the pathogenesis of Alzheimer's disease (AD). The epsilon4
      allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for
      late-onset AD. Although there is strong evidence showing that apoE4 enhances
      amyloid pathology, it is not clear what the critical stage(s) is during amyloid
      development in which apoE4 has the strongest impact. Using apoE inducible mouse
      models, we show that increased expression of astrocytic apoE4, but not apoE3,
      during the seeding stage of amyloid development enhanced amyloid deposition and
      neuritic dystrophy in amyloid model mice. ApoE4, but not apoE3, significantly
      increased brain Abeta half-life measured by in vivo microdialysis. Furthermore,
      apoE4 expression increased whereas apoE3 reduced amyloid-related gliosis in the
      mouse brains. Together, our results demonstrate that apoE4 has the greatest
      impact on amyloid during the seeding stage, likely by perturbing Abeta clearance
      and enhancing Abeta aggregation.

PMID- 29216451
TI  - Mechanosensory-Based Phase Coding of Odor Identity in the Olfactory Bulb.
AB  - Mitral and tufted (M/T) cells in the olfactory bulb produce rich temporal
      patterns of activity in response to different odors. However, it remains unknown
      how these temporal patterns are generated and how they are utilized in olfaction.
      Here we show that temporal patterning effectively discriminates between the two
      sensory modalities detected by olfactory sensory neurons (OSNs): odor and airflow
      driven mechanical signals. Sniff-induced mechanosensation generates glomerulus
      specific oscillatory activity in M/T cells, whose phase was invariant across
      airflow speed. In contrast, odor stimulation caused phase shifts (phase coding).
      We also found that odor-evoked phase shifts are concentration invariant and
      stable across multiple sniff cycles, contrary to the labile nature of rate
      coding. The loss of oscillatory mechanosensation impaired the precision and
      stability of phase coding, demonstrating its role in olfaction. We propose that
      phase, not rate, coding is a robust encoding strategy of odor identity and is
      ensured by airflow-induced mechanosensation in OSNs.

PMID- 29216452
TI  - DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1
      during Mitosis.

PMID- 29216453
TI  - A Sensorimotor Circuit in Mouse Cortex for Visual Flow Predictions.

PMID- 29216450
TI  - Endocannabinoid Actions on Cortical Terminals Orchestrate Local Modulation of
      Dopamine Release in the Nucleus Accumbens.
AB  - Dopamine (DA) transmission mediates numerous aspects of behavior. Although DA
      release is strongly linked to firing of DA neurons, recent developments indicate
      the importance of presynaptic modulation at striatal dopaminergic terminals. The
      endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper
      of goal-directed behavior. Here we report that extracellular DA increases induced
      by selective optogenetic activation of cholinergic neurons in the nucleus
      accumbens (NAc) are inhibited by CB1 agonists and eCBs. This modulation requires
      CB1 receptors on cortical glutamatergic afferents. Dopamine increases driven by
      optogenetic activation of prefrontal cortex (PFC) terminals in the NAc are
      similarly modulated by activation of these CB1 receptors. We further demonstrate
      that this same population of CB1 receptors modulates optical self-stimulation
      sustained by activation of PFC afferents in the NAc. These results establish
      local eCB actions on PFC terminals within the NAc that inhibit mesolimbic DA
      release and constrain reward-driven behavior.

PMID- 29216454
TI  - Fibrinogen in the Nervous System: Glia Beware.
AB  - Re-myelination of CNS nerves after injury is ineffective. Here, Petersen et al.
      (2017) show that the blood clotting protein fibrinogen inhibits nerve repair by
      preventing oligodendrocyte progenitor cells from differentiating into myelinating
      oligodendrocytes. Targeting fibrinogen or its downstream BMP signaling pathway
      may help with CNS repair.

PMID- 29216455
TI  - Seeds of Destruction: New Mechanistic Insights into the Role of Apolipoprotein E4
      in Alzheimer's Disease.
AB  - Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer's
      disease. Despite nearly 25 years of research, the mechanism by which apoE4
      confers increased risk for Alzheimer's disease remains enigmatic. In this issue
      of Neuron, Liu et al. (2017) and Huynh et al. (2017) shed new light on this
      important question.

PMID- 29216456
TI  - Homeostatic Scaling of AMPA Receptors by Semaphorin.
AB  - Regulation of AMPA receptors mediates homeostatic scaling. In this issue of
      Neuron, Wang et al. (2017) identify a new role of secreted semaphorin 3F and
      elucidate how it triggers synaptic downscaling of AMPA receptors through
      regulation of the binding of Sema3F holoreceptor complex to AMPA receptors.

PMID- 29216457
TI  - A Sing-Song Way of Vocalizing: Generalization and Specificity in Language and
      Birdsong.
AB  - Spoken languages such as German are extremely discrete, whereas others such as
      Portuguese are melodic or "sing-song" wherein identifying a word relies on what
      comes before and after. Perhaps surprisingly, birdsong also exhibits specificity
      and generalization as articulated by Tian and Brainard (2017).

PMID- 29216458
TI  - A Commitment to Open Source in Neuroscience.
AB  - Modern neuroscience increasingly relies on custom-developed software, but much of
      this is not being made available to the wider community. A group of researchers
      are pledging to make code they produce for data analysis and modeling open
      source, and are actively encouraging their colleagues to follow suit.

PMID- 29216459
TI  - Pushing the Boundaries of Neuroimaging with Optoacoustics.
AB  - With the central ability to visualize a variety of endogenous chromophores and
      biomarkers or exogenous contrast agents, optoacoustic (photoacoustic) imaging
      empowers new experimental capabilities for investigating brain mechanisms and
      functions. Here, the operational principles of optoacoustic neuroimaging are
      reviewed in conjunction with recent advances enabling high-resolution and real
      time observation, which extend beyond the reach of optical imaging methods.
      Multiple implementations of optoacoustics for monitoring hemodynamics and neuro
      vascular responses in the brain are showcased. The unique capabilities of
      optoacoustic imaging for multi-spectral cellular and molecular sensing are
      discussed with reference to recent application for visualizing healthy and
      diseased brains. Outstanding challenges in the field are considered in the
      context of current and future applications of optoacoustic neuroimaging for basic
      and translational neuroscience research. In pushing the boundaries of brain
      imaging, optoacoustic methods afford major insights into the neuronal mechanisms
      of brain functions and organization of behavior.

PMID- 29216460
TI  - Getting a Handle on Neuropharmacology by Targeting Receptor-Associated Proteins.
AB  - Targeted therapy for neuropsychiatric disorders requires selective modulation of
      dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically
      have associated proteins discretely expressed in specific neuronal pathways;
      these accessory proteins provide a new dimension for drug discovery. Recent
      studies show that targeting a TARP auxiliary subunit of AMPA receptors
      selectively modulates neuronal excitability in specific forebrain pathways
      relevant to epilepsy. Other medicinally important ion channels, gated by
      glutamate, gamma-aminobutyric acid (GABA), and acetylcholine, also have
      associated proteins, which may be druggable. This emerging pharmacology of
      receptor-associated proteins provides a new approach for improving drug efficacy
      while mitigating side effects.

PMID- 29216461
TI  - Associations of environmental exposure to metals with the risk of hypertension in
      China.
AB  - Hypertension contributes largely to the global burden of disease and mortality.
      Environmental exposure to metals might be a causative factor for hypertension,
      but the association remains unclear. The present case-control study of 502
      hypertension patients and 502 healthy participants aimed to evaluate the
      potential relationships between the concentrations of 20 metal in urine and the
      risk of hypertension in a Chinese population. Multivariate logistic analyses
      adjusted for potential confounders were performed separately considering the
      effects of single and multi-metal. We found the increasing trends of urinary Fe,
      Co, Ni, Cu, Zn and Sr quartiles and the decreasing trends of urinary V and Rb
      quartiles with the ORs for hypertension. These dose-response associations were
      confirmed in the RCS models and remained robust in the multi-metal model. Urinary
      Hg quartiles were positively associated with the risk of hypertension in the
      models of single-metal and multi-metal. Urinary Cd quartiles were inversely
      associated with the risk of hypertension in the multi-metal model. Besides,
      modification effects of gender, BMI and smoking status on the associations of the
      exposure to various metals with the risk of hypertension were also suggested in
      the subgroup analysis. Our findings suggest that environmental exposure to V, Fe,
      Co, Ni, Cu, Zn, Rb, Sr, Cd and Hg might be related with the prevalence of
      hypertension. Further studies with prospective design should be conducted to
      confirm these findings.

PMID- 29216462
TI  - Soil moisture and texture primarily control the soil nutrient stoichiometry
      across the Tibetan grassland.
AB  - Soil nutrient stoichiometry and its environmental controllers play vital roles in
      understanding soil-plant interaction and nutrient cycling under a changing
      environment, while they remain poorly understood in alpine grassland due to lack
      of systematic field investigations. We examined the patterns and controls of soil
      nutrients stoichiometry for the top 10cm soils across the Tibetan ecosystems.
      Soil nutrient stoichiometry varied substantially among vegetation types. Alpine
      swamp meadow had larger topsoil C:N, C:P, N:P, and C:K ratios compared to the
      alpine meadow, alpine steppe, and alpine desert. In addition, the presence or
      absence of permafrost did not significantly impact soil nutrient stoichiometry in
      Tibetan grassland. Moreover, clay and silt contents explained approximately 32.5%
      of the total variation in soil C:N ratio. Climate, topography, soil properties,
      and vegetation combined to explain 10.3-13.2% for the stoichiometry of soil C:P,
      N:P, and C:K. Furthermore, soil C and N were weakly related to P and K in alpine
      grassland. These results indicated that the nutrient limitation in alpine
      ecosystem might shifts from N-limited to P-limited or K-limited due to the
      increase of N deposition and decrease of soil P and K contents under the changing
      climate conditions and weathering stages. Finally, we suggested that soil
      moisture and mud content could be good predictors of topsoil nutrient
      stoichiometry in Tibetan grassland.

PMID- 29216463
TI  - Application of double-focusing sector field ICP-MS for determination of
      ultratrace constituents in samples characterized by complex composition of the
      matrix.
AB  - The performance of double focusing, sector field mass spectrometry (ICP-SFMS) for
      determination of analytes, including technology critical elements (TCE), at ultra
      trace levels in environmental and clinical matrices was critically evaluated.
      Different configurations of the ICP-SFMS introduction system as well as various
      sample preparations, pre-concentration and matrix separation methods were
      employed and compared. Factors affecting detection capabilities and accuracy of
      data produced (instrumental sensitivity, contamination risks, purity of reagents,
      spectral interferences, matrix effects, analyte recovery and losses) were
      discussed. Optimized matrix-specific methods were applied to a range of reference
      and control materials (riverine, brackish and seawaters; whole blood, serum and
      urine) as well as tap water and snow samples collected in the area of Lulea city,
      northern Sweden; brackish and seawater from the Laptev Sea; venous blood samples
      with a special emphasis on determination of Au, Ag, Ir, Os, Pd, Pt, Re, Rh, Ru,
      Sb and Te. Even though these low abundant elements are relatively under
      documented, the results produced were compared with published data, where
      available.

PMID- 29216464
TI  - Traffic pollutants measured inside vehicles waiting in line at a major US-Mexico
      Port of Entry.
AB  - At US-Mexico border Ports of Entry, vehicles idle for long times waiting to cross
      northbound into the US. Long wait times at the border have mainly been studied as
      an economic issue, however, exposures to emissions from idling vehicles can also
      present an exposure risk. Here we present the first data on in-vehicle exposures
      to driver and passengers crossing the US-Mexico border at the San Ysidro,
      California Port of Entry (SYPOE). Participants were recruited who regularly
      commuted across the border in either direction and told to drive a scripted route
      between two border universities, one in the US and one in Mexico. Instruments
      were placed in participants' cars prior to commute to monitor-1-minute average
      levels of the traffic pollutants ultrafine particles (UFP), black carbon (BC) and
      carbon monoxide (CO) in the breathing zone of drivers and passengers. Location
      was determined by a GPS monitor. Results reported here are for 68 northbound
      participant trips. The highest median levels of in-vehicle UFP were recorded
      during the wait to cross at the SYPOE (median 29,692particles/cm3) significantly
      higher than the portion of the commute in the US (median 20,508particles/cm3)
      though not that portion in Mexico (median 22, 191particles/cm3). In-vehicle BC
      levels at the border were significantly lower than in other parts of the commute.
      Our results indicate that waiting in line at the SYPOE contributes a median 62.5%
      (range 15.5%-86.0%) of a cross-border commuter's exposure to UFP and a median
      44.5% (range (10.6-79.7%) of exposure to BC inside the vehicle while traveling in
      the northbound direction. Reducing border wait time can significantly reduce in
      vehicle exposures to toxic air pollutants such as UFP and BC, and these
      preventable exposures can be considered an environmental justice issue.

PMID- 29216465
TI  - Optical source profiles of brown carbon in size-resolved particulate matter from
      typical domestic biofuel burning over Guanzhong Plain, China.
AB  - In this study, both PM2.5 and size-resolved source samples were collected from a
      "heated kang" and an advanced stove to investigate the optical properties of
      brown carbon (BrC). The light-absorption coefficient (babs), the absorption
      Angstrom exponent (AAE), and the mass absorption cross-section (MAC) of both
      water and methanol-extracted BrC were investigated. The methanol-extracted BrC
      (BrCmethanol) had higher light absorption than water-extracted BrC (BrCwater).
      The value of PM2.5 babs of BrCmethanol at 365nm (babs365,methanol) dramatically
      decreased from 64,669.8Mm-1 for straw burning in the "heated kang" to 1169.2Mm-1
      for maize straw briquettes burning in the advanced stove at the same burning
      rate. The value of PM2.5 MAC for BrCmethanol at 365nm (MAC365,methanol) decreased
      from 1.8m2g-1 in the "heated kang" to 1.3m2g-1 in the advanced stove. For
      smoldering burning in the "heated kang", babs365,methanol, MAC365,methanol, and
      K+ showed a unimodal distribution that peaked at sizes <0.4MUm. However, the
      babs365,methanol and MAC365,methanol size distributions of the briquette burning
      in the advanced stove showed a bimodal pattern, with a large peak at sizes
      <0.4MUm and a minor peak in the size range of 4.7-5.8MUm. The babs365,methanol
      value for sizes <0.4MUm (277.4Mm-1) was only 12.3% compared to those obtained
      from the "heated kang". The burning rate did not influence the size distribution
      pattern of either the "heated kang" or the advanced stove. Results from a
      radiative model show that biomass burning is an important factor for light
      absorptivity, and the use of an advanced stove can reduce the simple forcing
      efficiency value by nearly 20% in UV bands compared to the "heated kang". Our
      results indicate that changing the combustion style from maize straw smoldering
      to briquette burning in an advanced stove can effectively reduce BrC emissions
      during heating seasons in rural areas of Guanzhong Plain.

PMID- 29216466
TI  - The spatiotemporal transmission of dengue and its driving mechanism: A case study
      on the 2014 dengue outbreak in Guangdong, China.
AB  - Dengue transmission is a complex spatiotemporal process with hidden interactions
      between hosts, vectors, and viruses as well as environment. This study aims to
      identify the transmission patterns and the driving mechanism that contributed to
      the dengue epidemics occurred in Guangdong Province of China in 2014. Based on
      the city-specific epidemiological, meteorological, demographic and geographic
      data, we first performed wavelet analysis and then integrated the key dynamics
      (i.e., mosquito population dynamics, human movement, virus transmission, and
      parameter estimation) into a transmission model. Using these methods, we found a
      clear temporal sequence and correlation of dengue transmission between cities,
      and such relationship is associated with socioeconomic factors. We further
      obtained the specific component of dengue incidence data in each city, and
      presented the underlying infectivity networks for characterizing how dengue
      transmits from one location to another. The results showed that the communication
      of in-out infections with Guangzhou and Foshan could be responsible for the large
      scale diffusion of dengue epidemics in Guangdong in 2014. Our findings can offer
      new insights into how to improve the predictability and risk assessment of dengue
      transmission.

PMID- 29216467
TI  - Drivers of dissolved organic carbon export in a subarctic catchment: Importance
      of microbial decomposition, sorption-desorption, peatland and lateral flow.
AB  - Tundra soils account for 50% of global stocks of soil organic carbon (SOC), and
      it is expected that the amplified climate warming in high latitude could cause
      loss of this SOC through decomposition. Decomposed SOC could become
      hydrologically accessible, which increase downstream dissolved organic carbon
      (DOC) export and subsequent carbon release to the atmosphere, constituting a
      positive feedback to climate warming. However, DOC export is often neglected in
      ecosystem models. In this paper, we incorporate processes related to DOC
      production, mineralization, diffusion, sorption-desorption, and leaching into a
      customized arctic version of the dynamic ecosystem model LPJ-GUESS in order to
      mechanistically model catchment DOC export, and to link this flux to other
      ecosystem processes. The extended LPJ-GUESS is compared to observed DOC export at
      Stordalen catchment in northern Sweden. Vegetation communities include flood
      tolerant graminoids (Eriophorum) and Sphagnum moss, birch forest and dwarf shrub
      communities. The processes, sorption-desorption and microbial decomposition (DOC
      production and mineralization) are found to contribute most to the variance in
      DOC export based on a detailed variance-based Sobol sensitivity analysis (SA) at
      grid cell-level. Catchment-level SA shows that the highest mean DOC exports come
      from the Eriophorum peatland (fen). A comparison with observations shows that the
      model captures the seasonality of DOC fluxes. Two catchment simulations, one
      without water lateral routing and one without peatland processes, were compared
      with the catchment simulations with all processes. The comparison showed that the
      current implementation of catchment lateral flow and peatland processes in LPJ
      GUESS are essential to capture catchment-level DOC dynamics and indicate the
      model is at an appropriate level of complexity to represent the main mechanism of
      DOC dynamics in soils. The extended model provides a new tool to investigate
      potential interactions among climate change, vegetation dynamics, soil hydrology
      and DOC dynamics at both stand-alone to catchment scales.

PMID- 29216468
TI  - Determination of legacy and novel brominated flame retardants in dust from end of
      life office equipment and furniture from Pretoria, South Africa.
AB  - Indoor dust is known to be a source of human exposure to brominated flame
      retardants (BFRs) and these consists of the legacy polybrominated diphenyl ethers
      (PBDEs), total hexabromocyclododecane (T-HBCDD) and the "Novel or alternate"
      Brominated flame retardants (NBFRs). In this study, x-ray fluorescence (XRF)
      analyser was employed to measure elemental bromine contents in office furniture
      and electronics as the first indication of the possible presence of BFRs. To
      investigate the possible BFRs present, a total of 21 dust samples were collected
      from surfaces of electronic equipment and office furniture and were analysed
      using gas chromatography-mass spectrometry (GC-MS). The concentrations of ?7 BDE-
      congeners ranged from 50 to 3346ngng-1. Of the ?7 BDE congeners analysed, BDE
      209, -183 and -99 were the most dominant congeners. The concentrations observed
      ranged from <LOD - 1758, <LOD - 401 and <LOD-543ngg-1, for BDE-209, -183 and -99,
      respectively. T-HBCDD and 2-ethyl-1-hexyl-2.3.4.5-tetrabromobenzoate (EH-TBB)
      were detected in 57 and 67% of the total dust samples analysed with
      concentrations ranging from <LOD - 673 and <LOD - 385ngg-1, respectively.
      However, Bis (2-ethylhexyl) tetrabromophthalate (BEH-TEBP) was only detected in
      24% of the 21 samples exhibiting a concentration range of <LOD - 63ngg-1. The
      detection frequency of 1,2 Bis (2.4.6-tribromophenoxy) ethane (BTBPE) was 81%
      with concentrations of <LOD-1402ngg-1. Alongside the legacy BFRs, NBFRs were the
      most detected indicating probably increased usage as replacements for the banned
      commercial PBDEs products namely, penta-, octa-, and deca-BDE mixtures. No
      correlation was observed between the bromine levels obtained using portable XRF
      and the BFRs detected using GC-MS (r=0.0073, p=0.076). The observed trend may be
      attributed to various factors including the sample matrix analysed and the number
      of BFRs analysed. The observed trend is consistent with those reported from other
      studies.

PMID- 29216469
TI  - Background element content of the lichen Pseudevernia furfuracea: A supra
      national state of art implemented by novel field data from Italy.
AB  - In biomonitoring, the knowledge of background element content (BEC) values is an
      essential pre-requisite for the correct assessment of pollution levels. Here, we
      estimated the BEC values of a highly performing biomonitor, the epiphytic lichen
      Pseudevernia furfuracea, by means of a careful review of literature data,
      integrated by an extensive field survey. Methodologically homogeneous element
      content datasets, reflecting different exposure conditions across European and
      extra-European countries, were compiled and comparatively analysed. Element
      content in samples collected in remote areas was compared to that of potentially
      enriched samples, testing differences between medians for 25 elements. This
      analysis confirmed that the former samples were substantially unaffected by
      anthropogenic contributions, and their metrics were therefore proposed as a first
      overview at supra-national background level. We also showed that bioaccumulation
      studies suffer a huge methodological variability. Limited to original field data,
      we investigated the background variability of 43 elements in 62 remote Italian
      sites, characterized in GIS environment for anthropization, land use, climate and
      lithology at different scale resolution. The relationships between selected
      environmental descriptors and BEC were tested using Principal Component
      Regression (PCR) modelling. Elemental composition resulted significantly
      dependent on land use, climate and lithology. In the case of lithogenic elements,
      regression models correctly reproduced the lichen content throughout the country
      at randomly selected sites. Further descriptors should be identified only for As,
      Co, and V. Through a multivariate approach we also identified three
      geographically homogeneous macro-regions for which specific BECs were provided
      for use as reference in biomonitoring applications.

PMID- 29216470
TI  - Occurrence and risk assessment of antibiotics in water and lettuce in Ghana.
AB  - Hospital wastewater and effluents from waste stabilization ponds in Kumasi,
      Ghana, are directly discharged as low quality water into nearby streams which are
      eventually used to irrigate vegetables. The presence of 12 commonly used
      antibiotics in Ghana (metronidazole, ciprofloxacin, erythromycin, trimethoprim,
      ampicillin, cefuroxime, sulfamethoxazole, amoxicillin, tetracycline,
      oxytetracycline, chlortetracycline and doxycycline) were investigated in water
      and lettuce samples collected in three different areas in Kumasi, Ghana. The
      water samples were from hospital wastewater, wastewater stabilization ponds,
      rivers and irrigation water, while the lettuce samples were from vegetable farms
      and market vendors. Antibiotics in water samples were extracted using SPE while
      antibiotics in lettuce samples were extracted using accelerated solvent
      extraction followed by SPE. All extracted antibiotics samples were analyzed by
      HPLC-MS/MS. All studied compounds were detected in concentrations significantly
      higher (p=0.01) in hospital wastewater than in the other water sources. The
      highest concentration found in the present study was 15MUg/L for ciprofloxacin in
      hospital wastewater. Irrigation water samples analyzed had concentrations of
      antibiotics up to 0.2MUg/L. Wastewater stabilization ponds are low technology but
      effective means of removing antibiotics with removal efficiency up to 95%
      recorded in this study. However, some chemicals are still found in levels
      indicating medium to high risk of antibiotics resistance development in the
      environment. The total concentrations of antibiotics detected in edible lettuce
      tissues from vegetable farms and vegetable sellers at the markets were in the
      range of 12.0-104 and 11.0-41.4ng/kg (fresh weight) respectively. The antibiotics
      found with high concentrations in all the samples were sulfamethoxazole,
      erythromycin, ciprofloxacin, cefuroxime and trimethoprim. Furthermore, our study
      confirms the presence of seven antibiotics in lettuce from irrigation farms and
      markets, suggesting an indirect exposure of humans to antibiotics through
      vegetable consumption and drinking water in Ghana. However, estimated daily
      intake for a standard 60kg woman was 0.3ng/day, indicating low risk for human
      health.

PMID- 29216471
TI  - Annual cycle of dimethylsulfoniopropionate (DMSP) and dimethylsulfoxide (DMSO)
      related to phytoplankton succession in the Southern North Sea.
AB  - The influence of abiotic and biotic variables on the concentration of dimethyl
      sulfide (DMS), dimethylsulfoniopropionate (DMSP), and dimethylsulfoxide (DMSO),
      were investigated during an annual cycle in 2016 in the Belgian Coastal Zone
      (BCZ, North Sea). We reported strong seasonal variations in the concentration of
      these compounds linked to the phytoplankton succession with high DMS(P,O)
      producers (mainly Phaeocystis globosa) occurring in spring and low DMS(P,O)
      producers (various diatoms species) occurring in early spring and autumn. Spatial
      gradients of DMS and DMSP were related to those of phytoplankton biomass itself
      related to the inputs of nutrients from the Scheldt estuary. However, the use of
      a relationship with Chlorophyll-a (Chl-a) concentration is not sufficient to
      predict DMSP. Accounting for the phytoplankton composition, two different DMSP
      versus Chl-a correlations could be established, one for diatoms and another one
      for Phaeocystis colonies. We also reported high nearshore DMSO concentrations
      uncoupled to Chl-a and DMSP concentrations but linked to high suspended
      particulate matter (SPM) presumably coming from the Scheldt estuary as indicated
      by the positive relationship between annual average SPM and salinity.

PMID- 29216472
TI  - Unravelling metal mobility under complex contaminant signatures.
AB  - Metals are concerning pollutants in estuaries, where contamination can undergo
      significant remobilisation driven by physico-chemical forcing. Environmental
      concentrations of metals in estuarine sediments are often higher than natural
      backgrounds, but show no contiguity to potential sources. Thus, better
      understanding the metal mobility in estuaries is essential to improve
      identification of pollution sources and their accountability for environmental
      effects. This study aims to identify the key biogeochemical drivers of metal
      mobilisation on contaminated estuarine sediments through (1) evaluation of the
      potential mobilisation under controlled conditions, and (2) investigation of the
      relevance of metal mobilisation for in situ pollution levels in an area with
      multiple contaminant sources. Sediments from a saltmarsh adjacent to a coastal
      landfill, a marina, and a shipyard on the Thames Estuary (Essex, UK) were exposed
      in the laboratory (24h, N=96, 20 degrees C) to water under various salinity, pH,
      and redox potential. Major cations, Fe(II), and trace metal concentrations were
      analysed in the leachate and sediment. Salinity, pH and redox had a significant
      effect on metal mobilisation (p<0.001), e.g. under certain conditions Fe(II)
      leaching was increased ~1000-fold. Measurements in situ of surface and subsurface
      sediment cores revealed that landfill proximity poorly explained metal spatial
      distribution. However, physicochemical parameters explained up to 97% of
      geochemically normalized metal concentrations in sediments. Organic matter and pH
      were dominant factors for most of the metal concentrations at the sediment
      surface. At subsurface, major cations (Ca, Na, Mg and K) were determinant
      predictors of metal concentrations. Applying the empirical model obtained in the
      laboratory to geochemical conditions of the studied saltmarsh it was possible to
      demonstrate that Fe mobilisation regulates the fate of this (and other) metal in
      that area. Thus, present results highlight the importance of metal mobility to
      control sediment pollution and estuarine fate of metals.

PMID- 29216474
TI  - Magnetic Resonance Neurography of Traumatic and Nontraumatic Peripheral
      Trigeminal Neuropathies.
AB  - PURPOSE: The clinical neurosensory testing (NST) is currently the reference
      standard for the diagnosis of traumatic and nontraumatic peripheral trigeminal
      neuropathies (PTNs), but exhibits both false-positive and false-negative results
      compared with surgical findings and frequently results in treatment decision
      delays. We tested the hypothesis that magnetic resonance neurography (MRN) of
      PTNs can serve as a diagnostic modality by correlating the NST, MRN, and surgical
      findings. MATERIALS AND METHODS: Sixty patients with traumatic and nontraumatic
      PTN of varying etiologies and Sunderland classifications underwent NST, followed
      by MRN using 1.5T and 3.0T scanners. The protocol included 2-dimensional and 3
      dimensional (3D) imaging, including diffusion imaging and isotropic 3D PSIF. The
      MRN findings were read by 2 readers in consensus with the clinical findings but
      without knowing the side of abnormality. The MRN results were summarized using
      the Sunderland classification. In 26 patients, surgery was performed, and the
      Sunderland classification was assigned using the surgical photographs. Agreement
      between the MRN findings and NST/surgical classification was evaluated using
      kappa statistics. Pearson's correlation coefficient was used to assess the
      correlation between continuous measurements of MRN/NST and surgical
      classification. RESULTS: Of the 60 patients, 19 males and 41 females, mean age 41
      years (range 12 to 75), with 54 complaints of altered sensation of the lip, chin,
      or tongue, including 16 with neuropathic pain and 4 with no neurosensory
      complaint, were included. Third molar surgery (n = 29) represented the most
      common cause of traumatic PTN. Assuming 1 nerve abnormality per patient, the
      lower class was accepted, a kappa of 0.57 was observed between the MRN and NST
      classification. A kappa of 0.5 was found between MRN and surgical findings with a
      Pearson correlation coefficient of 0.67. CONCLUSIONS: MRN anatomically maps PTNs
      and stratifies the nerve injury and neuropathies with moderate to good agreement
      with NST and surgical findings for clinical use.

PMID- 29216475
TI  - Long-Face Dentofacial Deformities: Occlusion and Facial Esthetic Surgical
      Outcomes.
AB  - PURPOSE: The purpose of this study was to document malocclusion and facial
      dysmorphology in a series of patients with long face (LF) and chronic obstructive
      nasal breathing before treatment and the outcomes after bimaxillary orthognathic,
      osseous genioplasty, and intranasal surgery. MATERIALS AND METHODS: A
      retrospective cohort study of patients with LF undergoing bimaxillary, chin, and
      intranasal (septoplasty and inferior turbinate reduction) surgery was
      implemented. Predictor variables were grouped into demographic, anatomic,
      operative, and longitudinal follow-up categories. Primary outcome variables were
      the initial postoperative occlusion achieved (T2; 5 weeks after surgery) and the
      occulsion maintained long-term (>2 years after surgery). Six key occlusion
      parameters were assessed: overjet, overbite, coincidence of dental midlines,
      canine Angle classification, and molar vertical and transverse positions. The
      second outcome variable was the facial esthetic results. Photographs in 6 views
      were analyzed to document 7 facial contour characteristics. RESULTS: Seventy
      eight patients met the inclusion criteria. Average age at surgery was 24 years
      (range, 13 to 54 yr). The study included 53 female patients (68%). Findings
      confirmed that occlusion after initial surgical healing (T2) met the objectives
      for all parameters in 97% of patients (76 of 78). Most (68 of 78; 87%) maintained
      a favorable anterior and posterior occlusion for each parameter studied long-term
      (mean, 5 years 5 months). Facial contour deformities at presentation included
      prominent nose (63%), flat cheekbones (96%), flat midface (96%), weak chin (91%),
      obtuse neck-to-chin angle (56%), wide lip separation (95%), and excess maxillary
      dental show (99%). Correction of all pretreatment facial contour deformities was
      confirmed in 92% of patients after surgery. Long face patients with higher
      preoperative body mass index levels were more likely to have residual facial
      dysmorphology after surgery (P = .0009). CONCLUSION: Using orthognathic surgery
      techniques, patients with LF dentofacial deformity achieved the planned occlusion
      and most maintained the corrected occlusion long-term. In unoperated patients
      with LF, a "facial esthetic type" was identified. Orthognathic surgery proved
      effective in correcting associated facial dysmorphology in most patients.

PMID- 29216473
TI  - The natural sesquiterpene lactones arglabin, grosheimin, agracin, parthenolide,
      and estafiatin inhibit T cell receptor (TCR) activation.
AB  - Inhibition of the T cell receptor (TCR) pathway represents an effective strategy
      for the treatment of T cell-mediated inflammatory and autoimmune diseases. To
      identify natural compounds that could inhibit inflammatory T cell responses, we
      screened 13 sesquiterpene lactones, including achillin, arglabin, argolide,
      argracin, 3beta-hydroxyarhalin, artesin, artemisinin, estafiatin, grosheimin,
      grossmisin, leucomisine, parthenolide, and taurine, for their ability to modulate
      activation-induced Ca2+ mobilization in Jurkat T cells. Five of the compounds
      (arglabin, grosheimin, argracin, parthenolide, and estafiatin) inhibited anti-CD3
      induced mobilization of intercellular Ca2+ ([Ca2+]i) in Jurkat cells, with the
      most potent being parthenolide and argacin (IC50 = 5.6 and 6.1 MUM,
      respectively). Likewise, phosphorylation of extracellular signal-regulated kinase
      (ERK) 1/2 in activated Jurkat cells was inhibited by these five compounds, with
      the most potent being parthenolide and estafiatin (IC50 = 13.8 and 15.4 MUM,
      respectively). These compounds also inhibited ERK1/2 phosphorylation in primary
      human T cells and depleted intracellular glutathione. In contrast, none of the
      sesquiterpene lactones inhibited ERK1/2 phosphorylation in HL60 cells transfected
      with N-formyl peptide receptor 2 (FPR2) and stimulated with the FPR2 peptide
      agonist WKYMVM, indicating specificity for T cell activation. Estafiatin, a
      representative sesquiterpene lactone, was also profiled in a cell-based
      phosphokinase array for 43 kinase phosphorylation sites, as well as in a cell
      free competition binding assay for its ability to compete with an active-site
      directed ligand for 95 different protein kinases. Besides inhibition of ERK1/2
      phosphorylation, estafiatin also inhibited phosphorylation of p53, AMPKalpha1,
      CREB, and p27 elicited by TCR activation in Jurkat cells, but it did not bind to
      any of 95 kinases evaluated. These results suggest that arglabin, grosheimin,
      agracin, parthenolide, and estafiatin can selectively inhibit initial phases of
      TCR activation and may be natural compounds with previously undescribed
      immunotherapeutic properties.

PMID- 29216476
TI  - Is There a Role for Oxidative Stress in Temporomandibular Joint Disorders?
AB  - PURPOSE: Data on the role of oxidative stress in temporomandibular joint (TMJ)
      disorders are limited. This study compared serum levels of oxidative stress
      indicators and antioxidant enzymes in patients with TMJ disorders. PATIENTS AND
      METHODS: In this prospective study, patients with TMJ disorders and healthy
      controls were compared for descriptive characteristics (age and gender) and serum
      levels of malondialdehyde (MDA), an oxidative stress marker, and antioxidant
      enzymes catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD).
      RESULTS: This study included 32 patients with TMJ disorders and 32 healthy
      controls. There were no differences between the 2 groups for age (P = .98) and
      gender (P = .599). MDA levels were higher in the TMJ disorders group than in the
      control group (P < .001), whereas serum levels of CAT, SOD, and GSH were
      significantly higher in the control group (P < .001 for all comparisons). There
      was no correlation between age or gender and MDA, SOD, CAT, and GSH levels in the
      TMJ disorders or control group. CONCLUSION: Oxidative stress markers might have
      promising potential as biomarkers in the diagnostic strategy and therapeutic
      targets of TMJ disorders.

PMID- 29216477
TI  - Human laterality for manipulation and gestural communication related to 60
      everyday activities: Impact of multiple individual-related factors.
AB  - Literature on laterality emphasises the importance of implementing a
      comprehensive investigation of humans' and non-humans' laterality for both non
      communication and communication functions. Adopting a global approach should
      enhance our understanding of the mechanistic drivers of human brain functional
      lateralisation and help to explore further the nature of the left-hemispheric
      systems for both functions. This study investigated human laterality for both
      functions by taking, for the first time, numerous behaviours and multiple
      potential influential factors into consideration. We analysed replies to the
      Rennes Laterality Questionnaire that takes into account simultaneously:
      participants' behavioural, demographic and social characteristics as well as
      their genetic/social learning components and collateral factors such as health
      problems. We collected and analysed a large data set including 450,220 item
      responses (317,594 items related to behavioural laterality and 132,626 items
      related to personal information) by 5904 participants. The majority of
      participants were right-lateralised for nine behavioural categories. The
      laterality of right-lateralised individuals for the behaviours considered varied
      very little between behavioural categories, contrary to the laterality of
      ambiguously- and left-lateralised individuals. This is the first evidence of the
      stability of right-lateralised individuals and the relative flexibility of
      ambiguously- and left-lateralised individuals with regards to behavioural
      laterality related to 60 everyday activities. Moreover, the laterality patterns
      of our study population were linked in particular to the following individual
      related factors: demographic characteristics (current continent of residence),
      social characteristics (socio-professional group and study level), and collateral
      factors (writing hand, forced right-hand use, guiding eye, and health problems
      related to ear and back). We discuss our findings in relation to the evolutionary
      roots of human brain lateralisation for non-communication and communication
      functions.

PMID- 29216478
TI  - Reach and grasp deficits following damage to the dorsal pulvinar.
AB  - Expansion of the dorsal pulvinar in humans and its anatomical connectivity
      suggests its involvement in higher-order cognitive and visuomotor functions. We
      investigated visuomotor performance in a 31 year old patient (M.B.) with a lesion
      centered on the medial portion of the dorsal pulvinar (left > right) due to an
      atypical Sarcoidosis manifestation. Unlike lesions with a vascular etiology, the
      lesion of M.B. did not include primary sensory or motor thalamic nuclei. Thus,
      this patient gave us the exceedingly rare opportunity to study the contribution
      of the dorsal pulvinar to visuomotor behavior in a human without confounding
      losses in primary sensory or motor domains. We investigated reaching, saccade and
      visual decision making performance. Patient data in each task was compared to at
      least seven age matched healthy controls. While saccades were hypometric towards
      both hemifields, the patient did not show any spatial choice bias or perceptual
      deficits. At the same time, he exhibited reach and grasp difficulties, which
      shared features with both, parietal and cerebellar damage. In particular, he had
      problems to form a precision grip and exhibited reach deficits expressed in
      decreased accuracy, delayed initiation and prolonged movement durations. Reach
      deficits were similar in foveal and extrafoveal viewing conditions and in both
      visual hemifields but were stronger with the right hand. These results suggest
      that dorsal pulvinar function in humans goes beyond its subscribed role in visual
      cognition and is critical for the programming of voluntary actions with the
      hands.

PMID- 29216479
TI  - Diagnosis of deep vein thrombosis recurrence: Ultrasound criteria.
AB  - INTRODUCTION: Recurrent deep vein thrombosis (DVT) is often suspected in patients
      after anticoagulant drug withdrawal. The clinical signs can be confused with the
      onset of post-thrombotic syndrome. For these reasons, diagnosis of DVT recurrence
      must rely on an accurate method. MATERIALS AND METHODS: In order to assess this
      challenging clinical issue, we performed an overview of the literature regarding
      ultrasound criteria for the diagnosis of recurrent DVT through a Medline search,
      which included articles published from January 1, 1980 to February 20, 2017.
      RESULTS: Eighty-eight publications were found based on the defined keywords, of
      which nine articles with a relevant abstract were selected. By searching the
      reference lists of these nine articles, we obtained another 27 relevant articles.
      A new non-compressible vein or an increase in the diameter of a previously
      thrombosed vein segment by >4mm are sufficient to confirm the diagnosis of DVT
      recurrence. In contrast, an increase in diameter of <2mm enables recurrence to be
      ruled out. An increase between 2 and 4mm is deemed equivocal. Criteria based on
      echogenicity and Doppler venous blood flow are not reproducible. Other diagnostic
      imaging methods, mainly direct thrombus magnetic resonance imaging, are currently
      under evaluation. CONCLUSIONS: Ultrasound remains the most useful test for the
      diagnosis of recurrent DVT. Further imaging tests need to be validated.

PMID- 29216480
TI  - Comparison of pharmaceutical abatement in various water matrices by conventional
      ozonation, peroxone (O3/H2O2), and an electro-peroxone process.
AB  - Pharmaceutical abatement in a groundwater (GW), surface water (SW), and secondary
      effluent (SE) by conventional ozonation, the conventional peroxone (O3/H2O2), and
      the electro-peroxone (E-peroxone) processes was compared in batch tests. SE had
      significantly more fast-reacting dissolved organic matter (DOM) moieties than GW
      and SW. Therefore, O3 decomposed much faster in SE than in GW and SW. At specific
      ozone doses of 0.5-1.5 mg O3/mg dissolved organic carbon (DOC), the application
      of O3/H2O2 and E-peroxone process (by adding external H2O2 stocks or in-situ
      generating H2O2 from cathodic O2 reduction during ozonation) similarly enhanced
      the OH yield from O3 decomposition by ~5-12% and 5-7% in GW and SW, respectively,
      compared to conventional ozonation. In contrast, due to the slower reaction
      kinetics of O3 with H2O2 than O3 with fast-reacting DOM moieties, the addition or
      electro-generation of H2O2 hardly increased the OH yield (<4% increases) in SE.
      Corresponding to the changes in the OH yields, the abatement efficiencies of
      ozone-resistant pharmaceuticals (ibuprofen and clofibric acid) increased
      evidently in GW (up to ~14-18% at a specific ozone dose of 1.5 mg O3/mg DOC),
      moderately in SW (up to 6-10% at 0.5 mg O3/mg DOC), and negligibly in SE during
      the O3/H2O2 and E-peroxone treatment compared to conventional ozonation. These
      results indicate that similar to the conventional O3/H2O2 process, the E-peroxone
      process can more pronouncedly enhance O3 transformation to OH, and thus increase
      the abatement efficiency of ozone-resistant pharmaceuticals in water matrices
      exerting relatively high ozone stability (e.g., groundwater and surface water
      with low DOM contents). Therefore, by installing electrodes in existing ozone
      reactors, the E-peroxone process may provide a convenient way to enhance
      pharmaceutical abatement in drinking water applications, where groundwater and
      surface water with low DOM contents are used as the source waters.

PMID- 29216481
TI  - Robust performance of a membrane bioreactor for removing antibiotic resistance
      genes exposed to antibiotics: Role of membrane foulants.
AB  - Antibiotic resistance genes (ARGs) are an emerging concern in wastewater
      treatment plants (WWTPs), as dissemination of ARGs can pose a serious risk to
      human health. Few studies, however, have quantified ARGs in membrane bioreactors
      (MBRs), although MBRs have been widely used for both municipal and industrial
      wastewater treatment. To reveal the capacity of MBRs for removal of ARGs and the
      response of membrane fouling after antibiotic exposure, five typical ARG subtypes
      (sulI, sulII, tetC, tetX and ereA) and int1 were quantified affiliated by
      systematic membrane foulants analysis in a laboratory-scale anoxic/aerobic
      membrane bioreactor (A/O-MBR). Sulfamethoxazole and tetracycline hydrochloride
      additions increased ARG abundances by 0.5-1.4 orders of magnitude in the
      activated sludge, while the ARG removal performance of the membrane module
      remained stable (or even increased with ARG absolute abundance in several cases),
      with the abundance of removed ARGs ranging from 0.6 to 5.6 orders of magnitude.
      Specifically, the distribution of ARGs in membrane foulants accounted for 13%-25%
      of the total absolute abundance of all tested MBR samples. Indeed, substantial
      fouling occurred after the antibiotic additions, with the mean concentrations of
      soluble microbial product (SMP) and extracellular polymeric substance (EPS)
      increasing by 340% and 220%, respectively, in a membrane fouling cycle; moreover,
      the contents of EPS and SMP in the membrane foulants were significantly
      correlated with the ARG absolute abundance of membrane foulants (p < 0.05), among
      which more significant correlations occurred between both the protein and
      polysaccharide of foulants than that with humic acid. The dense membrane fouling
      layer and the membrane itself constituted dual barriers that effectively avoided
      the leakage of ARGs from the membrane module. Our findings provide fundamental
      insights into the proliferation and removal of ARGs in MBR systems, and highlight
      the contribution of membrane fouling to ARG removals in terms of the potential of
      MBR as an effective strategy to reduce ARG levels in WWTP effluent.

PMID- 29216483
TI  - Additional prognostic value of brachial-ankle pulse wave velocity to coronary
      computed tomography angiography in patients with suspected coronary artery
      disease.
AB  - BACKGROUND AND AIMS: Increased arterial stiffness is associated with a higher
      risk of future cardiovascular events. We aimed to investigate whether information
      about arterial stiffness provides additional prognostic value to coronary
      computed tomography angiography (CCTA) findings. METHODS: A total of 523
      consecutive patients (mean age, 58.0 +/- 10.3 years; male, 60.6%) with suspected
      coronary artery disease (CAD), who underwent CCTA and brachial-ankle pulse wave
      velocity (baPWV) measurement within a month, were retrospectively analyzed. A
      composite of cardiovascular death, nonfatal myocardial infarction (MI), coronary
      revascularization, nonfatal stroke, and hospitalization for cardiovascular causes
      was assessed. RESULTS: During a median 43.9 months of follow-up (interquartile
      range, 11.6-66.9 months), the composite endpoint occurred in 66 patients (3
      cardiovascular deaths, 1 nonfatal MI, 35 coronary revascularizations, 16 nonfatal
      strokes, and 45 hospitalizations for cardiovascular causes). After adjustment for
      clinical risk factors and CCTA findings, higher baPWV was an independent
      prognostic factor for the composite endpoint (adjusted hazard ratio, 4.717; 95%
      confidence interval, 2.675-8.319; p < 0.001). The addition of baPWV to clinical
      risk factors and CCTA findings significantly improved the prediction of
      cardiovascular events (global chi2 score, from 132 to 154; p = 0.005).
      CONCLUSIONS: Arterial stiffness provides additional prognostic information to
      CCTA findings in patients with suspected CAD. The baPWV can serve as a useful
      clinical tool for risk stratification in this population.

PMID- 29216482
TI  - Enantiomeric profiling of chiral illicit drugs in a pan-European study.
AB  - The aim of this paper is to present the first study on spatial and temporal
      variation in the enantiomeric profile of chiral drugs in eight European cities.
      Wastewater-based epidemiology (WBE) and enantioselective analysis were combined
      to evaluate trends in illicit drug use in the context of their consumption vs
      direct disposal as well as their synthetic production routes. Spatial variations
      in amphetamine loads were observed with higher use in Northern European cities.
      Enantioselective analysis showed a general enrichment of amphetamine with the R-(
      )-enantiomer in wastewater indicating its abuse. High loads of racemic
      methamphetamine were detected in Oslo (EF = 0.49 +/- 0.02). This is in contrast
      to other European cities where S-(+)-methamphetamine was the predominant
      enantiomer. This indicates different methods of methamphetamine synthesis and/or
      trafficking routes in Oslo, compared with the other cities tested. An enrichment
      of MDMA with the R-(-)-enantiomer was observed in European wastewaters indicating
      MDMA consumption rather than disposal of unused drug. MDA's chiral signature
      indicated its enrichment with the S-(+)-enantiomer, which confirms its origin
      from MDMA metabolism in humans. HMMA was also detected at quantifiable
      concentrations in wastewater and was found to be a suitable biomarker for MDMA
      consumption. Mephedrone was only detected in wastewater from the United Kingdom
      with population-normalised loads up to 47.7 mg 1000 people-1 day-1. The
      enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests
      stereoselective metabolism in humans, hence consumption, rather than direct
      disposal of the drug. The investigation of drug precursors, such as ephedrine,
      showed that their presence was reasonably ascribed to their medical use.

PMID- 29216484
TI  - Beliefs about the causes of and treatments for depression and bipolar disorder
      among South Koreans.
AB  - Public beliefs about psychiatric disorders are important for understanding help
      seeking behaviours. We investigated factors that affect South Koreans' beliefs
      about the causes and treatment of depression and bipolar disorder. We recruited
      654 participants aged 15-54 years using an online panel survey. Participants
      completed two questionnaires: 34 possible causes of and 33 possible treatments
      for depression and bipolar disorder. For both disorders, the questionnaires about
      causes revealed four factors: social-environmental, God/fate, heath/lifestyle,
      and biological; the questionnaires about treatments revealed five factors: self
      help/stress management, physical treatment/health management, seeking mental
      health services, religious help, and resting. Causes of depression were more
      recognized as social-environmental, religious, and health/lifestyle compared to
      bipolar disorder. Participants expressed more beliefs in self-help/stress
      management, physical treatment/health management, seeking mental health services,
      and resting for depression, compared to bipolar disorder. Participants' beliefs
      about the causes of the disorders and their demographic and psychiatric
      characteristics were closely associated with beliefs about treatment validity.
      Participants' beliefs about the causes of depression and bipolar disorder
      significantly affected their beliefs about treatment. Therefore, strategies to
      improve mental health literacy should provide the aetiology of specific mental
      disorders. Further research using a representative community sample is needed to
      generalize our findings.

PMID- 29216486
TI  - The effects of microplastic on freshwater Hydra attenuata feeding, morphology &
      reproduction.
AB  - Microplastic pollution has been a growing concern in the aquatic environment for
      several years. The abundance of microplastics in the environment has invariably
      led them to interact with a variety of different aquatic species. The small size
      of microplastics may make them bioavailable to a great range of species however,
      the impact this may have is not fully understood. Much of the research on
      microplastic pollution has focused on the marine environment and species with
      little research undertaken in freshwater. Here we examine the effect of
      microplastics on the freshwater cnidarian, Hydra attenuata. This study also
      describes the development and use of a bioassay to investigate the impact of
      microplastic on freshwater organisms. Hydra attenuata play a vital role in the
      planktonic make up of slow moving freshwater bodies which they inhabit and are
      sensitive environmental indicators. Hydra attenuata were exposed to polyethylene
      flakes (<400 im) extracted from facewash at different concentrations (Control,
      0.01, 0.02, 0.04, 0.08 g mL-1). The ecologically relevant endpoint of feeding was
      measured by determining the amount of prey consumed (Artemia salina) after 30 and
      60 min. The amount of microplastics ingested was also recorded at 30 min and 60
      min. After which Hydra attenuata were transferred to clean media and observed
      after 3, 24, 48 & 96 h with changes in their morphology and reproduction
      (Hydranth numbers) recorded. The results of this study show that Hydra attenuata
      are capable of ingesting microplastics, with several individuals completely
      filling their gastric cavities. Significant reductions in feeding rates were
      observed after 30 min in 0.02 & 0.08 g mL-1 and after 60 min in 0.04 & 0.08 g mL
      1 exposures. Exposure to the microplastics caused significant changes to the
      morphology of Hydra attenuata, however these changes were non-lethal. This study
      demonstrates that freshwater Hydra attenuata is capable of ingesting
      microplastics and that microplastic can significantly impact the feeding of
      freshwater organisms.

PMID- 29216485
TI  - The association between rehabilitation programs and metabolic syndrome in chronic
      inpatients with schizophrenia.
AB  - The correlation between different rehabilitation programs and the prevalence of
      metabolic syndrome in people with schizophrenia is unclear. We tested the
      association in chronic inpatients with schizophrenia of a psychiatric hospital in
      Taiwan. Patients with schizophrenia and age from 20 to 65 years old were
      included. The criteria of metabolic syndrome were according to the adapted Adult
      Treatment Protocol for Asians. According to different types of rehabilitations,
      patients were divided into work group, occupational therapy group and daily
      activities group. A total of 359 chronic inpatients with schizophrenia were
      recruited. Participants had a mean age of 45.9 years and the prevalence of
      metabolic syndrome was 37.3%. There was a significantly higher prevalence of
      metabolic syndrome in the work group than in the daily activity group (adjusted
      odds ratio (aOR) = 1.91, 95% CI = 1.019-3.564, p < 0.05) after adjusted related
      confounders. Other factors associated with higher prevalence of metabolic
      syndrome included old age, female gender, low psychotic symptoms severity and
      clozapine user. This study identified a high prevalence of metabolic syndrome in
      chronic inpatients with schizophrenia especially in patients with good
      occupational function. Further investigation of the relationship between the
      occupational function and metabolic syndrome is necessary for chronic inpatients
      with schizophrenia.

PMID- 29216487
TI  - Microplastics increase impact of treated wastewater on freshwater microbial
      community.
AB  - Plastic pollution is a major global concern with several million microplastic
      particles entering every day freshwater ecosystems via wastewater discharge.
      Microplastic particles stimulate biofilm formation (plastisphere) throughout the
      water column and have the potential to affect microbial community structure if
      they accumulate in pelagic waters, especially enhancing the proliferation of
      biohazardous bacteria. To test this scenario, we simulated the inflow of treated
      wastewater into a temperate lake using a continuous culture system with a
      gradient of concentration of microplastic particles. We followed the effect of
      microplastics on the microbial community structure and on the occurrence of
      integrase 1 (int1), a marker associated with mobile genetic elements known as a
      proxy for anthropogenic effects on the spread of antimicrobial resistance genes.
      The abundance of int1 increased in the plastisphere with increasing microplastic
      particle concentration, but not in the water surrounding the microplastic
      particles. Likewise, the microbial community on microplastic was more similar to
      the original wastewater community with increasing microplastic concentrations.
      Our results show that microplastic particles indeed promote persistence of
      typical indicators of microbial anthropogenic pollution in natural waters, and
      substantiate that their removal from treated wastewater should be prioritised.

PMID- 29216488
TI  - Microbial community composition and PAHs removal potential of indigenous bacteria
      in oil contaminated sediment of Taean coast, Korea.
AB  - The tidal flats near Sinduri beach in Taean, Korea, have been severely
      contaminated by heavy crude oils due to the Korea's worst oil spill accident, say
      the Hebei Spirit Oil Spill, in 2007. Crude oil compounds, including polycyclic
      aromatic hydrocarbons (PAHs), pose significant environmental damages due to their
      wide distribution, persistence, high toxicity, mutagenicity, and carcinogenicity.
      Microbial community of Sinduri beach sediments samples was analyzed by
      metagenomic data with 16S rRNA gene amplicons. Three phyla (Proteobacteria,
      Firmicutes, and Bacteroidetes) accounted for approximately >=93.0% of the total
      phyla based on metagenomic analysis. Proteobacteria was the dominant phylum in
      Sinduri beach sediments. Cultivable bacteria were isolated from PAH-enriched
      cultures, and bacterial diversity was investigated through performing culture
      characterization followed by molecular biology methods. Sixty-seven isolates were
      obtained, comprising representatives of Actinobacteria, Firmicutes, alpha- and
      gamma-Proteobacteria, and Bacteroidetes. PAH catabolism genes, such as
      naphthalene dioxygenase (NDO) and aromatic ring hydroxylating dioxygenase
      (ARHDO), were used as genetic markers to assess biodegradation of PAHs in the
      cultivable bacteria. The ability to degrade PAHs was demonstrated by monitoring
      the removal of PAHs using a gas chromatography mass spectrometer. Overall,
      various PAH-degrading bacteria were widely present in Sinduri beach sediments and
      generally reflected the restored microbial community. Among them, Cobetia marina,
      Rhodococcus soli, and Pseudoalteromonas agarivorans were found to be significant
      in degradation of PAHs. This large collection of PAH-degrading strains represents
      a valuable resource for studies investigating mechanisms of PAH degradation and
      bioremediation in oil contaminated coastal environment, elsewhere.

PMID- 29216489
TI  - Alginate affects agglomeration state and uptake of 14C-labeled few-layer graphene
      by freshwater snails: Implications for the environmental fate of graphene in
      aquatic systems.
AB  - Understanding of the interaction of graphene with natural polysaccharides (e.g.,
      alginate) is crucial to elucidate its environmental fate. We investigated the
      impact of alginate on the agglomeration and stability of 14C-labeled few-layer
      graphene (FLG) in varying concentrations of monovalent (NaCl) and divalent
      (CaCl2) electrolytes. Enhanced agglomeration occurred at high CaCl2
      concentrations (>=5 mM) due to the alginate gel networks formation in the
      presence of Ca2+. FLG enmeshed within extended alginate gel networks was observed
      under transmission electron microscope and atomic force microscope. However,
      background Na+ competition for binding sites with Ca2+ at the alginate surfaces
      shielded the gelation of alginate. FLG was readily dispersed by alginate under
      environmentally relevant ionic strength conditions (i.e., <200 mM Na+ and <5 mM
      Ca2+). In comparison with the bare FLG, the slow sedimentation of the alginate
      stabilized FLG (158 MUg/L) caused continuous exposure of this nanomaterial to
      freshwater snails, which ingested 1.9 times more FLG through filter-feeding
      within 72 h. Moreover, surface modification of FLG by alginate significantly
      increased the whole-body and intestinal levels of FLG, but reduced the
      internalization of FLG to the intestinal epithelial cells. These findings
      indicate that alginate will act as a stabilizing agent controlling the transport
      of FLG in aqueous systems. This study also provides the first evidence that
      interaction of graphene with natural polysaccharides affected the uptake of FLG
      in the snails, which may alter the fate of FLG in aquatic environments.

PMID- 29216490
TI  - Phthalate esters on urban airborne particles: Levels in PM10 and PM2.5 from
      Mexico City and theoretical assessment of lung exposure.
AB  - Endocrine disrupting chemicals (EDCs) from the environment are associated with
      reproductive abnormalities (i.e. decreased sperm concentration; increased
      endometriosis) and alterations of the cardiovascular system (i.e. increased blood
      pressure and risk of coronary disease). Some phthalates esters have been
      identified as EDCs, for which inhalation is considered as one of the routes of
      exposure. However, only little is known regarding inhalational exposure to EDCs
      via urban airborne particles. In the present study, we report the monthly
      concentration of 8 phthalate esters measured in PM10 and PM2.5 collected and
      recovered during 7 months in a highly populated area of Mexico City. Using the
      levels of PM10 and PM2.5 reported by the automatized network of environmental
      monitoring of Mexico City for the sampling site, we estimated exposure levels for
      people of different ages and gender. Two endocrine disrupting compounds, the
      phthalate esters DEHP and DnBP, were found on the particles in higher
      concentrations during the warmer months of the year. The highest concentration
      was reported for DEHP (229.7MUg/g of particles) in PM2.5 collected in May 2013.
      After calculations of the DEHP concentration in the atmosphere, and using the
      respiratory flow rate, we determined males were potentially exposed to larger
      quantities of DEHP, reaching up to 18ng/8h in April 2013. Despite the
      concentrations of phthalates seem to be rather small, a comprehensive
      characterization of its presence is necessary in order to evaluate the overall
      exposure to these compounds, providing a clear view of exposure on children,
      adolescents and pregnant women.

PMID- 29216491
TI  - Microbial source tracking markers associated with domestic rainwater harvesting
      systems: Correlation to indicator organisms.
AB  - Domestic rainwater harvesting (tank water) systems were screened for the presence
      of a panel of microbial source tracking (MST) markers and traditional indicator
      organisms. The indicator organisms were enumerated utilizing traditional culture
      based methods, while the MST markers were quantified by quantitative PCR (qPCR).
      The indicators Escherichia coli (E. coli) and enterococci were also quantified
      using qPCR. Correlations and concurrence between these parameters were then
      investigated to determine which markers could be utilized to supplement
      traditional indicator analysis. Quantitative PCR analysis indicated that
      Bacteroides HF183, adenovirus, Lachnospiraceae and E. coli were detected and
      quantifiable in 100% of the tank water samples collected throughout the sampling
      period, while human mitochondrial DNA (mtDNA) was quantifiable in 90% of the tank
      water samples and Bifidobacterium adolescentis (B. adolescentis) and enterococci
      were quantifiable in 67% of the tank water samples, respectively. Significant
      positive correlations were recorded for Lachnospiraceae versus heterotrophic
      bacteria (p = 0.000), adenovirus versus E. coli (culturing) (p = 0.000) and
      heterotrophic bacteria (p = 0.024), the HF183 marker versus E. coli (qPCR) (p =
      0.024) and B. adolescentis versus fecal coliforms (p = 0.037). In addition, 100%
      concurrence was observed for the HF183 marker, adenovirus and Lachnospiraceae
      versus E. coli (qPCR), enterococci (qPCR) and heterotrophic bacteria, amongst
      others. Based on the correlations and the concurrence analysis, the HF183 marker,
      Lachnospiraceae and adenovirus may be utilized to supplement indicator organism
      analysis for the monitoring of harvested rainwater quality.

PMID- 29216492
TI  - Production of new activated bio-carbons by chemical activation of residue left
      after supercritical extraction of hops.
AB  - A technology of activated bio-carbons production from the residue left after
      supercritical extraction of hops is described. The effect of the variant of
      chemical activation and impregnation ratio on the physicochemical properties as
      well as sorption capacity towards toxic gas of acidic character (nitrogen
      dioxide), basic organic dye (aqueous solution of methylene blue - MB) and iodine
      was investigated. The materials obtained were activated bio-carbons of well
      developed surface area ranging between 897 and 1095m2/g, showing clearly acidic
      character of the surface. The sorption tests results proved that chemical
      activation of the residue left after supercritical extraction of hops allows
      obtaining activated bio-carbons with very high sorption capacity towards nitrogen
      dioxide, reaching to 77.2 and 155.3mg/g in dry and wet conditions, respectively.
      The maximum sorption capacity of the adsorbents towards methylene blue was
      328.75mg/g, while towards iodine 1815mg/g. The equilibrium data for aqueous
      solution of MB were analyzed by the Langmuir and Freundlich models, whereas the
      kinetics of the adsorption process was studied using pseudo-first and second
      order models. According to the obtained data, the adsorption of MB from aqueous
      solution is better described by Langmuir model and pseudo-second order kinetic
      model.

PMID- 29216493
TI  - Intimate partner violence against women, circumstances of aggressions and oral
      maxillofacial traumas: A medical-legal and forensic approach.
AB  - INTRODUCTION: Intimate partner violence (IPV) is a serious public health problem
      that frequently results in oral-maxillofacial traumas, generating high social and
      economic costs. The aim of this study was to describe the profile of women
      victims of IPV and determine the pattern of oral-maxillofacial traumas, according
      to a medical-legal and forensic perspective. An exploratory study of 1361
      suspected cases of women victims of IPV was carried out based on database of an
      Institute of Legal Medicine and Forensic Dentistry of Northeastern Brazil during
      a period of 4 years. Medico-legal and social records of victims were searched for
      information related to sociodemographic data, circumstances of aggressions and
      trauma patterns. Descriptive and multivariate statistics and Multiple
      Correspondence Analysis (MCA) were performed. MAIN RESULTS: Almost half of
      victims exhibited some oral-maxillofacial trauma resulting from IPV (45.8%).
      Lesions affecting more than one third of the face (41.3%), especially in soft
      tissues (96.1%) were the most common. Based on the MCA results, two distinct
      victimization profiles (P1 and P2) have been identified. P1 was mainly
      characterized by women aged less than 28 years, living in the urban area, with
      higher education and working. They were assaulted using physical force in
      community settings perpetrated by former partner or ex-boyfriend during the night
      and weekends, resulting in oral-maxillofacial traumas. P2 was mainly composed of
      women aged over 28 years, living in the suburban or rural areas, with low
      schooling and who did not work. They were assaulted by firearm or weapon in their
      own home, perpetrated by their partner or boyfriend during the day and weekdays,
      resulting in trauma to other body parts. CONCLUSIONS: Oral and maxillofacial
      traumas are very common among women victims of IPV who searched for medical-legal
      service. In this context, forensic dentists can play a key role during the
      diagnostic process and should always work together with medical, biochemical and
      toxicological experts. The findings of this study may contribute to the
      formulation of evidence-based policies.

PMID- 29216494
TI  - Mutagenesis of the FAE1 genes significantly changes fatty acid composition in
      seeds of Camelina sativa.
AB  - Camelina sativa is a re-emerging low-input oilseed crop that has great
      potentials. It is necessary to ameliorate camelina oils for optimized fatty acid
      composition that can meet different application requirements. Camelina seed
      contains significant amounts of C20-C24 very long-chain fatty acids (VLCFAs) that
      may not be desirable. We demonstrated that these VLCFAs can be effectively
      reduced by deactivating the Fatty Acid Elongase1 (FAE1) in camelina. The
      allohexaploid camelina contains three alleles of FAE1 genes. Ethyl
      methanesulfonate (EMS) induced mutation at the FAE1-B gene caused over 60%
      reduction of VLCFAs in seed. Homozygous knockout mutants were successfully
      created in a single generation by simultaneously targeting three FAE1 alleles
      using the CRISPR technology with an egg cell-specific Cas9 expression. VLCFAs
      were reduced to less than 2% of total fatty acids compared to over 22% in the
      wild type, and the C18 unsaturated fatty acids were concomitantly increased. The
      fae1 mutants were indistinguishable from wild type in seed physiology and plant
      growth. This study demonstrated that the CRISPR/Cas9 technology can be
      effectively applied to the polyploid crop camelina to rapidly obtain desired
      traits such as optimal fatty acid composition in its seed oil. Knocking out FAE1
      also provides a means to increase the levels of oleic acid or alpha-linolenic
      acid in camelina oils that are desirable for industrial or food/feed uses.

PMID- 29216495
TI  - Equipping providers with principles, knowledge and skills to successfully
      integrate behaviour change counselling into practice: a primary healthcare
      framework.
AB  - OBJECTIVES: There is an urgent need for healthcare providers and healthcare
      systems to support productive interactions with patients that promote sustained
      health behaviour change in order to improve patient and population health
      outcomes. Behaviour change theories and interventions have been developed and
      evaluated in experimental contexts; however, most healthcare providers have
      little training, and therefore low confidence in, behaviour change counselling.
      Particularly important is how to integrate theory and method to support
      healthcare providers to engage in behaviour change counselling competently. In
      this article, we describe a general training model developed from theory,
      evidence, experience and stakeholder engagement. This model will set the stage
      for future evaluation research on training needed to achieve competency,
      sustainability of competency, as well as effectiveness/cost-effectiveness of
      training in supporting behaviour change. DESIGN AND METHODS: A framework to
      support competency based training in behaviour change counselling is described in
      this article. This framework is designed to be integrative, sustainable, scalable
      and capable of being evaluated in follow-up studies. RESULTS AND DISCUSSION:
      Effective training in behaviour change counselling is critical to meet the
      current and future healthcare needs of patients living with, or at risk of,
      chronic diseases. Increasing competency in establishing change-based
      relationships, assessing and promoting readiness to change, implementing
      behaviour modification and addressing psychosocial issues will be value added to
      the healthcare system.

PMID- 29216496
TI  - The impact of new national guidance for the public health management of enteric
      fever in England.
AB  - OBJECTIVES: New guidance was published in England in February 2012 to support the
      public health management of enteric fever and reduce the risks of secondary
      transmission. The new guidance was evaluated to assess: STUDY DESIGN:
      Quantitative and qualitative evaluation of the implementation of new public
      health guidance. METHODS: A qualitative review of all non-travel-related cases
      from February 2010 to January 2014 to compare the risk of secondary transmission
      before and after the guidance introduction; an audit of clearance sampling for
      each case and their contacts reported in London from February 2012-January 2015
      to compare with a previous London audit; and an online user survey in November
      2014. RESULTS: The proportions of non-travel cases reported before and after the
      introduction of the new guidance were similar, 6% in 2010-2012 compared to 7% in
      2012-2014 (P = 0.33). There was a 32% reduction in the number of clearance
      samples required for cases and the estimated period of exclusion from work or
      school was reduced from 54 days to 16 days. Compliance in case clearance improved
      from 53% to 90% and contact screening compliance improved from 42% to 80%. The
      targeted screening of contacts led to a significantly higher positive yield (3.6%
      from 1.5%, P = 0.003). All symptomatic co-travellers presented to a healthcare
      professional, suggesting that screening could be restricted to those in risk
      groups for transmission. Feedback from users highlighted additional areas, such
      as management of large organised groups of co-travellers and those diagnosed
      abroad, which has informed the update of the national guidance. CONCLUSIONS: The
      new guidance has not led to an increase in secondary transmission of enteric
      fever in England and findings have been used to inform an update of the guidance.
      The new guidance also represents a reduced burden of investigation and thus a
      likely reduced cost to patients, healthcare professionals, laboratories and
      environmental health officers.

PMID- 29216497
TI  - Engineering the bioconversion of methane and methanol to fuels and chemicals in
      native and synthetic methylotrophs.
AB  - Methylotrophy describes the ability of organisms to utilize reduced one-carbon
      compounds, notably methane and methanol, as growth and energy sources. Abundant
      natural gas supplies, composed primarily of methane, have prompted interest in
      using these compounds, which are more reduced than sugars, as substrates to
      improve product titers and yields of bioprocesses. Engineering native
      methylotophs or developing synthetic methylotrophs are emerging fields to convert
      methane and methanol into fuels and chemicals under aerobic and anaerobic
      conditions. This review discusses recent progress made toward engineering native
      methanotrophs for aerobic and anaerobic methane utilization and synthetic
      methylotrophs for methanol utilization. Finally, strategies to overcome the
      limitations involved with synthetic methanol utilization, notably methanol
      dehydrogenase kinetics and ribulose 5-phosphate regeneration, are discussed.

PMID- 29216498
TI  - Transcriptional responses to phosphate starvation in Brachypodium distachyon
      roots.
AB  - Brachypodium distachyon is a model plant that has recently emerged in grass
      research. Although the growth and photochemical efficiency of this species
      respond strongly to phosphate (Pi) availability, its Pi starvation response
      mechanism, which controls the Pi homeostasis, remains largely unknown. This study
      presents the transcriptomic response profiles of Pi-deficient roots at growth
      stages during which the plants were starved but obvious growth defects were
      absent. The results identify several phosphate transporters (i.e., PHO1), purple
      acid phosphatases, and SYG1/PHO81/XPR1 (SPX) domain-containing proteins out of a
      total of 1740 differentially expressed genes (DEGs). In particular, the
      transcription factor ethylene response factor (ERF), basic helix-loop-helix
      (bHLH), and WRKY family genes were the three most abundant DEG groups and the
      latter was significantly enriched. Comparative transcriptome analysis of
      Brachypodium versus Arabidopsis and rice revealed the presence of several common
      components in response to Pi fluctuations. Most significantly, jasmonic acid (JA)
      signaling-related genes were overrepresented in gene ontology (GO) enrichment
      tests. The presence of a possible link between low Pi response, inositol
      polyphosphates, and JA signaling is therefore discussed.

PMID- 29216499
TI  - Vitamin D3 decreases glycolysis and invasiveness, and increases cellular
      stiffness in breast cancer cells.
AB  - Breast cancer is one of the major causes of death in the USA. Cancer cells,
      including breast, have high glycolysis rates to meet their energy demands for
      survival and growth. Vitamin D3 (VD3) is important for many important
      physiological processes such as bone mineralization, but its anticancer role is
      yet to be proven. We find that VD3 treatment significantly down-regulates
      glycolytic enzymes and genes and decreases glucose uptake - for both lowly
      metastatic MCF-7 and highly metastatic MDA-MB-231 (MB231) breast cancer cells.
      VD3 also significantly decreases cell viability by inducing apoptosis -
      consistent with decreased expression of mammalian target of rapamycin (mTOR),
      which regulates glycolysis and cancer cell survival, and increases 5' adenosine
      monophosphate-activated protein kinase (AMPK) activation. These changes accompany
      a significant reduction of cell migration and increased cell stiffness,
      presumably a consequence of reversal of the epithelial to mesenchymal transition
      resulting in increased E-cadherin, and F-actin, and reduced vimentin expression.
      High levels of cytoskeletal and cortical F-actin may cause high cell stiffness.
      VD3-induced mechanical changes are stronger in highly metastatic MB231 than in
      lowly metastatic MCF-7 cells. Our results suggest therapeutic and preventive
      roles of VD3 in breast cancer.

PMID- 29216501
TI  - SMART coils for intracranial aneurysm embolization: Initial outcomes.
AB  - OBJECTIVES: Endovascular technology for the treatment of intracranial aneurysms
      continues to rapidly evolve. The SMART coil (Penumbra Inc., Alameda, CA, USA) is
      a novel microcoil designed to enhance deliverability. The aim of this single
      center, retrospective cohort study is to assess the initial outcomes after
      aneurysm embolization using SMART coils. PATIENTS AND METHODS: We reviewed
      consecutive patients with intracranial aneurysms who underwent endovascular
      embolization using SMART coils from June 2016 to January 2017. Baseline and
      initial outcomes data were analyzed. RESULTS: The study cohort was comprised of
      32 patients with 33 aneurysms. The mean age was 55.8 years. The majority (85%) of
      aneurysms were located in the anterior circulation. The mean aneurysm maximum
      diameter and neck width were 6.0mm and 3.1mm, respectively. Dome irregularity and
      fusiform aneurysm morphology were noted in 33% and 9% of aneurysms, respectively,
      and 15% presented with subarachnoid hemorrhage. No serious procedural
      complications occurred, including microcatheter prolapse, intraprocedural
      aneurysm rupture, or thromboembolism. Device malfunction occurred in one case
      (3%). The mean packing density was 25%, and the degree of immediate post
      embolization aneurysm occlusion was a modified Raymond-Roy grade I, II, IIIa, and
      IIIb in 48%, 27%, 18%, and 6%, respectively. CONCLUSION: Our preliminary findings
      suggest that the SMART coil has a favorable initial risk to benefit profile for
      the embolization of appropriately selected aneurysms. Additional studies of
      larger cohorts are necessary to determine the mid-term and long-term clinical and
      angiographic outcomes of aneurysm patients treated with the SMART coil.

PMID- 29216500
TI  - Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture
      defect healing.
AB  - The purpose of this work was to investigate new bone formation in macroporous
      iron foams coated with strontium (FeSr) or bisphosphonate (FeBiP) compared to
      plain iron foam (Fe) and empty defect in a critical size metaphyseal bone defect
      model in ovariectomized rats. 60 female rats were subjected to bilateral
      ovariectomy and multi-deficient diet for 3 months. A 4 mm wedge shaped
      metaphyseal osteotomy was created, fixed with a mini-plate and subsequently
      filled with Fe, FeSr, FeBiP or left empty. After 6 weeks, MUCt analysis revealed
      a statistically significant increased bone formation at the implant interface in
      FeSr compared to FeBiP (p = 0.035) and Fe (p = 0.002), respectively. Increased
      mineralized tissue was also seen within the pores in FeSr (p = 0.023) compared to
      Fe. Histomorphometry revealed significantly increased bone formation at the
      implant interface in FeSr (p < 0.001) and FeBiP (p = 0.006) compared to plain Fe
      with increased osteoblast and decreased osteoclast activity in combination with
      increased BMP2 and decreased RANKL/OPG in immunohistochemistry. ToF-SIMS analysis
      showed overlapping Ca signals with Fe for both FeSr and FeBiP thereby indicating
      tissue in-growth into the scaffolds. In conclusion, iron foam with strontium or
      bisphosphonate coating are of further interest in metaphyseal fracture defects in
      osteopenic bone.

PMID- 29216502
TI  - Intraventricular hemorrhage related to AVM rupture: Description, outcomes and
      impact of intraventricular fibrinolysis.
AB  - OBJECTIVES: Arteriovenous malformation (AVM) rupture could lead to
      intraventricular hemorrhage (IVH), a particularly severe form of intracranial
      bleeding. The epidemiology, presentation, management and outcomes of IVH related
      to AVM rupture have not been clearly addressed yet. The aim of the present study
      was to investigate the characteristics of IVH related to AVM rupture, with
      particular attention paid to functional outcomes and to the impact of
      intraventricular fibrinolysis (IVF). PATIENTS AND METHODS: Between 2011 and 2015,
      all patients suffering from IVH admitted in two tertiary neurosurgical centers
      were included in a prospective register. Patient with IVH related to AVM rupture
      were identified (n=29) and their data retrospectively collected. Particular
      attention was paid on patients who received IVF. We also compared them to 29
      apparied aneurysmal IVH. RESULTS: IVH related to AVM rupture often occurred in
      young patients. In most cases, intracerebral hemorrhage was associated to IVH.
      17% of the patients died, and functional outcome at 6 months was similar to those
      with aneurysmal IVH. Interestingly, 5 patients received IVF and none experienced
      any rebleeding. CONCLUSION: IVH related to AVM rupture is a severe form of
      hemorrhagic stroke, with a poor neurologic prognosis. IVF seems to be safe and
      may be considered in this particular form of IVH.

PMID- 29216503
TI  - Clinical and radiographic comparison of cervical disc arthroplasty with Prestige
      LP Disc and anterior cervical fusion: A minimum 6-year follow-up study.
AB  - OBJECTIVES: To retrospectively compare the long-term clinical and radiographic
      outcomes of cervical disc arthroplasty (CDA) with Prestige-LP Disc and anterior
      cervical discectomy and fusion (ACDF) for single-level cervical degenerative disc
      disease. PATIENTS AND METHODS: Ninety-eight patients (45 CDA and 53 ACDF) with a
      minimum 6-year follow-up were included. Clinical evaluations included Japanese
      Orthopedic Association (JOA), visual analogue scale (VAS), and Neck Disability
      Index (NDI) scores. Radiographic evaluations included sagittal alignment, range
      of motion (ROM) at the index and adjacent level, adjacent segment degeneration
      (ASD), and heterotopic ossification (HO). RESULTS: At the final follow-up, there
      were no significant differences in JOA, VAS neck, and VAS arm scores between the
      two groups. However, NDI scores improved more in the CDA group than in the ACDF
      group. The sagittal alignment was maintained in both groups. The ROM at the index
      level in the CDA group was decreased from 9.6+/-4.3 degrees  at baseline to 7.8+/
      4.7 degrees  at the final follow-up. The ROM at the cranial adjacent level in the
      ACDF group was increased. The incidence of ASD was lower in the CDA group than in
      the ACDF group (26.7% vs 49.1%, p=0.023). HO was observed in 46.7% of the
      patients but did not influence the clinical outcome. CONCLUSION: Both CDA with
      Prestige-LP Disc and ACDF showed good clinical outcomes at a minimum 6-year
      follow-up. Compared with ACDF, CDA preserved the motion and reduced the incidence
      of ASD.

PMID- 29216504
TI  - Burnout: Yes, it's a health problem, but is the solution partly linked to
      professionalism?

PMID- 29216505
TI  - Application of laryngeal mask ProtectorTM Cuff PilotTM for safe recovery from
      general anesthesia in a patient with difficult mask ventilation.

PMID- 29216506
TI  - T1, T2 paraverterbal blocks provide opioid sparing in first rib resection for
      thoracic outlet syndrome.

PMID- 29216507
TI  - Chimeric HCMV/HSV-1 and Deltagamma134.5 oncolytic herpes simplex virus elicit
      immune mediated antigliomal effect and antitumor memory.
AB  - Malignant gliomas are the most common primary brain tumor and are characterized
      by rapid and highly invasive growth. Because of their poor prognosis, new
      therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising
      strategy for treating cancer that incorporates both direct viral replication
      mediated and immune mediated mechanisms to kill tumor cells. C134 is a next
      generation Deltagamma134.5 oHSV-1 with improved intratumoral viral replication.
      It remains safe in the CNS environment by inducing early IFN signaling which
      restricts its replication in non-malignant cells. We sought to identify how C134
      performed in an immunocompetent tumor model that restricts its replication
      advantage over first generation viruses. To achieve this we identified tumors
      that have intact IFN signaling responses that restrict C134 and first generation
      virus replication similarly. Our results show that both viruses elicit a T cell
      mediated anti-tumor effect and improved animal survival but that subtle
      difference exist between the viruses effect on median survival despite equivalent
      in vivo viral replication. To further investigate this we examined the anti-tumor
      activity in immunodeficient mice and in syngeneic models with re-challenge. These
      studies show that the T cell response is integral to C134 replication independent
      anti-tumor response and that OV therapy elicits a durable and circulating anti
      tumor memory. The studies also show that repeated intratumoral administration can
      extend both OV anti-tumor effects and induce durable anti-tumor memory that is
      superior to tumor antigen exposure alone.

PMID- 29216508
TI  - Quantitative Biomarkers for Prediction of Epidermal Growth Factor Receptor
      Mutation in Non-Small Cell Lung Cancer.
AB  - OBJECTIVES: To predict epidermal growth factor receptor (EGFR) mutation status
      using quantitative radiomic biomarkers and representative clinical variables.
      METHODS: The study included 180 patients diagnosed as of non-small cell lung
      cancer (NSCLC) with their pre-therapy computed tomography (CT) scans. Using a
      radiomic method, 485 features that reflect the heterogeneity and phenotype of
      tumors were extracted. Afterwards, these radiomic features were used for
      predicting epidermal growth factor receptor (EGFR) mutation status by a least
      absolute shrinkage and selection operator (LASSO) based on multivariable logistic
      regression. As a result, we found that radiomic features have prognostic ability
      in EGFR mutation status prediction. In addition, we used radiomic nomogram and
      calibration curve to test the performance of the model. RESULTS: Multivariate
      analysis revealed that the radiomic features had the potential to build a
      prediction model for EGFR mutation. The area under the receiver operating
      characteristic curve (AUC) for the training cohort was 0.8618, and the AUC for
      the validation cohort was 0.8725, which were superior to prediction model that
      used clinical variables alone. CONCLUSION: Radiomic features are better
      predictors of EGFR mutation status than conventional semantic CT image features
      or clinical variables to help doctors to decide who need EGFR tyrosine kinase
      inhibitor (TKI) treatment.

PMID- 29216509
TI  - In vitro study on the joint hepatoxicity upon combined exposure of cadmium and
      BDE-209.
AB  - Joint toxicity is an important issue during the risk assessment of environmental
      pollutants. Contamination of heavy metals and persistent organic pollutants
      (POPs) under the environmental and biological settings poses substantial health
      risk to humans. Although previous studies demonstrated the co-occurrence of
      cadmium and decabrominated diphenyl ether (BDE-209) in environmental mediums,
      food chains and even human body, their potentially joint toxicities remain
      elusive thus far. Our investigation here with respect to the hepatotoxicity in
      vitro clearly demonstrated that combined exposure of cadmium and BDE-209
      aggravated the injuries in hepatocytes, which was evidenced by the additive
      effects on the induction of remarkable morphological alternations, LDH release,
      cell apoptosis and necrosis, impairment of mitochondrial activity and
      transmembrane potential. Enhanced ROS production was one of the mechanisms for
      cell apoptosis and death upon joint treatment. Additionally, more cadmium-treated
      cells underwent apoptosis than BDE-209-treated cells while more ROS was generated
      with BDE-209 treatment, indicating that other mechanisms might be involved in
      cadmium-induced apoptosis. Our results would be helpful for evaluating the joint
      hepatotoxicity upon combined exposure of cadmium and BDE-209 as well as
      investigating the underlying mechanisms.

PMID- 29216510
TI  - Evolution of virulence in the Mycobacterium tuberculosis complex.
AB  - Mycobacterium tuberculosis, the causative agent of human tuberculosis is one of
      the most widely spread human pathogens. It has succeeded to infect a quarter of
      the global human population by developing most sophisticated ways to circumvent
      innate and adaptive immune defences. This highly specialized, major human
      pathogen has evolved from a pool of ancestral environmental mycobacteria, whose
      extant representatives are known under the name of Mycobacterium canettii. Recent
      whole genome analyses in combination with different phenotypic screens have
      provided key insights into the evolution of M. tuberculosis and closely related
      members regrouped in the M. tuberculosis complex (MTBC). They have also
      elucidated novel virulence determinants that are essential for these obligate
      pathogens. In this review, we present the most recent evolutionary models of the
      MTBC and various factors that have contributed to the outstanding evolutionary
      success of the tuberculosis agent.

PMID- 29216511
TI  - Architecture and physicochemical characterization of Bacillus biofilm as a
      potential enzyme immobilization factory.
AB  - Biocatalysis for industrial application is based on the use of enzymes to perform
      complex transformations. However, these systems have some disadvantage related to
      the costs of the biocatalyst. In this work, an alternative strategy for producing
      green immobilized biocatalysts based on biofilm was developed.A study of the
      rheological behavior of the biofilm from Bacillus sp. Mcn4, as well as the
      determination of its composition, was carried out. The dynamic rheological
      measurements, viscosity (G") and elasticity (G') module, showed that the biofilm
      presents appreciable elastic components, which is a recognized property for
      enzymes immobilization. After the partial purification, the exopolysaccharidewas
      identified as a levan with a non-Newtonian behavior. Extracellular DNA with
      fragments between 10,000 and 1000bp was detected also in the biofilm, and amyloid
      protein in the extracellular matrix using a fluorescence technique was
      identified. Bacillus sp. Mcn4 biofilms were developed on different surfaces,
      being the most stable those developed on hydrophilic supports. The biofilm showed
      lipase activity suggesting the presence of constitutive lipases entrapped into
      the biofilm. Indeed, two enzymes with lipase activity were identified in native
      PAGE. These were used as biocatalysts, whose reuse showed a residual lipase
      activity after more than one cycle of catalysis. The components identified in the
      biofilm could be the main contributors of the rheological characteristic of this
      material, giving an exceptional environment to the lipase enzyme. Based on these
      findings, the current study proposes green and natural biopolymers matrix as
      support for the enzyme immobilization for industrial applications.

PMID- 29216512
TI  - Interaction between cereal beta-glucan and proteins in solution and at
      interfaces.
AB  - Cereal beta-glucan is well known for its beneficial health effects, such as
      lowering of blood cholesterol values and a reduced risk of coronary heart
      disease. These effects are often discussed in relation to the dissolution and
      aggregation behavior of the beta-glucan during human digestion. Furthermore,
      potential proteinaceous material present is believed to have an important impact
      on the formation of viscous slurries during digestion and might influence the
      aggregation behavior of the beta-glucan. Therefore, the interaction and
      aggregation behavior of a beta-glucan isolate (OBC90) with two different proteins
      (gliadin and whey protein) was investigated in solution at different pH with
      regards to kinetics of aggregation and protein/beta-glucan ratio and at
      interfaces. Aggregates were found at low pH and the aggregation and composition
      of aggregates seems to depend on the type of protein. Furthermore, phosphate was
      found at low concentrations in the beta-glucan, most likely being the reason for
      the net negative charge at pH<=4. Therefore, electrostatic interaction is
      suggested to play an important role for the aggregation between beta-glucan and
      proteins.

PMID- 29216513
TI  - A novel ultradeformable liposomes of Naringin for anti-inflammatory therapy.
AB  - Ultradeformable liposomes were formulated using naringin (NA), a flavanone
      glycoside, at different concentrations (3, 6 and 9mg/mL). Nanovesicles were small
      size (~100nm), regardless of the NA concentration used, and monodisperse
      (PI<0.30). All formulations showed a high entrapment efficiency (~88%) and a
      highly negative zeta potential (around -30mV). The selected formulations were
      highly biocompatible as confirmed by in vitro studies using 3T3 fibroblasts. In
      vitro assay showed that the amounts (%) of NA accumulated in the epidermis (~10%)
      could explain the anti-inflammatory properties of ultradeformable liposomes. In
      vivo studies confirmed the higher effectiveness of ultradeformable liposomes
      respect to betamethasone cream and NA dispersion in reducing skin inflammation in
      mice. Overall, it can conclude that NA ultradeformable liposomes can be
      considered as a promising formulation for the treatment of skin inflammatory
      diseases.

PMID- 29216514
TI  - Modulation of in vitro phagocytic uptake and immunogenicity potential of modified
      Herceptin(r)-conjugated PLGA-PEG nanoparticles for drug delivery.
AB  - There is an increasing interest in engineered nanoparticle (NP) conjugates for
      targeted and controlled drug delivery. However, the practical applications of
      these NP delivery vehicles remain constrained because of their reactivity with
      the body's immune system defenses resulting in undesirable off-target effects. In
      this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs
      conjugated to different quantities of the commercial antibody Herceptin(r) meant
      to target HER2-positive breast cancer cells were studied for their immune cell
      uptake and immunogenic properties (using murine macrophages and human dendritic
      cells). We further modified the Herceptin(r)-NP conjugates with short PEG linkers
      with an aim to increase their biocompatibility. The 50% Herceptin(r)-NP conjugate
      group with short PEG modification to Herceptin(r) showed the best reduction in
      immune cell uptake by 82% along with the reduction by >50% for proinflammatory
      cytokine response (TNF-alpha and IL-6). In conclusion, optimum Herceptin(r)
      coverage with improved hydrophilic profile results in reduced phagocytic uptake
      and immunogenicity of engineered NP-antibody conjugates, potentially minimizing
      their undesirable off-target effects as a drug delivery vehicle.

PMID- 29216515
TI  - Strontium incorporation improves the bone-forming ability of scaffolds derived
      from porcine bone.
AB  - Although heterogeneous bone scaffolds have shown potential in bone defect repair,
      their capability of aiding bone regeneration need to be further enhanced.
      Strontium, one important trace element in bone, has a well-known favorable effect
      on bone repair. Here a strontium containing scaffold (CPB/PCL/Sr) based on
      superficially porous calcined porcine bone (CPB) was obtained straightforwardly
      by sequential coating of SrCl2 and polycaprolactone (PCL). The basic
      characterization revealed that PCL coating could simultaneously improve the
      mechanical properties and, more importantly, restrain strontium release.
      Moreover, in vitro behaviors of human MSCs on CPB, CPB/PCL, and CPB/PCL/Sr were
      studied in detail. The comprehensive results of proliferation, osteogenic gene
      expression, ALP staining, and ALP activity demonstrated that PCL coating slightly
      impaired the bone repair potential of CPB. In contrast, CPB/PCL/Sr better
      supported the osteogenic differentiation of MSCs than CPB,highlighting the role
      of strontium. The in vivo test confirmed a better new bone formation of
      CPB/PCL/Sr than CPB and CPB/PCL. These results verified the superiority of
      incorporating strontium to improve the bone-forming ability of CPB, offering a
      promising alternative for bone defect repair.

PMID- 29216516
TI  - ATR-FTIR investigation of mechanisms of Bacillus subtilis adhesion onto variable-
      and constant-charge soil colloids.
AB  - The primary objective of this study was to determine the capacity and the
      mechanisms of adhesion of Bacillus subtilis onto variable- and constant-charge
      soil colloids. The adhesion process was investigated using in situ attenuated
      total reflectance (ATR)-Fourier transform infrared spectroscopy (FTIR), zeta
      potential, and batch adhesion experiments. The maximum adhesion capacity of B.
      subtilis on the colloids of Oxisol, Ultisol, and Alfisol reached 699.17, 462.56,
      and 258.82mgg-1, respectively. B. subtilis adhesion to all three soil colloids
      decreased as the suspension pH increased from 3 to 8. Saturation coverage and
      adhesion rate constant values were calculated with the pseudo-first-order
      kinetics equation using the absorbance at 1548cm-1. Both values were highest for
      Oxisol, followed by Ultisol, and lowest for Alfisol. These observations are
      consistent with the surface charges of these soil colloids. A larger positive
      charge on variable-charge soils (Oxisol and Ultisol) increased B. subtilis
      adhesion relative to that of constant-charge soil (Alfisol). This is in agreement
      with the interaction energy between B. subtilis and soil colloids, which was
      calculated using the Derjaguin-Landau-Verwey-Overbeek theory. As revealed by ATR
      FTIR spectroscopy, chemical bonds formed by protein, phosphate, and COOH groups
      on B. subtilis, as well as iron and aluminum hydroxyl groups in soil, contributed
      to B. subtilis adhesion to soil colloids. Therefore, chemical bond formation and
      electrostatic interaction are two major mechanisms of B. subtilis adhesion onto
      soil colloids.

PMID- 29216517
TI  - GO-AgCl/Ag nanocomposites with enhanced visible light-driven catalytic properties
      for antibacterial and biofilm-disrupting applications.
AB  - Nanomaterials with visible light-driven photocatalytic activity have attracted
      much attention due to their excellent abilities in degradation of various organic
      pollutants as well as inactivating bacteria. Herein, graphene oxide (GO)
      enwrapped silver chloride/silver (AgCl/Ag) nanocomposites with high visible light
      absorption were designed and fabricated as efficient antibacterial agents. AgCl
      NPs were synthesized in the presence of GO first and Ag NPs were coated on AgCl
      surface by heat reduction to form GO-AgCl/Ag nanocomposites. The as prepared
      nanocomposites revealed improved stability, higher absorption properties in the
      visible light region. The enhanced antibacterial activity was observed by
      quantification of colony forming units (CFU) and morphological changes of
      bacteria. The antibacterial mechanism of GO-AgCl/Ag was also investigated by
      evaluating membrane permeability and ROS level. Moreover, GO-AgCl/Ag composites
      can eliminate bacterial biofilms more efficiently under visible light
      irradiation. Our results provide new insights into the design of new
      multifunctional systems for antibacterial applications.

PMID- 29216519
TI  - Mine is better than yours: Investigating the ownership effect in children with
      autism spectrum disorder and typically developing children.
AB  - Ownership has a unique and privileged influence on human psychology. Typically
      developing (TD) children judge their objects to be more desirable and valuable
      than similar objects belonging to others. This 'ownership effect' is due to
      processing one's property in relation to 'the self'. Here we explore whether
      children with autism spectrum disorder (ASD) - a population with impaired self
      understanding - prefer and over-value property due to ownership. In Experiment 1,
      we discovered that children with ASD did not favour a randomly endowed toy and
      frequently traded for a different object. By contrast, TD children showed a clear
      preference for their randomly endowed toy and traded infrequently. Both
      populations also demonstrated highly-accurate tracking of owner-object
      relationships. Experiment 2 showed that both TD children and children with ASD
      over-value their toys if they are self-selected and different from other-owned
      toys. Unlike TD children, children with ASD did not over-value their toys in
      comparison to non-owned identical copies. This finding was replicated in
      Experiment 3, which also established that mere ownership elicited over-valuation
      of randomly endowed property in TD children. However, children with ASD did not
      consistently regard their randomly endowed toys as the most valuable, and
      evaluated property irrespective of ownership. Our findings show that mere
      ownership increases preferences and valuations for self-owned property in TD
      children, but not children with ASD. We propose that deficits in self
      understanding may diminish ownership effects in ASD, eliciting a more
      economically-rational strategy that prioritises material qualities (e.g. what a
      toy is) rather than whom it belongs to.

PMID- 29216518
TI  - Expanding horizons: new roles for non-canonical RNA-binding proteins in cancer.
AB  - Cancer development involves the stepwise accumulation of genetic lesions that
      overcome the normal regulatory pathways that prevent unconstrained cell division
      and tissue growth. Identification of the genetic changes that cause cancer has
      long been the subject of intensive study, leading to the identification of
      several RNA-binding proteins (RBPs) linked to cancer. Cross-reference of the
      complement of RBPs recently identified by RNA interactome capture with cancer
      associated genes and biological processes led to the identification of a set of
      411 proteins with potential implications in cancer biology. These involve a broad
      spectrum of cellular processes including response to stress, metabolism and cell
      adhesion. Future studies should aim to understand these proteins and their
      connection to cancer from an RNA-centred perspective, holding the promise of new
      mechanistic understanding of cancer formation and novel approaches to diagnosis
      and treatment.

PMID- 29216520
TI  - Green pastures: Do US real estate prices respond to population health?
AB  - We investigate whether communities with improving population health will
      subsequently experience rising real estate prices. Home price indices (HPIs) for
      371 MSAs from 1990 to 2010 are regressed against life-expectancy five years
      prior. HPIs come from the Federal Housing Finance Agency. Life expectancy
      estimates come from the Institute of Health Metrics. Our analysis uses random and
      fixed effect models with a comprehensive set of controls. Life expectancy
      predicted increases in the HPI controlling for potential confounders. We found
      that, this effect varied spatially. Communities that invest their revenue from
      property taxes in public health infrastructure could benefit from a virtuous
      cycle of better health leading to higher property values. Communities that do not
      invest in health could enter vicious cycles and this could widen geospatial
      health and wealth disparities.

PMID- 29216521
TI  - The use of palliative medications before death from prostate cancer: Swedish
      population-based study with a comparative overview of European data.
AB  - BACKGROUND: Symptoms of terminal cancer have previously been reported as
      undertreated. The aim of this study was to assess the use of palliative
      medications before death from prostate cancer. METHODS: This Swedish register
      study included men who died from 2009 to 2012 with prostate cancer as the
      underlying cause of death. We assessed the proportion who collected a
      prescription of androgen deprivation therapy, non-steroidal anti-inflammatory
      drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and
      sedative-hypnotics and the differences in treatment related to age, time since
      diagnosis, educational level, close relatives and comorbidities. Data were
      collected from 3 years before death from prostate cancer. RESULTS: We included
      8326 men. The proportion who received opioids increased from 30% to 72% during
      the last year of life, and 67% received a strong opioid at the time of death.
      Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and
      sedative-hypnotics from 21% to 33%. Men without close relatives and older men had
      lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence
      interval [CI]: 0.47-0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI:
      0.66-0.92 for unmarried without children versus married with children).
      CONCLUSION: Our results represent robust epidemiological data from Sweden for
      comparison of palliative care quality between countries. The findings indicate
      that men without close relatives and older men are disadvantaged with respect to
      the treatment of cancer pain and need closer attention from health care providers
      and highlight the importance to identify psychological distress in terminal
      prostate cancer.

PMID- 29216522
TI  - Case of urethral duplication seen by voiding urosonography.
AB  - A 3-month-old premature male infant with imperforate anus and hypospadias
      underwent contrast-enhanced voiding urosonography (ceVUS) followed by voiding
      cystourethrography (VCUG). Images from the ceVUS demonstrated a distinct
      linearity arising dorsally from the posterior urethra that partially opacified
      with contrast. VCUG confirmed a urethral duplication. To our knowledge, this
      exceedingly rare anomaly has yet to be reported by ceVUS.

PMID- 29216523
TI  - Use of synthetic stimulants and hallucinogens in a cohort of electronic dance
      music festival attendees.
AB  - Novel psychoactive substances (NPS), often characterized as unregulated
      psychoactive compounds designed to circumvent existing legislation, have become
      mainstream on the illicit drug market. Because of their physical and mind
      altering properties, NPS may be deliberately or inadvertently ingested at
      electronic dance music (EDM) festivals to enhance the attendees' appreciation of
      the music and overall experience. Their widespread use at EDM festivals have been
      well documented and several adverse events and fatalities associated with NPS
      ingestion have been reported in the United States. The diversity and rapid
      turnover in the prevalence of any particular NPS at any given point of time has
      created several challenges for public health officials, law enforcement, and
      forensic science communities. Epidemiological studies are often published long
      after drugs have cycled through the peak of their popularity with users and the
      scope of testing frequently failing to detect, identify or report the most
      recently available drugs. The aims of the study included discovering emerging
      NPS, ascertaining their overall prevalence and determining patterns of use and
      trends within this targeted population. Over the course of two years, biological
      samples were collected from 396 (126 blood samples; 227 urine samples; and 384
      oral fluid samples) EDM festival attendees. Additionally, survey data regarding
      prescription and recreational drug use within the last week were collected with
      follow-up questions related to what substance(s) the person had ingested, amount
      taken, when the substance was last taken and perceived effects. All biological
      samples were screened and subsequently confirmed and/or quantified, when
      appropriate. In response to survey questions, 72% of the participants reported
      using a recreational drug or medicinal substance within the last week. Users most
      commonly reported using marijuana and alcohol, followed by "Molly" and cocaine.
      Of the 396 individuals tested, approximately 75% of the population was positive
      in at least one biological specimen for drugs and/or alcohol. Of those positive
      samples, 36% were confirmed to contain one or more NPS and/or 3,4-methylenedioxy
      methamphetamine (MDMA). High rates of turnover and spikes in popularity related
      to NPS are supported by samples confirming positive for alpha-PVP in 2014,
      however, one year later not a single case was positive for alpha-PVP, and instead
      increasing numbers of subjects were positive for ethylone.

PMID- 29216524
TI  - Multiple fatalities in the North of England associated with synthetic fentanyl
      analogue exposure: Detection and quantitation a case series from early 2017.
AB  - BACKGROUND: Synthetic fentanyl analogues are highly potent opioid drugs which
      have no pharmaceutical use in humans. We detected the synthetic fentanyl
      analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl,
      and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have
      been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK).
      METHODS: Cases in which the history clearly stated drug use but where a post
      mortem blood morphine concentration was lower than would be expected to explain
      the sudden death, were referred for further analysis by high resolution accurate
      mass (HRAM) mass spectrometry. RESULTS: 25 post mortem cases in which synthetic
      fentanyl analogues were implicated in the cause of death were reported from
      January to May 2017. No cases were seen in June 2017. The age range was 21-54
      years and 22 were male. There was a history of heroin use, or markers of heroin
      use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were
      detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13
      cases, with the remaining 5 cases having only carfentanil present. Synthetic
      fentanyl analogues were detected in combination with other drugs in all cases.
      Significant concentrations of ethanol were detected in only 2 cases. The
      concentration range of carfentanil in blood was 90-4004pg/mL. Of note, the 3
      cases in which ante mortem carfentanil was quantified ranged from 21 to 98pg/mL.
      In all cases, death was attributed to combined central nervous system depression.
      CONCLUSIONS: This paper highlights a new and rapid emergence of these drugs into
      the UK illicit drug arena. Synthetic fentanyl analogues represent a significant
      challenge both analytically and clinically within the groups who misuse drugs. It
      is worthwhile considering the possibility of the presence of these drugs in cases
      in which a toxicological cause of death is not apparent analytically but there is
      a history of drug use and circumstantial evidence exists to support a drug
      related death as the most likely cause. It may be that synthetic fentanyl
      analogues should be screened for routinely to avoid reporting any false negative
      results, but the cost implications and viability of this have not been fully
      evaluated.

PMID- 29216525
TI  - High-refined carbohydrate diet promotes detrimental effects on alveolar bone and
      femur microarchitecture.
AB  - : The impact of high-refined carbohydrate (HC) diet on fat accumulation,
      adipokines secretion and systemic inflammation is well described. However, it
      remains unclear whether these processes affect bone remodeling. OBJECTIVE: To
      investigate the effects of HC diet in the alveolar bone and femur parameters.
      METHODS: BalbC mice were fed with conventional chow or HC diet for 12 weeks.
      After experimental time maxillae, femur, blood and white adipose tissue samples
      were collected. RESULTS: The animals feed with HC diet exhibited considerable
      increase of adiposity index and adipose tissue levels of TNF-alpha, IL-6, IL-10,
      IL-1beta, TGF-beta and leptin. Microtomography analysis of maxillary bone
      revealed horizontal alveolar bone loss and disruption of trabecular bone in mice
      feed with HC diet. These deleterious effects were correlated with a disturbance
      in bone cells and an augmented expression of Rankl/Opg ratio. Consistently,
      similar effects were observed in femurs, which also exhibited a reduction in bone
      maximum load and stiffness. CONCLUSION: Our data indicates that HC diet
      consumption disrupts bone remodeling process, favoring bone loss. Underlying
      mechanisms relies on fat tissue accumulation and also in systemic and local
      inflammation.

PMID- 29216526
TI  - Dickkopf-1 may regulate bone coupling by attenuating wnt/beta-catenin signaling
      in chronic apical periodontitis.
AB  - OBJECTIVE: Alveolar bone loss is a common outcome of chronic apical
      periodontitis. In this study, we investigated the involvement of the Dickkopf-1
      Wnt/beta-catenin signaling pathway in the attenuation of osteogenic
      differentiation induced by Escherichia coli lipopolysaccharide, and we evaluated
      the use of Dickkopf-1 inhibitor and Dickkopf-1 recombinant protein to reverse
      bone loss in different phases of osteogenic differentiation. METHODS: MC3T3-E1
      cells grown in osteogenic medium were treated with Escherichia coli
      lipopolysaccharide for 24h during osteogenic induction on days 0, 1, 7, 14 and
      21. Dickkopf-1 siRNA was added on days 0 and 1, and Dickkopf-1 recombinant was
      added on days 7, 14, and 21. Quantitative real-time PCR, Western blotting and
      alkaline phosphatase activity assays were performed to measure osteogenic marker
      expression and Wnt/beta-catenin signaling. A rat apical periodontitis model was
      used to further evaluate the function of Dickkopf-1 in relation to bone loss.
      RESULTS: MC3T3-E1 cells treated with Escherichia coli lipopolysaccharide showed
      decreased mRNA expression of osteogenic markers. Wnt/beta-catenin signaling was
      also inhibited, and Dickkopf-1 showed corresponding variations as quantified by
      Western blotting. Using Dickkopf-1 inhibitor or Dickkopf-1 recombinant protein at
      different phases of osteogenic differentiation in vitro partially reversed the
      decrease in osteogenic marker expression. The rat apical periodontitis model
      indicated that the Dickkopf-1 inhibitor could restore bone loss in the periapical
      area in vivo. CONCLUSIONS: Dickkopf-1 may play a key regulatory role in
      determining the outcome for bone in inflammatory environments, and modulating the
      Wnt/beta-catenin signaling pathway via Dickkopf-1 inhibitor or recombinant
      protein may provide a potential therapeutic option to prevent bone destruction in
      endodontic disease.

PMID- 29216527
TI  - Laparoscopic management of a drain site evisceration of the vermiform appendix, a
      case report.
AB  - INTRODUCTION: Peritoneal cavity drainage is not riskless and several publications
      reported drain induced complications. However, till this day, abdominal drainage
      is still a subject of divergence between necessity and usual operative practice.
      We describe in this publication an exceptional complication of drainage, which is
      the drain site evisceration of the appendix. CASE PRESENTATION: We report the
      case of a 47-years-old patient, initially operated for perforated ulcer
      peritonitis, in whom an evisceration occured 48h after the removal of an
      intraperitoneal drain placed in the Douglas pouch, the physical examination
      predicated the presence of a herniated omentum fringe, as a precaution a
      laparoscopic exploration was performed and revealed that the eviscerated organ
      was the vermiform appendix, then a two trocars appendectomy was performed and the
      orifice of the evisceration was safely closed. DISCUSSION: Since the first
      description in 1995, only seven cases were reported in the literature, we propose
      a new management of the drain site evisceration of the appendix, including
      laparoscopic exploration, and both side control of the drain site defect closure,
      our technique seems safer. CONCLUSION: The laparoscopic approaches must have a
      place in the management of the drain site eviscerations.

PMID- 29216528
TI  - Triple primary malignancies in a patient with colorectal adenocarcinoma: A case
      report.
AB  - INTRODUCTION: While colorectal carcinoma is one of the most commonly diagnosed
      malignancies, its synchronous occurrence with other primary malignancies is rare.
      PRESENTATION OF CASE: In this case, we describe the diagnosis and surgical
      intervention of a 55-year-old male patient who was found to have colonic
      adenocarcinoma at the hepatic flexure, right renal urothelial carcinoma, and
      malignant mesothelioma. DISCUSSION: None of the previous studies reported these
      three distinct types of cancer, even in those patients with Lynch Syndrome. To
      the best of our knowledge, this is the first report of such case. The etiology
      and pathogenesis of multiple primary malignancies are complex. Common genetic and
      environmental risk factors that were found in different cancers might increase
      the risk of multiple primary malignancies. CONCLUSION: The use of genetic testing
      and preoperative imaging studies should be considered to be invaluable tools for
      detecting synchronous malignancies. Practicing physicians should pay more
      attention to the risk of simultaneous separate primary malignancies.

PMID- 29216529
TI  - Sessile serrated adenoma/polyp leading to acute appendicitis with multiple
      pyogenic liver abscesses: A case report.
AB  - INTRODUCTION: Although appendicitis is a common disease, appendicitis concurrent
      with liver abscesses and sessile serrated adenoma/polyp (SSA/P) is rare.
      PRESENTATION OF CASE: A 69-year-old man presented with symptoms of abdominal pain
      and fever. Computed tomography (CT) revealed multiple liver abscesses and an
      enlarged appendix with a pseudotumoral appearance, which suggested acute
      appendicitis. In the emergency operation, ileocecal resection was performed for
      the perforated appendicitis with an inflammatory mass in the ileocecum. On
      macroscopic examination, the torose lesion was localized at next to the
      appendiceal orifice. The tumor was diagnosed as SSA/P based on the microscopic
      finding. The postoperative course was uneventful, and the liver abscesses were
      cured by antibiotic therapy. The patient was discharged 17days after the surgery.
      DISCUSSION: In this case, SSA/P localization at next to the appendiceal orifice
      was suggested as the cause of the perforated appendicitis with multiple liver
      abscesses. The patient was successfully treated with a combination of surgery and
      antibiotic therapy. CONCLUSION: This is the first reported case of a patient with
      SSA/P that led to acute appendicitis with multiple pyogenic liver abscesses.

PMID- 29216530
TI  - Brain angiometastasis from a non-seminomatous germ cell tumor: A case report.
AB  - INTRODUCTION: Brain metastasis from non-seminomatous germ cell tumors (NSGCT) is
      rare. Herein, we describe the second reported case of brain metastasis from a
      NSGCT with high-flow arteriovenous (AV) shunts, and propose a novel surgical
      treatment plan. CLINICAL CASE: The patient was a 34-year-old male who presented
      with hemiparesis and hemianesthesia. Magnetic resonance angiography revealed
      three vascular lesions with afferent vessels and efferent vessels. Angiography
      displayed two high-flow AV shunts. During angiography, the patient experienced
      sudden neurological deterioration and consequently underwent surgery. During
      surgery, a lesion with large AV shunts was observed, with arterialized drainage
      veins, pedicled arterial vessels affluent to the nidus, and an absent pial plane.
      The surgical technique was adapted to lesion morphology using special bipolar
      forceps. Histological and immunohistochemical tests confirmed that the lesion was
      a NSGCT. DISCUSSION: NSGCTs are clinically more aggressive than seminomas.
      Lesions with an AV shunt and glioma combination are designated as angiogliomas.
      Therefore, we termed the lesion in the present case as an "angiometastasis,"
      which was formed from numerous AV shunts. The use of presurgical embolization has
      been reported to improve long-term survival in patients with intra-axial
      hypervascular tumors with AV shunts. CONCLUSION: We here propose a novel strategy
      for the management of hypervascular brain metastasis from NSGC, consisting of
      angiography, tumor embolization, and the use of an angiometastatic surgical
      technique with special bipolar forceps. This case report may help neurosurgeons
      make better surgical decisions in the management of highly vascularized brain
      metastasis.

PMID- 29216531
TI  - Living donor liver transplantation for adult Budd Chiari syndrome - Resection
      without replacement of retrohepatic IVC: A case report.
AB  - INTRODUCTION: Suprahepatic caval resection and replacement of inferior vena cava
      (IVC) is standard procedure in deceased donor liver transplantation for patients
      with Budd-Chiari syndrome (BCS). However, replacement of IVC in living donor
      liver transplantation (LDLT) is difficult. We report a case of BCS successfully
      treated by LDLT without replacement of IVC. PRESENTATION OF CASE: A 52-years-old
      female with a primary BCS due to IVC thrombosis. A vena cava (VC) stent placed
      after angioplasty without improvement of the hepatic, portal venous flow and
      liver functions, Transjugular intrahepatic portosystemic shunt was considered and
      the patient had a rapid deterioration and increased ascites. The patient was
      scheduled for living donor liver transplantation (LDLT). Her Child-Paugh and MELD
      scores were 11, 18, respectively at time of transplantation. Left lobe was
      obtained from her son. Preservation of the native suprarenal IVC was impossible
      due to massive fibrosis and thrombosed. The suprahepatic IVC was also fibrotic
      and unsuitable for anastomosis with hepatic vein. The retrohepatic IVC resected
      include suprahepatic IVC together with the liver. The supradiaphragmatic IVC was
      reached and encircled through opening the diaphragm around the IVC and a vascular
      clamp applied on the right atrium with subsequent anastomosis with hepatic vein
      of the graft. The hemodynamic stability of the patient was maintained throughout
      the operation without IVC replacement due to developed collateral vessels.
      CONCLUSION: Patients with Budd-Chiari syndrome with obstructive IVC are
      successfully treated with living donor liver transplantation without replacement
      of IVC.

PMID- 29216532
TI  - Spontaneous regression of pancreatic cancer: A case report and literature review.
AB  - INTRODUCTION: Spontaneous regression of cancer is defined as the partial or
      complete disappearance of malignant disease without treatment, or in the presence
      of therapy that is deemed inadequate to exert an influence on malignant disease,
      as composed by Tilden Everson and Warren Cole in the 1960s. It has been a topic
      of major interest in the field of medical and surgical oncology. It is poorly
      understood and scantily documented. Factors associated and postulated
      pathogeneses are at best, hypothetical. PRESENTATION OF CASE: We report a case of
      spontaneous resolution of a head of pancreas carcinoma in a 77-year-old gentleman
      after a myocardial infarction event delayed planned surgery. DISCUSSION: A
      literature review of previously reported cases of spontaneous regression of
      pancreatic cancer was performed. The possible predisposing factors to spontaneous
      regression of pancreatic and other forms of malignancies was reviewed.
      CONCLUSION: This is a novel case of spontaneous regression of pancreatic
      carcinoma after an episode of myocardial infarction. The pathophysiology to
      spontaneous resolution of cancer is not well understood, may be multifactorial
      and requires further study.

PMID- 29216533
TI  - Assessing the zoonotic potential of arboviruses of African origin.
AB  - Several African arboviruses have emerged over the past decade in new regions
      where they caused major outbreaks in humans and/or animals including West Nile
      virus, Chikungunya virus and Zika virus. This raise questions regarding the
      importance of less known zoonotic arboviruses in local epidemics in Africa and
      their potential to emerge internationally. Syndromic surveillance in animals may
      serve as an early warning system to detect zoonotic arbovirus outbreaks. Rift
      Valley fever and Wesselsbronvirus are for example associated with abortion storms
      in livestock while West Nile-virus, Shuni virus and Middelburg virus causes
      neurological disease outbreaks in horses and other animals. Death in birds may
      signal Bagaza virus and Usutu virus outbreaks. This short review summarise data
      on less known arboviruses with zoonotic potential in Africa.

PMID- 29216534
TI  - Thrombolytic therapy based on fucoidan-functionalized polymer nanoparticles
      targeting P-selectin.
AB  - Injection of recombinant tissue plasminogen activator (rt-PA) is the standard
      drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and
      limited efficiency even at high doses. Polysaccharide-poly(isobutylcyanoacrylate)
      nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to
      accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin
      expressed by activated platelets in the thrombus. Solid spherical fluorescent
      nanoparticles with a hydrodynamic diameter of 136 +/- 4 nm were synthesized by
      redox radical emulsion polymerization. The clinical rt-PA formulation was
      successfully loaded by adsorption on aminated nanoparticles and able to be
      released in vitro. We validated the in vitro fibrinolytic activity and binding
      under flow to both recombinant P-selectin and activated platelet aggregates. The
      thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by
      monitoring the platelet density with intravital microscopy. This study supports
      the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This
      work establishes the proof-of-concept of fucoidan-based carriers for targeted
      thrombolysis.

PMID- 29216535
TI  - Nanoantagonists with nanophase-segregated surfaces for improved cancer
      immunotherapy.
AB  - The blockade of PD-1/PD-L1 interaction by peptide antagonists can unleash and
      enhance pre-existing anti-cancer immune responses of T cells to eradicate cancer
      cells. However, low proteolytic stability is the "Achilles' Heel" of peptides.
      Here, we first report a nanoantagonist with a physiological temperature sensitive
      nanophase-segregated surface that exhibits significantly enhanced blood
      circulation, peptide stability and PD-L1 immune checkpoint blockade efficacy.
      Thermosensitive polymers with different phase transition temperatures (Tt) are
      used to form the nanophase-segregated surface on an Au nanorod core. Importantly,
      the nanophase-segregated surface aids the nanoantagonist to resist protein
      adsorption and enhance the systemic stability of the linked peptides. Finally,
      the as-designed nanoantagonist effectively blocks PD-1/PD-L1 interaction in vitro
      and in vivo, enhances the pre-existing CD8+ T cell tumor destruction capability
      and inhibits tumor growth. This study offers a new strategy for designing nano
      formulations for cancer immunotherapy.

PMID- 29216536
TI  - Myelodysplastic syndromes without peripheral monocytosis but with evidence of
      marrow monocytosis share clinical and molecular characteristics with CMML.
AB  - MDS patients may present with monocytic marrow proliferation not fulfilling
      criteria for CMML. We analyzed MDS patients with or without a marrow monocytic
      proliferation by following up the amount of monocytic proliferation and
      characterizing their molecular profile. 315 MDS patients of Duesseldorf MDS
      registry were divided into two groups: A) 183 patients with monocytic esterase
      positive cells in marrow and monocytes between 101 and 900/MUl in blood and B)
      132 patients without monocytic esterase positive cells in marrow and monocytes in
      blood <=100/MUl. Twenty patients of each group were screened with regard to
      ASXL1, TET2, RUNX1, SETBP1, NRAS, and SRSF2 using Illumina myeloid panel. Group A
      patients were older, had significantly higher WBC, hemoglobin levels, neutrophils
      and platelets. CMML evolution rates were 4.9% and 1.5%, respectively (p=n.s.).
      TET2, NRAS and SRFS2 mutation frequencies were higher in group A and four
      patients had coexisting TET2 and SRFS2 mutation, which was shown to be
      characteristic but not specific for CMML. MDS patients with marrow monocytic
      proliferation have a more CMML-like pheno- and genotype and develop CMML more
      often. Those patients could potentially be very early stages of CMML or represent
      a CMML-like myeloid neoplasma with marrow adherence of the monocytic cell
      population.

PMID- 29216537
TI  - Pneumocephalus and seizures following combined spinal-epidural for labor.

PMID- 29216538
TI  - TIP60 contributes to porcine embryonic development by regulating DNA damage
      response.
AB  - The acetyltransferase TIP60 (also known as Kat5) is a member of the MYST family
      of histone acetyltransferases and was initially identified as a cellular protein.
      TIP60 acetylates histone and non-histone proteins and is involved in diverse
      biological processes, including apoptosis, cell cycle, and DNA damage responses.
      In this study, a specific inhibitor of TIP60 was used to detect the function of
      TIP60 in porcine parthenogenetic embryos. The results showed that TIP60
      inhibition impaired porcine parthenogenetic embryonic development. The mechanism
      of TIP60 was also determined. We found that the TIP60 inhibition impaired
      embryonic development by ROS induced DNA damage, as demonstrated by the number of
      gammaH2A in the nuclei. TIP60 inhibition triggered DNA damage through the
      regulation of p53-p21 pathway and TIP60 played a role in DNA repair. TIP60
      inhibition decreased the efficiency of DNA repair by regulating 53BP1-dependent
      repair after DNA damage. Inhibition of TIP60 also increased the adaptive
      response, autophagy, by modulating LC3. Therefore, TIP60 plays a role in early
      porcine parthenogenetic embryonic development by regulating DNA damage and
      repair.

PMID- 29216539
TI  - Influence of extracellular environment on the motility and structural properties
      of spermatozoa collected from hormonally stimulated Panamanian Golden Frog
      (Atelopus zeteki).
AB  - A better understanding of the factors influencing the biology of amphibian
      spermatozoa after release from the testis is a prerequisite to the development of
      sperm preservation methods. The objective of the study was to determine the
      effect of extracellular conditions (exposure to water and different temperatures)
      over time on the sperm motility and structural properties (including morphology
      and DNA integrity) collected from hormonally stimulated Atelopus zeteki.
      Following intraperitoneal injection of gonadotropin-releasing hormone agonist
      (des-Gly10, D-Ala6, Pro-NHEt9 GnRH; 4 MUg/g of body weight), human chorionic
      gonadotropin (hCG, 10 IU/gbw), or AmphiplexTM (0.4 MUg/gbw GnRH-A + 10 MUg/gbw
      metoclopramide hydrochloride), spermic urine samples from 27 males were collected
      and analyzed for sperm motility, morphology and DNA integrity while maintained at
      room temperature (23  degrees C), 4  degrees C, or diluted in water (hypo-osmotic
      environment) over a period of 46 min post-collection. Percentages of sperm
      motility and forward progressive motility remained high (>60%) when spermic urine
      was kept at room temperature or at 4  degrees C for 46 min regardless of the
      hormonal stimulation method. Dilution in water at room temperature greatly
      reduced the percentage of motile spermatozoa and forward progression (<50%) as
      well as DNA integrity (32.8% of intact cells) after 23 min while morphology did
      not differ (30.4% of normal cells), regardless of the hormone stimulation. This
      is the first systematic study on the effect of extracellular environment over
      time on A. zeteki sperm quality. This will contribute to the development of sperm
      handling protocols and reproductive technologies for this and other endangered
      Atelopus species.

PMID- 29216540
TI  - Longitudinal study of retinal nerve fiber layer thickness changes in a multiple
      sclerosis patients cohort: A long term 5 year follow-up.
AB  - PURPOSE: To analyze the changes in retinal nerve fiber layer (RNFL) in eyes with
      and without prior history of optic neuritis (ON) of patients with multiple
      sclerosis (MS) after a 5-year time period (2010-2015) using optical coherence
      tomography. METHODS: The RNFL thickness of 114 eyes of 57 MS patients and 40 eyes
      of 20 healthy subjects were measured in year 2010 and year 2015. Measurements
      were made separately in twelve sectors around the optic nerve head. Statistical
      comparisons were made with the obtained data. RESULTS: Progressive RNFL thinning
      occurs with time in both MS patients (regardless the eye had history of ON or
      not) and in normal subjects. The baseline mean RNFL thickness in ON eyes of MS
      patients (year 2010) was 74.2 +/- 15.7um and five years later was 68.7 +/-
      12.2um. The baseline mean RNFL thickness in eyes without ON of MS patients was
      90.0 +/- 11.1um and 84.7 +/- 10.3um five years later. The median RNFL thickness
      reduction was 3.5um for ON eyes, 4.7um for eyes without ON, and 2.2um for control
      eyes. The RNFL thickness reduction rate was similar in eyes with history of ON
      that in those with no history of ON. On the contrary, the MS group had a
      significantly higher rate of reduction than the control group. CONCLUSIONS: MS
      patients have thinner RNFL than normal controls, regardless their eyes had past
      episodes of ON or not. Eyes of MS patients lose their axons in a similar fashion
      regardless they had history of ON or not. Although ON causes RNFL loss, once
      resolved it does not influence the rate of RNFL loss in MS patients.

PMID- 29216541
TI  - Texting while walking differently alters gait patterns in people with multiple
      sclerosis and healthy individuals.
AB  - BACKGROUND: In recent times, increasing safety concerns have been associated with
      the use of mobile phones by pedestrians. In particular, texting has been shown to
      significantly alter gait patterns. However, no specific investigations have been
      performed on people with Multiple Sclerosis (pwMS), who are already characterized
      by gait dysfunctions caused by the disease. OBJECTIVE: To assess the existence of
      possible alterations in spatio-temporal parameters of gait in pwMS when
      simultaneously texting on a smartphone and walking. METHODS: Fifty-four pwMS
      (mean age 40.5 +/- 10.5) and 40 age-matched unaffected individuals were tested in
      two conditions: walking, and walking while texting on a smartphone. Spatio
      temporal parameters of gait were assessed using a wearable accelerometer located
      on the lower back. RESULTS: Texting induces reduction of gait speed, stride
      length and cadence in both groups, but such changes were smaller in magnitude in
      pwMS. An increase of stance and double support and reduction of swing phase were
      observed in pwMS only. CONCLUSIONS: Texting alters gait patterns of pwMS
      differently from unaffected individuals, probably due to a different
      prioritization of the task, which appears to take into account the motor and
      sensory impairments associated with the disease by favoring the motor task.

PMID- 29216543
TI  - A socio-economic hypothesis for lower birth sex ratios at racial, national and
      global levels.
AB  - The sex ratio at birth may be depressed by a variety of events or conditions due
      to an excess of male foetal losses. Evidence is accumulating that observed
      differences in this ratio between races, nations and even at regional global
      level, may be due to socio-economic stress. This review summarises findings
      pertaining to Blacks in the United States, and to a global United Nations
      dataset, as well as to other smaller studies. Extant evidence reinforces the
      theory that chronic socio-economic stress may be the reason for a lower birth sex
      ratio at racial, national and global levels. While innate periconceptual and
      gestational (e.g. hormonal) racial differences have been cited as possible causes
      for these M/T differences, this may be a mechanism/pathway and not the actual
      cause for lower M/T. Stress may, however, act by using hormonal pathways to
      effect the observed M/T disparities.

PMID- 29216542
TI  - Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid
      body development from mouse embryonic stem cells.
AB  - Heme oxygenase (HO)-1 is an inducible stress response protein and well known to
      protect cells and tissues against injury. Despite its important function in
      cytoprotection against physiological stress, the role of HO-1 in embryonic stem
      cell (ESC) differentiation remains largely unknown. We showed previously that
      induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant
      stress-induced cell death and more prone to lose pluripotent markers upon LIF
      withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out
      the controversy of potential gene flaws in iPS cells, we derived and established
      mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3
      and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation
      model, we showed that at an early time point during EB development, an absence of
      HO-1 led to enhanced ROS level, concomitant with increased expressions of master
      mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical
      smooth muscle cell (SMC) transcription factor serum response factor and its
      coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2
      in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not
      only mediates mesendoderm differentiation of mouse ESCs but also SMC development.
      Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC
      regulators, leading to accelerated and enhanced SMC marker SM alpha-actin
      expression. Our results reveal a previously unrecognized function of HO-1 in
      regulating SMC gene expressions during ESC-EB development. More importantly, our
      findings may provide a novel strategy in enhancing ESC differentiation toward SMC
      lineage.

PMID- 29216544
TI  - Crystal structures of murine and human Histamine-Releasing Factor (HRF/TCTP) and
      a model for HRF dimerisation in mast cell activation.
AB  - In allergic disease, mast cell activation is conventionally triggered by allergen
      mediated cross-linking of receptor-bound IgE on the cell surface. In addition to
      its diverse range of intracellular roles in apoptosis, cell proliferation and
      cancer, Histamine-Releasing Factor (HRF) also activates mast cells and basophils.
      A subset of IgE antibodies bind HRF through their Fab regions, and two IgE
      binding sites on HRF have been mapped. HRF can form dimers, and a disulphide
      linked dimer is critical for activity. The current model for the activity of HRF
      in mast cell activation involves cross-linking of receptor-bound IgE by dimeric
      HRF, mediated by HRF/Fab interactions. HRF crystal and solution structures have
      provided little insight into either the formation of disulphide-linked HRF dimers
      or the ability of HRF to activate mast cells. We report the first crystal
      structure of murine HRF (mHRF) to 4.0A resolution, revealing a conserved fold. We
      also solved the structure of human HRF (hHRF) in two new crystal forms, one at
      the highest resolution (1.4A) yet reported. The high resolution hHRF structure
      reveals a disulphide-linked dimer, in which the two molecules are closely
      associated, and provides a model for the role of both human and murine HRF in
      mast cell activation.

PMID- 29216545
TI  - Occurrence of selected halogenated flame retardants in Belgian foodstuff.
AB  - This paper reports on the occurrence of halogenated flame retardants (HFRs),
      namely PBDEs, HBCDs, TBBPA, brominated phenols (BrPhs), dechlorane plus (DP) and
      emerging FRs in a variety of Belgian foodstuffs. A total of 183 composite food
      samples were analyzed by GC-MS and LC-MS/MS techniques for the presence of HFRs.
      The analyses revealed that 72% of the samples was contaminated with HFRs to some
      extent. The highest number of contaminated samples was observed within the group
      'Potatoes and derived products', 'Fish and fish products' and 'Meat and meat
      products', while the least contaminated group was 'Food for infants and small
      children'. The total HFR content ranged from <LOQ to 35.4 ng/g ww with an average
      content of 1.2 ng/g ww and median of 0.25 ng/g ww. The samples with the highest
      total HFR levels were canned king crab, fresh mackerel, Emmental cheese, fresh
      eel and plaice. The most frequently detected HFRs were PBDEs and BrPhs being
      present in almost all food groups, and among the individual HFRs, the most
      frequently found compounds were BDE-47 (53%), BDE-209 (46%) and 246-TBP (40%).
      TBBPA, DPs, TBPH and gamma-HBCD occurred with a frequency of less than 5%. TBBPS,
      26-DBP, HBB, TBB and BTBPE were not detected in any of the analyzed food samples.

PMID- 29216546
TI  - Adsorption and degradation of sulfadiazine and sulfamethoxazole in an
      agricultural soil system under an anaerobic condition: Kinetics and environmental
      risks.
AB  - Sulfonamides, one of the commonest antibiotics, were widely used on humans and
      livestock to control pathema and bacterial infections resulting in further
      environmental risks. The present study evaluated the adsorption and degradation
      of sulfadiazine (SDZ) and sulfamethoxazole (SMX) in an agricultural soil system
      under an anaerobic condition. Low sorption coefficients (Kd, 1.22 L kg-1 for SDZ
      and 1.23 L kg-1 for SMX) obtained from Freundlich isotherms experiment indicated
      that poor sorption of both antibiotics may pose a high risk to environment due to
      their high mobility and possibility of entering surface and ground water.
      Degradation occurred at a lower rate under the anaerobic environment, where both
      two antibiotics had higher persistence in sterile and non-sterile soils with
      degradation ratio <75% and DT50 > 20 d. Additionally, the addition of manure
      slightly increased degradation rates of SDZ and SMX, but there were no
      significant differences between single and repeated manure application at a later
      stage (p > 0.05), which suggested that the degradation was affected by both
      biotic and abiotic factors. Degradation rates would be slower at a higher
      concentration, indicating that degradation kinetics of SDZ and SMX were dependent
      on initial concentrations. During the degradation period, the antibiotics removal
      may change temperature, pH, sulfate and nitrate in soil, which suggested that the
      variation of antibiotics concentrations was related to the changes of soil
      physicochemical properties. An equation was proposed to elucidate the link
      between adsorption and degradation under different conditions, and to predict
      potential environmental risks of antibiotics.

PMID- 29216547
TI  - Seasonal variations of C1-C4 alkyl nitrates at a coastal site in Hong Kong:
      Influence of photochemical formation and oceanic emissions.
AB  - Five C1-C4 alkyl nitrates (RONO2) were measured at a coastal site in Hong Kong in
      four selected months of 2011 and 2012. The total mixing ratios of C1-C4 RONO2
      (Sigma5RONO2) ranged from 15.4 to 143.7 pptv with an average of 65.9 +/- 33.0
      pptv. C3-C4 RONO2 (2-butyl nitrate and 2-propyl nitrate) were the most abundant
      RONO2 during the entire sampling period. The mixing ratios of C3-C4 RONO2 were
      higher in winter than those in summer, while the ones of methyl nitrate (MeONO2)
      were higher in summer than those in winter. Source analysis suggests that C2-C4
      RONO2 were mainly derived from photochemical formation along with biomass burning
      (58.3-71.6%), while ocean was a major contributor to MeONO2 (53.8%) during the
      whole sampling period. The photochemical evolution of C2-C4 RONO2 was
      investigated, and found to be dominantly produced by the parent hydrocarbon
      oxidation. The notable enrichment of MeONO2 over C3-C4 RONO2 was observed in a
      summer episode when the air masses originating from the South China Sea (SCS) and
      MeONO2 was dominantly derived from oceanic emissions. In order to improve the
      accuracy of ozone (O3) prediction in coastal environment, the relative
      contribution of RONO2 from oceanic emissions versus photochemical formation and
      their coupling effects on O3 production should be taken into account in future
      studies.

PMID- 29216548
TI  - Temporal variability in Cu speciation, phytotoxicity, and soil microbial activity
      of Cu-polluted soils as affected by elevated temperature.
AB  - Global warming has obtained increasing attentions due to its multiple impacts on
      agro-ecosystem. However, limited efforts had been devoted to reveal the temporal
      variability of metal speciation and phytotoxicity of heavy metal-polluted soils
      affected by elevated temperature under the global warming scenario. In this
      study, effects of elevated temperature (15  degrees C, 25  degrees C, and 35 
      degrees C) on the physicochemical properties, microbial metabolic activities, and
      phytotoxicity of three Cu-polluted soils were investigated by a laboratory
      incubation study. Soil physicochemical properties were observed to be
      significantly altered by elevated temperature with the degree of temperature
      effect varying in soil types and incubation time. The Biolog and enzymatic tests
      demonstrated that soil microbial activities were mainly controlled and decreased
      with increasing incubation temperature. Moreover, plant assays confirmed that the
      phytotoxicity and Cu uptake by wheat roots were highly dependent on soil types
      but less affected by incubation temperature. Overall, the findings in this study
      have highlighted the importance of soil types to better understand the
      temperature-dependent alternation of soil properties, Cu speciation and
      bioavailability, as well as phytotoxicity of Cu-polluted soils under global
      warming scenario. The present study also suggests the necessary of investigating
      effects of soil types on the transport and accumulation of toxic elements in soil
      crop systems under global warming scenario.

PMID- 29216549
TI  - Kinetic research on dechlorinating dichlorobenzene in aqueous system by nano
      scale nickel/iron loaded with CMC/NFC hydrogel.
AB  - In this study, we reported on the nano-scale nickel/iron particles loaded in
      carboxymethyl/nanofibrillated cellulose (CMC/NFC) hydrogel for the dechlorination
      of o-dichlorobenzene (DCB) in aqueous solution. The biodegradable hydrogel may
      provide an ideal supporting material for fastening the bimetallic nano-scale
      particles, which was examined and characterized by TEM, SEM-EDX, FT-IR and BET.
      The performance of the selected bimetallic particles was evaluated by conducting
      the dechlorination of DCB in the solution under different reaction conditions
      (e.g., pH, dosage of nickel/iron nanoparticles and temperature). The results
      showed that about 70% of DCB could be dechlorinated at 20  degrees C in 8 h,
      which indicated that the immobilized reactive material had a high reduction
      activity when Ni/Fe loading dosage in the hydrogel (18 wt%) was considered.
      Moreover, the reduction behavior agreed to the pseudo-first order reaction, in
      which the dechlorination rate was irrelative to the pH aqueous solution. A
      kinetic model for predicting the concentration of DCB during the reduction
      reaction was established based on the experimental data.

PMID- 29216550
TI  - Response surface methodology optimization for sorption of malachite green dye on
      sugarcane bagasse biochar and evaluating the residual dye for phyto and
      cytogenotoxicity.
AB  - In the present study, sorption and detoxification of malachite green (MG) dye was
      executed using biochar resulting after pyrolysis of agro-industrial waste at 400,
      600 and 800  degrees C. Maximum sorption of MG dye (3000 mg/L) was observed on
      the sugarcane bagasse biochar (SCB) prepared at 800  degrees C. The interactive
      effects of different factors like dye concentration, time, pH and temperature on
      sorption of MG dye were investigated using response surface methodology (RSM).
      Optimum MG dye concentration, contact time, temperature and pH predicted through
      Box-Behnken based RSM model were 3000 mg/L MG dye, 51.89 min, 60  degrees C and
      7.5, respectively. ANOVA analysis displayed the non-significant lack of fit value
      (0.4566), whereas, the predicted correlation coefficient values (R2 0.8494) were
      reasonably in agreement with the adjusted value (R2 0.9363) demonstrating highly
      significant model for MG dye sorption. The applicability of this model was also
      checked through F- test (30.39) with lower probability (0.0001) value.
      Furthermore, the characterization of SCB was performed using fourier transform
      infra-red spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron
      microscope (SEM), Brunauer-Emmett-Teller surfaces (BET), total organic carbon
      (TOC) and atomic absorption spectroscopy (AAS). Phyto-toxicity and
      cytogenotoxicity studies showed successful removal of MG dye using SCB. In
      addition, the batch sorption studies for reutilization of SCB revealed that the
      SCB was effective in removal of MG for five repeated cycles. This technology
      would be effective for treating the toxic textile effluent released from the
      textile industries.

PMID- 29216551
TI  - Inhalation dose due to Rn-222, Rn-220 and their progeny in indoor environments.
AB  - Radon (Rn-222), thoron (Rn-220) and its progeny are the natural radioactive gases
      emitted everywhere in different concentration. These carcinogenic substances were
      known to be responsible for lung cancer. Human exposure of these gases in an
      indoor environment was principally dependent on the house types like concrete,
      slate, mud-tin etc. Rate of exposure is also influenced by unplanned construction
      and associated poor ventilation.The study of inhalation dose with house type and
      the associated indoor environment were important to study the exposure due to
      natural ionising radiation. In this study, we report the results from passive
      measurement of indoor radon, thoron and their progeny concentrations in Bilaspur
      district of Himachal Pradesh, India. The measurement was performed at selected 95
      dwellings, based on outdoor ambient gamma level and type of houses. Highest
      inhalation dose due to indoor radon, thoron and their progeny were found in mud
      houses in comparison to other concrete, slate and tin type of houses. The average
      annual inhalation dose thus found due to exposure to radon and thoron varies from
      0.1 to 0.5mSv/y in the concrete, 0.3-0.6 in mud and slate type of houses whereas
      0.1-0.4 in mud-tin type. The estimated average value of radon, thoron and their
      progeny concentrations were used to estimate total annual inhalation dose.

PMID- 29216552
TI  - Geographic and host size variations as indicators of Anisakis pegreffii infection
      in European pilchard (Sardina pilchardus) from the Mediterranean Sea: Food safety
      implications.
AB  - European pilchards are traditionally eaten marinated or salted in the
      Mediterranean countries often without thermal processing or gutting due to small
      size. Since ingestion of live third stage Anisakis larvae represents a causing
      agent in the onset of anisakiasis, the aim of our study was to assess prevalence
      and intensity of Anisakis infection in European pilchards originating from
      different Mediterranean regions in a three-year sampling period (2013-2015). A
      total of 1564 specimens of European pilchard collected from two geographically
      distinct sampling regions (western Mediterranean and Adriatic Sea) were examined
      using the UV-Press method, which utilises the fluorescence of frozen anisakids in
      flattened and subsequently frozen fillets and viscera. A subsample of 67 isolated
      larvae was identified as A. pegreffii by diagnostic allozyme markers and sequence
      analyses of the mtDNA cox2 locus. The overall prevalence in pilchards was 12.2%
      (range 0-44.9% for different sampling points) and mean intensity 1.8. More
      importantly, we have observed an overall larval prevalence of 1.5% in fillets.
      The highest prevalence (44.9%) was recorded in pilchards caught in western parts
      of the Mediterranean. As fish host size was a significant predictor of parasite
      abundance, it should be highlighted that these pilchards were also the largest
      (mean total length 173.2mm); on average >2cm larger than the rest of the samples.
      Other isolated nematode species included Hysterothylacium sp. in viscera, showing
      almost a double of A. pegreffii prevalence, 20.1%. In summary, our study
      demonstrates that the presence of A. pegreffii in European pilchards from the
      Mediterranean Sea is highly influenced by both geographic and host size
      variation. This implies that, before future risk management measures are
      developed, these variables should be assessed in order to minimize public health
      concerns.

PMID- 29216553
TI  - Mathematical quantification of the induced stress resistance of microbial
      populations during non-isothermal stresses.
AB  - This contribution presents a mathematical model to describe non-isothermal
      microbial inactivation processes taking into account the acclimation of the
      microbial cell to thermal stress. The model extends the log-linear inactivation
      model including a variable and model parameters quantifying the induced thermal
      resistance. The model has been tested on cells of Escherichia coli against two
      families of non-isothermal profiles with different constant heating rates. One of
      the families was composed of monophasic profiles, consisting of a non-isothermal
      heating stage from 35 to 70 degrees C; the other family was composed of biphasic
      profiles, consisting of a non-isothermal heating stage followed by a holding
      period at constant temperature of 57.5 degrees C. Lower heating rates resulted in
      a higher thermal resistance of the bacterial population. This was reflected in a
      higher D-value. The parameter estimation was performed in two steps. Firstly, the
      D and z-values were estimated from the isothermal experiments. Next, the
      parameters describing the acclimation were estimated using one of the biphasic
      profiles. This set of parameters was able to describe the remaining experimental
      data. Finally, a methodology for the construction of diagrams illustrating the
      magnitude of the induced thermal resistance is presented. The methodology has
      been illustrated by building it for a biphasic temperature profile with a linear
      heating phase and a holding phase. This diagram provides a visualization of how
      the shape of the temperature profile (heating rate and holding temperature)
      affects the acclimation of the cell to the thermal stress. This diagram can be
      used for the design of inactivation treatments by industry taking into account
      the acclimation of the cell to the thermal stress.

PMID- 29216554
TI  - Active nanocomposite films based on soy proteins-montmorillonite- clove essential
      oil for the preservation of refrigerated bluefin tuna (Thunnus thynnus) fillets.
AB  - This manuscript evaluates the potential application of active nanocomposite films
      based on soy protein isolate (SPI)-montmorillonite (MMT)-clove essential oil
      (CEO) to the preservation of muscle fillets of bluefin tuna (Thunnus thynnus)
      during refrigerated storage, and furthermore analyzes whether the clay diffuses
      from the package to food. SPI films with: CEO (SPI-CEO), MMT (SPI-MMT), or both
      CEO and MMT (SPI-MMT-CEO), were prepared and used to cover tuna fillets during
      17days of storage at 2 degrees C. Polyethylene films were also used as control.
      Protein films nanoreinforced with 10g MMT/100g SPI and activated with CEO were
      able to decrease microbial growth (evaluated by TVBN and microorganism counts)
      and lipid autooxidation (evaluated according to the TBA index, FTIR and color
      parameters) of tuna fillets during the storage period studied. The presence of
      clay seemed to favor the release of the active principles of clove oil by
      prolonging its antimicrobial (especially effective to inhibit Pseudomonas spp.)
      and antioxidant activity over time without observing the diffusion of the clay's
      own metals (Si and Al) from the nanocomposite materials to the muscle of fish.
      These results are encouraging for the use of nanocomposite films in food
      packaging.

PMID- 29216555
TI  - Investigation on chlorine-based sanitization under stabilized conditions in the
      presence of organic load.
AB  - Chlorine, the most commonly used sanitizer for fresh produce washing, has
      constantly shown inferior sanitizing efficacy in the presence of organic load.
      Conventionally this is attributed indirectly to the rapid chlorine depletion by
      organics leading to fluctuating free chlorine (FC) contents. However, little is
      known on whether organic load affects the sanitization process directly at well
      maintained FC levels. Hereby, a sustained chlorine decay approach was employed to
      study the inactivation of Escherichia coli O157:H7 under stabilized washing
      conditions. Chlorine solution was first incubated with organic load for up to 4h,
      modeling the chlorination in produce washing lines. The FC level was then
      stabilized at five targeted values for sanitization study. Our study showed
      decreased sanitizing efficacy as the organic load increased. At 5s residence time
      and pH6.5, a minimum of 0.5 and 7.5mg/L FC were needed to achieve a 5 log
      reduction at 0 and 900mg/L chemical oxygen demand (COD), respectively. The
      decrease was more pronounced at lower FC, higher COD, higher pH, and shorter
      residence time values. The organics-associated interference with FC measurement
      and disruption of chlorine/bacteria interaction, together with the chlorine
      demand of concentrated inoculum per se, collectively resulted in inadequate
      sanitization. Finally, our results were compared with existing studies conducted
      under dynamic conditions in the context of different experimental settings. This
      study provided a feasible method for studying the bacteria/sanitizer interaction
      while ruling out the confounding effect from fluctuating FC levels, and it
      indicated the direct, negative impact of organic load.

PMID- 29216556
TI  - Influence of water activity and temperature on growth and fumonisin production by
      Fusarium proliferatum strains on irradiated wheat grains.
AB  - Wheat is the most important cereal consumed by the Argentine population. In
      previous studies performed in durum and common wheat grains in this country it
      has been observed fumonisin contamination as well as high incidence of Fusarium
      proliferatum. Fumonisins are toxic fungal metabolites, and consumption of
      fumonisin-contaminated maize has been epidemiologically associated with
      oesophageal cancer and neural tube defects in some human populations. Using
      irradiated wheat-grains, the effects of abiotic factors, temperature (15, 25, and
      30 degrees C) and water activity (aW; 0.995, 0.98, 0.96, 0.94, 0.92, and 0.88),
      on mycelial growth and fumonisin biosynthesis were compared for three F.
      proliferatum strains isolated from wheat grains in Argentina. Although all
      isolates showed similar profiles of growth, the fumonisin production profiles
      were slightly different. Maximum growth rates were obtained at the highest aW
      (0.995) and 25 degrees C, with growth decreasing as the aW of the medium was
      reduced. Maximum amounts of total fumonisins (FB1, FB2 and FB3) were produced at
      0.995 aW and 15 degrees C for 2 strains, and at 25 degrees C and 0.995 aW for the
      third one. Fumonisins concentrations varied considerably depending on the aW and
      temperature interactions assayed. Studied strains showed different fumonisin
      production profiles. Two-dimensional profiles of aW by temperature interactions
      were developed from these data to identify areas where conditions indicate a
      significant risk of fumonisins accumulation on wheat. As a result, temperature
      and aW conditions that resulted in fumonisins production are those found during
      wheat grain development (especially milk and dough stages) in the field. This is
      the first study made using irradiated wheat grains and provides useful baseline
      data on conditions representing a low or a high risk for fumonisins contamination
      of wheat grains which is of concern because this cereal is destined mainly for
      human consumption.

PMID- 29216557
TI  - Subcortical volumetric differences between clinical stages of young people with
      affective and psychotic disorders.
AB  - The aim of this study was to investigate differences in subcortical and
      hippocampal volumes between healthy controls, young people at an early stage of
      affective and psychotic disorders and those in more advanced stages, to identify
      markers associated with functional outcomes and illness severity. Young people
      presenting to youth mental health services with admixtures of depressive, manic
      and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25
      were recruited. Participants underwent magnetic resonance imaging, clinical
      assessments and were rated as to their current clinical stage. Eighty-four
      patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were
      classified as having discrete and persistent disorders (Stage 2+). Automated
      segmentation was performed using NeuroQuant(r) to determine volumes of
      subcortical and hippocampus structures which were compared between groups and
      correlated with clinical and functional outcomes. Compared to healthy controls,
      Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas
      Stage 1b patients showed significantly reduced left caudate volumes compared to
      healthy controls. Smaller left caudate volume correlated with greater
      psychological distress and impaired functioning. This study shows a clinical
      application for an automated program to identify and track subcortical changes
      evident in young people with emerging psychopathology.

PMID- 29216558
TI  - Maternal support following childhood sexual abuse: Relationships to child
      reported.
AB  - Maternal support has been conceptualized as a key factor in predicting children's
      functioning following sexual abuse; however, empirical evidence for this
      assumption is rather limited. Prior studies may have failed to find a
      relationship between maternal support and children's outcomes due to the
      methodological weaknesses of the prior literature such as the use of maternal
      support measures without adequately reported psychometric properties. Moreover,
      relatively few studies have investigated whether maternal support corresponds
      with children's own self-reported symptoms. The aim of the present study was to
      utilize the only published measure of maternal support with sufficient
      psychometrics, the Maternal Self-Report Support Questionnaire (MSSQ; Smith et
      al., 2010), to determine if levels of pre-treatment support are associated with
      children's self-reported trauma-related symptoms among 165 treatment-seeking
      children (M=10.85, SD=3.09) and their non-offending mothers. Levels of maternal
      emotional support corresponded with few of children's outcomes, and when
      relationships were observed, emotional support was related to higher levels of
      symptoms. Maternal levels of blame and doubt were only associated with
      dissociative symptoms. Maternal support therefore appears to be an ineffective
      predictor of children's post-disclosure trajectories and raises the possibility
      that maternal support is linked with poorer functioning.

PMID- 29216559
TI  - Pregnancy outcomes and ethanol cook stove intervention: A randomized-controlled
      trial in Ibadan, Nigeria.
AB  - BACKGROUND: Household air pollution (HAP) exposure has been linked to adverse
      pregnancy outcomes. OBJECTIVES: A randomized controlled trial was undertaken in
      Ibadan, Nigeria to determine the impact of cooking with ethanol on pregnancy
      outcomes. METHODS: Three-hundred-twenty-four pregnant women were randomized to
      either the control (continued cooking using kerosene/firewood stove, n=162) or
      intervention group (received ethanol stove, n=162). Primary outcome variables
      were birthweight, preterm delivery, intrauterine growth restriction (IUGR), and
      occurrence of miscarriage/stillbirth. RESULTS: Mean birthweights for ethanol and
      controls were 3076 and 2988g, respectively; the difference, 88g, (95% confidence
      interval: -18g to 194g), was not statistically significant (p=0.10). After
      adjusting for covariates, the difference reached significance (p=0.020). Rates of
      preterm delivery were 6.7% (ethanol) and 11.0% (control), (p=0.22). Number of
      miscarriages was 1(ethanol) vs. 4 (control) and stillbirths was 3 (ethanol) vs. 7
      (control) (both non-significant). Average gestational age at delivery was
      significantly (p=0.015) higher in ethanol-users (39.2weeks) compared to controls
      (38.2weeks). Perinatal mortality (stillbirths and neonatal deaths) was twice as
      high in controls compared to ethanol-users (7.9% vs. 3.9%; p=0.045, after
      adjustment for covariates). We did not detect significant differences in exposure
      levels between the two treatment arms, perhaps due to large seasonal effects and
      high ambient air pollution levels. CONCLUSIONS: Transition from traditional
      biomass/kerosene fuel to ethanol reduced adverse pregnancy outcomes. However, the
      difference in birthweight was statistically significant only after covariate
      adjustment and the other significant differences were in tertiary endpoints. Our
      results are suggestive of a beneficial effect of ethanol use. Larger trials are
      required to validate these findings.

PMID- 29216560
TI  - Identification of an oxime-containing C-glucosylarene as a potential inhibitor of
      sodium-dependent glucose co-transporter 2.
AB  - Treatment of hyperglycemia with drugs that block renal glucose reabsorption via
      inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel
      approach to diabetes management. In this study, twenty-seven aryl C-glycosides
      bearing a C=N/C-N linkage at the glucosyl C6 position were designed, synthesized
      and evaluated for their inhibitory activity against human SGLT2 (hSGLT2).
      Compounds with good hSGLT2 inhibition were further investigated to determine
      their selectivity over hSGLT1. Of these, five representative aryl C-glycosides
      were chosen for pharmacokinetic analysis. Oxime 2a was determined to have the
      most promising pharmacokinetic properties and was selected for in vivo glucosuria
      and plasma glucose level studies, which found it to exhibit comparable efficacy
      to dapagliflozin (1). Furthermore, 2a was not found to exhibit either significant
      cytotoxicity (CC50 > 50 MUM) or human ether-a-go-go related gene (hERG)
      inhibition (2% inhibition at 10 MUM). Taken together, these efforts culminated in
      the discovery of oxime 2a as a potential SGLT2 inhibitor.

PMID- 29216561
TI  - Design, synthesis and evaluation of an anthraquinone derivative conjugated to
      myelin basic protein immunodominant (MBP85-99) epitope: Towards selective
      immunosuppression.
AB  - Anthraquinone type compounds, especially di-substituted amino alkylamino
      anthraquinones have been widely studied as immunosuppressants. The anthraquinone
      ring is part of mitoxandrone that has been used for the treatment of multiple
      sclerosis (MS) and several types of tumors. A desired approach for the treatment
      of MS would be the immunosuppression and elimination of specific T cells that are
      responsible for the induction of the disease. Herein, the development of a
      peptide compound bearing an anthraquinone derivative with the potential to
      specifically destroy the encephalitogenic T cells responsible for the onset of MS
      is described. The compound consists of the myelin basic protein (MBP) 85-99
      immunodominant epitope (MBP85-99) coupled to an anthraquinone type molecule (AQ)
      via a disulfide (S-S) and 6 amino hexanoic acid (Ahx) residues (AQ-S-S
      (Ahx)6MBP85-99). AQ-S-S-(Ahx)6MBP85-99 could bind to HLA II DRB1*-1501 antigen
      with reasonable affinity (IC50 of 56 nM) The compound was localized to the
      nucleus of Jurkat cells (an immortalized line of human T lymphocytes) 10 min
      after its addition to the medium and resulted in lowered Bcl-2 levels
      (apoptosis). Entrance of the compound was abolished when cells were pre-treated
      with cisplatin, an inhibitor of thioredoxin reductase. Accordingly, levels of
      free thiols were elevated in the culture supernatants of Jurkat cells exposed to
      N-succinimidyl 3-(2-pyridyldithio) propionate coupled to (Ahx)6MBP85-99 via a
      disulphide (SPDP-S-S-(Ahx)6MBP85-99) but returned to normal after exposure to
      cisplatin. These results raise the possibility of AQ-S-S-(Ahx)6MBP85-99 being
      used as an eliminator of encephalitogenic T cells via implication of the
      thioredoxin system for the generation of the toxic, thiol-containing moiety (AQ
      SH). Future experiments would ideally determine whether SPDP-S-S-(Ahx)6MBP85-99
      could incorporate into HLA II DRB1*-1501 tetramers and neutralize
      encephalitogenic T cell lines sensitized to MBP85-99.

PMID- 29216562
TI  - Substituted carbamothioic amine-1-carbothioic thioanhydrides as novel
      trichomonicidal fungicides: Design, synthesis, and biology.
AB  - Sexually transmitted diseases like trichomoniasis along with opportunistic fungal
      infections like candidiasis are major global health burden in female reproductive
      health. In this context a novel non-nitroimidazole class of substituted
      carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized,
      evaluated for trichomonacidal and fungicidal activities, and was found to be more
      active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal
      in the MIC ranges of 4.77-294.1 MUM and 32.46-735.20 MUM against MTZ-susceptible
      and -resistant strains, respectively. Further, compounds inhibited the growth of
      at least two out of ten fungal strains tested at MIC of 7.50-240.38 MUM. The most
      active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ
      against the two Trichomonas strains tested. Compound 20 also significantly
      inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found
      to be more active than the MTZ in vivo. Further, a docking analysis carried out
      with cysteine proteases supported their thiol inhibiting ability and preliminary
      pharmacokinetic study has shown good distribution and systemic clearance.

PMID- 29216563
TI  - Synthesis and antimicrobial activity of amino acid and peptide derivatives of
      mycophenolic acid.
AB  - The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives
      was obtained as potential antibacterial agents. Coupling of MPA with respective
      amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA.
      Amino acid analogs were received both as methyl esters and also with the free
      carboxylic group. The biological activity of the products was tested on five
      references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL),
      Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus
      aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide
      derivatives proved to be the most versatile ones, their MIC values relative to
      most strains was lower than MPA alone. It has been noted that the activity of
      amino acid derivatives depends on the configuration at the chiral center in the
      amino acid unit and methyl esters indicated better antimicrobial activity than
      analogs with free carboxylic group.

PMID- 29216564
TI  - p27kip1 as a key regulator of endometriosis.
AB  - p27kip1 as a key regulator of endometriosis Goncalves GA p27kip1 is a cyclin
      dependent kinase (CDK) inhibitor whose specific late G1 destruction allows
      progression of the cell across the G1/S boundary. There is a direct relationship
      between low level of p27 and rapid proliferation occurring in several benign
      states and in many malignances. In the glandular cells of the normal endometrium,
      the level of p27kip1 is exceedingly low during the proliferative phase, whereas
      it is markedly increased during the secretory phase. The expression of p27kip1 in
      endometriosis is very low but has been found to increase following treatment with
      progesterone. However, estrogen exposure is considered as a major risk factor in
      developing endometrial cancer. Endometriosis endometrial cells cultures have also
      lower levels of p27kip1 compared to heath endometrial cells cultures and restore
      the cell cycle balance when transduced with an adenoviral vector carring the
      p27kip1 coding gene (Adp27EGFP). More uniform and rigorous studies are required
      to confirm these and additional markers utility in a diagnostic and possible
      treatment panel. As a major clinical priority is to determine which lesions can
      be treated medically and which require surgical intervention, focusing future
      studies on markers that distinguish response to hormone therapy or are involved
      in hormone regulation, will be important future considerations. The goal of this
      highlight review is to provide a broad overview of the advancements in studies
      about endometriosis mainly correlating the cytokine p27kip1 expression with the
      diagnostic and disease treatment.

PMID- 29216565
TI  - Incidence, prevalence, mortality, disability-adjusted life years and risk factors
      of cancer in Australia and comparison with OECD countries, 1990-2015: findings
      from the Global Burden of Disease Study 2015.
AB  - BACKGROUND: Comparative evidence on the burden, trend, and risk factors of cancer
      is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to
      assess cancer burden - incidence, prevalence, mortality, disability-adjusted life
      years (DALYs) - and attributable risk factors for Australia between 1990 and
      2015, and to compare them with those of 34 members of the Organisation for
      Economic Co-operation and Development (OECD). METHODS: The general GBD cancer
      estimation methods were used with data input from vital registration systems and
      cancer registries. A comparative risk assessment approach was used to estimate
      the population-attributable fractions due to risk factors. RESULTS: In 2015 there
      were 198,880 (95% uncertainty interval [UI]: 183,908-217,365) estimated incident
      cancer cases and 47,562 (95% UI: 46,061-49,004) cancer deaths in Australia.
      Twenty-nine percent (95% UI: 28.2-29.8) of total deaths and 17.0% (95% UI: 15.0
      19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the
      trachea, bronchus and lung, colon and rectum, and prostate were the most common
      causes of cancer deaths. Thirty-six percent (95% UI: 33.1-37.9) of all cancer
      deaths were attributable to behavioral risks. The age-standardized cancer
      incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized
      cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34
      other OECD countries Australia ranked first (highest) and 24th based on ASIR and
      ASDR, respectively. CONCLUSION: The incidence of cancer has increased over 25
      years, and behavioral risks are responsible for a large proportion of cancer
      deaths. Scaling up of prevention (using strategies targeting cancer risk
      factors), early detection, and treatment of cancer is required to effectively
      address this growing health challenge.

PMID- 29216566
TI  - New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base
      with a fluorescent chemosensor properties: Synthesis, spectroscopic
      characterization, X-ray structure determination, in vitro anticancer activity on
      various human carcinoma cell lines and computational studies.
AB  - A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II)
      complexes; ([Pd(L)2] and [Pt(L)2]), were synthesized and characterized using
      spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and
      conductivity measurements. A single crystal X-ray analysis for only L was done.
      The crystals of L have monoclinic crystal system and P21/c space group. To gain
      insight into the structure of L and its complexes, we used density functional
      theory (DFT) method to optimize the molecules. The photophysical properties
      changes were observed after deprotonation of L with CN- via intermolecular charge
      transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric
      cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N),
      it showed fast color change from yellow to deep red in the visible region, and
      yellow fluorescence after CN- addition to the imine bond, in DMSO. The reaction
      mechanisms of L with CN-, F- and AcO- ions were evaluated using 1H NMR shifts.
      The results showed that, the reaction of L with CN- ion was due to the
      deprotonation and addition mechanisms at the same time. The anti-cancer activity
      of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay
      on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human
      colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer
      effects of L and its complexes, on human cells, were determined by comparing the
      half maximal inhibitory concentration (IC50) values. The activity results showed
      that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II)
      complex against the tested human breast adenocarcinoma (MCF-7), human prostate
      adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines.

PMID- 29216567
TI  - Biocompatible nanocomposite of TiO2 incorporated bi-polymer for articular
      cartilage tissue regeneration: A facile material.
AB  - The development and design of polymeric hydrogels for articular cartilage tissue
      engineering have been a vital biomedical research for recent days.
      Organic/inorganic combined hydrogels with improved surface activity have shown
      potential for the repair and regeneration of hard tissues, but have not been
      broadly studied for articular cartilage tissue engineering applications. In this
      work, bi-polymeric hydrogel composite was designed with the incorporation some
      quantities of stick-like TiO2 nanostructures for favorable surface behavior and
      enhancement of osteoblast adhesions. The microscopic investigations clearly
      exhibited that the stick-like TiO2 nanostructured materials are highly inserted
      into the PVA/PVP bi-polymeric matrix, due to the long-chain PVA molecules are
      promoted to physical crosslinking density in hydrogel network. The results of
      improved surface topography of hydrogel matrixes show that more flatted cell
      morphologies and enhanced osteoblast attachment on the synthesized
      nanocomposites. The crystalline bone and stick-like TiO2 nanocomposites
      significantly improved the bioactivity via lamellipodia and filopodia extension
      of osteoblast cells, due to its excellent intercellular connection and regulated
      cell responses. Consequently, these hydrogel has been enhanced the antibacterial
      activity against Staphylococcus aureus and Escherichia coli bacterial pathogens.
      Hence it is concluded that these hydrogel nanocomposite with improved morphology,
      osteoblast behavior and bactericidal activity have highly potential candidates
      for articular cartilage tissue regeneration applications.

PMID- 29216568
TI  - Nigella sativa oil modulates the therapeutic efficacy of mesenchymal stem cells
      against liver injury in irradiated rats.
AB  - Stem cell transplantation is a novel strategy for regenerative medicine in liver
      disease. This study was conducted to explore the modulatory effect of Nigella
      sativa oil (NSO) on the therapeutic potential of mesenchymal stem cells (MSCs)
      against irradiation-induced liver damage in rats. Liver damage was induced by a
      total body exposure to a single dose of 7Gy. NSO (2mg/kg/day) was then given
      orally for 4 consecutive weeks starting 24h after irradiation with or without a
      single intravenous MSCs administration, then rats were sacrificed four weeks
      after exposure to gamma radiation. Data revealed that irradiation elevated
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in
      serum, increased hepatic malondialdehyde (MDA) content and reduced hepatic
      superoxide dismutase (SOD) activity. Furthermore, it caused elevation in pro
      inflammatory mediators such as interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) associated with reduction in anti-inflammatory cytokine
      interleukin-10 (IL-10) and it increased fibrogenic marker transforming growth
      factor-beta (TGF-beta) in liver tissues. It was observed that combined NSO/MSCs
      therapy provided more beneficial tissue repair comparable to MSCs alone as
      demonstrated by modulating the tested parameters. Finally, these results were
      confirmed by histopathological examination. In conclusion, dual therapy with NSO
      and MSCs could serve as a promising approach for alleviating radiation-induced
      liver injury in patients with radiotherapy.

PMID- 29216569
TI  - A randomized, controlled pilot study of warm handoff versus fax referral for
      hospital-initiated smoking cessation among people living with HIV/AIDS.
AB  - INTRODUCTION: The prevalence of smoking among people living with HIV/AIDS (PLWHA)
      remains higher than the general population. Life expectancy among PLWHA has
      increased over the past decade, however, PLWHA who smoke will die younger than
      their non-smoking peers. The primary aim of this pilot study was to examine the
      effects of warm handoff versus fax referral to the quitline for smoking cessation
      among hospitalized smokers living with HIV/AIDS. METHODS: 25 smokers with a
      diagnosis of HIV/AIDS hospitalized at a Midwestern academic medical center in
      2012-2013 (19 male; mean age=47.7; 48% African-American) were identified,
      approached, and randomized to one of two treatment arms. At the bedside for
      patients in warm handoff, staff telephoned the quitline for on-the-spot
      enrollment and counseling. Participants randomized to fax were fax-referred to
      the quitline on the day of discharge. The quitline provided continued outpatient
      counseling to participants in both conditions. The main outcome was verified
      tobacco abstinence at 6-months post randomization. RESULTS: Enrollment and
      participation in quitline counseling was high among both warm handoff (100%) and
      fax-referred (71.4%) PLWHA participants. Nearly all completed follow up for
      outcome data collection at 6months. Verified abstinent rates were 45.5% in warm
      handoff versus 14.3% in fax referral at 6months (not significant). CONCLUSIONS:
      Hospitalized smokers living with HIV/AIDS were highly engaged in quitline
      services. Warm handoff seems a promising intervention for hospitalized PLWHA that
      requires further exploration. Clinical Trials Registration NCT01305928.

PMID- 29216570
TI  - The effects of alcohol hangover on future drinking behavior and the development
      of alcohol problems.
AB  - INTRODUCTION: Alcohol hangover experiences in young adulthood have been shown to
      predict more subsequent alcohol problems. Hangover susceptibility appears to be
      partially heritable and related to family history of alcohol use disorders.
      However, very little is known about the developmental course of these
      associations and whether they are accounted for by an individual's drinking
      history. The goal of this study is to investigate the prospective and unique
      relationships between family history of alcohol use disorders, severity of
      alcohol hangover experiences in adolescence, and later alcohol use and related
      problems measured over 13years. METHODS: Participants were first assessed on
      family history at age 12-14, prior to initiating drinking, and re-assessed
      annually on hangover severity, drinks per drinking day (DPDD), and alcohol
      related problems throughout the 13-year follow-up period (n=205; 59% male).
      RESULTS: In mixed effects negative binomial regression models, greater family
      history density scores predicted more future DPDD (Incidence Rate Ratio
      [IRR]=1.19, p=0.04), alcohol problems (IRR=1.64, p=0.05), and future hangover
      severity (IRR=1.24; p=0.01). In turn, greater hangover severity predicted more
      future DPDD (IRR=1.03; p=0.002) and alcohol problems (IRR=1.12, p<0.001), and
      hangover severity mediated the relationship between family history and alcohol
      use/problems. All models controlled for participant age, sex, and past drinking
      behavior (where relevant). CONCLUSIONS: These results advance the alcohol
      hangover experience during late adolescence as a clinically relevant and uniquely
      informative marker of future alcohol use and problems, above and beyond that of
      prior personal or familial drinking history.

PMID- 29216571
TI  - Negative affectivity as a mechanism underlying perceived distress tolerance and
      cannabis use problems, barriers to cessation, and self-efficacy for quitting
      among urban cannabis users.
AB  - Cannabis use rates continue to rise in the United States and currently cannabis
      is among the most widely used substances in the world. Cannabis use is associated
      with several mental health problems, low educational attainment, low income, and
      underemployment. The current study explored the tendency to experience negative
      affect (negative affectivity) as a factor accounting for the association between
      perceived distress tolerance and problems related to the use of cannabis.
      Participants included 203 urban adult daily cannabis users (29.2% female,
      M=37.7years, 63% African American). Results indicated that there was a
      significant indirect effect of distress tolerance via negative affectivity in
      terms of cannabis use problems (b=-0.58, 95%CI [-1.14, -0.21]), cannabis
      withdrawal (b=-0.65, 95%CI [-1.36, -0.21]), self-efficacy for quitting (b=-0.83,
      95%CI [-1.85, -0.22]), and perceived barriers for cannabis cessation (b=-0.71,
      95%CI [-1.51, -0.24]). The present data provide novel empirical evidence
      suggesting negative affectivity may help explain the relation between perceived
      distress tolerance and an array of clinically significant cannabis use processes.
      Intervention programming for daily cannabis users may benefit from targeting
      negative affectivity to facilitate change in cannabis use processes among users
      who tend to perceive that they are less capable of tolerating distress.

PMID- 29216572
TI  - Gene expression profiling of astaxanthin and fatty acid pathways in Haematococcus
      pluvialis in response to different LED lighting conditions.
AB  - Haematococcus pluvialis is a green microalga of major interest to industry based
      on its ability to produce large amounts of astaxanthin. Biosynthesis of
      astaxanthin and its mono- and di-esters was significantly stimulated under 150
      MUmol m-2 s-1 of white LED (W-150) compared with lower light intensities, but the
      highest astaxanthin amounts were produced under 70 MUmol m-2 s-1 of blue LED (B
      70). Transcripts of astaxanthin biosynthesis genes psy, crtO, and bkt2 were
      upregulated under W-150, while psy, lcy, crtO, and crtR-B were upregulated by B
      70. Total fatty acid content and biosynthesis genes fata and all dgat genes were
      induced under W-150, while C18:3n6 biosynthesis and dgat2a expression were
      specifically stimulated by B-70 which was correlated to astaxanthin ester
      biosynthesis. Nitrogen starvation, various LEDs and the identified upregulated
      genes may provide useful tools for future metabolic engineering to significantly
      increase free astaxanthin, its esters and fatty acid precursors in H. pluvialis.

PMID- 29216573
TI  - Nitrogen removal performance and microbial community changes in subsurface
      wastewater infiltration systems (SWISs) at low temperature with different
      bioaugmentation strategies.
AB  - Poor nitrogen removal efficiency (mainly nitrate, NO3--N) at low temperatures
      strongly limits application of subsurface wastewater infiltration systems
      (SWISs). Seven psychrophilic strains (heterotrophic nitrifying bacteria and
      aerobic denitrifying bacteria) were isolated and added to SWISs to investigate
      the effect of embedding and direct-dosing bioaugmentation strategies on sewage
      treatment performance at low temperature. Both bioaugmentation strategies
      improved ammonium (NH4+-N) removal efficiencies, and the embedding strategy also
      exhibited satisfactory NO3--N and total nitrogen (TN) removal efficiencies.
      Pyrosequencing results of the bacterial 16S rRNA gene indicated that the
      embedding strategy significantly decreased the indigenous soil microbial
      diversity (p < .05) and altered the bacterial community structure, significantly
      increasing the relative abundance of Clostridia, which have good nitrate-reducing
      activity.

PMID- 29216574
TI  - Methane production and characteristics of the microbial community in the co
      digestion of spent mushroom substrate with dairy manure.
AB  - Spent mushroom substrate (SMS) is a potential biomass material generated during
      mushroom cultivation. In this study, the methane yield and microbial community
      resulting from co-digestion of SMS and dairy manure (DM) at different mixing
      ratios (0:4, 1:1, 3:1, and 1:3), were evaluated. Co-digestion analysis showed
      that the methane yield from the mixtures was 6%-61% higher than the yield from
      SMS or DM alone, indicating a synergistic effect of co-digestion of SMS with DM.
      For the SMS of F.velutipes (SFv) and P.erygii var. tuoliensis (SPt), co-digestion
      of DM/SMS at a ratio of 1:1 was optimal, but for the SMS of P. eryngi (SPe), co
      digestion of DM/SMS at a ratio of 3:1 was ideal. The pH at all co-digestion
      ratios was in the range of 6.8-8.0, indicating that adding DM could increase the
      systemic buffering capacity. Methanosaetaceae was shown to be the predominant
      methanogens present during the co-digestion of DM/SMS.

PMID- 29216575
TI  - Tuning the Schottky rectification in graphene-hexagonal boron nitride-molybdenum
      disulfide heterostructure.
AB  - It was still a great challenge to design high performance of rectification
      characteristic for the rectifier diode. Lately, a new approach was proposed
      experimentally to tune the Schottky barrier height (SBH) by inserting an
      ultrathin insulated tunneling layer to form metal-insulator-semiconductor (MIS)
      heterostructures. However, the electronic properties touching off the high
      performance of these heterostructures and the possibility of designing more
      efficient applications for the rectifier diode were not presently clear. In this
      paper, the structural, electronic and interfacial properties of the novel MIS
      diode with the graphene/hexagonal boron nitride/monolayer molybdenum disulfide
      (GBM) heterostructure had been investigated by first-principle calculations. The
      calculated results showed that the intrinsic properties of graphene and MoS2 were
      preserved due to the weak van der Waals contact. The height of interfacial
      Schottky barrier can be tuned by the different thickness of hBN layers. In
      addition, the GBM Schottky diode showed more excellent rectification
      characteristic than that of GM Schottky diode due to the interfacial band bending
      caused by the epitaxial electric field. Based on the electronic band structure,
      we analyzed the relationship between the electronic structure and the nature of
      the Schottky rectifier, and revealed the potential of utilizing GBM Schottky
      diode for the higher rectification characteristic devices.

PMID- 29216576
TI  - Characterizing adsorption of associating surfactants on carbonates surfaces.
AB  - HYPOTHESIS: The adsorption of anionic surfactants onto positively charged
      carbonate minerals is typically high due to electrostatic interactions. By
      blending anionic surfactants with cationic or zwitterionic surfactants, which
      naturally form surfactant complexes, surfactant adsorption is expected to be
      influenced by a competition between surfactant complexes and surfactant-surface
      interactions. EXPERIMENTS: The adsorption behavior of surfactant blends known to
      form complexes was investigated. The surfactants probed include an anionic C15-18
      internal olefin sulfonate (IOS), a zwitterionic lauryl betaine (LB), and an
      anionic C13-alcohol polyethylene glycol ether carboxylic acid (L38). An
      analytical method based on high-performance liquid chromatography evaporative
      light scattering detector (HPLC-ELSD) was developed to measure three individual
      surfactant concentrations from a blended surfactant solution. The adsorption of
      the individual surfactants and surfactant blends were systematically investigated
      on different mineral surfaces using varying brine solutions. FINDINGS: LB
      adsorption on calcite surfaces was found to be significantly increased when
      blended with IOS or L38 since it forms surfactant complexes that partition to the
      surface. However, the total adsorption of the LB-IOS-L38 solution on dolomite
      decreased from 3.09 mg/m2 to 1.97 mg/m2 when blended together compared to summing
      the adsorption values of individual surfactants, which highlights the importance
      of mixed surfactant association.

PMID- 29216577
TI  - Performance enhancement of perovskite solar cells by employing TiO2 nanorod
      arrays decorated with CuInS2 quantum dots.
AB  - In this work, TiO2 nanorod arrays (TiO2-NAs) were modified by CuInS2 quantum dots
      (CuInS2 QDs) on the surface of the nanorods. The resultant TiO2-CuInS2 nanorod
      arrays (TiO2-CuInS2-NAs) were characterized by UV/Vis spectroscopy, transmission
      electronic microscopy (TEM), and X-ray diffraction (XRD). The TiO2-CuInS2-NAs
      were applied as scaffold for the preparation of organic-inorganic hybrid
      perovskite solar cells. In comparison with the solar cell devices based on TIO2
      NAs, a significant improvement in the power conversion efficiency had been
      achieved and the highest efficiency was obtained as 11.7% (under 100 mW/cm2)
      through the optimization of the growth time of QDs on nanorods. The improvement
      of the device performance could be attributed to the assistance of CuInS2 QDs in
      the light harvesting as well as the facilitation of the electron injection from
      the perovskite to the TiO2 scaffold.

PMID- 29216578
TI  - Preparation and characterization of xanthan gum-cl-poly(acrylic acid)/o-MWCNTs
      hydrogel nanocomposite as highly effective re-usable adsorbent for removal of
      methylene blue from aqueous solutions.
AB  - In this work, xanthan gum-cl-poly acrylic acid (XG-cl-pAA) hydrogel and xanthan
      gum-cl-poly acrylic acid/oxidized MWCNTs (XG-cl-pAA/o-MWCNTs) hydrogel
      nanocomposite was successfully surface modify by microwave assisted
      copolymerization, in which N, N'-methylenebisacrylamide (MBA) was used as a cross
      linking agent. A copolymerization of acrylic acid (AA) onto xanthan gum (XG)
      initiated by microwave radiation method. Different weight percentages of oxidized
      MWCNTs were incorporated into the hydrogel matrix during the grafting reaction.
      An optimum hydrogel based on maximum swelling capacity further incorporated with
      oxidized MWCNTs to form XG-cl-pAA/o-MWCNTs. The structure, thermal stability,
      wettability and morphology of XG-cl-PAA and XG-cl-PAA/o-MWCNTs were characterized
      by fourier transform infrared (FTIR), Raman, X-ray diffraction (XRD),
      Thermogravimetric analysis (TGA), Contact angle, and scanning electron microscope
      (SEM). The effects of pH, contact time and equilibrium concentration on the MB
      dye adsorption were investigated batch wise. Optimal conditions were obtained at
      pH?6 due to the generation of negatively charged groups (COO-) in the adsorbent,
      which can strongly interact with the positive charges from MB and time of
      adsorption equilibrium was achieved in 30 min. The XG-cl-PAA/o-MWCNTs hydrogel
      nanocomposite exhibited a very high adsorption potential, and its adsorption
      capacities calculated based on the Langmuir isotherm for MB was 521.0 mg/g at 30 
      degrees C. The dye adsorption data fitted well to the pseudo-first-order model
      and Langmuir model. The adsorption-desorption cycle of hydrogel nanocomposite was
      repeated several times without significant loss of adsorption capacity.

PMID- 29216579
TI  - IR spectra and properties of solid acetone, an interstellar and cometary
      molecule.
AB  - Mid-infrared spectra of amorphous and crystalline acetone are presented along
      with measurements of the refractive index and density for both forms of the
      compound. Infrared band strengths are reported for the first time for amorphous
      and crystalline acetone, along with IR optical constants. Vapor pressures and a
      sublimation enthalpy for crystalline acetone also are reported. Positions of 13C
      labeled acetone are measured. Band strengths are compared to gas-phase values and
      to the results of a density-functional calculation. A 73% error in previous work
      is identified and corrected.

PMID- 29216580
TI  - Microfluidic magnetic fluidized bed for DNA analysis in continuous flow mode.
AB  - Magnetic solid phase substrates for biomolecule manipulation have become a
      valuable tool for simplification and automation of molecular biology protocols.
      However, the handling of magnetic particles inside microfluidic chips for
      miniaturized assays is often challenging due to inefficient mixing, aggregation,
      and the advanced instrumentation required for effective actuation. Here, we
      describe the use of a microfluidic magnetic fluidized bed approach that enables
      dynamic, highly efficient and simplified magnetic bead actuation for DNA analysis
      in a continuous flow platform with minimal technical requirements. We evaluate
      the performance of this approach by testing the efficiency of individual steps of
      a DNA assay based on padlock probes and rolling circle amplification. This assay
      comprises common nucleic acid analysis principles, such as hybridization,
      ligation, amplification and restriction digestion. We obtained efficiencies of up
      to 90% for these reactions with high throughput processing up to 120MUL of DNA
      dilution at flow rates ranging from 1 to 5MUL/min without compromising
      performance. The fluidized bed was 20-50% more efficient than a commercially
      available solution for microfluidic manipulation of magnetic beads. Moreover, to
      demonstrate the potential of this approach for integration into micro-total
      analysis systems, we optimized the production of a low-cost polymer based
      microarray and tested its analytical performance for integrated single-molecule
      digital read-out. Finally, we provide the proof-of-concept for a single-chamber
      microfluidic chip that combines the fluidized bed with the polymer microarray for
      a highly simplified and integrated magnetic bead-based DNA analyzer, with
      potential applications in diagnostics.

PMID- 29216581
TI  - Transfer and persistence of non-self DNA on hands over time: Using empirical data
      to evaluate DNA evidence given activity level propositions.
AB  - Questions relating to how DNA from an individual got to where it was recovered
      from and the activities associated with its pickup, retention and deposition are
      increasingly relevant to criminal investigations and judicial considerations. To
      address activity level propositions, investigators are typically required to
      assess the likelihood that DNA was transferred indirectly and not deposited
      through direct contact with an item or surface. By constructing a series of
      Bayesian networks, we demonstrate their use in assessing activity level
      propositions derived from a recent legal case involving the alleged secondary
      transfer of DNA to a surface following a handshaking event. In the absence of
      data required to perform the assessment, a set of handshaking simulations were
      performed to obtain probabilities on the persistence of non-self DNA on the hands
      following a 40min, 5h or 8h delay between the handshake and contact with the
      final surface (an axe handle). Variables such as time elapsed, and the activities
      performed and objects contacted between the handshake and contact with the axe
      handle, were also considered when assessing the DNA results. DNA from a known
      contributor was transferred to the right hand of an opposing hand-shaker (as a
      depositor), and could be subsequently transferred to, and detected on, a surface
      contacted by the depositor 40min to 5h post-handshake. No non-self DNA from the
      known contributor was detected in deposits made 8h post-handshake. DNA from the
      depositor was generally detected as the major or only contributor in the profiles
      generated. Contributions from the known contributor were minor, decreasing in
      presence and in the strength of support for inclusion as the time between the
      handshake and transfer event increased. The construction of a series of Bayesian
      networks based on the case circumstances provided empirical estimations of the
      likelihood of direct or indirect deposition. The analyses and conclusions
      presented demonstrate both the complexity of activity level assessments
      concerning DNA evidence, and the power of Bayesian networks to visualise and
      explore the issues of interest for a given case.

PMID- 29216582
TI  - Cellular and mitochondrial determination of low molecular mass organic acids by
      LC-MS/MS.
AB  - A selective and sensitive method for the determination of low molecular mass
      organic acids (LMMOAs) in cell and mitochondrial extracts is presented. The
      analytical method consists in the separation by reversed phase liquid
      chromatography and detection with tandem mass spectrometry (LC-MS/MS) of the
      LMMOAs like malic, succinic, formic and citric acids. These acids are among the
      cellular intermediates of the tricarboxylic acid cycle (TCA), thus their
      quantitation can provide essential information about the catabolic and anabolic
      processes occurring in cells under physiological and pathological conditions. The
      analytical method was fully validated in terms of linearity, detection and
      quantification limits, recovery and precision. Detection limits (LOD) for malic,
      succinic and fumaric acids were in the range of 1-10nM, while 20nM was obtained
      for citric acid. Analytical recovery in cell and mitochondrial extracts was found
      between 88 and 105% (CV% <=7.1) and matrix effect was estimated to be less than
      108%. The LC-MS/MS method applied to the quantification of TCA cycle metabolites
      revealed a different distribution of the four acids in cells and mitochondria,
      and it could be used to monitoring metabolic alterations associated with TCA
      cycle and oxidative phosphorylation dysfunctions.

PMID- 29216583
TI  - HPLC-MS/MS analysis of mesupron and its application to a pharmacokinetic study in
      rats.
AB  - Mesupron, the first-in-class inhibitor of urokinase-type plasminogen activator
      (uPA) is known to regulate cell proliferation and migration, and is under
      investigation for the treatment of metastatic breast cancer. In this study, a
      quantification method was developed for the determination of mesupron in rat
      plasma using liquid chromatography with a tandem mass spectrometry (LC-MS/MS).
      After protein precipitation with acetonitrile including itraconazole (internal
      standard, IS), the analytes were chromatographed on a reversed phased column with
      a mobile phase of acetonitrile and water (7:3, v/v, including 0.1% formic acid).
      The ion transitions of the precursor to the product ion were principally
      protonated ion [M+H]+ at m/z 630.4->398.3 for mesupron and 705.2->392.1 for the
      IS. The accuracy and precision of the assay were in accordance with FDA
      regulations for the validation of bioanalytical methods This method was
      successfully applied to a pharmacokinetic study of mesupron after intravenous
      administration in rats.

PMID- 29216584
TI  - Differential scanning calorimetry isothermal hold times can impact
      interpretations of drug-polymer dispersability in amorphous solid dispersions.
AB  - Differential scanning calorimetry (DSC) is a commonly employed analytical
      technique for the analysis and characterization of amorphous solid dispersions.
      However, steps typical of standard temperature programs can alter the material in
      situ. Data for two active pharmaceutical ingredients are detailed, wherein
      isothermal hold times, traditionally employed to remove thermal history and/or
      residual solvent, were observed to impact the observed dispersability of the
      compounds in polyvinylpyrrolidone vinyl-acetate copolymer (PVPva). Re
      crystallized tolbutamide was observed to re-dissolve in PVPva, while terfenadine
      was observed to crystallize during the isothermal hold period. Exposing co
      solidified drug-polymer mixtures to temperature changes and experimental hold
      times can potentially confound correct categorization of dispersability,
      particularly when DSC is used as the lone characterization technique. This work
      illustrates the importance of using a combination of techniques to improve the
      certainty of conclusions made with respect to the true, initial physical state of
      a co-solidified mixture.

PMID- 29216585
TI  - Determination of irinotecan and its metabolite SN-38 in dried blood spots using
      high-performance liquid-chromatography with fluorescence detection.
AB  - Irinotecan (IRI) is an antineoplastic drug widely used for the treatment of
      colorectal and advanced pancreatic cancer. Despite its clinical utility, the
      clinical use of IRI is associated with potentially severe hematopoietic and
      gastrointestinal toxicities. The quantification of IRI and its active metabolite
      SN-38 in dried blood spots (DBS) may be an alternative to individualize the drug
      dose through a minimally invasive and easy collection method. The aim of this
      study was to develop and validate a simple and fast HPLC-FL assay for
      simultaneous IRI and SN-38 measurement in DBS, with adequate analytical
      performance for clinical use. The method employs liquid extraction of one 8mm
      disk of whole blood, followed by separation in a reversed phase Eclipse Plus C8
      column (150*4.6mm, 5MUm). Detection was performed with a fluorescence detector,
      with excitation wavelength of 370 and emission of 420 for IRI and 540nm for SN-38
      and internal standard (camptothecin). Total analytical run time was 17min. Mobile
      phase was a mixture of 0.1M phosphate buffer pH 4.0 and acetonitrile (80:20,
      v/v), at 1mLmin-1. The assay was linear in the range 10-3,000ngmL-1 and from 0.5
      to 300ngmL-1 for IRI and SN-38, respectively. Precision assays presented CV% of
      2.71-5.65 and 2.15-10.07 for IRI and SN-38, respectively, and accuracy in the
      range of 94.26-100.93 and 94.24-99.33%. IRI and SN-38 were stable at 25 and 42
      degrees C for 14days in DBS samples. The method was applied to DBS samples
      obtained from fingerpicks from 19 volunteers receiving IRI in single or combined
      chemotherapy regimens, collected 1 and 24h after beginning of the infusion. The
      estimated plasma concentration of IRI and SN-38 in sample collected 1h after star
      of infusion had 16 of 19 values within the +/-20% range of the measured plasma
      concentrations. On the other hand, predictions of IRI and SN-38 plasma
      concentrations from DBS measurements obtained 24h after the beginning of the
      infusion were poor. AUC of IRI that was calculated using plasma and DBS-estimated
      concentrations, with a high correlation (r=0.918). The method presented suitable
      characteristics for the clinical use. However, translation of IRI and SN-38 DBS
      to plasma concentrations is challenging due to the compound's variable
      plasma/blood partition.

PMID- 29216586
TI  - Non-ionic detergent Triton X-114 Based vortex- synchronized matrix solid-phase
      dispersion method for the simultaneous determination of six compounds with
      various polarities from Forsythiae Fructus by ultra high-performance liquid
      chromatography.
AB  - A simple nonionic detergent - based vortex- synchronized matrix solid-phase
      dispersion (ND-VSMSPD) method was developed to extract bioactive compounds in
      Forsythiae Fructus coupled with ultra high-performance liquid chromatography
      (UHPLC). Nonionic detergent Triton 114 was firstly used as a green elution
      reagent in vortex- synchronized MSPD procedure. The optimum parameters were
      investigated to attain the best results, including Florisil as sorbent, 2mL 10%
      (v/v) nonionic detergent Triton X-114 as the elution reagent, 1:1 of
      sample/sorbent ratio, grinding for 3min, and whirling for 2min. The recoveries of
      the six compounds in Forsythiae Fructus were in the range of 95-104% (RSD <4.6%)
      and the method displayed a good linearity within the range of 0.08-20MUgmL-1 for
      caffeic acid, 0.6-150MUgmL-1 for forsythoside A, 0.4-100MUgmL-1 phillyrin, 0.2
      50MUgmL-1 for quercetin, isorhamnetin and arctigenin (r>=0.999). It was proved
      that the extraction yields of almost all compounds attained by the established
      vortex- synchronized MSPD, which required lower sample, reagent and time, were
      higher than the normal MSPD and the traditional ultrasonic-assisted extraction.
      Consequently, this developed vortex- synchronized MSPD coupled with simple UHPLC
      method could be efficiently applies to extract and analyze the target compounds
      in real Forsythiae Fructus samples.

PMID- 29216587
TI  - Quantification of immobilized protein in pharmaceutical production by bio
      assisted potentiometric multisensor system.
AB  - Quantification of proteins is a key biochemical assay in molecular biology,
      biotechnology, medicine and pharmacology. Protein quantification protocols can be
      based on spectrophotometry, enzyme-linked immunosorbent assay, mass spectrometry
      or quantitative immunoblotting depending on analyte. In case of immobilized
      protein these methods require suitable sample preparation. Thus, sophisticated
      analysis becomes even more complex, expensive and time-consuming. Such drawbacks
      are highly undesirable in industry. In this study we propose a new approach for
      evaluation of immobilized protein concentration based on application of bio
      assisted potentiometric multisensor system. Surface-immobilized recombinant
      protein A from Staphylococcus aureus (SpA, expressed in Escherichia coli), which
      is commonly used as affinity ligand immobilized to stationary phase
      (shromatography media) for monoclonal antibody purification was employed as the
      model object. Chromatography media samples containing different amounts of
      immobilized SpA were analyzed. Proteinase K from Tritirachium album was employed
      as a bio-transducer. We demonstrated that the suggested approach provides
      information about immobilized SpA concentration with 0.8mg/ml accuracy in the
      range 1-6.7mg/ml and within just 16min. Moreover, the proposed procedure requires
      no expensive materials and equipment and no bio-transducer immobilization. This
      method has potential of application for fast monitoring of other immobilized
      proteins in different tasks.

PMID- 29216588
TI  - NMR study of mutations of glycine-52 of the catalytic domain of diphtheria toxin.
AB  - Cross-reacting-material 197 (CRM197) is a naturally occurring non-toxic mutant of
      diphtheria toxin (DT) that is one of the few carrier protein used in the
      manufacture of polysaccharide vaccines targeting bacterial pathogens such as
      Neisseria meningitidis, Streptococcus pneumaniae and Haemophilus influenzae. A
      detailed explanation in structural terms for the lack of toxicity has started to
      emerge with the report of the X-ray structure of CRM197. Here, we present an NMR
      spectroscopy study of the wild-type catalytic domain of diphtheria toxin and the
      effects of mutations at residue 52 on its conformation. We utilized a strategy
      that consisted of gradually inducing steric perturbations by increasing the side
      chain size of the residue. Results show that the catalytic domain does not
      tolerate even the smallest perturbation, such as a glycine to alanine
      substitution, resulting in the destabilization of domain fold leading to protein
      aggregation. The observed behavior is further exacerbated with the substitution
      of amino acids with larger side chains. These findings support the concept that
      the lack of toxicity observed for CRM197 is the result of a highly unstable
      conformation of its catalytic domain that, upon insertion into the cell, cannot
      properly refold and perform its catalytic activity responsible for the arrest of
      all cellular protein synthesis.

PMID- 29216589
TI  - Comparing dried and liquid blood serum samples of depressed patients: An analysis
      by Raman and infrared spectroscopy methods.
AB  - Depression is a serious mental illness. To study the mechanism of depression and
      search for new, more effective therapies, animal models are often used.
      Unfortunately, none of the available models reflects all the symptoms of
      depression. Therefore researchers are looking for new tools to diagnose
      depression. Unfortunately, the nowadays-available depression diagnosis methods
      are only psychological tests. However, it is known, that the amount of
      phospholipids, proteins and lipids decreases during depression. Raman and FTIR
      (Fourier Transform Infra Red) spectroscopies provide information on the chemical
      compounds in the measured sample e.g. blood serum. These spectroscopic techniques
      may thus become reliable and accurate tools for evaluating changes in the amount
      of phospholipids and proteins in depression disease. In this study differences
      between dried and liquid blood serum samples of healthy and depressed individuals
      measured by Raman (range 0-3000cm-1) and FTIR (Fourier Transform Infrared) (range
      900-3000cm-1) spectroscopy were evaluated. The resulting spectra and accurate
      analysis led to the conclusion that an appropriate measurement of the background
      and the elimination of peaks from water had the greatest impact on the
      reliability of the results. Furthermore, after detailed studies of FTIR and Raman
      spectra of dried and liquid blood serum samples, including a complete analysis of
      peaks after Kramers-Kroning (KK) transformation, it was found that the sample
      preparation did not affect the results obtained by Raman spectroscopy. In FTIR
      measurements only a minimal effect on peak intensity was observed.

PMID- 29216590
TI  - Improved bioautographic assay on TLC layers for qualitative and quantitative
      estimation of xanthine oxidase inhibitors and superoxide scavengers.
AB  - A new agar-free bioautographic assay for xanthine oxidase (XO) inhibitors and
      superoxide scavengers on TLC layers was developed and validated. Compared to the
      first version of TLC bioautographic agar overlay method, our bioautographic assay
      greatly improved the sensitivity and quantification ability. The limit of
      detection (LOD) of this assay was 0.017ng for allopurinol. Quantitative
      estimation of XO inhibitors and superoxide scavengers was achieved by
      densitometry scanning, expressed as allopurinol equivalents in millimoles on a
      per sample weight basis. This assay has acceptable accuracy (95.37-99.23%), intra
      day and inter-day precisions (RSD, 2.56-6.69%), as well as intra-plate and inter
      plate precisions (RSD, 2.93-9.62%). Six pure compounds and three herbal extracts
      were evaluated for their potential XO inhibitory and superoxide scavenging
      activity by this bioautographic assay on TLC layers. Four active components were
      separated, located and identified in Astragalus membranaceus var. mongholicus
      extract by the bioautographic assay after TLC separation. The developed method is
      rapid, simple, sensitive and stable for screening and estimation of the potential
      XO inhibitors and superoxide scavengers.

PMID- 29216591
TI  - Concomitant monitoring of implant formation and drug release of in situ forming
      poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the
      subcutis using UV-vis imaging.
AB  - For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the
      rate of implant formation plays an important role in determining the overall drug
      release kinetics. Currently, in vitro techniques capable of characterizing the
      processes of drug release and implant formation at the same time are not
      available. A hydrogel-based in vitro experimental setup was recently developed
      requiring only microliter of formulation and forming a closed system potentially
      suitable for interfacing with various spectroscopic techniques. The aim of the
      present proof-of-concept study was to investigate the feasibility of concomitant
      UV imaging, Vis imaging and light microscopy for detailed characterization of the
      behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the
      subcutis. The model compounds, piroxicam and alpha-lactalbumin were added to PLGA
      1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA
      solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and
      light microscopy were applied to visualize the depot formation and UV imaging was
      used to quantify drug transport in the hydrogel. As compared to piroxicam, the
      alpha-lactalbumin invoked an acceleration of phase separation and an increase of
      implant size. alpha-Lactalbumin was released faster from the PLGA-1-methyl-2
      pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam
      release pattern. A linear relationship between the rate of implant formation and
      initial compound release within the first 4h was established for the PLGA-NMP
      systems. This implies that phase separation may be one of the controlling factors
      in drug release. The rate of implant formation may be an important parameter for
      predicting and tailoring drug release. The approach combining UV imaging, Vis
      imaging and light microscopy may facilitate understanding of release processes
      and holds potential for becoming a useful tool in formulation development of in
      situ forming implants.

PMID- 29216592
TI  - Activated carbon thin-layer placement as an in situ mercury remediation tool in a
      Penobscot River salt marsh.
AB  - The efficacy of thin layer in situ soil amendments was tested as a potential tool
      for methylmercury (MeHg) risk mitigation in Penobscot River, ME, salt marsh. Salt
      marshes are sites of high MeHg accumulation within the Penobscot, and key targets
      for remediation. The study was a fully-crossed small plot study, with four
      treatments (activated carbon (AC), biochar, FeCl2, and lime) and unamended
      controls at two sites. Plots were monitored for two years. Porewater MeHg
      concentrations were the main endpoint, with impacts on sediment biogeochemistry
      as a secondary study goal. AC-based SediMiteTM was effective in reducing MeHg,
      and to a less extent total Hg, in surficial pore waters. AC reduced MeHg
      concentrations by >90% at the one month time point, and continued to
      significantly reduce pore water MeHg through about a year. AC was less effective
      in reducing total Hg in pore water, yielding about 70% reduction at one month,
      and 50-65% reduction at 8months. Biochar provided lower, and more variable
      reduction in porewater MeHg, but was not effective in reducing total Hg. Biochar
      amendment also increased soil MeHg. Neither FeCl2 nor lime amendments reduced
      pore water Hg or MeHg levels. About 50% of AC treatment applied as SediMiteTM
      pellets was retained in marsh soils after one year. This study is one of the
      first field trials of in situ amendment for MeHg remediation. Our results show
      that thin-layer AC placement is a potential remediation tool for Hg risk to
      biota, especially in marshes where net MeHg accumulation is often strong.

PMID- 29216593
TI  - Phosphorus and nitrogen limitation and impairment of headwater streams relative
      to rivers in Great Britain: A national perspective on eutrophication.
AB  - This study provides a first national-scale assessment of the nutrient status of
      British headwater streams within the wider river network, by joint analysis of
      the national Countryside Survey Headwater Stream and Harmonised River Monitoring
      Scheme datasets. We apply a novel Nutrient Limitation Assessment methodology to
      explore the extent to which nutrients may potentially limit primary production in
      headwater streams and rivers, by coupling ternary assessment of nitrogen (N),
      phosphorus (P), and carbon (C) depletion, with N:P stoichiometry, and threshold P
      and N concentrations. P limitation was more commonly seen in the rivers, with
      greater prevalence of N limitation in the headwater streams. High levels of
      potential P and N co-limitation were found in the headwater streams, especially
      the Upland-Low-Alkalinity streams. This suggests that managing both P and N
      inputs may be needed to minimise risks of degradation of these sensitive
      headwater stream environments. Although localised nutrient impairment of
      headwater streams can occur, there were markedly lower rates of P and N
      impairment of headwater streams relative to downstream rivers at the national
      scale. Nutrient source contributions, relative to hydrological dilution,
      increased with catchment scale, corresponding with increases in the extent of
      agricultural and urban land-use. The estimated nutrient reductions needed to
      achieve compliance with Water Framework Directive standards, and to reach
      limiting concentrations, were greatest for the Lowland-High-Alkalinity rivers and
      streams. Preliminary assessments suggest that reducing P concentrations in the
      Lowland-High-Alkalinity headwater streams, and N concentrations in the Upland-Low
      Alkalinity rivers, might offer greater overall benefits for water-quality
      remediation at the national scale, relative to the magnitude of nutrient
      reductions required. This approach could help inform the prioritisation of
      nutrient remediation, as part of a directional approach to water quality
      management based on closing the gaps between current and target nutrient
      concentrations.

PMID- 29216594
TI  - Indicators to support healthy urban gardening in urban management.
AB  - Urban gardening is part of a trend towards more parks and green areas in cities,
      consumption of organic, locally grown products, and a closer relationship with
      one's own living environment. Our literature review shows that urban gardens
      provide opportunities for physical activity and allow people to consume homegrown
      fruit and vegetables. Urban gardens may also reduce stress levels of gardeners
      and improve social cohesion. In this way, they can help to prevent health
      problems. Good quality of urban soil and the functioning of soil ecosystems are
      indispensable prerequisites for these. We developed a framework that shows how
      ecosystem health and human health are interconnected in urban gardening, by
      placing it in the context of urban green space management and valuation. This
      study yields a set of indicators, which can be used to assess soil ecosystem
      services and health impacts. They may provide a basis for the evolving dialogue
      in decision-making processes and partnership activities in urban management.
      Recognizing the potential effects and discussing what is important to whom, might
      be enough to find synergies. Importantly, the initiators of urban gardens are
      often citizens, who seek support from other stakeholders. The social network
      established by gardens may contribute to health-enabling, cohesive communities
      involved with their living environment. To maximize health benefits, it is useful
      to make the urban gardens accessible to many people. This study suggests that
      urban gardens deserve a position in urban green space management as they may help
      to address societal challenges like urbanization, health and well-being in aging
      populations and climate adaptation.

PMID- 29216595
TI  - Optimizing prescribed fire allocation for managing fire risk in central
      Catalonia.
AB  - We used spatial optimization to allocate and prioritize prescribed fire
      treatments in the fire-prone Bages County, central Catalonia (northeastern
      Spain). The goal of this study was to identify suitable strategic locations on
      forest lands for fuel treatments in order to: 1) disrupt major fire movements, 2)
      reduce ember emissions, and 3) reduce the likelihood of large fires burning into
      residential communities. We first modeled fire spread, hazard and exposure
      metrics under historical extreme fire weather conditions, including node
      influence grid for surface fire pathways, crown fraction burned and fire
      transmission to residential structures. Then, we performed an optimization
      analysis on individual planning areas to identify production possibility
      frontiers for addressing fire exposure and explore alternative prescribed fire
      treatment configurations. The results revealed strong trade-offs among different
      fire exposure metrics, showed treatment mosaics that optimize the allocation of
      prescribed fire, and identified specific opportunities to achieve multiple
      objectives. Our methods can contribute to improving the efficiency of prescribed
      fire treatment investments and wildfire management programs aimed at creating
      fire resilient ecosystems, facilitating safe and efficient fire suppression, and
      safeguarding rural communities from catastrophic wildfires. The analysis
      framework can be used to optimally allocate prescribed fire in other fire-prone
      areas within the Mediterranean region and elsewhere.

PMID- 29216596
TI  - Understanding social and behavioral drivers and impacts of air quality sensor
      use.
AB  - BACKGROUND: Lower-cost air quality sensors (hundreds to thousands of dollars) are
      now available to individuals and communities. This technology is undergoing a
      rapid and fragmented evolution, resulting in sensors that have uncertain data
      quality, measure different air pollutants and possess a variety of design
      attributes. Why and how individuals and communities choose to use sensors is
      arguably influenced by social context. For example, community experiences with
      environmental exposures and health effects and related interactions with industry
      and government can affect trust in traditional air quality monitoring. To date,
      little social science research has been conducted to evaluate why or how sensors,
      and sensor data, are used by individuals and communities, or how the introduction
      of sensors changes the relationship between communities and air quality managers.
      OBJECTIVES: This commentary uses a risk governance/responsible innovation
      framework to identify opportunities for interdisciplinary research that brings
      together social scientists with air quality researchers involved in developing,
      testing, and deploying sensors in communities. DISCUSSION: Potential areas for
      social science research include communities of sensor users; drivers for use of
      sensors and sensor data; behavioral, socio-political, and ethical implications of
      introducing sensors into communities; assessing methods for communicating sensor
      data; and harnessing crowdsourcing capabilities to analyze sensor data.
      CONCLUSIONS: Social sciences can enhance understanding of perceptions, attitudes,
      behaviors, and other human factors that drive levels of engagement with and trust
      in different types of air quality data. New transdisciplinary research bridging
      social sciences, natural sciences, engineering, and design fields of study, and
      involving citizen scientists working with professionals from a variety of
      backgrounds, can increase our understanding of air sensor technology use and its
      impacts on air quality and public health.

PMID- 29216597
TI  - Role of Dopamine Receptors in the Anticancer Activity of ONC201.
AB  - ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes
      early activation of the integrated stress response. Its promising safety profile
      and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in
      several advanced malignancies. Binding and reporter assays have shown that ONC201
      is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2
      and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in
      ONC201's anticancer effects. Using cBioportal and quantitative reverse
      transcription polymerase chain reaction analyses, we confirmed that DRD2 is
      expressed in different cancer cell types in a cell type-specific manner. On the
      other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with
      low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and
      correlated with an increase in ONC201-induced CHOP mRNA expression. On the other
      hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not
      sufficient to abrogate ONC201's anticancer effects. Although ONC201's anticancer
      activity was not dependent on DRD2 expression in the cancer cell types tested, we
      assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in
      HCT116 cells activated the integrated stress response and reduced cell number.
      Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we
      demonstrate in this study that disrupting dopamine receptor expression and
      activity can have cytotoxic effects that may at least be in part due to the
      activation of the integrated stress response. On the other hand, ONC201's
      anticancer activity goes beyond its ability to antagonize DRD2, potentially due
      to ONC201's ability to activate other pathways that are independent of DRD2.
      Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of
      a pharmacological antagonist promoted ONC201-induced anticancer activity.

PMID- 29216599
TI  - Boson peak dynamics of natural polymer starch investigated by terahertz time
      domain spectroscopy and low-frequency Raman scattering.
AB  - Terahertz time-domain spectroscopy and low-frequency Raman scattering were
      performed on the natural polymer starch to investigate the boson peak (BP)
      dynamics. In the infrared spectrum, the BP was observed at 0.99THz at the lowest
      temperature. Compared to the result from a previous study for vitreous glucose,
      both the frequency of the BP and absorption coefficient show lower values than
      those of the vitreous glucose. These behaviors originate from the longer
      correlation length of the medium-range order and lower concentration of hydroxyl
      groups in the starch. In the Raman spectrum, the BP was observed at 1.1THz at
      room temperature, although the BP was not observed around room temperature due to
      the excess wing of the fast relaxation modes in the infrared spectrum. The
      temperature dependence of epsilon"(nu) during the heating process and cooling
      process shows a hysteresis below 230K. During the heating process, kinks were
      observed at 140K and 230K. These kinks are attributed to the beta-relaxation and
      the betawet-relaxation, respectively.

PMID- 29216598
TI  - Sympathetic nervous system activity measured by skin conductance quantifies the
      challenge of walking adaptability tasks after stroke.
AB  - BACKGROUND: Walking adaptability tasks are challenging for people with motor
      impairments. The construct of perceived challenge is typically measured by self
      report assessments, which are susceptible to subjective measurement error. The
      development of an objective physiologically-based measure of challenge may help
      to improve the ability to assess this important aspect of mobility function. The
      objective of this study to investigate the use of sympathetic nervous system
      (SNS) activity measured by skin conductance to gauge the physiological stress
      response to challenging walking adaptability tasks in people post-stroke.
      METHODS: Thirty adults with chronic post-stroke hemiparesis performed a battery
      of seventeen walking adaptability tasks. SNS activity was measured by skin
      conductance from the palmar surface of each hand. The primary outcome variable
      was the percent change in skin conductance level (DeltaSCL) between the baseline
      resting and walking phases of each task. Task difficulty was measured by
      performance speed and by physical therapist scoring of performance. Walking
      function and balance confidence were measured by preferred walking speed and the
      Activities-specific Balance Confidence Scale, respectively. RESULTS: There was a
      statistically significant negative association between DeltaSCL and task
      performance speed and between DeltaSCL and clinical score, indicating that tasks
      with greater SNS activity had slower performance speed and poorer clinical
      scores. DeltaSCL was significantly greater for low functioning participants
      versus high functioning participants, particularly during the most challenging
      walking adaptability tasks. CONCLUSION: This study supports the use of SNS
      activity measured by skin conductance as a valuable approach for objectively
      quantifying the perceived challenge of walking adaptability tasks in people post
      stroke.

PMID- 29216600
TI  - Ethylene formation by dehydration of ethanol over medium pore zeolites.
AB  - In this work, the role of pore arrangement of 10-ring zeolites ZSM-5, TNU-9 and
      IM-5 on their catalytic properties in ethanol transformation were investigated.
      Among all the studied catalysts, the zeolite IM-5, characterized by limited 3
      dimensionality, presented the highest conversion of ethanol and the highest
      yields of diethyl ether (DEE) and ethylene. The least active and selective to
      ethylene and C3+ products was zeolite TNU-9 with the largest cavities formed on
      the intersection of 10-ring channels. The catalysts varied, however, in lifetime,
      and their deactivation followed the order: IM-5>TNU-9>ZSM-5. The processes taking
      place in the microporous zeolite environment were tracked by IR spectroscopy and
      analysed by the 2D correlation analysis (2D COS) allowing for an insight into the
      nature of chemisorbed adducts and transition products of the reaction. The cage
      dimension was found as a decisive factor influencing the tendency for coke
      deposition, herein identified as polymethylated benzenes, mainly 1,2,4-trimethyl
      benzene.

PMID- 29216601
TI  - Measuring critical thinking in pre-registration midwifery students: A multi
      method approach.
AB  - OBJECTIVE: Test the concurrent validity of three newly developed tools (student
      self-rating, preceptor rating, and reflective writing) that aim to measure
      critical thinking in midwifery practice. DESIGN: A descriptive matched cohort
      design was used. SETTING: Australian research intensive university offering a
      three year Bachelor of Midwifery programme. SAMPLE: Fifty-five undergraduate
      midwifery students. METHODS: Students assessed their ability to apply critical
      thinking in midwifery practice using a 25-item tool and a 5-item subscale in
      Motivated Strategies for Learning Questionnaire. Clinical preceptors completed a
      24-item tool assessing the students' application of critical thinking in
      practice. Reflective writing by students was assessed by midwifery academics
      using a 15-item tool. Internal reliability, and concurrent validity were
      assessed. Correlations, t-tests, multiple regression and confidence levels were
      calculated for the three scales and associations with student characteristics.
      RESULTS: The three scales achieved good internal reliability with a Cronbach's
      alpha coefficient between 0.93 and 0.97. Matched total scores for the three
      critical thinking scales were moderately correlated; student/preceptor (r=0.36,
      p<0.01); student/reflective writing (r=0.38, p<0.01); preceptor/reflective
      writing (r=0.30, p<0.05). All critical thinking mean scores were higher for
      students with a previous degree, but only significant for reflective writing (t
      (53)=-2.35, p=0.023). Preceptor ratings were predictive of GPA (beta=0.50,
      p<0.001, CI=0.10 to 0.30). Students' self-rating scores were predictive of year
      level (beta=0.32, p<0.05, CI=0.00 to 0.03). CONCLUSION: The student, preceptor,
      and reflective writing tools were found to be reliable and valid measures of
      critical thinking. The three tools can be used individually or in combination to
      provide students with various sources of feedback to improve their practice. The
      tools allow formative measurement of critical thinking over time. Further testing
      of the tools with larger, diverse samples is recommended.

PMID- 29216602
TI  - Nursing students learning the pharmacology of diabetes mellitus with complexity
      based computerized models: A quasi-experimental study.
AB  - BACKGROUND: Pharmacology is a crucial component of medications administration in
      nursing, yet nursing students generally find it difficult and self-rate their
      pharmacology skills as low. OBJECTIVES: To evaluate nursing students learning
      pharmacology with the Pharmacology Inter-Leaved Learning-Cells environment, a
      novel approach to modeling biochemical interactions using a multiscale, computer
      based model with a complexity perspective based on a small set of entities and
      simple rules. This environment represents molecules, organelles and cells to
      enhance the understanding of cellular processes, and combines these cells at a
      higher scale to obtain whole-body interactions. PARTICIPANTS: Sophomore nursing
      students who learned the pharmacology of diabetes mellitus with the Pharmacology
      Inter-Leaved Learning-Cells environment (experimental group; n=94) or via a
      lecture-based curriculum (comparison group; n=54). METHODS: A quasi-experimental
      pre- and post-test design was conducted. The Pharmacology-Diabetes-Mellitus
      questionnaire and the course's final exam were used to evaluate students'
      knowledge of the pharmacology of diabetes mellitus. RESULTS: Conceptual learning
      was significantly higher for the experimental than for the comparison group for
      the course final exam scores (unpaired t=-3.8, p<0.001) and for the Pharmacology
      Diabetes-Mellitus questionnaire (U=942, p<0.001). The largest effect size for the
      Pharmacology-Diabetes-Mellitus questionnaire was for the medication action
      subscale. Analysis of complex-systems component reasoning revealed a significant
      difference for micro-macro transitions between the levels (F(1, 82)=6.9, p<0.05).
      CONCLUSIONS: Learning with complexity-based computerized models is highly
      effective and enhances the understanding of moving between micro and macro levels
      of the biochemical phenomena, this is then related to better understanding of
      medication actions. Moreover, the Pharmacology Inter-Leaved Learning-Cells
      approach provides a more general reasoning scheme for biochemical processes,
      which enhances pharmacology learning beyond the specific topic learned. The
      present study implies that deeper understanding of pharmacology will support
      nursing students' clinical decisions and empower their proficiency in medications
      administration.

PMID- 29216603
TI  - Effects of an intensive clinical skills course on senior nursing students' self
      confidence and clinical competence: A quasi-experimental post-test study.
AB  - BACKGROUND: To foster nursing professionals, nursing education requires the
      integration of knowledge and practice. Nursing students in their senior year
      experience considerable stress in performing the core nursing skills because,
      typically, they have limited opportunities to practice these skills in their
      clinical practicum. Therefore, nurse educators should revise the nursing
      curricula to focus on core nursing skills. OBJECTIVES: To identify the effect of
      an intensive clinical skills course for senior nursing students on their self
      confidence and clinical competence. DESIGN: A quasi-experimental post-test study.
      SETTINGS: A university in South Korea during the 2015-2016 academic year.
      PARTICIPANTS: A convenience sample of 162 senior nursing students. METHODS: The
      experimental group (n=79) underwent the intensive clinical skills course, whereas
      the control group (n=83) did not. During the course, students repeatedly
      practiced the 20 items that make up the core basic nursing skills using clinical
      scenarios. Participants' self-confidence in the core clinical nursing skills was
      measured using a 10-point scale, while their clinical competence with these
      skills was measured using the core clinical nursing skills checklist. Independent
      t-test and chi-square tests were used to analyze the data. RESULTS: The mean
      scores in self-confidence and clinical competence were higher in the experimental
      group than in the control group. CONCLUSION: This intensive clinical skills
      courses had a positive effect on senior nursing students' self-confidence and
      clinical competence for the core clinical nursing skills. This study emphasizes
      the importance of reeducation using a clinical skills course during the
      transition from student to nursing professional.

PMID- 29216604
TI  - Digital holographic microscopy for 3D surface characterization of polymeric
      nanocomposites.
AB  - The aim of this paper is to introduce digital holographic microscopy (DHM) as a
      non-contact, inexpensive, and non-abrasive method for 3D surface characterization
      of polymeric nanocomposites. A common-path and vibration-immune Mirau system with
      a microsphere-assisted arrangement is utilized to increase the lateral resolution
      of the images. The characterization is performed through the measurement of
      roughness parameters of the surfaces, which are derived from the recorded
      holograms. Pure poly(triazole-amide-imide) (PTAI) and PTAI nanocomposite
      reinforeced with surface modified TiO2 nanoparticles (MN-TiO2) are used and
      compared. The experimental results show the potential of the presented method to
      serve as an alternative for expensive surface measurement devices such as stylus
      profiler and atomic force microscope (AFM) for polymeric surface
      characterization.

PMID- 29216605
TI  - Gluten peptides drive healthy and celiac monocytes toward an M2-like
      polarization.
AB  - Celiac disease (CD) is an immune-mediated enteropathy triggered by ingested
      gluten in genetically susceptible individuals and sustained by both adaptive and
      innate immune responses. Recent studies in murine macrophages demonstrated that
      the activation of arginase (ARG) metabolic pathway by gluten peptides contributes
      to the modulation of intestinal permeability in vitro. Here we characterize the
      effects of gluten on arginine metabolism and cell polarization in human monocytes
      from both healthy and CD subjects; both a simplified enzymatic digestion of
      gliadin and a physiological digestion of whole wheat have been tested. Results
      indicate that gluten digests induce the onset of an M2-like phenotype in
      activated macrophages; more precisely, both isoforms of arginase, ARG1 and ARG2,
      are induced likely due to the inhibition of mTOR and the consequent induction of
      C/EBPbeta transcription factor. These effects are independent from the origin of
      gluten as well as from the digestive protocol employed; moreover, no statistical
      difference can be evidenced between healthy and CD patients, excluding a diverse
      predisposition of CD monocytes to gluten-triggered polarization with respect to
      healthy immune cells. Overall, the present findings sustain a role for arginase
      pathway in the immune response elicited by human monocytes toward ingested gluten
      that, hence, deserves particular attention when addressing the pathogenesis of
      CD.

PMID- 29216606
TI  - First- and second-line pharmacological treatment for delirium in general hospital
      setting-Retrospective analysis.
AB  - AIM: We examined the first- and second-line pharmacological treatment for
      delirium to determine which drugs were chosen, how and when second-line drugs
      were started, and the effectiveness and tolerability of those treatments.
      METHODS: A retrospective medical chart review was performed for delirium
      inpatients referred to the Department of Psychiatry, Hiroshima Citizens Hospital,
      from October 2011 to September 2012. Clinical diagnoses were based on ICD-10. We
      compared the baseline severity of delirium, duration needed for improvement, and
      rescue with antipsychotics between subjects given only first-line drugs and those
      switched to second-line drugs. RESULTS: We studied 194 consecutive patients
      including 127 men and 67 women whose average age was 76.5+/-9.8years. For first
      line drugs, trazodone was most frequently prescribed (n=100, 51.5%), followed by
      quetiapine (n=57, 29.4%). Among patients treated with trazodone or quetiapine as
      first line treatment, 59 of 100 (59%) continued trazodone and 52 of 57 (91.2%)
      continued quetiapine. Duration needed for improvement did not differ
      significantly between patients treated with trazodone as a first line drug and
      those with quetiapine as same. CONCLUSION: Trazodone can be a candidate drug as
      one of the first line drugs for delirium.

PMID- 29216607
TI  - Frequency of risk factors and coexisting abnormalities in a population of
      Egyptian children with autism spectrum disorder.
AB  - BACKGROUND: Many risk factors interact together during the critical period of
      development and govern the future phenotype of autism spectrum disorder (ASD).
      Furthermore, co-occurring abnormalities among individuals with ASD vary a lot so
      as their abilities. AIM OF WORK: To investigate possible risk factors and to
      determine the prevalence of coexisting abnormalities in a sample of Egyptian ASD
      children and their influence on the severity and their communication performance.
      METHODS: The diagnosis and severity of ASD for participants (N=80) was performed
      by DSM-5, ADIR and CARS. They were investigated regarding the possible risk
      factors and coexisting abnormalities. A detailed history taking, clinical
      examination, the Arabic preschool language scale, cognitive abilities assessment
      and other additional instrumental measures such as EEG were used. RESULTS:
      Caesarian section and neonatal jaundice were the most common risk factors. The
      severity of ASD was positively related to maternal and paternal ages.
      Developmental language disorder, intellectual disability, attention deficit
      hyperactivity disorder, sleep disorder and EEG changes were more frequently
      detected among studied cases. The CARS scores were significantly higher in ADHD
      and EEG changes groups. The most severely affected CARS items in the groups with
      these disorders were determined. CONCLUSION: High parental ages has an impact on
      the severity of ASD. ADHD, sleep disorder, and EEG changes seem to have an impact
      on certain elements of the adaptive behavior especially the communicative
      performance of ASD individuals. We recommend to seriously investigate co-morbid
      abnormalities and consider them during the process of management of ASD for
      proper intervention plans.

PMID- 29216608
TI  - Short term effects of brief need based psychoeducation on knowledge, self-stigma,
      and burden among siblings of persons with schizophrenia: A prospective controlled
      trial.
AB  - Siblings of persons with schizophrenia are important in providing long-term
      social support to the patients. Interventions addressing their needs are very
      sparse. Hence, this study aimed at testing the short-term effects of brief need
      based psychoeducation on knowledge, self-stigma, and burden among siblings of
      persons with schizophrenia. In this prospective controlled open label trial, 80
      siblings of persons with schizophrenia were allocated in equal numbers to the
      brief need based psychoeducation group and the treatment-as-usual group. The
      outcomes were measured at baseline, and after the first and third month post
      intervention. RM-ANCOVA was conducted to test the effect of the brief
      psychoeducation on outcome scores. The groups were similar with respect to socio
      demographic, clinical, and outcome scores at the baseline. There was a
      significant group*time interaction effect on knowledge (F=8.71; p<0.01;
      etap2=0.14) and self-stigma scores (F=14.47; p<0.001; etap2=0.21), wherein the
      brief psychoeducation group showed a significant increase in knowledge and
      reduction in self-stigma with medium effect size through baseline to the third
      month follow-up as compared to the treatment as usual group. We also observed a
      significant main effect of time; irrespective of the group allocation, there was
      a significant increase in the knowledge through baseline to third month follow-up
      (F=5.69; p=0.02; etap2=0.09). No main or interaction effects of group and time
      were observed on burden. The findings suggest that brief need based
      psychoeducation may increase knowledge about the illness and reduce self-stigma.
      Further systematic studies are warranted to test this intervention for long-term
      effects.

PMID- 29216610
TI  - PreScription: 2017 Pharmacy Compounding Issues: The U.S. Food and Drug
      Administration, Harzardous Drugs, and Wasted Drugs.

PMID- 29216609
TI  - What kinds of factors affect the academic outcomes of university students with
      mental disorders? A retrospective study based on medical records.
AB  - AIMS: University students that suffer from mental disorders seem to have
      difficulty graduating. Therefore, we investigated risk and protective factors of
      dropping out with the aim of improving such students' academic outcomes. METHODS:
      First, we statistically compared the academic outcomes of 203 undergraduate
      students who received treatment in the Department of Psychiatry of the Tsukuba
      University Health Center to those of matched controls. Second, clinical factors
      of 370 mentally ill students were statistically compared between the dropout and
      graduate groups. RESULTS: Mentally ill students experienced significantly greater
      difficulties graduating. Furthermore, the ratio of females and the year of study
      at initial consultation were significantly lower in the dropout group. However,
      duration of illness, social withdrawal, temporary leaves of absence, percentage
      of diagnosis of F2, history of truancy, CGI-S/GI score, number of suicide
      attempts, visits to us, family consultations with us and grade repeating were
      longer or greater in the dropout group. Ultimately, the number of suicide
      attempts, CGI-S score, social withdrawal and leaves of absence were significantly
      associated with dropping out. Moreover, duration of social withdrawal and leaves
      of absence were significantly correlated with CGI-GI score. CONCLUSION: We found
      that the number of suicide attempts, CGI-S score, social withdrawal and extended
      enrollment were risk factors for dropping out, while the therapeutic effect
      seemed to be a protective factor. As risk factors involved states of social
      maladjustment, it is necessary not only to treat mental disorders, but also to
      provide assistance such as educational and individual support for daily living.

PMID- 29216611
TI  - Compounding Opportunities in Urology.
AB  - There are a lot of options that pharmacists, including compounding pharmacists,
      can offer urologists to assist their patients. Compounding pharmacists are in a
      great position to offer unique, effective preparations for many of the conditions
      urologists treat on a daily basis. It would be well worth the time to learn a
      little about the conditions these specialists treat and become familiar with what
      you can offer.

PMID- 29216612
TI  - Child-safety Containers/Devices and Compounding.
AB  - The U.S. Consumer Product Safety Commission has been around since it was created
      in 1972 through the Consumer Product Safety Act. Its purpose is to protect
      "against unreasonable risks of injuries associated with consumer products."
      Manufactured drugs must meet the standards unless specifically exempted.
      Dispensing and compounding pharmacists must also meet the standards. Due to a
      smaller market size, compliant products to meet the U.S. Consumer Product Safety
      Commission's standards to aid compounding pharmacists have been slow in coming.
      However, now there are numerous different products, some introduced recently,
      which make it easier for compounding pharmacists to comply with the standards.
      The new technologies are innovative and serve a great need.

PMID- 29216614
TI  - IACP Legislative/Regulatory Update.

PMID- 29216613
TI  - Documentation: Records and Reports.
AB  - This article deals with documentation to include the beginning of documentation,
      the requirements of Good Manufacturing Practice reports and records, and the
      steps that can be taken to minimize Good Manufacturing Practice documentation
      problems. It is important to remember that documentation for 503a compounding
      involves the Formulation Record, Compounding Record, Standard Operating
      Procedures, Safety Data Sheets, etc. For 503b outsourcing facilities, compliance
      with Current Good Manufacturing Practices is required, so this article is
      applicable to them. For 503a pharmacies, one can see the development and
      modification of Good Manufacturing Practice and even observe changes as they are
      occurring in 503a documentation requirements and anticipate that changes will
      probably continue to occur.

PMID- 29216615
TI  - Quality Control: Bar Codes and Bar Code Scanners for Unit-Dose Medications in a
      Healthcare Setting.

PMID- 29216616
TI  - Basics of Compounding: 3D Printing--Pharmacy Applications: Geometric Shape
      Effects on 3D Printing.
AB  - As patient therapy becomes more specialized and individualized, one applicable
      method of drug delivery is through 3D printing. With 3D printing, pharmacists can
      provide either immediate or modified drug release of either an individual drug or
      multiple drugs in a singledosage unit. The release rates can be varied, not only
      by excipients in the formulation, but also to some extent by the shapes of the
      finished-drug preparation. Some studies demonstrating these concepts are included
      in this article, along with their method of compounding using 3D printing.

PMID- 29216617
TI  - Basics of Sterile Compounding: Particulate Matter.
AB  - This article focuses on the requirements for particulate matter in sterile
      products. Topics include particles and quality, particulate matter standards
      (large- and small-volume injectables), development of the small-volume injectable
      test, electronic (light obscuration) and microscope testing, and special
      requirements for particulate matter in biopharmaceutical preparations.

PMID- 29216618
TI  - Kinetic Analysis of Drug Release from Compounded Slow-release Capsules of
      Liothyronine Sodium (T3).
AB  - The purpose of this study was to formulate extemporaneously compounded
      Liothyronine Sodium (T3) slow-release capsules and to evaluate their in vitro
      drug release performance. Twenty-one formulations containing T3 (7.5 ug) with
      various compositions of two different grades of Methocel E4M and K100M premium
      (30% to 90%), and/or SimpleCap/Lactose (10% to 70%) were examined. Quality
      assessment of the capsules was conducted by standard quality control criteria of
      the United States Pharmacopeia (i.e., weight variation, content uniformity) to
      ensure their compliance. The dissolution release profile of the formulations was
      evaluated using United States Pharmacopeia Apparatus type II (paddle method) at a
      speed of 50 rpm and temperature of 37 degrees C in phosphate buffered saline
      media ( pH = 7.2 to 7.4). Aliquots from the media were taken periodically up to
      24 hours and analyzed using a validated enzyme-linked immunosorbent assay method.
      The cumulative percentage of drug release for each formulation was fitted to
      eleven major release kinetic equations to determine the best-fit model of drug
      release, as well as the mechanism of release. Assay sensitivity was as low as 1
      ng/mL and the optimal calibration range was found to be between 0 ng/mL and 7.5
      ng/mL, which corresponded well with the average physiological plasma
      concentrations of T3. Liothyronine sodium with either SimpleCap (100%) or
      Methocel E4M (100%) exhibited slowrelease kinetic patterns of Peppas and Zero
      Order, respectively. The formulation with SimpleCap (100%) had a higher
      percentage of drug release (as compared to 100% Methocel E4M) within the first
      four hours; this formulation released 80% of the drug within 12 hours when the
      release was plateaued thereafter. The formulation with 30% Methocel E4M and 70%
      SimpleCap released 100% of the drug within the initial 12 hours and exhibited a
      Zero Order slow-release kinetic pattern. In general, the release kinetic rate of
      the formulations containing Methocel K100M appeared to be slower than Methocel
      E4M. This alteration may be due to a higher molecular weight and apparent
      viscosity of Methocel K100M. While most of the formulations were fitted to a slow
      release kinetic pattern, several others including Methocel E4M 100%, 30% Methocel
      E4M+ 70% Simple Cap, 40% Methocel K100M+ 60% SimpleCap, 50% Methocel K100M+ 50%
      SimpleCap, 30% Methocel E4M+ 70% Lactose, 90% Methocel E4M+ 10% Lactose, 40%
      Methocel K100M+ 60% Lactose, and 50% Methocel K100M+ 50% Lactose followed an
      ideal slow-release kinetic pattern of Zero Order or Higuchi. The results of this
      study successfully demonstrated the optiomal composition of slow-release
      compounded capsules of T3. Future studies are warranted to evaluate the in vivo
      performance of the optimal formulations and to establish an in vitro-in vivo
      correlation.

PMID- 29216619
TI  - Stability of Dalteparin 1,000 Unit/mL in 0.9% Sodium Chloride for Injection in
      Polypropylene Syringes.
AB  - The stability of dalteparin 1,000 units/mL in 0.9% sodium chloride for injection
      stored in polypropylene syringes under refrigeration was examined. Dalteparin
      1,000-units/mL syringes were prepared by adding 9 mL of 0.9% sodium chloride for
      injection to 1 mL of dalteparin sodium 10,000 unit/mL from commercial single-use
      syringes. Compounded solutions in 0.5-mL aliquots were transferred to 1-mL
      polypropylene syringes and sealed with a Luer lock tip cap and stored at
      refrigerated temperatures (2 degrees C to 8 degrees C) with ambient fluorescent
      light exposure. Syringes from three batches of dalteparin 1,000 units/mL were
      potency tested in duplicate by a stability-indicating high-performance liquid
      chromatography assay using a 0.5-mL sample at specified intervals. Visual and pH
      testing were performed on each batch. Samples were visually inspected for
      container integrity, color, and clarity. Samples for pH testing were prepared
      using a 1:1 dilution of dalteparin 1,000 units/mL in sterile water for injection
      and underwent duplicate analysis at each time point. High-performance liquid
      chromatography analyses showed a remaining percent of the initial dalteparin
      content at day 30 of 94.88% +/- 2.11%. Samples remained colorless and clear with
      no signs of container compromise and no visual particulate matter at each time
      point. Throughout the 30-day study period, pH values remained within 0.3-pH units
      from the initial value of 5.84. Dalteparin 1,000 unit/mL in 0.9% sodium chloride
      for injection, packaged in 1-mL polypropylene syringes was stable for at least 30
      days while stored at refrigerated conditions with ambient fluorescent light
      exposure.

PMID- 29216620
TI  - Physicochemical Stability of an Oral Suspension of Trimethoprim 20 mg/mL in
      Combination with Sulfadiazine 200 mg/mL in PCCA Base SuspendIt.
AB  - Trimethoprim is a diaminopyrimidine antibacterial agent that, like sulfonamides,
      inhibits bacterial folic acid synthesis, but at a different stage in the
      metabolic pathway. It has a similar spectrum of activity to the sulfonamides and
      is given by mouth or by injection, either alone or in conjunction with a
      sulfonamide, such as sulfadiazine. Sulfadiazine is a bacteriostatic antibacterial
      agent that interferes with folic acid synthesis in susceptible bacteria. The
      combination of the two drugs produces a synergistic effect against both Gram
      positive and Gram-negative aerobic bacteria, by inhibiting enzymes in the folic
      acid pathways, which in turn inhibits bacterial thymidine synthesis. There are no
      published studies of the stability of the combination of trimethoprim and
      sulfadiazine in a liquid dosage form. An extemporaneously compounded suspension
      from pure drug powders or commercial tablets would provide an alternative option
      to meet unique patient needs. The purpose of this study was to determine the
      physicochemical stability of trimethoprim combined with sulfadiazine in PCCA base
      SuspendIt. PCCA base SuspendIt is a sugar-free, paraben-free, dye-free, and
      gluten-free thixotropic vehicle containing a natural sweetener obtained from the
      monk fruit. It thickens upon standing to minimize settling of any insoluble drug
      particles and becomes fluid upon shaking to allow convenient pouring during
      administration to the patient. A robust stability-indicating high-performance
      liquid chromatographic assay for the simultaneous determination of trimethoprim
      and sulfadiazine in SuspendIt was developed and validated. This assay was used to
      determine the chemical stability of both drugs in SuspendIt. Samples were
      prepared and stored under three different temperature conditions (5 degrees C, 25
      degrees C, 40 degrees C), and assayed using the high-performance liquid
      chromatographic assay at pre-determined intervals over an extended period of time
      as follows: 0, 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated
      temperature. Physical data such as pH, viscosity, appearance, and average
      particle size were also monitored. The study showed that drug concentration did
      not go below 90% of the label claim (initial drug concentration) at room
      temperature and in the refrigerator. The pH values also did not change
      significantly. There was some variability in viscosity and average particle size.
      This study demonstrates that trimethoprim and sulfadiazine are physically and
      chemically stable in combination in SuspendIt for 182 days at room temperature
      and in the refrigerator, thus providing a viable, compounded alternative for both
      drugs in a liquid dosage form, with an extended beyond-use-date to meet patient
      needs.

PMID- 29216621
TI  - Stability of Dexmedetomidine in 0.9% Sodium Chloride in Two Types of Intravenous
      Infusion Bags.
AB  - Dexmedetomidine is a frequently used sedative in the critical care setting. It is
      commercially available as a 4-mg/mL premixed compound or as 200-mcg/2-mL vials
      that must be further diluted prior to administration. However, limited data exist
      regarding the stability of dexmedetomidine admixtures compounded from the 200
      mcg/2-mL vials, particularly for durations greater than 48 hours. Therefore, we
      performed stability testing on compounded dexmedetomidine prepared in two types
      of intravenous infusion bags for 14 days. Dexmedetomidine is available as 200
      mcg/2-mL vials for dilution, 80-mcg/20-mL single-dose vials, and as 200-mcg/50-mL
      and 400-mcg/100-mL glass bottles. The stability of dexmedetomidine admixtures has
      previously been tested for 48 hours. The purpose of this analysis was to test the
      stability of dexmedetomidine admixtures for 14 days. Six dexmedetomidine
      admixtures of 200 mcg/50 mL were compounded in polyvinyl chloride and non
      polyvinyl chloride bags, three of which were stored under refrigeration and three
      of which were kept at room temperature. High-performance liquid chromatography
      testing was performed to determine the concentration at Days 1 through 14.
      Stability was determined by taking the mean concentration of samples taken from
      each bag. All samples were tested in duplicate. A sample was considered stable if
      the concentration was greater than 90% of the original concentration. All samples
      retained over 90% of the drug under their respective storage conditions for the
      duration of the study. At time 0, the concentration of dexmedetomidine was
      between 3.99 mcg/mL and 4.01 mcg/mL. On Day 14, the mean concentration was
      between 95.8% and 98.9%, depending on the bag type and storage condition. The pH
      remained between 4.7 and 5.8 during the study period as has previously been
      reported in the literature. Dexmedetomidine admixtures of 200 mcg/50 mL were
      stable in both polyvinyl chloride bags and non-polyvinyl chloride bags for 14
      days under refrigeration and 48 hours at room temperature. This represents the
      longest time allowable under United States Pharmacopeia Chapter <797> without the
      need for sterility testing.

PMID- 29216623
TI  - Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug
      Resistance by Targeting CCNG2 in Breast Cancer.
AB  - BACKGROUND/AIMS: Treatment of breast cancer remains a clinical challenge. This
      study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for
      breast cancer and understand the underlying mechanism in breast cancer
      progression. METHODS: The expression levels of endogenous and exosomal miRNAs
      were examined by real time PCR, and the expression level of the target protein
      was detected by western blot. Scanning electron and confocal microscopy were used
      to characterize exosomes and to study their uptake and transfer. Luciferase
      reporter plasmids and its mutant were used to confirm direct targeting.
      Furthermore, the functional significance of exosomal miR-1246 was estimated by
      invasion assay and cell viability assay. RESULTS: In this study, we demonstrate
      that exosomes carrying microRNA can be transferred among different cell lines
      through direct uptake. miR-1246 is highly expressed in metastatic breast cancer
      MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant
      breast cells. Moreover, miR-1246 can suppress the expression level of its target
      gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally,
      treatment with exosomes derived from MDA-MB-231 cells could enhance the
      viability, migration and chemotherapy resistance of non-malignant HMLE cells.
      CONCLUSIONS: Together, our results support an important role of exosomes and
      exosomal miRNAs in regulating breast tumor progression, which highlights their
      potential for applications in miRNA-based therapeutics.

PMID- 29216625
TI  - Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter
      the Arena.
AB  - Cancer metastasis occurs through a series of sequential steps, which involves
      dissemination of tumor cells from a primary site and colonization in distant
      tissues. To promote the invasion-metastasis cascade, carcinoma cells usually
      initiate a cell-biological program called epithelial-mesenchymal transition
      (EMT), which is orchestrated by a set of master regulators, including TGF-beta,
      Snail, ZEB and Twist families. The biological activities of these molecules are
      tightly regulated by a variety of cell-intrinsic pathways as well as
      extracellular cues. Recently, accumulating evidence indicates that long non
      coding RNAs (lncRNAs) represent some of the most differentially expressed
      transcripts between primary and metastatic cancers. LncRNAs including MALAT1,
      HOTAIR, H19, LncRNA-ATB, and LincRNA-ROR have been reported to be involved in the
      process of EMT, mainly through cross-talking with master regulators of EMT. Thus,
      understanding the different and precise molecular mechanisms by which functional
      lncRNAs switch EMT on and off is important for opening up new avenues in lncRNA
      directed diagnosis, prognosis, and therapeutic intervention against cancer.

PMID- 29216626
TI  - Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization.
AB  - BACKGROUND/AIMS: Hmgn2 is involved in regulating embryonic development, but its
      physiological function during embryo implantation and decidualization remains
      unknown. METHODS: In situ hybridization, real-time PCR, RNA interference, gene
      overexpression and MTS assay were used to examine the expression of Hmgn2 in
      mouse uterus during the pre-implantation period and explore its function and
      regulatory mechanisms in epithelial adhesion junction and stromal cell
      proliferation and differentiation. RESULTS: Hmgn2 was primarily accumulated in
      uterine luminal epithelia on day 4 of pregnancy and subluminal stromal cells
      around the implanting blastocyst at implantation sites on day 5. Similar results
      were observed during delayed implantation and activation. Meanwhile, Hmgn2
      expression was visualized in the decidua. In uterine epithelial cells, silencing
      of Hmgn2 by specific siRNA reduced the expression of adhesion molecules Cdh1,
      Cdh2 and Ctnnb1 and enhanced the expression of Muc1, whereas constitutive
      activation of Hmgn2 exhibited the opposite effects, suggesting a role for Hmgn2
      in attachment reaction during embryo implantation. Estrogen stimulated the
      expression of Hmgn2 in uterine epithelia, but the stimulation was abrogated by ER
      antagonist ICI 182,780. Further analysis evidenced that attenuation of Hmgn2
      might eliminate the regulation of estrogen on the expression of Cdh1, Cdh2 and
      Ctnnb1. In uterine stromal cells, progesterone induced the accumulation of Hmgn2
      which advanced the expression of Prl8a2 and Prl3c1, two well-known
      differentiation markers for decidualization, but did not affect the proliferation
      of stromal cells. Knockdown of Hmgn2 blocked the progesterone-induced
      differentiation of uterine stromal cells. Moreover, Hmgn2 might serve as an
      intermediate to mediate the regulation of progesterone on Hand2. CONCLUSION:
      Hmgn2 may play an important role during embryo implantation and decidualization.

PMID- 29216627
TI  - A Simplified Approach to Extravascular Lung Water Assessment Using Point-of-Care
      Ultrasound in Patients with End-Stage Chronic Renal Failure Undergoing
      Hemodialysis.
AB  - BACKGROUND: Fluid overload leading to pulmonary congestion is an important issue
      in patients undergoing hemodialysis. This study aimed to determine if a
      simplified method of extravascular lung water assessment using ultrasound
      provided clinically relevant information. METHODS: This prospective study
      recruited 47 patients from a single hemodialysis center. Pulmonary ultrasound was
      performed before and after 2 hemodialysis sessions in 28 regions on the thorax.
      The B-line score was defined as the percentage regions where B-lines were
      present. RESULTS: When B-lines were detected before hemodialysis, a significant
      relationship was found between fluid removal and the change in B-line score.
      Patients with a B-line score of >=21.4% (4th quartile) after the second
      hemodialysis session were more likely to be hospitalized for pulmonary edema or
      acute coronary syndrome. CONCLUSIONS: A simplified pulmonary assessment using
      ultrasound provides relevant information about pulmonary congestion in
      hemodialysis patients and identifies patients at risk of hospitalization for
      heart-related problems.

PMID- 29216624
TI  - Sildenafil (Viagra(r)) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular
      Hypercontractility in ApoE-/- Mice.
AB  - BACKGROUND/AIMS: The atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse
      exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The
      objectives of this study were: a) to determine the relative contribution of
      cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1)
      to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b)
      to investigate the beneficial effects of the phosphodiesterase 5 inhibitor
      sildenafil on this endothelial dysfunction. METHODS: Adult male apoE-/- mice were
      treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated
      ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular
      contractile response to phenylephrine (PE) in aortic rings were evaluated before
      and after incubation with Cox-1 (SC-560) or Cox-2 (NS-398) inhibitors or the TP
      antagonist SQ-29548, and on contractile responsiveness to ET-1. RESULTS: ApoE-/-
      mice exhibited enhanced vasoconstriction to PE (Rmax ~35%, p<0.01), which was
      prevented by treatment with sildenafil. The enhanced PE-induced contractions were
      abolished by both Cox-1 inhibition and TP antagonist, but were not modified by
      Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced
      contractions to ET-1 (Rmax ~30%, p<0.01), which were attenuated in sildenafil
      treated ApoE-/- mice. In addition, we observed augmented levels of vascular
      proinflammatory cytokines in ApoE-/- mice, which were partially corrected by
      treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1). CONCLUSION: The
      present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in
      the mediation of vascular hypercontractility observed in apoE-/-mice. The results
      also show a beneficial effect of sildenafil on this endothelial dysfunction and
      on the proinflammatory cytokines in atherosclerotic animals, opening new
      perspectives for the treatment of other endothelium-related cardiovascular
      abnormalities.

PMID- 29216628
TI  - MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative
      Breast Cancer by Targeting Prrx2.
AB  - BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive
      breast cancer subtype. Our study investigated the functional role of miR-212-5p
      in TNBC. METHODS: Realtime PCR was used to quantify miR-212-5p expression levels
      in 30 paired TNBC samples and adjacent normal tissues. Wound healing and
      Transwell assays were used to evaluate the effects of miR-212-5p expression on
      the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were
      used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p.
      RESULTS: MiR-212-5p was downregulated in TNBC, and its expression levels were
      related to tumor size, lymph node status and vascular invasion in breast cancer.
      We also observed that the miR-212-5p expression level was significantly
      correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p
      induced upregulation of E-cadherin expression and downregulation of vimentin
      expression. The expression of miR212-5p also suppressed the migration and
      invasion capacity of mesenchymal-like cancer cells accompanied by a morphological
      shift towards the epithelial phenotype. Moreover, our study observed that miR-212
      5p overexpression significantly suppressed Prrx2 by targeting its 3'-untranslated
      region (3'-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p
      mediated suppression. CONCLUSIONS: Our study demonstrated that miR-212-5p
      inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby
      inhibiting cell migration and invasion during cancer progression.

PMID- 29216629
TI  - Erratum.

PMID- 29216630
TI  - Rapamycin Promotes the Survival and Adipogenesis of Ischemia-Challenged Adipose
      Derived Stem Cells by Improving Autophagy.
AB  - BACKGROUND/AIMS: Ischemia is one of the main causes of the high rate of
      absorption of transplanted autologous fat. Autophagy allows cells to survive by
      providing energy under starvation. Rapamycin has been found to play a role in
      promoting autophagy. In this study, we investigated whether rapamycin
      participates in the survival and adipogenesis of ischemia-challenged adipose
      derived stem cells (ADSCs) by regulating autophagy. METHODS: Before the cells
      were exposed to oxygen-glucose deprivation (OGD), a simulated ischemic
      microenvironment, the level of autophagy was reduced or increased by lentiviral
      transfection with short hairpin RNA targeting microtubule-associated protein 1
      light chain 3 gene (shRNA-LC3) or treatment with rapamycin, respectively. The
      level of autophagy was assessed by western blotting, transmission electron
      microscopythen the apoptosis ratio was determined through terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and flow
      cytometry. Adipogenesis was further evaluated by oil red O staining and the
      expressions level of some specific proteins for adipocytes. RESULTS: shRNA-LC3
      and rapamycin treatment effectively decreased and improved the level of autophagy
      in cells with or without OGD challenge, respectively. In addition, autophagy
      inhibition increased the apoptosis rate and activated caspase-3 expression level
      in response to OGD, and these were markedly inhibited by rapamycin
      preconditioning. During adipogenesis, autophagy inhibition decreased not only oil
      droplet accumulation but also lipoprotein lipase (LPL) and peroxisome
      proliferator-activated receptor gamma (PPARgamma) expression in cells with or
      without OGD challenge. However, autophagy promotion by rapamycin increased oil
      droplet accumulation and LPL and PPARgamma expression. CONCLUSIONS: Rapamycin may
      promote the survival and adipogenesis of ischemia-challenged ADSCs by
      upregulating autophagy.

PMID- 29216631
TI  - Effect of Cinacalcet Combined with Calcitriol on the Clinical Outcome and Bone
      Metabolism in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism.
AB  - OBJECTIVE: To observe the clinical outcome and the effect of bone metabolism of
      cinacalcet combined with calcitriol in maintenance hemodialysis (MHD) patients
      with severe secondary hyperparathyroidism (SHPT). METHODS: Thirty MHD patients
      with SHPT were enrolled into the study. All patients were given cinacalcet 25-75
      mg and 0.5 MUg calcitriol daily. Serum Ca, P, intact parathyroid hormone (iPTH),
      and bone metabolic markers were measured. The clinical symptoms and their changes
      were investigated. RESULTS: The baseline levels of iPTH, Ca, and P were 1,787.3
      +/- 1,321 pg/mL, 2.54 +/- 0.19 mmol/L, and 2.06 +/- 0.15 mmol/L respectively.
      After 3 months treatment, iPTH decreased by 70%. Serum Ca and P fell to 2.39 +/-
      0.17 and 1.56 +/- 0.50 mmol/L (p < 0.05), respectively. After 6 months, the bone
      specific alkaline phosphatase, osteocalcin, and beta-cross levels were decreased
      by 50, 37, and 49% respectively compared with corresponding values before
      treatment. A decline in the bone density patients was inhibited. CONCLUSION:
      Cinacalcet combined with low dose calcitriol can improve high calcium, high
      phosphorus, and high iPTH in MHD patients with severe SHPT and also improve bone
      metabolism. It can be used as a favorable choice for SHPT treatment.

PMID- 29216632
TI  - Perturbations in Endothelial Dysfunction-Associated Pathways in the Nitrofen
      Induced Congenital Diaphragmatic Hernia Model.
AB  - Although it is well known that nitrofen induces congenital diaphragmatic hernia
      (CDH), including CDH-associated lung hypoplasia and pulmonary hypertension (PH)
      in rodents, the mechanism of pathogenesis remains largely unclear. It has been
      reported that pulmonary artery (PA) endothelial cell (EC) dysfunction contributes
      to the development of PH in CDH. Thus, we hypothesized that there is significant
      alteration of endothelial dysfunction-associated proteins in nitrofen-induced CDH
      PAs. Pregnant SD rats received either nitrofen or olive oil on gestational day
      9.5. The newborn rats were sacrificed and divided into a CDH (n = 81) and a
      control (n = 23) group. After PA isolation, the expression of PA endothelial
      dysfunction-associated proteins was assessed on Western blot and immunostaining.
      We demonstrate that the expression of C-reactive protein and endothelin-1 and its
      receptors, ETA and ETB, were significantly increased in the CDH PAs. Levels of
      phosphorylated myosin light chain were significantly elevated, but those of
      phosphorylated endothelial nitric oxide synthase, caveolin-1, and mechanistic
      target of rapamycin were significantly decreased in the CDH PAs. In this work, we
      elucidate alterations in the expression of endothelial dysfunction-associated
      proteins specific to nitrofen-induced CDH rodent PAs, thereby advancing our
      understanding of the critical role of endothelial dysfunction-associated pathways
      in the pathogenesis of nitrofen-induced CDH.

PMID- 29216633
TI  - Greater Experience of Negative Non-Target Emotions by Patients with
      Neurodegenerative Diseases Is Related to Lower Emotional Well-Being in
      Caregivers.
AB  - BACKGROUND: Behavioral symptoms in patients with neurodegenerative diseases can
      be particularly challenging for caregivers. Previously, we reported that patients
      with frontotemporal dementia (FTD) and Alzheimer's disease (AD) experienced
      emotions that were atypical or incongruent with a given situation (i.e., non
      target emotions). AIM: We tested the hypothesis that greater experience of non
      target emotions by patients is associated with lower caregiver emotional well
      being. METHODS: 178 patients with FTD, AD, or other neurodegenerative diseases
      and 35 healthy individuals watched 3 films designed to induce amusement, sadness,
      and disgust, and then reported their emotions during the films. Caregivers of the
      patients reported their own emotional well-being on the Medical Outcomes Study 36
      item Short-Form Health Survey. RESULTS: In response to the amusement and sadness
      (but not disgust) films, greater experience of non-target emotions by patients
      was related to lower caregiver emotional well-being. These effects were specific
      to patients' experience of negative non-target emotions (i.e., not found for
      positive non-target emotions or for negative or positive target emotions).
      CONCLUSION: The findings reveal a previously unstudied patient behavior that is
      related to worse caregiver emotional well-being. Future research and clinical
      assessment may benefit from evaluating non-target emotions in patients.

PMID- 29216634
TI  - Lysine Restriction Affects Feed Intake and Amino Acid Metabolism via Gut
      Microbiome in Piglets.
AB  - BACKGROUND/AIMS: Our previous reports suggested that dietary supplementation with
      lysine influenced intestinal absorption and metabolism of amino acids. In this
      study, we further investigated the effect of lysine restriction (30%) on feed
      intake and we also tested the hypothesis that gut microbiome contributed to the
      potential mechanism of lysine restriction-mediated feeding behavior. Here, we
      profiled gut microbial communities by sequencing 16S ribosomal ribonucleic acid
      (rRNA) genes from gut samples as well as growth performance, serum hormones, and
      intestinal lysine transport in a piglet model. RESULTS: Piglets preferred to the
      lysine restricted diet when giving three diets and the feed intake was markedly
      higher in the lysine-restricted group than that in the control group. Altered
      hormones (leptin, CCK, and ghrelin) might contribute to the feeding behavior
      caused by lysine restriction. Meanwhile, lysine transporting ability (SLC7A1 and
      SLC7A2 expression, intestinal electrophysiological changes, and amino acid pool
      in mesenteric vein) was decreased in response to lysine restriction. Through deep
      sequencing of bacterial rRNA markers, we observed that bacterial diversity was
      enhanced in the lysine-restricted group (Shannon H, PD, and Chao1). At the phylum
      level, lysine restriction enhanced gut Actinobacteria, Saccharibacteria, and
      Synergistetes abundances. At the family level, Moraxellaceae, Halomonadaceae,
      Shewanellaceae, Corynebacteriaceae, Bacillaceae, Comamonadaceae,
      Microbacteriaceae, Caulobacteraceae, and Synergistaceae abundances were increased
      in response to lysine restriction. Predictive functional profiling of microbial
      communities by PICRUSt also confirmed that dietary lysine restriction affected
      gut microbiome, which might further mediate amino acid metabolism, membrane
      transport, and endocrine system. CONCLUSION: Our results indicated that lysine
      restriction inhibited intestinal lysine transport and promoted feed intake, which
      might be associated with gut microbiome.

PMID- 29216635
TI  - Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain
      White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging
      Study.
AB  - Neuropsychiatric disorders that frequently initially emerge during adolescence
      are associated with deficits in the omega-3 (n-3) fatty acid docosahexaenoic acid
      (DHA), elevated proinflammatory signaling, and regional reductions in white
      matter integrity (WMI). This study determined the effects of altering brain DHA
      accrual during adolescence on WMI in the rat brain by diffusion tensor imaging
      (DTI), and investigated the potential mediating role of proinflammatory
      signaling. During periadolescent development, male rats were fed a diet deficient
      in n-3 fatty acids (DEF, n = 20), a fish oil-fortified diet containing preformed
      DHA (FO, n = 20), or a control diet (CON, n = 20). In adulthood, DTI scans were
      performed and brain WMI was determined using voxelwise tract-based spatial
      statistics (TBSS). Postmortem fatty acid composition, peripheral (plasma IL
      1beta, IL-6, and C-reactive protein [CRP]) and central (IL-1beta and CD11b mRNA)
      proinflammatory markers, and myelin basic protein (MBP) mRNA expression were
      determined. Compared with CON rats, forebrain DHA levels were lower in DEF rats
      and higher in FO rats. Compared with CON rats, DEF rats exhibited greater radial
      diffusivity (RD) and mean diffusivity in the right external capsule, and greater
      axial diffusivity in the corpus callosum genu and left external capsule. DEF rats
      also exhibited greater RD than FO rats in the right external capsule. Forebrain
      MBP expression did not differ between groups. Compared with CON rats, central (IL
      1beta and CD11b) and peripheral (IL-1beta and IL-6) proinflammatory markers were
      not different in DEF rats, and DEF rats exhibited lower CRP levels. These
      findings demonstrate that deficits in adolescent DHA accrual negatively impact
      forebrain WMI, independently of elevated proinflammatory signaling.

PMID- 29216637
TI  - ILUVIEN in Diabetic Macular Edema: The Choice of Second-Line Corticosteroid
      Should Be Left to the Clinical Judgement of the Treating Physician.

PMID- 29216636
TI  - Reduction of Uterine Perfusion Pressure Induced Redistribution of Endothelin
      Receptor Type-B Between the Intima and Media Contributes to the Pathogenesis of
      Pregnancy-Induced Hypertension.
AB  - BACKGROUND/AIMS: Studies have shown that a change in endothelin receptor
      expression in the artery is related to pregnancy-induced hypertension (PIH).
      However, the mechanism underlying this change remains unclear. METHODS: To test
      whether the distribution of endothelin receptor type-A (ETAR) and type-B (ETBR)
      plays an important role in PIH, a reduction of uterine perfusion pressure (RUPP)
      rat model was used to mimic some of the features of PIH; the resulting variable
      endothelin receptor expression was investigated in the media and intima of the
      aorta. Single vascular smooth muscle cells (VSMCs) were isolated from RUPP and
      normal pregnant (NP) rats to study the effect of ETAR and ETBR in smooth muscle
      cells. RESULTS: Compared with NP rats, RUPP rats had a significant redistribution
      of ETBR expression in the intima and media, while there was no significant
      difference in ETAR expression between the two groups. ETBR upregulation in VSMCs
      enhanced cellular contraction and contributed to PIH. The TNF-alpha plasma levels
      in RUPP rats were two-fold higher than those of NP rats, which upregulated the
      expression of ETBR in VSMCS through the NF-kappaB pathways in RUPP rats.
      CONCLUSION: Redistribution of ETBR between the media and intima played an
      important role in the pathogenesis of PIH.

PMID- 29216638
TI  - MicroRNA-122 Inhibits Lipid Droplet Formation and Hepatic Triglyceride
      Accumulation via Yin Yang 1.
AB  - BACKGROUND/AIMS: An increase in intracellular lipid droplet formation and hepatic
      triglyceride (TG) content usually results in nonalcoholic fatty liver disease.
      However, the mechanisms underlying the regulation of hepatic TG homeostasis
      remain unclear. METHODS: Oil red O staining and TG measurement were performed to
      determine the lipid content. miRNA expression was evaluated by quantitative PCR.
      A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1)
      by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its
      mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR
      SHP) pathway were evaluated by quantitative PCR and Western blot analyses.
      RESULTS: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic
      hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic
      steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics
      before FFA induction inhibited lipid droplet formation and TG accumulation in
      vitro. These results were verified by overexpressing miR-122 in the livers of STZ
      HFD-induced NASH mice. The 3'-untranslated region (3'UTR) of YY1 mRNA is
      predicted to contain an evolutionarily conserved miR-122 binding site. In silico
      searches, a luciferase reporter assay and quantitative PCR analysis confirmed
      that miR-122 directly bound to the YY1 3'UTR to negatively regulate YY1 mRNA in
      HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1,
      may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1
      FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122
      overexpression. This finding was also confirmed by overexpression of miR-122 in
      the livers of NASH mice. CONCLUSIONS: The present results indicate that miR-122
      plays an important role in lipid (particularly TG) accumulation in the liver by
      reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

PMID- 29216639
TI  - Exendin-4 Induces Bone Marrow Stromal Cells Migration Through Bone Marrow-Derived
      Macrophages Polarization via PKA-STAT3 Signaling Pathway.
AB  - BACKGROUND/AIMS: The synthesis and degradation processes involved in bone
      remodeling are critically regulated by osteoblasts and osteoclasts. The GLP-1
      receptor agonist Exendin-4 is beneficial for osteoblast differentiation and
      increases the number of osteoblasts. METHODS: We constructed an ovariectomized
      model to evaluate the impact of Exendin-4 on bone formation in osteoporosis. A
      macrophage-depleted model was also created to investigate the effect of
      macrophages on bone formation. Thirty-two female WT C57BL/6 mice (aged 3 months)
      were randomly assigned to a normal control group and four ovariectomized (OVX)
      subgroups: OVX + vehicle group, OVX + Exendin-4 (4.2 ug/kg/day) group, OVX +
      chloride phosphate liposome group and OVX + chloride phosphate liposome + Exendin
      4 group. RESULTS: In this study, we found that Exendin-4 not only increased the
      number of osteoblasts and decreased the number of osteoclasts, but also increased
      the number of bone marrow stromal cells (BMSCs) at the bone surface. Moreover, we
      found that OVX mice treated with Exendin-4 increased TGF-beta1 levels at the bone
      surface compared with that in OVX mice. Besides, Exendin-4 promoted the
      polarization of bone marrow-derived macrophages into M2 subtype and increased TGF
      beta1 secretion by the M2 subtype. Finally, we found that Exendin-4 induced
      macrophage polarization via the cAMP-PKA-STAT3 signaling pathway. CONCLUSION:
      Exendin-4 promotes bone marrow-derived macrophage polarization to the M2 subtype
      and induces BMSC migration to the bone surface via PKA-STAT3 signaling.

PMID- 29216640
TI  - Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1alpha and VEGF
      Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells.
AB  - BACKGROUND/AIMS: The goal of this study was to detect the expression of hypoxia
      inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor
      (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib,
      a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic
      conditions and to explore the signaling mechanism involved in regulating the
      hypoxia-induced expression of HIF-1alpha and VEGF in RPE cells. METHODS: D407
      cells were cultured in normoxic or hypoxic conditions, with or without celecoxib
      or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was
      assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed
      to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1alpha, VEGF and
      COX-2. RESULTS: Celecoxib inhibited the proliferation of RPE cells in a dose
      dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA
      and protein levels and decreased HIF-1alpha protein expression. HIF-1alpha
      activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down
      regulation of HIF-1alpha and VEGF required the suppression of the hypoxia-induced
      PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells
      treated with celecoxib. CONCLUSIONS: The antiangiogenic effects of celecoxib in
      RPE cells under hypoxic conditions resulted from the inhibition of HIF-1alpha and
      VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT
      dependent pathway.

PMID- 29216641
TI  - ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell
      Carcinoma.
AB  - OBJECTIVE: ZNF750, a transcriptional regulator of epidermal differentiation, has
      been identified as a tumor suppressor in esophageal squamous cell carcinoma
      (ESCC). The aim of the present study was to investigate the clinical and
      prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750
      knockdown on cell proliferation, migration, and invasion in ESCC. METHODS: A
      total of 124 patients with ESCC who underwent curative esophagectomy were
      evaluated in this study. The expression of ZNF750 in surgical specimens was
      immunohistochemically assessed and used in the analysis of clinicopathological
      features and overall survival (OS). The molecular role of ZNF750 was investigated
      by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines.
      RESULTS: Low ZNF750 expression had a significant correlation with positive lymph
      node metastasis (p = 0.028). Furthermore, there was a significant relationship
      between low expression of ZNF750 in ESCC and a poor OS, and a multivariate
      analysis showed that low ZNF750 expression was an independent prognostic factor
      (p = 0.020). The cell growth, migration, and invasion were significantly
      increased by downregulation of ZNF750. CONCLUSIONS: The low expression of ZNF750
      was significantly associated with a poor prognosis, and ZNF750 expression may,
      therefore, be a reliable prognostic biomarker in ESCC.

PMID- 29216642
TI  - Taurine Protects Mouse Spermatocytes from Ionizing Radiation-Induced Damage
      Through Activation of Nrf2/HO-1 Signaling.
AB  - BACKGROUND/AIMS: The increasing prevalence of ionizing radiation exposure has
      inevitably raised public concern over the potential detrimental effects of
      ionizing radiation on male reproductive system function. The detection of drug
      candidates to prevent reproductive system from damage caused by ionizing
      radiation is urgent. We aimed to investigate the protective role of taurine on
      the injury of mouse spermatocyte-derived cells (GC-2) subjected to ionizing
      radiation. METHODS: mouse spermatocytes (GC-2 cells) were exposed to ionizing
      radiation with or without treatment of Taurine. The effect of ionizing radiation
      and Taurine treatment on GC-2 cells were evaluated by cell viability assay
      (CCK8), cell cycle and apoptosis. The relative protein abundance change was
      determined by Western blotting. The siRNA was used to explore whether Nrf2
      signaling was involved in the cytoprotection of Taurine. RESULTS: Taurine
      significantly inhibited the decrease of cell viability, percentage of apoptotic
      cells and cell cycle arrest induced by ionizing radiation. Western blot analysis
      showed that taurine significantly limited the ionizing radiation-induced down
      regulation of CyclinB1 and CDK1, and suppressed activation of Fas/FasL system
      pathway. In addition, taurine treatment significantly increased the expression of
      Nrf2 and HO-1 in GC-2 cells exposed to ionizing radiation, two components in
      antioxidant pathway. The above cytoprotection of Taurine was blocked by siNrf2.
      CONCLUSION: Our results demonstrate that taurine has the potential to effectively
      protect GC-2 cells from ionizing radiation- triggered damage via upregulation of
      Nrf2/HO-1 signaling.

PMID- 29216644
TI  - Prognostic Factors and Efficacy for Continuous Renal Replacement Therapy in
      Critically Ill Patients: A Chinese Single-Center Retrospective Study.
AB  - BACKGROUND: There is controversy about the efficacy and prognostic factors for
      continuous renal replacement therapy (CRRT) in China due to practice variation.
      Our aim is to investigate these questions. METHOD: A total of 613 adult patients
      receiving CRRT in last 3 years from one Chinese ICU were enrolled. The analysis
      of demographic data, vital signs, and laboratory tests prior to CRRT and outcomes
      were performed. The data between pre- and post-CRRT were compared for efficacy
      analysis. RESULTS: Prior to CRRT, partial pressure of carbon dioxide (PCO2),
      systolic blood pressure (SBP), gender, age, bilirubin, cystatin C, and mechanical
      ventilation were correlated with in-hospital mortality. In a binary logistic
      regression, PCO2, SBP, age, and gender were significant in predicting mortality.
      Cox regression analysis demonstrated PCO2 independent association with mortality,
      and lower SBP worse mortality. CRRT could eliminate the fluid and metabolites.
      CONCLUSION: CO2 retention and low SBP prior to CRRT were associated with
      increased mortality. CRRT significantly improved hemeostasis.

PMID- 29216643
TI  - Emerging Treatment Options in Atopic Dermatitis: Topical Therapies.
AB  - Atopic dermatitis is a chronic inflammatory skin disorder affecting children and
      adults, with the majority presenting mild to moderate disease severity. The use
      of topical corticosteroids (TCSs) in combination with emollients has been the
      mainstay for treating mild to moderate atopic dermatitis since the 1950s, and as
      a supplement to systemic treatment in severe disease. However, while very
      effective, TCSs are often accompanied by poor adherence due to corticophobia
      (fear of using corticosteroids in patients or doctors), unwanted side effects,
      and in some cases insufficient clinical response. Topical calcineurin inhibitors
      (TCIs) are able to inhibit the activation of T-lymphocytes and thereby diminish
      inflammation. In some patients the use of TCIs has been limited due to a
      localized burning sensation on the first days of treatment, and also due to fear
      of other adverse effects. Consequently, there has been a need for the development
      of new topical products for atopic dermatitis. Novel topical therapies are in the
      pipeline and comprise both new doses and formulations of well-known
      pharmaceutical molecules and novel approaches targeting unique inflammatory
      pathways and mechanisms of disease, with a promise of higher efficacy and less
      harmful side effects. We review topical drugs in the pipeline for atopic
      dermatitis, and focus on those available in the clinicaltrials.gov database with
      a first received date from January 1, 2014 to May 31, 2017.

PMID- 29216650
TI  - [Have Multimodal and Perioperative Therapeutic Strategies Changed the Survival
      after Oncological Oesophageal Surgery in the Last Two Decades? A Retrospective
      Cohort Analysis over 23 Years].
AB  - BACKGROUND: Esophageal malignoma is among the most frequent causes for cancer
      related deaths. The only definite curative therapy is esophagectomy embedded in
      various multimodal treatment regimens. The aim of this study was to evaluate long
      term development after esophageal surgery in the last two decades in order to
      observe possible trends and their influence on short, medium and long term
      survival. PATIENTS AND METHODS: Cases of 301 patients who underwent esophagectomy
      between 1989 and 2012 were analysed retrospectively. To investigate possible
      changes in perioperative management and their influence on prognosis patients
      were divided into two cohorts (A: surgery between 1989 and 2000; B: surgery
      between 2001 and 2012) and further analyzed with regard to demographics, tumor
      entity, stage, complications and survival. Statistics were conducted to compare
      both groups while p <= 0.05 was regarded as statistically significant. RESULTS:
      In cohort B patients were significantly older compared to cohort A and underwent
      surgery in earlier tumor stages with a higher lymphnode yield. Also an increased
      incidence of adenocarcinoma was observed. While overall morbidity did not change
      significantly, a decreased rate of anastomotic leakage was observed in cohort B
      (5.5%) compared to cohort A (12.3%) accompanied by a simultaneous increase in
      cardiac events (A: 3.6% vs. B: 12.3%). Overall 30-days-mortality was 2.7% and
      decreased significantly from 5% in cohort A to 0.7% in cohort B (p = 0.05).
      Median survival was 46 +/- 7 month in cohort A, in cohort B an increase could be
      observed (53 +/- 7 months, p = 0.03). By univariate analysis we could demonstrate
      that stage, affected lymph nodes, lymphnode ratio (LNR) and incidence of
      postoperative complications were significant predictors for the survival whereas
      in multivariate analysis T-stage, R-status and LNR were independent predictors
      for patients outcome. CONCLUSION: Patients undergoing esophageal resection for
      cancer nowadays are older than in the past decades. Earlier cancer diagnosis,
      more radical surgical techniques with an extended lymphnode dissection, a
      decrease in anastomotic leakage and an improved perioperative care seem to
      compensate for this potential demographic disadvantage. The most important
      independent predictor of outcome after esophageal resection is the LNR.

PMID- 29216651
TI  - Regenerative Medicine/Cardiac Cell Therapy: Pluripotent Stem Cells.
AB  - For more than 20 years, tremendous efforts have been made to develop cell-based
      therapies for treatment of heart failure. However, the results of clinical trials
      using somatic, nonpluripotent stem or progenitor cells have been largely
      disappointing in both cardiology and cardiac surgery scenarios. Surgical groups
      were among the pioneers of experimental and clinical myocyte transplantation
      ("cellular cardiomyoplasty"), but little translational progress was made prior to
      the development of cellular reprogramming for creation of induced pluripotent
      stem cells (iPSC). Ever since, protocols have been developed which allow for the
      derivation of large numbers of autologous cardiomyocytes (CMs) from patient
      specific iPSC, moving translational research closer toward clinical pilot trials.
      However, compared with somatic cell therapy, the technology required for safe and
      efficacious pluripotent stem cell (PSC)-based therapies is extremely complex and
      requires tremendous resources and close interactions between basic scientists and
      clinicians. This review summarizes PSC sources, strategies to derive CMs, current
      cardiac tissue engineering approaches, concerns regarding immunogenicity and
      cellular maturity, and highlights the contributions made by surgical groups.

PMID- 29216652
TI  - ?

PMID- 29216653
TI  - ?

PMID- 29216654
TI  - ?

PMID- 29216655
TI  - ?

PMID- 29216656
TI  - ?

PMID- 29216657
TI  - ?

PMID- 29216658
TI  - ?

PMID- 29216659
TI  - ?

PMID- 29216660
TI  - ?

PMID- 29216661
TI  - ?

PMID- 29216662
TI  - ?

PMID- 29216663
TI  - [Reconstructive surgery of ureteral stricture disease].

PMID- 29216665
TI  - ?

PMID- 29216664
TI  - [Acute scrotal pain in childhood: legal pitfalls].
AB  - Acute scrotal pain in childhood is an emergency.Sudden scrotal pain may be caused
      by a variety of diseases. Therefore, it is important to carefully consider the
      specific medical history and possible differential diagnoses in each case for
      fast and decisive action (e. g. in case of testicular torsion). As minors lack
      the capacity for consent, it is absolutely necessary to obtain consent from their
      legal guardian. However, obtaining consent in the available time frame can cause
      organisational challenges in an acute emergency, which may lead to situations in
      the daily routine where a therapeutic decision needs to be taken (including
      surgery) without legal security based on consent by the guardian. In some cases,
      the child's consent also needs to be taken into account, depending on its age and
      development.For the physician and surgeon in charge, the legal evaluation of the
      case at hand and therewith the obtainment of legal security are of great
      significance.

PMID- 29216666
TI  - [Cardiac Rehabilitation].
AB  - Physical training, psychosocial intervention, nutrition counselling and
      optimisation of secondary preventive medication to reduce morbidity and mortality
      of the disease as well as the reintegration into social life and return to work
      are equivalent goals of cardiac rehabilitation. This requires multifactorial
      intervention by a multidisciplinary team. In Germany, cardiac rehabilitation
      starting early after an index event could demonstrate a significant reduction of
      total mortality, myocardial infarction and hospitalisation during a follow-up of
      1-2 years in 5 controlled cohort studies including 12 556 patients after
      myocardial infarction and CABG surgery. The reduction of clinical events was
      obtained in addition to rapid revascularisation therapy during the acute coronary
      event and on top of evidence based medication. In national and international
      guidelines, cardiac rehabilitation is recommended as well after valve surgery or
      intervention, in patients with heart failure and after ICD-, CRT- and VAD
      implantation. Cardiac rehabilitation in Germany should be evaluated in a
      randomised controlled trial as well. In addition, multifactorial interventions
      should be tailored individually to specific patient subgroups, medical conditions
      and comorbidities. Return to work should be emphasized as a major topic of
      cardiac rehabilitation.

PMID- 29216667
TI  - [Confounding and Biasing Variables in Observational and Intervention Studies in
      Rehabilitation].
AB  - To prove and determine effects of rehabilitation treatments, appropriate study
      designs have to be applied which allow inferring that differences in the outcome
      variables (e .g. health state) are causally determined by rehabilitation
      treatments. In observational studies confounding variables may affect or distort
      the association between treatment and outcome variables. Preference for a
      treatment, motivation for treatment or level of impairment before rehabilitation
      are typical confounders in rehabilitational intervention studies. These potential
      confounders are especially important if patients chose treatment voluntarily or
      the treatment has been suggested because of specific impairment characteristics
      (external program effects). Appropriately controlled intervention studies
      (especially randomized control trials, RCTs) allow controlling for such biasing
      effects. But also for appropriate controlled intervention studies, biasing
      effects may arise due to the implementation of the study design (e. g. selection
      of participants, applying assessment instruments, communication of participants
      of different study groups; design effects, treatment contaminations) and may
      deteriorate the unambiguous interpretability of empirical results. It is shown
      which confounding and distortional effects have to be regarded that may affect
      the interpretability of associations. Recommendations for planning, conducting
      and analyzing empirical studies are given to avoid such biasing effects in the
      best possible way.

PMID- 29216668
TI  - Characteristic Chromatogram: A Method of Discriminate and Quantitative Analysis
      for Quality Evaluation of Uncaria Stem with Hooks.
AB  - It remains a challenge to establish new monographs for herbal drugs derived from
      multiple botanical sources. Specifically, the difficulty involves discriminating
      and quantifying these herbs with components whose levels vary markedly among
      different samples. Using Uncaria stem with hooks as an example, a characteristic
      chromatogram was proposed to discriminate its five botanical origins and to
      quantify its characteristic components in the chromatogram. The characteristic
      chromatogram with respect to the components of Uncaria stem with hooks with the
      five botanical origins was established using 0.02% diethylamine and acetonitrile
      as the mobile phase. The total analysis time was 50 min and the detection
      wavelength was 245 nm. Using the same chromatogram parameters, the single
      standard to determine multicomponents method was validated to simultaneously
      quantify nine indole alkaloids, including vincosamide, 3alpha-dihydrocadambine,
      isocorynoxeine, corynoxeine, isorhynchophylline, rhynchophylline, hirsuteine,
      hirsutine, and geissoschizine methyl ether. The results showed that only the
      Uncaria stem with hooks from Uncaria rhynchophylla, the most widely used in the
      herbal market, showed the presence of these nine alkaloids. The conversion
      factors were 1.27, 2.32, 0.98, 1.04, 1.00, 1.02, 1.26, 1.33, and 1.25,
      respectively. The limits of quantitation were lower than 700 ng/mL. The total
      contents of 31 batches of Uncaria stem with hooks were in the range of 0.1 -
      0.6%, except for Uncaria hirsuta Havil and Uncaria sinensis (Oliv.) Havil. The
      results also showed that the total content of indole alkaloids tended to decrease
      with an increase in the hook diameter. This showed that the characteristic
      chromatogram is practical for controlling the quality of traditional Chinese
      medicines with multiple botanical origins.

PMID- 29216669
TI  - ["It Is Up To You": A Qualitative Study of Inequalities In Healthcare From The
      Patient's Perspective].
AB  - Objective The aim of this qualitative study was to explore inequalities in
      healthcare from the patient's perspective. Methods 44 semi-structured interviews
      with patients, aged 59-80 years, were conducted at the university hospital in
      Halle, Germany in 2014 and 2015. We analyzed the narratives following inductive
      qualitative content analysis. Results Most of the patients (82%) perceived
      inequalities in healthcare. Dimensions of healthcare inequalities from the
      patient's perspective were regional differences, type of health insurance,
      quality of physicians and the patients themselves (Income, Age). The patient's
      engagement in utilization was mentioned most often as a dimension of
      inequalities, but not considered a disadvantage. From the patient's perspective,
      inequalities were more prevalent in the outpatient sector (waiting time, lack of
      time). Economization in the healthcare system was viewed as the main reason of
      healthcare inequalities. We found no differences between patients of high and low
      socioeconomic status. Conclusion From the patient's point of view, their own
      capacity to orient and engage themselves in the healthcare system, as well as
      reduction of barriers to accessing outpatient care are highly important for
      reducing inequalities in healthcare.

PMID- 29216670
TI  - [Systematic Review of the Burden of Campylobacter-associated Disease].
AB  - Bacteria of the genus Campylobacter spp. are one of the most common causes of
      gastroenteritis and can lead to serious sequelae. Several studies have estimated
      the disease burden of Campylobacter spp. with the quantitative metric of
      disability-adjusted life years (DALY). The aim of this systematic review is to
      give an overview of the information available about different countries and
      periods for which DALYs were calculated and how the different results are
      comparable. One of the most important transmission pathways for Campylobacter
      spp. is food. Therefore, special attention was given to studies that only
      estimated the foodborne disease burden of Campylobacter bacteria. With a
      systematic search for the period 1/1996-6/2016, one worldwide and 21 country
      specific publications of the WHO were identified. Because of the different
      methods and the quality of the different data sets, the estimated results of all
      Campylobacter health outcomes of the country-specific studies vary from 0.4 DALYs
      per 100000 people in France to 109 DALY per population in Poland. The calculation
      of the attributable foodborne disease burden was based on the estimations of the
      incidences of all Campylobacter health outcomes with the associated uncertainty
      for each result. So the estimations of the foodborne disease burden show a large
      range from 0.5 DALYs per 100000 people in Greek to 21.2 DALYs per 100000 people
      in New Zealand. This span can only be partially explained by the country-specific
      variability in the food production, the consumption behavior and the incidence of
      Campylobacter bacteria.

PMID- 29216671
TI  - New Advances in Surgical Approaches for Total Knee Arthroplasty.

PMID- 29216672
TI  - Conservative Management after Intraoperative Over-Release of the Medial
      Collateral Ligament from its Tibial Insertion Site in Patients Undergoing Total
      Knee Arthroplasty.
AB  - During varus deformity correction in a patient undergoing total knee arthroplasty
      (TKA), the medial collateral ligament (MCL) could get completely detached from
      its distal insertion site. Our aim was to evaluate the (1) mid-term clinical
      outcome and implant survival after conservative treatment in patients with
      intraoperatively over-released MCL and (2) preoperative risk factors for MCL over
      release. A retrospective study was conducted on patients who had undergone a
      primary TKA between 2001 and 2006. The number of knees with intraoperative MCL
      over-release (over-released group) was 47 (40 patients); we compared these with
      the knees that had intact MCL (intact group, 502 knees). Simple anchoring of MCL
      was performed with no additional protection. The postoperative clinical outcome
      and implant survival were compared. Risk factors for MCL over-release were
      identified using multivariate analysis. The average follow-up period was 7.5
      years. The mean Knee Society score of the over-released group improved from 23.3
      to 92.7 and it was not significantly different from the intact group. Three cases
      of aseptic loosening occurred in the over-released group and 19 in the intact
      group (p = 0.423). The survival rates of the implant were 94.4% and 96.1%,
      respectively, at 13 years postoperatively. Multivariate analysis showed
      preoperative femoral-tibial angle as the only risk factor for over-release. This
      study showed that even MCL was over-released inadvertently, but it did not affect
      the clinical outcome. Preoperative femoral-tibial angle was the only predictable
      risk factor for MCL over-release.

PMID- 29216673
TI  - Factors Affecting Longer Surgical Times in Total Knee Arthroplasty for Obese
      Patients-A Comparative Study between High- and Nonhigh-Volume Surgeons.
AB  - Obesity has a negative influence on surgical times in total knee arthroplasty
      (TKA). Our purpose in this multicenter study was to compare surgical times
      between high- (HV) and nonhigh-volume (NHV) surgeons and clarify the important
      factors affecting longer surgical times in primary TKA for obese patients. A
      total of 798 knees, average age 75.1 years, were enrolled. All TKAs were done
      using the same measured resection technique by 25 surgeons at 12 facilities and
      were divided into three groups based on body mass index (kg/m2) of the patients
      (Group A: <24.9, Group B: 25-29.9, Group C: >=30). Operative techniques including
      four surgical steps (surgical exposure, bone cutting, trial and fixation of the
      permanent component, and wound closure) were evaluated both in HV and NHV
      surgeons. In classifying surgeon volume, HV surgeons had performed >100 TKAs
      annually for many years, and other surgeons who had performed <100 TKAs annually
      were defined as NHV surgeons. Patient demographics, surgical details, and
      surgical times in each phase were compared using nonrepeated measures of analysis
      of variance and a post hoc Student-Newman-Keuls test. A total of 331, 327, 140
      TKAs were allocated to Groups A, B, C, respectively. Regarding patient
      demographics, patients in Group C were younger and had the worst ranges of
      motion. The longest surgical time was observed in Group C of NHV surgeons (p <
      0.05). Concerning each surgical phase, surgeons took much more time in surgical
      exposure and fixation of the permanent component for obese patients in NHV
      surgeons (p < 0.05). Our results suggest that younger age and lower range of
      motion were observed in obese patients, which led to longer surgical times. In
      addition, NHV surgeons took much time in surgical exposure and fixation of the
      permanent component for obese patients, while surgical time was similar among
      groups for HV surgeons.

PMID- 29216674
TI  - Radiographic Morphology and Method for Localization of the Adductor Tubercle on
      Anterior-Posterior Knee Radiographs.
AB  - The adductor tubercle (AT) is a landmark for joint line identification in knee
      arthroplasty. Up to now, there has not been a dedicated study to define its
      morphology on an anterior-posterior (AP) radiograph. As a result, radiographic
      localization of the AT has been inconsistent and confusing. Ten bone specimens,
      each with the AT labeled with a metal marker, were radiographed to demonstrate
      the AT appearance on AP radiographs. Based on this knowledge, a method to locate
      the AT was developed. A total of 200 clinical radiographs were examined to
      further confirm the observed radiographic morphology with emphasis on the
      visibility of the AT and its association with the rotational status of the knee
      on radiographs. One hundred of them were used to test the reliability of this
      method of AT identification. Of the 200 ATs, 153 (76%) were clearly visible on
      radiographs as a faint pyramid-shaped shadow protruding outward from the
      inflexion point of the concave-convex silhouette over the femoral shaft-condylar
      junction, allowing direct identification. For invisible ATs (24%), this inflexion
      point was found to be a useful surrogate landmark for their identification.
      Locating the AT using this technique showed a good intra- and interobserver
      reliabilities. The proposed method may be valuable for the consistent use of this
      landmark in joint line identification on radiographs.

PMID- 29216675
TI  - Validation of a New Web-Based System for Point-of-Care Implant Documentation in
      Total Knee Arthroplasty.
AB  - Implant documentation in total knee arthroplasty (TKA) must be both accurate and
      comprehensive. A new system enables surgeons to complete a secure, web-based
      operative report for each surgery. This study evaluated implant documentation
      using this system and hypothesized that it would be as reliable as the current
      standard. This was a retrospective study of all primary and revision TKA
      performed at a single academic institution from January 1, 2015 to March 31,
      2015, by eight adult reconstruction surgeons who used the web-based system.
      Electronic medical records and implant logbooks were chosen as a composite
      standard reference for implant documentation. Cohen's kappa statistic and
      Pearson's correlation coefficients were used to determine agreement between the
      system and the standard reference. Mean kappa value for entire system was 0.916
      +/- 0.152 (p = 0.015) indicating "almost perfect" agreement (as per Landis and
      Koch's method) with standard reference. Pearson's correlation coefficient was
      0.926 +/- 0.147 (p = 0.021) further corroborating this excellent agreement. There
      was "substantial" or "fair" agreement for items pertaining to cement and
      augments. Overall, sensitivity was 0.98 (95% confidence interval: 0.71-0.98) and
      specificity 0.93 (95% confidence interval: 0.53-0.98) indicating that the system
      was very effective at documenting whether or not an implant was placed. The
      system exhibited significantly greater sensitivity than specificity (p = 0.027).
      This study demonstrated excellent performance of this novel system in point-of
      care TKA implant documentation. Further research is needed to validate its use in
      arthroplasty of other joints and its potential for documentation of biomedical
      device implantation in other fields such as cardiothoracic surgery and
      gastroenterology.

PMID- 29216676
TI  - Effect of Obesity on Total Knee Arthroplasty Costs and Revision Rate.
AB  - An increasing number of total knee arthroplasties (TKAs) are performed on obese
      patients. It is imperative to remain up to date on the effect of obesity on
      surgical outcomes and reimbursement trends. The purpose of this study was to
      evaluate the impact different severities of obesity have on primary and revision
      TKA, specifically: (1) incidence and trends over time; (2) annual growth rate;
      and (3) admission costs from 2010 to 2014. A retrospective review of a large
      commercial private payer database within the PearlDiver Supercomputer application
      (Warsaw, IN) of TKA procedures was conducted. Patients who underwent TKA and
      subsequent revision were identified by Current Procedural Terminology (CPT) and
      ninth revision International Classification of Disease (ICD-9) codes. The index
      procedure was linked with ICD-9 codes for body mass indexes (BMIs) from <19 to
      >70. Statistical analysis was primarily descriptive to demonstrate the revision
      incidence and reimbursement deviations due to BMI. Compound annual growth rate
      (CAGR) was also calculated. Our query returned a total of 87,607 TKA patients
      within the study BMI ranges. The majority of patients had a BMI of 40 to 44.9
      (12.2%) and least in the BMI >70 (0.2%) range. BMI of 40 to 44.9 had the highest
      overall 5-year mean reimbursement of $11,521 and the highest overall mean 5-year
      deviation from normal BMI (19-24) patients of $3,300. The incidence and burden of
      TKA revision was highest in patients with a BMI of 60 to 69.9 (21 and 17.3%,
      respectively). Average 5-year revision reimbursement and deviation from normal
      BMI (19-24) was highest in patients with a BMI of 40 to 44.9 ($13,883 and $4,030,
      respectively). The number of obese patients receiving TKA is steadily rising. The
      cost of treating obese patients rises as BMI deviates from normal, as does the
      incidence of revision surgery. Therefore, surgeons must be active in counseling
      patients on weight optimization as part of preoperative standard of care.

PMID- 29216677
TI  - Impact of Clinical Presentation on Imaging Evaluation to Direct Effective
      Treatment Strategies.
AB  - A multitude of musculoskeletal disorders of the knee are commonly encountered in
      clinical practice. Ensuring an accurate diagnosis can be challenging. It is
      critical to establish a thoughtful and systematic approach to assessing the
      patient using history and physical exam followed by appropriate imaging studies.
      The physical exam may be complicated due to various test maneuvers designed to
      help make the diagnosis. It is also important to understand the limitations of
      each physical exam maneuver. When appropriate, imaging is obtained to help make
      the diagnosis and guide treatment. There are various imaging examinations to
      choose from when evaluating the knee, including X-rays, computed tomography,
      magnetic resonance imaging, and ultrasound. An algorithmic approach to choosing
      the best imaging study is often helpful to avoid unnecessary costs and burden to
      the patients. The combination of a thorough clinical assessment and appropriate
      imaging examinations will result in accurate diagnosis, which directs proper
      treatment.

PMID- 29216678
TI  - [Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German
      Respiratory Society and the German Atemwegsliga in Cooperation with the
      Paediatric Respiratory Society and the Austrian Society of Pneumology].
AB  - The present guideline is a new version and an update of the guideline for the
      diagnosis and treatment of asthma, which replaces the previous version for german
      speaking countries from the year 2006. The wealth of new data on the
      pathophysiology and the phenotypes of asthma, and the expanded spectrum of
      diagnostic and therapeutic options necessitated a new version and an update. This
      guideline presents the current, evidence-based recommendations for the diagnosis
      and treatment of asthma, for children and adolescents as well as for adults with
      asthma.

PMID- 29216679
TI  - The role of extracorporeal membrane oxygenator therapy in the setting of Type A
      aortic dissection.
AB  - BACKGROUND AND AIM: Patients presenting with type A aortic dissection (TAAD)
      present with a wide clinical spectrum ranging from hemodynamic stability to
      multiorgan malperfusion with cardiovascular collapse. Extracorporeal membrane
      oxygenator (ECMO) therapy is increasingly being utilized as salvage therapy in
      patients with acute cardiopulmonary failure and for post-cardiotomy shock. We
      sought to determine the utility of ECMO implementation post-TAAD repair. METHODS:
      The Pennsylvania Health Care Cost Containment Council (PHC4) database, maintained
      by an independently functioning state agency, was retrospectively reviewed from
      2004 to 2014. Patients with a primary diagnosis of aortic dissection requiring
      ECMO support during the same hospital visit were included in the analysis.
      RESULTS: Thirty-nine patients were identified with diagnosis/procedure codes for
      TAAD repair and ECMO, of which four patients did not undergo TAAD repair. Of the
      remaining 35, 31 patients underwent open repair, and four patients underwent
      TEVAR. ECMO was instituted on the same day of TAAD surgery in 27 (69.2%)
      patients, and on post-operative day >1 in eight (20.5%) patients. Overall
      mortality in patients who were on ECMO the same day was 88.9% and 87.5% when it
      was done after the first post-operative day. All four patients with TAAD who
      underwent ECMO only died. Median time from ECMO implantation to death was 1.0
      day. CONCLUSIONS: Requirement for ECMO support in acute aortic dissection is
      associated with extremely high mortality irrespective of when the intervention is
      performed.

PMID- 29216680
TI  - How to do liver transplantation using renoportal bypass.

PMID- 29216681
TI  - An unfortunate soul: a rare presentation of an uncommon pathology for upper
      gastrointestinal bleeding.

PMID- 29216682
TI  - Simultaneous determination and validation of emtricitabine, rilpivirine and
      tenofovir from biological samples using LC and CE methods.
AB  - A combination of antiretroviral agents is frequently used in effective treatment
      of the human immunodeficiency virus infection. In this study, two different
      separation methods are presented for the simultaneous determination of
      emtricitabine, rilpivirine and tenofovir from raw materials and urine samples.
      Developed liquid chromatography and capillary electrophoresis methods were
      thoroughly optimized for high analytical performances. Optimization of multiple
      variables at the same time by performing a minimum number of experiments was
      achieved by the Box-Behnken design, which is an experimental design in response
      surface methodology, in capillary electrophoresis. The results of the
      experimental design ensure minimum analysis time with well-separated analytes.
      Separation conditions, such as different stationary phases, pH level, organic
      modifiers and temperatures in liquid chromatography method, were also optimized.
      In particular, among stationary phases, the core-shell column especially enhanced
      the effectiveness of separation in liquid chromatography. Both methods were fully
      validated and applied to real samples. The main advantage of the developed
      methods is the separation of the drug combination in a short time with high
      efficiency and without any time-consuming steps.

PMID- 29216683
TI  - Human perforin gene variation is geographically distributed.
AB  - BACKGROUND: Deleterious mutations in PRF1 result in lethal, childhood disease,
      familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, not all
      mutations in PRF1 are deleterious and result in FHL 2. Currently, these
      nondeleterious mutations are being investigated in the onset of numerous
      disorders, such as lymphomas and diabetes. Yet, there is still an overwhelmingly
      large amount of PRF1 mutations that are not associated with disease. METHODS: We
      conducted a post hoc analysis of the PRF1 mutations in the coding region using
      the recently published Exome Aggregation Consortium genomes, Leiden Open
      Variation Database, NCBI SNP database, and primary literature to better
      understand PRF1 variation in the human population. RESULTS: This study catalogs
      460 PRF1 mutations in the coding region, and demonstrates PRF1 is more variant
      then previously predicted. We identify key PRF1 mutations with high allelic
      frequency and are only found in certain populations. Additionally, we define PRF1
      SNVs are geographically distributed. CONCLUSIONS: This study concludes with a
      novel hypothesis that nondeleterious mutation in PRF1, which decreases perforin
      expression and/or activity, may be an example of selective advantage in the
      context of environmental stressors prevalent near the equator. Our studies
      illustrate how perforin deficiency can be protective from injuries resulting in
      blood-brain barrier (BBB) disruption.

PMID- 29216684
TI  - The impact of Corynebacterium glucuronolyticum on semen parameters: a prospective
      pre-post-treatment study.
AB  - Corynebacterium glucuronolyticum (C. glucuronolyticum) is a rare isolate that is
      only recently being acknowledged as a potential urogenital pathogen. The
      bibliographical references on this bacterial species are scarce, and its
      influence on all semen parameters was hitherto unknown - therefore, the aim of
      this study was to evaluate its effects on a range of sperm quality parameters. A
      prospective approach to compare semen parameters before and after treatment was
      used in this study. C. glucuronolyticum in semen specimens was identified using
      analytical profile index biotyping system (API Coryne) and additionally confirmed
      by matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry
      (MALDI-TOF MS), with the determination of antimicrobial susceptibility by Kirby
      Bauer method. Semen analysis was performed according to the criteria from the
      World Health Organization (with the use of Tygerberg method of sperm morphology
      categorization). Very strict inclusion criteria for participants also included
      detailed medical history and urological evaluation. From a total of 2169 screened
      semen specimens, the inclusion rate for participants with C. glucuronolyticum
      that satisfied all the criteria was 1.01%. Antibiogram-guided treatment of the
      infection with ensuing microbiological clearance has shown that the resolution of
      the infection correlates with statistically significant improvement in the
      vitality of spermatozoa, but also with a lower number of neck and mid-piece
      defects. Parameters such as sperm count, motility and normal morphology were not
      affected. In addition, susceptibility testing revealed a trend towards
      ciprofloxacin resistance, which is something that should be considered when
      selecting an optimal treatment approach. Albeit it is rarely encountered as a
      monoisolate in significant quantities, C. glucuronolyticum may negatively
      influence certain sperm parameters; therefore, it has to be taken into account in
      the microbiological analysis of urogenital samples.

PMID- 29216685
TI  - Patient compliance with surveillance colonoscopy: patient factors and the use of
      a graded recall system.
AB  - BACKGROUND: Surveillance colonoscopy allows for the early detection and improved
      treatment outcomes in colorectal neoplasms but compliance rates and factors
      require further investigation. METHODS: This is a retrospective cohort study
      examining 816 patients recalled for surveillance colonoscopy at an Australian
      colorectal practice over a 6-month period. Primary outcome was compliance with
      colonoscopy within 12 months of recall. The secondary outcome of this study was
      to identify factors affecting compliance including patient factors and the
      practices' graded recall system. RESULTS: A total of 715 patients (87.6%) were
      compliant with recall requests for repeat colonoscopy. Significantly higher
      compliance rates were noted with a personal history of adenomatous polyps (90.9%
      versus 85.6%, P = 0.025). Those with private insurance or Department of Veterans
      Affairs were more likely to be compliant than those publicly funded (89.0% versus
      93.3% versus 79.0%, P = 0.007). No statistically significant difference in
      compliance was shown with a personal history of colorectal cancer, diverticular
      disease, perianal disease, National Health and Medical Research Council risk
      category, gender, time associated with the practice or the clinician. There was a
      significant positive correlation between the number of letters sent and
      compliance with recall, with 61.8% being compliant after a single letter, and a
      final cumulative compliance after five letters of 87.6% (R = 0.882, P = 0.048).
      CONCLUSION: A graded recall system can achieve compliance rates as high as 87.6%
      compared to a single letter only achieving 61.8% compliance. A history of
      adenomatous polyps and insurance status were the only factors shown to result in
      higher recall compliance.

PMID- 29216687
TI  - Editorial Comment to High neutrophil-to-lymphocyte ratio predicts worse overall
      survival in patients with advanced/metastatic urothelial bladder cancer.

PMID- 29216688
TI  - Symptomatic cardiac hemangioma resected on the first day of life.
AB  - Cardiac tumors are extremely rare in neonates. We describe the case of a right
      atrial hemangioma in a neonate diagnosed prenatally and successfully operated on
      the first day of life.

PMID- 29216686
TI  - Congenital bilateral absence of the vas deferens as an atypical form of cystic
      fibrosis: reproductive implications and genetic counseling.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) is found in 1% to 2% of
      males with infertility and is present in 6% of obstructive azoospermia cases.
      Nearly 95% of men with cystic fibrosis (CF, an autosomal recessive disorder) have
      CBAVD. There are genetic links between CBAVD and CF. Some mutations in the gene
      encoding cystic fibrosis transmembrane conductance regulator (CFTR) can lead to
      CBAVD as a monosymptomatic form of CF. With the use of assisted reproductive
      techniques (ART), especially testicular or epididymal sperm aspiration,
      intracytoplasmic sperm injection, and in vitro fertilization, it is possible that
      men with CBAVD can produce offspring. Therefore, genetic counseling should be
      offered to couples undergoing ART to discuss the probability of having offspring
      that carry CFTR gene mutations. The aim of this review was to present the main
      cause of CBAVD, to call attention to its implications for assisted reproduction,
      and to show the importance of genetic counseling for couples where men have
      CBAVD, as they can have offspring with a lethal disease.

PMID- 29216689
TI  - [Doxycycline as an adjuvant in postsurgical recovery of rotator cuff injuries.
      One-year follow-up].
AB  - BACKGROUND: The severity and progression of rotator cuff tears have forced
      research on new treatment pathways such as metalloprotease inhibition, which has
      shown a reduction in healing time and improvement in the structure of collagen
      fibers. OBJECTIVE: To evaluate the use of doxycycline as a healing enhancer in
      rotator cuff tears after surgical treatment. MATERIAL AND METHODS: 20 patients
      were included; they were divided into two groups, 10 with the use of doxycycline
      and 10 without it after arthroscopic repair with one-year follow-up. Doxycycline
      was given orally, 100 mg once a day for one month. Every subject in the test was
      diagnosed with rotator cuff tear confirmed by MRI with Patte and Goutallier
      scores below 2. We used the arthroscopic double row technique. Post-op follow-up
      was 12 months with clinical scales (UCLA, Constant and forward flexion strength).
      RESULTS: Both groups reported almost complete healing of rotator cuff tears after
      surgical treatment during the twelve months of follow-up; forward flexion
      strength was the only score that reported improvement in the doxycycline group
      during every check-up. DISCUSSION: Doxycycline use after arthroscopic cuff tear
      repair could improve the clinical outcome, but we do not know how yet; however
      larger sample and randomized trials should be developed.

PMID- 29216690
TI  - [Osteochondromas: introducing the subungual osteochondroma].
AB  - INTRODUCTION: Subungual osteochondromas are benign tumors of the sub- or
      periungual region, causing lifting, ulceration and deformity at that level.
      OBJECTIVE: To research the incidence of subungual osteochondromas in a specific
      pediatric population. MATERIAL AND METHODS: Retrospective, transversal,
      descriptive and observational study based on the review of records with a
      histopathological result of osteochondroma from 2001 to 2014. RESULTS: The
      pathological assessment featured four osteochondromas that corresponded to the
      subungual presentation, with an equal gender distribution of 1:1, an average age
      of 9.5 years, right: left ratio of 3:1; the 4th finger was the most affected.
      DISCUSSION: Subungual osteochondroma has an incidence of 8.5% of all
      osteochondromas.

PMID- 29216691
TI  - Lumbar fusion with collagen type I and polyvinylpyrrolidone in combination with
      autograft. An experimental study in New Zealand rabbits.
AB  - INTRODUCTION: Multiple strategies have been developed looking for upgrading the
      consolidation rate of spine arthrodesis with autolog bone graft, but no evidence
      exists that adhesion with Collagen type 1 and polyvinylpyrrolidone (FibroquelMR)
      have application on this field. OBJECTIVE: Determine if collagen type 1 +
      Polyvinylpyrrolidone are effective as bone enhancer in posterolateral arthrodesis
      on rabbits. METHOD: Posterolateral arthrodesis in 15 New Zealand rabbits on level
      L5-L6 using autolog bone graft in left side (control group) and autolog bone
      graft + 1 ml FibroquelMR (study group) in right side of arthrodesis. Euthanasia
      and block resection of lumbar segment eight weeks post surgery. Radiographic
      analysis, manual exploration and light microscopy of fussed segments. RESULTS:
      Radiographic consolidation was observed in 80% in control group and 95% in study
      group, interleaved trabecular pattern with bone continuity and normal
      characteristics in 12 left sides and 14 right sides. CONCLUSION: Collagen type 1
      and polyvinylpyrrolidone use is likely to have positive effect in bone
      consolidation process, therefore it can be recommended to use it as a bone
      enhancer.

PMID- 29216692
TI  - [Clinical and radiographic evaluation of a new percutaneous technique for
      moderate to severe hallux valgus deformity].
AB  - : Hallux valgus is considered the most common musculoskeletal deformity, with a
      prevalence of 88%. There are more than 130 surgical techniques for its treatment;
      currently, percutaneous ones are popular; however, they do not take into account
      the metatarsal-phalangeal correction angle. The aim of this study is to propose a
      modified technique for the correction of the percutaneous metatarsal-phalangeal
      and inter-metatarsal angles and to evaluate its clinical and radiological
      results. MATERIAL AND METHODS: An experimental, prospective and longitudinal
      study in 10 patients with moderate to severe hallux valgus according to the
      classification of Coughlin and Mann were collected; the results were evaluated
      with the AOFAS scale at 15, 30, 60 and 90 days. The McBride technique and the
      technique of percutaneous anchor with the proposed amendment were performed.
      RESULTS: The AOFAS scale was applied as described, finding a progressive increase
      of the rating; the average correction of the inter-metatarsal angle was 8.8
      degrees and of the metatarsal-phalangeal, 9.12. DISCUSSION: The modified
      technique of percutaneous anchor showed clear clinical and radiographic
      improvements in the short term. Our modified technique is proposed for future
      projects, including a large sample with long-term follow-up.

PMID- 29216693
TI  - A comparative study in patients with fractures of the lower limbs between
      rivaroxaban versus enoxaparin and its impact on bone healing time.
AB  - BACKGROUND: Each year it is estimated in the United States an approximate of 8
      million fractures; 5 to 10% develop delayed union or absence of periosteal new
      bone. There are several factors that can cause delay in fracture healing, among
      the well known, is the use of prophylactic antithrombotic therapy for deep vein
      thrombosis (DVT). DVT appears in 40 to 60% of the patients undergoing orthopedic
      surgery without prophylactic antithrombotic therapy. The goal of this study was
      to assess whether there is a difference in time of bone healing in lower limb
      fractures (femur and tibia) comparing rivaroxaban to enoxaparin as the
      prophylactic antithrombotic management. MATERIAL AND METHODS: We present a
      retrospective observational and analytic study in a sample of cases. It is a
      cross-sectional study with patient data from the database of the American British
      Cowdray (ABC) Medical Center. We included patients with femur and tibia fractures
      under antithrombotic prophylactic management with rivaroxaban or enoxaparin
      during the period of January 2011 to December 2012. Our sample included 32
      patients separated into two groups. Students t-test was used for comparing
      parametric variables and the Mann-Whitney U test for nonparametric variables.
      Linear regression model was preformed considering the variables related to the
      time it took the fracture to heal. RESULTS: All fractures consolidated in a time
      of 13 and 14 weeks for rivaroxaban and enoxaparin respectively (p = 0.67).
      DISCUSSION: We found no difference in bone healing time for lower limb fractures
      in patients receiving antithrombotic prophylaxis treatment comparing rivaroxaban
      with enoxaparin.

PMID- 29216694
TI  - [Evidence level and grade of recommendation of the Ponseti method for
      arthrogryposis-related syndromic talipes equinovarus and Moebius syndrome: a
      systematic review].
AB  - BACKGROUND: Adduct congenital talipes equinovarus (CTE) or clubfoot is a common
      musculoskeletal malformation affecting between 1 and 4.5 out of every 1000 live
      births. It is usually associated with arthrogryposis and Moebius syndrome with
      the latter two being more difficult to treat as they require aggressive surgery
      to achieve a plantigrade foot. We therefore ask what is the evidence level and
      grade of recommendation of the Ponseti method to treat syndromic talipes
      equinovarus resulting from arthrogryposis and Moebius syndrome. METHODS:
      Systematic review according to the recommendations of the Cochrane group
      identifying medical subheadings (MeSH) and of the Boolean method to identify the
      articles that met the selection criteria through the search of primary sources
      such as OVID, Cochrane, EBSCOhost, Elsevier, Medigraphic. RESULTS: A total of six
      papers met the selection criteria through the search in the primary sources. Five
      of them address the treatment of adduct CTE with the Ponseti method in patients
      with arthrogryposis, and one in patients with Moebius. Evidence levels and grades
      of recommendation of these papers were: IV-D (3), III-D (1) y II (B).
      CONCLUSIONS: The Ponseti method is an first-line treatment for arthrogryposis and
      Moebius syndrome. It is unexpensive, non-invasive and does not require a
      physician to perform it (however, it does require trained staff). Its use is
      recommended as it avoids extensive surgeries and medical complications that go
      beyond the hospitals economic possibilities.

PMID- 29216695
TI  - [Factor associated in the failure of the ostheosyntesis of transtrocantheric
      fractures].
AB  - : Pertrochanteric fractures account approximately a half of the proximal femoral
      fractures. Incidence of these fractures is highest in women, age > 65 years and
      presents a mortality rate of 14 to 50%. Treatment goals include stable fixation,
      immediate mobilization and restore activities. Complications after treatment
      present in 17% and include: nonunion, cut out and varus displacement. OBJECTIVE:
      Correlation between complications after surgical treatment and presence of
      instability, inadequate reduction, Tip Apex Index (TAI) > 25 mm, Tip Apex Index
      to calcar (TAIcal) > 20 mm and parker index. MATERIAL AND METHODS: A case control
      study was conducted in patients with pertrochanteric fractures treated between
      January 2009 and December 2014, 91 patients were included and complications were
      measured up to 6 months after surgery. RESULTS: 27 patients were included in
      group 1, which were the ones who presented complications. Values of TAI measured
      in this group were 13.7 to 45 mm, and were significantly higher than group 2.
      Position of the blade/screw central in the lateral view and inferior in the AP
      view didn't present complications. CONCLUSIONS: We found 27 patients with
      complications in the follow up (29%). Initial reduction and stability is
      determinant to success. We recommend the use of proximal femoral nail in all
      unstable fractures. It is confirmed that TAI > 25 mm as a predictor of failure.

PMID- 29216696
TI  - [Undetected traumatic posterior glenohumeral dislocation].
AB  - INTRODUCTION: Glenohumeral dislocation (GHD) is frequent, but traumatic posterior
      glenohumeral dislocation (TPGHD) is rare, with an incidence of 1-4% of all GHD.
      The diagnosis is a challenge: sometimes, it can be omitted due to incorrect
      diagnosis, absence of consideration in the differential diagnosis, suboptimal
      radiographic evaluation and an absence of characteristic signs and symptoms;
      missed diagnosis reaches 60-79% and the diagnosis can delay from 24 hours to a
      year. OBJECTIVE: To transmit previous experiences to provide support for better
      diagnosing TPGHD, favoring appropriate attention. CASE REPORTS: Case 1. 34-year
      old male. Delayed diagnosis of left TPGHD in the 4th week. Reverse Hill-Sachs <
      25%. Closed reduction, immobilization for four weeks. Follow-up at week 20, good
      functional recovery (UCLA = 32). Case 2. 32-year-old male. Eight months with
      undiagnosed left TPGHD. Reverse Hill-Sachs 25%. Open reduction, immobilization
      for four weeks. Eight-month post-surgical follow-up. Good functional recovery
      (UCLA = 29). DISCUSSION: The diagnosis of TPGHD is difficult because of its lack
      of frequency. Even with delayed diagnosis-treatment, evolution can be favorable
      provided that the reverse Hill-Sachs injury is 25% or minor. To avoid a delayed
      diagnosis and inadequate attention, we must always consider the injury mechanism,
      physical examination with the arm fixed in internal rotation, clinical suspicion
      in functional deficit for external rotation, flexion and abduction, radiographic
      studies including true AP and scapula lateral (Y view).

PMID- 29216697
TI  - [Case report: total hip replacement in osteogenesis imperfecta].
AB  - We study, apropos of a case, a total hip arthroplasty in a patient with
      osteogenesis imperfecta. The characteristics of this disease, such as high risk
      of fracture and the presence of deformities, make this surgery a challenge for
      the orthopedic surgeon. In this manuscript, we review for the first time in this
      indication the preoperative planning and the selection of implants, with special
      emphasis on measures for the prevention of complications.

PMID- 29216698
TI  - [Why English?]
AB  - No Abstract available.

PMID- 29216699
TI  - [Diagnostic value of a predictive model for complete ruptures of the rotator cuff
      associated to subacromial impingement].
AB  - : Pathology related to the rotator cuff remains among the most prevalent
      musculoskeletal diseases. There is an increasing need for imaging studies (MRI,
      US, arthroscopy) to test the diagnostic performance of the medical history and
      physical examination. OBJECTIVE: To prove the diagnostic value of a clinical
      radiographic predictive model to find complete ruptures of the rotator cuff.
      MATERIAL AND METHODS: Descriptive, observational, prospective, transversal and
      analytical study. Fifty-five patients with preoperative shoulder pain were
      evaluated with 13 predictive variables: age > 50 years, nocturnal pain, muscle
      weakness, clinical signs of Neer, Hawkins, Jobe, external rotation lag (ERLS),
      belly-press, bear hug, and lift-off, radiographic measurement of subacromial
      space, acromial index and critical shoulder angle. Sensitivity, specificity, and
      positive and negative predictive values were measured in each variable, comparing
      the results of each one against the postoperative findings. RESULTS: Of the 55
      patients evaluated, 42 had a complete rupture of the rotator cuff in the
      postoperative period. The eight variables with a higher diagnostic value were
      selected and a ROC curve was performed, providing an area under the curve of
      0.88. CONCLUSIONS: This predictive model uses eight variables (age > 50 years,
      nocturnal pain, muscle weakness, Jobe, Hawkins, ERLS, subacromial space <= 6 mm,
      and critical shoulder angle > 35 degrees ), which together add the predictive
      value of 0.88 (AUC) to diagnose complete ruptures of the supraspinatus tendon.

PMID- 29216700
TI  - [Assessment of pain, function and complications after minimelly invasive
      decompression of morton's neuroma using a dorsal approach in 16 patients].
AB  - BACKGROUND: The purpose of this paper is to assess pain, function and
      complications after decompression of Mortons neuroma using a minimally invasive
      dorsal approach. METHOD AND RESULTS: 16 patients who underwent 19 decompressions
      were followed-up for 18 months. Pain was assessed with the visual analog scale
      (VAS), and function was assessed with the American Orthopedic Foot and Ankle
      Society (AOFAS) scale. Data was analyzed with the Student t test for related
      samples, which yielded a p value 0.05. The possible postoperative complications
      assessed were: skin problems, infections, wound dehiscence, delayed bone healing
      and recurrence. CONCLUSION: Minimally invasive decompression of Mortons neuroma
      is a procedure that provides pain relief and improvement in function, with a low
      complication rate.

PMID- 29216701
TI  - [A cadaveric study of a new capsulorrhaphy for the surgical treatment of hallux
      valgus].
AB  - BACKGROUND: There are many surgical options for the treatment of hallux valgus in
      combination with capsular repairs for the correction of hallux valgus. MATERIAL
      AND METHODS: This report corresponds to a descriptive study where a new
      capsulorrhaphy technique in hallux valgus is proposed. Six dissections were
      performed on cadavers with hallux valgus deformity using the following surgical
      technique: medial approach on the first toe longitudinally, dissecting by planes
      and locating the metatarsophalangeal joint capsule; it was incised
      longitudinally. The capsule was separated and an exostectomy of the first
      metatarsal head was done, the edges were regularized and a release of the
      abductor hallucis was performed. Later, the capsular remnant was resected and
      repaired. RESULTS: Six cadaveric feet with hallux valgus were studied, five with
      mild deformity, one with moderate deformity, one foot with the 2nd finger on
      supraductus. DISCUSSION: Many capsular repairs have been reported in the
      literature, including "L", triangular, "V-Y", rectangular, with satisfactory
      results, along with osteotomy of the first metatarsal. In this report, a new
      capsular repair was described. CONCLUSION: Applying this new capsular repair, we
      reduced the metatarsophalangeal and intermetatarsal angles and achieved a
      capsular closure with suitable tension; the metatarsophalangeal joint mobility
      was preserved.

PMID- 29216702
TI  - [Sonographic evaluation of Achilles tendon healing in tenotomies for congenital
      clubfoot and Ponsetis treatment. A 12-week follow-up].
AB  - OBJECTIVE: The aim of this study was to determine the healing time of Achilles
      tendon in pediatric patients treated with Achilles tenotomy with the Ponseti
      method in Shriners Childrens Hospital of Mexico, AC. MATERIAL AND METHODS:
      Experimental, analytical, prospective, longitudinal study of patients with a
      diagnosis of idiopathic congenital clubfoot treated with the Ponseti method with
      serial static and dynamic evaluation by ultrasound in real time with a Siemens
      Diagnostic Ultrasound System Sonoline 650, linear transducer 10.5 MHz of Achilles
      tendon before tenotomy and at three, six, nine and 12 weeks after the surgical
      treatment. RESULTS: A sample of 23 patients, 16 male and seven female, 16 with
      unilateral and seven with bilateral pathology was obtained, for a total of 39
      feet, 18 right and 21 left, with a mean age of 8.3 +/- 2.3 months. Before
      tenotomy, the width was 2.7 +/- 0.42 mm; in week three, the average was 3 +/-
      0.39 mm; at six weeks, 2.92 +/- 0.36 mm; ultrasound at nine weeks reported an
      average of 0.38 +/- 2.84 mm, and 2.82 +/- 0.39 mm at twelve weeks. They were
      compared using Students t presurgical width and at twelve weeks, without finding
      difference p 0.03. CONCLUSIONS: Although there is integrity at three weeks after
      Achilles tenotomy, complete repair is achieved at 12 weeks.

PMID- 29216703
TI  - [Effect of sports training in angular compartment of the lower limbs in children
      footballers aged 11 to 12 years old].
AB  - Anterior Cruciate Ligament (ACL) injury is an important cause of days lost in
      athletes. Most ACL injuries are non-contact and are associated with biomechanical
      risk factors that increase tension in the ACL: increased knee valgus (KV) and hip
      flexion (HF) and decreased flexion of knee (KF). Muscle around the knee
      contributes to knee stability, so fatigue produced by exercise could alter knee
      balance, increasing LCA tension. The aim of the study is to determine the angular
      behavior before and after a physical load for CF, RR and RV in children born in
      2002-2003. A non-randomized clinical trial was conducted. The sample consisted of
      50 students from soccer schools born between 2002 and 2003. The angular behavior
      of CF, RR and VR was compared, before and after performing standardized training.
      The angular behavior was measured by performing the DJ test with data obtained by
      inertial sensors. After exercise, the 3 variables increased, but only HF reached
      significant difference. Other important finding was the difference found in KV
      between the dominant leg and the support limb, at both times: rest and post
      exercise. It was concluded that the angular behavior of CF increases
      significantly in both limbs post-exercise and that preventive measures should be
      applied for the management of valgus in the supporting limb.

PMID- 29216704
TI  - [Prevalence of X-ray signs of femoroacetabular impingement in Mexican
      population].
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is a suggested diagnosis for pain
      in the hip in the absence of other apparent causes. It is thought to be a cause
      of progressive arthrosis of the hip. Our objective was to determine the
      prevalence of radiographic data of FAI in the adult population without hip
      pathology over a period of six months. MATERIAL AND METHODS: Analytical,
      observational, multicentric, ambispective and transverse study based on digital X
      rays analysis. Measurements of the lateral center-edge angle of Wiberg,
      acetabular inclination, Tonnis angle and the neck shaft angle of the proximal
      femur were made; a pistol grip deformity of the femoral head, the triangular
      index and the shape of the coxofemoral joint were also evaluated. RESULTS: From a
      total of 212 hips evaluated, 104 were in males and 108 in females, with an
      average age of 42.81 years; 21 had a pistol grip deformity and a positive
      triangular index for cam type. The pincer type was found in 12 hips. DISCUSSION:
      In this multicentric study, the FAI cam type predominated in men on the right
      side; the pincer type predominated in women on the left side; this is similar to
      what has been reported in other populations. This study is limited by the wide
      variation in the femoral rotation; as an advantage, it was randomly carried out
      and provides some data on the prevalence of deformities of the hip, not
      previously registered.

PMID- 29216705
TI  - [Functional results of open wedge osteotomies in lower limb angular deformities
      in teenagers].
AB  - OBJECTIVE: The aim of this study was to evaluate the functional and radiographic
      results of adolescent patients with angular deformities of the pelvic limbs
      treated with an open wedge osteotomy system. MATERIAL AND METHODS: Observational,
      prospective, analytical and cross-sectional study of patients with angular
      deformity of the pelvic limbs treated with an open wedge osteotomy. We made a
      radiographic evaluation of the femorotibial angle, MAD angle, lower limb
      discrepancy, and pre- and postoperative degrees of the rotational center of
      deformity (CORA), as well as a telephone survey of the postoperative functional
      evaluation IKDC 2000. RESULTS: It was a sample of 28 patients, 21 female and
      seven male, with a mean age of 15.3 years. Their diagnoses: idiopathic genu
      valgo, 10 cases; Blount disease, four; benign tumors (enchondromatosis and
      osteochondromatosis), three; hypophosphatemic rickets; three, among others, such
      as sequelae of septic arthritis of the knee, femoral hypoplasia, and fracture
      sequels. It was a total of 29 osteotomies, 17 of the tibia and 12 of the femur;
      17 osteotomies presented deviation to lateral of the mechanical axis, and 11,
      medial deviation, with a mean femorotibial angle of 17 and 7.35 (p 0.03),
      respectively. The mean initial discrepancy had an improvement of 0.5 cm.
      Postoperative IKDC in the subjective evaluation had an average of 95.3 points.
      CONCLUSIONS: The fixation of osteotomies with open wedge plates is an option with
      good clinical and radiographic results.

PMID- 29216706
TI  - [Intraarticular lesions associated with tibial fixation during anterior cruciate
      ligament reconstruction].
AB  - Anterior cruciate ligament reconstruction is a demanding procedure; complications
      may arise at any of its stages. This is the report of three cases in which the
      tibial fixation devices (IntraFix and Bio-IntraFix) led to intraarticular
      lesions. The complications were detected in one of the cases while the patient
      was still in the operating room and in the remaining two during the follow-up.
      All the patients had a stable knee, but all of them sustained chondral lesions
      resulting from the inadequate placement of the implants used for tibial fixation.
      Several suggestions to avoid the complications stemming from these devices are
      provided.

PMID- 29216707
TI  - [Femur fracture in a patient with dog-leg deformity secondary to arthrogryposis.
      Description of a unique osteosynthesis method].
AB  - The concept of arthrogryposis encompasses several conditions that share the
      presence of multiple congenital contractures. The knee is frequently involved and
      is an important cause of morbidity in these patients. Flexion contractures of the
      knee are the most common ones and have a worse prognosis than extension
      contractures. Different approaches are available to treat flexion contractures of
      the knee. Distal femoral extension osteotomy effectively corrects fixed flexion,
      but may lead to residual deformity. This iatrogenic deformity disrupts the
      anterior convexity of the femoral shaft and leads to serious problems in the
      subsequent management of orthopedic conditions. This is a case report of a
      patient with arthrogryposis and a femur deformity who sustained a supracondylar
      fracture. Managing the fracture was challenging due to a disruption in the normal
      architecture of the femur. This is a description of the osteosynthesis approach
      used to treat the fracture and the patients pre-existing deformity.

PMID- 29216708
TI  - [Letter to the Editor].
AB  - No Abstract available.

PMID- 29216709
TI  - Effect of Adjuvant Chemotherapy on Stage II Colon Cancer: Analysis of Korean
      National Data.
AB  - PURPOSE: Debates exist regarding the effectiveness of adjuvant chemotherapy for
      stage II colon cancer. This study aimed to investigate the current status of
      adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer
      patients by analyzing the National Quality Assessment data. Materials and
      Methods: A total of 7,880 patientswho underwent curative resection for stage II
      colon adenocarcinoma between January 2011 andDecember 2014 in Koreawere selected
      randomly as evaluation subjects for the quality assessment. The factors that
      influenced overall survival were identified. The high-risk group was defined as
      having at least one of the following: perforation/ obstruction, lymph node
      harvest less than 12, lymphovascular/perineural invasion, positive resection
      margin, poor differentiation, or pathologic T4 stage. RESULTS: The median follow
      up period was 38 months (range, 1 to 63 months). Chemotherapy was a favorable
      prognostic factor for either the high- (hazard ratio [HR], 0.76; 95% confidence
      interval [CI], 0.38 to 0.59; p < 0.001) or low-risk group (HR, 0.74; 95% CI, 0.61
      to 0.89; p=0.002) in multivariate analysis. This was also the case in patients
      over 70 years of age. The hazard ratio was significantly increased as the number
      of involved risk factors was increased in patients who didn't receive
      chemotherapy. Adding oxaliplatin showed no difference in survival (HR, 1.36; 95%
      CI, 0.91 to 2.03; p=0.132). CONCLUSION: Adjuvant chemotherapy can be recommended
      for stage II colon cancer patients, but the addition of oxaliplatin to the
      regimen must be selective.

PMID- 29216711
TI  - Electrocatalytic Reduction of Dioxygen to Hydrogen Peroxide by a Molecular
      Manganese Complex with a Bipyridine-Containing Schiff Base Ligand.
AB  - The synthesis and electrocatalytic reduction of dioxygen by a molecular
      manganese(III) complex with a tetradentate dianionic bipyridine-based ligand is
      reported. Electrochemical characterization indicates a Nernstian dependence on
      the added proton source for the reduction of Mn(III) to Mn(II). The resultant
      species is competent for the reduction of dioxygen to H2O2 with 81 +/- 4%
      Faradaic efficiency. Mechanistic studies suggest that the catalytically active
      species has been generated through the interaction of the added proton donor and
      the parent Mn complex, resulting in the protonation of a coordinated phenolate
      moiety following the single-electron reduction, generating a neutral species with
      a vacant coordination site at the metal center. As a consequence, the active
      catalyst has a pendent proton source in close proximity to the active site for
      subsequent intramolecular reactions.

PMID- 29216710
TI  - A Novel Prognostic Nomogram for Predicting Risks of Distant Failure in Patients
      with Invasive Breast Cancer Following Postoperative Adjuvant Radiotherapy.
AB  - PURPOSE: This study aimed to identify predictors for distant metastatic behavior
      and build a related prognostic nomogram in breast cancer. Materials and Methods:
      A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011
      were analyzed. To predict the probability of distant metastasis, a nomogram was
      constructed based on prognostic factors identified using a Cox proportional
      hazards model. RESULTS: The 7-year overall survival and 5-year post-progression
      survival of locoregional versus distant recurrence groups were 67.6% versus 39.1%
      (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed
      distant metastasis showed early and late mortality risk peaks within 3 and after
      5 years of follow-up, respectively, but a broad and low risk increment was
      observed in other patients with locoregional relapse. In multivariate analysis of
      distant metastasis-free interval, age (>= 45 years vs. < 45 years), molecular
      subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple
      negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3)
      were independently associated (p < 0.05 for all). Regarding the significant
      factors, a well-validated nomogram was established (concordance index, 0.812).
      The risk score level of patients with initial brain failure was higher than those
      of non-brain sites (p=0.029). CONCLUSION: The nomogram could be useful for
      predicting the individual probability of distant recurrence in breast cancer. In
      high-risk patients based on the risk scores, more aggressive systemic therapy and
      closer surveillance for metastatic failure should be considered.

PMID- 29216712
TI  - Synthesis of C2-Symmetric gem-Difluoromethylenated Angular Triquinanes.
AB  - A synthesis of symmetrical gem-difluoromethylenated angular triquinanes is
      described. The synthetic strategy involved sequential fluoride-catalyzed
      nucleophilic addition of PhSCF2SiMe3 (1) to 2,2-diallylated or 2,2
      dipropargylated indane-1,3-diones 2 followed by stereoselective radical
      cyclization of the resulting adducts 3 to provide the cyclized gem
      difluoromethylenated diquinanes 4 as a mixture of stereoisomers. Repeated
      addition of 1 to 4 followed by cyclization resulted in the stereoselective
      synthesis of the desired C2-symmetric gem-difluoromethylenated angular
      triquinanes 6 in good yields with high stereoselectivity.

PMID- 29216713
TI  - Poly(2-oxazoline)-Pterostilbene Block Copolymer Nanoparticles for Dual-Anticancer
      Drug Delivery.
AB  - Functional block copolymers based on poly(2-oxazoline)s are versatile building
      blocks for the fabrication of dual-drug delivery nanoparticles (NPs) for
      anticancer chemotherapy. Core-shell NPs are fabricated from diblock copolymers
      featuring a long and hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) block coupled
      to a relatively short and functionalizable poly(2-methylsuccinate-2-oxazoline)
      (PMestOXA) segment. The PMOXA block stabilizes the NP dispersions, whereas the
      PMestOXA segment is used to conjugate pterostilbene, a natural bioactive phenolic
      compound that is used as lipophilic model-drug and constitutes the hydrophobic
      core of the designed NPs. Subsequent loading of the NPs with clofazimine (CFZ),
      an inhibitor of the multidrug resistance pumps typically expressed in a large
      variety of cancer cells, provides an additional function to their formulation.
      Optimization of the copolymer composition allows the design of polymer scaffolds
      showing low toxicity and capable of assembling into highly stable NPs dispersions
      at physiologically relevant pH. In addition, the incorporation of CFZ increases
      the stability of the NPs and stimulates their internalization by RAW 264.7 cells.

PMID- 29216714
TI  - Fabrication of Hyperbranched Block-Statistical Copolymer-Based Prodrug with Dual
      Sensitivities for Controlled Release.
AB  - Dendrimer with hyperbranched structure and multivalent surface is regarded as one
      of the most promising candidates close to the ideal drug delivery systems, but
      the clinical translation and scale-up production of dendrimer has been hampered
      significantly by the synthetic difficulties. Therefore, there is considerable
      scope for the development of novel hyperbranched polymer that can not only
      address the drawbacks of dendrimer but maintain its advantages. The reversible
      addition-fragmentation chain transfer self-condensing vinyl polymerization (RAFT
      SCVP) technique has enabled facile preparation of segmented hyperbranched polymer
      (SHP) by using chain transfer monomer (CTM)-based double-head agent during the
      past decade. Meanwhile, the design and development of block-statistical
      copolymers has been proven in our recent studies to be a simple yet effective way
      to address the extracellular stability vs intracellular high delivery efficacy
      dilemma. To integrate the advantages of both hyperbranched and block-statistical
      structures, we herein reported the fabrication of hyperbranched block-statistical
      copolymer-based prodrug with pH and reduction dual sensitivities using RAFT-SCVP
      and post-polymerization click coupling. The external homo oligo(ethylene glycol
      methyl ether methacrylate) (OEGMA) block provides sufficient extracellularly
      colloidal stability for the nanocarriers by steric hindrance, and the interior
      OEGMA units incorporated by the statistical copolymerization promote
      intracellular drug release by facilitating the permeation of GSH and H+ for the
      cleavage of the reduction-responsive disulfide bond and pH-liable carbonate link
      as well as weakening the hydrophobic encapsulation of drug molecules. The
      delivery efficacy of the target hyperbranched block-statistical copolymer-based
      prodrug was evaluated in terms of in vitro drug release and cytotoxicity studies,
      which confirms both acidic pH and reduction-triggered drug release for inhibiting
      proliferation of HeLa cells. Interestingly, the simultaneous application of both
      acidic pH and GSH triggers promoted significantly the cleavage and release of CPT
      compared to the exertion of single trigger. This study thus developed a facile
      approach toward hyperbranched polymer-based prodrugs with high therapeutic
      efficacy for anticancer drug delivery.

PMID- 29216715
TI  - How Strong Is the Hydrogen Bond in Hybrid Perovskites?
AB  - Hybrid organic-inorganic perovskites represent a special class of metal-organic
      framework where a molecular cation is encased in an anionic cage. The molecule
      cage interaction influences phase stability, phase transformations, and the
      molecular dynamics. We examine the hydrogen bonding in four AmBX3 formate
      perovskites: [Am]Zn(HCOO)3, with Am+ = hydrazinium (NH2NH3+), guanidinium
      (C(NH2)3+), dimethylammonium (CH3)2NH2+, and azetidinium (CH2)3NH2+. We develop a
      scheme to quantify the strength of hydrogen bonding in these systems from first
      principles, which separates the electrostatic interactions between the amine
      (Am+) and the BX3- cage. The hydrogen-bonding strengths of formate perovskites
      range from 0.36 to 1.40 eV/cation (8-32 kcalmol-1). Complementary solid-state
      nuclear magnetic resonance spectroscopy confirms that strong hydrogen bonding
      hinders cation mobility. Application of the procedure to hybrid lead halide
      perovskites (X = Cl, Br, I, Am+ = CH3NH3+, CH(NH2)2+) shows that these compounds
      have significantly weaker hydrogen-bonding energies of 0.09 to 0.27 eV/cation (2
      6 kcalmol-1), correlating with lower order-disorder transition temperatures.

PMID- 29216716
TI  - Cyclodipeptide c(Orn-Pro) Conjugate with 4-Ethylpiperic Acid Abrogates Cancer
      Cell Metastasis through Modulating MDM2.
AB  - The present work describes the synthesis, characterization, and anticancer
      properties of c(Lys-Pro), P1; c(Orn-Pro), P2; and conjugates PA-c(Lys-Pro), C1;
      PA-c(Orn-Pro), C2; EPA-c(Lys-Pro), C3; and EPA-c(Orn-Pro), C4. Among all,
      conjugate C4 displays potent anticancer activity with IC50 1.3 MUM in MDA-MB-231,
      3.5 MUM in PC-3, 8.9 MUM in MCF-7, and 9.6 MUM in Miapaca-2 cancer cells. In
      addition, C4 downregulates the expression of MDM2 and abrogates the cancer cell
      invasion/metastasis. Through knock-down of MDM2, we demonstrate that this
      abrogation of metastasis by C4 is primarily MDM2 dependent. Furthermore, the
      animal studies underscore the antitumor as well as antimetastatic potential of C4
      in vivo in breast cancer model at a safe and tolerable dose of 20 mg/kg.

PMID- 29216717
TI  - Assembly of High-Potency Photosensitizer-Antibody Conjugates through Application
      of Dendron Multiplier Technology.
AB  - Exploitation of photosensitizers as payloads for antibody-based anticancer
      therapeutics offers a novel alternative to the small pool of commonly utilized
      cytotoxins. However, existing bioconjugation methodologies are incompatible with
      the requirement of increased antibody loading without compromising antibody
      function, stability, or homogeneity. Herein, we describe the first application of
      dendritic multiplier groups to allow the loading of more than 4 porphyrins to a
      full IgG antibody in a site-specific and highly homogeneous manner. Photophysical
      evaluation of UV-visible absorbance and singlet oxygen quantum yields highlighted
      porphyrin-dendron 14 as the best candidate for bioconjugation; with subsequent
      bioconjugation producing a HER2-targeted therapeutic with average loading ratios
      of 15.4:1. In vitro evaluation of conjugate 18 demonstrated a nanomolar
      photocytotoxic effect in a target cell line, which overexpresses HER2, with no
      observed photocytotoxicity at the same concentration in a control cell line which
      expresses native HER2 levels, or in the absence of irradiation with visible
      light.

PMID- 29216718
TI  - The Intramolecular Hydrogen Bond N-H...S in 2,2'-Diaminodiphenyl Disulfide:
      Experimental and Computational Thermochemistry.
AB  - The intramolecular hydrogen bond of the N-H...S type has been investigated
      sparingly by thermochemical and computational methods. In order to study this
      interaction, the standard molar enthalpies of formation in gaseous phase of
      diphenyl disulfide, 2,2'-diaminodiphenyl disulfide and 4,4'-diaminodiphenyl
      disulfide at T = 298.15 K were determined by experimental thermochemical methods
      and computational calculations. The experimental enthalpies of formation in gas
      phase were obtained from enthalpies of formation in crystalline phase and
      enthalpies of sublimation. Enthalpies of formation in crystalline phase were
      obtained using rotatory bomb combustion calorimetry. By thermogravimetry,
      enthalpies of vaporization were obtained, and by combining them with enthalpies
      of fusion, the enthalpies of sublimation were calculated. The Gaussian-4
      procedure and the atomization method were applied to obtain enthalpies of
      formation in gas-phase of the compounds under study. Theoretical and experimental
      values are in good agreement. Through natural bond orbital (NBO) analysis and a
      topological analysis of the electronic density, the intramolecular hydrogen
      bridge (N-H...S) in the 2,2'-diaminodiphenyl disulfide was confirmed. Finally, an
      enthalpic difference of 11.8 kJ.mol-1 between the 2,2'-diaminodiphenyl disulfide
      and 4,4'-diaminodiphenyl disulfide was found, which is attributed to the
      intramolecular N-H...S interaction.

PMID- 29216719
TI  - Prevalent placement error of deep brain stimulation electrode in movement
      disorders (technical considerations).
AB  - BACKGROUND: Deep brain stimulation is an effective and safe technique.
      Displacement of the electrode relative to the optimal stimulation site can lead
      to insufficient effect and sometimes to the need of operative electrode re
      position. OBJECTIVE: This study was aimed to analyse targeting accuracy of deep
      brain stimulation electrode implantation to subthalamic nucleus (STN) and globus
      pallidus internus (Gpi). It detected possible causes of inaccuracy and prevalent
      shift to certain direction. METHODS: Targeting accuracy was analysed in 47
      patients with Parkinson's disease (PD) and 11 patients with dystonia with
      bilateral implantation of deep brain stimulation electrodes between years 2009
      and 2016. RESULTS: A shift of electrode to prevalent direction was observed on
      the left side to medial and posterior and on the right side to lateral direction.
      Greater shift was observed on the left side and in a higher angulation of
      trajectory laterally. Movement of the electrode, because of its traction in
      anchoring device, was identified as a possible factor for prevalent electrode
      shift. Calibration of stereotactic coordinates to correct prevalent shift was
      used. CONCLUSION: Targeting inaccuracy is the result of accumulation of errors in
      individual steps of electrode implantation. Direction of the shift can be random
      or it can be toward a prevalent direction. A correction of prevalent error can
      prevent a suboptimal electrode placement (Tab. 3, Fig. 11, Ref. 29).

PMID- 29216720
TI  - Testosterone replacement therapy (TRT) and its effect on bone marrow. How serious
      is it and is there a true polyglobulia?
AB  - INTRODUCTION: TRT in men with testosterone deficiency syndrome (TDS) had multiple
      positive effects and restore a quality of life of affected men. Polyglobulia is
      the most common dose-limiting adverse effect of TRT, but the mechanisms of TRT
      mediated erythropoesis remain unclear. In this study, we evaluated long term
      haematological side effects of TRT: polyglobulia, elevated hemoglobin (Hb) and
      haematocrit (Ht). METHODS: In a cross-sectional descriptive study, the authors
      treated 69 men with TDS and the average age 59 years and the follow-up period
      81.32 months. The men were treated with three-month i.m. injections of 1000 mg
      testosterone undecanoate. The elevated values were: Hb above 176 g/l, Ht above
      0.52 and erythrocytes (Ery) above 6.0 mil/mcl. RESULTS: 21 out of 69 patients
      (30.43 %) had an increased Hb, Ht or Ery during treatment. The interesting fact
      was that only five men (7.24 %) had increased the number of Ery (true
      polyglobulia). No men with elevated level of Hb, Ht or Ery had other side effects
      (like thrombosis). CONCLUSION: It is still not clear, why in some men on TRT the
      feedback does not work and bone marrow production of red blood cells continues
      even if the upper limit is reached. Authors expect that only 7% of men had true
      polyglobulia, other men had elevated Hb or Ht. Based on our own experience we
      recommend a regular check of men on TRT on order to avoid possible serious side
      effects (Tab. 1, Fig. 2, Ref. 25).

PMID- 29216721
TI  - Alpha-2-macroglobulin and hyaluronic acid as fibromarkers in patients with
      chronic hepatitis C.
AB  - BACKGROUND: Liver fibrosis is the final common pathway of chronic liver diseases
      of various etiology. From the practical standpoint, it would be ideal to have a
      noninvasive fibromarker. The aim of our study was to investigate the levels of
      alpha-2-macroglobulin, potential fibromarker, in correlation to histological
      staging and another potential fibromarker, hyaluronic acid, in patients with
      chronic hepatitis C. METHODS: Population groups in this study consisted of 51
      healthy volunteers and 54 patients with chronic hepatitis C. Liver biopsies were
      obtained under ultrasound guidance. Alpha-2-macroglobulin was determined by
      electroimmunodiffusion and hyaluronic acid with enzyme-linked binding protein
      assay. RESULTS: Both potential fibromarkers, alpha-2-macroglobulin and hyaluronic
      acid, were increased in patients with chronic hepatitis C. The alpha-2
      macroglobulin levels were not significantly increased in the groups F0-F1. In the
      groups F2-F4, alpha-2-macroglobulin levels were significantly higher than in the
      control group. The changes of hyaluronic acid were similar to changes of alpha-2
      macroglobulin. Regression analysis showed a significant correlation between
      hyaluronic acid and alpha-2-macroglobulin levels. CONCLUSIONS: According to the
      results of our study, it can be concluded that alpha-2-macroglobulin and
      hyaluronic acid might be useful markers of liver fibrosis (Tab. 2, Ref. 15).

PMID- 29216722
TI  - The influence of orthodontic non-extraction treatment on the change in the
      inclination and position of incisors in the Europoid race.
AB  - AIM: To detect post-treatment change in the inclination and position of incisors
      in cases treated with orthodontic non- extraction therapy. MATERIALS AND METHODS:
      The group consisted of 102 patients without extractions in lower and upper dental
      arch during orthodontic treatment. Cephalogram examination evaluated the position
      of the lower incisor to point A by Downs-pogonion line (-1 to APo) and
      inclination of the lower incisor to mandibular line (-1 to ML), position of the
      upper incisor to nasion-pogonion line (+1 to NPo), inclination of the upper
      incisor to nasion-sella line (+1 to NS) and the size of the inter-incisival angle
      between upper and central lower incisor (-1 to +1). RESULTS: In 58 % of cases,
      the difference in post-treatment and pre-treatment changes in the position of the
      (-1 to Apo) was within +/- 2 mm, which we considered stable. Statistically
      significantly higher values after treatment were in unstable rather than in
      stable cases with values (-1 to Apo), (-1 to ML), (+1 to NPo). Statistically
      significantly lower value after the treatment was measured in unstable cases
      rather than in stable cases with a value (-1 to +1). There was no statistically
      significantly different value in stable and unstable cases after treatment in
      values (+1 to NS). CONCLUSION: The number of stable post-treatment cases was only
      16 % higher than the number of unstable cases. With the increasing value (-1 to
      Apo), the value (-1 to ML) and (+1 to NPo) increased, the value (+1 to -1)
      decreased. The value (-1 to NS) not after treatment was not statistically
      significantly different in stable and unstable cases (Tab. 6, Fig. 4, Ref. 27).

PMID- 29216723
TI  - Effect of aquaporin 1 and 4 on masticatory muscles degeneration as a result of
      aging.
AB  - OBJECTIVE: The changes in the mouth structures due to aging cause some structural
      and functional changes by affecting masticatory muscles over time. The aim of
      this study was to evaluate the aging-related histopathologic changes and
      immunohistochemically assessed aquaporin 1 and 4 expressions on masseter and
      temporal muscles. MATERIAL AND METHODS: 14 Balb/c white mice (50-80 g) were used
      in this study. Group I consisted of young animals (2-month-individuals) (n = 7)
      and Group II consisted of older animals (18-month-old) (n = 7). After routine
      histological follow-ups were made, tissues were stained immunohistochemically for
      aquaporin 1 and aquaporin 4 as well as with hematoxylin-eosin. RESULTS: It was
      seen that while the masseter and temporalis muscle tissues showed a high
      immunoreactivity (+++) for aquaporin 1 and 4 in young mice, they showed a weak
      immunoreactivity (+) for aquaporin 1 and 4 in old mice (p = 0.001). In the H
      score assessment, aquaporin 1 and 4 immunoreactivity was significantly higher in
      young mice than in old mice (p = 0.002). CONCLUSIONS: Consequently, it was shown
      that degeneration of the masticatory muscles increased with aging and there was a
      decrease in intra- and intercellular exchange of substances because of changing
      aquaporin 1 and aquaporin 4 expressions (Tab. 2, Fig. 4, Ref. 20).

PMID- 29216724
TI  - Inhibition by Egb761 of the effect of cellphone radiation on the male
      reproductive system.
AB  - OBJECTIVES: To determine the effects of Egb761 on testicular tissues and semen
      parameters in rats exposed to cellphone waves. BACKGROUND: EGb761 has antioxidant
      properties as a free-radical scavenger. Cellphone electromagnetic radiation (EMR)
      induces oxidative stress in cells. METHODS: Twenty-one Wistar albino male adult
      rats were divided into three groups (control, experimental, treatment), including
      seven rats in each. The experimental and treatment groups were exposed to
      cellphone EMR (0.96 W/kg) for six weeks (4 hrs/day). Egb761 (100 mg/kg/day) was
      also added to the treatment. Testes, epididymal semen and blood plasma were used
      for analysis. RESULTS: Exposure to cellular phone radiation resulted in a
      significant impairment in testicular morphometry and histological structure,
      reduction of total and motile sperm numbers and plasma testosterone level. Egb761
      administration improved testicular damage and led to a marked increase in plasma
      testosterone levels and total and motile sperm numbers. CONCLUSION: Male
      reproductive system is susceptible to cellphone radiation. Cellphone waves induce
      toxic effects in testicular tissues, impair spermatogenesis and cause an
      imbalance in testosterone hormone levels. Egb761 ameliorated these toxic effects
      by reversing testicular tissue damage, restoring normal spermatogenesis and
      hormone levels. This suggests that Egb761 is a potential therapeutic agent
      against EMR-induced male reproductive toxicity (Tab. 3, Fig. 6, Ref. 45).

PMID- 29216725
TI  - Decreased circulatory microRNA-4478 as a specific biomarker for diagnosing non-ST
      segment elevation myocardial infarction (NSTEMI) and its association with soluble
      leptin receptor.
AB  - OBJECTIVE: This study aimed to assess the usefulness of circulatory microRNA-4478
      (miR-4478) and soluble leptin receptor (sLEPR) in prognosis and diagnosis of non
      ST-segment elevation myocardial infarction (NSTEMI) and to introduce miR-4478 as
      a new biomarker for NSTEMI disease. This study aimed also to examine correlation
      between miR-4478 and soluble leptin receptor and effects of miR-4478 on leptin
      receptor concentration. BACKGROUND: MicroRNAs could be used as predictive
      biomarkers for diseases. METHODS: We collected sera of 80 angiographically
      confirmed NSTEMI patients and 80 healthy individuals and performed RNA
      extraction, cDNA synthesis, measurement of microRNAs, sLEPR and other
      chemistries. Statistical analyses were done using excel, XLSAT, and SPSS. Quality
      control analysis was done triplicated for 7 serial dilution of stock cDNA
      solution. RESULTS: The patients with NSTEMI had higher serum levels of miR-4478,
      sLEPR, cTnI, CKMB, Urea, creatinine, glucose, cholesterol, TG, and ALP but lower
      levels of ALT compared with the normal healthy individuals. We detected decrease
      in expression of miR-4478 (2^-??Cq = 0.161 +/- 0.211) along with increase in
      sLEPR levels (F = 3.645, p < 0.001) in the NSTEMI group compared with normal
      individuals. Pearson's correlation tests indicated positive correlation of miR
      4478 and sLEPR (p < 0.001, R2 = 0.698). There was sensitivity and specificity of
      87.5% and 98.8% for miR-4478 and 92.5% and 87.5% for sLEPR. CONCLUSION:
      Circulatory miR-4478 and sLEPR may be used as predictors of NSTEMI. miR-4478 may
      also be used as a new biomarker for NSTEMI disease (Tab. 3, Fig. 6, Ref. 30).

PMID- 29216726
TI  - High serum levels of IGF-I and IGFBP3 may increase comorbidity risk for asthmatic
      patients.
AB  - OBJECTIVE: Asthma is known as a chronic inflammatory lung disease which has also
      systemic features. Insulin-like growth factor I (IGF-I) plays a role for asthma
      pathogenesis. Controversially, IGF-binding protein 3 (IGFBP3) blocks asthma
      development. That is why IGF-I and IGFBP3 are targeted for future therapeutic
      treatments of asthma. We aimed to investigate serum level of IGF-I and IGFBP3 in
      patients with asthma. This study was performed in 27 asthma and 23 healthy
      individuals. Serum levels of IGF-I and IGFBP3 were measured by human ELISA assay
      kits. Serum levels of IGF-I and IGFBP3 were significanlty higher in the asthma
      group than the control group. Significant negative correlation was found between
      IGF-I and asthma control test (ACT) puan, O2 saturation, Forced Expiratory Volume
      in 1 second/ Forced Vital Capacity (FEV1/FVC), Forced Expiratory Flow 25
      second/75 second (FEF2575) (%). Significant positive correlation was found
      between IGFBP3 and IGF-I, systolic blood pressure. Significant negative
      correlation was found between IGF-I and FEV1 (ml). RESULTS: Our results indicate
      that the serum levels of IGF-I and IGFBP3 are significanlty elevated in the
      asthma group. We assume that current treatment strategies are not really good
      enough for asthma. We suppose further strategies which are seeking to balance IGF
      I and IGFBP3 should be developed for more effective and curative treatment of
      asthma (Tab. 2, Fig. 2, Ref. 22).

PMID- 29216727
TI  - Effect of EGF on Bax, Bcl-2 and Fas expression in ulcerous disease and N87 cell
      line.
AB  - BACKGROUND: To evaluate the effect of epithelial growth factor (EGF) in primary
      culture of ulcer patients and N87 cell line on expressions of apoptotic genes.
      METHODS: Ulcer patients who attended Gastroenterology Clinic of Mersin University
      Medical Faculty were included in this study. Three different doses of EGF were
      applied to the primary culture of biopsy samples from ulcer patients and gastric
      cancer cell-line (ATCC-NCI-N87) . The expression levels of Bax, Bcl-2 and Fas
      genes were measured with quantitative real-time PCR (qRT-PCR). RESULTS:
      DeltaDeltaCT analysis with qRT-PCR revealed no significant change in gene
      expression of Bax, Bcl-2 or Fas within the ulcer, normal tissue and gastric
      cancer. No significant change was determined between Bax and Bcl-2 gene
      expression levels and applied EGF doses when groups were compared for each EGF
      dose. On the other hand, when 50 ng/ul of EGF was administered, Fas mRNA
      expression level was significantly lower in the gastric cancer cell line compared
      to patients with ulcer and normal gastroduodenal tissue (p<0.05). CONCLUSION: In
      this study which was done with a restricted patient group, our results revealed
      that apoptosis induced by Fas expression in gastroduodenal suppressing
      carcinogenesis process plays an active role in gaining anti-apoptotic properties
      of cells (Tab. 4, Fig. 2, Ref. 27).

PMID- 29216728
TI  - Optimization of Eva Green real-time mPCR for differentiating C. jejuni/coli
      directly from feces.
AB  - OBJECTIVE: To develop and optimize a rapid molecular method for diagnosing
      campylobacteriosis directly from a clinical fecal sample and at the same time for
      determining the most common causing agents - C. jejuni/coli. MATERIALS AND
      METHODS: 38 clinical fecal samples from hospitalized patients with diarrheal
      syndrome were tested using a rapid immunochromatographic test. All positive
      samples were tested for confirmation by culturing in a microaerophilic
      atmosphere. The Eva Green real-time mPCR reaction of a direct fecal sample was
      conducted using the "IQ5TM Real-Time PCR System" apparatus. RESULTS: Out of 38
      clinical fecal samples which were ICT positive, 18 strains were isolated by
      culture, namely, 17 of C. jejuni and 1 of C. coli. The Eva Green real-time mPCR
      reaction also reported 18 positive samples for Campylobacter, out of which 17
      were of C. jejuni and only one of C.coli. CONCLUSION: We developed and optimized
      the Eva Green real-time mPCR for the detection and species differentiation of C.
      jejuni/coli directly from a clinical fecal sample. The molecular analysis we
      described has a 100% sensitivity and specificity when comparing the results
      obtained by it to those of the culture method, which is currently the "gold
      standard" in the diagnosis of campylobacteriosis (Tab. 2, Fig. 1, Ref. 6).

PMID- 29216730
TI  - The influence of cranio-cervical rehabilitation in patients with myofascial
      temporomandibular pain disorders.
AB  - OBJECTIVE: The aim of the study was to prove the causality between the
      craniocervical dysfunction and myofascial pain in the head and neck and to
      demonstrate the clinical value and usefulness of physiotherapy as one of the
      therapeutic options for myofascial pain. METHODS: The group of patients diagnosed
      with myofascial dysfunctional pain syndrome contained 98 patients out of which 79
      patients (81 %) were females and 19 patients (19 %) were males. The majority of
      the patients were aged between 26 and 35 years; the total age range was 14-77
      years with the average of 38 years. Observed patients were subdivided into three
      groups. Standard therapeutic methods aimed at the temporomandibular joint were
      provided to the patients of the first group. The second group of the patients
      received therapy aimed at cervical muscles only. Complex rehabilitation was
      applied in the third group of patients. The most frequent method used in the
      evaluation of chronic musculoskeletal pain in clinical studies is the visual
      analogue scale (VAS). RESULTS: According to our results, all three groups of
      patients saw an improvement in pain perception, but the overall subjective
      remission of painful sensations in the third group took place in as many as 88 %
      of patients. In this group, there was a significant decrease in the tenderness of
      trigger points in the trapezius and sternocleidomastoid muscles. CONCLUSION: It
      was proved that a combination of simple relaxing and stretching exercises of
      cervical muscles with a standard method used in the therapy of masticatory
      muscles is significantly more efficient (Fig. 5, Ref. 18).

PMID- 29216729
TI  - Periostin normalizes levels of cardiac markers in rats with experimental
      isoproterenol cardiotoxicity.
AB  - BACKGROUND: Although the molecular mechanism of cardiac healing is not fully
      understood, myocardial infarction is one of the most usual diagnoses in
      hospitalized patients in industrialized nations while periostin has been recently
      suggested to have a potential in tissue repairing following myocardial ischemia.
      OBJECTIVES: To investigate the effects of periostin on the levels of selected
      cardiac parameters (cardiac troponin I and T, creatine kinase and creatine kinase
      isoenzyme-MB), antioxidant/lipid peroxidation parameters (superoxide dismutase,
      catalase, and malondialdehyde), hepatic parameters (alkaline phosphatase, lactate
      dehydrogenase, aspartate and alanine transaminases) as well as lipids (total
      cholesterol, triglyceride, high, low and very-low-density lipoproteins) in a rat
      model of isoproterenol---induced myocardial injury. METHODS: A total of 84 male
      rats were grouped into saline (Group I), periostin (Group II), isoproterenol
      (Group III) and isoproterenol+periostin (Group IV) groups (n = 21). Isoproterenol
      (85 mg/kg/day) and periostin groups were both injected intraperitoneally (1
      MUg/kg). RESULTS: Our results revealed that periostin has a positive reducing
      effect on the levels of analysed parameters especially on cardiac troponins and
      creatine kinases on days 7 and 28 of the recovery period following the induced
      experimental heart damage in rats. CONCLUSION: It is concluded that periostin
      could have a potential to increase the rate of myocardial recovery after
      myocardial infarction (Tab. 5, Ref. 28).

PMID- 29216733
TI  - Should the Australian Therapeutic Goods Administration recommend rapid dosing of
      lithium carbonate in acute mania?

PMID- 29216731
TI  - Preclinical Testing of a Combination Stone Basket and Ureteral Balloon to Extract
      Ureteral Stones.
AB  - We have developed the Peralta Stone Extraction System to increase the safety of
      ureteral stone extraction. The device combines a nitinol stone basket and low
      pressure balloon into a single device. After visualization, the stone is captured
      in the tipless nitinol basket and enveloped by a low-pressure balloon. We tested
      the performance of device prototypes in a porcine model using stone mimics with
      diameters ranging from 4.2 to 6.2 mm. Stones extracted with the device required
      less force when compared with stones in a standard ureteral stone basket. The
      force reduction was most pronounced for stones greater than 4.2 mm in diameter,
      and when traversing a ureteral stenosis model. In conclusion, a combination stone
      basket and balloon device may provide a new and safer way to extract ureteral
      stones.

PMID- 29216734
TI  - Paediatric bipolar disorder: Reality or myth?

PMID- 29216732
TI  - Vitamin B12 sources and microbial interaction.
AB  - Vitamin B12 is synthesized only by certain bacteria and archaeon, but not by
      plants. The synthesized vitamin B12 is transferred and accumulates in animal
      tissues, which can occur in certain plant and mushroom species through microbial
      interaction. In particular, the meat and milk of herbivorous ruminant animals
      (e.g. cattle and sheep) are good sources of vitamin B12 for humans. Ruminants
      acquire vitamin B12, which is considered an essential nutrient, through a
      symbiotic relationship with the bacteria present in their stomachs. In aquatic
      environments, most phytoplankton acquire vitamin B12 through a symbiotic
      relationship with bacteria, and they become food for larval fish and bivalves.
      Edible plants and mushrooms rarely contain a considerable amount of vitamin B12,
      mainly due to concomitant bacteria in soil and/or their aerial surfaces. Thus,
      humans acquire vitamin B12 formed by microbial interaction via mainly ruminants
      and fish (or shellfish) as food sources. In this review, up-to-date information
      on vitamin B12 sources and bioavailability are also discussed. Impact statement
      To prevent vitamin B12 (B12) deficiency in high-risk populations such as
      vegetarians and elderly subjects, it is necessary to identify foods that contain
      high levels of B12. B12 is synthesized by only certain bacteria and archaeon, but
      not by plants or animals. The synthesized B12 is transferred and accumulated in
      animal tissues, even in certain plant tissues via microbial interaction. Meats
      and milks of herbivorous ruminant animals are good sources of B12 for humans.
      Ruminants acquire the essential B12 through a symbiotic relationship with
      bacteria inside the body. Thus, we also depend on B12-producing bacteria located
      in ruminant stomachs. While edible plants and mushrooms rarely contain a
      considerable amount of B12, mainly due to concomitant bacteria in soil and/or
      their aerial surfaces. In this mini-review, we described up-to-date information
      on B12 sources and bioavailability with reference to the interaction of microbes
      as B12-producers.

PMID- 29216735
TI  - The psychological impact of epilepsy across different developmental stages: An
      Eriksonian formulation.

PMID- 29216736
TI  - The challenges and benefits of conducting linked epidemiological and
      neurobiological health surveillance into the impacts of military deployment in
      Australia.

PMID- 29216737
TI  - Electroconvulsive therapy in an elderly patient with recurrent meningiomas.

PMID- 29216738
TI  - Medical Assistance in Dying and Mental Health: A Legal, Ethical, and Clinical
      Analysis.
AB  - Medical assistance in dying (MAiD) legislation is now over a year old in Canada,
      and consideration is turning to whether MAiD should be extended to include
      serious mental illness as the sole qualifying condition for being eligible for
      MAiD. This article considers this question from ethical and clinical
      perspectives. It argues that extending the eligibility for MAiD to include those
      with a serious mental illness as the sole eligibility criterion is not ethical,
      necessary, or supported current psychiatric practice or opinion.

PMID- 29216739
TI  - Lymphatic drainage efficiency: a new parameter of lymphatic function.
AB  - Background Following convection from blood capillaries, plasma proteins are
      transported to loco-regional lymph nodes in two stages: first, uptake into
      peripheral lymphatics, and second, transport to nodes. Purpose To introduce a new
      parameter of lymphatic function that quantifies stage 2 - lymphatic drainage
      efficiency (LDE). Material and Methods Percentage injected activity (IIQ) in ilio
      inguinal nodes 150 min following subcutaneous foot web-space injection of Tc-99 m
      nanocolloid was measured in 102 patients undergoing lymphoscintigraphy using a
      method in which a standard is placed by image guidance over the nodes. Percentage
      activity leaving the injection depot by 150 min ( k) was measured in 60/102
      patients. LDE (%) = 100 * (IIQ/ k). Abnormal lymphoscintigraphy was defined
      qualitatively as: (i) no activity in ilio-inguinal nodes at 45 min or negligible
      activity at 150 min (delay); (ii) lymph diversion through skin and/or deep
      system; and (iii) focal tracer accumulation suggesting cellulitis. Results
      Scintigraphy was bilaterally normal in 82 limbs, unilaterally normal in 40 limbs
      and abnormal in 82 limbs. IIQ correlated with k in bilaterally normal (r = 0.86;
      n = 52), unilaterally normal (r = 0.67; n = 27), and abnormal (r = 0.82; n = 41)
      limbs. IIQ, k, and LDE were significantly lower in unilaterally normal (9.3 +/-
      5.4%, 13.8 +/- 7.1%, and 65 +/- 30%) compared with bilaterally normal limbs (15.4
      +/- 8.4% [ P > 0.0001], 18.3 +/- 8.9% [ P = 0.025], and 84 +/- 30% [ P = 0.01]).
      LDE was lower in limbs displaying skin diversion and/or delay. Conclusion LDE is
      a new quantitative index that has potential value in clinical research but
      requires further clinical evaluation. Abnormal quantitative indices indicate that
      limbs unilaterally normal on lymphoscintigraphy are not functionally normal.

PMID- 29216740
TI  - New concepts of radiologic preoperative evaluation of anterior shoulder
      instability: on-track and off-track lesions.
AB  - The shoulder is the most frequently dislocated joint in the body due to a larger
      range of motion and a small area of articulation between the humeral and glenoid
      surfaces. Traumatic shoulder dislocations, especially those associated with
      injury to the labroligamentous or bony stabilizers of the joint, lead to further
      reduction of articular surface contact with resultant glenohumeral instability
      and recurrent shoulder dislocations. Imaging plays an increasingly important role
      in the preoperative evaluation of patients with traumatic shoulder instability by
      evaluating glenohumeral bone loss (uni- or bipolar), assessing soft tissue
      injuries and identifying patients at risk of postoperative recurrence.
      Quantification of bone loss is key to differentiate engaging vs. non-engaging
      Hill-Sachs lesions, while newer concepts of "on-track" vs. "off-track" lesions
      are being discussed that can determine the required surgical approaches. In this
      article, we review the preoperative imaging approaches, traditional treatments,
      outline the bone loss measurement strategies and review these new tracking
      concepts with relevant case examples.

PMID- 29216741
TI  - Evaluation of cellulose pads as a method to detect cytomegalovirus DNA in
      neonatal urine.
AB  - Background Several approaches exist to screen neonates for congenital
      cytomegalovirus infection. We here describe a new method using cellulose pads for
      urine collection and its evaluation in an experimental and a clinical setting.
      Methods We systematically tested the effect of storage duration of the pads after
      exposure to cytomegalovirus-positive urine, meconium contamination and specimen
      handling on the cytomegalovirus load and the detection rate. Further, the method
      was tested in clinical practice in a cohort of 500 neonates. Results Following
      exposure of urine pads with cytomegalovirus-positive urine, the viral load
      decreased after 15 min, 12 h, 24 h, and 7 days to 63.2%, 42.1%, 31.6%, and 9.3%
      of the baseline value. Cytomegalovirus detection rate after seven days was 100%.
      Contamination with meconium resulted in a comparable reduction of the viral load.
      The detection rate for dried urine pads after seven days was 93.3%. In clinical
      practice, urine collection from pads was successful in 73.6% by the first attempt
      and in 26.4% by the second attempt. Conclusions Urine collection using cellulose
      pads seems feasible regardless of a reduction of the cytomegalovirus load due to
      exposure to the pad itself or to meconium. Drying of the exposed urine pad should
      be avoided.

PMID- 29216742
TI  - Redox-sensing iron-sulfur cluster regulators.
AB  - SIGNIFICANCE: Iron-sulfur cluster proteins carry out a wide range of functions,
      including as regulators of gene transcription/translation in response to
      environmental stimuli. In all known cases, the cluster acts as the sensory
      module, where the inherent reactivity/fragility of iron-sulfur clusters towards
      small/redox active molecules is exploited to effect conformational changes that
      modulate binding to DNA regulatory sequences. This promotes an often substantial
      re-programming of the cellular proteome that enables the organism or cell to
      adapt to, or counteract, its changing circumstances. Recent Advances. Significant
      progress has been made recently in the structural and mechanistic
      characterization of iron-sulfur cluster regulators and, in particular, the O2 and
      NO sensor FNR, the NO sensor NsrR, and WhiB-like proteins of Actinobacteria.
      These are the main focus of this review. CRITICAL ISSUES: Striking examples of
      how the local environment controls the cluster sensitivity and reactivity are now
      emerging, but the basis for this is not yet fully understood for any regulatory
      family. FUTURE DIRECTIONS: Characterization of iron-sulfur cluster regulators has
      long been hampered by a lack of high resolution structural data. Though this
      still presents a major future challenge, recent advances now provide a firm
      foundation for detailed understanding of how a signal is transduced to effect
      gene regulation. This requires the identification of often unstable intermediate
      species, which are difficult to detect and may be hard to distinguish using
      traditional techniques. Novel approaches will be required to solve these
      problems.

PMID- 29216743
TI  - A systematic scoping review and synthesis of dementia and communication theory.
AB  - Aim This review considers the theoretical literature concerning communication
      between a person with dementia and a person without dementia. Methods Theoretical
      accounts of communication between a person with dementia and a person without
      dementia were identified through database searches, hand searching of reference
      lists and contacting experts in the topic area. Results Twenty-one articles were
      included in the final review, yielding 18 different theoretical accounts of
      communication in the context of dementia. Thematic synthesis showed that four
      categories could account for the majority of the material described in these
      theories, even though they were derived from very different perspectives. These
      categories were mutuality, personhood, anxiety reduction and environmental
      considerations. Discussion The four categories identified in the thematic
      synthesis were reminiscent of Kitwood's theory of person-centred dementia care.
      Different interpretations of this finding are considered. Most theoretical
      accounts focused on the relational aspects of communication. This meant that
      societal and individual accounts of communication in the context of dementia were
      relatively impoverished in terms of theory. Conclusions There is widespread
      agreement regarding the important components of good quality communication in the
      context of dementia. This suggests exciting opportunities for collaboration
      between apparently disparate bodies of literature. Individual and societal
      accounts of communication in the context of dementia are relatively neglected and
      would benefit from more research.

PMID- 29216744
TI  - Dose uniformity of budesonide Easyhaler(r) under simulated real-life conditions
      and with low inspiration flow rates.
AB  - Budesonide Easyhaler(r) multidose dry powder inhaler is approved for the
      treatment of asthma. Objectives were to determine the delivered dose (DD)
      uniformity of budesonide Easyhaler(r) in simulated real-world conditions and with
      different inspiration flow rates (IFRs). Three dose delivery studies were
      performed using 100, 200, and 400 ug/dose strengths of budesonide. Dose
      uniformity was assessed during in-use periods of 4-6 months after exposure to
      high temperature (30 degrees C) and humidity (60% relative humidity) and after
      dropping and vibration testing. The influence of various IFRs (31, 43, and 54
      L/min) on the DD was also investigated. Acceptable dose uniformity was declared
      when mean DD were within 80-120% of expected dose; all data reported
      descriptively. DD was constant (range: 93-109% of expected dose) at all in-use
      periods and after exposure to high temperature and humidity for a duration of up
      to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of
      expected dose). Similarly, DD was constant and within 10% of expected dose across
      all IFRs. Results indicate that budesonide Easyhaler(r) delivers consistently
      accurate doses in various real-life conditions. Budesonide Easyhaler(r) can be
      expected to consistently deliver a uniform dose and improve asthma control
      regardless of high temperature and humidity or varying IFR.

PMID- 29216745
TI  - Differential Experimental Effects of a Short Bout of Walking, Meditation, or
      Combination of Walking and Meditation on State Anxiety Among Young Adults.
AB  - INTRODUCTION: Single bouts of aerobic exercise and meditation have been shown to
      improve anxiety states. Yet to be evaluated in the literature, we sought to
      examine the effects of a single, short bout of aerobic exercise or meditation, as
      well as exercise and meditation combined on state anxiety among young adults.
      DESIGN: Randomized controlled trial. SETTING: University. SUBJECTS: Participants
      (N = 110, mean age = 21.4 years) were randomly assigned to walk, meditate, walk
      then meditate, meditate then walk, or to sit (inactive control). MEASURES: All
      walking and meditation bouts were 10 minutes in duration. Participants' state
      anxiety was monitored before and after the intervention using the State Trait
      Anxiety Inventory questionnaire. RESULTS: Significant group * time interaction
      effects were observed ( P = .01). Post hoc paired t tests revealed that state
      anxiety significantly decreased from baseline to postintervention in the
      meditation ( P = .002), meditation then walk ( P = .002), and walk then
      meditation ( P = .03) groups but not the walk ( P = .75) or control ( P = .45)
      groups. CONCLUSION: Meditation (vs a brisk walk) may be a preferred method of
      attenuating anxiety symptomology. Individuals desiring the health benefits
      associated with aerobic exercise may achieve additional anxiolytic benefits if
      they employ a brief meditation session before or after exercising.

PMID- 29216746
TI  - Employing a Fixed-Lean Multiple Schedule in the Treatment of Challenging Behavior
      for Children With Autism Spectrum Disorder.
AB  - Despite its utility, there is limited applied research on employing fixed-lean
      (FL) schedules of reinforcement in treatment packages to address challenging
      behavior. One potential reason is that abrupt shifts to terminal schedules of
      reinforcement have been associated with immediate increases in challenging
      behavior before subsiding to clinically acceptable levels. The purpose of the
      present study was to (a) provide evidence demonstrating the utility of a FL
      multiple schedule (MS) in the treatment of challenging behavior in applied
      settings, (b) examine the potential effects of alternative stimuli on challenging
      behavior during a FL MS, and (c) assess the social validity of this treatment
      package with participants and caregivers. The results of this study showed low
      levels of challenging behavior and discriminated mands during the FL MS, but no
      evidence to support the inclusion of alternative stimuli. In addition, caregivers
      of both participants reported high levels of satisfaction with the treatment
      package. Implications for research and clinical practice are discussed.

PMID- 29216747
TI  - Factor Structure and Further Validation of the 20-Item Short Form of the
      Obsessive Beliefs Questionnaire.
AB  - A 44-item version of the Obsessive Beliefs Questionnaire (OBQ-44) put forward by
      the Obsessive Compulsive Cognitions Working Group remains the most widely used
      version of the OBQ, despite research casting doubt on its factorial validity and
      the existence of a short form (i.e., OBQ-20). In a large sample of undergraduate
      students ( n = 1,210), a bifactor model of the OBQ-20, consisting of a general
      factor and four specific factors (threat, responsibility, importance/control of
      thoughts, perfectionism/certainty), was supported as the best-fitting model. None
      of the examined OBQ-44 models provided adequate fit. The bifactor model of the
      OBQ-20 was retained in two independent samples ( n = 1,342 community adults, n =
      319 undergraduate students). The incremental validity of the specific factors of
      the OBQ-20 beyond the general factor was evidenced across multiple criterion
      indices, including obsessive-compulsive symptom measures and reactions to a
      thought-induction task. Results further support use of the OBQ-20.

PMID- 29216748
TI  - Quality of Care for Patients With Diabetes and Mulitmorbidity Registered at Nurse
      Practitioner-Led Clinics.
AB  - Background Nurse Practitioner-Led Clinics are a new model of primary healthcare
      in Ontario. Nurse Practitioner-Led Clinics are distinctive in that nurse
      practitioners are the primary care providers working with an interprofessional
      team. There have been no evaluations of the quality of care within the Nurse
      Practitioner-Led Clinic model. Purpose Evaluation of the Nurse Practitioner-Led
      Clinic model, specifically for complex clinical presentations, will provide
      insights that may be used to inform improvements to the delivery of care in the
      Nurse Practitioner-Led Clinics. The aim of this study was to evaluate the extent
      to which diabetes care was complete and to determine the impact of organizational
      tools, including electronic medical record tracking, diabetes care template, and
      referral to community programs, on the completeness of care for patients with
      diabetes and multimorbidity at Nurse Practitioner-Led Clinics. Methods An audit
      of 30 charts was conducted at five different Nurse Practitioner-Led Clinics (n =
      150) for patients with diabetes and at least one other chronic condition.
      Indicators included patient and organizational characteristics as well as
      diabetes care items taken from diabetes clinical guidelines. Results Overall,
      care for patients with diabetes and multimorbidity in Nurse Practitioner-Led
      Clinics was complete. However, there were no significant associations between
      patient or organizational characteristics and the extent to which diabetes care
      was complete.

PMID- 29216749
TI  - Impact of Palliative Chemotherapy and Travel Distance on Hospice Referral in
      Patients With Stage IV Pancreatic Cancer: A Retrospective Analysis Within a
      Veterans Administration Medical Center.
AB  - BACKGROUND: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a poor
      prognosis despite chemotherapy advancements. Although hospice utilization has
      increased, timing of referral is not always optimal. AIM: To investigate whether
      palliative chemotherapy and travel distance to the treatment center impact
      hospice referral patterns in veterans of the US military in order to identify
      potential areas for improving referral timing. DESIGN: Demographic and clinical
      data were collected retrospectively according to the timing of hospice referral.
      Settings/Participants: Patients with mPDAC within a Veterans Administration
      Medical Center from 2005 to 2014. RESULTS: Of 58 patients identified, 52 were
      referred to hospice. The median time from diagnosis to referral and referral to
      death was 2.4 and 3.1 weeks, respectively. Palliative chemotherapy was
      administered to 22 (42.3%) patients, with 30 (57.7%) patients not treated due to
      poor functional status (n = 16, 53.3%) or patient refusal (n = 14, 46.7%). Subset
      analysis for those travelling >60 miles versus <60 miles to the treatment center
      showed the median time to hospice referral was 1.7 versus 4.7 weeks. With no
      significant differences between groups, univariate analysis demonstrated that
      those referred to hospice >2.4 weeks from diagnosis more often received
      chemotherapy ( P < .001) and lived <60 miles from the treatment center ( P =
      .05). CONCLUSION: Receipt of palliative chemotherapy and proximity to the
      treatment center appear to delay referral to hospice in patients with mPDAC.
      Increasing physician awareness of such factors that may impact the decision to
      involve hospice is necessary for delivering optimal oncology care.

PMID- 29216750
TI  - PDE/cAMP/Epac/C/EBP-beta Signaling Cascade Regulates Mitochondria Biogenesis of
      Tubular Epithelial Cells in Renal Fibrosis.
AB  - AIMS: Cyclic adenosine 3'5'-monophosphate (cAMP) is a universal second messenger
      that plays an important role in intracellular signal transduction. cAMP is
      synthesized by adenylate cyclases from adenosine triphosphate and terminated by
      the phosphodiesterases (PDEs). In the present study, we investigated the role of
      the cAMP pathway in tubular epithelial cell mitochondrial biogenesis in the
      pathogenesis of renal fibrosis. RESULTS: We found that the cAMP levels were
      decreased in fibrotic kidney tissues, and replenishing cAMP could ameliorate
      tubular atrophy and extracellular matrix deposition. The downregulation of cAMP
      was mainly attributed to the increased PDE4 expression in tubular epithelial
      cells. The inhibition of PDE4 by PDE4 siRNA or the specific inhibitor, rolipram,
      attenuated unilateral ureteral obstruction-induced renal interstitial fibrosis
      and transforming growth factor (TGF)-beta1-stimulated primary tubular epithelial
      cell (PTC) damage. The Epac1/Rap1 pathway contributed to the main effect of cAMP
      on renal fibrosis. Rolipram could restore C/EBP-beta and PGC-1alpha expression
      and protect the mitochondrial function and structure of PTCs under TGF-beta1
      stimulation. The antifibrotic role of rolipram in renal fibrosis relies on C/EBP
      beta and PGC-1alpha expression in tubular epithelial cells. Innovation and
      Conclusion: The results of the present study indicate that cAMP signaling
      regulates the mitochondrial biogenesis of tubular epithelial cells in renal
      fibrosis. Restoring cAMP by the PDE4 inhibitor rolipram may ameliorate renal
      fibrosis by targeting C/EBP-beta/PGC1-alpha and mitochondrial biogenesis.
      Antioxid. Redox Signal. 29, 637-652.

PMID- 29216751
TI  - Decreased viability and proliferation of CHANG conjunctival epithelial cells
      after contact with ultraviolet light-irradiated pollen.
AB  - CONTEXT: Contact with pollen is the major reason for the development of allergic
      symptoms on the ocular surface leading to a significant increase of allergic
      diseases worldwide. Environmental changes such as increased ultraviolet (UV)
      radiation and air pollution are discussed as contributory causes for this
      increase. OBJECTIVE: We investigated the effect of UV light on the histamine
      content of pollen and examined if an irradiation of pollen affects the viability
      and proliferation of conjunctival cells. MATERIALS AND METHODS: Alder (Alnus
      glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time
      periods with sunlight, UV-A or UV-B light and the histamine content was analysed
      and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG
      cells) were exposed to irradiated and non-irradiated pollen followed by an
      assessment of cell viability with the colorimetric MTS test and the impedance
      based measurement of cell proliferation using the xCELLigence real-time analysis
      system. RESULTS: UV light irradiation increased the histamine level of alder and
      hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated
      pollen induced a statistically significant higher decrease of cell viability than
      treatment with non-irradiated pollen. DISCUSSION AND CONCLUSIONS: Our results
      indicate that UV light is able to alter pollen thus making them more harmful for
      conjunctival cells.

PMID- 29216752
TI  - An acryl resin-based swellable microneedles for controlled release intradermal
      delivery of granisetron.
AB  - Swellable microneedles (SMNs) are made of hydrogels and can deliver drug with
      controlled delivery rate by the cross-link density of the hydrogel. In this
      study, an acryl resin-based SMNs was developed for poorly water-soluble drugs.
      The making process of the SMNs is very simple and only need 60 min. The SMNs has
      high mechanical strength and is not easily broken. In-vitro release of SMNs
      loaded model drug, granisetron base (GRB), was investigated. The results showed
      that seven days controlled release of GRB was obtained when SMNs contained pore
      foaming agents (1.5% dicalcium phosphate (CaHPO4) and 1.5% polyvinylpyrrolidone
      (PVP)). The maximum amount delivered into skin was 86.158 +/- 7.82% of the
      initial GRB (2.1 mg) loaded on SMNs preparation. Pharmacokinetics study in rats
      indicated a dose-dependent profile of plasma GRB concentrations and that the
      controlled release of 2.1 mg dose was observed for 144 hours. In conclusion,
      these SMNs provided a potential minimally invasive route for controlled-release
      systemic delivery of poorly water-soluble drugs.

PMID- 29216753
TI  - The Impact of Safety Plans in an Outpatient Clinic.
AB  - BACKGROUND: Safety plans are recommended as tools to mitigate suicide risk;
      however, their effectiveness remains unclear. AIM: To evaluate the impact of
      safety plans on patient care at an outpatient mental health clinic. METHOD: In
      this retrospective chart review, patients' treatment engagement, health-care
      utilization, and risk behaviors were measured. Patients served as their own
      historical controls, and we compared outcomes in the 6 months before and 6 months
      after creation of safety plans. RESULTS: In all, 48 patient charts were
      identified. Hospitalizations were significantly reduced and use of crisis calls
      significantly increased after implementation of safety plans. There were five
      suicide attempts before safety plan completion and one after, representing a
      trend toward statistical significance. Outpatient encounters increased by 18%,
      missed appointments increased by 34%, psychiatric emergency room visits decreased
      by 47%, and a 69% reduction in inpatient hospital days was observed, all trending
      toward statistical significance. No differences were seen in episodes of violence
      or self-injurious behavior. LIMITATIONS: The study sample was small and there was
      a lack of randomization. CONCLUSION: Results suggest that safety plans can lead
      to improvements in utilization of care and patient engagement. Further research
      is needed to better understand the clinical impact of safety plans on high-risk
      patients.

PMID- 29216754
TI  - Estimating Incidence Rate of Hospital-Treated Self-Harm in Hong Kong Using
      Capture-Recapture Approach.
AB  - BACKGROUND: A surveillance system for self-harm has not been established in Hong
      Kong. The existing data source has an unknown degree of underreporting, and
      therefore a capture-recapture method has been proposed to correct for the
      incompleteness. AIMS: To assess the underestimation of the incidence of self-harm
      cases presenting to hospital in Hong Kong using a capture and recapture method.
      METHOD: Two different yet overlapping hospital administrative datasets of self
      harm were obtained from all public hospitals in Hong Kong. From 2002 to 2011,
      59,473 distinct episodes involving 36,411 patients were identified. A capture
      recapture model considering heterogeneous capture probabilities was applied to
      estimate the number of self-harm episodes. RESULTS: The estimated number of self
      harm incidence was 79,923, equally shared by females and males. Cases of self
      harm by females were more likely to be ascertained than those by males. The
      estimated annual incidence rate of self-harm in Hong Kong from 2002 to 2011
      ranged from 96.4 in 2010 to 132.7 in 2002. LIMITATIONS: The proposed method does
      not include patients who required no medical attention and those where the
      patient consulted private doctors. CONCLUSION: The capture-recapture model is a
      useful method for adjusting the underestimation of self-harm cases from existing
      databases when surveillance system is not available and to reveal some hidden
      patterns.

PMID- 29216755
TI  - Explicit Motives, Antecedents, and Consequences of Direct Self-Injurious
      Behaviors.
AB  - BACKGROUND: Self-injurious behaviors in adolescence are a serious public health
      concern. AIMS: The current study aims to expand our understanding of motives for
      direct self-injurious behaviors (D-SIB). We examined the explicit motives but
      also the actual antecedents and consequences of D-SIB over time. METHOD: As part
      of the Saving and Empowering Young Lives in Europe (SEYLE) study, adolescents
      between the ages of 14 and 18 years from Israel completed self-report
      questionnaires at baseline, 3-month, and 12-month follow-ups. RESULTS: Decreases
      in social support predicted later increases in D-SIB, an effect mediated by
      negative affect. Both peer and parental support also exerted quadratic effects on
      D-SIB. Thus, low as well as high support predicted subsequent D-SIB. In turn, D
      SIB was followed by increased peer and parental support. LIMITATIONS: Our
      methodology relies on self-reports, affected by social desirability and recall
      biases. CONCLUSION: The findings support a causal path for the development of D
      SIB: from interpersonal distress to emotional distress and then to D-SIB. They
      also point to interesting avenues regarding subgroupings of adolescents who self
      injure depending on their motives. Finally, our results reveal that D-SIB,
      although of negative import, might paradoxically be effective in serving certain
      functions such as gaining support from parents and peers.

PMID- 29216756
TI  - The Influence of Perceived Stress and Depression on Suicide-Related Beliefs in
      Caucasian and Indian Adults.
AB  - BACKGROUND AND AIMS: Suicidality research in developing countries, including
      India, faces logistical and cultural challenges. Technology may help address
      these challenges and offer data to providers treating a diverse clientele.
      METHOD: The relationship between perceived stress and suicide-related beliefs was
      examined in two populations: Indians in India (n = 374) and Caucasians in English
      speaking countries (n = 326); the influence of depression on that relationship
      was also explored. The study was conducted via an Internet-based survey. RESULTS:
      Three-way interactions (Ethnicity * Perceived stress * Depression status) were
      observed, predicting strength of the belief that suicide is a solution to
      problems, F(1,679) = 4.18, p < .05, and that suicide is a good option if quality
      of life worsens, F(1,675) = 9.53, p < .01. For both beliefs, Caucasians screening
      positive for depression exhibited the strongest relationship between stress and
      suicide-related beliefs; for Indians, that relationship was not moderated by
      depression status. Caucasians also exhibited a stronger association between
      higher stress and greater belief strength that suicide is a good option assuming
      a steady quality of life than did Indians, F(1,680) = 6.05, p < .05. LIMITATIONS:
      Participants were recruited through a depression screening website; results may
      not generalize to those who are uninterested in depression screening or to those
      who are unwilling or unable to use the internet for that purpose. CONCLUSION: Our
      findings may help to better target interventions to reduce suicidality, for
      example, employ stress reduction techniques for Caucasians who are depressed, and
      monitor suicidality for Indians reporting high stress regardless of depression.

PMID- 29216757
TI  - Assessing Challenges in Low-Income Families to Inform a Life Skills-Based Obesity
      Intervention.
AB  - BACKGROUND: This article describes the formative research undertaken to explore
      challenges of low-income parents of 3-to 5-year-olds to inform a parent-focused
      life skills-based intervention to prevent obesity in preschool-aged children.
      METHOD: A total of 40 parents completed surveys, 30 parents participated in focus
      groups, and 5 community stakeholders participated in individual interviews. In
      each data mode, participants were asked to prioritize a list of challenges
      centered on parenting, family care, and self-care. Survey data were analyzed
      descriptively using SAS, while focus groups and interviews were analyzed for
      emerging themes using ATLAS.ti. RESULTS: Parents reported needing strategies for
      managing children's behavior around picky eating, limits/boundaries, tantrums,
      and routines. Challenges with child behavior management were compounded by
      parents' inability to find affordable fun family activities outside the home and
      difficulties in communicating childrearing expectations to coparents/relatives
      who assisted with child care. Added to these were other competing priorities
      (e.g., financial) that led to the neglect of self, including the inability to
      find "me" time, build relationships, and care for one's health. CONCLUSIONS:
      Interventions that address parenting, family care and self-care challenges of low
      income parents may enhance resilience and support positive changes that can
      promote healthy development in children, including obesity prevention.

PMID- 29216758
TI  - Iron Age Italic population genetics: the Piceni from Novilara (8th-7th century
      BC).
AB  - BACKGROUND: Archaeological data provide evidence that Italy, during the Iron Age,
      witnessed the appearance of the first communities with well defined cultural
      identities. To date, only a few studies report genetic data about these
      populations and, in particular, the Piceni have never been analysed. AIMS: To
      provide new data about mitochondrial DNA (mtDNA) variability of an Iron Age
      Italic population, to understand the contribution of the Piceni in shaping the
      modern Italian gene pool and to ascertain the kinship between some individuals
      buried in the same grave within the Novilara necropolis. SUBJECTS AND METHODS: In
      a first set of 10 individuals from Novilara, we performed deep sequencing of the
      HVS-I region of the mtDNA, combined with the genotyping of 22 SNPs in the coding
      region and the analysis of several autosomal markers. RESULTS: The results show a
      low nucleotide diversity for the inhabitants of Novilara and highlight a genetic
      affinity of this ancient population with the current inhabitants of central
      Italy. No family relationship was observed between the individuals analysed here.
      CONCLUSIONS: This study provides a preliminary characterisation of the mtDNA
      variability of the Piceni of Novilara, as well as a kinship assessment of two
      peculiar burials.

PMID- 29216759
TI  - Pharmaceutical potential of quantum dots.
AB  - Quantum dots (QDs) or fluorescent nanocrystals are designed nanoparticles that
      are promising for several biological and bio-medical applications as well as drug
      delivery and simultaneous cellular imaging. QD's have exhibited promising
      potential primarily in receptor based targeting as a result of their distinctive
      physicochemical properties. Functionalized QDs (f-QDs) have been developed as
      effective, safe, nano-sized smart systems to deliver a wide range of bio-actives.
      Surface modified fluorescent carbon QDs with surface modification have attracted
      attention as targeting ligand to accomplish cellular targeting with enhanced
      specificity. Several surface engineered and conjugated fluorescent carbon QDs are
      presently being explored for the treatment of cancer and the outcome is eagerly
      awaited.

PMID- 29216760
TI  - Intraoperative Mannitol Not Essential During Partial Nephrectomy.
AB  - OBJECTIVE: Intraoperative mannitol is routinely administered for renoprotection
      in partial nephrectomy (PN). However, there is a paucity of evidence supporting
      mannitol's renoprotective effect. We performed a retrospective study of
      mannitol's efficacy in PN. MATERIALS AND METHODS: Using an institutional
      database, patients undergoing PN from 2006 to 2016 were retrospectively
      identified and divided into two groups based on mannitol use. Cases with missing
      serum creatinine measurements were excluded. Mannitol use was dependent on
      surgeon preference. An independent-samples t-test was used to compare 6-month
      postoperative estimated glomerular filtration rate (eGFR) between mannitol groups
      and to compare 6-month eGFR between mannitol dose for patients who received
      mannitol. Multivariate linear regression was used to estimate 6-month eGFR when
      adjusting for multiple covariates that were considered clinically relevant to
      postoperative renal function. RESULTS: Of the patients, 476 patients were
      eligible for analysis and 286 received mannitol. Preoperative eGFR (7.8 +/- 21.4
      mL/minute/1.73 m2 vs 75.3 +/- 23.1 mL/minute/1.73 m2, p = 0.223) and tumor size
      (3.5 +/- 1.7 cm vs 3.4 +/- 1.5 cm, p = 0.532) were matched between the mannitol
      (M+) and no mannitol (M-) groups, whereas warm ischemic time (22.5 +/- 11.2
      minutes vs 15.0 +/- 10.2 minutes, p < 0.001) was longer in the M+ group. There
      was no significant difference in 6-month eGFR between mannitol groups (70.6 +/-
      22.2 mL/minute/1.73 m2 vs 68.0 +/- 23.9 mL/minute/1.73 m2, p = 0.225). No
      significant association between mannitol dose and 6-month eGFR was found.
      Covariates that significantly predicted 6-month eGFR in our multivariate model
      were age (beta = 0.052, p = 0.042) and preoperative eGFR (beta = 0.843, p <
      0.001). In addition, neither the use of renal cooling nor the surgical approach
      (open vs minimally invasive) was significantly associated with 6-month eGFR.
      CONCLUSION: Mannitol did not demonstrate renoprotective effects based on analysis
      of 6-month postoperative eGFR. In addition, neither the surgical approach nor the
      use of renal cooling significantly predicted postoperative renal function.

PMID- 29216761
TI  - Efficient Therapeutic Protein Expression Using Retroviral Replicating Vector with
      2A Peptide in Cancer Models.
AB  - Toca 511, a retroviral replicating vector (RRV), uses an internal ribosomal entry
      site (IRES) to express an optimized yeast cytosine deaminase (yCD2), which
      converts 5-fluorocytosine to 5-fluorouracil. This configuration is genetically
      stable in both preclinical mouse models and human clinical trials. However, the
      use of IRES (~600 bp) restricts choices of therapeutic transgenes due to limits
      in RRV genome size. This study replaced IRES with 2A peptides derived from
      picornaviruses with or without a GSG linker. The data show that GSG-linked 2A
      (g2A) peptide resulted in higher polyprotein separation efficiency than non-GSG
      linked 2A peptide. The study also shows that RRV can tolerate insertion of two
      separate 2A peptides to allow expression of two transgenes without compromising
      the assembly and function of the virus in addition to insertion of a single 2A
      peptide to confirm genetic stability with yCD2, green fluorescent protein, and
      HSV-1 thymidine kinase. In a parallel comparison of the RRV-IRES-yCD2 and RRV-g2A
      yCD2 configurations, the study shows the yCD2 protein expressed from RRV-g2A-yCD2
      has higher activity, resulting in a higher survival benefit in an intracranial
      tumor mouse model. These data enable a wider range of potential product
      candidates that could be developed using the RRV platform.

PMID- 29216762
TI  - Protective effect of astaxanthin on acute cerebral infarction in rats.
AB  - The aim of the study was to investigate the effect of astaxanthin and its
      possible mechanisms on acute cerebral infarction (ACI) in rat model. Male Sprague
      Dawley rats were randomly divided into sham group, model group, and astaxanthin
      treated groups (20, 40, and 80 mg/kg). Neurological examination, the ratio of
      cerebral edema, and histopathology changes were assessed. Moreover, some
      oxidative stress markers were obtained for biochemical analysis, and the
      expression of neurotrophic factors gene was detected by real-time polymerase
      chain reaction (RT-PCR) method. The results showed that treatment with
      astaxanthin notably reduced neurological deficit scores and the ratio of cerebral
      edema compared with the model group. Meanwhile, astaxanthin increased the
      activity of catalase, superoxide dismutase, and glutathioneperoxidase as well as
      decreased the content of malondialdehyde in brain tissue. RT-PCR results showed
      that the expression of brain-derived neurotrophic factor (BDNF) and nerve growth
      factor (NGF) mRNA were increased with astaxanthin treatment. The results
      indicated that astaxanthin could ameliorate ACI followed by suppressing oxidative
      stress and upregulating the expression of BDNF and NGF mRNA.

PMID- 29216763
TI  - Upregulated miR-29c suppresses silica-induced lung fibrosis through the Wnt/beta
      catenin pathway in mice.
AB  - Silicosis is an irreversible lung disease resulting from long-term inhalation of
      occupational dust containing silicon dioxide. However, the pathogenesis of
      silicosis has not been clearly understood yet. Accumulating evidence suggests
      that miR-29 may have a significant anti-fibrotic capacity, meanwhile it may
      relate to Wnt/beta-catenin pathway. The purpose of this study was to discuss the
      role of miR-29 in the progression of silicosis. A lentiviral vector was
      constructed, named Lv-miR-29c, which was overexpressing miR-29c. In vivo,
      intratracheal treatment with Lv-miR-29c significantly increased expression of miR
      29c, and reduced expression of beta-catenin, matrix metalloproteinase (MMP)-2,
      and MMP-9 in the lung and levels of transforming growth factor-beta 1 (TGF-beta1)
      and interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and notably attenuated
      pulmonary fibrosis as evidenced by hydroxyproline content in silica-administered
      mice. These results indicated that miR-29c inhibited the development of silica
      induced lung fibrosis. Thus, miR-29c may be a candidate target for silicosis
      treatment via its regulation of the Wnt/beta-catenin pathway.

PMID- 29216764
TI  - Quantifying the Center of Elbow Rotation: Implications for Medial Collateral
      Ligament Reconstruction.
AB  - BACKGROUND: Medial collateral ligament (MCL) reconstruction of the elbow mandates
      precise characterization of where the centerline of elbow rotation projects onto
      the medial epicondyle (ME). A muscle-splitting approach allows the flexor
      pronator muscles to remain attached to the ME and facilitates visualization of
      the MCL remnant, the sublime tubercle, and the ulnohumeral joint line. Knowledge
      of where the centerline of rotation intersects the ME relative to the ulnohumeral
      joint line may assist the surgeon during placement of the proximal drill hole.
      METHODS: Models were created from the computed tomography scans of 29 normal
      elbows. The centerline of rotation, center of the trochlea, sublime tubercle, and
      ulnohumeral joint line were identified. Measurements were taken from the
      ulnohumeral joint line to the center of the trochlea and to the centerline of
      rotation in the sagittal view and along the course of the MCL. RESULTS: The
      centerline of rotation intersected the ME in a consistent location. With the
      elbow flexed 90 degrees , the trochlea center and the centerline of rotation are
      essentially in line with each other. There are significant differences between
      the distances from the ulnohumeral joint line to the center of the trochlea and
      to the centerline of rotation in both the sagittal view and along the course of
      the MCL. CONCLUSIONS: The centerline of rotation is located 14.31 mm (1.70) from
      the ulnohumeral joint line in the sagittal view and 16.54 mm (2.09) from the
      ulnohumeral joint line along the course of the MCL.

PMID- 29216765
TI  - Using the Intervention Mapping and Behavioral Intervention Technology Frameworks:
      Development of an mHealth Intervention for Physical Activity and Sedentary
      Behavior Change.
AB  - Few interventions to promote physical activity (PA) adapt dynamically to changes
      in individuals' behavior. Interventions targeting determinants of behavior are
      linked with increased effectiveness and should reflect changes in behavior over
      time. This article describes the application of two frameworks to assist the
      development of an adaptive evidence-based smartphone-delivered intervention aimed
      at influencing PA and sedentary behaviors (SB). Intervention mapping was used to
      identify the determinants influencing uptake of PA and optimal behavior change
      techniques (BCTs). Behavioral intervention technology was used to translate and
      operationalize the BCTs and its modes of delivery. The intervention was based on
      the integrated behavior change model, focused on nine determinants, consisted of
      33 BCTs, and included three main components: (1) automated capture of daily PA
      and SB via an existing smartphone application, (2) classification of the
      individual into an activity profile according to their PA and SB, and (3)
      behavior change content delivery in a dynamic fashion via a proof-of-concept
      application. This article illustrates how two complementary frameworks can be
      used to guide the development of a mobile health behavior change program. This
      approach can guide the development of future mHealth programs.

PMID- 29216766
TI  - Vanillin mitigates the adverse impact of cisplatin and methotrexate on rat
      kidneys.
AB  - The present study investigated the probable protective effect of vanillin (VLN)
      against kidney injury induced by cisplatin (CSN) and methotrexate (MTX) in rats.
      The rats received a single injection of either CSN (7.5 mg/kg, i.p.) or MTX (20
      mg/kg, i.p.). VLN treatment (150 mg/kg/day, i.p.) was started 1 day before
      administration of the nephrotoxic agents and continued for 7 days. Both CSN and
      MTX significantly increased serum creatinine, cystatin C, and neutrophil
      gelatinase-associated lipocalin and kidney tissue renal malondialdehyde,
      inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-18,
      nuclear factor-kappaB p65, cytosolic cytochrome C, and caspase-3 and
      significantly decreased renal total antioxidant capacity and Bcl-2/Bax ratio in
      rats. VLN significantly ameliorated the changes of biochemical parameters induced
      by CSN and MTX. VLN also significantly reduced CSN- and MTX-induced
      histopathological injury and the expression of Fas ligand in rat kidneys. In
      conclusion, VLN significantly protected against CSN- and MTX-induced kidney
      injury in rats by inhibiting oxidative/nitrosative stress, inflammation, and
      apoptosis.

PMID- 29216768
TI  - A mysterious case of complex regional pain syndrome in a 9-year-old girl.
AB  - PURPOSE: To describe the clinical manifestation and the treatment of complex
      regional pain syndrome type II in childhood. METHODS: Using information on the
      symptoms, diagnosis, rehabilitation and outcome of a young patient with complex
      regional pain syndrome type II. RESULTS: A 9-year -old girl had severe pain in
      the region of the left foot, signs of a common fibular nerve entrapment,
      hyperalgesia not limited to the distribution of the injured nerve, weakness and
      temperature asymmetry unknown origin. She consulted few doctor's before she was
      given the right diagnosis of complex regional pain syndrome type II. Following
      the diagnosis the treatment started, it included intensive physiotherapy,
      electrical therapy and also supportive psychological therapy. Half a year later,
      the patient was free of the daily pain and returned to all physical activity
      without any restrictions. CONCLUSIONS: The case report illustrates that
      peripheral nerve compression or injuries specifically, complex regional pain
      syndrome type II, should be taken into consideration when evaluating children
      with weakness and pain of the lower or upper limb. Implication of rehabilitation
      Raising the awareness of complex regional pain syndrome in the childhood is
      essential for an early diagnosis and appropriate treatment. The treatment options
      include early and adequate pain management inclusive electrical therapy and
      physiotherapy. Psychological therapy helps to avoid psychological stress reaction
      and the disease negative impact on the child's education and sports and the
      family social life.

PMID- 29216767
TI  - Prevalence and factors associated with gluten sensitivity in inflammatory bowel
      disease.
AB  - OBJECTIVES: Gluten sensitivity (GS) arises with celiac disease and has also been
      found in non-celiac disorders, although its characteristics in inflammatory bowel
      disease (IBD) are unclear. This study evaluated the prevalence of GS and factors
      associated with GS in IBD. METHODS: Adult IBD patients at a tertiary-care medical
      center completed a survey of their demographics, medical history, family history,
      social history and symptoms. Data on IBD characteristics were abstracted from the
      medical records. Descriptive analyses estimated the prevalence of GS.
      Multivariable logistic regression assessed the association between GS and patient
      or disease factors. RESULTS: Of 102 IBD patients (55 Crohn's disease [CD], 46
      ulcerative colitis [UC] and 3 IBD-unclassified), GS was reported in 23.6 and
      27.3% of CD and UC patients, respectively. Common symptoms included fatigue,
      abdominal pain, diarrhea, bloating and hematochezia. There was no difference in
      these symptoms when comparing patients with and without GS. When evaluating IBD
      related factors, GS was associated with having had a recent flare (adjusted odds
      ratio [aOR] 7.4; 95% confidence interval [CI] 1.6-34.1), stenotic disease in CD
      (aOR 4.7; 95% CI 1.1-20.2) and dermatologic manifestations (aOR 5.5; 95% CI 1.2
      24.1). CONCLUSION: GS was common in IBD and associated with having had a recent
      flare. GS may be transient for some patients, whereby dietary recommendations
      during and after a flare could focus on the avoidance of specific food triggers
      with possible reintroduction of these foods over time. This study prompts further
      prospective investigation into the temporal evolution of GS in IBD.

PMID- 29216769
TI  - Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the
      setting of hypoxia/reoxygenation in cardiac cells.
AB  - Zinc plays a role in autophagy and protects cardiac cells from
      ischemia/reperfusion injury. This study aimed to test if zinc can induce
      mitophagy leading to attenuation of mitochondrial superoxide generation in the
      setting of hypoxia/reoxygenation (H/R) in cardiac cells. H9c2 cells were
      subjected to 4 h hypoxia followed by 2 h reoxygenation. Under normoxic
      conditions, treatments of cells with ZnCl2 increased both the LC3-II/LC3-I ratio
      and GFP-LC3 puncta, implying that zinc induces autophagy. Further experiments
      showed that endogenous zinc is required for the autophagy induced by starvation
      and rapamycin. Zinc down-regulated TOM20, TIM23, and COX4 both in normoxic cells
      and the cells subjected to H/R, indicating that zinc can trigger mitophagy. Zinc
      increased ERK activity and Beclin1 expression, and zinc-induced mitophagy was
      inhibited by PD98059 and Beclin1 siRNA during reoxygenation. Zinc-induced Beclin1
      expression was reversed by PD98059, implying that zinc promotes Beclin1
      expression via ERK. In addition, zinc failed to induce mitophagy in cells
      transfected with PINK1 siRNA and stabilized PINK1 in mitochondria. Moreover, zinc
      induced PINK1 stabilization was inhibited by PD98059. Finally, zinc prevented
      mitochondrial superoxide generation and dissipation of mitochondrial membrane
      potential (DeltaPsim) at reoxygenation, which was blocked by both the Beclin1 and
      PINK1 siRNAs, suggesting that zinc prevents mitochondrial oxidative stress
      through mitophagy. In summary, zinc induces mitophagy through PINK1 and Beclin1
      via ERK leading to the prevention of mitochondrial superoxide generation in the
      setting of H/R. Clearance of damaged mitochondria may account for the
      cardioprotective effect of zinc on H/R injury.

PMID- 29216770
TI  - Maternal age over 40 years and pregnancy outcome: a hospital-based survey.
AB  - OBJECTIVE: Increased risk for adverse pregnancy outcomes with advancing maternal
      age has been described but the strength of association remains debated,
      particularly in presence of confounding factors such as parity, twin pregnancy
      and pregnancy from assisted reproductive technologies. The aim of this study was
      to evaluate pregnancy outcomes in a large cohort of women aged over 40 years. The
      hypothesis was that advanced maternal age may be an independent risk factor for
      adverse pregnancy outcome. STUDY DESIGN: We reviewed the clinical records of
      56,211 women who delivered at Sant'Anna University Hospital, Turin, Italy, in the
      period between 2009 and 2015. Of these, 3798 women aged over 40 years were
      divided into two age groups (40 - 44 years and >=45 years). Women of any parity,
      with singleton or twin pregnancies, or with assisted reproductive technology
      pregnancies were included. Women aged less than 40 years were considered as
      controls. Primary outcome measures were maternal and perinatal complications.
      Comparisons were performed using Chi-square test and Fisher's exact test.
      Univariate analysis and logistic regression analysis were performed to test the
      possible independent role of maternal age as a risk factor for adverse pregnancy
      outcome. RESULTS: Maternal age was an independent risk factor for gestational
      diabetes (age 40-44 years: odds ratios (OR) 2.10, 95% CI 1.80-2.45; age >=45
      years: OR 2.83, 95% CI 1.79-4.46) and early-onset preeclampsia (age 40-44 years:
      OR 2.10, 95% CI 1.63-2.70; age >=45 years: OR 3.16, 95% CI 1.68-5.94). The risk
      for placenta praevia was higher in the women aged 40-44 years (OR 1.87, 95% CI
      1.36-2.57). Neonatal outcomes were similar among groups, except for the rate of
      birth weight less than 2500 g, which was higher in women aged 40-44 years (OR
      1.27, 95% CI 1.12-1.42). However, older women showed an overall higher incidence
      of preterm birth. CONCLUSIONS: Maternal age over 40 years is an independent risk
      factor for adverse pregnancy outcomes, particularly for the mother. Pregnancies
      in women over 40 years should be considered at risk and carefully monitored with
      individualized care protocols.

PMID- 29216771
TI  - Survey of the functional priorities in patients with disability due to
      neuromuscular disorders.
AB  - TITLE: Survey of the functional priorities in patients with disability due to
      neuromuscular disorders. OBJECTIVE: This study attempts to determine the
      functional priorities for patients with neuromuscular disorders. METHODS: A
      survey asking about functional priorities with respect to activities of daily
      living, ankle foot orthotic design, and assistive device design, was distributed
      to patients with neuromuscular disorders to assess the needs of patients from
      their perspectives. Descriptive statistics were used to analyse answers. RESULTS:
      A total of 171 subjects with neuromuscular disorders responded to the
      questionnaire. Of the respondents with weakness in both the upper and lower
      extremities, 45% stated that if they had to choose between correction of one or
      the other, they would prefer that of their lower extremities. Activities that
      patients most frequently wanted to gain independence with were mobility and
      transfers (46%), followed by toilet use and hygiene (32%). The most popular
      control mechanism of an assistive device was voice activation (35%). CONCLUSION:
      This study assessed the functional priorities of those with neuromuscular
      disorders. Although such individuals can experience a range of weakness in the
      upper and/or lower extremities, common functional priorities were reported:
      independence with mobility, transfers, toilet use and hygiene. Knowledge of these
      priorities will help guide development of assistive devices that will restore
      function in the future. Implications for Rehabilitation     Neuromuscular
      Disorders  * Neuromuscular disorders result in disabling weakness; there are few
      cures and many are unable to carry out activities of daily living.  * Information
      that would be helpful in determining functional priorities is limited.  * In a
      survey of 171 patients with neuromuscular disorders, functional priorities
      included mobility and transfers (46%), followed by toilet use and hygiene (32%). 
      * Of the respondents with weakness in both the upper and lower extremities, 45%
      stated that if they had to choose between correction of one or the other, they
      would prefer that of their lower extremities.  * If an assistive device were to
      be created to help those with neuromuscular disorders, the most popular control
      mechanism would be voice activation (35%).

PMID- 29216772
TI  - Proteomic Cinderella: Customized analysis of bulky MS/MS data in one night.
AB  - Proteomic challenges, stirred up by the advent of high-throughput technologies,
      produce large amount of MS data. Nowadays, the routine manual search does not
      satisfy the "speed" of modern science any longer. In our work, the necessity of
      single-thread analysis of bulky data emerged during interpretation of HepG2
      proteome profiling results for proteoforms searching. We compared the
      contribution of each of the eight search engines (X!Tandem, MS-GF[Formula: see
      text], MS Amanda, MyriMatch, Comet, Tide, Andromeda, and OMSSA) integrated in an
      open-source graphical user interface SearchGUI ( http://searchgui.googlecode.com
      ) into total result of proteoforms identification and optimized set of engines
      working simultaneously. We also compared the results of our search combination
      with Mascot results using protein kit UPS2, containing 48 human proteins. We
      selected combination of X!Tandem, MS-GF[Formula: see text] and OMMSA as the most
      time-efficient and productive combination of search. We added homemade java
      script to automatize pipeline from file picking to report generation. These
      settings resulted in rise of the efficiency of our customized pipeline
      unobtainable by manual scouting: the analysis of 192 files searched against human
      proteome (42153 entries) downloaded from UniProt took 11[Formula: see text]h.

PMID- 29216773
TI  - Foreword.

PMID- 29216774
TI  - Chinese fetal biometry: reference equations and comparison with charts from other
      populations.
AB  - OBJECTIVE: This study aimed to construct new reference charts and equations for
      fetal biometry from Chinese fetuses at 15-40 weeks and to compare them with
      previous references. METHOD: This was a prospective, cross-sectional study of
      singleton pregnancies in patients with a confirmed gestational age who underwent
      ultrasound examinations between the 15th and 40th weeks of gestation. Each woman
      was selected only once for this study. Biparietal diameter (BPD), head
      circumference (HC), abdominal circumference (AC), and femur length (FL) were
      recorded. For each measurement, separate regression models were fitted to
      estimate the mean and standard deviation at each menstrual age. Z-scores were
      calculated with our reference equations for comparison with other references.
      RESULTS: New charts and reference equations involving 7553 Chinese women were
      created for BPD, HC, AC, and FL. Reference equations were cubic models.
      Prediction intervals for the new reference charts were similar to those of
      previous references, but with some slight differences. The main difference in our
      fetal biometric measurements compared with those of Korea and Hong Kong was the
      FL. CONCLUSIONS: We report new Chinese reference charts and equations for fetal
      biometry. These reference charts and equations are available for clinical use in
      obstetric ultrasound studies for the Chinese population.

PMID- 29216775
TI  - Value of ultrasound in diagnosis of radial nerve palsy with hourglass-like
      constrictions without extrinsic compression: a case report.

PMID- 29216776
TI  - The hand injury caused by cutting avocado in 18 patients.

PMID- 29216777
TI  - The long and winding road: stem cells for cystic fibrosis.
AB  - INTRODUCTION: Cystic fibrosis (CF) is a genetic syndrome with a high mortality
      rate due to severe lung disease. Despite having several drugs targeting specific
      mutated CFTR proteins already in clinical trials, new therapies, based on stem
      cells, are also emerging to treat those patients. Areas covered: The authors
      review the main sources of stem cells, including embryonic stem cells (ESCs),
      induced-pluripotent stem cells (iPSCs), gestational stem cells, and adult stem
      cells, such as mesenchymal stem cells (MSCs) in the context of CF. Furthermore,
      they describe the main animal and human models of lung physiology and pathology,
      involved in the optimization of these stem cell-applied therapies in CF. Expert
      opinion: ESCs and iPSCs are emerging sources for disease modeling and drug
      discovery purposes. The allogeneic transplant of healthy MSCs, that acts
      independently to specific mutations, is under intense scrutiny due to their
      secretory, immunomodulatory, anti-inflammatory and anti-bacterial properties. The
      main challenge for future developments will be to get exogenous stem cells into
      the appropriate lung location, where they can regenerate endogenous stem cells
      and act as inflammatory modulators. The clinical application of stem cells for
      the treatment of CF certainly warrants further insight into pre-clinical models,
      including large animals, organoids, decellularized organs and lung
      bioengineering.

PMID- 29216778
TI  - Costs and effectiveness of hearing conservation programs at 14 US metal
      manufacturing facilities.
AB  - OBJECTIVE: This study characterised overall and specific costs associated with
      hearing conservation programmes (HCPs) at US metal manufacturing sites, and
      examined the association between these costs and several noise-induced hearing
      loss (NIHL) outcomes. DESIGN: We interviewed personnel and reviewed records at
      participating facilities. We also measured noise for comparison to the ten-year
      average of measurements made by each facility. NIHL outcomes assessed included
      rates of standard threshold shifts (STS) and high-frequency hearing loss, as well
      as prevalence of hearing impairment, for each participating facility. We used
      linear regression to identify per-person HCP costs that best predicted the NIHL
      outcomes. STUDY SAMPLE: We evaluated 14 US metal manufacturing facilities
      operated by a single company. RESULTS: Annual HCP costs ranged from roughly
      $67,000 to $397,000 (average $308 +/- 80 per worker). Our full-shift noise
      measurements (mean 83.1 dBA) showed good agreement with the facilities'
      measurements (mean 82.6 dBA). Hearing impairment prevalence was about 15%
      overall. Higher expenditures for training and hearing protector fit-testing were
      significantly associated with reduced STS prevalence. Higher training
      expenditures were also related to lower hearing impairment prevalence and high
      frequency hearing loss rates. CONCLUSIONS: HCP costs were substantial and
      variable. Increased workplace spending on training and fit-testing may help
      minimise NIHL.

PMID- 29216779
TI  - The plaque and gingivitis inhibiting capacity of a commercially available
      mouthwash containing essential oils and ethyl lauroyl arginate. A randomized
      clinical trial.
AB  - OBJECTIVE: A commercially available mouth rinse with ethyl lauroyl arginate and
      essential oils claims to have better antimicrobial properties than the
      traditional essential oil products. The aim of this study was to compare the
      plaque and gingivitis inhibiting effect of the commercial product containing
      essential oils with ethyl lauroyl arginate with one placebo and one negative
      control in a modified experimental gingivitis model. MATERIALS AND METHODS: In
      three groups of healthy volunteers, experimental gingivitis was induced and
      monitored over 21 d, simultaneously treated with the commercial test solution,
      21.6% hydro-alcohol solution and sterile water, respectively. The maxillary right
      quadrant of each individual received mouthwash only, whereas the maxillary left
      quadrant was subject to both rinsing and mechanical oral hygiene. Compliance and
      side effects were monitored at d 7, 14, and 21. Plaque and gingivitis scores were
      obtained at baseline and d 21. RESULTS AND CONCLUSION: Although the commercial
      product containing essential oils with ethyl lauroyl arginate performed
      statistically significantly better regarding average plaque scores on all
      surfaces combined than the placebo (p = .018) and negative control (p = .003)
      when no mechanical tooth cleaning was performed, the product still left the
      patient with enough plaque to cause gingivitis and thus seemed of questionable
      clinical benefit to the patient. ClinicalTrials.gov Identifier is NCT02884817.

PMID- 29216780
TI  - Using cost-analyses to inform health professions education - The economic cost of
      pre-clinical failure.
AB  - BACKGROUND: Student failure creates additional economic costs. Knowing the cost
      of failure helps to frame its economic burden relative to other educational
      issues, providing an evidence-base to guide priority setting and allocation of
      resources. The Ingredients Method is a cost-analysis approach which has been
      previously applied to health professions education research. In this study, the
      Ingredients Method is introduced, and applied to a case study, investigating the
      cost of pre-clinical student failure. METHODS: The four step Ingredients Method
      was introduced and applied: (1) identify and specify resource items, (2) measure
      volume of resources in natural units, (3) assign monetary prices to resource
      items, and (4) analyze and report costs. Calculations were based on a
      physiotherapy program at an Australian university. RESULTS: The cost of failure
      was L5991 per failing student, distributed across students (70%), the government
      (21%), and the university (8%). If the cost of failure and attrition is
      distributed among the remaining continuing cohort, the cost per continuing
      student educated increases from L9923 to L11,391 per semester. CONCLUSIONS: The
      economics of health professions education is complex. Researchers should consider
      both accuracy and feasibility in their costing approach, toward the goal of
      better informing cost-conscious decision-making.

PMID- 29216781
TI  - Comparative analyses of species delimitation methods with molecular data in
      snappers (Perciformes: Lutjaninae).
AB  - The integration of approaches that allow the incorporation of stochasticity of
      gene histories with phylogenetic methods resulted in new approaches for the old
      issue of species delimitation. Nevertheless, coalescent methods seem problematic
      for taxa with large effective population size and shallow temporal
      diversification (like marine fishes). Here, we investigate the performance of
      single-locus (cytochrome oxidase 1, commonly used in DNA barcoding initiatives)
      methods for molecular species delimitation in snappers of Lutjaninae from the
      Western Atlantic and Pacific Eastern. Our results show incongruences among
      methods. ABGD, PTP and mPTP trend towards a lower number of estimated species.
      Phylogenetic-coalescent methods with single threshold were majority congruent for
      a same number of lineages. On the other hand, algorithms with multiple thresholds
      tend to estimate a higher number of potential species. We do not endorse the use
      of single-locus for species delimitation, but we do reinforce that single-locus
      data is sufficient to flag many problems.

PMID- 29216782
TI  - Reduction in Central Line-Associated Bloodstream Infections Correlated With the
      Introduction of a Novel Silver-Plated Dressing for Central Venous Catheters and
      Maintained for 6 Years.
AB  - OBJECTIVE: To assess a novel silver-plated dressing (SD) for central venous
      catheters in comparison to chlorhexidine gluconate-impregnated sponge (CHGIS)
      dressings in preventing central line-associated bloodstream infections (CLABSIs)
      in adult intensive care unit (ICU) patients. DESIGN: Retrospective cohort study.
      SETTING: Tampa General Hospital, an academic medical tertiary care center.
      PATIENTS: All adult ICU patients of an academic medical tertiary care center from
      January 2009 to December 2010. MEASUREMENTS AND MAIN RESULTS: A total of 3189
      patient records were studied from 7 different ICUs during the 2-year period.
      Patients received either CHGIS dressings (January 2009-December 2009) or SDs
      (January 2010-December 2010). Primary outcomes measured were CLABSI rates per
      1000 catheter days and ICU length of stay. There were 30 696 catheter days with
      CHGIS dressings and 31 319 catheter days with SDs. There was a statistically
      significant decrease in the rate of CLABSI per 1000 catheter days in the SD
      group, from 2.38 to 1.28 ( P = .001), with an absolute risk reduction of 1.1.
      There was a significantly lower incidence in the rate of CLABSI per 1000 catheter
      days in the SD group (incidence rate ratio [IRR] = 0.54, 95% confidence interval
      [CI]: 0.36-0.80). The relative risk of CLABSI in the SD group was 0.502 (95% CI:
      0.340-0.730; P < .001). If SDs are used on all catheters, the decreased rate of
      CLABSIs observed would calculate to a cost savings of US$4070 to US$39 600 per
      1000 catheter days. After successful implementation of the SD, we observed
      significant reductions in CLABSI rates and a sustained reduction in the
      subsequent 6 years. CONCLUSION: Use of SDs is associated with a significant
      decrease in CLABSI rates in adult ICU patients compared to CHGIS dressings, with
      an estimated cost savings of US$4070 to US$39 600 per 1000 catheter days.

PMID- 29216783
TI  - Moving towards improved vaccines for Toxoplasma gondii.
AB  - INTRODUCTION: Toxoplasma gondii is an intracellular parasitic protozoan that
      infects almost all warm-blooded animals and humans, resulting in threats to
      public health and economic losses. Despite continuous research efforts, there are
      still very few effective strategies against toxoplasmosis. In the past few years,
      numerous vaccination experiments have been performed to control T. gondii
      infection. Areas covered: In this review, the authors summarize the development
      of T. gondii vaccines with proper adjuvants, ranging from live or live-attenuated
      vaccines to protein vaccines, DNA vaccines, epitope vaccines and novel vaccines.
      They also highlight the challenges involved in the development of T. gondii
      vaccines, including specific impediments and shortcomings. Expert opinion: Moving
      towards the development of effective vaccines against T. gondii is not only a
      tedious mission but also a difficult challenge. Future studies should consider
      new approaches and strategies for vaccine development, particularly novel
      vaccines and genetic adjuvants, as well as optimizing immunization protocols and
      evaluation criteria.

PMID- 29216784
TI  - Evaluation of peripheral serotonin content and alpha2-adrenergic receptor
      function as potential markers for life-long recurrent depressive disorder by
      using methodological improvements.
AB  - OBJECTIVE: We aimed to evaluate the role and the relations between peripheral
      platelet serotonin content, blood plasma serotonin concentration and the function
      of platelet alpha2-adrenergic receptors (alpha2-AR) as potential state or trait
      biomarkers for recurrent depressive disorder (RDD). METHODS: 26 drug-free
      patients with life-long RDD and 31 healthy controls were included in the study.
      Several methodological improvements in blood collection and platelet isolation
      were implemented following the present standards in Haematology and Light
      transmission aggregometry. RESULTS: Our results have shown lower platelet
      serotonin content, higher plasma serotonin concentration and desensitization of
      platelet alpha2-AR in patients with RDD. The variables were found heterogeneous
      and mainly influenced by the clinical characteristics of the current episode.
      High amplitude of the alpha2-AR correlated with severe anxious symptoms and high
      platelet serotonin content (as well as low plasma serotonin levels) were
      associated with psychotic symptoms. CONCLUSIONS: The evaluated peripheral markers
      reflect only state (but not trait) abnormalities in patients with current severe
      episode of RDD. The observed peripheral alpha2-AR and serotonin abnormalities are
      mutually not related and they are probably triggered by different mechanisms.

PMID- 29216785
TI  - ORBIT score: an useful predictor of small bowel rebleeding in patients under
      chronic anticoagulation.
AB  - BACKGROUND AND STUDY AIMS: Available scoring systems to assess the risk for major
      bleeding in patients on chronic anticoagulation seem inadequate in predicting
      higher diagnostic yields of small bowel capsule endoscopy (SBCE) or higher
      rebleeding rates in patients with suspected small bowel bleeding. The aim of this
      study was to evaluate the ability of the new ORBIT score in predicting positive
      findings of SBCE or higher rebleeding rates in chronically anticoagulated
      patients with suspected small bowel bleeding. PATIENTS AND METHODS: Retrospective
      analysis of 570 patients who consecutively underwent SBCE for the study of
      suspected small bowel bleeding. For each of the 67 patients who were on chronic
      anticoagulation, ORBIT score (Older age, Reduced hemoglobin/hematocrit, Bleeding
      history, Insufficient kidney function and Treatment with antiplatelets) was
      calculated. Patients were classified as high-risk (ORBIT score >=4) or
      low/intermediate-risk (ORBIT score <4). Data on SBCE findings, diagnostic yield
      and rebleeding were compared between groups. RESULTS: When ORBIT score was
      calculated, 41 and 26 patients were classified as low/intermediate-risk and high
      risk, respectively. When low/intermediate-risk and high-risk groups were
      compared, no differences were found in the diagnostic yield of SBCE (39.0% vs.
      23.1%; p = .176). However, in high-risk patients, rebleeding was significantly
      more common than in low/intermediate-risk patients (80.0% vs. 36.6%; p = .003).
      CONCLUSIONS: In patients presenting with suspected small bowel bleeding and on
      chronic anticoagulation, the new ORBIT score seems promising in identifying those
      with a higher risk of rebleeding, in whom a closer follow-up and a more
      aggressive diagnostic and therapeutic strategy is advisable.

PMID- 29216786
TI  - A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han
      Chinese children with autism spectrum disorder.
AB  - PURPOSE: Autism spectrum disorder (ASD) is a group of developmental brain
      disorders caused by genetic and environmental factors. The objective of this
      study was to investigate whether single nucleotide polymorphisms (SNPs) in genes
      related to immune function were associated with ASD in Chinese Han children.
      MATERIALS AND METHODS: A total of 201 children with ASD and 200 age- and gender
      matched healthy controls were recruited from September 2012 to June 2106. A
      TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698
      and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2. Case-control
      and case-only studies were performed to determine the contribution of SNPs to the
      predisposition of disease and its severity, respectively. RESULTS: Our results
      revealed that the genotypes and allele frequencies of these SNPs were not
      significantly associated with childhood ASD and its severity in this population.
      CONCLUSIONS: Results of our study suggest that these SNPs are not predictors of
      childhood ASD in the Chinese Han population. The discrepant results suggest the
      predictor roles of SNPs have to be determined in different ethnic populations due
      to genetic heterogeneity of ASD.

PMID- 29216787
TI  - MEK inhibitors under development for treatment of non-small-cell lung cancer.
AB  - INTRODUCTION: The mitogen-activated protein kinase (MAPK) pathway is intimately
      implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC).
      Aberrant MAPK signaling resulting from the upstream activating mutations
      converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK
      inhibition an attractive strategy for the treatment of NSCLC. Several MEK
      inhibitors have demonstrated anticancer activity in patients with NSCLC. Areas
      covered: In this article, we discuss the biological rationale for the use of MEK
      inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the
      treatment of NSCLC, from initial phase I studies to phase II/III studies, both as
      monotherapy or in combination with other anticancer agents. Expert opinion:
      Trametinib in combination with the BRAF inhibitor dabrafenib represents the first
      MEK1/2 inhibitor containing regimen that is approved for advanced BRAFV600E
      mutant NSCLC. Other MEK1/2 inhibitors that are also in advanced stages of
      clinical development include selumetinib, cobimetinib, and binimetinib. Several
      studies of MEK inhibitor combination therapies are underway, including trials
      using combined MEK inhibition and immune checkpoint blockade. Further research
      aimed at discovering biomarkers of response and resistance to MEK1/2 inhibitors
      will be needed to develop rational combination strategies for the treatment of
      NSCLC driven by aberrant MAPK signaling.

PMID- 29216788
TI  - Insights into teaching a complex skill: Threshold concepts and troublesome
      knowledge in electroencephalography (EEG).
AB  - BACKGROUND: Threshold concepts (TCs) are defined as ideas within a discipline
      that are often conceptually difficult ("troublesome"), but when learned,
      transform a learner's understanding. Electroencephalography (EEG) has been
      recognized as a conceptually difficult field in neurology, and a study of
      threshold concepts in EEG may provide insights into how it is taught and learned.
      METHODS: Semi-structured interviews were performed with 12 EEG experts in the US
      and Canada. Experts identified potential TCs and troublesome knowledge, and
      explored how these concepts were taught and learned. Interview transcripts were
      coded and analyzed using a general thematic analysis approach, based on the core
      elements of the threshold concepts framework. RESULTS: One concept (polarity)
      emerged most clearly as a threshold concept. Other troublesome areas included
      pattern interpretation and clinical significance, but these lacked some of the
      characteristics of TCs. Several themes emerged, including the role of TCs and
      troublesome knowledge in determining expertise and the role of prior experience.
      CONCLUSIONS: We have used the threshold concepts framework to explore potential
      barriers to learning, suggest ways to support learners, and identify potential
      points of emphasis for teaching and learning EEG. A similar approach could be
      applied to the study of teaching and learning in other conceptually difficult
      areas of medical education.

PMID- 29216789
TI  - Open book exams: A potential solution to the "full curriculum"?
AB  - In this Personal View article, as curriculum designers, we consider whether there
      is a place for open book exams in Medical School curricula. Specifically, at a
      time when medical teachers complain about the difficulties of delivering a full
      curriculum, we propose that open book assessment approaches may help to free up
      the curriculum as learners become less reliant on memorizing facts. Moreover
      deeper learning of higher level outcomes can be achieved and more authentic
      assessment approaches undertaken. We also look at the recent literature and
      consider reasons, both for and against open book exams, at theoretical and
      practical levels. Though there are potential challenges with delivering an open
      book exam, we conclude that the benefits appear to outweigh these difficulties.
      As part of a balanced assessment strategy it may be necessary and timely to adopt
      open book exams.

PMID- 29216790
TI  - Dual Therapy Appears Superior to Monotherapy for Low-Income Individuals With
      Newly Diagnosed Type 2 Diabetes.
AB  - BACKGROUND: There are variable recommendations regarding initiating monotherapy
      or dual therapy in patients with newly diagnosed type 2 diabetes (T2D). Clear
      initial strategies are of particular importance in underserved settings where
      access to care and financial burdens are significant barriers. OBJECTIVES: To
      provide descriptive data of metabolic outcomes to therapy regimens for low-income
      individuals with newly diagnosed T2D placed on oral hypoglycemic agents (OAs).
      METHODS: We conducted a retrospective chart review of low-income individuals with
      newly diagnosed T2D initiated on OAs. We provided descriptive data and then
      evaluated the effects of OA regimens (ie, mono-, dual-, transition [from mono to
      dual or vice versa] therapy) on hemoglobin A1c (A1c) (baseline to 12 months).
      RESULTS: A total of 309 patients were included in the study. At 12 months, the
      mean decrease in A1c for the entire sample was -2.36% (9.37% to 7.01%). Patients
      prescribed dual therapy had a greater change of A1c compared to those taking
      monotherapy with metformin (-1.11%, P < .01). Patients who transitioned therapies
      did not differ in change of A1c compared to monotherapy. CONCLUSION: Initiation
      of dual therapy was superior to metformin monotherapy or transitioning therapies
      and may be preferred for low-income individuals with newly diagnosed T2D.

PMID- 29216791
TI  - The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the
      disease susceptibility and the clinical features of the Chinese patients of sCJD
      and FFI.
AB  - Prion diseases are a group of fatal neurodegenerative disorders that affect
      humans and animals. Besides of the pathological agent, prion, there are some
      elements that can influence or determine susceptibility to prion infection and
      the clinical phenotype of the diseases, e.g., the polymorphism in PRNP gene.
      Another polymorphism in ZBTB38-RASA2 has been observed to be associated with the
      susceptibility of sporadic Creutzfeldt-Jacob disease (sCJD) in UK. MicroRNAs are
      endogenous small noncoding RNAs that control gene expression by targeting mRNAs
      and triggering either translation repression or RNA degradation. In this study,
      two polymorphic loci in miR-146a (rs2910164 and rs57095329) and one locus in
      ZBTB38-RASA2 (rs295301) of 561 Chinese patients of sCJD and 31 cases of fatal
      familial insomnia (FFI) were screened by PCR and sequencing. Our data did not
      figure out any association of those three SNPs with the susceptibility of sCJD.
      However, a significant association of the SNP of rs57095329 in miR-146a showed
      the association with the susceptibility of FFI. Additionally, the SNP of
      rs57095329 showed statistical significances with the appearances of mutism and
      the positive of cerebrospinal fluid (CSF) protein 14-3-3 in sCJD patients, while
      the SNP of ZBTB38-RASA2 was significantly related with the appearance of
      myoclonus in sCJD patients. It indicates that the SNPs of ZBTB38-RASA2 and miR
      146a are not associated with the susceptibility of the Chinese sCJD patients, but
      may influence the appearances of clinical manifestations somehow.

PMID- 29216792
TI  - Quadriceps muscle thickness changes in patients with aneurysmal subarachnoid
      hemorrhage during the acute phase.
AB  - Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening
      condition that often leads to severe disability in relatively young and healthy
      people. This disability is physical in many aSAH survivors, so muscle dysfunction
      may be an important factor in the functional level of these patients. Thus,
      measuring muscle thickness represents a suitable method for determining muscle
      function in patients with acute aSAH, because the disordered consciousness often
      experienced during the acute phase causes active movement to be difficult for
      these patients. Objectives We investigated changes in quadriceps muscle thickness
      in patients with aneurysmal subarachnoid hemorrhage to determine whether muscle
      dysfunction during the acute phase relates to (or predicts) the outcome of aSAH.
      Methods Seventeen patients with aSAH (mean age = 66 +/- 11, men/women = 4/13)
      were enrolled, and their quadriceps muscle thickness measured
      ultrasonographically upon admission and again 2 weeks later. Results Quadriceps
      muscle thickness significantly decreased from admission (mean = 3.00 +/- 0.72 cm)
      to the second measurement (2.67 +/- 0.74 cm, p = 0.001). The relative differences
      in quadriceps muscle thickness were correlated with the Hunt and Hess grade (r = 
      0.72, p = 0.001) and the modified Rankin Scale score at 90 days (r = -0.78, p =
      0.0002). Conclusions Our results indicate that quadriceps muscle thickness
      decreases in patients with acute aneurysmal subarachnoid hemorrhage, particularly
      in patients with poor Hunt and Hess grade or marked disability.

PMID- 29216793
TI  - Parametric study of patient-specific femoral locking plates based on a combined
      musculoskeletal multibody dynamics and finite element modeling.
AB  - A combined musculoskeletal multibody dynamics and finite element modeling was
      performed to investigate the effects of design parameters on the fracture-healing
      efficiency and the mechanical property of a patient-specific anatomically
      adjusted femoral locking plate. Specifically, the screw type, the thickness and
      material of the locking plate, the gap between two femoral fragments (fracture
      gap) and the distance between bone and plate (interface gap) were evaluated
      during a human walking. We found that the patient-specific locking plate
      possessed greater mechanical strength and more efficient fracture healing than
      the corresponding traditional plate. An optimal patient-specific femoral locking
      plate would consist of bicortical locking screws, Ti-6Al-4V material and 4.75-mm
      plate thickness with a fracture gap of 2 mm and an interface gap of 1 mm. The
      developed patient-specific femoral locking plate based on the patient-specific
      musculoskeletal mechanical environment was more beneficial to fracture
      rehabilitation and healing. The patient-specific design method provides an
      effective research platform for designing and optimizing the patient-specific
      femoral locking plate under realistic in vivo walking conditions, which can be
      extended to the design of other implants as well as to other physiological
      loading conditions related to various daily activities.

PMID- 29216794
TI  - Fragmented QRS complexes are associated with left ventricular dysfunction in
      patients with type-2 diabetes mellitus: a two-dimensional speckle tracking
      echocardiography study.
AB  - BACKGROUND: Heart failure may develop independently of coronary artery disease in
      diabetes mellitus (DM) patients. Fragmented QRS (fQRS) is a marker of myocardial
      fibrosis or scar tissue and is related to an increase in cardiovascular adverse
      events. In this study, we examined the utility of speckle tracking
      echocardiography (STE) in assessing LV function in DM patients with fQRS. METHODS
      AND RESULTS: The current study included 178 consecutive patients diagnosed with
      type-2 DM. The patients included were separated into two groups: those with (n =
      50) and without (n = 128) fQRS. The two groups were compared by obtaining LV
      strain values with STE. Statistically significant differences were also
      identified between fQRS(-) and fQRS (+) groups with respect to Lv-GLS (p < .001),
      maxLAVI (p = .020), minLAVI (p < .001), E velocity (p < .001), Em velocity
      (0.002), E/Em ratio (<0.001) SRe (p < .001), SRe/SRa ratio (p < .001), SRivr (p <
      .001) and E/SRivr ratio (p < .001). In the multiple linear regression analysis,
      fQRS (beta = -2.077, p = .002) and DM duration (beta = -0.216, p = .021) were
      identified as independent predictors of Lv-GLS. However, fQRS (beta = 4.557, p =
      .001) and minLAVI (beta = -2.198, p = .031) were also found to be independent
      predictors of E/SRivr. We also performed multiple logistic regression analysis
      and identified Lv-GLS (beta = -0.557, p = .001), minLAVI (beta = -0.769, p =
      .001), E/Em ratio (beta = 0.650, p = .001) and E/SRivr (beta = 0.105, p = .001)
      as independent predictors of fQRS. Conclusions: The results of this study
      revealed that subclinical LV dysfunction was more common in diabetic patients
      with fQRS. Therefore, determination of fQRS could be an indicator of the diabetic
      CMP in patients with DM.

PMID- 29216795
TI  - Oxidative Stress And Prolidase Enzyme Activity In The Pathogenesis Of Primary
      Varicose Veins.
AB  - Objectives Vascular endothelial dysfunction leads to the emerging of free oxygen
      radicals, deficiency of antioxidant system, forming of oxidative stress,
      inflammatory processes and release of proinflammatory cytokines. These things
      play big role in the development of primary varicose veins. Prolidase has been
      reported as an indicator of oxidative stress in diabetes, diabetic neuropathy,
      non-ulcerous dyspepsia, osteoporosis, polycystic over syndrome and many other
      diseases. The aim of this study is to evaluate the oxidative stress at venous
      insufficiency and to provide preliminary knowledge about the role of prolidase
      enzyme in varicose vein formation. Methods Ninety patients aged between 22 and 80
      (47.35 +/- 17.69) were included in the study and divided into 3 groups.
      Group1(n:30)(Serum control group): Patients without venous insufficiency. Group
      2(n:30)(Tissue control group(healthy vein group): Patients underwent coronary
      artery bypass surgery (the remaining portion of great saphenous vein used as
      coronary artery bypass graft used as normal tissue) . Group 3(n:30)(Varicose vein
      group): Patients underwent varicose vein surgery (varicose vein and serum of
      these patients were used for study). Total Oxidant Status (TOS), Total
      Antioxidant Status (TAS), Oxidative Stress Index (OSI) and Prolidase enzyme
      levels were detected in tissue and serum samples. Results No significant changes
      were detected between three groups' serum samples in oxidative stress parameters
      and in the prolidase enzyme activity. The tissue TOS and OSI were higher in
      varicose vein group according to normal vein group and this was found
      statistically significant. And TAC levels in varicose vein group were
      significantly lower than normal vein group. Prolidase enzyme activity in varicose
      vein group was found higher according to normal vein group. Conclusion Oxidative
      stress plays a role at the development of primary varicose veins at biochemical
      level. Prolidase enzyme related with oxidative stress may play an important role
      in the pathogenesis of primary varicose veins.

PMID- 29216797
TI  - Mandibular condylar dimensions: Correlation between 3D tomography and dried skull
      measurements.
AB  - Objective Compare the anatomical dimensions of mandibular condyles with the same
      CBCT measurements. Methods Four landmarks were identified on the condyles of
      dried skulls and are measured with their corresponding areas in CBCT images:
      Right Width of Condyle (RW), Left Width of Condyle (LW), Right Length of Condyle
      (RL), and Left Length of Condyle (LL). Results With respect to direct
      measurements on the dry skulls, statistically significant differences were found
      between sexes (p < 0.001). When the real values were compared with the CBCT, it
      was observed that the bias depends on the magnitude of the measurement. It means
      that there is an underestimation for smaller values and an overestimation for
      larger values. Conclusion CBCT is reliable imaging modality, but when compared
      real measures of condyle length are more reliable then width.

PMID- 29216798
TI  - Associations Between Objectively Measured Physical Activity and Executive
      Functioning in Young Adults.
AB  - Associations between daily physical activity (PA) and executive functioning have
      rarely been investigated among young adults. This study examined these
      associations among 162 university students (74 females and 88 males; mean age =
      19.0, SD = 1.1 years). We measured PA objectively, using hip-mounted
      accelerometers, and assessed executive functioning in a task-switching paradigm.
      Anthropometrics measurements were gathered using standardized procedures. Through
      linear regression modeling, we found moderate-to-vigorous physical activity (beta
      = -0.19, 95% CI = [-0.35, -0.03], p = .02) and light physical activity (beta = 
      0.17, 95% CI = [-0.34, -0.01], p = .04) to be associated with smaller global
      reaction time switch costs. Total PA was not associated with task-switching
      performance, and there were no statistically significant associations between PA
      indicators and local switch costs. As both moderate-to-vigorous and light
      physical activities were associated with better executive function in young
      adults, there can be important cognitive benefits to remaining physically active.

PMID- 29216799
TI  - Flavonoids as potent allosteric inhibitors of protein tyrosine phosphatase 1B:
      molecular dynamics simulation and free energy calculation.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a member of the PTP superfamily which
      is considered to be a negative regulator of insulin receptor (IR) signaling
      pathway. PTP1B is a promising drug target for the treatment of type 2 diabetes,
      obesity, and cancer. The existence of allosteric site in PTP1B has turned the
      researcher's attention to an alternate strategy for inhibition of this enzyme.
      Herein, the molecular interactions between the allosteric site of PTP1B with
      three non-competitive flavonoids, (MOR), (MOK), and (DPO) have been investigated.
      Three ligands were docked into allosteric site of the enzyme. The resulting
      protein-ligand complexes were used for molecular dynamics studies. Principal
      component and free-energy landscape (FEL) as well as cluster analyses were used
      to investigate the conformational and dynamical properties of the protein and
      identify representative enzyme substrates bounded to the inhibitors. Per residue
      energy decomposition analysis attributed dissimilar affinities of three
      inhibitors to the several hydrogen bonds and non-bonded interactions. In
      conclusion, our results exhibited an inhibitory pattern of the ligands against
      PTP1B.

PMID- 29216800
TI  - Vascular Ehlers-Danlos Syndrome With a Novel Missense COL3A1 Mutation Present
      With Pulmonary Complications and Iliac Arterial Dissection.
AB  - Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue
      disorder due to its high tendency of arterial and organ rupture. Pulmonary
      complications in vEDS are rare. We present a young male patient with vEDS who
      developed severe pulmonary complications and severe rupture of the iliac artery
      at different stages of his life. Vascular Ehlers-Danlos syndrome was diagnosed
      based on clinical manifestations and confirmed by the identification of COL3A1
      gene mutation. Due to high bleeding tendency and weak cardiopulmonary capacity,
      conservative treatment was taken for him. To our knowledge, this is the first
      report of vEDS case in which the patient developed both pulmonary complications
      and dissection of large arteries. Our report emphasizes the importance of
      considering vEDS when an adolescent develops unexplained pulmonary cysts with
      fragility of lung tissues. Genetic counseling and close monitoring should be
      performed for earlier diagnosis and prevention of severe complications of large
      arteries. The typical presentations of vEDS were also discussed by means of a
      review of case reports on vEDS with pulmonary complications.

PMID- 29216801
TI  - First Report of Prenatal Ascertainment of a Fetus With Homozygous Loss of the
      SOX10 Gene and Phenotypic Correlation by Autopsy Examination.
AB  - The SOX10 gene plays a vital role in neural crest cell development and migration.
      Abnormalities in SOX10 are associated with Waardenburg syndrome Types II and IV,
      and these patients have recognizable clinical features. This case report
      highlights the first ever reported homozygous loss of function of the SOX10 gene
      in a human. This deletion is correlated using family history, prenatal
      ultrasound, microarray analysis of amniotic fluid, and ultimately, a medical
      autopsy examination to further elucidate phenotypic effects of this genetic
      variation. Incorporating the use of molecular pathology into the autopsy
      examination of fetuses with suspected congenital anomalies is vital for
      appropriate family counseling, and with the ability to use formalin-fixed and
      paraffin-embedded tissues, has become a practical approach in autopsy pathology.

PMID- 29216802
TI  - Martha Wollstein of Babies Hospital in New York City (1868-1939)-The First North
      American Pediatric Pathologist.

PMID- 29216803
TI  - Neutrophil-mediated delivery of nanotherapeutics across blood vessel barrier.
AB  - Nanotherapeutics, nanoparticles (NPs) loaded with drugs, show the ability of
      tissue targeting, long circulation and low toxicity compared with free drugs.
      Endothelium lying the lumen of a blood vessel is a barrier to restrain tissue
      deposition of nanotherapeutics. Neutrophils, a type of white blood cells, migrate
      across endothelium during inflammation. There is an emerging concept that in situ
      targeting of neutrophils allows delivery of nanotherapeutics into deep tissues at
      disease sites. Here we summarize the recent advances in delivery of
      nanotherapeutics to inflammatory tissues or tumor microenvironments via
      neutrophil infiltration. The studies would shift the current paradigm of
      nanomedicine to biology-driven design of nanotherapeutics. [Formula: see text].

PMID- 29216804
TI  - The use of alpha-fetoprotein for the treatment of autoimmune diseases and cancer.
AB  - Alpha-fetoprotein is a shuttle protein that delivers nutrients through receptor
      mediated endocytosis to embryotic cells. In adults, alpha-fetoprotein can shuttle
      drugs into alpha-fetoprotein receptor-positive myeloid-derived suppressor,
      regenerating and also cancer cells. Drugs with high-binding affinity to alpha
      fetoprotein can activate or deplete targeted cells. Myeloid-derived suppressor
      cells activation leads to immune suppression that can be used for treating
      autoimmune diseases. On the other hand, toxins delivered by alpha-fetoprotein can
      damage myeloid-derived suppressor cells and consequently unleash innate and
      adaptive immunity to destroy cancer cells. Innate immunity natural killers reduce
      cancer stem cells and metastases. The new alpha-fetoprotein drug noncovalent
      complexes for immunotherapy change the local immune balance and has potential in
      oncology, autoimmune and infectious diseases treatment, inflammation,
      transplantation, vaccination, etc.

PMID- 29216805
TI  - A review on recent technologies for the manufacture of pulmonary drugs.
AB  - This review discusses recent developments in the manufacture of inhalable dry
      powder formulations. Pulmonary drugs have distinct advantages compared with other
      drug administration routes. However, requirements of drugs properties complicate
      the manufacture. Control over crystallization to make particles with the desired
      properties in a single step is often infeasible, which calls for micronization
      techniques. Although spray drying produces particles in the desired size range, a
      stable solid state may not be attainable. Supercritical fluids may be used as a
      solvent or antisolvent, which significantly reduces solvent waste. Future
      directions include application areas such as biopharmaceuticals for dry powder
      inhalers and new processing strategies to improve the control over particle
      formation such as continuous manufacturing with in-line process analytical
      technologies.

PMID- 29216806
TI  - An industry update: the latest developments in therapeutic delivery.
AB  - This industry update covers the period from 1 September through 30 September
      2017, and is based on information sourced from company press releases, scientific
      literature, patents and various news websites. The month saw the US FDA approve
      three new molecular entities, Aliqopa (copanlisib dihydrochloride) (Bayer
      Healthcare); Solosec (secnidazole) (Symbiomix Therapeutics) and Verzenio
      (abemaciclib) (Eli Lilly and Co). Intarcia Therapeutics Inc. has its application
      for approval of a novel drug device combination of exenatide for the treatment of
      diabetes rejected by FDA but said that it will work to address the concerns and
      refile the application. The impact of biosimilars in the market is steadily
      increasing with seven biosimilars approved in the USA and Sandoz hoping to add to
      this with its announcement that FDA has accepted its Biologics License
      Application for a biosimilar version of Roche's Rituxan. Circassia announced
      positive top line results of a respiratory drug, Duaklir (for the treatment of
      chronic obstructive pulmonary disease) and Sarepta (for its new treatment for
      Duchenne muscular dystrophy). Axovant Sciences Ltd announced the failure if its
      drug Intepirdine in the treatment of Alzheimer's, adding to a growing list of
      drug failures in this area. There were a number of developments in the area of
      oncology with Bristol-Myers Squibb and Infinity Pharmaceuticals announcing an
      expansion of their collaboration looking at combination treatments, as well as
      Eli Lilly and Co's approval for Verzenio. Rani Therapeutics and Intra-Cellular
      Therapies announced successful funding rounds to support their drug programs.
      Allergan announced a novel licensing deal for its dry eye drug, Restasis, which
      it hopes would allow it to stave off patent challenges from several companies
      looking to develop generic versions of the drug. New research suggests that loss
      of sense of smell can be linked to an increased risk of developing Parkinson's
      disease.

PMID- 29216807
TI  - Ultrasound-triggered liposomes for on-demand local anesthesia.

PMID- 29216808
TI  - Welcome to volume 9 of Therapeutic Delivery.
AB  - Happy New Year to all of our readers! Welcome to volume 9 of Therapeutic
      Delivery. We would like to take the opportunity to look back over 2017, which was
      another excellent year for us. We thank all our readers, reviewers, authors and
      Editorial Board members for their continued support and very much look forward to
      working with all our contributors again in 2018.

PMID- 29216809
TI  - The Transliminal Self: The Ebb and Flow of the Kidney Transplant Experience.
AB  - For people with kidney disease, transplantation is considered a better treatment
      option than dialysis. A kidney transplant does not, however, ensure an illness
      free existence. Compared with the wealth of literature produced from a biomedical
      perspective, there is little qualitative research focused on the young adult
      transplant experience. This article presents the findings of a phenomenological
      study exploring young adults' kidney transplant experiences. Using a qualitative
      phenomenological approach, semidirected interviews were conducted with five
      people. Analysis of the transcribed interviews revealed that these individuals'
      kidney transplant experiences were paradoxical in nature: Participants described
      an existence between sickness and health, self and other, life and death.
      Consequently, liminality was identified as one of the experience's key elements
      and used together with the concept of rites of passage in its analysis. To
      incorporate these experiences, the term transliminal self is proposed.

PMID- 29216810
TI  - Effects of Valence on Hemispheric Specialization for Emotion Word Processing.
AB  - The use of emotion in language is a key element of human interactions and a rich
      area for cognitive research. The present study examined reactions to words of
      five types: positive emotion (e.g., happiness), negative emotion (e.g., hatred),
      positive emotion-laden (e.g., blessing), negative emotion-laden (e.g., prison),
      and neutral (e.g., chance). Words and nonwords were intermixed in a lexical
      decision task using hemifield presentation. Results revealed a general left
      hemisphere advantage. Overall, reaction times for positive words were faster than
      for negative or neutral words and this effect varied by hemifield of
      presentation. These results support a valence hypothesis of specialized
      processing in the left hemisphere of the brain for positive emotions and the
      right hemisphere for negative emotions.

PMID- 29216811
TI  - Phrase Lengths and the Perceived Informativeness of Prosodic Cues in Turkish.
AB  - It is known from previous studies that in many cases (though not all) the
      prosodic properties of a spoken utterance reflect aspects of its syntactic
      structure, and also that in many cases (though not all) listeners can benefit
      from these prosodic cues. A novel contribution to this literature is the Rational
      Speaker Hypothesis (RSH), proposed by Clifton, Carlson and Frazier. The RSH
      maintains that listeners are sensitive to possible reasons for why a speaker
      might introduce a prosodic break: "listeners treat a prosodic boundary as more
      informative about the syntax when it flanks short constituents than when it
      flanks longer constituents," because in the latter case the speaker might have
      been motivated solely by consideration of optimal phrase lengths. This would
      effectively reduce the cue value of an appropriately placed prosodic boundary. We
      present additional evidence for the RSH from Turkish, a language typologically
      different from English. In addition, our study shows for the first time that the
      RSH also applies to a prosodic break which conflicts with the syntactic
      structure, reducing its perceived cue strength if it might have been motivated by
      length considerations. In this case, the RSH effect is beneficial. Finally, the
      Turkish data show that prosody-based explanations for parsing preferences such as
      the RSH do not take the place of traditional syntax-sensitive parsing strategies
      such as Late Closure. The two sources of guidance co-exist; both are used when
      available.

PMID- 29216812
TI  - Separability of Tones and Rhymes in Chinese Speech Perception: Evidence from
      Perceptual Migrations.
AB  - This study used the perceptual-migration paradigm to explore whether Mandarin
      tones and syllable rhymes are processed separately during Mandarin speech
      perception. Following the logic of illusory conjunctions, we calculated the cross
      ear migration of tones, rhymes, and their combination in Chinese and English
      listeners. For Chinese listeners, tones migrated more than rhymes. For English
      listeners, the opposite pattern was found. The results lend empirical support to
      autosegmental theory, which claims separability and mobility between tonal and
      segmental representations. They also provide evidence that such representations
      and their involvement in perception are deeply shaped by a listener's linguistic
      experience.

PMID- 29216813
TI  - Processing Relationships Between Language-Being-Spoken and Other Speech
      Dimensions in Monolingual and Bilingual Listeners.
AB  - While indexical information is implicated in many levels of language processing,
      little is known about the internal structure of the system of indexical
      dimensions, particularly in bilinguals. A series of three experiments using the
      speeded classification paradigm investigated the relationship between various
      indexical and non-linguistic dimensions of speech in processing. Namely, we
      compared the relationship between a lesser-studied indexical dimension relevant
      to bilinguals, which language is being spoken (in these experiments, either
      Mandarin Chinese or English), with: talker identity (Experiment 1), talker gender
      (Experiment 2), and amplitude of speech (Experiment 3). Results demonstrate that
      language-being-spoken is integrated in processing with each of the other
      dimensions tested, and that these processing dependencies seem to be independent
      of listeners' bilingual status or experience with the languages tested. Moreover,
      the data reveal processing interference asymmetries, suggesting a processing
      hierarchy for indexical, non-linguistic speech features.

PMID- 29216815
TI  - Introduction.

PMID- 29216814
TI  - Editorial.

PMID- 29216816
TI  - Acute kidney injury in low- and middle-income countries: investigations,
      management and prevention.
AB  - Acute kidney injury (AKI) is a relatively common condition, encountered in
      everyday paediatric clinical practice. It is an important cause of morbidity and
      mortality in children both inside and outside intensive care units. It is
      associated with prolonged hospital stay and progression to chronic kidney
      disease. The burden of AKI is particularly high in low- and middle-income
      countries where rural areas and smaller cities in the countryside predominate.
      Most of these areas suffer from poverty, poor sanitation, water quality and
      hygiene, lack of education and poor access to health care. AKI is preventable if
      it is detected sufficiently early and managed promptly. Improved nephrology
      services and the availability of cost-effective dialysis facilities in resource
      limited settings should reduce morbidity and save many children's lives.

PMID- 29216817
TI  - Characterization of sulfhydryl oxidase from Aspergillus tubingensis.
AB  - BACKGROUND: Despite of the presence of sulfhydryl oxidases (SOXs) in the
      secretomes of industrially relevant organisms and their many potential
      applications, only few of these enzymes have been biochemically characterized. In
      addition, basic functions of most of the SOX enzymes reported so far are not
      fully understood. In particular, the physiological role of secreted fungal SOXs
      is unclear. RESULTS: The recently identified SOX from Aspergillus tubingensis
      (AtSOX) was produced, purified and characterized in the present work. AtSOX had a
      pH optimum of 6.5, and showed a good pH stability retaining more than 80% of the
      initial activity in a pH range 4-8.5 within 20 h. More than 70% of the initial
      activity was retained after incubation at 50  degrees C for 20 h. AtSOX contains
      a non-covalently bound flavin cofactor. The enzyme oxidised a sulfhydryl group of
      glutathione to form a disulfide bond, as verified by nuclear magnetic resonance
      spectroscopy. AtSOX preferred glutathione as a substrate over cysteine and
      dithiothreitol. The activity of the enzyme was totally inhibited by 10 mM zinc
      sulphate. Peptide- and protein-bound sulfhydryl groups in bikunin, gliotoxin,
      holomycin, insulin B chain, and ribonuclease A, were not oxidised by the enzyme.
      Based on the analysis of 33 fungal genomes, SOX enzyme encoding genes were found
      close to nonribosomal peptide synthetases (NRPS) but not with polyketide
      synthases (PKS). In the phylogenetic tree, constructed from 25 SOX and
      thioredoxin reductase sequences from IPR000103 InterPro family, AtSOX was
      evolutionary closely related to other Aspergillus SOXs. Oxidoreductases involved
      in the maturation of nonribosomal peptides of fungal and bacterial origin, namely
      GliT, HlmI and DepH, were also evolutionary closely related to AtSOX whereas
      fungal thioreductases were more distant. CONCLUSIONS: AtSOX (55 kDa) is a fungal
      secreted flavin-dependent enzyme with good stability to both pH and temperature.
      A Michaelis-Menten behaviour was observed with reduced glutathione as a
      substrate. Based on the location of SOX enzyme encoding genes close to NRPSs,
      SOXs could be involved in the secondary metabolism and act as an accessory enzyme
      in the production of nonribosomal peptides.

PMID- 29216818
TI  - Neuroprotective effects of amiodarone in a mouse model of ischemic stroke.
AB  - BACKGROUND: Ion channels play a crucial role in the development of ischemic brain
      injury. Recent studies have reported that the blockade of various types of ion
      channels improves outcomes in experimental stroke models. Amiodarone, one of the
      most effective drugs for life-threatening arrhythmia, works as a multiple channel
      blocker and its characteristics cover all four Vaughan-Williams classes. Although
      it is known that amiodarone indirectly contributes to preventing ischemic stroke
      by maintaining sinus rhythm in patients with atrial fibrillation, the direct
      neuroprotective effect of amiodarone has not been clarified. The purpose of this
      study was to investigate the direct effect of amiodarone on ischemic stroke in
      mice. METHODS: Focal cerebral ischemia was induced via distal permanent middle
      cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment
      group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post
      treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the
      control group received vehicle only. In addition, the sodium channel opener
      veratrine and selective beta-adrenergic agonist isoprotelenol were used to
      elucidate the targeted pathway. Heart rate and blood pressure were monitored
      perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body
      asymmetry test and the corner test were used for neurological evaluation.
      RESULTS: Amiodarone pre-treatment and post-treatment reduced the heart rate but
      did not affect the blood pressure. No mice showed arrhythmia. Compared with the
      control group, the amiodarone pre-treatment group had smaller infarct volumes
      (8.9 +/- 2.1% hemisphere [mean +/- SD] vs. 11.2 +/- 1.4%; P < 0.05) and improved
      functional outcomes: lower asymmetric body swing rates (52 +/- 17% vs. 65 +/-
      18%; P < 0.05) and fewer left turns (7.1 +/- 1.2 vs. 8.3 +/- 1.2; P < 0.05). In
      contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The
      neuroprotective effect of amiodarone pre-treatment was abolished by co
      administration of veratrine but not by isoproterenol. CONCLUSIONS: Amiodarone pre
      treatment attenuated ischemic brain injury and improved functional outcomes
      without affecting heart rhythm and blood pressure. The present results showed
      that amiodarone pre-treatment has neuroprotective effects, at least in part, via
      blocking the sodium channels.

PMID- 29216819
TI  - Transcriptomic analysis of Pak Choi under acute ozone exposure revealed
      regulatory mechanism against ozone stress.
AB  - BACKGROUND: Ground-level ozone (O3) is one of the major air pollutants, which
      cause oxidative injury to plants. The physiological and biochemical mechanisms
      underlying the responses of plants to O3 stress have been well investigated.
      However, there are limited reports about the molecular basis of plant responses
      to O3. In this study, a comparative transcriptomic analysis of Pak Choi (Brassica
      campestris ssp. chinensis) exposed to different O3 concentrations was conducted
      for the first time. RESULTS: Seedlings of Pak Choi with five leaves were exposed
      to non-filtered air (NF, 31 ppb) or elevated O3 (E-O3, 252 ppb) for 2 days (8 h
      per day, from 9:00-17:00). Compared with plants in the NF, a total of 675
      differentially expressed genes (DEGs) were identified in plants under E-O3,
      including 219 DEGs with decreased expressions and 456 DEGs with increased
      expressions. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed
      that O3 stress invoked multiple cellular defense pathways to mitigate the
      impaired cellular integrity and metabolism, including 'glutathione metabolism',
      'phenylpropanoid biosynthesis', 'sulfur metabolism', 'glucosinolate
      biosynthesis', 'cutin, suberine and wax biosynthesis' and others. Transcription
      factors potentially involved in this cellular regulation were also found, such as
      AP2-ERF, WRKY, JAZ, MYB etc. Based on the RNA-Seq data and previous studies, a
      working model was proposed integrating O3 caused reactive oxygen burst, oxidation
      reduction regulation, jasmonic acid and downstream functional genes for the
      regulation of cellular homeostasis after acute O3 stress. CONCLUSION: The present
      results provide a valuable insight into the molecular responses of Pak Choi to
      acute O3 stress and the specific DEGs revealed in this study could be used for
      further functional identification of key allelic genes determining the O3
      sensitivity of Pak Choi.

PMID- 29216820
TI  - Comparison of the effect of different infusion rates of sufentanil on surgical
      stress index during cranial pinning in children under general anaesthesia: a
      randomized controlled study.
AB  - BACKGROUND: Surgical stress index (SSI) is an established indicator for
      intraoperative nociception. Opioids are used to block stimulus of cranial pinning
      in neurosurgery. We investigated the effect of different infusion rates of
      sufentanil on SSI during cranial pinning in children under general anaesthesia.
      METHODS: Forty-nine children (2-12 years of age) underwent neurosurgery with
      pinning. The children were randomized into three groups based on the rate of
      sufentanil infusion: 0.2, 0.5, and 0.8 MUg.kg-1.hr.-1. Continuous sufentanil
      infusion began following neuromuscular blockade administration, at a rate
      determined by each patient's assigned treatment group. Following preparation for
      surgery, cranial pinning was performed. Systolic, diastolic, and mean blood
      pressures, along with heart rate and photoplethysmographic data, were
      continuously recorded from 1 min prior to cranial pinning through 5 min after
      cranial pinning, in 1-min intervals. SSI was calculated following the completion
      of surgery. Differences in measured outcomes over time among the three groups
      were evaluated using a generalized estimation equation. Differences in pinning
      outcomes in the same group were evaluated with Freidman test. RESULTS: We found
      no statistical differences in long-term SSI that were associated with different
      infusion rates of sufentanil during cranial pinning. Blood pressures in all
      groups increased for 2 min after cranial pinning, and then decreased; we found no
      statistical difference in long-term blood pressure values among the groups. Heart
      rate increased after pinning in the group that received a low-dose infusion of
      sufentanil. CONCLUSIONS: Since SSI was intended to measure the blunting effects
      of sufentanil towards the noxious stimulus of cranial pinning, our results
      suggest that SSI might not be sufficiently sensitive to monitor the nociceptive
      response in children. TRIAL REGISTRATION: ( KCT0000978 , Jan-07, 2014).

PMID- 29216822
TI  - Bayesian estimation of scaled mutation rate under the coalescent: a sequential
      Monte Carlo approach.
AB  - BACKGROUND: Samples of molecular sequence data of a locus obtained from random
      individuals in a population are often related by an unknown genealogy. More
      importantly, population genetics parameters, for instance, the scaled population
      mutation rate Theta=4N e MU for diploids or Theta=2N e MU for haploids (where N e
      is the effective population size and MU is the mutation rate per site per
      generation), which explains some of the evolutionary history and past qualities
      of the population that the samples are obtained from, is of significant interest.
      RESULTS: In this paper, we present the evolution of sequence data in a Bayesian
      framework and the approximation of the posterior distributions of the unknown
      parameters of the model, which include Theta via the sequential Monte Carlo (SMC)
      samplers for static models. Specifically, we approximate the posterior
      distributions of the unknown parameters with a set of weighted samples i.e., the
      set of highly probable genealogies out of the infinite set of possible
      genealogies that describe the sampled sequences. The proposed SMC algorithm is
      evaluated on simulated DNA sequence datasets under different mutational models
      and real biological sequences. In terms of the accuracy of the estimates, the
      proposed SMC method shows a comparable and sometimes, better performance than the
      state-of-the-art MCMC algorithms. CONCLUSIONS: We showed that the SMC algorithm
      for static model is a promising alternative to the state-of-the-art approach for
      simulating from the posterior distributions of population genetics parameters.

PMID- 29216821
TI  - Molecular targets and signaling pathways regulated by nuclear translocation of
      syndecan-1.
AB  - BACKGROUND: The cell-surface heparan sulfate proteoglycan syndecan-1 is important
      for tumor cell proliferation, migration, and cell cycle regulation in a broad
      spectrum of malignancies. Syndecan-1, however, also translocates to the cell
      nucleus, where it might regulate various molecular functions. RESULTS: We used a
      fibrosarcoma model to dissect the functions of syndecan-1 related to the nucleus
      and separate them from functions related to the cell-surface. Nuclear
      translocation of syndecan-1 hampered the proliferation of fibrosarcoma cells
      compared to the mutant lacking nuclear localization signal. The growth inhibitory
      effect of nuclear syndecan-1 was accompanied by significant accumulation of cells
      in the G0/G1 phase, which indicated a possible G1/S phase arrest. We implemented
      multiple, unsupervised global transcriptome and proteome profiling approaches and
      combined them with functional assays to disclose the molecular mechanisms that
      governed nuclear translocation and its related functions. We identified genes and
      pathways related to the nuclear compartment with network enrichment analysis of
      the transcriptome and proteome. The TGF-beta pathway was activated by nuclear
      syndecan-1, and three genes were significantly altered with the deletion of
      nuclear localization signal: EGR-1 (early growth response 1), NEK11 (never-in
      mitosis gene a-related kinase 11), and DOCK8 (dedicator of cytokinesis 8). These
      candidate genes were coupled to growth and cell-cycle regulation. Nuclear
      translocation of syndecan-1 influenced the activity of several other
      transcription factors, including E2F, NFkappabeta, and OCT-1. The transcripts and
      proteins affected by syndecan-1 showed a striking overlap in their corresponding
      biological processes. These processes were dominated by protein phosphorylation
      and post-translation modifications, indicative of alterations in intracellular
      signaling. In addition, we identified molecules involved in the known functions
      of syndecan-1, including extracellular matrix organization and transmembrane
      transport. CONCLUSION: Collectively, abrogation of nuclear translocation of
      syndecan-1 resulted in a set of changes clustering in distinct patterns, which
      highlighted the functional importance of nuclear syndecan-1 in hampering cell
      proliferation and the cell cycle. This study emphasizes the importance of the
      localization of syndecan-1 when considering its effects on tumor cell fate.

PMID- 29216823
TI  - Historical isolation and contemporary gene flow drive population diversity of the
      brown alga Sargassum thunbergii along the coast of China.
AB  - BACKGROUND: Long-term survival in isolated marginal seas of the China coast
      during the late Pleistocene ice ages is widely believed to be an important
      historical factor contributing to population genetic structure in coastal marine
      species. Whether or not contemporary factors (e.g. long-distance dispersal via
      coastal currents) continue to shape diversity gradients in marine organisms with
      high dispersal capability remains poorly understood. Our aim was to explore how
      historical and contemporary factors influenced the genetic diversity and
      distribution of the brown alga Sargassum thunbergii, which can drift on surface
      water, leading to long-distance dispersal. RESULTS: We used 11 microsatellites
      and the plastid RuBisCo spacer to evaluate the genetic diversity of 22 Sargassum
      thunbergii populations sampled along the China coast. Population structure and
      differentiation was inferred based on genotype clustering and pairwise F ST and
      allele-frequency analyses. Integrated genetic analyses revealed two genetic
      clusters in S. thunbergii that dominated in the Yellow-Bohai Sea (YBS) and East
      China Sea (ECS) respectively. Higher levels of genetic diversity and variation
      were detected among populations in the YBS than in the ECS. Bayesian coalescent
      theory was used to estimate contemporary and historical gene flow. High levels of
      contemporary gene flow were detected from the YBS (north) to the ECS (south),
      whereas low levels of historical gene flow occurred between the two regions.
      CONCLUSIONS: Our results suggest that the deep genetic divergence in S.
      thunbergii along the China coast may result from long-term geographic isolation
      during glacial periods. The dispersal of S. thunbergii driven by coastal currents
      may facilitate the admixture between southern and northern regimes. Our findings
      exemplify how both historical and contemporary forces are needed to understand
      phylogeographical patterns in coastal marine species with long-distance
      dispersal.

PMID- 29216824
TI  - Use of a mixed culture strategy to isolate halophilic bacteria with antibacterial
      and cytotoxic activity from the Manaure solar saltern in Colombia.
AB  - BACKGROUND: Water evaporation in solar salterns creates salinity gradients that
      promote the adaptation of microbial species to different salinities. This
      competitive habitat challenges the metabolic capabilities of microorganisms and
      promotes alterations in their production of secondary metabolites. Thus, solar
      salterns are a potentially important source of new natural products. In Colombia,
      the most important and representative solar saltern is located in Manaure (La
      Guajira) in the north of Colombia. The aim of this study was to develop an
      alternative screening strategy to select halophilic bacteria as producers of
      bioactive compounds from mixed microbial cultures rather than individual
      environmental isolates. Brine and sediment samples from different ponds (across a
      salinity gradient) were inoculated in seven different culture media to grow
      bacteria and archaea, allowing for a total of 40 different mixed cultures. An
      organic extract from each mixed culture was obtained and tested against multidrug
      resistant pathogens, including Klebsiella pneumoniae, vancomycin-resistant
      Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Bacillus
      subtilis. In addition, the extracts were tested against two human cancer cell
      lines, cervical adenocarcinoma (SiHa) and lung carcinoma (A-549). RESULTS: Twenty
      four of the forty extracts from mixed cultures obtained from brine and sediment
      samples from the Manaure solar saltern showed antibacterial activity against
      Bacillus subtilis. Two extracts, referred to as A1SM3-29 and A1SM3-36, were also
      active against a methicillin-resistant Staphylococcus aureus, with the latter
      extract also showing slight cytotoxic activity against the assayed human lung
      cancer cell line. From this mixed culture, nine isolates were cultivated, and
      their extracts were tested against the same pathogens, resulting in the
      identification of a Vibrio sp. strain (A1SM3-36-8) with antimicrobial activity
      that was similar to that observed for the mixed culture extract. The extract of
      this strain was subjected to a bioautography assay, and 3 different fractions
      exhibited antibacterial activity against methicillin-resistant Staphylococcus
      aureus. Based on the amount obtained for each fraction, F3 was selected to
      isolate and identify its metabolites. The major compound was identified by NMR
      and HRMS as 13-cis-docosenamide, an amide that has been previously reported to be
      an antimicrobial and cytotoxic compound. CONCLUSIONS: Our results shows the
      utility of our strategy in detecting bioactive molecules in initial mixed
      cultures by biological assays, resulting in the isolation and characterization of
      Vibrio sp. A1SM3-36-8, a halophilic strain with great antibacterial and cytotoxic
      potential.

PMID- 29216825
TI  - Correction to: Generation of expressed sequence tags for discovery of genes
      responsible for floral traits of Chrysanthemum morifolium by next-generation
      sequencing technology.
AB  - After publication of the original article [1] the authors noted that the
      following errors had occurred.

PMID- 29216826
TI  - 6S RNA plays a role in recovery from nitrogen depletion in Synechocystis sp. PCC
      6803.
AB  - BACKGROUND: The 6S RNA is a global transcriptional riboregulator, which is
      exceptionally widespread among most bacterial phyla. While its role is well
      characterized in some heterotrophic bacteria, we subjected a cyanobacterial
      homolog to functional analysis, thereby extending the scope of 6S RNA action to
      the special challenges of photoautotrophic lifestyles. RESULTS: Physiological
      characterization of a 6S RNA deletion strain (DeltassaA) demonstrates a delay in
      the recovery from nitrogen starvation. Significantly decelerated phycobilisome
      reassembly and glycogen degradation are accompanied with reduced photosynthetic
      activity compared to the wild type. Transcriptome profiling further revealed that
      predominantly genes encoding photosystem components, ATP synthase, phycobilisomes
      and ribosomal proteins were negatively affected in DeltassaA. In vivo pull-down
      studies of the RNA polymerase complex indicated that the presence of 6S RNA
      promotes the recruitment of the cyanobacterial housekeeping sigma factor SigA,
      concurrently supporting dissociation of group 2 sigma factors during recovery
      from nitrogen starvation. CONCLUSIONS: The combination of genetic, physiological
      and biochemical studies reveals the homologue of 6S RNA as an integral part of
      the cellular response of Synechocystis sp. PCC 6803 to changing nitrogen
      availability. According to these results, 6S RNA supports a rapid acclimation to
      changing nitrogen supply by accelerating the switch from group 2 sigma factors
      SigB, SigC and SigE to SigA-dependent transcription. We therefore introduce the
      cyanobacterial 6S RNA as a novel candidate regulator of RNA polymerase sigma
      factor recruitment in Synechocystis sp. PCC 6803. Further studies on mechanistic
      features of the postulated interaction should shed additional light on the
      complexity of transcriptional regulation in cyanobacteria.

PMID- 29216828
TI  - Factors necessary for independent walking in patients with thalamic hemorrhage.
AB  - BACKGROUND: Thalamic hemorrhages cause motor paralysis, sensory impairment, and
      cognitive dysfunctions, all of which may significantly affect walking
      independence. We examined the factors related to independent walking in patients
      with thalamic hemorrhage who were admitted to a rehabilitation hospital. METHODS:
      We evaluated 128 patients with thalamic hemorrhage (75 men and 53 women; age
      range, 40-93 years) who were admitted to our rehabilitation hospital. The mean
      duration from symptom onset to rehabilitation hospital admission was 27.2 +/-
      10.3 days, and the mean rehabilitation hospital stay was 71.0 +/- 31.4 days.
      Patients' neurological and cognitive functions were examined with the National
      Institutes of Health Stroke Scale (NIHSS) and Mini-Mental State Examination
      (MMSE), respectively. The relationship between patients' scores on these scales
      and their walking ability at discharge from the rehabilitation hospital was
      analyzed. Additionally, a decision-tree analysis was used to create a model for
      predicting independent walking upon referral to the rehabilitation hospital.
      RESULTS: Among the patients, 65 could walk independently and 63 could not. The
      two patient groups were significantly different in terms of age, duration from
      symptom onset to rehabilitation hospital admission, hematoma type, hematoma
      volume, neurological symptoms, and cognitive function. The decision-tree analysis
      revealed that the patient's age, NIHSS score, MMSE score, hematoma volume, and
      presence of ventricular bleeding were factors that could predict independent
      walking. CONCLUSIONS: In patients with thalamic hemorrhage, the neurological
      symptoms, cognitive function, and neuroimaging factors at onset are useful for
      predicting independent walking.

PMID- 29216827
TI  - Comparative genomic analysis of Brevibacterium strains: insights into key genetic
      determinants involved in adaptation to the cheese habitat.
AB  - BACKGROUND: Brevibacterium strains are widely used for the manufacturing of
      surface-ripened cheeses, contributing to the breakdown of lipids and proteins and
      producing volatile sulfur compounds and red-orange pigments. The objective of the
      present study was to perform comparative genomic analyses in order to better
      understand the mechanisms involved in their ability to grow on the cheese surface
      and the differences between the strains. RESULTS: The genomes of 23
      Brevibacterium strains, including twelve strains isolated from cheeses, were
      compared for their gene repertoire involved in salt tolerance, iron acquisition,
      bacteriocin production and the ability to use the energy compounds present in
      cheeses. All or almost all the genomes encode the enzymes involved in ethanol,
      acetate, lactate, 4-aminobutyrate and glycerol catabolism, and in the synthesis
      of the osmoprotectants ectoine, glycine-betaine and trehalose. Most of the
      genomes contain two contiguous genes encoding extracellular proteases, one of
      which was previously characterized for its activity on caseins. Genes encoding a
      secreted triacylglycerol lipase or involved in the catabolism of galactose and D
      galactonate or in the synthesis of a hydroxamate-type siderophore are present in
      part of the genomes. Numerous Fe3+/siderophore ABC transport components are
      present, part of them resulting from horizontal gene transfers. Two cheese
      associated strains have also acquired catecholate-type siderophore biosynthesis
      gene clusters by horizontal gene transfer. Predicted bacteriocin biosynthesis
      genes are present in most of the strains, and one of the corresponding gene
      clusters is located in a probable conjugative transposon that was only found in
      cheese-associated strains. CONCLUSIONS: Brevibacterium strains show differences
      in their gene repertoire potentially involved in the ability to grow on the
      cheese surface. Part of these differences can be explained by different
      phylogenetic positions or by horizontal gene transfer events. Some of the
      distinguishing features concern biotic interactions with other strains such as
      the secretion of proteases and triacylglycerol lipases, and competition for iron
      or bacteriocin production. In the future, it would be interesting to take the
      properties deduced from genomic analyses into account in order to improve the
      screening and selection of Brevibacterium strains, and their association with
      other ripening culture components.

PMID- 29216829
TI  - The role of isolation on contrasting phylogeographic patterns in two cave
      crustaceans.
AB  - BACKGROUND: The underlying mechanisms and processes that prompt the colonisation
      of extreme environments, such as caves, constitute major research themes of
      evolutionary biology and biospeleology. The special adaptations required to
      survive in subterranean environments (low food availability, hypoxic waters,
      permanent darkness), and the geographical isolation of caves, nominate cave
      biodiversity as ideal subjects to answer long-standing questions concerning the
      interplay amongst adaptation, biogeography, and evolution. The present project
      aims to examine the phylogeographic patterns exhibited by two sympatric species
      of surface and cave-dwelling peracarid crustaceans (Asellus aquaticus and
      Niphargus hrabei), and in doing so elucidate the possible roles of isolation and
      exaptation in the colonisation and successful adaptation to the cave environment.
      RESULTS: Specimens of both species were sampled from freshwater hypogean (cave)
      and epigean (surface) habitats in Hungary, and additional data from neighbouring
      countries were sourced from Genbank. Sequencing of mitochondrial and nuclear loci
      revealed, through haplotype network reconstruction (TCS) and phylogenetic
      inference, the genetic structure, phylogeographic patterns, and divergence-time
      estimates of A. aquaticus and N. hrabei surface and cave populations. Contrasting
      phylogeographic patterns were found between species, with A. aquaticus showing
      strong genetic differentiation between cave and surface populations and N. hrabei
      lacking any evidence of genetic structure mediated by the cave environment.
      Furthermore, N. hrabei populations show very low levels of genetic
      differentiation throughout their range, which suggests the possibility of recent
      expansion events over the last few thousand years. CONCLUSIONS: Isolation by cave
      environment, rather than distance, is likely to drive the genetic structuring
      observed between immediately adjacent cave and surface populations of A.
      aquaticus, a predominantly surface species with only moderate exaptations to
      subterranean life. For N. hrabei, in which populations exhibit a fully 'cave
      adapted' (troglomorphic) phenotype, the lack of genetic structure suggests that
      subterranean environments do not pose a dispersal barrier for this surface-cave
      species.

PMID- 29216830
TI  - Factors associated with birth preparedness and complication readiness in Southern
      Ethiopia: a community based cross-sectional study.
AB  - BACKGROUND: Birth preparedness and complication readiness (BP/CR) is a strategy
      to promote use of skilled maternal and neonatal care so that they can get timely
      skilled care, particularly during child birth. There is minimal evidence on the
      factors associated with BP/CR among pregnant women in Ethiopia. Hence, this study
      aimed to assess the factors influencing BP/CR among pregnant women in Southern
      Ethiopia for the purpose of improving utilization of skilled attendant at birth.
      METHODS: A community based cross-sectional study was conducted among 707 pregnant
      women in Southern Ethiopia in March 2015. Both quantitative and qualitative
      methods of data collection were used. For the quantitative study, the study
      subjects were included in the study by employing multi-stage sampling. Data was
      entered into Epidata version 3.1 and analyzed using IBM SPSS statistics 20. Level
      of statistical significance was declared at a p- value of <0.05. For the
      qualitative study, six FGDs were conducted and analyzed based on the thematic
      areas. RESULT: The prevalence of BP /CR in Arba Minch Zuria Woreda was found to
      be 30%. The odds of being prepared for birth and its complications was higher
      among women from high economic class (AOR = 2.29, 95% CI = 1.16, 4.54), with
      frequency of antenatal care(ANC) > = 4 (AOR = 4.52, 95% CI = 2.26, 9.02), who
      received advice on BP &CR (AOR = 1.84, 95% CI = 1.13, 3.01),and who were
      knowledgeable on labor and delivery(LAD) danger signs (AOR = 1.85, 95% CI = 1.01,
      3.44). However, it was lower among women with parity of 2 - 4(AOR = .0.51, 95% CI
      = 0.31, 0.84) and >4 (AOR = 0.51, 95% CI = 0.31, 0.84) than primiparous women. It
      was also lower among women from food insecure households (AOR = 0.26, 95% CI =
      0.16, 0.42) than their counterparts. Lack of awareness on BP/CR, privacy and
      respect in health institutions were mentioned by the FGD discussants as barriers
      to women's preparation for birth. CONCLUSIONS: The study showed that BP/CR is
      inadequate among pregnant women in the study area. Improving socio-economic and
      food security status of women, strengthening community-based education on
      complete attendance of ANC, and conforming to professional ethical standards were
      recommended.

PMID- 29216831
TI  - Validity of mobile electronic data capture in clinical studies: a pilot study in
      a pediatric population.
AB  - BACKGROUND: Clinical studies in children are necessary yet conducting multiple
      visits at study centers remains challenging. The success of "care-at-home"
      initiatives and remote clinical trials suggests their potential to facilitate
      conduct of pediatric studies. This pilot aimed to study the feasibility of
      remotely collecting valid (i.e. complete and correct) saliva samples and clinical
      data utilizing mobile technology. METHODS: Single-center, prospective pilot study
      in children undergoing elective tonsillectomy at the University of Basel
      Children's Hospital. Data on pain scores and concomitant medication and saliva
      samples were collected by caregivers on two to four inpatient study days and on
      three consecutive study days at home. A tailored mobile application developed for
      this study supported data collection. The primary endpoint was the proportion of
      complete and correct caregiver-collected data (pain scale) and saliva samples in
      the at-home setting. Secondary endpoints included the proportion of complete and
      correct saliva samples in the inpatient setting, subjective feasibility for
      caregivers, and study cost. RESULTS: A total number of 23 children were included
      in the study of which 17 children, median age 6.0 years (IQR 5.0, 7.4), completed
      the study. During the at-home phase, 71.9% [CI = 64.4, 78.6] of all caregiver
      collected pain assessments and 53.9% [CI = 44.2, 63.4] of all saliva samples were
      complete and correct. Overall, 64.7% [CI = 58.7, 70.4] of all data collected by
      caregivers at home was complete and correct. The predominant reason for
      incorrectness of data was adherence to the timing of predefined patient actions.
      Participating caregivers reported high levels of satisfaction and willingness to
      participate in similar trials in the future. Study costs for a potential sample
      size of 100 patients were calculated to be 20% lower for the at-home than for a
      traditional in-patient study setting. CONCLUSIONS: Mobile device supported
      studies conducted at home may provide a cost-effective approach to facilitate
      conduct of clinical studies in children. Given findings in this pilot study, data
      collection at home may focus on electronic data capture rather than biological
      sampling.

PMID- 29216832
TI  - A long-surviving patient with advanced esophageal basaloid squamous cell
      carcinoma treated only with radiotherapy: case report and literature review.
AB  - BACKGROUND: Esophageal basaloid squamous cell carcinoma (EBSCC) is a rare
      malignant disease. Advanced EBSCC (AEBSCC) has a poorer prognosis than the more
      common esophageal squamous cell carcinoma, but no treatment policy has yet been
      established. This is the first reported case with AEBSCC treated only with
      radiotherapy. Thus, our long-surviving patient merits consideration. We therefore
      reviewed cases with the same stage of AEBSCC for further investigation. CASE
      PRESENTATION: An 85-year-old man with a chief complaint of difficulty swallowing
      foods was diagnosed with AEBSCC, cT3N1M0, stage III, by thorough examination. The
      basaloid carcinoma extended from the upper thoracic esophagus to the middle
      thoracic esophagus based on imaging studies, endoscopy and biopsy.
      Morphologically, the tumor was an elevated ulcerative area. We conducted
      radiotherapy to relieve symptoms, as the patient and his family refused
      aggressive treatment. He has remained alive without recurrence for 2 years, to
      date, after completing radiotherapy. CONCLUSIONS: Basaloid carcinoma might be
      highly sensitive to radiotherapy. Thus, radiotherapy for local control might be
      beneficial for elderly patients with complications and those refusing aggressive
      treatment.

PMID- 29216833
TI  - Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recently
      identified as a risk factor of gastrointestinal tract cancers, especially
      hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor
      for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to
      determine a potential association between NAFLD and CCA, stratifying by its
      subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). METHODS: A search
      was conducted for relevant studies published up to April 2017 using MEDLINE,
      EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95%
      confidence interval (CI) were estimated using a random-effects model. Subgroup
      analyses were conducted with study characteristics. RESULTS: Seven case-control
      studies were included in the analysis, with a total of 9,102 CCA patients (5,067
      iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an
      increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36-2.79, I 2 =76%). When
      classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of
      2.22 (95%CI: 1.52-3.24, I 2 =67%) and 1.55 (95%CI: 1.03-2.33, I 2 =69%),
      respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41-2.75, I 2
      =71%), 2.09 (95%CI, 1.49-2.91, I 2 =42%) and 2.05 (95%CI, 1.59-2.64, I 2 =0%) for
      all CCAs, iCCA, and eCCA, respectively. CONCLUSIONS: This meta-analysis suggests
      that NAFLD may potentially increase the risk of CCA development. The magnitude of
      NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common
      pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm
      this association are warranted. TRIAL REGISTRATION: The protocol for this study
      was registered with PROSPERO (International Prospective Register of Systematic
      Reviews; no. CRD42016046573).

PMID- 29216834
TI  - Inventory of real world data sources in Parkinson's disease.
AB  - BACKGROUND: Real world data have an important role to play in the evaluation of
      epidemiology and burden of disease; and in assisting health-care decision-makers,
      especially related to coverage and payment decisions. However, there is currently
      no overview of the existing longitudinal real world data sources in Parkinson's
      disease (PD) in the USA. Such an assessment can be very helpful, to support a
      future effort to harmonize real world data collection and use the available
      resources in an optimal way. METHODS: The objective of this comprehensive
      literature review is to systematically identify and describe the longitudinal,
      real world data sources in PD in the USA, and to provide a summary of their
      measurements (categorized into 8 main dimensions: motor and neurological
      functions, cognition, psychiatry, activities of daily living, sleep, quality of
      life, autonomic symptoms and other). The literature search was performed using
      MEDLINE, EMBASE and internet key word search. RESULTS: Of the 53 data sources
      identified between May and August 2016, 16 were still ongoing. Current
      medications (81%) and comorbidities (79%) were frequently collected, in
      comparison to medical imaging (36%), genetic information (30%), caregiver burden
      (11%) and healthcare costs (2%). Many different measurements (n = 108) were
      performed and an interesting variability among used measurements was revealed.
      CONCLUSIONS: Many longitudinal real world data sources on PD exist. Different
      types of measurements have been performed over time. To allow comparison and
      pooling of these multiple data sources, it will be essential to harmonize
      practices in terms of types of measurements.

PMID- 29216835
TI  - Human T-lymphotropic virus 1aA circulation and risk factors for sexually
      transmitted infections in an Amazon geographic area with lowest human development
      index (Marajo Island, Northern Brazil).
AB  - BACKGROUND: This cross-sectional study evaluated the prevalence of infection with
      human T-lymphotropic virus 1 and 2 (HTLV-1 and HTLV-2) in a population from the
      municipalities of Anajas, Chaves, Sao Sebastiao da Boa Vista (SSBV) and Portel in
      the Marajo Archipelago and correlated these data with the epidemiological
      characteristics of the study population. METHODS: A total of 1899 biological
      samples were evaluated. The samples were screened for the presence of anti-HTLV
      antibodies using an enzyme-linked immunosorbent assay (ELISA), and infection was
      confirmed using conventional polymerase chain reaction (PCR), real-time PCR and
      nucleotide sequencing. RESULTS: Eleven samples (0.58%) were seropositive for
      HTLV, but molecular analysis confirmed positivity in only two samples (0.11%).
      Nucleotide sequencing and phylogenetic analysis indicated that the two samples
      positive for HTLV-1 that were isolated in Chaves belonged to the Cosmopolitan
      subtype 1 (HTLV-1a) and Transcontinental subgroup (A). CONCLUSION: Our results
      confirmed the presence of Cosmopolitan Transcontinental HTLV-1 in the Marajo
      Archipelago, Amazon region, and the majority of the population revealed a lack of
      knowledge about sexually transmitted infections, which increases the risk of
      dissemination of HTLV and other agents.

PMID- 29216836
TI  - Key stakeholders' experiences of respite services for people with dementia and
      their perspectives on respite service development: a qualitative systematic
      review.
AB  - BACKGROUND: Respite services provide a break in the caregiving relationship for
      people with dementia and their carers, however they are often under-used and
      service acceptability can be low. This study aims to understand key stakeholders'
      experiences of respite services for people with dementia, with a view to
      informing respite service development. METHODS: A systematic search was conducted
      of the Pubmed/MedLine, Embase, Cinahl, PsychInfo, Scopus, Web of Science, and
      Cochrane databases (1980-2016, English) with fixed search terms relating to
      'respite' and 'dementia', following PRISMA guidelines. Noblit and Hare's approach
      to meta-ethnography was employed. Key concepts were identified across the papers
      and reciprocal and refutational translation techniques were applied to primary
      studies; findings were synthesized into third order interpretations and finally,
      a 'line-of-argument' was developed. RESULTS: In total 23 papers were reviewed,
      which described 20 independent samples across 12 countries. The views of 889
      participants were synthesized (13 people with dementia, 690 carers, 44 'service
      providers', 52 frontline staff, 70 managers, 12 volunteers, six academic/policy
      makers, and two independent consultants). Five key concepts were identified and
      outlined i.e. 1) the transition to service use 2) expanding organizational
      capacity 3) dementia care quality 4) building a collaborative care partnership
      and 5) dyad restoration. There was broad agreement around the key areas for
      service development across the range of stakeholders (flexible and responsive
      person-centred care, meaningful activity for people with dementia, enhanced
      client-service communication and informational support). However, there was clear
      divergence in stakeholder perspectives around the barriers to implementation of
      such developments. Organizational tension was evident between frontline staff and
      management in respite services, hindering the cultural change necessary to
      facilitate service development in line with dyad's needs and preferences.
      CONCLUSION: Respite services must surmount internal organizational barriers to
      change, and cultivate a collaborative solution-focused care culture, which
      acknowledges the centrality of the dyad and their care preferences. Future
      research should explore the development of alternative/modified community respite
      service models, which have greater capacity to be responsive to the needs of each
      individual dyad. The perspectives of people with dementia must be included in
      research in this area going forward. TRIAL REGISTRATION: PROSPERO Registration
      Number: CRD42016050191 .

PMID- 29216837
TI  - The role of gender in the active attitude toward treatment and health among older
      patients in primary health care-self-assessed health status and sociodemographic
      factors as moderators.
AB  - BACKGROUND: Active attitude toward treatment and health (ATH) leads to improved
      cooperation and better health outcomes in patients. Supporting it in the
      population of older adults is a growing need in primary care. Recognising the
      role of gender, health and other sociodemographic factors can help to distinguish
      patients who need the most assistance in activation from general practitioners
      (GPs). The objective of the study was to investigate gender differences in ATH as
      well as the moderating role of self-assessed health (SAH) and selected
      sociodemographic factors (age, education, financial status, marital status).
      METHODS: A cross-sectional, multicentre study among 4936 primary care older
      patients (aged 50+) was conducted. The PRACTA-Attitude toward Treatment and
      Health questionnaire (PRACTA-ATH) was used to measure the cognitive, emotional
      (positive and negative affect), and motivational dimensions of ATH. Patients were
      approached before and after their visits in the primary health-care facilities
      randomly selected in Central Poland. RESULTS: Generalised linear models (GENLIN)
      revealed the main effects of gender, SAH, and sociodemographic characteristics,
      such as financial status, marital status and education. Interaction effects of
      gender and age (Wald's chi2 = 24.767, p < 0.001 for ATH Global), as well as
      gender and SAH (Wald's chi2 = 16.712, p < 0.002 for ATH Global) on ATH were
      found. The most assistance in regard to ATH was required by men aged 50-74 and
      men declaring good self-assessed health. Generally, women declared a more active
      attitude than men, showing more knowledge (M = 5.40, SD = 0.07 and M = 5.21, SD =
      0.07, for women and men, respectively, p = 0.046), positive emotion (M = 5.55, SD
      = 0.06 and M = 5.33, SD =0.06, for women and men, respectively, p = 0.015) and
      motivation to be involved in their health issues (M = 5.71, SD = 0.07 and M =
      5.39, SD = 0.07, for women and men, respectively, p = 0.001). The level of
      negative emotions related to health was not significantly different between
      genders (p = 0.971). CONCLUSIONS: The need to create health promoting programmes
      taking account of particular gender differences in older adults emerges. In
      regard to clinical practice, building a sense of efficacy and individual
      responsibility for health, providing information about the means of health
      promotion and prevention, and recognising health-related cognitions, is
      recommended especially for men who feel well and are less advanced in age (50
      74).

PMID- 29216838
TI  - A prediction model to identify hospitalised, older adults with reduced physical
      performance.
AB  - BACKGROUND: Identifying older adults with reduced physical performance at the
      time of hospital admission can significantly affect patient management and
      trajectory. For example, such patients could receive targeted hospital
      interventions such as routine mobilisation. Furthermore, at the time of
      discharge, health systems could offer these patients additional therapy to
      maintain or improve health and prevent institutionalisation or readmission. The
      principle aim of this study was to identify predictors for persisting, reduced
      physical performance in older adults following acute hospitalisation. METHODS:
      This was a prospective cohort study that enrolled 117 medical patients, ages 65
      or older, who were admitted to a short-stay unit in a Danish emergency
      department. Patients were included in the study if at the time of admission they
      performed <=8 repetitions in the 30-s Chair-Stand Test (30s-CST). The primary
      outcome measure was the number of 30s-CST repetitions (<= 8 or >8) performed at
      the time of follow-up, 34 days after admission. Potential predictors within the
      first 48 h of admission included: age, gender, ability to climb stairs and walk
      400 m, difficulties with activities of daily living before admission, falls,
      physical activity level, self-rated health, use of a walking aid before
      admission, number of prescribed medications, 30s-CST, and the De Morton Mobility
      Index. RESULTS: A total of 78 (67%) patients improved in physical performance in
      the interval between admission and follow-up assessment, but 76 patients (65%)
      had persistent reduced physical performance when compared to their baseline (30s
      CST <= 8). The number of potential predictors was reduced in order to create a
      simplified prediction model based on 4 variables, namely the use of a walking aid
      before hospitalisation (score = 1.5), a 30s-CST <= 5 (1.8), age > 85 (0.1), and
      female gender (0.6). A score > 1.8 identified 78% of the older adults who
      continued to have reduced physical performance following acute hospitalisation.
      CONCLUSION: At the time of admission, the variables of age, gender, walking aid
      use, and a 30s-CST score <= 5 enabled clinicians to identify 78% of older adults
      who had persisting reduced physical performance following acute hospitalisation.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02474277 . (12.10.2014).

PMID- 29216839
TI  - Rates of morphological evolution, asymmetry and morphological integration of
      shell shape in scallops.
AB  - BACKGROUND: Rates of morphological evolution vary across different taxonomic
      groups, and this has been proposed as one of the main drivers for the great
      diversity of organisms on Earth. Of the extrinsic factors pertaining to this
      variation, ecological hypotheses feature prominently in observed differences in
      phenotypic evolutionary rates across lineages. But complex organisms are
      inherently modular, comprising distinct body parts that can be differentially
      affected by external selective pressures. Thus, the evolution of trait
      covariation and integration in modular systems may also play a prominent role in
      shaping patterns of phenotypic diversity. Here we investigate the role ecological
      diversity plays in morphological integration, and the tempo of shell shape
      evolution and of directional asymmetry in bivalved scallops. RESULTS: Overall,
      the shape of both valves and the magnitude of asymmetry of the whole shell
      (difference in shape between valves) are traits that are evolving fast in
      ecomorphs under strong selective pressures (gliders, recessers and nestling),
      compared to low rates observed in other ecomorphs (byssal-attaching, free-living
      and cementing). Given that different parts of an organism can be under different
      selective pressures from the environment, we also examined the degree of
      evolutionary integration between the valves as it relates to ecological shifts.
      We find that evolutionary morphological integration is consistent and
      surprisingly high across species, indicating that while the left and right valves
      of a scallop shell are diversifying in accordance with ecomorphology, they are
      doing so in a concerted fashion. CONCLUSIONS: Our study on scallops adds another
      strong piece of evidence that ecological shifts play an important role in the
      tempo and mode of morphological evolution. Strong selective pressures from the
      environment, inferred from the repeated evolution of distinct ecomorphs, have
      influenced the rate of morphological evolution in valve shape and the magnitude
      of asymmetry between valves. Our observation that morphological integration of
      the valves making up the shell is consistently strong suggests tight
      developmental pathways are responsible for the concerted evolution of these
      structures while environmental pressures are driving whole shell shape. Finally,
      our study shows that directional asymmetry in shell shape among species is an
      important aspect of scallop macroevolution.

PMID- 29216840
TI  - Over-The-Scope-Clip pre-mounted onto a double balloon enteroscope for fast and
      successful closure of post-EMR jejunal perforation: case report.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is a rare, autosomal dominant
      disease clinically characterized by the early onset of many adenomatous polyps
      throughout the colon, which turn into colon cancer, if left untreated. In FAP
      patients, polyps can also occur in the upper gastrointestinal (GI) tract,
      especially in the duodenum. Adenomas beyond duodenum are rare and mostly located
      in the proximal jejunum and distal ileum. The management of such polyps can be
      either surgical or endoscopic, depending on the features of the polyp, Spigelman
      stage and patient's clinical conditions. Endoscopic mucosal resection (EMR) of
      jejunal polyps can be challenging, because of the thinner wall of jejunum,
      compared to the rest of the GI tract, and of the difficulty of maintaining
      control and stability of the scope. For these reasons, jejunal perforation is a
      likely occurrence. CASE PRESENTATION: A 65-year-old woman with a stage IV FAP,
      who had previously undergone abdominal surgery because of her disease, came to
      our attention because of numerous adenomatous-looking duodenal polyps and a 25 mm
      lesion in proximal jejunum. According to Spigelman staging system, patient was
      candidate for surgical resection, in light of the risk of developing small bowel
      cancer. Despite the benefits of surgery were clearly explained to her, she
      refused to undergo small bowel resection. Therefore, EMR of the largest duodenal
      polyp and of the jejunal lesion was planned. After the removal of the jejunal
      polyp, a small perforation was noted. We were able to rapidly close such
      perforation by using the Over-The-Scope-Clip system (OTSC, 12/6 t; Ovesco,
      Tubingen, Germany) pre-mounted onto a double balloon (DB) enteroscope.
      CONCLUSIONS: The endoscopic management of jejunal perforation can be tricky and
      the placement of traditional through-the-scope clips in a narrow space like
      jejunum may be difficult and time consuming. This case describes the use of the
      OTSC system pre-mounted onto a DB enteroscope for the closure of post-EMR jejunal
      perforation.

PMID- 29216841
TI  - Medical overuse and quaternary prevention in primary care - A qualitative study
      with general practitioners.
AB  - BACKGROUND: Medical overuse is a topic of growing interest in health care systems
      and especially in primary care. It comprises both over investigation and
      overtreatment. Quaternary prevention strategies aim at protecting patients from
      unnecessary or harmful medicine. The objective of this study was to gain a deeper
      understanding of relevant aspects of medical overuse in primary care from the
      perspective of German general practitioners (GPs). We focused on the scope,
      consequences and drivers of medical overuse and strategies to reduce it
      (=quaternary prevention). METHODS: We used the qualitative Grounded Theory
      approach. Theoretical sampling was carried out to recruit GPs in Bavaria,
      Germany. We accessed the field of research through GPs with academic affiliation,
      recommendations by interview partners and personal contacts. They differed in
      terms of primary care experience, gender, region, work experience abroad,
      academic affiliation, type of specialist training, practice organisation and
      position. Qualitative in-depth face-to-face interviews with a semi-structured
      interview guide were conducted (n = 13). The interviews were audiotaped and
      transcribed verbatim. Data analysis was carried out using open and axial coding.
      RESULTS: GPs defined medical overuse as unnecessary investigations and treatment
      that lack patient benefit or bear the potential to cause harm. They observed that
      medical overuse takes place in all three German reimbursement categories:
      statutory health insurance, private insurance and individual health services
      (direct payment). GPs criticised the poor acceptance of gate-keeping in German
      primary care. They referred to a low-threshold referral policy and direct patient
      access to outpatient secondary care, leading to specialist treatment without
      clear medical indication. The GPs described various direct drivers of medical
      overuse within their direct area of influence. They also emphasised indirect
      drivers related to system or societal processes. The proposed strategies for
      reducing medical overuse included a well-founded wait-and-see approach, medical
      education, a trustful doctor-patient relationship, the improvement of
      primary/health care structures and the involvement of patients and society.
      CONCLUSIONS: GPs are frequently located at the starting point of the diagnostic
      and treatment process. They have the potential to play a vital role in quaternary
      prevention. This requires a debate going beyond the medical profession and
      involving society as a whole.

PMID- 29216842
TI  - A clinical tool to predict Plasmodium vivax recurrence in Malaysia.
AB  - BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various
      geographic regions. Interestingly, South-East Asia and the Asia-Pacific region
      are documented to exhibit the most frequent recurrence incidences. Identifying
      patients at a higher risk for recurrences gives valuable information in
      strengthening the efforts to control P. vivax infections. The aim of the study
      was to develop a tool to identify P. vivax- infected patients that are at a
      higher risk of recurrence in Malaysia. METHODS: Patient data was obtained
      retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016.
      Patients with incomplete data were excluded. A total of 2044 clinical P. vivax
      malaria cases treated with primaquine were included. Data collected were patient,
      disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were
      used to develop a clinical risk score, while the remaining third (n = 682) was
      used for validation. RESULTS: Using multivariate analysis, age (p = 0.03),
      gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of
      treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found
      to be predictors of recurrence after controlling for other confounding factors;
      these predictors were then used in developing the final model. The beta
      coefficient values were used to develop a clinical scoring tool to predict
      possible recurrence. The total scores ranged between 0 and 8. A higher score
      indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence
      interval [CI]: 1.562-2.487; p <= 0.001). The area under the receiver operating
      characteristic (ROC) curve of the developed (n = 1362) and validated model (n =
      682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value < 0.001, and
      ROC: 0.766, 95% CI: 0.700-0.833, p-value < 0.001, respectively). In both the
      developed and validated models, area under the ROC curves showed no significant
      difference in predicting recurrence based on the constructed scoring mechanism (p
      = 0.399; Z-value: -0.8441; standard error: 0.045). CONCLUSIONS: The developed
      model to predict recurrence was found to be of good accuracy and could be a
      useful tool in targeting patients at a higher risk for recurrence for closer
      monitoring during follow-up, after treatment with primaquine.

PMID- 29216843
TI  - Evaluation of the visibility of early gastric cancer using linked color imaging
      and blue laser imaging.
AB  - BACKGROUND: Blue laser imaging (BLI) and linked color imaging (LCI) are the color
      enhancement features of the LASEREO endoscopic system, which provide a narrow
      band light observation function and expansion and reduction of the color
      information, respectively. METHODS: We examined 82 patients with early gastric
      cancer (EGC) diagnosed between April 2014 and August 2015. Five expert and 5 non
      expert endoscopists retrospectively compared images obtained on non-magnifying
      BLI bright mode (BLI-BRT) and LCI with those obtained via conventional white
      light imaging (WLI). Interobserver agreement was also assessed. RESULTS: In
      experts' evaluation of the images, an improvement in visibility was observed in
      73% (60/82) and 20% (16/82) of cases under LCI and BLI-BRT, respectively. In non
      experts' evaluation of the images, an improvement in visibility was observed in
      76.8% (63/82) and 24.3% (20/82) of cases under LCI and BLI-BRT, respectively.
      There were no significant differences between experts and non-experts in the
      evaluation of the images. The improvement in visibility was significantly higher
      with LCI than with BLI-BRT in experts and non-experts (p < 0.01). With regard to
      tumor color on WLI, the improvement in the visibility of reddish and whitish
      tumors was significantly higher than that of isochromatic tumors when LCI was
      used. The improvement in visibility with LCI was observed in 71% (12/17) and 74%
      (48/65) of patients with and without Helicobacter pylori (Hp) eradication,
      respectively; no significant difference in improvement was observed between these
      groups. The interobserver agreement was good to satisfactory at >= 0.62.
      CONCLUSIONS: In conclusion, our study showed that LCI improved the visibility of
      EGC, regardless of the level of endoscopists' experience or Hp eradication in
      patients, particularly for EGCs with a reddish or whitish color. The improvement
      in visibility was significantly higher with LCI than that with BLI.

PMID- 29216844
TI  - Comparative analyses of plastid genomes from fourteen Cornales species:
      inferences for phylogenetic relationships and genome evolution.
AB  - BACKGROUND: The Cornales is the basal lineage of the asterids, the largest
      angiosperm clade. Phylogenetic relationships within the order were previously not
      fully resolved. Fifteen plastid genomes representing 14 species, ten genera and
      seven families of Cornales were newly sequenced for comparative analyses of
      genome features, evolution, and phylogenomics based on different partitioning
      schemes and filtering strategies. RESULTS: All plastomes of the 14 Cornales
      species had the typical quadripartite structure with a genome size ranging from
      156,567 bp to 158,715 bp, which included two inverted repeats (25,859-26,451 bp)
      separated by a large single-copy region (86,089-87,835 bp) and a small single
      copy region (18,250-18,856 bp) region. These plastomes encoded the same set of
      114 unique genes including 31 transfer RNA, 4 ribosomal RNA and 79 coding genes,
      with an identical gene order across all examined Cornales species. Two genes
      (rpl22 and ycf15) contained premature stop codons in seven and five species
      respectively. The phylogenetic relationships among all sampled species were fully
      resolved with maximum support. Different filtering strategies (none, light and
      strict) of sequence alignment did not have an effect on these relationships. The
      topology recovered from coding and noncoding data sets was the same as for the
      whole plastome, regardless of filtering strategy. Moreover, mutational hotspots
      and highly informative regions were identified. CONCLUSIONS: Phylogenetic
      relationships among families and intergeneric relationships within family of
      Cornales were well resolved. Different filtering strategies and partitioning
      schemes do not influence the relationships. Plastid genomes have great potential
      to resolve deep phylogenetic relationships of plants.

PMID- 29216845
TI  - A comparison of the test-negative and the traditional case-control study designs
      for estimation of influenza vaccine effectiveness under nonrandom vaccination.
AB  - BACKGROUND: As annual influenza vaccination is recommended for all U.S. persons
      aged 6 months or older, it is unethical to conduct randomized clinical trials to
      estimate influenza vaccine effectiveness (VE). Observational studies are being
      increasingly used to estimate VE. We developed a probability model for comparing
      the bias and the precision of VE estimates from two case-control designs: the
      traditional case-control (TCC) design and the test-negative (TN) design. In both
      study designs, acute respiratory illness (ARI) patients seeking medical care
      testing positive for influenza infection are considered cases. In the TN design,
      ARI patients seeking medical care who test negative serve as controls, while in
      the TCC design, controls are randomly selected individuals from the community who
      did not contract an ARI. METHODS: Our model assigns each study participant a
      covariate corresponding to the person's health status. The probabilities of
      vaccination and of contracting influenza and non-influenza ARI depend on health
      status. Hence, our model allows non-random vaccination and confounding. In
      addition, the probability of seeking care for ARI may depend on vaccination and
      health status. We consider two outcomes of interest: symptomatic influenza (SI)
      and medically-attended influenza (MAI). RESULTS: If vaccination does not affect
      the probability of non-influenza ARI, then VE estimates from TN studies usually
      have smaller bias than estimates from TCC studies. We also found that if
      vaccinated influenza ARI patients are less likely to seek medical care than
      unvaccinated patients because the vaccine reduces symptoms' severity, then
      estimates of VE from both types of studies may be severely biased when the
      outcome of interest is SI. The bias is not present when the outcome of interest
      is MAI. CONCLUSIONS: The TN design produces valid estimates of VE if (a)
      vaccination does not affect the probabilities of non-influenza ARI and of seeking
      care against influenza ARI, and (b) the confounding effects resulting from non
      random vaccination are similar for influenza and non-influenza ARI. Since the
      bias of VE estimates depends on the outcome against which the vaccine is supposed
      to protect, it is important to specify the outcome of interest when evaluating
      the bias.

PMID- 29216846
TI  - Reduced level of arousal and increased mortality in adult acute medical
      admissions: a systematic review and meta-analysis.
AB  - BACKGROUND: Reduced level of arousal is commonly observed in medical admissions
      and may predict in-hospital mortality. Delirium and reduced level of arousal are
      closely related. We systematically reviewed and conducted a meta-analysis of
      studies in adult acute medical patients of the relationship between reduced level
      of arousal on admission and in-hospital mortality. METHODS: We conducted a
      systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We
      included studies of adult patients admitted with acute medical illness with level
      of arousal assessed on admission and mortality rates reported. We performed meta
      analysis using a random effects model. RESULTS: From 23,941 studies we included
      21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years.
      Studies considered unselected general medical admissions (8 studies, n=13,039) or
      specific medical conditions (13 studies, n=38,882). Methods of evaluating level
      of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9%
      (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of
      arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI
      4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and
      possible publication bias). CONCLUSIONS: Reduced level of arousal on hospital
      admission may be a strong predictor of in-hospital mortality. Most evidence was
      of low quality. Reduced level of arousal is highly specific to delirium, better
      formal detection of hypoactive delirium and implementation of care pathways may
      improve outcomes. Future studies to assess the impact of interventions on in
      hospital mortality should use validated assessments of both level of arousal and
      delirium.

PMID- 29216847
TI  - Magnetic resonance imaging analysis of brain function in patients with irritable
      bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional disease of the
      gastrointestinal tract. The current study aimed to examine the association
      between visceral hypersensitivity in IBS and cortical activation using functional
      magnetic resonance imaging (fMRI), and to elucidate the role of psychological
      factors in the pathogenesis of IBS. METHODS: The present study included 31
      patients with IBS and 20 healthy controls. Cerebral function was assessed using
      fMRI. During imaging, a Sengstaken-Blakemore tube was placed within the rectum
      approximately 10 cm from the anus, following which gas was rapidly injected into
      the airbag using a 150-ml syringe. Images were obtained at 40 ml, 80 ml, and 120
      ml of expansion. Psychological status was evaluated using the Hospital Anxiety
      and Depression Scale (HADS). RESULTS: Anxiety and depression scores were higher
      among patients with IBSthan among controls (both P < 0.05), although scores in
      both groups were below the level of clinical diagnosis. Brain activation in
      regions of interest (parietal areas, prefrontal cortex, cerebellum, anterior
      cingulate cortex, insular cortex, and thalamus) increased along with increases in
      rectal balloon dilation, except in women with IBS and patients with disease
      duration less than 5 years. Furthermore, region of interest (ROI) activation
      (such as the parietal region, prefrontal cortex, cerebellum, anterior cingulate
      cortex, insular cortex, and thalamus) differed significantly between the 40-ml
      and 120-ml conditions, and between the 80-ml and 120-ml conditions (P < 0.05),
      among patients with IBS with anxiety or depression scores less than 9 points.
      CONCLUSIONS: Overall, our findings indicate that changes in brain activation due
      to changes in rectal balloon distension can be objectively and accurately
      measured using fMRI. Although our results indicated that visceral
      hypersensitivity during IBS is associated with changes in cortical activation,
      further studies utilizing larger sample sizes are required to more fully
      elucidate the association between psychological factors and visceral
      hypersensitivity in IBS.

PMID- 29216848
TI  - Anterior sacral meningocele infected with Fusobacterium in a patient with
      recently diagnosed colorectal carcinoma - a case report.
AB  - BACKGROUND: Anterior sacral meningoceles are rare, and usually occur with other
      malformations of the posterior lower spine. While these are more frequently
      reported in pediatric cohorts, we report a case in an elderly woman. CASE
      PRESENTATION: We report on a 71 year-old woman with a recently diagnosed
      colorectal adenocarcinoma who presented with a severe bacterial meningitis. The
      cerebrospinal fluid cell count revealed a pleocytosis of 80,000 cells/MUl and a
      severe disturbance of the blood-brain-barrier. Fusobacterium nucleatum was
      cultured as the causing pathogen. A lumbar MRI showed, in addition to contrast
      enhancing meninges as sign of inflammation, a presacral mass. In the next step,
      the mass was diagnosed as an anterior sacral meningocele connected to the gut. An
      adequate antibiotic was used to treat the leptomeningitis. The connection between
      gut and meningocele was closed surgically and the patient recovered well and
      underwent further treatment of her colorectal adenocarcinoma. CONCLUSION: We
      report on a case of meningitis with an anterior sacral meningocele that was
      connected to the gut in a patient with a infiltrative colorectal adenocarcinoma.
      Anatomic variants have to be considered as rare causes of meningitis with typical
      intestinal germs.

PMID- 29216849
TI  - Economic evaluations of ergonomic interventions preventing work-related
      musculoskeletal disorders: a systematic review of organizational-level
      interventions.
AB  - BACKGROUND: Work-related musculoskeletal disorders (WMSD) represent a major
      public health problem and economic burden to employers, workers and health
      insurance systems. This systematic review had two objectives: (1) to analyze the
      cost-benefit results of organizational-level ergonomic workplace-based
      interventions aimed at preventing WMSD, (2) to explore factors related to the
      implementation process of these interventions (obstacles and facilitating
      factors) in order to identify whether economic results may be due to a successful
      or unsuccessful implementation. METHODS: Systematic review. Studies were searched
      in eight electronic databases and in reference lists of included studies.
      Companion papers were identified through backward and forward citation tracking.
      A quality assessment tool was developed following guidelines available in the
      literature. An integration of quantitative economic results and qualitative
      implementation data was conducted following an explanatory sequential design.
      RESULTS: Out of 189 records, nine studies met selection criteria and were
      included in our review. Out of nine included studies, grouped into four types of
      interventions, seven yielded positive economic results, one produced a negative
      result and one mixed results (negative cost-effectiveness and positive net
      benefit). However, the level of evidence was limited for the four types of
      interventions given the quality and the limited number of studies identified. Our
      review shows that among the nine included studies, negative and mixed economic
      results were observed when the dose delivered and received by participants was
      low, when the support from top and/or middle management was limited either due to
      limited participation of supervisors in training sessions or a lack of financial
      resources and when adequacy of intervention to workers' needs was low. In studies
      where economic results were positive, implementation data showed strong support
      from supervisors and a high rate of employee participation. CONCLUSION: Studies
      investigating the determinants of financial outcomes of prevention related to
      implementation process are very seldom. We recommend that in future research
      economic evaluation should include information on the implementation process in
      order to permit the interpretation of economic results and enhance the
      generalizability of results. This is also necessary for knowledge transfer and
      utilization of research results for prevention-oriented decision-making in
      occupational health and safety.

PMID- 29216850
TI  - Adolescent substance use behavior and suicidal behavior for boys and girls: a
      cross-sectional study by latent analysis approach.
AB  - BACKGROUND: Adolescent suicidal behavior may consist of different symptoms,
      including suicidal ideation, suicidal planning and suicidal attempts. Adolescent
      substance use behavior may contribute to adolescent suicidal behavior. However,
      research on the relationships between specific substance use and individual
      suicidal behavior is insufficient, as adolescents may not use only one substance
      or develop only one facet of suicidal behavior. Latent variables permit us to
      describe the relationships between clusters of related behaviors more accurately
      than studying the relationships between specific behaviors. Thus, the aim of this
      study was to explore how adolescent substance use behavior contributes to
      suicidal behavior using latent variables representing adolescent suicidal and
      substance use behaviors. METHOD: A total of 13,985 adolescents were recruited
      using a stratified random sampling strategy. The participants indicated whether
      they had experienced suicidal ideation, planning and attempts and reported their
      cigarette, alcohol, ketamine and MDMA use during the past year. Latent analysis
      was used to examine the relationship between substance use and suicidal behavior.
      RESULTS: Adolescents who used any one of the above substances exhibited more
      suicidal behavior. The results of latent variables analysis revealed that
      adolescent substance use contributed to suicidal behavior and that boys exhibited
      more severe substance use behavior than girls. However, there was no gender
      difference in the association between substance use and suicidal behavior.
      CONCLUSION: Substance use behavior in adolescents is related to more suicidal
      behavior. In addition, the contribution of substance use to suicidal behavior
      does not differ between genders.

PMID- 29216851
TI  - What does IGRA testing add to the diagnosis of ocular tuberculosis? A Bayesian
      latent class analysis.
AB  - BACKGROUND: To evaluate the contribution made to the diagnostic work-up for
      patients with suspected ocular tuberculosis (TB) by QuantiFERON-TB Gold In-Tube
      (QFT) tests using latent class analysis model. METHODS: A single centre
      retrospective cohort study. A Bayesian latent class model was constructed on the
      basis of demographics, phenotypes and test results from patients attending a
      tertiary referral center in the UK. This estimated the probability of ocular TB
      for each patient in two versions, first with and then without QFT. The estimated
      probability of ocular TB was compared with treatment failure. RESULTS: From a
      database of 365 patients with clinical signs suggestive of ocular TB, 267
      patients who had QFT and complete data were evaluated. Mean age was 45.0 +/- 15.4
      years with 141 (52.9%) male and 148 (50.5%) of Asian ethnicity. QFT was positive
      in 208 (70.1%) patients and ATT was instituted in 145 (49.5%) patients with 100
      (34.1%) patients also having concurrent systemic corticosteroid therapy. The best
      estimate of a QFT level separating TB-positive and TB-negative patients was
      extremely low. This weak discrimination between TB and non-TB groups was
      reflected in poor positive and negative predictive values for treatment failure.
      CONCLUSIONS: The latent class model did not successfully predict treatment
      failure, despite taking all variables into account. The threshold between TB and
      non-TB in QFT values was implausibly low and removing QFT from the model made
      prediction slightly worse. A larger prospective study is required to establish
      the role of all tests, demographics and phenotypes in diagnosis.

PMID- 29216852
TI  - Access to affordable medicines and diagnostic tests for asthma and COPD in sub
      Saharan Africa: the Ugandan perspective.
AB  - BACKGROUND: Equitable access to affordable medicines and diagnostic tests is an
      integral component of optimal clinical care of patients with asthma and chronic
      obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about
      the availability, cost and affordability of medicines and diagnostic tests
      essential in asthma and COPD management. METHODS: Data on the availability, cost
      and affordability of 17 medicines and 2 diagnostic tests essential in asthma and
      COPD management were collected from 22 public hospitals, 23 private and 85
      private pharmacies. The percentage of the available medicines and diagnostic
      tests, the median retail price of the lowest priced generic brand and
      affordability in terms of the number of days' wages it would cost the least paid
      public servant were analysed. RESULTS: The availability of inhaled short acting
      beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA
      ICS combinations and inhaled corticosteroids (ICS) in all the study sites was
      75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled
      long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist
      (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were
      available in 24.4% and 6.7% of the study sites respectively. Affordability ranged
      from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for
      formoterol/budesonide inhalers and 27.8 days' wages for spirometry. CONCLUSION:
      Medicines and diagnostic tests essential in asthma and COPD care are not widely
      available in Uganda and remain largely unaffordable. Strategies to improve access
      to affordable asthma and COPD medicines and diagnostic tests should be
      implemented in Uganda.

PMID- 29216853
TI  - Obesity associates with vasomotor symptoms in postmenopause but with physical
      symptoms in perimenopause: a cross-sectional study.
AB  - BACKGROUND: Middle-aged women experience various menopausal symptoms during the
      menopause. These symptoms can affect their quality of life and health. Several
      epidemiological studies reported that obesity associates with menopausal
      symptoms. The aim of this cross-sectional study was to examine the associations
      between obesity and multiple menopausal symptoms at different stages of menopause
      in middle-aged Korean women. METHODS: The study population included women aged 44
      56 years who visited a tertiary referral hospital for medical check-ups between
      November 2012 and March 2013 and were free from serious illness, could comprehend
      a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire
      was used to assess the prevalence of menopausal symptoms. Overweight and obesity
      were defined as body mass index (BMI) of 23-24.9 and >=25 kg/m2, respectively.
      RESULTS: Of the 2204 middle-aged women, 929 met the eligibility criteria. Of
      these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause,
      respectively. In perimenopause, obese women were significantly more likely to
      have moderate/severe physical symptoms (MENQOL domain score >= 5) than normal or
      overweight women. In postmenopause, obese women were significantly more likely to
      have moderate/severe vasomotor symptoms. Multiple linear regression with
      adjustment for confounders showed that relative to normal weight, obesity in
      perimenopause and postmenopause associated independently with physical symptoms
      (beta coefficient = 0.35; P = 0.023) and vasomotor symptoms (beta coefficient =
      0.68; P = 0.003), respectively. Overweight did not associate with menopausal
      symptoms. BMI did not associate significantly with psychosocial or sexual
      symptoms at either stage of menopause. CONCLUSIONS: Obese women had more frequent
      menopausal symptoms than normal or overweight women but the associated menopausal
      symptom differed depending on the menopausal stage. Further studies are required
      to confirm this result and identify the underlying mechanisms.

PMID- 29216854
TI  - Acute clouding of trifocal lens during implantation: a case report.
AB  - BACKGROUND: Intraoperative IOLs clouding of several kinds of hydrophilic acrylic
      intraocular lenses (IOLs) have been reported due to temperature changes. This
      phenomenon reported previously occurred in cold countries and during the winter
      months. However, no clinical case was reported about trifocal IOL opacification
      during operation. We report a case in which acute opacification of the optical
      region occurred simultaneously when AT LISA tri 839mp(Carl Zeiss) was implanted
      into the eye. CASE PRESENTATION: A 79-year-old woman with a cortex and nucleus
      cataract was scheduled to undergo right eye phacoemulsification assisted by
      femtosecond technique. The trifocal lens (AT LISA tri 839mp), which is made of
      hydrophilic acrylic (25%) with hydrophobic surface properties, was chosen for
      implantation. As the IOL was implanted into the eye, it became cloudy
      immediately. Then it was replaced by another AT LISA tri 839mp, which was
      transferred from lens company outside, the same phenomenon was observed. These
      two lenses underwent the same temperature fluctuation from cold outside to
      operating room. Finally, a ZCB00 (Allergan) was implanted. CONCLUSIONS: The acute
      intraoperative clouding of trifocal lens(AT LISA tri 839mp) results from
      fluctuation of temperature should be noticed.

PMID- 29216855
TI  - Impact of rapid investigation clinic on timeliness of lung cancer diagnosis and
      treatment.
AB  - BACKGROUND: Guidelines recommend timely evaluation of patients with suspected
      lung cancer. We evaluated the impact of a Rapid Investigation Clinic (RIC) on
      timeliness of lung cancer diagnosis and treatment between February 2010 and
      December 2011. METHODS: Investigation within the RIC was conducted by a
      pulmonologist and a nurse clinician. Controls were patients with lung cancer,
      investigated outside the RIC at the same institution during the same time period.
      The primary outcome was time between first contact with a local physician for
      suspected lung cancer (T0) and first treatment. Factors associated with the delay
      from T0 to first treatment were examined using multivariate analysis.
      Completeness of lung cancer staging according to guidelines was assessed.
      RESULTS: A total of 195 patients were investigated within the RIC vs. 132
      patients outside the RIC. The median delay between T0 and first treatment was 65
      days (interquartile range [IQR] 46-92 days) in the RIC and 78 days (IQR 49-119
      days) in the non-RIC patients (p <= 0.01). Time from T0 to pathological diagnosis
      was shorter in the RIC (median 26 days; IQR 14-42 days) vs. non-RIC patients
      (median 40 days; IQR 16-68 days). In multivariate analysis, investigation in the
      RIC was associated with a reduction in time to first treatment of 24 days (95%
      confidence interval [CI] 12-35 days) when adjusted for relevant confounders.
      Guideline-concordant investigation occurred more frequently in RIC patients,
      based on the quality indicators examined. CONCLUSIONS: A Rapid Investigation
      Clinic reduces delays to lung cancer diagnosis and treatment, and impacts quality
      of care.

PMID- 29216856
TI  - Interactional justice at work is related to sickness absence: a study using
      repeated measures in the Swedish working population.
AB  - BACKGROUND: Research has shown that perceived unfairness contributes to higher
      rates of sickness absence. While shorter, but more frequent periods of sickness
      absence might be a possibility for the individual to get relief from high strain,
      long-term sickness absence might be a sign of more serious health problems. The
      Uncertainty Management Model suggests that justice is particularly important in
      times of uncertainty, e.g. perceived job insecurity. The present study
      investigated the association between interpersonal and informational justice at
      work with long and frequent sickness absence respectively, under conditions of
      job insecurity. METHODS: Data were derived from the 2010, 2012, and 2014 biennial
      waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH). The
      final analytic sample consisted of 19,493 individuals. We applied repeated
      measures regression analyses through generalized estimating equations (GEE), a
      method for longitudinal data that simultaneously analyses variables at different
      time points. We calculated risk of long and frequent sickness absence,
      respectively in relation to interpersonal and informational justice taking
      perceptions of job insecurity into account. RESULTS: We found informational and
      interpersonal justice to be associated with risk of long and frequent sickness
      absence independently of job insecurity and demographic variables. Results from
      autoregressive GEE provided some support for a causal relationship between
      justice perceptions and sickness absence. Contrary to expectations, we found no
      interaction between justice and job insecurity. CONCLUSIONS: Our results
      underline the need for fair and just treatment of employees irrespective of
      perceived job insecurity in order to keep the workforce healthy and to minimize
      lost work days due to sickness absence.

PMID- 29216857
TI  - Images of God and attitudes towards death in relation to spiritual wellbeing: an
      exploratory side study of the EORTC QLQ-SWB32 validation study in palliative
      cancer patients.
AB  - BACKGROUND: When patients are facing the ends of their lives, spiritual concerns
      often become more important. It is argued that effective, integrated palliative
      care should include addressing patients' spiritual wellbeing. In 2002 the EORTC
      Quality of Life Group began an international study to develop an spiritual
      wellbeing measure for palliative patients (SWB). Spiritual wellbeing is a complex
      construct, which comprises multiple contributory components. While conducting the
      EORTC SWB validation study with Dutch palliative cancer patients we also
      conducted an exploratory side study to examine the relationship between their
      spiritual wellbeing, images of God, and attitudes towards death. METHODS:
      Patients with incurable cancer who were able to understand Dutch and were well
      enough to participate, completed the provisional SWB measure and two scales
      assessing "Images of God" and "attitudes towards death and afterlife". Linear
      stepwise regression analysis was conducted to assess the relation between SWB and
      other factors. RESULTS: Fifty two Dutch patients, 28 females and 24 males,
      participated. The whole SWB measure validation identified four scoring scales:
      Existential (EX), Relationship with Self (RS), Relationships with Others (RO),
      Relationship with Something Greater (RSG) and Relationship with God (RG, for
      believers only). Adherence to an image of an Unknowable God and a worse WHO
      performance status were negatively associated with the EX scale. The image of an
      Unknowable God was also found to be negatively associated with the RS scale.
      Higher education correlated positively with the RO scale. Adherence to a Personal
      or Non-Personal Image of God was not found to be positively influencing any of
      the domains of SWB. CONCLUSIONS: For our participants, an Unknowable Image of God
      had a negative relationship with their SWB. Furthermore, specific images of God
      (Personal or Non Personal) are not associated with domains of SWB. Together,
      these findings suggest that spiritual wellbeing surpasses traditional religious
      views. The development of a new language which more naturally expresses different
      images of a higher being amongst patients in western late-modern societies may
      further aid our understanding and subsequently lead to an improvement in
      patients' spiritual wellbeing.

PMID- 29216858
TI  - Use of a hydrophilic coating wire reduces significantly the rate of central vein
      punctures and the incidence of pneumothorax in totally implantable access port
      (TIAP) surgery.
AB  - BACKGROUND: Insertion of a Totally Implantable Access Port (TIAP) can be
      performed either via Central VeinPuncture (CVP) or Brachiocephalic Vein Cut-down
      (venous section-VS). The primary success rate of TIAPimplantation using VS rarely
      ever achieves 100%. The objective of this study was to describe a modified
      VSapproach using a hydrophilic coated wire (TVS). METHODS: From 01.01.2015 to
      31.12.2015, all patients receiving TIAP implantations were screened. During this
      time,all patients in whom the primary VS procedure was found to be unsuccessful
      were analysed. RESULTS: In 2015, 1152 patients had TIAP implantations performed
      by 24 different surgeons. Of these, 277 patientsneeded a second line rescue
      strategy either by CVP (n = 69) or TVS (n = 208). There were no statistically
      significantdifferences regarding demographics or indication for TIAP implantation
      between CVP and TVS. The operation time andthe qualification of the operating
      surgeon between CVP and TVS did not differ significantly. After the introduction
      ofthe guidewire with a hydrophilic coated wire, the need for CVP decreased
      significantly from 12.7% to 8.8% (p < 0.0001).In patients receiving CVP as a
      second line rescue strategy, the incidence of pneumothorax (n = 3 patients
      (4.3%)) wassignificantly higher compared to patients with TVS as a second line
      rescue strategy (n = 1 patient (0.48%), p = 0.02). CONCLUSION: The use of a
      hydrophilic coated wire significantly decreased the number of CVP and the
      incidence ofpneumothorax. TVS is a safe and successful second-line rescue
      strategy.

PMID- 29216859
TI  - A simple prediction tool for inhaled corticosteroid response in asthmatic
      children.
AB  - BACKGROUND: Inhaled corticosteroids are recommended as the first-line controller
      medication for childhood asthma owing to their multiple clinical benefits.
      However, heterogeneity in the response towards these drugs remains a significant
      clinical problem. METHODS: Children aged 5 to 18 years with mild to moderate
      persistent asthma were recruited into the Taiwanese Consortium of Childhood
      Asthma Study. Their responses to inhaled corticosteroids were assessed based on
      their improvements in the asthma control test and peak expiratory flow. The
      predictors of responsiveness were demographic and clinical features that were
      available in primary care settings. We have developed a prediction model using
      logistic regression and have simplified it to formulate a practical tool. We
      assessed its predictive performance using the area under the receiver operating
      characteristic curve. RESULTS: Of the 73 asthmatic children with baseline and
      follow-up outcome measurements for inhaled corticosteroids treatment, 24 (33%)
      were defined as non-responders. The tool we have developed consisted of three
      predictors yielding a total score between 0 and 5, which are comprised of the
      following parameters: the age at physician-diagnosis of asthma, sex, and exhaled
      nitric oxide. Sensitivity and specificity of the tool for prediction of inhaled
      corticosteroids non-responsiveness, for a score of 3, were 0.75 and 0.69,
      respectively. The areas under the receiver operating characteristic curve for the
      prediction tool was 0.763. CONCLUSIONS: Our prediction tool represents a simple
      and low-cost method for predicting the response of inhaled corticosteroids
      treatment in asthmatic children.

PMID- 29216860
TI  - 'The End of Sitting' in a public space: observations of spontaneous visitors.
AB  - BACKGROUND: Sitting too much has been associated with negative health outcomes.
      'The End of Sitting' is a newly developed office landscape that moves away from
      the traditional chair-desk setup. The landscape aims to reduce sitting time by
      offering a variety of (supported) standing positions. The aim of this study was
      to determine the usage of the landscape after being placed in the main entrance
      hall of the VU University in Amsterdam. METHODS: We observed the number of
      spontaneous visitors as well as the duration of visits, changes to another
      location within the landscape, and adopted postures. Using questionnaires reasons
      (not) to visit the landscape, perceived affordances of the landscape and
      associations with long-term use were determined. RESULTS: Observed numbers of
      visitors were relatively low and duration of visits were short, which seemed to
      indicate visitors were trying out the landscape. The majority of visitors were in
      an upright position, reflecting the designers' intentions. Visitors indicated
      that long-term use would be pleasant to them. CONCLUSION: 'The End of Sitting'
      landscape received positive reactions but number of visits were limited in the
      few months that it was placed in the university main entrance hall. The landscape
      might be better suited for designated working or study spaces, for which it was
      originally intended. It might also be worth to explore the landscapes suitability
      for short stay environments, such as waiting rooms.

PMID- 29216861
TI  - Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in
      schizophrenia: an fMRI study.
AB  - BACKGROUND: Schizophrenia has a negative effect on the activity of the temporal
      and prefrontal cortices in the processing of emotional facial expressions.
      However no previous research focused on the evaluation of mixed emotions in
      schizophrenia, albeit they are frequently expressed in everyday situations and
      negative emotions are frequently expressed by mixed facial expressions. METHODS:
      Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control
      subjects were enrolled in the study. The two study groups did not differ in age
      and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%),
      10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions.
      During the fMRI acquisition pictures were presented in a randomized order and
      subjects had to categorize expressions by button press. RESULTS: A decreased
      activation was found in the patient group during fear, mixed fear and mixed happy
      processing in the right ventrolateral prefrontal cortex (VLPFC) and the right
      anterior insula (RAI) at voxel and cluster level after familywise error
      correction. No difference was found between study groups in activations to happy
      facial condition. Patients with schizophrenia did not show a differential
      activation between mixed happy and happy facial expression similar to controls in
      the right dorsolateral prefrontal cortex (DLPFC). CONCLUSIONS: Patients with
      schizophrenia showed decreased functioning in right prefrontal regions
      responsible for salience signaling and valence evaluation during emotion
      recognition. Our results indicate that fear and mixed happy/fear processing are
      impaired in schizophrenia, while happy facial expression processing is relatively
      intact.

PMID- 29216862
TI  - The incidence and risk factors of asymptomatic primary spontaneous pneumothorax
      detected during health check-ups.
AB  - BACKGROUND: Patients with primary spontaneous pneumothorax (PSP) usually complain
      of sudden-onset dyspnea and pleuritic chest pain. However, asymptomatic PSP has
      been incidentally detected on chest X-rays. In this study, we analyzed the
      incidence, characteristics, risk factors, and prognosis of asymptomatic PSP
      detected during regular medical check-ups in university students. METHODS: In
      this study, 101,709 chest X-rays were performed during medical check-ups for
      students at the University of Tokyo between April 2011 and March 2016. Among
      them, 43 cases of asymptomatic PSP (0.042%) were detected. We calculated the lung
      collapse rate of pneumothorax using Kircher's method. We also analyzed risk
      factors associated with asymptomatic PSP using characteristics inspected in
      medical check-ups. RESULTS: The incidence of asymptomatic PSP was significantly
      higher in men than in women (0.050% vs 0.018%). Multivariate analysis revealed an
      association of younger age, greater height, lower body mass index, and greater
      height growth per year with an increased risk of asymptomatic PSP in male
      students. Mild lung collapse (<10%) was present in 22 of 43 students with
      asymptomatic PSP; among these, eight students eventually underwent an invasive
      therapy. CONCLUSIONS: The prevalence of asymptomatic PSP among university
      students was as high as 0.042%. In addition to known risk factors for
      conventional PSP, greater height growth was a risk factor for asymptomatic PSP.
      Careful follow-up is very important because a considerable number of patients
      with mild lung collapse eventually require an invasive medical procedure.

PMID- 29216863
TI  - CCL5-CCR5 interactions modulate metabolic events during tumor onset to promote
      tumorigenesis.
AB  - BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces
      the proliferation and survival of breast cancer cells in a mechanistic target of
      rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated
      increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative
      human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle
      T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo
      tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in
      the context of regulating tumor metabolism. Additionally, we employed Matrix
      Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance
      Mass Spectrometry imaging (MALDI-FTICR-MSI) to evaluate tumor utilization of
      cellular metabolites. RESULTS: We provide evidence that, in the absence of CCR5,
      the early events associated with rapid tumor growth in the MMTV-PyMT mouse model
      of spontaneous breast cancer development, are diminished, as demonstrated by a
      delay in tumor onset. In tumor transplant studies into immunocompromised mice we
      identify a direct correlation between reduced tumor proliferation and decreased
      metabolic activity, specifically associated with tumor expression of CCR5. The
      reduction in tumorigenesis is accompanied by decreases in glucose uptake, glucose
      transporter-1 (GLUT-1) cell surface expression, intracellular ATP and lactate
      levels, as well as reduced CCL5 production. Using MALDI-FTICR-MS, we show that
      the rapid early tumor growth of CCR5+/+ triple negative breast cancer cells in
      vivo is attributable to increased levels of glycolytic intermediates required for
      anabolic processes, in contrast to the slower growth rate of their corresponding
      CCR5-/- cells, that exhibit reduced glycolytic metabolism. CONCLUSIONS: These
      findings suggest that CCL5-CCR5 interactions in the tumor microenvironment
      modulate metabolic events during tumor onset to promote tumorigenesis.

PMID- 29216864
TI  - Diagnostic value of interleukins for tuberculous pleural effusion: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The ability of interleukins (ILs) to differentiate tuberculous
      pleural effusion from other types of effusion is controversial. The aim of our
      study was to summarize the evidence for its use of ruling out or in tuberculous
      pleural effusion. METHODS: Two investigators independently searched PubMed,
      EMBASE, Web of Knowledge, CNKI, WANFANG, and WEIPU databases to identify studies
      assessing diagnostic role of ILs for tuberculous pleural effusion published up to
      January, 2017. Study quality was assessed using Quality Assessment of Diagnostic
      Accuracy Studies-2. The pooled diagnostic sensitivity and specificity of ILs were
      calculated by using Review Manager 5.3. Area under the summary receiver operating
      characteristic curve (AUC) was used to summarize the overall diagnostic
      performance of individual markers. RESULTS: Thirty-eight studies met our
      inclusion criteria. Pooled sensitivity, specificity and AUC for chosen ILs were
      as follows: IL-2, 0.67,0.76 and 0.86; IL-6, 0.86, 0.84 and 0.90; IL-12, 0.78,
      0.83 and 0.86; IL-12p40, 0.82,0.65 and 0.76; IL-18, 0.87, 0.92 and 0.95; IL-27,
      0.93, 0.95 and 0.95; and IL-33, 0.84, 0.80 and 0.88. CONCLUSIONS: Some of these
      ILs may assist in diagnosing tuberculous pleural effusion, though no single IL is
      likely to show adequate sensitivity or specificity on its own. Further studies on
      a large scale with better study design should be performed to assess the
      diagnostic potential of ILs.

PMID- 29216865
TI  - Effect of Orthokeratology on myopia progression: twelve-year results of a
      retrospective cohort study.
AB  - BACKGROUND: Several studies reported the efficacy of orthokeratology for myopia
      control. Somehow, there is limited publication with follow-up longer than 3
      years. This study aims to research whether overnight orthokeratology influences
      the progression rate of the manifest refractive error of myopic children in a
      longer follow-up period (up to 12 years). And if changes in progression rate are
      found, to investigate the relationship between refractive changes and different
      baseline factors, including refraction error, wearing age and lens replacement
      frequency. In addition, this study collects long-term safety profile of overnight
      orthokeratology. METHODS: This is a retrospective study of sixty-six school-age
      children who received overnight orthokeratology correction between January 1998
      and December 2013. Thirty-six subjects whose baseline age and refractive error
      matched with those in the orthokeratology group were selected to form control
      group. These subjects were followed up at least for 12 months. Manifest
      refractions, cycloplegic refractions, uncorrected and best-corrected visual
      acuities, power vector of astigmatism, corneal curvature, and lens replacement
      frequency were obtained for analysis. RESULTS: Data of 203 eyes were derived from
      66 orthokeratology subjects (31 males and 35 females) and 36 control subjects (22
      males and 14 females) enrolled in this study. Their wearing ages ranged from 7
      years to 16 years (mean +/- SE, 11.72 +/- 0.18 years). The follow-up time ranged
      from 1 year to 13 years (mean +/- SE, 6.32 +/- 0.15 years). At baseline, their
      myopia ranged from -0.5 D to -8.0 D (mean +/- SE, -3.70 +/- 0.12 D), and
      astigmatism ranged from 0 D to -3.0 D (mean +/- SE, -0.55 +/- 0.05 D). Comparing
      with control group, orthokeratology group had a significantly (p < 0.001) lower
      trend of refractive error change during the follow-up periods. According to the
      analysis results of GEE model, greater power of astigmatism was found to be
      associated with increased change of refractive error during follow-up years.
      CONCLUSIONS: Overnight orthokeratology was effective in slowing myopia
      progression over a twelve-year follow-up period and demonstrated a clinically
      acceptable safety profile. Initial higher astigmatism power was found to be
      associated with increased change of refractive error during follow-up years.

PMID- 29216866
TI  - Cross sectional study of serum selenium concentration and esophageal squamous
      dysplasia in western Kenya.
AB  - BACKGROUND: Low serum selenium status has been associated with increased risk of
      esophageal squamous cell carcinoma (ESCC). East Africa is a region of high ESCC
      incidence and is known to have low soil selenium levels, but this association has
      not previously been evaluated. In this study we assessed the association of serum
      selenium concentration and the prevalence of esophageal squamous dysplasia (ESD),
      the precursor lesion of ESCC, in a cross-sectional study of subjects from Bomet,
      Kenya. METHODS: 294 asymptomatic adult residents of Bomet, Kenya completed
      questionnaires and underwent endoscopy with Lugol's iodine staining and biopsy
      for detection of ESD. Serum selenium concentrations were measured by instrumental
      neutron activation analysis. Odds ratios (OR) and confidence intervals (95% CI)
      for associations between serum selenium and ESD were calculated using
      unconditional logistic regression. RESULTS: The mean serum selenium concentration
      was 85.5 (+/-28.3) MUg/L. Forty-two ESD cases were identified (14% of those
      screened), including 5 (12%) in selenium quartile 1 (Q1), 5 (12%) in Q2, 15 (36%)
      in Q3, and 17 (40%) in Q4. Higher serum selenium was associated with prevalence
      of ESD (Q4 vs Q1: OR: 3.03; 95% CI: 1.05-8.74) and this association remained
      after adjusting for potential confounders (Q4 vs Q1: OR: 3.87; 95% CI: 1.06
      14.19). CONCLUSION: This is the first study to evaluate the association of serum
      selenium concentration and esophageal squamous dysplasia in an African population
      at high risk for ESCC. We found a positive association between higher serum
      selenium concentration and prevalence of ESD, an association contrary to our
      original hypothesis. Further work is needed to better understand the role of
      selenium in the etiology of ESCC in this region, and to develop effective ESCC
      prevention and control strategies.

PMID- 29216867
TI  - Protein kinase C alpha enhances migration of breast cancer cells through FOXC2
      mediated repression of p120-catenin.
AB  - BACKGROUND: Despite recent advances in the diagnosis and treatment of breast
      cancer, metastasis remains the main cause of death. Since migration of tumor
      cells is considered a prerequisite for tumor cell invasion and metastasis, a
      pressing goal in tumor biology has been to elucidate factors regulating their
      migratory activity. Protein kinase C alpha (PKCalpha) is a serine-threonine
      protein kinase implicated in cancer metastasis and associated with poor prognosis
      in breast cancer patients. In this study, we set out to define the signaling axis
      mediated by PKCalpha to promote breast cancer cell migration. METHODS: OncomineTM
      overexpression analysis was used to probe for PRKCA (PKCalpha) and FOXC2
      expression in mRNA datasets. The heat map of PRKCA, FOXC2, and CTNND1 were
      obtained from the UC Santa Cruz platform. Survival data were obtained by PROGgene
      and available at http://www.compbio.iupui.edu/proggene . Markers for EMT and
      adherens junction were assessed by Western blotting and quantitative polymerase
      chain reaction. Effects of PKCalpha and FOXC2 on migration and invasion were
      assessed in vitro by transwell migration and invasion assays respectively.
      Cellular localization of E-cadherin and p120-catenin was determined by
      immunofluorescent staining. Promoter activity of p120-catenin was determined by
      dual luciferase assay using a previously validated p120-catenin reporter
      construct. Interaction between FOXC2 and p120-catenin promoter was verified by
      chromatin immunoprecipitation assay. RESULTS: We determined that PKCalpha
      expression is necessary to maintain the migratory and invasive phenotype of both
      endocrine resistant and triple negative breast cancer cell lines. FOXC2 acts as a
      transcriptional repressor downstream of PKCalpha, and represses p120-catenin
      expression. Consequently, loss of p120-catenin leads to destabilization of E
      cadherin at the adherens junction. Inhibition of either PKCalpha or FOXC2 is
      sufficient to rescue p120-catenin expression and trigger relocalization of p120
      catenin and E-cadherin to the cell membrane, resulting in reduced tumor cell
      migration and invasion. CONCLUSIONS: Taken together, these results suggest that
      breast cancer metastasis may partially be controlled through PKCalpha/FOXC2
      dependent repression of p120-catenin and highlight the potential for PKCalpha
      signal transduction networks to be targeted for the treatment of endocrine
      resistant and triple negative breast cancer.

PMID- 29216868
TI  - Socio-demographic determinants and effect of structured personal diabetes care: a
      19-year follow-up of the randomized controlled study diabetes Care in General
      Practice (DCGP).
AB  - BACKGROUND: We investigated how four aspects of socio-demography influence the
      effectiveness of an intervention with structured personal diabetes care on long
      term outcomes. METHODS: The Diabetes Care in General Practice (DCGP) study is a
      cluster-randomized trial involving a population-based sample of 1381 patients
      with newly diagnosed type 2-diabetes mellitus. We investigated how education,
      employment, cohabitation status and residence influenced the effectiveness of 6
      years of intervention with structured personal diabetes care, resembling present
      day recommendations. Outcomes were incidence of any diabetes-related endpoint and
      death during 19 years after diagnosis, and cardiovascular risk factors,
      behaviour, attitudes and process-of-care variables 6 years after diagnosis.
      RESULTS: Structured personal care reduced the risk of any diabetes-related
      endpoint and the effect of the intervention was modified by geographical area
      (interaction p = 0.034) with HR of 0.71 (95%CI: 0.60-0.85) and of 1.07 (95%CI:
      0.77-1.48), for patients in urban and rural areas, respectively. Otherwise, there
      was no effect modification of education, employment and civil status on the
      intervention for the final endpoints. There were no noticeable socio-demographic
      differences in the effect of the intervention on cardiovascular risk factors,
      behaviour, attitudes, and process-of-care. CONCLUSION: Structured personal care
      reduced the aggregate outcome of any diabetes-related endpoint and independent of
      socio-demographic factors similar effect on cardiovascular risk factors,
      behaviour, attitudes and process of care, but the intervention did not change the
      existing inequity in mortality and morbidity. Residence modified the uptake of
      the intervention with patients living in urban areas having more to gain of the
      intervention than rural patients, further investigations is warranted. TRIAL
      REGISTRATION: ClinicalTrials.gov registration no. NCT01074762 (February 24,
      2010).

PMID- 29216869
TI  - Horizontal ridge reconstruction of the anterior maxilla using customized
      allogeneic bone blocks with a minimally invasive technique - a case series.
AB  - BACKGROUND: Different surgical procedures have been proposed to achieve
      horizontal ridge reconstruction of the anterior maxilla; all these procedures,
      however, require bone replacement materials to be adapted to the bone defect at
      the time of implantation, resulting in complex and time-consuming procedures. The
      purpose of this study was to describe how to use a 3D printed hardcopy model of
      the maxilla to prepare customized milled bone blocks, to be adapted on the bone
      defect areas using a minimally invasive subperiosteal tunneling technique.
      METHODS: Cone beam computed tomography (CBCT) images of the atrophic maxilla of
      six patients were acquired and modified into 3D reconstruction models. Data were
      transferred to a 3D printer and solid models were fabricated using autoclavable
      nylon polyamide. Before the surgery, freeze-dried cortico-cancellous blocks were
      manually milled and adapted on the 3D printed hardcopy models of the maxillary
      bone, in order to obtain customized allogeneic bone blocks. RESULTS: In total,
      eleven onlay customized allogeneic bone grafts were prepared and implanted in 6
      patients, using a minimally invasive subperiosteal tunneling technique. The
      scaffolds closely matched the shape of the defects: this reduced the operation
      time and contributed to good healing. The patients did not demonstrate adverse
      events such as inflammation, dehiscence or flap re-opening during the recovery
      period; however, one patient experienced scaffold resorption, which was likely
      caused by uncontrolled motion of the removable provisional prosthesis. Following
      a 6 month healing period, CBCT was used to assess graft integration, which was
      followed by insertion of implants into the augmented areas. Prosthetic
      restorations were placed 4 months later. CONCLUSIONS: These observations suggest
      that customized bone allografts can be successfully used for horizontal ridge
      reconstruction of the anterior maxilla: patients demonstrated reduced morbidity
      and decreased total surgery time. Further studies on a larger sample of patients,
      with histologic evaluation and longer follow-up are needed to confirm the present
      observations.

PMID- 29216870
TI  - Prevalence and severity of menopause symptoms among perimenopausal and
      postmenopausal women aged 30-49 years in Gulele sub-city of Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: Menopause is a natural phenomenon occurring as women approach middle
      age. It is characterized by declining of ovarian function and onset of the last
      menstrual period and subsequent 12-month cessation of menstruation. Due to a
      growing aging population and longer life expectancies, sub-Saharan African women
      will spend a significant portion of their lives in postmenopause. Menopausal
      symptom research has been primarily conducted on Caucasian women from high-income
      countries. Understanding menopause symptom prevalence and perceptions among
      diverse women in Ethiopia will better inform reproductive health care. METHODS:
      We conducted a multi-stage, cross-sectional study on 226 perimenopausal and
      postmenopausal women aged 30-49 years in Gulele sub-city of Addis Ababa,
      Ethiopia. Data on socio-demographic characteristics, menopausal status and an 11
      item Menopause Rating Scale (MRS) were collected using interviewer-administered
      questionnaire. Statistical analyses consisted of descriptive data and chi-squared
      analyses. RESULTS: Study participants were 40.4 +/- 5.9 years, on average, with
      the majority married, educated at secondary school level, and comprised different
      ethnicities and wealth tertiles. The most prevalent types of menopausal symptoms
      reported from the MRS were from somatic subscale (65.9%) while psychological
      (46.0%) and urogenital subscale symptoms (30.5%) were also prevalent. The most
      commonly reported individual symptoms were: hot flushes (65.9% (95% CI: 59.4%
      72.1%)), difficulty falling asleep (49.6% (95% CI: 42.9%-56.3%)), depressive mood
      (46.0% (95% CI: 39.4%-52.8%)), irritability (45.1% (95% CI: 38.5%-51.9%)), and
      anxiety (39.8% (95% CI: 33.4%-46.5%)). Each of the somatic, psychological, and
      urogenital MRS subscale scores were higher among postmenopausal women compared to
      perimenopausal women. Women self-reported differing severity levels of symptoms
      with high severity reported in 8.4% of total MRS, 1.3% of somatic, 10.6% of
      psychological, and 8.4% of urogenital scales. CONCLUSIONS: Our study provides the
      first presentation of menopausal symptoms among perimenopausal and postmenopausal
      women in the Gulele sub-city of Addis Ababa, Ethiopia. We capture the prevalence
      of menopausal symptoms experienced as well as self-rated severity through the
      MRS. Our findings reflect menopausal symptoms in our specific study population
      and have been found to be consistent with previous international research.

PMID- 29216871
TI  - Mental health literacy among pediatric hospital staff in the United Arab
      Emirates.
AB  - BACKGROUND: In the United Arab Emirates (UAE) 35% of the population are aged 0-24
      years. A significant proportion of these young people are living with chronic
      conditions (e.g., asthma, type 1 diabetes, cardiac conditions, and genetically
      transmitted conditions such as thalassemia and cystic fibrosis). This group has
      increased vulnerability to developmental delays and mental health problems, and
      is increasingly coming to the attention of service providers in mainstream
      schools, primary healthcare centers, and pediatric hospitals. Despite the
      government directing attention to improving the mental health of the UAE
      population, there is concern that mental health services are not growing at the
      rate needed to meet the mental health needs of children and young people with
      chronic conditions. METHOD: A cross sectional survey design was used to determine
      the mental health literacy of nurses and other healthcare professionals working
      with children with chronic illnesses. Participants completed a culturally-adapted
      mental health literacy questionnaire comprising three vignettes of fictional
      characters meeting diagnostic criteria for posttraumatic stress disorder,
      psychosis, and depression with suicidal thoughts. Participants also completed the
      Kessler Psychological Distress Scale (K10). RESULTS: Participants were 317
      healthcare professionals from across the UAE. The majority were nurses. Correct
      identification of the diagnosis for each vignette was limited, with the highest
      level of accuracy achieved for the psychosis vignette (n = 113, 54.3%). Accurate
      identification of appropriate evidence-based interventions was also limited. K10
      scores indicated 40% of participants had moderate to high levels of psychological
      distress. CONCLUSIONS: These findings are concerning and provide important data
      to inform the development of undergraduate and continuing education programs for
      nurses. The K10 scores suggest healthcare professionals are under considerable
      stress, highlighting the need to support healthcare professionals who experience
      multiple psychosocial stressors.

PMID- 29216872
TI  - Late-onset diffuse lamellar keratitis 4 years after femtosecond laser-assisted
      small incision lenticule extraction: a case report.
AB  - BACKGROUND: To report a first case of late-onset diffuse lamellar keratitis (DLK)
      occurring 4 years after femtosecond laser-assisted small incision lenticule
      extraction (SMILE). CASE PRESENTATION: A 41-year-old man who underwent SMILE 4
      years prior developed DLK in the right eye 1 day after he was struck in the eye
      by a finger while playing with his son. Slim-lamp microscopy and anterior segment
      optical coherence tomography (AS-OCT) were used to evaluate the cornea of the
      right eye. Slit-lamp examination of the right eye revealed epithelial exfoliation
      and stage 3 DLK with diffuse, dot-like, granular haze in the interface between
      the cap and stromal bed. After intensive treatment with topical corticosteroids,
      the DLK resolved and corneal transparency was achieved. CONCLUSIONS: This case
      indicates that DLK can occur several years after SMILE. Ocular trauma may be a
      risk factor for the development of DLK. The prognosis is usually favorable with
      early diagnosis and treatment with topical corticosteroids.

PMID- 29216873
TI  - Community-based specialist palliative care is associated with reduced hospital
      costs for people with non-cancer conditions during the last year of life.
AB  - BACKGROUND: Community-based palliative care is associated with reduced hospital
      costs for people dying from cancer. It is unknown if reduced hospital costs are
      universal across multiple life-limiting conditions amenable to palliative care.
      The aim of this study was to determine if community-based palliative care
      provided to people dying from non-cancer conditions was associated with reduced
      hospital costs in the last year of life and how this compared with people dying
      from cancer. METHOD: A retrospective population-based cohort study of all
      decedents in Western Australia who died January 2009 to December 2010 from a life
      limiting condition considered amenable to palliative care. Hospital costs were
      assigned to each day of the last year of life for each decedent with a zero cost
      applied to days not in hospital. Day-specific hospital costs averaged over all
      decedents (cohort averaged) and decedents in hospital only (inpatient averaged)
      were estimated. Two-part models and generalised linear models were used. RESULTS:
      The cohort comprised 12,764 decedents who, combined, spent 451,236 (9.7%) days of
      the last year of life in hospital. Overall, periods of time receiving community
      based specialist palliative care were associated with a 27% decrease from A$112
      (A$110-A$114) per decedent per day to $A82 (A$78-A$85) per decedent per day of CA
      hospital costs. Community-based specialist palliative care was also associated a
      reduction of inpatient averaged hospital costs of 9% (7%-10%) to A$1030 per
      hospitalised decedent per day. Hospital cost reductions were observed for
      decedents with organ failures, chronic obstructive pulmonary disease, Alzheimer's
      disease, Parkinson's disease and cancer but not for motor neurone disease. Cost
      reductions associated with community-based specialist palliative care were
      evident 4 months before death for decedents with cancer and by one to 2 months
      before death for decedents dying from other conditions. CONCLUSION: Community
      based specialist palliative care was associated with hospital cost reductions
      across multiple life-limiting conditions.

PMID- 29216874
TI  - Factors influencing the experience of sexual and reproductive healthcare for
      female adolescents with perinatally-acquired HIV: a qualitative case study.
AB  - BACKGROUND: Young people living with perinatally-acquired HIV require age
      appropriate support regarding sex and relationships as they progress towards
      adulthood. HIV affects both genders but evidence suggests that young women are
      particularly vulnerable to sexual abuse and more prone to engaging in sexual
      behaviours to meet their daily survival needs. This can result in poor sexual and
      reproductive health (SRH) outcomes. HIV services in Malawi provide support for
      young women's HIV-related clinical needs, but it is unclear whether there is
      sufficient provision for their SRH needs as they become adults. This paper
      explores the sex and relationship experiences of young women growing up with
      perinatally-acquired HIV in order to understand how to improve SRH care and
      associated outcomes. METHODS: A qualitative case study approach was adopted in
      which each 'case' comprised a young woman (15-19 years) with perinatally acquired
      HIV, a nominated caregiver and service provider. Participants were purposively
      selected from three multidisciplinary centres providing specialised
      paediatric/adolescent HIV care in Malawi. Data was collected for 14 cases through
      in-depth interviews (i.e. a total of 42 participants) and analysed using within
      case and cross-case approaches. The interviews with adolescents were based on an
      innovative visual method known as 'my story book' which encouraged open
      discussion on sensitive topics. RESULTS: Young women reported becoming sexually
      active at an early age for different reasons. Some sought a sense of intimacy,
      love, acceptance and belonging in these relationships, noting that they lacked
      this at home and/or within their peer groups. For others, their sexual activity
      was more functional - related to meeting survival needs. Young women reported
      having little control over negotiating safer sex or contraception. Their priority
      was preventing unwanted pregnancies yet several of the sample already had babies,
      and transfer to antenatal services created major disruptions in their HIV care.
      In contrast, caregivers and nurses regarded sexual activity from a clinical
      perspective, fearing onward transmission of HIV and advocating abstinence or
      condoms where possible. In addition, a cultural silence rooted in dominant
      religious and traditional norms closed down possibilities for discussion about
      sexual matters and prevented young women from accessing contraception.
      CONCLUSION: The study has shown how young women, caregivers and service providers
      have contrasting perspectives and priorities around SRH care. Illumination of
      these differences highlights a need for service improvement. It is suggested that
      young women themselves are involved in future service improvement initiatives to
      encourage the development of culturally and socially acceptable pathways of care.

PMID- 29216875
TI  - Pulmonary inflammatory Myofibroblastic tumor indistinguishable from tuberculosis:
      a case report in a five-year-old child with hemoptysis.
AB  - BACKGROUND: Pulmonary inflammatory myofibroblastic tumor (PIMT) is a rare disease
      in China and its incidence is much lower than that of tuberculosis. PIMT accounts
      for only 0.04-1.2% of all lung tumors. PIMT can occurs in any age and nearly
      every part of the body. The clinical symptoms and radiological features of PIMT
      are nonspecific. Diagnosis is only made on the basis of histopathologic or
      immunohistochemical evaluation of the postoperation resected tissue. The
      therapeutic approach to PIMT should rely mainly on complete surgical resection.
      CASE PRESENTATION: We report a case of PIMT with hemoptysis. The girl was
      misdiagnosed with tuberculosis and treated with anti-tuberculous drugs for a long
      period of time. A right upper and middle lobectomy was performed and further
      assessment of the tissue demonstrated a pathologic diagnosis of PIMT.
      CONCLUSIONS: Despite a high incidence of tuberculosis, we must consider the
      possibility of PIMTs in such cases to prevent misdiagnosis and mistreatment.

PMID- 29216876
TI  - Refugees' experiences of healthcare in the host country: a scoping review.
AB  - BACKGROUND: During the last years, Europe experienced an increase in immigration
      due to a variety of worldwide wars and conflicts, which in turn resulted in a
      greater number of physical and mental health issues present among the refugees.
      These factors place high demands not only on the refugees, but also on healthcare
      professionals who meet the refugees in different situations. Information about
      the refugees' experiences of the healthcare systems in their host countries is
      urgently needed to improve the quality of healthcare delivered, as well as to
      provide opportunities for better access. The aim of this scoping review is to
      compile research about the experiences that the refugees have with the healthcare
      systems in their host countries. METHODS: This study was conducted as a scoping
      review and the methodology is derived from Levac et al. and with inspiration from
      the framework of Arksey & O'Malley. A systematic article search was done in
      Medline, Cinahl and Psychinfo. A total of 619 articles were found in the search
      and finally 26 articles met the inclusion criteria and were included. RESULTS:
      The results show that communication between healthcare professionals and refugees
      is important, however, insufficient language knowledge acts as an effective
      communication barrier. There is a need for more information to be given to the
      refugees about the reception country's healthcare system in both oral and written
      formats, as well as the right to healthcare. Support from healthcare
      professionals is also important for refugees to have a positive experience with
      healthcare. In some of the studies included, refugees experienced discrimination
      due to low proficiency in the language of the host country, and/or because of
      their race or accent, which shows that culturally appropriate healthcare is
      needed for them. CONCLUSIONS: Since refugees are suffering from poor mental and
      physical health and could therefore be at a greater risk of morbidity and
      mortality in comparison to the rest of the population of the host country, there
      is an urgent need for improvements in communication, interpretation, support, and
      deliverance of culturally appropriate healthcare.

PMID- 29216877
TI  - Donor-funded project's sustainability assessment: a qualitative case study of a
      results-based financing pilot in Koulikoro region, Mali.
AB  - BACKGROUND: Results-based financing (RBF) is emerging as a new alternative to
      finance health systems in many African countries. In Mali, a pilot project was
      conducted to improve demand and supply of health services through financing
      performance in targeted services. No study has explored the sustainability
      process of such a project in Africa. This study's objectives were to understand
      the project's sustainability process and to assess its level of sustainability.
      METHODS: Sustainability was examined through its different determinants, phases,
      levels and contexts. These were explored using qualitative interviews to discern,
      via critical events, stakeholders' ideas regarding the project's sustainability.
      Data collection sites were chosen with the participation of different
      stakeholders, based on a variety of criteria (rural/urban settings, level of
      participation, RBF participants still present, etc.). Forty-nine stakeholders
      were then interviewed in six community health centres and two referral health
      centres (from 11/12/15 to 08/03/16), including health practitioners,
      administrators, and those involved in implementing and conceptualizing the
      program (government and NGOs). A theme analysis was done with the software (c)
      QDA Miner according to the study's conceptual framework. RESULTS: The results of
      this project show a weak level of sustainability due to many factors. While some
      gains could be sustained (ex.: investments in long-term resources, high
      compatibility of values and codes, adapted design to the implementations
      contexts, etc.) other intended benefits could not (ex.: end of investments, lack
      of shared cultural artefacts around RBF, loss of different tasks and procedures,
      need of more ownership of the project by the local stakeholders). A lack of
      sustainability planning was observed, and few critical events were associated to
      phases of sustainability. CONCLUSIONS: While this RBF project aimed at increasing
      health agents' motivation through different mechanisms (supervision, investments,
      incentives, etc.), these results raise questions on what types of motivation
      could be more stable and what could be the place of local stakeholders in the
      project; all this with the aim of more sustained and efficient results.

PMID- 29216878
TI  - Adaptive phenotype drives resistance to androgen deprivation therapy in prostate
      cancer.
AB  - BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men
      worldwide, shows a broad spectrum of biological and clinical behaviour
      representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation
      therapy is the mainstay of treatment for advanced forms but after few years the
      majority of patients progress to castration-resistant prostate cancer (CRPC), a
      lethal form that poses considerable therapeutic challenges. METHODS: Western
      blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies
      were performed to characterize androgen resistant sublines phenotype in
      comparison to the parental cell line LNCaP. RNA microarray, mass spectrometry,
      integrative transcriptomic and proteomic differential analysis coupled with
      GeneOntology and multivariate analyses were applied to identify deregulated genes
      and proteins involved in CRPC evolution. RESULTS: Treating the androgen
      responsive LNCaP cell line for over a year with 10 MUM bicalutamide both in the
      presence and absence of 0.1 nM 5-alpha-dihydrotestosterone (DHT) we obtained two
      cell sublines, designated PDB and MDB respectively, presenting several analogies
      with CRPC. Molecular and functional analyses of PDB and MDB, compared to the
      parental cell line, showed that both resistant cell lines were PSA low/negative
      with comparable levels of nuclear androgen receptor devoid of activity due to
      altered phosphorylation; cell growth and survival were dependent on AKT and
      p38MAPK activation and PARP-1 overexpression; their malignant phenotype increased
      both in vitro and in vivo. Performing bioinformatic analyses we highlighted
      biological processes related to environmental and stress adaptation supporting
      cell survival and growth. We identified 15 proteins that could direct androgen
      resistance acquisition. Eleven out of these 15 proteins were closely related to
      biological processes involved in PCa progression. CONCLUSIONS: Our models suggest
      that environmental factors and epigenetic modulation can activate processes of
      phenotypic adaptation driving drug-resistance. The identified key proteins of
      these adaptive phenotypes could be eligible targets for innovative therapies as
      well as molecules of prognostic and predictive value.

PMID- 29216879
TI  - Anti-diabetic potential of Sapium ellipticum (Hochst) Pax leaf extract in
      Streptozotocin(STZ)-induced diabetic Wistar rats.
AB  - BACKGOUND: Ethnobatanical survey associates Sapium ellipticum (SE) with
      antidiabetic usage among other medicinal functions in different parts of Africa.
      More importantly, previous studies on the plant extract in our laboratory showed
      that SE has significant effects on the activities of carbohydrate metabolizing
      enzymes such as glucokinase, glucose-6-phosphatase, alpha-amylase and alpha
      glucosidase. In view of these, the anti-diabetic potential of the plant leaf
      extract in streptozotocin (STZ)-induced diabetes rat model (Wistar strain) was
      examined. METHODS: Diabetes was induced in experimental animals via single
      intraperitoneal dose (55 mg/kg BW) of freshly prepared STZ. SE was evaluated at
      400 and 800 mg kg-1 of body weight (BW), against metformin (12 mgkg-1 BW).
      Treatments were done orally (p.o), twice daily at 8 h interval for a period of 21
      days. RESULTS: SE significantly reduced fasting blood glucose (FBG) level by 46.5
      and 44.4% (400 and 800 mg dosage respectively) compared to initial diabetic
      values. However, the effects were significantly lower than 72.6% glucose
      reduction produced by metformin. Hepatic and skeletal muscle glycogens were
      observed to increase by 27.06 and 12.55% respectively in SE-treated rats (800 mg
      dosage) compared to their corresponding values in diabetic control animals.
      Plasma and pancreatic insulin contents were also improved (31.77 and 52.34%
      respectively) by SE administration. The histopathological examination of the
      pancreas indicates beta cells regeneration in the treated animals, particularly
      in diabetic rats treated with 800 mg dosage of the extract compared to the
      diabetic control animals and metformin group. The presence of phenolic compounds
      namely amentoflavone, lupeol and luteolin-7-O-glucoside in SE as characterized
      and reported in our previous study is likely responsibly for the antidiabetic
      effects of the plant extract noted in the present study. CONCLUSION: The outcome
      of this study provides scientific basis in support of the medicinal relevance of
      SE and lend credence to its utilization in folk medicine for the treatment of
      diabetes and other oxidative stress-related ailments.

PMID- 29216880
TI  - Cost-effectiveness of Human Papilloma Virus (HPV) vaccination in Nigeria: a
      decision analysis using pragmatic parameter estimates for cost and programme
      coverage.
AB  - BACKGROUND: World Health Organisation recommends routine Human Papilloma Virus
      (HPV) vaccination for girls when its cost-effectiveness in the country or region
      has been duly considered. We therefore aimed to evaluate cost-effectiveness of
      HPV vaccination in Nigeria using pragmatic parameter estimates for cost and
      programme coverage, i.e. realistically achievable in the studied context.
      METHODS: A microsimulation frame-work was used. The natural history for cervical
      cancer disease was remodelled from a previous Nigerian model-based study. Costing
      was based on health providers' perspective. Disability adjusted life years
      attributable to cervical cancer mortality served as benefit estimate. Suitable
      policy option was obtained by calculating the incremental costs-effectiveness
      ratio. Probabilistic sensitivity analysis was used to assess parameter
      uncertainty. One-way sensitivity analysis was used to explore the robustness of
      the policy recommendation to key parameters alteration. Expected value of perfect
      information (EVPI) was calculated to determine the expected opportunity cost
      associated with choosing the optimal scenario or strategy at the maximum cost
      effectiveness threshold. RESULTS: Combination of the current scenario of
      opportunistic screening and national HPV vaccination programme (CS + NV) was the
      only cost-effective and robust policy option. However, CS + NV scenario was only
      cost-effective so far the unit cost of HPV vaccine did not exceed $5. EVPI
      analysis showed that it may be worthwhile to conduct additional research to
      inform the decision to adopt CS + NV. CONCLUSIONS: National HPV vaccination
      combined with opportunist cervical cancer screening is cost-effective in Nigeria.
      However, adoption of this strategy should depend on its relative efficiency when
      compared to other competing new vaccines and health interventions.

PMID- 29216882
TI  - Case report: surgical removal of a migrated needle in right ventricle of an
      intravenous drug user.
AB  - BACKGROUND: Illicit drug use has become an increasing public health and social
      concern in the past decades worldwide. Intravenous injection has an elevated risk
      of infection. Needle embolism is a rare complication of intravenous drug users,
      Retained broken needles can lead to local complications, such as infection, but
      they also have the potential to embolize to heart or lung, and lead to serious
      complications. METHOD: We reported a rare case of an intravenous drug user which
      a retained broken needle fragments in the inferior wall of the right ventricle.
      RESULTS: We performed a successful surgery and give our comments and
      recommendations for illicit drug use worldwide and in China. CONCLUSIONS: Illicit
      Drug use becomes a global problem because of its health and social harmfulness.
      To help drug addicts and provide prevention and treatment services are the
      obligations and responsibilities of all medical workers.

PMID- 29216881
TI  - Risks, benefits size and clinical implications of combined oral contraceptive use
      in women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex condition with high
      risk for dyslipidemia, dysglycemia, venous thromboembolism, cardiovascular
      disease and metabolic syndrome. Because the combined oral contraceptive (COC) use
      has also been associated with impaired fasting glucose, insulin resistance and
      increased risk of thromboembolism disease, it is rationale to think that the
      combination of oral contraceptive and PCOS could make it worse or increase the
      risks. OBJECTIVE: To examine the current data regarding potential additional
      risks and benefits of contraceptive use, highlights the major gap in knowledge
      for designing future studies and, when possible, suggests an adequate COC
      formulation for a determined PCOS phenotype. METHODS: English-language
      publications reporting on the influence of COCS in the development of venous
      thromboembolism in PCOS patients published until 2017 were searched using PubMed,
      Cochrane database, and hand search of references found in consulted articles.
      Ranges of collected data are given; the pooled data are presented as median and
      first and third quartiles. Wilcoxon signed-ranks test for paired samples was used
      to compare before-after original data. P value was set at 0.05. RESULTS: Most of
      COCs preparations significantly decrease androgens, and increase sex-hormone
      binding globulin. Therefore, the benefits of COCs are clear in patients with
      proved hyperandrogenemia. Regarding the impact of COCs on carbohydrate metabolism
      of PCOS subjects, the data were inconsistent but they tended to show no
      additional risk. Regarding lipids, most COCs consistently increased high-density
      lipoprotein cholesterol, triglycerides and total cholesterol concentrations but
      the clinical implications of these changes need additional studies. CONCLUSION:
      The review showed consistent beneficial effect of COCs, particularly for
      hyperandrogenemic PCOS patients. The benefit size of COC's use by
      normoandrogenemic PCOS patients is uncertain and need more investigation. The
      effects of COC use on carbohydrate metabolism of women with PCOS are still
      unresolved since most studies are observational but the current results
      demonstrated that COCs do not make their levels worse and may improve insulin
      sensitivity. The impact of COCs on lipids of PCOS patients seems to be clearer
      and most preparations increase total cholesterol, high-density lipoprotein
      cholesterol and triglycerides. In summary, it is important to balance the
      potential benefits and risks of the COCs individually before prescribing them for
      PCOS women.

PMID- 29216883
TI  - Transplant eligibility for patients with affective and psychotic disorders: a
      review of practices and a call for justice.
AB  - BACKGROUND: The scarcity of human organs requires the transplant community to
      make difficult allocation decisions. This process begins at individual medical
      centers, where transplant teams decide which patients to place on the transplant
      waiting list. Each transplant center utilizes its own listing criteria to
      determine if a patient is eligible for transplantation. These criteria have
      historically considered preexisting affective and psychotic disorders to be
      relative or absolute contraindications to transplantation. While attitudes within
      the field appear to be moving away from this practice, there is no data to
      confirm that eligibility criteria have changed. MAIN BODY: There are no
      nationwide guidelines detailing the manner in which affective and psychotic
      disorders should impact transplant eligibility. Individual transplant centers
      thus form their own transplant eligibility criteria, resulting in significant
      inter-institution variability. Data from the 1990s indicates that the majority of
      transplant programs considered certain psychiatric illnesses, such as active
      schizophrenia, to be absolute contraindications to transplantation. A review of
      literature reveals that no comprehensive data has been collected on the topic
      since that time. Furthermore, the limited data available about current practices
      suggests that psychiatric illness continues to be viewed as a contraindication to
      transplantation at some transplant centers. In light of this finding, we review
      psychiatric literature that examines the impact of affective and psychotic
      disorders on transplant outcomes and conclude that the presence of these
      disorders is not an accurate predictor of transplant success. We then discuss the
      requirements of justice as they relate to the creation of a just organ allocation
      system. CONCLUSION: We conclude that transplant eligibility criteria that exclude
      patients with affective and psychotic disorders on the basis of their psychiatric
      diagnosis alone are unjust. Just listing criteria must incorporate only those
      factors that have a causative effect on posttransplant morbidity and mortality.
      Justice also demands that we eliminate current inter-institution practice
      variations in favor of national transplant eligibility criteria. Given the
      limited data available about current practices, we call for an updated study
      investigating the manner in which affect and psychotic disorders impact
      transplant eligibility determinations.

PMID- 29216884
TI  - Intensity modulated radiation therapy and surgery for Management of
      Retroperitoneal Sarcomas: a single-institution experience.
AB  - BACKGROUND: Peri-operative radiation of retroperitoneal sarcomas (RPS) is an
      important component of multidisciplinary treatment. All retrospective series thus
      far included patients treated with older radiation therapy (RT) techniques
      including 2D and 3DRT. Intensity modulated radiation therapy (IMRT) allows for
      selective dose escalation while sparing adjacent organs. We therefore report the
      first series of patients with RPS treated solely with IMRT, surgery and
      chemotherapy. We hypothesized that IMRT would permit safe dose escalation and
      superior rates of local control (LC) in this high-risk patient population.
      METHODS: Thirty patients with RPS treated with curative intent between 2006 and
      2015 were included in this retrospective study. RT was administered either pre-
      or post-operatively and IMRT was used in all patients. Statistical comparisons,
      LC, distant metastasis (DM), and overall survival (OS) were calculated by Kaplan
      Meier analysis and univariate Cox regression. RESULTS: Median follow-up time
      after completion of RT was 36 months (range 1.4-112). Median tumor size was 14 cm
      (range 3.6 - 28 cm). The most prevalent histologies were liposarcoma in 10 (33%)
      patients and leiomyosarcoma in 10 (33%) with 21 patients (70%) having high-grade
      disease. Twenty-eight (93%) patients had surgical resection with 47% having
      positive margins. Chemotherapy was administered in 9 (30%) patients. RT was
      delivered pre-operatively in 11 (37%) patients, and post-operatively in 19 (63%)
      with 60% of patients receiving a simultaneous integrated boost. Pre-operative
      median RT dose to the high-risk area was 55 Gy (range, 43-66 Gy) while median
      post-operative dose was 60.4 Gy (range, 45-66.6 Gy). There was one acute grade 3
      and one late grade 3 toxicity and no grade 4 or 5 toxicities. Three year
      actuarial LC, freedom from DM, and OS rates were 84%, 64%, and 68% respectively.
      Positive surgical margins were associated with a higher risk of local recurrence
      (p = 0.02) and decreased OS (p = 0.04). Pre-operative RT was associated with
      improved LC (p = 0.1) with a 5-year actuarial LC of 100%. Administration of
      chemotherapy, timing of RT, histology or grade was not predictive of OS.
      CONCLUSIONS: Patients with RPS treated with peri-operative IMRT at our
      institution had excellent local control and low incidences of toxicity.

PMID- 29216885
TI  - A systematic approach to ultrasound-guided central venous catheter placement
      desirable modifications.

PMID- 29216886
TI  - A mixed-methods study of system-level sustainability of evidence-based practices
      in 12 large-scale implementation initiatives.
AB  - BACKGROUND: In recent decades, evidence-based practices (EBPs) have been broadly
      promoted in community behavioural health systems in the United States of America,
      yet reported EBP penetration rates remain low. Determining how to systematically
      sustain EBPs in complex, multi-level service systems has important implications
      for public health. This study examined factors impacting the sustainability of
      parent-child interaction therapy (PCIT) in large-scale initiatives in order to
      identify potential predictors of sustainment. METHODS: A mixed-methods approach
      to data collection was used. Qualitative interviews and quantitative surveys
      examining sustainability processes and outcomes were completed by participants
      from 12 large-scale initiatives. RESULTS: Sustainment strategies fell into nine
      categories, including infrastructure, training, marketing, integration and
      building partnerships. Strategies involving integration of PCIT into existing
      practices and quality monitoring predicted sustainment, while financing also
      emerged as a key factor. CONCLUSIONS: The reported factors and strategies
      impacting sustainability varied across initiatives; however, integration into
      existing practices, monitoring quality and financing appear central to high
      levels of sustainability of PCIT in community-based systems. More detailed
      examination of the progression of specific activities related to these strategies
      may aide in identifying priorities to include in strategic planning of future
      large-scale initiatives. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02543359 ;
      Protocol number PRO12060529.

PMID- 29216887
TI  - Comparative analyses of DHA-Phosphatidylcholine and recombination of DHA
      Triglyceride with Egg-Phosphatidylcholine or Glycerylphosphorylcholine on DHA
      repletion in n-3 deficient mice.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) is important for optimal neurodevelopment
      and brain function during the childhood when the brain is still under
      development. METHODS: The effects of DHA-Phosphatidylcholine (DHA-PC) and the
      recombination of DHA-Triglyceride with egg PC (DHA-TG + PC) or alpha
      Glycerylphosphorylcholine (DHA-TG + alpha-GPC) were comparatively analyzed on DHA
      recovery and the DHA accumulation kinetics in tissues including cerebral cortex,
      erythrocyte, liver, and testis were evaluated in the weaning n-3 deficient mice.
      RESULTS: The concentration of DHA in weaning n-3 deficient mice could be
      recovered rapidly by dietary DHA supplementation, in which DHA-PC exhibited the
      better efficacy than the recombination of DHA-Triglyceride with egg PC or alpha
      GPC. Interestingly, DHA-TG + alpha-GPC exhibited the greater effect on DHA
      accumulation than DHA-TG + PC in cerebral cortex and erythrocyte (p < 0.05),
      which was similar to DHA-PC. Meanwhile, DHA-TG + PC showed a similar effect to
      DHA-PC on DHA repletion in testis, which was better than that of DHA-TG + alpha
      GPC (p < 0.05). CONCLUSION: We concluded that different forms of DHA supplements
      could be applied targetedly based on the DHA recovery in different tissues,
      although the supplemental effects of the recombination of DHA-Triglyceride with
      egg PC or alpha-GPC were not completely equivalent to that of DHA-PC, which could
      provide some references to develop functional foods to support brain development
      and function.

PMID- 29216888
TI  - Telomere heterogeneity linked to metabolism and pluripotency state revealed by
      simultaneous analysis of telomere length and RNA-seq in the same human embryonic
      stem cell.
AB  - BACKGROUND: Telomere length heterogeneity has been detected in various cell
      types, including stem cells and cancer cells. Cell heterogeneity in pluripotent
      stem cells, such as embryonic stem cells (ESCs), is of particular interest;
      however, the implication and mechanisms underlying the heterogeneity remain to be
      understood. Single-cell analysis technology has recently been developed and
      effectively employed to investigate cell heterogeneity. Yet, methods that can
      simultaneously measure telomere length and analyze the global transcriptome in
      the same cell have not been available until now. RESULTS: We have established a
      robust method that can simultaneously measure telomere length coupled with RNA
      sequencing analysis (scT&R-seq) in the same human ESC (hESC). Using this method,
      we show that telomere length varies with pluripotency state. Compared to those
      with long telomere, hESCs with short telomeres exhibit the lowest expressions of
      TERF1/TRF1, and ZFP42/REX1, PRDM14 and NANOG markers for pluripotency, suggesting
      that these hESCs are prone to exit from the pluripotent state. Interestingly,
      hESCs ubiquitously express NOP10 and DKC1, stabilizing components of telomerase
      complexes. Moreover, new candidate genes, such as MELK, MSH6, and UBQLN1, are
      highly expressed in the cluster of cells with long telomeres and higher
      expression of known pluripotency markers. Notably, short telomere hESCs exhibit
      higher oxidative phosphorylation primed for lineage differentiation, whereas long
      telomere hESCs show elevated glycolysis, another key feature for pluripotency.
      CONCLUSIONS: Telomere length is a marker of the metabolic activity and
      pluripotency state of individual hESCs. Single cell analysis of telomeres and RNA
      sequencing can be exploited to further understand the molecular mechanisms of
      telomere heterogeneity.

PMID- 29216890
TI  - In silico and phylogenetic analyses of partial BbRAP-1, BbCP2, BbSBP-4 and
      BbbetaTUB gene sequences of Babesia bovis isolates from cattle in South Africa.
AB  - BACKGROUND: Bovine babesiosis is one of the most economically important tick
      borne diseases threatening the livestock industry globally including South
      Africa. This disease is induced by members of Babesia bovis species. Antigenic
      variations among geographical strains of B. bovis, and these heterogeneities are
      cited as the mechanism by which parasites evade from host immune system and they
      hamper the successful development of a single vaccine that could confer absolute
      protection. Given the economic importance of livestock industry in South Africa,
      the extent of genetic diversity among field isolates of B. bovis merits extensive
      investigation. In this study, we genetically characterized partial genes of B.
      bovis and studied the phylogenetic relationship among B. bovis isolates of South
      African origin. The genes, which were PCR-amplified from bovine samples collected
      from different locations across South Africa, coded for rhoptry-associated
      protein 1 (BbRAP-1), cysteine peptidase 2 (BbCP2), spherical body protein 4
      (BbSBP-4) and beta-tubulin (BbbetaTUB). Phylogenies were inferred from newly
      determined sequences using the neighbour-joining approach. RESULTS: Nested PCR
      assays with gene-specific primers indicated that, of the 54 bovine samples
      tested, 59.3% (32/54; 95% CI = 46.0-71.3%), 27.8% (15/54; 95% CI = 17.6-40.9%),
      37.0% (20/54; 95% CI = 25.4-50.4%) and 29.6% (16/54; 95% CI = 19.1-42.8%)
      possessed BbRAP-1, BbCP2, BbSBP-4 and BbbetaTUB fragments, respectively.
      Sequencing of PCR-generated fragments revealed that nucleotide sequences of each
      of the four genes were highly conserved among the B. bovis isolates examined.
      Phylogenetic analyses of BbCP2, BbSBP-4 and BbbetaTUB sequences indicated a close
      phylogenetic relatedness among South African-derived sequences and those of
      global B. bovis strains. CONCLUSION: The data reported in this study indicated
      that there is a high conservation among the genes of B. bovis isolates from
      cattle in South Africa. These findings give an indication that immunologically
      important proteins encoded by these genes could potentially be considered for
      exploitation as viable candidates for inclusion in recombinant subunit vaccines.

PMID- 29216889
TI  - Targeting the cross-talk between Urokinase receptor and Formyl peptide receptor
      type 1 to prevent invasion and trans-endothelial migration of melanoma cells.
AB  - BACKGROUND: Accumulating evidence demonstrates that the Urokinase Receptor (uPAR)
      regulates tumor cell migration through its assembly in composite regulatory units
      with transmembrane receptors, and uPAR88-92 is the minimal sequence required to
      induce cell motility through the Formyl Peptide Receptor type 1 (FPR1). Both uPAR
      and FPR1 are involved in melanoma tumor progression, suggesting that they may be
      targeted for therapeutic purposes. In this study, the role of the uPAR-FPR1 cross
      talk to sustain melanoma cell ability to invade extracellular matrix and cross
      endothelial barriers is investigated. Also, the possibility that inhibition of
      the uPAR mediated FPR1-dependent signaling may prevent matrix invasion and
      transendothelial migration of melanoma cells was investigated. METHODS:
      Expression levels of uPAR and FPR1 were assessed by immunocytochemistry, Western
      Blot and qRT-PCR. Cell migration was investigated by Boyden chamber and wound
      healing assays. Migration and invasion kinetics, trans-endothelial migration and
      proliferation of melanoma cells were monitored in real time using the xCELLigence
      technology. The agonist-triggered FPR1 internalization was visualized by confocal
      microscope. Cell adhesion to endothelium was determined by fluorometer
      measurement of cell-associated fluorescence or identified on multiple z-series by
      laser confocal microscopy. The 3D-organotypic models were set up by seeding
      melanoma cells onto collagen I matrices embedded dermal fibroblasts. Data were
      analyzed by one-way ANOVA and post-hoc Dunnett t-test for multiple comparisons.
      RESULTS: We found that the co-expression of uPAR and FPR1 confers to A375 and M14
      melanoma cells a clear-cut capability to move towards chemotactic gradients, to
      cross extracellular matrix and endothelial monolayers. FPR1 activity is required,
      as cell migration and invasion were abrogated by receptor desensitization.
      Finally, melanoma cell ability to move toward chemotactic gradients, invade
      matrigel or fibroblast-embedded collagen matrices and cross endothelial
      monolayers are prevented by anti-uPAR84-95 antibodies or by the RI-3 peptide
      which we have previously shown to inhibit the uPAR84-95/FPR1 interaction.
      CONCLUSIONS: Collectively, our findings identify uPAR and FPR1 as relevant
      effectors of melanoma cell invasiveness and suggest that inhibitors of the uPAR84
      95/FPR1 cross-talk may be useful for the treatment of metastatic melanoma.

PMID- 29216891
TI  - A multi-trait systems approach reveals a response cascade to bleaching in corals.
AB  - BACKGROUND: Climate change causes the breakdown of the symbiotic relationships
      between reef-building corals and their photosynthetic symbionts (genus
      Symbiodinium), with thermal anomalies in 2015-2016 triggering the most widespread
      mass coral bleaching on record and unprecedented mortality on the Great Barrier
      Reef. Targeted studies using specific coral stress indicators have highlighted
      the complexity of the physiological processes occurring during thermal stress,
      but have been unable to provide a clear mechanistic understanding of coral
      bleaching. RESULTS: Here, we present an extensive multi-trait-based study in
      which we compare the thermal stress responses of two phylogenetically distinct
      and widely distributed coral species, Acropora millepora and Stylophora
      pistillata, integrating 14 individual stress indicators over time across a
      simulated thermal anomaly. We found that key stress responses were conserved
      across both taxa, with the loss of symbionts and the activation of antioxidant
      mechanisms occurring well before collapse of the physiological parameters,
      including gross oxygen production and chlorophyll a. Our study also revealed
      species-specific traits, including differences in the timing of antioxidant
      regulation, as well as drastic differences in the production of the sulfur
      compound dimethylsulfoniopropionate during bleaching. Indeed, the concentration
      of this antioxidant increased two-fold in A. millepora after the corals started
      to bleach, while it decreased 70% in S. pistillata. CONCLUSIONS: We identify a
      well-defined cascading response to thermal stress, demarking clear
      pathophysiological reactions conserved across the two species, which might be
      central to fully understanding the mechanisms triggering thermally induced coral
      bleaching. These results highlight that bleaching is a conserved mechanism, but
      specific adaptations linked to the coral's antioxidant capacity drive differences
      in the sensitivity and thus tolerance of each coral species to thermal stress.

PMID- 29216892
TI  - Opiate agonist treatment to improve health of individuals with opioid use
      disorder in Lebanon.
AB  - BACKGROUND: Opioid agonist therapy has been widely used to reduce harms among
      individuals with opioid use disorder but its effectiveness has not been evaluated
      in the Middle East North African (MENA) region. This study aims to evaluate the
      effectiveness of a program using opioid agonist therapy in combination with
      psychosocial support on improving psychological and social well-being, reducing
      arrest, and reducing risky behavior in individuals with opioid use disorder in
      Lebanon. METHODS: A one-group pre-test post-test design study was performed at
      SKOUN Lebanese Addiction Centre between January 2013 and December 2014. Eighty
      six out of 181 patients agreed to participate and completed the 3-month
      assessment and 38 concluded the 12-month assessment. Psychological (depression
      and anxiety, quality of life), substance dependence/abuse, behavioral (injecting
      behavior, sharing needles and paraphernalia), and social outcomes were evaluated
      at baseline, 3, and 12 months post-treatment. RESULTS: Remarkable statistical
      significance improvements were observed 3 months after treatment in most outcome
      variables including quality of life, anxiety, substance dependence, overdose,
      employment, and injecting behavior. Improvements were sustained 12 months after
      treatment. CONCLUSION: Results support expanding the access to opioid agonist
      therapy in other MENA countries to treat substance dependence and reduce harms
      among individuals with opioid use disorder.

PMID- 29216894
TI  - Early winners and losers in dialysis center pay-for-performance.
AB  - BACKGROUND: We examined the association of dialysis facility characteristics with
      payment reductions and change in clinical performance measures during the first
      year of the United States Centers for Medicare & Medicaid Services (CMS) End
      Stage Renal Disease Quality Incentive Plan (ESRD QIP) to determine its potential
      impact on quality and disparities in dialysis care. METHODS: We linked the 2012
      ESRD QIP Facility Performance File to the 2007-2011 American Community Survey by
      zip code and dichotomized the QIP total performance scores-derived from percent
      of patients with urea reduction rate > 65, hemoglobin < 10 g/dL, and hemoglobin >
      12 g/dL-as 'any' versus 'no' payment reduction. We characterized associations
      between payment reduction and dialysis facility characteristics and neighborhood
      demographics, and examined changes in facility outcomes between 2007 and 2010.
      RESULTS: In multivariable analysis, facilities with any payment reduction were
      more likely to have longer operation (OR 1.03 per year), a medium or large number
      of stations (OR 1.31 and OR 1.42, respectively), and a larger proportion of
      African Americans (OR 1.25, highest versus lowest quartile), all p < 0.05. Most
      improvement in clinical performance was due to reduced overtreatment of anemia, a
      decline in the percentage of patients with hemoglobin >= 12 g/dL; for-profits and
      facilities in African American neighborhoods had the greatest reduction.
      CONCLUSIONS: In the first year of CMS pay-for-performance, most clinical
      improvement was due to reduced overtreatment of anemia. Facilities in African
      American neighborhoods were more likely to receive a payment reduction, despite
      their large decline in anemia overtreatment.

PMID- 29216893
TI  - The integration of chloroplast protein targeting with plant developmental and
      stress responses.
AB  - The plastids, including chloroplasts, are a group of interrelated organelles that
      confer photoautotrophic growth and the unique metabolic capabilities that are
      characteristic of plant systems. Plastid biogenesis relies on the expression,
      import, and assembly of thousands of nuclear encoded preproteins. Plastid
      proteomes undergo rapid remodeling in response to developmental and environmental
      signals to generate functionally distinct plastid types in specific cells and
      tissues. In this review, we will highlight the central role of the plastid
      protein import system in regulating and coordinating the import of functionally
      related sets of preproteins that are required for plastid-type transitions and
      maintenance.

PMID- 29216895
TI  - 'We do not know': a qualitative study exploring boys perceptions of menstruation
      in India.
AB  - BACKGROUND: In low-middle income countries and other areas of poverty, menstrual
      hygiene management (MHM) can be problematic for women and girls. Issues include
      lack of knowledge about menstruation and MHM, and stigma around menstruation,
      also access to affordable and absorbent materials; privacy to change; adequate
      washing, cleaning and drying facilities; as well as appropriate and accessible
      disposal facilities. In order to effect change and tackle these issues,
      particularly in patriarchal societies, males may need to become advocates for MHM
      alongside women. However, little is known about their knowledge and attitudes
      towards menstruation, which may need addressing before they can assist in acting
      as advocates for change. The present study was undertaken to explore knowledge
      and attitudes about menstruation among adolescent boys across India, in order to
      gauge their potential to support their 'sisters'. METHODS: The study was
      undertaken across three states in India, chosen a priori to represent the
      cultural and socio-economic diversity. Qualitative data using focus group
      discussions with 85 boys aged 13-17 years, from 8 schools, was gathered. Data
      were analysed using thematic analysis. RESULTS: The results were organised into
      three main themes, reflecting the key research questions: boys' knowledge of
      menstruation, source of knowledge, and attitudes towards menstruation and
      menstruating girls. Knowledge comprised three aspects; biological function which
      were generally poorly understood; cultural rites which were recognized by all;
      and girls' behaviour and demeanour, which were noted to be withdrawn. Some boys
      learnt about puberty and menstruation as part of the curriculum but had concerns
      this was not in-depth, or was missed out altogether. Most gathered knowledge from
      informal sources, from overhearing conversations or observing cultural rituals.
      Few boys openly displayed a negative attitude, although a minority voiced the
      idea that menstruation is a 'disease'. Boys were mostly sympathetic to their
      menstruating sisters and wanted to support them. CONCLUSIONS: These findings
      provide some optimism that males can become advocates in moving forward the MHM
      agenda. The reasons for this are twofold: boys were keen for knowledge about
      menstruation, searching information out despite societal norms being for them to
      remain ignorant, they were also largely sympathetic to their menstruating sisters
      and fellow classmates and understanding of the issues surrounding the need for
      good MHM.

PMID- 29216896
TI  - What will it take? Pathways, time and funding: Australian medical students'
      perspective on clinician-scientist training.
AB  - BACKGROUND: Clinician-scientists are in decline worldwide. They represent a
      unique niche in medicine by bridging the gap between scientific discovery and
      patient care. A national, integrated approach to training clinician-scientists,
      typically programs that comprise a comprehensive MD-PhD pathway, are customary.
      Such a pathway is lacking in Australia. The objective was to gather perceptions
      from Australian medical students on factors they perceive would influence their
      decision to pursue clinician-scientist training. METHODS: A cross-sectional mixed
      methods design used quantitative and qualitative questions in an online self
      report survey with medical students from a four-year MD program. Quantitative
      measures comprised scaled response questions regarding prior experience and
      current involvement in research, and short- and long-term opinions about factors
      that influence their decisions to undertake a research higher degree (RHD) during
      medical school. Qualitative questions gathered broader perceptions of what a
      career pathway as a clinician-scientist would include and what factors are most
      conducive to a medical student's commitment to MD-PhD training. RESULTS:
      Respondents (N = 418; 51% female) indicated Time, Funding and Pathway as the
      major themes arising from the qualitative data, highlighting negative perceptions
      rather than possible benefits to RHD training. The lack of an evident Pathway was
      inter-related to Time and Funding. Themes were supported by the quantitative
      data. Sixty percent of students have previous research experience of varying
      forms, and 90% report a current interest, mainly to improve their career
      prospects. CONCLUSIONS: The data emphasise the need for an MD-PhD pathway in
      Australia. A model that provides an early, integrated, and exclusive approach to
      research training pathways across all stages of medical education is suggested as
      the best way to rejuvenate the clinician-scientist. A national pathway that
      addresses factors influencing career decision making throughout the medical
      education continuum should include an appropriate funding structure, and provide
      early and continuing advice and mentoring. It should be flexible, gender
      equitable, and include post-graduate training. The implications of implementing
      MD-PhD programs represent a substantial investment. However this should not be a
      deterrent to Australia's commitment to an MD-PhD pathway, but rather a challenge
      to help ensure our future healthcare is guided by highly trained and competent
      clinician-scientists.

PMID- 29216897
TI  - Measuring self-rated health status among resettled adult refugee populations to
      inform practice and policy - a scoping review.
AB  - BACKGROUND: The health status of refugees is a significant factor in determining
      their success in resettlement and relies heavily on self-rated measures of
      refugee health. The selection of robust and appropriate self-rated health
      measurement tools is challenging due to the number and methodological variation
      in the use of assessment tools across refugee health studies. This study
      describes the existing self-report health measures which have been used in
      studies of adult refugees living in the community to allow us to address the
      challenges of selecting appropriate assessments to measure health within refugee
      groups. METHODS: Electronic databases of Ovid Medline, CINAHL, SCOPUS, Embase and
      Scopus. RESULTS: This review identified 45 different self-rated health
      measurements in 183 studies. Most of the studies were cross sectional
      explorations of the mental health status of refugees living in community settings
      within Western nations. A third of the tools were designed specifically for use
      within refugee populations. More than half of the identified measurement tools
      have been evaluated for reliability and/or validity within refugee populations.
      Much variation was found in the selection, development and testing of measurement
      tools across the reviewed studies. CONCLUSION: This review shows that there are
      currently a number of reliable and valid tools available for use in refugee
      health research; however, further work is required to achieve consistency in the
      quality and in the use of these tools. Methodological guidelines are required to
      assist researchers and clinicians in the development and testing of self-rated
      health measurement tools for use in refugee research.

PMID- 29216898
TI  - Is the relationship between increased knee muscle strength and improved physical
      function following exercise dependent on baseline physical function status?
AB  - BACKGROUND: Clinical guidelines recommend knee muscle strengthening exercises to
      improve physical function. However, the amount of knee muscle strength increase
      needed for clinically relevant improvements in physical function is unclear.
      Understanding how much increase in knee muscle strength is associated with
      improved physical function could assist clinicians in providing appropriate
      strength gain targets for their patients in order to optimise outcomes from
      exercise. The aim of this study was to investigate whether an increase in knee
      muscle strength is associated with improved self-reported physical function
      following exercise; and whether the relationship differs according to physical
      function status at baseline. METHODS: Data from 100 participants with medial knee
      osteoarthritis enrolled in a 12-week randomised controlled trial comparing
      neuromuscular exercise to quadriceps strengthening exercise were pooled.
      Participants were categorised as having mild, moderate or severe physical
      dysfunction at baseline using the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical
      function (dependent variable) and peak isometric knee extensor and flexor
      strength (independent variables) were evaluated with and without accounting for
      baseline physical function status and covariates using linear regression models.
      RESULTS: In covariate-adjusted models without accounting for baseline physical
      function, every 1-unit (Nm/kg) increase in knee extensor strength was associated
      with physical function improvement of 17 WOMAC units (95% confidence interval
      (CI) -29 to -5). When accounting for baseline severity of physical function,
      every 1-unit increase in knee extensor strength was associated with physical
      function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with
      severe physical dysfunction. There were no associations between change in
      strength and change in physical function in participants with mild or moderate
      physical dysfunction at baseline. The association between change in knee flexor
      strength and change in physical function was not significant, irrespective of
      baseline function status. CONCLUSIONS: In patients with severe physical
      dysfunction, an increase in knee extensor strength and improved physical function
      were associated. TRIAL REGISTRATION: ANZCTR 12610000660088 . Registered 12 August
      2010.

PMID- 29216899
TI  - Generic-reference and generic-generic bioequivalence of forty-two, randomly
      selected, on-market generic products of fourteen immediate-release oral drugs.
AB  - BACKGROUND: The extents of generic-reference and generic-generic average
      bioequivalence and intra-subject variation of on-market drug products have not
      been prospectively studied on a large scale. METHODS: We assessed bioequivalence
      of 42 generic products of 14 immediate-release oral drugs with the highest number
      of generic products on the Saudi market. We conducted 14 four-sequence,
      randomized, crossover studies on the reference and three randomly-selected
      generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin,
      clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole,
      paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum
      concentration (Cmax) and area-under-the-concentration-time-curve, to last
      measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to
      Cmax time of reference product (AUCReftmax) were calculated using non
      compartmental method and their 90% confidence intervals (CI) were compared to the
      80.00%-125.00% bioequivalence range. Percentages of individual ratios falling
      outside the +/-25% range were also determined. RESULTS: Mean (SD) age and body
      mass-index of 700 healthy volunteers (28-80/study) were 32.2 (6.2) years and 24.4
      (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and
      AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show
      bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed
      bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and
      21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic
      comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and
      66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence.
      Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs
      failed to show bioequivalence. Average geometric mean ratio deviation from 100%
      was <=3.2 and <=5.4 percentage points for AUCI and Cmax, respectively, in both
      generic-reference and generic-generic comparisons. Individual generic/reference
      and generic/generic ratios, respectively, were within the +/-25% range in >75% of
      individuals in 79% and 71% of the 14 drugs for AUCT and 36% and 29% for Cmax.
      CONCLUSIONS: On-market generic drug products continue to be reference
      bioequivalent and are bioequivalent to each other based on AUCT, AUCI, and Cmax
      but not AUCReftmax. Average deviation of geometric mean ratios and intra-subject
      variations are similar between reference-generic and generic-generic comparisons.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01344070 (registered April
      3, 2011).

PMID- 29216900
TI  - Treatment with a DNA methyltransferase inhibitor feminizes zebrafish and induces
      long-term expression changes in the gonads.
AB  - BACKGROUND: The role of epigenetic modifications such as DNA methylation during
      vertebrate sexual development is far from being clear. Using the zebrafish model,
      we tested the effects of one of the most common DNA methyltransferase (dnmt)
      inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment
      of acute myeloid leukaemia and is under active investigation for the treatment of
      solid tumours. Several dose-response experiments were carried out during two
      periods, including not only the very first days of development (0-6 days post
      fertilization, dpf), as done in previous studies, but also, and as a novelty, the
      period of gonadal development (10-30 dpf). RESULTS: Early treatment with 5-aza-dC
      altered embryonic development, delayed hatching and increased teratology and
      mortality, as expected. The most striking result, however, was an increase in the
      number of females, suggesting that alterations induced by 5-aza-dC treatment can
      affect sexual development as well. Results were confirmed when treatment
      coincided with gonadal development. In addition, we also found that the adult
      gonadal transcriptome of 5-aza-dC-exposed females included significant changes in
      the expression of key reproduction-related genes (e.g. cyp11a1, esr2b and figla),
      and that several pro-female-related pathways such as the Fanconi anaemia or the
      Wnt signalling pathways were downregulated. Furthermore, an overall inhibition of
      genes implicated in epigenetic regulatory mechanisms (e.g. dnmt1, dicer, cbx4)
      was also observed. CONCLUSIONS: Taken together, our results indicate that
      treatment with a DNA methylation inhibitor can also alter the sexual development
      in zebrafish, with permanent alterations of the adult gonadal transcriptome, at
      least in females. Our results show the importance of DNA methylation for proper
      control of sexual development, open new avenues for the potential control of sex
      ratios in fish (aquaculture, population control) and call attention to possibly
      hidden long-term effects of dnmt therapy when used, for example, in the treatment
      of prepuberal children affected by some types of cancer.

PMID- 29216903
TI  - Evaluation of clinical practice guidelines using the AGREE instrument: comparison
      between data obtained from AGREE I and AGREE II.
AB  - OBJECTIVE: The Appraisal of Guidelines for Research and Evaluation (AGREE) is a
      representative, quantitative evaluation tool for evidence-based clinical practice
      guidelines (CPGs). Recently, AGREE was revised (AGREE II). The continuity of
      evaluation data obtained from the original version (AGREE I) has not yet been
      demonstrated. The present study investigated the relationship between data
      obtained from AGREE I and AGREE II to evaluate the continuity between the two
      measurement tools. RESULTS: An evaluation team consisting of three trained
      librarians evaluated 68 CPGs issued in 2011-2012 in Japan using AGREE I and AGREE
      II. The correlation coefficients for the six domains were: (1) scope and purpose
      0.758; (2) stakeholder involvement 0.708; (3) rigor of development 0.982; (4)
      clarity of presentation 0.702; (5) applicability 0.919; and (6) editorial
      independence 0.971. The item "Overall Guideline Assessment" was newly introduced
      in AGREE II. This global item had a correlation coefficient of 0.628 using the
      six AGREE I domains, and 0.685 using the 23 items. Our results suggest that data
      obtained from AGREE I can be transferred to AGREE II, and the "Overall Guideline
      Assessment" data can be determined with high reliability using a standardized
      score of the 23 items.

PMID- 29216901
TI  - Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral
      sclerosis in Greek patients.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose
      complex pathology has been associated with a strong genetic component in the
      context of both familial and sporadic disease. Herein, we adopted a next
      generation sequencing approach to Greek patients suffering from sporadic ALS
      (together with their healthy counterparts) in order to explore further the
      genetic basis of sporadic ALS (sALS). RESULTS: Whole-genome sequencing analysis
      of Greek sALS patients revealed a positive association between FTO and TBC1D1
      gene variants and sALS. Further, linkage disequilibrium analyses were suggestive
      of a specific disease-associated haplotype for FTO gene variants. Genotyping for
      these variants was performed in Greek, Sardinian, and Turkish sALS patients. A
      lack of association between FTO and TBC1D1 variants and sALS in patients of
      Sardinian and Turkish descent may suggest a founder effect in the Greek
      population. FTO was found to be highly expressed in motor neurons, while in
      silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the
      genomic variants in question. CONCLUSIONS: To our knowledge, this is the first
      study to present a possible association between FTO gene variants and the genetic
      etiology of sALS. In addition, the next-generation sequencing-based genomics
      approach coupled with the two-step validation strategy described herein has the
      potential to be applied to other types of human complex genetic disorders in
      order to identify variants of clinical significance.

PMID- 29216902
TI  - Improved drug safety through intensive pharmacovigilance in hospitalized
      pediatric patients.
AB  - BACKGROUND: The aim of this study was to detect and analyze Adverse Drug
      Reactions (ADRs) through Intensive Pharmacovigilance (IPV) in hospitalized
      pediatric patients to improve drug safety. METHODS: A prospective 6-month cross
      sectional study was performed in the pediatric service of a regional hospital in
      Mexico in order to assess hospitalized children from 1 day to 18 years old. The
      inclusion criteria were: both genders, all hospitalization causes, and at least
      one prescribed medication (indistinct drug group). Notifications were performed
      through medical visits, phone calls, or spontaneous reports. ADR suspicions were
      assessed with severity scales: Naranjo algorithm, Schumock & Thornton and Hartwig
      and Siegel. RESULTS: From a total of 1083 hospital admissions, 19 ADRs were
      recorded. The average age of patients in years was 7.2 (+/-5.9). The causality
      assessment in this study showed that most of the ADRs were probable (68.4%) and 4
      certain (8.2%); causality was mainly attributed to antibiotics (AB) and an
      antiepileptic drug. We found a relationship of AB with ADRs (p < 0.05) with an
      increased risk at the third day of prescription (p < 0.05). The average severity
      was level 2 and 21% were classified as "preventable". Lastly, an increase in
      hospital stay associated with ADRs (p < 0.05) and with concomitant medications (p
      < 0.05), was also found. The most severe ADRs were hemolysis and toxic epidermal
      necrolysis. CONCLUSIONS: IPV was an effective tool for ADR prevention, detection,
      and treatment in hospitalized patients. The intensive monitoring approach in
      pharmacovigilance amplifies ADR detection and this translates into the
      improvement of drug safety in children.

PMID- 29216904
TI  - Technology for fostering intergenerational connectivity: scoping review protocol.
AB  - BACKGROUND: The simultaneous increase in geographically dispersed families and
      general decrease in engagement in local communities is resulting in fewer
      opportunities for youth and older adults interact in meaningful ways. Technology
      is becoming increasingly pervasive and flexible and providing new opportunities
      to foster intergenerational connection that can be implemented and evaluated
      across a multitude of populations and contexts. What research has been done in
      this area is spread across disciplines and what aspects of technologies could
      make them more effective is not well understood. METHOD: The scoping review will
      be completed in five stages: (1) identifying the research question, (2)
      identifying relevant studies, (3) selecting studies, (4) charting the data, and
      (5) collating, summarizing, and reporting the results. Comprehensive descriptive
      data from each study will be presented along with an analysis of similarities and
      differences in research from different disciplines. DISCUSSION: This scoping
      review focuses on a search of the literature to gain an understanding of what
      technologies have been used specifically for fostering intergenerational
      connectivity and to establish what future directions for research could be. To
      the authors' knowledge, it is the first scoping review of its kind.

PMID- 29216905
TI  - Variations in visceral leishmaniasis burden, mortality and the pathway to care
      within Bihar, India.
AB  - BACKGROUND: Visceral leishmaniasis (VL) has been targeted by the WHO for
      elimination as a public health problem (< 1 case/10,000 people/year) in the
      Indian sub-continent (ISC) by 2020. Bihar State in India, which accounts for the
      majority of cases in the ISC, remains a major target for this elimination effort.
      However, there is considerable spatial, temporal and sub-population variation in
      occurrence of the disease and the pathway to care, which is largely unexplored
      and a threat to achieving the target. METHODS: Data from 6081 suspected VL
      patients who reported being clinically diagnosed during 2012-2013 across eight
      districts in Bihar were analysed. Graphical comparisons and Chi-square tests were
      used to determine differences in the burden of identified cases by season,
      district, age and sex. Log-linear regression models were fitted to onset (of
      symptoms)-to-diagnosis and onset-to-treatment waiting times to estimate their
      associations with age, sex, district and various socio-economic factors (SEFs).
      Logistic regression models were used to identify factors associated with
      mortality. RESULTS: Comparisons of VL caseloads suggested an annual cycle peaking
      in January-March. A 17-fold variation in the burden of identified cases across
      districts and under-representation of young children (0-5 years) relative to age
      specific populations in Bihar were observed. Women accounted for a significantly
      lower proportion of the reported cases than men (41 vs 59%, P < 0.0001). Age,
      district of residence, house wall materials, caste, treatment cost, travelling
      for diagnosis and the number of treatments for symptoms before diagnosis were
      identified as correlates of waiting times. Mortality was associated with age,
      district of residence, onset-to-treatment waiting time, treatment duration,
      cattle ownership and cost of diagnosis. CONCLUSIONS: The distribution of VL in
      Bihar is highly heterogeneous, and reported caseloads and associated mortality
      vary significantly across different districts, posing different challenges to the
      elimination campaign. Socio-economic factors are important correlates of these
      differences, suggesting that elimination will require tailoring to population and
      sub-population circumstances.

PMID- 29216906
TI  - Detection of metallo-beta-lactamases-encoding genes among clinical isolates of
      Pseudomonas aeruginosa in a tertiary care hospital, Kathmandu, Nepal.
AB  - OBJECTIVES: This study was carried out to determine the prevalence of metallo
      beta-lactamases (MBLs) producing Pseudomonas aeruginosa in imipenem
      nonsusceptible isolates and to detect MBL-encoding genes among MBLs-positive
      isolates. RESULTS: Metallo-beta-lactamases production was detected in 68.6%
      isolates of P. aeruginosa with reduced susceptibility to imipenem. The bla VIM-2
      gene was detected in 75% isolates and bla IMP-1 was detected in 25% isolates. All
      MBLs-positive isolates were multidrug resistant with a high level of resistance
      to imipenem (MIC 16 to >= 32 ug/ml), meropenem (MIC 16 to >= 32 ug/ml), and
      ceftazidime (MIC 64 to >= 512 ug/ml). All MBL-positive isolates were susceptible
      (MIC <= 2 ug/ml) to colistin. We found high prevalence of MBL-producing P.
      aeruginosa. To our knowledge this is the first report of detection of bla VIM-2
      and bla IMP-1 in P. aeruginosa from Nepal. This indicates the need for awareness
      to prevent the spreading of these resistant isolates in hospital setting.

PMID- 29216907
TI  - Angiogenesis and VEGF-expressing cells are identified predominantly in the fascia
      rather than in the muscle during the early phase of dermatomyositis.
AB  - BACKGROUND: We previously demonstrated that fasciitis is a common lesion in
      dermatomyositis (DM) and that DM-associated fasciitis is detectable, as the
      result of the increased vascularity in the fascia, by power Doppler
      ultrasonography. We aimed to investigate whether angiogenesis and vascular
      endothelial growth factor (VEGF)-expressing cells in the fascia are
      histologically demonstrated during the early phase of DM, and whether
      inflammation is involved in angiogenesis and an increased number of VEGF
      expressing cells. METHODS: We prospectively evaluated 22 patients with DM and 11
      patients with polymyositis (PM). Immunohistochemical staining for CD31, VEGF, and
      tumor necrosis factor-alpha (TNF-alpha) were performed on paraffin-embedded
      sections. The total vascular inflammation score (TVIS), angiogenesis score (AS),
      and numbers of VEGF-expressing and TNF-alpha-expressing cells were analyzed in
      the fascia and muscle. RESULTS: Significant fasciitis was detected in most of the
      patients DM with or without myositis-specific/associated antibodies, while mild
      fasciitis was detected in four patients with PM, two of whom were positive for
      anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies. The AS and the number of
      VEGF-expressing cells in the fascia of patients with DM were significantly
      greater than those of patients with PM; no significant difference was observed in
      muscle in patients with DM and PM. The number of VEGF-expressing cells in the
      fascia correlated with the AS of DM patients. In early-phase DM, the AS, the
      number of VEGF-expressing cells, and the TVIS in the fascia were significantly
      higher than in muscle. However, no significant differences were observed in these
      scores excluding the TVIS between muscle and the fascia in late-phase DM. In DM
      patients, the TVIS correlated with the AS in the fascia, while the number of TNF
      alpha-expressing cells correlated with the TVIS and the number of VEGF-expressing
      cells in the fascia. CONCLUSION: Angiogenesis, the number of VEGF-expressing
      cells, and the degree of inflammation were higher in the fascia in DM than in PM,
      and were increased predominantly in the fascia rather than in the muscle in early
      phase DM. The degree of inflammation correlated with that of angiogenesis in the
      fascia of DM. The fascia can therefore be a primary site of inflammation and
      angiogenesis in the pathogenesis of DM.

PMID- 29216908
TI  - Clinical and neuropathological features of ALS/FTD with TIA1 mutations.
AB  - Mutations in the stress granule protein T-cell restricted intracellular antigen 1
      (TIA1) were recently shown to cause amyotrophic lateral sclerosis (ALS) with or
      without frontotemporal dementia (FTD). Here, we provide detailed clinical and
      neuropathological descriptions of nine cases with TIA1 mutations, together with
      comparisons to sporadic ALS (sALS) and ALS due to repeat expansions in C9orf72
      (C9orf72+). All nine patients with confirmed mutations in TIA1 were female. The
      clinical phenotype was heterogeneous with a range in the age at onset from late
      twenties to the eighth decade (mean = 60 years) and disease duration from one to
      6 years (mean = 3 years). Initial presentation was either focal weakness or
      language impairment. All affected individuals received a final diagnosis of ALS
      with or without FTD. No psychosis or parkinsonism was described.
      Neuropathological examination on five patients found typical features of ALS and
      frontotemporal lobar degeneration (FTLD-TDP, type B) with anatomically widespread
      TDP-43 proteinopathy. In contrast to C9orf72+ cases, caudate atrophy and
      hippocampal sclerosis were not prominent. Detailed evaluation of the pyramidal
      motor system found a similar degree of neurodegeneration and TDP-43 pathology as
      in sALS and C9orf72+ cases; however, cases with TIA1 mutations had increased
      numbers of lower motor neurons containing round eosinophilic and Lewy body-like
      inclusions on HE stain and round compact cytoplasmic inclusions with TDP-43
      immunohistochemistry. Immunohistochemistry and immunofluorescence failed to
      demonstrate any labeling of inclusions with antibodies against TIA1. In summary,
      our TIA1 mutation carriers developed ALS with or without FTD, with a wide range
      in age at onset, but without other neurological or psychiatric features. The
      neuropathology was characterized by widespread TDP-43 pathology, but a more
      restricted pattern of neurodegeneration than C9orf72+ cases. Increased numbers of
      round eosinophilic and Lewy-body like inclusions in lower motor neurons may be a
      distinctive feature of ALS caused by TIA1 mutations.

PMID- 29216909
TI  - Which measuring site in ankylosing spondylitis is best to detect bone loss and
      what predicts the decline: results from a 5-year prospective study.
AB  - BACKGROUND: Studies have shown increased prevalence of osteoporosis and increased
      risk for vertebral fractures in patients with ankylosing spondylitis (AS).
      Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior
      (AP) projection may be difficult to interpret due to the ligamentous
      calcifications, and the lateral projection might be a better measuring site. Our
      objectives were to investigate BMD changes after 5 years at different measuring
      sites in patients with AS and to evaluate disease-related variables and
      medications as predictors for BMD changes. METHODS: In a longitudinal study, BMD
      in Swedish AS patients, 50 +/- 13 years old, was measured with dual-energy x-ray
      absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and
      the total radius at baseline and after 5 years. Patients were assessed with
      questionnaires, blood samples, and spinal radiographs for grading of AS-related
      alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal
      Score (mSASSS) and assessment of vertebral fractures by the Genant score.
      Multiple linear regression analyses were used to investigate predictors for BMD
      changes. RESULTS: Of 204 patients included at baseline, 168 (82%) were re
      examined after 5 years (92 men and 76 women). BMD decreased significantly at the
      femoral neck and radius and increased significantly at the lumbar spine, both for
      AP and lateral projections. Mean C-reactive protein during follow-up predicted a
      decrease in the femoral neck BMD (change in %, beta = -0.15, p = 0.046). Use of
      bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to
      0.013), except for the total radius. Use of tumor necrosis factor inhibitors
      (TNFi) predicted an increase in AP spinal BMD (beta = 3.15, p = 0.012).
      CONCLUSION: The current study (which has a long follow-up, many measuring sites,
      and is the first to longitudinally assess the lateral projection of the spine in
      AS patients) surprisingly showed that lateral projection spinal BMD increased.
      This study suggests that the best site to assess bone loss in AS patients is the
      femoral neck and that inflammation has an adverse effect, and the use of
      bisphosphonates and TNFi has a positive effect, on BMD in AS patients.

PMID- 29216910
TI  - Perceived causes of stress among a group of western Canadian dental students.
AB  - OBJECTIVE: The demanding nature of dental education, both academically and
      clinically, results in higher levels of perceived stress among its students. The
      aim of this study was to determine how dental students at the College of
      Dentistry, University of Saskatchewan perceived stress. During the 2013-2014
      academic year, all students were asked to complete a modified dental
      environmental survey (DES). RESULTS: Of the 111 students enrolled at the College
      that year 92 completed the survey (response rate = 83%). In general, female
      students reported higher stress levels than males. Higher stress levels were
      associated with living away from home, concerns about manual dexterity and the
      transition from pre-clinical to clinical studies. Additionally, students who
      enter dental school with higher debt loads (> 100,000) report high stress levels
      relating to finances. This study found that financial and clinical workloads
      result in high stress levels among dental students.

PMID- 29216911
TI  - Dynamic expression of cytokine and transcription factor genes during experimental
      Fasciola gigantica infection in buffaloes.
AB  - BACKGROUND: Determining the mechanisms involved in the immune-pathogenesis of the
      tropical liver fluke, Fasciola gigantica, is crucial to the development of any
      effective therapeutic intervention. Here, we examined the differential gene
      expression of cytokines and transcription factors in the liver of F. gigantica
      infected buffaloes, over the course of infection. METHODS: Water buffaloes (swamp
      type) were infected orally with 500 F. gigantica encysted metacercariae. Liver
      tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi).
      Levels of gene expression of nine cytokines (IFN-gamma, TGF-beta, IL-1beta, IL-4,
      IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet,
      GATA-3, Foxp3 and ROR-gammatau) were determined using quantitative real-time PCR
      (qRT-PCR). We evaluated any correlation between gene expression of these immune
      regulatory factors and the severity of liver pathology. RESULTS:
      Histopathological examination revealed that cellular infiltration, hemorrhage and
      fibrosis without calcification in the liver parenchyma of infected buffaloes,
      increased over the course of infection. This progressive pathology was attributed
      to dysregulated and excessive inflammatory responses induced by infection. The
      early infection phase (3-10 dpi) was marked by a generalized immunosuppression
      and elevated TGF-beta expression in order to facilitate parasite colonization. A
      mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite
      survival while minimizing host tissue damage. During late infection (98 dpi), the
      response was biased towards Th1/Treg in order to inhibit the host's Th2
      protective response and promote chronic infection. Both IL-10 and IL-17A and the
      Th17/Treg balance, played key roles in mediating the inflammatory and
      immunoregulatory mechanisms in the liver during chronic fasciolosis. CONCLUSIONS:
      Our data showed distinct CD4+ T helper (Th) polarization and cytokine
      dysregulation in response to F. gigantica infection in water buffaloes over the
      course of infection. Characterizing the temporal expression profiles for host
      immune genes during infection should provide important information for defining
      how F. gigantica adapts and survives in the liver of buffaloes and how host
      immune responses influence F. gigantica pathogenicity.

PMID- 29216912
TI  - Changes in salivary oxytocin after inhalation of clary sage essential oil scent
      in term-pregnant women: a feasibility pilot study.
AB  - OBJECTIVES: This pilot study using a quasi-experimental design was conducted to
      evaluate the feasibility (i.e., limited efficacy, practicality, and
      acceptability) of our intervention protocol involving inhalation of the scent of
      clary sage essential oil by pregnant women and measurement of their preinhalation
      and postinhalation oxytocin levels. RESULTS: Participants were women of singleton
      pregnancies between 38 and 40 gestation weeks (N = 11). The experiment group (n =
      5) inhaled the scent of clary sage essential oil diluted 50-fold with 10 mL of
      odorless propylene glycol for 20 min. Regarding limited efficacy, the oxytocin
      level 15 min postinhalation increased in 3 women and was unmeasurable in 2. The
      control group (n = 6) inhaled similarly without the 50-fold dilution of clary
      sage essential oil. Their oxytocin level increased in 2 women, decreased in 2,
      and was unmeasurable in 2. Uterine contraction was not observed in both groups.
      Regarding practicality, 3 of the 11 women could not collect sufficient saliva.
      The cortisol level decreased in both groups postinhalation. The protocol had no
      negative effects. Regarding acceptability, burden of the protocol was not
      observed. Trial registration The Clinical Trials Registry of University Hospital
      Medical Information Network in Japan-UMIN000017830. Registered:  June 8, 2015.

PMID- 29216913
TI  - Food borne illness amongst health care workers, at a Central Hospital, Harare,
      Zimbabwe, 2016: a retrospective cohort study.
AB  - OBJECTIVES: Health care workers (HCW) at a Central Hospital, were served lunch at
      the hospital canteen on 12 December 2016. On 12 December 2016 at 1700 h, there
      was a sudden onset of symptoms suggestive of gastrointestinal illness among HCW.
      We conducted a retrospective cohort study to determine the cause and the factors
      associated with illness among the HCW at the hospital. RESULTS: We interviewed 96
      respondents. The median incubation period was 6 h (Q1 = 4; Q3 = 12). Abdominal
      pain (97.5%) and watery diarrhoea (95%) were the most common symptoms. The
      majority (97.5%) took antibiotics before collection of stool specimen for
      analysis, with 24 (60%) of 40 HCW treating themselves. Eating chicken (RR = 44.2,
      CI 74.07; 95.34) during lunch was associated with the illness. Staphylococcus
      aureus and Escherichia coli were isolated from food handlers' hands, kitchen
      utensils and work surfaces. Staphylococcus aureus was isolated from chicken. None
      of food handlers had valid medical certificates. One out of four food handlers
      was formally trained.

PMID- 29216914
TI  - Rasch analysis of the participation scale (P-scale): usefulness of the P-scale to
      a rehabilitation services network.
AB  - BACKGROUND: A person's participation is acknowledged as an important outcome of
      the rehabilitation process. The Participation Scale (P-Scale) is an instrument
      that was designed to assess the participation of individuals with a health
      condition or disability. The scale was developed in an effort to better describe
      the participation of people living in middle-income and low-income countries. The
      aim of this study was to use Rasch analysis to examine whether the Participation
      Scale is suitable to assess the perceived ability to take part in participation
      situations by patients with diverse levels of function. METHODS: The sample was
      comprised by 302 patients from a public rehabilitation services network.
      Participants had orthopaedic or neurological health conditions, were at least 18
      years old, and completed the Participation Scale. Rasch analysis was conducted
      using the Winsteps software. RESULTS: The mean age of all participants was 45.5
      years (standard deviation = 14.4), 52% were male, 86% had orthopaedic conditions,
      and 52% had chronic symptoms. Rasch analysis was performed using a dichotomous
      rating scale, and only one item showed misfit. Dimensionality analysis supported
      the existence of only one Rasch dimension. The person separation index was 1.51,
      and the item separation index was 6.38. Items N2 and N14 showed Differential Item
      Functioning between men and women. Items N6 and N12 showed Differential Item
      Functioning between acute and chronic conditions. The item difficulty range was 
      1.78 to 2.09 logits, while the sample ability range was -2.41 to 4.61 logits.
      CONCLUSIONS: The P-Scale was found to be useful as a screening tool for
      participation problems reported by patients in a rehabilitation context, despite
      some issues that should be addressed to further improve the scale.

PMID- 29216915
TI  - Rheumatoid arthritis bone marrow environment supports Th17 response.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic, autoimmune disease leading
      to joint destruction and ultimately disability. Bone marrow (BM) is an important
      compartment in RA, where pathological processes from "outside the joint" can
      occur. IL-17 is a cytokine that exerts proinflammatory effects and participates
      in the process of bone destruction. It is believed that IL-17 is involved in
      pathogenesis of RA. However, little is known about the biology of this cytokine
      in BM. In the present study we investigated Th17-related cytokines in RA BM.
      METHODS: BM samples were obtained from RA and osteoarthritis (OA) patients during
      total hip replacement surgery. Levels of IL-17AF, IL-17AA, IL-17FF, IL-1beta, IL
      6, IL-23, TGF-beta and CCL20 in BM plasma were determined by specific enzyme
      linked immunosorbent assay tests. Percentage of IL-17-producing cells in BM was
      evaluated by flow cytometry. The effect of IL-15 stimulation on IL-17 production
      by BM mononuclear cells was examined in vitro. RESULTS: Increased levels of IL
      17AF were observed in BM plasma of RA patients in comparison to OA patients.
      Increased concentrations of IL-1beta, IL-6 and CCL20 were observed in RA compared
      to OA BM plasma. Concordant with these findings, significantly increased
      percentages of CD3+CD4+IL-17+ and CD3+CD4+IL-17+IFN-gamma+ cells were present in
      RA BM in comparison to OA BM samples. Finally, abundant in RA BM, IL-15 increased
      IL-17 production by cultured BM mononuclear cells. CONCLUSIONS: In the course of
      RA, the BM microenvironment can promote the development of Th17 cell responses
      and overproduction of IL-17AF that may lead to increased inflammation and tissue
      destruction in RA BM.

PMID- 29216916
TI  - Low level laser therapy (Photobiomodulation therapy) for breast cancer-related
      lymphedema: a systematic review.
AB  - BACKGROUND: Breast cancer related lymphedema (BCRL) is a prevalent complication
      secondary to cancer treatments which significantly impacts the physical and
      psychological health of breast cancer survivors. Previous research shows
      increasing use of low level laser therapy (LLLT), now commonly referred to as
      photobiomodulation (PBM) therapy, for BCRL. This systematic review evaluated the
      effectiveness of LLLT (PBM) in the management of BCRL. METHODS: Clinical trials
      were searched in PubMed, AMED, Web of Science, and China National Knowledge
      Infrastructure up to November 2016. Two reviewers independently assessed the
      methodological quality and adequacy of LLLT (PBM) in these clinical trials.
      Primary outcome measures were limb circumference/volume, and secondary outcomes
      included pain intensity and range of motion. Because data were clinically
      heterogeneous, best evidence synthesis was performed. RESULTS: Eleven clinical
      trials were identified, of which seven randomized controlled trials (RCTs) were
      chosen for analysis. Overall, the methodological quality of included RCTs was
      high, whereas the reporting of treatment parameters was poor. Results indicated
      that there is strong evidence (three high quality trials) showing LLLT (PBM) was
      more effective than sham treatment for limb circumference/volume reduction at a
      short-term follow-up. There is moderate evidence (one high quality trial)
      indicating that LLLT (PBM) was more effective than sham laser for short-term pain
      relief, and limited evidence (one low quality trial) that LLLT (PBM) was more
      effective than no treatment for decreasing limb swelling at short-term follow-up.
      CONCLUSIONS: Based upon the current systematic review, LLLT (PBM) may be
      considered an effective treatment approach for women with BCRL. Due to the
      limited numbers of published trials available, there is a clear need for well
      designed high-quality trials in this area. The optimal treatment parameters for
      clinical application have yet to be elucidated.

PMID- 29216918
TI  - Effect of structured training programme on the knowledge and behaviors of breast
      and cervical cancer screening among the female teachers in Turkey.
AB  - BACKGROUND: Breast cancer and cervical cancer are the most common cancers among
      women in the world. Many studies on the early detection of cancer have been
      conducted among women worldwide, but few studies have been performed in the world
      on female teachers regarding breast self-examination (BSE), mammography (MMG) and
      Pap smear test (PST). As teachers interact with students, this could play an
      important role in health education and in developing healthy behavior such as
      cancer screening. The main objective of this study was to evaluate the effect of
      a structured teaching program on breast and cervical cancer screening on the
      knowledge and practice of teachers. The other objective was to encourage teachers
      to transfer this knowledge to the women who attended their courses. METHODS: Semi
      -experimental designs with pre-intervention, post-intervention and six month
      follow-up tests were used in this study. The data were collected from 37
      volunteer teachers and their 64 volunteer students with a sociodemographic form,
      a questionnaire form for breast and cervical cancer, and a Transtheoretical Model
      of behavior change for BSE, MMG and PST. Behavior of the teachers related to BSE,
      MMG, PST was evaluated in pre-training and in the first, third and sixth months
      post-training, and the behavior of the students was evaluated with point follow
      up in the sixth month. RESULTS: In post-training, it was determined that the
      teachers' knowledge of breast cancer increased from 11.70 +/- 2.80 to 14.81 +/-
      3.22 and their knowledge of cervical cancer increased from 7.75 +/- 5.60 to 17.68
      +/- 3.79. For BSE behavior, 47.8% of teachers were in the action and maintenance
      stage in pre-training, but this ratio was 81.1% in the sixth month post-training.
      For MMG behavior, all of the teachers were in the precontemplation stage in pre
      training, and 38.9% of them were in the action and maintenance stage in the sixth
      month post-training. For PST, while 24.3% were in the action and maintenance
      stage in pre-training, this ratio was 45.9% in the sixth month post-training.
      CONCLUSION: It was determined that the behavior change for BSE, MMG, PST was
      positive. Similarly, knowledge transfer from teachers to students was also
      effective.

PMID- 29216917
TI  - Unexpected profile of sphingolipid contents in blood and bone marrow plasma
      collected from patients diagnosed with acute myeloid leukemia.
AB  - BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in
      an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main
      factor of leukemic cells drug resistance. METHODS: To assess the presence of
      potential abnormalities that might promote dysfunction of leukemic cells growth,
      HPLC system was used to determine sphingosine (SFO), sphinganine (SFA),
      sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood
      collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49)
      and compare to values of control (healthily) group (n = 51). Additionally, in AML
      group concentration of SFO, SFA, S1P and CER was determined in bone marrow plasma
      and compared to respective values in blood plasma. The concentration of S1P and
      CER binding protein - plasma gelsolin (GSN) was also assessed in collected
      samples using immunoblotting assay. RESULTS: We observed that in AML patients the
      average SFO, SFA and CER concentration in blood plasma was significantly higher
      (p < 0.001) compare to control group, when blood plasma S1P concentration was
      significantly lower (p < 0.001). At the same time the CER/S1P ratio in AML
      patient (44.5 +/- 19.4) was about 54% higher compare to control group (20.9 +/-
      13.1). Interestingly the average concentration of S1P in blood plasma (196 +/- 13
      pmol/ml) was higher compare to its concentration in plasma collected from bone
      marrow (154 +/- 21 pmol/ml). CONCLUSIONS: We hypothesize that changes in profile
      of sphingolipids concentration and some of their binding protein partners such as
      GSN in extracellular environment of blood and bone marrow cells in leukemic
      patients can be targeted to develop new AML treatment method(s).

PMID- 29216919
TI  - The acutely injured acromioclavicular joint - which imaging modalities should be
      used for accurate diagnosis? A systematic review.
AB  - BACKGROUND: The management of acute acromioclavicular (AC) joint injuries depends
      on the degree of injury diagnosed by the Rockwood classification. Inadequate
      imaging and not selecting the most helpful imaging protocols can often lead to
      incorrect diagnosis of the injury. A consensus on a diagnostic imaging protocol
      for acute AC joint injuries does not currently exist. Therefore we conducted a
      systematic review of the literature considering three diagnostic parameters for
      patients with acromioclavicular (AC) joint injuries: 1) Assessment of vertical
      instability; 2) Assessment of horizontal instability; 3) Benefit of weighted
      panoramic views. METHODS: Internet databases were searched in March 2016 using
      the terms ("AC joint" OR "acromioclavicular joint") AND (MRI OR MR OR radiograph
      OR X-ray OR Xray OR ultrasound OR "computer tomography" OR "computed tomography"
      OR CT). Diagnostic, prospective, retrospective, cohort and cross- sectional
      studies were included to compare their use of different radiological methods.
      Case reports, cadaveric studies, and studies concerning chronic AC injuries and
      clinical outcomes were excluded. RESULTS: This search returned 1359 citations of
      which 1151 were excluded based on title, 116 based on abstract and 75 based on
      manuscript. 17 studies were included for review and were analyzed for their
      contributions to the three parameters of interest mentioned above. The inter- and
      intra-observer reliability for diagnosing vertical instabilities of the clavicle
      using x-ray alone show a high level of reproducibility while for horizontal
      instabilities the values were much more variable. In general, digitally measured
      parameters seem to be more precise and reliable between investigators than visual
      classification alone. Currently, evidence for the value of weighted views and
      other additional diagnostic imaging to supplement standard x-rays is
      controversial. CONCLUSION: To date there is no consensus on a gold standard for
      diagnostic measures needed to classify acute AC joint injuries. The inter- and
      intra-observer reliability for diagnosing vertical instabilities of the clavicle
      using bilateral projections show a high level of reproducibility while for
      horizontal instabilities the results are much more inconsistent. There is
      currently no clear consensus on a protocol for image-based diagnosis and
      classification of acute AC joint injuries, leading to a lack of confidence in
      reproducibility and reliability.

PMID- 29216921
TI  - Ultrasonography-guided reduction of pediatric radial neck fractures.
AB  - BACKGROUND: Treatment of displaced and angulated radial neck fractures in
      children is controversial and challenging. Numerous studies have been conducted
      regarding treatment algorithms and surgical techniques that use fluoroscopy.
      However, ultrasonography (US)-guided reduction of pediatric radial neck fractures
      has not been reported yet. We aimed to determine the safety and efficacy of US
      guided reduction and fixation of radial neck fractures in children. METHODS:
      Among 28 cases of radial neck fracture from 2014 to 2016, 12 were classified as
      type III or IV according to the Judet classification. All 12 patients underwent
      US-guided reduction and percutaneous fixation with Kirschner wire and follow-up
      for more than 6 months. US was used primarily to monitor the angulation and
      reduction of the radial neck. Fluoroscopy was applied to confirm the fixation
      with Kirschner wire. Dose area product (DAP; mGy/cm2) was measured to assess per
      procedure radiation dose. Radiological and clinical results were evaluated at 6
      months after the surgery by using the Metaizeau criteria. RESULTS: Of the
      patients, 4 were boys and 8 were girls, with a mean age of 7.7 years (range, 5-11
      years). Judet type III fractures accounted for 83% of all injuries. The mean
      preoperative radial angulation was 62.5 degrees  (range: 46 degrees -76 degrees
      ). The mean postoperative radial angulation was 5.6 degrees  (range: 2 degrees -9
      degrees ). The mean fluoroscopy time was 31 s (range: 10-73 s), and the mean DAP
      was 10.7 mGy/cm2 (range: 7.2-18.7 mGy/cm2). The mean follow-up period was 18.3
      months (range, 8-24 months). According to the Metaizeau criteria, 10 cases were
      excellent and 2 cases were good at the last follow-up. CONCLUSIONS: US-guided
      reduction and percutaneous fixation is safe and reliable option to treat
      displaced radial neck fractures in children.

PMID- 29216920
TI  - Body mass index had different effects on premenopausal and postmenopausal breast
      cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31
      cohort studies.
AB  - BACKGROUND: There is sufficient evidence supporting a relationship between
      increased body mass index (BMI) and an increased risk for breast cancer among
      postmenopausal women. However, most studies have found a decreased risk for
      premenopausal breast cancer. This study was conducted to find out the different
      effects of BMI on the risk of breast cancer among premenopausal and
      postmenopausal women, and explore the potential factors that influence the
      associations. METHODS: A dose-response meta-analysis with 3,318,796 participants
      from 31 articles was conducted. Cohort studies that included BMI and
      corresponding breast cancer risk were selected through various databases
      including PubMed, Medline, Web of Science, the China National Knowledge
      Infrastructure (CNKI) and Chinese Scientific Journals (VIP). Random effects
      models were used for analyzing the data. RESULTS: The summary relative risks
      (RRs) were 1.33 (95%CI: 1.20-1.48) and 0.94(95%CI: 0.80-1.11) among
      postmenopausal and premenopausal women, respectively. The dose-response meta
      analysis indicated a positive non-linear association between BMI and breast
      cancer risk among postmenopausal women, and compared to the mean level of the
      normal BMI category (21.5 kg/m2) the RR in total postmenopausal women were1.03
      (95% CI: 1.02-1.05) per 1 kg/m2 increment. However, no statistically significant
      association among total premenopausal women was detected. In subgroup analysis
      among European premenopausal women, the summary RR was 0.79(95%CI: 0.70-0.88).
      The non-linear relationship showed a negative non-linear association between BMI
      and breast cancer risk among European premenopausal women. When compared to the
      mean level of the normal BMI category, the RRs were 0.98 (95%CI: 0.96-1.00) per 1
      kg/m2 increment, respectively. CONCLUSIONS: In line with previous studies BMI had
      different effects on pre-menopausal and postmenopausal breast cancer risk.
      However, contrary to previous studies, a high BMI was not associated with
      decreased risk in total pre-menopausal women. More research is needed to better
      understand these differences.

PMID- 29216922
TI  - Lactic-fermented egg white improves visceral fat obesity in Japanese subjects
      double-blind, placebo-controlled study.
AB  - BACKGROUND: It was reported that egg white protein (EWP) reduced body fat in
      rats. We developed a lactic-fermented egg white (LE) that facilitates the
      consumption of egg whites by fermenting them with lactobacillus, and were able to
      study their intake in humans. In this double-blind, placebo-controlled design, we
      evaluated the effect of LE on visceral fat area (VFA). METHODS: Participants
      included 37 adult males and females aged >=40 years (VFA at navel >=100 cm2).
      They were divided into two groups: the control group and the LE group. The
      control and LE groups consumed drinks containing whey and LE, respectively, for
      12 weeks (providing 8 g protein/day). VFA was measured at baseline and at week 12
      of intake. Abdominal girth was measured at baseline and at weeks 6 and 12.
      RESULTS: LE intake decreased VFA significantly compared with baseline (-8.89 cm2,
      p < 0.05), and VFA was significantly lower than that in the control group (+1.71
      cm2, p < 0.05). The LE group showed significant improvement in the ratio of
      visceral to subcutaneous fat area compared with baseline and the control group (p
      < 0.05). CONCLUSIONS: The results demonstrated that LE reduces VFA and improves
      the ratio of visceral to subcutaneous fat area. As other measurement items were
      not influenced, we concluded that LE improves visceral fat obesity. TRIAL
      REGISTRATION: This clinical trial was retrospectively registered with the
      University hospital Medical Information Network (UMIN) Center, ( UMIN000026949 ;
      registered on 11/04/2017; http://www.umin.ac.jp /).

PMID- 29216923
TI  - Supervised learning for infection risk inference using pathology data.
AB  - BACKGROUND: Antimicrobial Resistance is threatening our ability to treat common
      infectious diseases and overuse of antimicrobials to treat human infections in
      hospitals is accelerating this process. Clinical Decision Support Systems (CDSSs)
      have been proven to enhance quality of care by promoting change in prescription
      practices through antimicrobial selection advice. However, bypassing an initial
      assessment to determine the existence of an underlying disease that justifies the
      need of antimicrobial therapy might lead to indiscriminate and often unnecessary
      prescriptions. METHODS: From pathology laboratory tests, six biochemical markers
      were selected and combined with microbiology outcomes from susceptibility tests
      to create a unique dataset with over one and a half million daily profiles to
      perform infection risk inference. Outliers were discarded using the inter
      quartile range rule and several sampling techniques were studied to tackle the
      class imbalance problem. The first phase selects the most effective and robust
      model during training using ten-fold stratified cross-validation. The second
      phase evaluates the final model after isotonic calibration in scenarios with
      missing inputs and imbalanced class distributions. RESULTS: More than 50% of
      infected profiles have daily requested laboratory tests for the six biochemical
      markers with very promising infection inference results: area under the receiver
      operating characteristic curve (0.80-0.83), sensitivity (0.64-0.75) and
      specificity (0.92-0.97). Standardization consistently outperforms normalization
      and sensitivity is enhanced by using the SMOTE sampling technique. Furthermore,
      models operated without noticeable loss in performance if at least four
      biomarkers were available. CONCLUSION: The selected biomarkers comprise enough
      information to perform infection risk inference with a high degree of confidence
      even in the presence of incomplete and imbalanced data. Since they are commonly
      available in hospitals, Clinical Decision Support Systems could benefit from
      these findings to assist clinicians in deciding whether or not to initiate
      antimicrobial therapy to improve prescription practices.

PMID- 29216924
TI  - Dengue hemorrhagic fever complicated with acute liver failure: a case report.
AB  - BACKGROUND: Dengue is a common arboviral infection with a clinically diverse
      spectrum of presentations. Although hepatic dysfunction is commonly identified in
      patients will dengue illness, acute liver failure is rare. The etiopathogenesis
      of hepatic dysfunction is multifactorial and related to direct viral invasion of
      hepatocytes, immunological factors and hypoxia particularly in cases of shock in
      dengue hemorrhagic fever. Ideal management of dengue-related hepatic dysfunction
      and acute liver failure is still debated. CASE PRESENTATION: We report a 53-year
      old Sri Lankan Sinhalese male with serologically confirmed dengue fever
      presenting with evidence of plasma leakage developing acute liver failure
      evidenced by deranged liver functions, coagulopathy and altered sensorium. In
      addition to the 'standard care', the patient was managed with intravenous N
      acetyl cysteine and blood transfusions even in the absence of bleeding or
      dropping packed cell volume (PCV), targeting a higher PCV in anticipation of
      better oxygenation at tissue level. He made a full recovery with no sequential
      infections. CONCLUSION: N-acetyl cysteine and packed cell transfusion aiming at a
      higher PCV to maintain adequate tissue perfusion during shock may be beneficial
      in acute liver failure due to dengue virus. Large randomized trials should be
      carried out to establish the efficacy of these treatment strategies to support
      these observations and change the current practice.

PMID- 29216925
TI  - Silencing of miR-193a-5p increases the chemosensitivity of prostate cancer cells
      to docetaxel.
AB  - BACKGROUND: Docetaxel-based chemotherapy failure in advanced prostate carcinoma
      has partly been attributed to the resistance of prostate cancer (PC) cells to
      docetaxel-induced apoptosis. Hence, there is an urgent need to identify
      mechanisms of docetaxel chemoresistance and to develop new combination therapies.
      METHODS: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell
      lines, and its expression in the tissues was also examined by in situ
      hybridization. PC cell line (PC3 cell) was transfected with miR-193a-5p mimic or
      its inhibitor, and then cell apoptosis and the expression of its downstream genes
      Bach2 and HO-1 were detected by TUNEL staining and Western blotting. Luciferase
      reporter assay was used to detect the effect of miR-193a-5p and Bach2 on HO-1
      expression. Xenograft animal model was used to test the effect of miR-193a-5p and
      docetaxel on PC3 xenograft growth. RESULTS: miR-193a-5p was upregulated in PC
      tissues and PC cell lines, with significant suppression of PC3 cell apoptosis
      induced by oxidative stress. Mechanistically, miR-193a-5p suppressed the
      expression of Bach2, a repressor of the HO-1 gene, by directly targeting the
      Bach2 mRNA 3'-UTR. Docetaxel treatment modestly decreased Bach2 expression and
      increased HO-1 level in PC3 cells, whereas a modest increase of HO-1 facilitated
      docetaxel-induced apoptosis. Notably, docetaxel-induced miR-193a-5p upregulation,
      which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO
      1 expression, partly counteracted docetaxel-induced apoptosis, as evidenced by
      the increased Bcl-2 and decreased Bax expression. Accordingly, silencing of miR
      193a-5p enhanced sensitization of PC3 cells to docetaxel-induced apoptosis.
      Finally, depletion of miR-193a-5p significantly reduced PC xenograft growth in
      vivo. CONCLUSIONS: Silencing of miR-193a-5p or blockade of the miR-193a-5p-Bach2
      HO-1 pathway may be a novel therapeutic approach for castration-resistant PC.

PMID- 29216928
TI  - On the pivotal role of dose for particle toxicology and risk assessment: exposure
      is a poor surrogate for delivered dose.

PMID- 29216927
TI  - Canonical correlation analysis (CCA) of anthropometric parameters and physical
      activities with blood lipids.
AB  - BACKGROUND: Anthropometric parameters and physical activities are significant
      factors influencing lipid levels, but few research have demonstrated the effect
      of amount of activities on lipid levels. Our research analyzed and explored this
      relationships. METHODS: A multi-stage stratified sampling method was used to
      select the investigation subjects in Hubei, China. A questionnaire survey,
      physical measurements and biochemistry tests (including total cholesterol, high
      low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and
      triacylglycerol) were conducted using CCA analysis. RESULTS: The first canonical
      correlation of the four biochemistry tests and anthropometric parameters with
      physical activities was 0.44 (P < 0.0001). Grouping by sex and areas, the first
      canonical correlation were 0.51 (p < 0.0001), 0.43 (p < 0.0001), 0.39 (p <
      0.0001) and 0.45 (p < 0.0001). By CCA, blood lipids were negatively correlated
      with occupation activity, and positively associated with waistline, body mass
      index (BMI), sleep time, static behavior, and age. CONCLUSIONS: CCA could be an
      efficient method to find out the most influential factors on exposure and outcome
      variables. Blood lipid had significant but moderate association with physical
      activities and anthropometric parameters. Waistline, BMI and occupation activity
      function as major influences on lipids. TRIAL REGISTRATION: Identifying number:
      2,013,001 . Date of trial registry: 8st Oct 2012.

PMID- 29216926
TI  - Pro-inflammatory adjuvant properties of pigment-grade titanium dioxide particles
      are augmented by a genotype that potentiates interleukin 1beta processing.
AB  - BACKGROUND: Pigment-grade titanium dioxide (TiO2) particles are an additive to
      some foods (E171 on ingredients lists), toothpastes, and pharma-/nutraceuticals
      and are absorbed, to some extent, in the human intestinal tract. TiO2 can act as
      a modest adjuvant in the secretion of the pro-inflammatory cytokine interleukin
      1beta (IL-1beta) when triggered by common intestinal bacterial fragments, such as
      lipopolysaccharide (LPS) and/or peptidoglycan. Given the variance in human
      genotypes, which includes variance in genes related to IL-1beta secretion, we
      investigated whether TiO2 particles might, in fact, be more potent pro
      inflammatory adjuvants in cells that are genetically susceptible to IL-1beta
      related inflammation. METHODS: We studied bone marrow-derived macrophages from
      mice with a mutation in the nucleotide-binding oligomerisation domain-containing
      2 gene (Nod2 m/m), which exhibit heightened secretion of IL-1beta in response to
      the peptidoglycan fragment muramyl dipeptide (MDP). To ensure relevance to human
      exposure, TiO2 was food-grade anatase (119 +/- 45 nm mean diameter +/- standard
      deviation). We used a short 'pulse and chase' format: pulsing with LPS and
      chasing with TiO2 +/- MDP or peptidoglycan. RESULTS: IL-1beta secretion was not
      stimulated in LPS-pulsed bone marrow-derived macrophages, or by chasing with MDP,
      and only very modestly so by chasing with peptidoglycan. In all cases, however,
      IL-1beta secretion was augmented by chasing with TiO2 in a dose-dependent fashion
      (5-100 MUg/mL). When co-administered with MDP or peptidoglycan, IL-1beta
      secretion was further enhanced for the Nod2 m/m genotype. Tumour necrosis factor
      alpha was triggered by LPS priming, and more so for the Nod2 m/m genotype. This
      was enhanced by chasing with TiO2, MDP, or peptidoglycan, but there was no
      additive effect between the bacterial fragments and TiO2. CONCLUSION: Here, the
      doses of TiO2 that augmented bacterial fragment-induced IL-1beta secretion were
      relatively high. In vivo, however, selected intestinal cells appear to be loaded
      with TiO2, so such high concentrations may be 'exposure-relevant' for localised
      regions of the intestine where both TiO2 and bacterial fragment uptake occurs.
      Moreover, this effect is enhanced in cells from Nod2 m/m mice indicating that
      genotype can dictate inflammatory signalling in response to (nano)particle
      exposure. In vivo studies are now merited.

PMID- 29216929
TI  - PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3beta/beta
      catenin/cyclin D1 signaling pathway in ER-negative breast cancer.
AB  - BACKGROUND: A growing amount of evidence has indicated that PSAT1 is an oncogene
      that plays an important role in cancer progression and metastasis. In this study,
      we explored the expression and function of PSAT1 in estrogen receptor (ER)
      negative breast cancer. METHOD: The expression level of PSAT1 in breast cancer
      tissues and cells was analyzed using real-time-PCR (RT-PCR), TCGA datasets or
      immunohistochemistry (IHC). The overall survival of patients with ER-negative
      breast cancer stratified by the PSAT1 expression levels was evaluated using
      Kaplan-Meier analysis. The function of PSAT1 was analyzed using a series of in
      vitro assays. Moreover, a nude mouse model was used to evaluate the function of
      PSAT1 in vivo. qRT-PCR and western blot assays were used to evaluate gene and
      protein expression, respectively, in the indicated cells. In addition, we
      demonstrated that PSAT1 was activated by ATF4 by chromatin immunoprecipitation
      (ChIP) assays. RESULTS: mRNA expression of PSAT1 was up-regulated in ER-negative
      breast cancer. A tissue microarray that included 297 specimens of ER-negative
      breast cancer was subjected to an immunohistochemistry assay, which demonstrated
      that PSAT1 was overexpressed and predicted a poor clinical outcome of patients
      with this disease. Our data showed that PSAT1 promoted cell proliferation and
      tumorigenesis in vitro and in vivo. We further found that PSAT1 induced up
      regulation of cyclin D1 via the GSK3beta/beta-catenin pathway, which eventually
      led to the acceleration of cell cycle progression. Furthermore, ATF4 was also
      overexpressed in ER-negative breast cancers, and a positive correlation between
      the ATF4 and PSAT1 mRNA levels was observed in ER-negative breast cancers. We
      further demonstrated that knockdown of ATF4 by siRNA reduced PSAT1 expression.
      Finally, chromatin immunoprecipitation (ChIP) assays showed that PSAT1 was a
      target of ATF4. CONCLUSIONS: PSAT1, which is overexpressed in ER-negative breast
      cancers, is activated by ATF4 and promotes cell cycle progression via regulation
      of the GSK3beta/beta-catenin/cyclin D1 pathway.

PMID- 29216930
TI  - Contacting of authors by systematic reviewers: protocol for a cross-sectional
      study and a survey.
AB  - BACKGROUND: Synthesizing outcomes of underreported primary studies can pose a
      serious threat to the validity of outcomes and conclusions of systematic reviews.
      To address this problem, the Cochrane Collaboration recommends reviewers to
      contact authors of eligible primary studies to obtain additional information on
      poorly reported items. In this protocol, we present a cross-sectional study and a
      survey to assess (1) how reviewers of new Cochrane intervention reviews report on
      procedures and outcomes of contacting of authors of primary studies to obtain
      additional data, (2) how authors reply, and (3) the consequences of these
      additional data on the outcomes and quality scores in the review. All research
      questions and methods were pilot tested on 2 months of Cochrane reviews and were
      subsequently fine-tuned. METHODS FOR THE CROSS-SECTIONAL STUDY: Eligibility
      criteria are (1) all new (not-updates) Cochrane intervention reviews published in
      2016, (2) reviews that included one or more primary studies, and (3) eligible
      interventions refer to contacting of authors of the eligible primary studies
      included in the review to obtain additional research data (e.g., information on
      unreported or missing data, individual patient data, research methods, and bias
      issues). Searching for eligible reviews and data extraction will be conducted by
      two authors independently. The cross-sectional study will primarily focus on how
      contacting of authors is conducted and reported, how contacted authors reply, and
      how reviewers report on obtained additional data and their consequences for the
      review. METHODS FOR THE SURVEY: The same eligible reviews for the cross-sectional
      study will also be eligible for the survey. Surveys will be sent to the contact
      addresses of these reviews according to a pre-defined protocol. We will use
      Google Forms as our survey platform. Surveyees are asked to answer eight
      questions. The survey will primarily focus on the consequences of contacting
      authors of eligible primary studies for the risk of bias and Grading of
      Recommendations, Assessment, Development and Evaluation scores and the primary
      and secondary outcomes of the review. DISCUSSION: The findings of this study
      could help improve methods of contacting authors and reporting of these
      procedures and their outcomes. Patients, clinicians, researchers, guideline
      developers, research sponsors, and the general public will all be beneficiaries.

PMID- 29216931
TI  - VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene
      expression in response to simulated immune complexes.
AB  - BACKGROUND: In addition to activated T cells, the immune checkpoint inhibitor "V
      domain-containing Ig suppressor of T-cell activation" (VISTA) is expressed by
      myeloid cell types, including macrophages and neutrophils. The importance of
      VISTA expression by myeloid cells to antibody-induced arthritis and its potential
      for relevance in human disease was evaluated. METHODS: VISTA was immunolocalized
      in normal and arthritic human synovial tissue sections and synovial tissue
      lysates were subjected to western blot analysis. The collagen antibody-induced
      arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies
      against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic
      joints, spleens, and cultured macrophages was analyzed with NanoString arrays.
      Cytokines secreted by splenic inflammatory macrophages were determined. In-vitro
      chemotaxis and signal transduction assays were performed with cultured
      macrophages. RESULTS: VISTA protein was localized to synovial membrane cells,
      neutrophils, and scattered cells in lymphocyte-rich foci and was detected by
      western blot analysis in normal synovium and synovium from rheumatoid arthritis
      patients. Deficiency of VISTA or treatment of mice with anti-VISTA monoclonal
      antibodies attenuated CAIA. Joint damage and MMP-3 expression were significantly
      reduced in V-KO mice. Surface expression of C5a receptor was reduced on
      monocytes, neutrophils, and cultured macrophages from V-KO. Upon Fc receptor
      engagement in vitro, gene expression by V-KO macrophages was altered profoundly
      compared to WT, including a significant induction of IL-1 receptor antagonist
      (IL1rn). CONCLUSIONS: VISTA expression supports immune-complex inflammation in
      CAIA and VISTA is expressed in human synovium. VISTA supports optimal responses
      to C5a and modulates macrophage responses to immune complexes.

PMID- 29216933
TI  - The Impact of Victim Alcohol Consumption and Perpetrator Use of Force on
      Perceptions in an Acquaintance Rape Vignette.
AB  - Research suggests that victims of incapacitated rape (when someone has sex with a
      person who is unable to consent to or resist sexual activity, usually because of
      intoxication) face higher levels of victim blame than do victims of forcible rape
      (Krahe, Temkin, & Bieneck, 2007). However, it is not clear whether blame is the
      result of victim alcohol consumption or the lack of force and resistance present
      during incapacitated rape; both of these factors have been shown to increase
      victim blame. The current vignette study crossed victim alcohol consumption and
      perpetrator use of force. We found main effects of both independent variables on
      judgments of victim responsibility, but no interaction, suggesting that the
      effects of alcohol and force are additive rather than interactive. These results
      indicate that victims of incapacitated rape may indeed face challenges upon
      disclosing their assaults.

PMID- 29216932
TI  - Nanobodies targeting conserved epitopes on the major outer membrane protein of
      Campylobacter as potential tools for control of Campylobacter colonization.
AB  - Campylobacter infections are among the most prevalent foodborne infections in
      humans, resulting in a massive disease burden worldwide. Broilers have been
      identified as the major source of campylobacteriosis and reducing Campylobacter
      loads in the broiler caeca has been proposed as an effective measure to decrease
      the number of infections in humans. Failure of current methods to control
      Campylobacter in broilers stresses the urgency to develop novel mitigation
      measures. We obtained six nanobodies with a broad specificity, that recognize
      strains belonging to the two most relevant species, Campylobacter jejuni and
      Campylobacter coli. The target of the nanobodies was identified as the major
      outer membrane protein, a porin that contributes to bacterial virulence and
      viability. Multimerization of the nanobodies led to agglutination of C. jejuni
      cells, which may affect colonization in the chicken gut. These Campylobacter
      specific nanobodies may be useful to develop a strategy for preserving chickens
      from Campylobacter colonization.

PMID- 29216934
TI  - From Commensal to Consumer: Staphylococcus aureus Toxins, Diseases, and Detection
      Methods.
AB  - Staphylococcus aureus is a Gram-positive bacterium capable of causing a wide
      array of infections. Generally a commensal organism, S. aureus encodes several
      virulence mechanisms that contribute to disease progression. This review
      highlights toxins as a secreted virulence factor by S. aureus, the diseases that
      manifest as a result, and the methods used to detect them. In particular, the
      advantages and limitations of current toxin detection methods are discussed.

PMID- 29216935
TI  - [Chest compression on CPR and active abdominal on CPR].
AB  - OBJECTIVE: Chest compression cannot be effectively applied under certain
      situations, such as chest wall deformity, rib fracture, or hemopneumothorax.
      Active abdominal compression-decompression cardiopulmonary resuscitation (AACD
      CPR) could reach better resuscitation outcomes in certain cardiac arrest (CA)
      patients. AACD-CPR can strengthen the high quality of cardiopulmonary
      resuscitation (CPR) in "2015 American Heart Association for cardiopulmonary
      resuscitation and emergency cardiovascular care update guide". The two methods
      can complement each other in opposite direction, and implement the "2016 national
      consensus on cardiopulmonary resuscitation on CPR in China", which is an
      important part of the wisdom to the Chinese CPR. In the article, we compared
      chest compression in standard single rescuer cardiopulmonary resuscitation (STD
      CPR) and AACD-CPR with their aspects of the cause, mechanism, methods and
      application. We will provide an important reference about techniques of STD-CPR
      and AACD-CPR.

PMID- 29216936
TI  - [Experimental basis and clinical practice of "bacterial poison and cure" sepsis].
AB  - OBJECTIVE: Since the 20th century, research team of Professor Wang Jinda in the
      Tianjin First Central Hospital has been using blood circulation drugs to rescue
      critically ill patients for 70 years. With the deepening of the understanding of
      sepsis, put forward the "bacteria and inflammation and governance" theory, and
      the use of blood circulation drugs Xuebijing injection with anti-endotoxin and
      inflammatory mediators effect in the treatment of sepsis, some clinical efficacy
      has been found. However, in recent years, the progress of treatment of sepsis at
      home and abroad is slow, we review a series of animal experiments since the late
      of 1980s, and found that small thrombosis in the microcirculation and coagulation
      disorders play a more important role in the development of local infection to
      sepsis transition. Treatment combined with Xuebijing injection is proved
      effective with more and more clinical practice, so the important status of blood
      stasis and blood circulation method in sepsis must be paid attention to again.

PMID- 29216937
TI  - [Significance of peripheral perfusion index in early diagnosis and goal-directed
      therapy of septic shock patients: a prospective single-blind randomized
      controlled trial].
AB  - OBJECTIVE: To investigate the application of peripheral perfusion index (PPI) in
      early diagnosis and goal-directed therapy of septic shock, and to provide
      reference for the early clinical diagnosis and treatment of septic shock.
      METHODS: A prospective single-blind randomized controlled trial (RCT) was
      conducted. Adult patients with sepsis admitted to emergency medical department
      and intensive care unit (ICU) of the First People's Hospital of Lianyungang City
      in Jiangsu Province from January 2013 to December 2016 were enrolled. The
      patients were randomly divided into two groups (n = 46). The PPI group was
      defined using PPI < 1.4 as diagnosis of septic shock standard, and PPI > 2 as
      treatment guide target. Control group was defined according to the traditional
      diagnostic criteria of shock which systolic blood pressure was less than 90 mmHg
      (1 mmHg = 0.133 kPa) or systolic blood pressure value decrease > 40 mmHg baseline
      and bundle treatment was performed. The volume of fluid resuscitation, organ
      dysfunction, the sequential organ failure score (SOFA), acute physiology and
      chronic health evaluation II (APACHE II) score, continuous renal replacement
      therapy (CRRT) time, mechanical ventilation (MV) time, the length of ICU stay and
      28-day mortality were observed. RESULTS: There were 39 and 27 septic shock
      patients in PPI group and control group respectively. The diagnostic criteria of
      traditional septic shock with blood pressure as "gold standard", the sensitivity
      of PPI < 1.4 for septic shock was 94.3%, the specificity was 28.2%, the
      authenticity was 66.3%, the positive predictive value was 64.1%, the negative
      predictive value was 78.6%, the positive likelihood ratio was 1.31, the negative
      likelihood ratio was 0.18. The per capita fluid replacement within 24 hours in
      the PPI group was significantly higher than that in the control group (mL: 4
      601+/-1 250 vs. 3 458+/-1 006, P < 0.01), but there was no significant difference
      in the per capita volume of the patients diagnosed as septic shock (mL: 4 596+/-1
      320 vs. 4 205+/-1 058, P > 0.05). Compared with the control group, the PPI group
      treated patients within 48 hours with less vascular active drugs (cases: 6 vs.
      15), APACHE II and SOFA score were lower (48 hours: APACHE II was 10.2+/-2.1 vs.
      12.0+/-3.2; 72 hours: SOFA was 5.1+/-1.8 vs. 6.0+/-2.1, APACHE II was 8.9+/-1.8
      vs. 9.8+/-2.2), the period of CRRT and the length of ICU stay were shorter [the
      period of CRRT (days): 3.0+/-0.9 vs. 3.6+/-1.4, the length of ICU stay (days):
      5.2+/-2.1 vs. 6.3+/-2.9), the difference was statistically significant (all P <
      0.05). There was no significant difference in the liver and kidney function
      index, arterial blood lactic acid (Lac), MV time (days: 3.3+/-1.4 vs. 3.5+/-1.2)
      and 28-day mortality (15.22% vs. 19.57%) between two groups (all P > 0.05).
      CONCLUSIONS: The inadequacy of microcirculatory perfusion by oximetry-derived PPI
      is more sensitive to the diagnosis of septic shock than hypotension of systemic
      circulation. With PPI guiding the fluid resuscitation of septic shock patients,
      vasopressors can be withdrawn earlier and the duration of the CRRT and ICU can be
      decreased.

PMID- 29216938
TI  - [A model based on random forests in prediction of 28-day prognosis in patients
      with severe sepsis/septic shock].
AB  - OBJECTIVE: To establish a severe sepsis/septic shock prognosis prediction model
      based on randomize forest law (RF model), and to evaluate the prognostic value of
      this model for patients with severe sepsis/septic shock. METHODS: 497 patients
      with severe sepsis/septic shock admitted to intensive care unit (ICU) of Zhejiang
      Hospital from September 2013 to May 2017 were enrolled. The basic data, vital
      signs and symptoms, biochemical indexes and blood routine indexes on the 1st,
      3rd, 5th day and prognosis were collected. According to the 28-day prognosis, the
      patients were divided into death group and survival group, and the specific
      indicators about the prognosis of severe sepsis/septic shock were screened. A RF
      model was constructed by using the specificity indicators. The assessment
      effectiveness of RF model, sequential organ failure assessment (SOFA), acute
      physiology and chronic health evaluation II (APACHE II) were evaluated by
      receiver operating characteristic (ROC) curve analysis. RESULTS: In 497 cases of
      severe sepsis/septic shock, 201 cases died, 28-day mortality was 40.4%. (1)
      According to the index difference of death group and survival group, 19 specific
      parameters of the RF model were selected, which included the age; 24-hour urine
      output, urea nitrogen (BUN), serum creatinine (SCr), platelet count (PLT) on the
      1st day; heart rate (HR), mean arterial pressure (MAP), cyanosis and clammy skin
      on the 3rd day; temperature, HR, MAP, 24-hour urine output, PLT, fever, cyanosis,
      dyspneic, clammy skin, piebald on the 5th day. (2) ROC curve analysis showed that
      the area under the ROC curve (AUC) of RF model predicting 28-day mortality was
      higher than that of SOFA and APACHE II score on the 1st, 3rd, 5th day (AUC: 0.836
      vs. 0.643, 0.554, 0.766 and 0.590, 0.670, 0.758). The sensitivity of RF model to
      predict the 28-day mortality was 86.1%, the specificity was 77.0%, the accuracy
      was 80.7%. CONCLUSIONS: The evaluation model based on random forest can
      effectively predict the death risk of 28-day in patients with severe
      sepsis/septic shock, and its predictive efficiency is better than that of the
      SOFA and APACHE II score.

PMID- 29216939
TI  - [Predictive value of dynamic serum phosphorus levels in the prognosis of patients
      with sepsis].
AB  - OBJECTIVE: To explore the predictive value of dynamic serum phosphorus levels in
      the evaluation of prognosis in patients with sepsis. METHODS: A retrospective
      study was conducted. The septic patients admitted to intensive care unit (ICU) of
      the Second People's Hospital of Changzhou from January 2016 to June 2017 were
      enrolled, who were >=18 years old and whose length of ICU stay > 72 hours. These
      patients were divided into survival group and death group according to 28-day
      outcome. The general information, the acute physiology and chronic health
      evaluation II (APACHE II) score within 24 hours of ICU admission, the serum
      phosphorus at 1, 3, 5, 7 days after admission were collected. Receiver operating
      characteristic curve (ROC) was plotted according to the dynamic serum phosphorus
      levels and APACHE II score for evaluating the predictive value of 28-day
      prognosis. Kaplan-Meier survival curve was used to analyze the 28-day cumulative
      survival rate between two groups of patients, who were divided according to the
      corresponding time of the serum phosphorus cut-off value. RESULTS: (1) Eighty
      five patients with sepsis were enrolled, among whom 25 cases were in the death
      group and the mortality was 29.4%. APACHE II score in the death group was
      significantly higher than that in the survival group (22.28+/-3.98 vs. 16.05+/
      5.44, P < 0.01), the rate of using vasoactive drugs was significantly higher than
      that in the survival group [64.0% (16/25) vs. 31.7% (19/60), P < 0.01], but there
      was no significant difference in the length of invasive mechanical ventilation
      and ICU stay between two groups. (2) The level of serum phosphorus was increased
      in survival group along with time of the treatment, and the death group showed a
      downward trend. The levels of serum phosphorus at 3, 5, 7 days after admission to
      ICU in death group were significantly lower than those in survival group (mmol/L:
      0.90+/-0.24 vs. 1.05+/-0.19 at 3 days, 0.96+/-0.16 vs. 1.11+/-0.17 at 5 days,
      0.83+/-0.19 vs. 1.21+/-0.14 at 7 days, all P < 0.01).(3) ROC curve analysis
      showed that APACHE II score and serum phosphorus level on the 7th day could
      significantly predict 28-day mortality in patients with sepsis, and the areas
      under ROC curve (AUC) of them were 0.813 and 0.945 respectively (both P < 0.01).
      The AUC of serum phosphorus level on the 3rd day and 5th day were 0.692 and 0.745
      respectively (both P < 0.01). Based on serum phosphorus cut-off value 1.01 mmol/L
      on the 7th day to evaluate the predictive value of 28-day mortality, the
      sensitivity was 91.7%, the specificity was 84.0%, the positive and negative
      likelihood ratios were 5.73 and 0.10 respectively. (4) Kaplan-Meier survival
      analysis showed that the 28-day survival rate was significantly higher and the
      length of survival was significantly longer if the serum phosphorus were higher
      than the cut-off value at different time points of ICU admission. The 28-day
      survival rate was significantly higher and the length of survival was
      significantly longer in the patients with serum phosphorus > 1.01 mmol/L than
      those serum phosphorus <= 1.01 mmol/L on the 7th day [28-day survival rate: 93.2%
      (55/59) vs. 22.7% (5/22), chi 2 = 49.697, P = 0.000; survival period (days):
      27.1+/-3.6 vs. 19.8+/-7.8, t = 4.768, P = 0.000]. CONCLUSIONS: The continuous
      decline of serum phosphorus indicates poor prognosis, and the serum phosphorus
      level on the 7th day is one of the most important indicator to evaluate the
      prognosis of patients with sepsis.

PMID- 29216940
TI  - [Study on risk factor of central venous catheter infection in ICU: 1 160 patients
      report].
AB  - OBJECTIVE: To analyze the etiology and risk factors of central venous catheter
      (CVCs) infections, and to explore the prophylaxis and treatment for catheter
      related infections. METHODS: A retrospective study was conducted. The patients
      with CVCs admitted to intensive care unit (ICU) of Qianfoshan Hospital Affiliated
      to Shandong University from January 2000 to December 2016 were enrolled. The
      gender, age, catheter data and microorganism culture results of all patients were
      collected. The infection rate and the incidences of CVCs infection per 1 000
      catheter days were calculated. The risk factors of CVCs infection were analyzed
      by Logistic regression. RESULTS: 1 160 patients were enrolled in 17 years [male
      915, female 245, age 7-98 years, mean (71.8+/-17.5) years]. The incidences of
      CVCs infection per 1 000 catheter days were descended every 3 years (cases/1 000
      days: 21.87, 24.50, 19.95, 12.64, 16.34, 12.40, chi2 = 38.851, P = 0.000). Of the
      1 160 patients, 375 were positive for catheter culture, and 397 strains were
      cultured, among which 173 strains (43.58%) were Gram negative (G-), 130 strains
      (32.74%) of Gram positive (G+), and 94 strains of fungi (23.68%). Non-fermenting
      bacteria (Pseudomonas aeruginosa 11.59%, Acinetobacter baumannii 8.82%) was
      predominant in the G- bacteria, followed by Enterobacteria (Klebsiella pneumoniae
      8.06%, Escherichia coli 2.02%); Staphylococcus spp. (Staphylococcus epidermidis
      11.84%, Staphylococcus aureus 5.29%) was the main species of G+ bacteria; the
      main fungi were Candida tropicalis (9.07%) and Candida albicans (5.79%). The
      catheter infection rate of internal jugular vein, femoral vein and subclavian
      vein were 36.07% (22/61), 35.52% (119/335), 30.63% (234/764) respectively (chi2
      =2.275, P = 0.099), the incidence of catheter infection of three vein insertion
      sites per 1 000 catheter days were 18.00, 17.71, 17.08 cases/1 000 days
      respectively (chi2 = 0.034, P = 0.714). The mean placement time of infected CVCs
      in situ was longer than that of non-infected CVCs (days: 20.80+/-11.68 vs.
      17.64+/-10.77, t = 4.417, P = 0.000).The positive rate was lowest during 1-7 days
      of indwelling time (19.87%, 30/151). The infection rate was increased with long
      indwelling time. The positive rate was 44.44% (68/153) as indwelling time was
      over 30 days. The infection rate was significantly positively related to
      indwelling time (chi2 = 22.849, P = 0.000). Multiple Logistic regression analysis
      showed that the infection risk of femoral vein catheter was increased [odds ratio
      (OR) = 1.362, 95% confidence interval (95%CI) = 1.030-1.801, P = 0.030] as
      compared with that of subclavian vein catheter; the infection risk was increased
      with long indwelling time (OR = 1.306, 95%CI = 1.177-1.480, P = 0.000).
      CONCLUSIONS: G- are the major pathogens of CVCs infection. Femoral vein catheter
      and long indwelling time are the risk factors of CVCs infection.

PMID- 29216941
TI  - [Impact of unfractionated heparin on serum and liver tissue expression of
      heparanase in the liver injury of mice with sepsis].
AB  - OBJECTIVE: To investigate the effect of unfractionated heparin on the expression
      of serum and liver tissue heparanase (HPA) in mice with liver injury induced by
      sepsis. METHODS: Forty-eight healthy male C57BL/6 mice aged 6-8 weeks were
      divided into groups according to random number table method. Twenty-four septic
      mice models (CLP group) were established by cecal ligation and puncture (CLP);
      the other 24 mice underwent sham operation (sham group), only laparotomy and
      abdominal closure were performed without ligation. Twelve mice in sham group and
      CLP group received heparin pretreatment (sham+UFH group, CLP+UFH group), and 8 U
      heparin unfractionated heparin (diluted to 200 MUL) was injected into the tail
      vein of the mice at 30 minutes and 12 hours after operation respectively. The
      other 12 mice were injected with the same amount of normal saline. The serum and
      liver tissues of mice were collected at 4 and 24 hours after CLP. The levels of
      serum HPA, interleukin (IL-6, IL-1beta), tumor necrosis factor-alpha (TNF-alpha),
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured
      by enzyme linked immunosorbent assay (ELISA). The pathological changes of liver
      tissue were observed with hematoxylin eosin (HE) staining. The expression of HPA
      in liver tissue was detected by immunohistochemistry. RESULTS: Compared with the
      sham group, the levels of serum HPA, IL-6, IL-1beta, TNF-alpha, ALT and AST in
      the CLP group were increased significantly, and increased further over time. The
      histopathology examination was performed, and abnormal structure, inflammatory
      cell infiltration, liver cell necrosis could be found in the tissue. The
      expression level of HPA in liver tissue was detected by immunohistochemistry,
      which was increased after CLP. This indicated that the animal model of sepsis was
      successfully prepared. Compared with CLP group, serum HPA, inflammatory factors
      and transaminase levels were significantly decreased at 4 hours after operation
      in group CLP+UFH [HPA (ng/L): 76.72+/-2.75 vs. 101.55+/-7.54, IL-6 (ng/L):
      51.16+/-5.68 vs. 63.89+/-3.26, IL-1beta (ng/L): 31.53+/-2.90 vs. 40.87+/-2.88,TNF
      alpha (ng/L): 171.76+/-5.60 vs. 194.62+/-14.13, ALT (MUg/L): 0.26+/-0.09 vs.
      0.62+/-0.17, AST (MUg/L): 1.03+/-0.22 vs. 1.45+/-0.08, all P < 0.05]. At 24
      hours, it was significantly higher than that of 4 hours, but they were
      significantly lower than those in CLP group [HPA (ng/L): 125.30+/-7.80 vs.
      302.50+/-17.81, IL-6 (ng/L): 81.16+/-4.54 vs. 176.56+/-5.45, IL-1beta (ng/L):
      61.13+/-2.80 vs. 113.73+/-3.96, TNF-alpha (ng/L): 328.47+/-10.79 vs. 599.62+/
      10.20, ALT (MUg/L): 0.38+/-0.17 vs. 0.91+/-0.26, AST (MUg/L): 1.16+/-0.15 vs.
      1.88+/-0.08, all P < 0.05]. It was shown by HE staining that the edema of liver
      tissue decreased and inflammatory cell infiltration decreased. It was shown by
      immunohistochemistry that the expression level of HPA in liver tissue was
      significantly decreased [A value (*10-3): 2.49+/-0.93 vs. 6.05+/-1.22 at 4 hours,
      1.86+/-0.77 vs. 7.55+/-0.35 at 24 hours, both P < 0.05]. There was no significant
      difference in indexes between the sham+UFH group and the sham group. CONCLUSIONS:
      The expression of HPA was significantly increased during sepsis in mice.
      Unfractionated heparin may mitigate liver injury by inhibiting HPA.

PMID- 29216942
TI  - [Comparison of national early warning score, rapid emergency medicine score and
      acute physiology and chronic health evaluation II score for predicting outcome
      among emergency severe patients].
AB  - OBJECTIVE: To analyze the comparation of national early warning score (NEWS),
      rapid emergency medicine score (REMS) and acute physiology and chronic health
      evaluation II (APACHE II) score in predicting prognosis of critically ill
      patients in emergency department (ED). METHODS: A retrospective study was
      conducted. Critically ill patients, aged > 16 years, hospitalized > 24 hours, and
      admitted to the ED of Nanhua Hospital Affiliated to South China University from
      January 2016 to June 2017 were enrolled. NEWS, REMS and APACHE II score were
      calculated based on the worst value of each index within 24 hours after emergency
      admission. The primary endpoint was 28-day mortality. The relationship between
      the three scoring systems and the prognosis of patients was analyzed. The
      predictive value of three scoring systems for the prognosis of critically ill
      patients in ED was analyzed by receiver operating characteristic curve (ROC).
      RESULTS: A total of 119 emergency severe patients were enrolled in the study, and
      the 28-day mortality was 21.0%. The scores of NEWS, REMS and APACHE II in the
      death group were significantly higher than those in the survival group (NEWS
      score: 9.40+/-3.19 vs. 5.72+/-2.35, REMS score: 12.64+/-4.46 vs. 7.97+/-3.28,
      APACHE II score: 26.64+/-6.92 vs. 16.19+/-5.48, all P < 0.01). With the increase
      of NEWS, REMS and APACHE II score, the 28-day mortality of patients gradually
      increased [28-day mortality of NEWS < 5, 5-6, >= 7 was 3.03% (1/34), 13.33%
      (4/34), 64.25% (20/51); 28-day mortality of REMS < 12, 12-16, >= 17 was 10.99%
      (10/91), 50.00% (11/22), 66.67% (4/6); 28-day mortality of APACHE II < 15, 15-24,
      >= 25 was 2.33% (1/43), 15.09% (8/59), 69.57% (16/23), respectively, all P <
      0.01]. The ROC curve analysis showed that the areas under the ROC curve (AUC) of
      NEWS, REMS and APACHE II score for predicting the prognosis of emergency
      critically ill patients were 0.830 [95% confidence interval (95%CI) = 0.737
      0.923], 0.782 (95%CI = 0.671-0.892) and 0.878 (95%CI = 0.800-0.956), respectively
      (all P = 0.000), and the accuracy of prediction was 57.4%, 48.6%, 65.4%,
      respectively. CONCLUSIONS: The scores of NEWS, REMS and APACHE II were useful in
      predicting prognosis of critically ill patients, with the highest accuracy of
      APACHE II forecast, followed by NEWS, and the lowest of REMS. After comprehensive
      consideration of cost-effectiveness, NEWS is more reliable in ED.

PMID- 29216943
TI  - [Effect of D-dimer and tissue factor-1208D/I gene polymorphism on the prognosis
      of patients with off-pump coronary artery bypass grafting].
AB  - OBJECTIVE: To investigate the effect of perioperative period D-dimer and tissue
      factor (TF)-1208D/I gene polymorphism on the long-term prognosis of patients with
      off-pump coronary artery bypass grafting (OPCABG). METHODS: Retrospective
      analysis of the case data of the first OPCABG patients admitted to Tianjin
      Medical University General Hospital from May 2015 to May 2016 were enrolled. The
      general data, operation time, bypass number, left ventricular ejection fraction
      (LVEF), flow rate of 24-hour pleural effusion, intraoperative heparin dosage,
      combined anticoagulant and antiplatelet time, and the time of postoperative
      ventilator were measured. The blood biochemical indexes of 1, 4, 7, 14 days and
      1, 2, 3 months after operation, perioperative complications, the level of D-dimer
      in the patients with different TF-1208D/I gene polymorphism, and prognosis of 1
      year follow-up were recorded. The risk factors of recurrent angina 1 year after
      operation was analyzed by Logistic regression analysis. RESULTS: The level of
      plasma D-dimer was increased continuously after OPCABG, and reached a peak at 1
      month after operation [1.94 (1.07, 2.70) mg/L], then decreased, and decreased to
      preoperative level 3 months after operation [0.20 (0.10, 0.45) mg/L]. The level
      of D-dimer in TF-1208II genotype was significantly higher than that in TF-1208DD
      genotype and TF-1208D/I genotype group at 14 days and 1 month after operation
      [mg/L: 4.17 (1.54, 5.09) vs. 1.91 (1.07, 2.26), 1.02 (0.91, 1.88) at 14 days;
      5.12 (2.41, 6.32) vs. 1.94 (1.18, 2.70), 1.62 (0.22,1.88) at 1 month, all P <
      0.05]. The results of 1-year follow-up showed that 25 patients with recurrent
      angina pectoris without the occurrence of myocardial infarction. The proportion
      of recurrent angina pectoris in TF-1208II genotype was significantly higher than
      that in TF-1208DD genotype and TF-1208D/I genotype group (chi2 = 0.197, P =
      0.004). Logistic regression analysis showed that LVEF < 0.50 [odds ratio (OR) =
      6.482, 95% confidence interval (95%CI) = 1.365-18.763, P = 0.015] and TF-1208II
      genotype (OR = 8.864, 95%CI = 1.613-46.743, P = 0.012) were independent risk
      factors for recurrent angina pectoris at 1 year after OPCABG. CONCLUSIONS: After
      OPCABG, the body was in a hypercoagulable state and lasted for a long time, and
      almost recovered 3 months after operation. LVEF < 0.50 and TF-1208 II genotype
      were independent risk factors of angina pectoris at 1 year after surgery.

PMID- 29216944
TI  - [Prognostic value of oxygen challenge test for patients with cardiogenic shock
      receiving extracorporeal membrane oxygenation].
AB  - OBJECTIVE: To investigate the prognostic value of oxygen challenge test (OCT) for
      patients with cardiogenic shock receiving extracorporeal membrane oxygenation
      (ECMO). METHODS: A retrospective analysis was conducted. Seventy-eight patients
      diagnosed with cardiogenic shock receiving veno-arterial (V-A) ECMO admitted to
      Department of intensive care unit (ICU) of Wuxi People's Hospital Affiliated to
      Nanjing Medical University from June 2012 to May 2017 were enrolled. Ten-minute
      OCT was implemented by transcutaneous oximetry at 6 hours after ECMO initiation.
      The basic data of patients (gender, age, primary disease); the acute physiology
      and chronic health evaluation II (APACHE II) score, sequential organ failure
      assessment (SOFA) score, left ventricular ejection fraction (LVEF), mean arterial
      pressure (MAP) at the start of ECMO treatment; arterial blood gas analysis index,
      dose of vasoactive agents, transcutaneous oxygen pressure (PtO2), 10-minute OCT
      value (OCT10), oxygen challenge index (OCI) at 6 hours after ECMO initiation; and
      the ECMO support time, duration of mechanical ventilation and its parameters, and
      application of intra-aortic balloon pump (IABP) within 60 days were recorded.
      Patients were divided into the survival group and the death group according to
      their 60-day mortality status, and the differences between the two groups were
      compared. Receiver operating characteristic curve (ROC) analysis was used to
      analyze the prognostic value of OCT10 and OCI. According to the best boundary
      value of OCT10 and OCI, Kaplan-Meier survival curve was drawn and the 60-day
      cumulative survival rate was compared. The risk factors affecting prognosis were
      analyzed by multivariate Logistic regression. RESULTS: Sixty-seven patients were
      finally enrolled in the study, with 31 in the survival group and 36 in the death
      group. Compared with the survival group, APACHE II score, SOFA score, use of IABP
      in death group were higher, PtO2, OCT10 and OCI were lower, and duration of ECMO
      and ventilation were longer, but there was no significant difference in gender,
      age, primary disease, LVEF, MAP, ventilator settings, dose of vasoactive agents,
      or results of arterial blood gas between the two groups. OCT10, OCI, APACHE II
      score and SOFA score were predictive values for 60-day deaths, and the area under
      ROC curve (AUC) of OCT10 was 0.866+/-0.042 [95% confidence interval (95%CI) =
      0.760-0.937], the AUC of OCI was 0.829+/-0.051 (95%CI = 0.717-0.910), the AUC of
      APACHE II score was 0.860+/-0.043 (95%CI = 0.754-0.933), and the AUC of SOFA
      score was 0.821+/-0.049 (95%CI = 0.708-0.904) (all P < 0.01). The cut-off point
      for OCT10 was >=70.0 mmHg (1 mmHg = 0.133 kPa) with the sensitivity of 91.67% and
      the specificity of 67.74%. The cut-off point for OCI was >=0.68 with the
      sensitivity of 88.68% and the specificity of 71.58%. According to the cut-off
      point for OCT10 or OCI, the 60-day cumulative survival rate of patients with high
      OCT10 was significantly higher than that of low OCT10 [58.06% (18/31) vs. 36.11%
      (13/36), chi2 = 5.425, P = 0.020]; the survival rate in high OCI group was
      significantly higher than that in low OCI group [55.17% (16/29) vs. 39.47%
      (15/38), chi2 = 5.119, P = 0.024]. It was shown by multivariate Logistic
      regression that OCT10 [odds ratio (OR) = 0.883, 95%CI = 0.791-0.965, P = 0.006]
      and OCI (OR = 0.011, 95%CI = 0.001-0.087, P = 0.005) were independent risk
      factors for 60-day mortality. CONCLUSIONS: OCT could predict the prognosis of
      patients with cardiogenic shock receiving ECMO.

PMID- 29216945
TI  - [Expression and meaning of T-bet and GATA3 mRNA in T lymphocyte of patients
      during the operation with cardiopulmonary bypass].
AB  - OBJECTIVE: To investigate the effects of cardiopulmonary bypass (CPB) on the
      differentiation of T lymphocyte subsets and the expression of specific
      transcription regulator T-bet/GATA binding protein 3 (GATA3). METHODS: A
      prospective double-blind study was conducted. Patients with CPB pulmonary repair
      of ventricular septal defect (observation group) or off-pump ligation of ductus
      arteriosus (control group) with 20 cases each in the 150th Military Hospital from
      February 2015 to February 2016 were enrolled. The blood sampled was collected on
      the time of before operation, at the end of CPB or operation, 4 hours after
      operation, and 24 hours after operation. T lymphocytes were isolated, the helper
      T cell 1 (Th1) specific transcription factor T-bet mRNA, helper T cell 2 (Th2)
      specific transcription factor GATA3 mRNA expression and cytokine gamma-interferon
      (IFN-gamma) mRNA, interleukin-4 (IL-4) mRNA expression were measured by Northern
      Blot. RESULTS: Compared with before operation, expression levels of T-bet mRNA
      [integral gray values: (1.39+/-0.52)*105 vs. (2.92+/-0.88)*105], IFN-gamma mRNA
      [integral gray values: (3.68+/-0.65)*105 vs. (6.10+/-0.93)*105] were decreased
      transiently at the end of CPB in the observation group (both P < 0.05), returned
      to preoperative levels at 24 hours after operation [integral gray values: (2.77+/
      0.74)*105, (6.22+/-1.25)*105, respectively, both P > 0.05]; expression levels of
      GATA3 mRNA [integral gray values: (4.96+/-0.88)*105 vs. (3.21+/-0.68)*105], IL-4
      mRNA [integral gray values: (3.52+/-1.13)*105 vs. (1.85+/-0.63)*105] were
      increased (both P < 0.05), recovered to the preoperative levels at 24 hours after
      operation [integral gray values: (3.11+/-0.51)*105, (1.93+/-0.84)*105,
      respectively, both P > 0.05]. There were no significant differences in the
      expressions of T-bet, GATA3, IFN-gamma and IL-4 mRNA in the control group at each
      time points (all P > 0.05). CONCLUSIONS: CPB causes the imbalance of Th1,
      Tc1/Th2, Tc2 and pro-inflammatory and anti-inflammatory reactions specially,
      which participate the complication occurrence after CPB. The changing of T
      bet/GATA3 may be the internal mechanism for these changes.

PMID- 29216946
TI  - [Diagnostic significance of urinary neutrophil gelatin enzyme-related lipid
      delivery protein and kidney injury molecule-1 in acute kidney injury after
      cardiac operation with cardiopulmonary bypass operation in children].
AB  - OBJECTIVE: To investigate the diagnostic value of urinary neutrophil gelatin
      enzyme-related lipid delivery protein (NGAL) and kidney injury molecule-1 (KIM-1)
      in the acute kidney injury (AKI) after cardiopulmonary bypass (CPB) operation in
      children with non-cyanotic congenital heart disease (CHD). METHODS: A
      retrospective analysis was conducted. 200 CPB undergoing cardiac surgery in
      children with non-cyanotic CHD admitted to Tianjin Children's Hospital from June
      2015 to May 2017 were enrolled. All patients were divided into AKI group and non
      AKI group within 48 hours after operation, and the two groups matched with age,
      sex, weight, basic complications, operation time and other factors. The
      differences in serum creatinine (SCr), urinary NGAL and KIM-1 [corrected for
      urinary creatinine (UCr)] between the two groups before and after operation were
      compared. The early diagnosis value of urinary NGAL and KIM-1 on AKI was analyzed
      by the receiver operating characteristic curve (ROC). RESULTS: There were 32
      patients with different degrees of AKI 48 hours post operation, and the incidence
      was 16.0%; 60 cases were enrolled in non-AKI group. Compared with non-AKI group,
      urinary NGAL at 2 hours after operation, urine KIM-1 at 4 hours after operation,
      and SCr at 10 hours after operation in AKI group were significantly increased,
      which decreased gradually after reaching peak at 6, 8, 24 hours respectively. It
      was shown by ROC curve analysis that the area under ROC curve (AUC) and 95%
      confidence interval (95%CI) of postoperative 2-hour urine NGAL, 4-hour urine KIM
      1 and 10-hour SCr for diagnosis of AKI were 0.940 (95%CI = 0.890-0.990), 0.939
      (95%CI = 0.891-0.986) and 0.959 (95%CI = 0.916-1.000) respectively. When the cut
      off value of postoperative 2-hour urine NGAL was 588.0 MUg/g, the sensitivity was
      87.5%, the specificity was 95.0%, the accuracy was 93.5%; when the cut-off value
      of postoperative 4-hour urine KIM-1 was 9.55 ng/mg, the sensitivity was 87.5%,
      the specificity was 91.7%, the accuracy was 90.2%; and when the cut-off value of
      postoperative 10-hour SCr was 61.90 MUmol/L, the sensitivity was 90.6%, the
      specificity was 95.0%, and the accuracy was 95.7%. CONCLUSIONS: Urine NGAL and
      KIM-1 can be used as biomarkers for early diagnosis of AKI after CPB for the non
      cyanotic CHD in children.

PMID- 29216947
TI  - [Effects of active abdominal compression-decompression CPR on oxygen metabolism
      and prognosis in patients with cardiac arrest].
AB  - OBJECTIVE: To analyze the effect of active abdominal compression-decompression
      cardiopulmonary resuscitation (AACD-CPR) and standard cardiopulmonary
      resuscitation (STD-CPR) on oxygen metabolism and prognosis of patient with
      cardiac arrest (CA), and to evaluate the treatment effect of AACD-CPR. METHODS:
      Patients with CA, CA time less than 30 minutes, and without STD-CPR and AACD-CPR
      contraindications admitted to the Zhengzhou People's Hospital from October 1st
      2015 to May 31st 2017 were enrolled. The patients were divided into STD-CPR group
      and AACD-CPR group according to random number table. All patients were given the
      same rescue measures, if required to give defibrillation; STD-CPR group was
      operated according to the 2015 American Heart Association (AHA) CPR guidelines;
      AACD-CPR group was recovered using abdominal lifting and compression
      cardiopulmonary resuscitation instrument. The oxygen metabolism, hemodynamic,
      arterial blood gas and prognostic indicators were recorded in the two groups
      during the resuscitation. RESULTS: A total of 69 cases, with STD-CPR group of 34
      cases and AACD-CPR group of 35 cases were enrolled finally. (1) The oxygen
      metabolism: during the recovery, compared with STD-CPR group, arterial blood
      oxygen content (CaO2), arterial-venous oxygen content difference (avDO2), the
      oxygen carrying capacity (DO2), oxygen consumption (VO2) in AACD-CPR group were
      significantly increased [CaO2 (mL/L): 156+/-15 vs. 142+/-19, avDO2 (mL/L): 83+/
      14 vs. 73+/-13, DO2 (mL/min): 248+/-51 vs. 208+/-54, VO2 (mL/min): 134+/-29 vs.
      118+/-32, all P < 0.05], but there were no significant differences in cardiac
      output (CO) and mixed venous oxygen content (CvO2). (2) Hemodynamic and arterial
      blood gas: there were no significant differences in the base values of the heart
      rate (HR), mean arterial pressure (MAP), pH value, pulse oxygen saturation
      (SpO2), arterial oxygen pressure (PaO2), arterial partial pressure of carbon
      dioxide (PaCO2), and blood lactate (Lac) between two groups. In the recovery
      process, MAP, pH value, SpO2, PaO2 of two groups were increased, while PaCO2 and
      Lac were decreased. Except MAP of STD-CPR group was slightly higher than AACD-CPR
      group, the change tendency of AACD-CPR group was more obvious in each index
      obviously [pH value difference: 0.10+/-0.15 vs. 0.02+/-0.13, SpO2 difference:
      0.311+/-0.255 vs. 0.159+/-0.232, PaO2 difference (mmHg, 1 mmHg = 0.133 kPa):
      12.96+/-21.84 vs. 3.01+/-13.56, PaCO2 difference (mmHg): -9.91+/-11.17 vs. 
      3.52+/-13.87, Lac value difference (mmol/L): -0.64+/-0.61 vs. -0.31+/-0.58, all P
      < 0.05]. (3) Prognosis: compared with STD-CPR group, the restoration of
      spontaneous circulation (ROSC) rate in AACD-CPR group was slightly increased
      (22.9% vs. 8.8%, P > 0.05), but the ROSC time in AACD-CPR group was significantly
      shortened (minutes: 9.59+/-2.67 vs. 11.83+/-3.05, P < 0.01), nerve function
      defect score (NDS) was significantly decreased at 1, 2 weeks (26.45+/-6.42 vs.
      30.73+/-7.38, 19.25+/-6.27 vs. 22.64+/-5.63, both P < 0.05), and the 2-week
      survival was slightly increased (17.1% vs. 5.9%, P > 0.05). CONCLUSIONS: AACD-CPR
      is similar to STD-CPR in improving hemodynamics of CA patients, but has advantage
      in the blood oxygen supply for tissues and organs, and the neurological function
      prognosis is better.

PMID- 29216948
TI  - [Tea polyphenols down-regulate JNK phosphorylation to inhibit neuron apoptosis in
      rats with cardiac arrest].
AB  - OBJECTIVE: To study the effect of tea polyphenols (TP) on c-Jun N-terminal kinase
      1/2 (JNK1/2) phosphorylation and cell apoptosis in brain tissues in rats with
      cardiac arrest (CA) following cardiopulmonary resuscitation (CPR). METHODS:
      Healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n =
      6), CA group (n = 12), and TP group (n = 12). The rats in CA and TP groups were
      induced ventricular fibrillation (VF) via esophagus stimulation with alternating
      current. Five minutes after CA, CPR was performed. Once restoration of
      spontaneous circulation (ROSC) was gained, normal saline (NS) and TP were
      injected intravenously in CA and TP groups with 10 mg/kg, respectively. Cortex of
      6 rats in each group was harvested at 12 hours and 72 hours after ROSC. Cortex of
      sham group was harvested at 72 hours after operation without VF induction. The
      expressions of phosphorylated JNK1/2 (p-JNK1/2), JNK1/2, caspase-3, Bax and Bcl-2
      were measured by Western Blot. Cell apoptosis was detected by TdT-mediated dUTP
      nick end labeling (TUNEL), and p-JNK/TUNEL double positive cells were detected by
      fluorescence double staining. RESULTS: Compared with sham group, the expressions
      of p-JNK, caspase-3 and Bax were increased, the expression of Bcl-2 was declined,
      and the apoptotic cells were significantly increased at 72 hours after ROSC in CA
      group. Compared with CA group, the phosphorylation of JNK was significantly
      declined at 12 hours and 72 hours after ROSC in TP group (the ratio of p-JNK1/2
      and JNK1/2: 3.200+/-0.060 vs. 5.700+/-0.210, 1.400+/-0.060 vs. 5.400+/-0.090,
      both P < 0.05), the expressions of caspase-3 and Bax were decreased [caspase-3
      (gray value): 42.00+/-5.23 vs. 54.00+/-7.84, 38.74+/-4.60 vs. 58.68+/-7.19; Bax
      (gray value): 38.04+/-6.21 vs. 68.76+/-6.08, 58.84+/-7.99 vs. 70.03+/-7.36, all P
      < 0.05], the expression of Bcl-2 was increased (gray value: 37.36+/-3.11 vs.
      28.47+/-7.46, 48.78+/-6.55 vs. 29.54+/-3.13, both P < 0.05); the cell apoptosis
      rate was reduced at 72 hours [(31.14+/-4.51)% vs. (45.87+/-3.95)%, P < 0.01], and
      p-JNK/TUNEL double positive cells/TUNEL cells ratio was significantly decreased
      (10.00+/-0.85 vs. 52.70+/-3.05, P < 0.01). CONCLUSIONS: The inhibition of neuron
      apoptosis caused by TP after CPR in rats with CA is related to the inhibition of
      JNK1/2 phosphorylation.

PMID- 29216949
TI  - [Effects of N-butylphthalide on the expressions of calpain 1 and CaMK II in
      hippocampus in rats with acute severe carbon monoxide poisoning].
AB  - OBJECTIVE: To investigate the effects of N-butylphthalide (NBP) on cognitive
      function in acute severe carbon monoxide (CO) poisoning rats and its mechanism.
      METHODS: 120 health Sprague-Dawley (SD) rats were randomly divided into three
      groups (n = 40): normal control group (NC group), CO poisoning group (CO group)
      and NBP treatment group (NBP group). The acute severe CO poisoning model was
      established in a hyperbaric oxygen chamber by intoxicated with 1 000 *10-6 CO for
      40 minutes, followed with 3 000 *10-6 CO for another 20 minutes, and then
      received hyperbaric oxygen therapy 1.5 hours once a day until sacrificed. Rats in
      NBP group were administered orally NBP 60 mg/kg for 2 times daily until death. NC
      group and CO group were treated with equal amount of pure olive oil. Four rats in
      each group were taken from 1, 3, 7, 14, 30 days after model setup, respectively.
      The cognitive function score was assessed by Morris water maze test. The changes
      in ultrastructure of hippocampus were observed under transmission electron
      microscope. The expressions of calpain 1 and Ca2+/calmodulin dependent protein
      kinase II (CaMK II) in hippocampus of brain tissue were detected by
      immunofluorescence staining, and the localization of the two target proteins in
      neurons was observed by immunofluorescence double staining. RESULTS: Compared
      with NC group, the escape latency at 1 day after poisoning in CO group was
      significantly prolonged (s: 55.6+/-3.2 vs. 44.5+/-3.5, P < 0.05), and the times
      of the platform crossing was significantly decreased (times: 1.3+/-0.8 vs. 6.6+/
      1.2, P < 0.05); the ultrastructure of hippocampus was obviously injured; the
      protein expressions of calpain 1 and CaMK II in brain tissue were significantly
      increased at 1 day after CO poisoning [calpain 1 (A value): 41.24+/-5.21 vs.
      6.44+/-1.13, CaMK II (A value): 56.19+/-5.04 vs. 9.84+/-1.53, both P < 0.05], and
      the protein expression of calpain 1 reached the peak at 3 days (A value: 59.34+/
      6.11), the protein expression of CaMK II reached the peak at 1 day (A value:
      56.19+/-5.04). Compared with CO group, the cognitive function was significantly
      improved in NBP group in the late stage of poisoning [7-30 days, escape latency
      (s): 40.3+/-1.9 vs. 49.1+/-3.1 at 7 days, 30.1+/-2.9 vs. 39.4+/-3.1 at 30 days;
      times of the platform crossing (times): 2.8+/-1.0 vs. 1.0+/-0.9 at 14 days, 3.2+/
      0.8 vs. 1.0+/-0.9 at 30 days, all P < 0.05]; the degree of injury of hippocampal
      neuron was relatively slight; the protein expression of calpain 1 in brain tissue
      was significantly decreased from 3 days after CO poisoning (A value: 39.63+/-3.03
      vs. 59.34+/-6.11, P < 0.05), and the protein expression of CaMK II was
      significantly decreased from 1 day after CO poisoning (A value: 42.22+/-3.84 vs.
      56.19+/-5.04, P < 0.05). Immunofluorescence double staining suggested that
      calpain 1 and CaMK II protein could not only coexist in the same cell, but also
      could be expressed separately in different cells. Linear regression analysis
      showed that the expression of calpain 1 and CaMK II was positively correlated (R
      2 = 0.852, P = 0.002). CONCLUSIONS: NBP treatment could maintain ultrastructure
      integrity of hippocampus, balance the expression levels of calpain 1 and CaMK II
      proteins, and significantly improve cognitive impairment induced by CO poisoning,
      thus play a protective role against hippocampus damage in rats with acute severe
      CO poisoning.

PMID- 29216950
TI  - [Effect of early enteral nutrition standardized treatment on blood glucose and
      prognosis in acute respiratory distress syndrome patients with mechanical
      ventilation].
AB  - OBJECTIVE: To study the effect of early entreat nutrition (EN) standardized
      treatment on optimization of blood glucose control and prognosis in acute
      respiratory distress syndrome (ARDS) patients with mechanical ventilation (MV).
      METHODS: Forty-two patients with MV of ARDS admitted to Huzhou First Municipal
      People's Hospital from April 2015 to March 2017 were enrolled. April 1st, 2016
      was taken as the time node, the patients treated from April 1st, 2015 to March
      31st, 2016 were assigned in the control group (n = 20), while the patients
      treated from April 1st, 2016 to March 31st, 2017 were included in the
      experimental group (n = 22). The patients in experimental group were given
      conventional treatment, in 24-48 hours after admission gastrointestinal
      decompression was stopped and early EN was begun through a nasointestinal tube;
      the patients in control group received conventional treatment and routine EN
      (given 48 hours after admission). The differences in nutritional support indexes,
      the blood glucose variability indexes and the prognostic related indicators were
      compared between the two groups. RESULTS: Compared with the control group, the
      initiation time for EN tolerance, first defecation time, time of reaching target
      feeding amount were significantly earlier in the early EN standardized treatment
      process management [time of initial EN tolerance (hours): 106.82+/-42.84 vs.
      157.29+/-56.76, first defecation time (hours): 71.29+/-23.43 vs. 104.69+/-26.94,
      time of reaching target feeding amount (days): 6.24+/-1.25 vs. 9.86+/-2.36], the
      proportions of EN/EN+parenteral nutrition (PN) and the nasointestinal tube
      feeding reaching the standard on 7 days in experimental group were significantly
      increased [the proportion of EN/EN+PN: 98.69% vs. 78.69%, the nasointestinal tube
      feeding reaching standard: 68.18% (15/22) vs. 45.00% (9/20)], average level of
      blood glucose (GLUave), maximum value of blood glucose (GLUmax), standard
      deviation of blood glucose (GLUsd), coefficient of variation of blood glucose
      (GLUcv), hyperglycemia incidence, incidence of multiple organ dysfunction
      syndrome (MODS), 28-day mortality were significantly decreased [GLUave (mmol/L):
      9.4+/-2.6 vs. 11.5+/-3.9, GLUmax (mmol/L): 14.19+/-2.36 vs. 16.26+/-4.89, GLUsd
      (mmol/L): 4.86+/-1.27 vs. 6.87+/-2.46, GLUcv: (49.86+/-6.32)% vs. (59.95+/
      5.81)%, hyperglycemia incidence: 59.09% (13/22) vs. 80.00% (16/20), incidence of
      MODS: 59.09% (13/22) vs. 80.00% (16/20), 28-day mortality: 36.36% (8/22) vs.
      45.00% (9/20)], minimum value of blood glucose (GLUmin) was significantly
      increased (mmol/L: 5.86+/-2.32 vs. 4.18+/-1.86), invasive MV time was
      significantly shorted (hours: 156.82+/-26.84 vs. 169.93+/-32.34) with
      statistically significant differences (all P < 0.05). Early EN could also improve
      the patient's pulmonary oxygenation function. Since 9 days of disease course, the
      oxygenation index (PaO2/FiO2) in the experimental group was significantly higher
      than that of the control group [mmHg (1 mmHg = 0.133 kPa): 256.97+/-18.63 vs.
      239.82+/-21.72, P = 0.068], but there was no significant difference in the length
      of ICU stay (days: 13.9+/-3.6 vs. 14.8+/-3.4, P > 0.05). CONCLUSIONS: The early
      EN standardized treatment process management can improve the nutritional status,
      decrease blood sugar fluctuations, and further benefit the improvement of the
      prognosis of ARDS patients with MV.

PMID- 29216951
TI  - [Design and application of portable rescue vehicle].
AB  - OBJECTIVE: The disease of critically ill patients was with rapid changes, and at
      any time faced the risk of emergency. The current commonly used rescue vehicles
      were larger and bulky implementation, which were not conducive to the operation,
      therefore the design of a portable rescue vehicle was needed. This new type of
      rescue vehicle is multi-layer folding structure, with small footprint, large
      storage space, so a variety of first aid things can be classified and put, easy
      to be cleaned and disinfected. In the rescue process, the portable rescue
      vehicles can be placed in the required position; box of various emergency items
      can be found at a glance with easy access; the height of the infusion stand can
      adjust freely according to the user height; the rescue vehicle handle can be easy
      to pull and adjust accord with human body mechanics principle. The portable
      rescue vehicle facilitates the operation of medical staff, and is worthy of
      clinical application.

PMID- 29216952
TI  - [Sepsis-induced cardiomyopathy complicated with cardiogenic shock patients
      supported with extracorporeal membrane oxygenation].
AB  - OBJECTIVE: Sepsis-induced cardiomyopathy is a reversible myocardial dysfunction
      due to sepsis, which may be severe enough to complicate cardiogenic shock, and
      without effective drug and with high mortality during the acute phase. A case of
      sepsis-induced cardiomyopathy complicated with cardiogenic shock was treated in
      the intensive care unit (ICU) of Shunde Hospital Southern Medical University. A
      37 years old female patient was admitted because she had suffered repeated fever
      for 5 days, chest tightness and abdominal pain for 3 days. At the same time,
      there were severe cardiac depression and abdominal infection, which could be
      explained by the monismtheory of sepsis cardiomyopathy.The cardiogenic shock
      patient was not improved after antibiotic therapy and hemodynamic support,
      extracorporeal membrane oxygenation (ECMO) support was prescribed. The
      circulation failure was smoothly got through with ECMO and was transfer from ICU
      to ordinary ward. Computed tomographic angiography (CTA) of abdominal aorta and
      colonoscopy indicated lesions of small intestine. The diagnosis of infection and
      bleeding in ileum diverticulum was confirmed during the operation and the lesions
      was removed. She recovered and was discharged 1 week after operation. Through the
      case review, we aim to improve the awareness of sepsis-induced cardiomyopathy and
      the value of ECMO support in cardiogenic shock.

PMID- 29216953
TI  - [Significance of heparin in the treatment of patients with sepsis].
AB  - OBJECTIVE: The latest definition of sepsis (Sepsis-3) is the life-threatening
      organ dysfunction due to overreaction of immune system caused by infection. The
      situation can develop into multiple organ dysfunction syndromes (MODS). In the
      pathological process of pathogen invasion, a large number of inflammatory factors
      directly damage organ function, while dysfunction of coagulation system is also
      involved in this process. With the overreaction of inflammation, disseminated
      intravascular coagulation (DIC) occurred, which further exacerbated organ damage.
      As excessive inflammation and coagulation disorders are mutually reinforced, the
      clearance of pathogenic microorganisms and the control of inflammatory reactions
      cannot effectively improve the sepsis caused by MODS. As a clinically readily
      available anticoagulant, heparin is widely used in a variety of severe situations
      caused by DIC, thromboembolic disease and some invasive procedure for
      anticoagulant treatment. In recent years, domestic and foreign studies have found
      that heparin has a certain anti-inflammatory effect, which can reduce the
      incidence of DIC, improve sepsis patients with microcirculation and MODS, reduce
      28-day mortality. However, there is controversy in its effectiveness and safety.
      Therefore, the application of heparin in the treatment of sepsis need to be
      further defined and discussed.

PMID- 29216954
TI  - [Advances in risk factors of Klebsiella pneumoniae carbapenemases-producing
      Klebsiella pneumoniae infection or colonization and its treatment strategies].
AB  - OBJECTIVE: Klebsiella pneumoniae carbapenemases-producing Klebsiella pneumoniae
      (KPC-Kp) has caused a global public health crisis, and the severity of its
      infection is associated with high mortality in hospitalized patients. Therefore,
      the KPC-Kp prevention methods and the corresponding treatment strategy
      exploration are imminent. The risk factors and the treatment progress of KPC-Kp
      colonization or infection are reviewed in this paper to explore corresponding
      preventive measures and treatment strategies for clinical prevention and
      treatment.

PMID- 29216955
TI  - Combined Toxicity of an Environmental Remediation Residue, Magnetite Fe3O4
      Nanoparticles/Cr(VI) Adduct.
AB  - OBJECTIVE: This paper aims to elucidate the combined toxicity of magnetite
      nanoparticles/Chromium [MNPs/Cr(VI)] adducts. METHODS: The HEK293 cell was
      exposed to either Cr(VI) or MNPs, or their adducts MNPs/Cr(VI). The cytotoxicity
      was evaluated by assessing the cell viability, apoptosis, oxidative stress
      induction, and cellular uptake. RESULTS: The toxicity of formed adducts is
      significantly reduced when compared to Cr(VI) anions. We found that the cellular
      uptake of MNPs/Cr(VI) adduct was rare, only few particles were endocytosed from
      the extracellular fluid and not accumulated in the cell nucleus. On the other
      hand, the Cr(VI) anions entered cells, generated oxidative stress, induced cell
      apoptosis, and caused cytotoxicity. CONCLUSION: The results showed minor effects
      of the nanoadducts on the tested cells and supported that magnetite nanoparticles
      could be implemented in the wastewater treatment process in which advantageous
      properties outweigh the risks.

PMID- 29216956
TI  - Increased PIT1 and PIT2 Expression in Streptozotocin (STZ)-induced Diabetic Mice
      Contributes to Uptake of iAs(V).
AB  - OBJECTIVE: This study aimed to investigate the susceptibility of mice with
      streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent
      inorganic arsenic (iAsV) and the possible molecular mechanism. METHODS: TIDM was
      induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg
      Na2HAsO4.12H2O by intragastric administration. Then, the concentrations of
      arsenic in various tissues were measured by atomic fluorescence spectrometry. The
      gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and
      their protein levels were detected by Western blotting in mouse heart, kidney,
      and liver tissues. RESULTS: The concentrations of arsenic in STZ-induced TIDM
      mouse tissues were higher at 2 h after intragastric administration of
      Na2HAsO4.12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which
      play a role in the uptake of iAsV, were upregulated in the livers and hearts of
      TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation
      of Pit1 and Pit2 expression could be reversed by insulin treatment. CONCLUSION:
      The increased uptake of iAsV in TIDM mouse tissues may be associated with
      increased PIT1 and/or PIT2 expression.

PMID- 29216957
TI  - Handgrip Strength as a Predictor of Nutritional Status in Chinese Elderly
      Inpatients at Hospital Admission.
AB  - OBJECTIVE: To assess nutritional status and define gender- and age-specific
      handgrip strength (HGS) cut-point values for malnutrition or nutritional risk in
      elderly inpatients. METHODS: A cross-sectional study of 1,343 elderly inpatients
      was conducted in the Chinese PLA General Hospital. Nutrition Risk Screening (NRS
      2002) and Subjective Global Assessment (SGA) were administered. Anthropometric
      measurements and blood biochemical indicators were obtained using standard
      techniques. The gender- and age-specific receiver operating characteristic (ROC)
      curves were constructed to evaluate the HGS for nutritional status by SGA and NRS
      2002. Sensitivity, specificity, and areas under the curves (AUCs) were
      calculated. RESULTS: According to NRS 2002 and SGA, 63.81% of elderly inpatients
      were at nutritional risk and 28.22% were malnourished. Patients with higher HGS
      had an independently decreased risk of malnutrition and nutritional risk. The
      AUCs varied between 0.670 and 0.761. According to NRS 2002, the optimal HGS cut
      points were 27.5 kg (65-74 years) and 21.0 kg (75-90 years) for men and 17.0 kg
      (65-74 years) and 14.6 kg (75-90 years) for women. According to SGA, the optimal
      HGS cut-points were 24.9 kg (65-74 years) and 20.8 kg (75-90 years) for men and
      15.2 kg (65-74 years) and 13.5 kg (75-90 years) for women. CONCLUSION: Elderly
      inpatients had increased incidence of malnutrition or nutritional risk. HGS cut
      points can be used for assessing nutritional status in elderly inpatients at
      hospital admission in China.

PMID- 29216958
TI  - Investigation of Extracts from Tunisian Ethnomedicinal Plants as Antioxidants,
      Cytotoxins, and Antimicrobials.
AB  - OBJECTIVE: To determine the medicinal potential of various plants and their parts
      extracted with different solvents. METHODS: The total phenolic content of
      acetonitrile/water (60%-40%) (ACN/W) and aqueous (W) extract fractions was
      determined by high-performance liquid chromatography (HPLC), and terpenic
      compounds were detected by gas chromatography/mass spectrometry (GC/MS).
      Antioxidant activity of the samples was evaluated using 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay and beta-carotene bleaching method. Cell viability
      was investigated by thiazolyl blue tetrazolium bromide [3-(4,5-dimethylthiazol)-2
      yl 2,5-diphenyltetrazolium bromide] (MTT) assay. The mechanisms involved in
      cytotoxic activity were investigated in a murine macrophage cell line (RAW 264.7)
      and cancer lines. RESULTS: Our findings show that 11 plant species exhibited
      biological activity. In addition, moderate antibacterial activity was reported
      against one or more of the tested bacterial strains at two concentrations: 300
      MUg and 3 mg/disc. Furthermore, our data reveal that among all plants
      investigated, some extract and hydrophobic fractions were potent scavengers of
      the DPPH radical (6.78 MUg/mL < EC50 < 8.55 MUg/mL). Taken together, our results
      show that Nerium oleander (NOACN/W) and Pituranthos tortuosus (PTACN/W) were
      highly cytotoxic against RAW 264.7 cells with IC80 values of 0.36, and 1.55
      MUg/mL, respectively. In contrast, murine macrophage cell lines had low growth
      and were significantly sensitive to water extracts of Thymus hirtus sp.
      algeriensis (THW), Lavandula multifida (LMW), and ACN/W extract of Erica
      multiflora (EMACN/W) at doses > 400, 47.20, and 116.74 MUg/mL, respectively. The
      current work demonstrates that RAW 264.7 cell proliferation was inhibited by
      samples in a dose-dependent manner. CONCLUSION: Our findings, validated through
      free radical scavenging activity, agar diffusion assay, and cytotoxicity of
      essential oils towards cancer cells, show that ethnomedicinal plants used in this
      work have a novel application as a tumor suppressor.

PMID- 29216959
TI  - An Investigation of the First Case of Human Rabies Caused by a Fox in China in
      May 2016.
AB  - This study assesses the causes and prevention measures of rabies through
      epidemiological investigation and analysis. A field epidemiological survey was
      conducted to investigate a case of rabies by fox bite. The onset of symptoms
      began 50 days after the bite. The patient did not receive standard treatment,
      rabies vaccination, or rabies immunoglobulin injection. The fox was killed on the
      spot. Saliva and pre-death blood samples were collected at different periods, and
      only blood RT-PCR tests yielded positive results. Wild fox bite is a major risk
      factor of rabies infection in Xinjiang Province, China.

PMID- 29216960
TI  - Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region,
      China, 2018.
AB  - Population-based cancer registration data were collected to estimate the cancer
      incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used
      the 2011-2013 data to predict the number of new cases and deaths in 2018 and the
      2003-2013 data to analyze trends in cancer incidence and mortality. The goal is
      to enable cancer prevention and control directions. Our results indicated that
      stomach cancer is the most common cancer. For all cancers combined, the incidence
      and mortality rates showed significantly increasing trends (+2.63% per year; P <
      0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer
      burden among the population of this area. Cancer screening and prevention should
      be performed after an epidemiological study of the cause of the cancer is
      completed.

PMID- 29216961
TI  - Identification and Validation of Candidate Radiation-responsive Genes for Human
      Biodosimetr.
AB  - The aim of the present study is to analyze the global research trend of radiation
      responsive genes and identify the highly reproducible radiation-responsive genes.
      Bibliometric methods were applied to analyze the global research trend of
      radiation-responsive genes. We found 79 publications on radiation-responsive
      genes from 2000 to 2017. A total of 35 highly reproducible radiation-responsive
      genes were identified. Most genes are involved in response to DNA damage, cell
      proliferation, cell cycle regulation, and DNA repair. The p53 signal pathway was
      the top enriched pathway. The expression levels of 18 genes in human B
      lymphoblastoid cell line (AHH-1) cells were significantly up-regulated in a dose
      dependent manner at 24 h after exposure to 0-5 Gy 60Co gamma-ray irradiation. Our
      results indicate that developing a gene expression panel with the 35 high
      reproducibility radiation-responsive genes may be necessary for qualitative and
      quantitative assessment after exposure.

PMID- 29216962
TI  - Lead Exposure and Oxidative Stress in Coal Miners.
AB  - We aimed to investigate the short-term correlation between blood lead levels and
      oxidative stress generation in coal miners. The study involved 94 male coal
      miners from the Velenje Coal mine, arranged into four groups: three groups
      according to the number of consecutive working days, and a fourth control group.
      Miners who worked for three consecutive days had higher blood levels of lead and
      8-isoprostane than the control group (P < 0.001). Correlation between lead and 8
      isoprostane was of medium strength (r = 0.512, P < 0.001). Short-term lead
      environmental exposure can potentially harmful and should be considered when
      formulating improvements in working processes.

PMID- 29216963
TI  - Psychophysiological Effects of Bamboo Plants on Adults.
AB  - The present study was conducted to clarify the psychophysiological relaxation
      effects of viewing bamboo on university students. Forty healthy Chinese
      participants enrolled in this study to clarify the psychophysiological relaxation
      effects of viewing bamboo. The effects of visual stimulation using a pot both
      with and without a bamboo were recorded by measuring the student's blood
      pressure, EEG and STAI. We observed that viewing bamboo plants resulted in
      significantly lower systolic (female, P < 0.001; male, P < 0.001; P < 0.05) and
      diastolic (female, P < 0.001; male, P < 0.001; P < 0.05) blood pressures, but no
      changes in the pulse rate (female, P = 0.09; male, P = 0.07; P > 0.05) were
      observed. The results of the EEG analysis indicated brainwave variation (all P <
      0.05) and lower anxiety scores (P < 0.01) after 3 min of viewing bamboo compared
      with the control. These findings indicate that visual stimulation with bamboo
      plants induced psychophysiological relaxation effects on adults.

PMID- 29216964
TI  - Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with
      That in Other Tissues of Rats by Acute Toxicity Test.
AB  - Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1
      mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total
      relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system
      (thighbone, knee joints, and costal cartilage) were significantly higher than
      those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of
      T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage)
      were also significantly higher than those in the heart, liver, and kidneys. The
      rats administered T-2 toxin showed rapid metabolism compared with that in rats
      administered HT-2 toxin, and the metabolic conversion rates in the different
      tissues were 68.20%-90.70%.

PMID- 29216965
TI  - A Tiny RNA Molecule with a Big Impact on Type 2 Diabetes Mellitus Susceptibility.

PMID- 29216967
TI  - Caring for transgender people: looking beyond the hype.
AB  - This special issue of Sexual Health presents a collection of articles that
      addresses issues facing transgender individuals that are particularly
      challenging. Issues covered range from sexual health education in schools, the
      need for accurate epidemiological measurements, the perils of inaccurate
      diagnostic labels of transgender children, legal issues, the disproportionately
      high prevalence of HIV and sexually transmissible infections (STIs), and the role
      of primary care. We need to think critically, constructively and compassionately
      about transgender people. Particularly, we must look beyond the hype and
      objectively consider the evidence, without forgetting the people who are trying
      to cope with feelings that may be causing them great distress.

PMID- 29216968
TI  - Gender trouble: The World Health Organization, the International Statistical
      Classification of Diseases and Related Health Problems (ICD)-11 and the trans
      kids.
AB  - The World Health Organization (WHO) is revising its diagnostic manual, the
      International Statistical Classification of Diseases and Related Health Problems
      (ICD). At the time of writing, and based on recommendations from its ICD Working
      Group on Sexual Disorders and Sexual Health, WHO is proposing a new ICD chapter
      titled Conditions Related to Sexual Health, and that the gender incongruence
      diagnoses (replacements for the gender identity disorder diagnoses used in ICD
      10) should be placed in that chapter. WHO is proposing that there should be a
      Gender incongruence of childhood (GIC) diagnosis for children below the age of
      puberty. This last proposal has come under fire. Trans community groups, as well
      as many healthcare professionals and others working for transgender health and
      wellbeing, have criticised the proposal on the grounds that the pathologisation
      of gender diversity at such a young age is inappropriate, unnecessary, harmful
      and inconsistent with WHO's approach in regard to other aspects of development in
      childhood and youth. Counter proposals have been offered that do not pathologise
      gender diversity and instead make use of Z codes to frame and document any
      contacts that young gender diverse children may have with health services. The
      author draws on his involvement in the ICD revision process, both as a member of
      the aforementioned WHO Working Group and as one of its critics, to put the case
      against the GIC proposal, and to recommend an alternative approach for ICD in
      addressing the needs of gender diverse children.

PMID- 29216969
TI  - Legal issues for transgender people: a review of persistent threats.
AB  - Background The legal status of transgender (trans) people is in constant flux.
      Over the past 70 years, gradually increasing transgender visibility, national and
      global advocacy, and, more recently, widespread Internet access, communication,
      and broadening support from allies, have all contributed to successful campaigns
      that have improved transgender lives and legitimised transgender. Still,
      traumatic interactions with the legal system or policing agencies remain
      plentiful. This is a very general overview of the most common legal issues
      confronting trans people. It aims to inform medical and mental health providers
      about the trepidation with which their patients and clients must engage legal
      systems, and the scope of their concerns, which ultimately affect their health.
      This review relies upon reports generated by advocacy organisations based on
      population surveys in several countries, the projects undertaken by legal and
      human rights advocacy groups, the topics most frequently discussed in academic
      texts examining transgender legal issues, and draws upon the author's personal
      advocacy experience. The most complicated and persistent issues are identity
      recognition, family law and relationship issues, adverse discrimination and anti
      transgender violence and its aftermath. Criminal law, almost universally, treats
      trans people according to the lowest common denominator, their genital status,
      which supposedly supports expediency and "safety". Global legal and human rights
      efforts remain desperately needed to lift transgender people from the margins of
      society and provide them with equal opportunities to lead healthy and fulfilling
      lives. Access to appropriate and meaningful health care is a crucial element
      necessary to affirm the humanity of any person.

PMID- 29216970
TI  - Current research gaps: a global systematic review of HIV and sexually
      transmissible infections among transgender populations.
AB  - Transgender populations are heavily burdened by HIV and other sexually
      transmissible infections (STIs). However, data on co-infection with HIV and STIs
      among transgender people are limited. A systematic review was conducted of peer
      reviewed articles and conference abstracts between January 2010 and November 2015
      that focussed on HIV and STI infections among transgender populations globally.
      The literature was synthesised and opportunities for improving health research
      were commented on. Few studies reported HIV-STI co-infection (n=4), while the
      majority of studies reported HIV and STI infections separately (n=23). Most
      studies were conducted outside of the USA (n=19), and all but one of these
      studies reported data on transgender women only. Among USA-based studies (n=8),
      several reported data on both transgender men and transgender women (n=3),
      whereas other studies reported exclusively on transgender men (n=1) or
      transgender women (n=4). Understanding HIV and STIs among transgender people
      requires research that simultaneously considers multilevel drivers of
      vulnerabilities. More data are needed on how the interaction of individual
      determinants, including biological risks of transmission, programmatic
      determinants such as service-delivery models and policy-level determinants
      including institutionalised stigma in healthcare settings, influence the HIV- and
      STI-related outcomes of transgender populations. Leveraging the knowledge of
      transgender-specific determinants of HIV and STIs should guide the content and
      approaches to future HIV and STI prevention and treatment efforts.

PMID- 29216971
TI  - Evaluation of the ability of arsenic species to traverse cell membranes by simple
      diffusion using octanol-water and liposome-water partition coefficients.
AB  - Arsenic metabolism in living organisms is dependent on the ability of different
      arsenic species to traverse biological membranes. Simple diffusion provides an
      alternative influx and efflux route to mediated transport mechanisms that can
      increase the amount of arsenic available for metabolism in cells. Using octanol
      water and liposome-water partition coefficients, the ability of arsenous acid,
      arsenate, methylarsonate, dimethylarsinate, thio-methylarsonate, thio
      dimethylarsinic acid, arsenotriglutathione and monomethylarsonic diglutathione to
      diffuse through the lipid bilayer of cell membranes was investigated. Molecular
      modelling of arsenic species was used to explain the results. All arsenic species
      with the exception of arsenate, methylarsonate and thio-methylarsonate were able
      to diffuse through the lipid bilayer of liposomes, with liposome-water partition
      coefficients between 0.04 and 0.13. Trivalent arsenic species and thio
      pentavalent arsenic species showed higher partition coefficients, suggesting that
      they can easily traverse cell membranes by passive simple diffusion. Given the
      higher toxicity of these species compared to oxo-pentavalent arsenic species,
      this study provides evidence supporting the risk associated with human exposure
      to trivalent and thio-arsenic species.

PMID- 29216972
TI  - Predatory publishing is everyone's concern.

PMID- 29216973
TI  - May you live in interesting times!

PMID- 29216974
TI  - Position statement: Full practice authority for advanced practice registered
      nurses is necessary to transform primary care.

PMID- 29216975
TI  - Position statement: Reducing fatigue associated with sleep deficiency and work
      hours in nurses.

PMID- 29216976
TI  - IVUS-Guided Versus OCT-Guided Coronary Stent Implantation: A Critical Appraisal.
AB  - Procedural guidance with intravascular ultrasound (IVUS) imaging improves the
      clinical outcomes of patients undergoing percutaneous coronary intervention (PCI)
      by: 1) informing the necessity for lesion preparation; 2) directing appropriate
      stent sizing to maximize the final stent area and minimize geographic miss; 3)
      selecting the optimal stent length to cover residual disease adjacent to the
      lesion, thus minimizing geographic miss; 4) guiding optimal stent expansion; 5)
      identifying acute complications (edge dissection, stent malapposition, tissue
      protrusion); and 6) clarifying the mechanism of late stent failure (stent
      thrombosis, neointimal hyperplasia, stent underexpansion or fracture, or
      neoatherosclerosis). Optical coherence tomography (OCT) provides similar
      information to IVUS (with some important differences), also potentially improving
      acute and long-term patient outcomes compared to angiography-guided PCI. The
      purpose of this review is to describe the similarities and differences between
      IVUS and OCT technologies, and to highlight the evidence supporting their utility
      to improve PCI outcomes.

PMID- 29216977
TI  - Noninvasive Cardiac Imaging and the Prediction of Heart Failure Progression in
      Preclinical Stage A/B Subjects.
AB  - Heart failure (HF) continues to grow as a cause of morbidity and mortality in our
      community and presents a significant public health problem, predominantly in
      individuals >=65 years of age. Early intervention in asymptomatic HF subjects
      (Stage A/B) at risk of progression to symptomatic HF (Stage C/D) may provide an
      opportunity to halt this epidemic. The ability of cardiac imaging to assess
      cardiac structure and function permits early identification of those at increased
      risk of developing symptomatic HF. Systolic, diastolic, and structural left
      ventricular parameters each predict symptomatic HF, but no single parameter has
      sufficient sensitivity for screening to identify individuals with Stage A/B HF
      who are at increased risk of disease progression. Transthoracic echocardiography
      (TTE) has the advantage over other imaging modalities in being able to measure
      systolic, diastolic, and structural left ventricular parameters, and it
      identified at least 1 abnormal parameter in >50% of individuals with Stage A/B HF
      >=65 years of age. Moreover, identification of at least 1 abnormality according
      to TTE in individuals with Stage A/B HF >=65 years of age had 72% to 82%
      sensitivity for detection of those who subsequently developed symptomatic HF.
      Therefore, a case can be made for cardiac imaging by using TTE for community
      dwelling populations with Stage A/B HF >=65 years of age to identify those with
      increased risk of symptomatic HF who can be offered preventative therapies.
      Further studies are required to determine the best strategy for identifying the
      risk of symptomatic HF in younger individuals.

PMID- 29216978
TI  - Female Athlete's Heart: Appropriate Scaling to Body Size May Resolve Diagnostic
      Conundrums.

PMID- 29216979
TI  - The Authors Reply.

PMID- 29216980
TI  - The Challenges of Diagnosing Cardiac Sarcoidosis.

PMID- 29216981
TI  - Correction.

PMID- 29216982
TI  - Is a DASH of Salt All We Need?

PMID- 29216984
TI  - Atrial Myocardial Infarction: A Neglected Stalker in Coronary Patients.

PMID- 29216983
TI  - Atrial Infarction and Ischemic Mitral Regurgitation Contribute to Post-MI
      Remodeling of the Left Atrium.
AB  - BACKGROUND: Left atrial (LA) remodeling after an acute myocardial infarction (MI)
      is poorly characterized regarding its determinants or its effect on ischemic
      mitral regurgitation (MR) development. OBJECTIVES: The purpose of this study was:
      1) to compare LA structural remodeling in experimental MI swine models
      recapitulating the effects of left ventricular (LV) dysfunction, ischemic MR, and
      left atrial infarction (LAI); and 2) to analyze how LA remodeling influences
      ischemic MR development. METHODS: Three models of MI were generated: 1) proximal
      left circumflex (LCx) coronary artery occlusion involving the LA branch (LAI
      group); 2) proximal LCx occlusion not involving the LA branch (LCx group); and 3)
      left anterior descending (LAD) occlusion (LAD group). Serial cardiac magnetic
      resonance scans were performed to define LA and LV remodeling and ischemic MR,
      and were correlated with histology. RESULTS: Occlusion of the LA branch (LAI
      group) induced a greater degree of LA dilation at 1 and 8 weeks post-MI than the
      LCx and LAD groups, along with early and severe impairment of LA function. In the
      LCx and LAD groups, LA dysfunction was less pronounced and not consistent.
      Development of ischemic MR was more pronounced in the LAI group than in the LCx
      group. Histology confirmed atrial infarction with extensive fibrosis in the LAI
      group and interstitial fibrosis in the LCx group. In the LAD group, LA remodeling
      was not observed by cardiac magnetic resonance or histology. CONCLUSIONS: We
      provide the first experimental evidence of the deleterious effect of acute LAI on
      atrial structural remodeling, characterized by early LA dilation, dysfunction,
      and fibrosis, and early occurrence of ischemic MR.

PMID- 29216986
TI  - Upstream Targets to Treat Atrial Fibrillation.

PMID- 29216985
TI  - Eplerenone Reduces Atrial Fibrillation Burden Without Preventing Atrial
      Electrical Remodeling.
AB  - BACKGROUND: The aldosterone inhibitor eplerenone (EPL) has been shown to reduce
      the incidence of atrial fibrillation (AF) in patients with systolic heart
      failure, but the mechanism is unknown. OBJECTIVES: This study hypothesized that
      by reducing atrial dilation and fibrosis in the absence of heart failure, EPL
      also reduces AF burden and prevents AF perpetuation. METHODS: The authors
      conducted a randomized controlled study in 34 sheep that were atrially tachypaced
      (13 +/- 1 week). They compared daily oral EPL (n = 19) versus sugar pill (SP)
      treatment (n = 15) from the start of tachypacing. The endpoint was a continuous 7
      day stretch of persistent AF (n = 29) or completion of 23 weeks tachypacing (n =
      5). RESULTS: EPL significantly reduced the rate of left atrial dilation increase
      during AF progression. Atria from EPL-treated sheep had less smooth muscle actin
      protein, collagen-III expression, interstitial atrial fibrosis, and cell
      hypertrophy than SP-treated sheep atria did. However, EPL did not modify the AF
      induced increase in the rate of dominant frequency and ion channel densities seen
      under SP treatment, but rather prolonged the time to persistent AF in 26% of
      animals. It also reduced the degree of fibrillatory conduction, AF inducibility,
      and AF burden. CONCLUSIONS: In the sheep model, EPL mitigates fibrosis and atrial
      dilation, modifies AF inducibility and AF complexity, and prolongs the transition
      to persistent AF in 26% of animals, but it does not prevent AF-induced electrical
      remodeling or AF persistence. The results highlight structural remodeling as a
      central upstream target to reduce AF burden, and the need to prevent electrical
      remodeling to avert AF perpetuation.

PMID- 29216987
TI  - Catheter Ablation of Ventricular Tachycardia in Structurally Normal Hearts:
      Indications, Strategies, and Outcomes-Part I.
AB  - Catheter ablation of ventricular tachycardia (VT) is being increasingly
      performed; yet, there is often confusion regarding indications, outcomes, and how
      to identify those patient populations most likely to benefit. The management
      strategy differs between those with structural heart disease and those without.
      For the former, an implantable cardioverter-defibrillator (ICD) is typically
      required due to an elevated risk for sudden cardiac death, and catheter ablation
      can be used as adjunctive therapy to treat or prevent repetitive ICD therapies.
      In contrast, VT or premature ventricular contractions in the setting of a
      structurally normal heart carries a low risk for sudden cardiac death;
      accordingly, there is typically no indication for an ICD. In these patients,
      catheter ablation is considered for symptom management or to treat
      tachycardiomyopathy and is potentially curative. Here, the authors discuss the
      pathophysiology, mechanism, and management of VT that occurs in the setting of a
      structurally normal heart and the role of catheter ablation.

PMID- 29216988
TI  - Catheter Ablation of Ventricular Tachycardia in Structural Heart Disease:
      Indications, Strategies, and Outcomes-Part II.
AB  - In contrast to ventricular tachycardia (VT) that occurs in the setting of a
      structurally normal heart, VT that occurs in patients with structural heart
      disease carries an elevated risk for sudden cardiac death (SCD), and implantable
      cardioverter-defibrillators (ICDs) are the mainstay of therapy. In these
      individuals, catheter ablation may be used as adjunctive therapy to treat or
      prevent repetitive ICD therapies when antiarrhythmic drugs are ineffective or not
      desired. However, certain patients with frequent premature ventricular
      contractions (PVCs) or VT and tachycardiomyopathy should be considered for
      ablation before ICD implantation because left ventricular function may improve,
      consequently decreasing the risk of SCD and obviating the need for an ICD. The
      goal of this paper is to review the pathophysiology, mechanism, and management of
      VT in the setting of structural heart disease and discuss the evolving role of
      catheter ablation in decreasing ventricular arrhythmia recurrence.

PMID- 29216989
TI  - Earning Trust Through Empathy as a Young Interventionalist: "Is This Your First
      Time Doing This?"

PMID- 29216990
TI  - Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular
      Rejection After Heart Transplantation.

PMID- 29216991
TI  - Cardiac betaarrestin2 Improves Contractility and Adverse Remodeling in Heart
      Failure, But Is Underexpressed in Humans.

PMID- 29216992
TI  - Atrial Fibrillation: The Next Epidemic for Patients With Congenital Heart
      Disease.

PMID- 29216993
TI  - Reply: Atrial Fibrillation: The Next Epidemic for Patients With Congenital Heart
      Disease.

PMID- 29216994
TI  - Will Physicians Benefit From Appropriate Use Criteria-Based Education and
      Feedback Intervention?

PMID- 29216995
TI  - Reply: Will Physicians Benefit From Appropriate Use Criteria-Based Education and
      Feedback Intervention?

PMID- 29216996
TI  - Editorial: Tutorials in Bioinformatics for Biological Science.

PMID- 29216998
TI  - Bioresorbable Scaffolds: A Complex Journey to the "Promised Land".

PMID- 29216997
TI  - The State of the Absorb Bioresorbable Scaffold: Consensus From an Expert Panel.
AB  - Significant progress has been made in the percutaneous coronary intervention
      technique from the days of balloon angioplasty to modern-day metallic drug
      eluting stents (DES). Although metallic stents solve a temporary problem of acute
      recoil following balloon angioplasty, they leave behind a permanent problem
      implicated in very late events (in addition to neoatherosclerosis). BRS were
      developed as a potential solution to this permanent problem, but the promise of
      these devices has been tempered by clinical trials showing increased risk of
      safety outcomes, both early and late. This is not too dissimilar to the
      challenges seen with first-generation DES in which refinement of deployment
      technique, prolongation of dual antiplatelet therapy, and technical iteration
      mitigated excess risk of very late stent thrombosis, making DES the treatment of
      choice for coronary artery disease. This white paper discusses the factors
      potentially implicated in the excess risks, including the scaffold consideration
      and deployment technique, and outlines patient and lesion selection, implantation
      technique, and dual antiplatelet therapy considerations to potentially mitigate
      this excess risk with the first-generation thick strut Absorb scaffold (Abbott
      Vascular, Abbott Park, Illinois). It remains to be seen whether these
      considerations together with technical iterations will ultimately close the gap
      between scaffolds and metal stents for short-term events while at the same time
      preserving options for future revascularization once the scaffold bioresorbs.

PMID- 29216999
TI  - Characteristics, Predictors, and Mechanisms of Thrombosis in Coronary
      Bioresorbable Scaffolds: Differences Between Early and Late Events.
AB  - OBJECTIVES: The study sought to investigate the incidence, characteristics,
      predictors, and possible mechanisms of early and 3-year coronary scaffold
      thrombosis (ScT). BACKGROUND: An increased incidence of both early and late ScT
      has been shown in randomized trials. METHODS: Consecutive patients were enrolled
      in a single-center registry. Quantitative coronary angiography was performed.
      Incidence and predictors of ScT were assessed with Kaplan-Meier and Cox
      regression analyses. RESULTS: A total of 657 patients (63 +/- 12 years of age,
      79% men, 21% diabetic, 64% acute coronary syndrome) who received 925 coronary
      bioresorbable scaffolds (BRS) (Abbott Vascular, Santa Clara, California) between
      May 2012 and January 2015 were enrolled. Clinical and procedural characteristics
      and outcome data at 1,076 (interquartile range: 762 to 1,206) days (3-year follow
      up rate 93%) were collected. Twenty-eight ScTs were recorded: 14 early (Kaplan
      Meier estimate: 2.2%), 5 late (Kaplan-Meier estimate: 0.9%), and 9 very late
      (Kaplan-Meier estimate: 1.7%). The incidence of ScT followed a U-shaped curve
      with highest incidence at the extremes of the distributions of reference vessel
      diameter (RVD) and the ratio of BRS nominal diameter to RVD. At quantitative
      coronary angiography, RVD (hazard ratio [HR]: 0.14; 95% confidence interval [CI]:
      0.04 to 0.49) and BRS oversizing (ratio of BRS nominal diameter to RVD >1.15; HR:
      107.40; 95% CI: 9.20 to 1,261.30) emerged as potent predictors of early ScT. RVD
      (HR: 9.55; 95% CI: 3.90 to 23.42) and BRS undersizing (ratio of BRS nominal
      diameter to RVD <0.85; HR: 0.0004; 95% CI: 0.0000 to 0.0400) predicted late or
      very late ScT (all p < 0.0001). The incidence of both early and late or very late
      ScT were lower (~80% reduction) when an optimal implantation technique was used.
      The most important factor appeared to be vessel and BRS sizing. CONCLUSIONS:
      Different mechanisms underlie early and late ScT: although incomplete BRS
      deployment was a predictor of the former, the latter was associated with large
      vessel size and BRS undersizing. However, both phenomena are significantly less
      frequent with an optimized implantation technique. (Mainz Intracoronary Database.
      The Coronary Slow-flow and Microvascular Diseases Registry [MICAT]; NCT02180178).

PMID- 29217000
TI  - Early and Late Bioresorbable Vascular Scaffold Thrombosis: Size Matters.

PMID- 29217003
TI  - Left Main Disease: At the Intersection of Surgery and Stents.

PMID- 29217001
TI  - Long-Term Safety and Efficacy of Platinum Chromium Everolimus-Eluting Stents in
      Coronary Artery Disease: 5-Year Results From the PLATINUM Trial.
AB  - OBJECTIVES: The authors sought to evaluate the final 5-year safety and
      effectiveness of the platinum-chromium everolimus-eluting stent (PtCr-EES) in the
      randomized trial, as well as in 2 single-arm substudies that evaluated PtCr-EES
      in small vessels (diameter <2.5 mm; n = 94) and long lesions (24 to 34 mm; n =
      102). BACKGROUND: In the multicenter, randomized PLATINUM (PLATINUM Clinical
      Trial to Assess the PROMUS Element Stent System for Treatment of De Novo Coronary
      Artery Lesions), the PtCr-EES was noninferior to the cobalt-chromium everolimus
      eluting stent (CoCr-EES) at 1 year in 1,530 patients undergoing percutaneous
      coronary intervention. METHODS: Patients with 1 or 2 de novo coronary artery
      lesions (reference vessel diameter 2.50 to 4.25 mm, length <=24 mm) were
      randomized 1:1 to PtCr-EES versus CoCr-EES. All patients in the substudies
      received PtCr-EES. The primary endpoint was target lesion failure (TLF), a
      composite of target vessel-related cardiac death, target vessel-related
      myocardial infarction, or ischemia-driven target lesion revascularization.
      RESULTS: In the randomized trial, the 5-year TLF rate was 9.1% for PtCr-EES and
      9.3% for CoCr-EES (hazard ratio [HR]: 0.97; p = 0.87). Landmark analysis
      demonstrated similar TLF rates from discharge to 1 year (HR: 1.12; p = 0.70) and
      from 1 to 5 years (HR: 0.90; p = 0.63). There were no significant differences in
      the rates of cardiac death, myocardial infarction, target lesion or vessel
      revascularization, or stent thrombosis. PtCr-EES had 5-year TLF rates of 7.0% in
      small vessels and 13.6% in long lesions. CONCLUSIONS: PtCr-EES demonstrated
      comparable safety and effectiveness to CoCr-EES through 5 years of follow-up,
      with low rates of stent thrombosis and other adverse events. The 5-year event
      rates were also acceptable in patients with small vessels and long lesions
      treated with PtCr-EES. (The PLATINUM Clinical Trial to Assess the PROMUS Element
      Stent System for Treatment of De Novo Coronary Artery Lesions [PLATINUM];
      NCT00823212; The PLATINUM Clinical Trial to Assess the PROMUS Element Stent
      System for Treatment of De Novo Coronary Artery Lesions in Small Vessels
      [PLATINUM SV]; NCT01498692; The PLATINUM Clinical Trial to Assess the PROMUS
      Element Stent System for Treatment of Long De Novo Coronary Artery Lesions
      [PLATINUM LL]; NCT01500434).

PMID- 29217002
TI  - The DELTA 2 Registry: A Multicenter Registry Evaluating Percutaneous Coronary
      Intervention With New-Generation Drug-Eluting Stents in Patients With Obstructive
      Left Main Coronary Artery Disease.
AB  - OBJECTIVES: The aim of this study was to evaluate clinical outcomes of
      unprotected left main coronary artery percutaneous coronary intervention (PCI)
      with new-generation drug-eluting stents in a "real world" population. BACKGROUND:
      PCI of the unprotected left main coronary artery is currently recommended as an
      alternative to coronary artery bypass grafting (CABG) in selected patients.
      METHODS: All consecutive patients with unprotected left main coronary artery
      stenosis treated by PCI with second-generation drug-eluting stents were analyzed
      in this international, all-comers, multicenter registry. The results were
      compared with those from the historical DELTA 1 (Drug Eluting Stent for Left Main
      Coronary Artery) CABG cohort using propensity score stratification. The primary
      endpoint was the composite of death, myocardial infarction (MI), or stroke at the
      median time of follow-up. RESULTS: A total of 3,986 patients were included. The
      mean age was 69.6 +/- 10.9 years, diabetes was present in 30.8%, and 21% of the
      patients presented with acute MI. The distal left main coronary artery was
      involved in 84.6% of the lesions. At a median of 501 days (~17 months) of follow
      up, the occurrence of the primary endpoint of death, MI, or cerebrovascular
      accident was lower in the PCI DELTA 2 group compared with the historical DELTA 1
      CABG cohort (10.3% vs. 11.6%; adjusted hazard ratio: 0.73; 95% confidence
      interval: 0.55 to 0.98; p = 0.03). Of note, an advantage of PCI was observed with
      respect to cerebrovascular accident (0.8% vs. 2.0%; adjusted hazard ratio: 0.37;
      95% confidence interval: 0.16 to 0.86; p = 0.02), while an advantage of CABG was
      observed with respect to target vessel revascularization (14.2% vs. 2.9%;
      adjusted hazard ratio: 3.32; 95% confidence interval: 2.12 to 5.18; p < 0.0001).
      CONCLUSIONS: After a median follow-up period of 17 months, PCI with new
      generation drug-eluting stents was associated with an overall low rate of the
      composite endpoint of death, MI, or cerebrovascular accident.

PMID- 29217005
TI  - Transapical Approach: Learn From the Past, Move Toward the Future.

PMID- 29217004
TI  - Transapical Transcatheter Aortic Valve Replacement Is Associated With Increased
      Cardiac Mortality in Patients With Left Ventricular Dysfunction: Insights From
      the PARTNER I Trial.
AB  - OBJECTIVES: The authors sought to evaluate the impact of transapical (TA)
      transcatheter aortic valve replacement (TAVR) on mortality, left ventricular (LV)
      ejection fraction (LVEF) improvement, and functional recovery in patients with LV
      dysfunction. BACKGROUND: LV injury inherent to TA access for structural heart
      disease interventions may be particularly detrimental to the LV, functional
      recovery, and survival in patients with LV dysfunction. METHODS: The study
      included patients enrolled within the PARTNER I (Placement of Aortic
      Transcatheter Valves) trial that underwent transfemoral (TF) or TA TAVR. Analyses
      of clinical outcomes were stratified by the presence of baseline LV dysfunction
      (LVEF<50%) and adjusted for the propensity of receiving TA TAVR. RESULTS: Of
      2,084 subjects, 1,057 underwent TA TAVR. TA access was associated with increased
      2-year all-cause mortality in those with (adjusted hazard ratio [HRadjusted]:
      1.52; 95% confidence interval [CI]: 1.12 to 2.07; p = 0.008) and without
      (HRadjusted: 1.38; 95% CI: 1.10 to 1.74; p = 0.006) LV dysfunction. TA TAVR
      portended increased 2-year cardiac mortality in subjects with LVEF<50%
      (HRadjusted: 1.92; 95% CI: 1.21 to 3.05; p = 0.006), but not with LVEF>=50%
      (HRadjusted: 1.29; 95% CI: 0.87 to 1.90; p = 0.21). In those with LVEF<50%,
      greater improvements in LVEF (TF-TA difference +4.04%, 95% CI: 2.39% to 5.69%; p
      < 0.0001) and 6-min walk distance (TF-TA difference +45.1 m, 95% CI: 18.4 to 71.9
      m; p = 0.001) occurred within 30 days after TF versus TA TAVR. CONCLUSIONS:
      Compared with TF TAVR, TA TAVR is associated with a disproportionate risk of
      cardiac mortality in patients with LV dysfunction and with delayed and less
      robust improvement in LV function and overall functional status. Caution is
      warranted when considering TA access for structural heart disease interventions,
      particularly in patients with LV dysfunction. (Placement of Aortic Transcatheter
      Valves [PARTNER]; NCT00530894).

PMID- 29217007
TI  - The Transcatheter Aortic Valve Replacement Bounce-Back: Does it Matter? What Can
      Be Done?

PMID- 29217006
TI  - Incidence, Prognostic Impact, and Predictive Factors of Readmission for Heart
      Failure After Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: The aim of this study was to assess the incidence, prognostic impact,
      and predictive factors of readmission for congestive heart failure (CHF) in
      patients with severe aortic stenosis treated by transcatheter aortic valve
      replacement (TAVR). BACKGROUND: TAVR is indicated in patients with severe
      symptomatic aortic stenosis in whom surgery is considered high risk or is
      contraindicated. Readmission for CHF after TAVR remains a challenge, and data on
      prognostic and predictive factors are lacking. METHODS: All patients who
      underwent TAVR from January 2010 to December 2014 were included. Follow-up was
      achieved for at least 1 year and included clinical and echocardiographic data.
      Readmission for CHF was analyzed retrospectively. RESULTS: This study included
      546 patients, 534 (97.8%) of whom were implanted with balloon-expandable valves
      preferentially via the transfemoral approach in 87.8% of cases. After 1 year, 285
      patients (52.2%) had been readmitted at least once, 132 (24.1%) for CHF. Patients
      readmitted for CHF had an increased risk for death (p < 0.0001) and cardiac death
      (p < 0.0001) compared with those not readmitted for CHF. On multivariate
      analysis, aortic mean gradient (hazard ratio [HR]: 0.88; 95% confidence interval
      [CI]: 0.79 to 0.99; p = 0.03), post-procedural blood transfusion (HR: 2.27; 95%
      CI: 1.13 to 5.56; p = 0.009), severe post-procedural pulmonary hypertension (HR:
      1.04; 95% CI: 1.00 to 1.07; p < 0.0001), and left atrial diameter (HR: 1.47; 95%
      CI: 1.08 to 2.01; p = 0.02) were independently associated with CHF readmission at
      1 year. CONCLUSIONS: Readmission for CHF after TAVR was frequent and was strongly
      associated with 1-year mortality. Low gradient, persistent pulmonary
      hypertension, left atrial dilatation, and transfusions were predictive of
      readmission for CHF.

PMID- 29217009
TI  - Endovascular-First Approach for Chronic Mesenteric Ischemia: The Critical Need
      for Reporting Standards and High-Grade Evidence.

PMID- 29217008
TI  - Endovascular Versus Surgical Revascularization for Chronic Mesenteric Ischemia:
      Insights From the National Inpatient Sample Database.
AB  - OBJECTIVES: This study sought to compare in-hospital major adverse cardiac and
      cerebrovascular events (MACCE) following endovascular therapy with open surgery
      for chronic mesenteric ischemia (CMI). BACKGROUND: There are limited contemporary
      data on in-hospital cardiovascular outcomes among patients with CMI undergoing
      revascularization via endovascular therapy versus open surgery in the United
      States. METHODS: Patients with CMI undergoing endovascular or surgical
      (mesenteric bypass or endarterectomy) revascularization between 2007 and 2014
      were identified from the National Inpatient Sample. Weighted national estimates
      were obtained. Primary and secondary endpoints were MACCE (death, myocardial
      infarction, stroke, cardiac post-operative complications) and composite in
      hospital complications (MACCE + post-operative peripheral vascular complications,
      gastrointestinal hemorrhage, major bleeding, and bowel resection), respectively.
      Propensity score matching was used to obtain a balanced cohort of 880 unweighted
      patients in each group. RESULTS: Of 4,150 patients with CMI, 3,206 (77.2%)
      underwent endovascular therapy and 944 (22.8%) underwent surgery (weighted
      national estimates of 15,850 and 4,687, respectively). In the propensity-matched
      cohort, MACCE and composite in-hospital complications occurred significantly less
      often after endovascular therapy than surgery (8.6% vs. 15.9%; p < 0.001; and
      15.3% vs. 20.3%; p < 0.006). Endovascular therapy was also associated with lower
      median hospital costs ($20,807.00 [interquartile range: $13,640.20 to $32.754.50]
      vs. $31,137.00 [interquartile range: $21,680.40 to $52,152.20]; p < 0.001,
      respectively) and shorter length of stay (5 [interquartile range: 2 to 10] vs. 10
      [interquartile range: 7 to 17] days, respectively; p < 0.001) compared with open
      surgery. CONCLUSIONS: In a large, retrospective analysis of patients with CMI,
      endovascular therapy remained the dominant revascularization modality, and was
      associated with lower rates of MACCE, composite in-hospital complications, lower
      costs, and shorter length of stay compared with surgery.

PMID- 29217010
TI  - Parasympathetic Stimulation in Acute Myocardial Infarction: Is There a Role for a
      Pharmacologic Alternative Beyond Vagal Electrical Stimulation?

PMID- 29217011
TI  - Reply: Parasympathetic Stimulation in Acute Myocardial Infarction: Is There a
      Role for a Pharmacologic Alternative Beyond Vagal Electrical Stimulation?

PMID- 29217012
TI  - Cangrelor or Abciximab as First Choice in Cardiogenic Shock.

PMID- 29217013
TI  - Reply: Cangrelor or Abciximab as First Choice in Cardiogenic Shock.

PMID- 29217014
TI  - Early Risk Stratification in Patients With Cardiogenic Shock Complicating Acute
      Myocardial Infarction Treated With Extracorporeal Life Support and Primary
      Percutaneous Coronary Intervention.

PMID- 29217015
TI  - Intrastent Hematoma After Pre-Dilatation for 17-Month Restenosis of
      Polytetrafluoroethylene-Covered Stent: Insights From Intravascular Imaging.

PMID- 29217017
TI  - Innovation in Ophthalmology.

PMID- 29217016
TI  - Treatment of End-Stage Heart Failure by Transcatheter Closure of Arteria Iliaca
      Communis-Venae Cava Inferior Fistula Caused by Traumatism.

PMID- 29217018
TI  - L'innovation en ophtalmologie.

PMID- 29217019
TI  - Effect of music on surgical skill during simulated intraocular surgery.
AB  - OBJECTIVE: To evaluate the effect of Mozart music compared to silence on anterior
      segment surgical skill in the context of simulated intraocular surgery. DESIGN:
      Prospective stratified and randomized noninferiority trial. PARTICIPANTS:
      Fourteen ophthalmologists and 12 residents in ophthalmology. METHODS: All
      participants were asked to perform 4 sets of predetermined tasks on the EyeSI
      surgical simulator (VRmagic, Mannheim, Germany). The participants completed 1
      Capsulorhexis task and 1 Anti-Tremor task during 3 separate visits. The first 2
      sets determined the basic level on day 1. Then, the participants were stratified
      by surgical experience and randomized to be exposed to music (Mozart sonata for 2
      pianos in D-K448) during either the third or the fourth set of tasks (day 2 or
      3). Surgical skill was evaluated using the parameters recorded by the simulator
      such as "Total score" and "Time" for both tasks and task-specific parameters such
      as "Out of tolerance percentage" for the Anti-Tremor task and "Deviation of
      rhexis radius from 2.5 mm," "Roundness," and "Centering" for the Capsulorhexis
      task. The data were analyzed using the Wilcoxon signed-rank test. RESULTS: No
      statistically significant differences were noted between exposure and nonexposure
      for all the Anti-Tremor task parameters as well as most parameters for the
      Capsulorhexis task. Two parameters for the Capsulorhexis task showed a strong
      trend for improvement with exposure to music ("Total score" +23.3%, p = 0.025;
      "Roundness" +33.0%, p = 0.037). CONCLUSION: Exposure to music did not negatively
      impact surgical skills. Moreover, a trend for improvement was shown while
      listening to Mozart music.

PMID- 29217020
TI  - Cataract surgery outcomes and complications in retinal dystrophy patients.
AB  - OBJECTIVE: To investigate intraoperative complications, postoperative findings,
      and visual acuity outcomes in patients with retinal dystrophy after cataract
      surgery. DESIGN: Retrospective chart review at an academic tertiary referral
      centre. PARTICIPANTS: Thirty eyes from 18 patients with retinitis pigmentosa and
      other retinal dystrophies (Usher syndrome, Refsum disease, and Leber congenital
      amaurosis) who underwent cataract surgery were identified by searching the
      electronic medical record system from January 2010 to September 2015 for all
      patients treated by a single physician with billing codes for retinal dystrophy
      and cataract surgery. METHODS: Cases were reviewed to determine indication for
      surgery, intraoperative complications, postoperative findings, preoperative
      visual acuity, 1-month postoperative visual acuity, and patient subjective
      satisfaction. RESULTS: Mean best-corrected visual acuity significantly improved
      after cataract surgery, from 1.09 +/- 0.69 preoperatively to 0.614 +/- 0.448 at 1
      month postoperatively, on logMAR scale (p = 0, Wilcoxon test). The most common
      postoperative finding was posterior capsule opacification in 20 eyes (66.7%).
      Visually significant cystoid macular edema occurred in 4 eyes (13.3%) despite the
      postoperative eye drop regimen. Patient satisfaction at 1 month postoperatively
      was noted as 93.3% (28 eyes) and attributed mostly to improved central vision and
      reduced glare symptoms. CONCLUSIONS: Patients with visually significant cataract
      in association with retinal dystrophy have significantly improved best-corrected
      visual acuity after cataract surgery and report subjectively improved visual
      functioning. This study confirms that several risks factors are greater in
      patients with retinal dystrophy, including zonular weakness, posterior capsular
      opacification, and cystoid macular edema, compared with the general cataract
      population.

PMID- 29217021
TI  - Practice patterns in the interdisciplinary management of corneal abrasions.
AB  - OBJECTIVE: To characterize the treatment and follow-up patterns of corneal
      abrasions at an academic health centre. METHODS: This is a retrospective review
      of 90 cases of corneal abrasions over a 2-year period at a tertiary care academic
      hospital, of which 75 were seen by the ophthalmology department. All
      consultations primarily for corneal abrasion, as determined by the emergency
      department physician, were included in the study. Information on treatment
      regimen, corneal findings by emergency and ophthalmology physicians, time between
      follow-ups, and final outcomes was collected. RESULTS: Seventy-five patients were
      seen by ophthalmology a median of 1 day after the emergency room visit. Twenty
      five of these patients did not arrive for their subsequent follow-up appointment.
      Twenty-two of the abrasions were healed by the time of the ophthalmology
      examination, 51 patients had unhealed corneal abrasions, and 2 had corneal
      ulcers. Management was changed in 29 of the patients by ophthalmology. The most
      common management changes were hypertonic saline ointment for prophylaxis or
      treatment of recurrent erosion syndrome, followed by bandage contact lenses for
      comfort. CONCLUSIONS: Corneal abrasions are a common condition, and practice
      patterns for follow-up vary widely. Although the vast majority of patients do
      very well and likely would heal on their own without ophthalmology referral, it
      seems reasonable that patients with corneal abrasions are assessed once by an
      ophthalmologist immediately or possibly up to 1-2 days after the initial
      emergency visit, depending on the individual patient circumstances.

PMID- 29217022
TI  - Focal limbal stem cell deficiency associated with soft contact lens wear.
AB  - OBJECTIVE: The aim of this study is to summarize the clinical characteristics of
      patients with contact lens-associated focal limbal stem cell deficiency (FLSCD)
      from a tertiary corneal referral centre. DESIGN: Retrospective, observational
      case series in a tertiary care centre. METHODS: Patients with contact lens
      associated FLCSD were identified in our database. Clinical data were retrieved by
      chart review. A questionnaire asking for contact lens brand, type, cleaning
      solution, and duration of contact lens wear was sent to the patients with
      telephone follow-up. Clinical features and recovery time were identified.
      RESULTS: Twenty-seven eyes of 17 patients were identified with superior corneal
      whorl-like patches of opaque epithelium, sometimes accompanied by
      neovascularization. Of the patients, 17/17 used soft contact lenses, with a mean
      wearing duration of 11.4 hours per day. Patients had been wearing lenses for an
      average of 18.1 years. Silicone hydrogel lenses were noted in 12/17 cases. LSCD
      was superior in all 27 eyes, and all of them improved with contact lens wear
      cessation, preservative-free topical steroids, and preservative-free artificial
      tears. Visual acuity improved from 20/28 to 20/22 (p < 0.001). CONCLUSIONS:
      Contact lens-associated FLSCD typically presents in the superior cornea with
      whorl-like epithelial opacities advancing from the limbus. Conservative medical
      treatment is available and shows a high success rate after a slow recovery.

PMID- 29217023
TI  - Visual impairment as an independent risk factor for falls in hospitalized
      patients.
AB  - OBJECTIVE: To investigate the association between visual impairment and the risk
      of falls in hospitalized patients. DESIGN: Individually matched case-control
      study. METHODS: The medical records of patients who fell while hospitalized at
      Juntendo Tokyo Koto Geriatric Medical Center (JTKGMC) from January to December
      2014 were reviewed retrospectively. Among them, 36 patients who were recorded as
      visiting the Ophthalmology Outpatient Clinic from 1 year before to 1 year after
      the fall were included as cases. As the control subjects, 36 individually matched
      patients were chosen who were hospitalized in the same beds in the same hospital
      wards. Visual impairment and blindness were defined according to U.S. criteria.
      Conditional logistic regression analysis was used for both univariate and
      multivariate analyses. Based on previous reports, multivariate analysis was
      performed with adjustment for age, sex, a history of falls, and use of walking
      aids. This study was approved by the institutional review board of JTKGMC and was
      performed according to the tenets of the Declaration of Helsinki. RESULTS: The
      crude odds ratio (OR) for visual impairment was 6.0 (95% confidence interval
      [CI]: 0.72-49.83). For a history of falls and use of walking aids, the crude OR
      (95% CI) was 2.5 (0.97-6.44) and 2.8 (0.88-8.64), respectively. After adjustment
      for age, sex, a history of falls, and use of walking aids, the association
      between falls and visual impairment was significant (OR: 13.9; 95% CI: 1.0004
      194.41). CONCLUSION: These findings suggest that visual impairment could be an
      independent risk factor for falls among hospitalized patients.

PMID- 29217024
TI  - Improving patient identification in an ophthalmology clinic using name alerts.
AB  - OBJECTIVE: To develop a standardized process for reviewing daily patient lists
      and identifying potential risks of misidentification. Our goal was to develop a
      proactive approach to identify and eliminate risks of patient misidentification.
      METHODS: Assessment of current patient identification practices took place over a
      period of 4 weeks. Using a process map, a patient survey was developed to
      determine the encounter points when patient identification was confirmed. This
      information was used to develop a standardized protocol for review of daily
      appointment lists. RESULTS: Review of daily appointment lists was completed to
      identify potential similar/same name risks. A standardized manual process of
      chart review, flagging, and tracking was developed. CONCLUSIONS: The name alert
      process resulted in a simple manual process for identifying which patients have a
      higher name risk and allowed care providers to take preventative action to
      decrease potential risk of incorrect diagnostic testing, procedure, or medication
      administration.

PMID- 29217025
TI  - Correlation of novel PAX6 gene abnormalities in aniridia and clinical
      presentation.
AB  - OBJECTIVE: To describe the clinical presentation and genotype of subjects with
      aniridia with a particular focus on foveal hypoplasia. DESIGN: Prospective cohort
      study. PARTICIPANTS: Thirty-three Canadian participants with aniridia and of
      various ethnic backgrounds residing in British Columbia. METHODS: Full ophthalmic
      examinations and posterior segment spectral domain-optical coherence tomography
      (SD-OCT) imaging were performed. Foveal hypoplasia was graded independently by 2
      staff ophthalmologists. PAX6 sequencing was performed and chromosomal 11p
      anomalies investigated. Candidate gene and single-nucleotide polymorphism
      sequencing in genes functionally related to PAX6 were also studied. RESULTS: Best
      corrected visual acuities in the cohort ranged from 0.0 logMAR to no light
      perception. Total absence of iris tissue was seen in the majority (42 of 66
      eyes). In those in whom SD-OCT was possible, foveal hypoplasia was seen in the
      majority (45 of 56 eyes, 80%). Molecular genetic defects involving PAX6 were
      identified in 30 participants (91%), including 4 novel PAX6 mutations (Gly18Val;
      Ser65ProfsX14; Met337ArgfsX18; Ser321CysfsX34) and 4 novel chromosome 11p
      deletions inclusive of PAX6 or a known PAX6 regulatory region. CONCLUSIONS: The
      number of PAX6 mutations associated with aniridia continues to increase. Variable
      foveal architecture despite nearly identical anterior segment disease in 4
      participants with an Ex9 ELP4-Ex4 DCDC1 deletion suggested that molecular cues
      causing variation in disease in the posterior segment differ from those at play
      in the anterior segment. Results in 3 patients without identifiable PAX6
      mutations and a review of the literature suggest that such cases be described as
      phenocopies rather than actual cases of the syndrome of aniridia.

PMID- 29217026
TI  - Ciliary body location in eyes with and without primary congenital glaucoma.
AB  - OBJECTIVE: To compare the location of ciliary body (CB) in children with and
      without primary congenital glaucoma (PCG). METHODS: In this cross-sectional
      study, we enrolled Saudi children who were less than 5 years old. CB distance
      (CBD) was measured and compared in eyes with PCG (PCG group) and without PCG
      (control group). CBD was measured with a caliper and defined as the distance
      between the edge of the corneoscleral limbus and the anterior edge of CB as
      delineated by transillumination. The difference in the CBD between groups was
      correlated with the axial length, corneal thickness, and corneal diameter.
      RESULTS: CBD was measured in 15 eyes in the PCG and control groups. The mean CBD
      (1.6 +/- 0.4 mm) in the PCG group was significantly greater than that in the
      control group (1.3 +/- 0.3 mm) (p < 0.001). The mean difference in the CBD of 2
      groups was 0.33 mm (95% CI 0.15-0.54). In PCG eyes, the CBD was farthest in the
      superior quadrant (1.7 mm) followed by inferior (1.6 mm), temporal (1.6 mm), and
      nasal (1.5 mm) quadrants. The variability in CBD between quadrants in PCG eyes
      was greater than that in the control group. CBD in the PCG group showed a
      significant correlation with increasing axial length (p = 0.05), corneal
      thickness (p < 0.001), and corneal diameter (p = 0.0002). CONCLUSIONS: The CBD
      from the limbus was greater in PCG eyes compared to the controls and varied
      significantly in different quadrants. The knowledge regarding the greater CBD and
      its variability in PCG eyes could enable better planning of surgical treatment in
      congenital glaucoma.

PMID- 29217027
TI  - Optic disc hemorrhages in glaucoma and common clinical features.
AB  - OBJECTIVE: To analyze optic nerve head stereophotographs for the presence of
      optic disc hemorrhages, and to describe bleeding patterns and patient
      characteristics. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: 1113
      optic nerve stereophotograph pairs of 562 consecutive patients. METHODS:
      Stereophotographs were systematically reviewed for the presence of a disc
      hemorrhage with careful documentation of optic nerve head features. All charts of
      patients with hemorrhage were subsequently studied for demographic information
      and clinical data. RESULTS: Disc hemorrhages were observed in 7.1% of patients
      with optic disc photography. Most patients had open-angle glaucoma (57.5%) with
      focal ischemic phenotype of the optic disc (66.7%). The mean vertical and
      horizontal cup-disc ratios were 0.82 +/- 0.14 and 0.76 +/- 0.14, respectively.
      The beta-zone peripapillary atrophy was observed in 48.9% of patients. The most
      common location was the inferotemporal region of the disc (60.8%), and most were
      flame or splinter shaped (70.6%). Disc hemorrhages were found either superficial
      to or within the retinal nerve fibre layer (72.5%), and in association with a
      notch (64.4%). The average intraocular pressure was 17.3 +/- 4.9 mm Hg, and most
      hemorrhages were associated with early visual field defects (42.5%). CONCLUSIONS:
      Optic disc hemorrhages in patients with glaucoma were most frequently observed
      inferiorly in association with a notch. Most eyes with a disc hemorrhage had an
      intraocular pressure within normal range and had either early or no visual field
      loss. These findings highlight the importance of careful examination of the optic
      nerve head to look for the presence of a disc hemorrhage as an important
      biomarker of glaucoma damage.

PMID- 29217028
TI  - Epidemiological trends in 1452 cases of retinoblastoma from the Surveillance,
      Epidemiology, and End Results (SEER) registry.
AB  - OBJECTIVE: To assess retinoblastoma epidemiological trends in the Surveillance,
      Epidemiology, and End Results (SEER) registry. METHODS: All cases of
      retinoblastoma in the SEER database from 1973 to 2009 were identified. Kaplan
      Meier survival analyses were performed for pathological grade, patient age, sex,
      year of diagnosis, and treatment modality. Cox proportional hazards regression
      assessed the impact of patient and tumour characteristics on survival. RESULTS:
      1452 cases of retinoblastoma were analyzed. The mean patient age at diagnosis was
      1.44 years. The tumour was unilateral in 71.0% and bilateral in 29.0%. The mean
      follow-up was 129.1 months. Overall survival increased during the study interval.
      Patients with bilateral tumours were diagnosed at an earlier age (0.46 years)
      than patients with unilateral disease (1.77 years; p < 0.0001). Bilateral
      retinoblastoma (90.3% 10-year overall survival) was associated with decreased
      overall survival than unilateral retinoblastoma (96.1% 10-year overall survival).
      Bilateral retinoblastoma was also associated with an increased incidence of
      nonocular malignancies (7.8%) compared with unilateral retinoblastoma (1.3%; p <
      0.0001). Grade 1 tumours were diagnosed at a younger age (0.94 years) than grade
      3 (2.24 years) and grade 4 tumours (2.14 years; p < 0.0001). Lower grade and
      lower stage tumours were independently associated with increased survival. In
      multivariate Cox proportional hazards analysis, T stage and laterality were the
      only covariates that correlated with overall survival. CONCLUSIONS: There appear
      to be associations between retinoblastoma tumour features such as tumour stage,
      pathological grade, and laterality with patient characteristics such as age at
      diagnosis, overall survival, and second malignancies.

PMID- 29217029
TI  - Development of a predictive model for temporal artery biopsies.
AB  - OBJECTIVE: Temporal artery biopsy is a critical, relatively safe, and reliable
      test in the diagnosis of temporal arteritis. Yet, a clarification of the pre-test
      probabilities may provide clarity on which patients with suspected giant cell
      arteritis would benefit from this invasive diagnostic procedure. DESIGN: A
      prospective case series PARTICIPANTS: A consecutive case series of patients
      referred to the Ophthalmology service for temporal artery biopsy. METHODS: All
      subjects underwent standardized serum testing, and signs and symptoms assessment.
      Predictive models were created and evaluated. RESULTS: 119 patients were
      analyzed. This exploratory study found that a simple model including platelet
      count, erythrocyte sedimentation rate, and c-reactive protein was able to define
      a subset of patients with a pre-test probability of a positive biopsy of 0% or
      100%. 40% (95% confidence interval 31%-49%) of patients fell into this category.
      CONCLUSIONS: Utilizing a simple clinically applicable predictive model of the
      pretest probability of a temporal artery biopsy in patients with suspected giant
      cell arteritis, up to 31%-49% of temporal artery biopsies may be avoided. This
      study was a single site exploratory study with data-driven thresholds - therefore
      these results need to be validated with an independent sample prior to clinical
      use.

PMID- 29217030
TI  - Perforated punctal plugs with adjuvant use of mitomycin-C in management of
      acquired external punctal stenosis grades 0 and 1.
AB  - OBJECTIVE: To evaluate the use of perforated punctal plugs with adjuvant
      application of mitomycin-C in the management of acquired external punctal
      stenosis grades 0 and 1. METHODS: This is a prospective interventional case
      series including 30 eyes of 30 patients with acquired external punctal stenosis
      of the lower punctum of grades 0 and 1 presenting with epiphora. They were
      examined to exclude other causes of lacrimation and epiphora: Slit-lamp
      assessment of the stenosed punctum and grading was done, probing was done to
      exclude associated canalicular stenosis, and syringing was done to exclude
      nasolacrimal duct obstruction. For all cases, dilatation was done, followed by
      application of mitomycin-C, and perforated punctal plugs were then inserted.
      Plugs were removed after 6 months, and anatomical and functional success were
      assessed and followed during and for 6 months after removal of the plugs.
      RESULTS: The study included 30 patients with acquired external punctal stenosis:
      9 males (30%) and 21 females (70%) with a mean age of 62.83 +/- 8.3 years.
      Punctal stenosis grade 0 (no punctum) occurred in 9 cases (30%), and grade 1 (the
      punctum is covered by a membrane) occurred in 21 cases (70%). Six months after
      removal of the plugs, epiphora improved in 93.3% of patients, and fluorescein dye
      disappearance test results improved in 90% of patients; 6.7% of cases had early
      extrusion of the plug, and 3.3% had granuloma formation. CONCLUSIONS: Application
      of perforated punctal plugs combined with mitomycin-C is a simple and efficient
      technique in the management of tight acquired external punctal stenosis.

PMID- 29217031
TI  - Early postoperative overcorrection in recurrent exotropia.
AB  - OBJECTIVE: To investigate the surgical outcome according to the angle of
      deviation at postoperative day 1 in patients with recurrent exotropia DESIGN:
      Retrospective case series METHODS: Surgical outcome in patients with recurrent
      exotropia for at least 1 year was analyzed retrospectively. Patients were divided
      into 3 subgroups according to the angle of deviation at postoperative day 1:
      overcorrection group (>=2 prism diopter [PD] of esodeviation), orthotropic group
      (orthotropia or <5 PD of exodeviation), and undercorrection group (>=5 PD of
      exodeviation). Success was defined as <=5 PD of esodeviation or <=10 PD of
      exodeviation at the final visit. RESULTS: One hundred and six patients were
      included in this study. Age at surgery was 11.8 +/- 6.9 years, and preoperative
      angle of deviation was 22.9 +/- 6.3 PD at distant. Patients were followed-up for
      24.4 +/- 12.8 months. There were 20 (18.9%), 82 (77.4%), and 4 (3.8%) patients in
      overcorrection, orthotropic, and undercorrection groups at postoperative day 1 (p
      = 0.001). The surgical success rate at the final visit in the overcorrection
      group (95%) was higher than that in orthotropic and undercorrection groups (76.8%
      and 25%, respectively, p = 0.004). In univariate regression analysis,
      overcorrection at postoperative day 1 was the only reliable factor for long-term
      success (odds ratio [OR] = 24.101, p = 0.01). CONCLUSION: Overcorrection at
      postoperative day 1 is a good surgical predictor of successful outcome in surgery
      for recurrent exotropia.

PMID- 29217033
TI  - Ophthalmology at the University of Alberta: Over 8 Decades of People-driven
      Contributions.

PMID- 29217032
TI  - Comparison of endophthalmitis rates following intravitreal injection of
      compounded bevacizumab, ranibizumab, and aflibercept.
AB  - OBJECTIVE: Whereas the incidence of endophthalmitis after compounded intravitreal
      bevacizumab is known to be low, the rates of endophthalmitis after intravitreal
      injection of compounded ranibizumab and aflibercept are not known. The purpose of
      this study was to determine the incidence of endophthalmitis after treatment with
      compounded intravitreal ranibizumab and aflibercept and to compare this to the
      incidence with compounded intravitreal bevacizumab. DESIGN: Retrospective chart
      review. PARTICIPANTS: All patients with post-injection endophthalmitis who were
      seen over a 6.5-year period at a tertiary retina referral practice. METHODS: We
      identified all cases of endophthalmitis by searching for patients who received
      intravitreal antibiotics and had antecedent intravitreal injection of
      bevacizumab, ranibizumab, or aflibercept. RESULTS: A total of 54,101 injections
      of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of
      aflibercept were performed. The incidence of suspected endophthalmitis was 0.041%
      (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for
      ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive
      cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02%
      (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for
      aflibercept. There was no statistically significant difference in endophthalmitis
      rate between the 3 different compounded drugs with respect to both overall
      suspected endophthalmitis rate and culture-positive endophthalmitis rate (p =
      0.87). CONCLUSION: Compounding of ranibizumab and aflibercept for intravitreal
      use appears to be safe because the endophthalmitis rate does not appear to be
      different from that of intravitreal bevacizumab.

PMID- 29217034
TI  - Ruptured globe from badminton racquet injury while wearing spectacles.

PMID- 29217035
TI  - Exudative complications following photodynamic therapy.

PMID- 29217036
TI  - Response to "Exudative complications following photodynamic therapy".

PMID- 29217037
TI  - Re: Nutritional optic neuropathy instead of tobacco-alcohol amblyopia.

PMID- 29217038
TI  - Corrigendum to: "Glucose transporter isoform-1 receptor-positive infantile
      capillary hemangiomas: case report and literature review", Canadian Journal of
      Ophthalmology, volume 49 (2014), e156-e158.

PMID- 29217039
TI  - Medical therapy for bilateral uveal effusion syndrome in nanophthalmos.

PMID- 29217040
TI  - Optical coherence tomography angiography imaging of Purtscher retinopathy.

PMID- 29217041
TI  - Bilateral persistent fetal vasculature and a chromosome 10 mutation including
      COX15.

PMID- 29217042
TI  - Transient central retinal artery occlusion following viperine snake bite.

PMID- 29217043
TI  - Retinal detachment and microangiopathy in mitochondrial encephalomyopathy, lactic
      acidosis, and stroke-like episodes syndrome.

PMID- 29217044
TI  - Meesmann epithelial corneal dystrophy: recurrence following photorefractive
      keratectomy.

PMID- 29217045
TI  - Ophthalmoparesis and unilateral finger flexor muscle weakness in seronegative
      myasthenia gravis.

PMID- 29217046
TI  - Anti-NMDA-receptor optic neuritis in a patient with a history of encephalitis.

PMID- 29217047
TI  - Visual worsening despite resolution of subfoveal fluid in nonarteritic ischemic
      optic neuropathy.

PMID- 29217048
TI  - Bilateral inferior hemifield visual loss secondary to a pituitary prolactinoma.

PMID- 29217049
TI  - Bilateral multiple iridociliary cysts in diffuse uveal melanocytic proliferation.

PMID- 29217050
TI  - Sequential development of dermatofibrosarcoma protuberans in the forehead and
      eyelid.

PMID- 29217051
TI  - A primary squamous cell carcinoma of the orbit.

PMID- 29217052
TI  - Acute orbital sarcoidosis with preceding fever and erythema nodosum.

PMID- 29217053
TI  - Squamous cell carcinoma arising from syringocystadenoma papilliferum of the
      eyelid.

PMID- 29217054
TI  - Classification and Pathology of Congenital and Perinatal Vascular Anomalies of
      the Head and Neck.
AB  - Accurate histopathologic description in correlation with clinical and
      radiological evaluation is required for treatment of vascular anomalies, both
      neoplastic and malformative. It is important to examine current clinical,
      histologic, and immunophenotypical features that distinguish the major types of
      congenital and perinatal vascular anomalies affecting the head and neck. General
      discussions of pathogenesis and molecular diagnosis must also be taken into
      account. This article provides an overview of the features that distinguish the
      major types of congenital and perinatal vascular anomalies affecting the head and
      neck, and summarizes the diagnostic histopathologic criteria and nomenclature
      currently applied to these lesions.

PMID- 29217055
TI  - Outcome Measurement for Vascular Malformations of the Head and Neck.
AB  - Vascular malformations are congenital anomalies of the vascular and/or lymphatic
      system that affect the head and neck region. The most common treatment options
      are sclerotherapy, laser therapy, surgery, and embolization. Because vascular
      malformations are variable in type, size, extent, and location, it is a challenge
      to select methods for evaluation of treatment outcome. Without standardized
      outcome reporting, it is difficult to compare and combine scientific evidence to
      support therapeutic decision making. Standardized collection and reporting of
      outcome data are the first steps toward a fair comparison between treatments.
      This article describes outcome measurements for vascular malformations and
      initiatives to improve outcome reporting.

PMID- 29217056
TI  - The Role of Surgery in the Management of Infantile Hemangiomas: What is the Best
      Timing?
AB  - Surgery for the management of infantile hemangiomas has become commonplace.
      Surgical technique articles are plentiful; however, little has been written about
      the timing of surgery. Knowledge of the biology of the tumors, data from
      developmental psychology, and the utility of facial reconstruction provide
      guidelines for timing of surgical intervention.

PMID- 29217057
TI  - The Surgical Management of Infantile Hemangiomas.
AB  - The surgical management of facial infantile hemangiomas presents a unique
      challenge. The aim of the surgeon should be to remove the hemangioma and to
      restore normal facial features. Each of the facial zones has its own special
      features and challenges. The surgeon should remember that the child started out
      with normal anatomy and that as the hemangioma proliferated, it displaced and
      thinned these normal structures and in many cases, expanded adjacent tissue.
      Hemangiomas do not as a rule, invade adjacent tissues as they proliferate. These
      facts will help in planning the various surgical approaches.

PMID- 29217058
TI  - Management of Infantile Hemangiomas of the Airway.
AB  - Infantile hemangiomas (IHs) of the airway are far less common than their
      cutaneous counterparts, and their symptoms mimic those of viral croup. As a
      result, by the time these lesions are diagnosed, they are often advanced and
      causing airway compromise. Fortunately, the evolution of propranolol as an
      effective and safe pharmacotherapy has simplified management of IH and reduced
      the likelihood of complications previously seen with steroid therapy and surgery.
      Nevertheless, the otolaryngologist must be prepared with an alternate plan to
      manage lesions refractory to pharmacotherapy. This article reviews the clinical
      presentation and current management of IHs of the airway.

PMID- 29217059
TI  - New Frontiers in Our Understanding of Lymphatic Malformations of the Head and
      Neck: Natural History and Basic Research.
AB  - The future of head and neck lymphatic malformation (HNLM) evaluation and
      treatment is changing because of 2 decades of clinical research and recent basic
      science investigation. Basic science investigation using cellular biology and
      molecular genetics has revealed the genetic cause of some HNLMs, which has
      created the possibility of medical treatment specific to HNLM. This article
      summarizes the clinical and basic science research that will likely influence the
      future of HNLM assessment and treatment.

PMID- 29217060
TI  - Multidisciplinary Approach to the Management of Lymphatic Malformations of the
      Head and Neck.
AB  - Lymphatic malformations (LMs) occur in 2.8 to 5 per 100,000 live births. Most
      involve the head and neck and they are equally common in men and women. They are
      developmental anomalies of unknown cause, although recent evidence suggests that
      an upregulation of the mammalian target of rapamycin (mTOR) pathway may be a
      causal factor leading to the overproduction of abnormal lymph vessels. These
      vessels are likely dilated lymphatic sacs sequestered from the lymphatic and
      venous systems. This overproduction results in the accumulation of lymph in
      dilated cystic spaces, which in turn results in the clinical features of an LM.

PMID- 29217061
TI  - Venous Malformations of the Head and Neck.
AB  - Venous malformations (VMs) of the head and neck arise from deficits in the
      development of venous network. Clinically, VMs are highly variable, from small
      and asymptomatic varicosities to massive cervicofacial lesions. Therapeutic
      approaches include surgery; laser photocoagulation; sclerotherapy; and, more
      recently, systemic targeted drugs. This article discusses the natural history,
      diagnosis, and management of VMs.

PMID- 29217062
TI  - Arteriovenous Malformations of the Head and Neck.
AB  - Extracranial arteriovenous malformations (AVMs) are complex vascular
      malformations to diagnose and treat. They are comprised of congenitally derived
      arteriovenous shunts with chronic vascular expansion, collateralization, and
      infiltration of local tissue. Their cause remains unclear, but new genetic and
      molecular clues are emerging. They may present at any age following an early
      quiescent period. Diagnosis is based on vascular staining, soft tissue expansion,
      progressive growth, warmth, and pulsations. Focal lesions can be cured, whereas
      diffuse AVMs demonstrate highly recidivistic disease. Multimodal therapy with
      staged interventions can improve treatment outcomes, increase treatment
      intervals, and control disease. Vigilant follow-up is critical.

PMID- 29217063
TI  - Capillary Malformations (Portwine Stains) of the Head and Neck: Natural History,
      Investigations, Laser, and Surgical Management.
AB  - Capillary malformations (CMs), also known as port-wine stains, are the most
      common type of congenital vascular malformations. Facial CM often occurs with a
      quasidermatomal distribution according to the sensory trigeminal nerve
      distribution. With time, these lesions darken progressively, and soft tissue
      hypertrophy, bony hypertrophy, and/or nodule formation can develop. Multiple
      treatments for CM have been reported. However, the mainstay and gold standard
      therapy for facial or aesthetically sensitive CM is still the pulsed dye laser
      treatment. In patients with associated soft tissue/bony hypertrophy, surgical
      management is helpful in restoring the normal anatomy and in re-establishing a
      symmetric contour.

PMID- 29217064
TI  - The Management of Vascular Malformations of the Airway: Natural History,
      Investigations, Medical, Surgical and Radiological Management.
AB  - Vascular malformations may affect nearly all aspects of the upper airway. Each
      type of malformation has a characteristic pattern of disease. These lesions may
      be focal or diffuse, and require directed management strategies. Physicians
      treating these entities should have a high level of suspicion to consider airway
      evaluation even in the absence of overt symptoms. However, cutaneous head and
      neck venous malformations or other lesions affecting the lips, oral cavity, or
      tongue can herald the presence of coexisting airway lesions. A multidisciplinary
      approach is critical in achieving comprehensive treatment.

PMID- 29217065
TI  - Orthognathic Considerations of Vascular Malformations.
AB  - Vascular malformations affect the craniofacial skeleton in many ways, depending
      on the type of the lesion and its location. The lesions may exert a mass effect
      and cause thinning or thickening of the bone or cause expansion from direct bony
      infiltration. Orthognathic surgery can be used to correct any malocclusion or
      open bite deformities after the soft tissues are addressed.

PMID- 29217066
TI  - Hereditary Hemorrhagic Telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) describes the presenting
      manifestations of a disorder that is characterized by pathologic blood vessels.
      HHT is inherited as an autosomal dominant trait with variable penetrance. The
      abnormal vascular structures (dysplasias) can affect all the organs in the human
      body. The link between a physical stimulus and new lesion development has been
      established for mucosal trauma owing to nasal airflow turbulence, for ultraviolet
      exposure to the fingers, and for mechanical trauma to the dominant hand. The
      pressing question then is whether HHT treatment constitutes a stimulus that is
      sufficient to trigger new lesion development.

PMID- 29217067
TI  - Etiology and Genetics of Congenital Vascular Lesions.
AB  - The detection of somatic, activating genetic mutations to underlie development of
      vascular tumors and malformations led to a better understanding of their
      pathophysiology. Proteins encoded by the detected mutated genes activate the two
      major signaling pathways, also involved in cancer: the RAS/MAPK/ERK pathway
      and/or the PI3K/AKT/mTOR pathway. This gives a strong basis for studies to
      repurpose cancer therapeutics to patients with vascular tumors and malformations.

PMID- 29217068
TI  - Imaging of Vascular Lesions of the Head and Neck.
AB  - This article provides an overview of imaging findings of common and uncommon
      vascular lesions in the head and neck and showcases images highlighting imaging
      findings. Both hemangiomas and vascular malformations are covered.

PMID- 29217069
TI  - Infantile Hemangiomas in the Head and Neck Region.
AB  - Infantile hemangiomas (IHs) are benign vascular tumors of infancy most common in
      the region of the head and neck. Infantile hemangiomas are common; but they are
      extremely heterogeneous and cause a range of complications depending on their
      morphology, size, or location. Medical interventions for high-risk patients
      include topical and systemic therapies, including oral propranolol, which has
      revolutionized the management of IHs over the past recent years. In the following
      article, the authors aim to provide a review of the natural history, pathology,
      complications, syndromes, and medical management of infantile hemangioma.

PMID- 29217070
TI  - Congenital Vascular Tumors.
AB  - Vascular tumors are benign neoplasms, which result from proliferating endothelial
      cells. These lesions present during infancy or childhood, may affect any
      location, and exhibit postnatal growth. Local complications include bleeding,
      tissue destruction, and pain whereas systemic sequelae include thrombocytopenia,
      congestive heart failure, and death. Vascular tumors should be differentiated
      from vascular malformations, which present at birth, have a quiescent
      endothelium, and grow in proportion to the child. Together, vascular tumors and
      malformations comprise the field of vascular anomalies.

PMID- 29217072
TI  - Multidisciplinary Approach to Vascular Anomalies Maximizes Outcomes.

PMID- 29217071
TI  - Psychosocial Impact of Vascular Anomalies on Children and Their Families.
AB  - Vascular anomalies are divided into tumors and malformations based on their
      clinical and cytologic attributes. Vascular malformations are further
      subcategorized as low-flow lymphatic, venous, capillary, or mixed lesions and as
      high-flow arteriovenous malformations. Treatment is reserved for vascular
      anomalies that are symptomatic or cosmetically disfiguring, and surgical and
      nonsurgical treatment options are widely varied with variable outcomes.

PMID- 29217073
TI  - Congenital Vascular Lesions of the Head and Neck.

PMID- 29217074
TI  - BIG is beautiful, baby!

PMID- 29217075
TI  - [Study of the reproducibility of the sterilization process and proposal of an
      sterilizer requalification protocol].
AB  - Unlike EN 554, and since the publication of ISO 17665-1 standard, the user of
      autoclaves may use methods other than those indicated in the guidelines.
      Outsourcing the requalification of sterilizers by an external service provider
      and after observing from the previous requalification reports that the
      thermometric data seemed reproducible, we decided to propose and validate a
      validation method for the reproducibility of the sterilization process. This is
      to exempt from the study of the repeatability of the EN 554 standard in future
      requalifications. Reproducibility was studied with the sensors of the
      sterilization service and from the production cycles. This study was carried out
      in three parts. First, we checked whether our sensors were reliable. Then we
      evaluated the sterilization process fidelity of each sterilizer. Finally, we
      compared our measurements performed by the service sensors with the measurements
      performed by the service provider during the requalifications of the previous
      years. This work leads us to describe a new protocol of requalification of our
      sterilizers.

PMID- 29217076
TI  - Pleural effusion in multiple myeloma.

PMID- 29217077
TI  - Validation of the NaURSE rule for predicting in-hospital mortality in
      nonagenarians.

PMID- 29217078
TI  - The clinician and their patient at the end of life.

PMID- 29217079
TI  - Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation
      promoting branching and nephron number.
AB  - The regulation of final nephron number in the kidney is poorly understood.
      Cessation of nephron formation occurs when the self-renewing nephron progenitor
      population commits to differentiation. Transcription factors within this
      progenitor population, such as SIX2, are assumed to control expression of genes
      promoting self-renewal such that homozygous Six2 deletion results in premature
      commitment and an early halt to kidney development. In contrast, Six2
      heterozygotes were assumed to be unaffected. Using quantitative morphometry, we
      found a paradoxical 18% increase in ureteric branching and final nephron number
      in Six2 heterozygotes, despite evidence for reduced levels of SIX2 protein and
      transcript. This was accompanied by a clear shift in nephron progenitor identity
      with a distinct subset of downregulated progenitor genes such as Cited1 and Meox1
      while other genes were unaffected. The net result was an increase in nephron
      progenitor proliferation, as assessed by elevated EdU (5-ethynyl-2'-deoxyuridine)
      labeling, an increase in MYC protein, and transcriptional upregulation of MYC
      target genes. Heterozygosity for Six2 on an Fgf20-/- background resulted in
      premature differentiation of the progenitor population, confirming that
      progenitor regulation is compromised in Six2 heterozygotes. Overall, our studies
      reveal a unique dose response of nephron progenitors to the level of SIX2 protein
      in which the role of SIX2 in progenitor proliferation versus self-renewal is
      separable.

PMID- 29217080
TI  - MEMS gyroscope control using a novel compound robust control.
AB  - This paper proposes a new compound fractional order integral terminal sliding
      mode control (FOITSMC) and proportional-derivative control (PD-FOITSMC) for the
      control of a MEMS gyroscope. In order to improve the robustness of the
      conventional integral terminal sliding mode control (ITSMC), a fractional
      integral terminal sliding mode surface is applied. The chattering problem in
      FOITSMC, which is usually generated by the excitation of fast un-modelled dynamic
      is the main drawback. A PD controller is employed in order to eliminate
      chattering phenomenon. The stability of the PD-FOITSMC is proved by Lyapunov
      theory. The performance of the proposed control method is compared with two other
      controllers such as ITSMC and FOITSMC. Numerical simulations clearly verified the
      effectiveness of the proposed control approach.

PMID- 29217081
TI  - [Zosteriform cutaneous metastasis in melanoma].
AB  - INTRODUCTION: Cutaneous metastases are common in patients with malignant
      melanoma. In rare cases, they are distributed on a dermatome, in which case they
      are known as zosteriform metastases. OBSERVATION: We report the case of a patient
      with zosteriform metastasis of a malignant melanoma, progressing unfavourably
      despite surgical excision and immunotherapy. DISCUSSION: The physiopathology of
      this condition continues to be poorly understood.

PMID- 29217082
TI  - [Prosthetic genioplasty versus osseous genioplasty in aesthetic chin
      augmentation: Literature review and knowledge update].
AB  - Chin augmentation is commonly practiced, whether in microgenia treatment, in
      cases of orthognathic or cosmetic surgery. Located at the crossroads of many
      specialties, the technique choice still differs according to the surgeon
      specialiy. A large number of publications on the subject are available. A
      comparaison between different surgical methods is therefore possible concerning
      their indications and their complication. The purpose of this study was to carry
      out a literature review, with updating knowledge, as well as a synthesis
      indication regarding aesthetic osseous and alloplastic genioplasty. Despite the
      generalization of "modern" implants in France, prosthetic genioplasty remains
      more frequently the source of serious complications (infections, extrusions, bone
      erosions). Similarly, this technique has much more limited indications than
      osseous genioplasty, which has the advantage of a better longevity. In order to
      increase the aesthetic appearance of the chin, osseous genioplasty should be
      performed more easily and more frequently by surgeons on all sides.

PMID- 29217083
TI  - Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck:
      clinical and histopathological analysis.
AB  - Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm of salivary
      gland origin with a low-grade indolent nature. It is difficult to distinguish
      from other malignant salivary gland tumours. Clinical outcomes following surgery
      are generally reported as good. The aim of this study was to further determine
      the features of HCCC. This study was approved by Medical ethics review of
      affiliated hospital of jiangsu university. Fourteen new cases of HCCC are
      reported. The clinical and histopathological data of these 14 cases were analysed
      alongside those of 141 cases identified in a systematic review of the literature
      (up to 2016). Demographic data, histopathological findings, clinical
      presentation, primary treatment, and outcomes were extracted. Histologically,
      HCCC tumour cells had a clear cell morphology with hyalinized stroma.
      Immunohistochemical results were positive for cytokeratins and EMA, but negative
      for SMA, S100, vimentin, and calponin. Twelve of the 14 patients showed EWSR1
      translocation. Local nodal metastasis on presentation was present in 17.3% and
      the overall recurrence rate was 17.7% in the total population (N=155), compared
      with 35.7% and 21.4%, respectively, in the new cases alone. Focal necrosis and
      local metastasis were identified as possibly associated with recurrence. The
      overall prognosis was good: only 3.8% of patients died of the disease. HCCC is
      less indolent than was previously thought, but overall the prognosis is good.
      Risk factors for recurrence may include focal necrosis and local metastasis at
      presentation. The best treatment for patients with HCCC is wide local excision
      combined with regional lymph node dissection.

PMID- 29217084
TI  - Oral phenytoin protects against experimental cyclophosphamide-chemotherapy
      induced hair loss.
AB  - In the current study, effects of oral phenytoin on hair growth in
      cyclophosphamide-treated rats were assessed with the goal of evaluating the
      ability of phenytoin to suppress chemotherapy-induced hair loss. Thirty-six rats
      were randomly assigned to six groups (1k6) of six each (n=6). In all groups,
      anagen was induced in flank skin of rats by depilation. On day 9 (anagen VI),
      rats were injected once with either distilled water (groups 1-3) or
      cyclophoshamide (groups 4-6). From day 10, rats in group 1 and 4 received oral
      vehicle (distilled water), groups 2 and 5 received oral phenytoin (50mg/kg),
      while groups 3 and 6 also received oral phenytoin (100mg/kg). Drug or vehicle was
      administered daily for a period of 28days. The flank area was serially
      photographed. At the end of the experimental period, rats were sacrificed to
      correlate visible hair growth with a histological profile of follicle response
      and recovery. Glutathione (GSH), glutathione peroxidase (GPX) and lipid
      peroxidation status were assessed. Cyclophosphamide (CYP) treatment was
      associated with gross morphologic and histological evidence of hair loss in the
      flanks, microscopic evidence of hair-shaft thinning, increased skin lipid
      peroxidation, decreased GSH level, and reduction in GPX activities. Phenytoin co
      administration was associated with evidence of improved hair growth, increased
      hair-shaft thickness, reduced skin lipid peroxidation, increased GSH level, and
      increased GPX activities. This study showed that oral phenytoin can suppress hair
      loss due to CYP therapy in rats; however, further studies are needed to evaluate
      its potential application in chemotherapy-induced alopecia.

PMID- 29217085
TI  - IgG4-related disease presenting as hoarseness and postcricoid ulcer.

PMID- 29217086
TI  - Effect of inhaled allergens and air pollutants on childhood rhinitis development.

PMID- 29217087
TI  - Evolution of Simplified Frozen Elephant Trunk Repair for Acute DeBakey Type I
      Dissection: Midterm Outcomes.
AB  - BACKGROUND: A modified technique for frozen elephant trunk (FET) repair of acute
      DeBakey type I dissection has evolved. Procedural modifications are described and
      midterm outcomes evaluated. METHODS: From 2009 to 2016, 72 patients with DeBakey
      type I dissection underwent emergency simplified FET. Mean age was 59 +/- 15
      years. Presentation included malperfusion (n = 22, 31%), rupture (n = 12, 16%),
      and aortic insufficiency (n = 42, 58%). Concomitant procedures included valve
      replacement (n = 9), root replacement (n = 11; valve sparing n = 6), cusp repair
      (n = 11), and valve resuspension (n = 21). The first 39 were treated by modifying
      an early generation stent graft. The next 16 received newer modified stent
      grafts, and the latest 17 underwent branched single anastomosis technique with
      left subclavian stent grafting. RESULTS: Operative mortality was 4.2% (n = 3 of
      72). Two presented comatose without recovering, the other died from coagulopathy
      complications. Morbidity included stroke (n = 3, 4.2%), spinal injury (n = 3,
      4.2%; 1 permanent), tracheostomy (n = 7, 9.7%), and renal failure (n = 2, 2.8%).
      Median follow-up was 28 +/- 25 months. Survival was 92% at 6 months, 92% at 1
      year, 89% at 3 years, and 80% at 5 years. Among 69 survivors, follow-up imaging
      was available in 63 (91%). Of these, 58 (92%) patients thrombosed the treated
      false lumen, with shrinkage in 37(54%) patients from 42 +/- 8 mm to 37 +/- 7 mm.
      Ten patients underwent 14 late reinterventions for growth and incomplete
      thrombosis (7 endo extension, 4 left subclavian embolization, 1 bypass, 2 false
      lumen embolization). Freedom from reintervention was 93% at 6 months, 87% at 1
      year, 77% at 3 years, and 72% at 5 years. CONCLUSIONS: Simplified FET for
      treating acute DeBakey type I dissection has evolved and remained safe. It
      promotes aortic remodeling, and simplifies management of chronic aortic
      complications.

PMID- 29217089
TI  - Fully-coupled mathematical modeling of actomyosin-cytosolic two-phase flow in a
      highly deformable moving Keratocyte cell.
AB  - Interaction between intracellular dynamics and extracellular matrix (ECM)
      generally occurred into very thin fragment of moving cell, namely lamellipodia,
      enables all movable cells to crawl on ECM. In fast-moving cells such as fish
      Keratocytes, Lamellipodia including most cell area finds a fan-like shape during
      migration, with a variety of aspect ratio function of fish type. In this work,
      our purpose is to present a novel and more complete two-dimensional continuum
      mathematical model of actomyosin-cytosolic two-phase flow of a self-deforming
      Keratocyte with circular spreaded to steady fan-like shape. In the new approach,
      in addition to the two-phase flow of the F-actin and cytosol, the G-actin
      transport was spatiotemporally modeled. We also for the first time modeled the
      effect of variable volume fraction of the moving F-actin porous network on solute
      transport in the cytosolic fluid. Our novel fully-coupled mathematical model
      provides a better understanding of intracellular dynamics of fast-migrating
      Keratocytes; such as the F-actin centripetal and cytosolic fountain-like flows,
      free-active myosin distribution, distribution sequence of the G-actin, F-actin,
      and myosin, and myosin-induced pressure flied of cytoplasm as well as the map of
      intracellular forces like myosin contraction and adhesion traction. All these
      results are qualitatively and quantitatively in good agreement with experimental
      observations. According to a range of value of parameters used in this model, our
      steady state of moving Keratocyte finds fan-like shape with the same aspect ratio
      as wide category of fish Keratocytes. This new model can predict shape of
      Keratocytes in other range of parameter values.

PMID- 29217088
TI  - Induction Cisplatin Docetaxel Followed by Surgery and Erlotinib in Non-Small Cell
      Lung Cancer.
AB  - BACKGROUND: Data from meta-analyses support the use of induction or adjuvant
      platinum-based chemotherapy for locally advanced non-small cell lung cancers
      (NSCLCs). This phase 2 study assessed the role of induction cisplatin and
      docetaxel followed by surgery in patients with resectable stage I to III NSCLCs,
      followed by 12 months of adjuvant erlotinib. METHODS: Patients with resectable
      stage I to III NSCLCs received cisplatin 80 mg/m2, docetaxel 75 mg/m2 every 21
      days for 3 cycles, followed by surgery, followed by adjuvant erlotinib for 12
      months. The primary endpoint included safety. Long-term efficacy outcomes and
      exploratory analysis of intermediary endpoints are also reported (NCT00254384).
      RESULTS: Forty-seven eligible patients received a median of 3 cycles of induction
      treatment, 37 underwent surgical resection, and only 21 received adjuvant
      erlotinib. Two patients died in the perioperative period (1 sepsis during
      chemotherapy, 1 acute respiratory distress syndrome postoperatively). Most common
      grade 3 to 5 toxicities during chemotherapy included hypokalemia (8%), infection
      (7%), and granulocytopenia (25%). During adjuvant erlotinib, 14% of patients
      experienced grade 2 rash. Median overall survival was 3.4 years. Major pathologic
      responses in the primary tumor were observed in 19% (7 of 37) of patients and
      correlated with improved long-term overall survival. Complete pathologic response
      in mediastinal/hilar nodes also correlated with superior survival. CONCLUSIONS:
      Induction cisplatin and docetaxel was well tolerated. Adjuvant erlotinib did not
      improve outcomes compared with historical controls. Major pathologic response
      predicted for improved long-term survival and is a suitable intermediary endpoint
      for future phase 2 studies.

PMID- 29217090
TI  - Walking speed differentially alters spinal loads in persons with traumatic lower
      limb amputation.
AB  - Persons with lower limb amputation (LLA) perceive altered motions of the
      trunk/pelvis during activities of daily living as contributing factors for low
      back pain. When walking (at a singular speed), larger trunk motions among persons
      with vs. without LLA are associated with larger spinal loads; however, modulating
      walking speed is necessary in daily life and thus understanding the influences of
      walking speed on spinal loads in persons with LLA is of particular interest here.
      Three-dimensional trunk-pelvic kinematics, collected during level-ground walking
      at self-selected (SSW) and two controlled speeds (~1.0 and ~1.4 m/s), were
      obtained for seventy-eight participants: 26 with transfemoral and 26 with
      transtibial amputation, and 26 uninjured controls (CTR). Using a kinematics
      driven, non-linear finite element model of the lower back, the resultant
      compressive and mediolateral/anteroposterior shear loads at the L5/S1 spinal
      level were estimated. Peak values were extracted and compiled. Despite walking
      slower at SSW speeds (~0.21 m/s), spinal loads were 8-14% larger among persons
      with transfemoral amputation vs. CTR. Across all participants, peak compressive,
      mediolateral, and anteroposterior shear loads increased with increasing walking
      speed. At the fastest (vs. slowest) controlled speed, these increases were
      respectively 24-84% and 29-77% larger among persons with LLA relative to CTR.
      Over time, repeated exposures to these increased spinal loads, particularly at
      faster walking speeds, may contribute to the elevated risk for low back pain
      among persons with LLA. Future work should more completely characterize relative
      risk in daily life between persons with vs. without LLA by analyzing additional
      activities and tissue-level responses.

PMID- 29217091
TI  - Microstructural changes associated with osteoporosis negatively affect loading
      induced fluid flow around osteocytes in cortical bone.
AB  - Loading-induced interstitial fluid flow in the microporosities of bone is
      critical for osteocyte mechanotransduction and for the maintenance of tissue
      health, enhancing convective transport in the lacunar-canalicular system. In
      recent studies, our group has reported alterations of bone's vascular porosity
      and lacunar-canalicular system microarchitecture in a rat model of postmenopausal
      osteoporosis. In this work, poroelastic finite element analysis was used to
      investigate whether these microstructural changes can affect interstitial fluid
      flow around osteocytes. Animal-specific finite element models were developed
      combining micro-CT reconstructions of bone microstructure and measures of the
      poroelastic material properties. These models were used to quantify and compare
      loading-induced fluid flow in the lacunar-canalicular system of ovariectomized
      and sham-operated rats. A parametric analysis was also used to quantify the
      influence of the lacunar-canalicular permeability and vascular porosity on the
      fluid velocity magnitude. Results show that mechanically-induced interstitial
      fluid velocity can be significantly reduced in the lacunar-canalicular system of
      ovariectomized rats. Interestingly, the vascular porosity is shown to have a
      major influence on interstitial fluid flow, while the lacunar-canalicular
      permeability influence is limited when larger than 10-20m2. Altogether our
      results suggest that microstructural changes associated with the osteoporotic
      condition can negatively affect interstitial fluid flow around osteocytes in the
      lacunar-canalicular system of cortical bone. This fluid flow reduction could
      impair mechanosensation of the osteocytic network, possibly playing a role in the
      initiation and progression of age-related bone loss and postmenopausal
      osteoporosis.

PMID- 29217092
TI  - MRI-based experimentations of fingertip flat compression: Geometrical
      measurements and finite element inverse simulations to investigate material
      property parameters.
AB  - Modeling human-object interactions is a necessary step in the ergonomic
      assessment of products. Fingertip finite element models can help investigating
      these interactions, if they are built based on realistic geometrical data and
      material properties. The aim of this study was to investigate the fingertip
      geometry and its mechanical response under compression, and to identify the
      parameters of a hyperelastic material property associated to the fingertip soft
      tissues. Fingertip compression tests in an MRI device were performed on 5
      subjects at either 2 or 4 N and at 15 degrees  or 50 degrees . The MRI images
      allowed to document both the internal and external fingertip dimensions and to
      build 5 subject-specific finite element models. Simulations reproducing the
      fingertip compression tests were run to obtain the material property parameters
      of the soft tissues. Results indicated that two ellipses in the sagittal and
      longitudinal plane could describe the external fingertip geometry. The internal
      geometries indicated an averaged maximal thickness of soft tissues of 6.4 +/- 0.8
      mm and a 4 +/- 1 mm height for the phalanx bone. The averaged deflections under
      loading went from 1.8 +/- 0.3 mm at 2 N, 50 degrees  to 3.1 +/- 0.2 mm at 4 N, 15
      degrees . Finally, the following set of parameters for a second order
      hyperelastic law to model the fingertip soft tissues was proposed: C01=0.59 +/-
      0.09 kPa and C20 = 2.65 +/- 0.88 kPa. These data should facilitate further
      efforts on fingertip finite element modeling.

PMID- 29217093
TI  - Risk factors for the appearance of secondary foci of infection in children with
      community-acquired Staphylococcus aureus bacteraemia. Cohort study 2010-2016.
AB  - INTRODUCTION: Community-acquired Staphylococcus aureus (SA) bacteraemia is a
      common cause of hospitalisation in children. The occurrence of secondary foci
      (SF) of SA infection is associated with higher morbidity and mortality.
      OBJECTIVES: To identify risk factors for SF of infection in children with
      community-acquired SA bacteraemia. MATERIAL AND METHODS: Prospective cohort. All
      children aged from 30 days to 16 years admitted to a paediatric referral hospital
      between January 2010 and December 2016 for community-acquired infections, with SA
      isolated in blood cultures, were included. Microbiological, demographic and
      clinical characteristics were compared, with or without SF infection after
      72hours of hospitalisation. RESULTS: A total of 283 patients were included, 65%
      male (n=184), with a median age of 60 months (IQR: 30-132). Seventeen per cent
      (n=48) had at least one underlying disease and 97% (n=275) had some clinical
      focus of infection, the most common being: osteoarticular 55% (n=156) and soft
      tissue abscesses 27% (n=79). A total of 65% (n=185) were resistant to
      methicillin. A SF of infection was found in 16% of patients (n=44). The SF
      identified were pneumonia 73% (n=32), osteoarticular 11% (n=5), soft tissue 11%
      (n=5) and central nervous system 5% (n=2). In the multivariate analysis, the
      persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07
      5.37, P<0.001) and sepsis (OR: 17.23, 95%CI 5.21-56.9, P<0.001) were predictors
      of SF. There was no association with methicillin sensitivity. CONCLUSIONS: In
      this cohort, methicillin-resistant SA infections predominated. The occurrence of
      SF of infection was associated with the persistence of bacteraemia after the
      fifth day and sepsis on admission.

PMID- 29217094
TI  - Treatment of infections caused by nontuberculous mycobacteria.
AB  - Nontuberculous mycobacteria are a heterogeneous group of microorganisms that can
      often cause human infection, although they may also be considered to be
      contaminants or colonisers on occasions. The management of these infections must
      necessarily take into account the identification of isolated species and their in
      vitro susceptibility testing (although not for all of them), as well as the
      characteristics of the patient, because these treatments are usually prolonged
      and must be carried out by experts in the management of these infections.
      Classically divided into slowly growing mycobacteria and rapidly growing
      mycobacteria, the treatment regimens and the antibiotics used are different for
      both groups. In addition, in certain circumstances, this treatment must
      necessarily be linked to other measures (removal of foreign bodies, surgery) in
      order to maximise the likelihood of curing the patient.

PMID- 29217095
TI  - Sofosbuvir plus daclatasvir as an alternative for patients on haemodialysis with
      genotype 2 hepatitis C virus infection.

PMID- 29217096
TI  - Trend and seasonality of community-acquired Escherichia coli antimicrobial
      resistance and its dynamic relationship with antimicrobial use assessed by ARIMA
      models.
AB  - INTRODUCTION: We studied the trend and seasonality of community-acquired
      Escherichia coli resistance and quantified its correlation with the previous use
      of certain antibiotics. METHODS: A time series study of resistant community
      acquired E. coli isolates and their association with antibiotic use was conducted
      in a Primary Health Care Area from 2008 to 2012. A Poisson regression model was
      constructed to estimate the trend and seasonality of E. coli resistance. RESULTS:
      A significant increasing trend in mean E. coli resistance to cephalosporins,
      aminoglycosides and nitrofurantoin was observed. Seasonal resistance to
      ciprofloxacin and amoxicillin-clavulanic acid was significantly higher in autumn
      winter. There was a delay of 7, 10 and 12 months between the use of cotrimoxazole
      (P<0.038), fosfomycin (P<0.024) and amoxicillin-clavulanic acid (P<0.015),
      respectively, and the occurrence of E. coli resistance. CONCLUSIONS: An average
      delay of 10 months between the previous use of amoxicillin-clavulanic acid,
      cotrimoxazole and fosfomycin and the appearance of resistant community-acquired
      E. coli strains was detected.

PMID- 29217097
TI  - Ocular Manifestations of Familial Transthyretin Amyloidosis.

PMID- 29217098
TI  - Prolonged Time Lag to Final Diagnosis of Fragile X Syndrome.
AB  - OBJECTIVE: To evaluate the diagnostic process in children ultimately diagnosed
      with fragile X syndrome (FXS), with an emphasis on the time lag between initial
      presentation and on diagnosis in female vs male children. STUDY DESIGN:
      Interviews were conducted with 89 families of children with a final diagnosis of
      FXS and assessment of time intervals between initial presentation and confirmed
      molecular diagnosis. RESULTS: Screening of 117 patients (25 female patients) from
      the 89 families revealed that less than 20% of patients obtained a diagnosis
      within the first year of seeking medical attention. Mean age at the time of
      initial presentation was 12.3 months in male patients and 23 months in female
      patients, while definitive diagnosis of FXS was made at a mean of 4 and 9 years,
      respectively. Presenting symptoms of developmental delays were recognized by 72%
      of parents, and 84% had another child with FXS before the index case diagnosis.
      Average age of diagnosis for children with FXS born since 2007 was significantly
      lower at 31.9 months, compared with 69.5 months for children born before 2007.
      CONCLUSIONS: Although FXS is a significant and prevalent cause of disability in
      children, it is underdiagnosed and diagnosed late, especially in female patients.
      In every male and female patient presenting with developmental delay or autism,
      FXS should be considered. Dysmorphic physical features may not be present in
      infancy, and the absence of those features cannot exclude a diagnosis of FXS.

PMID- 29217099
TI  - Proinflammatory Diets during Pregnancy and Neonatal Adiposity in the Healthy
      Start Study.
AB  - OBJECTIVE: To evaluate the association between dietary inflammatory index (DII)
      scores during pregnancy and neonatal adiposity. STUDY DESIGN: The analysis
      included 1078 mother-neonate pairs in Healthy Start, a prospective prebirth
      cohort. Diet was assessed using repeated 24-hour dietary recalls. DII scores were
      obtained by summing nutrient intakes, which were standardized to global means and
      multiplied by inflammatory effect scores. Air displacement plethysmography
      measured fat mass and fat-free mass within 72 hours of birth. Linear and logistic
      models evaluated the associations of DII scores with birth weight, fat mass, fat
      free mass, and percent fat mass, and with categorical outcomes of small- and
      large-for-gestational age. We tested for interactions with prepregnancy BMI and
      gestational weight gain. RESULTS: The interaction between prepregnancy BMI and
      DII was statistically significant for birth weight, neonatal fat mass, and
      neonatal percent fat mass. Among neonates born to obese women, each 1-unit
      increase in DII was associated with increased birth weight (53 g; 95% CI, 20,
      87), fat mass (20 g; 95% CI, 7-33), and percent fat mass (0.5%; 95% CI, 0.2-0.8).
      No interaction was detected for small- and large-for-gestational age. Each 1-unit
      increase in DII score was associated a 40% increase in odds of a large-for
      gestational age neonate (1.4; 95% CI, 1.0-2.0; P = .04), but not a small-for
      gestational age neonate (1.0; 95% CI, 0.8-1.2; P = .80). There was no evidence of
      an interaction with gestational weight gain. CONCLUSIONS: Our findings support
      the hypothesis that an increased inflammatory milieu during pregnancy may be a
      risk factor for neonatal adiposity. TRIAL REGISTRATION: Clinicaltrials.gov:
      NCT02273297.

PMID- 29217100
TI  - Childhood Corporal Punishment and Future Perpetration of Physical Dating
      Violence.
AB  - OBJECTIVE: To test whether experiencing childhood corporal punishment is linked
      to later perpetration of dating violence. STUDY DESIGN: Young adults (n = 758;
      61% female; mean age of 20 years), originally recruited for a longitudinal study
      as 9th- and 10th-grade Texas high school students, were asked about their
      childhood experiences with corporal punishment and physical abuse, as well as
      current experiences with dating violence. A path model was used to determine
      whether childhood corporal punishment was related to recent perpetration of
      physical dating violence, while controlling for childhood physical abuse, age,
      sex, ethnicity, and socioeconomic status. RESULTS: In all, 19% of participants (n
      = 134) reported physical dating violence perpetration and 68% reported
      experiencing corporal punishment as children (n = 498). Analysis showed a
      significant positive association between corporal punishment and physical
      perpetration of dating violence (OR 1.30, 95% CI 1.07-1.59). Even after
      controlling for sex, ethnicity, age, parental education, and child physical
      abuse, childhood corporal punishment was associated significantly with physical
      dating violence perpetration (aOR 1.29, 95% CI 1.02-1.62). CONCLUSIONS: The
      finding that childhood corporal punishment was associated with perpetration of
      young adult physical dating violence, even after controlling for several
      demographic variables and childhood physical abuse, adds to the growing
      literature demonstrating deleterious outcomes associated with corporal
      punishment.

PMID- 29217101
TI  - A Novel In Situ Simulation Intervention Used to Mitigate an Outbreak of
      Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit.
AB  - OBJECTIVE: To describe the successful implementation of an in situ simulation
      program to diagnose and correct latent safety threats in a level 4 neonatal
      intensive care unit (NICU) to mitigate a methicillin-resistant Staphylococcus
      aureus (MRSA) outbreak. STUDY DESIGN: An investigational report describes a
      simulation intervention that occurred during a 4-month MRSA outbreak in a single
      center, 46-bed, newly renovated level 4 NICU. The simulation program was
      developed for all NICU providers in which they were exposed to a 30-minute in
      situ human simulation intervention that included education, evaluation, and
      debriefing to resolve perceived or observed latent safety threats. The primary
      study outcome was improved hand hygiene compliance and an enhanced estimate of
      the culture of safety during a 6-month period. RESULTS: A total of 99 healthcare
      providers including physicians, nurses, respiratory therapists, and environmental
      service workers completed the course. Before the simulation intervention, there
      were 18 patients colonized or infected with a single MRSA clone; after the
      intervention, there were no new episodes of colonization or infection.
      CONCLUSIONS: An in situ, simulation-based intervention can counter threats to
      patient safety related to workflow and lapses in infection control practices and
      improve patient outcomes.

PMID- 29217102
TI  - Papular Purpuric Gloves and Socks Syndrome because of a Mycoplasma Infection.

PMID- 29217103
TI  - Coming to Terms with Cardiovascular Morbidity after Early Term Birth.

PMID- 29217104
TI  - [Does tocilizumab mean the end of glucocorticoids in giant cell arteritis?]

PMID- 29217105
TI  - Influence of muscle strength on early mobility in critically ill adult patients:
      Systematic literature review.
AB  - BACKGROUND: Muscle strength may be one indicator of readiness to mobilize that
      can be used to guide decisions regarding early mobility efforts and to
      progressively advance mobilization. OBJECTIVES: To provide a synthesis of current
      measures of muscle strength in the assessment of early mobilization in critically
      ill adult patients who are receiving MV therapy. METHODS: Research studies
      conducted between 2000-2015 were identified using PubMed, CINHAL, MEDLINE, and
      the Cochrane Database of Systematic Reviews databases using the search terms
      "muscle strength", "intensive care", "mechanical ventilation" and "muscle
      weakness". RESULTS: Nine articles used manual muscle testing, the Medical
      Research Council scale and/or hand-held dynamometer to provide objective measures
      for assessing muscle strength in the critically ill adult patient population.
      CONCLUSIONS: Further research is needed to examine the application of
      standardized measures of muscle strength for guiding decisions regarding early
      and progressive advancement of mobility goals in adult ICU patients on MV.

PMID- 29217106
TI  - A novel mortality prediction model for the current population in an adult
      intensive care unit.
AB  - BACKGROUND: The accurate and reliable mortality prediction is very useful, in
      critical care medicine. There are various new variables proposed in the
      literature that could potentially increase the predictive ability for death in
      ICU of the new predictive scoring model. OBJECTIVE: To develop and validate a new
      intensive care unit (ICU) mortality prediction model, using data that are
      routinely collected during the first 24 h of ICU admission, and compare its
      performance to the most widely used conventional scoring systems. METHODS:
      Prospective observational study in a medical/surgical, multidisciplinary ICU,
      using multivariate logistic regression modeling. The new model was developed
      using data from a medical record review of 400 adult intensive care unit patients
      and was validated on a separate sample of 36 patients, to accurately predict
      mortality in ICU. RESULTS: The new model is simple, flexible and shows improved
      performance (ROC AUC = 0.85, SMR = 1.25), compared to the conventional scoring
      models (APACHE II: AUC = 0.76, SMR = 2.50, SAPS III: AUC = 0.76, SMR = 1.50), as
      well as higher predictive capability regarding ICU mortality (predicted
      mortality: 41.63 +/- 31.61, observed mortality: 41.67%). CONCLUSION: The newly
      developed model is a quite simple risk-adjusted outcome prediction tool based on
      12 routinely collected demographic and clinical variables obtained from the
      medical record data. It appears to be a reliable predictor of ICU mortality and
      is proposed for further investigation aiming at its evaluation, validation and
      applicability to other ICUs.

PMID- 29217107
TI  - The underlying physiological basis of the desert rodent Meriones shawi's survival
      to prolonged water deprivation: Central vasopressin regulation on peripheral
      kidney water channels AQPs-2.
AB  - Meriones shawi (M. shawi) is a particular semi-desert rodent known by its
      resistance to long periods of thirst. The aim of the present investigation is to
      clarify the underlying mechanisms allowing M. shawi to resist to hard conditions
      of dehydration. For this reason we used two different approaches: i) a
      morphometric study, which consists in measuring the effect of dehydration on body
      and kidneys weights as well as the report kidney weight/body weight, ii) By
      immunohistochemistry, we proceed to study the effect of dehydration on the
      immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2)
      which is a channel protein that allows water to permeate across cell membranes.
      Our results showed both a body mass decrease accompanied by a remarkable kidneys
      hypertrophy. The immunohistochemical study showed a significant increase of AQP-2
      immunoreactivity in the medullar part of Meriones kidneys allowing probably to
      Meriones a great ability to water retention. Consistently, we demonstrate that
      the increased AQP-2 expression occurred together with an increase in vasopressin
      (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular
      nucleus (PVN), which are a major hub in the osmotic control circuitry. These
      various changes seen either in body weight and kidneys or at the cellular level
      might be the basis of peripheral control of body water homeostasis, providing to
      M. shawia strong resistance against chronic dehydration.

PMID- 29217108
TI  - Improved outcomes after heart transplantation for cardiac amyloidosis in the
      modern era.
AB  - BACKGROUND: Cardiac amyloidosis, caused most commonly by deposition of light
      chain (AL) or transthyretin (ATTR) type fibrils, has an extremely poor prognosis.
      In this retrospective single-center study, we evaluated temporal trends in
      survival after heart transplantation for cardiac amyloidosis. METHODS: We
      analyzed 48 patients with cardiac amyloidosis (AL, n = 32; familial ATTR, n = 16)
      who underwent heart transplantation from May 2002 to March 2017. Patients were
      analysed in 2 periods, Era 1 (2002- 2007) and Era 2 (2008- 2017), separated by
      altered patient selection in both, AL and ATTR amyloidosis, and changed
      chemotherapy regimens for AL amyloidosis. RESULTS: The modern era was
      characterized by a lower number of extracardiac organ involvement for AL (94%
      isolated cardiac amyloidosis in Era 2 vs 56% in Era 1; p = 0.0221), and more
      frequent treatment for AL with the proteasome inhibitor bortezomib (94% in Era 2
      vs 6% in Era 1; p < 0.0001). AL patients had significantly lower survival than
      patients with non-amyloid cardiomyopathy after heart transplantation in Era 1,
      and ATTR patients had numerically lower survival. However, survival in the modern
      era was comparable to non-amyloid transplants in both cohorts, possibly
      reflecting a shift in chemotherapy strategies and patient selection,
      respectively. CONCLUSIONS: In the current era, use of enhanced chemotherapy
      regimens for isolated advanced AL cardiac amyloidosis was associated with
      outcomes comparable to non-amyloid cardiomyopathy. We conclude that heart
      transplantation in highly selected patients with isolated non-systemic advanced
      cardiac amyloidosis may be a feasible approach.

PMID- 29217109
TI  - High prevalence of skin cancers and actinic keratoses in lung transplant
      recipients.

PMID- 29217110
TI  - End-stage renal disease after pediatric heart transplantation: A 25-year national
      cohort study.

PMID- 29217111
TI  - Tackling the challenge of multi-morbidity: Actions for health policy and
      research.

PMID- 29217112
TI  - Assessment of left atrial function by three-dimensional speckle-tracking in
      cardiomyopathies: A step forward?

PMID- 29217113
TI  - Simultaneous determination of borate, chloride and molybdate in pyrohydrolysis
      distillates of plant and soil samples by ion chromatography.
AB  - Determination of concentrations of micronutrients in plant samples is important
      in order to assess the growth and quality of plants. An ion chromatography (IC)
      method was developed for the simultaneous determination of B, Cl and Mo
      (micronutrients present in their anionic form in aqueous samples) using a
      gradient elution with d-mannitol and NaOH. Despite their different chemical
      nature, these elements could be separated from the matrix by employing
      pyrohydrolysis. IC was employed for their sequential determination from single
      aliquot injection into the IC column. It was observed that the optimised
      procedures developed earlier in our laboratory for the separation of B and
      halogens using d-Mannitol-NaOH or bicarbonate eluents could not be extended to B
      Mo-Cl separation. The concentration levels of d-mannitol in the eluent required
      for separation of boron impeded the conductivity detection of Mo and the peak
      sensitivity was seen to be critically dependent on d-mannitol concentration in
      the eluent. In addition, d-mannitol in NaOH eluent altered the retention times of
      analytes (B, F-, Cl-, NO3-, SO42-and MoO42-) which were not observed in the case
      of bicarbonate eluent. The current study deals with the investigation on the
      influence of d-mannitol on the molybdate as well as its role on the retention
      time. Formation of Mo-mannitol complex at different pH conditions and de
      protonation of mannitol were correlated to the observed effects. Based on the
      observations, a gradient elution method was proposed for the simultaneous
      separation and determination of B, Cl and Mo in the pyrohydrolysis distillates of
      plant samples. The method was calibrated for B (0.05-1 mg/L), Cl (0.1-10 mg/L)
      and Mo (0.5-10 mg/L) and the linear regression coefficients obtained were 0.9992,
      0.9998 and 0.997 respectively. The limit of detection (LOD) for B, Cl and Mo was
      calculated to be 19, 23 and 96 MUg/L, respectively. The developed IC method after
      pyrohydrolytic separation of B, Cl and Mo was successfully applied for the
      analysis of real samples.

PMID- 29217114
TI  - Identification of bacterial uropathogens by preparative isoelectric focusing and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - This study describes a new method for simultaneous identification of uropathogens
      in the case of polybacterial urinary tract infections. The method utilizes
      recently developed preparative isoelectric focusing (IEF) in cellulose-based
      separation medium with a subsequent analysis by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
      Preparative IEF was successfully used for both purification and separation of
      bacteria, Escherichia coli (pI 4.6) and Staphylococcus aureus (pI 3.4), in urine
      samples. The focused zones of bacteria, localized by the positions of focused
      colored pI markers, were easily collected from the separation media after the IEF
      analysis and then unambiguously identified by MALDI-TOF MS. The proposed method
      enables the identification of bacteria in urine specimens when the concentration
      of individual bacteria is >=104 cells mL-1. Another benefit is the viability of
      bacteria extracted from the collected fractions after preparative IEF.

PMID- 29217115
TI  - [Psychosomatic symptoms as an expression of the deterioration of the health
      related quality of life in adolescents].
AB  - AIM: To analyze, in a population of adolescents in school, the relationship
      between psychosomatic symptoms and the perception of health-related quality of
      life (HRQoL), differentiating by gender and age group. DESIGN: Transversal study.
      LOCATION: Five Secondary Schools. PARTICIPANTS: Eight hundred and forty four
      adolescents between the ages of 15 and 18 in secondary school. MAIN MEASUREMENTS:
      HRQoL using KIDSCREEN-52 and psychosomatic symptoms with the psychosomatic
      problems scale (PSP). RESULTS: Girls and adolescents aged 17-18 years presented
      significantly higher psychosomatic symptoms, both groups also scored worse in all
      dimensions of HRQoL, although only the dimensions related to physical and mental
      wellness, mood and stress reached significance. All psychosomatic symptoms were
      inversely associated with the ten dimensions of KIDSCREEN-52. The regression
      models showed that sadness, concentrating difficulties and sleeping difficulties
      were the predictors of worse HRQoL in both sexes and age groups and these
      variables explained between 30 and 41% of the HRQoL variance of the adolescents.
      CONCLUSIONS: Psychosomatic symptoms are frequent especially in girls and in older
      adolescents and predictors of worse HRQoL. It is important to distinguish them
      from medical conditions to avoid unnecessary interventions. As expressions of
      emotional discomfort they must be evaluated and treated in an integral way
      because they interfere with daily life and increase the vulnerability proper of
      adolescence.

PMID- 29217116
TI  - [Surveillance of antibiotic consumption in Spain: The importance of the DHD
      indicator].

PMID- 29217117
TI  - Age of majority assessment in Dutch individuals based on Cameriere's third molar
      maturity index.
AB  - Radiological examination of the third molar is done in living individuals for
      estimation of chronological age, especially in the late adolescence. The aim of
      this study was to assess the application of Cameriere's third molar maturity
      index (I3M) to determine whether an individual is 18 years or older (adult) or
      younger than 18 years (minor) in a sample of Dutch individuals. The sample
      consisted of panoramic images of 360 individuals aged between 14 and 22 years
      old. Three observers performed the measurements. Gender was not statistically
      significant in discriminating adults and minors. The highest value of the Youden
      index of the receiver operating curve analysis was for the value of I3M<0.08 in
      discriminating individuals as minor or adult. The specificity (Sp) and
      sensitivity (Se) results for females were 96.3% and 72.7% respectively. The Sp
      and Se for males were 95.0% and 84.0% respectively. The probabilities of
      correctly classified individuals were 83.3% and 88.9%, and Bayes post-test
      probability was 96.3% and 95.7% in females and males respectively. Obtained
      results showed that the specific cut-off point of I3M<0.08 may be a useful and
      reliable method for adult age assessment in a Dutch population.

PMID- 29217118
TI  - Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer.
AB  - Tumor necrosis factor (TNF) is a proinflammatory cytokine that coordinates tissue
      homeostasis by regulating cytokine production, cell survival, and cell death.
      However, how life and death decisions are made in response to TNF is poorly
      understood. Many inflammatory pathologies are now recognized to be driven by
      aberrant TNF-induced cell death, which, in most circumstances, depends on the
      kinase Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Recent
      advances have identified ubiquitin (Ub)-mediated phosphorylation of RIPK1 as
      belonging to crucial checkpoints for cell fate in inflammation and infection. A
      better understanding of these checkpoints might lead to new approaches for the
      treatment of chronic inflammatory diseases fueled by aberrant RIPK1-induced cell
      death, and/or reveal novel strategies for anticancer immunotherapies, harnessing
      the ability of RIPK1 to trigger immunogenic cell death.

PMID- 29217120
TI  - Hydric environmental effects on turtle development and sex ratio.
AB  - Experimental and field studies of different turtle species suggest that moisture
      influences embryonic development and sex ratios, wetter substrates tend to
      produce more males, and drier substrates produce more females. In this study, we
      used Trachemys scripta elegans to test the effect of moisture on embryonic
      development and sex ratios. T. s. elegans eggs were incubated under different
      temperature and moisture regimes. We monitored embryonic development until stage
      22 (after sex determination) and, for the first time, we estimated sex ratios
      using a male-specific transcriptional molecular marker, Sox9. Among treatments,
      we found differences in developmental rates, egg mass, and sex ratio. Embryos
      developed slowly in cooler and wetter sand substrate while water uptake by the
      eggs was significantly greater on wetter substrates. Developmental differences
      were due to moisture interacting with temperature where increased water content
      of the sand resulted in temperatures that were 2-3 degrees C lower than air
      temperatures. The coolest and the wettest substrates produced 100% males compared
      to 42% males from the warmest and driest treatment. Further, we found that
      embryonic growth appears to be more sensitive to temperature at earlier stages of
      development and to moisture at later stages. This study shows how moisture may
      change the incubation conditions inside nests by changing the temperature
      experienced by eggs, which affects development, growth and sex ratios. The
      results of this study highlight the importance of including moisture conditions
      when predicting embryo growth and sex ratios and in developing proxies of
      embryonic development.

PMID- 29217121
TI  - Diagnostic and treatment effects of sialendoscopy for patients with swelling of
      the parotid gland when sialoliths are undetected with computed tomography.
AB  - Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery.
      32 patients had parotid gland disease and 9 patients had intermittent swelling of
      the parotid gland and sialoliths were not detected with CT imaging. 4 patients
      were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly
      confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was
      unable to be inserted in the other 2 patients, who had stenosis of the orifice of
      the Stensen's duct. Balloon expansion of the duct was performed in these 2
      patients and a steroid drug was injected into the duct in one patient. Complete
      remission was archived in one patient treated with sialendoscopy. Three patients
      had sialolithiasis. Microsialoliths and/or white floating matter was observed and
      removed using sialendoscopy. All patients experienced complete remission. In
      cases of Sjogren syndrome and recurrent parotitis, sialendoscopic surgery was
      performed, but the symptoms showed no improvement. For patients with
      microsialoliths, sialendoscopy may be most useful for diagnosis and treatment
      when the sialoliths are not detected with CT imaging. At present, sialendoscopic
      surgery have limitation in the treatment of Stensen's duct stenosis and may
      similarly have limitation in the treatment of Sjogren's syndrome and recurrent
      parotitis.

PMID- 29217119
TI  - Panomics for Precision Medicine.
AB  - Medicine is poised to undergo a digital transformation. High-throughput platforms
      are creating terabytes of genomic, transcriptomic, proteomic, and metabolomic
      data. The challenge is to interpret these data in a meaningful manner - to
      uncover relationships that are not readily apparent between molecular profiles
      and states of health or disease. This will require the development of novel data
      pipelines and computational tools. The combined analysis of multi-dimensional
      data is referred to as 'panomics'. The ultimate hope of integrative panomics is
      that it will lead to the discovery and application of novel markers and targeted
      therapeutics that drive forward a new era of 'precision medicine' where inter
      individual variation is accounted for in the treatment of patients.

PMID- 29217122
TI  - Phase I-III development of the EORTC QLQ-ANL27, a health-related quality of life
      questionnaire for anal cancer.
AB  - BACKGROUND AND PURPOSE: There is currently no health-related quality of life
      (HRQoL) measure specific to anal cancer. Our objective was to develop an anal
      cancer HRQoL module to supplement the EORTC QLQ-C30 questionnaire using EORTC
      Quality of Life Group Guidelines. MATERIALS AND METHOD: In order to generate a
      list of HRQoL issues facing anal cancer patients treated with chemoradiotherapy
      (CRT), we systematically reviewed the literature and conducted semi-structured
      interviews with patients and health care professionals (HCPs). Our list was then
      operationalised into questions using the EORTC Item Library. The provisional
      question list was pilot tested alongside the EORTC QLQ-C30 with patients from 11
      centres across 8 countries. RESULTS: From our literature review and interviews
      with 43 patients, we generated a list of 197 issues. The list was then refined to
      134 issues and reviewed by 34 HCPs and 10 patients. This review resulted in the
      retention of 65 issues which were used in the draft questionnaire tested by 100
      patients. Our analyses led to the modification and removal of questions resulting
      in a 27 item questionnaire, the EORTC QLQ-ANL27. CONCLUSION: We have developed a
      27 item questionnaire to supplement the EORTC QLQ-C30, for use with patients
      treated for anal cancer. This has been pilot tested and is now available upon
      request for use in clinical trials as well as clinical practice in 8 languages
      (http://groups.eortc.be/qol/).

PMID- 29217123
TI  - Food Insecurity and the Nutrition Care Process: Practical Applications for
      Dietetics Practitioners.

PMID- 29217124
TI  - Analysis of the mixing performance of a full-scale membrane bioreactor for
      municipal wastewater treatment.
AB  - High energy consumption remains to be a key problem for application of membrane
      bioreactor (MBR). Optimization of MBR to save energy requires a compressive
      understanding of the performance of the reactor, among which the mixing
      performance is a significant parameter, however received little attention. In
      this study, a tracer experiment was carried out in a full-scale MBR for municipal
      wastewater treatment in China. The mixing performance of both the entire plant
      and the membrane tanks were evaluated. The entire plant was found to be a cascade
      of 2.15 continuous stirred tank reactors (CSTRs) with 8.02% of dead zones. The
      membrane tanks were also found to deviate from CSTR. The mixing energy was
      analyzed and compared with literature data from three aspects: the specific power
      used per unit of tank volume (Ps,v), per unit of permeate volume (Ps,p), and per
      unit of membrane area (Ps,m).

PMID- 29217125
TI  - Designing a CO2 supply strategy for microalgal biodiesel production under diurnal
      light in a cylindrical-membrane photobioreactor.
AB  - A cylindrical membrane photobioreactor with high CO2 mass transfer coefficient
      was designed and installed under customized unidirectional lighting.
      Combinatorial effect of light and CO2 on the growth of Chlorella sp. FC2 IITG was
      studied and an optimal CO2 supply without pH control strategy was developed under
      diurnal light similar to sunlight (17-2000-17 uE m-2 s-1). Unprecedentedly, broad
      range of saturated light levels (700-1500 uE m-2 s-1), reversible
      photoinhibition, no pH control requirement and dark-phase growth were noticed
      altogether in the strain. Under diurnal light, final biomass titer of 5.79 g L-1
      and overall biomass productivity of 1.29 g L-1 day-1 were observed. The results
      were similar to optimal light (1130 uE m-2 s-1) and CO2 (2%) conditions.
      Subsequently, a highest FAME productivity of 265 mg L-1 day-1 was observed in
      last two days of lipid induction phase.

PMID- 29217126
TI  - Fast protocol for the production of Histoplasma capsulatum antigens for antibody
      detection in the immunodiagnosis of histoplasmosis.
AB  - BACKGROUND: Current methods for the production of Histoplasma capsulatum antigens
      are problematic in terms of standardization, specificity, stability,
      repeatability and reproducibility. AIMS: In this study, we sought to optimize the
      methodology for producing H. capsulatum antigens, and to evaluate its
      applicability. METHODS: Antigenic preparations obtained from 12 H. capsulatum
      isolates were evaluated by double immunodiffusion and immunoblotting assays
      against homologous and heterologous sera. RESULTS: The evaluated and optimized
      protocol allowed a more stable production, as well as repeatable, reproducible,
      with shorter culture time and less costly. By double immunodiffusion and
      immunoblotting assays, the best pattern of reactivity was observed for antigens
      obtained with 33 days of culture from the isolates 200 and 406 against the M
      antigen and for the isolate 200 with 15 days against H antigen. The SDS-PAGE
      presented antigenic components of molecular masses between 17 and 119kDa. The
      immunoblotting sensitivity was 95.5% and 100% with histoplasmosis sera from ill
      patients and sera from H. capsulatum infected but otherwise healthy patients,
      respectively, to the antigen derived from isolates 200 and 406. CONCLUSIONS: We
      suggest the employment of the antigen from isolate 200, with 15 or 30 days of
      culture, in the double immunodiffusion and immunoblotting assays due to its good
      ability to discriminate both sera from patients with histoplasmosis illness and
      histoplasmosis infection, in addition to its high specificity against
      heterologous sera.

PMID- 29217127
TI  - Epigenome in Early Mammalian Development: Inheritance, Reprogramming and
      Establishment.
AB  - Drastic epigenetic reprogramming takes place during preimplantation development,
      leading to the conversion of terminally differentiated gametes to a totipotent
      embryo. Deficiencies in remodeling of the epigenomes can cause severe
      developmental defects, including embryonic lethality. However, how chromatin
      modifications and chromatin organization are reprogrammed upon fertilization in
      mammals has long remained elusive. Here, we review recent progress in
      understanding how the epigenome is dynamically regulated during early mammalian
      development. The latest studies, including many from genome-wide perspectives,
      have revealed unusual principles of reprogramming for histone modifications,
      chromatin accessibility, and 3D chromatin architecture. These advances have shed
      light on the regulatory network controlling the earliest development and maternal
      zygotic transition.

PMID- 29217128
TI  - Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis.
AB  - There is growing interest in exploring circulating (plasma/serum) irisin in
      polycystic ovary syndrome (PCOS) patients. This meta-analysis aimed to summarize
      the evidence assessing circulating irisin changes in this population. A
      systematic search was conducted in three databases: PubMed, Cochrane Library and
      Web of Science, for studies reporting irisin in PCOS patients compared with
      healthy controls or stratified by body mass index (BMI), or assessing irisin
      response to hyperinsulinemia. Effect sizes (Cohen's d with 95% confidence
      intervals [CI]) were calculated using random-effects models. Eight studies with
      918 PCOS patients and 528 healthy controls were included. Results showed that
      circulating irisin was higher in PCOS patients than in overall healthy controls
      (d = 0.37, 95% CI 0.05 to 0.70), but not compared with BMI-matched or age- and
      BMI-matched controls. Circulating irisin was higher in PCOS patients with higher
      BMI than lower (d = 0.36, 95% CI 0.16 to 0.56). Circulating irisin decreased 2 h
      later in response to euglycemic hyperinsulinemia in PCOS patients with a larger
      magnitude than healthy controls (d = -0.32, 95% CI -0.53 to -0.11). In summary,
      with adjustment for BMI, circulating irisin in PCOS patients seems comparable to
      healthy controls, but its response to hyperinsulinemia might be impaired.

PMID- 29217129
TI  - Long alimentary limb duodenal switch (LADS): a short-term prospective randomized
      trial.
AB  - BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the
      most effective bariatric surgeries, in terms of weight loss and remission of co
      morbidities. It is however associated with a significant risk of protein and
      nutritional deficiency, as well as gastrointestinal side effects. OBJECTIVES: To
      assess the effect of increasing the strict alimentary limb on weight loss,
      nutritional deficiency and quality of life, compared with standard BPD-DS.
      SETTINGS: University-affiliated tertiary care center. METHODS: Prospective
      randomized double blind (patient-evaluator) trial in which patients were assigned
      in a 1:1 ratio to undergo a modified BPD-DS with a long alimentary limb (1 m from
      Treitz ligament, n = 10) or a standard biliopancreatic diversion (strict
      alimentary limb of 1.5 m, n = 10). Common channel was kept at 100 cm in both
      groups. Follow-up at 12 months was completed in all patients. RESULTS: Initial
      weight (126 +/- 10 versus 125 +/- 17, P = .92), age (40 +/- 7 versus 37 +/- 8, P
      = .35), and sex ratio (1 female/9 males) were similar in both groups. Excess
      weight loss and total weight loss were significantly higher in the standard BPD
      DS group (93.4 +/- 12% versus 73.3 +/- 7%, P = .0007 and 46 +/- 5.6% versus 37 +/
      3.4%, P = .0004). The study group had significantly higher vitamin D, manganese,
      and copper levels at 12 months. Both groups had similar drop in glycated
      hemoglobin, cholesterol levels, and resolution of co-morbidities at 12 months.
      Long alimentary limb was associated with significantly less bowel movements a day
      (1.6 +/- .97 versus 2.55 +/- 1.01, P = .01), less gastrointestinal side effects
      (bloating and gas, P<.05) and required less pancreatic enzymes supplements (0
      versus 40%, P = .04) and calcium supplement. Quality of life was significantly
      improved in both groups in all domains (all P<.05). CONCLUSION: At 12 months,
      weight loss was lesser in the long alimentary limb group. There was however no
      difference in the remission of co-morbidities and higher levels of vitamin D,
      manganese, and copper. Gastrointestinal adverse effects and the need for
      pancreatic enzymes were less with similarly excellent quality of life at 12
      months. Longer follow-up is necessary to evaluate long-term weight loss and
      nutritional deficiencies.

PMID- 29217130
TI  - Resected gastric volume has no influence on early weight loss after laparoscopic
      sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a popular procedure
      for treatment of obesity, but it is still undecided whether resected gastric
      volume (RGV) is related to weight loss after LSG. OBJECTIVE: The aim of this
      study was to investigate the influence of RGV and other factors on weight loss at
      1 year after LSG in a Chinese population. SETTING: University Hospital, China.
      METHODS: A total of 53 patients who underwent LSG between August 2015 and July
      2016 were enrolled. The LSG procedure and RGV measurement were performed using
      standardized techniques. Patients were followed-up every 3 months in the first
      year and 6 monthly after that. Correlations between the percentage of excess
      weight loss at 1 year (%EWL-1 yr) and RGV and other parameters were evaluated.
      RESULTS: All patients completed at least 1 year of follow-up. No major
      complications or cases of underweight were seen. Mean body mass index (BMI) at 1
      year after LSG was significantly lower than the baseline BMI (31.1 +/- 3.8 kg/m2
      versus 39.0 +/- 6.6 kg/m2; P<.001). Mean %EWL-1 yr was 58.8%, and mean RGV was
      862.6 +/- 209.5 mL. No correlation was observed between %EWL-1 yr and RGV (r = 
      0.071; P = .613). The %EWL-1 yr was correlated with preoperative weight, BMI,
      RGV/weight, and RGV/BMI. RGV was positively correlated with preoperative weight
      and BMI. Patients who achieved satisfactory weight loss (%EWL >=50%) had
      significantly lower baseline BMI, and higher RGV/weight and RGV/BMI, than those
      who had inadequate weight loss. However, RGV was not significantly different
      between the 2 groups. CONCLUSIONS: Weight loss effect at 1 year after LSG was not
      associated with RGV in this Chinese population. RGV was influenced by the weight
      and BMI.

PMID- 29217131
TI  - Omega-loop gastric bypass is more effective for weight loss but negatively
      impacts liver enzymes: a registry-based comprehensive first-year analysis.
AB  - BACKGROUND: The impact of omega-loop gastric bypass (OLGB) on weight loss and
      liver enzymes remains inconclusive. OBJECTIVE: The aim of this study was to
      compare the impact of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB),
      and OLGB on weight loss and liver enzyme levels. SETTING: National Bariatric
      Surgery Registry. METHODS: The study included 10,675 cases of SG, 1590 cases of
      RYGB, and 469 cases of OLGB that had available baseline and 1-year (12 +/- 2 mo)
      follow-up data. RESULTS: The highest percentage of excess weight loss was
      achieved by the OLGB group (84.5% +/- 26.7%), followed by the SG (78.5% +/-
      26.0%) and RYGB (72.0% +/- 26.5%) groups (P<.05). The data show that 10% of OLGB
      cases, 5.2% of RYGB cases, and 1.9% of SG cases (P<.001) had increases in alanine
      aminotransferase levels, from a normal baseline mean of 23.9 +/- 7.5 U/L to an
      abnormal mean of 64.8.7 +/- 66.0 U/L, at follow-up. Similar trends were observed
      for aspartate aminotransferase and alkaline phosphatase. A regression analysis
      showed that OLGB was a predictive risk factor for normal baseline alanine
      aminotransferase levels becoming abnormal postoperatively compared with SG (odds
      ratio [OR] = 5.65) or RYGB (OR = 2.08) (P<.001). Similarly, OLGB was a predictive
      risk factor for baseline aspartate aminotransferase and alkaline phosphatase
      levels becoming abnormal postoperatively. Female sex was the only other
      meaningful predictive risk of alanine aminotransferase (OR = 2.45) and aspartate
      aminotransferase (OR = 1.82) becoming abnormal postoperatively. CONCLUSION: This
      study confirmed the strengths of OLGB weight loss outcomes but also demonstrated
      its negative impact on liver enzymes. Thus, patients and caregivers should be
      informed of the risks, and close follow-up is warranted.

PMID- 29217132
TI  - Mobile phone sensors and supervised machine learning to identify alcohol use
      events in young adults: Implications for just-in-time adaptive interventions.
AB  - BACKGROUND: Real-time detection of drinking could improve timely delivery of
      interventions aimed at reducing alcohol consumption and alcohol-related injury,
      but existing detection methods are burdensome or impractical. OBJECTIVE: To
      evaluate whether phone sensor data and machine learning models are useful to
      detect alcohol use events, and to discuss implications of these results for just
      in-time mobile interventions. METHODS: 38 non-treatment seeking young adult heavy
      drinkers downloaded AWARE app (which continuously collected mobile phone sensor
      data), and reported alcohol consumption (number of drinks, start/end time of
      prior day's drinking) for 28days. We tested various machine learning models using
      the 20 most informative sensor features to classify time periods as non-drinking,
      low-risk (1 to 3/4 drinks per occasion for women/men), and high-risk drinking
      (>4/5 drinks per occasion for women/men). RESULTS: Among 30 participants in the
      analyses, 207 non-drinking, 41 low-risk, and 45 high-risk drinking episodes were
      reported. A Random Forest model using 30-min windows with 1day of historical data
      performed best for detecting high-risk drinking, correctly classifying high-risk
      drinking windows 90.9% of the time. The most informative sensor features were
      related to time (i.e., day of week, time of day), movement (e.g., change in
      activities), device usage (e.g., screen duration), and communication (e.g., call
      duration, typing speed). CONCLUSIONS: Preliminary evidence suggests that sensor
      data captured from mobile phones of young adults is useful in building accurate
      models to detect periods of high-risk drinking. Interventions using mobile phone
      sensor features could trigger delivery of a range of interventions to potentially
      improve effectiveness.

PMID- 29217133
TI  - Prostaglandin E2 suppresses human group 2 innate lymphoid cell function.
AB  - BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are involved in the initial
      phase of type 2 inflammation and can amplify allergic immune responses by
      orchestrating other type 2 immune cells. Prostaglandin (PG) E2 is a bioactive
      lipid that plays protective roles in the lung, particularly during allergic
      inflammation. OBJECTIVE: We set out to investigate how PGE2 regulates human ILC2
      function. METHODS: The effects of PGE2 on human ILC2 proliferation and
      intracellular cytokine and transcription factor expression were assessed by means
      of flow cytometry. Cytokine production was measured by using ELISA, and real-time
      quantitative PCR was performed to detect PGE2 receptor expression. RESULTS: PGE2
      inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5
      and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a
      combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore,
      PGE2 downregulated the expression of IL-2 receptor alpha (CD25). In line with
      this observation, PGE2 decreased ILC2 proliferation. These effects were mediated
      by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors,
      which were specifically expressed on ILC2s. CONCLUSION: Our findings reveal that
      PGE2 limits ILC2 activation and propose that selective EP2 and EP4 receptor
      agonists might serve as a promising therapeutic approach in treating allergic
      diseases by suppressing ILC2 function.

PMID- 29217134
TI  - Reirradiation with concurrent bevacizumab for recurrent high-grade gliomas in
      adult patients.
AB  - PURPOSE: To analyse feasibility, prognostic factors and patterns of recurrence
      after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas.
      PATIENTS AND METHODS: Between 2009 and 2015, 35 patients (median 57-year-old; 21
      men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included
      in this retrospective and consecutive single-centre study. All patients received
      bevacizumab (median number of treatments: 12) concomitant with reirradiation
      (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22
      months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy).
      RESULTS: The median follow-up was 9.2 months from reirradiation. The median
      overall survival from reirradiation was 10.5 months (95% confidence interval [95%
      CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7
      months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was
      44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported.
      Prognostic factors significantly correlated with better overall survival in
      univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003),
      and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty
      two patients bevacizumab-naive at time of reirradiation had a significantly
      increased overall survival from reirradiation compared to patients treated with
      reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P<0.001) as well as
      overall survival from initial diagnosis (58.9 vs. 33.5 months, P=0.006). This
      outcome was similar in patients with initial glioblastomas (P=0.018) or
      anaplastic gliomas (P=0.021). There was no correlation between overall survival
      and gross tumour volume or planning target volume, frontal localization, or
      number of salvage therapies before reirradiation (P>0.05). CONCLUSIONS:
      Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows
      encouraging results in terms of survival and toxicities. Our data suggest that
      reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least
      50Gy.

PMID- 29217136
TI  - "Is it Sjogren's syndrome or burning mouth syndrome? Distinct pathoses with
      similar oral symptoms"-a commentary.

PMID- 29217135
TI  - MicroRNA-145 Impedes Thrombus Formation via Targeting Tissue Factor in Venous
      Thrombosis.
AB  - Venous thromboembolism (VTE), the third leading cardiovascular complication,
      requires more understanding at molecular levels. Here, we have identified miR-145
      as a key molecule for regulating thrombus formation in venous thrombosis (VT)
      employing network based bioinformatics approach and in vivo experiments. Levels
      of miR-145 showed an inverse correlation with thrombus load determined by
      coagulation variables. MiRNA target prediction tools and in vitro study
      identified tissue factor (TF) as a target gene for miR-145. The restoration of
      miR-145 levels in thrombotic animals via in vivo miR-145 mimic delivery resulted
      in decreased TF level and activity, accompanied by reduced thrombogenesis. MiR
      145 levels were also reduced in VT patients and correlated with increased TF
      levels in patients, thereby, confirming our preclinical findings. Our study
      identifies a previously undescribed role of miRNA in VT by regulating TF
      expression. Therefore, restoration of miR-145 levels may serve as a promising
      therapeutic strategy for management of VT.

PMID- 29217137
TI  - Atorvastatin affects negatively respiratory function of isolated endothelial
      mitochondria.
AB  - The purpose of this research was to elucidate the direct effects of two popular
      blood cholesterol-lowering drugs used to treat cardiovascular diseases,
      atorvastatin and pravastatin, on respiratory function, membrane potential, and
      reactive oxygen species formation in mitochondria isolated from human umbilical
      vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not
      significantly affect endothelial mitochondria function. In contrast, hydrophobic
      calcium-containing atorvastatin induced a loss of outer mitochondrial membrane
      integrity, an increase in hydrogen peroxide formation, and reductions in maximal
      (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative
      phosphorylation efficiency. The atorvastatin-induced changes indicate an
      impairment of mitochondrial function at the level of ATP synthesis and at the
      level of the respiratory chain, likely at complex I and complex III. The
      atorvastatin action on endothelial mitochondria was highly dependent on calcium
      ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of
      calcium ions included in atorvastatin molecule induced mitochondrial uncoupling
      that enhanced the inhibition of the mitochondrial respiratory chain by
      atorvastatin. Our results indicate that hydrophobic calcium-containing
      atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative
      action on isolated endothelial mitochondria.

PMID- 29217138
TI  - Durable remission for a woman with refractory choriocarcinoma treated with anti
      endoglin monoclonal antibody and bevacizumab: A case from the New England
      Trophoblastic Disease Center, Brigham and Women's Hospital and Dana-Farber Cancer
      Institute.
AB  - A 36-year-old with metastatic and refractory choriocarcinoma following single-
      and multi-agent chemotherapy and surgical metastectomy experienced a durable
      remission after receiving therapy with an anti-endoglin monoclonal antibody and
      bevacizumab. Treatment options and scientific advances in this disease are
      highlighted.

PMID- 29217139
TI  - ER and PR expression and survival after endometrial cancer.
AB  - OBJECTIVE: To measure association between endometrial carcinoma ER and PR status
      and endometrial cancer (EC) survival, accounting for inter-observer variation.
      METHODS: The intensity and proportion of tumor cell expression of ER and PR in
      ECs were assessed independently and semi-quantitatively by two pathologists using
      digital images of duplicate tumor tissue microarrays (TMAs). Cases with
      inconsistent initial assessment were reviewed and final scoring agreed. The
      association between overall and EC-specific survival and hormone receptor
      expression (intensity, proportion and combined) was assessed using Cox regression
      analysis. The C-index was used to evaluate model discrimination with addition of
      ER and PR status. RESULTS: Tumor ER and PR analysis was possible in 659 TMAs from
      255 patients, and in 459 TMAs from 243 patients, respectively. Initial ER and PR
      scoring was consistent in 82% and 80% of cases, respectively. In multivariate
      analyses decreased ER and PR expression was associated with increased tumor
      related mortality. Associations reached statistical significance for ER
      proportion score (P=0.05), ER intensity score (P=0.003), and PR combined score
      (P=0.04). Decreased expression of combined ER/PR expression was associated with
      poorer EC-specific survival than decreased expression of either hormone receptor
      alone (P=0.005). However, hormone receptor status did not significantly improve
      mortality prediction in individual cases. CONCLUSION: ER and PR expression
      combined, using cut-points that capture variation in scoring and across cores, is
      significantly associated with EC-specific survival in analyses adjusting for
      known prognostic factors. However, at the individual level, ER and PR expression
      does not improve mortality prediction.

PMID- 29217140
TI  - Inhibition of canonical WNT signaling pathway by beta-catenin/CBP inhibitor ICG
      001 ameliorates liver fibrosis in vivo through suppression of stromal CXCL12.
AB  - Quiescent hepatic stellate cells (HSCs), in response to liver injury, undergo
      characteristic morphological transformation into proliferative, contractile and
      ECM-producing myofibroblasts. In this study, we investigated the implication of
      canonical Wnt signaling pathway in HSCs and liver fibrogenesis. Canonical Wnt
      signaling pathway activation and inhibition using beta-catenin/CBP inhibitor
      ICG001 was examined in-vitro in TGFbeta-activated 3T3, LX2, primary human HSCs,
      and in-vivo in CCl4-induced acute liver injury mouse model. Fibroblasts
      conditioned medium studies were performed to assess the Wnt-regulated paracrine
      factors involved in crosstalk between HSCs-macrophages and HSCs-endothelial
      cells. Canonical Wnt signaling pathway components were significantly up-regulated
      in-vitro and in-vivo. In-vitro, ICG-001 significantly inhibited fibrotic
      parameters, 3D-collagen contractility and wound healing. Conditioned medium
      induced fibroblasts-mediated macrophage and endothelial cells activation was
      significantly inhibited by ICG-001. In-vivo, ICG-001 significantly attenuated
      collagen accumulation and HSC activation. Interestingly, ICG-001 drastically
      inhibited macrophage infiltration, intrahepatic inflammation and angiogenesis. We
      further analyzed the paracrine factors involved in Wnt-mediated effects and found
      CXCL12 was significantly suppressed both in-vitro and in-vivo following Wnt
      inhibition. Wnt-regulated CXCL12 secretion from activated HSCs potentiated
      macrophage infiltration and activation, and angiogenesis. Pharmacological
      inhibition of canonical Wnt signaling pathway via suppression of stromal CXCL12
      suggests a potential therapeutic approach targeting activated HSCs in liver
      fibrosis.

PMID- 29217141
TI  - Psychometric properties of the Chinese version of the Dutch Eating Behavior
      Questionnaire in a sample of Taiwanese parents.
AB  - The Dutch Eating Behavior Questionnaire (DEBQ) appraises overeating styles that
      may contribute to weight gain in adults. The purpose of this analysis was to
      assess the psychometric properties of a Chinese version of the DEBQ (C-DEBQ) in a
      sample of parents of school-age children in Taiwan. The C-DEBQ encompassing three
      subscales that including emotional eating, external eating, and restrained
      eating. Each subscale's reliability was assessed with Cronbach's alpha internal
      consistency. Confirmatory factor analysis (CFA) was conducted to validate the
      model fit. A total of 340 normal weight and overweight parents of school-age
      children from various geographical locations in Taiwan participated in the study.
      Each subscale, emotional, external, and restrained eating, displayed good-to
      excellent internal consistency (Cronbach's alphas: .94, .81, and .89,
      respectively). CFA showed that the three-factor solution had close goodness-of
      fit to the data for supporting the factorial validity (x2=1239.03, df=488,
      p<.001, x2/df=2.54, root mean square error of approximation=.067, comparative fit
      index=.879, Tucker-Lewis index=.869). Findings suggest that the C-DEBQ is a
      psychometrically reliable and valid instrument with the potential to assess
      overeating styles in Taiwanese parents of school-age children. Replication
      studies with more age- and gender-diverse populations are needed to provide
      further evidence of construct validity for the Chinese version of the DEBQ.

PMID- 29217142
TI  - Pharmacist-led depression screening and intervention in an underserved, rural,
      and multi-ethnic diabetic population.
AB  - OBJECTIVES: To test the feasibility of implementation and integration of
      community pharmacist-led depression screening for patients with diabetes in an
      underserved rural area and to assess the response rate of prescribers to
      pharmacist-led depression screening and treatment recommendation. SETTING:
      Independent community pharmacy-run diabetes education center. PRACTICE
      DESCRIPTION: Clinical community pharmacy site on Maryland's Eastern Shore.
      PRACTICE INNOVATION: All patients with uncontrolled diabetes (A1C >7%) 18 years
      of age and older attending one or both diabetes self-management classes and
      diabetic counseling completed the Patient Health Questionnaire 9 (PHQ-9). Those
      with moderate to severe cognitive impairment or preexisting mental illness except
      for anxiety or untreated/undertreated depression were excluded from the results.
      A copy of the screening was faxed to the referring provider with an accompanying
      letter. Positive screening reports included a suggestion for further evaluation
      and possible pharmacologic treatment. EVALUATION: Data collected (PHQ-9 scores,
      provider response rate, and A1C) were analyzed with the use of appropriate
      evaluation tools. RESULTS: Of the 57 patients who took the screening, 11 (19.3%)
      were positive and 46 (80.7%) negative for possible depression. Responses were
      received from providers on 3 of the 11 patients who screened positive, and no
      providers initiated depression treatment. The site plans to continue data
      collection following this residency's completion to assess clinical impact.
      CONCLUSION: This model may be replicated at many community pharmacies to
      integrate a depression screening. Based on prescribers' response rate, faxing
      alone is not recommended as the primary communication with the provider, and an
      alternate method should be assessed to effectively recommend pharmacologic
      therapy for patients with positive depression screenings.

PMID- 29217143
TI  - Team work and collaborative practice agreements among pharmacists and nurse
      practitioners.
AB  - OBJECTIVES: The authors share their knowledge about partnering and establishing
      collaborative practice agreements with nurse practitioners. State laws and
      regulations were reviewed that affect pharmacists' ability to fully partner with
      nurse practitioners. SUMMARY: Nurse practitioners' role in primary care is
      growing, and, in many states, nurse practitioners practice independently.
      Collaborative practice agreements (CPAs) enable pharmacists to work with
      prescribers more efficiently. Pharmacists' and nurse practitioners' scope-of
      practice laws and regulations may prevent CPAs between pharmacists and nurse
      practitioners. State pharmacy practice acts were reviewed to demonstrate which
      states allow for partnership under a CPA. CONCLUSION: Pharmacists should consider
      opportunities to partner more closely with nurse practitioners to provide care,
      sometimes under a CPA. In states where laws or regulations prevent CPAs between
      pharmacists and nurse practitioners, pharmacists should advocate for policy
      change.

PMID- 29217144
TI  - Histatin-5 induces the reversal of Pdr5p mediated fluconazole resistance in
      Saccharomyces cerevisae.
AB  - BACKGROUND: Candidiasis is a major opportunistic fungal infection in humans. The
      low number of antifungal drugs available to treat Candida infections and the
      increasing incidence of multidrug resistant (MDR) strains point to an urgent need
      of identifying new therapeutic options. The role of salivary components can
      provide insights for the development of new methodologies of control. OBJECTIVE:
      The aim of this study was to evaluate the ability of histatin-5, a constitutive
      immunological peptide present in saliva, in reversing fungal MDR phenotype, using
      a resistant Saccharomyces cerevisiae strain as model of study. RESULTS: A total
      of 2.5MUg and 5MUg of histatin-5 revealed to be able to chemosensitize (to revert
      antifungal resistance) a MDR strain to fluconazole impairing its intrinsic
      resistance. The presence of histatin-5 decreased the strain growth when
      associated to fluconazole, and also assisted in the retention of rhodamine 6G
      within cell cytoplasm. The ATPase activity of Pdr5p, an ABC efflux transporter,
      was significantly reduced up to 65% within physiological concentration of the
      peptide. CONCLUSION: Results revealed that histatin-5 is able to revert MDR
      phenotype and may be considered a potential alternative MDR inhibitor. Since
      Pdr5p is homologous to Candida albicans CaCdr1p and CaCdr2p, data obtained might
      be extrapolated to these transporters, inferring that associating fluconazole and
      histatin-5 may be a useful tool to circumvent failure treatments of infections
      caused by Candida MDR strains.

PMID- 29217145
TI  - Neurodevelopmental synaptopathies: Insights from behaviour in rodent models of
      synapse gene mutations.
AB  - The genomic revolution has begun to unveil the enormous complexity and
      heterogeneity of the genetic basis of neurodevelopmental disorders such as such
      epilepsy, intellectual disability, autism spectrum disorder and schizophrenia.
      Increasingly, human mutations in synapse genes are being identified across these
      disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis
      pathways as a convergence point underlying disease mechanisms. Here, we review
      some of the key pre- and postsynaptic genes in which penetrant human mutations
      have been identified in neurodevelopmental disorders for which genetic rodent
      models have been generated. Specifically, we focus on the main behavioural
      phenotypes that have been documented in these animal models, to consolidate our
      current understanding of how synapse genes regulate key behavioural and cognitive
      domains. These studies provide insights into better understanding the basis of
      the overlapping genetic and cognitive heterogeneity observed in
      neurodevelopmental disorders.

PMID- 29217146
TI  - The association between adherence to a Mediterranean style diet and cognition in
      older people: The impact of medication.
AB  - BACKGROUND: Recent reviews indicate that adherence to a Mediterranean diet may be
      associated with better cognitive functioning. In assessing these relationships in
      older individuals, previous studies have not taken into account medication usage
      that may support or compromise cognitive functioning. OBJECTIVE: To investigate
      the association between adherence to a Mediterranean style diet, cognition and
      medication usage in cognitively healthy older individuals. DESIGN: Data were
      assessed from individuals aged 60-90 years (mean = 77.8 years, SD = 6.7) from 15
      independent living aged care villages around Melbourne, Australia. Participants'
      diets were assessed using a food frequency questionnaire (FFQ). Cognition was
      assessed using reaction times from the Swinburne University Computerised
      Cognitive Assessment Battery (SUCCAB). Prescribed medications were recorded and
      analysed using binary measures. Cluster analyses were used to group participants
      in terms of cognitive measures and medications taken. Analyses controlled for
      age, gender, average daily kilojoule (kJ) intake and medication cluster. RESULTS:
      The relationship between cognitive speed clusters and medication clusters was
      significant (Chi-squared = 10.63, df = 3, p = 0.014). The odds ratio of 1.533 for
      average daily food intake suggested that for each additional kilojoule of average
      daily intake, the odds of belonging to the slower reaction time cluster increased
      by 53% and odds ratio of 0.573 for Mediterranean diet score suggested that for
      every additional unit, the odds of belonging to the slower reaction time cluster
      declined by 43%. The relationship between Mediterranean diet score and cognition
      was only significant when medication use was taken into account. CONCLUSION:
      These data demonstrate that when medications are considered, a higher
      Mediterranean diet score is associated with a faster response on cognitive
      function tests. The present findings also indicate that it is pertinent to take
      into account medication use when investigating relationships between dietary
      status and cognitive performance.

PMID- 29217147
TI  - A Study of the Natural History of Vitreomacular Traction Syndrome by OCT.
AB  - PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS)
      in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case
      series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS
      with no other ocular comorbidity. METHODS: Patients with VMTS were identified
      from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and
      patient notes were reviewed over a minimum period of 6 months. Data collected
      included patient demographics, best-corrected visual acuity, and OCT features of
      vitreomacular adhesion. Contingency tests and binary logistic modeling were used
      to identify baseline predictors of stability and progression. MAIN OUTCOME
      MEASURES: The rates of spontaneous resolution (defined by release of traction),
      progression to full-thickness macular hole, and surgical intervention were
      analyzed. RESULTS: Presenting visual acuity was 0.3+/-0.3 logMAR units. The mean
      length of follow-up was 17.4+/-12.1 months. During this period, VMTS persisted in
      60% and resolved in 20% (occurring on average at 15 months). Of the remainder,
      12% developed a macular hole and 8% elected to proceed with surgery for symptoms.
      Focal adhesion <1500 MUm was present in 87%. A premacular membrane with macular
      pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal
      thickness remained unchanged. The relative risk of resolution increased in those
      cases with better presenting visual acuities, lesser foveal thicknesses, and no
      associated PMMs; vision significantly improved in those cases with resolution.
      CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual
      acuities did not deteriorate significantly over the study period unless patients
      developed a full-thickness macular hole or required surgical intervention for
      symptoms. Resolution spontaneously occurred in 20%, with an improvement in
      vision.

PMID- 29217148
TI  - Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy:
      The Singapore Epidemiology of Eye Diseases Study.
AB  - PURPOSE: To evaluate the prevalence and risk factors for diabetic retinopathy
      (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. DESIGN:
      Population-based, cross-sectional study. PARTICIPANTS: Persons of Malay, Indian,
      and Chinese ethnicity aged 40+ years, living in Singapore. METHODS: Diabetes was
      defined as nonfasting plasma glucose >=200 mg/dl (11.1 mmol/l), glycated
      hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the
      use of glucose-lowering medication. Retinal photographs, were graded for the
      presence and severity of DR using the modified Airlie House classification
      system. MAIN OUTCOME MEASURES: Diabetic retinopathy, diabetic macular edema
      (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of
      severe nonproliferative or proliferative DR, or clinically significant macular
      edema (CSME). RESULTS: Of the 10 033 subjects, 2877 (28.7%) had diabetes and
      gradable photographs for analysis. The overall age-standardized prevalence (95%
      confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for
      DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR
      (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P = 0.012); a similar trend was
      noted for any DME (P = 0.001) and CSME (P = 0.032). Independent risk factors for
      any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs.
      Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR,
      1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per
      mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg).
      Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase),
      total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low
      density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l
      increase) were associated with lower odds of any DR. Risk factors were largely
      similar across the 3 ethnic groups. CONCLUSIONS: Indian Singaporeans have a
      higher prevalence of DR and DME compared with Chinese and Malays. Major risk
      factors for DR in this study were similar across the 3 ethnic groups. Addressing
      these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.

PMID- 29217149
TI  - Mucous Membrane Pemphigoid with Ocular Involvement: The Clinical Phenotype and
      Its Relationship to Direct Immunofluorescence Findings.
AB  - PURPOSE: This study explored the validity of the First International Consensus on
      Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically
      indistinguishable patients, who have direct immunofluorescence (DIF)-negative
      biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed
      diagnosis, of MMP with ocular involvement leads to the inappropriate use of
      topical therapy, the standard of care for causes of cicatrising conjunctivitis
      other than MMP, rather than systemic immunomodulatory therapy, resulting in
      irreversible clinical deterioration in patients with MMP. DESIGN: Prospective,
      cross-sectional study. PARTICIPANTS: Patients meeting the clinical criteria of
      ocular MMP, including those with positive and negative DIF findings. METHODS: A
      case report form was used to collect the demographic details, the clinical
      history, and the results of a detailed clinical assessment by ophthalmologists,
      otolaryngologists, dermatologists, and oral medicine specialists. All anatomic
      sites potentially affected by MMP were examined apart from the esophagus (and
      larynx in a subset). The DIF results were recorded. MAIN OUTCOME MEASURES:
      Differences between DIF-positive and -negative patients in demography, sites of
      involvement, and disease severity as determined by the degree of conjunctival
      scarring (using Tauber staging), central corneal disease (vascularization,
      scarring, ulceration, and conjunctivalization), history of conjunctival or lid
      surgery, and requirement for systemic immunotherapy at the time of screening.
      RESULTS: A total of 73 patients with ocular MMP were recruited, of whom 20 of 73
      (27.4%) had ocular-only disease. There was no significant demographic or clinical
      difference between patients with positive and negative DIF results. This finding
      included differences in disease severity for which the only significant
      difference was that of more severe central corneal disease in DIF-negative
      patients. Asymptomatic disease at different sites was frequent. CONCLUSIONS:
      These findings do not support the classification of DIF-negative patients,
      meeting the clinical criteria for ocular MMP, as having a different disease. This
      category of patients should be accepted as having DIF-negative MMP, for clinical
      management purposes, with patients having inflamed eyes being treated with
      systemic immunomodulatory therapy. The frequent finding of asymptomatic ocular,
      oral, and nasopharyngeal MMP is clinically significant and implies that these
      sites should be routinely screened in asymptomatic patients.

PMID- 29217150
TI  - Breaking the ice.

PMID- 29217151
TI  - Ontologies of life: From thermodynamics to teleonomics: Comment on "Answering
      Schrodinger's question: A free-energy formulation" by Maxwell James Desormeau
      Ramstead et al.

PMID- 29217152
TI  - Advanced cardiopulmonary resuscitation (CPR) in the Catheterization Laboratory:
      Consensus document of the Working Groups of 1) Cardiopulmonary
      Resuscitation/Acute Cardiac Care and 2) Hemodynamic and Interventional
      Cardiology, Hellenic Cardiological Society.

PMID- 29217153
TI  - Patterns of Transition Experience for Parents Going Home from Hospital with their
      Infant after First Stage Surgery for Complex Congenital Heart Disease.
AB  - PURPOSE: The purpose of this study was to explore parents' experiences of one
      specific timepoint in their infant's journey: the transition from hospital to
      home, following the first stage of their infant's cardiac surgery for complex
      congenital heart disease. DESIGN AND METHODS: A prospective longitudinal mixed
      methods study, underpinned with Middle Range Transition Theory (Meleis, Sawyer,
      Im, Hilfinger Messias, & Schumacher, 2000). Face to face and telephone interviews
      were conducted and self-report forms completed by parents at four-time points:
      before discharge (T0), 2weeks after discharge (T1), 8weeks after discharge (T2)
      and after stage two surgery (T3). Interviews were transcribed verbatim before
      inductive thematic analysis. RESULTS: Parents were recruited over a 15-month
      period from 2013 to 2015. Twelve mothers and 4 fathers took part. The infants had
      functionally univentricular heart (left n=10, right n=1) and a systemic shunt
      dependent lesion, tetralogy of Fallot (n=1). Dynamic constructivist and
      constructionist social processes occurred for all parents, involving physical,
      physiological, psychological and cognitive elements within four 'patterns of
      experience', two of which 'safety and security' and 'love and support' are
      presented in this paper. IMPLICATIONS: Parental support is essential; parents
      need to be engaged in discharge planning process and given the opportunity to
      express their needs to ensure that discharge care is truly patient and family
      centered. CONCLUSIONS: Transition from hospital to home was complex and multi
      faceted, with unanticipated physical and emotional transitions superimposed upon
      those that were expected.

PMID- 29217154
TI  - Production of a chimeric protein and its potential application in sero-diagnosis
      of Mycoplasma hominis infection.
AB  - INTRODUCTION: Mycoplasma hominis is an opportunistic pathogen of the human
      genital tract. Detection of antibodies against this organism in human serum or
      plasma is theoretically unreliable because of high variation in bacterial surface
      antigens. In this study, we applied the bioinformatics tools to design a chimeric
      protein constructed of specific, conserved and predicted immuno-dominant epitopes
      from two different membrane proteins, P120 and P80. MATERIAL AND METHODS: Linear
      B-cell epitopes of P120 and P80 were predicted and evaluated by bioinformatics
      tools and the designed chimeric protein was expressed in Escherichia coli. The
      chimeric protein, Mh128, was further analyzed in terms of immuno-reactivity by
      western blotting and enzyme immuno-sorbent assay (ELISA). RESULTS: We found eight
      specific, conserved and immuno-dominant epitopes within P120 and P80 based on the
      bioinformatic studies. The constructed chimeric protein showed immuno-reaction in
      both western-blotting and ELISA tests. DISCUSSION: Because of extensive variation
      of genomic and antigenic structure, diagnosis of M. hominis infection is
      difficult. Mh128 as a predicted specific and conserved recombinant protein can be
      potentially used for sero-diagnosis of M. hominis infection. We plan to develop
      an immuno-assay based on Mh128 and further evaluate the clinical specificity and
      sensitivity of the method.

PMID- 29217155
TI  - Pleiotropic neuropathological and biochemical alterations associated with Myo5a
      mutation in a rat Model.
AB  - In this study, we analyze the neuropathological and biochemical alterations
      involved in the pathogenesis of a neurodegenerative/movement disorder during
      different developmental stages in juvenile rats with a mutant Myosin5a (Myo5a).
      In mutant rats, a spontaneous autosomal recessive mutation characterized by the
      absence of Myo5a protein expression in the brain is associated with a syndrome of
      locomotor dysfunction, altered coat color, and neuroendocrine abnormalities.
      Myo5a encodes a myosin motor protein required for transport and proper
      distribution of subcellular organelles in somatodendritic processes in neurons.
      Here we report marked hyperphosphorylation of alpha-synuclein and tau, as well as
      region-specific buildup of the autotoxic dopamine metabolite, 3,4-dihydroxyphenyl
      acetaldehyde (DOPAL), related to decreased aldehyde dehydrogenases activity and
      neurodegeneration in mutant rats. Alpha-synuclein accumulation in mitochondria of
      dopaminergic neurons is associated with impaired enzymatic respiratory complex I
      and IV activity. The behavioral and biochemical lesions progress after 15 days
      postnatal, and by 30-40 days the animals must be euthanized because of
      neurological impairment. Based on the obtained results, we propose a pleiotropic
      pathogenesis that links the Myo5a gene mutation to deficient neuronal development
      and progressive neurodegeneration. This potential model of a neurodevelopmental
      disorder with neurodegeneration and motor deficits may provide further insight
      into molecular motors and their associated proteins responsible for altered
      neurogenesis and neuronal disease pathogenesis.

PMID- 29217156
TI  - Air-Q(r) versus LMA FastrachTM for fiberoptic-guided intubation: A randomized
      cross-over manikin trial.
AB  - INTRODUCTION: Airway management is still a major cause of anesthesia-associated
      morbidity and mortality. Supraglottic devices are recommended in difficult airway
      management guidelines. The aim of this study was to compare the performance of
      the Air-Q(r) and the LMA FastrachTM for fiberoptic guided tracheal intubation.
      METHODS: Thirty-three anesthesia trainees participated in this randomized
      crossover study. Time to insert the dedicated airways (insertion of the airway
      into the manikin and delivery of two breaths), time to tracheal intubation
      (fiberoptic-guided tracheal intubation), time to remove the dedicated airway
      (removal of the Air-Q(r)/LMA FastrachTM over the tracheal tube) and the opinion
      of the ease of use of the anesthesia trainees were measured. RESULTS: There was
      100% success rate for tracheal intubation with both devices on the first attempt.
      Time to insert the dedicated device and deliver two breaths was 10+/-3s for the
      Air-Q(r) and 11+/-3s for the LMA FastrachTM, P=.07. Time taken to intubate the
      trachea was shorter with the air-Q(r), 38+/-15 s, than with the LMA FastrachTM,
      47+/-19s, P=.017. Overall procedure time was significantly shorter with the Air
      Q(r) as compared with the LMA FastrachTM, with a mean time of 74+/-21s and 87+/
      28s respectively, P=.002. Air-Q(r) removal was considered easier than LMA
      FastrachTM removal, P=.005. There were no tube dislodgements during the removal
      of the dedicated airways. CONCLUSIONS: Inexperienced anesthesia residents can
      perform fiberoptic-guided intubation through Air-Q(r) and LMA FastrachTM in a
      clinically acceptable time with high success.

PMID- 29217157
TI  - Functional histamine H3 and adenosine A2A receptor heteromers in recombinant
      cells and rat striatum.
AB  - In the striatum, histamine H3 receptors (H3Rs) are co-expressed with adenosine
      A2A receptors (A2ARs) in the cortico-striatal glutamatergic afferents and the
      GABAergic medium-sized spiny neurons that originate the indirect pathway of the
      basal ganglia. This location allows H3Rs and A2ARs to regulate the striatal
      GABAergic and glutamatergic transmission. However, whether these receptors can
      physically interact has not yet been assessed. To test this hypothesis, a
      heteromer-selective in vitro assay was used to detect functional complementation
      between a chimeric A2AR302-Galphaqi4 and wild-type H3Rs in transfected HEK-293T
      cells. H3R activation with the agonist RAMH resulted in Ca2+ mobilization (pEC50
      7.31 +/- 0.23; maximal stimulation, Emax 449 +/- 25% of basal) indicative of
      receptor heterodimerization. Functional H3R-A2AR heteromers were confirmed by co
      immunoprecipitation and observations of differential cAMP signaling when both
      receptors were co-expressed in the same cells. In membranes from rat striatal
      synaptosomes, H3R activation decreased A2AR affinity for the agonist CGS-21680
      (pKi values 8.10 +/- 0.04 and 7.70 +/- 0.04). Moreover, H3Rs and A2ARs co
      immunoprecipitated in protein extracts from striatal synaptosomes. These results
      support the existence of a H3R-A2AR heteromer with possible physiological
      implications for the modulation of the intra-striatal transmission.

PMID- 29217158
TI  - Evidence based traditional anti-diarrheal medicinal plants and their
      phytocompounds.
AB  - Traditional medicines are an integral component of alternative health care
      systems used by millions of the people worldwide. Traditionally used herbals are
      multi-constituent medications, safety and efficacy of which is based on
      experiences of the practitioners, whereas modern drugs are single molecules,
      rigorously tested, structurally optimized and toxicologically cleared. Plants are
      being recognized as potential source of drug discovery and more than 80% of
      modern drugs are derived directly from natural sources (plants, microbes, cells
      etc.) or their molecules/compounds. A large number of traditional medicinal
      plants are used for the treatment of diarrhea and related gastrointestinal
      disorders. Many of these plants have been scientifically validated in animal
      models of diarrhea. However, very few of these have been clinically tested
      through controlled trials. The article highlights various traditional anti
      diarrheal medicinal plants, which are shown to have high efficacy in in-vivo
      models. It was noticed that few active phytomolecules have been also identified
      from these plants however these have not been substantially explored in terms of
      their clinical efficacy and safety. This review also describes the potential
      herbal extracts which may be investigated for identification of novel active
      molecules against diarrhea and other gastrointestinal disorders. Robust clinical
      trials of lead plants/phyto-molecules will be needed to develop novel, effective
      and safe phyto-medicines for combating diarrhea and associated disorders.

PMID- 29217159
TI  - The chemical composition and trypanocidal activity of volatile oils from
      Brazilian Caatinga plants.
AB  - Essential/volatile oils (EOs) from plants used in the traditional medicine are
      known as a rich source of chemically diverse compounds with relevant biological
      activities. In this work we analysed the chemical composition and the in vitro
      effects of EOs from leaves of Eugenia brejoensis (EBEO), Hyptis pectinata (HPEO),
      Hypenia salzmannii (HSEO), Lippia macrophylla (LMEO) and seeds of Syagrus
      coronata (SCEO) on Trypanosoma cruzi, the etiological agent of Chagas disease.
      The EOs were extracted through hydrodistillation and its chemical composition
      analysed by GC/MS. The trypanocidal activity against epi- and trypomastigotes was
      evaluated by optical microscopy and the cytotoxicity to mammalian cells by MTT.
      The effects of EOs on parasite infection in macrophages were estimated by
      determining the survival index and the percentage of infection inhibition. The
      cytotoxicity against mammalian cells was compared to those of parasite by
      determining the Selectivity Index (SI). Overall, 114 compounds were identified:
      The main constituents of EOS were: delta-cadinene (15.88%), trans-caryophyllene
      (9.77%) e alpha-Muurolol (9.42%) for EBEO; trans-caryophyllene (15.24%),
      bicyclogermacrene (7.33%) e cis-calamenene (7.15%) for HFEO; trans-caryophyllene
      (30.91%), caryophyllene oxide (13.19%) and spathulenol (5.68%) for HPEO;
      Xanthoxylin (17.20%) trans-caryophyllene (14.34%) and methyl-eugenol (5.60%) for
      HSEO; Thymol (49.81%), carvacrol (31.6%) and sigma-cimene (10.27%) for LMEO and
      octanoic acid (38.83%) dodecanoic acid (38.45%) and decanoic acid (20.51%) for
      SCEO. All the tested oils showed an inhibitory effect on the growth and survival
      of all forms of T. cruzi and moderate cytotoxicity towards the mammalian cells
      (100 < CC50 < 500 MUg/mL). The EO of E. brejoensis was the most effective against
      the parasite presenting higher Selectivity Index for trypo- (SI = 14.45) and
      amastigote forms (SI = 20.11). Except for SCEO, which was the most cytotoxic for
      both parasite and mammalian cells, all the oils demonstrated to be more selective
      for the parasite than the reference drug benznidazole. Taken together our results
      point the essential oils from Caatinga plants, especially Eugenia brejoensis, as
      promissory agents for the development of new drugs against Chagas disease.

PMID- 29217160
TI  - Interaction between Gallic acid and Asparaginase to potentiate anti-proliferative
      effect on lymphoblastic leukemia cell line.
AB  - BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) fails in some cases
      and the side effects cause mortality in certain patients. Gallic acid (GA), a
      polyhydroxyphenolic compound has biological functions including anti
      proliferative properties. The aim of the present study was to investigate the
      growth inhibition effects of GA in combination with asparaginase (ASP), as a
      component of combination chemotherapy, in a lymphoblastic leukemia cell line.
      METHODS: Jurkat cells were incubated with different concentrations of GA with or
      without ASP. Proliferation inhibition was investigated using MTS test. The level
      of apoptosis alterations were evaluated using flow cytometry. The expression of
      Fas gene level and surface expression were investigated by quantitative real time
      PCR and flow cytometry respectively. RESULTS: GA at 50MUM concentration and ASP
      at 0.5 IU/ml inhibited 50% cell proliferation in 48 hours. GA also increased the
      inhibitory effect of ASP and some combinations had synergistic results. The
      increase of cell apoptosis and Fas expression were observed in GA-treated cells
      compared to control. GA increased the effect of ASP on proliferation inhibition,
      induction of apoptosis and Fas expression. CONCLUSION: GA is an effective
      component in proliferation inhibition, apoptosis induction and enhancement of Fas
      expression level in Jurkat cell line. GA in some combination with ASP increases
      the effect of the latter on the cells. The study of the mechanism of these
      effects could be a further step towards target therapy. This study is a
      preliminary phase to the use of GA and should be carried out by more
      comprehensive study and animal models.

PMID- 29217161
TI  - MiR-1202 suppresses hepatocellular carcinoma cells migration and invasion by
      targeting cyclin dependent kinase 14.
AB  - Currently, hepatocellular carcinoma (HCC) patients still have poor survival
      outcomes mainly due to the powerful mobility of HCC cells. Increasing evidences
      hint that abnormally expressed miRNAs are capable to modulate HCC cells invasion
      and migration. MiR-1202 has been proposed as a ponderable molecular tumor marker
      in a variety of tumors. Here, results from real-time PCR indicated the decreased
      expression of miR-1202 in HCC. Clinically, statistical analysis showed that miR
      1202 under-expression was closely associated with metastasis-related
      clinicopathologic characteristics. In addition, 5-year overall survival (OS) and
      disease-free survival (DFS) rates of HCC patients with high miR-1202 expression
      were much better than that in low miR-1202 group. Functionally, gain- and loss-of
      -function studies were performed to investigate the roles of miR-1202.
      Intriguingly, Would healing assay and Transwell assays indicated that elevated
      miR-1202 weakened HCC cells migration and invasion abilities, while miR-1202
      knockdown presented the contrary effects. Furthermore, cyclin dependent kinase 14
      (CDK14) was identified as a downstream target of miR-1202 by bioinformatics
      analysis, Dual luciferase reporter assay, detection of CDK14 expression and
      Pearson correlation analysis. More importantly, rescue experiments demonstrated
      that CDK14 mediated miR-1202 to exert its anti-tumor effects, which further
      confirmed the above finding. Taken together, miR-1202 may act as a new biomarker
      and potential therapeutic target for HCC.

PMID- 29217162
TI  - Association of inflammatory mediators with pain perception.
AB  - Treatment of pain has always been a major goal in the clinic, as it is related to
      several pathological conditions of inflammatory origin and surgical procedures,
      which are associated with inflammatory mediators. Understanding the molecular
      mechanisms underlying the association between inflammatory mediators and pain
      perception, from peripheral to central sensitization, can provide the basis for
      the development of new pharmacological treatments. Despite safety concerns, till
      date, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to
      be efficacious, safe, and well tolerated by patients. Thus, choosing the
      appropriate administration route, developing new formulations and lowering the
      efficacious dose represent, currently, effective means of treating inflammation
      and relieving the pain, without inducing significant side effects.

PMID- 29217163
TI  - CX3CR1 regulates osteoarthrosis chondrocyte proliferation and apoptosis via
      Wnt/beta-catenin signaling.
AB  - OBJECTIVE: The study was aimed to investigate the impact of CX3CR1 expression on
      the proliferation and apoptosis of osteoarthrosis (OA) chondrocytes through Wnt/
      beta-catenin pathway. METHODS: The expression levels of CX3CR1 and Wnt/beta
      catenin pathway-related genes mRNA and protein in OA chondrocytes were examined
      by qRT-PCR and western blot. MTT and flow cytometry (FCM) assays were employed to
      assess cell proliferation, cell cycle and apoptosis. XAV-939, a Wnt/beta-catenin
      pathway inhibitor, was used to inhibit the pathway. RESULTS: CX3CR1 was
      significantly overexpressed in OA cartilages than that in normal articular
      cartilages (P < 0.05). After siCX3CR1 transfection, the expression level of Wnt
      3, nuclear beta-catenin, Cyclin D1, MMP-13 and phosphorylated GSK-3beta
      significantly increased, while cytoplasm beta-catenin, GSK-3beta and
      phosphorylated beta-catenin expression was inhibited (P<0.05). XAV-939abolished
      the effects of siCX3CR1 on proliferation, apoptosis and cell cycle progression of
      OA chondrocytes (P<0.05). CONCLUSIONS: CX3CR1 regulated chondrocyte proliferation
      and apoptosis through Wnt/beta-catenin signaling pathway. The overexpression of
      CX3CR1 in chondrocytes of OA may be closely related to the pathogenesis and
      progression of OA.

PMID- 29217164
TI  - The protective role of crocin in tartrazine induced nephrotoxicity in Wistar
      rats.
AB  - The present study was conducted to investigate the changes in rat kidney tissues
      after administration of tartrazine (T) and crocine (Cr). The latter was applied
      for its protective properties. The present study was conducted with the approval
      of Inonu University, Faculty of Medicine, Experimental Animals Ethics Committee.
      Forty rats were randomly divided into 4 equal groups (Control, T, Cr, T + Cr). At
      the end of the experiment, the rats were decapitated. Biochemical and
      histopathological studies were conducted on excised rat kidney tissues. It was
      determined that there was a significant increase in MDA, TOS, SOD, CAT, Bun,
      Creatinine levels in tartrazine administered rat kidney tissues for 21 days,
      while GSH and TAS levels decreased (P <= 0.05) when compared to all other groups.
      On the other hand, it was identified that Cr administration statistically
      significantly increased GSH and TAS levels in rat kidney tissues when compared to
      all other groups and decreased MDA and TOS levels to control group levels (P <
      0.05). T group kidney sections exhibited different degrees of collapse in the
      glomeruli. In most sections, different levels of inflammatory cell infiltration
      and vascular and capillary congestion were detected in peritubular interstitial
      tissue. It was determined that T leads to adverse effects on rat kidney tissues.
      Administration of Cr + T prevented T induced nephrotoxicity. Thus, it was
      concluded that Cr could be utilized as a new type of anti-tartrazine toxicity
      agent.

PMID- 29217165
TI  - Anxiolytic- and antidepressant-like activities of a methanolic extract of Morinda
      citrifolia Linn. (noni) fruit in mice: Involvement of benzodiazepine-GABAAergic,
      serotonergic and adrenergic systems.
AB  - This study presents anxiolytic- and antidepressant-like effects of a methanolic
      extract of Morinda citrifolia Linn. (noni) fruit (MMC) in well-established mouse
      models of anxiety and depression. The administration of MMC (1 g/kg, p.o.) and
      diazepam (1 mg/kg, i.p.) significantly attenuated anxiety-like behaviour in mice
      by increasing the percentage of time spent and number of entries in the open arms
      in the elevated plus maze (EPM), and significantly enhanced the exploration in
      the light box in the light/dark test (LDT). The pre-treatment with flumazenil (6
      mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) or WAY 100635 (1 mg/kg, i.p.)
      antagonized the anxiolytic-like effect elicited by MMC (1 g/kg, p.o.). These
      results suggest the possible involvement of benzodiazepine-GABAAergic and
      serotonergic mechanisms in the anxiolytic-like effect of noni fruit. Meanwhile,
      in the antidepressant study, the administration of MMC (0.5 and 0.75 g/kg, p.o.)
      and desipramine (30 mg/kg, i.p.) significantly reduced the duration of immobility
      in the tail suspension test (TST). Furthermore, pre-treatment of mice with 4
      chloro-DL-phenylalanine methyl ester hydrochloride (PCPA; 100 mg/kg, i.p., an
      inhibitor of serotonin synthesis) for four consecutive days or a single dose of
      WAY 100635 (1 mg/kg, i.p., 5HT1A receptor antagonist) or alpha-methyl-DL-tyrosine
      (AMPT; 100 mg/kg, i.p., an inhibitor of noradrenaline synthesis) significantly
      reversed the anti-immobility effect of MMC (0.5 g/kg, p.o.) in TST by indicating
      the specific involvement of the serotonergic and noradrenergic systems in the
      antidepressant-like effect of noni fruit. Taken together, these findings suggest
      that MMC has both anxiolytic- and antidepressant-like activities to be resorted
      as a valuable alternative therapy for comorbid anxiety and depressive conditions.

PMID- 29217166
TI  - Long non-coding RNA SOX21-AS1 sponges miR-145 to promote the tumorigenesis of
      colorectal cancer by targeting MYO6.
AB  - Emerging evidences have proved that long non-coding RNAs (lncRNAs) act as
      important molecular regulator in the tumor progression, including colorectal
      cancer (CRC). LncRNA SOX21-AS1 has been verified as oncogenic molecular in other
      cancers and tumorigenesis. In present study, our team investigates the clinical
      characteristic and molecular function in CRC carcinogenesis. Results showed that
      lncRNA SOX21-AS1 expression was significantly over-expressed in CRC tissue
      samples and cells. The aberrant over-expression of SOX21-AS1 indicated poor
      prognosis of CRC patients. In vitro and in vivo validation experiments, SOX21-AS1
      silencing inhibited the proliferation, invasion, and decreased the tumor growth
      of CRC cells. Moreover, miR-145 was proved to be the target of SOX21-AS1,
      besides, myosin VI (MYO6) was found to be one of the targets of miR-145 using
      bioinformatics prediction programs and rescue confirmation experiments. In
      summary, our study reveals the tumorigenic effect of lncRNA SOX21-AS1 in CRC
      cells via targeting miR-145/MYO6, providing a novel insight for CRC
      carcinogenesis.

PMID- 29217167
TI  - Potential protective effect of Pistacia lentiscus oil against chlorpyrifos
      induced hormonal changes and oxidative damage in ovaries and thyroid of female
      rats.
AB  - The purpose of this study was to evaluate the protective effect of Pistacia
      lentiscus oil (PLO), known for its antioxidant properties, on chlorpyrifos (CPF)
      induced alterations in the thyroid, reproductive hormone levels, and oxidative
      damage in the ovaries and thyroid of adult Wistar rats. The animals were treated
      with orally administered PLO (2 mL/kg), CPF (6.75 mg/kg), and a combination of
      CPF and PLO for 30 days. Serum levels of luteinizing hormone (LH), follicle
      stimulating hormone (FSH), progesterone (Pg), estradiol (E2), triiodothyronine
      (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were assessed using
      chemiluminescence assay. Malondialdehyde (MDA), protein carbonyl (PC), and
      reduced glutathione (GSH) levels were examined in the ovaries and thyroid glands.
      The oil principal volatile compounds detected by gas chromatography analysis
      were: myrcene, alpha-pinene and limonene (26.21, 22.66 and 10.33%, respectively).
      No significant differences were observed between serum concentrations of TSH and
      FSH in the examined experimental groups. However, serum concentrations of LH, E2,
      Pg, T3, and T4 decreased significantly in CPF-treated rats in comparison with the
      controls. The body weight and relative weight of ovaries and thyroids in this
      group were also significantly reduced. The MDA and PC content increased
      significantly, while the GSH content was markedly depressed in the thyroid and
      ovaries of rats treated with CPF. Co-administration of PLO and CPF effectively
      ameliorated the adverse effects; the oxidative damage was reduced and the levels
      of thyroid and reproductive hormones restored to a normal range. In conclusion,
      it appears that PLO substantially alleviates the CPF-induced oxidative damage and
      hormonal alterations.

PMID- 29217168
TI  - The stories of women who are transferred due to threat of preterm birth.
AB  - BACKGROUND: Women at risk of preterm birth before 32 weeks gestation are
      routinely transferred to facilitate birth at a hospital that has Neonatal
      Intensive Care. The clinical outcomes of being 'in-born" improves newborn and
      neonatal outcomes is well documented. However little is known about the women's
      experiences when such a complication occurs. METHOD: Using the NSW Agency for
      Clinical Innovation Patient and Carer stories method, 10 women were purposively
      invited and consented to tell their stories. Semi-structured interviews were
      undertaken during their inpatient stay and then again, by telephone in the months
      following their baby's due date. Themes were identified, illustrated by
      exemplars. RESULTS: All women were multiparous. Without exception, the women said
      that having the support of their family was the most important factor in coping
      with their unexpected hospitalisation and the anxiety of having to deal with the
      uncertainty of their pregnancy outcome. The most difficult aspect of their
      experience was the distress of being separated from their children and families
      and undue stress and distress from their partners. Other issues they identified
      were: physical difficulties during transfer; information overload as they sought
      to understand their changing circumstances; accommodation issues; and financial
      stress resulting from their relocation. CONCLUSIONS: All women perceived their
      midwifery, obstetric and neonatal care to be exceptional and their neonatal
      outcomes were positive. Improvements may be made by facilitating family contact
      allowing flexible visiting, assisting with partner/family accommodation,
      providing women with their basic needs during transport and providing assistance
      to relieve financial strain.

PMID- 29217169
TI  - Enabling new graduate midwives to work in midwifery continuity of care models: A
      conceptual model for implementation.
AB  - BACKGROUND: High-level evidence demonstrates midwifery continuity of care is
      beneficial for women and babies. Women have limited access to midwifery
      continuity of care models in Australia. One of the factors limiting women's
      access is recruiting enough midwives to work in continuity. Our research found
      that newly graduated midwives felt well prepared to work in midwifery led
      continuity of care models, were well supported to work in the models and the main
      driver to employing them was a need to staff the models. However limited
      opportunities exist for new graduate midwives to work in midwifery continuity of
      care. AIM: The aim of this paper therefore is to describe a conceptual model
      developed to enable new graduate midwives to work in midwifery continuity of care
      models. METHOD: The findings from a qualitative study were synthesised with the
      existing literature to develop a conceptual model that enables new graduate
      midwives to work in midwifery continuity of care. FINDINGS: The model contains
      the essential elements to enable new graduate midwives to work in midwifery
      continuity of care models. DISCUSSION: Each of the essential elements discussed
      are to assist midwifery managers, educators and new graduates to facilitate the
      organisational changes required to accommodate new graduates. CONCLUSION: The
      conceptual model is useful to show maternity services how to enable new graduate
      midwives to work in midwifery continuity of care models.

PMID- 29217170
TI  - Update: Topical Anesthetics for Pain Control During Repair of Dermal Laceration.

PMID- 29217171
TI  - What Is the Utility of Coronary Computed Tomography Angiography Compared With
      Standard of Care for the Evaluation of Acute Chest Pain?

PMID- 29217172
TI  - Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1
      adipocytes.
AB  - Browning of white adipocytes (beiging) is an attractive therapeutic strategy
      against obesity and its associated metabolic complications. Nobiletin (NOB) is a
      polymethoxylated flavone present in citrus fruits and has been reported to have
      anti-obesity effects. Here, we report that nobiletin exerts dual modulatory
      effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and
      amelioration of stress in adipocytes. Nobiletin-induced beiging was investigated
      by determining expression levels of beige-specific genes and proteins by RT-PCR
      and immunoblot analysis, respectively. Nobiletin treatment rapidly elevated the
      expression levels of beige-specific genes such as Cd137, Cidea, Tbx1, and Tmem26.
      Further, nobiletin enhanced expression of the key transcription factors
      C/EBPbeta, PPARdelta, and PPARalpha, which are responsible for remodeling of
      white adipocytes. Nobiletin also strikingly activated HIB1B brown adipocytes and
      induced mitochondrial biogenesis in 3T3-L1 white adipocytes. In addition,
      nobiletin altered the expression of several lipid metabolism-related proteins
      such as ACOX1, CPT1, FAS, p-PLIN, SREBP and SIRT1. Moreover, nobiletin
      ameliorated stress in adipocytes by inhibiting expression levels of key stress
      molecules such as JNK and c-JUN. Nobiletin-induced browning could be mediated by
      tight regulation of kinases, as nobiletin induced PKA and p-AMPK at the protein
      expression level, and inhibition of PKA and p-AMPK by H-89 and dorsomorphin,
      respectively, abolished expression of the thermogenic markers PGC-1alpha and
      UCP1. Taken together, our findings suggest that nobiletin plays a modulatory role
      in adipocytes via induction of browning in 3T3-L1 white adipocytes and activation
      of HIB1B brown adipocytes combined with amelioration of stress in adipocytes,
      thereby exhibiting therapeutic potential against obesity.

PMID- 29217173
TI  - 7-Fluoro-1,3-diphenylisoquinoline reverses motor and non-motor symptoms induced
      by MPTP in mice: Role of striatal neuroinflammation.
AB  - Parkinson's disease (PD) is a dopaminergic neurodegenerative disorder, which
      presents motor and non-motor symptoms. 7-Fluoro-1,3-diphenylisoquinoline (FDPI)
      is an isoquinoline compound with antioxidant and antidepressant properties. This
      study investigated whether FDPI reverses motor and non-motor symptoms in an acute
      mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      It was also assessed the anti-inflammatory mechanisms in FDPI pharmacological
      action. C57Bl/6 male adult mice received four MPTP (20mg/kg, intraperitoneal) or
      saline (vehicle) injections to induce an acute PD model. FDPI (10mg/kg,
      intragastric) was daily administered to mice from the 2nd to 9th day after the
      induction and mice performed the behavioral tests on the 8th and 9th days.
      Striatum samples were collected for biochemical and molecular analyses. The
      results of the rotarod and challenging beam tests demonstrated that the
      administration of FDPI attenuated the impairments in balance and coordination of
      mice induced by MPTP. The FDPI reversed the short-term memory deficit and
      depressive-like behavior induced by MPTP in mice. FDPI attenuated the reduction
      in the striatal tyrosine hydroxylase levels, and it reversed the increase in the
      cyclooxygenase-2 levels and myeloperoxidase activity caused by MPTP in mice.
      Therefore, FDPI reversed motor and non-motor symptoms induced by an acute PD
      model and its restorative effects seem to be mediated by an anti-inflammatory
      action associated with a modulation of the striatal cyclooxygenase-2 levels and
      myeloperoxidase activity.

PMID- 29217175
TI  - Reactivity of IgM antibodies elicited by PEGylated liposomes or PEGylated
      lipoplexes against auto and foreign antigens.
AB  - Polyethylene glycol (PEG) is an attractive tool for the development of
      nanoparticle-based cancer therapy since it endows nanoparticles with extended
      circulation properties. Nevertheless, recent reports have revealed that
      intravenous injection of either PEGylated liposomes (SLs) or PEGylated lipoplex
      (PLpx) could elicit an anti-PEG immunoglobulin (IgM) response in a T cell
      independent (TI) manner that would substantially compromise the in vivo fate of
      PEGylated products upon repeated administration. In the same context, viral or
      bacterial infections trigger the production of polyreactive IgM that binds both
      self and foreign antigens. The polyreactivity of IgM elicited by SLs or PLpx, to
      bacteria and other polymers, however, is yet to be elucidated. In this study, the
      polyreactivity of IgM elicited by SLs or PLpx was challenged against different
      bacteria (TI antigens) and against synthetic polymer composed of repetitive
      structures (PVP-360 or FITC-dextran). Results demonstrated that anti-PEG IgM
      elicited by either SLs or PLpx showed no reactivity to various bacteria examined,
      while the IgM showed remarkable reactivity to both PVP-360 and FITC-dextran. In
      addition, interestingly, anti-PEG IgM elicited by either SLs or PLpx showed no
      antinuclear antibody-like immune reactivity, and, therefore, treatment with
      either SLs or PLpx was not expected to exacerbate autoimmune diseases such as
      systemic lupus erythematosus. Collectively, our findings could provide
      information supporting the safety of PEGylated nanoparticle-based pharmaceutics,
      particularly in patients with autoimmune diseases.

PMID- 29217174
TI  - N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel alpha-hydroxyamide with
      anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage
      gated sodium channels.
AB  - In patients with epilepsy, anxiety and depression are the most frequent
      psychiatric comorbidities but they often remain unrecognized and untreated. We
      report herein the antidepressant-like activity in two animal models, tail
      suspension and forced swimming tests, of six anticonvulsants alpha-hydroxyamides.
      From these, N-propyl-2,2-diphenyl-2-hydroxyacetamide (compound 5) emerged not
      only as the most active as anticonvulsant (ED50 = 2.5mg/kg, MES test), but it
      showed the most remarkable antidepressant-like effect in the tail suspension and
      forced swimming tests (0.3-30mg/kg, i.p.); and, also, anxiolytic-like action in
      the plus maze test (3-10mg/kg, i.p.) in mice. Studies of its mechanism of action,
      by means of its capacity to act via the GABAA receptor ([3H]-flunitrazepam
      binding assay); the 5-HT1A receptor ([3H]-8-OH-DPAT binding assay) and the
      voltage-gated sodium channels (either using the patch clamp technique in hNav 1.2
      expressed in HEK293 cell line or using veratrine, in vivo) were attempted. The
      results demonstrated that its effects are not likely related to 5-HT1A or
      GABAAergic receptors and that its anticonvulsant and antidepressant-like effect
      could be due to its voltage-gated sodium channel blocking properties.

PMID- 29217176
TI  - A strong adjuvant based on glycol-chitosan-coated lipid-polymer hybrid
      nanoparticles potentiates mucosal immune responses against the recombinant
      Chlamydia trachomatis fusion antigen CTH522.
AB  - Induction of mucosal immunity with vaccines is attractive for the immunological
      protection against pathogen entry directly at the site of infection. An example
      is infection with Chlamydia trachomatis (Ct), which is the most common sexually
      transmitted infection in the world, and there is an unmet medical need for an
      effective vaccine. A vaccine against Ct should elicit protective humoral and cell
      mediated immune (CMI) responses in the genital tract mucosa. We previously
      designed an antibody- and CMI-inducing adjuvant based on poly(dl-lactic-co
      glycolic acid) (PLGA) nanoparticles modified with the cationic surfactant
      dimethyldioctadecylammonium bromide and the immunopotentiator trehalose-6,6'
      dibehenate. Here we show that immunization with these lipid-polymer hybrid
      nanoparticles (LPNs) coated with the mucoadhesive polymer chitosan enhances
      mucosal immune responses. Glycol chitosan (GC)-modified LPNs were engineered
      using an oil-in-water single emulsion solvent evaporation method. The
      nanoparticle design was optimized in a highly systematic way by using a quality
      by-design approach to define the optimal operating space and to gain maximal
      mechanistic information about the GC coating of the LPNs. Cryo-transmission
      electron microscopy revealed a PLGA core coated with one or several concentric
      lipid bilayers. The GC coating of the surface was identified as a saturable, GC
      concentration-dependent increase in particle size and a reduction of the zeta
      potential, and the coating layer could be compressed upon addition of salt.
      Increased antigen-specific mucosal immune responses were induced in the lungs and
      the genital tract with the optimized GC-coated LPN adjuvant upon nasal
      immunization of mice with the recombinant Ct fusion antigen CTH522. The mucosal
      responses were characterized by CTH522-specific IgG/IgA antibodies, together with
      CTH522-specific interferon gamma-producing Th1 cells. This study demonstrates
      that mucosal administration of CTH522 adjuvanted with chitosan-coated LPNs
      represents a promising strategy to modulate the magnitude of mucosal vaccine
      responses.

PMID- 29217177
TI  - C-reactive protein value is a strong predictor of acute appendicitis in young
      children.

PMID- 29217178
TI  - Factors associated with advanced cardiac care in prehospital chest pain patients.
AB  - INTRODUCTION: Many patients transported by emergency medical services (EMS) may
      require advanced cardiac care but do not have ST-segment elevation (STEMI) on the
      initial prehospital EKG. We sought to identify factors associated with the need
      for advanced cardiac care in undifferentiated EMS patients reporting chest pain
      in the absence of STEMI on EKG. METHODS: We performed a retrospective analysis of
      all adult patients, reporting atraumatic chest pain from a single EMS agency,
      presenting to a single, urban hospital over a 10-year period. Patients with STEMI
      on prehospital electrocardiogram were excluded. Patient demographics, chest pain
      characteristics and prehospital factors were abstracted for all patients. We
      identified those patients that required advanced cardiac care and performed
      regression analysis to determine associated factors. RESULTS: A total of 956
      charts were analyzed. Of this total, 193 patients (20.2%) met the primary
      composite outcome. Of the outcome group, 185 patients (95.9%) had coronary artery
      disease documented on cardiac catheterization, 22 patients (11.4%) underwent
      CABG, and seven patients (3.6%) died in the hospital. Most significant variables
      (multivariable IRR) included age (1.02), male gender (1.65), history of MI
      (1.47), PCI (1.66), hyperlipidemia (1.40), diaphoresis (1.51), home aspirin
      (1.53), and improvement with EMS treatment (1.60). CONCLUSION: We have identified
      several factors that could be considered when risk stratifying prehospital
      patients reporting chest pain. While potentially predictive, the factors are
      broad and support the need for other objective factors that could augment
      prediction of patients who may benefit from early advanced cardiac care.

PMID- 29217179
TI  - More questions than answers - ALS interventions for out of hospital cardiac
      arrest.

PMID- 29217180
TI  - Structure based mimicking of Phthalic acid esters (PAEs) and inhibition of
      hACMSD, an important enzyme of the tryptophan kynurenine metabolism pathway.
AB  - Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      (hACMSD) is a zinc containing amidohydrolase which is a vital enzyme of the
      kynurenine pathway in tryptophan metabolism. It prevents the accumulation of
      quinolinic acid (QA) and helps in the maintenance of basal Trp-niacin ratio. To
      assess the structure based inhibitory action of PAEs such as DMP, DEP, DBP, DIBP,
      DEHP and their metabolites, these were docked into the active site cavity of
      hACMSD. Docking results show that the binding affinities of PAEs lie in the
      comparable range (-4.9 kca/mol-7.48kcal/mol) with Dipicolinic acid (
      6.21kcal/mol), a substrate analogue of hACMSD. PAEs interact with the key
      residues such as Arg47 and Trp191 and lie within the 4A vicinity of zinc metal at
      the active site of hACMSD. Dynamics and stability of the PAEs-hACMSD complexes
      were determined by performing molecular dynamics simulations using GROMACS 5.14.
      Binding free energy calculations of the PAEs-hACMSD complexes were estimated by
      using MMPBSA method. The results emphasize that PAEs can structurally mimic the
      binding pattern of tryptophan metabolites to hACMSD, which further leads to
      inhibition of its activity and accumulation of the quinolate in the kynurenine
      pathway of tryptophan metabolism.

PMID- 29217181
TI  - Enhancement of intrinsic fluorescence of human carbonic anhydrase II upon
      topiramate binding: Some evidence for drug-induced molecular contraction of the
      protein.
AB  - In this report, the effect of topiramate (TPM), an anticonvulsant sulfamate drug,
      on the structure of human carbonic anhydrase II (hCA II) was investigated by
      spectroscopic techniques. The intrinsic fluorescence experiments indicated that
      TPM binding causes enhancement of enzyme fluorescence via decreasing the internal
      quenching and energy transfer efficiency, the result supported by molecular
      dynamics simulation. Thermodynamic analysis of the binding process suggested that
      hydrogen bonding and van der Waals interactions are the major forces in the
      interaction of TPM with hCA II. The far-UV circular dichroism (CD) results showed
      that TPM caused increment in alpha-helical and beta-sheet content of hCA II
      whereas, near-UV CD experiments in the presence of the drug showed induction of
      some compactness in the enzyme tertiary structure. The number of accessible
      tryptophans and protein surface hydrophobicity index of the enzyme were reduced
      in the presence of TPM which confirms the enzyme structural compactness upon drug
      binding. In addition, the enzyme thermal stability was increased in the presence
      of the drug. It seems that the induction of compactness in the enzyme structure
      upon drug binding may be responsible for increment of its conformational
      stability.

PMID- 29217182
TI  - Mass spectrometry characterization for N-glycosylation of immunoglobulin Y from
      hen egg yolk.
AB  - Immunoglobulin Y (IgY) is a new therapeutic antibody that exists in hen egg yolk.
      It is a glycoprotein, not much is known about its N-glycan structures, site
      occupancy and site-specific N-glycosylation. In this study, purified protein from
      hen egg yolk was identified as IgY based on SDS-PAGE and MALDI-TOF/TOF MS. N
      glycan was released from IgY using peptide-N4-(N-acetyl-beta-glucosaminyl)
      asparagine-amidase treatment, and the molecular weight of IgY was calculated
      using the difference between the molecular weight of IgY and deglycosylated IgY.
      Two potential N-Glycosylation sites (ASN308 and ASN409) were detected on IgY by
      nanoLC-ESI MS. Sugar chains were separated using normal phase liquid
      chromatography after fluorescence labeling, and 17 N-glycan structures were
      confirmed using ESI-MS. The sugar chain pattern contained high-mannose
      oligosaccharide, hybrid oligosaccharide and complex oligosaccharide. These
      results could lead to other important information regarding IgY glycosylation.

PMID- 29217183
TI  - The structural features of the sulfated heteropolysaccharide (ST-1) from
      Sargassum thunbergii and its neuroprotective activities.
AB  - Polysaccharide (ST) was prepared from Sargassum thunbergii using hot water. Two
      fractions (ST-1 and ST-2) were prepared using anion exchange chromatography. One
      desulfated polysaccharide (ST-1-DS) was also prepared. Electrospray ionization
      mass spectrometry (ESI-MS) performed on ST-1-DS showed that the desulfated
      polysaccharides contained methyl glycosides of mono-sulfated and di-sulfated
      galacto-fucooligosaccharides. This result suggested that ST-1 might contain
      sulfated galactofucan, which consists of a backbone of alternating (Gal)n and
      (Fuc)n and sulfated randomly on Gal and mainly on C-2 in Fuc. In addition, ST-1
      was degraded in 1M sulfuric acid. The solution was centrifuged, and the
      supernatant was concentrated and precipitated in ethanol to obtain the
      precipitate (ST-1-P). ST-1-P was then separated using gel chromatography and
      anion exchange chromatography to obtain the oligomers. ESI-MS spectra of
      oligomers indicated that ST-1 mostly contained sulfated glucuronomannan and
      fucoglucuronan. ESI-MS with collision-induced dissociation tandem mass
      spectrometry (ESI-CID-MS/MS) suggested that glucuronomannan contained alternating
      2-linked Man and 4-linked GlcA, while fucoglucuronan contained 4-linked
      glucuronan with branched Fuc at C-3. Finally, the neuroprotective activities of
      ST, ST-1, ST-2 and MIX (a mixture of ST-1 and ST-2) were determined. ST showed
      the most neuroprotective activity, which indicated that ST might be a good
      candidate for curing neurodegenerative diseases.

PMID- 29217184
TI  - Formulation of novel chitosan guargum based hydrogels for sustained drug release
      of paracetamol.
AB  - The report presents the formulation of hydrogel based on biopolymers chitosan and
      guar gum after cross-linking for sustained release of a commonly used orally
      prescribed analgesic Paracetamol. The oral ingestion of Paracetamol is associated
      with complications of the gastric tract and liver metabolism that can be
      effectually avoided by using transdermal drug delivery systems. The formulated
      transdermal patch was characterized for physicochemical properties including
      swelling, bonding pattern (using FTIR Fourier Transform Infra-Red and Scanning
      Electron Microscopy SEM) and antimicrobial activity. Biocompatibility and
      cytotoxicity was examined in vitro using cell culture in HeLa cell lines. After
      characterizing the novel formulated hydrogel were employed for the preparation of
      drug encapsulated in alginate beads as a transdermal patch. After formulation of
      the transdermal patch, the drug release was studied using an avian skin model.
      The results followed zero order kinetics and Non-Fickian law for diffusion.
      Paracetamol due to its small molecular mass (151.163g/mol) released in a
      sustained manner. The released drug successfully retained its biological effects
      including anti-inflammatory and anti-protease activity, indicating no interaction
      between the drug and the formulated hydrogel. It was shown that the formulated
      hydrogels could be safely used as a dermal patch for the sustained drug release
      of Paracetamol.

PMID- 29217185
TI  - Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused
      by oxidative stress through autophagy inhibition via PI3K/AKT activation.
AB  - Our previous studies have shown that oxidative stress could promote the porcine
      circovirus type 2 (PCV2) replication, and astragalus polysaccharide
      (APS)/selenium could suppress PCV2 replication. However, whether selenizing
      astragalus polysaccharide (sAPS) provides protection against oxidative stress
      induced PCV2 replication promotion and the mechanism involved remain unclear. The
      present study aimed to explore the mechanism of the PCV2 replication promotion
      induced by oxidative stress and a novel pharmacotherapeutic approach involving
      the regulation of autophagy of sAPS. Our results showed that H2O2 promoted PCV2
      replication via enhancing autophagy by using 3-methyladenine (3-MA) and autophagy
      related gene 5 (ATG5) knockdown. Sodium selenite, APS, the mixture of sodium
      selenite and APS, and sAPS significantly inhibited H2O2-induced PCV2 replication
      promotion, respectively. Among these, sAPS exerted maximal inhibitory effect.
      sAPS could also significantly inhibit autophagy activated by H2O2 and increase
      the Akt and mTOR phosphorylation. Moreover, LY294002, the specific
      phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor, significantly
      alleviated the effects of sAPS on autophagy and PCV2 replication. Taken together,
      we conclude that H2O2 promotes PCV2 replication by inducing autophagy and sAPS
      attenuates the PCV2 replication promotion through autophagy inhibition via
      PI3K/AKT activation.

PMID- 29217186
TI  - Biosynthesis of silver nanoparticles and polyhydroxybutyrate nanocomposites of
      interest in antimicrobial applications.
AB  - This study deals with the optimization and scaling up of the production of poly(3
      hydroxybutyrate), PHB, nanocomposites containing biosynthesized silver
      nanoparticles (AgNPs) to generate materials with antimicrobial performance.
      First, a comparative study of the chemical and biological synthesis of AgNPs
      during the fermentation process of Cupriavidus necator at shake flask-scale was
      carried out. These experiments demonstrated the inherent capacity of C. necator
      to reduce the silver salt and produce AgNPs without the need for adding a
      reducing agent and, that the method of synthesis (with or without reducing agent)
      affects the dispersion of the AgNPs and their antimicrobial performance. Finally,
      the process was scaled-up to a 10Liters bioreactor and the relevant physical
      properties of the PHB-AgNPs nanocomposites pressed into films were determined.
      From the characterization work, the AgNPs were found to be well dispersed and
      distributed into the polymer matrix, having a maximum frequency of particles with
      average diameter of 76-95nm. Moreover, the presence of AgNPs did not cause any
      effect on the thermal properties of the biopolymer, although a slight reduction
      in crystallinity was seen. The developed materials presented a strong
      antimicrobial activity against the food-borne pathogens Salmonella enterica and
      Listeria monocytogenes, which makes them potentially suitable for active coatings
      and packaging applications. Complete biodisintegration of the samples occurred
      during composting conditions within the first 40days. Interestingly, the presence
      of the AgNPs did not impair the profile of biodegradation of the microbial
      polymer.

PMID- 29217187
TI  - Epidemiologic surveillance of multidrug-resistant bacteria in a teaching
      hospital: A 3-year experience.
AB  - BACKGROUND: The objective of this prospective study was to verify the
      effectiveness of a multidisciplinary surveillance program that was implemented in
      a teaching hospital in southern Brazil, to prevent and control the spread of
      multidrug-resistant organisms. METHODS: The program implemented involved
      establishment of prevention guidelines, hand-hygiene promotion, isolation of
      patients colonized or infected by such organisms, enforced contact precautions,
      and terminal cleaning and disinfection of isolation rooms. A microbiology
      service, previously provided by an external laboratory, was established in the
      hospital. Detection of bacteria-resistant genes and molecular typing were
      performed also. RESULTS: Statistically significant differences were observed
      between the pre- and post-intervention periods (P = .00198). Control measures
      were effective in blocking the dissemination of a previously endemic clone of
      Acinetobacter baumannii. Changes were observed in the dissemination pattern, from
      a monoclonal to a polyclonal mode. The incidence of vancomycin-resistant
      Enterococcus during the surveillance period was low. Only 2 isolates of BLAKPC
      positive Klebsiella pneumoniae (distinct profiles), and 5 isolates of BLASPM
      positive Pseudomonas aeruginosa (a single cluster), were detected. CONCLUSIONS:
      These results indicate that the surveillance program implemented was effective in
      preventing the spread of multidrug-resistant organisms in the hospital.

PMID- 29217188
TI  - HPV vaccinations in low- and middle-income countries.

PMID- 29217189
TI  - An unusual racemic C12-norabietane diterpene and a new abietane diterpene
      alkaloid from Salvia miltiorrhiza Bunge.
AB  - A rare C12-norabietane diterpene racemate (1) and a new abietane diterpene
      alkaloid (2) were isolated from the roots of Salvia miltiorrhiza Bunge. Their
      structures were established by comprehensive spectroscopic analyses, and 1 was
      successfully resolved by chiral HPLC, demonstrating that 1 is racemic. The
      absolute configurations of 1a [(+)-miltiorolide A], 1b [(-)-miltiorolide A], and
      2 were determined using TDDFT-ECD calculations. 1a and 1b are the first examples
      of enantiomeric C12-norabietane diterpenes featuring an isobutylene with a
      tetrahydronaphthalene-butyrolactone ring system. The cytotoxic activities of the
      isolates (1 and 2) were evaluated against three human cancer cell lines BEL-7402,
      HT-29 and PANC-28. A plausible biogenetic pathway of 1 was also proposed.

PMID- 29217190
TI  - The down-regulation of cardiac contractile proteins underlies myocardial
      depression during sepsis and is mitigated by carbon monoxide.
AB  - The aim of this study is to investigate the mechanism underling cardiac
      dysfunction during sepsis, as well as the possible amelioration of this
      dysfunction by exogenous carbon monoxide (CO) administration. For this purpose,
      rats (six-week-old, male, Sprague-Dawley) were administered LPS (15 mg/kg body
      weight, i.p. 6 h) and/or CORM (30 mg/kg, i.p.). The decreased left ventricular
      ejection fraction (EF) observed in LPS group rats was recovered in the LSP + CORM
      group, confirming the protective role of CO against sepsis-induced myocardial
      depression. Proteomic as well as immunoblot analysis showed that the levels of
      myosin heavy and light chains (MHC and MLC) as well as alpha-cardiac actin (ACTC)
      were decreased in the LPS group, and these decreases were mitigated in the LSP +
      CORM group, suggesting that the amounts of major contractile proteins are
      decreased in depressed myocardium. Not only LPS-induced inflammatory cytokine
      (TNFalpha and IL-1beta) production but also the decrease in myofilament proteins
      was mitigated by CORM. These results confirm the protective action of exogenously
      administered CO against myocardial depression during sepsis, and reveal a novel
      mechanism underling cardiac dysfunction during sepsis.

PMID- 29217192
TI  - AMOT is required for YAP function in high glucose induced liver malignancy.
AB  - AMOT has been identified as a YAP interactor. However, how AMOT regulates YAP
      remains unclear and controversy. Here, we identified that besides YAP, AMOT was
      another Hippo signaling core factor which could be O-GlcNAcylated. Moreover, high
      glucose (HG) was able to enhance the expression and O-GlcNAcylation of AMOT. We
      also found that HG stimulated nuclear accumulation, transcription activity,
      interaction with transcription factor and transcription of target genes of YAP
      via AMOT, while AMOT acted as a suppressor of YAP in normal glucose level.
      Finally, we observed the upregulation and nuclear accumulation of AMOT and YAP in
      Streptozocin (STZ) induced high glucose mice. Collectively, we have uncovered
      that AMOT acts as a YAP stimulator in high glucose level. Targeting the
      aberrantly regulated core factors in Hippo pathway might be a more effective
      therapeutic approach for liver cancer associated with possibly diabetes.

PMID- 29217191
TI  - TNF-alpha induces expression of the circadian clock gene Bmal1 via dual calcium
      dependent pathways in rheumatoid synovial cells.
AB  - Tumor necrosis factor (TNF)-alpha is responsible for expressions of several clock
      genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal
      fluctuation. We tried to determine the mechanism involved in over-expression of
      Bmal1, induced by TNF-alpha, in primary cultured rheumatoid synovial cells. Cells
      were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor
      FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or
      transfected with p300 and CBP small interfering RNA (siRNA) before stimulation
      with TNF-alpha. Oscillation phase and amplitude of Bmal1, transcriptional
      activator Roralpha, transcriptional repressor Rev-erbalpha, and histone
      acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR.
      As results, TNF-alpha did not influence the oscillation phase of Rev-erbalpha,
      while enhanced those of Roralpha, resulting in over-expression of Bmal1. When
      Ca2+ influx was inhibited by BAPTA-AM, TNF-alpha-mediated up-regulation of
      Roralpha was cancelled, however, that of Bmal1 was still apparent. When we
      further explored another pathway between TNF-alpha and Bmal1, TNF-alpha
      suppressed the expression of Rev-erbalpha in the absence of Ca2+ influx, as well
      as those of p300 and Cbp genes. Finally, actions of TNF-alpha, in increasing
      Bmal1/Roralpha and decreasing Rev-erbalpha, were cancelled by C646 treatment or
      silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF
      alpha in inducing Bmal1 via dual calcium dependent pathways; Roralpha was up
      regulated in the presence of Ca2+ influx and Rev-erbalpha was down-regulated in
      the absence of that. Results proposed that inhibition of p300/CBP could be new
      therapeutic targets for RA.

PMID- 29217193
TI  - Regulation of inflammatory gene expression in macrophages by epithelial-stromal
      interaction 1 (Epsti1).
AB  - Epithelial-stromal interaction 1 (EPSTI1) was first discovered as a gene induced
      in breast cancer epithelial cells by co-cultured stromal fibroblasts. There are
      many reports on the role of Epsti1 in cancer malignancy. Epsti1 is now well known
      in regulating cancer. Recently, the role of Epsti1 in the immune response has
      been reported; these reports suggest the role of Epsti1 in immune function,
      immune privilege, and autoimmune diseases. Furthermore, they show that Epsti1 is
      expressed in various types of immune cells. In this study, we observed that
      Epsti1 is highly expressed in macrophages exposed to IFNgamma and
      lipopolysaccharide (LPS), which classically activates macrophages. Polarization
      of macrophage to classically activated (M1) or alternatively activated (M2) is
      important for mounting responses against various infections. The M1 and M2 types
      of macrophage have a distinct role in the immune system. However, the molecular
      mechanism of modulation of the macrophage type is not well defined. Our results
      showed that the M2 type macrophage phenotype is enhanced in Epsti1-deficient bone
      marrow-derived macrophages (BMDM). In addition, Epsti1 deficiency suppresses
      induction of pro-inflammatory genes in BMDMs via inhibition of Stat1 and p65
      nuclear localization and phosphorylation. Surprisingly, Epsti1-/- mice show
      decreased numbers of M1 macrophages in the peritoneal cavity. These findings
      identify Epsti1 as a modulator of macrophage activation and polarization via the
      Stat1 and p65 pathways, and suggest a potentially important role of Epsti1 in
      immunotherapies against inflammatory diseases.

PMID- 29217194
TI  - Long noncoding RNA SNHG15 promotes human breast cancer proliferation, migration
      and invasion by sponging miR-211-3p.
AB  - Long non-coding RNAs (lncRNA) have been demonstrated to act as essential
      regulators in the development and progression of breast cancer. In our study, we
      found that long noncoding RNA SNHG15 was highly expressed in breast cancer
      tissues and cell lines. And the expression of SNHG15 was correlated with TNM
      stage, lymphnode metastasis and survival in breast cancer patients. SNHG15
      knockdown significantly inhibited the proliferation and induced apoptosis in
      breast cancer cells in vitro and in vivo. Besides, SNHG15 downregulation
      suppressed cell migration and invasion in MCF-7 and BT-20 cells, and inhibited
      epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG15 acted
      as a competing endogenous RNA to sponge miR-211-3p, which was downregulated in
      breast cancers and inhibited cell proliferation and migration. Our results showed
      that there was a negative correlation between SNHG15 and miR-211-3p expression in
      breast cancer patients. Collectively, we, for the first time, revealed the
      functions of SNHG15 and miR-211-3p in breast cancer.

PMID- 29217195
TI  - Calmodulin-dependent protein kinase II (CaMKII) mediates radiation-induced
      mitochondrial fission by regulating the phosphorylation of dynamin-related
      protein 1 (Drp1) at serine 616.
AB  - Mitochondrial dynamics are suggested to be indispensable for the maintenance of
      cellular quality and function in response to various stresses. While ionizing
      radiation (IR) stimulates mitochondrial fission, which is mediated by the
      mitochondrial fission protein, dynamin-related protein 1 (Drp1), it remains
      unclear how IR promotes Drp1 activation and subsequent mitochondrial fission.
      Therefore, we conducted this study to investigate these concerns. First, we found
      that X-irradiation triggered Drp1 phosphorylation at serine 616 (S616) but not at
      serine 637 (S637). Reconstitution analysis revealed that introduction of wild
      type (WT) Drp1 recovered radiation-induced mitochondrial fission, which was
      absent in Drp1-deficient cells. Compared with cells transfected with WT or S637A
      Drp1, the change in mitochondrial shape following irradiation was mitigated in
      S616A Drp1-transfected cells. Furthermore, inhibition of CaMKII significantly
      suppressed Drp1 S616 phosphorylation and mitochondrial fission induced by IR.
      These results suggest that Drp1 phosphorylation at S616, but not at S637, is
      prerequisite for radiation-induced mitochondrial fission and that CaMKII
      regulates Drp1 phosphorylation at S616 following irradiation.

PMID- 29217196
TI  - Short-term exposure to dim light at night disrupts rhythmic behaviors and causes
      neurodegeneration in fly models of tauopathy and Alzheimer's disease.
AB  - The accumulation and aggregation of phosphorylated tau proteins in the brain are
      the hallmarks for the onset of Alzheimer's disease (AD). In addition, disruptions
      in circadian rhythms (CRs) with altered sleep-wake cycles, dysregulation of
      locomotion, and increased memory defects have been reported in patients with AD.
      Drosophila flies that have an overexpression of human tau protein in neurons
      exhibit most of the symptoms of human patients with AD, including locomotion
      defects and neurodegeneration. Using the fly model for tauopathy/AD, we
      investigated the effects of an exposure to dim light at night on AD symptoms. We
      used a light intensity of 10 lux, which is considered the lower limit of light
      pollution in many countries. After the tauopathy flies were exposed to the dim
      light at night for 3 days, the flies showed disrupted CRs, altered sleep-wake
      cycles due to increased pTau proteins and neurodegeneration, in the brains of the
      AD flies. The results indicate that the nighttime exposure of tauopathy/AD model
      Drosophila flies to dim light disrupted CR and sleep-wake behavior and promoted
      neurodegeneration.

PMID- 29217197
TI  - Effect of lncRNA HOXA11-AS1 on adipocyte differentiation in human adipose-derived
      stem cells.
AB  - AIMS: To determine the role of lncRNA HOXA11-AS1 on adipocyte differentiation.
      METHODS: Human adipose-derived stem cells (hADSCs) were isolated from adipose
      tissues of patients and cultured in vitro, followed by knockdown of HOXA11-AS1.
      Then, adipocyte differentiation and expression of adipogenic-related genes (CEBP
      alpha, DGAT2, CIDEC, and perilipin) were measured by RT-qPCR and Western blot.
      RESULTS: We demonstrated that knockdown of HOXA11-AS1 inhibited adipocyte
      differentiation, leading to suppression of adipogenic-related gene (CEBP-alpha,
      DGAT2, CIDEC, and perilipin) transcription, as well as decreased lipid
      accumulation in hADSCs. In addition, lncRNA HOXA11-AS1 was highly expressed in
      obese patients and significantly increased during the process of adipocyte
      differentiation. CONCLUSION: The results provide new insight into the molecular
      mechanism by which lncRNA HOXA11-AS1 is involved in adipogenesis and may have
      implications for the treatment of obesity and associated disorders.

PMID- 29217198
TI  - Clinical, Molecular, and Computational Analysis in two cases with mitochondrial
      encephalomyopathy associated with SUCLG1 mutation in a consanguineous family.
AB  - Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated
      with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This
      disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (alpha
      subnit) and SUCLA2 (beta subnit). We report here, two Tunisian patients belonging
      to a consanguineous family with mitochondrial encephalomyopathy, hearing loss,
      lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria.
      Mutational analysis of SUCLG1 gene showed, for the first time, the presence of
      c.41T > C in the exon 1 at homozygous state. In-silico analysis revealed that
      this mutation substitutes a conserved methionine residue to a threonine at
      position 14 (p.M14T) located at the SUCLG1 protein mitochondrial targeting
      sequence. Moreover, these analysis predicted that this mutation alter stability
      structure and mitochondrial translocation of the protein. In Addition, a decrease
      in mtDNA copy number was revealed by real time PCR in the peripheral blood
      leukocytes in the two patients compared with controls.

PMID- 29217199
TI  - Efficient generation of transgene- and feeder-free induced pluripotent stem cells
      from human dental mesenchymal stem cells and their chemically defined
      differentiation into cardiomyocytes.
AB  - Advance in stem cell research resulted in several processes to generate induced
      pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study,
      the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs)
      including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed
      from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus
      carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited
      the characteristics of the classical morphology with human embryonic stem cells
      (hESCs) without integration of foreign genes, indicating the potential of their
      clinical application. Moreover, induced PSCs showed the capacity of self-renewal
      and differentiation into cardiac myocytes. We have achieved the differentiation
      of hiPSCs to cardiomyocytes lineage under serum and feeder-free conditions, using
      a chemically defined medium CDM3. In CDM3, hiPSCs differentiation is highly
      generating cardiomyocytes. The results showed this protocol produced contractile
      sheets of up to 97.2% TNNT2 cardiomyocytes after purification. Furthermore,
      derived hiPSCs differentiated to mature cells of the three embryonic germ layers
      in vivo and in vitro of beating cardiomyocytes. The above whole protocol enables
      the generation of large scale of highly pure cardiomyocytes as needed for
      cellular therapy.

PMID- 29217201
TI  - Expression and purification of the human epidermal growth factor receptor
      extracellular domain.
AB  - In the fields of drug discovery and protein science, small quantities of proteins
      are always needed to investigate or validate protein-protein (or protein-small
      molecule) interactions. Traditional transient or stable expression method to
      obtain recombinant proteins in eukaryotic systems can be laborious and time
      consuming, especially when multiple protein variants are required. Here, we
      present a fast and convenient method for obtaining small quantities of
      recombinant human epidermal growth factor receptor (rhEGFR) ectodomain protein,
      which could be efficiently extended to the expression of other eukaryotic
      proteins. Human EGFR ectodomain gene was inserted into the plasmid pBMN-GFP and
      recombinant plasmid was transfected into HEK 293 T cells. In the presence of
      hygromycin, cells with the integrated human EGFR ectodomain gene were selected
      and proliferated. rhEGFR ectodomain in cell culture supernatant was purified
      using serial connected diethylaminoethyl Sepharose column and Ni-NTA Sepharose
      column. Purity of the final purified rhEGFR ectodomain was over 95% according to
      SDS-PAGE analysis. Moreover, the purified target protein was biological active
      via measuring the affinity between the rhEGFR ectodomain and rhEGF. Our method
      could greatly facilitate research in the areas of protein science, protein
      structural biology, and drug discovery.

PMID- 29217202
TI  - Cell-free production, purification and characterization of human mitochondrial
      ADP/ATP carriers.
AB  - Mitochondrial Carriers (MCs) are responsible for fluent traffic of a variety of
      compounds that need to be shuttled via mitochondrial inner membranes to maintain
      cell metabolism. The ADP/ATP Carriers (AACs) are responsible for the import of
      ADP inside the mitochondria and the export of newly synthesized ATP. In human,
      four different AACs isoforms are described which are expressed in tissue-specific
      manner. They are involved in different genetic diseases and play a role in
      cancerogenesis. Up to now only the structures of the bovine (isoform 1) and yeast
      (isoforms 2 and 3) AAC have been determined in one particular conformation,
      obtained in complex with the CATR inhibitor. Herein, we report that full-length
      human ADP/ATP Carriers isoform 1 and 3 were successfully expressed in cell-free
      system and purified in milligram amounts in detergent-solubilized state. The
      proteins exhibited the expected secondary structure content. Thermostability
      profiles showing stabilization by the CATR inhibitor suggest that the carriers
      are well folded.

PMID- 29217200
TI  - Timing is everything: Reiterative Wnt, BMP and RA signaling regulate
      developmental competence during endoderm organogenesis.
AB  - A small number of signaling pathways are used repeatedly during organogenesis,
      and they can have drastically different effects on the same population of cells
      depending on the embryonic stage. How cellular competence changes over
      developmental time is not well understood. Here we used Xenopus, mouse, and human
      pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and
      retinoic acid (RA) signals regulates endoderm developmental competence and organ
      induction, focusing on respiratory fate. While Nkx2-1+ lung fate is not induced
      until late somitogenesis stages, here we show that lung competence is restricted
      by the gastrula stage as a result of Wnt and BMP-dependent anterior-posterior (A
      P) patterning. These early Wnt and BMP signals make posterior endoderm refractory
      to subsequent RA/Wnt/BMP-dependent lung induction. We further mapped how RA
      modulates the response to Wnt and BMP in a temporal specific manner. In the
      gastrula RA promotes posterior identity, however in early somite stages of
      development RA regulates respiratory versus pharyngeal potential in anterior
      endoderm and midgut versus hindgut potential in posterior endoderm. Together our
      data suggest a dynamic and conserved response of vertebrate endoderm during
      organogenesis, wherein early Wnt/BMP/RA impacts how cells respond to later
      Wnt/BMP/RA signals, illustrating how reiterative combinatorial signaling can
      regulate both developmental competence and subsequent fate specification.

PMID- 29217203
TI  - Effect of milling on the plastic and the elastic stiffness of lactose particles.
AB  - The purpose of this study was to investigate the effect of degree of disorder of
      a series of alpha-lactose monohydrate powders, prepared by milling for different
      time periods, on the plastic and the elastic stiffness of the particles. As
      references, a series of physical mixtures consisting of original crystalline
      particles and amorphous particles obtained by spray-drying was used. In addition,
      the effect of powder pre-storage humidity on the mechanical properties was
      investigated. For milled particles of a low degree of disorder, a decreased
      particle size increased the particle plastic stiffness. For milled particles of
      constant particle size, the plastic stiffness decreased with an increased degree
      of disorder while the elastic stiffness seemed nearly independent of the degree
      of disorder. The presence of moisture caused a recrystallisation of milled
      particles with low degree of disorder which increased their plastic stiffness.
      For the physical mixtures of crystalline and amorphous particles, similar
      relationships between plastic stiffness and amorphous content as for the milled
      powders were obtained. A reasonable explanation is that the nature of the milled
      particles is represented by a two-state system with crystalline and amorphous
      domains.

PMID- 29217204
TI  - Appropriateness and Complications of Peripheral Venous Catheters Placed in an
      Emergency Department.
AB  - BACKGROUND: The insertion of peripheral venous catheters (PVCs) is the invasive
      procedure most frequently performed in hospitals, and it could be associated with
      complications. The appropriateness of PVC placement, however, has not been
      carefully analyzed. OBJECTIVES: We conducted a study to assess the rate of PVC
      placement in our Emergency Department (ED), their use, their immediate or
      potential usefulness, and their complications. METHODS: In this descriptive
      prospective study, we recorded every PVC placed in our ED during 1 week and
      assessed its appropriateness in terms of its use and potential usefulness. We
      then followed the patients transferred to medical wards to determine the duration
      of PVC maintenance and any complications. RESULTS: PVCs (n = 210) were placed for
      34% (n = 207) of the 605 patients admitted to the ED during the study period. Of
      these PVCs, 27% (n = 52) were not used and 43% (n = 91) were considered
      ineffective. Follow-up covered 92 patients with PVCs transferred to medical
      wards. We recorded seven episodes of phlebitis (8%) and no infections, local or
      systemic. The mean duration of PVS maintenance in the medical wards was 40 h from
      insertion. Of the PVCs with complications, 43% were ineffective. The mean
      duration of maintenance of the PVCs that led to complications was 80 h, compared
      with 35 h for those without complications (p < 0.02). CONCLUSION: In accordance
      with the literature, half of the PVCs inserted in our ED were ineffective; half
      the PVCs causing complications were avoidable.

PMID- 29217206
TI  - Comments On The Treatment Of Resistant Tuberculosis.

PMID- 29217205
TI  - Increased Urinary Erythropoietin Excretion in Severe Sleep Apnea-Hipoapnea
      Syndrome: The Effect of CPAP.
AB  - INTRODUCTION: Tissue hypoxia stimulates the production of erythropoietin (EPO),
      the main effect of which is, in turn, to stimulate erythropoiesis. Sleep apnea
      hypopnea syndrome (SAHS) is an entity characterized by repeated episodes of
      hypoxemia during sleep. OBJECTIVE: To analyze whether hypoxemia stimulated
      increased urinary excretion of EPO, and if so, to evaluate if treatment with
      continuous positive airway pressure (CPAP) can inhibit this phenomenon. METHODS:
      We studied 25 subjects with suspected SAHS who underwent a polysomnography study
      (PSG). EPO levels in first morning urine (uEPO) and blood creatinine and
      hemoglobin were determined in all patients. Patients with severe SAHS repeated
      the same determinations after CPAP treatment. RESULTS: Twelve subjects were
      diagnosed with severe SAHS (mean +/- SD, AHI 53.1 +/- 22.7). Creatinine and
      hemoglobin levels were normal in all subjects. uEPO was 4 times higher in the
      SAHS group than in the control group (1.32 +/- 0.83 vs. 0.32 +/- 0.35 UI/l, p
      <.002). CPAP treatment reduced uEPO to 0.61 +/- 0.9 UI/l (p <.02), levels close
      to those observed in healthy subjects. No dose-response relationship was observed
      between severity of PSG changes and uEPO values. CONCLUSIONS: Patients with
      severe SAHS show increased uEPO excretion, but this normalizes after treatment
      with CPAP.

PMID- 29217207
TI  - More Platon And Less Prozac: The Arrival Of ASTHMA-ZUMAB.

PMID- 29217208
TI  - Anisocoria Associated With Spontaneous Pneumomediastinum.

PMID- 29217209
TI  - Non-Invasive Ventilation In Non-COPD Subjects With Pneumonia: Benefits And
      Potential Complications.

PMID- 29217210
TI  - Smoking In COPD Patients: A New Clinical Phenotype?

PMID- 29217211
TI  - Mediating effects of cancer risk factors on the association between race and
      cancer incidence: analysis of the NIH-AARP Diet and Health Study.
AB  - PURPOSE: Racial disparities exist in the prevalence of cancer-related risk
      factors and incidence of cancer. The objective of this study is to determine if
      cancer-related risk factors mediate the association between race and cancer
      incidence. METHODS: We performed prospective analysis of data from the National
      Institutes of Health-American Association of Retired Persons Diet and Health
      Study, years 1995 through 2011. We compared differences in baseline
      characteristics between black and white participants using chi2 tests and
      Wilcoxon tests, as appropriate. We determined risk of any cancer and the most
      common cancer types (i.e., breast, prostate, and colorectal) using Cox
      Proportional hazards models, adjusted for age, sex, marital status, education,
      health status, region, and adherence to guidelines on cancer-related risk factors
      (i.e., body mass index [BMI], smoking status, physical activity, nutrition, and
      alcohol consumption). We examined the mediation effect of cancer-related risk
      factors on the association between race and cancer incidence. RESULTS: Among
      425,152 participants, 16,110 (3.79%) were black, and 409,042 (96.21%) were white.
      The white participants were more likely to be aged 65 years and older (35.33% vs.
      25.93%), male (60.88% vs. 42.67%), married (70.37% vs. 48.26%), reside in Western
      US (30.14% vs. 23.88%), be physically active (46.72% vs. 41.94%), and have higher
      adherence scores (3.14 vs. 3.04). Blacks had reduced risk of breast cancer
      (adjusted hazard ratio [HR]: 0.82, 95% confidence intervals [CI]: 0.74-0.90) but
      higher risk of prostate (adjusted HR: 1.86, 95% CI: 1.75-1.98) and colorectal
      cancer (adjusted HR: 1.17, 95% CI: 1.05-1.31) compared with whites. Nutrition
      mediated the association between race and breast cancer (6.35% mediated, P <
      .01), whereas BMI mediated the association between race and colorectal cancer
      (7.99% mediated, P < .01). CONCLUSIONS: Blacks were at reduced risk of breast
      cancer but increased risks for prostate and colorectal cancer incidence.
      Nutrition and BMI exerted small but significant mediating effects on the racial
      disparity in risk of breast and colorectal cancers, respectively.

PMID- 29217212
TI  - Ovarian Morphology by Transabdominal Ultrasound Correlates With Reproductive and
      Metabolic Disturbance in Adolescents With PCOS.
AB  - PURPOSE: To determine whether ovarian morphology imaged using transabdominal
      ultrasonography reflects clinical and metabolic features in adolescents with
      polycystic ovary syndrome (PCOS). METHODS: A retrospective pilot study was
      conducted in 33 adolescents (12-18 years) with PCOS as defined by
      hyperandrogenism and irregular cycles. Adolescents underwent the following
      assessments at a random time during the menstrual cycle: transabdominal
      ultrasonography, physical examination (height, weight, and systolic and diastolic
      blood pressure), fasting hormonal tests (free, percent free, and total
      testosterone, androstenedione, follicle stimulating hormone, luteinizing
      hormone), and metabolic tests (including an oral glucose tolerance test, fasting
      and 2-hour insulin and glucose, homeostatic model assessment of insulin
      resistance, and whole-body insulin sensitivity index). Ultrasound images were
      analyzed offline for ovarian area (OA), ovarian volume (OV), follicle number per
      cross section (FNPS), and follicle distribution pattern. Associations among
      endocrine and metabolic variables with sonographic features were assessed by
      Spearman's rank correlation coefficients and stepwise multiple linear regression.
      RESULTS: Total testosterone and androstenedione, but not free testosterone, or
      percent free testosterone, positively correlated with OA (rho = .515, rho = .422,
      respectively), OV (rho = .451, rho = .382), and FNPS (rho = .394, rho = .474).
      Luteinizing hormone:follicle stimulating hormone ratio also positively correlated
      with ovarian size (OA, rho = .520 and OV, rho = .409). Unexpectedly, body mass
      index (rho = -.503) and fasting glucose levels (rho = -.393) were inversely
      correlated with FNPS. Total testosterone was an independent predictor of FNPS,
      OA, and OV as judged by stepwise multiple regression analyses. CONCLUSIONS: Some
      aspects of ovarian morphology in adolescents with PCOS using transabdominal
      ultrasonography associate with markers of reproductive dysfunction and provide
      rationale to further investigate how ovarian morphology may reflect concurrent
      metabolic dysfunction.

PMID- 29217213
TI  - Adolescent Sexual Risk Taking: The Distribution of Youth Behaviors and Perceived
      Peer Attitudes Across Neighborhood Contexts.
AB  - PURPOSE: Sexual activity is a normative part of adolescent development, yet early
      sexual debut and sex with multiple partners undermine health and well-being. Both
      structural (e.g., poverty) and social (e.g., norms) characteristics of
      neighborhoods shape sexual risk taking, yet scholarship remains focused on urban
      areas. Thus, this study explores sexually permissive attitudes and sexual risk
      taking across a wider expanse of neighborhood types. METHODS: Among 8,337
      nonsexually active respondents in Wave I (1994-1995 [ages 11-18]) of the National
      Longitudinal Study of Adolescent to Adult Health (Add Health), a hierarchical
      linear model and a hierarchical generalized linear model were used to estimate
      the effect of neighborhood type and permissive sexual climate on youths' sexual
      debut, age at debut, and lifetime number of sexual partners by Wave III (2001
      2002 [ages 18-26]), controlling for individual, familial, and peer factors.
      RESULTS: Sexual climates varied in overall permissiveness and internal
      consistency both across and within neighborhood types and were linked to
      increased sexual risk taking. Compared with youth from upper middle class white
      suburbs, the odds of sexual debut and the number of partners were highest among
      youth from rural (black and white) neighborhoods; youth from almost all other
      neighborhood types initiated sex earlier. CONCLUSIONS: Early sexual debut in
      adolescence is a public health issue with immediate and long-term implications.
      Adolescence unfolds in neighborhood environments, the characteristics of which
      may spur youth into such risk taking. Continued scholarship on sexual risks
      should consider further variations in the geographic distributions of such risks
      to investigate more fully their consequences.

PMID- 29217215
TI  - Relationship between hallucination proneness and musical aptitude is mediated by
      microstructure in the corpus callosum.

PMID- 29217214
TI  - Reducing Physical Violence Toward Primary School Students With Disabilities.
AB  - PURPOSE: We tested whether the Good School Toolkit reduces physical violence from
      peers and school staff toward students with and without disabilities in Ugandan
      primary schools. METHODS: We conducted a cluster randomized controlled trial,
      with data collected via cross-sectional surveys in 2012 and 2014. Forty-two
      primary schools in Luwero District, Uganda, were randomly assigned to receive the
      Good School Toolkit for 18 months, or to a waitlisted control group. The primary
      outcome was past week physical violence from school staff, measured by primary 5,
      6, and 7 students' (aged 11-14 years) self-reports using the International
      Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool
      Child Institutional. Disability was assessed through the six Short Set Washington
      Group questions on functioning. Analyses were by intention to treat. RESULTS: At
      endline, 53% of control group students with no functional difficulties reported
      violence from peers or school staff, versus 84% of students with a disability.
      Prevalence of past week physical violence from school staff was lower in
      intervention schools than in the control schools after the intervention, in
      students with no functional difficulties (adjusted odds ratio [aOR] = .41, 95%
      confidence interval [CI .26-.65]), students with some functional difficulties
      (aOR = .36, 95% CI .21-.63), and students with disabilities (aOR = .29, 95% CI
      .14-.59). The intervention also reduced violence from peers in young adolescents,
      with no evidence of a difference in effect by disability status. CONCLUSIONS: The
      Good School Toolkit is an effective intervention to reduce violence perpetrated
      by peers and school staff against young adolescents with disabilities in Ugandan
      primary schools.

PMID- 29217216
TI  - Corrigendum to "Expression of polymeric immunoglobulin receptor and stromal
      activity in pancreatic ductal adenocarcinoma" [Pancreatology 17 (2017) 295-302].

PMID- 29217218
TI  - Nature-based solutions for resilient landscapes and cities.
AB  - Nature-based solutions (NBS) are increasingly applied to guide the design of
      resilient landscapes and cities to enable them to reach economic development
      goals with beneficial outcomes for the environment and society. The NBS concept
      is closely related to other concepts including sustainability, resilience,
      ecosystem services, coupled human and environment, and green (blue)
      infrastructure; however, NBS represent a more efficient and cost-effective
      approach to development than traditional approaches. The European Commission is
      actively engaged in investing in NBS as a driver in developing ecosystem services
      based approaches throughout Europe and the world. The pool of knowledge and
      expertise presented in this Special Issue of Environmental Research highlights
      the applications of NBS as 'living' and adaptable tools to boost the capacity of
      landscapes and cities to face today's critical environmental, economic and
      societal challenges. Based on the literature and papers of this Special Issue, we
      propose five specific challenges for the future of NBS.

PMID- 29217217
TI  - Antioxidant Role of Vitamin D in Mice With Alloxan-Induced Diabetes.
AB  - OBJECTIVES: The discovery of vitamin D receptors has revolutionized the
      understanding of vitamin D biology, which is now thought to influence a wide
      array of cell pathways. The antihyperglycemic actions of vitamin D involving
      calcium metabolism have been widely discussed, but studies are now suggesting a
      possibility of vitamin D-induced amelioration of oxidative stress. Despite its
      significance in disease pathogenesis, oxidative status remains poorly
      investigated with respect to vitamin D treatment in the biology of diabetes
      mellitus. The present study was aimed at assessing the antioxidant therapeutic
      potential of vitamin D in diabetes mellitus. METHODS: Balb/c mice were induced to
      experimental diabetes with a single dose of alloxan. Following a 15-day treatment
      period, various parameters pertaining to glucose metabolism, oxidative stress,
      zinc concentration and DNA damage were analyzed. RESULTS: With the exception of
      superoxide dismutase and catalase, the antioxidant enzyme activities were
      slightly altered in various groups. However, improved glucose homeostasis and
      zinc concentration and reduced DNA damage were observed in the group treated with
      vitamin D. CONCLUSIONS: The present work accounts for the ubiquitous roles of
      vitamin D in various diseases and highlights its role as a therapeutic
      intervention in diabetes mellitus.

PMID- 29217219
TI  - Device Closure of a Ventricular Septal Rupture in a Patient on ECMO.

PMID- 29217220
TI  - Transaxillary Implantation of the Impella CP Mechanical Circulatory Support
      Device as a Bridge to Heart Transplant. First Experience in Spain.

PMID- 29217221
TI  - Selection of the Best of 2017 in Clinical Cardiology. Continuum Healthcare
      Between Cardiology and Primary Care.

PMID- 29217222
TI  - Electroacupuncture Reduces Incontinence Episodes in Women With Stress Urinary
      Incontinence.

PMID- 29217223
TI  - Temporal variability of global DNA methylation and hydroxymethylation in buccal
      cells of healthy adults: Association with air pollution.
AB  - BACKGROUND: Epigenetic changes, such as DNA methylation, are observed in response
      to environmental exposure and in the development of several chronic diseases.
      Consequently, DNA methylation alterations might serve as indicators of early
      effects. In this context, the aim of this study was to assess the temporal
      variability of global DNA methylation and hydroxymethylation levels in buccal
      cells from healthy adult volunteers. METHODS: Global DNA methylation (%5mdC) and
      hydroxymethylation (%5hmdC) levels in human buccal cells, collected from 26
      healthy adults at different time points, were quantified by UPLC-MS/MS.
      Associations between %5mdC and %5hmdC, respectively, and short-term exposure (1
      7days) to air pollutants PM2.5 and PM10 were tested with mixed-effects models
      including various covariates. RESULTS/DISCUSSION: Dynamic short-term changes in
      DNA methylation and hydroxymethylation levels in buccal cells were observed,
      which were inversely associated with exposure to PM2.5 and PM10. An IQR increase
      in PM2.5 over a 7-day moving average period was significantly associated with a
      decrease of -1.47% (-1.74%, -1.20%) and -0.043% (-0.054%, -0.032%) in %5mdC and
      %5hmdC, respectively. Likewise, for PM10, a decrease of -1.42% (-1.70, -1.13) and
      -0.040% (-0.051%, -0.028%) was observed. CONCLUSION: Global DNA methylation and
      hydroxymethylatation varied over a time period of three weeks. The observed
      temporal variability was associated with exposure to ambient PM2.5 and PM10
      levels. This should be taken into account when interpreting epigenetic
      alterations in buccal cells.

PMID- 29217224
TI  - The neural correlates of self-referential memory encoding and retrieval in
      schizophrenia.
AB  - BACKGROUND: Enhanced memory for self-oriented information is known as the self
      referential memory (SRM) effect. fMRI studies of the SRM effect have focused
      almost exclusively on encoding, revealing selective engagement of the medial
      prefrontal cortex (mPFC) during "self" relative to other processing conditions.
      Other critical areas for self-processing include ventrolateral prefrontal cortex
      (vlPFC), temporo-parietal junction (TPJ) and posterior cingulate/precuneus
      (PCC/PC). Previous behavioral studies show that individuals with schizophrenia
      fail to benefit from this memory boost. However, the neural correlates of this
      deficit, at either encoding or retrieval, are unknown. METHODS: Twenty
      individuals with schizophrenia and 16 healthy controls completed an event-related
      fMRI SRM paradigm. During encoding, trait adjectives were judged in terms of
      structural features ("case" condition), social desirability ("other" condition),
      or as self-referential ("self" condition). Participants then completed an
      unexpected recognition test (retrieval phase). We examined BOLD activation during
      both encoding and retrieval within mPFC, vlPFC, TPJ, and PCC/PC regions-of
      interest (ROIs). RESULTS: During encoding, fMRI data indicated both groups had
      greater activation during the "self" relative to the "other" condition across
      ROIs. Controls showed this primarily in mPFC whereas patients showed this in
      PCC/PC. During retrieval, fMRI data indicated controls showed differentiation
      across ROIs between "self" and "other" conditions, but patients did not.
      CONCLUSIONS: Results suggest regional differences in the neural processing of
      self-referential information in individuals with schizophrenia, perhaps because
      representation of the self is not as well established in patients relative to
      controls. The current study presents novel findings that add to the literature
      implicating impaired self-oriented processing in schizophrenia.

PMID- 29217225
TI  - Translation and Cross-Cultural Adaptation of Health Assessment Tools.

PMID- 29217226
TI  - Imiquimoid 5%: In Pursuit of New Treatment Regimens for Actinic Keratosis.

PMID- 29217227
TI  - Histoplasmosis: An Emerging Endemic Mycosis.

PMID- 29217228
TI  - Primary Cutaneous Mucormycosis Due to Rhizopus arrhizus in an 8-Year-Old Girl.

PMID- 29217229
TI  - Idiopathic Facial Aseptic Granuloma: Clinical and Ultrasound Findings in 3 Cases.
AB  - Idiopathic facial aseptic granuloma is a typical childhood disease characterized
      by the presence of one or more asymptomatic nodules on the cheek. Although
      pathogenesis remains unclear, the disease is thought to be a type of childhood
      rosacea. It resolves spontaneously, yet it could be confused with other lesions
      that require treatment. We present clinical and ultrasound findings and outcome
      from 3 new cases. In 2 cases, the lesion presented as childhood rosacea.
      Ultrasound revealed a characteristic pattern, with variations depending on the
      stage of development. High-frequency ultrasound can facilitate the differential
      diagnosis and thus obviate unnecessary biopsy or excision.

PMID- 29217230
TI  - How can we find out the perfect admission electrocardiographic parameter to
      predict no-reflow?

PMID- 29217231
TI  - Risk Factors for Radial-to-Femoral Artery Pressure Gradient in Patients
      Undergoing Cardiac Surgery With Cardiopulmonary Bypass.
AB  - OBJECTIVE: To identify risk factors associated with radial-to-femoral pressure
      gradient during cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: This
      is a retrospective, observational study. SETTING: Single specialized
      cardiothoracic hospital in Montreal, Canada. PARTICIPANTS: Consecutive patients
      that underwent heart surgery with CPB between 2005 and 2015 (n = 435).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A radial-to-femoral pressure
      gradient occurred in 146 patients of the 435 patients (34%). Based on the 10,000
      bootstrap samples, simple logistic regression models identified the 17 most
      commonly significant variables across the bootstrap runs. Using these variables,
      a backward multiple logistic model was performed on the original sample and
      identified the following independent variables: body surface area (m2) (odds
      ratio [OR] 0.08, 95% confidence interval [CI] 0.030-0.232), clamping time
      (minutes) (OR 1.01, 95% CI 1.007-1.018), fluid balance (for 1 liter) (OR 0.81,
      95% CI 0.669-0.976), and preoperative hypertension (OR 1.801, 95% CI 1.131
      2.868). CONCLUSION: A radial-to-femoral pressure gradient occurs in 34% of
      patients during cardiac surgery. Patients at risk seem to be of smaller stature,
      hypertensive, and undergo longer and more complex surgeries.

PMID- 29217232
TI  - The Right Answer.

PMID- 29217233
TI  - Pro: Factor Concentrates are Essential for Hemostasis in Complex Cardiac Surgery.

PMID- 29217234
TI  - Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus
      Recombinant Activated Factor VII Administration During Cardiac Surgery.
AB  - OBJECTIVE: To compare outcomes following inactive prothrombin complex concentrate
      (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac
      surgery. DESIGN: Retrospective propensity-matched analysis. SETTING: Academic
      tertiary-care center. PARTICIPANTS: Patients undergoing cardiac surgery requiring
      cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC.
      INTERVENTIONS: Outcomes following intraoperative administration of rFVIIa (263)
      or factor IX complex (72) as rescue therapy to treat bleeding. MEASUREMENTS AND
      MAIN RESULTS: In the 24 hours after surgery, propensity-matched patients
      receiving PCC versus rFVIIa had significantly less chest tube outputs (median
      difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh
      frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion
      rates (26% v 49%, p = 0.027). There were no significant differences between
      propensity-matched groups in postoperative stroke, deep venous thrombosis,
      pulmonary embolism, myocardial infarction, or intracardiac thrombus.
      Postoperative dialysis was significantly less likely in patients administered PCC
      versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7).
      No significant difference in 30-day mortality in patients receiving PCC versus
      rFVIIa was present following propensity matching. CONCLUSIONS: Use of rFVIIa
      versus inactive PCCs was significantly associated with renal failure requiring
      dialysis and increased postoperative bleeding and transfusions.

PMID- 29217235
TI  - Preserved Posterior Mitral Leaflet Mimicking Periannular Mass.

PMID- 29217236
TI  - Accuracy, Precision, and Trending of 4 Pulse Wave Analysis Techniques in the
      Postoperative Period.
AB  - OBJECTIVE: The aim of this study was to analyze the accuracy, precision, and
      trending ability of the following 4 pulse wave analysis devices to measure
      continuous cardiac output: PiCCO2 ([PCCO]; Pulsion Medical System, Munich,
      Germany); LiDCORapid ([LCCO]; LiDCO Ltd, London, UK); FloTrac/Vigileo ([FCCO];
      Edwards Lifesciences, Irvine, CA); and Nexfin ([NCCO]; BMEYE, Amsterdam, The
      Netherlands). DESIGN: Prospective, observational clinical study. SETTING:
      Intensive care unit of a single-center, teaching hospital. PARTICIPANTS: The
      study comprised 22 adult patients after elective coronary artery bypass surgery.
      INTERVENTIONS: Three measurement cycles were performed in all patient durings
      their immediate postoperative intensive care stay before and after fluid loading.
      Hemodynamic measurements were performed 5 minutes before and immediately after
      the administration of 500 mL colloidal fluid over 20 minutes. MEASUREMENTS AND
      MAIN RESULTS: PCCO, LCCO, FCCO, and NCCO were assessed and compared with cardiac
      output derived from intermittent transpulmonary thermodilution (ICO). One hundred
      thirty-two matched sets of data were available for analysis. Bland-Altman
      analysis using linear mixed effects models with random effects for patient and
      trial revealed a mean bias +/-2 standard deviation (%error) of -0.86 +/- 1.41
      L/min (34.9%) for PCCO-ICO, -0.26 +/- 2.81 L/min (46.3%) for LCCO-ICO, -0.28 +/-
      2.39 L/min (43.7%) for FCCO-ICO, and -0.93 +/- 2.25 L/min (34.6%) for NCCO-ICO.
      Bland-Altman plots without adjustment for repeated measurements and replicates
      yielded considerably larger limits of agreement. Trend analysis for all
      techniques did not meet criteria for acceptable performance. CONCLUSIONS: All 4
      tested devices using pulse wave analysis for measuring cardiac output failed to
      meet current criteria for meaningful and adequate accuracy, precision, and
      trending ability in cardiac output monitoring.

PMID- 29217237
TI  - Pharmacokinetics of Magnesium in Cardiac Surgery: Implications for Prophylaxis
      Against Atrial Fibrillation.

PMID- 29217238
TI  - Feasibility and Impact of Focused Intraoperative Transthoracic Echocardiography
      on Management in Thoracic Surgery Patients: An Observational Study.
AB  - OBJECTIVES: Intraoperative focused transthoracic echocardiography (TTE) is
      feasible and has an effect on the management of hemodynamically unstable surgical
      patients. Furthermore, in noncardiac thoracic surgery, TTE might provide
      additional information for hemodynamic treatment. Transthoracic accessibility
      during thoracic surgical interventions is assumed to be difficult. For patients
      positioned on their right side, a modified subcostal transthoracic view might be
      helpful. DESIGN: A prospective observational study. SETTING: Single-center
      university hospital. PARTICIPANTS: The study comprised 105 consecutive patients
      undergoing noncardiac thoracic surgery. INTERVENTIONS: Focused TTE was performed
      during anesthetic induction after intubation for mechanical ventilation.
      Intraoperative focused TTE, after positioning and draping for surgery, was
      attempted again for all 105 patients. Changes in patient management due to the
      results of the TTE were documented and analyzed. MEASUREMENTS AND MAIN RESULTS:
      Presurgical TTE with mechanical ventilation was applied successfully in 98.1% of
      105 patients. Intraoperative imaging was successful in 90 patients (85.7%).
      Results of intraoperative TTE led to the modification of perioperative management
      in 39 patients (37.1%), 20 (22.0%) of these during surgery. CONCLUSIONS: TTE in
      noncardiac thoracic surgery is feasible using a modified subcostal view and has
      an effect on hemodynamic management in a considerable number of patients.

PMID- 29217240
TI  - The Role of Intraoperative Transesophageal Echocardiography in Identifying a
      Fenestrated Occlusion of the Inferior Vena Cava During Pulmonary
      Thromboendarterectomy.

PMID- 29217239
TI  - Morphologic Evaluation of the Mitral Annulus During Displacement of the Heart in
      Off-Pump Coronary Artery Bypass Surgery.
AB  - OBJECTIVE: To evaluate the morphologic changes of the mitral annulus using 3
      dimensional transesophageal echocardiography during heart displacement to expose
      the anastomosis site in off-pump coronary artery bypass surgery (OPCAB). DESIGN:
      Prospective case series. SETTING: Single center, university hospital.
      PARTICIPANTS: The study comprised 34 consecutive patients who underwent OPCAB of
      the left circumflex artery (LCX) and the right coronary artery (RCA).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mitral annulus parameters
      were measured using the Mitral Valve Quantification program after sternotomy
      (physiologic position) and during displacement of the heart to expose the LCX
      (LCX position) and the RCA (RCA position). The height of the mitral annulus was
      significantly lower in the LCX (5.76 +/- 0.90 mm) and RCA (5.92 +/- 0.97 mm)
      positions than in the physiologic position (6.96 +/- 0.99 mm; both p < 0.0001).
      The percent change in the height of the mitral annulus was significantly greater
      in the mitral regurgitation group than in the mitral regurgitation
      nondeterioration group when in the LCX (-16.3% +/- 6.0% v -11.9% +/- 3.3%, p =
      0.0203) and RCA (-16.9% +/- 6.3% v -12.1% +/- 3.8%, p = 0.0207) positions. The
      anteroposterior and intercommissural diameters, annulus perimeter, and surface
      area of the mitral annulus did not differ significantly among all heart
      positions. CONCLUSIONS: The mitral annulus flattened and lost its saddle shape
      without expanding while in the LCX and RCA positions. The greater percent change
      in the height of the mitral annulus may aggravate mitral regurgitation.

PMID- 29217241
TI  - Myocardial Protection in Mitral Valve Surgery: Comparison Between Minimally
      Invasive Approach and Standard Sternotomy.
AB  - OBJECTIVE: To compare antegrade and retrograde cardioplegia administration in
      minimally invasive mitral valve surgery (MIMS) and open mitral valve surgery
      (OMS) for myocardial protection. DESIGN: Retrospective study. SETTING: Tertiary
      care university hospital. PARTICIPANTS: The study comprised 118 patients
      undergoing MIMS and 118 patients undergoing OMS. INTERVENTIONS: The data of
      patients admitted for MIMS from 2006 to 2010 were reviewed. Patients undergoing
      isolated elective OMS from 2004 to 2006 were used as a control group.
      Cardioplegia in the MIMS group was delivered via the distal port of the
      endoaortic clamp and an endovascular coronary sinus catheter positioned using
      echographic and fluoroscopic guidance. Antegrade and retrograde cardioplegia were
      used in OMS. Data regarding myocardial infarction (MI) (creatine kinase [CK]-MB,
      troponin T, electrocardiography); myocardial function; and hemodynamic stability
      were collected. MEASUREMENTS AND MAIN RESULTS: There was no difference in the
      perioperative MI incidence between both groups (1 in each group, p = 0.96). No
      statistically significant difference was found for maximal CK-MB (35.9 ug/L [25.1
      50.1] v 37.9 ug/L [28.6-50.9]; p = 0.31) or the number of patients with CK-MB
      levels >50 ug/L (29 v 33; p = 0.55) or CK-MB >100 ug/L (3 v 4; p = 0.70) between
      the OMS and MIMS groups. However, maximum troponin T levels in the MIMS group
      were significantly lower (0.47 ug/L [0.32-0.79] v 0.65 ug/L [0.45-0.94]; p =
      0.0007). No difference in the incidence of difficult weaning from bypass and
      intra-aortic balloon pump use between the MIMS and OMS groups was found.
      CONCLUSIONS: Antegrade and retrograde cardioplegia administration during MIMS and
      OMS provided comparable myocardial protection.

PMID- 29217242
TI  - Postoperative Pain After Cardiac Surgery: An Open Issue.

PMID- 29217243
TI  - The Power of Perioperative Dexmedetomidine.

PMID- 29217244
TI  - Intraoperative Transesophageal and Postoperative Transthoracic Echocardiographic
      Evaluation of a Mechanical Heart Valve Prosthesis Implanted at Aortic Position.
AB  - OBJECTIVE: The aims of this study were to evaluate the intraoperative
      transesophageal echocardiographic (iTEE) characteristics and Doppler flow profile
      of aortic Chitra heart valve prosthesis (CHVP) under stable hemodynamic and
      loading conditions, and to compare and correlate the iTEE data with the
      postoperative transthoracic echocardiography (TTE) data obtained at 48 hours
      (TTE1) and 3 months (TTE2) after the surgery. DESIGN: Prospective, observational
      study. SETTING: University-level tertiary referral hospital. PARTICIPANTS: Forty
      patients between 18 years and 65 years of age undergoing elective aortic valve
      replacement (AVR) using CHVP during the period January 2015 to August 2016.
      INTERVENTIONS: After obtaining permission from institutional ethics committee, 40
      patients undergoing elective AVR were studied prospectively. The iTEE examination
      was performed in the pre-cardiopulmonary bypass (CPB) and post-CPB period in all
      the study subjects. CHVP was subjected to iTEE two-dimensional (2D) echo, color
      Doppler, and spectral Doppler evaluation under stable hemodynamic and loading
      condition in the post-CPB period after the administration of protamine. The CHVP
      were re-evaluated using TTE in all the patients 48 hours after the surgery (TTE1)
      and 3 months after the surgery (TTE2). The iTEE and postoperative TTE Doppler
      values were compared and correlated. MEASUREMENTS AND MAIN RESULTS: The CHVP
      could be imaged adequately and interrogated with Doppler in all the patients.
      None of the patients had restriction of occluder mobility or unstable seating of
      the valve. The intraoperative flow dependent (peak velocity [PV] and mean
      pressure gradient [MPG]) and less flow dependent (Doppler velocity index,
      acceleration time, acceleration time/ejection time, effective orifice area [EOA]
      and indexed EOA) Doppler parameters of CHVP were measured as per the American
      Society of Echocardiography recommendations. The PV and MPG of CHVP measured by
      iTEE showed no statistical difference (p > 0.05) and were in limits of agreement
      when compared with TTE1 and TTE2 data. CONCLUSION: The iTEE features of CHVP were
      found compliant with the criteria set by the ASE defining normal functioning of
      an aortic valve prosthesis. The iTEE Doppler parameters obtained under stable
      loading conditions strongly predicted the postoperative values of Doppler
      parameters on TTE examination. The iTEE Doppler values can be used as the
      reference values for the postoperative follow up studies.

PMID- 29217245
TI  - Intubated Versus Nonintubated General Anesthesia for Video-Assisted Thoracoscopic
      Surgery - A Case Control Study: A Response.

PMID- 29217246
TI  - Acute Type A Aortic Dissection and Successful Surgical Repair in a Woman at 21
      Weeks Gestational Pregnancy With Maternal and Fetal Survival: A Case Report.

PMID- 29217247
TI  - Right Ventricular Rupture After Extubation of a Patient With an Open Chest.

PMID- 29217248
TI  - Accidental Complete Occlusion of Innominate Artery During Deployment of Thoracic
      Endovascular Aortic Repair Graft Following Hybrid Stage 1 Carotid-carotid Bypass:
      Is it Possible to Avert Consequences of Cerebral Ischemia?

PMID- 29217249
TI  - Successful Use of Serratus and Transversus Thoracic Plane Blocks for Subcutaneous
      Implantable Cardioverter-Defibrillator Placement.

PMID- 29217250
TI  - Reducing the Risk of Cardiac Perforation During Placement of Bicaval Veno-Venous
      Extracorporeal Membrane Oxygenation Cannulae.

PMID- 29217251
TI  - Effectiveness and Safety of Aprotinin Use in Thoracic Aortic Surgery.
AB  - OBJECTIVE: To determine the effectiveness and safety of aprotinin use in adult
      patients undergoing thoracic aortic surgery. DESIGN: Single-center, retrospective
      study. SETTING: All cases performed at a single university hospital.
      PARTICIPANTS: Between January 2004 and December 2014, 846 adult patients
      underwent thoracic aortic surgery. Due to missing or duplicated data on primary
      outcomes, 314 patients were excluded. The final sample of 532 patients underwent
      surgery on the thoracic aorta. INTERVENTIONS: The patients were divided in the
      following 2 groups: 107 patients (20.1%) received aprotinin during the surgery,
      which represented the study group, whereas the remaining 425 patients (79.9%)
      underwent surgery without the use of aprotinin. MEASUREMENTS AND MAIN RESULTS: To
      adjust for patient selection and preoperative characteristics, a propensity score
      matched analysis was conducted. Mean total blood loss at 12 hours after surgery
      was similar between the 2 groups. The blood product transfusion rates did not
      differ in the 2 groups, except for the rate of fresh frozen plasma transfusion
      being significantly higher in the aprotinin group. Re-exploration for bleeding
      and the incidence of a major postoperative bleeding event were similar between
      the groups. Rates of in-hospital mortality, renal failure, and cerebrovascular
      accidents did not show any statistically significant difference. Aprotinin did
      not represent a risk factor for mortality over the long term (hazard ratio 1.14,
      95% confidence interval 0.62-2.08, p = 0.66). CONCLUSIONS: The use of aprotinin
      demonstrated a limited effect in reducing postoperative bleeding and prevention
      of major bleeding events. Aprotinin did not adversely affect early outcomes and
      long-term survival.

PMID- 29217252
TI  - Is It All Just Academic?

PMID- 29217253
TI  - Update on Cardiovascular Implantable Electronic Devices for Anesthesiologists.
AB  - With the advent of "wireless" endocardial pacing, the subcutaneous implantable
      cardioverter defibrillator, and leadless pacemakers comes an added layer of
      complexity to the perioperative management of cardiovascular implantable
      electronic devices (CIED). Since no formal recommendations currently exist for
      these new CIED technologies, preoperative identification of these devices,
      understanding their functionality, and developing an individualized perioperative
      management plan are imperative for the anesthesiologist. The following review is
      intended to provide the background information required to devise a successful
      perioperative management strategy for newer CIEDs.

PMID- 29217254
TI  - Are We Ready for Regional Mobile ECMO Programs?

PMID- 29217256
TI  - Lateral medullary syndrome following injury of the vestibular pathway to the core
      vestibular cortex: Diffusion tensor imaging study.
AB  - OBJECTIVE: The parieto-insular vestibular cortex (PIVC) is a core region of
      vestibular input into regions of the cortex. The vestibular nuclei have
      reciprocal connections with the PIVC. However, little is known about injury of
      the core vestibular pathway to the PIVC in patients with dorsolateral medullary
      infarctions. In this study, using diffusion tensor tractography (DTT), we
      investigated injury of the neural connections between the vestibular nuclei and
      the PIVC in patients with typical central vestibular disorder. METHODS: Eight
      consecutive patients with lateral medullary syndrome and 10 control subjects were
      recruited for this study. To reconstruct the core vestibular pathway to the PIVC,
      we defined the seed region of interest (ROI) as the vestibular nuclei of the pons
      and the target ROI as the PIVC. Fractional anisotropy (FA), mean diffusivity
      (MD), and tract volume were measured. RESULT: The core vestibular pathway to the
      PIVC showed significantly lower tract volume in patients compared with the
      control group (p<0.05). By contrast, other DTI parameters did not show
      significant differences between the patient and control groups (p>0.05).
      CONCLUSION: In conclusion, injury of the core vestibular pathway to the PIVC was
      demonstrated in patients with lateral vestibular syndrome following dorsolateral
      medullary infarcts. We believe that analysis of the core vestibular pathway to
      the PIVC using DTT would be helpful in evaluating patients with lateral medullary
      syndrome.

PMID- 29217257
TI  - Upregulation of BDNF and Interleukin-1beta in rat spinal cord following noxious
      hind paw stimulation.
AB  - The aim of the present study was to investigate the protein levels of BDNF and IL
      1beta in the lumbar dorsal horn of the rat by Western blot analysis following a
      noxious thermal hind paw stimulation. Ten min, 1h and 3h after the combined
      chemical and thermal stimulation an up to 2-fold increase in BDNF and Il-1beta
      protein expression was observed in the lumbar dorsal spinal cord. A pretreatment
      with the opioid analgesic morphine or the glial cell activation inhibitor
      minocycline partly attenuated protein expression. The present findings indicate
      that the BDNF and IL-1beta induction within the dorsal horn may be linked to the
      development of hyperalgesia, and that opioid analgesics and probably inhibitors
      of glial cell activation can prevent sensitization in the pain pathway at spinal
      level.

PMID- 29217255
TI  - Forms and functions of store-operated calcium entry mediators, STIM and Orai.
AB  - Calcium signals arise by multiple mechanisms, including mechanisms of release of
      intracellular stored Ca2+, and the influx of Ca2+ through channels in the plasma
      membrane. One mechanism that links these two sources of Ca2+ is store-operated
      Ca2+ entry, the most commonly encountered version of which involves the
      extensively studied calcium-release-activated Ca2+ (CRAC) channel. The minimal
      and essential molecular components of the CRAC channel are the STIM proteins that
      function as Ca2+ sensors in the endoplasmic reticulum, and the Orai proteins that
      comprise the pore forming subunits of the CRAC channel. CRAC channels are known
      to play significant roles in a wide variety of physiological functions. This
      review discusses the multiple forms of STIM and Orai proteins encountered in
      mammalian cells, and discusses some specific examples of how these proteins
      modulate or mediate important physiological processes.

PMID- 29217258
TI  - Predictive brain networks for major depression in a semi-multimodal fusion
      hierarchical feature reduction framework.
AB  - Major depressive disorder (MDD) is characterized by dysregulation of distributed
      structural and functional networks. It is now recognized that structural and
      functional networks are related at multiple temporal scales. The recent emergence
      of multimodal fusion methods has made it possible to comprehensively and
      systematically investigate brain networks and thereby provide essential
      information for influencing disease diagnosis and prognosis. However, such
      investigations are hampered by the inconsistent dimensionality features between
      structural and functional networks. Thus, a semi-multimodal fusion hierarchical
      feature reduction framework is proposed. Feature reduction is a vital procedure
      in classification that can be used to eliminate irrelevant and redundant
      information and thereby improve the accuracy of disease diagnosis. Our proposed
      framework primarily consists of two steps. The first step considers the
      connection distances in both structural and functional networks between MDD and
      healthy control (HC) groups. By adding a constraint based on sparsity
      regularization, the second step fully utilizes the inter-relationship between the
      two modalities. However, in contrast to conventional multi-modality multi-task
      methods, the structural networks were considered to play only a subsidiary role
      in feature reduction and were not included in the following classification. The
      proposed method achieved a classification accuracy, specificity, sensitivity, and
      area under the curve of 84.91%, 88.6%, 81.29%, and 0.91, respectively. Moreover,
      the frontal-limbic system contributed the most to disease diagnosis. Importantly,
      by taking full advantage of the complementary information from multimodal
      neuroimaging data, the selected consensus connections may be highly reliable
      biomarkers of MDD.

PMID- 29217259
TI  - Gender differences in anomalous subcortical morphology for children with ADHD.
AB  - Although studies showed subtle reductions in brain volume in fronto-striatial
      regions in children with ADHD, there have been limited investigations of volume
      and lateralizaton in subcortical structures and a paucity of exploration of the
      influence of gender on these findings. This study aims to examine morphology of
      subcortical structures and their association with ADHD symptoms in boys and girls
      as compared to their typically-developing (TD) peers. One hundred and eighty five
      children aged 7-14 years with and without ADHD were included from ADHD-200
      Consortium. Results showed that compared to TD boys, boys with ADHD had reduced
      accumbens, amygdala and hippocampus volumes. There were no volumetric differences
      in any structure between ADHD and TD girls. Asymmetry analysis revealed right
      lateralization compressions within the thalamus in ADHD boys relative to TD boys.
      The findings suggest a gender dimorphic pattern of differences in subcortical
      structures in children with ADHD, and a possible neurobiological mechanism where
      boys with ADHD demonstrate increasing difficulties with
      hyperactivity/impulsivity.

PMID- 29217260
TI  - Ontogenesis of the pinealo-retinal neuronal connection in albino rats.
AB  - It was accepted for a long time that in mammals there is only retinofugal
      neuronal connection between the eye and the pineal body (PB). In our previous
      paper we described that nerve cells were present in hamster PB and these neurons
      could establish a reverse connection with the retina through a transsynaptic
      pathway. In adult albino rats neuronal perikarya were not found. In this present
      experiment it was examined whether the lack of these nerve cells in the PB of
      adult rats is the result of an apoptotic phenomenon or the lack of migration
      during the fetal period. Green fluorescence protein expressing pseudorabies
      virus, spreading only in retrograde direction, was injected into the vitreous
      body of rats at various postnatal ages. Virus labeled cell bodies were not
      observed in the PB of adult rats; however, labeling with gradually decreasing
      number of cells was present in animals aged 3-6, 13-14, 20, 35 and 41 postnatal
      days. Injection of virus, spreading in anterograde direction (expressing red
      fluorescence protein), into the PB of young prepubertal animals resulted in
      labeling in the retina. This observation indicates that the pinealo-retinal
      connection in prepubertal period is active. Immunostaining revealed that some of
      the labeled neuronal perikarya showed activated caspase-3 (an apoptotic marker)
      immunoreactivity. Our results clearly show that the neurons migrate to the PB and
      later, during the prepubertal period, they disappear. Caspase-3 immnoreactivity
      indicates that these cells die off by apoptosis.

PMID- 29217261
TI  - Synucleinopathies in neurodegenerative diseases: Accomplices, an inside job and
      selective vulnerability.
AB  - Pathogenesis of degenerative diseases is complex and multifaceted. The disease
      phenotypes depend on the location of injury/damage in the brain networks and
      pathologically are characterized by loss of brain cells. The reason for this loss
      appears to be an accumulation of misfolded and dysfunctional proteins that
      trigger apoptotic cell death. The role of alpha-synuclein mutations, its
      interaction with other proteins and the cellular environment is discussed in the
      context of selective neuron loss.

PMID- 29217262
TI  - Universal etiology, multifactorial diseases and the constitutive model of disease
      classification.
AB  - Infectious diseases are often said to have a universal etiology, while chronic
      and noncommunicable diseases are said to be multifactorial in their etiology. It
      has been argued that the universal etiology of an infectious disease results from
      its classification using a monocausal disease model. In this article, I will
      reconstruct the monocausal model and argue that modern 'multifactorial diseases'
      are not monocausal by definition. 'Multifactorial diseases' are instead defined
      according to a constitutive disease model. On closer analysis, infectious
      diseases are also defined using the constitutive model rather than the monocausal
      model. As a result, our classification models alone cannot explain why infectious
      diseases have a universal etiology while chronic and noncommunicable diseases
      lack one. The explanation is instead provided by the Nineteenth Century germ
      theorists.

PMID- 29217263
TI  - The Dietary Inflammatory Index is associated with elevated white blood cell
      counts in the National Health and Nutrition Examination Survey.
AB  - White blood cells (WBCs) are considered a reliable biomarker of inflammation.
      Elevations in both WBCs and pro-inflammatory cytokines are associated with
      several chronic conditions. Diet is a strong moderator of inflammation and WBCs.
      The purpose of this study was to examine the association between the Dietary
      Inflammatory Index (DII(r)) and WBCs using data from the United States National
      Health and Nutrition Examination Survey (NHANES). NHANES is a cross-sectional
      study that occurs in two-year cycles. Respondents from five cycles (n = 26,046)
      with available data on diet (collected through a single 24-h dietary recall
      [24HR]) and WBCs (derived using the Coulter method) were included. The DII
      (theoretical range is about -8 to +8) was derived from the micro and
      macronutrients calculated from the 24HR. Linear regression models, using survey
      design procedures, were used to estimate adjusted mean WBC (i.e., total,
      lymphocytes, monocytes, and neutrophils) counts and percentages by DII quartiles.
      Among all participants no statistically significant difference in WBCs were
      observed when comparing DII quartile 4 (most pro-inflammatory) to quartile 1
      (most anti-inflammatory). However, a one-unit increase in the DII was associated
      with a 0.028 (1000 per uL) increase in total WBCs (p = .01). Additionally, a
      0.024 increase in neutrophils (p < .01) was observed for a one-unit increase in
      the DII. In the group of participants with normal body mass index (BMI, 18.5-24.9
      kg/m2), those in DII quartile 4 had higher levels of total WBCs compared to
      subjects with normal BMI in DII quartile 1 (7.12 vs. 6.88, p = .01). Similar
      comparisons were observed for monocytes and neutrophils. However, these
      relationships were not observed for participants who were overweight or obese,
      which are pro-inflammatory conditions. Normal-weight individuals consuming more
      pro-inflammatory diets were more likely to have elevated WBCs. Because of its
      cross-sectional design, NHANES cannot inform directly on temporal relations, thus
      limiting causal inference. Future research is needed to examine the impact of
      anti-inflammatory diet adoption on lowering levels of WBCs, in addition to other
      inflammatory mediators.

PMID- 29217264
TI  - The immune strategies of mosquito Aedes aegypti against microbial infection.
AB  - Yellow fever mosquito Aedes aegypti transmits many devastating arthropod-borne
      viruses (arboviruses), such as dengue virus, yellow fever virus, Chikungunya
      virus, and Zika virus, which cause great concern to human health. Mosquito
      control is an effective method to block the spread of infectious diseases. Ae.
      aegypti uses its innate immune system to fight against arboviruses, parasites,
      and fungi. In this review, we briefly summarize the recent findings in the immune
      response of Ae. aegypti against arboviral and entomopathogenic infections. This
      review enriches our understanding of the mosquito immune system and provides
      evidence to support the development of novel mosquito control strategies.

PMID- 29217265
TI  - Metabolism and disposition of arsenic species from controlled oral dosing with
      sodium arsenite in adult female CD-1 mice. I. Pilot study to determine dosing,
      analytical measurements, and sampling strategies.
AB  - Arsenic (As) is ubiquitous in the earth's crust, with typical dietary intake in
      developed countries <1 MUg/kg bw/d, and atypical groundwater exposures in
      developing countries approaching 50 MUg/kg bw/d. Arsenic exposures are linked
      with human diseases and doses of toxicological concern are similar to typical
      dietary intake estimates. The methylation of arsenite by arsenite-3
      methyltransferase (As3MT) promotes the clearance of arsenic as pentavalent
      species, but also generates reactive trivalent intermediates. This study measured
      inorganic arsenic and its metabolites in pentavalent and trivalent states in
      blood, tissues, and excreta after oral administration of arsenite (50-200 MUg/kg
      bw). While liver was a major site for clearance of arsenite and formation of
      methylated species, it also had extensive binding of trivalent intermediates;
      however, thiol exchange and oxidation reactions of trivalent arsenic were facile
      since dimethylarsinic acid (DMAV) was the predominant species in blood and urine.
      Consistent evidence was observed for a non-linear relationship between doses
      above 50 MUg/kg bw and levels of bound trivalent As metabolites. The abundance of
      protein-bound trivalent arsenic within target tissues should correlate with
      disruption of critical cellular processes, which rely on defined interactions of
      thiol functional groups, and could provide dose-response relationships from
      animal models for human risk assessment.

PMID- 29217266
TI  - Auriculasin-induced ROS causes prostate cancer cell death via induction of
      apoptosis.
AB  - Recent studies have demonstrated that natural agents targeting the accumulation
      of reactive oxygen species (ROS) that selectively kill, leaving normal cells
      undamaged, can suppress prostate cancer. Here, we show that auriculasin, derived
      from Flemingia philippinensis, induces significant cell death and apoptosis via
      ROS generation in prostate cancer cells. Auriculasin treatment resulted in
      selective apoptotic cell death in LNCaP prostate cancer cells, characterized by
      DNA fragmentation, accumulation of sub-G1 cell population, cleavage of poly (ADP
      ribose) polymerase (PARP), regulation of Bax/Bcl-2 ratio, increase of cytosolic
      apoptosis-inducing factor (AIF) and endonuclease G (EndoG), in addition to
      inhibiting tumor growth in a xenograft mouse model. Interestingly, auriculasin
      induced apoptosis did not result in caspase-3, -8, and -9 activations. We found
      that auriculasin treatment decreased phosphorylation of AKT/mTOR/p70s6k in a dose
      and time-dependent manner. Further, cellular ROS levels increased in LNCaP cells
      treated with auriculasin and blocking ROS accumulation with ROS scavengers
      resulted in inhibition of auriculasin-induced PARP cleavage, AIF increase,
      upregulation of Bax/Bcl-2 ratio, and decrease in AKT/mTOR phosphorylation. Taken
      together, these data suggest that auriculasin targets ROS-mediated caspase
      independent pathways and suppresses PI3K/AKT/mTOR signaling, which leads to
      apoptosis and decreased tumor growth.

PMID- 29217267
TI  - Mycotoxins in dry-cured meats: A review.
AB  - Dry-cured meats products are consumed in various regions of the world and,
      consumers are increasingly demanding better quality and safety of these products.
      Some fungal species can produce mycotoxins in drycured meats, such as aflatoxins
      and ochratoxins, which, when ingested, can produce carcinogenic and mutagenic
      effects in humans. Contamination of these products can occur at different points
      of the production chain, from the field (animal contaminated with feed) to the
      production or storage of the final product. Although the presence of mycotoxins
      in drycured meats has been reported in several regions of the world, the presence
      of these contaminants are not legislated in most countries. Therefore, it is
      important to put in place methods to identify and reduce the contamination of dry
      cured meats, minimizing the consumption and deleterious effects caused by
      mycotoxins. This review aimed to describe mycotoxin-producing fungi, mycotoxins,
      the relationship between human food and animal feed; legislation; incidence,
      identification and control methods for mycotoxins in dry-cured meats intended for
      human consumption.

PMID- 29217268
TI  - Novel in vitro and in silico insights of the multi-biological activities and
      chemical composition of Bidens tripartita L.
AB  - Bidens tripartita L. is a traditional phyto-remedy used in several countries, yet
      there is still a paucity of data on its biological potential. We aimed to provide
      new insights on the pharmacological potential of extracts prepared from B.
      tripartita via highlighting its antioxidant, key enzymes inhibitory potency, and
      DNA protecting effects. Phytochemical profile was established using High
      Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) and
      bioactive compound(s) docked against target enzymes using in silico methods.
      Cytotoxicity against three cancer cell lines was assessed using the
      methylthiazolyldiphenyl-tetrazolium bromide (MTT) cell viability test. The main
      compounds were luteolin-7-glucoside (cynaroside), chlorogenic acid, and
      epicatechin in the extracts. The methanol extract exhibited the highest radical
      scavenging activity. Ethyl acetate extract showed strongest alpha-amylase
      inhibitory activity, while the best alpha-glucosidase inhibitory effect recorded
      for the methanol extract. Molecular docking showed that cynaroside strongly
      interact to alpha-glucosidase cavity by establishing six hydrogen bonds. B.
      tripartita extracts were found to protect supercoiled form of pUC19 plasmid
      (>70%) and also showed anti-proliferative properties. Results amassed in the
      present study add on to a growing body of literature on the multi-pharmacological
      potency of B. tripartita which can be applied to bio-products development geared
      towards management of common diseases.

PMID- 29217269
TI  - Bacterial and fungal composition profiling of microbial based cleaning products.
AB  - Microbial based cleaning products (MBCPs) are a new generation of cleaning
      products that are gaining greater use in household, institutional, and industrial
      settings. Little is known about the exact microbial composition of these products
      because they are not identified in detail on product labels and formulations are
      often proprietary. To gain a better understanding of their microbial and fungal
      composition towards risk assessment, the cultivable microorganisms and rDNA was
      surveyed for microbial content in five different MBCPs manufactured and sold in
      North America. Individual bacterial and fungal colonies were identified by
      ribosequencing and fatty acid methyl ester (FAME) gas chromatography. Metagenomic
      DNA (mDNA) corresponding to each of the products was subjected to amplification
      and short read sequencing of seven of the variable regions of the bacterial 16S
      ribosomal DNA. Taken together, the cultivable microorganism and rDNA survey
      analyses showed that three of the products were simple mixtures of Bacillus
      species. The two other products featured a mixture of cultivable fungi with
      Bacilli, and by rDNA survey analysis, they featured greater microbial complexity.
      This study improves our understanding of the microbial composition of several
      MBCPs towards a more comprehensive risk assessment.

PMID- 29217270
TI  - Kafirin from Sorghum bicolor inhibition of inflammation in THP-1 human
      macrophages is associated with reduction of intracellular reactive oxygen
      species.
AB  - Aberrant inflammation as a result of activation of the transmembrane protein Toll
      like receptor 4 belonging to pattern recognition receptor and subsequent
      phosphorylation of signaling proteins facilitated by reactive oxygen species has
      been linked to a myriad of diseases. Sorghum is a drought-resistant cereal with
      health promoting properties associated with its biologically active substances
      such as kafirin. Kafirin is an alcohol soluble protein and accounts for as much
      as 70% of the total proteins in sorghum. The objective was to determine the
      effect of kafirin on lipopolysaccharide (LPS)-induced inflammation in THP-1 human
      macrophages. THP-1 human monocytic leukemia cells were differentiated into
      macrophages by phorbol-12-myristate 13-acetate followed by treatment of LPS with
      or without 50 MUg/mL or 100 MUg/mL concentrations of kafirin. Kafirin at 100
      MUg/mL reduced the production of pro-inflammatory cytokines IL-1beta, IL-6 and
      TNF-alpha by 28.3%, 74.0%, and 81.4%, respectively. Kafirin reduced production of
      intracellular reactive oxygen species is associated with reduced phosphorylation
      of extracellular regulated kinase1/2 and c-JUN N-terminal kinase and nuclear
      translocation of p65 and c-JUN transcription factors. Our results showed for the
      first time the anti-inflammatory property of kafirin purified from sorghum in LPS
      induced THP-1 human macrophages.

PMID- 29217271
TI  - Truck safety evaluation on Wyoming mountain passes.
AB  - The Manual on Uniform Traffic Control Devices (MUTCD) for Streets and Highways
      recommends hill signs be placed in advance of downgrade descent of mountain
      passes. Mountain passes increase the risk of a runaway, or out of control trucks
      and so the advance warning signs inform the driver to take special precautions
      such as reducing speed or using lower gears during the descent. The Wyoming
      Department of Transportation has installed steep grade advance warning systems on
      Wyoming mountain passes. However, concerns for out of control trucks on the
      mountain passes persist. The objective of this study is to evaluate the safety
      effectiveness of steep grade advance warning signs for trucks on Wyoming mountain
      passes. The safety evaluation was carried out by implementing a zero-inflated
      negative binomial modeling technique for predicting truck crashes on mountain
      passes. The outcome was two models that showed the risk of runaway truck
      accidents were high at locations where either the grades were steep and long or
      the grades were long with multiple vertical curves. The analysis showed the
      current advance warning systems were not significantly impacting truck crash
      risks at the high risk locations. The study, therefore, recommends some
      improvements to the current advanced warning signs or implementing an improved
      Federal Highway Administration Grade Severity Rating System based warning system
      that will significantly improve truck safety at the hazardous locations. The
      study informs policy makers on the safety issues on Wyoming Mountain passes with
      regards to runaway trucks and makes recommendations for reducing the risk of
      runaway truck crashes on mountain passes.

PMID- 29217272
TI  - Inhibition of hepatitis B virus gene expression: A step towards functional cure.

PMID- 29217274
TI  - Contact wear of artificial denture teeth.
AB  - PURPOSE: High wear resistance of denture teeth preserves good occlusal
      relationship and sufficient parafunctional stability. This in-vitro investigation
      aimed to determine and compare the wear performance of different artificial
      denture teeth. METHODS: Denture teeth of fifteen commercial products (n=8/group)
      were loaded in a pin-on-block design using steatite antagonists (d=3mm). Cyclic
      loading (50 N) was applied for 120,000 loadings (f=1.2Hz) with simultaneous
      thermal cycling (distilled water, 5 degrees C/55 degrees C, 2min/cycle). A
      loading cycle consisted of a vertical 1mm impact and a subsequent lateral 1mm
      sliding movement. Worn areas were digitalized (3-D-laser-scanning-microscope).
      Maximum and mean wear depth and surface roughness were determined and
      statistically compared (one-way Anova, Tukey-HSD test, alpha=0.05). Worn surfaces
      and cut specimens were investigated with scanning electron microscopy (SEM).
      RESULTS: Maximum wear varied between 475.1MUm and 1232.2MUm. Mean wear was
      between 241.1MUm and 753.6MUm with significant differences (p<0.001) between
      individual materials. Mean and maximum wear showed a significant correlation
      (Pearson's correlation coefficient: 0.942). Surface roughness increased between
      unworn to worn surface by 1.2MUm (Ra, p=0.387) and by 41.7MUm (Rz, p=0.000). All
      materials provided round or drop-shaped wear traces. Superficial analysis showed
      no cracks, chipping or fractures in the worn areas. Detailed evaluation of cut
      specimens with SEM exposed cracks on the bottom of the wear traces. CONCLUSIONS:
      Denture teeth showed significantly different in-vitro wear performance and
      increased roughness in the wear trace. Differences may be attributed to the
      composition of the materials, regarding both filler and polymer structure. The
      selection of teeth might contribute to enhanced in-vivo performance of the
      denture.

PMID- 29217275
TI  - Mechanistic understanding of ragweed pollen for oral vaccine delivery.

PMID- 29217273
TI  - LTBPs in biology and medicine: LTBP diseases.
AB  - The latent transforming growth factor (TGF) beta binding proteins (LTBP) are
      crucial mediators of TGFbeta function, as they control growth factor secretion,
      matrix deposition, presentation and activation. Deficiencies in specific LTBP
      isoforms yield discrete phenotypes representing defects in bone, lung and
      cardiovascular development mediated by loss of TGFbeta signaling. Additional
      phenotypes represent loss of unique TGFbeta-independent features of LTBP effects
      on elastogenesis and microfibril assembly. Thus, the LTBPs act as sensors for the
      regulation of both growth factor activity and matrix function.

PMID- 29217276
TI  - Editorial.

PMID- 29217277
TI  - Absence of hybridization with the wild-type and mutant rpoB probes in the
      Genotype MTBDRplus assay detects 'disputed' rifampicin mutations.
AB  - OBJECTIVE: Mycobacterium tuberculosis isolates that fail to hybridize to at least
      one rpoB wild-type or any mutation probe on the Genotype MTBDRplus strip are
      assumed to be rifampicin-resistant. However, the precise mutation(s) are unknown.
      We sought to identify the mutations in isolates with such hybridization patterns
      and determine if the mutations are associated with resistance to rifampicin.
      METHODS: In this study, 275 M. tuberculosis isolates were screened with the
      Genotype MTBDRplus assay to identify isolates with the hybridization pattern.
      These isolates were sequenced and their minimum inhibitory concentrations (MIC)
      determined using the Bactec MGIT 960 system. RESULTS: Among the 275 isolates
      tested, 15 (6%) isolates with the hybridization pattern were identified.
      Sequencing showed that failure to hybridize to rpoB wild-type probes resulted
      from the presence of 'disputed' rifampicin mutations, which are mutations not
      always associated with a rifampicin-resistant phenotype. All, except 3/15,
      isolates had a rifampicin-resistant phenotype (MIC > 1 MUg/mL). One of the three
      isolates with a rifampicin-susceptible phenotype had the same mutation at
      position 526 (His526Leu) as another isolate that had a rifampicin-resistant
      phenotype. CONCLUSION: The recommendation of the Genotype MTBDRplus assay to
      assume rifampicin resistance based solely on failure to hybridize to rpoB wild
      type probe allows the identification of important RIF-resistant isolates. About
      20% (3/15) of such isolates could be missed by relying only on the standard MGIT
      960 DST assay for drug susceptibility testing.

PMID- 29217278
TI  - Colistin exposure as a risk factor for infections caused by inherently colistin
      resistant Enterobacteriaceae-a case-control study.
AB  - OBJECTIVES: Epidemiological studies have suggested an association between
      increased colistin use and selection for inherently colistin-resistant
      Enterobacteriaceae (ICRE). We aimed to evaluate whether colistin exposure is a
      risk factor for ICRE infection. METHODS: A matched 1:1 case-control study
      including patients recently hospitalized for >=14 days with ICRE infection as
      cases matched with similar patients with a clinical isolate of a colistin
      susceptible Enterobacteriaceae as controls was performed. Univariate analysis
      using McNemar test and multivariate analysis were conducted to explore risk
      factors for ICRE isolation, including colistin exposure 90 days before the
      positive culture. RESULTS: We included 446 patients, 223 cases and 223 controls
      matched for gender, age, department, year, source of culture and duration of
      hospitalization before positive culture. Colistin exposure was significantly
      associated with ICRE isolation in both univariate (14/223, 6.3% of cases versus
      4/223, 1.8% of controls, p 0.031) and multivariate analyses (odds ratio 4.415,
      95% CI 1.078-18.082). Curtailed functional capacity was a significant risk factor
      for ICRE as well. Exposure to other broad-spectrum antibiotics was associated
      with isolation of a colistin-susceptible pathogen. CONCLUSIONS: Exposure to
      colistin is associated with an increased risk of isolating an inherently colistin
      resistant Enterobacteriaceae in patients with prolonged hospitalization. This
      should be taken into account while considering empirical therapy for such
      patients. Use of colistin should be judicious. The correlation between duration
      and magnitude of exposure and ICRE infection should be investigated in further
      studies.

PMID- 29217279
TI  - Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins
      for cell entry.
AB  - Human coronaviruses (HCoVs) enter cells via two distinct pathways: the endosomal
      pathway using cathepsins to activate spike protein and the cell-surface or early
      endosome pathway using extracellular proteases such as transmembrane protease
      serine 2 (TMPRSS2). We previously reported that clinical isolates of HCoV-229E
      preferred cell-surface TMPRSS2 to endosomal cathepsin for cell entry, and that
      they acquired the ability to use cathepsin L by repeated passage in cultured
      cells and were then able to enter cells via the endosomal pathway. Here, we show
      that clinical isolates of HCoV-OC43 and -HKU1 preferred the cell-surface TMRRSS2
      to endosomal cathepsins for cell entry, similar to HCoV-229E. In addition, the
      cell-culture-adapted HCoV-OC43 lost the ability to infect and replicate in air
      liquid interface cultures of human bronchial tracheal epithelial cells. These
      results suggest that circulating HCoVs in the field generally use cell-surface
      TMPRSS2 for cell entry, not endosomal cathepsins, in human airway epithelial
      cells.

PMID- 29217280
TI  - Photosome membranes merge and organize tending towards rhombohedral symmetry when
      light is emitted.
AB  - Polynoid worm elytra emit light when mechanically or electrically stimulated.
      Specialized cells, the photocytes, contain light emitting machineries, the
      photosomes. Successive stimulations induce light intensity variations and show a
      coupling within and between photosomes. Here, we describe, using electron
      tomography of cryo-substituted elytra and freeze-fracturing, the structural
      transition associated to light emission: undulating tubules come closer, organize
      and their number forming photosomes increases. Two repeating undulating tubules
      in opposite phase compose the photosome. Undulations are located on three
      hexagonal layers that regularly repeat and are equally displaced, in x y and z.
      The tubule membranes within layers merge giving rise to rings that tend to obey
      to quasi-rhombohedral symmetry. Merging may result either from close-association,
      hemifusion (one leaflet fusion) or from fusion (two leaflets fusion). Although
      the resolution of tomograms is not sufficient to distinguish these three cases,
      freeze-fracturing shows that hemifusion is a frequent process that leads to an
      reversible anastomosed membrane complex favoring communications, appearing as a
      major coupling factor of photosome light emission.

PMID- 29217281
TI  - Risk scores for outpatient management of febrile neutropenia: Is the MASCC
      slipping?

PMID- 29217282
TI  - Atypical dopamine transporter inhibitors attenuate compulsive-like
      methamphetamine self-administration in rats.
AB  - Methamphetamine (METH) is a highly addictive drug, but no pharmacological
      treatment is yet available for METH use disorders. Similar to METH, the wake
      promoting drug (R)-modafinil (R-MOD) binds to the dopamine transporter (DAT).
      Unlike METH, R-MOD is not a substrate for transport by DAT and has low abuse
      potential. We tested the hypothesis that the atypical DAT inhibitor R-MOD and
      compounds that are derived from modafinil would decrease METH intake by reducing
      the actions of METH at the DAT. We tested the effects of systemic injections of R
      MOD and four novel modafinil-derived ligands with increased DAT affinity (JJC8
      016, JJC8-088, JJC8-089, and JJC8-091) on intravenous (i.v.) METH self
      administration in rats that were allowed short access (ShA; 1 h) or long access
      (LgA; 6 h) to the drug. ShA rats exhibited stable METH intake over sessions,
      whereas LgA rats exhibited an escalation of drug intake. R-MOD decreased METH
      self-administration in ShA and LgA rats (in the 1st hour only). JJC8-091 and JJC8
      016 decreased METH self-administration in both ShA and LgA rats. JJC8-089
      decreased METH self-administration in LgA rats only, whereas JJC8-088 had no
      effect on METH self-administration in either ShA or LgA rats. These findings
      support the potential of atypical DAT inhibitors for the treatment of METH use
      disorders and suggest several novel compounds as candidate drugs.

PMID- 29217284
TI  - Cost variation and opportunities for cost reduction for laparoscopic
      cholecystectomy.
AB  - BACKGROUND: We performed 163 laparoscopic cholecystectomies at our institution
      during the third quarter of 2016. Direct supply cost per case varied from $524 to
      $1,022 among 14 surgeons. The purpose of this study was to determine the reasons
      for cost variation between high- and low-cost surgeons and identify opportunities
      for cost reduction. METHODS: Average cost of supplies per case was examined for
      laparoscopic cholecystectomy during a 6-month period. Two groups were created,
      with the 4 highest-cost surgeons comprising group A and the 2 lowest-cost
      surgeons comprising group B. The cost for each item was identified, and
      utilization was compared between groups. RESULTS: The average supply cost per
      case in group A was significantly greater than group B ($930 vs. $518). The
      difference persisted in subgroup analyses of both inpatients and patients with
      high American Society of Anesthesiologists scores. Compared with group A,
      surgeons in group B used reusable instruments more often and tended to choose
      lower-cost disposables. CONCLUSIONS: Significant variation in direct cost exists
      between surgeons performing laparoscopic cholecystectomy. Much of the cost
      difference can be accounted for by a relatively small number of high-cost
      instruments. We identified areas for cost savings by substituting lesser cost
      alternatives without compromising the quality of patient care.

PMID- 29217283
TI  - Insulin-mediated synaptic plasticity in the CNS: Anatomical, functional and
      temporal contexts.
AB  - For decades the brain was erroneously considered an insulin insensitive organ.
      Although gaps in our knowledge base remain, conceptual frameworks are starting to
      emerge to provide insight into the mechanisms through which insulin facilitates
      critical brain functions like metabolism, cognition, and motivated behaviors.
      These diverse physiological and behavioral activities highlight the region
      specific activities of insulin in the CNS; that is, there is an anatomical
      context to the activities of insulin in the CNS. Similarly, there is also a
      temporal context to the activities of insulin in the CNS. Indeed, brain insulin
      receptor activity can be conceptualized as a continuum in which insulin promotes
      neuroplasticity from development into adulthood where it is an integral part of
      healthy brain function. Unfortunately, brain insulin resistance likely
      contributes to neuroplasticity deficits in obesity and type 2 diabetes mellitus
      (T2DM). This neuroplasticity continuum can be conceptualized by the mechanisms
      through which insulin promotes cognitive function through its actions in brain
      regions like the hippocampus, as well as the ability of insulin to modulate
      motivated behaviors through actions in brain regions like the nucleus accumbens
      and the ventral tegmental area. Thus, the goals of this review are to highlight
      these anatomical, temporal, and functional contexts of insulin activity in these
      brain regions, and to identify potentially critical time points along this
      continuum where the transition from enhancement of neuroplasticity to impairment
      may take place. This article is part of the Special Issue entitled 'Metabolic
      Impairment as Risk Factors for Neurodegenerative Disorders.'

PMID- 29217285
TI  - Outcomes and palliative care utilization in patients with dementia and acute
      abdominal emergency: opportunities for surgical quality improvement.
AB  - BACKGROUND: When patients with dementia develop acute surgical abdomen, patients,
      surrogates, and surgeons need accurate prognostic information to facilitate goal
      concordant decision making. Palliative care can assist with communication,
      symptom management, and family and caregiver support in this population. We aimed
      to characterize outcomes and patterns of palliative care utilization among
      patients with dementia, presenting with abdominal surgical emergency. METHOD: We
      retrospectively queried the National Inpatient Sample for patients aged >50 years
      with dementia and acute abdominal emergency who were admitted nonelectively 2009
      2013, utilizing ICD-9-CM codes for dementia and surgical indication. We
      characterized outcomes and identified predictors of palliative care utilization.
      RESULTS: Among 15,209 patients, in-hospital mortality was 10.2%, the nonroutine
      discharge rate was 67.2%, and 7.5% received palliative care. Patients treated
      operatively were less likely to receive palliative care than those who did not
      undergo operation (adjusted OR = 0.50; 95% CI 0.41-0.62). Only 6.4% of patients
      discharged nonroutinely received palliative care. CONCLUSION: Patients with
      dementia and acute abdominal emergency have considerable in-hospital mortality, a
      high frequency of nonroutine discharge, and low palliative care utilization. In
      this group, we discovered a large gap in palliative care utilization,
      particularly among those treated operatively and those who are discharged
      nonroutinely.

PMID- 29217287
TI  - Discussion.

PMID- 29217286
TI  - Pediatric-protocol of multimodal therapy is associated with improved survival in
      AYAs and adults with rhabdomyosarcoma.
AB  - BACKGROUND: Multimodal therapy is the standard treatment for pediatric
      rhabdomyosarcoma, but for adolescents and young adults (AYAs: ages 15-39) and
      older adults with rhabdomyosarcoma, the use of adjuvant therapy is variable, and
      survival is greatly decreased compared with younger patients. METHODS: All
      patients with rhabdomyosarcoma who had a curative operative were identified from
      the 1998-2012 National Cancer Database. Regression analyses identified
      independent factors relating to receipt of multimodal therapy (resection +
      chemotherapy + radiation) and the influence of multimodal therapy on 5-year
      overall survival. RESULTS: Of 2,312 patients, 44% were pediatric (age < 15
      years), 22% AYA (ages 15-39), and 34% adult (age >= 40 years). Adults received
      multimodal therapy least often (pediatric: 62%, AYA: 46%, adults: 24%; P < .001),
      even after controlling for demographic characteristics, tumor features, and
      stage. In the entire cohort, multimodal therapy was associated with a decreased
      risk of death within 5 years (hazard ratio [HR] 0.72, 95% confidence interval
      [CI] 0.62-0.84), with similar findings after stratification by age (pediatric: HR
      0.64, 95% CI 0.48-0.85; AYA: HR 0.72, 95% CI 0.55-0.95; adult: HR 0.74, 95% CI
      0.58-0.93). In AYAs only, black and Hispanic patients had an increased risk of
      death within 5 years (black patients: HR 1.64, 95% CI 1.14-2.37; Hispanic
      patients: HR 1.62, 95% CI 1.11-2.36). CONCLUSION: This first large national study
      suggests that multimodal therapy is independently associated with improved
      survival for both AYAs and adults with rhabdomyosarcoma, similar to pediatric
      patients, but multimodal therapy is appreciably underused. Implementation of
      multimodal therapy for all patients could potentially improve overall outcomes of
      patients with rhabdomyosarcoma.

PMID- 29217289
TI  - JAVELIN: avelumab another spear to fight urothelial carcinoma.

PMID- 29217288
TI  - Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid
      Tumor): pooled results from two expansion cohorts of an open-label, phase 1
      trial.
AB  - BACKGROUND: The approval of anti-programmed death ligand 1 (PD-L1) and anti
      programmed death 1 agents has expanded treatment options for patients with
      locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal
      anti-PD-L1 antibody, has shown promising antitumour activity and safety in this
      disease. We aimed to assess the safety profile in patients (both post-platinum
      therapy and cisplatin-naive) treated with avelumab and to assess antitumour
      activity of this drug in post-platinum patients. METHODS: In this pooled analysis
      of two cohorts from the phase 1 dose-expansion JAVELIN Solid Tumor study,
      patients aged 18 years and older with histologically or cytologically confirmed
      locally advanced or metastatic urothelial carcinoma that had progressed after at
      least one previous platinum-based chemotherapy were enrolled from 80 cancer
      treatment centres or hospitals in the USA, Europe, and Asia. Eligible patients
      had adequate end-organ function, an Eastern Cooperative Oncology Group
      performance status of 0 or 1, life expectancy of at least 3 months, and at least
      one measurable lesion. Cisplatin-ineligible patients who might have been
      previously treated in the perioperative setting, including platinum-naive
      patients, were also eligible. Patients unselected for PD-L1 expression received
      avelumab (10 mg/kg, 1 h intravenous infusion) every 2 weeks until confirmed
      disease progression, unacceptable toxicity, or other criterion for withdrawal.
      The primary endpoint for this efficacy expansion cohort was confirmed best
      overall response (according to RECIST version 1.1), adjudicated by independent
      review. Safety analysis was done in all patients who received at least one dose
      of avelumab. Antitumour activity was assessed in post-platinum patients who
      received at least one dose of avelumab. This trial is registered with
      ClinicalTrials.gov, number NCT01772004; enrolment in this cohort of patients with
      metastatic urothelial carcinoma is closed and the trial is ongoing. FINDINGS:
      Between Sept 3, 2014, and March 15, 2016, 329 patients with advanced metastatic
      urothelial carcinoma were screened for enrolment into this study; 249 patients
      were eligible and received treatment with avelumab for a median of 12 weeks (IQR
      6.0-19.7) and followed up for a median of 9.9 months (4.3-12.1). Safety and
      antitumour activity were evaluated at data cutoff on June 9, 2016. In 161 post
      platinum patients with at least 6 months of follow-up, a best overall response of
      complete or partial response was recorded in 27 patients (17%; 95% CI 11-24),
      including nine (6%) complete responses and 18 (11%) partial responses. The most
      frequent treatment-related adverse events (any grade in >=10% patients) were
      infusion-related reaction (73 [29%]; all grade 1-2) and fatigue (40 [16%]). Grade
      3 or worse treatment-related adverse events occurred in 21 (8%) of 249 patients,
      the most common of which were fatigue (four [2%]), and asthenia, elevated lipase,
      hypophosphataemia, and pneumonitis in two (1%) patients each. 19 (8%) of 249
      patients had a serious adverse event related to treatment with avelumab, and one
      treatment-related death occurred (pneumonitis). INTERPRETATION: Avelumab showed
      antitumour activity in the treatment of patients with platinum-refractory
      metastatic urothelial carcinoma; a manageable safety profile was reported in all
      avelumab-treated patients. These data provide the rationale for therapeutic use
      of avelumab in metastatic urothelial carcinoma and it has received accelerated US
      FDA approval in this setting on this basis. FUNDING: Merck KGaA, and Pfizer Inc.

PMID- 29217290
TI  - Growth patterns in early juvenile idiopathic arthritis: Results from the
      Childhood Arthritis Prospective Study (CAPS).
AB  - OBJECTIVES: To investigate early vertical growth patterns and factors associated
      with poor growth in a modern inception cohort of UK children with juvenile
      idiopathic arthritis (JIA) using data from the Childhood Arthritis Prospective
      Study (CAPS). METHODS: A study period of 3 years was chosen. Children included in
      this analysis had a physician diagnosis of JIA and had height measurements
      available at both baseline and at 3-years of follow-up. Height is presented as z
      scores calculated using World Health Organisation growth standards for age and
      gender. Growth over the 3-year period was assessed using change in z-score and
      height velocity. Univariable and multivariable linear regressions were used to
      identify factors associated with height z-score at baseline and change of height
      z-score at 3 years. RESULTS: 568 patients were included; 65% female, median
      baseline age 7.4 years [interquartile range (IQR) 3.6, 11.2], median symptom
      duration at presentation 5.5 months [IQR 3.1, 11.6]. Height z-score decreased
      significantly from baseline to 3 years (p <= 0.0001); baseline median height z
      score was -0.02 (IQR -0.71, 0.61), decreasing to -0.47 (IQR -1.12, 0.24) at 3
      years. Growth restriction, defined as change of height z-score <=-0.5, was
      observed in 39% of patients. At 3 years, higher baseline height z-score was the
      strongest predictor for a negative change in height z-score [-0.3 per unit of
      baseline height z-score (95% CI: -0.36, -0.24), p < 0.0001]. CONCLUSIONS:
      Although overall height at 3 years after initial presentation to rheumatology is
      within the population norm, as a cohort, children with JIA experience a reduction
      of growth in height over the first 3 years of disease. Late presentation to
      paediatric rheumatology services is associated with lower height at presentation.
      However, patients with the lowest height z scores at presentation were also the
      most likely to see an improvement at 3 years. The impact of JIA on growth
      patterns is important to children and families and this study provides useful new
      data to support informed clinical care.

PMID- 29217291
TI  - Pregnancy outcomes in adult patients with dermatomyositis and polymyositis.
AB  - OBJECTIVE: The idiopathic inflammatory myopathies dermatomyositis (DM) and
      polymyositis (PM) are autoimmune diseases that can affect females of childbearing
      potential. We assessed pregnancy outcomes in DM and PM patients compared with the
      general obstetric population. METHODS: The Nationwide Inpatient Sample (NIS)
      (1993-2007) was used to identify delivery-associated hospitalizations in women
      with DM or PM (DM/PM, n = 853). Controls were from the general obstetric
      population delivery-associated hospitalizations matched to each case by year of
      delivery. Pregnancy outcomes included hospital length of stay (LOS), hypertensive
      disorders (HTN), premature rupture of membranes (PROM), intrauterine growth
      restriction (IUGR), and cesarean delivery. Multivariate regression analyses were
      performed using maternal age, race/ethnicity, and diabetes mellitus as
      covariates. RESULTS: On multivariate analysis, patients with DM/PM had longer LOS
      compared to controls (p < 0.001). DM/PM was associated with an increased risk of
      hypertensive disorders compared to controls (OR = 2.90, 95% CI: 2.00-4.22). There
      were no differences in rates of PROM, IUGR, or cesarean section in patients with
      DM/PM compared with controls. Independent of a DM/PM diagnosis, African-American
      race, older age, and diagnosis of diabetes increased the hospital LOS (p <
      0.001). African-American race and diabetes increased the risk of hypertensive
      disorders (OR = 1.38, 95% CI: 1.19-1.60; OR = 2.94, 95% CI: 2.04-4.23,
      respectively) compared to controls. CONCLUSION: These data suggest that patients
      with inflammatory myopathies are at increased risk of hypertensive disorders of
      pregnancy and longer length of hospitalization. Vigilant monitoring of blood
      pressure is advisable in pregnant patients with DM or PM.

PMID- 29217292
TI  - Functional incapacity related to rotator cuff syndrome in workers. Is it
      influenced by social characteristics and medical management?
AB  - STUDY DESIGN: Survey. INTRODUCTION: Rotator cuff syndrome (RCS) is one of the
      most common musculoskeletal disorders reported in workers. The functional
      incapacity related to RCS may vary according to the sociodemographic context and
      to the medical management. PURPOSE OF THE STUDY: The purpose of this is to
      analyze the RCS-related functional incapacity assessed by the Disabilities of the
      Arm, Shoulder and Hand (DASH) questionnaires in workers according to their
      sociodemographic characteristics and the use of care. METHODS: A cross-sectional
      study was carried out on a French sample of workers diagnosed with RCS. The DASH
      and DASH-work scores were studied according to the sociodemographic factors,
      musculoskeletal symptoms, and RCS medical management during the preceding 12
      months. RESULTS: Two hundred seven workers who suffered from RCS filled out the
      questionnaire of which 80% were still working. The DASH score was significantly
      higher in women (24.0 vs 17.4; P < .01; effect size (d) = 0.39), in patients over
      the age of 50 years (23.6 vs 11.3; P < .005) and in case of another upper limb
      musculoskeletal disorder (P < .0001; d >= 0.4). The DASH and DASH-work scores
      were significantly higher in case of use of care for RCS (P < .005; d > 0.6).
      DISCUSSION: The demographic factors and the RCS medical management influenced the
      overall incapacity assessed by the DASH questionnaire. Work incapacity was more
      especially related to the use of care for RCS. CONCLUSION: The sociodemographic
      and medical parameters added to other established predictors could help guide
      clinicians in managing their patients.

PMID- 29217293
TI  - An evaluation of two types of exercise classes, containing shoulder exercises or
      a combination of shoulder and thoracic exercises, for the treatment of
      nonspecific shoulder pain: A case series.
AB  - STUDY DESIGN: A case series was carried out. INTRODUCTION: There is a lack of
      evidence exploring the effectiveness of group exercise classes for people with
      nonspecific shoulder pain (NSSP). Also, there is a lack of research that measures
      potential reductions in thoracic kyphosis after exercise interventions in people
      with NSSP. PURPOSE OF THE STUDY: To observe changes in shoulder pain, disability,
      and thoracic kyphosis in 2 groups of people with NSSP, after 2 different types of
      group exercise classes. METHODS: People with NSSP received a 6-week block of
      exercises classes containing either shoulder exercises alone (shoulder group, n =
      20) or a mixture of shoulder and thoracic extension exercises (thoracic group, n
      = 19). The Disabilities of the Arm, Shoulder and Hand questionnaire for
      disability and the Numeric Rating Scale for pain were measured at baseline, 6
      weeks, and 6 months. Thoracic kyphosis was measured at baseline and 6 weeks using
      the manual inclinometer. RESULTS: Significant and clinically meaningful
      improvements in Numeric Rating Scale and Disabilities of the Arm, Shoulder and
      Hand were demonstrated in both groups at 6-week and 6-month follow-up (P < .001).
      Effect sizes ranged from 0.78-1.16 in the shoulder group and 0.85-1.88 in the
      thoracic group. Thoracic kyphosis did not change beyond measurement error in
      either group. DISCUSSION/CONCLUSION: Group exercise classes can improve shoulder
      pain and disability in people with NSSP. Resting thoracic kyphosis did not change
      after either exercise intervention, which suggests that the treatment effect was
      not due to a change in static thoracic spine posture.

PMID- 29217294
TI  - The use of aripiprazole for tic disorders in children and adolescents and
      implications for resource limited settings in the developing world.

PMID- 29217295
TI  - Investigation of a minor groove-binding polyamide targeted to E2F1 transcription
      factor in chronic myeloid leukaemia (CML) cells.

PMID- 29217298
TI  - Carbonylated proteins contribute to the darkness around facial pores.

PMID- 29217299
TI  - High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory
      dendritic cells generated for clinical testing in organ transplantation.
AB  - Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead
      purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They
      exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively
      high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10
      production compared to control immature DC (iDC). Following Toll-like receptor 4
      ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation
      and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC
      (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10,
      the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naive
      and memory allogeneic CD4+ and CD8+ T cell proliferation and IFNgamma, IL-17A and
      perforin/granzyme B production in MLR. Their stimulatory function was enhanced
      however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR)
      sequencing revealed that, among circulating T cell subsets, memory CD8+ T cells
      contained the most alloreactive TCR clonotypes and that, while matDC expanded
      these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated
      responses. These findings demonstrate the feasibility of generating highly
      purified GMP-grade DCreg for systemic infusion, their influence on the
      alloreactive T cell response, and a key mechanistic role of the PD1 pathway.

PMID- 29217297
TI  - Defects in Bioenergetic Coupling in Schizophrenia.
AB  - Synaptic neurotransmission relies on maintenance of the synapse and meeting the
      energy demands of neurons. Defects in excitatory and inhibitory synapses have
      been implicated in schizophrenia, likely contributing to positive and negative
      symptoms as well as impaired cognition. Recently, accumulating evidence has
      suggested that bioenergetic systems, important in both synaptic function and
      cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal
      models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as
      well as bioenergetic abnormalities. We report findings on the bioenergetic
      interplay of astrocytes and neurons and discuss how dysregulation of these
      pathways may contribute to the pathogenesis of schizophrenia, highlighting
      metabolic systems as important therapeutic targets.

PMID- 29217296
TI  - Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA
      PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder
      Consortia.
AB  - BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in
      posttraumatic stress disorder (PTSD), but findings have not always been
      consistent. Here, we present the results of a large-scale neuroimaging consortium
      study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing
      Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS:
      We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients)
      contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to
      date. We assessed the volumes of eight subcortical structures (nucleus accumbens,
      amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral
      ventricle). We used a standardized image-analysis and quality-control pipeline
      established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples,
      we found significantly smaller hippocampi in subjects with current PTSD compared
      with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller
      amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a
      significance level that was Bonferroni corrected for multiple subcortical region
      comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of
      meta-analyses of published data, and it represents an important milestone in an
      ongoing collaborative effort to examine the neurobiological underpinnings of PTSD
      and the brain's response to trauma.

PMID- 29217300
TI  - Dynamic magnetic resonance imaging of the breast: Comparison of gadobutrol vs. Gd
      DTPA.
AB  - OBJECTIVE: To compare the pharmacokinetic profile of gadobutrol versus Gd-DTPA in
      dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer. Secondary
      objectives included comparing the safety profiles and diagnostic efficacy of the
      two contrast agents for detecting additional malignant lesions. MATERIAL AND
      METHODS: This retrospective observational study included 400 patients with
      histologically confirmed breast cancer; 200 underwent DCE-MRI with Gd-DTPA
      (Magnevist(r)) and 200 underwent DCE-MRI with gadobutrol (Gadovist(r)).
      Pharmacokinetic parameters and signal intensity were analyzed in a region of
      interest placed in the area within the lesion that had greatest signal intensity
      in postcontrast sequences. We compared the two groups on pharmacokinetic
      variables (Ktrans, Kep, and Ve), time-signal intensity curves, and the number of
      additional malignant lesions detected. RESULTS: The relative signal intensity
      (enhancement) was higher with gadobutrol than with Gd-DTPA. Washout was lower
      with gadobutrol than with Gd-DTPA (46% vs. 58,29%, respectively; p=0,0323).
      Values for Ktrans and Kep were higher for gadobutrol (p=0,001). There were no
      differences in the number of histologically confirmed additional malignant
      lesions detected (p=0,387). CONCLUSIONS: Relative enhancement is greater with
      gadobutrol, but washout is more pronounced with Gd-DTPA. The number of additional
      malignant lesions detected did not differ between the two contrast agents. Both
      contrasts are safe.

PMID- 29217301
TI  - [Gut microbiota: What impact on colorectal carcinogenesis and treatment?]
AB  - The gut microbiota, composed of 1014 microorganisms, is now considered as a
      "hidden organ", regarding to its digestive, metabolic and immune functions, which
      are helpful to its host. For the last 15 years, advances in molecular biology
      have highlighted the association of gut microbiota dysbiosis with several
      diseases, including colorectal cancer. An increased abundance of some bacteria
      (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is
      associated with cancer, whereas others seem to be protective (Faecalibacterium
      prausnitzii). Several mechanisms, which are species-specific, are involved in
      colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro
      inflammatory processes and in activation of angiogenesis and cellular
      proliferation pathways. The identification of these bacteria leads to envisage
      the gut microbiota as potential screening tool for colorectal cancer. Recent
      studies showed a relation between the gut microbiota and the efficacy and
      toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies
      (including ipilimumab). Therapeutic approaches targeting the gut microbiota are
      now available (probiotics, fecal microbiota transplantation...). New therapeutic
      strategy combining both chemotherapy and/or immunotherapy with an adjuvant
      treatment targeting the gut microbiota can now be developed in order to improve
      treatment response and tolerance.

PMID- 29217302
TI  - C-source metabolic profilings of foodborne Shiga-toxin producing E. coli match
      serogroup differentiations and highlight functional adaptations.
AB  - The tropism of pathogenic STEC for foodstuffs and cattle reservoir is related to
      functional specializations. An investigation of C-source utilization patterns
      among and between STEC serogroups was performed using omnilog phenotypic
      microarrays (OM). OM functional groupings were compared with STEC phylogroups,
      seropathotypes, EFSA's molecular risk assessment groups and serogroups. OM INT
      reduction activities of 37 STEC strains growing on 190 C-substrates were
      compared. Each strain had its own specific C-utilization profile but 23% of the
      substrates was used by all strains, 47% by none, and 30% was variably
      metabolized. Galactose, mannose, N-acetyl-glucosamine (GlcNAc), and N-acetyl
      neuraminic acid (Neu5Ac) found in the mucus layer of the bovine small intestine
      were metabolized by all strains. The 56 most informative substrates divided the C
      utilization patterns (CP) into three clusters with: (A) harboring all O157 and
      O145 strains; (B) all O26 strains, and (C) strains of the other serogroups.
      Significant correlations between INT reduction values of pair of strains per CP
      group supported these differentiations. CP of group A and B strains were
      respectively defective in the use of galactonic acid-gamma-lactone and rhamnose.
      Most CP group C strains grew with l-lyxose. Adjusted Wallace coefficients
      analyses of the datasets indicated high probabilities for the prediction of the
      use of glycolic acid, beta-hydroxybutyric acid, l-lyxose and d-galactonic acid
      gamma-lactone and 5-keto-d-gluconic acid by a serogroup. The use of a C-substrate
      could be predicted from the classification of a strain into a phylogroup or
      seropathotype. Significantly lower numbers of C-substrates were used by
      seropathotype A strains like O157 ones. Improvements of STEC identification keys
      were proposed using the most discriminant C-substrates found in this study.

PMID- 29217303
TI  - Castleman Disease and Rosai-Dorfman Disease.
AB  - This chapter describes the main features of two different diseases, Castleman
      Disease (CD) and Rosai-Dorfman Disease (RDD). Castleman disease (CD) is a
      clinical and histopathologically heterogeneous lymphoproliferative disorder that
      encompasses at least three distinct entities with some common overlapping
      morphological features: Hyaline Vascular CD (HVCD), Unicentric Plasma Cell CD and
      Multicentric CD. The most important feature of HVCD is the presence of abnormal
      germinal centers with hyaline-vascular transformation, sometimes showing multiple
      germinal centers within a single reactive lymphoid follicle, this outlining HVCD
      as a disorder of follicular dendritic cells. Unicentric and multicentric CD are,
      in contrast, lymphoproliferative lesions. Proinflammatory hypercytokinemia is an
      essential feature of multicentric CD, distinguished by a florid clinical
      presentation. Rosai-Dorfmann Disease is a histiocytic proliferative disorder
      diagnosed by the presence of tissue infiltration by S100-positive CD1a-negative
      histiocytes and plasma cell aggregates, often with Russell bodies. A typical,
      though not specific, characteristic of the disease is emperipolesis. Initially
      considered to be an inflammatory/reactive condition, molecular studies suggest
      that at least some cases of RDD could be considered as a low-grade histiocytic
      neoplastic process.

PMID- 29217304
TI  - Warming of Irrigation Fluids for Prevention of Perioperative Hypothermia During
      Arthroscopy: A Systematic Review and Meta-analysis.
AB  - PURPOSE: To determine whether warming of irrigation fluids (32 degrees C-40
      degrees C) compared with using room-temperature irrigation fluids (20 degrees C
      22 degrees C) decreases the risk of perioperative hypothermia (<36 degrees C) for
      patients undergoing shoulder, hip, or knee arthroscopy. METHODS: One reviewer,
      with the assistance of a medical librarian, searched the following databases:
      PubMed, Embase, Cochrane Central, SPORTDiscus, Web of Science, and CINAHL
      (Cumulative Index to Nursing and Allied Health Literature). Level I and II
      studies involving shoulder, hip, or knee arthroscopy were included. Two reviewers
      screened the abstracts and titles. Two reviewers assessed the risk of bias of
      selected studies using The Cochrane Collaboration tool. Meta-analyses were
      conducted on the following outcomes: hypothermia, lowest temperature, maximum
      temperature drop, and shivering. RESULTS: Seven studies of patients undergoing
      arthroscopy were included in the qualitative synthesis (5 shoulder studies, 1 hip
      study, and 1 knee study; 501 patients). The study involving knee arthroscopy was
      excluded from the meta-analyses because of insufficient data and high clinical
      heterogeneity (surgical site distal to the core, not involving extravasation of
      large amounts of fluid). The remaining 6 studies were included in 1 or more meta
      analyses: hypothermia (5 shoulder and 1 hip study), lowest temperature (3
      shoulder and 1 hip study), maximum temperature drop (2 shoulder and 1 hip study),
      and shivering (5 shoulder and 1 hip study). Warming of irrigation fluids for
      shoulder or hip arthroscopy significantly decreased the risk of hypothermia (odds
      ratio, 0.15; 95% confidence interval [CI], 0.06-0.40; P = .0001), increased the
      lowest mean temperature (mean difference, 0.46 degrees C; 95% CI, 0.11 degrees C
      0.81 degrees C; P = .01), decreased the maximum temperature drop (mean
      difference, -0.64 degrees C; 95% CI, -0.94 degrees C to -0.35 degrees C; P <
      .0001), and decreased the risk of shivering (odds ratio, 0.25; 95% CI, 0.07-0.86;
      P = .03). CONCLUSIONS: When irrigation fluids are warmed for shoulder and hip
      arthroscopy, the risk of hypothermia is less, the drop in intraoperative
      temperature is less, the lowest body temperature is higher, and the risk of
      postoperative shivering is reduced. LEVEL OF EVIDENCE: Level II, systematic
      review of Level I and II studies.

PMID- 29217306
TI  - Improving Carboplatin Dosing Based on Estimated GFR.

PMID- 29217307
TI  - Autosomal Dominant Tubulointerstitial Kidney Disease Due to MUC1 Mutation.
AB  - Mucin 1 kidney disease, previously referred to as medullary cystic kidney disease
      type 1, is a rare hereditary kidney disease. It is one of several diseases now
      termed autosomal dominant tubulointerstitial kidney disease, as proposed by a
      KDIGO (Kidney Disease: Improving Global Outcomes) consensus report in 2014.
      Autosomal dominant tubulointerstitial kidney diseases share common clinical
      findings, such as autosomal dominant inheritance, bland urinary sediment, absent
      to mild proteinuria, and progressive loss of kidney function. Although the
      pathophysiology of mucin 1 kidney disease is still under investigation, genetic
      testing has been developed to detect the most well-known mutation, a single
      cytosine insertion into a string of 7 cytosines in the variable-number tandem
      repeat (VNTR) region of the MUC-1 gene. With this diagnostic tool, nephrologists
      can offer genetic counseling to affected families and monitor closely for
      progression of disease. We report a Hispanic patient with a strong family history
      of chronic kidney disease who tested positive for the MUC1 mutation.

PMID- 29217305
TI  - Longitudinal Weight Change During CKD Progression and Its Association With
      Subsequent Mortality.
AB  - BACKGROUND: Few studies have investigated the changes in weight that may occur
      over time among adults with the progression of chronic kidney disease (CKD).
      Whether such weight changes are independently associated with death after the
      onset of end-stage renal disease has also not been rigorously examined. STUDY
      DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We studied 3,933
      participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a
      longitudinal cohort of patients with CKD. We also performed similar analyses
      among 1,067 participants of the African American Study of Kidney Disease and
      Hypertension (AASK). PREDICTORS: Estimated glomerular filtration rate (eGFR) and
      weight change during CKD. OUTCOME: Weight and all-cause mortality after dialysis
      therapy initiation. RESULTS: During a median follow-up of 5.7 years in CRIC,
      weight change was not linear. Weight was stable until cystatin C-based eGFR
      (eGFRcys) decreased to <35mL/min/1.73m2; thereafter, weight declined at a mean
      rate of 1.45 kg (95% CI, 1.19-1.70) for every 10 mL/min/1.73m2 decline in
      eGFRcys. Among the 770 CRIC participants who began hemodialysis or peritoneal
      dialysis therapy during follow-up, a >5% annualized weight loss after eGFR
      decreased to <35mL/min/1.73m2 was associated with a 54% higher risk for death
      after dialysis therapy initiation (95% CI, 1.17-2.03) compared with those with
      more stable weight (annualized weight changes within 5% of baseline) in adjusted
      analysis. Similar findings were observed in the AASK. LIMITATIONS: Inclusion of
      research participants only; inability to distinguish intentional versus
      unintentional weight loss. CONCLUSIONS: Significant weight loss began relatively
      early during the course of CKD and was associated with a substantially higher
      risk for death after dialysis therapy initiation. Further studies are needed to
      determine whether interventions to optimize weight and nutritional status before
      the initiation of dialysis therapy will improve outcomes after end-stage renal
      disease.

PMID- 29217308
TI  - A Sustainable Model for Peer Review and Utility of At-a-Glance Analysis of Dose
      Volume Histogram in Radiation Oncology.

PMID- 29217309
TI  - Re: Letter to the Editor of Public Health in response to 'Provision of
      information to consumers about the calorie content of alcoholic drinks: did the
      responsibility deal pledge by alcohol retailers and producers increase the
      availability of calorie information?'

PMID- 29217310
TI  - About the connectivity of dual-scale media based on micro-structure based
      regional analysis of NMR flow propagators.
AB  - The characterisation of heterogeneous porous media at multiple length scales
      typically requires the classification of structure at some scale to allow the
      calculation of effective transport properties at a scale relevant for macroscopic
      description. While such a classification may be derived from various imaging
      methods, a shortcoming is often the simultaneous characterisation of the
      connectivity between regions representing different micro-structure. In this work
      we combine NMR based flow propagators with the simulations performed on
      corresponding reconstructed structure, and relate the NMR measurements to their
      simulated global and local representations to study fluid transport locally and
      the exchange between micro- and macro-porous regions. This is achieved by
      carrying out detailed lattice Boltzmann simulations and random walk method to
      track the displacements of tracers in each kind of region. Using Euclidean
      distance maps (EDT) we analyse the fluid invasion to regions of different scale
      and relate it to the connectivity of the system. We demonstrate that numerical
      simulation has great flexibility in providing additional sensitivity to the
      inference of region-region connectivity.

PMID- 29217311
TI  - In Pursuit of Fellowship: Results From a 2016 Survey of US Trainees.
AB  - PURPOSE: The purpose of this study was to gauge radiology trainee perceptions
      regarding the fellowship selection process and survey their perceived level of
      preparedness and desire for a fellowship-oriented lecture. METHODS: A survey,
      approved by Association of Program Coordinators in Radiology (APCR) was
      distributed via e-mail to all APCR members for distribution to their residents.
      RESULTS: A total of 98.6% (n = 261) of residents plan to pursue a fellowship. The
      most popular fellowships are interventional radiology, body, musculoskeletal, and
      Neuro. For fellowship information, residents believe that fellowship directors in
      their field of intent were the most reliable (76%), followed by fellows (65%).
      Only approximately 50% of residents felt somewhat strongly that they were
      preparing for their fellowship application correctly. Lastly, 44% of residents (n
      = 94) replied extremely likely to attend a lecture series given by fellowship
      directors, and 36% (n = 77) said somewhat likely. CONCLUSION: This survey
      demonstrates that most trainees plan to pursue fellowship training. Residents
      ranked certain resources as more important in fellowship selection, such as
      fellowship directors and fellows. Lastly, there is a high interest in a lecture
      series that would bring together fellowship directors and residents that are
      interested in that particular fellowship.

PMID- 29217312
TI  - Long-term stability of dental adhesive incorporated by boron nitride nanotubes.
AB  - OBJECTIVE: The aim of this study was to evaluate physicochemical properties, long
      term microtensile bond strength and cytotoxicity of methacrylate-based adhesive
      containing boron nitride nanotubes (BNNTs) as fillers. METHODS: A dental adhesive
      was formulated using BisGMA/HEMA, 66/33wt% (control). Inorganic BNNT fillers were
      incorporated into the adhesive at different concentrations (0.05, 0.075, 0.1 and
      0.15wt%). Analyses of degree of conversion (DC), polymerization rate [Rp.(s-1)],
      contact angle (CA) on dentin, after 24h and 6 months microtensile bond strength
      (MUTBS-24h and 6 months) were assessed. Cytotoxicity was performed through
      viability of fibroblast cells (%) by sulforhodamine B (SRB) colorimetry. RESULTS:
      DC and max. polymerization rate increased (p<0.05) after incorporating 0.075 and
      0.1wt% BNNT. The contact angle on dentin increased (p<0.05) after incorporating
      0.15wt% BNNT. The MUTBS-24h showed no changes (p>0.05) after incorporating up to
      0.15wt% BNNT comparing to control. After 6 months, MUTBS decreased (p<0.05) for
      control and 0.15wt% BNNT and BNNT groups up to 0.15wt% showed higher MUTBS than
      control (p<0.05). No difference of fibroblast growth was found among adhesives
      (p>0.05) and up to 19% of cell viability was found comparing 0.05wt% BNNT to
      positive control group (100%). SIGNIFICANCE: Incorporating boron nitride
      nanotubes up to 0.1wt% into dental adhesive increased the long-term stability to
      dentin without decreasing viability of fibroblast cell growth. Thus, the use of
      BNNTs as filler may decrease failure rate of current dentinal adhesives.

PMID- 29217313
TI  - Characteristics and Health Needs of Veterans in Jails and Prisons: What We Know
      and Do Not Know about Incarcerated Women Veterans.
AB  - PURPOSE: The majority of U.S. veterans in prisons and local jails are men, but
      incarcerated women veterans remain an important and understudied group. METHODS:
      This study reported differences in sociodemographic, health, and criminal justice
      characteristics using Veterans Affairs (VA) administrative data on a national
      sample of 30,964 incarcerated veterans (30,440 men and 524 women) who received
      outreach from the VA Health Care for Reentry Veterans program between 2007 and
      2011. Descriptive statistics and multivariable logistic regressions determined
      gender and racial differences in this population. RESULTS: Compared with
      incarcerated veterans who were men, incarcerated women veterans were younger (d =
      0.68), had significantly lower lifetime arrests (AOR, 0.65; p < .001; 99% CI,
      0.49-0.87), and were less likely to have been incarcerated for a violent offense
      (AOR, 0.47; p < .001; 99% CI, 0.35-0.63). Notably, 58% of women were of
      reproductive age. Women were more likely to have reported eye problems,
      hypertension, chronic obstructive pulmonary disease, and seizure disorder, and
      were more likely to receive a preliminary diagnosis of mood disorder than men.
      Women were more likely to have received VA benefits, used VA health care before,
      and be willing to use VA services after release. A few important differences
      emerged when stratified by race. CONCLUSIONS: These findings suggest that
      incarcerated women veterans are interested in VA health care services, but there
      is lack of information about women's health needs through the Health Care for
      Reentry Veterans program. The inclusion of Health Care for Reentry Veterans
      screening questions about women's health issues may support the VA's interests to
      better engage women veterans in care.

PMID- 29217314
TI  - Congenital Cytomegalovirus Infection and the Occurrence of Cystic Periventricular
      Leukomalacia.

PMID- 29217315
TI  - Predictors of effective therapeutic relationships between pharmacists and
      patients with type 2 diabetes: Comparison between Arabic-speaking and Caucasian
      English-speaking patients.
AB  - BACKGROUND: The benefits of pharmacist-led interventions in achieving desired
      patient outcomes have been well established. Effective patient-pharmacist
      relationships are required to provide high-quality pharmacy care. Limited
      information is available about how Arabic-speaking migrants with diabetes, in
      Australia, perceive patient-pharmacist relationship and how these perspectives
      differ from the mainstream society (represented by Caucasian English-speaking
      people). OBJECTIVE: To examine and compare the patient-pharmacist relationship,
      medication underuse and adherence levels among Arabic-speaking and Caucasian
      English-speaking patients with type 2 diabetes. METHODS: A 98-item survey
      incorporating several previously-validated measurements was completed by Arabic
      speaking migrants (ASMs) and Caucasian English-speaking patients (ESPs) with type
      2 diabetes. Participants were recruited from various healthcare settings in the
      Melbourne metropolitan area and rural Victoria, Australia. This survey-based,
      cross-sectional study was designed to explore patients' perceptions of the
      patient-pharmacist relationship. A descriptive analysis of responses was
      undertaken, and binary logistic regression was used to explore patient-pharmacist
      relationships. RESULTS: A total of 701 participants were recruited; 392 ASMs and
      309 ESPs. Of ASMs, 88.3% were non-adherent to their prescribed medication,
      compared with 45.1% of ESPs. The degree of relationship with community
      pharmacists differed significantly between ASMs and ESPs. Compared with ASMs,
      significantly more ESPs reported that they have thought about consulting a
      pharmacist when they had health problems (P = 0.002). Compared with ESPs,
      significantly fewer ASMs reported always following pharmacist recommendations
      (32% versus 61.9% respectively). CONCLUSIONS: Arabic-speaking migrants had less
      effective relationships with community pharmacists when having their
      prescriptions filled. Community pharmacists' expertise appeared to be underused.
      These minimal relationships represent missed opportunities to improve health
      outcomes.

PMID- 29217316
TI  - Prevention of Feline Injection-Site Sarcomas: Is There a Scientific Foundation
      for Vaccine Recommendations at This Time?
AB  - Recently published guidelines have made specific vaccine recommendations
      purported to potentially reduce the incidence of feline injection-site sarcomas
      (FISS). These recommendations have largely been based on experimental models of
      inflammation under different vaccine formulations. In none of these studies did
      sarcomas occur. It is scientifically untenable to address FISS risk based on
      propensity of vaccines to elicit differential inflammatory responses if none of
      those responses led to sarcoma development. Although the recommendations may
      ultimately be found to be prescient and valid, it will take considerable
      additional research before this can happen. Until then, such guidelines must be
      regarded with skepticism.

PMID- 29217317
TI  - Recent Advances in Vaccine Technologies.
AB  - This brief review discusses some recent advances in vaccine technologies with
      particular reference to their application within veterinary medicine. It
      highlights some of the key inactivated/killed approaches to vaccination,
      including natural split-product and subunit vaccines, recombinant subunit and
      protein vaccines, and peptide vaccines. It also covers live/attenuated vaccine
      strategies, including modified live marker/differentiating infected from
      vaccinated animals vaccines, live vector vaccines, and nucleic acid vaccines.

PMID- 29217318
TI  - GHRH plus arginine and arginine administration evokes the same ratio of GH
      isoforms levels in young patients with Prader-Willi syndrome.
AB  - Human GH is present in pituitary and circulation as several isoforms, the
      prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the
      preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH)
      plus arginine (ARG) administration in adult patients with Prader-Willi syndrome
      (PWS), one of the most common causes of syndromic obesity, often associated with
      GH deficiency (GHD). Aim of the present study was to measure circulating levels
      of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype
      UPD/DEL/met+: 11/11/2; age: 10.8+/-5.3years; BMI SDS: 2.0+/-2.0; GHD: 16/24;
      obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were
      analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype,
      GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured
      by a chemiluminescent or fluorescent method based on specific pairs of monoclonal
      antibodies. GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH
      but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG
      induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all
      PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the
      GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs.
      non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in
      nonobese than obese patients and in non GHD than GHD patients administered with
      either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups.
      Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after
      GHRH+ARG vs. ARG in all subgroups investigated. In conclusion, this study shows
      that administration of two different pharmacological tests, i.e. ARG, capable of
      reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts
      at pituitary level on the somatotropic cell, evokes the same ratios of GH
      isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in
      this genetic disorder does not alter the qualitative and quantitative composition
      of GH isoforms present in circulation.

PMID- 29217320
TI  - Editorial.

PMID- 29217319
TI  - Long-term analysis of surgical treatment outcomes in chronic pilonidal sinus
      disease.
AB  - BACKGROUND/PURPOSE: Chronic pilonidal sinus disease (PSD) is relatively common in
      adolescents and can be treated by various surgical techniques. This study aimed
      to evaluate the outcome in adolescents surgically treated for PSD in a single
      clinic. METHODS: PSD patients surgically treated over an 8-year period were
      retrospectively evaluated. Classical midline incision and excision with primary
      repair was performed in all. Regular follow up visits were scheduled. Evaluation
      of postoperative outpatient clinic records as well as telephone interviews for
      patients who were operated more than 6months ago were done for the long-term
      results, including coherence to regional hair care. RESULTS: There were 268
      patients with a median age of 16years; 146 (54%) were males, and 122 (46%) were
      females. Outpatient follow up records were available for 249 (92.9%) patients
      with a median of postoperative 3months (7days-49months). Moreover, 114 (42.5% of
      total) patients were interviewed by telephone 6-63 (median 25) months after the
      surgery. In 36 (13.4%) patients, wound infection or dehiscence occurred within
      the first month of surgery and was treated by secondary healing. Recurrences were
      observed in 21 (7.8%) patients all having poor local hygiene. Laser epilation was
      employed in 32 (28%) patients, and none of these had recurrences. CONCLUSIONS:
      Classical midline incision and primary closure approach for surgical treatment of
      PSD in adolescents has similar results to adults. Postoperative hair removal
      seems to reduce recurrences. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE:
      Level IV (Retrospective case series with no comparison group).

PMID- 29217321
TI  - Bronchoscopy as a screening tool for symptomatic tracheomalacia in oesophageal
      atresia.
AB  - AIM: Oesophagealatresia/tracheo-oesophageal fistula (OA-TOF) is associated with
      tracheomalacia (TM). In our institution it is routine for OA-TOF patients to
      undergo dynamic flexible bronchoscopy (DFB) assessing both the site of the
      fistula and the presence or absence of TM. We aimed to determine the value of
      this investigation as a screening tool to predict subsequent symptomatic
      tracheomalacia in these patients. METHODS: All patients with OA-TOF who underwent
      DFB at the time of initial repair between June 2014 and November 2016 were
      included prospectively. The findings at DFB were recorded. Patients were grouped
      according to the presence or absence of TM and followed to determine which of
      them developed symptomatic airway problems. The sensitivity and specificity of TM
      at initial bronchoscopy as a screening tool for subsequent symptomatic TM were
      calculated. The study was given ethical approval by our institution. MAIN
      RESULTS: Twenty-three patients were included in the study. Median follow-up was
      for 7 (1-27) months. Fifteen (65%) were found to have TM at their first DFB; 13
      (57%) subsequently developed airway symptoms, and of these 11 had TM at initial
      DFB. One patient with severe TM (>90% tracheal collapse) at initial DFB was
      completely asymptomatic following OA-TOF repair. The sensitivity was 85%, and
      specificity was 60%. The positive and negative predictive values were 73% and
      75%, respectively. CONCLUSIONS: DFB is a useful tool in many aspects of the
      management of OA/TOF. However, it is not a good screening tool to predict
      symptomatic tracheomalacia with moderate sensitivity and a low specificity. LEVEL
      OF EVIDENCE: Level IIb, Retrospective cohort study.

PMID- 29217322
TI  - Incidence of ureterovesical obstruction and Cohen antireflux surgery after
      Deflux(r) treatment for vesicoureteric reflux.
AB  - AIM: The purpose of this study was to determine the incidence of ureteric
      obstruction (UB) and requirement for Cohen antireflux surgery (CAS) after DefluxR
      treatment (DT) for vesicoureteric reflux (VUR). METHODS: Between 2011 and 2017,
      494 ureters (VUR severity <= grade III: N=291 or >grade IV: N=203) were treated
      by DT at a mean age of 4.5 (range: 0.2-24) years. Epidural Catheter Assistance
      (ECA) was used to exclude UB by injecting diluted indigo carmine solution (1-3mL)
      into an epidural catheter inserted into a ureter after DT and confirming dye flow
      within 15min. ECA+: N=181 ureters; ECA-: N=313 ureters. RESULTS: In ECA+, UB was
      detected in 5/181 (2.7%) ureters (grade II: N=1, III: N=3, and IV: N=1) treated
      by leaving the ECA catheter in situ overnight (N=4) or double J stent (DJS)
      insertion for 1month (N=2). After mean follow-up of 1.9years, one grade III DJS
      case has residual grade II VUR. In ECA-, 3/313 (0.9%) cases developed UB. One
      resolved, and one required DJS. CAS was required for 17/494 (3.4%) ureters and
      hindered by DT in 5/17 (29.4%) ureters. All are sequelae-free after mean follow
      up of 1.8years. CONCLUSIONS: UB may be more frequent than reported (3.3% versus
      0.6%-1.8%). ECA identifies potential UB. TYPE OF STUDY: Treatment study. LEVEL OF
      EVIDENCE: Level III.

PMID- 29217323
TI  - Noninvasive monitoring of physiologic compromise in acute appendicitis: New
      insight into an old disease.
AB  - INTRODUCTION: Physiologic compromise in children with acute appendicitis has
      heretofore been difficult to measure. We hypothesized that the Compensatory
      Reserve Index (CRI), a novel adjunctive cardiovascular status indicator, would be
      low for children presenting with acute appendicitis in proportion to their
      physiological compromise, and that CRI would rise with fluid resuscitation and
      surgical management of their disease. METHODS: Ninety-four children diagnosed
      with acute appendicitis were monitored with a CipherOx CRITM M1 pulse oximeter
      (Flashback Technologies Inc., Boulder, CO). For clarity, CRI=1 indicates supine
      normovolemia, CRI=0 indicates hemodynamic decompensation (systolic blood
      pressure<80mmHg), and CRI values between 1 and 0 indicate the proportion of
      volume reserve remaining before collapse. Results are presented as counts with
      proportion (%), or mean with 95% confidence interval (CI). RESULTS: Mean age was
      11years old (95% CI: 10-12), and 49 (52%) of the children were male. Fifty-four
      (57%) had nonperforated appendicitis and 40 (43%) had perforated appendicitis.
      Mean initial CRI was significantly higher in those with nonperforated
      appendicitis compared to those with perforated appendicitis (0.57, 95% CI: 0.52
      0.63 vs. 0.36, 95% CI: 0.29-0.43; P<0.001). The significant differences in mean
      CRI values between the two groups remained throughout the course of treatment,
      but lost its significance at 2h after surgery (0.63, 95% CI: 0.57-0.70 vs. 0.53,
      95% CI: 0.46-0.61; P=0.05). CONCLUSION: Low CRI values in children with
      perforated appendicitis are indicative of their lower reserve capacity owing to
      peritonitis and hypovolemia. CRI offers a real-time, noninvasive adjunctive tool
      to monitor tolerance to volume loss in children. LEVEL OF EVIDENCE: Study of
      diagnostic test; Level of evidence: Level III.

PMID- 29217324
TI  - [Medical human resources planning in Europe: A literature review of the
      forecasting models].
AB  - BACKGROUND: Healthcare is a labor-intensive sector in which half of the expenses
      are dedicated to human resources. Therefore, policy makers, at national and
      internal levels, attend to the number of practicing professionals and the skill
      mix. This paper aims to analyze the European forecasting model for supply and
      demand of physicians. METHODS: To describe the forecasting tools used for
      physician planning in Europe, a grey literature search was done in the OECD, WHO,
      and European Union libraries. Electronic databases such as Pubmed, Medine, Embase
      and Econlit were also searched. RESULTS: Quantitative methods for forecasting
      medical supply rely mainly on stock-and-flow simulations and less often on
      systemic dynamics. Parameters included in forecasting models exhibit wide
      variability for data availability and quality. The forecasting of physician needs
      is limited to healthcare consumption and rarely considers overall needs and
      service targets. Besides quantitative methods, horizon scanning enables an
      evaluation of the changes in supply and demand in an uncertain future based on
      qualitative techniques such as semi-structured interviews, Delphi Panels, or
      focus groups. Finally, supply and demand forecasting models should be regularly
      updated. Moreover, post-hoc analyze is also needed but too rarely implemented.
      CONCLUSION: Medical human resource planning in Europe is inconsistent. Political
      implementation of the results of forecasting projections is essential to insure
      efficient planning. However, crucial elements such as mobility data between
      Member States are poorly understood, impairing medical supply regulation
      policies. These policies are commonly limited to training regulations, while
      horizontal and vertical substitution is less frequently taken into consideration.

PMID- 29217325
TI  - Protocatechuic acid (PCA) induced a better antiviral effect by immune enhancement
      in SPF chickens.
AB  - Protocatechuic acid (PCA) is an antiviral agent against Avian Influenza virus
      (AIV) and Infectious Bursal Disease (IBD) virus, but its antiviral mechanism is
      unknown. In this study, we evaluated the humoral and cellular responses to PCA in
      specific pathogen-free (SPF) chickens. One hundred forty 35-day-old SPF chickens
      were randomly divided into 7 groups. The birds were inoculated with the
      commercial, attenuated Newcastle Disease Virus (NDV) vaccine and then received
      orally with 10, 20 or 40 mg/kg body weight of PCA for 30 days. Immune organ
      indexes, anti-Newcastle Disease Virus (NDV) antibodies and lymphocyte
      proliferation, but not body weight, were significantly increased in chicken
      treated with 40 mg/kg PCA, compared to the control birds treated with Astragalus
      polysaccharide (ASP). Survival rate was 70% and 60%, respectively, in the
      chickens with 40 mg/kg PCA, 20 mg/kg PCA while 50% survival was found in the
      birds treated with 125 mg/kg ASP. PCA treatment resulted in significantly lower
      viral load and reduced shedding. These results indicate that PCA may improve
      poultry health by enhancing both the humoral and cellular immune response.

PMID- 29217326
TI  - The effects of fish gender on susceptibility to acute Streptococcus agalactiae
      infection in Javanese medaka Oryzias javanicus.
AB  - This study describes the susceptibility of different fish gender following acute
      Streptococcus agalactiae infection by using Javanese medaka Oryzias javanicus as
      test fish. The fish were grouped into four groups, which were: (1) all-male; (2)
      all-female; (3) mixed-gender (1 male: 1 female ratio); and (4) control non
      infected (1 male: 1 female ratio). The fish in group 1, 2 and 3 were
      intraperitoneally exposed to 5.4 * 108 CFU/mL of S. agalactiae, while for group
      4, the fish were exposed using sterile broth. The main clinical signs and
      histopathological changes of infected Javanese medaka were commonly observed in
      S. agalactiae infected fishes. However, no difference on clinical signs and
      histopathological changes of fish in group 1, 2 and 3 were noticed. The Javanese
      medaka mortality in group 1, 2 and 3 were observed from 4 h post infection (hpi)
      to 6 hpi, with the cumulative mortality from 3% to 30%. Then, the mortality
      increased at 12 hpi, with the range from 53% to 80%. However, 100% of the
      infected fish dead at 24 hpi. No clinical sign, histopathological change and fish
      mortality recorded in group 4. Generally, the clinical signs, mortality patterns,
      cumulative mortality and histopathological changes of Javanese medaka infected by
      S. agalactiae did not show any difference between the all-male, all-female and
      mixed-gender groups. This indicates that the susceptibility of fish to S.
      agalactiae infection is not influenced by their gender.

PMID- 29217327
TI  - Changes of adenosinergic system in piglets fed a diet co-contaminated by
      mycotoxin and their effects on the regulation of adenosine.
AB  - The effects of diets co-contaminated with 300 MUg/kg of aflatoxins and 8000
      MUg/kg of fumonisins on adenosinergic system of the pigs weaned at 15 days of age
      were studied. Piglets were inspected daily, and body weight measurement and blood
      collections were performed at every five days. Piglets intoxicated by mycotoxins
      presented lower weight gain (p < 0.001) in comparison to control. Intoxicated
      piglets also showed a reduction in the serum levels of zinc and adenosine and in
      adenosine deaminase (ADA) activity (p < 0.001). Positive correlations between
      zinc levels and ADA activity (p < 0.001) and between adenosine levels and ADA
      activity (p < 0.05) were observed. Ternary plot shows the influence of zinc
      levels on ADA activity and on adenosine levels, suggesting that low zinc levels,
      caused by subclinical mycotoxin intoxication, can cause immunomodulatory effects
      in piglets. We conclude that piglets intoxicated by fumonisins and aflatoxins
      have low ADA activity and adenosine levels in serum. This can be directly related
      to zinc reduction, which is a cofactor for ADA. The co-contamination by these
      mycotoxins in piglet feed impairs growth and immune defenses of the animals,
      adversely affecting animal health and production. Therefore, changes in the
      purinergic pathway may affect the pathogenesis of the disease.

PMID- 29217328
TI  - [A proposal for improving social and health care: The application of an integral
      and integrated model].

PMID- 29217329
TI  - [The changing profile of caregivers of persons aged 65 years and over with
      disabilities within a persisting family care model].
AB  - INTRODUCTION: The increasing participation of women in the workforce may make it
      difficult to sustain the current model of elderly care. The aim of this article
      was to determine the changing sociodemographic profile of informal elderly
      caregivers with disabilities, the interaction between employment and care, and
      the view of the public on the responsibility of that care. MATERIALS AND METHODS:
      Cross-sectional analysis of secondary data from four national surveys were used:
      the disability surveys held in 1999 (N=3,936) and 2008 (N=5,257), the 2011-12
      National Health Survey (N=439), and the Family and Gender survey of 2012
      (N=1,359). They were analysed using contingency tables based on gender and age.
      RESULTS: Half of the informal caregivers were women aged 45 to 64 years. Between
      1999 and 2011-12 they became more concentrated in the 55-64 age-bracket, among
      whom participation in the workforce doubled from 20% to 40%. Increased care for
      men was associated with unemployment. Care work had a negative impact on working
      life, with greater impact among women and those who cared for elderly people with
      severe disabilities. Less likely to consider that elderly care provision should
      rest on family are 45-54 year-old economically active women (only 42%) or those
      who are more educated (40%), compared to 60% of economically inactive women and
      55% of less educated women. CONCLUSIONS: Economically active and educated women
      are less inclined to family-based care, but assume it independently of their
      workforce participation, whereas males do so according to their availability.

PMID- 29217330
TI  - [Cognitive neuroscience of aging. Contributions and challenges].
AB  - The cognitive neuroscience of aging is a young discipline that has emerged as a
      result of the combination of: A) the theoretical and explanatory frameworks
      proposed by the cognitive psychology perspective throughout the second half of
      the twentieth century; B) the designs and methodological procedures arising from
      experimental psychology and the need to test the hypotheses proposed from the
      cognitive psychology perspective; C) the contributions of the computer sciences
      to the explanation of brain functions; and D) the development and use of
      neuroimaging techniques that have enabled the recording of brain activity in
      humans while tasks that test some cognitive process or function are performed. An
      analysis on the impact of research conducted from this perspective over the last
      3decades has been carried out, including its shortcomings, as well as the
      potential directions and usefulness that will advantageously continue to drive
      this discipline in its description and explanation of the process es of cerebral
      and cognitive aging.

PMID- 29217331
TI  - Dosimetric impact of translational and rotational setup errors for spine
      stereotactic body radiotherapy: A phantom study.
AB  - This study aimed to investigate experimentally the effect of translational and
      rotational setup errors on 3-dimensional dose distributions by using the gamma
      index and dose volumetric indices for spine stereotactic body radiotherapy.
      Treatment plans were designed in accordance with the Radiation Therapy Oncology
      Group (RTOG) 0631 protocol. Measurements were taken using a Delta4 phantom
      (ScandiDos, Uppsala, Sweden). Setup errors were generated using the HexaMotion 6D
      moving platform (ScandiDos). Dose distributions in the presence of setup errors
      were evaluated, according to the gamma passing rate with the 3% and 2 mm criteria
      (gamma3%/2 mm) and dose volumetric indices (D90 for the target volume and D2 for
      the spinal cord), using the Delta4 device (ScandiDos). The sensitivity
      coefficient, which represented the correlation between the gamma3%/2 mm passing
      rate and dose volumetric indices, was determined to assess robustness against
      setup errors. Rotational setup errors of 2 degrees  were equivalent to
      translational setup errors of 2 mm for the gamma3%/2 mm passing rate, D90 for the
      target, and D2 for the spinal cord. D90 for the target had low robustness against
      a translational setup error in the vertical direction and a rotational setup
      error in the pitch direction. D2 for the spinal cord was sensitive to a
      translational setup error in the lateral direction and a rotational setup error
      in the roll direction. The positioning accuracy of the rotational setup error,
      corresponding to the tolerance level of image-guided radiotherapy in the RTOG
      0631 protocol, was required to be <= 2 degrees .

PMID- 29217332
TI  - Revisiting high-frequency oscillatory ventilation in vitro and in silico in
      neonatal conductive airways.
AB  - BACKGROUND: High frequency oscillatory ventilation is often used for lung support
      in premature neonates suffering from respiratory distress syndrome. Despite its
      broad use in neonatal intensive care units, there are to date no accepted
      protocols for the choice of appropriate ventilation parameter settings. In this
      context, the underlying mass transport mechanisms are still not fully understood.
      METHODS: We revisit the question of flow phenomena under conventional mechanical
      ventilation and high frequency oscillatory ventilation in an anatomically
      inspired model of neonatal conductive airways spanning the first few airway
      generations. We first perform at true scale in vitro particle image velocimetry
      measurements of respiratory flow patterns. Next, we explore in silico convective
      mass transport in computational fluid dynamics simulations by implementing
      Lagrangian tracking of tracer boli, where the ventilatory flow rate is fixed.
      FINDINGS: Particle image velocimetry measurements at eight representative phase
      angles of a breathing cycle reveal similar flow patterns at peak velocity and
      during deceleration phases for conventional mechanical ventilation and high
      frequency oscillatory ventilation. Characteristic differences occur during the
      acceleration and flow reversal phases. Net displacements of the tracer particles
      rapidly reach asymptotic behaviour over cumulative breathing cycles and suggest a
      linear relation between tidal volume and convective mass transport.
      INTERPRETATION: The linear relation observed suggests that differences in flow
      characteristics between conventional mechanical ventilation and high frequency
      oscillatory ventilation conditions do not substantially influence convective mass
      transport mechanisms. Lower tidal volumes thus cannot be compensated
      straightforwardly by selecting higher frequencies to maintain similar ventilation
      efficiencies.

PMID- 29217333
TI  - Inside job: Staphylococcus aureus host-pathogen interactions.
AB  - Staphylococcus aureus is a notorious opportunistic pathogen causing a plethora of
      diseases. Recent research established that once phagocytosed by neutrophils and
      macrophages, a certain percentage of S. aureus is able to survive within these
      phagocytes which thereby even may contribute to dissemination of the pathogen. S.
      aureus further induces its uptake by otherwise non-phagocytic cells and the
      ensuing intracellular cytotoxicity is suggested to lead to tissue destruction,
      whereas bacterial persistence within cells is thought to lead to immune evasion
      and chronicity of infections. We here review recent work on the S. aureus host
      pathogen interactions with a focus on the intracellular survival of the pathogen.

PMID- 29217334
TI  - Health Literacy: An Important Clinical Tool in Heart Failure.

PMID- 29217335
TI  - Rivaroxaban and Apixaban for Initial Treatment of Acute Venous Thromboembolism of
      Atypical Location.
AB  - OBJECTIVES: To assess the outcome of direct oral anticoagulants (DOACs),
      specifically Xa inhibitors: rivaroxaban and apixaban, for the treatment of venous
      thromboembolism (VTE) of atypical location (VTE-AL), portal, mesenteric, hepatic,
      splenic, gonadal, renal, and cerebral veins, prospectively collected data of Mayo
      Thrombophilia Clinic Registry were used. METHODS: Patients with acute VTE-AL
      treated with DOACs, enrolled between March 1, 2013, and February 1, 2017, were
      compared with patients with VTE of typical location (VTE-TL: deep vein thrombosis
      of extremities and/or pulmonary embolism) receiving DOACs and with patients with
      VTE-AL treated with enoxaparin. RESULTS: Out of 623 patients with acute VTE
      receiving the study drug within 14 days of diagnosis, there were 63 with VTE-AL:
      36 on DOAC, 23 on enoxaparin, and 4 on warfarin; 352 received DOAC for VTE-TL.
      The VTE-AL treated with DOAC/enoxaparin included the following: splanchnic
      (26/22), ovarian (8/2), renal (3/5), and cerebral veins (1/1), respectively.
      Recurrence rate (per 100 person-years) for the VTE-AL group receiving DOAC was
      7.3, which was not different when compared with those for VTE-TL (2.4; P=.13) and
      VTE-AL groups receiving enoxaparin (23.7; P=.37). Major bleeding rate in the VTE
      AL group receiving DOAC was not different compared with those for VTE-TL (7.2 vs
      3.0; P=.26) and VTE-AL groups on enoxaparin (22.4; P=.31). Mortality was higher
      in the VTE-AL group on DOAC compared with the VTE-TL group (21.45 [95% CI, 7.87
      46.69] vs 8.26 [95% CI, 5.35, 12.20]; P=.03). All patients with VTE-AL with
      events had cancer. CONCLUSION: The VTE recurrence and bleeding rates for
      rivaroxaban and apixaban used in VTE-AL are not different from those in patients
      with VTE-TL and similar to that for enoxaparin.

PMID- 29217336
TI  - Patient-Physician Agreement Using Summary Outcome Determination Scores.
AB  - OBJECTIVE: To determine whether the Summary Outcome Determination (SOD) score had
      exhibited a high level of physician-patient agreement in surgical patients.
      PATIENTS AND METHODS: The medical records of 320 postoperative patients were
      reviewed, of whom 164 patients were included in the study. Patients were included
      if both physician-assigned and patient-assigned SOD scores had been recorded. The
      SOD is administered as follows: the patient is asked "Compared to before surgery,
      is your elbow/shoulder better, worse or no different?" If better: "Is it
      improved, greatly improved, almost normal or normal?" If worse: "Is it worse or
      profoundly worse, or as bad as dying?" Each category is associated with a
      numerical value and definition for further clarification. The patient is asked to
      assign a category and a numerical value after the physician has already done so.
      These categories and values were evaluated between raters (ie, physician and
      patient) to assess reliability. RESULTS: The intraclass correlation coefficient
      of physician-patient numerical ratings was "excellent" (0.93). The Bland-Altman
      95% limits of agreement on the differences between the physician and the patient
      ranged from -1.3 to 1.3. The physician and patient numerical rankings matched
      exactly in 118 patients (72%) or differed by a factor of no more than 1 (26%) in
      161 (98%) patients. CONCLUSION: The SOD score can be used as both a surgeon-based
      and a patient-based outcome score, given the high level of agreement. Given its
      brevity, ease of understanding, and high interrater reliability, the SOD has the
      potential to be used across multiple specialties to rate outcomes.

PMID- 29217337
TI  - Health Literacy and Outcomes in Patients With Heart Failure: A Prospective
      Community Study.
AB  - OBJECTIVE: To examine the impact of health literacy on hospitalizations and death
      in a population of patients with heart failure (HF). PATIENTS AND METHODS:
      Residents from the 11-county region in southeast Minnesota with a first-ever
      International Classification of Diseases, Ninth Revision code 428 or Tenth
      Revision code 150 (n=5121) from January 1, 2013, through December 31, 2015, were
      identified and prospectively surveyed to measure health literacy using
      established screening questions. A total of 2647 patients returned the survey
      (response rate, 52%); 2487 patients with complete health literacy data were
      retained for analysis. Health literacy, measured as a composite score on three 5
      point scales, was categorized as adequate (>=8) or low (<8). Cox proportional
      hazards regression and Andersen-Gill models were used to examine the association
      of health literacy with mortality and hospitalization. RESULTS: Of 2487 patients
      (mean age, 73.5 years; 53.6% male [n=1333]), 10.5% (n= 261) had low health
      literacy. After mean +/- SD follow-up of 15.5+/-7.2 months, 250 deaths and 1584
      hospitalizations occurred. Low health literacy was associated with increased
      mortality and hospitalizations. After adjusting for age, sex, comorbidity,
      education, and marital status, the hazard ratios for death and hospitalizations
      in patients with low health literacy were 1.91 (95% CI, 1.38-2.65; P<.001) and
      1.30 (95% CI, 1.02-1.66; P=.03), respectively, compared with patients with
      adequate health literacy. CONCLUSION: Low health literacy is associated with
      increased risks of hospitalization and death in patients with HF. The clinical
      evaluation of health literacy could help design interventions individualized for
      patients with low health literacy.

PMID- 29217338
TI  - [Occupational risks during pregnancy: Feedback from occupational medical
      services].
AB  - OBJECTIVES: To describe the follow-up of pregnancies at work and exposures to
      pregnancy occupational hazards. METHODS: A cross-sectional study was performed
      between January and December 2014 in occupational health services of Languedoc
      Roussillon region. Eligible workers were interviewed by occupational health
      physicians (OHPs) after delivery and at the time of returning to work (exposure,
      anticipation, prevention, communication, sick leave). Occupational skill levels
      were classified according to the French standard classification of occupations
      (version 2003) from the French National Institute of Statistics. Socioeconomic
      deprivation was assessed using the Evaluation of Deprivation and Inequalities in
      Health Examination (EPICES) individual scale. RESULTS: A total of 1347 workers
      were recruited. The mean age was at 30.7+/-4.5 years. Among pregnant workers,
      there were 54.2% of employees, 30.7% of intermediate occupations, 10.4% of
      managers and, 4.7% of manual workers. Twenty-two percent of workers were classed
      as deprived. Also, 43.2% of workers were exposed to three or more occupational
      hazards during pregnancy. Only 17.7% of workers had medical visits with OHP
      during pregnancy and 14.7% benefited from workstation adjustments. In contrast,
      the level of sick leaves was high (74.2%). CONCLUSION: Our results argue for the
      need to follow pregnancies at work. However, the low level of prevention
      activities and the high level of sick leaves raise the question of the management
      of pregnant women at work.

PMID- 29217339
TI  - Standardization, chemical profiling, in vitro cytotoxic effects, in vivo anti
      carcinogenic potential and biosafety profile of Indian propolis.
AB  - BACKGROUND: Propolis from apiculture is known for wide range of medicinal
      properties owing to its vast chemical constituents including polyphenols,
      flavonoids and anticancer agent Caffeic acid phenethyl ester (CAPE). OBJECTIVES:
      The objective of the study was to extract and standardize Indian propolis (IP)
      with respect to selected markers by newly developed High performance liquid
      chromatography (HPLC) method, to evaluate in vitro and in vivo anticancer
      activity and biosafety of Indian propolis. MATERIALS AND METHODS: IP was
      extracted, optimized and standardized using a newly developed and validated HPLC
      method for simultaneous estimation of caffeic acid, apigenin, quercetin and CAPE.
      The standardised ethanolic extract of IP (EEIP) was screened for in vitro
      cytotoxicity using sulforhodamine B (SRB) assay, in vivo anti-carcinogenic effect
      against Dalton's Lymphoma ascites (DLA) cells, hemolytic effect and pesticide
      analysis. RESULTS: The EEIP was found to contain more amount of total flavonoids
      (23.61+ 0.0452 mg equivalent of quercetin/g), total polyphenolics (34.82 + 0.0785
      mg equivalent of gallic acid/g) and all selected markers except caffeic acid
      compared to all other extracts. EEIP showed better anti-cancer potential than
      CAPE on MCF-7 and HT-29 cell line and significant (p < 0.01) in vivo anti
      carcinogenic effects against DLA in comparison with 5-fluorouracil. EEIP was
      found to be non-hemolytic. CONCLUSION: From in vitro cytotoxicity, in vivo anti
      carcinogenicity and biosafety studies it can be concluded that the standardized
      EEIP is safe and can be considered for further development as a biomedicine.

PMID- 29217340
TI  - SUPERA stent outcomes in Above-The-Knee IntervEntions: Effects of COMPression and
      ELongation (SAKE-COMPEL) Sub-study.
AB  - INTRODUCTION: The interwoven nitinol design of the Supera stent has been shown to
      have superior radial strength and fracture resistance resulting in higher patency
      rates at 6 and 12months. A detailed sub-analysis of SUPERB trial showed
      differences in patency based on stent conformation post deployment. We evaluated
      the patency of the stent within the SAKE study cohort based on stent deployment
      conformation. METHODS: We retrospectively evaluated the medical records of 63
      patients (77 limbs) with Rutherford class 2-5 symptoms who received Supera stents
      in the femoro-popliteal artery from March 2010 through May 2011 as part of the
      SAKE study. These patients were followed for patency and the need for re
      intervention over a mean follow up of 15months. Compression or Elongation was
      defined as follows based on previous sub-analyses: Moderate Compression (-40 to 
      21%); Minimal Compression (-20 to -11%); Nominal (-10 to 10%); Minimal Elongation
      (11 to 20%); Moderate Elongation (21 to 40%); and Severe Elongation (>40%).
      Significance was determined using Chi X2 test. RESULTS: The best patency rates
      (85.2% primary patency and 92.6% assisted primary patency) and lowest re
      intervention rates (14.8%) were achieved with stent compression, followed by
      nominal deployment or minimal elongation, and worst outcomes (64.7% primary
      patency; 82.3% assisted primary patency; and 35.3% re-intervention) with stent
      elongation to moderate or severe degree. CONCLUSIONS: Patency rates and re
      intervention rates are variable based on deployment characteristics of the Supera
      stent. Best outcomes are achieved with compression of the stent during
      deployment.

PMID- 29217341
TI  - Coronary artery disease reporting and data system (CAD-RADSTM): Inter-observer
      agreement for assessment categories and modifiers.
AB  - BACKGROUND: The Coronary Artery Disease Reporting and Data System (CAD-RADS)
      provides a lexicon and standardized reporting system for coronary CT angiography.
      OBJECTIVES: To evaluate inter-observer agreement of the CAD-RADS among an panel
      of early career and expert readers. METHODS: Four early career and four expert
      cardiac imaging readers prospectively and independently evaluated 50 coronary CT
      angiography cases using the CAD-RADS lexicon. All readers assessed image quality
      using a five-point Likert scale, with mean Likert score >=4 designating high
      image quality, and <4 designating moderate/low image quality. All readers were
      blinded to medical history and invasive coronary angiography findings. Inter
      observer agreement for CAD-RADS assessment categories and modifiers were assessed
      using intra-class correlation (ICC) and Fleiss' Kappa (kappa).The impact of
      reader experience and image quality on inter-observer agreement was also
      examined. RESULTS: Inter-observer agreement for CAD-RADS assessment categories
      was excellent (ICC 0.958, 95% CI 0.938-0.974, p < 0.0001). Agreement among expert
      readers (ICC 0.925, 95% CI 0.884-0.954) was marginally stronger than for early
      career readers (ICC 0.904, 95% CI 0.852-0.941), both p < 0.0001. High image
      quality was associated with stronger agreement than moderate image quality (ICC
      0.944, 95% CI 0.886-0.974 vs. ICC 0.887, 95% CI 0.775-0.95, both p < 0.0001).
      While excellent inter-observer agreement was observed for modifiers S (stent) and
      G (bypass graft) (both kappa = 1.0), only fair agreement (kappa = 0.40) was
      observed for modifier V (high risk plaque). CONCLUSION: Inter-observer
      reproducibility of CAD-RADS assessment categories and modifiers is excellent,
      except for high-risk plaque (modifier V) which demonstrates fair agreement. These
      results suggest CAD-RADS is feasible for clinical implementation.

PMID- 29217342
TI  - Cinematic rendering of cardiac CT volumetric data: Principles and initial
      observations.
AB  - BACKGROUND: Cinematic rendering (CR) a new method of 3D computed tomography (CT)
      volumetric visualization that produces photorealistic images. As with traditional
      3D visualization methods, CR may prove to be of value in providing important
      information when evaluating regions of complex anatomy such as the heart.
      METHODS: The gated, IV contrast-enhanced chest CT angiogram data from three
      recent patients were evaluated with CR. Image comparision demonstrates the
      difference between CR and traditional volume rendering (VR), owing to a more
      complex lighting model that enhances surface detail and produces realistic
      shadows to add depth to 3D visualizations. RESULTS: Representative examples of
      normal cardiac anatomy, a coronary artery stenosis, and an intracardiac malignant
      neoplasm are presented with 2D multiplanar reconstruction, traditional VR and CR.
      A potential pitfall in CR utilization, namely the possibility of obscuring
      important pathology, is demonstrated and discussed. CONCLUSIONS: CR is a
      promising method to enhance display volumetric CT data and should prove useful in
      diagnosis, treatment planning, surgical navigation, trainee education, and
      patient engagement. However, further study is needed to establish the advantaged
      and disadvantages of CR in comparison to other 3D methods.

PMID- 29217344
TI  - Factors associated with in-hospital mortality among critically ill surgical
      patients with multidrug-resistant Gram-negative infections: Methodological
      issues.

PMID- 29217343
TI  - Patent foramen ovale in patients with pulmonary embolism: A prognostic factor on
      CT pulmonary angiography?
AB  - BACKGROUND: Patent foramen ovale (PFO) in patients with acute pulmonary embolism
      (PE) represents a risk factor for mortality, but this has not been evaluated for
      CT pulmonary angiography (CTPA). The purpose of the present study was to assess
      the relationship between PFO and mortality in patients with acute PE diagnosed on
      CTPA. MATERIALS AND METHODS: This retrospective study included 268 adults [173
      women, mean age 61 (range 22-98) years] diagnosed with acute PE on non-ECG-gated
      64-slice CTPA in 2012 at our medical center. The images were reviewed for PFO by
      a panel of cardiothoracic radiologists with an average of 11 years of experience
      (range 1-25 years). CT signs of right heart strain and PE level were noted.
      Transthoracic echocardiograms (TTE), when available (n = 207), were reviewed for
      PFO by a cardiologist with subspecialty training in advanced imaging and with 3
      years of experience. The main outcome was 30-day mortality. Fischer's exact test
      was utilized to compare mortality. RESULTS: PFO prevalence on CTPA was 22%
      (58/268) and 4% (9/207) on TTE. Overall 30-day mortality was 6% (16/268), 9%
      (5/58) for patients with PFO and 5% (11/210) for those without (p = 0.35). CT
      signs of right heart strain trended with higher mortality, but statistically
      significant only for hepatic vein contrast reflux [14% (6/44) vs 4% (10/224), p =
      0.03]; right ventricular (RV) to left ventricular (LV) diameter ratio >1 [8%
      (13/156) vs RV:LV <= 1 3% (3/112), p = 0.07], septal bowing [10% (4/42) vs
      without 5% (12/226), p = 0.30]. CONCLUSION: PFO was demonstrated on CTPA in a
      proportion similar to the known population prevalence, while routine TTE was less
      sensitive. Mortality was non-significantly higher in patients with acute PE and
      PFO in this moderate-sized study. A larger study to answer this clinically
      important question is worthwhile.

PMID- 29217345
TI  - Severe community-acquired Capnocytophaga leadbetteri pneumonia in a HIV-infected
      patient.

PMID- 29217346
TI  - Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case
      control study from Denmark.
AB  - BACKGROUND: Hydrochlorothiazide, one of the most frequently used diuretic and
      antihypertensive drugs in the United States and Western Europe, is
      photosensitizing and has previously been linked to lip cancer. OBJECTIVE: To
      examine the association between hydrochlorothiazide use and the risk of basal
      cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: From the Danish
      Cancer Registry, we identified patients (cases) with nonmelanoma skin cancer
      (NMSC) during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative
      hydrochlorothiazide use (in 1995-2012) was assessed from the Danish Prescription
      Registry. Using conditional logistic regression, we calculated odds ratios (ORs)
      for BCC and SCC associated with hydrochlorothiazide use. RESULTS: High use of
      hydrochlorothiazide (>=50,000 mg) was associated with ORs of 1.29 (95% confidence
      interval [CI], 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. We found
      clear dose-response relationships between hydrochlorothiazide use and both BCC
      and SCC; the highest cumulative dose category (>=200,000 mg of HCTZ) had ORs of
      1.54 (95% CI, 1.38-1.71) and 7.38 (95% CI, 6.32-8.60) for BCC and SCC,
      respectively. Use of other diuretics and antihypertensives was not associated
      with NMSC. LIMITATIONS: No data on sun exposure were available. CONCLUSIONS:
      Hydrochlorothiazide use is associated with a substantially increased risk of
      NMSC, especially SCC.

PMID- 29217347
TI  - Risky business: Adjusting the pressure of the artificial urinary sphincter
      reservoir.

PMID- 29217348
TI  - Urethral pressure controlled balloon refilling or balloon change for artificial
      sphincter secondary procedure?
AB  - OBJECTIVES: To report our experience of inflating or changing pressure balloon to
      treat recurrent urinary incontinence after AMS800(r) implantation instead of
      changing all the devices. PATIENTS AND METHODS: A retrospective study was
      conducted in a tertiary reference center between 2005 and 2015. All patients,
      treated by AMS800(r) implantation for post-prostatectomy urinary incontinence and
      whom balloon was subsequently changed or inflated, were included. Main clinical
      end point was the need for another surgery. Secondary end points were urethral
      erosion, infection, and efficacy on pad test and pad use. RESULTS: Thirty-one
      patients were included. All had had a 61-70cm H20 balloon implanted, with a
      single cuff (13 with transcorporeal placement). Twenty-one patients had their
      balloon changed for a 71-80cm H20 type, while 10 patients had their balloon
      refilled (median 3mL [range 2-7]). Median follow-up was 23 months (range 1-129).
      Overall rate of another subsequent surgery was 48.3% (n=15). Erosion and atrophy
      occurred more frequently after balloon repressurizing than after balloon
      replacement (80% vs 33%, P=0.024). At last follow-up, median pad use was higher
      in repressurizing group (2 vs 1, P=0.033). CONCLUSION: Balloon repressurizing is
      associated with a higher erosion and reoperation rate than changing pressure
      balloon. Continence results seem better when PRB is changed. It could be an
      alternative instead of changing all devices in patients with frail urethra. LEVEL
      OF EVIDENCE: 4.

PMID- 29217349
TI  - Arthrodesis of the proximal interphalangeal joint of the 4th and 5th finger using
      an interlocking screw device to treat severe recurrence of Dupuytren's disease.
AB  - OBJECTIVE: To assess the radiological and functional outcome of arthrodesis of
      the 4th and 5th finger using the APEXTM (Extremity Medical,
      Parsippany,NJ)intermedullary interlocking screw system in patients with severe
      recurrence of Dupuytren's disease. MATERIAL AND METHOD: The DASH questionnaire
      and the VAS scale were used to assess the clinical outcomes. The angle of
      arthrodesis, fusion time and implant fixation were evaluated on x-rays. The
      patients were monitored for complications during surgery and the follow-up
      period. RESULTS: The sample comprised 6 patients. Mean follow up was 19.6 months.
      All of the patients presented clinical and radiological evidence of fusion at 8
      weeks, with fusion angles of 30 degrees  (3) and 45 degrees  (3). There were no
      complications and none of the implants had to be removed. The functional outcomes
      in these patients were poor. CONCLUSION: The system offers a reliable method for
      IPJ arthrodesis at a precise angle. It promotes stable fixation that does not
      require prolonged immobilisation. It can be used together with other procedures
      on the hand with severe recurrence of DD. The functional outcomes for this group
      of patients using this device were poor.

PMID- 29217350
TI  - Clinical factors that affect perceived quality of life in arthroscopic
      reconstruction for acromioclavicular joint dislocation.
AB  - OBJECTIVE: To analyse the results of arthroscopic repair of acromioclavicular
      dislocation in terms of health-related quality of life. MATERIAL AND METHOD:
      Prospective study of patients with acromioclavicular dislocation Rockwood grade
      iii-v, treated arthroscopically with a mean follow up of 25.4 months. The
      demographics of the series were recorded and evaluations were performed
      preoperatively, at 3 months and 2 years with validated questionnaires as Short
      Form-36 Health Survey (SF-36), visual analogue scale (VAS), The Disabilities of
      the Arm, Shoulder and Hand (DASH), Constant-Murley Shoulder Outcome Score
      (Constant) and Walch-Duplay Score (WD). RESULTS: Twenty patients, 17 men and 3
      women with a mean age of 36.1 years, were analysed. According to the
      classification of Rockwood, 3 patients were grade iii, 3 grade iv and 14 grade v.
      Functional and clinical improvement was detected in all clinical tests (SF-36,
      VAS and DASH) at 3 months and 2 years follow up (P<.001). The final Constant
      score was 95.3+/-2.4 and the WD was 1.8+/-0.62. It was not found that the health
      related quality of life was affected by any variable studied except the evolution
      of DASH. CONCLUSIONS: The health-related quality of life (assessed by SF-36) in
      patients undergoing arthroscopic repair of acromioclavicular joint dislocation
      grades iii-v was not influenced by gender, age, grade, displacement, handedness,
      evolution of the VAS, scoring of the Constant or by the WD. However, it is
      correlated with the evolution in the DASH score.

PMID- 29217351
TI  - Endophthalmitis: Then and Now.
AB  - PURPOSE: To report historically evolving strategies (then and now) in prevention
      and management of endophthalmitis. DESIGN: A perspective on relevant topics in
      the prophylaxis and management of endophthalmitis. METHODS: This is an author
      selected review of studies leading to changes in strategies for endophthalmitis
      management over the last 100 years. RESULTS: The current perspective discusses
      the trends and strategies over the past century. Historically, 3 endophthalmitis
      time-periods have existed and include the pre-antimicrobial era, the
      predominantly systemic antimicrobial era, and the current intravitreal
      antimicrobial era. The management of endophthalmitis from different etiologies,
      including endogenous, postinjection, post-cataract surgery, and other anterior
      segment-related (eg, post-penetrating keratoplasty), bleb-associated, glaucoma
      drainage device-associated, and open globe injury-associated, are discussed.
      Specific etiologies may predict most common microbial causes and may guide
      differing management strategies. Pars plana vitrectomy offers theoretical
      advantages but is generally reserved for patients with more advanced disease.
      CONCLUSIONS: Despite advances over the past 100 years, endophthalmitis is an
      important sight-threatening complication. Timely management with the appropriate
      use of antimicrobial agents may optimize visual outcomes.

PMID- 29217352
TI  - Relationship between individual categories of adverse childhood experience and
      diabetes in adulthood in a sample of US adults: Does it differ by gender?
AB  - AIMS: ACEs are known to increase risk for diabetes in adulthood. However, little
      is known about the differential impact of individual ACE categories on diabetes
      risk, and whether this relationship is gender specific. METHODS: Data from the
      2011 BRFSS was used in this study. Participants included 48,526 adults who
      completed the ACE module across 5 states. Using logistic regression, we examined
      the odds of diabetes in adulthood related to eight individual categories of ACEs:
      sexual abuse, physical abuse, verbal abuse, mental illness, substance abuse,
      incarceration, separation/divorce, and violence. A gender interaction term was
      included to test if this relationship varied between men and women. RESULTS: In
      adjusted analyses, sexual abuse (OR 1.57, CI 1.240; 1.995) had the strongest
      positive association followed by verbal (OR 1.29, CI 1.117; 1.484) and physical
      abuse (OR 1.26, CI 1.040; 1.516). Having a parent with mental illness was also
      significantly associated with increased odds of diabetes (OR 1.19, CI 0.996;
      1.416). No interaction between ACEs and diabetes status by gender in any of the
      eight categories was found. CONCLUSIONS: Overall, this study found that four ACE
      categories were significantly associated with increased odds of diabetes in
      adulthood with sexual abuse being the strongest predictor.

PMID- 29217353
TI  - Policy on Posthumous Sperm Retrieval: Survey of 75 Major Academic Medical
      Centers.
AB  - OBJECTIVE: To evaluate the presence and content of policies on posthumous sperm
      retrieval at 75 major academic medical centers in the U.S. MATERIALS AND METHODS:
      We surveyed the top 75 major academic medical centers ranked for research in 2016
      by U.S. News & World Report using a questionnaire-based telephone/web survey. We
      gathered data on the presence and content of posthumous sperm retrieval policies
      on the Internet. If not published, we contacted the legal counsel, the ethics and
      compliance offices, the urology department, as well as the infertility treatment
      center associated with each institution. In addition, we also surveyed members of
      the Society for Male Reproduction and Urology. RESULTS: We gathered data
      regarding posthumous sperm retrieval from 41 out of the 75 major academic medical
      centers. Of the 41 institutions, only 11 (26.8%) had policies regarding
      posthumous sperm retrieval. Out of those 11 centers, 4 required prior written
      consent, whereas the remaining 6 allowed for verbal or inferred consent from the
      surviving life partner. One policy prohibited the procedure. Five of the policies
      in this survey included a bereavement period. Of the 30 (73.2%) centers without
      policies, lack of legal guidance was cited as the most common barrier to policy
      adoption. CONCLUSION: Only a small proportion of major academic medical centers
      have policies on posthumous sperm retrieval. Medical centers can adopt
      individualized policies based on guidelines published by professional societies.

PMID- 29217354
TI  - Prostate Magnetic Resonance Imaging Provides Limited Incremental Value Over the
      Memorial Sloan Kettering Cancer Center Preradical Prostatectomy Nomogram.
AB  - OBJECTIVE: To examine the incremental value of prostate magnetic resonance
      imaging (MRI) when used in combination with the currently available preoperative
      risk stratification tool, the Memorial Sloan Kettering Cancer Center (MSKCC)
      preradical prostatectomy nomogram. MATERIALS AND METHODS: We reviewed our
      institutional database of prostate MRI performed before radical prostatectomy
      between December 2014 and March 2016 (n = 236). We generated a logistic
      regression model based on observed final pathology results and the MSKCC nomogram
      predictions for organ-confined disease, extracapsular extension (ECE), seminal
      vesicle invasion, and lymph node involvement (LNI) ("MSKCC only"). We then
      generated a combined regression model incorporating both the MSKCC nomogram
      prediction with the degree of prostate MRI suspicion ("MSKCC + MRI"). Receiver
      operating characteristic curves were generated, and the area under the curves
      (AUCs) were compared. RESULTS: When independently examining the MSKCC nomogram
      predicted risk and the degree of prostate MRI suspicion, MRI was a predictor for
      ECE (odds ratio 2.8, P <.01) and LNI (odds ratio 5.6, P = .01). When examining
      the "MSKCC + MRI" and "MSKCC only" models, the incremental benefit in risk
      discrimination from the combined model ("MSKCC + MRI") was not significant for
      organ-confined disease, ECE, seminal vesicle invasion, or LNI (DeltaAUC +0.03, P
      = .10; DeltaAUC +0.03, P = .08; DeltaAUC 0.63, P = .63; DeltaAUC +0.04, P = .42;
      respectively). CONCLUSION: A combined model with prostate MRI and the MSKCC
      nomogram provides no additional risk discrimination over the MSKCC nomogram-based
      model alone. Evaluation of prostate MRI as a predictive tool should be performed
      in combination with, not independent of, these clinical risk stratification
      models.

PMID- 29217355
TI  - Crocetin attenuates spared nerve injury-induced neuropathic pain in mice.
AB  - Crocetin is the main component of saffron and exhibits anti-oxidative and anti
      inflammatory effects. Neuroinflammation and oxidative stress have been recognized
      to play a crucial role in the pathogenesis of neuropathic pain. We investigated
      the effect of crocetin in a mouse model with neuropathic pain induced by spared
      nerve injury (SNI). Crocetin was intrathecally perfused at various doses for up
      to 12 days starting 3 days before the surgery. Behavioral tests were performed to
      determine pain sensitivity. The concentrations of proinflammatory cytokines tumor
      necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta) were measured to
      assess neuroinflammation. In addition, the enzymatic activity of superoxide
      dismutase (SOD) was measured to reveal the oxidative stress level. We found that
      repeated treatment with crocetin dose-dependently attenuated mechanical and
      thermal allodynia in SNI mice. In addition, treatment with high dose of crocetin
      reduced SNI-induced increase of TNF-alpha and IL-1beta. Crocetin also restored
      the activity of mitochondrial MnSOD which was reduced in the sciatic nerve and
      the spinal cord of SNI mice. Collectively, our data demonstrate that crocetin
      effectively attenuates the neuropathic pain and significantly suppresses
      oxidative stress and neuroinflammation in the SNI mouse model, supporting the
      potential of crocetin in the treatment against neuropathic pain.

PMID- 29217356
TI  - Improved stratification of pT1 melanoma according to the 8th American Joint
      Committee on Cancer staging edition criteria: A Dutch population-based study.
AB  - INTRODUCTION: The 8th American Joint Committee on Cancer (AJCC) staging edition
      includes revisions regarding pT1 melanomas. We aimed to evaluate the expected
      impact of this edition on staging and survival in the Dutch pT1 melanoma
      population. METHODS: In total, 32,935 pT1 melanoma patients, whose data were
      retrieved from the Netherlands Cancer Registry between 2003 and 2015, were
      included in the study. Patients were stratified by the 6th AJCC edition (cohort
      1: 2003-2009) and 7th edition (cohort 2: 2010-2015) and all reclassified
      according to the 8th edition. Stage migration, sentinel lymph node biopsy (SLNB)
      positivity rates and relative survival were analysed. Agreement between staging
      systems was calculated by Cohen's kappa coefficient. RESULTS: In cohort 2,
      restaging according to the 8th edition led to an increase of 7% in the total
      number of patients staged pT1b. The kappa score for agreement between the 6th and
      8th edition was 0.15 and 0.25 for agreement between 7th and 8th edition.
      Restaging according to the 8th edition resulted in a higher SLNB positivity rate
      for pT1b patients than pT1a patients (8% versus 5%, p = 0.08). Relative survival
      curves were predominantly similar between the staging editions. CONCLUSIONS:
      Implementation of the 8th AJCC staging edition will presumably not have major
      impact on the total number of Dutch pT1b patients. Consequently, the number of
      patients eligible for SLNB would roughly remain similar. In terms of SLNB
      positivity, the selection of high-risk pT1 melanoma patients is likely to
      improve. In addition, the 8th edition criteria for pT1 melanoma seem more
      workable for pathologists.

PMID- 29217357
TI  - Tempol prevents post-traumatic stress disorder induced memory impairment.
AB  - Post-traumatic stress disorder (PTSD) is a mental health disorder that can
      develop after a terrifying or life threatening event. Multiple symptoms are
      noticed in patients with PTSD including cognitive impairment, which was shown to
      be is associated with oxidative stress. Tempol is a highly efficient membrane
      permeable antioxidant. In this study, we investigated the possible protective
      effect of tempol on PTSD-induced memory impairment. To test this hypothesis, we
      used single prolonged stress (SPS) model (2h restrain, 20min forced swimming,
      15min rest, and 1-2min diethyl ether exposure) as a model of PTSD. Rats were
      randomly assigned into four groups: control (provided distilled water), tempol
      (provided tempol; 80mg/kg/day by oral gavage for 4weeks), SPS (exposed to
      prolonged stress and administered distilled water) and tempol/SPS (exposed to
      prolonged stress and administered tempol for 4weeks). We used radial arm water
      maze to test spatial learning and memory functions and enzyme-linked
      immunosorbant assay (ELISA) to measure levels of oxidative stress biomarkers in
      the hippocampus. Results showed that SPS model of PTSD impaired both short and
      long-term memories (P<0.05), and chronic tempol administration prevented such
      effect. Tempol also prevented decreases in hippocampal catalase, and SOD
      activities, GSH/GSSG ratio and increases TBARS levels, which were all impaired by
      SPS model of PTSD (P<0.05). In conclusion, we suggest a protective effect of
      tempol administration against SPS model of PTSD-induced short- and long- term
      memory impairment, and we believe that this protective effect of tempol is
      accomplished, at least partly, through prevention of alternation in oxidative
      stress in the hippocampus.

PMID- 29217358
TI  - Lack of agreement between objective and subjective measures in the evaluation of
      masticatory function: A preliminary study.
AB  - The evaluation of mastication is important to understand the masticatory behavior
      and diagnose feeding difficulties. The objective of this preliminary study was to
      verify if there is agreement between objective and subjective validated methods
      of chewing evaluation in a convenience sample which consisted of 32 adolescents
      (mean 15.5years), complete permanent dentition and free of tooth decay. The
      Quality of Masticatory Function Questionnaire with the Food-Mastication, Habits,
      Meat, Fruit and Vegetables domains was used in the subjective evaluation. The
      objective aspects consisted of maximum bite force (BF) and masticatory
      performance (MP) by mastication of cubes of test-material and sieving to
      determine the median particle size (X50) and distribution in the sieves ("b"),
      and by the colorimetric method using colorchangeable chewing gum. Data were
      submitted to exploratory analysis, normality test and correlation tests
      (Pearson/Spearman). The correlation between BF and X50 (r=-0.43; p=0.02) and
      between BF and MP chewing gum (r=0.53; p=0.002) was significant with large effect
      size. The MP evaluated by chewing gum correlated with X50 (r=-0.34; p=0.055), but
      not with "b" (r=-0.06; p=0.73), while "b" correlated only with X50 (r=0.52,
      p=0.002). No significant correlation was observed between the objective measures
      and the total score of the subjective evaluation; only a negative correlation was
      observed between "b" and Meat domain (r=-0.40; p=0.023). The objective methods
      showed moderate correlation with each other and no agreement between the
      objective and subjective methods was observed in this sample of healthy
      adolescents, emphasizing the importance of both aspects in the evaluation of
      masticatory function.

PMID- 29217359
TI  - Impact of tumor size on the prognosis of hepatocellular carcinoma in patients who
      underwent liver resection.
AB  - BACKGROUND: Health burdens of hepatocellular carcinoma (HCC) are emerging quickly
      in the world, including in Taiwan. Surgical resection has been recognized as the
      first-line treatment for early tumors. This study aimed to investigate the
      prognostic risk factors for mortality and recurrence rate in Taiwan, which has a
      high prevalence of chronic viral hepatitis. METHODS: A total of 397 HCC patients
      receiving tumor resection were consecutively examined in central Taiwan from 2008
      to 2014. A hospital-based patient cohort was designed to collect serological
      markers to further assess liver function. We modified the Kaplan-Meier method
      according to the competing death risks for comparing recurrence and used
      multivariate Cox proportional hazard regression to adjust for significant risk
      factors. RESULTS: In addition to advanced fibrosis, tumor size >=5 cm was
      significantly associated with higher mortality within the 5-year period when
      compared with <5 cm (43.3% vs. 13.2%, p < 0.0001). Patients with tumor size >=5
      cm also easily progressed to early recurrence within two years when accounting
      for death as a competing risk (20.1% vs. 10.1%, p = 0.01). Higher AFP levels
      played a major role in further predicting higher mortality in those patients. We
      determined that there were a 4.5-fold and 2.2-fold higher mortalities in patients
      with size >=5 cm/AFP >=20 ng/mL and with size >=5 cm/AFP< 20 ng/mL, respectively,
      when compared to patients with small tumors. CONCLUSION: Tumor size >=5 cm might
      be a good predicting factor for death and early recurrence when considering death
      as a competing risk.

PMID- 29217360
TI  - Sonographic findings of painful hemiplegic shoulder after stroke.
AB  - BACKGROUND: Hemiplegic shoulder pain is common in stroke patients and can
      influence rehabilitation outcome. The underlying pathology can be various: in
      addition to impaired motor control and altered peripheral and central nervous
      activity, soft tissue lesions may also play an important role. It remains unclear
      how these pathologies may interact or correlate with each other. METHODS: This
      retrospective study collected data from 26 stroke patients who received
      sonography examination due to shoulder pain. Severity of soft tissue lesion over
      the shoulder joint was graded on the basis of the sonographic findings. The
      information regarding cognition, sensory function, spasticity (measured by the
      Modified Ashworth Scale) and the Brunnstrom stage of motor recovery was collected
      though medical chart review. This study examined the association between
      sonographic findings and the clinical findings. RESULT: This study showed that
      sonographic grading of painful hemiplegic shoulder is not statistically
      associated with impaired cognition and sensory function. (p value = 0.0587 and
      0.9776, respectively) In addition, there is no correlation between sonographic
      grading and motor recovery in patients with hemiplegic shoulder pain. (Spearman's
      correlation coefficient = -0.0053, p value = 0.9796) Neither is there any
      statistically significant correlation between sonographic grading and the degree
      of spasticity. (Spearman's correlation coefficient = -0.0311, p value = 0.8801).
      CONCLUSION: The results of this study suggests that the mechanism through which
      soft tissue lesions causes hemiplegic shoulder pain may be independent of the
      mechanisms through which changes of muscle tone and nervous activity causes
      shoulder pain.

PMID- 29217361
TI  - Major Adipokines and the -420C>G Resistin Gene Polymorphism as Predictors of
      Acute Ischemic Stroke Severity and In-Hospital Outcome.
AB  - BACKGROUND: The role of adiponectin, leptin, and resistin and the -420C>G
      polymorphism of the resistin gene promoter in the pathogenesis of ischemic stroke
      are controversial. We aimed to evaluate whether serum levels of these adipokines
      and the -420C>G polymorphism are associated with ischemic stroke severity and in
      hospital outcome. METHODS: We prospectively studied 93 patients who were
      consecutively hospitalized for acute ischemic stroke (39.8% males, age 79.7 +/-
      6.3 years). Stroke severity was evaluated at admission by the National Institutes
      of Health Stroke Scale (NIHSS). In-hospital outcome was evaluated by dependency
      rates at discharge and in-hospital mortality. RESULTS: The G allele was more
      prevalent in patients with severe stroke (P < .05). Independent predictors of
      severe stroke were high-sensitivity C-reactive protein levels (relative risk [RR]
      1.43, 95% confidence interval [CI] 1.08-1.91, P < .05). Patients with dependency
      at discharge had lower serum leptin levels (P < .05). Independent predictors of
      functional dependence were prior ischemic stroke (RR 7.55, 95% CI 1.69-33.58, P <
      .01), serum triglyceride levels (RR .98, 95% CI .96-0.99, P < .05), and NIHSS at
      admission (RR 1.47, 95% CI 1.17-1.84, P < .001). The G allele was more prevalent
      in patients who died (P < .05). Independent predictors of in-hospital mortality
      were systolic blood pressure (RR 1.09, 95% CI 1.01-1.19, P < .05) and NIHSS at
      admission (RR 1.26, 95% CI 1.08-1.48, P < .005). CONCLUSIONS: The G allele of the
      -420C>G polymorphism of the resistin gene promoter appears to be associated with
      more severe stroke and higher in-hospital mortality in patients with acute
      ischemic stroke. Higher leptin levels appear to be related to favorable
      functional outcome.

PMID- 29217362
TI  - Rethinking Prehospital Stroke Notification: Assessing Utility of Emergency
      Medical Services Impression and Cincinnati Prehospital Stroke Scale.
AB  - BACKGROUND AND PURPOSE: Although prehospital stroke notification has improved
      stroke treatment, incorporation of these systems into existing infrastructure has
      resulted in new challenges. The goal of our study was to design an effective
      prehospital notification system that allows for early and accurate identification
      of patients presenting with acute stroke. METHODS: We conducted a retrospective
      single-center cohort study of patients presenting with suspicion of acute stroke
      from 2014 to 2015. Data recorded included patient demographics, time of symptom
      onset, Cincinnati Prehospital Stroke Scale (CPSS) score, Glasgow Coma Scale
      score, National Institutes of Health Stroke Scale (NIHSS) score, emergency
      medical services (EMS) impression, acute stroke pager activation, acute
      intervention, and discharge diagnosis. Univariate logistic regression was
      performed with discharge diagnosis of stroke as the end point. RESULTS: A total
      of 130 patients were included in the analysis; 96 patients were discharged with a
      diagnosis of stroke or transient ischemic attack. Both NIHSS and the presence of
      face, arm and speech abnormalities on CPSS were significantly higher in patients
      with stroke (P < .05). EMS correctly recognized stroke in 77.1% of cases but
      falsely identified stroke in 85.3% of negative cases. CPSS identified 75% of
      acute stroke cases, but specificity was poor at only 20.6%. All patients
      receiving intervention had acute stroke pager activation in Emergency Department.
      CONCLUSIONS: Prehospital stroke notification systems utilizing EMS impressions
      and stroke screening tools are sensitive but lack appropriate specificity
      required for modern acute stroke systems of care. Better solutions must be
      explored so that prehospital notification can keep pace with advances in acute
      stroke treatment.

PMID- 29217363
TI  - Positional Brain Single-Photon Emission Computed Tomography Findings in a Case of
      Limb-Shaking Syndrome.
AB  - An 84-year-old man, who presented lower limbs limb-shaking syndrome at
      orthostatism lasting a few seconds, was referred in our stroke unit. Magnetic
      resonance imaging showed an acute infarction in the right thalamus and the
      insular cortex, left extracranial carotid stenosis at 80%, and low flow in the
      right middle cerebral artery but did not explain limb-shaking syndrome
      symptomatology. We performed comparative positional brain perfusion single-photon
      emission computed tomography (SPECT), in the upright and in the supine position,
      to explore and localize hypoperfusion-endangered brain structures that may be
      involved in the presenting symptoms. Brain perfusion SPECT showed deep
      hypoperfusion in bilateral carotid territories in the upright position in favor
      of a hemodynamic mechanism, on which blood pressure was maintained higher to
      avoid hypoperfusion and the patient remained supine for a longer period of time
      than in the usual support. Late postoperative brain perfusion SPECT after left
      endarterectomy did not show significant abnormalities. Limb-shaking syndrome may
      be related to a transient decrease in blood pressure and cerebral blood flow
      caused by postural changes. Positional brain perfusion SPECT seems to be helpful
      to improve clinical care. Positional brain perfusion SPECT should be discussed in
      the acute phase of stroke and if there are involuntary movements.

PMID- 29217364
TI  - Collaterals Predict Outcome Regardless of Time Last Known Normal.
AB  - BACKGROUND AND PURPOSE: Recent studies suggest that patients with large-vessel
      ischemic strokes (large-vessel occlusion [LVO]) with favorable imaging may
      benefit from mechanical thrombolysis even when treated outside the standard 6
      hour window. However, many patients in these studies presented with unknown times
      of onset. We compare outcomes in thrombectomy patients treated at less than
      versus greater than 6 hours from last known well (LKN), and evaluate whether
      "unknown time of onset" alters prognosis. METHODS: We retrospectively reviewed
      patients at 2 comprehensive stroke centers. Student's t and chi-square tests
      evaluated the association between predetermined clinical and radiographic
      variables, including unknown time of onset, and outcome (discharge and follow-up
      National Institutes of Health Stroke Scale score and modified Rankin Scale [mRS]
      score) for LVOs treated after greater than 6 hours versus 6 hours or less from
      LKN. Multivariable logistic regression was used to determine the odds of good
      outcome (mRS score 0-2). RESULTS: A total of 113 patients were treated over 2
      years; 31 were treated at greater than 6 hours. Those who were treated at greater
      than 6 hours and experienced poor outcomes were more likely to have large-artery
      atherosclerosis (P = .033). There was no difference in outcome for patients
      outside the window with known (39.1%) versus unknown (60.9%) time of onset. mRS
      scores at discharge were higher among those outside the window (odds ratio 3.78;
      95% confidence interval 1.20-11.89) but not at follow-up. After multivariable
      regression, favorable collaterals alone were associated with a mRS score of 0-2.
      CONCLUSIONS: When imaging is favorable, the mRS score at follow-up is comparable
      regardless of time LKN. Functional outcomes appear to be driven most
      significantly by the presence of collaterals.

PMID- 29217365
TI  - Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after
      Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective
      Single-Center Study.
AB  - BACKGROUND: Clinical outcomes after successful endovascular therapy in patients
      with acute ischemic stroke are associated with several factors including onset-to
      reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS)
      score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time
      score, calculated as follows: [NIHSS score] * [onset-to-treatment time (h)] or
      [NIHSS score] * [ORT (h)], has been reported to predict clinical outcomes after
      intravenous recombinant tissue plasminogen activator therapy and endovascular
      therapy for acute stroke. The objective of the current study was to assess
      whether the combination of the ASPECTS and the ORT can predict the outcomes after
      endovascular therapy. METHODS: The charts of 117 consecutive ischemic stroke
      patients with successful reperfusion after endovascular therapy were
      retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and
      ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as
      follows: [11 - ASPECTS] * [ORT (h)]. RESULTS: Rates of good outcome for patients
      with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater
      than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and
      33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that
      the ASPECTS-time score (per category increase) was an independent predictor for
      better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P <
      .05). CONCLUSIONS: A lower ASPECTS-time score may predict better clinical
      outcomes after endovascular treatment.

PMID- 29217366
TI  - Initially Missed or Delayed Diagnosis of Subarachnoid Hemorrhage: A Nationwide
      Survey of Contributing Factors and Outcomes in Japan.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) remains a significant cause of
      mortality in Japan. The Japan Stroke Society set out to conduct a nationwide
      survey to identify contributing factors and outcomes of SAH misdiagnosis.
      METHODS: We initially surveyed 737 training institutes and 1259 departments in
      Japan between April 2012 and March 2014 for the presence of misdiagnosed SAH.
      Clinical information was then sought from respondents with a positive
      misdiagnosis. Information on 579 misdiagnosed cases was collected. RESULTS: Most
      initial misdiagnoses occurred in nonteaching hospitals (72%). Of those presenting
      with headache, 55% did not undergo a computed tomography (CT) scan. In addition,
      SAH was missed in the patients who underwent CT scans. The clinically diagnosed
      rerupture rate was 27%. Mortality among all cases was 11%. Institutes achieving a
      final diagnosis were staffed by neurologists or neurosurgeons. Multivariate
      logistic regression analysis indicated that age (>=65), consciousness level
      (Japan Coma Scale score at correct diagnosis), rerupture of an aneurysm, and no
      treatment by clipping or coiling were significantly associated with poor clinical
      outcome. CONCLUSIONS: The prognosis of misdiagnosis of SAH is severe.
      Neuroradiological assessment and correct diagnosis can prevent SAH misdiagnosis.
      When there is a possible diagnosis of SAH, consultation with a specialist is
      important.

PMID- 29217367
TI  - Response to the comments on "Direct quantitative measurement of the kinetics of
      HLA-specific antibody interactions with isolated HLA proteins".

PMID- 29217368
TI  - HLA-G, -A haplotypes in Amerindians (Ecuador): HLA-G*01:05N World distribution.
AB  - HLA-G and HLA-A frequencies have been analysed in Amerindians from Ecuador. HLA-G
      allele frequencies are found to be closer to those of other Amerindians (Mayas
      from Guatemala and Uros from Peru) and closer to European ones than to Far East
      Asians groups, particularly, regarding to HLA-G*01:04 allele. HLA-G/-A haplotypes
      have been calculated for the first time in Amerindians. It is remarkable that HLA
      G*01:05N "null" allele is found in a very low frequency (like in Amerindian Mayas
      and Uros) and is also found in haplotypes belonging to the HLA-A19 group of
      alleles (HLA-A*30, -A*31, -A*33). It was previously postulated that HLA-G*01:05N
      appeared in HLA-A*30/-B*13 haplotypes in Middle East Mediterraneans. It may be
      hypothesized that in Evolution, HLA-G*01:05N existed primarily in one of the HLA
      extant or extinct -A19 haplotype, whether this haplotype was placed in Middle
      East or other World areas, including America. However, the highest present day
      HLA-G*01:05N frequencies are found in Middle East Mediterraneans.

PMID- 29217370
TI  - A quality improvement initiative to increase Tdap (tetanus, diphtheria, acellular
      pertussis) vaccination coverage among direct health care providers at a
      children's hospital.
AB  - OBJECTIVES: Health care providers (HCP) are at high risk of acquiring and
      transmitting pertussis to susceptible family members, co-workers, and patients.
      Public health authorities recommend administering a single dose of Tdap (tetanus
      toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine to all
      adults, including HCP, to increase adult immunity to pertussis. We set a quality
      improvement goal to increase Tdap vaccination coverage among HCP who provided
      direct patient care at a children's hospital from 58% to 90% over 18 months.
      DESIGN: A multidisciplinary working group comprised of Occupational Health
      Program (OHP) staff and representatives of various medical services drew from a
      variety of qualitative methods and previous studies of vaccination programs in
      the healthcare system to understand barriers to Tdap vaccination within the
      institution and to develop interventions to increase vaccination rates.
      INTERVENTIONS: Interventions included changes to OHP processes, a general
      education campaign, improved access to vaccine, and personal engagement of HCP by
      task force members. RESULTS: Overall vaccination rates increased to 90% over 15
      months, a rate that has been sustained by systematically assessing new employees'
      vaccination status and vaccinating those without documentation of previous Tdap
      vaccination. CONCLUSIONS: Tdap vaccination coverage in our institution was
      significantly increased by an intensive, multipronged educational campaign, and
      by improving processes of screening and vaccination of HCP. The use of direct
      engagement of vaccine hesitant populations to increase vaccination rates warrants
      further study.

PMID- 29217369
TI  - Influence of the intestinal microbiota on the immunogenicity of oral rotavirus
      vaccine given to infants in south India.
AB  - Oral rotavirus vaccines have consistently proven to be less immunogenic among
      infants in developing countries. Discrepancies in the intestinal microbiota,
      including a greater burden of enteropathogens and an altered commensal community
      composition, may contribute to this trend by inhibiting the replication of
      vaccine viruses. To test this possibility, we performed a nested case-control
      study in Vellore, India, in which we compared the intestinal microbiota of
      infants who responded serologically or not after two doses of Rotarix delivered
      at 6 and 10 weeks of age as part of a clinical trial (CTRI/2012/05/002677). The
      prevalence of 40 bacterial, viral, and eukaryotic pathogen targets was assessed
      in pre-vaccination stool samples from 325 infants using singleplex real-time PCR
      on a Taqman array card (TAC). In a subset of 170 infants, we assessed bacterial
      microbiota composition by sequencing the 16S rRNA gene V4 region. Contrary to
      expectations, responders were more likely than non-responders to harbor >=1
      bacterial enteropathogen at dose 1 (26% [40/156] vs 13% [21/157] of infants with
      TAC results who completed the study per protocol; chi2, P = .006), although this
      was not apparent at dose 2 (24% [38/158] vs 23% [36/158]; P = .790). Rotavirus
      shedding after dose 1 was negatively correlated with the replication of co
      administered oral poliovirus vaccine (OPV). We observed no consistent differences
      in composition or diversity of the 16S bacterial microbiota according to
      serological response, although rotavirus shedding was associated with slightly
      more bacterial taxa pre-vaccination. Overall, our findings demonstrate an
      inhibitory effect of co-administered OPV on the first dose of Rotarix, consistent
      with previous studies, but in the context of OPV co-administration we did not
      find a strong association between other components of the intestinal microbiota
      at the time of vaccination and Rotarix immunogenicity.

PMID- 29217371
TI  - Reconstitution of the activity of RND efflux pumps: a "bottom-up" approach.
AB  - Efflux pumps are systems devoted to the extrusion of noxious compounds. In this
      review, we discuss the various strategies that have thus far been undertaken for
      the investigation of efflux pumps after reconstitution into liposomes. It is
      challenging to uncover mechanisms and dynamics of efflux pumps due to a number of
      characteristics: their function depends on the correct assembly of three
      components and they span two adjacent membranes whose lipid compositions are very
      different. In addition, efflux pumps are active transporters that need energy to
      work. We present possible lines of improvement for the study of such systems and
      provide insights into future goals and challenges of efflux pump reconstitution
      and transport.

PMID- 29217372
TI  - Acute peritoneal dialysis in neonatal intensive care unit: An 8-year experience
      of a referral hospital.
AB  - BACKGROUND: The aim of present study was to evaluate the indications,
      complications and outcomes of acute peritoneal dialysis (APD) in neonates at a
      referral university hospital during the previous 8 years. METHODS: This
      retrospective analysis included a total of 52 newborn infants who underwent APD
      in a neonatal intensive care unit between January 2008 and March 2016.
      Demographic, clinical, laboratory and microbiological data were extracted from
      patients' medical files. RESULTS: The primary causes for requiring APD were acute
      tubular necrosis (n = 36, 69.2%), inborn error of metabolism (n = 10, 19.2%),
      congenital nephrotic syndrome (n = 2, 3.9%), bilateral polycystic kidney (n = 2,
      3.9%), renal agenesis (n = 1, 1.9%), and obstructive uropathy (n = 1, 1.9%). The
      mean duration of APD was 8.7 +/- 15.87 days (range: 1-90 days). Procedural
      complications were mainly hyperglycemia (n = 16, 47.1%), dialysate leakage (n =
      7, 20.6%), peritonitis (n = 3, 8.8%), catheter obstruction (n = 3, 8.8%),
      bleeding at the time of catheter insertion (n = 2, 5.9%), catheter exit site
      infection (n = 2, 5.9%), and bowel perforation (n = 1 2.9%). There were 40 deaths
      (76.9%), mainly due to underlying causes. Ten of the 12 survivors showed full
      renal recovery, but mild chronic renal failure (n = 1) and proteinuria with
      hypertension were seen (n = 1) in each of remaining patients. CONCLUSION:
      Peritoneal dialysis is an effective route of renal replacement therapy in the
      neonatal period for management of metabolic disturbances as well as renal
      failure. Although major complications of the procedure are uncommon, these
      patients still have a high mortality rate due to serious nature of the underlying
      primary causes.

PMID- 29217373
TI  - Langerhans cell histiocytosis presenting like lichen planus in a 4-month-old
      infant.

PMID- 29217374
TI  - Modern contraceptive use, unmet need, and demand satisfied among women of
      reproductive age who are married or in a union in the focus countries of the
      Family Planning 2020 initiative: a systematic analysis using the Family Planning
      Estimation Tool.
AB  - BACKGROUND: The London Summit on Family Planning in 2012 inspired the Family
      Planning 2020 (FP2020) initiative and the 120*20 goal of having an additional 120
      million women and adolescent girls become users of modern contraceptives in 69 of
      the world's poorest countries by the year 2020. Working towards achieving 120 *
      20 is crucial for ultimately achieving the Sustainable Development Goals of
      universal access and satisfying demand for reproductive health. Thus, a
      performance assessment is required to determine countries' progress. METHODS: An
      updated version of the Family Planning Estimation Tool (FPET) was used to
      construct estimates and projections of the modern contraceptive prevalence rate
      (mCPR), unmet need for, and demand satisfied with modern methods of contraception
      among women of reproductive age who are married or in a union in the focus
      countries of the FP2020 initiative. We assessed current levels of family planning
      indicators and changes between 2012 and 2017. A counterfactual analysis was used
      to assess if recent levels of mCPR exceeded pre-FP2020 expectations. FINDINGS: In
      2017, the mCPR among women of reproductive age who are married or in a union in
      the FP2020 focus countries was 45.7% (95% uncertainty interval [UI] 42.4-49.1),
      unmet need for modern methods was 21.6% (19.7-23.9), and the demand satisfied
      with modern methods was 67.9% (64.4-71.1). Between 2012 and 2017 the number of
      women of reproductive age who are married or in a union who use modern methods
      increased by 28.8 million (95% UI 5.8-52.5). At the regional level, Asia has seen
      the mCPR among women of reproductive age who are married or in a union grow from
      51.0% (95% UI 48.5-53.4) to 51.8% (47.3-56.5) between 2012 and 2017, which is
      slow growth, particularly when compared with a change from 23.9% (22.9-25.0) to
      28.5% (26.8-30.2) across Africa. At the country level, based on a counterfactual
      analysis, we found that 61% of the countries that have made a commitment to
      FP2020 exceeded pre-FP2020 expectations for modern contraceptive use. Country
      success stories include rapid increases in Kenya, Mozambique, Malawi, Lesotho,
      Sierra Leone, Liberia, and Chad relative to what was expected in 2012.
      INTERPRETATION: Whereas the estimate of additional users up to 2017 for women of
      reproductive age who are married or in a union would suggest that the 120 * 20
      goal for all women is overly ambitious, the aggregate outcomes mask the diversity
      in progress at the country level. We identified countries with accelerated
      progress, that provide inspiration and guidance on how to increase the use of
      family planning and inform future efforts, especially in countries where progress
      has been poor. FUNDING: The Bill & Melinda Gates Foundation, through grant
      support to the University of Massachusetts Amherst and Avenir Health.

PMID- 29217375
TI  - Preliminary aggregate safety and immunogenicity results from three trials of a
      purified inactivated Zika virus vaccine candidate: phase 1, randomised, double
      blind, placebo-controlled clinical trials.
AB  - BACKGROUND: A safe, effective, and rapidly scalable vaccine against Zika virus
      infection is needed. We developed a purified formalin-inactivated Zika virus
      vaccine (ZPIV) candidate that showed protection in mice and non-human primates
      against viraemia after Zika virus challenge. Here we present the preliminary
      results in human beings. METHODS: We did three phase 1, placebo-controlled,
      double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three
      studies, healthy adults were randomly assigned by a computer-generated list to
      receive 5 MUg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army
      Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis
      University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center,
      Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The
      primary objective was safety and immunogenicity of the ZPIV candidate. We
      recorded adverse events and Zika virus envelope microneutralisation titres up to
      day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909,
      NCT02952833, and NCT02937233. FINDINGS: We enrolled 68 participants between Nov
      7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two
      injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild
      to moderate adverse events. The most frequent local effects were pain (n=40
      [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent
      systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and
      malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted
      (microneutralisation titre >=1:10), with peak geometric mean titres seen at day
      43 and exceeding protective thresholds seen in animal studies. INTERPRETATION:
      The ZPIV candidate was well tolerated and elicited robust neutralising antibody
      titres in healthy adults. FUNDING: Departments of the Army and Defense and
      National Institute of Allergy and Infectious Diseases.

PMID- 29217377
TI  - Tradition and innovation in development of a Zika vaccine.

PMID- 29217378
TI  - Serological evidence of Bovine herpesvirus-1, Bovine Viral Diarrhea virus and
      Schmallenberg virus infections in relation to reproductive disorders in dairy
      cattle in Ethiopia.
AB  - Reproductive disorders in dairy cattle have been noted to be common in urban and
      peri-urban dairy production system in Ethiopia. The available reports on the
      causes of these disorders, however, are not conclusive. A case-control study was
      designed to investigate the possible association of major reproductive disorders
      in dairy cattle with exposure status to bovine herpesvirus-1 (BHV-1), bovine
      viral diarrhea virus (BVDV) and Schmallenberg virus (SBV). Cows with history of
      abortion/stillbirth were considered as cases (n=204) while, those cows with no
      such history were taken as control (n=359). The serological screening tests used
      for all the three viruses were blocking enzyme linked immunosorbent assays (B
      ELISAs). Of the total 563 samples tested 58.4%, 43.8% and 32.9% were positive for
      SBV, BHV-1 and BVDV, respectively. Significant difference between cases and
      controls were noted for SBV (p=0.026) and BHV-1 exposures (p<0.001). The
      difference noted for BVDV serostatus was not significant (p>0.05). The highest
      proportion (28.9%) of concurrent exposures was noted for BHV-1 and SBV, followed
      by SBV and BVDV (21.5%) and BHV-1 and BVDV (20.2%). Evidence of exposures to all
      the three viruses were detected in 14.4% of the animals. However, significant
      difference between cases (39.7%) and controls (22.9%) among cattle with multiple
      sero-positivity was noted only for BHV-1 and SBV (p<0.001). Proportion of uterine
      infection (p=0.002) and fetal membrane retention (p=0.005) increased in BHV-1
      seropositive animals, while repeat breeding was common (p=0.034) among BVDV
      exposed ones. Seropositive animals to any of the three viruses were detected in
      all sampled areas and the proportion of cattle with BHV-1 and SBV exposure
      history had a higher risk to at least one type of the reproductive disorders
      mentioned compared to the corresponding sero-negative groups.

PMID- 29217376
TI  - Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates
      in healthy adults: randomised, open-label, phase 1 clinical trials.
AB  - BACKGROUND: The Zika virus epidemic and associated congenital infections have
      prompted rapid vaccine development. We assessed two new DNA vaccines expressing
      premembrane and envelope Zika virus structural proteins. METHODS: We did two
      phase 1, randomised, open-label trials involving healthy adult volunteers. The
      VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and
      Japanese encephalitis virus chimera), and the VRC 320, done in one centre,
      assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged
      18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly
      assigned 1:1 by a computer-generated randomisation schedule prepared by the study
      statistician. All participants received intramuscular injection of 4 mg vaccine.
      In VRC 319 participants were assigned to receive vaccinations via needle and
      syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20
      weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and
      8 weeks via single-dose needle and syringe injection in one deltoid or split-dose
      needle and syringe or needle-free injection with the Stratis device (Pharmajet,
      Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24
      months for the primary endpoint of safety, assessed as local and systemic
      reactogenicity in the 7 days after each vaccination and all adverse events in the
      28 days after each vaccination. The secondary endpoint in both trials was
      immunogenicity 4 weeks after last vaccination. These trials are registered with
      ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319
      enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants
      (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after
      one dose of vaccine, but were included in the safety analyses. Both vaccines were
      safe and well tolerated. All local and systemic symptoms were mild to moderate.
      In both studies, pain and tenderness at the injection site was the most frequent
      local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC
      320) and malaise and headache were the most frequent systemic symptoms (22 [27%]
      and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively,
      in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose
      vaccinations by needle-free injection had detectable positive antibody responses,
      and the geometric mean titre of 304 was the highest across all groups in both
      trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2
      efficacy testing. FUNDING: Intramural Research Program of the Vaccine Research
      Center, National Institute of Allergy and Infectious Diseases, National
      Institutes of Health.

PMID- 29217379
TI  - Major epidemiological factors associated with leptospirosis in Malaysia.
AB  - INTRODUCTION: Leptospirosis is a zoonotic disease caused by a diverse pathogenic
      leptospira species and serovars. The disease is transmitted directly following
      contact with infected urine and other body fluids or indirectly after contact
      with water or soil contaminated with infected urine. OBJECTIVES: While a wide
      range of domestic and wild animals are known to be reservoirs of the disease,
      occupation, international travel and recreation are beginning to assume a center
      stage in the transmission of the disease. The objective of this study is to
      review available literatures to determine the extent to which these
      aforementioned risk factors aid the transmission, increase incidence and outbreak
      of leptospirosis in Malaysia. STUDY DESIGN: The review was conducted based on
      prevalence, incidence, and outbreak cases of leptospirosis among human and
      susceptible animals predisposed to several of the risk factors identified in
      Malaysia. METHODS: Literature searchers and reviews were conducted based on
      articles published in citation index journals, Malaysian ministry of health
      reports, periodicals as well as reliable newspapers articles and online media
      platforms. In each case, the newspapers and online media reports were supported
      by press briefings by officials of the ministry of health and other agencies
      responsible. RESULTS: The disease is endemic in Malaysia, and this was attributed
      to the large number of reservoir animals, suitable humid and moist environment
      for proliferation as well as abundant forest resources. Over 30 different
      serovars have been detected in Malaysia in different domestic and wild animal
      species. This, in addition to the frequency of flooding which has increased in
      recent years, and has helped increase the risk of human exposure. Occupation,
      recreation, flooding and rodent population were all identified as an important
      source and cause of the disease within the study population. CONCLUSION: There is
      an urgent need for the government and other stakeholders to intensify efforts to
      control the spread of the disease, especially as it greatly affect human health
      and the tourism industry which is an important component of the Malaysian
      economy. The risk of infection can be minimized by creating awareness on the
      source and mode of transmission of the disease, including the use of protective
      clothing and avoiding swimming in contaminated waters. Moreover, improved
      diagnostics can also help reduce the suffering and mortalities that follow
      infection after exposure to infection source.

PMID- 29217380
TI  - Evaluation of rapid PfHRP-2/pLDH-based tests in diagnosing microscopy-confirmed
      falciparum malaria in Hodeidah governorate, Yemen.
AB  - Along with the determination of malaria infection rate among suspected patients
      attending hospitals in Hodeidah governorate, the present study evaluated the
      accuracy of Plasmodium falciparum histidine-rich protein-2 (PfHRP-2)/parasite
      specific lactate dehydrogenase (pLDH)-based rapid diagnostic test (RDT) for the
      diagnosis of microscopy-confirmed falciparum malaria. An overall malaria
      infection rate of 19.3% (57/295) among suspected patients attending hospitals was
      microscopically confirmed. The sensitivity of thin blood films for the detection
      of malaria parasites was 79.0% compared to thick films and was greatly affected
      by the parasite density, being 65.0% or less at parasite densities of <=1000
      parasites/MUl of blood. Compared to light microscopy, the present study revealed
      sensitivity levels of 100.0% (95% CI: 92.0-100.0) vs. 94.7% (95% CI: 84.2-98.6),
      specificity levels of 97.3% (95% CI: 89.8-99.5) vs. 100.0% (95% CI: 93.9-100.0),
      positive predictive values of 89.9% (95% CI: 88.3-99.0) vs. 100.0 (95% CI: 91.6
      100.0) and negative predictive values of 100.0% (95% CI: 93.9-100.0) vs. 98.7%
      (95% CI: 89.3-98.7) for the PfHRP-2 and pLDH components of SD BIOLINE(r) RDT,
      respectively, for falciparum malaria diagnosis. Therefore, the overall accuracy
      levels of the PfHRP-2 and pLDH components of the investigated RDT for the
      diagnosis of microscopy-confirmed falciparum malaria are 98.5% (95% CI: 94.6
      99.6) and 97.7% (95% CI: 93.5-99.2), respectively.

PMID- 29217381
TI  - Adiponectin levels and insulin resistance among patients with chronic hepatitis
      C.
AB  - Chronic hepatitis C virus (HCV) infection is associated with insulin resistance
      (IR), rapid disease progression, and decreased virological response to antiviral
      treatment. In addition, obesity is a risk factor for chronic hepatitis C
      evolution and is associated with IR. As adiponectin is an adipokine that is
      associated with obesity and IR, this study aimed to investigate serum levels of
      adiponectin among patients with HCV infection and IR. Thirty-three patients with
      untreated HCV infection underwent testing of serum adiponectin levels (capture
      ELISA) and were compared to 30 healthy subjects with similar body mass indexes
      (BMI). Data were also obtained for several homeostatic model assessment (HOMA)
      indexes: HOMA-IR, HOMA-beta, and HOMA-adiponectin. Patients with HCV infection
      had higher adiponectin levels, which predominantly were observed among women.
      Hyperadiponectinemia was not associated with high BMI. Patients with HCV
      infection had higher HOMA-IR and HOMA-beta values, although no difference was
      observed for HOMA-adiponectin. Patients with HCV infection and overweight/obese
      status had higher HOMA-IR values, although no association was observed for
      adiponectin levels. Hyperadiponectinemia and IR were not influenced by HCV load
      or liver fibrosis. The predictors of IR were BMI, glycemia, and serum levels of
      insulin and non-high-density lipoprotein cholesterol, but not adiponectin levels.
      Thus, patients with chronic hepatitis C have significant metabolic alterations
      (hyperadiponectinemia and high HOMA-IR values) that are independent of HCV
      viremia and liver fibrosis. Among these patients, HOMA-IR but not HOMA
      adiponectin was appropriate for diagnosing IR.

PMID- 29217382
TI  - New records of 13 species of black flies (Diptera: Simuliidae) from Myanmar.
AB  - A faunistic survey of black flies in Shan State, central Myanmar, was carried out
      in 2013. A total of 16 species were collected, of which 13 species are newly
      recorded from Myanmar. Among 13 newly recorded species, S. (S.) chiangmaiense
      Takaoka & Suzuki varied in the number of pupal gill filaments from eight to 10.
      This survey increases the number of species of black flies from Myanmar from 8 to
      23. They are classified in five subgenera of the genus Simulium: one in
      Asiosimulium, seven in Gomphostilbia, one in Montisimulium, two in Nevermannia
      and 12 in Simulium.

PMID- 29217383
TI  - Detection of Latino virus (Arenaviridae: Mammarenavirus) naturally infecting
      Calomys callidus.
AB  - Mammarenavirus species are associated with a specific rodent host species,
      although an increasing number of virus has been associated to more than one host,
      suggesting that co-evolution is less robust than initially thought. There are few
      eco-epidemiological studies of South America mammarenaviruses in non-endemic
      areas of Arenavirus Hemorrhagic Fever, affecting specially our current knowledge
      about animal reservoirs and virus range and host-virus relations. In Brazil,
      seven arenavirus species were described in seven different rodent species. Here
      in we describe a new rodent reservoir species in Brazil related to the previously
      described Latino mammarenavirus (LATV) MARU strain. Samples of 148 rodents from
      Mato Grosso state, Brazil were analyzed. Amplification of the glycoprotein
      precursor gene (GPC) was observed in six Calomys callidus rodents. According to
      phylogenetic inferences, is observed a well-supported monophyletic clade of LATV
      from C. callidus and other Clade C mammarenavirus. In addition, the phylogenetic
      relations of both genes showed a close relation between LATV MARU and Capao Seco
      strains, two distinct lineages. Additionally, the results obtained in this study
      point out to a change of scenario and in previously stabilized patterns in the
      dynamics of South American mammarenaviruses, showing that with more studies in
      AHF non-endemic or silent areas, more potential hosts for this virus will be
      discovered.

PMID- 29217384
TI  - Biocompatible sulfenamide and sulfonamide derivatives of metformin can exert
      beneficial effects on plasma haemostasis.
AB  - As the pharmacokinetic properties of metformin are unfavourable, several
      analogues and prodrugs have been synthesised to improve its bioavailability. The
      aim of this study was to assess the plasma stability of sulfenamide and
      sulfonamide derivatives of metformin and establish their effects on plasma
      haemostasis and integrity of red blood cells (RBCs). The overall haemostasis
      potential was evaluated spectrophotometrically by clot formation and lysis test
      (CL-test). PT (Prothrombin Time) and APTT (Activated Partial Tromboplastin Time)
      were used to evaluate the effects if the compounds on the extrinsic and intrinsic
      coagulation pathway. Haemolysis assay, microscopy and flow cytometry studies were
      conducted to determine the effect of the compounds on RBCs. Two sulfonamide and
      one sulfenamide derivatives of metformin were associated with a statistically
      significant decrease in the overall potential of clot formation and fibrinolysis
      (? CLAUC), suggesting that these compounds may exert beneficial effects regarding
      plasma haemostasis, which is frequently impaired in diabetic patients. p- and o
      Nitrobenzene sulfonamides contributed to the beneficial change in kinetic
      parameters of clot formation and fibrinolysis. o-Nitrobenzene sulfonamide
      significantly increased thrombin generation time (? TGt) and was also found to
      prolong both APTT and PT. All compounds did not exert any effects on the
      integrity of RBCs over the concentration range 0.006-0.6 MUmol/mL which
      constitutes the expected therapeutic concentration. In conclusion, sulfonamide
      derivatives of metformin present potentially beneficial properties in terms of
      plasma haemostasis which is frequently impaired in T2DM patients. Therefore,
      metformin sulfonamides may become a prototype for further design and synthesis of
      novel metformin analogues and prodrugs with improved pharmacokinetic properties.

PMID- 29217385
TI  - 4-methylesculetin, a coumarin derivative, ameliorates dextran sulfate sodium
      induced intestinal inflammation.
AB  - 4-methylesculetin is one of the coumarin derivatives with great anti-oxidant and
      anti-inflammatory activities. Recent studies have shown that 4-methylesculetin
      has a promising potentiality to treat inflammatory diseases, especially those
      related to reactive oxygen species, as inflammatory bowel disease. Based on this,
      the present study aims to investigate the intestinal anti-inflammatory activity
      of 4-methylesculetin in dextran sulfate sodium (DSS) model. For this purpose,
      mice received DSS 5% for 5 days followed by 2 days of filtered tap water. Treated
      groups received orally 5 or 25 mg/kg of 4-methylesculetin daily since the first
      day. Macroscopic, microscopic and biochemical parameters were evaluated. 4
      methylesculetin (25 mg/kg) improved microscopic parameters, decreased MPO
      activity, reduced the colonic levels of IL-6 and counteracted GSH depletion when
      compared with DSS-control group. Our results show the intestinal anti
      inflammatory activity of 4-methylesculetin in DSS model, which is related to its
      antioxidant and anti-inflammatory properties. This way, 4-methylesculetin, is a
      new potential compound for treatment of both types of IBD.

PMID- 29217386
TI  - Early worsening of diabetic retinopathy after rapid improvement of blood glucose
      control in patients with diabetes.
AB  - AIM: To review the frequency, importance of and risk factors for "early worsening
      of diabetic retinopathy" (EWDR) after rapid improvement of blood glucose in
      patients with diabetes. METHODS: This was a systematic review of key references
      (PubMed 1980-2016) and the current international recommendations for the above
      mentioned topics. RESULTS: EWDR has been described during intensive treatment
      (IT) in patients with uncontrolled type 1 or 2 diabetes, and after pancreas
      transplantation or bariatric surgery. EWDR arises in 10-20% of patients within 3
      6 months after abrupt improvement of glucose control, and in nearly two times
      that proportion in patients with advanced baseline diabetic retinopathy (DR).
      While EWDR is often transient and predominantly driven by the development of
      cotton-wool spots and intraretinal microvascular abnormalities in patients with
      no or minimal DR, it can lead to irreversible retinal damage in patients with
      advanced DR before IT. Its identified risk factors include higher baseline levels
      and larger magnitudes of reduction of HbA1c, longer diabetes durations and
      previous severity of DR. CONCLUSION: Intensive diabetes treatment inducing a
      rapid fall in glucose should prompt vigilance and caution, particularly in
      patients with long-term and uncontrolled diabetes and DR prior to IT. Careful
      retinal examination should be performed in all patients before initiating IT;
      however, in patients with severe non-proliferative or proliferative DR,
      panretinal photocoagulation therapy should be performed promptly. During the year
      following IT, quarterly eye monitoring is required in patients at high risk of
      EWDR (long-term uncontrolled diabetes, previous advanced DR), whereas follow-up
      every 6 months can be applied in patients with short-term diabetes and no/minimal
      DR before IT. To date, there is no evidence that controlling the speed or
      magnitude of HbA1c decreases will reduce the risk of EWDR in patients with
      diabetes.

PMID- 29217387
TI  - Individualised versus standard duration of elastic compression therapy for
      prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised,
      single-blind, allocation-concealed, non-inferiority trial.
AB  - BACKGROUND: Therapy with elastic compression stockings has been the cornerstone
      for prevention of post-thrombotic syndrome for decades in patients after acute
      deep venous thrombosis. It is uncertain who benefits most from therapy, and what
      the optimum duration of therapy should be. We therefore aimed to assess the
      safety and efficacy of individualised duration of compression therapy versus the
      standard duration of 24 months following an initial treatment period of 6 months.
      METHODS: We did a multicentre, randomised, single-blind, allocation-concealed,
      non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We
      randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the
      leg and without pre-existent venous insufficiency (Clinical Etiological
      Anatomical and Pathophysiological score <C3) to receive either individualised
      duration of elastic compression therapy or standard duration of therapy for 24
      months following an initial treatment period of 6 months. Randomisation was done
      with a web-based automatic randomisation programme (TENALEA) and a random block
      size (2-12), and was stratified by centre, age, and body-mass index. In the
      initial phase, compression was applied within 24 h of diagnosis according to
      three prespecified protocols. All patients received elastic compression stockings
      (30-40 mm Hg) for 6 months, and were instructed to wear them every day during
      ambulant hours. Thereafter treatment was tailored on the basis of clinical signs
      and symptoms scored according to the Villalta post-thrombotic syndrome scale;
      patients assigned to individualised therapy with two consecutive Villalta scores
      of 4 or less were instructed to stop using the stockings. Patients were followed
      up for 2 years and assessed at five clinic visits at study inclusion, and 3, 6,
      12, and 24 months after diagnosis (stocking allocation was not revealed to the
      assessors). The primary outcome was the proportion of patients with post
      thrombotic syndrome at 24 months diagnosed according to original Villalta
      criteria (a score of >=5 on two consecutive occasions at least 3 months apart)
      assessed by intention to treat. The predefined non-inferiority margin for the
      difference in success rates was set at 7.5%. This study has been completed and is
      registered with ClinicalTrials.gov, number NCT01429714. FINDINGS: Between March
      22, 2011, and July 1, 2015, we enrolled 865 patients and randomly assigned 437 to
      individualised duration compression stockings and 428 to standard duration. 283
      (66%) of 432 patients in the intervention group were advised before 24 months to
      stop wearing elastic compression stockings (236 [55%] of 432 patients after 6
      months, and 47 [11%] of 432 at 12 months). Post-thrombotic syndrome occurred in
      125 (29%) of 432 patients receiving individualised duration of therapy and in 118
      (28%) of 424 receiving standard duration of therapy (odds ratio for difference
      1.06, 95% CI 0.78 to 1.44). The absolute difference was 1.1% (95% CI -5.2 to
      7.3), thus meeting the non-inferiority margin. 24 patients died, 17 (4%) in the
      individualised treatment group and seven (2%) in the standard duration group, but
      no deaths were related to treatment. No serious adverse events related to the
      intervention occurred. INTERPRETATION: Individualised therapy with elastic
      compression stockings for the prevention of post-thrombotic syndrome was non
      inferior to standard duration of therapy of 24 months. Individualising the
      duration is effective and could shorten the length of therapy needed, potentially
      enhancing patients' wellbeing. FUNDING: ZonMw (Netherlands).

PMID- 29217388
TI  - Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and
      Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation
      Recipients.
AB  - The optimal viral load threshold at which to initiate preemptive cytomegalovirus
      (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to
      be defined. In an effort to address this question, we conducted a retrospective
      study of 174 allogeneic HCT recipients who underwent transplantation at a single
      center between August 2012 and April 2016. During this period, preemptive therapy
      was initiated at the discretion of the treating clinician. A total of 109
      patients (63%) developed CMV viremia. The median time to reactivation was 17 days
      (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia >=150 IU/mL was
      strongly associated with a reduced probability of spontaneous clearance (relative
      risk, .16; 95% confidence interval, .1-.27), independent of established clinical
      risk factors, including CMV donor serostatus, exposure to antithymocyte globulin,
      and underlying lymphoid malignancy. The median time to clearance of viremia was
      significantly shorter in those who started therapy at CMV <350 IU/mL (19 days;
      IQR, 11-35 days) compared with those who started antiviral therapy at higher
      viremia thresholds (33 days; IQR, 21-42 days; P = .02). The occurrence of
      treatment-associated cytopenias was frequent but similar in patients who started
      preemptive therapy at CMV <350 IU/mL and those who started at CMV >350 IU/mL (44%
      versus 57%; P = .42). Unresolved CMV viremia by treatment day 35 was associated
      with increased risk of therapeutic failure (32% versus 0%; P = .001). Achieving
      eradication of CMV viremia by treatment day 35 was associated with a 74%
      reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26;
      95% confidence interval [CI], .1-.8; P = .02), whereas therapeutic failure was
      associated with a significant increase in the probability of 1-year NRM (adjusted
      HR, 26; 95% CI, 8-87; P <.0001). We conclude that among allogeneic HCT patients,
      a peak CMV viremia >=150 IU/mL is associated with a >80% reduction in the
      probability of spontaneous clearance independent of ATG administration, CMV donor
      serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive
      therapy. Delaying initiation of therapy until a CMV value >=350 IU/mL is
      associated with more protracted CMV viremia, and unresolved viremia by treatment
      day 35 is associated with a significant increase in NRM.

PMID- 29217389
TI  - Competencies for engaging high-needs patients in primary care.
AB  - BACKGROUND: Patients who heavily utilize hospitals and emergency departments
      frequently have complex needs requiring services spanning medical, behavioral,
      and social service sectors. This study identifies essential competencies for
      caring for high-needs patients and highlights their importance to primary care
      delivery. METHODS: Transcripts of in-depth interviews with 30 clinical and
      administrative staff at 23 complex care programs across the United States were
      analyzed using standard qualitative techniques. Selected programs had several
      years of experience in serving patients with multiple chronic conditions, serious
      mental illness, substance use disorders, severe poverty, and homelessness. These
      programs exemplified diverse models (assertive community treatment, housing
      first, behavioral health, high utilizer), and all of them shared the common
      element of integrating primary care into their services. RESULTS: Competencies,
      including those known and taught in other fields, have distinctive application to
      informing delivery of high quality primary care to populations with complex
      needs, including: motivational interviewing for establishing patients' priorities
      and helping them improve their health on their own terms; trauma-informed care
      for modifying primary care procedures to mitigate the ill-effects of prior trauma
      prevalent in this population; and harm reduction for altering medical regimens to
      accommodate constraints on what patients are able or willing to do. Other
      capabilities, cultivated by these programs, include empathizing with patients,
      promoted by exposure to simulations of patient experiences (e.g., hearing
      voices); as well as withholding judgment and counteracting patient passivity to
      foster open discussion of treatment plans. CONCLUSIONS: Absence of deliberate
      attention to equipping providers with specific competencies for caring for high
      needs patients may contribute to lack of patient engagement and sub-optimal
      outcomes, ultimately undermining the success of programs serving these
      populations.

PMID- 29217390
TI  - Food and beverage TV advertising to young children: Measuring exposure and
      potential impact.
AB  - Children of all ages are vulnerable to influence from exposure to unhealthy food
      advertisements, but experts raise additional concerns about children under 6 due
      to their more limited cognitive abilities. Most companies in the U.S. Children's
      Food and Beverage Advertising Initiative (CFBAI) industry self-regulatory program
      pledge to not direct any advertising to children under 6. However, young children
      also watch programming primarily directed to older children and thus may view
      food-related advertising despite companies' pledges. Research is required to
      understand the amount and potential impact of this exposure on preschool-age
      children. Study 1 uses Nielsen advertising exposure data to compare preschoolers'
      (2-5 years) and older children's (6-11 years) exposure to food advertising in
      2015. Preschoolers viewed on average 3.2 food ads daily on children's
      programming, just 6% fewer compared to 6- to 11-year-olds; over 60% were placed
      by CFBAI-participating companies. Study 2 exposed young children (N = 49) in a
      child-care setting to child-directed food ads, measured their attitudes about the
      ads and advertised brands, and compared responses by 4- to 5-year-olds and 6- to
      7-year olds. Most children indicated that they liked the child-directed ads, with
      media experience associated with greater liking for both age groups. Ad liking
      and previous consumption independently predicted brand liking for both age
      groups, although previous consumption was a stronger predictor for older
      children. Despite pledges by food companies to not direct advertising to children
      under age 6, preschoolers continue to view advertisements placed by these
      companies daily, including on children's programming. This advertising likely
      increases children's preferences for nutritionally poor advertised brands. Food
      companies and media companies airing children's programming should do more to
      protect young children from advertising that takes advantage of their
      vulnerabilities.

PMID- 29217391
TI  - Percutaneous Transvenous Mitral Valve-in-Valve Implantation Using Commercially
      Available Transcatheter Valve. First Australian Experience.
AB  - In patients with a degenerative mitral bioprosthesis and prohibitive surgical
      risk there is emerging evidence for the feasibility of valve-in-valve procedures
      via a percutaneous transvenous transseptal approach. This paper describes the
      first time this procedure has been performed in Australia.

PMID- 29217392
TI  - Influence of traffic on build-up of polycyclic aromatic hydrocarbons on urban
      road surfaces: A Bayesian network modelling approach.
AB  - Due to their carcinogenic effects, Polycyclic Aromatic Hydrocarbons (PAHs)
      deposited on urban surfaces are a major concern in the context of stormwater
      pollution. However, the design of effective pollution mitigation strategies is
      challenging due to the lack of reliability in stormwater quality modelling
      outcomes. Current modelling approaches do not adequately replicate the
      interdependencies between pollutant processes and their influential factors.
      Using Bayesian Network modelling, this research study characterised the influence
      of vehicular traffic on the build-up of the sixteen US EPA classified priority
      PAHs. The predictive analysis was conditional on the structure of the proposed
      BN, which can be further improved by including more variables. This novel
      modelling approach facilitated the characterisation of the influence of traffic
      as a source of origin and also as a key factor that influences the re
      distribution of PAHs, with positive or negative relationship between traffic
      volume and PAH build-up. It was evident that the re-distribution of particle
      bound PAHs is determined by the particle size rather than the chemical
      characteristics such as volatility. Moreover, compared to commercial and
      residential land uses, mostly industrial land use contributes to the PAHs load
      released to the environment. Carcinogenic PAHs in industrial areas are likely to
      be associated with finer particles, while PAHs, which are not classified as human
      carcinogens, are likely to be found in the coarser particle fraction.

PMID- 29217393
TI  - Acetabular Revision Using Trabecular Metal Augments for Paprosky Type 3 Defects.
AB  - BACKGROUND: Trabecular Metal (TM) augments are one option when reconstructing
      bone loss during acetabular side revision surgery. METHODS: We studied 38
      consecutive patients with Paprosky type 3 defects that were revised using a TM
      shell and one or more augments over a 6-year period. There were 29 Paprosky type
      3A defects and 9 Paprosky type 3B defects. The mean age of the patients at the
      time of surgery was 68.2 years (range 48-84). The mean length of follow-up was 36
      months (range 18-74). RESULTS: The mean preoperative short form 12 health survey
      improved from 27.7 before operation to 30.1 at the time of final follow-up (P =
      .001). The mean Western Ontario and McMaster Universities Osteoarthritis Index
      score improved from 53 preoperatively to a mean of 78.8 at final follow-up (P <
      .0001). There was evidence of radiographic loosening in 7 of the cup-augment
      constructs. One patient developed a deep infection requiring re-revision. Two
      patients required revision for aseptic loosening. CONCLUSION: The use of TM in
      complex acetabular reconstruction is associated with good outcome in the short to
      medium term.

PMID- 29217394
TI  - The use of end-tidal carbon dioxide (ETCO2) measurement to guide management of
      cardiac arrest: A systematic review.
AB  - AIMS: To identify whether any level of end-tidal carbon dioxide (ETCO2) measured
      during cardiopulmonary resuscitation (CPR) correlates with return of spontaneous
      circulation (ROSC) or survival in adults experiencing cardiac arrest in any
      setting. METHODS: Systematic review. We included randomized controlled trials,
      cohort studies, and case-control studies of adult cardiac arrest in any setting
      that reported specific (rather than pooled) ETCO2 values and attempted to
      correlate those values with prognosis. Full-text articles were searched on
      EmBASE, MEDLINE, and Cochrane Database. The Grades of Recommendation, Assessment,
      Development and Evaluation (GRADE) guidelines were followed, assigning levels of
      quality to all evidence used in the meta-analysis. RESULTS: Seventeen
      observational studies, describing a total of 6198 patients, were included in the
      qualitative synthesis, and five studies were included in the meta-analysis. The
      available studies provided consistent but low-quality evidence that ETCO2
      measurements >=10mmHg, obtained at various time points during CPR, are
      substantially related to ROSC. Additional cut-off values were also found. Initial
      ETCO2 or 20-min ETCO2>20mmHg appears to be a better predictor of ROSC than the
      10mmHg cut off value. A ETCO2<10mmHg after 20min of CPR is associated with a 0.5%
      likelihood of ROSC. CONCLUSIONS: Based upon existing evidence, ETCO2 levels do
      seem to provide limited prognostic information for patients who have experienced
      cardiac arrest. Given the many potential confounders that can influence initial
      ETCO2 levels, extreme or trending values may be more useful than static mid-range
      levels. Additional well-designed studies are needed to define optimal timing for
      the measurement of ETCO2 for prognostic purposes.

PMID- 29217395
TI  - Out-of-hospital cardiac arrest: Probability of bystander defibrillation relative
      to distance to nearest automated external defibrillator.
AB  - AIMS: Despite wide dissemination of automated external defibrillators (AEDs),
      bystander defibrillation rates remain low. We aimed to investigate how route
      distance to the nearest accessible AED was associated with probability of
      bystander defibrillation in public and residential locations. METHODS: We used
      data from the nationwide Danish Cardiac Arrest Registry and the Danish AED
      Network to identify out-of-hospital cardiac arrests and route distances to
      nearest accessible registered AED during 2008-2013. The association between route
      distance and bystander defibrillation was described using restricted cubic spline
      logistic regression. RESULTS: We included 6971 out-of-hospital cardiac arrest
      cases. The proportion of arrests according to distance in meters (<=100, 101-200,
      >200) to the nearest accessible AED was: 4.6% (n=320), 5.3% (n=370), and 90.1%
      (n=6281), respectively. For cardiac arrests in public locations, the probability
      of bystander defibrillation at 0, 100 and 200m from the nearest AED was 35.7%
      (95% confidence interval 28.0%-43.5%), 21.3% (95% confidence interval 17.4%
      25.2%), and 13.7% (95% confidence interval 10.1%-16.8%), respectively. The
      corresponding numbers for cardiac arrests in residential locations were 7.0% (95%
      confidence interval -2.1%-16.1%), 1.5% (95% confidence interval 0.002%-2.8%), and
      0.9% (95% confidence interval 0.0005%-1.7%), respectively. CONCLUSIONS: In public
      locations, the probability of bystander defibrillation decreased rapidly within
      the first 100m route distance from cardiac arrest to nearest accessible AED
      whereas the probability of bystander defibrillation was low for all distances in
      residential areas.

PMID- 29217396
TI  - A 2018 Horizon Scan of Emerging Issues for Global Conservation and Biological
      Diversity.
AB  - This is our ninth annual horizon scan to identify emerging issues that we believe
      could affect global biological diversity, natural capital and ecosystem services,
      and conservation efforts. Our diverse and international team, with expertise in
      horizon scanning, science communication, as well as conservation science,
      practice, and policy, reviewed 117 potential issues. We identified the 15 that
      may have the greatest positive or negative effects but are not yet well
      recognised by the global conservation community. Themes among these topics
      include new mechanisms driving the emergence and geographic expansion of
      diseases, innovative biotechnologies, reassessments of global change, and the
      development of strategic infrastructure to facilitate global economic priorities.

PMID- 29217397
TI  - [Development of methods to evaluate nephrological screening and support measures,
      and lessons learned from the Styrian nephrological screening program
      "niere.schutzen"].
AB  - Throughout the world, the incidence and prevalence of patients with chronic
      kidney disease have been steadily rising. In 2016, the Styrian nephrology
      awareness program "niere.schutzen" ("Kidney Protection") was launched to early
      identify patients with renal insufficiency. The aim of this study was to search
      for existing international nephrological screening and support programs in order
      to identify possible evaluation parameters and concepts for niere.schutzen. A
      search in MEDLINE(r) revealed five relevant international programs from four
      countries. These differed from one another with respect to the population to be
      screened, the screening method and the support measures. All the programs
      involved the transparent documentation of patient data, and allowed for disease
      monitoring, as well as the impact of specific measures on assessed parameters and
      variables (laboratory data, participation rates) to be determined. Depending on
      the data sources employed and the availability and comprehensiveness of
      additional documentation, three evaluation methods of different informative value
      were developed. The first method requires no participant labelling, while the
      second and third methods require the participants to be assigned to a particular
      program. With the third method, the documentation also needs to be conducted in
      line with a disease management program. Considering that the speedy
      implementation of the niere.schutzen program is desired for political reasons,
      the only practical method is the first one as it does not entail patient
      documentation and only involves the evaluation of process parameters.

PMID- 29217398
TI  - Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy
      sufficient to increase surgery-free and distant metastases-free survival in
      baseline cT3 rectal cancer?
AB  - : Patients with cT3 rectal cancer are less likely to develop complete response to
      neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic
      relapse. In this setting, radiation (RT) dose-escalation and consolidation
      chemotherapy in "extended" nCRT regimens have been suggested to improve primary
      tumor response and decrease the risks of systemic recurrences. For these reasons
      we compared surgery-free and distant-metastases free survival among cT3 patients
      undergoing standard or extended nCRT. METHODS: Patients with distal and non
      metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed.
      Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy)
      were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based
      chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients
      with complete clinical response (cCR) underwent organ-preservation strategy
      (Watch & Wait). Patients were referred to salvage surgery in the event of local
      recurrence during follow-up. Cox's logistic regression was performed to identify
      independent features associated with improved surgery-free survival after cCR and
      distant-metastases-free survival. RESULTS: 155 patients underwent standard and 66
      patients extended CRT. Patients undergoing extended CRT were more likely to
      harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p <
      0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed
      that the type of nCRT regimen was not independently associated with distinct
      surgery-free survival after cCR or distant-metastases-free survival (p > 0.05).
      CONCLUSIONS: Dose-escalation and consolidation chemotherapy are insufficient to
      increase long-term surgery-free survival among cT3 rectal cancer patients and
      provides no advantage in distant metastases-free survival.

PMID- 29217400
TI  - Biocatalytic production of (S)-2-aminobutanamide by a novel d-aminopeptidase from
      Brucella sp. with high activity and enantioselectivity.
AB  - As the important chiral building block of levetiracetam, the synthesis of (S)-2
      aminobutanamide has attracted a great deal of attention. The d-aminopeptidase
      catalyzed kinetic resolution of 2-aminobutanamide was demonstrated as an
      effective strategy for (S)-2-aminobutanamide production. In this study, a novel d
      aminopeptidase from Brucella sp. (Bs-Dap) was screened and systematically
      characterized. The enzyme exhibited maximum activity at 45 degrees C, pH 8.0 and
      it showed relatively low Km value toward 2-aminobutanamide, indicating its high
      affinity to the substrate. Kinetic resolution of 300g/L 2-aminobutanamide by
      recombinant Escherichia coli whole cells (4g/L wet cell weight) resulted in 50%
      conversion and >99% e.e. within 80min. The catalytic properties of Bs-Dap
      demonstrated its great potential for industrial production of (S)-2
      aminobutanamide.

PMID- 29217399
TI  - Feasibility of breast MRI after sentinel procedure for breast cancer with
      superparamagnetic tracers.
AB  - RATIONALE: The gold standard for detection of axillary sentinel lymph nodes uses
      injection of a radioisotope (99Tc Nanocoll). As an alternative to this method, a
      magnetometer detecting the superparamagnetic tracer Sienna+(r) can be applied for
      detection of sentinel lymph nodes. The goal of this study was to determine
      whether interpretation of breast MRI is impaired by Sienna+(r) tracer residues in
      the operated breast and axillary lymph nodes after a sentinel procedure using
      this tracer. PATIENTS AND METHODS: 34 patients who received the Sienna+(r) tracer
      for marking the sentinel node were invited to undergo a follow-up breast MRI.
      Native MR images were obtained from breast and axilla. The breast MRIs were
      evaluated by two independent breast radiologists for Sienna+(r) tracer related
      artefacts and for the degree of impairment of the MR imaging. RESULTS: 24 of the
      34 invited patients took part in this study. The mean time since injection of
      Sienna+(r) was 42 months (40.6-45.4 months). Two patients had bilateral surgery
      with injections in both breasts, leading to a total of 26 separate cases. One
      case had to be excluded due to breathing artefacts. In 10 cases (40%), impaired
      imaging was found. In three cases (12%), the MRI scan reading was impossible due
      to Sienna+(r) tracer residues, the other 12 cases (48%) showed no restriction. In
      the subgroup of patients treated with breast conserving surgery, tracer residue
      artefacts were found in 13 of 17 patients (76.5%). CONCLUSION: To our knowledge,
      in this study for the first time MR feasibility after Sienna injection was
      investigated. Sienna+(r) impaired breast MRI after a mean follow-up time of 42
      months in half of the cases. Further research is needed to investigate time and
      field-strength dependency of tracer detectability as well as the diagnostic
      impact of these artifacts on contrast-enhanced imaging in a clinical setting.

PMID- 29217401
TI  - Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene
      expression on the risk of schizophrenia.
AB  - Converging evidence suggests important implications of immuno-inflammatory
      pathway in the risk and progression of schizophrenia. Prenatal infection
      resulting in maternal immune activation and developmental neuroinflammation
      reportedly increases the risk of schizophrenia in the offspring by generating pro
      inflammatory cytokines including IL-6. However, it is not known how prenatal
      infection can induce immuno-inflammatory responses despite the presence of immuno
      inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the
      present study was aimed at examining the correlation between 14 bp
      Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in
      schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR
      amplification/direct sequencing and IL-6 gene expression was quantified by using
      real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We
      observed significantly low IL6 gene expression in the peripheral mononuclear
      cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the
      controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G
      14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004)
      than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence
      of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could
      attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it
      can be assumed that HLA-G and cytokine interactions might play an important role
      in the immunological underpinnings of schizophrenia.

PMID- 29217402
TI  - Inflammatory profile analysis reveals differences in cytokine expression between
      smokers, moist snuff users, and dual users compared to non-tobacco consumers.
AB  - OBJECTIVE AND DESIGN: The aim of this study is to investigate the inflammatory
      alterations due to the use of smokeless tobacco and dual use of smokeless tobacco
      and cigarettes, relative to smoking. SUBJECTS: Plasma and saliva samples were
      collected from healthy smokers (SMK-100 subjects), moist snuff users (MSC-89
      subjects), the dual users (DUSMK-49 subjects), and non-tobacco consumers (NTC-99
      subjects) from two cross-sectional studies. METHODS: Luminex Human
      InflammationMAP(r) 1.0 panel, a multiplex immunoassay. RESULTS: SMK and DUSMK
      exhibited larger number of alterations in the expression of inflammatory analytes
      compared to NTC. Eight analytes were significantly elevated (p <= .05) within
      plasma samples of SMK compared to NTC, while one 1 analyte was elevated between
      the MSC and NTC groups. DUSMK exhibited different levels of 11 analytes, relative
      to NTC. MSC displayed fewer alterations in inflammatory protein expression
      compared to smoker groups, and the inflammatory profile of MSC resembles NTC.
      Five analytes (ICAM-1, VEGF, MMP-9, ferritin and fibrinogen) emerged as potential
      biomarkers distinguishing tobacco consumers (p < .02). CONCLUSIONS: We identified
      a set of five proteins as potential biomarkers that can inform of inflammation
      status due to tobacco usage. Our findings contribute a better understanding of
      how the use of different tobacco products contributes to inflammation.

PMID- 29217403
TI  - Transcriptome analysis reveals a positive role for nerve growth factor in retinol
      metabolism in primary rat hepatocytes.
AB  - Up-regulation of nerve growth factor (NGF) in parenchymal hepatocytes with
      cholestatic injury has been previously demonstrated to exert hepatoprotective
      effects in an autocrine manner; however, the overall impact of NGF up-regulation
      remains elusive. This study aimed to profile the effects of exogenous NGF on
      cultured primary rat hepatocytes using transcriptome analysis. Total RNA was
      isolated from hepatocytes with and without 24 h of NGF exposure, and subjected to
      RNA enrichment by PCR and RNA sequencing procedures. Comparison of transcriptome
      profiles between control and NGF-stimulated hepatocytes demonstrated that NGF
      significantly up-regulated 10 genes and down-regulated 23 genes in hepatocytes.
      Subsequent KEGG pathway enrichment analysis indicated that NGF significantly
      affected the retinol metabolism pathway via increased retinol dehydrogenase 16
      (RDH16) expression. In a mouse model of bile duct ligation-induced cholestatic
      liver injury, NGF supplementation significantly enhanced RDH16 expression,
      whereas administration of anti-NGF neutralizing antibodies prominently decreased
      RDH16 expression in cholestatic livers, supporting the positive role of NGF in
      the regulation of RDH16 in diseased livers. In vitro study further demonstrated
      that NGF triggered de novo synthesis of RDH16 in primary rat hepatocytes, mainly
      through an NF-kappaB signaling pathway. In conclusion, this study demonstrates
      the up-regulation of RDH16 by NGF in cultured rat hepatocytes and mouse
      cholestatic livers, and provides novel insights on the mechanistic role of NGF in
      the retinol metabolism of livers.

PMID- 29217405
TI  - A novel perspective to calibrate temporal delays in cerebrovascular reactivity
      using hypercapnic and hyperoxic respiratory challenges.
AB  - Redistribution of blood flow across different brain regions, arising from the
      vasoactive nature of hypercapnia, can introduce errors when examining
      cerebrovascular reactivity (CVR) response delays. In this study, we propose a
      novel analysis method to characterize hemodynamic delays in the blood oxygen
      level dependent (BOLD) response to hypercapnia, and hyperoxia, as a way to
      provide insight into transient differences in vascular reactivity between
      cortical regions, and across tissue depths. A pseudo-continuous arterial spin
      labeling sequence was used to acquire BOLD and cerebral blood flow simultaneously
      in 19 healthy adults (12 F; 20 +/- 2 years) during boxcar CO2 and O2 gas
      inhalation paradigms. Despite showing distinct differences in hypercapnia-induced
      response delay times (P < 0.05; Bonferroni corrected), grey matter regions showed
      homogenous hemodynamic latencies (P > 0.05) once calibrated for bolus arrival
      time derived using non-vasoactive hyperoxic gas challenges. Longer hypercapnic
      temporal delays were observed as the depth of the white matter tissue increased,
      although no significant differences in response lag were found during hyperoxia
      across tissue depth, or between grey and white matter. Furthermore, calibration
      of hypercapnic delays using hyperoxia revealed that deeper white matter layers
      may be more prone to dynamic redistribution of blood flow, which introduces
      response lag times ranging between 1 and 3 s in healthy subjects. These findings
      suggest that the combination of hypercapnic and hyperoxic gas-inhalation MRI can
      be used to distinguish between differences in CVR that arise as a result of
      delayed stimulus arrival time (due to the local architecture of the
      cerebrovasculature), or preferential blood flow distribution. Calibrated response
      delays to hypercapnia provide important insights into cerebrovascular physiology,
      and may be used to correct response delays associated with vascular impairment.

PMID- 29217406
TI  - LncRNA SNHG1 promotes alpha-synuclein aggregation and toxicity by targeting miR
      15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells.
AB  - Numerous long non-coding RNAs (lncRNAs) have been identified as aberrantly
      expressed in Parkinson's disease (PD). However, limited knowledge is available
      concerning the roles of dysregulated lncRNAs and the underlying molecular
      regulatory mechanism in the pathological process of PD. In this study, we found
      that lncRNA small nucleolar RNA host gene 1 (SNHG1) and seven in absentia homolog
      1 (SIAH1) were upregulated, but microRNA-15b-5p (miR-15b-5p) was downregulated in
      SH-SY5Y cells pretreated with MPP+, as well as in MPTP-induced mouse model of PD.
      Overexpression of SIAH1 enhanced cellular toxicity of alpha-synuclein in SH-SY5Y
      cells, as indicated by the reduction of cell viability and elevation of LDH
      release. The percentage of alpha-synuclein aggregate-positive cells and the
      number of alpha-synuclein aggregates per cell were increased in SH-SY5Y cells
      transfected with pcDNA-SIAH1, while decreased after transfection with short
      interfering RNA specific for SIAH1 (si-SIAH1). Bioinformatics and luciferase
      reporter assay revealed that SIAH1 was a direct target of miR-15b-5p. We also
      found that SNHG1 could directly bind to miR-15-5p and repress miR-15-5p
      expression. Upregulation of miR-15b-5p alleviated alpha-synuclein aggregation and
      apoptosis by targeting SIAH1 in SH-SY5Y cells overexpressing alpha-synuclein.
      Overexpression of SNHG1 enhanced, whereas SNHG1 knockdown inhibited alpha
      synuclein aggregation and alpha-synuclein-induced apoptosis. Moreover, the
      neuroprotective effect of si-SNHG1 was abrogated by downregulation of miR-15b-5p.
      In summary, our data suggest that SNHG1, as a pathogenic factor, promotes alpha
      synuclein aggregation and toxicity by targeting the miR-15b-5p/SIAH1 axis,
      contributing to a better understanding of the mechanisms of Lewy body formation
      and loss of dopaminergic neurons in PD.

PMID- 29217404
TI  - High-density EEG characterization of brain responses to auditory rhythmic stimuli
      during wakefulness and NREM sleep.
AB  - Auditory rhythmic sensory stimulation modulates brain oscillations by increasing
      phase-locking to the temporal structure of the stimuli and by increasing the
      power of specific frequency bands, resulting in Auditory Steady State Responses
      (ASSR). The ASSR is altered in different diseases of the central nervous system
      such as schizophrenia. However, in order to use the ASSR as biological markers
      for disease states, it needs to be understood how different vigilance states and
      underlying brain activity affect the ASSR. Here, we compared the effects of
      auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep,
      investigated the influence of the presence of dominant sleep rhythms on the ASSR,
      and delineated the topographical distribution of these modulations. Participants
      (14 healthy males, 20-33 years) completed on the same day a 60 min nap session
      and two 30 min wakefulness sessions (before and after the nap). During these
      sessions, amplitude modulated (AM) white noise auditory stimuli at different
      frequencies were applied. High-density EEG was continuously recorded and time
      frequency analyses were performed to assess ASSR during wakefulness and NREM
      periods. Our analysis revealed that depending on the electrode location,
      stimulation frequency applied and window/frequencies analysed the ASSR was
      significantly modulated by sleep pressure (before and after sleep), vigilance
      state (wake vs. NREM sleep), and the presence of slow wave activity and sleep
      spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep
      but not during wakefulness. Thus, (1) electrode location, sleep history,
      vigilance state and ongoing brain activity needs to be carefully considered when
      investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent
      a powerful tool to boost sleep spindles.

PMID- 29217407
TI  - Can we predict intermediate syndrome? A review.
AB  - INTRODUCTION: Ingestion of organophosphorus insecticides (OPI) is a common method
      of deliberate self harm in the developing world. Deaths mainly follow as a result
      of the respiratory failure associated with both cholinergic crisis and the
      intermediate syndrome. Even though death can be prevented by early mechanical
      ventilation of these patients, limited studies are available regarding the
      prediction of intermediate syndrome and subsequent respiratory failure.
      OBJECTIVE: To systematically review articles that are published with regard to
      possible prediction of intermediate syndrome using clinical, biochemical and
      electrophysiological parameters. METHODS: A systematic review on literature
      published in English language was done in the PubMed database without a date
      limitation. Two sets of search terms were used. The first set consisted of MeSH
      Terms "organophosphates", "organophosphate poisoning", "op poisoning"
      "organophosphate insecticide poisoning" and "organophosphorus". The second set
      included the MeSH Terms "Intermediate syndrome", "proximal muscle weakness",
      "cranial nerve palsies", "respiratory depression" and "neck muscle weakness".
      Articles containing at least one word from each set were reviewed. RESULTS: At
      least one MeSH term from each set was incorporated in 179 articles. Of these, 69
      were rejected as they were not related to organophosphate poisoning or
      intermediate syndrome. PREDICTION OF IMS: Clinical prediction is mostly based on
      ICU scoring systems. Biochemical markers such as reduced levels of serum and
      erythrocyte acetylcholine esterase have been studied many times. Both clinical
      and biochemical markers show a modest relationship in predicting IMS. Single
      fibre electromyography show promising results as it directly assesses
      neuromuscular junction. CONCLUSION: The intermediate syndrome which follows
      organophosphate poisoning still remains a significant problem with its high
      morbidity. Clinical and biochemical markers show modest results in predicting
      IMS. Neurophysiological markers such as single fibre EMG should be studied
      further as they measure activity of affected nicotinic receptors directly.

PMID- 29217408
TI  - Life, Surgery, and the Philosophy of Dry Creek.

PMID- 29217409
TI  - Proteasome phosphorylation regulates cocaine-induced sensitization.
AB  - Repeated exposure to cocaine produces structural and functional modifications at
      synapses from neurons in several brain regions including the nucleus accumbens.
      These changes are thought to underlie cocaine-induced sensitization. The
      ubiquitin proteasome system plays a crucial role in the remodeling of synapses
      and has recently been implicated in addiction-related behavior. The ATPase Rpt6
      subunit of the 26S proteasome is phosphorylated by Ca2+/calmodulin-dependent
      protein kinases II alpha at ser120 which is thought to regulate proteasome
      activity and distribution in neurons. Here, we demonstrate that Rpt6
      phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine
      concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in
      cultured neurons and in various brain regions of wild type mice including the
      nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase
      proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we
      found a complete absence of cocaine-induced locomotor sensitization in the Rpt6
      ser120Asp mice. Together, these findings suggest a critical role for Rpt6
      phosphorylation and proteasome function in the regulation cocaine-induced
      behavioral plasticity.

PMID- 29217410
TI  - Munc18-1 haploinsufficiency impairs learning and memory by reduced synaptic
      vesicular release in a model of Ohtahara syndrome.
AB  - Ohtahara syndrome, also known as type 4 of Early Infantile Epileptic
      Encephalopathy with suppression bursts (EIEE-4) is currently an untreatable
      disorder that presents with seizures and impaired cognition. EIEE-4 patients have
      mutations most frequently in the STXBP1 gene encoding a Sec protein, munc18-1.
      The exact molecular mechanism of how these munc18-1 mutations cause impaired
      cognition, remains elusive. The leading haploinsufficiency hypothesis posits that
      mutations in munc18-1 render the protein unstable leading to its degradation.
      Expression driven by the healthy allele is not sufficient to maintain the
      physiological function resulting in haploinsufficiency. The aim of this study has
      been to understand how munc18-1 haploinsufficiency causes cognitive impairment
      seen in EIEE-4. Here we present results from behavioral to cellular effects from
      a mouse model of munc18-1 haploinsufficiency. Munc18-1 heterozygous knock-out
      mice showed impaired spatial learning and memory in behavior tests as well as
      reduced synaptic plasticity in hippocampal CA1 long-term potentiation. Cultured
      munc18-1 heterozygous hippocampal neurons had significantly slower rate of
      synaptic vesicle release and decreased readily releasable vesicle pool compared
      to wild-type control neurons in fluorescent FM dye assays. These results
      demonstrate that reduced munc18-1 levels are sufficient to impair learning and
      memory by reducing neurotransmitter release. Therefore, our study implicates
      munc18-1 haploinsufficiency as a primary cause of cognitive impairment seen in
      EIEE-4 patients.

PMID- 29217411
TI  - CT after Endovascular Repair of Abdominal Aortic Aneurysms: Diagnostic Accuracy
      of Diameter Measurements for the Detection of Aneurysm Sac Enlargement.
AB  - PURPOSE: To evaluate the diagnostic accuracy of diameter measurements for the
      detection of aneurysm volume increase during follow-up after endovascular aortic
      repair (EVAR) of abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: This
      retrospective study analyzed 100 pairs of follow-up computed tomography scans
      randomly selected from an EVAR database (male/female ratio, 91/9; mean age, 71 y;
      bifurcated and aortouniiliac stent grafts, 96% and 4%, respectively; mean
      interval, 359 d). Five maximum diameter (Dmax) values were measured
      (anteroposterior, transverse, axial, coronal, and perpendicular). Aneurysm sac
      volume was measured by manual segmentation and used as the standard of reference.
      Overall, 37% of patients had a persistent type II endoleak. RESULTS: The
      anteroposterior, transverse, axial, coronal, and perpendicular Dmax values
      increased in 39 patients (mean, 4.3 mm), 30 patients (mean, 4.0), 35 patients
      (mean, 3.9 mm), 43 patients (mean, 3.9 mm), and 41 patients (mean, 4.3 mm),
      respectively. Aneurysm sac volume increased in 39 patients (mean, 25.7 cm3). The
      cutoff levels according to the reporting standard for aneurysm sac enlargement
      (diameter >= 5.0 mm, volume >= 5.0%) had sensitivity/specificity rates of
      29%/95%, 33%/97%, 29%/99%, 33%/93%, and 38%/96%, respectively, for the five Dmax
      values. The reference standards failed to detect aneurysm volume increase in 72%,
      67%, 72%, 61%, and 67% of patients, respectively, with persistent type II
      endoleak. CONCLUSIONS: Depending on the chosen cutoff value, diameter
      measurements showed low to moderate sensitivity for the detection of aneurysm
      volume increase. The diameter measurements failed to detect aneurysm enlargement
      in a large number of patients with persistent type II endoleak after EVAR of AAA.

PMID- 29217412
TI  - Glucagon-like peptide-1 receptor agonists reduced the low-density lipoprotein
      cholesterol in Japanese patients with type 2 diabetes mellitus treated with
      statins.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) often have
      hypercholesterolemia, and their serum low-density lipoprotein cholesterol (LDL-C)
      levels are not always well-controlled even by statin treatment. The glucose
      lowering glucagon-like peptide-1 receptor agonists (GLP-1RAs) are reported to
      change the lipid profiles in T2DM patients, but their effects have been unclear.
      OBJECTIVE: We examined whether GLP-1RAs affect serum cholesterol levels in T2DM
      patients with/without statin treatment. METHODS: We retrospectively assessed the
      baseline and follow-up (median 119 days) levels of serum lipids, HbA1c, and body
      mass index (BMI) in 103 and 214 Japanese patients with T2DM in whom GLP-1RAs were
      initiated (GLP-1RA group) and not initiated (control group), stratified by the
      use of statins. RESULTS: In the GLP-1RA group, the LDL-C, HbA1c, and BMI
      significantly decreased; high-density lipoprotein cholesterol and triglycerides
      did not decrease during follow-up. In the control group, these did not decrease.
      Among the statin users, the percentage change in LDL-C during follow-up was
      significantly greater in the GLP-1RA group than that in the control group (-6.5%
      vs -1.0%, P = .040). In the GLP-1RA group, the percentage reduction in LDL-C was
      not associated with that in BMI but was associated with that in HbA1c only among
      the statin users. CONCLUSIONS: Our findings demonstrated that GLP-1RAs reduced
      the serum LDL-C in Japanese patients with T2DM treated with statins. The
      percentage reduction in LDL-C by GLP-1RAs was associated with that in HbA1c, but
      not associated with that in BMI. The combination of GLP-1RAs and statins may be a
      reasonable therapeutic option in T2DM with dyslipidemia.

PMID- 29217413
TI  - Apolipoprotein E-containing high-density lipoprotein (HDL) modifies the impact of
      cholesterol-overloaded HDL on incident coronary heart disease risk: A community
      based cohort study.
AB  - BACKGROUND: Experimental studies have shown that cholesterol-overloaded high
      density lipoprotein (HDL) can promote the formation of apolipoprotein E (APOE)
      containing HDL, a process correcting the atherogenic function of cholesterol
      overloaded HDL. OBJECTIVE: The objective of the study was to explore whether APOE
      containing HDL can attenuate the defective impact of cholesterol-overloaded HDL
      on the development of coronary heart disease (CHD) in humans. METHODS: We
      measured APOE-HDL cholesterol (APOE-HDLC), HDL cholesterol (HDLC), and HDL
      particle number in 1112 participants aged 45 to 74 years at baseline in a
      community-based cohort study. Cholesterol molecules per HDL particle (HDL-C/P
      ratio) were calculated as the ratio of HDLC to HDL particle number. The ratio of
      APOE-HDLC to total HDLC (APOE-HDLC/HDLC ratio) was calculated to assess the
      relative proportion of APOE-HDLC in total HDLC. RESULTS: The HDL-C/P ratio was
      strongly correlated with APOE-HDLC (partial-r: 0.615). Participants with
      cholesterol-overloaded HDL (indicated by the highest level of the HDL-C/P ratio)
      had a high APOE-HDLC/HDLC ratio. Baseline cholesterol-overloaded HDL
      significantly increased the 10-year risk of incident CHD (hazard ratio = 2.42;
      95% confidence interval = 1.06-8.32), but this was attenuated by an increased
      APOE-HDLC/HDLC ratio. Participants with high HDL-C/P ratio and APOE-HDLC/HDLC
      ratio had a 42% lower risk, whereas those with a high HDL-C/P ratio and low APOE
      HDLC/HDLC ratio had a 2.54-fold higher risk, than those with low HDL-C/P ratio
      and APOE-HDLC/HDLC ratio after multiple adjustments. CONCLUSION: Cholesterol
      overloaded HDLs are related with increased APOE-containing HDL species. APOE
      containing HDL was found to attenuate the impact of cholesterol-overloaded HDL on
      increased incident CHD risk, suggesting that APOE-containing HDL may correct the
      dysfunction of cholesterol-overloaded HDL.

PMID- 29217414
TI  - Yellow Fever Vaccine for People Living With HIV Infection.

PMID- 29217416
TI  - Identification of target proteins of clinical immunity to Plasmodium falciparum
      in a region of low malaria transmission.
AB  - The target molecules of antibodies against falciparum malaria remain largely
      unknown. Recently we have identified multiple proteins as targets of immunity
      against Plasmodium falciparum using African serum samples. To investigate whether
      potential targets of clinical immunity differ with transmission intensity, we
      assessed immune responses in residents of low malaria transmission region in
      Thailand. Malaria asymptomatic volunteers (Asy: n=19) and symptomatic patients
      (Sym: n=21) were enrolled into the study. Serum immunoreactivity to 186 wheat
      germ cell-free system (WGCFS)-synthesized recombinant P. falciparum asexual-blood
      stage proteins were determined by AlphaScreen, and subsequently compared between
      the study groups. Forty proteins were determined as immunoreactive with antibody
      responses to 35 proteins being higher in Asy group than in Sym group. Among the
      35 proteins, antibodies to MSP3, MSPDBL1, RH2b, and MSP7 were significantly
      higher in Asy than Sym (unadjusted p<0.005) suggesting these antigens may have a
      protective role in clinical malaria. MSP3 reactivity remained significantly
      different between Asy and Sym groups even after multiple comparison adjustments
      (adjusted p=0.033). Interestingly, while our two preceding studies using African
      sera were conducted differently (e.g., cross-sectional vs. longitudinal design,
      observed clinical manifestation vs. functional activity), those studies similarly
      identified MSP3 and MSPDBL1 as potential targets of protective immunity. This
      study further provides a strong rationale for the application of WGCFS-based
      immunoprofiling to malaria vaccine candidate and biomarker discovery even in low
      or reduced malaria transmission settings.

PMID- 29217415
TI  - Arima syndrome caused by CEP290 specific variant and accompanied with
      pathological cilium; clinical comparison with Joubert syndrome and its related
      diseases.
AB  - OBJECTIVE: Arima syndrome (AS) is a rare disease and its clinical features mimic
      those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently,
      we clarified the AS diagnostic criteria and its severe phenotype. However,
      genetic evidence of AS remains unknown. We explored causative genes of AS and
      compared the clinical and genetic features of AS with the other JSRD. PATIENTS
      AND METHODS: We performed genetic analyses of 4 AS patients of 3 families with
      combination of whole-exome sequencing and Sanger sequencing. Furthermore, we
      studied cell biology with the cultured fibroblasts of 3 AS patients. RESULTS: All
      patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or
      compound heterozygous variants (c.1711+1G>A; c.6012-12T>A,
      p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene.
      These unique variants lead to abnormal splicing and premature termination.
      Morphological analysis of cultured fibroblasts from AS patients revealed a marked
      decrease of the CEP290-positive cell number with significantly longer cilium and
      naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm.
      CONCLUSION: AS resulted in cilia dysfunction from centrosome disruption. The
      unique variant of CEP290 could be strongly linked to AS pathology. Here, we
      provided AS specific genetic evidence, which steers the structure and functions
      of centrosome that is responsible for normal ciliogenesis. This is the first
      report that has demonstrated the molecular basis of Arima syndrome.

PMID- 29217417
TI  - Cat fleas (Ctenocephalides felis) carrying Rickettsia felis and Bartonella
      species in Hong Kong.
AB  - Fleas are commonly recorded on stray as well as domestic dogs and cats in Hong
      Kong. Fleas can be a major cause of pruritus in dogs and cats and also vectors of
      potentially zoonotic bacteria in the genera Rickettsia and Bartonella.
      Morphological examination of 174 fleas from dogs and cats living in Hong Kong
      revealed only cat fleas (Ctenocephalides felis). Cytochrome c oxidase subunit 1
      gene (cox1) genotyping of 20 randomly selected specimens, revealed three cox1
      haplotypes (HK-h1 to HK-h3). The most common haplotype was HK-h1 with 17
      specimens (17/20, 85%). HK-h1 was identical to cox1 sequences of fleas in
      Thailand and Fiji. HK-h1 and HK-h2 form a distinct cat flea cox1 clade previously
      recognized as the Clade 3. HK-h3 forms a new Clade 6. A multiplex Bartonella and
      Rickettsia real-time PCR of DNA from 20 C. felis found Bartonella and Rickettsia
      DNA in three (15%) and ten (50%) C. felis, respectively. DNA sequencing confirmed
      the presence of R. felis, B. clarridgeiae and Bartonella henselae. This is the
      first reported study of that kind in Hong Kong, and further work is required to
      expand the survey of companion animals in the geographical region. The sampling
      of fleas on domestic cats and dogs in Hong Kong revealed them to be exclusively
      infested by the cat flea and to be harbouring pathogens of zoonotic potential.

PMID- 29217418
TI  - Molecular characterization of virulence and antimicrobial resistance profile of
      Shigella species isolated from children with moderate to severe diarrhea in
      northeastern Brazil.
AB  - Molecular characterization of virulence and antimicrobial resistance profiles
      were determined for Shigella species isolated from children with diarrhea in
      Fortaleza, Brazil. Fecal specimens were collected along with socioeconomic and
      clinical data from children with moderate to severe diarrhea requiring emergency
      care. Shigella spp. were isolated by standard microbiological techniques, and we
      developed 4 multiplex polymerase chain reaction assays to detect 16 virulence
      related genes (VRGs). Antimicrobial susceptibility tests were performed using
      disk diffusion assays. S. flexneri and S. sonnei were the predominant serogroups.
      S. flexneri was associated with low monthly incomes; more severe disease; higher
      number of VRGs; and presence of pic, set, and sepA genes. The SepA gene was
      associated with more intense abdominal pain. S. flexneri was correlated with
      resistance to ampicillin and chloramphenicol, whereas S. sonnei was associated
      with resistance to azithromycin. Strains harboring higher numbers of VRGs were
      associated with resistance to more antimicrobials. We highlight the correlation
      between presence of S. flexneri and sepA, and increased virulence and suggest a
      link to socioeconomic change in northeastern Brazil. Additionally, antimicrobial
      resistance was associated with serogroup specificity in Shigella spp. and
      increased bacterial VRGs.

PMID- 29217419
TI  - In vitro activity of tedizolid against the Mycobacterium abscessus complex.
AB  - Infections due to Mycobacterium abscessus carry a poor prognosis since this
      rapidly growing mycobacterium is intrinsically resistant to most antibiotics.
      Here, we evaluate the in vitro activity of the new oxazolidinone tedizolid
      against a collection of 44M. abscessus clinical isolates. The MIC50s and MIC90s
      of tedizolid (2 and 8MUg/mL, respectively) were 2- to 16-fold lower than those of
      linezolid. There was no difference between the 3M. abscessus subspecies. Time
      kill assays did not show any bactericidal activity at 4- and 8-fold the MIC.
      Combination of tedizolid with clarithromycin was synergistic against 1 out of 6
      isolates, while indifferent interactions were observed for tedizolid combined
      with tigecycline, ciprofloxacin, and amikacin.

PMID- 29217420
TI  - Antibody test for Legionella pneumophila detection.
AB  - Legionella pneumophila is responsible for Legionnaires' disease (LD). Its
      detection in both environmental and clinical samples is mainly performed by
      culture plate method which requires up to 10days to obtain results. Nowadays,
      there are commercial antibodies against this bacterium, but they have not been
      tested against all subgroups of L. pneumophila sg 1 or serogroups 1-16 or their
      cross-reactions with other non-Legionella bacteria. Indeed, many of these
      antibodies became available when only 8 serogroups of L. pneumophila had been
      described. We tested 7 antibodies and found that 2 (Mab 8/5 and OBT) specifically
      detected all the subgroups of L. pneumophila sg 1, one without cross-reactions
      (Mab8/5). Moreover, the LP3IIG2 antibody detected almost all serogroups tested
      with lower rates of cross-reactivity, resulting in a specific sensitive antibody
      for the detection of L. pneumophila. LP3IIG2 presented higher rate of cross
      reactivity against respiratory non-Legionella isolates, thereby contraindicating
      its clinical applicability.

PMID- 29217421
TI  - Isolated suprascapular mononeuropathy following nondisplaced scapular fracture.

PMID- 29217422
TI  - Hyperbaric oxygen ameliorated the lesion scope and nerve function in acute spinal
      cord injury patients: A retrospective study.
AB  - OBJECTIVE: This is a retrospective study to assess the therapeutic effect of
      hyperbaric oxygen (HBO) in early treatment of acute spinal cord injury (SCI)
      using magnetic resonance imaging (MRI) and electrophysiology in diagnosing.
      METHODS: Forty acute SCI patients from Sun Yat-Sen Memorial Hospital who were
      assigned into HBO treatment were included during August 2013 to October 2014.The
      patients with adverse reactions or contraindications for HBO were assigned as
      controls. Both of two groups (HBO and Control) received medicine treatment with
      Urbason, GM-1 and mecobalamine after surgery. ASIA and the Frankel scores were
      used to evaluate the therapeutic effect of HBO at the 15th and 30th day after HBO
      treatment by using MRI and electrophysiology features. RESULTS: Significant
      therapeutic effect of HBO treatment on acute SCI patients was observed compared
      with the control group (P<0.05). Comparison for ASIA and Frankel scores showed
      that motor and neurological functions were significantly improved in HBO group at
      day 15 and day 30 post treatment. MRI images showed that the grade III injury in
      HBO group was significant lower than the control group. In comparison with the
      control, the peak of somatosensory evoked potential (SEP) and motor evoked
      potential (MEP) amplitude increased, the latency was shortened, and the
      conduction velocity of sensory nerve (SCV) and motor nerve (MCV) was
      significantly increased in the HBO group (P<0.05). CONCLUSIONS: HBO treatment has
      a great efficacy in acute SCI patients. HBO therapy at early stage of acute SCI
      is beneficiary to the recovery.

PMID- 29217423
TI  - Pre-transplant AT1R antibodies correlate with early allograft rejection.
AB  - Studies investigating the potential pathogenic effects of non-HLA antibodies (Ab)
      have identified Ab against the angiotensin II type 1 receptor (AT1R-Ab) as a risk
      factor for rejection and kidney graft loss. This study sought to validate the
      risk of AT1R-Ab for acute rejection and to explore the role of other non-HLA Abs
      in this capacity. Pre- and post-transplant sera from a cohort of 101 patients
      (n=453 samples total) were tested for AT1R-Ab and other non-HLA Ab using a
      commercially available ELISA kit and the Luminex platform, respectively. Patients
      positive for pre-transplant AT1R-Ab were more likely to develop de novo donor
      specific Ab (dnDSA) compared to patients that were negative for AT1R-Ab (28% vs
      10%, p=0.027). Pre-transplant positivity for AT1R-Ab was associated with TCMR in
      the first year post-transplant (p=0.034), but did not predict graft loss
      independent of dnDSA (p=0.063). AT1R-Ab positivity was significantly associated
      with positivity for Ab against the endothelin A type 1 receptor (ETAR-Ab)
      inclusive of all study time points (p=0.0021). Given the high prevalence of AT1R
      Ab pre-transplant (20%) and its association with dnDSA and early TCMR, a
      prospective study to determine if more intense immunosuppression and/or AT1R
      blockade has an impact on outcomes in these patients is warranted.

PMID- 29217424
TI  - Modelling the impact of future socio-economic and climate change scenarios on
      river microbial water quality.
AB  - Microbial surface water quality is important, as it is related to health risk
      when the population is exposed through drinking, recreation or consumption of
      irrigated vegetables. The microbial surface water quality is expected to change
      with socio-economic development and climate change. This study explores the
      combined impacts of future socio-economic and climate change scenarios on
      microbial water quality using a coupled hydrodynamic and water quality model
      (MIKE21FM-ECOLab). The model was applied to simulate the baseline (2014-2015) and
      future (2040s and 2090s) faecal indicator bacteria (FIB: E. coli and enterococci)
      concentrations in the Betna river in Bangladesh. The scenarios comprise changes
      in socio-economic variables (e.g. population, urbanization, land use, sanitation
      and sewage treatment) and climate variables (temperature, precipitation and sea
      level rise). Scenarios have been developed building on the most recent Shared
      Socio-economic Pathways: SSP1 and SSP3 and Representative Concentration Pathways:
      RCP4.5 and RCP8.5 in a matrix. An uncontrolled future results in a deterioration
      of the microbial water quality (+75% by the 2090s) due to socio-economic changes,
      such as higher population growth, and changes in rainfall patterns. However,
      microbial water quality improves under a sustainable scenario with improved
      sewage treatment (-98% by the 2090s). Contaminant loads were more influenced by
      changes in socio-economic factors than by climatic change. To our knowledge, this
      is the first study that combines climate change and socio-economic development
      scenarios to simulate the future microbial water quality of a river. This
      approach can also be used to assess future consequences for health risks.

PMID- 29217425
TI  - USP6 gene rearrangement differentiates primary paranasal sinus solid aneurysmal
      bone cyst from other giant cell-rich lesions: report of a rare case.
AB  - Aneurysmal bone cysts (ABCs) mostly occur in the metaphysis of long bones.
      Primary paranasal ABCs are extremely rare, and most reported cases reveal typical
      histopathological features including cystic space with fibrous septa and
      hemorrhage. Solid-variant ABCs or solid ABCs lacking cyst formation may be
      histologically indistinguishable from giant cell reparative granulomas, giant
      cell tumor of bone, and brown tumor. Here we report the case of a 24-year-old
      woman with a paranasal mass diagnosed as USP6-rearranged solid ABC, mimicking
      giant cell reparative granuloma, giant cell tumor of bone, and brown tumor. For
      paranasal sinus bone or soft tissue tumors containing numerous giant cells,
      molecular analysis including the USP6 gene may serve as a useful diagnostic tool
      to distinguish solid ABCs from other giant cell-rich lesions.

PMID- 29217426
TI  - Composite lymphoma of follicular B-cell and peripheral T-cell types with distinct
      zone distribution in a 75-year-old male patient: a case study.
AB  - Composite lymphoma of T-/B-cell type is rare, and follicular lymphoma composite
      with peripheral T-cell lymphoma (PTCL) has not previously been reported. We
      report such a case with both neoplastic components displaying a unique zone of
      distribution. A 75-year-old male patient presented with generalized
      lymphadenopathy. Sections of axillary lymph node demonstrated potentially 2
      clonal processes, PTCL with aberrant CD20 expression and follicular lymphoma.
      Interestingly, the 2 neoplastic components were confined to their respective
      classic distribution zones, with PTCL occupying the interfollicular areas and
      follicular lymphoma residing in follicles. Both populations were detected by flow
      cytometry, but their immunophenotypes were insufficient to define clonality.
      Nonetheless, biclonality was demonstrated by lymphoid receptor gene rearrangement
      analyses. Molecular cytogenetics showed IGH/BCL2 fusion in the follicular
      lymphoma and amplification of IGH gene or trisomy/tetrasomy 14 in the PTCL. The
      current case underscores the complexity of composite lymphoma and advocates a
      multimodal approach to establishing the diagnosis.

PMID- 29217427
TI  - Incidental iatrogenic form of collagenized organizing pneumonia.

PMID- 29217428
TI  - Clinical significance of GalNAcylated glycans in cholangiocarcinoma: Values for
      diagnosis and prognosis.
AB  - Cancer cells exhibited the aberrant cancer-associated glycans that are potential
      biomarkers for diagnosis and monitoring of the cancer. In this study, Sophora
      japonica agglutinin (SJA) was used to detect SJA-specific N-acetylgalactosamine
      associated glycans (SNAG) in liver tissues and sera from cholangiocarcinoma (CCA)
      patients. Whether SNAG could be the diagnostic and prognostic markers for CCA was
      evaluated. SJA-histochemistry revealed that SNAG was undetec2 in normal bile
      ducts but was highly expressed in hyperplastic/dysplastic bile ducts and CCA.
      SNAG was negative in hepatocytes and hepatoma tissues indicating SNAG as a
      differential marker of CCA and hepatoma. SJA-histochemistry of CCA hamster
      tissues revealed the involvement of SNAG in the early pathogenesis of bile duct
      epithelia and CCA development. A SJA-based ELISA was successfully developed to
      determine SNAG in serum. Serum-SNAG from CCA patients was significantly higher
      than those of non-CCA control groups with the diagnostic values of 59.5%
      sensitivity and 73.6% specificity, comparable to those of serum CA19-9. High
      levels of serum SNAG (>=69AU/ml) indicated poor survival of CCA patients. Taken
      together, SNAG was first demonstrated here to be a glycobiomarker for diagnosis
      and prognosis of CCA. Association of SNAG with pathogenesis of bile ducts and CCA
      development were suggested. (198).

PMID- 29217429
TI  - Association of platelet count with sarcopenic obesity in postmenopausal women: A
      nationwide population-based study.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between
      platelet count and sarcopenic obesity in postmenopausal women. METHOD: This cross
      sectional study was conducted using nationally representative data. A total of
      2810 postmenopausal women who participated in the 2008-2011 Korea National Health
      and Nutrition Examination Survey were included in this study. Sarcopenic obesity
      was defined by a sarcopenia criterion and an obesity criterion. Platelet counts
      were divided into quartiles as follows: Q, 150-222; Q2, 223-257; Q3, 258-294, and
      Q4, 295-450 (103/MUl). Multiple logistic regression analysis was performed to
      examine the association between platelet count quartile and sarcopenic obesity
      after adjusting for confounding factors. RESULTS: The prevalence of sarcopenic
      obesity in postmenopausal women was 14.8%. Compared to the lowest platelet
      quartile, the odds ratios and 95% confidence intervals for sarcopenic obesity in
      the highest quartile were 1.98 (1.36-2.89) in the unadjusted model; 1.93 (1.31
      2.83) after adjusting for age; and 1.65 (1.23-2.65) after adjusting for age,
      systolic blood pressure, homeostatic model assessment insulin resistance (HOMA
      IR), triglyceride, total cholesterol, total calorie intake, regular exercise,
      current smoking status, and education level. CONCLUSIONS: Elevated platelet count
      (i.e. towards the upper end of the normal range) was significantly associated
      with sarcopenic obesity in postmenopausal women.

PMID- 29217430
TI  - Letter re: Diagnosis of ventriculostomy-related infection: Is cerebrospinal fluid
      lactate measurement a useful tool?

PMID- 29217431
TI  - The effects of load on transmural differences in contraction of isolated mouse
      ventricular cardiomyocytes.
AB  - Mechanical properties of cardiomyocytes from different transmural regions are
      heterogeneous in the left ventricular wall. The cardiomyocyte mechanical
      environment affects this heterogeneity because of mechano-electric feedback
      mechanisms. In the present study, we investigated the effects of the mechanical
      load (preload and afterload) on transmural differences in contraction of
      subendocardial (ENDO) and subepicardial (EPI) single cells isolated from the
      murine left ventricle. Various preloads imposed via axial stretch and afterloads
      (unloaded and heavy loaded conditions) were applied to the cells using carbon
      fiber techniques for single myocytes. To simulate experimentally obtained results
      and to predict mechanisms underlying the cellular response to change in load, our
      mathematical models of the ENDO and EPI cells were used. Our major findings are
      the following. Our results show that ENDO and EPI cardiomyocytes have different
      mechanical responses to changes in preload to the cells. Under auxotonic
      contractions at low preload (unstretched cells), time to peak contraction (Tmax)
      and the time constant of [Ca2+]i transient decay were significantly longer in
      ENDO cells than in EPI cells. An increase in preload (stretched cells) prolonged
      Tmax in both cell types; however, the prolongation was greater in EPI cells,
      resulting in a decrease in the transmural gradient in Tmax at high preload.
      Comparing unloaded and heavy loaded (isometric) contractions of the cells we
      found that transmural gradient in the time course of contraction is independent
      of the loading conditions. Our mathematical cell models were able to reproduce
      the experimental results on the distinct cellular responses to changes in the
      mechanical load when we accounted for an ENDO/EPI difference in the parameters of
      cooperativity of calcium activation of myofilaments.

PMID- 29217432
TI  - Transverse tubular network structures in the genesis of intracellular calcium
      alternans and triggered activity in cardiac cells.
AB  - RATIONALE: The major role of a transverse-tubular (TT) network in a cardiac cell
      is to facilitate effective excitation-contraction coupling and signaling. The TT
      network structures are heterogeneous within a single cell, and vary between
      different types of cells and species. They are also remodeled in cardiac
      diseases. However, how different TT network structures predispose cardiac cells
      to arrhythmogenesis remains to be revealed. OBJECTIVE: To systematically
      investigate the roles of TT network structure and the underlying mechanisms in
      the genesis of intracellular calcium (Ca2+) alternans and triggered activity
      (TA). METHODS AND RESULTS: Based on recent experimental observations, different
      TT network structures, including uniformly and non-uniformly random TT
      distributions, were modeled in a cardiac cell model consisting of a three
      dimensional network of Ca2+ release units (CRUs). Our simulations showed that
      both Ca2+ alternans and Ca2+ wave-mediated TA were promoted when the fraction of
      orphaned CRUs was in an intermediate range, but suppressed in cells exhibiting
      either well-organized TT networks or low TT densities. Ca2+ alternans and TA
      could be promoted by low TT densities when the cells were small or the CRU
      coupling was strong. Both alternans and TA occurred more easily in uniformly
      random TT networks than in non-uniformly random TT networks. Subcellular
      spatially discordant Ca2+ alternans was promoted by non-uniformly random TT
      networks but suppressed by increasing CRU coupling strength. These mechanistic
      insights provide a holistic understanding of the effects of TT network structure
      on the susceptibility to arrhythmogenesis. CONCLUSIONS: The TT network plays
      important roles in promoting Ca2+ alternans and TA, and different TT network
      structures may predispose cardiac cells differently to arrhythmogenesis.

PMID- 29217433
TI  - Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar
      disarray and pro-arrhythmic action potential changes in human iPSC
      cardiomyocytes.
AB  - BACKGROUND: Mutations in cardiac troponin T (TnT) are linked to increased risk of
      ventricular arrhythmia and sudden death despite causing little to no cardiac
      hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)
      associated TnT-I79N mutation increases myofilament Ca sensitivity and is
      arrhythmogenic, but whether findings from mice translate to human cardiomyocyte
      electrophysiology is not known. OBJECTIVES: To study the effects of the TnT-I79N
      mutation in human cardiomyocytes. METHODS: Using CRISPR/Cas9, the TnT-I79N
      mutation was introduced into human induced pluripotent stem cells (hiPSCs). We
      then used the matrigel mattress method to generate single rod-shaped
      cardiomyocytes (CMs) and studied contractility, Ca handling and
      electrophysiology. RESULTS: Compared to isogenic control hiPSC-CMs, TnT-I79N
      hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and
      impaired relaxation. The Ca-dependence of contractility was leftward shifted in
      mutation containing cardiomyocytes, demonstrating increased myofilament Ca
      sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca
      transients by enhancing cytosolic Ca buffering. These changes in Ca handling
      resulted in beat-to-beat instability and triangulation of the cardiac action
      potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer
      EMD57033 produced similar action potential triangulation in control hiPSC-CMs.
      CONCLUSIONS: The TnT-I79N hiPSC-CM model not only reproduces key cellular
      features of TnT-linked HCM such as myofilament disarray, hypercontractility and
      diastolic dysfunction, but also suggests that this TnT mutation causes pro
      arrhythmic changes of the human ventricular action potential.

PMID- 29217434
TI  - Upper Limb Ischemia by Subclavian Artery Dissection after Osteopathic
      Manipulation.
AB  - We report the case of a young woman who experienced ischemia of upper limb after
      osteopathic manipulation. Duplex and computed tomography scan showed wall
      hematoma of the ostium of subclavian artery. The patient spontaneously recovered
      so that no surgery was necessary. Dissection of vertebral and carotid arteries
      has been reported after osteopathic manipulations. We report ischemia of upper
      limb secondary to dissection of subclavian artery. Arterial dissections
      associated with manipulation should be recorded in a register in order to assess
      more carefully the vascular risk that this method carries.

PMID- 29217435
TI  - Determination of Risk Factors and Establishment of a Prediction Model for
      Immediate Technical Failure during Endovascular Treatment of Femoropopliteal
      Occlusive Disease.
AB  - BACKGROUND: For long femoropopliteal occlusive lesions, the immediate technical
      failure (ITF) of endovascular treatment (EVT) is relatively high. Therefore, this
      study aims to reveal risk factors and establish a prediction model of ITF of EVT
      in femoropopliteal occlusive disease (FPOD) patients based on preoperative
      clinical date that may be helpful to the clinical procedures. METHODS: A
      retrospective analysis of 1,563 FPOD patients who underwent above-the-knee EVT
      was undertaken. Univariate analysis with chi-squared test was used to screen risk
      factors from preoperative clinical data. Multivariable analysis with logistic
      regression was used to generate a model for predicting the ITF rate of EVT, which
      was evaluated through the receiver operating characteristic curve and another
      independent cohort of 242 FPOD patients. RESULTS: Risk factors for ITF during EVT
      in FPOD included age (>80 years, X1), the absence of diabetes mellitus (X2), low
      density lipoprotein (>160 mg/dL, X3), lesion calcification (X4), lesion length
      (>20 cm, X5), ostial occlusion of superficial femoral artery (SFA) (X6), and SFA
      lesion involving the popliteal artery (X7). A logistic regression model was
      established based on the equation: -6.504 + 1.236X1 + 0.945X2 + 1.406X3 + 1.136X4
      + 1.059X5 + 2.307X6 + 2.194X7. Scores were given to risk factors as follows: X1
      (yes = 12, no = 0), X2 (yes = 9, no = 0), X3 (yes = 14, no = 0), X4 (yes = 11, no
      = 0), X5 (yes = 11, no = 0), X6 (yes = 23, no = 0), and X7 (yes = 22, no = 0). We
      determined that the optimal comprehensive score for predicting EVT failure was
      39, with a sensitivity of 0.847 and a specificity of 0.8. Among these 242
      peripheral arterial disease patients, 12 of 14 patients who had failed EVT had a
      comprehensive score of >39. CONCLUSIONS: We identified a number of risk factors
      of ITF during the above-the-knee EVT and established a prediction model that may
      be used for guidance in clinical practice.

PMID- 29217436
TI  - Endolymphatic Thoracic Duct Stent-Graft Reconstruction for Chylothorax: Approach,
      Technical Success, Safety, and Short-term Outcomes.
AB  - BACKGROUND: To report approach, technical success, safety, and short-term
      outcomes of thoracic duct stent-graft reconstruction for the treatment of
      chylothorax. METHODS: Two patients, 1 (50%) male and 1 (50%) female, with mean
      age of 38 years (range: 16-59 years) underwent endolymphatic thoracic duct stent
      graft reconstruction between September 2016 and July 2017. Patients had
      radiographic left-sided chylothoraces (n = 2) from idiopathic causes (n = 1) and
      heart transplantation (n = 1). In both (100%) patients, antegrade lymphatic
      access was used to opacify the thoracic duct after which retrograde access was
      used for thoracic duct stent-graft placement. Pelvic lymphangiography technical
      success, antegrade cisterna chyli cannulation technical success, thoracic duct
      opacification technical success, retrograde thoracic duct access technical
      success, thoracic duct stent-graft reconstruction technical success, ethiodized
      oil volume, contrast volume, estimated blood loss, procedure time, fluoroscopy
      time, radiation dose, clinical success, complications, deaths, and follow-up were
      recorded. RESULTS: Pelvic lymphangiography, antegrade cisterna chyli cannulation,
      thoracic duct opacification, retrograde thoracic duct access, and thoracic duct
      stent-graft reconstruction were technically successful in both (100%) patients.
      Mean ethiodized oil volume was 8 mL (range: 5-10 mL). Mean contrast volume was 13
      mL (range: 5-20 mL). Mean estimated blood loss was 13 mL (range: 10-15 mL). Mean
      fluoroscopy time was 50.4 min (range: 31.2-69.7 min). Mean dose area product and
      reference air kerma were 954.4 MUGmy2 (range: 701-1,208 MUGmy2) and 83.5 mGy
      (range: 59-108 mGy), respectively. Chylothorax resolved in both (100%) patients.
      There were no minor or major complications directly related to the procedure.
      CONCLUSIONS: Thoracic duct stent-graft reconstruction may be a technically
      successful and safe alternative to thoracic duct embolization, disruption, and
      surgical ligation for the treatment of chylothorax. Additional studies are
      warranted.

PMID- 29217437
TI  - Carotid Endarterectomy Performed before the Weekend is Associated with Increased
      Length of Stay.
AB  - OBJECTIVE: Length of stay (LOS) is commonly used to gauge hospital resource
      utilization and can affect hospital profit margin. Other fields of surgery have
      showed that operations performed close to the weekend have longer LOS and higher
      patient morbidity. Our goal was to investigate whether asymptomatic patients
      undergoing elective carotid endarterectomy (CEA) earlier in the week had a
      shorter LOS and improved clinical outcomes compared to those treated before the
      weekend. METHODS: The Vascular Quality Initiative database was queried for
      elective weekday CEAs performed for asymptomatic carotid stenosis from 2005 to
      2017. Univariate and multivariate analyses were completed to compare outcomes
      based on the day of the week. RESULTS: There were 26,882 asymptomatic CEAs
      performed on Monday (20.3%), Tuesday (23.0%), Wednesday (21.3%), Thursday
      (18.8%), and Friday (16.6%). The mean patient age was 70.5 years, and 59.2% were
      male. Thirty-day mortality (0.4%) and perioperative complications including
      stroke (1.4%), myocardial infarction (0.7%), and return to the operating room
      (1.5%) were not significantly different across weekdays. Patients were discharged
      on statins in 84.2% of cases and aspirin in 91.5% of cases. The mean LOS ranged
      from 1.6 +/- 2.2 days to 1.8 +/- 3.2 days. CEAs performed on Fridays had a longer
      LOS (1.8 +/- 2.4; P < 0.001). Multivariate analysis demonstrated that CEAs
      performed on Friday had longer LOS compared to those performed on Monday through
      Thursday (means ratio: 1.05, 95% confidence interval [CI]: 1.03-1.07; P < 0.001).
      However, there were no differences in perioperative complications to attribute
      this to. Friday CEA did not have an effect on discharge medication compliance
      with aspirin (odds ratio: 0.94, 95% CI: 0.82-1.07; P = 0.339) or statin
      medications (odds ratio: 0.90, 95% CI: 0.79-1.03; P = 0.126). CONCLUSION:
      Asymptomatic CEA performed before the weekend was associated with longer LOS
      although there were no differences in perioperative mortality, morbidity, and
      discharge medication compliance. Such LOS increase, albeit small, may affect the
      hospital profit margin for the procedure and performing an elective CEA on
      asymptomatic patients earlier in the week may benefit in a shorter LOS. Improved
      team staffing and resources on weekends are potential areas for improvement for
      earlier discharge; however, further investigation is needed.

PMID- 29217438
TI  - Bilateral Axillary Artery Aneurysms in a Six-Year-Old Child.
AB  - True axillary artery aneurysms in children are rare and mostly caused by blunt
      trauma. Idiopathic bilateral axillary aneurysms in children are even more
      infrequent, and evidence for optimal management is scarce. Moreover, the maximum
      follow-up time of interventions reported in pediatric axillary artery aneurysms
      was less than 1 year, and long-term outcomes remained unknown. In this report, we
      presented a 6-year-old child with bilateral axillary artery aneurysms treated by
      saphenous vein reconstruction with a 5-year follow-up. Meanwhile, we reviewed the
      etiology and treatment of true axillary artery aneurysm in children, which we
      hope would add information to the scarce evidence of management of true axillary
      artery aneurysms in children.

PMID- 29217439
TI  - In Patients with Severe Peripheral Arterial Disease, Revascularization-Induced
      Improvement in Lower Extremity Ischemia Can Be Detected by Laser Speckle Contrast
      Imaging of the Fluctuation in Blood Perfusion after Local Heating.
AB  - BACKGROUND: We previously reported the utility of the perfusion value (PV)
      fluctuation slope for detecting severe ischemia in the lower limb. Our approach
      was based on a thermal load test mimicking the well-known physiological reaction
      termed "cold-induced vasodilation," which is known to occur as a 3-phase
      phenomenon. The slope parameter quantifies the decrease in PVs accompanying the
      relative cooling (third phase) following the transient increase in blood flow
      (second phase) induced by the applied thermal load. This phenomenon of "relative"
      cold-induced vasodilation (rCIVD) can be monitored using laser speckle contrast
      imaging (LSCI) after applying the thermal load (LTL test). Here, we aimed to
      determine whether the slope parameter obtained via the LTL test also reflects the
      improvement in hemodynamics after revascularization. METHODS: The study enrolled
      16 patients (18 limbs), who underwent revascularization for peripheral arterial
      disease (PAD). The measurements were performed at 2 sites in each limb (in total,
      34 sites; 2 sites in one patient were excluded because of significant movement
      during the measurement). For each site, we recorded the slope describing the
      behavior of PVs (decrease or plateau) in the third phase of rCIVD, following the
      initial, heating-induced increase in perfusion (second phase of rCIVD). The
      plateau group (group P), which included patients with an abnormal rCIVD, and the
      decrease group (group D), which included patients with a normal rCIVD, were
      defined based on perfusion slope values of <0.20 and >= 0.20 perfusion units/min,
      respectively. We also quantified the transient increase in perfusion (from
      baseline to peak) as a descriptor of perfusion behavior during the second phase
      of rCIVD. RESULTS: In group P, the change in median values (25-75%) of the slope,
      transcutaneous oxygen tension, and ankle-brachial index (ABI) from before to
      after operation was (-0.02 [-0.04 to 0.02]; 4 [1-11]; and 0.08 [0-0.27]) to (0.39
      [0.32-0.59]; 46 [37-54]; and 0.81 [0.72-0.90]). Conversely, in group D, the
      change in the median values of the slope, transcutaneous oxygen tension, and ABI
      between before and after operation was (0.38 [0.32-0.49]; 40.5 [35-45]; and0.58
      [0.57-0.65]) to (0.44 [0.30-0.64]; 52 [43-56]; and 0.92 [0.81-0.99]). Sites
      exhibiting perfusion pattern of group D in the third phase of rCIVD showed no
      significant change in slope after revascularization (P = 0.21), whereas the slope
      in group P increased significantly after revascularization, becoming similar to
      the postoperative slopes in group D (P = 0.81). The amount of transient increase
      in perfusion, which quantified the behavior in the second phase of rCIVD, showed
      a similar behavior. Preoperatively, all patients in group P had rest pain and/or
      ulcer of the foot, whereas only few patients in group D had such symptoms.
      CONCLUSIONS: Normal rCIVD response in the LTL test indicates less-than-severe
      ischemia, while abnormal rCIVD response measured via the LTL test indicates
      severe ischemic symptoms, such as critical limb ischemia. Notably, patients with
      an abnormal rCIVD response can develop a normal rCIVD response following
      revascularization, thereby reflecting an improvement in blood flow. The LTL test
      assessing rCIVD response can be useful for detecting severe limb ischemia, such
      as critical limb ischemia (CLI), and determining the departure from severe limb
      ischemia by revascularization.

PMID- 29217440
TI  - Endolymphatic Balloon-Occluded Retrograde Abdominal Lymphangiography (BORAL) and
      Embolization (BORALE) for the Diagnosis and Treatment of Chylous Ascites:
      Approach, Technical Success, and Clinical Outcomes.
AB  - BACKGROUND: To describe endolymphatic balloon-occluded retrograde abdominal
      lymphangiography (BORAL) and embolization (BORALE) for diagnosis and treatment of
      chylous ascites in patients with previously unidentifiable leakage site or failed
      lymphatic embolization. METHODS: Two (66%) men and 1 (33%) woman with mean age of
      52 years (range: 14-79 years) presented with chylous ascites and underwent BORAL
      or BORALE between March 2016 and February 2017. Patients presented with chylous
      ascites (n = 3) and with renal cell carcinoma after left nephrectomy and lymph
      node dissection (n = 1), metastatic Merkel cell carcinoma after left nephrectomy
      and adrenalectomy (n = 1), and heart transplantation after failed Fontan
      procedure (n = 1). Pelvic lymphangiography technical successes, complications,
      radiation dose, contrast volume, clinical response, and follow-up were recorded.
      RESULTS: Pelvic lymphangiography and BORAL were technically successful in 3
      (100%) patients. BORALE was attempted in 2 (66%) patients and was technically
      successful in both patients (100%). No minor or major complications occurred.
      Mean radiation dose was 1,037 mGy (range: 391-2,264 mGy). Mean contrast was 83 mL
      (range: 25-150 mL). Mean blood loss was 15 mL (range: 5-30 mL). Chylous ascites
      resolved in all 3 (100%) patients. CONCLUSIONS: BORAL and BORALE provide a
      rational and effective approach for the diagnosis and treatment of patients with
      chylous ascites and previously unidentifiable leakage site or failed lymphatic
      embolization.

PMID- 29217441
TI  - Impact of Body Mass Index on Outcomes after Mesenteric Revascularization for
      Chronic Mesenteric Ischemia.
AB  - BACKGROUND: Historically, patients with chronic mesenteric ischemia (CMI) are
      underweight with a low body mass index (BMI). However, with the recent obesity
      epidemic many of these patients now are overweight with a high BMI. We evaluated
      the impact of BMI on outcomes after mesenteric revascularization for CMI.
      METHODS: A retrospective chart review of patients undergoing open or endovascular
      mesenteric revascularization for CMI between January 2000 and June 2015 was
      performed. Demographics, comorbidities, BMI, Society for Vascular Surgery
      combined comorbidity score, treatment modality, postoperative complications,
      reintervention, and all-cause mortality were analyzed. The primary end point for
      the study was all-cause mortality at 5 years. Patients were stratified using the
      World Health Organization BMI criteria. Univariate, Kaplan-Meier survival, and
      multivariate analyses were performed. RESULTS: In the study period, 104 unique
      patients underwent mesenteric revascularization for CMI, for 77 of whom BMI
      information was available. Of these 77, 30 patients were treated by endovascular
      revascularization, and 47 patients were treated by open revascularization.
      Overall, 27 (35.1%) were overweight or obese with a BMI >=25. Median follow-up
      time was 41 months. High BMI patients were less likely to have weight loss at the
      time of surgery (P = 0.004). Stratified by BMI <25 versus BMI >=25, 5-year
      survival for patients treated by open revascularization was 90% versus 50% (P =
      0.02); survival for patients treated by endovascular revascularization was 27%
      vs. 53% (P = 0.37). Multivariate survival analysis identified active smoking,
      hypertensive chronic kidney disease, open repair with the use of venous conduit
      instead of prosthetic conduit (P < 0.001), and history of peripheral arterial
      disease (PAD) (P = 0.002), as independent predictors of increased all-cause
      mortality. CONCLUSIONS: BMI needs to be considered in assessing and counseling
      patients on outcomes of mesenteric revascularization for CMI, as a BMI over 25 is
      associated with poorer long-term survival after open revascularization. Smoking,
      hypertensive chronic kidney disease, PAD, and open repair with the use of venous
      conduit are independent predictors of long-term mortality after mesenteric
      revascularization independent of BMI.

PMID- 29217442
TI  - Posterior Approach for Revascularization in Blunt Popliteal Vessel Injury.
AB  - BACKGROUND: Popliteal vessel injuries are associated with traumatic knee injury
      often requiring emergency revascularization. Medial and posterior approaches to
      the popliteal space have been proposed. This study evaluates the outcome of
      patients treated for traumatic popliteal vessel injuries via a posterior
      approach. METHODS: Consecutive patients with traumatic vascular injuries in the
      popliteal segments II and III undergoing surgical repair via a posterior approach
      between October 2008 and December 2016 were analyzed. The level of the arterial
      injury was preoperatively confirmed by computed tomography angiography or duplex
      ultrasound. Surgery was performed in prone position. Perioperative and long-term
      outcomes were analyzed including a survey of all patients in January 2017
      assessing survival, limb salvage, and claudication. RESULTS: Ten patients (8
      female; median age 66 years, range 22-88) with blunt knee trauma were identified,
      8 of them after spontaneous knee dislocation. Five patients had local intimal
      disruption and 5 had complete transection of the popliteal artery. In 6 patients,
      an interposition graft (vein n = 5; xenograft n = 1) was used for
      revascularization. Two patients underwent direct reanastomosis and in 2 patients
      longitudinal arteriotomy with patch plasty was performed. All arterial
      reconstructions were patent at discharge. Two patients had additional transection
      of the popliteal vein; in one, reconstruction was performed by direct
      reanastomosis and in another by interposition of a vein graft. The latter had
      asymptomatic early postoperative occlusion of the vein graft. After a median
      follow-up of 56 months (range 45-99), no death, limb loss, or claudication was
      observed. CONCLUSIONS: After traumatic knee injury, posterior approach to the
      popliteal vessels is feasible and effective. It allows revascularization by
      direct repair or a short segment interposition graft avoiding long distance
      bypass. A high limb salvage rate can be achieved with excellent long-term
      outcomes.

PMID- 29217443
TI  - Analysis of Aortic Growth Rates in Uncomplicated Type B Dissection.
AB  - BACKGROUND: Uncomplicated type B dissections have historically been treated
      medically with hemodynamic control. Early progression of the disease and late
      aneurysmal dilation have been considered as indications for intervention. The aim
      of this study is to analyze growth rate patterns of type B dissections based on
      computed tomography (CT) measurements over time. METHODS: We conducted a
      retrospective review of patients with acute type B dissection from 2008 to 2014
      who had at least 2 follow-up CT scans. Patients with rapid progression requiring
      interventions were also included. Using M2S software (M2S, Lebanon, NH), we
      calculated the mean centerline diameter of the true and false lumens at 3
      different sites of the descending aorta. Growth rate was calculated as the change
      in maximal diameter between the first interval and last available CT scans.
      Primary outcome was to compare the growth rate pattern between the 2 time
      intervals. Secondary outcomes included early and delayed aortic intervention and
      overall mortality (OM). RESULTS: A total of 108 patients were included. Average
      age of patients was 58.7 years. Median follow-up time was 3 months for the first
      CT and 32 months for the second. OM was 27.8% (n = 30), whereas the disease
      specific mortality was 11.1% (n = 12). Thirty-seven percent (n = 40) required
      operative intervention (18 open and 22 endovascular repair): 20 at 30 days, 12 at
      12 months, and 8 patients at >1 year. Mean aortic growth rate was higher in the
      first time interval compared with the second: 0.89 vs. 0.19 mm/month (P < 0.05)
      at the proximal descending aorta, 1.01 vs. 0.18 mm/month (P < 0.05) at the mid
      descending aorta, and 0.65 vs. 0.28 mm/month; (P < 0.05) at the distal descending
      aorta. Those who underwent intervention had a higher aortic growth rate at early
      and late interval (P < 0.05). Age and number of comorbidities were associated
      with OM. Thrombosis of the false lumen did not affect the mortality and
      intervention rate. CONCLUSIONS: Type B dissection is associated with aortic
      growth over time. The overall growth rate was not linear with a more prominent
      initial phase. Faster aortic growth rate is associated with an increased
      intervention rate, whereas advanced age and number of comorbidities are
      associated with increased mortality. Prospectively designed studies are needed to
      identify the subgroup of patients who may benefit from early intervention based
      on growth rate measurements.

PMID- 29217444
TI  - Outcome and Complications Using Negative Pressure Wound Therapy in the Groin for
      Perivascular Surgical Site Infections after Vascular Surgery.
AB  - BACKGROUND: The aim of this study was to investigate graft preservation, major
      bleeding, and reinfection rate using negative pressure wound therapy (NPWT) for
      perivascular surgical site infections (SSIs) in the groin after vascular surgery
      and factors associated with failure of treatment. METHODS: Retrospective data
      were collected during 2004-2015. Failure of wound treatment was defined as a
      wound not healed within 4 months, visible graft material or native artery after 1
      month, bleeding from the wound leading to discontinuation of treatment, or death
      or amputation due to the groin infection. RESULTS: The median age of the 161
      patients was 71 years; 63% were men. The rate of graft preservation rate was 81%;
      64% for synthetic grafts. Major bleeding during NPWT occurred in 7.1% and local
      reinfection in 6.4%. Synthetic graft infection (odds ratio [OR] = 6.1, 95%
      confidence interval [CI] = 2.6-14.4) and bleeding/pseudoaneurysm as presenting
      symptom (OR = 2.9, 95% CI = 1.0-8.2) were independently associated with increased
      failure rate of treatment. CONCLUSIONS: NPWT is a good option for perivascular
      SSI in the groin after vascular surgery. Patients with a synthetic graft
      infection and/or presenting with pseudoaneurysm or bleeding may be considered for
      an adjunctive or alternative treatment option.

PMID- 29217445
TI  - Factors that Predict Failure to Meet Merit-Based Incentive Payment System Quality
      Measures for Asymptomatic Carotid Endarterectomy.
AB  - BACKGROUND: The Physician Quality Reporting System (PQRS) created by the Centers
      for Medicare and Medicaid Services financially penalizes providers who fail to
      meet expected quality of care measures. The purpose of this study is to evaluate
      the factors that predict failure to meet PQRS measures for carotid endarterectomy
      (CEA). METHODS: PQRS measure 260 (discharge by postoperative day 2 following CEA
      in asymptomatic patients) and 346 (rate of postoperative stroke or death
      following CEA in asymptomatic patients) were evaluated using hospital records
      from the state of Florida from 2008 to 2012. The impact of demographics,
      comorbidities, hospital factors, admission variables, and individual practitioner
      data upon timely discharge, and postoperative stroke and death. Odds ratios, 95%
      confidence intervals, and significance (P < 0.05) were determined through the
      development of a logistic regression model. Surgeons were identified by national
      provider identifier number, and practitioner data obtained from the American
      Medical Association Physician Masterfile. RESULTS: A total of 34,235 patient
      records and 701 providers were identified over the 5-year period. Significant
      negative predictors for PQRS measure 260 included weekend admission (odds ratio
      [OR], 2.9), Medicaid (OR, 2.4), surgeon historical postoperative stroke rate
      >2.0% (OR, 1.7), African-American race (OR, 2.0), and female gender (OR, 1.3).
      The presence of any of these factors was associated with a 13.5% rate of failure.
      The most significant negative predictor for PQRS measure 346 was surgeon
      postoperative stroke rate >2.0% (OR, 6.2 for stroke and OR, 29.0 for death).
      Surgeons in this underperforming group had worse outcomes compared to their peers
      despite having patients with fewer risk factors for poor outcomes. Surgeon
      specialty, board certification, and case volume do not impact either PQRS
      measures. CONCLUSIONS: Selected groups of patients and surgeons with a
      disproportionately high rate of postoperative stroke are at risk of failing to
      meet PQRS pay for performance quality measures. Awareness of these risk factors
      may help mitigate and minimize the risk of adversely impacting the value stream.
      Further evaluation of the causative factors that lead to surgeon underperformance
      could help to improve the quality of care.

PMID- 29217446
TI  - The Use of the Profunda Femoral Artery as the Sole Target Vessel to Bypass
      Aortoiliac Disease in Patients with Critical Limb Ischemia and Concomitant
      Unreconstructable Infrainguinal Disease.
AB  - BACKGROUND: Critical limb ischemia (CLI) often results from multilevel occlusive
      disease. There are occasions where a patent profunda femoral artery (PFA) is the
      only target artery that can be used as outflow during reconstruction to bypass
      aortoiliac disease (AOID), with no further option for infrainguinal
      revascularization. We aim to report results of the use of PFA as the sole target
      vessel for the treatment of these patients. METHODS: This is a retrospective,
      single-center study including CLI patients treated during 36 months. All
      procedures were included regardless of inflow site. The outcomes examined were
      hemodynamic improvement, clinical status change, amputation-free and overall
      survival, and patency of the prosthesis. Univariate analysis was performed to
      identify possible predictors of adverse outcomes. RESULTS: Twenty-three patients
      and 27 limbs were included (2 female, mean age 70.6). Sixteen limbs presented
      rest pain and 11 tissue loss. Inflow was obtained from the axillary (n = 9),
      contralateral femoral (n = 8), abdominal aorta (n = 2), thoracic aorta (n = 1),
      ipsilateral external iliac (n = 2), and contralateral external iliac artery (n =
      1). Immediately postoperatively ankle-brachial index significantly increased from
      0.15 (0-0.5) to 0.50 (0.25-0.9), (P-value < 0.001). Twenty-four limbs presented
      clinical improvement (3 minimally, 18 moderately, and 3 markedly improved) and 3
      presented no change. During a mean follow-up of 15.8 (2-36) months, we recorded 4
      deaths and 4 major amputations. Mean predicted overall survival and amputation
      free survival were 29.8 (95% confidence interval [CI] 24.5-35.1) and 26.5 months
      (95% CI 21.1-31.8), respectively. Predicted primary patency was 76% at 3 years.
      Univariate analysis revealed significant associations only between bypass patency
      and limp loss (P-value = 0.021). CONCLUSIONS: In the presence of CLI due to AOID
      and unreconstructable infrainguinal disease, the use of PFA as the sole target
      vessel during bypass is associated with significant rates of clinical improvement
      and limb salvage.

PMID- 29217447
TI  - Early Experience with Fenestrated Endovascular Compared to Open Repair of Complex
      Abdominal Aortic Aneurysms in a High-Volume Open Aortic Center.
AB  - BACKGROUND: Early data suggest that fenestrated endovascular aneurysm repair
      (FEVAR) is feasible but may have higher morbidity and unclear durability compared
      to open surgical repair (OSR) of complex abdominal aortic aneurysms (CAAAs). We
      compared the early experience following elective FEVAR to traditional OSR of CAAA
      in a high-volume open aortic center. METHODS: All patients undergoing FEVAR and
      OSR for elective CAAA from 1/2010-7/2015 were identified. Univariate,
      multivariable logistic, and Cox hazards modeling were used to compare
      perioperative and intermediate outcomes. RESULTS: We identified 116 patients who
      underwent CAAA repair (18 FEVAR) with a median follow-up of 26 months. FEVAR
      patients had higher rates of congestive heart failure (22% vs. 5.1%; P = 0.03).
      Operative time was slightly longer following FEVAR (282 vs. 240 min, P = 0.02).
      There was no difference in 30-day operative mortality (0% in both) or major
      complications. Median intensive care unit (0 vs. 3 days; P < 0.001) and hospital
      length of stay (2.5 vs. 7 days; P < 0.001) were shorter after FEVAR. Rates of 30
      day graft complications (5.6% FEVAR vs. 5.1% OSR, P = 1.0) were similar, and
      there was no statistically significant difference in rates of graft complications
      in follow-up (17% vs. 8.2%, P = 0.37). After multivariable modeling, FEVAR
      patients were more likely to develop late graft-related complications (hazard
      ratio [HR]; 5.0, 95% confidence interval [CI]: 0.98-25). Kaplan-Meier 1-year
      survival was similar (100% vs. 92%), even after multivariable adjustment (HR,
      0.6; 95% CI: 0.1-5.0). CONCLUSIONS: Early experience in FEVAR at a high-volume
      open aortic center shows that FEVAR can be performed safely with comparable
      perioperative risk to OSR. FEVAR may be associated with graft complications
      during follow-up, which should be considered in clinical decision-making. Further
      study is warranted to better elucidate late durability of FEVAR and the impact of
      the learning curve on outcomes.

PMID- 29217448
TI  - Perioperative Outcomes after Regional Versus General Anesthesia for Above the
      Knee Amputations.
AB  - BACKGROUND: Nontraumatic lower extremity amputation (LEA) remains a common
      procedure among patients who frequently have significant comorbidities. Patients
      undergoing above knee amputation (AKA) have the highest rates of mortality in
      this cohort, yet there is little evidence to support selection between peripheral
      nerve block or neuraxial regional anesthesia (RA) versus general anesthesia (GA)
      techniques. The objective of this study was to determine whether RA (neuraxial or
      peripheral nerve block) techniques were associated with more favorable outcomes
      versus general anesthesia among patients undergoing AKA. METHODS: This is a
      retrospective cohort study using propensity-matched groups. Patients undergoing
      AKA were identified in the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) data set and grouped according to anesthetic type
      as either RA or GA. Patients undergoing AKA with RA were propensity matched to
      similar patients who had GA. Primary outcome was 30-day mortality. Secondary
      outcomes were numerous and included cardiac, pulmonary, infectious, and bleeding
      complications, as well as length of stay. Among a subset of patients for whom
      readmission data were available, rate of readmission was compared as a secondary
      outcome. RESULTS: Nine thousand nine hundred ninety-nine patients were identified
      in the ACS-NSQIP database. One thousand three hundred twelve received a regional
      anesthetic, and the remainder had a general anesthetic. Factors significantly
      associated with GA included younger age (70 vs. 75 years; P < 0.001), higher body
      mass index (26.5 vs. 25.4; P < 0.001), and ethnically white (62.4% vs. 57%; P <
      0.001). Before matching, patients receiving RA were less likely to be smokers
      (22% vs. 29%; P < 0.001), have a bleeding disorder (15% vs 30%; P < 0.001), or
      have a diagnosis of sepsis (26% vs 34%; P < 0.001). Propensity score matching
      produced a cohort composed of 1,916 patients equally divided between RA and GA.
      We found no difference with respect to the primary end point of 30-day mortality
      (11.7% vs 11.7%; odds ratio [OR] 1.01; P = 0.943) nor was there any difference
      with respect to secondary outcomes. Among patients for whom readmission data were
      available, there was no statistically significant difference between rates of
      readmission between the groups (15.6% for RA vs. 12.7% for GA; OR 1.26,
      confidence interval 0.87-1.828, P = 0.221). CONCLUSIONS: The present
      investigation did not detect any difference between regional and general
      anesthetic with respect to morbidity or mortality among patients undergoing AKA.
      This data set did not allow us to address other relevant markers including pain
      control or phantom limb syndrome.

PMID- 29217449
TI  - Role of Brachial Artery Ligation in Management of Prosthetic Arteriovenous Graft
      Infections.
AB  - BACKGROUND: Arteriovenous graft (AVG) infections can present as major life
      threatening hemorrhage or sepsis in a chronic kidney disease patient. Frequently,
      all these patients present in critical condition which need prompt and
      expeditious management. Various procedures are described for management of
      infected grafts and its bleeding complications. However, these procedures are
      associated with postop-operative bleeding and persistent infection. The aim was
      to study brachial artery ligation (BAL) near the elbow joint in the management of
      an infected AVG. METHODS: It was a retrospective study where data collection was
      done for 51 patients who underwent BAL in infected AVGs from January 2007 to
      December 2016. RESULTS: During the study period, AVG infections were treated in
      62 patients. Fifty-one BALs were done in 62 limbs treated. All were arm grafts
      (brachial artery to axillary vein) using expanded polytetrafluoroethylene grafts.
      In 49 patients, BAL was done as a primary procedure. In 2 patients, BAL was done
      after they presented with uncontrolled infection after initial subtotal excision
      with oversewing of graft stump at arterial anastomosis. There were 36 men and 15
      women, with a mean age of 49 years (range, 23-82). The primary etiologies for
      renal failure were hypertension (56.2%), diabetes (34.3%), and others (9.5%).
      Follow-up was 100% at 1 month and 82.3% (42 patients) at 3 months, and none
      showed any signs of ischemia or sepsis. All had biphasic signals in radial and
      ulnar arteries with normal peripheral capillary oxygen saturation readings in
      fingers. None of the patients underwent additional interventions. CONCLUSIONS:
      BAL in AVG infections is a safe alternative considering the critical general
      condition of chronic kidney disease patient. It reduces the operative time
      significantly and avoids complex revascularization and anastomotic dehiscence
      without any ischemic or bleeding complications. BAL near the elbow joint in
      patients with good back-bleeding can be used as a primary approach in an infected
      AVG. However, close monitoring of patient in postoperative period is essential.

PMID- 29217450
TI  - Cadm2 regulates body weight and energy homeostasis in mice.
AB  - OBJECTIVE: Obesity is strongly linked to genes regulating neuronal signaling and
      function, implicating the central nervous system in the maintenance of body
      weight and energy metabolism. Genome-wide association studies identified
      significant associations between body mass index (BMI) and multiple loci near
      Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling
      enriched in the brain. Here we sought to further understand the role of Cadm2 in
      the pathogenesis of hyperglycemia and weight gain. METHODS: We first analyzed
      Cadm2 expression in the brain of both human subjects and mouse models and
      subsequently characterized a loss-of-function mouse model of Cadm2 for
      alterations in glucose and energy homeostasis. RESULTS: We show that the risk
      variant rs13078960 associates with increased CADM2 expression in the hypothalamus
      of human subjects. Increased Cadm2 expression in several brain regions of
      Lepob/ob mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese
      mice (Cadm2/ob) resulted in reduced adiposity, systemic glucose levels, and
      improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor
      activity, energy expenditure rate, and core body temperature identifying Cadm2 as
      a potent regulator of systemic energy homeostasis. CONCLUSIONS: Together these
      data illustrate that reducing Cadm2 expression can reverse several traits
      associated with the metabolic syndrome including obesity, insulin resistance, and
      impaired glucose homeostasis.

PMID- 29217451
TI  - Between-trial heterogeneity in meta-analyses may be partially explained by
      reported design characteristics.
AB  - OBJECTIVE: We investigated the associations between risk of bias judgments from
      Cochrane reviews for sequence generation, allocation concealment and blinding,
      and between-trial heterogeneity. STUDY DESIGN AND SETTING: Bayesian hierarchical
      models were fitted to binary data from 117 meta-analyses, to estimate the ratio
      lambda by which heterogeneity changes for trials at high/unclear risk of bias
      compared with trials at low risk of bias. We estimated the proportion of between
      trial heterogeneity in each meta-analysis that could be explained by the bias
      associated with specific design characteristics. RESULTS: Univariable analyses
      showed that heterogeneity variances were, on average, increased among trials at
      high/unclear risk of bias for sequence generation (lambda^ 1.14, 95% interval:
      0.57-2.30) and blinding (lambda^ 1.74, 95% interval: 0.85-3.47). Trials at
      high/unclear risk of bias for allocation concealment were on average less
      heterogeneous (lambda^ 0.75, 95% interval: 0.35-1.61). Multivariable analyses
      showed that a median of 37% (95% interval: 0-71%) heterogeneity variance could be
      explained by trials at high/unclear risk of bias for sequence generation,
      allocation concealment, and/or blinding. All 95% intervals for changes in
      heterogeneity were wide and included the null of no difference. CONCLUSION: Our
      interpretation of the results is limited by imprecise estimates. There is some
      indication that between-trial heterogeneity could be partially explained by
      reported design characteristics, and hence adjustment for bias could potentially
      improve accuracy of meta-analysis results.

PMID- 29217452
TI  - Specific agreement on ordinal and multiple nominal outcomes can be calculated for
      more than two raters.
AB  - OBJECTIVE: The concept of specific agreement (SA) has been proposed for
      dichotomous outcomes for two or more raters. We aim to extend this concept for
      variables with more than two ordinal or nominal categories and more than two
      raters. STUDY DESIGN AND SETTING: We used two data sets: four plastic surgeons
      classifying photographs after breast reconstruction on a 5-point ordinal scale
      and six raters classifying psychiatric patients into five diagnostic categories.
      For m raters, all (i.e., m(m-1)/2) pairwise agreement tables were summed to
      calculate the observed agreement (OA), SA and conditional probabilities. The 95%
      confidence intervals were obtained by bootstrapping. RESULTS: SA was calculated
      for each ordinal or nominal category to examine when one of the raters scored in
      a specific category, what is the probability that the other raters scored in that
      same category. And suppose one of the raters scored X1, what is the probability
      that the other raters scored X1 or any of the other categories (conditional
      probability). It appeared, for example, that among the psychiatric disorders,
      depression and personality disorders were often mixed up, whereas neurosis was
      rarely mixed up with schizophrenia. CONCLUSION: The concept of SA for variables
      with ordinal and multiple nominal categories provides relevant clinical
      information. The extension to conditional probabilities of alternative categories
      broadens the clinical application with examining which categories are most often
      mixed up.

PMID- 29217453
TI  - Tumor-Suppressing Effect of Silencing of Annexin A3 Expression in Breast Cancer.
AB  - INTRODUCTION: Annexin A3 (ANXA3) participates in various tumor-associated
      biological processes, including tumor initiation, progression, and metastasis.
      The present study was designed to investigate the expression and function of
      ANXA3 in breast cancer cells. MATERIALS AND METHODS: Annexin A3 protein
      expression in breast cancer cell lines was evaluated using Western blot analysis.
      ANXA3 expression in MDA-MB 231 breast cancer cells was silenced by RNA
      interference, and the effects of RNA silencing on cell proliferation, colony
      forming ability, wound-healing, and invasiveness were evaluated. Levels of ANXA3
      expression in 30 primary breast cancers were assayed using immunohistochemistry
      and correlated with patient survival. RESULTS: Levels of ANXA3 expression were
      higher in the basal subtype of breast cancer cells, such as MDA-MB 231, HCC-70,
      and HCC-1954 cells, than in other subtypes. ANXA3 silencing inhibited the
      activities of MDA-MB 231 and HCC-1954 cells, including their proliferation,
      invasion across transwell membranes, and wound-healing and colony forming
      abilities. ANXA3 small interfering RNA (siRNA) also reduced the expression of
      cycle-dependent kinase protein and increased the expression of E2F1 and p27
      proteins compared with control siRNA. Expression of ANXA3 was closely correlated
      with tumor size, with higher ANXA3 expression associated with reduced disease
      free survival in breast cancer patients. CONCLUSION: These findings indicate that
      ANXA3 is associated with the natural progression of breast cancer and might be a
      potential prognostic marker of patient survival.

PMID- 29217454
TI  - Patient-related barriers to Rigid Gas Permeable (RGP) lens wear among keratoconus
      patients in Jordan.
AB  - PURPOSE: To assess potential patient-related barriers to rigid gas permeable
      (RGP) lens wear for vision rehabilitation in a sample of keratoconus (KC)
      patients in Jordan. METHODS: Barriers for RGP contact lens wear among KC patients
      were discussed and specified by a focus group which consisted of five
      optometrists who are involved in contact lens practice. The focus group addressed
      potential barriers for RGP lens wear from the patient's perspective. The
      identified barriers were then used to design the final questionnaire used in the
      study. The questionnaire consisted of 8 questions which ask the participant to
      rate, within a 5-points scale (1: strongly disagree to 5: strongly agree), how
      each suggested item is considered a barrier for RGP lens wear. RESULTS: 204 KC
      patients (86 females, 118 males) were involved in a semi-structured interview to
      answer the questionnaire. The average age of participants was 30.85 (+/-8.74)
      years old and ranged from 18 to 62 years. The average age of diagnosis of KC (+/
      standard deviation) is 21.96 (+/-7.22) years old with a range of 12-52 years. All
      participants reported that they had never tried RGP lenses for their vision
      rehabilitation; however, other management options were reported such as glasses,
      keratoplasty, collagen cross linking and Intacs. The mean score of total barriers
      to RGP wear was high at 3.8 (+/-0.4) (out of 5). The major identified barriers
      were: lack of awareness of the benefits of RGP lenses, fear of possible lens
      complications, lack of medical insurance and high cost of the lens. CONCLUSIONS:
      The study reveals that several barriers were identified as prevalent.
      Consequently, there is an imperative need to adopt better planning strategies for
      management protocol of KC in order to assure best eye care service for KC
      patients in Jordan.

PMID- 29217455
TI  - A new method to analyse the effect of multifocal contact lenses on visual
      function.
AB  - PURPOSE: Presbyopic contact lens (CL) fittings produce simultaneous vision,
      providing different retinal images that reduce visual quality and wearers'
      satisfaction. The purpose of this study was to develop a new method to isolate
      the multifocality effect of different CL options to manage presbyopia, analysing
      the impact on binocular visual acuity (VA), stereopsis and contrast sensitivity
      (CS) and determining the effect of the use of a yellow filter (YF) on visual
      function. METHODS: A prospective and double-masked randomized pilot study
      involving 20 healthy volunteers was conducted. Four multifocal CLs and monovision
      CLs without far prescription were fitted. All subjects wore their spectacles over
      the CLs to guarantee optimum VA at distance. Binocular VA, stereopsis and CS were
      assessed after 20min of CL wear with or without a YF of 455nm. RESULTS: Binocular
      VA decreased with all multifocal CLs (P<0.05), as did stereopsis (P<0.01). All
      presbyopia correction reduced CS compared with spectacles (P<0.05), except
      aspheric designs, at a frequency of 3 cycles/ degrees  (P>0.06). Using the YF,
      visual function improved; better binocular VA was found with all multifocal CLs
      (statistically significant (P<0.02) with both low-addition designs), and better
      CS was observed at most spatial frequencies (statistically significant (P<0.02)
      at low frequencies with all CLs). CONCLUSIONS: This pilot study proposes a simple
      method to analyse the impact of multifocal CL wear on VA, stereopsis and CS while
      maintaining habitual spectacle correction to assess the patient's short-term
      opinion and help practitioners and patients make a decision during presbyopia
      correction with CL fitting.

PMID- 29217456
TI  - Goblet cell density estimate differences in impression cytology samples varies
      with different magnification of images.
AB  - PURPOSE: To assess the impact of using different microscope magnifications for
      the goblet cell density (GCD) estimates from conjunctival impression cytology
      (CIC) samples from healthy individuals METHODS: In a prospective study, CIC
      specimens were collected from the superior bulbar conjunctiva (12 o'clock, 5mm
      from limbus) of 20 adult subjects (average age 22 years) onto Millicell-CM
      membranes and Giemsa stained. A region from each CIC filter containing reasonably
      high numbers of goblet cells was imaged by light microscopy at a final
      magnification of 400X and then the same region assessed at 200X and then 100X.
      The images were enlarged, the goblet cells marked and counted and GCD values/sq
      mm calculated. RESULTS: The mean GCD estimates at 400X magnification, 200X and
      100X were 644+/-180, 405+/-72 and 365+/-81 cells/sq mm respectively, and these
      values were statistically different (p<0.001). CONCLUSIONS: As a result of non
      uniform distribution, a strategy to select a 400X high power microscope field
      (HPF) that appears to include a moderate number of goblet cells will have a
      probability (by at least 20:1) that the GCD estimates will likely be higher
      compared to those at 200X or 100X, and the probability for higher GCD values is
      at least 15:1 comparing assessments made at 200X to 100X. Investigators should
      use only one magnification, with that of a medium power field (200X final
      magnification) likely being the most useful.

PMID- 29217457
TI  - Focusing on claudin-5: A promising candidate in the regulation of BBB to treat
      ischemic stroke.
AB  - Claudin-5 is a tight junction (TJ) protein in the blood-brain barrier (BBB) that
      has recently attracted increased attention. Numerous studies have demonstrated
      that claudin-5 regulates the integrity and permeability of the BBB. Increased
      claudin-5 expression plays a neuroprotective role in neurological diseases,
      particularly in cerebral ischemic stroke. Moreover, claudin-5 might be a
      potential marker for early hemorrhagic transformation detection in ischemic
      stroke. In light of the distinctive effects of claudin-5 on the nervous system,
      we present the elaborate network of roles that claudin-5 plays in ischemic
      stroke. In this review, we first introduce basic knowledge regarding the BBB and
      the claudin family, the characterization and regulation of claudin-5, and
      association between claudin-5 and other TJ proteins. Subsequently, we describe
      BBB dysfunction and neuron-specific drivers of pathogenesis of ischemic stroke,
      including inflammatory disequilibrium and oxidative stress. Furthermore, we
      summarize promising ischemic stroke treatments that target the BBB via claudin-5,
      including modified rt-PA therapy, pharmacotherapy, hormone treatment, receptor
      targeted therapy, gene therapy, and physical therapy. This review highlights
      recent advances and provides a comprehensive summary of claudin-5 in the
      regulation of the BBB and may be helpful for drug design and clinical therapy for
      treatment of ischemic stroke.

PMID- 29217458
TI  - IMP2 and IMP3 cooperate to promote the metastasis of triple-negative breast
      cancer through destabilization of progesterone receptor.
AB  - Triple-negative breast cancer (TNBC) is one of the most aggressive malignancies
      and is associated with high mortality rates due to the lack of effective
      therapeutic targets. In this study, we demonstrated that insulin-like growth
      factor-II mRNA-binding protein 2 and 3 (IMP2 and IMP3) are specifically
      overexpressed in TNBC and cooperate to promote cell migration and invasion.
      Downregulation of both IMP2 and IMP3 in TNBC cells was found to produce a
      synergistic effect in suppressing cell invasion and invadopodia formation,
      whereas overexpression of IMP2 and IMP3 in luminal subtype cells enhanced
      epithelial-mesenchymal transition and metastasis. We also showed that IMP2 and
      IMP3 are direct targets of microRNA-200a (miR-200a), which is downregulated in
      TNBC. Conversely, IMP2 and IMP3 suppressed the transcription of miR-200a by
      destabilizing progesterone receptor (PR) mRNA through recruitment of the CCR4-NOT
      transcription complex subunit 1 (CNOT1) complex. Together, our findings suggest
      that IMP2 and IMP3 partially determine the characteristic phenotype and
      synergistically promote the metastasis of TNBC by downregulating PR. The
      identified IMP2/3-miR-200a-PR axis represents a novel double-negative feedback
      loop and serves as a new potential therapeutic target for the treatment of TNBC.

PMID- 29217459
TI  - Technical aspects of microphysiological systems (MPS) as a promising wet human-in
      vivo simulator.
AB  - Microphysiological systems (MPS) are currently attracting a lot of interest from
      pharmaceutical companies worldwide. In the United States and European Union,
      several large government projects related to MPS have been initiated, and, in
      Japan, pharmaceutical companies interested in MPS are watching the recent trends
      and developments in the field. In July 2017, the Japan Agency for Medical
      Research and Development initiated a research program to develop chip-based MPS.
      In this review, we examine the technical aspects of commercializing chip-based
      MPS.

PMID- 29217460
TI  - Tissue-specific cellular immune responses to malaria pre-erythrocytic stages.
AB  - Complete and long-lasting protective immunity against malaria can be achieved
      through vaccination with invasive live attenuated Plasmodium sporozoites, the
      motile stage inoculated in the host skin during a mosquito bite. Protective
      immunity relies primarily on effector CD8+ T cells targeting the parasite in the
      liver. Understanding the tissue-specific features of the immune response is
      emerging as a vital requirement for understanding protective immunity. The small
      parasite inoculum, the scarcity of infected cells and the tolerogenic properties
      of the liver represent hurdles for the establishment of protective immunity in
      endemic areas. In this review, we discuss recent advances on liver-specific
      features of immunity including innate recognition of malaria pre-erythrocytic
      stages, CD8+ T cell interactions with infected hepatocytes, antigen presentation
      for effective CD8+ T cell responses and generation of liver-resident memory CD8+
      T cells. A better understanding of the factors involved in the induction and
      maintenance of effector CD8+ T cell immunity against malaria pre-erythrocytic
      stages is crucial for the development of an effective vaccine targeting the
      initial phase of malaria infection.

PMID- 29217461
TI  - The irresponsible promotion of e-cigarettes and Swaptober.

PMID- 29217462
TI  - E-cigarettes: further flavours of controversy within the controversy.

PMID- 29217464
TI  - The relationship between trait psychopathy and emotional intelligence: A meta
      analytic review.
AB  - Psychopathy is a personality construct that has been related to important
      emotional deficits. These findings have led to a growing interest in exploring if
      psychopathic traits are associated with emotional intelligence (EI). However, the
      literature exploring this association has revealed conflicting results. The aim
      of the present study was to provide a reliable estimate of the relationship
      between psychopathy traits and EI (measured as performance-based ability) through
      meta-analysis. A quantitative and systematic review of the literature using
      Scopus, Medline, Pubmed, and PsicINFO showed a total of 13 studies meeting
      inclusion criteria with a combined sample of 2401 participants. The meta-analysis
      revealed a significant negative relationship between both constructs, showing
      that higher psychopathic trait scores are related to lower EI levels. We propose
      several future research lines to clarify possible gaps and ambiguities in the
      current literature and a set of interesting clinical implications for the
      prevention, evaluation, and treatment of psychopathic traits by including EI
      factors in traditional models of psychopathy.

PMID- 29217465
TI  - Heavy precipitation as a risk factor for shigellosis among homeless persons
      during an outbreak - Oregon, 2015-2016.
AB  - OBJECTIVES: Shigella species are the third most common cause of bacterial
      gastroenteritis in the United States. During a Shigella sonnei outbreak in Oregon
      from July 2015 through June 2016, Shigella cases spread among homeless persons
      with onset of the wettest rainy season on record. METHODS: We conducted time
      series analyses using Poisson regression to determine if a temporal association
      between precipitation and shigellosis incidence existed. Models were stratified
      by housing status. RESULTS: Among 105 infections identified, 45 (43%) occurred in
      homeless persons. With increasing precipitation, cases increased among homeless
      persons (relative risk [RR] = 1.36 per inch of precipitation during the exposure
      period; 95% confidence interval [CI] = 1.17-1.59), but not among housed persons
      (RR = 1.04; 95% CI 0.86-1.25). CONCLUSIONS: Heavy precipitation likely
      contributed to shigellosis transmission among homeless persons during this
      outbreak. When heavy precipitation is forecast, organizations working with
      homeless persons could consider taking proactive measures to mitigate spread of
      enteric infections.

PMID- 29217463
TI  - Electrical storm in the early phase of HeartMate(r) II device implantation:
      Incidence, risk factors and prognosis.
AB  - BACKGROUND: Ventricular arrhythmia is common after left ventricular assist device
      (LVAD) implantation, especially in the early postoperative phase (<30 days). AIM:
      To identify the incidence of and risk factors for electrical storm (ES) occurring
      within 30 days of HeartMate(r) II implantation. METHODS: We reviewed data from
      all consecutive patients undergoing HeartMate(r) II device implantation at our
      institution from January 2008 to December 2014. Patient demographic data,
      pharmacotherapies and outcomes were collected. The primary endpoint was
      occurrence of early ES (within 30 days of surgery), defined as three or more
      separate episodes of sustained ventricular arrhythmia within a 24-hour interval,
      requiring appropriate therapy. RESULTS: Forty-three patients (mean age 56.7+/
      11.2 years; 39 men) were included. At HeartMate(r) II implantation, mean left
      ventricular ejection fraction was 20+/-5%, 32 (74.4%) patients had ischaemic
      cardiomyopathy and 31 (72.1%) were implanted with an indication of bridge to
      cardiac transplantation. During follow-up, 12 (27.9%) patients experienced early
      ES after HeartMate(r) II implantation (median delay 9.1+/-7.8 days). Early ES was
      more frequent in larger patients (body surface area 1.99 vs 1.81 m2; P<0.01),
      tended to be associated with previous sustained ventricular tachycardia (50.0% vs
      22.6%; P=0.08), previous implantable cardioverter-defibrillator implantation
      (66.7% vs 38.7%; P=0.09), discontinuation of long-term beta-blocker therapy
      (75.0% vs 45.2%; P=0.08), weaning of adrenergic drugs after the third day (66.7%
      vs 35.5%; P=0.06) and the use of extracorporeal life support (50% vs 22.6%;
      P=0.079), but was not associated with the cardiomyopathy aetiology or the
      indication for assistance. Catheter ventricular tachycardia ablation was
      performed in six (14.0%) patients. Early ES was associated with a significantly
      higher all-cause mortality rate at the 30th day (33.3% vs 6.5%; P=0.02).
      CONCLUSION: ES is a common and pejorative feature in the early postoperative
      period.

PMID- 29217466
TI  - Influence of corticosterone treatment on nestling begging in Florida scrub-jays
      (Aphelocoma coerulescens).
AB  - Altricial young are dependent on adults for protection and food, and they display
      nutritional need by begging to elicit feeding from parents. Begging at high
      levels can be energetically expensive and attract predators; thus, an individual
      must balance its nutritional needs with these potential costs. Further, because a
      parent is limited in the amount of food it can provide, begging can contribute to
      both parent-offspring conflict and sibling-sibling competition. Many extrinsic
      and intrinsic factors may contribute to begging behavior. One intrinsic factor of
      interest is corticosterone (CORT), a metabolic hormone hypothesized to play a
      role in regulating a nestling's begging behavior. We investigated the hypothesis
      that increased exposure to CORT influences nestling begging behavior in an
      altricial species, the Florida scrub-jay (Aphelocoma coerulescens). We treated
      one nestling per treatment nest with a twice-daily dose of exogenous hormone via
      a CORT-injected waxworm, whereas a second individual received a vehicle-injected
      waxworm. We monitored individual nestling and adult behavior at all nests with
      the use of high-definition video cameras on several days during treatment. We
      found no difference in begging rate between CORT fed and vehicle fed nestlings
      within a treatment nest. Further, to determine whether CORT treatment had
      indirect effects on the entire brood, we monitored additional nests, in which
      nestlings were not manipulated. When treatment and controls were compared,
      overall begging rates of nestlings in treatment nests were greater than those in
      control nests. This result suggests that CORT treatment of an individual altered
      its behavior, as well as that of its siblings.

PMID- 29217467
TI  - Why should we measure free 25(OH) vitamin D?
AB  - Vitamin D, either in its D2 or D3 form, is essential for normal human development
      during intrauterine life, kidney function and bone health. Vitamin D deficiency
      has also been linked to cancer development and some autoimmune diseases. Given
      this huge impact of vitamin D on human health, it is important for daily clinical
      practice and clinical research to have reliable tools to judge on the vitamin D
      status. The major circulating form of vitamin D is 25-hydroxyvitamin D (25(OH)D),
      although it is not the most active metabolite, the concentrations of total 25
      hydroxyvitamin D in the serum are currently routinely used in clinical practice
      to assess vitamin D status. In the circulation, vitamin D - like other steroid
      hormones - is bound tightly to a special carrier - vitamin D-binding protein
      (DBP). Smaller amounts are bound to blood proteins - albumin and lipoproteins.
      Only very tiny amounts of the total vitamin D are free and potentially
      biologically active. Currently used vitamin D assays do not distinguish between
      the three forms of vitamin D - DBP-bound vitamin D, albumin-bound vitamin D and
      free, biologically active vitamin D. Diseases or conditions that affect the
      synthesis of DBP or albumin thus have a huge impact on the amount of circulating
      total vitamin D. DBP and albumin are synthesized in the liver, hence all patients
      with an impairment of liver function have alterations in their total vitamin D
      blood concentrations, while free vitamin D levels remain mostly constant. Sex
      steroids, in particular estrogens, stimulate the synthesis of DBP. This explains
      why total vitamin D concentrations are higher during pregnancy as compared to non
      pregnant women, while the concentrations of free vitamin D remain similar in both
      groups of women. The vitamin D-DBP as well as vitamin D-albumin complexes are
      filtered through the glomeruli and re-uptaken by megalin in the proximal tubule.
      Therefore, all acute and chronic kidney diseases that are characterized by a
      tubular damage, are associated with a loss of vitamin D-DBP complexes in the
      urine. Finally, the gene encoding DBP protein is highly polymorphic in different
      human racial groups. In the current review, we will discuss how liver function,
      estrogens, kidney function and the genetic background might influence total
      circulating vitamin D levels and will discuss what vitamin D metabolite is more
      appropriate to measure under these conditions: free vitamin D or total vitamin D.

PMID- 29217469
TI  - DEM based computational model to predict moisture induced cohesion in
      pharmaceutical powders.
AB  - Pharmaceutical powder flow can alter significantly based on the exposed humidity
      conditions, and lack of computational models to predict the same may undermine
      process development, optimization, and scale-up performances. A Discrete Element
      Model (DEM) is proposed to predict the effects of humidity on pharmaceutical
      powder flow by altering the cohesive forces based on granular bond numbers in
      simple hopper geometries. Experiments analogous to the simulations are further
      performed for three commonly used pharmaceutical excipients at 20%, 40% and 60%
      RH. The equivalent DEM based bond numbers to predict the powder flow tendencies
      are in good accordance with the experimental results and can be a useful tool to
      predict the outcomes of different pharmaceutical processing techniques at various
      humidity conditions.

PMID- 29217468
TI  - Availability of hepatitis C diagnostics and therapeutics in European and Eurasia
      countries.
AB  - BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided
      sustained virological response rates in >95% of patients with chronic hepatitis C
      virus (HCV) infection. However treatment is costly and market access,
      reimbursement and governmental restrictions differ among countries. We aimed to
      analyze these differences among European and Eurasian countries. METHODS: A
      survey including 20-item questionnaire was sent to experts in viral hepatitis.
      Countries were evaluated according to their income categories by the World Bank
      stratification. RESULTS: Experts from 26 countries responded to the survey. As of
      May 2016, HCV prevalence was reported as low (<=1%) in Croatia, Czech Republic,
      Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain,
      Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy,
      Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%).
      All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia,
      and UK. Transient elastography was available in all countries, but reimbursed in
      61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the
      countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia,
      and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or
      another DAA was available. In Germany and the Netherlands all DAAs were
      reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free
      of charge in Georgia. CONCLUSION: Prevalence of HCV is relatively higher in lower
      middle and upper-middle income countries. DAAs are not available or reimbursed in
      many Eurasia and European countries. Effective screening and access to care are
      essential for reducing liver-related morbidity and mortality.

PMID- 29217470
TI  - Safe and effective interferon-beta gene therapy for the treatment of multiple
      sclerosis by regulating biological activity through the design of interferon-beta
      galectin-9 fusion proteins.
AB  - Multiple sclerosis (MS) is the most common demyelinating disease. Despite the
      historical use of interferon-beta (IFN-beta) for the treatment of patients with
      MS, concerns exist regarding the side effects of IFN-beta. In this study, we
      designed a series of novel IFN-beta fusion proteins containing galectin-9 (gal
      9), which exerts immunosuppressive effects through the binding to its receptor on
      activated Th1 cells. We hypothesized that these fusion proteins would improve the
      therapeutic effects and reduce the side effects of IFN-beta. The IFN-beta-gal-9
      fusion proteins showed less IFN-beta biological activity on non-T cells than IFN
      beta alone. In vitro experiments using re-stimulated T cells isolated from mice
      with experimental autoimmune encephalomyelitis (EAE) showed that the IFN-beta-gal
      9 fusion proteins suppressed activated T cells more effectively than IFN-beta.
      Moreover, in our in vivo experiments, the gene transfer of IFN-beta-gal-9 fusion
      protein-expressing plasmid DNA into EAE mice showed beneficial therapeutic
      effects without cytopenia, a known side effect of IFN-beta. In contrast, the gene
      transfer of IFN-beta-expressing plasmid DNA induced a rapid decrease in the white
      blood cell count, despite its therapeutic effect. These results indicate that
      gene therapy using IFN-beta-gal-9 fusion proteins is expected to be safe and
      effective for the treatment of MS.

PMID- 29217471
TI  - 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.
AB  - It was the aim of this study to develop high drug loaded (>30%, w/w),
      thermoplastic polyurethane (TPU)-based dosage forms via fused deposition
      modelling (FDM). Model drugs with different particle size and aqueous solubility
      were pre-processed in combination with diverse TPU grades via hot melt extrusion
      (HME) into filaments with a diameter of 1.75 +/- 0.05 mm. Subsequently, TPU-based
      filaments which featured acceptable quality attributes (i.e. consistent filament
      diameter, smooth surface morphology and good mechanical properties) were printed
      into tablets. The sustained release potential of the 3D printed dosage forms was
      tested in vitro. Moreover, the impact of printing parameters on the in vitro drug
      release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine
      drug powder without observing severe shark skinning or inconsistent filament
      diameter. During 3D printing experiments, HME filaments based on hard TPU grades
      were successfully converted into personalized dosage forms containing a high
      concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics
      were mainly affected by the matrix composition and tablet infill degree.
      Therefore, this study clearly demonstrated that TPU-based FDM feedstock material
      offers a lot of formulation freedom for the development of personalized dosage
      forms.

PMID- 29217472
TI  - Performance indicators for carrier-based DPIs: Carrier surface properties for
      capsule filling and API properties for in vitro aerosolisation.
AB  - This study investigates engineered carrier, as well as engineered API particles,
      and shows that there are distinct performance indicators of particle engineering
      for carrier-based dry powder inhalers (DPIs). Spray dried (SDSS) and jet-milled
      (JMSS) salbutamol sulphate (SS) was blended with untreated alpha-lactose
      monohydrate (LAC_R) and alpha-lactose monohydrate engineered (LAC_E). Subsequent
      capsule filling was performed with different process settings on a dosator nozzle
      capsule filling machine in order to reach a target fill weight of 20-25 mg. To
      evaluate the performance of the different mixtures, in vitro lung deposition
      experiments were carried out with a next generation impactor, the emitted dose
      (ED) and fine particle fraction (FPF) were calculated based on the specification
      of the European pharmacopoeia. The FPF of micronised powder blends is
      significantly higher (20%) compared to the FPF of spray dried blends (5%).
      Compared to API engineering, carrier engineering had a positive effect on the
      capsule filling performance (weight variability and mean fill weight) at lower
      compression ratios (setting 1). Results further showed that higher compression
      ratios appear to be beneficial in terms of capsule filling performance (higher
      fill weight and less fill weight variation). Concluding, it can be stated that
      the carrier engineering, or generally carrier properties, govern downstream
      processing, whereas the API engineering and API properties govern the
      aerosolisation performance and thereby significantly affect the dose delivery to
      the lungs.

PMID- 29217473
TI  - Impact of digestion on the transport of dextran-loaded self-emulsified
      nanoemulsion through MDCK epithelial cell monolayer and rat intestines.
AB  - Many of the lipids and surfactants used to prepare the self-emulsified
      nanoemulsion (SEN) are subjected to the gastro-intestinal enzymatic digestion,
      which may affect the absorption of the loaded drug. The present study was to
      investigate the impact of such digestion on the transport of hydrophilic
      macromolecules (10-kDa dextran as the model compound) loaded in SEN through the
      MDCK cell monolayer and ex-vivo rat intestines. FITC-labeled dextran (FD) was
      loaded inside the inner oil phase of SEN by the formation of FD-phospholipid
      solid dispersion (FDPS). After digestion, the droplet size increased from 31.06
      +/- 2.10 nm to 494.6 +/- 22.1 nm, and the FD content in the external aqueous
      phase increased from 41.6 +/- 4.2% to 61.1 +/- 4.4%. Compared to the FD solution,
      SEN without digestion enhanced the transport of FD through MDCK cell monolayer
      4.1 times and through rat intestines 3.0-7.4 times. However, the digestion
      reduced the transport of FD 3.5 times through MDCK cell monolayer and 1.3-2.0
      times through rat intestines, compared to that without digestion. This reduction
      was due to the destruction of lipid nano-droplets and release of FD to the
      external aqueous phase of SEN. This finding should be considered when SEN is used
      as a delivery system for hydrophilic macromolecules.

PMID- 29217474
TI  - Effect of particle size, polydispersity and polymer degradation on progesterone
      release from PLGA microparticles: Experimental and mathematical modeling.
AB  - Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were
      prepared by the solvent extraction/evaporation and microfluidic techniques.
      Microparticles were characterized by their size distribution, encapsulation
      efficiency, morphology and thermal properties. The effect of particle size,
      polydispersity and polymer degradation on the in vitro release of the hormone was
      studied. A triphasic release profile was observed for larger microparticles,
      while smaller microspheres showed a biphasic release profile. This behavior is
      related to the fact that complete drug release was achieved in a few days for
      smaller microparticles, during which polymer degradation effects are still
      negligible. A mathematical model was developed that predicts the progesterone
      release profiles from different-sized PLGA microspheres. The model takes into
      account both the dissolution and diffusion of the drug in the polymeric matrix as
      well as the autocatalytic effect of polymer degradation. The model was adjusted
      and validated with novel experimental data. Simulation results are in very good
      agreement with experimental results.

PMID- 29217475
TI  - In vitro drug release and in vivo safety of vitamin E and cysteamine loaded
      contact lenses.
AB  - Cystinosis is an orphan disease caused by a genetic mutation that leads to
      deposition of cystine crystals in many organs including cornea. Ophthalmic
      manifestation of the disease can be treated with hourly instillation of
      cysteamine eye drops. The hourly eye drop instillation is tedious to the patients
      leading to poor compliance and additionally, significant degradation of the drug
      occurs within one week of opening the bottle, which further complicates this
      delivery approach. This paper focuses on designing a contact lens to treat the
      disease with improved efficacy compared to eye drops, and also exploring safety
      of the drug eluding contact lens in an animal model. Our goal is to design a lens
      that is safe and that can deliver a daily therapeutic dose of cysteamine to the
      cornea while retaining drug stability. We show that cysteamine diffuses out
      rapidly from all lenses due to its small size. Vitamin E incorporation increases
      the release duration of both ACUVUE(r)OASYS(r) and ACUVUE(r) TruEyeTM but the
      effect is more pronounced in TruEyeTM likely due to the low solubility of vitamin
      E in the lens matrix and higher aspect ratio of the barriers. The barriers are
      not effective in hydrogel lenses, which along with the high aspect ratio in
      silicone hydrogels suggests that barriers could be forming at the interface of
      the silicone and hydrogel phases. The presence of vitamin E has an additional
      beneficial effect of reduction in the oxidation rates, likely due to a transport
      barrier between the oxygen diffusing through the silicone channels and drug
      located in the hydrogel phase. Based on this study, both Acuvue(r)OASYS(r) and
      ACUVUE(r) TruEyeTM can be loaded with vitamin E to design a cysteamine eluting
      contact lenses for effective therapy of cystinosis. The lenses must be worn for
      about 4-5 hr. each day, which is less than the typical duration of daily-wear.
      The vitamin E and cysteamine loaded lenses did not exhibit any toxicity in a
      rabbit model over a period of 7-days.

PMID- 29217476
TI  - SUMO1 impact on Alzheimer disease pathology in an amyloid-depositing mouse model.
AB  - Small ubiquitin-related modifiers (SUMOs) conjugated or bound to target proteins
      can affect protein trafficking, processing and solubility. SUMOylation has been
      suggested to play a role in the amyloid plaque and neurofibrillary tangle
      pathology of Alzheimer disease (AD) and related neurodegenerative diseases. The
      current study examines the impact of SUMO1 on processing of the amyloid precursor
      protein (APP) leading to the production and deposition of the amyloid-beta
      (Abeta) peptide. An in vivo model of these pathways was developed by the
      generation of double transgenic mice over-expressing human SUMO1 and a mutant
      APP. The SUMO1-APP transgenics displayed normal APP processing but, at later
      ages, exhibited increased insoluble Abeta and plaque density accompanied by
      increased dendritic spine loss, more pronounced synaptic and cognitive deficits.
      These findings suggest a potential impairment in Abeta clearance as opposed to
      increased amyloid production. Examination of microglia indicated a reduction in
      the SUMO1-APP transgenics which is a possible mechanism for the SUMO1-mediated
      increase in amyloid load. These findings suggest an indirect activity of SUMO1
      possibly in the removal of Abeta plaques rather than a direct impact on amyloid
      generation.

PMID- 29217478
TI  - Identification of a gene encoding a flavoprotein involved in bile acid metabolism
      by the human gut bacterium Clostridium scindens ATCC 35704.
AB  - BACKGROUND: The multi-step bile acid 7alpha-dehydroxylating pathway by which a
      few species of Clostridium convert host primary bile acids to toxic secondary
      bile acids is of great importance to gut microbiome structure and host physiology
      and disease. While genes in the oxidative arm of the 7alpha-dehydroxylating
      pathway have been identified, genes in the reductive arm of the pathway are still
      obscure. METHODS: We identified a candidate flavoprotein-encoding gene predicted
      to metabolize steroids. This gene was cloned and overexpressed in E. coli and
      affinity purified. Reaction substrate and product were separated by thin layer
      chromatography and identified by liquid chromatograph mass spectrometry-ion trap
      time of flight (LCMS-IT-TOF). Phylogenetic analysis of the amino acid sequence
      was performed. RESULTS: We report the identification of a gene encoding a
      flavoprotein (EDS08212.1) involved in secondary bile acid metabolism by
      Clostridium scindens ATCC 35704 and related species. Purified rEDS08212.1
      catalyzed formation of a product from 3-dehydro-deoxycholic acid that UPLC-IT-TOF
      MS analysis suggests loses 4amu. Our phylogeny identified this gene in other bile
      acid 7alpha-dehydroxylating bacteria. CONCLUSIONS: These data suggest formation
      of a product, 3-dehydro-4,6-deoxycholic acid, a recognized intermediate in the
      reductive arm of bile acid 7alpha-dehydroxylation pathway and the first report of
      a gene in the reductive arm of the bile acid 7alpha-dehydroxylating pathway.

PMID- 29217477
TI  - Activation of hepatic Nogo-B receptor expression-A new anti-liver steatosis
      mechanism of statins.
AB  - Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X
      receptor alpha (LXRalpha) in an adenosine monophosphate-activated protein kinase
      alpha (AMPKalpha)-dependent manner, thereby inducing severe hepatic lipid
      accumulation and hypertriglyceridemia. Statins have been demonstrated non
      cholesterol lowering effects including anti-nonalcoholic fatty liver disease
      (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on
      activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or
      NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)
      increased triglyceride levels in liver and serum. In vitro, statins reduced lipid
      accumulation in nonsilencing small hairpin RNA-transfected (shNSi), but not in
      NgBR small hairpin RNA-transfected (shNgBRi) HepG2 cells. Inhibition of cellular
      lipid accumulation by atorvastatin is related to activation of AMPKalpha, and
      inactivation of LXRalpha and lipogenic genes. Statin also inhibited expression of
      oxysterol producing enzymes. Associated with changes of hepatic lipid levels by
      WD or atorvastatin, NgBR expression was inversely regulated. At cellular levels,
      statins increased NgBR mRNA and protein expression, and NgBR protein stability.
      In contrast to reduced cellular cholesterol levels by statin or beta
      cyclodextrin, increased cellular cholesterol levels decreased NgBR expression
      suggesting cholesterol or its synthesis intermediates inhibit NgBR expression.
      Indeed, mevalonate, geranylgeraniol or geranylgeranyl pyrophosphate, but not
      farnesyl pyrophosphate or farnesol, blocked atorvastatin-induced NgBR expression.
      Furthermore, we determined that induction of hepatic NgBR expression by
      atorvastatin mainly depended on inactivation of extracellular signal-regulated
      kinases 1/2 (ERK1/2) and protein kinase B (Akt). Taken together, our study
      demonstrates that statins inhibit NAFLD mainly through activation of NgBR
      expression.

PMID- 29217479
TI  - Distinct lipidomic profiles in models of physiological and pathological cardiac
      remodeling, and potential therapeutic strategies.
AB  - Cardiac myocyte membranes contain lipids which remodel dramatically in response
      to heart growth and remodeling. Lipid species have both structural and functional
      roles. Physiological and pathological cardiac remodeling have very distinct
      phenotypes, and the identification of molecular differences represent avenues for
      therapeutic interventions. Whether the abundance of specific lipid classes is
      different in physiological and pathological models was largely unknown. The aim
      of this study was to determine whether distinct lipids are regulated in settings
      of physiological and pathological remodeling, and if so, whether modulation of
      differentially regulated lipids could modulate heart size and function. Lipidomic
      profiling was performed on cardiac-specific transgenic mice with 1) physiological
      cardiac hypertrophy due to increased Insulin-like Growth Factor 1 (IGF1) receptor
      or Phosphoinositide 3-Kinase (PI3K) signaling, 2) small hearts due to depressed
      PI3K signaling (dnPI3K), and 3) failing hearts due to dilated cardiomyopathy
      (DCM). In hearts of dnPI3K and DCM mice, several phospholipids (plasmalogens)
      were decreased and sphingolipids increased compared to mice with physiological
      hypertrophy. To assess whether restoration of plasmalogens could restore heart
      size or cardiac function, dnPI3K and DCM mice were administered batyl alcohol
      (BA; precursor to plasmalogen biosynthesis) in the diet for 16weeks. BA
      supplementation increased a major plasmalogen species (p18:0) in the heart but
      had no effect on heart size or function. This may be due to the concurrent
      reduction in other plasmalogen species (p16:0 and p18:1) with BA. Here we show
      that lipid species are differentially regulated in settings of physiological and
      pathological remodeling. Restoration of lipid species in the failing heart
      warrants further examination.

PMID- 29217480
TI  - Delphinidin protects colon carcinoma cells against the genotoxic effects of the
      mycotoxin altertoxin II.
AB  - Alternaria spp. are ubiquitous molds that are able to produce toxic secondary
      metabolites which may contaminate food globally. One of those is the mycotoxin
      altertoxin II (ATX-II), a genotoxic and mutagenic compound. In recent years,
      different flavonoids that may co-occur with mycotoxins in food were demonstrated
      to temper toxic effects of molds, mostly through their anti-oxidant properties.
      Thus, in this study, we assessed the influence of the berry anthocyanidin
      delphinidin on the toxicity of ATX-II in HT-29 colon carcinoma cells. We
      performed coupled SRB/WST-1 cytotoxicity assays which revealed only weak
      antagonistic interactions, and single-cell gel electrophoresis ("comet") assays,
      where we observed a potent protective effect of delphinidin on the DNA-damaging
      properties of ATX-II. Furthermore, we investigated the mechanism for this
      interaction. In the DCF assay delphinidin was found to reduce intracellular
      oxidative stress levels, which might contribute partly to the latter protection.
      However, LC-MS experiments showed that co-incubation of the mycotoxin with either
      delphinidin or its potential degradation product phloroglucinol aldehyde
      significantly decreased ATX-II concentrations in aqueous solutions, indicating
      that a direct chemical reaction of ATX-II with these components is likely
      responsible for the observed loss of toxicity. Our results indicate that
      delphinidin - and possibly other anthocyanins as well - might play a role in the
      protection of the gut from Alternaria-induced genotoxicity.

PMID- 29217481
TI  - DNA damage and repair proteins in cellular response to sulfur mustard in Iranian
      veterans more than two decades after exposure.
AB  - Delayed effects of sulfur mustard (SM) exposure on the levels of five important
      damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq
      war and 35 unexposed controls. A major DNA damage biomarker protein -
      phosphorylated H2AX - along with four DNA repair proteins in cell response to the
      genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes
      from the veterans and controls using western blotting. Mean levels of XPA, MRE11,
      RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was
      significant. Even though the raised level of phosphor-H2AX in SM-poisoned group
      compared to the controls was not significant it was consistent with DNA damage
      findings confirming the severity of damage to the DNA after exposure to SM. There
      were correlations between the values of RAD51 and NBS1 proteins as well as XPA
      and MRE11 proteins. More than two decades after exposure to SM, there is still
      evidences of DNA damage as well as impaired repair mechanisms in cells of exposed
      individuals. Such disorders in cellular level may contribute to long term health
      problems of the SM veterans.

PMID- 29217482
TI  - Keep Alert Eyes on Delayed Paraplegia.

PMID- 29217483
TI  - In vivo measurement of the rate constant of liver handling of glucose and glucose
      uptake by insulin-dependent tissues, using a mathematical model for glucose
      homeostasis in diabetic rats.
AB  - Diabetes mellitus is a disease that affects glucose homeostasis. The World Health
      Organization informs that there are over 347 million people in the world with
      diabetes. The diagnosis and characterization of glucose homeostasis in different
      metabolic conditions are subjects of great importance with high clinical impact.
      There are many mathematical models that describe the glucoregulatory system in
      detail. However, the use of these models is limited because they have a large
      number of mathematical equations and parameters and they require complex
      methodologies to estimate of them. This forced to work with average values that
      decrease the validity of results and the applicability of the models. In this
      study two mathematical models for rats with diabetes mellitus were developed. The
      difference between these models and others lies in the possibility of obtaining
      all parameters for each animal from simple measurements (glucose and insulin
      plasma levels). Moreover, the models allow to measure in vivo the different
      physiological processes involved in glucose homeostasis in animals: insulin
      secretion and its plasma clearance, absorption of insulin from a subcutaneous
      injection, the liver handling of glucose, intestine absorption of glucose,
      glucose uptake rate of insulin-independent tissues, glucose uptake rate of
      insulin-dependent tissues, and renal glucose excretion.

PMID- 29217484
TI  - The impact of protein interaction networks' characteristics on computational
      complex detection methods.
AB  - Protein complexes of physically interacting proteins play an important role in
      organizing various biological processes in the cell. Therefore, correctly
      identifying complexes is useful for deciphering the cellular mechanisms
      underlying many biological processes. Since the existing high-throughput
      techniques have produced a large amount of protein interactions, computational
      methods are useful complements to the experimental methods for detecting protein
      complexes. In this paper, we analyze six protein interaction networks widely used
      for protein complex detection, and compare the performance of six classic
      computational methods on them in order to find the impacts of network
      characteristics on the performances of these complex detection methods.
      Furthermore, we change topological characteristics of six protein interaction
      networks, and verify the findings by testing performances of six methods on new
      ones. We hope our study will not only help recognize the relations between
      characteristics of protein interaction networks and computational complex
      detection methods, but also provide valuable insight to improve the performance
      in protein complex detection area.

PMID- 29217485
TI  - Developmental origins of adult health and disease: The metabolic role of BDNF
      from early life to adulthood.
AB  - Accumulating evidence suggests that the origins of adult disease may occur during
      fetal life. Thus, the concept of "developmental programming" has been introduced
      and supported by epidemiological and experimental data. This concept supports the
      idea that the nutritional and hormonal status during pregnancy could interfere in
      metabolism control. The mechanisms responsible for this "developmental
      programming" remain poorly documented. Current research indicates that
      neurotrophins and particularly brain-derived neurotrophic factor (BDNF) may play
      a crucial role in this process. Although mainly expressed in the nervous system,
      BDNF and its receptor, tropomyosin-related kinase B (TrkB), are immunolocalized
      in several regions of the human placenta and have important functions during
      pregnancy. BDNF serves widespread roles in regulating energy homeostasis in both
      fetuses and adults, by controlling patterns of fetal growth, adult feeding and
      physical activity, and by regulating glucose metabolism in peripheral tissues.
      Impaired BDNF signaling may be implicated in the etiopathogenesis of the
      metabolic syndrome. Novel BDNF-focused interventions are being developed for
      obesity, diabetes and neurological disorders. The aim of this article is to
      provide a brief comprehensive literary review regarding the potential
      implications of BDNF in "developmental programming", through regulation of
      metabolism and energy balance from early life to adulthood.

PMID- 29217486
TI  - Aberrant promoter methylation in genes related to hematopoietic malignancy in
      workers exposed to a VOC mixture.
AB  - Occupational exposure to volatile organic compounds (VOCs) may cause
      hematopoietic malignancy, either by single exposure to benzene or possibly due to
      a concomitant exposure to several VOCs. Since oxidative stress, inflammation and
      DNA repair pathways are closely involved in cancer development, the effect of VOC
      exposure on expression of proteins involved in these pathways has been studied,
      but epigenetic changes have not been well described. Here, DNA methylation status
      following occupational exposure to a VOC mixture was assessed by bisulfite
      sequencing of the promoter regions of seven genes involved in the mentioned
      pathways. Peripheral blood samples and individual-level VOC exposure data were
      obtained from healthy leather shoe factory workers (LS, n=40) and gas station
      attendants (GS, n=36), as well as a reference group of university employees (C,
      n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane,
      toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels
      were higher in GS (p<0.001). TOP2A, SOD1, and TNF-alpha promoter methylation
      status was increased in LS (p<0.05). In LS, we also found significant
      correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008)
      and COX-2 (r=-0.38, p=0.007) methylation. In exposed groups, ethylbenzene
      exposure levels showed a significant correlation with TOP2A methylation
      (beta=0.33). Our results show early, toxic effects at the epigenetic level caused
      by occupational exposure to high levels of a VOC mixture. These subcellular
      modifications may represent the initial mechanism of toxicity leading to
      hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of
      VOC mixtures.

PMID- 29217487
TI  - Genistein and daidzein treatments differently affect uterine homeostasis in the
      ovary-intact middle-aged rats.
AB  - This study aimed to investigate the effects of soy isoflavones, genistein (GEN)
      and daidzein, (DAI) on the uterine function in ovary-intact middle-aged rats. GEN
      and DAI (35mg/kg) were subcutaneously administrated to acyclic (12-month-old)
      Wistar females, daily, for 4weeks. Control group received either vehicle (olive
      oil and ethanol, 9:1) or remained intact. We found that GEN and DAI differently
      affect uterine morphophysiology. GEN significantly increased the uterine wet
      weight which was associated with hyperplastic changes, revealed by stereological
      and histomorphometrical analyses. Also, PCNA immunoexpression was increased,
      whereas expression of apoptotic marker (caspase-3) was decreased. Protein and
      gene expressions of ERalpha were down-regulated, while PR and ERbeta were up
      regulated after GEN application. Also, GEN caused an increase of LAC and VEGF
      mRNA expression, together with an up-regulation of Akt activity. In contrast, DAI
      did not change the uterine wet weight and stereological features of the main
      uterine compartments as well as LAC and VEGF gene expression. Absence of
      hyperplastic changes were illustrated by an increase in caspase-3
      immunoexpression, associated with reduced PCNA expression. DAI up-regulated only
      the expression of ERbeta, while the expression levels of ERalpha and PR remain
      unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of
      phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did
      not promote events associated with the endometrial cell proliferation in the
      conducted study, figuring as the compound with a potential safety profile, which
      justifies further investigation.

PMID- 29217488
TI  - Incomplete concordance of dopamine transporter Cre (DATIREScre)-mediated
      recombination and tyrosine hydroxylase immunoreactivity in the mouse forebrain.
AB  - Co-localization of the expression of the dopamine transporter (DAT) with the
      catecholamine synthesising enzyme tyrosine hydroxylase (TH) has been investigated
      using transgenic mice expressing Cre recombinase (Cre) dependent green
      fluorescent protein (GFP) under the control of the DAT promoter (DATIREScre/GFP).
      Brain sections from adult female mice were stained for Cre-induced GFP and TH
      using immunohistochemistry, revealing a high degree of co-expression in the
      midbrain dopaminergic neurons (A8-10) with the exception of the periaqueductal
      and dorsal raphe nuclei where dual-labelling was notably lower. In contrast, most
      of the rostral groups of TH-expressing neurons in the forebrain (A11, A13 - A15)
      showed little or no co-localization with Cre-induced GFP. Interestingly, a
      subpopulation of about 30% of the TH-immunoreactive neurons in the arcuate
      nucleus (A12) also express GFP staining. This observation supports the proposal
      that this hypothalamic cluster of dopaminergic neurons is neurochemically, and
      thus potentially functionally, heterogeneous. This study extends earlier
      literature focusing primarily on DAT expression in midbrain structures to
      demonstrate a heterogeneity of DAT and TH co-localization in forebrain neurons,
      particularly those in the hypothalamus. It also highlights the importance of
      carefully selecting and validating transgenic mouse lines when studying
      dopaminergic neurons.

PMID- 29217489
TI  - Fixed volume particle trace emission for the analysis of left atrial blood flow
      using 4D Flow MRI.
AB  - 4D Flow MRI has been used to quantify normal and deranged left ventricular blood
      flow characteristics on the basis of functionally distinct flow components.
      However, the application of this technique to the atria is challenging due to the
      presence of continuous inflow. This continuous inflow necessitates plane-based
      emission of particle traces from the inlet veins, leading to particles that
      represents different amounts of blood, and related quantification errors. The
      purpose of this study was to develop a novel fixed-volume approach for particle
      tracing and employ this method to develop quantitative analysis of 4D blood flow
      characteristics in the left atrium. 4D Flow MRI data were acquired during free
      breathing using a navigator-gated gradient-echo sequence in three volunteers at
      1.5T. Fixed-volume particle traces emitted from the pulmonary veins were used to
      visualize left atrial blood flow and to quantitatively separate the flow into two
      functionally distinct flow components: Direct flow=particle traces that enter and
      leave the atrium in one heartbeat, Retained flow=particle traces that enter the
      atrium and remains there for one cardiac cycle. Flow visualization based on fixed
      volume traces revealed that, beginning in early ventricular systole, flow enters
      the atrium and engages with residual blood volume to form a vortex. In early
      diastole during early ventricular filling, the organized vortical flow is
      extinguished, followed by formation of a second transient atrial vortex. Finally,
      in late diastole during atrial contraction, a second acceleration of blood into
      the ventricle is seen. The direct and retained left atrial flow components were
      between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion,
      fixed-volume particle tracing permits separation of left atrial blood flow into
      different components based on the transit of blood through the atrium.

PMID- 29217490
TI  - Evaluation of pancreatic exocrine insufficiency by cine-dynamic MRCP using
      spatially selective inversion-recovery (IR) pulse: Correlation with severity of
      chronic pancreatitis based on morphological changes of pancreatic duct.
AB  - PURPOSE: To evaluate the correlation between the pancreatic exocrine
      insufficiency estimated by cine-dynamic MRCP using spatially selective IR pulse
      and the severity stages (modified Cambridge classification) based on
      morphological changes of the pancreatic duct in patients with suspected chronic
      pancreatitis. MATERIALS AND METHODS: Thirty-nine patients with suspected chronic
      pancreatitis underwent cine-dynamic MRCP with a spatially selective IR pulse. The
      secretion grading score (5-point scale) based on the moving distance of
      pancreatic juice inflow on cine-dynamic MRCP was assessed, and compared with the
      stage of the severity of chronic pancreatitis based on morphological changes of
      pancreatic duct. RESULT: The stage of the severity of chronic pancreatitis based
      on morphological changes had significant negative correlations with the secretion
      grade (r=-0.698, P<0.001). The secretion grading score of stage 4 was
      significantly lower than stage 1-3 (P<0.001, P=0.002, P=0.025, respectively). In
      all 19 patients in stage 4, the secretion grading score was <0.70. The secretion
      grading score of stage 1 was significantly higher than stage 2 and 4 (P=0.019,
      P<0.001, respectively). In stage 2, the secretion grading score was <0.70 in 8
      (89%) of 9 patients showing pancreatic exocrine insufficiency. Conversely, in
      stage 3, the secretion grading score was >0.70 in 2 (33%) of 6 patients showing
      normal pancreatic exocrine function. CONCLUSION: It should be noted that the
      degree of morphological changes of pancreatic duct does not necessarily reflect
      the severity of pancreatic exocrine insufficiency at cine-dynamic MRCP in stage 2
      3 chronic pancreatitis.

PMID- 29217491
TI  - Intravoxel incoherent motion diffusion-weighted imaging for the assessment of
      renal fibrosis of chronic kidney disease: A preliminary study.
AB  - PURPOSE: To investigate the potential of Intravoxel incoherent motion diffusion
      weighted imaging(IVIM-DWI) for the assessment of renal fibrosis in chronic kidney
      disease (CKD), using histopathology as a reference standard. METHODS: Eighty-five
      CKD patients and twenty healthy volunteers were recruited in this study. IVIM-DWI
      was performed in all of the participants, and all of the CKD patients underwent
      renal biopsy. The mean values of the true diffusion coefficient (D), pseudo
      diffusion coefficient (D*) and perfusion fraction (f) in the renal cortex and
      medulla were compared between the CKD patients and healthy volunteers. The
      Spearman correlation coefficient was calculated to assess the relationship
      between the D, D*,f values and the estimated glomerular filtration rate (eGFR),
      serum creatinine level (SCr), 24h urinary protein level (24h-UPRO),
      histopathological fibrosis scores. RESULTS: The D, D* and f values were
      significantly lower in medulla than in the cortex for all of the participants.
      All of the IVIM parameters were significantly lower in the CKD patients than in
      the healthy controls. In the CKD patients, a significant negative correlation was
      found between the renal parenchymal D, D*,f values and the 24h-UPRO, as well as
      between the renal parenchymal D, f values and the SCr. There was a significant
      positive correlation between all of the IVIM parameters and the eGFR. All of the
      IVIM parameters exhibited a significant negative correlation with the
      histopathological fibrosis score. CONCLUSION: IVIM-DWI shows great potential in
      the noninvasive assessment of renal fibrosis in CKD.

PMID- 29217492
TI  - The potential role of IDEAL MRI for identification of lipids and hemorrhage in
      carotid artery plaques.
AB  - Hemorrhage and lipid deposits contribute to instability in atherosclerotic
      plaques. Unstable carotid artery plaques can lead to cerebral ischemic events.
      While MRI studies have shown the ability to identify plaque components, the
      identification of hemorrhage and lipids has proven to be problematic. The purpose
      of this study was to quantitatively evaluate the potential of the MRI fat/water
      separation method known as iterative decomposition of water and fat with echo
      asymmetry and least squares estimation (IDEAL) to complement and improve existing
      methods for the identification of hemorrhage and lipids in carotid artery
      plaques. Fifteen asymptomatic subjects with 50-79% stenosis of at least one
      carotid artery were enrolled. Hemorrhage and lipid components within carotid
      plaques were identified using previously published criteria based on the multiple
      contrast-weighted (MCW) method (3D Time-of-Flight (3D-TOF), T1-Weighted (T1W) and
      T2-Weighted (T2W)). The hemorrhage:muscle, lipid:muscle and intra-plaque
      lipid:hemorrhage signal intensity ratios (SIR) and contrast to noise ratios (CNR)
      were measured on MCW and compared to IDEAL black-blood images. No differences
      were found between any of the MCW methods for any of the SIRs measured. The IDEAL
      Fat images had higher lipid:muscle and lipid/hemorrhage SIRs (p<0.001) compared
      to IDEAL Water and all MCW image sequence types. The mean values of IDEAL Fat
      hemorrhage:muscle SIR and CNR were nearly unity (1.1+/-0.6) and nearly zero
      (0.1+/-1.1), respectively. The IDEAL Water imaging was not significantly
      different than any of the MCW methods for any of the SIRs or for the
      hemorrhage:muscle CNR of 3D-TOF, while its CNRs were significantly higher than
      IDEAL Fat lipid:muscle (p<0.05) and lipid:hemorrhage (p<0.001) and all MCW
      methods (p<0.001). The addition of IDEAL Water and Fat imaging to the MCW method
      shows potential to improve the identification of hemorrhage and lipid structures
      in carotid artery plaques.

PMID- 29217493
TI  - Effects of proximity and noise level of phased array coil elements on overall
      signal-to-noise in parallel MR spectroscopy.
AB  - Parallel imaging using phased array coils facilitates accelerated magnetic
      resonance imaging (MRI) and spectroscopy (MRS). Parallel data reconstruction
      requires the combination of data from individual coil elements, but limited
      combination algorithms currently exist for higher-order phased arrays and MRS
      data. Here, we present a systematic framework for identifying coil proximity
      related signal inhomogeneities and noise levels in phased array coils that may
      affect sensitivity of parallel MRS. Single-voxel MRS was acquired in nine voxel
      positions in a brain spectroscopy phantom on a 3T whole-body MR scanner using
      commercially available 64-, 32-, and 20-channel phased array coils. Spectra
      produced by individual coil elements were combined using both a signal-to-noise
      ratio (SNR) threshold and based on the position of individual coil elements. SNR
      and metabolite Cramer-Rao lower bounds (CRLBs) from the final combined spectra
      were used as metrics to compare combination strategies and the effects of the
      phased array geometry and individual coil proximity. Comparisons were performed
      using one-way repeated measures ANOVA and post-hoc Tukey's range test (p<0.05).
      The 32-channel phased array coil produced the highest overall SNR compared to the
      64-channel (p=0.0009) or 20-channel coils (p=0.003). Low SNR spectra from
      individual coil elements in the 64-channel coil can reduce the overall SNR when
      simply combining spectra from all elements. SNR varied significantly as a
      function of voxel position (F=58.3, p<0.0001) and SNR threshold for all phased
      arrays (p<0.05 for 64-, 32-, and 20-channel coils). Metabolite CRLBs were
      dependent on the combination strategy. We demonstrate the importance of the
      sampling voxel position and coil proximity on overall SNR in parallel MRS data
      acquisition, with significant SNR improvements after selectively filtering
      individual spectra based on pre-determined SNR thresholds which must be optimized
      for each phased array coil element and volume of interest.

PMID- 29217494
TI  - Regulation of the kynurenine metabolism pathway by Xiaoyao San and the underlying
      effect in the hippocampus of the depressed rat.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyao San (XYS) is a classic Chinese herbal
      formula for treatment of depression. The present study aimed to investigate the
      antidepressant effects of XYS in a rat model of chronic unpredictable mild stress
      (CUMS) and the underlying mechanisms. MATERIALS AND METHODS: A CUMS rat model of
      depression was established via 4 weeks of unpredictable stimulation. Then the
      rats were orally administered paroxetine and XYS for 2 weeks with continued
      stress. Behavioral assessments, including an open field test (OFT), sucrose
      preference test (SPT) and forced swim test (FST), were conducted to evaluate the
      antidepressant effects of XYS. The concentrations in rat plasma of tryptophan
      (Trp) and its metabolic products, including kynurenine (Kyn) and quinolinic acid
      (QUIN), were determined using high performance liquid chromatography tandem mass
      spectrometry with electrochemical detection (HPLC-MS/MS). The mRNA and protein
      levels in rat hippocampus of depression-related brain derived neurotrophic factor
      (BDNF), cyclic AMP response element binding protein (CREB) and nerve cell
      adhesion molecule (NCAM) were determined by real-time qPCR and Western blot,
      respectively. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the
      activities of indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase
      (KMO) in rat plasma. RESULTS: The results showed that a successful CUMS rat model
      was established through 4 weeks of continuous unpredictable stimulation, as
      indicated by the significant decrease in locomotor activity and increase in
      immobility time in the OFT, reduction in body weight and food intake etc.
      Compared with the normal group, the concentrations of Kyn and QUIN had
      significantly (p < 0.05) decreased at day 28 in the control group, but then
      improved after drug treatment with paroxetine and XYS. There were no obvious
      changes in the activities of IDO and KMO. Compared with the normal group, the
      mRNA of NCAM, CREB and BDNF were significantly down-regulated (p < 0.001) in the
      control group, BDNF gene was up-regulated by paroxetine or XYS treatment, NCAM
      and CREB gene did not change in XYS group, protein expressions of BDNF and CREB
      were significantly increased, and NCAM was significantly reduced (p < 0.05).
      CONCLUSIONS: XYS reversed the abnormalities of the tryptophan-kynurenine
      metabolic pathways in depressed rats and achieved an excellent antidepressant
      effect. Its direct impact may be observed as changes in biological indicators in
      rat hippocampus tissue.

PMID- 29217495
TI  - Efficacy of Violet oil, a traditional Iranian formula, in patients with chronic
      insomnia: A randomized, double-blind, placebo-controlled study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Violet oil is an ancient herbal drug which has
      been extensively used to treat insomnia in traditional Iranian Medicine clinics.
      Violet oil is an almond or sesame oil-based extract of Viola odorata, which is
      administered as nasal drops. This study aimed to evaluate the efficacy of Violet
      oil in the treatment of insomnia. METHODS AND MATERIALS: This study was conducted
      as a 3-arm double-blind randomized trial. A total of 75 patients with chronic
      insomnia were enrolled and randomly assigned to three groups in Traditional
      Iranian Medicine Clinic of Mashhad University of Medical Sciences, Mashhad, Iran.
      The treatment consisted of intranasal dropping of Violet oil, Almond oil or
      placebo (1% solution of Carboxymethyl cellulose) in each nostril every night
      before sleep for 30 days, i.e. three drops of the drug (including either Violet
      oil or Almond oil) or the placebo was used every night before the sleep. All the
      patients were asked to complete Pittsburgh Sleep Quality Index (PSQI) and
      Insomnia Severity Index (ISI) questionnaires before and after the intervention.
      RESULTS: There were no significant differences between patients in the three
      groups before the intervention (P > 0.05). However, there were significant
      differences between the three groups after the intervention in ISI scores
      (P<0.002) and PSQI scores (p<0.001). When comparing the pre- and post-treatment
      data, the ISI and PSQI scores improved significantly in all the three groups as
      follows: Violet oil (P<0.001), Almond oil (P<0.001) and placebo (P<0.001). The
      results also showed that the Violet oil had the most effect among the three
      groups. In addition, it was more effective on sleep quality than sleep quantity.
      CONCLUSION: Considering the effects of natural nasal drug on the improvement of
      sleep quality in insomniac patients, this study has proposed the use of Violet
      oil as a natural and herbal drug in a non-oral method without serious side
      effects for treatment of insomnia.

PMID- 29217496
TI  - Protective action of Crateva nurvala Buch. Ham extracts against renal ischaemia
      reperfusion injury in rats via antioxidant and anti-inflammatory activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Crateva nurvala stem bark is commonly used in
      Ayruveda in treatment of many renal injuries, e.g., urinary lithiasis, diuretic
      and nephroprotective. However, its protective effect against renal
      ischaemia/reperfusion, the major cause of acute kidney injury, has never been
      studied. Moreover, no comprehensive chemical profiling of its extracts was
      recorded. AIM OF THE STUDY: Assessment of the protective effect of the plant
      extracts against renal ischaemia/reperfusion and elucidation of the possible
      mechanism of action. Then, to determine its bioactive constituents using modern
      UPLC-HRMS technique. MATERIAL AND METHODS: Unilateral ischaemia was induced by
      clamping the left renal artery for 1h then reperfusion for 24h. Rats were divided
      in 4 groups: i) sham-operated group, ii) ischaemia/reperfusion, I/R group, iii)
      I/R protected by previous administration of Crateva leaves extract, CLE group and
      iv) I/R protected by previous administration of Crateva bark extract, CBE group.
      At the end of reperfusion, blood samples were analyzed for renal function
      biomarkers. Kidneys were examined histopathologically and their homogenates were
      used in determining the intracellular levels of oxidative stress, inflammatory,
      and apoptosis markers. RESULTS: Leaves and bark extracts attenuated the
      deleterious effects of I/R apparent in reducing LDH, creatinine and blood urea
      nitrogen levels. The extracts reduced the oxidative stress by replenishing the
      glutathione levels and Nrf2 factor levels. Moreover, extracts decreased levels of
      pro-inflammatory TNF-alpha, NF-kappabeta and IL-6; which ultimately resulted in
      reducing the pro-apoptotic caspase-3. Bark and leave extracts have quite similar
      chemical profile where 42 compounds of various chemical classes were identified.
      Flavonoids are the major class of the bioactive phytochemicals CONCLUSION: C.
      nurvala extracts had effectively ameliorated the deleterious effects of renal I/R
      by mainly counteracting oxidative stress and presumably inflammation.
      Consequently, it can be used as a complementary treatment with other agents. In
      this aspect, leaves stand as a sustainable alternative to bark. The presented
      chemical profiling can be used in future standardization and quality control of
      the drug.

PMID- 29217497
TI  - Prevalence of hyperdense paraspinal vein sign in patients with spontaneous
      intracranial hypotension without dural CSF leak on standard CT myelography.
AB  - PURPOSE: A recently identified and treatable cause of spontaneous intracranial
      hypotension (SIH) is cerebrospinal fluid (CSF)-venous fistula, and a recently
      described computed tomography myelogram (CTM) finding highly compatible with but
      not diagnostic of this entity is the hyperdense paraspinal vein sign. We aimed to
      retrospectively measure the prevalence of the hyperdense paraspinal vein sign on
      CTMs in SIH patients without dural CSF leak, in comparison with control groups.
      METHODS: Three CTM groups were identified: 1) SIH study group, which included
      dural CSF leak-negative standard CTMs performed for SIH, with early and delayed
      imaging; 2) Early control CTMs, which were performed for indications other than
      SIH, with imaging shortly after intrathecal contrast administration; 3) Delayed
      control CTMs, which included delayed imaging. CTMs were retrospectively reviewed
      for the hyperdense paraspinal vein sign by experienced neuroradiologists, blinded
      to the group assignment. All CTMs deemed by a single reader to be positive for
      the hyperdense paraspinal vein sign were independently reviewed by two additional
      neuroradiologists; findings were considered positive only if consensus was
      present among all three readers. For positive cases, noncontrast CTs and prior
      CTMs, if available, were reviewed for the presence of the sign. RESULTS: Seven of
      101 (7%) SIH patients had contrast in a spinal/paraspinal vein consistent with
      the hyperdense paraspinal vein sign; no patient in either control group (total
      n=54) demonstrated the hyperdense paraspinal vein sign (P = 0.0463). The finding
      occurred only at thoracic levels. Each patient had a single level of involvement.
      Six (86%) occurred on the right. Four occurred in female patients (57%). The sign
      was seen on early images in 3 of 7 cases (43%) and on both early and delayed
      images in 4 of 7 cases (57%). In 2 of 7 patients (29%), a noncontrast CT covering
      the relevant location was available and negative for the sign. A prior CTM was
      available in 2 of 7 patients (29%), and in both cases the hyperdense paraspinal
      vein sign was also evident. CONCLUSION: The prevalence of the hyperdense
      paraspinal vein sign in SIH patients with dural CSF leak-negative standard CTM
      was 7%. As the sign was not seen in control groups, this sign is highly
      compatible with the presence of CSF-venous fistula. Since the CTMs were not
      specifically dedicated to identifying hyperdense paraspinal veins (i.e., they
      were not dynamic and were not preceded by digital subtraction myelography), the
      true prevalence of the sign may be higher. Radiologists should scrutinize
      conventional CTMs for this sign, especially in patients in whom a traditional
      dural CSF leak is not identified.

PMID- 29217498
TI  - Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia
AB  - Sirolimus has been reported to be effective in the treatment of the diffuse form
      of congenital hyperinsulinism (CHI), unresponsive to diazoxide and octreotide,
      without causing severe side effects. Two newborns with CHI due to homozygous
      ABCC8 gene mutations were started on sirolimus aged 21 and 17 days, due to lack
      of response to medical treatment. A good response to sirolimus was observed. At
      follow-up after ten and two months of treatment, liver enzymes were found to be
      increased [serum sirolimus level 1.4 ng/mL (normal range: 5-15), aspartate
      aminotransferase (AST): 298U/L, alanine aminotransferase (ALT): 302U/L and serum
      sirolimus level: 9.9 ng/mL, AST: 261U/L, ALT: 275U/L, respectively]. In Case 1,
      discontinuation of the drug resulted in normalization of liver enzymes within
      three days. Two days after normalization, sirolimus was restarted at a lower
      dose, which resulted in a repeated increase in transferases. In Case 2, a
      reduction of sirolimus dose caused normalization of liver enzymes within ten
      days. When the dose was increased, enzymes increased within three days. Sirolimus
      was discontinued in both cases.The rapid normalization of liver enzyme levels
      after sirolimus withdrawal or dose reduction; elevation of transaminases after
      restart or dose increase and rapid normalization after sirolimus withdrawal were
      findings strongly suggestive of sirolimus-induced hepatitis.To the best of our
      knowledge, this is the first report of sirolimus-induced hepatitis in CHI.
      Sirolimus is a promising drug for CHI patients who are unresponsive to medical
      treatment, but physicians should be vigilant for adverse effects on liver
      function.

PMID- 29217499
TI  - Severe Early Onset Obesity due to a Novel Missense Mutation in Exon 3 of the
      Leptin Gene in an Infant from Northwest India
AB  - Monogenic obesity, caused by mutations in one of the genes involved in the
      control of hunger and satiety, is a rare cause of early onset obesity (EOO). The
      most common of the single gene alterations affect the leptin gene (LEP),
      resulting in congenital leptin deficiency that manifests as intense hyperphagia,
      EOO and severe obesity associated with hormonal and metabolic alterations. Only
      eight mutations of (LEP associated with congenital leptin deficiency have been
      described in humans to date. In this study, we report a novel, homozygous,
      missense mutation in exon 3 of the (LEP gene (chr7:127894610;c.298G>A) resulting
      in the amino acid substitution of asparagine for aspartic acid at codon 100
      (p.Asp100Asn) in a 10-month-old infant who presented to us with severe
      hyperphagia and EOO. She was subsequently found to have low serum leptin
      concentrations. Additionally, a homozygous missense variation of unknown
      significance in exon 11 of Bardet-Biedl syndrome-1 gene (chr11:66291279; G>A;
      Depth 168x) was detected. Significant abnormalities of lipid parameters were also
      present in our patient. Both parents were thin but there was a family history
      suggestive of EOO in a paternal uncle and a cousin. In conclusion, we report the
      second patient from India with a novel mutation of the (LEP gene associated with
      severe obesity.

PMID- 29217500
TI  - Peripheral Neuropathy as a Complication of Diabetic Ketoacidosis in a Child with
      Newly Diagnosed Diabetes Type 1: A Case Report
AB  - Neurological complications of diabetic ketoacidosis are considered to be a
      serious clinical problem. The most common complication is cerebral edema.
      However, these neurological complications also include less common entities such
      as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or
      peripheral neuropathy.We present a case of a 9-year old girl admitted to our
      intensive care unit with new onset type 1 diabetes, diabetic ketoacidosis,
      cerebral edema, multifocal vasogenic brain lesions and bilateral lower limb
      peripheral paresis. The patient developed polydipsia and polyuria one week before
      admission. The initial blood glucose level was 1136 mg/dL and severe acidosis was
      present (pH 7.1; BE-25.9). Computed tomography scan showed brain edema and a
      hypodense lesion in the left temporal region. Brain magnetic resonance imaging
      revealed more advanced multifocal brain lesions. Nerve conduction studies
      demonstrated damage of the motor neurons in both lower limbs with dysfunction in
      both peroneal nerves and the right tibial nerve. With treatment and
      physiotherapy, the patient's health gradually improved.Acute neuropathy after
      ketoacidosis is a rare complication and its pathogenesis is not clear. Patients
      with diabetic ketoacidosis require careful monitoring of neurological function,
      even after normalization of their glycemic parameters.

PMID- 29217501
TI  - A Peer-Led Electronic Mental Health Recovery App in an Adult Mental Health
      Service: Study Protocol for a Pilot Trial.
AB  - BACKGROUND: There is growing demand for peer workers (people who use their own
      lived experience to support others in their recovery) to work alongside consumers
      to improve outcomes and recovery. Augmenting the workforce with peer workers has
      strong capacity to enhance mental health and recovery outcomes and make a
      positive contribution to the workforce within mental health systems and to the
      peer workers themselves. Technology-based applications are highly engaging and
      desirable methods of service delivery. OBJECTIVE: This project is an exploratory
      proof-of-concept study, which aims to determine if a peer worker-led electronic
      mental (e-mental) health recovery program is a feasible, acceptable, and
      effective adjunct to usual treatment for people with moderate to severe mental
      illness. METHODS: The study design comprises a recovery app intervention
      delivered by a peer worker to individual consumers at an adult mental health
      service. Evaluation measures will be conducted at post-intervention. To further
      inform the acceptability and feasibility of the model, consumers will be invited
      to participate in a focus group to discuss the program. The peer worker, peer
      supervisor, and key staff at the mental health service will also be individually
      interviewed to further evaluate the feasibility of the program within the health
      service and further inform its future development. RESULTS: The program will be
      delivered over a period of approximately 4 months, commencing June 2017.
      CONCLUSIONS: If the peer worker-led recovery app is found to be feasible,
      acceptable, and effective, it could be used to improve recovery in mental health
      service consumers.

PMID- 29217502
TI  - The Impact of a Mobile Diabetes Health Intervention on Diabetes Distress and
      Depression Among Adults: Secondary Analysis of a Cluster Randomized Controlled
      Trial.
AB  - BACKGROUND: Diabetes is a complex, demanding disease that requires the constant
      attention of patients. The burden of self-management, including different
      medication regimens, routine self-care activities, and provider visits, has an
      impact on patients' emotional well-being. Diabetes distress and depression are
      two important components of emotional well-being that may negatively affect
      diabetes outcomes. OBJECTIVE: The aim was to determine the impact of the 1-year
      Mobile Diabetes Intervention Study cluster randomized clinical trial on emotional
      well-being measured by diabetes distress and depression among adults with type 2
      diabetes (T2D). METHODS: A total of 163 adults with not-well-managed T2D were
      enrolled from community primary care practices. Primary care practices were
      cluster randomized into either a usual care control group or intervention group.
      Intervention participants were given a mobile phone with coaching software
      including a Web portal to communicate with providers. A priori established
      secondary outcomes included distress measured by the Diabetes Distress Scale
      (DDS), with subscales measuring emotional burden, interpersonal distress,
      physician-related distress, and regimen-related distress, as well as depression
      measured by the Patient Health Questionnaire (PHQ-9). Linear mixed models were
      used to calculate the effect of the intervention on diabetes distress levels over
      time, both overall and separately by sex, and to determine if the intervention
      affected distress or depression. The impact of total DDS on changes in HbA1c was
      also studied. RESULTS: There were no significant treatment group effects for DDS
      total (baseline: P=.07; differences over time: P=.38) or for depression (P=.06
      over time). Significant declines in total DDS were observed over the 12-month
      intervention period (P=.01). Regimen-related distress significantly decreased for
      all study participants (P<.001), but no significant change over time was observed
      for emotional burden (P=.83), interpersonal distress (P=.64), or physician
      related distress (P=.73). Women in both the usual care and intervention groups
      were more likely to have higher overall DDS, emotional burden, physician-related
      distress, and regimen-related distress, but not interpersonal distress. Women
      also reported higher baseline depression compared to men (P=.006). Overall,
      depression decreased over the treatment period (P=.007), but remained unaffected
      by group assignment (P=.06) or by sex (P=.97). Diabetes distress had no effect on
      the change in HbA1c (P=.91) over the treatment period. CONCLUSIONS: Although we
      found no definitive overall or sex-specific effect of the intervention on
      diabetes distress or depression, this study makes an important contribution to
      the understanding of mobile health interventions and the impact on emotional
      health. Our study verified previous work that although diabetes distress and
      depression are highly correlated, these measures are not evaluating the same
      construct. Design of future mobile technology provides an opportunity to
      personalize, contextualize, and intervene in the emotional well-being of persons
      with diabetes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01107015;
      https://clinicaltrials.gov/ct2/show/NCT01107015 (Archived by WebCite at
      http://www.webcitation.org/6vVgRCLAF).

PMID- 29217503
TI  - Impact of an Electronic Health Record-Integrated Personal Health Record on
      Patient Participation in Health Care: Development and Randomized Controlled Trial
      of MyHealthKeeper.
AB  - BACKGROUND: Personal health record (PHR)-based health care management systems can
      improve patient engagement and data-driven medical diagnosis in a clinical
      setting. OBJECTIVE: The purpose of this study was (1) to demonstrate the
      development of an electronic health record (EHR)-tethered PHR app named
      MyHealthKeeper, which can retrieve data from a wearable device and deliver these
      data to a hospital EHR system, and (2) to study the effectiveness of a PHR data
      driven clinical intervention with clinical trial results. METHODS: To improve the
      conventional EHR-tethered PHR, we ascertained clinicians' unmet needs regarding
      PHR functionality and the data frequently used in the field through a cocreation
      workshop. We incorporated the requirements into the system design and
      architecture of the MyHealthKeeper PHR module. We constructed the app and
      validated the effectiveness of the PHR module by conducting a 4-week clinical
      trial. We used a commercially available activity tracker (Misfit) to collect
      individual physical activity data, and developed the MyHealthKeeper mobile phone
      app to record participants' patterns of daily food intake and activity logs. We
      randomly assigned 80 participants to either the PHR-based intervention group
      (n=51) or the control group (n=29). All of the study participants completed a
      paper-based survey, a laboratory test, a physical examination, and an opinion
      interview. During the 4-week study period, we collected health-related mobile
      data, and study participants visited the outpatient clinic twice and received PHR
      based clinical diagnosis and recommendations. RESULTS: A total of 68 participants
      (44 in the intervention group and 24 in the control group) completed the study.
      The PHR intervention group showed significantly higher weight loss than the
      control group (mean 1.4 kg, 95% CI 0.9-1.9; P<.001) at the final week (week 4).
      In addition, triglyceride levels were significantly lower by the end of the study
      period (mean 2.59 mmol/L, 95% CI 17.6-75.8; P=.002). CONCLUSIONS: We developed an
      innovative EHR-tethered PHR system that allowed clinicians and patients to share
      lifelog data. This study shows the effectiveness of a patient-managed and
      clinician-guided health tracker system and its potential to improve patient
      clinical profiles. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200119;
      https://clinicaltrials.gov/ct2/show/NCT03200119 (Archived by WebCite at
      http://www.webcitation.org/6v01HaCdd).

PMID- 29217504
TI  - Challenges During Implementation of a Patient-Facing Mobile App for Surgical
      Rehabilitation: Feasibility Study.
AB  - BACKGROUND: Translating research into practice, especially the implementation of
      digital health technologies in routine care, is increasingly important. Yet,
      there are few studies examining the challenges of implementing patient-facing
      digital technologies in health care settings. OBJECTIVE: The aim of this study
      was to report challenges experienced when implementing mobile apps for patients
      to support their postsurgical rehabilitation in an orthopedic setting. METHODS: A
      mobile app was tailored to the needs of patients undergoing rotator cuff repair.
      A 30-min usability session and a 12-week feasibility study were conducted with
      patients to evaluate the app in routine care. Implementation records (observation
      reports, issues log, and email correspondence) explored factors that hindered or
      facilitated patient acceptance. Interviews with clinicians explored factors that
      influenced app integration in routine care. RESULTS: Participant completion was
      low (47%, 9/19). Factors that affected patient acceptance included digital
      literacy, health status, information technology (IT) infrastructure at home,
      privacy concerns, time limitations, the role of a caregiver, inconsistencies in
      instruction received from clinicians and the app, and app advice not reflective
      of patient progress over time. Factors that negatively influenced app integration
      in routine care included competing demands among clinicians, IT infrastructure in
      health care settings, identifying the right time to introduce the app to
      patients, user interface complexity for older patients, lack of coordination
      among multidisciplinary clinicians, and technical issues with app installation.
      CONCLUSIONS: Three insights were identified for mobile app implementation in
      routine care: (1) apps for patients need to reflect their journey over time and
      in particular, postoperative apps ought to be introduced as part of preoperative
      care with opportunities for patients to learn and adopt the app during their
      postoperative journey; (2) strategies to address digital literacy issues among
      patients and clinicians are essential; and (3) impact of the app on patient
      outcomes and clinician workflow needs to be communicated, monitored, and
      reviewed. Lastly, digital health interventions should supplement but not replace
      patient interaction with clinicians.

PMID- 29217506
TI  - Leading doctors back legal action to force UK government to cut carbon emissions.

PMID- 29217505
TI  - Eating disorders in children and young people.

PMID- 29217507
TI  - Multidisciplinary Approach to Understand Medial Arterial Calcification.
AB  - OBJECTIVE: Vascular calcification significantly increases morbidity in life
      threatening diseases, and no treatments are available because of lack of
      understanding of the underlying molecular mechanism. Here, we study the
      physicochemical details of mineral nucleation and growth in an animal model that
      faithfully recapitulates medial arterial calcification in humans, to understand
      how pathological calcification is initiated on the vascular extracellular matrix.
      APPROACH AND RESULTS: MGP (matrix Gla protein) is a potent mineralization
      inhibitor. We study the evolution of medial calcification in MGP-deficient mice
      over the course of 5 weeks using a combination of material science techniques and
      find that mineral composition and crystallinity evolve over time and space. We
      show that calcium is adsorbed first and then amorphous calcium phosphate and
      octacalcium phosphate forms, which then transform into hydroxyapatite and
      carbonated apatite. These events are repeated after each nucleation event,
      providing a snapshot of the overall mineral evolution at each time point
      analyzed. CONCLUSIONS: Our results show that an interdisciplinary approach
      combining animal models and materials science can provide insights into the
      mechanism of vascular calcification and suggest the importance of analyzing
      mineral phases, rather than just overall mineralization extent, to diagnose and
      possibly prevent disease development.

PMID- 29217508
TI  - IL-1beta (Interleukin-1beta) and TNF-alpha (Tumor Necrosis Factor-alpha) Impact
      Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage
      Polarization.
AB  - OBJECTIVE: Abdominal aortic aneurysms are inflammatory in nature and are
      associated with some risk factors that also lead to atherosclerotic occlusive
      disease, most notably smoking. The purpose of our study was to identify
      differential cytokine expression in patients with abdominal aortic aneurysm and
      those with atherosclerotic occlusive disease. Based on this analysis, we further
      explored and compared the mechanism of action of IL (interleukin)-1beta versus
      TNF-alpha (tumor necrosis factor-alpha) in abdominal aortic aneurysm formation.
      APPROACH AND RESULTS: IL-1beta was differentially expressed in human plasma with
      lower levels detected in patients with abdominal aortic aneurysm compared with
      matched atherosclerotic controls. We further explored its mechanism of action
      using a murine model and cell culture. Genetic deletion of IL-1beta and IL-1R did
      not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase)
      expression. The effects of IL-1beta deletion on M1 macrophage polarization were
      compared with another proinflammatory cytokine, TNF-alpha. Bone marrow-derived
      macrophages from IL-1beta-/- and TNF-alpha-/- mice were polarized to an M1
      phenotype. TNF-alpha deletion, but not IL-1beta deletion, inhibited M1 macrophage
      polarization. Infusion of M1 polarized TNF-alpha-/- macrophages inhibited aortic
      diameter growth; no inhibitory effect was seen in mice infused with M1 polarized
      IL-1beta-/- macrophages. CONCLUSIONS: Although IL-1beta is a proinflammatory
      cytokine, its effects on aneurysm formation and macrophage polarization differ
      from TNF-alpha. The differential effects of IL-1beta and TNF-alpha inhibition are
      related to M1/M2 macrophage polarization and this may account for the differences
      in clinical efficacy of IL-1beta and TNF-alpha antibody therapies in management
      of inflammatory diseases.

PMID- 29217510
TI  - Loss of Vascular Myogenic Tone in miR-143/145 Knockout Mice Is Associated With
      Hypertension-Induced Vascular Lesions in Small Mesenteric Arteries.
AB  - OBJECTIVE: Pressure-induced myogenic tone is involved in autoregulation of local
      blood flow and confers protection against excessive pressure levels in small
      arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs
      (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the
      consequences of altered myogenic tone for hypertension-induced damage to small
      arteries are not well understood. APPROACH AND RESULTS: The importance of smooth
      muscle-enriched microRNAs, miR-143/145, for myogenic tone was evaluated in miR
      143/145 knockout mice. Furthermore, hypertension-induced vascular injury was
      evaluated in mesenteric arteries in vivo after angiotensin II infusion. Myogenic
      tone was abolished in miR-143/145 knockout mesenteric arteries, whereas
      contraction in response to calyculin A and potassium chloride was reduced by
      ~30%. Furthermore, myogenic responsiveness was potentiated by angiotensin II in
      wild-type but not in knockout mice. Angiotensin II administration in vivo
      elevated systemic blood pressure in both genotypes. Hypertensive knockout mice
      developed severe vascular lesions characterized by vascular inflammation,
      adventitial fibrosis, and neointimal hyperplasia in small mesenteric arteries.
      This was associated with depolymerization of actin filaments and fragmentation of
      the elastic laminae at the sites of vascular lesions. CONCLUSIONS: This study
      demonstrates that miR-143/145 expression is essential for myogenic
      responsiveness. During hypertension, loss of myogenic tone results in potentially
      damaging levels of mechanical stress and detrimental effects on small arteries.
      The results presented herein provide novel insights into the pathogenesis of
      vascular disease and emphasize the importance of controlling mechanical factors
      to maintain structural integrity of the vascular wall.

PMID- 29217511
TI  - Make detaining patients who can't pay their medical bills illegal.

PMID- 29217509
TI  - Macrophage-Associated Lipin-1 Enzymatic Activity Contributes to Modified Low
      Density Lipoprotein-Induced Proinflammatory Signaling and Atherosclerosis.
AB  - OBJECTIVE: Macrophage proinflammatory responses induced by modified low-density
      lipoproteins (modLDL) contribute to atherosclerotic progression. How modLDL
      causes macrophages to become proinflammatory is still enigmatic. Macrophage foam
      cell formation induced by modLDL requires glycerolipid synthesis. Lipin-1, a key
      enzyme in the glycerolipid synthesis pathway, contributes to modLDL-elicited
      macrophage proinflammatory responses in vitro. The objective of this study was to
      determine whether macrophage-associated lipin-1 contributes to atherogenesis and
      to assess its role in modLDL-mediated signaling in macrophages. APPROACH AND
      RESULTS: We developed mice lacking lipin-1 in myeloid-derived cells and used
      adeno-associated viral vector 8 expressing the gain-of-function mutation of mouse
      proprotein convertase subtilisin/kexin type 9 (adeno-associated viral vector 8
      proprotein convertase subtilisin/kexin type 9) to induce hypercholesterolemia and
      plaque formation. Mice lacking myeloid-associated lipin-1 had reduced
      atherosclerotic burden compared with control mice despite similar plasma lipid
      levels. Stimulation of bone marrow-derived macrophages with modLDL activated a
      persistent protein kinase Calpha/betaII-extracellular receptor kinase1/2-jun
      proto-oncogene signaling cascade that contributed to macrophage proinflammatory
      responses that was dependent on lipin-1 enzymatic activity. CONCLUSIONS: Our data
      demonstrate that macrophage-associated lipin-1 is atherogenic, likely through
      persistent activation of a protein kinase Calpha/betaII-extracellular receptor
      kinase1/2-jun proto-oncogene signaling cascade that contributes to foam cell
      proinflammatory responses. Taken together, these results suggest that modLDL
      induced foam cell formation and modLDL-induced macrophage proinflammatory
      responses are not independent consequences of modLDL stimulation but rather are
      both directly influenced by enhanced lipid synthesis.

PMID- 29217512
TI  - Hospital gardens are making a comeback.

PMID- 29217513
TI  - Seven days in medicine: 29 November to 5 December 2017.

PMID- 29217514
TI  - Editors' note: Novel ocular toxicity associated with fibroblast growth factor
      receptor (FGFR) inhibitors in cancer treatment: observational case series.

PMID- 29217515
TI  - Choroidal neovascular membrane in paediatric patients: clinical characteristics
      and outcomes.
AB  - PURPOSE: To analyse the clinical characteristics and treatment outcomes of
      choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric
      retina referral centres. METHODS: Medical charts of patients aged 18 years or
      less with a diagnosis of CNVM were retrospectively reviewed. The demographic
      profile, laterality, presenting complaint, corrected vision, underlying
      pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram
      (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and
      final visual acuity were noted. RESULTS: There were a total of 35 subjects (43
      eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%),
      classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular
      dystrophy was found to be the most common association (32.5%). Intravitreal
      injection of an anti-vascular endothelial growth factor (VEGF) agent was the
      initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone
      required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had
      an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with
      repeat anti-VEGF treatment, the remaining patients required photodynamic therapy,
      laser or surgery. CONCLUSION: Paediatric CNVMs in this series differed from those
      in the adult population with regard to aetiology, OCT and angiographic
      characteristics, treatment response and rate of recurrence.

PMID- 29217516
TI  - Care planning meetings can aid communication with patient and family.

PMID- 29217517
TI  - Assessment of child or young person with a possible eating disorder.

PMID- 29217518
TI  - Enhancement of mammary tumour growth by IGFBP-3 involves impaired T cell
      accumulation.
AB  - Epidemiological studies show an association between obesity and poor breast
      cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in
      IGFBP-3-null mice, resulted in a 50% reduction in mammary tumour growth over 3
      weeks relative to tumours in wild-type (WT) C57BL/6 mice. This growth reduction
      was ameliorated by high fat feeding-induced obesity. This study aimed to examine
      how IGFBP-3 promotes tumour growth by influencing the immune tumour
      microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack
      detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3
      null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and
      examined by quantitative PCR and immunohistochemistry. In WT mice, increased
      stromal expression of IGFBP-3 was positively associated with tumour growth,
      supporting the hypothesis that IGFBP-3 in the microenvironment promotes tumour
      progression. Examining markers of immune cell subsets, gene expression of Ifng,
      Cd8a, Cd8b1 and Tnf and CD8 measured by immunohistochemistry were elevated in
      tumours of IGFBP-3-null mice compared to WT, indicating an accumulation of CD8+ T
      cells, but this increase was absent if the IGFBP-3-null mice had been exposed to
      HFD. Expression of these genes was negatively associated with tumour growth.
      Although similar among groups overall, Nkg2d and Tnfsf10 tumoural expression was
      associated with decreased tumour growth. Overall, the results of this study
      provide an immune-based mechanism by which host IGFBP-3 may promote breast tumour
      growth in the EO771 murine breast cancer model, and suggest that targeting IGFBP
      3 might make a novel contribution to immune therapy for breast cancer.

PMID- 29217519
TI  - Conscientious objection in sexual and reproductive health - a guideline that
      respects diverse views but emphasises patients' rights.

PMID- 29217520
TI  - Alex Azar: critics cry "revolving door" as Trump picks pharma executive for top
      US health job.

PMID- 29217521
TI  - Laser Balloon or Wide-Area Circumferential Irrigated Radiofrequency Ablation for
      Persistent Atrial Fibrillation: A Multicenter Prospective Randomized Study.
AB  - BACKGROUND: Pulmonary vein isolation is the cornerstone of ablation for
      persistent atrial fibrillation (AF). The role of balloon catheters in this
      patient population remains ill defined. We sought to compare efficacy and safety
      of the laser balloon (LB) with wide-area circumferential pulmonary vein isolation
      using irrigated radiofrequency current (RF) ablation and 3-dimensional mapping.
      METHODS AND RESULTS: In 6 European centers, patients with persistent AF were
      prospectively randomized. Follow-up included 3-day Holter ECG recordings and
      office visits at 3, 6, and 12 months. The primary efficacy end point was freedom
      from AF between 90 and 365 days after a single ablation. The primary safety end
      point was the incidence of any periprocedural complications. Of 152 enrolled
      patients, 134 (n=68 LB and 66 RF; 63% men; mean age, 66+10 years) with persistent
      AF (median AF history, 14 months; Q1-Q3, 7-36 months) underwent pulmonary vein
      isolation and completed the entire follow-up. Baseline parameters were similar in
      both groups. Procedure and fluoroscopy times were similar in both groups (135+/
      38 and 14+/-9 minutes (LB) versus 128+/-51 and 11+/-9 minutes). The primary
      efficacy end point was met by 71.2% versus 69.3%, in the LB and RF groups,
      respectively (P=0.40). In the LB group, stroke (n=1), a false aneurysm (n=1), and
      phrenic nerve palsy (n=1) were observed. In the RF group, 2 patients developed a
      false aneurysm, and 1 patient needed surgical repair. CONCLUSIONS: An LB-guided
      strategy was associated with similar efficacy as wide-area circumferential
      pulmonary vein isolation using irrigated RF in patients with persistent AF.
      CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.org. Unique identifier:
      NCT01863472.

PMID- 29217522
TI  - Drosophila Syd-1 Has RhoGAP Activity That Is Required for Presynaptic Clustering
      of Bruchpilot/ELKS but Not Neurexin-1.
AB  - Syd-1 proteins are required for presynaptic development in worm, fly, and mouse.
      Syd-1 proteins in all three species contain a Rho GTPase activating protein (GAP)
      like domain of unclear significance: invertebrate Syd-1s are thought to lack GAP
      activity, and mouse mSYD1A has GAP activity that is thought to be dispensable for
      its function. Here, we show that Drosophila melanogaster Syd-1 can interact with
      all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development,
      fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction
      (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone
      (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly. We show that
      a mutant form of Syd-1 that specifically lacks GAP activity localizes normally to
      presynaptic sites and is sufficient to recruit Nrx-1 but fails to cluster Brp
      normally. We provide evidence that Syd-1 participates with Rac1 in two separate
      functions: (1) together with the Rac guanine exchange factor (RacGEF) Trio, GAP
      active Syd-1 is required to regulate the nucleotide-bound state of Rac1, thereby
      promoting Brp clustering; and (2) Syd-1, independent of its GAP activity, is
      required for the recruitment of Nrx-1 to boutons, including the recruitment of
      Nrx-1 that is promoted by GTP-bound Rac1. We conclude that, contrary to current
      models, the GAP domain of fly Syd-1 is active and required for presynaptic
      development; we suggest that the same may be true of vertebrate Syd-1 proteins.
      In addition, our data provide new molecular insight into the ability of Rac1 to
      promote presynaptic development.

PMID- 29217525
TI  - Integration of Mobile Devices to Facilitate Patient Care and Teaching During
      Family-Centered Rounds.
AB  - OBJECTIVES: The increasing prevalence of mobile devices in clinical settings has
      the potential to improve both patient care and education. The benefits are
      particularly promising in the context of family-centered rounds in inpatient
      pediatric settings. We aimed to increase mobile device usage by inpatient
      rounding teams by 50% in 6 months. We hoped to demonstrate that use of mobile
      devices would improve access to patient care and educational information and to
      determine if use would improve efficiency and perceptions of clinical teaching.
      METHODS: We designed a mixed-methods study involving pre- and post-implementation
      surveys to residents, families, and faculty as well as direct observations of
      family-centered rounds. We conducted rapid cycles of continual quality
      improvement by using the Plan-Do-Study-Act framework involving 3 interventions.
      RESULTS: Pre-intervention, the mobile computing cart was used for resident
      education on average 3.3 times per rounding session. After cycle 3, teaching
      through the use of mobile devices increased by ~79% to 5.9 times per rounding
      session. On the basis of survey data, we determined there was a statistically
      significant increase in residents' perception of feeling prepared for rounds,
      receiving teaching on clinical care, and ability to teach families. Additionally,
      average time spent per patient on rounds decreased after implementation of mobile
      devices. CONCLUSIONS: Integration of mobile devices into a pediatric hospital
      medicine teaching service can facilitate patient care and perception of resident
      teaching by extending the utility of electronic medical records in care decisions
      and by improving access to knowledge resources.

PMID- 29217523
TI  - Detecting Recent Positive Selection with a Single Locus Test Bipartitioning the
      Coalescent Tree.
AB  - Many population genomic studies have been conducted in the past to search for
      traces of recent events of positive selection. These traces, however, can be
      obscured by temporal variation of population size or other demographic factors.
      To reduce the confounding impact of demography, the coalescent tree topology has
      been used as an additional source of information for detecting recent positive
      selection in a population or a species. Based on the branching pattern at the
      root, we partition the hypothetical coalescent tree, inferred from a sequence
      sample, into two subtrees. The reasoning is that positive selection could impose
      a strong impact on branch length in one of the two subtrees while demography has
      the same effect on average on both subtrees. Thus, positive selection should be
      detectable by comparing statistics calculated for the two subtrees. Simulations
      demonstrate that the proposed test based on these principles has high power to
      detect recent positive selection even when DNA polymorphism data from only one
      locus is available, and that it is robust to the confounding effect of
      demography. One feature is that all components in the summary statistics
      ([Formula: see text]) can be computed analytically. Moreover, misinference of
      derived and ancestral alleles is seen to have only a limited effect on the test,
      and it therefore avoids a notorious problem when searching for traces of recent
      positive selection.

PMID- 29217524
TI  - MiR-29a: a potential therapeutic target and promising biomarker in tumors.
AB  - MiRNAs, small non-coding RNA molecules, were recognized to be associated with the
      incidence and development of diverse neoplasms. MiRNAs were small non-coding RNAs
      that could regulate post-transcriptional level by binding to 3'-UTR of target
      mRNAs. Amongst which, miR-29a was demonstrated that it had significant impact on
      oncogenicity in various neoplasms through binding to critical genes which
      enhanced or inhibited the progression of cancers. MiR-29a participated in kinds
      of physiological and pathological processes, including virus replication, cell
      proliferation, differentiation, apoptosis, fibrosis, angiogenesis,
      tumorigenicity, metastasis, drug-resistance, and so on. According to its
      sufficient sensitivity and specificity, many studies showed that miR-29a might
      serve as a potential therapeutic target and promising biomarker in various
      tumors. In this review, we discussed the functions of miR-29a and its potential
      application in the diagnosis, treatment and stages of carcinoma, which could
      provide additional insight to develop a novel therapeutic strategy.

PMID- 29217526
TI  - First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class
      Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with
      Advanced Solid Tumors.
AB  - Purpose: Vanucizumab is an investigational antiangiogenic, first-in-class,
      bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human
      study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor
      activity of vanucizumab in adults with advanced solid tumors refractory to
      standard therapies.Experimental Design: Patients received escalating biweekly (3
      30 mg/kg) or weekly (10-30 mg/kg) intravenous doses guided by a Bayesian logistic
      regression model with overdose control.Results: Forty-two patients were treated.
      One dose-limiting toxicity, a fatal pulmonary hemorrhage from a large centrally
      located mediastinal mass judged possibly related to vanucizumab, occurred with
      the 19 mg/kg biweekly dose. Arterial hypertension (59.5%), asthenia (42.9%), and
      headache (31%) were the most common toxicities. Seventeen (41%) patients
      experienced treatment-related grade >=3 toxicities. Toxicity was generally higher
      with weekly than biweekly dosing. A MTD of vanucizumab was not reached in either
      schedule. Pharmacokinetics were dose-linear with an elimination half-life of 6-9
      days. All patients had reduced plasma levels of free VEGF-A and Ang-2; most had
      reductions in KTRANS (measured by dynamic contrast-enhanced MRI). Two patients
      (renal cell and colon cancer) treated with 30 mg/kg achieved confirmed partial
      responses. Ten patients were without disease progression for >=6 months. A flat
      fixed 2,000 mg biweekly dose (phamacokinetically equivalent to 30 mg/kg biweekly)
      was recommended for further investigation.Conclusions: Biweekly vanucizumab had
      an acceptable safety and tolerability profile consistent with single-agent use of
      selective inhibitors of the VEGF-A and Ang/Tie2 pathway. Vanucizumab modulated
      its angiogenic targets, impacted tumor vascularity, and demonstrated encouraging
      antitumor activity in this heterogeneous population. Clin Cancer Res; 24(7); 1536
      45. (c)2017 AACR.

PMID- 29217527
TI  - Merkel Cell Carcinoma in the Age of Immunotherapy: Facts and Hopes.
AB  - Merkel cell carcinoma (MCC) is a rare (~2,000 U.S. cases/year) but aggressive
      neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only
      infrequently (<10% of cases) offers durable clinical responses (>1 year),
      suggesting a great need for improved therapeutic options. In 2008, the Merkel
      cell polyomavirus (MCPyV) was discovered and is clonally integrated in
      approximately 80% of MCC tumors. The remaining 20% of MCC tumors have large
      numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens
      in virus-negative tumors and the MCPyV T antigen oncogenes that are required for
      virus-positive tumor growth are immunogenic. Indeed, antigen-specific T cells
      detected in patients are frequently dysfunctional/"exhausted," and the inhibitory
      ligand, PD-L1, is often present in MCC tumors. These findings led to recent
      clinical trials involving PD-1 pathway blockade in advanced MCC. The combined
      data from these trials involving three PD-1 pathway blocking agents-avelumab,
      pembrolizumab, and nivolumab-indicated a high frequency of durable responses in
      treated patients. Of note, prior treatment with chemotherapy was associated with
      decreased response rates to PD-1 checkpoint blockade. Over the past year, these
      striking data led to major changes in advanced MCC therapy, including the first
      ever FDA drug approval for this disease. Despite these successes, approximately
      50% of patients with MCC do not persistently benefit from PD-1 pathway blockade,
      underscoring the need for novel strategies to broaden antitumor immune responses
      in these patients. Here, we highlight recent progress in MCC including the
      underlying mechanisms of immune evasion and emerging approaches to augment the
      efficacy of PD-1 pathway blockade. Clin Cancer Res; 24(9); 2035-43. (c)2017 AACR.

PMID- 29217529
TI  - FAM198B Is Associated with Prolonged Survival and Inhibits Metastasis in Lung
      Adenocarcinoma via Blockage of ERK-Mediated MMP-1 Expression.
AB  - Purpose: The comprehensive understanding of mechanisms involved in the tumor
      metastasis is urgently needed for discovering novel metastasis-related genes for
      developing effective diagnoses and treatments for lung cancer.Experimental
      Design: FAM198B was identified from an isogenic lung cancer metastasis cell model
      by microarray analysis. To investigate the clinical relevance of FAM198B, the
      FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by
      quantitative real-time PCR and correlated to patients' survivals. The impact of
      FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro
      cellular assays and in vivo mouse models. In addition, the N-glycosylation
      defective FAM198B mutants generated by site-directed mutagenesis were used to
      study protein stability and subcellular localization of FAM198B. Finally, the
      microarray and pathway analyses were used to elucidate the underlying mechanisms
      of FAM198B-mediated tumor suppression.Results: We found that the high expression
      of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma
      patients and in a lung cancer public database. Enforced expression of FAM198B
      inhibited cell invasion, migration, mobility, proliferation, and anchorage
      independent growth, and FAM198B silencing exhibited opposite activities in vitro
      FAM198B also attenuated tumor growth and metastasis in vivo We further identified
      MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1
      downregulation was via inhibition of the phosphorylation of ERK. Interestingly
      deglycosylation nearly eliminated the metastasis suppression activity of FAM198B
      due to a decrease of protein stability.Conclusions: Our results implicate FAM198B
      as a potential tumor suppressor and to be a prognostic marker in lung
      adenocarcinoma. Clin Cancer Res; 24(4); 916-26. (c)2017 AACR.

PMID- 29217528
TI  - T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma
      Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling.
AB  - Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered
      dysfunctional, yet the optimal target for immune checkpoint blockade is unknown.
      Characterizing coinhibitory receptor expression patterns and signaling responses
      in FL T-cell subsets might reveal new therapeutic targets.Experimental Design:
      Surface expression of 9 coinhibitory receptors governing T-cell function was
      characterized in T-cell subsets from FL lymph node tumors and from healthy donor
      tonsils and peripheral blood samples, using high-dimensional flow cytometry. The
      results were integrated with T-cell receptor (TCR)-induced signaling and cytokine
      production. Expression of T-cell immunoglobulin and ITIM domain (TIGIT) ligands
      was detected by immunohistochemistry.Results: TIGIT was a frequently expressed
      coinhibitory receptor in FL, expressed by the majority of CD8 T effector memory
      cells, which commonly coexpressed exhaustion markers such as PD-1 and CD244. CD8
      FL T cells demonstrated highly reduced TCR-induced phosphorylation (p) of ERK and
      reduced production of IFNgamma, while TCR proximal signaling (p-CD3zeta, p-SLP76)
      was not affected. The TIGIT ligands CD112 and CD155 were expressed by follicular
      dendritic cells in the tumor microenvironment. Dysfunctional TCR signaling
      correlated with TIGIT expression in FL CD8 T cells and could be fully restored
      upon in vitro culture. The costimulatory receptor CD226 was downregulated in
      TIGIT+ compared with TIGIT- CD8 FL T cells, further skewing the balance toward
      immunosuppression.Conclusions: TIGIT blockade is a relevant strategy for improved
      immunotherapy in FL. A deeper understanding of the interplay between coinhibitory
      receptors and key T-cell signaling events can further assist in engineering
      immunotherapeutic regimens to improve clinical outcomes of cancer patients. Clin
      Cancer Res; 24(4); 870-81. (c)2017 AACR.

PMID- 29217531
TI  - Proposal to disregard athletics world records prior to 2005: a radical and
      misjudged initiative.

PMID- 29217530
TI  - The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with
      Targetable Mutations-The Lung Cancer Mutation Consortium (LCMC2).
AB  - Purpose: Multiplex genomic profiling is standard of care for patients with
      advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a
      multi-institutional effort to identify and treat oncogenic driver events in
      patients with lung adenocarcinomas.Experimental Design: Sixteen U.S. institutions
      enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and
      had at least one of 14 cancer-related genes profiled using validated methods
      including genotyping, massively parallel sequencing, and IHC.Results: The use of
      targeted therapies in patients with EGFR, ERBB2, or BRAF p.V600E mutations, ALK,
      ROS1, or RET rearrangements, or MET amplification was associated with a survival
      increment of 1.5 years compared with those with such mutations not receiving
      targeted therapy, and 1.0 year compared with those lacking a targetable driver.
      Importantly, 60 patients with a history of smoking derived similar survival
      benefit from targeted therapy for alterations in EGFR/ALK/ROS1, when compared
      with 75 never smokers with the same alterations. In addition, coexisting TP53
      mutations were associated with shorter survival among patients with EGFR, ALK, or
      ROS1 alterations.Conclusion: Patients with adenocarcinoma of the lung and an
      oncogenic driver mutation treated with effective targeted therapy have a longer
      survival, regardless of prior smoking history. Molecular testing should be
      performed on all individuals with lung adenocarcinomas irrespective of clinical
      characteristics. Routine use of massively parallel sequencing enables detection
      of both targetable driver alterations and tumor suppressor gene and other
      alterations that have potential significance for therapy selection and as
      predictive markers for the efficacy of treatment. Clin Cancer Res; 24(5); 1038
      47. (c)2017 AACR.

PMID- 29217532
TI  - Imaging-detected acute muscle injuries in athletes participating in the Rio de
      Janeiro 2016 Summer Olympic Games.
AB  - BACKGROUND: Acute muscle injuries in elite athletes are responsible for a large
      portion of time loss injuries. AIM: To describe the frequency, the anatomic
      distribution, and severity of imaging-detected acute muscle injuries among
      athletes who competed in the Rio de Janeiro 2016 Summer Olympics. METHODS: We
      recorded all sports injuries reported by the National Olympic Committee medical
      teams and the Organising Committee medical staff during the 2016 Summer Olympics.
      Imaging of acute muscle injuries was performed at the IOC's polyclinic within the
      Olympic Village using ultrasound and 3.0 T and 1.5 T MRI scanners. The assessment
      of images was performed centrally by three musculoskeletal radiologists. The
      distribution of injuries by anatomic location and sports discipline and the
      severity of injuries were recorded. RESULTS: In total, 11 274 athletes from 207
      teams were included. A total of 1101 injuries were reported. Central review of
      radiological images revealed 81 acute muscle injuries in 77 athletes (66% male,
      mean age: 25.4 years, range 18-38 years). Athletics (track and field) athletes
      were the most commonly affected (n=39, 48%), followed by football players (n=9,
      11%). The majority of injuries affected muscles from lower limbs (n=68, 84%),
      with the hamstring being the most commonly involved. Most injuries were grade 2
      injuries according to the Peetrons classification (n=44, 54%), and we found 18
      injuries exhibiting intramuscular tendon involvement on MRI. CONCLUSION: Imaging
      detected acute muscle injuries during the 2016 Summer Olympics affected mainly
      thigh muscles in athletics disciplines.

PMID- 29217533
TI  - Rigorous qualitative research in sports, exercise and musculoskeletal medicine
      journals is important and relevant.

PMID- 29217534
TI  - Getting the systematic review basics right helps clinical practice: 4 common
      pitfalls for systematic review authors to avoid.

PMID- 29217536
TI  - Correction to "Metabolic Disposition of Luteolin Is Mediated by the Interplay of
      UDP-Glucuronosyltransferases and Catechol-O-Methyltransferases in Rats".

PMID- 29217535
TI  - In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to
      hematopoietic fate.
AB  - Cell fate is established through coordinated gene expression programs in
      individual cells. Regulatory networks that include the Gata2 transcription factor
      play central roles in hematopoietic fate establishment. Although Gata2 is
      essential to the embryonic development and function of hematopoietic stem cells
      that form the adult hierarchy, little is known about the in vivo expression
      dynamics of Gata2 in single cells. Here, we examine Gata2 expression in single
      aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos.
      Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter
      expression in cells undergoing endothelial-to-hematopoietic transition. Moreover,
      Gata2 reporter pulsatile expression is dramatically altered in Gata2+/- aortic
      cells, which undergo fewer transitions and are reduced in hematopoietic
      potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a
      highly unstable genetic state in single cells concomitant with their transition
      to hematopoietic fate. This reinforces the notion that threshold levels of Gata2
      influence fate establishment and has implications for transcription factor
      related hematologic dysfunctions.

PMID- 29217537
TI  - Characteristics and Performance of Unilateral Kidney Transplants from Deceased
      Donors.
AB  - BACKGROUND AND OBJECTIVES: The fraction of kidneys procured for transplant that
      are discarded is rising in the United States. Identifying donors from whom only
      one kidney was discarded allows us to control for donor traits and better assess
      reasons for organ discard. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      conducted a retrospective cohort study using United Network for Organ Sharing
      Standard Transplant Analysis and Research file data to identify deceased donors
      from whom two kidneys were procured and at least one was transplanted. Unilateral
      pairs were defined as kidney pairs from a single donor from whom one kidney was
      discarded ("unilateral discard") but the other was transplanted ("unilateral
      transplant"). Organ quality was estimated using the Kidney Donor Risk Index and
      Kidney Donor Profile Index (KDPI). We compared all-cause graft failure rates for
      unilateral transplants to those for bilateral transplant Kaplan-Meier methods,
      and life table methodology was used to evaluate 1-, 2-, 3-, and 5-year survival
      rates of transplants from bilateral and unilateral donors. RESULTS: Compared with
      bilateral donors (i.e., both kidneys transplanted) (n=80,584), unilateral donors
      (i.e., only one kidney transplanted) (n=7625) had higher mean terminal creatinine
      (1.3+/-2.1 mg/dl versus 1.1+/-0.9 mg/dl) and KDPI (67%+/-25% versus 42%+/-27%),
      were older, and were more likely to have hypertension, diabetes, hepatitis C,
      terminal stroke, or meet Centers for Disease Control and Prevention high-risk
      donor criteria. Unilateral discards were primarily attributed to factors expected
      to be similar in both kidneys from a donor: biopsy findings (22%), no interested
      recipient (13%), and donor history (7%). Anatomic abnormalities (14%), organ
      damage (11%), and extended ischemia (6%) accounted for about 30% of discards, but
      were the commonest reasons among low KDPI kidneys. Among kidneys with KDPI>=60%,
      there was an incremental difference in allograft survival over time (for
      unilateral versus bilateral transplants, 1-year survival: 83% versus 87%; 3-year
      survival: 69% versus 73%; 5-year survival: 51% versus 58%). CONCLUSIONS: A large
      number of discarded kidneys were procured from donors whose contralateral kidneys
      were transplanted with good post-transplant outcomes.

PMID- 29217538
TI  - Compelling Evidence of the Need for Policy Change to Decrease Deceased Donor
      Kidney Discard in the United States: Waste Not Want Less.

PMID- 29217539
TI  - Inhibition of Cocaine and 3,4-Methylenedioxypyrovalerone (MDPV) Self
      Administration by Lorcaserin Is Mediated by 5-HT2C Receptors in Rats.
AB  - Lorcaserin is a serotonin (5-HT)2C receptor-preferring agonist approved by the US
      Food and Drug Administration to treat obesity. Lorcaserin decreases cocaine self
      administration in rats and monkeys. Although this effect is partially inhibited
      by a 5-HT2C receptor antagonist (SB242084), lorcaserin also has effects at 5-HT2A
      and 5-HT1A receptors, and the relative contribution of these receptors to its
      anti-cocaine effects has not been investigated. The goals of this study were to
      determine 1) the potency and effectiveness of lorcaserin to decrease self
      administration of cocaine and 3,4-methylenedioxypyrovalerone (MDPV), a common
      "bath salts" constituent; and 2) the receptor(s) mediating the effects of
      lorcaserin on cocaine and MDPV self-administration. Male Sprague-Dawley rats (n =
      6) were trained to self-administer MDPV under a progressive ratio schedule of
      reinforcement and maintained under this schedule with daily access to 0.32 mg/kg
      per infusion of cocaine or 0.032 mg/kg per infusion of MDPV. Dose-response curves
      for the effects of lorcaserin on cocaine and MDPV self-administration were
      generated by administering lorcaserin (0.1-5.6 mg/kg) 25 minutes before the start
      of the session. To assess the effects of 5-HT2C (SB242084, 0.1 mg/kg), 5-HT2A
      (MDL100907, 0.1 mg/kg), and 5-HT1A (WAY100635, 0.178 mg/kg) receptor antagonists,
      they were administered 15 minutes before lorcaserin. Lorcaserin decreased cocaine
      and MDPV self-administration with equal potency. Antagonism of 5-HT2C (but not 5
      HT1A or 5-HT2A) receptors blocked the effects of lorcaserin on cocaine and MDPV
      self-administration. Taken together, these data provide additional support for
      further development of 5-HT2C receptor agonists, such as lorcaserin, for the
      treatment of stimulant abuse.

PMID- 29217540
TI  - Cancer Stem Cell-Suppressing Activity of Chrysotoxine, a Bibenzyl from Dendrobium
      pulchellum.
AB  - Cancer stem cells (CSCs) have been recognized as rare populations driving cancer
      progression, metastasis, and drug resistance in leading cancers. Attempts have
      been made toward identifying compounds that specifically target these CSCs.
      Therefore, investigations of novel therapeutic strategies for CSC targeting are
      required. The cytotoxic effects of chrysotoxine on human non-small cell lung
      cancer-derived H460 and H23 cells were evaluated by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. The effects of chrysotoxine
      suppression of CSC-like phenotypes were determined in CSC-rich populations and
      primary CSCs in three-dimensional (3D) culture and in an extreme limiting
      dilution assay. Expression of CSC markers and associated proteins was determined
      by Western blot analyse and flow cytometry. We have reported herein the CSC
      suppressing activity of chrysotoxine, a bibenzyl compound isolated from
      Dendrobium pulchellum We have shown, to our knowledge for the first time, that
      chrysotoxine dramatically suppresses CSC-like phenotypes of H460 and H23 cells.
      Treatment with chrysotoxine significantly reduced the viability of 3D CSC-rich
      populations and concomitantly decreased known CSC markers. Chrysotoxine
      suppressed CSC phenotypes through downregulation of Src/protein kinase B (Akt)
      signaling. Active (phosphorylated Y416) Src was shown to regulate cancer
      stemness, since ectopic overexpression of Src strongly activated Akt and
      subsequently enhanced pluripotency transcription factor SRY (sex-determining
      region Y)-box 2 (Sox2)- mediating CSC phenotypes, whereas the short hairpin RNA
      of Src and an Src inhibitor (dasatinib) suppressed Akt, Sox2, and CSC properties.
      Importantly, chrysotoxine was shown to suppress active Src/Akt signaling and in
      turn depleted Sox2-mediated CSCs. Our findings indicate a novel CSC-targeted role
      of chrysotoxine and its regulation by Src/Akt and Sox2, which may be exploited
      for cancer treatment.

PMID- 29217541
TI  - Designing river flows to improve food security futures in the Lower Mekong Basin.
AB  - Rivers provide unrivaled opportunity for clean energy via hydropower, but little
      is known about the potential impact of dam-building on the food security these
      rivers provide. In tropical rivers, rainfall drives a periodic flood pulse
      fueling fish production and delivering nutrition to more than 150 million people
      worldwide. Hydropower will modulate this flood pulse, thereby threatening food
      security. We identified variance components of the Mekong River flood pulse that
      predict yield in one of the largest freshwater fisheries in the world. We used
      these variance components to design an algorithm for a managed hydrograph to
      explore future yields. This algorithm mimics attributes of discharge variance
      that drive fishery yield: prolonged low flows followed by a short flood pulse.
      Designed flows increased yield by a factor of 3.7 relative to historical
      hydrology. Managing desired components of discharge variance will lead to greater
      efficiency in the Lower Mekong Basin food system.

PMID- 29217542
TI  - Comment on "Cognition-mediated evolution of low-quality floral nectars".
AB  - Nachev et al (Reports, 6 January 2017, p. 75) present dilute nectar in bat
      pollinated plants as "paradoxical" because bats prefer concentrated nectar, but
      paradox disappears with realistic assumptions about nectar evolution. We argue
      that they make unrealistic assumptions about the cognitive abilities of bat
      pollinators, invoke Weber's law inappropriately, and cannot predict observed
      nectar concentrations of bat flowers or negative correlations between pollinator
      body size and average concentration.

PMID- 29217543
TI  - Response to Comment on "Cognition-mediated evolution of low-quality floral
      nectars".
AB  - Pyke and Waser claim that our virtual pollination ecology model makes unrealistic
      assumptions and fails to predict observed nectar concentrations of bat flowers
      and negative correlations between pollinator body size and sugar concentration.
      In their comment, crucial model features are misrepresented, misunderstood, or
      ignored. Sensitivity to the supply/demand ratio explains both the equilibrium
      concentrations and the selection for lower concentrations by larger pollinators.

PMID- 29217544
TI  - On the origin of modern humans: Asian perspectives.
AB  - The traditional "out of Africa" model, which posits a dispersal of modern Homo
      sapiens across Eurasia as a single wave at ~60,000 years ago and the subsequent
      replacement of all indigenous populations, is in need of revision. Recent
      discoveries from archaeology, hominin paleontology, geochronology, genetics, and
      paleoenvironmental studies have contributed to a better understanding of the Late
      Pleistocene record in Asia. Important findings highlighted here include growing
      evidence for multiple dispersals predating 60,000 years ago in regions such as
      southern and eastern Asia. Modern humans moving into Asia met Neandertals,
      Denisovans, mid-Pleistocene Homo, and possibly H. floresiensis, with some degree
      of interbreeding occurring. These early human dispersals, which left at least
      some genetic traces in modern populations, indicate that later replacements were
      not wholesale.

PMID- 29217545
TI  - Harassment in science is real.

PMID- 29217548
TI  - NASA sensor to study space junk the size of dust.

PMID- 29217547
TI  - Bioelectronics herald the rise of the cyborg.

PMID- 29217549
TI  - Nations put science before fishing in the Arctic.

PMID- 29217550
TI  - Cuban panel claims stress caused mystery illnesses.

PMID- 29217551
TI  - To help save the heart, is it time to retire cholesterol tests?

PMID- 29217552
TI  - Science groups urge changes as Congress nears final tax bill.

PMID- 29217553
TI  - Last stands.

PMID- 29217554
TI  - Can dams be designed for sustainability?

PMID- 29217555
TI  - Putting the RuBisCO pieces together.

PMID- 29217556
TI  - Coherent nanoparticles in calcite.

PMID- 29217557
TI  - TRP'ing up chronic kidney disease.

PMID- 29217558
TI  - Concerns for ozone recovery.

PMID- 29217559
TI  - Saving lives by regulating guns: Evidence for policy.

PMID- 29217560
TI  - EU can help Spain's endangered seabird.

PMID- 29217561
TI  - Broad conservation: Protect the unknowns.

PMID- 29217562
TI  - Quake warning funds on shaky ground.

PMID- 29217563
TI  - Probing the metabolism of microorganisms.

PMID- 29217564
TI  - Metabolic markers as cancer clues.

PMID- 29217565
TI  - Reading the genome like a history book.

PMID- 29217566
TI  - Biology and physics rendezvous at the membrane.

PMID- 29217567
TI  - Plant RuBisCo assembly in E. coli with five chloroplast chaperones including
      BSD2.
AB  - Plant RuBisCo, a complex of eight large and eight small subunits, catalyzes the
      fixation of CO2 in photosynthesis. The low catalytic efficiency of RuBisCo
      provides strong motivation to reengineer the enzyme with the goal of increasing
      crop yields. However, genetic manipulation has been hampered by the failure to
      express plant RuBisCo in a bacterial host. We achieved the functional expression
      of Arabidopsis thaliana RuBisCo in Escherichia coli by coexpressing multiple
      chloroplast chaperones. These include the chaperonins Cpn60/Cpn20, RuBisCo
      accumulation factors 1 and 2, RbcX, and bundle-sheath defective-2 (BSD2). Our
      structural and functional analysis revealed the role of BSD2 in stabilizing an
      end-state assembly intermediate of eight RuBisCo large subunits until the small
      subunits become available. The ability to produce plant RuBisCo recombinantly
      will facilitate efforts to improve the enzyme through mutagenesis.

PMID- 29217568
TI  - Attosecond-resolved photoionization of chiral molecules.
AB  - Chiral light-matter interactions have been investigated for two centuries,
      leading to the discovery of many chiroptical processes used for discrimination of
      enantiomers. Whereas most chiroptical effects result from a response of bound
      electrons, photoionization can produce much stronger chiral signals that manifest
      as asymmetries in the angular distribution of the photoelectrons along the light
      propagation axis. We implemented self-referenced attosecond photoelectron
      interferometry to measure the temporal profile of the forward and backward
      electron wave packets emitted upon photoionization of camphor by circularly
      polarized laser pulses. We measured a delay between electrons ejected forward and
      backward, which depends on the ejection angle and reaches 24 attoseconds. The
      asymmetric temporal shape of electron wave packets emitted through an
      autoionizing state further reveals the chiral character of strongly correlated
      electronic dynamics.

PMID- 29217569
TI  - Coherently aligned nanoparticles within a biogenic single crystal: A biological
      prestressing strategy.
AB  - In contrast to synthetic materials, materials produced by organisms are formed in
      ambient conditions and with a limited selection of elements. Nevertheless, living
      organisms reveal elegant strategies for achieving specific functions, ranging
      from skeletal support to mastication, from sensors and defensive tools to optical
      function. Using state-of-the-art characterization techniques, we present a
      biostrategy for strengthening and toughening the otherwise brittle calcite
      optical lenses found in the brittlestar Ophiocoma wendtii This intriguing process
      uses coherent nanoprecipitates to induce compressive stresses on the host matrix,
      functionally resembling the Guinier-Preston zones known in classical metallurgy.
      We believe that these calcitic nanoparticles, being rich in magnesium, segregate
      during or just after transformation from amorphous to crystalline phase,
      similarly to segregation behavior from a supersaturated quenched alloy.

PMID- 29217571
TI  - Imaging resonant dissipation from individual atomic defects in graphene.
AB  - Conversion of electric current into heat involves microscopic processes that
      operate on nanometer length scales and release minute amounts of power. Although
      central to our understanding of the electrical properties of materials,
      individual mediators of energy dissipation have so far eluded direct observation.
      Using scanning nanothermometry with submicrokelvin sensitivity, we visualized and
      controlled phonon emission from individual atomic-scale defects in graphene. The
      inferred electron-phonon "cooling power spectrum" exhibits sharp peaks when the
      Fermi level comes into resonance with electronic quasi-bound states at such
      defects. Rare in the bulk but abundant at graphene's edges, switchable atomic
      scale phonon emitters provide the dominant dissipation mechanism. Our work offers
      insights for addressing key materials challenges in modern electronics and
      enables control of dissipation at the nanoscale.

PMID- 29217570
TI  - A precise measurement of the magnetic field in the corona of the black hole
      binary V404 Cygni.
AB  - Observations of binary stars containing an accreting black hole or neutron star
      often show x-ray emission extending to high energies (>10 kilo--electron volts),
      which is ascribed to an accretion disk corona of energetic particles akin to
      those seen in the solar corona. Despite their ubiquity, the physical conditions
      in accretion disk coronae remain poorly constrained. Using simultaneous infrared,
      optical, x-ray, and radio observations of the Galactic black hole system V404
      Cygni, showing a rapid synchrotron cooling event in its 2015 outburst, we present
      a precise 461 +/- 12 gauss magnetic field measurement in the corona. This
      measurement is substantially lower than previous estimates for such systems,
      providing constraints on physical models of accretion physics in black hole and
      neutron star binary systems.

PMID- 29217572
TI  - Renewable acrylonitrile production.
AB  - Acrylonitrile (ACN) is a petroleum-derived compound used in resins, polymers,
      acrylics, and carbon fiber. We present a process for renewable ACN production
      using 3-hydroxypropionic acid (3-HP), which can be produced microbially from
      sugars. The process achieves ACN molar yields exceeding 90% from ethyl 3
      hydroxypropanoate (ethyl 3-HP) via dehydration and nitrilation with ammonia over
      an inexpensive titanium dioxide solid acid catalyst. We further describe an
      integrated process modeled at scale that is based on this chemistry and achieves
      near-quantitative ACN yields (98 +/- 2%) from ethyl acrylate. This endothermic
      approach eliminates runaway reaction hazards and achieves higher yields than the
      standard propylene ammoxidation process. Avoidance of hydrogen cyanide as a by
      product also improves process safety and mitigates product handling requirements.

PMID- 29217573
TI  - Quantized chiral edge conduction on domain walls of a magnetic topological
      insulator.
AB  - Electronic ordering in magnetic and dielectric materials forms domains with
      different signs of order parameters. The control of configuration and motion of
      the domain walls (DWs) enables nonvolatile responses against minute external
      fields. Here, we realize chiral edge states (CESs) on the magnetic DWs of a
      magnetic topological insulator. We design and fabricate the magnetic domains in
      the quantum anomalous Hall state with the tip of a magnetic force microscope and
      prove the existence of the chiral one-dimensional edge conduction along the
      prescribed DWs through transport measurements. The proof-of-concept devices based
      on reconfigurable CESs and Landauer-Buttiker formalism are realized for multiple
      domain configurations with well-defined DW channels. Our results may lead to the
      realization of low-power-consumption spintronic devices.

PMID- 29217574
TI  - Signatures of exciton condensation in a transition metal dichalcogenide.
AB  - Bose condensation has shaped our understanding of macroscopic quantum phenomena,
      having been realized in superconductors, atomic gases, and liquid helium.
      Excitons are bosons that have been predicted to condense into either a superfluid
      or an insulating electronic crystal. Using the recently developed technique of
      momentum-resolved electron energy-loss spectroscopy (M-EELS), we studied
      electronic collective modes in the transition metal dichalcogenide semimetal 1T
      TiSe2 Near the phase-transition temperature (190 kelvin), the energy of the
      electronic mode fell to zero at nonzero momentum, indicating dynamical slowing of
      plasma fluctuations and crystallization of the valence electrons into an exciton
      condensate. Our study provides compelling evidence for exciton condensation in a
      three-dimensional solid and establishes M-EELS as a versatile technique sensitive
      to valence band excitations in quantum materials.

PMID- 29217576
TI  - Firearms and accidental deaths: Evidence from the aftermath of the Sandy Hook
      school shooting.
AB  - Exposure to firearms increased substantially after the December 2012 shooting at
      Sandy Hook Elementary School in Newtown, Connecticut, where 20 children and 6
      adults were killed. Gun sales spiked by 3 million, on the basis of the increase
      in the number of background checks for firearm purchases. Google searches for
      buying and cleaning guns increased. We used Vital Statistics mortality data to
      examine whether a spike in accidental firearm deaths occurred at the same time as
      the greater exposure to firearms. We also assessed whether the increase in these
      deaths was larger in those states where the spike in gun sales per capita was
      larger. We find that an additional 60 deaths overall, including 20 children,
      resulted from unintentional shootings in the immediate aftermath of Sandy Hook.

PMID- 29217575
TI  - Spatiotemporal gene expression trajectories reveal developmental hierarchies of
      the human cortex.
AB  - Systematic analyses of spatiotemporal gene expression trajectories during
      organogenesis have been challenging because diverse cell types at different
      stages of maturation and differentiation coexist in the emerging tissues. We
      identified discrete cell types as well as temporally and spatially restricted
      trajectories of radial glia maturation and neurogenesis in developing human
      telencephalon. These lineage-specific trajectories reveal the expression of
      neurogenic transcription factors in early radial glia and enriched activation of
      mammalian target of rapamycin signaling in outer radial glia. Across cortical
      areas, modest transcriptional differences among radial glia cascade into robust
      typological distinctions among maturing neurons. Together, our results support a
      mixed model of topographical, typological, and temporal hierarchies governing
      cell-type diversity in the developing human telencephalon, including distinct
      excitatory lineages emerging in rostral and caudal cerebral cortex.

PMID- 29217577
TI  - Paradoxical escape responses by narwhals (Monodon monoceros).
AB  - Until recent declines in Arctic sea ice levels, narwhals (Monodon monoceros) have
      lived in relative isolation from human perturbation and sustained predation
      pressures. The resulting naivety has made this cryptic, deep-diving cetacean
      highly susceptible to disturbance, although quantifiable effects have been
      lacking. We deployed a submersible, animal-borne electrocardiograph-accelerometer
      depth recorder to monitor physiological and behavioral responses of East
      Greenland narwhals after release from net entanglement and stranding. Escaping
      narwhals displayed a paradoxical cardiovascular down-regulation (extreme
      bradycardia with heart rate <=4 beats per minute) superimposed on exercise up
      regulation (stroke frequency >25 strokes per minute and energetic costs three to
      six times the resting rate of energy expenditure) that rapidly depleted onboard
      oxygen stores. We attribute this unusual reaction to opposing cardiovascular
      signals-from diving, exercise, and neurocognitive fear responses-that challenge
      physiological homeostasis.

PMID- 29217580
TI  - An unexpected career resource.

PMID- 29217578
TI  - A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney
      disease in animal models.
AB  - Progressive kidney diseases are often associated with scarring of the kidney's
      filtration unit, a condition called focal segmental glomerulosclerosis (FSGS).
      This scarring is due to loss of podocytes, cells critical for glomerular
      filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS
      are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel
      activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity
      mediates FSGS onset and progression is unknown. We identified a small molecule,
      AC1903, that specifically blocks TRPC5 channel activity in glomeruli of
      proteinuric rats. Chronic administration of AC1903 suppressed severe proteinuria
      and prevented podocyte loss in a transgenic rat model of FSGS. AC1903 also
      provided therapeutic benefit in a rat model of hypertensive proteinuric kidney
      disease. These data indicate that TRPC5 activity drives disease and that TRPC5
      inhibitors may be valuable for the treatment of progressive kidney diseases.

PMID- 29217579
TI  - Structural basis for methylphosphonate biosynthesis.
AB  - Methylphosphonate synthase (MPnS) produces methylphosphonate, a metabolic
      precursor to methane in the upper ocean. Here, we determine a 2.35-angstrom
      resolution structure of MPnS and discover that it has an unusual 2-histidine-1
      glutamine iron-coordinating triad. We further solve the structure of a related
      enzyme, hydroxyethylphosphonate dioxygenase from Streptomyces albus (SaHEPD), and
      find that it displays the same motif. SaHEPD can be converted into an MPnS by
      mutation of glutamine-adjacent residues, identifying the molecular requirements
      for methylphosphonate synthesis. Using these sequence markers, we find numerous
      putative MPnSs in marine microbiomes and confirm that MPnS is present in the
      abundant Pelagibacter ubique. The ubiquity of MPnS-containing microbes supports
      the proposal that methylphosphonate is a source of methane in the upper, aerobic
      ocean, where phosphorus-starved microbes catabolize methylphosphonate for its
      phosphorus.

PMID- 29217581
TI  - Structure of the human TRPM4 ion channel in a lipid nanodisc.
AB  - Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed
      cation channel associated with a variety of cardiovascular disorders. TRPM4 is
      activated by increased intracellular calcium in a voltage-dependent manner but,
      unlike many other TRP channels, is permeable to monovalent cations only. Here we
      present two structures of full-length human TRPM4 embedded in lipid nanodiscs at
      ~3-angstrom resolution, as determined by single-particle cryo-electron
      microscopy. These structures, with and without calcium bound, reveal a general
      architecture for this major subfamily of TRP channels and a well-defined calcium
      binding site within the intracellular side of the S1-S4 domain. The structures
      correspond to two distinct closed states. Calcium binding induces conformational
      changes that likely prime the channel for voltage-dependent opening.

PMID- 29217582
TI  - Spatial reconstruction of immune niches by combining photoactivatable reporters
      and scRNA-seq.
AB  - Cellular functions are strongly dependent on surrounding cells and environmental
      factors. Current technologies are limited in their ability to characterize the
      spatial location and gene programs of cells in poorly structured and dynamic
      niches. We developed a method, NICHE-seq, that combines photoactivatable
      fluorescent reporters, two-photon microscopy, and single-cell RNA sequencing
      (scRNA-seq) to infer the cellular and molecular composition of niches. We applied
      NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq
      is highly reproducible in spatial tissue reconstruction, enabling identification
      of rare niche-specific immune subpopulations and gene programs, including natural
      killer cells within infected B cell follicles and distinct myeloid states in the
      spleen and tumor. This study establishes NICHE-seq as a broadly applicable method
      for elucidating high-order spatial organization of cell types and their molecular
      pathways.

PMID- 29217583
TI  - Structure of the cold- and menthol-sensing ion channel TRPM8.
AB  - Transient receptor potential melastatin (TRPM) cation channels are polymodal
      sensors that are involved in a variety of physiological processes. Within the
      TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans.
      We determined the cryo-electron microscopy structure of the full-length TRPM8
      from the collared flycatcher at an overall resolution of ~4.1 angstroms. Our
      TRPM8 structure reveals a three-layered architecture. The amino-terminal domain
      with a fold distinct among known TRP structures, together with the carboxyl
      terminal region, forms a large two-layered cytosolic ring that extensively
      interacts with the transmembrane channel layer. The structure suggests that the
      menthol-binding site is located within the voltage-sensor-like domain and thus
      provides a structural glimpse of the design principle of the molecular transducer
      for cold and menthol sensation.

PMID- 29217584
TI  - Aging and neurodegeneration are associated with increased mutations in single
      human neurons.
AB  - It has long been hypothesized that aging and neurodegeneration are associated
      with somatic mutation in neurons; however, methodological hurdles have prevented
      testing this hypothesis directly. We used single-cell whole-genome sequencing to
      perform genome-wide somatic single-nucleotide variant (sSNV) identification on
      DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15
      normal individuals (aged 4 months to 82 years), as well as 9 individuals affected
      by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne
      syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with
      age in both areas (with a higher rate in hippocampus) and were more abundant in
      neurodegenerative disease. The accumulation of somatic mutations with age-which
      we term genosenium-shows age-related, region-related, and disease-related
      molecular signatures and may be important in other human age-associated
      conditions.

PMID- 29217586
TI  - Resonantly driven CNOT gate for electron spins.
AB  - Single-qubit rotations and two-qubit CNOT operations are crucial ingredients for
      universal quantum computing. Although high-fidelity single-qubit operations have
      been achieved using the electron spin degree of freedom, realizing a robust CNOT
      gate has been challenging because of rapid nuclear spin dephasing and charge
      noise. We demonstrate an efficient resonantly driven CNOT gate for electron spins
      in silicon. Our platform achieves single-qubit rotations with fidelities greater
      than 99%, as verified by randomized benchmarking. Gate control of the exchange
      coupling allows a quantum CNOT gate to be implemented with resonant driving in
      ~200 nanoseconds. We used the CNOT gate to generate a Bell state with 78%
      fidelity (corrected for errors in state preparation and measurement). Our quantum
      dot device architecture enables multi-qubit algorithms in silicon.

PMID- 29217585
TI  - Patient HLA class I genotype influences cancer response to checkpoint blockade
      immunotherapy.
AB  - CD8+ T cell-dependent killing of cancer cells requires efficient presentation of
      tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the
      extent to which patient-specific HLA-I genotype influences response to anti
      programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein
      4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer
      patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at
      HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with
      patients who were homozygous for at least one HLA locus. In two independent
      melanoma cohorts, patients with the HLA-B44 supertype had extended survival,
      whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of
      heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics
      simulations of HLA-B*15:01 revealed different elements that may impair CD8+ T
      cell recognition of neoantigens. Our results have important implications for
      predicting response to ICB and for the design of neoantigen-based therapeutic
      vaccines.

PMID- 29217587
TI  - Different mutational rates and mechanisms in human cells at pregastrulation and
      neurogenesis.
AB  - Somatic mosaicism in the human brain may alter function of individual neurons. We
      analyzed genomes of single cells from the forebrains of three human fetuses (15
      to 21 weeks postconception) using clonal cell populations. We detected 200 to 400
      single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found
      in cancer cell genomes, indicating a role of background mutagenesis in cancer.
      SNVs with a frequency of >2% in brain were also present in the spleen, revealing
      a pregastrulation origin. We reconstructed cell lineages for the first five
      postzygotic cleavages and calculated a mutation rate of ~1.3 mutations per
      division per cell. Later in development, during neurogenesis, the mutation
      spectrum shifted toward oxidative damage, and the mutation rate increased. Both
      neurogenesis and early embryogenesis exhibit substantially more mutagenesis than
      adulthood.

PMID- 29217588
TI  - Tax plans and science.

PMID- 29217589
TI  - Cohesin: building loops, but not compartments.

PMID- 29217590
TI  - A mechanism of cohesin-dependent loop extrusion organizes zygotic genome
      architecture.
AB  - Fertilization triggers assembly of higher-order chromatin structure from a
      condensed maternal and a naive paternal genome to generate a totipotent embryo.
      Chromatin loops and domains have been detected in mouse zygotes by single-nucleus
      Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when and how embryonic
      chromatin conformations are assembled. Here, we investigated whether a mechanism
      of cohesin-dependent loop extrusion generates higher-order chromatin structures
      within the one-cell embryo. Using snHi-C of mouse knockout embryos, we
      demonstrate that the zygotic genome folds into loops and domains that critically
      depend on Scc1-cohesin and that are regulated in size and linear density by Wapl.
      Remarkably, we discovered distinct effects on maternal and paternal chromatin
      loop sizes, likely reflecting differences in loop extrusion dynamics and
      epigenetic reprogramming. Dynamic polymer models of chromosomes reproduce changes
      in snHi-C, suggesting a mechanism where cohesin locally compacts chromatin by
      active loop extrusion, whose processivity is controlled by Wapl. Our simulations
      and experimental data provide evidence that cohesin-dependent loop extrusion
      organizes mammalian genomes over multiple scales from the one-cell embryo onward.

PMID- 29217592
TI  - Loss of LOFSEP Transcription Factor Function Converts Spikelet to Leaf-Like
      Structures in Rice.
AB  - SEPALLATA (SEP)-like genes, which encode a subfamily of MADS-box transcription
      factors, are essential for specifying floral organ and meristem identity in
      angiosperms. Rice (Oryza sativa) has five SEP-like genes with partial redundancy
      and overlapping expression domains, yet their functions and evolutionary
      conservation are only partially known. Here, we describe the biological role of
      one of the SEP genes of rice, OsMADS5, in redundantly controlling spikelet
      morphogenesis. OsMADS5 belongs to the conserved LOFSEP subgroup along with
      OsMADS1 and OsMADS34OsMADS5 was expressed strongly across a broad range of
      reproductive stages and tissues. No obvious phenotype was observed in the osmads5
      single mutants when compared with the wild type, which was largely due to the
      functional redundancy among the three LOFSEP genes. Genetic and molecular
      analyses demonstrated that OsMADS1, OsMADS5, and OsMADS34 together regulate
      floral meristem determinacy and specify the identities of spikelet organs by
      positively regulating the other MADS-box floral homeotic genes. Experiments
      conducted in yeast also suggested that OsMADS1, OsMADS5, and OsMADS34 form
      protein-protein interactions with other MADS-box floral homeotic members, which
      seems to be a typical, conserved feature of plant SEP proteins.

PMID- 29217591
TI  - Topologically associating domains and chromatin loops depend on cohesin and are
      regulated by CTCF, WAPL, and PDS5 proteins.
AB  - Mammalian genomes are spatially organized into compartments, topologically
      associating domains (TADs), and loops to facilitate gene regulation and other
      chromosomal functions. How compartments, TADs, and loops are generated is
      unknown. It has been proposed that cohesin forms TADs and loops by extruding
      chromatin loops until it encounters CTCF, but direct evidence for this hypothesis
      is missing. Here, we show that cohesin suppresses compartments but is required
      for TADs and loops, that CTCF defines their boundaries, and that the cohesin
      unloading factor WAPL and its PDS5 binding partners control the length of loops.
      In the absence of WAPL and PDS5 proteins, cohesin forms extended loops,
      presumably by passing CTCF sites, accumulates in axial chromosomal positions
      (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also
      required for boundary function. These results show that cohesin has an essential
      genome-wide function in mediating long-range chromatin interactions and support
      the hypothesis that cohesin creates these by loop extrusion, until it is delayed
      by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA
      by WAPL.

PMID- 29217593
TI  - Suboptimal Acclimation of Photosynthesis to Light in Wheat Canopies.
AB  - Photosynthetic acclimation (photoacclimation) is the process whereby leaves alter
      their morphology and/or biochemistry to optimize photosynthetic efficiency and
      productivity according to long-term changes in the light environment. The three
      dimensional architecture of plant canopies imposes complex light dynamics, but
      the drivers for photoacclimation in such fluctuating environments are poorly
      understood. A technique for high-resolution three-dimensional reconstruction was
      combined with ray tracing to simulate a daily time course of radiation profiles
      for architecturally contrasting field-grown wheat (Triticum aestivum) canopies.
      An empirical model of photoacclimation was adapted to predict the optimal
      distribution of photosynthesis according to the fluctuating light patterns
      throughout the canopies. While the photoacclimation model output showed good
      correlation with field-measured gas-exchange data at the top of the canopy, it
      predicted a lower optimal light-saturated rate of photosynthesis at the base.
      Leaf Rubisco and protein contents were consistent with the measured optimal light
      saturated rate of photosynthesis. We conclude that, although the photosynthetic
      capacity of leaves is high enough to exploit brief periods of high light within
      the canopy (particularly toward the base), the frequency and duration of such
      sunflecks are too small to make acclimation a viable strategy in terms of carbon
      gain. This suboptimal acclimation renders a large portion of residual
      photosynthetic capacity unused and reduces photosynthetic nitrogen use efficiency
      at the canopy level, with further implications for photosynthetic productivity.
      It is argued that (1) this represents an untapped source of photosynthetic
      potential and (2) canopy nitrogen could be lowered with no detriment to carbon
      gain or grain protein content.

PMID- 29217594
TI  - Glucose-Induced Trophic Shift in an Endosymbiont Dinoflagellate with
      Physiological and Molecular Consequences.
AB  - Interactions between the dinoflagellate endosymbiont Symbiodinium and its
      cnidarian hosts (e.g. corals, sea anemones) are the foundation of coral-reef
      ecosystems. Carbon flow between the partners is a hallmark of this mutualism, but
      the mechanisms governing this flow and its impact on symbiosis remain poorly
      understood. We showed previously that although Symbiodinium strain SSB01 can grow
      photoautotrophically, it can grow mixotrophically or heterotrophically when
      supplied with Glc, a metabolite normally transferred from the alga to its host.
      Here we show that Glc supplementation of SSB01 cultures causes a loss of
      pigmentation and photosynthetic activity, disorganization of thylakoid membranes,
      accumulation of lipid bodies, and alterations of cell-surface morphology. We used
      global transcriptome analyses to determine if these physiological changes were
      correlated with changes in gene expression. Glc-supplemented cells exhibited a
      marked reduction in levels of plastid transcripts encoding photosynthetic
      proteins, although most nuclear-encoded transcripts (including those for proteins
      involved in lipid synthesis and formation of the extracellular matrix) exhibited
      little change in their abundances. However, the altered carbon metabolism in Glc
      supplemented cells was correlated with modest alterations (approximately 2x) in
      the levels of some nuclear-encoded transcripts for sugar transporters. Finally,
      Glc-bleached SSB01 cells appeared unable to efficiently populate anemone larvae.
      Together, these results suggest links between energy metabolism and cellular
      physiology, morphology, and symbiotic interactions. However, the results also
      show that in contrast to many other organisms, Symbiodinium can undergo dramatic
      physiological changes that are not reflected by major changes in the abundances
      of nuclear-encoded transcripts and thus presumably reflect posttranscriptional
      regulatory processes.

PMID- 29217595
TI  - Preferential Distribution of Boron to Developing Tissues Is Mediated by the
      Intrinsic Protein OsNIP3.
AB  - Boron is especially required for the growth of meristem and reproductive organs,
      but the molecular mechanisms underlying the preferential distribution of B to
      these developing tissues are poorly understood. Here, we show evidence that a
      member of nodulin 26-like intrinsic protein (NIP), OsNIP3;1, is involved in this
      preferential distribution in rice (Oryza sativa). OsNIP3;1 was highly expressed
      in the nodes and its expression was up-regulated by B deficiency, but down
      regulated by high B. OsNIP3;1 was polarly localized at the xylem parenchyma cells
      of enlarged vascular bundles of nodes facing toward the xylem vessels.
      Furthermore, this protein was rapidly degraded within a few hours in response to
      high B. Knockout of this gene hardly affected the uptake and root-to-shoot
      translocation of B, but altered B distribution in different organs in the above
      ground parts, decreased distribution of B to the new leaves, and increased
      distribution to the old leaves. These results indicate that OsNIP3;1 located in
      the nodes is involved in the preferential distribution of B to the developing
      tissues by unloading B from the xylem in rice and that it is regulated at both
      transcriptional and protein level in response to external B level.

PMID- 29217597
TI  - Outcomes in coronary artery disease patients with sleepy obstructive sleep apnoea
      on CPAP.
AB  - Coronary artery disease (CAD) patients with obstructive sleep apnoea (OSA) have
      increased risk for major adverse cardiovascular and cerebrovascular events
      (MACCEs) compared with CAD patients without OSA. We aimed to address if the risk
      is similar in both groups when OSA patients are treated.This study was a parallel
      observational arm of the RICCADSA randomised controlled trial, conducted in
      Sweden between 2005 and 2013. Patients with revascularised CAD and OSA (apnoea
      hypopnoea index (AHI) >=15 events.h-1) with daytime sleepiness (Epworth
      Sleepiness Scale score >=10) were offered continuous positive airway pressure
      (CPAP) (n=155); CAD patients with no OSA (AHI <5 events.h-1) acted as controls
      (n=112), as a randomisation of sleepy OSA patients to no treatment would not be
      ethically feasible. The primary end-point was the first event of MACCEs. Median
      follow-up was 57 months.The incidence of MACCEs was 23.2% in OSA patients versus
      16.1% in those with no OSA (adjusted hazard ratio 0.96, 95% CI 0.40-2.31;
      p=0.923). Age and previous revascularisation were associated with increased risk
      for MACCEs, whereas coronary artery bypass grafting at baseline was associated
      with reduced risk.We conclude that the risk for MACCEs was not increased in CAD
      patients with sleepy OSA on CPAP compared with patients without OSA.

PMID- 29217596
TI  - Seedling Establishment: A Dimmer Switch-Regulated Process between Dark and Light
      Signaling.

PMID- 29217599
TI  - ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old
      children.
AB  - The present statement was produced by a European Respiratory Society Task Force
      to summarise the evidence and current practice on the diagnosis and management of
      obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A
      systematic literature search was completed and 159 articles were summarised to
      answer clinically relevant questions. SDB is suspected when symptoms or
      abnormalities related to upper airway obstruction are identified. Morbidity
      (pulmonary hypertension, growth delay, behavioural problems) and coexisting
      conditions (feeding difficulties, recurrent otitis media) may be present. SDB
      severity is measured objectively, preferably by polysomnography, or alternatively
      polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction
      during wakefulness, those with abnormal sleep study in combination with SDB
      symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular
      hypoplasia) as well as children with SDB and complex conditions (e.g. Down
      syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy
      and continuous positive airway pressure are the most frequently used treatment
      measures along with interventions targeting specific conditions (e.g.
      supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular
      hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a
      multifactorial disorder that requires objective assessment and treatment of all
      underlying abnormalities that contribute to upper airway obstruction during
      sleep.

PMID- 29217598
TI  - Phenotypes of symptomatic airways disease in China and New Zealand.
AB  - It is uncertain whether phenotypes of asthma and chronic obstructive pulmonary
      disease (COPD) vary between populations with different genetic and environmental
      characteristics. Here, our objective was to compare the phenotypes of airways
      disease in two separate populations.This was a cross-sectional observational
      study in adult populations from New Zealand and China. Participants aged 40-75
      years who reported wheeze and breathlessness in the last 12 months were randomly
      selected from the general population and underwent detailed characterisation.
      Complete data for cluster analysis were available for 345 participants.
      Hierarchical cluster analysis was undertaken, based on 12 variables: forced
      expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio, bronchodilator
      reversibility, peak expiratory flow variability, transfer coefficient of the lung
      for carbon monoxide, exhaled nitric oxide fraction, total IgE, C-reactive
      protein, age of symptom onset, body mass index, health status and cigarette smoke
      exposure.Cluster analysis of the combined dataset described five phenotypes:
      "severe late-onset asthma/COPD overlap group", "moderately severe early-onset
      asthma/COPD overlap group", "moderate to severe asthma group with type 2
      predominant disease", and two groups with minimal airflow obstruction,
      differentiated by age of onset. Separate analyses by country showed similar
      patterns; however, a distinct obese/comorbid group was observed in the New
      Zealand population.Cluster analysis of adults with symptomatic airways disease
      suggests the presence of similar asthma/COPD overlap phenotypes within
      populations with different genetic and environmental characteristics, and an
      obese/comorbid phenotype in a Western population.

PMID- 29217600
TI  - Asthma phenotypes: do cough and wheeze predict exacerbations in persistent
      asthma?
AB  - Little is known of the long-term symptom profile in uncontrolled asthma and
      whether symptoms can predict distinct phenotypes. The primary objective of these
      analyses was to assess diurnal profile of cough and wheeze in an uncontrolled
      asthma population. Secondary outcomes were to examine how these symptom profiles
      influence response to treatment.Twice-daily electronically recorded data from
      1701 patients were examined in relation to the population demographics. Reliever
      treatment with salbutamol was then compared with extra-fine
      beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation
      frequency was then correlated with the symptom profile.Symptoms were commoner in
      older patients with an increased body mass index. In most patients, reported
      cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and
      wheeze-predominant patients were identified; the former were overweight, older
      females and the latter older males. Diurnal symptoms of cough and wheeze were
      similarly attenuated by both therapies. MART reduced exacerbation frequency by a
      third compared with salbutamol, and this effect was greatest in patients with
      fewest reported symptoms.While cough and wheeze are highly correlated in
      uncontrolled asthma, some patients predominantly have cough whereas others
      wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting
      an alternative pathophysiology. MART may be the preferred option in those with
      fewest symptoms.

PMID- 29217601
TI  - Novel magnetic resonance technique for functional imaging of cystic fibrosis lung
      disease.
AB  - Lung function tests are commonly used to monitor lung disease in cystic fibrosis
      (CF). While practical, they cannot locate the exact origin of functional
      impairment. Contemporary magnetic resonance imaging (MRI) techniques provide
      information on the location of disease but the need for contrast agents
      constrains their repeated application. We examined the correlation between
      functional MRI, performed without administration of contrast agent, and lung
      clearance index (LCI) from nitrogen multiple-breath washout (N2-MBW).40 children
      with CF (median (range) age 12.0 (6-18) years) and 12 healthy age-matched
      controls underwent functional and structural MRI and lung function tests on the
      same day. Functional MRI provided semiquantitative measures of perfusion (RQ) and
      ventilation (RFV) impairment as percentages of affected lung volume.
      Morphological MRI was evaluated using CF-specific scores. LCI measured global
      ventilation inhomogeneity.MRI detected functional impairment in CF: RFV 19-38%
      and RQ 16-35%. RFV and RQ correlated strongly with LCI (r=0.76, p<0.0001 and
      r=0.85, p<0.0001, respectively), as did total morphology score (r=0.81,
      p<0.0001). All indices differed significantly between patients with CF and
      healthy controls (p<0.001).Noninvasive functional MRI is a promising method to
      detect and visualise perfusion and ventilation impairment in CF without the need
      for contrast agents.

PMID- 29217602
TI  - Radiological abnormalities following bronchial thermoplasty: is the
      pathophysiology understood?

PMID- 29217603
TI  - Fluoroquinolone resistance in multidrug-resistant Mycobacterium tuberculosis
      independent of fluoroquinolone use.

PMID- 29217604
TI  - Asthma control and action plans.

PMID- 29217605
TI  - Care pathways for the selection of a biologic in severe asthma.

PMID- 29217606
TI  - Age should not be a barrier for pulmonary endarterectomy in carefully selected
      patients.

PMID- 29217608
TI  - Ten principles for climate, environment and respiratory health.

PMID- 29217607
TI  - Asthma control and action plans.

PMID- 29217609
TI  - Malaria and the development of pulmonary fibrosis.

PMID- 29217610
TI  - Radiological abnormalities following bronchial thermoplasty: is the
      pathophysiology understood?

PMID- 29217613
TI  - Flat foveal contour simulating macular hole.

PMID- 29217612
TI  - Mycobacterium tuberculosis of the elbow joint.
AB  - Mycobacterium tuberculosis(TB) affecting the elbow joint is rarely reported in
      the developed world. We present the case of an 85-year-old Caucasian female who
      complained of a chronically discharging and painful wound across her left elbow
      during her admission for an ischaemic stroke. This was initially deemed to be
      either a bursitis or local manifestation of amyloid by her general practitioner
      and dermatologist respectively prior to admission. She was commenced on
      flucloxacillin by the medical team for presumed cellulitis with minimal response.
      A synovial fluid sample and repeated wound swabs yielded no growth from routine
      bacterial culture. Radiological assessment together with knowledge of her husband
      having previous TB raised the possibility of TB arthritis. Synovial fluid
      aspirate was subsequently sent for acid-alcohol fast bacilli microscopy and
      mycobacterial culture that confirmed M. tuberculosis She was consequently started
      on multidrug TB therapy, over a year after the onset of her symptoms.

PMID- 29217614
TI  - Complication of deep brain stimulation for Parkinson's disease.

PMID- 29217611
TI  - Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study
      of Atherosclerosis (MESA) air-lung study.
AB  - We studied whether ambient air pollution is associated with interstitial lung
      abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and
      quantitative measurements of subclinical interstitial lung disease (ILD) on
      computed tomography (CT).We performed analyses of community-based dwellers
      enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used
      cohort-specific spatio-temporal models to estimate ambient pollution (fine
      particulate matter (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2) and
      ozone (O3)) at each home. A total of 5495 participants underwent serial
      assessment of HAAs by cardiac CT; 2671 participants were assessed for ILAs using
      full lung CT at the 10-year follow-up. We used multivariable logistic regression
      and linear mixed models adjusted for age, sex, ethnicity, education, tobacco use,
      scanner technology and study site.The odds of ILAs increased 1.77-fold per 40 ppb
      increment in NOx (95% CI 1.06 to 2.95, p = 0.03). There was an overall trend
      towards an association between higher exposure to NOx and greater progression of
      HAAs (0.45% annual increase in HAAs per 40 ppb increment in NOx; 95% CI -0.02 to
      0.92, p = 0.06). Associations of ambient fine particulate matter (PM2.5), NOx and
      NO2 concentrations with progression of HAAs varied by race/ethnicity (p = 0.002,
      0.007, 0.04, respectively, for interaction) and were strongest among non-Hispanic
      white people.We conclude that ambient air pollution exposures were associated
      with subclinical ILD.

PMID- 29217615
TI  - Identity, personhood and the law: a response to Ashcroft and McGee.

PMID- 29217616
TI  - Interactome Mapping Uncovers a General Role for Numb in Protein Kinase
      Regulation.
AB  - Cellular functions are frequently regulated by protein-protein interactions
      involving the binding of a modular domain in one protein to a specific peptide
      sequence in another. This mechanism may be explored to identify binding partners
      for proteins harboring a peptide-recognition domain. Here we report a proteomic
      strategy combining peptide and protein microarray screening with biochemical and
      cellular assays to identify modular domain-mediated protein-protein interactions
      in a systematic manner. We applied this strategy to Numb, a multi-functional
      protein containing a phosphotyrosine-binding (PTB) domain. Through the screening
      of a protein microarray, we identified >100 protein kinases, including both Tyr
      and Ser/Thr kinases, that could potentially interact with the Numb PTB domain,
      suggesting a general role for Numb in regulating kinase function. The putative
      interactions between Numb and several tyrosine kinases were subsequently
      validated by GST pull-down and/or co-immunoprecipitation assays. Furthermore,
      using the Oriented Peptide Array Library approach, we defined the specificity of
      the Numb PTB domain which, in turn, allowed us to predict binding partners for
      Numb at the genome level. The combination of the protein microarray screening
      with computer-aided prediction produced the most expansive interactome for Numb
      to date, implicating Numb in regulating phosphorylation signaling through protein
      kinases and phosphatases. Not only does the data generated from this study
      provide an important resource for hypothesis-driven research to further define
      the function of Numb, the proteomic strategy described herein may be employed to
      uncover the interactome for other peptide-recognition domains whose consensus
      motifs are known or can be determined.

PMID- 29217617
TI  - Two-Step Coimmunoprecipitation (TIP) Enables Efficient and Highly Selective
      Isolation of Native Protein Complexes.
AB  - Coimmunoprecipitation (co-IP) is one of the most frequently used techniques to
      study protein-protein (PPIs) or protein-nucleic acid interactions (PNIs).
      However, the presence of coprecipitated contaminants is a well-recognized issue
      associated with single-step co-IPs. To overcome this limitation, we developed the
      two-step co-IP (TIP) strategy that enables sequential coimmunoprecipitations of
      endogenous protein complexes. TIP can be performed with a broad range of mono-
      and polyclonal antibodies targeting a single protein or different components of a
      given complex. TIP results in a highly selective enrichment of protein complexes
      and thus outperforms single-step co-IPs for downstream applications such as mass
      spectrometry for the identification of PPIs and quantitative PCR for the analysis
      of PNIs. We benchmarked TIP for the identification of CD95/FAS-interacting
      proteins in primary human CD4+ T cells, which recapitulated all major known
      interactors, but also enabled the proteomics discovery of PPM1G and IPO7 as new
      interaction partners. For its feasibility and high performance, we propose TIP as
      an advanced tool for the isolation of highly purified protein-protein and protein
      nucleic acid complexes under native expression conditions.

PMID- 29217619
TI  - microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced
      Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor
      Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro.
AB  - Transmissible gastroenteritis virus (TGEV), a member of the coronaviridae family,
      could cause fatal diarrhea of piglets and result in numerous economic losses.
      Previous studies demonstrated that TGEV infection could lead to mitochondrial
      damage and upregulate miR-4331 level. So miR-4331 may play an important
      regulatory role in the control of mitochondrial function. To explore the
      potential role of miR-4331 in mitochondrial damage, we adopted a strategy
      consisting of quantitative proteomic analysis of porcine kidney (PK-15) cells in
      response to miR-4331 and TGEV infection. Eventually, 69 differentially expressed
      proteins were gained. The target of miR-4331 was identified. The effects of miR
      4331 and its target RB1 on mitochondrial Ca2+ level, mitochondrial membrane
      potential (MMP), interleukin-1 receptor accessory protein (IL1RAP), p38 MAPK
      signaling pathway were investigated. The results showed that miR-4331 elevated
      mitochondrial Ca2+ level, reduced MMP, targets Retinoblastoma 1 (RB1),
      upregulated IL1RAP, and induced activation of p38 MAPK pathway during TGEV
      infection. RB1 was identified as the direct targets of miR-4331 and downregulated
      IL1RAP, suppressed the activation of p38 MPAK, and attenuated TGEV-induced
      mitochondrial damage. In addition, IL1RAP played a positive role in activating
      p38 MAPK signaling and negative role in TGEV-induced mitochondrial damage. The
      data indicate that miR-4331 aggravates TGEV-induced mitochondrial damage by
      repressing expression of RB1, promoting IL1RAP, and activating p38 MAPK pathway.

PMID- 29217620
TI  - Risk of second malignant neoplasm and mortality in patients with rheumatoid
      arthritis treated with biological DMARDs: a Danish population-based cohort study.
AB  - OBJECTIVE: To study the risk of a second malignant neoplasm (SMN) and mortality
      in patients with rheumatoid arthritis (RA) with a history of a primary cancer
      diagnosis and treated with biological disease-modifying antirheumatic drugs
      (bDMARD). METHODS: Among patients with RA (n=15 286) registered in the DANBIO
      Register during 2000-2011, 1678 had a primary cancer according to the Danish
      Cancer Registry. HRs for SMN and death were calculated. RESULTS: During follow-up
      there were 279 patients with RA contributing person-years to the bDMARDs use
      before their primary cancer diagnosis, 220 to the only after, 92 to the both
      before and after, while 1203 patients with RA contributed to the non-use strata.
      Ever use of bDMARDs was associated with a HR of 1.11 (95% CI 0.74 to 1.67) for
      developing a SMN compared with non-use (cancer site adjusted). The HR for death
      associated with bDMARD use before the primary cancer diagnosis was increased 1.53
      (95% CI 1.13 to 2.09). After further adjustment for extent of the primary cancer,
      the HR for death was 1.20 (95% CI 0.88 to 1.63) for bDMARDs use before cancer,
      1.36 (95% CI 0.78 to 2.39) for bDMARD use only after cancer and 1.22 (95% CI 0.70
      to 2.13) for use both before and after the cancer. CONCLUSIONS: Among patients
      with RA with a history of cancer, treatment with bDMARDs was not associated with
      increased risk of SMN. No clear conclusion can be drawn regarding mortality in
      bDMARD-treated patients with RA.

PMID- 29217621
TI  - Cardiovascular effects of hydroxychloroquine: a systematic review and meta
      analysis.

PMID- 29217618
TI  - Lipopolysaccharide Upregulates Palmitoylated Enzymes of the Phosphatidylinositol
      Cycle: An Insight from Proteomic Studies.
AB  - Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative
      bacteria that induces strong proinflammatory reactions of mammals. These
      processes are triggered upon sequential binding of LPS to CD14, a GPI-linked
      plasma membrane raft protein, and to the TLR4/MD2 receptor complex. We have found
      earlier that upon LPS binding, CD14 triggers generation of phosphatidylinositol
      4,5-bisphosphate [PI(4,5)P2], a lipid controlling subsequent proinflammatory
      cytokine production. Here we show that stimulation of RAW264 macrophage-like
      cells with LPS induces global changes of the level of fatty-acylated, most likely
      palmitoylated, proteins. Among the acylated proteins that were up-regulated in
      those conditions were several enzymes of the phosphatidylinositol cycle. Global
      profiling of acylated proteins was performed by metabolic labeling of RAW264
      cells with 17ODYA, an analogue of palmitic acid functionalized with an alkyne
      group, followed by detection and enrichment of labeled proteins using biotin
      azide/streptavidin and their identification with mass spectrometry. This
      proteomic approach revealed that 154 fatty-acylated proteins were up-regulated,
      186 downregulated, and 306 not affected in cells stimulated with 100 ng/ml LPS
      for 60 min. The acylated proteins affected by LPS were involved in diverse
      biological functions, as found by Ingenuity Pathway Analysis. Detailed studies of
      17ODYA-labeled and immunoprecipitated proteins revealed that LPS induces S
      palmitoylation, hence activation, of type II phosphatidylinositol 4-kinase
      (PI4KII) beta, which phosphorylates phosphatidylinositol to phosphatidylinositol
      4-monophosphate, a PI(4,5)P2 precursor. Silencing of PI4KIIbeta and PI4KIIalpha
      inhibited LPS-induced expression and production of proinflammatory cytokines,
      especially in the TRIF-dependent signaling pathway of TLR4. Reciprocally, this
      LPS-induced signaling pathway was significantly enhanced after overexpression of
      PI4KIIbeta or PI4KIIalpha; this was dependent on palmitoylation of the kinases.
      However, the S-palmitoylation of PI4KIIalpha, hence its activity, was
      constitutive in RAW264 cells. Taken together the data indicate that LPS triggers
      S-palmitoylation and activation of PI4KIIbeta, which generates PI(4)P involved in
      signaling pathways controlling production of proinflammatory cytokines.

PMID- 29217622
TI  - Smoking paradox in the development of psoriatic arthritis among patients with
      psoriasis.

PMID- 29217623
TI  - Prostaglandins D2 and E2 have opposite effects on alveolar macrophages infected
      with Histoplasma capsulatum.
AB  - Prostaglandin E2 (PGE2) suppresses macrophage effector mechanisms; however,
      little is known about the function of PGD2 in infected alveolar macrophages
      (AMs). Using serum-opsonized Histoplasma capsulatum (Ops-H. capsulatum) in vitro,
      we demonstrated that AMs produced PGE2 and PGD2 in a time-dependent manner, with
      PGE2 levels exceeding those of PGD2 by 48 h postinfection. Comparison of the
      effects of both exogenous PGs on AMs revealed that PGD2 increased phagocytosis
      and killing through the chemoattractant receptor-homologous molecule expressed on
      Th2 lymphocytes receptor, whereas PGE2 had opposite effects, through E prostanoid
      (EP) receptor 2 (EP2)/EP4-dependent mechanisms. Moreover, PGD2 inhibited
      phospholipase C-gamma (PLC-gamma) phosphorylation, reduced IL-10 production, and
      increased leukotriene B4 receptor expression. In contrast, exogenous PGE2
      treatment reduced PLC-gamma phosphorylation, p38 and nuclear factor kappaB
      activation, TNF-alpha, H2O2, and leukotriene B4, but increased IL-1beta
      production. Using specific compounds to inhibit the synthesis of each PG in vitro
      and in vivo, we found that endogenous PGD2 contributed to fungicidal mechanisms
      and controlled inflammation, whereas endogenous PGE2 decreased phagocytosis and
      killing of the fungus and induced inflammation. These findings demonstrate that,
      although PGD2 acts as an immunostimulatory mediator to control H. capsulatum
      infection, PGE2 has immunosuppressive effects, and the balance between these two
      PGs may limit collateral immune damage at the expense of microbial containment.

PMID- 29217624
TI  - Applying a vernix caseosa based formulation accelerates skin barrier repair by
      modulating lipid biosynthesis.
AB  - Restoring the lipid homeostasis of the stratum corneum (SC) is a common strategy
      to enhance skin barrier function. Here, we used a ceramide containing vernix
      caseosa (VC)-based formulation and were able to accelerate barrier recovery in
      healthy volunteers. The recovery was examined over 16 days by monitoring trans
      epidermal water loss (TEWL) after barrier disruption by tape-stripping. Four skin
      sites were used to examine the effects of both treatment and barrier recovery.
      After 16 days, samples were harvested at these sites to examine the SC ceramide
      composition and lipid organization. Changes in ceramide profiles were identified
      using principal component analysis. After barrier recovery, the untreated sites
      showed increased levels of ceramide subclass AS and ceramides with a 34 total
      carbon-atom chain length, while the mean ceramide chain length was reduced. These
      changes were diminished by treatment with the studied formulation, which
      concurrently increased the formulated ceramides. Correlations were observed
      between SC lipid composition, lipid organization, and TEWL, and changes in the
      ceramide subclass composition suggest changes in the ceramide biosynthesis. These
      results suggest that VC-based formulations enhance skin barrier recovery and are
      attractive candidates to treat skin disorders with impaired barrier properties.

PMID- 29217626
TI  - Eating when ill is risky: immune defense impairs food detoxification in the
      caterpillar Manduca sexta.
AB  - Mounting an immune response consumes resources, which should lead to increased
      feeding. However, activating the immune system reduces feeding (i.e. illness
      induced anorexia) in both vertebrates and invertebrates, suggesting that it may
      be beneficial. We suggest that illness-induced anorexia may be an adaptive
      response to conflicts between immune defense and food detoxification. We found
      that activating an immune response in the caterpillar Manduca sexta increased its
      susceptibility to the toxin permethrin. Conversely, a sublethal dose of
      permethrin reduced resistance to the bacterium Serratia marcescens, demonstrating
      a negative interaction between detoxification and immune defense. Immune system
      activation and toxin challenge each depleted the amount of glutathione in the
      hemolymph. Increasing glutathione concentration in the hemolymph increased
      survival for both toxin- and immune+toxin-challenged groups. The results of this
      rescue experiment suggest that decreased glutathione availability, such as occurs
      during an immune response, impairs detoxification. We also found that the
      expression of some detoxification genes were not upregulated during a combined
      immune-toxin challenge, although they were when animals received a toxin
      challenge alone. These results suggest that immune defense reduces food
      detoxification capacity. Illness-induced anorexia may protect animals by
      decreasing exposure to food toxins when detoxification is impaired.

PMID- 29217625
TI  - Reducing gravity takes the bounce out of running.
AB  - In gravity below Earth-normal, a person should be able to take higher leaps in
      running. We asked 10 subjects to run on a treadmill in five levels of simulated
      reduced gravity and optically tracked centre-of-mass kinematics. Subjects
      consistently reduced ballistic height compared with running in normal gravity. We
      explain this trend by considering the vertical take-off velocity (defined as
      maximum vertical velocity). Energetically optimal gaits should balance the
      energetic costs of ground-contact collisions (favouring lower take-off velocity),
      and step frequency penalties such as leg swing work (favouring higher take-off
      velocity, but less so in reduced gravity). Measured vertical take-off velocity
      scaled with the square root of gravitational acceleration, following energetic
      optimality predictions and explaining why ballistic height decreases in lower
      gravity. The success of work-based costs in predicting this behaviour challenges
      the notion that gait adaptation in reduced gravity results from an unloading of
      the stance phase. Only the relationship between take-off velocity and swing cost
      changes in reduced gravity; the energetic cost of the down-to-up transition for a
      given vertical take-off velocity does not change with gravity. Because lower
      gravity allows an elongated swing phase for a given take-off velocity, the motor
      control system can relax the vertical momentum change in the stance phase, thus
      reducing ballistic height, without great energetic penalty to leg swing work.
      Although it may seem counterintuitive, using less 'bouncy' gaits in reduced
      gravity is a strategy to reduce energetic costs, to which humans seem extremely
      sensitive.

PMID- 29217627
TI  - The gastric caecum of larval Aedes aegypti: stimulation of epithelial ion
      transport by 5-hydroxytryptamine and cAMP.
AB  - We report measurements of ion transport across the gastric caecum of larvae of
      Aedes aegypti, a vector of yellow fever that inhabits a variety of aquatic
      habitats ranging from freshwater to brackish water. We provide the first
      measurements of the effect of 5-hydroxytryptamine (5-HT) on transepithelial
      potential (TEP), luminal ion concentrations and electrochemical potentials, as
      well as basolateral membrane potential and H+, Na+ and K+ fluxes. TEP,
      basolateral membrane potential, and H+, K+ and Na+ fluxes across the gastric
      caeca declined within 3-6 min after isolation of the entire midgut from the
      larva. 5-HT restored both the TEP and active accumulation of H+, K+ and Na+ in
      the lumen. Additionally, 5-HT restored H+, K+ and Na+ fluxes across the distal
      caecum of freshwater larvae, and restored H+ fluxes across the distal caecum of
      brackish water larvae. There was no effect of 5-HT on ion fluxes across the
      proximal caecum. We have also shown that 5-HT restores the basolateral membrane
      potential in cells of the distal, but not proximal, caecum. Effects of 5-HT on
      TEP and basolateral membrane potential were mimicked by application of cAMP but
      not by a phorbol ester. We provide a working model which proposes that 5-HT and
      cAMP stimulate the vacuolar H+-ATPase of the distal caecum. Our results provide
      evidence that the gastric caecum is functionally distinct from the adjacent
      anterior midgut and we discuss possible roles of the gastric caecum in
      osmoregulation. We also describe similarities in the arrangement of ion
      transporters in the caecum with those of the Malpighian tubules.

PMID- 29217628
TI  - Conversion efficiency of alpha-linolenic acid to omega-3 highly unsaturated fatty
      acids in aerial insectivore chicks.
AB  - Food availability and quality are both critical for growing young animals. In
      nature, swallows (Tachycineta bicolor) and other aerial insectivores feed on both
      aquatic insects, which are rich in omega-3 highly unsaturated fatty acids
      (HUFAs), and terrestrial insects, which contain considerably lower amounts of
      omega-3 HUFAs. Carnivorous mammals and fishes must obtain omega-3 HUFAs from
      their diet, as they have lost the capacity to convert the precursor omega-3 alpha
      linolenic acid (ALA) into omega-3 HUFAs. Thus, the relative value of aquatic
      versus terrestrial insects depends not only on the fatty acid composition of the
      prey but also on the capacity of consumers to convert ALA into omega-3 HUFAs. We
      used a combination of stable-isotope-labeled fatty acid tracers to ask whether,
      and how efficiently, tree swallows can deposit newly synthesized omega-3 HUFAs
      into tissue. Our data show for the first time that tree swallows can convert ALA
      into omega-3 HUFAs deposited in liver and skeletal muscle. However, high tree
      swallow demand for omega-3 HUFAs combined with low ALA availability in natural
      terrestrial foods may strain their modest conversion ability. This suggests that
      while tree swallows can synthesize omega-3 HUFAs de novo, omega-3 HUFAs are
      ecologically essential nutrients in natural systems. Our findings thus provide
      mechanistic support for our previous findings and the importance of omega-3 HUFA
      rich aquatic insects for tree swallows and most likely other aerial insectivores
      with similar niches.

PMID- 29217629
TI  - Map-like navigation from distances exceeding routine movements in the three
      striped poison frog (Ameerega trivittata).
AB  - Most animals move in dense habitats where distant landmarks are limited, but how
      they find their way around remains poorly understood. Poison frogs inhabit the
      rainforest understory, where they shuttle tadpoles from small territories to
      widespread pools. Recent studies revealed their excellent spatial memory and the
      ability to home back from several hundred meters. It remains unclear whether this
      homing ability is restricted to the areas that had been previously explored or
      whether it allows the frogs to navigate from areas outside their direct
      experience. Here, we used radio-tracking to study the navigational performance of
      three-striped poison frog translocated outside the area of their routine
      movements (200-800 m). Translocated frogs returned to their home territory via a
      direct path from all distances and with little difference in orientation
      accuracy, suggesting a flexible map-like navigation mechanism. These findings
      challenge our current understanding of both the mechanisms and the sensory basis
      of amphibian orientation.

PMID- 29217630
TI  - Woman in labour who was told not to come to hospital wins damages.

PMID- 29217631
TI  - How to deliver optimal cardiac resynchronisation therapy.

PMID- 29217632
TI  - Perioperative management of anticoagulant and antiplatelet therapy.

PMID- 29217633
TI  - Stress echocardiography in patients with native valvular heart disease.
AB  - Valve stress echocardiography (VSE) can be performed as exercise stress
      echocardiography (ESE) or dobutamine stress echocardiography (DSE) depending on
      the patient's clinical status, severity and type of valve disease. ESE combines
      exercise testing with two-dimensional grey scale and Doppler echocardiography
      during exercise. Thus, it provides objective assessment of symptomatic status
      (exercise test), as well as exercise-induced changes of a series of
      echocardiographic parameters (different depending on the valve disease type),
      which yield prognostic information in individual patients and help in a better
      treatment planning. DSE is useful in symptomatic patients with low-gradient
      aortic stenosis. It clarifies its severity and helps in assessing surgical risk
      in patients with severe disease and systolic dysfunction. It can be also used to
      test valve haemodynamics in asymptomatic patients with significant mitral
      stenosis unable to perform an exercise test or to test the left ventricle
      response, namely to test viability, in patients with ischaemic secondary mitral
      regurgitation. VSE has taught us that history taking, clinical examination and
      resting echocardiography give an 'incomplete picture' of the disease in patients
      presenting with a severe valve disease. Therefore, its use should be encouraged
      in such patients.

PMID- 29217634
TI  - Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention.
AB  - Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death
      leading to left ventricular dysfunction. Clinical heart failure may ensue in up
      to 5% of high-risk patients. Improved cancer survival together with better
      awareness of the late effects of cardiotoxicity has led to growing recognition of
      the need for surveillance of anthracycline-treated cancer survivors with early
      intervention to treat or prevent heart failure. The main mechanism of
      anthracycline cardiotoxicity is now thought to be through inhibition of
      topoisomerase 2beta resulting in activation of cell death pathways and inhibition
      of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age
      and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic
      susceptibility factors will help identify susceptible patients in the future.
      Cardiac imaging with echocardiographic measurement of global longitudinal strain
      and cardiac troponin detect early myocardial injury prior to the development of
      left ventricular dysfunction. There is no consensus on how best to monitor
      anthracycline cardiotoxicity although guidelines advocate quantification of left
      ventricular ejection fraction before and after chemotherapy with additional
      scanning being justified in high-risk patients. Patients developing significant
      left ventricular dysfunction with or without clinical heart failure should be
      treated according to established guidelines. Liposomal encapsulation reduces
      anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline
      interferes with binding to topoisomerase 2beta and reduces both cardiotoxicity
      and subsequent heart failure in high-risk patients. Angiotensin inhibition and
      beta-blockade are also protective and appear to prevent the development of left
      ventricular dysfunction when given prior or during chemotherapy in patients
      exhibiting early signs of cardiotoxicity.

PMID- 29217635
TI  - Early days in congenital heart surgery in the UK: the Peacock Club.

PMID- 29217636
TI  - Novel United Kingdom prognostic model for 30-day mortality following
      transcatheter aortic valve implantation.
AB  - OBJECTIVE: Existing clinical prediction models (CPM) for short-term mortality
      after transcatheter aortic valve implantation (TAVI) have limited applicability
      in the UK due to moderate predictive performance and inconsistent recording
      practices across registries. The aim of this study was to derive a UK-TAVI CPM to
      predict 30-day mortality risk for benchmarking purposes. METHODS: A two-step
      modelling strategy was undertaken: first, data from the UK-TAVI Registry between
      2009 and 2014 were used to develop a multivariable logistic regression CPM using
      backwards stepwise regression. Second, model-updating techniques were applied
      using the 2013-2014 data, thereby leveraging new approaches to include frailty
      and to ensure the model was reflective of contemporary practice. Internal
      validation was performed by bootstrapping to estimate in-sample optimism
      corrected performance. RESULTS: Between 2009 and 2014, up to 6339 patients were
      included across 34 centres in the UK-TAVI Registry (mean age, 81.3; 2927 female
      (46.2%)). The observed 30-day mortality rate was 5.14%. The final UK-TAVI CPM
      included 15 risk factors, which included two variables associated with frailty.
      After correction for in-sample optimism, the model was well calibrated, with a
      calibration intercept of 0.02 (95% CI -0.17 to 0.20) and calibration slope of
      0.79 (95% CI 0.55 to 1.03). The area under the receiver operating characteristic
      curve, after adjustment for in-sample optimism, was 0.66. CONCLUSION: The UK-TAVI
      CPM demonstrated strong calibration and moderate discrimination in UK-TAVI
      patients. This model shows potential for benchmarking, but even the inclusion of
      frailty did not overcome the need for more wide-ranging data and other outcomes
      might usefully be explored.

PMID- 29217638
TI  - Country-by-genotype-by-environment interaction in childhood academic achievement.

PMID- 29217637
TI  - How T cells grasp mycobacterial lipid antigens.

PMID- 29217639
TI  - Function of a retroviral envelope protein in the placenta of a viviparous lizard.

PMID- 29217640
TI  - Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell
      mechanotransduction.
AB  - Mechanoelectrical transduction in the inner ear is a biophysical process
      underlying the senses of hearing and balance. The key players involved in this
      process are mechanosensitive ion channels. They are located in the stereocilia of
      hair cells and opened by the tension in specialized molecular springs, the tip
      links, connecting adjacent stereocilia. When channels open, the tip links relax,
      reducing the hair-bundle stiffness. This gating compliance makes hair cells
      especially sensitive to small stimuli. The classical explanation for the gating
      compliance is that the conformational rearrangement of a single channel directly
      shortens the tip link. However, to reconcile theoretical models based on this
      mechanism with experimental data, an unrealistically large structural change of
      the channel is required. Experimental evidence indicates that each tip link is a
      dimeric molecule, associated on average with two channels at its lower end. It
      also indicates that the lipid bilayer modulates channel gating, although it is
      not clear how. Here, we design and analyze a model of mechanotransduction where
      each tip link attaches to two channels, mobile within the membrane. Their states
      and positions are coupled by membrane-mediated elastic forces arising from the
      interaction between the channels' hydrophobic cores and that of the lipid
      bilayer. This coupling induces cooperative opening and closing of the channels.
      The model reproduces the main properties of hair-cell mechanotransduction using
      only realistic parameters constrained by experimental evidence. This work
      provides an insight into the fundamental role that membrane-mediated ion-channel
      cooperativity can play in sensory physiology.

PMID- 29217641
TI  - Molecular chaperones maximize the native state yield on biological times by
      driving substrates out of equilibrium.
AB  - Molecular chaperones facilitate the folding of proteins and RNA in vivo. Under
      physiological conditions, the in vitro folding of Tetrahymena ribozyme by the RNA
      chaperone CYT-19 behaves paradoxically; increasing the chaperone concentration
      reduces the yield of native ribozymes. In contrast, the protein chaperone GroEL
      works as expected; the yield of the native substrate increases with chaperone
      concentration. The discrepant chaperone-assisted ribozyme folding thus
      contradicts the expectation that it operates as an efficient annealing machine.
      To resolve this paradox, we propose a minimal stochastic model based on the
      Iterative Annealing Mechanism (IAM) that offers a unified description of
      chaperone-mediated folding of both proteins and RNA. Our theory provides a
      general relation that quantitatively predicts how the yield of native states
      depends on chaperone concentration. Although the absolute yield of native states
      decreases in the Tetrahymena ribozyme, the product of the folding rate and the
      steady-state native yield increases in both cases. By using energy from ATP
      hydrolysis, both CYT-19 and GroEL drive their substrate concentrations far out of
      equilibrium, thus maximizing the native yield in a short time. This also holds
      when the substrate concentration exceeds that of GroEL. Our findings satisfy the
      expectation that proteins and RNA be folded by chaperones on biologically
      relevant time scales, even if the final yield is lower than what equilibrium
      thermodynamics would dictate. The theory predicts that the quantity of chaperones
      in vivo has evolved to optimize native state production of the folded states of
      RNA and proteins in a given time.

PMID- 29217643
TI  - Monitoring progress towards planetary health.

PMID- 29217644
TI  - Patient centred diagnosis of dementia: we must listen to patients' wishes.

PMID- 29217642
TI  - Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated
      Cardiomyopathy.
AB  - BACKGROUND: Myocardial metabolic impairment is a major feature in chronic heart
      failure. As the major coenzyme in fuel oxidation and oxidative phosphorylation
      and a substrate for enzymes signaling energy stress and oxidative stress
      response, nicotinamide adenine dinucleotide (NAD+) is emerging as a metabolic
      target in a number of diseases including heart failure. Little is known on the
      mechanisms regulating homeostasis of NAD+ in the failing heart. METHODS: To
      explore possible alterations of NAD+ homeostasis in the failing heart, we
      quantified the expression of NAD+ biosynthetic enzymes in the human failing heart
      and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by
      Serum Response Factor transcription factor depletion in the heart (SRFHKO) or of
      cardiac hypertrophy triggered by transverse aorta constriction. We studied the
      impact of NAD+ precursor supplementation on cardiac function in both mouse
      models. RESULTS: We observed a 30% loss in levels of NAD+ in the murine failing
      heart of both DCM and transverse aorta constriction mice that was accompanied by
      a decrease in expression of the nicotinamide phosphoribosyltransferase enzyme
      that recycles the nicotinamide precursor, whereas the nicotinamide riboside
      kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside precursor is
      increased, to a higher level in the DCM (40-fold) than in transverse aorta
      constriction (4-fold). This shift was also observed in human failing heart
      biopsies in comparison with nonfailing controls. We show that the Nmrk2 gene is
      an AMP-activated protein kinase and peroxisome proliferator-activated receptor
      alpha responsive gene that is activated by energy stress and NAD+ depletion in
      isolated rat cardiomyocytes. Nicotinamide riboside efficiently rescues NAD+
      synthesis in response to FK866-mediated inhibition of nicotinamide
      phosphoribosyltransferase and stimulates glycolysis in cardiomyocytes.
      Accordingly, we show that nicotinamide riboside supplementation in food
      attenuates the development of heart failure in mice, more robustly in DCM, and
      partially after transverse aorta constriction, by stabilizing myocardial NAD+
      levels in the failing heart. Nicotinamide riboside treatment also robustly
      increases the myocardial levels of 3 metabolites, nicotinic acid adenine
      dinucleotide, methylnicotinamide, and N1-methyl-4-pyridone-5-carboxamide, that
      can be used as validation biomarkers for the treatment. CONCLUSIONS: The data
      show that nicotinamide riboside, the most energy-efficient among NAD precursors,
      could be useful for treatment of heart failure, notably in the context of DCM, a
      disease with few therapeutic options.

PMID- 29217646
TI  - Risk tools are used to protect doctors and institutions.

PMID- 29217645
TI  - Do patients who die from an alcohol-related condition 'drift' into areas of
      greater deprivation? Alcohol-related mortality and health selection theory in
      Scotland.
AB  - BACKGROUND: Health selection has been proposed to explain the patterning of
      alcohol-related mortality by area deprivation. This study investigated whether
      persons who die from alcohol-related conditions are more likely to experience
      social drift than those who die from other causes. METHODS: Deaths recorded in
      Scotland (2013, >21 years) were coded as 'alcohol-related' or 'other' and by
      deprivation decile of residence at death. Acute hospital admissions data from
      1996 to 2012 were used to provide premortality deprivation data. chi2 tests
      estimated the difference between observed and expected alcohol-related deaths by
      first Scottish Index of Multiple Deprivation (SIMD) decile and type of death.
      Logistic regression models were fitted using type of death as the outcome of
      interest and change in SIMD decile as the exposure of interest. RESULTS: Of 47
      012 deaths, 1458 were alcohol-related. Upward and downward mobility was observed
      for both types of death. An estimated 31 more deaths than expected were
      classified 'alcohol-related' among cases whose deprivation score decreased, while
      204 more deaths than expected were classified 'alcohol-related' among cases whose
      initial deprivation ranking was in the four most deprived deciles. Becoming more
      deprived and first deprivation category were both associated with increased odds
      of type of death being alcohol-related after adjusting for confounders.
      CONCLUSION: This study suggests that health selection appears to contribute less
      to the deprivation gradient in alcohol-related mortality in Scotland than an
      individual's initial area deprivation category.

PMID- 29217647
TI  - Things that go BONG! in the night.

PMID- 29217648
TI  - The interaction of ENL with PAF1 mitigates polycomb silencing and facilitates
      murine leukemogenesis.
AB  - Eleven-nineteen leukemia (ENL) is a chromatin reader present in complexes
      stimulating transcriptional elongation. It is fused to mixed-lineage leukemia
      (MLL) in leukemia, and missense mutations have been identified in Wilms tumor and
      acute myeloid leukemia. Here we demonstrate that ENL overcomes polycomb silencing
      through recruitment of PAF1 via the conserved YEATS domain, which recognizes
      acetylated histone H3. PAF1 was responsible for antirepressive activities of ENL
      in vitro, and it determined the transforming potential of MLL-ENL. MLL-ENL target
      loci showed supraphysiological PAF1 binding, hyperubiquitination of histone H2B
      and hypomodification with H2AUb, resulting in accelerated transcription rates.
      YEATS mutations induced a gain of function, transforming primary hematopoietic
      cells in vitro and in transplantation assays through aberrant transcription and
      H2B ubiquitination of Hoxa9 and Meis1 Mechanistically, H3 and PAF1 competed for
      ENL interaction, with activating mutations favoring PAF1 binding, whereas the MLL
      moiety provided a constitutive PAF1 tether allowing MLL fusions to circumvent H3
      competition.

PMID- 29217649
TI  - An unusual cause of hypoxia: getting to the heart of the matter.
AB  - A 63 year old female presented to hospital with progressive exertional dyspnoea
      over a 6 month period. In the year preceding her admission, she reported an
      intercurrent history of abdominal pain, diarrhoea and weight loss. She was found
      to be hypoxic, the cause for which was initially unclear. A ventilation-perfusion
      scan identified a right-to-left shunt. Transoesophageal echocardiography (TOE)
      demonstrated a significant right-to-left intracardiac shunt through a patent
      foramen ovale (PFO); additionally severe tricuspid regurgitation was noted
      through a highly abnormal tricuspid valve. The findings were consistent with
      carcinoid heart disease with a haemodynamically significant shunt, resulting in
      profound systemic hypoxia. 24 hour urinary 5-Hydroxyindoleacetic acid (5-HIAA)
      and imaging were consistent with a terminal ileal primary carcinoid cancer with
      hepatic metastasis. Liver biopsy confirmed a tissue diagnosis. The patient was
      commenced on medical therapy for carcinoid syndrome. She subsequently passed away
      while undergoing anaesthetic induction for valvular surgery to treat her
      carcinoid heart disease and PFO.

PMID- 29217650
TI  - Serum and urine vitamin D metabolite analysis in early preeclampsia.
AB  - Vitamin D deficiency is common in pregnant women and may contribute to adverse
      events in pregnancy such as preeclampsia (PET). To date, studies of vitamin D and
      PET have focused primarily on serum concentrations vitamin D, 25-hydroxyvitamin
      D3 (25(OH)D3) later in pregnancy. The aim here was to determine whether a more
      comprehensive analysis of vitamin D metabolites earlier in pregnancy could
      provide predictors of PET. Using samples from the SCOPE pregnancy cohort,
      multiple vitamin D metabolites were quantified by liquid chromatography-tandem
      mass spectrometry in paired serum and urine prior to the onset of PET symptoms.
      Samples from 50 women at pregnancy week 15 were analysed, with 25 (50%)
      developing PET by the end of the pregnancy and 25 continuing with uncomplicated
      pregnancy. Paired serum and urine from non-pregnant women (n = 9) of reproductive
      age were also used as a control. Serum concentrations of 25(OH)D3, 25(OH)D2,
      1,25(OH)2D3, 24,25(OH)2D3 and 3-epi-25(OH)D3 were measured and showed no
      significant difference between women with uncomplicated pregnancies and those
      developing PET. As previously reported, serum 1,25(OH)2D3 was higher in all
      pregnant women (in the second trimester), but serum 25(OH)D2 was also higher
      compared to non-pregnant women. In urine, 25(OH)D3 and 24,25(OH)2D3 were
      quantifiable, with both metabolites demonstrating significantly lower (P < 0.05)
      concentrations of both of these metabolites in those destined to develop PET.
      These data indicate that analysis of urinary metabolites provides an additional
      insight into vitamin D and the kidney, with lower urinary 25(OH)D3 and
      24,25(OH)2D3 excretion being an early indicator of a predisposition towards
      developing PET.

PMID- 29217651
TI  - Interleukin-18 serum level is elevated in type 2 diabetes and latent autoimmune
      diabetes.
AB  - BACKGROUND: Interleukin-18 (IL-18) is an inflammatory cytokine found to be
      elevated in obesity, metabolic syndrome and type 2 diabetes (T2D) as a part of
      the chronic low-grade inflammatory process in these states. The aim of the study
      was to evaluate the interleukin level in patients with latent autoimmune diabetes
      of the adults (LADA) in comparison to that in T2D subjects. MATERIALS AND
      METHODS: IL-18 was analyzed through enzyme-linked immunosorbent assay in 76
      participants with T2D and 24 with LADA and 14 control subjects. Evaluation was
      also carried out in body mass index (BMI)- and glycemic control-matched diabetic
      patients. RESULTS: The serum concentration of IL-18 was higher in patients with
      T2D (389.04 +/- 203.44 pg/mL) and LADA (327.04 +/- 144.48 pg/mL) than that in
      control subjects (219.88 +/- 91.03 pg/mL), P < 0.05. However, it was not
      significantly different between both diabetic groups (P = 0.255) despite higher
      IL-6 (4.78 +/- 5.84 vs 1.79 +/- 0.96 pg/mL, P < 0.001) and hs-CRP (2.60 +/- 1.70
      vs 1.29 +/- 1.20 mg/L, P = 0.002) level in T2D patients. The results were
      persistent in BMI-matched subjects with diabetes (IL-18 = 403.48 +/- 226.32 vs
      329.30 +/- 146.30 pg/mL, respectively for T2D and LADA, P = 0.391). The
      correlations in T2D group concerning HDL cholesterol (r = -0.377, P = 0.001),
      postprandial glucose (r = 0.244, P = 0.043), IL-6 (r = 0.398, P < 0.001) and hs
      CRP (r = 0.427, P = 0.001) were not confirmed in LADA and control subjects.
      CONCLUSION: The IL-18 serum level was higher in T2D and LADA than that in control
      subjects, but did not differ between both diabetic groups, even when they were
      BMI matched. Correlations with lipid, glycemic and inflammatory parameters were
      present in T2D only.

PMID- 29217652
TI  - Initial clinical presentation and spectrum of pheochromocytoma: a study of 94
      cases from a single center.
AB  - BACKGROUND: With the increasing access to imaging more pheochromocytomas are
      diagnosed in the workup of adrenal incidentalomas. This may have changed the
      occurrence of the classic presentation with hypertension and the classic triad
      (headaches, sweating and palpitation). METHODS: We reviewed 94 consecutive cases
      of pheochromocytomas. Two cases of ectopic ACTH-syndrome were subsequently
      excluded. RESULTS: Of the 92 cases included 64% had presented as an
      incidentaloma, 32% as a suspected pheochromocytoma and 4% had been screened
      because of previously diagnosed MEN2A. Those screened were youngest while those
      with incidentalomas were oldest. The females were more common in the
      incidentaloma and the screening groups, and males in the suspected
      pheochromocytoma group. Measurements of noradrenaline/normetanephrine levels were
      highest in the suspected pheocromocytoma group and lowest in the screening group.
      Hypertension was present in 63% of the incidentalomas, 79% of suspected
      pheochromocytomas and in none of the screening group. Paroxysmal symptoms were
      present in almost all with suspected pheochromocytoma while only in half of the
      other groups. The suspected pheocromocytoma group had most symptoms and the
      screening group least. The classic triad was present in 14% of the
      incidentalomas, in 28% of the suspected and in none of the screening group, while
      no symptoms at all was present in 12%, 0% and 25%, respectively. Pheochromocytoma
      crisis occurred in 5%. There was a positive correlation between tumor size vs
      hormone levels, and catecholamine levels vs blood pressure. CONCLUSION:
      Clinicians need to be aware of the modern presentation of pheochromocytomas since
      early identification can be life-saving.

PMID- 29217653
TI  - Exenatide treatment causes suppression of serum fasting ghrelin levels in
      patients with type 2 diabetes mellitus.
AB  - AIM: In the present study, we investigated the long-term effects of exenatide
      treatment on serum fasting ghrelin levels in patients with type 2 diabetes
      mellitus. METHODS: Type 2 diabetic patients, who were using metformin with and
      without the other antihyperglycemic drugs on a stable dose for at least 3 months,
      were enrolled in the study. BMI>35 kg/m2 and HbA1c>7.0% were the additional
      inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were
      stopped, and metformin treatment was continued at 2000 mg per day. Exenatide
      treatment was initiated at 5 ug per dose subcutaneously (sc) twice daily, and
      after one month, the dose of exenatide was increased to 10 ug twice daily.
      Changes in anthropometric variables, glycemic control, lipid parameters and total
      ghrelin levels were evaluated at baseline and following 12 weeks of treatment.
      RESULTS: Thirty-eight patients (male/female = 7/31) entered the study. The mean
      age of patients was 50.5 +/- 8.8 years with a mean diabetes duration of 8.5 +/-
      4.9 years. The mean BMI was 41.6 +/- 6.3 kg/m2 and the mean HbA1c of patients was
      8.9 +/- 1.4%. The mean change in the weight of patients was -5.6 kg and the
      percentage change in weight was -5.2 +/- 3.7% following 12 weeks of treatment.
      BMI, fasting plasma glucose and HbA1c levels of patients were decreased
      significantly (P < 0.001 and P < 0.001; respectively), while there was no change
      in lipid parameters. Serum fasting ghrelin levels were significantly suppressed
      following 12 weeks of exenatide treatment compared with baseline values (328.4 +/
      166.8 vs 245.3 +/- 164.8 pg/mL) (P = 0.024). CONCLUSION: These results suggest
      that the effects of exenatide on weight loss may be related with the suppression
      of serum fasting ghrelin levels, which is an orexigenic peptide.

PMID- 29217654
TI  - The p300 and CBP Transcriptional Coactivators Are Required for beta-Cell and
      alpha-Cell Proliferation.
AB  - p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone
      acetyltransferase activity. Various beta-cell transcription factors can recruit
      p300/CBP, and thus the coactivators could be important for beta-cell function and
      health in vivo. We hypothesized that p300/CBP contribute to the development and
      proper function of pancreatic islets. To test this, we bred and studied mice
      lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets
      developed glucose intolerance attributable to impaired insulin secretion,
      together with reduced alpha- and beta-cell area and islet insulin content. These
      phenotypes were exacerbated in mice with only a single copy of p300 or CBP
      expressed in islets. Removing p300 in pancreatic endocrine progenitors impaired
      proliferation of neonatal alpha- and beta-cells. Mice lacking all four copies of
      p300/CBP in pancreatic endocrine progenitors failed to establish alpha- and beta
      cell mass postnatally. Transcriptomic analyses revealed significant overlaps
      between p300/CBP-downregulated genes and genes downregulated in Hnf1alpha-null
      islets and Nkx2.2-null islets, among others. Furthermore, p300/CBP are important
      for the acetylation of H3K27 at loci downregulated in Hnf1alpha-null islets. We
      conclude that p300 and CBP are limiting cofactors for islet development, and
      hence for postnatal glucose homeostasis, with some functional redundancy.

PMID- 29217655
TI  - Regulation of Lipolytic Response and Energy Balance by Melanocortin 2 Receptor
      Accessory Protein (MRAP) in Adipocytes.
AB  - Melanocortin 2 receptor accessory protein (MRAP) is highly expressed in adrenal
      gland and adipose tissue. In adrenal cells, MRAP is essential for
      adrenocorticotropic hormone (ACTH)-induced activation of the cAMP/protein kinase
      A (PKA) pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid
      production and secretion. Although ACTH was known to stimulate PKA-dependent
      lipolysis, the functional involvement of MRAP in adipocyte metabolism remains
      incompletely defined. Herein, we found that knockdown or overexpression of MRAP
      in 3T3-L1 adipocytes reduced or increased ACTH-induced lipolysis, respectively.
      Moreover, an unbiased proteomics screen and coimmunoprecipitation analysis
      identified Galphas as a novel interacting partner of MRAP. An MRAP mutant
      disabled in Galphas association failed to augment the activation of PKA and
      lipolytic response to ACTH. Furthermore, compared with wild-type mice, transgenic
      mice (aP2-MRAP) overexpressing MRAP fat specifically exhibited increased
      lipolytic response to ACTH. When fed a high-fat diet (HFD), the transgenic mice
      displayed a significant decrease in the gain of adiposity and body weight as well
      as an improvement in glucose and insulin tolerance. These phenotypes were
      accompanied by increased adipose expression of genes for mitochondrial fatty acid
      oxidation and thermogenesis, and overall energy expenditure. Collectively, our
      data strongly suggest that MRAP plays a critical role in the regulation of ACTH
      induced adipose lipolysis and whole-body energy balance.

PMID- 29217656
TI  - Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological
      Mechanisms and Relevance to Pharmacology.
AB  - Classically, polyunsaturated fatty acids (PUFA) were largely thought to be
      relatively inert structural components of brain, largely important for the
      formation of cellular membranes. Over the past 10 years, a host of bioactive
      lipid mediators that are enzymatically derived from arachidonic acid, the main n
      6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to
      regulate peripheral immune function, have been detected in the brain and shown to
      regulate microglia activation. Recent advances have focused on how PUFA regulate
      the molecular signaling of microglia, especially in the context of
      neuroinflammation and behavior. Several active drugs regulate brain lipid
      signaling and provide proof of concept for targeting the brain. Because brain
      lipid metabolism relies on a complex integration of diet, peripheral metabolism,
      including the liver and blood, which supply the brain with PUFAs that can be
      altered by genetics, sex, and aging, there are many pathways that can be
      disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling
      pathways are altered in neurologic disorders and may be viable targets for the
      development of novel therapeutics. In this study, we discuss in particular how n
      3 PUFAs and their metabolites regulate microglia phenotype and function to exert
      their anti-inflammatory and proresolving activities in the brain.

PMID- 29217658
TI  - Nucleic acid-based nanotechnology: The ability of DNA and RNA to fold into
      precise and complex shapes can be exploited for applications both in biology and
      electronics.

PMID- 29217657
TI  - The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the
      permeability transition pore by acidic pH.
AB  - The permeability transition pore (PTP) is a Ca2+-dependent mitochondrial channel
      whose opening causes a permeability increase in the inner membrane to ions and
      solutes. The most potent inhibitors are matrix protons, with channel block at pH
      6.5. Inhibition is reversible, mediated by histidyl residue(s), and prevented by
      their carbethoxylation by diethylpyrocarbonate (DPC), but their assignment is
      unsolved. We show that PTP inhibition by H+ is mediated by the highly conserved
      histidyl residue (H112 in the human mature protein) of oligomycin sensitivity
      conferral protein (OSCP) subunit of mitochondrial F1FO (F)-ATP synthase, which we
      also show to undergo carbethoxylation after reaction of mitochondria with DPC.
      Mitochondrial PTP-dependent swelling cannot be inhibited by acidic pH in H112Q
      and H112Y OSCP mutants, and the corresponding megachannels (the
      electrophysiological counterpart of the PTP) are insensitive to inhibition by
      acidic pH in patch-clamp recordings of mitoplasts. Cells harboring the H112Q and
      H112Y mutations are sensitized to anoxic cell death at acidic pH. These results
      demonstrate that PTP channel formation and its inhibition by H+ are mediated by
      the F-ATP synthase.

PMID- 29217659
TI  - ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and
      squamous cell carcinoma proliferation.
AB  - p63, more specifically its DeltaNp63alpha isoform, plays essential roles in
      squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear
      transport remain unknown. Nucleoporins (NUPs) are a family of proteins building
      nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear
      envelope. Recent evidence suggests a cell type-specific function for certain
      NUPs; however, the significance of NUPs in SCC biology remains unknown. In this
      study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified
      squamous epithelia and is further elevated in SCCs. Depletion of NUP62 inhibits
      proliferation and augments differentiation of SCC cells. The impaired ability to
      maintain the undifferentiated status is associated with defects in DeltaNp63alpha
      nuclear transport. We further find that differentiation-inducible Rho kinase
      reduces the interaction between NUP62 and DeltaNp63alpha by phosphorylation of
      phenylalanine-glycine regions of NUP62, attenuating DeltaNp63alpha nuclear
      import. Our results characterize NUP62 as a gatekeeper for DeltaNp63alpha and
      uncover its role in the control of cell fate through regulation of DeltaNp63alpha
      nuclear transport in SCC.

PMID- 29217660
TI  - Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing
      antibody responses.
AB  - Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two
      members of the Pneumoviridae family, account for the majority of severe lower
      respiratory tract infections worldwide in very young children. They are also a
      frequent cause of morbidity and mortality in the elderly and immunocompromised
      adults. High levels of neutralizing antibodies, mostly directed against the viral
      fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV
      However, no cross-neutralization is observed in polyclonal antibody responses
      raised after virus infection or immunization with purified F proteins. Based on
      crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which
      certain residues of well-characterized antigenic sites were swapped between the
      two antigens. The antigenic changes were monitored by ELISA with virus-specific
      monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal
      cross-neutralizing antibody responses, and mice were protected against challenge
      with the virus used for grafting of the heterologous antigenic site. These
      results provide a proof of principle for chimeric fusion proteins as single
      immunogens that can induce cross-neutralizing antibody and protective responses
      against more than one human pneumovirus.

PMID- 29217661
TI  - FoxO3 an important player in fibrogenesis and therapeutic target for idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal parenchymal lung
      disease with limited therapeutic options, with fibroblast-to-myofibroblast
      transdifferentiation and hyperproliferation playing a major role. Investigating
      ex vivo-cultured (myo)fibroblasts from human IPF lungs as well as fibroblasts
      isolated from bleomycin-challenged mice, Forkhead box O3 (FoxO3) transcription
      factor was found to be less expressed, hyperphosphorylated, and nuclear-excluded
      relative to non-diseased controls. Downregulation and/or hyperphosphorylation of
      FoxO3 was reproduced by exposure of normal human lung fibroblasts to various pro
      fibrotic growth factors and cytokines (FCS, PDGF, IGF1, TGF-beta1). Moreover,
      selective knockdown of FoxO3 in the normal human lung fibroblasts reproduced the
      transdifferentiation and hyperproliferation phenotype. Importantly, mice with
      global- (Foxo3-/-) or fibroblast-specific (Foxo3f.b-/-) FoxO3 knockout displayed
      enhanced susceptibility to bleomycin challenge, with augmented fibrosis, loss of
      lung function, and increased mortality. Activation of FoxO3 with UCN-01, a
      staurosporine derivative currently investigated in clinical cancer trials,
      reverted the IPF myofibroblast phenotype in vitro and blocked the bleomycin
      induced lung fibrosis in vivo These studies implicate FoxO3 as a critical
      integrator of pro-fibrotic signaling in lung fibrosis and pharmacological
      reconstitution of FoxO3 as a novel treatment strategy.

PMID- 29217662
TI  - Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients
      With Ischemic Stroke.
AB  - BACKGROUND: This study was performed to determine the clinical correlates and
      long-term prognostic implications of microbleed burden and location in Chinese
      patients with ischemic stroke. METHODS AND RESULTS: We recruited 1003
      predominantly Chinese patients with ischemic stroke who received magnetic
      resonance imaging at the University of Hong Kong. We determined the clinical
      correlates of microbleeds and the long-term risks (3126 patient-years of follow
      up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed
      burden (0 versus 1, 2-4, and >=5) and location, adjusting for age, sex, and
      vascular risk factors and stratified by antithrombotic use. Microbleeds were
      present in 450 of 1003 of the study population (119/450 had >=5, 187/450 had
      mixed location). Having >=5 microbleeds was independently associated with prior
      antiplatelet and anticoagulant use, whereas microbleeds of mixed location were
      independently associated with hypertension and prior anticoagulant use (all
      P<0.05). Microbleed burden was associated with an increased risk of ICH
      (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard
      ratio: 0.59 [95% confidence interval, 0.07-5.05]; 2-4 microbleeds: multivariate
      hazard ratio: 2.14 [95% confidence interval, 0.50-9.12]; >=5 microbleeds:
      multivariate hazard ratio: 9.51 [95% confidence interval, 3.25-27.81];
      Ptrend<0.0001), but the relationship of microbleed burden and risk of recurrent
      ischemic stroke was not significant (Ptrend=0.054). Similar findings were noted
      in the 862 of 1003 patients treated with antiplatelet agents only (ICH:
      Ptrend<0.0001; ischemic stroke Ptrend=0.096). Multivariate analysis revealed
      that, independent of vascular risk factors, antithrombotic use, and other
      neuroimaging markers of small vessel disease, having >=5 microbleeds
      (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11-33.21]; P=0.037)
      was identified as an independent predictor of subsequent ICH, but neither
      microbleed burden nor location was predictive of recurrent ischemic stroke risk.
      CONCLUSIONS: In Chinese patients with ischemic stroke, a high burden of cerebral
      microbleeds was significantly associated with an increased risk of ICH; however,
      neither microbleed location nor burden was associated with recurrent ischemic
      stroke risk.

PMID- 29217663
TI  - Prevalence and Clinical Characteristics of Refractory Hypertension.
AB  - BACKGROUND: We aimed to estimate the prevalence of refractory hypertension (RfH)
      and to determine the clinical differences between these patients and resistant
      hypertensives (RH). Secondly, we assessed the prevalence of white-coat RfH and
      clinical differences between true- and white-coat RfH patients. METHODS AND
      RESULTS: The present analysis was conducted on the Spanish Ambulatory Blood
      Pressure Monitoring Registry database containing 70 997 treated hypertensive
      patients. RH and RfH were defined by the presence of elevated office blood
      pressure (>=140 and/or 90 mm Hg) in patients treated with at least 3 (RH) and 5
      (RfH) antihypertensive drugs. White-coat RfH was defined by RfH with normal
      (<130/80 mm Hg) 24-hour blood pressure. A total of 11.972 (16.9%) patients
      fulfilled the standard criteria of RH, and 955 (1.4%) were considered as having
      RfH. Compared with RH patients, those with RfH were younger, more frequently
      male, and after adjusting for age and sex, had increased prevalence of target
      organ damage, and previous cardiovascular disease. The prevalence of white coat
      RfH was lower than white-coat RH (26.7% versus 37.1%, P<0.001). White-coat RfH,
      in comparison with those with true RfH, showed a lower prevalence of both left
      ventricular hypertrophy (22% versus 29.7%; P=0.018) and microalbuminuria (28.3%
      versus 42.9%; P=0.047). CONCLUSIONS: The prevalence of RfH was low and these
      patients had a greater cardiovascular risk profile compared with RH. One out of 4
      patients with RfH have normal 24-hour blood pressure and less target organ
      damage, thus indicating the important role of ambulatory blood pressure
      monitoring in guiding antihypertensive therapy in difficult-to-treat patients.

PMID- 29217665
TI  - Critical determinants of combined sprint and endurance performance: an
      integrative analysis from muscle fiber to the human body.
AB  - Optimizing physical performance is a major goal in current physiology. However,
      basic understanding of combining high sprint and endurance performance is
      currently lacking. This study identifies critical determinants of combined sprint
      and endurance performance using multiple regression analyses of physiologic
      determinants at different biologic levels. Cyclists, including 6 international
      sprint, 8 team pursuit, and 14 road cyclists, completed a Wingate test and 15-km
      time trial to obtain sprint and endurance performance results, respectively.
      Performance was normalized to lean body mass2/3 to eliminate the influence of
      body size. Performance determinants were obtained from whole-body oxygen
      consumption, blood sampling, knee-extensor maximal force, muscle oxygenation,
      whole-muscle morphology, and muscle fiber histochemistry of musculus vastus
      lateralis. Normalized sprint performance was explained by percentage of fast-type
      fibers and muscle volume ( R2 = 0.65; P < 0.001) and normalized endurance
      performance by performance oxygen consumption ( Vo2), mean corpuscular hemoglobin
      concentration, and muscle oxygenation ( R2 = 0.92; P < 0.001). Combined sprint
      and endurance performance was explained by gross efficiency, performance Vo2, and
      likely by muscle volume and fascicle length ( P = 0.056; P = 0.059). High
      performance Vo2 related to a high oxidative capacity, high capillarization *
      myoglobin, and small physiologic cross-sectional area ( R2 = 0.67; P < 0.001).
      Results suggest that fascicle length and capillarization are important targets
      for training to optimize sprint and endurance performance simultaneously.-Van der
      Zwaard, S., van der Laarse, W. J., Weide, G., Bloemers, F. W., Hofmijster, M. J.,
      Levels, K., Noordhof, D. A., de Koning, J. J., de Ruiter, C. J., Jaspers, R. T.
      Critical determinants of combined sprint and endurance performance: an
      integrative analysis from muscle fiber to the human body.

PMID- 29217666
TI  - EPAC1 regulates endothelial annexin A2 cell surface translocation and plasminogen
      activation.
AB  - Annexins, a family of highly conserved calcium- and phospholipid-binding
      proteins, play important roles in a wide range of physiologic functions. Among
      the 12 known annexins in humans, annexin A2 (AnxA2) is one of the most
      extensively studied and has been implicated in various human diseases. AnxA2 can
      exist as a monomer or a heterotetrameric complex with S100A10 (P11) and plays a
      critical role in many cellular processes, including exocytosis, endocytosis, and
      membrane organization. At the endothelial cell surface, the (AnxA2?P11)2 tetramer
      acting as a coreceptor for plasminogen and tissue plasminogen activator (tPA)
      accelerates tPA-dependent activation of the fibrinolytic protease, plasmin, the
      enzyme that is responsible for thrombus dissolution and the degradation of
      fibrin. This study demonstrates that EPAC1 (exchange proteins directly activated
      by cAMP isoform 1) interacts with AnxA2 and regulates its biologic functions by
      modulating its membrane translocation in endothelial cells. By using genetic and
      pharmacologic approaches, we demonstrate that EPAC1-acting via the PLCepsilon-PKC
      pathway-inhibits AnxA2 surface translocation and plasminogen activation. These
      results suggest that EPAC1 plays a role in the regulation of fibrinolysis in
      endothelial cells and may represent a novel therapeutic target for disorders of
      fibrinolysis.-Yang, W., Mei, F. C., Cheng, X. EPAC1 regulates endothelial annexin
      A2 cell surface translocation and plasminogen activation.

PMID- 29217667
TI  - Critical contribution of Na+-Ca2+ exchanger to the Ca2+-mediated vasodilation
      activated in endothelial cells of resistance arteries.
AB  - Na+-Ca2+ exchanger (NCX) contributes to control the intracellular free Ca2+
      concentration ([Ca2+]i), but the functional activation of NCX reverse mode
      (NCXrm) in endothelial cells is controversial. We evaluated the participation of
      NCXrm-mediated Ca2+ uptake in the endothelium-dependent vasodilation of rat
      isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the
      acetylcholine (ACh)-induced vasodilation was abolished by treatment with the
      NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced
      hyperpolarization observed in primary cultures of mesenteric endothelial cells
      and in smooth muscle of isolated mesenteric resistance arteries was attenuated by
      KB-R7943 and SEA0400, respectively. In addition, both blockers abolished the NO
      production activated by ACh in intact mesenteric arteries. In contrast, the
      inhibition of NCXrm did not affect the vasodilator responses induced by the Ca2+
      ionophore, ionomycin, and the NO donor, S-nitroso- N-acetylpenicillamine.
      Furthermore, SEA0400, KB-R7943, and a small interference RNA directed against
      NCX1 blunted the increase in [Ca2+]i induced by ACh or ATP in cultured
      endothelial cells. The analysis by proximity ligation assay showed that the NO
      synthesizing enzyme, eNOS, and NCX1 were associated in endothelial cell caveolae
      of intact mesenteric resistance arteries. These results indicate that the
      activation of NCXrm has a central role in Ca2+-mediated vasodilation initiated by
      ACh in endothelial cells of resistance arteries.-Lillo, M. A., Gaete, P. S.,
      Puebla, M., Ardiles, N. M., Poblete, I., Becerra, A., Simon, F., Figueroa, X. F.
      Critical contribution of Na+-Ca2+ exchanger to the Ca2+-mediated vasodilation
      activated in endothelial cells of resistance arteries.

PMID- 29217668
TI  - Induced global deletion of glucocorticoid receptor impairs fracture healing.
AB  - Although endogenous glucocorticoids (GCs) are important regulators of bone
      integrity and the immune system, their role in bone repair after fracture-a
      process highly dependent on inflammation and bone formation-is unclear. Because
      most effects of GCs are mediated by the glucocorticoid receptor (GR), we used an
      inducible global GR knockout (GRgtROSACreERT2) mouse model to eliminate
      endogenous GC action in all cells contributing to bone repair. The healing
      process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry,
      histology, gene-expression analysis, microcomputed tomography, and biomechanical
      analysis. We observed increased early systemic and local inflammatory responses,
      as well as a significantly higher number of T cells infiltrating the fracture
      callus. Later in the healing process, we found impaired endochondral ossification
      in the absence of the GR, leading to persistent cartilage in the calli of the
      GRgtROSACreERT2 mice, decreased bending stiffness, and a significantly lower
      proportion of healed bones. Collectively, our data show that the absence of the
      GR significantly impairs fracture healing associated with a defective cartilage
      to-bone transition, underscoring an important role of GCs during fracture
      healing.-Rapp, A. E., Hachemi, Y., Kemmler, J., Koenen, M., Tuckermann, J.,
      Ignatius, A. Induced global deletion of glucocorticoid receptor impairs fracture
      healing.

PMID- 29217664
TI  - Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer
      Therapies: A Systematic Review.
AB  - BACKGROUND: The cardiovascular complications of cancer therapeutics are the focus
      of the burgeoning field of cardio-oncology. A common challenge in this field is
      the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and
      the potential risk for the life-threatening arrhythmia torsades de pointes.
      Although QT prolongation is not a perfect marker of arrhythmia risk, this has
      become a primary safety metric among oncologists. Cardiologists caring for
      patients receiving cancer treatment should become familiar with the drugs
      associated with QT prolongation, its incidence, and appropriate management
      strategies to provide meaningful consultation in this complex clinical scenario.
      METHODS AND RESULTS: In this article, we performed a systematic review (using
      Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines) of commonly used cancer drugs to determine the incidence of QT
      prolongation and clinically relevant arrhythmias. We calculated summary estimates
      of the incidence of all and clinically relevant QT prolongation as well as
      arrhythmias and sudden cardiac death. We then describe strategies to prevent,
      identify, and manage QT prolongation in patients receiving cancer therapy. We
      identified a total of 173 relevant publications. The weighted incidence of any
      corrected QT (QTc) prolongation in our systematic review in patients treated with
      conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc
      >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc
      prolongation with targeted therapies (eg, small molecular tyrosine kinase
      inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms)
      reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were
      rare. CONCLUSIONS: Our systematic review demonstrates that there is variability
      in the incidence of QTc prolongation of various cancer drugs; however, the
      clinical consequence, as defined by arrhythmias or sudden cardiac death, remains
      rare.

PMID- 29217669
TI  - Maternal choline supplementation during the third trimester of pregnancy improves
      infant information processing speed: a randomized, double-blind, controlled
      feeding study.
AB  - Rodent studies demonstrate that supplementing the maternal diet with choline
      during pregnancy produces life-long cognitive benefits for the offspring. In
      contrast, the two experimental studies examining cognitive effects of maternal
      choline supplementation in humans produced inconsistent results, perhaps because
      of poor participant adherence and/or uncontrolled variation in intake of choline
      or other nutrients. We examined the effects of maternal choline supplementation
      during pregnancy on infant cognition, with intake of choline and other nutrients
      tightly controlled. Women entering their third trimester were randomized to
      consume, until delivery, either 480 mg choline/d ( n = 13) or 930 mg choline/d (
      n = 13). Infant information processing speed and visuospatial memory were tested
      at 4, 7, 10, and 13 mo of age ( n = 24). Mean reaction time averaged across the
      four ages was significantly faster for infants born to mothers in the 930 ( vs.
      480) mg choline/d group. This result indicates that maternal consumption of
      approximately twice the recommended amount of choline during the last trimester
      improves infant information processing speed. Furthermore, for the 480-mg
      choline/d group, there was a significant linear effect of exposure duration
      (infants exposed longer showed faster reaction times), suggesting that even
      modest increases in maternal choline intake during pregnancy may produce
      cognitive benefits for offspring.-Caudill, M. A., Strupp, B. J., Muscalu, L.,
      Nevins, J. E. H., Canfield, R. L. Maternal choline supplementation during the
      third trimester of pregnancy improves infant information processing speed: a
      randomized, double-blind, controlled feeding study.

PMID- 29217671
TI  - Positive Change in Feedback Perceptions and Behavior: A 10-Year Follow-up Study.
AB  - BACKGROUND: Providing and learning from feedback are essential components of
      medical education, and typically described as resistant to change. But given a
      decade of change in the clinical context in which feedback occurs, the authors
      asked if, and how, perceptions of feedback and feedback behaviors might have
      changed in response to contextual affordances. METHODS: In 2017, the authors
      conducted a follow-up, ethnographic study on 2 general pediatric floors at the
      same children's hospital where another ethnographic study on a general pediatric
      floor was conducted in 2007. Data sources included (1) 21 and 34 hours of
      observation in 2007 and 2017, respectively, (2) 35 and 25 interviews with general
      pediatric attending physicians and residents in 2007 and 2017, respectively, and
      (3) a review of 120 program documents spanning 2007 to 2017. Data were coded and
      organized around 3 recommendations for feedback that were derived from 2007 data
      and served as standards for assessing change in 2017. RESULTS: Data revealed
      progress in achieving each recommendation. Compared with 2007, participants in
      2017 more clearly distinguished between feedback and evaluation; residents were
      more aware of in-the-moment feedback, and they had shifted their orientation from
      evaluation and grades to feedback and learning. Explanations for progress in
      achieving recommendations, which were derived from the data, pointed to
      institutional and national influences, namely, the pediatric milestones.
      CONCLUSIONS: On the basis of follow-up, ethnographic data, changes in the
      clinical context of pediatric education may afford positive change in perceptions
      of feedback and feedback behavior and point to influences within and beyond the
      institution.

PMID- 29217670
TI  - cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic
      Signaling Complexes.
AB  - It is widely accepted that cAMP signaling is compartmentalized within cells.
      However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and
      other key proteins form specific signaling complexes to regulate specific cell
      responses is limited. The multicomponent nature of these systems and the
      spatiotemporal dynamics involved as proteins interact and move within a cell make
      cAMP responses highly complex. Adenylyl cyclases, the enzymatic source of cAMP
      production, are key starting points for understanding cAMP compartments and
      defining the functional signaling complexes. Three basic elements are required to
      form a signaling compartment. First, a localized signal is generated by a G
      protein-coupled receptor paired to one or more of the nine different
      transmembrane adenylyl cyclase isoforms that generate the cAMP signal in the
      cytosol. The diffusion of cAMP is subsequently limited by several factors,
      including expression of any number of phosphodiesterases (of which there are 24
      genes plus spice variants). Finally, signal response elements are differentially
      localized to respond to cAMP produced within each locale. A-kinase-anchoring
      proteins, of which there are 43 different isoforms, facilitate this by targeting
      protein kinase A to specific substrates. Thousands of potential combinations of
      these three elements are possible in any given cell type, making the
      characterization of cAMP signaling compartments daunting. This review will focus
      on what is known about how cells organize cAMP signaling components as well as
      identify the unknowns. We make an argument for adenylyl cyclases being central to
      the formation and maintenance of these signaling complexes.

PMID- 29217672
TI  - Digital Ischemia After Application of Self-Adherent Elastic Wrap Dressing: A Case
      Series.
AB  - Self-adherent elastic wrap dressings are a convenient option to manage pediatric
      hand and finger injuries. However, when improperly applied, they have the
      potential to cause devastating complications. We detail in this report 5 cases of
      dressing-induced ischemic injury to the hand in pediatric patients with a review
      of the literature. All patients were treated by the senior author between 2007
      and 2015 and were retrospectively reviewed for initial injury, frequency of
      dressing changes, presence of pain, time to evaluation by the orthopedic hand
      team, treatment, and outcome. Patients' families were contacted for clinical
      updates and to obtain current photographs. Age at injury ranged from 11 months to
      3 years with 2 girls and 3 boys. Only 1 of 5 patients complained of pain or
      discomfort during the onset of their ischemic injury. Treatment of the ischemic
      injury included local wound care without surgery in 3 cases (including
      sympathetic block in 1) and surgical intervention with partial or complete
      digital amputation in 2 cases. At final follow-up, 2 of the 5 patients reported
      currently being bothered by the appearance of the injured hand; however, none had
      persistent pain or difficulty using the hand. Through these examples, health care
      professionals can be educated on the potentially disastrous complications of
      improper dressing application in the pediatric population and can be encouraged
      to share this information with patients' families.

PMID- 29217673
TI  - More than sixty origins of pantoporate pollen in angiosperms.
AB  - PREMISE OF THE STUDY: Apertures in pollen grains are key structures of the wall,
      involved in pollen tube germination and exchanges with the environment. Aperture
      types in angiosperms are diverse, but pollen with one and three apertures
      (including monosulcate and tricolpate, respectively) are the two most common
      types. Here, we investigate the phylogenetic distribution in angiosperms of
      pollen with many round, scattered apertures called pantoporate pollen. METHODS:
      We constructed a morphological data set with species producing pantoporate pollen
      and representative angiosperm species with other pollen types, sampled from every
      angiosperm order, with a total of 1260 species distributed in 330 families. This
      data set was analyzed with parsimony to characterize the phylogenetic
      distribution of pantoporate pollen in angiosperms. KEY RESULTS: We show that
      pantoporate pollen is distributed throughout most of the angiosperm tree,
      including early diverging angiosperms, monocots, and eudicots. However, this
      pollen type is usually restricted to a few species in a given group, and is
      seldom fixed at large taxonomical scales, with a few notable exceptions.
      CONCLUSIONS: Pantoporate pollen evolved many times during angiosperm history, but
      the persistence of this morphology in the long term is infrequent. This
      distribution pattern could indicate conflicting short-term and long-term
      selective pressures, pantoporate pollen being selected in the short run, but
      eliminated in the long run. Biological hypotheses supporting this scenario are
      discussed, in the context of both theoretical and empirical data on pollen
      biology.

PMID- 29217674
TI  - Pollen-pistil interaction in pawpaw (Asimina triloba), the northernmost species
      of the mainly tropical family Annonaceae.
AB  - PREMISE OF THE STUDY: The pawpaw, Asimina triloba, is an underutilized fruit crop
      native to North America that belongs to the mainly tropical, early-divergent
      family Annonaceae. Asimina is the only genus within the Annonaceae with species
      adapted to cold climates. A thorough analysis of its reproductive biology,
      specifically pollen-pistil interaction during the progamic phase, is essential to
      understand both its adaptation to cold climates and how to optimize its
      fertilization and fruit set. METHODS: We characterized pollen-pistil interaction
      in Asimina triloba, including the floral cycle and anatomy, stigmatic
      receptivity, and the pollen tube pathway. We used a combination of histological,
      cytological, and immunolocalization approaches. KEY RESULTS: Asimina triloba has
      a gynoecium formed by plicate carpels with a short stylar canal. Unicellular
      papillae form a continuous tissue covered by a copious secretion from the stigma
      to the ovary, which is most prominent on the stigma surface where it forms an
      extragynoecial compitum. Compared to the stigmas of other species in the
      Annonaceae, the stigmas of A. triloba show a long stigmatic receptivity
      associated with a long flowering cycle. Stigmatic receptivity is concomitant with
      the secretion of cell-wall-related arabinogalactan proteins (AGPs). CONCLUSIONS:
      A long female phase with a long period of stigmatic receptivity is unusual among
      protogynous flowers of the magnoliid clade, suggesting a derived condition of A.
      triloba within the Annonaceae. This phase further correlates with the presence of
      cell-wall-related arabinogalactan proteins in the secretion, which may indicate
      the conservation of these glycoproteins during stigmatic receptivity and pollen
      tube growth in angiosperms.

PMID- 29217676
TI  - Improvements in Outcomes and Disparities of ST-Segment-Elevation Myocardial
      Infarction Care: The Miami-Dade County ST-Segment-Elevation Myocardial Infarction
      Network Project.

PMID- 29217677
TI  - RCGP bans Babylon from sponsoring annual conference.

PMID- 29217675
TI  - Ten-Year Mortality in the WISE Study (Women's Ischemia Syndrome Evaluation).
AB  - BACKGROUND: The WISE study (Women's Ischemia Syndrome Evaluation) was a
      prospective cohort study of 936 clinically stable symptomatic women who underwent
      coronary angiography to evaluate symptoms and signs of ischemia. Long-term
      mortality data for such women are limited. METHODS AND RESULTS: Obstructive
      coronary artery disease (CAD) was defined as >=50% stenosis on angiography by
      core laboratory. We conducted a National Death Index search to assess the
      mortality of women who were alive at their final WISE contact date. Death
      certificates were obtained. All deaths were adjudicated as cardiovascular or
      noncardiovascular by a panel of WISE cardiologists masked to angiographic data.
      Multivariate Cox proportional hazards regression was used to identify significant
      independent predictors of mortality. At baseline, mean age was 58+/-12 years; 176
      (19%) were non-white, primarily black; 25% had a history of diabetes mellitus,
      59% hypertension, 55% dyslipidemia, and 59% had a body mass index >=30. During a
      median follow-up of 9.5 years (range, 0.2-11.5 years), a total of 184 (20%) died.
      Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths
      occurred in women without obstructive CAD (<50% stenosis). Independent predictors
      of mortality were obstructive CAD, age, baseline systolic blood pressure, history
      of diabetes mellitus, history of smoking, elevated triglycerides, and estimated
      glomerular filtration rate. CONCLUSIONS: Among women referred for coronary
      angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly
      cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the
      factors contributing to the risk of death seem to be modifiable by existing
      therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without
      obstructive CAD, a condition often considered benign and without guideline
      recommended treatments. Clinical trials are needed to provide treatment guidance
      for the group without obstructive CAD.

PMID- 29217679
TI  - Miz1 Controls Schwann Cell Proliferation via H3K36me2 Demethylase Kdm8 to Prevent
      Peripheral Nerve Demyelination.
AB  - Schwann cell differentiation and myelination depends on chromatin remodeling,
      histone acetylation, and methylation, which all affect Schwann cell
      proliferation. We previously reported that the deletion of the POZ (POxvirus and
      Zinc finger) domain of the transcription factor Miz1 (Myc-interacting zinc finger
      protein; encoded by Zbtb17) in mouse Schwann cells (Miz1DeltaPOZ) causes a
      neuropathy at 90 d after birth [postnatal day (P) 90], with a subsequent
      spontaneous regeneration. Here we show that RNA sequencing from Miz1DeltaPOZ and
      control animals at P30 revealed a set of upregulated genes with a strong
      correlation to cell-cycle regulation. Consistently, a subset of Schwann cells did
      not exit the cell cycle as observed in control animals and the growth fraction
      increased over time. From the RNAseq gene list, two direct Miz1 target genes were
      identified, one of which encodes the histone H3K36me2 demethylase Kdm8. We show
      that the expression of Kdm8 is repressed by Miz1 and that its release in
      Miz1DeltaPOZ cells induces a decrease of H3K36me2, especially in deregulated cell
      cycle-related genes. The linkage between elevated Kdm8 expression,
      hypomethylation of H3K36 at cell-cycle-relevant genes, and the subsequent re
      entering of adult Schwann cells into the cell cycle suggests that the release of
      Kdm8 repression in the absence of a functional Miz1 is a central issue in the
      development of the Miz1DeltaPOZ phenotype.SIGNIFICANCE STATEMENT The deletion of
      the Miz1 (Myc-interacting zinc finger protein 1) POZ (POxvirus and Zinc finger)
      domain in Schwann cells causes a neuropathy. Here we report sustained Schwann
      cell proliferation caused by an increased expression of the direct Miz1 target
      gene Kdm8, encoding a H3K36me2 demethylase. Hence, the demethylation of H3K36 is
      linked to the pathogenesis of a neuropathy.

PMID- 29217678
TI  - HRPU-2, a Homolog of Mammalian hnRNP U, Regulates Synaptic Transmission by
      Controlling the Expression of SLO-2 Potassium Channel in Caenorhabditis elegans.
AB  - Slo2 channels are large-conductance potassium channels abundantly expressed in
      the nervous system. However, it is unclear how their expression level in neurons
      is regulated. Here we report that HRPU-2, an RNA-binding protein homologous to
      mammalian heterogeneous nuclear ribonucleoprotein U (hnRNP U), plays an important
      role in regulating the expression of SLO-2 (a homolog of mammalian Slo2) in
      Caenorhabditis elegans Loss-of-function (lf) mutants of hrpu-2 were isolated in a
      genetic screen for suppressors of a sluggish phenotype caused by a hyperactive
      SLO-2. In hrpu-2(lf) mutants, SLO-2-mediated delayed outward currents in neurons
      are greatly decreased, and neuromuscular synaptic transmission is enhanced. These
      mutant phenotypes can be rescued by expressing wild-type HRPU-2 in neurons. HRPU
      2 binds to slo-2 mRNA, and hrpu-2(lf) mutants show decreased SLO-2 protein
      expression. In contrast, hrpu-2(lf) does not alter the expression of either the
      BK channel SLO-1 or the Shaker type potassium channel SHK-1. hrpu-2(lf) mutants
      are indistinguishable from wild type in gross motor neuron morphology and
      locomotion behavior. Together, these observations suggest that HRPU-2 plays
      important roles in SLO-2 function by regulating SLO-2 protein expression, and
      that SLO-2 is likely among a restricted set of proteins regulated by HRPU-2.
      Mutations of human Slo2 channel and hnRNP U are strongly linked to epileptic
      disorders and intellectual disability. The findings of this study suggest a
      potential link between these two molecules in human patients.SIGNIFICANCE
      STATEMENT Heterogeneous nuclear ribonucleoprotein U (hnRNP U) belongs to a family
      of RNA-binding proteins that play important roles in controlling gene expression.
      Recent studies have established a strong link between mutations of hnRNP U and
      human epilepsies and intellectual disability. However, it is unclear how
      mutations of hnRNP U may cause such disorders. This study shows that mutations of
      HRPU-2, a worm homolog of mammalian hnRNP U, result in dysfunction of a Slo2
      potassium channel, which is critical to neuronal function. Because mutations of
      Slo2 channels are also strongly associated with epileptic encephalopathies and
      intellectual disability in humans, the findings of this study point to a
      potential mechanism underlying neurological disorders caused by hnRNP U
      mutations.

PMID- 29217680
TI  - Non-Newly Generated, "Immature" Neurons in the Sheep Brain Are Not Restricted to
      Cerebral Cortex.
AB  - A newly proposed form of brain structural plasticity consists of non-newly
      generated, "immature" neurons of the adult cerebral cortex. Similar to newly
      generated neurons, these cells express the cytoskeletal protein Doublecortin
      (DCX), yet they are generated prenatally and then remain in a state of immaturity
      for long periods. In rodents, the immature neurons are restricted to the
      paleocortex, whereas in other mammals, they are also found in neocortex. Here, we
      analyzed the DCX-expressing cells in the whole sheep brain of both sexes to
      search for an indicator of structural plasticity at a cellular level in a
      relatively large-brained, long-living mammal. Brains from adult and newborn sheep
      (injected with BrdU and analyzed at different survival times) were processed for
      DCX, cell proliferation markers (Ki-67, BrdU), pallial/subpallial developmental
      origin (Tbr1, Sp8), and neuronal/glial antigens for phenotype characterization.
      We found immature-like neurons in the whole sheep cortex and in large populations
      of DCX-expressing cells within the external capsule and the surrounding gray
      matter (claustrum and amygdala). BrdU and Ki-67 detection at neonatal and adult
      ages showed that all of these DCX+ cells were generated during embryogenesis, not
      after birth. These results show that the adult sheep, unlike rodents, is largely
      endowed with non-newly generated neurons retaining immature features, suggesting
      that such plasticity might be particularly important in large-brained, long
      living mammals.SIGNIFICANCE STATEMENT Brain plasticity is important in adaptation
      and brain repair. Structural changes span from synaptic plasticity to adult
      neurogenesis, the latter being highly reduced in large-brained, long-living
      mammals (e.g., humans). The cerebral cortex contains "immature" neurons, which
      are generated prenatally and then remain in an undifferentiated state for long
      periods, being detectable with markers of immaturity. We studied the distribution
      and developmental origin of these cells in the whole brain of sheep, relatively
      large-brained, long-living mammals. In addition to the expected cortical
      location, we also found populations of non-newly generated neurons in several
      subcortical regions (external capsule, claustrum, and amygdala). These results
      suggests that non-neurogenic, parenchymal structural plasticity might be more
      important in large mammals with respect to adult neurogenesis.

PMID- 29217681
TI  - The Protein Tyrosine Phosphatase Shp2 Regulates Oligodendrocyte Differentiation
      and Early Myelination and Contributes to Timely Remyelination.
AB  - Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to
      influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation.
      Furthermore, Shp2 is a known regulator of the Akt/mammalian target of rapamycin
      and ERK signaling pathways in multiple cellular contexts, including
      oligodendrocytes. Its role during later postnatal CNS development or in response
      to demyelination injury has not been examined. Based on the current studies, we
      hypothesize that Shp2 is a negative regulator of CNS myelination. Using
      transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte
      differentiation and early myelination, but is not necessary for myelin
      maintenance. We also show that Shp2 regulates the timely differentiation of
      oligodendrocytes following lysolecithin-induced demyelination, although
      apparently normal remyelination occurs at a delayed time point. These data
      suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such
      as multiple sclerosis.SIGNIFICANCE STATEMENT In the present study, we show that
      the protein phosphatase Shp2 is an important mediator of oligodendrocyte
      differentiation and myelination, both during developmental myelination as well as
      during myelin regeneration. We provide important insight into the signaling
      mechanisms regulating myelination and propose that Shp2 acts as a transient brake
      to the developmental myelination process. Furthermore, we show that Shp2
      regulates oligodendrocyte differentiation following demyelination and therefore
      has important therapeutic implications in diseases such as multiple sclerosis.

PMID- 29217682
TI  - Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell
      Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety.
AB  - Repeated exposure to cocaine induces lasting epigenetic changes in neurons that
      promote the development and persistence of addiction. One epigenetic alteration
      involves reductions in levels of the histone dimethyltransferase G9a in nucleus
      accumbens (NAc) after chronic cocaine administration. This reduction in G9a may
      enhance cocaine reward because overexpressing G9a in the NAc decreases cocaine
      conditioned place preference. Therefore, we hypothesized that HSV-mediated G9a
      overexpression in the NAc shell (NAcSh) would attenuate cocaine self
      administration (SA) and cocaine-seeking behavior. Instead, we found that G9a
      overexpression, and the resulting increase in histone 3 lysine 9 dimethylation
      (H3K9me2), increases sensitivity to cocaine reinforcement and enhances motivation
      for cocaine in self-administering male rats. Moreover, when G9a overexpression is
      limited to the initial 15 d of cocaine SA training, it produces an enduring
      postexpression enhancement in cocaine SA and prolonged (over 5 weeks) increases
      in reinstatement of cocaine seeking induced by foot-shock stress, but in the
      absence of continued global elevations in H3K9me2. The increase in stress-induced
      reinstatement is paralleled by heightened anxiety measures, suggesting that
      countering the cocaine-induced decreases in endogenous G9a with ectopic G9a
      overexpression leads to lasting anxiogenic effects. Finally, we found an enduring
      reduction in phosphorylated cAMP-response element binding protein levels in the
      NAcSh that could account for the increased anxiety. These data demonstrate a
      novel role for G9a in promoting comorbid cocaine addiction and anxiety and
      suggest that increased epigenetic repression of transcription through H3K9 during
      cocaine use can have long-lasting and unexpected negative consequences on
      behavior.SIGNIFICANCE STATEMENT Cocaine addiction is a neuropsychiatric disorder
      that is detrimental to society and currently has no effective treatments. The
      difficulty in treating drug addiction is compounded by the high comorbidity with
      other psychiatric illnesses, including anxiety disorders. Here, we demonstrate
      that G9a, an epigenetic repressor of gene expression, acting in the nucleus
      accumbens, a brain reward region, is capable of increasing both addiction- and
      anxiety-like behaviors in rats. These findings are intriguing because repeated
      cocaine exposure decreases G9a in this region and thereby enhances expression of
      certain addiction-promoting genes. However, our results suggest that countering
      this cocaine-induced decrease in G9a activity actually exacerbates addiction and
      sensitivity to relapse under stressful situations.

PMID- 29217684
TI  - Retrieval Demands Adaptively Change Striatal Old/New Signals and Boost Subsequent
      Long-Term Memory.
AB  - The striatum is a central part of the dopaminergic mesolimbic system and
      contributes both to the encoding and retrieval of long-term memories. In this
      regard, the co-occurrence of striatal novelty and retrieval success effects in
      independent studies underlines the structure's double duty and suggests dynamic
      contextual adaptation. To test this hypothesis and further investigate the
      underlying mechanisms of encoding and retrieval dynamics, human subjects viewed
      pre-familiarized scene images intermixed with new scenes and classified them as
      indoor versus outdoor (encoding task) or old versus new (retrieval task), while
      fMRI and eye tracking data were recorded. Subsequently, subjects performed a
      final recognition task. As hypothesized, striatal activity and pupil size
      reflected task-conditional salience of old and new stimuli, but, unexpectedly,
      this effect was not reflected in the substantia nigra and ventral tegmental area
      (SN/VTA), medial temporal lobe, or subsequent memory performance. Instead,
      subsequent memory generally benefitted from retrieval, an effect possibly driven
      by task difficulty and activity in a network including different parts of the
      striatum and SN/VTA. Our findings extend memory models of encoding and retrieval
      dynamics by pinpointing a specific contextual factor that differentially
      modulates the functional properties of the mesolimbic system.SIGNIFICANCE
      STATEMENT The mesolimbic system is involved in the encoding and retrieval of
      information but it is unclear how these two processes are achieved within the
      same network of brain regions. In particular, memory retrieval and novelty
      encoding were considered in independent studies, implying that novelty (new >
      old) and retrieval success (old > new) effects may co-occur in the striatum.
      Here, we used a common framework implicating the striatum, but not other parts of
      the mesolimbic system, in tracking context-dependent salience of old and new
      information. The current study, therefore, paves the way for a more comprehensive
      understanding of the functional properties of the mesolimbic system during memory
      encoding and retrieval.

PMID- 29217683
TI  - Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like
      Phenotypes in Mice.
AB  - Autism spectrum disorder (ASD) is a developmental disability characterized by
      impairments in social interaction and repetitive behavior, and is also associated
      with cognitive deficits. There is no current treatment that can ameliorate most
      of the ASD symptomatology; thus, identifying novel therapies is urgently needed.
      We used male BTBR T+Itpr3tf /J (BTBR) mice, a model that reproduces most of the
      core behavioral phenotypes of ASD, to test the effects of systemic administration
      of insulin-like growth factor II (IGF-II), a polypeptide that crosses the blood
      brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II
      treatments reverse the typical defects in social interaction, cognitive/executive
      functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR
      mice, IGF-II, via IGF-II receptor, but not via IGF-I receptor, reverses the
      abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at
      synapses. Thus, IGF-II may represent a novel potential therapy for
      ASD.SIGNIFICANCE STATEMENT Currently, there is no effective treatment for autism
      spectrum disorder (ASD), a developmental disability affecting a high number of
      children. Using a mouse model that expresses most of the key core as well as
      associated behavioral deficits of ASD, that are, social, cognitive, and
      repetitive behaviors, we report that a systemic administration of the polypeptide
      insulin-like growth factor II (IGF-II) reverses all these deficits. The effects
      of IGF-II occur via IGF-II receptors, and not IGF-I receptors, and target both
      basal and learning-dependent molecular abnormalities found in several ASD mice
      models, including those of identified genetic mutations. We suggest that IGF-II
      represents a potential novel therapeutic target for ASD.

PMID- 29217685
TI  - Scale-Free Amplitude Modulation of Neuronal Oscillations Tracks Comprehension of
      Accelerated Speech.
AB  - Speech comprehension is preserved up to a threefold acceleration, but
      deteriorates rapidly at higher speeds. Current models posit that perceptual
      resilience to accelerated speech is limited by the brain's ability to parse
      speech into syllabic units using delta/theta oscillations. Here, we investigated
      whether the involvement of neuronal oscillations in processing accelerated speech
      also relates to their scale-free amplitude modulation as indexed by the strength
      of long-range temporal correlations (LRTC). We recorded MEG while 24 human
      subjects (12 females) listened to radio news uttered at different comprehensible
      rates, at a mostly unintelligible rate and at this same speed interleaved with
      silence gaps. delta, theta, and low-gamma oscillations followed the nonlinear
      variation of comprehension, with LRTC rising only at the highest speed. In
      contrast, increasing the rate was associated with a monotonic increase in LRTC in
      high-gamma activity. When intelligibility was restored with the insertion of
      silence gaps, LRTC in the delta, theta, and low-gamma oscillations resumed the
      low levels observed for intelligible speech. Remarkably, the lower the individual
      subject scaling exponents of delta/theta oscillations, the greater the
      comprehension of the fastest speech rate. Moreover, the strength of LRTC of the
      speech envelope decreased at the maximal rate, suggesting an inverse relationship
      with the LRTC of brain dynamics when comprehension halts. Our findings show that
      scale-free amplitude modulation of cortical oscillations and speech signals are
      tightly coupled to speech uptake capacity.SIGNIFICANCE STATEMENT One may read
      this statement in 20-30 s, but reading it in less than five leaves us clueless.
      Our minds limit how much information we grasp in an instant. Understanding the
      neural constraints on our capacity for sensory uptake is a fundamental question
      in neuroscience. Here, MEG was used to investigate neuronal activity while
      subjects listened to radio news played faster and faster until becoming
      unintelligible. We found that speech comprehension is related to the scale-free
      dynamics of delta and theta bands, whereas this property in high-gamma
      fluctuations mirrors speech rate. We propose that successful speech processing
      imposes constraints on the self-organization of synchronous cell assemblies and
      their scale-free dynamics adjusts to the temporal properties of spoken language.

PMID- 29217686
TI  - Synaptic Regulator alpha-Synuclein in Dopaminergic Fibers Is Essentially Required
      for the Maintenance of Subependymal Neural Stem Cells.
AB  - Synaptic protein alpha-synuclein (alpha-SYN) modulates neurotransmission in a
      complex and poorly understood manner and aggregates in the cytoplasm of
      degenerating neurons in Parkinson's disease. Here, we report that alpha-SYN
      present in dopaminergic nigral afferents is essential for the normal cycling and
      maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult
      male and female mice. We also show that premature senescence of adult NSCs into
      non-neurogenic astrocytes in mice lacking alpha-SYN resembles the effects of
      dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4
      phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic
      alpha-SYN. Interestingly, NSC loss in alpha-SYN-deficient mice can be prevented
      by viral delivery of human alpha-SYN into their sustantia nigra or by treatment
      with l-DOPA, suggesting that alpha-SYN regulates dopamine availability to NSCs.
      Our data indicate that alpha-SYN, present in dopaminergic nerve terminals
      supplying the subependymal zone, acts as a niche component to sustain the
      neurogenic potential of adult NSCs and identify alpha-SYN and DA as potential
      targets to ameliorate neurogenic defects in the aging and diseased
      brain.SIGNIFICANCE STATEMENT We report an essential role for the protein alpha
      synuclein present in dopaminergic nigral afferents in the regulation of adult
      neural stem cell maintenance, identifying the first synaptic regulator with an
      implication in stem cell niche biology. Although the exact role of alpha
      synuclein in neural transmission is not completely clear, our results indicate
      that it is required for stemness and the preservation of neurogenic potential in
      concert with dopamine.

PMID- 29217687
TI  - Role of the Axon Initial Segment in the Control of Spontaneous Frequency of
      Nigral Dopaminergic Neurons In Vivo.
AB  - The spontaneous tonic discharge activity of nigral dopamine neurons plays a
      fundamental role in dopaminergic signaling. To investigate the role of neuronal
      morphology and architecture with respect to spontaneous activity in this
      population, we visualized the 3D structure of the axon initial segment (AIS)
      along with the entire somatodendritic domain of adult male mouse dopaminergic
      neurons, previously recorded in vivo We observed a positive correlation of the
      firing rate with both proximity and size of the AIS. Computational modeling
      showed that the size of the AIS, but not its position within the somatodendritic
      domain, is the major causal determinant of the tonic firing rate in the intact
      model, by virtue of the higher intrinsic frequency of the isolated AIS. Further
      mechanistic analysis of the relationship between neuronal morphology and firing
      rate showed that dopaminergic neurons function as a coupled oscillator whose
      frequency of discharge results from a compromise between AIS and somatodendritic
      oscillators. Thus, morphology plays a critical role in setting the basal tonic
      firing rate, which in turn could control striatal dopaminergic signaling that
      mediates motivation and movement.SIGNIFICANCE STATEMENT The frequency at which
      nigral dopamine neurons discharge action potentials sets baseline dopamine levels
      in the brain, which enables activity in motor, cognitive, and motivational
      systems. Here, we demonstrate that the size of the axon initial segment, a
      subcellular compartment responsible for initiating action potentials, is a key
      determinant of the firing rate in these neurons. The axon initial segment and all
      the molecular components that underlie its critical function may provide a novel
      target for the regulation of dopamine levels in the brain.

PMID- 29217688
TI  - Sustained MAPK/ERK Activation in Adult Schwann Cells Impairs Nerve Repair.
AB  - The MAPK/ERK pathway has a critical role in PNS development. It is required for
      Schwann cell (SC) differentiation and myelination; sustained embryonic MAPK/ERK
      activation in SCs enhances myelin growth overcoming signals that normally end
      myelination. Excess activation of this pathway can be maladaptive as in adulthood
      acute strong activation of MAPK/ERK has been shown to cause SC dedifferentiation
      and demyelination. We used a mouse model (including male and female animals) in
      which the gain-of-function MEK1DD allele produces sustained MAPK/ERK activation
      in adult SCs, and we determined the impact of such activation on nerve repair. In
      the uninjured nerve, MAPK/ERK activation neither impaired myelin nor reactivated
      myelination. However, in the injured nerve it was detrimental and resulted in
      delayed repair and functional recovery. In the early phase of injury, the rate of
      myelin clearance was faster. Four weeks following injury, when nerve repair is
      normally advanced, myelinated axons of MEK1DD mutants demonstrated higher rates
      of myelin decompaction, a reduced number of Cajal bands. and decreased internodal
      length. We noted the presence of abnormal Remak bundles with long SCs processes
      and reduced numbers of C-fibers/Remak bundle. Both the total number of
      regenerating axons and the intraepidermal nerve fiber density in the skin were
      reduced. Sustained activation of MAPK/ERK in adult SCs is therefore deleterious
      to successful nerve repair, emphasizing the differences in the signaling
      processes coordinating nerve development and repair. Our results also underline
      the key role of SCs in axon regeneration and successful target
      reinnervation.SIGNIFICANCE STATEMENT The MAPK/ERK pathway promotes developmental
      myelination and its sustained activation in SCs induced continuous myelin growth,
      compensating for the absence of essential myelination signals. However, the
      strength of activation is fundamental because acute strong induction of MAPK/ERK
      in adulthood induces demyelination. What has been unknown is the effect of a mild
      but sustained MAPK/ERK activation in SCs on nerve repair in adulthood. This
      promoted myelin clearance but led to abnormalities in nonmyelinating and
      myelinating SCs in the later phases of nerve repair, resulting in slowed axon
      regeneration, cutaneous reinnervation, and functional recovery. Our results
      emphasize the distinct role of the MAPK/ERK pathway in developmental myelination
      versus remyelination and the importance of signaling between SCs and axons for
      successful axon regeneration.

PMID- 29217689
TI  - Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA Is Conveyed through
      Wide-Field Amacrine Cells.
AB  - The vertebrate retina has the remarkable ability to support visual function under
      conditions of limited illumination, including the processing of signals evoked by
      single photons. Dim-light vision is regulated by several adaptive mechanisms. The
      mechanism explored in this study is responsible for increasing the light
      sensitivity and operational range of rod bipolar cells, the retinal neurons
      operating immediately downstream of rod photoreceptors. This sensitization is
      achieved through the sustained dopamine-dependent GABA release from other retinal
      neurons. Our goals were to identify the cell type responsible for the GABA
      release and the site of its modulation by dopamine. Previous studies have
      suggested the involvement of amacrine and/or horizontal cells. We now
      demonstrate, using mice of both sexes, that horizontal cells do not participate
      in this mechanism. Instead, sustained GABA input is provided by a subpopulation
      of wide-field amacrine cells, which stimulate the GABAC receptors at rod bipolar
      cell axons. We also found that dopamine does not act directly on either of these
      cells. Rather, it suppresses inhibition imposed on these wide-field cells by
      another subpopulation of upstream GABAergic amacrine cells, thereby sustaining
      the GABAC receptor activation required for rod bipolar cell
      sensitization.SIGNIFICANCE STATEMENT The vertebrate retina has an exquisite
      ability to adjust information processing to ever-changing conditions of ambient
      illumination, from bright sunlight to single-photon counting under dim starlight.
      Operation under each of these functional regimes requires an engagement of
      specific adaptation mechanisms. Here, we describe a mechanism optimizing the
      performance of the dim-light channel of vision, which consists of sensitizing rod
      bipolar cells by a sustained GABAergic input originating from a population of
      wide-field amacrine cells. Wide-field amacrine cells span large segments of the
      retina, making them uniquely equipped to normalize and optimize response
      sensitivity across distant receptive fields and preclude any bias toward local
      light-intensity fluctuations.

PMID- 29217691
TI  - First-Line Osimertinib Beneficial in Advanced NSCLC.
AB  - Osimertinib is more effective as first-line therapy than other EGFR inhibitors
      for patients with advanced EGFR-mutated non-small cell lung cancer-notably
      Asians, who have a higher incidence of the disease compared with Western
      populations. The conclusion is based on data from a subgroup analysis of the
      phase III FLAURA trial.

PMID- 29217690
TI  - Repositioning of Somatic Golgi Apparatus Is Essential for the Dendritic
      Establishment of Adult-Born Hippocampal Neurons.
AB  - New dentate granule cells (DGCs) are continuously generated, and integrate into
      the preexisting hippocampal network in the adult brain. How an adult-born neuron
      with initially simple spindle-like morphology develops into a DGC, consisting of
      a single apical dendrite with further branches, remains largely unknown. Here,
      using retroviruses to birth date and manipulate newborn neurons, we examined
      initial dendritic formation and possible underlying mechanisms. We found that GFP
      expressing newborn cells began to establish a DGC-like morphology at ~7 d after
      birth, with a primary dendrite pointing to the molecular layer, but at this
      stage, with several neurites in the neurogenic zone. Interestingly, the Golgi
      apparatus, an essential organelle for neurite growth and maintenance, was
      dynamically repositioning in the soma of newborn cells during this initial
      integration stage. Two weeks after birth, by which time most neurites in the
      neurogenic zone were eliminated, a compact Golgi apparatus was positioned
      exclusively at the base of the primary dendrite. We analyzed the presence of
      Golgi-associated genes using single-cell transcriptomes of newborn DGCs, and
      among Golgi-related genes, found the presence of STK25 and STRAD, regulators of
      embryonic neuronal development. When we knocked down either of these two
      proteins, we found Golgi mislocalization and extensive aberrant dendrite
      formation. Furthermore, overexpression of a mutated form of STRAD, underlying the
      disorder polyhydramnios, megalencephaly, and symptomatic epilepsy, characterized
      by abnormal brain development and intractable epilepsy, caused similar defects in
      Golgi localization and dendrite formation in adult-born neurons. Together, our
      findings reveal a role for Golgi repositioning in regulating the initial
      integration of adult-born DGCs.SIGNIFICANCE STATEMENT Since the discovery of the
      continuous generation of new neurons in the adult hippocampus, extensive effort
      was directed toward understanding the functional contribution of these newborn
      neurons to the existing hippocampal circuit and associated behaviors, while the
      molecular mechanisms controlling their early morphological integration are less
      well understood. Dentate granule cells (DGCs) have a single, complex, apical
      dendrite. The events leading adult-born DGCs' to transition from simple spindle
      like morphology to mature dendrite morphology are largely unknown. We studied
      establishment of newborn DGCs dendritic pattern and found it was mediated by a
      signaling pathway regulating precise localization of the Golgi apparatus.
      Furthermore, this Golgi-associated mechanism for dendrite establishment might be
      impaired in a human genetic epilepsy syndrome, polyhydramnios, megalencephaly,
      and symptomatic epilepsy.

PMID- 29217692
TI  - Brexit could mean delays for cancer treatments and less safe medicines.

PMID- 29217693
TI  - Skin rash in a preterm infant: when to treat?

PMID- 29217694
TI  - Updated birth weight centiles for England and Wales.
AB  - OBJECTIVES: Construct updated birth weight-for-gestational age centile charts for
      use in the UK and compare these to the currently used UK-WHO charts. DESIGN:
      Secondary analysis of national birth data. PARTICIPANTS: Centiles were
      constructed using 1 269 403 singleton births occurring in England and Wales in
      2013-2014 as part of the MBRRACE-UK national perinatal surveillance programme.
      These were then validated using 642 737 singleton births occurring in England and
      Wales in 2015. MAIN OUTCOME MEASURES: Sex-specific birth weight-for-gestational
      age centiles. Centiles were created using the lambda-mu-sigma method via the
      GAMLSS package in R. This method transforms the skewed birth weight distribution
      to approximate a normal distribution, allowing any birth weight centile to be
      produced. RESULTS: The new centiles performed well in the validation sample, with
      the observed and expected proportion of births below a given centile in
      agreement. Overall, driven by the predominance of term births, the UK-WHO charts
      classify a smaller proportion of infants as below a given centile. For example,
      the UK-WHO estimates classified only 1.32% (8035/606 430) of term infants born in
      2015 as below the second centile, compared with 1.97% (11 975/606 430) using the
      new MBRRACE-UK centiles. At the earliest gestational ages, however, the opposite
      is observed, with the UK-WHO classifying a larger proportion of infants as below
      a given centile, particularly at the lower end of the birthweight distribution.
      CONCLUSIONS: We have constructed and validated updated birth weight-for
      gestational age centiles using a contemporary sample of births occurring in
      England and Wales. The benefits of these updated centiles will be first to assist
      the national surveillance of perinatal mortality programme by improving the
      identification of the proportion of stillbirths and neonatal deaths affected by
      intrauterine growth restriction and, second, to aid clinicians by more accurately
      identifying babies who require increased monitoring in the period immediately
      following birth.

PMID- 29217696
TI  - Raising up the voices of the closest observers of care.

PMID- 29217695
TI  - Harmonizing Methods for Estimating the Impact of Contraceptive Use on Unintended
      Pregnancy, Abortion, and Maternal Health.
AB  - Estimates of the potential impacts of contraceptive use on averting unintended
      pregnancies, total and unsafe abortions, maternal deaths, and newborn, infant,
      and child deaths provide evidence of the value of investments in family planning
      programs and thus are critically important for policy makers, donors, and
      advocates alike. Several research teams have independently developed mathematical
      models that estimate the number of adverse health outcomes averted due to
      contraceptive use. However, each modeling approach was designed for different
      purposes, and as such the methodological assumptions, data inputs, and
      mathematical algorithms initially used in each model differed; consequently, the
      models did not produce comparable estimates for the same outcome indicators. To
      address this, a series of expert group meetings took place in which 5 models
      Adding it Up, Impact 2, ImpactNow, Reality Check, and FamPlan/Lives Saved Tool
      (LiST)-were reviewed and harmonized where possible. The group identified the main
      reasons for the inconsistencies in the estimates generated by the models for each
      of the adverse health outcome indicators. The group then worked together to align
      the methodologies for estimating numbers of unintended pregnancies, abortions,
      and maternal deaths averted due to contraceptive use, and reviewed the challenges
      with estimating the impact of contraceptive use on newborn, infant, and child
      deaths, including the lack of a conceptually clear pathway and rigorous evidence.
      The assumption that most influenced harmonization was the comparison pregnancy
      rate used by the models to estimate the counterfactual scenario-that is, if women
      who are currently using contraception were not using a method, how many would
      become pregnant? All the models now base this on the number of unintended
      pregnancies among women with unmet contraceptive need, bringing the estimates for
      unintended pregnancies, total and unsafe abortion, and maternal deaths much
      closer together. The agreed approaches have already been adopted by the Family
      Planning 2020 (FP2020) initiative and Track20, a project that supports FP2020.
      The experts will continue to update their models collaboratively to ensure that
      the most current estimation methodologies and data available are used. Valid and
      reliable methodologies for estimating these impacts from family planning are
      critically important, not only for advocacy to sustain resource allocation
      commitments but also to enable measurement and tracking of global development
      indicators. Conflicting estimates can be counterproductive to generating support
      for family planning programs, and this harmonization process has created a more
      unified voice for quantifying the benefits of family planning.

PMID- 29217697
TI  - T-PLL: another check on the venetoclax list?

PMID- 29217698
TI  - MCL-1 keeps a charming home for thymocytes.

PMID- 29217699
TI  - Marginal immunogenicity of factor VIII.

PMID- 29217700
TI  - Unusual finding of a megakaryocyte in a peripheral blood smear.

PMID- 29217701
TI  - Signet-ring histiocytes in typhoid fever.

PMID- 29217702
TI  - Meet the First Authors.

PMID- 29217703
TI  - A Recipe for T-Tubules in Human iPS Cell-Derived Cardiomyocytes.

PMID- 29217704
TI  - Arrhythmogenic Cardiomyopathy: Pathophysiology Beyond Cardiac Myocytes.

PMID- 29217705
TI  - Decreased Maternal Cardiac Glucose Oxidation: Taking One for the Fetus.

PMID- 29217706
TI  - United We Stand; Divided We Fibrillate?

PMID- 29217707
TI  - Circulating Thyroxine: A Major New Risk Marker for Atherosclerosis?

PMID- 29217708
TI  - Shine on, Young Physician-Scientist.

PMID- 29217709
TI  - Bradford C. Berk: Picking Good Questions.

PMID- 29217710
TI  - 2017 Lucian Award: John McMurray.

PMID- 29217711
TI  - Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai
      Translational Mission.

PMID- 29217712
TI  - CANTOS: A Gigantic Proof-of-Concept Trial.

PMID- 29217713
TI  - Letter by Gagat and Grzanka Regarding Article, "Neutrophil Activation of
      Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration
      and Vascular Injury".

PMID- 29217714
TI  - Response by Mittal et al to Letter Regarding Article, "Neutrophil Activation of
      Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration
      and Vascular Injury".

PMID- 29217715
TI  - Noncompaction in Mitochondrial Disorders.

PMID- 29217716
TI  - Response by Towbin and Jefferies to Letter Regarding Article, "Cardiomyopathies
      Due to Left Ventricular Noncompaction, Mitochondrial and Storage Diseases, and
      Inborn Errors of Metabolism".

PMID- 29217717
TI  - 2017 AHA Late-Breaking Basic Science Abstracts.

PMID- 29217718
TI  - Social networks, leisure activities and maximum tongue pressure: cross-sectional
      associations in the Nagasaki Islands Study.
AB  - OBJECTIVES: Social environment is often associated with health outcomes, but
      epidemiological evidence for its effect on oral frailty, a potential risk factor
      for aspiration, is sparse. This study aimed to assess the association between
      social environment and tongue pressure, as an important measure of oral function.
      The study focused on family structure, social networks both with and beyond
      neighbours, and participation in leisure activities. DESIGN: A population-based
      cross-sectional study. SETTING: Annual health check-ups in a rural community in
      Japan. PARTICIPANTS: A total of 1982 participants, all over 40 years old. Anyone
      with missing data for the main outcome (n=14) was excluded. OUTCOME MEASURES:
      Tongue pressure was measured three times, and the maximum tongue pressure was
      used for analysis. A multivariable adjusted regression model was used to
      calculate parameter estimates (B) for tongue pressure. RESULTS: Having a social
      network involving neighbours (B=2.43, P=0.0001) and taking part in leisure
      activities (B=1.58, P=0.005) were independently associated with higher tongue
      pressure, but there was no link with social networks beyond neighbours (B=0.23,
      P=0.77). Sex-specific analyses showed that for men, having a partner was
      associated with higher tongue pressure, independent of the number of people in
      the household (B=2.26, P=0.01), but there was no association among women (B=
      0.24, P=0.72; P-interaction=0.059). CONCLUSIONS: Having a social network
      involving neighbours and taking part in leisure activities were independently
      associated with higher tongue pressure. Marital status may be an important factor
      in higher tongue pressure in men.

PMID- 29217719
TI  - Can traditional risk factors explain the higher risk of cardiovascular disease in
      South Asians compared to Europeans in Norway and New Zealand? Two cohort studies.
AB  - OBJECTIVES: The objective was to prospectively examine potential differences in
      the risk of first cardiovascular disease (CVD) events between South Asians and
      Europeans living in Norway and New Zealand, and to investigate whether
      traditional risk factors could explain any differences. METHODS: We included
      participants (30-74 years) without prior CVD in a Norwegian (n=16 606) and a New
      Zealand (n=129 449) cohort. Ethnicity and cardiovascular risk factor information
      was linked with hospital registry data and cause of death registries to identify
      subsequent CVD events. We used Cox proportional hazards regression to investigate
      the relationship between risk factors and subsequent CVD for South Asians and
      Europeans, and to calculate age-adjusted HRs for CVD in South Asians versus
      Europeans in the two cohorts separately. We sequentially added the major CVD risk
      factors (blood pressure, lipids, diabetes and smoking) to study their explanatory
      role in observed ethnic CVD risk differences. RESULTS: South Asians had higher
      total cholesterol (TC)/high-density lipoprotein (HDL) ratio and more diabetes at
      baseline than Europeans, but lower blood pressure and smoking levels. South
      Asians had increased age-adjusted risk of CVD compared with Europeans (87%-92%
      higher in the Norwegian cohort and 42%-75% higher in the New Zealand cohort) and
      remained with significantly increased risk after adjusting for all major CVD risk
      factors. Adjusted HRs for South Asians versus Europeans in the Norwegian cohort
      were 1.57 (95% CI 1.19 to 2.07) in men and 1.76 (95% CI 1.09 to 2.82) in women.
      Corresponding figures for the New Zealand cohort were 1.64 (95% CI 1.43 to 1.88)
      in men and 1.39 (95% CI 1.11 to 1.73) in women. CONCLUSION: Differences in TC/HDL
      ratio and diabetes appear to explain some of the excess risk of CVD in South
      Asians compared with Europeans. Preventing dyslipidaemia and diabetes in South
      Asians may therefore help reduce their excess risk of CVD.

PMID- 29217720
TI  - Likelihood of death among hospital inpatients in New Zealand: prevalent cohort
      study.
AB  - OBJECTIVES: (1) To establish the likelihood of dying within 12 months for a
      cohort of hospital inpatients in New Zealand (NZ) on a fixed census date; (2) to
      identify associations between likelihood of death and key sociodemographic,
      diagnostic and service-related factors and (3) to compare results with, and
      extend findings of, a Scottish study undertaken for the same time period and
      census date. National databases of hospitalisations and death registrations were
      used, linked by unique health identifier. PARTICIPANTS: 6074 patients stayed
      overnight in NZ hospitals on the census date (10 April 2013), 40.8% of whom were
      aged >=65 years; 54.4% were women; 69.1% of patients were NZ European; 15.3% were
      Maori; 7.6% were Pacific; 6.1% were Asian and 1.9% were 'other'. SETTING: All NZ
      hospitals. RESULTS: 14.5% patients (n=878) had died within 12 months: 1.6% by 7
      days; 4.5% by 30 days; 8.0% by 3 months and 10.9% by 6 months. In logistic
      regression models, the strongest predictors of death within 12 months were: age
      >=80 years (OR=5.52(95% CI 4.31 to 7.07)); a history of cancer (OR=4.20(3.53 to
      4.98)); being Maori (OR=1.62(1.25 to 2.10)) and being admitted to a medical
      specialty, compared with a surgical specialty (OR=3.16(2.66 to 3.76)).
      CONCLUSION: While hospitals are an important site of end of life care in NZ,
      their role is less significant than in Scotland, where 30% of an inpatient cohort
      recruited using similar methods and undertaken on the same census date had died
      within 12 months. One reason for this finding may be the extended role of
      residential long-term care facilities in end of life care provision in NZ.

PMID- 29217721
TI  - Insights from Australians with respiratory disease living in the community with
      experience of self-managing through an emergency department 'near miss' for
      breathlessness: a strengths-based qualitative study.
AB  - OBJECTIVES: Breathlessness 'crises' in people with chronic respiratory conditions
      are a common precipitant for emergency department (ED) presentations, many of
      which might be avoided through improved self-management and support. This study
      sought insights from people with experience of ED 'near misses' where they
      considered going to the ED but successfully self-managed instead. DESIGN AND
      METHODS: A qualitative approach was used with a phenomenological orientation.
      Participants were eligible if they reported breathlessness on most days from a
      diagnosed respiratory condition and experience of >=1 ED near miss. Recruitment
      was through respiratory support groups and pulmonary rehabilitation clinics.
      Semistructured interviews were conducted with each participant via telephone or
      face-to-face. Questions focused on ED-related decision-making, information
      finding, breathlessness management and support. This analysis used an integrative
      approach and independent coding by two researchers. Lazarus and Cohen's
      Transactional Model of Stress and Coping informed interpretive themes. RESULTS:
      Interviews were conducted with 20 participants, 15 of whom had chronic
      obstructive pulmonary disease. Nineteen interviews were conducted via telephone.
      Analysis identified important factors in avoiding ED presentation to include
      perceived control over breathlessness, self-efficacy in coping with a crisis and
      desire not to be hospitalised. Effective coping strategies included: taking a
      project management approach that involved goal setting, monitoring and risk
      management; managing the affective dimension of breathlessness separately from
      the sensory perceptual and building three-way partnerships with primary care and
      respiratory services. CONCLUSIONS: In addition to teaching non-pharmacological
      and pharmacological management of breathlessness, interventions should aim to
      develop patients' generic self-management skills. Interventions to improve self
      efficacy should ensure this is substantiated by transfer of skills and support,
      including knowledge about when ED presentation is necessary. Complementary
      initiatives are needed to improve coordinated, person-centred care. Future
      research should seek ways to break the cyclical relationship between affective
      and sensory-perceptual dimensions of breathlessness.

PMID- 29217722
TI  - Successfully implementing and embedding guidelines to improve the nutrition and
      growth of preterm infants in neonatal intensive care: a prospective
      interventional study.
AB  - OBJECTIVES: We aimed to improve the nutritional care of preterm infants by
      developing a complex (multifaceted) intervention intended to translate current
      evidence into practice. We used the sociological framework of Normalization
      Process Theory (NPT), to guide implementation in order to embed the new practices
      into routine care. DESIGN: A prospective interventional study with a before and
      after methodology. PARTICIPANTS: Infants <30 weeks gestation or <1500 g at birth.
      SETTING: Tertiary neonatal intensive care unit. INTERVENTIONS: The intervention
      was introduced in phases: phase A (control period, January-August 2011); phase B
      (partial implementation; improved parenteral and enteral nutrition solutions,
      nutrition team, education, August-December 2011); phase C (full implementation;
      guidelines, screening tool, 'nurse champions', January-December 2012); phase D
      (postimplementation; January-June 2013). Bimonthly audits and staff NPT
      questionnaires were used to measure guideline compliance and 'normalisation',
      respectively. NPT Scores were used to guide implementation in real time. Data on
      nutrient intakes and growth were collected continuously. RESULTS: There were 52,
      36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline
      compliance exceeded 75% throughout the intervention period, peaking at 85%.
      Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15,
      p<0.03 for both), with a significant linear association between the two (r=0.21,
      p<0.01). There were significant improvements in daily protein intake and weight
      gain between birth and discharge in phases B and Ccompared with phase A (p<0.01
      for all), which were sustained into phase D. CONCLUSIONS: NPT and audit results
      suggest that the intervention was rapidly incorporated into practice, with high
      guideline compliance and accompanying improvements in protein intake and weight
      gain. NPT appears to offer an effective way of implementing new practices such
      that they lead to sustained changes in care. Complex interventions based on
      current evidence can improve both practice and clinical outcomes.

PMID- 29217723
TI  - 'At-risk' individuals' responses to direct to consumer advertising of
      prescription drugs: a nationally representative cross-sectional study.
AB  - OBJECTIVES: The factors determining individuals' self-reported behavioural
      responses to direct to consumer advertising of prescription drugs were explored
      with an emphasis on 'at-risk' individuals' responses. DESIGN: Nationally
      representative cross-sectional survey. SETTING: Community living adults in New
      Zealand. PARTICIPANTS: 2057 adults (51% women). PRIMARY OUTCOME MEASURES: Self
      reported behavioural responses to drug advertising (asking a physician for a
      prescription, asking a physician for more information about an illness, searching
      the internet for more information regarding an illness and asking a pharmacist
      for more information about a drug). METHODS: Multivariate logistic regressions
      determined whether participants' self-reported behavioural responses to drug
      advertising were predicted by attitudes towards advertising and drug advertising,
      judgements about safety and effectiveness of advertised drugs, self-reported
      health status, materialism, online search behaviour as well as demographic
      variables. RESULTS: Identifying as Indian and to a less extent Chinese, Maori and
      'other' ethnicities were the strongest predictors of one or more self-reported
      responses (ORs 1.76-5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90
      0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34-1.61,
      all Ps<0.001) and searching for medical information online (ORs 1.32-2.35, all
      Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01
      1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89-0.91,
      Ps<0.05) and higher materialism (ORs 1.02-1.03, Ps<0.01) also predicted one or
      more self-reported responses. CONCLUSIONS: Taken together, the findings suggest
      individuals, especially those who are 'at-risk' (ie, with poorer self-reported
      health status, older, less educated, lower income and ethnic minorities), may be
      more vulnerable to drug advertising and may make uninformed decisions
      accordingly. The outcomes raise significant concerns relating to the ethicality
      of drug advertising and suggest a need for stricter guidelines to ensure that
      drug advertisements provided by pharmaceutical companies are ethical.

PMID- 29217724
TI  - Correlation of impulsivity with self-harm and suicidal attempt: a community study
      of adolescents in Taiwan.
AB  - OBJECTIVES: The aim of this study was to investigate differences and similarities
      in risk factors for deliberate self-harm (DSH) and suicidal attempt (SA), and the
      role of impulsivity among a group of community adolescents. SETTING: This is a
      cross-sectional study conducted at high schools in Northern Taiwan. DATA AND
      PARTICIPANTS: We recruited grade 1 students from 14 high schools. A total of 5879
      participants (mean age 16.02 years, female adolescents: 57.7%) completed the
      online assessment. OUTCOME MEASURES: Participants completed online questionnaires
      about sociodemographic data, suicidality, history of DSH and SA, depressed mood,
      self-esteem, social support, family discord, impulsivity (Barratt Impulsiveness
      Scale Version 11 (BIS-11)) and the use of alcohol, tobacco and illicit drugs. A
      subsample was interviewed about lifetime SA, and the results were compared with
      those from the online questionnaires. RESULTS: In our sample, 25% of the students
      had lifetime DSH and 3.5% had lifetime SA. Two hundred and seventy-two students
      received face-to-face interviews. The concordance between the online
      questionnaires and interviews in terms of ascertaining cases of SA was moderate
      (concordance rate 82.76%; kappa value 0.59). Similar risk factors for DSH/SA
      among the whole sample included female gender, lower academic performance,
      depression, substance use (tobacco and alcohol) and low self-esteem. The BIS-11
      score was correlated with DSH. Factor 3 score of the BIS-11 (novelty seeking) was
      correlated with DSH in both boys and girls, whereas factor 2 score (lack of self
      control) was correlated with SA in boys. Social support was a protective factor
      against SA among the female adolescents. Gender modulated the association of
      impulsivity and DSH/SA. Associations between impulsivity and DSH and SA were
      particularly strong among boys. CONCLUSIONS: Risk factors for DSH and SA were
      similar, but not identical. Early identification of those at risk and appropriate
      interventions may be helpful.

PMID- 29217725
TI  - Atrial fibrillation in patients with severe mental disorders and the risk of
      stroke, fatal thromboembolic events and bleeding: a nationwide cohort study.
AB  - OBJECTIVES: Outcomes of atrial fibrillation (AF) in patients with severe mental
      disorders are largely unknown. We compared rates of stroke, fatal thromboembolic
      events and bleeding in patients with AF with and without mental disorders.
      DESIGN: Nationwide registry-based cohort study. SETTING: Denmark (population 5.6
      million), 2000-2015. PARTICIPANTS: Patients with AF with schizophrenia (n=534),
      severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and
      calendar time to patients with AF without mental disorders. EXPOSURE: Inpatient
      or hospital-based outpatient diagnosis of schizophrenia, severe depression or
      bipolar disease. PRIMARY AND SECONDARY OUTCOME MEASURES: HRs for stroke, fatal
      thromboembolic events and major bleeding comparing patients with and without
      mental disorders estimated by Cox regression with sequential adjustment for risk
      factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant
      therapy (OAT). RESULTS: Compared with matched comparisons, crude 5-year HRs of
      ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI
      0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease.
      After adjusting for risk factors, comorbidity and OAT, these HRs declined towards
      the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to
      5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95%
      CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in
      patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe
      depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95%
      CI 0.58 to 1.15). CONCLUSION: Patients with AF with schizophrenia or severe
      depression experienced increased rates of stroke and major bleeding compared with
      matched comparisons. This increase was largely explained by differences in the
      prevalence of risk factors for stroke and bleeding, comorbidity and initiation of
      OAT during follow-up. Patients with AF with schizophrenia further experienced
      higher mortality following thromboembolic events than matched comparisons without
      mental disorders.

PMID- 29217726
TI  - The association between the use of biomedical services and the holistic use of
      traditional East Asian medicine: a national survey of outpatients in South Korea.
AB  - OBJECTIVES: The holistic use of a system of complementary and alternative
      medicine (CAM) is potentially linked to its treatment outcomes. This paper
      examines how the use of biomedicine is associated with the holistic use of CAM,
      focusing on traditional East Asian medicine (EM) that is uniquely integrated in
      the medical system in South Korea. DESIGN/SETTINGS: A representative national
      sample of EM outpatients in South Korea. PARTICIPANTS: 3861 survey respondents.
      METHODS: By using the 2011 Korean National Survey of EM patients, ordered
      logistic regression models specify the relationship between EM outpatients' use
      of biomedicine and their holistic use of EM modalities. RESULTS: Among EM
      outpatients who used at least one EM modality in the past 3 months, people who
      used two (33.3%) or three (29.4%) modalities together are the two highest
      proportions, followed by users of four (18.1%), five (7.2%), six (2.1%) and seven
      (0.6%) modalities. The odds for EM users to use EM holistically are 17% greater
      among EM users who used biomedicine as well, compared with EM users who did not
      use biomedicine. CONCLUSIONS: The healthcare community should recognise that CAM
      use likely becomes holistic as people use biomedicine concomitantly, when the
      practice rights over a CAM system are comprehensively and exclusively entitled to
      a group of CAM professionals who are independent from practitioners of
      biomedicine.

PMID- 29217727
TI  - Advancing the science of health research capacity strengthening in low-income and
      middle-income countries: a scoping review of the published literature, 2000-2016.
AB  - OBJECTIVES: Substantial development assistance and research funding are invested
      in health research capacity strengthening (HRCS) interventions in low-income and
      middle-income countries, yet the effectiveness, impact and value for money of
      these investments are not well understood. A major constraint to evidence
      informed HRCS intervention has been the disparate nature of the research effort
      to date. This review aims to map and critically analyse the existing HRCS effort
      to better understand the level, type, cohesion and conceptual sophistication of
      the current evidence base. The overall goal of this article is to advance the
      development of a unified, implementation-focused HRCS science. METHODS: We used a
      scoping review methodology to identify peer-reviewed HRCS literature within the
      following databases: PubMed, Global Health and Scopus. HRCS publications
      available in English between the period 2000 and 2016 were included. 1195
      articles were retrieved of which 172 met the final inclusion criteria. A priori
      thematic analysis of all included articles was completed. Content analysis of
      identified HRCS definitions was conducted. RESULTS: The number of HRCS
      publications increased exponentially between 2000 and 2016. Most publications
      during this period were perspective, opinion or commentary pieces; however,
      original research publications were the primary publication type since 2013.
      Twenty-five different definitions of research capacity strengthening were
      identified, of which three aligned with current HRCS guidelines. CONCLUSIONS: The
      review findings indicate that an HRCS research field with a focus on
      implementation science is emerging, although the conceptual and empirical bases
      are not yet sufficiently advanced to effectively inform HRCS programme planning.
      Consolidating an HRCS implementation science therefore presents as a viable
      option that may accelerate the development of a useful evidence base to inform
      HRCS programme planning. Identifying an agreed operational definition of HRCS,
      standardising HRCS-related terminology, developing a needs-based HRCS-specific
      research agenda and synthesising currently available evidence may be useful first
      steps.

PMID- 29217728
TI  - Acupuncture for patients with vascular dementia: a systematic review protocol.
AB  - INTRODUCTION: This systematic review protocol aims to provide the methods used to
      evaluate the effectiveness and safety of acupuncture therapy for treating
      vascular dementia. METHODS AND ANALYSIS: The following eight databases will be
      searched from inception to July 2017: Cochrane Central Register of Controlled
      Trials, PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese
      Biomedical Literature Database, VIP Database and Wanfang Database. All randomised
      controlled trials in English or Chinese related to acupuncture for vascular
      dementia will be included. Outcomes will include change in cognitive function and
      activities of daily living. The incidence of adverse events will be assessed for
      safety evaluation. Study inclusion, data extraction and quality assessment will
      be performed independently by two reviewers. Assessment of risk of bias and data
      synthesis will be performed using Review Manager software. ETHICS AND
      DISSEMINATION: Ethics approval is not required because individual patient data
      are not included. The findings of this systematic review will be disseminated
      through peer-reviewed publication or conference presentations. PROSPERO
      REGISTRATION NUMBER: CRD42017071820.

PMID- 29217729
TI  - Bone marrow solid core biopsy needle: a critical assessment of the utility,
      benefits and limitations of the instruments employed in current day haematology
      and oncology.
AB  - The optimal clinical evaluation of the bone marrow requires an examination of air
      dried and well-stained films of the aspirated tissue along with a
      histopathological evaluation of adequately processed and properly stained core
      biopsy specimens. A bone marrow evaluation can be essential in establishing a
      diagnosis, determining the efficacy of treatment in haematological disorders and
      to monitor haematological status of patients following bone marrow/stem cell
      transplantation. It is also an essential component of the staging process for
      newly diagnosed malignancies. Currently available bone marrow aspiration needles
      are quite satisfactory and if properly used provide good-quality specimens for
      morphological evaluation. However, if a bone marrow core biopsy is concerned,
      several needles are currently in use but not all of them provide good-quality
      biopsy specimens for histological evaluation or are user friendly. We have
      compared the recently introduced Moeller Medical single use bone marrow core
      biopsy needle with the Jamshidi needle with marrow acquisition cradle
      (CareFusion), J-needle (Cardinal Health) and OnControl device (Vidacare). It is
      concluded that the Moeller Medical needle system has definite advantages over
      others and is recommended for routine use.

PMID- 29217730
TI  - In Vivo Functional Analysis of Drosophila Robo1 Fibronectin Type-III Repeats.
AB  - The repellant ligand Slit and its Roundabout (Robo) family receptors regulate
      midline crossing of axons during development of the embryonic central nervous
      system (CNS). Slit proteins are produced at the midline and signal through Robo
      receptors to repel axons from the midline. Disruption of Slit-Robo signaling
      causes ectopic midline-crossing phenotypes in the CNS of a broad range of
      animals, including insects and vertebrates. While previous studies have
      investigated the roles of Drosophila melanogaster Robo1's five Immunoglobulin
      like (Ig) domains, little is known about the importance of the three
      evolutionarily conserved Fibronectin (Fn) type-III repeats. We have individually
      deleted each of Drosophila Robo1's three Fn repeats, and then tested these Robo1
      variants in vitro to determine their ability to bind Slit in cultured Drosophila
      cells and in vivo to investigate the requirement for each domain in regulating
      Robo1's embryonic expression pattern, axonal localization, midline repulsive
      function, and sensitivity to Commissureless (Comm) downregulation. We demonstrate
      that the Fn repeats are not required for Robo1 to bind Slit or for proper
      expression of Robo1 in Drosophila embryonic neurons. When expressed in a robo1
      mutant background, these variants are able to restore midline repulsion to an
      extent equivalent to full-length Robo1. We identify a novel requirement for Fn3
      in the exclusion of Robo1 from commissures and downregulation of Robo1 by Comm.
      Our results indicate that each of the Drosophila Robo1 Fn repeats are
      individually dispensable for the protein's role in midline repulsion, despite the
      evolutionarily conserved "5 + 3" protein structure.

PMID- 29217732
TI  - Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy.
AB  - Immunotherapy has become a promising alternative therapeutic approach for cancer
      patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been
      verified to be a successful means for cancer therapy in clinical trials. mAb
      targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell
      lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the
      antibody can limit its application. In our study, targeting PD-L1 peptide (TPP
      1), which specifically binds to PD-L1 with high affinity, was identified through
      bacterial surface display methods. Using a T-cell activation assay and mixed
      lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD
      1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth in vivo, a
      xenograft mouse model using H460 cells was established. The growth rate of tumor
      masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in
      control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at
      least retards, tumor growth. IHC of the tumors showed that IFNgamma and granzyme
      B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating
      that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells
      may get reactivated. On the basis of our data, TPP-1 peptide could work as an
      alternative to antibodies for tumor immunotherapy. Cancer Immunol Res; 6(2); 178
      88. (c)2017 AACR.

PMID- 29217731
TI  - Genome-Wide Analysis of Grain Yield Stability and Environmental Interactions in a
      Multiparental Soybean Population.
AB  - Genetic improvement toward optimized and stable agronomic performance of soybean
      genotypes is desirable for food security. Understanding how genotypes perform in
      different environmental conditions helps breeders develop sustainable cultivars
      adapted to target regions. Complex traits of importance are known to be
      controlled by a large number of genomic regions with small effects whose
      magnitude and direction are modulated by environmental factors. Knowledge of the
      constraints and undesirable effects resulting from genotype by environmental
      interactions is a key objective in improving selection procedures in soybean
      breeding programs. In this study, the genetic basis of soybean grain yield
      responsiveness to environmental factors was examined in a large soybean nested
      association population. For this, a genome-wide association to performance
      stability estimates generated from a Finlay-Wilkinson analysis and the inclusion
      of the interaction between marker genotypes and environmental factors was
      implemented. Genomic footprints were investigated by analysis and meta-analysis
      using a recently published multiparent model. Results indicated that specific
      soybean genomic regions were associated with stability, and that multiplicative
      interactions were present between environments and genetic background. Seven
      genomic regions in six chromosomes were identified as being associated with
      genotype-by-environment interactions. This study provides insight into genomic
      assisted breeding aimed at achieving a more stable agronomic performance of
      soybean, and documented opportunities to exploit genomic regions that were
      specifically associated with interactions involving environments and
      subpopulations.

PMID- 29217733
TI  - Sex as a Biologic Variable in Preclinical Imaging Research: Initial Observations
      with 18F-FLT.
AB  - The study objective was to investigate whether sex influences 3'-deoxy-3'-18F
      fluorothymidine (18F-FLT) uptake and tissue distribution in mouse models of
      cancer. Methods:18F-FLT biodistribution was measured in 3 strains of male and
      female mice (129S6/SvEv, athymic nude, and BALB/c). 18F-FDG biodistribution was
      measured for comparison. 18F-FLT uptake was also measured in female 129S6/SvEv
      mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice
      bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female
      athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer
      xenografts. Ki-67 expression was assayed by immunohistochemistry. PET/CT imaging
      was performed to visualize 18F-FLT biodistribution and to determine
      pharmacokinetics. Results: Greater 18F-FLT activity was observed in blood, liver,
      muscle, heart, kidney, and bone in female than male mice. Pharmacokinetic
      analysis demonstrated higher early renal 18F-FLT activity and greater
      accumulation of 18F-FLT in the urinary bladder in male than female mice. The
      differential pattern of 18F-FLT biodistribution between the sexes seen with 18F
      FLT was not observed with 18F-FDG. Increased tumoral 18F-FLT uptake compared with
      muscle was observed in both the SSM3 mammary tumors (2.4 +/- 0.17 vs. 1.6 +/-
      0.14 percentage injected dose [%ID]/g at 2 h after injection, P = 0.006) and the
      CWR22 prostate cancer xenografts (0.34 +/- 0.08 vs. 0.098 +/- 0.033 %ID/g at 2 h
      after injection, P = 0.03). However, because of higher nonspecific muscle uptake
      in female mice, tumor-to-muscle uptake ratios were greater for CWR22 tumors than
      for SSM3 tumors (4.2 +/- 0.78 vs. 1.5 +/- 0.049 at 2 h after injection, P =
      0.008). Sex-dependent differences in 18F-FLT uptake were also observed for MDA-MB
      231 xenografts (tumor-to-muscle ratio, 7.2 +/- 0.9 for female vs. 16.9 +/- 8.6
      for male, P = 0.039). Conversely, greater tumoral Ki-67 staining was observed in
      female mice (71% +/- 3% for female vs. 54% +/- 2% for male, P = 0.009), and this
      finding more closely matched the relative differences in absolute 18F-FLT tumor
      uptake values (4.5 +/- 0.99 %ID/g for female vs. 1.9 +/- 0.30 %ID/g for male, P =
      0.03). Conclusion: Depending on whether female or male mice are used, differences
      in biodistribution and nonspecific tissue uptake can adversely affect
      quantitative measures of 18F-FLT uptake. Thus, sex is a potential variable to
      consider in defining quantitative imaging metrics using 18F-FLT to assess tumor
      proliferation.

PMID- 29217734
TI  - In Vivo Imaging of Pro- and Antitumoral Cellular Components of the Tumor
      Microenvironment.
AB  - Tumor development and growth, as well as metastatic spread, are strongly
      influenced by various, mostly innate, immune cells, which are recruited to the
      tumor site and driven to establish a specific tumor-supportive microenvironment.
      The contents of this microenvironment, such as myeloid cells, are a major factor
      in the overall prognosis of malignant disease, addressed by a constantly growing
      armament of therapeutic interventions targeting tumor-supportive immune cells.
      Current clinical imaging has long ignored the growing need for diagnostic
      approaches addressing these microenvironmental contents-approaches enabling a
      sensitive and specific classification of tumor immune crosstalk and the resulting
      tumor-associated immune cell activity. In this focus article we review the
      present status of, and promising developments in, the in vivo molecular imaging
      of tumor immune components designed to allow for inferences to be made on the
      cross-talk between tumor cells and the immune system. Current imaging modalities
      based on the infiltrating cell types are briefly discussed.

PMID- 29217735
TI  - Immuno-PET in Pontine Glioma: More Than Meets the Eye?

PMID- 29217736
TI  - Generation of Structural MR Images from Amyloid PET: Application to MR-Less
      Quantification.
AB  - Structural MR images concomitantly acquired with PET images can provide crucial
      anatomic information for precise quantitative analysis. However, in the clinical
      setting, not all the subjects have corresponding MR images. Here, we developed a
      model to generate structural MR images from amyloid PET using deep generative
      networks. We applied our model to quantification of cortical amyloid load without
      structural MR. Methods: We used florbetapir PET and structural MR data from the
      Alzheimer Disease Neuroimaging Initiative database. The generative network was
      trained to generate realistic structural MR images from florbetapir PET images.
      After the training, the model was applied to the quantification of cortical
      amyloid load. PET images were spatially normalized to the template space using
      the generated MR, and then SUV ratio (SUVR) of the target regions was measured by
      predefined regions of interest. A real MR-based quantification was used as the
      gold standard to measure the accuracy of our approach. Other MR-less methods-a
      normal PET template-based, a multiatlas PET template-based, and a PET
      segmentation-based normalization/quantification-were also tested. We compared the
      performance of quantification methods using generated MR with that of MR-based
      and MR-less quantification methods. Results: Generated MR images from florbetapir
      PET showed signal patterns that were visually similar to the real MR. The
      structural similarity index between real and generated MR was 0.91 +/- 0.04. The
      mean absolute error of SUVR of cortical composite regions estimated by the
      generated MR-based method was 0.04 +/- 0.03, which was significantly smaller than
      other MR-less methods (0.29 +/- 0.12 for the normal PET template, 0.12 +/- 0.07
      for the multiatlas PET template, and 0.08 +/- 0.06 for the PET segmentation-based
      methods). Bland-Altman plots revealed that the generated MR-based SUVR
      quantification was the closest to the SUVRs estimated by the real MR-based
      method. Conclusion: Structural MR images were successfully generated from amyloid
      PET images using deep generative networks. Generated MR images could be used as
      templates for accurate and precise amyloid quantification. This generative method
      might be used to generate multimodal images of various organs for further
      quantitative analyses.

PMID- 29217737
TI  - Is Exercise Treadmill Time or Reduction in Myocardial Ischemia the Appropriate
      Primary Endpoint to Assess Success of Percutaneous Coronary Intervention in
      Stable Angina (ORBITA)?

PMID- 29217738
TI  - Radiolabeled (4-Fluoro-3-Iodobenzyl)Guanidine Improves Imaging and Targeted
      Radionuclide Therapy of Norepinephrine Transporter-Expressing Tumors.
AB  - 18F- or 131I-labeled (4-fluoro-3-iodobenzyl)guanidine (FIBG) has been a promising
      yet unattainable derivative of radioiodine-labeled meta-iodobenzylguanidine
      (MIBG), because of the complex radiofluorination method. In this study, we
      proposed a 2-step radiosynthetic method to obtain 18F-FIBG and evaluated the
      diagnostic and therapeutic potential of 18F-FIBG and 131I-FIBG in a
      pheochromocytoma model (PC-12). Methods:18F-FIBG was prepared from a
      (mesityl)(aryl)iodonium salt precursor in the presence of a copper catalyst.
      Biodistribution studies, PET imaging, and a therapeutic study were performed on
      the PC-12 xenograft mice with either 18F- or 131I-FIBG. The association between
      the therapeutic effect and the tumor uptake of pretherapy 18F-FIBG PET was also
      evaluated. Results: The copper-mediated radiofluorination method readily yielded
      18F-FIBG, as well as its regioisomer, 18F-IFBG. The isolated 18F-FIBG showed a
      higher accumulation in the PC-12 xenograft tumor than in any other tissue. The
      high tumor uptake of 18F-FIBG allowed clear tumor visualization in the PET images
      as early as 1 h after injection, with an excellent tumor-to-background ratio. A
      biodistribution study with 131I-FIBG revealed its higher and prolonged retention
      in the tumor in comparison with 125I-MIBG. As a result, a therapeutic dose of
      131I-FIBG delayed tumor growth significantly more than did 131I-MIBG. The tumor
      uptake of 18F-FIBG was proportional to the therapeutic effect of 131I-FIBG.
      Conclusion: These results suggest the potential usefulness of FIBG as a
      diagnostic and therapeutic agent for the management of norepinephrine transporter
      (NET)-expressing tumors.

PMID- 29217739
TI  - 90Y Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal
      Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort.
AB  - We report survival outcomes for patients with advanced-stage hepatocellular
      carcinoma (HCC) with portal vein thrombosis (PVT) treated with 90Y
      radioembolization. Methods: With institutional review board approval, we searched
      our prospectively acquired database for 90Y patients treated between 2003 and
      2017. Inclusion criteria were patients who had HCC with tumor PVT. Patients with
      metastases were excluded. Laboratory data were collected at baseline and 1 mo
      after 90Y radioembolization. Toxicity grades were reported according to the
      Common Terminology Criteria for Adverse Events, version 4.0, and long-term
      survival outcomes were reported and stratified by Child-Pugh class (CP). Overall
      survival was calculated using the Kaplan-Meier method. Multivariate analysis was
      performed using Cox proportional hazards regression. A subanalysis for patients
      with a high level of alpha-fetoprotein (AFP) (>100 ng/dL) was conducted. Results:
      In total, 185 patients with HCC PVT underwent 90Y radioembolization. Seventy-four
      (40%) were CP-A, 51 (28%) were CP-B7, and 60 (32%) were >=CP-B8. New albumin,
      bilirubin, and alkaline phosphatase grade 3/4 toxicities were, respectively, 3%,
      10%, and 0% for CP-A; 14%, 12%, and 6% for CP-B7; and 23%, 32%, and 3% for >=CP
      B8. Median overall survival for CP-A patients was 13.3 mo (95% confidence
      interval [CI], 8.7-15.7 mo). CP-B7 and >=CP-B8 patients exhibited median overall
      survival of 6.9 mo (95% CI, 5.3-10.1 mo) and 3.9 mo (95% CI, 2.9-5.0 mo),
      respectively. Significant overall survival prognosticators on univariate analysis
      were albumin, bilirubin, ascites, tumor size 5 cm or smaller, focality,
      distribution, infiltration, Eastern Cooperative Oncology Group status, AFP level,
      and PVT extent. Multivariate analysis showed the prognosticators of overall
      survival to be bilirubin, no ascites, tumor size 5 cm or smaller, solitary
      lesion, baseline AFP level lower than 100 ng/dL, and Eastern Cooperative Oncology
      Group status. Of 123 patients with a high AFP level (>100 ng/dL), 12 patients
      achieved restored normal AFP levels (<13 ng/dL) and exhibited median overall
      survival of 23.9 mo (95% CI, 20.1-124.1 mo). AFP responders at 1 mo had better
      overall survival than nonresponders, at 8.5 mo versus 4.8 mo (P = 0.018); AFP
      responders at 3 mo had overall survival of 13.3 mo, versus 6.9 mo for
      nonresponders (P = 0.021). Conclusion:90Y radioembolization can serve as a safe
      and effective treatment for advanced-stage HCC patients with tumor PVT. Overall
      survival outcomes are affected by baseline liver function, tumor size, and AFP
      level.

PMID- 29217740
TI  - Optic Nerve Measurement on MRI in the Pediatric Population: Normative Values and
      Correlations.
AB  - BACKGROUND AND PURPOSE: Few articles in the literature have looked at the
      diameter of the optic nerve on MR imaging, especially in children, in whom
      observations are subjective and no normative data exist. The aim of this study
      was to establish a data base for optic nerve diameter measurements on MR imaging
      in the pediatric population. MATERIALS AND METHODS: This was a retrospective
      study on the MR imaging of pediatric subjects (younger than 18 years of age) at
      the Department of Diagnostic Radiology at the American University of Beirut
      Medical Center, Beirut, Lebanon. The optic nerve measurements were obtained by 3
      raters on axial and coronal sections at 3 mm (retrobulbar) and 7 mm
      (intraorbital) posterior to the lamina cribrosa. RESULTS: Of 211 scans of
      patients (422 optic nerves), 377 optic nerves were measured and included. Ninety
      four patients were female (45%) and the median age at MR imaging was 8.6 years
      (interquartile range, 3.9-13.3 years). Optic nerves were divided into 5 age
      groups: 0-6 months (n = 18), 6 months-2 years (n = 44), 2-6 years (n = 86), 6-12
      years (n = 120), and 12-18 years (n = 109). An increase in optic nerve diameter
      was observed with age, especially in the first 2 years of life. Measurements did
      not differ with eye laterality or sex. CONCLUSIONS: We report normative values of
      optic nerve diameter measured on MR imaging in children from birth to 18 years of
      age. A rapid increase in optic nerve diameter was demonstrated during the first 2
      years of life, followed by a slower increase. This was independent of sex or eye
      laterality.

PMID- 29217741
TI  - On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging
      in Cerebrovascular Disease.
AB  - BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both
      microvascular and parenchymal abnormalities simultaneously. The contamination of
      CSF signal can be suppressed using inversion recovery preparation. The clinical
      feasibility of inversion recovery-intravoxel incoherent motion imaging was
      investigated in patients with cerebrovascular disease by studying its
      reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular
      disease (66 +/- 8 years of age) underwent inversion recovery-intravoxel
      incoherent motion imaging twice. The reproducibility of the perfusion volume
      fraction and parenchymal diffusivity was calculated with the coefficient of
      variation, intraclass correlation coefficient, and the repeatability coefficient.
      ROIs included the normal-appearing white matter, cortex, deep gray matter, white
      matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion
      volume fraction ranged from 2.42 to 3.97 *10-2 and for parenchymal diffusivity
      from 7.20 to 9.11 * 10-4 mm2/s, with higher values found in the white matter
      hyperintensities and vascular lesions. Coefficients of variation were <3.70% in
      normal-appearing tissue and <9.15% for lesions. Intraclass correlation
      coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in
      all ROIs, except the deep gray matter and cortex, with intraclass correlation
      coefficients of 0.66 and 0.54, respectively. The repeatability coefficients
      ranged from 0.15 to 0.96 * 10-2 and 0.10 to 0.37 * 10-4 mm2/s for perfusion
      volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good
      reproducibility of inversion recovery-intravoxel incoherent motion imaging was
      observed with low coefficients of variation and high intraclass correlation
      coefficients in normal-appearing tissue and lesion areas in cerebrovascular
      disease. Good reproducibility of inversion recovery-intravoxel incoherent motion
      imaging in cerebrovascular disease is feasible in monitoring disease progression
      or treatment responses in the clinic.

PMID- 29217742
TI  - Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of
      Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.
AB  - BACKGROUND AND PURPOSE: Centrally restricted diffusion has been demonstrated in
      recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess
      the accuracy of centrally restricted diffusion in the diagnosis of radiation
      necrosis in high-grade gliomas not treated with bevacizumab. MATERIALS AND
      METHODS: In this prospective study, we enrolled patients with high-grade gliomas
      who developed a new ring-enhancing necrotic lesion and who underwent re
      resection. The presence of a centrally restricted diffusion within the ring
      enhancing lesion was assessed visually on diffusion trace images and by ADC
      measurements on 3T preoperative diffusion tensor examination. The percentage of
      tumor recurrence and radiation necrosis in each surgical specimen was defined
      histopathologically. The association between centrally restricted diffusion and
      radiation necrosis was assessed using the Fisher exact test. Differences in ADC
      and the ADC ratio between the groups were assessed via the Mann-Whitney U test,
      and receiver operating characteristic curve analysis was performed. RESULTS:
      Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation
      necrosis and 9 cases of tumor recurrence. There was significant association
      between centrally restricted diffusion by visual assessment and radiation
      necrosis (P = .015) with a sensitivity of 75% and a specificity of 88.9%, a
      positive predictive value 85.7%, and a negative predictive value of 80% for the
      diagnosis of radiation necrosis. There was a statistically significant difference
      in the ADC and ADC ratio between radiation necrosis and tumor recurrence (P =
      .027). CONCLUSIONS: The presence of centrally restricted diffusion in a new ring
      enhancing lesion might indicate radiation necrosis rather than tumor recurrence
      in high-grade gliomas previously treated with standard chemoradiation without
      bevacizumab.

PMID- 29217743
TI  - Dural Arteriovenous Fistulas: A Characteristic Pattern of Edema and Enhancement
      of the Medulla on MRI.
AB  - Medullary edema with enhancement is rarely reported at initial MR imaging in
      intracranial dural arteriovenous fistulas. We report a series of 5 patients with
      dural arteriovenous fistulas, all of whom demonstrated a characteristic pattern
      of central medullary edema and medullary enhancement at initial MR imaging.
      Cognard type V dural arteriovenous fistula, defined by drainage into the
      perimedullary veins and the veins surrounding the brain stem, is a rare yet well
      described pathologic entity. Even more rarely reported, however, is its clinical
      presentation with predominantly bulbar symptoms and MR imaging findings of
      central medullary edema with enhancement. This constellation of findings
      frequently leads to a convoluted clinical picture, prompting work-up for
      alternative disease processes and delaying diagnosis. Because an expedited
      diagnosis is critical in preventing poor outcomes, it is paramount to make the
      referring physician and neuroradiologist more cognizant of this rare-yet
      characteristic imaging manifestation of dural arteriovenous fistula.

PMID- 29217744
TI  - The CT Swirl Sign Is Associated with Hematoma Expansion in Intracerebral
      Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Hematoma expansion is an independent determinant of poor
      clinical outcome in intracerebral hemorrhage. Although the "spot sign" predicts
      hematoma expansion, the identification requires CT angiography, which limits its
      general accessibility in some hospital settings. Noncontrast CT, without the need
      for CT angiography, may identify sites of active extravasation, termed the "swirl
      sign." We aimed to determine the association of the swirl sign with hematoma
      expansion. MATERIALS AND METHODS: Patients with spontaneous intracerebral
      hemorrhage between 2007 and 2014 who underwent an initial and subsequent
      noncontrast CT at a single center were retrospectively identified. The swirl
      sign, on noncontrast CT, was defined as iso- or hypodensity within a hyperdense
      region that extended across 2 contiguous 5-mm axial CT sections. RESULTS: A total
      of 212 patients met the inclusion criteria. The swirl sign was identified in 91
      patients with excellent interobserver agreement (kappa = 0.87). The swirl sign
      was associated with larger initial hematoma (P < .001) and earlier initial CT (P
      < .001) and hematoma expansion (P = .028). Multivariable regression modeling
      demonstrated that if one assumed similar initial hematoma volume, onset-to-first
      scan, and time between CT scans, the median absolute hematoma growth was 5.77 mL
      (95% CI, 2.37-9.18 mL; P = .001) and relative growth was 35.6% (95% CI, 18.5%
      52.6%; P < .001) higher in patients with the swirl sign compared with those
      without. CONCLUSIONS: The NCCT swirl sign was reliably identified and is
      associated with hematoma expansion. We propose that the swirl sign be included in
      risk stratification of intracerebral hemorrhage and considered for inclusion in
      clinical trials.

PMID- 29217745
TI  - Intranasal Esthesioneuroblastoma: CT Patterns Aid in Preventing Routine Nasal
      Polypectomy.
AB  - BACKGROUND AND PURPOSE: Esthesioneuroblastoma is a neuroectodermal tumor that
      commonly arises in the nasal cavity olfactory recess and, when isolated to the
      intranasal cavity, can be indistinguishable from benign processes. Because
      lesional aggressiveness requires a more invasive operation for resection than
      polypectomy, patients with isolated intranasal lesions were studied to define
      distinguishing CT characteristics. MATERIALS AND METHODS: Patients with
      intranasal esthesioneuroblastoma and controls without esthesioneuroblastoma with
      olfactory recess involvement were identified by using a report search tool.
      Studies demonstrating skull base invasion and/or intracranial extension were
      excluded. The imaging spectrum of these lesions was reviewed on both CT and MR
      imaging, and CT findings were compared with those of controls without
      esthesioneuroblastoma. Two blinded readers assessed subjects with
      esthesioneuroblastomas and controls without esthesioneuroblastoma and, using only
      CT criteria, rated their level of suspicion for esthesioneuroblastoma in each
      case. RESULTS: Eight histologically proved cases of intranasal
      esthesioneuroblastoma were reviewed. All cases had CT demonstrating 3 main
      findings: 1) an intranasal polypoid lesion with its epicenter in a unilateral
      olfactory recess, 2) causing asymmetric olfactory recess widening, and 3)
      extending to the cribriform plate. Twelve patients with non-esthesioneuroblastoma
      diseases involving the olfactory recess were used as controls. Using these 3
      esthesioneuroblastoma CT criteria, 2 blinded readers evaluating patients with
      esthesioneuroblastoma and controls had good diagnostic accuracy (area under the
      curve = 0.85 for reader one, 0.81 for reader 2) for predicting
      esthesioneuroblastoma. CONCLUSIONS: Esthesioneuroblastoma can present as a well
      marginated intranasal lesion that unilaterally widens the olfactory recess. CT
      patterns can help predict esthesioneuroblastoma, potentially preventing multiple
      operations by instigating the correct initial operative management.

PMID- 29217746
TI  - Semiautomated Middle Ear Volume Measurement as a Predictor of Postsurgical
      Outcomes for Congenital Aural Atresia.
AB  - BACKGROUND AND PURPOSE: Middle ear space is one of the most important components
      of the Jahrsdoerfer grading system (J-score), which is used to determine surgical
      candidacy for congenital aural atresia. The purpose of this study was to
      introduce a semiautomated method for measuring middle ear volume and determine
      whether middle ear volume, either alone or in combination with the J-score, can
      be used to predict early postoperative audiometric outcomes. MATERIALS AND
      METHODS: A retrospective analysis was conducted of 18 patients who underwent an
      operation for unilateral congenital aural atresia at our institution. Using the
      Livewire Segmentation tool in the Carestream Vue PACS, we segmented middle ear
      volumes using a semiautomated method for all atretic and contralateral normal
      ears on preoperative high-resolution CT imaging. Postsurgical audiometric outcome
      data were then analyzed in the context of these middle ear volumes. RESULTS:
      Atretic middle ear volumes were significantly smaller than those in contralateral
      normal ears (P < .001). Patients with atretic middle ear volumes of >305 mm3 had
      significantly better postoperative pure tone average and speech reception
      thresholds than those with atretic ears below this threshold volume (P = .01 and
      P = .006, respectively). Atretic middle ear volume incorporated into the J-score
      offered the best association with normal postoperative hearing (speech reception
      threshold <= 30 dB; OR = 37.8, P = .01). CONCLUSIONS: Middle ear volume,
      calculated in a semiautomated fashion, is predictive of postsurgical audiometric
      outcomes, both independently and in combination with the conventional J-score.

PMID- 29217747
TI  - MR Perfusion to Determine the Status of Collaterals in Patients with Acute
      Ischemic Stroke: A Look Beyond Time Maps.
AB  - BACKGROUND AND PURPOSE: Patients with acute stroke with robust collateral flow
      have better clinical outcomes and may benefit from endovascular treatment
      throughout an extended time window. Using a multiparametric approach, we aimed to
      identify MR perfusion parameters that can represent the extent of collaterals,
      approximating DSA. MATERIALS AND METHODS: Patients with anterior circulation
      proximal arterial occlusion who had baseline MR perfusion and DSA were evaluated.
      The volume of arterial tissue delay (ATD) at thresholds of 2-6 seconds (ATD2-6
      seconds) and >6 seconds (ATD>6 seconds) in addition to corresponding values of
      normalized CBV and CBF was calculated using VOI analysis. The association of MR
      perfusion parameters and the status of collaterals on DSA were assessed by
      multivariate analyses. Receiver operating characteristic analysis was performed.
      RESULTS: Of 108 patients reviewed, 39 met our inclusion criteria. On DSA, 22/39
      (56%) patients had good collaterals. Patients with good collaterals had
      significantly smaller baseline and final infarct volumes, smaller volumes of
      severe hypoperfusion (ATD>6 seconds), larger volumes of moderate hypoperfusion
      (ATD2-6 seconds), and higher relative CBF and relative CBV values than patients
      with insufficient collaterals. Combining the 2 parameters into a Perfusion
      Collateral Index (volume of ATD2-6 seconds * relative CBV2-6 seconds) yielded the
      highest accuracy for predicting collateral status: At a threshold of 61.7, this
      index identified 15/17 (88%) patients with insufficient collaterals and 22/22
      (100%) patients with good collaterals, for an overall accuracy of 94.1%.
      CONCLUSIONS: The Perfusion Collateral Index can predict the baseline collateral
      status with 94% diagnostic accuracy compared with DSA.

PMID- 29217748
TI  - Lower Arterial Cross-Sectional Area of Carotid and Vertebral Arteries and Higher
      Frequency of Secondary Neck Vessels Are Associated with Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Arterial and neck vessel system characteristics of
      patients with multiple sclerosis have not been previously investigated.
      Therefore, the aim of this study was to examine the frequency of neck vessels and
      their cross-sectional areas (in square millimeters) between patients with MS and
      healthy controls. MATERIALS AND METHODS: In this study, 193 patients with MS and
      193 age- and sex-matched healthy controls underwent 2D TOF venography at 3T. The
      main arterial (carotid and vertebral), venous (internal jugular), and secondary
      neck vessels were examined at 4 separate cervical levels (C2/3, C4, C5/6, and
      C7/T1). The ANCOVA adjusted for age, body mass index, smoking status,
      hypertension, and heart disease was used to compare the differences between
      patients with MS and healthy controls. RESULTS: After controlling for all
      confounding factors, patients with MS had significantly lower cross-sectional
      areas of the carotid arteries at the C2/3 (P = .03), C5/6 (P = .026), and C7/T1
      (P = .005) levels as well as of the vertebral arteries at the C2/3 (P = .02), C4
      (P = .012), and C7/T1 (P = .006) levels, compared with healthy controls. A higher
      frequency of secondary neck vessels was found at all 4 levels in patients with
      MS: C2/3 (12.9 versus 10, P < .001), C4 (9.1 versus 7.5, P < .001), C5/6 (7.8
      versus 6.8, P = .012), and C7/T1 (8.8 versus 6, P < .001). The total cross
      sectional areas of secondary neck vessels were also significantly higher at all 4
      levels (P < .03). No significant differences in the cross-sectional areas of
      jugular veins were found between patients with MS and healthy controls.
      CONCLUSIONS: Patients with MS showed lower cross-sectional areas of the carotid
      and vertebral arteries and a higher frequency of secondary neck vessels and their
      cross-sectional areas compared with healthy controls.

PMID- 29217749
TI  - Hepatitis delta virus persists during liver regeneration and is amplified through
      cell division both in vitro and in vivo.
AB  - OBJECTIVE: Hepatitis delta virus (HDV) was shown to persist for weeks in the
      absence of HBV and for months after liver transplantation, demonstrating the
      ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to
      evaluate the impact of cell proliferation on HDV persistence in vitro and in
      vivo. DESIGN: Genetically labelled human sodium taurocholate cotransporting
      polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with
      HBV/HDV and passaged every 7 days for 100 days in the presence of the entry
      inhibitor Myrcludex-B. In vivo, cell proliferation was triggered by transplanting
      primary human hepatocytes (PHHs) isolated from HBV/HDV-infected humanised mice
      into naive recipients. Virological parameters were measured by quantitative real
      time polymerase chain reaction (qRT-PCR). Hepatitis delta antigen (HDAg),
      hepatitis B core antigen (HBcAg) and cell proliferation were determined by
      immunofluorescence. RESULTS: Despite 15 in vitro cell passages and block of viral
      spreading by Myrcludex-B, clonal cell expansion permitted amplification of HDV
      infection. In vivo, expansion of PHHs isolated from HBV/HDV-infected humanised
      mice was confirmed 3 days, 2, 4 and 8 weeks after transplantation. While HBV
      markers rapidly dropped in proliferating PHHs, HDAg-positive hepatocytes were
      observed among dividing cells at all time points. Notably, HDAg-positive cells
      appeared in clusters, indicating that HDV was transmitted to daughter cells
      during liver regeneration even in the absence of de novo infection. CONCLUSION:
      This study demonstrates that HDV persists during liver regeneration by
      transmitting HDV RNA to dividing cells even in the absence of HBV coinfection.
      The strong persistence capacities of HDV may also explain why HDV clearance is
      difficult to achieve in HBV/HDV chronically infected patients.

PMID- 29217750
TI  - Overcoming immune evasion in pancreatic cancer: the combination matters.

PMID- 29217751
TI  - Cellular basis of brain maturation and acquisition of complex behaviors in
      salamanders.
AB  - The overall bauplan of the tetrapod brain is highly conserved, yet significant
      variations exist among species in terms of brain size, structural composition and
      cellular diversity. Understanding processes underlying neural and behavioral
      development in a wide range of species is important both from an evolutionary
      developmental perspective as well as for the identification of cell sources with
      post-developmental neurogenic potential. Here, we characterize germinal processes
      in the brain of Notophthalmus viridescens and Pleurodeles waltl during both
      development and adulthood. Using a combination of cell tracking tools, including
      clonal analyses in new transgenic salamander lines, we examine the origin of
      neural stem and progenitor cells found in the adult brain, determine regional
      variability in cell cycle length of progenitor cells, and show spatiotemporally
      orchestrated neurogenesis. We analyze how maturation of different brain regions
      and neuronal subpopulations are linked to the acquisition of complex behaviors,
      and how these behaviors are altered upon chemical ablation of dopamine neurons.
      Our data analyzed from an evolutionary perspective reveal both common and species
      specific processes in tetrapod brain formation and function.

PMID- 29217752
TI  - Mapping the distribution of stem/progenitor cells across the mouse middle ear
      during homeostasis and inflammation.
AB  - The middle ear epithelium is derived from neural crest and endoderm, which line
      distinct regions of the middle ear cavity. Here, we investigate the distribution
      of putative stem cell markers in the middle ear, combined with an analysis of the
      location of label-retaining cells (LRCs) to create a map of the middle ear
      mucosa. We show that proliferating cells and LRCs were associated with specific
      regions of the ear epithelium, concentrated in the hypotympanum at the base of
      the auditory bulla and around the ear drum. Sox2 was widely expressed in the
      endodermally derived ciliated pseudostratified epithelium of the hypotympanum.
      This part of the middle ear showed high levels of Wnt activity, as indicated by
      the expression of Axin2, a readout of Wnt signalling. Keratin 5 showed a more
      restricted expression within the basal cells of this region, with very little
      overlap between the Sox2- and keratin 5-positive epithelium, indicating that
      these genes mark distinct populations. Little expression of Sox2 or keratin 5 was
      observed in the neural crest-derived middle ear epithelium that lined the
      promontory, except in cases of otitis media when this epithelium underwent
      hyperplasia. This study lays the foundation for furthering our understanding of
      homeostasis and repair in the middle ear.

PMID- 29217753
TI  - Wnt inhibition promotes vascular specification of embryonic cardiac progenitors.
AB  - Several studies have demonstrated a multiphasic role for Wnt signaling during
      embryonic cardiogenesis and developed protocols that enrich for cardiac
      derivatives during in vitro differentiation of human pluripotent stem cells
      (hPSCs). However, few studies have investigated the role of Wnt signaling in the
      specification of cardiac progenitor cells (CPCs) toward downstream fates. Using
      transgenic mice and hPSCs, we tracked endothelial cells (ECs) that originated
      from CPCs expressing NKX2.5. Analysis of EC-fated CPCs at discrete phenotypic
      milestones during hPSC differentiation identified reduced Wnt activity as a
      hallmark of EC specification, and the enforced activation or inhibition of Wnt
      reduced or increased, respectively, the degree of vascular commitment within the
      CPC population during both hPSC differentiation and mouse embryogenesis. Wnt5a,
      which has been shown to exert an inhibitory influence on Wnt signaling during
      cardiac development, was dynamically expressed during vascular commitment of hPSC
      derived CPCs, and ectopic Wnt5a promoted vascular specification of hPSC-derived
      and mouse embryonic CPCs.

PMID- 29217754
TI  - ERECTA-family genes coordinate stem cell functions between the epidermal and
      internal layers of the shoot apical meristem.
AB  - The epidermal cell layer and the tissues that lie underneath have different
      intrinsic functions during plant development. The stem cells within the shoot
      apical meristem (SAM) that give rise to aerial structures are located in the
      epidermal and internal tissue layers. However, our understanding of how the
      functions of these stem cells are coordinated across tissue layers so stem cells
      can behave as a single population remains limited. WUSCHEL (WUS) functions as a
      master regulator of stem cell activity. Here, we show that loss of function in
      the ERECTA (ER)-family receptor kinase genes can rescue the mutant phenotype of
      wus plants (loss of stem cells), as demonstrated by the reinstated expression of
      a stem cell marker gene in the SAM epidermis. Localized ER expression in the
      epidermis can suppress the SAM phenotype caused by loss of ER-family activity.
      Furthermore, the CLAVATA3- and cytokinin-induced outputs, which contribute to
      stem cell homeostasis, are dysfunctional in a tissue layer-specific manner in ER
      family mutants. Collectively, our findings suggest that the ER family plays a
      role in the coordination of stem cell behavior between different SAM tissue
      layers.

PMID- 29217755
TI  - Pollen differentiation as well as pollen tube guidance and discharge are
      independent of the presence of gametes.
AB  - After meiosis, an unequal cell division generates the male gamete lineage in
      flowering plants. The generative cell will undergo a second division, giving rise
      to the two gametes, i.e. the sperm cells. The other cell will develop into the
      vegetative cell that plays a crucial role in pollen tube formation and sperm
      delivery. Recently, the vegetative cell has been suggested to be important for
      programming of the chromatin state in sperm cells and/or the resulting
      fertilization products. Blocking the initial unequal division genetically, we
      first highlight that the default differentiation state after male meiosis is a
      vegetative fate, which is consistent with earlier work. We find that uni
      nucleated mutant microspores differentiated as wild-type vegetative cells,
      including chromatin remodeling and the transcriptional activation of transposable
      elements. Moreover, live-cell imaging revealed that this vegetative cell is
      sufficient for the correct guidance of the pollen tube to the female gametes.
      Hence, we conclude that vegetative cell differentiation and function does not
      depend on the formation or presence of the actual gametes but rather on external
      signals or a cell-autonomous pace keeper.

PMID- 29217756
TI  - Light-focusing human micro-lenses generated from pluripotent stem cells model
      lens development and drug-induced cataract in vitro.
AB  - Cataracts cause vision loss and blindness by impairing the ability of the ocular
      lens to focus light onto the retina. Various cataract risk factors have been
      identified, including drug treatments, age, smoking and diabetes. However, the
      molecular events responsible for these different forms of cataract are ill
      defined, and the advent of modern cataract surgery in the 1960s virtually
      eliminated access to human lenses for research. Here, we demonstrate large-scale
      production of light-focusing human micro-lenses from spheroidal masses of human
      lens epithelial cells purified from differentiating pluripotent stem cells. The
      purified lens cells and micro-lenses display similar morphology, cellular
      arrangement, mRNA expression and protein expression to human lens cells and
      lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770
      reduces micro-lens transparency and focusing ability. These human micro-lenses
      provide a powerful and large-scale platform for defining molecular disease
      mechanisms caused by cataract risk factors, for anti-cataract drug screening and
      for clinically relevant toxicity assays.

PMID- 29217758
TI  - Targeting Myocardial Energetics in the Failing Heart: Are We There Yet?

PMID- 29217757
TI  - Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized,
      Placebo-Controlled Trial of Elamipretide.
AB  - BACKGROUND: Mitochondrial dysfunction and energy depletion in the failing heart
      are innovative therapeutic targets in heart failure management. Elamipretide is a
      novel tetrapeptide that increases mitochondrial energy; however, its safety,
      tolerability, and therapeutic effect on cardiac structure and function have not
      been studied in heart failure with reduced ejection fraction. METHODS AND
      RESULTS: In this double-blind, placebo-controlled, ascending-dose trial, patients
      with heart failure with reduced ejection fraction (ejection fraction, <=35%) were
      randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8],
      0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg.kg-1.h-1) or placebo
      control (n=12). Safety and efficacy were assessed by clinical, laboratory, and
      echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8
      , 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide
      occurred at end-infusion and were undetectable by 24 hours postinfusion. There
      were no serious adverse events. Blood pressure and heart rate remained stable in
      all cohorts. Compared with placebo, a significant decrease in left ventricular
      end-diastolic volume (-18 mL; P=0.009) and end-systolic volume (-14 mL; P=0.005)
      occurred at end infusion in the highest dose cohort. CONCLUSIONS: This is the
      first study to evaluate elamipretide in heart failure with reduced ejection
      fraction and demonstrates that a single infusion of elamipretide is safe and well
      tolerated. High-dose elamipretide resulted in favorable changes in left
      ventricular volumes that correlated with peak plasma concentrations, supporting a
      temporal association and dose-effect relationship. Further study of elamipretide
      is needed to determine long-term safety and efficacy. CLINICAL TRIAL
      REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT02388464.

PMID- 29217759
TI  - Opposing Roles of Dendritic Cell Subsets in Experimental GN.
AB  - Dendritic cells (DCs) are thought to form a dendritic network across barrier
      surfaces and throughout organs, including the kidney, to perform an important
      sentinel function. However, previous studies of DC function used markers, such as
      CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs
      in renal inflammation using a CD11c reporter mouse line and two mouse lines with
      DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney
      sections confirmed that most of the dendritically shaped CD11c+ cells forming a
      network throughout the renal interstitium expressed macrophage-specific markers.
      In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant,
      concentrated around blood vessels, and round in shape. We confirmed this pattern
      of localization using imaging mass cytometry. Motility measurements showed that
      resident macrophages were sessile, whereas DCs were motile before and after
      inflammation. Although uninflamed glomeruli rarely contained DCs, injury with
      nephrotoxic antibodies resulted in accumulation of ZBTB46 + cells in the
      periglomerular region. ZBTB46 identifies all classic DCs, which can be
      categorized into two functional subsets that express either CD103 or CD11b.
      Depletion of ZBTB46 + cells attenuated the antibody-induced kidney injury,
      whereas deficiency of the CD103+ subset accelerated injury through a mechanism
      that involved increased neutrophil infiltration. RNA sequencing 7 days after
      nephrotoxic antibody injection showed that CD11b+ DCs expressed the neutrophil
      attracting cytokine CXCL2, whereas CD103+ DCs expressed high levels of several
      anti-inflammatory genes. These results provide new insights into the distinct
      functions of the two major DC subsets in glomerular inflammation.

PMID- 29217760
TI  - Tumor-Associated Fatigue in Cancer Patients Develops Independently of IL1
      Signaling.
AB  - Fatigue is the most common symptom of cancer at diagnosis, yet causes and
      effective treatments remain elusive. As tumors can be highly inflammatory, it is
      generally accepted that inflammation mediates cancer-related fatigue. However,
      evidence to support this assertion is mostly correlational. In this study, we
      directly tested the hypothesis that fatigue results from propagation of tumor
      induced inflammation to the brain and activation of the central proinflammatory
      cytokine, IL1. The heterotopic syngeneic murine head and neck cancer model (mEER)
      caused systemic inflammation and increased expression of Il1b in the brain while
      inducing fatigue-like behaviors characterized by decreased voluntary wheel
      running and exploratory activity. Expression of Il1b in the brain was not
      associated with any alterations in motivation, measured by responding in a
      progressive ratio schedule of food reinforcement, depression-like behaviors, or
      energy balance. Decreased wheel running occurred prior to Il1b detection in the
      brain, when systemic inflammation was minimal. Furthermore, mice null for two
      components of IL1beta signaling, the type 1 IL1 receptor or the receptor adapter
      protein MyD88, were not protected from tumor-induced decreases in wheel running,
      despite attenuated cytokine action and expression. Behavioral and inflammatory
      analysis of four additional syngeneic tumor models revealed that tumors can
      induce fatigue regardless of their systemic or central nervous system
      inflammatory potential. Together, our results show that brain IL1 signaling is
      not necessary for tumor-related fatigue, dissociating this type of cancer sequela
      from systemic cytokine expression.Significance: These findings challenge the
      current understanding of fatigue in cancer patients, the most common and
      debilitating sequela associated with malignancy. Cancer Res; 78(3); 695-705.
      (c)2017 AACR.

PMID- 29217761
TI  - Aptamer-Conjugated Extracellular Nanovesicles for Targeted Drug Delivery.
AB  - Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins,
      and nucleic acids that contribute to intercellular communication. ENVs have
      emerged as biomarkers and therapeutic targets but they have also been explored as
      drug delivery vehicles. However, for the latter application, clinical translation
      has been limited by low yield and inadequate targeting effects. ENV vectors with
      desired targeting properties can be produced from parental cells engineered to
      express membrane-bound targeting ligands, or they can be generated by fusion with
      targeting liposomes; however, neither approach has met clinical requirements. In
      this study, we demonstrate that mechanical extrusion of approximately 107 cells
      grafted with lipidated ligands can generate cancer cell-targeting ENV and can be
      prepared in approximately 1 hour. This rapid and economic approach could pave the
      way for clinical implementation in the future.Significance: A new and rapid
      method for production of drug-targeting nanovesicles has implications for cancer
      treatment by chimeric antigen receptor T cells and other therapies. Cancer Res;
      78(3); 798-808. (c)2017 AACR.

PMID- 29217762
TI  - SIRT6 Is a Target of Regulation by UBE3A That Contributes to Liver Tumorigenesis
      in an ANXA2-Dependent Manner.
AB  - UBE3A is an E3 ubiquitin ligase well known for its role in the proteasomal
      degradation of p53 in human papillomavirus (HPV)-associated cancers. Here we
      report that UBE3A ubiquitylates and triggers degradation of the tumor-suppressive
      sirtuin SIRT6 in hepatocellular carcinoma. UBE3A ubiquitylated the highly
      conserved Lys160 residue on SIRT6. FOXO1-mediated transcriptional repression of
      UBE3A was sufficient to stabilize SIRT6 and to epigenetically repress ANXA2, a
      key mediator of UBE3A oncogenic function. Thus, UBE3A-mediated SIRT6 degradation
      promoted the proliferative capacity, migration potential, and invasiveness of
      cells. In mouse models of hepatocellular carcinoma, SIRT6 downregulation and
      consequent induction of ANXA2 were critical for UBE3A-mediated tumorigenesis.
      Furthermore, in clinical specimens, increased UBE3A levels correlated with
      reduced SIRT6 levels and elevated ANXA2 levels in increasing tumor grades.
      Overall, our findings show how the tumor suppressor SIRT6 is regulated in
      hepatocellular carcinoma and establish the mechanism underlying UBE3A-mediated
      tumorigenesis in this disease.Significance: These findings provide mechanistic
      insights into regulation of the tumor suppressive sirtuin SIRT6 and its
      implications for the development of hepatocellular carcinoma. Cancer Res; 78(3);
      645-58. (c)2017 AACR.

PMID- 29217763
TI  - Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates
      Increases Anticancer Efficacy and Host Survival.
AB  - Current antibody-drug conjugates (ADC) have made advances in engineering the
      antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody
      ratio (DAR). However, the relationship between heterogeneous intratumoral
      distribution and efficacy of ADCs is poorly understood. Here, we compared
      trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC
      tumor distribution on efficacy. In a mouse xenograft model insensitive to
      trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1
      and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice
      the improvement in median survival compared with T-DM1 alone. In this setting,
      the effective DAR was lowered, decreasing the amount of payload delivered to each
      targeted cell but increasing the number of cells that received payload. This
      result is counterintuitive because trastuzumab acts as an antagonist in vitro and
      has no single-agent efficacy in vivo, yet improves the effectiveness of T-DM1 in
      vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and
      metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded
      the minimum required for efficacy in this model. In addition, this technique
      characterized cellular pharmacokinetics with heterogeneous delivery after 1 day,
      degradation and payload release by 2 days, and in vitro cell killing and in vivo
      tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral
      distribution of ADC, independent of payload dose or plasma clearance, plays a
      major role in ADC efficacy.Significance: This study shows how lowering the drug
      to-antibody ratio during treatment can improve the intratumoral distribution of a
      antibody-drug conjugate, with implications for improving the efficacy of this
      class of cancer drugs. Cancer Res; 78(3); 758-68. (c)2017 AACR.

PMID- 29217764
TI  - Radiotherapy-Activated Cancer-Associated Fibroblasts Promote Tumor Progression
      through Paracrine IGF1R Activation.
AB  - Preoperative radiotherapy (RT) is a mainstay in the management of rectal cancer,
      a tumor characterized by desmoplastic stroma containing cancer-associated
      fibroblasts (CAF). Although CAFs are abundantly present, the effects of RT to CAF
      and its impact on cancer cells are unknown. We evaluated the damage responses of
      CAF to RT and investigated changes in colorectal cancer cell growth,
      transcriptome, metabolome, and kinome in response to paracrine signals emerging
      from irradiated CAF. RT to CAF induced DNA damage, p53 activation, cell-cycle
      arrest, and secretion of paracrine mediators, including insulin-like growth
      factor-1 (IGF1). Subsequently, RT-activated CAFs promoted survival of colorectal
      cancer cells, as well as a metabolic switch favoring glutamine consumption
      through IGF1 receptor (IGF1R) activation. RT followed by IGF1R neutralization in
      orthotopic colorectal cancer models reduced the number of mice with organ
      metastases. Activation of the downstream IGF1R mediator mTOR was significantly
      higher in matched (intrapatient) samples and in unmatched (interpatient) samples
      from rectal cancer patients after neoadjuvant chemoradiotherapy. Taken together,
      our data support the notion that paracrine IGF1/IGF1R signaling initiated by RT
      activated CAF worsens colorectal cancer progression, establishing a preclinical
      rationale to target this activation loop to further improve clinical responses
      and patient survival.Significance: These findings reveal that paracrine
      IGF1/IGF1R signaling promotes colorectal cancer progression, establishing a
      preclinical rationale to target this activation loop. Cancer Res; 78(3); 659-70.
      (c)2017 AACR.

PMID- 29217765
TI  - Zoonotic potential of Salmonella enterica carried by pet tortoises.
AB  - The prevalence of Salmonella in chelonians is not known in the UK and it is not
      clear whether such Salmonella strains would be pathogenic for human beings. Some
      strains, such as members of the Arizonae subgroup, may be unable to cause
      anything more than very mild disease. To determine the carriage of Salmonella in
      pet tortoises, cloacal swabs were taken for culture. Salmonella enterica Group D
      was isolated from 5 of the 89 samples. All five were from the same household of
      seven tortoises. Salmonella isolates were shown by PCR to carry the invA and spiC
      genes associated with pathogenicity islands 1 and 2. Each isolate carried both
      genes indicating they had the genetic basis for disease and enterocyte invasion
      in human beings. The study indicates a low rate of asymptomatic carriage among
      the general population of pet tortoises. However, it does suggest that those
      Salmonella strains colonising the tortoise can carry Salmonellapathogenicity
      island (SPI)-1 and SPI-2 conferring the potential to cause disease in human
      beings and other animals.

PMID- 29217766
TI  - Ultrasonographic scoring system for superficial digital flexor tendon injuries in
      horses: intra- and inter-rater variability.
AB  - Superficial digital flexor tendon (SDFT) tendinopathy is an important
      musculoskeletal problem in horses. The study objective was to validate an
      ultrasonographic scoring system for SDFT injuries. Ultrasonographic images from
      14 Thoroughbred racehorses with SDFT lesions (seven core; seven diffuse) and two
      controls were blindly assessed by five clinicians on two occasions.
      Ultrasonographic parameters evaluated were: type and extent of the injury,
      location, echogenicity, cross-sectional area and longitudinal fibre pattern of
      the maximal injury zone (MIZ). Inter-rater variability and intra-rater
      reliability were assessed using Kendall's coefficient of concordance (KC) and
      Lin's concordance correlation coefficient (LC), respectively. Type of injury
      (core vs. diffuse) had perfect inter/intra-rater agreement. Cases with core
      lesions had very strong inter-rater agreement (KC >=0.74, P<0.001) and intra
      rater reliability (LC >=0.73) for all parameters apart from echogenicity. Cases
      with diffuse lesions had strong inter-rater agreement (KC >=0.62) for all
      parameters, but weak agreement for echogenicity (KC=0.22); intra-rater
      reliability was excellent for MIZ location and fibre pattern (LC >=0.82), and
      moderate (LC >=0.58) for cross-sectional area and number of zones affected. This
      scoring system was reliable and repeatable for all parameters, except for
      echogenicity. A validated scoring system will facilitate reliable recording of
      SDFT injuries and inter-study meta-analyses.

PMID- 29217767
TI  - Hypothetical route of the introduction of Schmallenberg virus into Ireland using
      two complementary analyses.
AB  - Ireland lost its official freedom from Schmallenberg virus (SBV) in October 2012.
      The route of introduction is uncertain, with long-distance displacement of
      infected Culicoides, biting midges, by suitable wind flows considered to be the
      most likely source. The authors investigated the potential introduction of SBV
      into Ireland through a Culicoides incursion event in the summer of 2012. They
      conducted SBV serology on archived bovine sera to identify the prospective
      dispersal window, then used atmospheric dispersion modelling during periods
      around this window to identify environmental conditions the authors considered
      suitable for atmospheric dispersal of Culicoides from potential infected source
      locations across Southern England. The authors believe that there was one
      plausible window over the summer of 2012, on August 10-11, based on suitable
      meteorological conditions. They conclude that a potential long-range
      transportation event of Culicoides appears to have occurred successfully only
      once during the 2012 vector competent season. If these incursion events remain at
      a low frequency, meteorological modelling has the potential to contribute cost
      effectively to the alert and response systems for vectorborne diseases in the
      future.

PMID- 29217768
TI  - Potential risk posed by the importation of ticks into the UK on animals: records
      from the Tick Surveillance Scheme.
AB  - In order to monitor important tick vectors in the UK, Public Health England's
      Tick Surveillance Scheme (TSS) receives specimens from across the country for
      identification. In recent years, an increasing number of these specimens have
      been removed from animals with a recent history of travel outside the UK. This
      paper presents all data collated by the TSS on ticks entering the country on
      recently travelled or imported animals since surveillance commenced in 2005. Ten
      different tick species representing six different genera were identified,
      entering the UK from 15 different countries. Key themes appear to be emerging
      from the last 10 years of data, including canine travel from Cyprus and Spain
      being associated with Rhipicephalus sanguineus importation, and canine travel
      from France being associated with the importation of multiple tick species and
      canine illness. In addition, more unusual importation routes have been uncovered,
      such as the importation of Hyalomma lusitanicum on a dog. Some companion animal
      owners may not be fully aware of the risks associated with ticks, and may not
      seek advice from a veterinarian before travel or importing a pet. Promoting
      awareness of ticks and tickborne disease risk during and after travel or animal
      importation is needed and veterinarians play an importation role in disseminating
      this information to their clients.

PMID- 29217769
TI  - Structural insights into ankyrin repeat-mediated recognition of the kinesin motor
      protein KIF21A by KANK1, a scaffold protein in focal adhesion.
AB  - Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of
      scaffold proteins, playing critical roles in cytoskeleton organization, cell
      polarity, and migration. Mutations in KANK proteins are implicated in cancers and
      genetic diseases, such as nephrotic syndrome. KANK proteins can bind various
      target proteins through different protein regions, including a highly conserved
      ankyrin repeat domain (ANKRD). However, the molecular basis for target
      recognition by the ANKRD remains elusive. In this study, we solved a high
      resolution crystal structure of the ANKRD of KANK1 in complex with a short
      sequence of the motor protein kinesin family member 21A (KIF21A), revealing that
      the highly specific target-binding mode of the ANKRD involves combinatorial use
      of two interfaces. Mutations in either interface disrupted the KANK1-KIF21A
      interaction. Cellular immunofluorescence localization analysis indicated that
      binding-deficient mutations block recruitment of KIF21A to focal adhesions by
      KANK1. In conclusion, our structural study provides mechanistic explanations for
      the ANKRD-mediated recognition of KIF21A and for many disease-related mutations
      identified in human KANK proteins.

PMID- 29217770
TI  - Protein C receptor stimulates multiple signaling pathways in breast cancer cells.
AB  - The protein C receptor (PROCR) has emerged as a stem cell marker in several
      normal tissues and has also been implicated in tumor progression. However, the
      functional role of PROCR and the signaling mechanisms downstream of PROCR remain
      poorly understood. Here, we dissected the PROCR signaling pathways in breast
      cancer cells. Combining protein array, knockdown, and overexpression methods, we
      found that PROCR concomitantly activates multiple pathways. We also noted that
      PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src
      kinase and transactivation of insulin-like growth factor 1 receptor (IGF-1R).
      These pathway activities led to the accumulation of c-Myc and cyclin D1. On the
      other hand, PROCR-dependent RhoA-ROCK-p38 signaling relied on coagulation factor
      II thrombin receptor (F2R). We confirmed these findings in primary cells isolated
      from triple-negative breast cancer-derived xenografts (PDX) that have high
      expression of PROCR. To the best our knowledge, this is the first comprehensive
      study of PROCR signaling in breast cancer cells, and its findings also shed light
      on the molecular mechanisms of PROCR in stem cells in normal tissue.

PMID- 29217771
TI  - RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.
AB  - It has been long assumed that post-mitotic neurons only utilize the error-prone
      non-homologous end-joining pathway to repair double-strand breaks (DSBs)
      associated with oxidative damage to DNA, given the inability of non-replicating
      neuronal DNA to utilize a sister chromatid template in the less error-prone
      homologous recombination (HR) repair pathway. However, we and others have found
      recently that active transcription triggers a replication-independent
      recombinational repair mechanism in G0/G1 phase of the cell cycle. Here we
      observed that the HR repair protein RAD52 is recruited to sites of DNA DSBs in
      terminally differentiated, post-mitotic neurons. This recruitment is dependent on
      the presence of a nascent mRNA generated during active transcription, providing
      evidence that an RNA-templated HR repair mechanism exists in non-dividing,
      terminally differentiated neurons. This recruitment of RAD52 in neurons is
      decreased by transcription inhibition. Importantly, we found that high
      concentrations of amyloid beta, a toxic protein associated with Alzheimer's
      disease, inhibits the expression and DNA damage response of RAD52, potentially
      leading to a defect in the error-free, RNA-templated HR repair mechanism. This
      study shows a novel RNA-dependent repair mechanism of DSBs in post-mitotic
      neurons and demonstrates that defects in this pathway may contribute to neuronal
      genomic instability and consequent neurodegenerative phenotypes such as those
      seen in Alzheimer's disease.

PMID- 29217772
TI  - The intracellular immune receptor Rx1 regulates the DNA-binding activity of a
      Golden2-like transcription factor.
AB  - Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable the immune
      system to recognize and respond to pathogen attack. An early consequence of
      immune activation is transcriptional reprogramming, and some NLRs have been shown
      to act in the nucleus and interact with transcription factors. The Rx1 NLR
      protein of potato is further able to bind and distort double-stranded DNA.
      However, Rx1 host targets that support a role for Rx1 in transcriptional
      reprogramming at DNA are unknown. Here, we report a functional interaction
      between Rx1 and NbGlk1, a Golden2-like transcription factor. Rx1 binds to NbGlk1
      in vitro and in planta. NbGlk1 binds to known Golden2-like consensus DNA
      sequences. Rx1 reduces the binding affinity of NbGlk1 for DNA in vitro. NbGlk1
      activates cellular responses to potato virus X, whereas Rx1 associates with
      NbGlk1 and prevents its assembly on DNA in planta unless activated by PVX. This
      study provides new mechanistic insight into how an NLR can coordinate an immune
      signaling response at DNA following pathogen perceptions.

PMID- 29217773
TI  - A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine
      phosphatase PTP1B improves insulin and leptin signaling in animal models.
AB  - The protein-tyrosine phosphatase PTP1B is a negative regulator of insulin and
      leptin signaling and a highly validated therapeutic target for diabetes and
      obesity. Conventional approaches to drug development have produced potent and
      specific PTP1B inhibitors, but these inhibitors lack oral bioavailability, which
      limits their potential for drug development. Here, we report that DPM-1001, an
      analog of the specific PTP1B inhibitor trodusquemine (MSI-1436), is a potent,
      specific, and orally bioavailable inhibitor of PTP1B. DPM-1001 also chelates
      copper, which enhanced its potency as a PTP1B inhibitor. DPM-1001 displayed anti
      diabetic properties that were associated with enhanced signaling through insulin
      and leptin receptors in animal models of diet-induced obesity. Therefore, DPM
      1001 represents a proof of concept for a new approach to therapeutic intervention
      in diabetes and obesity. Although the PTPs have been considered undruggable, the
      findings of this study suggest that allosteric PTP inhibitors may help
      reinvigorate drug development efforts that focus on this important family of
      signal-transducing enzymes.

PMID- 29217775
TI  - Chemotherapy-induced differential cell cycle arrest in B-cell lymphomas affects
      their sensitivity to Wee1 inhibition.
AB  - Chemotherapeutic agents, e.g., cytarabine and doxorubicin, cause DNA damage.
      However, it remains unknown whether such agents differentially regulate cell
      cycle arrest in distinct types of B-cell lymphomas, and whether this phenotype
      can be exploited for developing new therapies. We treated various types of B
      cells, including primary and B lymphoma cells, with cytarabine or doxorubicin,
      and determined DNA damage responses, cell cycle regulation and sensitivity to a
      Wee1 inhibitor. We found that cyclin A2/B1 upregulation appears to be an
      intrinsic programmed response to DNA damage; however, different types of B cells
      arrest in distinct phases of the cell cycle. The Wee1 inhibitor significantly
      enhanced the apoptosis of G2 phase-arrested B-cell lymphomas by inducing
      premature entry into mitosis and mitotic catastrophe, whereas it did not affect
      G1/S-phase-arrested lymphomas. Cytarabine-induced G1-arrest can be converted to
      G2-arrest by doxorubicin treatment in certain B-cell lymphomas, which correlates
      with newly acquired sensitivity to the Wee1 inhibitor. Consequently, the Wee1
      inhibitor together with cytarabine or doxorubicin inhibited tumor growth in vitro
      and in vivo more effectively, providing a potential new therapy for treating B
      cell lymphomas. We propose that the differential cell cycle arrest can be
      exploited to enhance the chemosensitivity of B-cell lymphomas.

PMID- 29217774
TI  - Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute
      myeloid leukemia.
AB  - Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic
      miRNAs. Although multiple direct targets of miR-155 have been identified, it is
      not clear how it contributes to the pathogenesis of acute myeloid leukemia. We
      found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute
      myeloid leukemia. The additional overexpression of miR-155 accelerated the
      formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in
      vivo However, in the absence or following the removal of miR-155, leukemia onset
      and progression were unaffected. Although miR-155 accelerated growth and homing
      in addition to impairing differentiation, our data underscore the
      pathophysiological relevance of miR-155 as an accelerator rather than a driver of
      leukemogenesis. This further highlights the complexity of the oncogenic program
      of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These
      findings are highly relevant to current and developing approaches for targeting
      miR-155 in acute myeloid leukemia.

PMID- 29217777
TI  - High throughput sequencing in acute lymphoblastic leukemia reveals clonal
      architecture of central nervous system and bone marrow compartments.

PMID- 29217776
TI  - Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma:
      results from the Collaboration to Collect Autologous Transplant Outcomes in
      Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies
      Working Party.
AB  - Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous
      hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140
      mg/m2 is often used in clinical practice in patients perceived to be at risk of
      excess toxicity. To determine whether melphalan 200 mg/m2 and melphalan 140 mg/m2
      are equally effective and tolerable in clinically relevant patient subgroups we
      analyzed 1964 first single autologous transplantation episodes using a series of
      Cox proportional-hazards models. Overall survival, progression-free survival,
      cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery
      and second primary malignancy rates were not significantly different between the
      melphalan 140 mg/m2 (n=245) and melphalan 200 mg/m2 (n=1719) groups.
      Multivariable subgroup analysis showed that disease status at transplantation
      interacted with overall survival, progression-free survival, and cumulative
      incidence of relapse, with a significant advantage associated with melphalan 200
      mg/m2 in patients transplanted in less than partial response (adjusted hazard
      ratios for melphalan 200 mg/m2versus melphalan 140 mg/m2: 0.5, 0.54, and 0.56).
      In contrast, transplantation in very good partial or complete response
      significantly favored melphalan 140 mg/m2 for overall survival (adjusted hazard
      ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender,
      or Karnofsky score did not interact with overall/progression-free survival or
      relapse rate in the melphalan dose groups. There were no significant survival or
      relapse rate differences between melphalan 200 mg/m2 and melphalan 140 mg/m2
      patients with high-risk or standard-risk chromosomal abnormalities. In
      conclusion, remission status at the time of transplantation may favor the use of
      melphalan 200 mg/m2 or melphalan 140 mg/m2 for key transplant outcomes
      (NCT01362972).

PMID- 29217778
TI  - Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and
      transient monosomy 7.
AB  - Familial myelodysplastic syndromes arise from haploinsufficiency of genes
      involved in hematopoiesis and are primarily associated with early-onset disease.
      Here we describe a familial syndrome in seven patients from four unrelated
      pedigrees presenting with myelodysplastic syndrome and loss of chromosome 7/7q.
      Their median age at diagnosis was 2.1 years (range, 1-42). All patients presented
      with thrombocytopenia with or without additional cytopenias and a hypocellular
      marrow without an increase of blasts. Genomic studies identified constitutional
      mutations (p.H880Q, p.R986H, p.R986C and p.V1512M) in the SAMD9L gene on 7q21,
      with decreased allele frequency in hematopoiesis. The non-random loss of mutated
      SAMD9L alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired
      truncating SAMD9L variants p.R1188X and p.S1317RfsX21. Incomplete penetrance was
      noted in 30% (3/10) of mutation carriers. Long-term observation revealed
      divergent outcomes with either progression to leukemia and/or accumulation of
      driver mutations (n=2), persistent monosomy 7 (n=4), and transient monosomy 7
      followed by spontaneous recovery with SAMD9L-wildtype UPD7q (n=2). Dysmorphic
      features or neurological symptoms were absent in our patients, pointing to the
      notion that myelodysplasia with monosomy 7 can be a sole manifestation of SAMD9L
      disease. Collectively, our results define a new subtype of familial
      myelodysplastic syndrome and provide an explanation for the phenomenon of
      transient monosomy 7. Registered at: www.clinicaltrials.gov; #NCT00047268.

PMID- 29217779
TI  - Prognostic significance of tumor burden assessed by whole-body magnetic resonance
      imaging in multiple myeloma patients treated with allogeneic stem cell
      transplantation.
AB  - Allogeneic stem cell transplantation is a therapeutic option under dispute but
      nonetheless chosen with increasing frequency for patients suffering from multiple
      myeloma in Europe. To study possible predictors of survival, 79 patients were
      investigated using whole-body magnetic resonance imaging to assess the visible
      tumor burden before and after allogeneic stem cell transplantation. Statistical
      analysis of clinical and imaging parameters included Cox regression models and
      distribution of survival time estimates (Kaplan-Meier method). Log rank test was
      used to determine the prognostic impact of the presence of focal lesions on
      survival. A higher tumor burden according to the lesion count was associated with
      a shorter overall survival (univariable/multivariable Cox regression: 1st
      magnetic resonance imaging P=0.028/P=0.048; 2nd magnetic resonance imaging
      P=0.008/P=0.024). Focal infiltration pattern itself seemed to be an additional
      adverse prognostic factor for overall survival (2nd MRI P=0.048), although no
      definite cut-off could be defined. Kaplan-Meier estimates at 60 months of follow
      up show a significant difference (Log rank P=0.04) for overall survival rates
      between patients with focal infiltration (32%) and those without (75%). Since
      this subgroup of patients may benefit from maintenance therapy, adoptive
      immunotherapy, or local interventions, whole-body imaging is an appropriate and
      highly recommendable diagnostic approach for detection of prognostically relevant
      lesions before and after treatment.

PMID- 29217781
TI  - Benefits and pitfalls of pegylated interferon-alpha2a therapy in patients with
      myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of
      Myeloproliferative neoplasms (FIM) study.
AB  - We have previously described the safety and efficacy of pegylated interferon
      alpha2a therapy in a cohort of 62 patients with myeloproliferative neoplasm
      associated myelofibrosis followed in centers affiliated to the French Intergroup
      of Myeloproliferative neoplasms. In this study, we report their long-term
      outcomes and correlations with mutational patterns of driver and non-driver
      mutations analyzed by targeted next generation sequencing. The median age at
      diagnosis was 66 years old, the median follow-up since starting pegylated
      interferon was 58 months. At the time of analysis, 30 (48.4%) patients were alive
      including 16 still being treated with pegylated interferon. The median survival
      of patients with intermediate and high-risk prognostic Lille and dynamic
      International Prognostic Scoring System scores treated with pegylated interferon
      was increased in comparison to that of historical cohorts. In addition, overall
      survival was significantly correlated with the duration of pegylated interferon
      therapy (70 versus 30 months after 2 years of treatment, P<10-12). JAK2V617F
      allele burden was decreased by more than 50% in 58.8% of patients and two
      patients even achieved complete molecular response. Next-generation sequencing
      analyses performed in 49 patients showed that 28 (57.1%) of them carried non
      driver mutations. The presence of at least one additional mutation was associated
      with a reduction of both overall and leukemia-free survival. These findings in a
      large series of patients with myelofibrosis suggest that pegylated interferon
      therapy may provide a survival benefit for patients with intermediate- or high
      risk Lille and dynamic International Prognostic Scoring System scores. It also
      reduced the JAK2V617F allele burden in most patients. These results further
      support the use of pegylated interferon in selected patients with myelofibrosis.

PMID- 29217780
TI  - From transplant to novel cellular therapies in multiple myeloma: European Myeloma
      Network guidelines and future perspectives.
AB  - Survival of myeloma patients has greatly improved with the use of autologous stem
      cell transplantation and novel agents, such as proteasome inhibitors,
      immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and
      lenalidomide-based regimens alone, the addition of high-dose melphalan followed
      by autologous transplantation significantly improves progression-free survival,
      although an overall survival benefit was not observed in all trials. Moreover,
      follow up of recent trials is still too short to show any difference in survival.
      In the light of these findings, novel agent-based induction followed by
      autologous transplantation is considered the standard upfront treatment for
      eligible patients (level of evidence: 1A). Post-transplant consolidation and
      maintenance treatment can further improve patient outcome (1A). The availability
      of several novel agents has led to the development of multiple combination
      regimens such as salvage treatment options. In this context, the role of salvage
      autologous transplantation and allotransplant has not been extensively evaluated.
      In the case of prolonged remission after upfront autologous transplantation,
      another autologous transplantation at relapse can be considered (2B). Patients
      who experience early relapse and/or have high-risk features have a poor prognosis
      and may be considered as candidates for clinical trials that, in young and fit
      patients, may also include an allograft in combination with novel agents (2B).
      Ongoing studies are evaluating the role of novel cellular therapies, such as
      inclusion of antibody-based triplets and quadruplets, and chimeric antigen
      receptor-T cells. Despite encouraging preliminary results, longer follow up and
      larger patient numbers are needed before the clinical use of these novel
      therapies can be widely recommended.

PMID- 29217782
TI  - Rational management approach to pure red cell aplasia.
AB  - Pure red cell aplasia is an orphan disease, and as such lacks rationally
      established standard therapies. Most cases are idiopathic; a subset is antibody
      mediated. There is overlap between idiopathic cases and those with T-cell large
      granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In
      each of the aforementioned, the pathogenetic mechanisms may involve autoreactive
      cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia
      patients and analyzed their pathophysiologic features and responsiveness to
      rationally applied first-line and salvage therapies in order to propose
      diagnostic and therapeutic algorithms that may be helpful in guiding the
      management of prospective patients, 52% of whom were idiopathic, while the others
      involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia. T
      cell-mediated responses ranged between a continuum from polyclonal to monoclonal
      (as seen in large granular lymphocytic leukemia). During a median observation
      period of 40 months, patients received a median of two different therapies to
      achieve remission. Frequently used therapy included calcineurin-inhibitors with a
      steroid taper yielding a first-line overall response rate of 76% (53/70). Oral
      cyclophosphamide showed activity, albeit lower than that produced by
      cyclosporine. Intravenous immunoglobulins were effective both in parvovirus
      patients and in hypogammaglobulinemia cases. In salvage settings, alemtuzumab is
      active, particularly in large granular lymphocytic leukemia-associated cases.
      Other potentially useful salvage options include rituximab, anti-thymocyte
      globulin and bortezomib. The workup of acquired pure red cell aplasia should
      include investigations of common pathological associations. Most effective
      therapies are directed against T-cell-mediated immunity, and therapeutic choices
      need to account for associated conditions that may help in choosing alternative
      salvage agents, such as intravenous immunoglobulin, alemtuzumab and bortezomib.

PMID- 29217783
TI  - Somatic STAT3 mutations in Felty syndrome: an implication for a common
      pathogenesis with large granular lymphocyte leukemia.
AB  - Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and
      rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome
      and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3
      and STAT5B mutations were discovered in 30-40% of patients with large granular
      lymphocyte leukemia. Herein, we aimed to study whether these mutations can also
      be detected in Felty syndrome, which would imply the existence of a common
      pathogenic mechanism between these two disease entities. We collected samples and
      clinical information from 14 Felty syndrome patients who were monitored at the
      rheumatology outpatient clinic for Felty syndrome. Somatic STAT3 mutations were
      discovered in 43% (6/14) of Felty syndrome patients with deep amplicon sequencing
      targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3,
      which is a known mutational hotspot. No STAT5B mutations were found. In blood
      smears, overrepresentation of large granular lymphocytes was observed, and in the
      majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by
      flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3
      positive cells was discovered. Plasma cytokine profiling showed that ten of the
      92 assayed cytokines were elevated both in Felty syndrome and large granular
      lymphocyte leukemia, and three of these cytokines were also increased in patients
      with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations
      and STAT3 activation are as frequent in Felty syndrome as they are in large
      granular lymphocyte leukemia. Considering that the symptoms and treatment
      modalities are also similar, a unified reclassification of these two syndromes is
      warranted.

PMID- 29217784
TI  - Outcome and survival of myeloma patients diagnosed 2008-2015. Real-world data on
      4904 patients from the Swedish Myeloma Registry.
AB  - Epidemiology and outcome of myeloma are mainly reported from large university
      centers and collaborative groups, and do not represent 'real-world' patients. The
      Swedish Myeloma Registry is a prospective population-based registry documenting
      characteristics, treatment and outcome in newly diagnosed myeloma, including
      asymptomatic and localized forms, with the purpose of improving disease
      management and outcome. This report presents information on patients diagnosed
      between 2008 and 2015, including data on first-line treatment in patients
      diagnosed up to 2014, with a follow up until December 2016. We present age
      adjusted incidence, patients' characteristics at baseline, treatment, response,
      and survival. Baseline data were available with a 97% coverage in 4904 patients
      (median age 71 years, males 70 years, females 73 years; 72% were 65 years or
      older), and at 1-year follow up in 3558 patients with symptomatic disease (92% of
      patients initially reported). The age-adjusted incidence was 6.8 myeloma cases
      per 100,000 inhabitants per year. Among initially symptomatic patients (n=3988),
      77% had osteolytic lesions or compression fractures, 49% had anemia, 18% impaired
      kidney function, and 13% hypercalcemia. High-dose therapy with autologous stem
      cell transplantation was given to 77% of patients aged up to 66 years, and to 22%
      of patients aged 66-70 years. In the study period, 68% received bortezomib,
      thalidomide, and/or lenalidomide as part of the first-line treatment, rising from
      31% in 2008 to 81% in 2014. In active myeloma, the median relative survival of
      patients aged 65 years or under was 7.7 years, and 3.4 years in patients aged 66
      years and over. Patients diagnosed with myeloma in more recent years were
      associated with significantly higher rates of complete or very good partial
      remission (P<0.05), and with a significantly higher survival, with a Hazard Ratio
      (HR) of 0.84 (95%CI: 0.77-0.92; P<0.05). There was a small, but significant
      survival benefit in patients treated at university hospitals (HR 0.93; 95%CI:
      0.87-0.99; P<0.05). We report here on a near complete 'real-world' population of
      myeloma patients during an 8-year period; a period in which newer drugs were
      implemented into standard practice. The overall incidence and median age were
      both higher than in most previous studies, indicating a more complete coverage of
      older patients. Myeloma survival in Sweden is comparable to other large registry
      studies, and responses and survival improved during the study period.

PMID- 29217785
TI  - Down syndrome-like acute megakaryoblastic leukemia in a patient with Cornelia de
      Lange syndrome.

PMID- 29217786
TI  - Transvaginal mesh failure: lessons for regulation of implantable devices.

PMID- 29217787
TI  - Draft Genome Sequence of Haloparvum sedimenti Strain DYS4, the Type Species of
      the Genus Haloparvum, Isolated from a Salt Mine.
AB  - Here is the genome sequence of Haloparvum sedimenti DYS4, the type species of the
      genus Haloparvum, isolated from a salt mine. The DNA G+C content of this genome
      was 68.27 mol%. The scaffold N50 was 96,635 bp. The completely sequenced and
      annotated genome is 3,243,052 bp and contains 3,313 genes.

PMID- 29217788
TI  - Complete Genome Sequences of Two Human Parainfluenza Virus Type 3 Isolates
      Collected in Brazil.
AB  - Here, we present the complete genome sequences of two human parainfluenza virus
      type 3 (HPIV-3) isolates collected from hospitalized infants suffering from acute
      respiratory disease. These are the first complete genome sequences of HPIV-3
      originating from Brazil.

PMID- 29217789
TI  - Genome Sequences of 19 Rhodococcus erythropolis Cluster CA Phages.
AB  - We report the complete genome sequences of 19 cluster CA bacteriophages isolated
      from environmental samples using Rhodococcus erythropolis as a host. All of the
      phages are Siphoviridae, have similar genome lengths (46,314 to 46,985 bp) and
      G+C contents (58.5 to 58.8%), and share nucleotide sequence similarity.

PMID- 29217791
TI  - Full-Length Genome Sequence of a Chikungunya Virus Isolate from the 2017
      Autochthonous Outbreak, Lazio Region, Italy.
AB  - We report here the genome sequence of a human chikungunya virus isolate from the
      ongoing autochthonous outbreak in central Italy. The sequence (East-Central-South
      African lineage, Indian Ocean sublineage), which is similar to recent sequences
      from Pakistan and India, shows E1 and E2 signatures of strains whose main
      mosquito vector is Aedes aegypti, although Aedes albopictus is the vector in
      Italy.

PMID- 29217790
TI  - Genome Sequences of Mycobacteriophages Amgine, Amohnition, Bella96, Cain, DarthP,
      Hammy, Krueger, LastHope, Peanam, PhelpsODU, Phrank, SirPhilip, Slimphazie, and
      Unicorn.
AB  - We report the genome sequences of 14 cluster K mycobacteriophages isolated using
      Mycobacterium smegmatis mc2155 as host. Four are closely related to subcluster K1
      phages, and 10 are members of subcluster K6. The phage genomes span considerable
      sequence diversity, including multiple types of integrases and integration sites.

PMID- 29217792
TI  - Genome Sequence of Listeria monocytogenes Strain F4244, a 4b Serotype.
AB  - Listeria monocytogenes is an opportunistic invasive foodborne pathogen. Here, we
      performed whole-genome sequencing of L. monocytogenes strain F4244 (serotype 4b)
      using Illumina sequencing. The sequence showed 94.5% identity with strain F2365,
      serotype 4b, and 90.6% with EGD-e, serotype 1/2a.

PMID- 29217793
TI  - Draft Genome Sequence of Polyaromatic Hydrocarbon-Degrading Bacterium Bacillus
      subtilis SR1, Which Has Plant Growth-Promoting Attributes.
AB  - Bacillus subtilis SR1 is a heavy metal-resistant, polyaromatic hydrocarbon
      degrading bacterium isolated from rhizospheric soil of contaminated sites. It has
      the ability to promote plant growth and utilize benzo[a]pyrene as a carbon
      source. This study reports the characteristics of the genome of B. subtilis SR1,
      which contains one circular chromosome (4,093,698 bp).

PMID- 29217794
TI  - Draft Genome Sequence of Lactobacillus salivarius SGL 03, a Novel Potential
      Probiotic Strain.
AB  - In this work, we report the draft genome sequence of Lactobacillus salivarius SGL
      03, a novel potential probiotic strain isolated from healthy infant stools.
      Antibiotic resistance analysis revealed the presence of a tetracycline resistance
      gene without elements potentially responsible for interspecific horizontal gene
      transfer.

PMID- 29217795
TI  - Draft Genome Sequence of Pseudomonas fragi Strain DBC, Which Has the Ability To
      Degrade High-Molecular-Weight Polyaromatic Hydrocarbons.
AB  - Pseudomonas fragi strain DBC was isolated from crude oil-contaminated soil. The
      genome of P. fragi DBC is comprised of 5,072,304 bp with 54.09% GC content. Genes
      for degradation of polyaromatic hydrocarbons were found in the genome, in
      addition to genetic elements for related physiological functions such as
      chemotaxis, detoxification, and quorum sensing.

PMID- 29217796
TI  - The Completed PacBio Single-Molecule Real-Time Sequence of Methylosinus
      trichosporium Strain OB3b Reveals the Presence of a Third Large Plasmid.
AB  - Presented here is the complete genome sequence of the well-studied Rhizobiales
      methanotroph Methylosinus trichosporium strain OB3b. The assembly contains
      5,183,433 bp, corresponding to a chromosome of 4,508,832 bp and three circular
      plasmids of 285,280 bp, 209,102 bp, and 180,219 bp.

PMID- 29217797
TI  - Complete Genome Sequences of Plasmid-Bearing Campylobacter coli and Campylobacter
      jejuni Strains Isolated from Retail Chicken Liver.
AB  - Complete genome sequences of Campylobacter coli strains WA333, YF2105, BG2108,
      MG1116, and BP3183 and Campylobacter jejuni strain IF1100 isolated from retail
      chicken liver showed the presence of 1,841,551-, 1,687,232-, 1,695,638-,
      1,665,146-, 1,695,360-, and 1,744,171-bp circular chromosomes, respectively.
      These isolates also contained plasmids ranging in size from 5,209 to 55,122 bp.

PMID- 29217798
TI  - Metagenome Sequence of a Microbial Community from the Gold Mine Tailings in the
      Kuzbass Area, Russia.
AB  - The metagenome of a microbial community of the sediments from a highly acidic
      iron-rich puddle at the tailings dump of the Komsomolskaya gold mine in the
      Kuzbass area, Siberia, Russia, was sequenced. Binning of contigs yielded a near
      complete genome of the dominant bacterium, representing a novel deep lineage of
      Deltaproteobacteria.

PMID- 29217799
TI  - Draft Genome Sequence of Pseudomonas stutzeri Strain 19, an Isolate Capable of
      Efficient Degradation of Aromatic Hydrocarbons.
AB  - Pseudomonas stutzeri strain 19 is a Gram-negative bacterium capable of degrading
      aromatic hydrocarbons. The draft genome of P. stutzeri 19 is estimated to be 5.1
      Mb, containing 4,652 protein-coding genes and a G+C content of 63.3%. Multiple
      genes responsible for the degradation of aromatics are present in this strain.

PMID- 29217800
TI  - Dietary Interventions for Rare Metabolic Disorders - Now Available in India!

PMID- 29217801
TI  - Accessible Pediatric Liver Transplantation in India: A Long way to go.

PMID- 29217802
TI  - Child Sexual Abuse: Management and Prevention, and Protection of Children from
      Sexual Offences (POCSO) Act.
AB  - Child Sexual Abuse is an alarming reality and is being increasingly reportedin
      India as well as globally. Pediatricians and allied medical professionals are
      often the first point of contact with abused children and their families. They
      have a key role in detecting Child Sexual Abuse, providing immediate and long
      term care and support to the victims and their families. India has adopted the
      Protection of Children from Sexual Offences Act (POCSO) in 2012. It is a
      comprehensive law on sexual abuse, which expands the scope and range of forms of
      sexual offences, makes reporting of abuse mandatory and defines guidelines for
      the examination of victims. Pediatricians and health care professionals need to
      acquire necessary expertise for clinical evaluation of child sexual abuse, and
      its prevention, management and reporting.

PMID- 29217803
TI  - Growth Hormone Deficiency in Children: From Suspecting to Diagnosing.
AB  - Isolated Growth hormone deficiency is an important and treatable cause of short
      stature. However, it is often difficult to diagnose the condition with certainty
      due to the lack of a single robust diagnostic test. Short children, other than
      those with the classical phenotype of immature chubby facies, truncal obesity and
      micropenis in boys, or those with history of cranial lesions with known
      association with hypopituitarism, should be evaluated for growth hormone
      deficiency only after excluding the other more common conditions. These children
      typically have height markedly below that expected for their midparental height
      with low height velocity and delayed bone age. Growth hormone levels should be
      checked by provocative testing, after ensuring that the child is euthyroid, and
      after priming with sex steroids if indicated. Low levels of Insulin-like growth
      factor 1 and Insulin-like growth factor binding protein 3 and pituitary
      abnormalities on neuroimaging provide important corroborative evidence to the
      diagnosis.

PMID- 29217804
TI  - Current Perspective on Exchange Transfusion.

PMID- 29217805
TI  - Paint in the Pipe: An Unusual Foreign Body.
AB  - BACKGROUND: Foreign bodies in the airway can be a diagnostic and therapeutic
      challenge. CASE CHARACTERISTICS: 30-month-old girl with complaints of noisy and
      fast breathing following fall over a pile of sand. Sand was suctioned out by
      direct bronchoscopy. The child improved initially but condition worsened in next
      four days with marked stridor and wheeze. OBSERVATION: Imaging revealed elongated
      sharp radiodense opacity in the cervical region, suggestive of foreign body. At
      repeat bronchoscopy, paint material was removed from the airway, leading to
      recovery. MESSAGE: Paint material mixed in the sand can adhere to the walls of
      the airway, and cause persistent symptoms of obstruction.

PMID- 29217806
TI  - Synovial Arteriovenous Malformation Masquerading as Arthritis.
AB  - BACKGROUND: Synovial arteriovenous malformation is rare. CASE CHARACTERISTICS: We
      present three children with recurrent monoarthritis secondary to synovial
      arteriovenous malformation. OUTCOME: Two children underwent excision of
      arteriovenous malformation. Another child had diffuse arteriovenous malformation,
      which was inoperable. MESSAGE: Synovial arteriovenous malformations should be
      considered in the differential diagnosis of monoarthritis, especially of the
      knee.

PMID- 29217807
TI  - Therapeutic Hypothermia for Neonatal Encephalopathy in Indian Neonatal Units: A
      Survey of National Practices.
AB  - This cross-sectional web-based survey suggests that cooling therapy is offered as
      standard of care for babies with neonatal encephalopathy in 10/25 (40%) of public
      and 37/68 (51%) of private level 2 or 3 neonatal units in India. 25 (53%) used
      locally improvised cooling methods, and the cooling practices differed from
      established protocols in high-income countries.

PMID- 29217808
TI  - Spectrum of Disproportionate Short Stature at a Tertiary-care Center in Northern
      India.
AB  - Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from
      genetic clinic of Lok Nayak Hospital, Delhi were assessed in this study.
      Achondroplasia was the commonest (n=9) skeletal dysplasia; conclusive diagnosis
      was not possible in six children. Molecular confirmation of clinicoradiological
      phenotype was done in 18 of 40 cases. Genetic study of all achondroplasia cases
      revealed c. 1138 G>A, p. Gly380Arg mutation in hot spot.

PMID- 29217809
TI  - Bone Mineral Density in Cystic Fibrosis: Few Concerns.

PMID- 29217810
TI  - Bone Mineral Density in Cystic Fibrosis: Few Concerns: Authors Reply.

PMID- 29217811
TI  - Creating Health Consciousness Among Adolescent Students - An Innovative
      Initiative.

PMID- 29217813
TI  - Human Milk Banking in India: Still in Infancy.

PMID- 29217812
TI  - Quest for Doctors in a Dodoland.

PMID- 29217814
TI  - An Uncommon Cause of Stridor in a Young Infant.

PMID- 29217815
TI  - Effects of Nicotine and Tocotrienol-Rich Fraction Supplementation on Cytoskeletal
      Structures of Murine Pre-Implantation Embryos.
AB  - BACKGROUND Cytoskeletal structures, in particular actin and tubulin, provide a
      fundamental framework in all cells, including embryos. The objective of this
      study was to evaluate the effects of nicotine, which is a source of oxidative
      stress, and subsequent supplementation with Tocotrienol-rich fraction (TRF) on
      actin and tubulin of 2- and 8-cell murine embryos. MATERIAL AND METHODS Thirty
      female Balb/C mice were divided into 4 groups: Group 1 received: subcutaneous
      (sc) injection of 0.9% NaCl; Group 2 received sc injection of 3.0 nicotine mg/kg
      bw/day; Group 3 received 3.0 sc injection of nicotine mg/kg bw/day +60 mg/kg
      bw/day TRF; and Group 4 received 60 sc injection of TRF mg/kg bw/day for 7
      consecutive days. The animals were superovulated with 5 IU PMSG followed by 5 IU
      hCG 48 h later. Animals were cohabited with fertile males overnight and
      euthanized through cervical dislocation at 24 h post coitum. Embryos at the 2-
      and 8-cell stages were harvested, fixed, and stained to visualize actin and
      tubulin distributions by using CLSM. RESULTS Results showed that at 2-cell stage,
      actin intensities were significantly reduced in the nicotine group compared to
      that of the control group (p<0.001). In Group 3, the intensity of actin
      significantly increased compared to that of the nicotine group (p<0.001). At 8
      cell stage, actin intensity of the nicotine group was significantly lower than
      that of the control group (p<0.001). The intensities of actin in Group 3 were
      increased compared to that of nicotine treatment alone (p<0.001). The same trend
      was seen in tubulin at 2- and 8-cell stages. Interestingly, both actin and
      tubulin structures in the TRF-treated groups were enhanced compared to the
      control. CONCLUSIONS This study suggests that TRF prevents the deleterious
      effects of nicotine on the cytoskeletal structures of 2- and 8-cell stages of pre
      implantation mice embryos in vitro.

PMID- 29217816
TI  - Wunderlich's Syndrome, or Spontaneous Retroperitoneal Hemorrhage, in a Patient
      with Tuberous Sclerosis and Bilateral Renal Angiomyolipoma.
AB  - BACKGROUND Wunderlich's syndrome, or spontaneous non-traumatic retroperitoneal
      hemorrhage, can be a life-threatening event. Renal angiomyolipoma is a rare
      benign tumor that can occur sporadically, or in association with tuberous
      sclerosis. A case of spontaneous retroperitoneal hemorrhage in a patient with
      tuberous sclerosis and bilateral renal angiomyolipoma is presented. CASE REPORT A
      33-year-old female Caucasian patient, with a known medical history of tuberous
      sclerosis, was admitted to hospital as an emergency, with right-sided abdominal
      pain. Abdominal computed tomography (CT) imaging showed bilateral renal tumors,
      consistent with bilateral renal angiomyolipoma. The larger tumor, involving the
      enlarged right kidney (24.0 cm in length), had a diameter of 21.0 cm and was
      associated with hemoperitoneum and retroperitoneal hemorrhage, and contrast
      'blush' on CT confirmed arterial bleeding. An initial urgent exploratory
      laparotomy with renal packing was initially performed, but right nephrectomy was
      required for hemorrhage control. The patient was discharged from hospital on the
      23rd postoperative day, without further complications. CONCLUSIONS This report
      describes a case of Wunderlich's Syndrome, or spontaneous retroperitoneal
      hemorrhage, in a patient with tuberous sclerosis and bilateral renal
      angiomyolipoma, presenting as an emergency. An early diagnosis and timely
      treatment are important in cases of retroperitoneal hemorrhage to prevent life
      threatening complications.

PMID- 29217817
TI  - Acetazolamide Suppresses Multi-Drug Resistance-Related Protein 1 and P
      Glycoprotein Expression by Inhibiting Aquaporins Expression in a Mesial Temporal
      Epilepsy Rat Model.
AB  - BACKGROUND Mesial temporal epilepsy (MTLE) is the most common type of focal
      epilepsy in adults, and is often drug-resistant. This study investigated the
      effects of aquaporins (AQP) inhibitor on multi-drug-resistant protein expression
      in an MTLE rat model. MATERIAL AND METHODS The MTLE rat model was established by
      injecting pilocarpine into rats. The MTLE rats were divided into an MTLE-6 h
      group, an MTLE-12 h group, and an MTLE-24 h group, together with a normal saline
      group (NS), to examine the AQP4 expression by using Western blot assay and
      immunohistochemistry assay. The other 18 MTLE model rats were used to observe the
      effects of the AQP4 inhibitor, acetazolamide, on the multi-drug-resistant protein
      1 (MRP1) and P-glycoprotein (Pgp) by using Western blot and immunohistochemistry
      assays, respectively. RESULTS AQP4 expression was enhanced in hippocampal tissues
      of MTLE model rats compared to NS rats (P<0.05). More positively stained AQP4 was
      discovered in hippocampal tissues of MTLE model rats. AQP4 inhibitor
      significantly decreased multi-drug-resistant protein MRP1 and Pgp expression in
      the AQP4 inhibitor Interfere group and the AQP4 inhibitor Therapy group compared
      to the TMLE model group (P<0.05). CONCLUSIONS The present findings confirm that
      the AQP4 inhibitor, acetazolamide, effectively inhibits the multi-drug-resistant
      protein, MRP1, and Pgp, in the MTLE rat model.

PMID- 29217818
TI  - Proteomic Analysis of Perfusate from Machine Cold Perfusion of Transplant
      Kidneys: Insights Into Protection from Injury.
AB  - BACKGROUND Machine cold perfusion is beneficial to the preservation of kidneys
      for transplantation. At the end of preservation, the perfusion solution contains
      many proteins. Using a proteomics approach, we searched for useful biomarkers and
      potential therapeutic targets in the perfusate. Our program is unique in that all
      transplant kidneys (even living donor kidneys, LKD) are placed on machine cold
      perfusion prior to transplantation. MATERIAL AND METHODS Perfusates from donation
      after neurological and circulatory determination of death (DNDD and DCDD
      respectively) and LKD were collected (n=41) and analyzed for LDH, neutrophil
      gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-2 (MMP-2) as
      markers of injury. Perfusate from each kidney was subjected to 2-dimensional gel
      electrophoresis, then analyzed using software to identify those spots which are
      significantly different between the 3 groups. Mass spectrometry was used to
      identify the proteins and their identity was confirmed with Western blot. RESULTS
      The highest levels of MMP-2, LDH, and NGAL were seen for the DCDD kidneys,
      followed by the DNDD kidneys and then LDK. Peroxiredoxin-2, NGAL, and alpha-1
      antitrypsin were identified as significantly different between the different
      types of donor kidneys, and their role and possible therapeutic strategies are
      discussed. Collagen fragments, albumin, and immunoglobulin were also identified
      as possible byproducts of the injury and may be useful is assessing the degree of
      injury. CONCLUSIONS Comparison of the perfusates from the different types of
      kidneys has allowed us to identify proteins that will be useful in future
      research into reducing injury in transplant kidneys.

PMID- 29217819
TI  - Association between serum neuron-specific enolase, age, overweight, and
      structural MRI patterns in 901 subjects.
AB  - : Serum neuron-specific enolase (sNSE) is considered a marker for neuronal
      damage, related to gray matter structures. Previous studies indicated its
      potential as marker for structural and functional damage in conditions with
      adverse effects to the brain like obesity and dementia. In the present study, we
      investigated the putative association between sNSE levels, body mass index (BMI),
      total gray matter volume (GMV), and magnetic resonance imaging-based indices of
      aging as well as Alzheimer's disease (AD)-like patterns. SUBJECTS/METHODS: sNSE
      was determined in 901 subjects (499 women, 22-81 years, BMI 18-48 kg/m2),
      participating in a population-based study (SHIP-TREND). We report age-specific
      patterns of sNSE levels between males and females. Females showed augmenting,
      males decreasing sNSE levels associated with age (males: p = 0.1052, females: p =
      0.0363). sNSE levels and BMI were non-linearly associated, showing a parabolic
      association and decreasing sNSE levels at BMI values >25 (p = 0.0056). In
      contrast to our hypotheses, sNSE levels were not associated with total GMV,
      aging, or AD-like patterns. Pathomechanisms discussed are: sex-specific hormonal
      differences, neuronal damage/differentiation, or impaired cerebral glucose
      metabolism. We assume a sex-dependence of age-related effects to the brain.
      Further, we propose in accordance to previous studies an actual neuronal damage
      in the early stages of obesity. However, with progression of overweight, we
      assume more profound effects of excess body fat to the brain.

PMID- 29217820
TI  - Longitudinal exome-wide association study to identify genetic susceptibility loci
      for hypertension in a Japanese population.
AB  - Genome-wide association studies have identified various genetic variants
      associated with complex disorders. However, these studies have commonly been
      conducted in a cross-sectional manner. Therefore, we performed a longitudinal
      exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify
      genetic variants that confer susceptibility to hypertension using ~244 000 single
      nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals
      who underwent annual health check-ups for several years. After quality control,
      the association of hypertension with SNVs was tested using a generalized
      estimating equation model. Finally, our longitudinal EWAS detected seven
      hypertension-related SNVs that passed strict criteria. Among these variants, six
      SNVs were densely located at 12q24.1, and an East Asian-specific motif
      (haplotype) 'CAAAA' comprising five derived alleles was identified. Statistical
      analyses showed that the prevalence of hypertension in individuals with the East
      Asian-specific haplotype was significantly lower than that in individuals with
      the common haplotype 'TGGGT'. Furthermore, individuals with the East Asian
      haplotype may be less susceptible to the adverse effects of smoking on
      hypertension. The longitudinal EWAS for the recessive model showed that a novel
      SNV, rs11917356 of COL6A5, was significantly associated with systolic blood
      pressure, and the derived allele at the SNV may have spread throughout East Asia
      in recent evolutionary time.

PMID- 29217821
TI  - IL-11 promotes the treatment efficacy of hematopoietic stem cell transplant
      therapy in aplastic anemia model mice through a NF-kappaB/microRNA
      204/thrombopoietin regulatory axis.
AB  - Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for
      aplastic anemia (AA) patients, and immunosuppressants may facilitate the
      efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11)
      has a thrombopoietic effect, its use in cases of chronic bone marrow failure,
      such as AA, has been proposed to induce HSC function. However, the putative
      mechanisms that may support this process remain poorly defined. We found that
      decreased miR-204-5p levels were coincident with increased proliferation in mouse
      HSCs following exposure to IL-11 in vitro. Through inhibiting NF-kB activity, miR
      204-5p repression was demonstrated to be a downstream effect of IL-11 signaling.
      miR-204-5p was shown to directly target thrombopoietin (TPO) via sequence
      dependent 3'-UTR repression, indicating that this microRNA-dependent pathway
      could serve an essential role in supporting IL-11 functions in HSCs. Increased
      TPO expression in HSCs following IL-11 exposure could be mimicked or blocked by
      inhibiting or overexpressing miR-204-5p, respectively. Consistent with these in
      vitro findings, IL-11 promoted HSC engraftment in a mouse model of AA, an effect
      that was attenuated in cells overexpressing miR-204-5p. The reduction in miR-204
      5p levels is an integral component of IL-11 signaling that may play an essential
      role in treating AA.

PMID- 29217822
TI  - Hepatocyte toll-like receptor 4 mediates lipopolysaccharide-induced hepcidin
      expression.
AB  - Hepcidin expression is induced by inflammatory molecules such as
      lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes
      directly respond to LPS, the molecular mechanism underlying toll-like receptor
      (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we
      show that LPS can directly induce the mRNA expression and secretion of hepcidin
      by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid
      differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing
      interferon-beta (TRIF), we demonstrated that LPS-induced hepcidin expression by
      hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent
      signaling pathway. Hepcidin promoter activity was significantly increased by
      MyD88-dependent downstream signaling molecules (interleukin-1 receptor-associated
      kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6),
      which activate c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). We
      then confirmed that LPS stimulation induced the phosphorylation of JNK and c-Jun,
      and observed strong occupancy of the hepcidin promoter by c-Jun. Promoter
      mutation analysis also identified the AP-1-binding site on the hepcidin promoter.
      Finally, bone marrow transplantation between wild-type and TLR4 knockout mice
      revealed that hepatic TLR4-dependent hepcidin expression was comparable to
      macrophage TLR4-dependent hepcidin expression induced by LPS. Taken together,
      these results suggest that TLR4 expressed by hepatocytes regulates hepcidin
      expression via the IRAK-TRAF6-JNK-AP-1 axis.

PMID- 29217823
TI  - Lysophosphatidic acid protects against acetaminophen-induced acute liver injury.
AB  - We investigated the effect of lysophosphatidic acid (LPA) in experimental
      acetaminophen (APAP)-induced acute liver injury. LPA administration significantly
      reduced APAP-challenged acute liver injury, showing attenuated liver damage,
      liver cell death and aspartate aminotransferase and alanine aminotransferase
      levels. APAP overdose-induced mortality was also significantly decreased by LPA
      administration. Regarding the mechanism involved in LPA-induced protection
      against acute liver injury, LPA administration significantly increased the
      glutathione level, which was markedly decreased in APAP challenge-induced acute
      liver injury. LPA administration also strongly blocked the APAP challenge
      elicited phosphorylation of JNK, ERK and GSK3beta, which are involved in the
      pathogenesis of acute liver injury. Furthermore, LPA administration decreased the
      production of TNF-alpha and IL-1beta in an experimental drug-induced liver injury
      animal model. Mouse primary hepatocytes express LPA1,3-6, and injection of the
      LPA receptor antagonist KI16425 (an LPA1,3-selective inhibitor) or H2L 5765834
      (an LPA1,3,5-selective inhibitor) did not reverse the LPA-induced protective
      effects against acute liver injury. The therapeutic administration of LPA also
      blocked APAP-induced liver damage, leading to an increased survival rate.
      Collectively, these results indicate that the well-known bioactive lipid LPA can
      block the pathogenesis of APAP-induced acute liver injury by increasing the
      glutathione level but decreasing inflammatory cytokines in an LPA1,3,5
      independent manner. Our results suggest that LPA might be an important
      therapeutic agent for drug-induced liver injury.

PMID- 29217825
TI  - Prion disease: Skin is a source of infectious prions in sCJD.

PMID- 29217826
TI  - Parkinson's disease - the story of an eponym.
AB  - One of the most prevalent neurodegenerative diseases worldwide is still referred
      to as 'Parkinson's disease'. The condition is named after James Parkinson who, in
      1817, described the shaking palsy (paralysis agitans). In the bicentennial year
      of this publication, we trace when and why the shaking palsy became Parkinson's
      disease. The term was coined by William Rutherford Sanders of Edinburgh in 1865
      and later entered general usage through the influence of Jean-Martin Charcot and
      the school that he nurtured at the Salpetriere Hospital in Paris. Despite a move
      towards more mechanism-based nosology for many medical conditions in recent
      years, the Parkinson's disease eponym remains in place, celebrating the life and
      work of this doctor, palaeontologist and political activist.

PMID- 29217824
TI  - Soluble Tau has devastating effects on the structural plasticity of hippocampal
      granule neurons.
AB  - Tau is a neuronal microtubule-associated protein with countless physiological
      functions. Although the detrimental effects of insoluble aggregated Tau have been
      widely studied, recent evidence supports the notion that soluble Tau (composed
      mostly of monomers and dimers) is also toxic for neurons. Here we evaluated the
      long-term impact of a single stereotaxic injection of human soluble Tau on
      hippocampal granule neurons in mice. At the ultrastructural level, soluble Tau
      reduced the number of afferent synapses and caused a dramatic depletion of
      synaptic vesicles both in afferent and efferent synapses. Furthermore, the use of
      an RFP-expressing retrovirus revealed that soluble Tau altered the morphology of
      newborn granule neurons and reduced their afferent (dendritic spines) and
      efferent (mossy fiber terminals) connectivity. Finally, soluble Tau caused
      specific impairment of behavioral pattern separation capacity. Our results thus
      demonstrate for the first time that soluble Tau causes long-term detrimental
      effects on the morphology and connectivity of newborn granule neurons and that
      these effects correlate with impaired behavioral pattern separation skills. These
      data might be relevant for the field of neurodegenerative disorders, since they
      contribute to reinforcing the pathological roles played by distinct Tau species
      in vivo.

PMID- 29217828
TI  - Frequently used bioinformatics tools overestimate the damaging effect of allelic
      variants.
AB  - We selected two sets of naturally occurring human missense allelic variants
      within innate immune genes. The first set represented eleven non-synonymous
      variants in six different genes involved in interferon (IFN) induction, present
      in a cohort of patients suffering from herpes simplex encephalitis (HSE) and the
      second set represented sixteen allelic variants of the IFNLR1 gene. We recreated
      the variants in vitro and tested their effect on protein function in a HEK293T
      cell based assay. We then used an array of 14 available bioinformatics tools to
      predict the effect of these variants upon protein function. To our surprise two
      of the most commonly used tools, CADD and SIFT, produced a high rate of false
      positives, whereas SNPs&GO exhibited the lowest rate of false positives in our
      test. As the problem in our test in general was false positive variants,
      inclusion of mutation significance cutoff (MSC) did not improve accuracy.

PMID- 29217827
TI  - Genome-Wide Association Study of Male Sexual Orientation.
AB  - Family and twin studies suggest that genes play a role in male sexual
      orientation. We conducted a genome-wide association study (GWAS) of male sexual
      orientation on a primarily European ancestry sample of 1,077 homosexual men and
      1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP)
      arrays. We identified several SNPs with p < 10-5, including regions of multiple
      supporting SNPs on chromosomes 13 (minimum p = 7.5 * 10-7) and 14 (p = 4.7 * 10
      7). The genes nearest to these peaks have functions plausibly relevant to the
      development of sexual orientation. On chromosome 13, SLITRK6 is a
      neurodevelopmental gene mostly expressed in the diencephalon, which contains a
      region previously reported as differing in size in men by sexual orientation. On
      chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain
      past findings relating familial atypical thyroid function and male homosexuality.
      Furthermore, skewed X chromosome inactivation has been found in the thyroid
      condition, Graves' disease, as well as in mothers of homosexual men. On
      pericentromeric chromosome 8 within our previously reported linkage peak, we
      found support (p = 4.1 * 10-3) for a SNP association previously reported
      (rs77013977, p = 7.1 * 10-8), with the combined analysis yielding p = 6.7 * 10-9,
      i.e., a genome-wide significant association.

PMID- 29217829
TI  - Genome-wide genotyping uncovers genetic profiles and history of the Russian
      cattle breeds.
AB  - One of the most economically important areas within the Russian agricultural
      sector is dairy and beef cattle farming contributing about $11 billion to the
      Russian economy annually. Trade connections, selection and breeding have resulted
      in the establishment of a number of breeds that are presumably adapted to local
      climatic conditions. Little however is known about the ancestry and history of
      Russian native cattle. To address this question, we genotyped 274 individuals
      from 18 breeds bred in Russia and compared them to 135 additional breeds from
      around the world that had been genotyped previously. Our results suggest a shared
      ancestry between most of the Russian cattle and European taurine breeds, apart
      from a few breeds that shared ancestry with the Asian taurines. The Yakut cattle,
      belonging to the latter group, was found to be the most diverged breed in the
      whole combined dataset according to structure results. Haplotype sharing further
      suggests that the Russian cattle can be divided into four major clusters
      reflecting ancestral relations with other breeds. Herein, we therefore shed light
      on to the history of Russian cattle and identified closely related breeds to
      those from Russia. Our results will facilitate future research on detecting
      signatures of selection in cattle genomes and eventually inform future genetics
      assisted livestock breeding programs in Russia and in other countries.

PMID- 29217830
TI  - Patient-reported quality of life progression in men with prostate cancer
      following primary cryotherapy, cyberknife, or active holistic surveillance.
AB  - BACKGROUND: Technological advancements have led to the success of minimally
      invasive treatment modalities for prostate cancer such as CyberKnife and
      Cryotherapy. Here, we investigate patient-reported urinary function, bowel
      habits, and sexual function in patients following CyberKnife (CK) or Cryotherapy
      treatment, and compare them with active holistic surveillance (AHS) patients.
      METHODS: An IRB-approved institutional database was retrospectively reviewed for
      patients who underwent CK, Cryotherapy, or AHS. Quality of life (QoL) survey
      responses were collected every three months and the mean function scores were
      analyzed in yearly intervals over the 4 years post-treatment. RESULTS: 279
      patients (767 survey sets) were included in the study. There was no difference
      among groups in urinary function scores. The CyberKnife group had significantly
      lower bowel habit scores in the early years following treatment (year 2 mean
      difference: -5.4, P < 0.01) but returned to AHS level scores by year 4.
      Cryotherapy patients exhibited initially lower, but not statistically
      significant, bowel function scores, which then improved and approached those of
      AHS. Both CyberKnife (year 1 mean difference: -26.7, P < 0.001) and Cryotherapy
      groups (-35.4, P < 0.001) had early lower sexual function scores relative to AHS,
      but then gradually improved and were not significantly different from AHS by the
      third year post-treatment. A history of hormonal therapy was associated with a
      lower sexual function scores relative to those patients who did not receive
      hormones in both CyberKnife (-18.45, P < 0.01) and Cryotherapy patients (-14.6, P
      < 0.05). CONCLUSIONS: After initial lower bowel habits and sexual function
      scores, CyberKnife or Cryotherapy-treated patients had no significant difference
      in QoL relative to AHS patients. These results highlight the benefit of
      CyberKnife and Cryotherapy in the management of organ-confined prostate cancer.

PMID- 29217831
TI  - The public health impact of a new simple practical technique for collection and
      transfer of toxic jellyfish specimens and for nematocyst identification.
AB  - Our team aimed to create a new, simple, and inexpensive technique for collecting
      and transferring of toxic jellyfish specimens and for nematocysts identification.
      We collected tentacles of Chironex spp., Morbakka spp., and Physalia spp., and
      transferred them from the beaches by standard and by 'vacuum sticky tape' (VST)
      techniques. For the VST technique, our team placed the sticky tape on a tentacle
      and then folded it over to seal the tentacle in the equivalent of a vacuum. We
      kept the VST in room temperature. For nematocyst identification, we placed the
      VST on a glass microscope slide and took photographs down the microscope's eye
      piece using a mobile phone camera. The image quality was as good as when produced
      by standard techniques. Different classes of toxic jellyfish could be identified.
      Thus, VST is a potential public health breakthrough because it is practical,
      durable, inexpensive, allows good discrimination. It enables early warning of
      danger to health and rapid response via social network.

PMID- 29217832
TI  - Inter and intra-hemispheric structural imaging markers predict depression relapse
      after electroconvulsive therapy: a multisite study.
AB  - Relapse of depression following treatment is high. Biomarkers predictive of an
      individual's relapse risk could provide earlier opportunities for prevention.
      Since electroconvulsive therapy (ECT) elicits robust and rapidly acting
      antidepressant effects, but has a >50% relapse rate, ECT presents a valuable
      model for determining predictors of relapse-risk. Although previous studies have
      associated ECT-induced changes in brain morphometry with clinical response,
      longer-term outcomes have not been addressed. Using structural imaging data from
      42 ECT-responsive patients obtained prior to and directly following an ECT
      treatment index series at two independent sites (UCLA: n = 17, age = 45.41+/
      12.34 years; UNM: n = 25; age = 65.00+/-8.44), here we test relapse prediction
      within 6-months post-ECT. Random forests were used to predict subsequent relapse
      using singular and ratios of intra and inter-hemispheric structural imaging
      measures and clinical variables from pre-, post-, and pre-to-post ECT. Relapse
      risk was determined as a function of feature variation. Relapse was well
      predicted both within site and when cohorts were pooled where top-performing
      models yielded balanced accuracies of 71-78%. Top predictors included cingulate
      isthmus asymmetry, pallidal asymmetry, the ratio of the paracentral to precentral
      cortical thickness and the ratio of lateral occipital to pericalcarine cortical
      thickness. Pooling cohorts and predicting relapse from post-treatment measures
      provided the best classification performances. However, classifiers trained on
      each age-disparate cohort were less informative for prediction in the held-out
      cohort. Post-treatment structural neuroimaging measures and the ratios of
      connected regions commonly implicated in depression pathophysiology are
      informative of relapse risk. Structural imaging measures may have utility for
      devising more personalized preventative medicine approaches.

PMID- 29217833
TI  - CALR mutational status identifies different disease subtypes of essential
      thrombocythemia showing distinct expression profiles.
AB  - Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia
      negative myeloproliferative neoplasms (MPNs) characterized by erythrocytosis and
      thrombocytosis, respectively. Approximately 95% of PV and 50-70% of ET patients
      harbor the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET
      patients carry CALRins5 or CALRdel52 mutations. These ET CALR-mutated subjects
      show higher platelet count and lower thrombotic risk compared to JAK2-mutated
      patients. Here, we showed that CALR-mutated and JAK2V617F-positive CD34+ cells
      display different gene and miRNA expression profiles. Indeed, we highlighted
      several pathways differentially activated between JAK2V617F- and CALR-mutated
      progenitors, i.e., mTOR, MAPK/PI3K, and MYC pathways. Furthermore, we unveiled
      that the expression of several genes involved in DNA repair, chromatin
      remodeling, splicing, and chromatid cohesion are decreased in CALR-mutated cells.
      According to the low risk of thrombosis in CALR-mutated patients, we also found
      the downregulation of several genes involved in thrombin signaling and platelet
      activation. As a whole, these data support the model that CALR-mutated ET could
      be considered as a distinct disease entity from JAK2V617F-positive MPNs and may
      provide the molecular basis supporting the different clinical features of these
      patients.

PMID- 29217835
TI  - Bayesian prediction intervals for assessing P-value variability in prospective
      replication studies.
AB  - Increased availability of data and accessibility of computational tools in recent
      years have created an unprecedented upsurge of scientific studies driven by
      statistical analysis. Limitations inherent to statistics impose constraints on
      the reliability of conclusions drawn from data, so misuse of statistical methods
      is a growing concern. Hypothesis and significance testing, and the accompanying P
      values are being scrutinized as representing the most widely applied and abused
      practices. One line of critique is that P-values are inherently unfit to fulfill
      their ostensible role as measures of credibility for scientific hypotheses. It
      has also been suggested that while P-values may have their role as summary
      measures of effect, researchers underappreciate the degree of randomness in the P
      value. High variability of P-values would suggest that having obtained a small P
      value in one study, one is, ne vertheless, still likely to obtain a much larger P
      value in a similarly powered replication study. Thus, "replicability of P-value"
      is in itself questionable. To characterize P-value variability, one can use
      prediction intervals whose endpoints reflect the likely spread of P-values that
      could have been obtained by a replication study. Unfortunately, the intervals
      currently in use, the frequentist P-intervals, are based on unrealistic implicit
      assumptions. Namely, P-intervals are constructed with the assumptions that imply
      substantial chances of encountering large values of effect size in an
      observational study, which leads to bias. The long-run frequentist probability
      provided by P-intervals is similar in interpretation to that of the classical
      confidence intervals, but the endpoints of any particular interval lack
      interpretation as probabilistic bounds for the possible spread of future P-values
      that may have been obtained in replication studies. Along with classical
      frequentist intervals, there exists a Bayesian viewpoint toward interval
      construction in which the endpoints of an interval have a meaningful
      probabilistic interpretation. We propose Bayesian intervals for prediction of P
      value variability in prospective replication studies. Contingent upon approximate
      prior knowledge of the effect size distribution, our proposed Bayesian intervals
      have endpoints that are directly interpretable as probabilistic bounds for
      replication P-values, and they are resistant to selection bias. We showcase our
      approach by its application to P-values reported for five psychiatric disorders
      by the Psychiatric Genomics Consortium group.

PMID- 29217834
TI  - Gender-specific alteration of energy balance and circadian locomotor activity in
      the Crtc1 knockout mouse model of depression.
AB  - Obesity and depression are major public health concerns, and there is increasing
      evidence that they share etiological mechanisms. CREB-regulated transcription
      coactivator 1 (CRTC1) participates in neurobiological pathways involved in both
      mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive
      like and obese phenotype in early adulthood, and are therefore a relevant animal
      model to explore possible common mechanisms underlying mood disorders and
      obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further
      characterized by investigating CRTC1's role in the homeostatic and hedonic
      regulation of food intake, as well as its influence on daily locomotor activity.
      Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of
      energy balance. Mutant males were hyperphagic and rapidly developed obesity on
      normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity
      without hyperphagia. Overeating of mutant males was accompanied by alterations in
      the expression of several orexigenic and anorexigenic hypothalamic genes, thus
      confirming a key role of CRTC1 in the central regulation of food intake. No
      alteration in preference and conditioned response for saccharine was observed in
      Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an
      altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a
      hyperphagic behavior only during the resting (diurnal) phase of the light cycle.
      This abnormal feeding behavior was associated with a higher diurnal locomotor
      activity indicating that the lack of CRTC1 may affect circadian rhythmicity.
      Collectively, these findings highlight the male-specific involvement of CRTC1 in
      the central control of energy balance and circadian locomotor activity.

PMID- 29217836
TI  - Drug development for neurodevelopmental disorders: lessons learned from fragile X
      syndrome.
AB  - Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong
      cognitive and behavioural deficits and represent a major public health burden.
      FXS is the most frequent monogenic form of intellectual disability and autism,
      and the underlying pathophysiology linked to its causal gene, FMR1, has been the
      focus of intense research. Key alterations in synaptic function thought to
      underlie this neurodevelopmental disorder have been characterized and rescued in
      animal models of FXS using genetic and pharmacological approaches. These robust
      preclinical findings have led to the implementation of the most comprehensive
      drug development programme undertaken thus far for a genetically defined
      neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate
      receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor
      agonist. However, none of the trials has been able to unambiguously demonstrate
      efficacy, and they have also highlighted the extent of the knowledge gaps in drug
      development for FXS and other neurodevelopmental disorders. In this Review, we
      examine potential issues in the previous studies and future directions for
      preclinical and clinical trials. FXS is at the forefront of efforts to develop
      drugs for neurodevelopmental disorders, and lessons learned in the process will
      also be important for such disorders.

PMID- 29217837
TI  - Drug development in the era of precision medicine.
AB  - For the past three decades, the use of genomics to inform drug discovery and
      development pipelines has generated both excitement and scepticism. Although
      earlier efforts successfully identified some new drug targets, the overall
      clinical efficacy of developed drugs has remained unimpressive, owing in large
      part to the heterogeneous causes of disease. Recent technological and analytical
      advances in genomics, however, have now made it possible to rapidly identify and
      interpret the genetic variation underlying a single patient's disease, thereby
      providing a window into patient-specific mechanisms that cause or contribute to
      disease, which could ultimately enable the 'precise' targeting of these
      mechanisms. Here, we first examine and highlight the successes and limitations of
      the earlier phases of genomics in drug discovery and development. We then review
      the current major efforts in precision medicine and discuss the potential broader
      utility of mechanistically guided treatments going forward.

PMID- 29217839
TI  - Tumour microenvironment: Microbes matter.

PMID- 29217841
TI  - The great escape.

PMID- 29217838
TI  - An evolutionary perspective on field cancerization.
AB  - Tumorigenesis begins long before the growth of a clinically detectable lesion
      and, indeed, even before any of the usual morphological correlates of pre
      malignancy are recognizable. Field cancerization, which is the replacement of the
      normal cell population by a cancer-primed cell population that may show no
      morphological change, is now recognized to underlie the development of many types
      of cancer, including the common carcinomas of the lung, colon, skin, prostate and
      bladder. Field cancerization is the consequence of the evolution of somatic cells
      in the body that results in cells that carry some but not all phenotypes required
      for malignancy. Here, we review the evidence of field cancerization across organs
      and examine the biological mechanisms that drive the evolutionary process that
      results in field creation. We discuss the clinical implications, principally, how
      measurements of the cancerized field could improve cancer risk prediction in
      patients with pre-malignant disease.

PMID- 29217842
TI  - Microbiome: Precision engineering of gut metabolites.

PMID- 29217843
TI  - Host response: Suppressing gut feelings.

PMID- 29217840
TI  - The role of anxious distress in immune dysregulation in patients with major
      depressive disorder.
AB  - Although depression with anxious distress appears to be a clinically relevant
      subtype of major depressive disorder (MDD), whether it involves specific
      pathophysiology remains unclear. Inflammation has been implicated, but not
      comprehensively studied. We examined within a large MDD sample whether anxious
      distress and related anxiety features are associated with differential basal
      inflammation and innate cytokine production capacity. Data are from 1078 MDD
      patients from the Netherlands Study of Depression and Anxiety. In addition to the
      DSM-5 anxious distress specifier, we studied various dimensional anxiety scales
      (e.g. Inventory of Depressive Symptomatology anxiety arousal subscale [IDS-AA],
      Beck Anxiety Inventory [BAI], Mood and Anxiety Symptoms Questionnaire Anxious
      Arousal scale [MASQ-AA]). The specifier was constructed using five self-report
      items from the IDS and BAI. Basal inflammatory markers included C-reactive
      protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Innate
      production capacity was assessed by 13 lipopolysaccharide (LPS)-stimulated
      inflammatory markers. Basal and LPS-stimulated inflammation index scores were
      created. Basal inflammation was not associated with anxious distress (prevalence
      = 54.3%) in MDD patients, except for a modest positive association for BAI score.
      However, anxious distress was associated with higher LPS-stimulated levels
      (interferon-gamma, IL-6, monocyte chemotactic protein (MCP)-1, macrophage
      inflammatory protein (MIP)-1alpha, matrix metalloproteinase (MMP)-2, TNF-alpha,
      LPS-stimulated index). Other anxiety indicators (anxious distress specifier
      score, BAI, MASQ-AA) were also associated with increased innate production
      capacity. Within a large MDD sample, the anxious distress specifier was
      associated with increased innate cytokine production capacity but not with basal
      inflammation. Results from dimensional anxiety indicators largely confirm these
      results. These findings provide new insight into the pathophysiology of anxious
      depression.

PMID- 29217844
TI  - Microbiome: Fusobacterium persistence in colorectal cancer.

PMID- 29217845
TI  - Viral pathogenesis: A small change makes a big difference.

PMID- 29217846
TI  - Host response: Fungal safeguards in the gut.

PMID- 29217847
TI  - Black Lives Matter: A Call to Action for Counseling Psychology Leaders.
AB  - Police brutality and widespread systemic racism represent historical and current
      sources of trauma in Black communities. Both the Black Lives Matter movement and
      counseling psychology propose to confront these realities at multiple levels.
      Black Lives Matter seeks to increase awareness about systemic racism and promote
      resilience among Black people. Counseling psychology states values of
      multiculturalism, social justice, and advocacy. Executive leadership in
      counseling psychology may seek to promote racial justice, yet struggle with how
      to participate in Black Lives Matter movements and address racial discrimination
      within larger systems spontaneously and consistently. However, counseling
      psychology trainees and professionals are actively involved in the Black Lives
      Matter movement, leading the way forward. Through the framework of spontaneity in
      social movements, this manuscript highlights what counseling psychologists are
      currently contributing to Black Lives Matter and makes recommendations that build
      on the opportunity counseling psychologists have for further involvement in the
      movement.

PMID- 29217848
TI  - A Radio Frequency Radiation Exposure System for Rodents based on Reverberation
      Chambers.
AB  - In this paper we present the novel design features, their technical
      implementation, and an evaluation of the radio Frequency (RF) exposure systems
      developed for the National Toxicology Program (NTP) of the National Institute of
      Environmental Health Sciences (NIEHS) studies on the potential toxicity and
      carcinogenicity of 2nd and 3rd generation mobile-phone signals. The system
      requirements for this 2-year NTP cancer bioassay study were the tightly
      controlled lifetime exposure of rodents (1568 rats and 1512 mice) to three power
      levels plus sham simulating typical daily, and higher, exposures of users of GSM
      and CDMA (IS95) signals. Reverberation chambers and animal housing were designed
      to allow extended exposure time per day for free-roaming individually-housed
      animals. The performance of the chamber was characterized in terms of
      homogeneity, stirred to unstirred energy, efficiency. The achieved homogeneity
      was 0.59 dB and 0.48 dB at 900 and 1900 MHz respectively. The temporal variation
      in the electric field strength was optimized to give similar characteristics to
      that of the power control of a phone in a real network using the two stirrers.
      Experimental dosimetry was performed to validate the SAR sensitivity and
      determine the SAR uniformity throughout the exposure volume; SAR uniformities of
      0.46 dB and 0.40 dB, respectively, for rats and mice were achieved.

PMID- 29217850
TI  - Indian Society of Anaesthesiologists cardiopulmonary resuscitation guidelines:
      Ushering in a new initiative.

PMID- 29217849
TI  - Life-Time Dosimetric Assessment for Mice and Rats Exposed in Reverberation
      Chambers of the 2-Year NTP Cancer Bioassay Study on Cell Phone Radiation.
AB  - In this paper, we present the detailed life-time dosimetry analysis for rodents
      exposed in the reverberation exposure system designed for the two-year cancer
      bioassay study conducted by the National Toxicology Program of the National
      Institute of Environmental Health Sciences. The study required the well
      controlled and characterized exposure of individually housed, unrestrained mice
      at 1900 MHz and rats at 900 MHz, frequencies chosen to give best uniformity
      exposure of organs and tissues. The wbSAR, the peak spatial SAR and the organ
      specific SAR as well as the uncertainty and variation due to the exposure
      environment, differences in the growth rates, and animal posture were assessed.
      Compared to the wbSAR, the average exposure of the high-water-content tissues
      (blood, heart, lung) were higher by ~4 dB, while the low-loss tissues (bone and
      fat) were less by ~9 dB. The maximum uncertainty over the exposure period for the
      SAR was estimated to be <49% (k=2) for the rodents whereas the relative
      uncertainty between the group was <14% (k=1). The instantaneous variation
      (averaged over 1 min) was <13% (k=1), which is small compared to other long term
      exposure research projects. These detailed dosimetric results empowers comparison
      with other studies and provides a reference for studies of long-term biological
      effects of exposure of rodents to RF energy.

PMID- 29217851
TI  - Compression-only life support (COLS) for cardiopulmonary resuscitation by
      layperson outside the hospital.
AB  - The cardiopulmonary resuscitation (CPR) guidelines of compression-only life
      support (COLS) for management of the victim with cardiopulmonary arrest in adults
      provide a stepwise algorithmic approach for optimal outcome of the victim outside
      the hospital by untrained laypersons. These guidelines have been developed to
      recommend practical, uniform and acceptable resuscitation algorithms across
      India. As resuscitation data of the Indian population are inadequate, these
      guidelines have been based on international literature. The guidelines have been
      recommended after discussion among Indian experts and the recommendations
      modified to ensure its practical applicability across the country. The COLS
      emphasises on early recognition of cardiac arrest and activation, early chest
      compression and early transfer to medical facility. The guidelines emphasise
      avoidance of any interruption of chest compression, and thus relies primarily on
      chest compression-only CPR by laypersons.

PMID- 29217852
TI  - Basic cardiopulmonary life support (BCLS) for cardiopulmonary resuscitation by
      trained paramedics and medics outside the hospital.
AB  - The cardiopulmonary resuscitation guideline of Basic Cardiopulmonary Life Support
      (BCLS) for management of adult victims with cardiopulmonary arrest outside the
      hospital provides an algorithmic stepwise approach for optimal outcome of the
      victims by trained medics and paramedics. This guideline has been developed
      considering the need to have a universally acceptable practice guideline for
      India and keeping in mind the infrastructural limitations of some areas of the
      country. This guideline is based on evidence elicited in the international and
      national literature. In the absence of data from Indian population, the excerpts
      have been taken from international data, discussed with Indian experts and
      thereafter modified to make them practically applicable across India. The optimal
      outcome for a victim with cardiopulmonary arrest would depend on core links of
      early recognition and activation; early high-quality cardiopulmonary
      resuscitation, early defibrillation and early transfer to medical facility. These
      links are elaborated in a stepwise manner in the BCLS algorithm. The BCLS also
      emphasise on quality check for various steps of resuscitation.

PMID- 29217854
TI  - Need for resuscitation registry in India based on Indian Society of
      Anaesthesiologists cardiopulmonary resuscitation guidelines.

PMID- 29217853
TI  - Comprehensive cardiopulmonary life support (CCLS) for cardiopulmonary
      resuscitation by trained paramedics and medics inside the hospital.
AB  - The cardiopulmonary resuscitation (CPR) guideline of comprehensive
      cardiopulmonary life support (CCLS) for management of the patient with
      cardiopulmonary arrest in adults provides an algorithmic step-wise approach for
      optimal outcome of the patient inside the hospital by trained medics and
      paramedics. This guideline has been developed considering the infrastructure of
      healthcare delivery system in India. This is based on evidence in the
      international and national literature. In the absence of data from the Indian
      population, the extrapolation has been made from international data, discussed
      with Indian experts and modified accordingly to ensure their applicability in
      India. The CCLS guideline emphasise the need to recognise patients at risk for
      cardiac arrest and their timely management before a cardiac arrest occurs. The
      basic components of CPR include chest compressions for blood circulation; airway
      maintenance to ensure airway patency; lung ventilation to enable oxygenation and
      defibrillation to convert a pathologic 'shockable' cardiac rhythm to one capable
      to maintaining effective blood circulation. CCLS emphasises incorporation of
      airway management, drugs, and identification of the cause of arrest and its
      correction, while chest compression and ventilation are ongoing. It also
      emphasises the value of organised team approach and optimal post-resuscitation
      care.

PMID- 29217855
TI  - Effect of nasal oxygen supplementation during apnoea of intubation on arterial
      oxygen levels: A prospective randomised controlled trial.
AB  - Background and Aims: Apnoeic oxygenation during laryngoscopy has been emphasised
      in recent recommendations for airway management. We aimed to compare the effect
      of nasal oxygen supplementation on time for pulse oximeter oxygen saturation
      (SpO2) to fall from 100% to 92% (desaturation safety time), to assess the
      arterial oxygen partial pressures (PaO2) with and without nasal oxygen
      supplementation and the time for SpO2 to recover from 92% to 100% after
      initiation of ventilation. Methods: This is a prospective randomised placebo
      controlled trial involving sixty patients, where nasal oxygen supplementation
      given at 10 L/min during apnoea of laryngoscopy in one group of patients (Group
      O2) was compared to no oxygen supplementation in other group (Group NoO2).
      Desaturation safety period and the PaO2 just after intubation were compared. Time
      for SpO2 to increase to 100% after initiation of ventilation was also assessed.
      Demographic details were compared using the Chi-square and t-tests. Student's t
      test for independent variables was used to compare means of data obtained.
      Results: Desaturation safety period at 415.46 +/- 97.23 seconds in group O2
      versus 378.69 +/- 89.31 seconds in group NoO2(P = 0.213) and PaO2(P = 0.952) and
      time to recovery of SpO2 (P = 0.058) were similar in both groups. Rise in
      arterial carbon dioxide secondary to apnoea was slower in oxygen supplementation
      group (P = 0.032). Conclusion: Apnoeic oxygen supplementation at 10 L/min flow by
      nasal prong did not significantly prolong the apnoea desaturation safety periods
      or the PaO2 in our study.

PMID- 29217856
TI  - Adductor canal block for post-operative analgesia after simultaneous bilateral
      total knee replacement: A randomised controlled trial to study the effect of
      addition of dexmedetomidine to ropivacaine.
AB  - Background and Aims: Knee replacement surgery causes tremendous post-operative
      pain and adductor canal block (ACB) is used for post-operative analgesia. This is
      a randomised, controlled, three-arm parallel group study using different doses of
      dexmedetomidine added to ropiavcaine for ACB. Methods: A total of 150 patients
      aged 18-75 years, scheduled for simultaneous bilateral total knee replacement,
      received ultrasound-guided ACB. They were randomised into three groups -Group A
      received ACB with plain ropivacaine; Groups B and C received ACB with ropivacaine
      and addition of dexmedetomidine 0.25 MUg/kg and 0.50 MUg/kg, respectively, on
      each side of ACB. The primary outcome was the duration of analgesia. Total opioid
      consumption, success of early ambulation, and level of patient satisfaction were
      also assessed. Results: The patient characteristics and block success rates were
      comparable in all groups. Group C patients had longer duration of analgesia
      (Group C 18.4 h +/- 7.4; Group B 14.6 +/- 7.1; Group A 10.8 +/- 7; P < 0.001);
      lesser tramadol consumption (Group C 43.8 mg +/- 53.2; Group B 76.4 +/- 49.6;
      Group A 93.9 mg +/- 58.3; P < 0.001) and lesser pain on movement (P < 0.001). The
      patients in Group B and C walked more steps than in Group A (P < 0.002). The
      level of patient satisfaction was highest in Group C (P < 0.001). Conclusions:
      The addition of dexmedetomidine to ropivacaine resulted in longer duration of
      analgesia after adductor canal block for simultaneous bilateral total knee
      replacement surgery.

PMID- 29217857
TI  - A comparison of haemodynamic responses between clinical assessment-guided
      tracheal intubation and neuromuscular block monitoring-guided tracheal
      intubation: A prospective, randomised study.
AB  - Background and Aims: Haemodynamic responses to laryngoscopy and endotracheal
      intubation and their hazards are well documented. The purpose of the study was to
      compare the effects of laryngoscopy and intubation on cardiovascular responses
      when the appropriate moment for intubation was directed by either clinical
      judgment or train-of-four assessment. Methods: A total of 68 patients, posted for
      laparoscopic cholecystectomy, were randomised into two groups. In Group M
      patients, the trachea was intubated after train of four counts became zero in
      adductor pollicis muscle, whereas in Group C patients, the trachea was intubated
      after the clinical judgment of jaw muscle relaxation. Changes in heart rate (HR)
      and mean arterial pressure, intubating conditions and the time between the
      administration of a neuromuscular blocking agent and endotracheal intubation were
      recorded. Results were analysed by the Analysis of variance and chi-square tests.
      Results: HR and mean arterial pressure were significantly higher in Group C as
      compared to Group M after laryngoscopy and tracheal intubation (P < 0.05). The
      mean time required for intubation was significantly shorter in Group C compared
      to Group M (175 +/- 7 s vs. 385 +/- 101 s). Excellent and good intubation
      conditions were observed in all Group M patients, whereas 24 out of 34 patients
      (70%) in Group C showed excellent and good intubation conditions. Conclusion:
      Haemodynamic responses to laryngoscopy and tracheal intubation can be
      significantly attenuated if tracheal intubation is performed following complete
      paralysis of laryngeal muscles, detected by neuromuscular monitoring of adductor
      pollicis muscle.

PMID- 29217858
TI  - Effect of co-administration of different doses of phenylephrine with oxytocin on
      the prevention of oxytocin-induced hypotension in caesarean section under spinal
      anaesthesia: A randomised comparative study.
AB  - Introduction: Co-administration of phenylephrine prevents oxytocin-induced
      hypotension during caesarean section under spinal anaesthesia (SA), but higher
      doses cause reflex bradycardia. This study compares the effects of co
      administration of two different doses of phenylephrine on oxytocin-induced
      hypotension during caesarean section under SA. Methods: In this prospective,
      double-blind study, 90 parturients belonging to the American Society of
      Anesthesiologists' physical status 1 or 2, undergoing caesarean section under SA
      were randomised into Group A: oxytocin 3U and phenylephrine 50 MUg, Group B:
      oxytocin 3U and phenylephrine 75 MUg, Group C: oxytocin 3U and normal saline,
      administered intravenously over 5 min after baby extraction. The incidence of
      hypotension (the primary outcome), rescue vasopressor requirement and side
      effects were recorded. Statistical analyses were with analysis of variance,
      Kruskal-Wallis, chi-square and Fisher's exact tests. Results: Demographic
      parameters such as age, height, weight, level of sensory block at 20 min and
      duration of surgery were comparable in all the groups. The incidence of
      hypotension (Group A - 90%, Group B - 10%, Group C - 98%, P = 0.001), magnitude
      of fall in mean arterial pressure (Group A-15.03 +/- 6.12 mm of Hg, Group B -
      6.63 +/- 4.49 mm of Hg and Group C-13.03 +/- 3.39 mm of Hg, P < 0.001) and rescue
      vasopressor requirement (Group A-45 +/- 15.25 mg, Group B-5 +/- 15.25, Group C
      91.66 +/- 26.53, P < 0.001) were significantly lower in Group B compared to A and
      C. Conclusion: Co-administration of phenylephrine 75 MUg with oxytocin 3U reduces
      the incidence of oxytocin-induced hypotension compared to phenylephrine 50 MUg
      with oxytocin 3U during caesarean section under spinal anaesthesia.

PMID- 29217859
TI  - Efficacy of transdermal buprenorphine patch on post-operative pain relief after
      elective spinal instrumentation surgery.
AB  - Background and Aims: Transdermal buprenorphine patch (TDB) is increasingly used
      for chronic pain management because of non-invasive dosing, longer duration of
      action and minimal side effects. However its role in acute post-operative pain
      management for spinal instrumentation surgery is not well established. The aim of
      this study was to evaluate the analgesic efficacy of buprenorphine patch for
      postoperative pain relief in patients undergoing spinal instrumentation surgery.
      Methods: In this randomised, placebo-controlled, double-blinded, prospective
      study, 70 adult patients undergoing elective spinal instrumentation surgery were
      randomly allocated into two groups-TDB Group (buprenorphinepatch) and TDP Group
      (placebo patch). Time to first rescue analgesic requirement was the primary
      outcome. All patients also were monitored for total rescue analgesic requirement,
      drug-related adverse effect and haemodynamic status till 48 h after surgery.
      Statistical analysis was carried out using student independent t-test if normally
      distributed or with Mann-Whitney U-test if otherwise. Results: Time to first post
      operative rescue analgesic (tramadol) requirement was much delayed in TDB Group
      than TDP Group (708.0 +/- 6.98 min vs 54 +/- 0.68 min, P < 0.001) and the total
      tramadol requirement was higher in TDB Group (490.60 +/- 63.09 averagevs. 162.93
      +/- 63.91 mg, P < 0.001). Intra-and post-operative haemodynamic status was also
      stable in TDB Group without any adverse event. Conclusion: A TDB patch (10
      MUg/hour) applied 24 hours before surgery can be used as a postoperative
      analgesic for lumber fixation surgery without any drug-related adverse effect.

PMID- 29217860
TI  - Greater palatine nerve neuropraxia after laryngeal mask insertion: A rare
      occurrence.
AB  - With the more frequent use of the laryngeal mask airway (LMA) over endotracheal
      tubes for general anaesthesia, various cranial nerve injuries have been reported
      recently. We report a rare occurrence of greater palatine nerve (GPN) palsy
      subsequent to the use of LMA SupremeTM in a young female scheduled for hand
      surgery. Although the exact mechanism of a nerve injury is still a matter of
      further research, we postulate pressure neuropraxia of GPN as a causative factor
      in the development of numbness over the hard palate after the removal of LMA in
      the post operative period.

PMID- 29217861
TI  - Practice and reasons for routine pre-operative investigations among
      anaesthesiologists and surgeons: An online survey.

PMID- 29217862
TI  - Tracheostomal myiasis! A word of caution.

PMID- 29217863
TI  - Sustained intraoperative bradycardia revealing Sengers syndrome.

PMID- 29217864
TI  - Post-reperfusion bronchospasm in a deceased donor liver transplant recipient: An
      enigma.

PMID- 29217865
TI  - Jet Insufflator for cannot intubate cannot ventilate situation. An Indian Jugaad.

PMID- 29217866
TI  - Airway management of a paediatric patient with temporomandibular joint ankylosis
      with extra hepatic portal vein obstruction, splenomegaly, hypersplenism, and
      obstructive sleep apnoea for shunt surgery: A unique challenge.

PMID- 29217867
TI  - Ruthenium (II) and Iridium (III) Complexes of N-Heterocyclic Carbene and
      Pyridinol Derived Bidentate Chelates: Synthesis, Characterization, and
      Reactivity.
AB  - We report the synthesis and characterization of new ruthenium(II) and
      iridium(III) complexes of a new bidentate chelate, NHCR'-pyOR (OR = OMe, OtBu, OH
      and R' = Me, Et). Synthesis and characterization studies were done on the
      following compounds: four ligand precursors (1-4); two silver complexes of these
      NHCR'-pyOR ligands (5-7); six ruthenium complexes of the type [eta6-(p
      cymene)Ru(NHCR'-pyOR)Cl]X with R' = Me, Et and R = Me, tBu, H and X = OTf-, PF6-
      and PO2F2- (8-13); and two iridium complexes, [Cp*Ir(NHCMe-pyOtBu)Cl]PF6 (14) and
      [Cp*Ir(NHCMe-pyOH)Cl]PO2F2 (15). The complexes are air stable and were isolated
      in moderate yield. However, for the PF6- salts, hydrolysis of the PF6- counter
      anion to PO2F2- during t-butyl ether deprotection was observed. Most of the
      complexes were characterized by 1H and 13C-NMR, MS, IR, and X-ray diffraction.
      The ruthenium complexes [eta6-(p-cymene)Ru(NHCMe-pyOR)Cl]OTf (R = Me (8) and tBu
      (9)) were tested for their ability to accelerate CO2 hydrogenation and formic
      acid dehydrogenation. However, our studies show that the complexes transform
      during the reaction and these complexes are best thought of as pre-catalysts.

PMID- 29217868
TI  - Age Cohort Variation in Drinking among People with Physical Impairments:
      Politically-oriented Coping in the Wake of the Great Recession.
AB  - People with physical impairments are at greater risk for economic hardship and
      more alcohol-related problems compared to the general population. We address age
      cohort differences in modes of coping with economic adversity and the extent to
      which modes of coping explain the relationships between age cohort membership and
      drinking outcomes among people with physical impairments. 176 respondents with
      physical impairments derived from a national sample completed a mail survey.
      Using SEM, we demonstrate that members of the Generation X age cohort manifest
      higher levels of alcohol consumption and problem-related drinking compared to
      baby boomers due to their lesser tendency to engage in politically-oriented
      coping to deal with economic adversity. Within the context of social movements
      contesting the disadvantaged social status of people with disabilities, the
      Generation X age cohort manifests both more limited political engagement and
      higher levels of alcohol consumption and problem-related drinking among people
      with physical impairments.

PMID- 29217869
TI  - Leaf and root C-to-N ratios are poor predictors of soil microbial biomass C and
      respiration across 32 tree species.
AB  - Soil microorganisms are the main primary decomposers of plant material and drive
      biogeochemical processes like carbon and nitrogen cycles. Hence, knowledge of
      their nutritional demands and limitations for activity and growth is of
      particular importance. However, potential effects of the stoichiometry of soil
      and plant species on soil microbial activity and carbon use efficiency are poorly
      understood. Soil properties and plant traits are assumed to drive microbial
      carbon and community structure. We investigated the associations between C and N
      concentrations of leaf, root, and soil as well as their ratios and soil microbial
      biomass C and activity (microbial basal respiration and specific respiratory
      quotient) across 32 young native angiosperm tree species at two locations in
      Central Germany. Correlations between C:N ratios of leaves, roots, and soil were
      positive but overall weak. Only regressions between root and leaf C:N ratios as
      well as between root and soil C:N ratios were significant at one site. Soil
      microbial properties differed significantly between the two sites and were
      significantly correlated with soil C:N ratio across sites. Soil C concentrations
      rather than N concentrations drove significant effects of soil C:N ratio on soil
      microbial properties. No significant correlations between soil microbial
      properties and leaf as well as root C:N ratios were found. We found weak
      correlations of C:N ratios between plant aboveground and belowground tissues.
      Furthermore, microorganisms were not affected by the stoichiometry of plant
      tissues in the investigated young trees. The results suggest that soil
      stoichiometry represents a consistent determinant of soil microbial biomass and
      respiration. Our study indicates that stoichiometric relationships among tree
      organs can be weak and poor predictors of soil microbial properties in young tree
      stands. Further research in controlled experimental settings with a wide range of
      tree species is needed to study the role of plant chemical traits like the
      composition and stoichiometry of root exudates in determining interactions
      between above- and belowground compartments.

PMID- 29217870
TI  - Temporal Prediction of Future State Occupation in a Multistate Model from High
      Dimensional Baseline Covariates via Pseudo-Value Regression.
AB  - In many complex diseases such as cancer, a patient undergoes various disease
      stages before reaching a terminal state (say disease free or death). This fits a
      multistate model framework where a prognosis may be equivalent to predicting the
      state occupation at a future time t. With the advent of high throughput genomic
      and proteomic assays, a clinician may intent to use such high dimensional
      covariates in making better prediction of state occupation. In this article, we
      offer a practical solution to this problem by combining a useful technique,
      called pseudo value regression, with a latent factor or a penalized regression
      method such as the partial least squares (PLS) or the least absolute shrinkage
      and selection operator (LASSO), or their variants. We explore the predictive
      performances of these combinations in various high dimensional settings via
      extensive simulation studies. Overall, this strategy works fairly well provided
      the models are tuned properly. Overall, the PLS turns out to be slightly better
      than LASSO in most settings investigated by us, for the purpose of temporal
      prediction of future state occupation. We illustrate the utility of these pseudo
      value based high dimensional regression methods using a lung cancer data set
      where we use the patients' baseline gene expression values.

PMID- 29217871
TI  - Development and validation of European guidelines for seismic qualification of
      post-installed anchors.
AB  - This paper presents the technical background for the seismic qualification
      procedures for post-installed anchors in the European Technical Approval
      Guideline (ETAG 001) seismic annex issued in 2013. We discuss requirements for a
      comprehensive guideline and reference supporting documentation. Numerical studies
      to generate new simulated seismic protocols for anchors are summarized with focus
      on their application to Europe. To reduce the time and cost of anchor product
      qualification testing while fulfilling the requirement of European building codes
      to assess two performance categories, we combine the results of our numerical
      studies to generate novel testing protocols that allow for the assessment of
      anchor behavior at multiple levels in a unified protocol. Validation tests
      demonstrate that the unified protocol results in anchor performance comparable
      with that achieved in multiple, single-performance-level tests.

PMID- 29217873
TI  - Etale neighbourhoods and the normal crossings locus.
AB  - Given a property of the complete local ring of a variety at a point, how can we
      show that the set of all points on the variety sharing the same property is open
      or closed in the Zariski topology? Such questions are ubiquitous especially in
      resolution of singularities. In the example of the normal crossings property and
      some variations we give a solution via etale neighbourhoods and Artin
      approximation.

PMID- 29217872
TI  - An Integrated Bioprocess to Recover Bovine Milk Oligosaccharides from Colostrum
      Whey Permeate.
AB  - A major challenge in isolating oligosaccharides from dairy streams is to enrich
      oligosaccharides while simultaneously reducing the content of simple sugars (mono
      and disaccharides) that do not possess the desired prebiotic functions. An
      integrated approach based on optimized conditions that favor maximum lactose
      hydrolysis, monosaccharide fermentation and oligosaccharides recovery by
      nanofiltration was developed. Upon complete lactose hydrolysis and fermentation
      of the monosaccharides by yeast, nanofiltration of fermented whey permeate from
      colostrum enabled the recovery of 95% of the oligosaccharides at high purity.
      While the number of commercially available standards has limited the
      quantification of only a few sialylated oligosaccharides, the application of both
      high performance anion-exchange chromatography with pulsed amperometric detection
      and mass spectrometry provided a complete profile of the final product.
      Approximately 85% of the oligosaccharides in the final concentrate were
      sialylated, with the remainder being neutral.

PMID- 29217874
TI  - Measuring idiosyncratic interests in children with autism.
AB  - A defining symptom of autism spectrum disorder (ASD) is the presence of
      restricted and repetitive activities and interests, which can surface in language
      as a perseverative focus on idiosyncratic topics. In this paper, we use semantic
      similarity measures to identify such idiosyncratic topics in narratives produced
      by children with and without ASD. We find that neurotypical children tend to use
      the same words and semantic concepts when retelling the same narrative, while
      children with ASD, even when producing accurate retellings, use different words
      and concepts relative not only to neurotypical children but also to other
      children with ASD. Our results indicate that children with ASD not only stray
      from the target topic but do so in idiosyncratic ways according to their own
      restricted interests.

PMID- 29217875
TI  - Deep Auto-context Convolutional Neural Networks for Standard-Dose PET Image
      Estimation from Low-Dose PET/MRI.
AB  - Positron emission tomography (PET) is an essential technique in many clinical
      applications such as tumor detection and brain disorder diagnosis. In order to
      obtain high-quality PET images, a standard-dose radioactive tracer is needed,
      which inevitably causes the risk of radiation exposure damage. For reducing the
      patient's exposure to radiation and maintaining the high quality of PET images,
      in this paper, we propose a deep learning architecture to estimate the high
      quality standard-dose PET (SPET) image from the combination of the low-quality
      low-dose PET (LPET) image and the accompanying T1-weighted acquisition from
      magnetic resonance imaging (MRI). Specifically, we adapt the convolutional neural
      network (CNN) to account for the two channel inputs of LPET and T1, and directly
      learn the end-to-end mapping between the inputs and the SPET output. Then, we
      integrate multiple CNN modules following the auto-context strategy, such that the
      tentatively estimated SPET of an early CNN can be iteratively refined by
      subsequent CNNs. Validations on real human brain PET/MRI data show that our
      proposed method can provide competitive estimation quality of the PET images,
      compared to the state-of-the-art methods. Meanwhile, our method is highly
      efficient to test on a new subject, e.g., spending ~2 seconds for estimating an
      entire SPET image in contrast to ~16 minutes by the state-of-the-art method. The
      results above demonstrate the potential of our method in real clinical
      applications.

PMID- 29217877
TI  - Central Venous Stenosis: What Should a Nephrologist Know?

PMID- 29217876
TI  - Nocturnal Enuresis in India: Are We Diagnosing and Managing Correctly?
AB  - Nocturnal enuresis is a common problem affecting school-aged children worldwide.
      Although it has significant impact on child's psychology, it is always under
      recognized in India and considered as a condition which will outgrow with
      advancing age. Nocturnal enuresis classified as primary or secondary and
      monosymptomatic or nonmonosymptomatic. Factors that cause enuresis include
      genetic factors, bladder dysfunction, psychological factors, and inappropriate
      antidiuretic hormone secretion, leading to nocturnal polyuria. Diagnosis consists
      of detailed medical history, clinical examination, frequency-volume charts, and
      appropriate investigations. The frequency-volume chart or voiding diary helps in
      establishing diagnosis and tailoring therapy. The first step in treating
      nocturnal enuresis is to counsel the parents and the affected child about the
      condition and reassure them that it can be cured. One of the effective strategies
      to manage enuresis is alarm therapy, but currently, it is not easily available in
      India. Desmopressin has been used in the treatment of nocturnal enuresis for
      close to 50 years. It provides an effective and safe option for the management of
      nocturnal enuresis. This review covers the diagnosis and management of nocturnal
      enuresis and introduces the concept of "bedwetting clinics" in India, which
      should help clinicians in the thorough investigation of bedwetting cases.

PMID- 29217878
TI  - A Randomized Controlled Trial of Intravenous versus Oral Cyclophosphamide in
      Steroid-resistant Nephrotic Syndrome in Children.
AB  - This is a randomized, parallel group, active-controlled trial to compare the
      efficacy of intravenous cyclophosphamide (IVCP) with oral cyclophosphamide (OCP)
      in patients with steroid-resistant nephrotic syndrome (SRNS) in children. Fifty
      consecutive children with idiopathic SRNS were biopsied and then randomized to
      receive either OCP at a dose of 2 mg/kg/day for 12 weeks or IVCP at a dose of 500
      mg/m2/month for 6 months. Both groups received tapering doses of oral steroids.
      The response was evaluated in terms of induction of complete remission (CR) or
      partial remission (PR), time to remit, and side effects. The groups were followed
      up to determine the duration of remission, percentage of patients who remain in
      sustained remission for more than 1 year after completion of therapy, change in
      steroid response status, progression to chronic kidney disease stage 3 or more.
      Of the fifty patients, OCP was given to 25 children and IVCP to 25 children. The
      demographic data, histopathology, biochemical profile, and duration of follow-up
      in the two groups were comparable. The rates of induction of CR were 52% versus
      44% and of PR were 8% versus 8% in the intravenous (IV) and oral group,
      respectively. Time to remit was shorter with OCP than IVCP (53 days vs. 84.4
      days). Incidence of side effects (both major and minor) was 36% in IVCP versus
      20% in OCP group. The actuarial cumulative sustained remission in our study was
      12% in IVCP compared with 16% in OCP at 1 year after completion of therapy.
      Twelve percent children in both the groups exhibited restoration of steroid
      sensitivity. Thus, in our study, overall, more than half of SRNS patients showed
      initial response to cyclophosphamide, but only one-fourth patients had sustained
      remission on follow-up. OCP and IVCP were equally efficacious and safe in
      idiopathic SRNS in children.

PMID- 29217879
TI  - IgA-dominant Infection-related Glomerulonephritis in India: A Single-center
      Experience.
AB  - IgA-dominant infection-related glomerulonephritis (IRGN) is a distinct
      morphologic variant of IRGN, characterized by dominant or codominant glomerular
      deposits of IgA, mostly in elderly and patients with diabetes. More cases are
      being reported in recent times due to increased awareness of the disease entity
      and increased rate of Staphylococcus infection. It usually presents as rapidly
      progressive renal failure with proteinuria, and treatment guidelines for this
      disease entity are not well defined. We report here 12 cases of IgA-dominant IRGN
      seen over a period of 5 years from a single center. Clinical features, biopsy
      findings, treatment, and outcomes were analyzed. Out of 12 patients, eight were
      males. The mean age of presentation was 52.4 +/- 21 years. Skin was the most
      common site of infection seen in six patients. Gross hematuria was seen in 4
      patients and 11 had nephrotic proteinuria. Eleven had low serum C3. Only two
      patients had diabetes. Methicillin-resistant Staphylococcus aureus (MRSA) was the
      most common organism isolated in six patients. Most common histopathology was
      crescentic glomerulonephritis seen in seven patients, followed by endocapillary
      proliferation in three and diffuse proliferative glomerulonephritis in two.
      Hemodialysis was done in eight patients and six patients received steroid
      therapy. End-stage renal disease developed in three patients, chronic kidney
      disease in three, and three patients died due to sepsis. Various infections
      including MRSA and Escherichia coli were associated with IgA-dominant IRGN both
      in patients with diabetes and nondiabetics. Suspicion and recognition of the
      disease is important as it has therapeutic and prognostic implications.

PMID- 29217880
TI  - Renal Manifestation in Scrub Typhus during a Major Outbreak in Central Nepal.
AB  - Renal involvement and acute kidney injury (AKI) are common clinical
      manifestations seen in scrub typhus, a vector-borne tropical disease. There are
      no data on renal manifestation in scrub typhus in Nepal. We conducted a
      prospective study to analyze the incidence, urinary abnormalities, course,
      severity, outcome, and the predictors of AKI in patients with scrub typhus during
      a major outbreak in Central Nepal. Total 1398 patients admitted with acute
      febrile illness were subjected for Scrub Typhus DetectTM Immunoglobulin M (IgM)
      enzyme-linked immunosorbent assay (ELISA) test, of which 502 (35.90%) patients
      tested positive and were included in the study. Mean age of the patients was
      30.37 +/- 18.81 years (range, 1-79 years) with 26.29% in the pediatric age group.
      Female-to-male ratio was 1.26:1. Mean duration of fever was 6.8 +/- 3.1 days.
      Mean IgM ELISA value for scrub typhus was 2.17 +/- 1.70 without difference in AKI
      and non-AKI groups (2.17 +/- 1.76 vs. 2.16 +/- 1.62; P = 0.94). Urinary
      abnormalities were seen in 42.3% of patients. Mean serum creatinine was 1.37 +/-
      0.69 mg/dl with significant difference in two groups (1.85 +/- 0.87 vs. 1.03 +/-
      0.17; P = 0.003). AKI was seen in 35.8% of patients with majority having Stage 1
      AKI (68.3%) followed by Stage 2 (34.1%) and Stage 3 (1.2%). Hemodialysis was
      required for 3.94% of patients. In 54% of patients, AKI occurred in fifth and
      sixth day of fever. ICU admission was required for 18.73% of patients and 8.57%
      required ventilator support. Mortality rate was 1.79%, which was higher among
      patients with AKI (2.96% vs. 1.0%; P = 0.106). Multivariate analysis revealed
      that the presence of pneumonia, shock, and acute respiratory distress syndrome
      predicted the development of AKI.

PMID- 29217881
TI  - Reduced Baroreflex Sensitivity, Decreased Heart Rate Variability with Increased
      Arterial Stiffness in Predialysis.
AB  - High cardiovascular morbidity and mortality is observed in predialytic chronic
      kidney disease (CKD) patients. The underlying mechanism of cardiovascular
      dysfunction often remains unclear. The present study was designed to perform
      multiparametric assessment of baroreflex sensitivity (BRS), arterial stiffness
      indices, and cardiovascular variabilities (heart rate variability [HRV] and blood
      pressure variability [BPV]) together in predialytic CKD patients; compare it with
      normal healthy controls; and determine their relationships in predialytic
      nondiabetic CKD patients. Thirty CKD Stage 4 and 5 predialytic non-diabetic
      patients and 30 healthy controls were enrolled in the study. BRS was determined
      by spontaneous sequence method. Short-term HRV and BPV were assessed using 5 min
      beat-to-beat data of RR intervals and blood pressure by time domain and frequency
      domain analysis. Arterial stiffness indices - carotid-femoral pulse wave velocity
      (PWV) and augmentation index - were measured using SphygmoCor Vx device (AtCor
      Medical, Australia). Predialytic CKD patients had significantly low BRS, high
      PWV, and low HRV as compared to healthy controls. Independent predictors of
      reduced systolic BRS in predialytic CKD patient group on multiple regression
      analysis emerged to be increase in calcium-phosphate product, increase in BPV,
      and decrease in HRV. Predialytic nondiabetic CKD Stage 4 and 5 patients have poor
      hemodynamic profile (higher PWV, lower HRV, and reduced BRS) than healthy
      controls. Reduced HRV and altered calcium-phosphate homeostasis emerged to be
      significant independent predictors of reduced BRS.

PMID- 29217882
TI  - Innominate Vein Stenosis in Association with Ipsilateral Hyperdynamic
      Brachiobasilic Fistula Causing Ipsilateral Limb and Hemifacial Swelling.
AB  - A 34-year-old hypertensive woman with a hyperdynamic, left brachiobasilic
      dialysis fistula presented with a long history of throbbing in her head and
      swelling of the left side of the face. Tight stenosis of left brachiocephalic
      vein was found to be causing retrograde flow into the left jugular vein which
      normalized after dilatation and stenting with resolution of all the symptoms and
      patient is asymptomatic for 1 year.

PMID- 29217883
TI  - Squamous Cell Carcinoma of Skin after 20 Years of Renal Transplantation.
AB  - Solid organ transplant recipients are at high risk of developing malignancies due
      to the prolonged use of immunosuppressant drugs. Squamous cell carcinoma of skin
      can occur in these patients even after decades of organ transplant. A 45-year-old
      male underwent renal transplant for end-stage renal disease 23 years ago and was
      on immunosuppressive drugs since then. The patient was on regular follow-up.
      Three years back, he developed squamous cell carcinoma of both forearms and
      hands, which was treated with radiation therapy using 8 MeV electrons, by
      parallel opposed fields to a dose of 60 Gy/30 fractions. Complete response to
      treatment was achieved at 3 months posttreatment. The patient is currently on
      follow-up and asymptomatic for skin lesions. Hence, these patients require longer
      follow-up, active surveillance, and screening for early diagnosis and prompt
      treatment of the premalignant and malignant conditions.

PMID- 29217884
TI  - How Harmful Can Herbal Remedies Be? A Case of Severe Acute Tubulointerstitial
      Nephritis.
AB  - Acute interstitial nephritis (AIN) is a condition in which acute kidney injury
      (AKI) is characterized by the histological finding of interstitial inflammation.
      Hyponidd is an ayurvedic drug containing Momordica charantia, Gymnema sylvestre,
      Swertia chirata, etc., used for the treatment of Type 2 diabetes mellitus (DM)
      and polycystic ovarian disease as an insulin sensitizer. There are no case
      reports of AIN caused by this drug yet. We report a biopsy-proven case of AKI due
      to severe AIN associated with the use of hyponidd tablet in a 60-year-old male
      with DM and hypertension. As these types of various indigenous compounds are used
      as home remedies in our country, awareness about the possible adverse effects of
      these agents among physicians is very important in the early diagnosis and
      management.

PMID- 29217886
TI  - Methylene Blue Induced Methemoglobinemia with Acute Kidney Injury in a Glucose-6
      Phosphate Dehydrogenase-deficient Patient.
AB  - Our case was treated with methylene blue for symptomatic nitrobenzene poisoning.
      After which he developed methemoglobinemia with acute kidney injury due to
      hemolysis and on further testing, he was found to be glucose-6-phosphate
      dehydrogenase (G6PD) enzyme deficient. Thus, afterward, the patient was treated
      with only available mode of treatment as repeated blood transfusions and ascorbic
      acid with dialysis support to which the patient responded. Thus, it is important
      to evaluate for the G6PD deficiency where methylene blue treatment is planned as
      an antidote to nitrobenzene compounds poisoning.

PMID- 29217885
TI  - Acute Thyroid Swelling in Renal Transplant Recipient.
AB  - Tuberculosis (TB) of thyroid gland is rare entity even in solid organ transplant
      recipients who have a high risk of TB. Thyroid TB is easily diagnosed by fine
      needle aspiration cytology. The majority of cases require only antitubercular
      drugs for treatment, and surgical intervention is required only in few patients.
      We here describe a case of thyroid TB presenting as an acute abscess in postrenal
      transplant recipient with a background of acute rejection treated with steroid
      and antithymocyte globulin.

PMID- 29217887
TI  - Renal Complications of Hematopoietic Stem Cell Transplantation: Report of a Case
      and Review of the Literature.
AB  - We report the development of minimal change disease superimposed on preexisting
      chronic kidney disease secondary to chronic calcineurin inhibitor nephrotoxicity
      in a hematopoietic stem cell transplantation (HSCT) recipient and review the
      renal complications of HSCT.

PMID- 29217888
TI  - Nutcracker Syndrome with Hypertension as an Unusual Initial Presentation.
AB  - Hypertension has been rarely reported in patients with the nutcracker phenomenon
      (NCP)/syndrome. We describe a case of a young adolescent female patient where a
      computed tomography angiography (CTA) provided evidence of left renal vein
      dilatation, probably due to its compression through the angle between the aorta
      and the superior mesenteric artery, during the evaluation of secondary
      hypertension. Blood levels of renin and aldosterone were within normal limits.
      Ultrasonography of the kidney showed minimal scarring on the left side. As there
      were no other signs of secondary hypertension, we proceeded with a CTA, which
      revealed findings compatible with the so-called NCP/syndrome.

PMID- 29217889
TI  - Spontaneous Splenic Haematoma in a Patient on Hemodialysis: A Case Report.
AB  - Spontaneous splenic hematoma is one of the rare and life-threatening
      complications of chronic renal failure. The diagnosis of splenic hematoma is
      mostly made by imaging such as ultrasound or computed tomography. The management
      of spontaneous splenic hematoma is not standardized till now due to the rarity of
      this condition. Splenectomy is recommended in hemodynamically unstable patients
      with features of shock. This is a case report of spontaneous splenic hematoma in
      a patient with chronic renal failure. This case is reported due to the rarity
      with renal failure.

PMID- 29217890
TI  - Nontubercular Mycobacterial Infection in a Renal Allograft Recipient.
AB  - A 71-year-old male, a renal allograft recipient, presented to us with a history
      of fever and right palm swelling. He had a history of fever 7 years back when he
      was treated with antitubercular treatment (ATT). Three years back, he was
      diagnosed to have gout and he was started on allopurinol. He developed severe
      bone marrow toxicity and allopurinol was changed to febuxostat. On admission,
      routine investigations did not reveal any focus of infection. The fluid aspirate
      from the palm revealed acid-fast bacilli (AFB). He was started on ATT; however,
      he did not show significant improvement. Two months later, he developed multiple
      subcutaneous lesions, and the pus again came positive for AFB. Due to lack of
      improvement, the aspirate was sent for molecular diagnostic identification. The
      mycobacteria was identified as Mycobacterium haemophilum. His treatment was
      changed to rifampicin, clarithromycin, and ciprofloxacin. As he showed slow
      improvement, his immunosuppression was tapered slowly. At 7 months of therapy, he
      is clinically better and his lesions are healing. His renal functions stayed
      stable despite tapering of cyclosporine in a patient who is on rifampicin. This
      case, the first report of M. haemophilum infection in a kidney transplant
      recipient in India, illustrates the difficulty in diagnosing nontubercular
      mycobacterial infection in transplant recipients. It also emphasizes the dilemma
      in tapering immunosuppressive drugs in disseminated nontubercular mycobacterial
      infections where there are considerable interactions between ATT and
      immunosuppressives.

PMID- 29217891
TI  - Trimethoprim-Sulfamethoxazole-induced Hepatotoxicity in a Renal Transplant
      Patient.
AB  - Drug-induced liver injury (DILI) represents liver damage from various therapeutic
      drugs. Antimicrobials are among the most common causes of DILI. We report a case
      of hepatic toxicity due to Trimethoprim-sulfamethoxazole (TMP-SMX) in a patient
      who underwent renal transplantation. Diagnosis has been made after a careful
      history taking, exclusion of competing etiologies and reversal of biochemical
      abnormalities after withdrawal of the antibiotic. TMP-SMX liver toxicity is well
      known but remains unpredictable and is rarely reported.

PMID- 29217892
TI  - Bowel Migration of Dormant Chronic Ambulatory Peritoneal Dialysis Catheter: A
      Vexed Problem Not Avoided by Flushing.
AB  - Delayed bowel erosion by peritoneal dialysis catheter is rare with fewer than
      thirty cases having been reported in the literature. This complication is usually
      encountered when the catheter is kept dormant. Two cases have also been reported
      with catheters in active use. The risk factors for bowel erosion include
      immunosuppression, diverticulosis, and amyloidosis. An 80-year-old male with
      chronic kidney disease Stage 5 due to hypertensive nephrosclerosis underwent
      chronic ambulatory peritoneal dialysis catheter insertion. Due to improvement in
      the glomerular filtration rate and clinical parameters including extracellular
      fluid volume status, peritoneal dialysis was not initiated. Weekly catheter
      flushes were performed. After 5 months, he developed watery diarrhea after a
      regular flushing episode. Computed tomography scan revealed the catheter
      displaced into the sigmoid colon with the tip in the rectum. He was managed
      successfully with catheter removal alone and conservative treatment. He remains
      asymptomatic at 3-month follow-up. This case is presented to emphasize the fact
      that delayed bowel erosion can happen with dormant catheter even in the absence
      of risk factors. Periodic flushing has not prevented this complication in our
      patient. Perforations can be self-curing when diagnosed early and when patients
      present without features of peritonitis or sepsis. Such cases can be managed
      successfully with catheter removal alone.

PMID- 29217893
TI  - Strongyloid Hyperinfection Syndrome in a Renal Transplant Recipient.

PMID- 29217894
TI  - Streptococcus gallolyticus subsp. pasteurianus Peritonitis in a Patient on
      Continuous Ambulatory Peritoneal Dialysis.

PMID- 29217895
TI  - Efficacy of Thalidomide for Recurrent Gastrointestinal Bleeding due to
      angiodysplasias in a Hemodialysis Patient.

PMID- 29217896
TI  - Practice of Surgery-Decision, Precision, Incision.

PMID- 29217897
TI  - Long-Lasting Dysphagia Developing After Thoracotomy for Pulmonary Resection: a
      Case Series.
AB  - The purpose of this study was to retrospectively evaluate the severity and the
      characteristics of dysphagia using videofluoroscopic swallowing studies (VFSS) in
      long-lasting dysphagia patients developing after thoracotomy performed for
      pulmonary resection. Eleven patients (10 men and 1 woman, average age 67 +/- 6.6
      years; the average operation time in the patients was 507 min) were selected from
      among patients who developed dysphagia after undergoing thoracotomy for pulmonary
      resection between January 2009 and December 2012. The videofluoroscopic dysphagia
      scale (VDS) at 1 month postoperatively was used as a representative of parameters
      examined by the VFSS. The score on the functional oral intake scale (FOIS) was
      determined to evaluate the swallowing capacity at 1 and 3 months postoperatively.
      Most of the patients showed improvement of FOIS score at 3 months
      postoperatively. The patients showed mainly pharyngeal dysfunction. In spite of
      preserving the swallowing reflex, abnormalities of the residue in the vallecula
      and pyriform sinus and penetration were relatively frequent. Perioperative
      factors (age, %VC, FEV1.0 %, operation time, length of ICU stay) and FOIS were
      investigated to determine their relationships with the VDS score. While it showed
      no relationship with the age, lung function, operation time, and length of ICU
      stay, the VDS score was found to be significantly associated with the FOIS score
      at 3 months postoperatively. Evaluation by VFSS after lung surgery is useful to
      predict the prognosis of swallowing difficulty.

PMID- 29217898
TI  - Using of Ileucecal Interposition as a Neo-stomach in Dogs with Total Gastrectomy
      (Presentation of a Novel Technique).
AB  - Total gastrectomy and R&Y reconstruction is the standard treatment of gastric
      cancer except distal form one. Malnutrition is a common adverse effect of this
      technique, and in this study, we preset a novel technique in order to help to
      reduce the rate of it. We use seven dogs as participants and after total
      gastrectomy; we used the 10 cm of the ileum and its concomitant cecum as a neo
      stomach in them. For 3 months, the dogs were evaluated in nutrition status. Three
      of the dogs died-one due to endocarditis and two due to internal hernia. No
      anastomosis leakage or stricture was seen and there were no unusual neo-stomach
      dilation or food stasis. This technique can help the nutrition status of total
      gastrectomy patients but needs more comparative human studies.

PMID- 29217899
TI  - Technical Feasibility and Short-Term Outcome of Intracorporeal Hand-Sewn
      Esophagojejunostomy After Laparoscopic Total Gastrectomy: Our Experience.
AB  - The purpose of this study was to demonstrate the safety and technical feasibility
      of intracorporeal hand-sewn esophagojejunostomy after laparoscopic total
      gastrectomy. Laparoscopic total gastrectomy (LTG) is a technically challenging
      procedure, especially for esophagojejunal anastomosis (EJA). Various techniques
      have been described to overcome these difficulties using staplers with variable
      results. We report successfully performed complete intracorporeal hand-sewn EJA
      after LTG. The perioperative clinical data and short-term outcomes for 30
      patients who underwent LTG using hand-sewn EJA for gastric cancer between 2013
      and 2015 have been retrospectively reviewed. The mean age was 49.9 years; 64 % of
      patients were male and 36 % were female. The mean body mass index (kg/m2) was
      22.4, and the mean American Society of Anesthesiologists (ASA) score was 1.4.
      Eleven patients had co-morbidities, and six patients had previous abdominal
      operations. The mean operative time, time for EJA, and blood loss was 136.9 min,
      13.25 min, and 166 ml, respectively. The conversion rate was nil. The mean time
      for the first oral feeding and mean hospital stay was 8.3 and 9.8 days
      respectively. The postoperative complications were found in 16 % of patients with
      one case of 30-day mortality because of lobar pneumonia. There were three cases
      of anastomotic stenosis; however, no leakage was identified both clinically and
      radiologically. Complete intracorporeal hand-sewn EJA is a safe and feasible
      technique in the hands of experienced surgeons that can be considered as an
      alternative cost-effective method when performing LTG.

PMID- 29217900
TI  - Pulmonary Function After Lobectomy: Video-Assisted Thoracoscopic Surgery Versus
      Muscle-Sparing Mini-thoracotomy.
AB  - Although pulmonary function was better after video-assisted thoracoscopic surgery
      (VATS) lobectomy than after open thoracotomy lobectomy, it is unclear whether
      postoperative pulmonary function after VATS lobectomy is better than that after
      mini-thoracotomy lobectomy. The aim of this study is to determine whether the
      former is better than the latter. VATS lobectomies were performed using
      endoscopic techniques through a 3-4-cm skin incision spread by a silicon rubber
      retractor and two or three trocars. Mini-thoracotomy lobectomies were performed
      through a 7-12-cm skin incision spread by rib retractors made of metal and one or
      two trocars. Pulmonary function tests were performed a week before surgery and 3
      months after surgery. There were 14 males and 11 females in VATS lobectomy and 32
      males and 30 females in mini-thoracotomy lobectomy. For lobe location (right
      upper/right lower/left upper/left lower), there were 12/1/8/4 in VATS lobectomy
      and 16/19/13/14 in mini-thoracotomy lobectomy, respectively. The percent
      predicted postoperative forced vital capacity (FVC) (postoperative FVC/predicted
      postoperative FVC * 100) (110 +/- 15 %) of VATS lobectomy was significantly
      higher than that (101 +/- 16 %) of mini-thoracotomy lobectomy (P = 0.0124). The
      percent predicted postoperative forced expiratory volume in 1 s (FEV1)
      (postoperative FEV1/predicted postoperative FEV1 * 100) (110 +/- 15 %) of VATS
      lobectomy was not significantly higher than that (104 +/- 15 %) of mini
      thoracotomy lobectomy (P = 0.091). Multiple regression analysis revealed that
      operative procedure (VATS lobectomy or mini-thoracotomy lobectomy) was the only
      significant variable contributing to percent predicted postoperative FVC (P =
      0.0073) and percent predicted postoperative FEV1 (P = 0.0180). Postoperative FVC
      after VATS lobectomy is better than after mini-thoracotomy lobectomy.

PMID- 29217901
TI  - Xanthogranulomatous Cholecystitis: Analysis of 108 Patients.
AB  - The aim of this study was to evaluate the clinical and radiological features of
      xanthogranulomatous cholecystitis (XGC) and the results of surgical treatment.
      This retrospective study concerns clinical, radiological, and surgical data as
      well as histopathological findings and postoperative results of 108 patients with
      XGC who were identified after evaluating 7916 cholecystectomy specimens between
      2004 and 2014 in a single institute. One hundred eight patients with XGC were
      evaluated (56 males and 52 females, mean age 62.3 years). Clinical findings at
      referral included acute and chronic cholecystitis, Mirizzi's syndrome,
      choledocholithiasis, cholangitis, and acute pancreatitis. Ultrasound was
      performed in all patients, CT in 25, contrast-enhanced MRI in 29, and magnetic
      resonance cholangiopancreatography (MRCP) in 25 patients. None of the patients
      were diagnosed preoperatively, but mild-moderate degrees of wall thickening were
      present in most. Fifty-four patients received open cholecystectomy, while 54
      received laparoscopic intervention, among whom 23 were converted to open. Partial
      cholecystectomy was performed in 11 patients. Two patients with gallbladder
      adenocarcinoma were treated with radical cholecystectomy. XGC has nonspecific
      clinical and radiological findings; thus, preoperative diagnosis is generally
      absent. Open cholecystectomy is the recommended treatment modality. Conversion to
      open is frequently necessary after laparoscopy. Complete cholecystectomy is the
      ultimate goal; however, partial cholecystectomy may be preferred to protect the
      structures of the hepatic hilum.

PMID- 29217902
TI  - Magnitude, Severity, and Outcome of Traumatic Pancreatic Injury at a Level I
      Trauma Center in India.
AB  - Pancreatic injury is an uncommon and frequently missed injury in abdominal trauma
      patients. However, missed pancreatic injury is associated with significant
      morbidity and mortality. This study was conducted to know the burden of
      pancreatic injury and its outcome in our setup. A retrospective analysis of 53
      patients with pancreatic injury from January 2008 through March 2012 at the Jai
      Prakash Narayan Apex Trauma Center (JPNATC), All India Institute of Medical
      Sciences (AIIMS), New Delhi. Pancreatic injuries were present in 1.18 % of all
      trauma admissions. Blunt trauma to the abdomen (n = 49, 92.45 %) due to road
      traffic injury (n = 38, 71.70 %) was the most common mechanism of injury.
      Isolated pancreatic injury was present in eight (15.09 %) patients. Grade III
      pancreatic injury (n = 25, 47 %) was the most common. Of these patients, 18.86 %
      were managed nonoperatively and 81.13 % were managed operatively. Among the
      operatively managed patients (n = 43), 74.4 % were operated due to pancreatic
      injury and 25.5 % were operated due to associated injuries. Distal pancreatectomy
      with or without spleen preservation (n = 25) was the most common operative
      procedure done. Three out of five patients of Whipple operation for pancreatic
      injury died. Pancreatic injury was associated with complications in 43.40 % and
      death in 20 % (n = 11). Pancreatic injury is rare, but delay in diagnosis of
      pancreatic injury has been associated with higher morbidity and mortality. Low
      grade pancreatic injury with intact main pancreatic duct (MPD) could be
      successfully managed nonoperatively, whereas in high-grade pancreatic injury, an
      operative intervention is invariably necessary. Distal pancreatectomy with spleen
      preservation is a desirable goal whenever possible for distal transaction of the
      pancreas. Whipple resection should be reserved only for hemodynamically stable
      patients with complex pancreaticoduodenal injury and is associated with high
      mortality.

PMID- 29217903
TI  - Regression of Ophthalmopathic Exophthalmos in Graves' Disease After Total
      Thyroidectomy: a Prospective Study of a Surgical Series.
AB  - Autoimmune ophthalmopathy is one of the salient clinical features associated with
      Graves' disease. Exophthalmos is one of the commonest manifestations of Graves'
      associated ophthalmopathy. It is reported to regress after thyroidectomy
      favourably compared to radioiodine or antithyroid drug therapy. In this context,
      we present our experience based on a surgical series of Graves' disease. This is
      a prospective study of 15 patients of Graves' disease associated with
      ophthalmopathic exophthalmos. Preoperative and monthly postoperative evaluation
      of exophthalmos was done with Hertel's exophthalmometer, apart from documenting
      lid, extra-ocular muscle and orbital involvement. The minimum follow-up of the
      cohort was 12 months. The female to male ratio was 12:3 and the mean age of the
      subjects was 33.4 years (18-55). Exophthalmos was bilateral in 13 and unilateral
      in 2 patients. All the 15 patients underwent total thyroidectomy without any
      major morbidity. Exophthalmos regressed in 12 patients at a mean follow-up of
      15.6 +/- 6.4 months (14-38) and was static in 3. None of the cases had worsened
      ophthalmopathy at the final follow-up. Mean regression of exophthalmos was 2.1 mm
      (1-5). The regression was statistically significant at P value = 0.035. Surgery
      has a positive impact on the regression of ophthalmopathic exophthalmos
      associated with Graves' disease.

PMID- 29217904
TI  - Comparison of the Short-Term Outcomes of Laparoscopic and Open Resections for
      Colorectal Cancer in Patients with a History of Prior Median Laparotomy.
AB  - This study aimed to investigate the short-term outcomes of laparoscopic resection
      in comparison with those of open resection for colorectal cancer in patients with
      a history of prior median laparotomy (PML). Eighty-seven consecutive patients
      (87/1121, 7.8 %) with a history of PML who underwent major colorectal cancer
      resection were enrolled (laparoscopy, n = 40; open, n = 47). The conversion rate
      to open surgery was 25 % (n = 10). The laparoscopy group had a higher proportion
      of female patients (57.5 vs. 36.2 %), a lower rate of American Society of
      Anesthesiologists (ASA) score for physical status of >=3 (7.5 vs. 25.5 %), and a
      lower pT4 tumor rate (15 vs. 38.3 %) than the open resection group. Regarding the
      reasons for PML, radical hysterectomy with extended lymphadenectomy for
      gynecologic cancer was more common (32.5 vs. 4.3 %), but gastrointestinal
      surgeries, such as gastrectomy and colectomy, were less frequent in the
      laparoscopy group. Regarding intraoperative outcomes, the laparoscopy group
      showed a similar operative time (197 vs. 204 min), intraoperative enterotomy rate
      (2.5 vs. 2.1 %), and bowel resection rate (2.5 vs. 2.1 %) with the open resection
      group. Regarding postoperative outcomes, the laparoscopy group showed a lower
      complication rate (20 vs. 40.4 %), significantly reduced time to soft diet (5 vs.
      7 days), and shorter hospital stay (12 vs. 18 days). Despite the high rate of
      open conversion, favorable short-term outcomes were observed in the laparoscopic
      group. Laparoscopy may be chosen as the primary approach in selected patients
      with a history of non-gastrointestinal PML (prior abdominal surgery for
      gynecological cancer).

PMID- 29217905
TI  - OSCE as a Summative Assessment Tool for Undergraduate Students of Surgery-Our
      Experience.
AB  - Traditional examination has inherent deficiencies. Objective Structured Clinical
      Examination (OSCE) is considered as a method of assessment that may overcome many
      such deficits. OSCE is being increasingly used worldwide in various medical
      specialities for formative and summative assessment. Although it is being used in
      various disciplines in our country as well, its use in the stream of general
      surgery is scarce. We report our experience of assessment of undergraduate
      students appearing in their pre-professional examination in the subject of
      general surgery by conducting OSCE. In our experience, OSCE was considered a
      better assessment tool as compared to the traditional method of examination by
      both faculty and students and is acceptable to students and faculty alike.
      Conducting OSCE is feasible for assessment of students of general surgery.

PMID- 29217906
TI  - Liquid Paraffin vs Hyaluronic Acid in Preventing Intraperitoneal Adhesions.
AB  - Adhesion formation after abdominal and pelvic operations remains a challenging
      problem. Role of adjuvant barriers have been studied but there is no comparative
      study between liquid paraffin and hyaluronic acid as a barrier method. Hence, we
      planned to compare the effectiveness of 0.4 % hyaluronic acid and liquid paraffin
      in the prevention of postoperative intraperitoneal adhesions in rats. This
      prospective, randomized and controlled study was conducted in 60 adult Wistar
      albino rats. Surgical trauma by caecal abrasion and 1 g talcum powder was used in
      the rat model to induce adhesion formation. After trauma, 3 ml normal saline was
      instilled in the peritoneal cavity in control group (n = 20), 3 ml liquid
      paraffin was instilled in experimental group A (n = 20) and 3 ml 0.4 % hyaluronic
      acid was instilled in experimental group B (n = 20). Two weeks after laparotomy,
      repeat laparotomy was performed and the adhesions were scored according to Zuhlke
      classification. Liquid paraffin and hyaluronic acid both reduce the extent and
      grade of adhesions both macroscopically (p = 0.018, p = 0.017) and
      microscopically (p = 0.019, p = 0.019) respectively. Although there was
      significant reduction in adhesions by hyaluronic acid at certain specific sites
      as compared with liquid paraffin, its overall effectiveness in preventing
      postoperative intraperitoneal adhesions is not significantly different from
      liquid paraffin (p = 0.092, p = 0.193) respectively. The presence of liquid
      paraffin and hyaluronic acid in the peritoneal cavity reduce postoperative
      intraperitoneal adhesions significantly in rats. However, there is no overall
      significant difference in the effectiveness of two groups. Dosage and safety of
      these chemicals in human beings remains to be established.

PMID- 29217907
TI  - Synchronous Breast Cancer and Gallbladder Diseases-A Chromosomal Analysis: A
      Pilot Study at a Tertiary Care Centre.
AB  - Out of a total of 50 study-eligible patients, 15 patients were found to have
      synchronous breast cancer and gallbladder diseases. Fourteen such patients had
      breast cancer and cholelithiasis while 1 patient had breast cancer with
      gallbladder cancer. Amongst these 15 patients, 7 patients tested positive for
      chromosomal aberrations on karyotyping. Aberrations in these patients were seen
      on chromosomes 13 and 17 with 2 patients having deletion 13q, 2 having deletion
      17q, and 2 having deletions on 17p while one patient had multiple deletions on
      chromosomes 13q and 17p. The patient with multiple aberrations on 13q and 17p had
      a grade III infiltrating ductal carcinoma (NOS) of the breast with adenocarcinoma
      of the gallbladder. On the basis of our study and its analysis, we conclude that
      synchronous breast and gallbladder lesions are common amongst females and the
      occurrence of one should warn the clinician to search for the other. Also,
      chromosomal aberrations are common amongst patients with synchronous diseases and
      since these abnormalities are in the germ line cells, genetic counselling should
      be offered to the first- and second-degree female relatives.

PMID- 29217908
TI  - A Novel Method for Pain Relief in Chronic Pancreatitis: an Old Drug in a New
      Pack: a Controlled Study.
AB  - Most of pain-relieving agents in chronic pancreatitis are nonspecific and
      unpredictable. Omeprazole induces hypergastrinemia due to reduced gastric
      acidity. Raised serum gastrin, in turn, modulates to reduce secretin level.
      Secretin is responsible for secretion of almost 80 % bicarbonate-rich pancreatic
      juice from the ductular epithelium without affecting enzyme output. It is a
      prospective randomized study in patients with CT-confirmed chronic pancreatitis.
      The control group got the standard care and 60 mg of omeprazole twice daily was
      added to the test group. Absence of pain relief at 14 days was considered as
      failure. Pain relief, weight gain and any toxic effect of omeprazole were
      reviewed at 12 months. One hundred thirty-seven cases were included, with an age
      range of 19 to 72 years. (mean 42.67). The majority of them were alcoholic males.
      At 2 weeks, pain relief was noted in 47/69(68.1 %) and 63/65(96.96 %) in the
      control and omeprazole group, respectively. At the end of 1 year, the omeprazole
      group had greater weight gain (95 %) than the control group (69.5 %). All the
      pseudocysts in the omeprazole group and most in the control group resolved. No
      side effect of omeprazole was seen. The high-dose omeprazole (HDO) group of
      patients had significantly better pain relief in chronic pancreatitis than those
      treated with conventional therapy. A high number of cases gained weight in the
      HDO group than the controlled group. No patient had clinical, endoscopic,
      biochemical, or haematological toxicity of HDO. More studies are necessary.

PMID- 29217909
TI  - Predictive Factors for Small Intestinal and Colonic Anastomotic Leak: a
      Multivariate Analysis.
AB  - Anastomotic leak (AL) is a serious complication of intestinal surgery with
      various predisposing factors. This study aims to assess several risk factors
      associated with AL after small intestinal and colonic anastomoses through a
      multivariate analysis. Two hundred twenty-four patients (126 males) with
      intestinal anastomosis of a median age of 44 years were reviewed. Independent
      factors associated with AL were male gender (OR = 2.59, P = 0.02), chronic liver
      disease (CLD) (OR = 8.03, P < 0.0001), more than one associated comorbidity (OR =
      5.34, P = 0.017), anastomosis conducted as emergency (OR = 2.73, P = 0.012),
      colonic anastomosis (OR = 2.51, P = 0.017), preoperative leukocytosis (OR = 2.57,
      P = 0.015), and intraoperative blood transfusion (OR = 2.25, P = 0.037).
      Predicative factors significantly associated with AL were male gender, CLD,
      multiple comorbidities, emergent anastomoses, colonic anastomoses, preoperative
      leukocytosis, and intraoperative blood transfusion.

PMID- 29217910
TI  - Primary Tubercular Abscess of the Axilla-a Rare Case.
AB  - Tuberculosis can be broadly classified as pulmonary and extrapulmonary. Though
      pulmonary tuberculosis is the most common presentation, extrapulmonary
      tuberculosis is also an important entity. A tubercular cold abscess secondary to
      involvement of an adjacent bone or suppuration of lymph nodes is a well-known
      entity; however, a primary cold abscess is rare. We report a case of a young girl
      who presented with an axillary swelling which turned out to be a primary
      tubercular abscess of the axilla. To the best of our knowledge, this is the first
      reported case of a primary tubercular abscess presenting in the axilla. A primary
      tubercular abscess, though rare, should be considered as a possible diagnosis in
      appropriate clinical settings backed by evidence of Mycobacterium tuberculosis in
      form of AFB microscopy, L-J culture, BACTEC culture, or PCR test.

PMID- 29217911
TI  - Familial Occurrence of Thyroglossal Duct Cyst.
AB  - Thyroglossal duct cysts are one of the commonest benign midline neck swellings.
      These are the remnants of the embryologic duct that fails to regress by the 10th
      week of fetal development. Generally, these are sporadic, slowly enlarging
      midline neck lumps, with half of them presenting before the age of 30. However,
      despite their relative frequency, reports of familial inheritance are rare. A
      review of literature reveals a total of 25 patients from 8 families showing a
      familial inheritance pattern worldwide. We describe here a 9th family with 5
      affected patients taking the total number of cases to 30. Also, this is the 1st
      such reported case of familial inheritance of thyroglossal cyst from the Asian
      continent.

PMID- 29217912
TI  - Laparoscopic Transperitoneal Ureterouretrostomy for Retrocaval Ureter-a Case
      Report.
AB  - Retrocaval ureter is a rare developmental anomaly with an incidence of 1 in 1500
      births. The inferior vena cava compresses the ureter posteriorly, causing
      upstream dilatation of the proximal ureter and the kidney. We report a 16-year
      old girl who presented with right flank pain, diagnosed as retrocaval ureter with
      ultrasound, intravenous urogram and CECT, and was treated with laparoscopic
      transperitoneal ureteroureterostomy. Embryological aspects and laparoscopic
      technical considerations are highlighted in this case report.

PMID- 29217913
TI  - Aggressive Angiomyxoma of Inguinoscrotal Region Mimicking Inguinal Hernia: a Case
      Report.
AB  - Aggressive angiomyxoma (AAM) is a rare mesenchymal tumour of pelvis and perineum,
      almost exclusively occurring in females. We are reporting a case of a 53-year-old
      gentleman who presented with a long standing inguinoscrotal swelling misdiagnosed
      as inguinal hernia, for which he underwent incomplete excision at local hospital
      and then was referred to our centre for completion surgery.

PMID- 29217914
TI  - Skin Incision for Port Placement in Laparoscopic Surgery-an Often Forgotten
      Critical Step!
AB  - Port placement is the first and one of the most important step in laparoscopic
      surgeries. However, these incisions for port placement are often placed casually
      leading to larger or smaller incisions than those required. Larger incisions may
      lead to problems like oozing from skin incisions, egress of gas used to create
      pneuomoperitoneum, while smaller incisions lead to difficulty in port
      introduction and incision site skin necrosis. We describe a simple and novel
      technique of giving proper sized skin incision to avoid such problems.

PMID- 29217915
TI  - Innovative Economical Surgical Suture Board.
AB  - The aim of this study is to develop an economical suture board for practising
      suturing skills and techniques. Suture boards were made by using local electric
      boards, small leather patch, four suction buttons, six screws and a hook. These
      suture boards are multipurpose boards which are economical and available all the
      time in department for practicing. This board can also be placed in endotrainer
      for laparoscopic suturing skills. This economical suture board is cheap, easily
      available and helps in practicing various suturing and knot tying techniques.

PMID- 29217916
TI  - Hemorrhoid Treatment Needs a Relook: More Room for Conservative Management Even
      in Advanced Grades of Hemorrhoids.

PMID- 29217917
TI  - Surgical Checklists: Prevention Is Better Than Cure.

PMID- 29217918
TI  - Are Countries Fulfilling the Promise They Made to Prevent Non-Communicable
      Diseases (NCDs)?

PMID- 29217919
TI  - Attitude of Medical Students towards Psychiatry: The case of Jimma University,
      Southwest Ethiopia.
AB  - Background: The inability to attract medical graduates to specialize in
      psychiatry has always been a serious challenge to psychiatry training programs.
      Therefore, the aim of this study was to assess the attitude of medical students
      towards psychiatry. Methods: A comparative cross-sectional survey was conducted
      among 122 fourth year medical students of Jimma University. The attitude of
      medical students towards psychiatry was measured by Attitude toward Psychiatry -
      30 (ATP-30). The collected Data were analyzed by SPSS version-20 using
      independent samples t-test plus bivariate and multivariate logistic regression.
      The level of significance was determined at 95% confidence interval. Results:
      Medical students who did not take psychiatry clinical rotation had a higher ATP
      30 mean score 55.52(+/-15.2) indicating positive attitude towards psychiatry than
      those who completed psychiatry clinical rotation (mean= 49.75 +/-10.67). Female
      medical students had significantly more positive attitude towards psychiatry than
      males (OR=9.23, 95% CI: 2.32; 36.76). Medical students who did not take
      psychiatry clinical rotation had more positive attitude towards psychiatry than
      students who completed the psychiatry clinical rotation (OR=7.58, 95% CI: 2.02;
      28.37). Subjective experience of mental illness and reported family history of
      mental illness significantly predicted positive attitude toward psychiatry.
      Conclusion: The findings suggest that doing psychiatry rotation might have
      affected the attitude of medical students towards psychiatry. Future research
      should assess the experiential factors during psychiatry training of medical
      students that affect their attitudes. Also, future research needs to evaluate the
      attitudes of fourth year medical students before and after their psychiatry
      clinical rotation.

PMID- 29217920
TI  - Correlation between Serum Lipid Profile with Anthropometric and Clinical
      Variables in Patients with Type 2 Diabetes Mellitus.
AB  - Background: The problem of dyslipidemia is high in patients with diabetes
      mellitus. There is ample evidence that abnormalities in lipid metabolism are
      important risk factors for increased incidence of diabetes associated
      complications. The most important risk indicators for these complications are
      lipid profile abnormalities. Therefore, the aim of this study was to assess the
      correlation between serum lipid profile with anthropometric and clinical
      variables among type 2 diabetes mellitus patients. Methods: A comparative cross
      sectional study was conducted at University of Gondar Hospital from February to
      April in 2015. A total of 296 participants (148 case and 148 healthy controls)
      were selected using systematic random sampling technique. Socio-demographic
      characteristics and clinical data were collected using pretested structured
      questionnaire incorporating the WHO Stepwise approach. Fasting venous blood
      sample was collected for blood sugar; lipid profile investigations and the blood
      levels were determined by Bio Systems A25 Chemistry Analyzer (Costa Brava,
      Spain). Independent sample t-test and Man Whitney U test were used to compare
      means. P-value < 0.05 was considered statistically significant. Results: Overall,
      T2DM patients had significantly higher total cholesterol ([205.4+/-50.9vs184.9+/
      44.1]mg/dl), low density lipoprotein ([113.1+/-43.2vs100.1+/-36.4] mg/dl) and
      triacylglycerol ([189.22+/- 100.9 vs 115.13+/-59.2] mg/dl), and significant
      decline of high density lipoprotein cholesterol ([56.5+/-20.4vs62.1+/-13] mg/dl)
      as compared to healthy controls, respectively. Triacylglycerolemia was
      significantly associated with the risk of cardiovascular disease (AOR: 1.015;
      95%CI: 1.010-1.021). Evident correlation was observed between anthropometric and
      clinical variables with lipid profile. Conclusion: Higher serum levels of fasting
      blood sugar, total cholesterol, low density lipoprotein cholesterol, and
      triacylglycerol and lower levels of high density lipoprotein cholesterol are
      found in type 2 diabetes mellitus patients. Thus, DM patients are more prone to
      dyslipidemia which is an important risk factor for atherosclerosis and coronary
      heart disease.

PMID- 29217921
TI  - Dietary Patterns and Metabolic Syndrome among Type 2 Diabetes Patients in Gaza
      Strip, Palestine.
AB  - Background: The prevalence of metabolic syndrome is raising worldwide; however,
      the role of diet in the origin of metabolic syndrome is not understood well. This
      study identifies major dietary patterns among type 2 diabetes mellitus patients
      with and without metabolic syndrome; and its association with metabolic syndrome
      components in Gaza Strip, Palestine. Methods: This cross sectional study was
      conducted among 1200 previously diagnosed type 2 diabetes mellitus (both genders,
      aged 20 - 64 years) patients receiving care in primary healthcare centers in Gaza
      Strip, Palestine. Metabolic syndrome was defined based on the International
      Diabetes Federation criteria; dietary patterns were evaluated using a validated
      semi-quantitative food frequency questionnaire. Statistical analysis was
      performed using SPSS version 20. Results: Two major dietary patterns were
      identified by factor analysis: Asian-like pattern and sweet-soft drinks-snacks
      pattern. After adjustment for confounding variables, patients in the highest
      tertile of the Asian-like pattern characterized by a high intake of whole grains,
      potatoes, beans, legumes, vegetables, tomatoes and fruithad a lower odds for
      (Metabolic syndrome, central obesity, high triglycerides, low HDL cholesterol and
      high blood pressure), (OR 0.766 CI 95% (.642-.914)), (OR 0.797 CI 95% (.652
      .974)), (OR 0.791 CI 95% (.687-.911)), (OR 0.853 CI 95% (.743-.978)) and (OR
      0.815 CI 95% (.682-.973)) respectively, (P value < 0.05 for all). No significant
      association was found between the sweet-soft drinks-snacks pattern with metabolic
      syndrome and its components. Conclusion: The Asian-like pattern may be associated
      with a lower prevalence of metabolic syndrome and its components among type 2
      diabetes patients.

PMID- 29217922
TI  - Effect of Solanum Nigrun on Uterus of Non-gravid Rats.
AB  - Background: Solanum nigrum is a widely used plant in oriental medicine where it
      is considered to be antioxidant, anti- inflammatory and diuretic. This study
      aimed to evaluate the effect of Solanum Nigrum on uterine contractions. Method:
      Female Wistar Wister albino rats were used for the study. They were housed in a
      single large cage in an atmospheric controlled environment. Twenty-four hours
      before every experiment, 0.2 mg/kg of diethylstilbesterol constituted in 1:1
      ethanol/water solution, was administered intraperitoneally as a pre-treatment to
      the rats to induce oestrus. It was done for two weeks during the study period.
      The phytochemical analysis was carried out to test for the phytochemical
      constituent of the plant. Result: The result showed that the extract inhibited
      the release of intracellular calcium ion. The effect of acetylcholine was
      significantly inhibited by the extract that is at 200mg/ml (p>0.05) and 300 mg/ml
      (p<0.01). The highest mean inhibitory effect of the extract observed on
      acetylcholine induced contractions was 90.54 +/- 1.15. The oxytocin induced
      contraction was significantly inhibited by the extract at 200 mg/ml (p<0.05) and
      at 300 mg/ml (p<0.001) doses respectively. The highest mean inhibitory effect of
      the extract observed on Oxytocin induced contractions was 41.10+/-1.02 and was
      significantly stronger compared with acetylcholine induced contractions.
      Conclusion: The aqueous extract of Solanum nigrun inhibited the activity of
      oxytocin on the uterus, and it may possess relaxant activity.

PMID- 29217923
TI  - Enhancing Personal Hygiene Behavior and Competency of Elementary School
      Adolescents through Peer-Led Approach and School-Friendly: A Quasi-Experimental
      Study.
AB  - Background: Recent studies showed that poor personal hygiene practices play a
      major role in the increment of communicable disease burden in developing
      countries. In Ethiopia, 60% of the disease burden is related to poor sanitation
      practices. This school based study was aimed to assess the effectiveness of
      school-friendly and peer-led approach in improving personal hygiene practices of
      school adolescents in Jimma Zone, Southwest of Ethiopia. Methods: A total of 1000
      students from 10 to 19 years were included into the study. The intervention was
      done using peer-led approach, health clubs and linking the school events with
      parents. Data were collected at baseline, midline and end-line using structured
      questionnaires. Repeated measurement analysis was done and statistical
      significance was considered at alpha 0.05. Results: The findings of this study
      indicated that there was a significant difference in personal hygiene practices
      and knowledge between the intervention and control groups (P<0.001). A
      significant difference was also observed with the duration of time in the
      intervention schools (P<0.05). The proportion of adolescents who reported illness
      before the baseline survey was significantly high among the intervention schools
      (P<0.01). However, at midline of the survey, the proportion of self-reported
      illness was significantly high among the control group(P<0.001). Conclusion: The
      findings of this study showed that there was a significant improvement in
      personal hygiene knowledge and practice of students in the intervention schools.
      Therefore, there is a need for proper health education intervention through the
      framework of schools for the students to improve their personal hygiene knowledge
      and practices.

PMID- 29217924
TI  - Types of Cancers Diagnosed and the Preference of Families of Adult Patients with
      Cancer about Disclosing Diagnosis to the Patients.
AB  - Background: Cancer has become one of the top causes of death in developing
      nations killing more people than the common infectious diseases do. For several
      reasons, disclosing cancer diagnosis to the patient is a challenging job for
      physicians and family members. Materials and Methods: A cross-sectional study was
      done to determine the common cancer diagnosis and the preference about disclosing
      cancer diagnosis to the patients among attendants of adult cancer patients seen
      at the regular surgical OPD of St. Paul's Hospital Millennium Medical college
      (SPHMMC) in June 1-31st 2015. Medical records of the patients and face-to-face
      interview with attendants were used to generate the data and analysis was done
      with SPSS version 19.0. Results: A total 112(7.3%) patients were diagnosed to
      have cancer and 104 attendants (93%) were interviewed. The mean age of the
      patients was 48.2 years, Females made up 59% of the patients. The commonest
      cancer diagnosed was breast cancer. Male (62.7%) and children (36.1%) were the
      main attendants. Only 56.6% of the attendants agreed that patients should be the
      first to know diagnosis results. When possible, 84.3% preferred to hide
      diagnosis. Although 81.3% attendants did not like diagnosis disclosure to the
      patient, all of them wanted to know the diagnosis if they develop cancer. Nearly
      all, 98.8%, of the attendants preferred to hear the diagnosis from their doctors.
      Conclusions: Cancer is a relatively common diagnosis occurring at a younger age.
      The rate of cancer diagnosis disclosure acceptance and practice by attendants was
      low. Population-based and multicentre study with a larger sample size is
      recommended to define the condition better.

PMID- 29217925
TI  - Prevalence and Factors Associated with Pelvic Organ Prolapse among Pedestrian
      Back-Loading Women in Bench Maji Zone.
AB  - Background: It is common to see women carrying heavy loads on their back in
      developing countries including Ethiopia. This may have an effect on pelvic organ
      prolapse. The objective of this study was to determine prevalence and factors
      associated with pelvic organ prolapse among pedestrian back-loading women in
      Bench-MajiZone, 2016. Methods: The study was conducted in Bench-MajiZone,
      Southwest Ethiopia, from January to March 2016. Cross-sectional study design was
      employed. The sample size was calculated to be 422. Women were selected by using
      convenientsampling technique. Interviewer-administered questionnaire was used to
      collect data. Binary logistic regression was used to determine factors associated
      with pelvic organ prolapse. Results: Fifty-six (13.3%)of the study participants
      had pelvic organ prolapse. The likelihood of pelvic organ prolapse was higher
      among women whose ages were between 31-40 years (AOR= 6.88: 95% CI 1.68, 28.23),
      41-50 years (AOR= 11.10: 95% CI 2.54, 48.49) and above 50 years (AOR= 35.42: 95%
      CI 6.94, 180.85) as compared with those who were less than 30 years. The
      likelihood of pelvic organ prolapse was also higher among those whose BMI was
      less than 18.5 (AOR= 2.37: 95% CI 1.25, 4.51) and duration of work greater than
      10 years (AOR= 4.01: 95% CI 1.81, 8.89). Conclusion: The prevalence of pelvic
      organ prolapse was high. Age, BMI and duration of work were significantly
      associated with pelvic organ prolapse. Urgent attention is needed from concerned
      bodies.

PMID- 29217926
TI  - The Association between Physical Activity and the Metabolic Syndrome among Type 2
      Diabetes Patients in Gaza Strip, Palestine.
AB  - Background: Metabolic syndrome is a major health problem worldwide. Globally, the
      World Health Organization identified physical inactivity as the fourth leading
      risk factor for mortality. This study was conducted to evaluate the association
      between physical activities and metabolic syndrome and diabetes complications
      among type 2 diabetes patients in Gaza Strip, Palestine. Methods: This cross
      sectional study was conducted among 1200 previously diagnosed type 2 diabetes
      mellitus patients (from both genders, aged 20 to 64 years) receiving care in the
      primary health care centers. Metabolic syndrome was defined based on the
      International Diabetes Federation criteria. The International Physical Activity
      Questionnaire was used to measure physical activity. Statistical analysis was
      performed using SPSS version 20. Results: A significant inverse association was
      found between inactive patients and metabolic syndrome. In our study, 93.7% of
      inactive patients, 66.4% of active patients and 23.5% of very active patients had
      metabolic syndrome (OR .048 CI 95% (.03-.072)), (OR .787 CI 95% (.59-1.03)) and
      (OR 15.9 CI 95% (11.8-21.3)) respectively. Our results showed a significant
      inverse association between physical activity levels and anthropometric
      measurements in both gender. Moreover, a significant association was found
      between physical activity levels and triglycerides, HDL-cholesterol and blood
      pressure in both sexes (P value < 0.05 for all) and diabetes complications (P
      value < 0.05 for all). Conclusion: We conclude that low levels of physical
      activity are associated with increased prevalence of metabolic syndrome.
      Furthermore, inactive patients had a high percentage of diabetes complications
      among type 2 diabetes patients in Gaza Strip, Palestine.

PMID- 29217927
TI  - Magnitude and Factors Associated With Post-Cesarean Surgical Site Infection at
      Hawassa University Teaching and Referral Hospital, Southern Ethiopia: A Cross
      sectional Study.
AB  - Background: Surgical site infection (SSI) after cesarean section (CS) increases
      maternal morbidity, hospital stay and medical cost. However, in Ethiopia, limited
      evidence exists regarding the magnitude and risk factors of post-CS wound
      infection. The purpose of this study was to determine the prevalence of - and
      factors associated with the problem among mothers who gave birth in Hawassa
      University Teaching and Referral Hospital, Southern Ethiopia. Methods: Hospital
      based cross-sectional study was conducted based on the medical records of 592
      women who underwent CS from June 2012 to May 2013. Data on the occurrence and
      factors associated with SSIs were extracted. Factors associated with SSI were
      identified using multivariate logistic regression analysis. The output of the
      analysis is presented using adjusted odds ratio (OR) with the corresponding 95%
      confidence interval (CI). Results: The prevalence of SSI was 11.0% (95% CI: 8.6
      13.8%). Mothers with prolonged labor (6.78, 95% CI: 2.54-18.00) and prolonged
      rupture of membrane (5.83, 95% CI: 2.14-15.89) had significantly increased odds
      of SSI. Compared to mothers who had no digital vaginal examination, those who had
      1-4 and 5 or more examinations were at higher risk with OR of 2.91 (95% CI: 1.21
      6.99) and 8.59 (95% CI: 1.74-42.23), respectively. Prolonged duration of surgery
      (12.32, 95% CI: 5.46-27.77), wound contamination class III (9.61, 95% CI: 1.84
      50.06) and postoperative anemia (2.62, 95% CI: 1.21-5.69) were also significant
      predictors. CS conducted by junior practitioners is likely to be followed by
      infection. Conclusion: Post-CS SSI is relatively common in the hospital. Thus, it
      should be averted by implementing infection prevention techniques.

PMID- 29217928
TI  - Determinants of Skilled Care Utilization among Pregnant Women Residents in an
      Urban Community in Kwara State, Northcentral Nigeria.
AB  - Background: Skilled attendant at delivery (SBA) is one of the key indicators used
      in assessing progress towards improved maternal health. This study aimed at
      identifying factors influencing SBA utilization in Ilorin, Nigeria. Methods: This
      cross-sectional study was carried out using multi-stage sampling technique among
      400 participants in Ilorin, Northcentral Nigeria. A pre-tested questionnaire was
      used for data collection, and data analysis was done using descriptive and
      inferential statistics. Results: SBA supervised 73.8% births. Determinants of
      skilled birth attendance at delivery include higher education (AOR; 10.94, 95%
      CI; 3.60-33.26), having only one child (AOR; 4.33, 95% CI; 1.18-15.82), having at
      least 4 ANC attendance (AOR; 18.84, 95% CI; 8.95-55.82) and residing near
      delivery sites (AOR; 11.49, 95% CI; 2.43-55.56). Conclusion: The proportion of
      births supervised by SBA needs improvement in Northcentral Nigeria. Full
      implementation of reproductive health policies will enhance skilled births in
      Nigeria.

PMID- 29217929
TI  - Maternal vitamin D deficiency: A Culprit for Hypocalcaemia Induced Myocardial
      Failure in a Four-Month Old Infant: A Case Report From Tikur Anbessa Specialized
      Hospital, Ethiopia.
AB  - Background: A rare but reversible cause of dilated cardiomyopathy occurs in
      infants born to vitamin D deficient mothers due to hypocalcaemia. Case Report: We
      report a case of dilated cardiomyopathy due to hypocalcaemia secondary to
      maternal vitamin D deficiency in an infant presented with seizure disorder and
      heart failure. This was a four-month old female infant with respiratory distress
      and acute heart failure. The cause of her cardiac failure was dilated
      cardiomyopathy. Concomitant community acquired pneumonia was diagnosed on chest X
      ray. Despite treatment, the infant's clinical condition worsened. The mother was
      found to be house-bound, dark skinned and veiled while going outside of home.
      Laboratory studies revealed hypomagnesaemia and hypocalcaemia. The vitamin D
      levels of both the infant and the mother were found to be low. The infant was
      treated for the deficiency state until her cardiac condition fully recovered.
      Conclusion: This case report demonstrated the direct relationship between
      maternal vitamin D deficiency and the infant's acute heart failure. It also
      highlighted the importance of vitamin D supplementation during pregnancy in order
      to prevent the cardiac complication of maternal vitamin D deficiency in the
      infants.

PMID- 29217930
TI  - Symptomatic Cholilithiasis and Cholecystectomy for a 9-Month-Old Infant: A Case
      Report.
AB  - Background: Symptomatic cholilithiasis is rare in children. Thus, a high degree
      of suspicion is required for diagnosis. Once a child is diagnosed with
      symptomatic cholilithiasis, cholecystectomy is required to relieve the symptoms
      and prevent complication. Case Details: A 9-month-old infant from Addis Ababa
      presented to the Pediatric Department of ZewdituMemorial Hospital on January 30,
      2015 with irritability, abdominal pain. On workup, she was found to have gall
      stones, and her condition was at last attributed to biliary colic after months of
      follow-up in the Department of Pediatrics. She underwent cholecystectomy on the
      31st of July 2015 and discharged with improved results. This is the first report
      of symptomatic cholilithiasis and cholecystectomy in Ethiopia at 9 months of age.
      Conclusion: Cholilithiasis is rare in infants, and one should have a high index
      of suspicion for diagnosis. Cholecystectomy should be done as in adults if
      symptomatic.

PMID- 29217931
TI  - Hyper Parathyroidisim Jaw Tumor Syndrome: A Rare Condition of Incongruous
      Features.
AB  - Background: Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome is a rare genetic
      disorder bearing both a germline and a somatic CDC73 mutation (formerly known as
      HRPT2), which has been mapped to chromosome 1q25-q31. The association of jaw
      ossifying fibroma with primary hyperparathyroidisim (PHPT) is typical of HPT-JT.
      It may also include cystic and neoplastic renal abnormalities and uterine tumors.
      Case Details: Here, we report a case of HPT-JT with an initial presentation of
      declination in reproductive fitness. Extensive literature search and thorough
      investigation helped us parturitate the underlying syndrome, thereby predictively
      improving the prognosis. Conclusion: The features of HPT-JT are clinically
      difficult to ascertain because the parathyroid disease, ossifying fibroma in the
      jaw and other abnormalities, often occurs asynchronously and may be diagnosed and
      treated separately.

PMID- 29217932
TI  - Why is the Under-5 Mortality Rate in Ethiopia Slipped Back?

PMID- 29217933
TI  - Data Sharing Statements for Clinical Trials: A Requirement of the International
      Committee of Medical Journal Editors.

PMID- 29217934
TI  - The Prevalence of Antibiotic Resistant Diarrhogenic Bacterial Species in Surface
      Waters, South Eastern Nigeria.
AB  - Background: This study assessed the bacteriological qualities of surface waters
      in Afikpo, between April and September 2016. Methods: Surface water samples were
      collected from three streams for bacteriological analysis. Bacteria species were
      isolated using standard microbiological and biochemical techniques. Antibiotic
      susceptibility study was carried out using Kirby Bauer disc diffusion method.
      Results: The result of the mean heterotrophic bacteria count from the streams
      showed that Okpu stream had 209.5CFU/100 mL, Ohino Ngodo 162.5 CFU/100mL, and
      Ngwogo stream 162.0 CFU/100mL respectively. Out of the twenty-six (26) isolates
      obtained, E. coli and Staphylococcus species had the highest percentage
      occurrence (23.1%) respectively. Klebsiella, Shigella and Enterobacter sp had
      (11.5%) each, Pseudomonas spp (7.7%), while Salmonella and Streptococcus sp had
      the least percentage occurrence of (3.8%). The antibiotic susceptibility studies
      showed that large proportions of isolates were resistant to sulphamethaxoid
      (SUL), cephalothin (CEP), tetracycline (TET), penicillin G (PEN), oxytetracycline
      (OXY), cefotaxime (CEF), nalidixic acid (NAL) and cefuroxime sodium (CXM). The
      most effective antibiotic was azithromycin followed by imipenem. Conclusion: The
      presence of these multi-drug resistant strains in water samples could facilitate
      transmission of antibiotic resistance. This emphasizes the need for proper
      treatment of water in the study area.

PMID- 29217935
TI  - Bronchoscopy in Nigerian Clinical Practice: A Survey of Medical Doctors'
      Perception, Use and Associated Challenges.
AB  - Background: Bronchoscopy is a vital diagnostic and therapeutic procedure in
      pulmonological practice. The aim of this study was to determine the perception,
      use and challenges encountered by Nigerian medical doctors involved in this
      procedure. Materials and Methods: A cross-sectional study was conducted among 250
      medical doctors recruited from three major tertiary institutions in Nigeria
      between September 2013 and June 2014. A semi-structured questionnaire was self
      administered to adult physicians, paediatricians, and surgeons as well as their
      trainees to obtain their perception, use and associated challenges in the use of
      bronchoscopy in clinical practice. Results: The majority (91.6%) of the
      respondents perceived bronchoscopy as a beneficial procedure to respiratory
      medicine. However, 59.2% of them were not aware of the low mortality rate
      associated with this procedure. The commonest indications for bronchoscopic use
      were foreign body aspiration (88.8%) and management of lung tumors (75.6%). Only
      21 (8.4%) of the respondents had received formal training in bronchoscopy. Very
      few procedures (1-5 cases per month) were performed. The respondents identified
      the lack of formal training in the art of bronchoscopy as the foremost challenge
      facing its practice in Nigeria. In addition, availability of bronchoscopes, level
      of awareness, knowledge of the procedure among medical doctors and the cost of
      the procedure were the challenges faced by the medical doctors. Conclusion: There
      is an urgent need to equip training centers with modern bronchoscopic facilities.
      In addition,well-structured bronchoscopic training programme is imperative to
      enhance the trainees' proficiency for the furtherance of bronchoscopic practice.

PMID- 29217936
TI  - Utilization of Primary Health Care Services in Jaba Local Government Area of
      Kaduna State Nigeria.
AB  - Background: Primary health care was designed to provide accessible health care
      for all. However, most primary health care facilities are in various states of
      disrepair, catering for less than 20% of potential patients in the population.
      This study was designed to investigate the utilisation of primary health care
      services in Jaba Local Government Area of Kaduna State Nigeria. Methods: The
      study employed a cross-sectional study design conducted among 383 respondents
      utilising simple random sampling techniques. A pretested semi-structured
      questionnaire was administered to obtain information from respondents, while
      descriptive statistics was used to analyse the data. Results: The results show
      that almost all of the respondents, 333(97.90%), were aware of the existence of
      primary health care services in their community. Furthermore, the majority of the
      respondents, 304(89.40%), utilized primary health care services while 293(86.20%)
      and 212(62.40%) were satisfied with the amount of charges for services and the
      supply of drugs respectively. According to the respondent, weak services in
      primary health care includes; personal hygiene and nutritional education,
      management of chronic diseases and cancer screening. Factors that influence the
      utilization of primary health care services according to the respondents were
      availability of trained personnel (AOR=1.828 95% CI=0.410-1.672), attitude of
      staffs (AOR=1.114 95% CI=0.527-2.355), waiting times (AOR=1.110 95% CI=0.584
      2.224) and availability of diagnostic services (AOR=0.951 95% CI=0.472-1.918).
      Conclusion: The study highlighted the weaknesses in some of the services offered
      at the various primary health centres and the factors which can hinder the
      residents from patronizing primary health care services.

PMID- 29217937
TI  - Are Past Adverse Pregnancy Outcomes Associated with Maternal Anxiety and
      Depressive Symptoms in a Sample of Currently Pregnant Women?
AB  - Background: There has been a great deal of concern about the mental health of
      women whose pregnancies involve miscarriage, termination of a pregnancy (ToP),
      child death or where a child has been given up for adoption. Despite this concern
      there has been remarkably little population-based research which has addressed
      the long-term consequences of pregnancy loss and child death. This study
      investigated the maternal mental health consequences of women whose pregnancies
      involve miscarriage, ToP, child death or where a child has been given up for
      adoption at two different time points, adjusting for socio-demographic
      characteristics and baseline mental health. Methods: The Mater-University of
      Queensland Study of Pregnancy is a prospective pre-birth cohort study. Women were
      recruited early in pregnancy over the period 1981 to 1983 at their first
      antenatal clinic visit (FCV). Women were interviewed again at the 14-year follow
      up. Data from 4403 mothers were analysed using maternal reports of a prior
      history of giving a child up for adoption, miscarriage, ToP, and neonatal, infant
      and/or child deaths. Symptoms of maternal anxiety and depression were measured at
      FCV and the 14-year follow-up using the Delusions-Symptoms-States Inventory. We
      carried out logistic regression analysis using Stata 13. Odds ratios (ORs) with
      95% confidence intervals (CIs) were used to display the findings. Results: A
      prior miscarriage was associated with anxiety (adjusted OR (AOR) = 1.30; 95% CI:
      1.10-1.66) and depressive (AOR = 1.70; 95% CI: 1.21-2.39) symptoms at the 14-year
      follow-up. Having had a neonatal, infant and/or child deaths was associated with
      symptoms of depression at 14-year follow-up (AOR = 2.12; 95% CI: 1.06-4.25).
      Conclusion: The period after a child loss which involves a new pregnancy may be
      associated with relatively good mental health despite the fact that some mothers
      have experienced previous adverse pregnancy outcomes.

PMID- 29217938
TI  - Sociodemographic Correlates of HIV Discordant and Concordant Couples in Anambra
      State, Nigeria.
AB  - Background: The contribution of discordant partnerships to the burden of HIV/AIDS
      is significant. An understanding of the characteristics of HIV-affected couples
      will help modify preventive strategies. The aim of this study was to compare the
      HIV discordant and concordant partnerships for sociodemographic determinants in
      comprehensive health centers in Anambra State, Nigeria. Methods: This was an
      institution based case-control study of 289 (148 HIV-concordant and 141 HIV
      discordant) couples, selected using multistage sampling technique. Data
      collection was done through nterview using semi-structured questionnaire, while
      analysis was performed with Statistical Package for Social Sciences version 22.0.
      Chi-square and t tests were used to identify statistically significant
      associations between variables. Significance level was set at p value of <= 0.05.
      Results: There were more HIV-discordant positive males 83(28.6%) than females
      58(20.1%) (p = 0.043). The mean age (SD) of respondents was 37.8(9.8) years.
      Concordant couples tended to be younger than discordant couples, with differences
      in mean ages of 2.41 years (p = 0.028) for males and 2.87 years (p = 0.007) for
      females. There were no significant differences in proportion of remarriages (p =
      0.625) and type of marriage (p = 0.900). The majority of remarriages among
      discordant couples 15(65.2%), were due to divorce of previous spouses (p =
      0.054). Conclusions: This study found that there were more HIV positive males
      than females among discordant couples; females in discordant relationships were
      generally younger than their concordant counterparts. Concordant couples tended
      to be younger than discordant couples. Such knowledge should be factored in
      designing novel couple-targeted preventive strategies.

PMID- 29217939
TI  - Client-Centeredness of Family Planning Services in a Resource Limited Setting.
AB  - Background: Clients' needs and their satisfaction are priority issues in studying
      quality in reproductive health services. However, only 24-37% of Ethiopian women
      were informed about the available family planning methods and their utilization.
      High national total fertility rate (4.8) and low contraceptive prevalence rate
      (29%) might be attributed to these and other reasons. This study assessed the
      level of client-centeredness of family planning services and their determinants
      in public health facilities of Bahir Dar Town, Northwest Ethiopia. Methods: Exit
      interviews of 326 consecutively enrolled clients were conducted using structured
      questionnaire. Thirty consultation sessions were observed using a checklist to
      record client-provider interaction. The outcome variable was client centeredness
      as measured by perceived informed choice with perceived client-provider
      interaction as the intermediate variable. Results: The average levels of
      perceived informed choice and client provider interaction were 70.0% and 67.6%,
      respectively. Perceived clinical competence of providers, perceived integration
      and coordination of care, perceived accessibility of services, perceived
      participation of families and friends in care delivery, perceived physical
      comfort of the facilities and type of the health facility were the independent
      predictors of perceived client provider interaction. Perceived degree of client
      provider interaction, perceived clinical competence of providers, type of health
      facility and perceived accessibility of services were independent predictors of
      perceived informed choice (p<=0.01). Conclusion: Client-centeredness of family
      planning services, as measured by clien-provider interaction and informed choice
      was not sufficiently assured in the study facilities.

PMID- 29217940
TI  - Audit of Oral Histopathology Service at a Nigerian Tertiary Institution over a 24
      Year Period.
AB  - Background: Biopsies are often essential for definitive diagnosis of oro-facial
      lesions and are a part of oral diagnostic procedures carried out in
      histopathology laboratories. At present, there is paucity of literature on the
      audit of oral histopathology services in Nigeria. The objectives of this study
      were to determine the prevalence of biopsied oral lesions in a Nigerian tertiary
      institution. Also to profile the usage of oral pathology service and to identify
      challenges that may be present in an oral histodiagnostic service. Methods: This
      was a retrospective study performed at the Oral Pathology Department of the
      University of Ibadan/ University College Hospital, Ibadan, Nigeria. Reports of
      all biopsies submitted at the Oral Pathology laboratory, for the period 1990
      2014, were reviewed and data extracted. Descriptive analysis was done using SPSS
      software, version 20. Results: The total number of reports was 1,998; invalid
      reports constituting 220(11%) were subsequently excluded leaving 1,778(89%) valid
      reports. The mean age of patients was 36.70+/-19.79, while the peak age of
      presentation was in the 3rd decade. Male to female ratio was 1:1.1, and the
      mandible was the most common site of lesions 619(34.8%). These services were
      mainly utilized by oral surgeons (83.9%) and ameloblastoma (11.5%) was the most
      frequently diagnosed lesion. CD45 (16.7%) was the most frequently requested
      immuno-diagnostic test. Conclusion: Biopsied oral lesions were more prevalent in
      females, while oral and maxillofacial surgeons utilized these services the most.
      Inadequate biopsy specimens or unrepresentative specimens and deficient
      documentation were challenges identified in this study.

PMID- 29217941
TI  - Intestinal Obstruction in Early Neonatal Period: A 3-Year Review Of Admitted
      Cases from a Tertiary Hospital in Ethiopia.
AB  - Background: Failure to pass meconium by a full-term neonate within the first 24
      hours should raise a suspicion of bowel obstruction. The objective of this study
      was to determine pattern of presentation, diagnosis and outcome of management of
      intestinal obstruction in the early neonatal period in the Neonatal Care Unit of
      Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. Methods:
      Retrospective chart review of admitted cases from January 2011 to December 2013
      was done. Data were entered into SPSS software version 20. Descriptive analysis
      of data were done at first; then cross tabulation of variables with chi-square
      tests were done. Results: Fifty-one (41 males and 10 females) cases of neonatal
      intestinal obstructions were described. ARM was the most common type of
      intestinal obstruction followed by intestinal atresia and Hirschsprung's
      disease.Delayed diagnosis of cases was observed in 72%. Associated congenital
      anomalies were documented in 13 % of the cases. Death occurred in 20% of the
      cases. One or another form of infection accounted for 90% of the deaths. Neonatal
      sepsis and being unfit for anesthesia were determinants of mortality with p-value
      <0.02 and < 0.0007 respectively. Conclusion: Anorectal malformation is the
      commonest cause of early neonatal obstruction followed by small intestinal
      atresia and Hirschsprung's disease. Low number of associated anomalies has been
      reported. High rate of death due to preventable causes such as sepsis is
      observed. Delayed diagnosis of cases were also prevalent.

PMID- 29217942
TI  - The Association between Fruit and Vegetable Intake and Liver Enzymes (Aspartate
      and Alanine Transaminases) in Tehran, Iran.
AB  - Background: Intake of fiber and antioxidants and following hypocaloric diets has
      beneficial effects on reduction of the liver enzymes. Fruits and vegetables are
      low in calorie and rich in fiber and antioxidants. There are few studies about
      special dietary effects on liver function. The aim of this study was to evaluate
      the association between fruit and vegetables intake and liver function enzymes.
      Methods: This cross-sectional study was conducted on 265 Tehrani healthy adults.
      Fruit and vegetable intake was assessed by a 147-items semi-quantitative food
      frequency questionnaire. Serum glucose, lipids, liver enzymes (alanine
      aminotransferase (ALT), aspartate aminotransferase (AST)), hs-Crp and body
      composition were measured in a fasting state. Results: The mean age (+/- SD) of
      the participants was 35 +/- 8.78. In the higher quartiles of vegetable intake,
      low-density lipoprotein (LDL) serum and total cholesterol (TC) levels were lower
      after adjusting for confounders (p = 0.03 and 0.02 respectively). Individuals in
      the upper quartile of vegetable intake were less likely to have elevated ALT
      (OR=0.21; 95% CI =0.08-0.49) and AST (OR=0.33; 95% CI =0.15-0.75) levels before
      adjusting for confounders. After controlling for potential confounders, only the
      association between vegetable intake and ALT level remained significant (OR=0.32;
      95% CI =0.12-0.90). Liver enzymes had no significant relationship with the
      quartiles of fruit intake. In the higher quartiles of fruit intake, the visceral
      fat rating was lower after adjustment (p = 0.04) but not in the higher vegetable
      intake (p = 0.50). Conclusions: The results of this study showed that vegetable
      intake is reversely associated with LDL, TC and ALT level in Tehrani healthy
      adults, whereas fruit intake is only associated with lower visceral fat rating.

PMID- 29217943
TI  - Intestinal Parasitosis and Their Associated Factors among People Living with HIV
      at University of Gondar Hospital, Northwest-Ethiopia.
AB  - Background: Most HIV clients die of AIDS related intestinal parasitic infections
      rather than due to the HIV infection itself. Therefore, this study was aimed at
      determining the prevalence of intestinal parasite and their associated factors
      among HIV/AIDS clients at the University of Gondar Hospital, Northwest Ethiopia.
      Methods: Institution based cross sectional study was conducted using systematic
      random sampling technique from March to May 2016. A semi-structured questionnaire
      was used to collect data. Stool samples were collected and processed using direct
      wet mount, formol-ether concentration and modified Ziehl-Neelson staining
      techniques. Besides, blood samples were collected for CD4+ count estimation. Both
      descriptive and logistic regression analyses were used in data analysis. P-values
      <0.05 were considered as statistically significant. Results: A total of 223
      participants were enrolled in this study, and the prevalence of intestinal
      parasitosis was found to be 29.1%. The most predominant intestinal parasite
      detected was cyst of Entamoeba histolytica (8.5%) followed by Ascaris
      lumbricoides (6.7%), Strongyloides sterocoralis (3.6%) and Cryptosporidium parvum
      (3.1%), whereas Schistosoma mansoni (0.9%) and Hymenolepis nana (0.9%) were the
      least detected. Absence of toilet (AOR= 19.4, CI: 6.46-58.3), improper hand
      washing before meal (AOR=11.23, 95% CI: 4.16-30.27 and CD4+ count < 200 cells/mm3
      (AOR=33.31, 95% CI: 9.159-121.149) had significant association with prevalence of
      intestinal parasites. Conclusion: The study indicated that intestinal parasites
      are still a problem among HIV/AIDS patients in the study area. Thus, routine
      examination for intestinal parasites and interventions should be carried out for
      better management of clients.

PMID- 29217944
TI  - Analysis and Economic Implication of X-Ray Film Reject in Diagnostic Radiology
      Department of Jimma University Specialized Hospital, Southwest Ethiopia.
AB  - Background: Patients usually undergo repeated X-ray examinations after their
      initial X-ray radiographs are rejected due to poor image quality. This subjects
      the patients to excess radiation exposure and extra cost.It is therefore
      investigating the magnitude and causes of reject is mandatory. This study aimed
      to assess the reject rate of X-ray films and its economic implication in order to
      obtain information for further recommendations on image quality, cost and
      radiation exposure. Method: A cross-sectional study approaches was employed.
      Reject rate was measured for two x-rays in the department across all plain x-ray
      films examinations using a structured format on which relevant data for reject
      were recorded by investigators. The results were then collected and entered into
      a database for analysis. Result: Reject rate and cause of reject were measured
      across all plane x-ray examinations for the hospital. From a total of 6563
      exposed films, 16.85% were rejected. This leads to economic waste of 24,721.99
      ETB, or 17.8% of a total cost in 4month period and increase in radiation dose to
      both patients and staff. Conclusion: The findings from this study show that both
      the overall reject rate and individual reject rate were higher than the accepted
      range which could be due to machine fault, operator's technical limitations, or
      absence of quality control program in the department. We recommend that regular
      quality assurance and quality control procedure which are well documented should
      be established in the department.

PMID- 29217945
TI  - A 3-Year Review of the Outcome of Pars Plana Vitrectomy for Dropped Lens
      Fragments after Cataract Surgery in a Tertiary Eye Hospital in Dhaka, Bangladesh.
AB  - Background: Dropped lens fragments into the vitreous are uncommon, but
      potentially sight threatening complications of cataract surgery. The recommended
      approach for removal of dropped lens matter is pars plana vitrectomy with or
      without ultrasonic emulsification with the fragmatome. This study aimed to
      determine the visual outcome following pars plana vitrectomy for dropped lens
      fragments complicating cataract surgery at 6 weeks, 3 months and 6 months.
      Methods: This study is a retrospective review of patients who had PPV as
      treatment for dropped lens fragments complicating cataract surgery at Ispahani
      Islamia Eye hospital and Institute. The case notes of all patients who had PPV
      for dropped nucleus from January 2013 to December 2015 were reviewed. Information
      retrieved included the bio-data of the patients, clinical features such as visual
      acuity, intraocular pressure, cornea clarity, presence of anterior chamber
      activity, Lens status and fundus findings at presentation, 6 weeks, 3 months and
      6 months post surgery. Details of intra ocular procedure (Cryotherapy, Endo
      laser, Silicon oil or gas tamponade) in addition to PPV were noted. Result:
      Thirty-two cases were reviewed within the 36-month time period. There were 8(25%)
      females and 24(75%) males. Male to female ratio was 1:3. The best corrected
      visual acuity of patients at presentation was better than or equal to 6/60 in
      56.3% of the patients. Dropped nucleus occurred during phacoemulsification
      cataract surgery in the majority (59.6%) of the patients. The best corrected
      visual acuity was 6/18 or better in 10(31.3%) eyes at 6 months post-surgery.
      Worsening of visual acuity to light perception occurred in 3(9.4%) eyes at 6
      months, and 3 eyes (9.4%) developed phthisis bulbi. Conclusion: Modest
      improvement in visual acuity can be achieved after dropped nucleus complicating
      cataract surgery by Pars plana vitrectomy and removal of dislocated lens
      fragment.

PMID- 29217946
TI  - Association of Helicobacter Pylori with Presence of Myocardial Infarction in
      Iran: A Systematic Review and Meta-Analysis.
AB  - Background: Over the past decade, cardiovascular diseases have been recognized as
      the leading cause of mortality worldwide. Myocardial infarction (MI) is one of
      the most prevalent types of cardiovascular diseases that is caused by the closure
      of coronary arteries and ischemic heart muscle. Numerous studies have analyzed
      the role of H. pylori as a possible risk factor for coronary artery diseases, in
      most of which the role of infection in coronary artery disease is not
      statistically significant. Methods: These contradictory findings made us conduct
      a systematic review to analyze all relevant studies in Iran through a meta
      analysis and report a comprehensive and integrated result. All published studies
      from September 2000 until September 2016 were considered. Using reliable Latin
      databases like PubMed, Google Scholar, Google search, Scopus, Science Direct and
      Persian databases like SID, Irandoc, Iran Mede and Magiran. After quality
      control, these studies were entered into a meta-analysis by using the random
      effects model. After evaluating the studies, 11 papers were finally selected and
      assessed. Results: A total of 2517 participants had been evaluated in these
      studies, including 1253 cases and 1264 controls. Based on the results of meta
      analysis and using random effects model, an overall estimate of OR Helicobacter
      Pylori with Presence of Myocardial Infarction in Iran was OR=2.53 (CI=1.37-4.67).
      Conclusions: The results of this review study show that H. pylori are associated
      with the incidence of MI so that the odds ratio of MI in the patients with
      helicobacter pylori is twice greater than that of the people without H. pylori.
      Future studies are recommended to evaluate the mechanisms associated with
      relation of H. pylori with MI as well as its association with time.

PMID- 29217947
TI  - Coexistence of Peripheral Spondyloarthritis and Familial Adenomatous Polyposis: A
      Rare Case Report with Treatment Contradictions and Review of the Literature.
AB  - Background: The coexistence of familial adenomatous polyposis and
      spondyloarthritis is rarely defined in literature. The primary aim of this
      presentation is to report a development of peripheral arthritis in 3 years
      following colon surgery with the diagnosis of familial adenomatous polyposis
      (FAP). The secondary aim is to discuss the challenge of in treatment of
      refractory arthritis, which needs to be treated with biologics. However, it is
      not yet known well about their safety on patients who have risks for cancer
      development. Case Details: A 25-year-old female patient was admitted to the
      rheumotology outpatient clinic. The patient had undergone total colectomy and
      ileoanal anastomosis because of FAP three years ago. On her physical examination,
      there was arthritis on her left ankle and enthesitis on both Achilles tendons.
      Conclusion: This case report presents a 25-year-old female patient with
      Ankylosing spondylitis (AS) and FAP whose treatment with biologics is critical
      due to the risk of cancer development due FAP. Although the potential risk of
      development of malignancies with TNF-blocking therapy seems to be no more than
      TNF-naive patients and general population. But the safety of these drugs on
      patients with risks for cancer development is still unknown.

PMID- 29217948
TI  - Is the Malaria Elimination Target Achievable?

PMID- 29217949
TI  - The Effect of Psychosocial Factors and Patients' Perception of Tuberculosis
      Treatment Non-Adherence in Addis Ababa, Ethiopia.
AB  - Background: Although there are several studies reported on factors affecting
      tuberculosis (TB) treatment non-adherence, there is information gap on
      psychosocial and patients' perceptions aspects. Therefore, this study was aimed
      to investigate the effect of psychosocial factors and patients' perceptions on TB
      treatment non-adherence in Ethiopia. Methods: A cross sectional study was
      conducted in Addis Ababa from May to December, 2014. Thirty one health facilities
      were randomly selected and 698 TB patients, who had been on treatment, were
      enrolled consecutively using patient registration number. Structured
      questionnaire was used to collect data on demographics, knowledge, psychological
      distress, alcohol use, tobacco smoking and six HBM domains. Treatment adherence
      level was the main outcome variable, and it measured using visual analog scale.
      Statistical Package for Social Sciences version 20 was used for data analysis.
      Results: Non-adherence level within last one month prior to the study was 19.5%.
      After controlling for all potential confounding variables, Antiretroviral Therapy
      (ART) status (Adjusted Odds Ratio (AOR) = 1.79, 95% Confidence interval (CI)
      (1.09 -2.95)), alcohol use (AOR = 2.11, 95% CI (1.33-3.37)), economic status (AOR
      = 0.53, 95% CI (0.33-0.82)), perceived barriers (AOR = 1.21, 95% CI (1.10-1.47))
      and psychological distress (AOR = 1.83, 95% CI (1.47-2.29)) were independently
      associated with TB treatment non-adherence. Conclusion: ART status, economic
      status, alcohol use, perceived barrier and psychological distress are the major
      areas that need to be targeted with health promotion intervention to enhance TB
      treatment adherence.

PMID- 29217950
TI  - Agreement between Direct Fluorescent Microscopy and Ziehl-Neelsen Concentration
      Techniques in Detection of Pulmonary Tuberculosis in Northwest Ethiopia.
AB  - Background: The sensitivity of smear microscopy for diagnosis of tuberculosis
      might be improved through treatment of sputum with sodium hypochlorite and
      application of fluorescent microscopy. This study aimed to determine the
      agreement between direct Fluorescent Microscopy and Ziehl-Neelsen concentration
      technique by their ability of detecting acid fast bacilli in resource poor
      settings. Methods: A cross sectional study was conducted at Gondar University
      Referral Hospital, Northwest Ethiopia. Three sputum specimens were collected from
      consecutive TB suspects. Direct and concentrated sputum smears were air-dried,
      heat-fixed and stained by auramine O and Ziehl-Neelsen staining techniques
      respectively. The stained slides were examined for acid fast bacilli using direct
      Fluorescent Microscopy and Ziehl-Neelsen concentration techniques. Results: Of
      293 specimens, 4.4% and 2.4 % were AFB positive by direct fluorescent microscopy
      and Ziehl-Neelsen bleach concentrated techniques respectively. There was high
      percentage of tuberculosis positivity from early morning sputum samples (2.4%)
      compared to first spot (1.4%) and second spot (1.7%) sputum samples when using
      Ziehl-Neelsen sodium hypochlorite concentration technique. A moderate agreement
      was seen between the two methods (Kappa=0.484, P value<0.001). Conclusion: Direct
      fluorescent microscopy has shown high positivity rate compared to Ziehl-Neelsen
      concentration technique. A moderate agreement was seen between the two methods.
      Thus, Ziehl-Neelsen bleach sedimentation technique is recommended for detection
      of pulmonary tuberculosis at peripheral health service level when Fluorescent
      Microscopy is not available.

PMID- 29217951
TI  - Five Years Malaria Trend Analysis in Woreta Health Center, Northwest Ethiopia.
AB  - Background: An estimated 68% of the Ethiopian population, living in 75% of the
      landmass, is at risk of contracting malaria at any time making it the leading
      public health problem. The temporal analysis of malaria data could be important
      to evaluate the performance of malaria prevention programmes. Thus, the aim of
      this study was to determine the trend of malaria at Woreta Health Center (WHC)
      over a period of five years. Methods: We analyzed the records of 8,057
      presumptive malaria patients registered in 2012 to 2016. The following patient
      data were retrieved from laboratory registration logbook for analysis: sex, age,
      residence, blood film (BF) microscopy result, type of malaria parasite
      identified, year and month when the patients visited WHC. Logistic regression was
      employed to assess the association between potential associated factors and
      positive BF result; p < 0.05 was considered significant. Results: Among the total
      presumptive individuals, 4447(55.2%) were females. The prevalence of malaria in
      each year ranged from 4.1% to 6.7%. The overall prevalence of malaria was 5.4%
      (95%CI: 4.9%-5.9%). The two most important species of malaria parasite identified
      were P. falciparum at 233(53.7%) and P. vivax at 184(42.4%). Relatively higher
      proportions of cases were documented in the months of November, December and June
      (11.1%, 8.1% and 7.2%, respectively). Patients who visited the health center in
      the month of December were >4 times more likely to be infected as compared with
      those who came to the health center in September [AOR: 4.2, 95%CI (2.374-7.560)].
      Females were 1.3 times more likely to be infected than males, [AOR: 1.3, 95%CI
      (1.101-1.638)]. Similarly, patients in the age group above 15 were 1.9 times more
      likely to be infected than individuals < 5, [AOR: 1.9 95%CI (1.498-2.455), p
      value 0.000]. Conclusion: In the studied area, malaria remains a major public
      health challenge. Hence, interventions to decrease the impact of the disease have
      to be evaluated and strengthened.

PMID- 29217952
TI  - Control of Hypertension among Diabetic Patients in a Referral Hospital in
      Tanzania: A Cross-Sectional Study.
AB  - Background: Hypertension is common among diabetic patients. The co-existence of
      two conditions carries an excessive risk of severe complications and mortalities.
      Limited information exists on the determinants of poor hypertension control among
      these patients. We aimed at determining the prevalence and factors associated
      with poor hypertension control in these patients. Methods: Data of diabetic
      patients who were also hypertensive attending an outpatient clinic from 1 August
      2015 to 31 December 2015 at Bugando Medical Centre were retrospectively analyzed.
      Uncontrolled hypertension was defined as a blood pressure of >=130mmHg and/or
      >=80mmHg systolic and diastolic respectively. A designed questionnaire was used
      to collect data of patients. Continuous variables were summarized by median and
      interquartile ranges (IQR) and categorical variables were summarized by frequency
      and percentage. Logistic regression was used to find the predictors of
      uncontrolled hypertension. Results: The majority of our study population were
      females, 161/295 (54.6%), and the median age was 57 years (IQR 50-64). The
      prevalence of hypertension was 206/295 (69.8%). A total of 174/206 (84.5%)
      patients had uncontrolled hypertension. This poor control was significantly
      associated with poor adherence to anti-hypertensives (OR 1.73[1.26-2.38]
      p=0.002), presence of any long-term complication (OR 3.19 [1.65-6.18] p=0.03) and
      overweight (BMI>24.9 Vs <24.9) (OR 1.68 [0.98-2.88], p=0.04). Under-prescription
      and ambiguous drugs combination was also observed. Conclusion: The prevalence of
      poor hypertension control among diabetic patients in Tanzania is alarming. Most
      of the factors associated with this situation can be modified. The clinicians
      should advocate individualized management, continuous health education and
      adherence to the available guidelines.

PMID- 29217953
TI  - Assessment of Pediatrics Radiation Dose from Routine X-Ray Examination at Jimma
      University Hospital, Southwest Ethiopia.
AB  - Background: Given the fact that children are more sensitive to ionizing radiation
      than adults, with an increased risk of developing radiation-induced cancer,
      special care should be taken when they undergo X-ray examinations. The main aim
      of the current study was to determine Entrance Surface Dose (ESD) to pediatric
      patients arising from routine x-ray examination in the Radiology Department of
      Jimma University Specialized Hospital (JUSH). Methods: Descriptive cross
      sectional study was conducted on pediatric patients less than 15 years of age who
      visited to seek x-ray examinations in JUSH. In this study, chest (AP), skull
      (AP), Abdomen (AP) and Pelvic (AP) x-ray examinations were analyzed. Radiographic
      exposure factors were recorded in each examination. ESD was calculated using
      exposure parameters. The calculated ESD values were weighed against the
      Diagnostic Reference Level (DRL) recommended doses and similar published studies.
      Comparison was made among different age groups through mean comparison. Result:
      The obtained ESD values were mostly higher than the values in internationally
      published studies and DRL for all age groups. For chest AP, the mean ESD values
      were 1.82mGy which is higher than similar studies in Nigeria (0.642Mgy), Brazil
      (o.o62mGy) and NRPB (0.050mGy) for ages of 0-1 years. Conclusion: The higher
      pediatric patient dose obtained in this study is a further indicator that doses
      delivered to pediatric patients are not according to ALARA principle, and there
      is a need to optimize service and patients' radiation exposure in JUSH in
      particular and in Ethiopia in general.

PMID- 29217954
TI  - The Barriers to Achieve Financial Protection in Iranian Health System: A
      Qualitative Study in a Developing Country.
AB  - Background: The move to universal health coverage and consequently health
      promotion is influenced by political, socio-economic and other contextual factors
      in a country. Iran, as a developing country with an upper-middle national income,
      has developed policies to achieve universal health coverage through financial
      protection. This study aims to investigate barriers to develop financial
      protection as a requirement to achieve universal health coverage. Materials and
      Methods: This qualitative study was conducted using 20 in-depth interviews with
      experts in social welfare, health insurance and financing. The framework analysis
      method was used to analyze the data. Results: The results have been categorized
      in three major themes that were extracted from ten sub-themes. The major themes
      included the political, social and economic context of the country, the context
      and structure of healthcare system and dimensions of UHC. Conclusion: Achieving
      financial protection as a long-term objective should be considered as a priority
      among Iranian policy makers that requires an inter-sectoral collaboration with a
      defined in-charge body. Health policy makers in Iran should develop a more
      comprehensive benefits package for diseases and health conditions with
      catastrophic consequences. They also should develop a plan to cover the poor
      people.

PMID- 29217955
TI  - Determinants of Podoconiosis, a Case Control Study.
AB  - Background: Podoconiosis is a non-filarial swelling of lower extremity endemic in
      tropical regions, North America and India. The etiology and pathophysiology of
      the disease remain unknown. The objective of this study was to identify the
      determinants of Podoconiosis. Methods: Unmatched case control study design was
      conducted. The sample size was calculated using Epi-info soft ware: 95% CI, 85%
      power, control to case ratio of 2:1, expected frequency of barefoot among
      controls 50%, odds ratio of 1.5 and non-response rate of 10% yielding 1148 study
      participants. Binary logistic regression was used to identify the determinants of
      Podoconiosis. Results: A total of 1113 study participants (379 cases and 734
      controls) were included giving for a response rate of 96.95%. Positive family
      history (AOR, 2.81 [95% CI: 1.7-4.64]), bare foot (AOR, 3.26 [95% CI: 2.03
      5.25]), poor foot hygiene (AOR, 2.68 [95 CI: 1.72 - 4.19]) increase the risk of
      Podoconiosis. Female gender (AOR, 0.26 [95% CI: 0.15-0.44]), good housing
      condition (AOR, 0.17 [95% CI: 0.1-0.3]), medium income (AOR, 0.12 [95 % CI: 0.07-
      0.22]) and primary education (AOR, 0.02 [95% CI: 0.01-0.04]) decrease the risk of
      Podoconiosis. Conclusion: Podoconiosis control and prevention programmes should
      involve the low income and uneducated populations.

PMID- 29217956
TI  - Utilization Status of Electronic Information Sources (EIS) for HIV/AIDS Care and
      Treatment in Specialized Teaching Hospitals of Ethiopia, 2016.
AB  - Background: According to the World Health Organization, the use of Electronic
      Information Sources (EIS) in healthcare is not merely about application of
      technology, but it is also a foundation to provide higher quality clinical care.
      This study was aimed to assess Utilization Status of EIS for HIV/AIDS Care and
      Treatment in specialized teaching hospitals of Ethiopia, 2016. Materials and
      Methods: A facility based cross-sectional study design was used. The study
      populations were 352 healthcare professionals selected by using simple random
      sampling technique from three randomly selected specialized teaching hospitals of
      Ethiopia. Quantitative and qualitative data were collected and analyzed by
      fitting multivariate logistic regression model and thematically by bringing
      similar themes together respectively. Results: This study revealed that only
      33.2% of the health professionals used EIS as supporting tool in their clinical
      practice including HIV/AIDS care and treatment. The main reasons for not using
      EIS were having no training 285(89.9%), followed by preferring print resources
      20(6.3 %). Furthermore, there was statistically significant association between
      use of EIS and perceived electronic information retrieval skills AOR = 3.271, CI
      (1.942, 4.051), perceived quality of electronic information content retrieved
      AOR= 2.069, CI (1.051, 3.925) and limited access to computer and internet
      connection AOR = 5.072, CI (1.834, 5.931). Conclusions: In this study, only one
      third of health professionals used EIS as supporting tool in their clinical
      practice. Hence, hospital boards should devise strategies to improve utilization
      of EIS.

PMID- 29217957
TI  - Evaluation of Parasitological Methods for the Detection of Strongyloides
      Stercoralis among Individuals in Selected Health Institutions In Addis Ababa,
      Ethiopia.
AB  - Background: Strongyloides stercoralis causes chronic intestinal infection that
      may lead to disseminated disease during immunosuppression. Therefore, efficient
      diagnostic methods are essential to detect silent and latent infections. The
      present study was aimed to compare the efficacy of parasitological methods for
      the detection of S. stercoralis infection. Methods: A cross-sectional study was
      conducted on 351 subjects (226 HIV positive and 125 HIV negative) from October
      2005 to May 2006. The study participants were selected by systematic random
      sampling method. Fresh fecal samples were collected from each participant and
      processed by different parasitological methods. Results: Among the 351
      individuals involved in the study, 43(12.3%) were infected by S. stercoralis. The
      prevalence of S. stercoralis infection was significantly higher among HIV
      positive subjects (17.3%) as compared with 3.2% in HIV negative subjects
      (p=0.001). The odd of being infected by S. stercoralis was significantly higher
      among AIDS patients (OR=6.31; 95% CI, 2.2-18.1) and HIV patients with diarrhea
      (OR=9.3; 95% CI 4.6-18.9) as compared with respective controls. Agar plate
      culture showed superior sensitivity (97.7%) than other methods for detection of
      S. stercoralis. Similarly, agar plate culture showed strong diagnostic agreement
      with Baermann's method (kappa = 0.82; 95% CI 0.72 - 0.92) followed by fecal
      concentration (kappa= 0.67; 95% CI=0.54-0.80). Coclusion: This study revealed
      that HIV patients were about 6 folds susceptible for S. stercoralis infection.
      Similarly, agar plate culture showed superior diagnostic efficiency for
      detections of S. stercoralis infection.

PMID- 29217958
TI  - Assessment of Barriers to Reproductive Health Service Utilization among Bench
      Maji Zone Pastoralist Communities.
AB  - Background: The reproductive health (RH) needs and challenges in pastoralist area
      are different from elsewhere. People in this area live in very traditional
      settings and adhere strongly to traditional cultural values and beliefs. Some of
      these beliefs are known to lead to poor sexual and RH outcomes. Thus, the
      objective of the study was to identify barriers of RH service utilization among
      pastoralist communities of Bench Maji zone. Methods: This study was conducted in
      pastoralist communities of 5 woredas in Bench Maji zone. Qualitative study was
      conducted through FGD, IDI and KII. For this study 15 FGDs, 5 IDI and 5 KII were
      conducted. Recorded data was first transcribed in to local languages and
      translated to English by experts. The data was coded and themes were identified.
      Finally the result was presented narratively. Results: The major challenges of RH
      service utilization identified in this study were preference of female
      professionals, preference of home delivery, cultural influences, lack of
      knowledge, decision maker related barriers, and health facility related barriers.
      Husband disapproval was significant challenge for utilization of services. Family
      disapproval for adolescent RH service utilization and judgmental approach of
      health professionals for contraceptive utilization were also common barriers.
      Conclusions: Preference of female professionals, preference of home delivery,
      cultural influences, lack of knowledge, decision maker barrier, and health
      facility related barriers were identified barriers. Therefore, awareness creation
      to the community, and capacity building to health professionals are recommended.

PMID- 29217959
TI  - Periodontal Therapy with 0.25%Lemongrass Oil Mouthwash in Reducing Risk of
      Cardiovascular Diseases: A 3-Arm Prospective Parallel Experimental Study.
AB  - Background: Periodontal disease is associated with cardiovascular diseases
      because of its role in host immune-inflammatory response. Serum lipids are the
      commonest risk factors between periodontal disease and cardiovascular diseases.
      Materials and Method: A double blinded randomised clinical trial was carried out
      among 45 subjects with generalised severe periodontitis. They were divided into 3
      groups of 15 subjects each. Group A: 0.25% lemongrass oil mouthwash, Group B:
      0.12% chlorhexidine mouthwash and Group C: Oral prophylaxis only Group. Oral
      examinations like assessment of Probing Pocket Depth and Clinical Attachment Loss
      and Bio-chemical tests like assessment of C-Reactive Protein, Total Cholesterol,
      High Density Lipid, Low Density Lipid and triglycerides were conducted at
      baseline followed by oral prophylaxis at the same visit. Reassessment of the
      above mentioned parameters were done after 3 months of intervention. Data so
      collected were subjected for statistical analysis using SPSS ver. 20.0. Results:
      A statistically significant reduction in C-Reactive Protein, Probing Pocket
      Depth, Clinical Attachment Loss, Total Cholesterol and Low Density Lipid level in
      0.25% lemongrass oil mouthwash group was found. On comparing a statistically
      significant difference was observed for the post intervention scores of Probing
      Pocket Depth and Clinical Attachment Loss only; for Group A v/s C and Group B v/s
      C. Conclusion: 0.25% Lemongrass oil mouthwash was found to be a good herbal
      alternative; both in the treatment of chronic periodontitis and reduction in the
      level of serum markers of Cardio Vascular Diseasess.

PMID- 29217960
TI  - Knowledge Management Implementation and the Tools Utilized in Healthcare for
      Evidence-Based Decision Making: A Systematic Review.
AB  - Background: Healthcare is a knowledge driven process and thus knowledge
      management and the tools to manage knowledge in healthcare sector are gaining
      attention. The aim of this systematic review is to investigate knowledge
      management implementation and knowledge management tools used in healthcare for
      informed decision making. Methods: Three databases, two journals websites and
      Google Scholar were used as sources for the review. The key terms used to search
      relevant articles include: "Healthcare and Knowledge Management"; "Knowledge
      Management Tools in Healthcare" and "Community of Practices in healthcare".
      Results: It was found that utilization of knowledge management in healthcare is
      encouraging. There exist numbers of opportunities for knowledge management
      implementation, though there are some barriers as well. Some of the opportunities
      that can transform healthcare are advances in health information and
      communication technology, clinical decision support systems, electronic health
      record systems, communities of practice and advanced care planning. Conclusion:
      Providing the right knowledge at the right time, i.e., at the point of decision
      making by implementing knowledge management in healthcare is paramount. To do so,
      it is very important to use appropriate tools for knowledge management and user
      friendly system because it can significantly improve the quality and safety of
      care provided for patients both at hospital and home settings.

PMID- 29217961
TI  - Clinical Profile and Outcome of Pediatrics Tetanus: The Experience of a Tertiary
      Hospital in Ethiopia.
AB  - Background: Tetanus is an acute vaccine preventable illness manifested by
      neuromuscular dysfunction due to a potent exotoxin, tetanospasmin produced by
      Clostridium tetani. It is a common health problem in developing countries like
      Ethiopia. The aim of this study was to assess clinical profile and outcome of
      Pediatrics tetanus in a referral hospital, South Ethiopia. Methods: This is a
      retrospective cross-sectional study of medical records of 24 Pediatric tetanus
      patients who were admitted from July 2014 to June 2016 to the Pediatrics
      Department of Hawassa University Comprehensive Specialized Hospital, Hawassa
      Ethiopia. Tetanus was diagnosed clinically. Data were entered and analyzed using
      SPSS statistical software. Results: The median age at diagnosis was 8 years with
      19 (79.2%)of the study subjects being males. There were 3 male neonatal tetanus
      cases with 2 deaths. From post-neonatal cases, only 8(38.1%) were fully
      vaccinated for infant Expanded Period of Immunization (EPI). Booster vaccination
      with TT (tetanus toxoid) was only given to 5(29.4%) of discharged patients.
      Trauma was common in above 5 years of age and documented in 19(79.2%) of
      patients. All tetanus cases were generalized type with mild, moderate and severe
      grades comprising 7(29.2%), 8(33.3%), 7(29.2%) and 2(8.3%) respectively. Case
      fatality rate was 29.2% (7) with more deaths in higher grades. Respiratory
      failure 6(85.7%), and aspiration pneumonia 1(14.3%) were causes of death.
      Conclusion: In this study, case fatality rate was high. Hence, health promotion
      with scale-up of EPI for infant tetanus immunization and large scale studies to
      provide support for booster vaccination schedules are recommended.

PMID- 29217962
TI  - Spectrophotometric Evaluation of Crown Fragment a Year After Reattachment Using
      Fiber-Reinforced Post: A Case Report.
AB  - Background: Crown fracture is the most common type of fracture and frequently
      affects the anterior teeth. Crown fractures have been treated in several ways
      depending on the location and kind of fracture. This case emphasizes reattachment
      of fractured fragments using fiber-reinforced post. Also this case report
      underlines the related aesthetic concerns of reattaching of the fractured
      fragment. Case Report: Intraorally, examination revealed a complicated crown-root
      fracture of the left maxillary central (#21) and lateral incisor (#22). Moreover,
      the incisal one-third of the right maxillary central incisor (#11) was fractured.
      Baseline color of the tooth was recorded with a spectrophotometer to compare
      final color of tooth treated with fiber post. The root canal of 21 and 22 was
      filled with a sealer and gutta-percha. Then, the fiber-reinforced post was placed
      into the canals, and fractured segments were bonded with self-adhesive resin
      cement. Direct composite resin restoration was applied to 11. A year later, a
      second color measurement was recorded, and color differences (DeltaE) were
      calculated. Result: In 12 months' follow-up, 11, 21 and 22 were asymptomatic with
      satisfying aesthetics, maxillar right incisor was vital. When crown discoloration
      was examined, there was clinically perceptible but acceptable discoloration
      without periapical pathology. Conclusion: Fiber reinforced post empowers not only
      the protection and reinforcement of tooth structure but also provides esthetic
      restoration.

PMID- 29217963
TI  - Penalized nonparametric scalar-on-function regression via principal coordinates.
AB  - A number of classical approaches to nonparametric regression have recently been
      extended to the case of functional predictors. This paper introduces a new method
      of this type, which extends intermediate-rank penalized smoothing to scalar-on
      function regression. In the proposed method, which we call principal coordinate
      ridge regression, one regresses the response on leading principal coordinates
      defined by a relevant distance among the functional predictors, while applying a
      ridge penalty. Our publicly available implementation, based on generalized
      additive modeling software, allows for fast optimal tuning parameter selection
      and for extensions to multiple functional predictors, exponential family-valued
      responses, and mixed-effects models. In an application to signature verification
      data, principal coordinate ridge regression, with dynamic time warping distance
      used to define the principal coordinates, is shown to outperform a functional
      generalized linear model.

PMID- 29217964
TI  - Sit Down and Play: A Preventive Primary Care-Based Program To Enhance Parenting
      Practices.
AB  - The primary care office offers an ideal setting to encourage parenting behaviors
      that promote early childhood development. We conducted a pilot study to establish
      feasibility and acceptability of Sit Down and Play (SDP), a brief primary care
      based program to facilitate positive parenting behaviors through take-home play
      activities. A prospective 1-month study was conducted in an urban primary care
      clinic. SDP was administered to 30 caregivers of 6-12 month old children while
      they waited for their well-child appointment. Caregivers completed baseline and 4
      week follow-up surveys. Open-ended interview questions regarding acceptability
      and usefulness of SDP were administered and analyzed using content analysis.
      Parenting practices related to child development were measured with standardized
      measures and changes analyzed using paired t-test and linear mixed effects
      models. Most caregivers were mothers (90%) and non-white (97%); the majority of
      children received Medicaid (87%). There were significant increases in parental
      reports of practices related to child development (p<0.001), including families
      who reported low incomes (i.e. <$25,000) and received a high-school education or
      less (p=0.001). Four main themes emerged from the open-ended interview data: 1)
      importance of play, 2) noticing a change in their child, 3) reinforcing existing
      positive parenting behaviors, and 4) satisfaction with the program. This
      preliminary study suggests that SDP is a feasible and potentially beneficial
      program that can be delivered during pediatric well-child visits. Further studies
      are needed to determine the effectiveness of SDP on parenting behaviors and
      developmental outcomes.

PMID- 29217966
TI  - LPV Modeling of a Flexible Wing Aircraft Using Modal Alignment and Adaptive
      Gridding Methods.
AB  - One of the earliest approaches in gain-scheduling control is the gridding based
      approach, in which a set of local linear time-invariant models are obtained at
      various gridded points corresponding to the varying parameters within the flight
      envelop. In order to ensure smooth and effective Linear Parameter-Varying
      control, aligning all the flexible modes within each local model and maintaining
      small number of representative local models over the gridded parameter space are
      crucial. In addition, since the flexible structural models tend to have large
      dimensions, a tractable model reduction process is necessary. In this paper, the
      notion of sigma-shifted [Formula: see text]- and [Formula: see text]-norm are
      introduced and used as a metric to measure the model mismatch. A new modal
      alignment algorithm is developed which utilizes the defined metric for aligning
      all the local models over the entire gridded parameter space. Furthermore, an
      Adaptive Grid Step Size Determination algorithm is developed to minimize the
      number of local models required to represent the gridded parameter space. For
      model reduction, we propose to utilize the concept of Composite Modal Cost
      Analysis, through which the collective contribution of each flexible mode is
      computed and ranked. Therefore, a reduced-order model is constructed by retaining
      only those modes with significant contribution. The NASA Generic Transport Model
      operating at various flight speeds is studied for verification purpose, and the
      analysis and simulation results demonstrate the effectiveness of the proposed
      modeling approach.

PMID- 29217965
TI  - Guidance for the Clinical Management of Thirdhand Smoke Exposure in the Child
      Health Care Setting.
AB  - Objective: To explain the concept of thirdhand smoke and how it can be used to
      protect the health of children and improve delivery of tobacco control
      interventions for parents in the child health care setting. Methods: Review of
      the literature and descriptive report. Results: The thirdhand smoke concept has
      been used in the CEASE intervention to improve the delivery of tobacco control
      counseling and services to parents. Materials and techniques have been developed
      for the child health care setting that use the concept of thirdhand smoke.
      Scientific findings demonstrate that thirdhand smoke exposure is harmful and
      establishes the need for clinicians to communicate the cessation imperative: the
      only way to protect non-smoking household members from thirdhand smoke is for all
      household smokers to quit smoking completely. As the scientific knowledge of
      thirdhand smoke increases, advocates will likely rely on it to encourage
      completely smoke-free places. Conclusion: Recent scientific studies on thirdhand
      smoke are impelling further research on the topic, spurring the creation of
      tobacco control policies to protect people from thirdhand smoke and stimulating
      improvements to the delivery of tobacco control counseling and services to
      parents in child health care settings.

PMID- 29217967
TI  - Tuning Properties of Poly(ethylene glycol)-block-poly(simvastatin) Copolymers
      Synthesized via Triazabicyclodecene.
AB  - Simvastatin was polymerized into copolymers to better control drug loading and
      release for therapeutic delivery. When using the conventional stannous octoate
      catalyst in ring-opening polymerization (ROP), reaction temperatures >=200 
      degrees C were required, which promoted uncontrollable and undesirable side
      reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base
      organocatalyst, was used as an alternative to polymerize simvastatin.
      Polymerization was achieved at 150  degrees C using 5 kDa methyl-terminated
      poly(ethylene glycol) (mPEG) as the initiator. ROP reactions with 2 kDa or 550 Da
      mPEG initiators were also successful using TBD at 150  degrees C instead of
      stannous octoate, which required a higher reaction temperature. Biodegradability
      of the poly(simvastatin) copolymer in phosphate-buffered saline was also
      improved, losing twice as much mass than the copolymer synthesized via stannous
      octoate. The three copolymers exhibited modified rates of simvastatin release,
      demonstrating tunablity for drug delivery applications.

PMID- 29217968
TI  - Investigation of markers of allergic sensitization and viral infections in
      children with allergy and asthma.
AB  - Background: Allergic diseases are the most prevalent chronic diseases in the
      developed countries. It is believed that early allergic sensitization and
      respiratory viral infections play an important role in the development of
      allergic diseases and asthma. Methods: The current study investigated the
      correlation between asthma, allergy, and various markers - allergen-specific IgE,
      IgG4 and IgA, ECP, IgM, and IgG antibodies against respiratory viruses hRSV and
      hPIV1-4 - in blood serum samples from 80 children (mean age 5.2 years) recruited
      from the Lithuanian birth cohort. Children were divided into three groups
      according to their diagnosis: asthma (n = 25), allergy without asthma (n = 14),
      and control group (n = 41). Results: Based on retrospective data, airway
      infections and bronchitis by the age of two years were associated with asthma in
      later childhood. The presence of IgM and IgG antibodies against hRSV and hPIV1-4
      at the age of five years were not associated with asthma and allergy: a high rate
      of persistent or past respiratory viral infections was revealed in all three
      groups. Among allergic children, increased levels of allergen-specific IgE and d1
      specific IgG4 were determined. Conclusion: The current study provides new
      insights into the relationships between allergic sensitization and respiratory
      virus infections in children.

PMID- 29217969
TI  - Severity of hyperoxia as a risk factor in patients undergoing on-pump cardiac
      surgery.
AB  - Background: Hyperoxia has long been perceived as a desirable or at least an
      inevitable part of cardiopulmonary bypass. Recent evidence suggest that it might
      have multiple detrimental effects on patient homeostasis. The aim of the study
      was to identify the determinants of supra-physiological values of partial oxygen
      pressure during on-pump cardiac surgery and to assess the impact of hyperoxia on
      clinical outcomes. Materials and methods: Retrospective data analysis of the
      institutional research database was performed to evaluate the effects of
      hyperoxia in patients undergoing elective cardiac surgery with cardiopulmonary
      bypass, 246 patients were included in the final analysis. Patients were divided
      in three groups: mild hyperoxia (MHO, PaO2 100-199 mmHg), moderate hyperoxia
      (MdHO, PaO2 200-299 mmHg), and severe hyperoxia (SHO, PaO2 >300 mmHg).
      Postoperative complications and outcomes were defined according to standardised
      criteria of the Society of Thoracic Surgeons. Results: The extent of hyperoxia
      was more immense in patients with a lower body mass index (p = 0.001) and of
      female sex (p = 0.005). A significant link between severe hyperoxia and a higher
      incidence of infectious complications (p - 0.044), an increased length of
      hospital stay (p - 0.044) and extended duration of mechanical ventilation (p <
      0.001) was confirmed. Conclusions: Severe hyperoxia is associated with an
      increased incidence of postoperative infectious complications, prolonged
      mechanical ventilation, and increased hospital stay.

PMID- 29217970
TI  - Recurrent pericarditis: a case report and literature review.
AB  - Background: Recurrence affects about 30% (20% to 50%) of patients within 18
      months after the initial episode of acute pericarditis resulting in subsequent
      rehospitalizations. Bearing in mind high treatment costs of patients admitted to
      hospital with acute and recurrent pericarditis, there is a need to optimize the
      treatment of both of these conditions. Materials and methods: We present a case
      of recurrent pericarditis. The first episode of pericarditis was diagnosed in
      2006. Three months later the patient was hospitalized due to clinical symptoms
      suggesting recurrence of a past condition. Ten years after the initial episode of
      acute pericarditis the patient was hospitalized for the treatment of recurrent
      pericarditis. The search for etiology of the disease was unsuccessful, the
      patient received treatment with nonsteroidal anti-inflammatory drugs; empiric
      antimicrobial therapy was also administered. Results and conclusions: Acute
      pericarditis is the most common disease of the pericardium encountered in
      clinical practice. Colchicine has been demonstrated as a first-line drug to be
      added to conventional anti-inflammatory therapies in patients with a first
      episode of pericarditis or its recurrences in order to improve the response to
      therapy and reduce recurrences. Despite a large amount of new data, there are
      still several issues that require additional research and clarification,
      including the search for new individualized therapies, the best duration of
      treatment for patients with pericardial diseases, and optimization of patient
      follow-up in order to collect data on long-term outcomes that would allow
      shortening the duration of in-patient treatment and reduction of recurrences.

PMID- 29217971
TI  - Evaluation of the relationship between the occlusion parameters and symptoms of
      the temporomandibular joint disorder.
AB  - Background: The aetiology of temporomandibular joint disorders (TMD) is
      multifactorial, whereas occlusal disharmony is one of the predisposing factors.
      Researchers still discuss the relation between occlusion and TMD. Objective: The
      study aims to investigate the relation between static occlusal parameters and TMD
      clinical symptoms using T-Scan II analysis system. Material and methods: The
      sample consisted of 44 persons divided into the treatment group of 20 TMD
      patients and the control group of 24 subjects without TMD. The main task of T
      Scan II computerized occlusal analysis system was to record every patient's
      occlusion and estimate static occlusal parameters: centre of occlusal force,
      asymmetry index of maximum occlusal force and occlusion time. These results were
      compared between groups, data related to patients' complaints and clinical
      symptoms. The analysis was carried out using Mann-Whitney U, Kruskal-Wallis and
      Chi-square tests. Results: Averages of the centre of occlusal force in TMD
      subjects were 6.55 +/- 0.99 mm, in the control group - 5.88 +/- 0.69 mm; the
      asymmetry index of maximum occlusal force averages: 15.90 +/- 2.71 and 12.93 +/-
      1.88; occlusion time: 0.281 +/- 0.036 s and 0.236 +/- 0.022 s, respectively.
      There were no statistically significant differences between two groups but they
      were found in the centre of occlusal force and the asymmetry index in the two
      groups (p < 0.05). Conclusions: There exists a relation between complaints of
      patients with TMD and static occlusion parameters. Values of the centre of the
      occlusal force distance and the asymmetry index of occlusal force in TMD patients
      with pain in the temporomandibular joint (TMJ) were significantly higher than in
      the control group.

PMID- 29217972
TI  - Clinical aspects and antenatal diagnosis of invasive placenta: a review of ten
      years' experience of a multi-profile hospital in Lithuania.
AB  - Background: Invasive placenta is a rare obstetrical pathology that is life
      threatening to mother and child. It is important to diagnose this pathology as
      early as possible and to plan further optimal care of patients in order to
      minimize life-threatening complications. The aim of this study was to analyze the
      frequency of cases of invasive placenta, the peculiarities of their clinical
      manifestation in women who gave birth from 2006 to 2015, to evaluate diagnostic
      and treatment options of this pathology, and to review their changes when the
      level of services provided by the institution changes. Materials and methods: A
      retrospective study was performed of the ten-year period of 2006 to 2015. The
      study consisted of examining the data of medical records of a group of 14 women.
      Results: The incidence of invasive placenta at the secondary level hospital was
      1/2170 births, 1:934 births at the tertiary level. There were only three patients
      (21.4%) diagnosed with invasive placenta during pregnancy at Vilnius University
      Hospital Santaros Klinikos Obstetrics and Gynaecology Centre. Before the surgery,
      pre-occlusive balloons were ushered into the internal iliac artery and inflated
      to reduce bleeding after the newborn delivery. The amount of blood loss in the
      whole group ranged from 1000 to 6500 ml (avg. 3130.7 ml). Radical treatment was
      given to eleven patients. Conclusion: Invasive placenta is a life-threatening
      condition. Tertiary-level hospitals have a greater capacity for antenatal
      diagnostics. Timely diagnosis of placental invasion and evaluation of the level
      of the myometrium damage before delivery is instrumental in planning patient care
      and preparing for delivery and operation.

PMID- 29217973
TI  - Hybrid transanal and total mesorectal excision after transanal endoscopic
      microsurgery for unfavourable early rectal cancer: a report of two cases.
AB  - Completion total mesorectal excision (TME) is a rare but complex procedure after
      transanal endoscopic microsurgery for early rectal cancer with unfavourable final
      histology. Two cases are reported when completion TME was performed after upfront
      transanal partial mesorectal dissection. Intact non-perforated TME specimens with
      negative and adequate distal and circumferential margins were created. The
      quality of both total mesorectal excisions was complete and distal margins were
      sufficient. We believe that our technique might be a way of approaching
      completion TME after TEM, especially in cases of low rectal cancer.

PMID- 29217974
TI  - Ketogenic Diets for Adults With Highly Refractory Epilepsy.
AB  - The current review highlights the evidence supporting the use of ketogenic diets
      in the management of drug-resistant epilepsy and status epilepticus in adults.
      Ketogenic diet variants are compared and advantages and potential side effects of
      diet therapy are discussed.

PMID- 29217975
TI  - Psychosurgery, Epilepsy Surgery, or Surgical Psychiatry: The Tangled Web of
      Epilepsy and Psychiatry as Revealed by Surgical Outcomes.

PMID- 29217976
TI  - Worrying More About Anxiety in Patients With Epilepsy.

PMID- 29217977
TI  - Combined Treatment of 'Vigabatrin and Corticoids' for Infantile Spasms: A
      Superiority Complex or Truly Superior to Corticoids Monotherapy?

PMID- 29217978
TI  - Quantitative Measurement of Longitudinal Relaxation Time (qT1) Mapping in TLE: A
      Marker for Intracortical Microstructure?

PMID- 29217979
TI  - Localizing the Ictal Onset: Visualizing the Epileptogenic Target.

PMID- 29217980
TI  - Searching for Autoimmune Epilepsy: Why, Where, and When?

PMID- 29217981
TI  - Mutating Our Understanding of Brain Tumors and Seizures: Entrez IDH.

PMID- 29217982
TI  - Expeditions in Epidemiologic Studies of New Onset Epilepsy in Older Adults: Stake
      Your Claims.

PMID- 29217983
TI  - Developmental Inflammation Takes a Toll: Early Immune Responses Increase Seizure
      Susceptibility via Astrocytic TLR4 Signaling.

PMID- 29217984
TI  - Assessing Levels of Awareness During Seizures in Animal Models.

PMID- 29217985
TI  - A Look Behind the Curtain: Epilepsy Microarray Consortium.

PMID- 29217986
TI  - Making Connections With GABA.

PMID- 29217987
TI  - Sprouted Mossy Fiber Connections of Adult-Born Granule Cells: Detonate or Fizzle?

PMID- 29217988
TI  - GRIN and Bear the Diverse Functional Effects of Rare NMDA Receptor Variants.

PMID- 29217989
TI  - Bayesian inference of metal oxide ultrathin film structure based on crystal
      truncation rod measurements.
AB  - Monte Carlo (MC)-based refinement software to analyze the atomic arrangements of
      perovskite oxide ultrathin films from the crystal truncation rod intensity is
      developed on the basis of Bayesian inference. The advantages of the MC approach
      are (i) it is applicable to multi-domain structures, (ii) it provides the
      posterior probability of structures through Bayes' theorem, which allows one to
      evaluate the uncertainty of estimated structural parameters, and (iii) one can
      involve any information provided by other experiments and theories. The simulated
      annealing procedure efficiently searches for the optimum model owing to its
      stochastic updates, regardless of the initial values, without being trapped by
      local optima. The performance of the software is examined with a five-unit-cell
      thick LaAlO3 film fabricated on top of SrTiO3. The software successfully found
      the global optima from an initial model prepared by a small grid search
      calculation. The standard deviations of the atomic positions derived from a
      dataset taken at a second-generation synchrotron are +/-0.02 A for metal sites
      and +/-0.03 A for oxygen sites.

PMID- 29217990
TI  - The electrostatic potential of dynamic charge densities.
AB  - A procedure to derive the electrostatic potential (ESP) for dynamic charge
      densities obtained from structure models or maximum-entropy densities is
      introduced. The ESP essentially is obtained by inverse Fourier transform of the
      dynamic structure factors of the total charge density corresponding to the
      independent atom model, the multipole model or maximum-entropy densities,
      employing dedicated software that will be part of the BayMEM software package.
      Our approach is also discussed with respect to the Ewald summation method. It is
      argued that a meaningful ESP can only be obtained if identical thermal smearing
      is applied to the nuclear (positive) and electronic (negative) parts of the
      dynamic charge densities. The method is applied to structure models of dl-serine
      at three different temperatures of 20, 100 and 298 K. The ESP at locations near
      the atomic nuclei exhibits a drastic reduction with increasing temperature, the
      largest difference between the ESP from the static charge density and the ESP of
      the dynamic charge density being at T = 20 K. These features demonstrate that
      zero-point vibrations are sufficient for changing the spiky nature of the ESP at
      the nuclei into finite values. On 0.5 e A-3 isosurfaces of the electron densities
      (taken as the molecular surface relevant to intermolecular interactions), the
      dynamic ESP is surprisingly similar at all temperatures, while the static ESP of
      a single molecule has a slightly larger range and is shifted towards positive
      potential values.

PMID- 29217991
TI  - Variant selection in surface martensite.
AB  - A significant variant selection is reported in isothermal martensite formed on
      the surface of an Fe-30% Ni sample. The selection phenomenon is modelled using
      different descriptions of the martensitic phase transformation. In particular,
      matrices based on the phenomenological theory of martensite crystallography, the
      Jaswon and Wheeler distortion, and the continuous face centred cubic-body centred
      cubic distortion are compared. All descriptions allow good predictions of the
      variant selection. However, the Jaswon and Wheeler distortion and the continuous
      distortion better account for other features of the surface martensite, such as
      the {225}gamma habit plane and the accommodation mechanism by twin-related
      variant pairing.

PMID- 29217992
TI  - The modular small-angle X-ray scattering data correction sequence.
AB  - Data correction is probably the least favourite activity amongst users
      experimenting with small-angle X-ray scattering: if it is not done sufficiently
      well, this may become evident only during the data analysis stage, necessitating
      the repetition of the data corrections from scratch. A recommended comprehensive
      sequence of elementary data correction steps is presented here to alleviate the
      difficulties associated with data correction, both in the laboratory and at the
      synchrotron. When applied in the proposed order to the raw signals, the resulting
      absolute scattering cross section will provide a high degree of accuracy for a
      very wide range of samples, with its values accompanied by uncertainty estimates.
      The method can be applied without modification to any pinhole-collimated
      instruments with photon-counting direct-detection area detectors.

PMID- 29217993
TI  - Hierarchical clustering for multiple-crystal macromolecular crystallography
      experiments: the ccCluster program.
AB  - This article describes ccCluster, a software providing an intuitive graphical
      user interface (GUI) and multiple functions to perform hierarchical cluster
      analysis on multiple crystallographic datasets. The program makes it easier for
      users to choose, in the case of multi-crystal data collection, those datasets
      that will be merged together to give good final statistics. It provides a simple
      GUI to analyse the dendrogram and various options for automated clustering and
      data merging.

PMID- 29217994
TI  - Local Fields in Human Subthalamic Nucleus Track the Lead-up to Impulsive Choices.
AB  - The ability to adaptively minimize not only motor but cognitive symptoms of
      neurological diseases, such as Parkinson's Disease (PD) and obsessive-compulsive
      disorder (OCD), is a primary goal of next-generation deep brain stimulation (DBS)
      devices. On the basis of studies demonstrating a link between beta-band
      synchronization and severity of motor symptoms in PD, the minimization of beta
      band activity has been proposed as a potential training target for closed-loop
      DBS. At present, no comparable signal is known for the impulsive side effects of
      PD, though multiple studies have implicated theta band activity within the
      subthalamic nucleus (STN), the site of DBS treatment, in processes of conflict
      monitoring and countermanding. Here, we address this challenge by recording from
      multiple independent channels within the STN in a self-paced decision task to
      test whether these signals carry information sufficient to predict stopping
      behavior on a trial-by-trial basis. As in previous studies, we found that local
      field potentials (LFPs) exhibited modulations preceding self-initiated movements,
      with power ramping across multiple frequencies during the deliberation period. In
      addition, signals showed phasic changes in power around the time of decision.
      However, a prospective model that attempted to use these signals to predict
      decision times showed effects of risk level did not improve with the addition of
      LFPs as regressors. These findings suggest information tracking the lead-up to
      impulsive choices is distributed across multiple frequency scales in STN, though
      current techniques may not possess sufficient signal-to-noise ratios to predict
      and thus curb-impulsive behavior on a moment-to-moment basis.

PMID- 29217995
TI  - The Alteration of Irisin-Brain-Derived Neurotrophic Factor Axis Parallels
      Severity of Distress Disorder in Bronchial Asthma Patients.
AB  - Distress disorder (a collective term for generalized anxiety disorder and major
      depressive disorder) is a well-known co-morbidity of bronchial asthma. The irisin
      brain-derived neurotrophic factor (BDNF) axis is a pathway that influences
      several neurobehavioral mechanisms involved in the pathogenesis of distress
      disorder. Thus, the aim of the present study was to quantify the serum irisin and
      BDNF concentrations in order to investigate the possible link between the
      irisin/BDNF axis and distress disorder in an asthma patient cohort. Data of 167
      therapy-controlled asthma patients were analyzed. Demographic, anthropometric,
      and anamnestic data were collected, routine laboratory parameters supplemented
      with serum irisin and BDNF levels were determined, pulmonary function test was
      performed using whole-body plethysmography, and quality of life was quantified by
      means of the St. George's Respiratory Questionnaire (SGRQ). Correlation analysis
      as well as simple and multiple linear regression were used to assess the
      relationship between the irisin level and the Impacts score of SGRQ, which latter
      is indicative of the presence and severity of distress disorder. We have found a
      significant, positive linear relationship between the Impacts score and the
      reciprocal of irisin level. This association was stronger in patients whose BDNF
      level was higher, and it was weaker (and statistically non-significant) in
      patients whose BDNF level was lower. Our results indicate that higher serum
      irisin level together with higher serum BDNF level are associated with milder (or
      no) distress disorder. This finding suggests that alteration of the irisin/BDNF
      axis influences the presence and severity of distress disorder in asthma
      patients.

PMID- 29217996
TI  - Switching between Multiple Codes of SNARC-Like Associations: Two Conceptual
      Replication Attempts with Anodal tDCS in Sham-Controlled Cross-Over Design.
AB  - In societies with left-to-right reading direction, left-side vs. right-side
      behavioral decisions are faster for relatively small vs. large number magnitudes,
      and vice versa, a phenomenon termed Spatial-Numerical Associations of Response
      Codes (SNARC) effect. But also for non-numerical sequential items, SNARC-like
      effects were observed, suggesting a common neurocognitive mechanism based on the
      ordinal structures of both numbers and sequences. Modulation of prefrontal
      networks that are involved in providing spatial associations during cognitive
      behavior can contribute to elaborate their neuropsychological theoretical
      foundations. With transcranial direct current stimulation (tDCS) directed to the
      left prefrontal cortex, we recently showed that (i) cathodal tDCS can block the
      emergence of spatial-numerical associations and that (ii) anodal tDCS can reverse
      spatial associations of sequential order, most likely based on markedness
      correspondence. Two conceptual replication attempts of the latter reversal of
      space-order associations are presented in the current sham-controlled experiment,
      using either weekdays (Monday-Friday) or month names (January-December) as
      stimuli in the temporal order classification task. In addition, to control for
      possible influences of notation, number stimuli were presented as written German
      names (One-Five). We report on a successful modulation of spatial-numerical
      associations of response codes (SNARC) effects with month stimuli induced by
      anodal tDCS, but failed to observe the same reversal of SNARC effects for weekday
      stimuli. The former stimulation effect was orthogonal to the small anodal tDCS
      effect on written number words, which replicates the dissociation of SNARC
      effects for numbers vs. non-numerical sequences. Moreover, this result reinforces
      the hypothesis that the ordinal item and task structure was the source of
      dissociation (as opposed to verbal presentation). We suggest that the diverging
      results can be explained by the markedness correspondence account of spatial
      associations in a multiple coding framework. Left-hemispheric prefrontal
      excitation from anodal tDCS renders verbal markedness relatively more dominant,
      but this effect is not absolute. We discuss task contagion, study design, and
      individual differences in performance measures or tDCS response as possible
      contributors to systematic variation of the weights of multiple coding parameters
      for spatial-numerical associations.

PMID- 29217997
TI  - Neurochemical and Behavior Deficits in Rats with Iron and Rotenone Co-treatment:
      Role of Redox Imbalance and Neuroprotection by Biochanin A.
AB  - Increasing evidences show that the etiology of Parkinson's disease (PD) is
      multifactorial. Studying the combined effect of several factors is becoming a hot
      topic in PD research. On one hand, iron is one of the essential trace metals for
      human body; on the other hand, iron may be involved in the etiopathogenesis of
      PD. In our present study, the rats with increased neonatal iron (120 MUg/g
      bodyweight) supplementation were treated with rotenone (0.5 mg/kg) when they were
      aged to 14 weeks. We observed that iron and rotenone co-treatment induced
      significant behavior deficits (time-dependent) and striatal dopamine depletion in
      the male and female rats, while they did not do so when they were used alone. No
      significant change in striatal 5-hydroxytryptamine content was observed in the
      male and female rats with iron and rotenone co-treatment. Also, iron and rotenone
      co-treatment significantly decreased substantia nigra TH expression in the male
      rats. Furthermore, co-treatment with iron and rotenone significantly induced
      malondialdehyde increase and glutathione decrease in the substantia nigra of male
      and female rats. There was no significant change in cerebellar malondialdehyde
      and glutathione content of the rats co-treated with iron and rotenone.
      Interestingly, biochanin A significantly attenuated striatal dopamine depletion
      and improved behavior deficits (dose-dependently) in the male and female rats
      with iron and rotenone co-treatment. Biochanin A treatment also significantly
      alleviated substantia nigra TH expression reduction in the male rats co-treated
      with iron and rotenone. Finally, biochanin A significantly decreased
      malondialdehyde content and increased glutathione content in the substantia nigra
      of male and female rats with iron and rotenone co-treatment. Our results indicate
      that iron and rotenone co-treatment may result in aggravated neurochemical and
      behavior deficits through inducing redox imbalance and increased neonatal iron
      supplementation may participate in the etiopathogenesis of PD. Moreover,
      biochanin A may exert dopaminergic neuroprotection by maintaining redox balance.

PMID- 29217998
TI  - Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non
      pharmacological Approaches.
AB  - Parkinson's disease (PD) is one of the most prevalent neurodegenerative disease
      displaying negative impacts on both the health and social ability of patients and
      considerable economical costs. The classical anti-parkinsonian drugs based in
      dopaminergic replacement are the standard treatment, but several motor side
      effects emerge during long-term use. This mini-review presents the rationale to
      several efforts from pre-clinical and clinical studies using adenosine receptor
      antagonists as a non-dopaminergic therapy. As several studies have indicated that
      the monotherapy with adenosine receptor antagonists reaches limited efficacy, the
      usage as a co-adjuvant appeared to be a promising strategy. The formulation of
      multi-targeted drugs, using adenosine receptor antagonists and other
      neurotransmitter systems than the dopaminergic one as targets, have been
      receiving attention since Parkinson's disease presents a complex biological
      impact. While pharmacological approaches to cure or ameliorate the conditions of
      PD are the leading strategy in this area, emerging positive aspects have arisen
      from non-pharmacological approaches and adenosine function inhibition appears to
      improve both strategies.

PMID- 29217999
TI  - Prospects for Modeling Abnormal Neuronal Function in Schizophrenia Using Human
      Induced Pluripotent Stem Cells.
AB  - Excitatory dopaminergic neurons, inhibitory GABAergic neurons, microglia, and
      oligodendrocytes have all been implicated in schizophrenia (SZ) network
      pathology. Still, SZ has been a difficult disorder to study, not only because of
      the limitations of animal models in capturing the complexity of the human mind,
      but also because it is greatly polygenic, with high rates of variability across
      the population. The advent of patient-derived pluripotent stem cells and induced
      neural and glial cultures has brought hope for modeling the molecular dysfunction
      underlying SZ pathology in a patient-specific manner. Here I review the successes
      of the patient-specific induced cultures in generating different cell types for
      the study of SZ, with special emphasis on the utility of co-culture techniques,
      both two- and three-dimensional, for modeling network dysfunction in disease.

PMID- 29218000
TI  - Synapse-Specific Regulation Revealed at Single Synapses Is Concealed When
      Recording Multiple Synapses.
AB  - Synaptic transmission and its activity-dependent modulation, known as synaptic
      plasticity, are fundamental processes in nervous system function. Neurons may
      receive thousands of synaptic contacts, but synaptic regulation may occur only at
      individual or discrete subsets of synapses, which may have important consequences
      on the spatial extension of the modulation of synaptic information. Moreover,
      while several electrophysiological methods are used to assess synaptic
      transmission at different levels of observation, i.e., through local field
      potential and individual whole-cell recordings, their experimental limitations to
      detect synapse-specific modulation is poorly defined. We have investigated how
      well-known synapse-specific short-term plasticity, where some synapses are
      regulated and others left unregulated, mediated by astrocytes and endocannabinoid
      (eCB) signaling can be assessed at different observational levels. Using
      hippocampal slices, we have combined local field potential and whole-cell
      recordings of CA3-CA1 synaptic activity evoked by Schaffer collateral stimulation
      of either multiple or single synapses through bulk or minimal stimulation,
      respectively, to test the ability to detect short-term synaptic changes induced
      by eCB signaling. We also developed a mathematical model assuming a bimodal
      distribution of regulated and unregulated synapses based on realistic
      experimental data to simulate physiological results and to predict the
      experimental requirements of the different recording methods to detect discrete
      changes in subsets of synapses. We show that eCB-induced depolarization-induced
      suppression of excitation (DSE) and astrocyte-mediated synaptic potentiation can
      be observed when monitoring single or few synapses, but are statistically
      concealed when recording the activity of a large number of synapses. These
      results indicate that the electrophysiological methodology is critical to
      properly assess synaptic changes occurring in subsets of synapses, and they
      suggest that relevant synapse-specific regulatory phenomena may be experimentally
      undetected but may have important implications in the spatial extension of
      synaptic plasticity phenomena.

PMID- 29218001
TI  - Upregulation of Cdh1 Attenuates Isoflurane-Induced Neuronal Apoptosis and Long
      Term Cognitive Impairments in Developing Rats.
AB  - Neonatal exposure to isoflurane can result in neuroapoptosis and persistent
      cognitive impairments. However, the underlying mechanisms remain elusive.
      Anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 are E3
      ubiquitin ligases that play important roles in the central nervous system,
      including in the regulation of neuronal survival, synaptic development, and
      mammalian learning and memory. However, whether APC/C-Cdh1 is involved in
      isoflurane-induced neurotoxicity in developing rats remains unclear. In this
      study, postnatal day-7 (P7) rat pups and primary hippocampal neurons were exposed
      to 2% isoflurane for 6 h. Terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) staining was used to detect neuronal apoptosis, and the
      expression of proteins involved in apoptosis (cleaved caspase-3, Bax and Bcl-2)
      was assessed by western blot. The level of Cdh1 in the hippocampus was
      downregulated during isoflurane-induced neuroapoptosis. Cdh1-encoding lentivirus
      was transfected before isoflurane-treatment to increase the level of Cdh1. Our
      results showed that Cdh1 overexpression by a recombinant Cdh1-encoding lentivirus
      reduced isoflurane-induced neuronal apoptosis. Moreover, bilateral intra
      hippocampal injection with Cdh1-encoding lentivirus attenuated long-term
      cognitive deficits after exposure to isoflurane in developing rats. Our study
      indicates that Cdh1 is an important target to prevent isoflurane-induced
      developmental neurotoxicity.

PMID- 29218002
TI  - Xenopus laevis as a Model Organism for the Study of Spinal Cord Formation,
      Development, Function and Regeneration.
AB  - The spinal cord is the first central nervous system structure to develop during
      vertebrate embryogenesis, underscoring its importance to the organism. Because of
      its early formation, accessibility to the developing spinal cord in amniotes is
      challenging, often invasive and the experimental approaches amenable to model
      systems like mammals are limited. In contrast, amphibians, in general and the
      African-clawed frog Xenopus laevis, in particular, offer model systems in which
      the formation of the spinal cord, the differentiation of spinal neurons and glia
      and the establishment of spinal neuron and neuromuscular synapses can be easily
      investigated with minimal perturbations to the whole organism. The significant
      advances on gene editing and microscopy along with the recent completion of the
      Xenopus laevis genome sequencing have reinvigorated the use of this classic model
      species to elucidate the mechanisms of spinal cord formation, development,
      function and regeneration.

PMID- 29218003
TI  - Eye-Drops for Activation of DREADDs.
AB  - Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are an
      important tool for modulating and understanding neural circuits. Depending on the
      DREADD system used, DREADD-targeted neurons can be activated or repressed in vivo
      following a dose of the DREADD agonist clozapine-N-oxide (CNO). Because DREADD
      experiments often involve behavioral assays, the method of CNO delivery is
      important. Currently, the most common delivery method is intraperitoneal (IP)
      injection. IP injection is both a fast and reliable technique, but it is painful
      and stressful particularly when many injections are required. We sought an
      alternative CNO delivery paradigm, which would retain the speed and reliability
      of IP injections without being as invasive. Here, we show that CNO can be
      effectively delivered topically via eye-drops. Eye-drops robustly activated
      DREADD-expressing neurons in the brain and peripheral tissues and does so at the
      same dosages as IP injection. Eye-drops provide an easier, less invasive and less
      stressful method for activating DREADDs in vivo.

PMID- 29218004
TI  - Decoding of Self-paced Lower-Limb Movement Intention: A Case Study on the
      Influence Factors.
AB  - Brain-machine interfaces (BMIs) have been applied as new rehabilitation tools for
      motor disabled individuals. Active involvement of cerebral activity has been
      shown to enhance neuroplasticity and thus to restore mobility. Various studies
      have focused on the detection of upper-limb movement intention, while the fewer
      study has investigated the lower-limb movement intention decoding. This study
      presents a BMI to decode the self-paced lower-limb movement intention, with 10
      healthy subjects participating in the experiment. We varied four influence
      factors including the movement type (dorsiflexion or plantar flexion), the limb
      side (left or right leg), the processing method (time-series analysis based on
      MRCP, i.e., movement-related cortical potential or frequency-domain estimation
      based on SMR, i.e., sensory motor rhythm) and the frequency band (e.g., delta,
      theta, mu, beta and MRCP band at [0.1 1] Hz), to estimate both single-trial and
      sample-based performance. Feature analysis was then conducted to show the
      discriminant power (DP) and brain modulations. The average detection latency was 
      0.334 +/- 0.216 s in single-trial basis across all conditions. An average area
      under the curve (AUC) of 91.0 +/- 3.5% and 68.2 +/- 4.6% was obtained for the
      MRCP-based and SMR-based method in the classification, respectively. The best
      performance was yielded from plantar flexion with left leg using time-series
      analysis on the MRCP band. The feature analysis indicated a cross-subject
      consistency of DP with the MRCP-based method and subject-specific variance of DP
      with the SMR-based method. The results presented here might be further exploited
      in a rehabilitation scenario. The comprehensive factor analysis might be used to
      shed light on the design of an effective brain switch to trigger external robotic
      devices.

PMID- 29218005
TI  - Distributed Neural Activity Patterns during Human-to-Human Competition.
AB  - Interpersonal interaction is the essence of human social behavior. However,
      conventional neuroimaging techniques have tended to focus on social cognition in
      single individuals rather than on dyads or groups. As a result, relatively little
      is understood about the neural events that underlie face-to-face interaction. We
      resolved some of the technical obstacles inherent in studying interaction using a
      novel imaging modality and aimed to identify neural mechanisms engaged both
      within and across brains in an ecologically valid instance of interpersonal
      competition. Functional near-infrared spectroscopy was utilized to simultaneously
      measure hemodynamic signals representing neural activity in pairs of subjects
      playing poker against each other (human-human condition) or against computer
      opponents (human-computer condition). Previous fMRI findings concerning single
      subjects confirm that neural areas recruited during social cognition paradigms
      are individually sensitive to human-human and human-computer conditions. However,
      it is not known whether face-to-face interactions between opponents can extend
      these findings. We hypothesize distributed effects due to live processing and
      specific variations in across-brain coherence not observable in single-subject
      paradigms. Angular gyrus (AG), a component of the temporal-parietal junction
      (TPJ) previously found to be sensitive to socially relevant cues, was selected as
      a seed to measure within-brain functional connectivity. Increased connectivity
      was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as
      well as a complex including the left subcentral area (SCA) and somatosensory
      cortex (SS) during interaction with a human opponent. These distributed findings
      were supported by contrast measures that indicated increased activity at the left
      dlPFC and frontopolar area that partially overlapped with the region showing
      increased functional connectivity with AG. Across-brain analyses of neural
      coherence between the players revealed synchrony between dlPFC and supramarginal
      gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus
      (FG) and SMG. These findings present the first evidence of a frontal-parietal
      neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active
      during human-to-human social cognition both within brains (functional
      connectivity) and across brains (across-brain coherence), supporting a model of
      functional integration of socially and strategically relevant information during
      live face-to-face competitive behaviors.

PMID- 29218006
TI  - Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the
      Aging Sprague-Dawley Rat.
AB  - Fragile X mental retardation protein (FMRP) encoded by Fragile X mental
      retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation,
      transport and stability with multiple targets responsible for proper synaptic
      function. Epigenetic silencing of FMR1 gene expression leads to the development
      of Fragile X syndrome (FXS) that is characterized by intellectual disability and
      other behavioral problems including autism. In the rat FXS model, the lack of
      FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal
      changes of FMRP in aging rats are not fully elucidated. The current study
      addresses the changes in FMRP levels in dentate gyrus (DG) from young (17 weeks)
      and aging (22 months) Sprague - Dawley rats. The aging animal group showed
      significant decline in spatial reference memory. Protein samples from five rats
      per each group were analyzed by quantitative proteomic analysis resulting in 153
      significantly changed proteins. FMRP showed significant reduction in aging
      animals which was confirmed by immunoblotting and immunofluorescence microscopy.
      Furthermore, bioinformatic analysis of the differential protein dataset revealed
      several functionally related protein groups with individual interactions with
      FMRP. These include high representation of the RNA translation and processing
      machinery connected to FMRP and other RNA-binding regulators including CAPRIN1,
      the members of Pumilio (PUM) and CUG-BP, Elav-like (CELF) family, and YTH N(6)
      methyladenosine RNA-binding proteins (YTHDF). The results of the current study
      point to the important role of FMRP and regulation of RNA processing in the rat
      DG and memory decline during the aging process.

PMID- 29218007
TI  - Alteration of Venous Drainage Route in Idiopathic Normal Pressure Hydrocephalus
      and Normal Aging.
AB  - Idiopathic normal pressure hydrocephalus (iNPH) is a highly prevalent condition
      in the elderly population; however, the underlying pathophysiology in relation to
      the aging process remains unclear. To investigate the effect of removal of
      cerebrospinal fluid by lumbar "tap test" on the cerebral circulation in patients
      with iNPH, 14 patients with "probable" iNPH were studied using a novel blood
      tracking technique based on blood oxygenation level-dependent (BOLD) magnetic
      resonance signal intensity. By tracking the propagation of the low-frequency
      component of the BOLD signal, extended venous drainage times were observed in the
      periventricular region of the patients, which was reversed by tap test.
      Interestingly, the venous drainage time in the periventricular region exhibited
      an age-related prolongation in the healthy control group. Additional regression
      analyses involving 81 control subjects revealed a dissociation of deep and
      superficial venous systems with increasing age, presumably reflecting focal
      inefficiency in the deep system. Our results not only provide insights into the
      etiology of iNPH, but also point to a potential non-invasive biomarker for
      screening iNPH.

PMID- 29218008
TI  - Improving the Adherence to Antiretroviral Therapy, a Difficult but Essential Task
      for a Successful HIV Treatment-Clinical Points of View and Practical
      Considerations.
AB  - HIV infection is responsible for one the most devastating human pandemics. The
      advent of antiretroviral therapy has changed the course of the pandemic and saved
      millions of lives. Complex therapeutic regimens have been introduced since 1996
      and have contributed to the transformation of HIV infection into a treatable
      chronic diseases. New types of potent antiretrovirals and their combinations,
      including "once daily" treatment, have simplified the regimens and diminished
      side effects. Nevertheless the adherence to antiretroviral therapy remains
      unsatisfactory and varies between 27 and 80% across different population in
      various studies, compared with the required level of 95%. The lack of adherence
      to antiretroviral therapy is a multi-factorial and dynamic process which raises
      considerable difficulties for long-term follow-up. Current solutions to this
      problem are complex. These should be applied by a multidisciplinary team and
      should take into account key features related to both the individual and social
      factors as well as to the population to whom it belongs (children, teenagers,
      elderly, marginalized population like drug users, incarcerated patients, sex
      workers, etc.). Importantly, adherence should continue to be monitored even in
      patients known to be compliant. In case of subsequent failure the team should
      identify the reasons for non-adherence and apply the appropriate methods. Where
      usual methods have no chance of success, a coordinated package of services also
      known as "harm reduction" can be offered in order to reduce the risks of
      transmission. The current article analyses the concept of adherence to
      antiretroviral therapy, the shortcomings of this medication and the methods that
      can be applied in practice to increase adherence. Emphasis is placed on the
      analysis of groups at high risk for HIV infection that currently represent the
      spearhead with which the HIV pandemic is spreading.

PMID- 29218011
TI  - Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol.
AB  - Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the
      preferred form. It is well known that despite its efficacy, coumarins show a high
      variability for dose requirements. We investigated the pharmacogenetic variation
      of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We
      report relevant population differentiation for variants on CYP2C8, CYP2C19,
      CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of
      novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics
      genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9)
      including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known
      variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we
      identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1),
      and CYP2D8P (1) explaining 40-55% of dose variability. A collection of
      pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also
      presented. Our results offer an initial insight into the use of a targeted NGS
      approach in the pharmacogenomics of coumarins in Mexican Mestizos.

PMID- 29218010
TI  - Calenduloside E Analogues Protecting H9c2 Cardiomyocytes Against H2O2-Induced
      Apoptosis: Design, Synthesis and Biological Evaluation.
AB  - Modulation of apoptosis is therapeutically effective in cardiomyocytes damage.
      Calenduloside E (CE), a naturally occurring triterpenoid saponin, is a potent
      anti-apoptotic agent. However, little is known about its synthetic analogues on
      the protective effects in apoptosis of cardiomyocytes. The present research was
      performed to investigate the potential protective effect of CE analogues against
      H2O2-induced apoptosis in H9c2 cardiomyocytes and the underlying mechanisms.
      Sixteen novel CE anologues have been designed, synthesized and biological
      evaluation. Among the 16 CE anologues, as well as the positive control CE tested,
      compound 5d was the most effective in improving cardiomyocytes viability.
      Pretreatment with anologue 5d inhibited ROS generation, maintained the
      mitochondrial membrane potential and reduced apoptotic cardiomyocytes. Moreover,
      exposure to H2O2 significantly increased the levels of Bax, cleaved caspase-3,
      and cleaved PARP, and decreased the level of Bcl-2, resulting in cell apoptosis.
      Pretreatment with anologue 5d (0.02-0.5 MUg/mL) dose-dependently upregulated
      antiapoptotic proteins and downregulated proapoptotic proteins mentioned above
      during H2O2-induced apoptosis. These results suggested that CE analogues provide
      protection to H9c2 cardiomyocytes against H2O2-induced oxidative stress and
      apoptosis, most likely via anti-apoptotic mechanism, and provided the basis for
      the further optimization of the CE analogues.

PMID- 29218012
TI  - Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of
      Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer.
AB  - Objective: To explore whether Rhaponticum uniflorum (R. uniflorum) had anti-tumor
      effects in oral cancer and investigate the molecular mechanisms involved in these
      anti-tumor effects. Methods: Chemical compositions of R. uniflorum ethyl acetate
      (RUEA) extracts were detected by ultra-performance liquid chromatography-Q/time
      of-flight mass spectrometry (UPLC-Q/TOF-MS), followed by pharmacology-based
      network prediction analysis. The effects of RUEA extracts on proliferation,
      apoptosis, migration, and invasion ability of human oral squamous cell carcinoma
      (OSCC) cell line SCC15 were evaluated by CCK8 assay, Annexin V- fluorescein
      isothiocyanate/propidium iodide staining, wound healing assay, and Matrigel
      invasion assay, respectively. The mRNA and protein expression of peroxiredoxin1
      (Prx1), the epithelial-to-mesenchymal transition (EMT) marker E-cadherin,
      vimentin, and Snail were determined by quantitative real-time reverse
      transcription polymerase chain reaction and western blotting. A mouse xenograft
      model of SCC15 cells was established to further evaluate the effect of RUEA
      extracts in vivo. Immunohistochemical assessment of Ki67 and terminal
      deoxynucleotidyl transferase dUTP nick end labeling staining of apoptotic cells
      were performed on the tumor tissues to assess the effects of RUEA extracts on
      proliferation and apoptosis. Results: Fourteen compounds were identified from
      RUEA extracts by UPLC-Q/TOF-MS. The pharmacology-based network prediction
      analysis showed that Prx1 could be a potential binder of RUEA extracts. In SCC15
      cells, RUEA extracts inhibited cell viability, induced apoptosis, and suppressed
      cell invasion and migration in a concentration-dependent manner. After treatment
      with RUEA extracts, the mRNA and protein expression of E-cadherin increased,
      whereas those of Prx1, vimentin, and Snail decreased. RUEA extracts also affected
      the EMT program and suppressed cell invasion and migration in Prx1 knockdown
      SCC15 cells. In an OSCC mouse xenograft model, RUEA extracts (25 and 250 mg/kg)
      significantly inhibited the growth of tumors. Compared with the control group,
      Ki67 expression was reduced and apoptosis rates were elevated in the transplanted
      tumors treated with RUEA extracts. RUEA extracts increased the expression of E
      cadherin and decreased the expression of Prx1, vimentin, and Snail in vivo.
      Conclusion: RUEA extracts inhibited tumor growth and invasion by reducing Prx1
      expression and suppressing the EMT process in OSCC. RUEA extracts may be a
      potential candidate for OSCC treatment.

PMID- 29218009
TI  - Drugs and Targets in Fibrosis.
AB  - Fibrosis contributes to the development of many diseases and many target
      molecules are involved in fibrosis. Currently, the majority of fibrosis treatment
      strategies are limited to specific diseases or organs. However, accumulating
      evidence demonstrates great similarities among fibroproliferative diseases, and
      more and more drugs are proved to be effective anti-fibrotic therapies across
      different diseases and organs. Here we comprehensively review the current
      knowledge on the pathological mechanisms of fibrosis, and divide factors
      mediating fibrosis progression into extracellular and intracellular groups.
      Furthermore, we systematically summarize both single and multiple component drugs
      that target fibrosis. Future directions of fibrosis drug discovery are also
      proposed.

PMID- 29218013
TI  - Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced
      Chronic Kidney Disease in Mice.
AB  - It is well-established that there is a crosstalk between the lung and the kidney,
      and several studies have reported association between chronic kidney disease
      (CKD) and pulmonary pathophysiological changes. Experimentally, CKD can be caused
      in mice by dietary intake of adenine. Nevertheless, the consequence of such
      intervention on the lung received only scant attention. Here, we assessed the
      pulmonary effects of adenine (0.2% w/w in feed for 4 weeks)-induced CKD in mice
      by assessing various physiological histological and biochemical endpoints.
      Adenine treatment induced a significant increase in urine output, urea and
      creatinine concentrations, and it decreased the body weight and creatinine
      clearance. It also increased proteinuria and the urinary levels of kidney injury
      molecule-1 and neutrophil gelatinase-associated lipocalin. Compared with control
      group, the histopathological evaluation of lungs from adenine-treated mice showed
      polymorphonuclear leukocytes infiltration in alveolar and bronchial walls,
      injury, and fibrosis. Moreover, adenine caused a significant increase in lung
      lipid peroxidation and reactive oxygen species and decreased the antioxidant
      catalase. Adenine also induced DNA damage assessed by COMET assay. Similarly,
      adenine caused apoptosis in the lung characterized by a significant increase of
      cleaved caspase-3. Moreover, adenine induced a significant increase in the
      expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the lung. We
      conclude that administration of adenine in mice induced CKD is accompanied by
      lung oxidative stress, DNA damage, apoptosis, and Nrf2 expression and fibrosis.

PMID- 29218014
TI  - Acute Effects of Positive Airway Pressure on Functional Mitral Regurgitation in
      Patients with Systolic Heart Failure.
AB  - Background: Acute effects of positive airway pressure (PAP) [including continuous
      PAP (CPAP) and adaptive servo-ventilation, an advanced form of bi-level PAP] on
      functional mitral regurgitation (fMR) in patients with heart failure (HF) with
      left ventricular (LV) systolic dysfunction remain unclear. Thus, whether PAP
      therapy reduces fMR in such patients with HF was investigated. Methods and
      Results: Twenty patients with HF and LV systolic dysfunction defined as LV
      ejection fraction (LVEF) <50% (14 men; mean LVEF, 35.0 +/- 11.5%) with fMR
      underwent echocardiography during 10-min CPAP (4 and 8 cm H2O) and adaptive servo
      ventilation. For fMR assessment, MR jet area fraction, defined as the ratio of MR
      jet on color Doppler to the left atrial area, was measured. The forward stroke
      volume (SV) index (fSVI) was calculated from the time-velocity integral, cross
      sectional area of the aortic annulus, and body surface area. fMR significantly
      reduced on CPAP at 8 cm H2O (0.30 +/- 0.12) and adaptive servo-ventilation (0.29
      +/- 0.12), compared with the baseline phase (0.37 +/- 0.12) and CPAP at 4 cm H2O
      (0.34 +/- 0.12) (P < 0.001). The fSVI did not change in any of the PAP sessions
      (P = 0.888). However, significant differences in fSVI responses to PAP were found
      between sexes (P for interaction, 0.006), with a significant reduction in fSVI in
      women (P = 0.041) and between patients with baseline fSVI >= and < the median
      value (27.8 ml/m2, P for interaction, 0.018), with a significant fSVI reduction
      in patients with high baseline fSVI (P = 0.028). In addition, significant
      differences were found in fSVI responses to PAP between patients with LV end
      systolic volume (LVESV) index >= and < the median value (62.0 ml/m2, P for
      interaction, 0.034), with a significant fSVI increase in patients with a high
      LVESV index (P = 0.023). Conclusion: In patients with HF, LV systolic
      dysfunction, and fMR, PAP can alleviate fMR without any overall changes in
      forward SV. However, MR alleviation due to PAP might be associated with a
      decrease in forward SV in women with high baseline SV, whereas MR alleviation due
      to PAP might be accompanied by increased forward SV in patients with a dilated
      LV.

PMID- 29218015
TI  - Trimethylamine N-oxide Supplementation Abolishes the Cardioprotective Effects of
      Voluntary Exercise in Mice Fed a Western Diet.
AB  - Excessive consumption of western diet (WD) induces obesity, resulting in cardiac
      dysfunction. Voluntary exercise ameliorates WD-induced obesity, but its effect on
      cardiac dysfunction remains unclear. Recent evidence suggests that elevated
      trimethylamine N-oxide (TMAO), a gut microbe-derived metabolite, can impair
      cardiac function in WD-induced obesity. We hypothesized that cardiac dysfunction
      in WD-induced obesity would be prevented by voluntary exercise but abolished by
      TMAO supplementation. Male CD1 mice fed a WD were assigned to sedentary, exercise
      or exercise with TMAO treatment for 8 weeks. Male CD1 mice fed a normal diet (ND)
      for 8 weeks were assigned to sedentary (control). Compared with ND-sedentary
      mice, WD-sedentary mice gained significantly more body weight and displayed
      metabolic abnormalities at the end of the experiment. Echocardiography showed
      significantly impaired cardiac systolic and diastolic function in WD-induced
      obese mice. Voluntary exercise partially attenuated weight gain and metabolic
      disorders, but completely prevented cardiac dysfunction in WD-induced obese mice.
      Molecular studies revealed that WD-sedentary mice had elevated plasma TMAO
      levels, along with increased myocardial inflammation and fibrosis, all of which
      were inhibited by voluntary exercise. Of note, concomitant administration of TMAO
      had no effects on body weight and metabolic disorders, but it abolished the
      beneficial effects of voluntary exercise on cardiac dysfunction, myocardial
      inflammation, and fibrosis in WD-induced obese mice. The results suggest that
      voluntary exercise prevents cardiac dysfunction in WD-induced obesity by
      inhibiting myocardial inflammation and fibrosis. Moreover, the cardioprotective
      effects of voluntary exercise in WD-induced obesity can be abolished by TMAO
      supplementation, which abrogates voluntary exercise-induced changes in myocardial
      inflammation and fibrosis.

PMID- 29218016
TI  - Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium
      Blockers and Acacetin.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. Developing
      effective and safe anti-AF drugs remains an unmet challenge. Simultaneous block
      of both atrial-specific ultra-rapid delayed rectifier potassium (K+) current
      (IKur) and the Na+ current (INa) has been hypothesized to be anti-AF, without
      inducing significant QT prolongation and ventricular side effects. However, the
      antiarrhythmic advantage of simultaneously blocking these two channels vs.
      individual block in the setting of AF-induced electrical remodeling remains to be
      documented. Furthermore, many IKur blockers such as acacetin and AVE0118,
      partially inhibit other K+ currents in the atria. Whether this multi-K+-block
      produces greater anti-AF effects compared with selective IKur-block has not been
      fully understood. The aim of this study was to use computer models to (i) assess
      the impact of multi-K+-block as exhibited by many IKur blokers, and (ii) evaluate
      the antiarrhythmic effect of blocking IKur and INa, either alone or in
      combination, on atrial and ventricular electrical excitation and recovery in the
      setting of AF-induced electrical-remodeling. Contemporary mathematical models of
      human atrial and ventricular cells were modified to incorporate dose-dependent
      actions of acacetin (a multichannel blocker primarily inhibiting IKur while less
      potently blocking Ito, IKr, and IKs). Rate- and atrial-selective inhibition of
      INa was also incorporated into the models. These single myocyte models were then
      incorporated into multicellular two-dimensional (2D) and three-dimensional (3D)
      anatomical models of the human atria. As expected, application of IKur blocker
      produced pronounced action potential duration (APD) prolongation in atrial
      myocytes. Furthermore, combined multiple K+-channel block that mimicked the
      effects of acacetin exhibited synergistic APD prolongations. Synergistically anti
      AF effects following inhibition of INa and combined IKur/K+-channels were also
      observed. The attainable maximal AF-selectivity of INa inhibition was greatly
      augmented by blocking IKur or multiple K+-currents in the atrial myocytes. This
      enhanced anti-arrhythmic effects of combined block of Na+- and K+-channels were
      also seen in 2D and 3D simulations; specially, there was an enhanced efficacy in
      terminating re-entrant excitation waves, exerting improved antiarrhythmic effects
      in the human atria as compared to a single-channel block. However, in the human
      ventricular myocytes and tissue, cellular repolarization and computed QT
      intervals were modestly affected in the presence of actions of acacetin and INa
      blockers (either alone or in combination). In conclusion, this study demonstrates
      synergistic antiarrhythmic benefits of combined block of IKur and INa, as well as
      those of INa and combined multi K+-current block of acacetin, without significant
      alterations of ventricular repolarization and QT intervals. This approach may be
      a valuable strategy for the treatment of AF.

PMID- 29218017
TI  - Six2 Plays an Intrinsic Role in Regulating Proliferation of Mesenchymal Cells in
      the Developing Palate.
AB  - Cleft palate is a common congenital abnormality that results from defective
      secondary palate (SP) formation. The Sine oculis-related homeobox 2 (Six2) gene
      has been linked to abnormalities of craniofacial and kidney development. Our
      current study examined, for the first time, the specific role of Six2 in
      embryonic mouse SP development. Six2 mRNA and protein expression were identified
      in the palatal shelves from embryonic days (E)12.5 to E15.5, with peak levels
      during early stages of palatal shelf outgrowth. Immunohistochemical staining
      (IHC) showed that Six2 protein is abundant throughout the mesenchyme in the oral
      half of each palatal shelf, whereas there is a pronounced decline in Six2
      expression by mesenchyme cells in the nasal half of the palatal shelf by stages
      E14.5-15.5. An opposite pattern was observed in the surface epithelium of the
      palatal shelf. Six2 expression was prominent at all stages in the epithelial cell
      layer located on the nasal side of each palatal shelf but absent from the
      epithelium located on the oral side of the palatal shelf. Six2 is a putative
      downstream target of transcription factor Hoxa2 and we previously demonstrated
      that Hoxa2 plays an intrinsic role in embryonic palate formation. We therefore
      investigated whether Six2 expression was altered in the developing SP of Hoxa2
      null mice. Reverse transcriptase PCR and Western blot analyses revealed that Six2
      mRNA and protein levels were upregulated in Hoxa2-/- palatal shelves at stages
      E12.5-14.5. Moreover, the domain of Six2 protein expression in the palatal
      mesenchyme of Hoxa2-/- embryos was expanded to include the entire nasal half of
      the palatal shelf in addition to the oral half. The palatal shelves of Hoxa2-/-
      embryos displayed a higher density of proliferating, Ki-67 positive palatal
      mesenchyme cells, as well as a higher density of Six2/Ki-67 double-positive
      cells. Furthermore, Hoxa2-/- palatal mesenchyme cells in culture displayed both
      increased proliferation and elevated Cyclin D1 expression relative to wild-type
      cultures. Conversely, siRNA-mediated Six2 knockdown restored proliferation and
      Cyclin D1 expression in Hoxa2-/- palatal mesenchyme cultures to near wild-type
      levels. Our findings demonstrate that Six2 functions downstream of Hoxa2 as a
      positive regulator of mesenchymal cell proliferation during SP development.

PMID- 29218018
TI  - Aerobic Interval Training and Cardiometabolic Health in Patients with Type 2
      Diabetes: A Meta-Analysis.
AB  - Vigorous to maximal aerobic interval training (INT) has received remarkable
      interest in improving cardiometabolic outcomes for type 2 diabetes patients
      recently, yet with inconsistent findings. This meta-analysis was aimed to
      quantify its effectiveness in type 2 diabetes. Randomized controlled trials
      (RCTs) were identified by searches of 3 databases to October 2017, which
      evaluated the effects of INT with a minimal training duration of 8 weeks vs.
      moderate-intensity continuous training (MICT) or non-exercise training (NET)
      among type 2 diabetes patients on outcomes including cardiorespiratory fitness,
      glycemic control, body composition, blood pressure, and lipid profiles. Weighted
      mean differences with 95% confidence intervals (CIs) were calculated with the
      random-effects model. Nine datasets from 7 RCTs with 189 patients were included.
      Compared with MICT, INT improved maximal oxygen consumption (VO2max) by 2.60
      ml/kg/min (95% CI: 1.32 to 3.88 ml/kg/min, P <0.001) and decreased hemoglobin A1c
      (HbA1c) by 0.26% (95% CI: -0.46% to -0.07%, P = 0.008). These outcomes for INT
      were also significant vs. energy expenditure-matched MICT, with VO2max increased
      by 2.18 ml/kg/min (P = 0.04) and HbA1c decreased by 0.28% (P = 0.01). Yet their
      magnitudes of changes were larger compared with NET, with VO2max increased by
      6.38 ml/kg/min (P <0.001) and HbA1c reduced by 0.83% (P = 0.004). Systolic blood
      pressure could be lowered by INT compared with energy expenditure-matched MICT or
      NET (both P <0.05), but other cardiometabolic markers and body composition were
      not significantly altered in general. In conclusion, despite a limited number of
      studies, INT improves cardiometabolic health especially for VO2max and HbA1c
      among patients with type 2 diabetes, and might be considered an alternative to
      MICT. Yet the optimal training protocols still require to be established.

PMID- 29218019
TI  - Dietary n-3 Polyunsaturated Fatty Acids in Late Pregnancy and Postpartum
      Depressive Symptom among Japanese Women.
AB  - Background: The use of n-3 polyunsaturated fatty acids (n-3PUFA) in preventive or
      therapeutic modalities for postpartum depression, especially long-chain types
      such as eicosapentaenoic acid (EPA) and a docosahexaenoic acid (DHA), is of
      considerable interest. High n-3PUFA consumption has been reported among pregnant
      Japanese women. Therefore, analysis of this group could provide important
      insights into the relationship between postpartum depression and dietary n-3PUFA
      consumption. To further examine the relationship between the risk of postpartum
      depression and n-3PUFA consumption, we conducted a prospective hospital-based
      birth cohort study in Japan. Design and methods: Our prospective birth cohort
      study was performed at the National Center for Child Health and Development
      (NCCHD) in suburban Tokyo, Japan. Dietary n-3PUFA intake during late pregnancy
      was assessed by a semi-quantitative food questionnaire and participants were
      categorized by quintile distributions of n-3PUFA intake. A Japanese translation
      of the Edinburgh Postnatal Depression Scale was used to screen women for
      postpartum depression at 1 month after delivery (967 women) and at 6 months after
      delivery (710 women). We performed logistic regression analysis to examine the
      relationship between the risk of postpartum depression and n-3PUFA consumption
      after adjusting for confounding factors. Results: Significant associations
      between EPA, DHA, and n-3PUFA intakes in late pregnancy and postpartum depression
      at both 1 and 6 months after delivery were not observed. Conclusion: This
      prospective study indicated that EPA, DHA, and n-3PUFA intake during late
      pregnancy was not associated with the risk of postpartum depression.

PMID- 29218020
TI  - Peripheral Immune Alterations in Major Depression: The Role of Subtypes and
      Pathogenetic Characteristics.
AB  - Depression has been associated with peripheral inflammatory processes and
      alterations in cellular immunity. Growing evidence suggests that immunological
      alterations may neither be necessary nor sufficient to induce depression in
      general, but seem to be associated with specific features. Using baseline data
      from the Outcome of Psychological Interventions in Depression trial, this
      exploratory study examines associations between depression subtypes and
      pathogenetic characteristics (i.e., melancholic vs non-melancholic depression,
      chronic vs non-chronic depression, age of onset, cognitive-affective and somatic
      symptom dimensions) with plasma levels of C-reactive protein (CRP), interleukin
      (IL)-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major
      depression (MD) and 30 age and sex-matched controls. Patients with MD exhibited
      higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and
      an increased neutrophil to lymphocyte ratio (NLR) than controls. Patient with
      later age of onset had higher levels of two inflammatory markers (CRP, NLR) and
      lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle
      factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels
      were related to more severe somatic depressive symptoms. These results confirm
      and extend previous findings suggesting that increased levels of CRP are
      associated with a later onset of depression and demonstrate that also NLR as a
      subclinical inflammatory marker is related to a later onset of depression.

PMID- 29218021
TI  - The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical,
      Metabolic, Cognitive, and Olfactory Function in Young Male Subjects.
AB  - Food intake influences human cognition, olfaction, hunger, and food craving.
      However, little research has been done in this field to elucidate the effects of
      different nutrients. Thus, the goal of our study was to investigate the effects
      of oral ingestion of different nutrient solutions on olfactory, cognitive,
      metabolic and psychophysical function. Twenty healthy men participated in our
      study employing a double-blind, cross-over, repeated measurement design.
      Participants were tested on four different study days. Each day participants
      received, in randomized order, one of three isocaloric (protein, carbohydrate or
      fat 600 kcal, 1,500 mL) solutions or a placebo. Olfactory and cognitive tests
      (monitoring only) were conducted three times, i.e., 60 min before the beginning
      of nutrient intake, following oral ingestion of the solution and 60, and 240 min
      after. Psychophysical and metabolic function tests (active grehlin, desacyl
      ghrelin, insulin, glucagon, glucose, triglyceride, urea) were performed 7 times
      on each examination day (observation period: -60 min, 0 = solution intake, +60,
      +120, +180, +240, and +300 min). Ratings of hunger and food craving significantly
      differed over the observation period with lowest ratings following application of
      the protein solution. Highest ratings of craving were found following placebo
      intake. We further observed a significant positive correlation of active grehlin
      with hunger and fat, protein and sweets craving for each nutrient solution.
      Active grehlin significantly correlated with carbohydrate craving for
      carbohydrate and fat solution and with vegetable craving for fat solution only.
      Hunger hormone levels, hunger and food craving ratings demonstrated that the
      hierarchical order that appears in satiating efficiencies of isovolumetric
      isocaloric ingested macronutrients is protein > fat > carbohydrate. Our study
      reveals that the type of nutrient exerts a significant influence on metabolic
      parameters, hunger and food craving.

PMID- 29218022
TI  - Association between Unintentional Interpersonal Postural Coordination Produced by
      Interpersonal Light Touch and the Intensity of Social Relationship.
AB  - Interpersonal postural coordination (IPC) produced by interpersonal light touch
      (ILT), whereby time-series variations in the postural sway between two people
      unintentionally resemble each other, may be a possible social interaction. From a
      sociopsychological standpoint, close mutual behavioral coordination is recognized
      as "social glue," which represents the closeness of relationships and contributes
      to the building of a good rapport. Therefore, we hypothesized that if IPC
      functions as social glue, then IPC produced by ILT also represents a social
      relationship. Participants were dyadic pairs with a preexisting social
      relationship (acquaintance, friend, or best-friend), and we assessed the
      closeness between the partners. Postural sway in two quiet standing conditions-no
      touch (NT) and ILT (a mutual light touch with <1 N) condition-was concurrently
      measured with the side-by-side standing position, and the association of IPC with
      intradyadic closeness (rapport) was analyzed using hierarchical linear modeling.
      The results showed that unintentional IPC was higher in both axes of the ILT
      condition than in NT condition. Additionally, IPC in the mediolateral axis (the
      partner side) of the ILT condition was positively correlated with intradyadic
      closeness, whereas that in the anteroposterior axis (the non-partner side) showed
      a negative association. As expected, IPC represented intradyadic closeness
      (rapport). Results indicate that, in unintentional IPC produced by ILT, the
      priority of processing sensory feedback for postural control, which is received
      from the individual and a partner, is modulated depending on the rapport in
      interactional coupled feedback loops between the two individuals (i.e., good
      rapport increases the degree of taking in feedback from a partner). Thus,
      unintentional IPC produced by ILT functions as social glue, and it provides an
      understanding of the sociopsychological aspect in the human-to-human postural
      coordination mechanism.

PMID- 29218023
TI  - On the Diversity of Linguistic Data and the Integration of the Language Sciences.
AB  - An integrated science of language is usually advocated as a step forward for
      linguistic research. In this paper, we maintain that integration of this sort is
      premature, and cannot take place before we identify a common object of study. We
      advocate instead a science of language that is inherently multi-faceted, and
      takes into account the different viewpoints as well as the different definitions
      of the object of study. We also advocate the use of different data sources,
      which, if non-contradictory, can provide more solid evidence for linguistic
      analysis. Last, we argue that generative grammar is an important tile in the
      puzzle.

PMID- 29218024
TI  - Impact of Spatial and Verbal Short-Term Memory Load on Auditory Spatial Attention
      Gradients.
AB  - Short-term memory load can impair attentional control, but prior work shows that
      the extent of the effect ranges from being very general to very specific. One
      factor for the mixed results may be reliance on point estimates of memory load
      effects on attention. Here we used auditory attention gradients as an analog
      measure to map-out the impact of short-term memory load over space. Verbal or
      spatial information was maintained during an auditory spatial attention task and
      compared to no-load. Stimuli were presented from five virtual locations in the
      frontal azimuth plane, and subjects focused on the midline. Reaction times
      progressively increased for lateral stimuli, indicating an attention gradient.
      Spatial load further slowed responses at lateral locations, particularly in the
      left hemispace, but had little effect at midline. Verbal memory load had no
      (Experiment 1), or a minimal (Experiment 2) influence on reaction times. Spatial
      and verbal load increased switch costs between memory encoding and attention
      tasks relative to the no load condition. The findings show that short-term memory
      influences the distribution of auditory attention over space; and that the
      specific pattern depends on the type of information in short-term memory.

PMID- 29218025
TI  - Stimulating the Right Temporoparietal Junction with tDCS Decreases Deception in
      Moral Hypocrisy and Unfairness.
AB  - Self-centered and other-regarding concerns play important roles in decisions of
      deception. To investigate how these two motivations affect deception in fairness
      related moral hypocrisy, we modulated the brain activity in the right
      temporoparietal junction (rTPJ), the key region for decision making involved in
      self-centered and other-regarding concerns. After receiving brain stimulation
      with transcranial direct current stimulation (tDCS), participants finished a
      modified dictator game. In the game, they played as proposers to make allocations
      between themselves and recipients and had a chance to deceive by misreporting
      their totals for allocations. Results show that deception in moral hypocrisy was
      decreased after anodal stimulation than sham and cathodal stimulation, only when
      participants know that their reported totals (appearing fair) would be revealed
      to recipients rather than being unrevealed. Anodal stimulation also increased
      offers to recipients than cathodal stimulation regardless of the revelation of
      reported totals. These findings suggest that enhancing the activity of rTPJ
      decreased deception caused by impression management rather than self-deception in
      moral hypocrisy and unfairness through facilitating other-regarding concerns and
      weakening non-material self-centered motivations. They provide causal evidence
      for the role of rTPJ in both other-regarding concerns and non-material self
      centered motivations, shedding light on the way to decrease moral hypocrisy.

PMID- 29218026
TI  - Contests versus Norms: Implications of Contest-Based and Norm-Based Intervention
      Techniques.
AB  - Interventions using either contests or norms can promote environmental behavioral
      change. Yet research on the implications of contest-based and norm-based
      interventions is lacking. Based on Goal-framing theory, we suggest that a contest
      based intervention frames a gain goal promoting intensive but instrumental
      behavioral engagement. In contrast, the norm-based intervention was expected to
      frame a normative goal activating normative obligations for targeted and non
      targeted behavior and motivation to engage in pro-environmental behaviors in the
      future. In two studies participants (n = 347) were randomly assigned to either a
      contest- or a norm-based intervention technique. Participants in the contest
      showed more intensive engagement in both studies. Participants in the norm-based
      intervention tended to report higher intentions for future energy conservation
      (Study 1) and higher personal norms for non-targeted pro-environmental behaviors
      (Study 2). These findings suggest that contest-based intervention technique
      frames a gain goal, while norm-based intervention frames a normative goal.

PMID- 29218027
TI  - Corrigendum: Assessing Metabolism and Injury in Acute Human Traumatic Brain
      Injury with Magnetic Resonance Spectroscopy: Current and Future Applications.
AB  - [This corrects the article on p. 426 in vol. 8, PMID: 28955291.].

PMID- 29218028
TI  - The Folate Cycle As a Cause of Natural Killer Cell Dysfunction and Viral Etiology
      in Type 1 Diabetes.
AB  - The folate pathway is critical to proper cellular function and metabolism. It is
      responsible for multiple functions, including energy (ATP) production,
      methylation reactions for DNA and protein synthesis and the production of
      immunomodulatory molecules, inosine and adenosine. These play an important role
      in immune signaling and cytotoxicity. Herein, we hypothesize that defects in the
      folate pathway in genetically susceptible individuals could lead to immune
      dysfunction, permissive environments for chronic cyclical latent/lytic viral
      infection, and, ultimately, the development of unchecked autoimmune responses to
      infected tissue, in this case islet beta cells. In the context of type 1 diabetes
      (T1D), there has been a recent increase in newly diagnosed cases of T1D in the
      past 20 years that has exceeded previous epidemiological predictions with yet
      unidentified factor(s). This speaks to a potential environmental trigger that
      adversely affects immune responses. Most research into the immune dysfunction of
      T1D has focused on downstream adaptive responses of T and B cells neglecting the
      role of the upstream innate players such as natural killer (NK) cells.
      Constantly, surveilling the blood and tissues for pathogens, NK cells remove
      threats through direct cytotoxic responses and recruitment of adaptive responses
      using cytokines, such as IL-1beta and IFN-gamma. One long-standing hypothesis
      suggests viral infection as a potential trigger for the autoimmune response in
      T1D. Recent data suggest multiple viruses as potential causal agents. Intertwined
      with this is an observed reduced NK cell enumeration, cytotoxicity, and cytokine
      signaling in T1D patients. Many of the viruses implicated in T1D are chronic
      latent/lysogenic infections with demonstrated capacity to reduce NK cell response
      and number through mechanisms that resemble those of pregnancy tolerance. Defects
      in the folate pathway in T1D patients could result in decreased immune response
      to viral infection or viral reactivation. Dampened NK responses to infections
      result in improper signaling, improper antigen presentation, and amplified CD8+
      lymphocyte proliferation and cytotoxicity, a hallmark of beta cell infiltrates in
      patients with T1D onset. This would suggest a critical role for NK cells in T1D
      development linked to viral infection and the importance of the folate pathway in
      maintaining proper NK response.

PMID- 29218029
TI  - Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of
      Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell
      Transplantation and Conventional Medical Therapy.
AB  - Objective: To explore the impact on microvascular complications, long-term
      preservation of residual B-cell function and glycemic control of patients with
      type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell
      transplantation (AHST) compared with conventional medical therapy (CT). Research
      design and methods: Cross-sectional data of patients treated with AHST were
      compared with patients who received conventional therapy from the Brazilian Type
      1 Diabetes Study Group, the largest multicenter observational study in type 1
      diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on
      average. An assessment comparison was made on the presence of microvascular
      complications, residual function of B cell, A1c, and insulin dose of the
      patients. Results: After a median of 8 years of diagnosis, none of the AHST
      treated patients (n = 24) developed microvascular complications, while 21.5%
      (31/144) had at least one (p < 0.005) complication in the CT group (n = 144).
      Furthermore, no case of nephropathy was reported in the AHST group, while 13.8%
      of CT group (p < 0.005) developed nephropathy during the same period. With regard
      of residual B-cell function, the percentage of individuals with predicted higher
      C-peptide levels (IDAA1C <= 9) was about 10-fold higher in the AHST group
      compared with CT (75 vs. 8.3%) (p < 0.001) group. Among AHST patients, 54.1%
      (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT (p < 0.001) group.
      Conclusion: Patients with newly diagnosed type 1 diabetes treated with AHST
      presented lower prevalence of microvascular complications, higher residual B-cell
      function, and better glycemic control compared with the CT group.

PMID- 29218030
TI  - In Situ Antibacterial Activity of Essential Oils with and without Alcohol on Oral
      Biofilm: A Randomized Clinical Trial.
AB  - Currently, there is little evidence on the in situ antibacterial activity of
      essential oils (EO) without alcohol. This study aimed to evaluate in situ the
      substantivity and antiplaque effect on the plaque-like biofilm (PL-biofilm) of
      two solutions, a traditional formulation that contains EO with alcohol (T-EO) and
      an alcohol-free formulation of EO (Af-EO). Eighteen healthy adults performed a
      single mouthwash of: T-EO, Af-EO, and sterile water (WATER) after wearing an
      individualized disk-holding splint for 2 days. The bacterial viability (BV) and
      thickness of the PL-biofilm were quantified at baseline, 30 s, and 1, 3, 5, and 7
      h post-rinsing (Test 1). Subsequently, each volunteer wore the splint for 4 days,
      applying two daily mouthwashes of: T-EO, Af-EO, and WATER. The BV, thickness, and
      covering grade (CG) of the PL-biofilm were quantified (Test 2). Samples were
      analyzed by confocal laser scanning microscopy after staining with the
      LIVE/DEAD(r) BacLightTM solution. To conduct the computations of the BV
      automatically, a Matlab toolbox called Dentius Biofilm was developed. In test 1,
      both EO antiseptics had a similar antibacterial effect, reducing BV after a
      single rinse compared to the WATER, and keeping it below baseline levels up to 7
      h post-rinse (P < 0.001). The mean thickness of the PL-biofilm after rinsing was
      not affected by any of the EO formulations and ranged from 18.58 to 20.19 MUm.
      After 4 days, the T-EO and Af-EO solutions were significantly more effective than
      the WATER, reducing the BV, thickness, and CG of the PL-biofilm (P < 0.001).
      Although, both EO antiseptics presented a similar bactericidal activity, the Af
      EO rinses led to more significant reductions in the thickness and CG of the PL
      biofilm than the T-EO rinses (thickness = 7.90 vs. 9.92 MUm, P = 0.012; CG =
      33.36 vs. 46.61%, P = 0.001). In conclusion, both essential oils antiseptics had
      very high immediate antibacterial activity and substantivity in situ on the 2-day
      PL-biofilm after a single mouthwash. In the 4-day PL-biofilm, both essential oils
      formulations demonstrated a very good antiplaque effect in situ, although the
      alcohol-free formula performed better at reducing the biofilm thickness and
      covering grade.

PMID- 29218032
TI  - Surface Proteins of Lactococcus lactis: Bacterial Resources for Muco-adhesion in
      the Gastrointestinal Tract.
AB  - Food and probiotic bacteria, in particular lactic acid bacteria, are ingested in
      large amounts by humans and are part of the transient microbiota which is
      increasingly considered to be able to impact the resident microbiota and thus
      possibly the host health. The lactic acid bacterium Lactococcus lactis is
      extensively used in starter cultures to produce dairy fermented food. Also
      because of a generally recognized as safe status, L. lactis has been considered
      as a possible vehicle to deliver in vivo therapeutic molecules with anti
      inflammatory properties in the gastrointestinal tract. One of the key factors
      that may favor health effects of beneficial bacteria to the host is their
      capacity to colonize transiently the gut, notably through close interactions with
      mucus, which covers and protects the intestinal epithelium. Several L. lactis
      strains have been shown to exhibit mucus-binding properties and bacterial surface
      proteins have been identified as key determinants of such capacity. In this
      review, we describe the different types of surface proteins found in L. lactis,
      with a special focus on mucus-binding proteins and pili. We also review the
      different approaches used to investigate the adhesion of L. lactis to mucus, and
      particularly to mucins, one of its major components, and we present how these
      approaches allowed revealing the role of surface proteins in muco-adhesion.

PMID- 29218031
TI  - CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human
      Gut Microbiome.
AB  - Background: While CRISPR-Cas systems have been identified in bacteria from a wide
      variety of ecological niches, there are no studies to describe CRISPR-Cas
      elements in Bacteroides species, the most prevalent anaerobic bacteria in the
      lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the
      total gut microbiome. Bacteroides fragilis comprises only 2% of the total
      Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors
      causing it to transition from benign resident of the gut microbiome to virulent
      pathogen are not well understood, but a combination of horizontal gene transfer
      (HGT) of virulence genes and differential transcription of endogenous genes are
      clearly involved. The CRISPR-Cas system is a multi-functional system described in
      prokaryotes that may be involved in control both of HGT and of gene regulation.
      Results: Clustered regularly interspaced short palindromic repeats (CRISPR)
      elements in all strains of B. fragilis (n = 109) with publically available
      genomes were identified. Three different CRISPR-Cas types, corresponding most
      closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains
      had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types
      in their respective genomes. The cas1 gene in the Type IIIB system encoded a
      reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We
      identified a short CRISPR (3 DR) with no associated cas genes present in most of
      the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon
      and we speculate that this element may be involved in regulation of this operon
      related to formation of persister cells during antimicrobial exposure. Also,
      blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had
      atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes.
      Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide
      range of B. fragilis strains from a variety of sources. There are four apparent
      CRISPR-Cas systems in B. fragilis-three systems have adjacent cas genes.
      Understanding CRISPR/Cas function in B. fragilis will elucidate their role in
      gene expression, DNA repair and ability to survive exposure to antibiotics. Also,
      based on their unique CRISPR-Cas arrays, their phylogenetic clustering and their
      virulence potential, we are proposing that blood isolates of B. fragilis be
      viewed a separate subgroup.

PMID- 29218033
TI  - Substrate-Limited and -Unlimited Coastal Microbial Communities Show Different
      Metabolic Responses with Regard to Temperature.
AB  - Bacteria are the principal consumers of dissolved organic carbon (DOC) in the
      ocean and predation of bacteria makes organic carbon available to higher trophic
      levels. The efficiency with which bacteria convert the consumed carbon (C) into
      biomass (i.e., carbon growth efficiency, Y) determines their ecological as well
      as biogeochemical role in marine ecosystems. Yet, it is still unclear how changes
      in temperature will affect Y and, hence, the transfer of consumed C to higher
      trophic levels. Here, we experimentally investigated the effect of temperature on
      metabolic functions of coastal microbial communities inoculated in both nutrient
      limited chemostats and nutrient-unlimited turbidostats. We inoculated chemostats
      and turbidostats with coastal microbial communities into seawater culture medium
      augmented with 20 and 100 MUmol L-1 of glucose respectively and measured CO2
      production, carbon biomass and cell abundance. Chemostats were cultured between
      14 and 26 degrees C and specific growth rates (MU) between 0.05 and 6.0 day-1,
      turbidostats were cultured between 10 and 26 degrees C with specific growth rates
      ranging from 28 to 62 day-1. In chemostats under substrate limitation, which is
      common in the ocean, the specific respiration rate (r, day-1) showed no trend
      with temperature and was roughly proportional to MU, implying that carbon growth
      efficiency (Y) displayed no tendency with temperature. The response was very
      different in turbidostats under temperature-limited, nutrient-repleted growth,
      here MU increased with temperature but r decreased resulting in an increase of Y
      with temperature (Q10: 2.6). Comparison of our results with data from the
      literature on the respiration rate and cell weight of monospecific bacteria
      indicates that in general the literature data behaved similar to chemostat data,
      showing no trend in specific respiration with temperature. We conclude that
      respiration rates of nutrient-limited bacteria measured at a certain temperature
      cannot be adjusted to different temperatures with a temperature response function
      similar to Q10 or Arrhenius. However, the cellular respiration rate and carbon
      demand rate (both: mol C cell-1 day-1) show statistically significant relations
      with cellular carbon content (mol C cell-1) in chemostats, turbidostats, and the
      literature data.

PMID- 29218035
TI  - Characterization of Two Cryptic Plasmids Isolated in Haiti from Clinical Vibrio
      cholerae Non-O1/Non-O139.
AB  - We report the complete sequence of two novel plasmids, pSDH-1 and pSDH-2,
      isolated from clinical Vibrio cholerae non-O1/non-O139 during the early phase of
      the 2010 Haitian cholera epidemic. Plasmids were revealed by employing single
      cell genomics and their genome content suggests self-mobilization and, for pSDH
      2, a toxin-antitoxin (TA) system for plasmid stabilization was identified. The
      putative origin of replication of pSDH-2 was mapped suggesting it replicates
      following the ColE1 model of plasmid replication. pSDH-1 and pSDH-2 were
      widespread among environmental V. cholerae non-O1/non-O139 with variable
      prevalence in four Haitian Departments. pSDH-2 was the most common element,
      either alone or with pSDH-1. The two plasmids detection adds to the composite
      scenario of mobile genetic elements (MGEs) observed in V. cholerae in Haiti. The
      role these small cryptic plasmids circulating in Vibrio spp. play in bacterial
      fitness or pathogenicity merits further investigation.

PMID- 29218034
TI  - Replication of Staphylococcal Resistance Plasmids.
AB  - The currently widespread and increasing prevalence of resistant bacterial
      pathogens is a significant medical problem. In clinical strains of staphylococci,
      the genetic determinants that confer resistance to antimicrobial agents are often
      located on mobile elements, such as plasmids. Many of these resistance plasmids
      are capable of horizontal transmission to other bacteria in their surroundings,
      allowing extraordinarily rapid adaptation of bacterial populations. Once the
      resistance plasmids have been spread, they are often perpetually maintained in
      the new host, even in the absence of selective pressure. Plasmid persistence is
      accomplished by plasmid-encoded genetic systems that ensure efficient replication
      and segregational stability during cell division. Staphylococcal plasmids utilize
      proteins of evolutionarily diverse families to initiate replication from the
      plasmid origin of replication. Several distinctive plasmid copy number control
      mechanisms have been studied in detail and these appear conserved within plasmid
      classes. The initiators utilize various strategies and serve a multifunctional
      role in (i) recognition and processing of the cognate replication origin to an
      initiation active form and (ii) recruitment of host-encoded replication proteins
      that facilitate replisome assembly. Understanding the detailed molecular
      mechanisms that underpin plasmid replication may lead to novel approaches that
      could be used to reverse or slow the development of resistance.

PMID- 29218037
TI  - Wuji Wan Formula Ameliorates Diarrhea and Disordered Colonic Motility in Post
      inflammation Irritable Bowel Syndrome Rats by Modulating the Gut Microbiota.
AB  - Emerging evidence suggests that gut microbiota contribute to the treatment of
      post-inflammatory irritable bowel syndrome (PI-IBS). Our previous studies have
      demonstrated that a Chinese formula, Wuji Wan, has the ability to mitigate
      abdominal pain and diarrhea in PI-IBS rats. However, little is known about the
      underlying mechanism and whether the gut microbiota mediate the effect of Wuji
      Wan on PI-IBS. Thus, the aim of this study was to determine whether Wuji Wan
      mitigated PI-IBS by modifying the gut microbiota. PI-IBS was induced in Sprague
      Dawley rats by enema using 4% acetic acid and restraint stress. Rats were fed
      water, Wuji Wan extract (630 mg/kg) or pinaverium bromide (13.5 mg/kg). Our data
      showed that Wuji Wan effectively ameliorated abdominal pain, colonic motility
      abnormality and visceral hypersensitivity. Analysis of the fecal microbiota
      showed that Wuji Wan could reverse the reduction in richness of the gut
      microbiota and significantly increase the relative abundances of Akkermansia,
      Bacteroides, and Parasutterella; however, Lactobacillus and Prevotella were
      markedly decreased in the PI-IBS rats. Moreover, Wuji Wan promoted goblet cell
      proliferation in the colonic mucosa by increasing the release of mucin, up
      regulating the distribution of tight junction proteins Occludin and ZO-1 and down
      regulating the expression of MLCK in colonic epithelial cells. These findings
      suggest that Wuji Wan may remit IBS by modulating the gut microbiota and
      stabilizing the gut mucosal barrier, indicating that the use of a classical
      formula of Traditional Chinese Medicine (TCM) that exhibits a prebiotic effect
      may be a promising strategy for PI-IBS treatment.

PMID- 29218036
TI  - The Macrophage: A Disputed Fortress in the Battle against Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis
      (TB), has plagued humans for thousands of years. TB still remains a major public
      health problem in our era, causing more than 4,400 deaths worldwide every day and
      killing more people than HIV. After inhaling Mtb-contaminated aerosols, TB primo
      infection starts in the terminal lung airways, where Mtb is taken up by alveolar
      macrophages. Although macrophages are known as professional killers for
      pathogens, Mtb has adopted remarkable strategies to circumvent host defenses,
      building suitable conditions to survive and proliferate. Within macrophages, Mtb
      initially resides inside phagosomes, where its survival mostly depends on its
      ability to take control of phagosomal processing, through inhibition of
      phagolysosome biogenesis and acidification processes, and by progressively
      getting access to the cytosol. Bacterial access to the cytosolic space is
      determinant for specific immune responses and cell death programs, both required
      for the replication and the dissemination of Mtb. Comprehension of the molecular
      events governing Mtb survival within macrophages is fundamental for the
      improvement of vaccine-based and therapeutic strategies in order to help the host
      to better defend itself in the battle against the fierce invader Mtb. In this
      mini-review, we discuss recent research exploring how Mtb conquers and transforms
      the macrophage into a strategic base for its survival and dissemination as well
      as the associated defense strategies mounted by host.

PMID- 29218038
TI  - Application of Nonphosphorylative Metabolism as an Alternative for Utilization of
      Lignocellulosic Biomass.
AB  - Production of chemicals via fermentation has been evolving over the past 30 years
      in search of economically viable systems. Thus far, there have been few
      industrially relevant chemicals that have seen commercialization, examples being
      lactic acid and ethanol. Currently, many of these fermentation processes still
      compete with food sources. In order to reduce this competition fermentation of
      alternative feedstocks, such as lignocellulosic biomass must to be utilized.
      Hemicellulosic sugars can be employed effectively for the production of chemicals
      by incorporating nonphosphorylative metabolism. This review covers
      nonphosphorylative metabolism, the pathways and enzymes involved, as well as the
      products that have been produced using nonphosphorylative metabolism.

PMID- 29218039
TI  - The Anaerobically Induced sRNA PaiI Affects Denitrification in Pseudomonas
      aeruginosa PA14.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that can thrive by anaerobic
      respiration in the lungs of cystic fibrosis patients using nitrate as terminal
      electron acceptor. Here, we report the identification and characterization of the
      small RNA PaiI in the P. aeruginosa strain 14 (PA14). PaiI is anaerobically
      induced in the presence of nitrate and depends on the two-component system NarXL.
      Our studies revealed that PaiI is required for efficient denitrification
      affecting the conversion of nitrite to nitric oxide. In the absence of PaiI
      anaerobic growth was impaired on glucose, which can be reconciled with a
      decreased uptake of the carbon source under these conditions. The importance of
      PaiI for anaerobic growth is further underlined by the observation that a paiI
      deletion mutant was impaired in growth in murine tumors.

PMID- 29218040
TI  - Adaptation of Lactobacillus casei Zhang to Gentamycin Involves an Alkaline Shock
      Protein.
AB  - Lactobacillus (L. casei) Zhang is a koumiss-originated probiotic strain, which
      was used as a model in a long-term antibiotics-driven evolution experiment to
      reveal bacterial evolutionary dynamics; and we isolated gentamycin-resistant L.
      casei Zhang descendents. To decipher the gentamycin resistance mechanism, here we
      cultivated the parental L. casei Zhang and its descendent cells in an antibiotics
      containing environment to compare their global protein expression profiles using
      the iTRAQ-based proteomic approach. A total of 72 proteins were significantly up
      regulated (>2.0-fold, P < 0.05), whilst 32 proteins were significantly down
      regulated <-2.0-fold, P < 0.05) in the descendent line. The gentamycin-resistant
      descendent line showed elevated expression in some carbohydrates, amino acids,
      and purine metabolic pathways. Several stress-related proteins were also
      differentially expressed. Among them, one alkaline shock protein, asp23, was up
      regulated most in the gentamycin-resistant strain (21.9-fold increase compared
      with the parental strain). The asp23 gene disruption mutant was significantly
      more sensitive to gentamycin compared with the wild type, suggesting an important
      role of this gene in developing the gentamycin-resistant phenotype in L. casei.
      Our report has described the adaptation of a probiotic strain that has acquired
      antibiotics resistance through long-term antibiotics exposure at the proteome
      level, and we revealed a novel mechanism of gentamycin resistance.

PMID- 29218042
TI  - Corrigendum: Gene Expression in Class 2 Integrons Is SOS-Independent and Involves
      Two Pc Promoters.
AB  - [This corrects the article on p. 1499 in vol. 8, PMID: 28861047.].

PMID- 29218041
TI  - Mrp Antiporters Have Important Roles in Diverse Bacteria and Archaea.
AB  - Mrp (Multiple resistance and pH) antiporter was identified as a gene
      complementing an alkaline-sensitive mutant strain of alkaliphilic Bacillus
      halodurans C-125 in 1990. At that time, there was no example of a multi-subunit
      type Na+/H+ antiporter comprising six or seven hydrophobic proteins, and it was
      newly designated as the monovalent cation: proton antiporter-3 (CPA3) family in
      the classification of transporters. The Mrp antiporter is broadly distributed
      among bacteria and archaea, not only in alkaliphiles. Generally, all Mrp
      subunits, mrpA-G, are required for enzymatic activity. Two exceptions are Mrp
      from the archaea Methanosarcina acetivorans and the eubacteria Natranaerobius
      thermophilus, which are reported to sustain Na+/H+ antiport activity with the
      MrpA subunit alone. Two large subunits of the Mrp antiporter, MrpA and MrpD, are
      homologous to membrane-embedded subunits of the respiratory chain complex I,
      NuoL, NuoM, and NuoN, and the small subunit MrpC has homology with NuoK. The
      functions of the Mrp antiporter include sodium tolerance and pH homeostasis in an
      alkaline environment, nitrogen fixation in Schizolobium meliloti, bile salt
      tolerance in Bacillus subtilis and Vibrio cholerae, arsenic oxidation in
      Agrobacterium tumefaciens, pathogenesis in Pseudomonas aeruginosa and
      Staphylococcus aureus, and the conversion of energy involved in metabolism and
      hydrogen production in archaea. In addition, some Mrp antiporters transport K+
      and Ca2+ instead of Na+, depending on the environmental conditions. Recently, the
      molecular structure of the respiratory chain complex I has been elucidated by
      others, and details of the mechanism by which it transports protons are being
      clarified. Based on this, several hypotheses concerning the substrate transport
      mechanism in the Mrp antiporter have been proposed. The MrpA and MrpD subunits,
      which are homologous to the proton transport subunit of complex I, are involved
      in the transport of protons and their coupling cations. Herein, we outline other
      recent findings on the Mrp antiporter.

PMID- 29218044
TI  - Editorial: Ying and Yang Members of the Tumor Necrosis Factor Superfamily:
      Friends or Foes in Immune-Mediated Diseases and Cancer.

PMID- 29218043
TI  - Development of Novel Promiscuous Anti-Chemokine Peptibodies for Treating
      Autoimmunity and Inflammation.
AB  - Chemokines and their receptors play critical roles in the progression of
      autoimmunity and inflammation. Typically, multiple chemokines are involved in the
      development of these pathologies. Indeed, targeting single chemokines or
      chemokine receptors has failed to achieve significant clinical benefits in
      treating autoimmunity and inflammation. Moreover, the binding of host atypical
      chemokine receptors to multiple chemokines as well as the binding of chemokine
      binding proteins secreted by various pathogens can serve as a strategy for
      controlling inflammation. In this work, promiscuous chemokine-binding peptides
      that could bind and inhibit multiple inflammatory chemokines, such as CCL2, CCL5,
      and CXCL9/10/11, were selected from phage display libraries. These peptides were
      cloned into human mutated immunoglobulin Fc-protein fusions (peptibodies). The
      peptibodies BKT120Fc and BKT130Fc inhibited the ability of inflammatory
      chemokines to induce the adhesion and migration of immune cells. Furthermore,
      BKT120Fc and BKT130Fc also showed a significant inhibition of disease progression
      in a variety of animal models for autoimmunity and inflammation. Developing a
      novel class of antagonists that can control the courses of diseases by
      selectively blocking multiple chemokines could be a novel way of generating
      effective therapeutics.

PMID- 29218045
TI  - Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte
      Aggregate Formation.
AB  - Platelet/granulocyte aggregates (PGAs) increase thromboinflammation in the
      vasculature, and PGA formation is tightly controlled by the complement
      alternative pathway (AP) negative regulator, Factor H (FH). Mutations in FH are
      associated with the prothrombotic disease atypical hemolytic uremic syndrome
      (aHUS), yet it is unknown whether increased PGA formation contributes to the
      thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to
      evaluate the effects of aHUS-related mutations on FH regulation of PGA formation
      and characterize the mechanism. Utilizing recombinant fragments of FH spanning
      the entire length of the protein, we mapped the regions of FH most critical for
      limiting AP activity on the surface of isolated human platelets and neutrophils,
      as well as the regions most critical for regulating PGA formation in human whole
      blood stimulated with thrombin receptor-activating peptide (TRAP). FH domains 19
      20 were the most critical for limiting AP activity on platelets, neutrophils, and
      at the platelet/granulocyte interface. The role of FH in PGA formation was
      attributed to its ability to regulate AP-mediated C5a generation. AHUS-related
      mutations in domains 19-20 caused differential effects on control of PGA
      formation and AP activity on platelets and neutrophils. Our data indicate FH C
      terminal domains are key for regulating PGA formation, thus increased FH
      protection may have a beneficial impact on diseases characterized by increased
      PGA formation, such as cardiovascular disease. Additionally, aHUS-related
      mutations in domains 19-20 have varying effects on control of TRAP-mediated PGA
      formation, suggesting that some, but not all, aHUS-related mutations may cause
      increased PGA formation that contributes to excessive thrombosis in patients with
      aHUS.

PMID- 29218046
TI  - TLR2 Expression in Peripheral CD4+ T Cells Promotes Th17 Response and Is
      Associated with Disease Aggravation of Hepatitis B Virus-Related Acute-On-Chronic
      Liver Failure.
AB  - Th17 responses have been shown to play crucial roles in the pathogenesis of
      hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF). The
      mechanism underlying the enhanced Th17 responses in these patients remains
      largely unclear. Here we investigated toll-like receptors (TLRs) expression in
      peripheral T cells and their roles in Th17 cell differentiation and disease
      aggravation in ACLF patients. 18 healthy subjects (HS), 20 chronic HBV-infected
      (CHB) patients, and 26 ACLF patients were enrolled and examined for TLRs
      expression in peripheral blood mononuclear cells (PBMCs). The correlations of T
      cell TLR2 expression with the antigen non-specific Th17 responses and disease
      aggravation, as well as the Th17 response to TLR2 ligand stimulation were
      evaluated in ACLF patients. Compared to HS and CHB patients, ACLF patients showed
      a distinct TLRs expression pattern in PBMCs. Significantly increased TLR2
      expression in T cells was observed in ACLF patients. The TLR2 expression in CD4+
      T cells was correlated with the Th17 responses and the clinical markers for
      disease aggravation in ACLF patients. Moreover, TLR2 ligands stimulation promoted
      Th17 cell differentiation and response in PBMCs of ACLF patients. These findings
      implicate that TLR2 signaling plays critical roles in Th17 cell differentiation
      and disease aggravation of HBV-related ACLF.

PMID- 29218047
TI  - Reverse Transcriptase Mechanism of Somatic Hypermutation: 60 Years of Clonal
      Selection Theory.
AB  - The evidence for the reverse transcriptase mechanism of somatic hypermutation is
      substantial and multifactorial. In this 60th anniversary year of the publication
      of Sir MacFarlane Burnet's Clonal Selection Theory, the evidence is briefly
      reviewed and updated.

PMID- 29218048
TI  - Commentary: Belatacept Does Not Inhibit Follicular T Cell-Dependent B-Cell
      Differentiation in Kidney Transplantation.

PMID- 29218049
TI  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce
      Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell
      Line.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very
      fast progression, no diagnostic tool for the presymptomatic phase, and still no
      effective treatment of the disease. Although ALS affects motor neurons, the
      overall pathophysiological condition points out to the non-cell autonomous
      mechanisms, where astrocytes and microglia play crucial roles in the disease
      progression. We have already shown that IgG from sera of ALS patients (ALS IgG)
      induce calcium transients and an increase in the mobility of acidic vesicles in
      cultured rat astrocytes. Having in mind the role of microglia in
      neurodegeneration, and a well-documented fact that oxidative stress is one of the
      many components contributing to the disease, we decided to examine the effect of
      ALS IgG on activation, oxidative stress and antioxidative system of BV-2
      microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on
      reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to
      control IgG) induced oxidative stress (rise in nitric oxide and the index of
      lipid peroxidation) followed by release of TNF-alpha and higher antioxidative
      defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and
      glutathione reductase with a decrease of glutathione peroxidase and glutathione)
      after 24 h treatment. Both ALS IgG and control IgG showed same localization on
      the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH
      alteration were evaluated with fluorescent probes HyPer and SypHer, respectively,
      having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from
      ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal
      normalized fluorescence in the range 0.2-0.5, also inducing similar increase of
      SypHer intensity, but of a lower amplitude. None of the control IgGs induced
      changes with neither of the indicators. Acute ROS generation was detected in one
      out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena
      demonstrate the potential role of inflammatory humoral factors, IgGs, as
      potential triggers of the activation in microglia, known to occur in later stages
      of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells
      could offer a valuable molecular biomarker and/or a potential therapeutic target.

PMID- 29218050
TI  - Heme Drives Oxidative Stress-Associated Cell Death in Human Neutrophils Infected
      with Leishmania infantum.
AB  - Free heme is an inflammatory molecule capable of inducing migration and
      activation of neutrophils. Here, we examine the heme-driven oxidative stress
      associated cell death mechanisms in human neutrophils infected with Leishmania
      infantum, an etiologic agent of visceral leishmaniasis (VL). We first performed
      exploratory analyses in a population of well characterized treatment-naive VL
      patients as well as uninfected controls, who were part of previously reported
      studies. We noted a positive correlation between serum concentrations of heme
      with heme oxygenase-1 (HO-1) and lactate deydrogenase, as well as, a negative
      correlation between heme values and peripheral blood neutrophils counts.
      Moreover, in vitro infection with L. infantum in the presence of heme enhanced
      parasite burden in neutrophils, while increasing the production of reactive
      oxygen species and release of neutrophilic enzymes. Additional experiments
      demonstrated that treatment of infected neutrophils with ferrous iron (Fe+2), a
      key component of the heme molecule, resulted in increased parasite survival
      without affecting neutrophil activation status. Furthermore, stimulation of
      infected neutrophils with heme triggered substantial increases in HO-1 mRNA
      expression as well as in superoxide dismutase-1 enzymatic activity. Heme, but not
      Fe+2, induced oxidative stress-associated cell death. These findings indicate
      that heme promotes intracellular L. infantum survival via activation of
      neutrophil function and oxidative stress. This study opens new perspectives for
      the understanding of immunopathogenic mechanisms involving neutrophils in VL.

PMID- 29218051
TI  - Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of
      CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of
      Sepsis-Induced Immunosuppression.
AB  - Sepsis is the dysregulated response of the host to systemic, mostly bacterial
      infection, and is associated with an enhanced susceptibility to life-threatening
      opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs)
      secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation
      in the bone marrow and contribute to the development of immunosuppression. We
      investigated the origin of the altered DC differentiation using murine cecal
      ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow
      cells (BMC) were isolated after sham or CLP operation, the cellular composition
      was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From
      24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10.
      In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in
      a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC
      in vitro reversed the increased IL-10 secretion of subsequently differentiating
      BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow
      after CLP required the function of sphingosine 1-phosphate receptors and C-C
      chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but
      was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were
      identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype
      according to their increased expression of MHC class II and CD86. A
      redistribution of CD4+ pDCs from MHC class II- to MHC class II+ cells concomitant
      with enhanced expression of CD11c finally led to the rise in the number of
      CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of
      septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+
      pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs
      toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial
      sepsis, CD4+ pDCs are activated in the bone marrow and induce functional
      reprogramming of differentiating BMDC toward an immunosuppressive phenotype.

PMID- 29218053
TI  - Marker Development for Phylogenomics: The Case of Orobanchaceae, a Plant Family
      with Contrasting Nutritional Modes.
AB  - Phylogenomic approaches, employing next-generation sequencing (NGS) techniques,
      have revolutionized systematic and evolutionary biology. Target enrichment is an
      efficient and cost-effective method in phylogenomics and is becoming increasingly
      popular. Depending on availability and quality of reference data as well as on
      biological features of the study system, (semi-)automated identification of
      suitable markers will require specific bioinformatic pipelines. Here, we
      established a highly flexible bioinformatic pipeline, BaitsFinder, to identify
      putative orthologous single copy genes (SCGs) and to construct bait sequences in
      a single workflow. Additionally, this pipeline has been constructed to be able to
      cope with challenging data sets, such as the nutritionally heterogeneous plant
      family Orobanchaceae. To this end, we used transcriptome data of differing
      quality available for four Orobanchaceae species and, as reference, SCG data from
      monkeyflower (Erythranthe guttata, syn. Mimulus g.; 1,915 genes) and tomato
      (Solanum lycopersicum; 391 genes). Depending on whether gaps were permitted in
      initial blast searches of the four Orobanchaceae species against the reference,
      our pipeline identified 1,307 and 981 SCGs with average length of 994 bp and 775
      bp, respectively. Automated bait sequence construction (using 2* tiling) resulted
      in 38,170 and 21,856 bait sequences, respectively. In comparison to the recently
      published MarkerMiner 1.0 pipeline BaitsFinder identified about 1.6 times as many
      SCGs (of at least 900 bp length). Skipping steps specific to analyses of
      Orobanchaceae, BaitsFinder was successfully used in a group of non-parasitic
      plants (three Asteraceae species and, as reference, SCG data from Arabidopsis
      thaliana based on previously compiled SCGs). Thus, BaitsFinder is expected to be
      broadly applicable in groups, where only transcriptomes or partial genome data of
      differing quality are available.

PMID- 29218055
TI  - Editorial: Plants' Responses to Novel Environmental Pressures.

PMID- 29218054
TI  - Excessive Cellular S-nitrosothiol Impairs Endocytosis of Auxin Efflux Transporter
      PIN2.
AB  - S-nitrosoglutathione reductase (GSNOR1) is the key enzyme that regulates cellular
      levels of S-nitrosylation across kingdoms. We have previously reported that loss
      of GSNOR1 resulted in impaired auxin signaling and compromised auxin transport in
      Arabidopsis, leading to the auxin-related morphological phenotypes. However, the
      molecular mechanism underpinning the compromised auxin transport in gsnor1-3
      mutant is still unknown. Endocytosis of plasma-membrane (PM)-localized efflux PIN
      proteins play critical roles in auxin transport. Therefore, we investigate
      whether loss of GSNOR1 function has any effects on the endocytosis of PIN-FORMED
      (PIN) proteins. It was found that the endocytosis of either the endogenous PIN2
      or the transgenically expressed PIN2-GFP was compromised in the root cells of
      gsnor1-3 seedlings relative to Col-0. The internalization of PM-associated PIN2
      or PIN2-GFP into Brefeldin A (BFA) bodies was significantly reduced in gsnor1-3
      upon BFA treatment in a manner independent of de novo protein synthesis. In
      addition, the exogenously applied GSNO not only compromised the endocytosis of
      PIN2-GFP but also inhibited the root elongation in a concentration-dependent
      manner. Taken together, our results indicate that, besides the reduced PIN2
      level, one or more compromised components in the endocytosis pathway could
      account for the reduced endocytosis of PIN2 in gsnor1-3.

PMID- 29218052
TI  - Spoiling for a Fight: B Lymphocytes As Initiator and Effector Populations within
      Tertiary Lymphoid Organs in Autoimmunity and Transplantation.
AB  - Tertiary lymphoid organs (TLOs) develop at ectopic sites within chronically
      inflamed tissues, such as in autoimmunity and rejecting organ allografts. TLOs
      differ structurally from canonical secondary lymphoid organs (SLOs), in that they
      lack a mantle zone and are not encapsulated, suggesting that they may provide
      unique immune function. A notable feature of TLOs is the frequent presence of
      structures typical of germinal centers (GCs). However, little is known about the
      role of such GCs, and in particular, it is not clear if the B cell response
      within is autonomous, or whether it synergizes with concurrent responses in SLOs.
      This review will discuss ectopic lymphoneogenesis and the role of the B cell in
      TLO formation and subsequent effector output in the context of autoimmunity and
      transplantation, with particular focus on the contribution of ectopic GCs to
      affinity maturation in humoral immune responses and to the potential breakdown of
      self-tolerance and development of humoral autoimmunity.

PMID- 29218057
TI  - Lessons from the Human Genome Project: Modesty, Honesty, and Realism.

PMID- 29218056
TI  - Respiratory Burst Oxidase Homolog Gene A Is Crucial for Rhizobium Infection and
      Nodule Maturation and Function in Common Bean.
AB  - Reactive oxygen species (ROS) produced by respiratory burst oxidase homologs
      (RBOHs) regulate numerous plant cell processes, including the symbiosis between
      legumes and nitrogen-fixing bacteria. Rapid and transient ROS production was
      reported after Phaseolus vulgaris root hairs were treated with Nod factors,
      indicating the presence of a ROS-associated molecular signature in the symbiosis
      signaling pathway. Rboh is a multigene family containing nine members (RbohA-I)
      in P. vulgaris. RNA interference of RbohB suppresses ROS production and
      attenuates rhizobial infection thread (IT) progression in P. vulgaris root hairs.
      However, the roles of other Rboh members in symbiotic interactions are largely
      unknown. In this study, we characterized the role of the NADPH oxidase-encoding
      gene RbohA (Phvulv091020621) in the P. vulgaris-Rhizobium tropici symbiosis. The
      spatiotemporal activity of the RbohA promoter colocalized with growing ITs and
      was associated with vascular bundles in developing nodules. Subcellular
      localization studies indicated that RBOHA was localized in the plasma membrane of
      P. vulgaris root hairs. After rhizobial inoculation, PvRBOHA was mainly
      distributed in the infection pocket and, to a lesser extent, throughout the IT.
      In PvRbohA RNAi lines, the rhizobial infection events were significantly reduced
      and, in successful infections, IT progression was arrested within the root hair,
      but did not impede cortical cell division. PvRbohA-RNAi nodules failed to fix
      nitrogen, since the infected cells in the few nodules formed were empty. RbohA
      dependent ROS production and upregulation of several antioxidant enzymes was
      attenuated in rhizobia-inoculated PvRbohA-RNAi roots. These combined results
      indicate that PvRbohA is crucial for effective Rhizobium infection and its
      release into the nodule cells. This oxidase is partially or indirectly required
      to promote nodule organogenesis, altering the expression of auxin- and cyclin
      related genes and genes involved in cell growth and division.

PMID- 29218058
TI  - Assessment of the effect of three-dimensional mantle density heterogeneity on
      earth rotation in tidal frequencies.
AB  - In this paper we report the assessment of the effect of the three-dimensional
      (3D) density heterogeneity in the mantle on Earth Orientation Parameters (EOP)
      (i.e., the polar motion, or PM, and the length of day, or LOD) in the tidal
      frequencies. The 3D mantle density model is estimated based upon a global S-wave
      velocity tomography model (S16U6L8) and the mineralogical knowledge derived from
      laboratory experiment. The lateral density variation is referenced against the
      Preliminary Reference Earth Model (PREM). Using this approach the effects of the
      heterogeneous mantle density variation in all three tidal frequencies (zonal long
      periods, tesseral diurnal, and sectorial semidiurnal) are estimated in both PM
      and LOD. When compared with mass or density perturbations originated on the
      earth's surface such as the oceanic and barometric changes, the heterogeneous
      mantle only contributes less than 10% of the total variation in PM and LOD in
      tidal frequencies. Nevertheless, including the 3D variation of the density in the
      mantle into account explained a substantial portion of the discrepancy between
      the observed signals in PM and LOD extracted from the lump-sum values based on
      continuous space geodetic measurement campaigns (e.g., CONT94) and the computed
      contribution from ocean tides as predicted by tide models derived from satellite
      altimetry observations (e.g., TOPEX/Poseidon). In other word, the difference of
      the two, at all tidal frequencies (long-periods, diurnals, and semi-diurnals)
      contains contributions of the lateral density heterogeneity of the mantle. Study
      of the effect of mantle density heterogeneity effect on torque-free earth
      rotation may provide useful constraints to construct the Reference Earth Model
      (REM), which is the next major objective in global geophysics research beyond
      PREM.

PMID- 29218060
TI  - Our Life through Device.

PMID- 29218059
TI  - Warming alters the energetic structure and function but not resilience of soil
      food webs.
AB  - Climate warming is predicted to alter the structure, stability, and functioning
      of food webs1-5. Yet, despite the importance of soil food webs for energy and
      nutrient turnover in terrestrial ecosystems, warming effects on these food webs
      particularly in combination with other global change drivers-are largely unknown.
      Here, we present results from two complementary field experiments testing the
      interactive effects of warming with forest canopy disturbance and drought on
      energy fluxes in boreal-temperate ecotonal forest soil food webs. The first
      experiment applied a simultaneous above- and belowground warming treatment
      (ambient, +1.7 degrees C, +3.4 degrees C) to closed canopy and recently clear-cut
      forest, simulating common forest disturbance6. The second experiment crossed
      warming with a summer drought treatment (-40% rainfall) in the clear-cut
      habitats. We show that warming reduces energy fluxes to microbes, while forest
      canopy disturbance and drought facilitates warming-induced increases in energy
      flux to higher trophic levels and exacerbates reductions in energy flux to
      microbes, respectively. Contrary to expectations, we find no change in whole
      network resilience to perturbations, but significant losses of ecosystem
      functioning. Warming thus interacts with forest disturbance and drought, shaping
      the energetic structure of soil food webs and threatening the provisioning of
      multiple ecosystem functions in boreal-temperate ecotonal forests.

PMID- 29218061
TI  - A Comparative Study of Efficacy and Safety of Two Eradication Regimens for
      Helicobacter pylori Infection.
AB  - Introduction: Helicobacter pylori infection is one of the most frequent diseases
      around the world, affecting about half of the world population. The infection is
      known to be associated with upper gastrointestinal diseases. The aim of this
      paper is to identify which of the following two first-line therapy options (ECA
      vs ECM - see abbreviations below) is more efficient and to assess the improvement
      in the quality of life among these patients. Material and Methods: 96 patients
      with proven Helicobacter pylori infection were divided in two treatment groups,
      as follows: 47 patients received a 10-day triple therapy with esomeprazole 80
      mg/day, amoxicillin 2000 mg/day and clarithromycin 1000 mg/day (ECA) and the rest
      of 49 received a 10-day sequential therapy: esomeprazole 40 mg and amoxicillin
      1000 mg twice daily for five days, followed by esomeprazole 40 mg, clarithromycin
      500 mg and metronidazole 500 mg (ECM) twice daily for another five days.
      Assessment of Helicobacter pylori infection was performed using the stool antigen
      test one month after the patient finished therapy. At the beginning of the study
      and at the follow-up visit, every subject was asked to complete the
      Gastrointestinal Quality of Life Index (GIQLI). Results: Twenty three patients
      did not come for the follow-up visit (24% drop-out rate). The ECA therapy group
      had an efficacy rate of 94%, while the rate of the ECM treated group was 95% (per
      protocol analysis). There was no significant difference regarding the baseline
      characteristics between the two groups. The entire group treatment tolerability
      was approximately 85%, with no statistical difference between groups (p-value =
      0.824). Quality of life improvement was 11.18 points in the ECA treated group and
      13.4 points in the ECM treated group (p=NS). Regarding the quality of life
      improvement, the results were positive, irrespective of type of peptic disease,
      but the most important results were obtained in peptic ulcer disease, functional
      dyspepsia and chronic gastritis. Conclusions: Both ECA and ECM regimens are
      almost equally effective in Helicobacter pylori eradication and significantly
      improve the quality of life irrespective of type of peptic disease. The
      limitation of this study was the significant drop-out rate (24%) that may have
      overestimated the results.

PMID- 29218062
TI  - Preliminary Study Regarding the Association between Tumor Necrosis Factor Alpha
      Gene Polymorphisms and Childhood Idiopathic Nephrotic Syndrome in Romanian
      Pediatric Patients.
AB  - Background: Childhood idiopathic nephrotic syndrome (INS) is one of the most
      common glomerular diseases, characterized by heavy proteinuria, hypoalbuminemia,
      dyslipidemia and generalized edema. Although some progresses were made regarding
      the pathogenesis of this disease, there are a lot of questions still left
      unanswered. Some of them involve the implications of several cytokines, including
      tumor necrosis factor alpha (TNF-alpha), in the development and clinical course
      of INS. Objective: Our objective was to analyze the role of two single nucleotide
      polymorphisms of TNF-alpha gene in the development of pediatric INS and their
      implication in the response to corticosteroid therapy. Material and methods:
      Seventy patients with INS and 159 healthy controls were included in this study.
      They were analyzed for TNF-alpha gene polymorphisms by using polymerase chain
      reaction. The two SNPs (rs1799724/-857C/T and rs1800629/-308G/A) were genotyped
      by TaqMan Genotyping Assays, association tests were performed and p values <0.05
      were considered significant. Results: Minor alleles frequencies were 15.72% in
      INS patients versus 18.55% in controls for 857*T allele and 11.43% in INS versus
      13.2% in controls for 308*A allele. Although the minor alleles were more frequent
      in controls than in patients, the difference was not statistically significant
      (p=0.46, OR=0.818 and p=0.59, OR=0.848).Analyzing the response to corticosteroid
      therapy, we found a low frequency of 857*T allele in steroid resistant patients
      (9.09%) compared to steroid sensitive patients (16.95%) and controls (18.55%).
      Regarding 308*A allele, the frequencies were 18.18% in the corticoresistant group
      and 10.17% in the corticosensitive one. None of them was statistically
      significant (p>0.05). Conclusions: We conclude that neither -857C/T, nor-308G/A
      polymorphisms of TNF-alpha gene are associated with the susceptibility and
      response to steroid treatment of INS in our population. Given the small sample
      size used, future studies are necessary to clarify the results observed in the
      present study.

PMID- 29218063
TI  - Analysis of the Most Common Three MEFV Mutations in 630 Patients with Familial
      Mediterranean Fever in Iranian Azeri Turkish Population.
AB  - Introduction: The aim of the present study was to determine the frequency of
      M694V, M680I and V726A mutations of the MEFV gene in 630 Azeri Turkish patients
      with family Mediterranean fever. Material and Methods: The MEFV gene mutations
      were detected using allele-specific oligonucleotide polymerase chain reaction.
      Outcomes: 630 cases with a mean age +/- SD of 28.54+/-16.54 ranging from 2.5 to
      76 years old including 268 (42.54%) males and 362 (57.46%) females, were tested.
      Nineteen patients were homozygote for one mutation (3.02%), 127 were heterozygote
      for one mutation (20.2%) and 18 were compound heterozygote for two mutations
      (2.86%). Mutation analysis confirmed that the most common mutation was M694V 109
      (8.65%). V726A and M680I mutations accounted for 4.44% of the alleles; V726A 32
      (2.54%) and M680I 24 (1.9%). In this study, compound heterozygote for M694V and
      V726A, M694V and M680I, and V726A and M680I mutations were found in 1.43%, 0.79%,
      and 0.63% from West Azerbaijan province in exon 10. Mutation was found in 164
      (26.03%) of cases regarding analysis of the three most common MEFV mutations, but
      in 466 (73.97%) of cases, no mutation was detected. Among our samples, the
      frequencies of mutant genotypes were 15 (2.38%), 1 (0.15%), 3 (0.47%), 9 (1.42%),
      4 (0.63%) and 5 (0.79%), regarding M694V/M694V, M680I/M680I, V726A/V726A, M694V/
      V726A, M680I/ V726A and M680I/ M694V, respectively. In our samples, 79 (12.53%),
      26 (4.12%), and 22 (3.49%) cases had M694V/normal, V726A/normal, and M680I/normal
      genotypes regarding M694V, V726A, and M680I mutations, respectively. Conclusions:
      The M694V mutation is the most common risk factor for family Mediterranean fever
      in our group.

PMID- 29218064
TI  - Non-diabetic Hyperglycemia and Some of Its Correlates in ICU Hospitalized
      Patients Receiving Enteral Nutrition.
AB  - Introduction: Hyperglycemia is a common occurrence in critically ill patients,
      and its prevalence in patients receiving nutritional support is much higher than
      in other patients. The non-diabetic form is associated with more undesirable
      outcomes. This study was performed to determine the prevalence of non-diabetic
      hyperglycemia and its correlates in patients receiving enteral nutrition.
      Material and Methods: This cross-sectional study was performed between March and
      December 2015. Seven hundred forty eight (748) patients were reviewed to see if
      they met the inclusion criteria. After random sequence numbering, 414 patients
      who were eligible for further assessment and data gathering were selected.
      Hyperglycemia was defined as the blood glucose levels higher than either 126
      mg/dL, in the fasting state, or 180 mg/dL, in a random state. Blood glucose was
      measured by an ACCU-CHECK glucometer (Roche diagnostics, Mannheim, Germany) three
      times, after ICU admission, in both fasting and random state. A pre-prepared form
      was used to extract data from hospital records. Data analysis was performed by
      SPSS 21 software. Results: In this group of hospitalized patients, the prevalence
      of non-diabetic hyperglycemia was 14/49 (60/414). In the hyperglycemic subgroup,
      mean FBS was 228.00+/-36.42, mean random BS was 183.19+/-43.94 and mean blood
      sugar on the first day of hospitalization was 203.60 +/- 60.79. The mean age of
      patients was 56.64+/-19.79 years and the mean duration of hospitalization was
      19.24+/-15.33 days. There was no significant relationship between enteral
      nutrition feeding volume and hyperglycemia. Majorly, patients aged above 60 years
      were hyperglycemic. The prevalence was higher in men than in women. Most patients
      were internal cases, but with the highest prevalence of hyperglycemia in surgical
      patients. Conclusions: Since among different studied variables just diagnosed
      disease and the level of provided calorie showed significant differences between
      subgroup categories, so it can be suggested that designing on-time appropriate
      management programs based them can be effective on the administration of non
      diabetic hyperglycemia and its undesirable consequences in such patients.

PMID- 29218065
TI  - Acute Myocardial Injury in a Child with Duchenne Muscular Dystrophy: Pulse
      Steroid Therapy?
AB  - Heart implication in Duchenne muscular dystrophy usually is present in the form
      of dilated cardiomyopathy, manifested as heart failure and arrhythmias. To delay
      progression, including heart deterioration, prednisone is recommended as
      preventive treatment. We report the case of an 11-year-old boy diagnosed with
      Duchenne muscular dystrophy at the age of seven, who was on preventive treatment
      with oral prednisone (0.75 mg/kg/day) and beta blocker (metoprolol, 1 mg/kg/day).
      Suddenly, the patient presented acute chest pain, vomiting and sweating. The
      electrocardiogram showed ST elevation in inferior leads. Troponin T was increased
      to 30814 pg/ml (normal values <14 pg/mL). The echocardiography revealed reduced
      contractility of the posteroinferior wall of the left ventricle. After excluding
      coronary implications by coronary angiography, we increased the oral prednisone
      to 1.4 mg/kg/day for five days and added enalapril (0.5 mg/kg/day, po). The
      response was positive, with a rapid decrease of the troponin T value to 3186
      pg/mL in five days and gradual recovery of myocardial contractility afterwards.

PMID- 29218066
TI  - Arterial Stiffness and Hypertension - Which Comes First?
AB  - Arterial hypertension is one of the traditional risk factors involved in the
      development of cardiovascular events, while arterial stiffness is an independent
      predictor of cardiovascular disease in patients with hypertension. It seems that
      the risk factors involved in the pathology of uncontrolled hypertension are
      similar to those that contribute to the development of arterial stiffness. After
      evidence showed that arterial stiffness is an independent prognostic factor for
      the occurrence of cardiovascular events in patients with arterial hypertension,
      the importance of assessing arterial stiffness was recognized in a document
      drafted by the European Society of Hypertension in 2007. Many factors, some still
      insufficiently studied, are involved in the development and worsening of arterial
      stiffness, especially in patients with certain comorbidities (diabetes,
      hypertension, chronic kidney disease). The evaluation of pulse wave velocity
      (PWV) remains the gold standard for non-invasive assessment of arterial
      stiffness. It seems that changes in terms of lifestyle and drug therapy have some
      positive effects on improving arterial stiffness, but further studies are needed
      to prove this concept. Our review aims to highlight the novelty of the
      mechanisms, the assessment methods, some of the clinical aspects, as well as the
      therapeutic implications of arterial stiffness, especially in patients with
      hypertension.

PMID- 29218068
TI  - Prostheses Used in Laparoscopic Inguinal Hernia Repair: Biocompatibility,
      Postoperative Complications and Quality of Life - Review of the Literature.
AB  - INTRODUCTION: There is a continuous concern about meshes used in laparoscopic
      inguinal hernia repair, which mainly relates to their biocompatibility and
      ability to decrease postoperative complications and recurrence rate; in other
      words, efforts are made to find the "ideal" prosthesis. OBJECTIVES: To evaluate
      different prostheses used in laparoscopic inguinal hernia repair in terms of
      biocompatibility, postoperative complications, recurrence rate and quality of
      life, so that all the features could lead us to the "ideal" mesh. MATERIAL AND
      METHOD: Randomized controlled trials, reviews, prospective and retrospective
      studies, retrospective cross-sectional and experimental studies on animals
      published between 2000 and 2016 were analysed with respect to several features of
      a mesh: biocompatibility, postoperative complications, recurrence rate and
      quality of life. OUTCOMES: The most common comparison is between heavy-weight and
      light-weight mesh used in laparoscopic inguinal hernia repair. Experimental
      studies try to discover the "ideal" prosthesis, which could provide improved
      biocompatibility, low postoperative complications, decreased recurrence rate and
      good quality of life. The most commonly used mesh that meats the characteristics
      of an "ideal" prosthesis is a light-weight monofilament macroporous polypropylene
      mesh, with a minimum tensile strength >16 N/cm2, measuring 10x15 cm. CONCLUSIONS:
      Published data show that the "ideal" prosthesis used in laparoscopic inguinal
      hernia repair has not been discovered yet. Regarding heavy- or light-weight
      meshes, there is no significant effect on recurrence, acute or chronic pain,
      incidence of seroma or return to daily activity and quality of life (1).

PMID- 29218067
TI  - Perceived Age and Life Style. The Specific Contributions of Seven Factors
      Involved in Health and Beauty.
AB  - OBJECTIVES: The skin is a dynamic, visible organ, showing the most obvious signs
      of aging. The mechanisms of extrinsic aging, most of them presented in this
      paper, are currently well known and also the only ones that can be counteracted.
      Therefore, the transition of this knowledge in the general population is of the
      most importance, in order to introduce healthy aging strategies, to prevent the
      development of chronic or malignant diseases and psychological burden related to
      old age. MATERIALS AND METHODS: A thorough review of the literature has been
      performed in order to identify the main factors involved in skin health and
      aging. OUTCOMES: This concept article represents a compilation of seven anti
      ageing directions regarding major factors involved in health, aging and beauty,
      respectively sun, sugar, smoking, skin care, stress, sleep and second (the
      passage of time), easy to comprehend by the general public but sustained by a
      strong scientific documentation. CONCLUSIONS: Despite its final destination,
      every quality concept has to pass through academic purgatory as, once accepted,
      it comes to respond to ever more educated society's demands in terms of anti
      ageing.

PMID- 29218069
TI  - Down Syndrome - Genetics and Cardiogenetics.
AB  - During the last years, Down syndrome has been the focus of special attention.
      Down syndrome is a genetic disorder characterized by distinct physical features
      and some degree of cognitive disability. Patients with Down syndrome also present
      many other congenital anomalies. The mapping for phenotypes to specific regions
      of chromosome 21 permits to identify which genes (or small regions) contribute to
      the phenotypic features of Down syndrome and thus, to understand its
      pathogenesis. Mainly there are three cytogenetic forms of Down syndrome: free
      trisomy 21, mosaic trisomy 21 and robertsonian translocation trisomy 21. Prenatal
      and postnatal testing has become commonly used to diagnose different cases
      presenting the same pathology. Early clinical diagnosis is extremely important
      for patient prognosis. Lately, advances in Down syndrome research have been
      registered, but little is known about cardiovascular phenotype in Down syndrome.
      About half of patients with Down syndrome have congenital heart disease, and
      atrioventricular septal defects are the most common defects found. Basic research
      on Down syndrome is now rapidly accelerating, using new genomic technologies.
      There were many studies performed to identify a correlation between genotype and
      phenotype in Down syndrome.

PMID- 29218070
TI  - Radiographic Evaluation of Alignment Following TKA, a Systematic Review.
AB  - Postoperative assessment is of paramount importance in primary total knee
      arthroplasty. A thorough postoperative analysis helps the surgeon anticipate any
      postoperative potential issues and correlate the preoperative planning with the
      postoperative result, and provides better understanding of the importance of
      surgical principles of primary total knee arthroplasty. In addition,
      postoperative analysis helps the surgeon understand surgical errors and improve
      future outcomes. Standard radiographs, with a known magnification, should be
      obtained for postoperative total knee arthroplasty evaluation. Although imaging
      evaluation of knee arthroplasty is usually limited to conventional radiographs,
      examples of the utility of computed tomography are also illustrated, and
      suggested imaging strategies discussed.

PMID- 29218071
TI  - Composite Agency: Semiotics of Modularity and Guiding Interactions.
AB  - Principles of constructivism are used here to explore how organisms develop
      tools, subagents, scaffolds, signs, and adaptations. Here I discuss reasons why
      organisms have composite nature and include diverse subagents that interact in
      partially cooperating and partially conflicting ways. Such modularity is
      necessary for efficient and robust functionality, including mutual construction
      and adaptability at various time scales. Subagents interact via material and
      semiotic relations, some of which force or prescribe actions of partners. Other
      interactions, which I call "guiding", do not have immediate effects and do not
      disrupt the evolution and learning capacity of partner agents. However, they
      modify the extent of learning and evolutionary possibilities of partners via
      establishment of scaffolds and constraints. As a result, subagents construct
      reciprocal scaffolding for each other to rebalance their communal evolution and
      learning. As an example, I discuss guiding interactions between the body and mind
      of animals, where the pain system adjusts mind-based learning to the physical and
      physiological constraints of the body. Reciprocal effects of mind and behaviors
      on the development and evolution of the body includes the effects of Lamarck and
      Baldwin.

PMID- 29218072
TI  - Spatial Multiresolution Analysis of the Effect of PM2.5 on Birth Weights.
AB  - Fine particulate matter (PM2.5) measured at a given location is a mix of
      pollution generated locally and pollution traveling long distances in the
      atmosphere. Therefore, the identification of spatial scales associated with
      health effects can inform on pollution sources responsible for these effects,
      resulting in more targeted regulatory policy. Recently, prediction methods that
      yield high-resolution spatial estimates of PM2.5 exposures allow one to evaluate
      such scale-specific associations. We propose a two-dimensional wavelet
      decomposition that alleviates restrictive assumptions required for standard
      wavelet decompositions. Using this method we decompose daily surfaces of PM2.5 to
      identify which scales of pollution are most associated with adverse health
      outcomes. A key feature of the approach is that it can remove the purely temporal
      component of variability in PM2.5 levels and calculate effect estimates derived
      solely from spatial contrasts. This eliminates the potential for unmeasured
      confounding of the exposure - outcome associations by temporal factors, such as
      season. We apply our method to a study of birth weights in Massachusetts, U.S.A
      from 2003-2008 and find that both local and urban sources of pollution are
      strongly negatively associated with birth weight. Results also suggest that
      failure to eliminate temporal confounding in previous analyses attenuated the
      overall effect estimate towards zero, with the effect estimate growing in
      magnitude once this source of variability is removed.

PMID- 29218073
TI  - Interconversion between Free Charges and Bound Excitons in 2D Hybrid Lead Halide
      Perovskites.
AB  - The optoelectronic properties of hybrid perovskites can be easily tailored by
      varying their components. Specifically, mixing the common short organic cation
      (methylammonium (MA)) with a larger one (e.g., butyl ammonium (BA)) results in 2
      dimensional perovskites with varying thicknesses of inorganic layers separated by
      the large organic cation. In both of these applications, a detailed understanding
      of the dissociation and recombination of electron-hole pairs is of prime
      importance. In this work, we give a clear experimental demonstration of the
      interconversion between bound excitons and free charges as a function of
      temperature by combining microwave conductivity techniques with photoluminescence
      measurements. We demonstrate that the exciton binding energy varies strongly
      (between 80 and 370 meV) with the thickness of the inorganic layers.
      Additionally, we show that the mobility of charges increases with the layer
      thickness, in agreement with calculated effective masses from electronic
      structure calculations.

PMID- 29218074
TI  - Autophagy in endometriosis.
AB  - Endometriosis (EMS) is a common gynecologic disease that causes chronic pelvic
      pain, dysmenorrhea, and infertility in women. The doctrine of menstruation back
      flow planting and defects in the immune system are well known and widely
      accepted. In recent years, increasing studies have been focused on the role of
      autophagy in EMS, and have shown that autophagy plays a vital role in EMS.
      Autophagy, which is known as the non-apoptotic form of programmed cell death
      induced by a large number of intracellular/extracellular stimuli, is the major
      cellular pathway for the degradation of long-lived proteins and cytoplasmic
      organelles in eukaryotic cells. Autophagy commonly refers to macroautophagy,
      which is characterized by autophagosomes (double-membrane vesicles). In normal
      endometrial tissues, autophagy is induced in glandular epithelial and stromal
      cells throughout the menstrual cycle. However, aberrant autophagy occurs in the
      eutopic endometrium and ectopic endometriotic foci, which contributes to the
      pathogenesis of EMS by promoting the hyperplasia of endometriotic tissues and
      stromal cells, restricting apoptosis, and inducing abnormal immune responses.
      Consistent with changes in autophagy levels between normal endometria, eutopic
      and ectopic endometria from patients with EMS, the altered expression of
      autophagy-related genes (ATGs) is also observed. Currently, many factors are
      involved in the aberrant autophagy of endometriotic tissues, including female
      hormones, certain drugs, hypoxia, and oxidative stress. Therefore, studies
      focusing on autophagy may uncover a new potential treatment for EMS. The aim of
      this review is to discuss the role of aberrant autophagy in EMS and to explore
      the potential value of autophagy as a target for EMS therapy.

PMID- 29218076
TI  - 14-3-3 proteins: an important regulator of autophagy in diseases.
AB  - Autophagy is a cell digestion process that determines cell fate by promoting cell
      survival or inducing cell death in a cell context-dependent manner. Several
      classical signaling pathways, such as phosphoinositide-3-kinase and mammalian
      target of rapamycin, tightly regulate autophagy. 14-3-3 proteins regulate various
      signaling pathways by phosphorylation-dependent binding with partner proteins. 14
      3-3 proteins also regulate autophagy by binding with autophagy-related proteins
      such as Beclin-1 and hVPS34. This review summarizes the role of 14-3-3 proteins
      in the control of autophagy in cancer, neurodegenerative diseases and other
      pathological conditions.

PMID- 29218075
TI  - IL-32theta: a recently identified anti-inflammatory variant of IL-32 and its
      preventive role in various disorders and tumor suppressor activity.
AB  - Interleukin-32 theta (IL-32theta) is newly identified isoform of IL-32 which
      plays a vital role in inflammatory responses. Like IL-32alpha and IL-32beta, IL
      32theta isoform acts as an intracellular inflammatory modulator. It results in
      reduction of IL-1beta production by attenuating the expression of PU.1 and
      inhibition of monocytes differentiation into macrophages. IL-32theta hinders TNF
      alpha expression by inhibiting p38 MAPK and inhibitor of kappaB (IkappaB) as
      well. It also reserved STAT3-ZEB1 pathway leading to the inhibition of epithelial
      mesenchymal transition (EMT) and stemness. Hence, it can be concluded that IL
      32theta is an anti-inflammatory cytokine that can act as a tumor suppressor and
      can play vital role in colon cancer therapies. IL-32theta also plays a crucial
      role in immune system responses and cellular differentiation during disease
      pathogenesis. To our best knowledge this is the first ever review to condense the
      importance, precise mode of action in disease progression and latent remedial
      implications of IL-32theta in several inflammatory disorders.

PMID- 29218077
TI  - Long noncoding RNAs: a new regulatory code in osteoarthritis.
AB  - It is reported that long noncoding RNAs (lncRNAs) were expressed aberrantly in
      cartilage of osteoarthritis (OA). Current evidence indicates that lncRNAs not
      only serve as positive or negative regulators of OA, but also crosstalk with
      multiple potential targets to impact on the critical events in OA process. This
      review summarized the lncRNAs identified in OA to date, discussed their influence
      on the survival of chondrocytes and synoviocytes, arthritis-associated factors,
      and angiogenesis, and indicated the potential in diagnosis, therapy, and
      prognosis.

PMID- 29218079
TI  - VEGF-C mediated enhancement of lymphatic drainage reduces intestinal inflammation
      by regulating IL-9/IL-17 balance and improving gut microbiota in experimental
      chronic colitis.
AB  - BACKGROUND: Inflammation-associated lymphangiogenesis (IAL) induced by vascular
      endothelial growth factor (VEGF)-C/VEGF receptor-3 (VEGFR-3) pathway plays a
      crucial role in chronic intestinal inflammation. This study aimed to investigate
      the effects of VEGF-C mediated enhancement of lymphatic drainage on the
      intestinal inflammation in experimental chronic colitis (CC) and the potential
      mechanism was explored. METHODS: Mouse CC model was established by three cycles
      of 2% DSS administration for 5 days following water administration for 5 days. CC
      mice were injected via the tail vein with AD-VEGF-C-EGFP (VEGF-C+DSS group) or AD
      EGFP (AD-EGFP group) at the end of each cycle and animals in control group were
      given access to drinking water only. Disease activity index (DAI), lymphatic
      vessel density (LVD), colonic cytokines, Th9 cells (CD3+ cells) and CD68+
      macrophage infiltration, and lymph flow were detected. Fresh feces were collected
      and processed for DNA extraction and MiSeq Illumina sequencing of V4 region of
      bacterial 16S rRNA gene. Alpha- and beta diversities and compositional
      differences at phylum and genus levels were determined in intestinal microbiota.
      RESULTS: AD-VEGF-C treatment significantly reduced colon inflammation, elevated
      the increase in lymph drainage, decreased CD68+ macrophages and CD3+ T cells (Th9
      cells), reduced IL-9, and increased IL-17 in colon mucosa when compared with DSS
      mice. In addition, VEGF-C treated mice showed significantly increased the
      abundance of Bacterioidate and decreased Firmicutes at phylum level in fecal
      samples. CONCLUSION: VEGF-C improves intestinal inflammation by enhancing
      lymphatic drainage, reducing intestinal Th9 cells, regulating intestinal IL-9/IL
      17 balance and increasing intestinal Bacterioidate abundance in CC mice.

PMID- 29218078
TI  - Extendin-4 protects kidney from acute ischemia-reperfusion injury through
      upregulation of NRF2 signaling.
AB  - This study tested the hypothesis that exendin-4 (Ex4) protects kidneys against
      ischemia-reperfusion (IR) injury mainly through upregulation of nuclear-factor
      erythroid 2-related factor 2 (Nrf2) signaling and downregulation of oxidative
      stress. Male-adult Sprague-Dawley rats (n=24) were equally divided into group 1
      (sham-operated control), group 2 [IR only, ischemia (1 h)/reperfusion (72 h)] and
      group 3 (IR-Ex4, 10 MUg/kg at 30 min, 24 h, 48 h after IR procedure). The in
      vitro study demonstrated that the protein expressions of phosphorylated (p)-Akt
      and Nrf2 were significantly progressively increased at time points of 0/0.5/1/3 h
      and 0/0.5/1/3/6/12/24 h, respectively in NRK-52E cells co-cultured with Ex4 (20
      nM) (all P<0.0001). Additionally, the protein expressions of NOX-1/NOX2 were
      significantly increased, whereas p-Akt was significantly decreased in NRK-52E
      cells co-cultured with P-cresol (200 MUM) that were significantly reversed after
      Ex4 treatment (all P<0.0001). As compared with baseline, the creatinine level,
      left/right kidney weight and MCP-1-positively stained area in the kidney
      parenchyma were significantly increased at 24 h after the IR procedure and
      significantly progressively decreased after that (all P<0.0001). By 27 h after
      IR, creatinine level/MCP-1 + area was significantly higher in group 2 than in
      groups 1 and 3, and significantly higher in group 3 than in group 1 (all
      P<0.0001). The numbers of Nrf2 +/NQO-1 + cells/SOD activity in kidney parenchyma
      were significantly lower in group 2 than in groups 1 and 3, and significantly
      lower in group 1 than in group 3 (all P<0.0001). In conclusion, Ex4 protected
      kidney from IR injury through upregulating antioxidants and downregulating
      inflammation/oxidative stress.

PMID- 29218080
TI  - Whether CD44 is an applicable marker for glioma stem cells.
AB  - Glioblastoma multiforme (GBM) is one of the most malignant and aggressive brain
      tumors with great amount of hyaluronan (HA) secretion and CD44 overexpression (HA
      receptor). CD44 has been suggested as a cancer stem cells (CSCs) marker. However,
      several clinical studies have indicated that CD44low glioma cell exhibit CSCs
      traits. Additionally, our previous study indicated that more CD44 expression was
      associated with a better prognosis in GBM patients. To determine whether CD44 is
      an appropriate marker of glioma stem cells (GSCs), we manipulated CD44 expression
      using intrinsic (CD44 knockdown, CD44kd) and extrinsic (HA supplement, HA+)
      methods. Our results show that CD44kd suppressed cell proliferation by retarding
      cell cycle progression from G0/G1 to S phase. Furthermore, it caused GSCs traits,
      including lower expression of differentiation marker (glial fibrillary acidic
      protein, GFAP), a higher level of sphere formation and higher expression of stem
      cell markers (CD133, nestin and Oct4). The reduction of CD44 expression induced
      by HA+ was accompanied by an increase in GSCs properties. Interestingly, the
      presence of HA+ in glioma cells with GSC traits conversely facilitated
      differentiation. Our data indicated that the CD44 low-expressing cells exhibit
      more GSCs straits, suggesting that CD44 is not an appropriate marker for GSCs.
      Furthermore, the preferential expression of CD44 at the invasive rim in rat
      glioma specimen implies that CD44 may be more important for invasion and
      migration instead of GSCs marker in glioma.

PMID- 29218081
TI  - Tetramethylpyrazine phosphate and borneol combination therapy synergistically
      attenuated ischemia-reperfusion injury of the hypothalamus and striatum via
      regulation of apoptosis and autophagy in a rat model.
AB  - The combination of tetramethylpyrazine (TMP) and borneol (BO) has shown promise
      for treatment of cerebral ischemia in clinical and experimental studies. However,
      the mechanism for the synergistic effect of these compounds is unclear. In this
      study, global cerebral ischemia-reperfusion (GCIR) was induced in rats that were
      subsequently treated with tetramethylpyrazine phosphate (TMPP) (13.3 mg/kg), BO
      (0.16 g/kg), or the combination TMPP + BO. Neuronal ultrastructure and
      intracellular calcium [Ca2+]i levels were evaluated in hypothalamus and striatum.
      Neuron autophagy was evaluated by expression of LC3 II/I, ULK1, Beclin1, BNIP3,
      mTOR, and pAMPK. Neuron apoptosis was examined via apoptosis index (AI) and
      expression of p53, Bcl-2, Bax, and caspase-3. Both monotherapies significantly
      improved neuronal ultrastructure, reduced numbers of apoptotic neurons and AI,
      attenuated [Ca2+]i overload, increased expression of pAMPK, ULK1, and LC3 II/I,
      and markedly reduced expression of mTOR, p53, and caspase-3 in hypothalamus and
      striatum. In hypothalamus, TMPP increased Bcl-2 expression and decreased Bax
      expression. In striatum, TMPP and BO increased Beclin1 expression while TMPP
      increased Bcl-2 expression and decreased Bax expression. TMPP + BO combination
      therapy enhanced expression of LC3 II/I, pAMPK, mTOR, and ULK1 in hypothalamus,
      and pAMPK, mTOR, ULK1, Beclin1, and Bax in striatum compared to the
      monotherapies. Combination therapy synergistically modulated p53 and adjusted Bcl
      2 in striatum compared to TMPP and BO monotherapies, respectively. These results
      demonstrated a synergistic effect of TMPP + BO in protecting against hypothalamus
      and striatum in rats from ischemia-reperfusion injury and suggested that the
      mechanism involved shifting neurons from harmful apoptosis to protective
      autophagy and reducing neuronal [Ca2+]i.

PMID- 29218082
TI  - Functional characterization of CXCR4 in mediating the expression of protein C
      system in experimental ulcerative colitis.
AB  - The present study aimed to explore the role of CXCR4 and protein C system (PCS)
      in the experimental ulcerative colitis (UC). The expression of CXCR3, CCR10, and
      CXCR4 in dextran sulfate sodium (DSS)-induced colitis mouse model was measured by
      immunohistochemistry and western blot analysis. In vitro studies with
      microvascular endothelial cells (MVECs) were performed. The expression of
      endothelial protein C receptor (EPCR) and thrombomodulin (TM) were detected by RT
      PCR and western blot analysis. Activities of protein C (PC), protein S (PS),
      activated PC (APC) were evaluated in cells pre-treated with JNK inhibitor
      SP600125 and c-Jun silencing. DSS mice showed up-regulated expression of CXCR4,
      higher macroscopic score and histological score (P<0.05), as well as elevated
      levels of SDF-1alpha (P<0.05) compared with wild type, CXCR4-/-, or CXCR4-/- +DSS
      mice. In DSS mice, EPCR expression was down-regulated (P<0.05), accompanied by
      decreased activity of PC and PS (P<0.05 or P<0.01) with an up-regulated
      expression of pJNK MAPK and pc-Jun (P<0.05). Moreover, the macroscopic score and
      histological score index, SDF-1alpha levels, EPCR expression, PC activity, pJNK,
      and pc-Jun were reversed in CXCR4-/- +DSS mice (P<0.05). In vitro, SDF-1alpha
      induced inhibition of the PCS was blunted by SP600125 (P<0.05). Meanwhile, down
      regulation of c-Jun rescued the inhibition of PCS (P<0.05). MVECs with retrovirus
      mediated transfection of c-Jun demonstrated a strong trans-inactivation effect on
      the EPCR promoter (P<0.05). These findings suggest that CXCR4 is involved in UC
      pathogenesis and could be a promising therapeutic target for UC treatment.

PMID- 29218083
TI  - Overexpression and biological function of MEF2D in human pancreatic cancer.
AB  - To explore the expression, clinical significance, biological function, and
      potential mechanism of MEF2D in pancreatic cancer, the expression of MEF2D in
      human pancreatic cancer tissues and corresponding adjacent normal tissues was
      analyzed through immunohistochemical staining. The association between MEF2D
      expression, clinicopathological parameters, overall survival, and disease-free
      survival was evaluated. Human pancreatic cancer cell lines BxPC-1 and SW1990 were
      selected to investigate the effect of MEF2D knockdown on cell proliferation,
      migration, and invasion. Western blot analysis was used to assess the effect of
      MEF2D expression on the Akt/GSK pathway, as well as the protein expression of
      cyclin B1, cyclin D1, matrix metalloprotein (MMP)-2, and MMP-9. Our results
      revealed that the expression of MEF2D was increased in pancreatic cancer tissues
      compared to adjacent normal tissues and the increased expression of MEF2D was
      associated with tumor size, histological differentiation, and TNM stage of
      pancreatic cancer patients. Moreover, the expression of MEF2D was an independent
      prognostic indicator for pancreatic cancer patients. In addition, knockdown of
      MEF2D in pancreatic cancer cells inhibited cell proliferation, migration, and
      invasion by down-regulating the protein expression of cyclin B1, cyclin D1, MMP
      2, and MMP-9. Knockdown of MEF2D reduced the levels of phosphorylated Akt and GSK
      3beta. Our data indicated that MEF2D expression was increased in pancreatic
      cancer and was an independent molecular prognostic factor for pancreatic cancer
      patients. Furthermore, we showed that MEF2D controlled cell proliferation,
      migration, and invasion abilities in pancreatic cancer via the Akt/GSK-3beta
      signaling pathway.

PMID- 29218084
TI  - Regulation of osteogenic differentiation by DNA methylation of the dishevelled
      gene in bone marrow mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional
      differentiation potential, which can be used as seed cells to repair and
      reconstruct many types of tissues and organs following injury or disease.
      Osteogenic differentiation involves a variety of pathway and factors, including
      cytokines, growth factors, and hormones. In the present study, we investigated
      the potential role of Dishevelled in osteogenic differentiation of BMSCs in
      induction medium containing the methyltransferase inhibitor 5-aza-2'
      deoxycytidine. The expression of Dishevelled was analyzed using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) and a Western blot. The
      methylation degree of the CpG island in the promoter region of the Dishevelled
      gene was analyzed, and protein expression levels of Wnt, Glycogen synthase kinase
      3 (GSK3), axin, Dishevelled, and beta-catenin were increased after the addition
      of the methyltransferase inhibitor. The expression of Dishevelled increased in
      accordance with the differentiation of osteoblasts, and the degree of methylation
      of the promoter affected its expression level. In conclusion, regulating the
      methylation degree of the Dishevelled gene promoter region appears to influence
      the expression of Dishevelled and therefore the osteogenic differentiation of
      BMSCs.

PMID- 29218086
TI  - MicroRNA-520d-5p inhibits human glioma cell proliferation and induces cell cycle
      arrest by directly targeting PTTG1.
AB  - Glioma accounts for the majority of primary malignant brain tumors in adults and
      is highly aggressive. Although various therapeutic approaches have been applied,
      outcomes of glioma treatment remain poor. Acquiring a better understanding of the
      pathogenic mechanisms is essential to the design of effective therapeutic
      strategies. Previous studies have found that miR-520d-5p was negatively
      correlated with glioma grade, but its role and mechanism in glioma progression
      remain largely unknown. In the present study, we reported that miR-520d-5p
      directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned
      as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells
      and specimens were detected by Quantitative reverse transcription-PCR and
      Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma
      progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2
      deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase
      reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p.
      A xenograft model was used to study the effect of miR-520d-5p on tumor growth and
      angiogenesis. We found that miR-520d-5p expression was significantly decreased in
      glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant
      inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest
      in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d
      5p, and the protein expression of PTTG1 was markedly reduced after overexpression
      of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the
      inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies
      confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft
      tumors, which was accompanied by reduced expression of PTTG1. In conclusion,
      these results provide compelling evidence that miR-520d-5p functions as an anti
      onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its
      anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1
      expression. Therefore, we suggest that miR-520d-5p is a potential candidate for
      the prevention of glioblastoma.

PMID- 29218085
TI  - Identification and differential expression of microRNAs in 1, 25-dihydroxyvitamin
      D3-induced osteogenic differentiation of human adipose-derived mesenchymal stem
      cells.
AB  - The aim of this study was to identify specific microRNAs (miRNAs) and their
      regulatory roles in the process of 1, 25-dihydroxyvitamin D3-induced (VD3
      induced) osteogenic differentiation of human adipose-derived Mesenchymal stem
      cells (hAMSCs). The differentially expressed miRNAs in VD3-induced hAMSCs was
      examined. The putative target genes of these miRNAs were predicted. A total of 76
      conserved miRNAs, including 18 miRNAs were significantly up-regulated and 58
      miRNAs were significantly downregulated, and significantly differentially
      expressed between the two samples. The expression of 4 upregulated miRNAs (miR-1
      3p, miR-1247-5p, miR-217, and miRNA-483) and 5 downregulated miRNAs (miR-1284,
      miR-218, miR-582-3p, miR-187-3p, and miRNA-122-5p) were verified. The highly
      enriched GOs and KEGG pathway showed target genes of these miRNAs were
      significantly involved in multiple biological processes (signal transduction,
      cell differentiation, cell adhesion and cell proliferation), and several
      osteogenic pathways (MAPK signaling pathway, TGF-beta/BMP signaling pathway, and
      Wnt signaling pathway). Finally, TGF-beta/BMP signaling pathway was selected for
      target verification and function analysis. We observed that a number of osteo
      genes in the TGF-beta/BMP superfamily, such as BMPRI, BMPRII, TGFBRI, TGFBRII,
      BMP4, TGFbeta, Smad2, 3, 8, were predicted to be target gene of the
      differentially expressed miRNAs. Among them, TGFB, BMP4, BMPRI, and Smad8, which
      are positive regulators in osteoblast differentiation, were confirmed to be
      significantly up-regulated in VD3-induced cells by qRT-PCR; while Smad6 and
      activinRI, which are negative regulators of the TGF-beta/BMP superfamily, were
      shown to be significantly down-regulated. These results will help to understand
      the role of miRNA in the regulation of the osteogenic differentiation of hAMSCs.

PMID- 29218087
TI  - The cytoskeleton protein beta-actin may mediate T cell apoptosis during acute
      rejection reaction after liver transplantation in a rat model.
AB  - Cytoskeletal proteins and associated regulatory proteins are essential for
      maintaining cell structure and growth. beta-actin is a major component of the
      cytoskeleton, and beta-actin remodeling is involved in lymphocyte migration,
      infiltration and apoptosis. However, little is known about whether changes in
      beta-actin expression affect lymphocyte cell fate, particularly during acute
      rejection after liver transplantation in a rat model. In our studies, grafts were
      harvested on days 5, 7 or 9 after xenogeneic rat liver transplantation. The acute
      rejection grade was histopathologically evaluated. Recipient-derived CD8+ T
      lymphocytes gradually infiltrated into liver allografts in cases of severe acute
      rejection. The apoptotic rate of CD8+ T lymphocytes peaked on day 7 and then
      decreased. Moreover, changes in beta-actin expression were consistent with the
      apoptotic rate of CD8+ T lymphocytes in both allografts and peripheral blood
      based on western blotting and immunohistochemistry results. Additionally,
      jasplakinolide (an actin-stabilizing drug) evoked CD8+ T lymphocyte apoptosis. In
      conclusion, our study is the first to describe the fluctuating expression levels
      and dynamics of the cytoskeletal protein beta-actin and its potential roles in
      the pathogenesis of acute rejection following rat liver transplantion. Our
      results enhance the understanding of the roles of CD8+ T lymphocytes during acute
      rejection and suggest that beta-actin regulation leads to apoptosis.

PMID- 29218088
TI  - Effect of astragaloside IV on diabetic gastric mucosa in vivo and in vitro.
AB  - This study evaluated the effects of AS-IV on high glucose induced-gastric mucosal
      lesions compared to the effects of the Bu-zhong-yi-qi pill and the Xiaoke pill,
      which are already in clinical use. STZ-induced diabetic SD rats were treated with
      drugs for 12 weeks. Diabetes serum (DS) was used to mimic high glucose conditions
      in GES-1 cells in vitro at different concentrations and time points. The drugs
      were set at three concentration gradients for 24, 48 and 72 h before being added
      to DS-induced GES-1 cells. The proliferation activity and inhibition ratio of
      cells were measured by the CCK-8 assay. Gastric tissues were examined by H&E
      staining. Cell morphology was observed by inverted phase contrast microscopy.
      Apoptosis of cells was detected by annexin V-FITC/PI. In addition, expression
      levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and
      mucin1 (MUC1) were measured by Western blots. We found that the drugs
      significantly alleviated the pathological damage in STZ-induced gastric mucosal
      lesions. DS inhibited the viability of the cells in a dose and time-dependent
      manner, while pretreatment with drugs reversed these effects. Pretreatment with
      drugs also ameliorated the changes in cell morphology and inhibited cell
      apoptosis. Furthermore, the drugs decreased the expression levels of iNOS, COX-2
      and MUC1. AS-IV showed the most beneficial effect compared with buzhong and
      xiaoke. These results suggest that AS-IV had a significant effect on high glucose
      induce gastric mucosal lesions compares with buzhong and xiaoke. We speculate
      that this is in part through restoring the balance of iNOS, COX-2 and MUC1
      expressions. Thus, AS-IV may be a potential antioxidant drug for treating
      diabetic gastropathy.

PMID- 29218089
TI  - The role of sildenafil in the development of transplant arteriosclerosis in rat
      aortic grafts.
AB  - Chronic rejection (CR), which is characterized histologically by progressive
      graft arteriosclerosis, remains a significant barrier to the long-term survival
      of a graft. Sildenafil has been shown to protect vascular endothelial cells. In
      this study, we found that sildenafil significantly reduces the thickness of
      transplant vascular intima in a rat aortic transplant model. Moreover, sildenafil
      dramatically decreased the expression of transforming growth factor-beta1 (TGF
      beta1), vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin
      (alpha-SMA) in the grafted aortas and increased the concentrations of cyclic
      guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) in
      serum. Furthermore, the ratio of regulatory T (Treg) cells and the expression of
      FoxP3 were increased, and the ratio of Th17 cells was decreased in the sildenafil
      treated group. These results demonstrate that sildenafil enhances nitric oxide
      (NO) signaling by increasing the availability of cGMP, leading to an increase in
      the ratio of Treg/Th17 cells to attenuate transplant arteriosclerosis in a rat
      aortic transplant model.

PMID- 29218090
TI  - Mir-24 regulates hepatocyte apoptosis via BIM during acute liver failure.
AB  - Acuteliver failure (ALF) has a high mortality rate and is characterized by
      massive hepatocyte destruction. Although microRNAs (miRNAs) play an important
      role in manyliver diseases, the role of miRNAs in ALF development is unknown. In
      this study, the murine ALF model was induced by intraperitoneal injection of D
      galactosamine/lipopolysaccharide (D-GalN/LPS). Compared with saline-treated mice,
      miR-24 was distinctly down-regulated post D-GalN/LPS challenge in vivo and D
      galactosamine/tumor necrosis factor (D-GalN/TNF) challenge in vitro, which was
      confirmed by quantitative real-time polymerase chain reaction. Meanwhile, the
      mRNA and protein levels of the BH3-only-domain-containing protein BIM were
      upregulated after challenge both in vivo and in vitro. Previous studies have
      demonstrated that hepatocyte apoptosis is a distinguishing feature of D-GalN/LPS
      associated liver failure. In this study, D-GalN/LPS-challenged mice showed higher
      alanine aminotransferase and aspartate aminotransferase levels, more severe liver
      damage, increased numbers of apoptotic hepatocytes and higher levels of caspase-3
      compared with saline-treated mice. In D-GalN/TNF-treated BNLCL2 cells, miR-24
      overexpression attenuated apoptosis.Furthermore, miR-24 overexpression reduced
      BIM mRNA and protein levels in vitro. Taken together, these findings demonstrate
      that miR-24 regulates hepatocyte apoptosis via BIM during ALF development,
      suggesting that miR-24 is a novel onco-miRNA that may provide potential
      therapeutic targets for ALF.

PMID- 29218091
TI  - Angiogenic and wound healing potency of fermented virgin coconut oil: in vitro
      and in vivo studies.
AB  - OBJECTIVE: The process of wound healing involves activation of keratinocytes,
      fibroblasts, endothelial cells, etc. Angiogenesis is crucial during the process
      of wound healing. Virgin coconut oil is widely utilized in South Asia for various
      purposes including food, medicinal and industrial applications. This study aimed
      to evaluate the potency of fermented virgin coconut oil (FVCO) in angiogenesis
      and wound healing via both in vitro and in vivo assays. METHODS: Human umbilical
      vein endothelial (HUVEC), fibroblast (CCD-18) and retinal ganglion (RGC-5) cells
      were cultured in medium containing different concentrations of FVCO. The
      proliferation, migration and morphological changes of cells were determined. The
      angiogenic effect of FVCO was evaluated by rat aortic assay. The therapeutic
      effect of FVCO on wound healing was further assessed in a wound excision model in
      Sprague Dawley rats. The expression of phospho-VEGFR2 (vascular endothelial
      growth factor receptor 2) in HUVECs was detected by Western blot. RESULTS: FVCO
      (6 and 12 ug/mL) significantly improved the proliferation of HUVEC, CCD-18 and
      RGC-5 cells (P < 0.05 or 0.01). FVCO (25 ug/mL) markedly increased the migration
      ability of CCD-18 and RGC-5 cells (P < 0.05). FVCO did not affect cell morphology
      as indicated by fluorescein diacetate (FDA), rhodamine 123 and Hoechst staining.
      FVCO (25, 50 and 100 ug/mL) significantly stimulated the ex vivo blood vessel
      formation as compared with negative control (P < 0.05). Rats in FVCO group had
      significantly smaller wound size, higher wound healing percentage, and shorter
      wound closure time when compared with control group since day 8 (P < 0.05),
      suggesting that oral FVCO administration notably promoted the wound healing
      process. FVCO treatment (6 and 12 ug/mL) significantly enhanced the phospho
      VEGFR2 expression in HUVECs (P = 0.006 and 0.000, respectively). CONCLUSION: Our
      study confirms a high angiogenic and wound healing potency of FVCO that might be
      mediated by the regulation of VEGF signing pathway.

PMID- 29218092
TI  - Hsp90 inhibitor sensitizes TRAIL-mediated apoptosis via chop-dependent DR5
      upregulation in colon cancer cells.
AB  - Heat shock protein 90 (Hsp90), a molecular chaperone, is involved in a variety of
      physiological and pathological processes. Targeting Hsp90 by small molecules has
      been developed as an attractive strategy of anticancer therapy. In this study, we
      investigated the mechanism of Hsp90 inhibitor suppresses CRC growth and
      potentiates effects of other chemotherapeutic drugs. We found that Hsp90
      inhibitor induces chop-dependent DR5 upregulation regardless of p53 status.
      Furthermore, DR5 is required for Hsp90 inhibitor-induced apoptosis. Hsp90
      inhibitor also synergized with TRAIL to induce marked apoptosis via DR5 in CRC.
      Overall, our results illustrate DR5 play a key role in mediating the anticancer
      effects of Hsp90 inhibitor in CRC and suggest that DR5 expression can be used as
      an indicator of Hsp90 inhibitor sensitivity, which has important implications for
      it clinical applications.

PMID- 29218093
TI  - P2X7 receptor regulates sympathoexcitatory response in myocardial infarction rats
      via NF-kappaB and MAPK pathways.
AB  - Previous studies have provided evidence for the regulatory effect of P2X7
      receptor (P2X7R) on cardiovascular activities. Our study focused on exploring the
      function and fundamental mechanism of microglial P2X7R in controlling
      sympathoexcitatory response using rats with acute myocardial infarction (AMI).
      Coronary artery ligation was used in rats to cause AMI. And before that, rats
      were administrated with P2X7R siRNA that targeted P2X7R mRNA into paraventricular
      nucleus (PVN) or BBG (Brilliant Blue G, a P2X7 receptor antagonist). Increased
      expression levels of P2X7R and adenosine triphosphate (ATP) were observed in the
      hypothalamic PVN of AMI rats. Moreover, the knockdown of P2X7R expression by P2X7
      siRNA or suppression of P2X7 receptor by BBG attenuated the elevation of both
      vasopressin and oxytocin levels in the PVNs of AMI rats. There was also a
      decrease in renal sympathetic nerve activity (RSNA) by P2X7-siRNA and BBG.
      Besides, inflammation was alleviated by P2X7-siRNA and BBG through suppressing
      pro-inflammatory cytokines IL-1beta and IL-6 in PVN of AMI rats. Furthermore,
      blockade of P2X7R moderated the process of cardiac remodeling. This was achieved
      due to the regulatory effect of P2X7R on sympathoexcitatory response by
      influencing NF-kappaB and mitogen-activated protein kinase (MAPK) signaling.
      These findings suggest that P2X7R can act as a new regulator of
      sympathoexcitatory response via NF-kappaB and MAPK signaling pathways in AMI
      rats.

PMID- 29218094
TI  - MiR-351 negatively regulates osteoblast differentiation of MSCs induced by (+)
      cholesten-3-one through targeting VDR.
AB  - Our previous reports indicated that (+)-cholesten-3-one induces osteogenic
      differentiation of bone marrow mesenchymal stem cells (MSCs) by activating
      vitamin D receptor (VDR). However, whether and how miRNAs modulate osteogenic
      differentiation induced by (+)-cholesten-3-one have not been explored. In this
      study, miRNA array profiling and further validation by quantitative real-time PCR
      revealed that miR-351 was downregulated during (+)-cholesten-3-one-induced
      osteogenic differentiation of MSCs. Overexpression of miR-351 by miR-351
      precursor transfection markedly inhibited the expression of osteoblast-specific
      genes, such as alkaline phosphatase (ALP), collagen type II, osteopontin (OPN),
      and runt-related transcription factor 2 (RUNX2), which consequently decreased a
      number of calcium mineralized nodules. Inhibition of miR-351 function by anti-miR
      351 promoted expression of osteoblast-specific genes. Our results suggest that
      miR-351 is a negative regulator of osteoblast differentiation of MSCs induced by
      (+)-cholesten-3-one. Target prediction analysis tools and experimental validation
      by luciferase 3'UTR reporter assay identified VDR as a direct target of miR-351.
      miR-351 inhibited the expression of the VDR, which played a critical role in the
      control of osteogenic differentiation of MSCs. Importantly, overexpression of VDR
      significantly abolished the inhibitory effect of miR-351 on (+)-cholesten-3-one
      induced osteogenic differentiation. Taken together, our results demonstrate that
      miR-351 negatively regulates osteoblast differentiation of MSCs induced by (+)
      cholesten-3-one through targeting VDR. These findings provid evidence that miR
      351 can bea possible therapeutic target for bone repair and regeneration.

PMID- 29218095
TI  - Effect of repeated neonatal sevoflurane exposure on the learning, memory and
      synaptic plasticity at juvenile and adult age.
AB  - Currently sevoflurane is the volatile anesthetic most wildly used in pediatric
      surgery. Whether neonatal exposure to sevoflurane brings about a long-lasting
      adverse impact even at juvenile and adult age, attracts extensive concerns.
      However, to date the consensus has not been reached and how exposure to
      sevoflurane in early life affects long-term ability of learning and memory is not
      fully elucidated. To obtain further insight into this issue, 32 neonatal SD rats
      were assigned into control group (group C, n=16) and sevoflurane group (group
      SEV, n=16). At postnatal day 7 (P7), 14 (P14) and 21 (P21) rats pups in group SEV
      received repeated exposure to 2.6% sevoflurane for 2 h. At juvenile and adult
      age, Morris water maze (MWM) was used to determine the spatial memory
      performance. Subsequently long-term and short-term synaptic plasticity in
      hippocampal CA1 region were investigated by in vivo electrophysiological method.
      Our behavioral data revealed that repeated exposure to 2.6% sevoflurane in early
      life did not result in marked behavioral abnormalities. However, in
      electrophysiological experiment, long-term potentiation (LTP) in hippocampal
      neurons of animals neonatally exposed to sevoflurane was significantly inhibited
      as compared to animals in group C at both juvenile and adult age. Pair-pulse
      facilitation (PPF) ratio in group SEV at juvenile and adult age was augmented to
      varying extent. These effects were most noticeable at juvenile stage with
      tendency of alleviation during adulthood. The present study provides an
      alternative explanation for the mechanism underlying developmental neurotoxicity
      of sevoflurane, which may ameliorate future preventive and therapeutic
      strategies.

PMID- 29218096
TI  - MiR-106a promotes tumor growth, migration, and invasion by targeting BCL2L11 in
      human endometrial adenocarcinoma.
AB  - Growing evidence indicates that miR-106a is involved in tumor growth and
      metastasis of cancers, but the participation of miR-106a in endometrial
      adenocarcinoma (EC) is not clear. BCL2L11 is a member of the BCL-2 family and is
      located in the outer membrane of mitochondria, where this protein acts as a key
      regulator of excitotoxic apoptosis, apoptosis-inducing factor translocation, and
      mitochondrial depolarization. To identify a novel therapeutic target in EC, we
      studied the roles of miR-106a in the proliferation, apoptosis, and metastasis of
      EC. The expression levels of miR-106a were measured in tumor tissues of EC by
      quantitative real-time PCR, and lentiviral transduction was used to verify the
      function of miR-106a by silencing. Subcutaneous injection of EC cell lines into
      athymic mice was used to research EC tumor formation. Bioinformatics tools and a
      luciferase assay were applied to assess the relation between miR-106a and its
      target. The protein level of the miR-106a target was measured by western
      blotting. MiR-106a expression was higher in EC tissues compared with their
      healthy counterparts. Inhibition of expression of miR-106a reduced EC cell
      migration and invasion in vitro as well as in vivo tumor growth. BCL2L11 mRNA
      contains a binding site for miR-106a in the 3'untranslated region. BCL2L11 was
      found to be one of miR-106a targets. Altogether, our data suggest that miR-106a
      inhibits proliferation and invasiveness and induces cell cycle arrest and
      apoptosis in EC cells by targeting BCL2L11, and therefore miR-106a may serve as a
      prognostic marker of EC.

PMID- 29218097
TI  - Histone deacetylase inhibitor NaBut suppresses cell proliferation and induces
      apoptosis by targeting p21 in multiple myeloma.
AB  - Multiple myeloma (MM) is an extremely serious hematological malignancy that
      remains incurable due to chemotherapy resistance. Epigenetic regulation is
      closely associated with progression of MM. Histone deacetylase inhibitor NaBut
      functions in various physiologic processes, including inflammation and
      differentiation. Its' possible roles in MM progression have not been explored. In
      this report, NaBut decreased survival of several human MM cell lines in a dose-
      and time-dependent manner. NaBut could also lead to cell cycle arrest at the G2/M
      phase in a dose-dependent manner. NaBut inhibited bortezomib-resistant cell
      proliferation in dose- and time-dependent manners, and NaBut was likely to induce
      partly bortezomib-resistant MM cell death. Moreover, NaBut induced MM cell
      apoptosis via transcriptional activation of p21. Overall, our results implicate
      NaBut as a potential therapeutic drug for MM.

PMID- 29218098
TI  - Overexpression of microRNA-145 protects against rat myocardial infarction through
      targeting PDCD4.
AB  - Myocardial infarction (MI) is a common cardiovascular disease with high
      mortality. The aim of the present study was to determine the biological role of
      miR-145 in MI rats and hypoxia-injured cardiomyocytes and to elucidate the
      potential mechanism. MI rats were induced by left anterior descending artery
      (LAD) ligation. qRT-PCR and western blot analysis were performed to determine the
      mRNA and protein levels, respectively. Compared with sham group, miR-145 levels
      in MI group were significantly decreased. We observed that lentivirus-mediated
      overexpression of miR-145 significantly improves cardiac function, reduces
      infarcted tissue size and prevents post-infarction induced apoptosis in rats
      after MI. Furthermore, PDCD4 was identified as a novel target of miR-145 in
      cardiomyocytes, and overexpression of PDCD4 could remarkably restore the miR-145
      inhibited cardiomyocytes apoptosis and mitochondrial dysfunction after hypoxia
      injury. Therefore, our study indicated that miR-145/PDCD4 axis might be potential
      therapeutic targets for the treatment of MI, and its cardioprotective effect may
      be attributed to a reduction of mitochondria-mediated apoptosis.

PMID- 29218099
TI  - Long non-coding RNA HOTAIR enhances angiogenesis by induction of VEGFA expression
      in glioma cells and transmission to endothelial cells via glioma cell derived
      extracellular vesicles.
AB  - Gliomas are one the most prevalent malignant carcinomas of the central nervous
      system, and angiogenesis plays a critical role in the progression of these blood
      vessel-rich tumors. HOTAIR, a long non-coding RNA (lncRNA), acts as an oncogene
      in gliomas; however, its role in glioma angiogenesis remains unclear. In the
      present study, we identified a pro-angiogenic activity of HOTAIR. Silencing
      HOTAIR inhibited glioma-induced endothelial cell proliferation, migration, and
      tube formation. Further studies showed that vascular endothelial growth factor A
      (VEGFA) was involved in the HOTAIR-induced glioma angiogenesis. Our study also
      showed that HOTAIR was present in the glioma cell culture supernatant and was
      protected by membranes, suggesting that HOTAIR may affect glioma angiogenesis not
      only via regulation of VEGFA expression in the glioma cells, but also by
      transmission into endothelial cells via glioma cell-derived extracellular
      vesicles.

PMID- 29218100
TI  - Staphylococcus aureus peptidoglycan promotes osteoclastogenesis via TLR2-mediated
      activation of the NF-kappaB/NFATc1 signaling pathway.
AB  - Staphylococcus aureus (S. aureus) peptidoglycan (PGN-sa), the major cell wall
      component of S. aureus, has been demonstrated to be an important virulence factor
      in the pathogenesis of S. aureus-induced osteomyelitis. However, the exact role
      of PGN-sa in osteoclastogenesis during S. aureus-induced osteomyelitis and its
      underlying molecular mechanisms remain unclear. In this study, we found that PGN
      sa promoted receptor activator of nuclear factor-kappaB (NF-kappaB) ligand
      (RANKL)-induced osteoclast formation. Quantitative real-time polymerase chain
      reaction results showed that the mRNA expression of osteoclast-specific marker
      genes, including tartrate-resistant acid phosphatase, cathepsin K, matrix
      metalloproteinase-9, and calcitonin receptor was upregulated by PGN-sa treatment.
      The results of enzyme linked immunosorbent assay showed that PGN-sa promoted the
      production of proinflammatory cytokines in mouse bone marrow macrophages (mBMMs)
      treated with RANKL. PGN-sa enhanced RANKL-stimulated protein expression of Toll
      like receptor 2 (TLR2), p-IkappaBalpha, and nuclear factor of activated T-cells,
      cytoplasmic 1 (NFATc1). Luciferase reporter assay showed that PGN-sa increased
      the transcriptional activity of TLR2 and NF-kappaB in mBMMs treated with RANKL.
      In addition, we found that downregulation of TLR2 attenuated the effect of PGA-sa
      on RANKL-induced osteoclastogenesis and activation of the NF-kappaB/NFATc1
      signaling pathway. Taken together, this study revealed that PGN-sa promotes
      osteoclast formation via TLR2-mediated activation of the NF-kappaB/NFATc1
      signaling pathway, revealing a potential effect of PGN-sa on osteomyelitis. These
      findings provide new insights into the pathogenic role of PGN-sa in S. aureus
      induced osteomyelitis and may help to develop new therapeutic strategies for
      osteomyelitis.

PMID- 29218101
TI  - Delta/notch-like epidermal growth factor-related receptor (DNER) orchestrates
      stemness and cancer progression in prostate cancer.
AB  - DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a
      neuron-specific transmembrane protein carrying extracellular EGF-like repeats.
      The function of DNER in prostate cancer has not been evaluated. Here, we showed
      that the upregulation of DNER is observed in various cancers, including prostate
      cancer. Knockdown of DNER in PC-3 cells inhibited cell proliferation, migration
      and invasion as well as tumorigenesis in PC-3 xenografts. DNER knockdown
      specifically inhibited cell growth in spheroids. RT-PCR and western blot analysis
      were performed, and CD44, HES1 and GLI1 expression was significantly decreased in
      DNER knockdown cells. Thus, DNER promotes prostate cancer progression and the
      growth of PC-3 cells by modulating the primary genes of cancer stem cells.

PMID- 29218102
TI  - Dexmedetomidine alleviates LPS-induced septic cardiomyopathy via the cholinergic
      anti-inflammatory pathway in mice.
AB  - This study was conducted to investigate the role of the cholinergic anti
      inflammatory pathway in LPS-induced septic cardiomyopathy in mice. C57BL/6 mice
      were used to construct septic cardiomyopathy models. The optimal duration of
      lipopolysaccharide (LPS) treatment was determined by HE staining and TUNEL assay.
      Blank controls were intraperitoneally injected with saline and models were
      injected with LPS (10 mg/kg) (LPS), alpha-bungarotoxin (BT-LPS), BT and
      dexmedetomidine (BT-DEX-LPS). The pathological examinations were performed on HE-
      stained myocardium tissues, apoptosis was determined using TUNEL assay, mRNA
      expression of NF-kappaB p65, Caspase-3, Caspase-8, Bcl-2, Bax, p53 and alpha7nACh
      was quantified using qRT-PCR, protein levels of IL-6, IL-1beta, TNF-alpha and
      phosphorylated STAT3 (p-STAT3) were analyzed using Western blot analysis. HE
      staining and TUNEL assays showed that the optimal LPS treatment time for septic
      cardiomyopathy induction was 16 h. Compared with the blank control, mice in LPS
      group had significantly higher apoptosis, while DEX and BT reduced apoptosis when
      they were used separately and increased apoptosis when they were used jointly. In
      the LPS-treated mice, the levels of NF-kappab p65, Caspase-3, Caspase-8, Bax,
      p53, IL-6, IL-1beta, TNF-alpha and p-STAT3 were significantly increased, while
      alpha7nAChR level was decreased significantly (P < 0.01); DEX alone had no impact
      on the expression of these proteins but significantly up-regulated the expression
      of these genes except alpha7nAChR when used jointly with BT (P < 0.01). It is
      clear that DEX can alleviate heart injury, while alpha7nAChR-specific blocker BT
      is antagonistic against the anti-inflammatory effect of DEX on sepsis in mice.

PMID- 29218103
TI  - MicroRNA-429 sensitizes pancreatic cancer cells to gemcitabine through regulation
      of PDCD4.
AB  - One of the features for pancreatic cancer is that it is often resistant to
      chemotherapy treatment, which is one of the major hindrances in the treatment of
      this malignancy. Previous studies indicated that the microRNAs (miRNAs) could
      mediate resistance of tumor cells to chemotherapy drug in the cancer progression.
      In the present study, we are aimed to examine whether microRNA-429 was involved
      in mediating the chemo-resistance of pancreatic cancer cells to gemcitabine.
      Firstly, a gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) derived
      from cell line (SW1990) was constructed and found to possess a decreased
      expression of miR-429 when it is compared to the original cell line. Ectopic
      expression of miR-429 in SW1990/GZ increased the cellular sensibility to the
      treatment of gemcitabine, which is coincided with increased expression of PDCD4.
      As a tumor suppressor, we found that PDCD4 knockdown in SW1990/GZ cells increased
      its own chemo-resistance to GZ, which indicates PDCD4 also play a regulative role
      on the GZ-resistance in the pancreatic cancer. To further confirm the function of
      miR-429 and PDCD4 in gemcitabine-resistant pancreatic cancer, a xenograft nude
      mouse model was utilized to examine whether miR-429 can restore treatment
      response of gemcitabine in gemcitabine-resistant xenografts, while protein levels
      of PDCD4 were up-regulated. Together with those results, these findings
      collectively provided that miR-429 could enhancer GZ sensitivity via regulation
      of PDCD4 expression in pancreatic cancer cells, which may offer a novel
      therapeutic target for the chemotherapy resistance in pancreatic cancer.

PMID- 29218104
TI  - Aspirin inhibits the proliferation of synovium-derived mesenchymal stem cells by
      arresting the cell cycle in the G0/G1 phase.
AB  - Mesenchymal stem cells (MSCs) provide promising applications for clinical
      treatments. However, patients often take medications that affect the viability of
      transplanted MSCs. The aim of this study was to assess the effects and underlying
      mechanism of action of aspirin on the proliferation of MSCs. We showed that
      aspirin inhibited the growth of MSCs in a concentration- and time-dependent
      manner. Analysis of cell-cycle distributions showed significantly increased cell
      populations in the G0/G1 phase and decreased cell populations in the S phase and
      G2/M phase with increasing concentrations of aspirin. We further analyzed the
      expression of cyclins and found that the level of cyclin D1 was significantly
      reduced after aspirin treatment, while there was no obvious effect on the levels
      of cyclin A2 and cyclin E1. Because we showed that the expression of miRNA145 was
      significantly increased after aspirin treatment, we further transfected MSCs with
      an miRNA145 mimic or miRNA145 inhibitor. Transfection with the miRNA145 mimic
      resulted in decreased expression of cyclin D1, while transfection with miRNA145
      inhibitor resulted in increased expression of cyclin D1. Transfection with
      miRNA145 inhibitor abolished the downregulation of cyclin D induced by aspirin.
      The results suggested that aspirin inhibited the proliferation of MSCs and caused
      cell-cycle arrest in the G0/G1 phase through downregulation of cyclin D1, which
      could be related to the increased expression of miRNA145.

PMID- 29218105
TI  - Systemic inflammation is associated with myocardial fibrosis, diastolic
      dysfunction, and cardiac hypertrophy in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Regional or diffuse fibrosis is an early feature of hypertrophic
      cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have
      documented low-grade inflammation in HCM. The aim of this study was to examine
      the relationships between circulating inflammatory markers and myocardial
      fibrosis, systolic and diastolic dysfunction, and the degree of cardiac
      hypertrophy in HCM patients. METHODS AND RESULTS: Fifty HCM patients were
      recruited while 20 healthy subjects served as the control group. Seventeen
      inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic
      resonance imaging and echocardiography were used to assess cardiac phenotypes.
      Tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and serum amyloid P (SAP)
      were significantly increased in HCM patients compared to controls. IL-6, IL-4,
      and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis
      while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse
      fibrosis. Fractalkine and interferon-gamma were associated with left ventricular
      wall thickness. The above associations remained significant in a linear
      regression model including age, gender, body mass index and family history. TNF
      alpha, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic
      dysfunction. White blood cells were also increased in HCM patients and correlated
      with diffuse fibrosis and diastolic dysfunction. However the associations between
      parameters of systemic inflammation and diastolic dysfunction were weakened in
      the linear regression analysis. CONCLUSIONS: Systemic inflammation is associated
      with parameters of the disease severity of HCM patients, particularly regional
      and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in
      HCM patients.

PMID- 29218106
TI  - Extracorporeal shock wave therapy effectively protects brain against chronic
      cerebral hypo-perfusion-induced neuropathological changes.
AB  - This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy
      could protect mouse brain from chronic cerebral hypoperfusion (CHP)-induced
      neuropathological changes in a bilateral carotid arterial stenosis (CAS) model.
      Adult-male C57BL/6 (B6) mice (n=36) were randomized into group 1 (sham-control),
      group 2 (CHP) and group 3 [CHP+ECSW (100 impulses at 0.15 mJ/mm2) on day 5, 10
      and 15 after CHP induction]. By day 60 after CHP induction, the white matter
      lesion, protein expressions of inflammatory (TNF-alpha/NF-kappaB/iNOS), oxidative
      stress (NOX-1/NOX-2/NOX-4/nitrotyrosine), angiogenesis (eNOS/CD31), apoptotic
      (Bax/caspase-3/PARP), fibrotic (Smad3/TGF-beta) and mitochondrial-damaged
      (cytosolic cytochrome-C) biomarkers were significantly higher in group 2 than in
      groups 1 and 3, and significantly higher in group 3 than in group 1, whereas the
      protein expressions of anti-apoptotic (Bcl-2), anti-fibrotic (BMP-2/Smad1/5), and
      mitochondrial-integrity (mitochondrial cytochrome-C) biomarkers showed an
      opposite pattern to inflammation among the three groups (all P<0.0001). The
      cellular expressions of inflammatory (Iba-1/GFAP/CD14, F4/80), apoptotic (TUNEL
      assay) and brain-damaged (gamma-H2AX/AQP4) biomarkers showed an identical pattern
      to inflammation, whereas the cellular expressions of endothelial-cell (CD31/vWF),
      neuron/energy-integrity (NeuN/PGC-1alpha) and small-vessel density exhibited an
      opposite pattern to inflammation among the three groups (all P<0.0001). Cellular
      angiogenesis (VEGF/SDF-1alpha) significantly and progressively increased from
      groups 1 to 3 (all P<0.0001). In conclusion, ECSW therapy enhanced angiogenesis,
      inhibited molecular-cellular perturbations, and protected the white matter and
      neuron from CHP damage.

PMID- 29218107
TI  - Scutellarin suppresses human colorectal cancer metastasis and angiogenesis by
      targeting ephrinb2.
AB  - Tumor induced angiogenesis is an attractive target for anti-cancer drug
      treatment. Scutellarin, which is a native compound derived from scutellaria
      altissima leaves, has already been proved to possess anti-tumor activities.
      Nevertheless, their effects in colorectal cancer metastasis and angiogenesis have
      not been evaluated. In order to reveal the anti-angiogenic and anti-metastasis
      capacity of scutellarin, wound healing and Transwell chamber inserts invasion
      were done in colorectal cancer cells, and cell proliferation as wells colony
      formation were conducted to identify the proliferation inhibition of colorectal
      cancer in vitro. The growth inhibition of scutellarin was further definite by a
      mouse colorectal xenograft model in vivo. Herein, we demonstrated scutellarin
      suppressed colorectal cancer cell viability and colony formation in vitro, and
      remarkably reduced tumor growth in vivo mouse xenografts. Additionally,
      scutellarin restrained colorectal cancer cells-induced angiogenesis, inhibited
      human umbilical vascular endothelial cells (HUVECs) migration, tube formation of
      HUVECs, and micro-vessel formation in chick embnyo chorioallantoic menbreme (CAM)
      assay. Altogether, our results exhibited the evidence that scutellarin inhibit
      colorectal cancer angiogenesis and metastasis via targeting ephrinb2 signaling,
      with the potential of an anti-tumor agent for cancer treatment.

PMID- 29218108
TI  - The synergistic effect of esophageal squamous cell carcinoma KYSE150 cells and M2
      macrophages on lymphatic endothelial cells.
AB  - Objective: This study aimed to investigate whether tumor-associated macrophages
      (TAMs) and esophageal squamous cell carcinoma (ESCC) cells could synergistically
      influence the generation of lymphatic vessels via the VEGF-C/VEGFR-3 signaling
      pathway and to address its mechanism. Methods: M2 macrophages were sorted with
      immunomagnetic beads and induced in vitro. VEGF-C siRNA plasmids were constructed
      and transfected into M2 macrophages and the ESCC cell line KYSE150. Different
      conditioned culture media before and after transfection were collected and
      classified into different groups for culturing ESCC-associated lymphatic
      endothelial cells (ESCC-LECs). Using the CCK-8 assay, Transwell cell migration
      assay and Matrigel three-dimensional culture, the proliferation, migration and
      ring forming abilities of ESCC-LECs before and after transfection were compared,
      respectively. With ELISA, western blot and q(RT)-PCR, VEGF-C concentrations in
      conditioned culture media and the protein and mRNA expression levels of VEGFR-3
      in LECs before and after transfection were compared, respectively. Results:
      Before transfection, ESCC-LECs in the group with mixed culture medium had
      stronger proliferation, migration and ring forming abilities than the other
      groups. The VEGF-C concentration and VEGFR-3 protein and mRNA expression levels
      were higher in the mixed culture medium group than in the other groups. After
      transfection, all indices were the lowest in the mixed culture medium group.
      Conclusions: M2 macrophages can enhance the proliferation, migration and ring
      forming abilities of ESCC-LECs. ESCC cells and M2 macrophages have synergistic
      effects on the proliferation, migration and ring forming abilities of ESCC-LECs.
      VEGF-C siRNA can inhibit the proliferation, migration and ring forming abilities
      of ESCC-LECs by silencing the expression of VEGF-C and its receptor VEGFR-3 in
      KYSE150 cells and M2 macrophages.

PMID- 29218109
TI  - Rational lung tissue and animal models for rapid breath tests to determine
      pneumonia and pathogens.
AB  - OBJECTIVE: This study works to develop novel models that may be adopted for
      earlier non-invasive breathomics tests to determine pneumonia pathogens. METHODS:
      Two types of pneumonia models were created, both in vitro and in vivo.
      Paraneoplasm lung tissue and specific pathogen-free (SPF) rabbits were adopted
      and separately challenged with sterile saline solution control or three
      pathogens: Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.
      After inoculation, headspace air or exhaled air were absorbed by solid phase
      micro-extraction (SPME) fibers and subsequently analyzed with gas chromatograph
      Mass Spectrometer (GCMS). RESULTS: Pneumonia and pathogen-specific discriminating
      VOC patterns (1H-Pyrrole-3-carbonitrile, Diethyl phthalate, Cedrol, Decanoic
      acid, Cyclohexane, Diisooctyl phthalate) were determined. CONCLUSION: Our study
      successfully generated nosocomial pneumonia models for pneumonia diagnosis and
      pathogen-discriminating breath tests. The tests may allow for earlier pneumonia
      and pathogen diagnoses, and may transfer empirical therapy to targeted therapy
      earlier, thus improving clinical outcomes.

PMID- 29218110
TI  - Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine
      autoimmune diabetes.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive
      injury of islet cells mediated by T lymphocytes (T cells). Our previous studies
      have shown that only cathepsin G (CatG), not other proteases, is involved in the
      antigen presentation of proinsulin, and if the presentation is inhibited, the
      activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients,
      and CatG-specific inhibitor reduces the activation of CD4+ cells induced by
      proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an
      important role in the activation of CD4+ T cells in T1DM. To this end, mouse
      studies were conducted to demonstrate that CatG impacts the activation of CD4+ T
      cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation
      of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was
      investigated in NOD mice on the activation of CD4+ T cells, islet beta cell
      function, islet inflammation and beta-cell apoptosis. Furthermore, NOD mice were
      injected with CatG siRNA in early stage to observe the effect of CatG knockdown
      on the activation status of CD4+ T cells and the progression of diabetes. During
      the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually
      increased and the CD4+ T cells were gradually activated, resulting in more TH1
      cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced
      the blood glucose level, improved the function of islet beta cells and reduced
      the activation of CD4+ T cells. Early application of CatG siRNA improved the
      function of islet beta cells, reduced islet inflammation and beta cell apoptosis,
      and lowered the activation level of CD4+ T cells, thus slowing down the
      progression of diabetes.

PMID- 29218111
TI  - The diagnostic value of microRNA-4787-5p and microRNA-4306 in patients with acute
      aortic dissection.
AB  - Acute aortic dissection (AAD) is a life-threatening cardiovascular disease with
      the high morbidity and mortality. Imaging modalities are the gold standard for
      the diagnosis of AAD; however, they are not always available in emergency
      department. Biomarker-assisted diagnosis is important for the early treatment of
      AAD. The aim of the present study was to identify potential microRNA (miRNA)
      biomarkers for AAD. Differentially expressed plasma miRNAs between AAD patients
      and age-matched healthy volunteers were analyzed by miRNA microarray.
      Quantitative RT-PCR was further performed to verify the expression of selected
      miRNAs (miR-4787-5p and miR-4306) with an increased number of samples. Receiver
      operating characteristic (ROC) analysis was used to assess the diagnostic value
      of miR-4787-5p and miR-4306 as biomarkers for distinguishing AAD. Using
      TargetScan and miRanda, miR-4787-5p and miR-4306 were selected to predict target
      gene related to cytokines detecting by dual luciferase assay and western
      blotting. Nine upregulated and twelve downregulated miRNAs were identified in the
      circulating plasma of AAD patients. qRT-PCR verified statistically consistent
      expression of two selected miRNAs with microarray analysis. ROC analyses
      demonstrated that miR-4787-5p and miR-4306 were specific and sensitive for the
      early diagnosis of AAD. Bioinformatic predictions and dual luciferase assay
      suggested that polycystin-1 (PKD1) and transforming growth factor-beta1 (TGF
      beta1) were respectively direct target of miR-4787-5p and miR-4306. Furthermore,
      the protein expression of the downstream targets of PKD1 and TGF-beta1 were
      significantly reduced following overexpression of miR-4787-5p and miR-4306. These
      results revealed that miR-4787-5p and miR-4306 could be developed as diagnostic
      potential biomarkers for AAD, and they could be involved in the pathogenesis of
      AAD.

PMID- 29218112
TI  - Triptolide protects podocytes from TGF-beta-induced injury by preventing miR-30
      downregulation.
AB  - Triptolide is known to have a strong anti-proteinuric effect through direct
      protection of podocytes from injury and is used to treat glomerular diseases.
      However, the mechanism underlying its protective effect on podocytes remains
      elusive. MiR-30 family has recently been shown to be essential for structural and
      functional homeostasis of podocytes but is downregulated by injurious factors,
      leading to podocyte injury. In the present study, we explore whether Triptolide
      protects podocytes through preventing miR-30 downregulation. Since TGF-beta
      signaling is a critical mediator in various podocyte injuries and we previously
      found that TGF-beta induces podocyte injury through downregulating miR-30s, we
      thus used TGF-beta-induced podocyte injury model to address the issue. We found
      that Triptolide is capable of protecting cultured podocytes from TGF-beta-induced
      cytoskeletal injury and apoptosis, as expected. Consistently, Triptolide also
      prevented TGF-beta-induced signaling activation of MAPK p38, NFkB (p65) and
      calcineurin/NFATC3, which are known to be downstream mediators of podocyte
      injury. Meanwhile, Triptolide was found to completely prevent TGF-beta-induced
      miR-30 downregulation, indicating that Triptolide protects podocytes by
      sustaining miR-30 expression. Mechanistically, we found that Triptolide can
      prevent TGF-beta-induced Smad2/3 phosphorylation/activation, which likely
      underlies miR-30 restoration by Triptolide. We also performed ex vivo study and
      found that Triptolide prevented TGF-beta-induced miR-30 downregulation and
      Smad2/3 phosphorylation in the isolated glomeruli of mice or rats. Thus, our
      study has provided novel insights into the mechanism underlying the therapeutic
      effectiveness of Triptolide on podocytopathies.

PMID- 29218113
TI  - Age-associated alteration in Th17 cell response is related to endothelial cell
      senescence and atherosclerotic cerebral infarction.
AB  - T-helper 17 (Th17) cells produce Interleukin-17 (IL-17) that plays an important
      role in host-defense. However, little is known whether aging affects the
      functions of human Th17 cells. In this study, we examine age-associated
      alteration in Th17-cell response; correlation between Th17-cells and endothelial
      cell senescence; and the occurrence of acute cerebral infarction (ACI). First, we
      examined Th17-frequency, phenotyping, key transcription factors, and relevant
      cytokines in healthy elderly, middle-aged and young-people along with elderly
      patients with ACI. We detected levels of endothelial cell senescence markers in
      mRNA and inflammatory biomarker in serum among the groups. Correlations of Th17
      frequency to levels of cytokines and endothelial cell senescence biomarkers have
      been analyzed. Finally, effects of IL-17 on endothelial cell senescence were
      explored in vitro. Our study demonstrated that healthy elderly-people have an
      increased Th17 frequency, RORgammat expression and Th17 related cytokines (IL-17,
      IL-6) levels in peripheral blood compared to healthy middle-aged and young
      people. Furthermore, elderly-ACI patients also have an increased Th17 expression
      as compared to healthy elderly-people. There was no significant difference in
      levels of memory Th17 frequency among the 4 groups, indicating that IL-17 is
      mainly produced by memory CD4+ T cells. There were no significant correlations
      between Th17 frequencies, levels of cytokines, inflammatory biomarkers in serum
      and endothelial cell senescence biomarkers in mRNA. Cell experiments about human
      umbilical vein endothelial cells (HUVECs) co-culture with IL-17 demonstrated that
      IL-17 promotes endothelial cell senescence which is closely related to ACI
      occurrence. Our results suggested that aging and ACI occurrence strengthen Th17
      cell response. Th17/IL-17 may promote endothelial cell senescence, subsequently
      contributing to ACI occurrence in humans.

PMID- 29218114
TI  - Comparative transcriptome analysis of the global circular RNAs expression
      profiles between SHEE and SHEEC cell lines.
AB  - Esophageal squamous cell carcinoma (ESCC) is widely regarded as one of the most
      lethal types of cancer around the world. The fact that early detection of ESCC
      could dramatically improve the treatment outcome of the patients has sparked
      considerable interest in searching for reliable and accurate diagnostic
      biomarkers. Recently, circular RNAs (circRNA) have emerged as a new type of non
      coding RNAs with significant RNase resistance, wide abundance and remarkable
      internal diversity. There is also increasing evidence suggesting that circRNAs
      could be implicated in the pathogenesis of cancer and other diseases. In this
      study, we performed a comparative analysis of the global circRNA expression
      profiles in normal and malignant esophageal epithelial cell lines by a
      combination of RNA sequencing and bioinformatics analysis. We identified 813
      significantly up-regulated and 445 down-regulated circRNA candidates, of which 32
      were subsequently validated by quantitative real-time reverse transcription
      polymerase chain reaction analysis. The differentially expressed circRNAs were
      found to be associated with pathways involved in metabolism, cell apoptosis,
      proliferation and migration, which are commonly altered in cancer cells. Based on
      the obtained data, we constructed a circRNA-miRNA interaction network, in which
      circRNA9927-NBEAL1 represented the biggest node. Our study could lay the
      groundwork for further investigation concerning the pathological roles of
      circRNAs in ESCC.

PMID- 29218115
TI  - Erratum: Preventive effects of kudzu root on bone loss and cartilage degradation
      in ovariectomized rats.
AB  - [This corrects the article on p. 3517 in vol. 9, PMID: 28804568.].

PMID- 29218116
TI  - Erratum: New insights and new hope for pulmonary arterial hypertension:
      natriuretic peptides clearance receptor as a novel therapeutic target for a
      complex disease.
AB  - [This corrects the article on p. 112 in vol. 9, PMID: 28951773.].

PMID- 29218118
TI  - New Treatments on the Horizon for Familial Hypercholesterolemia.

PMID- 29218119
TI  - Carpal Tunnel Syndrome and Other Entrapment Neuropathies.
AB  - Entrapment neuropathy is the result of pressure on a peripheral nerve as it
      passes through a narrow canal that is bounded by stiff tissues. In spite of their
      ubiquitous nature, they are underdiagnosed, underreported, and sometimes not
      properly managed, especially in developing countries. Entrapment neuropathies are
      of various types, but the most common type is carpal tunnel syndrome. Mechanisms
      involved in the pathophysiology of entrapment neuropathies include mechanical
      compression and nerve ischemia. A clear understanding of the various types and
      the underlying mechanisms of entrapment neuropathies are invaluable in the
      decision-making process involved in the management of every patient with the
      condition.

PMID- 29218117
TI  - Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention
      (AMP) Test-of-Concept Efficacy Trials.
AB  - Background: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been
      developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine
      Trials Network and the HIV Prevention Trials Network are conducting the Antibody
      Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion
      of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the
      first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans.
      Methods: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy
      trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons
      who have sex with men in the United States, Peru, Brazil, and Switzerland; and
      1500 HIV-uninfected sexually active women in seven countries in sub-Saharan
      Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of
      10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a
      total of 10 infusions. Each trial is designed (1) to assess overall prevention
      efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess
      VRC01 dose and laboratory markers as correlates of protection (CoPs) against
      overall and genotype- and phenotype-specific infection. Results: Each AMP trial
      is designed to have 90% power to detect PE > 0% if PE is >= 60%. The AMP trials
      are also designed to identify VRC01 properties (i.e., concentration and effector
      functions) that correlate with protection and to provide insight into mechanistic
      CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including
      genetic sequences and sensitivities to VRC01-mediated neutralization and Fc
      effector functions. Conclusions: The AMP trials test whether VRC01 can prevent
      HIV-1 infection in two study populations. If affirmative, they will provide
      information for estimating the optimal dosage of VRC01 (or subsequent
      derivatives) and identify threshold levels of neutralization and Fc effector
      functions associated with high-level protection, setting a benchmark for future
      vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1
      prevention.

PMID- 29218120
TI  - Characteristics and Correlates of Woman Eligible for Targeted Screening
      Mammography in Oman.
AB  - Objectives: We sought to determine the characteristics of women eligible for a
      high-yield screening mammography program in Oman. Methods: We conducted a
      retrospective review of women who underwent breast cancer screening at the Oman
      Cancer Association from 22 December 2009 to 6 February 2011. Women with a Breast
      Imaging Reporting and Data System (BI-RADS) score of 4-5 were compared with those
      with a score of 1-3 based on well-known breast cancer risk factors using the case
      control approach analysis. Results: A BI-RADS score of 4-5 was found in 16.2% of
      women screened for breast cancer. A higher likelihood of a BI-RADS score of 4 or
      5 was observed among women who did not breastfeed (odds ratio (OR) = 2.564; 95%
      confidence interval (CI): 1.690, 3.890), had their first pregnancy at an older
      age (OR = 1.062; 95% CI: 1.041, 1.083), used oral contraceptives (OR = 1.397; 95%
      CI: 1.008, 1.938), and those who reported a positive family history of
      malignancies (OR = 1.633; 95% CI: 1.285, 2.076). A BI-RADS score of 4 or 5 was
      significantly less likely in women with a higher number of full-term pregnancies
      (OR = 0.919; 95% CI: 0.890, 0.948). BI-RADS 4-5 were independently predicted in
      women with a lower number of full-term pregnancies, did not breastfeed, used oral
      contraceptives, and who had a positive family history of malignancies. These
      variables explained 84.0% of the variation in mammogram results. Conclusions: In
      the absence of a national screening program for breast cancer, the high-risk
      approach for screening should be considered. Women with the above characteristics
      should be identified and motivated to seek mammogram regularly to warrant a
      better outcome.

PMID- 29218121
TI  - Characteristics of Chronic Pain Patients Attending a Primary Health Care Center
      in Oman.
AB  - Objectives: To determine the characteristics of patients presenting with chronic
      pain in a primary health care setting in Oman. Methods: A retrospective cross
      sectional study was carried out including all patients aged >= 18 years who
      attended Sultan Qaboos University Health Center during 2010. Patients were
      identified to have chronic pain if they were prescribed an analgesic medication
      for at least three months. Patients were compared to a control group which
      consisted of age- and gender-matched patients with no chronic pain. Results: Out
      of 6 609 patients, 241 (3.6%) were found to have chronic pain. The mean age of
      patients with chronic pain was 54.0+/-13.0 years. The majority of patients were
      female (n = 174; 72.1%), and most were Omani (n = 201; 83.4%). The prevalence of
      chronic pain was found to be significantly higher among females compared to males
      (4.5% vs. 2.5%; p < 0.001) and also among Omani nationals to non-nationals (83.4%
      vs. 70.1%; p < 0.001). Chronic pain was significantly associated with the
      following comorbidities; diabetes (33.1% vs. 20.7%; p < 0.001), obesity (35.2%
      vs. 26.5%; p = 0.001), and hypertension (51.0% vs. 38.5%; p = 0.002).
      Osteoarthritis was the most common pain condition (n = 104; 43.1%). Diclofenac
      was the most commonly prescribed drug (n = 168; 69.7%). Conclusions: The findings
      of our study point towards a higher prevalence of chronic pain in Omani females.
      These patients were also found to have a higher prevalence of other common
      comorbid conditions.

PMID- 29218122
TI  - Effect of Growth Hormone on Final Height in Children with Idiopathic Short
      Stature: A UAE, Eastern Region Experience.
AB  - Objectives: The use of growth hormone (GH) in idiopathic short stature (ISS) has
      been a subject of debate for the past two decades. We sought to assess the effect
      of GH on final height (FH) in patients with ISS in our region, which has a high
      consanguinity rate, and compare it to the effect observed in GH deficient (GHD)
      patients. Methods: We conducted a retrospective chart review from 1 January 2005
      to 31 December 2013 for patients with ISS or GHD from the local United Arab
      Emirates population who received GH treatment and were followed-up regularly in
      our clinic. The change in height Z-score at 12 months and FH were assessed within
      each group and between the two groups. Results: Twenty-one patients with ISS and
      29 patients with GHD were studied. There was a significant change in height Z
      score at 12 months and FH in both groups (p < 0.001). The improvement in the ISS
      group was comparable to the response seen in GHD patients at 12 months (0.5+/-0.3
      standard deviation score (SDS), and 0.5+/-0.4 SDS, respectively; p = 0.540). The
      effect on FH was better in ISS group than the GHD group of all etiologies (1.3+/
      0.6 SDS vs. 0.9+/-0.7 SDS, respectively; p = 0.050), there was no difference
      between the ISS and the subgroup of idiopathic GHD (1.3+/-0.5 SDS and 1.2+/-0.8
      SDS, respectively). Conclusions: In our local population, GH has a positive
      effect on the short-term growth and FH of children with ISS to the same extent
      that has been observed in children with idiopathic GH deficiency.

PMID- 29218123
TI  - Acceptability of Reminders for Immunization Appointments via Mobile Devices by
      Mothers in Ilorin, Nigeria: A Cross-sectional Study.
AB  - Objectives: Immunization coverage in Nigeria remains low despite the protection
      it confers. Reminders via mobile phones may be deployed as a means of improving
      vaccination coverage but requires the participation and cooperation of the
      caregiver. Therefore, we evaluated the acceptability of reminders for
      immunization appointment by mothers in Ilorin, Nigeria. Methods: This descriptive
      cross-sectional study recruited 526 mothers from two public hospitals in Ilorin.
      Semi-structured questionnaires were used to collect information on ownership and
      access to phones, willingness to receive reminders, household, antenatal, and
      delivery characteristics. Results: The majority (92.7%) of mothers had a personal
      phone, and all willingly provided contact details. Over half (69.0%) of mothers
      were willing to receive reminders. Postsecondary education (odds ratio (OR) =
      1.958; 95% confidence interval (CI): 1.232-3.111) and antenatal care attendance
      by mothers (OR = 8.381; 95% CI: 2.495-28.170) were significant determinants of
      mothers willingness to receive reminders. Mothers with less than or equal to four
      children had a three-fold increased odds of wanting reminders. Artisan mothers
      were less likely to want reminders compared with unemployed mothers (OR = 0.506;
      95% CI: 0.291-0.847). Conclusions: Most mothers are willing to receive reminders
      on immunization appointments via their mobile phone. Determinants of maternal
      willingness to receive reminders include mothers with less than four children,
      postsecondary education, and antenatal care attendance. Program planners should
      consider utilizing reminders as a strategy to increase the immunization uptake
      with access to contact details making this feasible.

PMID- 29218124
TI  - Expression of Toll-like Receptor 2 and 4 in Peripheral Blood Neutrophil Cells
      from Patients with Chronic Obstructive Pulmonary Disease.
AB  - Objectives: Chronic obstructive pulmonary disease (COPD) is one of the leading
      causes of morbidity and mortality around the world. Preliminary studies have
      evaluated the association between innate immunity including Toll-like receptors
      (TLRs) and airway samples of patients with COPD. The role of TLRs in peripheral
      blood neutrophils is poorly understood. Hence, this study aimed to investigate
      the role of TLR2 and TLR4 in peripheral blood neutrophils of COPD patients.
      Methods: A total of 101 COPD cases and an equal number of healthy controls
      participated in this case-control study. Peripheral blood neutrophils were
      isolated from all participants and cultured for 24 hours through
      lipopolysaccharide (LPS) stimulation. The gene expressions of TLR2 and TLR4 were
      assessed by real-time polymerase chain reaction. The protein levels of
      interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 were measured in
      neutrophils cell culture supernatants using enzyme-linked immunosorbent assay
      (ELISA). Results: The levels of IL-8 and MMP-9 were significantly higher in
      patients with COPD compared to healthy controls. Similarly, the gene expression
      of TLR2 and TLR4 were increased in LPS stimulated peripheral blood neutrophils of
      patients with COPD. Smoke pack years was positively correlated with IL-8 levels
      and negatively correlated with forced expiratory volume in the first second % (r
      = -0.33; p = 0.023) and FEV1/forced vital capacity (FVC) (r = -0.27; p = 0.011).
      Conclusions: The increased expression of TLR2 and TLR4 suggests its role in
      disease pathogenesis of COPD. Smoke pack years was negatively associated with
      spirometric parameters in COPD patients. This may help to predict the smokers
      without COPD who risk developing the condition in the future.

PMID- 29218125
TI  - The Seroprevalence and Risk Factors of Toxoplasmosis Among Female Undergraduate
      University Students in Saudi Arabia.
AB  - Objectives: Toxoplasma gondii (T. gondii) is a serious public health issue, but
      limited data has been published to date on the seroprevalence of T. gondii
      infection in Saudi Arabia. Therefore, this study aimed to establish the
      seroprevalence and risk factors of T. gondii infection using a sample of females
      enrolled at a university in Northern Saudi Arabia. Methods: Using a cross
      sectional research approach, we recruited a convenience sample of 180 healthy
      females studying at the University of Tabuk between February and June 2016. We
      used a questionnaire to gather sociodemographic data on the participants to
      establish the risk factors leading to exposure to toxoplasma. Blood samples were
      taken from the participants and analyzed to detect T. gondii antibodies
      (immunoglobulin M and immunoglobulin G) via the enzyme-linked immunosorbent assay
      technique. Multivariate logistic regression modeling was employed to establish
      the potential predictor variables for T. gondii infection. Results: Of the 180
      participants, 17 (9.4%) were seropositive for T. gondii IgG. None tested positive
      for IgM antibodies exclusively. The sole variable positively associated with
      seropositive T. gondii IgG was the participants' consumption of raw, unwashed
      fruit or vegetables (odds ratio = 3.36, 95% confidence interval: 1.11-10.22).
      Conclusions: Our findings emphasize the need for higher awareness of
      toxoplasmosis in Saudi Arabia, specifically knowledge of the way toxoplasma
      infection occurs so that women can more easily avoid it. Large-scale research is
      therefore required to inform the design of future public health interventions.

PMID- 29218126
TI  - A Pilot Study Comparing Hysteroscopic Adhesiolysis by Conventional Resectoscope
      Versus Mini-resectoscope.
AB  - Objectives: To compare the feasibility and efficacy of the mini-resectoscope with
      the conventional resectoscope in terms of the operative, menstrual, and
      reproductive outcome in hysteroscopic adhesiolysis in infertile women. Methods:
      We conducted a parallel prospective randomized study at All India Institute of
      Medical Sciences, New Delhi. A total of 60 patients underwent hysteroscopic
      adhesiolysis using either conventional resectoscope (n = 30) or mini-resectoscope
      (n = 30). The primary outcome measures were pregnancy-related indicators.
      Secondary outcome measures were the operative parameters (cervical dilatation
      time, operation time, postoperative pain scores, fluid deficit, and preoperative
      and postoperative sodium levels), second-look hysteroscopy findings, and
      improvement in the menstrual pattern after surgery. Results: Cervical dilatation
      time and pain score 30 minutes after the procedure were significantly lower in
      the mini-resectoscope group. Out of the total 21 cases with hypomenorrhea, 12
      cases (57.1%) started having normal menstrual flow postsurgery. All amenorrheic
      patients resumed menstruation after surgery. However, nine cases continued to
      have hypomenorrhea. Over long-term follow-up, 16 patients out of 60 had conceived
      (seven in the conventional resectoscope group and nine in the mini-resectoscope
      group). There were three ongoing pregnancies, three abortions, one ectopic
      pregnancy, and nine term pregnancies. The difference between the two groups was
      not statistically significant. Conclusions: The use of mini-resectoscope for
      hysteroscopic adhesiolysis is associated with reduced operative morbidity. Use of
      the mini-resectoscope is an effective and safe alternative to the conventional
      system.

PMID- 29218127
TI  - The Effect of Group Discussion-based Education on Self-management of Adults with
      Type 2 Diabetes Mellitus Compared with Usual Care: A Randomized Control Trial.
AB  - Objectives: We sought to determine the effect of group discussion-based education
      on the self-management capability of patients with type 2 diabetes in Iran.
      Methods: This randomized control trial was conducted on 90 patients with type 2
      diabetes. Participants were allocated randomly into one of two groups;
      intervention and control. The intervention group received the group discussion
      based education while the control group received routine care only. The Lin's
      self-management questionnaire was completed at baseline and three months post
      intervention. Results: Statistical analysis, including the use of independent t
      test, identified that in comparison to the control group, significant increases
      were observed in the scores of self-organization (t =11.24, p < 0.001), self
      adjustment (t = 7.53, p < 0.001), interaction with health experts (t = 7.31, p <
      0.001), blood sugar self-monitoring (t = 6.42, p < 0.001), adherence to the
      proposed diet (t = 5.22, p < 0.001), and total self-management (t = 10.82, p <
      0.001) in the intervention group. Conclusions: Sharing experiences through group
      discussions and receiving instructive feedback can improve the ability to self
      manage diabetes.

PMID- 29218128
TI  - Neurobrucellosis Presenting as Pseudotumor Cerebri: First Report from Oman.
AB  - A ten-year-old boy presented to the hospital with body ache and joint pains for
      two months and headache, vomiting, and skin rash for three days. He was drowsy
      and lethargic at admission. Physical examination revealed bilateral papilledema.
      There were no cranial nerve involvement, neuromotor deficit, or signs of
      meningeal irritation. Computed tomography and magnetic resonance imaging of the
      brain did not reveal any evidence of cerebral edema or space occupying lesion. In
      view of the high endemicity of brucellosis in the area, Brucella agglutination
      test (BAT) was done at the time of admission and was negative. However, on the
      eighth day of admission, blood culture showed growth of Brucella melitensis. A
      repeat BAT at this time was strongly positive with a titer of 1:1 280. The
      initial one was negative due to prozone phenomenon caused by very high antibody
      titers. A diagnosis of neurobrucellosis with pseudotumor cerebri was made. He was
      treated with gentamicin, rifampicin, and septrin along with acetazolamide for
      raised intracranial pressure. The boy responded well to therapy and made a
      complete clinical recovery with resolution of papilledema. In areas endemic for
      brucellosis, a high index of suspicion for neurobrucellosis should be entertained
      in any child presenting with diverse neurological signs.

PMID- 29218129
TI  - Pubic Symphysis Diastasis: A Case Series and Literature Review.
AB  - Separation of pubic symphysis during delivery is a rare complication resulting in
      considerable and prolonged morbidity for parturient women. The usual presentation
      is that of something giving way in the region of the symphysis pubis sometimes
      with an audible crack at the time of delivery. Unbearable pain on moving from
      side-to-side and on performing any weight-bearing activity (such as walking or
      climbing stairs) precludes ambulation in the immediate postpartum period. This
      could be accompanied by disruption of the sacroiliac joint, hemorrhage, or urine
      incontinence in severe cases. Radiography, ultrasound, and magnetic resonance
      imaging are the diagnostic modalities that aid confirmation of diagnosis. The
      magnitude of separation does not correlate well with the severity of symptoms.
      Treatment modalities range from conservative management (including analgesics,
      pelvic binders, transcutaneous nerve stimulation) and chiropractic management to
      orthopedic interventions such as external fixation or open reduction and internal
      fixation. Since postpartum pain is frequently dismissed as attributable to labor
      and childbirth, the diagnosis of pubic symphysis diastasis is often delayed and
      sometimes missed altogether. Since there is no consensus in the scientific
      literature on the definition, etiopathogenesis, and management of this rare
      complication, we attempted to review the literature on the subject and present a
      series of two cases.

PMID- 29218130
TI  - Neonatal Stridor in Familial Congenital Laryngeal Paralysis (Plott Syndrome): ?A
      Case Study in an Omani Family.
AB  - Stridor presenting soon after birth due to bilateral abductor vocal cord
      paralysis (VCP) is rare. We report a family with bilateral VCP affecting four
      male members in two generations and hence suggesting X-linked recessive
      inheritance. Severe stridor in the neonatal period requires meticulous airway
      evaluation, and tracheostomy in 35-70% cases. The current trend is towards
      conservative management and tracheostomy is avoided unless respiratory distress
      is severe or life-threatening. Neonatal VCP can be an isolated finding, or it can
      be familial with or without syndromic features. There are very few reports of non
      syndromic familial cases. Unlike the cases reported previously, none of our
      patients required prolonged intubation or tracheostomy suggesting an excellent
      prognosis in such cases. This is the first case study of congenital familial non
      syndromic VCP reported from the Middle East.

PMID- 29218131
TI  - Hypocalcemia Associated with Subcutaneous Fat Necrosis of the Newborn: Case
      Report and Literature Review.
AB  - Subcutaneous fat necrosis of the newborn (SCFNN) is a rare benign inflammatory
      disorder of the adipose tissue but may be complicated by hypercalcemia or less
      frequently, hypocalcemia, resulting in morbidity and mortality. Here we report
      the case of a neonate with subcutaneous fat necrosis who surprisingly developed
      hypocalcemia instead of hypercalcemia. A full-term female neonate was delivered
      by emergency cesarean section for fetal distress and was subsequently admitted to
      the Special Care Baby Unit. The mother's pregnancy was uncomplicated up to
      delivery. Her anthropometric measurements were birth weight 4.1 kg (95th
      percentile), length 50 cm (50th percentile), and head circumference 34.5 cm (50th
      percentile). The Apgar scores were 2, 3, and 8 at 1, 5, 10 minutes, respectively.
      There was no abnormal facies and she was fed with breast milk only. On the
      seventh day of life, the infant was found to have multiple nodules located in the
      neck, upper back, and right arm. The nodules were firm, well circumscribed with
      no evidence of tenderness. Her total serum calcium level was 1.55 mmol/L (normal
      range 2.2 to 2.7 mmol/L) and this was associated with hypotonia and poor sucking
      reflex. The packed cell volume was 40%. The serum albumin and blood glucose
      levels were normal. Her blood culture was sterile. A clinical diagnosis of
      hypocalcemia associated with SCFNN was made. The infant was treated for
      hypocalcemia (using calcium gluconate) and was carefully followed-up. The skin
      lesions resolved completely three months after their eruption. Repeat serum
      calcium measurements at three, six, and nine months of age were all within normal
      limits. Although SCFNN is a rare benign clinical condition, it may be complicated
      by hypocalcemia. Therefore, periodic measurements of the serum calcium levels is
      warranted in such a patient, beginning from the neonatal period up to the age of
      six months.

PMID- 29218132
TI  - Portal Vein Thrombosis in Adult Omani Patients: A Retrospective Cohort Study.
AB  - OBJECTIVES: We sought to study the occurrence of portal vein thrombosis (PVT) in
      adult Omani patients. Methods: We conducted a retrospective cross-sectional study
      in patients diagnosed with PVT, which was confirmed by radiological imaging, from
      two tertiary hospitals over a 10-year period. Results: Amongst the 39 patients
      enrolled in the study, 15 (38.4%) had cirrhosis of the liver, and 24 (61.5%) were
      non-cirrhotic. In the non-cirrhotic PVT patients, 15 (62.5%) had acute PVT,
      whereas nine (37.5%) had chronic PVT. PVT was more common in males than females,
      (25 (64.1%) vs. 14 (35.8%), respectively, p = 0.020). The three most common
      clinical symptoms were abdominal pain (n = 25, 64.1%) followed by nausea (n = 12,
      30.7%) and fever (n = 8, 20.5%) patients. Causative risk factors included
      prothrombotic states (17.9-28.2%) and local factors (20.5%) such as
      cholecystitis, cholangitis, and liver abscess. Complications were found in 23.0%
      of patients with PVT, namely variceal bleeding in seven patients (17.9%) patients
      and bowel ischemia in two patients (5.1%). Management with sclerotherapy was
      performed in all patients with variceal bleeding. Thrombectomy was done for one
      patient complicated with intestinal ischemia, but as it failed, he was treated
      with warfarin anticoagulation. CONCLUSIONS: This is the first study reflecting a
      real-life practice in PVT with possibly underlying inherited and acquired
      prothrombotic conditions as well as complications due to local and malignant
      conditions from Oman. We studied the prevalence, clinical presentation,
      underlying possible etiological factors, treatment, and outcomes. Since causative
      factors were found in 36 patients (92.3%), etiological screening seems worthwhile
      in every case with PVT, but thrombophilia screening may not be cost-effective.

PMID- 29218133
TI  - A Woman with Abdominal Pain, Vomiting and "Air Under Diaphragm".

PMID- 29218134
TI  - Antibiotic Resistance: A Real Menace.

PMID- 29218135
TI  - Langerhans cell sarcoma of the skin in association with superficial atypical
      Langerhans cell proliferation.

PMID- 29218136
TI  - Assessing the impact of a waiting time survey on reducing waiting times in urban
      primary care clinics in Cape Town, South Africa.
AB  - A waiting time survey (WTS) conducted in several clinics in Cape Town, South
      Africa provided recommendations on how to shorten waiting times (WT). A follow-up
      study was conducted to assess whether WT had reduced. Using a stratified sample
      of 22 clinics, a before and after study design assessed changes in WT. The WT was
      measured and perceptions of clinic managers were elicited, about the previous
      survey's recommendations. The overall median WT decreased by 21 minutes (95%CI:
      11.77-30.23), a 28% decrease from the previous WTS. Although no specific factor
      was associated with decreases in WT, implementation of recommendations to reduce
      WT was 2.67 times (95%CI: 1.33-5.40) more likely amongst those who received
      written recommendations and 2.3 times (95%CI: 1.28-4.19) more likely amongst
      managers with 5 or more years' experience. The decrease in WT found demonstrates
      the utility of a WTS in busy urban clinics in developing country contexts.
      Experienced facility managers who timeously receive customised reports of their
      clinic's performance are more likely to implement changes that positively impact
      on reducing WT.

PMID- 29218137
TI  - Low temperature limits for root growth in alpine species are set by cell
      differentiation.
AB  - Plant growth in cold climates is not limited by carbon assimilation (source
      activity) but rather by reduced carbon investment into new tissues (sink
      limitation). It has been hypothesized that all cold-adapted plants face similar
      growth constraints at low temperature mainly associated with the formation of new
      tissues. To explore the thermal limitation of plant tissue formation, we studied
      root growth and anatomical root tissue characteristics in four cold-adapted
      alpine species (Ranunculus glacialis, Rumex alpinus, Tussilago farfara, Poa
      alpina), grown in thermostated soils with a vertical temperature gradient
      approaching 1  degrees C. Above-ground plant organs were exposed to typical
      alpine climate conditions (high solar radiation and cool nights) at 2440 m a.s.l.
      in the Swiss Alps to assure continuous source activity. Image-based measurements
      of root growth (root elongation rates at 12-h intervals, RERs) were combined with
      anatomical examinations in thermally constrained root tips as well as with a
      functional growth analysis of entire plants. Temperatures in the range 0.8 to 1.4
      degrees C were denoted as critically low temperature thresholds for root
      formation across the four species. The RERs per 12 h revealed that roots kept
      extending at low rates at 0.7-1.2  degrees C but cell elongation and xylem
      lignification were clearly inhibited in the terminal zones of root tips. Roots
      exposed to temperatures between 1 and 5  degrees C showed strongly reduced
      elongation rates so that these roots contributed very little to the entire root
      system compared to control roots grown at 10  degrees C. Hardly any secondary
      roots were formed at temperatures below 5  degrees C and total root mass was
      substantially lower (74 % reduction in comparison to control), also the above
      ground biomass was reduced by 23 %. Cell elongation and differentiation rather
      than cell division control length and shape of root cells at the low temperature
      limit of growth. Lignification of root xylem is clearly constrained at
      temperatures below 3  degrees C.

PMID- 29218138
TI  - Conspecific plants are better 'nurses' than rocks: consistent results revealing
      intraspecific facilitation as a process that promotes establishment in a hyper
      arid environment.
AB  - Harsh environmental conditions in arid ecosystems limit seedling recruitment to
      microhabitats under nurse structures, such as shrubs or rocks. These structures,
      however, do not necessarily afford the same benefits to plants because nurse
      rocks provide only physical nurse effects, whereas nurse plants can provide both
      physical and biological nurse effects. Nevertheless, if the nurse plant is a
      conspecific, the benefits it provides may be outweighed by higher mortality due
      to negative density-dependent processes; consequently, negative density
      dependence is expected to limit plants from acting as nurses to their own
      seedlings. The degree to which an abiotic nurse may be more beneficial than a
      conspecific one remains largely unexplored. Here, we examine the role and
      elucidate the mechanisms by which conspecific plants and rocks promote plant
      establishment in a hyper-arid desert. For 4 years, we examined establishment
      patterns of Myrcianthes coquimbensis (Myrtaceae), a threatened desert shrub that
      recruits solely in rock cavities and under conspecific shrubs. Specifically, we
      characterized these microhabitats, as well as open interspaces for comparison,
      and conducted germination, seed removal and seedling survival experiments. Our
      results revealed that conspecific shrubs and nurse rocks modified environmental
      conditions in similar ways; soil and air temperatures were lower, and water
      availability was higher than in open interspaces. We found no evidence on
      negative density-dependent recruitment: seed removal was lowest and seedling
      emergence highest under conspecific plants, moreover seedling survival
      probabilities were similar in rock cavities and under conspecific plants. We
      conclude that the probability of establishment was highest under conspecific
      plants than in other microhabitats, contrasting what is expected under the Janzen
      Connell recruitment model. We suggest that for species living in stressful
      environments, population regulation may be a function of positive density
      dependence and intraspecific facilitation may be a process that promotes the
      persistence of some plant species within a community.

PMID- 29218139
TI  - Herbivory by leaf-cutter ants changes the glandular trichomes density and the
      volatile components in an aromatic plant model.
AB  - Herbivory can induce several structural and functional alterations in the plant
      secretory system. Glandular trichomes are the main sites of production of
      volatile organic compounds (VOCs) with several chemical properties in Lamiaceae
      species. Ocimum species usually have three morphotypes of glandular trichomes
      (morphotype I is peltate and has a wide four-celled head; morphotype II is
      capitate and has a unicellular head; and morphotype III is capitate with a
      bicellular head) which produce a great amount of terpenes, although other
      chemical categories of substances are also produced. Despite the abundance of
      trichomes producing important anti-herbivory components in their leaves, the
      association between Ocimum species and leaf-cutter ants has been commonly
      registered in Brazil. We investigated the effect of leaf-cutter ant attack on the
      density of the glandular trichomes and on the chemistry of the VOCs released from
      leaves of O. gratissimum. Plants were subjected to Acromyrmex rugosus attack
      until 90 % of leaves were removed. After 40 days from the leaf-cutter attack,
      both treatments were sampled. The glandular trichome density was analysed by
      scanning electron microscopy. The VOCs were extracted utilizing headspace solid
      phase microextraction (HS-SPME) technique and analysed by gas chromatography.
      Generally, the density of glandular trichomes increased in the adaxial leaf
      surface of the attacked plants. However, we bring novelties on this topic since
      we analysed the density of each morphotype separately. The morphotype I decreased
      in the abaxial leaf surface, and increased in the adaxial leaf surface; the
      morphotype II increased in both leaf surfaces; and the morphotype III decreased
      in the abaxial leaf surface and remained constant in the adaxial leaf surface of
      attacked plants. In leaves of attacked plants, the (Z)-beta-ocimene increased by
      50 %, the alpha-selinene by 13 % and the germacrene D by 126 %, whereas the
      eugenol decreased by 70 %. Our data point to a differential response of each
      glandular morphotype in O. gratissimum and are consistent with the idea of a
      compartmentalization of functions among the different glandular morphotypes in
      the plant defence against environmental factors.

PMID- 29218140
TI  - Effects of white-tailed deer and invasive plants on the herb layer of suburban
      forests.
AB  - Lack of hunting and predators and proximity to human communities make suburban
      forests prone to high deer abundance and non-native plant invasions. I
      investigated these likely drivers of community structure in the herb layers of
      six suburban forests in one region of New Jersey, USA. In 223 plots I assessed
      the herb layer response to 2.5 years with or without deer fencing and the early
      stage of invasion from seed additions of Microstegium vimineum, an invasive,
      annual grass. Non-native plants and herbaceous native plants were affected very
      little by fencing or M. vimineum invasion. In contrast, across all forests the
      combination of deer access and M. vimineum addition had a strongly negative
      effect on woody native percent cover. Forests differed in overall fencing effects
      on woody natives; their cover was greater in fenced plots in just three forests,
      suggesting greater deer pressure in those forests during the experiment. The
      early invasion by M. vimineum was greatest in two of these same forests, but was
      not influenced by fencing. Multi-group structural equation modelling compared two
      groups of forests that differed in vegetation abundance and other
      characteristics. It paralleled the results above and also showed no negative
      influence of non-native cover on native cover, even in the forests where non
      native cover was greater. It identified a positive effect of light level on herb
      layer plants in the forests with less vegetation, and also revealed a positive
      effect of soil water potential (SWP) on non-native plants in the forests with
      more vegetation, which had higher SWP. These suburban forests within a common
      region varied widely in native and non-native herb layer abundance, the early
      success of M. vimineum invasion and the herb layer's response to early invasion
      and protection from deer.

PMID- 29218141
TI  - Enantioselective installation of adjacent tertiary benzylic stereocentres using
      lithiation-borylation-protodeboronation methodology. Application to the synthesis
      of bifluranol and fluorohexestrol.
AB  - 1,2-Diaryl ethanes bearing 1,2-stereogenic centres show interesting biological
      activity but their stereocontrolled synthesis has not been reported forcing a
      reliance of methods involving diastereomer and enantiomer separation. We have
      found that this class of molecules can be prepared with very high stereocontrol
      using lithiation-borylation methodology. The reaction of an enantioenriched
      benzylic lithiated carbamate with an enantioenriched benzylic secondary pinacol
      boronic ester gave a tertiary boronic ester with complete diastereo- and
      enantiocontrol. It was essential to use MgBr2/MeOH after formation of the
      boronate complex, both to promote the 1,2-migration and to trap any lithiated
      carbamate/benzylic anion that formed from fragmentation of the ate complex,
      anions that would otherwise racemise and re-form the boronate complex eroding
      both er and dr of the product. When the benzylic lithiated carbamate and benzylic
      secondary pinacol boronic ester were too hindered, boronate complex did not even
      form. In these cases, it was found that the use of the less hindered neopentyl
      boronic esters enabled successful homologation to take place even for the most
      hindered reaction partners, with high stereocontrol and without the need for
      additives. Protodeboronation of the product boronic esters with TBAF gave the
      target 1,2-diaryl ethanes bearing 1,2-stereogenic centres. The methodology was
      applied to the stereocontrolled synthesis of bifluranol and fluorohexestrol in
      just 7 and 5 steps, respectively.

PMID- 29218142
TI  - Bodipy-C60 triple hydrogen bonding assemblies as heavy atom-free triplet
      photosensitizers: preparation and study of the singlet/triplet energy transfer.
AB  - Supramolecular triplet photosensitizers based on hydrogen bonding-mediated
      molecular assemblies were prepared. Three thymine-containing visible light
      harvesting Bodipy derivatives (B-1, B-2 and B-3, which show absorption at 505 nm,
      630 nm and 593 nm, respectively) were used as H-bonding modules, and 1,6
      diaminopyridine-appended C60 was used as the complementary hydrogen bonding
      module (C-1), in which the C60 part acts as a spin converter for triplet
      formation. Visible light-harvesting antennae with methylated thymine were
      prepared as references (B-1-Me, B-2-Me and B-3-Me), which are unable to form
      strong H-bonds with C-1. Triple H-bonds are formed between each Bodipy antenna (B
      1, B-2 and B-3) and the C60 module (C-1). The photophysical properties of the H
      bonding assemblies and the reference non-hydrogen bond-forming mixtures were
      studied using steady state UV/vis absorption spectroscopy, fluorescence emission
      spectroscopy, electrochemical characterization, and nanosecond transient
      absorption spectroscopy. Singlet energy transfer from the Bodipy antenna to the
      C60 module was confirmed by fluorescence quenching studies. The intersystem
      crossing of the latter produced the triplet excited state. The nanosecond
      transient absorption spectroscopy showed that the triplet state is either
      localized on the C60 module (for assembly B-1.C-1), or on the styryl-Bodipy
      antenna (for assemblies B-2.C-1 and B-3.C-1). Intra-assembly forward-backward
      (ping-pong) singlet/triplet energy transfer was proposed. In contrast to the H
      bonding assemblies, slow triplet energy transfer was observed for the non
      hydrogen bonding mixtures. As a proof of concept, these supramolecular assemblies
      were used as triplet photosensitizers for triplet-triplet annihilation
      upconversion.

PMID- 29218143
TI  - Soft hydrogen bonds to alkenes: the methanol-ethene prototype under experimental
      and theoretical scrutiny.
AB  - An FTIR spectroscopic study of the elusive hydrogen-bonded methanol-ethene
      complex, the most elementary example for weak intermolecular alcohol hydrogen
      bonding to a pi cloud, is presented. By isolating the complex in a supersonic
      jet, the rigorous comparability to high-level quantum chemical calculations is
      ensured. In stark contrast to classical hydrogen bonds, experimental overtone
      analysis reveals the harmonic oscillator approximation for the OH red shift to be
      accurate. Harmonic calculations up to explicitly correlated local coupled-cluster
      level are thus found to agree very well with experiment. The experimental OH
      values for the red shift (45 cm-1), the small change in diagonal anharmonicity (
      3 cm-1) and the overtone intensity attenuation (2 * 102-fold) together with
      theoretical predictions for the preferred structural arrangement and the zero
      point-corrected dissociation energy (8 kJ mol-1) may thus be regarded as
      definitive reference values for related systems and for more approximate
      computational methods. In particular, MP2 calculations are shown to fail for this
      kind of weak intermolecular interaction.

PMID- 29218144
TI  - Counterion influence on the N-I-N halogen bond.
AB  - A detailed investigation of the influence of counterions on the [N-I-N]+ halogen
      bond in solution, in the solid state and in silico is presented. Translational
      diffusion coefficients indicate close attachment of counterions to the cationic,
      three-center halogen bond in dichloromethane solution. Isotopic perturbation of
      equilibrium NMR studies performed on isotopologue mixtures of regioselectively
      deuterated and nondeuterated analogues of the model system showed that the
      counterion is incapable of altering the symmetry of the [N-I-N]+ halogen bond.
      This symmetry remains even in the presence of an unfavorable geometric restraint.
      A high preference for the symmetric geometry was found also in the solid state by
      single crystal X-ray crystallography. Molecular systems encompassing weakly
      coordinating counterions behave similarly to the corresponding silver(i) centered
      coordination complexes. In contrast, systems possessing moderately or strongly
      coordinating anions show a distinctly different behavior. Such silver(i)
      complexes are converted into multi-coordinate geometries with strong Ag-O bonds,
      whereas the iodine centered systems remain linear and lack direct charge transfer
      interaction with the counterion, as verified by 15N NMR and DFT computation. This
      suggests that the [N-I-N]+ halogen bond may not be satisfactorily described in
      terms of a pure coordination bond typical of transition metal complexes, but as a
      secondary bond with a substantial charge-transfer character.

PMID- 29218145
TI  - Chemical speciation of MeHg+ and Hg2+ in aqueous solution and HEK cells nuclei by
      means of DNA interacting fluorogenic probes.
AB  - Selected new fluorogenic probes that interact in different ways with Hg2+ and
      MeHg+ have been prepared and used for the chemical speciation of both cations in
      aqueous solution as well as in HEK293 cells. The best selective speciation of
      Hg2+ and MeHg+ has been achieved by in vitro approaches based on fluorogenic
      probes supported in cultured cells, due to the particular sensitivity of the
      HEK293 cells to permeation by Hg2+, MeHg+ and the fluorogenic probes. In
      particular, MeHg+ was selectively detected in cell nuclei by probe JG45.

PMID- 29218146
TI  - Micro-competition system for Raman quantification of multiple glycans on intact
      cell surface.
AB  - A micro-competition system is designed for simultaneous quantification of
      multiple glycans on intact cell surfaces, by integrating two-surface-one-molecule
      competition with surface enhanced Raman scattering (SERS). The micro-competition
      is achieved among multiple-polysaccharide-coated gold nanostars functionalized
      silica bubbles, target cells and gold nanoprobes at a micron scale. The gold
      nanoprobes are prepared by coating distinct Raman molecules and lectins on gold
      nanoparticles for signal resolution and glycan recognition, respectively. The
      silica bubble surface serves as an artificial glycan surface and a SERS
      substrate. Upon the competitive recognition of lectin to the corresponding
      glycan, the gold nanoprobes can be specifically captured by the bubbles and cells
      in a homogeneous system, and the amounts of different gold nanoprobes on bubbles
      are simultaneously detected by SERS to reflect the corresponding glycan amounts
      on the cell surface. This micro-competition system with multiple quantification
      capability provides a powerful tool for investigation of the complex glycan
      related biological processes.

PMID- 29218147
TI  - Supramolecularly engineered phospholipids constructed by nucleobase molecular
      recognition: upgraded generation of phospholipids for drug delivery.
AB  - Despite of great advances of phospholipids and liposomes in clinical therapy,
      very limited success has been achieved in the preparation of smart phospholipids
      and controlled-release liposomes for in vivo drug delivery and clinical trials.
      Here we report a supramolecular approach to synthesize novel supramolecularly
      engineered phospholipids based on complementary hydrogen bonding of nucleosides,
      which greatly reduces the need of tedious chemical synthesis, including reducing
      the strict requirements for multistep chemical reactions, and the purification of
      the intermediates and the amount of waste generated relative more traditional
      approaches. These upgraded phospholipids self-assemble into liposome-like bilayer
      structures in aqueous solution, exhibiting fast stimuli-responsive ability due to
      the hydrogen bonding connection. In vitro and in vivo evaluations show the
      resulted supramolecular liposomes from nucleoside phospholipids could effectively
      transport drug into tumor tissue, rapidly enter tumor cells, and controllably
      release their payload in response to an intracellular acidic environment, thus
      resulting in a much higher antitumor activity than conventional liposomes. The
      present supramolecularly engineered phospholipids represent an important
      evolution in comparison to conventional covalent-bonded phospholipid systems.

PMID- 29218148
TI  - Systematic re-evaluation of the bis(2-hydroxyethyl)disulfide (HEDS) assay reveals
      an alternative mechanism and activity of glutaredoxins.
AB  - The reduction of bis(2-hydroxyethyl)disulfide (HEDS) by reduced glutathione (GSH)
      is the most commonly used assay to analyze the presence and properties of
      enzymatically active glutaredoxins (Grx), a family of central redox proteins in
      eukaryotes and glutathione-utilizing prokaryotes. Enzymatically active Grx
      usually prefer glutathionylated disulfide substrates. These are converted via a
      ping-pong mechanism. Sequential kinetic patterns for the HEDS assay have
      therefore been puzzling since 1991. Here we established a novel assay and used
      the model enzyme ScGrx7 from yeast and PfGrx from Plasmodium falciparum to test
      several possible causes for the sequential kinetics such as pre-enzymatic GSH
      depletion, simultaneous binding of a glutathionylated substrate and GSH, as well
      as substrate or product inhibition. Furthermore, we analyzed the non-enzymatic
      reaction between HEDS and GSH by HPLC and mass spectrometry suggesting that such
      a reaction is too slow to explain high Grx activities in the assay. The most
      plausible interpretation of our results is a direct Grx-catalyzed reduction of
      HEDS. Physiological implications of this alternative mechanism and of the Grx
      catalyzed reduction of non-glutathione disulfide substrates are discussed.

PMID- 29218149
TI  - Highly efficient near ultraviolet organic light-emitting diode based on a meta
      linked donor-acceptor molecule.
AB  - A novel near ultraviolet (NUV) emitter with a meta-linked donor-acceptor (D-A)
      structure between triphenylamine (TPA) and phenanthroimidazole (PPI), mTPA-PPI,
      was designed and synthesized. This molecular design is expected to resolve the
      conflict between the non-red-shifted emission and the introduction of a charge
      transfer (CT) state in the D-A system, aiming at NUV organic light-emitting
      diodes (OLEDs) with high-efficiency and colour-purity. Theoretical calculations
      and photophysical experiments were implemented to verify the unique excited state
      properties of mTPA-PPI. The mTPA-PPI device exhibited excellent NUV
      electroluminescence (EL) performance with an emission peak at 404 nm, a full
      width at half maximum (FWHM) of only 47 nm corresponding to a CIE coordinate of
      (0.161, 0.049), and a maximum external quantum efficiency (EQE) of 3.33%, which
      is among the best results for NUV OLEDs. This work not only demonstrates the
      promising potential of mTPA-PPI in NUV OLEDs, but also provides a valuable
      strategy for the rational design of NUV materials by using the meta-linked D-A
      architecture.

PMID- 29218150
TI  - Ammonia decomposition catalysis using non-stoichiometric lithium imide.
AB  - We demonstrate that non-stoichiometric lithium imide is a highly active catalyst
      for the production of high-purity hydrogen from ammonia, with superior ammonia
      decomposition activity to a number of other catalyst materials. Neutron powder
      diffraction measurements reveal that the catalyst deviates from pure imide
      stoichiometry under ammonia flow, with active catalytic behaviour observed across
      a range of stoichiometry values near the imide. These measurements also show that
      hydrogen from the ammonia is exchanged with, and incorporated into, the bulk
      catalyst material, in a significant departure from existing ammonia decomposition
      catalysts. The efficacy of the lithium imide-amide system not only represents a
      more promising catalyst system, but also broadens the range of candidates for
      amide-based ammonia decomposition to include those that form imides.

PMID- 29218151
TI  - Assembly line termination in cylindrocyclophane biosynthesis: discovery of an
      editing type II thioesterase domain in a type I polyketide synthase.
AB  - The termination step is an important source of structural diversity in polyketide
      biosynthesis. Most type I polyketide synthase (PKS) assembly lines are terminated
      by a thioesterase (TE) domain located at the C-terminus of the final module,
      while other PKS assembly lines lack a terminal TE domain and are instead
      terminated by a separate enzyme in trans. In cylindrocyclophane biosynthesis, the
      type I modular PKS assembly line is terminated by a freestanding type III PKS
      (CylI). Unexpectedly, the final module of the type I PKS (CylH) also possesses a
      C-terminal TE domain. Unlike typical type I PKSs, the CylH TE domain does not
      influence assembly line termination by CylI in vitro. Instead, this domain
      phylogenetically resembles a type II TE and possesses activity consistent with an
      editing function. This finding may shed light on the evolution of unusual PKS
      termination logic. In addition, the presence of related type II TE domains in
      many cryptic type I PKS and nonribosomal peptide synthetase (NRPS) assembly lines
      has implications for pathway annotation, product prediction, and engineering.

PMID- 29218152
TI  - Luminescent platinum(ii) complexes with self-assembly and anti-cancer properties:
      hydrogel, pH dependent emission color and sustained-release properties under
      physiological conditions.
AB  - Supramolecular interactions are of paramount importance in biology and chemistry,
      and can be used to develop new vehicles for drug delivery. Recently, there is a
      surge of interest on self-assembled functional supramolecular structures driven
      by intermolecular metal-metal interactions in cellular conditions. Herein we
      report a series of luminescent Pt(ii) complexes [Pt(C^N^Npyr)(C
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      [HC^N^Npyr = 2-phenyl-6-(1H-pyrazol-3-yl)-pyridine)] containing pincer type
      ligands having pyrazole moieties. These Pt(ii) complexes exert potent
      cytotoxicity to a panel of cancer cell lines including primary bladder cancer
      cells and display strong phosphorescence that is highly sensitive to the local
      environment. The self-assembly of these complexes is significantly affected by pH
      of the solution medium. Based on TEM, SEM, ESI-MS, absorption and emission
      spectroscopy, and fluorescence microscopy together with cell based assays,
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      0000000000000000000000000000000000 NR)]+ complexes were observed to self-assemble
      into orange phosphorescent polymeric aggregates driven by intermolecular Pt(ii)
      Pt(ii) and ligand-ligand interactions in a low-pH physiological medium.
      Importantly, the intracellular assembly and dis-assembly of [Pt(C^N^Npyr)(C
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      accompanied by change of emission color from orange to green. These
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      0000000000000000000000000000000000 NR)]+ complexes accumulated in the lysosomes
      of cancer cells, increased the lysosomal membrane permeability and induced cell
      death. One of these platinum(ii) complexes formed hydrogels which displayed pH
      responsive and sustained release properties, leading to low-pH-stimulated and
      time-dependent cytotoxicity towards cancer cells. These hydrogels can function as
      vehicles to deliver anti-cancer agent cargo, such as the bioactive natural
      products studied in this work.

PMID- 29218153
TI  - Cytotoxicity of guanine-based degradation products contributes to the
      antiproliferative activity of guanine-rich oligonucleotides.
AB  - Guanine-rich oligonucleotides (GROs) have attracted considerable attention as
      anticancer agents, because they exhibit cancer-selective antiproliferative
      activity and can form G-quadruplex structures with higher nuclease resistance and
      cellular uptake. Recently, a GRO, AS1411 has reached phase II clinical trials for
      acute myeloid leukemia and renal cell carcinoma. The antiproliferative activity
      of GROs has been associated with various protein targets; however the real
      mechanisms of action remain unclear. In this study, we showed evidence that
      antiproliferative activity of GROs (including AS1411) is mainly contributed by
      the cytotoxicity of their guanine-based degradation products, such as
      monophosphate deoxyguanosine (dGMP), deoxyguanosine (dG) and guanine. The GROs
      with lower nuclease resistance exhibited higher antiproliferative activity. Among
      nucleotides, nucleosides and nucleobases, only guanine-based compounds showed
      highly concentration-dependent cytotoxicity. Our results suggest that it is
      necessary to reconsider the cancer-selective antiproliferative activity of GROs.
      Since guanine-based compounds are endogenous substances in living organisms,
      systematic studies of the cytotoxicity of these compounds will provide new
      information for the understanding of certain diseases and offer useful
      information for drug design.

PMID- 29218154
TI  - A two-dimensional molecular beacon for mRNA-activated intelligent cancer
      theranostics.
AB  - Ideal theranostics should possess directly correlated imaging and therapy
      modalities that could be simultaneously activated in the disease site to generate
      high imaging contrast and therapeutic efficacy with minimal side effects.
      However, so far it still remains challenging to engineer all these
      characteristics into a single theranostic probe. Herein, we report a new type of
      photosensitizer (PS)-derived "two-dimensional" molecular beacon (TMB) that could
      be specifically activated within tumor cells to exhibit both high imaging
      contrast and therapeutic efficacy that outperforms conventional photosensitizers
      for cancer theranostics. The TMB is constructed by integrating a photosensitizer
      (chlorin e6 (Ce6)), a quantum dot (QD), and a dark quencher (BHQ3) into a hairpin
      DNA molecule to generate multiple synergistic FRET modes. The imaging modality
      and therapy modality, which are mediated by FRET between the QD and BHQ3 and FRET
      between the QD and Ce6 respectively, are interconnected within the TMB and could
      be simultaneously activated by tumor mRNA molecules. We show that highly
      effective cancer imaging and therapy could be achieved for cancer cell lines and
      xenografted tumor models. The reported TMB represents an unprecedented
      theranostic platform for intelligent cancer theranostics.

PMID- 29218155
TI  - Insights on spin polarization through the spin density source function.
AB  - Understanding how spin information is transmitted from paramagnetic to non
      magnetic centers is crucial in advanced materials research and calls for novel
      interpretive tools. Herein, we show that the spin density at a point may be seen
      as determined by a local source function for such density, operating at all other
      points of space. Integration of the local source over Bader's quantum atoms
      measures their contribution in determining the spin polarization at any system's
      location. Each contribution may be then conveniently decomposed in a magnetic
      term due to the magnetic natural orbital(s) density and in a reaction or
      relaxation term due to the remaining orbitals density. A simple test case, 3B1
      water, is chosen to exemplify whether an atom or group of atoms concur or oppose
      the paramagnetic center in determining a given local spin polarization.
      Discriminating magnetic from reaction or relaxation contributions to such
      behaviour strongly enhances chemical insight, though care needs to be paid to the
      large sensitivity of the latter contributions to the level of the computational
      approach and to the difficulty of singling out the magnetic orbitals in the case
      of highly correlated systems. Comparison of source function atomic contributions
      to the spin density with those reconstructing the electron density at a system's
      position, enlightens how the mechanisms which determine the two densities may in
      general differ and how diverse may be the role played by each system's atom in
      determining each of the two densities. These mechanisms reflect the quite diverse
      portraits of the electron density and electron spin density Laplacians, hence the
      different local concentration/dilution of the total and (alpha-beta) electron
      densities throughout the system. Being defined in terms of an observable, the
      source function for the spin density is also potentially amenable to experimental
      determination, as customarily performed for its electron density analogue.

PMID- 29218156
TI  - Dual wavelength asymmetric photochemical synthesis with circularly polarized
      light.
AB  - Asymmetric photochemical synthesis using circularly polarized (CP) light is
      theoretically attractive as a means of absolute asymmetric synthesis and
      postulated as an explanation for homochirality on Earth. Using an asymmetric
      photochemical synthesis of a dihydrohelicene as an example, we demonstrate the
      principle that two wavelengths of CP light can be used to control separate
      reactions. In doing so, a photostationary state (PSS) is set up in such a way
      that the enantiomeric induction intrinsic to each step can combine additively,
      significantly increasing the asymmetric induction possible in these reactions.
      Moreover, we show that the effects of this dual wavelength approach can be
      accurately determined by kinetic modelling of the PSS. Finally, by coupling a PSS
      to a thermal reaction to trap the photoproduct, we demonstrate that higher
      enantioselectivity can be achieved than that obtainable with single wavelength
      irradiation, without compromising the yield of the final product.

PMID- 29218157
TI  - Tailoring of the desired selectivity and the turn-on detection range in a self
      assembly-based fluorescence sensory system.
AB  - This study demonstrates how to control the selectivity and the turn-on detection
      range toward the tailoring of an assembly-based fluorescence (FL) sensory system.
      Assembly-based FL chemosensors composed of oligophenylenevinylene with a varied
      number of guanidinium receptors (G2, G4 and G6) were newly developed, and their
      FL response to nucleotides (AMP, ADP and ATP) was investigated. Indeed, G6
      exhibited FL emission via self-assembly with ATP. More importantly, the FL
      response of G6 showed markedly improved selectivity for ATP over ADP and a
      broadly extended detection range of ATP concentration under adjusted salt
      conditions. The salt effect on the FL response revealed the competitive binding
      interactions affecting the subsequent self-assembly process. These studies have
      unveiled the pivotal binding mechanisms operating in the self-assembly process,
      which tailor the performance level of the assembly-based sensory system. We
      believe that this study offers a new design principle of an assembly-based FL
      chemosensor with high selectivity and the appropriate detection range, being
      different from the conventional key-and-lock system.

PMID- 29218158
TI  - How to determine accurate chemical ordering in several nanometer large bimetallic
      crystallites from electronic structure calculations.
AB  - Chemical and physical properties of binary metallic nanoparticles (nanoalloys)
      are to a great extent defined by their chemical ordering, i.e. the pattern in
      which atoms of the two elements are located in a given crystal lattice. The
      reliable determination of the lowest-energy chemical ordering is a challenge that
      impedes in-depth studies of several-nm large bimetallic particles. We propose a
      method to efficiently optimize the chemical ordering based solely on results of
      electronic structure (density functional) calculations. We show that the accuracy
      of this method is practically the same as the accuracy of the underlying quantum
      mechanical approach. This method, due to its simplicity, immediately reveals why
      one or another chemical ordering is preferred and unravels the nature of the
      binding within the nanoparticles. For instance, our results provide very
      intuitive understanding of why gold and silver segregate on low-coordinated sites
      in Pd70Au70 and Pd70Ag70 particles, while Pd70Cu70 exhibits matryoshka-like
      structure and Pd70Zn70 features Zn and Pd atoms arranged in layers. To illustrate
      the power of the new method we optimized the chemical ordering in much larger
      Pd732Au731, Pd732Ag731, Pd732Cu731, and Pd732Zn731 nanocrystals, whose size ~4.4
      nm is common for catalytic applications.

PMID- 29218159
TI  - Unified total synthesis of the natural products endiandric acid A, kingianic acid
      E, and kingianins A, D, and F.
AB  - A measure of the strength of a synthetic strategy is its versatility:
      specifically, whether it allows structurally distinct targets to be prepared.
      Herein we disclose a unified approach for the total synthesis of natural products
      of three distinct structural types, all of which occur naturally as racemic
      mixtures. The point of divergence involves the terminal alkylation of a
      conjugated tetrayne, and culminates in a significantly shortened synthesis of
      endiandric acid A (8 steps), the first total synthesis of kingianic acid E (8
      steps), and a second-generation synthesis of kingianins A, D, and F (11 steps).
      Evidence for redox catalysis in the biosynthesis of kingianic acid E is
      presented.

PMID- 29218160
TI  - Thorium-ligand multiple bonds via reductive deprotection of a trityl group.
AB  - Reaction of [Th(I)(NR2)3] (R = SiMe3) (2) with KECPh3 (E = O, S) affords the
      thorium chalcogenates, [Th(ECPh3)(NR2)3] (3, E = O; 4, E = S), in moderate
      yields. Reductive deprotection of the trityl group from 3 and 4 by reaction with
      KC8, in the presence of 18-crown-6, affords the thorium oxo complex, [K(18-crown
      6)][Th(O)(NR2)3] (6), and the thorium sulphide complex, [K(18-crown
      6)][Th(S)(NR2)3] (7), respectively. The natural bond orbital and quantum theory
      of atoms-in-molecules approaches are employed to explore the metal-ligand bonding
      in 6 and 7 and their uranium analogues, and in particular the relative roles of
      the actinide 5f and 6d orbitals.

PMID- 29218161
TI  - Multiscale electrochemistry of hydrogels embedding conductive nanotubes.
AB  - The local functionalities of biocompatible objects can be characterized under
      conditions similar to the operating ones, using scanning electrochemical
      microscopy (SECM). In the case of alginate beads entrapping carbon nanotubes
      (CNTs), SECM allows evidencing of the local conductivity, organization, and
      communication between the CNTs. It shows that the CNT network is active enough to
      allow long range charge evacuation, enabling the use of alginate/CNT beads as
      soft 3D electrodes. Direct connection or local interrogation by a microelectrode
      allows visualization of their communication as a network and eventually the study
      of them individually at the nanoscale.

PMID- 29218162
TI  - The atomistic origin of the extraordinary oxygen reduction activity of Pt3Ni7
      fuel cell catalysts.
AB  - Recently Debe et al. reported that Pt3Ni7 leads to extraordinary Oxygen Reduction
      Reaction (ORR) activity. However, several reports show that hardly any Ni remains
      in the layers of the catalysts close to the surface ("Pt-skin effect"). This
      paradox that Ni is essential to the high catalytic activity with the peak ORR
      activity at Pt3Ni7 while little or no Ni remains close to the surface is
      explained here using large-scale first-principles-based simulations. We make the
      radical assumption that processing Pt-Ni catalysts under ORR conditions would
      leach out all Ni accessible to the solvent. To simulate this process we use the
      ReaxFF reactive force field, starting with random alloy particles ranging from
      50% Ni to 90% Ni and containing up to ~300 000 atoms, deleting the Ni atoms, and
      equilibrating the resulting structures. We find that the Pt3Ni7 case and a final
      particle radius around 7.5 nm lead to internal voids in communication with the
      exterior, doubling the external surface footprint, in fair agreement with
      experiment. Then we examine the surface character of these nanoporous systems and
      find that a prominent feature in the surface of the de-alloyed particles is a
      rhombic structure involving 4 surface atoms which is crystalline-like but under
      coordinated. Using density-functional theory, we calculate the energy barriers of
      ORR steps on Pt nanoporous catalysts, focusing on the Oad-hydration reaction (Oad
      + H2Oad -> OHad + OHad) but including the barriers of O2 dissociation (O2ad ->
      Oad + Oad) and water formation (OHad + Had -> H2Oad). We find that the reaction
      barrier for the Oad-hydration rate-determining-step is reduced significantly on
      the de-alloyed surface sites compared to Pt(111). Moreover we find that these
      active sites are prevalent on the surface of particles de-alloyed from a Pt-Ni 30
      : 70 initial composition. These simulations explain the peak in surface
      reactivity at Pt3Ni7, and provide a rational guide to use for further
      optimization of improved catalytic and nanoporous materials.

PMID- 29218163
TI  - A single crystalline porphyrinic titanium metal-organic framework.
AB  - We successfully assembled the photocatalytic titanium-oxo cluster and
      photosensitizing porphyrinic linker into a metal-organic framework (MOF), namely
      PCN-22. A preformed titanium-oxo carboxylate cluster is adopted as the starting
      material to judiciously control the MOF growth process to afford single crystals.
      This synthetic method is useful to obtain highly crystalline titanium MOFs, which
      has been a daunting challenge in this field. Moreover, PCN-22 demonstrated
      permanent porosity and photocatalytic activities toward alcohol oxidation.

PMID- 29218164
TI  - Chemical sensing in two dimensional porous covalent organic nanosheets.
AB  - Two new imide-based crystalline, porous, and chemically stable covalent organic
      frameworks (COFs) (TpBDH and TfpBDH) have been successfully synthesized employing
      solvothermal crystallization route. Furthermore, thin layered covalent organic
      nanosheets (CONs) were derived from these bulk COFs by the simple liquid phase
      exfoliation method. These 2D CONs showcase increased luminescence intensity
      compared to their bulk counterparts (COFs). Notably, TfpBDH-CONs showcase good
      selectivity and prominent, direct visual detection towards different
      nitroaromatic analytes over TpBDH-CONs. Quite interestingly, TfpBDH-CONs exhibit
      a superior "turn-on" detection capability for 2,4,6-trinitrophenol (TNP) in the
      solid state, but conversely, they also show a "turn-off" detection in the
      dispersion state. These findings describe a new approach towards developing an
      efficient, promising fluorescence chemosensor material for both visual and
      spectroscopic detection of nitroaromatic compounds with very low [10-5 (M)]
      analyte concentrations.

PMID- 29218165
TI  - Nitrogen fixation catalyzed by ferrocene-substituted dinitrogen-bridged
      dimolybdenum-dinitrogen complexes: unique behavior of ferrocene moiety as redox
      active site.
AB  - A series of dinitrogen-bridged dimolybdenum-dinitrogen complexes bearing
      metallocene-substituted PNP-pincer ligands is synthesized by the reduction of the
      corresponding monomeric molybdenum-trichloride complexes under 1 atm of molecular
      dinitrogen. Introduction of ferrocene as a redox-active moiety to the pyridine
      ring of the PNP-pincer ligand increases the catalytic activity for the formation
      of ammonia from molecular dinitrogen, up to 45 equiv. of ammonia being formed
      based on the catalyst (22 equiv. of ammonia based on each molybdenum atom of the
      catalyst). The time profile for the catalytic reaction reveals that the presence
      of the ferrocene unit in the catalyst increases the rate of ammonia formation.
      Electrochemical measurement and theoretical studies indicate that an interaction
      between the Fe atom of the ferrocene moiety and the Mo atom in the catalyst may
      play an important role to achieve a high catalytic activity.

PMID- 29218166
TI  - Chemical looping of metal nitride catalysts: low-pressure ammonia synthesis for
      energy storage.
AB  - The activity of many heterogeneous catalysts is limited by strong correlations
      between activation energies and adsorption energies of reaction intermediates.
      Although the reaction is thermodynamically favourable at ambient temperature and
      pressure, the catalytic synthesis of ammonia (NH3), a fertilizer and chemical
      fuel, from N2 and H2 requires some of the most extreme conditions of the chemical
      industry. We demonstrate how ammonia can be produced at ambient pressure from
      air, water, and concentrated sunlight as renewable source of process heat via
      nitrogen reduction with a looped metal nitride, followed by separate
      hydrogenation of the lattice nitrogen into ammonia. Separating ammonia synthesis
      into two reaction steps introduces an additional degree of freedom when designing
      catalysts with desirable activation and adsorption energies. We discuss the
      hydrogenation of alkali and alkaline earth metal nitrides and the reduction of
      transition metal nitrides to outline a promoting role of lattice hydrogen in
      ammonia evolution. This is rationalized via electronic structure calculations
      with the activity of nitrogen vacancies controlling the redox-intercalation of
      hydrogen and the formation and hydrogenation of adsorbed nitrogen species. The
      predicted trends are confirmed experimentally with evolution of 56.3, 80.7, and
      128 MUmol NH3 per mol metal per min at 1 bar and above 550  degrees C via
      reduction of Mn6N2.58 to Mn4N and hydrogenation of Ca3N2 and Sr2N to Ca2NH and
      SrH2, respectively.

PMID- 29218167
TI  - Supramolecular free radicals: near-infrared organic materials with enhanced
      photothermal conversion.
AB  - A novel kind of supramolecular free radical with significantly improved free
      radical yield and enhanced near-infrared (NIR) photothermal conversion has been
      fabricated. Perylene diimide (PDI) can undergo chemical reduction to generate PDI
      radical anions. Cucurbit[7]uril (CB[7]), a bulky hydrophilic head, was utilized
      to encapsulate the two end groups of the PDI derivative via host-guest
      interactions, thus hindering its aggregation and suppressing the dimerization and
      quenching of PDI radical anions in aqueous solution. Due to the increased
      concentration of radical anions and their absorption above 800 nm, the efficiency
      of NIR photothermal conversion was significantly improved. Compared with free
      radicals fabricated by covalent chemistry, the supramolecular free radicals
      established here could provide a facile approach for the promoted formation of
      aromatic free radicals, thus opening up a new strategy for the design of NIR
      photothermal materials with enhanced photothermal conversion.

PMID- 29218168
TI  - Investigating pyridazine and phthalazine exchange in a series of iridium
      complexes in order to define their role in the catalytic transfer of
      magnetisation from para-hydrogen.
AB  - The reaction of [Ir(IMes)(COD)Cl], [IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol
      2-ylidene, COD = 1,5-cyclooctadiene] with pyridazine (pdz) and phthalazine (phth)
      results in the formation of [Ir(COD)(IMes)(pdz)]Cl and [Ir(COD)(IMes)(phth)]Cl.
      These two complexes are shown by nuclear magnetic resonance (NMR) studies to
      undergo a haptotropic shift which interchanges pairs of protons within the bound
      ligands. When these complexes are exposed to hydrogen, they react to form
      [Ir(H)2(COD)(IMes)(pdz)]Cl and [Ir(H)2(COD)(IMes)(phth)]Cl, respectively, which
      ultimately convert to [Ir(H)2(IMes)(pdz)3]Cl and [Ir(H)2(IMes)(phth)3]Cl, as the
      COD is hydrogenated to form cyclooctane. These two dihydride complexes are shown,
      by NMR, to undergo both full N-heterocycle dissociation and a haptotropic shift,
      the rates of which are affected by both steric interactions and free ligand pKa
      values. The use of these complexes as catalysts in the transfer of polarisation
      from para-hydrogen to pyridazine and phthalazine via signal amplification by
      reversible exchange (SABRE) is explored. The possible future use of drugs which
      contain pyridazine and phthalazine motifs as in vivo or clinical magnetic
      resonance imaging probes is demonstrated; a range of NMR and phantom-based MRI
      measurements are reported.

PMID- 29218169
TI  - Steric shielding vs. sigma-pi orbital interactions in triplet-triplet energy
      transfer.
AB  - The influence of non-covalent sigma-pi orbital interactions on triplet-triplet
      energy transfer (TTET) through tuning of the donor excitation energy remains
      basically unexplored. In the present work, we have investigated intermolecular
      TTET using donor moieties covalently linked to a rigid cholesterol (Ch) scaffold.
      For this purpose, diaryl ketones of pi,pi* electronic configuration tethered to
      alpha- or beta-Ch were prepared from tiaprofenic acid (TPA) and suprofen (SUP).
      The obtained systems TPA-alpha-Ch, TPA-beta-Ch, SUP-alpha-Ch and SUP-beta-Ch were
      submitted to photophysical studies (laser flash photolysis and phosphorescence),
      in order to delineate the influence of steric shielding and sigma-pi orbital
      interactions on the rate of TTET to a series of energy acceptors. As a matter of
      fact, fine tuning of the donor triplet energy significantly modifies the rate
      constants of TTET in the absence of diffusion control. The experimental results
      are rationalized by means of theoretical calculations using first principles
      methods based on DFT as well as molecular dynamics.

PMID- 29218170
TI  - Mesoporous 2D covalent organic frameworks based on shape-persistent arylene
      ethynylene macrocycles.
AB  - Macrocycle-to-framework strategy was explored to prepare covalent organic
      frameworks (COFs) using shape-persistent macrocycles as multitopic building
      blocks. We demonstrate well-ordered mesoporous 2D COFs (AEM-COF-1 and AEM-COF-2)
      can be constructed from tritopic arylene-ethynylene macrocycles, which determine
      the topology and modulate the porosity of the materials. According to PXRD
      analysis and computer modelling study, these COFs adopt the fully eclipsed AA
      stacking mode with large accessible pore sizes of 34 or 39 A, which are in good
      agreement with the values calculated by NLDFT modelling of gas adsorption
      isotherms. The pore size of COFs can be effectively expanded by using larger size
      of the macrocycles. Provided a plethora of polygonal shape-persistent macrocycles
      with various size, shape and internal cavity, macrocycle-to-framework strategy
      opens up a promising approach to expand the structural diversity of COFs and
      build hierarchical pore structures within the framework.

PMID- 29218171
TI  - Post-synthetic halide conversion and selective halogen capture in hybrid
      perovskites.
AB  - Reaction with halogen vapor allows us to post-synthetically exchange halides in
      both three- (3D) and two-dimensional (2D) organic-inorganic metal-halide
      perovskites. Films of 3D Pb-I perovskites cleanly convert to films of Pb-Br or Pb
      Cl perovskites upon exposure to Br2 or Cl2 gas, respectively. This gas-solid
      reaction provides a simple method to produce the high-quality Pb-Br or Pb-Cl
      perovskite films required for optoelectronic applications. Reactivity with
      halogens can be extended to the organic layers in 2D metal-halide perovskites.
      Here, terminal alkene groups placed between the inorganic layers can capture Br2
      gas through chemisorption to form dibromoalkanes. This reaction's selectivity for
      Br2 over I2 allows us to scrub Br2 to obtain high-purity I2 gas streams. We also
      observe unusual halogen transfer between the inorganic and organic layers within
      a single perovskite structure. Remarkably, the perovskite's crystallinity is
      retained during these massive structural rearrangements.

PMID- 29218174
TI  - III-defined concepts in chemistry: rigid force constants vs. compliance constants
      as bond strength descriptors for the triple bond in diboryne.
AB  - In a recent publication, the interpretation of Braunschweig's diboryne NHC-BB-NHC
      as a true triple bond is questioned. The analysis by Koppe and Schnockel is
      based, inter alia, on the calculation of rigid coupling force constants.
      Nevertheless, since it is known for a long time that the use of rigid force
      constants as bond strength descriptors is by no means straightforward, we
      recomputed the rigid force constants for a model diboryne, applying different
      coordinate systems and compared the values with the relaxed force constants
      (generalized compliance constants, GCC). In contrast with the results by
      Schnockel and Koppe, the true coupling between the boron-boron bond and the boron
      carbon bond, that is, after the elimination of all numerical artifacts, is
      negligible (fBB/BC = -0.003).

PMID- 29218172
TI  - Enzyme repurposing of a hydrolase as an emergent peroxidase upon metal binding.
AB  - As an alternative to Darwinian evolution relying on catalytic promiscuity, a
      protein may acquire auxiliary function upon metal binding, thus providing it with
      a novel catalytic machinery. Here we show that addition of cupric ions to a 6
      phosphogluconolactonase 6-PGLac bearing a putative metal binding site leads to
      the emergence of peroxidase activity (kcat 7.8 * 10-2 s-1, KM 1.1 * 10-5 M). Both
      X-ray crystallographic and EPR data of the copper-loaded enzyme Cu.6-PGLac reveal
      a bis-histidine coordination site, located within a shallow binding pocket
      capable of accommodating the o-dianisidine substrate.

PMID- 29218173
TI  - Solution structural characterization of an array of nanoscale aqueous inorganic
      Ga13-x In x (0 <= x <= 6) clusters by 1H-NMR and QM computations.
AB  - NMR spectroscopy is the go-to technique for determining the solution structures
      of organic, organometallic, and even macromolecular species. However, structure
      determination of nanoscale aqueous inorganic clusters by NMR spectroscopy remains
      an unexplored territory. The few hydroxo-bridged inorganic species well
      characterized by 1H Nuclear Magnetic Resonance spectroscopy (1H-NMR) do not
      provide enough information for signal assignment and prediction of new samples.
      1H-NMR and quantum mechanical (QM) computations were used to characterize the NMR
      spectra of the entire array of inorganic flat-Ga13-x In x (0 <= x <= 6) nanoscale
      clusters in solution. A brief review of the known signals for MU2-OH and MU3-OH
      bridges gives expected ranges for certain types of protons, but does not give
      enough information for exact peak assignment. Integration values and NOESY data
      were used to assign the peaks of several cluster species with simple 1H-NMR
      spectra. Computations agree with these hydroxide signal assignments and allow for
      assignment of the complex spectra arising from the remaining cluster species.
      This work shows that 1H-NMR spectroscopy provides a variety of information about
      the solution behavior of inorganic species previously thought to be inaccessible
      by NMR due to fast ligand and/or proton exchange in wet solvents.

PMID- 29218175
TI  - The boron-boron triple bond in NHC->B 0000000000000000000000000000000000
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      0000000000000000000000000000000000 B<-NHC.
AB  - Quantum chemical calculations of the compound B2(NHCMe)2 and a thorough
      examination of the electronic structure with an energy decomposition analysis
      provide strong evidence for the appearance of boron-boron triple bond character.
      This holds for the model compound and for the isolated diboryne B2(NHCR)2 of
      Braunschweig which has an even slightly shorter B-B bond. The bonding situation
      in the molecule is best described in terms of NHCMe->B2<-NHCMe donor-acceptor
      interactions and concomitant pi-backdonation NHCMe<-B2->NHCMe which weakens the B
      B bond, but the essential features of a triple bond are preserved. An appropriate
      formula which depicts both interactions is the sketch NHCMe?B
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      0000000000000000000000000000000000 0000000000000000000000000000000000 B?NHCMe.
      Calculations of the stretching force constants FBB which take molecules that have
      genuine single, double and triple bonds as references suggest that the effective
      bond order of B2(NHCMe)2 has the value of 2.34. The suggestion by Koppe and
      Schnockel that the strength of the boron-boron bond in B2(NHCH)2 is only between
      a single and a double bond is repudiated. It misleadingly takes the force
      constant FBB of OBBO as the reference value for a B-B single bond which ignores
      pi bonding contributions. The alleged similarity between the B-O bonds in OBBO
      and the B-C bonds in B2(NHCMe)2 is a mistaken application of the principle of
      isolable relationship.

PMID- 29218176
TI  - Versatile rare earth hexanuclear clusters for the design and synthesis of highly
      connected ftw-MOFs.
AB  - A series of highly porous MOFs were deliberately targeted to contain a 12
      connected rare earth hexanuclear cluster and quadrangular tetracarboxylate
      ligands. The resultant MOFs have an underlying topology of ftw, and are thus
      (4,12)-c ftw-MOFs. This targeted rare earth ftw-MOF platform offers the potential
      to assess the effect of pore functionality and size, via ligand functionalization
      and/or expansion, on the adsorption properties of relevant gases. Examination of
      the gas adsorption properties of these compounds showed that the ftw-MOF-2
      analogues, constructed from rigid ligands with a phenyl, naphthyl, or anthracene
      core exhibited a relatively high degree of porosity. The specific surface areas
      and pore volumes of these analogs are amongst the highest reported for RE-based
      MOFs. Further studies revealed that the Y-ftw-MOF-2 shows promise as a storage
      medium for methane (CH4) at high pressures. Furthermore, Y-ftw-MOF-2 shows
      potential as a separation agent for the selective removal of normal butane (n
      C4H10) and propane (C3H8) from natural gas (NG) as well as interesting properties
      for the selective separation of n-C4H10 from C3H8 or isobutane (iso-C4H10).

PMID- 29218177
TI  - Revealing the thermodynamic driving force for ligand-based reductions in
      quinoids; conceptual rules for designing redox active and non-innocent ligands.
AB  - Metal and ligand-based reductions have been modeled in octahedral ruthenium
      complexes revealing metal-ligand interactions as the profound driving force for
      the redox-active behaviour of orthoquinoid-type ligands. Through an extensive
      investigation of redox-active ligands we revealed the most critical factors that
      facilitate or suppress redox-activity of ligands in metal complexes, from which
      basic rules for designing non-innocent/redox-active ligands can be put forward.
      These rules also allow rational redox-leveling, i.e. the moderation of redox
      potentials of ligand-centred electron transfer processes, potentially leading to
      catalysts with low overpotential in multielectron activation processes.

PMID- 29218178
TI  - Insights into the structure-photoreactivity relationships in well-defined
      perovskite ferroelectric KNbO3 nanowires.
AB  - Structure-function correlations are a central theme in heterogeneous
      (photo)catalysis. In this study, the geometric and electronic structure of
      perovskite ferroelectric KNbO3 nanowires with respective orthorhombic and
      monoclinic polymorphs have been systematically addressed. By virtue of aberration
      corrected scanning transmission electron microscopy, we directly visualize
      surface photocatalytic active sites, measure local atomic displacements at an
      accuracy of several picometers, and quantify ferroelectric polarization combined
      with first-principles calculations. The photoreactivity of the as-prepared KNbO3
      nanowires is assessed toward aqueous rhodamine B degradation under UV light. A
      synergy between the ferroelectric polarization and electronic structure in
      photoreactivity enhancement is uncovered, which accounts for the prominent
      reactivity order: orthorhombic > monoclinic. Additionally, by identifying new
      photocatalytic products, rhodamine B degradation pathways involving N
      deethylation and conjugated structure cleavage are proposed. Our findings not
      only provide new insights into the structure-photoreactivity relationships in
      perovskite ferroelectric photocatalysts, but also have broad implications in
      perovskite-based water splitting and photovoltaics, among others.

PMID- 29218179
TI  - Taming C60 fullerene: tuning intramolecular photoinduced electron transfer
      process with subphthalocyanines.
AB  - Two subphthalocyanine-C60 conjugates have been prepared by means of the 1,3
      dipolar cycloaddition reaction of (perfluoro) or hexa(pentylsulfonyl) electron
      deficient subphthalocyanines to C60. Comprehensive assays regarding the
      electronic features - in the ground and excited state - of the resulting
      conjugates revealed energy and electron transfer processes upon photoexcitation.
      Most important is the unambiguous evidence - in terms of time-resolved
      spectroscopy - of an ultrafast oxidative electron transfer evolving from C60 to
      the photoexcited subphthalocyanines. This is, to the best of our knowledge, the
      first case of an intramolecular oxidation of C60 within electron donor-acceptor
      conjugates by means of only photoexcitation.

PMID- 29218180
TI  - Assessing the exchange coupling in binuclear lanthanide(iii) complexes and the
      slow relaxation of the magnetization in the antiferromagnetically coupled Dy2
      derivative.
AB  - We report here the synthesis and the investigation of the magnetic properties of
      a series of binuclear lanthanide complexes belonging to the metallacrown family.
      The isostructural complexes have a core structure with the general formula
      [Ga4Ln2(shi3-)4(Hshi2-)2(H2shi-)2(C5H5N)4(CH3OH) x (H2O) x ].xC5H5N.xCH3OH.xH2O
      (where H3shi = salicylhydroxamic acid and Ln = GdIII1; TbIII2; DyIII3; ErIII4;
      YIII5; YIII0.9DyIII0.16). Apart from the Er-containing complex, all complexes
      exhibit an antiferromagnetic exchange coupling leading to a diamagnetic ground
      state. Magnetic studies, below 2 K, on a single crystal of 3 using a micro-squid
      array reveal an opening of the magnetic hysteresis cycle at zero field. The
      dynamic susceptibility studies of 3 and of the diluted DyY 6 complexes reveal the
      presence of two relaxation processes for 3 that are due to the excited
      ferromagnetic state and to the uncoupled DyIII ions. The antiferromagnetic
      coupling in 3 was shown to be mainly due to an exchange mechanism, which accounts
      for about 2/3 of the energy gap between the antiferro- and the ferromagnetic
      states. The overlap integrals between the Natural Spin Orbitals (NSOs) of the
      mononuclear fragments, which are related to the magnitude of the
      antiferromagnetic exchange, are one order of magnitude larger for the Dy2 than
      for the Er2 complex.

PMID- 29218181
TI  - Acid/base-regulated reversible electron transfer disproportionation of N-N linked
      bicarbazole and biacridine derivatives.
AB  - Regulation of electron transfer on organic substances by external stimuli is a
      fundamental issue in science and technology, which affects organic materials,
      chemical synthesis, and biological metabolism. Nevertheless, acid/base-responsive
      organic materials that exhibit reversible electron transfer have not been well
      studied and developed, owing to the difficulty in inventing a mechanism to
      associate acid/base stimuli and electron transfer. We discovered a new phenomenon
      in which N-N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives
      undergo electron transfer disproportionation by acid stimulus, forming their
      stable radical cations and reduced species. The reaction occurs through a
      biradical intermediate generated by the acid-triggered N-N bond cleavage reaction
      of BC or TBA, which acts as a two electron acceptor to undergo electron transfer
      reactions with two equivalents of BC or TBA. In addition, in the case of TBA the
      disproportionation reaction is highly reversible through neutralization with
      NEt3, which recovers TBA through back electron transfer and N-N bond formation
      reactions. This highly reversible electron transfer reaction is possible due to
      the association between the acid stimulus and electron transfer via the acid
      regulated N-N bond cleavage/formation reactions which provide an efficient
      switching mechanism, the ability of the organic molecules to act as multi
      electron donors and acceptors, the extraordinary stability of the radical
      species, the highly selective reactivity, and the balance of the redox
      potentials. This discovery provides new design concepts for acid/base-regulated
      organic electron transfer systems, chemical reagents, or organic materials.

PMID- 29218182
TI  - Palladium-catalyzed reductive coupling of phenols with anilines and amines:
      efficient conversion of phenolic lignin model monomers and analogues to
      cyclohexylamines.
AB  - Phenols, being readily available from naturally abundant lignins, are important
      future feedstocks for the renewable production of fuels, chemicals, and energy.
      Herein, a highly efficient Pd-catalyzed direct coupling of phenolic lignin model
      monomers and analogues with anilines to give cyclohexylamines using cheap and
      safe sodium formate as hydrogen donor is described. A variety of secondary and
      tertiary substituted cyclohexylamines can be synthesized under convenient
      conditions in moderate to excellent yields.

PMID- 29218183
TI  - Organocatalytic asymmetric chlorinative dearomatization of naphthols.
AB  - An organocatalytic asymmetric chlorinative dearomatization of naphthols was
      realized for the first time, providing chiral naphthalenones with a Cl-containing
      all-substituted stereocenter in excellent yields and enantioselectivity (up to
      97% yield and 96% ee). The reaction features mild reaction conditions, good
      tolerance of diverse functional groups and simple reaction operation.

PMID- 29218184
TI  - Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic
      carbene as a non-covalent organocatalyst.
AB  - We report the first asymmetric sulfa-Michael addition (SMA) reactions using a
      chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We
      demonstrate that a triazolium salt derived NHC functions as an excellent Bronsted
      base to promote enantioselective carbon-sulfur bond formation. The reaction is
      applicable to a wide range of thiols and electrophilic olefins. Notably,
      quaternary chiral centers bearing both an S atom and a CF3 group were synthesized
      with excellent asymmetric control. Mechanistic studies suggest that the facial
      discrimination is likely to be guided by non-covalent interactions: hydrogen
      bonding and pi-pi stacking.

PMID- 29218185
TI  - pH-responsive and switchable triplex-based DNA hydrogels.
AB  - New methods for the preparation of reversible pH-responsive DNA hydrogels based
      on Hoogsteen triplex structures are described. One system consists of a hydrogel
      composed of duplex DNA units that bridge acrylamide chains at pH = 7.4 and
      undergoes dissolution at pH = 5.0 through the reconfiguration of one of the
      duplex bridging units into a protonated CG.C+ triplex structure. The second
      system consists of a hydrogel consisting of acrylamide chains crosslinked in the
      presence of an auxiliary strand by Hoogsteen TA.T triplex interaction at pH =
      7.0. The hydrogel transforms into a liquid phase at pH = 10.0 due to the
      separation of the triplex bridging units. The two hydrogel systems undergo
      reversible and cyclic hydrogel/solution transitions by subjecting the systems to
      appropriate pH values. The anti-cancer drug, coralyne, binds specifically to the
      TA.T triplex-crosslinked hydrogel thereby increasing its stiffness. The pH
      controlled release of the coralyne from the hydrogel is demonstrated.

PMID- 29218186
TI  - Charge transfer versus molecular conductance: molecular orbital symmetry turns
      quantum interference rules upside down.
AB  - Destructive quantum interference has been shown to strongly reduce charge
      tunneling rates across molecular bridges. The current consensus is that
      destructive quantum interference occurs in cross-conjugated molecules, while
      linearly conjugated molecules exhibit constructive interference. Our experimental
      results on photoinduced charge transfer in donor-bridge-acceptor systems,
      however, show that hole transfer is ten times faster through a cross-conjugated
      biphenyl bridge than through a linearly conjugated biphenyl bridge. Electronic
      structure calculations reveal that the surprisingly low hole transfer rate across
      the linearly conjugated biphenyl bridge is caused by the presence of destructive
      instead of constructive interference. We find that the specific molecular orbital
      symmetry of the involved donor and acceptor states leads to interference
      conditions that are different from those valid in single molecule conduction
      experiments. Furthermore, the results indicate that by utilizing molecular
      orbital symmetry in a smart way new opportunities of engineering charge transfer
      emerge.

PMID- 29218187
TI  - Vermicious thermo-responsive Pickering emulsifiers.
AB  - Thermo-responsive vermicious (or worm-like) diblock copolymer nanoparticles
      prepared directly in n-dodecane via polymerisation-induced self-assembly (PISA)
      were used to stabilise water-in-oil Pickering emulsions. Mean droplet diameters
      could be tuned from 8 to 117 MUm by varying the worm copolymer concentration and
      the water volume fraction and very high worm adsorption efficiencies (~100%)
      could be obtained below a certain critical copolymer concentration (~0.50%).
      Heating a worm dispersion up to 150  degrees C led to a worm-to-sphere
      transition, which proved to be irreversible if conducted at sufficiently low
      copolymer concentration. This affords a rare opportunity to directly compare the
      Pickering emulsifier performance of chemically identical worms and spheres. It is
      found that the former nanoparticles are markedly more efficient, since worm
      stabilised water droplets are always smaller than the equivalent sphere
      stabilised droplets prepared under identical conditions. Moreover, the latter
      emulsions are appreciably flocculated, whereas the former emulsions proved to be
      stable. SAXS studies indicate that the mean thickness of the adsorbed worm layer
      surrounding the water droplets is comparable to that of the worm cross-section
      diameter determined for non-adsorbed worms dispersed in the continuous phase.
      Thus the adsorbed worms form a monolayer shell around the water droplets, rather
      than ill-defined multilayers. Under certain conditions, demulsification occurs on
      heating as a result of a partial worm-to-sphere morphological transition.

PMID- 29218188
TI  - The Abeta40 and Abeta42 peptides self-assemble into separate homomolecular
      fibrils in binary mixtures but cross-react during primary nucleation.
AB  - The assembly of proteins into amyloid fibrils, a phenomenon central to several
      currently incurable human diseases, is a process of high specificity that
      commonly tolerates only a low level of sequence mismatch in the component
      polypeptides. However, in many cases aggregation-prone polypeptides exist as
      mixtures with variations in sequence length or post-translational modifications;
      in particular amyloid beta (Abeta) peptides of variable length coexist in the
      central nervous system and possess a propensity to aggregate in Alzheimer's
      disease and related dementias. Here we have probed the co-aggregation and cross
      seeding behavior of the two principal forms of Abeta, Abeta40 and Abeta42 that
      differ by two hydrophobic residues at the C-terminus. We find, using isotope
      labeling, mass spectrometry and electron microscopy that they separate
      preferentially into homomolecular pure Abeta42 and Abeta40 structures during
      fibril formation from mixed solutions of both peptides. Although mixed fibrils
      are not formed, the kinetics of amyloid formation of one peptide is affected by
      the presence of the other form. In particular monomeric Abeta42 accelerates
      strongly the aggregation of Abeta40 in a concentration-dependent manner. Whereas
      the aggregation of each peptide is catalyzed by low concentrations of preformed
      fibrils of the same peptide, we observe a comparably insignificant effect when
      Abeta42 fibrils are added to Abeta40 monomer or vice versa. Therefore we conclude
      that fibril-catalysed nucleus formation and elongation are highly sequence
      specific events but Abeta40 and Abeta42 interact during primary nucleation. These
      results provide a molecular level description of homomolecular and
      heteromolecular aggregation steps in mixtures of polypeptide sequence variants.

PMID- 29218189
TI  - A pH-responsive soluble polymer-based homogeneous system for fast and highly
      efficient N-glycoprotein/glycopeptide enrichment and identification by mass
      spectrometry.
AB  - Liquid phase homogeneous reactions using soluble polymer supports have found
      numerous applications in homogeneous catalysis and organic synthesis because of
      their advantages of no interface mass transfer limitation and a high conversion
      rate. However, their application in analytical separation is limited by the
      inefficient/inconvenient recovery of the target molecules from the extremely
      complex biological samples. Here, we report a stimuli-responsive polymer system
      for facile and efficient enrichment of trace amounts of biomolecules from complex
      biological samples. The soluble polymer supports provide a homogeneous reaction
      system with fast mass transfer and facilitate interactions between the supports
      and the target molecules. More importantly, the stimuli-responsive polymers
      exhibit reversible self-assembly and phase separation under pH variations, which
      leads to facial sample recovery with a high yield of the target biomolecules. The
      stimuli-responsive polymer is successfully applied to the enrichment of low
      abundant N-glycoproteins/glycopeptides, which play crucial roles in various key
      biological processes in mammals and are closely correlated with the occurrence,
      progression and metastasis of cancer. N-Glycoprotein is coupled to the stimuli
      responsive polymer using the reported hydrazide chemistry with pre-oxidation of
      the oligosaccharide structure. Highly efficient enrichment of N-glycoproteins/N
      glycopeptides with >95% conversion rate is achieved within 1 h, which is eight
      times faster than using solid/insoluble hydrazide enrichment materials. Mass
      spectrometry analysis achieves low femtomolar identification sensitivity and
      obtained 1317 N-glycopeptides corresponding to 458 N-glycoproteins in mouse
      brain, which is more than twice the amount obtained after enrichment using
      commercial solid/insoluble materials. These results demonstrate the capability of
      this "smart" polymer system to combine stimuli-responsive and target-enrichment
      moieties to achieve improved identification of key biological and disease related
      biomolecules.

PMID- 29218190
TI  - Diastereodivergent organocatalysis for the asymmetric synthesis of chiral
      annulated furans.
AB  - Disclosed herein is a stereoselective method for the synthesis of 2,3-furan fused
      carbocycles bearing adjacent quaternary and tertiary carbon stereocenters. The
      chemistry is based on an asymmetric addition of beta-ketoesters to 2-(1-alkynyl)
      2-alkene-1-ones catalysed by natural cinchona alkaloids followed by a silver
      catalysed intramolecular cycloisomerisation. By exploiting the distinct catalysis
      modes of quinine, which can act either as a general base or, upon opportune
      modifications, as a phase transfer catalyst, a complete switch of the enforced
      sense of diastereoinduction is achieved. The stereodivergent systems enable
      access to the full matrix of all possible stereoisomeric products.

PMID- 29218191
TI  - Microdialysis SPR: diffusion-gated sensing in blood.
AB  - Chemical measurements are rarely performed in crude blood due to the poor
      performance of sensors and devices exposed to biofluids. In particular,
      biosensors have been severely limited for detection in whole blood due to surface
      fouling from proteins, the interaction of cells with the sensor surface and
      potential optical interference when considering optical methods of analysis. To
      solve this problem, a dialysis chamber was introduced to a surface plasmon
      resonance (SPR) biosensor to create a diffusion gate for large molecules. This
      dialysis chamber relies on the faster migration of small molecules through a
      microporous membrane towards a sensor, located at a specified distance from the
      membrane. Size filtering and diffusion through a microporous membrane restricted
      the access of blood cells and larger biomolecules to a sensing chamber, while
      smaller, faster diffusing biomolecules migrated preferentially to the sensor with
      limited interference from blood and serum. The affinity of a small peptide
      (DBG178) with anti-atherosclerotic activity and targeting type B scavenger
      receptor CD36 was successfully monitored at micromolar concentrations in human
      serum and blood without any pre-treatment of the sample. This concept could be
      generally applied to a variety of targets for biomolecular interaction monitoring
      and quantification directly in whole blood, and could find potential applications
      in biochemical assays, pharmacokinetic drug studies, disease treatment
      monitoring, implantable plasmonic sensors, and point-of-care diagnostics.

PMID- 29218192
TI  - Consecutive C-F bond activation and C-F bond formation of heteroaromatics at
      rhodium: the peculiar role of FSi(OEt)3.
AB  - C-F activation of 2,3,5,6-tetrafluoropyridine at [Rh{Si(OEt)3}(PEt3)3] (1) yields
      [Rh{2-(3,5,6-C5F3HN)}(PEt3)3] (2) and FSi(OEt)3, but in an unprecedented
      consecutive reaction FSi(OEt)3 acts as a fluoride source to give [Rh(4
      C5F4N)(PEt3)3] (4) by regeneration of the C-F bond and C-H activation. Analogous
      refluorination steps were observed for other 2-pyridyl rhodium complexes. NMR
      spectroscopic studies revealed a delicate balance between the feasibility for C-F
      bond formation accompanied by a C-H activation and the occurrence of competing
      reactions such as hydrodefluorinations induced by the intermediary presence of
      H2.

PMID- 29218193
TI  - Hyperpolarization of amino acid derivatives in water for biological applications.
AB  - We report on the successful synthesis and hyperpolarization of N-unprotected
      alpha-amino acid ethyl propionate esters and extensively, on an alanine
      derivative hyperpolarized by PHIP (4.4 +/- 1.0% 13C-polarization), meeting
      required levels for in vivo detection. Using water as solvent increases
      biocompatibility and the absence of N-protection is expected to maintain
      biological activity.

PMID- 29218194
TI  - Strong circularly polarized luminescence from the supramolecular gels of an
      achiral gelator: tunable intensity and handedness.
AB  - Although the importance of circularly polarized luminescence (CPL) materials has
      been widely recognized, the CPL responses of supramolecular gels are still rarely
      studied. Moreover, developing CPL materials based on supramolecular gels is of
      great significance, due to their special advantages and important applications.
      Herein, we report the first circularly polarized supramolecular gels self
      assembled exclusively from a simple achiral C3-symmetric molecule. Most
      importantly, the excellent tunability of these novel CPL materials, which
      benefits from achiral molecular building blocks as well as the nature of
      supramolecular gels, has been investigated. Thus, the CPL intensity of these
      supramolecular gels is easily enhanced by mechanical stirring or doping chiral
      amines. The handedness of CPL signals is controlled by the chirality of organic
      amines.

PMID- 29218195
TI  - Enantioselective annulation of enals with 2-naphthols by triazolium salts derived
      from l-phenylalanine.
AB  - A series of chiral triazolium salts have been synthesized from methyl l
      phenylalaninate hydrochloride. The NHCs derived from this class of novel
      triazolium salts were found to be highly efficient catalysts in the annulation
      reaction of enals and 2-naphthols. These reactions proceeded with high
      chemoselectivity and wide substrate scope affording enantioenriched beta
      arylsplitomicins in good yields with up to 96% ee.

PMID- 29218196
TI  - Copper-catalyzed diamination of unactivated alkenes with hydroxylamines.
AB  - A copper-catalyzed regio- and stereoselective diamination of unactivated alkenes
      has been developed with O-acylhydroxylamines as electrophilic nitrogen sources
      and oxidants. This method provides the first example of metal-catalyzed alkene
      diamination for directly installing an electron-rich amino group and extends the
      diamination scope for the synthesis of diverse 1,2-diamines. It offers a rapid
      and efficient approach to construct a wide range of 1,2-diamines that are an
      important structural motif in organic synthesis, medicines, catalysts and
      ligands.

PMID- 29218198
TI  - Iron catalyzed CO2 hydrogenation to formate enhanced by Lewis acid co-catalysts.
AB  - A family of iron(ii) carbonyl hydride complexes supported by either a
      bifunctional PNP ligand containing a secondary amine, or a PNP ligand with a
      tertiary amine that prevents metal-ligand cooperativity, were found to promote
      the catalytic hydrogenation of CO2 to formate in the presence of Bronsted base.
      In both cases a remarkable enhancement in catalytic activity was observed upon
      the addition of Lewis acid (LA) co-catalysts. For the secondary amine supported
      system, turnover numbers of approximately 9000 for formate production were
      achieved, while for catalysts supported by the tertiary amine ligand, nearly 60
      000 turnovers were observed; the highest activity reported for an earth abundant
      catalyst to date. The LA co-catalysts raise the turnover number by more than an
      order of magnitude in each case. In the secondary amine system, mechanistic
      investigations implicated the LA in disrupting an intramolecular hydrogen bond
      between the PNP ligand N-H moiety and the carbonyl oxygen of a formate ligand in
      the catalytic resting state. This destabilization of the iron-bound formate
      accelerates product extrusion, the rate-limiting step in catalysis. In systems
      supported by ligands with the tertiary amine, it was demonstrated that the LA
      enhancement originates from cation assisted substitution of formate for
      dihydrogen during the slow step in catalysis.

PMID- 29218197
TI  - Luminescence switch-on detection of protein tyrosine kinase-7 using a G
      quadruplex-selective probe.
AB  - A series of luminescent iridium(iii) complexes were synthesised and evaluated for
      their ability to act as luminescent G-quadruplex-selective probes. The
      iridium(iii) complex 9 [Ir(pbi)2(5,5-dmbpy)]PF6 (where pbi = 2-phenyl-1H
      benzo[d]imidazole; 5,5-dmbpy = 5,5'-dimethyl-2,2'-bipyridine) exhibited high
      luminescence for G-quadruplex DNA compared to dsDNA and ssDNA, and was employed
      to construct a G-quadruplex-based assay for protein tyrosine kinase-7 (PTK7) in
      aqueous solution. PTK7 is an important biomarker for a range of leukemias and
      solid tumors. In the presence of PTK7, the specific binding of the sgc8 aptamer
      sequence triggers a structural transition and releases the G-quadruplex-forming
      sequence. The formation of the nascent G-quadruplex structure is then detected by
      the G-quadruplex-selective iridium(iii) complex with an enhanced luminescent
      response. Moreover, the application of the assay for detecting PTK7 in cellular
      debris and membrane protein extract was demonstrated. To our knowledge, this is
      the first G-quadruplex-based assay for PTK7.

PMID- 29218199
TI  - Homochiral self-assembly of biocoordination polymers: anion-triggered helicity
      and absolute configuration inversion.
AB  - The different natures of the weakly coordinating anions - triflate or perchlorate
      - in the Cu2+-mediated self-assembly of cytidine monophosphate nucleotide play a
      fundamental role in the homochiral resolution process, yielding one-dimensional
      copper(ii) coordination polymers of opposite helicity that can be easily
      inverted, in a reversible way, by changing the nature of the anion as revealed by
      circular dichroism experiments both in solution and in the solid state.

PMID- 29218200
TI  - Low temperature ionic conductor: ionic liquid incorporated within a metal-organic
      framework.
AB  - Ionic liquids (ILs) show promise as safe electrolytes for electrochemical
      devices. However, the conductivity of ILs decreases markedly at low temperatures
      because of strong interactions arising between the component ions. Metal-organic
      frameworks (MOFs) are appropriate microporous host materials that can control the
      dynamics of ILs via the nanosizing of ILs and tunable interactions of MOFs with
      the guest ILs. Here, for the first time, we report on the ionic conductivity of
      an IL incorporated within a MOF. The system studied consisted of EMI-TFSA (1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide) and ZIF-8
      (Zn(MeIM)2, H(MeIM) = 2-methylimidazole) as the IL and the MOF, respectively.
      While the ionic conductivity of bulk EMI-TFSA showed a sharp decrease arising
      from freezing, the EMI-TFSA@ZIF-8 showed no marked decrease because there was no
      phase transition. The ionic conductivity of EMI-TFSA@ZIF-8 was higher than that
      of bulk EMI-TFSA below 250 K. This result points towards a novel method by which
      to design electrolytes for electrochemical devices such as batteries that can
      operate at low temperatures.

PMID- 29218201
TI  - Simple electrochemical sensing of attomolar proteins using fabricated complexes
      with enhanced surface binding avidity.
AB  - Various strategies have been proposed for the detection of disease protein
      biomarkers; however, most methods are too expensive, cumbersome or limited in
      sensitivity for clinical use. Here, we report that a fabricated complex can be
      used as a powerful tool to detect trace proteins in complex samples. In this
      strategy, a DNA-protein complex that comprises of one target molecule and two or
      more deoxyribozyme-containing probes can exhibit autonomous cleavage behavior on
      the surface of the substrate DNA modified electrode. In the meantime, the complex
      can remove the cleaved DNA fragment from the electrode surface by taking
      advantage of the proximity effect. The proposed approach allows one-step and
      highly sensitive detection of a variety of targets based on the changes of the
      direct electrochemical readout. Moreover, this method may also have considerable
      advantages over the commonly reported DNA amplification-assisted immunoassays,
      particularly in terms of assay simplicity and cost, which may hold great
      potential for application in resource-constrained regions.

PMID- 29218202
TI  - Target-driven DNA association to initiate cyclic assembly of hairpins for
      biosensing and logic gate operation.
AB  - A target-driven DNA association was designed to initiate cyclic assembly of
      hairpins, which led to an enzyme-free amplification strategy for detection of a
      nucleic acid or aptamer substrate and flexible construction of logic gates. The
      cyclic system contained two ssDNA (S1 and S2) and two hairpins (H1 and H2). These
      ssDNA could co-recognize the target to produce an S1-target-S2 structure, which
      brought their toehold and branch-migration domains into close proximity to
      initiate the cyclic assembly of hairpins. The assembly product further induced
      the dissociation of a double-stranded probe DNA (Q:F) via toehold-mediated strand
      displacement to switch the fluorescence signal. This method could detect DNA and
      ATP as model analytes down to 21.6 pM and 38 nM, respectively. By designing
      different DNA input strands, the "AND", "INHIBIT" and "NAND" logic gates could be
      activated to achieve the output signal. The proposed biosensing and logic gate
      operation platform showed potential applications in disease diagnosis.

PMID- 29218203
TI  - Mechanism of the cooperative Si-H bond activation at Ru-S bonds.
AB  - The nature of the hydrosilane activation mediated by ruthenium(ii) thiolate
      complexes of type [(R3P)Ru(SDmp)]+[BArF4]- is elucidated by an in-depth
      experimental and theoretical study. The combination of various ruthenium(ii)
      thiolate complexes and tertiary hydrosilanes under variation of the phosphine
      ligand and the substitution pattern at the silicon atom is investigated,
      providing detailed insight into the activation mode. The mechanism of action
      involves reversible heterolytic splitting of the Si-H bond across the polar Ru-S
      bond without changing the oxidation state of the metal, generating a
      ruthenium(ii) hydride and sulfur-stabilized silicon cations, i.e.
      metallasilylsulfonium ions. These stable yet highly reactive adducts, which serve
      as potent silicon electrophiles in various catalytic transformations, are fully
      characterized by systematic multinuclear NMR spectroscopy. The structural
      assignment is further verified by successful isolation and crystallographic
      characterization of these key intermediates. Quantum-chemical analyses of diverse
      bonding scenarios are in excellent agreement with the experimental findings.
      Moreover, the calculations reveal that formation of the hydrosilane adducts
      proceeds via barrierless electrophilic activation of the hydrosilane by
      sterically controlled eta1 (end-on) or eta2 (side-on) coordination of the Si-H
      bond to the Lewis acidic metal center, followed by heterolytic cleavage of the Si
      H bond through a concerted four-membered transition state. The Ru-S bond remains
      virtually intact during the Si-H bond activation event and also preserves
      appreciable bonding character in the hydrosilane adducts. The overall Si-H bond
      activation process is exergonic with DeltaG0r ranging from -20 to -40 kJ mol-1,
      proceeding instantly already at low temperatures.

PMID- 29218204
TI  - A structural remedy toward bright dipolar fluorophores in aqueous media.
AB  - The donor-acceptor (D-A) type dipolar fluorophores, an important class of
      luminescent dyes with two-photon absorption behaviour, generally emit strongly in
      organic solvents but poorly in aqueous media. To understand and enhance the poor
      emission behaviour of dipolar dyes in aqueous media, we undertake a rational
      approach that includes a systematic structure variation of the donor, amino
      substituent of acedan, an important two-photon dye. We identify several factors
      that influence the emission behaviour of the dipolar dyes in aqueous media
      through computational and photophysical studies on new acedan derivatives. As a
      result, we can make acedan dyes emit bright fluorescence under one- and two
      photon excitation in aqueous media by suppressing the liable factors for poor
      emission: 1,3-allylic strain, rotational freedom, and hydrogen bonding with
      water. We also validate that these findings can be generally extended to other
      dipolar fluorophores, as demonstrated for naphthalimide, coumarin and (4-nitro
      2,1,3-benzoxadiazol-7-yl)amine (NBD) dyes. The new acedan and naphthalimide dyes
      thus allow us to obtain much brighter two-photon fluorescent images in cells and
      tissues than in their conventional forms. As an application of these findings, a
      thiol probe is synthesized based on a new naphthalimide dye, which shows greatly
      enhanced fluorescence from the widely used N,N-dimethyl analogue. The results
      disclosed here provide essential guidelines for the development of efficient
      dipolar dyes and fluorescence probes for studying biological systems,
      particularly by two-photon microscopy.

PMID- 29218205
TI  - ATP-triggered biomimetic deformations of bioinspired receptor-containing polymer
      assemblies.
AB  - Designing synthetic polymer assemblies that can sense a biological signal to
      mimic cell activities is elusive. We develop a class of block copolymer
      containing bioinspired host units as supramolecular catchers for the highly
      selective capture of adenosine-5'-triphosphate (ATP). Driven by ATP, these block
      copolymers undergo a stepwise self-assembly and exhibit cascading deformation
      into highly-ordered nanostructures via the specific recognition effect between
      ATP and the receptor. By modulating the ATP concentration, one can precisely
      control the biomimetic evolution of these assemblies in diverse dimensionalities
      and geometries, like certain organellar deformations. Moreover, the ATP/polymer
      hybrid aggregates can be reversibly disassembled in response to phosphatase. The
      special ability of the artificial assemblies to sense intracellular bioactivators
      can offer new insight into bio-responsive nanomaterials for cellular
      applications.

PMID- 29218206
TI  - Synthesis of open-mouthed, yolk-shell Au@AgPd nanoparticles with access to
      interior surfaces for enhanced electrocatalysis.
AB  - We have successfully produced open-mouthed, yolk-shell (OM-YS) Au@AgPd
      nanoparticles (NPs) via galvanic replacement reaction at room temperature; each
      NP has a large opening on its AgPd shells. Owing to the openings on the AgPd
      shells, the inner surfaces of the AgPd shells of as-prepared OM-YS Au@AgPd NPs
      become accessible to the surrounding media. These new structural characters make
      the present OM-YS Au@AgPd NPs excellent catalysts for electrochemical oxidation
      of ethanol in alkaline media. Their electrochemical active surface area is 87.8
      m2 g-1 and the mass activity is 1.25 A mgPd-1. Moreover, the openings on the AgPd
      shells also make the surfaces of the Au cores in OM-YS Au@AgPd NPs accessible to
      the reaction media, which significantly facilitates the removal of CO and other
      carbonaceous intermediate species, thus leading to substantially enhanced
      durability and stability. This superior electrocatalytic performance cannot be
      implemented by using conventional YS Au@AgPd NPs or commercially available Pd/C
      catalysts.

PMID- 29218207
TI  - How important are dispersion interactions to the strength of aromatic stacking
      interactions in solution?
AB  - In this study, the contributions of London dispersion forces to the strength of
      aromatic stacking interactions in solution were experimentally assessed using a
      small molecule model system. A series of molecular torsion balances were designed
      to measure an intramolecular stacking interaction via a conformational
      equilibrium. To probe the importance of the dispersion term, the size and
      polarizability of one of the aromatic surfaces were systematically increased
      (benzene, naphthalene, phenanthrene, biphenyl, diphenylethene, and
      diphenylacetylene). After correcting for solvophobic, linker, and electrostatic
      substituent effects, the variations due to polarizability were found to be an
      order of magnitude smaller in solution than in comparison to analogous
      computational studies in vacuo. These results suggest that in solution the
      dispersion term is a small component of the aromatic stacking interaction in
      contrast to their dominant role in vacuo.

PMID- 29218209
TI  - Anomalous origin of the right colic artery from the right gastroepiploic artery
      during complete mesocolic excision: a rare case report.
AB  - Complete mesocolic excision (CME) is a standardized surgical procedure for
      colonic cancer that requires ample knowledge of the anatomical patterns of the
      colic arteries. Variations of the colic vessels encumber both surgical and
      endovascular techniques. In the presented case below, the right colic artery was
      incidentally detected emerging from the right gastroepiploic artery, during CME.
      Surgeons should be always aware of this variation in order to perform safe
      abdominal surgeries and sufficient resection of the regional lymph nodes with a
      view to minimizing the probability of recurrence of disease when encountering
      colonic cancer.

PMID- 29218208
TI  - Rapid access to phospholipid analogs using thiol-yne chemistry.
AB  - Phospholipids and glycolipids constitute an essential part of biological
      membranes, and are of tremendous fundamental and practical interest.
      Unfortunately, the preparation of functional phospholipids, or synthetic analogs,
      is often synthetically challenging. Here we utilize thiol-yne click chemistry
      methodology to gain access to phospho- and glycolipid analogs. Alkynyl
      hydrophilic head groups readily photoreact with numerous thiol modified lipid
      tails to yield the appropriate dithioether phospho- or glycolipids. The resulting
      structures closely resemble the structure and function of native
      diacylglycerolipids. Dithioether phosphatidylcholines (PCs) are suitable for
      forming giant unilamellar vesicles (GUV), which can be used as vessels for cell
      free expression systems. The unnatural thioether linkages render the lipids
      resistant to phospholipase A2 hydrolysis. We utilize the improved stability of
      these lipids to control the shrinkage of GUVs composed of a mixture of 1,2
      dioleoyl-sn-glycero-3-phosphocholine (DOPC) and dioleyl-dithioether PC,
      concentrating encapsulated nanoparticles. We imagine that these readily
      accessible lipids could find a number of applications as natural lipid
      substitutes.

PMID- 29218210
TI  - Primary hydatid disease of the axilla presenting as a cystic mass.
AB  - Hydatid cysts is most often characterized by hepatic and pulmonary involvement,
      but it also rarely involves other body parts and systems. Axillary involvement by
      hydatid cysts is considerably rare in countries with endemic hydatid cyst
      manifestation, and cases from countries like Turkey are still widely reported. A
      young woman aged 24 years was seen at our clinic for a painful axillary mass. She
      was detected by a thoracoabdominal tomographic examination to have a localized
      multilocular cystic mass in her left axillary region; the mass showed little soft
      tissue invasion at its periphery but no hepatic or pulmonary involvement at all.
      It was excised from its stalks and totally removed. The diagnosis of hydatid cyst
      was made by macroscopic and microscopic examination. It was highlighted by this
      case report that the differential diagnosis of palpable masses in axillary region
      should include hydatid cyst, particularly in areas where the disease is endemic.

PMID- 29218211
TI  - A rare anatomical variant: transosseous supraclavicular nerve identified during
      clavicle fracture fixation.
AB  - We describe a rare case of an anatomical variant of the supraclavicular nerve in
      the intra-operative setting of clavicle fixation for a fracture. Intra
      operatively it was noted that one of the supraclavicular nerves was passing
      through a foramen in the clavicle shaft. A 60-year-old gentleman presented with a
      displaced multifragmentary fracture of the left clavicle after a fall. Plate
      fixation with a pre-contoured locking plate was performed under general
      anaesthesia. The clavicle was exposed through an infraclavicular transverse
      incision. It was necessary to divide this transosseous nerve branch to permit
      appropriate plate positioning. Post-operatively the patient was left with some
      incisional chest numbness. Surgeons should aim to preserve the branches of the
      supraclavicular nerve although this may not always be possible as we have
      demonstrated. The patient should be warned about potential deficit.

PMID- 29218212
TI  - Heads up Descemet membrane endothelial keratoplasty performed using a 3D
      visualization system.
AB  - A 68-year-old female underwent Descemet membrane endothelial keratoplasty (DMEK)
      in her right eye using a 3D visualization system with the surgeon looking
      directly to a digital screen instead of through the eyepieces of the surgical
      microscope. The procedure was uneventful. Five weeks after the surgery the DMEK
      graft was in good position and totally adhered, the cornea clear and uncorrected
      distance visual acuity 20/50. This is the first reported case of DMEK using 3D
      augmented reality visualization system. It seems to offer advantages for the
      corneal surgeon in critical steps of the endothelial grafting procedure.

PMID- 29218213
TI  - Two cases of somatic-type malignancy as a very late relapse of testicular cancer
      successfully managed by surgical resection.
AB  - A late-relapse germ cell tumor might contain malignant non-germ cell tumors,
      known as 'somatic-type malignancy (SM)'. The development of a secondary SM is
      rare, and this phenomenon remains poorly understood. Case 1 developed lung
      metastasis 13 years after chemotherapy followed by retroperitoneal lymph node
      dissection for stage IIA non-seminoma. The tumor increased in size after
      chemotherapy. The patient underwent a pneumonectomy. Pathology revealed an
      adenocarcinoma with immature teratoma. The patient has experienced no relapse for
      9 years. Case 2 developed a pelvic tumor after 10 years of surveillance for stage
      I seminoma. The tumor increased in size after chemotherapy. The patient underwent
      pelvic tumor resection with cystectomy. Pathology revealed a mature teratoma with
      SMs consisting of sarcoma and adenocarcinoma. The patient has experienced no
      relapse for 6 months. Surgical resection played a major role in the treatment of
      very late-relapse germ cell tumors with SM.

PMID- 29218214
TI  - Use of botulinum A toxin for proctalgia fugax-a case report of successful
      treatment.
AB  - Proctalgia fugax is considered as intermittent anal pain of unknown etiology; a
      variety of treatments have been used, without, however, permanent results.
      Injection of botulinum A toxin is recently suggested as an alternative option. We
      present the case of a woman presenting proctalgia fugax that was untreatable
      through other current forms of treatment. After two administrations of botulinum
      A toxin, 80 units and 100 units each, the patient remained asymptomatic on 8
      month follow-up control. Botulinum A toxin injection can reduce internal anal
      sphincter pressure, leading to relief of symptoms, and seems a promising option
      with minimal morbidity in cases on proctalgia fugax that does not respond to
      other current treatments.

PMID- 29218215
TI  - Leiomyoma of round ligament mimicking an incarcerated inguinal hernia-report of a
      rare case.
AB  - Inguinal hernia is a common condition and may contain small or large bowel,
      omentum or other tissues. Leiomyomas of a round ligament are a rare condition
      occurring predominantly in premenopausal women. Abdominal, inguinal and vulvar
      locations have been described. Rare situations have been reported in which
      leiomyomas resemble to an incarcerated inguinal hernia. We describe a rare case
      of a leiomyoma of a round ligament in a young Caucasian female mimicking an
      incarcerated inguinal hernia. The treatment was surgical and we were able to
      remove the leiomyoma of the round ligament successfully. Leiomyoma of the round
      ligament is a benign tumor. Surgeons should take into consideration this
      condition in terms of differential diagnosis of masses that mimic an inguinal
      hernia.

PMID- 29218216
TI  - Primary low-grade endometrial stromal sarcoma arising in the vagina: report of an
      unusual case and literature review.
AB  - Endometrial stromal sarcoma rarely occurs as an extrauterine neoplasm and it is
      even more unlikely to be found in the vagina. To the best of our knowledge, only
      six cases of primary vaginal endometrial stromal sarcoma without association with
      endometriosis have been published to this day. We describe a case of a 58-year
      old female with a history of vaginal heaviness caused by a mass lesion. After a
      biopsy was taken, the histopathological findings and immunohistochemical stains
      were consistent with low-grade endometrial stromal sarcoma. The patient underwent
      total hysterectomy and bilateral salpingo-oophorectomy with lymph node dissection
      followed by hormonal therapy. This line of management was heavily based on the
      treatment guidelines for endometrial stromal sarcoma.

PMID- 29218217
TI  - Gastric band tubing-related complication during pregnancy.
AB  - In the past few decades, laparoscopic adjustable gastric banding is one of the
      most common bariatric procedures performed to treat morbid obesity. Device
      related complication such as connection-tubing problem is rare. Here we present a
      case of gastric band tubing complication during pregnancy. This case illustrates
      the need to maintain high index of suspicion of gastric band device-related
      complication during pregnancy and early referral for bariatric surgical
      assessment is recommended.

PMID- 28435665
TI  - A voltage-dependent fluorescent indicator for optogenetic applications,
      archaerhodopsin-3: Structure and optical properties from in silico modeling.
AB  - It was demonstrated in recent studies that some rhodopsins can be used in
      optogenetics as fluorescent indicators of membrane voltage. One of the promising
      candidates for these applications is archaerhodopsin-3. While it has already
      shown encouraging results, there is still a large room for improvement. One of
      possible directions is increasing the intensity of the protein's fluorescent
      signal. Rational design of mutants with an improved signal is an important task,
      which requires both experimental and theoretical studies. Herein, we used a
      homology-based computational approach to predict the three-dimensional structure
      of archaerhodopsin-3, and a Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid
      approach with high-level multireference ab initio methodology (SORCI+Q/AMBER) to
      model optical properties of this protein. We demonstrated that this methodology
      allows for reliable prediction of structure and spectral properties of
      archaerhodopsin-3. The results of this study can be utilized for computational
      molecular design of efficient fluorescent indicators of membrane voltage for
      modern optogenetics on the basis of archaerhodopsin-3.

PMID- 29152220
TI  - Preference and willingness to pay for nutritional counseling services in urban
      Hanoi.
AB  - Background: Despite substantial achievement in reducing malnutrition rates in
      Vietnam, there has been an increasing rate of overweight individuals in urban
      areas, which may result in a high burden of non-communicable diseases.
      Nutritional counseling clinics have been introduced in several settings; however,
      little is known about the preference for this service among urban clients. This
      study aimed to assess the preference and willingness to pay (WTP) for nutritional
      counseling services among urban clients. Methods: We interviewed 429 clients who
      attended Hanoi Medical University Nutritional Counseling Clinic (Hanoi, Vietnam).
      WTP was determined using double-bounded dichotomous-choice questions and open
      ended questions. Results: In total, 78.6% respondents were willing to use
      nutritional counseling services. The mean amount of WTP for one-time service and
      one-year package was 96,100VND (~$4.3) and 946,400VND (~$41.9), respectively.
      Clients' willingness to use the service was higher among females, those seeking
      counseling for elderly people and those who preferred face-to-face counseling
      services (p<0.05). WTP was higher among those who were over 35 years old, those
      seeking services for the elderly people, those having poor nutritional status,
      and those having under-6 year old children (p<0.05). Conclusions: The preference
      and WTP for nutritional counseling services in urban Hanoi were relatively high.
      Scaling up this service is necessary to actively prevent and control the spread
      of non-communicable diseases.

PMID- 28529710
TI  - Introducing the Brassica Information Portal: Towards integrating genotypic and
      phenotypic Brassica crop data.
AB  - The Brassica Information Portal (BIP) is a centralised repository for brassica
      phenotypic data. The site hosts trait data associated with brassica research and
      breeding experiments conducted on brassica crops, that are used as oilseeds,
      vegetables, livestock forage and fodder and for biofuels. A key feature is the
      explicit management of meta-data describing the provenance and relationships
      between experimental plant materials, as well as trial design and trait
      descriptors. BIP is an open access and open source project, built on the schema
      of CropStoreDB, and as such can provide trait data management strategies for any
      crop data. A new user interface and programmatic submission/retrieval system
      helps to simplify data access for researchers, breeders and other end-users. BIP
      opens up the opportunity to apply integrative, cross-project analyses to data
      generated by the Brassica Research Community. Here, we present a short
      description of the current status of the repository.

PMID- 29218223
TI  - Additive effects of pCO2 and temperature on respiration rates of the Antarctic
      pteropod Limacina helicina antarctica.
AB  - The Antarctic pteropod, Limacina helicina antarctica, is a dominant member of the
      zooplankton in the Ross Sea and supports the vast diversity of marine megafauna
      that designates this region as an internationally protected area. Here, we
      observed the response of respiration rate to abiotic stressors associated with
      global change-environmentally relevant temperature treatments (-0.8 degrees C, 4
      degrees C) and pH treatments reflecting current-day and future modeled extremes
      (8.2, 7.95 and 7.7 pH at -0.8 degrees C; 8.11, 7.95 and 7.7 pH at 4 degrees C).
      Sampling repeatedly over a 14-day period in laboratory experiments and using
      microplate respirometry techniques, we found that the metabolic rate of juvenile
      pteropods increased in response to low-pH exposure (pH 7.7) at -0.8 degrees C, a
      near-ambient temperature. Similarly, metabolic rate increased when pteropods were
      exposed simultaneously to multiple stressors: lowered pH conditions (pH 7.7) and
      a high temperature (4 degrees C). Overall, the results showed that pCO2 and
      temperature interact additively to affect metabolic rates in pteropods.
      Furthermore, we found that L. h. antarctica can tolerate acute exposure to
      temperatures far beyond its maximal habitat temperature. Overall, L. h.
      antarctica appears to be susceptible to pH and temperature stress, two abiotic
      stressors which are expected to be especially deleterious for ectothermic marine
      metazoans in polar seas.

PMID- 29218224
TI  - Coping with differences in snow cover: the impact on the condition, physiology
      and fitness of an arctic hibernator.
AB  - The Earth's climate is changing at an unprecedented rate and, as ecologists, we
      are challenged with the difficult task of predicting how individuals and
      populations will respond to climate-induced changes to local and global
      ecosystems. Although we are beginning to understand some of the responses to
      changing seasonality, the physiological mechanisms that may drive these responses
      remain unknown. Using long-term data comparing two nearby populations (<20 km
      apart) of free-living arctic ground squirrels in northern Alaska, we have
      previously shown that the timing of spring snowmelt greatly influences their
      phenology of hibernation and reproduction in a population and site-specific
      manner. Here, we integrate these site-specific phenologies with body condition,
      stress physiology, reproductive success and juvenile recruitment to understand
      phenotypic selection in the two populations. We found that at the site with
      relatively late spring snowmelt and early autumn snow cover: (i) adult females
      were larger and in better body condition but had significantly higher stress
      hormone levels; (ii) females had similar numbers of comparably sized offspring,
      but offspring had higher stress hormone levels; and (iii) offspring density was
      lower just prior to hibernation. Thus, adult females at the two sites appear to
      use different coping strategies that allow them to maintain reproductive fitness;
      however, marked shortening of the active season because of later snowmelt in
      spring and earlier snow cover in autumn may compromise juvenile recruitment. We
      discuss the significance of these findings within the broader context of changing
      animal-environment relationships.

PMID- 29057070
TI  - Tourette syndrome research highlights from 2016.
AB  - This article presents highlights chosen from research that appeared during 2016
      on Tourette syndrome and other tic disorders. Selected articles felt to represent
      meaningful advances in the field are briefly summarized.

PMID- 29218226
TI  - Hamman's syndrome in diabetic ketoacidosis.
AB  - : Hamman's syndrome (spontaneous subcutaneous emphysema and pneumomediastinum) is
      a rare complication of diabetic ketoacidosis (DKA), with a multifactorial
      etiology. Awareness of this syndrome is important: it is likely underdiagnosed as
      the main symptom of shortness of breath is often attributed to Kussmaul's
      breathing and the findings on chest radiograph can be subtle and easily missed.
      It is also important to be aware of and consider Boerhaave's syndrome as a
      differential diagnosis, a more serious condition with a 40% mortality rate when
      diagnosis is delayed. We present a case of pneumomediastinum, pneumopericardium,
      epidural emphysema and subcutaneous emphysema complicating DKA in an eighteen
      year-old patient. We hope that increasing awareness of Hamman's syndrome, and how
      to distinguish it from Boerhaave's syndrome, will lead to better recognition and
      management of these syndromes in patients with diabetic ketoacidosis. Learning
      points: Hamman's syndrome (spontaneous subcutaneous emphysema and
      pneumomediastinum) is a rare complication of DKA.Presentation may be with chest
      or neck pain and shortness of breath, and signs are subcutaneous emphysema and
      Hamman's sign - a precordial crunching or popping sound during
      systole.Boerhaave's syndrome should be considered as a differential diagnosis,
      especially in cases with severe vomiting.The diagnosis of pneumomediastinum is
      made on chest radiograph, but a CT thorax with water-soluble oral contrast
      looking for contrast leak may be required if there is high clinical suspicion of
      Boerrhave's syndrome.Hamman's syndrome has an excellent prognosis, self-resolving
      with the correction of the ketoacidosis in all published cases in the literature.

PMID- 29218225
TI  - The gill parasite Paramoeba perurans compromises aerobic scope, swimming capacity
      and ion balance in Atlantic salmon.
AB  - The parasitic amoeba Paramoeba perurans is an aetiological agent of amoebic gill
      disease (AGD), a serious problem in seawater salmonid aquaculture globally. Other
      finfish species are also infected and infection events may be associated with
      periods of unusual high temperatures. Currently little is known about the impact
      of AGD on wild fish, but in a time with global warming and increasing aquaculture
      production this potential threat could be on the rise. A better understanding of
      the pathophysiology of infected fish is therefore warranted. In this study,
      groups of Atlantic salmon with and without AGD were tested in a large swim tunnel
      respirometer in seawater at 13 degrees C to assess oxygen uptake, swimming
      capacity and blood parameters. Standard metabolic rates were similar between
      groups, but the maximum rate of oxygen uptake was drastically reduced in infected
      fish, which resulted in a smaller aerobic scope (AS) of 203 mg O2 kg-1 h-1
      compared to 406 mg O2 kg-1 h-1 in healthy fish. The critical swimming speed was
      2.5 body lengths s-1 in infected fish and 3.0 body lengths s-1 in healthy ones.
      Furthermore, AGD fish had lower haematocrit and [haemoglobin], but similar
      condition factor compared to healthy fish. Prior to swim trials infected fish had
      higher plasma osmolality, elevated plasma [Na+], [Cl-] and [cortisol], indicating
      reduced capacity to maintain ionic homoeostasis as well as chronic stress during
      routine conditions. These results demonstrate that AGD compromises gill function
      both in terms of gas exchange and ion regulation, and consequently the capacity
      for aerobic activity is reduced. Reduced AS due to the P. perurans infections is
      likely to interfere with appetite, growth and overall survival, even more so in
      the context of a warmer and more hypoxic future.

PMID- 29188015
TI  - A multi-disciplinary perspective on emergent and future innovations in peer
      review.
AB  - Peer review of research articles is a core part of our scholarly communication
      system. In spite of its importance, the status and purpose of peer review is
      often contested. What is its role in our modern digital research and
      communications infrastructure? Does it perform to the high standards with which
      it is generally regarded? Studies of peer review have shown that it is prone to
      bias and abuse in numerous dimensions, frequently unreliable, and can fail to
      detect even fraudulent research. With the advent of web technologies, we are now
      witnessing a phase of innovation and experimentation in our approaches to peer
      review. These developments prompted us to examine emerging models of peer review
      from a range of disciplines and venues, and to ask how they might address some of
      the issues with our current systems of peer review. We examine the functionality
      of a range of social Web platforms, and compare these with the traits underlying
      a viable peer review system: quality control, quantified performance metrics as
      engagement incentives, and certification and reputation. Ideally, any new systems
      will demonstrate that they out-perform and reduce the biases of existing models
      as much as possible. We conclude that there is considerable scope for new peer
      review initiatives to be developed, each with their own potential issues and
      advantages. We also propose a novel hybrid platform model that could, at least
      partially, resolve many of the socio-technical issues associated with peer
      review, and potentially disrupt the entire scholarly communication system.
      Success for any such development relies on reaching a critical threshold of
      research community engagement with both the process and the platform, and
      therefore cannot be achieved without a significant change of incentives in
      research environments.

PMID- 29218227
TI  - Lessons learnt from a case of missed central hypothyroidism.
AB  - : We present the case of a 57-year-old lady who had a delayed diagnosis of
      central hypothyroidism on a background of Grave's thyrotoxicosis and a partial
      thyroidectomy. During the twenty years following her partial thyroidectomy, the
      patient developed a constellation of symptoms and new diagnoses, which were
      investigated by numerous specialists from various fields, namely rheumatology,
      renal and respiratory. She developed significantly impaired renal function and
      raised creatine kinase (CK). She was also referred to a tertiary neurology
      service for investigation of myositis, which resulted in inconclusive muscle
      biopsies. Recurrently normal TSH results reassured clinicians that this did not
      relate to previous thyroid dysfunction. In 2015, she developed increased
      shortness of breath and was found to have a significant pericardial effusion. The
      clinical biochemist reviewed this lady's blood results and elected to add on a
      free T4 (fT4) and free T3 (fT3), which were found to be <0.4 pmol/L (normal range
      (NR): 12-22 pmol/L) and 0.3 pmol/L (NR: 3.1-6.8 pmol/L), respectively. She was
      referred urgently to the endocrine services and commenced on Levothyroxine
      replacement for profound central hypothyroidism. Her other pituitary hormones and
      MRI were normal. In the following year, her eGFR and CK normalised, and her
      myositis symptoms, breathlessness and pericardial effusion resolved. One year
      following initiation of Levothyroxine, her fT4 and fT3 were in the normal range
      for the first time. This case highlights the pitfalls of relying purely on TSH
      for excluding hypothyroidism and the devastating effect the delay in diagnosis
      had upon this patient. Learning points: Isolated central hypothyroidism is very
      rare, but should be considered irrespective of previous thyroid disorders.If
      clinicians have a strong suspicion that a patient may have hypothyroidism despite
      normal TSH, they should ensure they measure fT3 and fT4.Laboratories that do not
      perform fT3 and fT4 routinely should review advice sent to requesting clinicians
      to include a statement explaining that a normal TSH excludes primary but not
      secondary hypothyroidism.Thyroid function tests should be performed routinely in
      patients presenting with renal impairment or a raised CK.

PMID- 29218228
TI  - Similar adverse events from two disparate agents implicate lipid inflammatory
      mediators for a role in anxiety states.
AB  - We recently reported a case in which a 54-year-old male experienced maintenance
      insomnia, generalized anxiety and panic symptoms associated with consumption of a
      fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that
      the same patient has experienced identical but more severe symptoms in response
      to the use of the leukotriene receptor antagonist montelukast, in accordance with
      other cases reported to the Food and Drug Administration. Since omega-3 fatty
      acids like EPA are precursors for the biosynthesis of eicosanoids including
      leukotrienes, a common factor to these psychiatric adverse events may be
      perturbations in this highly complex system of lipid inflammatory mediators.

PMID- 29218229
TI  - The role of arthroereisis of the subtalar joint for flatfoot in children and
      adults.
AB  - Subtalar arthroereisis has been reported as a minimally-invasive, effective and
      low-risk procedure in the treatment of flatfoot mainly in children but also in
      adults.It has been described as a standalone or adjunctive procedure, and is
      indicated in the treatment of flexible flatfoot, tibialis posterior tendon
      dysfunction, tarsal coalition and accessory navicular syndrome.Different devices
      for subtalar arthroereisis are currently used throughout the world associated
      with soft-tissue and bone procedures, depending on the surgeon rather than on
      standardised or validated protocols.Sinus tarsi pain is the most frequent
      complication, often requiring removal of the implant.To date, poor-quality
      evidence is available in the literature (Level IV and V), with only one
      comparative non-randomised study (Level II) not providing strong recommendations.
      Long-term outcome and complication rates (especially the onset of osteoarthritis)
      are still unclear. Cite this article: EFORT Open Rev 2017;2:438-446. DOI:
      10.1302/2058-5241.2.170009.

PMID- 29218231
TI  - Indications for hydrodilatation for frozen shoulder.
AB  - Frozen shoulder causes significant functional disability and pain in a population
      group constituted by patients who are often middle-aged and working.Frozen
      shoulder remains poorly understood. The available literature is limited and often
      prone to bias.A rapid, non-surgical and cost-effective treatment that reduces
      pain and restores function is an attractive option.Hydrodilatation is a potential
      first-line treatment of frozen shoulder in secondary care. Cite this article:
      EFORT Open Rev 2017;2:462-468. DOI: 10.1302/2058-5241.2.160061.

PMID- 29218232
TI  - The role of neurectomy in the management of spasticity of the upper limb.
AB  - Neurectomy is one of the treatments available to the surgeon treating patients
      with spasticity of the upper limb.Its popularity has increased in recent
      years.Accurate knowledge of the anatomical variations of the terminal branches to
      the muscles is required in order to achieve a successful outcome.Although the
      anatomy has been thoroughly studied, there are still controversies regarding the
      percentage of the nerve to be resected for a successful result, and also
      regarding the terminology that has been used in the literature to describe the
      procedure.The literature for neurectomies for the upper limb is reviewed and an
      agreement regarding terminology is proposed. Cite this article: EFORT Open Rev
      2017;2:469-473. DOI: 10.1302/2058-5241.2.160074.

PMID- 29218230
TI  - Spondylodiscitis revisited.
AB  - Spondylodiscitis may involve the vertebral bodies, intervertebral discs,
      paravertebral structures and spinal canal, with potentially high morbidity and
      mortality rates.A rise in the susceptible population and improved diagnosis have
      increased the reported incidence of the disease in recent years.Blood cultures,
      appropriate imaging and biopsy are essential for diagnosis and treatment.Most
      patients are successfully treated by conservative means; however, some patients
      may require surgical treatment.Surgical indications include doubtful diagnosis,
      progressive neurological deficits, progressive spinal deformity, failure to
      respond to treatment, and unresolved pain. Cite this article: EFORT Open Rev
      2017;2:447-461. DOI: 10.1302/2058-5241.2.160062.

PMID- 29218235
TI  - Experimental Validation of the Pseudo-Rigid-Body Model of the MRI-Actuated
      Catheter.
AB  - An MRI-actuated catheter is a novel robotic catheter system that utilizes the MRI
      for both remote steering and visualization for catheter ablation of atrial
      fibrillation. Planning and control of the catheter requires a sufficiently fast
      yet accurate model of the catheter. The pseudo-rigid-body (PRB) model offers a
      reasonable trade-off between speed and accuracy by approximating the continuum
      catheter as rigid links connected by flexible joints, thus reducing the infinite
      degrees of freedom of the continuum mechanism to a finite one. In this paper, a
      PRB model of the MRI-actuated catheter is validated experimentally by comparing
      the deflections of the PRB model with the deflections of the catheter prototype.

PMID- 29218233
TI  - Targeted Delivery of siRNA Therapeutics to Malignant Tumors.
AB  - Over the past 20 years, a diverse group of ligands targeting surface biomarkers
      or receptors has been identified with several investigated to target siRNA to
      tumors. Many approaches to developing tumor-homing peptides, RNA and DNA
      aptamers, and single-chain variable fragment antibodies by using phage display,
      in vitro evolution, and recombinant antibody methods could not have been imagined
      by researchers in the 1980s. Despite these many scientific advances, there is no
      reason to expect that the ligand field will not continue to evolve. From
      development of ligands based on novel or existing biomarkers to linking ligands
      to drugs and gene and antisense delivery systems, several fields have coalesced
      to facilitate ligand-directed siRNA therapeutics. In this review, we discuss the
      major categories of ligand-targeted siRNA therapeutics for tumors, as well as the
      different strategies to identify new ligands.

PMID- 29218236
TI  - PSMB5 plays a dual role in cancer development and immunosuppression.
AB  - Tumor progression and metastasis are dependent on the intrinsic properties of
      tumor cells and the influence of microenvironment including the immune system. It
      would be important to identify target drug that can inhibit cancer cell and
      activate immune cells. Proteasome beta subunits (PSMB) family, one component of
      the ubiquitin-proteasome system, has been demonstrated to play an important role
      in tumor cells and immune cells. Therefore, we used a bioinformatics approach to
      examine the potential role of PSMB family. Analysis of breast TCGA and METABRIC
      database revealed that high expression of PSMB5 was observed in breast cancer
      tissue and that high expression of PSMB5 predicted worse survival. In addition,
      high expression of PSMB5 was observed in M2 macrophages. Based on our
      bioinformatics analysis, we hypothesized that PSMB5 contained immunosuppressive
      and oncogenic characteristics. To study the effects of PSMB5 on the cancer cell
      and macrophage in vitro, we silenced PSMB5 expression with shRNA in THP-1
      monocytes and MDA-MB-231 cells respectively. Knockdown of PSMB5 promoted human
      THP-1 monocyte differentiation into M1 macrophage. On the other hand, knockdown
      PSMB5 gene expression inhibited MDA-MB-231 cell growth and migration by colony
      formation assay and boyden chamber. Collectively, our data demonstrated that
      delivery of PSMB5 shRNA suppressed cell growth and activated defensive M1
      macrophages in vitro. Furthermore, lentiviral delivery of PSMB5 shRNA
      significantly decreased tumor growth in a subcutaneous mouse model. In
      conclusion, our bioinformatics study and functional experiments revealed that
      PSMB5 served as novel cancer therapeutic targets. These results also demonstrated
      a novel translational approach to improve cancer immunotherapy.

PMID- 29218234
TI  - The emerging role of zinc transporters in cellular homeostasis and cancer.
AB  - Zinc is an essential micronutrient that plays a role in the structural or
      enzymatic functions of many cellular proteins. Cellular zinc homeostasis involves
      the opposing action of two families of metal transporters: the ZnT (SLC30) family
      that functions to reduce cytoplasmic zinc concentrations and the ZIP (SLC39)
      family that functions to increase cytoplasmic zinc concentrations. Fluctuations
      in intracellular zinc levels mediated by these transporter families affect
      signaling pathways involved in normal cell development, growth, differentiation
      and death. Consequently, changes in zinc transporter localization and function
      resulting in zinc dyshomeostasis have pathophysiological effects. Zinc
      dyshomeostasis has been implicated in the progression of cancer. Here we review
      recent progress toward understanding the structural basis for zinc transport by
      ZnT and ZIP family proteins, as well as highlight the roles of zinc as a
      signaling molecule in physiological conditions and in various cancers. As zinc is
      emerging as an important signaling molecule in the development and progression of
      cancer, the ZnT and ZIP transporters that regulate cellular zinc homeostasis are
      promising candidates for targeted cancer therapy.

PMID- 29218237
TI  - Increased miR-21a provides metabolic advantages through suppression of FBP1
      expression in non-small cell lung cancer cells.
AB  - Lung cancer is the most common solid tumor and the leading cause of cancer
      related mortality worldwide. miR-21 is one of the most commonly observed aberrant
      miRNAs in human cancers. However, the biological roles of miR-21 in glucose
      metabolism of non-small cell lung cancer (NSCLC) cells remain unknown. In the
      present study, our findings demonstrated that miR-21 promoted glucose uptake and
      increased TXNIP expression. miR-21 increased lactate generation and decreased
      oxygen consumption in NSCLC cells. Moreover, we found that miR-21 promoted
      glycolysis and decreased OXPHOS. Mechanistically, fructose-1,6-biphosphatase
      (FBP1) was a direct target of miR-21 and observed a negative correlation between
      miR-21 and FBP1 in NSCLC samples. Restoring FBP1 expression reversed the effects
      induced by miR-21 overexpression in NSCLC cells. Together, our findings suggest
      the critical role of miR-21 in glucose metabolism through suppression of FBP1 in
      NSCLC cells. miR-21 may be a potential target of NSCLC treatment.

PMID- 29218238
TI  - MicroRNA-936 induces cell cycle arrest and inhibits glioma cell proliferation by
      targeting CKS1.
AB  - Accumulating evidence shows that microRNAs play important roles in cancers,
      including glioma. MiRNAs have been shown to participate in a variety of cellular
      functions including cell apoptosis, cell proliferation, neural development, and
      stem cell differentiation. Previous studies reported that miR-936 levels were
      downregulated in glioma specimens. Here, we further investigate the potential
      role of miR-936 in glioma. Quantitative reverse transcription-PCR was applied to
      detect the expression of mir-936 in glioma specimens. The direct targets of miR
      936 were identified by bioinformatics analysis and were further validated by
      immunoblotting and luciferase reporter assay. The effects of miR-936 on glioma
      cell proliferation and cell cycle of glioma cells were analyzed by Cell-Counting
      Kit 8 assay, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry
      assays. A xenograft model was used to study the effect of miR-936 on tumor growth
      and angiogenesis. Expression levels of miR-936 were greatly downregulated in
      glioma specimens, CKS1 was confirmed as a direct target of miR-936. The glioma
      cell cycle was blocked to G1 by negatively regulating CKS1 and its downstream
      signaling pathway, Akt-ERK1/2. Furthermore, overexpression of CKS1 rescued the
      inhibitory effects of miR-936. In vivo studies revealed that increased levels of
      miR-936 delayed the growth of tumors. Taken together, mir-936 may act as a glioma
      suppressor by targeting CKS1.

PMID- 29218239
TI  - CSF-1R regulates non-small cell lung cancer cells dissemination through Wnt3a
      signaling.
AB  - Therapeutic antibodies targeting colony stimulating factor 1 receptor (CSF-1R) to
      block colony stimulating factor-1/colony stimulating factor 1 receptor (CSF-1/CSF
      R) signaling axis have exhibit remarkable efficacy in the treatment of malignant
      tumor. Yet, little is known about the effects of intrinsic CSF-1R in human non
      small-cell carcinoma (NSCLC). Here we demonstrated that NSCLC cell-intrinsic CSF
      1R promoted cells growth and metastasis both in vitro and in vivo. CSF-1R knocked
      down by transfecting with shRNA target CSF-1R suppressed NSCLC cells
      proliferation and tumor growth in nude mice. Conversely, ectopic expression of
      CSF-1R promoted cells proliferation and accelerated tumor growth.
      Mechanistically, the NSCLC CSF-1R modulated downstream effectors of
      phosphatidylinositol 3-kinase (PI3K) signaling. In addition, CSF-1R
      overexpression significantly enhanced NSCLC cells mobility, invasion and
      epithelial-mesenchymal transition (EMT) process, whereas silencing CSF-1R
      inhibits these phenotypes. Microarray analysis suggested that Wnt family member
      3a (Wnt3a) function as a downstream factor of CSF-1R. On account of this, we
      future identified CSF-1R/Wnt3a a signaling pathway sustained NSCLC cells
      metastasis. Finally, in patients, CSF-1R and Wnt3a expression positively
      correlated with the of NSCLC patients. Our results identify NSCLC cell intrinsic
      functions of CSF-1R/Wnt3a axis in dissemination of NSCLC.

PMID- 29218240
TI  - The long noncoding RNA LINC00473, a target of microRNA 34a, promotes
      tumorigenesis by inhibiting ILF2 degradation in cervical cancer.
AB  - Cervical cancer is one of the most common gynecological malignancies in women
      worldwide. The long non-coding RNA (lncRNA) LINC00473 is increased in some human
      cancer tissues and it plays important roles in tumorigenesis. However, neither
      the expression pattern nor the biological functions of LINC00473 have been
      elucidated in cervical cancer so far. In the present study, gain- and loss-of
      function assays showed that LINC00473 promoted cell proliferation and inhibited
      cell apoptosis in cervical cancer cells in vitro. Moreover, we found that
      LINC00473 enhanced the growth of cervical cancer cells in vivo. Mechanistic
      investigation showed that LINC00473 directly interacted with ILF2 and suppressed
      its degradation. Finally, we demonstrated that miR-34a reduced the stability of
      LINC00473. These findings may have important implications for developing novel
      therapeutic strategies for cervical cancer.

PMID- 29218241
TI  - Reticulocalbin 2 correlates with recurrence and prognosis in colorectal cancer.
AB  - Reticulocalbin (RCN) family members could play oncogenic roles in human
      malignancies and facilitate tumor cell proliferation and metastasis. However, the
      expression pattern and potential function of Reticulocalbin 2 (RCN2) in
      colorectal cancer has not been addressed yet. In the present study, we
      investigated the protein expression of RCN2 by immunohistochemistry assay, and
      analyzed its association with tumor progression, recurrence and prognosis in 326
      cases of patients. Results suggested that the expression of RCN2 was up-regulated
      in colorectal cancer compared with paired adjacent nontumor specimens. RCN2
      expression was closely related to tumor size and the depth of invasion. Kaplan
      Meier analysis proved that RCN2 was associated with both disease-free survival
      and overall survival of patients with colorectal cancer. Moreover, cox's
      proportional hazards analysis showed that high RCN2 expression was an independent
      prognostic marker of poor outcome. Consistently, overexpressing RCN2 promoted CRC
      cell proliferation both in vitro and in vivo and knockdown RCN2 showed the
      opposite results. These results provided the first evidence that RCN2 level was
      increased in colorectal cancer and significantly correlated with tumor growth and
      proliferation. It also indicated that RCN2 might serve as a potential marker of
      tumor recurrence and prognosis of colorectal cancer.

PMID- 29218242
TI  - Long noncoding RNA lncBRM facilitates the proliferation, migration and invasion
      of ovarian cancer cells via upregulation of Sox4.
AB  - Ovarian cancer (OC) is one of the most fatal gynecological cancer in women
      worldwide. Long noncoding RNA (lncRNA) lncBRM was found to be associated with the
      progression and prognosis of hepatocellular carcinoma (HCC). However, the
      expression level, clinical significance and functions in OC tumorigenesis and
      progression remain unclear. Our present research demonstrated that lncBRM
      expression was significantly increased in OC tissues. Upregulation of lncBRM
      expression was correlated with histological grade, FIGO stages, lymph node
      metastasis and poor prognosis of patients with OC. Functional assays showed that
      lncBRM positively regulated cell proliferation, migration and invasion in OC.
      Moreover, lncBRM upregulated Sox4 by competitively binding miR-204. Together,
      lncBRM functions as an oncogene in OC and can be a promising therapeutic target
      for OC treatment.

PMID- 29218243
TI  - Elevated HBXIP expression is associated with aggressive phenotype and poor
      prognosis in esophageal squamous cell carcinoma.
AB  - The oncoprotein hepatitis B virus X-interacting protein (HBXIP) has been
      suggested to play an essential role in several malignancies. However, the
      clinicopathological significance and prognostic value of HBXIP expression in
      esophageal squamous cell carcinoma (ESCC) is still unknown. Therefore the aim of
      this study was to characterize HBXIP expression and its prognostic value in ESCC.
      Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were
      performed to assess the mRNA and protein expression of HBXIP in ESCC tissues and
      cell lines. Immunohistochemistry (IHC) was conducted to characterize the
      expression pattern of HBXIP in 152 archived paraffin-embedded ESCC and matched
      nontumorous tissues. The mRNA and protein expression of HBXIP in ESCC tissues was
      significantly higher than those in adjacent nontumorous tissues. High HBXIP
      expression was associated with histological grade (P=0.016), depth of tumor
      invasion (P=0.012), lymph node metastasis (P<0.001) and TNM stage (P=0.002).
      Kaplan-Meier analysis indicated that ESCC patients with high HBXIP expression had
      poor disease-free survival (DFS) and overall survival (OS). Furthermore,
      multivariate Cox regression analyses demonstrated that HBXIP expression remained
      an independent prognostic factor for DFS and OS. Collectively, our present study
      demonstrated that HBXIP may be a candidate molecular prognostic marker for ESCC.

PMID- 29218244
TI  - Exosomal TGF-beta1 is correlated with lymphatic metastasis of gastric cancers.
AB  - Exosomes are nano-vesicles transporting bioactive material between cells. This
      study explored the prognostic association of exosomal TGF-beta1 with lymph node
      (LN) metastasis of gastric cancer (GC). TGF-beta1 expressions in the exosomes
      isolated from the gastroepiploic veins of 61 GC patients analyzed by ELISA. The
      regulatory T (Treg) cells in celiac LNs of gastric cancer analyzed by
      immunohistochemistry. Exosomal TGF-beta1 expression and the ratio of Treg cells
      in draining LNs were both significantly associated with pathological stages and
      LN metastasis of gastric cancer. Besides, the exosomal TGF-beta1 expression and
      Treg proportion in LN were also significantly correlated in gastric cancer
      patients. Recombinant TGF-beta1 and exosomes isolated from GC patients were used
      to induce FOXP3+ Treg cells from naive T cells in vitro. Compared to the control,
      recombinant TGF-beta1 induced more CD25 (41%), FOXP3 (19%) and CTLA-4 (47%),
      while reduced CD45RA expression by 38% in primary naive T cell cultures (p<0.01).
      Exosomes treatment induced more CD25 and 45% higher CTLA-4 expression, and
      increased 29% higher of CD45RA-negative cells than recombinant TGF-beta1 did
      (p<0.01). Adding TGF-beta1 neutralizing antibody partially abrogated the effects
      of exosomes on Treg induction. Our study showed exosomal TGF-beta1 related to
      lymph node metastasis and the ratio of Treg cells in lymph nodes of gastric
      cancers. Exosomes from gastric cancer patients could induce Treg cells formation
      through the effect of TGF-beta1.

PMID- 29218245
TI  - Expression of miR-149-3p inhibits proliferation, migration, and invasion of
      bladder cancer by targeting S100A4.
AB  - MicroRNAs play key roles during various crucial cell processes, such as
      proliferation, migration, and invasion. In addition, microRNAs have been shown to
      possess oncogenic and tumor suppressive functions in human cancers. Increasing
      evidence has clarified that miR-149-3p, a novel cancer-related microRNA, plays an
      important role in suppression of proliferation, migration, and invasion; however,
      the effect and mechanisms underlying the miR-149-3p effect in bladder cancer
      (BCa) remain unclear. In the current study we found that the increased expression
      of miR-149-3p significantly suppressed cell proliferation, migration, and
      invasion ability in BCa. The suppressive effect was related to S100A4. A further
      investigation showed that miR-149-3p negatively regulated S100A4, as verified by
      the luciferase reporter assay. Furthermore, our study showed that S100A4 mediated
      the anti-metastatic effects of miR-149-3p on proliferation, migration, and
      invasion of BCa cells. Analysis of a xenograft mouse model showed that miR-149-3p
      expression significantly decreased tumor growth by targeting S100A4. Taken
      together, these data indicate that S100A4 promotes cell growth, migration, and
      invasion and can by reversed by miR-149-3p in BCa.

PMID- 29218246
TI  - Angiopoietin-like protein 2 facilitates non-small cell lung cancer progression by
      promoting the polarization of M2 tumor-associated macrophages.
AB  - The functional phenotypes (M1 and M2) of tumor-associated macrophages (TAMs) are
      influenced by the tumor microenvironment (TME) and contribute greatly to the
      development of non-small cell lung cancer (NSCLC). However, the molecular
      mechanisms for TAM polarization remain unclear. Angiopoietin-like protein 2
      (Angptl2) is involved in tumor progression. In this study, Angptl2 expression was
      aberrantly increased in NSCLC cells and positively correlated with TAM
      infiltration, tumor size and poor patient survival. Moreover, in vitro tumor cell
      macrophage co-culture and recombinant protein stimulation revealed that Angptl2
      fostered the M2 polarization of TAMs through the p65 nuclear factor-kappa B (NF
      KB) pathway. In addition, Angptl2-promoted TAM enhanced proliferation, invasion,
      and migration of NSCLC cells and the tube formation of human umbilical vein
      endothelial cells (HUVECs). In vivo, TAM depletion inhibited the tumor growth
      induced by Angptl2. Here, for the first time, we determined that Angptl2 promoted
      the M2 polarization of TAMs and enhanced NSCLC progression. Interfering with
      Angptl2 might be an effective strategy for reprogramming TAM polarization in
      NSCLC, providing a promising therapy for NSCLC treatment.

PMID- 29218247
TI  - AKIP1 promoted epithelial-mesenchymal transition of non-small-cell lung cancer
      via transactivating ZEB1.
AB  - Non-small-cell lung cancer (NSCLC) is one of the leading death-related
      malignancies worldwide with elusive molecular mechanisms. A-kinase interacting
      protein 1 (AKIP1) is an important regulator controlling metastasis,
      lymphangiogenesis and angiogenesis. However, the role of AKIP1 in NSCLC
      progression is still little known. Here, we found that AKIP1 was overexpressed in
      NSCLC specimens as well as cell lines. Overexpression of AKIP1 in NSLCC tissues
      was positively correlated with TNM stage, lymph node metastasis and poor
      prognosis. Knockdown of AKIP1 inhibited NSCLC cell migration, invasion and
      epithelial-mesenchymal transition (EMT), as indicated by the up-regulation of
      mesenchymal markers (fibronectin and vimentin) and down-regulation of epithelial
      marker E-cadherin, whereas overexpression of AKIP1 showed the opposite effects.
      Moreover, AKIP1 transactivated Zinc Finger E-Box Binding Homeobox 1 (ZEB1)
      expression via directly binding to ZEB1 promoter, thereby leading to E-cadherin
      transcriptional repression. Additionally, we observed that the binding efficiency
      of AKIP1 within ZEB1 promotor was determined by the interaction between AKIP1 and
      SP1. In conclusion, AKIP1 promoted EMT of NSCLC via transactivating ZEB1,
      suggesting AKIP1 as a potential therapeutic target.

PMID- 29218248
TI  - Propafenone suppresses esophageal cancer proliferation through inducing
      mitochondrial dysfunction.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant
      tumors with poor survival and limited therapeutic options. The aim of this study
      is to identify novel anticancer strategies from existing Food and Drug
      Administration (FDA)-approved drugs that have been used to clinically treat other
      diseases. Here, propafenone, an antiarrhythmic medication, was found to induce
      apoptosis and exert a significantly inhibitory effect on the proliferation and
      colony-forming ability of ESCC cells in a dose-dependent manner without observed
      cytotoxicity on normal esophageal epithelial cells. Furthermore, propafenone
      markedly suppressed growth of tumor xenografts in nude mice by reducing the Ki-67
      proliferation index and angiogenesis but did not damage the vital organs of the
      animals. Mechanistically, our data from the proteomics, Western blot and flow
      cytometry analyses demonstrated that propafenone caused mitochondrial dysfunction
      as indicated by a decreased mitochondrial membrane potential and reduced
      expression of Bcl-xL and Bcl-2. In summary, this study provides the first
      evidence that propafenone, an FDA-approved drug to treat arrhythmias, could be a
      novel therapeutic strategy for treating ESCC without obvious side effects.

PMID- 29218249
TI  - Pericellular regulation of prostate cancer expressed kallikrein-related
      peptidases and matrix metalloproteinases by cell surface serine proteases.
AB  - We provide evidence of a pericellular network of proteases that are elevated and
      co-expressed in prostate cancer. The network involves the membrane bound serine
      proteases hepsin and TMPRSS2, the secreted kallikrein-related peptidases KLK4 and
      KLK14, and the secreted matrix metalloproteinases MMP-3 and MMP-9. Western blot
      analysis of cell lysates, conditioned cell culture media, immunoprecipitates and
      cell surface proteins, demonstrates a network of interactions centred largely at
      the plasma membrane, with the Arg/Lys specific proteases hepsin and TMPRSS2 key
      regulators of the network. Our data demonstrate that like TMPRSS2, hepsin is able
      to autoactivate. Active hepsin degrades KLK4, generating a cell associated
      degradation product with corresponding reduction in levels of cell-free KLK4. In
      contrast hepsin activates KLK14. TMPRSS2 appears to cleave amino terminal to the
      KLK4 activation site such that it is available for further processing to generate
      the active KLK4 protease. In contrast with hepsin, TMPRSS2 degrades KLK14. In
      addition to these direct mechanisms of regulation, hepsin and TMPRSS2 indirectly
      modulate KLK4 activity by cleaving the KLK4-activating protease MMP-3. Hepsin and
      TMPRSS2 also activate MMP-9, which similar to MMP-3, associates with the cell
      surface. Interestingly our data also show that proteolysis occurs between the
      membrane spanning and catalytic domains of hepsin and TMPRSS2. Hepsin cleavage
      occurs via an autoproteolytic mechanism, whereas TMPRSS2 cleavage is mediated by
      KLK14. Hepsin and TMPRSS2 are not shed from the cell surface but proteolysis
      likely disrupts domains that regulate the proteolytic activity of these
      proteases. Immunocytochemical analyses demonstrate that hepsin and TMPRSS2
      colocalize on the cell surface with the secreted serine proteases KLK4 and KLK14,
      only in membrane protrusions, suggesting that reciprocal proteolytic interactions
      occur in defined cellular structures that are important during cancer
      dissemination for cell migration, invasion and survival. Also of note,
      immunohistochemical analysis of serial sections of prostate tumor demonstrated
      significant overlapping expression of the six proteases in vivo. Collectively
      these data suggest the possibility that the novel proteolytic network identified
      by us, will be most important during active dissemination of prostate cancers,
      and that its disruption could inhibit metastasis.

PMID- 29218251
TI  - Overexpression of CST4 promotes gastric cancer aggressiveness by activating the
      ELFN2 signaling pathway.
AB  - Gastric cancer is one of the most lethal malignancies of gastrointestinal cancer
      and its prognosis remains dismal because of the paucity of effective therapeutic
      targets. Here, we show that cystatin 4 (CST4) is markedly upregulated in gastric
      cancer cell lines and clinical tissues. Ectopic expression of CST4 in gastric
      cancer cells promoted proliferation, migration, and invasion of gastric cancer
      cells in vitro. Furthermore, CST4 overexpression significantly promoted the
      tumorigenicity of gastric cancer cells in vivo, whereas silencing endogenous CST4
      caused an opposite outcome. In addition, extracellular leucine rich repeat and
      fibronectin type III domain containing 2 (ELFN2) was identified as a downstream
      target of CST4 in gastric cancer cells and was positively correlated with ELFN2
      expression in gastric cancer tissues. Finally, we demonstrated that CST4 enhanced
      gastric cancer aggressiveness by regulating ELFN2 signaling. Together, our
      results provide new evidence that CST4 overexpression promotes the progression of
      gastric cancer and might represent a novel therapeutic target for its treatment.

PMID- 29218250
TI  - Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF
      complex in clear cell renal cell carcinoma development.
AB  - Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of
      hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene.
      Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene
      coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found
      suggesting potential impairment of this complex function in ccRCC. In this study
      we assessed the extent to which the core SWI/SNF complex subunit - INI1
      (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the
      development of this type of cancer. The evaluation of INI1 protein level in
      samples from 50 patients with diagnosed ccRCC, including three displaying
      rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the
      conventional ccRCC cells exhibited reduced INI1 level. This indicated the
      rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The
      reduced INI1 protein level observed in all conventional ccRCC cases used in this
      study correlated with decreased SMARCB1 gene expression at the transcript level.
      Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted
      in the elevation of endogenous SMARCB1 transcript level indicating that the INI1
      dependent regulatory feedback loop controlling expression of this gene is
      affected in ccRCC Moreover, the set of INI1 target genes including i.e.
      CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In
      summary, we demonstrated that the inactivation of INI1 may be of high importance
      for ccRCC development and aggressiveness.

PMID- 29218252
TI  - miR-145 targets the SOX11 3'UTR to suppress endometrial cancer growth.
AB  - To explore the functions of SOX (Sex determining Region Y-related HMG-box) family
      genes in endometrial cancer (EC) and determine the influence of miR-145/SOX11 on
      EC cell functions. The relationship between miR-145 and SOX11 was confirmed using
      TargetScan, miRNA databases and dual-luciferase reporter gene assays. The
      expression of SOX11 mRNA in tissue specimens was examined using RT-qPCR, while
      SOX11 protein expression in tissues and cell lines were detected through
      immunohistochemistry (IHC) and western blotting. After transfection using
      Lipofectamine 2000, the proliferation, migration, invasion and apoptosis of ECC-1
      and HEC-1-A cells were assessed through colony formation, transwell and flow
      cytometry assays. The correlation of SOX11 expression with the prognosis outcomes
      of patients was analyzed using Kaplan-Meier analysis and the log-rank test. SOX11
      showed high expression in EC, which is negatively correlated with a poor
      prognostic outcome of EC patients. The expression of miR-145 was lower in EC
      tissues than in adjacent tissues. MiR-145 significantly reduced the expression of
      SOX11. In ECC-1 cells, miR-145 suppressed the propagation, migration, and
      invasion of cells and promoted cell apoptosis. MiR-145 also inhibited the
      proliferation, migration, and invasion of HEC-1-A cells and facilitated cell
      apoptosis by inhibiting SOX11. MiR-145 targeted site 3 (3615) of the SOX11 3'UTR
      to affect the expression of SOX11. MiR-145 and its target gene SOX11 could serve
      as diagnostic markers for EC. MiR-145 targets the SOX11 3'UTR to inhibit its
      expression and suppress the propagation and metastasis of EC cells.

PMID- 29218253
TI  - Clinical applications of urinary cell-free DNA in cancer: current insights and
      promising future.
AB  - Liquid biopsy is gaining significant attention as a tool for unveiling the
      molecular landscape of tumor and holds great promise for individualized medicine
      for cancer. Cell-free DNA serves as an extremely important component of liquid
      biopsy for cancer, and cell-free DNA in urine is even promising due to the
      remarkable advantage of urine as an ultra-noninvasive sample source over tissue
      and blood. Compared with the widely studied cell-free DNA in blood, less is known
      about the role of urinary cell-free DNA. Urinary cell-free DNA has the ability to
      give comprehensive and crucial information on cancer as it carries genetic
      messages from cells shedding directly into urine as well as transporting from
      circulation. As an indispensable component of liquid biopsy, urinary cell-free
      DNA is believed to have the potential of being a useful and ultra-noninvasive
      tool for cancer screening, diagnosis, prognosis, and monitoring of cancer
      progression and therapeutic effect. In this review, we provide the current
      insights into the clinical applications of urinary cell-free DNA in cancer. We
      also introduce the basic biological significance and some technical issues in the
      detection of urinary cell-free DNA.

PMID- 29218254
TI  - Bone microenvironment has an influence on the histological response of
      osteosarcoma to chemotherapy: retrospective analysis and preclinical modeling.
AB  - Osteosarcoma, the most common malignant primary bone tumor, is currently treated
      with chemotherapy and surgery. The effectiveness of chemotherapy is evaluated by
      means of histological analysis of tumor necrosis, known as "the Huvos score".
      However, 25% of the patients initially considered good responders will relapse.
      In our practice, strong tissue heterogeneity around the residual viable cells of
      the osteosarcoma is observed, but this is not taken into account by the Huvos
      score, as it is only an average. The objective is to determine whether
      heterogeneity in the osteosarcoma's microenvironment can play a role in the
      histological response to chemotherapy. Two complementary approaches have been
      developed: (i) the therapeutic response to several monotherapies (ifosfamide,
      cisplatin, doxorubicin) has been compared to tumor growth and the necrosis levels
      in different preclinical syngeneic osteosarcoma models, mimicking various
      microenvironments by injecting the tumor cells into subcutaneous, intra-muscular
      paratibial, or intra-osseous sites; (ii) a retrospective analysis was performed
      on patients' osteoblastic osteosarcoma biopsies. Tissue localization mapping of
      residual live tumor cell colonies was evaluated for potential correlation with
      overall survival. The results of the preclinical studies showed a difference in
      tumor growth depending on the osteosarcoma model, with a higher rate in bone
      sites compared to subcutaneous tumors. For the therapeutic response, a higher
      response to doxorubicin was observed in the intra-osseous model compared to the
      intra-muscular model for tumor growth (P = 0.013) and necrosis (P = 0.007). These
      data strongly suggest that the microenvironment plays a role in how osteosarcoma
      responds to chemotherapy. The retrospective analysis showed no significant
      survival difference between residual cell sites, although the soft tissues may be
      seen as a potential negative factor.

PMID- 29218255
TI  - Oncology Section EDGE Task Force on Urogenital Cancer: A Systematic Review of
      Clinical Measures for Incontinence.
AB  - Background: Compared to the general population, women and men with urogenital and
      colorectal cancer experience higher rates of urinary and fecal incontinence.
      Although a variety of measures exist to assess these areas, currently, there are
      no guidelines recommending which outcomes rehabilitation professionals should
      administer to examine these impairments in those with cancer. Purpose: To
      identify outcome measures for assessing urinary and fecal incontinence and
      evaluate their psychometric data and applicability to the cancer population.
      Methods: Multiple electronic databases (CINAHL, Medline, PsycInfo) were reviewed
      using specific search terms to locate articles that identify outcome measures
      assessing urinary and fecal incontinence. As part of a larger effort to identify
      outcome measures for both incontinence and sexual dysfunction, 1118 articles were
      initially identified, 228 articles were reviewed, and 37 outcome measures were
      selected for analysis, 13 of which were related to urinary and fecal
      incontinence. Each incontinence outcome measure was independently reviewed and
      rated by two reviewers using the Cancer EDGE Task Force Outcome Measure Rating
      Form. Any discrepancies between reviewers were discussed and an overall
      recommendation for each outcome measure was made using the 4-point Cancer EDGE
      Task Force Rating Scale. Results: The Task Force was able to highly recommend 1
      measure addressing urinary incontinence (American Urological Association Symptom
      Index) and 2 measures assessing both urinary and fecal incontinence (Pelvic Floor
      Distress Inventory - Short Form, Pelvic Floor Impact Questionnaire - Short Form).
      The Task Force also recommended two measures of urinary incontinence that
      demonstrated strong psychometric properties, but had not yet been evaluated in
      the cancer population (Incontinence Quality of Life Questionnaire, International
      Consultation on Incontinence Questionnaire - Short Form). The Task Force was
      unable to recommend any measures that solely addressed fecal incontinence.
      Conclusions: Five of the 13 outcome measures assessing urinary incontinence and
      two of the 13 measures assessing both urinary and fecal incontinence demonstrated
      satisfactory psychometric properties and application to the urogenital cancer
      population and are thereby recommended for use by the Task Force.

PMID- 29218256
TI  - Intracranial Anatomical Triangles: A Comprehensive Illustrated Review.
AB  - There are multiple anatomical triangles of the skull base. However, to our
      knowledge, there has been no comprehensive review of these geometric landmarks.
      To allow for a safe and consistent approach to lesions of the skull base such as
      those near the internal carotid artery, internal acoustic meatus, and cavernous
      sinus, a comprehensive review of the variations with illustrations is required.
      This article provides an overview of the anatomical borders, dimensions, and
      surgical implications as well as illustrations of the major skull base triangles.

PMID- 29218257
TI  - Pulmonary Tuberculosis Versus Recurrent Chemotherapy-Induced Pneumonitis: A
      Clinical Dilemma.
AB  - Chemotherapy-induced lung toxicity can affect pulmonary parenchyma, pleura,
      airways, pulmonary vascular system, mediastinum or the neuromuscular system that
      is responsible for respiration. Chemotherapy-induced pulmonary toxicity is a
      diagnosis of exclusion. When the patients with malignancies develop pulmonary
      toxicity such as pneumonitis and distinguishing it from alternative diseases such
      as infectious, thrombotic, cardiac, malignant or exacerbation of chronic lung
      conditions can be difficult. Moreover, such patients are often immunosuppressed,
      physically stressed from the underlying disease and the cancer treatment and
      hence, more susceptible to usual and unusual or opportunistic infections. We
      describe a patient with pancreatic cancer who was assumed to develop recurrent
      chemotherapy-induced pneumonitis to various agents, including irinotecan and
      docetaxel, but subsequently proved to have reactivation of tuberculosis (TB).
      With tuberculosis not being uncommon in cancer patients, we now believe that his
      symptoms could all have been because of an active tuberculosis infection,
      especially with his latent TB history and pulmonary symptoms. Information about
      the link between the treatment of solid-organ cancers and TB is very limited. Our
      case underlines the recognition about this link of chemotherapy and TB as well as
      remind us of the lack of widely accepted and established standards for both
      screenings for latent TB and for the treatment of active TB in the patients
      undergoing systemic treatment. A simple test such as a tuberculin skin test or
      QuantiFERON-TB Gold test can be used to rule out latent TB before beginning
      radiotherapy or chemotherapy in these patients. Clinicians must be cognizant of
      this condition to prevent further morbidity and mortality in these cancer
      patients and include activated TB in the differential diagnosis of pulmonary
      toxicity suspected in a patient undergoing chemotherapy with unexplained
      pulmonary findings.

PMID- 29218258
TI  - Breaking the Magic: Mouth and Genital Ulcers with Inflamed Cartilage Syndrome.
AB  - Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome refers to a
      condition in which features of Behcet's disease (BD) and relapsing polychondritis
      (RP) occur in the same individual. The existence of MAGIC syndrome suggests a
      potential common etiology for BD and RP. However, connecting these two diseases
      and referring to this condition as MAGIC syndrome might have been premature, as
      there is currently insufficient knowledge on BD and RP. In this critical review,
      we argue that these two clinical entities could possibly be unique disease
      processes rather than two ends of the same disease spectrum. Distinguishing the
      clinical difference between BD and RP is critical for the management of patients
      diagnosed with MAGIC syndrome, as biological therapeutic approaches for BD and RP
      differ. Also, inaccurate perception regarding the relationship of these two
      diseases could mislead researchers in their endeavors to unravel the
      pathophysiological mechanisms behind these two diseases.

PMID- 29218259
TI  - Melena as Initial Presentation of Adenocarcinoma in Pancreatic Tail.
AB  - Melena associated with gastric varices, in the setting of possible obstructing
      pancreatic adenocarcinoma, has been poorly documented as an initial presenting
      sign for pancreatic malignancy. Considering the late presentation of patients
      with pancreatic malignancy, it is important to consider all potential presenting
      symptoms for the early detection and treatment of pancreatic malignancy. Below,
      we present a patient with no history of liver pathology, who presents with melena
      and gastric varices, likely relating to portal hypertension in the setting of an
      obstructing pancreatic malignancy.

PMID- 29218260
TI  - A Case of Streptococcus anginosus Brain Abscess Caused by Contiguous Spread from
      Sinusitis in an Immunocompetent Patient.
AB  - Brain abscesses are infections of the brain parenchyma that can arise from either
      contiguous spread from local infection or by hematogenous spread from a distant
      site. Streptococcus anginosus of the Streptococcus anginosus group (SAG) is a
      commensal microbe of the mucosae of the oral cavity, gastrointestinal tract, and
      urogenital tract. We present a case of mono-microbial brain abscess caused by
      contiguous spread from relatively asymptomatic sinusitis that initially presented
      as a subdural hemorrhage on computed tomography. A 70-year-old male presented,
      obtunded, with a Glasgow Coma Score of eight. The patient seized on arrival. A
      computed tomography scan was read as a subdural hemorrhage, and magnetic
      resonance imaging showed a heterogeneous area at the anterior tip of the left
      frontal lobe interpreted as a frontoparietal abscess, along with pansinusitis.
      Craniotomy revealed a loculated abscess. Culture grew only Streptococcus
      anginosus. The patient did well postoperatively, was extubated by day five with
      rapidly improving neurological function, and was discharged to inpatient rehab by
      hospital-day eight for the continuation of intravenous antibiotics. This case
      represents a frontal lobe abscess caused by the contiguous spread of
      Streptococcus anginosus from a frontal sinus infection. This is a relatively rare
      presentation of SAG infection in an immunocompetent patient. The case outlines
      the importance of imaging modality choice in the various stages of brain abscess
      formation, and the necessity of maintaining an index of suspicion for brain
      abscess in patients with few traditional risk factors and little to no history on
      presentation.

PMID- 29218261
TI  - Bilateral Occipital Lobe Hemorrhages Presenting as Denial of Blindness in
      Posterior Reversible Encephalopathy Syndrome- A Rare Combination of Anton
      Syndrome and Encephalopathy.
AB  - Posterior reversible encephalopathy syndrome (PRES) or reversible posterior
      leukoencephalopathy (RPL) is an acute neurological syndrome characterized by the
      development of radiological abnormalities on brain imaging along with clinical
      manifestations, such as a headache, seizures, encephalopathy, etc. We report the
      case of a middle-aged male who presented to the emergency department after he
      woke up with complete blindness and was found to have hemorrhagic PRES.
      Intracranial hemorrhages were seen in around 15% of patients who presented with
      this condition. In this article, we review the different types of hemorrhages
      seen in the setting of PRES and their associations.

PMID- 29218263
TI  - Research in imaging/biomarkers for precision medicine in lung cancer: National
      Cancer Institute funding opportunities.

PMID- 29218264
TI  - Role of PET/CT for precision medicine in lung cancer: perspective of the Society
      of Nuclear Medicine and Molecular Imaging.
AB  - This article discusses the role of PET/CT in contributing to precision medicine
      in lung cancer, and provides the perspective of the Society of Nuclear Medicine
      and Molecular Imaging (SNMMI) on this process. The mission and vision of SNMMI
      are listed, along with the guidance provided by SNMMI to promote best practice in
      precision medicine. Basic principles of PET/CT are presented. An overview of the
      use of PET/CT imaging in lung cancer is discussed. In lung cancer patients,
      PET/CT is vitally important for optimal patient management. PET/CT is essential
      in determining staging and re-staging of disease, detecting recurrent or residual
      disease, evaluating response to therapy, and providing prognostic information.
      PET/CT is also critically important in radiation therapy planning by determining
      the extent of active disease, including an assessment of functional tumor volume.
      The current approach in tumor imaging is a significant advance over conventional
      imaging. However, recent advances suggest that therapeutic response criteria in
      the near future will be based on metabolic characteristics and will include the
      evaluation of biologic characteristics of tumors to further enhance the
      effectiveness of precision medicine in lung cancer, producing improved patient
      outcomes with less morbidity.

PMID- 29218262
TI  - Neurologic Outcomes Following Care in the Pediatric Intensive Care Unit.
AB  - Purpose of review: With increasing survival of children requiring admission to
      pediatric intensive care units (PICU), neurodevelopmental outcomes of these
      patients are an area of increased attention. Our goal was to systematically
      review recently published literature on neurologic outcomes of PICU patients.
      Recent Findings: Decline in neurofunctional status occurs in 3%-20% of children
      requiring PICU care. This proportion varies based on primary diagnosis and
      severity of illness, with children admitted for primary neurologic diagnosis,
      children who suffer cardiac arrest or who require invasive interventions during
      the PICU admission, having worse outcomes. Recent research focuses on early
      identification and treatment of modifiable risk factors for unfavorable outcomes,
      and on long-term follow-up that moves beyond global cognitive outcomes and is
      increasingly including tests assessing multidimensional aspects of
      neurodevelopment. Summary: The pediatric critical care research community has
      shifted focus from survival to survival with favorable neurologic outcomes of
      children admitted to the PICU.

PMID- 29218265
TI  - The role of Imaging and Radiation Oncology Core for precision medicine era of
      clinical trial.
AB  - Imaging and Radiation Oncology Core (IROC) services have been established for the
      quality assurance (QA) of imaging and radiotherapy (RT) for NCI's Clinical Trial
      Network (NCTN) for any trials that contain imaging or RT. The randomized clinical
      trial is the gold standard for evidence-based medicine. QA ensures data quality,
      preventing noise from inferior treatments obscuring clinical trial outcome. QA is
      also found to be cost-effective. IROC has made great progress in multi
      institution standardization and is expected to lead QA standardization, QA
      science in imaging and RT and to advance quality data analysis with big data in
      the future. The QA in the era of precision medicine is of paramount importance,
      when individualized decision making may depend on the quality and accuracy of RT
      and imaging.

PMID- 29218266
TI  - Ensuring sample quality for blood biomarker studies in clinical trials: a
      multicenter international study for plasma and serum sample preparation.
AB  - Background: Sample quality is critical for biomarker detection in oncology, and
      platelet degradation and contamination in plasma have a remarkable impact on the
      ability to accurately quantify many blood-based biomarkers. Platelet factor 4
      (PF4) can be used as an indicator to monitor sample quality. This multicenter
      study aimed to determine the impact of critical components of the blood sample
      handling process on platelet degradation/contamination and to establish an
      optimal method for collecting platelet-poor plasma samples. Methods: At each of
      six participating centers, blood samples were drawn from 12-13 healthy
      volunteers. Serum and plasma samples were prepared from whole blood samples using
      nine different methods that have been commonly used in ongoing multicenter
      trials. PF4 levels in the prepared samples were measured by enzyme-linked
      immunosorbent assay (ELISA). Paired t-tests were used for statistical analysis.
      Results: Blood samples were collected from 74 subjects enrolled in six centers.
      PF4 levels were significantly higher in serum samples than in plasma samples
      (P<0.001), in plasma samples from blood that sat at room temperature for 5
      minutes (P=0.021), in plasma samples prepared at an insufficient centrifugal
      force (P<0.001), and in plasma samples prepared from blood that sat for longer
      than 4 hours on ice (P=0.001). For each method, the PF4 levels did not differ
      significantly among the centers or between Chinese and American subjects. The
      methods that resulted in normal levels of PF4 involved keeping blood samples on
      ice for 30 minutes to <4 hours and centrifugation at 2,500-3,000 *g for 30 min.
      Conclusions: This multicenter study evaluated multiple blood sample handling
      conditions for minimizing platelet degradation during plasma serum preparation
      and determined an optimal method for preparing platelet-poor plasma. The findings
      of this study can be applied in future blood biomarker studies.

PMID- 29218267
TI  - Radiomics in precision medicine for lung cancer.
AB  - With the improvement of external radiotherapy delivery accuracy, such as
      intensity-modulated and stereotactic body radiation therapy, radiation oncology
      has recently entered in the era of precision medicine. Despite these precise
      irradiation modalities, lung cancers remain one of the most aggressive human
      cancers worldwide, possibly because of diverse genotypic alterations that drive
      and maintain lung tumorigenesis. It has been long recognized that imaging could
      aid in the diagnosis, tumor delineation, and monitoring of lung cancer. Moreover,
      accumulating evidence suggests that imaging information could be further used to
      tailor treatment type and intensity, as well as predict treatment outcomes in
      radiotherapy. However, these imaging tasks have been carried out either
      qualitatively or using simplistic metrics that doesn't take advantage of the full
      scale of imaging knowledge. Radiomics, which is a recent field of research that
      aims to provide a more quantitative representation of imaging information
      relating tumor phenotypes to clinical and genotypic endpoints by embedding
      extracted image features into predictive mathematical models. These predictive
      models can be a key component in the clinician decision making and treatment
      personalization. This review provides an overview of the radiomics application
      and its methodology for radiation oncology studies in lung cancer.

PMID- 29218268
TI  - Blood-based tumor biomarkers in lung cancer for detection and treatment.
AB  - The therapeutic landscape of lung cancer has expanded significantly over the past
      decade. Advancements in molecularly targeted therapies, strategies to discover
      and treat resistance mutations, and development of personalized cancer treatments
      in the context of tumor heterogeneity and dynamic tumor biology have made it
      imperative to obtain tumor samples on several different occasions through the
      course of patient treatment. While this approach is critical to the delivery of
      optimal cancer treatment, it is fraught with a number of barriers including the
      need for invasive procedures with associated complications, access to limited
      amount of tissue, logistical delays in obtaining the biopsy, high healthcare
      cost, and in many cases inability to obtain tissue because of technically
      difficult location of the tumor. Given multiple limitations of obtaining tissue
      samples, the use of blood-based biomarkers ("liquid biopsies") may enable earlier
      diagnosis of cancer, lower costs by avoiding complex invasive procedures,
      tailoring molecular targeted treatments, improving patient convenience, and
      ultimately supplement clinical oncologic decision-making. In this paper, we
      review various blood-based biomarkers including circulating tumor cells (CTCs),
      circulating tumor DNA (ctDNA), tumor derived exosomes, tumor educated platelets
      (TEPs), and microRNA; and highlight current evidence for their use in detection
      and treatment of lung cancer.

PMID- 29218269
TI  - Blood-based biomarkers for precision medicine in lung cancer: precision radiation
      therapy.
AB  - Both tumors and patients are complex and models that determine survival and
      toxicity of radiotherapy or any other treatment ideally must take into account
      this variability as well as its dynamic state. The genetic features of the tumor
      and the host, and increasingly also the epi-genetic and proteomic
      characteristics, are being unraveled. Multiple techniques, including histological
      examination, blood sampling, measurement of circulating tumor cells (CTCs), and
      functional and molecular imaging, can be used for this purpose. However, the
      effects of radiation on the tumor and on organs at risk (OARs) are also
      influenced by the applied dose and volume of irradiated tissues. Combining all
      these biological, clinical, imaging, and dosimetric parameters in a validated
      prognostic or predictive model poses a major challenge. Here we aimed to provide
      an objective review of the potential of blood markers to guide high precision
      radiation therapy. A combined biological-mathematical approach opens new doors
      beyond prognostication of patients, as it allows truly precise oncological
      treatment. Indeed, the core for individualized and precision medicine is not only
      selection of patients, but even more the optimization of the therapeutic window
      on an individual basis. A holistic model will allow for determination of an
      individual dose-response relationship for each organ at risk for each tumor in
      each individual patient for the complete oncological treatment package. This
      includes, but is not limited to, radiotherapy alone. Individualized dose-response
      curves will allow for consideration of different doses of radiation and
      combinations with other drugs to plan for both optimal toxicity and complete
      response. Insights into the interactions between a multitude of parameters will
      lead to the discovery of new pathways and networks that will fuel new biological
      research on target discovery.

PMID- 29218270
TI  - Anatomic, functional and molecular imaging in lung cancer precision radiation
      therapy: treatment response assessment and radiation therapy personalization.
AB  - This article reviews key imaging modalities for lung cancer patients treated with
      radiation therapy (RT) and considers their actual or potential contributions to
      critical decision-making. An international group of researchers with expertise in
      imaging in lung cancer patients treated with RT considered the relevant
      literature on modalities, including computed tomography (CT), magnetic resonance
      imaging (MRI) and positron emission tomography (PET). These perspectives were
      coordinated to summarize the current status of imaging in lung cancer and flag
      developments with future implications. Although there are no useful randomized
      trials of different imaging modalities in lung cancer, multiple prospective
      studies indicate that management decisions are frequently impacted by the use of
      complementary imaging modalities, leading both to more appropriate treatments and
      better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT
      which is widely accepted to be the standard imaging modality for staging of lung
      cancer patients, for selection for potentially curative RT and for treatment
      planning. PET is also more accurate than CT for predicting survival after RT. PET
      imaging during RT is also correlated with survival and makes response-adapted
      therapies possible. PET tracers other than FDG have potential for imaging
      important biological process in tumors, including hypoxia and proliferation. MRI
      has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly
      developing technology with great potential for online monitoring and modification
      of treatment. The role of imaging in RT-treated lung cancer patients is evolving
      rapidly and will allow increasing personalization of therapy according to the
      biology of both the tumor and dose limiting normal tissues.

PMID- 29218272
TI  - Blood-based biomarkers in lung cancer: prognosis and treatment decisions.
AB  - Despite recent advances, non-small cell lung cancer (NSCLC) remains a devastating
      disease with overall poor prognosis. Major contributing factors include obstacles
      to diagnosing the disease early in its course during the asymptomatic stage as
      well as diversity and complexity of its biology underlying tumorigenesis and
      tumor progression. Advances in molecularly targeted therapies which drives the
      development of personalized cancer care require precise and comprehensive
      understanding of tumor biology, not only at the time of diagnosis but also during
      treatment course and surveillance. As lung tumor tissue can be difficult to
      obtain without invasive and potentially risky procedures, it is difficult to
      monitor treatment response with serial tissue biopsies. Development of non
      invasive but reliable blood based tumor markers has become an important research
      area. In this review, we focus on the following circulating biomarkers that have
      been identified in recent years: circulating tumor cells (CTCs); circulating cell
      free nucleic acids, such as circulating tumor DNA (ctDNA) and microRNA (miR); and
      other biomarkers such as genomic and proteomic features. These biomarkers not
      only have prognostic values, but also can help guild treatment decisions by
      monitoring tumor burden, detecting minimal residual disease and/or recurrent
      disease, as well as monitoring evolution of genetic alterations throughout the
      treatment course.

PMID- 29218273
TI  - Potential future consideration for imaging and blood-based biomarkers for
      precision medicine in lung cancer.

PMID- 29218271
TI  - Magnetic resonance imaging in precision radiation therapy for lung cancer.
AB  - Radiotherapy remains the cornerstone of curative treatment for inoperable locally
      advanced lung cancer, given concomitantly with platinum-based chemotherapy. With
      poor overall survival, research efforts continue to explore whether integration
      of advanced radiation techniques will assist safe treatment intensification with
      the potential for improving outcomes. One advance is the integration of magnetic
      resonance imaging (MRI) in the treatment pathway, providing anatomical and
      functional information with excellent soft tissue contrast without exposure of
      the patient to radiation. MRI may complement or improve the diagnostic staging
      accuracy of F-18 fluorodeoxyglucose position emission tomography and computerized
      tomography imaging, particularly in assessing local tumour invasion and is also
      effective for identification of nodal and distant metastatic disease.
      Incorporating anatomical MRI sequences into lung radiotherapy treatment planning
      is a novel application and may improve target volume and organs at risk
      delineation reproducibility. Furthermore, functional MRI may facilitate dose
      painting for heterogeneous target volumes and prediction of normal tissue
      toxicity to guide adaptive strategies. MRI sequences are rapidly developing and
      although the issue of intra-thoracic motion has historically hindered the quality
      of MRI due to the effect of motion, progress is being made in this field. Four
      dimensional MRI has the potential to complement or supersede 4D CT and 4D F-18
      FDG PET, by providing superior spatial resolution. A number of MR-guided
      radiotherapy delivery units are now available, combining a radiotherapy delivery
      machine (linear accelerator or cobalt-60 unit) with MRI at varying magnetic field
      strengths. This novel hybrid technology is evolving with many technical
      challenges to overcome. It is anticipated that the clinical benefits of MR-guided
      radiotherapy will be derived from the ability to adapt treatment on the fly for
      each fraction and in real-time, using 'beam-on' imaging. The lung tumour site
      group of the Atlantic MR-Linac consortium is working to generate a challenging MR
      guided adaptive workflow for multi-institution treatment intensification trials
      in this patient group.

PMID- 29218274
TI  - Demographic Characteristics of Patients Undergoing Rhinoplasty: A Single Center
      Two-Time-Period Comparison.
AB  - BACKGROUND: One of the most common cosmetic surgeries is rhinoplasty. Iran has
      the highest rate of rhinoplasty, worldwide. The aim of this study was to compare
      the demographic characteristics of patients' undergone rhinoplasty during two
      time-period with a 10-year-interval in a single surgical center in Isfahan, Iran.
      METHODS: In a retrospective study, data of the patients who were scheduled for
      elective rhinoplasty including their age and gender in two-time-period (2005 and
      2015) were collected and compared. RESULTS: Data of the 470 and 472 patients'
      undergone elective primary rhinoplasty during 2005 and 2015 were collected,
      respectively. In 2005, the age range of patients was 16-51 years. Frequency of
      patients aged less than 20 years and more than 40 years was 27.1% and 3%,
      respectively. In 2015, the age range of patients was 16-59 years. Frequency of
      patients aged less than 20 years and more than 40 years was 12.9% and 5.6%,
      respectively. Patients in the two studied periods were similar regarding gender,
      but the mean age of patients had a significant increase during the time.
      CONCLUSION: Most of our patients were female and the female to male ratio was
      similar in two studied periods, but it seems that rhinoplasty request is higher
      in older age in recent years. It is recommended to plan a trend study and more
      studies considering other factors to be effective in epidemiologic feature of
      rhinoplasty in our community.

PMID- 29218275
TI  - Outcomes of Surgical Excision and Brachytherapy in Intractable Keloids.
AB  - BACKGROUND: Keloids as unusual scars are injury remnants characterized by bizarre
      cosmetics and painful itching. This study assessed outcomes of surgical excision
      and brachytherapy in intractable keloids. METHODS: Six patients with 10 keloid
      lesions were followed up. Surgical excision was done with 1-2 mm margin, and then
      radiotherapy was undertaken in 3 divided fractions on days 0, 1 and 2 after
      surgery. Scar improvement was evaluated by patients and observer with scar
      assessment scale (POSAS). RESULTS: Median age of patients was 38.3+/-6.4, while
      40% were male and 60% were female. The mean primary size of the lesion before
      brachytherapy was 325.18+/-426.16 mm2 and the median size was 153.48 mm2. The
      mean primary size of the lesions with recurrence before brachytherapy was
      150.50+/-124.78 mm2. The clinical improvement of the scars with POSAS scoring by
      the observer was 17.1+/-3.2 and by the patients was 20.8+/-11.5. In 5 patients
      who were evaluated, two keloid lesions showed recurrence (20%), and 8 lesions had
      no recurrence (80%). No patients reported side effects, but only one patient, a
      43 years old woman with 5 keloid lesions, suffered wound infection and local
      dehiscence of the wound, followed by the second session of brachytherapy. The
      average time of relapse was 26.3+/-0.9 months. CONCLUSION: The use of surgical
      resection in combination with brachytherapy was demonstrated as a modality for
      treatment of refractory keloid scars that can be recommended to surgeons who deal
      with these patients.

PMID- 29218276
TI  - Role of Square Flap in Post Burn Axillary Contractures.
AB  - BACKGROUND: Post-burn contractures are a commonly encountered problem and many
      techniques have been described in their treatment. Z-plasties are the commonest
      local flap procedure done for linear bands with adjacent healthy tissue. Our aim
      was to assess the use of square flap technique in axillary contractures. METHODS:
      Ten patients with type I and II axillary contractures underwent release by the
      square flap technique. All cases were followed up for at least one year and
      analysed for range of motion and aesthetic outcome. RESULTS: All cases achieved
      full range of movement postoperatively with no recurrence during follow up period
      and a good cosmetic outcome. CONCLUSION: Square flap was shown to be a reliable
      technique for mild to moderate axillary contractures of the anterior or posterior
      axillary folds even when there is significant adjacent scarring of chest wall or
      back of types I and II.

PMID- 29218277
TI  - Effect of Multimedia Self-Care Education on Quality of Life in Burn Patients.
AB  - BACKGROUND: Burn injuries can have adverse effects on quality of life of patients
      and can disturb their physiological, psychological, social and spiritual well
      being. This study aimed to investigate the effect of multimedia self-care program
      on quality of life in burn patients. METHODS: This Randomized controlled clinical
      trial was conducted from November 2015 to December 2016. The samples were
      hospitalized burn patients with 10% to 45% of 1st, 2nd and 3rd degree burns of
      total body surface area (TBSA). The patients were randomly allocated into
      experimental (n=50) and control (n=50) groups. Both groups received the routine
      in-person self-care trainings of the hospital and then the experimental group
      received self-care compact disks. The quality of life questionnaire in both
      groups were completed before intervention and after 3-months and statistically
      analyzed. RESULTS: Accordingly, the changes in quality of life and the dimensions
      between both groups after 3 month of intervention were significant. The changes
      in quality of life in experiment group was significantly greater than control
      group for physical, psychological and social variables. CONCLUSION: According to
      the findings, using multimedia self-care programs can improve burn patient's
      quality of life, so it is recommended for nurses and hospital staffs of burn
      injury wards to use multimedia self-care programs as a complementary therapy
      measure.

PMID- 29218278
TI  - Evaluation of Subclinical Extension of Basal Cell Carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy with
      increasing incidence worldwide. The tumor invades surrounding tissues in an
      irregular pattern via subclinical and microscopic finger-like growths known as
      subclinical extension. Subclinical extension may be responsible for incomplete
      resection of the tumor. This study investigates the subclinical extension of BCC.
      METHODS: In a retrospective study for evaluation of subclinical extension of BCC,
      Patients' demographic data and characteristics (disease duration, location, size,
      and history of radiotherapy) were documented. Pathology samples were assessed in
      terms of histological type, subclinical extension, depth, and involvement of
      margins. RESULTS: The study was conducted on 102 pathological samples of 84
      patients (49 males, 35 females) with BCC. The mean age was 65.4+/-12.55 years.
      Overall, 83% of pathology samples had subclinical extension. Subclinical
      extension had no correlation with lesion size (p=0.591; r=0.056), but had a
      direct correlation with lesion depth (p=0.033; r=0.220). Resection of the tumor
      with a margin of 5.5 mm eliminated the entire lesion and its subclinical
      extension area with a confidence rate of 95%. CONCLUSION: Based on this study,
      resection of BCC lesions with a margin of 5.5 mm will eradicate the whole lesion
      including the subclinical extension area with 95% confidence rate. Depth of the
      tumor, not its size or histologic subtype, affects the required margin of
      excision.

PMID- 29218279
TI  - Non-metastatic Non-melanoma Skin Cancers: Our 3 Years of Clinical Experiences.
AB  - BACKGROUND: Nonmelanoma skin cancers (NMSC) constitute the largest group of skin
      cancers. In this study, NMSCs were analyzed retrospectively. METHODS: Between
      June 2013 and March 2017, demographics and comorbidities of patients underwent
      reconstructive surgery for NMSC; their risk factors, types, diameters,
      differentiation, localizations, follow-up times, treatment methods and
      complications were compared and statistically analyzed. RESULTS: Totally, 163
      tumors [111 basal cell carcinoma and 52 cutaneous squamous cell carcinoma (cSCC)]
      were excized from 148 patients (63 females, 85 males). Mean age was 70.8 years.
      Fitzpatrick skin types were between 2-4 and 74 patients. Comorbidities were
      detected in 63 patients. Tumors were mostly localized in head and neck regions.
      Forty two lesions in cSCC group were good and 10 were medium differentiated.
      Defects were reconstructed with flaps in 108 patients. Others underwent primer
      suturation and grafting. Mean follow-up time was 16.2 months. There was not any
      complication except one graft failure. There were not significant statistical
      differences between two groups in terms of skin type, comorbidity, tumor size,
      fallow-up time and gender values. Conversely, differences of risk factor and age
      values between the groups were significant. There was a positive correlation
      between the tumor diameter and poor differentiation in cSCC group. Moreover,
      there was a negative correlation between tumor size and skin type values in
      groups. CONCLUSION: Our results are quite different from literature needing
      further multicentric studies on NMSC to clarify the difference.

PMID- 29218280
TI  - The Effect of Lithospermum officinale, Silver Sulfadiazine and Alpha Ointments in
      Healing of Burn Wound Injuries in Rat.
AB  - BACKGROUND: Burn is the most devastating condition in emergency medicine leading
      to chronic disabilities. This study aimed to compare the effect of Lithospermum
      officinale, silver sulfadiazine and alpha ointments on healing of burn wounds in
      rat. METHODS: Ninety-five rats were divided into 5 groups. Group 1 just underwent
      burn injury, and groups 2-5 received alpha ointment, silver sulfadiazine (SSD),
      gel base and L. officinale extract, respectively. A hot plate was used for
      induction of a standard 3rd degree burn wound. Burn wounds were macroscopically
      and microscopically evaluated on days 7th, 14th and 21st after burn induction.
      RESULTS: A decrease in the number of inflammatory cells was noted when L.
      officinale and SSD were applied while the most inflammatory response was seen
      after administration of alpha ointment. The number of macrophages alone decreased
      after burn injury, while the frequency was the most when L. officinale and alpha
      ointment were applied. Re-epithelialization, angiogenesis and formation of
      granulation tissue were the best in relation to L. officinale and alpha ointment
      while, the worst results belonged to burn injury group and SSD regarding
      granulation tissue formation. Considering histological assessment, the best
      results were observed for scoring of inflammation, re-epithelialization,
      angiogenesis, formation of granulation tissue and number of macrophage when L.
      officinale and alpha ointment were used after burn injury. CONCLUSION: It can be
      concluded that topical application of L. officinale as a non-toxic, inexpensive
      and easy to produce herbal can lead to a rapid epithelialization and wound
      healing and these findings can be added to the literature on burn wound healing.

PMID- 29218281
TI  - Palate Mucoperosteum: An Usefull Adjunct in Buccal Mucosa Reconstruction.
AB  - Background: Palate is a complex structure separating oro- and nasopharynx.
      However, reconstruction of the defects of palate is much simpler because of the
      versatile mucoperiosteal flaps. Here, we present our experience of palatal
      mucoperiosteal flap used in different situations. Methods: Fifteen patients of
      palatal as well as buccal mucosa defects were reconstructed using either free or
      pedicled mucoperiosteum. Results: All patients recovered well. No flap loss or
      secondary procedure were required. Conclusion: Success in Reconstruction of the
      palatal defects depends on creation of good nasal as well as buccal mucosal
      lining. The rich vascular macronet in the palatal mucosa makes it an ideal donor
      site for local reconstruction. The mucoperiosteum harvested either as a free
      graft or as pedicled flap serves the purpose well leaving no donor site
      deformity.

PMID- 29218282
TI  - Which Tissue Should Be Removed in Upper Blepharoplasty? Analysis and Evaluation
      of Satisfaction.
AB  - BACKGROUND: Due to various options for tissue resection and preoperative
      markings, many different reports on aesthetics and patient's satisfaction exist.
      To assess differences among tissue resections and risk factors, we herein
      analyzed satisfaction levels of patients that underwent upper blepharoplasty.
      METHODS: A retrospective analysis during the period from January 2006 to June
      2013 was conducted by reviewing patient's electronic medical files. All patients
      underwent medically indicated upper blepharoplasty at our department. We
      classified patients relating to resected tissues; hence the categories created
      were skin, skin/muscle, skin/muscle/fat and skin/fat. Furthermore, an evaluation
      of risk factors according to the patient's number of present medical
      preconditions ranging from 0 (none) to 4 was performed. Data collection was
      conducted by reviewing patient's electronic medical files. Moreover, a
      questionnaire concerning patient's satisfaction was forwarded. RESULTS: No
      significant differences in patient's satisfaction and complication rates
      comparing the different groups of tissue resection were noted. However, we found
      a significantly higher complication rate at a presence of 2 risk factors. In
      addition, a significantly worse scar outcome and longer recovery periods in
      patients with 4 risk factors were observed. CONCLUSION: The extent of tissue
      resection has no statistically quantifiable effect on patient's satisfaction
      ratings and complications. For this reason, we believe cautious resection of
      muscle and fat is only indicated if pathologies are present. Moreover, patients
      with 2 risk factors or more shall be rigorously evaluated preoperatively to avoid
      complicating events.An abbreviated form of this manuscript was presented at the
      conjoint 52nd and 45th annual meeting of the Austrian and German Society of
      Plastic, Aesthetic and Reconstructive Surgery, September 11th-13th 2014 in
      Munich, Germany.

PMID- 29218283
TI  - Early Reconstructions of Complex Lower Extremity Battlefield Soft Tissue Wounds.
AB  - BACKGROUND: Severe lower extremity trauma as a devastating combat related injury
      is on the rise and this presents reconstructive surgeons with significant
      challenges to reach optimal cosmetic and functional outcomes. This study assessed
      early reconstructions of complex lower extremity battlefield soft tissue wounds.
      METHODS: This was a prospective case series study of battled field injured
      patients which was done in the Department of Plastic Surgery, Baqiyatallah
      University of Medical Sciences hospitals, Tehran, Iran between 2013-2015. In this
      survey, 73 patients were operated for reconstruction of lower extremity soft
      tissue defects due to battlefield injuries. RESULTS: Seventy-three patients (65
      men, 8 womens) ranging from 21-48 years old (mean: 35 years) were enrolled. Our
      study showed that early debridement and bone stabilization and later coverage of
      complex battlefields soft tissue wounds with suitable flaps and grafts of lower
      extremity were effective method for difficult wounds managements with less
      amputation and infections. CONCLUSION: Serial debridement and bone stabilization
      before early soft tissue reconstruction according to reconstructive ladder were
      shown to be essential steps.

PMID- 29218284
TI  - How Much Can We do by Reverse Superficial Sural Artery Flap to Potentiate Its
      Effects: Introducing Spout Sural Flap as a New Modification.
AB  - BACKGROUND: Due to shortage of local donor tissue and unreliable blood supply,
      free flaps were the mainstay of treatment for tissue defects in the lower leg and
      foot region, but it requires a qualified microvascular surgeon. Recently,
      attention has been paid to reverse superficial sural artery flap (RSSAF) and its
      modifications as a good alternative to pave the way to simple and friendly
      techniques. METHODS: Excluding each patient with septic and severely ischemic
      foot, every patient with tissue defect in distal leg and proximal foot region
      were studied. Various methods were applied including spout technique with
      sufficient follow up. No imaging was used to evaluate the blood supply. RESULTS:
      Five patients underwent spout technique with excellent results in four cases.
      Spout technique in one case failed due to narrow base. In five cases, RSSAF was
      performed with creating skin tunnel and very good results. CONCLUSION: RSSAF is a
      good alternative for free flap to cover the leg and foot tissue defects. We also
      advise wide base pedicle (>4 cm) in every patient.

PMID- 29218285
TI  - Efficacy of Digital Anesthesia: Comparison of Two Techniques.
AB  - BACKGROUND: Digital nerve block is commonly performed by care providers in
      medical fields. This study compares the blocks in terms of effectiveness of
      anesthesia and pain. METHODS: Patients were divided into two groups. First group
      underwent digital block whereas 2nd group had transmetacarpal digital block. The
      subcutaneous ring block was performed by two injections of 3 ml of 2% lignocaine
      in a 3 ml syringe with a 26G needle at the level of phalangeal/palmer crease. One
      prick was performed on either side of the finger base extending on dorsal and
      volar aspects of the digit. The transmetacarpal block received lignocaine
      identically at dorsal aspect of metacarpo-phalangeal joint. 1.5ml of the solution
      was injected in dorsal and 1.5ml in palmer side on either side of the finger.
      When sensation of needle was felt, 1ml of the solution was injected. Then the
      needle was withdrawn injecting another 1ml and finally the last 1ml was injected
      close to the dorsal skin. The pain prick was recorded after 30 seconds. RESULTS:
      The mean time to complete abolition of sensation was 9.1 minutes in group I and
      9.0 minutes in group II. The mean duration of anaesthesia was 202 minutes in
      group I and 206.8 minutes in group II. The mean pain scale was 5.67 (range=4-7)
      in group I and 4.2 (range=3-7) in group II. CONCLUSION: Subcutaneous ring block
      and transmetacarpal techniques are good in digital anesthesia and involve the
      administration of the local anaesthetic through two injections.

PMID- 29218286
TI  - Experience of Breast Augmentation in Pakistani Females.
AB  - BACKGROUND: Breast augmentation is an elective surgery used to increase the size
      of the breast in females. This study was undertaken to determine the breast
      augmentation in Pakistani females. METHODS: From 2006 to 2011, 43 female patients
      who underwent breast augmentation via infra-mammary, periareolar, trans-umbilical
      and fat transfer were enrolled. For augmentation, saline-filled or gel-filled
      implants were used in the supine position under general anesthesia and local
      infiltration of adrenaline (1:100,000 dilution) on each side. After the surgery,
      postoperative dressing was changed after 3-5 days and post-op bra was used for
      next 3-4 weeks. The patients were followed up for any complications too. RESULTS:
      The majority of patients (60.4%) were less than 30 years (mean age: 27.51 years).
      Most of patients (70%) had infra-mammary incision, 13.9% had periareolar, 9.3%
      had trans-umbilical and 4.7% had fat transfer. Saline-filled implants were used
      in 30.2%, whereas gel-filled implants in 69.8% of patients. Implant volume in
      infra-mammary, periareolar, trans-umbilical and fat transfer approaches was
      278.9, 291.7, 277.5 and 325 mL, respectively. Only two cases of infection were
      recorded in early postop period. One patient responded to conservative treatment
      and in 2nd patient, implants were removed. There was only one case of
      hypertrophic scar. No case of capsular contracture was seen. Quality of scar was
      satisfactory in infra-mammary and periareolar incisions. Changes in sensations
      were noted in 6 cases, 4 of them had periareolar incision. CONCLUSION: Properly
      performed breast augmentation results in restoration of physical and
      psychological well-being of the patient and less complication rates.

PMID- 29218287
TI  - Use of Forehead Flap for Nasal Tip Reconstruction after Traumatic Nasal
      Amputation.
AB  - Nose is one of the most important aesthetic unit of the face.Management of nasal
      trauma plays a significant role in the practices of the majority of facial and
      reconstructive surgeons. Replantation, although technically very challenging, is
      undoubtedly the procedure of choice following traumatic nasal amputation. Here we
      present an illustrative case report of the traumatic amputation of a nasal tip
      that was treated successfully with a paramedian forehead flap and further nasal
      reconstructive surgery. Use of the forehead flap was performed five hours after
      the occurrence of trauma and was followed by surgical repair about three weeks
      later. This case presents evidence that a forehead flap as a full-thickness
      composite graft can survive with an acceptable clinical outcome. In this
      particular case, the final result was satisfactory.

PMID- 29218288
TI  - Giant Anterior Neck Lipoma with Bleeding Pressure Ulcer in an Elderly Man: A Rare
      Entity.
AB  - Giant lipomas are benign soft tissue tumors found rarely in the neck and are
      still rarer in the anterior part of the neck. A 70-year-old male patient was
      presented with a huge swelling measuring 35 cm in maximum dimension, in the front
      of the neck, reaching up till the umbilicus. The swelling was painless, slow
      growing and acquired the huge size in approximately 20 years. Ultrasound and CT
      scan findings were suggestive of a soft tissue lesion. Fine needle aspiration
      cytology yielded mature adipose tissue fragments. A complete surgical removal of
      the mass was done which on gross examination, measured 32 cms in longest diameter
      and weighed 2500 grams. Diagnosis of giant anterior neck lipoma with pressure
      ulcer was confirmed on histopathology. We described a case of excessively large
      lipoma of anterior neck, which is the largest anterior neck lipoma with pressure
      ulcer reported till date.

PMID- 29218289
TI  - Craniofacial Fibrous Dysplasia of Zygomaticomaxillary Complex.
AB  - Fibrous dysplasia is a benign bone disease first described by Lichtenstein in
      1938. It is characterized by progressive replacement of normal bone with fibro
      osseous connective tissue. When the disease involves craniofacial skeleton, it
      results in significant disfigurement and other functional problems. This paper
      reports a case of large craniofacial fibrous dysplasia involving
      zygomaticomaxillary complex in a 24-year old male patient. Clinical presentation
      and imaging characteristics of the pathology is discussed in detail. The disease
      caused significant facial asymmetry which was satisfactorily managed by surgical
      recontouring.

PMID- 29218290
TI  - Critical Upper Limb Ischemia Due to Brachial Tourniquet in Misdiagnosed Thoracic
      Outlet Syndrome after Carpal Tunnel Decompression: A Case Report.
AB  - We present the case of a 68-year-old woman, referred to our department for
      critical upper limb ischemia, which had occurred a few days after homolateral
      surgical ligamentotomy for carpal tunnel syndrome, diagnosed and confirmed by
      electromyography, and performed with a brachial tourniquet. The patient was later
      admitted for subsequent progressive necrosis of the first three fingers of the
      left hand, accompanied by signs of upper limb ischemia. An accessory cervical rib
      was identified, completely obliterating the subclavian artery distally at the
      origin of the suprascapular artery. A complete humeral artery occlusion was also
      found at the middle third of the humerus. The accessory rib was resected and the
      subclavian artery recanalized. A few days later, necrosis of the distal third of
      the first two fingers appeared and surgical resection was performed. Despite this
      chronic condition, the acute occlusion of collateral circles was probably induced
      by the brachial tourniquet. This represents a rare event, never previously
      reported in the literature: a case of critical upper limb ischemia due to a
      brachial tourniquet in a patient with misdiagnosed thoracic outlet syndrome.
      Until specific electrophysiological criteria for this syndrome can be found,
      attention should focus on history and clinical examination in patients with
      suspected carpal tunnel syndrome.

PMID- 29218291
TI  - Congenital Bilateral Multiple Trigger Fingers in A 5-Year-Old Child.
AB  - Paediatric bilateral multiple trigger fingers are extremely rare. The underlying
      etiopathogenesis and hence the surgical principles of management of trigger
      finger in children are different from those of pediatric trigger thumb and adult
      trigger finger. In this paper, we report the case of a 5 year old girl with
      congenital trigger digits involving the middle, ring and little fingers of both
      hands. She did not have any episode of trauma, viral or bacterial infections or
      any metabolic disorder. Following lack of any improvement with a physiotherapy
      and a splintage regime for 6 weeks, we offered surgical management for the
      affected digits. Release was done in step-wise pattern. We present the
      intraoperative findings and surgical management of congenital trigger finger.

PMID- 29218292
TI  - Primary One Stage Reconstruction in Complex Facial Avulsion Injury.
AB  - Complex facial injuries with soft tissue degloving and bony avulsion are very
      devastating to the patient. Partial degloving injuries are described but
      hemifacial degloving with zygoma avulsion are rare. The author presents a case of
      post-traumatic degloving of the left upper lip, nose, part of forehead, upper and
      lower eyelids and cheek with avulsion of the left zygoma. The management included
      immediate resuscitation and early surgery to reposition the skeletal as well as
      soft tissue avulsion. The wound was thoroughly washed and primary repositioning
      and fixation were done. Early one stage surgery with meticulous debridement and
      alignment of the anatomical landmarks results in very good aesthetic and
      functional outcome.

PMID- 29218293
TI  - Acral Hypomelanocytic Melanoma of Left Great Toe: A Rare Cancer.

PMID- 29218294
TI  - Modifying "Pico" Question into "Picos" Model for More Robust and Reproducible
      Presentation of the Methodology Employed in A Scientific Study.

PMID- 29218295
TI  - Absence of the Labiomental Groove: A Common but Preventable Unpleasant Aesthetic
      Problem of the Lower Lip-Chin Burn Reconstruction.

PMID- 29218296
TI  - Evaluating Youtube as A Source of Patient Information on Dupuytren's Disease.

PMID- 29218297
TI  - Median Nerve Lipofibrohamartoma: A Treatment Dilemma.

PMID- 29218298
TI  - Digital Necrosis: A Hoarder's Tale.

PMID- 29218299
TI  - Editorial: Controversies and Perspectives in the Use of Postoperative
      Radiotherapy for Prostate Cancer.

PMID- 29218301
TI  - Long-term Outcomes after Salvage Stereotactic Radiosurgery (SRS) following In
      Field Failure of Initial SRS for Brain Metastases.
AB  - Purpose: The optimal treatment strategy following local recurrence after
      stereotactic radiosurgery (SRS) remains unclear. While upfront SRS has been
      extensively studied, few reports focus on outcomes after retreatment. Here, we
      report the results following a second course of SRS for local recurrence of brain
      metastases previously treated with SRS. Methods: Using institutional database,
      patients who received salvage SRS (SRS2) following in-field failure of initial
      SRS (SRS1) for brain metastases were identified. Radionecrosis and local failure
      were defined radiographically by MRI following SRS2. The primary endpoint was
      defined as the time from SRS2 to the date of all-cause death or last follow-up
      [overall survival (OS)]. The secondary endpoints included local failure-free
      survival (LFFS) and radionecrosis-free survival, defined as the time from SRS2 to
      the date of local failure or radionecrosis, or last follow-up, respectively.
      Results: Twenty-eight patients with 32 brain metastases were evaluated between
      years 2004 and 2015. The median interval between SRS1 and SRS2 was 9.7 months.
      Median OS was 22.0 months. Median LFFS time after SRS2 was 13.6 months. The
      overall local control rate following SRS2 was 84.4%. The 1- and 2-year local
      control rates are 88.3% (95% CI, 76.7-100%) and 80.3% (95% CI, 63.5-100%),
      respectively. The overall rate of radionecrosis following SRS2 was 18.8%. On
      univariate analysis, higher prescribed isodose line (p = 0.033) and higher gross
      tumor volume (p = 0.015) at SRS1 were associated with radionecrosis. Although not
      statistically significant, there was a trend toward lower risk of radionecrosis
      with interval surgical resection, fractionated SRS, lower total EQD2 (<50 Gy),
      and lack of concurrent systemic therapy at SRS2. Conclusion: In select patients,
      repeat LINAC-based SRS following recurrence remains a reasonable option leading
      to long-term survival and local control. Radionecrosis approaches 20% for high
      risk individuals and parallels historic values.

PMID- 29218302
TI  - Canine Soft Tissue Sarcomas: Can Being a Dog's Best Friend Help a Child?
AB  - Soft tissue sarcomas (STSs) remain a therapeutic challenge for pediatric and
      adolescent and young adult (AYA) patients. Still today, surgery, radiation
      therapy, and chemotherapy remain the mainstay of treatment. Obstacles in
      developing new treatment approaches to improve the outcome are: few patients to
      enroll in clinical trials, and the diversity of tumor biology between histologic
      subtypes. Pet dogs may offer an additional strategy to discover and test new
      therapeutic avenues. The number of dogs diagnosed with a STS each year in the
      United States is estimated to be around 27,000 to 95,000. In comparison,
      approximately 900 children less than 20 years old and 1,500 AYAs between 15 and
      29 years old are diagnosed with a STS each year in the United States. The
      mainstay for treatment of STSs in dogs is also surgery, with radiation therapy
      and chemotherapy when necessary. Similar to what is seen in humans, grade and
      stage are prognostic in dogs. In one comparative study of the histology and
      immunohistochemistry of canine STSs, most tumors were diagnosed as the human
      equivalent of undifferentiated sarcoma, spindle cell sarcoma, or unclassified
      spindle cell sarcoma. But much work remains to be done to fully assess the
      validity of canine STSs as a model. Gene expression analysis has been done in a
      limited number of canine STSs. Tissue banking, development of cell lines, and the
      ability to mobilize large-scale clinical trials will become essential in
      veterinary medicine to benefit both dogs and humans.

PMID- 29218300
TI  - The Dual Role of Cellular Senescence in Developing Tumors and Their Response to
      Cancer Therapy.
AB  - Cellular senescence describes an irreversible growth arrest characterized by
      distinct morphology, gene expression pattern, and secretory phenotype. The final
      or intermediate stages of senescence can be reached by different genetic
      mechanisms and in answer to different external and internal stresses. It has been
      maintained in the literature but never proven by clearcut experiments that the
      induction of senescence serves the evolutionary purpose of protecting the
      individual from development and growth of cancers. This hypothesis was recently
      scrutinized by new experiments and found to be partly true, but part of the gene
      activities now known to happen in senescence are also needed for cancer growth,
      leading to the view that senescence is a double-edged sword in cancer
      development. In current cancer therapy, cellular senescence is, on the one hand,
      intended to occur in tumor cells, as thereby the therapeutic outcome is improved,
      but might, on the other hand, also be induced unintentionally in non-tumor cells,
      causing inflammation, secondary tumors, and cancer relapse. Importantly,
      organismic aging leads to accumulation of senescent cells in tissues and organs
      of aged individuals. Senescent cells can occur transiently, e.g., during
      embryogenesis or during wound healing, with beneficial effects on tissue
      homeostasis and regeneration or accumulate chronically in tissues, which
      detrimentally affects the microenvironment by de- or transdifferentiation of
      senescent cells and their neighboring stromal cells, loss of tissue specific
      functionality, and induction of the senescence-associated secretory phenotype, an
      increased secretory profile consisting of pro-inflammatory and tissue remodeling
      factors. These factors shape their surroundings toward a pro-carcinogenic
      microenvironment, which fuels the development of aging-associated cancers
      together with the accumulation of mutations over time. We are presenting an
      overview of well-documented stress situations and signals, which induce
      senescence. Among them, oncogene-induced senescence and stress-induced premature
      senescence are prominent. New findings about the role of senescence in tumor
      biology are critically reviewed with respect to new suggestions for cancer
      therapy leveraging genetic and pharmacological methods to prevent senescence or
      to selectively kill senescent cells in tumors.

PMID- 29218303
TI  - Dynamic Regimes of El Nino Southern Oscillation and Influenza Pandemic Timing.
AB  - El Nino southern oscillation (ENSO) dynamics has been shown to drive seasonal
      influenza dynamics. Severe seasonal influenza epidemics and the 2009-2010
      pandemic were coincident with chaotic regime of ENSO dynamics. ENSO dynamics from
      1876 to 2016 were characterized to determine if influenza pandemics are coupled
      to chaotic regimes. Time-varying spectra of southern oscillation index (SOI) and
      sea surface temperature (SST) were compared. SOI and SST were decomposed to
      components using the algorithm of noise-assisted multivariate empirical mode
      decomposition. The components were Hilbert transformed to generate instantaneous
      amplitudes and phases. The trajectories and attractors of components were
      characterized in polar coordinates and state space. Influenza pandemics were
      mapped to dynamic regimes of SOI and SST joint recurrence of annual components.
      State space geometry of El Ninos lagged by influenza pandemics were characterized
      and compared with other El Ninos. Timescales of SOI and SST components ranged
      from sub-annual to multidecadal. The trajectories of SOI and SST components and
      the joint recurrence of annual components were dissipative toward chaotic
      attractors. Periodic, quasi-periodic, and chaotic regimes were present in the
      recurrence of trajectories, but chaos-chaos transitions dominated. Influenza
      pandemics occurred during chaotic regimes of significantly low transitivity
      dimension (p < 0.0001). El Ninos lagged by influenza pandemics had distinct state
      space geometry (p < 0.0001). Chaotic dynamics explains the aperiodic timing, and
      varying duration and strength of El Ninos. Coupling of all influenza pandemics of
      the past 140 years to chaotic regimes of low transitivity indicate that ENSO
      dynamics drives influenza pandemic dynamics. Forecasts models from ENSO dynamics
      should compliment surveillance for novel influenza viruses.

PMID- 29218304
TI  - From Invention to Innovation: Risk Analysis to Integrate One Health Technology in
      the Dairy Farm.
AB  - Current Hazard Analysis Critical Control Points (HACCP) approaches mainly fit for
      food industry, while their application in primary food production is still
      rudimentary. The European food safety framework calls for science-based support
      to the primary producers' mandate for legal, scientific, and ethical
      responsibility in food supply. The multidisciplinary and interdisciplinary
      project ALERT pivots on the development of the technological invention (BEST
      platform) and application of its measurable (bio)markers-as well as scientific
      advances in risk analysis-at strategic points of the milk chain for time and cost
      effective early identification of unwanted and/or unexpected events of both
      microbiological and toxicological nature. Health-oriented innovation is complex
      and subject to multiple variables. Through field activities in a dairy farm in
      central Italy, we explored individual components of the dairy farm system to
      overcome concrete challenges for the application of translational science in real
      life and (veterinary) public health. Based on an HACCP-like approach in animal
      production, the farm characterization focused on points of particular attention
      (POPAs) and critical control points to draw a farm management decision tree under
      the One Health view (environment, animal health, food safety). The analysis was
      based on the integrated use of checklists (environment; agricultural and
      zootechnical practices; animal health and welfare) and laboratory analyses of
      well water, feed and silage, individual fecal samples, and bulk milk. The
      understanding of complex systems is a condition to accomplish true innovation
      through new technologies. BEST is a detection and monitoring system in support of
      production security, quality and safety: a grid of its (bio)markers can find
      direct application in critical points for early identification of potential
      hazards or anomalies. The HACCP-like self-monitoring in primary production is
      feasible, as well as the biomonitoring of live food producing animals as sentinel
      population for One Health.

PMID- 29218305
TI  - Editorial: Continuous Quality Improvement (CQI)-Advancing Understanding of
      Design, Application, Impact, and Evaluation of CQI Approaches.

PMID- 29218306
TI  - Adolescents' Responses to a School-Based Prevention Program Promoting Healthy
      Eating at School.
AB  - Background: To improve the effectiveness of school-based programs that aim to
      promote adolescents' healthy food choices, it is essential to understand the
      views and behaviors of the target group. This study aimed to get a better
      understanding of adolescents' food and health perceptions and their willingness
      to be involved in a specific school-based prevention program, i.e., the Dutch
      "Healthy School Canteen Program." Methods: This study used a mixed-methods
      research design. First, seven semi-structured focus groups were conducted using a
      selective sample of 42 Dutch adolescents (25 girls, 17 boys, aged 13-16 years).
      Second, an online survey among 133 adolescent respondents (72 girls, 61 boys,
      aged 12-19 years) using snowball sampling was conducted. Content analysis was
      performed to make inferences about the focus group discussions, whereas
      statistical analyses were conducted to analyze the survey data. Results: Findings
      from the group discussions indicated that healthy eating was only an issue of
      importance when adolescents perceived negative physical changes (e.g., with
      regard to looks or physical performance). Adolescents also indicated that they
      clearly wanted to make their own food and beverage choices at school. The
      quantitative data indicated that taste, price, and variety were seen as the most
      important aspects of a healthy food assortment (mean scores 8.1, 7.8, and 7.7 on
      a 10-point scale, respectively). In general, a majority of the adolescents (64%)
      expressed that students should be involved in the organization of a healthy food
      environment in schools. At the same time, however, adolescents were not willing
      to participate themselves. This was mostly because they were skeptical about
      their ideas being heard and put into action by their schools. Conclusion: School
      based prevention programs, such as the Healthy School Program, should take into
      account that adolescents have a low risk perception of unhealthy eating and are
      seeking food choice autonomy. In addition, schools should not lose sight of
      product price, taste, and variety to make their food assortment attractive to
      students. If schools aim to involve adolescents in prevention programs that
      promote healthy eating, it is essential that they have a formal student
      involvement process that ensures that adolescents' suggestions are valued.

PMID- 29218307
TI  - Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of
      Calreticulin to the Study of Its Function.
AB  - Calreticulin is a Ca2+-binding chaperone protein, which resides mainly in the
      endoplasmic reticulum but also found in other cellular compartments including the
      plasma membrane. In addition to Ca2+, calreticulin binds and regulates almost all
      proteins and most of the mRNAs deciding their intracellular fate. The potential
      functions of calreticulin are so numerous that identification of all of them is
      becoming a nightmare. Still the recent discovery that patients affected by the
      Philadelphia-negative myeloproliferative disorders essential thrombocytemia or
      primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin
      mutations disrupting its C-terminal domain has highlighted the clinical need to
      gain a deeper understanding of the biological activity of this protein. However,
      by contrast with other proteins, such as enzymes or transcription factors, the
      biological functions of which are strictly defined by a stable spatial structure
      imprinted by their amino acid sequence, calreticulin contains intrinsically
      disordered regions, the structure of which represents a highly dynamic
      conformational ensemble characterized by constant changes between several
      metastable conformations in response to a variety of environmental cues. This
      article will illustrate the Theory of calreticulin as an intrinsically disordered
      protein and discuss the Hypothesis that the dynamic conformational changes to
      which calreticulin may be subjected by environmental cues, by promoting or
      restricting the exposure of its active sites, may affect its function under
      normal and pathological conditions.

PMID- 29218308
TI  - Opportunities for CRISPR/Cas9 Gene Editing in Retinal Regeneration Research.
AB  - While retinal degeneration and disease results in permanent damage and vision
      loss in humans, the severely damaged zebrafish retina has a high capacity to
      regenerate lost neurons and restore visual behaviors. Advancements in
      understanding the molecular and cellular basis of this regeneration response give
      hope that strategies and therapeutics may be developed to restore sight to blind
      and visually-impaired individuals. Our current understanding has been facilitated
      by the amenability of zebrafish to molecular tools, imaging techniques, and
      forward and reverse genetic approaches. Accordingly, the zebrafish research
      community has developed a diverse array of research tools for use in developing
      and adult animals, including toolkits for facilitating the generation of
      transgenic animals, systems for inducible, cell-specific transgene expression,
      and the creation of knockout alleles for nearly every protein coding gene. As
      CRISPR/Cas9 genome editing has begun to revolutionize molecular biology research,
      the zebrafish community has responded in stride by developing CRISPR/Cas9
      techniques for the zebrafish as well as incorporating CRISPR/Cas9 into available
      toolsets. The application of CRISPR/Cas9 to retinal regeneration research will
      undoubtedly bring us closer to understanding the mechanisms underlying retinal
      repair and vision restoration in the zebrafish, as well as developing therapeutic
      approaches that will restore vision to blind and visually-impaired individuals.
      This review focuses on how CRISPR/Cas9 has been integrated into zebrafish
      research toolsets and how this new tool will revolutionize the field of retinal
      regeneration research.

PMID- 29218309
TI  - Kinematic Changes during Prolonged Fast-Walking in Old and Young Adults.
AB  - Walking biomechanics is known to be influenced by speed. However, most of the
      research examining the effects of walking speed and gait characteristics has been
      conducted after a fast-walking task, neglecting the changes that may occur during
      the task. The aim of the present study was to determine the impact of fast
      walking over time on kinematics in young and old adults. Twenty-seven young
      adults (26.6 +/- 6.0 years) and 23 old adults (71.0 +/- 5.6 years) walked at 70%
      of their maximum heart rate for 20 min or until exhaustion, and the effects of
      fast-walking on temporospatial parameters and on angular kinematics were analyzed
      during the activity. During the protocol, both age-groups increased step-width
      variability. Significant effects of time were found for the ankle and hip at toe
      off for the older group. For the younger group, only the ankle angle at heel
      strike changed over time. For both groups, fast-walking induced changes in the
      coordination among the lower-limb angles that were more prominent during the
      swing phase of the gait. In conclusion, lower-limb kinematics changes in young
      adults were compatible with early signs of fatigue. The increased step-width
      variability in older adults may indicate an augmented risk of falling. Changes in
      the lower-limb walking kinematics of old adults suggest that the adjustments for
      weight acceptance and body propulsion were restricted to the hip and ankle
      joints. The kinematic changes among the lower-limb joint angles during the swing
      phase may compromise the quality of gait. These findings provide a foundation for
      future studies in the assessment of the risk of falls in older adults associated
      with walking at a faster pace.

PMID- 29218310
TI  - Non-Invasive Hemodynamic Monitoring for Hemodynamic Management in Perioperative
      Medicine.

PMID- 29218311
TI  - The Role of Relationship Type, Risk Perception, and Condom Use in Middle
      Socioeconomic Status Black Women's HIV-prevention Strategies.
AB  - This research analyzes qualitative focus group and interview data from the Sister
      Circle Study- a pilot study that explored HIV risk among middle SES Black women
      ages 25- 45 in North Carolina. Findings reveal that gendered relationship
      dynamics, perceptions of a sex ratio imbalance, and levels of trust in
      relationships may reduce some women's ability to negotiate monogamy and condom
      use with their male partners. The research suggests that higher socioeconomic
      status does not fully buffer some middle SES Black women from HIV risk and
      highlights the role interpersonal and structural factors play in shaping HIV risk
      for this group.

PMID- 29218313
TI  - Factors associated with number of duodenal samples obtained in suspected celiac
      disease.
AB  - Background and study aims:  Many people with celiac disease are undiagnosed and
      there is evidence that insufficient duodenal samples may contribute to
      underdiagnosis. The aims of this study were to investigate whether more samples
      leads to a greater likelihood of a diagnosis of celiac disease and to elucidate
      factors that influence the number of samples collected. Patients and methods:  We
      identified patients from two community hospitals who were undergoing duodenal
      biopsy for indications (as identified by International Classification of Diseases
      code) compatible with possible celiac disease. Three cohorts were evaluated: no
      celiac disease (NCD, normal villi), celiac disease (villous atrophy, Marsh score
      3), and possible celiac disease (PCD, Marsh score < 3). Endoscopic features,
      indication, setting, trainee presence, and patient demographic details were
      evaluated for their role in sample collection. Results:  5997 patients met the
      inclusion criteria. Patients with a final diagnosis of celiac disease had a
      median of 4 specimens collected. The percentage of patients diagnosed with celiac
      disease with one sample was 0.3 % compared with 12.8 % of those with six samples
      ( P  = 0.001). Patient factors that positively correlated with the number of
      samples collected were endoscopic features, demographic details, and indication (
      P  = 0.001). Endoscopist factors that positively correlated with the number of
      samples collected were absence of a trainee, pediatric gastroenterologist, and
      outpatient setting ( P  < 0.001). Conclusions:  Histological diagnosis of celiac
      disease significantly increased with six samples. Multiple factors influenced
      whether adequate biopsies were taken. Adherence to guidelines may increase the
      diagnosis rate of celiac disease.

PMID- 29218312
TI  - Potassium Homeostasis, Oxidative Stress, and Human Disease.
AB  - Potassium is the most abundant cation in the intracellular fluid and it plays a
      vital role in the maintenance of normal cell functions. Thus, potassium
      homeostasis across the cell membrane, is very critical because a tilt in this
      balance can result in different diseases that could be life threatening. Both
      Oxidative stress (OS) and potassium imbalance can cause life threatening health
      conditions. OS and abnormalities in potassium channel have been reported in
      neurodegenerative diseases. This review highlights the major factors involved in
      potassium homeostasis (dietary, hormonal, genetic, and physiologic influences),
      and discusses the major diseases and abnormalities associated with potassium
      imbalance including hypokalemia, hyperkalemia, hypertension, chronic kidney
      disease, and Gordon's syndrome, Bartter syndrome, and Gitelman syndrome.

PMID- 29218314
TI  - Endoscopic pancreatic balloon sphincteroplasty for difficult to treat pancreatic
      stones and strictures: experience in 80 patients.
AB  - Background and aim:  There is paucity of data about endoscopic pancreatic
      sphincteroplasty (EPS) after endoscopic pancreatic sphincterotomy (EPST) in the
      treatment of chronic pancreatitis. The aim of this study was to establish the
      indications for EPS, complications related to it, and to examine its
      effectiveness in managing chronic pancreatitis after a year of follow-up.
      Methods:  We evaluated the safety and efficacy of pancreatic balloon dilation
      coupled with sphincterotomy for the treatment of chronic pancreatitis. The
      technical success rate of balloon dilation, stone clearance, frequency of
      pancreatic stenting, and procedure-related adverse events were recorded. Results:
      Out of 580 patients who underwent pancreatic endotherapy between July 2014 and
      February 2016, 80 patients underwent EPS. The mean age of these 80 patients was
      34 +/- 11 years, and 80 % (n = 64) were males. The common indications were
      removal of large radiolucent stones in 31 patients; unyielding radiopaque stones
      post extracorporeal shock wave lithotripsy (ESWL) in 20 patients, and pancreatic
      duct stricture combined with stones in 29 patients. EPS could be successfully
      completed in 98.75 % of patients. Complete ductal clearance in a single session
      was achieved in only 25 patients, while 26 patients required two sessions. There
      were two adverse events of pain requiring admission for more than 24 hours and
      one procedure related bleeding, all of which were managed conservatively. The
      patients had an average follow-up of 8 months (6 - 12 months) and all the
      patients were pain free. Conclusions:  Endoscopic pancreatic sphincteroplasty is
      a relatively safe procedure with a low incidence of complications and a high rate
      of treatment success.

PMID- 29218315
TI  - A novel lens cleaner to prevent water drop adhesions during colonoscopy and
      esophagogastroduodenoscopy.
AB  - Background and study aims:  Water drop adhesions (WDA) impair endoscopic view
      during gastrointestinal endoscopy. We developed a novel lens cleaner designed
      using two types of harmLess surfactants and it is reported to be useful for
      preventing lens cloudiness during colorectal ESD. In the current study, we
      examined the ability of it for preventing and removing WDA. Patients and methods:
      During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan
      and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an
      air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The
      endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were
      calculated for various groups (lens and AWD with or without Cleash) and compared
      to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and
      30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner
      was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid
      removal were calculated, compared to those of the SL cleaner group. Results:  The
      mean WDA rate for the Cleash setting (lens: Cleash; AWD: Cleash) was 11.0 %,
      which was significantly lower than other settings (lens: SL cleaner; AWD: water,
      31.0 %; P  < 0.001) (lens: Cleash; AWD: water, 19.0 %; P  < 0.001). Clinical
      research of colonoscopies indicated that the numbers of WDA (number/15 sec) and
      WDA with non-rapid removal were 0.38 and 0.17 for the Cleash group and 0.91 and
      0.46 for the SL cleaner groups ( P  < 0.001, P  < 0.001). For
      esophagogastroduodenoscopies, the results were 0.47 and 0.24 for the Cleash group
      and 0.54 and 0.42 for the SL cleaner group ( P  = 0.72, P  = 0.018). Conclusion: 
      A clear and beautiful image without WDA is useful not only for routine endoscopy
      but also, more importantly, for magnifying endoscopy and other endoscopic
      treatments. The use of Cleash to lens and AWD showed positive results for
      preventing and removing WDA during laboratory experiments and clinical research
      involving CS. Additionally, it also showed positive results for the removal of
      WDA during EGD.

PMID- 29218316
TI  - The feasibility of colorectal endoscopic submucosal dissection for the treatment
      of residual or recurrent tumor localized in therapeutic scar tissue.
AB  - Background and study aims:  Endoscopic submucosal dissection (ESD) is used to
      treat superficial colorectal tumors. Previous studies have reported the efficacy
      of ESD for treating residual or local recurrent colorectal tumors. This study
      sought to evaluate the efficacy of ESD in treating these lesions and to assess
      factors that prevent successful ESD. Methods:  This retrospective study assessed
      25 cases of residual or local recurrent lesions that were previously treated
      using EMR (18 lesions), TEM (5 lesions), ESD (1 lesion) or surgery (1 lesion),
      and 459 primary lesions treated using ESD between April 2008 and September 2015.
      Clinicopathological characteristics, treatment outcome and adverse events were
      compared between groups with or without scar tissue. Factors related to
      perforation and a prolonged treatment time, which indicate the likelihood of
      technical difficulties, were identified using multiple logistic regression
      analysis. Results : In residual or local recurrent lesions groups, patients
      experienced more perforations (32 % vs 4 %, P  < 0.001) and required a longer
      treatment time (117 min vs 61 min, P  < 0.001) compared with the primary lesions
      group. Both groups showed a similar curative resection rate. Emergency surgery
      was not needed in any case. Multiple logistic regression analysis indicated that
      tumor location and therapeutic scar tissue were high risk factors for
      perforation, and that large tumor size and therapeutic scar tissue were high risk
      factors for prolonged treatment time. Conclusions : ESD for residual or local
      recurrent colorectal tumors is a technically challenging, but effective and
      minimally invasive treatment. When performed carefully with sufficient
      proficiency, it is a useful treatment option.

PMID- 29218317
TI  - Agreement between endoscopic ultrasound-guided fine-needle aspiration and
      endobiliary brush cytology in suspected pancreaticobiliary malignancies.
AB  - Background and study aims:  For suspected pancreaticobiliary malignancies,
      endobiliary brush cytology during endoscopic retrograde cholangiopancreatography
      (ERCP) remains the diagnostic test of choice despite historically poor and
      variable sensitivity. This has led to increased use of endoscopic ultrasound
      guided fine-needle aspiration (EUS-FNA) as an initial test. Recently, our
      institution began using a cytology brush that was designed specifically to
      collect a more substantial and higher-quality sample. The aim of this study was
      to investigate whether this brush design would provide more adequate samples and
      have high agreement with EUS-FNA in patients who underwent both procedures.
      Patients and methods:  A retrospective chart review was conducted of all patients
      who underwent both EUS-FNA and endobiliary brush cytology for suspicion of
      pancreaticobiliary malignancy from January 2013 to May 2015. A total of 41
      patients met the inclusion criteria. Initially, sample quality was evaluated.
      Final cytology results were then assessed for agreement with EUS-FNA using
      Cohen's kappa. The effect of considering atypical cytology as negative was also
      uniquely evaluated by running separate analyses. Results:  Brush cytology
      provided an adequate sample in 95.1 % of cases. Cohen's Kappa demonstrated
      moderate agreement between brush cytology and EUS-FNA: kappa = 0.42 ( P  =
      0.001). When atypical results were excluded, agreement increased: kappa = 0.60 (
      P  = 0.02), but remained moderate. If atypical results were considered
      "positive," the two procedures demonstrated equal cancer detection rates of 80.8
      %. Conclusions:  The studied brush provided more adequate samples compared with
      historical rates for brush cytology and had moderate agreement with EUS-FNA. If
      this brush truly increases sample adequacy, it could potentially provide results
      comparable to EUS-FNA at lower cost.

PMID- 29218318
TI  - Patient comfort scores do not affect endoscopist behavior during colonoscopy,
      while trainee involvement has negative effects on patient comfort.
AB  - Introduction : Patient comfort is an important part of endoscopy and reflects
      procedure quality and endoscopist technique. Using the validated, Nurse Assisted
      Patient Comfort Score (NAPCOMS), this study aimed to determine whether the
      introduction of NAPCOMS would affect sedation use by endoscopists. Patients and
      methods : The study was conducted over 3 phases. Phase One and Two consisted of 8
      weeks of endoscopist blinded and aware data collection, respectively. Data in
      Phase Three was collected over a 5-month period and scores fed back to individual
      endoscopists on a monthly basis. Results : NAPCOMS consists of 3 domains - pain,
      sedation, and global tolerability. Comparison of Phase One and Two, showed no
      significant differences in sedative use or NAPCOMS. Phase Three data showed a
      decline in fentanyl use between individual months ( P  = 0.035), but no change in
      overall NAPCOMS. Procedures involving trainees were found to use more midazolam (
      P  = 0.01) and fentanyl ( P  = 0.01), have worse NAPCOMS scores, and resulted in
      longer procedure duration ( P  < 0.001). Data comparing gastroenterologists and
      general surgeons showed increased fentanyl use ( P  = 0.037), decreased midazolam
      use ( P  = 0.001), and more position changes ( P  = 0.002) among
      gastroenterologists. Conclusions : The introduction of a patient comfort scoring
      system resulted in a decrease in fentanyl use, although with minimal clinical
      significance. Additional studies are required to determine the role of patient
      comfort scores in quality control in endoscopy. Procedures completed with
      trainees used more sedation, were longer, and had worse NAPCOMS scores, the
      implications of which, for teaching hospitals and training programs, will need to
      be further considered.

PMID- 29218319
TI  - Low yield for non-targeted biopsies of the stomach and esophagus during elective
      esophagogastroduodenoscopy.
AB  - Background and study aims:  Biopsies of non-specific mucosal findings are often
      performed during esophagogastroduodenoscopy (EGD). We sought to determine the
      prevalence and clinical utility of non-targeted biopsies of the stomach and
      esophagus. Patients and methods:  We conducted a retrospective review of 949
      outpatient EGDs performed at a US tertiary referral center. Non-targeted biopsies
      of the stomach were defined as either "normal" or "mild" to "moderate" "erythema"
      or "inflammation" without other endoscopic features. Non-targeted biopsies of the
      esophagus and gastroesophageal junction (GEJ) were defined as endoscopically
      "normal" mucosa. The primary outcome was the proportion of non-targeted biopsies
      resulting in "definite management change." Secondary outcomes included
      histopathologic diagnoses of Helicobacter pylori, intestinal metaplasia and
      esophageal eosinophilia. Results:  Of 949 EGDs, 332 (35.0 %, 95 % CI 31.9 - 38.1
      %) had a non-targeted biopsy taken at any site. Erythema in the gastric body and
      antrum was biopsied at a rate of 83 - 86 %, while biopsies of "normal"-appearing
      mucosa occurred at rates from 3 % (GEJ) to 15 % (body and antrum). The percentage
      of non-targeted biopsies that led to definite management change ranged from 5 %
      in the GEJ and esophagus to 9 % in the antrum, but did not significantly differ
      by mucosal appearance. Multivariable regression analyses suggested associations
      of language and age > 50 with management change from non-targeted gastric biopsy.
      Conclusions:  Non-targeted biopsies of the stomach and esophagus led to definite
      management change in a small proportion of patients. Further studies are needed
      to identify patient and/or endoscopic characteristics and techniques to improve
      the yield of this practice.

PMID- 29218320
TI  - Predictive relevance of lymphovascular invasion in T1 colorectal cancer before
      endoscopic treatment.
AB  - Background and aim:  The depth of tumor invasion is currently the only reliable
      predictive risk factor for lymph node metastasis before endoscopic treatment for
      colorectal cancer. However, the most important factor to predict lymph node
      metastasis has been suggested to be lymphovascular invasion rather than the depth
      of invasion. Thus, the aim of this study was to investigate the predictive
      relevance of lymphovascular invasion before endoscopic treatment. Methods:  The
      data on pT1 colorectal cancers that were resected endoscopically or surgically
      from 2007 to 2015 were retrospectively reviewed. The cases were categorized into
      two groups: positive or negative for lymphovascular invasion. The following
      factors were evaluated by univariate and multivariate analyses: age and sex of
      the patients; location, size, and morphology of the lesion; and depth of
      invasion. Results:  The positive and negative groups included 229 and 457 cases,
      respectively. Younger age ( P  < 0.01), smaller lesion size ( P  = 0.01), non-LST
      (LST: laterally spreading tumor) ( P  < 0.01), presence of depression ( P  <
      0.01), and pT1b ( P  < 0.01) were associated with lymphovascular invasion. In
      multivariate analysis, younger age (comparing patients aged <= 64 years with
      those aged > 65 years, OR, 1.81; 95 %CI, 1.29 - 2.53), presence of depression
      (OR, 1.97; CI, 1.40 - 2.77), non-LST features (OR, 1.50; CI, 1.04 - 2.15), and
      pT1b (OR, 3.08; CI, 1.91 - 4.97) were associated with lymphovascular invasion.
      Conclusion:  Younger age, presence of depression, T1b, and non-LST are associated
      with lymphovascular invasion. Therefore, careful pathological diagnosis and
      surveillance are necessary for lesions demonstrating any of these four factors.

PMID- 29218321
TI  - Visual assessment of colorectal flat and depressed lesions by using narrow band
      imaging.
AB  - Background and study aims:  Visual assessment of laterally spreading tumors non
      granular type (LST-NG) and depressed lesions by narrow band imaging (NBI) without
      magnification has not been studied. We investigated the role of non-magnifying
      NBI in detecting LST-NG and type IIc lesions on colonoscopy. Patients and
      methods:  This retrospective study examined consecutive patients diagnosed as
      having LST-NG and/or type IIc lesions in our hospital between August 2011 and
      July 2013. These lesions were classified as "Brownish area (BA)," "Brown only in
      the margins (O-ring sign)," "Same color as the normal mucosa (SC)," and "Whitish
      area (WA)" based on their appearance on non-magnifying NBI, and their appearance
      were compared with their histopathological findings. Results:  A total of 18 type
      IIc and 180 LST-NG lesions were analyzed. Among the type IIc lesions, 5 (28 %),
      12 (67 %), and 1 (5 %) were classified as BA, O-ring sign, and SC, respectively.
      Among the LST-NG lesions, 126 (70 %), 26 (14 %), and 28 lesions (16 %) were
      classified as BA, O-ring sign, and SC, respectively. The IIc lesions were found
      to have 1 lesion (20 %) with high-grade dysplasia (HGD) in the BA, and 2 lesions
      (17 %) with invasive cancer (IC) in the O-ring sign group. Among the LST-NG
      lesions, 27 (21 %) were found to have IC and 49 (39 %), HGD in the BA group; 8
      lesions (31 %) had IC and 4 (15 %) had HGD in the O-ring sign group; and 1 lesion
      (4 %) had IC and 4 (14 %) had HGD in the SC group. Conclusions:  Most flat and
      depressed colorectal lesions were seen on non-magnifying NBI as brown lesions
      with the exception of some flat lesions that were indistinguishable in color from
      the adjacent normal mucosa. Some of these flat lesions were also found to have
      HGD or IC.

PMID- 29218322
TI  - Longer observation time increases adenoma detection in the proximal colon - a
      prospective study.
AB  - Background and study aims : Longer observation times are associated with
      increased adenoma detection rates (ADR) in the entire colon. However, adenomas in
      the proximal colon are at risk of being missed during colonoscopy. The aim of
      this study was to investigate the impact of observation time on detection of
      adenomatous polyps in the proximal colon. Patients and methods : This was a
      prospective study at a university hospital in Germany. Colonoscopies were
      conducted using magnetic endoscope imaging (MEI) in order to determine the exact
      position of the scope. Exact observation times spent for the detection of polyps
      in the proximal and distal colon segments were assessed. The primary outcome was
      adenoma detection in the proximal colon. ROC curves were generated in order to
      test the correlation between observation time and adenoma detection. Logistic
      regression analysis was used to check for interfering factors. Results:  A total
      480 procedures with 538 polyps were available for analysis. The overall adenoma
      detection rate was 38.5 %. ADR in the proximal colon was 28.0 %. There was a
      significant association between observation time in the proximal colon and the
      detection of proximal adenomas ( P  < 0.001). The impact of the time factor on
      ADR was stronger in the proximal compared to the distal colon ( P  = 0.030). A
      net period of 4 min 7 sec was found to be the minimum time span for sufficient
      adenoma detection in the proximal colon. Conclusion : Observation time is
      significant in terms of adenoma detection in the proximal colon. The impact of
      observation time on ADR is stronger in the proximal compared to the distal colon.
      In the proximal colon a minimum time span of 4 minutes should be spent in order
      to ensure adequate adenoma detection.

PMID- 29218324
TI  - Intellicount: High-Throughput Quantification of Fluorescent Synaptic Protein
      Puncta by Machine Learning.
AB  - Synapse formation analyses can be performed by imaging and quantifying
      fluorescent signals of synaptic markers. Traditionally, these analyses are done
      using simple or multiple thresholding and segmentation approaches or by labor
      intensive manual analysis by a human observer. Here, we describe Intellicount, a
      high-throughput, fully-automated synapse quantification program which applies a
      novel machine learning (ML)-based image processing algorithm to systematically
      improve region of interest (ROI) identification over simple thresholding
      techniques. Through processing large datasets from both human and mouse neurons,
      we demonstrate that this approach allows image processing to proceed
      independently of carefully set thresholds, thus reducing the need for human
      intervention. As a result, this method can efficiently and accurately process
      large image datasets with minimal interaction by the experimenter, making it less
      prone to bias and less liable to human error. Furthermore, Intellicount is
      integrated into an intuitive graphical user interface (GUI) that provides a set
      of valuable features, including automated and multifunctional figure generation,
      routine statistical analyses, and the ability to run full datasets through nested
      folders, greatly expediting the data analysis process.

PMID- 29218325
TI  - Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors.
AB  - Earlier work form this laboratory showed that exposure of alveolar epithelial
      cells (AECs) to meconium caused significant cell detachment and that meconium
      induced detachment of cells was prevented by a protease inhibitor cocktail.
      Therefore, it was hypothesized that protease inhibitors might protect AEC
      monolayers against meconium-induced collapse of epithelial barrier function both
      in vitro and in vivo. To investigate this theory in vitro, albumin flux was
      measured across cultured, confluent monolayers of human type II derived cell line
      A549 on microporous filter inserts. Human meconium was collected from seven
      healthy full-term neonates and the samples were pooled and diluted prior to
      analysis. Exposure of AECs to 5% human meconium increased albumin flux across the
      cultured AEC monolayers, but the increase was significantly blocked by protease
      inhibitors (P<0.001). In C57/BL6 mice, intratracheal instillation of 5% human
      meconium increased the passage of Evans Blue Dye (EBD) from the vascular
      compartment into the alveolar spaces, measured in bronchoalveolar lavage (BAL)
      fluid after intravenous injection of EBD. Moreover, intratrachial coinstillation
      of protease inhibitors prevented the meconium-induced increase in EBD passage
      into BAL fluid (P<0.01). The data presented herein clearly demonstrate that
      protease inhibitors protect AEC barrier function against meconium-induced injury,
      and suggest the future possibility of using protease inhibitors in the treatment
      of meconium aspiration syndrome.

PMID- 29218323
TI  - SAP97 Binding Partner CRIPT Promotes Dendrite Growth In Vitro and In Vivo.
AB  - The dendritic tree is a key determinant of neuronal information processing. In
      the motor system, the dendritic tree of spinal cord neurons undergoes dramatic
      remodeling in an activity-dependent manner during early postnatal life. This
      leads to the proper segmental spinal cord connectivity that subserves normal
      locomotor behavior. One molecular system driving the establishment of dendrite
      architecture of mammalian motor neurons relies on AMPA receptors (AMPA-Rs)
      assembled with the GluA1 subunit, and this occurs in an NMDA receptor (NMDA-R)
      independent manner. The dendrite growth promoting activity of GluA1-containing
      AMPA-Rs depends on its intracellular binding partner, SAP97, and SAP97's PDZ3
      domain. We show here that cysteine-rich interactor of PDZ3 (CRIPT) is a bona fide
      SAP97 PDZ3-domain binding partner, localizes to synapses with GluA1 and SAP97
      along the dendritic tree, and is a determinant of the dendritic growth of
      mammalian spinal cord neurons. We further show that CRIPT has a well-conserved
      ortholog in the nematode, Caenorhabditis elegans, and animals lacking CRIPT
      display decreased dendrite branching of the well-studied PVD neuron in vivo. The
      lack of CRIPT leads to a selective defect in touch perception, and this is
      rescued by expression of wild-type (WT) human CRIPT (hCRIPT) in the nervous
      system. This work brings new light into the molecular machinery that drives
      dendritic growth during development and may prove relevant to the promotion of
      nervous system plasticity following insult.

PMID- 29218326
TI  - Study protocol: A multi-centre, double blind, randomised, placebo-controlled,
      parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular
      injection of anti-TNF to control disease progression in early Dupuytren's
      disease, with an embedded dose response study.
AB  - Dupuytren's disease is a common fibrotic condition of the hand affecting 4% of
      the population and causes the fingers to curl irreversibly into the palm. It has
      a strong familial tendency, there is no approved treatment for early stage
      disease, and patients with established digital contractures are most commonly
      treated by surgery. This is associated with prolonged recovery, and less invasive
      techniques have high recurrence rates.The myofibroblasts, the cells responsible
      for the excessive matrix deposition and contraction, are aggregated in nodules.
      Using excised diseased and control human tissue, we found that immune cells
      interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour
      necrosis factor (TNF) promoted the development of myofibroblasts. The clinically
      approved anti-TNF agents led to inhibition of the myofibroblast phenotype in
      vitro. This clinical trial is designed to assess the efficacy of the anti-TNF
      agent adalimumab on participants with early disease. The first part is a dose
      ranging study where nodules of participants already scheduled for surgery will be
      injected with either placebo (saline) or varying doses of adalimumab. The excised
      tissue will then be analysed for markers of myofibroblast activity.The second
      part of the study will recruit participants with early stage disease. They will
      be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals
      over 1 year and will then be followed for a further 6 months. Outcome measures
      will include nodule hardness, size and disease progression. The trial will also
      determine the cost-effectiveness of adalimumb treatment for this group of
      participants.

PMID- 29218327
TI  - Vesicle impact electrochemical cytometry compared to amperometric exocytosis
      measurements.
AB  - Three new tools are discussed for understanding chemical communication between
      cells and primarily to delve into the content and structure of nanometer
      transmitter vesicles. These are amperometric measurements of exocytosis, vesicle
      impact electrochemical cytometry, and intracellular vesicle impact
      electrochemical cytometry. These are combining in the end nanoscale mass
      spectrometry imaging to begin determination of vesicle structure. These methods
      have provided solid evidence for the concept of open and closed exocytosis
      leading to partial release of the vesicle content during normal exocytosis. They
      have also been used to discover cases where the fraction of transmitter released
      is not changed, and other cases where the vesicle transmitter fraction released
      is altered, as with zinc, thought to alter cognition. Overall, the combination of
      these methods is showing us details of vesicular processes that would not be
      measureable without these micro and nano electrochemical methods.

PMID- 29218328
TI  - Tobacco Control at Community Colleges: Context and Opportunities.
AB  - Introduction: Tobacco use among United States college-aged students remains
      higher than that of the national average. While a majority of public health
      literature has explained smoking programs and policies at traditional four-year
      colleges and universities, little research exists on programs and policies at two
      year community colleges. It is important to understand such efforts at these
      institutions as they have vastly different infrastructures and enroll a more
      diverse and at-risk student body compared to traditional four-year colleges.
      Methods: The role of community colleges in health efforts aimed at smoking was
      examined at four community colleges. Qualitative research methods included 18
      interviews and four focus groups (N=55), document review, and direct
      environmental observation. Results: Community colleges offered a limited number
      of smoking cessation and secondhand smoke prevention initiatives. All colleges
      provided cessation literature, though additional programming varied by college.
      Indoor and outdoor smoking policies existed on all campuses though enforcement
      was problematic. Little evidence was found that current program and policy
      approaches are based upon best practices or are being employed successfully.
      Conclusions: Future tobacco control initiatives at community colleges need to
      require little infrastructure and minimal staffing, and be low cost. Cessation
      tools for students must be convenient, understandable, and accessible from
      multiple locations. Feasible approaches for future initiatives could include
      testing low cost technology such as Web Assisted Tobacco Interventions (WATI) and
      outside partnerships with community organizations and health agencies. Policy
      enforcement could be improved with tobacco policy education at orientation for
      students, faculty and staff.

PMID- 29218329
TI  - High-mobility-group protein 2 regulated by microRNA-127 and small heterodimer
      partner modulates pluripotency of mouse embryonic stem cells and liver tumor
      initiating cells.
AB  - High-mobility-group protein 2 (HMGB2) expression is upregulated in human liver
      cancer. However, little is known about its regulatory function. Here we establish
      HMGB2 as a new modulator of the pluripotency of mouse embryonic stem cells
      (ESCs). Similar to OCT4 and SOX2, HMGB2 protein is highly expressed in
      undifferentiated CGR8 cells, whereas it undergoes rapid decline during embryonic
      body (EB) formation. HMGB2 interacts with OCT4, increases protein expression of
      OCT4 and SOX2, and enhances their transcriptional activities. We also show that
      miRNA-127 is a translational repressor of HMGB2 protein expression by targeting
      its 3'UTR. We further elucidate a trancrptional mechanism controlling HMGB2 mRNA
      expression by nuclear receptor SHP and transcription factor E2F1. Diminishing
      HMGB2 expression by ectopic expression of miR-127 or SHP, or treatment with a
      small molecule inhibitor inflachromene (ICM), decreases OCT4 and SOX2 expression
      and facilitates CGR8 differentiation. In addition, HMGB2 is markedly induced in
      liver tumor initiating cells (TICs). Diminishing HMGB2 expression by shHMGB2, miR
      127 or SHP impaires spheroid formation. Importantly, HMGB2 expression is elevated
      in various human cancers. Conclusion: HMGB2 acts upstream of the OCT4/SOX2
      signaling to control ESCs pluripotency. Diminishing HMGB2 expression by miR-127
      or SHP may provide a potential means to decrease the pluripotency of tumor
      initiating cells.

PMID- 29218330
TI  - Interactive effects of parental age on offspring fitness and age-assortative
      mating in a wild bird.
AB  - Variation in parental age can have important consequences for offspring fitness
      and the structure of populations and disease transmission. However, our
      understanding of the effects of parental age on offspring in natural populations
      is limited. Here, we investigate consequences of parental age for offspring
      fitness and test for age-assortative mating in a short-lived bird, the house wren
      (Troglodytes aedon). Offspring immunoresponsiveness increased with maternal age
      and decreased with paternal age, but the strength of these effects varied with
      the age of one's mate. Offspring immunoresponsiveness was augmented most with
      older mothers and younger fathers. Thus, we expected this combination of ages to
      yield the highest offspring fitness. However, offspring recruitment, longevity,
      and lifetime reproductive success were greatest when both parents were of above
      average age. Consistent with the interactive effects of parental age on offspring
      fitness, we detected positive age-assortative mating among breeding pairs. Our
      results suggest that selection favors age-assortative mating, but in different
      ways depending on how parental ages affect offspring. We suggest that, in this
      short-lived species, selection for combinations of parental ages that maximize
      offspring immune responses is likely weaker than selection to produce breeding
      adults.

PMID- 29218331
TI  - JustPoint: Identifying Colors with a Natural User Interface.
AB  - People with severe visual impairments usually have no way of identifying the
      colors of objects in their environment. While existing smartphone apps can
      recognize colors and speak them aloud, they require the user to center the object
      of interest in the camera's field of view, which is challenging for many users.
      We developed a smartphone app to address this problem that reads aloud the color
      of the object pointed to by the user's fingertip, without confusion from
      background colors. We evaluated the app with nine people who are blind,
      demonstrating the app's effectiveness and suggesting directions for improvements
      in the future.

PMID- 29218333
TI  - Secure and Efficient k-NN Queries.
AB  - Given the morass of available data, ranking and best match queries are often used
      to find records of interest. As such, k-NN queries, which give the k closest
      matches to a query point, are of particular interest, and have many applications.
      We study this problem in the context of the financial sector, wherein an
      investment portfolio database is queried for matching portfolios. Given the
      sensitivity of the information involved, our key contribution is to develop a
      secure k-NN computation protocol that can enable the computation k-NN queries in
      a distributed multi-party environment while taking domain semantics into account.
      The experimental results show that the proposed protocols are extremely
      efficient.

PMID- 29218332
TI  - Evaluating Author and User Experience for an Audio-Haptic System for Annotation
      of Physical Models.
AB  - We describe three usability studies involving a prototype system for creation and
      haptic exploration of labeled locations on 3D objects. The system uses a
      computer, webcam, and fiducial markers to associate a physical 3D object in the
      camera's view with a predefined digital map of labeled locations ("hotspots"),
      and to do real-time finger tracking, allowing a blind or visually impaired user
      to explore the object and hear individual labels spoken as each hotspot is
      touched. This paper describes: (a) a formative study with blind users exploring
      pre-annotated objects to assess system usability and accuracy; (b) a focus group
      of blind participants who used the system and, through structured and
      unstructured discussion, provided feedback on its practicality, possible
      applications, and real-world potential; and (c) a formative study in which a
      sighted adult used the system to add labels to on-screen images of objects,
      demonstrating the practicality of remote annotation of 3D models. These studies
      and related literature suggest potential for future iterations of the system to
      benefit blind and visually impaired users in educational, professional, and
      recreational contexts.

PMID- 29218334
TI  - Thiazolium salt-catalyzed C-C triple bond cleavage for accessing substituted 1
      naphthols via benzannulation.
AB  - The first thiazolium salt-catalyzed C-C triple bond cleavage of benzene-linked
      allene-ynes has been established. The reaction pathway involves [2+2]
      cycloaddition and ring-opening of in situ generated cyclobutenes with H2O under
      mild and convenient conditions, and provides practical access to substituted 1
      naphthols with potentially valuable applications.

PMID- 29218335
TI  - Chiral amine-catalyzed asymmetric conjugate addition of aldehydes to alpha
      phenylselenoenones as formal Z-allylating agents.
AB  - alpha-Selenoenones could be employed as Z-allyl precursors in the chiral amine
      catalyzed asymmetric conjugate addition of aldehydes. The obtained formal
      allylation product, a Z-olefin having a sulfonate leaving group, was employed as
      a synthetically useful chiral alkylating agent.

PMID- 29218336
TI  - Chemical signaling involved in plant-microbe interactions.
AB  - Microorganisms are found everywhere, and they are closely associated with plants.
      Because the establishment of any plant-microbe association involves chemical
      communication, understanding crosstalk processes is fundamental to defining the
      type of relationship. Although several metabolites from plants and microbes have
      been fully characterized, their roles in the chemical interplay between these
      partners are not well understood in most cases, and they require further
      investigation. In this review, we describe different plant-microbe associations
      from colonization to microbial establishment processes in plants along with
      future prospects, including agricultural benefits.

PMID- 29218337
TI  - Synthesis and photoelectrocatalytic activity of In2O3 hollow microspheres via a
      bio-template route using yeast templates.
AB  - Indium oxide (In2O3) hollow microspheres were prepared using yeast as a bio
      template with the aid of a precipitation method. The yeast provided a solid frame
      for the deposition of In(OH)3 to form the precursor. The resulting In2O3 hollow
      microspheres were obtained by calcining the precursor at 650  degrees C. The
      samples were characterized by X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption
      desorption isotherms and UV-Vis diffuse reflectance spectroscopy. The results
      showed that the diameter of the In2O3 hollow microspheres was about 2.0-3.0 MUm
      and the spherical shells were composed of In2O3 nanoparticles with a size of ~20
      nm. The BET specific surface area of the sample was 19.23 m2 g-1. The
      photoelectrocatalytic test results showed that the photoelectrocatalytic
      degradation efficiency of methylene blue (MB) using In2O3 hollow microspheres as
      catalysts under visible light irradiation and a certain voltage could reach above
      95% after 4 hours, much higher than that of only photodegradation. The enhanced
      photoelectrocatalytic activity could be attributed to the hydroxyl radicals HO
      produced by the light irradiation reaction process which could oxidize the
      electron donors and were beneficial to reducing the recombination of electrons
      and holes.

PMID- 29218338
TI  - Probing Co- and Fe-doped LaMO3 (M = Ga, Al) perovskites as thermal sensors.
AB  - The synthesis of a Co-doped or Fe-doped La(Ga,Al)O3 perovskite via the Pechini
      process aimed to achieve a color change induced by temperature and associated
      with spin crossover (SCO). In Fe-doped samples, iron was shown to be in the high
      spin state, whereas SCO from the low-spin to the high-spin configuration was
      detected in Co-doped compounds when the temperature increased. Fe-doped compounds
      clearly adopted the high-spin configuration even down to 4 K on the basis of
      Mossbauer spectroscopic analysis. The original SCO phenomenon in the Co-doped
      compounds LaGa1-xCoxO3 (0 < x < 0.1) was evidenced and discussed on the basis of
      in situ X-ray diffraction analysis and UV-vis spectroscopy. This SCO is
      progressive as a function of temperature and occurs over a broad range of
      temperatures between roughly 300  degrees C and 600  degrees C. The determination
      of a crystal field strength of about 2 eV and a Racah parameter B of about 500 cm
      1 for Co3+ (3d6) ions show that these values allow the occurrence of SCO. Hence,
      this study shows the possibility of using LaGa1-xCoxO3 compounds as thermal
      sensors at low Co contents (x = 0.02). The competition between steric and
      electronic effects in LaGaO3 in which Co3+ is stabilized in the LS state shows
      that electronic effects with the creation of M-O covalent bonds are predominant
      and contribute to the stabilization of a high crystal field around Co3+ (LS)
      although its ionic radius is smaller in comparison with that of Ga3+.

PMID- 29218339
TI  - Aerobic oxidative acylation of nitroarenes with arylacetic esters under mild
      conditions: facile access to diarylketones.
AB  - A facile and regioselective base-mediated aerobic oxidative acylation of
      nitroarenes to access diarylketones under mild conditions has been developed. It
      features the use of bench-stable and readily available arylacetates as acyl
      surrogates, and the absence of transition-metals and synthetic oxidants. This
      protocol involves a cascade CDC/oxidative decarboxylation process.

PMID- 29218340
TI  - Coexisting properties of thermostability and ultraviolet radiation resistance in
      the main S-layer complex of Deinococcus radiodurans.
AB  - Deinococcus radiodurans is well known for its unusual resistance to different
      environmental stresses. Recently, we have described a novel complex composed of
      the surface (S)-layer protein DR_2577 and the carotenoid deinoxanthin. We also
      showed a role of this complex in the UV resistance under desiccation. Both these
      properties, UV and desiccation resistance, suggest a selective pressure generated
      by Sun irradiation. In order to confirm this hypothesis we checked whether this S
      layer Deinoxanthin Binding Complex (SDBC) has features of thermo-resistance, a
      property also expected in proteins evolved under solar irradiative pressure. We
      performed the spectroscopic characterization of the SDBC by means of thermal
      shift assay, circular dichroism and related in silico analysis. Our findings
      identify a stability typical of thermo-adapted proteins and provide a new insight
      into the origin of specific S-layer types. The results are discussed in terms of
      co-evolutionary mechanisms related to Sun-induced desiccation and heat.

PMID- 29218341
TI  - Templated co-assembly into nanorods of polyanions and artificial virus capsid
      proteins.
AB  - Recombinant triblock polypeptides C-Sn-B, where C is a 400 amino acid long
      hydrophilic random coil block, Sn is a multimer of the silk-like octapeptide S =
      (GAGAGAGQ), and B = K12 is an oligolysine, have previously been shown to
      encapsulate double stranded DNA into rod-shaped, virus-like particles. In order
      to gain insight of the co-assembly process, and in order to be able to use these
      proteins for templating other types of nanorods, we here explore their co
      assembly with a range of polyanionic templates: poly(acrylic acids) (PAA) of a
      wide range of lengths, poly(styrene sulphonate) (PSS) and the stiff anionic
      polysaccharide xanthan. The formation of the complexes was characterized using
      Dynamic Light Scattering (DLS), cryogenic Transmission Electronic Microscopy
      (Cryo-TEM) and Atomic Force Microscopy (AFM). Except at very high molar masses,
      we find that flexible anionic PAA and PSS lead to co-assembly of proteins with
      single polyanion chains into nanorods, with a packing factor as expected on the
      basis of charge stochiometry. Only for very long PAA templates (8 * 105 Da) we
      find evidence for heterogeneous complexes with thin and thick sections. For the
      very stiff xanthan chains, we find that its stiffness precludes co-assembly with
      the artificial viral capsid proteins into condensed and regular nanorods. Given
      the simple and robust formation of rod-like structures with a range of
      polyanionic templates, we anticipate that the artificial virus proteins will be
      useful for preparing high-aspect ratio nanoparticles and scaffolds of precise
      size and find applications in nanotechnology and materials science for which
      currently natural rod-like viruses are being explored.

PMID- 29218342
TI  - Self-assembled N-graphene nanohollows enabling ultrahigh energy density cathode
      for Li-S batteries.
AB  - Functional porous carbon materials are widely used to solve the low conductivity
      and shuttle effect of Li-S batteries; however, the common carbon/sulfur composite
      electrodes based on traditional technology (with conducting agents and binders)
      make it difficult for a battery to work stably at an ultra-high sulfur loading of
      10 mg cm-2. Herein, an appropriate content of sulfur was injected into a
      pomegranate-like structure self-assembled with nanohollows (PSSN) of N-graphene.
      The Li-PSSN/S battery based on traditional technology displays a large-capacity,
      high-rate and long-life at an ultra-high areal-sulfur loading of 10.1 mg cm-2.
      The excellent performance with ultra-high areal-sulfur loading can be attributed
      to the hierarchal nanohollows with graphene-shells being in close contact to
      build a 3D-electronic conduction network and promoting electrolyte adsorption
      into the entire electrode to maintain rapid Li-ion transport, while stopping the
      shuttle-effect via the strong interaction of polysulfide with the doped N
      elements on graphene-shells. In addition, the exact sulfur content can provide
      just enough space to maintain the huge volume change and constant thickness of
      the S-electrodes during the charge-discharge process to enhance the cycling
      stability.

PMID- 29218343
TI  - Cyanine dyes as ratiometric fluorescence standards for the far-red spectral
      region.
AB  - Most quantitative fluorescence measurements report emission quantum yields by
      referring the integrated fluorescence profile to that of a well-known standard
      compound measured under carefully controlled conditions. This simple protocol
      works well provided an appropriate standard fluorophore is available and that the
      experimental conditions used for reference and unknown are closely comparable.
      Commercial fluorescence spectrophotometers tend to perform very well at
      wavelengths between 250 and 650 nm but are less responsive at longer wavelengths.
      There are no recognized emission standards for the far-red region. We now report
      fluorescence quantum yields for a series of commercially available cyanine dyes
      in methanol solution at room temperature. The compounds are selected to span the
      wavelength region from 600 to 850 nm, with absolute emission quantum yields being
      determined by thermal blooming spectrometry. Calibration of the instrument is
      made by reference to aluminium(iii) phthalocyanine tetrasulfonate and aza-BODIPY
      in methanol.

PMID- 29218344
TI  - Generation of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides during the
      enzymatic hydrolysis of tropical banded cricket (Gryllodes sigillatus) proteins.
AB  - Tropical banded crickets (Gryllodes sigillatus) were studied for their ability to
      yield hydrolysates with dipeptidyl peptidase IV (DPP-IV) inhibitory properties. A
      cricket protein isolate (CPI) was prepared following extraction of the water
      soluble proteins from G. sigillatus powder (CP). The extraction yield and purity
      were 20.90 +/- 0.35% and 57.0 +/- 2.23%, respectively. Endogenous proteinase
      activities were detected in the CP, which were linked to the significant protein
      breakdown seen in this sample. Fifteen CPI hydrolysates (H1-H15) were generated
      with ProtamexTM using a design of experiments (DOE) approach combining three
      parameters, temperature (40, 50 and 60  degrees C), enzyme to substrate ratio (E
      : S, 0.50, 1.25 and 2.00% (w/w)) and hydrolysis time (60, 150 and 240 min). The
      DPP-IV half maximal inhibitory concentrations (IC50) of the CPI hydrolysates
      ranged from 0.40 +/- 0.03/0.40 +/- 0.02 (H2/H3) to 1.01 +/- 0.07 mg mL-1 (H7).
      Following simulated gastrointestinal digestion (SGID), the DPP-IV IC50 of CPI
      decreased (>3.57 vs. 0.78 +/- 0.04 mg mL-1) while that of H5 increased (0.47 +/-
      0.03 vs. 0.71 +/- 0.06 mg mL-1). This study has demonstrated for the first time
      that G. sigillatus protein hydrolysates are able to inhibit DPP-IV. The study of
      these hydrolysates in vivo is needed to evaluate their potential role in
      glycaemic management.

PMID- 29218345
TI  - A coelenterazine-type bioluminescent probe for nitroreductase imaging.
AB  - Novel coelenterazine-type bioluminescent probes have been designed and
      synthesized to detect nitroreductase (NTR) in hypoxic tumors. The design strategy
      is that NTR catalyzes the reduction of the nitrobenzyl moiety to the aniline
      group with an electron donor, thus resulting in 1,4 or 1,6-rearrangement
      elimination to release coelenterazine analogues, which can be catalyzed by
      Renilla luciferase to emit bioluminescence. After careful evaluation, almost all
      probes had a 3-fold greater response for NTR over other biologically relevant
      substances at >100-fold dose more than NTR. In the dose-independent and
      selectivity study, probes A1, A2 and A5 presented a high selectivity in a dose
      dependent manner. Overall, among all molecules, probe A5 showed high sensitivity,
      low cytotoxicity and good compatibility, so as to be successfully applied for
      assessing the hypoxic status in cellulo and in vivo as the first coelenterazine
      type bioluminescent probe.

PMID- 29218346
TI  - The synthesis of a monodisperse quaternary ferrite (FeCoCrO4) from the hot
      injection thermolysis of the single source precursor
      [CrCoFeO(O2CtBu)6(HO2CtBu)3].
AB  - Monodisperse cobalt chromium ferrite (FeCoCrO4) nanoparticles have been
      synthesised using the trimetallic pivalate cluster [CrCoFeO(O2CtBu)6(HO2CtBu)3].
      The precursor was thermolysed in oleylamine and oleic acid, with diphenyl ether
      as the solvent at 260  degrees C. The effect of time and the concentration of the
      precursor on the stoichiometry of the phase formed and/or the morphology of the
      nanoparticles was studied. The reaction time was investigated by withdrawing
      aliquots at different times. No products were formed after 5 minutes and aliquots
      withdrawn at reaction times of less than 1 hour contain traces of iron oxide
      (Fe2O3); only cubic cobalt chromium ferrite (FeCoCrO4) was obtained after one
      hour. Transmission Electron Microscopy (TEM) showed that more monodisperse
      spherical ferrite nanoparticles (4.0 +/- 0.4 nm) were obtained at higher
      precursor concentrations. Magnetic measurements revealed that all the ferrite
      particles are superparamagnetic at room temperature but showed large hysteresis
      at low temperature. The nanoparticles were characterised by Powder X-Ray
      Diffraction (p-XRD) and Transmission Electron Microscopy (TEM). A Superconducting
      Quantum Interference Device (SQUID) was used to analyse the magnetic properties
      of the nanoparticles.

PMID- 29218347
TI  - Electrochemical hydrogenation of a benzannulated pyridine to a dihydropyridine in
      acidic solution.
AB  - The electrochemistry of pyridines in acidic solution is dominated by a 'weak
      acid' reduction on the cyclic voltammetry timescale. Here we show that
      electrochemical hydrogenation of a benzannulated pyridine, phenanthridine (1), to
      the biomimetic hydride donor 1,2-dihydrophenanthridine (1-H2) can occur
      selectively at glassy carbon electrodes over longer timescales of potentiostatic
      electrolysis.

PMID- 29218348
TI  - Correction: A simple model of burst nucleation.
AB  - Correction for 'A simple model of burst nucleation' by Alexandr Baronov et al.,
      Phys. Chem. Chem. Phys., 2015, 17, 20846-20852.

PMID- 29218350
TI  - Comment on "Thermal compaction of the intrinsically disordered protein tau:
      entropic, structural, and hydrophobic factors" by A. Battisti, G. Ciasca, A.
      Grottesi and A. Tenenbaum, Phys. Chem. Chem. Phys., 2017, 19, 8435.
AB  - In a recent article, A. Battisti et al., Phys. Chem. Chem. Phys., 2017, 19, 8435,
      results from SAXS measurements, metadynamic trajectories and classic MD
      trajectories at different temperatures have been used to study the temperature
      induced compaction of the intrinsically disordered protein tau. The analysis,
      though technically sound, does not provide a clear explanation of hydrophobic
      interaction strengthening on increasing the temperature and its relationship with
      the population increase of secondary structural elements. Actually, hydrophobic
      interaction is driven by the gain in translational entropy of water molecules
      associated with the decrease in solvent-excluded volume due to chain compaction.
      The magnitude of this solvent-excluded volume effect increases with temperature
      in water because the density of water is almost temperature-independent due to
      the strength of H-bonds. Since alpha-helix formation leads to a significant
      decrease in the solvent-excluded volume, the connection with hydrophobic
      interaction and chain compaction emerges directly.

PMID- 29218349
TI  - Core hydrophobicity tuning of a self-assembled particle results in efficient
      lipid reduction and favorable organ distribution.
AB  - Atherosclerosis, the deadliest disease in the United States, arises due to the
      build up of plaques in the arteries as a result of excessive cholesterol
      deposition and an impaired cholesterol removal process. High density lipoproteins
      (HDL), popularly known as "good cholesterol", are naturally occurring nano-sized
      particles that, along with apolipoproteins, are deployed to maintain cholesterol
      homeostasis in the body. Both cholesterol efflux, from the fat-laden macrophages
      in the arteries, and intracellular lipid transport, to deliver cholesterol to the
      mitochondria of liver cells for metabolism, hold key responsibilities to maintain
      healthy lipid levels inside the body. We designed a library of nine mitochondria
      targeted polymer-lipid hybrid nanoparticles (NPs), comprised of completely
      synthetic yet biodegradable components, that are capable of performing HDL-like
      functions. Using this library, we optimized a superior mitochondria targeted NP
      candidate, which can show favourable organ distribution, therapeutic potential,
      and non-toxic properties. Two targeted NP formulations with optimum NP size, zeta
      potential, and cholesterol binding and release properties were identified. Lipid
      reduction and anti-oxidative properties of these two NPs demonstrated cholesterol
      removal ability. In vivo therapeutic evaluation of the targeted-NP formulations
      in apolipoprotein E knockout (apoE-/-) mice indicated lipid reduction and anti
      inflammatory properties compared to non-targeted NPs. This synthetic targeted NP
      with potential abilities to participate in both extra- and intracellular
      cholesterol transport might potentiate therapeutic interventions for heart
      diseases.

PMID- 29218351
TI  - Synthesis and characterization of pyrrolyldipyrrin F-BODIPYs.
AB  - A series of synthetic analogs of the tripyrrolic natural product prodigiosin were
      complexed with boron trifluoride to generate the corresponding F-BODIPYs. The
      maximum wavelengths of absorption and emission of the pyrrolyldipyrrin F-BODIPYs
      were tuned through variation of the substituents about the pyrrolyldipyrrinato
      core. The limited variation of substituents on the C-ring did not significantly
      affect absorption and emission. However, variation of substituents on the B-ring
      and A-ring resulted in a corresponding red-shift in absorption and emission
      reaching maximum wavelengths of 600 nm. The presence of electron donating
      substituents on the B-ring caused a decrease in the Stokes shift, while the
      presence of electron-withdrawing substituents caused an increase, ranging from 3
      25 nm. Stokes shifts were solvent-dependant for some compounds. The inclusion of
      a dimethylamino group resulted in photo-induced electron transfer and thus
      quenched fluorescence which was restored upon protonation.

PMID- 29218352
TI  - An ultra-low frictional interface combining FDTS SAMs with molybdenum disulfide.
AB  - Interfacial friction is of crucial importance to ensure the friction-reducing and
      anti-wear properties of mechanical microstructures in micro/nanoelectromechanical
      systems (MEMS/NEMS). An ultra-low frictional interface combining hydrophobic
      1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS) self-assembled monolayers (SAMs)
      coated on an AFM tip with mechanically exfoliated molybdenum disulfide (MoS2)
      nanosheets deposited on a planar Si/SiO2 substrate was achieved. The FDTS
      SAMs/MoS2 interface between the FDTS SAMs and the MoS2 nanosheets exhibits an
      ultra-low friction force that is independent of the relative humidity. The
      incommensurate contact with ultra-low energy dissipation between FDTS and MoS2
      nanosheets and hydrophobic surface properties lead to this ultra-low frictional
      FDTS SAMs/MoS2 interface. Also, the MoS2 nanosheets have a high elastic modulus,
      which gives them a smaller contact area than the FDTS SAMs and contributes to the
      low friction. The excellent hydrophobic properties of both the FDTS SAMs and MoS2
      enable them to be unaffected by the relative humidity by preventing the capillary
      interaction. This study paves the way for extensive applications in reducing the
      friction of nanoscale contact interfaces.

PMID- 29218353
TI  - Manipulating and quantifying spin states in solution as a function of pressure
      and temperature.
AB  - Monitoring the spin states of species in solution is a crucial aspect of
      understanding magnetic properties as well as spin-labile sensing, supramolecular,
      catalytic and biochemical processes. Herein, we describe the first quantitative
      variable-pressure and variable-temperature method of determining spin states in
      solution, demonstrate that it is accurate, and identify a simultaneous T and P
      sensor system.

PMID- 29218354
TI  - 'AIE + ESIPT' assisted photorelease: fluorescent organic nanoparticles for dual
      anticancer drug delivery with real-time monitoring ability.
AB  - 'Aggregation Induced Emission + Excited State Intramolecular Proton Transfer (AIE
      + ESIPT)'-assisted photorelease of an anticancer drug by a p-hydroxyphenacyl
      (pHP) phototrigger with real-time monitoring has been demonstrated.

PMID- 29218355
TI  - The next generation vanadium flow batteries with high power density - a
      perspective.
AB  - Vanadium flow batteries (VFBs) have received increasing attention due to their
      attractive features for large-scale energy storage applications. However, the
      relatively high cost and severe polarization of VFB energy storage systems at
      high current densities restrict their utilization in practical industrial
      applications. Optimization of the performance of key VFB materials, including
      electrodes, electrolytes and membranes, can realize simultaneous minimization of
      polarization and capacity decay. The power density and energy density of VFBs are
      thus simultaneously enhanced. Moreover, relevant theoretical mechanisms and
      foundations based on virtual investigations of VFB models and simulations can
      guide these optimizations. The improved power density and energy density can
      reduce the cost of VFB energy storage systems, accelerating their successful
      industrialization. In this perspective, modification methods to optimize the
      performance of key VFB materials and investigations of models and simulations of
      VFBs will be discussed. Therefore, the available ideas and approaches will be
      provided to direct further improvements in the power density and energy density
      of VFB systems.

PMID- 29218356
TI  - Two-color vibrational imaging of glucose metabolism using stimulated Raman
      scattering.
AB  - A two-color vibrational imaging technique for simultaneously mapping glucose
      uptake and incorporation activity inside single living cells is reported.
      Heterogeneous patterns of glucose metabolism are directly visualized from the
      ratiometric two-color images for various cell types, cells undergoing epithelia
      to-mesenchymal transitions and live mouse brain tissues. The two-color imaging of
      glucose metabolism here demonstrates the development of multi-functional
      vibrational probes for multicolor imaging of cellular metabolism.

PMID- 29218358
TI  - ?

PMID- 29218357
TI  - Response to letter to the editor from Dr Rahman Shiri: The challenging topic of
      suicide across occupational groups.
AB  - We thank Dr Rahman Shiri (1) for his careful reading of our systematic review and
      meta-analysis on suicide among agricultural, forestry, and fishery workers (2).
      Our paper had the objective of providing a pooled effect size of suicide for this
      occupational group. Suicide is a crucial issue in public and occupational health.
      Suicide has a multifactorial etiology and recent systematic reviews and meta
      analyses have pointed out the role of occupational exposures, mainly psychosocial
      work stressors, as risk factors for suicide (3, 4). Suicide is a very rare event
      in the general population and still more seldom in the working population.
      Indeed, unemployed and economically inactive people have a higher risk of suicide
      compared to employed people (5, 6). However, the total number of suicides is
      greater in the employed population than among the economically inactive or
      unemployed (6). Shiri's letter (1) questioned several aspects of our review and
      meta-analysis. One comment related to the single reference database used in our
      review and a suggestion that our review could not be considered to be systematic.
      The review was based on Medline because our main interest was in quantitative
      epidemiologic studies. This is the largest database for biomedical literature and
      we would argue the most pertinent. Furthermore, we checked the reference lists of
      the most recent papers and literature reviews, and Shiri did not report any paper
      that was missing. No review, whether searching one or more databases, can expect
      to be totally exhaustive. There may always be missing studies, especially if we
      consider grey literature. Thus we assert that our review was systematic, while
      acknowledging that it may not be perfectly comprehensive. Shiri suggested an
      absence of quality assessment of the studies included in our meta-analysis.
      First, quality was considered in the context of our comments in the discussion
      section. Second, as suggested by Rothman et al (7), quality assessment was
      replaced by regression analyses of the effect of each quality item (study
      characteristics, ie, study design, effect measure, reference group, and
      adjustment). Third, because most studies included in this review were based on
      objective data (census, administrative, or register data), they were free of many
      of the sources of bias that exist in studies where information on exposure and
      outcome must be collected from participants. Consequently, many of the items
      related to quality were not pertinent, such as response and follow-up rates,
      coverage and representativeness of the sample, selection, etc. Contrary to what
      Shiri suggested, all study designs can be informative in this topic because all
      of them are able to provide an unbiased estimate of the effect size. In addition,
      the prospective and case-control studies may have shortcomings. For example, we
      excluded five studies including three prospective and case-control studies in the
      sensibility analysis because the group of interest was defined on the basis of
      the exposure to chemicals (pesticides) rather than job title. Our choice to
      retain the least adjusted models was justified because aggregated data were used
      for the meta-analysis. Therefore, unless all included studies adjusted for the
      same covariates measured in the same way, adjusted estimates cannot be
      meaningfully provided in an aggregate data meta-analysis. In addition, as the
      objective was above all descriptive and not etiological or explanatory, and as it
      is the norm in the exploration of social inequalities in health (8), the results
      from the least (gender- and age-) adjusted models were in line with the
      objective. Indeed, including more adjustment variables could lead to
      overadjustment as they may be intermediate variables on the causal pathways
      between occupation and suicide. Our strategy was in line with previous meta
      analyses on similar topics (9-11). Consequently, we would argue that our results
      are not likely to be largely due to confounding, contrary to the comment by
      Shiri. Indeed, the study of the contribution of underlying factors in explaining
      social inequalities in health outcomes is a fully-fledged topic of research (12
      15), but this is relevant research to conduct after demonstrating that
      inequalities exist between social or occupational groups. Several of Shiri's
      comments were about statistical aspects of our analyses. First, it was suggested
      that we did not correctly extract the confidence intervals for the estimates of
      several studies. We disagree. We used the STATA metan suite of commands using log
      transformed effect sizes and standard errors. Our figure 1 and the values of
      effect sizes and confidence intervals were provided by STATA, this explains why
      there may be small differences in these values compared with the results
      published in some studies. Using log-transformed effect sizes and confidence
      intervals, the analysis provided the same results. Second, our subgroup
      comparison was based on subsamples that were independent. As not all studies
      provided information for these subgroups, each subgroup was treated as a unit of
      analysis. This strategy allows the use of all relevant subgroups and comparisons
      between them (16). Third, we were also criticized for the use of random-effects
      models. Random-effects models are generally more plausible for meta-analysis
      based on studies from the published literature, because the fixed-effect model
      assumed that the entire corpus of literature has been obtained, ie, that every
      study has been or ever will be written on the topic has been included, which is
      an implausible assumption. We also assumed differences in effect size between
      studies and between subgroups, and the use of random-effects models was
      consistent with such an assumption. However, random-effects models produce wider
      confidence intervals compared to fixed-effect models (16). These models are thus
      more conservative, making our results all the more robust. One of Shiri's
      comments related to the reference group used in the studies for the comparison of
      agricultural, forestry, and fishery workers. Although we reported that the
      studies using a specific occupational group as reference group provided a higher
      effect size than the studies using other reference groups, we did not explicitly
      recognize and state in the paper that the results for Japan were based on two
      studies using a specific occupational group as reference; we concede that this
      may explain why we found a much more elevated effect size for Japan. Shiri's
      results (1) allow to conclude that the difference between Japan and the other
      geographic areas could be explained by the choice of reference group-we are
      grateful to him for raising this point. However, we would note that the effect
      size of suicide was still elevated and significant for agricultural, forestry,
      and fishery workers even after this change in the reference group for these two
      studies. Nevertheless, the choice of the optimal reference group is not obvious.
      If we consider the general population as the reference group, as unemployed
      people and economically inactive people (including people who may not be working
      due to illness or disability) are part of it and have a higher risk of suicide
      than employed people, the effect size provided by the nine studies using the
      general population as the reference is likely to be underestimated, which may
      contribute to an underestimation of the observed effect size of suicide among
      agricultural, forestry, and fishery workers in our study. The comparison was made
      in our paper with the other occupational groups (ie, the working population
      except the group of interest) as the reference, which was used by nine other
      studies, but this did not allow to determine the exact rank of the group of
      interest in the occupational hierarchy. Another relevant choice would have been
      to retain the group with the lowest suicide risk (for example, the high-skilled
      occupational group) as the reference, which would have led to a much higher
      effect size of suicide for agricultural, forestry, and fishery workers. To
      conclude, as statistical power in detecting differences between subgroups may be
      low in subgroup analyses and meta-regression, the absence of significant results
      according to subgroups found in our results cannot be interpreted as evidence
      that the effect size is the same across subgroups. Consequently, our meta
      analysis reporting a significant excess of risk of suicide among agricultural,
      forestry, and fishery workers may also be a good incentive for more research
      among this group of workers to (i) confirm this observed excess of risk using
      differing methodological approaches to meta-analysis and (ii) explore the
      potential differences within this group and the underlying factors that may
      explain this excess of risk. References 1. Shiri R. Suicide among agricultural,
      forestry, and fishery workers. Scand J Work Environ Health - online first.
      https://doi.org/10.5271/sjweh.3697 2. Klingelschmidt J, Milner A, Khireddine
      Medouni I, Witt K, Alexopoulos EC, Toivanen S, et al. Suicide among agricultural,
      forestry, and fishery workers: a systematic literature review and meta-analysis.
      Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.3682 3.
      Milner A, Witt K, LaMontagne AD, Niedhammer I. Psychosocial job stressors and
      suicidality: a meta-analysis and systematic review. Occup Environ Med - online
      first. https://doi.org/10.1136/oemed-2017-104531 4. Leach LS, Poyser C,
      Butterworth P. Workplace bullying and the association with suicidal
      ideation/thoughts and behaviour: a systematic review. Occup Environ Med.
      2017;74(1):72-9. https://doi.org/10.1136/oemed-2016-103726 5. Milner A, Page A,
      LaMontagne AD. Long-term unemployment and suicide: a systematic review and meta
      analysis. PLoS One. 2013;8(1):e51333.
      https://doi.org/10.1371/journal.pone.0051333 6. Milner A, Morrell S, Lamontagne
      AD. Economically inactive, unemployed and employed suicides in Australia by age
      and sex over a 10-year period: what was the impact of the 2007 economic
      recession? Int J Epidemiol. 2014;43(5):1500-7. https://doi.org/10.1093/ije/dyu148
      7. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology - Third Edition.
      Philadelphia: Wolters Kluwer Health - Lippincott Williams & Wilkins; 2008. 8.
      Lundberg I, Hemmingsson T, Hogstedt C. Work and social inequalities in health in
      Europe. Brussels: P.I.E. Peter Lang SA; 2007. 9. Milner A, Spittal MJ, Pirkis J,
      Lamontagne AD. Suicide by occupation: systematic review and meta-analysis. Br J
      Psychiatry. 2013;203(6):409-16. https://doi.org/10.1192/bjp.bp.113.128405 10.
      Lorant V, Deliege D, Eaton W, Robert A, Philippot P, Ansseau M. Socioeconomic
      inequalities in depression: a meta-analysis. Am J Epidemiol. 2003;157(2):98-112.
      https://doi.org/10.1093/aje/kwf182 11. Grittner U, Kuntsche S, Gmel G, Bloomfield
      K. Alcohol consumption and social inequality at the individual and country levels
      -results from an international study. Eur J Public Health. 2013;23(2):332-9.
      https://doi.org/10.1093/eurpub/cks044 12. Niedhammer I, Bourgkard E, Chau N.
      Occupational and behavioural factors in the explanation of social inequalities in
      premature and total mortality: a 12.5-year follow-up in the Lorhandicap study.
      Eur J Epidemiol. 2011;26(1):1-12. https://doi.org/10.1007/s10654-010-9506-9 13.
      Niedhammer I, Chastang JF, David S, Kelleher C. The contribution of occupational
      factors to social inequalities in health: findings from the national French SUMER
      survey. Soc Sci Med. 2008;67(11):1870-81.
      https://doi.org/10.1016/j.socscimed.2008.09.007 14. Chazelle E, Lemogne C, Morgan
      K, Kelleher CC, Chastang JF, Niedhammer I. Explanations of educational
      differences in major depression and generalised anxiety disorder in the Irish
      population. J Affect Disord. 2011;134(1-3):304-14.
      https://doi.org/10.1016/j.jad.2011.05.049 15. Niedhammer I, Lesuffleur T, Coutrot
      T, Chastang JF. Contribution of working conditions to occupational inequalities
      in depressive symptoms: results from the national French SUMER survey. Int Arch
      Occup Environ Health. 2016;89(6):1025-37.https://doi.org/10.1007/s00420-016-1142
      6 16. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta
      analysis: John Wiley & Sons, Ltd. ISBN: 978-0-470-05724-7; 2009.
      https://doi.org/10.1002/9780470743386.

PMID- 29218359
TI  - [Significance of the doctorate in scientific medical education].
AB  - According to European and German law, the medical education of physicians must
      take place in a scientific degree program at a university or under the
      supervision of a university. To keep up the ideal of a scientific degree program,
      various organizations and associations, such as the German Research Foundation,
      the German Council of Science and Humanities and the German Medical Faculty
      Association, see the need for an even stronger anchoring of academic learning
      content in the course of study. Traditionally, a scientific project, which is
      carried out during the studies, provides the basis for the Doctor of Medicine
      (Dr. med.) after graduation, although the research projects as a basis for
      medical degrees are currently not obligatory parts of the curricula. The number
      of medical students performing such research projects is significantly
      decreasing, thus they are missing major skills for working in science. To
      counteract these developments, faculties of medicine are currently developing
      model curricula including deepened scientific education. Despite these efforts,
      the German Association of Faculties of Medicine argues that the performance of
      research projects leading to the doctoral degree is most suitable for obtaining
      expertise in scientific work. According to recommendations by the German Council
      of Science on the requirements for quality assurance of graduation doctoral
      degree programs have been introduced. This and further measures, like MD/PhD
      programs or research-based additional study programs serving the scientific
      qualification of medical students, are the subject of this article.

PMID- 29218360
TI  - Bioengineered Cardiac Tissue Based on Human Stem Cells for Clinical Application.
AB  - Engineered cardiac tissue might enable novel therapeutic strategies for the human
      heart in a number of acquired and congenital diseases. With recent advances in
      stem cell technologies, namely the availability of pluripotent stem cells, the
      generation of potentially autologous tissue grafts has become a realistic option.
      Nevertheless, a number of limitations still have to be addressed before clinical
      application of engineered cardiac tissue based on human stem cells can be
      realized. We summarize current progress and pending challenges regarding the
      optimal cell source, cardiomyogenic lineage specification, purification, safety
      of genetic cell engineering, and genomic stability. Cardiac cells should be
      combined with clinical grade scaffold materials for generation of functional
      myocardial tissue in vitro. Scale-up to clinically relevant dimensions is
      mandatory, and tissue vascularization is most probably required both for
      preclinical in vivo testing in suitable large animal models and for clinical
      application. Graphical Abstract.

PMID- 29218362
TI  - Further Experience with Oral Paracetamol as a Rescue Therapy for Patent Ductus
      Arteriosus in Preterm Infants.

PMID- 29218363
TI  - Chest computed tomography angiography in children on extracorporeal membrane
      oxygenation (ECMO).
AB  - Performing chest CT angiography on pediatric patients on extracorporeal membrane
      oxygenation (ECMO) can be challenging. Successfully performing CT angiography in
      these children requires substantial communication and coordination between the
      radiologists and clinical care providers. Additionally, the radiologist must
      understand the child's anatomy and disease pathophysiology, flow dynamics of the
      ECMO circuit, image acquisition timing, contrast injection site, and volume, rate
      and duration of contrast administration. In this article we highlight the vital
      factors the radiologist needs to consider to optimize the chest CT angiography in
      pediatric patients on ECMO.

PMID- 29218364
TI  - Ultrasound evaluation of stress injuries and physiological adaptations in the
      fingers of adolescent competitive rock climbers.
AB  - BACKGROUND: The impact of high-intensity, repetitive training on the fingers of
      adolescent climbers is relatively unknown. OBJECTIVE: To evaluate this effect by
      ultrasound (US) and to confirm some findings by magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: The US study was performed in 20 adolescent rock climbers
      (ages 10-17 years) and 6 non-climbing controls (ages 11-15 years). US was used to
      examine the third digit of the right hand for differences in thickness of soft
      tissue, flexor and extensor tendon, volar plate and bony and growth plate
      adaptations. In four climbers with finger deformity or pain, 3-T MR images were
      compared with US findings. Number of hours/week and years of climbing were used
      to group climbers in three levels (3=most intense training). Mann-Whitney test
      was used for statistical analysis. RESULTS: Compared with non-climbing controls,
      climbers demonstrated significantly thicker flexor tendons, volar plates and soft
      tissues. Joint effusions were found in 13/19 (68%) climbers. Significant
      phalangeal malalignment was seen in 10/19 (53%) climbers. Growth plate
      deformities were identified in three level 3 climbers. US findings correlated
      with MRI for effusions, phalangeal growth plate injury, malalignment and adaptive
      changes. MRI additional showed capsule rupture (n=1), stress fracture (n=1) and
      phalangeal physeal stress injury (n=1). CONCLUSION: Competitive rock climbing
      results in physiological adaptations in the fingers, an example being significant
      soft-tissue hypertrophy of the flexor. US demonstrated several non-physiological
      changes in response to repetitive stress in half of the climbers. MRI showed
      additional stress injuries to the growth plate, joints and bone.

PMID- 29218365
TI  - Pediatric Radiology Editorial Board - acknowledgments and updates.

PMID- 29218367
TI  - Cirrhosis and LI-RADS.
AB  - Chronic liver disease, irrespective of cause, can eventually lead to cirrhosis,
      which is the primary risk factor for developing hepatocellular carcinoma (HCC).
      In patients with cirrhosis or appropriate risk factors, HCC can be diagnosed by
      imaging with high specificity using liver imaging reporting and data system
      v2017, obviating the need for histologic confirmation. Confident recognition of
      cirrhosis by conventional imaging alone can be challenging, as radiologists are
      not always provided with the requisite information to determine if the patient
      has cirrhosis or other risk factors for HCC. Moreover, cirrhosis-associated
      abnormalities may impair the diagnostic accuracy of imaging for HCC. This article
      addresses the diagnosis of cirrhosis by non-invasive imaging and the implications
      of cirrhosis for imaging interpretation and accuracy.

PMID- 29218366
TI  - Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma
      patients with low levels of immune-suppressor cells.
AB  - We report a novel phase 2 clinical trial in patients with poor prognosis
      refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical
      donor natural killer (NK) cell therapy (NK dose 0.5-3.27 * 107 NK cells/kg) with
      rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated
      without graft-versus-host disease, cytokine release syndrome, or neurotoxicity.
      Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2
      months: 2 had complete response lasting 3 and 9 months. Circulating donor NK
      cells persisted for at least 7 days after infusion at the level 0.6-16 donor NK
      cells/ul or 0.35-90% of total CD56 cells. Responding patients had lower levels of
      circulating host-derived Tregs (17 +/- 4 vs. 307 +/- 152 cells/uL; p = 0.008) and
      myeloid-derived suppressor cells at baseline (6.6 +/- 1.4% vs. 13.0 +/- 2.7%; p =
      0.06) than non-responding patients. Lower circulating Tregs correlated with low
      serum levels of IL-10 (R 2 = 0.64; p < 0.003; n = 11), suggestive of less
      immunosuppressive milieu. Low expression of PD-1 on recipient T cells before
      therapy was associated with response. Endogenous IL-15 levels were higher in
      responders than non-responding patients at the day of NK cell infusion (mean +/-
      SEM: 30 +/- 4; n = 4 vs. 19.0 +/- 4.0 pg/ml; n = 8; p = 0.02) and correlated with
      day 14 NK cytotoxicity as measured by expression of CD107a (R 2 = 0.74; p =
      0.0009; n = 12). In summary, our observations support development of donor NK
      cellular therapies for advanced NHL as a strategy to overcome chemoresistance.
      Therapeutic efficacy may be further improved through disruption of the
      immunosuppressive environment and infusion of exogenous IL-15.

PMID- 29218368
TI  - Are there four tibial plateau columns? Yes there are, as illustrated by a postero
      lateral apple-bite fracture. Response to a letter-to-the-editor.

PMID- 29218369
TI  - Peripheral nerve ultrasound findings in mucolipidosis type 3.
AB  - PURPOSE: The mucolipidoses are rare autosomal recessive lysosomal storage
      disorders. Neurologic involvement in these conditions is generally thought to be
      limited to cognitive delay and entrapment neuropathies (primarily carpal tunnel
      syndrome). We sought to evaluate peripheral nerves in this condition using nerve
      ultrasound. METHODS: We performed peripheral nerve ultrasound in two siblings
      with genetically confirmed mucolipidosis type 3 (alpha/beta). RESULTS: Peripheral
      nerves in mucolipidosis type 3 (alpha/beta) exhibit multifocal enlargement.
      CONCLUSION: The peripheral nerve ultrasound has a role in the evaluation of this,
      and possibly other lysosomal storage disorders.

PMID- 29218371
TI  - Highlights from the 40th ESNR Annual Meeting, the 24th Advanced Course in
      Diagnostic Neuroradiology and the 9th Advanced Course in Interventional
      Neuroradiology-Malmo 2017.

PMID- 29218370
TI  - Differentiation of residual/recurrent gliomas from postradiation necrosis with
      arterial spin labeling and diffusion tensor magnetic resonance imaging-derived
      metrics.
AB  - PURPOSE: The aim of this study is to differentiate recurrent/residual gliomas
      from postradiation changes using arterial spin labeling (ASL) perfusion and
      diffusion tensor imaging (DTI)-derived metrics. METHODS: Prospective study was
      conducted upon 42 patients with high-grade gliomas after radiotherapy only or
      prior to other therapies that underwent routine MR imaging, ASL, and DTI. The
      tumor blood flow (TBF), fractional anisotropy (FA), and mean diffusivity (MD) of
      the enhanced lesion and related edema were calculated. The lesion was categorized
      as recurrence/residual or postradiation changes. RESULTS: There was significant
      differences between residual/recurrent gliomas and postradiation changes of TBF
      (P = 0.001), FA (P = 0.001 and 0.04), and MD (P = 0.001) of enhanced lesion and
      related edema respectively. The area under the curve (AUC) of TBF of enhanced
      lesion and related edema used to differentiate residual/recurrent gliomas from
      postradiation changes were 0.95 and 0.93 and of MD were 0.95 and 0.81 and of FA
      were 0.81 and 0.695, respectively. Combined ASL and DTI metrics of the enhanced
      lesion revealed AUC of 0.98, accuracy of 95%, sensitivity of 93.8%, specificity
      of 95.8%, positive predictive value (PPV) of 93.8%, and negative predictive value
      (NPV) of 95.8%. Combined metrics of ASL and DTI of related edema revealed AUC of
      0.97, accuracy of 92.5%, sensitivity of 93.8%, specificity of 91.7%, PPV of
      88.2%, and NPV of 95.7. CONCLUSION: Combined ASL and DTI metrics of enhanced
      lesion and related edema are valuable noninvasive tools in differentiating
      residual/recurrent gliomas from postradiation changes.

PMID- 29218372
TI  - Location, Root Proximity, and Glyphosate-Use History Modulate the Effects of
      Glyphosate on Fungal Community Networks of Wheat.
AB  - Glyphosate is the most-used herbicide worldwide and an essential tool for weed
      control in no-till cropping systems. However, concerns have been raised regarding
      the long-term effects of glyphosate on soil microbial communities. We examined
      the impact of repeated glyphosate application on bulk and rhizosphere soil fungal
      communities of wheat grown in four soils representative of the dryland wheat
      production region of Eastern Washington, USA. Further, using soils from paired
      fields, we contrasted the response of fungal communities that had a long history
      of glyphosate exposure and those that had no known exposure. Soil fungal
      communities were characterized after three cycles of wheat growth in the
      greenhouse followed by termination with glyphosate or manual clipping of plants.
      We found that cropping system, location, year, and root proximity were the
      primary drivers of fungal community compositions, and that glyphosate had only
      small impacts on fungal community composition or diversity. However, the taxa
      that responded to glyphosate applications differed between rhizosphere and bulk
      soil and between cropping systems. Further, a greater number of fungal OTUs
      responded to glyphosate in soils with a long history of glyphosate use. Finally,
      fungal co-occurrence patterns, but not co-occurrence network characteristics,
      differed substantially between glyphosate-treated and non-treated communities.
      Results suggest that most fungi influenced by glyphosate are saprophytes that
      likely feed on dying roots.

PMID- 29218373
TI  - Correction to: Geosmithia-Ophiostoma: a New Fungus-Fungus Association.
AB  - The article Geosmithia-Ophiostoma: a New Fungus-Fungus Association, written by
      Alessia L. Pepori, Priscilla P. Bettini, Cecilia Comparini, Sabrina Sarrocco,
      Anna Bonini, Arcangela Frascella, Luisa Ghelardini, & Aniello Scala, Giovanni
      Vannacci, Alberto Santini.

PMID- 29218374
TI  - The effect of vitamin U on the lung tissue of pentyleneterazole-induced seizures
      in rats.
AB  - The aim of this study is to investigate the therapeutic effects of vitamin U (Vit
      U) on lung tissue of pentyleneterazole (PTZ)-induced seizures in rats. Sprague
      Dawley male rats were randomly divided into four groups as follows: control (0.9%
      NaCl given, intraperitoneally); Vit U (50 mg/kg/day, for 7 days by gavage); PTZ;
      (60 mg/kg one dose, intraperitoneally); and PTZ + Vit U (in same dose and time).
      At the end of the experiment, lung tissues were taken and examined biochemically
      and cytologically. Lipid peroxidation (LPO), glutathione (GSH), sialic acid (SA),
      and nitric oxide (NO) levels, and superoxide dismutase (SOD) and catalase (CAT)
      activities were determined in lung homogenates. Imprinted lung samples were
      stained with May Grunwald-Giemsa stain and microscopically examined for the
      presence of collagen fibers, macrophage, leucocyte, and epithelial cells. PTZ
      administration significantly increased GSH level and CAT activity and
      significantly decreased SOD activity compared to the control group. Vit U
      administration significantly increased GSH level and CAT activity compared to the
      control group. GSH and NO levels significantly decreased in PTZ + Vit U group
      compared to the PTZ group. In cytologic analysis, increased collagen fibers,
      macrophages, leucocytes, and epithelial cells were observed in PTZ group compared
      to the control group, and Vit U administration decreased these cytological
      parameters compared to the PTZ group. The findings of this study support the
      possible protective role of using Vit U as an add-on therapy in order to prevent
      lung tissue injury which may occur during seizures in epilepsy.

PMID- 29218375
TI  - Genetic analysis of multi-environmental spring wheat trials identifies genomic
      regions for locus-specific trade-offs for grain weight and grain number.
AB  - KEY MESSAGE: GWAS on multi-environment data identified genomic regions associated
      with trade-offs for grain weight and grain number. Grain yield (GY) can be
      dissected into its components thousand grain weight (TGW) and grain number (GN),
      but little has been achieved in assessing the trade-off between them in spring
      wheat. In the present study, the Wheat Association Mapping Initiative (WAMI)
      panel of 287 elite spring bread wheat lines was phenotyped for GY, GN, and TGW in
      ten environments across different wheat growing regions in Mexico, South Asia,
      and North Africa. The panel genotyped with the 90 K Illumina Infinitum SNP array
      resulted in 26,814 SNPs for genome-wide association study (GWAS). Statistical
      analysis of the multi-environmental data for GY, GN, and TGW observed
      repeatability estimates of 0.76, 0.62, and 0.95, respectively. GWAS on BLUPs of
      combined environment analysis identified 38 loci associated with the traits.
      Among them four loci-6A (85 cM), 5A (98 cM), 3B (99 cM), and 2B (96 cM)-were
      associated with multiple traits. The study identified two loci that showed
      positive association between GY and TGW, with allelic substitution effects of 4%
      (GY) and 1.7% (TGW) for 6A locus and 0.2% (GY) and 7.2% (TGW) for 2B locus. The
      locus in chromosome 6A (79-85 cM) harbored a gene TaGW2-6A. We also identified
      that a combination of markers associated with GY, TGW, and GN together explained
      higher variation for GY (32%), than the markers associated with GY alone (27%).
      The marker-trait associations from the present study can be used for marker
      assisted selection (MAS) and to discover the underlying genes for these traits in
      spring wheat.

PMID- 29218376
TI  - Genetic dissection and validation of candidate genes for flag leaf size in rice
      (Oryza sativa L.).
AB  - KEY MESSAGE: Two major loci with functional candidate genes were identified and
      validated affecting flag leaf size, which offer desirable genes to improve leaf
      architecture and photosynthetic capacity in rice. Leaf size is a major
      determinant of plant architecture and yield potential in crops. However, the
      genetic and molecular mechanisms regulating leaf size remain largely elusive. In
      this study, quantitative trait loci (QTLs) for flag leaf length and flag leaf
      width in rice were detected with high-density single nucleotide polymorphism
      genotyping of a chromosomal segment substitution line (CSSL) population, in which
      each line carries one or a few chromosomal segments from the japonica cultivar
      Nipponbare in a common background of the indica variety Zhenshan 97. In total, 14
      QTLs for flag leaf length and nine QTLs for flag leaf width were identified in
      the CSSL population. Among them, qFW4-2 for flag leaf width was mapped to a 37-kb
      interval, with the most likely candidate gene being the previously characterized
      NAL1. Another major QTL for both flag leaf width and length was delimited by
      substitution mapping to a small region of 13.5 kb that contains a single gene,
      Ghd7.1. Mutants of Ghd7.1 generated using CRISPR/CAS9 approach showed reduced
      leaf size. Allelic variation analyses also validated Ghd7.1 as a functional
      candidate gene for leaf size, photosynthetic capacity and other yield-related
      traits. These results provide useful genetic information for the improvement of
      leaf size and yield in rice breeding programs.

PMID- 29218377
TI  - Genetic mapping of a major gene in triticale conferring resistance to bacterial
      leaf streak.
AB  - KEY MESSAGE: A major gene conferring resistance to bacterial leaf streak was
      mapped to chromosome 5R in triticale. Bacterial leaf streak (BLS), caused by
      Xanthomonas translucens pv. undulosa (Xtu), is an important disease of wheat and
      triticale around the world. Although resistance to BLS is limited in wheat,
      several triticale accessions have high levels of resistance. To characterize the
      genetic basis of this resistance, we developed triticale mapping populations
      using a resistant accession (Siskiyou) and two susceptible accessions (UC38 and
      Villax St. Jose). Bulked segregant analysis in an F2 population derived from the
      cross of Siskiyou * UC38 led to the identification of a simple sequence repeat
      (SSR) marker (XSCM138) on chromosome 5R that co-segregated with the resistance
      gene. The cross of Siskiyou * Villax St. Jose was advanced into an F2:5
      recombinant inbred line population and evaluated for BLS reaction. Genetic
      linkage maps on this population were assembled with markers generated using
      genotyping-by-sequencing as well as several SSR markers previously identified on
      5R. Quantitative trait locus (QTL) mapping revealed a single major QTL on
      chromosome 5R, underlined by the same SSR marker as in the Siskiyou * UC38
      population. The F1 hybrids of the two crosses were highly resistant to BLS,
      indicating that resistance is largely dominant. This work will facilitate
      introgression of this rye-derived BLS resistance gene into the wheat genome by
      molecular marker-mediated chromosome engineering.

PMID- 29218378
TI  - Efficiency of multi-trait, indirect, and trait-assisted genomic selection for
      improvement of biomass sorghum.
AB  - KEY MESSAGE: We compare genomic selection methods that use correlated traits to
      help predict biomass yield in sorghum, and find that trait-assisted genomic
      selection performs best. Genomic selection (GS) is usually performed on a single
      trait, but correlated traits can also help predict a focal trait through indirect
      or multi-trait GS. In this study, we use a pre-breeding population of biomass
      sorghum to compare strategies that use correlated traits to improve prediction of
      biomass yield, the focal trait. Correlated traits include moisture, plant height
      measured at monthly intervals between planting and harvest, and the area under
      the growth progress curve. In addition to single- and multi-trait direct and
      indirect GS, we test a new strategy called trait-assisted GS, in which correlated
      traits are used along with marker data in the validation population to predict a
      focal trait. Single-trait GS for biomass yield had a prediction accuracy of 0.40.
      Indirect GS performed best using area under the growth progress curve to predict
      biomass yield, with a prediction accuracy of 0.37, and did not differ from
      indirect multi-trait GS that also used moisture information. Multi-trait GS and
      single-trait GS yielded similar results, indicating that correlated traits did
      not improve prediction of biomass yield in a standard GS scenario. However, trait
      assisted GS increased prediction accuracy by up to [Formula: see text] when using
      plant height in both the training and validation populations to help predict
      yield in the validation population. Coincidence between selected genotypes in
      phenotypic and genomic selection was also highest in trait-assisted GS. Overall,
      these results suggest that trait-assisted GS can be an efficient strategy when
      correlated traits are obtained earlier or more inexpensively than a focal trait.

PMID- 29218380
TI  - Mountain ultra-marathon finishers exhibit marked immune alterations similar to
      those of severe trauma patients.

PMID- 29218381
TI  - Effectiveness of a two-step population-based osteoporosis screening program using
      FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE)
      study.
AB  - : The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated
      the effectiveness of a two-step screening program for osteoporosis in women. We
      found no overall reduction in fractures from systematic screening compared to the
      current case-finding strategy. The group of moderate- to high-risk women, who
      accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION:
      The purpose of the ROSE study was to investigate the effectiveness of a two-step
      population-based osteoporosis screening program using the Fracture Risk
      Assessment Tool (FRAX) derived from a self-administered questionnaire to select
      women for DXA scan. After the scanning, standard osteoporosis management
      according to Danish national guidelines was followed. METHODS: Participants were
      randomized to either screening or control group, and randomization was stratified
      according to age and area of residence. Inclusion took place from February 2010
      to November 2011. Participants received a self-administered questionnaire, and
      women in the screening group with a FRAX score >= 15% (major osteoporotic
      fractures) were invited to a DXA scan. Primary outcome was incident clinical
      fractures. Intention-to-treat analysis and two per-protocol analyses were
      performed. RESULTS: A total of 3416 fractures were observed during a median
      follow-up of 5 years. No significant differences were found in the intention-to
      treat analyses with 34,229 women included aged 65-80 years. The per-protocol
      analyses showed a risk reduction in the group that underwent DXA scanning
      compared to women in the control group with a FRAX >= 15%, in regard to major
      osteoporotic fractures, hip fractures, and all fractures. The risk reduction was
      most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). CONCLUSIONS:
      Compared to an office-based case-finding strategy, the two-step systematic
      screening strategy had no overall effect on fracture incidence. The two-step
      strategy seemed, however, to be beneficial in the group of women who were
      identified by FRAX as moderate- or high-risk patients and complied with DXA.

PMID- 29218383
TI  - Linburg-Comstock variation and syndrome. A meta-analysis.
AB  - INTRODUCTION: Linburg-Comstock variation often connecting the flexor pollicis
      longus and flexor digitorum profundus of the index finger at a different level
      with significant discrepancy between clinical and cadaveric frequencies reported
      in the literature. Although this variation is quite prevalent, it is yet
      frequently unrecognized. The aim of this meta-analysis is to generate more
      accurate weighted frequency values of the Linburg-Comstock variation and to look
      for possible association with ethnicity, laterality, gender and side. METHODS: A
      systematic literature search identified 14 studies, including 4132
      forearms/hands, which met the inclusion criteria. RESULTS: While no significant
      difference was found for laterality, we found significantly higher Linburg
      Comstock variation rate in females compared to males. Turkish population
      demonstrated a significantly higher crude frequency when compared to Europeans
      (22.2 vs. 15.2%). Hispanic population showed the highest crude frequency (34.5%),
      whereas the African ancestry showed the least one (8.8%). CONCLUSIONS: Linburg
      Comstock variation could cause career-threatening disabilities and could
      complicate some hand injuries as well. This review invites future researchers to
      use a single nomenclature; the term "Linburg-Comstock variation" is to be used
      when no symptoms are present, and the term "Linburg-Comstock syndrome" in cases
      where the variation is symptomatic.

PMID- 29218382
TI  - Restrictive pulmonary dysfunction is associated with vertebral fractures and bone
      loss in elderly postmenopausal women.
AB  - : Association between lung function and bone metabolism remains controversial. We
      found that impaired lung function was associated with vertebral fractures and
      bone loss in Japanese postmenopausal women. While vertebral deformities would
      impair lung function, respiratory dysfunction might in turn increase fracture
      risk, suggesting a complex bidirectional interaction. INTRODUCTION: Association
      between bone metabolism and pulmonary function in the general population is
      controversial. The aim of this study was to investigate relationship between lung
      and bone parameters in elderly postmenopausal women. METHODS: One hundred and six
      postmenopausal women (75.6 +/- 8.0 years old) who underwent spirometric tests
      were examined for prevalent vertebral fractures, bone mineral density (BMD), bone
      metabolic markers, and other metabolic indices such as urinary pentosidine.
      RESULTS: Multivariable logistic regression analyses revealed that forced vital
      capacity (FVC) (OR = 0.063, 95% CI: 0.011-0.352, p = 0.002) and urinary
      pentosidine (OR = 1.067, 95% CI: 1.020-1.117, p = 0.005) were associated with the
      presence of vertebral fractures after adjustment for height loss, age, and BMD at
      femoral neck. Moreover, vital capacity (VC) or FVC as well as body mass index and
      age was among independent determinants of BMD after adjustment for height loss
      and the number and grade of vertebral fractures in forced multiple linear
      regression analysis (VC: beta = 0.212, p = 0.021, FVC: beta = 0.217, p = 0.031).
      Urinary pentosidine was negatively correlated with pulmonary function parameters
      such as FVC and forced expiratory volume in 1 s (FEV1.0), although these
      correlations appeared dependent on age. CONCLUSIONS: Diminished FVC was
      associated with prevalent vertebral fractures and decreased BMD in Japanese
      postmenopausal women without apparent pulmonary diseases. Mechanism of such
      association between pulmonary function and bone status remains to be determined.

PMID- 29218385
TI  - Bilateral carotid-anterior cerebral artery anastomoses associated with bilateral
      ophthalmic arteries arising from the anastomotic arteries diagnosed by magnetic
      resonance angiography: a case report.
AB  - Rarely, the anterior cerebral artery (ACA) arises from the ophthalmic segment of
      the internal carotid artery, a condition described as carotid-ACA anastomosis or
      infraoptic course of the ACA that generally demonstrates right-sided
      predominance. We diagnosed a case of bilateral anastomoses of the carotid and ACA
      vessels in which bilateral ophthalmic arteries arose from the origins of the
      anastomotic vessels using magnetic resonance (MR) angiography. Identification of
      rare arterial variations on MR angiography requires careful scrutiny of source
      images, and creation of partial volume-rendering images can aid visualization of
      detailed anatomic structures.

PMID- 29218384
TI  - Is it possible to give a single definition of the rectosigmoid junction?
AB  - AIM: The rectosigmoid junction is the limit separating the sigmoid colon and
      rectum. This transition zone has different definitions. We want to highlight
      different landmarks of the rectosigmoid junction (RSJ), to help the clinicians to
      adopt a consensual definition. METHOD: We reviewed anatomical, endoscopic,
      physiological and surgical points of view concerning the rectosigmoid junction
      (RSJ). RESULTS: The rectosigmoid junction has a different definition depending on
      who is studying it. Nevertheless, it is a high pressure location, a place
      connecting different muscles organizations, neurological systems or vascular
      anastomosis. The clear pathophysiology of the RSJ is not yet determined with
      certainty, but its resection is essential for the therapeutic care of patients
      and also for the improvement of surgical skills. From a surgical point of view,
      anatomical landmarks has to be chosen: easily reproducible and identifiable. The
      disappearance of taenia coli (belonging to the colon) and the peritoneal
      reflection (recto-genital pouch), located below the upper rectum, seem the most
      reliable. The level of rectal section must, in any case, be below the promontory.
      CONCLUSION: There is not a single definition, but rather several definitions of
      the RSJ. Each one of them reflects one appearance of this region: embryological
      and anatomical evolution or clinical entity. From a surgical point of view, the
      criterion which seems to be the most reliable is the disappearance of taenia coli
      and the peritoneal reflection (recto-genital pouch).

PMID- 29218386
TI  - Anatomical study of medial sural artery and its perforators in Nepalese: an aid
      to reconstructive surgery.
AB  - OBJECTIVE: The present study was undertaken to know the anatomical basis of
      medial sural artery (MSA) and its perforators in Nepalese. METHODS: The popliteal
      arteries of 16 preserved cadaveric lower limbs were injected with a mixture of
      red ink and glycerine. The number, location, diameter of perforators; length and
      intramuscular course of pedicle; the branching pattern of MSA were observed and
      measured. RESULTS: The mean of 2.2 +/- 1.2 perforators (range 0-4) was observed.
      The perforators were clustered between 8.6 and 25.7 cm from the popliteal crease
      and 0.3-7.5 cm from posterior midline of leg. The dominant perforators were
      observed in middle 1/3rd of the leg. The average pedicle length was 12.04 +/-
      3.27 cm. The intramuscular courses of pedicles were observed in deep and
      superficial strata in 65.7 and 34.3%, respectively. The MSA originated from
      popliteal artery in 62.5% and common sural artery in 37.5%. An accessory MSA was
      found in 12.5%. Type I and Type III branching patterns of MSA were observed in
      31.2% each whereas Type II was found in 37.5%. The mean external diameter of
      perforators and MSA were 0.85 +/- 0.27 mm and 2.2 +/- 0.43 mm, respectively.
      CONCLUSIONS: The metrical presentation of this study provides an easy access to
      know about the distribution of perforators and branching pattern of MSA which
      will help the surgeons to make a convenient plan to harvest the MSA perforator
      flap in Nepalese population.

PMID- 29218379
TI  - A prospective international observational prevalence study on prone positioning
      of ARDS patients: the APRONET (ARDS Prone Position Network) study.
AB  - INTRODUCTION: While prone positioning (PP) has been shown to improve patient
      survival in moderate to severe acute respiratory distress syndrome (ARDS)
      patients, the rate of application of PP in clinical practice still appears low.
      AIM: This study aimed to determine the prevalence of use of PP in ARDS patients
      (primary endpoint), the physiological effects of PP, and the reasons for not
      using it (secondary endpoints). METHODS: The APRONET study was a prospective
      international 1-day prevalence study performed four times in April, July, and
      October 2016 and January 2017. On each study day, investigators in each ICU had
      to screen every patient. For patients with ARDS, use of PP, gas exchange,
      ventilator settings and plateau pressure (Pplat) were recorded before and at the
      end of the PP session. Complications of PP and reasons for not using PP were also
      documented. Values are presented as median (1st-3rd quartiles). RESULTS: Over the
      study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of
      the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS
      patients had at least one session of PP (13.7%), with no differences among the 4
      study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9%
      (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The
      duration of the first PP session was 18 (16-23) hours. Measured with the patient
      in the supine position before and at the end of the first PP session, PaO2/FIO2
      increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure
      decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased
      from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not
      using PP (64.3%) was that hypoxemia was not considered sufficiently severe.
      Complications were reported in 12 patients (11.9%) in whom PP was used (pressure
      sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two,
      and a transient increase in intracranial pressure in one). CONCLUSIONS: In
      conclusion, this prospective international prevalence study found that PP was
      used in 32.9% of patients with severe ARDS, and was associated with low
      complication rates, significant increase in oxygenation and a significant
      decrease in driving pressure.

PMID- 29218387
TI  - Anatomic parameters of the sacral lamina for osteosynthesis in transverse sacral
      fractures.
AB  - PURPOSE: To analyze the morphometric parameters of the dorsal sacral lamina and
      pedicles to determine if there is adequate bony architecture to support plate
      osteosynthesis. METHODS: Two reviewers performed measurements on 98 randomly
      selected high-resolution CT scans of the pelvis to quantify the bony anatomy of
      the sacral lamina. Measurements included the depths of the lamina at each sacral
      level, the trajectory and depth of the sacral pedicles from the sacral lamina,
      and the width of the sacral canal. A bone mineral density analysis was performed
      on the sacral lamina using Hounsfield units (HU) and compared to the L1 and S1
      vertebral bodies. RESULTS: The sacral lamina were found to form peaks and troughs
      which we refered to as major and minor sections. On average, the thickness was >
      4 mm at all major screw starting points, indicating adequate geometry for screw
      fixation. The sacral pedicle depths were 27, 18, 16, and 14 mm at S2-S5,
      respectively. The average angulation from midline of this screw path directed
      laterally to avoid the sacral canal was 20 degrees , 17 degrees , 8 degrees , and
      - 8 degrees  for the S2-5 pedicles, respectively. Average sacral canal diameter
      was 11 mm for S2 and 8 mm for S3-5. The sacral lamina had an average bone mineral
      density of 635 HU, which was significantly different from the density of the L5
      (220 HU) and S1 (165 HU) vertebral bodies (p < 0.005). This morphometric data was
      used to pilot a new plating technique. CONCLUSIONS: The sacral lamina offers a
      novel target for screw fixation and meets the basic geometric and compositional
      criteria for screw purchase. To our knowledge, this study represents the first
      morphometric analysis performed on the sacral lamina and pedicles for plate
      application.

PMID- 29218388
TI  - Correlation of sociodemographic and clinical parameters with depression and
      distress in patients with hematologic malignancies.
AB  - A quarter of cancer patients struggle with distress or depression during their
      illness. Multiple organizations including the National Comprehensive Cancer
      Network recommend universal screening for distress and depression. Herein, we
      describe a universal screening program in patients with hematologic malignancies
      and factors associated with distress and depression. Between December 2013 and
      February 2015, patients with hematologic malignancies took the Patient Health
      Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their
      first outpatient parenteral chemotherapy. Patient demographic information as well
      as information regarding visit burden and baseline use of psychiatric medications
      were recorded. A PHQ-9 score of >= 9 and a DT score >= 4 suggested a high risk of
      major depression and distress. Intergroup comparisons of categorical and
      continuous variables were performed via chi-square and Wilcoxon rank-sum tests.
      Multivariate models were constructed using the stepwise selection technique using
      all potential variables. Two hundred forty-six patients with a median age at
      diagnosis 65 years (range 18-94 years) were included. In the multivariate
      analysis, a PHQ-9 score >= 9 was associated with living alone (P = 0.007),
      positive PHQ-2 (P = 0.003), and high Charlson comorbidity index (CCI; P = 0.02),
      while a DT score >= 4 was associated with being married (P = 0.03) and female (P
      = 0.03). There was no other association with high scores on either questionnaire.
      Patients with hematologic malignancies often have prolonged treatment and
      surveillance. We identified subpopulations within this group who may be at high
      risk of developing distress and depression and who should be aggressively
      screened even when universal screening programs are not available.

PMID- 29218390
TI  - Gemelli-obturator complex in the deep gluteal space: an anatomic and dynamic
      study.
AB  - OBJECTIVE: To investigate the behavior of the sciatic nerve during hip rotation
      at subgluteal space. MATERIALS AND METHODS: Sonographic examination (high
      resolution ultrasound machine at 5.0-14 MHZ) of the gemelli-obturator internus
      complex following two approaches: (1) a study on cadavers and (2) a study on
      healthy volunteers. The cadavers were examined in pronation, pelvis-fixed
      position by forcing internal and external rotations of the hip with the knee in
      90 degrees  flexion. Healthy volunteers were examined during passive internal and
      external hip rotation (prone position; lumbar and pelvic regions fixed). Subjects
      with a history of major trauma, surgery or pathologies affecting the examined
      regions were excluded. RESULTS: The analysis included eight hemipelvis from six
      fresh cadavers and 31 healthy volunteers. The anatomical study revealed the
      presence of connective tissue attaching the sciatic nerve to the structures of
      the gemellus-obturator system at deep subgluteal space. The amplitude of the
      nerve curvature during rotating position was significantly greater than during
      resting position. During passive internal rotation, the sciatic nerve of both
      cadavers and healthy volunteers transformed from a straight structure to a curved
      structure tethered at two points as the tendon of the obturator internus
      contracted downwards. Conversely, external hip rotation caused the nerve to
      relax. CONCLUSION: Anatomically, the sciatic nerve is closely related to the
      gemelli-obturator internus complex. This relationship results in a reproducible
      dynamic behavior of the sciatic nerve during passive hip rotation, which may
      contribute to explain the pathological mechanisms of the obturator internal
      gemellus syndrome.

PMID- 29218391
TI  - CT-guided percutaneous biopsy of sclerotic bone lesions: diagnostic outcomes.
AB  - OBJECTIVE: To determine the diagnostic yield of CT-guided percutaneous biopsy of
      densely sclerotic bone lesions. MATERIALS AND METHODS: We retrospectively
      analyzed CT-guided percutaneous bone biopsies performed at our institution from
      September 2008 through August 2011 (329 cases) and from September 2012 through
      August 2015 (324 cases) after adoption of a battery-powered drill system
      (OnControl). Bone lesions were included in the analysis if they were >70%
      sclerotic by visual inspection, had a density > 2 times that of adjacent
      trabecular bone, and had an attenuation of >=250 HU. Pathological fractures,
      diskitis-osteomyelitis, and osteoid osteomas were excluded. Eligible cases were
      characterized by lesion location, maximum lesion diameter, mean density, biopsy
      needle type and gauge, reported complications, and histological diagnosis.
      Clinical and imaging follow-up was used to confirm histological diagnosis. Cases
      in which a benign histological diagnosis could not be confirmed by imaging over a
      minimum period of 1 year were excluded. RESULTS: A total of 37 biopsies of
      sclerotic bone lesions met the inclusion criteria, 17 of which were performed
      with a power drill needle and 20 of which were performed with a manually driven
      needle. The mean lesion density was 604.1 HU. The overall diagnostic yield was
      78.4%; overall diagnostic accuracy was 94.6%, and the false-negative rate was
      5.4%. Diagnostic yield and accuracy were 82.4% and 100% respectively, with a
      power drill and 75% and 90% respectively, with a manual device. Diagnostic yield
      for lesions >=700 HU was 90% (9 out of 10). CONCLUSION: Densely sclerotic bone
      lesions are amenable to percutaneous needle biopsy.

PMID- 29218392
TI  - Unusual circumstances to diagnose cervical Pott's disease.
AB  - Tuberculous spondylodiscitis usually affects the dorso-lumbar spine, and its
      cervical location is a rare condition that can mimic other diseases and
      consequently cause treatment delays. We report a case of tuberculous
      spondylodiscitis of the lower cervical spine discovered under unusual
      circumstances in a patient with severe polytrauma involving a cranio-cerebral
      trauma, a non-displaced fracture of the two laminae and the spinous process of
      the C6 vertebrae as well as fibular and tibial shaft fractures. The patient
      underwent static tibial nailing, and a collar with occipital and chin supports
      was applied. At 2-month follow-up, the patient presented with severe neck pain
      without neurologic deficits. Plain and dynamic cervical radiographs showed a
      stable C6-C7 subluxation and C7 superior endplate collapse. The CT scan also
      outlined prevertebral soft tissue swelling. The MRI showed a C6-C7
      spondylodiscitis associated with a prevertebral abscess with am 8-cm major axis.
      The diagnosis of C6-C7 Pott's disease was confirmed by a CT-guided biopsy. The
      patient received 12 months of antituberculous chemotherapy, after which the
      paravertebral abscess completely disappeared, and the patient has had no
      functional sequelae. The diagnosis of cervical spine tuberculosis is difficult
      and requires a high level of attention. Delays in establishing the diagnosis and
      starting the appropriate treatment result in severe complications such as spinal
      cord compression and spinal deformity, which are difficult to manage.

PMID- 29218389
TI  - Primary prophylaxis of invasive fungal infections in patients with haematological
      malignancies: 2017 update of the recommendations of the Infectious Diseases
      Working Party (AGIHO) of the German Society for Haematology and Medical Oncology
      (DGHO).
AB  - Immunocompromised patients are at high risk of invasive fungal infections (IFI),
      in particular those with haematological malignancies undergoing remission
      induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic
      syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants
      (HSCT). Despite the development of new treatment options in the past decades, IFI
      remains a concern due to substantial morbidity and mortality in these patient
      populations. In addition, the increasing use of new immune modulating drugs in
      cancer therapy has opened an entirely new spectrum of at risk periods. Since the
      last edition of antifungal prophylaxis recommendations of the German Society for
      Haematology and Medical Oncology in 2014, seven clinical trials regarding
      antifungal prophylaxis in patients with haematological malignancies have been
      published, comprising 1227 patients. This update assesses the impact of this
      additional evidence and effective revisions. Our key recommendations are the
      following: prophylaxis should be performed with posaconazole delayed release
      tablets during remission induction chemotherapy for AML and MDS (AI).
      Posaconazole iv can be used when the oral route is contraindicated or not
      feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI
      rates in acute lymphoblastic leukaemia (ALL) patients during induction
      chemotherapy, and there is poor evidence to recommend it for prophylaxis in these
      patients (CI). Despite substantial risk of IFI, we cannot provide a stronger
      recommendation for these patients. There is poor evidence regarding voriconazole
      prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM
      should be performed within 2 to 5 days of initiating voriconazole prophylaxis and
      should be repeated in case of suspicious adverse events or of dose changes of
      interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not
      recommended (CIItu), but may be helpful in cases of clinical failure such as
      breakthrough IFI for verification of compliance or absorption.

PMID- 29218393
TI  - "Microperc" micropercutaneous nephrolithotomy: a review of the literature.
AB  - Recent years have seen innovations in working armamentarium of percutaneous
      nephrolithotomy (PCNL) leading to development of novel modifications such as
      miniperc, ultra miniperc, and microperc. Amongst these microperc appears to be
      least invasive and various authors, off late, have reported their experience with
      the technique. Literature on microperc was reviewed by a MEDLINE/PubMed search
      with articles in the English language since 2011 in published peer-reviewed
      journals. Articles comprised of case series, comparative, and noncomparative
      studies. Different facets encompassing the technique were analyzed including
      contemporary indications, technique and its modifications, outcomes, and
      comparison with other modalities. Technique is reported to be associated with
      high success rate (82-100%) and short hospital stay (1-2 days). Studies have
      reported minimal hemoglobin drop (0.1-1.4 gm%) and fewer complications of lower
      Clavien grades. Going small in PCNL has gone a long way to present day 4.85F
      puncture system. Utilization of this novel modification is on rise with larger
      case series and comparative analysis being reported in past 2 years. Technique
      boasts of high clearance rate, lower morbidity and short hospital stay. In the
      present era, this innovation in percutaneous stone management appears to be
      another milestone in quest for "knife to cannula to needle to nothing".

PMID- 29218394
TI  - Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and
      memory impairments in the valproic acid rat model of autism.
AB  - RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive
      neurodevelopmental disorders that manifest in early childhood, and it is growing
      up to be a major cause of disability in children. However, the etiology and
      treatment of ASD are not well understood. In our previous study, we found that
      serum levels of sphingosine 1-phosphate (S1P) were increased significantly in
      children with autism, indicating that S1P levels may be involved in ASD.
      OBJECTIVE: The objective of this study was to identify a link between increased
      levels of S1P and neurobehavioral changes in autism. METHODS: We utilized a
      valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P
      and the expression of sphingosine kinase (SphK), a key enzyme for S1P production,
      in serum and hippocampal tissue. Furthermore, we assessed cognitive functional
      changes and histopathological and neurochemical alterations in VPA-exposed rats
      after SphK blockade to explore the possible link between increased levels of S1P
      and neurobehavioral changes in autism. RESULTS: We found that SphK2 and S1P are
      upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological
      inhibition of SphK reduced S1P levels, attenuated spatial learning and memory
      impairments, increased the expression of phosphorylated CaMKII and CREB and
      autophagy-related proteins, inhibited cytochrome c release, decreased the
      expression of apoptosis related proteins, and protected against neuronal loss in
      the hippocampus. CONCLUSION: We have demonstrated that an increased level of
      SphK2/S1P is involved in the spatial learning and memory impairments of autism,
      and this signaling pathway represents a novel therapeutic target and direction
      for future studies.

PMID- 29218395
TI  - Inferring phylogenetic trees from the knowledge of rare evolutionary events.
AB  - Rare events have played an increasing role in molecular phylogenetics as
      potentially homoplasy-poor characters. In this contribution we analyze the
      phylogenetic information content from a combinatorial point of view by
      considering the binary relation on the set of taxa defined by the existence of a
      single event separating two taxa. We show that the graph-representation of this
      relation must be a tree. Moreover, we characterize completely the relationship
      between the tree of such relations and the underlying phylogenetic tree. With
      directed operations such as tandem-duplication-random-loss events in mind we
      demonstrate how non-symmetric information constrains the position of the root in
      the partially reconstructed phylogeny.

PMID- 29218396
TI  - [Multiple well demarcated skin erosions and ulcers following exanthematous drug
      eruption after sultamicillin therapy].
AB  - This article presents the case of a patient with newly developed skin erosions
      and ulcerations following an exanthematous drug eruption due to sultamicillin
      therapy. The skin lesions were treated topically with clobetasol and
      prednicarbate and orally with methylprednisolone. A skin smear revealed massive
      growth of Escherichia coli bacteria. Blood cultures were negative. The cause for
      developing ecthyma gangrenosum in our patient were iatrogenic immunosuppression
      and transient bacteremia.

PMID- 29218398
TI  - Enhanced hemoglobin-oxygen unloading in migratory salmonids.
AB  - Recent findings indicate that some teleost fishes may be able to greatly enhance
      hemoglobin-oxygen (Hb-O2) unloading at the tissues under conditions that result
      in catecholamine release. The putative mechanism relies on the high pH
      sensitivity of teleost hemoglobin (Hb), intracellular red blood cell (RBC) pH
      regulation via beta-adrenergic Na+/H+ exchanger (beta-NHE) activity, and plasma
      accessible carbonic anhydrase at the tissues that short-circuits RBC pH
      regulation. Previous studies have shown that in rainbow trout, this system may
      double Hb-O2 unloading to red muscle compared to a situation without short
      circuiting. The present study determined that: (1) in rainbow trout this system
      may be functional even at low concentrations of circulating catecholamines, as
      shown by conducting a dose-response analysis; (2) Atlantic and coho salmon also
      possess beta-NHE activity, as shown by changes in hematocrit in adrenergically
      stimulated cells; and (3) with beta-NHE short-circuiting, Atlantic and coho
      salmon may be able to increase Hb-O2 unloading by up to 74 and 159%,
      respectively, as determined by modeling based on O2 equilibrium curves. Together,
      these results indicate that a system to enhance Hb-O2 unloading may be common
      among salmonids and may be operational even under routine conditions. In view of
      the life histories of Atlantic and coho salmon, a system to enhance Hb-O2
      unloading during exercise may help determine a successful spawning migration and
      thus reproductive success.

PMID- 29218399
TI  - Lung Image: Doege-Potter Syndrome.

PMID- 29218397
TI  - Can we better predict the biologic behavior of incidental IPMN? A comprehensive
      analysis of molecular diagnostics and biomarkers in intraductal papillary
      mucinous neoplasms of the pancreas.
AB  - PURPOSE: Predicting the biologic behavior of intraductal papillary mucinous
      neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms
      and imaging characteristics to determine appropriate surgical candidates.
      However, the majority of resected cysts remain low-risk lesions, many of which
      may be feasible to have under surveillance. We herein characterize the most
      promising and up-to-date molecular diagnostics in order to identify optimal
      components of a molecular signature to distinguish levels of IPMN dysplasia.
      METHODS: A comprehensive systematic review of pertinent literature, including our
      own experience, was conducted based on the PRISMA guidelines. RESULTS: Molecular
      diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and
      serum were evaluated and organized into the following categories: oncogenes,
      tumor suppressor genes, glycoproteins, markers of the immune response,
      proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific
      targets in each of these categories, and in aggregate, were identified by their
      ability to both characterize a cyst as an IPMN and determine the level of cyst
      dysplasia. CONCLUSIONS: Combining molecular signatures with clinical and imaging
      features in this era of next-generation sequencing and advanced computational
      analysis will enable enhanced sensitivity and specificity of current models to
      predict the biologic behavior of IPMN.

PMID- 29218400
TI  - [Emotional robots in a nursing context : Empirical analysis of the present use
      and the effects of Paro and Pleo].
AB  - BACKGROUND: It has been questioned by researchers in robotics as well in the
      general public to what extent companion-type robots can support the elderly with
      the fulfillment of their psychological and social needs. Although these robots
      have already been used in care settings in Germany, research has referred little
      to this practical experience in order to analyze their impact and benefit. To
      start to close this gap, the current article reports on the current use of
      companion-type robots in care settings, on the effects reported by professional
      caregivers as well as on the role of psychosocial needs in the acceptance and use
      of companion-type robots by the elderly. MATERIAL AND METHODS: In the first
      study, 30 professional caregivers with experience in the use of the robot seal
      Paro in care settings were interviewed regarding Paro's application and the
      observed effects on their clients. In the second study, three case examples are
      presented from an interaction study in which vulnerable elderly persons had the
      robot dinosaur Pleo at their disposal for a maximum period of 15 days. RESULTS:
      Paro is used very flexibly in a variety of settings and with a broad range of
      user groups (study 1). The reported psychosocial effects were mainly positive but
      short term. The case examples (study 2) show that psychosocial needs can both
      foster or hinder robot acceptance and use. They also emphasize the important role
      of caregivers in the interaction between the elderly and emotional robots in the
      context of eldercare. CONCLUSION: The beneficial and ethical use of companion
      type robots in care settings demands a high commitment on the part of the
      caregivers. Given this prerequisite, emotional robots can be a valuable
      therapeutic tool.

PMID- 29218401
TI  - Using multimedia information and communication technology (ICT) to provide added
      value to reminiscence therapy for people with dementia : Lessons learned from
      three field studies.
AB  - BACKGROUND: In the care of people with dementia (PwD), occupational therapies and
      activities aiming at maintaining the quality of life of PwD, such as reminiscence
      therapy (RT), are taking on a more and more important role. Information and
      communication technology (ICT) has the potential to improve and to facilitate RT
      by facilitating access to and selection of biographical information and related
      contents or by providing novel multimodal interaction forms to trigger memories;
      however, interactive multimedia technology is barely used in practice.
      OBJECTIVES, MATERIALS AND METHODS: This article presents three exploratory field
      studies that evaluated different aspects of RT technology use for PwD in care
      homes, including the utilization of online movie databases, interactive surface
      touch computers as well as natural user interfaces allowing gestures and haptic
      interaction. In these studies, the usage of prototype systems was observed in
      occupational sessions by 5, 12 and 16 PwD. RESULTS AND CONCLUSION: The results
      indicate positive effects of technology use, e. g. in the form of verbally
      elicited reminiscence statements, expressed joy and playful interaction. Lessons
      learned for the design of technology-based RT interventions are presented and
      discussed.

PMID- 29218402
TI  - Linking inter-individual variability to endocrine disruptors: insights for
      epigenetic inheritance.
AB  - Endocrine disrupting chemicals (EDCs) can induce a myriad of adverse health
      effects. An area of active investigation is the multi- and transgenerational
      inheritance of EDC-induced adverse health effects referring to the transmission
      of phenotypes across multiple generations via the germline. The inheritance of
      EDC-induced adverse health effects across multiple generations can occur
      independent of genetics, spurring much research into the transmission of
      underlying epigenetic mechanisms. Epigenetic mechanisms play important roles in
      the development of an organism and are responsive to environmental exposures. To
      date, rodent studies have demonstrated that acquired epigenetic marks,
      particularly DNA methylation, that are inherited following parental EDC exposure
      can escape embryonic epigenome reprogramming. The acquired epimutations can lead
      to subsequent adult-onset diseases. Increasing studies have reported inter
      individual variations that occur with epigenetic inheritance. Factors that
      underlie differences among individuals could reveal previously unidentified
      mechanisms of epigenetic transmission. In this review, we give an overview of DNA
      methylation and posttranslational histone modification as the potential
      mechanisms for disease transmission, and define the requirements for multi- and
      transgenerational epigenetic inheritance. We subsequently evaluate rodent studies
      investigating how acquired changes in epigenetic marks especially DNA methylation
      across multiple generations can vary among individuals following parental EDC
      exposure. We also discuss potential sources of inter-individual variations and
      the challenges in identifying these variations. We conclude our review discussing
      the challenges in applying rodent generational studies to humans.

PMID- 29218404
TI  - The stone surgeon in the mirror: how are German-speaking urologists treating
      large renal stones today?
AB  - OBJECTIVE: To elucidate the current treatment strategies of LRS in German
      speaking Europe. Little is known about the treatment of large renal stones (LRS >
      3 cm) in daily urological practice. LRS therapy can be, however, challenging and
      hazardous. MATERIALS AND METHODS: A 39 item web-based survey was performed among
      urologists listed by the German, Austrian and Swiss Associations of Urology,
      addressing professionals treating LRS "on their own" and working in a German
      speaking country. Uniparametric descriptions indicated as absolute numbers and
      percentages without p values, simple linear associations and bubble plots without
      arithmetic means or bar charts with standard deviation between targeted
      parameters and percentages were used. RESULTS: 266 of the 6586 responding
      urologists claimed to treat urinary stones on a regular basis. The majority of
      them were male (90.2%) and over 50 years old (42.9%). Most stones are treated in
      non-university hospitals (69.5%). 81.9% of all the institutions treat more than
      150 cases/y. Open surgery is still performed in 45.5% of the centres, laparoscopy
      in 32%. Percutaneous nephrolithotomy (PNL) is the primary treatment option.
      Antimicrobial strategies vary considerably. Serious complications seem to be
      rare. However, quite a few responders reported treatment-related deaths. The main
      limitation is the absolute number of urologists performing LRS treatment, which
      is unknown. CONCLUSIONS: The German-speaking urologist treating LRS is a male and
      over 50. Although he performs PNL primarily, he is not averse to open surgery and
      SWL. He applies guidelines and employs modern equipment. Only antimicrobial
      strategies are out of line with the international standards.

PMID- 29218405
TI  - Multimodal treatments combined with gamma knife surgery for primary atypical
      teratoid/rhabdoid tumor of the central nervous system: a single-institute
      experience of 18 patients.
AB  - OBJECTIVES: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly malignant
      tumor of the central nervous system with poor prognosis. Nowadays, multimodal
      management, including surgery, chemotherapy (CMT), and radiation therapy (RT), is
      advocated. However, AT/RT treatment with gamma knife surgery (GKS) was rarely
      reported. The aim of this study was to assess the efficacy and safety of GKS for
      the treatment of AT/RT. PATIENTS AND METHODS: Medical records of AT/RT patients
      who underwent surgery from 2007 to 2014 at the West China Hospital were
      retrospectively reviewed and statistically analyzed. RESULTS: Eighteen patients
      (12 males and 6 females) were presented with AT/RTs. Median age during
      presentation was 20.5 months (range, 4-179 months). Twelve patients were < 3
      years and six patients were > 3 years. Tumor location was supratentorial in seven
      patients, infratentorial in ten patients, and center area of the brain in one
      patient. Treatments performed were as follows: surgery alone in two patients,
      surgery+RT in two patients, surgery+CMT in five patients, surgery+CMT+RT in two
      patients, and surgery+CMT+RT+GKS in seven patients. The 2-year overall survival
      (OS) rate and event-free survival (EFS) rate for all 18 consecutive patients were
      33.3 and 27.8%, respectively. Cox regression analyses showed that multimodal
      management combined with GKS was an independent positive prognostic factor for
      OS. CONCLUSIONS: Although AT/RTs are lethal cancer types, the OS of the disease
      was improved by using multimodal therapeutic strategies, including surgery, CMT,
      and RT, combined with GKS.

PMID- 29218403
TI  - The storage and recall of memories in the hippocampo-cortical system.
AB  - A quantitative computational theory of the operation of the hippocampus as an
      episodic memory system is described. The CA3 system operates as a single
      attractor or autoassociation network (1) to enable rapid one-trial associations
      between any spatial location (place in rodents or spatial view in primates) and
      an object or reward and (2) to provide for completion of the whole memory during
      recall from any part. The theory is extended to associations between time and
      object or reward to implement temporal order memory, which is also important in
      episodic memory. The dentate gyrus performs pattern separation by competitive
      learning to create sparse representations producing, for example, neurons with
      place-like fields from entorhinal cortex grid cells. The dentate granule cells
      generate, by the very small number of mossy fibre connections to CA3, a
      randomizing pattern separation effect that is important during learning but not
      recall and that separates out the patterns represented by CA3 firing as being
      very different from each other. This is optimal for an unstructured episodic
      memory system in which each memory must be kept distinct from other memories. The
      direct perforant path input to CA3 is quantitatively appropriate for providing
      the cue for recall in CA3 but not for learning. The CA1 recodes information from
      CA3 to set up associatively learned backprojections to the neocortex to allow the
      subsequent retrieval of information to the neocortex, giving a quantitative
      account of the large number of hippocampo-neocortical and neocortical-neocortical
      backprojections. Tests of the theory including hippocampal subregion analyses and
      hippocampal NMDA receptor knockouts are described and support the theory.

PMID- 29218406
TI  - Correction to: Acute and chronic neuromuscular adaptations to local vibration
      training.
AB  - The author would like to correct the reference in the publication of the original
      article. The corrected reference is given below for your reading.

PMID- 29218407
TI  - Short vs. long pulses for testing knee extensor neuromuscular properties: does it
      matter?
AB  - PURPOSE: The present study aimed at comparing knee extensor neuromuscular
      properties determined with transcutaneous electrical stimulation using two pulse
      durations before and after a standardized fatigue protocol. METHODS: In the first
      sub-study, 19 healthy participants (ten women and nine men; 28 +/- 5 years) took
      part to two separate testing sessions involving the characterization of voluntary
      activation (twitch interpolation technique), muscle contractility (evoked forces
      by single and paired stimuli), and neuromuscular propagation (M-wave amplitude
      from vastus lateralis and vastus medialis muscles) obtained at supramaximal
      intensity with a pulse duration of either 0.2 or 1 ms. The procedures were
      identical in the second sub-study (N = 11), except that neuromuscular properties
      were also evaluated after a standardized fatiguing exercise. Electrical
      stimulation was delivered through large surface electrodes positioned over the
      quadriceps muscle and a visual analog scale was used to evaluate the discomfort
      to paired stimuli evoked at rest. RESULTS: There was no difference between pulse
      durations in the estimates of voluntary activation, neuromuscular propagation,
      and muscle contractility both in the non-fatigued and fatigued states. The
      discomfort associated with supramaximal paired electrical stimuli was also
      comparable between the two pulse durations. CONCLUSIONS: It appears that 0.2- and
      1-ms-long pulses provide a comparable evaluation of knee extensor neuromuscular
      properties.

PMID- 29218408
TI  - Transcription profiling and identification of infection-related genes in
      Phytophthora cactorum.
AB  - Phytophthora cactorum, an oomycete pathogen, infects more than 200 plant species
      within several plant families. To gain insight into the repertoire of the
      infection-related genes of P. cactorum, Illumina RNA-Seq was used to perform a
      global transcriptome analysis of three life cycle stages of the pathogen, mycelia
      (MY), zoospores (ZO) and germinating cysts with germ tubes (GC). From over 9.8
      million Illumina reads for each library, 18,402, 18,569 and 19,443 distinct genes
      were identified for MY, ZO and GC libraries, respectively. Furthermore, the
      transcriptome difference among MY, ZO and GC stages was investigated. Gene
      ontology (GO) and KEGG pathway enrichment analyses revealed diverse biological
      functions and processes. Comparative analysis identified a large number of genes
      that are associated with specific stages and pathogenicity, including 166
      effector genes. Of them, most of RXLR and NLP genes showed induction while the
      majority of CRN genes were down-regulated in GC, the important pre-infection
      stage, compared to either MY or ZO. And 14 genes encoding small cysteine-rich
      (SCR) secretory proteins showed differential expression during the developmental
      stages and in planta. Ectopic expression in the Solanaceae indicated that SCR113
      and one elicitin PcINF1 can trigger cell death on Nicotiana benthamiana, tobacco
      (N. tabacum) and tomato (Solanum lycopersicum) leaves. Neither conserved domain
      nor homologues of SCR113 in other organisms can be identified. Collectively, our
      study provides a comprehensive examination of gene expression across three P.
      cactorum developmental stages and describes pathogenicity-related genes, all of
      which will help elucidate the pathogenicity mechanism of this destructive
      pathogen.

PMID- 29218409
TI  - In focus in HCB.

PMID- 29218411
TI  - Effect of clinical information and previous exam execution on observer agreement
      and reliability in the analysis of hysteroscopic video-recordings.
AB  - INTRODUCTION: Inter-observer agreement and reliability in hysteroscopic image
      assessment remain uncertain and the type of factors that may influence it has
      only been studied in relation to the experience of hysteroscopists. We aim to
      assess the effect of clinical information and previous exam execution on observer
      agreement and reliability in the analysis of hysteroscopic video-recordings.
      MATERIALS AND METHODS: Ninety hysteroscopies were video-recorded and randomized
      into a group without (Group 1) and with clinical information (Group 2). The
      videos were independently analyzed by three hysteroscopists, regarding lesion
      location, dimension, and type, as well as decision to perform a biopsy. One of
      the hysteroscopists had executed all the exams before. Proportions of agreement
      (PA) and kappa statistics (kappa) with 95% confidence intervals (95% CI) were
      used. RESULTS: In Group 2, there was a higher proportion of a normal diagnosis (p
      < 0.001) and a lower proportion of biopsies recommended (p = 0.027). Observer
      agreement and reliability were better in Group 2, with the PA and kappa ranging,
      respectively, from 0.73 (95% CI 0.62, 0.83) and 0.44 (95% CI 0.26, 0.63), for
      image quality, to 0.94 (95% CI 0.88, 0.99) and 0.85 (95% CI 0.65, 0.95), for the
      decision to perform a biopsy. Execution of the exams before the analysis of the
      video-recordings did not significantly affect the results. CONCLUSION: With
      clinical information, agreement and reliability in the overall analysis of
      hysteroscopic video-recordings may reach almost perfect results and this was not
      significantly affected by the execution of the exams before the analysis.
      However, there is still uncertainty in the analysis of specific endometrial
      cavity abnormalities.

PMID- 29218410
TI  - Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and
      involves nitric oxide production via Akt activation in mice.
AB  - Studies have demonstrated that thyroid hormone (T3) can precondition the heart
      against ischaemic injury and improve post-ischaemic recovery. This study
      investigated whether the AT2 receptor (AT2R) is involved in cardioprotection and
      the potential molecular mechanism responsible for this effect. Hyperthyroidism
      was induced in male wild-type (WT) and AT2R knockout (KO) mice by administering
      daily intraperitoneal injections of T3 (7 MUg/100 g body weight) for 14 days. The
      mouse hearts were harvested and perfused with a Krebs-Henseleit solution at a
      constant flow in a Langendorff set-up. After 30 min of stabilization, the hearts
      were subjected to global ischaemia for 20 min and reperfused for 45 min. Baseline
      cardiac function was assessed by measuring four parameters: LVDP (mmHg), heart
      rate (bpm), + dP/dt and - dP/dt (mmHg/s). After reperfusion, the total protein
      from cardiac ventricles was obtained, and the Akt signalling pathway and NO
      production were evaluated. Post-ischaemic functional recovery was significantly
      greater (p < 0.05) in the T3-treated WT mice compared to the control,
      demonstrating the cardioprotective effect of T3. This effect was abolished in T3
      treated KO mice, demonstrating the physiological relevance of AT2R to the
      cardioprotective phenotype induced by T3. Akt activation, iNOS expression and NO
      production increased in cardiac tissue after T3 treatment in the WT animals, but
      no difference was observed after treatment in the KO mice. This study indicates
      that AT2R acts as a cardioprotector in the case of hyperthyroidism. Strategies
      targeting AT2R agonists might improve cardiac function through NO production and
      suggest potential therapeutic targets for heart diseases.

PMID- 29218412
TI  - Epilepsy surgery in infants : Safety issues and developmental outcome.
AB  - PURPOSE: To evaluate the efficacy and safety of epilepsy surgery in infants.
      METHODS: Included were patients with epilepsy onset during the first year of
      life, epilepsy surgery before the age of 36 months at the study center and a
      minimum follow-up of 24 months after surgery. Patients who were surgically
      treated before the age of 12 months were compared with those between 13 and 36
      months. Group differences with respect to efficacy (seizure outcomes and
      developmental progress measured by the social interaction quotient, SIQ) as well
      as safety (i. e. peri-operative complication rates) were analyzed. RESULTS: A
      total of 20 patients (10 girls) were included: 10 (five girls) were operated on
      as infants (median age at surgery 9.0 months, median disease duration prior to
      surgery 5.0 months) and 10 (5 girls) were operated on as toddlers (median age at
      surgery 24.0 months, median disease duration prior to surgery 18.0 months).
      Favorable seizure outcomes (Wieser 1a and 1) were seen in 80% (8/10) of the
      infants and 60.0% (6/10) of toddlers. Developmental progress was most evident in
      infants who were seizure-free and off medication (median SIQ 85.5 versus 63.0 in
      the toddler group). There were no differences between the two groups with respect
      to safety aspects. CONCLUSION: Despite several limitations due to the small
      number of patients included, our results are in favor of early epilepsy surgery
      in infants with drug-resistant epilepsy.

PMID- 29218413
TI  - Do free-ranging rattlesnakes use thermal cues to evaluate prey?
AB  - Rattlesnakes use infrared radiation to detect prey animals such as small mammals
      and lizards. Because ectotherm locomotor performance depends on temperature,
      rattlesnakes could use prey temperature to evaluate the potential of lizards to
      evade attacks. Here, we tested whether hunting rattlesnakes use infrared
      information to (1) detect and (2) evaluate prey before attack. We expected
      thermal contrast between prey and background to be the best predictor of
      predatory behaviour under the prey detection hypothesis, and absolute prey
      temperature under the prey evaluation hypothesis. We presented lizard carcasses
      of varying temperatures to free-ranging sidewinder rattlesnakes (Crotalus
      cerastes) and scored behavioural responses as a function of thermal contrast,
      absolute lizard temperature, and light level. Thermal contrast and light level
      were the most salient predictors of snake behaviour. Snakes were more likely to
      respond to lizards and/or respond at greater distances at night and when thermal
      contrast was high, supporting the known prey detection function of infrared
      sensing. Absolute lizard temperature was not an important predictor of snake
      behaviour; thus, we found no evidence for temperature-based prey evaluation.
      Infrared sensing is still poorly understood in ecologically relevant contexts;
      future research will test whether rattlesnakes learn to evaluate prey based on
      temperature with experience.

PMID- 29218414
TI  - Cyclic lipopeptide signature as fingerprinting for the screening of halotolerant
      Bacillus strains towards microbial enhanced oil recovery.
AB  - Cyclic lipopeptides (CLPs) are non-ribosomal biosurfactants produced by Bacillus
      species that exhibit outstanding interfacial activity. The synthesis of CLPs is
      under genetic and environmental influence, and representatives from different
      families are generally co-produced, generating isoforms that differ in chemical
      structure and biological activities. This study to evaluate the effect of low and
      high NaCl concentrations on the composition and surface activity of CLPs produced
      by Bacillus strains TIM27, TIM49, TIM68, and ICA13 towards microbial enhanced oil
      recovery (MEOR). The strains were evaluated in mineral medium containing NaCl
      2.7, 66, or 100 g L-1 and growth, surface tension and emulsification activity
      were monitored. Based on the analysis of 16S rDNA, gyrB and rpoB sequences TIM27
      and TIM49 were assigned to Bacillus subtilis, TIM68 to Bacillus vallismortis, and
      ICA13 to Bacillus amyloliquefaciens. All strains tolerated up to 100-g L-1 NaCl,
      but only TIM49 and TIM68 were able to reduce surface tension at this
      concentration. TIM49 also showed emulsification activity at concentrations up to
      66-g L-1 NaCl. ESI-MS analysis showed that the strains produced a mixture of
      CLPs, which presented distinct CLP profiles at low and high NaCl concentrations.
      High NaCl concentration favored the synthesis of surfactins and/or fengycins that
      correlated with the surface activities of TIM49 and TIM68, whereas low
      concentration favored the synthesis of iturins. Taken together, these findings
      suggest that the determination of CLP signatures under the expected condition of
      oil reservoirs can be useful in the guidance for choosing well-suited strains to
      MEOR.

PMID- 29218415
TI  - Timing of cortical activation during spontaneous swallowing.
AB  - Saliva accumulation in the oropharynx generates an automatic pattern of
      swallowing in the brainstem in animals. Previous fMRI studies have found that
      spontaneous saliva and water swallows in humans evoked activation following
      swallow onset in both precentral motor and postcentral somatosensory cortical
      regions. Using event-related averaging of continuous functional near infrared
      spectroscopy (fNIRS), we examined cortical hemodynamic responses (HDR) from 5 s
      before to 35 s after spontaneous reflexive saliva swallow onset in the lateral
      postcentral somatosensory and precentral motor regions in both hemispheres in
      healthy volunteers. Three HDR changes from baseline were detected. First, the
      onset of HDR occurred 2 s before swallow onset in the left postcentral
      somatosensory area and 0.67 s before swallow onset in the right postcentral
      somatosensory area. Second, an early HDR peak amplitude occurred 3-4 s after
      swallow onset in all four regions. Z scores relative to baseline pre-swallow
      cortical activity levels averaged 20 and 22.7 s in the right and left
      somatosensory regions and 10 and 15.8 s in left and right motor areas,
      respectively. Finally, a late HDR peak occurring between 22 and 23 s after
      swallow onset in the somatosensory regions and 17-19 s in the motor areas likely
      resulted from esophageal peristalsis. Overall, cortical activation timing
      relative to swallow onsets showed activation began before the pharyngeal phase of
      swallowing in the somatosensory areas. This indicates that somatosensory
      triggering of swallowing occurs not only in the brainstem but also in the cortex
      for reflexive saliva swallowing in awake humans.

PMID- 29218416
TI  - Stability and donor-acceptor bond in dinuclear organometallics CpM1-M2Cl3 (M1, M2
      = B, Al, Ga, In; Cp = eta 5-C5H5).
AB  - The geometries and stabilities of the dinuclear organometallics CpM1-M2Cl3 (M1,
      M2 = B, Al, Ga, In; Cp = eta 5-C5H5) have been investigated by density functional
      theory (DFT) at M06 L/6-311G(d, p) levels. The nature of the donor-acceptor M1 ->
      M2 bond was also studied based on the atoms in molecules (AIM) theory, energy
      decomposition analysis (EDA) and natural bond orbital (NBO) analysis. The results
      show that the electronegativity of the M atom determines the stability and
      covalent character of the dinuclear organometallics CpM1-M2Cl3. The compounds in
      which the M with larger electronegativity acts as the donor are more stable than
      in those in which it acts as the acceptor in the donor-acceptor bond, and the
      donor-acceptor bond has more covalent characteristics. The strength and polarity
      of the M1 -> M2 donor-acceptor bond is determined by the periodicity of the M
      atom. When the period number of the M1 atom is smaller than that of M2, the
      strength of the M1 -> M2 bond is larger than that of the M2 -> M1 bond. For
      homonuclear dinuclear organometallics, the polarity of the M-M bond increases
      with increasing atomic number of the M atom. For heteronuclear complexes, the
      polarity of the M1-M2 bond for a given M1 also increases in the sequence of M2 =
      B, Al, Ga, and In. Graphic abstract Molecular graph and electron location
      function isosurfaces map of CpM 1 -M 2 Cl 3(small red spheres represent bond
      critical points).

PMID- 29218417
TI  - Intensive dietary intervention promoting the Mediterranean diet in people with
      high cardiometabolic risk: a non-randomized study.
AB  - AIMS: Mediterranean diet (MD) is acknowledged to exert a number of beneficial
      health effects. We assessed the efficacy and the durability of a 3-month
      intensive dietary intervention aimed at implementing the MD on body weight and
      cardiometabolic risk factors in subjects at high risk. METHODS: One hundred and
      sixteen subjects participated in the study (71 assigned to the intensive
      intervention and 45 to the conventional intervention). The intensive intervention
      consisted of 12 weekly group educational meetings and a free-of-charge supply of
      meals prepared according to the MD model. The conventional intervention consisted
      of an individual education session along with monthly reinforcements of
      nutritional messages by the general practitioner. All participants were followed
      up for 9 months. RESULTS: The two groups had similar pre-intervention
      characteristics. After the intervention, mean body weight decreased significantly
      in both groups (p < 0.001). However, the intervention group lost more weight (6.8
      +/- 4.0 vs. 0.7 +/- 1.3, p < 0.0001) and showed a greater reduction in plasma
      glucose, triglycerides, blood pressure and an increase in HDL cholesterol than
      the control group (p < 0.01-p < 0.002). In the subgroup of participants with type
      2 diabetes, there was a significant reduction in HbA1c level following the
      intensive (p < 0.0001) but not the conventional intervention. At follow-up,
      weight loss still persisted in the intervention group (p < 0.0001), while it was
      lost in the control group. Both interventions significantly reduced blood
      pressure in the long term (p < 0.001). A significant reduction in daily total
      energy intake was observed in both groups with a greater reduction in saturated
      fat and a higher increase in fibre intake in the intervention than in the control
      group (p < 0.009 and p < 0.001, respectively). CONCLUSIONS: A 3-month intensive
      dietary intervention inspired to the traditional MD produced greater and more
      durable weight loss and improvement in cardiometabolic risk profile than the
      conventional intervention.

PMID- 29218418
TI  - Agricultural water policy reforms in China: a representative look at Zhangye
      City, Gansu Province, China.
AB  - Water resources are essential for agricultural production in the grain-producing
      region of China, and water shortage could significantly affect the production and
      international trade of agricultural products. China is placing effort in new
      policies to effectively respond to changes in water resources due to changes in
      land use/land cover as well as climatic variations. This research investigates
      the changes in land, water, and the awareness of farmer vis-a-vis the
      implementation of water-saving policies in Zhangye City, an experimental site for
      pilot programs of water resources management in China. This research indicates
      that the water saved through water-saving programs and changes in cropping
      structure (2.2 * 108 m3 a-1) is perhaps lower than the newly increased water
      withdrawal through corporate-led land reclamation (3.7 * 108 m3 a-1). Most
      critically, the groundwater withdrawal has increased. In addition, our survey
      suggests that local government is facing a dilemma of water conservation and
      agricultural development. Therefore, the enforcement of the ban on farmland
      reclamation and irrigation water quotas in our study area is revealed to be
      relatively loose. In this vein, the engagement of local stakeholders in water
      governance is essential for the future sustainable management of water resources.

PMID- 29218419
TI  - An unexpected improvement in spatial learning and memory ability in alpha
      synuclein A53T transgenic mice.
AB  - Growing evidence suggests, as Parkinson's disease (PD) progresses, that its non
      motor symptoms appear prior to or in parallel with its motor deficits. Alpha
      synuclein A53T transgenic mouse (A53T) is an essential tool to investigate the
      onsets and the extents of PD non-motor symptoms. Our aim is to investigate
      spatial learning and memory ability in A53T mice. In our rotarod tests, no motor
      coordination impairments were detected in mice of 3, 6, 9, and 12 months old. We
      then investigated their spatial learning and memory ability through Morris water
      maze in 3- and 9-month-old mice. No significant difference in escape latency was
      detected among the A53T mice and the control mice. However, an unexpected
      improvement in spatial learning and memory ability was observed in the probe
      session among the A53T mice. Reversal learning by Morris water maze also
      indicated that 3- and 9-month-old A53T mice exhibited a better cognitive
      flexibility compared to their littermate controls. Further studies by western
      blots showed that alpha-synuclein expressions in hippocampus of the A53T mice
      were noticeably up-regulated. The immunofluorescence staining of 5-bromo-2
      deoxyuridine (Brdu) and doublecortin (DCX) demonstrated that neither the Brdu
      positive neurons nor the Brdu/DCX positive neurons in hippocampus were
      significantly altered between the two groups. These results suggest that our A53T
      mice exhibit improved spatial learning and memory ability prior to their motor
      coordination deficits. These results are not induced by neurogenesis in the
      hippocampus.

PMID- 29218420
TI  - An Improved Pathological Brain Detection System Based on Two-Dimensional PCA and
      Evolutionary Extreme Learning Machine.
AB  - Pathological brain detection has made notable stride in the past years, as a
      consequence many pathological brain detection systems (PBDSs) have been proposed.
      But, the accuracy of these systems still needs significant improvement in order
      to meet the necessity of real world diagnostic situations. In this paper, an
      efficient PBDS based on MR images is proposed that markedly improves the recent
      results. The proposed system makes use of contrast limited adaptive histogram
      equalization (CLAHE) to enhance the quality of the input MR images. Thereafter,
      two-dimensional PCA (2DPCA) strategy is employed to extract the features and
      subsequently, a PCA+LDA approach is used to generate a compact and discriminative
      feature set. Finally, a new learning algorithm called MDE-ELM is suggested that
      combines modified differential evolution (MDE) and extreme learning machine (ELM)
      for segregation of MR images as pathological or healthy. The MDE is utilized to
      optimize the input weights and hidden biases of single-hidden-layer feed-forward
      neural networks (SLFN), whereas an analytical method is used for determining the
      output weights. The proposed algorithm performs optimization based on both the
      root mean squared error (RMSE) and norm of the output weights of SLFNs. The
      suggested scheme is benchmarked on three standard datasets and the results are
      compared against other competent schemes. The experimental outcomes show that the
      proposed scheme offers superior results compared to its counterparts. Further, it
      has been noticed that the proposed MDE-ELM classifier obtains better accuracy
      with compact network architecture than conventional algorithms.

PMID- 29218421
TI  - Cistus ladanifer (Cistaceae): a natural resource in Mediterranean-type
      ecosystems.
AB  - MAIN CONCLUSION: Cistus ladanifer has a well-defined taxonomic identity. 2,2,6
      trimethylcyclohexanone may be an authenticity and taxonomic marker. Its traits
      and applications make it a possible economic resource fitted for Mediterranean
      areas. Cistus ladanifer is a dominant shrub species endemic to the western
      Mediterranean region. Due to its dominant nature and its potential ecological,
      aromatic or pharmacological applications, C. ladanifer has been the object of
      numerous studies. In this review current knowledge on different aspects of this
      species is summarized, from its taxonomy to its chemical characterisation or its
      competitive traits. There are no doubts about the taxonomic entity of C.
      ladanifer, although the recognition of infraspecific taxa deserves more
      attention. Given that the fragrant exudate of C. ladanifer holds a very specific
      composition, one species specific carotenoid, 2,2,6-trimethylcyclohexanone,
      derivative is proposed as an authenticity marker for uses of C. ladanifer in
      pharmacological or aromatic industries. Evidence is also gathered on the extreme
      adaptation of C. ladanifer to stressful conditions in the Mediterranean region,
      such as the ability to survive in low hydric and high solar exposition
      conditions, presistence in poor and contaminated soils, and growth inhibition of
      several other plants through the release of allelochemicals. Thus, the finding of
      potential applications for this plant may contribute to enhance the economic
      dimension of derelict lands, such as mine tailings or poor agricultural
      Mediterranean areas.

PMID- 29218422
TI  - How frequent does peri-implantitis occur? A systematic review and meta-analysis.
AB  - OBJECTIVES: The objective of this study is to estimate the overall prevalence of
      peri-implantitis (PI) and the effect of different study designs, function times,
      and implant surfaces on prevalence rate reported by the studies adhering to the
      case definition of Sanz & Chapple 2012. MATERIAL AND METHODS: Following
      electronic and manual searches of the literature published up to February 2016,
      data were extracted from the studies fitting the study criteria. Meta-analysis
      was performed for estimation of overall prevalence of PI while the effects of the
      study design, function time, and implant surface type on prevalence rate were
      investigated using meta-regression method. RESULTS: Twenty-nine articles were
      included in this study. The prevalence rate in all subset meta-analyses was
      always higher at patient level when compared to the prevalence rate at the
      implant level. Prevalence of PI was 18.5% at the patient level and 12.8% at the
      implant level. Meta-regression analysis did not identify any association for
      different study designs and function times while it was demonstrated the
      significant association between moderately rough surfaces with lower prevalence
      rate of PI (p = 0.011). CONCLUSIONS: The prevalence rate of PI remains highly
      variable even following restriction to the clinical case definition and it seems
      to be affected by local factors such as implant surface characteristics. The
      identification of adjuvant diagnostic markers seems necessary for more accurate
      disease classification. CLINICAL RELEVANCE: The occurrence of PI is affected by
      local factors such as implant surface characteristics hence the careful
      assessment of the local factors should be performed within treatment planning.

PMID- 29218423
TI  - Early intraocular pressure change after peripheral iridotomy with ultralow
      fluence pattern scanning laser and Nd:YAG laser in primary angle-closure suspect:
      Kowloon East Pattern Scanning Laser Study Report No. 3.
AB  - PURPOSE: Our purpose was to assess the early intraocular pressure (IOP) changes
      of ultralow fluence laser iridotomy using pattern scanning laser followed by
      neodymium:yttrium-aluminum-gamet (Nd:YAG) laser. METHODS: This is a prospective
      interventional study. Thirty-three eyes of 33 adult Chinese primary angle-closure
      suspect subjects were recruited for prophylactic laser peripheral iridotomy.
      Sequential laser peripheral iridotomy was performed using pattern scanning laser
      followed by Nd:YAG laser. Visual acuity (VA) and IOP were measured before
      treatment, at 1 h, 1 day, 1 week, 1 month, 3 months and 6 months after laser.
      Laser energy used and complications were documented. Corneal endothelial cell
      count was examined at baseline and 6 months. Patency of the iridotomy was
      assessed at each follow-up visit. RESULTS: All subjects achieved patent iridotomy
      in a single session. The mean energy used was 0.335+/-0.088 J for the pattern
      scanning laser, and 4.767+/-5.780 mJ for the Nd:YAG laser. The total mean energy
      was 0.339+/-0.089 J. None of the eyes developed a clinically significant IOP
      spike (>= 8 mmHg) at 1 h and 1 day after laser use. Only four eyes developed
      higher IOP at 1 h and all were <=3 mmHg compared to baseline. The mean IOP was
      13.8+/-2.5 mmHg at 1 h and 11.5+/-2.2 mmHg at 1 day, both were significantly
      lower than baseline (15.8+/-2.1 mmHg) (P < 0.001). Mean VA (logMAR) was similar
      at 1 h post laser compared to baseline (0.23 vs 0.26). There was also no
      statistically significant difference in mean VA at other follow-up visits
      compared to baseline. Peripheral iridotomy closure was encountered in two (6.1%)
      eyes, one at 1 month and another at 6 months follow-up. There were no
      complications including hyphema, peripheral anterior synechia formation nor
      prolonged inflammation throughout the follow-up period. There was no significant
      loss in corneal endothelial cell counts at 6 months (2255+/-490) compared to
      baseline (2303+/-386) (P = 0.347). CONCLUSIONS: Sequential LPI using an ultralow
      fluence pattern scanning laser, followed by a Nd:YAG laser, is safe and
      efficacious, and produces no IOP spike in dark irides of primary angle-closure
      suspects. Further studies to investigate its role in the treatment of other angle
      closure conditions are warranted.

PMID- 29218424
TI  - Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT)
      Substrates After Intranasal (IN) Administration.
AB  - To illustrate the use of imaging to quantify the transfer of materials from the
      nasal cavity to other anatomical compartments, specifically, transfer to the
      brain using the thymidine analogue, [18F]fluorothymidine (FLT), and the glucose
      analogue, [18F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT
      or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT
      imaging was performed for up to 60 min. Volumes-of-interest (VOIs) for the
      olfactory bulb (OB) and the remaining brain were created on the CT and
      transferred to the co-registered dynamic PET. Time-activity curves (TACs) were
      generated and compared. The disposition patterns were successfully visualized and
      quantified and differences in brain distribution patterns were observed. For FDG,
      the concentration was substantially higher in the OB than the brain only after IN
      administration. For FLT, the concentration was higher in the OB than the brain
      after both IN and IV and higher after IN than after IV administration at all
      times, whereas the concentration in the brain was higher after IN than after IV
      administration at early times only. Approximately 50 and 9% of the IN FDG and FLT
      doses, respectively, remained in the nasal cavity at 20 min post-administration.
      The initial phase of clearance was similar for both agents (t1/2 = 2.53 and 3.36
      min) but the slow clearance phase was more rapid for FLT than FDG (t1/2 = 32.1
      and 85.2 min, respectively). Pharmacoimaging techniques employing PET/CT can be
      successfully implemented to quantitatively investigate and compare the
      disposition of radiolabeled agents administered by a variety of routes.

PMID- 29218425
TI  - Ionized and total serum magnesium in hemodialysis: predictors and variability. A
      longitudinal cross-sectional study.
AB  - BACKGROUND: Ionized Magnesium (ion-Mg) represents the active biological fraction
      of the serum magnesium content. The assessment of total serum Mg (tot-Mg) might
      not accurately identify patients with hypo-or hyper-magnesaemie. In hemodialysis,
      serum tot-Mg levels in the upper part of the distribution, have been associated
      with reduced mortality and fewer vascular calcifications; thus, resulting in the
      tendency to increase the Mg concentration in the dialysate, traditionally set at
      0.5 mmol/L. METHODS: Single-center study in chronic hemodialysis patients,
      designed in two phases, cross-sectional and longitudinal, aimed to investigate:
      (1) the sensitivity for pathological values of ion-Mg compared to tot-Mg (2) the
      predictors of ion-Mg developing ad hoc equations; (3) the inter- and intra
      individual variabilities of ion-Mg; and (4) the risk factors for hypermagnesemia.
      Tot-Mg, ion-Mg, and covariates of 42 hemodialysis sessions, in 42 patients during
      the cross-sectional phase and of 270 sessions in 27 patients in the longitudinal
      one were analysed. RESULTS: Ion-Mg significantly correlates with tot-Mg: beta =
      0.52; r = 0.88, p < 0.001. Multiple linear regressions in normo- and hypo
      albuminemic patients gave the following results: ion-Mg = tot-Mg/2-K+/50 + Ca2+/5
      HCO3-/100 and ion-Mg = tot-Mg/2 + albumin/100. Ion-Mg showed a high temporal
      variability in the longitudinal phase (between months p < 0.001; winter vs.
      summer, p < 0.027). A high intra-individual variability was also found:
      coefficient of variation 0.116. Comparing patients with high and low intra
      individual variability, we found: age 67 vs. 77 years; p < 0.001; urea 26.3 +/-
      0.5 vs. 21.2 +/- 0.4 mmol/L, p < 0.001; nPCR 0.92 +/- 0.1 vs. 0.77 +/- 0.1 g/kg
      day, p < 0.001; PTH 46.3 +/- 4 vs. 28.5 +/- 3 pmol/L, p < 0.001. CONCLUSIONS: Ion
      Mg can be useful in unmasking unrecognized hyper- and hypo-magnesemic and false
      hyper-magnesemic patients. Ion-Mg is characterized by high intra- and inter
      individual variabilities particularly in younger women and those with better
      nutrition. Patients with greater variability could potentially be at risk if
      exposed to higher concentrations of magnesium in the dialysate. An interventional
      study, with controlled increase of magnesium concentrations in the dialysate has
      been planned.

PMID- 29218427
TI  - The role of nonautologous and autologous adipose-derived mesenchymal stem cell in
      acute pyelonephritis.
AB  - We compared the therapeutic effects of autologous and nonautologous adipose
      derived mesenchymal stem cell (ADMSC), in ameliorating the renal function in a
      rabbit model of acute pyelonephritis. The difference of perirenal and neck
      subcutaneous ADMSCs were also evaluated. Twenty female rabbits were apportioned
      to 5 groups. In group I (n = 4), the rabbits were injected direct inoculation of
      Escherichia coli (E. coli) into the right kidney. In group II (n = 4), autologous
      ADMSCs obtained from nape adipose tissue were injected into the subcapsular space
      1 week after E. coli injection, while nonautologous ADMSCs of the same origin
      (from male rabbits) were applied in group III (n = 4). In group IV (n = 4),
      autologous perirenal ADMSCs were applied with the same method, while perirenal
      nonautologous ADMSCs from male rabbits were used in group V (n = 4). Technetium
      99m-DMSA renal scan was performed 1, 2 and 4 months post-injection in all groups.
      Kidneys were excised for the evaluation of histopathological changes in the same
      time points. PCR examination for detection of Y-chromosome (in group III and V)
      and fluorescent evaluation (in group II and IV) were also performed to determine
      the fate of injected cells. Injection of autologous ADMSCs resulted in more
      satisfactory outcomes in reduction of interstitial fibrosis, tubular, and
      glomerular atrophy as compared to nonautologous groups. However,
      histopathological ameliorations were significantly better in group IV in which
      autologous perirenal ADMSC was applied. Remarkably, two months after the
      injection, Technetium-99m-DMSA renal scan showed that right kidney reached to
      near normal cortical function (48 and 45%) in group IV and V, respectively as
      compared to groups II (41%) and III (37%). Autologous ADMSCs may have better
      results in cell therapy as compared to nonautologous cells. However, more
      satisfactory outcomes may be obtained when the cell source is selected from the
      surrounding adipose tissue.

PMID- 29218426
TI  - Telomere length and risk of developing gastric adenocarcinoma: The Singapore
      Chinese Health Study.
AB  - BACKGROUND: Extreme telomere length has been previously reported to be associated
      with increased risk of gastric cancer. However, evidence from prospective studies
      on a relative large sample size with long-term follow-up to further corroborate
      previous study findings is meager. METHODS: The association between peripheral
      blood leukocyte telomere length and risk of gastric adenocarcinoma was
      prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested
      in the Singapore Chinese Health Study. Telomere length was determined using a
      validated qPCR-based method. The Cox proportional regression method was used to
      estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric
      adenocarcinoma associated with telomere length after adjustment for potential
      confounders. Restricted cubic spline analysis was applied to assess the nonlinear
      relationship between telomere length and gastric cancer risk. RESULTS: A U-shaped
      association was found between telomere length and risk of gastric adenocarcinoma
      (P nonlinearity = 0.020). Compared with the second quintile of telomere length, a
      statistically significant higher risk of gastric adenocarcinoma was associated
      with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest
      quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped
      relationship was more apparent in men and younger individuals. CONCLUSIONS: This
      is the first prospective study demonstrating a higher risk of gastric cancer to
      be associated with either extremely short or extremely long telomere length.
      Short and long telomere length may function differently in the early and late
      stages of gastric carcinogenesis.

PMID- 29218428
TI  - SPECT/CT: Looking Beyond Sentinel Lymph Node Identification for Improving Patient
      Outcomes.

PMID- 29218429
TI  - Protein Expression of PTTG1 as a Diagnostic Biomarker in Adrenocortical
      Carcinoma.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) has a poor prognosis and there is an
      unmet clinical need for biomarkers to improve both diagnostic and prognostic
      assessment. Pituitary-tumor transforming gene (PTTG1) has been shown to modulate
      cancer invasiveness and response to therapy. The potential role of PTTG1 protein
      levels in ACC has not been previously addressed. We assessed whether increased
      nuclear protein expression of PTTG1 distinguished ACCs from adrenocortical
      adenomas (ACAs). METHODS: Patients with ACC or ACA were identified from
      prospective tissue banks at two independent institutions. Two tissue microarrays
      (TMAs) consisting of adrenal specimens from 131 patients were constructed and
      clinically annotated. Immunohistochemical analysis for PTTG1 and Ki-67 was
      performed on each TMA. RESULTS: TMA-1 (n = 80) contained 20 normal adrenals, 20
      ACAs, and 40 ACCs, and the validation, TMA-2 (n = 51), consisted of 10 normal
      adrenals, 14 ACAs, and 27 ACCs. On TMA-1, nuclear staining of PTTG1 was detected
      in 12 (31%) ACC specimens, while all ACAs and normal adrenal glands were negative
      for PTTG1. On TMA-2, 20 (74%) of the ACC tumors demonstrated PTTG1 nuclear
      staining of PTTG1, and 13 (93%) ACA and 4 (44%) normal adrenal glands were
      negative for PTTG1. ACC tumors with increased PTTG1 protein staining had a
      significantly higher Ki-67 index (p < 0.001) than those with lower levels of
      PTTG1. CONCLUSIONS: Increased nuclear protein expression of PTTG1 was observed in
      malignant adrenal tumors. PTTG1 correlated with Ki-67 in two independent TMAs.
      PTTG1 is a promising biologic marker in the evaluation of adrenal tumors.

PMID- 29218430
TI  - CPdock: the complementarity plot for docking of proteins: implementing multi
      dielectric continuum electrostatics.
AB  - The complementarity plot (CP) is an established validation tool for protein
      structures, applicable to both globular proteins (folding) as well as protein
      protein complexes (binding). It computes the shape and electrostatic
      complementarities (Sm, Em) for amino acid side-chains buried within the protein
      interior or interface and plots them in a two-dimensional plot having knowledge
      based probabilistic quality estimates for the residues as well as for the whole
      structure. The current report essentially presents an upgraded version of the
      plot with the implementation of the advanced multi-dielectric functionality (as
      in Delphi version 6.2 or higher) in the computation of electrostatic
      complementarity to make the validation tool physico-chemically more realistic.
      The two methods (single- and multi-dielectric) agree decently in their resultant
      Em values, and hence, provisions for both methods have been kept in the software
      suite. So to speak, the global electrostatic balance within a well-folded protein
      and/or a well-packed interface seems only marginally perturbed by the choice of
      different internal dielectric values. However, both from theoretical as well as
      practical grounds, the more advanced multi-dielectric version of the plot is
      certainly recommended for potentially producing more reliable results. The report
      also presents a new methodology and a variant plot, namely CPdock, based on the
      same principles of complementarity specifically designed to be used in the
      docking of proteins. The efficacy of the method to discriminate between good and
      bad docked protein complexes has been tested on a recent state-of-the-art docking
      benchmark. The results unambiguously indicate that CPdock can indeed be effective
      in the initial screening phase of a docking scoring pipeline before going into
      more sophisticated and computationally expensive scoring functions. CPdock has
      been made available at https://github.com/nemo8130/CPdock . Graphical Abstract An
      example showing the efficacy of CPdock to be used in the initial screening phase
      of a protein-protein docking scoring pipeline.

PMID- 29218431
TI  - External validity of two nomograms for predicting distant brain failure after
      radiosurgery for brain metastases in a bi-institutional independent patient
      cohort.
AB  - Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM)
      are at increased risk of distant brain failure (DBF). Two nomograms have been
      recently published to predict individualized risk of DBF after SRS. The goal of
      this study was to assess the external validity of these nomograms in an
      independent patient cohort. The records of consecutive patients with BM treated
      with SRS at Levine Cancer Institute and Emory University between 2005 and 2013
      were reviewed. Three validation cohorts were generated based on the specific
      nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest
      nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303)
      validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30%
      compared with 50% in the validation cohort. The validation c-index for both the 6
      month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating
      poor discrimination ability, and the goodness-of-fit test for both nomograms was
      highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial
      DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the
      validation cohort. The validation c-index for the Canadian 1-year DBF nomogram
      was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001).
      The validation accuracy and c-index of the Canadian RPA classification was 53%
      and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting
      risk of DBF after SRS were found to have limited predictive ability in an
      independent bi-institutional validation cohort. These results reinforce the
      importance of validating predictive models in independent patient cohorts.

PMID- 29218432
TI  - The 2016 revision of the WHO Classification of Central Nervous System Tumours:
      retrospective application to a cohort of diffuse gliomas.
AB  - The classification of central nervous system tumours has more recently been
      shaped by a focus on molecular pathology rather than histopathology. We re
      classified 82 glial tumours according to the molecular-genetic criteria of the
      2016 revision of the World Health Organization (WHO) Classification of Tumours of
      the Central Nervous System. Initial diagnoses and grading were based on the
      morphological criteria of the 2007 WHO scheme. Because of the impression of an
      oligodendroglial component on initial histological assessment, each tumour was
      tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate
      dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded
      by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was
      assessed by immunohistochemistry. We found that all but two tumours could be
      assigned to a specific category in the 2016 revision. The most common change in
      diagnosis was from oligoastrocytoma to specifically astrocytoma or
      oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II
      and III tumours showed that the objective criteria of the 2016 revision separated
      diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co
      deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant
      difference in PFS was found when comparing IDH mutant grade II and III tumours
      suggesting that IDH status is more informative than tumour grade. The segregation
      into distinct molecular sub-types that is achieved by the 2016 revision provides
      an objective evidence base for managing patients with grade II and III diffuse
      gliomas based on prognosis.

PMID- 29218434
TI  - Inhibition of GSK-3beta Signaling Pathway Rescues Ketamine-Induced Neurotoxicity
      in Neural Stem Cell-Derived Neurons.
AB  - Clinical application of anesthetic reagent, ketamine (Keta), may induce
      irreversible neurotoxicity in central nervous system. In this work, we utilized
      an in vitro model of neural stem cells-derived neurons (nSCNs) to evaluate the
      role of GSK-3 signaling pathway in Keta-induced neurotoxicity. Embryonic mouse
      brain neural stem cells were differentiated into neurons in vitro. Keta (50 MUM)
      induced neurotoxicity in cultured nSCNs was monitored by apoptosis,
      immunohistochemical and western blot assays, respectively. GSK-3 signaling
      pathways, including GSK-3alpha and GSK-3beta, were inhibited by siRNA in the
      culture. The subsequent effects of GSK-3alpha or GSK-3beta downregulation on Keta
      induced neurotoxicity, including apoptosis and neurite loss, were then evaluated
      in nSCNs. Finally, caspase and Akt/ERK signal pathways were further examined by
      western blot to evaluate the regulatory effect of GSK-3 signaling pathways on
      Keta-induced neural injury. Keta (50 MUM) caused markedly nSCN apoptosis and
      neurite degeneration in vitro. Keta decreased GSK-3beta phosphorylation, but had
      no effect on GSK-3alpha phosphorylation. SiRNA-induced GSK-3beta downregulation
      rescued Keta-induced neurotoxicity in nSCNs by reducing neuronal apoptosis and
      preventing neurite degeneration. On the other hand, GSK-3alpha downregulation had
      no effect on Keta-induced neurotoxicity. Western blot showed that, in Keta
      injured nSCNs, GSK-3beta downregulation reduced Caspase-1/3 proteins, but left
      phosphorylated Akt/ERK unchanged. GSK-3beta, not GSK-3alpha, was specifically
      involved in the process of Keta-induced neurotoxicity in nSCNs. Inhibiting GSK
      3beta may be an effective approach to counter toxic effect of ketamine on central
      neurons in clinical and experimental applications.

PMID- 29218433
TI  - s8ORF2 protein of infectious salmon anaemia virus is a RNA-silencing suppressor
      and interacts with Salmon salar Mov10 (SsMov10) of the host RNAi machinery.
AB  - The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of
      Orthomyxoviridae family. It encodes at least 10 proteins from eight negative
      strand RNA segments. Since ISAV belongs to the same virus family as Influenza A
      virus, with similarities in protein functions, they may hence be characterised by
      analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in
      interferon antagonism and RNA-binding functions. In this study, we investigated
      the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium
      transient suppression assay in stably silenced transgenic Nicotiana xanthi. In
      addition, s8ORF2 was identified as a novel interactor with SsMov10, a key
      molecule responsible for RISC assembly and maturation in the RNAi pathway. This
      study thus sheds light on a novel route undertaken by viral proteins in promoting
      viral growth, using the host RNAi machinery.

PMID- 29218436
TI  - Peritoneal dialysis and infants: further insights into a complicated
      relationship.
AB  - Peritoneal dialysis (PD) in infants represents one of the greatest challenges for
      pediatric nephrologists. Over recent years, positive outcome data described by
      several multicenter experiences and registry studies have increased the amount of
      information available to help determine whether to initiate a dialysis program in
      this high-risk patient population. There is no doubt that the rigorous
      implementation of strategies aimed at preventing infectious complications may
      have contributed to reducing the morbidity rate of these patients. However, the
      complex nature of infants with end-stage renal disease and the presence of
      multiple comorbidities still represent hallmarks that significantly impact on
      outcome. Although the rigorous application of improved scientific techniques can
      still contribute to enhancing PD results in infants, we have to acknowledge that
      the severity of illness in infants, especially at dialysis initiation, represents
      an undeniable and nonmodifiable factor.

PMID- 29218435
TI  - Educational review: measurement of GFR in special populations.
AB  - IMPORTANCE: Changes in kidney function are typically followed by the sequential
      estimation of glomerular filtration rate (eGFR). Formulae for eGFR work well on a
      population basis, but there are well-known conditions where they do not work.
      OBJECTIVE: The purpose of this review is to summarize the existing literature on
      special populations in the pediatric age range and provide recommendations on how
      to estimate GFR in these populations. FINDINGS: The reliability of creatinine
      depends on muscle mass, while cystatin C (not widely available) is limited by
      inflammation and changes in protein catabolism. Various dietary factors can alter
      eGFR. Renal function in neonates changes drastically every day, and there are
      currently no satisfactory reference intervals for routine pediatric use. Gender
      effects and conditions such as wasting disease and obesity require alternative
      ways to obtain eGFR. In oncology patients, chemotherapy may negatively affect
      renal function, and nuclear GFR measurements may be necessary. For body builders,
      high muscle mass may lead to underestimation of eGFR using creatinine.
      CONCLUSIONS AND RELEVANCE: Clinicians should be aware of special populations that
      may yield misleading eGFRs with conventional creatinine-based formulae, and that
      the alternative methods may be more appropriate for some populations.

PMID- 29218437
TI  - D-lactic acidosis in humans: systematic literature review.
AB  - BACKGROUND: D-lactic acidosis is an uncommon and challenging form of metabolic
      acidosis that may develop in short bowel syndrome. It has been documented
      exclusively in case reports and small case series. METHODS: We performed a review
      of the literature in the National Library of Medicine and Excerpta Medica
      databases. RESULTS: We identified 84 original reports published between 1977 and
      2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7
      months to 86 years with short bowel syndrome. The clinical presentation included
      Kussmaul breathing, confusion, slurred speech, and gait disturbances.
      Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported
      having episodes with symptoms consistent with D-lactic acidosis. In addition, D
      lactic acid might also contribute to acidosis in diabetes mellitus. Finally,
      abnormally high D-lactic acid was documented after administration or ingestion of
      large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also
      in a so far poorly characterized inherited inborn error of metabolism.
      CONCLUSIONS: In humans with short bowel syndrome (or carbohydrate malabsorption),
      D-lactic acidosis is likely rather common and under-recognized. This condition
      should be included in the differential diagnosis of unexplained high-gap
      metabolic acidosis where the anion causing the acidosis is not known.
      Furthermore, diabetic acidosis might be caused by accumulation of both ketone
      bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid
      in subjects with propylene glycol intoxication.

PMID- 29218438
TI  - Two novel bocaparvovirus species identified in wild Himalayan marmots.
AB  - Bocaparvovirus (BOV) is a genetically diverse group of DNA viruses and a possible
      cause of respiratory, enteric, and neurological diseases in humans and animals.
      Here, two highly divergent BOVs (tentatively named as Himalayan marmot BOV,
      HMBOV1 and HMBOV2) were identified in the livers and feces of wild Himalayan
      marmots in China, by viral metagenomic analysis. Five of 300 liver samples from
      Himalayan marmots were positive for HMBOV1 and five of 99 fecal samples from
      these animals for HMBOV2. Their nearly complete genome sequences are 4,672 and
      4,887 nucleotides long, respectively, with a standard genomic organization and
      containing protein-coding motifs typical for BOVs. Based on their NS1, NP1, and
      VP1, HMBOV1 and HMBOV2 are most closely related to porcine BOV SX/1-2
      (approximately 77.0%/50.0%, 50.0%/53.0%, and 79.0%/54.0% amino acid identity,
      respectively). Phylogenetic analysis of these three proteins showed that HMBOV1
      and HMBOV2 formed two distinctly independent branches in BOVs. According to these
      results, HMBOV1 and HMBOV2 are two different novel species in the Bocaparvovirus
      genus. Their identification expands our knowledge of the genetic diversity and
      evolution of BOVs. Further studies are needed to investigate their potential
      pathogenicity and their impact on Himalayan marmots and humans.

PMID- 29218439
TI  - Characterization and expression of lin-28a involved in lin28/let-7signal pathway
      during early development of P. olivaceus.
AB  - Heterochronic lin-28 is a conserved RNA-binding protein that plays a key role in
      the timing of developmental events in organisms. As a crucial heterochronic gene,
      the protein controls developmental events of the second of four larval stages in
      Caenorhabditi elegans. Heterochronic let-7 miRNAs are often present in various
      species and highly conserved in sequence and biological function and are required
      for various biological processes. Previous studies showed that ten let-7 miRNAs
      were identified in the Japanese flounder (Paralichthys olivaceus) and that they
      were primarily expressed during metamorphosis. In this study, we clone and
      characterize the lin-28a gene from P. olivaceus and exhibit its dynamic
      expression pattern at different developmental stages and various adult tissues.
      The results show that the P. olivaceus lin-28a gene has high sequence similarity
      with other species and is highly expressed in the embryonic stage but weakly
      expressed in the larval stage. In addition, lin-28a overexpression causes cell
      proliferation and significantly promotes the levels of pre-let-7a and pre-let-7d
      while markedly depressing let-7a and let-7d expression in FEC (Flounder Embryonic
      Cell), which indicate that lin-28 possibly blocks the maturation of let-7 miRNAs.
      Additionally, lin-28a is identified as a target gene of let-7 miRNAs, and let-7
      miRNAs directly regulate lin-28a expression by targeting its 3' UTR. Taken
      together, lin-28a along with let-7 miRNA participates in a lin-28/let-7 axis
      pathway that regulates cell division and timing of embryonic and metamorphic
      events in P. olivaceus.

PMID- 29218441
TI  - Correction to: Do habituation, host traits and seasonality have an impact on
      protist and helminth infections of wild western lowland gorillas?
AB  - Affiliation of Klara J. Petrzelkova was incorrectly assigned as 2, 9, 10 in the
      original version of this article when in fact it should have been 3, 9, 10.
      Correct affiliations are presented here.

PMID- 29218440
TI  - Biochemical properties of the sensitivity to GABAAergic ligands, Cl-/HCO3--ATPase
      isolated from fish (Cyprinus carpio) olfactory mucosa and brain.
AB  - This paper presents a comparative study of the roles of Cl- and HCO3- in the
      functioning of the GABAAR-associated Cl-/HCO3--ATPase of the plasma membranes of
      the olfactory sensory neurons (OSNs) and mature brain neurons (MBNs) of fish. The
      ATPase activity of OSNs and its dephosphorylation were increased twofold by Cl
      (15-30 mmol l-1), whereas the enzyme from MBNs was not significantly affected by
      Cl-. By contrast, HCO3-(15-30 mmol l-1) significantly activated the MBN enzyme
      and its dephosphorylation, but had no effect on the OSN ATPase. The maximum
      ATPase activity and protein dephosphorylation was observed in the presence of
      both Cl-(15 mmol l-1)/HCO3-(27 mmol l-1) and these activities were inhibited in
      the presence of picrotoxin (100 MUmol l-1), bumetanide (150 MUmol l-1), and DIDS
      (1000 MUmol l-1). SDS-PAGE revealed that ATPases purified from the neuronal
      membrane have a subunit with molecular mass of ~ 56 kDa that binds [3H]muscimol
      and [3H]flunitrazepam. Direct phosphorylation of the enzymes in the presence of
      ATP-gamma-32P and Mg2+, as well as Cl-/HCO3- sensitive dephosphorylation, is also
      associated with this 56 kDa peptide. Both preparations also showed one subunit
      with molecular mass 56 kDa that was immunoreactive with GABAAR beta3 subunit. The
      use of a fluorescent dye for Cl- demonstrated that HCO3-(27 mmol l-1) causes a
      twofold increase in Cl- influx into proteoliposomes containing reconstituted
      ATPases from MBNs, but HCO3- had no effect on the reconstituted enzyme from OSNs.
      These data are the first to demonstrate a differential effect of Cl- and HCO3- in
      the regulation of the Cl-/HCO3--ATPases functioning in neurons with different
      specializations.

PMID- 29218442
TI  - Silver nanoparticle conjugation affects antiacanthamoebic activities of
      amphotericin B, nystatin, and fluconazole.
AB  - Infectious diseases are the leading cause of morbidity and mortality, killing
      more than 15 million people worldwide. This is despite our advances in
      antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising
      technology to enhance drug efficacy and formation of effective vehicles for drug
      delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes),
      and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were
      synthesized successfully and characterized by ultraviolet-visible
      spectrophotometry, Fourier transform infrared spectroscopy, and atomic force
      microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba
      castellanii belonging to the T4 genotype using amoebicidal assay and host cell
      cytotoxicity assay. Viability assays revealed that silver nanoparticles
      conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited
      significant antiamoebic properties compared with drugs alone or AgNPs alone (P <
      0.05) as determined by Trypan blue exclusion assay. In contrast, conjugation of
      fluconazole with AgNPs had limited effect on its antiamoebic properties. Notably,
      AgNP-coated drugs inhibited amoebae-mediated host cell cytotoxicity as determined
      by measuring lactate dehydrogenase release. Overall, here we present the
      development of a new formulation of more effective antiamoebic agents based on
      AgNPs coated with drugs that hold promise for future applications.

PMID- 29218443
TI  - Prevalence and associated risk factors of Giardia duodenalis infection among
      school-going children in Nepal.
AB  - This study aimed to determine the prevalence of intestinal parasites and its
      associated risk factors among school-going children in Kathmandu, Nepal. Between
      August and September 2016, a total of 333 stool samples were collected from
      children at five public schools. The collected samples were subjected to formol
      ether concentration, followed by conventional microscopic examination for
      intestinal parasites. The overall prevalence of intestinal parasites was 24.3%
      (81/333), with Giardia spp. showing the highest prevalence of 18.9% (63/333).
      Samples positive for Giardia spp. by microscopy were further subjected to
      quantitative polymerase chain reaction (qPCR) for G. duodenalis, resulting in a
      positive ratio of 100%. The positive ratio of Giardia spp. was considerably high
      among children consuming tanker water (27.3%), jar water (21.0%), and tap water
      (17.5%). Our results demonstrated that G. duodenalis remains predominant in
      school-going children in Nepal.

PMID- 29218444
TI  - Resistance to apoptosis in Leishmania infantum-infected human macrophages: a
      critical role for anti-apoptotic Bcl-2 protein and cellular IAP1/2.
AB  - Apoptosis is essential for maintaining tissue homoeostasis in multi-cellular
      organisms, also occurring as a defence mechanism against a number of infectious
      agents, such as parasites. Among intracellular protozoan parasites reported to
      interfere with the apoptotic machinery of the host cell, Leishmania (L.) sp. have
      been described, although the various species might activate different pathways in
      their host cells. Since until now it is not yet well clarified the signalling
      pathway involved in the apoptosis modulation by L. infantum, the aim of this work
      was to investigate the role of the anti-apoptotic protein, Bcl-2, and the
      inhibitors of apoptosis IAP1/2 (cIAP1/2) in cell death resistance showed in L.
      infantum-infected human macrophages. We observed that actinomycin D-induced
      apoptosis in U-937 cells, evaluated by Annexin V-CY3, DNA fragmentation and
      caspase-3, caspase-8, caspase-9 activation assays, was inhibited in the presence
      of L. infantum promastigotes and that, in these conditions, Bcl-2 protein
      expression resulted significantly upregulated. Interestingly, L. infantum
      infection in combination with the Bcl-2 inhibitor, ABT-737, significantly
      increased the apoptotic process in actinomycin D-treated cells, suggesting a role
      for Bcl-2 in the anti-apoptotic regulation of human macrophages induced by L.
      infantum infection. Moreover, Western blotting analysis demonstrated not only a
      significantly upregulation of cIAP1/2 in infected U-937 cells, but also that the
      inhibition of cIAPs, employing specific siRNAs, restored the apoptotic effect of
      actinomycin in infected macrophages. These results clearly support the hypothesis
      that Bcl-2 and cIAPs are strongly involved in the anti-apoptotic action played by
      L. infantum in human macrophages.

PMID- 29218445
TI  - Demonstration of Nucleoside Transporter Activity in the Nose-to-Brain
      Distribution of [18F]Fluorothymidine Using PET Imaging.
AB  - To evaluate the role of nucleoside transporters in the nose-to-brain uptake of
      [18F]fluorothymidine (FLT), an equilibrative nucleoside transporter (ENT1,2) and
      concentrative nucleoside transporter (CNT1-3) substrate, using PET to measure
      local tissue concentrations. Anesthetized Sprague-Dawley rats were administered
      FLT by intranasal (IN) instillation or tail-vein injection (IV). NBMPR
      (nitrobenzylmercaptopurine riboside), an ENT1 inhibitor, was administered either
      IN or intraperitoneally (IP). Dynamic PET imaging was performed for up to 40 min.
      A CT was obtained for anatomical co-registration and attenuation correction. Time
      activity curves (TACs) were generated for the olfactory bulb (OB) and remaining
      brain, and the area-under-the-curve (AUC) for each TAC was calculated to
      determine the total tissue exposure of FLT. FLT concentrations were higher in the
      OB than in the rest of the brain following IN administration. IP administration
      of NBMPR resulted in increased OB and brain FLT exposure following both IN and IV
      administration, suggesting that NBMPR decreases the clearance rate of FLT from
      the brain. When FLT and NBMPR were co-administered IN, there was a decrease in
      the OB AUC while an increase in the brain AUC was observed. The decrease in OB
      exposure was likely the result of inhibition of ENT1 uptake activity in the nose
      to-brain transport pathway. FLT distribution patterns show that nucleoside
      transporters, including ENT1, play a key role in the distribution of transporter
      substrates between the nasal cavity and the brain via the OB.

PMID- 29218446
TI  - Cumulative pregnancy and live birth rates through assisted reproduction in women
      44-45 years of age: is there any hope?
AB  - PURPOSE: The purpose of the study is to calculate the cumulative pregnancy rate
      and cumulative live birth rate in women undergoing in vitro fertilization (IVF)
      at ages 44-45. METHODS: The study calculated cumulative live pregnancy rate and
      cumulative live birth rate of 124 women aged 44 to 45 years old who commenced IVF
      treatment. MAIN OUTCOME MEASURES: The main outcome measures are cumulative live
      pregnancy rate and cumulative live birth rate. RESULTS: Cumulative live pregnancy
      rates following 1, 2, 3, and 4 cycles were 5.6, 11, 17, and 20%, respectively,
      with no additional pregnancies in further cycles. Cumulative live birth rates
      following 1, 2, and 3 cycles were 1.6, 3, and 7%, respectively, with no
      additional live births in further cycles. CONCLUSIONS: The cumulative pregnancy
      rate rises during the first 4 cycles and cumulative live birth rate rises during
      the first 3 cycles, with no additional rise in pregnancies or deliveries
      thereafter, suggesting that it is futile to offer more than 3 cycles of treatment
      to 44-45-year-old women.

PMID- 29218447
TI  - Urban climate modifies tree growth in Berlin.
AB  - Climate, e.g., air temperature and precipitation, differs strongly between urban
      and peripheral areas, which causes diverse life conditions for trees. In order to
      compare tree growth, we sampled in total 252 small-leaved lime trees (Tilia
      cordata Mill) in the city of Berlin along a gradient from the city center to the
      surroundings. By means of increment cores, we are able to trace back their growth
      for the last 50 to 100 years. A general growth trend can be shown by comparing
      recent basal area growth with estimates from extrapolating a growth function that
      had been fitted with growth data from earlier years. Estimating a linear model,
      we show that air temperature and precipitation significantly influence tree
      growth within the last 20 years. Under consideration of housing density, the
      results reveal that higher air temperature and less precipitation led to higher
      growth rates in high-dense areas, but not in low-dense areas. In addition, our
      data reveal a significantly higher variance of the ring width index in areas with
      medium housing density compared to low housing density, but no temporal trend.
      Transferring the results to forest stands, climate change is expected to lead to
      higher tree growth rates.

PMID- 29218449
TI  - Generic calibration of a simple model of diurnal temperature variations for
      spatial analysis of accumulated degree-days.
AB  - Accumulated growing degree-days (aGDD) are widely used to predict phenological
      stages of plants and insects. It has been shown in the past that the best
      predictive performance is obtained when aGDD are computed from hourly temperature
      data. As the latter are not always available, models of diurnal temperature
      changes are often employed to retrieve the required information from data of
      daily minimum and maximum temperatures. In this study, we examine the performance
      of a well-known model of hourly temperature variations in the context of a
      spatial assessment of aGDD. Specifically, we examine whether a generic
      calibration of such a temperature model is sufficient to infer in a reliable way
      spatial patterns of key phenological stages across the complex territory of
      Switzerland. Temperature data of a relatively small number of meteorological
      stations is used to obtain a generic model parameterization, which is first
      compared with site-specific calibrations. We show that, at the local scale, the
      predictive skill of the generic model does not significantly differ from that of
      the site-specific models. We then show that for aGDD up to 800  degrees C d (on a
      base temperature of 10  degrees C), phenological dates predicted with aGDD
      obtained from estimated hourly temperature data are within +/- 3 days of dates
      estimated on the basis of observed hourly temperatures. This suggests the generic
      calibration of hourly temperature models is indeed a valid approach for pre
      processing temperature data in regional studies of insect and plant phenology.

PMID- 29218448
TI  - How does spa treatment affect cardiovascular function and vascular endothelium in
      patients with generalized osteoarthritis? A pilot study through plasma asymmetric
      di-methyl arginine (ADMA) and L-arginine/ADMA ratio.
AB  - The study aims to investigate the effect of spa treatment on vascular endothelium
      and clinical symptoms of generalized osteoarthritis. Forty generalized
      osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA
      patients followed on university hospital locomotor system disease ambulatory
      clinics were included as study and control groups, respectively. Study group
      received spa treatment including thermal water baths, physical therapy
      modalities, and exercises. Control group was followed with home exercises for 15
      days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6
      min walking test, including fingertip O2 saturation, systolic/diastolic blood
      pressure, and pulse rate, were measured at the beginning and at the end of
      treatment. Groups were evaluated with VAS pain, patient, and physician global
      assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of
      treatment. In study group, L-arginine and L-arginine/ADMA ratio showed
      statistically significant increase after treatment. Plasma ADMA levels did not
      change. There is no significant difference in intergroup comparison. Study group
      displayed statistically significant improvements in all clinical parameters. The
      study showed that spa treatment does not cause any harm to the vascular
      endothelium through ADMA. Significant increase in plasma L-arginine and L
      arginine/ADMA ratio suggests that balneotherapy may play a preventive role on
      cardiovascular diseases. Balneotherapy provides meaningful improvements on
      clinical parameters of GOA.

PMID- 29218450
TI  - Diagnosing and Correcting Mass Accuracy and Signal Intensity Error Due to Initial
      Ion Position Variations in a MALDI TOFMS.
AB  - Frustrated by worse than expected error for both peak area and time-of-flight
      (TOF) in matrix assisted laser desorption ionization (MALDI) experiments using
      samples prepared by electrospray deposition, it was finally determined that there
      was a correlation between sample location on the target plate and the measured
      TOF/peak area. Variations in both TOF and peak area were found to be due to small
      differences in the initial position of ions formed in the source region of the
      TOF mass spectrometer. These differences arise largely from misalignment of the
      instrument sample stage, with a smaller contribution arising from the non-ideal
      shape of the target plates used. By physically measuring the target plates used
      and comparing TOF data collected from three different instruments, an estimate of
      the magnitude and direction of the sample stage misalignment was determined for
      each of the instruments. A correction method was developed to correct the TOFs
      and peak areas obtained for a given combination of target plate and instrument.
      Two correction factors are determined, one by initially collecting spectra from
      each sample position used and another by using spectra from a single position for
      each set of samples on a target plate. For TOF and mass values, use of the
      correction factor reduced the error by a factor of 4, with the relative standard
      deviation (RSD) of the corrected masses being reduced to 12-24 ppm. For the peak
      areas, the RSD was reduced from 28% to 16% for samples deposited twice onto two
      target plates over two days. Graphical Abstract.

PMID- 29218451
TI  - The Trajectory from Mood to Obesity.
AB  - PURPOSE OF REVIEW: To describe and explain the relationships between mood
      disturbances and the development of obesity. RECENT FINDINGS: That depression,
      anxiety, PTSD, or severe stresses can promote obesity as a side-effect of the
      drugs used to treat them, or through "carbohydrate craving" to enhance brain
      serotonin synthesis and alleviate dysphoria by consuming foods that are rich in
      both carbohydrates and fats. That seasonal affective disorder and severe PMS can
      independently cause patients to overconsume foods rich in both carbohydrates and
      fats. The obesity caused by drugs or mood disorders associated with "carbohydrate
      craving" leading to excess calorie intake can be suppressed by dietary measures.

PMID- 29218452
TI  - Inhibition of the K+ conductance and Cole-Moore shift of the oncogenic Kv10.1
      channel by amiodarone.
AB  - The ectopic overexpression of the voltage-dependent Eag1 (Kv10.1) K+ channel is
      associated with the cancerous phenotype in about 70% of human cancers and tumor
      cell lines. Recent reports showed that, compared with the canonical Shaker
      related Kv family, Kv10.1 presents unique structural and functional properties.
      Herein, we report the interaction of the class III anti-arrhythmic compound
      amiodarone with Kv10.1. Using whole-cell patch clamp, we found that amiodarone
      inhibits Kv10.1 channel conductance with nanomolar affinity. Additionally, and
      interestingly, we also report that amiodarone inhibits the characteristic Cole
      Moore shift of Eag1 channels. Our observations are interpreted considering the
      structural-functional characteristics of these channels. We conclude that
      amiodarone possibly binds with high affinity to the voltage sensor module,
      altering the gating of Kv10.1.

PMID- 29218453
TI  - Energy depletion and not ROS formation is a crucial step of glucolipotoxicity
      (GLTx) in pancreatic beta cells.
AB  - We have shown previously that genetic or pharmacological deletion of KATP
      channels protect against beta cell dysfunction induced by reactive oxygen species
      (ROS). Since it is assumed that glucolipotoxicity (GLTx) causes ROS production,
      we aimed to evaluate whether suppression of KATP channel activity can also
      prevent beta cell damage evoked by GLTx. We used an in vitro model of GLTx and
      measured distinct parameters of stimulus-secretion coupling. GLTx gradually
      induced disturbances of Ca2+ oscillations over 3 days. This impairment in Ca2+
      dynamics was partially reversed in beta cells without functional KATP channels
      (SUR1-/-) and by the sulfonylurea gliclazide but not by tolbutamide. By contrast,
      the GLTx-induced suppression of glucose-induced insulin secretion could not be
      rescued by decreased KATP channel activity pointing to a direct interaction of
      GLTx with the secretory capacity. Accordingly, GLTx also suppressed KCl-induced
      insulin secretion. GLTx was not accompanied by decisively increased ROS
      production or enhanced apoptosis. Insulin content of beta cells was markedly
      reduced by GLTx, an effect not prevented by gliclazide. Since GLTx markedly
      diminished the mitochondrial membrane potential and cellular ATP content, lack of
      ATP is assumed to decrease insulin biosynthesis. The deleterious effect of GLTx
      is therefore caused by direct interference with the secretory capacity whereby
      reduction of insulin content is one important parameter. These findings deepen
      our understanding how GLTx damages beta cells and reveal that GLTx is
      disconnected from ROS formation, a notion important for targeting beta cells in
      the treatment of diabetes. Overall, GLTx-induced energy depletion may be a
      primary step in the cascade of events leading to loss of beta cell function in
      type-2 diabetes mellitus.

PMID- 29218454
TI  - The extraordinary AFD thermosensor of C. elegans.
AB  - The nematode C. elegans exhibits complex thermal experience-dependent navigation
      behaviors in response to environmental temperature changes of as little as 0.01
      degrees C over a > 10 degrees C temperature range. The remarkable thermosensory
      abilities of this animal are mediated primarily via the single pair of AFD
      sensory neurons in its head. In this review, we describe the contributions of AFD
      to thermosensory behaviors and temperature-dependent regulation of organismal
      physiology. We also discuss the mechanisms that enable this neuron type to adapt
      to recent temperature experience and to exhibit extraordinary thermosensitivity
      over a wide dynamic range.

PMID- 29218455
TI  - The primary cilium - once a "rudimentary" organelle that is now a ubiquitous
      sensory cellular structure involved in many pathological disorders.
AB  - This article looks mostly at the steps that have led to the primary cilium
      finding its place in our understanding of cell biology, developmental biology,
      and medical syndromes due to its aberrations. It is a personal account that
      stresses, if nothing else, the value of the adage "stick to your guns". My
      obsession with this organelle, following on from fascination with the centriole,
      has led to a whole career devoted to determining the nature and role of primary
      cilia in basic cell biology, which has proved much more important than had been
      appreciated for almost a century. They are heavily involved in very many aspects
      of cell physiology that have much wider implications with regard to human biology
      and probably throughout the animal kingdom. That aberrations, to the surprise of
      many researchers in their structure or functioning has led to their being
      implicated or perhaps deeply involved in an extraordinary range of medical
      conditions. This invitation allows me to raise crucial questions that need
      answers regarding the regulation of their genesis, their cache of both
      intracellular and extracellular signal, and their association with a multitude of
      development processes from embryo to adult status.

PMID- 29218456
TI  - Assessment of TANK-binding kinase 1 as a therapeutic target in cancer.
AB  - TANK-binding kinase 1 (TBK1) is central to multiple biological processes that
      promote tumorigenesis including cell division, autophagy, innate immune response
      and AKT-pro survival signaling. TBK1 is well studied and most known for its
      function in innate immunity. However, the serine threonine protein kinase
      received significant attention as a synthetic lethal partner and effector of the
      major oncogene, RAS. This review summarizes newly identified cancer promoting
      functions of TBK1 and evaluates the therapeutic potential of targeting TBK1 in
      cancer.

PMID- 29218457
TI  - Phenotypical change of tumor-associated macrophages in metastatic lesions of
      clear cell renal cell carcinoma.
AB  - Macrophages are the main immune cells of the tumor microenvironment in clear cell
      renal cell carcinoma (ccRCC). A high density of CD163+ or CD204+ tumor-associated
      macrophages (TAMs), rather than the density of total TAMs, is known to be linked
      to poor clinical outcome. In the present study, we investigated the phenotypical
      differences between the paired primary and metastatic lesions in ccRCC cases.
      Using immunostaining, the densities of CD163+ and CD204+ TAMs in metastatic
      lesions were found to be significantly lower compared to primary lesions,
      although the total number of TAMs was increased in metastatic lesions. Since
      CD163 and CD204 are considered to be the markers of an M2/protumor phenotype in
      macrophages, TAMs in metastatic lesions are suggested to have a greater
      M1/inflammatory function compared with those from primary lesions. These findings
      give new insights in regard to the immunological status of metastatic lesions of
      ccRCC.

PMID- 29218458
TI  - Evaluation of amyloid status in a cohort of elderly individuals with memory
      complaints: validation of the method of quantification and determination of
      positivity thresholds.
AB  - OBJECTIVE: Our aim is to validate the process steps implemented by the French
      CATI platform to assess amyloid status, obtained from 18F-Florbetapir PET scans,
      in a cohort of 318 cognitively normal subjects participating in the INSIGHT-preAD
      study. Our objective was to develop a method with partial volume effect
      correction (PVEC) on untransformed PET images, using an automated pipeline
      ("RACHEL") adapted to large series of patients and including quality checks of
      results. METHODS: We compared RACHEL using different options (with and without
      PVEC, different sets of regions of interest), to two other methods validated in
      the literature, referred as the "AVID" and "CAEN" methods. A standard uptake
      value ratio (SUVR) was obtained with the different methods for participants to
      another French study, IMAP, including 26 normal elderly controls (NEC), 11
      patients with mild cognitive impairment (MCI) and 16 patients with Alzheimer's
      disease (AD). We determined two cutoffs for RACHEL method by linear correlation
      with the other methods and applied them to the INSIGHT-preAD subjects. RESULTS:
      RACHEL including PVEC and a combination of the whole cerebellum and the pons as a
      reference region allowed the best discrimination between NEC and AD participants.
      A strong linear correlation was found between RACHEL and the other two methods
      and yielded the two cutoffs of 0.79 and 0.88. According to the more conservative
      threshold, 19.8% of the INSIGHT-preAD subjects would be considered amyloid
      positive, and 27.7% according to the more liberal threshold. CONCLUSIONS: With
      our method, we clearly discriminated between NEC with negative amyloid status and
      patients with clinical AD. Using a linear correlation with other validated
      cutoffs, we could infer our own positivity thresholds and apply them to an
      independent population. This method might be useful to the community, especially
      when the optimal cutoff could not be obtained from a population of healthy young
      adults or from correlation with post-mortem results.

PMID- 29218459
TI  - Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary
      disease: a prospective study.
AB  - PURPOSE: Measuring IGF-1, a biomarker for GH activity, is critical to evaluating
      disordered hypothalamic-pituitary GH axis. Inconsistent IGF-1 measurements among
      different immunoassays are well documented. We switched from Immulite 2000
      immunoassay to narrow-mass-extraction, high-resolution liquid chromatography mass
      spectrometry (LC-MS) compliant with recent consensus recommendations on assay
      standardization. Comparability of these two assays in patients with pituitary
      disease in a clinical practice setting is not known. We sought to compare IGF-1
      levels on Immulite 2000 and LC-MS in samples from naive and treated patients with
      secretory and non-secretory pituitary masses. METHODS: We prospectively collected
      serum samples from 101 patients treated at the Cedars-Sinai Pituitary Center
      between February 2012 and March 2014. We intentionally recruited more patients
      with acromegaly or GH deficiency to ensure a clinically representative cohort.
      Samples were classified as in or out of the respective reference ranges. Bland
      Altman analysis was used to assess agreement between assays. RESULTS: Twenty-four
      percent of samples were classified differently as below, in, or above range.
      Agreement between the assays was poor overall, with a significant bias for
      immunoassay reporting higher values than LC-MS. This pattern was also observed in
      patients with acromegaly and those with >= 2 pituitary hormone deficiencies.
      CONCLUSIONS: IGF-1 results may differ after switching from an older immunoassay
      to a consensus-compliant assay such as LC-MS. Clinicians should consider the
      potential impact of assay switching before altering treatment due to discrepant
      results, particularly in patients monitored over time, such as those with
      acromegaly and GH deficiency.

PMID- 29218460
TI  - A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation
      to Aid Glaucoma Diagnosis.
AB  - This paper proposes a novel Adaptive Region-based Edge Smoothing Model (ARESM)
      for automatic boundary detection of optic disc and cup to aid automatic glaucoma
      diagnosis. The novelty of our approach consists of two aspects: 1) automatic
      detection of initial optimum object boundary based on a Region Classification
      Model (RCM) in a pixel-level multidimensional feature space; 2) an Adaptive Edge
      Smoothing Update model (AESU) of contour points (e.g. misclassified or irregular
      points) based on iterative force field calculations with contours obtained from
      the RCM by minimising energy function (an approach that does not require
      predefined geometric templates to guide auto-segmentation). Such an approach
      provides robustness in capturing a range of variations and shapes. We have
      conducted a comprehensive comparison between our approach and the state-of-the
      art existing deformable models and validated it with publicly available datasets.
      The experimental evaluation shows that the proposed approach significantly
      outperforms existing methods. The generality of the proposed approach will enable
      segmentation and detection of other object boundaries and provide added value in
      the field of medical image processing and analysis.

PMID- 29218461
TI  - Triphasic mitral inflow pattern associated with hemodynamic deterioration in
      anemia or mitral regurgitation: a report of two cases.
AB  - We present two cases with a mid-diastolic mitral inflow peak called an "L wave"
      due to underlying diseases. Case 1 was an 81-year-old woman with severe anemia
      (hemoglobin level of 3.9 g/dL). Pulsed Doppler echocardiography showed an L wave
      that disappeared after transfusion of red cell concentrates. Case 2 was a 72-year
      old woman with severe mitral regurgitation due to ruptured chordae tendineae.
      Pulsed Doppler echocardiography showed an L wave that disappeared after mitral
      valve repair. The present report suggests that both severe anemia and mitral
      regurgitation might have contributed to L wave formation, which suggests
      hemodynamic deterioration.

PMID- 29218462
TI  - A single institution experience with palbociclib toxicity requiring dose
      modifications.
AB  - PURPOSE: Since the widespread implementation of adding palbociclib to endocrine
      therapy in clinical practice, myelosuppression is becoming increasingly
      recognized as a toxicity that may lead to dose modification. We aimed to
      characterize toxicities observed with palbociclib resulting in dose modifications
      and prescriber preferences in modifying palbociclib dosage in response to
      treatment-related toxicities outside the context of a clinical trial. METHODS: We
      conducted a single institution, retrospective study of treatment-related adverse
      events (AEs) resulting in modifications in dose and schedule and the methods by
      which dose modifications occurred in patients with advanced hormone receptor (HR)
      positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer
      receiving palbociclib and endocrine therapy. RESULTS: From 2/2015 to 10/2016, 100
      patients were identified for inclusion in this study. Treatment with palbociclib
      and endocrine therapy resulted in dose modifications in 38.0% of patients due to
      AEs with 18.4% requiring subsequent dose changes. Most palbociclib dose
      modifications occurred during the first 2 cycles. Grade 3-4 neutropenia accounted
      for 54.8% events of palbociclib dose modification. Most providers (65.8%) dose
      reduced palbociclib from 125 mg to 100 mg as their preferred method of dose
      modification, while others dose reduced from 125 mg to 75 mg (10.5%) and altered
      the schedule to 125 mg every other day (7.9%). A comparable rate of palbociclib
      dose modifications and subsequent dose changes were identified in an age >= 65
      subgroup. In this group, dose adjustments were most commonly from grade 3-4
      neutropenia, occurred mainly during cycle 1, and were most frequently addressed
      by dose reduction from 125 to 100 mg. CONCLUSIONS: Neutropenia remains the
      predominant cause for palbociclib dose modification and most modifications occur
      within the first two cycles. Older age (>= 65) does not affect palbociclib
      tolerance. Our findings provide context outside of a clinical trial that inform
      ongoing studies evaluating the safety and feasibility of palbociclib-based
      therapies.

PMID- 29218464
TI  - Microalgae Lipid Staining with Fluorescent BODIPY Dye.
AB  - The staining of lipids in algae cells with BODIPY dyes is much less studied
      compared to Nile red; therefore, a complex of issues concerning staining details
      and fluorescence measurements still should be clarified for the species that vary
      in cell wall complexity. Nevertheless, some general guidelines could be given,
      and a preliminary protocol of the method is provided based on the existing data.
      The semiquantification of lipid could be reliable if the staining protocol will
      be developed and adapted for particular microalgae species.

PMID- 29218463
TI  - One-two punch mechanism of gene repression: a fresh perspective on gene
      regulation.
AB  - Cellular differentiation depends on temporally controlled waves of gene
      activation and inactivation that ultimately transform one cell type into another.
      It is well established that transcription factor cascades coordinate the timely
      activation of gene expression clusters during development. In comparison, much
      less is understood about how gene repression events are coordinated with the
      transcription factor-driven waves of gene activation and how this repression is
      achieved at a mechanistic level. Using budding yeast as a model, we recently
      discovered a new gene regulatory event, whereby a central meiotic transcription
      factor induces the expression of an mRNA isoform to repress gene expression
      through an integrated transcriptional and translational mechanism. This new model
      could explain how gene activation and inactivation waves can be temporally
      coordinated. In this review, we discuss our findings and their potential
      implications.

PMID- 29218465
TI  - Long-Term Survival of Recurrent Intrahepatic Cholangiocarcinoma: The Impact and
      Selection of Repeat Surgery.
AB  - BACKGROUND: Definitive guidelines for recurrent intrahepatic cholangiocarcinoma
      (ICC) do not exist. This study has focused on the repeat surgery when analyzing
      the survival outcomes of recurrent ICC. We evaluated the relationship between
      clinicopathological features of the primary tumor and implementation of the
      repeat surgery to identify its potential selection criteria. METHODS: A total of
      108 patients with recurrent ICC between 1993 and 2015 were analyzed. Of these, 15
      patients underwent repeat surgery and 93 did not. RESULTS: Seven out of 29
      patients with intrahepatic recurrence and eight out of 44 patients with
      extrahepatic recurrence were amenable to the repeat surgery. Thirty-five patients
      with simultaneous or consequent intrahepatic recurrence and extrahepatic
      recurrence were not amenable to the repeat surgery. Patients who underwent repeat
      surgery had a lower proportion of lymph node metastases (n = 0 [0%] vs. n = 47
      [50.5%], p < 0.001), multiple tumors in the primary tumor (n = 1 [6.7%] vs. n =
      31 [33.3%], p = 0.037), or early recurrence (<= 1 year; n = 4 [26.7%] vs. n = 62
      [66.7%], p = 0.003). Survival after recurrence (SAR) was better in patients who
      underwent repeat surgery than in those who did not (median SAR time: 91.6 vs.
      10.4 months, and 3-year survival: 86.7 vs. 8.7%, respectively, p < 0.001).
      CONCLUSIONS: Repeat surgery for recurrent ICC with an appropriate selection can
      be associated with prolonged survival. Regarding the feasibility, nodal status,
      number of tumors on the primary tumor, and time to recurrence may be considered
      as selection criteria.

PMID- 29218466
TI  - Acute herpes zoster and post herpetic neuralgia in primary care: a study of
      diagnosis, treatment and cost.
AB  - Acute herpes zoster and its complication post herpetic neuralgia represent a
      significant challenge to primary care physicians in their care of an ageing
      population of patients. This was a cross-sectional observational study by means
      of a quantitative survey of 1,000 general practitioners registered in Ireland
      exploring the frequency of diagnosis, methods of treatment and cost of AHZ and
      PHN in primary care. We recorded an 18% response rate (n = 184) with an 83%
      completion rate (n = 152/184). 80% of cases of AHZ occurred in patients aged 50
      years or more with 81% of study participants encountering cases at a rate of 1-3
      patients per month. Famciclovir (37%) and valaciclovir (36%) were the most
      commonly prescribed antiviral agents. Mild opioids (32%) were the most common
      analgesic agents used for first line AHZ pain, and pregabalin (37%) the most
      commonly prescribed analgesic agent for second line AHZ pain. Pregabalin was also
      the most commonly prescribed analgesic for both first and second line PHN pain
      (29% and 24%, respectively). The mean per-case direct cost (medication and GP
      visits) of treating AHZ and PHN in primary care was ?195 (range ?153-?236) and
      ?201 (range ?140-?313), respectively. Based on national sentinel data the
      estimated annual direct costs of treating AHZ and PHN in primary care is
      ?2,278,196 (range ?1,793,399-?2, 763,445). The treatment of AHZ and PHN
      represents both a significant care and cost burden on primary care resources in
      Ireland in keeping with other European based studies.

PMID- 29218467
TI  - Antibiotic prescription and clinical management of common infections among
      general practitioners in Latvia, Lithuania, and Sweden: a pilot survey with a
      simple protocol.
AB  - Comparative information on diagnosis-related antibiotic prescribing patterns are
      scarce from primary care within and between countries. To describe and compare
      antibiotic prescription and routine management of infections in primary care in
      Latvia (LV), Lithuania (LT) and two study sites in Sweden (SE), a cross-sectional
      observational study on patients who consulted due to sypmtoms compatible with
      infection was undetraken. Infection and treatment was detected and recorded by
      physicians only. Data was collected from altogether 8786 consecutive patients
      with infections in the three countries. Although the overall proportion of
      patients receiving an antibiotic prescription was similar in all three countries
      (LV and LT 42%, SE 38%), there were differences in the rate of prescription
      between the countries depending on the respective diagnoses. While penicillins
      dominated among prescriptions (LV 58%, LT 67%, SE 70%), phenoxymethylpenicillin
      was most commonly prescribed in Sweden (57% of all penicillins), while it was
      amoxicillin with or without clavulanic acid in Latvia (99%) and Lithuania (85%)
      respectively. Pivmecillinam and flucloxacillin, which accounted for 29% of
      penicillins in Sweden, were available neither in Latvia nor in Lithuania. The
      applied methodology was simple, and provided useful information on differences in
      treatment of common infections in ambulatory care in the absence of available
      computerized diagnosis-prescription data. Despite some limitations, the method
      can be used for assessment of intention to treat and compliance to treatment
      guidelines and benchmarking locally, nationally, or internationally, just as the
      point prevalence surveys (PPS) protocols have been used in hospitals all over
      Europe.

PMID- 29218468
TI  - Prediction of unfavorable outcomes in cryptococcal meningitis: results of the
      multicenter Infectious Diseases International Research Initiative (ID-IRI)
      cryptococcal meningitis study.
AB  - Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients,
      particularly human immunodeficiency virus (HIV)-positive patients, but CM may
      also occur in apparently immunocompetent individuals. Outcome analyses have been
      performed in such patients but, due to the high prevalence of HIV infection
      worldwide, CM patients today may be admitted to hospitals with unknown HIV
      status, particularly in underdeveloped countries. The objective of this
      multicenter study was to analyze all types of CM cases in an aggregate cohort to
      disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM
      patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics,
      clinical, microbiological, radiological, therapeutic data, and outcomes were
      included. Death, neurological sequelae, or relapse were unfavorable outcomes.
      Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104
      (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale
      (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p =
      0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable
      outcomes. On the other hand, malignancy (p = 0.026) was associated with poor
      outcomes. Although all CM patients require prompt and rational fungal management,
      those with significant risks for poor outcomes need to be closely monitored.

PMID- 29218469
TI  - Discrimination of Schisandrae Chinensis Fructus and Schisandrae Sphenantherae
      Fructus based on fingerprint profiles of hydrophilic components by high
      performance liquid chromatography with ultraviolet detection.
AB  - High-performance liquid chromatography with ultraviolet detection (HPLC-UV) using
      20 mM phosphate mobile phase and an octadecylsilyl column (Triart C18, 150 * 3.0
      mm i.d., 3 MUm) has been developed for the analysis of hydrophilic compounds in
      the water extract of Schisandrae Fructus samples. The present HPLC-UV method
      permits the accurate and precise determination of malic, citric, and
      protocatechuic acids in the Japanese Pharmacopoeia (JP) Schisandrae Fructus,
      Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus. The JP
      Schisandrae Fructus studied contains 27.98 mg/g malic, 107.08 mg/g citric, and
      0.42 mg/g protocatechuic acids, with a relative standard deviation (RSD) of
      repeatability of <0.9% (n = 6). The content of malic acids in Schisandrae
      Chinensis Fructus is approximately ten times that in Schisandrae Sphenantherae
      Fructus. To examine whether the HPLC-UV method is applicable to the fingerprint
      based discrimination of Schisandrae Fructus samples obtained from Chinese
      markets, principal component analysis (PCA) was performed using the determined
      contents of organic acids and the ratio of six characteristic unknown peaks
      derived from hydrophilic components to internal standard peak areas. On the score
      plots, Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus
      samples are clearly discriminated. Therefore, the HPLC-UV method for the analysis
      of hydrophilic components coupled with PCA has been shown to be practical and
      useful in the quality control of Schisandrae Fructus.

PMID- 29218470
TI  - The Maximal Oxygen Uptake Verification Phase: a Light at the End of the Tunnel?
AB  - Commonly performed during an incremental test to exhaustion, maximal oxygen
      uptake (VO2max) assessment has become a recurring practice in clinical and
      experimental settings. To validate the test, several criteria were proposed. In
      this context, the plateau in oxygen uptake (VO2) is inconsistent in its
      frequency, reducing its usefulness as a robust method to determine "true" VO2max.
      Moreover, secondary criteria previously suggested, such as expiratory exchange
      ratios or percentages of maximal heart rate, are highly dependent on protocol
      design and often are achieved at VO2 percentages well below VO2max. Thus, an
      alternative method termed verification phase was proposed. Currently, it is clear
      that the verification phase can be a practical and sensitive method to confirm
      VO2max; however, procedures to conduct it are not standardized across the
      literature and no previous research tried to summarize how it has been employed.
      Therefore, in this review the knowledge on the verification phase was updated,
      while suggestions on how it can be performed (e.g. intensity, duration, recovery)
      were provided according to population and protocol design. Future studies should
      focus to identify a verification protocol feasible for different populations and
      to compare square-wave and multistage verification phases. Additionally, studies
      assessing verification phases in different patient populations are still
      warranted.

PMID- 29218471
TI  - Rural environment study for water from different sources in cluster of villages
      in Mehsana district of Gujarat.
AB  - Water pollution and water scarcity are major environmental issues in rural and
      urban areas. They lead to decline in the quality of water, especially drinking
      water. Proper qualitative assessment of water is thus necessary to ensure that
      the water consumed is potable. This study aims to analyze the physicochemical
      parameters in different sources of water in rural areas and assess the quality of
      water through a classification system based on BIS and CPCB standards. The
      classification method has defined water quality in six categories, viz., A, B, C,
      D, E, and F depending on the levels of physicochemical parameters in the water
      samples. The proposed classification system was applied to nine villages in Kadi
      Taluka, Mehsana district of Gujarat. The water samples were collected from
      borewells, lakes, Narmada Canal, and sewerage systems and were analyzed as per
      APHA and IS methods. It was observed that most of the physicochemical parameters
      of Narmada Canal and borewell water fell under class A, thus making them most
      suitable for drinking. Further, a health camp conducted at Karannagar village,
      Mehsana revealed no incidents of any waterborne diseases. However, there were
      certain incidents of kidney stones and joint pain in few villages due to high
      levels of TDS. Toxic metal analysis in all the water sources revealed low to
      undetectable concentration of toxic metals such as lead, arsenic, mercury, and
      cadmium in all the water sources. It is also recommended that the regular
      treatment of the Narmada Canal water be continued to maintain its excellent
      quality.

PMID- 29218472
TI  - Correction to: Quantifying and understanding carbon storage and sequestration
      within the Eastern Arc Mountains of Tanzania, a tropical biodiversity hotspot.
AB  - Upon publication of the original article [1], the authors noticed that the figure
      labelling for Fig. 4 in the online version was processed wrong. The top left
      panel should be panel a, with the panels to its right being b and c. d and e
      should be the panels on the lower row, and f is correct. The graphs themselves
      are all correct. It is simply the letter labels that are wrong.

PMID- 29218473
TI  - The Bidirectional, Absorbable, No-Drain Abdominoplasty.
AB  - This article outlines the author's technique, and the concepts of Bidirectional,
      Absorbable, No-Drain Abdominoplasty (BAND-Abdominoplasty). The attendant
      advantages and disadvantages are reviewed in the context of a retrospective, 5
      year, single surgeon series. 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- 29218474
TI  - Superomedial Pedicle Vertical Scar Breast Reduction: Objective and Subjective
      Assessment of Breast Symmetry and Aesthetics.
AB  - BACKGROUND: The superomedial vertical scar breast reduction (SVBR) described by
      Hall-Findlay is gaining popularity among surgeons worldwide. The aim of this
      study was to evaluate its long-term aesthetic outcome, the extent of quality of
      life improvement and the factors that influence patient satisfaction and
      reviewers' evaluation of aesthetic/surgical outcome. METHODS: In this historical
      prospective study, we included women who underwent SVBR at least one year prior
      to enrollment and responded to a quality of life questionnaire. Their breasts
      were photographed, measured and evaluated by the plastic surgery staff. RESULTS:
      A total of 40 patients responded to the questionnaire, and the breasts of 31 of
      them were measured and photographed. All 31 patients had good breast symmetry
      according to objective breast measurements. There was a clear correlation between
      the patients' and the reviewers' scores of breast symmetry, scar appearance and
      breast shape (r = 0.4-0.65, r = 0.432-0.495 and r = 0.335-0.403, respectively).
      The factor that most influenced reviewers' and patients' satisfaction with the
      overall aesthetic outcome was the breast-to-body proportion. CONCLUSIONS: The
      proportions between the breast size and the patient's body habitus are pivotal to
      patient satisfaction and should be taken into consideration when planning a
      reduction mammaplasty. The SVBR technique for breast reduction provided good
      cosmetic outcome and symmetry over a long-term follow-up. 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- 29218475
TI  - Transdermal Patch of Glyceryl Trinitrate to Enhance Survival of Random Pattern
      Skin Flaps.

PMID- 29218476
TI  - Google Trends as a Resource for Informing Plastic Surgery Marketing Decisions.
AB  - BACKGROUND: Celebrities have long influenced the medical decisions of the general
      population. By analyzing Google search data using Google Trends, we measured the
      impact of highly publicized plastic surgery-related events on the interest level
      of the general population in specific search terms. Additionally, we investigated
      seasonal and geographic trends around interest in rhinoplasties, which is
      information that physicians and small surgical centers can use to optimize
      marketing decisions. METHODS: Google Trends was used to access search data
      histories for three separate areas of interest: Kylie Jenner and lip fillers,
      Joan Rivers and plastic surgery, and rhinoplasty, which were then analyzed using
      two-tailed, two-sample equal variance t-tests. RESULTS: The average interest
      level in fillers increased by 30.31 points after Kylie Jenner announced that she
      received Juvederm lip injections. The interest level in plastic surgery was
      decreased by 21.3% the month after Joan Rivers' death. Between January 2004 and
      May 2017, the average interest level for rhinoplasty was significantly different
      in January/December (67.91 +/- 20.68) and June/July (70.12 +/- 18.89) from the
      remaining calendar months (63.58 +/- 19.67). Los Angeles, New York City, and
      Miami showed consistently high interest levels throughout the time period, while
      Tulsa, OK, showed a major interest increase between 2015 to 2016 of 65 points.
      CONCLUSIONS: A noticeable impact was observed in both celebrity cases on search
      term volume, and a seasonal effect is apparent for rhinoplasty searches. As many
      surgeons already employ aggressive Internet marketing strategies, understanding
      and utilizing these trends could help optimize their investments, increase social
      engagement, and increase practice awareness by potential patients. LEVEL OF
      EVIDENCE V: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 29218477
TI  - Safety and Efficacy of Facial Fat Grafting Under Local Anesthesia.
AB  - BACKGROUND: Facial fat grafting under local anesthesia has been widely performed
      in outpatient departments and private settings in China. The present study aimed
      to evaluate the safety and efficacy of facial fat grafting under local
      anesthesia. METHOD: A retrospective study was conducted on 155 patients who
      underwent facial fat grafting. The clinical data were recorded. Preoperative and
      postoperative two-dimensional images were acquired to evaluate the effect of
      facial fat grafting on refining facial contouring, rejuvenation as well as
      deformity reconstruction. The complications were recorded to assess the safety of
      the approach. RESULT: All the facial fat grafting procedures were performed
      successfully under local anesthesia. A majority of the patients who underwent one
      or more sessions of facial fat grafting under local anesthesia were satisfied
      with the cosmetic results. No severe complications occurred in these patients.
      CONCLUSIONS: In the present study, remarkable and natural improvements of facial
      contouring, rejuvenation as well as deformity reconstruction were achieved with
      facial fat grafting in most patients. Thus, the procedures performed under local
      anesthesia by experienced surgeons are safe. 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- 29218478
TI  - The Rejuvenating Effect and Tolerability of an Auto-Cross-Linked Hyaluronic Acid
      on Decolletage: A Pilot Prospective Study.
AB  - BACKGROUND: A novel auto-cross-linked hyaluronic acid formulation (HA-ACP) has
      been proposed as a treatment for skin rejuvenation. This prospective pilot study
      aims to assess its tolerability and performance in the treatment of skin aging of
      the decolletage. METHODS: Fifteen women (mean age 49.0 +/- 8.0  (range 30-65))
      who complained about the appearance of their decolletage were prospectively
      enrolled and treated with three sets of HA-ACP (IAL-SYSTEM ACP(r)) intradermal
      injections, administered three weeks apart. Control visits followed at 80 and 120
      days from enrollment. The rejuvenating effect was assessed using the Beagley
      Gibson and Fabi-Bolton scores. The investigators and the subjects also
      subjectively assessed skin appearance using a 1-10 scale. The rejuvenating effect
      and its persistence were assessed comparing the scores collected at the different
      experimental times by means of Wilcoxon rank tests. Adverse events and their
      duration were recorded and compared to those reported in the literature. RESULTS:
      The HA-ACP formulation provided a significant improvement according to the
      Beagley-Gibson score (p < 0.005) at all time points. At the 120-day follow-up,
      the Fabi-Bolton score was significantly improved with respect to baseline (p <
      0.05). The rejuvenating effect persisted unaltered between the 80-day and the 120
      day visits. At the 120-day visit, the subjects' and investigators' subjective
      scores were between 8 and 10 in most cases. No unexpected adverse effects were
      observed. All adverse effects were well tolerated and disappeared over a short
      period. CONCLUSIONS: The HA-ACP treatment under investigation is safe, well
      tolerated, and provides effective and long-lasting decolletage rejuvenation.
      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- 29218479
TI  - Robert M. Oneal and Lauralee A. Lutz: Leaders in Plastic Surgery (The Dingman
      Grabb Era 1946-1986).

PMID- 29218480
TI  - Discussion: Augmentation mastopexy with a dermal encapsulated round or anatomic
      autoprosthesis.

PMID- 29218482
TI  - A novel muscle-sparing high thoracotomy for upper thoracic spine resection and
      reconstruction.
AB  - PURPOSE: High thoracotomy allows access to the anterior cervicothoracic and upper
      thoracic vertebrae; however, traditional techniques transect shoulder girdle
      muscles, leading to postoperative shoulder dysfunction. Muscle-sparing techniques
      diminish this concern, but often sacrifice the quality of exposure. We describe a
      novel muscle-sparing, high thoracotomy approach for the treatment of ventral
      cervicothoracic and upper thoracic spine lesions. METHODS: A novel muscle
      sparing, high thoracotomy approach is described, utilizing a midline posterior
      incision with lateral extension from the lateral decubitus position. Five
      patients are presented to illustrate the application of this technique in
      thoracic tumors with intimate spinal involvement. RESULTS: The muscle-sparing,
      high thoracotomy approach afforded gross total resection and spinal
      reconstruction in five consecutive patients, including stage IV lung carcinoma
      with invasion of the T5 and T6 vertebral bodies, two malignant fibrous
      histiocytomas causing thoracic cord compression, a metastatic T6 lesion of
      unknown primary with associated cord compression; and a Pancoast tumor. All
      patients seen at 6 months had full symmetric shoulder range of motion
      postoperatively. CONCLUSIONS: The described muscle-sparing, high thoracotomy
      approach provides excellent exposure of the ventral cervicothoracic and upper
      thoracic spine without the morbidity associated with the transection of shoulder
      girdle muscle bellies. This technique is particularly useful in patients with
      primary malignant bone tumors requiring en bloc excision and metastatic tumors
      with large soft tissue components.

PMID- 29218481
TI  - Concepts for a therapeutic prolongation of nephrogenesis in preterm and low-birth
      weight babies must correspond to structural-functional properties in the
      nephrogenic zone.
AB  - Numerous investigations are dealing with anlage of the mammalian kidney and
      primary development of nephrons. However, only few information is available about
      the last steps in kidney development leading at birth to a downregulation of
      morphogen activity in the nephrogenic zone and to a loss of stem cell niches
      aligned beyond the organ capsule. Surprisingly, these natural changes in the
      developmental program display similarities to processes occurring in the kidneys
      of preterm and low-birth-weight babies. Although those babies are born at a time
      with a principally intact nephrogenic zone and active niches, a high proportion
      of them suffers on impairment of nephrogenesis resulting in oligonephropathy,
      formation of atypical glomeruli, and immaturity of parenchyma. The setting points
      out that up to date not identified noxae in the nephrogenic zone hamper primary
      steps of parenchyma development. In this situation, a possible therapeutic aim is
      to prolong nephrogenesis by medications. However, actual data provide information
      that administration of drugs is problematic due to an unexpectedly complex
      microanatomy of the nephrogenic zone, in niches so far not considered textured
      extracellular matrix and peculiar contacts between mesenchymal cell projections
      and epithelial stem cells via tunneling nanotubes. Thus, it remains to be figured
      out whether disturbance of morphogen signaling altered synthesis of extracellular
      matrix, disturbed cell-to-cell contacts, or modified interstitial fluid impair
      nephrogenic activity. Due to most unanswered questions, search for eligible drugs
      prolonging nephrogenesis and their reliable administration is a special challenge
      for the future.

PMID- 29218483
TI  - Asymmetrical trunk movement during walking improved to normal range at 3 months
      after corrective posterior spinal fusion in adolescent idiopathic scoliosis.
AB  - PURPOSE: To investigate the effects of posterior spinal fusion (PSF) and curve
      type on upper body movements in Adolescent Idiopathic Scoliosis (AIS) patients
      during gait. METHODS: Twenty-four girls (12-18 years) with AIS underwent PSF. 3D
      Gait-analyses were performed preoperatively, at 3 months and 1 year
      postoperatively. Mean position (0 degrees  represents symmetry) and range of
      motion (ROM) of the trunk (thorax-relative-to-pelvis) in all planes were
      assessed. Lower body kinematics and spatiotemporal parameters were also
      evaluated. RESULTS: Mean trunk position improved from 7.0 degrees  to 2.9 degrees
      in transversal plane and from 5.0 degrees  to - 0.8 degrees  in frontal plane at
      3 months postoperative (p < 0.001), and was maintained at 1 year. Trunk ROM in
      transverse plane decreased from 9.6 degrees  to 7.5 degrees  (p < 0.001) after
      surgery. No effects of PSF were observed on the lower body kinematics during the
      gait cycle. Patients with a double curve had a more axial rotated trunk before
      and after surgery (p = 0.013). CONCLUSION: In AIS patients, during gait an
      evident asymmetrical position of the trunk improved to an almost symmetric
      situation already 3 months after PSF and was maintained at 1 year. Despite a
      reduction of trunk ROM, patients were able to maintain the same walking pattern
      in the lower extremities after surgery. This improvement of symmetry and
      maintenance of normal gait can explain the rapid recovery and well functioning in
      daily life of AIS patients, despite undergoing a fusion of large parts of their
      spine.

PMID- 29218484
TI  - A Prospective Multicenter Study of a Fully Covered Metal Stent in Patients with
      Distal Malignant Biliary Obstruction: WATCH-2 Study.
AB  - BACKGROUND: Both fully covered (FC) and partially covered (PC) self-expandable
      metal stents (SEMSs) are now commercially available for distal malignant biliary
      obstruction (MBO). While FCSEMS can be easily removed at the time of re
      interventions, it is theoretically prone to migration. However, few comparative
      data between FC and PC SEMSs have been reported. AIMS: The aim of this study was
      to compare clinical outcomes of FCSEMS with those of PCSEMS. METHODS: This was a
      multicenter, prospective study of FCSEMS for unresectable distal MBO with a
      historical control of PCSEMS, which was previously reported as the WATCH study.
      The primary outcome was recurrent biliary obstruction (RBO), and secondary
      outcomes were stent migration, stent removal, stent-related adverse events, and
      survival. RESULTS: A total of 151 cases with unresectable distal MBO undergoing
      FCSEMS placement were enrolled and compared with a historical cohort of 141 cases
      undergoing PCSEMS placement. No significant differences were found in the rate of
      RBO (29 vs. 33%; P = 0.451), time to RBO (318 vs. 373 days; P = 0.382), and
      survival (229 vs. 196 days; P = 0.177) between FCSEMS and PCSEMS. The rate of
      stent migration also did not differ significantly between the two groups (14 vs.
      8%; P = 0.113). The removal of FCSEMSs was successful in all 24 attempted cases
      (100%). CONCLUSIONS: FCSEMSs appeared comparable to PCSEMSs in terms of RBO
      without a significant increase in stent migration rate in patients with
      unresectable distal MBO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000007131.

PMID- 29218486
TI  - Interaction study between HCV NS5A-D2 and NS5B using 19F NMR.
AB  - The non structural protein 5A (NS5A) regulates the replication of the hepatitis C
      viral RNA through a direct molecular interaction of its domain 2 (NS5A-D2) with
      the RNA dependent RNA polymerase NS5B. Because of conflicting data in the
      literature, we study here this molecular interaction using fluorinated versions
      of the NS5A-D2 protein derived from the JFH1 Hepatitis C Virus strain. Two
      methods to prepare fluorine-labelled NS5A-D2 involving the biosynthetic
      incorporation of a 19F-tryptophan using 5-fluoroindole and the posttranslational
      introduction of fluorine by chemical conjugation of 2-iodo-N
      (trifluoromethyl)acetamide with the NS5A-D2 cysteine side chains are presented.
      The dissociation constants (KD) between NS5A-D2 and NS5B obtained with these two
      methods are in good agreement, and yield values comparable to those derived
      previously from a surface plasmon resonance study. We compare benefits and
      limitations of both labeling methods to study the interaction between an
      intrinsically disordered protein and a large molecular target by 19F NMR.

PMID- 29218485
TI  - Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion
      Disease.
AB  - OBJECTIVES: Microvillus inclusion disease (MVID) is a severe form of neonatal
      diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B
      causes depolarization of enterocytes in the small intestine, which gives rise to
      chronic, unremitting secretory diarrhea. While the pathology of the small
      intestine in MVID patients is well described, little is known about
      extraintestinal effects of MYO5B mutation. METHODS: We examined stomach, liver,
      pancreas, colon, and kidney in Navajo MVID patients, who share a single
      homozygous MYO5B-P660L (1979C>T p.Pro660Leu, exon 16). Sections were stained for
      markers of the apical membrane to assess polarized trafficking. RESULTS: Navajo
      MVID patients showed notable changes in H/K-ATPase-containing tubulovesicle
      structure in the stomach parietal cells. Colonic mucosa was morphologically
      normal, but did show losses in apical ezrin and Syntaxin 3. Hepatocytes in the
      MVID patients displayed aberrant canalicular expression of the essential
      transporters MRP2 and BSEP. The pancreas showed small fragmented islets and a
      decrease in apical ezrin in pancreatic ducts. Kidney showed normal primary cilia.
      CONCLUSIONS: These findings indicate that the effects of the P660L mutation in
      MYO5B in Navajo MVID patients are not limited to the small intestine, but that
      certain tissues may be able to compensate functionally for alterations in apical
      trafficking.

PMID- 29218487
TI  - 3D true-phase polarity recovery with independent phase estimation using three
      tier stacks based region growing (3D-TRIPS).
AB  - OBJECTIVES: A postprocessing technique termed 3D true-phase polarity recovery
      with independent phase estimation using three-tier stacks based region growing
      (3D-TRIPS) was developed, which directly reconstructs phase-sensitive inversion
      recovery images without acquisition of phase-reference images. The utility of
      this technique is demonstrated in myocardial late gadolinium enhancement (LGE)
      imaging. MATERIALS AND METHODS: A data structure with three tiers of stacks was
      used for 3D-TRIPS to directly achieve reliable region growing for successful
      background-phase estimation. Fifteen patients undergoing postgadolinium 3D phase
      sensitive inversion recovery (PSIR) cardiac LGE magnetic resonance imaging (MRI)
      were recruited, and 3D-TRIPS LGE reconstructions were compared with standard
      PSIR. Objective voxel-by-voxel comparison was performed. Additionally, blinded
      review by two radiologists compared scar visibility, clinical acceptability,
      voxel polarity error, or groups and blurring. RESULTS: 3D-TRIPS efficiently
      reconstructed postcontrast phase-sensitive myocardial LGE images. Objective
      analysis showed an average 95% voxel-by-voxel agreement between 3D-TRIPS and PSIR
      images. Blinded radiologist review demonstrated similar image quality between 3D
      TRIPS and PSIR reconstruction. CONCLUSION: 3D-TRIPS provided similar image
      quality to PSIR for phase-sensitive myocardial LGE MRI reconstruction. 3D-TRIPS
      does not require acquisition of a reference image and can therefore be used to
      accelerate phase-sensitive LGE imaging.

PMID- 29218488
TI  - Effect of Body Position on Pharyngeal Swallowing Pressures Using High-Resolution
      Manometry.
AB  - The effect of body position and gravitational pull on the complex pressure-driven
      process of pharyngeal swallowing remains unknown. Using high-resolution manometry
      (HRM), this study aims to identify positional adaptations of pharyngeal
      physiology by evaluating swallowing pressure patterns in a series of inverted
      body positions. Ten healthy adults each underwent swallowing tasks with
      pharyngeal HRM at six body positions using an inversion table (0 degrees
      [upright], 45 degrees , 90 degrees [supine], 110 degrees , 135 degrees , and 180
      degrees [fully inverted]). Repeated measures ANOVA was used to assess impact of
      position on pressure parameters, and pharyngeal-UES pressure gradients translate.
      Velopharyngeal pressures varied by position (P < 0.001), with significantly
      higher pressures generated with inversion >=90 degrees , compared with upright
      and 45 degrees . Change in position did not significantly affect common
      mesopharyngeal pressures or swallowing pressure durations. UES valving mechanisms
      were preserved during inversion, with subtle variations observed in integral
      pressures (P = 0.011). Pharyngeal-UES pressure gradients changed with position (P
      < 0.01), increasing with inversion > 90 degrees  compared to upright and 45
      degrees . Mechanisms of deglutition may differ with position and relative
      direction of gravity, particularly when at > 45 degrees  inclination. Increased
      palatal pressure is generated in the upside-down position to achieve
      nasopharyngeal closure and prevent regurgitation. While other classically
      measured pressures may not consistently differ with positioning, many individuals
      exhibit adaptations in pressure gradients when inverted, likely due to a
      combination of changes in pharyngeal driving force and UES opening mechanisms.
      Identification of these changes, relative to position, further builds on our
      understanding of the adaptability of the pharyngeal swallowing system.

PMID- 29218489
TI  - Contrast-enhanced ultrasound of the kidney: a single-institution experience.
AB  - BACKGROUND: Focal renal masses are typically evaluated by means of triphasic
      contrast-enhanced CT or MRI scan but use of iodinated contrast or gadolinium is
      unsuitable for some patients. Contrast-enhanced ultrasound (CEUS) is an imaging
      alternative in this scenario but has limited availability in Ireland. AIM: The
      aim of the study was to retrospectively evaluate experience with selective use of
      CEUS for non-invasive characterization of focal renal masses in a tertiary
      referral institution in Ireland, with a particular focus on cystic renal lesions
      and the influence of CEUS on final Bosniak classification and treatment outcomes.
      METHODS: All cases of renal CEUS between 2009 and 2017 were identified. Imaging
      history, patient records, histopathology reports, urology conference notes,
      clinical follow-up details, details of lesion progression or stability on
      surveillance, biopsy and/or resection details and pre- and post-CEUS Bosniak
      scores were recorded. RESULTS: Thirty-one patients underwent renal CEUS (7 solid
      renal lesions, 21 cystic renal lesions and 3 'indeterminate' renal lesions).
      After CEUS, the CEUS-modified Bosniak score was upgraded in nine patients and
      downgraded in two patients. All three lesions upgraded from Bosniak III to IV
      were renal cell carcinomas. One of two lesions downgraded from Bosniak IV to III
      was resected (cystic nephroma) and the other showed no progression after 19
      months of surveillance. CONCLUSION: CEUS is a valuable alternative to CT in
      assessing complex cystic or solid renal lesions where iodinated CT contrast or
      gadolinium is inappropriate. CEUS can also refine the Bosniak category of
      atypical cystic renal lesions and help facilitate treatment decisions.

PMID- 29218490
TI  - Fathers Count: The Impact of Paternal Risk Factors on Birth Outcomes.
AB  - Objective To determine the contribution of paternal factors to the risk of
      adverse birth outcomes. Methods This is a retrospective cross-sectional analysis
      using birth certificate data from 2004 to 2015 retrieved from the Finger Lakes
      Regional Perinatal Data System. Primiparous women with singleton pregnancies were
      analyzed in the study. Two multivariate logistic regression models were conducted
      to assess potential paternal risk factors including age, race/ethnicity, and
      education on four birth outcomes, including preterm birth (PTB), low birthweight
      (LBW), high birthweight (HBW), and small for gestational age (SGA). Results A
      total of 36,731 singleton births were included in the analysis. Less paternal
      education was significantly related to an elevated risk of PTB, LBW, and SGA,
      even after adjustment for maternal demographic, medical, and lifestyle factors (P
      < 0.05). Paternal race/ethnicity was also significantly associated with all four
      birth outcomes (P < 0.05) while controlling for maternal factors. Older paternal
      age was associated with increased odds (OR 1.012, 95% CI 1.003-1.022) of LBW.
      Maternal race/ethnicity partially mediated the association of paternal
      race/ethnicity with HBW and SGA. Maternal education partially mediated the
      relationship between paternal education and SGA. Conclusion Paternal factors were
      important predictors of adverse birth outcomes. Our results support the inclusion
      of fathers in future studies and clinical programs aimed at reducing adverse
      birth outcomes.

PMID- 29218491
TI  - A specific amino acid residue in the catalytic site of dandelion polyphenol
      oxidases acts as 'selector' for substrate specificity.
AB  - KEY MESSAGE: Successful site-directed mutagenesis combined with in silico
      modeling and docking studies for the first time offers experimental proof of the
      role of the 'substrate selector' residue in plant polyphenol oxidases. The plant
      and fungi enzymes responsible for tissue browning are called polyphenol oxidases
      (PPOs). In plants, PPOs often occur as families of isoenzymes which are
      differentially expressed, but little is known about their physiological roles or
      natural substrates. In a recent study that explored these structure-function
      relationships, the eleven known dandelion (Taraxacum officinale) PPOs were shown
      to separate into two different phylogenetic groups differing in catalytic cavity
      architecture, kinetic parameters, and substrate range. The same study proposed
      that the PPOs' substrate specificity is controlled by one specific amino acid
      residue positioned at the entrance to the catalytic site: whereas group 1
      dandelion PPOs possess a hydrophobic isoleucine (I) at position HB2+1, group 2
      PPOs exhibit a larger, positively charged arginine (R). However, this suggestion
      was only based on bioinformatic analyses, not experiments. To experimentally
      investigate this hypothesis, we converted group 1 ToPPO-2 and group 2 ToPPO-6
      into PPO-2-I244R and PPO-6-R254I, respectively, and expressed them in E. coli. By
      performing detailed kinetic characterization and in silico docking studies, we
      found that replacing this single amino acid significantly changed the PPO's
      substrate specificity. Our findings therefore proof the role of the 'substrate
      selector' in plant PPOs.

PMID- 29218492
TI  - Efficacy of Secukinumab in the Treatment of Moderate to Severe Plaque Psoriasis
      in the North American Subgroup of Patients: Pooled Analysis of Four Phase 3
      Studies.
AB  - INTRODUCTION: Demographic and disease characteristics may impact response to
      psoriasis therapies. The objective of this study is to explore the safety and
      efficacy profile of secukinumab in North American (NA) versus non-NA patients
      with moderate to severe psoriasis. METHODS: Data were pooled from four phase 3
      studies of secukinumab. Secukinumab (300 and 150 mg) was administered at
      baseline, weeks 1, 2, and 3, then every 4 weeks from week 4 to 48. RESULTS: Peak
      efficacy was observed at week 16 in NA and non-NA patients with secukinumab 300
      mg and secukinumab 150 mg, and disease clearance was maintained to week 52. At
      week 52 with secukinumab 300 mg, Psoriasis Area and Severity Index (PASI) 90/100
      response was achieved by 62.9%/37.9% of NA patients, respectively, and
      70.2%/42.0% of non-NA patients, respectively. At week 52 with secukinumab 150 mg,
      PASI 90/100 response was achieved by 30.9%/17.5% of NA patients, respectively,
      and 53.9%/26.9% of non-NA patients, respectively. Response to secukinumab was
      rapid, and 50% reduction in mean PASI was achieved in both groups after 2.9 weeks
      with secukinumab 300 mg and 3.7 weeks with secukinumab 150 mg. CONCLUSION:
      Despite differences in baseline characteristics, the efficacy and safety of
      secukinumab were similar among NA and non-NA patients. FUNDING: Novartis Pharma
      AG. Plain language summary available for this article.

PMID- 29218494
TI  - Efficacy of pulsed dye laser treatment for common warts is not influenced by the
      causative HPV type: a prospective study.
AB  - Verruca vulgaris (VV) is a prevalent skin condition caused by various subtypes of
      human papilloma virus (HPV). The most common causes of non-genital lesions are
      HPV types 2 and 4, and to a lesser extent types 1, 3, 26, 29, and 57. Although
      numerous therapeutic modalities exist, none is universally effective or without
      adverse events (AE). Pulsed dye laser (PDL) is a favorable option due to its
      observed efficacy and relatively low AE rate. However, it is not known which
      verrucae are most likely to respond to PDL, or whether the causative viral
      subtype influences this response. The objective of this prospective blinded study
      was to assess whether the HPV subtype was predictive of response to PDL. For that
      matter, 26 verrucae from 26 immunocompetent patients were biopsied prior to
      treatment by PDL. HPV coding sequences were isolated and genotyped using PCR
      analysis. Patients were treated by PDL (595 nm wavelength, 5 mm spot size, 1.5 ms
      pulse duration, 12 J/cm2 fluence) once a month for up to 6 months, and clinical
      response was assessed. Binary logistic regression analysis and linear logistic
      regression analysis were used in order to evaluate statistical significance.
      Different types of HPV were identified in 22 of 26 tissue samples. Response to
      treatment did not correlate with HPV type, age, or gender. As no association
      between HPV type and response to PDL therapy could be established, it is
      therefore equally effective for all HPV types and remains a favorable treatment
      option for all VV.

PMID- 29218493
TI  - Direct biological effects of fractional ultrapulsed CO2 laser irradiation on
      keratinocytes and fibroblasts in human organotypic full-thickness 3D skin models.
AB  - Molecular effects of various ablative and non-ablative laser treatments on human
      skin cells-especially primary effects on epidermal keratinocytes and dermal
      fibroblasts-are not yet fully understood. We present the first study addressing
      molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment
      using a 3D skin model that allows standardized investigations of time-dependent
      molecular changes ex vivo. While histological examination was performed to assess
      morphological changes, we utilized gene expression profiling using microarray and
      qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated
      models exhibited dose-dependent morphological changes resulting in an almost
      complete recovery of the epidermis 5 days after irradiation. On day 5 after laser
      injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an
      upregulation of genes associated with tissue remodeling and wound healing (e.g.,
      COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12
      and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On
      the other hand, we detected a downregulation of matrix metalloproteinases (e.g.,
      MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory
      cytokine IL1alpha.Overall, our findings substantiate the understanding of time
      dependent molecular changes after CO2 laser treatment. The utilized 3D skin model
      system proved to be a reliable, accurate, and reproducible tool to explore the
      effects of various laser settings both on skin morphology and gene expression
      during wound healing.

PMID- 29218495
TI  - Systemic Epstein-Barr virus-positive T-cell lymphoproliferative disorders of
      childhood with fulminant leukocytosis and tumor lysis: a case report with autopsy
      findings.
AB  - Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders
      (T-LPD) of childhood is an extremely rare disease characterized by an aggressive
      clinical course and very poor prognosis. We report an adolescent male with
      systemic EBV-positive T-LPD of childhood after primary EBV infection, resulting
      in a fatal clinical course within 9 days, along with autopsy findings. A 19-year
      old male without an immunocompromised status presented with an acute onset of
      high fever, and was hospitalized for persistent fever, vomiting and diarrhea on
      the 5th day from onset. Laboratory data showed severe thrombocytopenia, increased
      ferritin level, liver dysfunction, disseminated intravascular coagulation, and
      anti-EBV-IgM positivity. Peripheral blood smears identified a number of atypical
      lymphocytes. Bone marrow aspiration revealed many atypical various-sized
      lymphocytes with apparent nucleoli and hemophagocytosis. Atypical lymphocytes
      displayed a CD8+ T-cell phenotype with monoclonal rearrangement of T-cell
      receptors. EBV-encoded RNA was also observed in lymphoid cells by in situ
      hybridization. The patient received dexamethasone and cyclosporine with no
      improvement, and died of tumor lysis by leukocytosis on the 9th day from onset.

PMID- 29218496
TI  - Testing the Association Between Traditional and Novel Indicators of County-Level
      Structural Racism and Birth Outcomes among Black and White Women.
AB  - Despite decreases in infants born premature and at low birth weight in the United
      States (U.S.), racial disparities between Black and White women continue. In
      response, the purpose of this analysis was to examine associations between both
      traditional and novel indicators of county-level structural racism and birth
      outcomes among Black and White women. We merged individual-level data from the
      California Birth Statistical Master Files 2009-2013 with county-level data from
      the United States (U.S.) Census American Community Survey. We used hierarchical
      linear modeling to examine Black-White differences among 531,170 primiparous
      women across 33 California counties. Traditional (e.g., dissimilarity index) and
      novel indicators (e.g., Black to White ratio in elected office) were associated
      with earlier gestational age and lower birth weight among Black and White women.
      A traditional indicator was more strongly associated with earlier gestational age
      for Black women than for White women. This was the first study to empirically
      demonstrate that structural racism, measured by both traditional and novel
      indicators, is associated with poor health and wellbeing of infants born to Black
      and White women. However, findings indicate traditional indicators of structural
      racism, rather than novel indicators, better explain racial disparities in birth
      outcomes. Results also suggest the need to develop more innovative approaches to:
      (1) measure structural racism at the county-level and (2) reform public policies
      to increase integration and access to resources.

PMID- 29218497
TI  - Diabetes Prevention for African-Americans: a Scoping Review.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is the most common form of diabetes
      and is preventable in many instances. African-Americans are disproportionately
      represented in T2DM statistics. The strategies in place to prevent disease
      development in this population warrant critical examination. METHODS: A scoping
      review of literature was conducted to provide an overview of the largely
      inconsistent approach to African-American T2DM prevention research. Specific
      research questions included: (1) How are African-Americans treated in the
      existing T2DM literature? (1a) Are African-Americans primarily treated as a
      homogenous group in the literature? (1b) Has the literature addressed middle
      class African-Americans? (2) Is the T2DM prevention literature focused on primary
      or secondary prevention? The review included articles published from 1985 to
      2016, examining the methodology and approach toward African-Americans in each
      article. RESULTS: The review yielded 653 unduplicated articles. Through title,
      abstract, and full-text screenings, 381 articles were excluded. Of the remaining
      articles only 37% were focused on the prevention of T2DM development, and only
      22.7% described a participant education component. The majority of the studies
      were observational (n = 19). Only 53.5% included majority African-American
      participants. Samples ranged from 2 to 27,899 individuals, which were often
      treated as homogeneous groups in terms of income and/or education (62.3%).
      CONCLUSION: The approach to T2DM prevention in African-Americans is largely
      inconsistent, which may be contributing to stagnation in this area of research.

PMID- 29218498
TI  - The Epidemiology of Coping in African American Adults in the Jackson Heart Study
      (JHS).
AB  - Differences in coping within the African American population are not well
      understood, yet these differences may be critical to reducing stress, improving
      health, and reducing racial health disparities. Using a descriptive, exploratory
      analysis of the Jackson Heart Study (N = 5301), we examine correlations between
      coping responses and associations between coping and demographic, socioeconomic,
      psychosocial, and neighborhood factors. Overall, coping responses were not
      strongly correlated and patterns of associations between covariates and coping
      responses were largely inconsistent. The results suggest that coping varies
      substantially within this African American population and is driven mainly by
      psychosocial factors such as spirituality and interpersonal support.
      Understanding these complex relationships may inform strategies by which to
      intervene in the stress process to mitigate the effects of stress on health and
      to identify vulnerable subgroups of African Americans that might need targeted
      interventions to reduce exposure to stressors and improve coping capacities.

PMID- 29218499
TI  - Effect of CLIP3 Upregulation on Astrocyte Proliferation and Subsequent Glial Scar
      Formation in the Rat Spinal Cord via STAT3 Pathway After Injury.
AB  - Spinal cord injury (SCI) is a devastating event resulting in neuron degeneration
      and permanent paralysis through inflammatory cytokine overproduction and glial
      scar formation. Presently, the endogenous molecular mechanisms coordinating glial
      scar formation in the injured spinal cord remain elusive. Signal transducer and
      activator of transcription 3 (STAT3) is a well-known transcription factor
      particularly involving in cell proliferation and inflammation in the lesion site
      following SCI. Meanwhile, CAP-Gly domain containing linker protein 3(CLIP3), a
      vital cytoplasmic protein, has been confirmed to providing an optimal conduit for
      intracellular signal transduction and interacting with STAT3 with mass
      spectrometry analysis. In this study, we aimed to identify the expression of
      CLIP3 in the spinal cord as well as its role in mediating astrocyte activation
      and glial scar formation after SCI by establishing an acute traumatic SCI model
      in male adult rats. Western blot analysis revealed that CLIP3 increased gradually
      after injury, reached a peak at day 3. The immunohistochemistry staining showed
      the same result in white matter. With double immunofluorescence staining, we
      found that CLIP3 was expressed in glial cells and significant changes of CLIP3
      expression occurred in astrocytes during the pathological process. Statistical
      analysis demonstrated there was a correlation between the number of positive
      cells stained by CLIP3 and STAT3 in the spinal cord after SCI. Co
      immunoprecipitation further indicated that CLIP3 interacted with STAT3 in the
      injured spinal cord. Taken together, our study clearly suggested that CLIP3
      played an essential role in astrocyte activation, associating with the STAT3
      pathway activation induced by SCI.

PMID- 29218500
TI  - An Initial Investigation of Individual Rate-of-Play Preferences and Associations
      with EGM Gambling Behavior.
AB  - Electronic gambling machines (EGMs) show a strong association with gambling
      problems. The high speed of gaming offered by modern EGMs allows playing numerous
      games in a short span of time, which is thought to contribute to attentional
      distraction, increased spending and prolonged play. However, the relationship
      between EGM speeds and potentially risk-related gambling behavior remains
      unclear. We introduce a novel approach to investigating the role of gaming speed
      in EGM gambling behavior by examining 'individual rate-of-play' (I-ROP) during
      simulated EGM gambling. A community sample of male regular gamblers (N = 72)
      played virtual slot machines in pairs offering sequentially adjusted game speeds
      towards the estimation of a behaviorally expressed preference speed, or I-ROP.
      This initial experiment aimed to explore the variability of I-ROPs during
      simulated EGM gambling, and examine behavior while playing EGMs at speeds
      relative to their I-ROP. Estimated I-ROPs ranged from less than one half second
      to over seven seconds and were negatively associated with cognitive ability, but
      not related to problem gambling severity, impulsiveness, or gambling-related
      cognitions. Subsequent gambling sessions on EGMs offering individually calibrated
      faster and slower gaming speeds were associated with greater and reduced risk
      related gambling behaviors respectively. I-ROPs represent a potentially
      informative construct for exploring influences of gaming speed on gambling
      behavior, and may lend insight into potential risk-related behavior an individual
      vulnerability with respect to commercially available EGMs that warrants
      additional research.

PMID- 29218502
TI  - Lower preoperative Hounsfield unit values are associated with intra-operative
      fractures in cementless bipolar hemiarthroplasty.
AB  - : The use of Hounsfield units (HU) from CT scanning to assess regional BMD has
      been described. Therefore, we evaluated whether HU could be used to identify
      osteoporosis of the proximal part of the femur. The results showed that HU
      assessment is associated with the presence of intra-operative fracture during
      arthroplasty. INTRODUCTION: The aim with this study was to determine the
      association of preoperative Hounsfield unit (HU) in hip computed tomography (CT)
      with intra-operative osteoporotic fracture during cementless hemiarthroplasty.
      METHODS: In this retrospective study, we reviewed all patients who underwent
      cementless bipolar hemiarthroplasty for femoral neck fractures between 2014 and
      2016. Patients with intra-operative metaphyseal fractures (n = 25) during surgery
      were identified from a retrospectively collected patient database and matched
      with nonfracture controls (n = 75) on the basis of age and sex. The differences
      between patients with intra-operative fractures and without intra-operative
      fractures were compared regarding preoperative HU. Correlations of HU value of
      femur neck with BMD and T scores were determined. RESULTS: Analysis of HU values
      at the fracture level showed a significantly lower value in the fracture group
      than in the controls (1186 vs 1340, p = 0.005). The correlation between HU and
      BMD of femur neck was significant (r 2 = 0.347; p < 0.001). The correlation
      between HU of femur neck and BMD of spine was also significant (r 2 = 0.133; p <
      0.001). CONCLUSIONS: HU assessment using preoperative CT scan is associated with
      the presence of intra-operative fracture during bipolar hemiarthroplasty. We
      believe that HU values of the proximal femur could be used to assess local bone
      quality.

PMID- 29218501
TI  - Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000-2016: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: There are very few options to treat multidrug-resistant bacterial
      infections in children. A major barrier is the duration and complexity of
      regulatory trials of new antibiotics. Extrapolation of safety data from adult
      trials could facilitate drug development for children. OBJECTIVE: We performed a
      systematic review on the safety of antibiotic clinical trials (CTs) in children
      (0-18 years) to evaluate the overall quality of safety trials conducted in
      children and to determine if age-specific adverse events (AEs) could be
      identified for specific antibiotic classes. DATA SOURCES: We searched the
      MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov electronic databases for trials
      conducted between 2000 and 2016. STUDY SELECTION: All trials in which safety was
      declared a primary or secondary endpoint were included. Exclusion criteria were
      (1) topical or inhalational route of administration; (2) non-infectious
      conditions; (3) administration for prophylaxis rather than treatment; (4)
      selected population (i.e. cystic fibrosis, malignancies, HIV and tuberculosis);
      and (5) design other than randomized controlled trials. Trials reporting data on
      both adults and children were included only if paediatric results were reported
      separately. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted
      the data. To assess the quality of published trials, the Extension for harms for
      Consolidated Standards of Reporting Trials (CONSORT) Statement 2004 was used.
      MAIN OUTCOME AND MEASURE: In order to quantitatively assess the rate of
      developing AEs by drug class, the numbers of overall and body-system-specific AEs
      were collected for each study arm, and then calculated per single drug class as
      median and interquartile range (IQR) of the proportions across CTs. The AEs most
      frequently reported were compared in the meta-analysis by selecting the CTs on
      the most represented drug classes. RESULTS: Eighty-three CTs were included,
      accounting for 27,693 children. Overall, 69.7% of CONSORT items were fully
      reported. The median proportion of children with any AE was 22.5%, but did not
      exceed 8% in any single body system. Serious drug-related AEs and drug-related
      discontinuations were very rare (median 0.3 and 0.9%, respectively). Limitations
      included the inability to stratify by age group, particularly neonates.
      CONCLUSIONS AND RELEVANCE: Overall, AEs in paediatric antibiotic CTs were
      predictable and class-specific, and no unexpected (age-specific) side effects
      were identified. Smaller, open-label, dose-finding, high-quality, single-arm
      pharmacokinetic trials seem potentially sufficient for certain common antibiotic
      classes, extrapolating well-established safety profiles determined from large
      adult efficacy trials. This approach could reduce duration and enhance subsequent
      registration of urgently needed new antibiotics. This will need to be combined
      with enhanced methods of pharmacovigilance for monitoring of emerging AEs in
      routine clinical practice.

PMID- 29218503
TI  - Differential Alterations in Metabolism and Proteolysis-Related Proteins in Human
      Parkinson's Disease Substantia Nigra.
AB  - Parkinson's disease is the most common neurodegenerative disorder after
      Alzheimer's disease, with the majority of cases being sporadic or "idiopathic".
      The aetiology of the sporadic form is still unknown, but there is a broad
      consensus that Parkinson's disease involves multiple pathways. In previous human
      post-mortem studies investigating substantia nigra of parkinsonian subjects, gene
      expression alterations in various metabolic pathways including protein folding,
      trafficking, aggregation, ubiquitination and oxidative stress were found. These
      studies revealed transcriptomic dysregulation of various genes, amongst others
      Skp1A and PSMC4 (part of ubiquitin-proteasome system), HSC70 (belonging to the
      chaperone family) and ALDH1A1 (an enzyme involved in the catabolism of dopamine).
      To investigate whether these alterations are manifested at the protein level, we
      performed immunohistochemical analysis in the substantia nigra of Parkinson's
      disease and compared them to Alzheimer's disease and non-neurological post-mortem
      controls. We were able to confirm cell-specific reductions in the protein content
      of ALHD1A1 and Skp1A in the dopaminergic neurons of the substantia nigra of
      Parkinsonian patients compared to Alzheimer's and control subjects. Furthermore,
      we observed particular distribution for HSC70 and PSMC4 in the cytoplasm and
      accumulation within Lewy body in the dopaminergic neurons of the substantia nigra
      in Parkinson patients. These findings, together with previous evidence, suggest a
      malfunction of the ubiquitin-proteasome and possible autophagy systems as major
      players in protein misfolding and aggregation in Parkinson's disease.
      Nevertheless, this needs further proof, possibly with trajectory time line.

PMID- 29218504
TI  - Temporal-Spatial Profiling of Pedunculopontine Galanin-Cholinergic Neurons in the
      Lactacystin Rat Model of Parkinson's Disease.
AB  - Parkinson's disease (PD) is conventionally seen as resulting from single-system
      neurodegeneration affecting nigrostriatal dopaminergic neurons. However,
      accumulating evidence indicates multi-system degeneration and neurotransmitter
      deficiencies, including cholinergic neurons which degenerate in a brainstem
      nucleus, the pedunculopontine nucleus (PPN), resulting in motor and cognitive
      impairments. The neuropeptide galanin can inhibit cholinergic transmission, while
      being upregulated in degenerating brain regions associated with cognitive
      decline. Here we determined the temporal-spatial profile of progressive
      expression of endogenous galanin within degenerating cholinergic neurons, across
      the rostro-caudal axis of the PPN, by utilizing the lactacystin-induced rat model
      of PD. First, we show progressive neuronal death affecting nigral dopaminergic
      and PPN cholinergic neurons, reflecting that seen in PD patients, to facilitate
      use of this model for assessing the therapeutic potential of bioactive peptides.
      Next, stereological analyses of the lesioned brain hemisphere found that the
      number of PPN cholinergic neurons expressing galanin increased by 11%, compared
      to sham-lesioned controls, and increasing by a further 5% as the
      neurodegenerative process evolved. Galanin upregulation within cholinergic PPN
      neurons was most prevalent closest to the intra-nigral lesion site, suggesting
      that galanin upregulation in such neurons adapt intrinsically to
      neurodegeneration, to possibly neuroprotect. This is the first report on the
      extent and pattern of galanin expression in cholinergic neurons across distinct
      PPN subregions in both the intact rat CNS and lactacystin-lesioned rats. The
      findings pave the way for future work to target galanin signaling in the PPN, to
      determine the extent to which upregulated galanin expression could offer a viable
      treatment strategy for ameliorating PD symptoms associated with cholinergic
      degeneration.

PMID- 29218505
TI  - Antibacterial and Antibiofilm Activity of Lactic Acid Bacteria Isolated from
      Traditional Artisanal Milk Cheese from Northeast China Against Enteropathogenic
      Bacteria.
AB  - The present study aims to investigate the probiotic properties of novel strains
      of lactic acid bacteria isolated from traditional artisanal milk cheese from
      Northeast China and to explore their antibacterial activity against
      enteropathogenic bacteria. Of the 321 isolates, 86 exhibited survival in low pH,
      resistance to pancreatin, and tolerance to bile salts; of these, 12 inhibited the
      growth of more than seven enteropathogenic bacteria and exhibited antibiofilm
      activities against Staphylococcus aureus CMCC26003 and/or Escherichia coli
      CVCC230. Based on 16S ribosomal RNA sequence analysis, the 12 isolates were
      assigned to Lactobacillus plantarum (7), Lactobacillus helveticus (3),
      Pediococcus acidilactici (1), and Enterococcus faecium (1) species. In addition,
      5 of the 12 strains were susceptible to most of the tested antibiotics.
      Furthermore, four strains with sensitivity to antibiotics showed significantly
      high levels of hydrophobicity similar to or better than the reference strain
      Lactobacillus rhamnosus GG. Moreover, three strains were confirmed safe through
      non-hemolytic activities and bacterial translocation. Overall, the selected Lact.
      plantarum 27053 and 27172 and Lact. helveticus 27058 strains can be considered
      potential probiotic strains and candidates for further application in functional
      food and prevention or treatment of gastrointestinal diseases.

PMID- 29218506
TI  - In Silico Discovery of Novel Ligands for Antimicrobial Lipopeptides for Computer
      Aided Drug Design.
AB  - The increase in antibiotic-resistant strains of pathogens has created havoc
      worldwide. These antibiotic-resistant pathogens require potent drugs for their
      inhibition. Lipopeptides, which are produced as secondary metabolites by many
      microorganisms, have the ability to act as potent safe drugs. Lipopeptides are
      amphiphilic molecules containing a lipid chain bound to the peptide. They exhibit
      broad-spectrum activities against both bacteria and fungi. Other than their
      antimicrobial properties, they have displayed anti-cancer properties as well, but
      their mechanism of action is not understood. In silico drug design uses computer
      simulation to discover and develop new drugs. This technique reduces the need of
      expensive and tedious lab work and clinical trials, but this method becomes a
      challenge due to complex structures of lipopeptides. Specific agonists (ligands)
      must be identified to initiate a physiological response when combined with a
      receptor (lipopeptide). In silico drug design and homology modeling talks about
      the interaction between ligands and the binding sites. This review summarizes the
      mechanism of selected lipopeptides, their respective ligands, and in silico drug
      design.

PMID- 29218507
TI  - Clustering based on unsupervised binary trees to define subgroups of cancer
      patients according to symptom severity in cancer.
AB  - BACKGROUND: Studies have suggested that clinicians do not feel comfortable with
      the interpretation of symptom severity, functional status, and quality of life
      (QoL). Implementation strategies of these types of measurements in clinical
      practice imply that consensual norms and guidelines regarding data interpretation
      are available. The aim of this study was to define subgroups of patients
      according to the levels of symptom severity using a method of interpretable
      clustering that uses unsupervised binary trees. METHODS: The patients were
      classified using a top-down hierarchical method: Clustering using Unsupervised
      Binary Trees (CUBT). We considered a three-group structure: "high", "moderate",
      and "low" level of symptom severity. The clustering tree was based on three
      stages using the 9-symptom scale scores of the EORTC QLQ-C30: a maximal tree was
      first developed by applying a recursive partitioning algorithm; the tree was then
      pruned using a criterion of minimal dissimilarity; finally, the most similar
      clusters were joined together. Inter-cluster comparisons were performed to test
      the sample partition and QoL data. RESULTS: Two hundred thirty-five patients with
      different types of cancer were included. The three-cluster structure classified
      143 patients with "low", 46 with "moderate", and 46 with "high" levels of symptom
      severity. This partition was explained by cut-off values on Fatigue and Appetite
      Loss scores. The three clusters consistently differentiated patients based on the
      clinical characteristics and QoL outcomes. CONCLUSION: Our study suggests that
      CUBT is relevant to define the levels of symptom severity in cancer. This finding
      may have important implications for helping clinicians to interpret symptom
      profiles in clinical practice, to identify individuals at risk for poorer
      outcomes and implement targeted interventions.

PMID- 29218509
TI  - Protective effect of cadmium-induced autophagy in rat renal mesangial cells.
AB  - Cadmium damages renal cells, and in particular may cause mesangial cell death by
      necrosis or apoptosis, depending on exposure conditions in cultured cells.
      However, there is an uncertainty as to whether Cd2+-induced autophagy can protect
      mesangial cells against these other mechanisms of cell death. We have used
      autophagy-incompetent mouse embryonic fibroblast (MEF) cells lacking the Atg16
      gene, as well as cultured rat mesangial cells (RMC) in which Atg16 has been
      silenced, to examine this issue. Measuring the processing of LC3-I to LC3-II and
      expression of sequestosome-1 (p62), we define conditions under which RMC can be
      induced to undergo autophagy in response to 0-20 uM CdCl2. Similarly, Cd2+ can
      initiate autophagy in MEF cells. However, when autophagy is compromised, either
      by gene knockout in MEF cells or by RNA silencing in RMC, cell viability is
      decreased, and concomitantly a Cd2+ dose-dependent increase in pro-caspase-3
      cleavage indicates the initiation of apoptotic cell death. In contrast to some
      previous reports, Cd2+-induced autophagy is not correlated with increased levels
      of cellular reactive oxygen species but, among a panel of kinases investigated,
      is suppressed by inhibition of the Jun kinase. We conclude that concentrations of
      Cd2+ that initiate autophagy may afford renal mesangial cells some degree of
      protection against other modes (apoptosis, necrosis) of cell death.

PMID- 29218508
TI  - Use of HuH6 and other human-derived hepatoma lines for the detection of
      genotoxins: a new hope for laboratory animals?
AB  - Cell lines which are currently used in genotoxicity tests lack enzymes which
      activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used
      which reflect their metabolism in humans only partly; as a consequence misleading
      results are often obtained. Previous findings suggest that certain liver cell
      lines express phase I/II enzymes and detect promutagens without activation;
      however, their use is hampered by different shortcomings. The aim of this study
      was the identification of a suitable cell line. The sensitivity of twelve hepatic
      cell lines was investigated in single cell gel electrophoresis assays.
      Furthermore, characteristics of these lines were studied which are relevant for
      their use in genotoxicity assays (mitotic activity, p53 status, chromosome
      number, and stability). Three lines (HuH6, HCC1.2, and HepG2) detected
      representatives of five classes of promutagens, namely, IQ and PhIP (HAAs), B(a)P
      (PAH), NDMA (nitrosamine), and AFB1 (aflatoxin), and were sensitive towards
      reactive oxygen species (ROS). In contrast, the commercially available line
      HepaRG, postulated to be a surrogate for hepatocytes and an ideal tool for
      mutagenicity tests, did not detect IQ and was relatively insensitive towards ROS.
      All other lines failed to detect two or more compounds. HCC1.2 cells have a high
      and unstable chromosome number and mutated p53, these features distract from its
      use in routine screening. HepG2 was frequently employed in earlier studies, but
      pronounced inter-laboratory variations were observed. HuH6 was never used in
      genotoxicity experiments and is highly promising, it has a stable karyotype and
      we demonstrated that the results of genotoxicity experiments are reproducible.

PMID- 29218510
TI  - Biography-Q. Ping Dou.

PMID- 29218512
TI  - (E)merging directions on air pollution and climate change research in
      Mediterranean Basin ecosystems.

PMID- 29218511
TI  - Optical monitoring of cerebral microcirculation in neurointensive care.
AB  - Continuous optical monitoring of local cerebral microcirculation could benefit
      neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim
      of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse
      reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation
      and oxygen saturation (SO2) in the neurointensive care unit (NICU). A fiber optic
      probe was designed for intraparenchymal use and connected to LDF and DRS for
      assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and
      SO2 in the brain. The optically monitored parameters were compared with
      conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25
      to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to
      2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate.
      Median and interquartiles of SO2 were 17.4 (15.7 to 19.8) %. The lack of
      correlation between local perfusion and cerebral perfusion pressure indicated
      intact cerebral autoregulation. The systems were capable of monitoring both local
      perfusion and SO2 with stable signals in the NICU over 4 days. Further clinical
      studies are required to evaluate the optical systems' potential for assessing the
      onset of secondary brain injury.

PMID- 29218513
TI  - Expression and Purification of Rat Glucose Transporter 1 in Pichia pastoris.
AB  - Large amounts of pure and homogenous protein are a prerequisite for several
      biochemical and biophysical analyses, and in particular if aiming at resolving
      the three-dimensional protein structure. Here we describe the production of the
      rat glucose transporter 1 (GLUT1), a membrane protein facilitating the transport
      of glucose in cells. The protein is recombinantly expressed in the yeast Pichia
      pastoris. It is easily maintained and large-scale protein production in shaker
      flasks, as commonly performed in academic research laboratories, results in
      relatively high yields of membrane protein. The purification protocol describes
      all steps needed to obtain a pure and homogenous GLUT1 protein solution,
      including cell growth, membrane isolation, and chromatographic purification
      methods.

PMID- 29218514
TI  - Crystallization and Structural Determination of the Human Glucose Transporters
      GLUT1 and GLUT3.
AB  - Overexpression, purification, and crystallization of eukaryotic membrane proteins
      represent a major challenge for structural biology. In recent years, we have
      solved the crystal structures of the human glucose transporters GLUT1 in the
      inward-open conformation at 3.17 A resolution and GLUT3 in the outward-open and
      occluded conformations at 2.4 and 1.5 A resolutions, respectively. Structural
      elucidation of these transporters in three distinct functional states reveal the
      molecular basis for the alternating access transport cycle of this prototypal
      solute carrier family. It established the molecular foundation for future dynamic
      and kinetic investigations of these GLUTs, and will likely facilitate structure
      based ligand development. In this chapter, we present the detailed protocols of
      recombinant protein expression, purification, and crystallization of GLUT1 and
      GLUT3, which may help the pursuit of structural elucidation of other eukaryotic
      membrane proteins.

PMID- 29218515
TI  - Screening and Scale-Up of GLUT Transporter Constructs Suitable for Biochemical
      and Structural Studies.
AB  - Identifying membrane proteins that can be produced and isolated in homogenous
      form in detergent is a lengthy trial-and-error process that can be facilitated by
      fluorescence-based screening approaches. We describe (1) the strategy and
      protocol of cloning by homologous recombination, (2) whole-cell and in-gel
      fluorescence measurements to estimate GLUT-GFP fusion protein yields, (3) use of
      size-exclusion chromatography monitored by fluorescence (FSEC) for assessing the
      homogeneity of the GLUT-GFP fusion proteins, and (4) the protocol for large-scale
      production and purification of the Bos taurus GLUT5 construct that enabled its
      crystal structure determination.

PMID- 29218516
TI  - GLUT Characterization Using Frog Xenopus laevis Oocytes.
AB  - Xenopus laevis oocytes are a useful heterologous expression system for expressing
      glucose transporters (GLUTs) and examining their functions. In this chapter, we
      provide a detailed protocol on oocyte extraction and preparation for GLUT9
      protein expression. Furthermore, we describe the determination of GLUT9
      overexpression level by biotinylation and Western blotting analysis. Finally, we
      also describe how GLUT9-expressing oocytes can be used to measure urate kinetics
      by radioisotopes as well as two-microelectrode voltage clamping techniques.

PMID- 29218517
TI  - Glucose Uptake in Heterologous Expression Systems.
AB  - Understanding the physiological regulation of glucose transport requires the
      analysis of transporters, like GLUT1, in diverse tissue types. We document the
      utility of viral vectors for the stable expression of wild-type and modified
      GLUT1 transporter in different types of mammalian cells. Once expression of the
      alleles has been confirmed by Western blotting, the effect of specific mutations
      on the regulation of glucose transport can be measured through a previously
      described radiolabeled glucose transport assay. Although this discussion is
      focused on the GLUT1 transporter, these techniques are easily transferrable to
      other glucose transporters.

PMID- 29218518
TI  - Evaluating the Efficacy of GLUT Inhibitors Using a Seahorse Extracellular Flux
      Analyzer.
AB  - Glucose is metabolized through anaerobic glycolysis and aerobic oxidative
      phosphorylation (OXPHOS). Perturbing glucose uptake and its subsequent metabolism
      can alter both glycolytic and OXPHOS pathways and consequently lactate and/or
      oxygen consumption. Production and secretion of lactate, as a consequence of
      glycolysis, leads to acidification of the extracellular medium. Molecular oxygen
      is the final electron acceptor in the electron transport chain, facilitating
      oxidative phosphorylation of ADP to ATP. The alterations in extracellular
      acidification and/or oxygen consumption can thus be used as indirect readouts of
      glucose metabolism and assessing the impact of inhibiting glucose transport
      through specific glucose transporters (GLUTs). The Seahorse bioenergetics
      analyzer can measure both the oxygen consumption rate (OCR) and extracellular
      acidification rate (ECAR). The proposed methodology affords a robust, high
      throughput method to screen for GLUT inhibition in cells engineered to express
      specific GLUTs, providing live cell read-outs upon GLUT inhibition.

PMID- 29218519
TI  - Glucose Transport Activity Measured in Giant Vesicles.
AB  - Incorporation of membrane proteins and internal reporter systems directly into
      giant vesicles, during their formation from a hydrogel surface, has emerged as a
      promising new concept in membrane protein characterization. Here, we provide the
      detailed protocol for a glucose transporter activity assay based on giant
      vesicles containing a fluorescent enzyme-linked reporter system internally. This
      assay is applicable for the functional analysis of a variety of hexose
      transporting proteins. We furthermore believe that it can aid in the development
      of drugs targeting hexose transporters.

PMID- 29218520
TI  - Design, Synthesis, and Evaluation of GLUT Inhibitors.
AB  - The Warburg effect describes how most cancer cells exhibit higher-than-normal
      glucose consumption, not only under hypoxic conditions, but also when normal
      oxygen levels are present. Although glucose transporter 1 (GLUT1) has been found
      to play a key role in the cellular uptake of glucose, especially in cancer cells,
      where it is generally overexpressed, it has not been given consideration as a
      suitable target for the development of anticancer drugs. In this chapter, an
      example of molecular design and realization of novel GLUT1 inhibitors, including
      in silico modeling, chemical synthesis, and biological characterization, is
      provided. This process started with the identification of a focused series of
      oxime derivatives, originally designed as estrogen receptor (ER) ligands, which
      were structurally optimized in order to direct their activity towards GLUT1 and
      to minimize their binding to the ERs, leading to the production of efficient and
      selective inhibitors of glucose uptake in cancer cells.

PMID- 29218521
TI  - Applying Microfluidic Systems to Study Effects of Glucose at Single-Cell Level.
AB  - Microfluidic systems in combination with microscopy (e.g., fluorescence) can be a
      powerful tool to study, at single-cell level, the behavior and morphology of
      biological cells after uptake of glucose. Here, we briefly discuss the advantages
      of using microfluidic systems. We further describe how microfluidic systems are
      fabricated and how they are utilized. Finally, we discuss how the large amount of
      data can be analyzed in a "semi-automatic" manner using custom-made software. In
      summary, we provide a guide to how to use microfluidic systems in single-cell
      studies.

PMID- 29218522
TI  - A Growth-Based Screening System for Hexose Transporters in Yeast.
AB  - As the simplest eukaryotic model system, the unicellular yeast Saccharomyces
      cerevisiae is ideally suited for quick and simple functional studies as well as
      for high-throughput screening. We generated a strain deficient for all endogenous
      hexose transporters, which has been successfully used to clone, characterize, and
      engineer carbohydrate transporters from different source organisms. Here we
      present basic protocols for handling this strain and characterizing sugar
      transporters heterologously expressed in it.

PMID- 29218523
TI  - Identification of Insulin-Activated Rab Proteins in Adipose Cells Using Bio-ATB
      GTP Photolabeling Technique.
AB  - We have recently developed a photolabeling method to identify GTP-loaded Rab
      proteins. The new biotinylated GTP analogue (Bio-ATB-GTP) binds to GTP-binding
      proteins and after a UV irradiation a covalent bond is formed between the protein
      and the photoreactive diazirine group on the photolabel. The tagged protein can
      then be isolated and detected using the classic biotin-streptavidin interaction.
      In this chapter, we describe the Bio-ATB-GTP photolabel and discuss the
      advantages of using this photolabeling approach to detect GTP-loaded Rab proteins
      compared to other existing methodologies. We also describe a step-by-step
      procedure for detecting the activated state of a Rab protein in primary rat
      adipocytes.

PMID- 29218524
TI  - Total Internal Reflection Fluorescence Microscopy to Study GLUT4 Trafficking.
AB  - Total internal reflection fluorescence (TIRF) microscopy is a powerful method
      that allows examination of plasma membrane close events in real time. The last
      decade, the method has successfully been used to explore GLUT4 translocation in
      adipocytes. Here, we describe the procedure for studying GLUT4 trafficking using
      TIRF microscopy in isolated primary adipocytes.

PMID- 29218525
TI  - Translocation and Redistribution of GLUT4 Using a Dual-Labeled Reporter Assay.
AB  - It is crucial to determine the regulation of GLUT4 translocation and
      redistribution to the plasma membrane. The HA-GLUT4-GFP dual-reporter construct
      has become an important tool in the assessment of GLUT4 recycling in cultured
      adipocytes and myocytes. Through the use of light microscopy, this reporter
      construct allows for visualization of GLUT4 specifically at the cell surface or
      GLUT4 that has recycled from the cell surface while simultaneously marking the
      total GLUT4 pool. Here, we discuss and outline the general application of this
      reporter construct and its use in evaluating GLUT4 translocation within cultured
      adipocytes.

PMID- 29218526
TI  - GLUT4 Translocation in Single Muscle Cells in Culture: Epitope Detection by
      Immunofluorescence.
AB  - GLUT4 is the major glucose transporter in skeletal muscle. GLUT4 cycles to and
      from the plasma membrane and its exocytic rate is accelerated by insulin and
      muscle contraction to achieve a new steady state with more GLUT4 proteins at the
      muscle cell surface. To gain a better understanding of the molecular and cellular
      mechanisms that govern GLUT4 protein recycling, we developed an in vitro model in
      which myc-epitope-tagged GLUT4 or GLUT4-GFP is expressed in L6 skeletal muscle
      cells. The myc-epitope is inserted into an exofacial domain that is accessible to
      anti-myc antibodies from the outside of non-permeabilized cells, allowing one to
      count the number of transporters at the cell surface. This enables one to perform
      single-cell analysis using confocal fluorescence microscopy to quantify cell
      surface GLUT4myc or GLUT4myc-GFP in cells co-transfected with diverse cDNA
      constructs, treated with siRNAs, or co-stained with antibodies for other proteins
      of interest. Herein, we describe the methodology to perform these experimental
      approaches in insulin-stimulated L6 muscle cells.

PMID- 29218527
TI  - Glucose Transport: Methods for Interrogating GLUT4 Trafficking in Adipocytes.
AB  - In this chapter we detail methods for the systematic dissection of GLUT4
      trafficking. The methods described have been optimized for cultured 3T3-L1
      adipocytes, but can be readily adapted to other cell types.

PMID- 29218528
TI  - Proximity Ligation Assay to Study the GLUT4 Membrane Trafficking Machinery.
AB  - In this chapter a detailed protocol of proximity ligation assay (PLA) is
      described thoroughly. PLA is a technique that allows detection of protein
      associations in situ, providing a sensitive and selective approach for protein
      protein interaction studies. We demonstrate the technique by applying it for
      trafficking studies of the facilitative glucose transporter GLUT4. Trafficking of
      GLUT4 from perinuclear depots to the plasma membrane is regulated by insulin in
      adipocytes and muscle cells, and mediated by formation of functional SNARE
      complexes containing Syntaxin4, SNAP23, and VAMP2. The Sec1/Munc18 (SM) protein
      Munc18c also plays a key role in insulin-stimulated GLUT4 translocation via a
      series of different interactions with the SNARE complex and/or with the SNARE
      proteins individually. Studying the interactions that occur between SNARE
      proteins themselves and also with Munc18c in insulin-responsive cells is critical
      to further understand SNARE protein function and GLUT4 trafficking mechanism in
      general.

PMID- 29218529
TI  - Quantification of Cell-Surface Glucose Transporters in the Heart Using a
      Biotinylated Photolabeling Assay.
AB  - The biotinylated photolabeling assay enables quantification of cell-surface
      glucose transporters (GLUTs). This technique has been successfully applied to
      quantify the cell-surface GLUT protein content in striated muscles and adipose
      tissue, as a means to evaluate GLUT trafficking. Here, we describe the detailed
      method of quantifying the cell-surface content of several GLUT isoforms (1, 4, 8,
      and 12) in isolated cardiac myocytes, as well as in the intact perfused atria and
      ventricle.

PMID- 29218530
TI  - Tracking GLUT2 Translocation by Live-Cell Imaging.
AB  - The facilitative glucose transporter (GLUT) family plays a key role in metabolic
      homeostasis, controlling the absorption rates and rapid response to changing
      carbohydrate levels. The facilitative GLUT2 transporter is uniquely expressed in
      metabolic epithelial cells of the intestine, pancreas, liver, and kidney. GLUT2
      dysfunction is associated with several pathologies, including Fanconi-Bickel
      syndrome, a glycogen storage disease, characterized by growth retardation and
      renal dysfunction. Interestingly, GLUT2 activity is modulated by its cellular
      localization. Membrane translocation specifically regulates GLUT2 activity in
      enterocytes, pancreatic beta-cells, hepatocytes, and proximal tubule cells. We
      have established a system to visualize and quantify GLUT2 translocation, and its
      dynamics, by live imaging of a mCherry-hGLUT2 fusion protein in polarized
      epithelial cells. This system enables testing of putative modulators of GLUT2
      translocation, which are potential drugs for conditions of impaired glucose
      homeostasis and associated nephropathy.

PMID- 29218531
TI  - GLUT2-Expressing Neurons as Glucose Sensors in the Brain: Electrophysiological
      Analysis.
AB  - Brain glucose sensing plays an essential role in the regulation of energy
      homeostasis. Recent publications report that neurons expressing glucose
      transporter GLUT2 act as glucose sensors in different regions of the brain and
      contribute to the control of glucose homeostasis and feeding behavior. In this
      chapter we describe the methods used to explore glucose sensing in genetically
      tagged GLUT2-expressing neurons with slice electrophysiology.

PMID- 29218532
TI  - ?

PMID- 29218533
TI  - ?

PMID- 29218536
TI  - Site fidelity facilitates pair formation in aggregations of coral reef
      cardinalfish.
AB  - Colonial animals often form stable pair bonds, returning to the same site to
      breed with the same partner every year. Familiarity with both partner and
      breeding site has the potential to enhance an individual's reproductive success.
      However, it is often unknown whether the mating system arises because of site
      fidelity, mate fidelity or both. Here, observational and experimental studies are
      used to identify causal links between site fidelity and pair formation in a group
      living coral reef cardinalfish, Sphaeramia nematoptera. A long-term field tagging
      study was undertaken to quantify site and mate attachment. This was followed by
      both mate removal and mate transplant experiments to test whether the prolonged
      association with home sites was primarily because of mate or site fidelity. Adult
      S. nematoptera exhibited a prolonged association with home sites and partners,
      with some pairs lasting more than 4 months at the same site. A Bayesian mixed
      effect model showed that individuals in pairs were more likely to remain site
      attached, regardless of sex and maturity. Following mate removal, 78% of S.
      nematoptera found a new partner within 2 weeks on the same site, supporting the
      hypothesis that individuals primarily exhibit site fidelity. This was confirmed
      by the partner translocation experiment, with only 1 of 24 fish following their
      translocated partner to a new site. In these cardinalfish, strong site attachment
      facilitates long-lasting pair bonds, as well as new pair formation when
      necessary, suggesting that site rather than mate fidelity is the major driver of
      the reproductive system.

PMID- 29218537
TI  - Cumulative herbivory outpaces compensation for early floral damage on a
      monocarpic perennial thistle.
AB  - Floral herbivory represents a major threat to plant reproductive success, driving
      the importance of plant tolerance mechanisms that minimize fitness costs.
      However, the cumulative insect herbivory plants experience under natural
      conditions complicates predictions about tolerance contributions to net fitness.
      Apical damage can lead to compensatory seed production from late season flowering
      that ameliorates early season fitness losses. Yet, the compensation realized
      depends on successful development and herbivore escape by later season flowers.
      Using monocarpic perennial Cirsium canescens, we quantified seed-reproductive
      fitness of plants with vs. without experimental damage to the early-developing
      large apical flower head, with and without a 30-40% herbivory reduction on
      subsequent flower heads, for two flowering cohorts. Plants with reduced herbivory
      clearly demonstrated the release of apical dominance and compensation, not
      overcompensation, for apical damage via greater seed maturation by later flower
      heads. In contrast, plants that experienced ambient herbivory levels on
      subsequent heads undercompensated for early apical damage. Individuals had lower
      total seed set when the apical head was damaged. Compensation was, therefore,
      possible through a small increase in total flower heads, caused by a higher rate
      of floral bud survival, and a higher seed maturation rate by subsequent heads,
      leading to more viable seeds per matured flower head. With ambient cumulative
      floral herbivory, compensation for apical damage was not sufficient to improve
      fitness. Variation in the intensity of biological interactions played a role in
      the success of plant tolerance as a mechanism to maximize individual fitness.

PMID- 29218538
TI  - Belowground competition drives invasive plant impact on native species regardless
      of nitrogen availability.
AB  - Plant invasions and eutrophication are pervasive drivers of global change that
      cause biodiversity loss. Yet, how invasive plant impacts on native species, and
      the mechanisms underpinning these impacts, vary in relation to increasing
      nitrogen (N) availability remains unclear. Competition is often invoked as a
      likely mechanism, but the relative importance of the above and belowground
      components of this is poorly understood, particularly under differing levels of N
      availability. To help resolve these issues, we quantified the impact of a
      globally invasive grass species, Agrostis capillaris, on two co-occurring native
      New Zealand grasses, and vice versa. We explicitly separated above- and
      belowground interactions amongst these species experimentally and incorporated an
      N addition treatment. We found that competition with the invader had large
      negative impacts on native species growth (biomass decreased by half), resource
      capture (total N content decreased by up to 75%) and even nutrient stoichiometry
      (native species tissue C:N ratios increased). Surprisingly, these impacts were
      driven directly and indirectly by belowground competition, regardless of N
      availability. Higher root biomass likely enhanced the invasive grass's
      competitive superiority belowground, indicating that root traits may be useful
      tools for understanding invasive plant impacts. Our study shows that belowground
      competition can be more important in driving invasive plant impacts than
      aboveground competition in both low and high fertility ecosystems, including
      those experiencing N enrichment due to global change. This can help to improve
      predictions of how two key drivers of global change, plant species invasions and
      eutrophication, impact native species diversity.

PMID- 29218539
TI  - Carbon storage potential increases with increasing ratio of C4 to C3 grass cover
      and soil productivity in restored tallgrass prairies.
AB  - Long-term soil carbon (C) storage is essential for reducing CO2 in the
      atmosphere. Converting unproductive and environmentally sensitive agricultural
      lands to grasslands for bioenergy production may enhance C storage. However, a
      better understanding of the interacting effects of grass functional composition
      (i.e., relative abundance of C4 and C3 grass cover) and soil productivity on C
      storage will help guide sustainable grassland management. Our objective was to
      examine the relationship between grass functional composition and potential C
      storage and how it varies with potential soil productivity. We estimated C inputs
      from above- and belowground net primary productivity (ANPP and BNPP), and
      heterotrophic respiration (R H) to calculate net ecosystem production (NEP), a
      measure of potential soil C storage, in grassland plots of relatively high- and
      low-productivity soils spanning a gradient in the ratio of C4 to C3 grass cover
      (C4:C3). NEP increased with increasing C4:C3, but only in potentially productive
      soils. The positive relationship likely stemmed from increased ANPP, rather than
      BNPP, which was possibly related to efficient resource-use and
      physiological/anatomical advantages of C4 plants. R H was negatively correlated
      with C4:C3, possibly because of changes in microclimate or plant-microbe
      interactions. It is possible that in potentially productive soils, C storage can
      be enhanced by favoring C4 over C3 grasses through increased ANPP and BNPP and
      reduced R H. Results also suggest that potential C storage gains from C4
      productivity would not be undermined by a corresponding increase in R H.

PMID- 29218540
TI  - Corporate Philanthropy Toward Community Health Improvement in Manufacturing
      Communities.
AB  - Virtually all large employers engage in corporate philanthropy, but little is
      known about the extent to which it is directed toward improving community health.
      We conducted in-depth interviews with leaders of corporate philanthropy from 13
      of the largest manufacturing companies in the US to understand how giving
      decisions were made, the extent to which funding was directed towards improving
      community health, and whether companies coordinate with local public health
      agencies. We found that corporate giving was sizable and directed towards
      communities in which the manufacturers have a large presence. Giving was aligned
      with the social determinants of health (i.e., aimed at improving economic
      stability, the neighborhood and physical environment, education, food security
      and nutrition, the community and social context, and the health care system).
      However, improving public health was not often cited as a goal of corporate
      giving, and coordination with public health agencies was limited. Our results
      suggest that there may be opportunities for public health agencies to help guide
      corporate philanthropy, particularly by sharing community-level data and offering
      their measurement and evaluation expertise.

PMID- 29218541
TI  - Understanding Health, Violence, and Acculturation Among South Asian Women in the
      US.
AB  - The devastating effects of experiencing violence in childhood are seen well into
      adulthood. This has been particularly difficult to assess among South Asians
      living in the U.S., due to a lack of disaggregated data on this ethnic group. In
      a web-based survey administered to a convenience sample of South Asian women
      living in the U.S. (n = 535), information was gathered on experience/exposure to
      childhood violence; adult intimate partner violence; and adverse health outcomes,
      including ever suicide ideation/attempt, experiences of quality of life and body
      esteem in adulthood. Further, an individual's acculturation levels were measured
      specifically looking at cultural identity which was guided by Berry's
      biculturalism model. This study found that acculturation status is a key factor
      with respect to childhood verbal, physical, and sexual abuse, as well as body
      esteem and an individual's well-being. These results suggest that acculturation
      plays a key role for childhood violence, as well as key adult health indicators.
      The findings in this study, suggest that more research is warranted to better
      understand the complex relationships between acculturation status and health.
      While studies of South Asian immigrants have increased substantially, the study
      on how acculturation influences family violence and health outcomes has lagged
      behind. The findings in this study will provide guidance for future work in
      understanding how acculturation can play a key role in addressing the health and
      well-being of South Asian women in the U.S.

PMID- 29218542
TI  - Tracking Success: Outputs Versus Outcomes-A Comparison of Accredited and Non
      Accredited Public Health Agencies' Community Health Improvement Plan objectives.
AB  - With funding for public health initiatives declining, creating measurable
      objectives that are focused on tracking and changing population outcomes (i.e.,
      knowledge, attitudes, or behaviors), instead of those that are focused on health
      agencies' own outputs (e.g., promoting services, developing communication
      messages) have seen a renewed focus. This study analyzed 4094 objectives from the
      Community Health Improvement Plans (CHIPs) of 280 local PHAB-accredited and non
      accredited public health agencies across the United States. Results revealed that
      accredited agencies were no more successful at creating outcomes-focused
      objectives (35% of those coded) compared to non-accredited agencies (33% of those
      coded; Z = 1.35, p = .18). The majority of objectives were focused on outputs
      (accredited: 61.2%; non-accredited: 63.3%; Z = 0.72, p = .47). Outcomes-focused
      objectives primarily sought to change behaviors (accredited: 85.43%; non
      accredited: 80.6%), followed by changes in knowledge (accredited: 9.75%; non
      accredited: 10.8%) and attitudes (accredited: 1.6%; non-accredited: 5.1%). Non
      accredited agencies had more double-barreled objectives (49.9%) compared to
      accredited agencies (32%; Z = 11.43, p < .001). The authors recommend that
      accreditation procedures place a renewed focus on ensuring that public health
      agencies strive to achieve outcomes. It is also advocated that public health
      agencies work with interdisciplinary teams of Health Communicators who can help
      them develop procedures to effectively and efficiently measure outcomes of
      knowledge and attitudes that are influential drivers of behavioral changes.

PMID- 29218543
TI  - Does Studying 'Ethics' Improve Engineering Students' Meta-Moral Cognitive Skills?
AB  - This study examines the assumption that training in professional ethics is a
      predictor of the meta-moral cognitive ability of engineering students. The main
      purpose of the study was to check the difference in the meta-moral cognitive
      abilities between those students who studied a course on professional ethics, as
      part of the engineering curriculum, and those who did not undertake such a
      course. Using the survey method, the author conducted a pilot study amongst 243
      engineering undergraduates. The meta-moral cognitive awareness inventory
      developed on the basis of the meta-cognitive awareness inventory prepared by
      Schraw Gregory and Dennison Rayne Sperling was used to measure the meta-moral
      cognitive level of the respondents. The results show that there was a substantial
      difference in the meta-moral cognitive abilities between those students who
      studied professional ethics, and those who did not. The univariate analysis of
      variance of the collected data reveals a significant variance (p = .017).

PMID- 29218544
TI  - The Molecular Pathway Regulating Bergmann Glia and Folia Generation in the
      Cerebellum.
AB  - Evolution of complex behaviors in higher vertebrates and primates require the
      development of sophisticated neuronal circuitry and the expansion of brain
      surface area to accommodate the vast number of neuronal and glial populations. To
      achieve these goals, the neocortex in primates and the cerebellum in amniotes
      have developed specialized types of basal progenitors to aid the folding of their
      cortices. In the cerebellum, Bergmann glia constitute such a basal progenitor
      population, having a distinctive morphology and playing a critical role in
      cerebellar corticogenesis. Here, we review recent studies on the induction of
      Bergmann glia and their crucial role in mediating folding of the cerebellar
      cortex. These studies uncover a key function of FGF-ERK-ETV signaling cascade in
      the transformation of Bergmann glia from radial glia in the ventricular zone.
      Remarkably, in the neocortex, the same signaling axis operates to facilitate the
      transformation of ventricular radial glia into basal radial glia, a Bergmann glia
      like basal progenitor population, which have been implicated in the establishment
      of neocortical gyri. These new findings draw a striking similarity in the
      function and ontogeny of the two basal progenitor populations born in distinct
      brain compartments.

PMID- 29218545
TI  - A2B adenosine receptor agonist induces cell cycle arrest and apoptosis in breast
      cancer stem cells via ERK1/2 phosphorylation.
AB  - PURPOSE: It has been reported that cancer stem cells (CSCs) may play a crucial
      role in the development, recurrence and metastasis of breast cancer. Targeting
      signaling pathways in CSCs is considered to be a promising strategy for the
      treatment of cancer. Here, we investigated the role of the A2B adenosine receptor
      (A2BAR) and its associated signaling pathways in governing the proliferation and
      viability of breast cancer cell line derived CSCs. METHODS: CSCs were isolated
      from the breast cancer cell lines MCF-7 and MDA-MB-231 using a mammosphere assay.
      The effect of the A2BAR agonist BAY606583 on cell proliferation was evaluated
      using XTT and mammosphere formation assays, respectively. Apoptosis was assessed
      using Annexin-V staining and cell cycle analyses were performed using flow
      cytometry. The expression levels of Bax, Bcl-2, cyclin-D1, CDK-4 and
      (phosphorylated) ERK1/2 were assessed using Western blotting. RESULTS: Our data
      revealed that the breast cancer cell line derived mammospheres were enriched for
      CSCs. We also found that A2BAR stimulation with its agonist BAY606583 inhibited
      mammosphere formation and CSC viability. In addition, we found that the
      application of BAY606583 led to CSC cell cycle arrest and apoptosis through the
      cyclin-D1/Cdk-4 and Bax/Bcl-2 pathways, respectively. Notably, we found that
      BAY606583 significantly down-regulated ERK1/2 phosphorylation in the breast
      cancer cell line derived CSCs. CONCLUSIONS: From our results we conclude that
      A2BAR induces breast CSC cell cycle arrest and apoptosis through downregulation
      of the ERK1/2 cascade. As such, A2BAR may be considered as a novel target for the
      treatment of breast cancer.

PMID- 29218546
TI  - Establishing cut-off points with clinical relevance for bcl-2, cyclin D1, p16,
      p21, p27, p53, Sox11 and WT1 expression in glioblastoma - a short report.
AB  - PURPOSE: Glioblastoma (GBM) ranks among the most challenging cancers to treat and
      there is an urgent need for clinically relevant prognostic and diagnostic
      biomarkers. Here, we set out to investigate the expression of eight proteins (bcl
      2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1) in GBM with the specific aim to
      establish immunohistochemistry cut-off points with clinical relevance. METHODS:
      Immunohistochemistry (IHC) was used to examine protein expression in 55 surgical
      GBM specimens using H-scores, and IHC cut-off points were established using the
      Cutoff Finder web platform. Protein co-expression and its correlation with
      histopathological features were assessed, and cases were classified according to
      IDH1 mutation status. Survival curves were determined using Kaplan-Meier
      analyses. RESULTS: Clinical and molecular parameters found to be correlated with
      overall survival (OS) were tumor size (r = -0.278; p = 0.048), p53 (r = -0.452; p
      = 0.001), p16 (r = 0.351; p = 0.012) and Sox11 (r = 0.324; p = 0.020). In
      addition, we found that tumor size correlated with cyclin D1 (r = -0.282; p =
      0.037), p53 (r = 0.269; p = 0.041), Sox11 (r = -0.309; p = 0.022) and WT1 (r = 
      0.372; p = 0.003). Variables found to be significantly associated with IDH1
      mutation status were OS (p < 0.01), age (p < 0.01), cyclin D1 (p = 0.046), p16 (p
      = 0.019) and Sox11 (p = 0.012). Variables found to be significantly associated
      with a poor survival were tumor size >5 cm (p < 0.001), bcl-2 score > 40 (p =
      0.034), cyclin D1 score <= 70 (p = 0.004), p16 score <= 130 (p = 0.005), p53
      score > 20 (p = 0.003), Sox11 score <= 40 (p < 0.001) and WT1 score <= 270 (p =
      0.02). CONCLUSIONS: Correlations between protein biomarkers and main clinical GBM
      variables were identified. The establishment of distinct biomarker cut-off points
      may enable clinicians and pathologists to better weigh their prognostic value.

PMID- 29218548
TI  - From mesophilic to thermophilic conditions: one-step temperature increase
      improves the methane production of a granular sludge treating agroindustrial
      effluents.
AB  - OBJECTIVES: To assess the effect of one-step temperature increase, from 35 to 55 
      degrees C, on the methane production of a mesophilic granular sludge (MGS)
      treating wine vinasses and the effluent of a hydrogenogenic upflow anaerobic
      sludge blanket (UASB) reactor. RESULTS: One-step temperature increase from
      mesophilic to thermophilic conditions improved methane production regardless of
      the substrate tested. The biomethane potentials obtained under thermophilic
      conditions were 1.8-2.9 times higher than those obtained under mesophilic
      conditions. The MGS also performed better than an acclimated thermophilic
      digestate, producing 2.2-2.5 times more methane than the digestate under
      thermophilic conditions. Increasing the temperature from 35 to 55  degrees C also
      improved the methane production rate of the MGS (up to 9.4 times faster) and
      reduced the lag time (up to 1.9 times). Although the temperature increase
      mediated a decrease in the size of the sludge granules, no negative effects on
      the performance of the MGS was observed under thermophilic conditions.
      CONCLUSIONS: More methane is obtained from real agroindustrial effluents at
      thermophilic conditions than under mesophilic conditions. One-step temperature
      increase (instead of progressive sequential increases) can be used to implement
      the thermophilic anaerobic digestion processes with MGS.

PMID- 29218547
TI  - Expression of Class I Histone Deacetylases in Ipsilateral and Contralateral
      Hemispheres after the Focal Photothrombotic Infarction in the Mouse Brain.
AB  - Histone acetylation and deacetylation are among the most important epigenetic
      processes that regulate gene expression. Nonselective inhibitors of histone
      deacetylases (HDAC) can protect brain cells during ischemia and stroke. However,
      which HDAC isoform is involved in this effect is unknown. Some isoforms of
      histone deacetylases (HDACs) protect brain cells after ischemia, whereas others
      can promote their death. Most studies consider early periods (1-24 h) after
      stroke, whereas little is known on the involvement of HDACs during recovery after
      stroke. In this study, cellular and intracellular rearrangement of class I HDACs
      (HDAC1, HDAC2, HDAC3, HDAC8) was investigated at late periods after
      photothrombotic infarction (PTI) of the mouse sensorimotor cortex in intact
      tissue that surrounds the ischemia core, in the corresponding region of the
      contralateral hemisphere, and in the hippocampus. Each HDAC isoform had a
      specific pattern of expression and intracellular distribution in neurons and
      astrocytes at different periods after the ischemia. We did not observe ischemia
      induced changes in the subcellular localization of HDACs under study. Three days
      after the PTI, the expression of HDAC2 was increased in neurons of the damaged
      hemisphere. The activity of HDAC2 and HDAC8 was elevated 7 days after the
      ischemia both in neurons and astrocytes of the studied brain structures; the
      activity of HDAC8 was also increased 14 days after the ischemia. It is notable
      that the expression of class I HDACs in the intact hemisphere changes in the same
      way as their expression in the living tissue of the damaged hemisphere. HDAC1 was
      found both in the nuclei and cytoplasm of the brain cells; HDAC2 was
      predominantly localized in the nuclei, and HDAC8 was predominantly observed in
      the cytoplasm. This in addition to the regulation of gene transcription indicates
      nontranscriptional activity of HDAC1 and HDAC8 during recovery of the brain
      tissue after the ischemia. HDAC2 and HDAC8 were identified as potential mediators
      in an early recovery period after stroke, suggesting that selective inhibitors
      and activators of HDACs can be considered for therapeutic approaches in this
      period.

PMID- 29218549
TI  - Accuracy and reliability of a subcutaneous continuous glucose monitoring device
      in critically ill patients.
AB  - Subcutaneous continuous glucose monitoring (CGM) may have benefits in achieving
      glycemic control in critically ill patients. The aim of this study was to assess
      the accuracy and reliability of the FreeStyle Navigator I in critically ill
      patients and to assess patient related factors influencing the accuracy and
      reliability. This study is a retrospective analysis of data from a randomized
      controlled trial conducted in a 20-bed mixed intensive care unit. Analytical
      accuracy, clinical accuracy and reliability were assessed against arterial blood
      glucose samples as reference. Assessment was according to recent consensus
      recommendations with median absolute relative difference (median ARD), Bland
      Altman plots, the ISO system accuracy standards (ISO 15197:2013) and Clarke error
      grid analysis (CEG). We analyzed 2840 paired measurements from 155 critically ill
      patients. The median ARD of all paired values was 13.3 [6.9-22.1]%. The median
      ARD was significantly higher in both the hypoglycemic and the hyperglycemic range
      (32.4 [12.1-53.4]% and 18.7 [10.7-28.3]% respectively, p < 0.001). The Bland
      Altman analysis showed a mean bias of - 0.82 mmol/L with a lower limit of
      agreement (LOA) of - 3.88 mmol/L and an upper LOA of 2.24 mmol/L. A total of 1626
      (57.3%) values met the ISO-2013, standards and 1,334 (47%) CGM values were within
      12.5% from the reference value. CEG: 71.0% zone A, 25.8% zone B, 0.5% zone C,
      2.5% zone D, 0.3% zone E. The median overall real-time data display time was 94.0
      +/- 14.9% and in 23% of the patients, the sensor measured < 95% of the time.
      Additionally, data gaps longer than 30 min were found in 48% of the patients. The
      analytical accuracy of the FreeStyle Navigator I in critically ill patients was
      suboptimal. Furthermore, the clinical accuracy, did not meet the required
      standards. The reliability was satisfactory, however, in almost a quarter of the
      patients the realtime data display was < 95%. The accuracy was considerably and
      significantly lower in hyper- and hypoglycemic ranges.

PMID- 29218550
TI  - Small Angle Scattering: Historical Perspective and Future Outlook.
AB  - Small angle scattering (SAS) is a powerful and versatile tool to elucidate the
      structure of matter at the nanometer scale. Recently, the technique has seen a
      tremendous growth of applications in the field of structural molecular biology.
      Its origins however date back to almost a century ago and even though the methods
      potential for studying biological macromolecules was realized already early on,
      it was only during the last two decades that SAS gradually became a major
      experimental technique for the structural biologist. This rise in popularity and
      application was driven by the concurrence of different key factors such as the
      increased accessibility to high quality SAS instruments enabled by the growing
      number of synchrotron facilities and neutron sources established around the
      world, the emerging need of the structural biology community to study large multi
      domain complexes and flexible systems that are hard to crystalize, and in
      particular the development and availability of data analysis software together
      with the overall access to computational resources powerful enough to run them.
      Today, SAS is an established and widely used tool for structural studies on bio
      macromolecules. Given the potential offered by the next generation X-ray and
      neutron sources as well as the development of new, innovative approaches to
      collect and analyze solution scattering data, the application of SAS in the field
      of structural molecular biology will certainly continue to thrive in the years to
      come.

PMID- 29218551
TI  - Sample and Buffer Preparation for SAXS.
AB  - In this book chapter, a practical approach for conducting small angle X-ray
      scattering (SAXS) experiments is given. Our aim is to guide SAXS users through a
      three-step process of planning, preparing and performing a basic SAXS
      measurement. The minimal requirements necessary to prepare samples are described
      specifically for protein and other macromolecular samples in solution. We address
      the very important aspects in terms of sample characterization using additional
      techniques as well as the essential role of accurately subtracting background
      scattering contributions. At the end of the chapter some advice is given for
      trouble-shooting problems that may occur during the course of the SAXS
      measurements. Automated pipelines for data processing are described which are
      useful in allowing users to evaluate the quality of the data 'on the spot' and
      consequently react to events such as radiation damage, the presence of unwanted
      sample aggregates or miss-matched buffers.

PMID- 29218552
TI  - Considerations for Sample Preparation Using Size-Exclusion Chromatography for
      Home and Synchrotron Sources.
AB  - The success of a SAXS experiment for structural investigations depends on two
      precise measurements, the sample and the buffer background. Buffer matching
      between the sample and background can be achieved using dialysis methods but in
      biological SAXS of monodisperse systems, sample preparation is routinely being
      performed with size exclusion chromatography (SEC). SEC is the most reliable
      method for SAXS sample preparation as the method not only purifies the sample for
      SAXS but also almost guarantees ideal buffer matching. Here, I will highlight the
      use of SEC for SAXS sample preparation and demonstrate using example proteins
      that SEC purification does not always provide for ideal samples. Scrutiny of the
      SEC elution peak using quasi-elastic and multi-angle light scattering techniques
      can reveal hidden features (heterogeneity) of the sample that should be
      considered during SAXS data analysis. In some cases, sample heterogeneity can be
      controlled using a small molecule additive and I outline a simple additive
      screening method for sample preparation.

PMID- 29218553
TI  - How to Analyze and Present SAS Data for Publication.
AB  - SAS is a powerful technique to investigate oligomeric state and domain
      organization of macromolecules, e.g. proteins and nucleic acids, under
      physiological, functional and even time resolved conditions. However,
      reconstructing three dimensional structures from SAS data is inherently
      ambiguous, as no information about orientation and phase is available. In
      addition experimental artifacts such as radiation damage, concentration effects
      and incorrect background subtraction can hinder the interpretation of even lead
      to wrong results. In this chapter, explanations on how to analyze data and how to
      assess and minimize the influence of experimental artifacts on the data.
      Furthermore, guidelines on how to present the resulting data and models to
      demonstrate the data supports the conclusion being made and that it is not biased
      by artifacts, will be given.

PMID- 29218554
TI  - Designing and Performing Biological Solution Small-Angle Neutron Scattering
      Contrast Variation Experiments on Multi-component Assemblies.
AB  - Solution small-angle neutron scattering (SANS) combined with contrast variation
      provides information about the size and shape of individual components of a multi
      component biological assembly, as well as the spatial arrangements between the
      components. The large difference in the neutron scattering properties between
      hydrogen and deuterium is key to the method. Isotopic substitution of deuterium
      for some or all of the hydrogen in either the molecule or the solvent can greatly
      alter the scattering properties of the biological assembly, often with little or
      no change to its biochemical properties. Thus, SANS with contrast variation
      provides unique information not easily obtained using other experimental
      techniques.If used correctly, SANS with contrast variation is a powerful tool for
      determining the solution structure of multi-component biological assemblies. This
      chapter discusses the principles of SANS theory that are important for contrast
      variation, essential considerations for experiment design and execution, and the
      proper approach to data analysis and structure modeling. As sample quality is
      extremely important for a successful contrast variation experiment, sample issues
      that can affect the outcome of the experiment are discussed as well as procedures
      used to verify the sample quality. The described methodology is focused on two
      component biological complexes. However, examples of its use for multi-component
      assemblies are also discussed.

PMID- 29218555
TI  - SAS-Based Structural Modelling and Model Validation.
AB  - Small angle scattering of X-rays (SAXS) and neutrons (SANS) is a structural
      technique to study disordered systems with chaotic orientations of scattering
      inhomogeneities at low resolution. An important example of such systems are
      solutions of biological macromolecules. Rapid development in the methodology for
      solution scattering data interpretation and model building during the last two
      decades brought the analysis far beyond the determination of just few overall
      structural parameters (which was the only possibility in the past) and ensured
      SAS a firm position in the methods palette of the modern life sciences. The
      advances in the methodology include ab initio approaches for shape and domain
      structure restoration from scattering curves without a priori structural
      knowledge, classification and validation of the models, evaluation of potential
      ambiguity associated with the reconstruction. In rigid body and hybrid modelling
      approaches, solution scattering is synergistically used with other structural
      techniques utilizing the complementary information such as atomic models of the
      components, intramolecular contacts, subunits orientations etc. for the
      reconstruction of complex systems. The usual requirement of the sample
      monodispersity has been loosed recently and the technique can now address such
      systems as weakly bound oligomers and transient complexes. These state-of-the-art
      methods are described together with the examples of their applications and the
      possible ways of post-processing of the models.

PMID- 29218556
TI  - Structural Characterization of Highly Flexible Proteins by Small-Angle
      Scattering.
AB  - Intrinsically Disordered Proteins (IDPs) are fundamental actors of biological
      processes. Their inherent plasticity facilitates very specialized tasks in cell
      regulation and signalling, and their malfunction is linked to severe pathologies.
      Understanding the functional role of disorder requires the structural
      characterization of IDPs and the complexes they form. Small-angle Scattering of X
      rays (SAXS) and Neutrons (SANS) have notably contributed to this structural
      understanding. In this review we summarize the most relevant developments in the
      field of SAS studies of disordered proteins. Emphasis is given to ensemble
      methods and how SAS data can be combined with computational approaches or other
      biophysical information such as NMR. The unique capabilities of SAS enable its
      application to extremely challenging disordered systems such as low-complexity
      regions, amyloidogenic proteins and transient biomolecular complexes. This
      reinforces the fundamental role of SAS in the structural and dynamic
      characterization of this elusive family of proteins.

PMID- 29218557
TI  - What Can We Learn from Wide-Angle Solution Scattering?
AB  - Extending collection of x-ray solution scattering data into the wide-angle regime
      (WAXS) can provide information not readily extracted from small angle (SAXS)
      data. It is possible to accurately predict WAXS scattering on the basis of atomic
      coordinate sets and thus use it as a means of testing molecular models
      constructed on the basis of crystallography, molecular dynamics (MD), cryo
      electron microscopy or ab initio modeling. WAXS data may provide insights into
      the secondary, tertiary and quaternary structural organization of macromolecules.
      It can provide information on protein folding and unfolding beyond that
      attainable from SAXS data. It is particularly sensitive to structural
      fluctuations in macromolecules and can be used to generate information about the
      conformational make up of ensembles of structures co-existing in solution. Novel
      approaches to modeling of structural fluctuations can provide information on the
      spatial extent of large-scale structural fluctuations that are difficult to
      obtain by other means. Direct comparison with the results of MD simulations are
      becoming possible. Because it is particularly sensitive to small changes in
      structure and flexibility it provides unique capabilities for the screening of
      ligand libraries for detection of functional interactions. WAXS thereby provides
      an important extension of SAXS that can generate structural and dynamic
      information complementary to that obtainable by other biophysical techniques.

PMID- 29218558
TI  - SAS-Based Studies of Protein Fibrillation.
AB  - Protein fibrillation is associated with a number of fatal amyloid diseases (e.g.
      Alzheimer's and Parkinson's diseases). From a structural point of view, the
      aggregation process starts from an ensemble of native states that convert into
      transiently formed oligomers, higher order assemblies and protofibrils and,
      finally, fibrils. The different species exist in equilibrium in solution leading
      to a high degree of sample heterogeneity. It is impossible to physically isolate
      any single species for structural analysis: separation will alter the equilibrium
      and potentially cause structural changes.Small angle scattering is an optimal
      method for structural studies of the fibrillation process in order to further the
      knowledge of the associated diseases. The recorded scattering data include the
      scattering contribution of all the species in solution and must be decomposed to
      enable structural modeling of the individual components involved during the
      fibrillation, notably without physical separation of the species. In this chapter
      we explain how to optimize a small angle scattering analysis of the fibrillation
      process and the basic principles behind analysis of the data. We include several
      practical tips and highlight existing reports, exemplifying the wealth of
      information that can be derived from the method.

PMID- 29218559
TI  - High Resolution Distance Distributions Determined by X-Ray and Neutron
      Scattering.
AB  - Measuring distances within or between macromolecules is necessary to understand
      the chemistry that biological systems uniquely enable. In performing their
      chemistry, biological macromolecules undergo structural changes over distances
      ranging from atomic to micrometer scales. X-ray and neutron scattering provide
      three key assets for tackling this challenge. First, they may be conducted on
      solutions where the macromolecules are free to sample the conformations that
      enable their chemistry. Second, there are few limitations on chemical environment
      for experiments. Third, the techniques can inform upon a wide range of distances
      at once. Thus scattering, particularly recorded at small angles (SAS), has been
      applied to a large variety of phenomenon. A challenge in interpreting scattering
      data is that the desired three dimensional distance information is averaged onto
      one dimension. Furthermore, the scales and variety of phenomenon interrogated
      have led to an assortment of functions that describe distances and changes
      thereof. Here we review scattering studies that characterize biological
      phenomenon at distances ranging from atomic to 50 nm. We also distinguish the
      distance distribution functions that are commonly used to describe results from
      these systems. With available X-ray and neutron scattering facilities, bringing
      the action that occurs at the atomic to the micrometer scale is now reasonably
      accessible. Notably, the combined distance and dynamic information recorded by
      SAS is frequently key to connecting structure to biological activity and to
      improve macromolecular design strategies and outcomes. We anticipate widespread
      utilization particularly in macromolecular engineering and time-resolved studies
      where many contrasting experiments are necessary for resolving chemical
      mechanisms through structural changes.

PMID- 29218560
TI  - A Successful Combination: Coupling SE-HPLC with SAXS.
AB  - A monodispersed and ideal solution is a central (unique?) requirement of SAXS to
      allow one to extract structural information from the recorded pattern. On-line
      Size Exclusion Chromatography (SEC) marked a major breakthrough, separating
      particles present in solution according to their size. Identical frames under an
      elution peak can be averaged and further processed free from contamination.
      However, this is not always straightforward, separation is often incomplete and
      software have been developed to deconvolve the contributions from the different
      species (molecules or oligomeric forms) within the sample. In this chapter, we
      present the general workflow of a SEC-SAXS experiment. We present recent
      instrumental and data analysis improvements that have improved the quality of
      recorded data, extended its potential and turn it into a mainstream approach. We
      describe into some details two specific applications of SEC-SAXS that provide
      more than just separating associated forms from the particle of interest.

PMID- 29218561
TI  - Applications of SANS to Study Membrane Protein Systems.
AB  - Small angle neutron scattering (SANS) is a powerful tool to obtain structural
      information on solubilized membrane proteins on the nanometer length-scale in
      complement to other structural biology techniques such as cryo-EM, NMR and SAXS.
      In combination with deuteration of components and/or contrast variation (H2O:D2O
      exchange in the buffer) SANS allows to separate structural information from the
      protein and the detergent/lipid parts in solution. After a short historical
      overview on results obtained by SANS on membrane protein systems, this book
      chapter introduces the basic theoretical principles of the technique as well as
      requirements on samples. The two introductory sections are followed by an
      illustration of the specific consequences of sample heterogeneity of solubilized
      membrane proteins in the presence of detergent/lipid molecules on the
      interpretation of structural information by using simple, geometric models. The
      next sections deal with more sophisticated modelling approaches including ab
      initio shape reconstructions and full-atomic models in the presence of
      detergent/lipid and specific results obtained by these approaches. After a short
      comparison with the SAXS technique, this book chapter concludes with an overview
      of present and future developments and impact that can be expected by SANS on
      membrane structural biology in the coming years.

PMID- 29218562
TI  - Hybrid Applications of Solution Scattering to Aid Structural Biology.
AB  - Biomolecular applications of solution X-ray and neutron scattering (SAXS and
      SANS, respectively) started in late 1960s - early 1970s but were relatively
      limited in their ability to provide a detailed structural picture and lagged
      behind what became the two primary methods of experimental structural biology - X
      ray crystallography and NMR. However, improvements in both data analysis and
      instrumentation led to an explosive growth in the number of studies that used
      small-angle scattering (SAS) for investigation of macromolecular structure, often
      in combination with other biophysical techniques. Such hybrid applications are
      nowadays quickly becoming a norm whenever scattering data are used for two
      reasons. First, it is generally accepted that SAS data on their own cannot lead
      to a uniquely defined high-resolution structural model, creating a need for
      supplementing them with information from complementary techniques. Second,
      solution scattering data are frequently applied in situations when a method such
      NMR or X-ray crystallography cannot provide a satisfactory structural picture,
      which makes these additional restraints highly desirable. Maturation of the
      hybrid bio-SAS approaches brings to light new questions including completeness of
      the conformational space sampling, model validation, and data compatibility.

PMID- 29218563
TI  - A Practical Guide to iSPOT Modeling: An Integrative Structural Biology Platform.
AB  - Integrative structure modeling is an emerging method for structural determination
      of protein-protein complexes that are challenging for conventional structural
      techniques. Here, we provide a practical protocol for implementing our integrated
      iSPOT platform by integrating three different biophysical techniques: small-angle
      X-ray scattering (SAXS), hydroxyl radical footprinting, and computational docking
      simulations. Specifically, individual techniques are described from experimental
      and/or computational perspectives, and complementary structural information from
      these different techniques are integrated for accurate characterization of the
      structures of large protein-protein complexes.

PMID- 29218564
TI  - Small Angle Scattering for Pharmaceutical Applications: From Drugs to Drug
      Delivery Systems.
AB  - The sub-nanometer scale provided by small angle neutron and X-ray scattering is
      of special importance to pharmaceutical and biomedical investigators. As drug
      delivery devices become more functionalized and continue decreasing in size, the
      ability to elucidate details on size scales smaller than those available from
      optical techniques becomes extremely pertinent. Information gathered from small
      angle scattering therefore aids the endeavor of optimizing pharmaceutical
      efficacy at its most fundamental level. This chapter will provide some relevant
      examples of drug carrier technology and how small angle scattering (SAS) can be
      used to solve their mysteries. An emphasis on common first-step data treatments
      is provided which should help clarify the contents of scattering data to new
      researchers. Specific examples of pharmaceutically relevant research on novel
      systems and the role SAS plays in these studies will be discussed. This chapter
      provides an overview of the current applications of SAS in drug research and some
      practical considerations for selecting scattering techniques.

PMID- 29218565
TI  - Alliance and Treatment Outcome in Family-Involved Treatment for Youth Problems: A
      Three-Level Meta-analysis.
AB  - Alliance has been shown to predict treatment outcome in family-involved treatment
      for youth problems in several studies. However, meta-analytic research on
      alliance in family-involved treatment is scarce, and to date, no meta-analytic
      study on the alliance-outcome association in this field has paid attention to
      moderating variables. We included 28 studies reporting on the alliance-outcome
      association in 21 independent study samples of families receiving family-involved
      treatment for youth problems (N = 2126 families, M age youth ranging from 10.6 to
      16.1). We performed three multilevel meta-analyses of the associations between
      three types of alliance processes and treatment outcome, and of several moderator
      variables. The quality of the alliance was significantly associated with
      treatment outcome (r = .183, p < .001). Correlations were significantly stronger
      when alliance scores of different measurement moments were averaged or added,
      when families were help-seeking rather than receiving mandated care and when
      studies included younger children. The correlation between alliance improvement
      and treatment outcome just failed to reached significance (r = .281, p = .067),
      and no significant correlation was found between split alliances and treatment
      outcome (r = .106, p = .343). However, the number of included studies reporting
      on alliance change scores or split alliances was small. Our findings demonstrate
      that alliance plays a small but significant role in the effectiveness of family
      involved treatment. Future research should focus on investigating the more
      complex systemic aspects of alliance to gain fuller understanding of the dynamic
      role of alliance in working with families.

PMID- 29218566
TI  - Gastric neuroendocrine tumor arising from heterotopic pancreas.
AB  - There are few English reports on secondary tumors from heterotopic pancreas.
      Here, we describe a case of gastric neuroendocrine tumor (NET) arising from
      heterotopic pancreas. A 72-year-old woman underwent esophagogastroduodenoscopy as
      part of a general health check-up. An endoscopic examination revealed a
      submucosal tumor on the greater curvature of the gastric body. Laparoscopic and
      endoscopic cooperative surgery was performed. Histological diagnosis concluded
      that it was a Grade 1 NET arising from heterotopic pancreas. We report this
      extremely rare case of a NET presenting as a submucosal tumor, considered to have
      originated from heterotopic pancreatic tissue.

PMID- 29218568
TI  - Peer Education Group Intervention to Reduce Psychological Insulin Resistance: A
      Pilot Mixed-Method Study in a Chinese Population.
AB  - INTRODUCTION: Psychological insulin resistance (PIR) is common among type II
      diabetes (DM) patients. Although interventions to reduce PIR have been suggested,
      there is no standardized intervention to reduce PIR. This trial aimed to assess
      the preliminary effectiveness of a well-structured interventional patient group
      (for sample size calculation for larger trials), as well as the acceptability and
      feasibility of this intervention group. METHODS: This study used a quasi
      experimental, mixed-method approach. Fifty-three patients with DM were recruited
      to an interventional group that included a general education of DM and insulin,
      an insulin pen demonstration, and an insulin-using peer sharing session. Each
      group consisted of around 15 participants and lasted for 2 h each. The validated
      Chinese version of the insulin treatment appraisal scale (C-ITAS) was
      administered before, immediately after, and 1 month after the intervention to
      measure any changes in the participants' PIR. Patients were interviewed to assess
      the acceptability of the intervention until data saturation. RESULTS: Repeated
      measures ANOVA showed that the post-intervention C-ITAS scores (immediately post
      group and at 1 month) were lower than the pre-intervention C-ITAS scores (p <
      0.001). Changes in multiple attitudes toward insulin were detected before and
      after the group intervention. Ten patient interviews were conducted and found
      that the intervention was welcomed by all interviewees; no discomfort or adverse
      reactions were reported. CONCLUSION: Preliminary results showed that patient
      intervention groups with general education, insulin pen demonstration, and peer
      sharing appeared to be safe, acceptable, and effective in reducing PIR. Larger
      multicenter trials are needed to generalize these findings.

PMID- 29218569
TI  - Toxin positivity and tcdB gene load in broad-spectrum Clostridium difficile
      infection.
AB  - PURPOSE: This study aimed to evaluate the clinical significance of toxin
      positivity and toxin gene load, and the relation between them in the broad
      spectrum of Clostridium difficile infection (CDI) including colonization,
      significant diarrhea, and severe disease. METHODS: We included 2671 fecal samples
      submitted for CDI diagnosis and 180 samples from healthy individuals. The
      clinical spectrum was categorized as category I (toxigenic C. difficile positive
      without clinical CDI criteria), category II (mild CDI), and category III (severe
      CDI). Clinical parameters were compared based on toxin EIA and tcdB C t values. C
      t values of tcdB PCR for predicting toxin EIA positivity were assessed using
      receiver-operating characteristic (ROC) curves. RESULTS: The median C t values of
      tcdB PCR and toxin positivity were not significantly correlated with clinical
      spectrum of CDI (27.5, 28.2, and 26.1 for tcdB C t and 55.0, 56.6, and 60.9% for
      toxin EIA positivity in category I, II, and III, respectively, P > 0.05). There
      were significant differences in the tcdB C t values between toxin EIA-positive
      and -negative groups (P < 0.001). Optimal cutoff for the tcdB C t value for
      estimating toxin EIA positivity was 26.3 with 79.3% sensitivity and 83.6%
      specificity with good area under the curves (AUC, 0.848). CONCLUSIONS: The C t
      values successfully predicted toxin EIA positivity and could be used as a
      surrogate for toxin EIA positivity in the diagnostic algorithm and routine
      analysis. Further studies are needed to validate the clinical significance of
      tcdB PCR C t value in toxigenic C. difficile colonization and infection.

PMID- 29218570
TI  - Pure correlates of exploration and exploitation in the human brain.
AB  - Balancing exploration and exploitation is a fundamental problem in reinforcement
      learning. Previous neuroimaging studies of the exploration-exploitation dilemma
      could not completely disentangle these two processes, making it difficult to
      unambiguously identify their neural signatures. We overcome this problem using a
      task in which subjects can either observe (pure exploration) or bet (pure
      exploitation). Insula and dorsal anterior cingulate cortex showed significantly
      greater activity on observe trials compared to bet trials, suggesting that these
      regions play a role in driving exploration. A model-based analysis of task
      performance suggested that subjects chose to observe until a critical evidence
      threshold was reached. We observed a neural signature of this evidence
      accumulation process in the ventromedial prefrontal cortex. These findings
      support theories positing an important role for anterior cingulate cortex in
      exploration, while also providing a new perspective on the roles of insula and
      ventromedial prefrontal cortex.

PMID- 29218571
TI  - Culturable Endophytic Bacteria of Ginger Rhizome and their Remarkable Multi-trait
      Plant Growth-Promoting Features.
AB  - Functional contribution of endophytic bacteria towards plant growth is highly
      impressive due to their species diversity and array of probiotic mechanisms. In
      the study, 96 endophytic bacteria isolated from rhizome of ginger (Zingiber
      officinale) were screened for phosphate solubilisation, 1-amino cyclopropane-1
      carboxylate (ACC) deaminase activity, nitrogen fixation, ammonia and IAA
      production. Among these, sixteen endophytes with multiple plant growth-promoting
      activities were identified by 16S rDNA sequencing and all of them showed growth
      enhancement in Vigna unguiculata var Lola which make the study remarkably
      significant. The result was a clear indication of consistent, reliable and broad
      spectrum plant probiotic features of all the selected isolates. However, strain
      specific effects on soil parameters represent the unique and distinguishable role
      of each of the selected isolates in the chemobiology of ginger rhizome. The study
      provided deeper insight into microbiomics of ginger rhizome with its agricultural
      promises.

PMID- 29218572
TI  - Complete genome sequence of a new strain of Lagenaria siceraria endornavirus from
      China.
AB  - An RNA virus tentatively named Lagenaria siceraria endornavirus-Hubei (LsEV-HuB)
      was isolated from Lagenaria siceraria var. hispida in Hubei, China. The LsEV-HuB
      genome consists of 15,098 bp and contains a single open reading frame (ORF)
      encoding a large protein with several conserved domains, including one helicase
      domain, one glycosyltransferase domain, two capsular polysaccharide synthesis
      protein (CPS) domains, and one RNA-dependent RNA polymerase (RdRp) domain. LsEV
      HuB has nucleotide and amino acid sequence identities of 72.96% and 77.95%,
      respectively, to Lagenaria siceraria endornavirus-California (LsEV-CA), the
      closest relative of LsEV-HuB.

PMID- 29218573
TI  - Dual neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus
      induced septic arthritis correlating alteration in the level of interferon gamma
      and interleukin-10 in terms of TNFR2 blocking.
AB  - Severity of S. aureus septic arthritis is correlated to prolonged inflammation by
      inflammatory cytokines like TNF-alpha, IL-1beta, and IL-6 even after successful
      elimination of bacteria. Role of TNF-alpha via TNFR2 is not well established in
      this aspect. IFN-gamma induces TNF-alpha release from the macrophages augmenting
      the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory
      cytokines promoting resolution of inflammation. TNF-alpha-TNFR2 signaling
      upregulates both of these cytokines. Higher level of MMP-2 induction by
      inflammatory cytokines during arthritis promotes tissue destruction. Whether dual
      neutralization of TNFR-2 and MMP-2 regulates the severity of S. aureus arthritis
      by modulating local and systemic cytokine milieu mainly due to TNFR-2 blocking
      was an obvious question. Here, we attempted the effects of neutralization of MMP
      2 and TNFR2 on S. aureus arthritis and its impact on pro-inflammatory cytokines
      and some other parameters related to tissue destruction. Reduction in arthritis
      index was noticed in infected mice treated with both MMP-2 inhibitor and TNFR2
      antibody. Lowest levels of inflammatory cytokines, iNOS, RANKL, NF-kappab, JNK
      kinase, ROS, and MPO, and lysozyme activity were observed in combined
      neutralization group at 9 and 15 dpi, but at 3 dpi, most of the above parameters
      remained elevated due to TNFR2 neutralization. Diminished IL-10 and IFN-gamma
      levels as a result of TNFR2 neutralization at early and later phase of infection
      respectively might be responsible for these contrasting effects. Overall, it can
      be suggested that administration of MMP-2 inhibitor and TNFR2 antibody in
      combination is protective against the inflammation and tissue destruction
      associated with S. aureus infection during the arthritic episode.

PMID- 29218574
TI  - Tracking long-distance atmospheric deposition of trace metal emissions from
      smelters in the upper Columbia River valley using Pb isotope analysis of lake
      sediments.
AB  - Heavy metal discharge from mining and smelting operations into aquatic ecosystems
      can cause long-term biological and ecological impacts. The upper Columbia River
      is highly contaminated with heavy metal wastes from nearby smelting operations in
      Trail, British Columbia, Canada, and to a lesser extent, Northport (Le Roi
      smelter), Washington, USA. Airborne emissions from the Trail operations were
      historically and are currently transported by prevailing winds down the Columbia
      River canyon, where particulate metals can be deposited into lakes and
      watersheds. In lakes, sediment cores contain records of past environmental
      conditions, providing a timeline of fundamental chemical and biological
      relationships within aquatic ecosystems, including records of airborne metal
      depositions. We analyzed trace metal concentrations (Ni, Cd, Zn, As, Cu, Sb, Pb,
      Hg) and Pb isotope compositions of sediment cores from six remote eastern
      Washington lakes to assess potential sources of atmospheric heavy metal
      deposition. Sediment cores displayed evidence to support trace metal loading as a
      direct consequence of smelting operations in Trail. Smelter contamination was
      detected 144 km downwind of the Trail Smelter. Cd, Sb, Pb (p < 0.001), and to a
      lesser extent As and Hg (p < 0.05) concentrations were correlated with Pb isotope
      compositions, suggesting that the Trail operations were likely the main source
      for these trace metals.

PMID- 29218575
TI  - Flow evaluation of the leaching hazardous materials from spent nickel-cadmium
      batteries discarded in different water surroundings.
AB  - The leaching characteristics of hazardous materials from Ni-Cd batteries immersed
      in four typical water samples, i.e., water with NaCl, river water, tap water, and
      deionized water, were investigated to evaluate the potential environmental harm
      of spent Ni-Cd batteries in the water surroundings. It is shown that four water
      surroundings all could leach hazardous materials from the Ni-Cd batteries. The
      water with NaCl concentration of 66.7 mg L-1 had the highest leaching ability,
      the hazardous materials were leached after only approximately 50 days (average
      time, with a standard deviation of 4.1), while less than 100 days were needed in
      the others. An electrochemical corrosion is considered to be the main leaching
      mechanism leading to battery breakage, while the dissolution-deposition process
      and the powder route result in the leakage and transference of nickel and cadmium
      materials from the electrodes. The anions, i.e., SO42- and Cl-, and dissolved
      oxygen in water were demonstrated to be the vital factors that influence the
      leaching processes. Thus, it is proposed that spent Ni-Cd batteries must be
      treated properly to avoid potential danger to the environment.

PMID- 29218576
TI  - MOF/graphene oxide composite as an efficient adsorbent for the removal of organic
      dyes from aqueous solution.
AB  - The metal-organic frameworks (MOFs) MIL-100(Fe) and graphene oxide (GO)
      composites were prepared by hydrothermal method and characterized by X-ray
      diffraction (XRD), nitrogen adsorption/desorption, thermal-gravimetric (TG)
      analysis, the Fourier Transform Infrared Spectroscopy (FTIR), and scanning
      electron microscopy (SEM). The composites were used for the adsorption of
      methylene blue (MB) and methyl orange (MO) in aqueous solution. The results
      indicated that MIL-100(Fe) and GO formed a sandwich-like structure, and the
      crystal structure of MIL-100(Fe) was reserved in the composites. The attachment
      of GO layers to the MIL-100(Fe) decreased the surface area from 1690 to 1602
      m2/g, and pore volume from 0.996 to 0.770 cm3/g when 5% (w/w) GO was added, due
      to the coating of MIL-100(Fe) by GO sheets. The addition of 5% (w/w) GO increased
      the adsorption capacity for MB (from 1019 to 1231 mg/g) and MO (from 667 to 1189
      mg/g). The composites showed a better thermal stability than MIL-100(Fe); the
      decomposition temperature increased from 280 to 350  degrees C. The addition of
      GO improved the properties of MIL-100(Fe) as an adsorbent for MO/MB from aqueous
      solution.

PMID- 29218577
TI  - Street foods exacerbate effects of the environmental burden of polycyclic
      aromatic hydrocarbons (PAHs) in Nigeria.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a large group of well-known toxicants
      with carcinogenic potential and other health effects including on the immune
      system. The high health risks of non-communicable diseases and relevant
      comorbidities in Africa, particularly in contaminated areas like e-waste and
      crude oil and gas exploration areas and for high consumers of food commodity
      groupings which are most critical for PAH exposure, are exacerbated by dietary
      exposure due to unsafe practices in commonly consumed foods, like those street
      vended.In February 2016, 20 commonly consumed street foods were purchased
      directly from vendors at major bus stops in Benin City and Umunede in Nigeria.
      The concentration of 16 priority PAHs was determined. The dietary intake of
      B[a]P, ?PAH, PAH4, PAH8, and ?B(a)Peq was estimated for children, peripubertal
      children/adolescent, and adult using the total diet study (TDS) method. Among the
      analyzed PAHs, there was a predominance of chrysene (17.42 MUg/kg). Roasted yam
      (14.15 MUg/kg) and fried fish (1.40 MUg/kg) had the highest levels of ?PAH and
      B[a]P, respectively. The mean concentration of B[a]P, ?PAH, PAH4, PAH8, and
      ?B(a)Peq ranged from 0.65-1.40 MUg/kg, 0.20-14.15 MUg/kg, 0.43-5.22 MUg/kg, 0.13
      7.88 MUg/kg, and 0.002-2.123 MUg/kg, respectively. The mean concentration of
      B[a]P and PAH4 reported in this study was below the maximum allowable levels of 5
      and 12 MUg/kg for adults and above the maximum levels for young children set at
      1.0 MUg/kg for both B[a]P and PAH4 in food. The estimated dietary intake of
      B[a]P, ?PAH, PAH4, PAH8, and ?B(a)Peq for adult, adolescent, and children was
      0.56, 0.37, and 0.31 MUg/day; 17.6, 10.7, and 8.81 MUg/day; 5.78, 4.01, and 3.26
      MUg/day; 9.22, 6.19, and 5.09 MUg/day; and 1.72, 0.97, and 0.82 MUg/day,
      respectively.Street foods represent one important source of PAHs. The exposure
      occurring through street food compounds with that from home-made foods,
      environmental pollution, and lifestyle (tobacco smoke) is making up an aggregate
      daily exposure in the general population.The incremental lifetime cancer risk for
      adults and children from the consumption of street food was 7.6 * 10-8 and 2.1 *
      10-8, respectively. Along with initiatives to manage environmental contamination
      and promote healthier lifestyle, people should be empowered on healthy cooking
      practices and safe food cookery environments.

PMID- 29218578
TI  - Biomimetic synthesis of silver nanoparticles using flower extract of Bauhinia
      purpurea and its antibacterial activity against clinical pathogens.
AB  - In the present study, we have reported an eco-friendly, rapid, and simple method
      for the synthesis of silver nanoparticles (AgNPs) using Bauhinia purpurea flower
      extract as non-toxic bioreducing agent. The formation of AgNPs was confirmed by
      UV-visible spectroscopy, transmission electron microscopy (TEM), scanning
      electron microscopy and energy-dispersive spectroscopy (SEM-EDS), Fourier
      transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). The
      synthesized AgNPs were spherical in shape with an average size of 20 nm.
      Furthermore, the antibacterial activities of the synthesized AgNPs (2-10 mM)
      against clinical pathogens, Klebsiella sp. and Staphylococcus sp., were evaluated
      under in vitro conditions.

PMID- 29218579
TI  - Assessment of debris inputs from land into the river in the Three Gorges
      Reservoir Area, China.
AB  - Riverine debris in the Three Gorges Reservoir Area (TGRA) poses a threat to
      electricity generation, ship navigation, and water environment. Quantifying
      riverine debris inputs from land into the river is a foundation for modeling of
      the transport and accumulation of floating debris on the water surface in the
      TGRA. However, this has not been researched to date. In this study, debris inputs
      from land into the river in the TGRA were assessed according to the response
      relationship between debris inputs and surface runoff. The land-based debris
      inputs in the TGRA were estimated using simulated surface runoff which was
      simulated by the Soil and Water Assessment Tool (SWAT) model. Results showed that
      15.32 * 106 kg of land-based debris was inputted into the main channel of the
      TGRA in 2015 which accounted for 9.74% of total debris inputs (the monitoring
      data of river-sourced and land-sourced debris inputs was 157.27 * 106 kg). Debris
      inputs varied seasonally and peaked in the summer season (July to September).
      Compared with monthly measured data, the average relative errors in 2015 were
      below 30%. In addition, areas with higher debris pollution inputs were mainly
      located in the upper section of the TGRA, between the Tang River Basin and the
      Long River Basin. The proposed method was tested and determined to be reliable;
      thus, it can be used to quickly estimate debris inputs from land into the river
      by surface runoff of the outlets in a river basin. Moreover, this method provides
      new insight into the estimation of land-based debris inputs into rivers.

PMID- 29218580
TI  - Potential vulnerability of oak forests to climate change-induced flooding:
      effects of mild oxygen deficiency on Quercus robur and Quercus petraea seedling
      physiology.
AB  - Flooding is characterized by saturation of soil pores with water, leading to
      hypoxic conditions which affect plant root development and metabolism. We
      investigated the oxygen deficiency tolerance observed in Quercus robur and
      Quercus petraea and seek to understand whether it can be explained by enhanced
      efficiency in oxygen use in the roots, as estimated through radial oxygen loss
      visualization in relation to growth measurements and root apex respiration. The
      study showed that root growth, under oxygen deficiency conditions, was
      significantly reduced only in Q. robur seedlings. Root respiration was maintained
      in Q. robur, whereas it was decreased in Q. petraea. Both species set up a
      barrier against radial oxygen loss, though measurement of apex oxygen leakage
      showed greater oxygen efficiency in Q. robur seedlings. This strategy might allow
      Q. robur to maintain its respiration and thus to survive longer under oxygen
      deficiency conditions by facilitating the seedling establishment in transient
      flooded soils.

PMID- 29218581
TI  - Fabrication of Tip-Dissolving Microneedles for Transdermal Drug Delivery of
      Meloxicam.
AB  - Dissolving microneedles (MNs) offered a simple, minimally invasive method for
      meloxicam (MX) delivery to the skin. However, the fabrication of dissolving MNs
      still faced some challenges, such as significant time consumption, loss of drug
      activity, and difficulty in regulating MN drug loading. To address these issues,
      we developed the tip-dissolving (TD) MNs. Several kinds of drugs were
      encapsulated successfully, and the quantity of MX ranged from 37.23 +/- 8.40 to
      332.53 +/- 13.37 MUg was precisely controlled. The effects of fabrication process
      on biomacromolecules stability were studied, and it was found that tyrosinase
      kept 90.4% activity during the fabrication process. The whole process for the
      fabrication of MNs only takes approximately 1 h. In order to further evaluate the
      potential of the TD MNs, MX TD MNs were prepared for in vitro release
      experiments, in vivo release experiments, safety evaluation, pharmacokinetic
      studies, and pharmacodynamic studies. The results demonstrated that MX TD MNs
      offered several advantages, including rapid release of the encapsulated drug
      (91.72% within 30 min), efficient drug delivery to skin (79.18%), no obvious skin
      irritation, decent relative bioavailability (122.3%), and strong anti
      inflammatory and analgesic effects. Based on these results, we envisage that the
      TD MNs have promising potential for transdermal drug delivery of MX.

PMID- 29218582
TI  - Application of Fluorescence Emission for Characterization of Albendazole and
      Ricobendazole Micellar Systems: Elucidation of the Molecular Mechanism of Drug
      Solubilization Process.
AB  - Albendazole (ABZ) and ricobendazole (RBZ) are referred to as class II compounds
      in the Biopharmaceutical Classification System. These drugs exhibit poor
      solubility, which profoundly affects their oral bioavailability. Micellar systems
      are excellent pharmaceutical tools to enhance solubilization and absorption of
      poorly soluble compounds. Polysorbate 80 (P80), poloxamer 407 (P407), sodium
      cholate (Na-C), and sodium deoxycholate (Na-DC) have been selected as surfactants
      to study the solubilization process of these drugs. Fluorescence emission was
      applied in order to obtain surfactant/fluorophore (S/F) ratio, critical micellar
      concentration, protection efficiency of micelles, and thermodynamic parameters.
      Systems were characterized by their size and zeta potential. A blue shift from
      350 to 345 nm was observed when ABZ was included in P80, Na-DC, and Na-C
      micelles, while RBZ showed a slight change in the fluorescence band. P80 showed a
      significant solubilization capacity: S/F values were 688 for ABZ at pH 4 and 656
      for RBZ at pH 6. Additionally, P80 micellar systems presented the smallest size
      (10 nm) and their size was not affected by pH change. S/F ratio for bile salts
      was tenfold higher than for the other surfactants. Quenching plots were linear
      and their constant values (2.17/M for ABZ and 2.29/M for RBZ) decreased with the
      addition of the surfactants, indicating a protective effect of the micelles. Na
      DC showed better protective efficacy for ABZ and RBZ than the other surfactants
      (constant values 0.54 and 1.57/M, respectively), showing the drug inclusion into
      the micelles. Entropic parameters were negative in agreement with micelle
      formation.

PMID- 29218583
TI  - Promising Antibacterial Effects of Silver Nanoparticle-Loaded Tea Tree Oil
      Nanoemulsion: a Synergistic Combination Against Resistance Threat.
AB  - Highly resistant pathogens may be developed in patients with immune disorders
      after prolonged exposure to antibiotics, a growing threat worldwide. In order to
      overcome these problems, this study introduces a new class of engineered
      nanosystems comprising of tea tree oil nanoemulsion (TTO NE) loaded with Ag
      nanoparticles (NPs). Silver shows a strong toxicity towards a wide range of
      microorganisms. Also, TTO NE could be employed as a promising and safe
      antimicrobial agent for local therapies of bacterial infections. The nanosystem
      was prepared by low-energy method. Mean droplet size of the NE was found to be
      17.7 nm. Results of the antibacterial assays showed promising ability of the
      designed nanosystem for eradication of Gram-positive and Gram-negative bacteria
      (95%). Also, it was shown that introducing colloidal Ag NPs to the TTO NE exerted
      a synergistic effect against Escherichia coli (FIC 0.48) while only an additive
      effect was observed against Staphylococcus aureus (FIC 0.75). The antibacterial
      effects of TTO NE+Ag NPs together with their compatibility with human cells can
      present them as a suitable candidate to fight against the antibacterial
      resistance threat.

PMID- 29218584
TI  - Trajectory analysis of discrete goal-directed pointing movements: How many trials
      are needed for reliable data?
AB  - A powerful tool in motor behavior research is trajectory analysis of discrete
      goal-directed pointing movements. The purpose of the present analysis was to
      estimate the minimum number of trials per participant required to achieve the
      conventional level of reliability for trajectory analysis. We analyzed basic
      measurements of movement and three common methods of trajectory analysis within
      the framework of generalizability theory. Generalizability studies were used to
      decompose the total variance of these variables into the percent contributions
      from person, trial, and the person-by-trial interaction. Decision studies were
      then used to determine the minimum number of trials required to achieve the
      conventional level of reliability. The number of trials per participant needed
      for reliable data of discrete goal-directed pointing movements depended on the
      dependent variable-for example, reaction times required six or ten trials,
      movement times required three trials, and constant error required 47 trials. For
      trajectory analysis, ten or fewer trials were required for reliable dependent
      variables during the first half of the movement (up to peak velocity or 70% of
      the displacement). The number of trials required for the second half of the
      movement rapidly increased to 47 trials at movement termination. This increase in
      the number of trials required for reliable analysis of the second half of the
      movement was indicative of online control. Finally, correlation analysis was
      performed with simulated correlations on subsets of trials, and all 32 trials
      were required. However, 18 trials might be used without a practically significant
      change in the correlations.

PMID- 29218585
TI  - Analyzing the kinematics of hand movements in catching tasks-An online correction
      analysis of movement toward the target's trajectory.
AB  - Free, 3-D interceptive movements are difficult to visualize and quantify. For
      ball catching, the endpoint of a movement can be anywhere along the target's
      trajectory. Furthermore, the hand may already have begun to move before the
      subject has estimated the target's trajectory, and the subject may alter the
      targeted position during the initial part of the movement. We introduce a method
      to deal with these difficulties and to quantify three movement phases involved in
      catching: the initial, non-goal-directed phase; the goal-directed phase, which is
      smoothly directed toward the target's trajectory; and the final, interception
      phase. Therefore, the 3-D movement of the hand was decomposed into a component
      toward the target's trajectory (the minimal distance of the hand to the target's
      parabolic [MDHP] trajectory) and a component along this trajectory. To identify
      the goal-directed phase of the MDHP trajectory, we employed the empirical finding
      that goal-directed trajectories are minimally jerky. The second component, along
      the target's trajectory, was used to analyze the interaction of the hand with the
      ball. The method was applied to two conditions of a ball-catching task. In the
      manipulated condition, the initial part of the ball's flight was occluded, so the
      visibility of the ball was postponed. As expected, the onset of the smooth part
      of the movement shifted to a later time. This method can be used to quantify
      anticipatory behavior in interceptive tasks, allowing researchers to gain new
      insights into movement planning toward the target's trajectory.

PMID- 29218586
TI  - Nonparametric tests for equality of psychometric functions.
AB  - Many empirical studies measure psychometric functions (curves describing how
      observers' performance varies with stimulus magnitude) because these functions
      capture the effects of experimental conditions. To assess these effects,
      parametric curves are often fitted to the data and comparisons are carried out by
      testing for equality of mean parameter estimates across conditions. This approach
      is parametric and, thus, vulnerable to violations of the implied assumptions.
      Furthermore, testing for equality of means of parameters may be misleading:
      Psychometric functions may vary meaningfully across conditions on an observer-by
      observer basis with no effect on the mean values of the estimated parameters.
      Alternative approaches to assess equality of psychometric functions per se are
      thus needed. This paper compares three nonparametric tests that are applicable in
      all situations of interest: The existing generalized Mantel-Haenszel test, a
      generalization of the Berry-Mielke test that was developed here, and a split
      variant of the generalized Mantel-Haenszel test also developed here. Their
      statistical properties (accuracy and power) are studied via simulation and the
      results show that all tests are indistinguishable as to accuracy but they differ
      non-uniformly as to power. Empirical use of the tests is illustrated via analyses
      of published data sets and practical recommendations are given. The computer code
      in MATLAB and R to conduct these tests is available as Electronic Supplemental
      Material.

PMID- 29218587
TI  - Facial expression analysis with AFFDEX and FACET: A validation study.
AB  - The goal of this study was to validate AFFDEX and FACET, two algorithms
      classifying emotions from facial expressions, in iMotions's software suite. In
      Study 1, pictures of standardized emotional facial expressions from three
      databases, the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP), the
      Amsterdam Dynamic Facial Expression Set (ADFES), and the Radboud Faces Database
      (RaFD), were classified with both modules. Accuracy (Matching Scores) was
      computed to assess and compare the classification quality. Results show a large
      variance in accuracy across emotions and databases, with a performance advantage
      for FACET over AFFDEX. In Study 2, 110 participants' facial expressions were
      measured while being exposed to emotionally evocative pictures from the
      International Affective Picture System (IAPS), the Geneva Affective Picture
      Database (GAPED) and the Radboud Faces Database (RaFD). Accuracy again differed
      for distinct emotions, and FACET performed better. Overall, iMotions can achieve
      acceptable accuracy for standardized pictures of prototypical (vs. natural)
      facial expressions, but performs worse for more natural facial expressions. We
      discuss potential sources for limited validity and suggest research directions in
      the broader context of emotion research.

PMID- 29218588
TI  - Threats to the validity of eye-movement research in psychology.
AB  - Eyetracking research in psychology has grown exponentially over the past decades,
      as equipment has become cheaper and easier to use. The surge in eyetracking
      research has not, however, been equaled by a growth in methodological awareness,
      and practices that are best avoided have become commonplace. We describe nine
      threats to the validity of eyetracking research and provide, whenever possible,
      advice on how to avoid or mitigate these challenges. These threats concern both
      internal and external validity and relate to the design of eyetracking studies,
      to data preprocessing, to data analysis, and to the interpretation of eyetracking
      data.

PMID- 29218589
TI  - StimulStat: A lexical database for Russian.
AB  - In this article, we present StimulStat - a lexical database for the Russian
      language in the form of a web application. The database contains more than 52,000
      of the most frequent Russian lemmas and more than 1.7 million word forms derived
      from them. These lemmas and forms are characterized according to more than 70
      properties that were demonstrated to be relevant for psycholinguistic research,
      including frequency, length, phonological and grammatical properties,
      orthographic and phonological neighborhood frequency and size, grammatical
      ambiguity, homonymy and polysemy. Some properties were retrieved from various
      dictionaries and are presented collectively in a searchable form for the first
      time, the others were computed specifically for the database. The database can be
      accessed freely at http://stimul.cognitivestudies.ru .

PMID- 29218590
TI  - Measuring and testing the agreement of matrices.
AB  - The problem of comparing the agreement of two n * n matrices has a variety of
      applications in experimental psychology. A well-known index of agreement is based
      on the sum of the element-wise products of the matrices. Although less familiar
      to many researchers, measures of agreement based on within-row and/or within
      column gradients can also be useful. We provide a suite of MATLAB programs for
      computing agreement indices and performing matrix permutation tests of those
      indices. Programs for computing exact p-values are available for small matrices,
      whereas resampling programs for approximate p-values are provided for larger
      matrices.

PMID- 29218592
TI  - Mathematical Modeling of the Effects of Tumor Heterogeneity on the Efficiency of
      Radiation Treatment Schedule.
AB  - Radiotherapy uses high doses of energy to eradicate cancer cells and control
      tumors. Various treatment schedules have been developed and tried in clinical
      trials, yet significant obstacles remain to improving the radiotherapy
      fractionation. Genetic and non-genetic cellular diversity within tumors can lead
      to different radiosensitivity among cancer cells that can affect radiation
      treatment outcome. We propose a minimal mathematical model to study the effect of
      tumor heterogeneity and repair in different radiation treatment schedules. We
      perform stochastic and deterministic simulations to estimate model parameters
      using available experimental data. Our results suggest that gross tumor volume
      reduction is insufficient to control the disease if a fraction of radioresistant
      cells survives therapy. If cure cannot be achieved, protocols should balance
      volume reduction with minimal selection for radioresistant cells. We show that
      the most efficient treatment schedule is dependent on biology and model parameter
      values and, therefore, emphasize the need for careful tumor-specific model
      calibration before clinically actionable conclusions can be drawn.

PMID- 29218593
TI  - [Colonic stent as bridge to surgery versus emergency resection in patients with
      malignant colonic stenosis].

PMID- 29218591
TI  - Model-Based Phenotypic Signatures Governing the Dynamics of the Stem and Semi
      differentiated Cell Populations in Dysplastic Colonic Crypts.
AB  - Mathematical modeling of cell differentiated in colonic crypts can contribute to
      a better understanding of basic mechanisms underlying colonic tissue
      organization, but also its deregulation during carcinogenesis and tumor
      progression. Here, we combined bifurcation analysis to assess the effect that
      time delay has in the complex interplay of stem cells and semi-differentiated
      cells at the niche of colonic crypts, and systematic model perturbation and
      simulation to find model-based phenotypes linked to cancer progression. The
      models suggest that stem cell and semi-differentiated cell population dynamics in
      colonic crypts can display chaotic behavior. In addition, we found that clinical
      profiling of colorectal cancer correlates with the in silico phenotypes proposed
      by the mathematical model. Further, potential therapeutic targets for
      chemotherapy resistant phenotypes are proposed, which in any case will require
      experimental validation.

PMID- 29218594
TI  - [Adrenal carcinoma with vena cava thrombus].

PMID- 29218595
TI  - Quantitative Testing of Prescriber Knowledge Regarding the Risks and Safe Use of
      Albiglutide.
AB  - BACKGROUND: The risk of pancreatitis and potential risk of medullary thyroid
      carcinoma associated with glucagon-like peptide-1 receptor agonists prompted the
      US Food and Drug Administration to require a Risk Evaluation and Mitigation
      Strategy for albiglutide, including education for prescribers and subsequent
      assessment of their knowledge of the risks and safe use of albiglutide via a
      quantitative survey. OBJECTIVE: The objective of this study was to assess
      prescribers' knowledge of the risks related to medullary thyroid carcinoma,
      pancreatitis, and the appropriate patient population for albiglutide. METHODS:
      Two Risk Evaluation and Mitigation Strategy surveys were conducted 18 months and
      3 years after albiglutide was launched. Primary analyses evaluated correct
      response rates for each question. Secondary analyses evaluated the number of
      correct responses and the percentage of respondents scoring at/above the target
      comprehension thresholds (75% at 18 months; 80% at 3 years), which were selected
      based on discussion with the Food and Drug Administration and current standards
      for Risk Evaluation and Mitigation Strategy assessments, for each key risk
      message. RESULTS: The correct response rate for individual questions ranged from
      68.2 to 97.9% (18-month survey) and from 69.4 to 98.1% (3-year survey). For the
      secondary analysis, 79.5, 86.7, and 86.7% of respondents in the 18-month survey
      answered >= 75% of the questions correctly and 70.8, 90.9, and 54.1% of
      respondents in the 3-year survey answered >= 80% of the questions correctly for
      key risk messages related to medullary thyroid carcinoma, pancreatitis, and
      appropriate patient population, respectively. CONCLUSIONS: Survey results
      indicated most, but not all, prescribers are knowledgeable regarding the risks
      and safe use of albiglutide. Additional education to address gaps in knowledge
      could further improve risk mitigation.

PMID- 29218598
TI  - Discrimination threshold for haptic volume perception of fingers and phalanges.
AB  - Humans exhibit a remarkable ability to discriminate variations in object volume
      based on natural haptic perception. The discrimination thresholds for the haptic
      volume perception of the whole hand are well known, but the discrimination
      thresholds for haptic volume perception of fingers and phalanges are still
      unknown. In the present study, two psychophysical experiments were performed to
      investigate haptic volume perception in various fingers and phalanges. The
      configurations of both experiments were completely dependent on haptic volume
      perception from the fingers and phalanges. The participants were asked to blindly
      discriminate the volume variation of regular solid objects in a random order by
      using the distal phalanx, medial phalanx, and proximal phalanx of their index
      finger, middle finger, ring finger, and little finger. The discrimination
      threshold of haptic volume perception gradually decreases from the little finger
      to the index finger as well as from the proximal phalanx to the distal phalanx.
      Overall, both the shape of the target and the part of the finger in contact with
      the target significantly influence the precision of haptic perception of volume.
      This substantial data set provides detailed and compelling perspectives on the
      haptic system, including for discrimination of the spatial size of objects and
      for performing more general perceptual processes.

PMID- 29218596
TI  - Regulation of floral meristem activity through the interaction of AGAMOUS,
      SUPERMAN, and CLAVATA3 in Arabidopsis.
AB  - KEY MESSAGE: Floral meristem size is redundantly controlled by CLAVATA3, AGAMOUS
      , and SUPERMAN in Arabidopsis. The proper regulation of floral meristem activity
      is key to the formation of optimally sized flowers with a fixed number of organs.
      In Arabidopsis thaliana, multiple regulators determine this activity. A small
      secreted peptide, CLAVATA3 (CLV3), functions as an important negative regulator
      of stem cell activity. Two transcription factors, AGAMOUS (AG) and SUPERMAN
      (SUP), act in different pathways to regulate the termination of floral meristem
      activity. Previous research has not addressed the genetic interactions among
      these three genes. Here, we quantified the floral developmental stage-specific
      phenotypic consequences of combining mutations of AG, SUP, and CLV3. Our detailed
      phenotypic and genetic analyses revealed that these three genes act in partially
      redundant pathways to coordinately modulate floral meristem sizes in a spatial
      and temporal manner. Analyses of the ag sup clv3 triple mutant, which developed a
      mass of undifferentiated cells in its flowers, allowed us to identify downstream
      targets of AG with roles in reproductive development and in the termination of
      floral meristem activity. Our study highlights the role of AG in repressing genes
      that are expressed in organ initial cells to control floral meristem activity.

PMID- 29218597
TI  - Role of Tulipa gesneriana TEOSINTE BRANCHED1 (TgTB1) in the control of axillary
      bud outgrowth in bulbs.
AB  - KEY MESSAGE: Tulip vegetative reproduction. Tulips reproduce asexually by the
      outgrowth of their axillary meristems located in the axil of each bulb scale. The
      number of axillary meristems in one bulb is low, and not all of them grow out
      during the yearly growth cycle of the bulb. Since the degree of axillary bud
      outgrowth in tulip determines the success of their vegetative propagation, this
      study aimed at understanding the mechanism controlling the differential axillary
      bud activity. We used a combined physiological and "bottom-up" molecular approach
      to shed light on this process and found that first two inner located buds do not
      seem to experience dormancy during the growth cycle, while mid-located buds enter
      dormancy by the end of the growing season. Dormancy was assessed by weight
      increase and TgTB1 expression levels, a conserved TCP transcription factor and
      well-known master integrator of environmental and endogenous signals influencing
      axillary meristem outgrowth in plants. We showed that TgTB1 expression in tulip
      bulbs can be modulated by sucrose, cytokinin and strigolactone, just as it has
      been reported for other species. However, the limited growth of mid-located buds,
      even when their TgTB1 expression is downregulated, points at other factors,
      probably physical, inhibiting their growth. We conclude that the time of axillary
      bud initiation determines the degree of dormancy and the sink strength of the
      bud. Thus, development, apical dominance, sink strength, hormonal cross-talk,
      expression of TgTB1 and other possibly physical but unidentified players, all
      converge to determine the growth capacity of tulip axillary buds.

PMID- 29218599
TI  - Rich and Well Educated: Are These Requirements Necessary to Claim Healthcare Tax
      Credits in Italy?
AB  - BACKGROUND: The paper investigates the use of healthcare tax credits (HTCs) in
      Italy through the analysis of a panel data, which provides information on
      individual income tax from 2008 to 2014. There is evidence of disparities in the
      per-capita HTCs between Northern and Southern regions, which need to be analyzed
      and addressed. OBJECTIVE: The aim of the paper is to investigate the
      socioeconomic determinants in the use of Healthcare Tax Credits in Italy.
      METHODS: A fixed effects Ordinary Least Square model is run to analyze the impact
      of selected socioeconomic variables on regional per capita HTCs, with a
      particular focus on the role of education. RESULTS: The results corroborate
      literature findings on the regressive effects of HTCs; they also provide
      highlights on the role of education in explaining the distribution of HTCs among
      Italian regions. CONCLUSION: Public money is reimbursed to regions where people
      are, on average, richer and better educated. More equitable objectives could be
      reached by allocating the same resources in the provision of services covered by
      the NHS.

PMID- 29218600
TI  - The SH3-binding domain of Cx43 participates in loop/tail interactions critical
      for Cx43-hemichannel activity.
AB  - Connexin 43 (Cx43) hemichannels establish local signaling networks via the
      release of ATP and other molecules, but their excessive opening may result in
      cell death. Hence, the activity of Cx43-hemichannels ought to be critically
      controlled. This involves interactions between the C-terminal tail (CT) and the
      cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work
      revealed an important role for the last nine amino acids of the Cx43 CT by
      targeting the L2 domain, as these nine amino acids were sufficient to restore the
      activity of CT-truncated Cx43-hemichannels. However, we discovered that deletion
      of the last 19 amino acids of the CT only partially lowered the binding to the L2
      domain, indicating that a second L2-binding region is present in the CT. We here
      provide evidence that the SH3-binding domain is another CT region that targets
      the L2 domain. At the functional level, the SH3-binding domain was able to
      restore the activity of CT-truncated Cx43-hemichannels and alleviate the
      inhibition of full-length Cx43-hemichannels by high intracellular Ca2+
      concentration ([Ca2+]i) as demonstrated by various approaches including patch
      clamp studies of unitary Cx43-hemichannel activity. Finally, we show that in full
      length Cx43-hemichannels, deletion of either the SH3-binding domain or the CT9
      region suppresses the hemichannel activity, while deletion of both domains
      completely annihilates the hemichannel activity. These results demonstrate that
      the Cx43 SH3-binding domain, in addition to the CT9 region, critically controls
      hemichannel activity at high [Ca2+]i, which may be involved in pathological
      hemichannel opening.

PMID- 29218602
TI  - Correlates of Serosorting and Knowledge of Sexual Partner's HIV Status Among Men
      Who have Sex with Men in Ukraine.
AB  - Ukraine has among the highest rates of newly diagnosed HIV infections in the WHO
      European region. Men who have sex with men (MSM) is the least studied group in
      the context of the HIV epidemics in Ukraine. The present paper aims to estimate
      the prevalence and correlates of knowledge of sexual partner's HIV status and
      potentially discordant anal intercourse (failure to serosort) among MSM. Data of
      the cross-sectional study among 8100 MSM in Ukraine in 2013 were used for this
      analysis. Less than half of the participants (42.5%) reported that they knew the
      HIV serostatus of their most recent male sexual partner, and about 13% of
      participants reported failure to serosort during their most recent anal sexual
      intercourse with a male partner. Targeted interventions can be implemented to
      increase knowledge about sexual partner's HIV status, both among HIV-negative and
      HIV-positive MSM, to reduce the risk of HIV acquisition and transmission.

PMID- 29218603
TI  - Characteristics of unintentional drowning deaths in children with autism spectrum
      disorder.
AB  - BACKGROUND: The reported prevalence of autism spectrum disorder (ASD) has
      increased markedly in the past two decades. Recent research indicates that
      children with ASD are at a substantially increased risk of injury mortality,
      particularly from unintentional drowning. The purpose of this study was to
      explore the circumstances of fatal unintentional drowning incidents involving
      children with ASD under 15 years of age. FINDINGS: During January 2000 through
      May 2017, US newspapers reported a total of 23 fatal drowning incidents involving
      18 boys and 5 girls with ASD. Age of victims ranged from 3 to 14 years (mean =
      7.7 +/- 2.9 years). These drowning incidents most commonly occurred in ponds
      (52.2%), followed by rivers (13.0%), and lakes (13.0%). For 11 incidents with
      location data available, the distance between victim residence and the water body
      where drowning occurred averaged 290.7 m (+/- 231.5 m). About three-quarters
      (73.3%) of the drowning incidents occurred in the afternoon hours from 12:00 to
      18:59. Wandering was the most commonly reported activity that led to drowning,
      accounting for 73.9% of the incidents. CONCLUSIONS: Fatal drowning in children
      with ASD typically occur in water bodies near the victims' homes in the afternoon
      hours precipitated by wandering. Multifaceted intervention programs are urgently
      needed to reduce the excess risk of drowning in children with ASD.

PMID- 29218604
TI  - Author Correction to: Extreme Learning Machine Framework for Risk Stratification
      of Fatty Liver Disease Using Ultrasound Tissue Characterization.
AB  - The original version of this article unfortunately contained a mistake. The
      family name of Rui Tato Marinho was incorrectly spelled as Marinhoe.

PMID- 29218601
TI  - Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases.
AB  - Hematopoiesis is hierarchically orchestrated by a very small population of
      hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are
      tightly regulated to maintain homeostatic blood production. HSCs are
      predominantly quiescent, but they enter the cell cycle in response to
      inflammatory signals evoked by severe systemic infection or injury. Thus,
      hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen
      recognition receptors and proinflammatory cytokines to induce emergency
      myelopoiesis during infection. This emergency myelopoiesis counterbalances the
      loss of cells and generates lineage-restricted hematopoietic progenitors,
      eventually replenishing mature myeloid cells to control the infection. Controlled
      generation of such signals effectively augments host defense, but dysregulated
      stimulation by these signals is harmful to HSPCs. Such hematopoietic failure
      often results in blood disorders including chronic inflammatory diseases and
      hematological malignancies. Recently, we found that interleukin (IL)-27, one of
      the IL-6/IL-12 family cytokines, has a unique ability to directly act on HSCs and
      promote their expansion and differentiation into myeloid progenitors. This
      process resulted in enhanced production of neutrophils by emergency myelopoiesis
      during the blood-stage mouse malaria infection. In this review, we summarize
      recent advances in the regulation of myelopoiesis by proinflammatory cytokines
      including type I and II interferons, IL-6, IL-27, granulocyte colony-stimulating
      factor, macrophage colony-stimulating factor, and IL-1 in infectious diseases.

PMID- 29218605
TI  - Oxymatrine Sensitizes the HaCaT Cells to the IFN-gamma Pathway and Downregulates
      MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt.
AB  - Decreased interferon (IFN)-gamma levels and increased levels of macrophage
      derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to
      be involved in allergic skin diseases, such as eczema and atopic dermatitis.
      Activation of the IFN-gamma and its downstream interleukin-12 (IL-12) pathway can
      correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine
      signaling inhibitor that blocks downstream pathways of IFN-gamma by blocking the
      mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling
      pathways. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the herbal
      medicine Radix Sophorae flavescentis, is used to treat allergic skin diseases in
      China. The non-cytotoxic concentrations of OMT in HaCaT cells were determined
      through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assays. Tumor necrosis factor (TNF)-alpha and IFN-gamma were used to stimulate
      HaCaT cells, and OMT was added to this system with tacrolimus (FK506) as a
      positive control. The mRNAs of cytokines, MDC, ICAM-1, IL-12p35, IL-12p40, and
      IFN-gamma receptor (IFN-gammaR)alpha were detected by RT-PCR. Western blot
      analyses were performed to assess activation of the MAPK (p38, Jun N-terminal
      kinase, and extracellular signal-regulated kinase) and Akt signaling pathways.
      OMT increased the mRNA levels of the IL-12 and IFN-gammaRalpha, reduced the mRNA
      levels of ICAM-1, MDC, and SOCS1. But FK506 increased the mRNA levels of IL12 and
      inhibited the expression of ICAM-1 mRNAs and had no effects on the IFN
      gammaRalpha, MDC, and SOCS1 mRNA in HaCaT cells stimulated with TNF-alpha and IFN
      gamma. Thus, the mechanisms through which OMT and FK506 ameliorate allergic skin
      diseases differ.

PMID- 29218606
TI  - PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional
      Activation at the Promoter Level.
AB  - L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are adhesion molecules
      which induce similar physiological events. Our previous paper showed that
      phosphatidylinositol 3-kinase (PI3K) played a crucial role in L-selectin- and
      PSGL-1-mediated F-actin redistribution and assembly during neutrophil rolling on
      E-selectin. However, it is not clear whether L-selectin and PSGL-1 induce other
      similar physiology events by PI3K. Here, we investigated the possibility of PI3K
      linking the signaling pathways of L-selectin and PSGL-1 to IL-18 transcription.
      We first demonstrated that L-selectin and PSGL-1 stimulation upregulated IL-18
      transcription level in Jurkat cells. Then we found that PI3K inhibitor LY294002
      reduced L-selectin- and PSGL-1-induced mRNA upregulation of IL-18 in Jurkat
      cells. Transfection of phosphatase and tensin homolog expressing plasmid
      inhibited the transcription level of IL-18. Therefore, PI3K is a signal linker
      between L-selectin and PSGL-1 in IL-18 transcriptional activation at the promoter
      level. To our knowledge, this is the first time to directly link PI3K to L
      selectin- and PSGL-1-mediated IL-18 transcription, providing a foundation for
      intervention of PI3K-related inflammation.

PMID- 29218607
TI  - [Chemokines in ophthalmology].
AB  - Chemokines are chemotactically active cytokines, which coordinate the
      distribution of immune cells within the body and also regulate the migration of
      leukocytes in malignant and inflammatory processes. Chemokines are a
      heterogeneous group of short-chain proteins that are divided into different
      subgroups on the basis of their structure. In addition to the chemokines
      (ligands) various chemokine receptors also exist. The chemokine system is given
      its complexity by the high redundancy of ligand-receptor interactions: one single
      ligand can bind to different receptors and a single receptor can interact with
      different ligands. In terms of receptors, distinct immune cell types have
      characteristic receptor expression patterns, which can be used for the
      immunological characterization of leukocytes. Important basic research is
      currently leading to a better understanding of the chemokine system. The
      essential importance of the chemokine system in various diseases of the anterior
      and posterior eye segments is becoming increasingly apparent. The following
      synopsis explains the individual clinical aspects as well as the underlying
      scientific work in the context of "chemokines in ophthalmology".

PMID- 29218609
TI  - Abstracts of EMC2017.

PMID- 29218608
TI  - [Correction: Trends in retinal detachment surgery : What has changed compared to
      2001?]

PMID- 29218610
TI  - Feasibility of whole-body diffusion-weighted MRI for detection of primary tumour,
      nodal and distant metastases in women with cancer during pregnancy: a pilot
      study.
AB  - OBJECTIVES: To evaluate the feasibility of whole-body diffusion-weighted MRI (WB
      DWI/MRI) for detecting primary tumour, nodal and distant metastases in pregnant
      women with cancer. METHODS: Twenty pregnant patients underwent WB-DWI/MRI in
      additional to conventional imaging. Reproducibility of WB-DWI/MRI between two
      readers was evaluated using Cohen's kappa statistics and accuracy was compared to
      conventional imaging for assessing primary tumour site, nodal and visceral
      metastases. RESULTS: Both WB-DWI/MRI readers showed good-very good agreement for
      lesion detection (primary lesions: kappa=1; lymph nodes: kappa=0.89; distant
      metastases: kappa=0.61). Eight (40 %) patients were upstaged after WB-DWI/MRI.
      For nodal metastases, WB-DWI/MRI showed 100 % (95 % CI: 83.2-100) sensitivity for
      both readers with specificity of 99.4 % (96.9-100) and 100 % (80.5-100) for
      readers 1 and 2, respectively. For distant metastases, WB-DWI/MRI showed 66.7 %
      (9.4-99.2) and 100 % (29.2-100) sensitivity and specificity of 94.1 % (71.3-99.9)
      and 100 % (80.5-100) for readers 1 and 2, respectively. Conventional imaging
      showed sensitivity of 50 % (27.2-72.8) and 33.3 % (0.8-90.6); specificity of 100
      % (98-100) and 100 % (80.5-100), for nodal and distant metastases respectively.
      CONCLUSIONS: WB-DWI/MRI is feasible for single-step non-invasive staging of
      cancer during pregnancy with additional value for conventional imaging
      procedures. KEY POINTS: * In our study, WB-DWI/MRI was more accurate than
      conventional imaging during pregnancy. * WB-DWI/MRI improves diagnostic
      assessment of patients with cancer during pregnancy. * Accurate imaging and
      oncologic staging improves treatment and outcome.

PMID- 29218611
TI  - Portal hypertension is associated with poor outcome of transarterial
      chemoembolization in patients with hepatocellular carcinoma.
AB  - OBJECTIVES: To determine whether clinically relevant portal hypertension (CRPH)
      influences outcome and whether it may serve as a prognostic marker in patients
      treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma
      (HCC). METHODS: One hundred and forty-seven patients underwent conventional TACE
      as a first-line treatment for a single HCC. CRPH was graded as 0, 1, or 2. The
      influence of CRPH, together with other factors, on local tumour progression (LTP)
      and overall survival (OS) were analysed using Cox proportional hazards
      regression. RESULTS: A higher CRPH grade (grade 1, p = 0.005, hazard ratio [HR] =
      3.282; grade 2, p < 0.001, HR = 7.144) and less selective catheterization (p =
      0.009, HR = 1.951) were significantly associated with early LTP. Regarding OS,
      older age, (p < 0.001, HR = 1.050), CRPH grade 2 (p = 0.024, HR = 2.058), and a
      larger tumour (p < 0.001, HR = 1.454) were significantly associated with early
      death. CONCLUSIONS: Portal hypertension was significantly associated with poor
      outcome after TACE, and non-invasive CRPH grading may be a useful prognostic
      marker of TACE. KEY POINTS: * Portal hypertension was significantly associated
      with poor outcome after TACE. * Grading portal hypertension non-invasively can
      help predict TACE outcome in HCC patients. * CRPH grading can aid in selecting
      optimal candidates for TACE.

PMID- 29218612
TI  - Transoesophageal echocardiography prior to catheter ablation could be avoided in
      atrial fibrillation patients with a low risk of stroke and without filling
      defects in the late-phase MDCT scan: A retrospective analysis of 783 patients.
AB  - OBJECTIVES: To test whether multidetector computed tomography (MDCT) could
      completely replace transoesophageal echocardiography (TEE) to detect left atrial
      appendage (LAA) thrombi in atrial fibrillation (AF) patients using a large sample
      size. METHODS: 783 patients with AF who underwent MDCT and TEE before catheter
      ablation were retrospectively included. Demographic data were obtained. Two
      radiologists blinded to clinical data made the imaging diagnosis. RESULTS: Most
      of the patients (96.2 %) had a CHA2DS2-VASc score (congestive heart failure,
      hypertension, age >= 75 years old (doubled), diabetes, stroke/transient ischaemic
      attack/thromboembolism (doubled), vascular disease, age 65-74 years, female sex)
      <= 3. Eight thrombi were identified by TEE, all of which were detected by MDCT;
      no thrombus was observed with TEE without the observation of filling defects by
      late-phase MDCT scanning in any of the patients. Using TEE as reference standard,
      the sensitivity, specificity, positive predictive value and negative predictive
      value of MDCT for thrombus detection were 100 %, 95.74 % (95 % CI 94.33 %-97.15
      %), 19.51 % (95 % CI 16.73 %-22.29 %) and 100 %, respectively. CONCLUSIONS: For
      AF patients with low risk of stroke, when MDCT images showed no filling defect in
      the late phase, TEE prior to catheter ablation can be avoided. KEY POINTS: * MDCT
      can help detect the presence of LAA thrombus. * TEE can be avoided when late
      phase MDCT shows no filling defect. * TEE is required in patients whose MDCT
      images indicate thrombus.

PMID- 29218613
TI  - Can We Perform CT of the Appendix with Less Than 1 mSv? A De-escalating Dose
      simulation Study.
AB  - OBJECTIVES: To systematically explore the lowest reasonably achievable radiation
      dose for appendiceal CT using an iterative reconstruction (IR) in young adults.
      METHODS: We prospectively included 30 patients who underwent 2.0-mSv CT for
      suspected appendicitis. From the helical projection data, 1.5-, 1.0- and 0.5-mSv
      CTs were generated using a low-dose simulation tool and the knowledge-based IR.
      We performed step-wise non-inferiority tests sequentially comparing 2.0-mSv CT
      with each of 1.5-, 1.0- and 0.5-mSv CT, with a predetermined non-inferiority
      margin of 0.06. The primary end point was the pooled area under the receiver
      operating-characteristic curve (AUC) for three abdominal and three non-abdominal
      radiologists. RESULTS: For the abdominal radiologists, the non-inferiorities of
      1.5-, 1.0- and 0.5-mSv CT to 2.0-mSv CT were sequentially accepted [pooled AUC
      difference: 2.0 vs. 0.5 mSv, 0.017 (95% CI: -0.016, 0.050)]. For the non
      abdominal radiologists, the non-inferiorities of 1.5- and 1.0-mSv CT were
      accepted; however, the non-inferiority of 0.5-mSv CT could not be proved [pooled
      AUC difference: 2.0 vs. 1.0 mSv, -0.017 (-0.070, 0.035) and 2.0 vs. 0.5 mSv,
      0.045 (-0.071, 0.161)]. CONCLUSION: The 1.0-mSv appendiceal CT was non-inferior
      to 2.0-mSv CT in terms of diagnostic performance for both abdominal and non
      abdominal radiologists; 0.5-mSv appendiceal CT was non-inferior only for
      abdominal radiologists. KEY POINTS: * For both abdominal and non-abdominal
      radiologists, 1.0-mSv appendiceal CT could be feasible. * The 0.5-mSv CT was non
      inferior to 2.0-mSv CT only for expert abdominal radiologists. * Reader
      experience is an important factor affecting diagnostic impairment by low-dose CT.

PMID- 29218614
TI  - 18F-fluorodeoxyglucose specimen-positron emission mammography delineates tumour
      extension in breast-conserving surgery: Preliminary results.
AB  - OBJECTIVES: We aimed to determine whether high-resolution specimen-positron
      emission mammography (PEM) using fluorodeoxyglucose (18F-FDG) can reveal
      extension of breast cancer in breast-conserving surgery (BCS), and assess the
      safety of radiation exposure to medical staff. METHODS: Sixteen patients
      underwent positron emission tomography, and then BCS with intraoperative frozen
      section analysis on the same day. Resected specimens with remaining 18F-FDG
      accumulation were scanned by high-resolution PEM. At least 1 day after surgery,
      tumour extension was evaluated by three independent experienced readers and by
      binarized images from the specimen-PEM data. Intraoperative exposure of medical
      staff to 18F-FDG was measured. RESULTS: Specimen-PEM evaluations of binarized
      images and the three investigators detected all (100 %, 12/12) invasive lesions
      and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive
      value of the accumulated lesions was 74.4 % (29/39) for the binarized images and
      82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen
      sections detected 100 % (2/2) of the margin-positive cases, also detected by both
      specimen-PEM evaluation methods with no false-positive margin cases. The mean
      exposure of the medical staff to 18F was 18 MUSv. CONCLUSIONS: Specimen-PEM
      detected invasive and in situ lesions with high accuracy and allowable radiation
      exposure. KEY POINTS: * Specimen-PEM detected invasive and in situ lesions with
      high accuracy. * Specimen-PEM predicted complete resection with the same accuracy
      as frozen section analysis. * Breast-conserving surgery after fluorodeoxyglucose
      injection was performed with low medical staff exposure.

PMID- 29218615
TI  - Advanced CT for diagnosis of seizure-related stroke mimics.
AB  - BACKGROUND AND PURPOSE: It is assumed that up to 30 % of clinically diagnosed
      acute ischaemic strokes (AIS) are actually stroke mimics (SM). Our aim was to
      evaluate the usefulness of advanced CT including CT angiography (CTA) and CT
      perfusion (CTP) findings when distinguishing AIS from seizure-related SM.
      METHODS: Over a 22-month period data were gathered of patients who presented to
      our stroke centre with AIS-like symptoms and were examined immediately with an
      advanced CT, analysed and evaluated by two experienced neuroradiologists who
      preferred SM rather than AIS. All these patients additionally received
      electroencephalography and follow-up imaging. CTA was the important feature to
      exclude vessel occlusion or haemodynamic relevant stenosis. Perfusion patterns
      were retrospectively analysed qualitatively. RESULTS: The most common perfusion
      abnormality was cortical hyperperfusion (22/37 [59.5 %] patients) followed by a
      hypoperfusion pattern with a cortical-subcortical involvement (15/37 [40.5 %]
      patients) without evidence of vessel occlusion or stenosis. Seizure-related hyper
      and hypoperfusion patterns typically crossed the normal anatomical vascular
      territories boundaries. CONCLUSION: Beyond its use in core and penumbra
      estimation, advanced CT provides important information to emergency physicians in
      the difficult clinical diagnosis when differentiating between AIS and seizure
      related symptoms with an important impact on therapeutic decision-making. KEY
      POINTS: * Advanced CT helps to differentiate between ischaemic strokes and stroke
      mimics. * Seizure-related perfusion patterns are distinct from ischaemia
      hypoperfusion. * Advanced CT could improve rapid adequate treatment for AIS and
      seizure events.

PMID- 29218616
TI  - Noninvasive assessment of hepatic sinusoidal obstructive syndrome using acoustic
      radiation force impulse elastography imaging: A proof-of-concept study in rat
      models.
AB  - OBJECTIVES: To determine the feasibility of acoustic radiation force impulse
      (ARFI) elastography in the evaluation of hepatic sinusoidal obstruction syndrome
      (SOS) in rat models. METHODS: Rat SOS models of various severities were created
      by monocrotaline gavage (n = 40) or by intraperitoneal injection of 5
      fluorouracil, leucovorin and oxaliplatin (FOLFOX) (n = 16). Liver shear-wave
      velocity (SWV) was measured using ARFI elastography. Liver samples were analysed
      for the SOS score, steatosis, lobular inflammation and fibrosis. RESULTS: The
      liver SWV was significantly elevated in the SOS models (1.29-2.24 m/s) compared
      with that of the matched control rats (1.01-1.09; p<=.09; veFor seven FOLFOX
      treated rats which were longitudinally followed-up, the liver SWV significantly
      increased at 7 weeks (1.32+/-0.13 m/s) compared with the baseline (1.08+/-0.1
      m/s, p=.015) and then significantly declined after a 2-week, treatment-free
      period (1.15+/-0.13 m/s; p=.048). Multivariate analysis revealed that the SOS
      score (p<.001) and lobular inflammation (p=.044) were independently correlated
      with the liver SWV. CONCLUSION: Liver SWV is elevated in SOS in proportion to the
      degree of sinusoidal injury and lobular inflammation in rat SOS models. ARFI
      elastography has potential as an examination for diagnosis, severity assessment
      and follow-up of SOS. KEY POINTS: * Liver SWV using ARFI elastography was
      significantly elevated in SOS rat. * Sinusoidal injury and lobular inflammation
      grades had correlation with liver SWV. * ARFI elastography has potential for
      diagnosis, severity assessment, and follow-up of SOS.

PMID- 29218617
TI  - Evaluation of an adaptive detector collimation for prospectively ECG-triggered
      coronary CT angiography with third-generation dual-source CT.
AB  - OBJECTIVES: To investigate the impact of an adaptive detector collimation on the
      dose parameters and accurateness of scan length adaption at prospectively ECG
      triggered sequential cardiac CT with a wide-detector third-generation dual-source
      CT. METHODS: Ideal scan lengths for human hearts were retrospectively derived
      from 103 triple-rule-out examinations. These measures were entered into the new
      scanner operated in prospectively ECG-triggered sequential cardiac scan mode with
      three different detector settings: (1) adaptive collimation, (2) fixed 64 * 0.6
      mm collimation, and (3) fixed 96 * 0.6-mm collimation. Differences in effective
      scan length and deviation from the ideal scan length and dose parameters
      (CTDIvol, DLP) were documented. RESULTS: The ideal cardiac scan length could be
      matched by the adaptive collimation in every case while the mean scanned length
      was longer by 15.4% with the 64 * 0.6 mm and by 27.2% with the fixed 96 * 0.6-mm
      collimation. While the DLP was almost identical between the adaptive and the 64 *
      0.6-mm collimation (83 vs. 89 mGycm at 120 kV), it was 62.7% higher with the 96 *
      0.6-mm collimation (135 mGycm), p < 0.001. CONCLUSION: The adaptive detector
      collimation for prospectively ECG-triggered sequential acquisition allows for
      adjusting the scan length as accurate as this can only be achieved with a spiral
      acquisition. This technique allows keeping patient exposure low where patient
      dose would significantly increase with the traditional step-and-shoot mode. KEY
      POINTS: * Adaptive detector collimation allows keeping patient exposure low in
      cardiac CT. * With novel detectors the desired scan length can be accurately
      matched. * Differences in detector settings may cause 62.7% of excessive dose.

PMID- 29218618
TI  - Metal artifact reduction MRI of total ankle arthroplasty implants.
AB  - OBJECTIVES: To assess high-bandwidth and compressed sensing-(CS)-SEMAC turbo spin
      echo (TSE) techniques for metal artifact reduction MRI of total ankle
      arthroplasty (TAA) implants. METHODS: Following institutional approval and
      consent, 40 subjects with TAA implants underwent 1.5-T MRI prospectively.
      Evaluations included bone-implant interfaces, anatomical structures, abnormal
      findings and differential diagnoses before and after MRI. AUCs of P-P plots were
      used to determine superiority. Statistical differences were evaluated with
      McNemar and chi-square tests. P-values <= 0.05 were considered significant.
      RESULTS: CS-SEMAC TSE was superior to high-bandwidth TSE in showing the bone
      implant interfaces (AUC=0.917), periprosthetic bone, tendons and joint capsule
      (AUC=0.337-0.766), bone marrow oedema (43 % difference, p=0.041), interface
      osteolysis (63 %, p=0.015), tendinopathy (62 %, p=0.062), periprosthetic
      fractures (60 %, p=0.250), synovitis (43 %, p=0.250), as well as reader
      confidence for bone marrow oedema (p=<0.001), fracture (p=0.001), interface
      osteolysis (p=0.003), synovitis (p=0.027) and tendinopathy (p=0.034). The number
      of differential diagnoses in symptomatic subjects after the MRI with CS-SEMAC
      decreased from 3 (1-4) to 1 (1-2) (p<0.001). CONCLUSIONS: MRI of TAA implants
      with CS-SEMAC improves the diagnosis of interface osteolysis, periprosthetic bone
      marrow oedema, fractures and tendinopathy when compared to high-BW TSE, and has a
      positive effect on patient management. KEY POINTS: * High-bandwidth TSE and
      compressed sensing SEMAC improve MRI of ankle arthroplasty implants. * Compressed
      sensing SEMAC improves bone-implant interfaces, periprosthetic bone, tendons and
      joint capsule visibility. * Compressed sensing SEMAC improves the diagnosis of
      osteolysis, tendinopathy, fractures and synovitis. * MRI decreases the number of
      clinical differential diagnoses of painful ankle arthroplasty implants.

PMID- 29218619
TI  - Cervical ultrasonography has no additional value over negative 18F-FDG PET/CT
      scans for diagnosing cervical lymph node metastases in patients with oesophageal
      cancer.
AB  - OBJECTIVES: To investigate the additional value of cervical ultrasonography over
      18F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with
      newly diagnosed oesophageal cancer. METHODS: Between January 2013 and January
      2016, 163 patients with newly diagnosed oesophageal cancer underwent both
      cervical ultrasonography and 18F-FDG PET/CT at a tertiary referral centre in the
      Netherlands. Retrospective clinical data analysis was performed to assess the
      diagnostic value of cervical ultrasonography and 18F-FDG PET/CT for the detection
      of cervical lymph node metastases. Fine needle aspiration or clinical follow-up
      was used as reference standard. RESULTS: The overall incidence of patients with
      cervical lymph node metastases was 14%. The sensitivity of 18F-FDG PET/CT to
      detect cervical lymph node metastases was 82% (95% CI 59-94%) and specificity was
      91% (95% CI 85-95%). The sensitivity and specificity of cervical ultrasonography
      were 73% (95% CI 50-88%) and 84% (95% CI 77-90%), respectively. In patients with
      a negative 18F-FDG PET/CT, 12 of 133 (9%) patients had suspicious nodes on
      cervical ultrasonography. In all these 12 patients the nodes were confirmed
      benign. CONCLUSIONS: Cervical ultrasonography has no additional diagnostic value
      to a negative integrated 18F-FDG PET/CT for the detection of cervical lymph node
      metastases in patients with newly diagnosed oesophageal cancer. KEY POINTS: *
      Cervical ultrasonography has no value over PET/CT in evaluating cervical node
      metastases. * PET/CT provides greater diagnostic confidence compared to cervical
      ultrasonography. * Cervical ultrasonography during standard diagnostic work-up
      may be considered unnecessary. * Cervical lesions on PET/CT require
      cytopathological confirmation by FNA.

PMID- 29218620
TI  - The impact of injector-based contrast agent administration in time-resolved MRA.
AB  - OBJECTIVES: Time-resolved contrast-enhanced MR angiography (4D-MRA), which allows
      the simultaneous visualization of the vasculature and blood-flow dynamics, is
      widely used in clinical routine. In this study, the impact of two different
      contrast agent injection methods on 4D-MRA was examined in a controlled,
      standardized setting in an animal model. METHODS: Six anesthetized Goettingen
      minipigs underwent two identical 4D-MRA examinations at 1.5 T in a single
      session. The contrast agent (0.1 mmol/kg body weight gadobutrol, followed by 20
      ml saline) was injected using either manual injection or an automated injection
      system. A quantitative comparison of vascular signal enhancement and quantitative
      renal perfusion analyses were performed. RESULTS: Analysis of signal enhancement
      revealed higher peak enhancements and shorter time to peak intervals for the
      automated injection. Significantly different bolus shapes were found: automated
      injection resulted in a compact first-pass bolus shape clearly separated from the
      recirculation while manual injection resulted in a disrupted first-pass bolus
      with two peaks. In the quantitative perfusion analyses, statistically significant
      differences in plasma flow values were found between the injection methods.
      CONCLUSIONS: The results of both qualitative and quantitative 4D-MRA depend on
      the contrast agent injection method, with automated injection providing more
      defined bolus shapes and more standardized examination protocols. KEY POINTS: *
      Automated and manual contrast agent injection result in different bolus shapes in
      4D-MRA. * Manual injection results in an undefined and interrupted bolus with two
      peaks. * Automated injection provides more defined bolus shapes. * Automated
      injection can lead to more standardized examination protocols.

PMID- 29218621
TI  - The efficacy of real-time colour Doppler flow imaging on endoscopic
      ultrasonography for differential diagnosis between neoplastic and non-neoplastic
      gallbladder polyps.
AB  - OBJECTIVES: We evaluated the usefulness of real-time colour Doppler flow (CDF)
      endoscopic ultrasonography (EUS) for differentiating neoplastic gallbladder (GB)
      polyps from non-neoplastic polyps. METHODS: Between August 2014 and December
      2016, a total of 233 patients with GB polyps who underwent real-time CDF-EUS were
      consecutively enrolled in this prospective study. CDF imaging was subjectively
      categorized for each patient as: strong CDF pattern, weak CDF pattern and no CDF
      pattern. RESULTS: Of the 233 patients, 115 underwent surgical resection. Of
      these, there were 90 cases of non-neoplastic GB polyps and 23 cases of neoplastic
      GB polyps. In a multivariate analysis, a strong CDF pattern was the most
      significant predictive factor for neoplastic polyps; sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy were 52.2 %,
      79.4 %, 38.7 %, 86.9 % and 73.9 %, respectively. Solitary polyp and polyp size
      were associated with an increased risk of neoplasm. CONCLUSIONS: The presence of
      a strong CDF pattern as well as solitary and larger polyps on EUS may be
      predictive of neoplastic GB polyps. As real-time CDF-EUS poses no danger to the
      patient and requires no additional equipment, it is likely to become a
      supplemental tool for the differential diagnosis of GB polyps. KEY POINTS: *
      Differential diagnosis between neoplastic polyps and non-neoplastic polyps of GB
      is limited. * The use of real-time CDF-EUS was convenient, with high agreement
      between operators. * The real-time CDF-EUS is helpful in differential diagnosis
      of GB polyps.

PMID- 29218622
TI  - Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions.
AB  - Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled
      proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are
      involved in the regulation of the cell cycle, are frequently overexpressed or
      mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated
      as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to
      be relatively safe and effective, and these are now standard of care treatment
      for advanced hormone receptor positive breast cancer. Some CDK4/6i drugs are also
      able to cross the blood brain barrier and may, therefore, offer effective therapy
      for primary and metastatic central nervous system malignancies. Ongoing research
      is also evaluating CDK4/6i for additional breast cancer subtypes and non-breast
      malignancies with promising early phase clinical trial results. Finally, pre
      clinical research has identified potential biomarkers for CDK4/6i efficacy and is
      exploring potential resistance mechanisms to this treatment. Further clinical
      translational research is needed to advance patient selection and combinatorial
      treatment strategies with CDK4/6i in breast cancer and other malignancies.

PMID- 29218623
TI  - Early Metabolic Change after Induction Chemotherapy Predicts Histologic Response
      and Prognosis in Patients with Esophageal Cancer: Secondary Analysis of a
      Randomized Trial.
AB  - BACKGROUND: Early metabolic response after preoperative induction chemotherapy
      (IC) appears to predict histologic response and prognosis in esophageal cancer
      (EC), but the usefulness of this approach needs further development. OBJECTIVE:
      We evaluated metabolic response after one cycle of IC using positron emission
      tomography (PET) to correlate PET response and outcomes. PATIENTS AND METHODS: We
      retrospectively analyzed PET data from a randomized phase 2 trial (NCT00525915)
      of chemoradiation and surgery with or without IC for the treatment of EC. PET was
      performed at baseline, after one cycle of IC, and 5-7 weeks after chemoradiation.
      The relationship between PET response (>=35% reduction in standardized uptake
      value [SUV]) after IC and treatment response was analyzed. RESULTS: In 63
      patients who received IC, the mean initial SUVmax prior to treatment was 11.9 +/-
      8.04 and mean SUVmax after one cycle of IC was 6.47 +/- 4.45. The mean SUV
      reduction after IC was 39.3%. Eleven of 37 PET responders achieved a pathologic
      complete response (pCR), but only two of 22 PET non-responders did (univariate
      logistic regression; odds ratio: 4.25, 95% confidence interval: 0.83-21.77; p =
      0.08). PET responders to IC had significantly longer overall survival (OS) than
      PET nonresponders (log-rank p = 0.009). PET response after chemoradiation was not
      correlated with OS (log-rank p = 0.15). CONCLUSION: Early PET response after IC
      is prognostic, but subsequent PET changes (for example, after chemoradiation) are
      not prognostic. Early PET response might have the potential of predicting pCR.

PMID- 29218624
TI  - Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program.
AB  - Metastatic cancers impose significant burdens on patients, affecting quality of
      life, morbidity, and mortality. Even during remission, microscopic metastases can
      lurk, but few therapies directly target tumor cell metastasis. Agents that
      interfere with this process would represent a new paradigm in cancer management,
      changing the 'waiting game' into a time of active prevention. These therapies
      could take multiple forms based on the pathways involved in the metastatic
      process. For example, a phenome-wide association study showed that a single
      nucleotide polymorphism in the gene TBXA2R is associated with increased
      metastasis in multiple primary cancers (P = 0.003), suggesting clinical
      applicability of TBXA2R antagonists. Emerging data related to the role of
      platelets in metastasis are concordant with our sense that these pathways present
      significant opportunities for therapeutic development. However, before real
      progress can be made toward clinical targeting of the metastatic process,
      foundational work is needed to define informative measures of critical elements
      such as circulating tumor cells and tumor DNA, and circulatory vs. lymphatic
      spread. These challenges require an expansion of team science and composition to
      obtain competitive funding. At our academic medical center, we have implemented a
      Cancer Metastasis Inhibition (CMI) program investigating this approach across
      multiple cancers.

PMID- 29218625
TI  - Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and
      Calcium Channel Blocker.
AB  - BACKGROUND: In patients already receiving combination of angiotensin-converting
      enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel
      blocker (CCB), whether the choice of additional diuretic or beta-blocker affects
      the cardiovascular and cerebrovascular outcomes remains unclear. METHODS: A total
      of 13,551 patients who were concurrently receiving three anti-hypertensive agents
      of different classes through outpatient clinics during 2004-2006 were identified
      from the National Health Insurance Research Database of Taiwan. Patients were
      further classified into two treatment groups according to the medication
      possession ratio of drug combinations; the A + B + C group as those who received
      concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as
      patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of
      stroke, acute myocardial infarction (AMI), mortality, and major adverse
      cardiovascular events (MACE) between the two treatment groups was investigated.
      RESULTS: After propensity score matching, there were 5120 patients in each group.
      There were no differences in the incidence of cardiovascular events between the
      two groups. In patients with prior history of cerebrovascular accident (CVA), the
      A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56;
      95% CI 1.051-2.307; p < 0.05) as compared with the A + B + C group. CONCLUSION:
      Adding a diuretic may be better than adding a beta-blocker for treating
      hypertensive patients with prior CVA history who have already received ACEIs/ARBs
      and CCBs.

PMID- 29218626
TI  - Treatment-related changes in glioblastoma: a review on the controversies in
      response assessment criteria and the concepts of true progression,
      pseudoprogression, pseudoresponse and radionecrosis.
AB  - The assessment of response to therapy in glioblastoma remains a challenge,
      because the surrogate measures of survival are subject to radiographic
      misinterpretation. A solid and reliable definition of progression is needed for
      both clinical decision-making and for evaluating response within the clinical
      trials. Historically, assessment criteria have used radiologic and clinical
      features aimed to correctly classify patients into progressive or non-progressive
      disease. The widely used RANO criteria are a valuable tool in disease evaluation,
      both in the clinical setting and in the clinical trials. However, assessment
      criteria have certain limitations that emerging image techniques have tried to
      overcome. Differentiating true progression from treatment-related changes (like
      pseudoprogression or pseudoresponse) is crucial in order not to prematurely
      discontinue adjuvant chemotherapy or redirect the patient to second-line options.
      This fact underscores the need for advanced radiologic techniques, like specific
      diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to
      play a role in distinguishing these phenomena.

PMID- 29218628
TI  - Note from the SBIC President.

PMID- 29218627
TI  - Top ten errors of statistical analysis in observational studies for cancer
      research.
AB  - Observational studies using registry data make it possible to compile quality
      information and can surpass clinical trials in some contexts. However, data
      heterogeneity, analytical complexity, and the diversity of aspects to be taken
      into account when interpreting results makes it easy for mistakes to be made and
      calls for mastery of statistical methodology. Some questionable research
      practices that include poor analytical data management are responsible for the
      low reproducibility of some results; yet, there is a paucity of information in
      the literature regarding specific statistical pitfalls of cancer studies. In
      addition to proposing how to avoid or solve them, this article seeks to expose
      ten common problematic situations in the analysis of cancer registries:
      convenience, dichotomization, stratification, regression to the mean, impact of
      sample size, competing risks, immortal time and survivor bias, management of
      missing values, and data dredging.

PMID- 29218629
TI  - Design of artificial metalloproteins/metalloenzymes by tuning noncovalent
      interactions.
AB  - Noncovalent weak interactions [hydrophobic interaction and hydrogen (H)-bond]
      play crucial roles in controlling the functions of biomolecules, and thus have
      been used to design artificial metalloproteins/metalloenzymes during the past few
      decades. In this review, we focus on the recent progresses in protein design by
      tuning the noncovalent interactions, including hydrophobic and H-bonding
      interactions. The topics include redesign and reuse of the heme pocket and other
      protein scaffolds, design of the heme protein interface, and de novo design of
      metalloproteins. The informations not only give insights into the metalloenzyme
      reaction mechanisms but also provide new reactions for future applications.

PMID- 29218630
TI  - Differential reactivity of closely related zinc(II)-binding metallothioneins from
      the plant Arabidopsis thaliana.
AB  - The dynamics of metal binding to and transfer from metalloproteins involved in
      metal homeostasis are important for understanding cellular distribution of metal
      ions. The dicotyledonous plant Arabidopsis thaliana has two type 4 seed-specific
      metallothionein homologues, MT4a and MT4b, with likely roles in zinc(II)
      homeostasis. These two metallothioneins are 84% identical, with full conservation
      of all metal-binding cysteine and histidine residues. Yet, differences in their
      spatial and temporal expression patterns suggested divergence in their biological
      roles. To investigate whether biological functions are reflected in molecular
      properties, we compare aspects of zinc(II)-binding dynamics of full-length MT4a
      and MT4b, namely the pH dependence of zinc(II) binding and protein folding, and
      zinc(II) transfer to the chelator EDTA. UV-Vis and NMR spectroscopies as well as
      native electrospray ionisation mass spectrometry consistently showed that
      transfer from Zn6MT4a is considerably faster than from Zn6MT4b, with pseudo-first
      order rate constants for the fastest observed step of k obs = 2.8 * 10-4 s-1
      (MT4b) and k obs = 7.5 * 10-4 s-1 (MT4a) (5 uM protein, 500 uM EDTA, 25 mM Tris
      buffer, pH 7.33, 298 K). 2D heteronuclear NMR experiments allowed locating the
      most labile zinc(II) ions in domain II for both proteins. 3D homology models
      suggest that reactivity of this domain is governed by the local environment
      around the mononuclear Cys2His2 site that is unique to type 4 MTs. Non
      conservative amino acid substitutions in this region affect local electrostatics
      as well as whole-domain dynamics, with both effects rendering zinc(II) ions bound
      to MT4a more reactive in metal transfer reactions. Therefore, domain II of MT4a
      is well suited to rapidly release its bound zinc(II) ions, in broad agreement
      with a previously suggested role of MT4a in zinc(II) transport and delivery to
      other proteins.

PMID- 29218631
TI  - Intracellular metal binding and redox behavior of human DJ-1.
AB  - DJ-1 is a conserved, ubiquitous protein associated to a large number of
      intracellular processes. Human DJ-1 has been linked to several pathologies,
      including hereditary forms of Parkinson's disease, cancer, and amyotrophic
      lateral sclerosis. Several cytoprotective functions of DJ-1 have been reported,
      however, its actual mechanisms of action remain elusive. In vitro, DJ-1 has been
      shown to bind zinc and copper(II) at its active site, which contains a conserved
      cysteine (C106), and copper(I) at a different binding site. C106 is essential to
      DJ-1 function, and is easily oxidized upon oxidative stress. Here, we
      investigated the metal-binding- and redox properties of DJ-1 in living human
      cells by in-cell NMR. Intracellular DJ-1 is surprisingly free from interactions
      with any other cellular components and as such is clearly detectable by NMR.
      Metal-bound forms of DJ-1 were not observed upon treating the cells with excess
      zinc or copper. No copper binding was observed when co-expressing DJ-1 with the
      copper chaperone for superoxide dismutase 1 (SOD1). Co-expression of DJ-1 with
      SOD1 itself did not promote copper binding to SOD1, excluding a previously
      suggested function of DJ-1 as a copper chaperone. Overall, our data do not
      support the role of DJ-1 as a metalloprotein. Conversely, oxidative treatment to
      the cells caused the complete and selective oxidation of C106 to sulfinic acid,
      consistent with the reported role of DJ-1 as a redox sensor.

PMID- 29218632
TI  - Further insights into the metal ion binding abilities and the metalation pathway
      of a plant metallothionein from Musa acuminata.
AB  - The superfamily of metallothioneins (MTs) combines a diverse group of
      metalloproteins, sharing the characteristics of rather low molecular weight and
      high cysteine content. The latter provides MTs with the capability to coordinate
      thiophilic metal ions, in particular those with a d 10 electron configuration.
      The sub-family of plant MT3 proteins is only poorly characterized and there is a
      complete lack of three-dimensional structure information. Building upon our
      previous results on the Musa acuminata MT3 (musMT3) protein, the focus of the
      present work is to understand the metal cluster formation process, the role of
      the single histidine residue present in musMT3, and the metal ion binding
      affinity. We concentrate our efforts on the coordination of ZnII and CdII ions,
      using CoII as a spectroscopic probe for ZnII binding. The overall protein-fold is
      analysed with a combination of limited proteolytic digestion, mass spectrometry,
      and dynamic light scattering. Histidine coordination of metal ions is probed with
      extended X-ray absorption fine structure spectroscopy and CoII titration
      experiments. Initial experiments with isothermal titration calorimetry provide
      insights into the thermodynamics of metal ion binding.

PMID- 29218633
TI  - Characterization of the one-electron oxidized Cu(II)-salen complexes with a side
      chain aromatic ring: the effect of the indole ring on the Cu(II)-phenoxyl radical
      species.
AB  - To gain insights into the role of the proximal indole ring in the redox-active
      metal center as seen in galactose oxidase, we prepared the Cu(II)-salen-type
      complexes having a pendent indol-3-ylmethyl (1), methyl (2) or benzyl (3) group
      substituted on the ethylenediamine moiety and investigated the structures and
      redox properties by various physicochemical methods and theoretical calculations.
      Neutral complexes 1, 2, and 3 showed no significant difference in the UV-Vis-NIR
      and EPR spectra. One-electron oxidation of 1, 2, and 3 by addition of 1 equiv. of
      thianthrenyl radical gave [1]SbCl 6 , [2]SbCl 6 , and [3]SbCl 6 , respectively,
      which could be assigned to relatively localized phenoxyl radical species. The
      cyclic and differential pulse voltammograms of [1]SbCl 6 showed two redox waves
      with a large separation between the first and second redox potentials compared
      with the separations observed for [2]SbCl 6 and [3]SbCl 6 . This suggests that
      [1]SbCl 6 is more stabilized than [2]SbCl 6 and [3]SbCl 6 . The NIR band of
      [1]SbCl 6 showed a larger blue shift than that of [2]SbCl 6 and [3]SbCl 6 . The
      EPR spectrum of [2]SbCl 6 exhibited an intense signal at the g value of 2 due to
      partial disproportionation to form the EPR active two-electron oxidized complex
      [2] 2+ , while the EPR intensity of [1]SbCl 6 was much weaker than that of
      [2]SbCl 6 . These results indicate that the pendent indole moiety stabilizes the
      Cu(II)-phenoxyl radical in [1]SbCl 6 most probably by stacking with the phenoxyl
      moiety, which is further supported by DFT calculations.

PMID- 29218634
TI  - Walking the seven lines: binuclear copper A in cytochrome c oxidase and nitrous
      oxide reductase.
AB  - The enzymes nitrous oxide reductase (N2OR) and cytochrome c oxidase (COX) are
      constituents of important biological processes. N2OR is the terminal reductase in
      a respiratory chain converting N2O to N2 in denitrifying bacteria; COX is the
      terminal oxidase of the aerobic respiratory chain of certain bacteria and
      eukaryotic organisms transforming O2 to H2O accompanied by proton pumping.
      Different spectroscopies including magnetic resonance techniques, were applied to
      show that N2OR has a mixed-valent Cys-bridged [Cu1.5+(CyS)2Cu1.5+] copper site,
      and that such a binuclear center, called CuA, does also exist in COX. A sequence
      motif shared between the CuA center of N2OR and the subunit II of COX raises the
      issue of a putative evolutionary relationship of the two enzymes. The suggestion
      of a binuclear CuA in COX, with one unpaired electron delocalized between two
      equivalent Cu nuclei, was difficult to accept originally, even though regarded as
      a clever solution to many experimental observations. This minireview in honor of
      Helmut Sigel traces several of the critical steps forward in understanding the
      nature of CuA in N2OR and COX, and discusses its unique electronic features to
      some extent including the contributions made by the development of methodology
      and the discovery of a novel multi-copper enzyme. Left: X-band (9.130 GHz) and C
      band (4.530 GHz, 1st harmonic display of experimental spectrum) EPR spectra of
      bovine heart cytochrome c oxidase, recorded at 20K. Right: Ribbon presentation of
      the CuA domain in cytochrome c oxidase and nitrous oxide reductase.

PMID- 29218635
TI  - Long-range paramagnetic NMR data can provide a closer look on metal coordination
      in metalloproteins.
AB  - Paramagnetic NMR data can be profitably incorporated in structural refinement
      protocols of metalloproteins or metal-substituted proteins, mostly as distance or
      angle restraints. However, they could in principle provide much more information,
      because the magnetic susceptibility of a paramagnetic metal ion is largely
      determined by its coordination sphere. This information can in turn be used to
      evaluate changes occurring in the coordination sphere of the metal when ligands
      (e.g.: inhibitors) are bound to the protein. This gives an experimental handle on
      the molecular structure in the vicinity of the metal which falls in the so-called
      blind sphere. The magnetic susceptibility anisotropy tensors of cobalt(II) and
      nickel(II) ions bound to human carbonic anhydrase II in free and inhibited forms
      have been determined. The change of the magnetic susceptibility anisotropy is
      directly linked to the binding mode of different ligands in the active site of
      the enzyme. Indication about the metal coordination sphere in the presence of an
      inhibitor in pharmaceutically relevant proteins could be important in the design
      of selective drugs with a structure-based approach.

PMID- 29218636
TI  - Incorporation of second coordination sphere D-amino acids alters Cd(II)
      geometries in designed thiolate-rich proteins.
AB  - We use a de Novo protein design strategy to demonstrate that the second
      coordination sphere of a metal site plays a key role in controlling coordination
      geometries of Cd(II)-tris-thiolate complexes. Specifically, we show that
      alteration of chirality within the core hydrophobic packing region of a three
      stranded coiled coil (3SCC) can control the coordination number of Cd(II) by
      limiting steric encumbrance to the metal center. Within a specific class of 3SCCs
      [Ac-G-(LKALEEK) n -G-NH2], where n = 4 is TRI and n = 5 is GRAND, one L-Leu may
      be substituted by L-Cys to generate a planar tris-thiolate array capable of metal
      binding. In the native peptide containing only the L-configuration of leucine,
      the three-Cys ligand site leads to a mixture of 3- and 4-coordinate Cd(II). When
      the L-Leu above (toward the N-terminus) the tris-Cys site is substituted with D
      Leu, solely a 3-coordinate structure [Cd(II)S3] was obtained. When D-Leu is
      located below (toward the C-terminus), a mixture of two coordination geometries,
      presumably Cd(II)S3O and Cd(II)S3O2, is observed, while substitution with D-Leu
      both above and below the tris-Cys plane yields a higher percentage of 4
      coordinate Cd(II)S3O species. Thus, the use of D-amino acids around a metal's
      coordination sphere provides a powerful tool for controlling the properties of
      future designed metalloproteins.

PMID- 29218638
TI  - Celebrating Helmut Sigel.

PMID- 29218637
TI  - Specific phosphorothioate substitution within domain 6 of a group II intron
      ribozyme leads to changes in local structure and metal ion binding.
AB  - Group II introns are large self-splicing ribozymes that require high amounts of
      monovalent and divalent metal ions for folding and catalysis under in vitro
      conditions. Domain 6 of these ribozymes contains a highly conserved adenosine
      whose 2'-OH acts as a nucleophile during self-cleavage via the branching pathway.
      We have previously suggested a divalent metal ion that binds to the major groove
      at the GU wobble pair above the branch-A in a minimal, but active branch domain
      construct (D6-27) from the yeast mitochondrial intron Sc.ai5gamma. Here we
      characterize metal ion binding to the phosphate oxygens at the branch site. In
      vitro transcription yielded a D6-27 construct where all R P oxygens of the
      uridine phosphate groups are replaced by sulfur (alpha-thio-D6-27). We determined
      its NMR structure, the second RNA-only structure containing thiophosphate groups.
      [31P] resonances were assigned and chemical shift changes monitored upon
      titration with Cd2+. In addition, the two uridines flanking the branch-point, U19
      and U21 were specifically thioated by chemical synthesis (thio-U19-D6-27 and thio
      U19/U21-D6-27), enabling us to study Cd2+ binding at the R P-, as well as the S P
      position of the corresponding phosphate oxygens. Our studies reveal that both
      non-bridging phosphate oxygens of U19 are involved in metal ion coordination,
      whereas only the major groove phosphate oxygen of U21 is influenced. Together
      with NOE data of a hexaamminecobalt(III) titration, this suggests a single metal
      ion binding site at the GU wobble pair above the branch point in the major groove
      of D6 of this group II intron ribozyme.

PMID- 29218639
TI  - Histidine tracts in human transcription factors: insight into metal ion
      coordination ability.
AB  - Consecutive histidine repeats are chosen both by nature and by molecular
      biologists due to their high affinity towards metal ions. Screening of the human
      genome showed that transcription factors are extremely rich in His tracts. In
      this work, we examine two of such His-rich regions from forkhead box and MAFA
      proteins-MB3 (contains 18 His) and MB6 (with 21 His residues), focusing on the
      affinity and binding modes of Cu2+ and Zn2+ towards the two His-rich regions. In
      the case of Zn2+ species, the availability of imidazole nitrogen donors enhances
      metal complex stability. Interestingly, an opposite tendency is observed for Cu2+
      complexes at above physiological pH, in which amide nitrogens participate in
      binding.

PMID- 29218640
TI  - Oxoiron(IV) complexes as synthons for the assembly of heterobimetallic centers
      such as the Fe/Mn active site of Class Ic ribonucleotide reductases.
AB  - Nonheme oxoiron(IV) complexes can serve as synthons for generating
      heterobimetallic oxo-bridged dimetal complexes by reaction with divalent metal
      complexes. The formation of FeIII-O-CrIII and FeIII-O-MnIII complexes is
      described herein. The latter complexes may serve as models for the FeIII-X-MnIII
      active sites of an emerging class of Fe/Mn enzymes represented by the Class 1c
      ribonucleotide reductase from Chlamydia trachomatis and the R2-like ligand
      binding oxidase (R2lox) found in Mycobacterium tuberculosis. These synthetic
      complexes have been characterized by UV-Vis, resonance Raman, and X-ray
      absorption spectroscopy, as well as electrospray mass spectrometry. The FeIII-O
      CrIII complexes exhibit a three-band UV-Vis pattern that differs from the simpler
      features associated with FeIII-O-FeIII complexes. The positions of these features
      are modulated by the nature of the supporting polydentate ligand on the iron
      center, and their bands intensify dramatically in two examples upon the binding
      of an axial cyanate or thiocyanate ligand trans to the oxo bridge. In contrast,
      the FeIII-O-MnIII complexes resemble FeIII-O-FeIII complexes more closely.
      Resonance Raman characterization of the FeIII-O-MIII complexes reveals an 18O
      sensitive vibration in the range of 760-890 cm-1. This feature has been assigned
      to the asymmetric FeIII-O-MIII stretching mode and correlates reasonably with the
      Fe-O bond distance determined by EXAFS analysis. The likely binding of an acetate
      as a bridging ligand to the FeIII-O-MnIII complex 12 lays the foundation for
      further efforts to model the heterobimetallic active sites of Fe/Mn enzymes.

PMID- 29218641
TI  - Mixed guanine, adenine base quartets: possible roles of protons and metal ions in
      their stabilization.
AB  - Structural variations of the well-known guanine quartet (G4) motif in nucleic
      acid structures, namely substitution of two guanine bases (G) by two adenine (A)
      nucleobases in mutual trans positions, are discussed and studied by density
      functional theory (DFT) methods. This work was initiated by three findings,
      namely (1) that GA mismatches are compatible with complementary pairing patterns
      in duplex-DNA structures and can, in principle, be extended to quartet
      structures, (2) that GA pairs can come in several variations, including with a N1
      protonated adeninium moiety (AH), and (3) that cross-linking of the major donor
      sites of purine nucleobases (N1 and N7) by transition metal ions of linear
      coordination geometries produces planar purine quartets, as demonstrated by some
      of us in the past. Here, possible structures of mixed AGAG quartets both in the
      presence of protons and alkali metal ions are discussed, and in particular, the
      existence of a putative four-purine, two-metal motif.

PMID- 29218642
TI  - Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial
      activity.
AB  - A new water-soluble photocatalyst for singlet oxygen generation is presented. Its
      absorption extends to the red part of the spectrum, showing activity up to
      irradiation at 660 nm. Its efficiency has been compared to that of a commercial
      analogue (Rose Bengal) for the oxidation of L-methionine. The quantitative and
      selective oxidation was promising enough to encapsulate the photocatalyst in
      polymersomes. The singlet oxygen generated in this way can diffuse and remain
      active for the oxidation of L-methionine outside the polymeric compartment. These
      results made us consider the use of these polymersomes for antimicrobial
      applications. E. coli colonies were subjected to oxidative stress using the
      photocatalyst-polymersome conjugates and nearly all the colonies were damaged
      upon extensive irradiation while under the same red LED light irradiation, liquid
      cultures in the absence of porphyrin or porphyrin-loaded polymersomes were
      unharmed.

PMID- 29218643
TI  - Case Presentation Commentary on "Deciding wisely: A case for an effective use of
      myocardial perfusion imaging".

PMID- 29218645
TI  - Trajectories of Italian Children's Peer Rejection: Associations with Aggression,
      Prosocial Behavior, Physical Attractiveness, and Adolescent Adjustment.
AB  - In the present study, the predictors and outcomes associated with the
      trajectories of peer rejection were examined in a longitudinal sample of Italian
      children (338 boys, 269 girls) ages 10 to 14 years. Follow-up assessments
      included 60% of the original sample at age 16-17. Low, medium, and high rejection
      trajectory groups were identified using growth mixture models. Consistent with
      previous studies, we found that (a) being less prosocial and more physically
      aggressive at age 10 was characteristic of those children with the high rejection
      trajectory; (b) being less attractive was related to higher peer rejection from
      age 10 to 14; and (c) boys with a high rejection trajectory showed high levels of
      delinquency and anxiety-depression and low levels of academic aspiration at age
      16-17, whereas girls with a high rejection trajectory showed low levels of
      academic aspiration and social competence at age 16-17. Our findings indicate the
      detrimental consequences of peer rejection on children's development and
      adjustment and shed light on the mechanisms that contribute to maintaining or
      worsening (e.g., being attractive, prosocial, and aggressive) a child's negative
      status (e.g., being rejected) within his or her peer group over time.

PMID- 29218644
TI  - Cardiovascular Complications of Marijuana and Related Substances: A Review.
AB  - The recreational use of cannabis has sharply increased in recent years in
      parallel with its legalization and decriminalization in several countries.
      Commonly, the traditional cannabis has been replaced by potent synthetic
      cannabinoids and cannabimimetics in various forms. Despite overwhelming public
      perception of the safety of these substances, an increasing number of serious
      cardiovascular adverse events have been reported in temporal relation to
      recreational cannabis use. These have included sudden cardiac death, vascular
      (coronary, cerebral and peripheral) events, arrhythmias and stress cardiomyopathy
      among others. Many of the victims of these events are relatively young men with
      few if any cardiovascular risk factors. However, there are reasons to believe
      that older individuals and those with risk factors for or established
      cardiovascular disease are at even higher danger of such events following
      exposure to cannabis. The pathophysiological basis of these events is not fully
      understood and likely encompasses a complex interaction between the active
      ingredients (particularly the major cannabinoid, Delta9-tetrahydrocannabinol),
      and the endo-cannabinoid system, autonomic nervous system, as well as other
      receptor and non-receptor mediated pathways. Other complicating factors include
      opposing physiologic effects of other cannabinoids (predominantly cannabidiol),
      presence of regulatory proteins that act as metabolizing enzymes, binding
      molecules, or ligands, as well as functional polymorphisms of target receptors.
      Tolerance to the effects of cannabis may also develop on repeated exposures at
      least in part due to receptor downregulation or desensitization. Moreover,
      effects of cannabis may be enhanced or altered by concomitant use of other
      illicit drugs or medications used for treatment of established cardiovascular
      diseases. Regardless of these considerations, it is expected that the current
      cannabis epidemic would add significantly to the universal burden of
      cardiovascular diseases.

PMID- 29218646
TI  - Cardiovascular and Metabolic Complications - Diagnosis and Management in Obese
      Children.
AB  - The world at present is facing a burden of rising prevalence of obesity in
      children and adolescents. The developing countries are particularly facing the
      dual burden on under-nutrition and obesity. This is associated with appearance
      and clustering of cardiometabolic abnormalities at an early age with development
      of chronic complications early and possible decrease in life span of these
      children and adolescents. In adults this clustering has been termed as 'metabolic
      syndrome' with definitions that can be used universally. However, in children and
      adolescents there is no consensus on a uniform definition of metabolic syndrome
      that can be applicable across the age groups and various ethnicities. Further, as
      childhood is a period of growth and development, changes in body composition and
      insulin sensitivity that occur with puberty may influence the thresholds of
      components used to define metabolic syndrome. Children of South Asian ethnicity
      appear to be more predisposed to develop abnormalities of metabolic syndrome,
      possible due to their adverse body fat patterning and genetic influences. The
      definition of pediatric metabolic syndrome proposed by International Diabetes
      Federation is useful across different ethnicities. Presence of at least one
      component of metabolic syndrome should lead to detailed screening for other
      components and complications. A multimodality approach including therapeutic
      lifestyle changes targeted at the individual, family and community is essential
      for management. Pharmacotherapy for individual components may be required if
      initial management strategies fail to achieve the goals.

PMID- 29218648
TI  - Pelvic fracture instability-associated L5 transverse process fracture, fact or
      myth? A systematic review and meta-analysis.
AB  - PURPOSE: Stable or unstable pelvic ring fractures are sometimes associated with
      L5 transverse process (TP) fractures. This review aimed to determine the effect
      of L5 TP fractures on pelvic ring fracture stability. METHODS: We searched
      electronic databases (including MEDLINE, Google Scholar, and SCOPUS) and
      performed hand searching of English orthopedics journals and conference abstracts
      until May 2017. We pooled data from five studies, with a total of 278 patients.
      RESULTS: Of 28 studies, five were included (four studies involved adult patients,
      one pediatric population). Of the 278 pelvic fractures (average age 37.33 years;
      male 132 and female 92), 99 (35.6%) were stable and 179 (64.4%) were unstable
      (fracture B and C, according to the Tile classification). Sixty-seven (24.1%)
      were cases with L5 TP, and 211 (75.9%) were cases without L5 TP fracture. The
      typical causes of injury were road traffic accident (59.2%), fall from height
      (23.6%), and crush injuries and injuries by heavy objects (17.2%). The pooled
      odds ratio (OR) of L5 TP between the stable and unstable groups calculated with
      random effect analysis was 0.418 (0.083-2.108; p = 0.291); after excluding the
      study on a pediatric population, the pooled OR was 0.349 (0.056-2.159; p =
      0.258). CONCLUSIONS: L5 TP fractures may indicate high-energy trauma; however, no
      relationship between L5 TP fractures and pelvic ring fracture stability exists.
      LEVEL OF EVIDENCE: Prognostic Level IV.

PMID- 29218649
TI  - Treatment of flexor tendon reconstruction failures: multicentric experience with
      Brunelli active tendon implant.
AB  - INTRODUCTION: Secondary repair of flexor tendon injuries remain a challenging
      procedure for hand surgeons. Usually, secondary reconstruction should be
      performed by staged approach. When the tendon and pulley integrity are intact,
      tenolysis may be the first surgical option. One-/two-stage tendon grafts are
      suggested when the integrity of flexor tendon is compromised. Active tendon
      implants (Brunelli prostheses) may represent an efficient option in patients with
      a poor prognosis, as well as whenever classical techniques fail. Due to lack of
      literature about this second-line treatment, the authors present the experience
      of two different orthopedic departments with the permanent active tendon implant.
      MATERIALS AND METHOD: Nineteen consecutive patients with failed previous flexor
      tendons repairs were treated with active tendon implants between 2000 and 2011.
      The functional outcome of the patients was examined with a mean follow-up of 5.6
      years, using Strickland assessment and QuickDASH. RESULTS: In 16 cases, the
      tendon implants were well tolerated and patients resulted satisfied with a
      QuickDASH score less than 33. Strickland score was fair to excellent in 10
      patients. We registered adhesion complications in 3 cases. CONCLUSION: We can
      conclude that these prostheses represent an alternative to biological
      reconstructions and a potentially permanent procedure in complicated flexor
      tendon injuries. LEVEL OF EVIDENCE: Multicentric case series, Level IV.

PMID- 29218650
TI  - Structural Characterization and In Vitro Antitumor Activity of a Novel
      Exopolysaccharide from Lachnum YM130.
AB  - Exopolysaccharide of Lachnum YM130 (LEP) was purified by diethylaminoethyl
      cellulose 52 and Sepharose CL-6B column chromatography. LEP-2a was identified to
      be a homogeneous component with an average molecular weight of 1.31 * 106 Da,
      which was consisted of mannose and galactose in a molar ratio of 3.8:1.0. The
      structure of LEP-2a was characterized by methylation analysis, FT-IR analysis,
      and NMR analysis. Results indicated that LEP-2a was a galactomannan with a
      backbone, composed of 1,2-linked-alpha-D-Manp, 1,2,6-linked-alpha-D-Manp, 1,3,4
      linked-alpha-D-Manp, and 1,3-linked-beta-D-Galp, which was substituted at O-2, O
      3, O-4, and O-6 by branches. In vitro antitumor activity assay proved that LEP-2a
      could significantly enhance the inhibitory effectiveness of 5-FU on Hela cells at
      the concentrations of 100, 200, 300, and 400 MUg/mL. The above results suggested
      that LEP-2a could be seen as a potential source for developing novel
      antineoplastic agents.

PMID- 29218651
TI  - Increasing hip fracture rates among older adults in Ecuador: analysis of the
      National Hospital Discharge System, 1999-2016.
AB  - : The Ecuadorian hospital discharge system examined trends in hip fracture
      hospitalization rates among older adults. A significant upward trend in hip
      fracture rates occurred in both genders over the study period. INTRODUCTION:
      Previous research has reported increasing hip fracture rates in Ecuador. Thus,
      this study aimed to extend previous findings by examining the nationwide
      incidence of hip fractures among adults aged 65 years and older between 1999 and
      2016. A secondary objective was to compare hip fracture trends among older
      Ecuadorians with their counterparts in the United States (U.S.). METHODS: The
      National Hospital Discharge System and the Healthcare Cost and Utilization
      Project net were assessed to identify older adults hospitalized with a principal
      diagnosis of hip fractures in Ecuador and the U.S., respectively. The Joinpoint
      regression analysis software was used to examine the average annual percent
      change in hip fracture rates. RESULTS: A total of 20,091 adults with a mean age
      of 82.3 (SD 8.1) years were hospitalized with a principal diagnosis of hip
      fractures during the study period. After an adjustment for age, hip fracture
      rates increased annually on average by 4.6% (95% CI 3.8%, 5.4%) from 96.4/100,000
      in 1999 to 173.1/100,000 persons in 2016. Between 1999 and 2014, hip fracture age
      adjusted rates decreased on average by - 2.5% (95% CI - 2.7%, - 2.3%) among older
      adults in the U.S. while hip fracture rates steadily increased by 4.6% (95% CI,
      3.6%, 5.7%) per year in their Ecuadorian counterparts. CONCLUSIONS: Hip fracture
      rates markedly increased among older adults in Ecuador. The present findings
      should alert public health authorities to implement policies of osteoporosis
      awareness and prevention in Ecuador.

PMID- 29218652
TI  - Metastasis suppressor 1 (MTSS1) expression is associated with reduced in-vivo
      metastasis and enhanced patient survival in lung adenocarcinoma.
AB  - Metastasis suppressor 1 (MTSS1) has been shown to be a metastasis suppressor in a
      number of cancers. However, its role in lung adenocarcinoma is largely unknown.
      To evaluate the significance of MTSS1 expression on lung adenocarcinoma
      metastatic properties, the gain or loss of MTSS1 in in vivo and in vitro
      experiments were employed. Using an in vivo orthotopic mouse xenograft model
      mimicking human disease progression, stable overexpression of MTSS1 in lung
      adenocarcinoma cells resulted in a significant decrease in metastatic burden.
      Stable overexpression of MTSS1 in NCI-H1299 decreased in vitro lung
      adenocarcinoma invasion and migration while knockdown of MTSS1 in A549 resulted
      in a significant increase in cell invasion and migration. Using The Cancer Genome
      Atlas dataset of over 500 patient lung adenocarcinoma specimens, we demonstrated
      a 20% increase in 5-year survival associated with preserved intratumoral MTSS
      expression. MTSS1 expression in lung adenocarcinoma is associated with decreased
      metastatic burden, as assessed by an in vivo orthotopic model, and correlates
      with a 20% survival advantage at 5 years following diagnosis. In vitro data
      suggests MTSS1 regulates lung adenocarcinoma through augmentation of cell
      invasion and migration.

PMID- 29218653
TI  - Differential Diagnosis of Pancreatic Epidermoid Cyst Without a Solid Component
      (Residual Splenic Tissue) vs. Mucinous Cystic Neoplasm.
AB  - PURPOSE: The purpose of this study was to clarify whether there are differences
      in imaging findings between pancreatic epidermoid cyst (EDC) without a solid
      component (residual splenic tissue) and mucinous cystic neoplasm (MCN). MATERIALS
      AND METHODS: The study group consisted of histologically proven EDC (eight cases)
      and MCN (20 cases). CT and MRI findings were compared on the following imaging
      findings: the shape of the cystic lesions and the presence or absence of septum,
      calcification, and high-intensity fluid on T1- and diffusion-weighted images (b
      factor = 1000). The degree of contact with the pancreatic tail was compared
      between the EDCs and six of the MCNs at the edge of the pancreatic tail. RESULTS:
      The EDCs were round (n = 3) or oval (n = 5), while the MCNs consisted of three
      round, five oval, six pear-like, and six multilobulated lesions (P < 0.05).
      Septum was present in 4 of 8 (50%) EDCs and 19 of 20 (95%) MCNs (P < 0.05). The
      presence of calcification (2 of 8 [25%] EDCs vs. 8 of 20 [40%] MCNs), high
      intensity fluid on T1-weighted images (2 of 7 [29%] EDCs vs. 5 of 20 [25%] MCNs),
      and high-intensity fluid on diffusion-weighted images (5 of 7 [71%] EDCs vs. 5 of
      20 [25%] MCNs) were not significantly different. The degree of contact with the
      pancreatic parenchyma was similar between the two types of lesions. CONCLUSION:
      Although the imaging findings for EDC without a solid component and MCN overlap,
      a pear-like or multilobulated shape may favor a diagnosis of MCN.

PMID- 29218654
TI  - miR-200c as a Predictive Biomarker for 5-Fluorouracil Chemosensitivity in
      Colorectal Cancer.

PMID- 29218655
TI  - A Rare Case of a Metastatic Gastrointestinal Stromal Tumor (GIST): a Case Report
      and Review of the Literature.

PMID- 29218656
TI  - Multipath Curved Planar Reformations of Peripheral CT Angiography: Diagnostic
      Accuracy and Time Efficiency.
AB  - OBJECTIVES: To compare diagnostic performance and time efficiency between 3D
      multipath curved planar reformations (mpCPRs) and axial images of CT angiography
      for the pre-interventional assessment of peripheral arterial disease (PAD), with
      digital subtraction angiography as the standard of reference. METHODS: Forty
      patients (10 females, mean age 72 years), referred to CTA prior to endovascular
      treatment of PAD, were prospectively included and underwent peripheral CT
      angiography. A semiautomated toolbox was used to render mpCPRs. Twenty-one
      arterial segments were defined in each leg; for each segment, the presence of
      stenosis > 70% was assessed on mpCPRs and axial images by two readers,
      independently, with digital subtraction angiography as gold standard. RESULTS:
      Both readers reached lower sensitivity (Reader 1: 91 vs. 94%, p = 0.08; Reader 2:
      89 vs. 93%, p = 0.03) but significantly higher specificity (Reader 1: 94 vs. 89%,
      p < 0.01; Reader 2: 96 vs. 95%, p = 0.01) with mpCPRs than with axial images.
      Reader 1 achieved significantly higher accuracy with mpCPRs (93 vs. 91%, p =
      0.02), and Reader 2 had similar overall accuracy in both evaluations (94 vs. 94%,
      p = 0.96). Both readers read mpCPRs significantly faster than axial images
      (Reader 1: 5'45" based on mpCPRs vs. 7'40" based on axial images; Reader 2: 4'41"
      based on mpCPRs vs. 6'57" based on axial images; p < 0.01). CONCLUSIONS: mpCPRs
      are a promising 3D reformation technique that facilitates a fast assessment of
      PAD with high diagnostic accuracy.

PMID- 29218657
TI  - Comparison of laparoscopic jejunostomy tube to percutaneous endoscopic
      gastrostomy tube with jejunal extension: long-term durability and nutritional
      outcomes.
AB  - INTRODUCTION: Enteral access through the jejunum is indicated when patients
      cannot tolerate oral intake or gastric feeding. While multiple approaches for
      feeding jejunal access exist, few studies have compared the efficacy of these
      techniques. The purpose of this study was to investigate the long-term
      durability, re-intervention rates, and nutritional outcomes following
      percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET)
      versus laparoscopic jejunostomy tubes (j-tubes). METHODS: Retrospective chart
      review was performed on all patients who underwent PEG-JET or laparoscopic
      jejunostomy tube placement from January 2005 through December 2015 at our
      institution. Thirty-day and long-term outcomes were compared between the two
      groups. RESULTS: A total of 105 patients underwent PEG-JET and 307 patients
      underwent laparoscopic j-tube placement during the defined study period. In terms
      of 30-day outcomes, patients who underwent PEG-JET placement were significantly
      more likely to experience a tube dislodgement event (p = 0.005) and undergo a re
      intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were
      significantly more likely to meet their enteral feeding goals (p = 0.002) and
      less likely to require nutritional supplementation with total parenteral
      nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who
      underwent PEG-JET placement were significantly more likely to experience tube
      occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention
      (p < 0.001). Patients who underwent laparoscopic j-tube placement were
      significantly more likely to experience a tube site leak (p = 0.015) but were
      less likely to require nutritional supplementation with TPN (p = 0.001).
      CONCLUSION: Laparoscopic jejunostomy tubes provide more durable long-term enteral
      access compared to PEG-JET. Consideration should be given to laparoscopic
      jejunostomy tube placement in eligible patients who cannot tolerate oral intake
      or gastric enteral feeding.

PMID- 29218658
TI  - Hypopharyngeal multichannel intraluminal impedance leads to the promising outcome
      of antireflux surgery in Japanese population with laryngopharyngeal reflux
      symptoms.
AB  - BACKGROUND: Clinical characteristics of laryngopharyngeal reflux (LPR) in
      Japanese population remain unclear, and its treatment outcome is suboptimal. The
      objectives of this study were to evaluate Japanese patients with LPR symptoms
      using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the
      outcome of antireflux surgery (ARS). METHODS: Subjects included patients who had
      LPR symptoms for > 12 weeks or laryngoscopic findings suggestive of LPR and
      underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal
      exposure (APE) was defined as LPR >= 1/day and/or full column reflux (FCR)
      (reflux 2 cm distal to the upper esophageal sphincter) >= 5/day on HMII. Patients
      with APE were offered ARS and the outcome of ARS was objectively assessed using
      Reflux Symptom Index (RSI). RESULTS: From July 2015 to September 2016, 52
      patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII,
      and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI <
      25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third
      of LPR and FCR events were non-acid in the distal esophagus. A positive symptom
      association probability was seen only in 18 patients (35%). Mild esophagitis and
      hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12
      patients (100%) who had undergone ARS were able to discontinue PPI and had a
      significant improvement in the RSI scores postoperatively (22.9 +/- 10.0 vs. 6.8
      +/- 6.8, p < .001). CONCLUSIONS: APE was frequently observed in Japanese patients
      with LPR symptoms. Obesity and esophagitis were uncommon in this population.
      Since a large number of patients with APE had negative DeMeester score and
      proximal reflux events were often non-acid, a conventional pH monitoring is
      insufficient. HMII is crucial to evaluate patients with LPR symptoms as the
      documentation of APE is a key for successful outcome of ARS.

PMID- 29218659
TI  - Single-site robotic-assisted laparoscopic cholecystectomy in children and
      adolescents: a report of 20 cases.
AB  - BACKGROUND: Single-site laparoscopy is increasingly popular for straightforward
      operations like appendectomy. Due to limited triangulation and maneuverability,
      single-site cholecystectomy is riskier and more difficult. Robotics offer to make
      it easier and safer. METHODS: Twenty children and adolescents underwent robotic
      assisted single-site cholecystectomy at a large academic children's hospital.
      Patients were not randomized; patients were offered the option of robotic
      assisted single-site (SSR) or standard four-incision laparoscopic (LAP)
      cholecystectomy. Demographics and perioperative details were compared with those
      of a comparable cohort who underwent LAP during the same period. RESULTS: The two
      groups were similar in physical characteristics and indications for operation.
      The robotic operations took longer but both groups received similar PRN doses of
      parenteral opiates. Patients in the SSR group were all discharged on the first
      postoperative day. There were no major complications in either group but a
      slightly higher incidence of minor wound complications in the SSR group.
      CONCLUSION: Robotic-assisted single-site cholecystectomy appears to be a safe
      alternative to standard laparoscopy with a similar postoperative pain profile,
      short postoperative lengths of stay, and, for some, a superior cosmetic result.
      Nevertheless, it comes with longer set-up and operative times, a higher incidence
      of minor wound complications, an unknown but possibly higher risk of incisional
      hernia, and higher costs.

PMID- 29218660
TI  - How bariatric surgery affects liver volume and fat density in NAFLD patients.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an epidemic in the
      obese population. Bariatric surgery is known to reverse multiple metabolic
      complications of obesity such as diabetes, dyslipidemia, and NAFLD, but the
      timing of liver changes has not been well described. MATERIALS AND METHODS: This
      was an IRB-approved, two-institutional prospective study. Bariatric patients
      received MRIs at baseline and after a pre-operative liquid diet. Liver biopsies
      were performed during surgery and if NAFLD positive, the patients received MRIs
      at 1, 3, and 6 months. Liver volumes and proton-density fat fraction (PDFF) were
      calculated from offline MRI images. Primary outcomes were changes in weight, body
      mass index (BMI), percent excess weight loss (EWL%), liver volume, and PDFF.
      Resolution of steatosis, as defined as PDFF < 6.4% based on previously published
      cutoffs, was assessed. Secondarily, outcomes were compared between patients who
      underwent laparoscopic sleeve gastrectomy (LSG) versus laparoscopic Roux-en-Y
      gastric bypass (LRYGB). RESULTS: From October 2010 to June 2015, 124 patients
      were recruited. 49 patients (39.5%) completed all five scans. EWL% at 6 months
      was 55.6 +/- 19.0%. BMI decreased from 45.3 +/- 5.9 to 34.4 +/- 5.1 kg/m2 and
      mean liver volume decreased from 2464.6 +/- 619.4 to 1874.3 +/- 387.8 cm3 with a
      volume change of 21.4 +/- 11.4%. PDFF decreased from 16.6 +/- 7.8 to 4.4 +/-
      3.4%. At 6 months, 83.7% patients had resolution of steatosis. Liver volume
      plateaued at 1 month, but PDFF and BMI continued to decrease. There were no
      statistically significant differences in liver volume or PDFF reduction from
      baseline to 6 months between the LSG versus LRYGB subgroups. CONCLUSION: Patients
      with NAFLD undergoing bariatric surgery can expect significant decreases in liver
      volume and hepatic steatosis at 6 months, with 83.7% of patients achieving
      resolution of steatosis. Liver volume reduction plateaus 1-month post-bariatric
      surgery, but PDFF continues to decrease. LSG and LRYGB did not differ in efficacy
      for inducing regression of hepatosteatosis.

PMID- 29218662
TI  - Laparoscopic removal of retroperitoneal tumor with maneuver of hanging inferior
      vena cava.
AB  - BACKGROUND: Laparoscopic resection of retroperitoneal mass is challenging because
      of its location close to major vessels and a limited range of laparoscopic
      instruments [1-3]. We report a case of a huge retroperitoneal paraganglioma that
      was successfully excised laparoscopically using maneuver of hanging IVC METHOD: A
      67-year-old female had abdominal mass detected during routine check-up. She had
      no symptoms associated mass. Hematologic, biochemical investigations, and hormone
      tests reveal normal results. Preoperative CT shows retroperitoneal tumor,
      measuring 6.1 cm in diameter, which was closely adhered to right adrenal gland
      and seemed to originate from adrenal gland. Three 12-mm trocars and two 5-mm
      trocars were used. Laparoscopic views showed that severe adhesion in peritoneal
      cavity due to previous subtotal gastrectomy for gastric polyp about 30 years ago.
      After adhesiolysis, the mass was visualized behind inferior vena cava. The mass
      was carefully dissected and separated from duodenum and inferior vena cava as
      well as right adrenal gland. Inferior vena cava was retracted with hanging
      maneuver of IVC with vascular tape. The fibrotic tissues covering the mass were
      dissected with ligasureTM. The feeding vessels supplying mass were identified and
      clipped, then subsequently sealed and divided. After complete resection of mass,
      the specimen was inserted into plastic retrieval bag and extracted via extended
      umbilical port. And then Jackson Pratt drain was placed around inferior vena
      cava. RESULT: There was no intraoperative transfusion and complications during
      laparoscopic retroperitoneal excision for paraganglioma. The operation time was
      190 min, and estimated blood loss was 100 ml. The patient was discharged on
      postoperative 5th day without complications. Final pathologic result was
      paraganglioma of 7.5 cm sized with PASS score 4 (pheochromocytoma of the adrenal
      gland scaled score). CONCLUSION: Laparoscopic surgery for huge retroperitoneal
      paraganglioma behind IVC was successfully performed with the maneuver of hanging
      IVC. This procedure could be useful with appropriate laparoscopic technique and
      proper patient selection.

PMID- 29218661
TI  - The SAGES Fundamental Use of Surgical Energy program (FUSE): history,
      development, and purpose.
AB  - BACKGROUND: Adverse events due to energy device use in surgical operating rooms
      are a daily occurrence. These occur at a rate of approximately 1-2 per 1000
      operations. Hundreds of operating room fires occur each year in the United
      States, some causing severe injury and even mortality. The Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES) therefore created the first
      comprehensive educational curriculum on the safe use of surgical energy devices,
      called Fundamental Use of Surgical Energy (FUSE). This paper describes the
      history, development, and purpose of this important training program for all
      members of the operating room team. METHODS: The databases of SAGES and the FUSE
      committee as well as personal photographs and documents of members of the FUSE
      task force were used to establish a brief history of the FUSE program from its
      inception to its current status. RESULTS: The authors were able to detail all
      aspects of the history, development, and national as well as global
      implementation of the third SAGES Fundamentals Program FUSE. CONCLUSIONS: The
      written documentation of the making of FUSE is an important contribution to the
      history and mission of SAGES and allows the reader to understand the idea,
      concept, realization, and implementation of the only free online educational tool
      for physicians on energy devices available today. FUSE is the culmination of the
      SAGES efforts to recognize gaps in patient safety and develop state-of-the-art
      educational programs to address those gaps. It is the goal of the FUSE task force
      to ensure that general FUSE implementation becomes multinational, involving as
      many countries as possible.

PMID- 29218663
TI  - Laparoscopic extended cholecystectomy for T3 gallbladder cancer.
AB  - BACKGROUND: Gallbladder cancer (GBC) has been contraindicated for laparoscopic
      surgery since this procedure was introduced [1, 2]. Recently, however, there have
      been several reports of laparoscopic extended cholecystectomy for GBC, but most
      cases involved early GBC confined to the GB [3, 4]. This video describes our
      technique of laparoscopic extended cholecystectomy for T3 GBC. METHODS: A 77-year
      old female presented with a gallbladder mass, which was incidentally detected
      during evaluation of back pain. Abdominal computed tomography and endoscopic
      ultrasonography revealed a 3.5 * 2.5 cm hypoechoic mass in the gallbladder fundus
      with liver invasion. We performed laparoscopic en bloc resection of the
      gallbladder and the gallbladder bed, as well as lymphadenectomy. RESULTS: Two 5
      mm and three 12-mm trocars were used. After carefully dissecting Calot's
      triangle, the cystic duct was dissected and ligated. The cystic duct margin was
      negative on the frozen section biopsy. Cholecystectomy with en bloc wedge
      resection of the liver was performed first. Ultrasonic shears were used to
      transect the superficial hepatic parenchyma and a Cavitron Ultrasonic Surgical
      Aspirator was used to transect the deeper parenchyma. We then performed
      lymphadenectomy of involved lymph nodes (LNs) around the hepatoduodenal ligament,
      common hepatic artery, and posterior superior pancreas. After Kocherization of
      the duodenum, LNs were dissected from the posterior superior portion of the
      pancreas. LN dissection continued along the right side of the common bile duct
      and the portal vein. After dissection from the inferior vena cava and the aorta,
      the dissected LNs were pushed toward the left side under the portal vein. LN
      dissection continued along the left side of the hepatoduodenal ligament, while
      exposing the common hepatic artery and proper hepatic artery. Skeletonizing en
      bloc LN dissection was the final procedure. The operation time was 215 min and
      the estimated intraoperative blood loss was 200 mL. The postoperative pathology
      confirmed a small cell neuroendocrine carcinoma with clear resection margins. The
      pathologic staging was pT3N1. LN metastasis was found in one of 12 retrieved LNs.
      The patient was discharged on postoperative day 4 without postoperative
      complications. The patient received combined chemoradiation therapy for 6 months
      after surgery. There was no evidence of recurrence over the follow-up period of
      14 months. CONCLUSION: Laparoscopic extended cholecystectomy is technically
      feasible in patients with T3 GBC, and the extent of resection is the same as that
      of open surgery.

PMID- 29218664
TI  - Cost-effectiveness of per oral endoscopic myotomy relative to laparoscopic Heller
      myotomy for the treatment of achalasia.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) has recently emerged as a viable
      option relative to the classic approach of laparoscopic Heller myotomy (LHM) for
      the treatment of esophageal achalasia. In this cost-utility analysis of POEM and
      LHM, we hypothesized that POEM would be cost-effective relative to LHM. METHODS:
      A stochastic cost-utility analysis of treatment for achalasia was performed to
      determine the cost-effectiveness of POEM relative to LHM. Costs were estimated
      from the provider perspective and obtained from our institution's cost-accounting
      database. The measure of effectiveness was quality-adjusted life years (QALYs)
      which were estimated from direct elicitation of utility using a visual analog
      scale. The primary outcome was the incremental cost-effectiveness ratio (ICER).
      Uncertainty was assessed by bootstrapping the sample and computing the cost
      effectiveness acceptability curve (CEAC). RESULTS: Patients treated within an 11
      year period (2004-2016) were recruited for participation (20 POEM, 21 LHM).
      During the index admission, the mean costs for POEM ($8630 +/- $2653) and the
      mean costs for LHM ($7604 +/- $2091) were not significantly different (P =
      0.179). Additionally, mean QALYs for POEM (0.413 +/- 0.248) were higher than that
      associated with LHM (0.357 +/- 0.338), but this difference was also not
      statistically significant (P = 0.55). The ICER suggested that it would cost an
      additional $18,536 for each QALY gained using POEM. There was substantial
      uncertainty in the ICER; there was a 48.25% probability that POEM was cost
      effective at the mean ICER. At a willingness-to-pay threshold of $100,000, there
      was a 68.31% probability that POEM was cost-effective relative to LHM.
      CONCLUSIONS: In the treatment of achalasia, POEM appears to be cost-effective
      relative to LHM depending on one's willingness-to-pay for an additional QALY.

PMID- 29218665
TI  - Benefits of laparoscopic liver resection in patients with hepatocellular
      carcinoma and portal hypertension: a case-matched study.
AB  - BACKGROUND: The advantages of laparoscopy over open liver resection in patients
      with cirrhosis have been widely demonstrated. On the other hand, information on
      the role of minimally invasive liver surgery in the presence of clinically
      significant portal hypertension (CSPH) is scarce. The aim of this study was to
      evaluate the role of laparoscopic liver resection in selected cirrhotic patients
      with CSPH. METHODS: A retrospective case-control study of cirrhotic patients with
      hepatocellular carcinoma who were treated with laparoscopic liver resection was
      conducted from December 2005 to April 2016. A total of 45 patients were included.
      Patients were divided into two groups according to the presence or absence of
      clinically significant portal hypertension. Fifteen cirrhotic patients with CSPH
      were matched with 30 patients without CSPH. RESULTS: Overall, there were no
      differences in intraoperative results. No conversion to open surgery occurred in
      the CSPH group, and 3 patients were converted in the Non-CSPH group (0 vs. 10% p
      = 0.57). Only 2 (7%) patients in the Non-CSPH group and 1 (7%) in the CSPH group
      had relevant complications (modified Clavien-Dindo classification III). Two
      patients in the Non-CSPH group and one in the CSPH group developed transient
      ascites (7 vs. 7%). Postoperative hospital stay was similar in both groups, with
      a median of 4 days in the CSPH group and 3 days in the Non-CSPH group (p = 0.37).
      The median follow-up of the entire cohort was 38 months (range 7-100). Overall
      survival rates at 1 and 3 years were 100 and 87%, respectively. There was no
      significant difference between the groups in terms of survival (p = 0.8).
      CONCLUSION: This initial study showed that laparoscopic resection in patients
      with CSPH can be performed safely in well-selected patients and expand the
      current surgical indications in patients with CSPH. Prospective trials with a
      larger sample size are necessary to confirm these results.

PMID- 29218666
TI  - Transition from laparoscopic to retroperitoneoscopic approach for live donor
      nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy has become the standard of care due to
      multiple benefits. Currently, there are various techniques employed with two
      different approaches: transperitoneal (TLDN) or retroperitoneoscopic (RLDN)
      approach. There is a lack of data to determine which technique is superior,
      although the RLDN offers an anatomical advantage by avoidance of manipulation of
      the intraperitoneal organs. The aims of this study were to explore the merits of
      RLDN to TLDN and assess the learning curve of transition from TLDN to RLDN.
      METHODS: From January 2010 to February 2017, 106 live donor nephrectomies were
      performed: 56 by TLDN and 50 by RLDN. Data on patient demographics, perioperative
      parameters, analgesic consumption, pain scores, and kidney graft function were
      collected and analysed. Data were compared with a Student's t test or Mann
      Whitney test. A CUSUM analysis was performed to investigate the learning curve.
      RESULTS: All live donor nephrectomies were successful with no conversion to open
      surgery. There was no blood transfusion, readmission, or mortality. No
      postoperative complications were graded over Clavien II. Kidney function was
      comparable in both groups. The follow-up period ranged from 3 to 78 months.
      CONCLUSION: Retroperitoneoscopic live donor nephrectomy is a safe approach with
      comparable results to TLDN. RLDN has an anatomical advantage as it avoids
      manipulating the intraperitoneal organs and retains a virgin abdomen and hence
      translates to a lower perioperative complication risk.

PMID- 29218667
TI  - The NOVEL trial: natural orifice versus laparoscopic cholecystectomy-a
      prospective, randomized evaluation.
AB  - INTRODUCTION: The evolution of Natural Orifice Translumenal Endoscopic Surgery(r)
      (NOTES(r)) represents a case study in surgical procedural evolution. Beginning in
      2004 with preclinical feasibility studies, and followed by the creation of the
      NOSCAR(r) collaboration between The Society of American Gastrointestinal and
      Endoscopic Surgeons and the American Society for Gastrointestinal Endoscopy,
      procedural development followed a stepwise incremental pathway. The work of this
      consortium has included white paper analyses, obtaining outside independent
      funding for basic science and procedural development, and, ultimately, the
      initiation of a prospective randomized clinical trial comparing NOTES(r)
      cholecystectomy as an alternative procedure to laparoscopic cholecystectomy.
      METHODS: Ninety patients were randomized into a randomized clinical trial with
      the primary objective of demonstrating non-inferiority of the transvaginal and
      transgastric arms to the laparoscopic arm. In the original trial design, there
      were both transgastric and transvaginal groups to be compared to the laparoscopic
      control group. However, after enrollment and randomization of 6 laparoscopic
      controls and 4 transgastric cases into the transgastric group, this arm was
      ultimately deemed not practical due to lagging enrollment, and the arm was
      closed. Three transgastric via the transgastric approach were performed in total
      with 9 laparoscopic control cases enrolled through the TG arm. Overall a total of
      41 transvaginal and their 39 laparoscopic cholecystectomy controls were
      randomized into the study with 37 transvaginal and 33 laparoscopic
      cholecystectomies being ultimately performed. Overall total operating time was
      statistically longer in the NOTES(r) group: 96.9 (64.97) minutes versus 52.1
      (19.91) minutes. RESULTS: There were no major adverse events such as common bile
      duct injury or return to the operating room for hemorrhage. Intraoperative blood
      loss, length of stay, and total medication given in the PACU were not
      statistically different. There were no conversions in the NOTES(r) group to a
      laparoscopic or open procedure, nor were there any injuries, bile leaks,
      hemorrhagic complications, wound infections, or wound dehiscence in either group.
      There were no readmissions. Visual Analogue Scale (VAS) pain scores were 3.4 (CI
      2.82) in the laparoscopic group and 2.9 (CI 1.96) in the transvaginal group (p =
      0.41). The clinical assessment on cosmesis scores was not statistically different
      when recorded by clinical observers for most characteristics measured when the
      transvaginal group was compared to the laparoscopic group. Taken as a whole, the
      results slightly favor the transvaginal group. SF-12 scores were not
      statistically different at all postoperative time points except for the SF-12
      mental component which was superior in the transvaginal group at all time points
      (p < 0.05). CONCLUSION: The safety profile for transvaginal cholecystectomy
      demonstrates that this approach is safe and produces at least non-inferior
      clinical results with superior cosmesis, with a transient reduction in
      discomfort. The transvaginal approach to cholecystectomy should no longer be
      considered experimental. As a model for intersociety collaboration, the study
      demonstrated the ultimate feasibility and success of partnership as a model for
      basic research, procedural development, fundraising, and clinical trial execution
      for novel interventional concepts, regardless of physician board certification.

PMID- 29218668
TI  - Early laparoscopic adhesiolysis for small bowel obstruction: retrospective study
      of main advantages.
AB  - BACKGROUND: The problem of managing adhesional small bowel obstruction (ASBO) is
      still unsolved. A conservative medical attitude is privileged even if it is
      associated to a high rate of recurrences, while surgery is applied to cases
      showing no improvement after 48-72 h. Adhesiolysis via laparotomy has been the
      standard surgical management, but it causes other adhesions in a vicious circle.
      The aim of the study is to evaluate the advantages of early laparoscopic
      adhesiolysis as an alternative approach. METHODS: From January 2010 to April
      2017, 107 patients were admitted with a diagnosis of ASBO. Patients underwent
      medical treatment, early surgery, emergency surgery or delayed surgery after
      failure of medical treatment. A retrospective review and explorative statistical
      analysis were performed using graphical diagnostic plots, Mann-Whitney (MW) test,
      Kolmogorov-Smirnov (KS) test, exact binomial test, and chi 2 test. RESULTS:
      Medical treatment led to resolution in the 77.3% of cases, but patients exhibit
      much more recurrences than those in the surgical group (chi 2 p < .001). They
      also show a longer fasting time (MW p = .027; KS p = .102), a doubled number of
      radiological exams (MW p < .001; KS p < .001), and more major complications than
      those in the early surgery group. Early surgery group is associated to shorter
      fasting time (MW p < .001; KS p < .001), much shorter hospital stay (MW p < .001;
      KS p = .002) and a smaller number of radiological exams (MW p = .005; KS p =
      .002) compared with delayed surgery group. The laparoscopic group shows
      significantly earlier regain of intestinal transit (MW p < .001; KS p = .002),
      shorter fasting time (MW p = .002; KS p = .008), reduced number of radiological
      exams (MW p = .003; KS p = .014), reduced hospital stay (MW p < .001; KS p =
      .005), and no more complications than the open surgery group. CONCLUSIONS: Early
      laparoscopic surgery can be proposed as an effective alternative treatment for
      ASBO.

PMID- 29218669
TI  - Laparoscopy as a useful selection tool for patients with prior surgery and
      peritoneal metastases suitable for multimodality treatment strategies.
AB  - BACKGROUND: Complete macroscopic cytoreduction in patients with peritoneal
      carcinomatosis (PC) is the basic requirement for long-term survival. Diagnostic
      laparoscopy (DL) can be difficult and of limited clinical value secondary to
      postoperative or tumor-induced adhesions. The aim of this study was to evaluate
      the role of DL in patients with prior surgery and PC. METHODS: The database of
      the surgical department of the University Medical Center of Regensburg was
      reviewed (9/2010-10/2014) selecting for DL in patients with PC. The operative
      report had a standardized format allowing for the determination of the extent of
      the intra-abdominal visible area and the extent of tumor on the surface of the
      small intestine. For the classification we used our own developed score. RESULTS:
      DL was performed in 102 patients. The complete abdominal cavity was evaluable in
      48%. At least two quadrants and the largest part of the small intestine could be
      assessed in 70%. 37% of the patients had massive tumor manifestation on the small
      intestine or its mesentery. PCI (Peritoneal Cancer Index) could not be calculated
      in 71% of the patients due to incomplete visualization of the abdominal cavity
      and/or multiple tumor manifestations on the small intestine. 54% of patients were
      classified as non-resectable and 85% who seemed suitable for cytoreductive
      surgery underwent a CCR-0 resection and HIPEC. CONCLUSIONS: In spite of prior
      surgery and PC, DL is frequently possible and a useful tool to define the extent
      of tumor spread. Lots of patients can be prevented from needless open laparotomy.
      The extent of tumor involvement of the small intestine seems to be more relevant
      than calculation of the PCI to determine the potential for complete resection.
      Therefore, in the presence of adhesions, inspection of the complete abdominal
      cavity does not offer added clinical benefit and further adhesiolysis can be
      avoided.

PMID- 29218670
TI  - Systematic review of robotic low anterior resection for rectal cancer.
AB  - BACKGROUND: Potential advantages of robotic surgery, such as 3-dimensional high
      definition vision, wrist-like movements of instruments, stable camera holding,
      motion filter for tremor-free surgery, and improved ergonomics, may provide
      better clinical, oncological, and functional outcomes in rectal cancer surgery,
      as suggested in many comparative studies. However, there has not been a
      systematic review specific to LAR/TME for rectal cancer that includes both
      robotic versus laparoscopic and robotic versus open comparative studies. METHODS:
      The PubMed and Scopus databases were systematically searched in a two-step
      process, first for all robotic publications, and then within those results, for
      studies that compared perioperative, oncologic, or functional outcomes of robotic
      versus laparoscopic or open LAR/TME. Randomized controlled trials, systematic
      reviews, and independent database population studies were included in the
      analysis. RESULTS: Thirteen publications reporting on 24,526 patients met the
      inclusion criteria. Two studies compared robotic and open surgery, ten compared
      robotic and laparoscopic surgery, and one study compared all three. Robotic
      surgery resulted in increased operating times, reduced blood loss, fewer
      transfusions, shorter hospital stay, and comparable oncologic outcomes versus
      open surgery, and reduced conversion and impotency rates versus laparoscopic
      surgery. CONCLUSIONS: Robotic surgery is comparable to open and laparoscopic
      surgery concerning oncologic outcomes and seems to provide some clinical and
      functional benefits, although evidence is limited.

PMID- 29218671
TI  - Robotic versus laparoscopic right colectomy: an updated systematic review and
      meta-analysis.
AB  - BACKGROUND: In the right colon surgery, there is a growing literature comparing
      the safety of robotic right colectomy (RRC) to that of laparoscopic right
      colectomy (LRC). With this paper we aim to systematically revise and meta-analyze
      the latest comparative studies on these two minimally invasive procedures.
      METHODS: A systematic review of studies published from 2000 to 2017 in the
      PubMed, Scopus, and Embase databases was performed. Primary endpoints were
      postoperative morbidity and mortality. Secondary endpoints were blood loss,
      conversion to open surgery, harvested lymph node anastomotic leak, postoperative
      hemorrhage, abdominal abscess, postoperative ileus, time to first flatus, non
      surgical complications, wound infections, hospital stay, and incisional hernia
      and costs. A subgroup analysis was performed on those series presenting only
      extracorporeal anastomosis in both arms. RESULTS: After screening 355 articles,
      11 articles with a total of 8257 patients were eligible for inclusion. Operative
      time was found to be significantly shorter for the laparoscopic procedures in the
      pooled analysis (SMD - 0.99 95% CI - 1.4 to - 0.6, p < 0.001). Conversion to open
      surgery was more common during laparoscopic procedures than during the robotic
      ones (RR 1.7; 95% CI 1.1-2.6, p = 0.02). No significant differences in mortality
      (RR 0.47; 95% CI 0.18-1.23, p = 0.124) and postoperative complications (RR 1.05;
      95% CI 0.9-1.2, p = 0.5) were found between LRC versus RRC. The pooled mean time
      to first flatus was higher in the laparoscopic group (SMD 0.85 days; 95% CI 0.16
      1.54, p = 0.016). Hospital costs were significantly higher in RRCs (SMD - 0.52;
      95% CI - 0.52 to - 0.04, p = 0.035). CONCLUSIONS: RRC can be regarded as a
      feasible and safe technique. Its superiority in terms of postoperative recovery
      must be confirmed by further large prospective series comparing RRC and LRC
      performed with the same anastomotic technique. RRC seemed to be associated with
      higher costs than LRC.

PMID- 29218672
TI  - Effect of academic status on outcomes of surgery for rectal cancer.
AB  - BACKGROUND: The purpose of our study was to investigate surgical outcomes
      following advanced colorectal procedures at academic versus community
      institutions. METHODS: The SPARCS database was used to identify patients
      undergoing Abdominoperineal resection (APR) and Low Anterior Resection between
      2009 and 2014. Linear mixed models and generalized linear mixed models were used
      to compare outcomes. Laparoscopic versus open procedures, surgery type, volume
      status, and stoma formation between academic and community facilities were
      compared. RESULTS: Higher percentages of laparoscopic surgeries (58.68 vs.
      41.32%, p value < 0.0001), more APR surgeries (64.60 vs. 35.40%, p value <
      0.0001), more high volume hospitals (69.46 vs. 30.54%, p value < 0.0001), and
      less stoma formation (48.00 vs. 52.00%, p value < 0.0001) were associated with
      academic centers. After adjusting for confounding factors, academic facilities
      were more likely to perform APR surgeries (OR 1.35, 95% CI 1.04-1.74, p value =
      0.0235). Minorities and Medicaid patients were more likely to receive care at an
      academic facility. Stoma formation, open surgery, and APR were associated with
      longer LOS and higher rate of ED visit and 30-day readmission. CONCLUSION:
      Laparoscopy and APR are more commonly performed at academic than community
      facilities. Age, sex, race, and socioeconomic status affect the facility at which
      and the type of surgery patients receive, thereby influencing surgical outcomes.

PMID- 29218673
TI  - Results of endoscopic vacuum-assisted closure device for treatment of upper GI
      leaks.
AB  - BACKGROUND: Esophageal perforations and postoperative leakage of
      esophagogastrostomies are considered to be life-threatening conditions due to the
      potential development of mediastinitis and consecutive sepsis. Vacuum-assisted
      closure (VAC) techniques, a well-established treatment method for superficial
      infected wounds, are based on a negative pressure applied to the wound via a
      vacuum-sealed sponge. Endoluminal VAC (E-VAC) therapy as a treatment for GI
      leakages in the rectum was introduced in 2008. E-VAC therapy is a novel method,
      and experience regarding esophageal applications is limited. In this
      retrospective study, the experience of a high-volume center for upper GI surgery
      with E-VAC therapy in patients with leaks of the upper GI tract is summarized. To
      our knowledge, this series presents the largest patient cohort worldwide in a
      single-center study. METHODS: Between October 2010 and January 2017, 77 patients
      with defects in the upper gastrointestinal tract were treated using the E-VAC
      application. Six patients had a spontaneous perforation, 12 patients an
      iatrogenic injury, and 59 patients a postoperative leakage in the upper
      gastrointestinal tract. RESULTS: Complete restoration of the esophageal defect
      was achieved in 60 of 77 patients. The average duration of application was 11.0
      days, and a median of 2.75 E-VAC systems were used. For 21 of the 77 patients, E
      VAC therapy was combined with the placement of self-expanding metal stents.
      CONCLUSION: This study demonstrates that E-VAC therapy provides an additional
      treatment option for esophageal wall defects. Esophageal defects and mediastinal
      abscesses can be treated with E-VAC therapy where endoscopic stenting may not be
      possible. A prospective multi-center study has to be directed to bring evidence
      to the superiority of E-VAC therapy for patients suffering from upper GI defects.

PMID- 29218674
TI  - Correction to: Long-term outcomes of patients with early gastric cancer found to
      have lesions for which endoscopic treatment is not indicated on histopathological
      evaluation after endoscopic submucosal dissection.
AB  - In Table 1, the second item in the right-hand column "Extra-indication" should be
      changed to "Out of indication". The correct version of Table 1 is displayed.

PMID- 29218675
TI  - Thoracotomy versus video-assisted thoracoscopic surgery (VATS) in stage III
      empyema-an analysis of 217 consecutive patients.
AB  - BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a
      high morbidity and mortality. According to the American Thoracic Society, pleural
      empyema gets graduated into three stages, with surgery being indicated in
      intermediate stage II and chronic stage III. Evidence for the feasibility of a
      minimally-invasive video-assisted thoracoscopic approach in stage III empyema for
      pulmonary decortication is still little. METHODS: Retrospective single-center
      analysis of patients conducted to surgery for chronic stage III pleural empyema
      from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n =
      110) or conventional open surgery by thoracotomy (n = 107). Multiple regression
      analysis and propensity score matching was used to evaluate the influence of
      operation technique (thoracotomy versus VATS) on the length of post-operative
      hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p =
      0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post
      operative complication- (61 patients in thoracotomy- and 55 patients in VATS
      group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and
      mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ
      between both groups; the length of (post-operative) stay at intensive care unit
      was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and
      prolonged air leak rate were similar among both groups, leading to a similar
      overall and post-operative length of hospital stay in both groups. Adjusted to
      clinically and statistically relevant confounders, multiple regression analysis
      showed an influence of the surgical technique on length of post-operative stay
      after pair matching of the patients (n = 84 in each group) by propensity score (B
      = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of
      0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in
      late stage (III) pleural empyema is feasible and safe. The decrease in post
      operative hospitalization demonstrated by adjusted multiple regression analysis
      may indicate the minimally-invasive approach being safe, more tolerable for
      patients, and more effective.

PMID- 29218676
TI  - Morbidity and mortality from a propensity score-matched, prospective cohort study
      of laparoscopic versus open total gastrectomy for gastric cancer: data from a
      nationwide web-based database.
AB  - BACKGROUND: Controversy persists regarding the technical feasibility of
      laparoscopic total gastrectomy (LTG), and to our knowledge, no prospective study
      with a sample size sufficient to investigate its safety has been reported. We
      aimed to compare the postoperative morbidity and mortality rates in patients
      undergoing LTG and open total gastrectomy (OTG) for gastric cancer in
      prospectively enrolled cohort using nationwide web-based registry. METHODS: From
      August 2014 to July 2015, consecutive patients undergoing LTG or OTG (925 and
      1569 patients, respectively) at the participating institutions were enrolled
      prospectively into the National Clinical Database registration system. We
      constructed propensity score (PS) models separately in four facility yearly case
      volume groups, and evaluated the postoperative morbidity and mortality in PS
      matched 1024 patients undergoing LTG or OTG. RESULTS: The incidence of overall
      morbidity were 84 (16.4%) in the OTG and 54 (10.3%) in the LTG groups (p =
      0.01).The incidence of anastomotic leakage and pancreatic fistula grade B or
      above were not significantly different between the two groups (LTG 5.3% vs. OTG
      6.1%, p = 0.59, LTG 2.7% vs. OTG 3.7%, p = 0.38, respectively). There were also
      no significant differences in the 30-day and in-hospital mortality rates between
      the two groups (LTG 0.2% vs. OTG 0.4%, p = 0.56; LTG 0.4% vs. OTG 0.4%, p = 1.00,
      respectively). CONCLUSION: The results from our nationally representative data
      analysis showed that LTG could be a safe procedure to treat gastric cancer
      compared to OTG. The indication for LTG should be considered carefully in a
      clinical setting.

PMID- 29218677
TI  - 40 Hz Auditory Steady-State Response: The Impact of Handedness and Gender.
AB  - The 40 Hz auditory steady-state response (ASSR) is a periodic response to a
      periodic stimulation. Its sources are located in the primary auditory cortex and
      the asymmetry of the planum temporale has previously been associated with hand
      preference and gender-related differences; thus subject's handedness and gender
      could potentially influence ASSRs. Nevertheless, electrophysiological studies of
      ASSRs are mainly dominated by right-handed participants and the observed findings
      can only be generalized to the right-handed populations. However, for a potential
      use of 40 Hz ASSR as a translational biomarker of neuropsychiatric disorders, it
      is important to investigate the response in association to handedness and gender.
      We included an equal number of left-handed and right-handed males and females and
      recorded EEG responses during left-ear, right-ear and both ears stimulation. The
      results of the study suggest that the processing of 40 Hz auditory stimulation
      depends on the subjects' gender and handedness: significantly lower phase-locking
      and strength of 40 Hz ASSRs were observed in left-handed females as compared to
      left-handed males, but right-handers did not differ in 40 Hz ASSRs. Our
      observation of the opposite impact of gender in the examined handedness groups
      stresses the importance of careful consideration of handedness and gender factors
      when evaluating the determinants of inter individual variability of 40 Hz ASSRs.
      This finding is of particular importance for clinical studies in psychiatry and
      neurology.

PMID- 29218678
TI  - Low-dose CT for lung cancer screening: opportunities and challenges.
AB  - Lung cancer is among the most frequently diagnosed cancers worldwide and the
      leading cause of cancer death in both males and females. Screening for lung
      cancer coupled with earlier intervention has long been studied as an approach to
      mortality reduction. However, minimal progress was achieved until recently, when
      lowdose spiral computed tomography (LDCT) screening demonstrated a 20% reduction
      in mortality from lung cancer in a randomized controlled trial (RCT), the
      National Lung Screening Trial, from the United States. On the basis of this
      finding, LDCT has been recommended for lung cancer screening in high-risk
      populations by several clinical guidelines. However, results from the following
      independent RCTs in Europe failed to show consistent conclusions. In addition,
      intractable problems gradually emerged with the progress of LDCTscreening. This
      paper summarizes and discusses the main observations and challenges of LDCT
      screening for lung cancer. Before spreading implementation of LDCTscreening,
      challenges, including high false-positive rates, overdiagnosis, enormous costs,
      and radiation risk, must be addressed. Complementary biomarkers and technical
      improvement are expected in the field of lung cancer screening in the near
      future.

PMID- 29218679
TI  - Possibility of women treated with fertility-sparing surgery for non-epithelial
      ovarian tumors to safely and successfully become pregnant-a Chinese retrospective
      cohort study among 148 cases.
AB  - This study was performed to evaluate the oncological and reproductive outcomes of
      childbearing-age women treated with fertility-sparing surgery (FSS) for non
      epithelial ovarian tumors in China. One hundred and forty eight non-epithelial
      ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015
      from two medical centers in China were identified. Progression-free survival
      (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis
      suggested that delivery after treatment is related to PFS (P = 0.023), whereas
      histology significantly influenced OS. Cox regression analysis suggested that
      only histology was associated with PFS and OS (P < 0.05). Among the 129 women who
      completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44
      women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including
      35 live births without birth defects. Non-epithelial ovarian tumors can achieve
      fulfilling prognosis after FSS and chemotherapy. Histology might be the only
      independent prognostic factor for PFS and OS. FSS followed by ACT appeared to
      have little or no effect on fertility. Meanwhile, postoperative pregnancy did not
      increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not
      beneficial for fertility.

PMID- 29218681
TI  - Management Strategies to Facilitate Optimal Outcomes for Patients Treated with
      Delayed-release Dimethyl Fumarate.
AB  - Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has
      demonstrated significant efficacy in adults with relapsing-remitting multiple
      sclerosis. Incidences of flushing and gastrointestinal adverse events are common
      in the first month after delayed-release dimethyl fumarate initiation. Our
      objective was to propose mitigation strategies for adverse events related to
      initiation of delayed-release dimethyl fumarate in the treatment of patients with
      multiple sclerosis. Studies of individually developed mitigation strategies and
      chart reviews were evaluated. Those results, as well as mitigation protocols
      developed at multiple sclerosis care centers, are summarized. Key steps to
      optimize the effectiveness of delayed-release dimethyl fumarate treatment include
      education prior to and at the time of delayed-release dimethyl fumarate
      initiation, initiation dose protocol gradually increasing to maintenance dose,
      dietary suggestions for co-administration with food, gastrointestinal symptom
      management with over-the-counter medications, flushing symptom management with
      aspirin, and temporary dose reduction. Using the available evidence from clinical
      trials and evaluations of post-marketing studies, these strategies to manage
      gastrointestinal and flushing symptoms can be effective and helpful to the
      patient when initiating delayed-release dimethyl fumarate.

PMID- 29218680
TI  - Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three
      Randomized, Double-Blind, Placebo-Controlled Trials.
AB  - INTRODUCTION: Valbenazine is a novel vesicular monoamine transporter 2 inhibitor
      approved for the treatment of tardive dyskinesia in adults. OBJECTIVE: Using data
      from double-blind, placebo-controlled trials, analyses were conducted to evaluate
      the cardiovascular effects of once-daily valbenazine in patients with a
      psychiatric disorder who developed tardive dyskinesia after exposure to a
      dopamine-blocking medication. METHODS: Data were pooled from three 6-week, double
      blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121),
      and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of
      KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related
      treatment-emergent adverse events, vital sign measurements, and electrocardiogram
      parameters. RESULTS: The pooled safety population included 400 participants
      (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n =
      112). A history of cardiac disorders was present in 11.8% of participants, and
      74.3% were taking a concomitant medication with known potential for QT
      prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF
      (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and
      valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8
      mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, -
      2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine
      vs. placebo. No statistically significant differences were observed between
      placebo and valbenazine in cardiovascular-related, treatment-emergent adverse
      events. No notable additional effects on cardiovascular outcomes were found with
      up to 48 weeks of valbenazine treatment. CONCLUSIONS: Results from double-blind,
      placebo-controlled trials showed no apparent difference between valbenazine and
      placebo on cardiovascular outcomes. No additional cardiovascular risk was
      detected during a longer extension study with valbenazine.

PMID- 29218683
TI  - Comparison of MRI, CT, Dunn 45 degrees  and Dunn 90 degrees  alpha angle
      measurements in femoroacetabular impingement.
AB  - PURPOSE: To determine if a significant difference existed among alpha angle
      measurements between 4 imaging techniques, axial oblique CT and MRI, Dunn 45
      degrees  and Dunn 90 degrees  plain radiographs, in patients with symptomatic cam
      femoroacetabular impingement (FAI) and labral tear. METHODS: A single-surgeon
      prospective radiographic analysis of consecutive non-arthritic and non-dysplastic
      -patients with symptomatic FAI and labral tears who underwent surgery was
      performed. Alpha angle was measured using standard techniques as described by
      Notzli. Cam morphology was defined via alpha angle measurement of >50.5 degrees.
      Group comparisons were made using ANOVA and chi-squared test. Sample size
      calculation was performed prior to study enrollment. RESULTS: 31 subjects (16
      female; 33.5 +/- 10.5 years mean age) were included. There was a significant
      difference in alpha angle measurements between all 4 imaging techniques (F
      [3,120] = 8.144; p<0.001), with the Dunn 45 degrees  view (66.3 +/- 11.4 degrees
      ) significantly greater than all 3 other techniques (Dunn 90 degrees  [57.5 +/-
      10.7 degrees ; p = 0.015], MRI [53.3 +/- 11.5 degrees ; p<0.001], and CT (54.9 +/
      11.6 degrees ; p = 0.001). There was no significant difference in alpha angle
      between Dunn 90 degrees , MRI, and CT. There was a significant difference in the
      observed number of hips with cam morphology between imaging techniques (chi2 9.4;
      p = 0.025). CONCLUSIONS: The Dunn 45 degrees  radiograph yielded a significantly
      higher alpha angle than Dunn 90 degrees , axial oblique MRI, and CT imaging
      modalities. Use of the Dunn 90 degrees  or axial oblique MRI or CT as the
      threshold for cam osteoplasty may result in untreated symptomatic cam FAI. The
      authors recommend the Dunn 45 degrees  radiograph as the most sensitive
      evaluation of cam morphology.

PMID- 29218682
TI  - The RIMES Statement: A Checklist to Assess the Quality of Studies Evaluating Risk
      Minimization Programs for Medicinal Products.
AB  - INTRODUCTION: Pharmaceutical risk minimization programs involve interventions
      designed to support safe and appropriate use of medicines. Currently, information
      regarding the evaluation of these programs is not publicly reported in a
      standardized and transparent manner. To address this gap, we developed and
      piloted a quality reporting checklist entitled the Reporting recommendations
      Intended for pharmaceutical risk Minimization Evaluation Studies (RIMES).
      METHODS: Checklist development was guided by three sources: (1) a theoretical
      framework derived from program theory and process evaluation; (2) public health
      intervention design and evaluation principles; and (3) a review of existing
      quality reporting checklists. Two raters independently reviewed 10 recently
      published (2012-2016) risk minimization program evaluation studies using the
      proposed checklist. Inter-rater reliability of the checklist was assessed using
      Cohen's Kappa and Gwet's AC1. RESULTS: A 43-item checklist was generated. Results
      indicated substantial inter-rater reliability overall (kappa = 0.65, AC1 = 0.65)
      and for three (key information, design and evaluation) of the four subscales
      (kappa >= 0.64, AC1 >= 0.64). The fourth subscale (implementation) showed low
      reliability based on Cohen's Kappa, but substantial reliability based on the AC1
      (kappa = 0.17, AC1 = 0.61). CONCLUSIONS: The RIMES statement augments relevant
      elements from existing quality reporting guidelines with items that address
      aspects of intervention design, implementation and evaluation specific to
      pharmaceutical risk minimization programs. Our results show that the RIMES
      statement reliably measures key dimensions of reporting quality. This tailored
      checklist is an important first step in improving the reporting quality of risk
      minimization evaluation studies and may ultimately help to improve the quality of
      these interventions themselves.

PMID- 29218684
TI  - Feasibility of arthroscopic autologous chondrocyte implantation in the hip using
      an injectable hydrogel.
AB  - INTRODUCTION: In the long term the treatment of articular cartilage defects of
      the hip has the most direct impact on the postoperative outcome and should
      diminish degenerative changes caused by different pathologies. The purpose of
      this prospective feasibility study is to describe technical aspects of
      arthroscopic, injectable autologous chondrocyte implantation in the hip and to
      report the short-term outcome. METHODS: Full-thickness cartilage defects of 13
      patients were treated arthroscopically with an injectable autologous chondrocyte
      transplantation product (Novocart Inject, Tetec) in a 2-step surgical procedure.
      Patient-related outcome was assessed with iHOT 33, EQ-5D and Non Arthritic Hip
      Score at baseline (day before transplantation), after 6 weeks and 3, 6 and 12
      months. RESULTS: 13 out of 13 patients (all men) with a mean age of 32.7 +/- 6.9
      years and an average defect size of 1.9 +/- 1.0 cm2 were available for follow-up
      after a mean of 12 months (range 6-24 months). All defects were located on the
      acetabulum and 11 were associated with a labral lesion of 2.9 hours size.
      Femoroacetabular impingement (10 cam, 2 combined, 1 pincer) was the cause of all
      defects. An overall statistically significant improvement was observed for all
      assessment scores. CONCLUSIONS: In this study we present the feasibility and
      short-term data of an arthroscopic injectable autologous chondrocyte transplant
      as a treatment option for full-thickness cartilage defects of the hip. All
      patient-administered assessment scores demonstrated an increase in activity
      level, improvement in quality of life and reduction of pain after a 12-month
      follow-up. Further randomised controlled trails with long-term follow-up and
      additional morphological assessment are needed.

PMID- 29218685
TI  - Patient-reported quality of life and hip function after 2-stage revision of
      chronic periprosthetic hip joint infection: a cross-sectional study.
AB  - INTRODUCTION: Very limited information is available regarding patient-reported
      health-related quality of life (HRQoL) and hip function following treatment for
      chronic periprosthetic hip joint infection (PJI). Patient-reported outcome
      measures provide essential information to clinicians of the impact a treatment
      have on patient's lives. The purpose of this study was to examine patient
      reported HRQoL and hip function after a completed re-implantation in a 2-stage
      revision. METHOD: 82 patients were identified retrospectively in the National
      Patient Register. 57 patients were alive and asked to complete the questionnaires
      EuroQol-5D (EQ-5D) and Oxford Hip Score (OHS) in November 2014. Results were
      compared to normative population data for EQ-5Dindex. Patients re-infected after
      a completed 2-stage revision were compared with not re-infected. RESULTS: 45
      patients completed the questionnaires. Mean time since re-implantation was 8.2
      years (95% CI [confidence interval], 7.7-0.87). The EQ-5D index mean for the 2
      stage group was 0.71 (0.64; 0.77) whereas the general population mean is 0.85
      (0.84-0.85), p = 0.0004. The 2-stage revision patients scored significantly lower
      on every EQ-5D dimension. The re-infected group mean EQ-5D index score was
      significantly lower compared to the not re-infected group, p = 0.003. The EQ-VAS
      mean score was 58.2 (57.3-68.3) and the mean OHS for the group was 29.2 (25.4
      33.0). CONCLUSIONS: Patients who undergo 2-stage revision after a PJI have lower
      scores on HRQoL than the general population. Patients who are re-infected
      following revision have a lower HRQoL score than patients not re-infected. Future
      research should focus on optimising patient-reported outcomes after treatment for
      PJI.

PMID- 29218686
TI  - Early death following revision total hip arthroplasty.
AB  - INTRODUCTION: The frequency of primary total hip arthroplasty procedures is
      increasing, with a subsequent rise in revision procedures. This study aims to
      describe timing and surgical mortality associated with revision total hip
      arthroplasty (THA) compared to those on the waiting list. METHODS: All patients
      from a single institution who underwent revision total hip arthroplasty or were
      added to the waiting list for the same procedure between 2003 and 2013 were
      recorded. Mortality rates were calculated at 30 and 90 days following surgery or
      addition to the waiting list. RESULTS: 561 patients were available for the
      survivorship analysis in the surgical group. Following exclusion, 901 and 484
      patients were available for the 30 and the 90-day analysis in the revision THA
      waiting list group. 30- and 90-day mortality rates were significantly greater for
      the revision THA group compared to the waiting list group (excess surgical
      mortality at 30 days = 0.357%, p = 0.037; odds ratio of 5.22, excess surgical
      mortality at 90 days = 0.863%, p = 0.045). CONCLUSIONS: Revision total hip
      arthroplasty is associated with a significant excess surgical mortality rate
      until 90 days post-operation when compared to the waiting list population. We
      would encourage other authors with access to larger samples to use our method to
      quantify excess mortality after both primary and revision arthroplasty
      procedures.

PMID- 29218687
TI  - Decline in allogeneic blood transfusion usage in total hip arthroplasty patients:
      National Inpatient Sample 2009 to 2013.
AB  - INTRODUCTION: Although total hip arthroplasty (THA) is an effective treatment for
      end-stage arthritis, it is also associated with substantial blood loss that may
      require allogeneic blood transfusion. However, these transfusions may increase
      the risk of certain complications. The purpose of our study is to evaluate: (i)
      the incidence/trends of allogeneic blood transfusion; (ii) the associated risk
      factors and adverse events; and (iii) the discharge disposition, length of stay
      (LOS), and costs for these patients between 2009 and 2013. METHODS: The National
      Inpatient Sample database was used to identify 1,542,366 primary THAs performed
      between 2009 and 2013. Patients were stratified based on demographics, economic
      data, hospital characteristics, comorbidities, and whether or not allogeneic
      transfusion was received. Logistic regression was performed to evaluate the risk
      factors for transfusion and postoperative complications. RESULTS: From 2009 to
      2013, allogeneic transfusions were used in 16.9% of primary THAs, with a
      declining annual incidence. Except for obesity, all comorbidities were associated
      with increased likelihood of receiving a transfusion. Allogeneic transfusion
      patients were more likely to experience surgical site infections or pulmonary
      complications (p<0.001 for all). These patients were more likely to be discharged
      to a short-term care facility (p<0.001). Additionally, they had a greater mean
      LOS (p<0.001) and higher median hospital costs and charges when compared to their
      non-transfused counterparts. CONCLUSIONS: While the observed decline in
      allogeneic transfusion usage is encouraging, further efforts should focus on
      preoperative patient optimisation. Given the projected increase in demand for
      primary THAs, orthopaedic surgeons must be familiar with safe and effective blood
      conservation protocols.

PMID- 29218688
TI  - Is dual mobility associated with an increased risk of revision for infection?
      Matched cohort of 231 cases of dual-mobility cups and 231 fixed cups.
AB  - INTRODUCTION: We used a matched cohort of 231 cases of revision of primary dual
      mobility cups (DMC) total hip arthroplasty (THA) and 231 cases of fixed cups (FC)
      THA, to determine whether (i) revision for infection was more frequent when using
      DMC-THA than FC-THA; (ii) Causes for revision were significantly different.
      METHODS: The French Society of Orthopaedics and Traumatology carried out a
      prospective multicentre study from 2010 to 2011. The inclusion criterion was an
      exhaustive collection of 1st revision THA (at least 1 component revised, re
      revision excluded). 2,044 1st revision cases were prospectively collected; 251
      (13.5%) were revision of DMC-THA and 1,793 were revision of FC-THA (87.7%). We
      defined a matching process (1:1) between the 2 cohorts. 231 DMC-THAs were
      eligible for comparison with 231 FC-THAs. RESULTS: 47 (20.3%) FC-THAs were
      revised for infection and 54 (23.3%) DMC-THAs. There was no statistical
      difference (p = 0.43). 41 (17.7%) FC-THAs were revised for dislocation, compared
      to 11 (4.7%) DMC-THAs (p<0.001). DISCUSSION: The main finding of our study was
      that DMC was not associated with an increased risk of revision for infection
      compared to standard THA. THA revision for infection was not correlated to the
      type of cup used. It is mandatory to report on comparable types of patients when
      comparing outcomes. For similar patient profiles (i) DMC-THAs were not revised
      more often for infection than FC-THA (ii) FC-THAs were revised 4 times more for
      dislocation than DMC-THA.

PMID- 29218689
TI  - Preliminary results of a 3D-printed acetabular component in the management of
      extensive defects.
AB  - INTRODUCTION: The treatment of extensive bone loss and massive acetabular defects
      can be compounded by several challenges and pitfalls. The survivorship following
      acetabular revision with extensive bone loss is still unsatisfactory. The goal of
      the present study was to analyse the outcomes of 3D-printed patient-specific
      acetabular components in the management of extensive acetabular defects and
      combined pelvic discontinuity (PD). METHODS: 9 patients underwent revision THA
      using 3D-printed custom acetabular components to reconstruct extensive acetabular
      defects. The Paprosky classifications were determined in all patients. The
      primary outcome measure was the implant-associated failure rate. RESULTS: 1 out
      of 9 patients suffered an implant-associated complication (11%). The overall
      implant-associated survival rate was 89%. The overall complication rate was 56%.
      CONCLUSIONS: The patient-specific acetabular component technique shows promise
      for the treatment of patients with severe acetabular defects in revision THA.
      Further research aimed at reducing costs and improving the complication rate are
      warranted.

PMID- 29218690
TI  - Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation
      of pathological response with diffusion-weighted MRI and apoptotic markers.
AB  - PURPOSE: In this prospective observational study, we aimed to report the
      applicability and tolerability of neoadjuvant volumetric modulated arc therapy
      with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in
      patients with locally advanced rectal cancer (LARC), and to evaluate the
      correlation of pathological response with apparent diffusion coefficient (ADC)
      measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and
      apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or
      N+ rectal cancer who preoperatively received SIB-VMAT and concurrent
      chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers
      including the nucleosomes and cell-free DNA fragments in the serum samples were
      examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC
      measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or
      chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in
      8 patients (27%), while in 10 patients (33%) near-complete pathological response
      was obtained. Posttreatment ADC was significantly higher in patients with pCR
      compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed
      that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3%
      for distinguishing the patients with pCR from other responders. On the other
      hand, posttreatment DNA integrity values were revealed lower than the
      pretreatment values (p = 0.36). Also, the results revealed an insignificant
      increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS:
      Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible
      treatment regimen in LARC with tolerable side effects, and improved local control
      rate and pCR rate.

PMID- 29218691
TI  - Reliability and validity assessment of administrative databases in measuring the
      quality of rectal cancer management.
AB  - PURPOSE: Measurement and monitoring of the quality of care using a core set of
      quality measures are increasing in health service research. Although
      administrative databases include limited clinical data, they offer an attractive
      source for quality measurement. The purpose of this study, therefore, was to
      evaluate the completeness of different administrative data sources compared to a
      clinical survey in evaluating rectal cancer cases. METHODS: Between May 2012 and
      November 2014, a clinical survey was done on 498 Lombardy patients who had rectal
      cancer and underwent surgical resection. These collected data were compared with
      the information extracted from administrative sources including Hospital
      Discharge Dataset, drug database, daycare activity data, fee-exemption database,
      and regional screening program database. The agreement evaluation was performed
      using a set of 12 quality indicators. RESULTS: Patient complexity was a difficult
      indicator to measure for lack of clinical data. Preoperative staging was another
      suboptimal indicator due to the frequent missing administrative registration of
      tests performed. The agreement between the 2 data sources regarding
      chemoradiotherapy treatments was high. Screening detection, minimally invasive
      techniques, length of stay, and unpreventable readmissions were detected as
      reliable quality indicators. Postoperative morbidity could be a useful indicator
      but its agreement was lower, as expected. CONCLUSIONS: Healthcare administrative
      databases are large and real-time collected repositories of data useful in
      measuring quality in a healthcare system. Our investigation reveals that the
      reliability of indicators varies between them. Ideally, a combination of data
      from both sources could be used in order to improve usefulness of less reliable
      indicators.

PMID- 29218694
TI  - Training vascular access surgeons: technicians or specialists?
AB  - Internationally, vascular access (VA) surgery is delivered in a varied and
      diverse fashion and subsequently, training in vascular access is poorly defined.
      Experience of VA during surgical training has implications on future practice.
      The scope of VA procedures is increasing, yet the focus in vascular training
      remains largely in the technical aspects of surgery rather than the more
      comprehensive aspects of surgery applied to dialysis and renal care. To achieve
      special skills in vascular access surgery may require a change to traditional
      training with an additional focus on developing an extended portfolio of
      knowledge and skills. A small number of specialized courses and training
      facilities are developing to address these issues.

PMID- 29218693
TI  - Non-catalytic region of tyrosine kinase adaptor protein 2 (NCK2) pathways as
      factor promoting aggressiveness in ovarian cancer.
AB  - BACKGROUND: In this study we investigated the function of the non-catalytic
      region of tyrosine kinase adaptor protein 2 (NCK2) and its correlation with ITGB1
      and ITGB4 integrins in driving ovarian cancer (OvCa) aggressiveness. We also
      evaluated whether NCK2 may influence prognosis in OvCa patients. METHODS:
      Nanofluidic technology was used to analyze expression of NCK2 in 332 OvCa
      patients. To evaluate mRNA expression of NCK2, integrins and VEGFA in OvCa cell
      lines, qRT-PCR was performed. Stable NCK2 overexpression was obtained in OVCAR3.
      qRT-PCR and Western blot were performed to evaluate expression changes of VEGFA,
      vimentin, ITGB1, ITGB4, MMP2 and MMP9 under normoxia and hypoxia conditions.
      Coimmunoprecipitation (Co-IP) was performed in the A2780 cell line to study the
      interaction between NCK2 and proteins of interest. To investigate whether NCK2
      can influence anchorage-independent growth, a soft agar assay was completed.
      Transwell invasion assay was performed on stable-transfected OVCAR-3 cell lines.
      RESULTS: Nanofluidic data showed NCK2 can play an important role as a factor
      promoting tumor aggressiveness and survival in OvCa. This role was also linked to
      the behaviors of ITGB1 and ITGB4. Moreover, in cells overexpressing NCK2, the
      expression of vimentin, MMP2, MMP9, VEGFA and ITGB1, but not of ITGB4 was induced
      by hypoxia. Co-IP showed that NCK2 can directly bind ITGB1, but not VEGFA. NCK2
      may be involved in mediating cell-extracellular matrix interactions in OvCa cells
      by influencing tumor aggressiveness. CONCLUSIONS: This study provides evidence of
      a possible role of NCK2 as biomarker of OvCa progression.

PMID- 29218692
TI  - EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged
      over 40: Outcome in primary high-grade osteosarcoma.
AB  - INTRODUCTION: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the
      first prospective international study for patients 41-65 years old with high
      grade bone sarcoma treated with an intensive chemotherapy regimen derived from
      protocols for younger patients with high-grade skeletal osteosarcoma. METHODS:
      Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was
      suggested, but patients treated with other regimens at the investigators' choice
      were also eligible for the study. RESULTS: The present report focuses on the
      subgroup of 218 patients with primary high-grade osteosarcoma. With a median
      follow-up of 47 months, the 5-year probability of overall survival (OS) was 66%
      in patients with localized disease and 22% in case of synchronous metastases. The
      5-year OS in patients with localized disease was 29% in pelvic tumors, and 70%
      and 73% for extremity or craniofacial locations, respectively. In primary
      chemotherapy, tumor necrosis >=90% was reported in 21% of the patients. There
      were no toxic deaths; however, hematological toxicity was considerable with 32%
      of patients experiencing 1 or more episodes of neutropenic fever. The incidence
      of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%,
      respectively. After methotrexate, 23% of patients experienced delayed excretion,
      in 4 cases with nephrotoxicity. CONCLUSIONS: In patients over 40 years of age
      with primary high-grade osteosarcoma, an aggressive approach with chemotherapy
      and surgery can offer the probability of survival similar to that achieved in
      younger patients. Chemotherapy-related toxicity is significant and generally
      higher than that reported in younger cohorts of osteosarcoma patients treated
      with more intensive regimens.

PMID- 29218695
TI  - Author's reply to: Comments on a stripping method to remove stuck catheter and a
      plea to adopt a large size hemodialysis catheters.

PMID- 29218696
TI  - A modular vascular access training program for higher surgical trainees.
AB  - INTRODUCTION: Access surgery is delivered by vascular/transplant surgeons with a
      division that is defined by historic practice. This has resulted in an
      inconsistent training pattern. We aimed to design a focused, modular training
      program (The Brighton Vascular Access Fellowship) providing trainees with a
      reproducible level of exposure and competence. METHODS: The programme was 16 days
      over 8 weeks on a one-to-one basis with candidates expected to be performing
      procedures as first surgeon with ongoing, formative assessment. The outpatient
      setting took the format of a one-stop clinic to involve planning and the follow
      up. Assessment was through caseload exposure and conventional statistical
      analyses to obtain median values (as proxy measures of training exposure
      consistency). Assessment of confidence and capability was through an
      electronically distributed qualitative survey tool. RESULTS: A total of 14
      candidates completed the programme by June 2017. Operative exposure was obtained
      for 11 (79%) with a total of 471 cases of which 286 were conducted as first
      surgeon. There was a median of 32 cases by each candidate with 25 of the cases
      performed as first surgeon. Qualitative assessment revealed that 13 of 14 (93%)
      were either practicing independently or no longer required the trainer to scrub
      in for the operation. A total of 13 of 14 (93%) strongly agreed that they felt
      comfortable with offering a basic access service. CONCLUSIONS: Focused modular
      training might be one of the answers to the current era of restricted and
      sometimes inconsistent training in some aspects of surgery. This model is
      reproducible and may be applicable in other aspects of training.

PMID- 29218697
TI  - Quantitative assessment of reflux in commercially available needle-free IV
      connectors.
AB  - INTRODUCTION: Blood reflux is caused by changes in pressure within intravascular
      catheters upon connection or disconnection of a syringe or intravenous tubing
      from a needle-free connector (NFC). Changes in pressure, differing with each
      brand of NFC, may result in fluid movement and blood reflux that can contribute
      to intraluminal catheter occlusions and increase the potential for central-line
      associated bloodstream infections (CLABSI). METHODS: In this study, 14 NFC brands
      representing each of the four market-categories of NFCs were selected for
      evaluation of fluid movement occurring during connection and disconnection of a
      syringe. Study objectives were to 1) theoretically estimate amount of blood
      reflux volume in microliters (MUL) permitted by each NFC based on exact component
      measurements, and 2) experimentally measure NFC volume of fluid movement for
      disconnection reflux of negative, neutral and anti-reflux NFC and fluid movement
      for connection reflux of positive displacement NFC. RESULTS: The results
      demonstrated fluid movement/reflux volumes of 9.73 MUL to 50.34 MUL for negative
      displacement, 3.60 MUL to 10.80 MUL for neutral displacement, and 0.02 MUL to
      1.73 MUL for pressure-activated anti-reflux NFC. Separate experiment was
      performed measuring connection reflux of 18.23 MUL to 38.83 MUL for positive
      displacement NFC connectors. CONCLUSIONS: This study revealed significant
      differences in reflux volumes for fluid displacement based on NFC design. While
      more research is needed on effects of blood reflux in catheters and NFCs, results
      highlight the need to consider NFCs based on performance of individual connector
      designs, rather than manufacturer designation of positive, negative and neutral
      marketing categories for NFCs without anti-reflux mechanisms.

PMID- 29218698
TI  - Risk factors of overactive bladder syndrome and its relation to sexual function
      in menopausal women.
AB  - BACKGROUND: Overactive bladder syndrome is a common and annoying complication
      worldwide that could negatively affect the quality of life of afflicted
      individuals. We aimed to determine the prevalence and risk factors of overactive
      bladder syndrome and its relation to sexual function in healthy menopausal women.
      METHODS: This cross-sectional study was done on 340 women aged 45-60 years in
      Tabriz, northwest Iran, during 2015-2016. Data were collected using a demographic
      data questionnaire, the Overactive Bladder Syndrome Score, and the McCoy Female
      Sexuality Questionnaire. RESULTS: Fifty-six (16.5%), 63 (18.5%), and 10 (2.9%) of
      the participating women had mild, moderate, and severe overactive bladder
      syndrome, respectively. Predictors of overactive bladder included: night sweats,
      central prolapse, episiotomy, varicose disease, illiteracy or education at the
      primary level, systolic blood pressure >140 mmHg and lack of physical activity.
      We found a significant difference between the women with and without overactive
      bladder with respect to the total score and sub-domain scores related to sex
      partner (p = 0.029) and sexual interest (p = 0.049). CONCLUSIONS: The prevalence
      of overactive bladder was quite high in this study. Since sexual dysfunction is
      not an easy topic to talk about and can affect women's quality of life,
      physicians should consider talking about these issues besides urinary issues to
      all middle-aged women.

PMID- 29218699
TI  - Clinical outcome of cardioembolic stroke treated by intravenous thrombolysis.
AB  - INTRODUCTION: Cardioembolic stroke (CS) in patients without thrombolytic
      treatment is associated with a worse clinical outcome and higher mortality
      compared to other types of stroke. The aim of this study was to determine the
      clinical outcome of CS in patients treated by intravenous thrombolysis (IVT).
      MATERIAL AND METHODOLOGY: Data of patients from the SITS-EAST register (Safe
      Implementation of Treatments in Stroke) were analyzed in patients who received
      IVT treatment from 2000 to April 2014. The effect of the stroke etiology
      according to ICD-10 classification on outcome was analyzed using a univariate and
      multivariate analysis. The outcomes were assessed as follows: excellent clinical
      outcome (modified Rankin scale (mRS) 0-1) at 3 months, the rate of symptomatic
      intracranial hemorrhage (sICH), mortality, and improvement at 24 hours after IVT.
      RESULTS: Data of 13 772 patients were analyzed. CS represented 30% of all
      strokes. The mean age of patients with CS, atherothrombotic stroke, lacunar
      stroke, and other stroke was 70.8, 66.7, 66.2, and 63.3 years, respectively (P <
      .001). Severity of stroke on admission by median NIHSS score was 13 points in
      patients with CS, 12 points - in atherothrombotic stroke, 7 points - in lacunar
      stroke, and 10 points-in other stroke types (P < .001). No difference in
      mortality was detected among atherothrombotic and CS; however, atherothrombotic
      strokes had higher odds of sICH [OR = 1.63 (95% CI: 1.07-2.47), P = .023], lower
      odds of early improvement [OR = 0.79 (95% CI: 0.72-0.86), P < .001], and
      excellent clinical outcome [OR = 0.77 (95% CI: 0.67-0.87), P < .001] compared
      with CS. CONCLUSIONS: Cardioembolic strokes are not associated with increased
      mortality. Patients with CS are less likely to have sICH and have better outcome
      after IVT.

PMID- 29218700
TI  - Non-persistence in ischaemic stroke: Risk of recurrent vascular events.
AB  - OBJECTIVES: Ischaemic stroke is one of the leading causes of death and disability
      worldwide. Although the secondary preventive medication should be continued for
      life, its use commonly declines in time. This may lead to recurrent vascular
      events. In this study, we investigated if during a long follow-up period
      discontinuation of medication (non-persistence) in real life ischaemic stroke
      patients increased the risk of recurrent vascular events. MATERIALS AND METHODS:
      This was a retrospective cohort study with the data retrieved from a database and
      the original patient records. The occurrence of new vascular events was
      determined from the electronic medical record. Medication use at time of follow
      up was ascertained using the pharmacy-link in the electronic medical file and
      through a telephone interview. Primary endpoint was recurrent vascular events.
      Patients with two or more vascular risk factors were considered as having a high
      risk profile. RESULTS: A total of 286 patients (persistent n = 182 and non
      persistent n = 104) were included. After median follow-up period of 51/2 years in
      the persistent group 14.8% had a recurrent vascular event, vs 23.1% in the non
      persistent group (P = .801). In the patients with a high-risk profile, the
      persistent group had significantly less recurrent vascular events than the non
      persistent group (23.5% against 46.4% P = .021). CONCLUSION: After a long follow
      up period, ischaemic stroke patients with a high vascular risk profile who
      stopped taking their secondary preventive medication had an increased risk of a
      recurrent vascular events.

PMID- 29218701
TI  - A longitudinal cohort study on the impact of the clobazam shortage on patients
      with epilepsy.
AB  - OBJECTIVE: Drug shortages are occurring at an increasing rate. From May to
      October 2016, there was a shortage of a level I critical antiepileptic drug,
      clobazam. We aimed to study the impact of this shortage on patients with
      epilepsy. METHODS: Adult patients from Calgary's Comprehensive Epilepsy Program
      who were taking clobazam were approached to participate in the study. Baseline
      data from the clinic prospective registry included clinical variables and
      presurvey patient-reported outcomes (PROs) such as the Global Assessment of
      Severity of Epilepsy, the Global Assessment of Disability Associated with
      Seizures, and the Quality of Life in Epilepsy questionnaire. We used a mixed
      methods cross-sectional questionnaire via telephone. We analyzed quantitative
      data using descriptive methods and qualitative data using a phenomenological
      approach. RESULTS: Of the 85 eligible patients, 84% (n = 71) agreed to
      participate. Participants ranged from 18 to 78 years old, and 59.2% of
      participants were female. Overall, 80% of participants experienced some form of
      medication change due to the shortage. No significant differences were found in
      the pre- and during-shortage PRO data. However, 6 important themes emerged
      regarding the impact of the antiepileptic drug shortage on patients: (1)
      communication and awareness, (2) burden on patients and caregivers, (3) physical
      impact, (4) psychological impact, (5) health care provider assistance in
      navigating the shortage, and (6) policy change. SIGNIFICANCE: We examined the
      impact of the clobazam shortage on patients with epilepsy from the patient's
      perspective and identified 6 important themes. As a result, we were able to gain
      insight into what patients need to cope with drug shortages and make
      recommendations that can help mitigate the impact of shortages on patients in the
      future. Further research is needed to better understand drug shortages from the
      patient's perspective in various settings and conditions.

PMID- 29218702
TI  - Deep brain stimulation for drug-resistant epilepsy.
AB  - OBJECTIVES: To review clinical evidence on the antiepileptic effects of deep
      brain stimulation (DBS) for drug-resistant epilepsy, its safety, and the factors
      influencing individual outcomes. METHODS: A comprehensive search of the medical
      literature (PubMed, Medline) was conducted to identify relevant articles
      investigating DBS therapy for drug-resistant epilepsy. Reference lists of these
      articles were used to source further articles. RESULTS: Stimulation of the
      anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to
      decrease the frequency of refractory seizures. Half of all patients from clinical
      studies experienced a 46%-90% seizure reduction with ANT-DBS, and a 48%-95%
      seizure reduction with HC-DBS. The efficacy of stimulating other targets remains
      inconclusive due to lack of evidence. Approximately three-fourths of patients
      receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are
      responders-experiencing a seizure reduction of at least 50%. The time course of
      clinical benefit varies dramatically, with both an initial lesional effect and
      ongoing stimulation effect at play. Improved quality of life and changes to
      cognition or mood may also occur. Side effects are similar in nature to those
      reported from DBS therapy for movement disorders. Several factors are potentially
      associated with stimulation efficacy, including an absence of structural
      abnormality on imaging for ANT and HC stimulation, and electrode position
      relative to the target. Certain seizure types or syndromes may respond more
      favorably to specific targets, including ANT stimulation for deep temporal or
      limbic seizures, and CMT stimulation for generalized seizures and Lennox-Gastaut
      syndrome. SIGNIFICANCE: We have identified several patient, disease, and
      stimulation factors that potentially predict seizure outcome following DBS. More
      large-scale clinical trials are needed to explore different stimulation
      parameters, reevaluate the indications for DBS, and identify robust predictors of
      patient response.

PMID- 29218703
TI  - Epidemic of large babies highlighted by use of INTERGROWTH21st international
      standard.
AB  - OBJECTIVE: To compare birth weights in central Sydney to the INTERGROWTH21st
      international standard to describe current trends in relation to optimal growth
      and to define areas that may benefit from improved obstetric surveillance and
      intervention. METHODS: Retrospective analysis of prospectively collected cohort.
      DESIGN: hospital-based cohort study. SETTING: Sydney Local Health District,
      Australia. POPULATION OR SAMPLE: women with singleton pregnancies who had first
      trimester screening for aneuploidy between 16 April, 2010 and 9 March, 2012.
      Analysis of 2966 births. MAIN OUTCOME MEASURES: Large for gestational age (LGA)
      >4000 g, >4500 g, >5000 g, >90th, >95th, >97th centiles and small for gestational
      age (SGA) <1500 g, <2500 g, <third, <fifth, <10th centiles. RESULTS: The
      proportion of infants classified as LGA was significantly higher than expected by
      the international standard, with relative risks (RRs) of 1.66 (1.44-1.88), 1.81
      (1.50-2.21) and 2.07 (1.61-2.65) for the 90th, 95th and 97th centiles,
      respectively (P < 0.0001). The number of infants classified as SGA was
      significantly lower with RRs of 0.32 (0.21-0.49), 0.38 (0.28-0.52) and 0.45 (0.37
      0.55) for the 3rd, 5th and 10th centiles, respectively (P < 0.0001). Maternal
      body mass index (BMI) and height were significantly associated with LGA infants
      as were parity and pre-existing diabetes. CONCLUSION: Comparing the international
      INTERGROWTH21st standards to our population has revealed a markedly high
      prevalence of LGA infants. The most important modifiable risk factors identified
      in early pregnancy were maternal BMI and pre-existing diabetes.

PMID- 29218704
TI  - Sacral neuromodulation for pelvic pain and pelvic organ dysfunction: A case
      series.
AB  - BACKGROUND: The use of neuromodulation is growing and it is an established
      therapy for conditions such as bladder dysfunction. It is an increasingly used
      therapy for the management of chronic perineal pain but little research is
      currently available looking at its efficacy. AIM: We present a series of 52
      patients who underwent placement of a neuromodulator, the majority of whom
      suffered from perineal pain, with most placements via the sacral hiatus. METHOD:
      Patients were asked to complete a survey recalling their symptoms prior to
      implantation and describing their symptoms and experience after. The majority had
      two leads placed via the sacral hiatus. RESULTS: Fifty-two patients had
      implantation of a permanent neuromodulator and 44 completed at least part of the
      survey. Forty-eight had leads placed via the sacral hiatus, 29 of whom had these
      leads only. Forty patients had perineal pain as an indicator and 32 reported that
      their pain improved; this difference was statistically significant (95% CI: 2.60
      4.27, P < 0.001). Bladder, bowel and sexual dysfunction were reported by about
      half the cohort with smaller numbers of improvement for each. Thirty-five
      patients reported improved quality of life and 32 said they would have the
      procedure done again. Ten patients had the device removed. CONCLUSION: We present
      the largest published case series looking at the use of sacral neuromodulation as
      a treatment option for pelvic pain and the overall results of our audit are
      promising for the ongoing use and further development of this modality as a
      management option.

PMID- 29218705
TI  - Randomized controlled study comparing the efficacy of rapid and slow withdrawal
      of antiepileptic drugs during long-term video-EEG monitoring.
AB  - OBJECTIVE: Antiepileptic drugs (AEDs) are routinely withdrawn during long-term
      video-electroencephalography (EEG) monitoring (LTM), to record sufficient number
      of seizures. The efficacy of rapid and slow AED taper has never been compared in
      a randomized control trial (RCT), which was the objective of this study. METHODS:
      In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy
      (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome
      assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to
      50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary
      outcome was difference in mean duration of LTM between the rapid and slow AED
      taper groups. Secondary outcomes included diagnostic yield, secondary generalized
      tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status
      epilepticus, and need for midazolam rescue treatment. The study was registered
      with Clinical Trial Registry-India (CTRI/2016/08/007207). RESULTS: One hundred
      forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n =
      70), between June 13, 2016 and February 20, 2017. The difference in mean LTM
      duration between the rapid and slow taper groups was -1.8 days (95% confidence
      interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time
      to first seizure (2.9 +/- 1.7 and 4.6 +/- 3.0 days in the rapid and slow taper
      groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9%
      and 2.9% in the rapid and slow taper groups, respectively, P = .04) were
      statistically significant. None of the other safety variables were different
      between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow
      taper groups respectively (P = .46). SIGNIFICANCE: Rapid AED tapering has the
      advantage of significantly reducing LTM duration over slow tapering, without any
      serious adverse events.

PMID- 29218706
TI  - Genome-wide RNA-Seq identifies Fas/FasL-mediated tumoricidal activity of
      embryonic stem cells.
AB  - The discovery of tumor tropism of stem cells revealed the intimate relationship
      between stem cells and tumor cells, but the functional role of stem cells in
      tumorigenesis is poorly understood. To investigate embryonic stem cell (ESC) and
      tumor cell interactions, we co-cultured mouse ESCs with mouse melanoma B16-F10
      cells or mouse pancreatic tumor Pan02 cells, and found that ESCs significantly
      inhibited tumor cell proliferation. Coculture of ESCs and tumor cells resulted in
      significant inhibition of tumorigenesis in vivo. Histological analyses indicated
      that ESCs encircled apoptotic tumor cells. We carried out time course RNA-Seq
      analyses of ESC and tumor cell co-cultures, and identified Fas/FasL signaling as
      a major pathway involved in ESC-mediated apoptosis of tumor cells. We further
      generated FADD-deficient tumor cells by CRISPR/Cas9-mediated gene editing, and
      demonstrated that FADD-deficient tumor cells were obviously resistant to ESC
      mediated inhibition of tumor cell proliferation. Our results indicate the
      Fas/FasL signaling pathway plays a critical role in ESCs-mediated tumoricidal
      activity.

PMID- 29218707
TI  - Food Effect on Rosuvastatin Disposition and Low-Density Lipoprotein Cholesterol.
AB  - Rosuvastatin is commonly prescribed for the treatment of hypercholesterolemia and
      hepatic transporter-mediated accumulation in the liver enhances its efficacy.
      Current guidelines indicate no preference for fed or fasted rosuvastatin
      administration. We investigated the association between food intake and
      rosuvastatin disposition in healthy subjects and low-density lipoprotein
      cholesterol (LDL-C)-lowering effects among patients taking rosuvastatin. We
      demonstrate that administration with food resulted in a near 40% reduction of
      rosuvastatin exposure in healthy Asian (n = 12) and Caucasian (n = 11) subjects.
      Higher rosuvastatin concentrations in Asian subjects also correlated with higher
      allele frequency of ABCG2 c.421C>A. In mice, a greater rosuvastatin liver:plasma
      ratio was noted when administered with food. Among rosuvastatin patients (n =
      156), there was no difference in dose needed to reach target LDL-C, measured LDL
      C, or lathosterol concentrations, when administered in a fed or fasting state.
      Therefore, taking rosuvastatin with food could reduce systemic concentrations,
      and subsequent myopathy risk, without compromising LDL-C-lowering benefit.

PMID- 29218708
TI  - Three-dimensional reconstruction of the cranial and anterior spinal nerves in
      early tadpoles of Xenopus laevis (Pipidae, Anura).
AB  - Xenopus laevis is one of the most widely used model organism in neurobiology. It
      is therefore surprising, that no detailed and complete description of the cranial
      nerves exists for this species. Using classical histological sectioning in
      combination with fluorescent whole mount antibody staining and micro-computed
      tomography we prepared a detailed innervation map and a freely-rotatable three
      dimensional (3D) model of the cranial nerves and anterior-most spinal nerves of
      early X. laevis tadpoles. Our results confirm earlier descriptions of the pre
      otic cranial nerves and present the first detailed description of the post-otic
      cranial nerves. Tracing the innervation, we found two previously undescribed head
      muscles (the processo-articularis and diaphragmatico-branchialis muscles) in X.
      laevis. Data on the cranial nerve morphology of tadpoles are scarce, and only one
      other species (Discoglossus pictus) has been described in great detail. A
      comparison of Xenopus and Discoglossus reveals a relatively conserved pattern of
      the post-otic and a more variable morphology of the pre-otic cranial nerves.
      Furthermore, the innervation map and the 3D models presented here can serve as an
      easily accessible basis to identify alterations of the innervation produced by
      experimental studies such as genetic gain- and loss of function experiments.

PMID- 29218709
TI  - Predicting plant immunity gene expression by identifying the decoding mechanism
      of calcium signatures.
AB  - Calcium plays a key role in determining the specificity of a vast array of
      signalling pathways in plants. Cellular calcium elevations with different
      characteristics (calcium signatures) carry information on the identity of the
      primary stimulus, ensuring appropriate downstream responses. However, the
      mechanism for decoding calcium signatures is unknown. To determine this, decoding
      of the salicylic acid (SA)-mediated plant immunity signalling network controlling
      gene expression was examined. A dynamic mathematical model of the SA-mediated
      plant immunity network was developed. This model was used to predict responses to
      different calcium signatures; these were validated empirically using quantitative
      real-time PCR to measure gene expression. The mechanism for decoding calcium
      signatures to control expression of plant immunity genes enhanced disease
      susceptibility 1 (EDS1) and isochorismate synthase 1 (ICS1) was identified.
      Calcium, calmodulin, calmodulin-binding transcription activators (CAMTA)3 and
      calmodulin binding protein 60g (CBP60g) together amplify each calcium signature
      into three active signals, simultaneously regulating expression. The time
      required for calcium to return to steady-state level also quantitatively
      regulates gene expression. Decoding of calcium signatures occurs via nonlinear
      interactions between these active signals, producing a unique response in each
      case. Key properties of the calcium signatures are not intuitive, exemplifying
      the importance of mathematical modelling approaches. This approach can be applied
      to identifying the decoding mechanisms of other plant calcium signalling
      pathways.

PMID- 29218710
TI  - Turning local knowledge and experience into innovative tools for quality care
      during labor and childbirth: The BOLD project experience.

PMID- 29218711
TI  - Defining quality of care during childbirth from the perspectives of Nigerian and
      Ugandan women: A qualitative study.
AB  - OBJECTIVE: To explore what "quality of care" means to childbearing women in
      Nigeria and Uganda, as a means of ensuring that women's voices and opinions are
      prioritized when developing interventions to improve quality in maternity care
      provision. METHODS: Qualitative methods, with a purposive sample of women in
      Nigeria and Uganda. Participants were asked to define quality of care and to
      provide examples of when it was and was not provided. Thematic analysis was used
      to synthesize findings based on an a priori framework (the WHO quality of care
      framework). RESULTS: 132 in-depth interviews and 21 focus group discussions are
      included. Participants spontaneously discussed each of the WHO framework domains
      of quality of care. Data were richest across the domains of effective
      communication, respect and dignity, emotional support, competent and motivated
      human resources, and essential physical resources. Women believed that good
      quality of care ensured optimal psychological and physiological outcomes for the
      woman and her baby. Positive interpersonal relationships between women and health
      providers were important. These included supportive care, building rapport, and
      using positive and clear language. CONCLUSION: To provide good quality of care,
      maternity services should consider and act on the expectations and experiences of
      women and their families.

PMID- 29218712
TI  - Disposable skin staplers for closure of linear gastrointestinal incisions in
      dogs.
AB  - OBJECTIVE: To report the clinical features and outcomes of linear
      gastrointestinal incisions closed with skin staples in dogs. STUDY DESIGN:
      Historical cohort study. ANIMALS: 333 client-owned dogs. METHODS: Medical records
      from 1 private referral hospital were searched for dogs that underwent
      gastrointestinal surgery between November 1999 and October 2015. Cases were
      included if skin staplers were used to close linear gastrointestinal incisions.
      Information regarding preoperative, surgical, and postoperative factors was
      collected. RESULTS: Complications were diagnosed in 8 of 245 (3.27%) dogs,
      including 3 of 245 (1.22%) dogs that died or were euthanized, 3 of 245 (1.22%)
      dogs with incisional dehiscence, and 2 of 245 (0.81%) dogs with attachment of a
      linear foreign body to the staples at the intestinal lumen. Dehiscence was noted
      at the enterotomy sites in 3 dogs at a mean time of 44 hours after surgery (SD +/
      6.93). Two dogs presented with another linear foreign body that was attached to
      the staples in the intestinal lumen at postoperative days 24 and 42. The risk
      factors associated with incisional dehiscence included multiple gastrointestinal
      incisions performed in 1 surgery (chi2 , P < .001) and the presence of a linear
      foreign body (chi2 , P = .02253). No associations were detected between dogs'
      age, sex, weight, surgery time, indication for surgical intervention, surgery
      location in the gastrointestinal tract, or surgeon experience and incisional
      dehiscence. CONCLUSION: Skin staplers provide safe and effective closure of
      gastrotomies, enterotomies, and colonotomies in dogs. This method is reliable,
      efficient, and affordable in the hands of veterinary surgeons with varying skill
      levels.

PMID- 29218713
TI  - Low levels of genetic structuring in King George whiting Sillaginodes punctatus
      across two geographic regions.
AB  - Postlarvae of King George whiting Sillaginodes punctatus, a commercially
      important fish species in southern Australia, were collected from multiple
      locations across south and south-eastern Australia. Genetic analyses using seven
      microsatellite markers found little evidence of genetic structure suggesting high
      levels of connectivity between the regions. The results found no evidence of a
      distinct source spawning population within the south-eastern range sampled in
      this study.

PMID- 29218714
TI  - Using a service design model to develop the "Passport to Safer Birth" in Nigeria
      and Uganda.
AB  - OBJECTIVE: To demonstrate how a human-centered service design approach can
      generate practical tools for good-quality childbirth care in low-resource
      settings. METHODS: As part of the WHO "Better Outcomes in Labour Difficulty"
      (BOLD) project, a service design approach was used in eight Ugandan and Nigerian
      health facilities and communities to develop the "Passport to Safer Birth." There
      are three phases: Research for Design, Concept Design, and Detail Design. These
      generated design principles, design archetype personas, and Passport prototypes.
      Data collection methods included desk research, interviews, group discussions,
      and journey mapping to identify touchpoints where the woman interacts with the
      health system. RESULTS: A total of 90 interviews, 12 observation hours, and 15
      group discussions were undertaken. The resulting design principles were: a shared
      and deeper understanding of pregnancy and childbirth among family and community;
      family readiness for decision-making and action; and the woman's sense of being
      in control and being cared for. Four archetype personas of women emerged:
      Vulnerable; Passive; Empowered; Accepter. Subsequent development of the Passport
      to Safer Birth tools addressed three domains: Care Mediator; Expectation Manager;
      and Pregnancy Assistant. CONCLUSION: The service design approach can create
      innovative, human-centered service solutions to improve maternity care
      experiences and outcomes in low-resource settings.

PMID- 29218715
TI  - Therapists' and Clients' Perceptions of Bonding as Predictors of Outcome in
      Multisystemic Therapy(r).
AB  - This longitudinal study examined whether strength of and balance in self-reported
      caregiver, youth, and therapist emotional bonds in mid- and late treatment
      predicted outcomes in Multisystemic Therapy of adolescent behavior problems in a
      sample of 164 caregiver-youth dyads. Strength of and balance in bonds related to
      outcome in different ways, depending on the source of the report and time.
      Results showed a limited association between family members' emotional connection
      with the therapist and treatment outcome, whereas therapists' perceptions of bond
      with the caregiver showed highly significant associations across time. Caregiver
      therapist agreement on emotional connection at both time points predicted
      therapist evaluation of treatment success and successful termination, but this
      was largely explained by therapists' level of alliance. Balance in bonds with the
      therapist between caregiver and youth had no significant associations with any
      outcome. The study major limitations such as examining only one component of
      alliance and possible implications are discussed.

PMID- 29218716
TI  - Pregnancy in a patient with Netherton syndrome.

PMID- 29218717
TI  - Genetic composition of a population of natural common bream Abramis brama * roach
      Rutilus rutilus hybrids and their morphological characteristics in comparison
      with parent species.
AB  - Common bream Abramis brama, roach Rutilus rutilus and their hybrids were
      collected in the Dobczyce Reservoir in southern Poland in 2006-2013 to study
      whether it is better for a hybrid individual to resemble and compete with one of
      its parents, or to minimize competition by having a distinctive phenotype. All
      hybrids were F1 crosses and originated predominantly (93.2%) from matings between
      female A. brama and male R. rutilus parents. In morphometric analyses, a newly
      defined coefficient, L3  = 2.5 (body mass) (LS  * body depth)-1 , which enables
      forms with similar length-depth proportions but different length-mass
      relationships to be distinguished was used. Morphometric and meristic
      characteristics of the hybrids were intermediate in comparison with the parental
      species, with small but significant deviation towards R. rutilus in longitudinal
      body dimensions (trunk and tail length) and towards A. brama in body cross
      sectional shape (body depth and L3 coefficient). This may result in a more R.
      rutilus like propulsion in hybrids and a more A. brama like ability to manoeuvre.

PMID- 29218718
TI  - Comparing apples to oranges: A commentary on the Mayo study of MYD88 significance
      in Waldenstrom's macroglobulinemia.

PMID- 29218719
TI  - The communication and emotional support needs to improve women's experience of
      childbirth care in health facilities in Southwest Nigeria: A qualitative study.
AB  - OBJECTIVE: To improve women's childbirth experiences in health facilities, their
      psychosocial and communication needs have to be met. However, what constitutes
      these specific needs is poorly understood, particularly in Sub-Saharan Africa.
      This paper explores women's needs for communication and emotional support during
      facility-based childbirth. METHODS: Qualitative research was conducted in a large
      referral maternity hospital and its catchment communities in Akure, Nigeria. In
      depth interviews (IDIs) and focus group discussions (FGDs) were conducted among
      women of reproductive age, midwives, doctors, and facility administrators.
      Thematic analysis was used to synthesize findings, and then interpreted within
      the context of this study and existing quality of care framework. RESULTS: Forty
      two IDIs and 10 FGDs are included in this analysis. Participants reported such
      needs as communication in simple words in local language by healthcare staff,
      having their husbands as birth companions, spiritual support, and prayers from
      family members and healthcare providers. CONCLUSION: To increase, improve, and
      sustain facility-based childbirth in Nigeria, health systems should appreciate
      the uniqueness and importance of each woman's needs during childbirth. Practical
      and sustainable actions should be taken to meet these needs, within the confines
      of the acceptable sociocultural norms.

PMID- 29218720
TI  - Long-term risk of cervical cancer following conization of cervical
      intraepithelial neoplasia grade 3-A Danish nationwide cohort study.
AB  - Using nationwide Danish registries we examined the long-term risk of cervical
      cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3)
      (including adenocarcinoma in situ (AIS)) on the cone compared to women with a
      normal cytology test. Initially, we identified women born 1918-1990, who were
      recorded as living in Denmark between January 1, 1978 and December 31, 2012. From
      the Pathology Data Bank information on CIN3 on the cone, margins status,
      histological type of CIN3 and cervical cytology results was extracted. Cox
      proportional hazard model was used to estimate the relative risk of subsequent
      cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508
      women with a normal cytology test. Overall, women diagnosed with CIN3 had a
      higher risk of subsequent cervical cancer compared to women with normal cytology
      (HR = 2.06; 95%CI: 1.81-2.35). Analyses according to time since conization showed
      elevated risks in all time periods, and 25 years or more after conization the
      relative risk was significantly increased (HR = 2.56; 95%CI: 1.37-4.77). Twenty
      years or more after conization, also women with negative margins had an increased
      relative risk (HR = 2.49; 95%CI: 1.12-5.57). In addition, the long-term relative
      risk of cervical cancer varied with the different histological types of CIN3 and
      was highest for AIS (HR = 7.50; 95%CI: 1.87-30.01, 10-14 years after conization).
      In conclusion, women diagnosed with CIN3 on the cone have a long-lasting
      increased risk of cervical cancer even when the margins on the cone are negative.

PMID- 29218721
TI  - Functional characterization of a second pedal peptide/orcokinin-type neuropeptide
      signaling system in the starfish Asterias rubens.
AB  - Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a
      family of neuropeptides that have been identified in several phyla. Recently,
      starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in
      the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of
      transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK
      type precursors: an SMP-type precursor (A. rubens PP-like neuropeptide precursor
      1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed
      analysis of ArPPLNP1 expression in A. rubens and here we report the first
      functional characterization ArPPLNP2-derived neuropeptides. Sequencing of a cDNA
      encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides
      (ArPPLN2a-k), the structures of several of which were confirmed using mass
      spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived
      from this precursor using mRNA in situ hybridization and immunohistochemistry
      revealed a widespread distribution, including expression in radial nerve cords,
      circumoral nerve ring, digestive system, tube feet and innervation of
      interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2-derived
      neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body
      wall-associated apical muscle, contrasting with the relaxing effect of ArPPLN1b
      (ArSMP) on these preparations. ArPPLN2h does, however, cause dose-dependent
      relaxation of cardiac stomach preparations, with greater potency/efficacy than
      ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In
      conclusion, there are similarities in the expression patterns of ArPPLNP1 and
      ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides
      derived from these two PP/OK-type precursors in starfish.

PMID- 29218722
TI  - Coupling of microRNA-directed phased small interfering RNA generation from long
      noncoding genes with alternative splicing and alternative polyadenylation in
      small RNA-mediated gene silencing.
AB  - MicroRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs) play vital
      regulatory roles in plant growth and development. Little is known about these
      small RNAs in litchi (Litchi chinensis), an economically important fruit crop
      widely cultivated in Southeast Asia. We profiled the litchi small RNA population
      with various deep-sequencing techniques and in-depth bioinformatic analyses. The
      genome-wide identification of miRNAs, their target genes, and phasiRNA-generating
      (PHAS) genes/loci showed that the function of miR482/2118 has expanded, relative
      to its canonical function. We also discovered that, for 29 PHAS loci, miRNA
      mediated phasiRNA production was coupled with alternative splicing (AS) and
      alternative polyadenylation (APA). Most of these loci encoded long noncoding
      RNAs. An miR482/2118 targeted locus gave rise to four main transcript isoforms
      through AS/APA, and diverse phasiRNAs generated from these isoforms appeared to
      target long terminal repeat (LTR) retrotransposons and other unrelated genes.
      This coupling enables phasiRNA production from different exons of noncoding PHAS
      genes and yields diverse phasiRNA populations, both broadening and altering the
      range of downstream phasiRNA-regulated genes. Our results reveal the diversity of
      miRNA and phasiRNA in litchi, and demonstrate AS/APA as a new layer of regulation
      in small RNA-mediated gene silencing.

PMID- 29218723
TI  - How Do Our Values Inform Ethical Research? A Narrative of Recognizing Colonizing
      Practices.
AB  - How do you reconcile tensions between ethical research practice, personal values,
      and disciplinary values? This article focuses on an ethical challenge involving
      the engagement of rural Indigenous community members that emerged during my PhD
      fieldwork. The narrative illustrates the necessity to engage in critical
      reflexive research practice, a process which saw me respond to my own feelings of
      "wrong" and "right," contemplate a distinction between procedural ethics and
      virtue ethics in community-based research, explore colonizing research practices,
      and endeavor to reconcile an instance where the values of community psychology
      appeared in contest. The "voice" in this narrative is that of the first author;
      the dual authorship reflects the ongoing collaboration between both authors. When
      this ethical issue came about, our relationship was one of "student" and
      "supervisor"; we are now colleagues and friends.

PMID- 29218724
TI  - Genetic disruption of fractalkine signaling leads to enhanced loss of cochlear
      afferents following ototoxic or acoustic injury.
AB  - Cochlear hair cells are vulnerable to a variety of insults like acoustic trauma
      and ototoxic drugs. Such injury can also lead to degeneration of spiral ganglion
      neurons (SGNs), but this occurs over a period of months to years. Neuronal
      survival is necessary for the proper function of cochlear prosthetics, therefore,
      it is of great interest to understand the mechanisms that regulate neuronal
      survival in deaf ears. We have recently demonstrated that selective hair cell
      ablation is sufficient to attract leukocytes into the spiral ganglion, and that
      fractalkine signaling plays a role in macrophage recruitment and in the survival
      of auditory neurons. Fractalkine (CX3 CL1), a chemokine that regulates adhesion
      and migration of leukocytes is expressed by SGNs and signals to leukocytes via
      its receptor CX3 CR1. The present study has extended the previous findings to
      more clinically relevant conditions of sensorineural hearing loss by examining
      the role of fractalkine signaling after aminoglycoside ototoxicity or acoustic
      trauma. Both aminoglycoside treatment and acoustic overstimulation led to the
      loss of hair cells as well as prolonged increase in the numbers of cochlear
      leukocytes. Lack of CX3 CR1 did not affect macrophage recruitment after injury,
      but resulted in increased loss of SGNs and enhanced expression of the
      inflammatory cytokine interleukin-1beta, when compared to mice with intact CX3
      CR1. These data indicate that the dysregulation of macrophage response caused by
      the absence of CX3 CR1 may contribute to inflammation-mediated neuronal loss in
      the deafened ear, suggesting a key role for inflammation in the long-term
      survival of target-deprived afferent neurons.

PMID- 29218727
TI  - GABAA and GABAB receptor subunit localization on neurochemically identified
      neurons of the human subthalamic nucleus.
AB  - The subthalamic nucleus (STN) is a critical excitatory signaling center within
      the basal ganglia circuitry. The activity of subthalamic neurons is tightly
      controlled by upstream inhibitory signaling centers in the basal ganglia. In this
      study, we used immunohistochemical techniques to firstly, visualize and quantify
      the STN neurochemical organization based on neuronal markers including
      parvalbumin (PV), calretinin (CR), SMI-32, and GAD65/67 . Secondly, we
      characterized the detailed regional, cellular and subcellular expression of GABAA
      (alpha1 , alpha2 , alpha3 , beta2/3 , and gamma2 ) and GABAB (R1 and R2) receptor
      subunits within the normal human STN. Overall, we found seven neurochemically
      distinct populations of principal neurons in the human STN. The three main
      populations detected were: (a) triple-labeled PV+ /CR+ /SMI32+ ; (b) double
      labeled PV+ /CR+ ; and (c) single-labeled CR+ neurons. Subthalamic principal
      neurons were found to express GABAA receptor subunits alpha1 , alpha3 , beta2/3 ,
      gamma2 , and GABAB receptor subunits R1 and R2. However, no expression of GABAA
      receptor alpha2 subunit was detected. We also found a trend of increasing
      regional staining intensity for all positive GABAA receptor subunits from the
      dorsolateral pole to ventromedial extremities. The GAD+ interneurons showed
      relatively low expression of GABAA receptor subunits. These results provide the
      morphological basis of GABAergic transmission within the normal human subthalamic
      nucleus and evidence of GABA innervation through both GABAA and GABAB receptors
      on subthalamic principal neurons.

PMID- 29218726
TI  - Healthcare providers' perspectives on labor monitoring in Nigeria and Uganda: A
      qualitative study on challenges and opportunities.
AB  - OBJECTIVE: To explore current practices, challenges, and opportunities in
      relation to monitoring labor progression, from the perspectives of healthcare
      professionals in low-resource settings. METHODS: Thematic analysis of qualitative
      data (in-depth interviews [IDIs] and focus group discussions [FDGs]) obtained
      from a purposive sample of healthcare providers and managers in selected health
      facilities in Nigeria and Uganda. RESULTS: A total of 70 IDIs and 16 FGDs with
      doctors, midwives, and administrators are included in this analysis. Labor
      monitoring encompasses a broad scope of care jointly provided by doctors and
      midwives. A range of contextual limitations was identified as barriers to
      monitoring labor progression, including staff shortages, lack of team
      cooperation, delays in responding to abnormal labor observations, suboptimal
      provider-patient dynamics, and limitations in partograph use. Perceived
      opportunities to improve current practices included streamlining clinical team
      cooperation, facilitating provider-client communication, encouraging women's
      uptake of offered care, bridging the gaps in the continuum of monitoring tasks
      between cadres, and improving skills in assessment of labor progress, and
      accuracy in its documentation. CONCLUSION: Healthcare providers face many
      challenges to effective monitoring of labor progress in low-resource settings.
      This analysis presents potential opportunities to improve labor monitoring
      practices and tools in these contexts.

PMID- 29218725
TI  - Characterization of retinal ganglion cell, horizontal cell, and amacrine cell
      types expressing the neurotrophic receptor tyrosine kinase Ret.
AB  - We report the retinal expression pattern of Ret, a receptor tyrosine kinase for
      the glial derived neurotrophic factor (GDNF) family ligands (GFLs), during
      development and in the adult mouse. Ret is initially expressed in retinal
      ganglion cells (RGCs), followed by horizontal cells (HCs) and amacrine cells
      (ACs), beginning with the early stages of postmitotic development. Ret expression
      persists in all three classes of neurons in the adult. Using RNA sequencing,
      immunostaining and random sparse recombination, we show that Ret is expressed in
      at least three distinct types of ACs, and ten types of RGCs. Using intersectional
      genetics, we describe the dendritic arbor morphologies of RGC types expressing
      Ret in combination with each of the three members of the POU4f/Brn3 family of
      transcription factors. Ret expression overlaps with Brn3a in 4 RGC types, with
      Brn3b in 5 RGC types, and with Brn3c in one RGC type, respectively. Ret+ RGCs
      project to the lateral geniculate nucleus (LGN), pretectal area (PTA) and
      superior colliculus (SC), and avoid the suprachiasmatic nucleus and accessory
      optic system. Brn3a+ Ret+ and Brn3c+ Ret+ RGCs project preferentially to
      contralateral retinorecipient areas, while Brn3b+ Ret+ RGCs shows minor
      ipsilateral projections to the olivary pretectal nucleus and the LGN. Our
      findings establish intersectional genetic approaches for the anatomic and
      developmental characterization of individual Ret+ RGC types. In addition, they
      provide necessary information for addressing the potential interplay between GDNF
      neurotrophic signaling and transcriptional regulation in RGC type specification.

PMID- 29218728
TI  - A service concept and tools to improve maternal and newborn health in Nigeria and
      Uganda.
AB  - OBJECTIVE: The "Better Outcomes in Labor Difficulty" (BOLD) project used a
      service design process to design a set of tools to improve quality of care during
      childbirth by strengthening linkages between communities and health facilities in
      Nigeria and Uganda. This paper describes the Passport to Safer Birth concept and
      the tools developed as a result. METHODS: Service design methods were used to
      identify facilitators and barriers to quality care, and to develop human-centered
      solutions. The service design process had three phases: Research for Design,
      Concept Design, and Detail Design, undertaken in eight hospitals and catchment
      communities. RESULTS: The service concept "Better Beginnings" comprises three
      tools. The "Pregnancy Purse" provides educational information to women throughout
      pregnancy. The "Birth Board" is a visual communication tool that presents the
      labor and childbirth process. The "Family Pass" is a set of wearable passes for
      the woman and her supporter to facilitate communication of care preferences.
      CONCLUSION: The Better Beginnings service concept and tools form the basis for
      the promotion of access to information and knowledge acquisition, and could
      improve communication between the healthcare provider, the woman, and her family
      during childbirth.

PMID- 29218729
TI  - Structural and molecular heterogeneity of calretinin-expressing interneurons in
      the rodent and primate striatum.
AB  - Calretinin-expressing (CR+) interneurons are the most common type of striatal
      interneuron in primates. However, because CR+ interneurons are relatively scarce
      in rodent striatum, little is known about their molecular and other properties,
      and they are typically excluded from models of striatal circuitry. Moreover, CR+
      interneurons are often treated in models as a single homogenous population,
      despite previous descriptions of their heterogeneous structures and spatial
      distributions in rodents and primates. Here, we demonstrate that, in rodents, the
      combinatorial expression of secretagogin (Scgn), specificity protein 8 (SP8)
      and/or LIM homeobox protein 7 (Lhx7) separates striatal CR+ interneurons into
      three structurally and topographically distinct cell populations. The
      CR+/Scgn+/SP8+/Lhx7- interneurons are small-sized (typically 7-11 um in somatic
      diameter), possess tortuous, partially spiny dendrites, and are rostrally biased
      in their positioning within striatum. The CR+/Scgn-/SP8-/Lhx7- interneurons are
      medium-sized (typically 12-15 um), have bipolar dendrites, and are homogenously
      distributed throughout striatum. The CR+/Scgn-/SP8-/Lhx7+ interneurons are
      relatively large-sized (typically 12-20 um), and have thick, infrequently
      branching dendrites. Furthermore, we provide the first in vivo
      electrophysiological recordings of identified CR+ interneurons, all of which were
      the CR+/Scgn-/SP8-/Lhx7- cell type. In the primate striatum, Scgn co-expression
      also identified a topographically distinct CR+ interneuron population with a
      rostral bias similar to that seen in both rats and mice. Taken together, these
      results suggest that striatal CR+ interneurons comprise at least three
      molecularly, structurally, and topographically distinct cell populations in
      rodents. These properties are partially conserved in primates, in which the
      relative abundance of CR+ interneurons suggests that they play a critical role in
      striatal microcircuits.

PMID- 29218731
TI  - Editor-in-Chief thanks the Associate Editors, Editorial Board and Referees.

PMID- 29218730
TI  - Monte Carlo study of ionization chamber magnetic field correction factors as a
      function of angle and beam quality.
AB  - PURPOSE: To use EGSnrc Monte Carlo simulations for magnetic field dosimetry to
      determine optimal measurement orientations, calculate beam quality conversion
      factors for 32 cylindrical and three parallel-plate (PP) ion chambers, evaluate
      the beam quality and angular dependence of these factors, and examine the
      magnetic field effects on %dd(10)x and TPR1020. METHODS: Beam quality conversion
      factors, kQmag, and magnetic field conversion factors, kB  = kQmag/kQ , are
      calculated as a function of chamber rotation for six cylindrical ionization
      chamber in either a 60 Co beam with a 0.35 T magnetic field or a 7 MV beam with a
      1.5 T field, both magnetic fields are perpendicular to the photon beam. The
      chambers' sensitive air volumes are varied by either using the entire geometric
      volume or excluding the air volume associated with the first 1 mm away from the
      stem. The kB and kQmag factors are evaluated using four clinical photon spectra.
      The variation in %dd(10)x and TPR1020 as a function of magnetic field for six
      photon spectra are studied using DOSXYZnrc. RESULTS: When the magnetic field is
      perpendicular to the photon beam, orienting the chamber parallel with the
      magnetic field reduces the magnetic field effect on chamber response (i.e., dose
      to air per water dose) and variations due to the unknown sensitive volume are
      essentially eliminated. Calculated kB factors are within 1% of unity for the
      majority of cylindrical chambers, although larger kB values are associated with
      chambers with high-Z electrodes. PP chambers have kB corrections as large as 8.9%
      and have a larger angular sensitivity compared to cylindrical chambers. Values of
      kB for cylindrical ion chambers are independent of beam quality, except for
      chambers with high-Z electrodes. For %dd(10)x values between 63.3% and 73.8%, kB
      varies by at most (0.26 +/- 0.15)% when the magnetic field is perpendicular to
      the photon beam and parallel to the chamber. Differences in %dd(10)x , between no
      magnetic field and with a 1.5 T field perpendicular to the photon beam are (0.04
      +/- 0.10)%, (1.89 +/- 0.10)%, and (6.20 +/- 0.10)% for a 60 Co, 7, and 25 MV
      photon beam, respectively, while TPR1020 shows less than (0.36 +/- 0.10)% change.
      Applying the ICRU-90 recommendations for stopping powers instead of ICRU-37 is
      found to change kQ (and hence kB ) by less than 0.1%. CONCLUSIONS: Orienting the
      chamber parallel to the magnetic field when the field is perpendicular to the
      photon beam will minimize the effect of the magnetic field on chamber response,
      and eliminate the problem of the unknown sensitive volume. Values of kB and kQmag
      can bring ion chamber dosimetry in magnetic fields in-line with the TG-51
      protocol. PP chamber are sensitive to the magnetic field and variation in chamber
      response due to small angular changes makes them unlikely candidates for clinical
      reference dosimetry in magnetic fields. The stability in TPR1020, as a function
      of magnetic fields and beam qualities, makes it the best beam quality specifier
      in magnetic fields.

PMID- 29218732
TI  - Single-center implementation of endoscopic submucosal dissection (ESD) in the
      colorectum: Low recurrence rate after intention-to-treat ESD.
AB  - BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) shows
      higher R0 resection and lower local recurrence rates than endoscopic mucosal
      resection (EMR) in Japan. In Europe, independent learning of ESD in the
      colorectum is feasible, but yet to be analyzed for curative resection and
      recurrence rates. METHODS: After experimental training under supervision by
      Japanese experts (T.O., N.Y.), three endoscopists independently carried out 83
      ESD procedures intention-to-treat for lesions in the entire colorectum of 67
      patients in a prospective registry (November 2009 to June 2016). RESULTS: ESD was
      feasible in 80 (96%) colorectal neoplasias (mean diameter 33.6 [+/- 1.8] mm), and
      three more required conversion to piecemeal EMR. The lesions were adenomas in 66%
      with low-grade intraepithelial neoplasia (LGIN), 29% with high-grade
      intraepithelial neoplasia, and 5% with carcinomas (G2, pT1). ESD had to be
      facilitated by the final use of snaring (hybrid-ESD, n = 45), especially in the
      initial learning period. En-bloc resection rate was 85%. Complications were
      microperforations (7%, conducive to one hemicolectomy), and delayed bleeding (1%)
      without mortality or long-term morbidity. Residual adenomas with LGIN (5%) after
      hybrid-ESD did not recur after endoscopic ablation. All malignant neoplasias
      (34%) were curatively resected without recurrence after a mean follow up of 19.5
      (+/- 3.2) months. CONCLUSIONS: During independent ESD learning in the colorectum,
      ESD intention-to-treat showed a low recurrence rate after appropriate training,
      and hybrid-ESD showed acceptable complication and recurrence rates, justifying
      hybrid-ESD as a strategy for self-completion and rescue.

PMID- 29218733
TI  - A gene-driven recovery mechanism: Drosophila larvae increase feeding activity for
      post-stress weight recovery.
AB  - Recovery from weight loss after stress is important for all organisms, although
      the recovery mechanisms are not fully understood. We are working to clarify these
      mechanisms. Here, we recorded enhanced feeding activity of Drosophila
      melanogaster larvae from 2 to 4 h after heat stress at 35 degrees C for 1 h.
      During the post-stress period, expression levels of sweet taste gustatory
      receptor genes (Grs), Gr5a, Gr43a, Gr64a, and Gr64f, were elevated, whereas
      bitter taste Grs, Gr66a, and Gr33a, were decreased in expression and expression
      of a non-typical taste receptor Gr, Gr68a, was unchanged. Similar upregulation of
      Gr5a and downregulation of Gr66a was recorded after cold stress at 4 degrees C.
      Expression levels of tropomyosin and ATP synthase beta subunit were significantly
      increased in larval mouth parts around 3 to 5 h after the heat stress. We infer
      that up-regulation of post-stress larval feeding activity, and weight recovery,
      is mediated by increasing capacity for mouth part muscular movements and changes
      in taste sensing physiology. We propose that Drosophila larvae, and likely
      insects generally, express an efficient mechanism to recover from weight loss
      during post-stress periods.

PMID- 29218735
TI  - Soft tissue re-growth after osseous resective surgery with and without fibre
      retention technique. Four-year follow-up of a randomized clinical trial.
AB  - AIM: The aim of this study was to compare the clinical outcomes and soft tissue
      rebound following Fibre Retention Osseous Resective Surgery (FibReORS) and
      Osseous Resective Surgery (ORS) over a 48-month period. MATERIALS AND METHODS:
      Thirteen chronic periodontitis patients, displaying two contra-lateral posterior
      sextants with residual intrabony defects <=3 mm in single-rooted or multi-rooted
      teeth with no or grade I furcation involvement, were treated in a split-mouth
      study model. ORS procedure was randomly applied on one side, while FibReORS on
      the contra-lateral side. Clinical measurements were recorded at 12 and 48 months
      after surgery. RESULTS: All 13 patients were available for the 48-month recall.
      At this time point, probing depth (PD) and keratinized tissue changes did not
      significantly differ between treatments. FibReORS-treated sites exhibited less
      gingival recession than ORS-treated sextants (2.1 +/- 0.3 versus 2.5 +/- 0.4 mm,
      p = .001), but comparable coronal soft tissue rebound. The mean difference of 0.4
      +/- 0.3 mm was consistent with higher amount of bone resection in the ORS group
      (0.92 +/- 0.11 versus 0.38 +/- 0.09 mm, p < .001). CONCLUSION: FibReORS resulted
      in similar PD changes and soft tissue rebound compared with ORS in posterior
      teeth with no or limited furcation involvement.

PMID- 29218734
TI  - Prognostic value of multicenter flow cytometry harmonized assessment of minimal
      residual disease in acute myeloblastic leukemia.
AB  - The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia
      is of growing interest as a prognostic marker of patients' outcome.
      Multiparameter flow cytometry (MFC), tracking leukemia-associated
      immunophenotypic patterns, has been shown in several studies to be a useful tool
      to investigate MRD. Here, we report a multicenter prospective study which allowed
      to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to
      predict outcome. This study included 276 patients, in 10 different MFC centers,
      of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and
      CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color
      tubes allowed to define each patient's multiparameter immunophenotypic
      characteristics at diagnosis, according to a Boolean combination of gates. The
      same individual diagnosis gating strategy was then applied at each MRD time point
      for each patient. MRD levels were stratified according to log by log thresholds,
      from 5 * 10-2 (the classical morphological threshold to define remission) down to
      <5 * 10-5 . MRD was found to be constantly negative (<5 * 10-5 ) for 148
      patients. Survival analyses significantly associated MRD negativity with a good
      prognosis and any positive value with poorer outcome. All P values were <0.0001
      both for disease-free and overall survival at the earliest time point (post
      induction, MRD1) as well as when considering all time points together. Finally,
      MRD levels were independent of cytogenetics and allowed in fact to further
      stratify all cytogenetics risk groups. In summary, this multicenter study
      demonstrates that a simple combination of immunophenotypic markers successfully
      allows for the detection of MRD in acute myeloblastic leukemia patients, with a
      strong correlation to outcome.

PMID- 29218736
TI  - A High-Performing Direct Carbon Fuel Cell with a 3D Architectured Anode Operated
      Below 600  degrees C.
AB  - Direct carbon fuel cells (DCFCs) are highly efficient power generators fueled by
      abundant and cheap solid carbons. However, the limited triple-phase boundaries
      (TPBs) in the fuel electrode, due to the lack of direct contact among carbon,
      electrode, and electrolyte, inhibit the performance and result in poor fuel
      utilization. To address the challenges of low carbon oxidation activity and low
      carbon utilization, a highly efficient, 3D solid-state architected anode is
      developed to enhance the performance of DCFCs below 600  degrees C. The cell with
      the 3D textile anode framework, Gd:CeO2 -Li/Na2 CO3 composite electrolyte, and
      Sm0.5 Sr0.5 CoO3 cathode demonstrates excellent performance with maximum power
      densities of 143, 196, and 325 mW cm-2 at 500, 550, and 600  degrees C,
      respectively. At 500  degrees C, the cells can be operated steadily with a rated
      power density of ~0.13 W cm-2 at a constant current density of 0.15 A cm-2 with a
      carbon utilization over 85.5%. These results, for the first time, demonstrate the
      feasibility of directly electrochemical oxidation of solid carbon at 500-600 
      degrees C, representing a promising strategy in developing high-performing fuel
      cells and other electrochemical systems via the integration of 3D architected
      electrodes.

PMID- 29218737
TI  - Unsaturated cryptophanes: Toward dual PHIP/hyperpolarised xenon sensors.
AB  - Cryptophanes, cage-molecules constituted of aromatic bowls, are now well
      recognised as powerful xenon hosts in 129 Xe NMR-based biosensing. In the quest
      of a dual probe that can be addressed only by NMR, we have studied three
      cryptophanes bearing a tether with an unsaturated bond. The idea behind this is
      to build probes that can be detected both via hyperpolarised 129 Xe NMR and para
      hydrogen induced polarisation 1 H NMR. Only two of the three cryptophanes
      experience a sufficiently fast hydrogenation enabling the para-hydrogen induced
      polarisation effect. Although the in-out xenon exchange properties are maintained
      after hydrogenation, the chemical shift of xenon encaged in these two
      cryptophanes is not strikingly modified, which impedes safe discrimination of the
      native and hydrogenated states via 129 Xe NMR. However, a thorough examination of
      the hyperpolarised 1 H spectra reveals some interesting features for the
      catalytic process and gives us clues for the design of doubly smart 1 H/129 Xe
      NMR-based biosensors.

PMID- 29218738
TI  - A recurrent mutation in the KRT17 gene responsible for severe steatocystoma
      multiplex in a large Chinese family.

PMID- 29218739
TI  - Successful liver transplantation for homozygous protein C deficiency with a type
      II mutation using a heterozygous living related donor.

PMID- 29218740
TI  - Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials
      Submitted to the US Food and Drug Administration.
AB  - Clinical trial enrichment involves prospectively incorporating trial design
      elements that increase the probability of detecting a treatment effect. The use
      of enrichment strategies in pediatric drug development has not been
      systematically assessed. We analyzed the use of enrichment strategies in
      pediatric trials submitted to the US Food and Drug Administration from 2012-2016.
      In all, 112 efficacy studies associated with 76 drug development programs were
      assessed and their overall success rates were 78% and 75%, respectively. Eighty
      eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3%
      employed multiple enrichment strategies. The highest trial success rates were
      achieved when all three enrichment strategies (practical, predictive, and
      prognostic) were used together within a single trial (87.5%), while the lowest
      success rate was observed when no enrichment strategy was used (65.4%). The use
      of enrichment strategies in pediatric trials was found to be associated with
      trial and program success in our analysis.

PMID- 29218741
TI  - A test of the substitution-habitat hypothesis in amphibians.
AB  - Most examples that support the substitution-habitat hypothesis (human-made
      habitats act as substitutes of original habitat) deal with birds and mammals. We
      tested this hypothesis in 14 amphibians by using percentage occupancy as a proxy
      of habitat quality (i.e., higher occupancy percentages indicate higher quality).
      We classified water body types as original habitat (no or little human influence)
      depending on anatomical, behavioral, or physiological adaptations of each
      amphibian species. Ten species had relatively high probabilities (0.16-0.28) of
      occurrence in original habitat, moderate probability of occurrence in
      substitution habitats (0.11-0.14), and low probability of occurrence in refuge
      habitats (0.05-0.08). Thus, the substitution-habitat hypothesis only partially
      applies to amphibians because the low occupancy of refuges could be due to the
      negligible human persecution of this group (indicating good conservation status).
      However, low occupancy of refuges could also be due to low tolerance of refuge
      conditions, which could have led to selective extinction or colonization problems
      due to poor dispersal capabilities. That original habitats had the highest
      probabilities of occupancy suggests amphibians have a good conservation status in
      the region. They also appeared highly adaptable to anthropogenic substitution
      habitats.

PMID- 29218742
TI  - Prevalence of foot disorders in captive Sardinian partridges (Alectoris barbara
      barbara Bonnaterre, 1790) as useful indicators of fitness to natural environment.
AB  - Foot health represents an issue in wild avifauna breeding practices. In
      particular, prevalence of digital ulceration (DU) and foot pad dermatitis (FPD)
      are valid indicators of welfare in wildlife conservation centres and may be
      interpreted as to fitness for bird's reintroduction into the wild. This study
      meant to test the effects of raising practices on foot pad health in captive
      Sardinian partridges (Alectoris barbara barbara Bonnaterre, 1790) reared for
      biodiversity conservation, to assess welfare and fitness to reintroduction into
      nature. A total of 22 couples were allotted into two experimental groups. In one
      group, 10 couples were housed in 10 cages for breeding partridges, consisting of
      two animals each, with metal wire flooring system, above trays where droppings
      were collected. The remaining 12 couples were housed in six aviaries, consisting
      of four animals each, on natural (earth and stones) ground. In both groups,
      partridges were fed identical diets. No significant differences of food pad
      scoring were found between birds housed in cages (2.3 +/- 0.4) and those reared
      in aviaries on natural ground (2.5 +/- 0.6). Moreover, scores of male foot pads
      for both groups (2.4 +/- 0.6) had no significant differences in comparison with
      female foot pads, independently on housing (2.5 +/- 0.4). Body mass (BM) was
      higher (+4.36%) than average BM reported for wild Sardinian partridges. Digital
      ulceration was found in the 20% of females, exclusively from the cage group. Body
      mass of females in cages with metal wire flooring appeared to be significantly (p
      < .001) and negatively correlated (r = -.528) with DU prevalence. These results
      suggest that housing conditions impacts differently on behaviour of females and
      males in one same couple, and this relates to foot health, in particular as to DU
      prevalence.

PMID- 29218743
TI  - Repeatability of pleural adenosine deaminase measurements in diagnostic
      evaluation of pleural effusions.
AB  - BACKGROUND: A follow-up thoracentesis is proposed in suspected atypical
      tuberculosis cases. The study aimed to define the variability of pleural ADA
      values across repeated thoracenteses in different types of pleural effusions
      (PEs) and to evaluate whether ADA variance, in regard to the cutoff value of 40
      U/L, affected final diagnosis. METHODS: A total of 131 patients with PEs of
      various etiologies underwent three repeated thoracenteses. ADA values were
      subsequently estimated. RESULTS: 82% and 55% of patients had greater than 10% and
      20% deviation from the highest ADA value, respectively. From those patients who
      had a variance of 20%, 36% had only increasing ADA values, while 19% had only
      decreasing values. Considering the cutoff value of 40 U/L, only in two cases, ADA
      decreased below this threshold, which concerned a man with tuberculous pleurisy
      and a woman with lymphoma both in the course of treatment. Furthermore, only in
      two cases with rising values, ADA finally exceeded the cutoff limit, which
      concerned a man with rheumatoid pleurisy and a man with tuberculous pleurisy.
      Surprisingly, malignant PEs (MPEs) showed a higher percentage of increasing
      values compared to all other exudates that did not, however, exceed the
      threshold. CONCLUSION: The determination of pleural ADA levels is a reproducible
      method for rapid tuberculosis diagnosis. The detected measurement deviations do
      not appear to affect final diagnosis. In specific situations, repeated ADA
      measurements may be valuable in directing further diagnostic evaluation. More
      investigation is needed to elucidate the possible prognostic significance of the
      increasing trend in ADA values in MPEs.

PMID- 29218744
TI  - Hybrid Silicon-Based Organic/Inorganic Block Copolymers with Sol-Gel Active
      Moieties: Synthetic Advances, Self-Assembly and Applications in Biomedicine and
      Materials Science.
AB  - Hybrid silicon-based organic/inorganic (multi)block copolymers are promising
      polymeric precursors to create robust nano-objects and nanomaterials due to their
      sol-gel active moieties via self-assembly in solution or in bulk. Such nano
      objects and nanomaterials have great potential in biomedicine as nanocarriers or
      scaffolds for bone regeneration as well as in materials science as Pickering
      emulsifiers, photonic crystals or coatings/films with antibiofouling,
      antibacterial or water- and oil-repellent properties. Thus, this Review outlines
      recent synthetic efforts in the preparation of these hybrid inorganic/organic
      block copolymers, gives an overview of their self-assembled structures and
      finally presents recent examples of their use in the biomedical field and
      material science.

PMID- 29218745
TI  - Expression of the potassium-chloride co-transporter, KCC2, within the avian song
      system.
AB  - Songbirds learn to produce vocalizations early in life by listening to, then
      copying the songs of conspecific males. The anterior forebrain pathway,
      homologous to a basal ganglia-forebrain circuit, is essential for song learning.
      The projection between the striato-pallidal structure, Area X, and the medial
      portion of the dorsolateral thalamic nucleus (DLM) is strongly hyperpolarizing in
      adults, due to a very negative chloride reversal potential (Person & Perkel,
      Neuron 46:129-140, 2005). The chloride reversal potential is determined, in part,
      by the expression level of a neuron-specific potassium-chloride cotransporter,
      KCC2, which is developmentally upregulated in mammals. To determine whether a
      similar upregulation in KCC2 expression occurs at the Area X to DLM synapse
      during development, we examined the expression level of KCC2 in adult zebra
      finches across the song system as well as during development in the Area X - DLM
      synapse. We demonstrate that KCC2 is expressed in a subset of neurons throughout
      the song system, including HVC (used as a proper name), robust nucleus of the
      arcopallium (RA), lateral magnocellular nucleus of the anterior nidopallium
      (LMAN), Area X, and DLM. The majority of pallidal-like projection neurons in Area
      X showed KCC2 immunoreactivity. In adults, KCC2 expression was robust within DLM,
      and was upregulated between 14 and 24 days post hatching, before the onset of
      song learning. Light and electron microscopic analysis indicated that KCC2
      immunoreactivity is strongly associated with the plasma membrane. Thus, in the
      song system as in the mammalian brain, KCC2 expression is well placed to modulate
      the GABAA reversal potential.

PMID- 29218746
TI  - BODIPY-Based Antiaromatic Macrocycles: Facile Synthesis by Knoevenagel
      Condensation and Unusual Aggregation-Enhanced Two-Photon Absorption Properties.
AB  - Two stable boron dipyrromethene (BODIPY)-based antiaromatic macrocycles, Mc-Fur
      and Mc-Th, were synthesized through a one-pot Knoevenagel condensation reaction
      between a BODIPY precursor and furan-2,5-dicarboxaldehyde or thiophene-2,5
      dicarboxaldehyde, respectively. 1 H NMR spectroscopic characterization of the two
      macrocycles supported their highly antiaromatic character. The oxidation
      properties of the two macrocycles were studied through electron spin resonance
      spectroscopy and UV/Vis absorption spectrophotometry, which suggested the
      formation of a stable monoradical cation species on first oxidation followed by
      an aromatic dicationic species on subsequent oxidation. Both molecules have a
      nearly planar pi-conjugated backbone and show a strong tendency to aggregate in
      solution due to efficient stacking of the antiaromatic macrocycles. Transient
      absorption and two-photon absorption (TPA) measurements in solution and
      aggregated states of the macrocycles revealed that aggregation resulted in large
      enhancement of TPA cross sections and increased excited-state lifetimes, in
      accordance with the decrease in the antiaromatic character in the aggregated
      state.

PMID- 29218747
TI  - Patient characteristics and outcome measurement in a low secure forensic
      hospital.
AB  - BACKGROUND: Health services are increasingly required to measure outcomes after
      treatment, which can be reported to the funding body and may be scrutinised by
      the public. Extensive high-quality measurements are time consuming. Routinely
      collected clinical data might, if anonymised, provide good enough evidence of
      useful change consequent on service received. RESEARCH QUESTION: Do the Health of
      the Nation Scale and the 20-item Historical, Clinical, Risk structured
      professional judgement tool scores provide evidence of clinical and risk change
      among low security hospital patients at 6 and 12 months after admission? METHODS:
      One hundred and eight men were either resident on the unit on 1 January 2011 or
      new admissions to the census date of 31 May 2013. Their routinely collected data
      were added to an outcome register following each patient's Care Programme
      Approach clinical review meeting and analysed using repeated measures t-tests
      with Bonferroni corrections. RESULTS: Most of the men, mean age 34.3 years, were
      single (93%), White British (71%) and with a primary diagnosis of schizophrenia
      (62%). There were significant reductions in the 11-item Health of the Nation
      Scale (excluding the community living condition scale) scores between baseline
      and 6 months and between 6 and 12 months, but no change on its additional 7-item
      secure subscale. Individual effect sizes indicated that 39% of the men had better
      social function, although 18% had deteriorated at 6 months. There was little
      overall change in the 20-item Historical, Clinical, Risk; individual effect sizes
      indicated that 11 men (15%) were rated as being at lower risk level and 10 (14%)
      at higher after 6 months in the study. CONCLUSIONS/IMPLICATIONS FOR CLINICAL
      PRACTICE: Standard clinical measures are promising as indicators of change in low
      security hospital patients. Risk ratings may be conservative, but at this stage
      of a secure hospital admission, higher scores may be as likely to indicate
      progress in identifying and quantifying risks as apparent increase in risk.
      Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29218748
TI  - Adolescent non-drinkers: Who are they? Social relations, school performance,
      lifestyle factors and health behaviours.
AB  - INTRODUCTION AND AIMS: Traditionally, non-drinking adults or young adults have
      been associated with health deficits rather than health benefits. However, as the
      proportion of Swedish non-drinking adolescents has doubled since 2000, their
      health profiles are of interest. The aim of the present study is to examine
      whether social relations, school characteristics, lifestyle factors or health
      behaviours distinguish adolescent non-drinkers from adolescent drinkers, and if
      their health profiles have changed from 2004 to 2012. DESIGN AND METHODS: Data
      from the Survey of Adolescent Life in Vestmanland, a health survey biennially
      distributed to all 9th graders (15-16 years) in a medium-sized Swedish county,
      was used. In total, 2872 students in 2004 and 2045 students in 2012 were
      included. RESULTS: Non-drinkers were distinguished from drinkers in both 2004 and
      2012 by elevated parental supervision, a lower rate of school truancy and lower
      rates of cannabis use, use of other illicit drugs, daily smoking and lower scores
      on antisocial behaviour, but more problems of getting new friends. No differences
      between 2004 and 2012 were found. DISCUSSION AND CONCLUSIONS: Non-drinkers
      presented more adaptive and healthier behaviours than their drinking peers, but
      it is difficult to determine whether their health benefits were related to their
      improved alcohol status or to the more general trend towards adaptation that
      occurred from 2004 to 2012 among adolescents.

PMID- 29218750
TI  - Pelvic lymphangioleiomyomatosis diagnosed by FNA of cyst fluid.

PMID- 29218749
TI  - Evidence for miRNA-mediated modulation of the host transcriptome in cnidarian
      dinoflagellate symbiosis.
AB  - Reef-building corals and other cnidarians living in symbiotic relationships with
      intracellular, photosynthetic dinoflagellates in the genus Symbiodinium undergo
      transcriptomic changes during infection with the algae and maintenance of the
      endosymbiont population. However, the precise regulatory mechanisms modulating
      the host transcriptome are unknown. Here, we report apparent post-transcriptional
      gene regulation by miRNAs in the sea anemone Aiptasia, a model system for
      cnidarian-dinoflagellate endosymbiosis. Aiptasia encodes mainly species-specific
      miRNAs, and there appears to have been recent differentiation within the Aiptasia
      genome of miRNAs that are commonly conserved among anthozoan cnidarians. Analysis
      of miRNA expression showed that both conserved and species-specific miRNAs are
      differentially expressed in response to endosymbiont infection. Using cross
      linking immunoprecipitation of Argonaute, the central protein of the miRNA
      induced silencing complex, we identified miRNA binding sites on a transcriptome
      wide scale and found that the targets of the miRNAs regulated in response to
      symbiosis include genes previously implicated in biological processes related to
      Symbiodinium infection. Our study shows that cnidarian miRNAs recognize their
      mRNA targets via high-complementarity target binding and suggests that miRNA
      mediated modulations of genes and pathways are important during the onset and
      maintenance of cnidarian-dinoflagellate endosymbiosis.

PMID- 29218751
TI  - Comparing levels of blood alcohol concentration and indicators of impairment in
      nightlife patrons.
AB  - INTRODUCTION AND AIMS: Breathalyser estimate of blood alcohol concentration (BAC)
      is widely used as an objective intoxication measure, but is not always practical
      in nightlife contexts. This study uses in situ data collected in nightlife
      environments to explore how four measures of intoxication are related so as to
      inform the development of a more practical and reliable method of differentiating
      intoxication for people working in the night-time economy. DESIGN AND METHODS:
      Nightlife patron interviews were conducted in five Australian cities.
      Participants completed demographic questions and were asked about current session
      (past 12 h) alcohol use, and four different measures of intoxication were
      assessed: BAC, participant's self-reported intoxication (0-10), interviewer
      rating of the participant's intoxication (0-10) and interviewer-rated number of
      the participants' of physical signs of intoxication. RESULTS: A total of 7028
      patrons were surveyed and n = 5273 included in analysis. Mean age was 23.9 years
      (SD = 6.36); 61.5% were male. There was a significant difference in occurrence of
      all observable intoxication symptoms across differing levels of BAC (P < 0.001).
      All visible symptoms became more common as intoxication increased, except for
      talking very quickly/talkative and giggly symptoms. As BAC levels increase, the
      extent of the disagreement between self-rated and interviewer-rated intoxication
      measures widens. Exhibiting four or more visible intoxication symptoms emerged as
      a reliable method for observers to identify intoxicated patrons. DISCUSSION AND
      CONCLUSIONS: As BAC increases, people become worse at estimating their own
      intoxication, but sober observers remain relatively accurate. Findings provide
      support for efforts to strengthen and enforce responsible service of alcohol.

PMID- 29218752
TI  - Addressing the needs of first-time fathers in Tasmania: A qualitative study of
      father-only antenatal groups.
AB  - OBJECTIVE: To examine how first-time fathers in rural Tasmania experienced father
      only antenatal support/education groups. DESIGN: Semistructured interviews with
      expectant fathers were used for this study. Purposive sampling was used to
      recruit fathers in 2014. Participants were recruited face-to-face via email
      through a government health service and not-for-profit organisation that runs a
      state-wide fatherhood program. Several participants were recruited through a
      company that holds antenatal education classes for men in a pub. Data were
      analysed thematically. SETTING: Three rural Tasmanian areas (South, Central Coast
      and Northern Midlands) PARTICIPANTS: Twenty-five men from three rural areas of
      Tasmania, >=18 years, about to become first-time father with partner at least 20
      weeks pregnant. MAIN OUTCOME MEASURE(S): Semistructured interviews explored men's
      experiences of father-only antenatal education groups. RESULTS: Four themes
      emerged from the thematic analysis: (i) motivations for attending antenatal
      groups; (ii) the effect of the group setting on men's experiences; (iii)
      masculine stereotypes in antenatal groups; and (iv) strategies to support
      fathers. Data show men wanted to join the groups and learn about being an
      involved father. They often felt uncomfortable sharing experiences in discussion
      based groups. They tended to prefer information-based groups which were not
      premised on sharing emotions. Men offered strategies to improve father-only
      antenatal education groups. CONCLUSION: Tasmanian antenatal education/support
      programs need improvement. Providing men with multiple opportunities to connect
      with other fathers is critical to improving support. Groups can be improved by
      accounting for multiple and complex constructions of masculinity, increasing the
      number of sessions offered and altering the structure.

PMID- 29218753
TI  - Neuronal responses to the scratching and caressing of one's own skin in patients
      with skin-picking disorder.
AB  - Skin-picking disorder (SPD) is a common mental disorder. The predominant symptom
      involves the repeated scratching and picking of one's own skin. This behavior
      causes severe tissue damage (sores, scars, and infections), often leading to
      disfigurement. Besides physical injury, SPD is associated with clinically
      significant distress and impairment in important areas of functioning. The
      neurobiological mechanisms of SPD are still poorly understood. In this study, 30
      SPD patients and 31 control participants (35 women, 26 men) with a mean age of 34
      years were instructed to either scratch or gently stroke a small skin area on
      their arms during functional magnetic resonance imaging. Gender-specific effects
      were revealed. In the female sample, SPD patients showed less activation in the
      middle frontal gyrus (MFG) and primary/secondary somatosensory cortices during
      caressing relative to scratching than controls. In addition, contrasting
      caressing with a rest condition revealed reduced activation in the somatosensory
      cortex (concerned with the decoding and integration of tactile information) and
      the MFG (attention/cognitive monitoring) in female patients. No differential
      brain activation was found in the male sample. This symptom provocation study
      hints at a reduced sensitivity of pleasant touch in women with SPD.

PMID- 29218754
TI  - Cutaneous leishmaniasis mimicking dactylitis in a patient with rheumatoid
      arthritis treated with certolizumab.

PMID- 29218755
TI  - Reducing Trap-Assisted Recombination in Small Organic Molecule-Based
      Photovoltaics by the Addition of a Conjugated Block Copolymer.
AB  - The performance of organic photovoltaics (OPVs) based on the small-molecule
      organic semiconductor p-DTS(FBTTh2 )2 is greatly improved by the addition of a
      conjugated block copolymer composed of difluoroquinoxaline and thienopyrrolodione
      blocks (D130). The power conversion efficiency (PCE) of the p-DTS(FBTTh2 )2 
      based OPV is improved from 5.08% to 6.75% by the addition of 5 wt% D130 to the
      photoactive layer, which is composed of p-DTS(FBTTh2 )2 and a fullerene
      derivative. Current-voltage and grazing incidence wide-angle X-ray scattering
      analyses revealed that the addition of D130 significantly reduces the trap
      density of the device and changes the packing orientation of p-DTS(FBTTh2 )2 from
      mostly edge-on to partially face-on. These changes greatly improve the charge
      carrier mobility of the OPV, indicating that D130 is highly compatible with p
      DTS(FBTTh2 )2 . Furthermore, the addition of D130 improve the photostability of
      the OPV by reducing the burn-in loss under a light soaking intensity of 1 sun.
      The D130-based OPV maintained 34% of its initial PCE after a light soaking test
      for 858 h. In contrast, the PCE of the OPV without D130 reduced to 14% of its
      initial efficiency in the same time period.

PMID- 29218756
TI  - Weight Suppression But Not Symptom Improvement Predicts Weight Gain During
      Inpatient Treatment for Bulimia Nervosa.
AB  - OBJECTIVE: Fear of gaining weight is a common obstacle to seeking treatment for
      bulimia nervosa (BN). We investigated changes in body mass index (BMI) during
      inpatient treatment for BN in relation to treatment outcome and weight
      suppression (WS). METHODS: Female inpatients of a specialized eating disorders
      clinic were grouped as deteriorated/unchanged, reliably improved, and clinically
      significantly improved based on Eating Disorder Inventory-2 scores. Repeated
      measures ANOVA was employed to examine changes in BMI between admission and
      discharge depending on treatment outcome and WS. RESULTS: One-hundred seventy
      nine patients were included. Overall, the average BMI significantly increased by
      0.54 kg/m2 (SD = 1.24). Repeated measures ANOVA revealed no association of change
      in BMI with treatment outcome [F(df) = 1.13 (2166), p = 0.327] but with WS [F(df)
      = 2.76 (3166), p < 0.044]. DISCUSSION: Bulimia nervosa can be successfully
      treated without causing excessive weight gain. Patients with higher WS might
      expect somewhat more weight gain. Copyright (c) 2017 John Wiley & Sons, Ltd and
      Eating Disorders Association.

PMID- 29218757
TI  - Local and global anatomy of antibody-protein antigen recognition.
AB  - Deciphering antibody-protein antigen recognition is of fundamental and practical
      significance. We constructed an antibody structural dataset, partitioned it into
      human and murine subgroups, and compared it with nonantibody protein-protein
      complexes. We investigated the physicochemical properties of regions on and away
      from the antibody-antigen interfaces, including net charge, overall antibody
      charge distributions, and their potential role in antigen interaction. We
      observed that amino acid preference in antibody-protein antigen recognition is
      entropy driven, with residues having low side-chain entropy appearing to
      compensate for the high backbone entropy in interaction with protein antigens.
      Antibodies prefer charged and polar antigen residues and bridging water
      molecules. They also prefer positive net charge, presumably to promote
      interaction with negatively charged protein antigens, which are common in
      proteomes. Antibody-antigen interfaces have large percentages of Tyr, Ser, and
      Asp, but little Lys. Electrostatic and hydrophobic interactions in the Ag binding
      sites might be coupled with Fab domains through organized charge and residue
      distributions away from the binding interfaces. Here we describe some features of
      antibody-antigen interfaces and of Fab domains as compared with nonantibody
      protein-protein interactions. The distributions of interface residues in human
      and murine antibodies do not differ significantly. Overall, our results provide
      not only a local but also a global anatomy of antibody structures.

PMID- 29218758
TI  - First evidence of bacterial translocation from the intestinal tract as a route of
      Helicobacter cinaedi bacteremia.
AB  - BACKGROUND: The route of Helicobacter cinaedi bacteremia has not yet been
      clarified. Although bacterial translocation from the intestinal tract into the
      circulation has been suggested, it has not been demonstrated thus far. The
      objective of this study was to investigate the port of entry of this bacterium.
      MATERIAL AND METHODS: We conducted a retrospective study on patients with H.
      cinaedi bacteremia between March 2009 and May 2013. Records of patients in whom
      H. cinaedi was detected in both blood and stool cultures were extracted. H.
      cinaedi was identified using gyrB-targeted PCR. Pulse-field gel electrophoresis
      was used to investigate the consistency of the genotypes. RESULTS: Seventy-one
      patients were diagnosed with H. cinaedi bacteremia during the study period. H.
      cinaedi was detected in both blood and stool samples of 21 patients. Pulse-field
      gel electrophoresis was used to investigate the consistency of the genotypes in
      18 evaluable strains (from 9 patients). The pulse-field gel electrophoresis
      patterns of the stool- and blood-derived strains of H. cinaedi were consistent
      among all 9 patients. Most of the 9 patients analyzed were immunocompromised and
      being treated with anticancer drugs or steroids, which suggests reduced
      intestinal immunity. CONCLUSIONS: This is the first study to demonstrate that
      bacterial translocation from the intestinal tract could represent one route of H.
      cinaedi bacteremia.

PMID- 29218759
TI  - Impact of pain and functional impairment in US adults with haemophilia: Patient
      reported outcomes and musculoskeletal evaluation in the pain, functional
      impairment and quality of life (P-FiQ) study.
AB  - INTRODUCTION: Standardized and disease-specific patient-reported outcome (PRO)
      instruments assessing pain, functional impairment and health-related quality of
      life (HRQoL) in people with haemophilia (PWH) have been used in studies, but
      infrequently in comprehensive care settings for individual assessment or
      treatment planning. AIM: To assess the impact of pain and functional impairment
      on HRQoL in PWH. METHODS: P-FiQ enrolled 381 adult PWH with a history of joint
      pain/bleeding and included 5 PROs and a clinical joint evaluation (Hemophilia
      Joint Health Score v2.1 [HJHS]). RESULTS: Median age was 34 years; 49.9% reported
      a history of joint procedure or surgery. On EQ-5D-5L, most reported problems with
      mobility (61.4%), usual activities (53.2%) and pain/discomfort (76.1%). On Brief
      Pain Inventory v2 Short Form, median worst pain (range 0-10) was 6, least pain 1,
      average pain 3 and current pain 2. Ankles were most frequently reported as the
      most painful joints (37.4%), followed by knees (23.7%) and elbows (18.9%). On
      International Physical Activity Questionnaire, 51% reported no activity in the
      prior week. On SF-36v2 health survey, median subscores were worse for 4 physical
      health domains vs 4 mental health domains. Among Hemophilia Activities List
      domains (range 0 [worst]-100 [best]), functions of the legs (median, 66.7) and
      lying/sitting/kneeling/standing (median, 67.5) were most impacted and self-care
      least impacted (median, 100.0). On HJHS, ankle scores (median, 6.0; range, 0-40)
      were worse than elbow/knee scores (median, 4.0/4.0). Results were consistent
      across PROs/HJHS. CONCLUSION: Data demonstrate challenges of predominantly
      ankle/knee pain and lower extremity functional impairment in US adult PWH,
      affecting HRQoL across PROs/HJHS.

PMID- 29218761
TI  - Naturalistic Outcome of Family-Based Inpatient Treatment for Adolescents with
      Anorexia Nervosa.
AB  - BACKGROUND: Outpatient family-based treatment (FBT) is the best-documented
      treatment for adolescent anorexia nervosa (AN), but research is scarce on FBT
      adapted to inpatient settings. AIM: The naturalistic outcome of inpatient FBT for
      adolescent AN was investigated. METHODS: Thirty-seven (65%) of 57 patients who
      received inpatient FBT at a tertiary adolescent eating disorders (ED) unit
      participated in a follow-up interview (mean 4.5 +/- 1.8, range 1-7 years) that
      assessed ED symptoms and general psychological functioning. RESULTS: A majority
      (65%) had achieved a normal body weight (body mass index >=18.5). Thirty-six per
      cent (n = 12) were classified as fully recovered, as defined by body mass index
      >=18.5, ED Examination Questionnaire global <=2.5, and no binge eating/purging
      over past 3 months. Sixteen (43%) participants met criteria for one or more
      additional comorbid disorders. CONCLUSION: Inpatient family-based therapy for AN
      may be a promising therapeutic approach for adolescents that fail to respond to
      outpatient treatment and should be investigated further. Copyright (c) 2017 John
      Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29218760
TI  - A systematic review of immunosuppressant adherence interventions in transplant
      recipients: Decoding the streetlight effect.
AB  - Non-adherence to immunosuppressant medications is an important risk factor for
      graft dysfunction. To evaluate the effectiveness of adherence-enhancing
      interventions, we reviewed adherence intervention studies in solid organ
      transplant recipients (all ages). Using the following databases: PsycINFO,
      PubMed, Scopus, and ScienceDirect, we identified 41 eligible studies. Only three
      non-randomized trials showed a possible positive effect on objective indicators
      of transplant outcomes (such as rejection, liver enzyme levels, kidney function).
      None of the 21 RCTs showed an improvement in transplant outcomes. Three studies
      showed a higher rate of adverse events in the intervention group as compared with
      controls, although this may be related to ascertainment bias. Improvement in
      adherence as measured indirectly (eg, with electronic monitoring devices) was not
      aligned with effects on transplant outcomes. We conclude that adherence
      interventions, to date, have largely been ineffective in improving transplant
      outcomes. To improve this track record, intervention efforts may wish to
      concentrate on non-adherent patients (rather than use convenience sampling, which
      excludes many of the patients who need the intervention), use direct measures of
      adherence to guide the interventions, and employ strategies that are intensive
      and yet engaging enough to ensure that non-adherent patients are able to
      participate.

PMID- 29218762
TI  - Comparison of paired and single clinical placement models: a time-use analysis.
AB  - BACKGROUND: To meet rising clinical placement demand caused by increasing health
      student numbers, the use of paired (two students) rather than single (one
      student) placement models has been proposed. There is, however, limited research
      available to inform placement providers about the relative effects of both models
      on healthcare services, including patient- and non-patient-related activities and
      patient occasions of service. AIMS: To investigate a key clinical question: Does
      clinical educator (supervisor) and student time use differ during paired
      placements compared with single placements? Also to examine the satisfaction
      levels of clinical educators (CEs) and students with paired and single clinical
      placement models. METHODS & PROCEDURES: Queensland Health speech and language
      therapists (N = 44) and speech and language therapy students (N = 32) involved in
      paired or single clinical placements were recruited for this study. CEs and
      students completed time-use surveys for 3 days after the midpoint of placements;
      CEs also completed surveys for 3 matched days during a non-placement period 3
      weeks or more following placements for comparative purposes. CEs and students
      additionally completed a satisfaction survey at the end of placements. Paired and
      single CE and student groups were compared for differences in their time-use and
      satisfaction levels using non-parametric statistics. OUTCOMES & RESULTS: The
      placement model did not impact on occasions of service provided by CEs (p =
      0.931) or students (p = 0.776). It also had no effect on the percentage of time
      CEs or students engaged in patient-related activities (p = 0.577; 0.291) and non
      patient-related activities (p = 0.559; 0.177). On clinical placement days, CEs
      spent a median 10 minutes longer at work regardless of whether or not it was a
      paired or single placement, compared with non-placement days (p = 0.107). CEs and
      students who had been involved in a paired placement reported the same high
      levels of placement satisfaction (various measures) as those who had been
      involved in a single placement. CONCLUSIONS & IMPLICATIONS: The paired-placement
      model has the potential to increase student placement offers without negatively
      impacting on clinical service provision including occasions of service, patient
      or non-patient-related activities, or overall CE time spent at work.

PMID- 29218763
TI  - Single-Cell Mass Spectrometry Approaches to Explore Cellular Heterogeneity.
AB  - Compositional diversity is a fundamental property in cell populations. Single
      cell analysis promises new insight into this cellular heterogeneity on the
      genomic, transcriptomic, proteomic, and metabolomic levels. Mass spectrometry
      (MS) is a label-free technique that enables the multiplexed analysis of proteins,
      peptides, lipids, and metabolites in individual cells. The abundances of these
      molecular classes are correlated with the physiological states and environmental
      responses of the cells. In this Minireview, we discuss recent advances in single
      cell MS techniques with an emphasis on sampling and ionization methods developed
      for volume-limited samples. Strategies for sample treatment, separation methods,
      and data analysis require special considerations for single cells. Ongoing
      analytical challenges include subcellular heterogeneity, non-normal statistical
      distributions of cellular properties, and the need for high-throughput, high
      molecular coverage and minimal perturbation.

PMID- 29218764
TI  - UK Dermatology specialist trainee career intentions.

PMID- 29218765
TI  - Deregulation of autophagy in postmortem brains of Machado-Joseph disease
      patients.
AB  - Autophagy, the major pathway for protein turnover, is critical to maintain
      cellular homeostasis and has been implicated in neurodegenerative diseases. The
      aim of this research was to analyze the expression of autophagy markers in
      postmortem brains from Machado-Joseph disease (MJD) patients. The expression of
      autophagy markers in the cerebellum and the oculomotor nucleus from MJD patients
      and age-matched controls with no signs of neuropathology was inspected postmortem
      by immunohistochemistry (IHC) and Western blot. Furthermore, autophagy was
      examined by means of transmission electron microscopy (TEM). Western blot and IHC
      revealed nuclear accumulation of misfolded ataxin-3 (ATXN3) and the presence of
      ubiquitin- and p62-positive aggregates in MJD patients as compared to controls.
      Moreover, the autophagic proteins, autophagy-related gene (Atg) protein (ATG)-7,
      ATG-12, ATG16L2 and autophagosomal microtubule-associated protein light chain 3
      (LC3) were significantly increased in MJD brains relative to controls, while
      beclin-1 levels were reduced in MJD patients. Increase in the levels of lysosomal
      associated membrane protein 2 (LAMP-2) and of the endosomal markers (Rab7 and
      Rab1A) were observed in MJD patients relatively to controls. In addition, these
      findings were further confirmed by TEM in brain tissue where large vesicles
      accumulating electron-dense materials were highly enriched in MJD patients.
      Postmortem brains with MJD exhibit increased markers of autophagy relative to age
      matched control brains, therefore suggesting strong dysregulation of autophagy
      that may have an important role in the course of MJD pathogenesis.

PMID- 29218766
TI  - Risk of recurrent severe hypoglycemia remains associated with a past history of
      severe hypoglycemia up to 4 years: Results from a large prospective contemporary
      pediatric cohort of the DPV initiative.
AB  - OBJECTIVES: In a contemporary cohort of youth with type 1 diabetes, we examined
      the interval between episodes of severe hypoglycemia (SH) as a risk factor for
      recurrent SH or hypoglycemic coma (HC). METHODS: This was a large longitudinal
      observational study. Using the DPV Diabetes Prospective follow-up data, we
      analyzed frequency and timing of recurrent SH (defined as requiring assistance
      from another person) and HC (loss of consciousness or seizures) in 14 177 youths
      with type 1 diabetes aged <20 years and at least 5 years of follow-up. RESULTS:
      Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1
      and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest
      with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]),
      but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI
      1.5-3.1]). The proportion of patients who experienced SH or HC during the last
      year of observation was highest with SH/HC recorded during the previous year (23%
      for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for
      HC) in the initial 4 years of observation. CONCLUSIONS: Even 4 years after an
      episode of SH/HC, risk for SH/HC remains higher compared to children who never
      experienced SH/HC. Clinicians should continue to regularly track hypoglycemia
      history at every visit, adjust diabetes education and therapy in order to avoid
      recurrences.

PMID- 29218767
TI  - Maternal communicative behaviours and interaction quality as predictors of
      language development: findings from a community-based study of slow-to-talk
      toddlers.
AB  - BACKGROUND: Identifying risk and protective factors for language development
      informs interventions for children with developmental language disorder (DLD).
      Maternal responsive and intrusive communicative behaviours are associated with
      language development. Mother-child interaction quality may influence how children
      use these behaviours in language learning. AIMS: To identify (1) communicative
      behaviours and interaction quality associated with language outcomes; (2) whether
      the association between a maternal intrusive behaviour (directive) and child
      language scores changed alongside a maternal responsive behaviour (expansion);
      and (3) whether interaction quality modified these associations. METHODS &
      PROCEDURES: Language skills were assessed at 24, 36 and 48 months in 197
      community-recruited children who were slow to talk at 18 months. Mothers and 24
      month-olds were video-recorded playing at home. Maternal praise, missed
      opportunities, and successful and unsuccessful directives (i.e., whether followed
      by the child) were coded during a 10-min segment. Interaction quality was rated
      using a seven-point fluency and connectedness (FC) scale, during a 5-min segment.
      Linear regressions examined associations between these behaviours/rating and
      language scores. Interaction analysis and simple slopes explored effect
      modification by FC. OUTCOMES & RESULTS: There was no evidence that missed
      opportunities or praise were associated with language scores. Higher rates of
      successful directives in the unadjusted model and unsuccessful directives in the
      adjusted model were associated with lower 24-month-old receptive language scores
      (e.g., unsuccessful directives effect size (ES) = -0.41). The association between
      unsuccessful directives and receptive language was weaker when adjusting for co
      occurring expansions (ES = -0.34). Both types of directives were associated with
      poorer receptive and expressive language scores in adjusted models at 36 and 48
      months (e.g., unsuccessful directive and 48-month receptive language, ES = 
      0.66). FC was positively associated with 24-, 36- and 48-month language scores in
      adjusted models (e.g., receptive language at 24 months, ES = 0.21, at 48 months,
      ES = 0.18). Interaction analysis showed the negative association between
      successful directives and 24-month receptive language existed primarily in poorly
      connected dyads with low FC levels. CONCLUSIONS & IMPLICATIONS: These findings
      illustrate the effects of the combined interaction between different maternal
      communicative behaviours and features of the interaction itself on child language
      development, and the need to consider both in research and practice. Whilst more
      intrusive directives were associated with poorer language scores, this
      association attenuated when adjusting for co-occurring responsive expansions, and
      the association was strongest for children in lower quality interactions. This
      work may inform clinical practice by helping clinicians target the most
      appropriate communicative behaviours for specific mother-child dyads.

PMID- 29218768
TI  - Relationships between serum brain-derived neurotrophic factor concentration and
      parameters for health scores in community-dwelling older adults.
AB  - AIM: Brain-derived neurotrophic factor (BDNF) have been implicated in the
      progression of neuronal survival, phenotyping differentiation and maintenance of
      various neurons, as well as neurogenesis. We studied how BDNF affects health
      parameters of older adults by carrying out a health examination of community
      dwelling older adults. METHODS: We measured the serum BDNF concentration of 898
      older adults aged 65-84 years who participated in regional health examinations in
      the Tokyo area and also measured various parameters, such as the thickness of the
      quadriceps femoris, percentage of body fat, body mass index, grip strength,
      frequency of walking, and use of sleeping drugs and steroidal anti-inflammatory
      drugs. RESULTS: We obtained significant relationships between serum BDNF values
      and thickness of the quadriceps muscle, body mass index or percentage of body
      fat. Individuals holding onto something when they stood up had lower serum BDNF
      values than individuals not holding onto something when they stood up. Smokers
      had higher serum BDNF values than non-smokers. CONCLUSIONS: Older adults who had
      higher serum BDNF had bigger quadriceps muscles, higher body mass index and
      higher body fat rate, and were also able to stand up without holding onto
      something from a sitting position. Geriatr Gerontol Int 2018; 18: 456-461.

PMID- 29218769
TI  - Current status on the development of pseudoviruses for enveloped viruses.
AB  - Emerging and reemerging infectious diseases have a strong negative impact on
      public health. However, because many of these pathogens must be handled in
      biosafety level, 3 or 4 containment laboratories, research and development of
      antivirals or vaccines against these diseases are often impeded. Alternative
      approaches to address this issue have been vigorously pursued, particularly the
      use of pseudoviruses in place of wild-type viruses. As pseudoviruses have been
      deprived of certain gene sequences of the virulent virus, they can be handled in
      biosafety level 2 laboratories. Importantly, the envelopes of these viral
      particles may have similar conformational structures to those of the wild-type
      viruses, making it feasible to conduct mechanistic investigation on viral entry
      and to evaluate potential neutralizing antibodies. However, a variety of
      challenging issues remain, including the production of a sufficient pseudovirus
      yield and the inability to produce an appropriate pseudotype of certain viruses.
      This review discusses current progress in the development of pseudoviruses and
      dissects the factors that contribute to low viral yields.

PMID- 29218770
TI  - Older Korean adults have lower physical function despite longer exercise times
      compared to their Japanese counterparts: A Japan-Korea comparative study.
AB  - AIM: We aimed to compare the level of physical function (PF) and habitual
      exercise between older Japanese and Korean adults. METHODS: A comparative study
      was carried out on 1069 community-dwelling older Japanese and Korean adults (mean
      age 73.9 +/- 5.2 years). The participants were asked to complete a self-reported
      questionnaire regarding habitual exercise and covariates. PF age, a composite
      measure of PF, was derived from the 12 items, using principal component analysis.
      PF age and habitual exercise were compared between the Japanese and Korean
      adults, using analysis of covariance (ancova) and multivariable logistic
      regression analysis adjusted for all covariates using propensity scores. RESULTS:
      ancova showed that PF age in older Japanese adults was significantly younger than
      in their Korean counterparts. Older Japanese adults exercised significantly less
      frequently than their Korean counterparts. Furthermore, older Japanese adults
      practiced significantly less walking, mountain climbing and bicycling, but more
      calisthenics, resistance training, ball games and dances than their Korean
      counterparts. CONCLUSIONS: We found that older Korean adults had lower PF (3.7
      years older in PF age) than their Japanese counterparts. Although the overall
      frequency and amount of habitual exercise in older Korean adults were higher than
      those in their Japanese counterparts, particular types of exercise might have
      contributed to the higher PF levels among older Japanese adults. Thus, older
      Korean adults might need to engage more in habitual exercises that are
      specifically effective in maintaining PF. Geriatr Gerontol Int 2018; 18: 576-583.

PMID- 29218771
TI  - Menopause-Related Appendicular Bone Loss is Mainly Cortical and Results in
      Increased Cortical Porosity.
AB  - After menopause, remodeling becomes unbalanced and rapid. Each of the many
      remodeling transactions deposits less bone than it resorbed, producing
      microstructural deterioration. Trabecular bone is said to be lost more rapidly
      than cortical bone. However, because 80% of the skeleton is cortical, we
      hypothesized that most menopause-related bone loss and changes in bone
      microstructure are cortical, not trabecular in origin, and are the result of
      intracortical remodeling. Distal tibial and distal radial microstructure were
      quantified during 3.1 years (range, 1.5 to 4.5 years) of follow-up using high
      resolution peripheral quantitative computed tomography and StrAx software in 199
      monozygotic and 125 dizygotic twin pairs aged 25 to 75 years in Melbourne,
      Australia. The annual increases in tibial cortical porosity accelerated, being
      0.44%, 0.80%, and 1.40% in women remaining premenopausal, transitioning to
      perimenopause, and from perimenopausal to postmenopause, respectively. Porosity
      increased in the compact-appearing, outer, and inner transitional zones of the
      cortex (all p < 0.001). The annual decrease in trabecular bone volume/tissue
      volume (BV/TV) also accelerated, being 0.17%, 0.26%, and 0.31%, respectively.
      Little bone loss was observed before menopause. The reduction in BV/TV was due to
      a decrease in trabecular number (p < 0.001). The greatest bone loss, 7.7 mg
      hydroxyapatite (HA) annually, occurred in women transitioning from perimenopausal
      to postmenopause and of this, 6.1 mg HA (80%) was cortical. Results were similar
      for the distal radius. Despite microarchitectural changes, no significant bone
      loss was observed before menopause. Over 90% of appendicular bone loss occurs
      during and after menopause, over 80% is cortical, and this may explain why 80% of
      fractures are appendicular. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 29218772
TI  - Signals for identifying cows at risk of subacute ruminal acidosis in dairy
      veterinary practice.
AB  - Controlling rumen disorders is critical to ensure successful dairy herd health
      management. Lactation diets of dairy cows are commonly rich in concentrates and
      low in physically effective fibre. Feeding of these diets increases the risk of
      rumen disorders with far-reaching consequences for cattle health, welfare and
      sustainability of dairy production. The term subacute ruminal acidosis or SARA is
      often used as a synonym for poor rumen health. Being subclinical, SARA lacks of
      clear symptoms and is therefore difficult to diagnose and to control in the
      practice. This review article summarises common and identifies new direct and
      indirect cow signals related to SARA. We have performed a scientific evaluation
      and interpretation of each of these cow signals by highlighting their advantages
      and disadvantages from the practitioner's point of view. The gold standard of
      SARA cow signals still remains direct measurement of ruminal pH. However,
      continuous pH monitoring is cost-intensive and often biased by sensor drift.
      Single-point ruminal pH measurements by oral stomach tubing or rumenocentesis
      have strong limitations. Therefore, there is a need for reliable and robust
      markers of SARA that are easily accessible and inexpensive. Such indirect
      parameters are the observation of chewing and feeding activities, as well as the
      monitoring of milk, faecal, urine and blood variables. Also, novel technologies
      that allow rapid and non-invasive measurement of the rumen mucosa thickness and
      ruminal motility patterns might provide advantages in SARA diagnosis. Due to
      several constraints of these indirect diagnostic tools, such as limited
      specificity and sensitivity, we strongly recommend using a combination of the
      signals to reliably identify cows at risk of SARA in a dairy herd.

PMID- 29218774
TI  - Impact of anti-infective periodontal therapy on parameters of vascular health.
AB  - AIM: This study assessed the impact of anti-infective periodontal therapy on the
      status of vascular health. MATERIALS AND METHODS: Periodontal and vascular health
      of 55 patients with severe untreated chronic periodontitis was evaluated before
      and 12 months after anti-infective periodontal therapy. Observed parameters were
      bleeding on probing (BoP), pocket probing depth (PPD), periodontal inflamed
      surface area index (PISA), pulse wave velocity (PWV), augmentation index (AIx),
      central pulse pressure (PPao) and peripheral systolic pressure (RRsys). RESULTS:
      DeltaPISA (baseline-12 months) correlated with DeltaPWV (tau 0.21; p < .03),
      DeltaAIx (tau 0.29; p < .002) and DeltaPPao (tau 0.23; p < .02). DeltaBoP%
      (baseline-12 months) correlated with DeltaPWV (tau 0.18; p < .05) and DeltaAIx
      (tau 0.25; p < .01), while mean DeltaPPD (baseline-12 months) correlated with
      DeltaPWV (tau 0.24; p < .01) and DeltaAIx (tau 0.21; p < .03). Grouping patients
      evenly into three groups based on tertiles of BoP resolution after 12 months
      revealed a significant decrease in the observed PWV median value by -0.6 m/s (p <
      .04) in the best response tertile (DeltaBoP >= 88%). In the worst response
      tertile (DeltaBoP <= 66%), by contrast, significant increase in PPao (+10.5 mmHg;
      p < .02) and AIx (+5.5; p < .02) was observed. CONCLUSION: Efficacious resolution
      of periodontal inflammation may beneficially impact on vascular health.

PMID- 29218775
TI  - Comparative proteomic analysis of silver nanoparticle effects in human liver and
      intestinal cells.
AB  - Consumers are orally exposed to nanoparticulate or soluble species of the non
      essential element silver due to its use in food contact materials or as a food
      additive. Potential toxicity of silver nanoparticles has gained special
      scientific attention. A fraction of ingested ionic or particulate silver is taken
      up in the intestine and transported to the liver, where it may induce oxidative
      stress and elicit subsequent adverse responses. Here, we present a comprehensive
      analysis of global proteomic changes induced in human Hep G2 hepatocarcinoma
      cells by different concentrations of AgPURE silver nanoparticles or by
      corresponding concentrations of ionic silver. Bioinformatic analysis of proteomic
      data confirms and substantiates previous findings on silver-induced alterations
      related to redox stress, mitochondrial dysfunction, intermediary metabolism,
      inflammatory responses, posttranslational protein modification and other cellular
      parameters. Similarities between the effects exerted by the two silver species
      are in line with the assumption that silver ions released from nanoparticles
      substantially contribute to their toxicity. Moreover, a comparative bioinformatic
      evaluation of proteomic effects in hepatic and intestinal cells exerted either by
      silver nanoparticles or bionic silver is presented. Our results show that,
      despite remarkable differences at the level of affected proteins in the different
      cell lines, highly similar biological consequences, corresponding to previous in
      vivo findings, can be deduced by applying appropriate bioinformatic data mining.

PMID- 29218773
TI  - Illness and end-of-life experiences of children with cancer who receive
      palliative care.
AB  - BACKGROUND: The field of pediatric palliative oncology is newly emerging. Little
      is known about the characteristics and illness experiences of children with
      cancer who receive palliative care (PC). METHODS: A retrospective cohort study of
      321 pediatric oncology patients enrolled in PC who died between 2011 and 2015 was
      conducted at a large academic pediatric cancer center using a comprehensive
      standardized data extraction tool. RESULTS: The majority of pediatric palliative
      oncology patients received experimental therapy (79.4%), with 40.5% enrolled on a
      phase I trial. Approximately one-third received cancer-directed therapy during
      the last month of life (35.5%). More than half had at least one intensive care
      unit hospitalization (51.4%), with this subset demonstrating considerable
      exposure to mechanical ventilation (44.8%), invasive procedures (20%), and
      cardiopulmonary resuscitation (12.1%). Of the 122 patients who died in the
      hospital, 44.3% died in the intensive care unit. Patients with late PC
      involvement occurring less than 30 days before death had higher odds of dying in
      the intensive care unit over the home/hospice setting compared to those with
      earlier PC involvement (OR: 4.7, 95% CI: 2.47-8.97, P < 0.0001). CONCLUSIONS:
      Children with cancer who receive PC experience a high burden of intensive
      treatments and often die in inpatient intensive care settings. Delayed PC
      involvement is associated with increased odds of dying in the intensive care
      unit. Prospective investigation of early PC involvement in children with high
      risk cancer is needed to better understand potential impacts on cost
      effectiveness, quality of life, and delivery of goal concordant care.

PMID- 29218776
TI  - Is the consumption of snail meat actually healthy? An analysis of the osteotropic
      influence of snail meat as a sole source of protein in growing rats.
AB  - The study was aimed at determining the osteotropic effects of diets containing
      snail meat as a sole protein source. In our experiment, we tested three different
      diets incorporating snail meat originating from Helix pomatia (HP), Cornu.aspesa
      maxima (CAM) and Cornu.aspersum aspersum (CAA) and compared these to a control
      diet (CON) in which casein was the source of protein. In all diets, the protein
      content amounted to 10%, as calculated on a dry weight basis. In the study, forty
      male Wistar rats with an initial body mass of 50 +/- 2 g were randomly placed
      within the control and three experimental groups. After 28 days of experimental
      feeding, the rats were sacrificed, and the body mass, total skeletal density and
      body composition were recorded. Moreover, blood serum (osteocalcin, CTX) and
      isolated tibia (pQCT, DXA, 3D micro-CT, 3-point bending test) were stored for
      further analysis. The results reveal that a diet incorporating snail meat
      significantly decreased BMC (bone mineral content), as well as area of total
      skeleton and isolated tibia, and was without influence on BMD (bone mineral
      density). Furthermore, the 3D micro-CT analysis of trabecular compartment
      documented a reduced Tb.Th (trabecular thickness), as well as Tb.N (trabecular
      number), and an increased Tb.Sp (trabecular separation). Beyond the
      aforementioned, the snail-based diets had an influence upon the architectonical
      properties of the tibia-decreasing its resistance to mechanical loading. Finally,
      snail meat, when used as an alone source of protein, negatively influenced the
      metabolism of the bone tissue in growing animals-making bone smaller and weaker.

PMID- 29218777
TI  - Decision making in pediatric hematopoietic cell transplantation: Influential
      factors vary among diseases.
AB  - Hematopoietic cell transplantation (HCT) is not a trivial treatment decision in
      pediatrics. We sought to understand what influences this decision-making process
      from the perspectives of the pediatric patients, their family, and physicians.
      Using integrative review methods, we identified 19 relevant studies: six
      qualitative, ten quantitative, and three mixed methods. Synthesis of the results
      revealed six themes describing patient, family, and provider decision-making
      processes with distinct subthemes contrasting influential factors among malignant
      and nonmalignant diseases. Identification of what influences HCT decision making
      will aid in development of decision support, education, and communication
      strategies. The child/adolescent voice and provider perspective warrant more
      attention.

PMID- 29218778
TI  - Examination of sacral tissue oxygen saturation among immobile patients.
AB  - AIMS AND OBJECTIVES: To explore the effect of immobility on sacral tissue oxygen
      saturation in patients lying on a supporting surface in supine position.
      BACKGROUND: Guidelines in regard to preventing pressure ulcers recommend that
      patients lying on a standard bed should change their positions every 2 hr and
      that patients on a supporting surface should change their positions every 4 hr.
      But there is no strong evidence that justifies this practice. DESIGN: Quasi
      experimental. METHODS: Data for the research were collected over the period
      October 2014-March 2015 at Anesthesiology and Reanimation and Neurosurgery Clinic
      Intensive Care Units. A total of 46 patients matching the research criteria were
      left in the supine position for 4 hr without having a position change, during
      which time sacral tissue oxygen saturation was measured every hour on the hour.
      Sacral tissue oxygen saturation was measured with the InSpectra Tissue
      Oxygenation Monitor. RESULTS: Mean sacral tissue oxygen saturation was 73.4% at
      baseline and was then measured as 74.9% at the first hour, 72.3% at the second
      hour, 71.9% at the third hour and 71.9% at the fourth hour. The changes observed
      between measuring times were not found to be statistically significant (p = .09).
      CONCLUSIONS: No statistically significant differences were found between sacral
      tissue oxygen saturation values recorded over a period of 4 hr in immobile
      patients lying on a supporting surface in the supine position. However, it was
      observed that sacral tissue oxygen saturation values did not change significantly
      depending upon the type of supporting surface that was being used. RELEVANCE TO
      CLINICAL PRACTICE: The study outcome supports changing the position of a patient
      lying on a supporting surface every 4 hr and provides evidence that justifies the
      recommendation made in the guidelines.

PMID- 29218779
TI  - Association between global functioning at first schizophrenia diagnosis and
      treatment resistance.
AB  - AIM: Several factors such as age, gender, urbanicity and clinical treatment
      setting have been associated with treatment-resistant schizophrenia (TRS). We
      examined the association between the Global Assessment of Functioning (social
      Functioning [GAF-F]) score at first schizophrenia diagnosis and TRS and explored
      whether level of functioning could partially explain the known associations.
      METHODS: A nationwide population-based cohort study among individuals, who had a
      GAF-F score at first schizophrenia diagnosis. We used adjusted Cox regression
      analysis to calculate hazard ratios (HRs). RESULTS: Among 3252 individuals,
      severe functional impairment (GAF-F <= 30) was associated with TRS within 2 years
      after diagnosis (adjusted HR = 1.38 [95% confidence interval: 1.03-1.87). GAF-F
      had virtually no impact on the associations between investigated known risk
      factors and TRS. CONCLUSIONS: GAF-F was independently associated with TRS.
      Consideration of a global functioning score may help clinicians to detect
      treatment resistance earlier among individuals with schizophrenia.

PMID- 29218780
TI  - Undertreatment of hypertension and hypercholesterolaemia in children and
      adolescents with type 1 diabetes: long-term follow-up on time trends in the
      occurrence of cardiovascular disease, risk factors and medications use.
AB  - AIMS: The aims of the present study were, firstly, to evaluate long-term trends
      in the occurrence and treatment of cardiovascular disease (CVD) risk factors and
      the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM)
      and, secondly, to assess the determinants of undertreatment of CVD risk factors.
      METHODS: A retrospective cohort study was conducted in 3728 children (<19 years
      of age) with T1DM and up to 5 age- and gender-matched diabetes-free children
      (reference cohort) (n = 18 513) using data from the Clinical Practice Research
      Datalink (CPRD). RESULTS: Compared with diabetes-free subjects, children with
      T1DM had significantly higher annual prevalence rates of CVD risk factors and
      cardiovascular (CV) medication use 20 years after the onset of diabetes (index
      date): hypertension: 35.2% vs. 11.4%, P < 0.001; hypercholesterolaemia: 66.7% vs.
      7.14%, P < 0.001; and CV medication use: 37.0% vs. 3.6%, P < 0.001. The
      significant differences between prevalence rates in the two cohorts started from
      1 year before the index date. Furthermore, 50% of the children in the T1DM cohort
      with hypertension and 53% with hypercholesterolaemia remained untreated with CV
      drugs for a period of 2-5 years during the 20-year follow-up. Age was the only
      determinant associated with undertreated hypertension in the T1DM cohort.
      CONCLUSIONS: Children with T1DM had substantially higher prevalence rates of
      hypertension and hypercholesterolaemia from 1 year before up to 20 years after
      the onset of diabetes compared with nondiabetics. There is a substantial
      undertreatment of CVD risk factors with CV drugs. In children with T1DM,
      screening for CVD risk factors and adequate treatment are of the utmost
      importance to prevent CVD later in life.

PMID- 29218781
TI  - In vitro invasion capacity of Salmonella Typhimurium DT9 isolates sourced from
      humans and layer hen environments.
AB  - In Australia, Salmonella Typhimurium definitive type 9 is frequently isolated
      during foodborne outbreaks of salmonellosis. Multiple-locus variable number
      tandem repeat analysis (MLVA) trace back investigations frequently identify
      isolate distribution patterns that may be epidemiologically linked to disease
      outbreaks. In this study, the in vitro virulence potential of S. Typhimurium DT9
      isolates possessing different MLVA patterns (03 15 07 11 550, 03 24 11 10 523, 03
      15 08 11 550 and 03 14 08 11 550) isolated from either humans or layer hens was
      assessed using a human colon carcinoma cell line. Four strains per MLVA from each
      host for a total of 32 isolates were included in these experiments. Bacteria were
      grown to stationary phase and added to cells at a multiplicity of infection of
      100. Across all isolates, mean percent recovery ranged from 7.1 +/- 1.1 to 33.3
      +/- 7.1%. The layer hen isolate, KC900 (MLVA profile 03 15 08 11 550), exhibited
      the greatest invasion with a mean percent recovery of 33.3 +/- 7.1%. Overall,
      layer hen isolates of S. Typhimurium DT9 had significantly higher invasion into
      Caco2 cells than human isolates (p = .0021). RAPD and enterobacterial repetitive
      intergenic consensus genomic fingerprinting was also performed. Irrespective of
      source, the SalmonellaDT9 isolates included in this study exhibited similar
      fingerprint patterns.

PMID- 29218783
TI  - Magnetic iron oxide nanoparticles (MIONs) cross-linked natural polymer-based
      hybrid gel beads: Controlled nano anti-TB drug delivery application.
AB  - The nanosized rifampicin (RIF) has been prepared to increase the solubility in
      aqueous solution, which leads to remarkable enhancement of its bioavailability
      and their convenient delivery system studied by newly produced nontoxic,
      biodegradable magnetic iron oxide nanoparticles (MIONs) cross-linked polyethylene
      glycol hybrid chitosan (mCS-PEG) gel beads. The functionalization of both nano
      RIF and mCS-PEG gel beads were studied using various spectroscopic and
      microscopic techniques. The size of prepared nano RIF was found to be 70.20 +/-
      3.50 nm. The mechanical stability and swelling ratio of the magnetic gel beads
      increased by the addition of PEG with a maximum swelling ratio of 38.67 +/- 0.29
      g/g. Interestingly, this magnetic gel bead has dual responsive assets in the nano
      drug delivery application (pH and the magnetic field). As we expected, magnetic
      gel beads show higher nano drug releasing efficacy at acidic medium (pH = 5.0)
      with maximum efficiency of 71.00 +/- 0.87%. This efficacy may also be tuned by
      altering the external magnetic field and the weight percentage (wt%) of PEG.
      These results suggest that such a dual responsive magnetic gel beads can be used
      as a potential system in the nano drug delivery applications. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1039-1050, 2018.

PMID- 29218784
TI  - Intraspecific genetic structure, divergence and high rates of clonality in an
      amphi-Atlantic starfish.
AB  - Intraspecific genetic diversity and divergence have a large influence on the
      adaption and evolutionary potential of species. The widely distributed starfish,
      Coscinasterias tenuispina, combines sexual reproduction with asexual reproduction
      via fission. Here we analyse the phylogeography of this starfish to reveal
      historical and contemporary processes driving its intraspecific genetic
      divergence. We further consider whether asexual reproduction is the most
      important method of propagation throughout the distribution range of this
      species. Our study included 326 individuals from 16 populations, covering most of
      the species' distribution range. A total of 12 nuclear microsatellite loci and
      sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene were
      analysed. COI and microsatellites were clustered in two isolated lineages: one
      found along the southwestern Atlantic and the other along the northeastern
      Atlantic and Mediterranean Sea. This suggests the existence of two different
      evolutionary units. Marine barriers along the European coast would be responsible
      for population clustering: the Almeria-Oran Front that limits the entrance of
      migrants from the Atlantic to the Mediterranean, and the Siculo-Tunisian strait
      that divides the two Mediterranean basins. The presence of identical genotypes
      was detected in all populations, although two monoclonal populations were found
      in two sites where annual mean temperatures and minimum values were the lowest.
      Our results based on microsatellite loci showed that intrapopulation genetic
      diversity was significantly affected by clonality whereas it had lower effect for
      the global phylogeography of the species, although still some impact on
      populations' genetic divergence could be observed between some populations.

PMID- 29218785
TI  - Increased affinity of endothelial cells to NiTi using ultraviolet irradiation: An
      in vitro study.
AB  - Nickel-titanium alloy (NiTi) is one of the most popular materials used
      endovascularly because of its shape memory and superelasticity. The NiTi device
      needs to be covered by endothelial cells after being placed in the blood vessel
      to reduce ischemic complications. The objective of this study was to examine the
      impact of ultraviolet (UV) irradiation on the biocompatibility of NiTi surfaces
      with endothelial cells. NiTi sheets were treated with UV irradiation for 48 h and
      human aorta derived endothelial cells were used in this study. UV irradiation
      converted the NiTi surface to hydrophilic state and increased albumin adsorption.
      The number of endothelial cell migration, attachment, proliferation as well as
      their metabolic activity were significantly increased on UV treated NiTi. This
      study provides the first evidence of the photoactivation of NiTi surfaces by UV
      irradiation and demonstrates improved biocompatibility of UV-treated NiTi
      surfaces with vascular endothelial cells. These results suggest that UV
      irradiation may promote endothelialization of NiTi devices in blood vessels. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1034-1038, 2018.

PMID- 29218786
TI  - How fast can treatment with overdentures improve the masticatory function and
      OHRQoL of atrophic edentulous patients? A 1-year longitudinal clinical study.
AB  - OBJECTIVES: The aim of this prospective clinical study was to evaluate the
      masticatory function (MF) and subjective perception of patients with poor denture
      bearing tissue in relation to change and the time required to identify an
      improvement in these parameters after rehabilitation with mandibular overdentures
      (MO) by two narrow-diameter two-piece implants. MATERIAL AND METHODS: Twenty
      three edentulous patients were selected for MO installation. The masticatory
      function (MF) was evaluated with the masticatory performance (MP) and swallowing
      threshold (ST) tests. In the MP test, each volunteer was instructed to masticate
      a portion of Optocal (standardized artificial test food) for 40 masticatory
      cycles. During the swallowing threshold test, the patients were instructed to
      chew a new portion of Optocal cubes until they felt the desire to swallow. The MF
      tests were performed while complete denture (CD) wearers (baseline) and 1, 3, 6,
      and 12 months after MO loading. In addition, the subjective perception was
      assessed through the questionnaires Dental Impact on Daily Living (DIDL),
      Geriatric Oral Health Assessment Index (GOHAI), and Oral Health Impact Profile in
      Edentulous (OHIP- EDENT) at the baseline and 3, 6, and 12 months after MO
      loading. RESULTS: A significant improvement in masticatory function (p < .05) was
      observed already in the first month of loading. Three months after MO loading, a
      significant improvement (p < .05) was found in the subjective perception of
      patients. The effect size indicates that the MO had the greatest impact on the
      domains related to function and comfort of all questionnaires and in relation to
      psychosocial domain of the GOHAI. The level of patient satisfaction increased
      significantly after the MO loading and reached >90% satisfied patients at 12
      months. CONCLUSION: The MO improved both the MF of the patient and their oral
      health-related quality of life and satisfaction regarding the prosthesis in a
      short time period.

PMID- 29218782
TI  - Therapy development in Huntington disease: From current strategies to emerging
      opportunities.
AB  - Huntington disease (HD) is a progressive autosomal dominant neurodegenerative
      disorder in which patients typically present with uncontrolled involuntary
      movements and subsequent cognitive decline. In 1993, a CAG trinucleotide repeat
      expansion in the coding region of the huntingtin (HTT) gene was identified as the
      cause of this disorder. This extended CAG repeat results in production of HTT
      protein with an expanded polyglutamine tract, leading to pathogenic HTT protein
      conformers that are resistant to protein turnover, culminating in cellular
      toxicity and neurodegeneration. Research into the mechanistic basis of HD has
      highlighted a role for bioenergetics abnormalities stemming from mitochondrial
      dysfunction, and for synaptic defects, including impaired neurotransmission and
      excitotoxicity. Interference with transcription regulation may underlie the
      mitochondrial dysfunction. Current therapies for HD are directed at treating
      symptoms, as there are no disease-modifying therapies. Commonly prescribed drugs
      for involuntary movement control include tetrabenazine, a potent and selective
      inhibitor of vesicular monoamine transporter 2 that depletes synaptic monoamines,
      and olanzapine, an atypical neuroleptic that blocks the dopamine D2 receptor.
      Various drugs are used to treat non-motor features. The HD therapeutic pipeline
      is robust, as numerous efforts are underway to identify disease-modifying
      treatments, with some small compounds and biological agents moving into clinical
      trials. Especially encouraging are dosage reduction strategies, including
      antisense oligonucleotides, and molecules directed at transcription
      dysregulation. Given the depth and breadth of current HD drug development
      efforts, there is reason to believe that disease-modifying therapies for HD will
      emerge, and this achievement will have profound implications for the entire
      neurotherapeutics field.

PMID- 29218787
TI  - Waist circumference at five common measurement sites in normal weight and
      overweight adults: which site is most optimal?
AB  - The aim of this study was to determine (i) if adults would measure their own
      waist circumference (WC), (ii) which WC site(s) are the most intuitive and easy
      to measure and (iii) if measurement accuracy and association between WC and blood
      pressure differs across five measurement sites. Participants (n = 198) measured
      their WC first with no instruction and then using visual instructions for the
      iliac crest, last rib, midpoint, minimal waist and umbilicus. Without
      instruction, men most commonly measured their WC at the umbilicus and iliac
      crest, while women measured their WC at the umbilicus and minimal WC. Both men
      and women reported the minimal waist and umbilicus to be moderately easier to
      self-measure compared to the other sites (P < 0.05). Prevalence of abdominal
      obesity varied significantly by gender and measurement site, especially for
      females (normal weight: 0-18%; overweight: 51-79%). Measurement site did not
      influence accuracy of WC self-measurement or the association between WC and blood
      pressure (P > 0.05). A universal WC landmark is needed. From these results, there
      does not appear to be a clear clinical advantage in terms of blood pressure or
      practical advantage of measuring one WC site over another. However, the umbilicus
      may be the most intuitive and easy to measure.

PMID- 29218788
TI  - Alternative Solutions to a Language Design Problem: The Role of Adjectives and
      Gender Marking in Efficient Communication.
AB  - A central goal of typological research is to characterize linguistic features in
      terms of both their functional role and their fit to social and cognitive
      systems. One long-standing puzzle concerns why certain languages employ
      grammatical gender. In an information theoretic analysis of German noun
      classification, Dye, Milin, Futrell, and Ramscar (2017) enumerated a number of
      important processing advantages gender confers. Yet this raises a further puzzle:
      If gender systems are so beneficial to processing, what does this mean for
      languages that make do without them? Here, we compare the communicative function
      of gender marking in German (a deterministic system) to that of prenominal
      adjectives in English (a probabilistic one), finding that despite their
      differences, both systems act to efficiently smooth information over discourse,
      making nouns more equally predictable in context. We examine why evolutionary
      pressures may favor one system over another and discuss the implications for
      compositional accounts of meaning and Gricean principles of communication.

PMID- 29218789
TI  - Precise localizations of voltage-gated sodium and potassium channels in neurons.
AB  - Neurons are extremely large and complex cells, and they regulate membrane
      potentials in multiple subcellular compartments using a variety of ion channels.
      Voltage-gated sodium (Nav) and potassium (Kv) channels are crucial in regulating
      neuronal membrane excitability owing to their diversity in subtypes, biophysical
      properties, and localizations. In particular, specific localizations of Nav and
      Kv channels in specific membrane compartments are essential to achieve a precise
      control of local membrane excitability. Recent advancement in super-resolution
      microscopy further substantiated nanoscale localizations of different ion
      channels in neuronal membranes. New questions arise from these new lines of
      evidence regarding how Nav and Kv channels are trafficked to a specific location
      and maintained against lateral diffusion. In this review, the aim is to summarize
      current information about ion channel localizations at nanoscopic levels and
      discuss what we can infer regarding the mechanisms. (c) 2017 Wiley Periodicals,
      Inc. Develop Neurobiol 78: 271-282, 2018.

PMID- 29218790
TI  - Embolic strokes of undetermined source in young adults: baseline characteristics
      and long-term outcome.
AB  - BACKGROUND AND PURPOSE: Embolic strokes of undetermined source (ESUS) are a
      recent entity, not yet thoroughly investigated in young stroke patients. The
      clinical characteristics and long-term risks of vascular events and all-cause
      mortality between young-onset ESUS and other aetiological subgroups were
      compared. METHODS: Patients with ESUS were identified amongst the 1008 patients
      aged 15-49 years with first-ever ischaemic stroke in Helsinki Young Stroke
      Registry, and primary end-points were defined as recurrent stroke, composite
      vascular events and all-cause mortality. Cumulative 15-year risks for each end
      point were analysed with life tables and adjusted risks were based on Cox
      proportional hazard analyses. RESULTS: Of the 971 eligible patients, 203 (20.9%)
      were classified as ESUS. They were younger (median age 40 years, interquartile
      range 32-46 vs. 45 years, 39-47), more often female (43.3% vs. 35.7%) and had
      fewer cardiovascular risk factors than other modified TOAST groups. With a median
      follow-up time of 10.1 years, ESUS patients had the second lowest cumulative risk
      of recurrent stroke and composite vascular events and lowest mortality compared
      to other TOAST groups. Large-artery atherosclerosis and small vessel disease
      carried significantly higher risk for recurrent stroke than did ESUS, whilst no
      difference appeared between cardioembolism from high-risk sources and ESUS.
      CONCLUSIONS: In our cohort, ESUS patients were younger and had milder
      cardiovascular risk factor burden and generally better long-term outcome compared
      to other causes of young-onset stroke. The comparable risk of recurrent stroke
      between ESUS and high-risk sources of cardioembolism might suggest similarities
      in their pathophysiology.

PMID- 29218792
TI  - Complex selection on a regulator of social cognition: Evidence of balancing
      selection, regulatory interactions and population differentiation in the prairie
      vole Avpr1a locus.
AB  - Adaptive variation in social behaviour depends upon standing genetic variation,
      but we know little about how evolutionary forces shape genetic diversity relevant
      to brain and behaviour. In prairie voles (Microtus ochrogaster), variants at the
      Avpr1a locus predict expression of the vasopressin 1a receptor in the
      retrosplenial cortex (RSC), a brain region that mediates spatial and contextual
      memory; cortical V1aR abundance in turn predicts diversity in space use and
      sexual fidelity in the field. To examine the potential contributions of adaptive
      and neutral forces to variation at the Avpr1a locus, we explore sequence
      diversity at the Avpr1a locus and throughout the genome in two populations of
      wild prairie voles. First, we refine results demonstrating balancing selection at
      the locus by comparing the frequency spectrum of variants at the locus to a
      random sample of the genome. Next, we find that the four single nucleotide
      polymorphisms that predict high V1aR expression in the RSC are in stronger
      linkage disequilibrium than expected by chance despite high recombination among
      intervening variants, suggesting that epistatic selection maintains their
      association. Analysis of population structure and a haplotype network for two
      populations revealed that this excessive LD was unlikely to be due to admixture
      alone. Furthermore, the two populations differed considerably in the region shown
      to be a regulator of V1aR expression despite the extremely low levels of
      genomewide genetic differentiation. Together, our data suggest that complex
      selection on Avpr1a locus favours specific combinations of regulatory
      polymorphisms, maintains the resulting alleles at population-specific
      frequencies, and may contribute to unique patterns of spatial cognition and
      sexual fidelity among populations.

PMID- 29218791
TI  - A novel approach to training attention and gaze in ASD: A feasibility and
      efficacy pilot study.
AB  - In addition to the social, communicative and behavioral symptoms that define the
      disorder, individuals with ASD have difficulty re-orienting attention quickly and
      accurately. Similarly, fast re-orienting saccadic eye movements are also
      inaccurate and more variable in both endpoint and timing. Atypical gaze and
      attention are among the earliest symptoms observed in ASD. Disruption of these
      foundation skills critically affects the development of higher level cognitive
      and social behavior. We propose that interventions aimed at these early deficits
      that support social and cognitive skills will be broadly effective. We conducted
      a pilot clinical trial designed to demonstrate the feasibility and preliminary
      efficacy of using gaze-contingent video games for low-cost in-home training of
      attention and eye movement. Eight adolescents with ASD participated in an 8-week
      training, with pre-, mid- and post-testing of eye movement and attention control.
      Six of the eight adolescents completed the 8 weeks of training and all six showed
      improvement in attention (orienting, disengagement) and eye movement control or
      both. All game systems remained intact for the duration of training and all
      participants could use the system independently. We delivered a robust, low-cost,
      gaze-contingent game system for home use that, in our pilot training sample,
      improved the attention orienting and eye movement performance of adolescent
      participants in 8 weeks of training. We are currently conducting a clinical trial
      to replicate these results and to examine what, if any, aspects of training
      transfer to more real-world tasks. (c) 2017 Wiley Periodicals, Inc. Develop
      Neurobiol 78: 546-554, 2018.

PMID- 29218793
TI  - Anti-proliferation effect of blue light-emitting diodes against antibiotic
      resistant Helicobacter pylori.
AB  - BACKGROUND AND AIM: Infection by Helicobacter pylori is implicated in a wide
      range of upper gastrointestinal diseases. Owing to the rapid emergence of
      antibiotic-resistant strains of H. pylori, the development of novel treatment
      modalities for antibiotic-resistant H. pylori infection is a key priority. Blue
      light-emitting diodes (LED) may represent a unique option owing to their
      antimicrobial effect. In this study, we aimed to evaluate the anti-proliferative
      effect of blue LED against antibiotic-resistant H. pylori. METHODS: Ten
      antibiotic-resistant strains and one sensitive H. pylori strain were used in this
      study. After irradiation by blue LED along time course, the viability of H.
      pylori was evaluated by enumerating colony forming units. Morphological changes
      in H. pylori were observed using a scanning electron microscope. Reductase
      activity was measured as an indicator of bacterial cellular activity. Total
      reactive oxygen species was monitored using fluorescence intensity and
      fluorescence microscope imaging. RESULTS: After irradiation by blue LED, the
      numbers of H. pylori in all the strains were significantly reduced compared with
      control group. The H. pylori exhibited a short rod-shaped morphology after
      irradiation; no such change was observed in H. pylori not exposed to blue LED. Re
      irradiation of surviving strain after the initial irradiation also exhibited the
      same anti-proliferation effect. After blue LED irradiation, bacterial cellular
      activity was lower, and total reactive oxygen species production was
      significantly higher in blue LED group, compared with that in control.
      CONCLUSIONS: Blue LED could be a new treatment to eradicate infection with
      antibiotic-resistant H. pylori.

PMID- 29218794
TI  - Examining the potential for porcine-derived islet cells to harbour viral
      pathogens.
AB  - With an onus on safety in the potential use of porcine islet cells as a treatment
      for diabetes, the use of animals lacking exogenous pathogens is clearly important
      and multilevel screening strategies have been presented on testing animals and
      the product. In this study, we wished to investigate whether islet cells indeed
      harboured the same viral pathogens of concern in the source animal. PMBC and
      islet cells from both adult and neonatal source animals were directly compared
      and tested for PCMV, PLHV, PCV2, PPV and HEV using both molecular and serological
      assays. Adult PBMC were found positive for all viruses with the exception of PCV2
      and HEV. Neonatal PBMC were only found positive for PCMV and HEV. All animals
      were found negative for HEV antibodies. Interestingly, islet cells were negative
      for all viruses tested regardless of status in the animal-derived PBMC. Given
      that other laboratories have demonstrated the lack of virus detection during the
      culture of islets, this study also demonstrates that the hygiene status of the
      herd may not reflect the status of the product. This is important for
      establishing guidelines for any risk evaluation and mitigation process utilised
      during product manufacture.

PMID- 29218796
TI  - Impact of neoadjuvant chemotherapy on the immune microenvironment in advanced
      epithelial ovarian cancer: Prognostic and therapeutic implications.
AB  - Over the last decade, increasing evidence highlights the role of the host immune
      system in the control of tumor growth and the prognostic implications of tumor
      infiltrating lymphocytes (TILs) in ovarian cancer. Most data support a better
      prognosis with accumulation of CD3+ and CD8 + TILs and a poor outcome associated
      with increased regulatory T cells. However, only a small number of studies have
      focused on the effect of neoadjuvant chemotherapy (NACT) on the tumor immune
      microenvironment. This review will provide an update on the prognostic value of
      TIL subpopulations at diagnosis and a comprehensive overview of the recent
      studies evaluating the impact of neoadjuvant chemotherapy on TILs and their
      relationship to clinical outcome in advanced ovarian cancer. This information
      could help in future investigations of immunotherapy as maintenance following
      primary treatment.

PMID- 29218795
TI  - Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof
      of Concept Study in Experimental Non-Small Cell Lung Carcinoma.
AB  - Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common
      treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular
      normalization following bevacizumab administration may transiently enhance drug
      delivery, suggesting improved efficacy with sequential administration. To
      investigate optimal scheduling, we conducted a study in NSCLC-bearing mice.
      First, experiments demonstrated improved efficacy when using sequential vs.
      concomitant scheduling of bevacizumab and chemotherapy. Combining this data with
      a mathematical model of tumor growth under therapy accounting for the
      normalization effect, we predicted an optimal delay of 2.8 days between
      bevacizumab and chemotherapy. This prediction was confirmed experimentally, with
      reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged
      survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a
      similar increase in efficacy, thus emphasizing the utility of modeling support to
      identify optimal scheduling. The model could also be a useful tool in the clinic
      to personally tailor regimen sequences.

PMID- 29218797
TI  - Lymphoepithelioma-like carcinoma of the uterine cervix: Cytomorphologic features
      and diagnostic pitfalls by liquid-based cytology.
AB  - Lymphoepithelioma-like carcinoma (LELC) is a rare variant of cervical squamous
      cell carcinoma with unclear HPV and EBV association. Due to the accompanying and
      often obscuring lymphocytic inflammation, malignant cells may be difficult to
      recognize on cytologic samples and can mimic several more common benign and
      atypical cervical lesions. In this case report, we describe the cytomorphologic
      findings of LELC by liquid-based cytology in a 59-year-old Caucasian woman who
      was positive for high risk HPV but had no visible cervical lesions. We also
      discuss the differential diagnosis, diagnostic pitfalls, and practical
      considerations for diagnosis.

PMID- 29218798
TI  - High Risk Clinical Features for Acute Aortic Dissection: A Case-Control Study.
AB  - BACKGROUND: Acute aortic dissection (AAD) is a rare condition with a high
      mortality that is often missed. The objective of our study was to assess the
      diagnostic accuracy of clinical and laboratory findings for AAD, in confirmed
      cases of AAD and in a low-risk control group. METHODS: This was a historical
      matched case-control study: participants were adults > 18 years old presenting to
      two tertiary care emergency departments (EDs) or one regional cardiac referral
      center. Cases were patients with new ED or in-hospital diagnosis of nontraumatic
      AAD confirmed by computed tomography or echocardiography. Controls were patients
      with a triage diagnosis of truncal pain (<14 days) and an absence of a clear
      diagnosis on basic investigation. Cases and controls were matched in a 1:4 ratio
      by sex and age. A sample size of 165 cases and 660 controls was calculated based
      on 80% power and confidence interval of 95% to detect an odds ratio of greater
      than 2. RESULTS: Data were collected from 2002 to 2014 yielding 194 cases of AAD
      and 776 controls (mean +/- SD age = 65 +/- 14.1 years; 66.7% male). Absence of
      abrupt-onset pain (sensitivity = 95.9%, negative likelihood ratio = 0.07 [0.03
      0.14]) can help rule out AAD. Presence of tearing/ripping pain (specificity =
      99.7%, positive likelihood ratio [LR+] = 42.1 [9.9-177.5]), aortic aneurysm
      (specificity = 97.8%, LR+ = 6.35 [3.54-11.42]), hypotension (specificity = 98.7%,
      LR+ = 17.2 [8.8-33.6]), pulse deficit (specificity = 99.3, LR+ = 31.1 [11.2
      86.6]), neurologic deficits (specificity = 96.9%, LR+ = 5.26 [2.9-9.3]), and a
      new murmur (specificity = 97.8%, LR+ = 9.4 [5.5-16.2]) can help rule in the
      diagnosis of AAD. CONCLUSIONS: Patients with one or more high-risk feature should
      be considered high risk, whereas patients with no high-risk and multiple low-risk
      features are at low risk for AAD.

PMID- 29218800
TI  - Ultrastretchable Kirigami Bioprobes.
AB  - An ultrastretchable film device is developed that can follow the shape of
      spherical and large deformable biological samples such as heart and brain
      tissues. Although the film is composed of biocompatible parylene for the device
      substrate and metal layers of platinum (Pt)/titanium (Ti), which are
      unstretchable materials, the film shows a high stretchability by patterning slits
      as a "Kirigami" design. A Pt/Ti-microelectrode array embedded in 11 um thick
      parylene film with 5 * 91 slits exhibits a film strain of ~250% at 9 mN strain
      force (0.08 MPa in stress) with a Young's modulus of 23 kPa, while the 3 * 91
      slit film shows a Young's modulus of 3.6 kPa. The maximum strains of these
      devices are ~470% and ~840%, respectively. It is demonstrated that the Kirigami
      based microelectrode device can simultaneously record in vivo electrocorticogram
      signals from the visual and barrel cortices of a mouse by stretching the film and
      tuning the electrode gap. Moreover, wrapping the Kirigami device around a beating
      mouse's heart, which shows large and rapid changes in the volume and the surface
      area, can record the in vivo epicardial electrocardiogram signals. Such a small
      Young's modulus for a stretchable device reduces the device's strain-force,
      minimizing the device-induced stress to soft biological tissues.

PMID- 29218799
TI  - Structural factors associated with methamphetamine smoking among female sex
      workers in Tijuana, Mexico.
AB  - INTRODUCTION AND AIMS: Smoking methamphetamine is associated with increased risk
      of HIV among female sex workers (FSW). The structural context of substance use is
      an important shaper of individual behaviour; however, structural determinants of
      methamphetamine use among FSWs are largely unknown. We identified individual,
      structural and neighbourhood factors associated with smoking methamphetamine
      among FSWs in the border city of Tijuana, Baja California, Mexico. DESIGN AND
      METHODS: A prospective cohort of 301 FSWs sampled from indoor and outdoor sex
      work venues throughout Tijuana participated in quantitative surveys on behaviours
      and mapping of home and work neighbourhoods across three visits. Multinomial
      logistic regression using generalised estimating equations identified individual,
      structural and neighbourhood variables associated with smoking methamphetamine.
      RESULTS: Methamphetamine use, particularly smoking, was highly prevalent among
      FSWs. Over half (61%) of FSWs had ever used methamphetamine in their lifetime and
      at baseline, 38% currently smoked methamphetamine. Smoking methamphetamine daily
      was associated with living in the red light district [adjusted odds ratio (AOR) =
      2.72, 95% confidence interval (CI) = 1.23-6.02] and with perceived homelessness,
      but only among women in a good financial situation (AOR = 4.08, 95% CI = 1.58
      10.50). Smoking methamphetamine less than daily was associated with older age
      (AOR = 1.06, 95% CI = 1.02-1.10). DISCUSSION AND CONCLUSIONS: Our findings point
      to the important dynamic between the residential environment and more severe
      methamphetamine use. FSWs may prioritise the purchase of methamphetamine over
      stable housing if they have the financial means. Given the high prevalence of
      smoking methamphetamine among FSWs in Tijuana, drug treatment options, especially
      for women living in the red light district, are needed.

PMID- 29218801
TI  - Frontiers in alley cropping: Transformative solutions for temperate agriculture.
AB  - Annual row crops dominate agriculture around the world and have considerable
      negative environmental impacts, including significant greenhouse gas emissions.
      Transformative land-use solutions are necessary to mitigate climate change and
      restore critical ecosystem services. Alley cropping (AC)-the integration of trees
      with crops-is an agroforestry practice that has been studied as a transformative,
      multifunctional land-use solution. In the temperate zone, AC has strong potential
      for climate change mitigation through direct emissions reductions and increases
      in land-use efficiency via overyielding compared to trees and crops grown
      separately. In addition, AC provides climate change adaptation potential and
      ecological benefits by buffering alley crops to weather extremes, diversifying
      income to hedge financial risk, increasing biodiversity, reducing soil erosion,
      and improving nutrient- and water-use efficiency. The scope of temperate AC
      research and application has been largely limited to simple systems that combine
      one timber tree species with an annual grain. We propose two frontiers in
      temperate AC that expand this scope and could transform its climate-related
      benefits: (i) diversification via woody polyculture and (ii) expanded use of tree
      crops for food and fodder. While AC is ready now for implementation on marginal
      lands, we discuss key considerations that could enhance the scalability of the
      two proposed frontiers and catalyze widespread adoption.

PMID- 29218802
TI  - Re: Perinatal and maternal morbidity and mortality among term singletons
      following midcavity operative vaginal delivery versus caesarean delivery.

PMID- 29218803
TI  - Community pharmacist-led clinical services: physician's understanding,
      perceptions and readiness to collaborate in a Midwestern state in the United
      States.
AB  - OBJECTIVES: Many pharmacists are actively enhancing their role in the delivery of
      health care by offering a variety of pharmacist-led clinical services. The
      delivery of these services within community pharmacies can contribute to
      overcoming the cost and accessibility challenges currently facing U.S. health
      care, especially when pharmacist-physician collaborative efforts are utilized.
      The study purpose was to identify general and family practice physicians'
      awareness of pharmacists' delivery of clinical services, uncover their perceived
      barriers to collaboration with community pharmacists, and collect their input on
      how to overcome such barriers in order to better understand how pharmacist-led
      clinical services can be integrated, improved and more widely utilized as a
      healthcare delivery mechanism. METHODS: Semi-structured interviews were performed
      at the physicians' place of practice to assess (1) family practice and internal
      medicine physicians' knowledge of pharmacists' education, clinical training, and
      role in the healthcare team; (2) their perceptions and barriers towards
      pharmacist-delivered clinical services and physician-pharmacist collaboration;
      and (3) their recommendations to improve physician-pharmacist collaboration. The
      data were analysed qualitatively to identify and categorize themes. KEY FINDINGS:
      Thirteen physicians were interviewed. While nearly all physicians were aware of
      pharmacists' level of education, most were not aware of the level of clinical
      training pharmacists receive. Only half of the physicians were able to provide a
      definition or example of collaborative practice agreements, although most
      recognized value and benefit when the definition and examples were provided to
      them. The commonly perceived barriers for collaboration were concern over loss of
      communication, hesitancy to relinquish control and lack of confidence in
      pharmacists' clinical judgement. CONCLUSION: The study results emphasize the need
      to develop strategies to improve collaborative relationships between physicians
      and pharmacists. To encourage collaboration, pharmacists must take a proactive
      approach to increasing awareness of their clinical knowledge and training, the
      benefits and value of collaborative practice and the opportunities for it.

PMID- 29218805
TI  - 2017 Japanese Neuropathology Prizes.

PMID- 29218804
TI  - Impact of diabetes on free flap surgery of the head and neck: A NSQIP analysis.
AB  - OBJECTIVE: Diabetes is associated with microvascular pathology and may predispose
      patients undergoing microvascular surgery to complications. This study assesses
      diabetes as a risk factor for complications following free flap surgery of the
      head and neck. PATIENTS AND METHODS: In this retrospective cohort study, data on
      free flap surgeries of the head and neck between 2005 and 2014 was collected from
      the National Surgical Quality Improvement Program (NSQIP) database. A propensity
      matching algorithm (PSM) was used to equilibrate distribution of numerous
      covariates between the diabetic and nondiabetic cohorts. A sub-analysis was
      performed to examine the impact of insulin-dependency. RESULTS: The initial
      dataset contained 2187 free flaps of the head and neck. After implementing PSM, a
      new population was created containing 506 total cases with 253 DM patients. The
      majority of cases were male and white. The matched cohort did not contain any
      demographics or comorbidities associated with DM. Complications significantly
      elevated in the DM group were severe bleeding (P = .046), postoperative
      ventilation greater than 48 hours (P < .001), and pneumonia (P < .048). In
      patients with insulin-dependent diabetes, reintubation (P = .005), cardiac arrest
      (P = .010), severe bleeding (P = .006), overall surgical complications (P =
      .015), and overall complications (P = .005) were significantly increased.
      CONCLUSION: This study examines the impact of diabetes on postoperative
      complications following free flap reconstruction of the head and neck. Propensity
      score matching was utilized. Analysis of the PSM cohort suggests that diabetic
      patients have elevated rates of postoperative pulmonary complications.
      Additionally, patients with insulin-dependent diabetes have significantly
      elevated rates of medical and surgical complications.

PMID- 29218807
TI  - Observational study on the occurrence of surgical glove perforation and
      associated risk factors in large animal surgery.
AB  - OBJECTIVE: To determine the incidence of and associated risk factors for glove
      perforation in large animal surgery. STUDY DESIGN: Prospective observational
      cohort study. SAMPLE POPULATION: Surgical gloves (n = 917) worn during 103 large
      animal surgical procedures. METHODS: Gloves worn by personnel involved in sterile
      preparation and surgical procedures were tested for perforation by 2 previously
      validated methods, water leak test (WLT) and electroconductivity testing (ECT).
      The association between surgical and glove-related variables and glove
      perforation was assessed by using a multivariable mixed-effect logistic
      regression model. RESULTS: At least 1 glove perforation was detected in 66% of
      surgical procedures, and 17.9% (164/917) of gloves tested were identified as
      perforated. All perforations were detected by ECT, whereas only 110/178 (61.8%)
      were detected by WLT. All perforations detected by WLT were also detected by ECT.
      The risk of glove perforation increased with duration of wear (>60 minutes odds
      ratio [OR] 2.3, 95% CI 1.4-3.7; P < .001) and with invasiveness of procedures (OR
      7.9, 95% CI 3.2-19.5; P < .001). Primary surgeons were at higher risk for glove
      perforation than first (OR 1.7, 95% CI 1.1-2.5; P = .008) and second (OR 3.4, 95%
      CI 2-6.7; P < .001) assistants. Only 25% of glove perforations were detected
      intraoperatively by the wearer. CONCLUSION: Incidence of glove perforation is
      similar in large animal, human, and small animal surgery and is influenced by
      duration of wear, invasiveness of the surgery, and role of the wearer. ECT is
      more sensitive than WLT for detection of glove perforation.

PMID- 29218808
TI  - The feasibility and acceptability of a physical activity intervention for older
      people with chronic musculoskeletal pain: The iPOPP pilot trial protocol.
AB  - INTRODUCTION: This pilot trial will inform the design and methods of a future
      full-scale randomized controlled trial (RCT) and examine the feasibility,
      acceptability and fidelity of the Increasing Physical activity in Older People
      with chronic Pain (iPOPP) intervention, a healthcare assistant (HCA)-supported
      intervention to promote walking in older adults with chronic musculoskeletal pain
      in a primary care setting. METHODS AND ANALYSIS: The iPOPP study is an
      individually randomized, multicentre, three-parallel-arm pilot RCT. A total of
      150 participants aged >=65 years with chronic pain in one or more index sites
      will be recruited and randomized using random permuted blocks, stratified by
      general practice, to: (i) usual care plus written information; (ii) pedometer
      plus usual care and written information; or (iii) the iPOPP intervention. A
      theoretically informed mixed-methods approach will be employed using semi
      structured interviews, audio recordings of the HCA consultations, self-reported
      questionnaires, case report forms and objective physical activity data collection
      (accelerometry). Follow-up will be conducted 12 weeks post-randomization.
      Collection of the quantitative data and statistical analysis will be performed
      blinded to treatment allocation, and analysis will be exploratory to inform the
      design and methods of a future RCT. Analysis of the HCA consultation recordings
      will focus on the use of a checklist to determine the fidelity of the iPOPP
      intervention delivery, and the interview data will be analysed using a constant
      comparison approach in order to generate conceptual themes focused around the
      acceptability and feasibility of the trial, and then mapped to the Theoretical
      Domains Framework to understand barriers and facilitators to behaviour change. A
      triangulation protocol will be used to integrate quantitative and qualitative
      data and findings.

PMID- 29218809
TI  - Reversing Conventional Reactivity of Mixed Oxo/Alkyl Rare-Earth Complexes: Non
      Redox Oxygen Atom Transfer.
AB  - The preferential substitution of oxo ligands over alkyl ones of rare-earth
      complexes is commonly considered as "impossible" due to the high oxophilicity of
      metal centers. Now, it has been shown that simply assembling mixed methyl/oxo
      rare-earth complexes to a rigid trinuclear cluster framework cannot only enhance
      the activity of the Ln-oxo bond, but also protect the highly reactive Ln-alkyl
      bond, thus providing a previously unrecognized opportunity to selectively
      manipulate the oxo ligand in the presence of numerous reactive functionalities.
      Such trimetallic cluster has proved to be a suitable platform for developing the
      unprecedented non-redox rare-earth-mediated oxygen atom transfer from ketones to
      CS2 and PhNCS. Controlled experiments and computational studies shed light on the
      driving force for these reactions, emphasizing the importance of the sterical
      accessibility and multimetallic effect of the cluster framework in promoting
      reversal of reactivity of rare-earth oxo complexes.

PMID- 29218810
TI  - A prospective, multi-center study assessing early loading with short implants in
      posterior regions. A 3-year post-loading follow-up study.
AB  - BACKGROUND: Few prospective studies about early loading of short implant have
      been available and very little evidence exists on the outcomes longer than 3
      years. PURPOSE: To assess clinical and radiographic outcomes of 6 mm-short
      implants placed in the posterior maxilla and mandible applying an early loading
      protocol. MATERIALS AND METHODS: Ninety-five short implants (6 mm-short, O 4 mm)
      were placed in 45 subjects at 3 study sites, 2 or 3 implants per subject, using a
      one-stage surgical procedure and loaded with a screw-retained splinted fixed
      prosthesis 6 weeks later. Follow-up took place at 6, 12, 24, and 36 months after
      loading. Marginal bone level changes, implant survival, clinical variables, and
      adverse events were assessed. RESULTS: The survival rate for all implants placed
      was 95.8%. From implant loading to 3 years follow-up, mean marginal bone level
      changes were minimal (0.07 +/- 0.49 mm) and the peri-implant soft tissue status
      was healthy. No major technical or biological complications occurred except for
      the 4 early implant losses. CONCLUSION: Three-year data indicates that the use of
      splinted 6 mm-short implants is a viable treatment in posterior regions with low
      marginal bone resorption. Early loading after 6 weeks should be taken cautiously
      in patients with known risk factors.

PMID- 29218811
TI  - Exploring the chemistry of complex samples by tentative identification and
      semiquantification: A food contact material case.
AB  - In fields such as food safety and environmental chemistry, ensuring safety is
      greatly challenged by large numbers of unknown substances occurring. Even with
      current state-of-the-art mass spectrometers, dealing with nonidentified
      substances is a very laborious process as it includes structure elucidation of a
      vast number of unknowns, of which only a fraction may be relevant. Here, we
      present an exploration and prioritization approach based on high-resolution mass
      spectrometry. The method uses algorithm-based precursor/product-ion correlations
      on quadrupole time-of-flight tandem mass spectrometry data to retrieve the most
      likely chemical match from a structure database. In addition, time-of-flight-only
      data are used to estimate analyte concentration via semiquantification. The
      method is demonstrated in recycled paper food contact material. Here, 585
      chromatographic peaks were discovered, of which 117 were unique to the sample and
      could be tentatively elucidated via accurate mass, isotopic pattern, and
      precursor/product-ion correlations. Nearly 85% of these 117 peaks were matched
      with database entries, which provided varying certainty of information about the
      analyte structure. Semiquantitative concentration ranges of investigated
      compounds were between 0.7 and 1600 MUg dm-2 . With these data, a subgroup of
      chemicals was risk-categorized and prioritized by using the most likely candidate
      structure(s) obtained. Prioritization based on expected health impact was
      possible by using the tentatively assigned data. Overall, the described method
      not only is a valuable chemical exploration tool for nonidentified substances but
      may also be used as a preliminary prioritization tool for substances expected to
      have the highest health impact, for example, in food contact materials.

PMID- 29218812
TI  - Gold-Catalyzed Divergent Ring-Closing Modes of Indole-Tethered Amino Allenynes.
AB  - Indole-tethered amino allenynes were chemodivergently cyclized for the controlled
      preparation of fused polycyclic indoles using gold catalysis. Double cyclization
      of terminal allenynes afforded hexacyclic 15 H-indolo[1,2,3-de]quinolino[3,2,1
      ij]quinoxalines, in which allenynes bearing a substituted alkyne at the terminal
      end generated 12,13-dihydro-7 H-indolo[3,2-c]acridines, which are 5-membered
      cyclized adducts. Density functional theory calculations were performed to shed
      light on this difference in reactivity.

PMID- 29218813
TI  - Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with
      cirrhosis in patients with HBV infection: Systematic review with meta-analysis.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide health issue and is
      well known for being the main cause of developing secondary liver complications
      such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409
      polymorphism has been investigated conclusively with occurrence risk of steatosis
      and cirrhosis. Therefore, performing a meta-analysis of the available studies
      with the aim of clarifying the association between rs738409 and occurrence risk
      of steatosis and cirrhosis among HBV-infected patients would be helpful. METHODS:
      Chronic HBV infection was defined as the persistence of HBsAg for more than 6
      months. To gather sufficient data for this meta-analysis, reliable databases were
      conclusively searched using appropriate keywords. Only studies that satisfied the
      inclusion criteria were enrolled in the present study. RESULTS: This meta
      analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to
      evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies
      with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The
      association of rs738409 with each complication was investigated. The rs738409 was
      found to be associated with steatosis in recessive [p = 4.57 * 10-6 , odds ratio
      (OR) = 2.85], dominant (p = 4.35 * 10-6 , OR = 1.84), co-dominant (p = 6.18 * 10
      8 ; OR = 3.74) and allelic (p = 9.79 * 10-9 ; OR = 1.78) models. No association
      was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR =
      1.00), dominant (p = 0.30, OR = 0.92), co-dominant (p = 0.74; OR = 0.96) and
      allelic (p = 0.45; OR = 0.96) models. CONCLUSIONS: Although the PNPLA3 rs738409 G
      allele has been associated with the risk of steatosis in CHB patients, no
      association between this polymorphism and the risk of cirrhosis was seen.

PMID- 29218814
TI  - Knowledge, compliance with good clinical practices and barriers to effective
      control of postoperative pain among nurses from hospitals with and without a
      "Hospital without Pain" certificate.
AB  - AIMS AND OBJECTIVES: (i) To compare knowledge and compliance with good clinical
      practices regarding control of postoperative pain among nurses employed at
      hospitals with and without a "Hospital without Pain" certificate, (ii) to
      identify the determinants of nurses' knowledge and (iii) to define barriers to
      effective control of postoperative pain. BACKGROUND: Only a slight improvement in
      postoperative pain control has been observed recently, if any. Implementation of
      good clinical practices in the control of postoperative pain requires involvement
      of nurses. DESIGN: A cross-sectional study. METHODS: The study included 257
      nurses from hospitals with a "Hospital without Pain" certificate and 243 nurses
      from noncertified hospitals, with mean job seniority of 17.6 +/- 9.6 years. All
      respondents answered 26 questions regarding postoperative pain control-related
      issues. Based on the answers, overall scores were calculated for (i) nurses'
      knowledge, (ii) compliance with good clinical practices and (iii) barriers to
      effective control of postoperative pain. RESULTS: Nurses from the certified
      hospitals presented with significantly higher levels of knowledge and compliance
      with good clinical practices and identified significantly more barriers to
      effective control of postoperative pain. Apart from certification of a hospital,
      better knowledge of postoperative pain control was determined by higher
      education, participation in postgraduate training programmes and other relevant
      courses, self-education from medical journals, employment at paediatric ward or
      intensive care unit. The most commonly reported barriers to effective control of
      pain included too low doses of painkillers prescribed by physicians and inability
      to modify the protocol of pain treatment by the nurse. CONCLUSIONS: Control of
      postoperative pain can be improved by enrolling nurses in various forms of
      continuous training and by providing them with greater autonomy in administering
      painkillers to surgical patients. RELEVANCE TO CLINICAL PRACTICE: Better quality
      of care offered to patients with postoperative pain can be achieved by continuous
      education of nurses and physicians, and greater compliance with relevant good
      clinical practices.

PMID- 29218815
TI  - Prospective systemic risk analysis of the dispensing process in German community
      pharmacies.
AB  - BACKGROUND: Medicine dispensing represents an error-prone activity, carrying a
      considerable risk for patients. OBJECTIVE: To prospectively identify and
      prioritize potential failure modes in the medicine dispensing process as well as
      to develop corrective actions for patient safety improvement in German community
      pharmacies. METHOD: Failure mode and effects analysis was performed in 2
      community pharmacies in North Rhine-Westphalia, Germany, in October 2016. A 9
      member team was assembled, comprising of a leader and process experts who
      prospectively assessed the medicine dispensing process by brainstorming,
      quantified the attributed risks, proposed corrective actions, and reassessed the
      risks. RESULTS: The analysis identified 39 failure modes, out of which the
      highest criticality scores were assigned to inadequate assessment of therapy
      appropriateness (Risk Priority Number 45), reluctance to deviate from rebate
      contracts (36), and dispensing the wrong medicine (30). The corrective actions
      proposed demonstrated a considerable potential for risk reduction in most failure
      modes, the most effective of which were introducing obligatory continuous
      education for pharmacists, organizing communication training, and implementing
      electronic prescribing. CONCLUSION: This analysis not only detected various
      potential safety issues concerning the dispensing in Germany but also strongly
      indicated that application of failure mode and effects analysis could be highly
      effective in prospective risk reduction in community pharmacies.

PMID- 29218816
TI  - Long-term adherence with psychiatric treatment among patients with psychogenic
      nonepileptic seizures.
AB  - We conducted a prospective cohort study, examining long-term adherence with
      psychiatric treatment among patients with psychogenic nonepileptic seizures
      (PNES). Subjects diagnosed with documented PNES were scheduled for 4 psychiatric
      visits. Survival analysis was performed, and covariates were assessed for
      association with time to nonadherence using Cox proportional hazard regression
      analysis. One hundred twenty-three subjects were recruited and followed for up to
      17 months. Eighty percent of subjects attended the first outpatient visit, 42%
      attended the second, 24% attended the third, and only 14% remained adherent
      through the fourth visit. Two covariates were associated with nonadherence: (1) a
      prior diagnosis of PNES (hazard ratio 1.57, P-value .046); (2) a lower score on
      the Brief Illness Perception Questionnaire (BIPQ), signifying lower concern about
      one's illness (hazard ratio 0.77 for every 10-point increment on the 80-point
      scale, P-value .008). Adherence with psychiatric treatment among patients with
      PNES is initially reasonably good but worsens rapidly over visits 2-4. Risk
      factors for nonadherence include a history of a prior diagnosis of PNES, and a
      lower level of concern about the illness as assessed by a lower score on the
      BIPQ.

PMID- 29218817
TI  - Impact of a Shared Decision Making Intervention on Health Care Utilization: A
      Secondary Analysis of the Chest Pain Choice Multicenter Randomized Trial.
AB  - BACKGROUND: Patients at low risk for acute coronary syndrome are frequently
      admitted for observation and cardiac testing, resulting in substantial burden and
      cost to the patient and the health care system. OBJECTIVES: The purpose of this
      investigation was to measure the effect of the Chest Pain Choice (CPC) decision
      aid on overall health care utilization as well as utilization of specific
      services both during the index emergency department (ED) visit and in the
      subsequent 45 days. METHODS: This was a planned secondary analysis of data from a
      pragmatic multicenter randomized trial of shared decision making in adults
      presenting to the ED with chest pain who were being considered for observation
      unit admission for cardiac stress testing or coronary computed tomography
      angiography. The trial compared an intervention group engaged in shared decision
      making facilitated by the CPC decision aid to a control group receiving usual
      care. Hospital-level billing data were used to measure utilization for the index
      ED visit and during the following 45 days. Patients in both groups also were
      asked to keep a diary recording health care utilization over the same 45-day
      period. Outcomes assessed included length of time in the ED and observation, ED
      visits, office visits, hospitalizations, testing, imaging, and procedures.
      RESULTS: Of the 898 patients included in the original trial, we were able to
      contact 834 (92.9%) patients for 45-day health care diary review. There was no
      difference in patient-reported health care utilization between the study arms.
      Hospital-level billing data were obtained for all 898 (100%) patients. During the
      initial ED visit the length of stay (LOS) was similar, and there was no
      difference in the frequency of observation unit admission between study arms.
      However, the mean observation unit LOS was 95 minutes (95% confidence interval
      [CI] = 40.8-149.8) shorter in the CPC arm and the mean number of tests was lower
      in the CPC arm (decrease in 19.4 imaging studies per 100 patients, 95% CI = 15.5
      23.3). When evaluating the entire encounter and follow-up period, the
      intervention arm underwent fewer tests (decrease in 125.6 tests per 100 patients,
      95% CI = 29.3-221.6). More specifically, there were fewer advanced cardiac
      imaging tests completed (25.8 fewer per 100 patients, 95% CI = 3.74-47.9) in the
      intervention arm. CONCLUSIONS: Shared decision making in low-risk chest pain can
      lead to decreased diagnostic testing without worsening outcomes measured over 45
      days.

PMID- 29218818
TI  - Loss of fundus view as an indication for secondary enucleation in retinoblastoma.
AB  - In this retrospective study, we evaluated loss of fundus view as an indication
      for secondary enucleation and associated histopathologic findings. Of 64
      secondarily enucleated eyes, 24 were enucleated for loss of fundus view. Average
      time from loss of fundus view to enucleation was 4.7 months. Of these eyes, 22
      had viable tumor cells on histopathology, but none had high-risk features. Loss
      of fundus view was a common indication for secondary enucleation after
      chemoreduction. Given the high prevalence of viable histopathologic tumor cells,
      enucleation for loss of fundus view should not be significantly delayed to
      decrease risk of high-risk tumor progression.

PMID- 29218819
TI  - A conceptual model of the risk of elder abuse posed by incontinence and care
      dependence.
AB  - AIMS AND OBJECTIVES: To describe and critically analyse the thinking that led to
      the concept of an association between incontinence, care dependence and elder
      abuse. BACKGROUND: Coercive or abusive continence care practices include
      chastising a person for their incontinence and overriding their attempts to
      resist continence care. Neglect in continence care is characterised by
      withholding or delaying responding to requests for help to maintain continence or
      to manage incontinence, and restricting a person's access to toileting
      assistance, incontinence aids or hygiene care. METHODS: Contemporary biomedical
      understandings about incontinence and influencing concepts from the fields of
      sociology, psychology and nursing were analysed to inform the design of a
      conceptual model that elucidates possible associations between incontinence, care
      dependence and elder abuse. RESULTS: Ideas generated from an analysis of the
      concepts led to the development of a model termed the "Model of Attributes to
      Abuse of Dependent Elders in Continence Care" (MADE-CC). The MADE-CC theorises
      factors that cause and contribute to abuse in continence care. Carer factors
      include physical and emotional exhaustion, frustration related to the inability
      to control or predict incontinence, resentment associated with constraints
      imposed by care dependence, disgust associated with physical contact with
      urine/faeces, limited knowledge and skills about incontinence and ethical
      conflicts concerning care. Care recipient factors include frequent and severe
      incontinence, cognitive impairment and a history of physical or psychological
      trauma. Social factors that are theorised include the stigmatised nature of
      incontinence, social taboos and cultural norms and the private nature of
      continence care. CONCLUSIONS: The MADE-CC illuminates the potential risk of elder
      abuse posed by incontinence and care dependence. It should be used to improve
      ethical care of older people and stimulate debate about everyday ethics in the
      care of older people who are care dependent and to optimise their participation
      in decisions about their health and well-being. IMPLICATIONS FOR PRACTICE: Nurses
      and carers should be aware of the multiple interrelated factors that contribute
      to the risk of elder abuse in the caregiving encounter, including the role of
      emotions.

PMID- 29218820
TI  - Frequency of going outdoors and health-related quality of life among older
      adults: Examining the moderating role of living alone and employment status.
AB  - AIM: Going outdoors more frequently is beneficial for maintaining and improving
      health-related quality of life (HRQOL) among older adults. However, individual
      differences can alter the effects of going outdoors. The present study aimed to
      examine whether relationships between going outdoors and HRQOL were moderated by
      living alone and employment status. METHODS: The present study was a secondary
      analysis of 14-month prospective data (n = 613). Variables used in this study
      were baseline data on the frequency of going outdoors, HRQOL (physical and mental
      component summary scores assessed using the Japanese version of the Medical
      Outcomes study Short Form 8-Item Health Survey), living alone, employment status,
      potential confounders (sex, age, educational level and instrumental activities of
      daily living) and follow-up data on HRQOL. RESULTS: Mixed models showed that the
      interaction term of going outdoors and currently living alone on both the
      physical and mental component summary and that of going outdoors and current
      employment status on the mental component were significant. Stratified analyses
      showed that going outdoors more frequently predicted the physical and mental
      component summary among those who lived with others, and the mental component
      summary among those who were unemployed. CONCLUSIONS: These results show that the
      influence of going outdoors on HRQOL was moderated by living alone and employment
      status. Going outdoors more frequently might be important for the maintenance of
      HRQOL, especially among unemployed older adults living with others. Geriatr
      Gerontol Int 2018; 18: 640-647.

PMID- 29218821
TI  - Activity-dependent control of NMDA receptor subunit composition at hippocampal
      mossy fibre synapses.
AB  - KEY POINTS: CA3 pyramidal cells display input-specific differences in the subunit
      composition of synaptic NMDA receptors (NMDARs). Although at low density, GluN2B
      contributes significantly to NMDAR-mediated EPSCs at mossy fibre synapses. Long
      term potentiation (LTP) of NMDARs triggers a modification in the subunit
      composition of synaptic NMDARs by insertion of GluN2B. GluN2B subunits are
      essential for the expression of LTP of NMDARs at mossy fibre synapses. ABSTRACT:
      Single neurons express NMDA receptors (NMDARs) with distinct subunit composition
      and biophysical properties that can be segregated in an input-specific manner.
      The dynamic control of the heterogeneous distribution of synaptic NMDARs is
      crucial to control input-dependent synaptic integration and plasticity. In
      hippocampal CA3 pyramidal cells from mice of both sexes, we found that mossy
      fibre (MF) synapses display a markedly lower proportion of GluN2B-containing
      NMDARs than associative/commissural synapses. The mechanism involved in such
      heterogeneous distribution of GluN2B subunits is not known. Here we show that
      long-term potentiation (LTP) of NMDARs, which is selectively expressed at MF-CA3
      pyramidal cell synapses, triggers a modification in the subunit composition of
      synaptic NMDARs by insertion of GluN2B. This activity-dependent recruitment of
      GluN2B at mature MF-CA3 pyramidal cell synapses contrasts with the removal of
      GluN2B subunits at other glutamatergic synapses during development and in
      response to activity. Furthermore, although expressed at low levels, GluN2B is
      necessary for the expression of LTP of NMDARs at MF-CA3 pyramidal cell synapses.
      Altogether, we reveal a previously unknown activity-dependent regulation and
      function of GluN2B subunits that may contribute to the heterogeneous plasticity
      induction rules in CA3 pyramidal cells.

PMID- 29218822
TI  - European Academy of Neurology and European Stroke Organization consensus
      statement and practical guidance for pre-hospital management of stroke.
AB  - BACKGROUND AND PURPOSE: The reduction of delay between onset and hospital arrival
      and adequate pre-hospital care of persons with acute stroke are important for
      improving the chances of a favourable outcome. The objective is to recommend
      evidence-based practices for the management of patients with suspected stroke in
      the pre-hospital setting. METHODS: The GRADE (Grading of Recommendations
      Assessment, Development and Evaluation) methodology was used to define the key
      clinical questions. An expert panel then reviewed the literature, established the
      quality of the evidence, and made recommendations. RESULTS: Despite very low
      quality of evidence educational campaigns to increase the awareness of
      immediately calling emergency medical services are strongly recommended. Moderate
      quality evidence was found to support strong recommendations for the training of
      emergency medical personnel in recognizing the symptoms of a stroke and in
      implementation of a pre-hospital 'code stroke' including highest priority
      dispatch, pre-hospital notification and rapid transfer to the closest 'stroke
      ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke
      scale to predict large vessel occlusion. Despite the very low quality of
      evidence, restoring normoxia in patients with hypoxia is recommended, and blood
      pressure lowering drugs and treating hyperglycaemia with insulin should be
      avoided. There is insufficient evidence to recommend the routine use of mobile
      stroke units delivering intravenous thrombolysis at the scene. Because only
      feasibility studies have been reported, no recommendations can be provided for
      pre-hospital telemedicine during ambulance transport. CONCLUSIONS: These
      guidelines inform on the contemporary approach to patients with suspected stroke
      in the pre-hospital setting. Further studies, preferably randomized controlled
      trials, are required to examine the impact of particular interventions on quality
      parameters and outcome.

PMID- 29218823
TI  - Perspectives of cannabis use in the life experience of men with schizophrenia.
AB  - Substance use amongst people with schizophrenia is well-established: up to 50%
      report using illicit substances. The occurrence of both conditions can also
      induce people to disengage from mental health services. The research question
      sought to understand, from the perspective of both service users and clinicians,
      cannabis use within the experience of people with schizophrenia. The transcripts
      of the seven participants and the two focus groups were analysed using
      interpretative phenomenological analysis. Service Users and Clinicians were
      recruited from Assertive outreach community-based teams. seven male service users
      who described their ethnic identity as 'black', diagnosed with schizophrenia and
      a history of treatment disengagement and 12 clinicians who worked with this
      client group. The two component study involved semi-structured interviews with
      the Service Users and two focus groups with the Clinicians. Service Users
      perceived cannabis use as a means by which they could 'reestablish their
      identity' that had been damaged and the social consequences of diagnosis.
      Clinicians similarly perceived drugs, cannabis in particular, as a significant
      part of the service users' life. This study provides greater depth to
      understanding cannabis use within the experience of people with a diagnosis of
      schizophrenia.

PMID- 29218824
TI  - Solar Hydrogen Generation from Lignocellulose.
AB  - Photocatalytic reforming of lignocellulosic biomass is an emerging approach to
      produce renewable H2 . This process combines photo-oxidation of aqueous biomass
      with photocatalytic hydrogen evolution at ambient temperature and pressure.
      Biomass conversion is less energy demanding than water splitting and generates
      high-purity H2 without O2 production. Direct photoreforming of raw, unprocessed
      biomass has the potential to provide affordable and clean energy from locally
      sourced materials and waste.

PMID- 29218825
TI  - In vivo evidence supporting a metastasis suppressor role for Stard13 (Dlc2) in
      ErbB2 (Neu) oncogene induced mouse mammary tumors.
AB  - Overexpression of dominant oncogenes and the loss of tumor suppressor genes are
      basic genetic events in the acquisition of the malignant phenotype. The erb-b2
      receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of
      human breast cancers. The StAR related lipid transfer domain containing 13 gene
      (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome
      band 13q12.3 and is frequently downregulated in human cancers, including 72% of
      breast cancers. It encodes a RhoGAP protein with sterile alpha motif (SAM) and
      StAR-related lipid transfer (START) domains. The objective of this study was to
      determine if loss of Stard13 plays a role in mammary tumor progression using
      transgenic mice expressing the activated ErbB-2 (Neu) oncogene and Cre
      recombinase (NIC) in mammary epithelium under transcriptional control of the
      murine mammary tumor virus (MMTV) promoter (MMTV-NIC). These mice were crossed
      with a conditional Stard13 knockout mouse (floxed exon 3), resulting in
      simultaneous Neu expression and Stard13 deletion, specifically in the mammary
      epithelium. We found that loss of Stard13 did not alter tumor growth nor
      significantly modify overall survival and tumor free survival. However, there was
      an increase in the total number of lung metastases in the Stard13 heterozygous or
      homozygous mice compared with the parental MMTV-NIC strain. Altogether our
      results indicate that Stard13 acts as a metastasis suppressor rather than a tumor
      suppressor gene, in Neu oncogene induced mammary tumorigenesis.

PMID- 29218826
TI  - Poly(lactic acid) composites based on graphene oxide particles with antibacterial
      behavior enhanced by electrical stimulus and biocompatibility.
AB  - Poly(lactic acid) (PLA) is a biodegradable and biocompatible polyester widely
      used in biomedical applications. Unfortunately, this biomaterial suffers from
      some shortcomings related with the absence of both bioactivity and antibacterial
      capacity. In this work, composites of PLA with either graphene oxide (GO) or
      thermally reduced graphene oxide (TrGO) were prepared by melt mixing to overcome
      these limitations. PLA composites with both GO and TrGO inhibited the attachment
      and proliferation of Escherichia coli and Staphylococcus aureus bacteria
      depending on the kind and amount of filler. Noteworthy, it is shown that by
      applying an electrical stimulus to the percolated PLA/TrGO, the antibacterial
      behavior can be dramatically increased. MTT analysis showed that while all the
      PLA/GO composites were more cytocompatible to osteoblast-like cells (SaOS-2) than
      pure PLA, only low content of TrGO was able to increase this property. These
      tendencies were related with changes in the surface properties of the resulting
      polymer composites, such as polarity and roughness. In this way, the addition of
      GO and TrGO into a PLA matrix allows the development of multifunctional
      composites for potential applications in biomedicine. (c) 2017 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1051-1060, 2018.

PMID- 29218827
TI  - Computational study of estimating 3D trabecular bone microstructure for the
      volume of interest from CT scan data.
AB  - Inspired by the self-optimizing capabilities of bone, a new concept of bone
      microstructure reconstruction has been recently introduced by using 2D synthetic
      skeletal images. As a preliminary clinical study, this paper proposes a topology
      optimization-based method that can estimate 3D trabecular bone microstructure for
      the volume of interest (VOI) from 3D computed tomography (CT) scan data with
      enhanced computational efficiency and phenomenological accuracy. For this
      purpose, a localized finite element (FE) model is constructed by segmenting a
      target bone from CT scan data and determining the physiological local loads for
      the VOI. Then, topology optimization is conducted with multiresolution bone
      mineral density (BMD) deviation constraints to preserve the patient-specific
      spatial bone distribution obtained from the CT scan data. For the first time, to
      our knowledge, this study has demonstrated that 60-MUm resolution trabecular bone
      images can be reconstructed from 600-MUm resolution CT scan data (a 62-year-old
      woman with no metabolic bone disorder) for the 4 VOIs in the proximal femur. The
      reconstructed trabecular bone includes the characteristic trabecular patterns and
      has morphometric indices that are in good agreement with the anatomical data in
      the literature. As for computational efficiency, the localization for the VOI
      reduces the number of FEs by 99%, compared with that of the full FE model.
      Compared with the previous single-resolution BMD deviation constraint, the
      proposed multiresolution BMD deviation constraints enable at least 65% and 47%
      reductions in the number of iterations and computing time, respectively. These
      results demonstrate the clinical feasibility and potential of the proposed
      method.

PMID- 29218828
TI  - Monocytic myeloid-derived suppressor cells as prognostic factor in chronic
      myeloid leukaemia patients treated with dasatinib.
AB  - Myeloid suppressor cells are a heterogeneous group of myeloid cells that are
      increased in patients with chronic myeloid leukaemia (CML) inducing T cell
      tolerance. In this study, we found that therapy with tyrosine kinase inhibitors
      (TKI) decreased the percentage of granulocytic MDSC, but only patients treated
      with dasatinib showed a significant reduction in the monocytic subset (M-MDSC).
      Moreover, a positive correlation was observed between number of persistent M-MDSC
      and the value of major molecular response in dasatinib-treated patients. Serum
      and exosomes from patients with CML induced conversion of monocytes from healthy
      volunteers into immunosuppressive M-MDSC, suggesting a bidirectional crosstalk
      between CML cells and MDSC. Overall, we identified M-MDSC as prognostic factors
      in patients treated with dasatinib. It might be of interest to understand whether
      MDSC may be a candidate predictive markers of relapse risk following TKI
      discontinuation, suggesting their potential significance as practice of precision
      medicine.

PMID- 29218830
TI  - Effectiveness of vocabulary intervention for older children with (developmental)
      language disorder.
AB  - BACKGROUND: Children with developmental language disorder (DLD) frequently have
      difficulties with word learning and understanding vocabulary. For these children,
      this can significantly impact on social interactions, daily activities and
      academic progress. Although there is literature providing a rationale for
      targeting word learning in such children, there is little evidence for the
      effectiveness of specific interventions in this area for children with identified
      DLD. AIMS: To establish whether direct one-to-one intervention for children with
      DLD over 9 years of age leads to improved abilities to identify, comprehend,
      define, and use nouns and verbs targeted in intervention as compared with non
      targeted control items and whether or not the participants' rating of their own
      knowledge of the words changes with intervention. METHODS & PROCEDURES: Twenty
      five children and young people with language disorder (aged 9;4-16;1)
      participated in the study: 18 with DLD and seven with a language disorder
      associated with autism spectrum disorder (ASD). Two assessments of different
      levels were created: a higher ability (less frequent words) and a lower ability
      (more frequent words). Participants' speech and language therapists (SLTs)
      decided which level would be the most appropriate for each participant. Four
      tasks were carried out as part of the assessment and the scores were used to
      identify which words each participant worked on. Participants received one 30-min
      session per week one-to-one with their own SLT for 7 weeks, plus a 5-min revision
      session in between each main session. During each of the first five sessions,
      participants learned two new words; the two final sessions were spent revising
      the 10 words which had been targeted. OUTCOMES & RESULTS: Post-intervention
      assessment showed an increase in scores for both treated and control words.
      However, progress on treated words was significantly greater than on control
      words (d = 1.07), indicating effectiveness of intervention. The difference
      between progress on targeted and control words was found both for nouns (d =
      1.29) and verbs (d = 0.64), but the effect size was larger for nouns. Whether or
      not the participants had an associated ASD did not affect the results. The
      children's self-rating of their knowledge of the targeted words was also
      significantly higher than for control words post-intervention. CONCLUSIONS &
      IMPLICATIONS: The intervention delivered one-to-one by the participants' usual
      SLT was effective in teaching new vocabulary to older children with language
      disorders. This shows that older children with language disorders can make
      progress with direct one-to-one intervention focused on vocabulary.

PMID- 29218829
TI  - Intraclass correlation: Improved modeling approaches and applications for
      neuroimaging.
AB  - Intraclass correlation (ICC) is a reliability metric that gauges similarity when,
      for example, entities are measured under similar, or even the same, well
      controlled conditions, which in MRI applications include runs/sessions, twins,
      parent/child, scanners, sites, and so on. The popular definitions and
      interpretations of ICC are usually framed statistically under the conventional
      ANOVA platform. Here, we provide a comprehensive overview of ICC analysis in its
      prior usage in neuroimaging, and we show that the standard ANOVA framework is
      often limited, rigid, and inflexible in modeling capabilities. These intrinsic
      limitations motivate several improvements. Specifically, we start with the
      conventional ICC model under the ANOVA platform, and extend it along two
      dimensions: first, fixing the failure in ICC estimation when negative values
      occur under degenerative circumstance, and second, incorporating precision
      information of effect estimates into the ICC model. These endeavors lead to four
      modeling strategies: linear mixed-effects (LME), regularized mixed-effects (RME),
      multilevel mixed-effects (MME), and regularized multilevel mixed-effects (RMME).
      Compared to ANOVA, each of these four models directly provides estimates for
      fixed effects and their statistical significances, in addition to the ICC
      estimate. These new modeling approaches can also accommodate missing data and
      fixed effects for confounding variables. More importantly, we show that the MME
      and RMME approaches offer more accurate characterization and decomposition among
      the variance components, leading to more robust ICC computation. Based on these
      theoretical considerations and model performance comparisons with a real
      experimental dataset, we offer the following general-purpose recommendations.
      First, ICC estimation through MME or RMME is preferable when precision
      information (i.e., weights that more accurately allocate the variances in the
      data) is available for the effect estimate; when precision information is
      unavailable, ICC estimation through LME or the RME is the preferred option.
      Second, even though the absolute agreement version, ICC(2,1), is presently more
      popular in the field, the consistency version, ICC(3,1), is a practical and
      informative choice for whole-brain ICC analysis that achieves a well-balanced
      compromise when all potential fixed effects are accounted for. Third, approaches
      for clear, meaningful, and useful result reporting in ICC analysis are discussed.
      All models, ICC formulations, and related statistical testing methods have been
      implemented in an open source program 3dICC, which is publicly available as part
      of the AFNI suite. Even though our work here focuses on the whole-brain level,
      the modeling strategy and recommendations can be equivalently applied to other
      situations such as voxel, region, and network levels.

PMID- 29218831
TI  - Re: Ultrasound bladder wall thickness and detrusor overactivity: a multicentre
      test accuracy study: Is it fair to assess new imaging techniques against a poor
      gold standard?

PMID- 29218832
TI  - Necrotizing enterocolitis in the setting of milk allergy after pediatric living
      donor liver transplantation.
AB  - NEC is an idiopathic intestinal mucosal injury that may progress to transmural
      bowel necrosis without mesenteric ischemia. NEC usually affects 7- to 10-day-old
      neonates following enteral feeding. A 10-month-old girl with no history of
      laparotomy underwent LDLT for acute liver failure. After starting enteral feeding
      on postoperative day 5, she developed abdominal distention. Diffuse PVG and PI
      were detected by radiologic modalities. Exploratory laparotomy revealed patchy
      necrosis of the intestine without perforation. The microscopic findings of a
      resected specimen revealed transmural coagulative necrosis with multiple small
      thromboses compatible with neonatal NEC features, and eosinophil infiltration was
      also observed. Subsequently, after the resumption of enteral feeding with cow's
      milk, she developed severe diarrhea, the symptoms of which were eliminated after
      the administration of cow's milk was stopped. These clinical and pathological
      findings support the speculation that NEC might have been induced by a CMA. Food
      allergies, which can be induced by immunosuppressive agents, should be considered
      as a potential cause of NEC in the setting of pediatric liver transplantation.

PMID- 29218833
TI  - Consideration of children with intellectual disability as candidates for solid
      organ transplantation-A practice in evolution.
AB  - Children with intellectual disability were historically excluded from
      consideration as recipients of solid organ transplants. In light of an evolution
      in provider practices, this commentary will define intellectual disability and
      review the relevant provider attitudes and guidelines and known outcomes of solid
      organ transplant in this population.

PMID- 29218834
TI  - Comparative evaluation of simple indices using a single fasting blood sample to
      estimate beta cell function after islet transplantation.
AB  - Six single fasting blood sample-based indices-Secretory Unit of Islet Transplant
      Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model
      Assessment (HOMA)2-B%, C-peptide/glucose ratio (CP/G), C-peptide/glucose
      creatinine ratio (CP/GCr), and BETA-2 score-were compared against commonly used
      90-minute mixed meal tolerance test (MMTT) serum glucose and beta score to assess
      which of them best recognizes the state of acceptable blood glucose control
      without insulin supplementation after islet allotransplantation (ITx). We also
      tested whether the indices could identify the success of ITx based on the Igls
      classification of beta cell graft function. We analyzed values from 47 MMTT tests
      in 4 patients with up to 140 months follow-up and from 54 MMTT tests in 13
      patients with up to 42 months follow-up. SUITO, CP/G, HOMA2-B%, and BETA-2
      correlated well with the 90-minute glucose of the MMTT and beta-score (r 0.54
      0.76), whereas CP/GCr showed a modest performance (r 0.41-0.52) while TEF showed
      little correlation. BETA-2 and SUITO were the best identifiers and predictors of
      the need for insulin support, glucose intolerance, and ITx success (P < .001),
      while HOMA2-B% and TEF were unreliable. Single fasting blood sample SUITO and
      BETA-2 scores are very practical alternative tools that allow for frequent
      assessments of graft function.

PMID- 29218835
TI  - "We just follow the patients' lead": Healthcare professional perspectives on the
      involvement of teenagers with cancer in decision making.
AB  - PURPOSE: We report on an in-depth interview and participant observation study
      that uses data from multiple sources to determine how the involvement of
      teenagers with leukaemia is understood and enacted in healthcare. In this
      article, we investigate healthcare professionals' (HCP) views of teenagers'
      involvement in decisions about their care and treatment for leukaemia. METHODS:
      We conducted participant observation at 98 multi-disciplinary meetings and 95
      open-ended, semi-structured interviews and informal conversations with clinical
      teenage cancer teams at one UK tertiary referral centre. Data were collected over
      a 9-month period, audio-recorded, transcribed verbatim and analysed using
      principles of grounded theory. RESULTS: HCP revealed principles relating to the
      involvement of teenagers with leukaemia in decision making: (1) do the 'right
      thing', (2) act on the care and treatment preferences of the teenager and (3)
      openly disclose information about the teenagers' condition. These principles were
      prioritised and utilised uniquely in each situation, reliant on three mediating
      factors: (1) family communication styles, (2) stage of illness and (3) nature of
      the disease. CONCLUSIONS: Specialist haematology teams are aware of the
      individual, and shifting and situational preferences of teenagers. They follow
      the lead which teenagers give them with regard to these preferences. If actual
      practice with regard to the involvement of teenagers is found to be wanting, this
      study refutes that this should be ascribed to insensitivity on the part of HCP
      about teenagers informational and decisional role preferences.

PMID- 29218836
TI  - Model-Based Evaluation of Radiation and Radiosensitizing Agents in Oncology.
AB  - Radiotherapy is one of the major therapy forms in oncology, and combination
      therapies involving radiation and chemical compounds can yield highly effective
      tumor eradication. In this paper, we develop a tumor growth inhibition model for
      combination therapy with radiation and radiosensitizing agents. Moreover, we
      extend previous analyses of drug combinations by introducing the tumor static
      exposure (TSE) curve. The TSE curve for radiation and radiosensitizer visualizes
      exposure combinations sufficient for tumor regression. The model and TSE analysis
      are then tested on xenograft data. The calibrated model indicates that the
      highest dose of combination therapy increases the time until tumor regrowth 10
      fold. The TSE curve shows that with an average radiosensitizer concentration of
      1.0 MUg/mL the radiation dose can be decreased from 2.2 Gy to 0.7 Gy. Finally, we
      successfully predict the effect of a clinically relevant treatment schedule,
      which contributes to validating both the model and the TSE concept.

PMID- 29218837
TI  - Asthma in children and adolescents with type 1 diabetes in Germany and Austria:
      Frequency and metabolic control.
AB  - OBJECTIVE: To investigate the prevalence of asthma in young patients with type 1
      diabetes mellitus (T1D) from Austria and Germany and its influence on their
      metabolic control. METHODS: This prospective, multicenter observational cohort
      study was based on the DPV-registry (German/Austrian DPV initiative) including 51
      926 patients with T1D (<20 years). All clinical data were documented
      prospectively. To identify patients with additional asthma, the entry of the
      diagnosis asthma as well as asthma medication was used for classification.
      RESULTS: 1755 patients (3.4%) of the cohort had the diagnosis asthma or received
      asthma-specific drugs. Patients with asthma needed higher insulin doses (0.88 +/-
      0.3 vs 0.84 +/- 0.3 U/kg, P < .01) and had decreased height-standard deviation
      score (SDS) (-0.002 +/- 1.04 vs 0.085 +/- 1.02, P < .01); they were more often
      males (61% vs 52%, P < .01), had an increased body mass index (BMI)-SDS (0.31 +/-
      0.89 vs 0.28 +/- 0.89, P = .04) and experienced more severe hypoglycemia (4.5
      [4.2; 4.8] vs 3.2 [3.2; 3.3] events/100 pts. years, P < .01). Glycated hemoglobin
      A1c (HbA1c) did not differ between patients with and without asthma overall, only
      sub groups (corticosteroids vs leukotriene antagonist and corticosteroids vs
      sympatomimetics) revealed differences. No influence of asthma medication on
      metabolic control or BMI-SDS could be found. CONCLUSION: In our DPV-database,
      frequency of asthma and T1D seems similar to the prevalence of asthma in the
      healthy German background population. The concomitant diagnosis of asthma and T1D
      had minor influence on metabolic control and diabetes complication rate, although
      there was no difference in HbA1c overall. Patients with both diseases seem to be
      slightly growth restricted and require slightly higher insulin doses.

PMID- 29218838
TI  - Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified
      Poly(glycerol adipate) Nanoparticles.
AB  - Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate)
      (PGAS) are promising carriers for drug delivery. In order to investigate the
      impact of the particle interface characteristics on the biological fate, PGAS
      nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl)
      methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have
      similar particle sizes, but less negative zeta-potentials. Nanoparticles are
      double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676
      (covalently bound to HPMA copolymer), and their biodistribution is investigated
      noninvasively by multispectral optical imaging. Both covalent and noncovalent
      coatings cause changes in the pharmacokinetics and biodistribution in healthy and
      tumor-bearing mice. In addition to the intended tumor accumulation, high signals
      of both fluorescent dyes are also observed in other organs, including liver,
      ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers
      needs further detailed and systematic investigations, especially with respect to
      the observed ovarian and adrenal gland accumulation.

PMID- 29218839
TI  - Association between number of teeth, use of dentures and musculoskeletal frailty
      among older adults.
AB  - AIM: To assess whether there is a relationship between musculoskeletal frailty
      and number of teeth/denture use, and whether nutritional intake explains this
      relationship, in a sample of older Americans. METHODS: Data from the National
      Health and Nutrition Examination Survey 2011/2012 were used. Handgrip strength
      was used to show musculoskeletal frailty. Number of teeth and denture use were
      examined by calibrated dentists. Information on sociodemographic factors,
      nutrients intake and general health status were collected through interviews.
      Logistic regression models were used to assess the association between number of
      teeth/denture use by participants having <20 teeth and musculoskeletal frailty.
      Poisson regression analyses were used to assess the association between number of
      teeth/denture use and nutritional intake. RESULTS: There was no statistically
      significant difference in musculoskeletal frailty between denture users with <20
      teeth and those with >=20 teeth. Non-denture users with <20 teeth had higher odds
      for musculoskeletal frailty (OR 1.32, 95% CI 1.04-1.68). Accounting for
      nutritional intake explained >30% of this relationship. Having fewer teeth was
      associated with deficiency of nutritional intake regardless of denture use.
      CONCLUSIONS: Denture use is associated with lower chances of musculoskeletal
      frailty among older Americans. Nutritional intake explained approximately one
      third of the association, but most of the relationship was attributed to
      comorbidity. The findings imply that dental status might play a role in
      musculoskeletal frailty. Geriatr Gerontol Int 2018; 18: 592-598.

PMID- 29218840
TI  - Behaviour vs. perception: An investigation into the components of emotional
      invalidation.
AB  - BACKGROUND: The negative effects of emotionally invalidating environments are
      theorized by the biosocial theory of borderline personality disorder to be vast
      and severe. However, findings from studies on the impact of emotional
      invalidation (EI) vary, perhaps due to different operational definitions of EI.
      The current investigation seeks to explore the relationship between the objective
      behavioural observations of EI and recipient's subjective perceptions of
      experiencing these behaviours. METHOD: First, 58 participants watched scripted
      interactions between a confederate and a mock participant and identified the
      presence of invalidating and/or neutral behaviours. Next, 92 participants engaged
      in one-on-one interactions with a confederate utilizing the same scripted
      interactions observed by the first set of participants. RESULTS: While the first
      set of participants identified invalidating behaviours accurately and
      consistently, the participants who experienced the behaviours demonstrated more
      variability in their perceptions of the behaviours as emotionally invalidating.
      CONCLUSION: These preliminary findings demonstrate that the objective existence
      of emotionally invalidating behaviours are likely not the same as the experienced
      perception of EI across individuals, highlighting the need to examine how EI is
      operationally defined and measured. Future research should examine what
      individual characteristics may play a role in perceiving behaviours as
      emotionally invalidating. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29218842
TI  - Corrigendum: Highly Active N,O Zinc Guanidine Catalysts for the Ring-Opening
      Polymerization of Lactide.

PMID- 29218841
TI  - Improvement of conformal arc plans by using deformable margin delineation method
      for stereotactic lung radiotherapy.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) is an established treatment
      technique in the management of medically inoperable early stage non-small cell
      lung cancer (NSCLC). Different techniques such as volumetric modulated arc (VMAT)
      and three-dimensional conformal arc (DCA) can be used in SBRT. Previously, it has
      been shown that VMAT is superior to DCA technique in terms of plan evaluation
      parameters. However, DCA technique has several advantages such as ease of use and
      considerable shortening of the treatment time. DCA technique usually results in
      worse conformity which is not possible to ameliorate by inverse optimization. In
      this study, we aimed to analyze whether a simple method - deformable margin
      delineation (DMD) - improves the quality of the DCA technique, reaching similar
      results to VMAT in terms of plan evaluation parameters. METHODS: Twenty stage I
      II (T1-2, N0, M0) NSCLC patients were included in this retrospective dosimetric
      study. Noncoplanar VMAT and conventional DCA plans were generated using 6 MV and
      10 MV with flattening filter free (FFF) photon energies. The DCA plan with 6FFF
      was calculated and 95% of the PTV was covered by the prescription isodose line.
      Hot dose regions (receiving dose over 100% of prescription dose) outside PTV and
      cold dose regions (receiving dose under 100% of prescription dose) inside PTV
      were identified. A new PTV (PTV-DMD) was delineated by deforming PTV margin with
      respect to hot and cold spot regions obtained from conventional DCA plans.
      Dynamic multileaf collimators (MLC) were set to PTV-DMD beam eye view (BEV)
      positions and the new DCA plans (DCA-DMD) with 6FFF were generated. Three
      dimensional (3D) dose calculations were computed for PTV-DMD volume. However, the
      prescription isodose was specified and normalized to cover 95% volume of original
      PTV. Several conformity indices and lung doses were compared for different
      treatment techniques. RESULTS: DCA-DMD method significantly achieved a superior
      conformity index (CI), conformity number (CIPaddick ), gradient index (R50% ),
      isodose at 2 cm (D2 cm ) and external index (CDelta) with respect to VMAT and
      conventional DCA plans (P < 0.05 for all comparisons). CI ranged between 1.00
      1.07 (Mean: 1.02); 1.00-1.18 (Mean: 1.06); 1.01-1.23 (Mean 1.08); 1.03-1.29
      (Mean: 1.15); 1.04-1.29 (Mean: 1.18) for DCA-DMD-6FFF, VMAT-6FFF, VMAT-10FFF DCA
      6FFF and DCA-10FFF respectively. DCA-DMD-6FFF technique resulted significantly
      better CI compared to others (P = 0.002; < 0.001; < 0.001; < 0.001). R50% ranged
      between 3.22-4.74 (Mean: 3.99); 3.24-5.92 (Mean: 4.15) for DCA-DMD-6FFF, VMAT
      6FFF, respectively. DCA-DMD-6FFF technique resulted lower intermediate dose
      spillage compared to VMAT-6FFF, though the difference was statistically
      insignificant (P = 0.32). D2 cm ranged between 35.7% and 67.0% (Mean: 53.2%);
      42.1%-79.2% (Mean: 57.8%) for DCA-DMD-6FFF, VMAT-6FFF respectively. DCA-DMD-6FFF
      have significantly better and sharp falloff gradient 2 cm away from PTV compared
      to VMAT-6FFF (P = 0.009). CDelta ranged between 0.052 and 0.140 (Mean: 0.085);
      0,056-0,311 (Mean: 0.120) for DCA-DMD, VMAT-6FFF, respectively. DCA-DMD-6FFF have
      significantly improved CDelta (P = 0.002). VMAT- V20 Gy , V2.5 Gy and mean lung
      dose (MLD) indices are calculated to be 4.03%, 23.83%, 3.42 Gy and 4.19%,
      27.88%,3.72 Gy, for DCA-DMD-6FFF and DCA techniques, respectively. DCA-DMD-6FFF
      achieved superior lung sparing compared to DCA technique. DCA-DMD-6FFF method
      reduced MUs 44% and 33% with respect to VMAT-6FFF and 10FFF, respectively,
      without sacrificing dose conformity (P < 0.001; P < 0.001). CONCLUSIONS: Our
      results demonstrated that DCA plan evaluation parameters can be ameliorated by
      using the DMD method. This new method improves DCA plan quality and reaches
      similar results with VMAT in terms of dosimetric parameters. We believe that DCA
      DMD is a simple and effective technique for SBRT and can be preferred due to
      shorter treatment and planning time.

PMID- 29218843
TI  - Potential of saprophage Diptera to acquire culturable livestock-associated
      antibiotic-resistant bacteria.
AB  - The increasing prevalence of antibiotic resistance among bacteria is one of the
      most intractable challenges in 21st-century public health. Dipterans that
      associate with livestock, livestock waste products and cadavers have the
      potential to acquire livestock-associated antibiotic-resistant bacteria (LA-ARB)
      and transmit them to humans. In this study, piglet cadavers were used to attract
      saprophage dipterans from the environment and those dipterans were sampled for
      the presence of LA-ARB. In the first trial, culturable microbes resistant to both
      aminoglycoside and beta-lactam antibiotics were found in all cadavers and masses
      of dipteran larvae, and in three-quarters of adult dipterans. In the second
      trial, over 130 culturable bacterial colonies resistant to beta-lactams were
      isolated from the cadavers, larval and adult dipterans. Over 100 of those
      colonies were coliform or metabolically similar bacteria. Adult dipterans carried
      beta-lactam resistant staphylococci, whereas those bacterial types were absent
      from larval dipterans and cadavers, suggesting they were picked up from elsewhere
      in the environment. This research indicates that LA-ARB are ubiquitous in pig
      farms, and dipterans have the potential to carry medically important microbes.
      Further research is encouraged to determine the extent to which dipterans acquire
      microbes from animal agriculture relative to other environments.

PMID- 29218844
TI  - Predictors of hepatotoxicity and pancreatitis in children and adolescents with
      acute lymphoblastic leukemia treated according to contemporary regimens.
AB  - BACKGROUND: Hepatotoxicity and pancreatitis are common treatment-related
      toxicities (TRTs) during contemporary treatment regimens for acute lymphoblastic
      leukemia (ALL). Limited detailed data from Children's Oncology Group (COG)
      regimens has been previously reported to enable identification of patient and
      treatment risk factors for these toxicities and their impact on outcomes.
      PROCEDURE: We analyzed a retrospective pediatric ALL cohort treated at a single
      institution according to COG regimens from 2008 to 2015. The primary endpoint was
      cumulative incidence of study-defined "severe" hepatotoxicity (Common Terminology
      Criteria for Adverse Events [CTCAE] Grade >= 4 transaminitis or Grade >= 3
      hyperbilirubinemia) and clinically significant pancreatitis (any grade).
      Pancreatitis was additionally classified using the Ponte di Legno (PdL) toxicity
      criteria. Secondary endpoints were chemotherapy interruptions, early disease
      response (end of induction [EOI] minimal residual disease [MRD]), and event-free
      survival (EFS). RESULTS: We identified 262 patients, of whom 71 (27%) and 28
      (11%) developed hepatotoxicity and pancreatitis, respectively. Three cases of
      pancreatitis did not fulfill PdL criteria despite otherwise consistent
      presentations. Both TRTs occurred throughout therapy, but approximately 25% of
      hepatotoxicity (18/71) and pancreatitis (8/28) occurred during induction alone.
      Both obesity and age (>=10 years) were identified as predictors of hepatotoxicity
      (subdistribution hazard ratio [SHR] obesity = 1.75, 95% confidence interval [95%
      CI] 1.04-2.96; SHR age >=10 = 1.9, 95% CI 1.19-3.10) and pancreatitis (SHR
      obesity = 2.18, 95% CI 1.01-4.67; SHR age >= 10 = 2.76, 95% CI 1.19-6.39, P =
      0.018). Dose interruptions were common but neither toxicity influenced EOI MRD
      nor EFS. CONCLUSIONS: Obese and/or older children are particularly at risk for
      hepatotoxicity and pancreatitis, and may benefit from toxicity surveillance and
      chemoprotective strategies to prevent or mitigate associated morbidity.

PMID- 29218845
TI  - Probiotic consortia are not uniformly effective against different amphibian
      chytrid pathogen isolates.
AB  - Symbiotic bacterial communities can protect their hosts from infection by
      pathogens. Treatment of wild individuals with protective bacteria (probiotics)
      isolated from hosts can combat the spread of emerging infectious diseases.
      However, it is unclear whether candidate probiotic bacteria can offer consistent
      protection across multiple isolates of globally distributed pathogens. Here, we
      use the lethal amphibian fungal pathogen Batrachochytrium dendrobatidis to
      investigate whether probiotic richness (number of bacteria) or genetic distance
      among consortia members influences broad-scale in vitro inhibitory capabilities
      of probiotics across multiple isolates of the pathogen. We show that inhibition
      of multiple pathogen isolates by individual bacteria is rare, with no systematic
      pattern among bacterial genera in ability to inhibit multiple B. dendrobatidis
      isolates. Bacterial consortia can offer stronger protection against B.
      dendrobatidis compared to single strains, and this tended to be more pronounced
      for consortia containing multiple genera compared with those consisting of
      bacteria from a single genus (i.e., with lower genetic distance), but critically,
      this effect was not uniform across all B. dendrobatidis isolates. These novel
      insights have important implications for the effective design of bacterial
      probiotics to mitigate emerging infectious diseases.

PMID- 29218846
TI  - Revealing the Chemistry between Band Gap and Binding Energy for Lead-/Tin-Based
      Trihalide Perovskite Solar Cell Semiconductors.
AB  - A relationship between reported experimental band gaps (solid) and DFT-calculated
      binding energies (gas) is established, for the first time, for each of the four
      ten-membered lead (or tin) trihalide perovskite solar cell semiconductor series
      examined in this study, including CH3 NH3 PbY3 , CsPbY3 , CH3 NH3 SnY3 and CsSnY3
      (Y=I(3-x) Brx=1-3 , I(3-x) Clx=1-3 , Br(3-x) Cl x=1-3 , and IBrCl). The
      relationship unequivocally provides a new dimension for the fundamental
      understanding of the optoelectronic features of solid-state solar cell thin films
      by using the 0 K gas-phase energetics of the corresponding molecular building
      blocks.

PMID- 29218847
TI  - Potential exposure to Australian bat lyssavirus is unlikely to prevent future bat
      handling among adults in South East Queensland.
AB  - Despite ongoing public health messages about the risks associated with bat
      contact, the number of potential exposures to Australian bat lyssavirus (ABLV)
      due to intentional handling by members of the general public in Queensland has
      remained high. We sought to better understand the reasons for intentional
      handling among these members of the public who reported their potential exposure
      to inform future public health messages. We interviewed adults who resided in a
      defined geographic area in South East Queensland and notified potential exposure
      to ABLV due to intentional handling of bats by telephone between 1 January 2012
      and 31 December 2013. The participation rate was 54%. Adults who reported they
      had intentionally handled bats in South East Queensland indicated high levels of
      knowledge and perception of a moderately high risk associated with bats with
      overall low intentions to handle bats in the future. However, substantial
      proportions of people would attempt to handle bats again in some circumstances,
      particularly to protect their children or pets. Fifty-two percent indicated that
      they would handle a bat if a child was about to pick up or touch a live bat, and
      49% would intervene if a pet was interacting with a bat. Future public health
      communications should recognize the situations in which even people with highrisk
      perceptions of bats will attempt to handle them. Public health messages currently
      focus on avoidance of bats in all circumstances and recommend calling in a
      trained vaccinated handler, but messaging directed at adults for circumstances
      where children or pets may be potentially exposed should provide safe immediate
      management options.

PMID- 29218848
TI  - SHANK1 is differentially expressed during development in CA1 hippocampal neurons
      and astrocytes.
AB  - Recent studies have strongly suggested a role for the synaptic scaffolding
      protein SHANK1 in normal synaptic structure and signaling. Global SHANK1 knockout
      (SHANK1-/-) mice demonstrate reduced dendritic spine density, an immature
      dendritic spine phenotype and impairments in various cognitive tasks. SHANK1
      overexpression is associated with increased dendritic spine size and impairments
      in fear conditioning. These studies suggest proper regulation of SHANK1 is
      crucial for appropriate synaptic structure and cognition. However, little is
      known regarding SHANK1's developmental expression in brain regions critical for
      learning. The current study quantified cell specific developmental expression of
      SHANK1 in the hippocampus, a brain region critically involved in various learning
      paradigms shown to be disrupted by SHANK1 dysregulation. Consistent with prior
      studies, SHANK1 was found to be strongly co-expressed with dendritic markers,
      with significant increased co-expression at postnatal day (P) 15, an age
      associated with increased synaptogenesis in the hippocampus. Interestingly,
      SHANK1 was also found to be expressed in astrocytes and microglia. To our
      knowledge, this is the first demonstration of glial SHANK1 localization;
      therefore, these findings were further examined via a glial purified primary cell
      culture fraction using magnetic cell sorting. This additional analysis further
      demonstrated that SHANK1 was expressed in glial cells, supporting our
      immunofluorescence co-expression findings. Developmentally, astroglial SHANK1 co
      expression was found to be significantly elevated at P5 with a reduction into
      adulthood, while SHANK1 microglial co-expression did not significantly change
      across development. These data collectively implicate a more global role for
      SHANK1 in mediating normal cellular signaling in the brain. (c) 2017 Wiley
      Periodicals, Inc. Develop Neurobiol 78: 363-373, 2018.

PMID- 29218849
TI  - Reconstruction of full-thickness cheek defect with chimeric facial artery free
      flap: A case report.
AB  - Full-thickness cheek defects represent a difficult challenge for reconstructive
      surgeons. Multiple techniques have been described, including local, regional, and
      free flaps. In this report, the reconstruction of a through and through left
      cheek defect, resulting from a self-inflicted gunshot injury, with a chimeric
      facial artery free flap is presented. The patient underwent reconstruction with a
      chimeric full-thickness facial artery free flap, with 9 * 3 cm diameter skin
      paddle and a 6 * 5 cm myomucosal paddle, was harvested on the contralateral cheek
      with a 7-cm length of facial pedicle. The flap was transferred via a
      microsurgical technique and an end-to-end microsurgical anastomosis was performed
      between the donor and the contralateral facial vessels. The flap was transplanted
      successfully and there were no donor or recipient site complications with a
      satisfactory esthetic result 5 years after surgery. This technique may be a good
      reconstructive option for medium size, full-thickness, cheek defects allowing a
      "like with like" reconstruction with minimal donor-site morbidity.

PMID- 29218850
TI  - Characterization of auxin transporter PIN6 plasma membrane targeting reveals a
      function for PIN6 in plant bolting.
AB  - Auxin gradients are sustained by series of influx and efflux carriers whose
      subcellular localization is sensitive to both exogenous and endogenous factors.
      Recently the localization of the Arabidopsis thaliana auxin efflux carrier PIN
      FORMED (PIN) 6 was reported to be tissue-specific and regulated through unknown
      mechanisms. Here, we used genetic, molecular and pharmacological approaches to
      characterize the molecular mechanism(s) controlling the subcellular localization
      of PIN6. PIN6 localizes to endomembrane domains in tissues with low PIN6
      expression levels such as roots, but localizes at the plasma membrane (PM) in
      tissues with increased PIN6 expression such as the inflorescence stem and nectary
      glands. We provide evidence that this dual localization is controlled by PIN6
      phosphorylation and demonstrate that PIN6 is phosphorylated by mitogen-activated
      protein kinases (MAPKs) MPK4 and MPK6. The analysis of transgenic plants
      expressing PIN6 at PM or in endomembrane domains reveals that PIN6 subcellular
      localization is critical for Arabidopsis inflorescence stem elongation post
      flowering (bolting). In line with a role for PIN6 in plant bolting, inflorescence
      stems elongate faster in pin6 mutant plants than in wild-type plants. We propose
      that PIN6 subcellular localization is under the control of developmental signals
      acting on tissue-specific determinants controlling PIN6-expression levels and
      PIN6 phosphorylation.

PMID- 29218851
TI  - Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for
      relapsed and refractory acute myeloid leukemia and related myeloid malignancies.
AB  - INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent
      activity in relapsed and refractory (R/R) acute myeloid leukemia (AML), and
      efficacy in lower intensity combinations for treatment-naive elderly AML
      patients. VEN treatment combinations in R/R AML have not been previously
      reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic
      syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated
      with VEN combinations in the salvage setting were reviewed. RESULTS: Forty-three
      patients with median age 68 (range, 25-83) were treated for AML (91%), MDS (5%),
      or BPDCN (5%). Most (n = 36, 84%) were >= salvage-2 treatment status, including
      prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients
      received HMA therapy (n = 31, 72%); eight (19%) received low-dose cytarabine
      (LDAC). Patients received a median of 2 treatment cycles (range, 1-4). Objective
      response was observed in 9 (21%) patients, including 2 complete responses (CR), 3
      CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months
      (range, 0.5-8.0), and estimated 6-month survival was 24%. Responses were observed
      in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11
      IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53
      mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%)
      responding patients with adverse cytogenetics, all had concurrent RUNX1
      mutations. CONCLUSION: Low-intensity chemotherapy, including HMAs or LDAC, in
      combination with VEN is a viable salvage option, even in multiply
      relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were
      identified in patients with diploid/intermediate cytogenetics, RUNX1, and/or
      IDH1/2 mutations.

PMID- 29218852
TI  - Psychotic conversion of individuals at ultra-high risk for psychosis: The
      potential roles of schizotypy and basic symptoms.
AB  - AIM: To improve strategies for the early identification of individuals at a
      heightened risk for the development of psychosis, we investigated the
      relationships and interactions between 3 psychosis-proneness dimensions for the
      development of schizophrenia spectrum psychosis: schizotypy, basic symptoms and
      the ultra-high risk (UHR) criteria. METHODS: Seventy-seven UHR individuals and 79
      healthy controls were assessed for schizotypy and basic symptoms using self
      report questionnaires at baseline. UHR participants were monthly assessed for
      conversion to psychosis over a mean period of 25.8 months. RESULTS: Sixteen UHR
      participants (20.8%) converted to schizophrenia spectrum psychosis. In stepwise
      Cox regression, the interaction between basic symptoms and physical anhedonia was
      selected as a sole predictor of conversion in UHR participants, whereby the self
      reported number of the 8 basic symptoms significantly increased the risk for
      conversion in those with pronounced physical anhedonia. CONCLUSION: Our findings
      suggest that questionnaire-assessed basic symptoms, irrespective of their
      predictive validity, may predict a psychotic breakdown in pre-identified UHR
      individuals who are with genetic vulnerability to schizophrenia. Including all 3
      psychosis-proneness dimensions into prediction models might help establish a more
      valid pathogenetic model of schizophrenia, and moreover, may provide some clues
      about course alteration strategies in hopes of preventing UHR individuals from
      converting to psychosis.

PMID- 29218853
TI  - RNA-sequencing identifies novel GREB1-NCOA2 fusion gene in a uterine sarcoma with
      the chromosomal translocation t(2;8)(p25;q13).
AB  - Sarcomas account for 3% of all uterine malignancies and many of them are
      characterized by acquired, specific fusion genes whose detection has increased
      pathogenetic knowledge and diagnostic precision. We describe a novel fusion gene,
      GREB1-NCOA2, detected by transcriptome sequencing and validated by reverse
      transcriptase polymerase chain reaction and Sanger sequencing in an
      undifferentiated uterine sarcoma. The chimeric transcript was an in-frame fusion
      between exon 3 of GREB1 and exon 15 of NCOA2. The fusion is reported here for the
      first time, but it involves the GREB1 gene, an important promoter of tumor growth
      and progression, and NCOA2 which is known to be involved in transcriptional
      regulation. The alteration and recombination of these genes played a role in the
      tumorigenesis and/or progression of this sarcoma.

PMID- 29218854
TI  - Achieving Nearly 30% External Quantum Efficiency for Orange-Red Organic Light
      Emitting Diodes by Employing Thermally Activated Delayed Fluorescence Emitters
      Composed of 1,8-Naphthalimide-Acridine Hybrids.
AB  - The combination of rigid acridine donor and 1,8-naphthalimide acceptor has
      afforded two orange-red emitters of NAI-DMAC and NAI-DPAC with high rigidity in
      molecular structure and strongly pretwisted charge transfer state. Endowed with
      high photoluminescence quantum yields (PhiPL ), distinct thermally activated
      delayed fluorescence (TADF) characteristics, and preferentially horizontal
      emitting dipole orientations, these emitters afford record-high orange-red TADF
      organic light-emitting diodes (OLEDs) with external quantum efficiencies of up to
      21-29.2%, significantly surpassing all previously reported orange-to-red TADF
      OLEDs. Notably, the influence of microcavity effect is verified to support the
      record-high efficiency. This finding relaxes the usually stringent material
      requirements for effective TADF emitters by comprising smaller radiative
      transition rates and less than ideal PhiPL s.

PMID- 29218855
TI  - Effects of prior exposure to antibiotics on bacterial adaptation to phages.
AB  - Understanding adaptation to complex environments requires information about how
      exposure to one selection pressure affects adaptation to others. For bacteria,
      antibiotics and viral parasites (phages) are two of the most common selection
      pressures and are both relevant for treatment of bacterial infections: increasing
      antibiotic resistance is generating significant interest in using phages in
      addition or as an alternative to antibiotics. However, we lack knowledge of how
      exposure to antibiotics affects bacterial responses to phages. Specifically, it
      is unclear how the negative effects of antibiotics on bacterial population growth
      combine with any possible mutagenic effects or physiological responses to
      influence adaptation to other stressors such as phages, and how this net effect
      varies with antibiotic concentration. Here, we experimentally addressed the
      effect of pre-exposure to a wide range of antibiotic concentrations on bacterial
      responses to phages. Across 10 antibiotics, we found a strong association between
      their effects on bacterial population size and subsequent population growth in
      the presence of phages (which in these conditions indicates phage-resistance
      evolution). We detected some evidence of mutagenesis among populations treated
      with fluoroquinolones and beta-lactams at sublethal doses, but these effects were
      small and not consistent across phage treatments. These results show that,
      although stressors such as antibiotics can boost adaptation to other stressors at
      low concentrations, these effects are weak compared to the effect of reduced
      population growth at inhibitory concentrations, which in our experiments strongly
      reduced the likelihood of subsequent phage-resistance evolution.

PMID- 29218856
TI  - Preparation of fluoride-loaded microcapsules for anticariogenic bacterial growth
      using a coaxial ultrasonic atomizer.
AB  - A new method to deliver fluoride using biodegradable poly(lactic-co-glycolic
      acid) microcapsules to suppress cariogenic bacterial growth during orthodontic
      treatment was investigated. A coaxial ultrasonic atomizer was used to encapsulate
      KF solution into microcapsules. The orthodontic adhesive resin disk containing
      fluoride loaded microcapsules (DFLM) was prepared by LED light curing. The
      microstructure of microcapsules, successful loading of KF, fracture strength, and
      shear bonding strength were assessed by FE-SEM, confocal laser scanning
      microscope, and general purpose testing machine, respectively. Fluoride release
      from the DFLM in phosphate buffered saline and pH changes were measured after
      different periods of soaking time. Antibacterial activity of the DFLM was
      assessed in tryptic soy broth containing mutant streptococci. The starting
      inoculum and the orthodontic resin disk containing microcapsules not loaded with
      KF were used as negative and positive controls, respectively. As results, the
      cumulative amount of KF after 49 days was about 85% of the initial amount of
      fluoride contained in the microcapsules. The fracture and shear bonding strengths
      of the orthodontic resin disks with and without the microcapsules were similar to
      each other. The DFLM showed lower bacterial growth than the control groups,
      whereas no statistically significant differences were found between the negative
      and positive controls. It can be concluded that the microcapsules loaded with
      fluoride prepared by a coaxial ultrasonic atomizer have good potential for
      application as an antibacterial agent due to their excellent cariogenic
      antibacterial activity when incorporated into orthodontic adhesive resin. (c)
      2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 31
      39, 2018.

PMID- 29218857
TI  - The combined effect of thermal and chemotherapy on HeLa cells using magnetically
      actuated smart textured fibrous system.
AB  - Thermal therapy combined with chemotherapy is one of the advanced and efficient
      methods to eradicate cancer. In this work, we fabricated magnetically actuated
      smart textured (MAST) fibrous systems and studied their candidacy for cancer
      treatment. The polycaprolactone-Fe3 O4 based MAST fibers were fabricated using
      electrospinning technique. These MAST fibrous systems contained carbogenic
      quantum dots as a tracking agent and doxorubicin hydrochloride anticancer drug.
      Additionally, as fabricated MAST fibrous systems were able to deliver anticancer
      drug and heat energy simultaneously to kill HeLa cells in a 10 min period in
      vitro. After treatment, the metabolic activity and morphology of HeLa cells were
      analyzed. In addition, the mechanism of cell death was studied using flow
      cytometry. Interestingly, the navigation of these systems in the fluid can be
      controlled with the application of gradient magnetic field. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 40-51, 2018.

PMID- 29218858
TI  - In vitro and in vivo study of commercial calcium phosphate cement HydroSetTM.
AB  - The commercial calcium phosphate cement, HydroSetTM, was investigated in vitro,
      studying phase formation, compressive strength and setting time, followed by an
      ovine in vivo study to measure osseointegration, bone apposition and bone-to
      graft contact. The X-ray diffraction and 31 P Magic Angle Spinning Nuclear
      Magnetic Resonance (MAS NMR) results showed the initial formation of octacalcium
      phosphate and hydroxyapatite at one hour. Over 7 days the octacalcium phosphate
      transformed to apatite, which was the only crystalline phase of the cement at 28
      days. This apatite phase is thought to be a calcium deficient apatite. In the
      scanning electron microscopy, histological images of 12-week ovine in vivo
      results showed a high degree of osseointegration, 92.5%. Compressive strength
      comparisons between in vitro and in vivo measurements showed a dramatic
      difference between the in vitro measurements (highest 25.4 MPa) and in vivo (95
      MPa), attributed to bone ingrowth into the cement in vivo. To the best of our
      knowledge this is the first time phase evolution of HydroSetTM and the properties
      studied in vitro complement the in vivo evaluation of the cement in a
      publication. The significance of the new finding of initial formation of
      octacalcium phosphate in this cement is discussed. (c) 2016 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 21-30, 2018.

PMID- 29218859
TI  - Looking for new approaches for the use of serology in the context of control
      programmes against pig salmonellosis.
AB  - Most swine Salmonella national control programmes in Europe have been based on
      the categorization of herds according to risk levels based on serological
      results. However, none of the non-Scandinavian countries have reported of any
      significant success on Salmonella infection reduction in fattening pigs or the
      number of human cases attributable to pigs or pork. The limited accuracy of the
      tests used, the small number of animals sampled and the likely lack of herd
      representativeness of the samples used could be major factors affecting the
      suitability of these programmes. Focusing on minimizing Salmonella shedding at
      slaughter appears more important to prevent human infections than focusing on
      detection of seropositive pigs/herds at this stage. This study assessed whether
      performing on-farm serology may help to predict shedding at slaughter. Between
      2010 and 2016, pigs from six cohorts from a Salmonella-positive herd were bled at
      30, 60 and 90 days on fattening and before slaughter, and faecal samples
      collected at slaughter. Serology on days 60, 90 and before slaughter predicted
      somewhat shedding at slaughter with no significant differences among them. Pigs
      with higher OD% values at these point times would have higher risk of shedding
      when arriving to slaughter. The probability of shedding for a pig sampled on day
      90 and showing an OD% value of 10 was 43%, and the risk increased up to 65% if
      the OD% was 40. Concluding, on-farm serology may help to determine to some extent
      the risk of Salmonella shedding at slaughter from seropositive fattening units,
      which would allow for prompt on-farm and slaughter interventions to reduce the
      likelihood of slaughter contamination with Salmonella.

PMID- 29218860
TI  - 32nd International Epilepsy Congress Barcelona, Spain 2nd - 6th September 2017.

PMID- 29218861
TI  - Comparative expression patterns of Sox2 and Sox19 genes in the forebrain of
      developing and adult turbot (Scophthalmus maximus).
AB  - The turbot, Scophthalmus maximus, belongs to the flatfishes (order
      Pleuronectiformes), which display substantial asymmetry of the olfactory organs
      and forebrain. Sox genes code for SRY-related HMG domain-bearing transcription
      factors involved in various developmental processes. Group B1 Sox genes as Sox2
      and Sox19 appear to play major roles in neural development. Here, we
      characterized by in situ hybridization the developmental expression of Sox2 and
      Sox19 genes in metamorphic and postmetamorphic specimens and young adults of both
      sexes. Expression of S. maximus Sox2 (Sm-Sox2) and Sm-Sox19 mRNAs was detected in
      ependymal cells of different regions of the telencephalon, preoptic region,
      hypothalamus, and thalamus at all stages investigated. Sm-Sox2 expression but not
      Sm-Sox19 occurred in neurons located in particular regions such as the dorsal
      nucleus of the ventral telencephalon, the medial zone of the dorsal
      telencephalon, preoptic area and hypothalamus. Although Sm-Sox2 and Sm-Sox19 are
      expressed differentially in gonads, no sex differences in their expression were
      observed between male and female forebrains. We also investigated the
      topographical relation between Sox expression and cell proliferation using series
      double immunostained for a radial glial marker (BLBP) and cell proliferation
      marker (PCNA). Sm-Sox2 and Sm-Sox19 were strongly expressed in ependymal cells
      located in neurogenic niches revealed by the BLBP and PCNA immunostaining.
      Comparison with other teleosts indicates similar expression of Sox2 and Sox19 in
      the telencephalon, supporting conserved roles for both genes in teleost brains.

PMID- 29218862
TI  - The presence and distribution of cannabinoid type 1 and 2 receptors in the
      mandibular gland: The influence of different physical forms of diets on their
      expression in piglets.
AB  - We explored the expression and cell type distribution of cannabinoid receptors
      type 1 (CB1) and cannabinoid receptors type 2 (CB2) in the mandibular glands of
      pigs in relation to different physical forms of the diet. Thirty-two crossbred
      growing pigs (ages 5-6 weeks) were randomly allotted to four experimental groups
      (eight pigs/group) and fed four different physical types of the same diet for 4
      weeks: finely ground pellet (FP), coarsely ground meal (CM), coarsely ground
      pellet (CP) and coarsely ground extruded (CE) with dMEAN of 0.46, 0.88, 0.84 and
      0.66 mm respectively. At the end of the feeding trial, the pigs were euthanized
      and the mandibular gland was collected after dissection. By immunohistochemistry,
      positive signals for CB1 were found in the cytoplasm of duct epithelial cells of
      pigs fed CP, FP and CE diets and in the serous cells of mixed acini in pigs fed
      the coarser CM diet. Positive signals for CB2 were detected in duct epithelial
      cells and in neurons of ganglia close to major secretory ducts of all pigs. The
      differential expression and localization of these receptors in response to
      variable chewing activity due to the type of diet suggest that endocannabinoids
      may influence the functional activity of the mandibular gland by modifying
      qualitative and/or quantitative aspects of salivary secretion.

PMID- 29218863
TI  - Population structure and migration of the Tobacco Blue Mold Pathogen, Peronospora
      tabacina, into North America and Europe.
AB  - : Tobacco blue mold, caused by Peronospora tabacina, is an oomycete plant
      pathogen that causes yearly epidemics in tobacco (Nicotiana tabacum) in the
      United States and Europe. The genetic structure of P. tabacina was examined to
      understand genetic diversity, population structure and patterns of migration. Two
      nuclear loci, Igs2 and Ypt1, and one mitochondrial locus, cox2, were amplified,
      cloned and sequenced from fifty-four isolates of P. tabacina from the United
      States, Central America-Caribbean-Mexico (CCAM), Europe and the Middle East
      (EULE). Cloned sequences from the three genes showed high genetic variability
      across all populations. Nucleotide diversity and the population mean mutation
      parameter per site (Watterson's theta) were higher in EULE and CCAM and lower in
      U.S. POPULATIONS: Neutrality tests were significant and the equilibrium model of
      neutral evolution was rejected, indicating an excess of recent mutations or rare
      alleles. Hudson's Snn tests were performed to examine population subdivision and
      gene flow among populations. An isolation-with-migration analysis (IM) supported
      the hypothesis of long-distance migration of P. tabacina from the Caribbean
      region, Florida and Texas into other states in the United States. Within the
      European populations, the model documented migration from North Central Europe
      into western Europe and Lebanon, and migration from western Europe into Lebanon.
      The migration patterns observed support historical observations about the first
      disease introductions and movement in Europe. The models developed are applicable
      to other aerial dispersed emerging pathogens and document that high-evolutionary
      risk plant pathogens can move over long distances to cause disease due to their
      large effective population size, population expansion and dispersal.

PMID- 29218864
TI  - APPLICATIONS OF GENETICS, GENOMICS AND BIOINFORMATICS IN DRUG DISCOVERY.
AB  - As the impact of genetics, genomics, and bioinformatics on drug discovery has
      been increasingly recognized, this session of the 2018 Pacific Symposium on
      Biocomputing (PSB) aims to facilitate scientific discussions between academia and
      pharmaceutical industry on how to best apply genetics, genomics and
      bioinformatics to enable drug discovery. The selected papers focus on developing
      and applying computational approaches to understand drug mechanisms of action and
      develop drug combination strategies, to enable in silico drug screening, and to
      further delineate disease pathways for target identification and validation.

PMID- 29218865
TI  - Characterization of drug-induced splicing complexity in prostate cancer cell line
      using long read technology.
AB  - We characterize the transcriptional splicing landscape of a prostate cancer cell
      line treated with a previously identified synergistic drug combination. We use a
      combination of third generation long-read RNA sequencing technology and short
      read RNAseq to create a high-fidelity map of expressed isoforms and fusions to
      quantify splicing events triggered by treatment. We find strong evidence for drug
      induced, coherent splicing changes which disrupt the function of oncogenic
      proteins, and detect novel transcripts arising from previously unreported fusion
      events.

PMID- 29218866
TI  - Prediction of protein-ligand interactions from paired protein sequence motifs and
      ligand substructures.
AB  - Identification of small molecule ligands that bind to proteins is a critical step
      in drug discovery. Computational methods have been developed to accelerate the
      prediction of protein-ligand binding, but often depend on 3D protein structures.
      As only a limited number of protein 3D structures have been resolved, the ability
      to predict protein-ligand interactions without relying on a 3D representation
      would be highly valuable. We use an interpretable confidence-rated boosting
      algorithm to predict protein-ligand interactions with high accuracy from ligand
      chemical substructures and protein 1D sequence motifs, without relying on 3D
      protein structures. We compare several protein motif definitions, assess
      generalization of our model's predictions to unseen proteins and ligands,
      demonstrate recovery of well established interactions and identify globally
      predictive protein-ligand motif pairs. By bridging biological and chemical
      perspectives, we demonstrate that it is possible to predict protein-ligand
      interactions using only motif-based features and that interpretation of these
      features can reveal new insights into the molecular mechanics underlying each
      interaction. Our work also lays a foundation to explore more predictive feature
      sets and sophisticated machine learning approaches as well as other applications,
      such as predicting unintended interactions or the effects of mutations.

PMID- 29218867
TI  - Cell-specific prediction and application of drug-induced gene expression
      profiles.
AB  - Gene expression profiling of in vitro drug perturbations is useful for many
      biomedical discovery applications including drug repurposing and elucidation of
      drug mechanisms. However, limited data availability across cell types has
      hindered our capacity to leverage or explore the cell-specificity of these
      perturbations. While recent efforts have generated a large number of drug
      perturbation profiles across a variety of human cell types, many gaps remain in
      this combinatorial drug-cell space. Hence, we asked whether it is possible to
      fill these gaps by predicting cell-specific drug perturbation profiles using
      available expression data from related conditions--i.e. from other drugs and cell
      types. We developed a computational framework that first arranges existing
      profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and
      cell types, and then uses either local (nearest-neighbors) or global (tensor
      completion) information to predict unmeasured profiles. We evaluate prediction
      accuracy using a variety of metrics, and find that the two methods have
      complementary performance, each superior in different regions in the drug-cell
      space. Predictions achieve correlations of 0.68 with true values, and maintain
      accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that
      the predicted profiles add value for making downstream associations with drug
      targets and therapeutic classes.

PMID- 29218868
TI  - Large-scale integration of heterogeneous pharmacogenomic data for identifying
      drug mechanism of action.
AB  - A variety of large-scale pharmacogenomic data, such as perturbation experiments
      and sensitivity profiles, enable the systematical identification of drug
      mechanism of actions (MoAs), which is a crucial task in the era of precision
      medicine. However, integrating these complementary pharmacogenomic datasets is
      inherently challenging due to the wild heterogeneity, high-dimensionality and
      noisy nature of these datasets. In this work, we develop Mania, a novel method
      for the scalable integration of large-scale pharmacogenomic data. Mania first
      constructs a drug-drug similarity network through integrating multiple
      heterogeneous data sources, including drug sensitivity, drug chemical structure,
      and perturbation assays. It then learns a compact vector representation for each
      drug to simultaneously encode its structural and pharmacogenomic properties.
      Extensive experiments demonstrate that Mania achieves substantially improved
      performance in both MoAs and targets prediction, compared to predictions based on
      individual data sources as well as a state-of-the-art integrative method.
      Moreover, Mania identifies drugs that target frequently mutated cancer genes,
      which provides novel insights into drug repurposing.

PMID- 29218869
TI  - Chemical reaction vector embeddings: towards predicting drug metabolism in the
      human gut microbiome.
AB  - Bacteria in the human gut have the ability to activate, inactivate, and
      reactivate drugs with both intended and unintended effects. For example, the drug
      digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut
      Actinobacterium E. lenta, and patients colonized with high levels of drug
      metabolizing strains may have limited response to the drug. Understanding the
      complete space of drugs that are metabolized by the human gut microbiome is
      critical for predicting bacteria-drug relationships and their effects on
      individual patient response. Discovery and validation of drug metabolism via
      bacterial enzymes has yielded >50 drugs after nearly a century of experimental
      research. However, there are limited computational tools for screening drugs for
      potential metabolism by the gut microbiome. We developed a pipeline for comparing
      and characterizing chemical transformations using continuous vector
      representations of molecular structure learned using unsupervised representation
      learning. We applied this pipeline to chemical reaction data from MetaCyc to
      characterize the utility of vector representations for chemical reaction
      transformations. After clustering molecular and reaction vectors, we performed
      enrichment analyses and queries to characterize the space. We detected enriched
      enzyme names, Gene Ontology terms, and Enzyme Consortium (EC) classes within
      reaction clusters. In addition, we queried reactions against drug-metabolite
      transformations known to be metabolized by the human gut microbiome. The top
      results for these known drug transformations contained similar substructure
      modifications to the original drug pair. This work enables high throughput
      screening of drugs and their resulting metabolites against chemical reactions
      common to gut bacteria.

PMID- 29218871
TI  - Extracting a biologically relevant latent space from cancer transcriptomes with
      variational autoencoders.
AB  - The Cancer Genome Atlas (TCGA) has profiled over 10,000 tumors across 33
      different cancer-types for many genomic features, including gene expression
      levels. Gene expression measurements capture substantial information about the
      state of each tumor. Certain classes of deep neural network models are capable of
      learning a meaningful latent space. Such a latent space could be used to explore
      and generate hypothetical gene expression profiles under various types of
      molecular and genetic perturbation. For example, one might wish to use such a
      model to predict a tumor's response to specific therapies or to characterize
      complex gene expression activations existing in differential proportions in
      different tumors. Variational autoencoders (VAEs) are a deep neural network
      approach capable of generating meaningful latent spaces for image and text data.
      In this work, we sought to determine the extent to which a VAE can be trained to
      model cancer gene expression, and whether or not such a VAE would capture
      biologically-relevant features. In the following report, we introduce a VAE
      trained on TCGA pan-cancer RNA-seq data, identify specific patterns in the VAE
      encoded features, and discuss potential merits of the approach. We name our
      method "Tybalt" after an instigative, cat-like character who sets a cascading
      chain of events in motion in Shakespeare's "Romeo and Juliet". From a systems
      biology perspective, Tybalt could one day aid in cancer stratification or predict
      specific activated expression patterns that would result from genetic changes or
      treatment effects.

PMID- 29218870
TI  - Loss-of-function of neuroplasticity-related genes confers risk for human
      neurodevelopmental disorders.
AB  - High and increasing prevalence of neurodevelopmental disorders place enormous
      personal and economic burdens on society. Given the growing realization that the
      roots of neurodevelopmental disorders often lie in early childhood, there is an
      urgent need to identify childhood risk factors. Neurodevelopment is marked by
      periods of heightened experience-dependent neuroplasticity wherein neural
      circuitry is optimized by the environment. If these critical periods are
      disrupted, development of normal brain function can be permanently altered,
      leading to neurodevelopmental disorders. Here, we aim to systematically identify
      human variants in neuroplasticity-related genes that confer risk for
      neurodevelopmental disorders. Historically, this knowledge has been limited by a
      lack of techniques to identify genes related to neurodevelopmental plasticity in
      a high-throughput manner and a lack of methods to systematically identify
      mutations in these genes that confer risk for neurodevelopmental disorders. Using
      an integrative genomics approach, we determined loss-of-function (LOF) variants
      in putative plasticity genes, identified from transcriptional profiles of brain
      from mice with elevated plasticity, that were associated with neurodevelopmental
      disorders. From five shared differentially expressed genes found in two mouse
      models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/-
      relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe
      Biobank we identified multiple associations between LOF genes and increased risk
      for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai
      Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work
      demonstrates a novel approach to identify neurodevelopmental risk genes and
      points toward a promising avenue to discover new drug targets to address the
      unmet therapeutic needs of neurodevelopmental disease.

PMID- 29218872
TI  - Diffusion mapping of drug targets on disease signaling network elements reveals
      drug combination strategies.
AB  - The emergence of drug resistance to traditional chemotherapy and newer targeted
      therapies in cancer patients is a major clinical challenge. Reactivation of the
      same or compensatory signaling pathways is a common class of drug resistance
      mechanisms. Employing drug combinations that inhibit multiple modules of
      reactivated signaling pathways is a promising strategy to overcome and prevent
      the onset of drug resistance. However, with thousands of available FDA-approved
      and investigational compounds, it is infeasible to experimentally screen millions
      of possible drug combinations with limited resources. Therefore, computational
      approaches are needed to constrain the search space and prioritize synergistic
      drug combinations for preclinical studies. In this study, we propose a novel
      approach for predicting drug combinations through investigating potential effects
      of drug targets on disease signaling network. We first construct a disease
      signaling network by integrating gene expression data with disease-associated
      driver genes. Individual drugs that can partially perturb the disease signaling
      network are then selected based on a drug-disease network "impact matrix", which
      is calculated using network diffusion distance from drug targets to signaling
      network elements. The selected drugs are subsequently clustered into communities
      (subgroups), which are proposed to share similar mechanisms of action. Finally,
      drug combinations are ranked according to maximal impact on signaling sub
      networks from distinct mechanism-based communities. Our method is advantageous
      compared to other approaches in that it does not require large amounts drug dose
      response data, drug-induced "omics" profiles or clinical efficacy data, which are
      not often readily available. We validate our approach using a BRAF-mutant
      melanoma signaling network and combinatorial in vitro drug screening data, and
      report drug combinations with diverse mechanisms of action and opportunities for
      drug repositioning.

PMID- 29218873
TI  - Session Introduction: Challenges of Pattern Recognition in Biomedical Data.
AB  - The analysis of large biomedical data often presents with various challenges
      related to not just the size of the data, but also to data quality issues such as
      heterogeneity, multidimensionality, noisiness, and incompleteness of the data.
      The data-intensive nature of computational genomics problems in biomedical
      informatics warrants the development and use of massive computer infrastructure
      and advanced software tools and platforms, including but not limited to the use
      of cloud computing. Our session aims to address these challenges in handling big
      data for designing a study, performing analysis, and interpreting outcomes of
      these analyses. These challenges have been prevalent in many studies including
      those which focus on the identification of novel genetic variant-phenotype
      associations using data from sources like Electronic Health Records (EHRs) or
      multi-omic data. One of the biggest challenges to focus on is the imperfect
      nature of the biomedical data where a lot of noise and sparseness is observed. In
      our session, we will present research articles that can help in identifying
      innovative ways to recognize and overcome newly arising challenges associated
      with pattern recognition in biomedical data.

PMID- 29218874
TI  - Large-scale analysis of disease pathways in the human interactome.
AB  - Discovering disease pathways, which can be defined as sets of proteins associated
      with a given disease, is an important problem that has the potential to provide
      clinically actionable insights for disease diagnosis, prognosis, and treatment.
      Computational methods aid the discovery by relying on protein-protein interaction
      (PPI) networks. They start with a few known disease-associated proteins and aim
      to find the rest of the pathway by exploring the PPI network around the known
      disease proteins. However, the success of such methods has been limited, and
      failure cases have not been well understood. Here we study the PPI network
      structure of 519 disease pathways. We find that 90% of pathways do not correspond
      to single well-connected components in the PPI network. Instead, proteins
      associated with a single disease tend to form many separate connected
      components/regions in the network. We then evaluate state-of-the-art disease
      pathway discovery methods and show that their performance is especially poor on
      diseases with disconnected pathways. Thus, we conclude that network connectivity
      structure alone may not be sufficient for disease pathway discovery. However, we
      show that higher-order network structures, such as small subgraphs of the
      pathway, provide a promising direction for the development of new methods.

PMID- 29218875
TI  - Mapping Patient Trajectories using Longitudinal Extraction and Deep Learning in
      the MIMIC-III Critical Care Database.
AB  - Electronic Health Records (EHRs) contain a wealth of patient data useful to
      biomedical researchers. At present, both the extraction of data and methods for
      analyses are frequently designed to work with a single snapshot of a patient's
      record. Health care providers often perform and record actions in small batches
      over time. By extracting these care events, a sequence can be formed providing a
      trajectory for a patient's interactions with the health care system. These care
      events also offer a basic heuristic for the level of attention a patient receives
      from health care providers. We show that is possible to learn meaningful
      embeddings from these care events using two deep learning techniques,
      unsupervised autoencoders and long short-term memory networks. We compare these
      methods to traditional machine learning methods which require a point in time
      snapshot to be extracted from an EHR.

PMID- 29218876
TI  - OWL-NETS: Transforming OWL Representations for Improved Network Inference.
AB  - Our knowledge of the biological mechanisms underlying complex human disease is
      largely incomplete. While Semantic Web technologies, such as the Web Ontology
      Language (OWL), provide powerful techniques for representing existing knowledge,
      well-established OWL reasoners are unable to account for missing or uncertain
      knowledge. The application of inductive inference methods, like machine learning
      and network inference are vital for extending our current knowledge. Therefore,
      robust methods which facilitate inductive inference on rich OWL-encoded knowledge
      are needed. Here, we propose OWL-NETS (NEtwork Transformation for Statistical
      learning), a novel computational method that reversibly abstracts OWL-encoded
      biomedical knowledge into a network representation tailored for network
      inference. Using several examples built with the Open Biomedical Ontologies, we
      show that OWL-NETS can leverage existing ontology-based knowledge representations
      and network inference methods to generate novel, biologically-relevant
      hypotheses. Further, the lossless transformation of OWL-NETS allows for seamless
      integration of inferred edges back into the original knowledge base, extending
      its coverage and completeness.

PMID- 29218877
TI  - Automated disease cohort selection using word embeddings from Electronic Health
      Records.
AB  - Accurate and robust cohort definition is critical to biomedical discovery using
      Electronic Health Records (EHR). Similar to prospective study designs, high
      quality EHR-based research requires rigorous selection criteria to designate
      case/control status particular to each disease. Electronic phenotyping
      algorithms, which are manually built and validated per disease, have been
      successful in filling this need. However, these approaches are time-consuming,
      leading to only a relatively small amount of algorithms for diseases developed.
      Methodologies that automatically learn features from EHRs have been used for
      cohort selection as well. To date, however, there has been no systematic analysis
      of how these methods perform against current gold standards. Accordingly, this
      paper compares the performance of a state-of-the-art automated feature learning
      method to extracting research-grade cohorts for five diseases against their
      established electronic phenotyping algorithms. In particular, we use word2vec to
      create unsupervised embeddings of the phenotype space within an EHR system. Using
      medical concepts as a query, we then rank patients by their proximity in the
      embedding space and automatically extract putative disease cohorts via a distance
      threshold. Experimental evaluation shows promising results with average F-score
      of 0.57 and AUC-ROC of 0.98. However, we noticed that results varied considerably
      between diseases, thus necessitating further investigation and/or phenotype
      specific refinement of the approach before being readily deployed across all
      diseases.

PMID- 29218878
TI  - Functional network community detection can disaggregate and filter multiple
      underlying pathways in enrichment analyses.
AB  - Differential expression experiments or other analyses often end in a list of
      genes. Pathway enrichment analysis is one method to discern important biological
      signals and patterns from noisy expression data. However, pathway enrichment
      analysis may perform suboptimally in situations where there are multiple
      implicated pathways - such as in the case of genes that define subtypes of
      complex diseases. Our simulation study shows that in this setting, standard
      overrepresentation analysis identifies many false positive pathways along with
      the true positives. These false positives hamper investigators' attempts to glean
      biological insights from enrichment analysis. We develop and evaluate an approach
      that combines community detection over functional networks with pathway
      enrichment to reduce false positives. Our simulation study demonstrates that a
      large reduction in false positives can be obtained with a small decrease in
      power. Though we hypothesized that multiple communities might underlie previously
      described subtypes of high-grade serous ovarian cancer and applied this approach,
      our results do not support this hypothesis. In summary, applying community
      detection before enrichment analysis may ease interpretation for complex gene
      sets that represent multiple distinct pathways.

PMID- 29218879
TI  - An ultra-fast and scalable quantification pipeline for transposable elements from
      next generation sequencing data.
AB  - Transposable elements (TEs) are DNA sequences which are capable of moving from
      one location to another and represent a large proportion (45%) of the human
      genome. TEs have functional roles in a variety of biological phenomena such as
      cancer, neurodegenerative disease, and aging. Rapid development in RNA-sequencing
      technology has enabled us, for the first time, to study the activity of TE at the
      systems level.However, efficient TE analysis tools are not yet developed. In this
      work, we developed SalmonTE, a fast and reliable pipeline for the quantification
      of TEs from RNA-seq data. We benchmarked our tool against TEtranscripts, a widely
      used TE quantification method, and three other quantification methods using
      several RNA-seq datasets from Drosophila melanogaster and human cell-line. We
      achieved 20 times faster execution speed without compromising the accuracy. This
      pipeline will enable the biomedical research community to quantify and analyze
      TEs from large amounts of data and lead to novel TE centric discoveries.

PMID- 29218880
TI  - Causal inference on electronic health records to assess blood pressure treatment
      targets: an application of the parametric g formula.
AB  - Hypertension is a major risk factor for ischemic cardiovascular disease and
      cerebrovascular disease, which are respectively the primary and secondary most
      common causes of morbidity and mortality across the globe. To alleviate the risks
      of hypertension, there are a number of effective antihypertensive drugs
      available. However, the optimal treatment blood pressure goal for
      antihypertensive therapy remains an area of controversy. The results of the
      recent Systolic Blood Pressure Intervention Trial (SPRINT) trial, which found
      benefits for intensive lowering of systolic blood pressure, have been debated for
      several reasons. We aimed to assess the benefits of treating to four different
      blood pressure targets and to compare our results to those of SPRINT using a
      method for causal inference called the parametric g formula. We applied this
      method to blood pressure measurements obtained from the electronic health records
      of approximately 200,000 patients who visited the Mount Sinai Hospital in New
      York, NY. We simulated the effect of four clinically relevant dynamic treatment
      regimes, assessing the effectiveness of treating to four different blood pressure
      targets: 150 mmHg, 140 mmHg, 130 mmHg, and 120 mmHg. In contrast to current
      American Heart Association guidelines and in concordance with SPRINT, we find
      that targeting 120 mmHg systolic blood pressure is significantly associated with
      decreased incidence of major adverse cardiovascular events. Causal inference
      methods applied to electronic methods are a powerful and flexible technique and
      medicine may benefit from their increased usage.

PMID- 29218881
TI  - Data-driven advice for applying machine learning to bioinformatics problems.
AB  - As the bioinformatics field grows, it must keep pace not only with new data but
      with new algorithms. Here we contribute a thorough analysis of 13 state-of-the
      art, commonly used machine learning algorithms on a set of 165 publicly available
      classification problems in order to provide data-driven algorithm recommendations
      to current researchers. We present a number of statistical and visual comparisons
      of algorithm performance and quantify the effect of model selection and algorithm
      tuning for each algorithm and dataset. The analysis culminates in the
      recommendation of five algorithms with hyperparameters that maximize classifier
      performance across the tested problems, as well as general guidelines for
      applying machine learning to supervised classification problems.

PMID- 29218882
TI  - Improving the explainability of Random Forest classifier - user centered
      approach.
AB  - Machine Learning (ML) methods are now influencing major decisions about patient
      care, new medical methods, drug development and their use and importance are
      rapidly increasing in all areas. However, these ML methods are inherently complex
      and often difficult to understand and explain resulting in barriers to their
      adoption and validation. Our work (RFEX) focuses on enhancing Random Forest (RF)
      classifier explainability by developing easy to interpret explainability summary
      reports from trained RF classifiers as a way to improve the explainability for
      (often non-expert) users. RFEX is implemented and extensively tested on Stanford
      FEATURE data where RF is tasked with predicting functional sites in 3D molecules
      based on their electrochemical signatures (features). In developing RFEX method
      we apply user-centered approach driven by explainability questions and
      requirements collected by discussions with interested practitioners. We performed
      formal usability testing with 13 expert and non-expert users to verify RFEX
      usefulness. Analysis of RFEX explainability report and user feedback indicates
      its usefulness in significantly increasing explainability and user confidence in
      RF classification on FEATURE data. Notably, RFEX summary reports easily reveal
      that one needs very few (from 2-6 depending on a model) top ranked features to
      achieve 90% or better of the accuracy when all 480 features are used.

PMID- 29218883
TI  - Tree-based Methods for Characterizing Tumor Density Heterogeneity.
AB  - Solid lesions emerge within diverse tissue environments making their
      characterization and diagnosis a challenge. With the advent of cancer radiomics,
      a variety of techniques have been developed to transform images into quantifiable
      feature sets producing summary statistics that describe the morphology and
      texture of solid masses. Relying on empirical distribution summaries as well as
      grey-level co-occurrence statistics, several approaches have been devised to
      characterize tissue density heterogeneity. This article proposes a novel decision
      tree based approach which quantifies the tissue density heterogeneity of a given
      lesion through its resultant distribution of tree-structured dissimilarity
      metrics computed with least common ancestor trees under repeated pixel re
      sampling. The methodology, based on statistics derived from Galton-Watson trees,
      produces metrics that are minimally correlated with existing features, adding new
      information to the feature space and improving quantitative characterization of
      the extent to which a CT image conveys heterogeneous density distribution. We
      demonstrate its practical application through a diagnostic study of adrenal
      lesions. Integrating the proposed with existing features identifies classifiers
      of three important lesion types; malignant from benign (AUC = 0.78), functioning
      from non-functioning (AUC = 0.93) and calcified from non-calcified (AUC of 1).

PMID- 29218885
TI  - Democratizing Health Data for Translational Research.
AB  - There is an expanding and intensive focus on the accessibility, reproducibility,
      and rigor of basic, clinical, and translational research. This focus complements
      the need to identify sustainable ways to generate actionable research results
      that improve human health. The principles and practices of open science offer a
      promising path to address both issues by facilitating: 1) increased transparency
      of data and methods which promotes research reproducibility and rigor; and 2)
      cumulative efficiencies wherein research tools and the output of research are
      combined to accelerate the delivery of new knowledge. While great strides have
      been in made in terms of enabling the open science paradigm in the biological
      sciences, progress in sharing of patient-derived health data has been more
      moderate. This lack of widespread access to common and well characterized health
      data is a substantial impediment to the timely, efficient, and multi-disciplinary
      conduct of translational research, particularly in those instances where
      hypotheses spanning multiple scales (from molecules to patients to populations)
      are being developed and tested. To address such challenges, we review current
      best practices and lessons learned, and explore the need for policy changes and
      technical innovation that can enhance the sharing of health data for
      translational research.

PMID- 29218884
TI  - How powerful are summary-based methods for identifying expression-trait
      associations under different genetic architectures?
AB  - Transcriptome-wide association studies (TWAS) have recently been employed as an
      approach that can draw upon the advantages of genome-wide association studies
      (GWAS) and gene expression studies to identify genes associated with complex
      traits. Unlike standard GWAS, summary level data suffices for TWAS and offers
      improved statistical power. Two popular TWAS methods include either (a) imputing
      the cis genetic component of gene expression from smaller sized studies (using
      multi-SNP prediction or MP) into much larger effective sample sizes afforded by
      GWAS - TWAS-MP or (b) using summary-based Mendelian randomization - TWAS-SMR.
      Although these methods have been effective at detecting functional variants, it
      remains unclear how extensive variability in the genetic architecture of complex
      traits and diseases impacts TWAS results. Our goal was to investigate the
      different scenarios under which these methods yielded enough power to detect
      significant expression-trait associations. In this study, we conducted extensive
      simulations based on 6000 randomly chosen, unrelated Caucasian males from
      Geisinger's MyCode population to compare the power to detect cis expression-trait
      associations (within 500 kb of a gene) using the above-described approaches. To
      test TWAS across varying genetic backgrounds we simulated gene expression and
      phenotype using different quantitative trait loci per gene and cis-expression
      /trait heritability under genetic models that differentiate the effect of
      causality from that of pleiotropy. For each gene, on a training set ranging from
      100 to 1000 individuals, we either (a) estimated regression coefficients with
      gene expression as the response using five different methods: LASSO, elastic net,
      Bayesian LASSO, Bayesian spike-slab, and Bayesian ridge regression or (b)
      performed eQTL analysis. We then sampled with replacement 50,000, 150,000, and
      300,000 individuals respectively from the testing set of the remaining 5000
      individuals and conducted GWAS on each set. Subsequently, we integrated the GWAS
      summary statistics derived from the testing set with the weights (or eQTLs)
      derived from the training set to identify expression-trait associations using (a)
      TWAS-MP (b) TWAS-SMR (c) eQTL-based GWAS, or (d) standalone GWAS. Finally, we
      examined the power to detect functionally relevant genes using the different
      approaches under the considered simulation scenarios. In general, we observed
      great similarities among TWAS-MP methods although the Bayesian methods resulted
      in improved power in comparison to LASSO and elastic net as the trait
      architecture grew more complex while training sample sizes and expression
      heritability remained small. Finally, we observed high power under causality but
      very low to moderate power under pleiotropy.

PMID- 29218886
TI  - ClinGen Cancer Somatic Working Group - standardizing and democratizing access to
      cancer molecular diagnostic data to drive translational research.
AB  - A growing number of academic and community clinics are conducting genomic testing
      to inform treatment decisions for cancer patients (1). In the last 3-5 years,
      there has been a rapid increase in clinical use of next generation sequencing
      (NGS) based cancer molecular diagnostic (MolDx) testing (2). The increasing
      availability and decreasing cost of tumor genomic profiling means that physicians
      can now make treatment decisions armed with patient-specific genetic information.
      Accumulating research in the cancer biology field indicates that there is
      significant potential to improve cancer patient outcomes by effectively
      leveraging this rich source of genomic data in treatment planning (3). To achieve
      truly personalized medicine in oncology, it is critical to catalog cancer
      sequence variants from MolDx testing for their clinical relevance along with
      treatment information and patient outcomes, and to do so in a way that supports
      large-scale data aggregation and new hypothesis generation. One critical
      challenge to encoding variant data is adopting a standard of annotation of those
      variants that are clinically actionable. Through the NIH-funded Clinical Genome
      Resource (ClinGen) (4), in collaboration with NLM's ClinVar database and >50
      academic and industry based cancer research organizations, we developed the
      Minimal Variant Level Data (MVLD) framework to standardize reporting and
      interpretation of drug associated alterations (5). We are currently involved in
      collaborative efforts to align the MVLD framework with parallel, complementary
      sequence variants interpretation clinical guidelines from the Association of
      Molecular Pathologists (AMP) for clinical labs (6). In order to truly democratize
      access to MolDx data for care and research needs, these standards must be
      harmonized to support sharing of clinical cancer variants. Here we describe the
      processes and methods developed within the ClinGen's Somatic WG in collaboration
      with over 60 cancer care and research organizations as well as CLIA-certified,
      CAP-accredited clinical testing labs to develop standards for cancer variant
      interpretation and sharing.

PMID- 29218887
TI  - A heuristic method for simulating open-data of arbitrary complexity that can be
      used to compare and evaluate machine learning methods.
AB  - A central challenge of developing and evaluating artificial intelligence and
      machine learning methods for regression and classification is access to data that
      illuminates the strengths and weaknesses of different methods. Open data plays an
      important role in this process by making it easy for computational researchers to
      easily access real data for this purpose. Genomics has in some examples taken a
      leading role in the open data effort starting with DNA microarrays. While real
      data from experimental and observational studies is necessary for developing
      computational methods it is not sufficient. This is because it is not possible to
      know what the ground truth is in real data. This must be accompanied by simulated
      data where that balance between signal and noise is known and can be directly
      evaluated. Unfortunately, there is a lack of methods and software for simulating
      data with the kind of complexity found in real biological and biomedical systems.
      We present here the Heuristic Identification of Biological Architectures for
      simulating Complex Hierarchical Interactions (HIBACHI) method and prototype
      software for simulating complex biological and biomedical data. Further, we
      introduce new methods for developing simulation models that generate data that
      specifically allows discrimination between different machine learning methods.

PMID- 29218888
TI  - Identifying natural health product and dietary supplement information within
      adverse event reporting systems.
AB  - Data on safety and efficacy issues associated with natural health products and
      dietary supplements (NHP&S) remains largely cloistered within domain specific
      databases or embedded within general biomedical data sources. A major challenge
      in leveraging analytic approaches on such data is due to the inefficient ability
      to retrieve relevant data, which includes a general lack of interoperability
      among related sources. This study developed a thesaurus of NHP&S ingredient terms
      that can be used by existing biomedical natural language processing (NLP) tools
      for extracting information of interest. This process was evaluated relative to
      intervention name strings sampled from the United States Food and Drug
      Administration Adverse Event Reporting System (FAERS). A use case was used to
      demonstrate the potential to utilize FAERS for monitoring NHP&S adverse events.
      The results from this study provide insights on approaches for identifying
      additional knowledge from extant repositories of knowledge, and potentially as
      information that can be included into larger curation efforts.

PMID- 29218889
TI  - Best practices and lessons learned from reuse of 4 patient-derived metabolomics
      datasets in Alzheimer's disease.
AB  - The importance of open data has been increasingly recognized in recent years.
      Although the sharing and reuse of clinical data for translational research lags
      behind best practices in biological science, a number of patient-derived datasets
      exist and have been published enabling translational research spanning multiple
      scales from molecular to organ level, and from patients to populations. In
      seeking to replicate metabolomic biomarker results in Alzheimer's disease our
      team identified three independent cohorts in which to compare findings. Accessing
      the datasets associated with these cohorts, understanding their content and
      provenance, and comparing variables between studies was a valuable exercise in
      exploring the principles of open data in practice. It also helped inform steps
      taken to make the original datasets available for use by other researchers. In
      this paper we describe best practices and lessons learned in attempting to
      identify, access, understand, and analyze these additional datasets to advance
      research reproducibility, as well as steps taken to facilitate sharing of our own
      data.

PMID- 29218890
TI  - Democratizing data science through data science training.
AB  - The biomedical sciences have experienced an explosion of data which promises to
      overwhelm many current practitioners. Without easy access to data science
      training resources, biomedical researchers may find themselves unable to wrangle
      their own datasets. In 2014, to address the challenges posed such a data
      onslaught, the National Institutes of Health (NIH) launched the Big Data to
      Knowledge (BD2K) initiative. To this end, the BD2K Training Coordinating Center
      (TCC; bigdatau.org) was funded to facilitate both in-person and online learning,
      and open up the concepts of data science to the widest possible audience. Here,
      we describe the activities of the BD2K TCC and its focus on the construction of
      the Educational Resource Discovery Index (ERuDIte), which identifies, collects,
      describes, and organizes online data science materials from BD2K awardees, open
      online courses, and videos from scientific lectures and tutorials. ERuDIte now
      indexes over 9,500 resources. Given the richness of online training materials and
      the constant evolution of biomedical data science, computational methods applying
      information retrieval, natural language processing, and machine learning
      techniques are required - in effect, using data science to inform training in
      data science. In so doing, the TCC seeks to democratize novel insights and
      discoveries brought forth via large-scale data science training.

PMID- 29218891
TI  - IMAGING GENOMICS.
AB  - The following sections are included:IntroductionOverview of
      ContributionsReferences.

PMID- 29218892
TI  - Heritability estimates on resting state fMRI data using ENIGMA analysis pipeline.
AB  - Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta
      Analysis consortium (ENIGMA), combine data collected by independent studies
      worldwide to achieve more generalizable estimates of effect sizes and more
      reliable and reproducible outcomes. Such efforts require harmonized image
      analyses protocols to extract phenotypes consistently. This harmonization is
      particularly challenging for resting state fMRI due to the wide variability of
      acquisition protocols and scanner platforms; this leads to site-to-site variance
      in quality, resolution and temporal signal-to-noise ratio (tSNR). An effective
      harmonization should provide optimal measures for data of different qualities. We
      developed a multi-site rsfMRI analysis pipeline to allow research groups around
      the world to process rsfMRI scans in a harmonized way, to extract consistent and
      quantitative measurements of connectivity and to perform coordinated statistical
      tests. We used the single-modality ENIGMA rsfMRI preprocessing pipeline based on
      modelfree Marchenko-Pastur PCA based denoising to verify and replicate resting
      state network heritability estimates. We analyzed two independent cohorts, GOBS
      (Genetics of Brain Structure) and HCP (the Human Connectome Project), which
      collected data using conventional and connectomics oriented fMRI protocols,
      respectively. We used seed-based connectivity and dual-regression approaches to
      show that the rsfMRI signal is consistently heritable across twenty major
      functional network measures. Heritability values of 20-40% were observed across
      both cohorts.

PMID- 29218893
TI  - Discriminative bag-of-cells for imaging-genomics.
AB  - Connecting genotypes to image phenotypes is crucial for a comprehensive
      understanding of cancer. To learn such connections, new machine learning
      approaches must be developed for the better integration of imaging and genomic
      data. Here we propose a novel approach called Discriminative Bag-of-Cells (DBC)
      for predicting genomic markers using imaging features, which addresses the
      challenge of summarizing histopathological images by representing cells with
      learned discriminative types, or codewords. We also developed a reliable and
      efficient patch-based nuclear segmentation scheme using convolutional neural
      networks from which nuclear and cellular features are extracted. Applying DBC on
      TCGA breast cancer samples to predict basal subtype status yielded a class
      balanced accuracy of 70% on a separate test partition of 213 patients. As data
      sets of imaging and genomic data become increasingly available, we believe DBC
      will be a useful approach for screening histopathological images for genomic
      markers. Source code of nuclear segmentation and DBC are available at:
      https://github.com/bchidest/DBC.

PMID- 29218894
TI  - MRI to MGMT: predicting methylation status in glioblastoma patients using
      convolutional recurrent neural networks.
AB  - Glioblastoma Multiforme (GBM), a malignant brain tumor, is among the most lethal
      of all cancers. Temozolomide is the primary chemotherapy treatment for patients
      diagnosed with GBM. The methylation status of the promoter or the enhancer
      regions of the O6-methylguanine methyltransferase (MGMT) gene may impact the
      efficacy and sensitivity of temozolomide, and hence may affect overall patient
      survival. Microscopic genetic changes may manifest as macroscopic morphological
      changes in the brain tumors that can be detected using magnetic resonance imaging
      (MRI), which can serve as noninvasive biomarkers for determining methylation of
      MGMT regulatory regions. In this research, we use a compendium of brain MRI scans
      of GBM patients collected from The Cancer Imaging Archive (TCIA) combined with
      methylation data from The Cancer Genome Atlas (TCGA) to predict the methylation
      state of the MGMT regulatory regions in these patients. Our approach relies on a
      bi-directional convolutional recurrent neural network architecture (CRNN) that
      leverages the spatial aspects of these 3-dimensional MRI scans. Our CRNN obtains
      an accuracy of 67% on the validation data and 62% on the test data, with
      precision and recall both at 67%, suggesting the existence of MRI features that
      may complement existing markers for GBM patient stratification and prognosis. We
      have additionally presented our model via a novel neural network visualization
      platform, which we have developed to improve interpretability of deep learning
      MRI-based classification models.

PMID- 29218895
TI  - Deep Integrative Analysis for Survival Prediction.
AB  - Survival prediction is very important in medical treatment. However, recent
      leading research is challenged by two factors: 1) the datasets usually come with
      multi-modality; and 2) sample sizes are relatively small. To solve the above
      challenges, we developed a deep survival learning model to predict patients'
      survival outcomes by integrating multi-view data. The proposed network contains
      two sub-networks, one view-specific and one common sub-network. We designated one
      CNN-based and one FCN-based sub-network to efficiently handle pathological images
      and molecular profiles, respectively. Our model first explicitly maximizes the
      correlation among the views and then transfers feature hierarchies from view
      commonality and specifically fine-tunes on the survival prediction task. We
      evaluate our method on real lung and brain tumor data sets to demonstrate the
      effectiveness of the proposed model using data with multiple modalities across
      different tumor types.

PMID- 29218896
TI  - Genotype-phenotype association study via new multi-task learning model.
AB  - Research on the associations between genetic variations and imaging phenotypes is
      developing with the advance in high-throughput genotype and brain image
      techniques. Regression analysis of single nucleotide polymorphisms (SNPs) and
      imaging measures as quantitative traits (QTs) has been proposed to identify the
      quantitative trait loci (QTL) via multi-task learning models. Recent studies
      consider the interlinked structures within SNPs and imaging QTs through group
      lasso, e.g. l2, 1-norm, leading to better predictive results and insights of
      SNPs. However, group sparsity is not enough for representing the correlation
      between multiple tasks and l2, 1-norm regularization is not robust either. In
      this paper, we propose a new multi-task learning model to analyze the
      associations between SNPs and QTs. We suppose that low-rank structure is also
      beneficial to uncover the correlation between genetic variations and imaging
      phenotypes. Finally, we conduct regression analysis of SNPs and QTs. Experimental
      results show that our model is more accurate in prediction than compared methods
      and presents new insights of SNPs.

PMID- 29218897
TI  - Codon bias among synonymous rare variants is associated with Alzheimer's disease
      imaging biomarker.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with few biomarkers even
      though it impacts a relatively large portion of the population and is predicted
      to affect significantly more individuals in the future. Neuroimaging has been
      used in concert with genetic information to improve our understanding in relation
      to how AD arises and how it can be potentially diagnosed. Additionally, evidence
      suggests synonymous variants can have a functional impact on gene regulatory
      mechanisms, including those related to AD. Some synonymous codons are preferred
      over others leading to a codon bias. The bias can arise with respect to codons
      that are more or less frequently used in the genome. A bias can also result from
      optimal and non-optimal codons, which have stronger and weaker codon anti-codon
      interactions, respectively. Although association tests have been utilized before
      to identify genes associated with AD, it remains unclear how codon bias plays a
      role and if it can improve rare variant analysis. In this work, rare variants
      from whole-genome sequencing from the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) cohort were binned into genes using BioBin. An association analysis of the
      genes with AD-related neuroimaging biomarker was performed using SKAT-O. While
      using all synonymous variants we did not identify any genomewide significant
      associations, using only synonymous variants that affected codon frequency we
      identified several genes as significantly associated with the imaging phenotype.
      Additionally, significant associations were found using only rare variants that
      contains an optimal codon in among minor alleles and a non-optimal codon in the
      major allele. These results suggest that codon bias may play a role in AD and
      that it can be used to improve detection power in rare variant association
      analysis.

PMID- 29218898
TI  - Building trans-omics evidence: using imaging and 'omics' to characterize cancer
      profiles.
AB  - Utilization of single modality data to build predictive models in cancer results
      in a rather narrow view of most patient profiles. Some clinical facet s relate
      strongly to histology image features, e.g. tumor stages, whereas others are
      associated with genomic and proteomic variations (e.g. cancer subtypes and
      disease aggression biomarkers). We hypothesize that there are coherent "trans
      omics" features that characterize varied clinical cohorts across multiple sources
      of data leading to more descriptive and robust disease characterization. In this
      work, for l 05 breast cancer patients from the TCGA (The Cancer Genome Atlas), we
      consider four clinical attributes (AJCC Stage, Tumor Stage, ER-Status and PAM50
      mRNA Subtypes), and build predictive models using three different modalities of
      data (histopathological images, transcriptomics and proteomics). Following which,
      we identify critical multi-level features that drive successful classification of
      patients for the various different cohorts. To build predictors for each data
      type, we employ widely used "best practice" techniques including CNN-based
      (convolutional neural network) classifiers for histopathological images and
      regression models for proteogenomic data. While, as expected, histology images
      outperformed molecular features while predicting cancer stages, and
      transcriptomics held superior discriminatory power for ER-Status and PAM50
      subtypes, there exist a few cases where all data modalities exhibited comparable
      performance. Further, we also identified sets of key genes and proteins whose
      expression and abundance correlate across each clinical cohort including (i)
      tumor severity and progression (incl. GABARAP), (ii) ER-status (incl.ESRl) and
      (iii) disease subtypes (incl. FOXCl). Thus, we quantitatively assess the efficacy
      of different data types to predict critical breast cancer patient attributes and
      improve disease characterization.

PMID- 29218899
TI  - PRECISION MEDICINE: FROM DIPLOTYPES TO DISPARITIES TOWARDS IMPROVED HEALTH AND
      THERAPIES.
AB  - Precision medicine research efforts both in basic science discovery and clinical
      implementation are well underway and promise to provide individualized
      preventions and treatments, improving overall health care delivery. To achieve
      these goals, advances in data capture and analysis are needed spanning different
      types of 'omic and clinical data. The efforts to enhance precise treatments for
      all may accentuate healthcare disparities unless specific challenges are
      identified and addressed. This session of the 2018 Pacific Symposium on
      Biocomputing presents the latest developments in this transdisciplinary research
      space of genomics, medicine, and population health.

PMID- 29218900
TI  - Single subject transcriptome analysis to identify functionally signed gene set or
      pathway activity.
AB  - Analysis of single-subject transcriptome response data is an unmet need of
      precision medicine, made challenging by the high dimension, dynamic nature and
      difficulty in extracting meaningful signals from biological or stochastic noise.
      We have proposed a method for single subject analysis that uses a mixture model
      for transcript fold-change clustering from isogenically paired samples, followed
      by integration of these distributions with Gene Ontology Biological Processes (GO
      BP) to reduce dimension and identify functional attributes. We then extended
      these methods to develop functional signing metrics for gene set process
      regulation by incorporating biological repressor relationships encoded in GO-BP
      as negatively_regulates edges. Results revealed reproducible and biologically
      meaningful signals from analysis of a single subject's response, opening the door
      to future transcriptomic studies where subject and resource availability are
      currently limiting. We used inbred mouse strains fed different diets to provide
      isogenic biological replicates, permitting rigorous validation of our method. We
      compared significant genotype-specific GO-BP term results for overlap and rank
      order across three replicate pairs per genotype, and cross-methods to reference
      standards (limma+FET, SAM+FET, and GSEA). All single-subject analytics findings
      were robust and highly reproducible (median area under the ROC curve=0.96, n=24
      genotypes * 3 replicates), providing confidence and validation of this approach
      for analyses in single subjects. R code is available online at
      http://www.lussiergroup.org/publications/PathwayActivity.

PMID- 29218901
TI  - Using simulation and optimization approach to improve outcome through warfarin
      precision treatment.
AB  - We apply a treatment simulation and optimization approach to develop decision
      support guidance for warfarin precision treatment plans. Simulation include the
      use of ~1,500,000 clinical avatars (simulated patients) generated by an
      integrated data-driven and domain-knowledge based Bayesian Network Modeling
      approach. Subsequently, we simulate 30-day individual patient response to
      warfarin treatment of five clinical and genetic treatment plans followed by both
      individual and subpopulation based optimization. Sub-population optimization
      (compared to individual optimization) provides a cost effective and realistic
      means of implementation of a precision-driven treatment plan in practical
      settings. In this project, we use the property of minimal entropy to minimize
      overall adverse risks for the largest possible patient sub-populations and we
      temper the results by considering both transparency and ease of implementation.
      Finally, we discuss the improved outcome of the precision treatment plan based on
      the sub-population optimized decision support rules.

PMID- 29218902
TI  - Local ancestry transitions modify snp-trait associations.
AB  - Genomic maps of local ancestry identify ancestry transitions - points on a
      chromosome where recent recombination events in admixed individuals have joined
      two different ancestral haplotypes. These events bring together alleles that
      evolved within separate continential populations, providing a unique opportunity
      to evaluate the joint effect of these alleles on health outcomes. In this work,
      we evaluate the impact of genetic variants in the context of nearby local
      ancestry transitions within a sample of nearly 10,000 adults of African ancestry
      with traits derived from electronic health records. Genetic data was located
      using the Metabochip, and used to derive local ancestry. We develop a model that
      captures the effect of both single variants and local ancestry, and use it to
      identify examples where local ancestry transitions significantly interact with
      nearby variants to influence metabolic traits. In our most compelling example, we
      find that the minor allele of rs16890640 occuring on a European background with a
      downstream local ancestry transition to African ancestry results in significantly
      lower mean corpuscular hemoglobin and volume. This finding represents a new way
      of discovering genetic interactions, and is supported by molecular data that
      suggest changes to local ancestry may impact local chromatin looping.

PMID- 29218903
TI  - Coalitional game theory as a promising approach to identify candidate autism
      genes.
AB  - Despite mounting evidence for the strong role of genetics in the phenotypic
      manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible
      for the variable forms of ASD remain undefined. ASD may be best explained by a
      combinatorial genetic model with varying epistatic interactions across many small
      effect mutations. Coalitional or cooperative game theory is a technique that
      studies the combined effects of groups of players, known as coalitions, seeking
      to identify players who tend to improve the performance--the relationship to a
      specific disease phenotype--of any coalition they join. This method has been
      previously shown to boost biologically informative signal in gene expression data
      but to-date has not been applied to the search for cooperative mutations among
      putative ASD genes. We describe our approach to highlight genes relevant to ASD
      using coalitional game theory on alteration data of 1,965 fully sequenced genomes
      from 756 multiplex families. Alterations were encoded into binary matrices for
      ASD (case) and unaffected (control) samples, indicating likely gene-disrupting,
      inherited mutations in altered genes. To determine individual gene contributions
      given an ASD phenotype, a "player" metric, referred to as the Shapley value, was
      calculated for each gene in the case and control cohorts. Sixty seven genes were
      found to have significantly elevated player scores and likely represent
      significant contributors to the genetic coordination underlying ASD. Using
      network and cross-study analysis, we found that these genes are involved in
      biological pathways known to be affected in the autism cases and that a subset
      directly interact with several genes known to have strong associations to autism.
      These findings suggest that coalitional game theory can be applied to large-scale
      genomic data to identify hidden yet influential players in complex polygenic
      disorders such as autism.

PMID- 29218905
TI  - Considerations for automated machine learning in clinical metabolic profiling:
      Altered homocysteine plasma concentration associated with metformin exposure.
AB  - With the maturation of metabolomics science and proliferation of biobanks,
      clinical metabolic profiling is an increasingly opportunistic frontier for
      advancing translational clinical research. Automated Machine Learning (AutoML)
      approaches provide exciting opportunity to guide feature selection in agnostic
      metabolic profiling endeavors, where potentially thousands of independent data
      points must be evaluated. In previous research, AutoML using high-dimensional
      data of varying types has been demonstrably robust, outperforming traditional
      approaches. However, considerations for application in clinical metabolic
      profiling remain to be evaluated. Particularly, regarding the robustness of
      AutoML to identify and adjust for common clinical confounders. In this study, we
      present a focused case study regarding AutoML considerations for using the Tree
      Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in
      a biobank cohort. First, we propose a tandem rank-accuracy measure to guide
      agnostic feature selection and corresponding threshold determination in clinical
      metabolic profiling endeavors. Second, while AutoML, using default parameters,
      demonstrated potential to lack sensitivity to low-effect confounding clinical
      covariates, we demonstrated residual training and adjustment of metabolite
      features as an easily applicable approach to ensure AutoML adjustment for
      potential confounding characteristics. Finally, we present increased homocysteine
      with long-term exposure to metformin as a potentially novel, non-replicated
      metabolite association suggested by TPOT; an association not identified in
      parallel clinical metabolic profiling endeavors. While warranting independent
      replication, our tandem rank-accuracy measure suggests homocysteine to be the
      metabolite feature with largest effect, and corresponding priority for further
      translational clinical research. Residual training and adjustment for a potential
      confounding effect by BMI only slightly modified the suggested association.
      Increased homocysteine is thought to be associated with vitamin B12 deficiency -
      evaluation for potential clinical relevance is suggested. While considerations
      for clinical metabolic profiling are recommended, including adjustment approaches
      for clinical confounders, AutoML presents an exciting tool to enhance clinical
      metabolic profiling and advance translational research endeavors.

PMID- 29218906
TI  - Addressing vital sign alarm fatigue using personalized alarm thresholds.
AB  - Alarm fatigue, a condition in which clinical staff become desensitized to alarms
      due to the high frequency of unnecessary alarms, is a major patient safety
      concern. Alarm fatigue is particularly prevalent in the pediatric setting, due to
      the high level of variation in vital signs with patient age. Existing studies
      have shown that the current default pediatric vital sign alarm thresholds are
      inappropriate, and lead to a larger than necessary alarm load. This study
      leverages a large database containing over 190 patient-years of heart rate data
      to accurately identify the 1st and 99th percentiles of an individual's heart rate
      on their first day of vital sign monitoring. These percentiles are then used as
      personalized vital sign thresholds, which are evaluated by comparing to non
      default alarm thresholds used in practice, and by using the presence of major
      clinical events to infer alarm labels. Using the proposed personalized thresholds
      would decrease low and high heart rate alarms by up to 50% and 44% respectively,
      while maintaining sensitivity of 62% and increasing specificity to 49%. The
      proposed personalized vital sign alarm thresholds will reduce alarm fatigue, thus
      contributing to improved patient outcomes, shorter hospital stays, and reduced
      hospital costs.

PMID- 29218904
TI  - Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene
      expression.
AB  - Genome-wide association studies (GWAS) have been successful in facilitating the
      understanding of genetic architecture behind human diseases, but this approach
      faces many challenges. To identify disease-related loci with modest to weak
      effect size, GWAS requires very large sample sizes, which can be computational
      burdensome. In addition, the interpretation of discovered associations remains
      difficult. PrediXcan was developed to help address these issues. With built in
      SNP-expression models, PrediXcan is able to predict the expression of genes that
      are regulated by putative expression quantitative trait loci (eQTLs), and these
      predicted expression levels can then be used to perform gene-based association
      studies. This approach reduces the multiple testing burden from millions of
      variants down to several thousand genes. But most importantly, the identified
      associations can reveal the genes that are under regulation of eQTLs and
      consequently involved in disease pathogenesis. In this study, two of the most
      practical functions of PrediXcan were tested: 1) predicting gene expression, and
      2) prioritizing GWAS results. We tested the prediction accuracy of PrediXcan by
      comparing the predicted and observed gene expression levels, and also looked into
      some potential influential factors and a filter criterion with the aim of
      improving PrediXcan performance. As for GWAS prioritization, predicted gene
      expression levels were used to obtain gene-trait associations, and background
      regions of significant associations were examined to decrease the likelihood of
      false positives. Our results showed that 1) PrediXcan predicted gene expression
      levels accurately for some but not all genes; 2) including more putative eQTLs
      into prediction did not improve the prediction accuracy; and 3) integrating
      predicted gene expression levels from the two PrediXcan whole blood models did
      not eliminate false positives. Still, PrediXcan was able to prioritize GWAS
      associations that were below the genome-wide significance threshold in GWAS,
      while retaining GWAS significant results. This study suggests several ways to
      consider PrediXcan's performance that will be of value to eQTL and complex human
      disease research.

PMID- 29218907
TI  - Emergence of pathway-level composite biomarkers from converging gene set signals
      of heterogeneous transcriptomic responses.
AB  - Recent precision medicine initiatives have led to the expectation of improved
      clinical decisionmaking anchored in genomic data science. However, over the last
      decade, only a handful of new single-gene product biomarkers have been translated
      to clinical practice (FDA approved) in spite of considerable discovery efforts
      deployed and a plethora of transcriptomes available in the Gene Expression
      Omnibus. With this modest outcome of current approaches in mind, we developed a
      pilot simulation study to demonstrate the untapped benefits of developing disease
      detection methods for cases where the true signal lies at the pathway level, even
      if the pathway's gene expression alterations may be heterogeneous across
      patients. In other words, we relaxed the crosspatient homogeneity assumption from
      the transcript level (cohort assumptions of deregulated gene expression) to the
      pathway level (assumptions of deregulated pathway expression). Furthermore, we
      have expanded previous single-subject (SS) methods into cohort analyses to
      illustrate the benefit of accounting for an individual's variability in cohort
      scenarios. We compare SS and cohort-based (CB) techniques under 54 distinct
      scenarios, each with 1,000 simulations, to demonstrate that the emergence of a
      pathway-level signal occurs through the summative effect of its altered gene
      expression, heterogeneous across patients. Studied variables include pathway gene
      set size, fraction of expressed gene responsive within gene set, fraction of
      expressed gene responsive up- vs down-regulated, and cohort size. We demonstrated
      that our SS approach was uniquely suited to detect signals in heterogeneous
      populations in which individuals have varying levels of baseline risks that are
      simultaneously confounded by patient-specific "genome -by-environment"
      interactions (G*E). Area under the precision-recall curve of the SS approach far
      surpassed that of the CB (1st quartile, median, 3rd quartile: SS = 0.94, 0.96,
      0.99; CB= 0.50, 0.52, 0.65). We conclude that single-subject pathway detection
      methods are uniquely suited for consistently detecting pathway dysregulation by
      the inclusion of a patient's individual variability.
      http://www.lussiergroup.org/publications/PathwayMarker/.

PMID- 29218908
TI  - Analyzing metabolomics data for association with genotypes using two-component
      Gaussian mixture distributions.
AB  - Standard approaches to evaluate the impact of single nucleotide polymorphisms
      (SNP) on quantitative phenotypes use linear models. However, these normal-based
      approaches may not optimally model phenotypes which are better represented by
      Gaussian mixture distributions (e.g., some metabolomics data). We develop a
      likelihood ratio test on the mixing proportions of two-component Gaussian mixture
      distributions and consider more restrictive models to increase power in light of
      a priori biological knowledge. Data were simulated to validate the improved power
      of the likelihood ratio test and the restricted likelihood ratio test over a
      linear model and a log transformed linear model. Then, using real data from the
      Framingham Heart Study, we analyzed 20,315 SNPs on chromosome 11, demonstrating
      that the proposed likelihood ratio test identifies SNPs well known to participate
      in the desaturation of certain fatty acids. Our study both validates the approach
      of increasing power by using the likelihood ratio test that leverages Gaussian
      mixture models, and creates a model with improved sensitivity and
      interpretability.

PMID- 29218909
TI  - Reading Between the Genes: Computational Models to Discover Function from
      Noncoding DNA.
AB  - Noncoding DNA - once called "junk" has revealed itself to be full of function.
      Technology development has allowed researchers to gather genome-scale data
      pointing towards complex regulatory regions, expression and function of noncoding
      RNA genes, and conserved elements. Variation in these regions has been tied to
      variation in biological function and human disease. This PSB session tackles the
      problem of handling, analyzing and interpreting the data relating to variation in
      and interactions between noncoding regions through computational biology. We
      feature an invited speaker to how variation in transcription factor coding
      sequences impacts on sequence preference, along with submitted papers that span
      graph based methods, integrative analyses, machine learning, and dimension
      reduction to explore questions of basic biology, cancer, diabetes, and clinical
      relevance.

PMID- 29218910
TI  - Pan-cancer analysis of expressed somatic nucleotide variants in long intergenic
      non-coding RNA.
AB  - Long intergenic non-coding RNAs have been shown to play important roles in
      cancer. However, because lincRNAs are a relatively new class of RNAs compared to
      protein-coding mRNAs, the mutational landscape of lincRNAs has not been as
      extensively studied. Here we characterize expressed somatic nucleotide variants
      within lincRNAs using 12 cancer RNA-Seq datasets in TCGA. We build machine
      learning models to discriminate somatic variants from germline variants within
      lincRNA regions (AUC 0.987). We build another model to differentiate lincRNA
      somatic mutations from background regions (AUC 0.72) and find several molecular
      features that are strongly associated with lincRNA mutations, including copy
      number variation, conservation, substitution type and histone marker features.

PMID- 29218911
TI  - Convergent downstream candidate mechanisms of independent intergenic
      polymorphisms between co-classified diseases implicate epistasis among noncoding
      elements.
AB  - Eighty percent of DNA outside protein coding regions was shown biochemically
      functional by the ENCODE project, enabling studies of their interactions. Studies
      have since explored how convergent downstream mechanisms arise from independent
      genetic risks of one complex disease. However, the cross-talk and epistasis
      between intergenic risks associated with distinct complex diseases have not been
      comprehensively characterized. Our recent integrative genomic analysis unveiled
      downstream biological effectors of disease-specific polymorphisms buried in
      intergenic regions, and we then validated their genetic synergy and antagonism in
      distinct GWAS. We extend this approach to characterize convergent downstream
      candidate mechanisms of distinct intergenic SNPs across distinct diseases within
      the same clinical classification. We construct a multipartite network consisting
      of 467 diseases organized in 15 classes, 2,358 disease-associated SNPs, 6,301
      SNPassociated mRNAs by eQTL, and mRNA annotations to 4,538 Gene Ontology
      mechanisms. Functional similarity between two SNPs (similar SNP pairs) is imputed
      using a nested information theoretic distance model for which p-values are
      assigned by conservative scale-free permutation of network edges without
      replacement (node degrees constant). At FDR<=5%, we prioritized 3,870 intergenic
      SNP pairs associated, among which 755 are associated with distinct diseases
      sharing the same disease class, implicating 167 intergenic SNPs, 14 classes, 230
      mRNAs, and 134 GO terms. Co-classified SNP pairs were more likely to be
      prioritized as compared to those of distinct classes confirming a noncoding
      genetic underpinning to clinical classification (odds ratio ~3.8; p<=10-25). The
      prioritized pairs were also enriched in regions bound to the same/interacting
      transcription factors and/or interacting in long-range chromatin interactions
      suggestive of epistasis (odds ratio ~ 2,500; p<=10-25). This prioritized network
      implicates complex epistasis between intergenic polymorphisms of co-classified
      diseases and offers a roadmap for a novel therapeutic paradigm: repositioning
      medications that target proteins within downstream mechanisms of intergenic
      disease-associated SNPs. Supplementary information and software:
      http://lussiergroup.org/publications/disease_class.

PMID- 29218912
TI  - Network analysis of pseudogene-gene relationships: from pseudogene evolution to
      their functional potentials.
AB  - Pseudogenes are fossil relatives of genes. Pseudogenes have long been thought of
      as "junk DNAs", since they do not code proteins in normal tissues. Although most
      of the human pseudogenes do not have noticeable functions, ~20% of them exhibit
      transcriptional activity. There has been evidence showing that some pseudogenes
      adopted functions as lncRNAs and work as regulators of gene expression.
      Furthermore, pseudogenes can even be "reactivated" in some conditions, such as
      cancer initiation. Some pseudogenes are transcribed in specific cancer types, and
      some are even translated into proteins as observed in several cancer cell lines.
      All the above have shown that pseudogenes could have functional roles or
      potentials in the genome. Evaluating the relationships between pseudogenes and
      their gene counterparts could help us reveal the evolutionary path of pseudogenes
      and associate pseudogenes with functional potentials. It also provides an insight
      into the regulatory networks involving pseudogenes with transcriptional and even
      translational activities.In this study, we develop a novel approach integrating
      graph analysis, sequence alignment and functional analysis to evaluate pseudogene
      gene relationships, and apply it to human gene homologs and pseudogenes. We
      generated a comprehensive set of 445 pseudogene-gene (PGG) families from the
      original 3,281 gene families (13.56%). Of these 438 (98.4% PGG, 13.3% total) were
      non-trivial (containing more than one pseudogene). Each PGG family contains
      multiple genes and pseudogenes with high sequence similarity. For each family, we
      generate a sequence alignment network and phylogenetic trees recapitulating the
      evolutionary paths. We find evidence supporting the evolution history of
      olfactory family (both genes and pseudogenes) in human, which also supports the
      validity of our analysis method. Next, we evaluate these networks in respect to
      the gene ontology from which we identify functions enriched in these pseudogene
      gene families and infer functional impact of pseudogenes involved in the
      networks. This demonstrates the application of our PGG network database in the
      study of pseudogene function in disease context.

PMID- 29218914
TI  - Advances in Text Mining and Visualization for Precision Medicine.
AB  - According to the National Institutes of Health (NIH), precision medicine is "an
      emerging approach for disease treatment and prevention that takes into account
      individual variability in genes, environment, and lifestyle for each person."
      Although the text mining community has explored this realm for some years, the
      official endorsement and funding launched in 2015 with the Precision Medicine
      Initiative are beginning to bear fruit. This session sought to elicit
      participation of researchers with strong background in text mining and/or
      visualization who are actively collaborating with bench scientists and clinicians
      for the deployment of integrative approaches in precision medicine that could
      impact scientific discovery and advance the vision of precision medicine as a
      universal, accessible approach at the point of care.

PMID- 29218913
TI  - Leveraging putative enhancer-promoter interactions to investigate two-way
      epistasis in Type 2 Diabetes GWAS.
AB  - We utilized evidence for enhancer-promoter interactions from functional genomics
      data in order to build biological filters to narrow down the search space for two
      way Single Nucleotide Polymorphism (SNP) interactions in Type 2 Diabetes (T2D)
      Genome Wide Association Studies (GWAS). This has led us to the identification of
      a reproducible statistically significant SNP pair associated with T2D. As more
      functional genomics data are being generated that can help identify potentially
      interacting enhancer-promoter pairs in larger collection of tissues/cells, this
      approach has implications for investigation of epistasis from GWAS in general.

PMID- 29218915
TI  - Improving precision in concept normalization.
AB  - Most natural language processing applications exhibit a trade-off between
      precision and recall. In some use cases for natural language processing, there
      are reasons to prefer to tilt that trade-off toward high precision. Relying on
      the Zipfian distribution of false positive results, we describe a strategy for
      increasing precision, using a variety of both pre-processing and post-processing
      methods. They draw on both knowledge-based and frequentist approaches to modeling
      language. Based on an existing high-performance biomedical concept recognition
      pipeline and a previously published manually annotated corpus, we apply this
      hybrid rationalist/empiricist strategy to concept normalization for eight
      different ontologies. Which approaches did and did not improve precision varied
      widely between the ontologies.

PMID- 29218916
TI  - VisAGE: Integrating external knowledge into electronic medical record
      visualization.
AB  - In this paper, we present VisAGE, a method that visualizes electronic medical
      records (EMRs) in a low-dimensional space. Effective visualization of new
      patients allows doctors to view similar, previously treated patients and to
      identify the new patients' disease subtypes, reducing the chance of misdiagnosis.
      However, EMRs are typically incomplete or fragmented, resulting in patients who
      are missing many available features being placed near unrelated patients in the
      visualized space. VisAGE integrates several external data sources to enrich EMR
      databases to solve this issue. We evaluated VisAGE on a dataset of Parkinson's
      disease patients. We qualitatively and quantitatively show that VisAGE can more
      effectively cluster patients, which allows doctors to better discover patient
      subtypes and thus improve patient care.

PMID- 29218917
TI  - GeneDive: A gene interaction search and visualization tool to facilitate
      precision medicine.
AB  - Obtaining relevant information about gene interactions is critical for
      understanding disease processes and treatment. With the rise in text mining
      approaches, the volume of such biomedical data is rapidly increasing, thereby
      creating a new problem for the users of this data: information overload. A tool
      for efficient querying and visualization of biomedical data that helps
      researchers understand the underlying biological mechanisms for diseases and drug
      responses, and ultimately helps patients, is sorely needed. To this end we have
      developed GeneDive, a web-based information retrieval, filtering, and
      visualization tool for large volumes of gene interaction data. GeneDive offers
      various features and modalities that guide the user through the search process to
      efficiently reach the information of their interest. GeneDive currently processes
      over three million gene-gene interactions with response times within a few
      seconds. For over half of the curated gene sets sourced from four prominent
      databases, more than 80% of the gene set members are recovered by GeneDive. In
      the near future, GeneDive will seamlessly accommodate other interaction types,
      such as gene-drug and gene-disease interactions, thus enabling full exploration
      of topics such as precision medicine. The GeneDive application and information
      about its underlying system architecture are available at
      http://www.genedive.net.

PMID- 29218918
TI  - Annotating gene sets by mining large literature collections with protein
      networks.
AB  - Analysis of patient genomes and transcriptomes routinely recognizes new gene sets
      associated with human disease. Here we present an integrative natural language
      processing system which infers common functions for a gene set through automatic
      mining of the scientific literature with biological networks. This system links
      genes with associated literature phrases and combines these links with protein
      interactions in a single heterogeneous network. Multiscale functional annotations
      are inferred based on network distances between phrases and genes and then
      visualized as an ontology of biological concepts. To evaluate this system, we
      predict functions for gene sets representing known pathways and find that our
      approach achieves substantial improvement over the conventional text-mining
      baseline method. Moreover, our system discovers novel annotations for gene sets
      or pathways without previously known functions. Two case studies demonstrate how
      the system is used in discovery of new cancer-related pathways with ontological
      annotations.

PMID- 29218919
TI  - The diversity and disparity in biomedical informatics (DDBI) workshop.
AB  - The Diversity and Disparity in Biomedical Informatics (DDBI) workshop will be
      focused on complementary and critical issues concerned with enhancing diversity
      in the informatics workforce as well as diversity in patient cohorts. According
      to the National Institute of Minority Health and Health Disparities (NIMHD) at
      the NIH, diversity refers to the inclusion of the following traditionally
      underrepresented groups: African Americans/Blacks, Asians (>30 countries),
      American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander,
      Latino or Hispanic (20 countries). Gender, culture, and socioeconomic status are
      also important dimensions of diversity, which may define some underrepresented
      groups. The under-representation of specific groups in both the biomedical
      informatics workforce as well as in the patient-derived data that is being used
      for research purposes has contributed to an ongoing disparity; these groups have
      not experienced equity in contributing to or benefiting from advancements in
      informatics research. This workshop will highlight innovative efforts to increase
      the pool of minority informaticians and discuss examples of informatics research
      that addresses the health concerns that impact minority populations. This
      workshop topics will provide insight into overcoming pipeline issues in the
      development of minority informaticians while emphasizing the importance of
      minority participation in health related research. The DDBI workshop will occur
      in two parts. Part I will discuss specific minority health & health disparities
      research topics and Part II will cover discussions related to overcoming pipeline
      issues in the training of minority informaticians.

PMID- 29218920
TI  - INTEGRATING COMMUNITY-LEVEL DATA RESOURCES FOR PRECISION MEDICINE RESEARCH.
AB  - Precision Medicine focuses on collecting and using individual-level data to
      improve healthcare outcomes. To date, research efforts have been motivated by
      molecular-scale measurements, such as incorporating genomic data into clinical
      use. In many cases however, environmental, social, and economic factors are much
      more predictive of health outcomes, yet are not systematically used in clinical
      practice due to the difficulties in measurement and quantification. Advances in
      both the availability of electronic health information, environmental exposure
      data, and the more systematic use of geo-coding now provide ways to
      systematically assess community-level indicators of health, and link these
      factors to electronic health records for evaluating their influence on disease
      outcomes. In this workshop, we discuss new electronic sources of community-level
      data, and provide insight into their utility and validity when compared with gold
      standard data collection approaches.

PMID- 29218921
TI  - Machine learning and deep analytics for biocomputing: call for better
      explainability.
AB  - The goals of this workshop are to discuss challenges in explainability of current
      Machine Leaning and Deep Analytics (MLDA) used in biocomputing and to start the
      discussion on ways to improve it. We define explainability in MLDA as easy to use
      information explaining why and how the MLDA approach made its decisions. We
      believe that much greater effort is needed to address the issue of MLDA
      explainability because of: 1) the ever increasing use and dependence on MLDA in
      biocomputing including the need for increased adoption by non-MLD experts; 2) the
      diversity, complexity and scale of biocomputing data and MLDA algorithms; 3) the
      emerging importance of MLDA-based decisions in patient care, in daily research,
      as well as in the development of new costly medical procedures and drugs. This
      workshop aims to: a) analyze and challenge the current level of explainability of
      MLDA methods and practices in biocomputing; b) explore benefits of improvements
      in this area; and c) provide useful and practical guidance to the biocomputing
      community on how to address these challenges and how to develop improvements. The
      workshop format is designed to encourage a lively discussion with panelists to
      first motivate and understand the problem and then to define next steps and
      solutions needed to improve MLDA explainability.

PMID- 29218922
TI  - Methods for examining data quality in healthcare integrated data repositories.
AB  - This paper summarizes content of the workshop focused on data quality. The first
      speaker (VH) described data quality infrastructure and data quality evaluation
      methods currently in place within the Observational Data Science and Informatics
      (OHDSI) consortium. The speaker described in detail a data quality tool called
      Achilles Heel and latest development for extending this tool. Interim results of
      an ongoing Data Quality study within the OHDSI consortium were also presented.
      The second speaker (MK) described lessons learned and new data quality checks
      developed by the PEDsNet pediatric research network. The last two speakers (JB,
      RG) described tools developed by the Sentinel Initiative and University of Utah's
      service oriented framework. The workshop discussed at the end and throughout how
      data quality assessment can be advanced by combining best features of each
      network.

PMID- 29218924
TI  - Au/NiFe/M(Au, MoS2, graphene) trilayer magnetoplasmonics DNA-hybridized sensors
      with high record of sensitivity.
AB  - The demonstration of biosensors based on the surface plasmon effect holds promise
      for future high-sensitive electrodeless biodetection. The combination of magnetic
      effects with surface plasmon waves brings additional freedom to improve
      sensitivity and signal selectivity. Stacking biosensors with two-dimensional (2
      D) materials, e.g., graphene (Gr) and MoS2, can influence plasmon waves and
      facilitate surface physiochemical properties as additional versatility aspects.
      We demonstrate magnetoplasmonic biosensors through the detuning of surface
      plasmon oscillation modes affected by magnetic effect via the presence of the
      NiFe (Py) layer and different light absorbers of Gr, MoS2, and Au ultrathin
      layers in three stacks of Au/Py/M(MoS2, Gr, Au) trilayers. We found minimum
      reflection, resonance angle shift, and transverse magneto-optical Kerr effect
      (TMOKE) responses of all sensors in the presence of the ss-DNA monolayer. Very
      few changes of ~5*10-7 in the ss-DNA's refractive index result in valuable TMOKE
      response. We found that the presence of three-layer Gr and two-layer MoS2 on top
      of the Au/Py bilayer can dramatically increase the sensitivity by nine and four
      times, respectively, than the conventional Au/Co/Au trilayer. Our results show
      the highest reported DNA sensitivity based on the coupling of light with 2-D
      materials in magnetoplasmonic devices.

PMID- 29218923
TI  - Visible-light optical coherence tomography: a review.
AB  - Visible-light optical coherence tomography (vis-OCT) is an emerging imaging
      modality, providing new capabilities in both anatomical and functional imaging of
      biological tissue. It relies on visible light illumination, whereas most
      commercial and investigational OCTs use near-infrared light. As a result, vis-OCT
      requires different considerations in engineering design and implementation but
      brings unique potential benefits to both fundamental research and clinical care
      of several diseases. Here, we intend to provide a summary of the development of
      vis-OCT and its demonstrated applications. We also provide perspectives on future
      technology improvement and applications.

PMID- 29218926
TI  - [Determination of eight steroidal saponins in 15 kinds of genus Paris].
AB  - The study was established an HPLC method for simultaneous determination of 8
      steroidal saponins (polyphyllins VII, H, VI, II, I, and V, dioscin, and
      gracillin) in Paridis Rhizoma, and made an evaluation by determining steroidal
      saponins in 15 kinds of genus Paris. The analysis was performed on a Waters
      Acquity H-ClassTM UPLC ultrafine liquid chromatography system coupled with a PDA
      detector. The chromatographic separation was achieved through a CAPCELL PAK ADME
      (4.6 mm* 250 mm, 5 MUm) column and the optimal mobile phase consisted of
      acetonitrile and water. The column was maintained at 21 C, and the flow rate was
      0.8 mL*min -1. The UV detection wavelength was 203 nm. The results showed that 1
      the detected components can be well separated and all with good correlation
      coefficients. The standard calibration curves were linearly good (R2>0.999 9).
      The linearity was obtained over 0.041 70-3.812 00 MUg. The average recoveries
      ranged from 95.91% to 103.8%. 2 there are significant differences in the content
      of steroidal saponins from different species. The steroidal saponins are low
      content or almost none in P. mairei, P. polyphylla var. stenophylla, and P.
      delavayi have low content or almost did not contain, so these species are not
      suitable for medicinal use. The contents of steroidal saponins in P. polyphylla
      var. chinensis are varied from different places. There were high content of
      steroidal saponins in P. polyphylla var. yunnanensis, P. forrestii, P. daliensis,
      and P. axialis, even up to 5.0%, which indicated that they had the potential
      pharmic value of development.

PMID- 29218925
TI  - [Exploring the clinical characters of Shugan Jieyu capsule through text mining].
AB  - In this paper,the potential climate factors affecting the Pairs polyphylla var.
      yunnanensis distribution in China at rational scales were selected from related
      literatures, using the sampling point geographic information from of P.
      polyphylla var. yunnanensis, combine the maximum entropy model (MaxEnt) with
      spatial analyst function of ArcGIS software, to study the climate suitability of
      P. polyphylla var. yunnanensis cultivating region in China and the leading
      climate factors. The results showed that, average rainfall in August, average
      rainfall in October, coefficient of variation of seasonal precipitation, the
      average temperature of the dry season, isothermal characteristic, average
      temperature in July were the leading climate factors affecting the potential
      distribution of P. polyphylla var. yunnanensis cultivating region in China, with
      their cumulative contribution rate reached 97.2% of all candidate climate
      factors. Existence probability of the region to be predicted of P. polyphylla
      var. yunnanensis through the constructed model, the climate unsuitable region,
      low, medium and high region of P. polyphylla var. yunnanensis in China were
      clarified and the threshold of climatic factors were gave and clarified the
      climate characteristics of the cultivating region in each climatic suitability
      division. The results of research can provide reference for production layout and
      introduction of P. polyphylla var. yunnanensis.

PMID- 29218927
TI  - [Qualitative and quantitative analyses of primary saponins in Paris forrestii].
AB  - In order to study whether Paris forrestii could be developed as a substitute of
      Paridis Rhizome, chemical compositions of P. forrestii and P. polyphylla var.
      yunnanensis were investigated by UPLC-Q-TOF MS. In addition, the contents of
      eight primary steroidal saponins in 77 batches of P. forrestii samples from
      different habitats were simultaneously determined by HPLC-UV. The results showed
      that P. forrestii and P. polyphylla var. yunnanensis have similar chemical
      compositions, and all 22 major common peaks were identified as steroid
      derivatives. Meanwhile, there were some differences in the contents of saponins
      in P. forrestii samples from different habitats. The contents of 4 steroidal
      saponins in Chinese Pharmacopoeia ranged from 0.068% to 3.30%, and the highest
      content of the 8 kinds of steroidal saponins was 6.18%, while the lowest was just
      0.71%. Moreover, 78% of P. forrestii samples were in conformity with the
      requirements of Chinese Pharmacopoeia, indicating that P. forrestii samples had
      relatively stable quality and could be further studied as a substitute for
      Paridis Rhizome.

PMID- 29218928
TI  - [Comparative pharmacodynamics study on Paris forrestii and pharmacopoeial Paridis
      Rhizoma].
AB  - Paris is a raw material of a variety of Chinese medicines, which has become
      deficient in resource due to market demand substantial growth and wild Paris
      resources reducing increasingly and the artificial cultivation slow growth. This
      study compared pharmacological activity in analgesia and anti-inflammatory and
      hemostasis effects of P. forrestii with pharmacopoeial Paridis Rhizoma to expand
      its range of Paris medicinal resources and protect wild resources of Paris and
      meet market demand. The experimental study showed that P. forrestii and P.
      polyphylla var. yunnanensis and P. polyphylla var. chinensis had analgesic, anti
      inflammatory and hemostatic effects. They can significantly reduce the number of
      writhing and inhibit rat foot swelling induced by carrageenan and mice capillary
      permeability induced by acetic acid and short the bleeding time and clotting
      time. Their function is equivalent.

PMID- 29218929
TI  - [Pharmacodynamics study on Paris vietnamensis].
AB  - Paris is commonly used in traditional Chinese medicine and its resource is in
      shortage, a variety of related plants are acquired as Paris. This study compared
      pharmacological activity in anti-inflammatory and hemostatic and blood rheology
      of P. vietnamensis with pharmacopoeial Paridis Rhizoma to expand its range of
      Paris medicinal resources and protect wild resources of Paris and meet market
      demand. The experimental study showed that P. vietnamensis and P. polyphylla var.
      yunnanensis and P. polyphylla var. chinensis had anti-inflammatory and hemostatic
      effect and improved blood rheolog. They can significantly inhibit rat foot
      swelling induced by carrageenan and short the bleeding time and clotting time and
      reduce the blood viscosity in rats with acute blood stasis model, P. vietnamensis
      and P. polyphylla var. yunnanensis can inhibit mice capillary permeability
      induced by acetic acid.

PMID- 29218930
TI  - [Herbal textual research on origins of Chonglou].
AB  - Based on the field investigation, this paper researched the germplasms and
      geoherbs habitat of Chonglou in ancient herbal books systematically. The results
      showed that, Chonglou in ancient herbal books sometimes referred to certain
      specific germplasm, while sometimes it referred to many species derived from
      genus Paris except Sect. Paris. The medicinal material Chonglou in Chinese
      Materia Medica Bencaotujing and Bencaomengquan was verified as P. polyphylla var.
      chinensis, which could be P. polyphylla in Xinxiubencao, and it should include P.
      polyphylla or P. polyphylla var. stenophylla in Bencaogangmu. However, it proved
      to be a variety of species from Paris that can used as Chonglou in Diannanbencao
      and Zhiwumingshitukao. Moreover, the origins of Chonglou were correspondingly
      more diverse, with its producing areas changed from North to South. Therefore,
      with the resources increasing endangered, the botanical origin of Chonglou should
      be further studied.

PMID- 29218931
TI  - [Research progress in phytoestrogens of traditional Chinese medicine].
AB  - Phytoestrogens are plant-derived compounds, which have a similarity in structure
      with human endogenous estrogen 17-beta-estradiol. Structural likeness enables
      phytoestrogens to interact with estrogen receptors, not simply mimicking the
      effects of human steroidal estrogen but also exhibiting similar and divergent
      actions. The global literature relating to phytoestrogen in recent years was
      systematically summarized in this paper. Chemical compositions of phytoestrogens
      were mainly flavonoids, coumarins, lignans, terpenoids, steroids, etc., with a
      character of prevention and treatment of perimenopausal syndrome, osteoporosis,
      cardiovascular disease, metabolic diseases, cancer, regulation of brain function
      and other pharmacological effects. The mechanisms of action mainly included
      classical estrogen receptor pathway, epigenetic effect, activation of 5'-adenosyl
      phospho-activated protein kinase, inhibition of kinase, activation of peroxisome
      proliferator-activated receptor, regulation of apoptosis-related proteins,
      inhibition of nuclear factor kappaB signaling pathway and so on. According to
      their efficacy classification, phytoestrogens were mainly distributed in the
      tonifying medicines, blood-activating and stasis-resolving medicines and heat
      clearing medicines. The classical prescriptions with estrogen activity included
      tonifying formula, Qi-regulating formula and harmonizing formula, etc. This
      review was aimed at providing a certain reference for the further study of
      phytoestrogens by researchers and clinicians.

PMID- 29218932
TI  - [Research progress of Bixie].
AB  - The Dioscorea hypoglauca rhizome and D. spongiosa rhizome in "China
      Pharmacopoeia" are often used as Bixie in clinically, with the function of
      removing dampness, clearing away turbidness and dispelling wind to remove pain,
      and has been widely used in stranguria marked by chyluria, joint stiffness and
      rheumatic arthralgia. It has obvious curative effect and broad application
      prospect. However, in recent years the progress of research is slow for its
      miscellaneous sources, chaotic varieties and lack of relevant quality assessment.
      The previous research on Bixie is mainly reflected in the chemical compositions,
      mainly including steroids, diarylheptanoids and lignans and so on. Among them,
      steroidal saponins are the main components and the main effective substances for
      their pharmacological activities. Recent studies have shown that Bixie and its
      main components have significant effects in anti-trioxypurine, anti-inflammation,
      analgesia and anti-osteoporosis, and have made great progress, providing an
      experimental basis for the research and development of clinical drugs. But the
      specific substance and specific mechanism of its pharmacological action are not
      clear, and need further exploration. By consulting the relevant literature at
      home and abroad, the author has summarized the chemical constituents, quality
      evaluation, pharmacological action of Bixie, hoping to provide a reference for
      further research, development and utilization of Bixie.

PMID- 29218933
TI  - [Research progress of Bixie].
AB  - The extract of ginkgo leaves showed positive effects on treatments of many
      diseases, and has been used clinically worldwide. Considering the fact that
      flavonoids are the main bioactive components in the extract of ginkgo leaves, it
      is very important to investigate the flavonoid biosynthesis in ginkgo leaves. In
      this paper, we first reviewed the research progress of flavonoid biosynthesis in
      different plants, and introduced the flavonoid biosynthesis related genes
      discovered in ginkgo. Then, several cases of ginkgo researches using high
      throughput sequencing technology were described in detail. In addition, as an
      important research area in ginkgo, the changes of flavonoid content and the
      expression of corresponding genes were discussed. Specifically, our latest
      results were described. At last, we prospected the development of research area
      in flavonoid biosynthesis in ginkgo.

PMID- 29218934
TI  - [Quantative analysis of eupatilin and jaceosidin in folium of Artemisia argyi
      from different areas in China by RP-HPLC based on ancient medicine books].
AB  - In order to evaluate the quality of Artemisia argyi from Qichun, Ningbo, Anguo
      and Nanyang, the contents of eupatilin and jaceosidin were determined by RP-HPLC.
      The determination was performed on Agilent Eclipse XDB-C18 (4.6 mm*250 mm, 5 MUm)
      with mobile phase consisted of acetonitrile-0.2% phosphoric acid(35?65) at the
      flow rate 1.0 mL*min -1. The detection wavelength was 350 nm and the column
      temperature was 25 C. The results showed that the amount of eupatilin and
      jaceosidin had a clear linear relationship in the range of 0.003-0.126 g*L -1
      (r=0.999 9) and 0.005-0.200 g*L -1 (r=0.999 9), and the average recovery rates
      for them were 99.14% (n=6, RSD 1.2%) and 99.40% (n=6, RSD=0.73%), respectively.
      The results showed that RP-HPLC can be used for the quantification of eupatilin
      and jaceosidin in the folium of A. argyi. With this method, we found there was no
      significant difference of jaceosidin content within all the samples collected,
      but the content of eupatilin was significantly higher in samples from Qichun,
      Ningbo, Xiangyang and Nanyang, located in the south of Huaihe River compared with
      these from other areas.

PMID- 29218935
TI  - [Antifungal effects of three medicinal crops on Phytophthora nicotianae].
AB  - Tobacco black shank is one of the most harmful soil-borne diseases infected by
      Phytophthora parasitica. In order to probe the control method to this disease, in
      this study, the mycelial growth rate method was employed to investigate the
      antifungal effects of extracts from stem-leaf and root, root exudates, and their
      combination of Scrophularia ningpoensis, Chuanmingshen violaceum and Pinellia
      ternata The results showed that: 1Stem-leaf and root extracts of S. ningpoensis,
      C. violaceum and P. ternata exhibited different antifungal activities, and the
      inhibition increased with the increase of extract concentration. The antifungal
      effect of S. ningpoensis extracts at 0.5 g*mL-1 was the strongest than other
      medicinal plants, the inhibition rate of steam-leaf and root extracts reached
      74.88%, 69.27%, respectively. The inhibitory effect of C. violaceum and P.
      ternata was relatively lower, however, there is a significant gain effect after
      combination of steam-leaf and root extracts of C. violaceum. 2The root exudates
      of S. ningpoensis, C. violaceum and P. ternata showed fungistasis to Phytophthora
      nicotianae, and fungistasis was enhanced with the increase of root exudate
      concentration. The antifungal effect in the order of C. violaceum > S.
      ningpoensis > P. ternata. 3The antifungal activity of combination of extract and
      root exudate from S. ningpoensis was similar with the effect of C. violaceum,
      they were both stronger than P. ternata, and the antifungal activity for three
      combination were located between the antifungal activity of their extracts and
      root exudates. S. ningpoensis and C. violaceum can be potentially applied to
      prevent and control the tobacco black shank.

PMID- 29218936
TI  - [Comparative study on acute toxicity of different active ingredient fractions
      from Kansui stir-baked with vinegar on zebrafish embryos].
AB  - The 24 h normal developing zebrafish embryos were used to evaluate the acute
      toxicity and the compounds of respective fractions were analyzed by UFLC-Q-TOF-MS
      simultaneously. Nine concentration groups with respective concentration and a
      blank control group were designed for each fraction to investigate their effect
      on survival rates of zebrafish embryos 96 h after drug administration, and
      calculate the median lethal concentration (LC50) of different fractions to
      zebrafish embryos. The results showed that all of the fractions had acute
      toxicity to zebrafish embryos except VEKD, and the order was as follows: VEKB,
      VEKC, VEKA and VEKD. According to the results of UFLC-Q-TOF-MS, the chemical
      ingredients contained in VEKB and VEKC were mainly composed of ingenane-type and
      japhane-type diterpenoids, respectively. It could be speculated that japhane-type
      diterpenoids might be the active compounds with lower toxicity associated with
      the results of toxicity study, providing some references for the further research
      on effective material basis of Kansui stir-baked with vinegar according to the
      principle of "drastic medicine, no death risks".

PMID- 29218937
TI  - [Standard decoction of Leonuri Herba].
AB  - To build an evaluation standard for quality of Leonuri Herba standard decoction.
      13 batches of Leonuri Herba standard decoction with different quality were
      prepared. The contents of leonurine hydrochloride and stachydrine hydrochloride
      were determined; then the transfer rate and the extract rate were calculated and
      pH value was measured; and HPLC fingerprint method was established for analysis.
      The results of 13 batches of samples revealed that the transfer rate of leonurine
      hydrochloride and stachydrine hydrochloride was 30.0%-53.4% and 67.0%-82.6%,
      respectively; the extract rate was 12.1%-18.3% and the pH value was 5.87-6.22.
      Moreover, 12 common chromatographic peaks were determined based on fingerprint by
      using Similarity Evaluation System for Chromatographic fingerprint of Traditional
      Chinese Medicine (2012A). The similarity of 13 batches of samples was analyzed
      and compared, and the results showed that the similarity was higher than 0.9. In
      this study, the preparation method for Leonuri Herba decoction was standard, with
      high similarity in fingerprint, showing high precision, stability and
      repeatability in fingerprint analysis. Thus, this study can provide a reference
      for the quality control of Leonuri Herba dispensing granules.

PMID- 29218938
TI  - [Analysis of chemical markers in sulfur-fumigated Anemarrhenae Rhizoma].
AB  - Sulfur-containing Anemarrhenae Rhizoma decoction pieces were prepared by using
      sulfur-fumigating procedure. The difference components before and after sulfur
      fumigation in Anemarrhenae Rhizoma were analyzed and on-line identified by UPLC-Q
      TOF-MSE combined with UNIFI informatics platform, principal component analysis
      (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA)
      respectively. As a result, 16 major differences components were identified, and
      among them, 9 components were mainly from sulfur-fumigated samples. The main
      chemical markers in sulfur-fumigated Anemarrhenae Rhizoma were identified as the
      sulfite derivatives newly produced after sulfur-fumigating. Meanwhile, UPLC-Q-TOF
      MSE was used to find the main chemical marker anemarrhena saponin BII sulfite
      (m/z 983). By using this method, a rapid screening method for sulfur-fumigated
      Anemarrhenae Rhizoma was established. This was a convenient and accurate
      detection method for sulfur dioxide residue, and it can be used as an effective
      assistant method to control the quality of Anemarrhenae Rhizoma. At the same
      time, it was the first time to identify sulfited derivatives of steroidal
      saponins, and screen the sulfur-fumigated Anemarrhenae Rhizoma.

PMID- 29218940
TI  - [Studying on purification technology of Resina Draconis phenol extracts based on
      design space method].
AB  - The "design space" method was used to optimize the purification process of Resina
      Draconis phenol extracts by using the concept of "quality derived from design"
      (QbD). The content and transfer rate of laurin B and 7,4'-dihydroxyflavone and
      yield of extract were selected as the critical quality attributes (CQA). Plackett
      Burman design showed that the critical process parameters (CPP) were
      concentration of alkali, the amount of alkali and the temperature of alkali
      dissolution. Then the Box-Behnken design was used to establish the mathematical
      model between CQA and CPP. The variance analysis results showed that the P values
      of the five models were less than 0.05 and the mismatch values were all greater
      than 0.05, indicating that the model could well describe the relationship between
      CQA and CPP. Finally, the control limits of the above 5 indicators (content and
      transfer rate of laurine B and 7,4'-dihydroxyflavone, as well as the extract
      yield) were set, and then the probability-based design space was calculated by
      Monte Carlo simulation and verified. The results of the design space validation
      showed that the optimized purification method can ensure the stability of the
      Resina Draconis phenol extracts refining process, which would help to improve the
      quality uniformity between batches of phenol extracts and provide data support
      for production automation control.

PMID- 29218939
TI  - [Evaluate effects of different drying methods on quality of Tianshu capsule on
      substance basis].
AB  - To investigate the effect of hot air circulation drying and spray drying on the
      quality of Tianshu capsule from the view point of chemical compositions. UPLC-DAD
      was used to establish the fingerprint of Tianshu capsules for the first time, and
      the main chemical constituents were identified by UPLC-Q-TOF-MS/MS. A total of 62
      compounds were identified in this method, 21 of which were reported in Tianshu
      capsules for the first time. The results showed that there were no significant
      differences in the identification of the chemical constituents types between
      these two methods, but the contents of some constituents were different. The
      common patterns generated by the 10 batches of hot air cycle drying samples were
      used as the control fingerprint, and the similarity of the spray drying samples
      fingerprints was 0.877, with high similarity of the fingerprints between these
      two methods. UPLC-DAD combined with UPLC-Q-TOF-MS/MS technology was used for the
      first time to evaluate the chemical constituents of Tianshu capsule rapidly,
      comprehensively and accurately, providing technical support for the quality
      evaluation of Tianshu capsule.

PMID- 29218941
TI  - [Study on diarylheptanoids from green peel of Juglans sigillata].
AB  - The chemical constituents from green peel of Juglans sigillata were isolated by
      column chomatographies over silica gel, Sephadex LH-20, and MCI. Four
      diarylheptanoids were isolated and their structures were characterized as
      dihydropterocarine(1), 3',4"-epoxy-1-(4'-hydroxy-phenyl)-7-(3"-methoxyl-phenyl)
      heptan-3alpha-ol(2), pterocarine(3), and 1-(4'-hydroxy-phenyl)-7-(3"-methoxy-4"
      hydroxyphenyl)-heptan-3alpha-ol(4). Compound 1 is a new compound, named as
      dihydropterocarine. Compounds 2-4 were isolated from the plant of J. sigillata
      for the first time.

PMID- 29218942
TI  - [Analysis of alcohol extract and water extract of Polygonum capitatum by UPLC-Q
      TOF-MS].
AB  - In this study, we used Ultra Performance Liquid Chromatography-Time-of-Flight
      Mass Spectrometry(UPLC-TOF-MS)to identify the chemical constituents in both
      ethanol and water extract of Polygonum capitatum. A Waters ACQUITY UPLC BEH C18
      column(2.1 mm*100 mm,1.7 MUm) was used for separation. The mobile phase was
      consisted of(A) 0.10% formic acid in water and(B)0.10% formic acid in
      acetonitrile, and the flow rate was 0.35 mL*min-1. ESI source in negative ion
      mode was used for MS detection. Structural identification was carried out
      according to the accurate mass and matching with database. The results showed
      that flavonoids, polyphenols and lignans were the main components in both
      extracts. However, the chemical compositions of both extracts were different,
      e.g. there are less hydrolyzable tannins, loss of ellagic acid and more
      anthocyanins in ethanol extract. In a conclusion, this study provides an
      important scientific basis for identifying the active ingredients in P.
      capitatum, which also help to reveal the pharmacological effect of P. capitatum.

PMID- 29218943
TI  - [Effect of germacrone in alleviating HUVECs damaged by H2O2-induced oxidative
      stress].
AB  - This study focuses on the protective effect of germacrone on human umbilical vein
      endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its
      possible mechanisms. The oxidative damage model was established by using 500
      MUmol*L-1 H2O2 to treat HUVECs for 3 hours, and then protected with different
      concentrations of germacrone for 24 hours. The effect of germacrone on cell
      viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2,
      TXB2, ET-1, t-PA, PAI-1, TNF-alpha and IL-6 were detected by ELISA. The content
      of NO was detected by using nitrate reductase method. Colorimetry was used to
      detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST
      1 and microplate respectively. Apoptosis was observed by Hoechst 33258
      fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells
      were detected by RT-PCR. The results showed that the cell damage rate was 52%
      after treated with 500 MUmol*L-1 H2O2 for 3 hours. The cell activity was
      increasing with the rise of germacrone concentration within the range of 20-200
      mol*L-1. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD,
      GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The
      contents of PAI-1, ET-1, IL-6, TNF-alpha, TXB2, LDH, MDA, Bax mRNA and Caspase-3
      mRNA expressions were increased. Compared with model group, the contents of PGI2,
      NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after
      treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-alpha, TXB2, LDH,
      MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with
      germacrone. According to Hoechst 33258 fluorescence staining, compared with
      normal group, the cell membrane and the nucleus showed strong dense blue
      fluorescence, and the number of cells significantly decreased in model group.
      Compared with model group, blue fluorescence intensity decreased in drug group.
      The above findings demonstrate that germacrone may improve the effect on HUVECs
      damaged by H2O2-induced oxidative stress by resisting oxidation and inhibiting
      cell apoptosis.

PMID- 29218944
TI  - [Activity of essential oil extracted from Artemisia argyi in inducing apoptosis
      of Candida albicans].
AB  - To explore the activity of essential oil extracted from Artemisia argyi (AAEO) in
      inducing the apoptosis of Candida albicans SC5314. The effect of AAEO on reactive
      oxygen species(ROS) and mitochondria membrane potential(MMP) of C. albicans
      SC5314 was detected by flow cytometry. Phosphatidylserine externalization was
      observed under fluorescence microscopic with Annexin-V/PI staining at the early
      stage of apoptosis in C. albicans. Metacaspase activity was observed under
      fluorescence microscopic with FITC-VAD-FMK staining at the early stage of
      apoptosis in C. albicans. C. albicans morphology was observed by DAPI nuclear
      staining and fluorescence microscopy. After intervention with 0.5 mL*L-1 AAEO,
      apoptosis of C. albicans significantly increased, metacaspase activity increased,
      nuclear pyknosis and fragmentation, and intracellular ROS were significantly
      increased, and mitochondrial membrane potential decreased significantly. The
      certain concentrations of AAEO could induce the apoptosis of C. albicans.

PMID- 29218945
TI  - [Prediction of drug-target interaction based on fingerprint similarity].
AB  - Drugs play the pharmacological effects by combining with target proteins.
      Identification of drug-target interactions is important for discovering new
      functions of drugs. In this paper, the target fingerprints based on molecular
      substructure and the drug-target similarity based on fingerprints are proposed to
      a random forest-based classification method, in order to identify the drug-target
      interactions. Experiments on enzymes, ion channels, G protein-coupled receptors
      and nuclear receptors proved the effectiveness of the proposed method. In
      addition, the proposed method is applied to predict the interactions between
      ingredients and targets of traditional Chinese medicines.

PMID- 29218946
TI  - [Metabolism of Inula cappa extract by rat intestinal bacteria in vitro].
AB  - To investigate the metabolism of major components in Inula cappa by rat
      intestinal bacteria in vitro. I. cappa extract was incubated for 24 h with rat
      intestinal bacteria under anaerobic environment. After the samples were
      precipitated by n-butanol, UPLC-Q-TOF-MS/MS was applied for the qualitative
      analysis of the metabolites, combined with data software such as Metabolite
      Tools, Data Analysis and so on. The potential metabolites in rat intestinal
      bacteria were analyzed by comparing the total ion current of the test samples and
      blank samples and analyzing the quasi-molecular ion and fragment ion of all
      chromatograms. The results injected that fourteen metabolites were detected in
      rat intestinal flora. Various types of metabolic reactions happen to
      caffeoylquinic acid in intestinal flora, including isomerization, hydrolyzation,
      there were also methylation, hydrogenation and acetylation of caffeic acid. At
      the same time, a methylate of dicaffeoylquinic acid was also detected.
      Presumably, caffeoylquinic acids were gradually transformed into more hydrophobic
      metabolites with smaller molecular mass, which were better absorbed by the
      intestinal tract.

PMID- 29218947
TI  - [Study on mechanism of hepatotoxicity of Ploygoni Multiflori Caulis based on
      function inhibition of bilirubin-associated transporters in idiosyncratic rat].
AB  - To explore the possible mechanism of liver injury, the effects of Ploygoni
      Multiflori Caulis and its extractive on the function of bilirubin-associated
      transporters were investigated in normal (N) and idiosyncratic (LPS) rats (M).
      The normal and LPS rats were respectively administrated powder of Ploygoni
      Multiflori Caulis, its extractive and same volume of 0.5% CMC-Na solution for 7
      d. BSP, a substrate of the transporters of Oatp1a1 and Oatp1b2 was selected, and
      its pharmacokinetic parameters of intravenous injection were determined to
      examined the activity these transporters. Meanwhile the mRNA expressions of
      transporters were detected. Compared with N-blank control group, besides M-powder
      group, the Cmax has no significantly different from other groups, t1/2, AUC0-t
      and AUC0-infinity were significantly increased, and CL were significantly
      decreased. However, compared with N- blank control group, AST and ALT decreased
      significantly. The expression of Oatp1a1, Oatp1b2 and MRP2 mRNA was significantly
      decreased (P<0.05), but there was no act synergistically when Ploygoni Multiflori
      Caulis and extractive were combined with LPS. The function of Oatp1a1, Oatp1b2
      and MRP2 in rats were significantly inhibited by Ploygoni Multiflori Caulis and
      extractive, which may be an important cause of hepatotoxicity.

PMID- 29218948
TI  - [Preliminary screening of biomarkers for curcumin's antidepressant effect based
      on metabonomics method].
AB  - To screen potential biomarkers of curcumin related to treating depression rats by
      using metabolomics means, so as to explore the antidepressant action mechanism of
      curcumin. The healthy male SD rats were randomly divided into four groups.
      Chronic unpredictable mild stress (CUMS) stimulation was conducted for modeling
      for 2 weeks, and then curcumin (200 mg*kg-1) or venlafaxine (40 mg*kg-1) was
      given by gavage administration. The blank group and model group rats were given
      with the same volume of 1% CMCNa normal saline, once per day for two weeks. The
      rats serum for each group was collected and LC/MS-IT-TOF method was used to
      characterize the metabolic differences. Also multivariate statistical analysis
      was used to screen possible potential biomarkers and analyze the possible
      metabolic pathways. After administration of curcumin and venlafaxine
      respectively, the depression indexes of CUMS model rats were all improved
      significantly (P<0.05), but there were no significant differences between
      curcumin and venlafaxine groups. In PCA and PLS-DA analysis after curcumin or
      venlafaxine intervention on CUMS model group rats, the small molecule metabolites
      level reflects a normal trend, and particularly for the curcumin group. Through
      metabonomics technology, 11 biomarkers associated with curcumin antidepressant
      effect were screened, and at the same time seven metabolic pathways were
      involved. The results showed that curcumin had antidepressant effects, which was
      evident in both macro and micro levels, comparable with positive drug of
      venlafaxine. The antidepressant effect of curcumin may be associated with the
      glycerol phospholipid metabolism, linoleic acid metabolism, pentose and
      glucuronic acid ester and ether lipid metabolism, but still need further
      exploration in the future.

PMID- 29218949
TI  - [Study on relationship between constitution and syndrome of MMP-9, IL-6 and MTHFR
      gene in patients with ischemic stroke].
AB  - By studying the relationship between syndromes, physique and MMP-9, IL-6 and
      MTHFR gene polymorphisms in patients with ischemic stroke,The relationship
      between MMP-9, IL-6 and MTHFR gene polymorphism was analyzed in patients with
      ischemic stroke.The data were collected by collecting the data of patients with
      ischemic stroke, and the statistical analysis was carried out. Syndrome:61 cases
      of ischemic stroke patients with stroke phlegm stasis syndrome in patients with
      the highest frequency, a total of 30 cases; Physical constitution: phlegm is
      ischemic stroke patients prone to physical, a total of 20 cases; The analysis of
      the relationship between constitution and syndrome shows that the patients with
      qi deficiency constitution tend to show qi deficiency and blood stasis syndrome
      after onset, The analysis of the relationship between constitution and syndrome
      shows that the patients with qi deficiency constitution tend to show qi
      deficiency and blood stasis syndrome after onset, Phlegm constitution and
      physical condition after the onset of symptoms tend to wind phlegm stasis
      syndrome; Syndrome and MMP-9, IL-6 relationship:The distribution of MMP-9 and IL
      6 in patients with qi and phlegm stasis syndrome and qi deficiency and blood
      stasis syndrome was significantly different from that in Z test (P<0.05). The
      level of MMP-9 in patients with qi deficiency and blood stasis syndrome was
      significantly higher than that in patients with wind phlegm and blood stasis
      syndrome;The level of IL-6 in patients with phlegm and blood stasis syndrome was
      significantly higher than that in patients with qi deficiency and blood stasis
      syndrome. Syndrome, constitution and MTHFR gene polymorphism: among the 61
      samples, 34 were heterozygous mutations, 15 were pure and mutated, 12 had no
      mutation, The mutation rate of this locus was 4.08 times that of patients without
      mutations.The genotype of MTHFR C677T in patients with phlegm dampness tends to
      be CT genotype. Wind phlegm stasis syndrome in patients with easy to appear after
      the TT genotype; Yin deficiency syndrome in patients prone to miscellaneous and
      mutations, the performance of CT genotype; Analysis of the relationship between
      syndromes and physique in patients with ischemic stroke,Phlegm and dampness, flat
      quality patients after the onset of easy to show the wind phlegm stasis syndrome;
      Qi deficiency after the onset of symptoms in patients with Qi and blood stasis.
      Suggesting that before the onset of such as for the partial physical
      conditioning, may be on the prevention of ischemic stroke have a certain effect;
      Analysis of the relationship between syndromes and MMP-9 and IL-6 in patients
      with ischemic stroke, Wind phlegm stasis syndrome and IL-6 levels are related, Qi
      deficiency and blood stasis syndrome and MMP-9 levels are related. Analysis of
      the relationship between syndromes and MTHFR gene polymorphism in patients with
      ischemic stroke, TT genotype after the onset of symptoms prone to wind phlegm
      stasis syndrome, CT genotype patients after the onset of easy manifestations of
      Yin deficiency wind syndrome; Analysis of the relationship between physique and
      MTHFR gene polymorphism in patients with ischemic stroke, CT genotype is easy to
      show phlegm.For more in-depth understanding of pathogenesis of ischemic stroke to
      provide the basis, For the clinical treatment and prevention to provide
      intervention strategies.

PMID- 29218950
TI  - [Meta-analysis of Yiqi Huoxue method in treating idiopathic membranous
      nephropathy].
AB  - The incidence of idiopathic membranous nephropathy (IMN) is increasing year by
      year, and the clinical research on Chinese medicine treatment of INM is also
      growing. This study aims to evaluate the efficiency and safety of Yiqi Huoxue
      method for IMN. Data sources used were from PubMed, EMbase, the Cochrane Library,
      CBM, CNKI, Wanfang and VIP database. Two researchers independently screened the
      literature and extracted data. RevMan 5.3 software was used for Meta analysis,
      and the evidences were graded for the outcomes according to GRADE system by using
      GRADEprofiler 3.6. Eventually, eleven trials (725 participants) were included in
      the Meta-analyses. There was statistically significant difference between Yiqi
      Huoxue method and controls when combining all trials in 24 h UTP [RR=-1.23,
      95%CI=(-1.94,-0.53), P=0.000 6] or when combining all trials in ALB [RR=3.56,
      95%CI=(1.64, 5.47), P=0.000 3]. Meanwhile, there was statistically significant
      difference between Yiqi Huoxue method and controls when combining all trials in
      TC [RR=-0.39, 95%CI=(-0.57, -0.20), P<0.000 1] or when combining all trials in TG
      [RR=-0.49, 95%CI=(-0.82, -0.15), P=0.004]. However, there was no statistically
      significant difference between Yiqi Huoxue method and controls when combining all
      trials in Scr [RR=-3.25, 95%CI=(-9.35, 2.84), P=0.30] or when combining all
      trials in BUN [RR=-0.81,95%CI=(-2.29, 0.66), P=0.28]. In the statistics, the most
      frequently used Chinese medicines in clinical application were Astragali Radix,
      Angelicae Sinensis Radix, Chuanxiong Rhizoma, Codonopsis Radix, Atractylodis
      Macrocephalae Rhizome and Salvia Miltiorrhiza. The present evidences suggested
      that Yiqi Huoxue method should be thought highly of in the treatment of IMN, and
      at the same time, the rational use of traditional Chinese medicine, such as
      Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma also should be paid
      attention to. However, due to the GRADE evidence grading of the primary outcome
      measure of 24 h UTP had very low quality, this review can not provide high
      quality evidence to prove the clinical efficacy of this method. More well
      designed and large-scale multi-center randomized controlled trials should be
      conducted in the future for verification.

PMID- 29218951
TI  - [Research on compatibility of prescriptions including Ginseng Radix et Rhizoma
      and Trogopterus Dung based on complex network analysis].
AB  - The applications of prescriptions including Ginseng Radix et Rhizoma and
      Trogopterus Dung in contemporary literatures from 1949 to 2016 are compiled and
      the data mining techniques containing scale-free complex network method are
      utilized to explore its practical characteristics, with comparison between modern
      and ancient ones. The results indicate that malignant neoplasms, coronary heart
      disease which present Qi deficiency and blood stasis type are the main diseases
      treated by prescriptions including Ginseng Radix et Rhizoma and Trogopterus Dung
      according to the reports during 1949 to 2016. The complex network connection
      shows that Glycyrrhizae Radixet Rhizoma, Angelicae Sinensis Radix, Astragali
      Radix, Typhae Pollen, Salviae Miltiorrhizae Radix et Rhizoma are the primary
      drugs related to Ginseng Radix et Rhizoma and Trogopterus Dung. The next are
      Paeoniae Radix Alba, Atractylodis Macrocephalae Rhizoma, Persicae Semen, Foria,
      et al. Carthami Flos, Notoginseng Radix et Rhizoma, Cyperi Rhizoma, Bupleuri
      Radix are the peripheral ones. Also, Ginseng Radix et Rhizoma-Glycyrrhizae
      Radixet Rhizoma, Trogopterus Dung-Glycyrrhizae Radixet Rhizoma, Ginseng Radix et
      Rhizoma-Angelicae Sinensis Radix, Trogopterus Dung-Angelicae Sinensis Radix,
      Ginseng Radix et Rhizoma-Astragali Radix, Trogopterus Dung-Astragali Radix are
      the main paired drugs. The paired drugs including Ginseng Radix et Rhizoma
      Trogopterus Dung-Glycyrrhizae Radixet Rhizoma, Ginseng Radix et Rhizoma
      Trogopterus Dung-Angelicae Sinensis Radix, Ginseng Radix et Rhizoma-Trogopterus
      Dung-Astragali Radix, Ginseng Radix et Rhizoma-Trogopterus Dung-Typhae Pollen
      have a higher support degree. The main compatible drugs are different in ancient
      and modern prescriptions including Ginseng Radix et Rhizoma and Trogopterus Dung.
      Notoginseng Radix et Rhizoma, Typhae Pollen, Salviae Miltiorrhizae Radix et
      Rhizoma, Astragali Radix are utilized frequently in modern prescriptions while
      less used in ancient ones. It is also shown that more attentions are paid to the
      drugs contributing to invigorating Qi and promoting blood circulation in modern
      times with comparative results between modern and ancient prescriptions.

PMID- 29218952
TI  - [Research strategies for feed additives and veterinary medicines from side
      products of Chinese medicine resources industrialization].
AB  - The global antimicrobial resistance has been a big challenge to the human health
      for years. It has to make balance between the safety of animal products and the
      use of antimicrobials in animal husbandry. Any methods that can minimize or even
      phase out the use of antimicrobials in animal husbandry should be encouraged. We
      herein describe the research strategies for feed additives and veterinary
      medicines from the side products of Chinese medicine resources industrialization.
      Killing two birds with one stone-besides the major purposes, the rational
      utilization of non-medicinal parts and wastes of industrialization of Chinese
      herbal medicines is also achieved under the proposed strategies.

PMID- 29218953
TI  - [Exploiture and application of an internet-based Computation Platform for
      Integrative Pharmacology of Traditional Chinese Medicine].
AB  - Recently, integrative pharmacology(IP) has become a pivotal paradigm for the
      modernization of traditional Chinese medicines(TCM) and combinatorial drugs
      discovery, which is an interdisciplinary science for establishing the in vitro
      and in vivo correlation between absorption, distribution, metabolism, and
      excretion/pharmacokinetic(ADME/PK) profiles of TCM and the molecular networks of
      disease by the integration of the knowledge of multi-disciplinary and multi
      stages. In the present study, an internet-based Computation Platform for IP of
      TCM(TCM-IP, www.tcmip.cn) is established to promote the development of the
      emerging discipline. Among them, a big data of TCM is an important resource for
      TCM-IP including Chinese Medicine Formula Database, Chinese Medical Herbs
      Database, Chemical Database of Chinese Medicine, Target Database for Disease and
      Symptoms, et al. Meanwhile, some data mining and bioinformatics approaches are
      critical technology for TCM-IP including the identification of the TCM
      constituents, ADME prediction, target prediction for the TCM constituents,
      network construction and analysis, et al. Furthermore, network beautification and
      individuation design are employed to meet the consumer's requirement. We firmly
      believe that TCM-IP is a very useful tool for the identification of active
      constituents of TCM and their involving potential molecular mechanism for
      therapeutics, which would wildly applied in quality evaluation, clinical
      repositioning, scientific discovery based on original thinking, prescription
      compatibility and new drug of TCM, et al.

PMID- 29218954
TI  - [Study on formation and changes of Dao-di herbs production origin of Gastrodia
      elata].
AB  - Gastrodia elata has been used in China for more than 2 000 years and it is a kind
      of valuable traditional Chinese medicine. The originrecords of G. elata were
      Mount Tai of Shandong and and Mount Song of Henan, which began in Wupu Bencao of
      Wei Jin Dynasties, and Tai'an and its surrounding areas had been the Do-di herbs
      production areas. But from the beginning of the Republic of China, G. elata
      origin has undergone major changes, Do-di herbs production areas moved westward
      to the southwest.In this paper,through literature research and field visits, we
      studied the formation and changes of Do-di herbs production areas of G. elata.
      The cultivation history and current main producing area of G. elata was also
      introduced. On this basis, we profoundly summarized the reasons of Do-di herbs
      production areas formation and changes from the nature, society, transportation,
      humanities and germplasm resources.Combining the ancient herbal medicine and the
      characteristics of modern producing areas, the planting strength of G. elata
      could be strengthened in the hope of providing reference for the quality
      evaluation and cultivation of G. elata.

PMID- 29218955
TI  - Would reframing aged care facilities as a 'hospice' instead of a 'home' enable
      older people to get the care they need?

PMID- 29218956
TI  - Incidence of complications in men undergoing transurethral resection of the
      prostate.
AB  - Objectives: To examine the link between medication use and the risk of bleeding
      complications following transurethral resection of the prostate from the second
      postoperative day until hospital discharge. Method: Using a retrospective
      observational study design, the medical records of all patients who underwent
      transurethral resection of the prostate over a 24-month period were examined.
      Comprehensive data regarding patients' medication history, comorbidities and
      complications that occurred either during or after surgery were collected from
      medical records. Inferential statistical analysis was used to examine
      associations between demographic and medication variables and the risk of
      complications. Results: Complications arising after surgery occurred in 48/135
      (36%) of patients. The most common complications postoperatively were hematuria,
      occurring in 41/48 (85%) and hematuria with clot retention, occurring in 24/48
      (50%) of patients who suffered complications. There was a significant association
      between the number of medications prescribed and postoperative complications; for
      hematuria, chi2 (12) = 21.50, p = 0.04; and for hematuria with clot retention
      chi2 (12) = 24.97, p = 0.015. Conclusions: Demographic data relating to patients'
      age, comorbid state and the number of standard medications prescribed is
      associated with an increase in macroscopic hematuria and macroscopic hematuria
      with clot retention after transurethral resection of the prostate. These findings
      emphasize the importance of nursing practice in both preoperative and
      postoperative care of patients undergoing surgery. Nurses need to be very
      vigilant in assessing patients at risk of increased bleeding from a transurethral
      resection of the prostate by examining their medication regimen.

PMID- 29218957
TI  - Impact of health literacy on medication adherence in older people with chronic
      diseases.
AB  - Medication adherence is a key factor of the therapy of chronic diseases in older
      people with chronic diseases. Inadequate health literacy results in poor health
      outcomes. Therefore, the aim of this study is to investigate the effect of health
      literacy on medication adherence to provide information for improving health
      outcomes in older people with chronic disease. This was a cross-sectional study
      of older people (people aged over 65 years) with chronic diseases in Korea taking
      one or more medications for 6 months and over from an academic referral medical
      center. Each patient completed a structured questionnaire by interview or self
      report. Of the 291 older participants, 30.6% had high medication adherence. In
      hierarchical multiple regression analysis, health literacy was the strongest
      predictor of medication adherence (beta = 0.190, P = 0.001). In addition,
      perceived health status, use of magnifying glass, and assistance with medication
      administration were also significant factors related to medication adherence. In
      conclusion, enhancing health literacy may improve medication adherence of older
      people with chronic disease. The development, implementation and evaluation of
      health literacy interventions for older people with chronic conditions are
      important to increase medication adherence and potentially improve patient
      outcomes. Such programs would also raise awareness of the impact of health
      literacy on patient outcomes. Furthermore, this could contribute to reducing
      health inequalities worldwide.

PMID- 29218958
TI  - Factors contributing to nursing team work in an acute care tertiary hospital.
AB  - Background: Effective nursing teamwork is an essential component of quality
      health care and patient safety. Understanding which factors foster team work
      ensures teamwork qualities are cultivated and sustained. Objective: This study
      aims to investigate which factors are associated with team work in an Australian
      acute care tertiary hospital across all inpatient and outpatient settings.
      Methods: All nurses and midwives rostered to inpatient and outpatient wards in an
      acute care 600 bed hospital in Sydney Australia were invited to participate in a
      cross sectional survey between September to October 2013. Data were collected,
      collated, checked and analysed using Statistical Package for the Social Sciences
      (SPSS) Version 21. Factors reporting a significant correlation with where p <
      0.05 were analysed in a multiple regression model. Results: A total of 501
      surveys were returned. Nursing teamwork scores ranged between 3.32 and 4.08.
      Teamwork subscale Shared Mental Model consistently rated the highest. Mean scores
      for overall communication between nurses and team leadership were 3.6 (S.D. 0.57)
      and 3.8 (SD 0.6) respectively. Leadership and communication between nurses were
      significant predictors of team work p < 0.001. Conclusion: Our findings describe
      factors predictive of teamwork in an acute care tertiary based hospital setting
      across inpatient and outpatient specialty units. Our findings are of particular
      relevance in identifying areas of nurse education and workforce planning to
      improve nursing team work.

PMID- 29218959
TI  - Self-efficacy, depression and self-care activities of people with type 2 diabetes
      in Turkey.
AB  - Background: Self-efficacy related to self-care behaviors in people with type 2
      diabetes has been well reported. However no work has been reported in Turkey that
      uses reliable instruments to examine the relationships among self-care
      activities, depression and self-efficacy. Aim: This study aims to investigate
      self-care activities, depression and self-efficacy among people with type 2
      diabetes in Turkey. Methods: The sample included 200 patients with type 2
      diabetes from an endocrinology outpatient clinic at a university hospital. Self
      care activities, self-efficacy, and symptoms of depression were measured using
      established instruments: The Summary for Diabetes Self-Care Activities, the Self
      Efficacy Scale, and the Beck Depression Inventory. Descriptive and correlational
      statistics were used in data analysis. Findings: One in three (37.5%) of
      participants had depression symptoms. Beck Depression Inventory scores were
      higher in women and in those with a lower education level, had diabetic
      complications and difficulty in meeting health care costs. The mean self-efficacy
      score was 66.5 +/- 14.0; those who lived alone, were unemployed and knew their
      HbA1c level had significantly higher scores (p < .05). Demographic and diabetes
      characteristics including age, education, social support, diabetes complications,
      HbA1c level, and having diabetes education were found to be significantly
      associated with all self-care activities except smoking. Conclusion: The
      association between self-efficacy and self-care activities was positive.
      Interventions to improve patients' self-efficacy and self-care are needed in
      order to maximize diabetes self-management.

PMID- 29218960
TI  - Shifting the load: Improving bioscience performance in undergraduate nurses
      through student focused learning.
AB  - Background: Bioscience has a long history of being challenging to teach and learn
      within nursing courses and little has been published on new ways to assist
      students in their learning. The aim of this study was to determine which of three
      different interventions would assist student performance in a nursing bioscience
      unit. Method: To begin, the contribution of recent prior learning in science was
      investigated by comparing the final exam marks of 182 students in the bioscience
      unit with the science marks they achieved at high (secondary) school. The effect
      of recent prior learning was then tested by investigating whether the first
      intervention, a pre-nursing bioscience workshop of 63 students, would substitute
      for recent high school science. Two further interventions were tested that used a
      stronger student-focused contribution to the teaching and learning within the
      bioscience unit. These were the Human Body Club which was composed of 44 under
      performing students and an online learning platform known as LearnSmart that was
      used by a cohort of 263 students. Results and discussion: Good and recent high
      school attainment in the sciences did improve student performance, whilst recent
      prior learning in the form of a bioscience workshop did not. Both student-focused
      interventions improved student performance. The longer a student spent using
      LearnSmart the more their mark increased. However, the Human Body Club which
      provided additional support and shifted the bulk of the teaching and learning to
      the students was the most effective of the three interventions in assisting
      students to pass the bioscience unit.

PMID- 29218961
TI  - The black and white and shades of grey of boundary violations.
AB  - Using a Constructivist Grounded Theory approach (Charmaz, 2006), this research
      examined the social construct of the "professional boundary" necessary in mental
      health therapeutic work and the problem of professional boundary violations in
      the therapeutic relationship. Thirteen mental health clinicians from various
      professional disciplines commonly found in mental health clinical practice
      responded to three specific questions designed to gain an understanding about how
      clinicians gauge the differences between minor and serious boundary violations.
      The three questions facilitated further exploration of boundary violations
      specifically to explore the difficulties of determining what is and what is not
      considered a boundary violation often resulting in polarised views or "black and
      white" descriptions and opinions. However many shades of grey were also revealed
      during the interviews.Almost all participants rated intimacy or sexual contact
      with a client or an ex-client as being a serious boundary violation, on the other
      hand there was a great deal of variety in the examples offered as minor boundary
      violations. Whilst the "Black" is clearly defined by clinicians in this research,
      the "White" only seemed to create more "Grey" areas, with descriptions of
      behaviours that fell into the Grey area being more difficult to define.

PMID- 29218962
TI  - Schistosomiasis and soil-transmitted helminthiases: number of people treated in
      2016.

PMID- 29218963
TI  - Mental health recovery: A review of the peer-reviewed published literature.
AB  - The concept of mental health recovery promotes collaborative partnership among
      consumers, carers and service providers. However views on mental health recovery
      are less explored among carers and service providers. The aim of this review was
      to analyse contemporary literature exploring views of mental health consumers,
      carers and service providers in relation to their understanding of the meaning of
      mental health recovery and factors influencing mental health recovery. The
      literature review questions were: How is mental health recovery and factors
      influencing mental health recovery viewed by consumers, carers and service
      providers? What are the differences and similarities in those perceptions? How
      can the outcomes and recommendations inform the Australian mental health
      practices? A review of the literature used selected electronic databases and
      specific search terms and supplemented with manual searching. Twenty-six studies
      were selected for review which included qualitative, mixed method, and
      quantitative approaches and a Delphi study. The findings indicated that the
      concept of mental health recovery is more explored among consumers and is seldom
      explored among carers and service providers. The studies suggested that recovery
      from mental illness is a multidimensional process and the concept cannot be
      defined in rigid terms. In order to achieve the best possible care, the
      stakeholders require flexible attitudes and openness to embrace the philosophy.

PMID- 29218964
TI  - New perspectives on understanding cultural diversity in nurse-patient
      communication.
AB  - Effective communication is essential in developing rapport with patients, and
      many nursing roles such as patient assessment, education, and counselling consist
      only of dialogue. With increasing cultural diversity among nurses and patients in
      Australia, there are growing concerns relating to the potential for
      miscommunication, as differences in language and culture can cause
      misunderstandings which can have serious impacts on health outcomes and patient
      safety (Hamilton & Woodward-Kron, 2010). According to Grant and Luxford (2011))
      there is little research into the way health professionals approach working with
      cultural difference or how this impacts on their everyday practice. Furthermore,
      there has been minimal examination of intercultural nurse-patient communication
      from a linguistic perspective. Applying linguistic frameworks to nursing practice
      can help nurses understand what is happening in their communication with
      patients, particularly where people from different cultures are interacting. This
      paper discusses intercultural nurse-patient communication and refers to
      theoretical frameworks from applied linguistics to explain how miscommunication
      may occur. It illustrates how such approaches will help to raise awareness of
      underlying causes and potentially lead to more effective communication skills,
      therapeutic relationships and therefore patient satisfaction and safety.

PMID- 29218965
TI  - Moral courage in undergraduate nursing students: A literature review.
AB  - Aim: The aim of this review was to explore factors which facilitate or inhibit
      undergraduate nursing students' willingness to demonstrate moral courage when
      confronted by poor patient care. Methods: Included papers were those that met the
      criteria of being qualitative research that explored undergraduate nursing
      students' depictions of situations where moral courage was or was not
      demonstrated during clinical placements, with a particular focus on situations
      that impacted or had the potential to impact the quality of patient care.Papers
      were reviewed using the Critical Appraisal Skills Programme Qualitative Research
      Checklist. The 15 papers included in the review were then thematically analysed.
      Findings: The literature reports, despite feeling a moral obligation to act, most
      nursing students lack the moral courage to intervene or speak up when faced with
      poor practice. While students may subsequently report the behaviour, at the time
      of the event, they often remain passive spectators and sometimes even active
      participants. The major themes identified in the literature were: just a student,
      don't rock the boat, fear of consequences, mentor-student relationship, and
      patient advocate identity. The literature also identified that nursing students
      suffer ongoing moral distress when they do not have the courage to confront poor
      practice. Conclusion: There is a need for further research to explore positive
      examples of how nursing students demonstrate moral courage when undertaking
      clinical placements. These narratives have the potential to influence future
      students' attitudes, values and behaviours by providing stimulus materials for
      teaching.

PMID- 29218966
TI  - Building compassion literacy: Enabling care in primary health care nursing.
AB  - This paper introduces the concept of compassion literacy and discusses its place
      in nursing within the general practice setting. Compassion literacy is a valuable
      competency for sustaining the delivery of high quality care. Being compassion
      literate enables practice nurses to provide compassionate care to their patients
      and to recognise factors that may constrain this. A compassion literate practice
      nurse may be more protected from compassion fatigue and its negative
      consequences. Understanding how to enable self-compassion and how to support the
      delivery of compassionate care within the primary care team can enhance the care
      experienced by the patient while improving the positive engagement and
      satisfaction of the health professionals. The capacity to deliver compassionate
      care can be depleted by the day-to-day demands of the clinical setting.
      Compassion literacy enables the replenishing of compassion, but the development
      of compassion literacy can be curtailed by personal and workplace barriers. This
      paper articulates why compassion literacy should be an integral aspect of
      practice nursing and considers strategies for enabling compassion literacy to
      develop and thrive within the workplace environment. Compassion literacy is also
      a valuable opportunity for practice nurses to demonstrate their key role within
      the multidisciplinary team of general practice, directly enhancing the quality of
      the care delivered.

PMID- 29218967
TI  - Call for national dialogue: Adapting standards of care in extreme events. We are
      not ready.
AB  - Clinical practices are based on a common understanding of nursing's professional
      standards in all aspects of patient care, no matter what the circumstances are.
      Circumstances can however, change dramatically due to emergencies, disasters, or
      pandemics and may make it difficult to meet the standard of care in the way
      nurses are accustomed. The Australian nursing profession has not yet facilitated
      a broad discussion and debate at the professional and institutional level about
      adapting standards of care under extreme conditions, a dialogue which goes beyond
      the content of basic emergency and disaster preparedness. The purpose of this
      paper is to encourage discussion within the nursing profession on this important
      ethical and legal issue. A comprehensive review of the literature was undertaken
      to determine the state of the evidence in relation to adapting standards of care
      under extreme conditions. Content analysis of the literature identified
      categories related to adapting standards of care that have been considered by
      individuals or groups that should be considered in Australia, should a dialogue
      be undertaken.The categories include ethical expectations of professional
      practice; legal interpretation of care requirements, resource priority between
      hospital and public health and informing communities.Literature reviews and
      commentary may provide the background for a national dialogue on the nursing
      response in an extreme event. However, it is only with the engagement of a
      broadly representative segment of the professional nursing community that
      appropriate guidance on adapting standards of care under extreme conditions can
      be developed and then integrated into the professional worldview of nursing in
      Australia.

PMID- 29218968
TI  - The psychiatry-integrated nurse practitioner role in hemodialysis: An opportunity
      to provide nurse practitioner care between the interface of psychiatry and
      hemodialysis.
AB  - The mental health of patients living with end-stage kidney disease (ESKD) is an
      important aspect of their care. According to national survey data, depressive
      disorders affect about 9% of the North American population (Kessler, Chiu,
      Demler, Merikangas, & Walters, 2005). A review of psychological distress and
      depression across the spectrum of chronic kidney disease indicates that the
      prevalence of depression in ESKD is reported to be about four times that of the
      general population and it is associated with adverse outcomes including low
      quality-of-life ratings, graft failure, and death after renal transplantation
      (Zalai, Szeifert, & Novak, 2012). At St. Michael's Hospital (SMH), patients on
      hemodialysis (HD) requiring psychiatry consultation had traditionally been
      referred to a dedicated outpatient psychiatrist. This presented challenges around
      access to psychiatry assessment and follow-up, as patients were reluctant to
      attend appointments outside of HD visits. The team recognized these challenges
      and addressed them through the introduction of the Medical Psychiatry NP (MP NP)
      role, as the point-of-care consultant in HD.

PMID- 29218969
TI  - Acute kidney injury secondary to lymphoma.

PMID- 29218970
TI  - Are you SURE about your vascular access? Exploring factors influencing vascular
      access decisions with chronic hemodialysis patients and their nurses.
AB  - A major decision for patients with stage 5 chronic kidney disease (CKD) relates
      to vascular access (VA) for treatment. Patients who receive pre-dialysis care
      often defer making a decision, which results in initiation of hemodialysis (HD)
      with a central venous catheter (CVC) in an urgent or emergent situation. Little
      is known about how individuals make decisions around VA. In this context, a mixed
      methods study was undertaken to explore uncertainty related to changing their VA
      from an existing CVC to a graft or fistula. Quantitative assessment was measured
      using the SURE tool and interviews with patients and nurses were conducted.
      Results revealed that none of the 16 patient participants reported uncertainty.
      Qualitative findings revealed that patient decisions about access were impacted
      by observations, experiences, and dialogue in the hemodialysis unit. Study
      findings have important implications including the challenge of reconciling
      epidemiologic population-based risk measurement to the individual patient's
      situation. Moreover, the SURE tool was viewed as a mechanism to open a dialogue
      to confirm patients' decisions and provide further education and/or support
      following HD initiation.

PMID- 29218971
TI  - An Evaluation of Medication Reconciliation in an Outpatient Nephrology Clinic.
AB  - Background: Accreditation Canada recognizes medication reconciliation as a key
      required organizational practice (ROP) to enhance patient safety. Patients with
      chronic kidney disease (CKD) carry a high risk for adverse drug events due to
      multiple co-morbidities, using many medications, and being cared for by many
      practitioners. Data evaluating the benefits of ambulatory medication
      reconciliation (AmbMR) in patients with advanced CKD is limited. Methods: We
      retrospectively evaluated types and rates of medication discrepancies and their
      potential index for patient harm using the Cornish classification system in a
      cohort of consecutive non-dialysis-dependent CKD stage 5 patients who received
      AmbMR. Results: AmbMR was conducted 225 times on 115 patients during the study
      period. One hundred eighty medication discrepancies were identified. The most
      common discrepancy identified was incorrect drug followed by discrepant dose,
      discrepant frequency, and drug omission. Sixty-three percent of discrepancies
      were classified as unlikely to cause patient discomfort or clinical
      deterioration, 36% were classified as likely to cause moderate harm, and one
      percent was classified as potential to cause serious harm. Conclusion: Medication
      discrepancies are common in patients with advanced CKD. Nearly a quarter of
      patients may experience moderate discomfort or clinical deterioration from
      discrepancies. Our study showed that in patients with non-dialysis-dependent CKD
      stage 5, the risk of patient harm associated with medication discrepancies can be
      reduced by conducting AmbMR.

PMID- 29218972
TI  - The Canadian Organ Replacement Register: From data submission to final reports.

PMID- 29218973
TI  - Recent Changes in Anemia Management: The Kidney Disease Improving Global Outcomes
      (KDIGO) Anemia Guideline versus the Canadian Society of Nephrology (CSN).
AB  - The management of anemia is important for health outcomes for people with chronic
      kidney disease (CKD). Global evidenced-based guidelines must be placed in the
      Canadian context to be relevant to guide practice. This paper summarizes the
      response of the Canadian Society of Nephrology to global anemia management
      guidelines in CKD and the implications for practice.

PMID- 29218974
TI  - Blood pressure management in patients on hemodialysis.

PMID- 29218975
TI  - Opportunities and challenges caring for young adults on hemodialysis awaiting
      transplant.

PMID- 29218976
TI  - An interprofessional team that includes a nurse practitioner and patients with
      diabetes and chronic kidney disease.
AB  - Diabetes is the leading cause of chronic kidney disease (CKD). The clinical
      practice guidelines of the Canadian Diabetes Association were updated in 2013. We
      sought to identify the level of adherence to the CDA guidelines of an
      interprofessional team in a pre-dialysis clinic that includes a nurse
      practitioner, and examine how team members integrated the guidelines and
      optimized each provider's role. A mixed methods study was undertaken. Chart
      audits (n= 146) identified 10 patients who met the inclusion criteria. The level
      of adherence to the CDA guidelines was high for several indicators; yet a number
      of care activities were not well documented in the health record. Interviews (n=
      7) with interprofessional team members identified specific strategies used by
      providers to incorporate the guidelines and optimize each team members's role.
      Accurate documentation of care activities is essential to assessing adherence to
      guidelines and informing decisions about care.

PMID- 29218977
TI  - Motivational interviewing: Application to end stage renal disease patients.

PMID- 29218978
TI  - Blood specimen labelling errors: Implications for nephrology nursing practice.
AB  - Patient safety is the foundation of high-quality health care, as recognized both
      nationally and worldwide. Patient blood specimen identification is critical in
      ensuring the delivery of safe and appropriate care. The practice of nephrology
      nursing involves frequent patient blood specimen withdrawals to treat and monitor
      kidney disease. A critical review of the literature reveals that incorrect
      patient identification is one of the major causes of blood specimen labelling
      errors. Misidentified samples create a serious risk to patient safety leading to
      multiple specimen withdrawals, delay in diagnosis, misdiagnosis, incorrect
      treatment, transfusion reactions, increased length of stay and other negative
      patient outcomes. Barcode technology has been identified as a preferred method
      for positive patient identification leading to a definitive decrease in blood
      specimen labelling errors by as much as 83% (Askeland, et al., 2008). The use of
      a root cause analysis followed by an action plan is one approach to decreasing
      the occurrence of blood specimen labelling errors. This article will present a
      review of the evidence-based literature surrounding blood specimen labelling
      errors, followed by author recommendations for completing a root cause analysis
      and action plan. A failure modes and effects analysis (FMEA) will be presented as
      one method to determine root cause, followed by the Ottawa Model of Research Use
      (OMRU) as a framework for implementation of strategies to reduce blood specimen
      labelling errors.

PMID- 29218979
TI  - Facilitating communication with the patient with a language barrier.

PMID- 29218980
TI  - Safety of Radiographic Imaging in Pregnancy
AB  - There are many false assumptions, both in the general population and among
      physicians, regarding the influence of radiation on pregnant patients and the
      fetus during diagnostic procedures, in spite of scientific facts based on
      studies. These false assumptions are mostly based on the idea that every
      diagnostic procedure using ionizing radiation is a cause for serious concern and
      that artificial abortion as a possible solution might be considered. We analyzed
      data from counseling of pregnant patients exposed to ionizing radiation during
      diagnostic procedures in the Merkur University Hospital during a 4-year period.
      In this period, 26 patients presented for counseling after exposure to diagnostic
      ionizing radiation during pregnancy. Results showed most of these patients to
      have been exposed to radiation between the 2nd and 3rd week of gestation (36%),
      between the 4th and 5th week 32%, before the 2nd week 24%, and after the 6th week
      of gestation less than 8%. To provide reasonable estimate of fetal doses, Report
      No. 174 from the National Council on Radiation Protection and Measurements (NCRP)
      was used. Data from the Report include estimate of the fetal dose from direct and
      indirect exposures. Th e mean doses were up to 0.01 cGy in 46.2%, 0.01-0.15 cGy
      in 19.2%, 0.2-1 cGy in 26.9% and 1 cGy or more in 7.7% of patients. None of the
      counseled patients had medical indication for abortion, even though in a small
      percentage of patients abortion was a personal subjective decision. Considering
      that there are no Croatian guidelines for counseling patients exposed to ionizing
      radiation during pregnancy, it is recommended to use the International Commission
      on Radiological Protection guidelines in the management of pregnant patients
      exposed to ionizing radiation.

PMID- 29218981
TI  - Extraordinary Porous Few-Layer Carbons of High Capacitance from Pechini
      Combustion of Magnesium Nitrate Gel.
AB  - Highly capacitive carbons are viewed as promising commercial materials for
      supercapacitors, but few species satisfy the requirements of high capacitance and
      low cost. Here, we demonstrate an extraordinary porous few-layer carbon by facile
      Pechini combustion of magnesium nitrate gel, which combined salicylic acid as a
      complexing agent with magnesium nitrate as an inorganic metal salt. The as
      synthesized carbon material delivers a capacitance of 415 F g-1, mostly stemming
      from a large specific surface area (~1312 m2 g-1), a fluent channel for transport
      of the electrolyte, as well as electrochemical redox reactions at O,N-associated
      active sites. Such porous few-layer carbons may accelerate the adoption of carbon
      based supercapacitors for commercial high-power energy storage applications.

PMID- 29218982
TI  - Discovery of a Novel Polyfluoroalkyl Benzenesulfonic Acid around Oilfields in
      Northern China.
AB  - The existence of more than 3000 per- and polyfluoroalkyl substances (PFASs) on
      the global market has prompted the identification and hazard characterization of
      hitherto unknown PFASs. In the present study, a novel PFAS, sodium p-perfluorous
      nonenoxybenzenesulfonate (OBS), was identified using Orbitrap MS/MS in water
      samples around a suspected application area, Daqing Oilfield, China. The peak OBS
      concentration was 3.2 * 103 ng/L in a sample taken near the oil well with the
      longest production history in Daqing. The concentrations of OBS and contribution
      to the sum of PFASs in surface waters displayed considerable variation among the
      three sampling areas (mean levels at 6.9, 50, and 5.6 * 102 ng/L with mean
      percentages at 9.8%, 45%, and 69% in the background, new and old oilfield areas
      respectively) confirming that the density of oil wells and the oil production
      history are important factors influencing OBS contamination in the studied areas.
      A preliminary assessment of acute toxicity and environmental fate indicates that
      OBS exhibits similar toxicity and environmental persistence to
      perfluorooctanesulfonic acid (PFOS). The widespread occurrence of OBS, in
      conjunction with its potential hazard properties, underscores the need to further
      study on the bioaccumulation and potential for human exposure.

PMID- 29218983
TI  - Electrochemical Fouling of Dopamine and Recovery of Carbon Electrodes.
AB  - A significant problem with implantable sensors is electrode fouling, which has
      been proposed as the main reason for biosensor failures in vivo. Electrochemical
      fouling is typical for dopamine (DA) as its oxidation products are very reactive
      and the resulting polydopamine has a robust adhesion capability to virtually all
      types of surfaces. The degree of DA fouling of different carbon electrodes with
      different terminations was determined using cyclic voltammetry (CV) and scanning
      electrochemical microscopy (SECM) approach curves and imaging. The rate of
      electron transfer kinetics at the fouled electrode surface was determined from
      SECM approach curves, allowing a comparison of insulating film thickness for the
      different terminations. SECM imaging allowed the determination of different
      morphologies, such as continuous layers or islands, of insulating material. We
      show that heterogeneous modification of carbon electrodes with carboxyl-amine
      functionalities offers protection against formation of an insulating polydopamine
      layer, while retaining the ability to detect DA. The benefits of the
      heterogeneous termination are proposed to be due to the electrostatic repulsion
      between amino-functionalities and DA. Furthermore, we show that the conductivity
      of the surfaces as well as the response toward DA was recovered close to the
      original performance level after cleaning the surfaces for 10-20 cycles in H2SO4
      on all materials but pyrolytic carbon (PyC). The recovery capacity of the PyC
      electrode was lower, possibly due to stronger adsorption of DA on the surface.

PMID- 29218984
TI  - Catalytic Organic Reactions in Water toward Sustainable Society.
AB  - Traditional organic synthesis relies heavily on organic solvents for a multitude
      of tasks, including dissolving the components and facilitating chemical
      reactions, because many reagents and reactive species are incompatible or
      immiscible with water. Given that they are used in vast quantities as compared to
      reactants, solvents have been the focus of environmental concerns. Along with
      reducing the environmental impact of organic synthesis, the use of water as a
      reaction medium also benefits chemical processes by simplifying operations,
      allowing mild reaction conditions, and sometimes delivering unforeseen
      reactivities and selectivities. After the "watershed" in organic synthesis
      revealed the importance of water, the development of water-compatible catalysts
      has flourished, triggering a quantum leap in water-centered organic synthesis.
      Given that organic compounds are typically practically insoluble in water, simple
      extractive workup can readily separate a water-soluble homogeneous catalyst as an
      aqueous solution from a product that is soluble in organic solvents. In contrast,
      the use of heterogeneous catalysts facilitates catalyst recycling by allowing
      simple centrifugation and filtration methods to be used. This Review addresses
      advances over the past decade in catalytic reactions using water as a reaction
      medium.

PMID- 29218985
TI  - Stable and Photoswitchable Carbon-Dot Liposome.
AB  - Carbon-dot (C-dot) liposome consisting of several thousands of C-dots shows
      interesting photoswitching properties. The water-dispersible C-dot liposome
      possesses intrinsic photoluminescence (PL) and is stable against salt and
      photoirradiation. The PL of C-dot liposome can be turned off and then on under
      photoirradiation over the wavelength regions of 510-540 nm and 365-420 nm,
      respectively. Like reported C-dots, the C-dot liposome emits various colors when
      excited at different wavelengths. Having great stability and high contrast,
      images of individual C-dot liposome have been recorded, showing negligible
      photoblinking. Through a simple photolithographic approach, micropatterns of C
      dot liposomes emitting different colors have been fabricated.

PMID- 29218986
TI  - Collection Method of SERS Active Nanoparticles for Sensitive and Precise
      Measurements.
AB  - Developing surface-enhanced Raman spectroscopy (SERS) based biosensors requires
      not only synthesizing SERS active nanoparticles or nanoprobes that produce
      intense signal but also collecting them in a consistent manner to obtain
      sensitive and precise measurements. Nanoprobes are commonly measured in solution;
      however, this approach has several disadvantages that can reduce sensitivity,
      such as probing only a small percentage of the nanoprobes present in the sample.
      In this work, a novel collection device was designed, built, and tested which
      consistently concentrates nanoprobes in a specific area to yield highly sensitive
      (femtomolar) and repeatable measurements. A particular silica nanoprobe composed
      of aggregated silver nanoparticles with Raman reporters on them was synthesized
      and functionalized to measure it on the collection device. The collection device
      was assessed by collecting several concentrations of nanoprobes and comparing
      their SERS intensities to determine their limit of detection and the precision on
      the device. In addition, a competitive binding assay to detect cardiac Troponin I
      (cTnI) was used as an example to demonstrate the functionality of the nanoprobe
      and collection device. Nanoprobe samples (10 MUL) were detected with less than
      10% coefficient of variation (CV) across a range from nearly 27.4 fM to 1.7 pM
      using the described collection method. In the example assay, several cTnI
      concentrations ranging from 0 to 250 ng/mL were detected.

PMID- 29218987
TI  - Simple Synthesis of Au-Pd Alloy Nanowire Networks as Macroscopic, Flexible
      Electrocatalysts with Excellent Performance.
AB  - The present work introduces a new way to prepare Au-Pd alloy nanowire networks
      (NWNs) via deposition of Pd atoms onto Au nanowires in reaction media at room
      temperature without the aid of additional reducing agents. Thanks to their
      excellent colloidal stability in water as well as in ethanol, the resulting NWNs
      can be utilized to produce composite thin films with Nafion (perfluorinated
      sulfonic acid) with dimensions above dozens of square centimeters by means of
      solution casting on the glass substrate. Most importantly, these films can be
      easily transferred onto different solid substrates by lift-off technology.
      Moreover, the resulting Au-Pd alloy NWNs can also be easily and thoroughly loaded
      into macroscopic carbon fiber cloth (CFC). Both the Au-Pd alloy NWN/Nafion
      composite film and the Au-Pd alloy NWN-loaded CFC can be used as flexible
      electrodes for electrocatalysis of ethanol oxidation, with electrocatalytic
      performance at different distorted states superior by 2 orders of magnitude to
      those reported in the literature (e.g., commercial Pd/C catalysts and Pd-based
      nanostructured catalysts). This work opens new possibilities for the large-scale
      manufacturing of electrodes for fuel cells.

PMID- 29218988
TI  - Access to 2,6-Disubstituted 4-Oxopiperidines Using a 6-Endo-trig Cyclization:
      Stereoselective Synthesis of Spruce Alkaloid and (+)-241D.
AB  - A synthetic route to cis-2-methyl-4-oxo-6-alkylpiperidines has been developed
      using a 6-endo-trig cyclization of (E)-enones. The base-mediated intramolecular
      cyclization was found to be general for both alkyl- and aryl-substituted enones,
      providing the corresponding 4-oxopiperidines in high yields (80-89%).
      Stereoselective reduction of the 2,6-cis-disubstituted 4-oxopiperidines then gave
      the 2,4,6-cis,cis-trisubstituted 4-hydroxypiperidines in high
      diastereoselectivity. The general nature of this approach was demonstrated with
      the synthesis of the natural products, spruce alkaloid and (+)-241D.

PMID- 29218989
TI  - Redox-Tag Processes: Intramolecular Electron Transfer and Its Broad Relationship
      to Redox Reactions in General.
AB  - Explosive growth in the use of open shell reactivity, including neutral radicals
      and radical ions, in the field of synthetic organic chemistry has been observed
      in the past decade, particularly since the advent of ruthenium complexes in 2008.
      These complexes generally induce single-electron transfer (SET) processes via
      visible-light absorption. Additionally, recent significant advancements in
      organic electrochemistry involving SET processes to provide open shell reactivity
      offer a complementary method to traditional polarity-driven reactions described
      by two-electron transfer processes. In this Review, we highlight the importance
      of intramolecular SET processes in the field of synthetic organic chemistry,
      which seem to be more elusive than the intermolecular versions, since they are
      net redox-neutral and thus cannot simply be regarded as oxidations or reductions.
      Such intramolecular SET processes can rationally be understood in combination
      with concomitant bond formations and/or cleavages, and are regulated by a
      structural motif that we call a "redox tag." In order to describe modern radical
      driven reactions involving SET processes, we focus on a classical formalism in
      which electrons are treated as particles rather than waves, which offers a
      practical yet powerful approach to explain and/or predict synthetic outcomes.

PMID- 29218990
TI  - Heat-Assisted Inkjet Printing of Tungsten Oxide for High-Performance Ultraviolet
      Photodetectors.
AB  - An ammonium metatungstate precursor (WO3Pr) ink was printed for tungsten oxide
      (WO3) UV detectors on SiO2/Si wafers with prefabricated Au electrodes. A
      systematic study was carried out on the printing parameters including substrate
      temperatures in the range of 22-80  degrees C, WO3Pr molar concentrations of
      0.01, 0.02, and 0.03 M, and printing scan numbers up to 7 to understand their
      effects on the resulted WO3 film morphology and optoelectronic properties. It has
      been found that the printing parameters can sensitively affect the WO3 film
      morphology, which in turn impacts the WO3 photodetector performance. In
      particular, the printed films experienced a systematic change from discontinuous
      droplets at below 40  degrees C to continuous films at 40-60  degrees C of the
      substrate temperature. At higher temperatures, the excessive heat from the
      substrate not only caused drastic evaporation of the printed ink, resulting in
      highly nonuniform films, but also detrimental heating of the ink in the printer
      nozzle in proximity of the substrate, preventing continuous printing operation.
      An optimal printing window of the substrate temperature of 45-55  degrees C at a
      molar concentration of 0.02 M of ammonium metatungstate and three printing scans
      was obtained for the best UV detector performance. A large on/off ratio of 3538
      and a high responsivity up to 2.70 A/W at 5 V bias (0.54 A/W.V) represent a
      significant improvement over the best report of ~0.28 MUA/W.V on WOX
      photodetectors, which indicates that the printed WO3 films are promising for
      various applications of optoelectronics and sensors.

PMID- 29218991
TI  - Multimodal Kelvin Probe Force Microscopy Investigations of a Photovoltaic
      WSe2/MoS2 Type-II Interface.
AB  - Atomically thin transition-metal dichalcogenides (TMDC) have become a new
      platform for the development of next-generation optoelectronic and light
      harvesting devices. Here, we report a Kelvin probe force microscopy (KPFM)
      investigation carried out on a type-II photovoltaic heterojunction based on WSe2
      monolayer flakes and a bilayer MoS2 film stacked in vertical configuration on a
      Si/SiO2 substrate. Band offset characterized by a significant interfacial dipole
      is pointed out at the WSe2/MoS2 vertical junction. The photocarrier generation
      process and phototransport are studied by applying a differential technique
      allowing to map directly two-dimensional images of the surface photovoltage (SPV)
      over the vertical heterojunctions (vHJ) and in its immediate vicinity.
      Differential SPV reveals the impact of chemical defects on the photocarrier
      generation and that negative charges diffuse in the MoS2 a few hundreds of
      nanometers away from the vHJ. The analysis of the SPV data confirms unambiguously
      that light absorption results in the generation of free charge carriers that do
      not remain coulomb-bound at the type-II interface. A truly quantitative
      determination of the electron-hole (e-h) quasi-Fermi levels splitting (i.e., the
      open-circuit voltage) is achieved by measuring the differential vacuum-level
      shift over the WSe2 flakes and the MoS2 layer. The dependence of the energy-level
      splitting as a function of the optical power reveals that Shockley-Read-Hall
      processes significantly contribute to the interlayer recombination dynamics.
      Finally, a newly developed time-resolved mode of the KPFM is applied to map the
      SPV decay time constants. The time-resolved SPV images reveal the dynamics of
      delayed recombination processes originating from photocarriers trapping at the
      SiO2/TMDC interfaces.

PMID- 29218992
TI  - Computational Insight Into the Hydroamination of an Activated Olefin, As
      Catalyzed by a 1,2,4-Triazole-Derived Nickel(II) N-Heterocyclic Carbene Complex.
AB  - A density functional theory (DFT) investigation performed at the
      B3LYP/TZVP//B3LYP/6-31G(d)-LANL2DZ level of theory on the hydroamination of
      dimethylamine (Me2NH) on an activated olefin (namely, acrylonitrile (CH2?CHCN)),
      as catalyzed by a 1,2,4-triazol based nickel(II) N-heterocyclic carbene complex
      (namely, [1,4-dimethyl-1,2,4-triazole-5-ylidene]2 nickel dichloride) revealed
      that the olefin coordination pathway is favorable over the amine coordination
      pathway, although the initial olefin coordination step is higher in energy than
      the initial amine coordination step. Significantly enough, the reaction involved
      a crucial 1,3-proton transfer step between the resonance intermediates, i.e., the
      C-bound [(NHC)2Ni(CH(CN)CH2NHMe2)]+ (D) species or N-bound
      [(NHC)2Ni(NCCHCH2NHMe2)]+ (E) species and the intermediate
      [(NHC)2Ni(NCCH2CH2NMe2)]+ (F), depicting the cleavage of a N-H bond and the
      formation of a C-H bond facilitated by a water-assisted/amine-assisted proton
      shuttle. Overall, among the various pathways explored, the lowest energy pathway
      involved alkene coordination, followed by an amine-assisted 1,3-proton transfer
      step.

PMID- 29218993
TI  - Energy Landscape of the Substrate Translocation Equilibrium of Plasma-Membrane
      Glutamate Transporters.
AB  - Glutamate transporters maintain a large glutamate concentration gradient across
      synaptic membranes and are, thus, critical for functioning of the excitatory
      synapse. Mammalian glutamate transporters concentrate glutamate inside cells
      through energetic coupling of glutamate flux to the transmembrane concentration
      gradient of Na+. Structural models based on an archeal homologue, GltPh, suggest
      an elevator-like carrier mechanism. However, the energetic determinants of this
      carrier-based movement are not well understood. Although electrostatics play an
      important role in governing these energetics, their implication on transport
      dynamics has not been studied. Here, we combine a pre-steady-state kinetic
      analysis of the translocation equilibrium with electrostatic computations to gain
      insight into the energetics of the translocation process. Our results show the
      biphasic nature of translocation, consistent with the existence of an
      intermediate on the translocation pathway. In the absence of voltage, the
      equilibrium is shifted to the outward-facing configuration. Electrostatic
      computations confirm the intermediate state and show that the elevator-like
      movement is energetically feasible in the presence of bound Na+ ions, whereas a
      substrate-hopping model is energetically prohibitive. Our results highlight the
      critical contribution of charge compensation to transport and add to results from
      previous molecular dynamics simulations for improved understanding of the
      glutamate translocation process.

PMID- 29218994
TI  - Rh-Catalyzed Asymmetric Hydrogenation of beta-Branched Enol Esters for the
      Synthesis of beta-Chiral Primary Alcohols.
AB  - An asymmetric hydrogenation of beta-branched enol esters has been developed for
      the first time, providing a new route for the synthesis of beta-chiral primary
      alcohols. Using a (S)-SKP-Rh complex bearing a large bite angle and enol ester
      substrates possessing an O-fomyl directing group, the desired products were
      obtained in quantitative yields and with excellent enantioselectivities.

PMID- 29218995
TI  - Enantioselective Synthesis of Spliceostatin G and Evaluation of Bioactivity of
      Spliceostatin G and Its Methyl Ester.
AB  - An enantioselective total synthesis of spliceostatin G has been accomplished. The
      synthesis involved a Suzuki cross-coupling reaction as a key step. The
      functionalized tetrahydropyran ring was constructed from commercially available
      optically active tri-O-acetyl-d-glucal. Other key reactions include a highly
      stereoselective Claisen rearrangement, a Cu(I)-mediated 1,4 addition of MeLi to
      install the C8 methyl group, and a reductive amination to incorporate the C10
      amine functionality of spliceostatin G. Biological evaluation of synthetic
      spliceostatin G and its methyl ester revealed that it does not inhibit splicing
      in vitro.

PMID- 29218996
TI  - Use of Complementary and Alternative Medicine Among Newly Diagnosed Breast Cancer
      Patients in Malaysia: An Early Report From the MyBCC Study.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) has increased
      and little is known on CAM use during the initial period. Therefore, the aim was
      to determine prevalence of CAM use among newly diagnosed breast cancer patients
      prior to seeking conventional treatment. METHODS: This is a cross-sectional study
      involved interviewing newly diagnosed breast cancer patients in the University
      Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible
      respondents were interviewedduring a routine clinical visit. RESULTS: A total of
      400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary
      supplementation (n = 107, 77.0%) was the most frequently used type of CAM,
      followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n
      = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM
      users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority
      of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their
      doctors. Most of them used remedies based on the recommendation of family and
      friends. Malay ethnicity and patients with 3 or more comorbidities were more
      likely to use CAM. CONCLUSION: There is substantial use of CAM among breast
      cancer patients in UMMC prior to seeking hospital treatment, and the most popular
      CAM modality is dietary supplements. Since, the majority of CAM users do not
      disclose the use of CAM to their physicians, therefore health care providers
      should ensure that those patients who are likely to use CAM are appropriately
      counseled and advised.

PMID- 29218997
TI  - Causes of impaired oral vaccine efficacy in developing countries.
AB  - Oral vaccines are less immunogenic when given to infants in low-income compared
      with high-income countries, limiting their potential public health impact. Here,
      we review factors that might contribute to this phenomenon, including
      transplacental antibodies, breastfeeding, histo blood group antigens, enteric
      pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We
      highlight several clear risk factors for vaccine failure, such as the inhibitory
      effect of enteroviruses on oral poliovirus vaccine. We also highlight the
      ambiguous and at times contradictory nature of the available evidence, which
      undoubtedly reflects the complex and interconnected nature of the factors
      involved. Mechanisms responsible for diminished immunogenicity may be specific to
      each oral vaccine. Interventions aiming to improve vaccine performance may need
      to reflect the diversity of these mechanisms.

PMID- 29218998
TI  - VKORC1-1639A allele influences warfarin maintenance dosage among Blacks receiving
      warfarin anticoagulation: a retrospective cohort study.
AB  - AIM: The study objectives were to investigate the association between selected
      CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or
      thrombotic risk, and to estimate mean daily maintenance dose of warfarin and
      international normalized ratio measurements among Blacks receiving warfarin
      anticoagulation. METHODS: We conducted a retrospective cohort study among 230
      Black adults receiving warfarin for a minimum of three consecutive months with a
      confirmed date of first dosage. RESULTS: A lower mean daily maintenance dosage of
      warfarin was required to maintain an international normalized ratio measurement
      within the therapeutic range among Blacks with the VKORC1-1639G>A variant alleles
      ([G/A vs G/G, p = 0.02], [A/A vs G/A, p = 0.008] and [A/A vs G/G, p = 0.001]).
      CONCLUSION: Data indicated that VKORC1-1639A variant allele influenced warfarin
      daily maintenance dosage among our small, likely admixed Black patient
      population.

PMID- 29218999
TI  - Study of Surface Wettability Change of Unconsolidated Sand Using Diffuse
      Reflectance Infrared Fourier Transform Spectroscopy and Thermogravimetric
      Analysis.
AB  - The effects exerted by the adsorption of vapors of a non-polar compound
      (deuterated benzene) and a polar compound (water) on the surface of Ottawa sand
      and a sample of reservoir sand (Channel), which was previously impregnated with
      silicon oil or two kinds of surfactants, (2-hydroxyethyl) trimethylammonium
      oleate (HETAO) and (2-hydroxyethyl)trimethylammonium azelate (HETAA), were
      studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)
      and thermogravimetric analysis (TGA). The surface chemistry of the sandstone
      rocks was elucidated by X-ray photoelectron spectroscopy (XPS) and scanning
      electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX).
      Terminal surface groups such as hydroxyls can strongly adsorb molecules that
      interact with these surface groups (surfactants), resulting in a wettability
      change. The wettability change effect suffered by the surface after treating it
      with surfactants was possible to be detected by the DRIFTS technique, wherein it
      was observed that the surface became more hydrophobic after being treated with
      silicon oil and HETAO; the surface became more hydrophilic after treating it with
      HETAA.

PMID- 29219000
TI  - Techniques for nothingness: Debate over the comparability of hypnosis and Zen in
      early-twentieth-century Japan.
AB  - This paper explores a debate that took place in Japan in the early twentieth
      century over the comparability of hypnosis and Zen. The debate was among the
      first exchanges between psychology and Buddhism in Japan, and it cast doubt on
      previous assumptions that a clear boundary existed between the two fields. In the
      debate, we find that contemporaries readily incorporated ideas from psychology
      and Buddhism to reconstruct the experiences and concepts of hypnosis and Buddhist
      nothingness. The resulting new theories and techniques of nothingness were fruits
      of a fairly fluid boundary between the two fields. The debate, moreover, reveals
      that psychology tried to address the challenges and possibilities posed by
      religious introspective meditation and intuitive experiences in a positive way.
      In the end, however, psychology no longer regarded them as viable experimental or
      psychotherapeutic tools but merely as particular subjective experiences to be
      investigated and explained.

PMID- 29219001
TI  - PI3K in cancer: its structure, activation modes and role in shaping tumor
      microenvironment.
AB  - The role of PI3K in cancer has been well established, and mutations of PIK3CA,
      the gene coding for catalytic subunit p110alpha of PI3K, are found in
      approximately 30% human cancers. The hyperactivated PI3K pathway plays a central
      role in the tumor cell activities such as proliferation, differentiation,
      chemotaxis, survival, trafficking and metabolism. Besides, PI3K pathway is
      involved in the regulation of angiogenesis and the host immune response against
      cancer. Therefore, the inhibition of PI3K pathway can yield multifaceted tumor
      cell-extrinsic effects that may synergize with chemotherapy, and more
      importantly, with the newly revived immunotherapy. Here, we review the structures
      and activation modes of PI3Ks and its implications in angiogenesis, extracellular
      matrix remodeling and tumor immunity.

PMID- 29219002
TI  - Relationship Between Personality Traits, Generativity, and Life Satisfaction in
      Individuals Attending University Programs for Seniors.
AB  - Personality traits of older adults and their contribution to life satisfaction
      and generative interest were assessed. A total of 342 older participants (66%
      women), mean age = 67.89 years old ( SD = 6.52, range = 55-84 years old), who
      attended the University of the Experience in Salamanca (Spain), were evaluated.
      Information on sociodemographic data, perceived health and activity, personality
      traits, generativity, and life satisfaction was collected using self-reported
      questionnaires. Results confirmed a relation between personality traits, life
      satisfaction, and generativity. In addition, generative concern, neuroticism,
      extraversion, agreeableness, and conscientiousness predicted life satisfaction at
      this stage. Moreover, the role of personality on generativity was confirmed.
      Individuals with interest and agreeableness toward others, who are organized,
      persistent, and motivated, are more predisposed to generativity. These results
      open the way to develop intervention programs that enhance positive personality
      traits and generative interest to improve quality of life of older people.

PMID- 29219003
TI  - The futile case of the aging ovary: is it mission impossible? A focused review.
AB  - Despite immense and impressive progress in the field of reproductive medicine,
      little has been achieved in terms of replenishing aged ovaries and improving
      their reproductive outcome. Age causes irreversible damage to human eggs in terms
      of quantity as well as quality. Nature probably designed women to reproduce best
      in their twenties and thirties. However, due to social, personal, career,
      educational and financial pressures, women delay pregnancies until their late
      thirties, by which time the chance of becoming pregnant is compromised by low
      fecundity rates and an increased risk of miscarriage. Age, unfortunately, is the
      most detrimental prognostic factor for success of fertility treatment. We have
      seen an increasing population of older women seeking fertility treatment. The
      existing evidence does not offer any clear-cut guidelines for the clinical
      handling of older women seeking fertility treatment. Various strategies have been
      tried to improve the fertility outcome of such women, but none has met with
      significant success. This review focuses on what can and what cannot be done in
      terms of improving fertility rates in older women.

PMID- 29219004
TI  - Predictors of malignancy in endometrial polyps: study of 421 women with
      postmenopausal bleeding.
AB  - OBJECTIVE: There is lack of consensus as whether benign-looking endometrial
      polyps should be removed in postmenopausal women. To help inform clinical
      practice, this study was conducted to quantify the prevalence and identify the
      predictors of hyperplasia and cancer in polyps. METHODS: The data of 2625
      consecutive women attending a postmenopausal bleeding clinic were collected
      prospectively in a UK teaching hospital between January 2011 and December 2015.
      Of them, 421 (16%) women with hysteroscopically benign-looking endometrial polyps
      with normal background endometrium were included. RESULTS: The number of women
      with benign polyps versus hyperplasia or cancer in polyps was 387 (92%) vs. 34
      (8%). The risk of hyperplasia and cancer in polyps was 5.5-fold and 3.5-fold
      higher in women with endometrial thickness >= 10.8 mm and in women with body mass
      index >= 32.5 kg/m2, respectively. Age, years since last period, ethnicity,
      recurrent postmenopausal bleeding, diabetes, hypertension, and the use of
      tamoxifen did not differ between the outcome groups. CONCLUSION: The prevalence
      of hyperplasia and cancer in benign-looking polyps is high. The independent
      predictors are body mass index and endometrial thickness. Removal of polyps may
      be warranted until hysteroscopic morphological criteria that can reliably predict
      the outcome are established in future research.

PMID- 29219005
TI  - Contemporary nationwide cardiology registers: Up-to-date registry data are
      required.

PMID- 29219006
TI  - Distribution and quantitative analysis of CIDEa and CIDEc in broiler chickens:
      accounting for differential fat deposition between strains.
AB  - 1. Differences in the expression of CIDEa and CIDEc in 20 different tissues were
      examined. Both CIDEa and CIDEc mRNA transcripts were predominantly but variably
      expressed in white adipose tissue (WAT) but were also expressed at moderate
      levels in the kidney and liver and at lower levels in the ovary. Interestingly,
      among WAT types, both CIDEa and CIDEc were expressed at the lowest levels in
      heart coronary WAT. 2. To better understand the roles of CIDEa and CIDEc in the
      fat deposition of broiler chickens, the differences in lipid droplet (LD) size
      and mRNA levels of CIDEa and CIDEc between lean-type and fat-type broiler chicken
      lines were studied. LD sizes were larger in fat-type broiler lines, and CIDEa and
      CIDEc mRNA levels in white adipose, kidney and liver tissues were significantly
      higher in fat-type broiler lines than in their lean counterparts. 3.
      Developmental expression patterns of CIDEa and CIDEc mRNA were analysed in
      different tissue types (WAT, liver and kidney) in Arbor Acres broiler chickens,
      and CIDEa and CIDEc mRNA expression levels increased during sequential
      developmental stages, achieving peak expression levels at week 6. 4. These
      observations suggest that the functions of CIDEa and CIDEc reflect inherent
      characteristics of lipid metabolism that contribute to the differences in fat
      deposition between strains. The results in this study contribute to a more robust
      understanding of the tissue distribution and expression patterns of CIDEa and
      CIDEc mRNA and facilitate further research concerning the molecular mechanism
      underlying fat deposition in broiler chickens.

PMID- 29219007
TI  - Anthropometric research of congenital auricular deformities for newborns.
AB  - OBJECTIVE: This study aimed to get the data of Neonatal auricle for helping
      pediatricians and obstetricians to make definite diagnosis and individualized
      treatment for newborn congenital auricular deformities in China. METHODS: A total
      of 1500 newborns' ears were evaluated in this study. Six surface measurements
      were performed directly on the auricles of the subjects as follows: physiognomic
      ear length and breadth, morphological ear length and breadth, cephalo-auricular
      distance, and cephalo otic angle. RESULTS: The incidence of neonatal auricular
      deformities in the Pearl River Delta area was 57.47% and the self-healing rate
      was 31.61% by the 30-day follow-up. There were significant differences between
      different types of auricular deformities (protruding ear, cup ear, lop ear,
      Stahl's ear, conchal crus, helical rim deformity, and composite deformity) and
      normal morphological differences of the auricle. CONCLUSIONS: Our findings
      suggested that individual differences in ear morphology are large and there were
      some differences between measurement data in our study and EarWell. Application
      of the EarWell system may lead to localized skin excoriations or breakdown as a
      result of mismatch with the ear. Therefore, early use of personalized ear molds
      produced by three-dimensional printing to determine if more deformed auricles may
      be corrected.

PMID- 29219008
TI  - Powered off-road wheelchair for the transportation of tetraplegics along mountain
      trails.
AB  - PURPOSE: For off-road mobility, some manual or power assisted devices were
      conceived to be self-driven by paraplegics while for tetraplegics non power
      assisted devices were conceived. These devices require one or more conductors who
      are subjected to a high physical demand thus potentially creating: precarious
      safety condition for the user an elevated physical demand of conductors could
      reduce the care and the attention to give to the user; the time of the outdoor
      adventure experience of the user could be limited. METHODS: To address these
      issues, an innovative user-centered power assisted off-road wheelchair for the
      transportation of tetraplegics along mountain trails was developed. The device,
      structured like a trike, is driven by two healthy conductors; the user is placed
      in the middle of the frame. A movable seat provides for the transfer from the
      standard to the off-road wheelchair. An electrical motor, powered by a battery
      pack, provides for the actuation. All the design and prototype aspects, the
      control system and experimental tests are detailed. RESULTS: The prototype
      satisfies mechanical, safety and duration requirements. No physical demand while
      using the device and for the transfer of the user to the device was identified.
      Fun and engaging tests were carried out and all the participants were involved.
      Implications for Rehabilitation The device has the potential to enhance the
      quality of life of tetraplegics in terms of new life experiences. The device
      revealed the real possibility of a full recreational experience, an enhanced
      participation and a better social integration of tetraplegics.

PMID- 29219009
TI  - MicroRNAs as potential prognosticators of neurological outcome in out-of-hospital
      cardiac arrest patients.
AB  - Out-of-hospital cardiac arrest survival rates have increased due to advancement
      in resuscitative measures, yet approximately 90% of survivors ultimately die or
      have severe neurologic dysfunction caused by ischemic injury. Currently, there
      are few early prognostic indicators of which patients have possibility of
      meaningful recovery. This leads to uncertainty for families and clinicians, as
      well as aggressive, invasive and expensive treatments despite medical futility.
      Several biomarkers investigated in traumatic brain injury have shown
      prognostication potential in ischemic brain injury. miRNAs, small noncoding RNAs
      responsible for gene regulation, have been studied in cardiovascular diseases,
      and have shown prognostication potential due to tissue specificity and stability
      in circulation. This review discusses available evidence on miRNAs
      prognosticating neurological outcomes after out-of-hospital cardiac arrest.

PMID- 29219011
TI  - Meconium aspiration syndrome: risk factors and predictors of severity.
AB  - PURPOSE: To identify risk factors and predictors of severity associated with
      meconium aspiration syndrome (MAS) in the patients admitted to the neonatal
      intensive care unit (NICU). MATERIALS AND METHODS: Retrospective study including
      newborns admitted, between 2005 and 2015, with a diagnosis of MAS. RESULTS: Of
      the newborns admitted to the NICU, 0.66% were diagnosed with MAS. These had
      higher prevalence of caesarean delivery (p < .001), nonreassuring or abnormal
      cardiotocography (CTG) (p < .001), intrapartum maternal fever (p = .002), Apgar
      scores at the first minute <7 (p < .001) and need of endotracheal intubation at
      birth (p < .001). Newborns with severe MAS had higher median reactive C protein
      (86.9 versus 9.65, p = .001) and 73.3% had pulmonary hypertension (p = .027).
      They required significantly more days of oxygen therapy, mechanical ventilation,
      nitric oxide, inotropic, and surfactant therapy, as well as longer hospital stay.
      CONCLUSIONS: Nonreassuring or abnormal CTG and low Apgar score at the first
      minute were established as risk factors for MAS and need of surfactant therapy as
      a predictor of severity.

PMID- 29219010
TI  - A review of mental health policies from Commonwealth countries.
AB  - BACKGROUND: The burden of disease related to mental disorders across the world is
      substantial. However, there remains inequality between funding for clinical and
      research activities between physical illness and mental illness in almost all
      countries. AIMS: One way of reducing this inequality is to ensure that mental
      health policies reflect this. We were interested in looking at the policies of
      members of Commonwealth. METHOD: We decided to survey 52 member countries of the
      Commonwealth to explore whether mental health policies existed and whether there
      was equity between physical and mental health services funding. Using World
      Health Organization (WHO) data sets and other sources when indicated, we looked
      at the existence and contents of mental health policies. RESULTS: We found that
      less than half of the countries had a mental health policy.
      Deinstitutionalization was not seen as a priority in many countries and there was
      no equity between physical and mental health funding. Although integration
      between physical and mental health care was recommended in many countries, there
      was a clear gap. CONCLUSION: It is apparent that there is still a long way to go
      in terms of equity between physical and mental health in terms of funding in
      member states of the Commonwealth. These findings confirm earlier observations of
      discrimination against people with mental illness. We suggest that there must be
      mechanisms in place to facilitate and support change wherever required.

PMID- 29219012
TI  - Significance of assay of nucleated RBCs in umbilical cord blood in neonates with
      meconium-stained amniotic fluid.
AB  - BACKGROUND: Approximately 8-15% of all infants are born with evidence of meconium
      stained amniotic fluid (MSAF). MSAF is a potentially serious sign of fetal
      compromise and may indicate fetal hypoxia Objectives and aim of the work: The
      present study was designed to evaluate the relationship between meconium stained
      amniotic fluid and fetal nucleated red blood cell counts. As well, we aim to
      evaluate the relationship between the presence of meconium in amniotic fluid and
      Apgar scores in neonates. SUBJECTS AND METHODS: A prospectively case-controlled
      study was performed on 40 women with clear amniotic fluid as control and 40 women
      with meconium-stained amniotic fluid as the study group. At delivery, 2 ml of
      umbilical cord blood was collected and analyzed for nucleated red blood cell
      (NRBC). RESULTS: The mean NRBC counts in meconium-stained amniotic fluid was
      significantly higher than the control group (18.35 +/- 7.7 and 9.6 +/- 4.96),
      respectively (p < .001). There were statistically significant differences
      concerning 1- and 5-min Apgar scores with lower values in the MSAF group (p <
      .001 and .001, respectively). CONCLUSION: Our results support previous studies
      which indicate the presence of meconium can be associated with chronic fetal
      hypoxia as demonstrated by elevated fetal NRBC levels.

PMID- 29219013
TI  - Author's response to Porter and Keefe letter to the editor regarding 'new
      frontiers in couple-based interventions in cancer care: refining the prescription
      for spousal communication'.

PMID- 29219014
TI  - Couple-based communication interventions for cancer: moving beyond a 'one size
      fits all' approach.

PMID- 29219015
TI  - Correction to: Zaleski et al. Guidelines of the Brazilian Association of Studies
      on Alcohol and Other Drugs (ABEAD) for diagnosis and treatment of psychiatric
      comorbidity with alcohol and other substance and dependence.

PMID- 29219016
TI  - Pembrolizumab in the treatment of advanced urothelial cancer.
AB  - Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase
      III trial KEYNOTE-045, pembrolizumab was associated with a significant overall
      survival benefit when compared with docetaxel, paclitaxel and vinflunine in
      second line metastatic urothelial carcinoma (UC). Additionally, in the first
      line, early results from an interim analysis of the Phase II trial Keynote-052
      study indicated that pembrolizumab is efficacious for cisplatin-ineligible
      patients. Based on data from these trials, pembrolizumab was the most recent
      among the five checkpoint inhibitors tested in UC to be approved by the US FDA in
      May 2017. It was granted regular approval for patients with advanced-stage UC who
      progress after receiving platinum-based chemotherapy and accelerated approval in
      the first line for patients who are ineligible to receive cisplatin.

PMID- 29219017
TI  - Eribulin in advanced breast cancer: safety, efficacy and new perspectives.
AB  - Eribulin is a synthetic analog of halichondrin B belonging to microtubule
      targeted agents with a distinct mechanism of inhibition of microtubule dynamics.
      This molecule has multiple nonmitotic effects on tumor biology, exhibiting
      effects on epithelial-mesenchimal transition and tumor vasculature. We review
      here preclinical and clinical studies on eribulin. The mitotic and nonmitotic
      effects together with its favorable safety profile make eribulin a unique drug
      with high potential in the treatment of metastatic breast cancer. The new
      emphasis of eribulin mechanism of action on vascular remodeling, microenvironment
      modifications and reversal of epithelial-mesenchimal transition paves the way to
      rethinking the use of the drug in an immunological perspective.

PMID- 29219018
TI  - Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation
      Study with Data from Center for Clinical and Basic Research and Osteoarthritis
      Initiative.
AB  - Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of
      the study was to investigate gender differences in contact area (CA) and
      congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different
      cohorts, quantified automatically from magnetic resonance imaging (MRI). Design
      The CA and CI markers were validated on 2 different data sets from Center for
      Clinical and Basic Research (CCBR) and Osteoarthritis Initiative (OAI). The CCBR
      cohort consisted of 159 subjects and the OAI subcohort consisted of 1,436
      subjects. From the MTF joint, the contact area was located and quantified using
      Euclidean distance transform. Furthermore, the CI was quantified over the contact
      area by assessing agreement of the first- and second-order general surface
      features. Then, the gender differences between CA and CI values were evaluated at
      different stages of radiographic OA. Results Female CAs were significantly higher
      than male CAs after normalization, male CIs were significantly higher than female
      CIs after correcting with age and body mass index ( P < 0.05), consistent across
      the 2 data sets. For the OAI data set, the gender differences were present at all
      stages of radiographic OA. Conclusion This study demonstrated the gender
      differences in CA and CI in MTF joints. The higher normalized CA and lower CI
      values in female knees may be linked with the increased risk of incidence of
      radiographic OA in females. These differences may help further understand the
      gender differences and/or to establish gender specific treatment strategies.

PMID- 29219019
TI  - Quantitative MRI of Human Cartilage In Vivo: Relationships with Arthroscopic
      Indentation Stiffness and Defect Severity.
AB  - Objective To investigate the association of cartilage defect severity, as
      determined by the International Cartilage Repair Society (ICRS) grading with
      indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI),
      a biomarker for the integrity of articular cartilage. Design Twenty-one patients
      scheduled for arthroscopic were included in the study. Prior to arthroscopy,
      subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation
      time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which
      also included ICRS grading and measurement of arthroscopic indentation stiffness.
      Arthroscopic evaluations and T2 mapping at anterior, central, and posterior
      medial and lateral femoral condyles were correlated using a colocalization
      scheme. Differences in Young's modulus, as derived by indentation tests, and T2
      times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis
      H tests. The correlation between modulus and T2 times was analyzed using
      Spearman's rank correlation coefficients. Results Modulus and T2 showed
      significant topographical variation. In the anterior region of interest (ROI) on
      the medial condyle the modulus showed a negative association with ICRS grade ( P
      = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and
      1 ( P = 0.047). Similar, but nonsignificant associations were found in the
      central ROI on the medial condyle. No significant correlations were observed
      between the indentation modulus and T2 times. Conclusions Cartilage degeneration
      is identified both with mechanical indentation and T2 mapping in MRI. However, in
      this study, indentation stiffness and T2 relaxation time in vivo, were not
      associated.

PMID- 29219020
TI  - Correlation of MRI Appearance of Autologous Chondrocyte Implantation in the Ankle
      with Clinical Outcome.
AB  - : The objective of this study was to characterize magnetic resonance imaging
      (MRI) findings and correlate with clinical results in patients who underwent
      autologous chondrocyte implantation (ACI) of osteochondral lesions of the talus
      (OLT). METHODS: Twenty-four grafts were evaluated at a mean 65.8 months after ACI
      for OLT. MRI was performed on a 1.5-T GE scanner using multiple sequences. Graft
      appearance was compared with preoperative MRI and evaluated for 6 criteria:
      defect fill, surface regularity, signal pattern, bone marrow edema, subchondral
      plate irregularity, and presence of cystic lesions. Clinical outcome was measured
      with the American Orthopaedic Foot and Ankle Society (AOFAS) clinical outcome
      score. RESULTS: Of 24 grafts, 22 (92%) demonstrated >75% defect fill. Eighteen
      (75%) had a mildly irregular and 6 (25%) had a moderately irregular articular
      surface. The signal pattern of the repair tissue was heterogenous in 23 (96%); 14
      (58%) layered and 9 (38%) mottled. Fourteen grafts (58%) showed decreased amount
      of bone marrow edema while 4 (17%) had no change and 5 (21%) had an increase in
      the amount of bone marrow edema. The subchondral bone plate was abnormal in most
      grafts, with focal defects seen in 10, slight depression in 7, and both in 5.
      Seven had an increase in cystic lesions while the others had no change, decrease
      or no cysts seen. Mean postoperative AOFAS score was 87.5 with mean improvement
      of 39.4. CONCLUSIONS: At 66-month mean follow-up, MRI appearance of the ACI
      grafts show imaging abnormalities but demonstrate good clinical results. While
      MRI is an important tool in the postoperative assessment of ACI grafts, the
      various variations from a normal/nonoperative ankle must be interpreted with
      caution.

PMID- 29219021
TI  - Review of the Mechanism of Action for Supartz FX in Knee Osteoarthritis.
AB  - Objective Summarize the biologic effects of Supartz FX for knee osteoarthritis
      (OA), the first worldwide clinically approved intra-articular (IA) hyaluronic
      acid (HA) product. Design To determine the mechanism of action from preclinical
      and clinical studies, a literature search was conducted of Supartz FX using
      academic databases from 1987 to 2016. Articles on Supartz FX that deal with its
      mechanisms of action were extracted, categorized, and reviewed. Results Supartz
      FX has 2 potential mechanisms of action: (1) biomechanical: IA Supartz FX
      directly improves the viscoelasticity and lubrication of synovial fluid; (2)
      physiologic: IA Supartz FX penetrates synovium and cartilage tissues to reach HA
      receptors on the surface of synoviocytes and chondrocytes. In synovium,
      suppression of gene expression in inflammatory mediators results in improved
      endogenous HA production, improved properties of synovial fluid, and reduction in
      pain. In cartilage, suppression of gene expression of collagenases and
      aggrecanases suppresses cartilage degeneration. Conclusion The net results of
      basic and clinical studies is that IA Supartz FX provides a more favorable
      biomechanical and functional environment in the knee joint. Hence, it is not only
      a lubricant but is also physiologically active. These actions may help explain
      both short- and long-term improvement in pain and function often achieved from IA
      Supartz FX in knee OA.

PMID- 29219022
TI  - Effectiveness of Radiofrequency Hyperthermia for Treating Cartilage in Guinea
      Pigs with Primary Osteoarthritis.
AB  - Objective Autophagy was reported to be essential for maintaining chondrocyte
      function, and reduced autophagy leads to osteoarthritis (OA). Previous studies
      showed involvement of heat shock stress in the control of autophagy in cells.
      This study sought to investigate the effect of hyperthermia on the expression of
      autophagy-related proteins in articular cartilage and the progression of
      naturally occurring OA in Hartley guinea pigs. Design Radiofrequency pulses of
      13.56 MHz were applied to the animals' knees for 20 minutes to induce
      hyperthermia. The knee joints were resected at 8 hours, 24 hours, 72 hours, 7
      days, and 6 months after hyperthermia. Serial sections of knees were examined for
      histopathological changes. The expression levels of Unc-51-like kinase 1 (ULK1)
      and Beclin1 were analyzed by immunohistochemistry. Results Analysis of the
      distribution of positive cells showed that, in cases of moderate OA, ULK1 and
      Beclin1 expression levels were significantly decreased in the superficial zone
      (SZ) and middle zone (MZ) ( P < 0.01) compared with normal cartilage. Seven days
      after exposure to radiofrequency waves, expression levels of ULK1 and Beclin1
      were augmented in the SZ in animals with mild OA. The severity of cartilage
      degradation was significantly reduced ( P < 0.01) in the radiofrequency-treated
      knees versus the untreated knees. Conclusions This study showed that heat
      stimulation enhanced autophagy in healthy knee chondrocytes and chondrocytes in
      knees with mild OA. The study also showed that long-term periodic application of
      hyperthermia suppresses aging-related progression of OA. The activation of
      autophagy by radiofrequency hyperthermia may be an effective therapeutic approach
      for osteoarthritis.

PMID- 29219023
TI  - Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis
      Models.
AB  - Objective The objective of this study was to determine whether intra-articular
      injections of tenascin-C (TNC) could prevent cartilage damage in murine models of
      osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee
      joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4
      weeks postinjection. To investigate the effects of TNC on cartilage degeneration
      after surgery to knee joints, articular spaces were filled with 100 MUg/mL (group
      I), 10 MUg/mL (group II) of TNC solution, or control (group III). TNC solution of
      10 MUg/mL was additionally injected twice after 3 weeks (group IV) or weekly
      after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically
      assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks
      after surgery. Results Exogenous TNC was maintained in the cartilage and synovium
      for 1 week after administration. Histological scores in groups I and II were
      better than scores in group III at 4 and 6 weeks, but progressive cartilage
      damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections
      (groups IV and V) showed significantly better Mankin score than single injection
      (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the
      cartilage of knee joints for 1 week, and could decelerate articular cartilage
      degeneration in murine models of OA. We also showed that sequential
      administration of TNC was more effective than a single injection. TNC could be an
      important molecule for prevention of articular cartilage damage.

PMID- 29219024
TI  - Excess Maternal Thyroxine Alters the Proliferative Activity and Angiogenic
      Profile of Growth Cartilage of Rats at Birth and Weaning.
AB  - Objective The aim of this study was to unravel the mechanisms by which thyroxine
      affects skeletal growth by evaluating proliferative activity and angiogenic
      profile of growth cartilage of neonatal and weanling rats. Methods Sixteen adult
      Wistar rats were equally divided into 2 groups: control and treated with
      thyroxine during pregnancy and lactation. The weight, measurement of plasma free
      T4 and thyroids, femurs' histomorphometric analysis, and proliferative activity
      and angiogenic profile by immunohistochemical or real-time reverse transcriptase
      polymerase chain reaction in growth cartilage was performed. Data were analyzed
      using Student's t test. Results The free T4 was significantly higher in the
      treated rats. However, the height of the follicular epithelium of the thyroid in
      newborns was significantly lower in the treated group. The excess maternal
      thyroxine significantly reduced the body weight and length of the femur in the
      offspring but significantly increased the thickness of trabecular bone and
      changed the height of the zones of the growth plate. Furthermore, excess maternal
      thyroxine reduced cell proliferation and vascular endothelial growth factor
      (VEGF) expression in the growth cartilage of newborn and 20-day-old rats ( P <
      0.05). There was also a reduction in the immunohistochemical expression of Tie2
      in the cartilaginous epiphysis of the newborns and FLK-1 in the articular
      cartilage of 20-day-old rats. No significant difference was observed in Ang2
      expression. Conclusions The excess maternal thyroxine during pregnancy and
      lactation reduced endochondral bone growth in the progeny and reduced the
      proliferation rate and VEGF, Flk-1, and Tie2 expression in the cartilage of
      growing rats without altering the mRNA expression of Ang1 and Ang2.

PMID- 29219026
TI  - Improving long-term outcomes of acute cardiovascular syndromes.

PMID- 29219025
TI  - The Effect of Growth Hormone on Chondral Defect Repair.
AB  - Objective Focal chondral defects alter joint mechanics and cause pain and
      debilitation. Microfracture is a surgical technique used to treat such defects.
      This technique involves penetration of subchondral bone to release progenitor
      cells and growth factors from the marrow to promote cartilage regeneration. Often
      this results in fibrocartilage formation rather than structured hyaline
      cartilage. Some reports have suggested use of growth hormone (GH) with
      microfracture to augment cartilage regeneration. Our objective was to test
      whether intra-articular (IA) GH in conjunction with microfracture, improves
      cartilage repair in a rabbit chondral defect model. We hypothesized that GH would
      exhibit a dose-dependent improvement in regeneration. Design Sixteen New Zealand
      white rabbits received bilateral femoral chondral defects and standardized
      microfracture repair. One group of animals ( n = 8) received low-dose GH by IA
      injection in the left knee, and the other group ( n = 8) received high-dose GH in
      the same manner. All animals received IA injection of saline in the contralateral
      knee as control. Serum assays, macroscopic grading, and histological analyses
      were used to assess any improvements in cartilage repair. Results Peripheral
      serum GH was not elevated postoperatively ( P = 0.21). There was no improvement
      in macroscopic grading scores among either of the GH dosages ( P = 0.83). Scoring
      of safranin-O-stained sections showed no improvement in cartilage regeneration
      and some evidence of increased bone formation in the GH-treated knees.
      Conclusions Treatment with either low- or high-dose IA GH does not appear to
      enhance short-term repair in a rabbit chondral defect model.

PMID- 29219027
TI  - Effectiveness of psycho-educational interventions with telecommunication
      technologies on emotional distress and quality of life of adult cancer patients:
      a systematic review.
AB  - PURPOSE: To provide a comprehensive review of psycho-educational interventions
      using telecommunication technologies developed for adult cancer patients,
      assessing their effectiveness in reducing emotional distress and improving
      quality of life (QoL). MATERIALS AND METHODS: A narrative approach was used for
      extraction and synthesis of the data. Relevant studies were identified through
      the electronic databases PubMed, Scopus, Web of Science, ProQuest, Psychology &
      Behavioral Sciences Collection (through EBSCOhost), and CENTRAL. RESULTS: Eight
      studies involving 1016 participants met inclusion criteria. The majority of the
      studies included (n = 6) used a randomized design and were published between 2007
      and 2016. Interventions used a variety of delivery resources, such as telephone,
      e-mail and websites, but all were aiming to respond to information needs and
      develop stress control skills. A trend toward reducing distress and improving QoL
      was found, but estimated effect sizes were typically small (d < 0.5).
      Telephonically delivered psycho-educational interventions presented the highest
      between-group effects on these outcomes during survival, but were limited by
      sample size. CONCLUSIONS: The efficacy of interventions using distance approaches
      in the cancer setting is still not well-established. Further research should be
      conducted through well-designed studies with more interactive features that
      minimize the lack of face-to-face interaction. Implications for rehabilitation
      Rehabilitation professionals working in the field of oncology should invest in
      the development of psycho-educational interventions responding the patients'
      educational needs and promoting their stress control skills. Programs using
      telecommunications technologies may reduce disparities in service delivery within
      this setting, minimizing geographic and socio-economic barriers to engagement in
      the interventions. With the current technological development, it is possible to
      perform more interactive interventions that stimulate therapist-patient
      interactions. However, available protocols in this field still employ basic
      resources (e.g., websites, e-mail, and videos). Young adult cancer patients are
      exposed to additional requirements related to fertility and parenthood. New
      intervention approaches should consider their informational needs.

PMID- 29219028
TI  - Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood
      flow in older adults.
AB  - Ambulatory blood pressure (ABP) reflects the end-organ vascular stress in daily
      life; however, its influence on brain neuronal fiber integrity and cerebral blood
      flow (CBF) remains unclear. The objective of this study was to determine the
      associations among ABP, white matter (WM) neuronal fiber integrity, and CBF in
      older adults. We tested 144 participants via ABP monitoring and diffusion tensor
      imaging. The total level and pulsatile indices of CBF were measured by phase
      contrast MRI and transcranial Doppler, respectively. Neuropsychological
      assessment was conducted in 72 participants. Among ambulatory and office BP
      measures, elevated 24-h pulse pressure (PP) was associated with the greatest
      number of WM skeleton voxels with decreased fractional anisotropy (FA) and
      increased mean diffusivity (MD). Furthermore, these associations remained
      significant after adjusting for age, antihypertensive use, aortic stiffness, WM
      lesion volume, and office PP. Radial diffusivity (RD) was elevated in the regions
      with decreased FA, while axial diffusivity was unaltered. The reduction in
      diastolic index explained a significant proportion of the individual variability
      in FA, MD, and RD. Executive function performance was correlated with WM fiber
      integrity. These findings suggest that elevated ambulatory PP may deteriorate
      brain neuronal fiber integrity via reduction in diastolic index.

PMID- 29219029
TI  - Determination of Stent Frame Displacement After Endovascular Aneurysm Sealing.
AB  - PURPOSE: To describe and validate a new methodology for visualizing and
      quantifying 3-dimensional (3D) displacement of the stent frames of the Nellix
      endosystem after endovascular aneurysm sealing (EVAS). METHODS: The 3D positions
      of the stent frames were registered to 5 fixed anatomical landmarks on the post
      EVAS computed tomography (CT) scans, facilitating comparison of the position and
      shape of the stent frames between consecutive follow-up scans. Displacement of
      the proximal and distal ends of the stent frames, the entire stent frame
      trajectories, as well as changes in distance between the stent frames were
      determined for 6 patients with >5-mm displacement and 6 patients with <5-mm
      displacement at 1-year follow-up. The measurements were performed by 2
      independent observers; the intraclass correlation coefficient (ICC) was used to
      determine interobserver variability. RESULTS: Three types of displacement were
      identified: displacement of the proximal and/or distal end of the stent frames,
      lateral displacement of one or both stent frames, and stent frame buckling. The
      ICC ranged from good (0.750) to excellent (0.958). No endoleak or migration was
      detected in the 12 patients on conventional CT angiography at 1 year. However, of
      the 6 patients with >5-mm displacement on the 1-year CT as determined by the new
      methodology, 2 went on to develop a type Ia endoleak in longer follow-up, and
      displacement progressed to >15 mm for 2 other patients. No endoleak or
      progressive displacement was appreciated for the patients with <5-mm
      displacement. CONCLUSION: The sac anchoring principle of the Nellix endosystem
      may result in several types of displacement that have not been observed during
      surveillance of regular endovascular aneurysm repairs. The presented methodology
      allows precise 3D determination of the Nellix endosystems and can detect subtle
      displacement better than standard CT angiography. Displacement >5 mm on the 1
      year CT scans reconstructed with the new methodology may forecast impaired
      sealing and anchoring of the Nellix endosystem.

PMID- 29219030
TI  - Laser Atherectomy Combined With Drug-Coated Balloon Angioplasty Is Associated
      With Improved 1-Year Outcomes for Treatment of Femoropopliteal In-Stent
      Restenosis.
AB  - PURPOSE: To examine whether laser atherectomy combined with drug-coated balloons
      (laser + DCB) can improve the outcomes of femoropopliteal (FP) in-stent
      restenosis (ISR). METHODS: A dual-center retrospective study was conducted of 112
      consecutive patients (mean age 70.3+/-10.6 years; 86 men) with Tosaka class II
      (n=29; diffuse stenosis) or III (n=83; occlusion) FP-ISR lesions. Sixty-two
      patients (mean age 68.5+/-10 years; 51 men) underwent laser + DCB while the other
      50 patients (mean age 72.5+/-10.8 years; 35 men) had laser atherectomy plus
      balloon angioplasty (laser + BA). Critical limb ischemia was the indication in
      33% of the interventions. The average lesion length was 247 mm. A Cox regression
      hazard model was developed to examine the association between laser + DCB vs
      laser + BA; the results are presented as the hazard ratio (HR) and 95% confidence
      interval (CI). One-year target lesion revascularization (TLR) and reocclusion
      were estimated using the Kaplan-Meier method. RESULTS: Overall procedure success
      was 98% and was similar between groups. Bailout stenting was less often required
      in the laser + DCB group (31.7% vs 58%, p=0.006). The combination of laser + DCB
      was associated with improved 12-month estimates for freedom from TLR (72.5% vs
      50.5%, p=0.043) and freedom from reocclusion (86.7% vs 56.9%, p=0.003). Among
      patients with Tosaka III FP-ISR, combination therapy with laser + DCB was also
      associated with increased freedom from reocclusion (87.1% vs 57.1%, p=0. 028). On
      multivariable analysis, treatment with laser + DCB was associated with a
      significantly reduced risk of reocclusion (HR 0.08, 95% CI 0.17 to 0.38;
      p=0.002). CONCLUSION: When used for treatment of complex FP-ISR lesions, DCB
      angioplasty combined with laser atherectomy is associated with significantly
      reduced 1-year TLR and reocclusion rates.

PMID- 29219031
TI  - The role of community pharmacists in the identification and ongoing management of
      women at risk for perinatal depression: A qualitative study.
AB  - BACKGROUND: While pharmacists are among the most accessible primary health
      professionals within a mother's healthcare team to identify potential cases of
      perinatal depression (PND), very little in the literature suggests that this role
      has been explored. AIM: The aim of this study was to explore community
      pharmacists' perspectives on their potential roles in perinatal mental health
      promotion (recognition and health education) and the factors affecting these
      roles. METHODS: In total, 20 semi-structured, in-depth interviews were conducted
      with community pharmacists. RESULTS: Most pharmacists highlighted their
      significant roles in recognising PND symptoms and providing medication-related
      support to perinatal mothers. Barriers to service provision included inter
      professional role boundaries, the lack of established referral systems and
      service remuneration and the lack of adequate training in mental health.
      CONCLUSION: Pharmacists could potentially reinforce their involvement in mental
      health promotion activities.

PMID- 29219032
TI  - Corrigendum.
AB  - Corrigendum to "Change in perception of sclerotherapy results after exposure to
      pre-post intervention photographs" by Fabricio R Santiago, Mario Piscoya, Yung
      Wei Chi. The article was first published online, 23 October 2017
      https://doi.org/10.1177/0268355517736178 . The authors wish to notify readers of
      the following change: In page 1 - "abstract", Line 32 - "Results," in the
      sentence: "Individuals were more satisfied with the results of sclerotherapy
      after exposure to images portraying their limbs two months before the procedure
      (p < 0.0028)," the word before in "portraying their limbs two months before"
      should be replaced with after, this ensures that the results make sense. The
      correct sentence should read, "Individuals were more satisfied with the results
      of sclerotherapy after exposure to images portraying their limbs two months after
      the procedure (p < 0.0028)." Subsequent versions of the article will be
      corrected.

PMID- 29219033
TI  - Complex Relationships Among Masculine Norms and Health/Well-Being Outcomes:
      Correlation Patterns of the Conformity to Masculine Norms Inventory Subscales.
AB  - The Conformity to Masculine Norms Inventory (CMNI) is a widely used
      multidimensional scale. Studies using the CMNI most often report only total scale
      scores, which are predominantly associated with negative outcomes. Various
      studies since the CMNI's inception in 2003 using subscales have reported both
      positive and negative outcomes. The current content analysis examined studies ( N
      = 17) correlating the 11 subscales with 63 criterion variables across 7
      categories. Most findings were consistent with past research using total scale
      scores that reported negative outcomes. For example, conformity to masculine
      norms has been inversely related to help-seeking and positively correlated with
      concerning health variables, such as substance use. Nonetheless, past reliance on
      total scores has obscured the complexity of associations with the CMNI in that
      30% of the findings in the present study reflected positive outcomes,
      particularly for health promotion. Subscales differed in their relationships with
      various outcomes: for one subscale they were predominantly positive, but six
      others were mostly negative. The situational and contextual implications of
      conformity to masculine norms and their relationships to positive and negative
      outcomes are discussed.

PMID- 29219034
TI  - Measuring Relative Coupling Strength in Circadian Systems.
AB  - Modern imaging techniques allow the monitoring of circadian rhythms of single
      cells. Coupling between these single cellular circadian oscillators can generate
      coherent periodic signals on the tissue level that subsequently orchestrate
      physiological outputs. The strength of coupling in such systems of oscillators is
      often unclear. In particular, effects on coupling strength by varying cell
      densities, by knockouts, and by inhibitor applications are debated. In this
      study, we suggest to quantify the relative coupling strength via analyzing
      period, phase, and amplitude distributions in ensembles of individual circadian
      oscillators. Simulations of different oscillator networks show that period and
      phase distributions become narrower with increasing coupling strength. Moreover,
      amplitudes can increase due to resonance effects. Variances of periods and phases
      decay monotonically with coupling strength, and can serve therefore as measures
      of relative coupling strength. Our theoretical predictions are confirmed by
      studying recently published experimental data from PERIOD2 expression in slices
      of the suprachiasmatic nucleus during and after the application of tetrodotoxin
      (TTX). On analyzing the corresponding period, phase, and amplitude distributions,
      we can show that treatment with TTX can be associated with a reduced coupling
      strength in the system of coupled oscillators. Analysis of an oscillator network
      derived directly from the data confirms our conclusions. We suggest that our
      approach is also applicable to quantify coupling in fibroblast cultures and
      hepatocyte networks, and for social synchronization of circadian rhythmicity in
      rodents, flies, and bees.

PMID- 29219035
TI  - Effect of repeated application of pendimethalin on its persistence and
      dissipation kinetics in soil under field and laboratory conditions.
AB  - The repeated application of herbicide can alter its persistence in the
      environment. In India, wheat fields are exposed to herbicide application at least
      once in the cropping season. The present study investigated the dissipation
      behavior of pendimethalin applied annually to a wheat field over four cropping
      seasons from 2012 to 2016. The dissipation studies were also conducted under
      laboratory conditions during 2015-2016. Pendimethalin from soil and wheat grain
      samples was extracted using matrix solid-phase dispersion and quantified using
      high-performance liquid chromatography and gas chromatography-tandem mass
      spectrometry. The average recoveries of pendimethalin from soil and crop produce
      ranged from 81.3% to 103.1%. The half-life of pendimethalin ranged from 20.9 to
      31.3 days and 9.4 to 60.2 days under field and laboratory conditions,
      respectively. Dissipation of pendimethalin varied significantly over the years
      under field conditions and was comparatively faster than under laboratory
      conditions. On the other hand, non-significant variation in the dissipation of
      pendimethalin in soils under laboratory conditions was observed. The residues of
      pendimethalin in crop produce at harvest were below the maximum residue limit set
      by EPA.

PMID- 29219036
TI  - Head Movements During Visual Orienting Toward Moving Prey in the Lizard
      Takydromus tachydromoides.
AB  - It is important to investigate visual orienting in reptiles to better understand
      the basic organization of the oculomotor system in vertebrates. However,
      quantitative analyses of visual orienting behavior in reptiles have rarely been
      conducted, except in chameleons. In the present study, we videorecorded the head
      and body movements of the lizard Takydromus tachydromoides during visual tracking
      of moving prey and analyzed them frame-by-frame. Before approaching prey, visual
      tracking mainly consisted of brief intermittent turns of the head (saccade).
      After the head saccades, the angular position of the prey relative to the lizard
      head was kept at 10-70 degrees  (laterally) in most cases, rather than at 0
      degrees  (in front). In addition, the ratio of the amplitude of the head saccades
      to prey position was 0.2-0.3, which is much smaller than 1, suggesting that the
      head did not orient exactly toward the prey after most saccades. These results
      were observed under both white (homogeneous) and grating (structured)
      backgrounds. Possible functions of head saccades in the lizard are discussed.

PMID- 29219037
TI  - Burrow Morphology of Alpheid Shrimps: Case Study of Alpheus brevicristatus and a
      Review of the Genus.
AB  - The Alpheus brevicristatus De Haan, 1844 is one of the commonest shrimp species
      inhabiting the tidal flats in Japan. This species is sometimes accompanied by the
      facultative symbiotic goby, Acentrogobius spp. Here, we investigated the burrow
      morphology of A. brevicristatus in a tidal flat of Uranouchi Inlet, Kochi
      Prefecture, Japan. We also reviewed existing literature on alpheid burrow
      morphology using the resin casting technique, to determine how burrows vary in
      the presence and absence of gobies. Nine burrows were casted in situ using
      polyester resin. All burrows were long, but shallow in structure, with several
      funnel-shaped openings and short cul-de-sac branches. This species appears to use
      several burrow openings to access the sediment surface for feeding with high
      efficiency. Gobies were not associated with all burrows cast; however, 1-3
      individuals of the small alpheid shrimp Athanas japonicus Kubo, 1936 were
      entombed in seven of the casts. A review of 12 studies on the burrow morphology
      of 16 Alpheus species based on resin casting techniques showed wide variation in
      burrow characteristics, such as burrow depth, length, and number of openings. Our
      findings suggest that burrow structure is influenced by species-specific
      characteristics and sediment type. The possibility that the presence of the
      symbiotic goby affects the burrow morphology of Alpheus shrimp is discussed.

PMID- 29219038
TI  - Duplication and Variation in the Major Histocompatibility Complex Genes in
      Blakiston's Fish Owl, Bubo blakistoni.
AB  - The major histocompatibility complex (MHC) includes many genes that are essential
      for the adaptive immune system, and variation in the antigen binding site (ABS)
      is related to resistance against pathogens. In the present study, quantitative
      real-time PCR indicated a larger number of MHC gene copies in the endangered
      population of Blakiston's fish owl (Bubo blakistoni) than in five other owl
      species, and massively parallel pyrosequencing detected more MHC class IIbeta per
      individual alleles in B. blakistoni than in the other species. A chromosomal
      fluorescence in situ hybridization (FISH) analysis showed that the MHC class I
      and class IIbeta loci are closely linked on a single pair of microchromosomes,
      indicating that the MHC genes were tandemly duplicated in a limited chromosomal
      region. Because B. blakistoni has twice as many MHC genes as its sister species,
      the tawny fish owl (Bubo flavipes), the duplication of MHC genes occurred after
      these species diverged by speciation. A Bayesian molecular phylogenetic analysis
      showed that the DAB1 and DAB2 lineages of MHC class IIbeta alleles from various
      strigid species each formed a separate clade, indicating that the two allelic
      lineages preceded the radiation of Strigidae and evolved as paralogs. By
      contrast, the ABS sequences did not form distinct clades between DAB1 and DAB2
      alleles but were intermixed, presumably due to gene conversion. Despite the low
      diversity of alleles per locus, B. blakistoni had many lineages of MHC class
      IIbeta alleles. Gene duplication increases variation in the MHC genes in this
      species, and could have facilitated adaptation in small populations.

PMID- 29219039
TI  - Morphogenesis and Mucus Production of Epithelial Tissues of Three Major Salivary
      Glands of Embryonic Mouse in 3D Culture.
AB  - Embryonic mouse submandibular epithelia initiate branching morphogenesis within
      two days when embedded in Matrigel and stimulated by members of the epidermal
      growth factor family. However, it is unknown whether the end buds further branch
      over longer culture periods, and whether saliva-producing cells differentiate
      there. In the present study, we cultivated three major (submandibular, sublingual
      and parotid) salivary epithelia from 13-day embryos for 14 days in mesenchyme
      free cultures. All epithelia continued to grow and branch to form numerous acinus
      like structures in medium supplemented with neuregulin 1, fibroblast growth
      factor 1, and insulintransferrin-sodium selenite. Alcian blue staining to detect
      mucous cells showed that each epithelium differentiated via three distinct modes,
      as seen in normal development, although the staining intensities were weaker than
      in normal development. RT-PCR analysis of the amylase gene showed that no
      epithelia expressed amylase after 14 days of culture, which is inconsistent with
      the fact that only parotid epithelium does so at postnatal day 7 during normal
      development. These results suggest that cytodifferentiation progresses to a
      lesser extent in mesenchyme-free cultures than in vivo.

PMID- 29219040
TI  - Taxonomic Relationships of Hynobius stejnegeri and H. yatsui, with Description of
      the Amber-Colored Salamander from Kyushu, Japan (Amphibia: Caudata).
AB  - Examination of the holotype of Hynobius stejnegeri Dunn, 1923 revealed that the
      species is identical with H. yatsui Oyama, 1947 , recently resurrected from H.
      naevius (Temminck and Schlegel, 1838). The name H. yatsui is therefore relegated
      to a subjective junior synonym of H. stejnegeri. The latter name, however, has
      been widely applied to an amber-colored or tortoise-shell salamander from Kyushu,
      southwestern Japan, which now requires a new name. We, thus, describe the
      ambercolored salamander as a new species Hynobius ikioi. The new species is
      phylogenetically very close to H. amakusaensis Nishikawa and Matsui, 2014 and H.
      osumiensis Nishikawa and Matsui, 2014 , both also from Kyushu, but is easily
      distinguished from them by its uniquely bi-colored dorsum.

PMID- 29219041
TI  - Potential Causative Mutation for Melanism in Rats Identified in the Agouti
      Signaling Protein Gene (Asip) of the Rattus rattus Species Complex on Okinawa
      Island, Japan.
AB  - The occurrence of black fur, or melanism, in many mammalian species is known to
      be linked to DNA sequence variation in the agouti signaling protein (Asip) gene,
      which is a major determinant of eumelanin and pheomelanin pigments in coat color.
      We investigated 38 agouti (i.e., banded wildtype) and four melanistic Rattus
      rattus species complex (RrC) lineage II specimens from Okinawa Island, Ryukyu
      Islands, Japan, for genetic variation in three exons and associated flanking
      regions in the Asip gene. On Okinawa, a predicted loss-of-function mutation
      caused by a cysteine to serine amino acid change at p.124C>S (c.370T>A) in the
      highly conserved functional domain of Asip was found in melanistic rats, but was
      absent in agouti specimens, suggesting that the p.124C>S mutation is responsible
      for the observed melanism. Phylogeographic analysis found that Asip sequences
      from Okinawan RrC lineage II, including both agouti and melanistic specimens,
      differed from: 1) both agouti and melanistic RrC lineage I from Otaru, Hokkaido,
      Japan, and 2) agouti RrC lineages I and II from South Australia. This suggests
      the possibility of in-situ mutation of the Asip gene, either within the RrC
      lineage II population on Okinawa or in an unsampled RrC lineage II population
      with biogeographic links to Okinawa, although incomplete lineage sorting could
      not be ruled out.

PMID- 29219042
TI  - Context-Dependent Passive Avoidance Learning in the Terrestrial Slug Limax.
AB  - The terrestrial slug Limax has been used as a model animal for studying the
      neural mechanisms underlying associative olfactory learning. The slug also
      innately exhibits negative phototactic behavior using its eyes. In the present
      study, we developed an experimental paradigm for quantification of slug's
      negative phototaxis behavior, and investigated whether the nature of the negative
      phototaxis can be modified by learning experience. The experimental set-up
      consists of light and dark compartments, between which the slug can move freely.
      During conditioning, the slug was placed in the light compartment, and an
      aversive stimulus (quinidine sulfate solution) was applied when it reached the
      dark compartment. After a single conditioning session, the time to reach the dark
      compartment significantly increased when it was tested following 24 hr or one
      week. Protein synthesis inhibition immediately following the conditioning
      impaired the memory retention at one week but not at 24 hr. The retrieval of the
      memory was context-dependent, as the time to reach the dark compartment did not
      significantly increase if the slug was placed on a floor with a different texture
      in the memory retention test. If the aversive stimulus was applied when the slug
      was in the light compartment, the time to reach the dark compartment did not
      increase after 24 hr. This is the first report demonstrating the capability of
      the slug to form context-dependent passive avoidance memory that can be
      established in a single conditioning session.

PMID- 29219043
TI  - Changes in Mate Preferences by Female Guppies: Effects of Male Phenotypes and
      Female Age.
AB  - In recent decades, variation in female preferences within a species has attracted
      considerable attention. However, how female individuals in most species change
      their mate preferences remain unclear. In this study, we examined the change in
      mate preferences in female individuals of the guppy, Poecilia reticulata. This
      was done by exposing naive, virgin females to two male groups differing in the
      abundance of ornamented males over a period of seven days. The male-exposure
      treatment groups consisted of (1) primarily males with large orange spots and (2)
      primarily males with small orange spots. Following each treatment, we measured
      female preference for brightly colored males with large orange spots, using a
      pair of digitally modified male images differing in orange spot patterns. Our
      results indicated that the patterns of change in mate preferences differed
      between young and old females. After exposure to primarily males with large
      orange spots, young females were more attracted to the male images overall and
      showed a preference for the bright male image. Specifically, young females showed
      a stronger preference for the bright male image when they had been exposed to
      male groups in which the among-male difference in orange spot patterns was
      greater. However, in old females, both male-exposure treatments and order of the
      treatments affected their mate preferences. These results suggest that social
      components, i.e., both the abundance of ornamented males and the age structure of
      females in a population, influence the direction and intensity of sexual
      selection.

PMID- 29219044
TI  - Differential Responses of Two Ecologically Similar Case-Bearing Caddisfly Species
      to a Fish Chemical Cue: Implications for a Coexistence Mechanism.
AB  - The mechanisms for the coexistence of multiple species occupying the same
      ecological niche are often puzzling. Predator effects on competitively superior
      species is one possible mechanism. In this study, we tested whether the presence
      of size-selective predators (fishes) acts as a mechanism for the coexistence of
      two species of case-bearing caddisfly larvae, Perissoneura paradoxa and
      Psilotreta kisoensis (Odontoceridae, Trichoptera). The larvae of these two
      species have similar ecological and life history traits except their body size,
      and they have been found to coexist only in habitats shared with predatory
      fishes. Experiments on intra and interspecific competition revealed that the
      larger Pe. paradoxa always outcompeted the smaller Ps. kisoensis in the absence
      of predatory fishes, suggesting that Pe. paradoxa performed intra-guild predation
      on Ps. kisoensis. We also conducted experiments to examine how strongly each of
      these species responded in terms of case repair with/without a predator chemical
      cue after their cases were partly dismantled. Perissoneura paradoxa exhibited a
      stronger case repair response in the presence of a predator chemical cue than
      that exhibited by Ps. kisoensis, suggesting that Pe. paradoxa is more vulnerable
      to fish predation, probably because their body size is in the preferred prey
      range of fishes. We suggest that the presence of predators works in the favor of
      smaller, subordinate species through size-selective predator effects, enabling
      these two competitive species to coexist in the same habitat.

PMID- 29219045
TI  - Mitochondrial Genetic Diversity and Phylogeography of Mus musculus castaneus in
      Northern Punjab, Pakistan.
AB  - Regions of Iran, Afghanistan, Pakistan and northwestern India have been proposed
      as the place of origin of Mus musculus castaneus. But despite the fact that
      Pakistan encompasses an important part of its range, M. m. castaneus populations
      in Pakistan have not been the subject of intensive genetic and biogeographic
      studies, except for a very small number of samples included in past studies. We
      studied genetic variation in M. m. castaneus (CAS) from northern Punjab Province,
      Pakistan, by using cytochrome b (Cytb) analysis in a sample of 98 individuals.
      Median-joining network revealed four well differentiated CAS sub-lineages
      coexisting within a small geographical region; these had previously been thought
      to have largely non-overlapping geographic distributions. Moreover, haplotypes
      from Pakistan occupied a central position in the network and all identified
      global haplotypes were also present in Pakistan. All identified CAS sub-lineages
      proved to be highly diverse on the basis of haplotype and nucleotide diversity
      indices. Tajima's D test and Fu's Fs tests of neutrality suggest recent
      population expansions in all sub-lineages. Expansion times were estimated as
      21,760-134,930, 10,800-64,400 and 4950-30,665 ybp using substitution rates of
      2.5%, 5% and 11%, respectively. Our results support the hypothesis that northern
      Punjab Province in Pakistan is the most likely source area for M. m. castaneus,
      and that the CAS sub-lineages in this region have undergone rapid population
      expansion events at different time periods, which appear to have benefitted from
      human-mediated transport, although one of them clearly predates the establishment
      of human settlements in this region.

PMID- 29219046
TI  - Molecular Cloning and Functional Characterization of Antimicrobial Peptides
      Brevinin-1ULf and Ulmin-1ULa in the Skin of the Newly Classified Ryukyu Brown
      Frog Rana ulma.
AB  - Antimicrobial peptides (AMPs) were previously isolated from the skin of the
      Ryukyu brown frog Rana okinavana. However, this species has recently been
      reclassified as two species, i.e., Rana kobai and Rana ulma. As a result, it was
      determined that AMPs isolated from R. okinavana were in fact products of R.
      kobai, but not of R. ulma. In the present study, we collected skin samples from
      the species R. ulma and cloned twelve cDNAs encoding AMP precursors for the
      acyclic brevinin-1ULa--1ULf, the temporin-ULa-ULc, ranatuerin-2ULa, japonicin
      1ULa, and a novel peptide using reverse-transcription polymerase chain reaction
      techniques. The deduced amino acid sequence of the novel peptide had a high
      similarity to those of Rana chensinensis chensinin-1CEa--1CEc, which were cloned
      by Zhao et al. ( 2011 ), but had a low similarity with R. chensinensis chensinin
      1, which was cloned by Shang et al. ( 2009 ). To avoid confusion with these two
      different chensinin-1 families, we termed our peptide ulmin-1. Among these
      peptides, we focused on two peptides, brevinin-1ULf and ulmin-1ULa, and examined
      the antimicrobial and cytotoxic activity of their synthetic replicates. In broth
      microdilution assays, growth inhibitory activities against Staphylococcus aureus,
      Bacillus cereus, and Candida albicans were detected for brevinin-1ULf but not for
      ulmin-1ULa, whereas scanning electron microscopic observations revealed that both
      peptides induce morphological abnormalities in these microbes. In addition,
      binding activity of ulmin-1ULa to the bacterial cell wall component lipoteichoic
      acid was higher than that of brevinin-1ULf. In contrast, hemolytic and cytotoxic
      activities of brevinin-1ULf were stronger than those of ulmin-1ULa.

PMID- 29219047
TI  - The effects of genetic polymorphism on treatment response of recombinant human
      growth hormone.
AB  - Recombinant human growth hormone (rhGH) has been widely used in clinical
      treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology
      have achieved a great development in different long-acting formulations. Although
      the mathematical models for predicting the growth hormone response could help
      clinicians get to an individual personalized growth dose, many patients just
      can't reach the target height and the growth hormone responses differed.Genetic
      polymorphisms may play a role in the varies of individual responses in this
      treatment process.This article gives an overview of the genetic polymorphisms
      research of growth hormone in recent years, in order to give some potential
      suggestion and guide for the dose titration during treatment.

PMID- 29219048
TI  - Sodium Oxybate Therapy for Alcohol Withdrawal Syndrome and Keeping of Alcohol
      Abstinence.
AB  - BACKGROUND: Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous
      and endogenous molecule with neuromodulator properties. In the United States, GHB
      is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy
      in adults. In some European Union countries, sodium oxybate is applied for the
      treatment of opioid and alcohol withdrawal. OBJECTIVE: The aim of the present
      review was to describe the state of art of the pre-clinical research and the
      clinical evidence related to GHB used alone or in combination with other
      treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance.
      METHOD: Internationally published pre-clinical findings and clinical studies
      investigating the effects of GHB on alcohol withdrawal syndrome and alcohol
      abstinence maintenance were collected and described considering seven clinical
      studies involving GHB in the treatment of alcohol withdrawal abstinence and five
      clinical studies involving GHB in the treatment of alcohol abstinence
      maintenance. Furthermore, GHB pharmacology and characteristics of abuse were
      briefly detailed. RESULTS: Clinical evidence indicates that GHB is effective in
      reducing symptoms of alcohol withdrawal syndrome and produces beneficial effects
      comparable to those of benzodiazepines or chlometiazole. GHB proved effective in
      increasing alcohol abstinence maintenance and in reducing alcohol craving, but it
      did not show any influence in relapses of heavy drinkers when given alone.
      Conversely, it seems to be effective in reducing relapses in alcohol dependent
      patients when given in combination with naltrexone and escitalopram. CONCLUSION:
      Despite this bunch of evidence, studies are still limited and investigations
      including a larger number of patients are needed. In addition, some safety
      concerns, such as insufficiency against hallucinations in alcohol withdrawal and
      potential development of GHB dependence have to be more investigated.

PMID- 29219049
TI  - Role of Mitochondrial Mechanism in Chemotherapy-Induced Peripheral Neuropathy.
AB  - BACKGROUND: Even though chemotherapeutic regimens show considerable importance,
      it may cause progressive, continuing and sometimes irreversible peripheral
      neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) is comprised of
      sensory abnormalities that are most distressing issues. The mechanism associated
      with CIPN pathogenesis is not completely revealed and its treatment is still
      questionable. The purpose of this review was to investigate the role of
      mitochondria in CIPN. METHODS: This review is literature based that describes the
      mitochondrial mechanism underlying CIPN and the neuropathic complications
      associated with different antineoplastic agents. RESULTS: For severe pain, a
      modification towards less efficient chemotherapeutic drugs could possibly be
      needed and/or patients perhaps prefer to withdrawal therapeutic regimen. The
      epidemiology of CIPN is still debatable. The major recurrent molecules causing
      CIPN are platinum based drugs including cisplatin and oxaliplatin, thalidomide,
      bortezomib, vinka alkaloids and taxanes. Neuropathic pain is one of the symptoms
      of CIPN. Various neuropathic disorders as well as CIPN are due to mitochondrial
      impairment, relevant impairment of Ca2+ signalling pathways and reactive oxygen
      species (ROS) that ultimately leads to apoptosis. CONCLUSION: The pathophysiology
      of CIPN is complicated as chemotherapeutic medications often involve combination
      of drugs. With these combinatorial therapies cancer survivors develop continuing
      effects of CIPN which require rehabilitation strategies for the recovery of
      patient's condition and quality of life.

PMID- 29219050
TI  - Long Circulating Polymeric Nanoparticles for Gene/Drug Delivery.
AB  - BACKGROUND: The prolonged circulation time of nanoparticles in the blood is a
      prerequisite to realize a controlled and targeted (passive or active targeting)
      release of the encapsulated gene/drug at the desired site of action. The most
      popular method to mask or camouflage nanoparticles is the adsorbed, grafted or
      conjugated of poly (ethylene glycol) (PEG) or other hydrophilic polymers (e.g.
      polysaccharides) to the particle surface. However, the circulation half-life of
      nanoparticles still cannot satisfy the need of clinical use. METHOD: This review
      focuses on several recent advances in the design and fabrication of polymeric
      nanoparticles with long circulating characters in blood. The factors influencing
      the physicochemical characteristics of nanoparticle surface and its surface
      modification have been discussed. RESULTS: Gene/drug carriers can also be
      combined with functionalized physical, chemical or biological stimuli to improve
      passive and active targeting strategies. The choice of suitable manufacturing
      technique of polymeric nanoparticles depends on the gene/drug to be encapsulated
      in the particle, the physicochemical properties of the polymer, their therapeutic
      goal to be reached and the scalability of the fabrication which allows for a
      clinical realization of the most promising nanomedicines. The factors influencing
      long circulating properties of nanoparticles are mainly particle size, surface
      charge and hydrophilicity. Surface modification of polymeric nanoparticles has
      been focused on PEG, polysaccharides, and so on. CONCLUSION: Identification of
      novel potential coating materials with satisfied characters is an emerging field
      of interest in the design of long circulating polymer-based nanoparticulate
      gene/drug delivery.

PMID- 29219052
TI  - Adverse Events of Proton Pump Inhibitors: Potential Mechanisms.
AB  - OBJECTIVE: We aimed at summarizing current evidence about mechanisms for
      potentially harmful effects of Proton Pump Inhibitors (PPIs). METHODS: A Pubmed
      search was performed, and 207 studies concerning the relationship between use of
      PPIs and cardiovascular diseases, kidney impairment, nutritional disorders,
      fractures, infections, functional decline, and mortality were selected and
      reviewed. RESULTS: PPIs may cause potentially harmful effects by several
      mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions,
      reduced absorption of selected nutrients, increased gastric microbiota and small
      intestine bacterial overgrowth, reduced immune response, tubular-interstitial
      inflammation, increased bone turnover, accumulation of amyloid in the brain.
      Clinical and epidemiologic evidence is not consistent in regard to some negative
      outcomes during PPI treatment. Data from randomized clinical trials seem to deny
      most of them, but they are usually designed to investigate efficacy of drugs in
      ideal conditions and are not powered enough to detect adverse events. Besides
      being at special risk of experiencing negative outcomes during long-term
      treatment with PPIs, older and complex patients treated with polypharmacy
      regimens are persistently excluded from randomized clinical trials. Thus, large
      observational studies involving real-world patients should be considered as an
      important informative source about potential risks related to PPIs. CONCLUSIONS:
      Current evidence suggests that use of PPIs may be associated with negative
      outcomes by eliciting several different pathophysiologic mechanisms. While short
      term PPIs could be considered effective and safe in adult patients with acid
      related disorders, their long-term and often inappropriate use in patients
      carrying vulnerability to adverse events and/or high risk of drug-interactions
      should be avoided.

PMID- 29219053
TI  - Triazolopyrimidines and Thiazolopyrimidines: Synthesis, Anti-HSV-1, Cytotoxicity
      and Mechanism of Action.
AB  - BACKGROUND: Several commercial drugs utilized in the treatment of HSV containing
      pyrimidine moiety. Because of the ineffectiveness of virus drugs due to the
      resistance of the patient's immune system, there is a pressing need to prepare
      new compounds that are effective in the treatment of various viruses. RESULTS:
      Merged pyrimidine derivatives were designed by one pot synthesis of
      pyrimidinethione derivative with halogenated compounds. The structure of all
      prepared compounds was characterized by their spectroscopic data and also, their
      ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the
      tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2-
      a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6
      dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral
      inhibition over 90%. Furthermore, the selectivity indices of the tested compounds
      are high and have weak cytotoxicity (all samples were checked, not chosen on
      cytotoxicity basis, we only utilize secure concentrations of every compound).
      CONCLUSION: We succeeded in this context to synthesize a new series of potent
      fused pyrimidine derivatives as anti-HSV-1.

PMID- 29219054
TI  - Antioxidant effects of polysaccharides from traditional Chinese medicines.
AB  - Polysaccharides are a kind of biological macromolecules with immune regulation,
      anti-tumor, anti-radiation, anti-inflammation, anti-fatigue and anti-aging
      effects. These effects are related to their antioxidant properties. The action
      mechanisms of antioxidation and scavenging free radicals for polysaccharides were
      reviewed. The polysaccharides contain plant polysaccharides, animal
      polysaccharides and microbial polysaccharides. The recent research progresses and
      our work on antioxidant properties of polysaccharides and their derivatives were
      summarized. At last, the existing problems of antioxidant polysaccharides were
      analyzed, and the development prospects were also presented. It is important to
      study the antioxidant activities of polysaccharides and their derivatives for the
      development of natural antioxidants.

PMID- 29219051
TI  - Development and Uses of Offline and Web-Searchable Metabolism Databases - The
      Case of Benzo[a]pyrene.
AB  - BACKGROUND: The present work describes development of offline and web-searchable
      metabolism databases for drugs, other chemicals, and physiological compounds
      using human and model species, prompted by the large amount of data published
      after year 1990. The intent was to provide a rapid and accurate approach to
      published data to be applied both in science and to assist therapy. METHODS:
      Searches for the data were done using the Pub Med database, accessing the Medline
      database of references and abstracts. In addition, data presented at scientific
      conferences (e.g., ISSX conferences) are included covering the publishing period
      beginning with the year 1976. RESULTS: Application of the data is illustrated by
      the properties of benzo[a]pyrene (B[a]P) and its metabolites. Analysis show
      higher activity of P450 1A1 for activation of the (-)- isomer of trans-B[a]P-7,8
      diol, while P4501B1 exerts higher activity for the (+)- isomer. P450 1A2 showed
      equally low activity in the metabolic activation of both isomers. CONCLUSION: The
      information collected in the databases is applicable in prediction of metabolic
      drug-drug and/or drug-chemical interactions in clinical and environmental
      studies. The data on the metabolism of searched compound (exemplified by
      benzo[a]pyrene and its metabolites) also indicate toxicological properties of the
      products of specific reactions. The offline and web-searchable databases had wide
      range of applications (e.g. computer assisted drug design and development,
      optimization of clinical therapy, toxicological applications) and adjustment in
      everyday life styles.

PMID- 29219055
TI  - The Role of Nanoparticles in the Inhibition of Multidrug-Resistant Bacteria and
      Biofilms.
AB  - BACKGROUND: Until recently, one of the main reasons for mortality has been
      infectious diseases, and bacteria that are drug-resistant have emerged as a
      result of the wide application, as well as the misuse of antibacterial
      medications. Having multidrug-resistance, bacteria present a great problem for
      the efficient management of bacterial infections and this challenge has resulted
      in the creation of other means of dealing with bacterial diseases. Of late,
      metallic nanoparticles (NPs), employed as antibacterial agents, have the
      potential for use against resistance to bacterial drugs. OBJECTIVE: The
      mechanisms of bacterial resistance are described in this review and this is
      followed by an outline of the features and uses of metallic NPs as antibiotic
      agents to address bacteria that are antibiotic- sensitive and resistant.
      Additionally, a general impression of metallic NPs as antibiofilm bactericidal
      agents is presented. CONCLUSION: Biofilms and bacterial strains that are
      resistant to antibiotics present a grave public health challenge and this has
      enhanced the need to develop new bactericidal agents. Therefore, nanomaterials
      are considered as a potential platform for managing bacterial infections.

PMID- 29219056
TI  - In-vitro and In-vivo Pharmacokinetic Evaluation of Guar Gum-Eudragit&#174; S100
      Based Colon-targeted Spheroids of Sulfasalazine Co-administered with Probiotics.
AB  - BACKGROUND: Polysaccharide based delivery systems have been successfully used to
      target drugs to colon. In some recent reports, the superiority of concomitant
      administration of probiotics with such systems has been established. However, the
      pharmacokinetics of such symbiotic therapy remain unexplored hitherto. METHODS:
      This study deciphers the pharmacokinetic parameters of guar gum based colon
      targeted spheroids of sulfasalazine with co-administration of probiotics in
      experimental rats. Thirty rats were divided into five groups using Latin square
      design. These were subjected to treatment with delayed release formulation,
      uncoated spheroids, coated spheroid and coated spheroids along with probiotics.
      RESULTS: In case of delayed release formulation, negligible presence of
      sulfasalazine in plasma was observed in first 2h, followed by significant
      increase in sulfasalazine concentration after 3h. Higher plasma concentrations of
      sulfasalazine were detected for uncoated spheroids with and without probiotics.
      Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated
      sulfasalazine spheroids with or without probiotics clearly indicated successful
      formulation of colon targeted spheroids. Further, for coated spheroids (both with
      and without probiotics), the value of Tmax is found to be significantly higher
      than those with the other treatments. CONCLUSION: Colon targeted spheroids were
      therefore, found to reduce absorption of drug which, in turn, is expected to
      reduce the side effects as only local action in colon is required for treatment
      of colitis. This is the first report on pharmacokinetic study of a colon targeted
      delivery system co-administered with probiotics.

PMID- 29219057
TI  - Formulation Optimization and In-vitro and In-vivo Evaluation of Lornoxicam
      Ethosomal Gels with Penetration Enhancers.
AB  - BACKGROUND: Ethosomes, a novel type of percutaneous drug delivery carrier with a
      lipid bilayer structure, penetrate the skin barrier due to their deformability
      and malleability, and presence of ethanol that fluidizes lipids in the skin. In
      order to further enhance the delivery of drugs through the skin, penetration
      enhancers are widely used. OBJECTIVE: The objective of this work was to develop
      an optimized formulation of lornoxicam ethosomal gels, investigate skin
      permeability with the addition of penetration enhancers, and evaluate the invivo
      pharmacodynamics of these formulations. METHODS: Lornoxicam ethosomes were
      prepared by the ethanol injection method and optimized using the orthogonal
      design method. Lornoxicam ethosomal gels with enhancers were prepared and
      optimized using in-vitro transdermal delivery experiments. Experiments on
      lornoxicam ethosomal gels containing various enhancers such as azone, menthol,
      lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion
      cells to measure the percutaneous permeability of the different formulations.
      Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal
      gels were examined using the hot-plate and acetic acid-induced writhing tests.
      Anti-inflammatory activity was investigated using the dimethylbenzene-induced
      mouse ear swelling method. RESULTS: The results showed that compared to other
      formulations, the optimized lornoxicam ethosomal gels with 5 % menthol
      significantly increased transdermal penetration. Meanwhile, the optimized
      lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti
      inflammatory activity compared with the plain lornoxicam gels. CONCLUSION: These
      results suggest that the optimized ethosomal gel formulated in this study is a
      promising lornoxicam carrier in transdermal delivery systems to enhance anti
      nociceptive and antiinflammatory efficiency.

PMID- 29219058
TI  - Macrophage Targeted Cellular Carriers for Effective Delivery of Anti-Tubercular
      Drugs.
AB  - BACKGROUND: Newly developed vaccine VPM1002 confers paradigm swing in the
      prophylactic treatment of tuberculosis (TB). Multi-drug resistant and latent TB
      in adults as well as in underprivileged patients is instigating menace over world
      population if the host is immune-compromised. METHODS: One third of the world's
      population is infected with TB. Recently it is estimated around 9.6 million
      people around the world became sick with TB disease. There were 1.5 million TB
      related deaths worldwide. Therefore with the advent in biotechnology and Nano
      engineering, newly adapted survival molecular mechanism of Mycobacterium
      tuberculosis, new targets receptors on alveolar macrophages must be explored out
      for eradication of TB from the globe. Macrophage acts as a reservoir of
      phagocytic receptors to execute diverse physiological functions as well as to
      perform defense mechanism. RESULTS: Advances in novel carriers open new era for
      the treatment of tuberculosis which remains a very substantial global health
      encumbrance. Different binding receptors especially mannose, folate and scavenger
      receptors are attractive platform for internalization of therapeutics in alveolar
      macrophage. Nano-carriers and nano-devices designed after the acquaintance of
      receptor composition and functioning affords site specific targeting of
      biodegradable and biocompatible drug delivery systems for the treatment of
      tuberculosis offering complete cure and patient compliance. CONCLUSION: This
      chapter encompasses recent studies on nanocarriers and new treatment strategies
      for tuberculosis. In spite of the budding benefits of nano carriers, many
      limitations still remain to be overcome such as poor oral stability, instability
      in circulation, inadequate tissue distribution as well as toxicity to normal
      cells.

PMID- 29219059
TI  - Inhibition of intercellular communication between prostate cancer cells by a
      specific anti-STEAP-1 single chain antibody.
AB  - BACKGROUND: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is
      present at the intercellular junctions of the secretory epithelium of prostate
      and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a
      transporter protein or a putative channel between cancer cells while it has
      limited expression in normal human tissues. This protein has been suggested as an
      attractive target for prostate cancer immunotherapy. OBJECTIVE: This study aimed
      at the development of a specific single chain fragment variable (scFv) antibody
      against STEAP-1 epitope and testing the inhibitory effect of the selected scFv
      antibody in blocking gap junctions between tumor cells. METHODS: In the current
      study, a phage library was used and a specific scFv antibody was isolated against
      STEAP-1 epitope using panning process. RESULTS: PCR and DNA fingerprinting of the
      obtained clones demonstrated a dominant pattern of a specific clone. Binding of
      the selected scFv to the corresponding target on PC3 and LNCaP cell lines was
      tested using ELISA and flow cytometry techniques. The inhibitory effect of the
      selected scFv antibody in blocking gap junctions between the cells was tested
      using intercellular communication assay. The selected antibody reacted with the
      corresponding epitope in ELISA and bound to prostate cancer cells with an
      intensity of 44.6% (PC3 cells) and 73.4% (LNCap cells) as shown by FACS analysis.
      Intercellular communication assay indicated that dye transfer between the cells
      in PC3 and LNCaP cell lines treated with 1000 scFv/cell was significantly
      inhibited (80-90%). CONCLUSION: Our results suggested that the selected specific
      anti-STEAP1 scFv highly inhibited intercellular communication between prostate
      cancer cells and has the potential to be used as a new effective agent in
      prostate cancer immunotherapy.

PMID- 29219060
TI  - Nattokinase: an updated critical review on challenges and perspectives.
AB  - Natto, a fermented soybean food, has been consumed by oriental people for more
      than 1000 years. Nattokinase, formerly called subtilisin NAT is a well studied
      protease of microbial origin that possesses fibrinolytic (anti-clotting)
      activities. Due to its strong fibrinolytic and thrombolytic activity, Nattokinase
      is regarded as a precious dietary supplement or nutraceutical for the oral
      thrombolytic therapy. Nattokinase is witnessed to be a useful enzyme for the com
      plete removal of the vitreous and associated proliferative tissues in
      proliferative vitreo retinal disorders. This review focuses on the native and
      recombinant Nattokinase from bacteria and other sources, their production,
      purification, immobilization and nano-immobilization studies, which aid in
      ameliorating their properties to suit the targeted industrial applications.
      Recent development in these fields are presented and discussed, and prospective
      developments are suggested.

PMID- 29219061
TI  - Effect of Conjugated Linoleic Acid Supplementation on Serum Leptin Concentration:
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: There are controversies regarding the effect of conjugated linoleic
      acid (CLA) on serum leptin. OBJECTIVE: To conduct a meta-analysis of randomized
      controlled trials (RCTs) to assess the effect of CLA on serum leptin
      concentrations. METHOD: Databases such as Ovid, PubMed/Medline, SCOPUS, Google
      Scholar, and ISI databases up to January 2017 were searched. The searches
      included RCTs conducted among human adults, and studies on the effect of
      conjugated linoleic acid on serum leptin concentrations as outcome variables. The
      mean difference and standard deviation of leptin changes in the intervention and
      control groups were used as effect size measures for the meta-analysis. RESULT:
      Eleven trials with thirteen effect sizes were pooled in this meta-analysis. CLA
      supplementations could not reduce serum leptin levels significantly (-0.12
      (ng/ml); 95% CI: -1.29, 1.05; P=0.837). However, the impact of CLA
      supplementation differed by sex and BMI status. Compared with the control group,
      CLA administration reduced serum leptin levels significantly in trials conducted
      among male (- 0.86 (ng/ml); 95% CI: -1.11, -0.62; P<0.0001) or overweight
      individuals (-1.37 (ng /ml); 95% CI: -2.55, -0.20; P=0.022) and lasted for less
      than 8 weeks (-0.90 (ng/ml); 95% CI: -1.64, -0.17; P=0.0.016). CONCLUSION: CLA
      supplementation might be able to decrease circulating leptin levels in studies
      with duration of less than 8 weeks especially among male and overweight subjects.
      Additional RCTs that are well controlled for energy intakes may be necessary to
      explain the cause of short- and long-term effects of conjugated linoleic acid.
      The protocol was registered with PROSPERO (No. CRD42017059165).

PMID- 29219062
TI  - Assessment of Irisin, Adiponectin and Leptin Levels in Patients with
      Schizophrenia.
AB  - BACKGROUND: The patients with schizophrenia are at increased risk for problems
      regarding metabolic parameters due to their lifestyle and antipsychotic
      treatment. OBJECTIVE: In this study, we aimed to evaluate the levels of
      adiponectin, leptin, irisin in patients with schizophrenia who were nondiabetic,
      nonobese and under antipsychotic treatment. METHOD: 5 ml sample of venous blood
      was collected from each participant. Blood cells were separated from the serum.
      The serum samples were stored in a -80 degrees C freezer. Biochemical analyses
      were performed on these samples. Adiponectin, leptin and irisin levels were
      measured by Enzyme Linked Immunosorbent Assay method. RESULTS: The study included
      88 subjects. Of them, 44 were patients with schizophrenia and 44 were healthy
      controls. There were no statistically significant results when the c-reactive
      protein, adiponectin, leptin and irisin levels were compared between the
      schizophrenia and the control group (p>0.05). CONCLUSION: In our study,
      adiponectin, leptin and irisin levels in patients with schizophrenia did not
      present a statistically significant difference from healthy controls. Therefore,
      there is a need for studies including more participants to investigate the level
      of irisin in patients with schizophrenia.

PMID- 29219063
TI  - An Insight on the Pathogenesis and Treatment of Systemic Lupus Erythematosus.
AB  - BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is a diverse
      autoimmune disorder, evoked in response to self-immune system that leads to
      immune complex depositions and organ damage. The exact mechanism of SLE
      pathogenesis is still unclear but certain genetic and environmental factors have
      been suggested that could influence its pathogenesis. DISCUSSION: The modulation
      in B- and T- cell responses and genetic variations could lead to abnormal
      lymphocyte functions and the production of antibodies against the indigenous
      proteins and the immune complex depositions. CONCLUSION: The present review
      highlights the various causatives of SLE, particularly the genetic alteration in
      B- and T-cell-related proteins. We have also delineated some of the available
      therapeutic strategies for the treatment of SLE.

PMID- 29219064
TI  - Natural Product Formulations for the Prevention and Treatment of Alzheimer's
      disease: A Patent Review.
AB  - INTRODUCTION: Although considerable efforts have been made to develop effective
      therapeutic agents for Alzheimer's Disease (AD), neither a consensus concerning
      the pathogenesis of the disease nor a successful therapy for its treatment is yet
      available. The natural product chemistry brings tremendous diversity and abundant
      resource for medical needs. OBJECTIVES: The present review summarizes recent
      patents on natural extracts and derived drugs as agents for the prevention and
      treatment of AD. It also sums up the suggested mechanisms of action of the
      formulated natural remedies. CONCLUSION: It is now becoming well accepted that
      multiple factors contribute to the progression of AD. The pathogenesis of the
      disease involves amyloid-beta cascade, tau hyperphosphorylation, oxidative
      stress, inflammation, mitochondrial dysfunction, protein misfolding, gene
      mutation, etc. It has been suggested that the multifactorial nature of AD
      pathogenesis requires the design of medicines with a wide spectrum of activity.
      Medicinal herbs are known to consist of multiple compounds and may implicate
      multiple mechanisms, thus being advantageous over the simple single-target drugs
      in the treatment of complex diseases. Indeed, natural products attract increased
      attention. In the last decades, they have become a major focus in the quest for
      AD remedies and may represent a real promise for curing the disease.

PMID- 29219065
TI  - Transactivation Assays that Identify Indirect and Direct Activators of Human
      Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR,
      NR1I3).
AB  - BACKGROUND: Nuclear Receptors (NRs), including PXR and CAR, are presumed to be
      ligand-dependent transcription factors, but ligand binding is not an absolute
      requirement for activation. Indeed, many compounds activate PXR and CAR by
      indirect mechanisms. Detecting these indirect activators of specific nuclear
      receptors in vitro has been difficult. As NR activation of either or both PXR and
      CAR can lead to drug-drug interactions and adverse drug effects, false negatives
      obtained with screening tools incapable of detecting indirect activators could
      present liabilities. OBJECTIVE: The aim of this study was to establish assays
      that identify indirect activators of human PXR and CAR. METHODS: Commercially
      available human PXR and CAR transactivation assays were used for analyses.
      RESULTS: We show that transactivation assays containing full-length nuclear
      receptors with native promoters can identify indirect activators of human CAR and
      PXRwhen compared to those of commercially available assays containing only the
      LBD of PXR and CAR. Of these two assay systems, only human PXR and CAR1 assays
      with full-length receptors and native promoters are capable of detecting indirect
      and ligand activators. With this capability, several kinase inhibitors were
      identified that activate PXR and CAR by indirect mechanisms. Furthermore by using
      both the LBD and full-length receptors, phenobarbital and midostaurin were found
      to be direct and indirect activators of PXR while human CAR activation by
      phenobarbital occurs by indirect mechanisms only. CONCLUSION: Cell based
      transactivation assays employing the full-length receptors and native promoters
      identify both direct and indirect activators of either or both human PXR and CAR.

PMID- 29219066
TI  - A multi-network clustering method for detecting protein complexes from multiple
      heterogeneous networks.
AB  - BACKGROUND: The accurate identification of protein complexes is important for the
      understanding of cellular organization. Up to now, computational methods for
      protein complex detection are mostly focus on mining clusters from protein
      protein interaction (PPI) networks. However, PPI data collected by high
      throughput experimental techniques are known to be quite noisy. It is hard to
      achieve reliable prediction results by simply applying computational methods on
      PPI data. Behind protein interactions, there are protein domains that interact
      with each other. Therefore, based on domain-protein associations, the joint
      analysis of PPIs and domain-domain interactions (DDI) has the potential to obtain
      better performance in protein complex detection. As traditional computational
      methods are designed to detect protein complexes from a single PPI network, it is
      necessary to design a new algorithm that could effectively utilize the
      information inherent in multiple heterogeneous networks. RESULTS: In this paper,
      we introduce a novel multi-network clustering algorithm to detect protein
      complexes from multiple heterogeneous networks. Unlike existing protein complex
      identification algorithms that focus on the analysis of a single PPI network, our
      model can jointly exploit the information inherent in PPI and DDI data to achieve
      more reliable prediction results. Extensive experiment results on real-world data
      sets demonstrate that our method can predict protein complexes more accurately
      than other state-of-the-art protein complex identification algorithms.
      CONCLUSIONS: In this work, we demonstrate that the joint analysis of PPI network
      and DDI network can help to improve the accuracy of protein complex detection.

PMID- 29219067
TI  - Prediction of essential proteins based on subcellular localization and gene
      expression correlation.
AB  - BACKGROUND: Essential proteins are indispensable to the survival and development
      process of living organisms. To understand the functional mechanisms of essential
      proteins, which can be applied to the analysis of disease and design of drugs, it
      is important to identify essential proteins from a set of proteins first. As
      traditional experimental methods designed to test out essential proteins are
      usually expensive and laborious, computational methods, which utilize biological
      and topological features of proteins, have attracted more attention in recent
      years. Protein-protein interaction networks, together with other biological data,
      have been explored to improve the performance of essential protein prediction.
      RESULTS: The proposed method SCP is evaluated on Saccharomyces cerevisiae
      datasets and compared with five other methods. The results show that our method
      SCP outperforms the other five methods in terms of accuracy of essential protein
      prediction. CONCLUSIONS: In this paper, we propose a novel algorithm named SCP,
      which combines the ranking by a modified PageRank algorithm based on subcellular
      compartments information, with the ranking by Pearson correlation coefficient
      (PCC) calculated from gene expression data. Experiments show that subcellular
      localization information is promising in boosting essential protein prediction.

PMID- 29219068
TI  - Predicting enhancers with deep convolutional neural networks.
AB  - BACKGROUND: With the rapid development of deep sequencing techniques in the
      recent years, enhancers have been systematically identified in such projects as
      FANTOM and ENCODE, forming genome-wide landscapes in a series of human cell
      lines. Nevertheless, experimental approaches are still costly and time consuming
      for large scale identification of enhancers across a variety of tissues under
      different disease status, making computational identification of enhancers
      indispensable. RESULTS: To facilitate the identification of enhancers, we propose
      a computational framework, named DeepEnhancer, to distinguish enhancers from
      background genomic sequences. Our method purely relies on DNA sequences to
      predict enhancers in an end-to-end manner by using a deep convolutional neural
      network (CNN). We train our deep learning model on permissive enhancers and then
      adopt a transfer learning strategy to fine-tune the model on enhancers specific
      to a cell line. Results demonstrate the effectiveness and efficiency of our
      method in the classification of enhancers against random sequences, exhibiting
      advantages of deep learning over traditional sequence-based classifiers. We then
      construct a variety of neural networks with different architectures and show the
      usefulness of such techniques as max-pooling and batch normalization in our
      method. To gain the interpretability of our approach, we further visualize
      convolutional kernels as sequence logos and successfully identify similar motifs
      in the JASPAR database. CONCLUSIONS: DeepEnhancer enables the identification of
      novel enhancers using only DNA sequences via a highly accurate deep learning
      model. The proposed computational framework can also be applied to similar
      problems, thereby prompting the use of machine learning methods in life sciences.

PMID- 29219069
TI  - A boosting approach for prediction of protein-RNA binding residues.
AB  - BACKGROUND: RNA binding proteins play important roles in post-transcriptional RNA
      processing and transcriptional regulation. Distinguishing the RNA-binding
      residues in proteins is crucial for understanding how protein and RNA recognize
      each other and function together as a complex. RESULTS: We propose PredRBR, an
      effectively computational approach to predict RNA-binding residues. PredRBR is
      built with gradient tree boosting and an optimal feature set selected from a
      large number of sequence and structure characteristics and two categories of
      structural neighborhood properties. In cross-validation experiments on the RBP170
      data set show that PredRBR achieves an overall accuracy of 0.84, a sensitivity of
      0.85, MCC of 0.55 and AUC of 0.92, which are significantly better than that of
      other widely used machine learning algorithms such as Support Vector Machine,
      Random Forest, and Adaboost. We further calculate the feature importance of
      different feature categories and find that structural neighborhood
      characteristics are critical in the recognization of RNA binding residues. Also,
      PredRBR yields significantly better prediction accuracy on an independent test
      set (RBP101) in comparison with other state-of-the-art methods. CONCLUSIONS: The
      superior performance over existing RNA-binding residue prediction methods
      indicates the importance of the gradient tree boosting algorithm combined with
      the optimal selected features.

PMID- 29219070
TI  - Predicting human splicing branchpoints by combining sequence-derived features and
      multi-label learning methods.
AB  - BACKGROUND: Alternative splicing is the critical process in a single gene coding,
      which removes introns and joins exons, and splicing branchpoints are indicators
      for the alternative splicing. Wet experiments have identified a great number of
      human splicing branchpoints, but many branchpoints are still unknown. In order to
      guide wet experiments, we develop computational methods to predict human splicing
      branchpoints. RESULTS: Considering the fact that an intron may have multiple
      branchpoints, we transform the branchpoint prediction as the multi-label learning
      problem, and attempt to predict branchpoint sites from intron sequences. First,
      we investigate a variety of intron sequence-derived features, such as sparse
      profile, dinucleotide profile, position weight matrix profile, Markov motif
      profile and polypyrimidine tract profile. Second, we consider several multi-label
      learning methods: partial least squares regression, canonical correlation
      analysis and regularized canonical correlation analysis, and use them as the
      basic classification engines. Third, we propose two ensemble learning schemes
      which integrate different features and different classifiers to build ensemble
      learning systems for the branchpoint prediction. One is the genetic algorithm
      based weighted average ensemble method; the other is the logistic regression
      based ensemble method. CONCLUSIONS: In the computational experiments, two
      ensemble learning methods outperform benchmark branchpoint prediction methods,
      and can produce high-accuracy results on the benchmark dataset.

PMID- 29219071
TI  - Systematic review of the relationships between combinations of movement
      behaviours and health indicators in the early years (0-4 years).
AB  - BACKGROUND: A recent review highlighted important relationships between
      combinations of movement behaviours (i.e., sleep, sedentary behaviour, and
      physical activity) and health indicators among school-aged children and youth
      (aged 5-17 years). It is unclear whether similar relationships exist in younger
      children. Therefore, this review sought to examine the relationships between
      combinations of movement behaviours and health indicators in the early years
      (1.00 month to 4.99 years). METHODS: Medline, EMBASE, PsycINFO, and SportDiscus
      were searched for relevant studies up to November 2016, with no date or study
      design limits. Included studies met the a priori-determined population
      (apparently healthy children aged 1.00 month to 4.99 years), intervention
      (combination of >=2 movement behaviours [i.e., sleep and sedentary behaviour;
      sleep and physical activity; sedentary behaviour and physical activity; and
      sleep, sedentary behaviour, and physical activity]), comparator (various levels
      and combinations of movement behaviours), and health outcome/indicator (Critical:
      adiposity, motor development, psychosocial health/emotional regulation, cognitive
      development, fitness, and growth; Important: bone and skeletal health,
      cardiometabolic health, and risks). For each health indicator, quality of
      evidence was assessed by study design using the Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) framework. RESULTS: Ten articles
      (n = 7436 participants; n = 5 countries) were included. Across observational and
      experimental study designs, the most ideal combinations of sedentary behaviour
      and physical activity were: favourably associated with motor development and
      fitness among preschool-aged children (3.00 to 4.99 years); both favourably and
      not associated with adiposity among toddlers (1.10 to 2.99 years) and preschool
      aged children; and not associated with growth among toddlers and preschool-aged
      children. The most ideal combinations of sleep and sedentary behaviour were
      favourably associated with adiposity among infants (1.00 month to 1.00 years) and
      toddlers. Quality of evidence ranged from "very low" to "moderate". CONCLUSIONS:
      The most ideal combinations of movement behaviours (e.g., high sleep, low
      sedentary behaviour, high physical activity) may be important for optimal health
      in the early years. Findings can help inform movement behaviour guidelines for
      the early years. Given the limited evidence, future research is needed to
      determine the ideal distribution of daily movement behaviours for optimal health
      throughout the early years.

PMID- 29219072
TI  - A deep auto-encoder model for gene expression prediction.
AB  - BACKGROUND: Gene expression is a key intermediate level that genotypes lead to a
      particular trait. Gene expression is affected by various factors including
      genotypes of genetic variants. With an aim of delineating the genetic impact on
      gene expression, we build a deep auto-encoder model to assess how good genetic
      variants will contribute to gene expression changes. This new deep learning model
      is a regression-based predictive model based on the MultiLayer Perceptron and
      Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked
      denoising auto-encoder for feature selection and a multilayer perceptron
      framework for backpropagation. We further improve the model by introducing
      dropout to prevent overfitting and improve performance. RESULTS: To demonstrate
      the usage of this model, we apply MLP-SAE to a real genomic datasets with
      genotypes and gene expression profiles measured in yeast. Our results show that
      the MLP-SAE model with dropout outperforms other models including Lasso, Random
      Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with
      dropout, we show that gene expression quantifications predicted by the model
      solely based on genotypes, align well with true gene expression patterns.
      CONCLUSION: We provide a deep auto-encoder model for predicting gene expression
      from SNP genotypes. This study demonstrates that deep learning is appropriate for
      tackling another genomic problem, i.e., building predictive models to understand
      genotypes' contribution to gene expression. With the emerging availability of
      richer genomic data, we anticipate that deep learning models play a bigger role
      in modeling and interpreting genomics.

PMID- 29219073
TI  - Proportion of infants meeting the Australian 24-hour Movement Guidelines for the
      Early Years: data from the Melbourne InFANT Program.
AB  - BACKGROUND: Little information is available on the movement behaviours of
      infants, despite evidence that these are important for development. The release
      of new Australian 24-hour Movement Guidelines provides an opportunity to document
      the current state of movement behaviours in infants relative to these guidelines.
      The aim of this study was to report the prevalence of 4 month old Australian
      infants meeting the 24-hour Movement Guidelines, individually, and in
      combination, and to describe associations with individual characteristics.
      METHODS: Maternal report baseline data from the Melbourne Infant Feeding,
      Activity and Nutrition Trial Program were used to determine prevalence of infants
      meeting physical activity (30 min of tummy time per day), sedentary behaviour (no
      more than 1 h at a time kept restrained; zero screen time), and sleep guidelines
      (14-17 h for 0-3 month olds or 12-16 h for 4-11 month olds). Prevalence of
      infants meeting combined guidelines was also described. The odds of meeting
      guidelines based on infant and family characteristics was determined. RESULTS:
      Data are reported for 455 infants with a mean age of 3.6 months (SD = 1.0). The
      proportion of infants meeting each of the guidelines was 29.7% for tummy time,
      56.9% for kept restrained, 27.9% for screen time, 58.7% for sleep and 3.5% for
      the combined guidelines (i.e. meeting all four guidelines). A significantly
      higher proportion of girls than boys met the screen time guideline (32.5% versus
      24.0%, p = 0.04) and the combined guidelines (5.7% versus 1.6%, p = 0.01). Few
      associations were observed between infant and family characteristics and
      proportion of infants meeting individual guidelines. CONCLUSIONS: Very few
      infants met all of the guidelines contained in the new Australian 24-hour
      Movement Guidelines suggesting there is much room for improvement in movement
      behaviours from early life. Fewer infants met the tummy time and screen time
      guidelines hence these appear to be the behaviours requiring most attention.
      Parents and others providing care to infants require support and strategies to
      assist them in adhering to the guidelines to ensure optimal health and
      development for the youngest in our population.

PMID- 29219074
TI  - Economic cost and quality of life of family caregivers of schizophrenic patients
      attending psychiatric hospitals in Ghana.
AB  - BACKGROUND: Low and middle income countries face many challenges in meeting their
      populations' mental health care needs. Though family caregiving is crucial to the
      management of severe mental health disabilities, such as schizophrenia, the
      economic costs borne by family caregivers often go unnoticed. In this study, we
      estimated the household economic costs of schizophrenia and quality of life of
      family caregivers in Ghana. METHODS: We used a cost of illness analysis approach.
      Quality of life (QoL) was assessed using the abridged WHO Quality of Life (WHOQOL
      BREF) tool. Cross-sectional data were collected from 442 caregivers of patients
      diagnosed with schizophrenia at least six months prior to the study and who
      received consultation in any of the three psychiatric hospitals in Ghana.
      Economic costs were categorized as direct costs (including medical and non
      medical costs of seeking care), indirect costs (productivity losses to
      caregivers) and intangible costs (non-monetary costs such as stigma and pain).
      Direct costs included costs of medical supplies, consultations, and travel.
      Indirect costs were estimated as value of productive time lost (in hours) to
      primary caregivers. Intangible costs were assessed using the Zarit Burden
      Interview (ZBI). We employed multiple regression models to assess the covariates
      of costs, caregiver burden, and QoL. RESULTS: Total monthly cost to caregivers
      was US$ 273.28, on average. Key drivers of direct costs were medications (50%)
      and transportation (27%). Direct costs per caregiver represented 31% of the
      reported monthly earnings. Mean caregiver burden (measured by the ZBI) was 16.95
      on a scale of 0-48, with 49% of caregivers reporting high burden. Mean QoL of
      caregivers was 28.2 (range: 19.6-34.8) out of 100. Better educated caregivers
      reported lower indirect costs and better QoL. Caregivers with higher severity of
      depression, anxiety and stress reported higher caregiver burden and lower QoL.
      Males reported better QoL. CONCLUSIONS: These findings highlight the high
      household burden of caregiving for people living with schizophrenia in low income
      settings. Results underscore the need for policies and programs to support
      caregivers.

PMID- 29219075
TI  - Proportion of preschool-aged children meeting the Canadian 24-Hour Movement
      Guidelines and associations with adiposity: results from the Canadian Health
      Measures Survey.
AB  - BACKGROUND: New Canadian 24-Hour Movement Guidelines for the Early Years have
      been released in 2017. According to the guidelines, within a 24-h period,
      preschoolers should accumulate at least 180 min of physical activity (of which at
      least 60 min is moderate-to-vigorous physical activity), engage in no more than 1
      h of screen time, and obtain between 10 and 13 h of sleep. This study examined
      the proportions of preschool-aged (3 to 4 years) Canadian children who met these
      new guidelines and different recommendations within the guidelines, and the
      associations with adiposity indicators. METHODS: Participants were 803 children
      (mean age: 3.5 years) from cycles 2-4 of the Canadian Health Measures Survey
      (CHMS), a nationally representative cross-sectional sample of Canadians. Physical
      activity was accelerometer-derived, and screen time and sleep duration were
      parent-reported. Participants were classified as meeting the overall 24-Hour
      Movement Guidelines if they met all three specific time recommendations for
      physical activity, screen time, and sleep. The adiposity indicators in this study
      were body mass index (BMI) z-scores and BMI status (World Health Organization
      Growth Standards). RESULTS: A total of 12.7% of preschool-aged children met the
      overall 24-Hour Movement Guidelines, and 3.3% met none of the three
      recommendations. A high proportion of children met the sleep duration (83.9%) and
      physical activity (61.8%) recommendations, while 24.4% met the screen time
      recommendation. No associations were found between meeting individual or combined
      recommendations and adiposity. CONCLUSIONS: Very few preschool-aged children in
      Canada (~13%) met all three recommendations contained within the 24-Hour Movement
      Guidelines. None of the combinations of recommendations were associated with
      adiposity in this sample. Future work should focus on identifying innovative ways
      to reduce screen time in this population, and should examine the associations of
      guideline adherence with health indicators other than adiposity.

PMID- 29219076
TI  - "It takes more than a fellowship program": reflections on capacity strengthening
      for health systems research in sub-Saharan Africa.
AB  - Sub-Saharan Africa (SSA) experiences an acute dearth of well-trained and skilled
      researchers. This dearth constrains the region's capacity to identify and address
      the root causes of its poor social, health, development, and other outcomes.
      Building sustainable research capacity in SSA requires, among other things,
      locally led and run initiatives that draw on existing regional capacities as well
      as mutually beneficial global collaborations. This paper describes a regional
      research capacity strengthening initiative-the African Doctoral Dissertation
      Research Fellowship (ADDRF) program. This Africa-based and African-led initiative
      has emerged as a practical and tested platform for producing and nurturing
      research leaders, strengthening university-wide systems for quality research
      training and productivity, and building a critical mass of highly-trained African
      scholars and researchers. The program deploys different interventions to ensure
      the success of fellows. These interventions include research methods and
      scientific writing workshops, research and reentry support grants, post-doctoral
      research support and placements, as well as grants for networking and scholarly
      conferences attendance. Across the region, ADDRF graduates are emerging as
      research leaders, showing signs of becoming the next generation of world-class
      researchers, and supporting the transformations of their home-institutions. While
      the contributions of the ADDRF program to research capacity strengthening in the
      region are significant, the sustainability of the initiative and other research
      and training fellowship programs on the continent requires significant
      investments from local sources and, especially, governments and the private
      sector in Africa. The ADDRF experience demonstrates that research capacity
      building in Africa is possible through innovative, multifaceted interventions
      that support graduate students to develop different critical capacities and
      transferable skills and build, expand, and maintain networks that can sustain
      them as scholars and researchers.

PMID- 29219077
TI  - Cross-sectional associations between sleep duration, sedentary time, physical
      activity, and adiposity indicators among Canadian preschool-aged children using
      compositional analyses.
AB  - BACKGROUND: Sleep duration, sedentary behaviour, and physical activity are three
      co-dependent behaviours that fall on the movement/non-movement intensity
      continuum. Compositional data analyses provide an appropriate method for
      analyzing the association between co-dependent movement behaviour data and health
      indicators. The objectives of this study were to examine: (1) the combined
      associations of the composition of time spent in sleep, sedentary behaviour,
      light-intensity physical activity (LPA), and moderate- to vigorous-intensity
      physical activity (MVPA) with adiposity indicators; and (2) the association of
      the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity
      indicators relative to the time spent in the other behaviours in a representative
      sample of Canadian preschool-aged children. METHODS: Participants were 552
      children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures
      Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers
      (Philips Respironics, Bend, OR USA), and sleep duration was parental reported.
      Adiposity indicators included waist circumference (WC) and body mass index (BMI)
      z-scores based on World Health Organization growth standards. Compositional data
      analyses were used to examine the cross-sectional associations. RESULTS: The
      composition of movement behaviours was significantly associated with BMI z-scores
      (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z
      score: gamma sleep  = -0.72; p = 0.138; WC: gamma sleep  = -1.95; p = 0.285),
      sedentary behaviour (BMI z-score: gamma SB  = 0.19; p = 0.624; WC: gamma SB  =
      0.87; p = 0.614), LPA (BMI z-score: gamma LPA  = 0.62; p = 0.213, WC: gamma LPA 
      = 0.23; p = 0.902), or MVPA (BMI z-score: gamma MVPA  = -0.09; p = 0.733, WC:
      gamma MVPA  = 0.08; p = 0.288) relative to the other behaviours was not
      significantly associated with the adiposity indicators. CONCLUSIONS: This study
      is the first to use compositional analyses when examining associations of co
      dependent sleep duration, sedentary time, and physical activity behaviours with
      adiposity indicators in preschool-aged children. The overall composition of
      movement behaviours appears important for healthy BMI z-scores in preschool-aged
      children. Future research is needed to determine the optimal movement behaviour
      composition that should be promoted in this age group.

PMID- 29219079
TI  - Computational identification of harmful mutation regions to the activity of
      transposable elements.
AB  - BACKGROUND: Transposable elements (TEs) are interspersed DNA sequences that can
      move or copy to new positions within a genome. TEs are believed to promote
      speciation and their activities play a significant role in human disease. In the
      human genome, the 22 AluY and 6 AluS TE subfamilies have been the most recently
      active, and their transposition has been implicated in many inherited human
      diseases and in various forms of cancer. Therefore, understanding their
      transposition activity is very important and identifying the factors that affect
      their transpositional activity is of great interest. Recently, there has been
      some work done to quantify the activity levels of active Alu TEs based on
      variation in the sequence. Given this activity data, an analysis of TE activity
      based on the position of mutations is conducted. RESULTS: A method/simulation is
      created to computationally predict so-called harmful mutation regions in the
      consensus sequence of a TE; that is, mutations that occur in these regions
      decrease the transpositional activity dramatically. The methods are applied to
      the most active subfamily, AluY, to identify the harmful regions, and seven
      harmful regions are identified within the AluY consensus with q-values less than
      0.05. A supplementary simulation also shows that the identified harmful regions
      covering the AluYa5 RNA functional regions are not occurring by chance. This
      method is then applied to two additional TE families: the Alu family and the L1
      family, to computationally detect the harmful regions in these elements.
      CONCLUSIONS: We use a computational method to identify a set of harmful mutation
      regions. Mutations within the identified harmful regions decrease the
      transpositional activity of active elements. The correlation between the
      mutations within these regions and the transpositional activity of TEs are shown
      to be statistically significant. Verifications are presented using the activity
      of AluY elements and the secondary structure of the AluYa5 RNA, providing
      evidence that the method is successfully identifying harmful mutation regions.

PMID- 29219078
TI  - Systematic review of the relationships between sleep duration and health
      indicators in the early years (0-4 years).
AB  - BACKGROUND: The objective of this systematic review was to examine for the first
      time the associations between sleep duration and a broad range of health
      indicators in children aged 0 to 4 years. METHODS: Electronic databases were
      searched with no limits on date or study design. Included studies (published in
      English or French) were peer-reviewed and met the a priori determined population
      (apparently healthy children aged 1 month to 4.99 years),
      intervention/exposure/comparator (various sleep durations), and outcome criteria
      (adiposity, emotional regulation, cognitive development, motor development,
      growth, cardiometabolic health, sedentary behaviour, physical activity, quality
      of life/well-being, and risks/injuries). The quality of evidence was assessed
      using the Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) framework. Due to high levels of heterogeneity across studies, narrative
      syntheses were employed. RESULTS: A total of 69 articles/studies (62 unique
      samples) met inclusion criteria. Data across studies included 148,524 unique
      participants from 23 countries. The study designs were randomized trials (n = 3),
      non-randomized interventions (n = 1), longitudinal studies (n = 16), cross
      sectional studies (n = 42), or longitudinal studies that also reported cross
      sectional analyses (n = 7). Sleep duration was assessed by parental report in 70%
      of studies (n = 48) and was measured objectively (or both objectively and
      subjectively) in 30% of studies (n = 21). Overall, shorter sleep duration was
      associated with higher adiposity (20/31 studies), poorer emotional regulation
      (13/25 studies), impaired growth (2/2 studies), more screen time (5/5 studies),
      and higher risk of injuries (2/3 studies). The evidence related to cognitive
      development, motor development, physical activity, and quality of life/well-being
      was less clear, with no indicator showing consistent associations. No studies
      examined the association between sleep duration and cardiometabolic biomarkers in
      children aged 0 to 4 years. The quality of evidence ranged from "very low" to
      "high" across study designs and health indicators. CONCLUSIONS: Despite important
      limitations in the available evidence, longer sleep duration was generally
      associated with better body composition, emotional regulation, and growth in
      children aged 0 to 4 years. Shorter sleep duration was also associated with
      longer screen time use and more injuries. Better-quality studies with stronger
      research designs that can provide information on dose-response relationships are
      needed to inform contemporary sleep duration recommendations.

PMID- 29219080
TI  - Health practitioners' emotional reactions to caring for hospitalized children in
      Lome, Togo: a qualitative study.
AB  - BACKGROUND: Health practitioners frequently encounter dying, death and suffering.
      While providing health care can be stressful, the literature on how different
      health practitioners cope with the emotional challenges associated with their
      work is sparse. Further, much of this literature is based on studies conducted in
      high-income countries. In this study, we explored emotional distress and
      associated coping strategies among health practitioners working in a pediatric
      oncology department in a large teaching hospital in Lome, Togo. METHODS: We
      undertook a cross-sectional qualitative research involving in-depth interviews
      with 21 health practitioners (doctors, nurses, and nursing assistants) as well as
      facility-based observations Interview data were collected using a semi-structured
      discussion guide. All interviews were audio-recorded while observational notes
      were hand-written and ultimately typed. All data were transcribed, coded and
      analyzed thematically. RESULTS: We found that practitioners experienced
      significant emotional distress. Their emotional distress was compounded by the
      seriousness of the illnesses they treated, the lack of appropriate medical
      equipment, and treatment failures that caused their patients to suffer. The
      health practitioners' narratives suggested that a key reason for their emotional
      distress was a mismatch between their professional training and the realities of
      providing care in a resource-constrained setting. They also reported not
      receiving any training on how to cope with the emotional stresses associated with
      care and preventable patient deaths. CONCLUSION: Caring for patients is a source
      of significant emotional distress. The emotional stress experienced by health
      practitioners is compounded in resource-limited settings where weak health
      systems undermine practitioners' ability to provide quality care. Results
      underscore the need to train health professionals to positively cope with the
      emotional stresses associated with patient care and for health systems
      improvements to ensure quality care.

PMID- 29219081
TI  - Whole genome analysis of CRISPR Cas9 sgRNA off-target homologies via an efficient
      computational algorithm.
AB  - BACKGROUND: The beauty and power of the genome editing mechanism, CRISPR Cas9
      endonuclease system, lies in the fact that it is RNA-programmable such that Cas9
      can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA
      (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted
      mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also
      guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA.
      RESULTS: Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an
      example, this article mathematically analyzed the probabilities of off-target
      homologies of sgRNAs and discovered that for large genome size such as human
      genome, potential off-target homologies are inevitable for sgRNA selection. A
      highly efficient computationl algorithm was developed for whole genome sgRNA
      design and off-target homology searches. By means of a dynamically constructed
      sequence-indexed database and a simplified sequence alignment method, this
      algorithm achieves very high efficiency while guaranteeing the identification of
      all existing potential off-target homologies. Via this algorithm, 1,876,775
      sgRNAs were designed for the 19,153 human mRNA genes and only two sgRNAs were
      found to be free of off-target homology. CONCLUSIONS: By means of the novel and
      efficient sgRNA homology search algorithm introduced in this article, genome wide
      sgRNA design and off-target analysis were conducted and the results confirmed the
      mathematical analysis that for a sgRNA sequence, it is almost impossible to
      escape potential off-target homologies. Future innovations on the CRISPR Cas9
      gene editing technology need to focus on how to eliminate the Cas9 off-target
      activity.

PMID- 29219082
TI  - Task shifting in the management of hypertension in Kinshasa, Democratic Republic
      of Congo: a cross-sectional study.
AB  - BACKGROUND: The Democratic Republic of the Congo (DRC) is characterized by a high
      prevalence of hypertension (HTN) and a high proportion of uncontrolled HTN, which
      is indicative of poor HTN management. Effective management of HTN in the African
      region is challenging due to limited resources, particularly human resources for
      health. To address the shortage of health workers, the World Health Organization
      (WHO) recommends task shifting for better disease management and treatment.
      Although task shifting from doctors to nurses is being implemented in the DRC,
      there are no studies, to the best of our knowledge, that document the association
      between task shifting and HTN control. The aim of this study was to investigate
      the association between task shifting and HTN control in Kinshasa, DRC. METHODS:
      We conducted a cross-sectional study in Kinshasa from December 2015 to January
      2016 in five general referral hospitals (GRHs) and nine health centers (HCs). A
      total of 260 hypertensive patients participated in the study. Sociodemographic,
      clinical, health care costs and perceived health care quality assessment data
      were collected using a structured questionnaire. To examine the association
      between task shifting and HTN control, we assessed differences between GRH and HC
      patients using bivariate and multivariate analyses. RESULTS: Almost half the
      patients were female (53.1%), patients' mean age was 59.5 +/- 11.4 years. Over
      three-fourths of patients had uncontrolled HTN. There was no significant
      difference in the proportion of GRH and HC patients with uncontrolled HTN (76.2%
      vs 77.7%, p = 0.771). Uncontrolled HTN was associated with co-morbidity (OR =
      10.3; 95% CI: 3.8-28.3) and the type of antihypertensive drug used (OR = 4.6; 95%
      CI: 1.3-16.1). The mean healthcare costs in the GRHs were significantly higher
      than costs in the HCs (US$ 34.2 +/- US$3.34 versus US$ 7.7 +/- US$ 0.6,
      respectively). CONCLUSION: Uncontrolled HTN was not associated with the type of
      health facility. This finding suggests that the management of HTN at primary
      healthcare level might be just as effective as at secondary level. However, the
      high proportion of patients with uncontrolled HTN underscores the need for HTN
      management guidelines at all healthcare levels.

PMID- 29219083
TI  - A descriptive study of treatment provision for problem alcohol drinking in adult
      males in Khayelitsha, Cape Town, South Africa.
AB  - BACKGROUND: Poor, Black African males are underrepresented as patients in
      facilities that treat problem drinking in Cape Town, South Africa. Reasons for
      this remain unclear, but factors such as the kinds of treatment provided,
      perceptions of treatment efficacy, social stigma and traditional treatment
      beliefs have been suggested as possible barriers to treatment seeking. This
      descriptive study examined the availability and nature of problem drinking
      treatment facilities in Khayelitsha, a largely poor township of Black, Xhosa
      speaking Africans, on the outskirts of Cape Town. METHODS: Seven treatment
      facilities for problem drinking in adult males were identified using data from
      the Department of Social Development in the City of Cape Town. Staff members were
      identified as key informants at each of the treatment facilities, and were
      interviewed using a structured questionnaire. Twelve interviews were conducted.
      RESULTS: Findings indicated that the available alcohol treatment facilities were
      relatively new, that treatment modalities varied both across and within treatment
      facilities, and that treatment was provided largely by social workers. Treatment
      facilities did not accommodate overnight stay for patients, operated during
      weekday office hours, and commonly referred patients to the same psychiatric
      hospital. DISCUSSION: The study provides a baseline for assessing barriers to
      treatment for problem drinking in Khayelitsha by highlighting the nature of
      available facilities as playing a predominantly screening role with associated
      social work services, and a point of referral for admission to a psychiatric
      institution for treatment. The social and financial implications of such referral
      are pertinent to the discussion of treatment barriers. CONCLUSIONS:
      Recommendations are made to inform policy towards locally-provided integrated
      care to improve treatment provision and access.

PMID- 29219084
TI  - An improved Bayesian network method for reconstructing gene regulatory network
      based on candidate auto selection.
AB  - BACKGROUND: The reconstruction of gene regulatory network (GRN) from gene
      expression data can discover regulatory relationships among genes and gain deep
      insights into the complicated regulation mechanism of life. However, it is still
      a great challenge in systems biology and bioinformatics. During the past years,
      numerous computational approaches have been developed for this goal, and Bayesian
      network (BN) methods draw most of attention among these methods because of its
      inherent probability characteristics. However, Bayesian network methods are time
      consuming and cannot handle large-scale networks due to their high computational
      complexity, while the mutual information-based methods are highly effective but
      directionless and have a high false-positive rate. RESULTS: To solve these
      problems, we propose a Candidate Auto Selection algorithm (CAS) based on mutual
      information and breakpoint detection to restrict the search space in order to
      accelerate the learning process of Bayesian network. First, the proposed CAS
      algorithm automatically selects the neighbor candidates of each node before
      searching the best structure of GRN. Then based on CAS algorithm, we propose a
      globally optimal greedy search method (CAS + G), which focuses on finding the
      highest rated network structure, and a local learning method (CAS + L), which
      focuses on faster learning the structure with little loss of quality. CONCLUSION:
      Results show that the proposed CAS algorithm can effectively reduce the search
      space of Bayesian networks through identifying the neighbor candidates of each
      node. In our experiments, the CAS + G method outperforms the state-of-the-art
      method on simulation data for inferring GRNs, and the CAS + L method is
      significantly faster than the state-of-the-art method with little loss of
      accuracy. Hence, the CAS based methods effectively decrease the computational
      complexity of Bayesian network and are more suitable for GRN inference.

PMID- 29219085
TI  - Perceptions about data-informed decisions: an assessment of information-use in
      high HIV-prevalence settings in South Africa.
AB  - BACKGROUND: Information-use is an integral component of a routine health
      information system and essential to influence policy-making, program actions and
      research. Despite an increased amount of routine data collected, planning and
      resource-allocation decisions made by health managers for managing HIV programs
      are often not based on data. This study investigated the use of information, and
      barriers to using routine data for monitoring the prevention of mother-to-child
      transmission of HIV (PMTCT) programs in two high HIV-prevalence districts in
      South Africa. METHODS: We undertook an observational study using a multi-method
      approach, including an inventory of facility records and reports. The performance
      of routine information systems management (PRISM) diagnostic 'Use of Information'
      tool was used to assess the PMTCT information system for evidence of data use in
      57 health facilities in two districts. Twenty-two in-depth interviews were
      conducted with key informants to investigate barriers to information use in
      decision-making. Participants were purposively selected based on their positions
      and experience with either producing PMTCT data and/or using data for management
      purposes. We computed descriptive statistics and used a general inductive
      approach to analyze the qualitative data. RESULTS: Despite the availability of
      mechanisms and processes to facilitate information-use in about two-thirds of the
      facilities, evidence of information-use (i.e., indication of some form of
      information-use in available RHIS reports) was demonstrated in 53% of the
      facilities. Information was inadequately used at district and facility levels to
      inform decisions and planning, but was selectively used for reporting and
      monitoring program outputs at the provincial level. The inadequate use of
      information stemmed from organizational issues such as the lack of a culture of
      information-use, lack of trust in the data, and the inability of program and
      facility managers to analyze, interpret and use information. CONCLUSIONS:
      Managers' inability to use information implied that decisions for program
      implementation and improving service delivery were not always based on data. This
      lack of data use could influence the delivery of health care services negatively.
      Facility and program managers should be provided with opportunities for capacity
      development as well as practice-based, in-service training, and be supported to
      use information for planning, management and decision-making.

PMID- 29219086
TI  - Measurement and analysis of inequality of opportunity in access of maternal and
      child health care in Togo.
AB  - BACKGROUND: Access to maternal and child health care in low- and middle-income
      countries such as Togo is characterized by significant inequalities. Most studies
      in the Togolese context have examined the total inequality of health and the
      determinants of individuals' health. Few empirical studies in Togo have focused
      on inequalities of opportunity in maternal and child health. To fill this gap, we
      estimated changes in inequality of opportunity in access to maternal and child
      health services between 1998 and 2013 using data from Togo Demographic and Health
      Surveys (DHS). METHOD: We computed the Human Opportunity Index (HOI)-a measure of
      how individual, household, and geographic characteristics like sex and place of
      residence can affect individuals' access to services or goods that should be
      universal-using five indicators of access to healthcare and one composite
      indicator of access to adequate care for children. The five indicators of access
      were: birth in a public or private health facility; whether the child had
      received any vaccinations; access to prenatal care; prenatal care given by
      qualified staff; and having at least four antenatal visits. We then examined
      differences across the two years. RESULTS: Between 1998 and 2013, inequality of
      opportunities decreased for four out of six indicators. However, inequalities
      increased in access to antenatal care provided by qualified staff (5.9% to 12.5%)
      and access to adequate care (27.7% to 28.6%). CONCLUSIONS: Although inequality of
      opportunities reduced between 1998 and 2013 for some of the key maternal and
      child health indicators, the average coverage and access rates underscore the
      need for sustained efforts to ensure equitable access to primary health care for
      mothers and children.

PMID- 29219087
TI  - Canadian 24-hour movement guidelines for the early years (0-4 years): exploring
      the perceptions of stakeholders and end users regarding their acceptability,
      barriers to uptake, and dissemination.
AB  - BACKGROUND: It is important to engage stakeholders and end users in the
      development of guidelines for knowledge translation purposes. The aim of this
      study was to examine stakeholders' (experts in pediatric and family medicine,
      physical activity knowledge translation, and research) and end users' (parents
      and early childhood educators) perceptions of the Canadian 24-Hour Movement
      Guidelines for the Early Years (0-4 years). METHODS: Stakeholders (n = 10)
      engaged in telephone interviews and end users (n = 92) participated in focus
      groups (n = 14) to discuss perceived clarity and need for the guidelines,
      potential barriers to implementation, identification of credible messengers, and
      methods for dissemination of the guidelines. A thematic analysis was conducted.
      RESULTS: The proposed guidelines were very well received by both stakeholders and
      end users. A clear need for such guidelines was identified, and most believed the
      guidelines were achievable. Stakeholders and end users identified several
      potential barriers to uptake, including low awareness of current guidelines;
      'daily challenges' such as allure of screen time, lack of time, and competing
      priorities; and challenges in the context of shifting social norms. A range of
      methods and messengers of dissemination were identified. Medical and child care
      settings were the most frequently cited places for dissemination, and physicians
      and early childhood educators were the most common suggestions for messengers.
      CONCLUSIONS: There was consistent support for the Canadian 24-Hour Movement
      Guidelines for the Early Years (0-4 years) from both stakeholders and end users.
      Moving forward, it is important to dedicate appropriate support and funding
      toward dissemination efforts in order to reach end users, particularly parents
      and early childhood educators.

PMID- 29219088
TI  - The health effects of hotter summers and heat waves in the population of the
      United Kingdom: a review of the evidence.
AB  - It is widely acknowledged that the climate is warming globally and within the UK.
      In this paper, studies which assess the direct impact of current increased
      temperatures and heat-waves on health and those which project future health
      impacts of heat under different climate change scenarios in the UK are
      reviewed.This review finds that all UK studies demonstrate an increase in heat
      related mortality occurring at temperatures above threshold values, with
      respiratory deaths being more sensitive to heat than deaths from cardiovascular
      disease (although the burden from cardiovascular deaths is greater in absolute
      terms). The relationship between heat and other health outcomes such as hospital
      admissions, myocardial infarctions and birth outcomes is less consistent. We
      highlight the main populations who are vulnerable to heat. Within the UK, these
      are older populations, those with certain co-morbidities and those living in
      Greater London, the South East and Eastern regions.In all assessments of heat
      related impacts using different climate change scenarios, deaths are expected to
      increase due to hotter temperatures, with some studies demonstrating that an
      increase in the elderly population will also amplify burdens. However, key gaps
      in knowledge are found in relation to how urbanisation and population adaptation
      to heat will affect health impacts, and in relation to current and future
      strategies for effective, sustainable and equitable adaptation to heat. These and
      other key gaps in knowledge, both in terms of research needs and knowledge
      required to make sound public- health policy, are discussed.

PMID- 29219089
TI  - Health impacts of climate change and health and social inequalities in the UK.
AB  - This article examines how social and health inequalities shape the health impacts
      of climate change in the UK, and what the implications are for climate change
      adaptation and health care provision. The evidence generated by the other
      articles of the special issue were interpreted using social justice reasoning in
      light of additional literature, to draw out the key implications of health and
      social inequalities for health outcomes of climate change. Exposure to heat and
      cold, air pollution, pollen, food safety risks, disruptions to access to and
      functioning of health services and facilities, emerging infections and flooding
      are examined as the key impacts of climate change influencing health outcomes.
      Age, pre-existing medical conditions and social deprivation are found to be the
      key (but not only) factors that make people vulnerable and to experience more
      adverse health outcomes related to climate change impacts. In the future, climate
      change, aging population and decreasing public spending on health and social care
      may aggravate inequality of health outcomes related to climate change. Health
      education and public preparedness measures that take into account differential
      exposure, sensitivity and adaptive capacity of different groups help address
      health and social inequalities to do with climate change. Adaptation strategies
      based on individual preparedness, action and behaviour change may aggravate
      health and social inequalities due to their selective uptake, unless they are
      coupled with broad public information campaigns and financial support for
      undertaking adaptive measures.

PMID- 29219091
TI  - Potential impact of climate change on emerging vector-borne and other infections
      in the UK.
AB  - Climate is one of several causes of disease emergence. Although half or more of
      infectious diseases are affected by climate it appears to be a relatively
      infrequent cause of human disease emergence. Climate mostly affects diseases
      caused by pathogens that spend part of their lifecycle outside of the host,
      exposed to the environment. The most important routes of transmission of climate
      sensitive diseases are by arthropod (insect and tick) vectors, in water and in
      food. Given the sensitivity of many diseases to climate, it is very likely that
      at least some will respond to future climate change. In the case of vector-borne
      diseases this response will include spread to new areas. Several vector-borne
      diseases have emerged in Europe in recent years; these include vivax malaria,
      West Nile fever, dengue fever, Chikungunya fever, leishmaniasis, Lyme disease and
      tick-borne encephalitis. The vectors of these diseases are mosquitoes, sand flies
      and ticks. The UK has endemic mosquito species capable of transmitting malaria
      and probably other pathogens, and ticks that transmit Lyme disease. The UK is
      also threatened by invasive mosquito species known to be able to transmit West
      Nile, dengue, chikungunya and Zika, and sand flies that spread leishmaniasis.
      Warmer temperatures in the future will increase the suitability of the UK's
      climate for these invasive species, and increase the risk that they may spread
      disease. While much attention is on invasive species, it is important to
      recognize the threat presented by native species too. Proposed actions to reduce
      the future impact of emerging vector-borne diseases in the UK include insect
      control activity at points of entry of vehicles and certain goods, wider
      surveillance for mosquitoes and sand flies, research into the threat posed by
      native species, increased awareness of the medical profession of the threat posed
      by specific diseases, regular risk assessments, and increased preparedness for
      the occurrence of a disease emergency.

PMID- 29219090
TI  - Systematic review of the relationships between physical activity and health
      indicators in the early years (0-4 years).
AB  - BACKGROUND: Given the rapid development during the early years (0-4 years), an
      understanding of the health implications of physical activity is needed. The
      purpose of this systematic review was to examine the relationships between
      objectively and subjectively measured physical activity and health indicators in
      the early years. METHODS: Electronic databases were originally searched in April,
      2016. Included studies needed to be peer-reviewed, written in English or French,
      and meet a priori study criteria. The population was apparently healthy children
      aged 1 month to 59.99 months/4.99 years. The intervention/exposure was
      objectively and subjectively measured physical activity. The comparator was
      various volumes, durations, frequencies, patterns, types, and intensities of
      physical activity. The outcomes were health indicators ranked as critical
      (adiposity, motor development, psychosocial health, cognitive development,
      fitness) and important (bone and skeletal health, cardiometabolic health, and
      risks/harm). The Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) framework was used to assess the quality of evidence for each
      health indicator by each study design. RESULTS: Ninety-six studies representing
      71,291 unique participants from 36 countries were included. Physical activity
      interventions were consistently (>60% of studies) associated with improved motor
      and cognitive development, and psychosocial and cardiometabolic health. Across
      observational studies, physical activity was consistently associated with
      favourable motor development, fitness, and bone and skeletal health. For
      intensity, light- and moderate-intensity physical activity were not consistently
      associated with any health indicators, whereas moderate- to vigorous-intensity,
      vigorous-intensity, and total physical activity were consistently favourably
      associated with multiple health indicators. Across study designs, consistent
      favourable associations with health indicators were observed for a variety of
      types of physical activity, including active play, aerobic, dance, prone position
      (infants; <=1 year), and structured/organized. Apart from >=30 min/day of the
      prone position for infants, the most favourable frequency and duration of
      physical activity was unclear. However, more physical activity appeared better
      for health. Evidence ranged from "very low" to "high" quality. CONCLUSIONS:
      Specific types of physical activity, total physical activity, and physical
      activity of at least moderate- to vigorous-intensity were consistently favourably
      associated with multiple health indicators. The majority of evidence was in
      preschool-aged children (3-4 years). Findings will inform evidence-based
      guidelines.

PMID- 29219093
TI  - Feasibility of implementing a cellphone-based reminder/recall strategy to improve
      childhood routine immunization in a low-resource setting: a descriptive report.
AB  - BACKGROUND: Reminder/recall systems are effective ways to improve immunization
      rates, but their feasibility in primary health care (PHC) settings in Nigeria has
      not been adequately evaluated. In this study we describe the acceptability and
      adaptability of immunization reminder/recall system in an urban setting in
      southwest Nigeria. METHODS: This is a descriptive report of a cluster randomized
      controlled trial. Four local government areas (LGAs) were randomly assigned into
      a cellphone reminder/recall intervention group or a usual care control group.
      Within each LGA, PHC centers were purposively selected to participate in the
      study. In each PHC center, mothers and their infants aged 0-3 months were
      enrolled into the two groups during the infants' first immunization visit.
      Mothers (or other contact persons) in the intervention group received cellphone
      calls reminding them to take their child for scheduled immunizations. Follow-up
      of all the children lasted till the final scheduled immunization visit for each
      child. The intervention lasted for 13 months. RESULTS: A total of 595
      mothers/infants pairs (295 in the intervention group and 300 in the control
      group) participated in the study. Almost all mothers (n = 590, 99.2%) had access
      to their own cellphone or had access to a cellphone belonging to a significant
      other. Ninety-eight percent (n = 584) of all mothers were willing to receive
      immunization reminder/recall phone calls. Eighty-seven percent (n = 2023) of all
      calls (n = 2324) for the reminder/recall intervention went through to the
      recipients and of these calls, 1948 (96.3%) were received. The mean cost of each
      call in US Dollars was about 5 cents. Immunization compliance rate (the receipt
      of required number of doses of routine vaccines at the appropriate age at
      recommended interval) was 79.2% among the children in intervention group and
      46.4% in the control group (p < 0.001). CONCLUSION: Results demonstrate that
      cellphone reminder/recall interventions to improve routine childhood immunization
      are feasible in PHC settings in limited-resource settings with wide cellphone
      coverage, such as urban areas in Nigeria. Further research to test the potential
      for scale up in a variety of settings is recommended. TRIAL REGISTRATION:
      PACTR201702002043415 ; Date of registration: 17 February 2017. (Retrospectively
      registered).

PMID- 29219092
TI  - Systematic review of the relationships between sedentary behaviour and health
      indicators in the early years (0-4 years).
AB  - BACKGROUND: The purpose of this systematic review was to examine the
      relationships between sedentary behaviour (SB) and health indicators in children
      aged 0 to 4 years, and to determine what doses of SB (i.e., duration, patterns
      [frequency, interruptions], and type) were associated with health indicators.
      METHODS: Online databases were searched for peer-reviewed studies that met the a
      priori inclusion criteria: population (apparently healthy, 1 month to 4.99
      years), intervention/exposure and comparator (durations, patterns, and types of
      SB), and outcome/health indicator (critical: adiposity, motor development,
      psychosocial health, cognitive development; important: bone and skeletal health,
      cardiometabolic health, fitness, risks/harm). The quality of the evidence was
      assessed by study design and outcome using the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) framework. RESULTS: Due to
      heterogeneity, meta-analyses were not possible; instead, narrative syntheses were
      conducted, structured around the health indicator and type of SB. A total of 96
      studies were included (195,430 participants from 33 countries). Study designs
      were: randomized controlled trial (n = 1), case-control (n = 3), longitudinal (n
      = 25), longitudinal with additional cross-sectional analyses (n = 5), and cross
      sectional (n = 62). Evidence quality ranged from "very low" to "moderate".
      Associations between objectively measured total sedentary time and indicators of
      adiposity and motor development were predominantly null. Associations between
      screen time and indicators of adiposity, motor or cognitive development, and
      psychosocial health were primarily unfavourable or null. Associations between
      reading/storytelling and indicators of cognitive development were favourable or
      null. Associations between time spent seated (e.g., in car seats or strollers) or
      in the supine position, and indicators of adiposity and motor development, were
      primarily unfavourable or null. Data were scarce for other outcomes. CONCLUSIONS:
      These findings continue to support the importance of minimizing screen time for
      disease prevention and health promotion in the early years, but also highlight
      the potential cognitive benefits of interactive non-screen-based sedentary
      behaviours such as reading and storytelling. Additional high-quality research
      using valid and reliable measures is needed to more definitively establish the
      relationships between durations, patterns, and types of SB and health indicators,
      and to provide insight into the appropriate dose of SB for optimal health in the
      early years.

PMID- 29219094
TI  - A collaborative approach to adopting/adapting guidelines - The Australian 24-Hour
      Movement Guidelines for the early years (Birth to 5 years): an integration of
      physical activity, sedentary behavior, and sleep.
AB  - BACKGROUND: In 2017, the Australian Government funded the update of the National
      Physical Activity Recommendations for Children 0-5 years, with the intention that
      they be an integration of movement behaviours across the 24-h period. The benefit
      for Australia was that it could leverage research in Canada in the development of
      their 24-h guidelines for the early years. Concurrently, the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) working group
      published a model to produce guidelines based on adoption, adaption and/or de
      novo development using the GRADE evidence-to-decision framework. Referred to as
      the GRADE-ADOLOPMENT approach, it allows guideline developers to follow a
      structured and transparent process in a more efficient manner, potentially
      avoiding the need to unnecessarily repeat costly tasks such as conducting
      systematic reviews. The purpose of this paper is to outline the process and
      outcomes for adapting the Canadian 24-Hour Movement Guidelines for the Early
      Years to develop the Australian 24-Hour Movement Guidelines for the Early Years
      guided by the GRADE-ADOLOPMENT framework. METHODS: The development process was
      guided by the GRADE-ADOLOPMENT approach. A Leadership Group and Consensus Panel
      were formed and existing credible guidelines identified. The draft Canadian 24-h
      integrated movement guidelines for the early years best met the criteria
      established by the Panel. These were evaluated based on the evidence in the GRADE
      tables, summaries of findings tables and draft recommendations from the Canadian
      Draft Guidelines. Updates to each of the Canadian systematic reviews were
      conducted and the Consensus Panel reviewed the evidence for each behaviour
      separately and made a decision to adopt or adapt the Canadian recommendations for
      each behaviour or create de novo recommendations. An online survey was then
      conducted (n = 302) along with five focus groups (n = 30) and five key informant
      interviews (n = 5) to obtain feedback from stakeholders on the draft guidelines.
      RESULTS: Based on the evidence from the Canadian systematic reviews and the
      updated systematic reviews in Australia, the Consensus Panel agreed to adopt the
      Canadian recommendations and, apart from some minor changes to the wording of
      good practice statements, keep the wording of the guidelines, preamble and title
      of the Canadian Guidelines. The Australian Guidelines provide evidence-informed
      recommendations for a healthy day (24-h), integrating physical activity,
      sedentary behaviour (including limits to screen time), and sleep for infants (<1
      year), toddlers (1-2 years) and preschoolers (3-5 years). CONCLUSIONS: To our
      knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been
      used. Following this approach, the judgments of the Australian Consensus Panel
      did not differ sufficiently to change the directions and strength of the
      recommendations and as such, the Canadian recommendations were adopted with very
      minor alterations. This allowed the Guidelines to be developed much faster and at
      lower cost. As such, we would recommend the GRADE-ADOLOPMENT approach, especially
      if a credible set of guidelines, with all supporting materials and developed
      using a transparent process, is available. Other countries may consider using
      this approach when developing and/or revising national movement guidelines.

PMID- 29219095
TI  - Compliance with the Australian 24-hour movement guidelines for the early years:
      associations with weight status.
AB  - BACKGROUND: For effective public health and surveillance it is important to
      document the proportion of young children who meet the new Australian Integrated
      24 h Movement Guidelines for the Early Years and how these associate with health
      outcomes. We aimed to (i) assess compliance with the new Integrated 24 h Movement
      Guidelines for the Early Years in a sample of Australian toddlers; and (ii)
      ascertain whether compliance with the guidelines associates with weight status.
      METHODS: The sample comprised 202 toddlers (104 girls) aged 19.74 +/- 4.07 months
      from the GET UP! STUDY: Participants wore accelerometers (Actigraph GT3X+) for 24
      h over 7 consecutive days to assess physical activity, sedentary time and sleep.
      Parents reported participants' screen time. Weight and height were measured and
      body mass index (BMI) z-scores by age and sex were calculated. Analysis of
      Covariance (ANCOVA) was performed to test differences in BMI z-scores between
      participants complying with (i) none or any individual guideline, (ii) any
      combination of meeting two guidelines, and (iii) those who met all three
      guidelines, adjusting for child age, gender and socioeconomic status. RESULTS:
      Only 8.9% of the sample met the overall 24 h movement guidelines. Most of the
      sample met the physical activity (96.5%) and sleep (79.7%) guidelines but only
      11.4% met the sedentary behavior guideline. Average BMI Z-scores did not
      significantly differ between children who complied with none or any individual
      guideline, any combination of meeting two guidelines, and those who met all three
      guidelines (p > 0.05). Although the lack of significant differences, participants
      who accomplished any combination of two guidelines or all three guidelines appear
      to have had a lower BMI Z-score than those complying with one of the guidelines
      or none. CONCLUSIONS: Just under 9% of our sample met the overall Australian 24 h
      Movement Guidelines for the Early Years. BMI was not associated with the
      accomplishment of any of the 24-h Movement Guidelines. Strategies to promote
      adherence to the 24-h movement guidelines in toddlers, particularly for screen
      time, are necessary, as promoting health-related behaviors in early childhood has
      the potential to provide children a strong foundation for lifelong physical and
      mental health.

PMID- 29219096
TI  - Meeting new Canadian 24-Hour Movement Guidelines for the Early Years and
      associations with adiposity among toddlers living in Edmonton, Canada.
AB  - BACKGROUND: Canada has recently released guidelines that include toddler-specific
      recommendations for physical activity, screen-based sedentary behaviour, and
      sleep. This study examined the proportions of toddlers meeting the new Canadian
      24-Hour Movement Guidelines for the Early Years (0-4 years) and associations with
      body mass index (BMI) z-scores in a sample from Edmonton, Canada. METHODS:
      Participants included 151 toddlers (aged 19.0 +/- 1.9 months) for whom there was
      complete objectively measured physical activity data from the Parents' Role in
      Establishing healthy Physical activity and Sedentary behaviour habits (PREPS)
      project. Toddlers' physical activity was measured using ActiGraph wGT3X-BT
      monitors. Toddlers' screen time and sleep were measured using the PREPS
      questionnaire. Toddlers' height and weight were objectively measured by public
      health nurses and BMI z-scores were calculated using World Health Organization
      growth standards. Meeting the overall 24-Hour Movement Guidelines was defined as:
      >=180 min/day of total physical activity, including >=1 min/day of moderate- to
      vigorous-intensity physical activity; no screen time per day (for those aged 12
      23 months) or <=1 h/day of screen time per day (ages 24-35 months); and 11-14 h
      of sleep per 24-h period. Frequency analyses and linear regression models were
      conducted. RESULTS: Only 11.9% of toddlers met the overall 24-Hour Movement
      Guidelines, but this finding was largely driven by screen time. The majority of
      toddlers met the individual physical activity (99.3%) and sleep (82.1%)
      recommendations, while only 15.2% of toddlers met the screen time recommendation.
      No associations were observed between meeting specific and general combinations
      of recommendations within the guidelines and BMI z-scores. CONCLUSIONS: Most
      toddlers in this sample were meeting physical activity and sleep recommendations
      but were engaging in more screen time than recommended. Consequently, only a
      small proportion of toddlers met the overall guidelines. Based on the findings of
      this study, identifying modifiable correlates of screen time to inform
      appropriate strategies to reduce screen time appears key for increasing the
      proportion of toddlers meeting the 24-Hour Movement Guidelines for the Early
      Years. Future research should examine the associations between meeting the new
      guidelines and other health indicators. Furthermore, future high-quality studies
      examining dose-response relationships between movement behaviours and health
      indicators are needed to inform guideline updates.

PMID- 29219097
TI  - Analysis of the impact of healthcare support initiatives for physically disabled
      people on their access to care in the city of Saint-Louis, Senegal.
AB  - BACKGROUND: People with disabilities represent approximately 6% of the Senegalese
      population. They face significant barriers to accessing health care. Although
      several initiatives have been implemented to improve access to health care for
      this vulnerable population, few studies have examined the effects of these
      initiatives. We conducted a mixed methods study in three neighborhoods in Saint
      Louis City (Senegal) to assess the impact of health systems and social assistance
      programs aimed at improving access to health care for people with disabilities.
      METHODS: Data were collected from 105 people living with disabilities aged 1-49
      years (or their caregivers). Interviews were also conducted with key stakeholders
      in the health and welfare sectors. Global Positioning System (GPS) coordinates of
      all the health and social services within the city were obtained. We also
      conducted observations in the main regional hospital, the district health center
      and three level-one health facilities to assess physical accessibility as well as
      interactions between patients living with disabilities and health and social
      workers. Descriptive and multivariate analyses were performed using Sphinx
      software. Spatial data were used to make cartographic representations of the
      proximity to basic social services using Arc GIS software. RESULTS: Seventy-nine
      percent of survey respondents reported difficulty obtaining treatment. Key
      barriers to care included the high cost of care, as well as ill-treatment by
      health workers. Limited human resources and low levels of financial support,
      combined with logistical challenges were reported to hamper the success of social
      welfare initiatives that aim to facilitate access to health care for people with
      disabilities. CONCLUSION: Our results suggest that initiatives to increase access
      to health care among people with disability in Saint-Louis have had limited
      impact. Study findings underscore the importance of strengthening social
      assistance schemes within the health system and the need for social workers and
      health workers to collaborate to improve access to health care for people with
      disabilities.

PMID- 29219098
TI  - Analyzing implementation dynamics using theory-driven evaluation principles:
      lessons learnt from a South African centralized chronic dispensing model.
AB  - BACKGROUND: Centralized dispensing of essential medicines is one of South
      Africa's strategies to address the shortage of pharmacists, reduce patients'
      waiting times and reduce over-crowding at public sector healthcare facilities.
      This article reports findings of an evaluation of the Chronic Dispensing Unit
      (CDU) in one province. The objectives of this process evaluation were to: (1)
      compare what was planned versus the actual implementation and (2) establish the
      causal elements and contextual factors influencing implementation. METHODS: This
      qualitative study employed key informant interviews with the intervention's
      implementers (clinicians, managers and the service provider) [N = 40], and a
      review of policy and program documents. Data were thematically analyzed by
      identifying the main influences shaping the implementation process. Theory-driven
      evaluation principles were applied as a theoretical framework to explain
      implementation dynamics. RESULTS: The overall participants' response about the
      CDU was positive and the majority of informants concurred that the establishment
      of the CDU to dispense large volumes of medicines is a beneficial strategy to
      address healthcare barriers because mechanical functions are automated and
      distribution of medicines much quicker. However, implementation was influenced by
      the context and discrepancies between planned activities and actual
      implementation were noted. Procurement inefficiencies at central level caused
      medicine stock-outs and affected CDU activities. At the frontline, actors were
      aware of the CDU's implementation guidelines regarding patient selection,
      prescription validity and management of non-collected medicines but these were
      adapted to accommodate practical realities and to meet performance targets
      attached to the intervention. Implementation success was a result of a
      combination of 'hardware' (e.g. training, policies, implementation support and
      appropriate infrastructure) and 'software' (e.g. ownership, cooperation between
      healthcare practitioners and trust) factors. CONCLUSION: This study shows that
      health system interventions have unpredictable paths of implementation.
      Discrepancies between planned and actual implementation reinforce findings in
      existing literature suggesting that while tools and defined operating procedures
      are necessary for any intervention, their successful application depends
      crucially on the context and environment in which implementation occurs. We
      anticipate that this evaluation will stimulate wider thinking about the
      implementation of similar models in low- and middle-income countries.

PMID- 29219099
TI  - Scoping the proximal and distal dimensions of climate change on health and
      wellbeing.
AB  - The impacts of climate on health and wellbeing occur in time and space and
      through a range of indirect, complicated mechanisms. This diversity of pathways
      has major implications for national public health planning and influence on
      interventions that might help to mitigate and adapt to rapidly changing
      environmental conditions, nationally and internationally. This paper draws upon
      evidence from public health and adverse impact studies across climate science,
      hydrology, agriculture, public health, and the social sciences. It presents a
      conceptual model to support decision-making by recognizing both the proximal and
      distal pathways from climate-induced environmental change to national health and
      wellbeing. The proximal and distal pathways associated with food security,
      migration and mobility illustrate the diverse climate change influences in
      different geographic locations over different timescales. We argue that greater
      realization and articulation of proximal and distal pathways should radically
      alter how climate change is addressed as a national and international public
      health challenge.

PMID- 29219100
TI  - Food-borne disease and climate change in the United Kingdom.
AB  - This review examined the likely impact of climate change upon food-borne disease
      in the UK using Campylobacter and Salmonella as example organisms. Campylobacter
      is an important food-borne disease and an increasing public health threat. There
      is a reasonable evidence base that the environment and weather play a role in its
      transmission to humans. However, uncertainty as to the precise mechanisms through
      which weather affects disease, make it difficult to assess the likely impact of
      climate change. There are strong positive associations between Salmonella cases
      and ambient temperature, and a clear understanding of the mechanisms behind this.
      However, because the incidence of Salmonella disease is declining in the UK, any
      climate change increases are likely to be small. For both Salmonella and
      Campylobacter the disease incidence is greatest in older adults and young
      children. There are many pathways through which climate change may affect food
      but only a few of these have been rigorously examined. This provides a high
      degree of uncertainty as to what the impacts of climate change will be. Food is
      highly controlled at the National and EU level. This provides the UK with
      resilience to climate change as well as potential to adapt to its consequences
      but it is unknown whether these are sufficient in the context of a changing
      climate.

PMID- 29219101
TI  - Health effects of milder winters: a review of evidence from the United Kingdom.
AB  - Cold-related mortality and morbidity remains an important public health problem
      in the UK and elsewhere. Health burdens have often reported to be higher in the
      UK compared to other countries with colder climates, however such assessments are
      usually based on comparison of excess winter mortality indices, which are subject
      to biases. Daily time-series regression or case-crossover studies provide the
      best evidence of the acute effects of cold exposure. Such studies report a 6%
      increase in all-cause deaths in England & Wales for every 1  degrees C fall in
      daily mean temperature within the top 5% of the coldest days. In major Scottish
      cities, a 1  degrees C reduction in mean temperature below 11  degrees C was
      associated with an increase in mortality of 2.9%, 3.4%, 4.8% and 1.7% from all
      causes, cardiovascular, respiratory, and non-cardio-respiratory causes
      respectively. In Northern Ireland, a 1  degrees C fall during winter months led
      to increases of 4.5%, 3.9% and 11.2% for all-cause, cardiovascular and
      respiratory deaths respectively among adults. Raised risks are also observed with
      morbidity outcomes. Hip fractures among the elderly are only weakly associated
      with snow and ice conditions in the UK, with the majority of cases occurring
      indoors. A person's susceptibility to cold weather is affected by both individual
      and contextual-level risk factors. Variations in the distributions of health,
      demographic, socio-economic and built-environment characteristics are likely to
      explain most differences in cold risk observed between UK regions. Although cold
      related health impacts reduced throughout much of the previous century in UK
      populations, there is little evidence on the contribution that milder winters due
      to climate change may have made to reductions in more recent decades.
      Intervention measures designed to minimise cold exposure and reduce fuel poverty
      will likely play a key role in determining current and future health burdens
      associated with cold weather.

PMID- 29219102
TI  - Canadian 24-Hour Movement Guidelines for the Early Years (0-4 years): An
      Integration of Physical Activity, Sedentary Behaviour, and Sleep.
AB  - BACKGROUND: The Canadian Society for Exercise Physiology convened representatives
      of national organizations, research experts, methodologists, stakeholders, and
      end-users who followed rigorous and transparent guideline development procedures
      to create the Canadian 24-Hour Movement Guidelines for the Early Years (0-4
      years): An Integration of Physical Activity, Sedentary Behaviour, and Sleep.
      These novel guidelines for children of the early years embrace the natural and
      intuitive integration of movement behaviours across the whole day (24-h period).
      METHODS: The development process was guided by the Appraisal of Guidelines for
      Research and Evaluation (AGREE) II instrument. Four systematic reviews (physical
      activity, sedentary behaviour, sleep, combined behaviours) examining the
      relationships within and among movement behaviours and several health indicators
      were completed and interpreted by a Guideline Development Panel. The systematic
      reviews that were conducted to inform the development of the guidelines, and the
      framework that was applied to develop the recommendations, followed the Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
      Complementary compositional analyses were performed using data from the Canadian
      Health Measures Survey to examine the relationships between movement behaviours
      and indicators of adiposity. A review of the evidence on the cost effectiveness
      and resource use associated with the implementation of the proposed guidelines
      was also undertaken. A stakeholder survey (n = 546), 10 key informant interviews,
      and 14 focus groups (n = 92 participants) were completed to gather feedback on
      draft guidelines and their dissemination. RESULTS: The guidelines provide
      evidence-informed recommendations as to the combinations of light-, moderate- and
      vigorous-intensity physical activity, sedentary behaviours, and sleep that
      infants (<1 year), toddlers (1-2 years) and preschoolers (3-4 years) should
      achieve for a healthy day (24 h). Proactive dissemination, promotion,
      implementation, and evaluation plans were prepared to optimize uptake and
      activation of the new guidelines. CONCLUSIONS: These guidelines represent a
      sensible evolution of public health guidelines whereby optimal health is framed
      within the balance of movement behaviours across the whole day, while respecting
      preferences of end-users. Future research should consider the integrated
      relationships among movement behaviours, and similar integrated guidelines for
      other age groups should be developed.

PMID- 29219103
TI  - Climate change impacts on human health over Europe through its effect on air
      quality.
AB  - This review examines the current literature on the effects of future emissions
      and climate change on particulate matter (PM) and O3 air quality and on the
      consequent health impacts, with a focus on Europe. There is considerable
      literature on the effects of climate change on O3 but fewer studies on the
      effects of climate change on PM concentrations. Under the latest
      Intergovernmental Panel on Climate Change (IPCC) 5th assessment report (AR5)
      Representative Concentration Pathways (RCPs), background O3 entering Europe is
      expected to decrease under most scenarios due to higher water vapour
      concentrations in a warmer climate. However, under the extreme pathway RCP8.5
      higher (more than double) methane (CH4) abundances lead to increases in
      background O3 that offset the O3 decrease due to climate change especially for
      the 2100 period. Regionally, in polluted areas with high levels of nitrogen
      oxides (NOx), elevated surface temperatures and humidities yield increases in
      surface O3 - termed the O3 climate penalty - especially in southern Europe. The
      O3 response is larger for metrics that represent the higher end of the O3
      distribution, such as daily maximum O3. Future changes in PM concentrations due
      to climate change are much less certain, although several recent studies also
      suggest a PM climate penalty due to high temperatures and humidity and reduced
      precipitation in northern mid-latitude land regions in 2100.A larger number of
      studies have examined both future climate and emissions changes under the RCP
      scenarios. Under these pathways the impact of emission changes on air quality out
      to the 2050s will be larger than that due to climate change, because of large
      reductions in emissions of O3 and PM pollutant precursor emissions and the more
      limited climate change response itself. Climate change will also affect climate
      extreme events such as heatwaves. Air pollution episodes are associated with
      stagnation events and sometimes heat waves. Air quality during the 2003 heatwave
      over Europe has been examined in numerous studies and mechanisms for enhancing O3
      have been identified.There are few studies on health effects associated with
      climate change impacts alone on air quality, but these report higher O3-related
      health burdens in polluted populated regions and greater PM2.5 health burdens in
      these emission regions. Studies that examine the combined impacts of climate
      change and anthropogenic emissions change under the RCP scenarios report
      reductions in global and European premature O3-respiratory related and PM
      mortalities arising from the large decreases in precursor emissions. Under RCP
      8.5 the large increase in CH4 leads to global and European excess O3-respiratory
      related mortalities in 2100. For future health effects, besides uncertainty in
      future O3 and particularly PM concentrations, there is also uncertainty in risk
      estimates such as effect modification by temperature on pollutant-response
      relationships and potential future adaptation that would alter exposure risk.

PMID- 29219104
TI  - Adherence to 24-Hour Movement Guidelines for the Early Years and associations
      with social-cognitive development among Australian preschool children.
AB  - BACKGROUND: The new Australian 24-Hour Movement Guidelines for the Early Years
      recommend that, for preschoolers, a healthy 24-h includes: i) >=180 min of
      physical activity, including >=60 min of energetic play, ii) <=1 h of sedentary
      screen time, and iii) 10-13 h of good quality sleep. Using an Australian sample,
      this study reports the proportion of preschool children meeting these guidelines
      and investigates associations with social-cognitive development. METHODS: Data
      from 248 preschool children (mean age = 4.2 +/- 0.6 years, 57% boys)
      participating in the PATH-ABC study were analyzed. Children completed direct
      assessments of physical activity (accelerometry) and social cognition (the Test
      of Emotional Comprehension (TEC) and Theory of Mind (ToM)). Parents reported on
      children's screen time and sleep. Children were categorised as meeting/not
      meeting: i) individual guidelines, ii) combinations of two guidelines, or iii)
      all three guidelines. Associations were examined using linear regression
      adjusting for child age, sex, vocabulary, area level socio-economic status and
      childcare level clustering. RESULTS: High proportions of children met the
      physical activity (93.1%) and sleep (88.7%) guidelines, whereas fewer met the
      screen time guideline (17.3%). Overall, 14.9% of children met all three
      guidelines. Children meeting the sleep guideline performed better on TEC than
      those who did not (mean difference [MD] = 1.41; 95% confidence interval (CI) =
      0.36, 2.47). Children meeting the sleep and physical activity or sleep and screen
      time guidelines also performed better on TEC (MD = 1.36; 95% CI = 0.31, 2.41) and
      ToM (MD = 0.25; 95% CI = -0.002, 0.50; p = 0.05), respectively, than those who
      did not. Meeting all three guidelines was associated with better ToM performance
      (MD = 0.28; 95% CI = -0.002, 0.48, p = 0.05), while meeting a larger number of
      guidelines was associated with better TEC (3 or 2 vs. 1/none, p < 0.02) and ToM
      performance (3 vs. 2, p = 0.03). CONCLUSIONS: Strategies to promote adherence to
      the 24-Hour Movement Behaviour Guidelines for the Early Years among preschool
      children are warranted. Supporting preschool children to meet all guidelines or
      more guidelines, particularly the sleep and screen time guidelines, may be
      beneficial for their social-cognitive development.

PMID- 29219106
TI  - Notification that new names of prokaryotes, new combinations and new taxonomic
      opinions have appeared in volume 67, part 9, of the IJSEM.

PMID- 29219105
TI  - Impact of extreme weather events and climate change for health and social care
      systems.
AB  - This review, commissioned by the Research Councils UK Living With Environmental
      Change (LWEC) programme, concerns research on the impacts on health and social
      care systems in the United Kingdom of extreme weather events, under conditions of
      climate change. Extreme weather events considered include heatwaves, coldwaves
      and flooding. Using a structured review method, we consider evidence regarding
      the currently observed and anticipated future impacts of extreme weather on
      health and social care systems and the potential of preparedness and adaptation
      measures that may enhance resilience. We highlight a number of general
      conclusions which are likely to be of international relevance, although the
      review focussed on the situation in the UK. Extreme weather events impact the
      operation of health services through the effects on built, social and
      institutional infrastructures which support health and health care, and also
      because of changes in service demand as extreme weather impacts on human health.
      Strategic planning for extreme weather and impacts on the care system should be
      sensitive to within country variations. Adaptation will require changes to built
      infrastructure systems (including transport and utilities as well as individual
      care facilities) and also to institutional and social infrastructure supporting
      the health care system. Care sector organisations, communities and individuals
      need to adapt their practices to improve resilience of health and health care to
      extreme weather. Preparedness and emergency response strategies call for action
      extending beyond the emergency response services, to include health and social
      care providers more generally.

PMID- 29219107
TI  - Molecular Methods for Detection of Antimicrobial Resistance.
AB  - The increase in bacteria harboring antimicrobial resistance (AMR) is a global
      problem because there is a paucity of antibiotics available to treat multidrug
      resistant bacterial infections in humans and animals. Detection of AMR present in
      bacteria that may pose a threat to veterinary and public health is routinely
      performed using standardized phenotypic methods. Molecular methods are often used
      in addition to phenotypic methods but are set to replace them in many
      laboratories due to the greater speed and accuracy they provide in detecting the
      underlying genetic mechanism(s) for AMR. In this article we describe some of the
      common molecular methods currently used for detection of AMR genes. These include
      PCR, DNA microarray, whole-genome sequencing and metagenomics, and matrix
      assisted laser desorption ionization-time of flight mass spectrometry. The
      strengths and weaknesses of these methods are discussed, especially in the
      context of implementing them for routine surveillance activities on a global
      scale for mitigating the risk posed by AMR worldwide. Based on current popularity
      and ease of use, PCR and single-isolate whole-genome sequencing seem
      irreplaceable.

PMID- 29219108
TI  - Origin, History, and Meanings of the Word Transmission.
AB  - The origin of the words transmit and transmission and their derivatives can be
      traced to the Latin transmittere, in turn formed by prefixing the preposition
      trans ("across or beyond") to the verb mittere ("to let go or to send"). From the
      times of Ancient Rome in the 3rd century b.c.e., the Latin word transmissio has
      been "transmitted" (through Romance languages such as French, Italian, Spanish,
      and Portuguese) to all the major languages of culture, English among them. And
      through English, the international language of biomedical science in the 21st
      century, the term transmission is increasingly present today in some of the most
      dynamic disciplines of modern natural science, including genomics, molecular
      microbiology, hospital epidemiology, molecular genetics, biotechnology,
      evolutionary biology, and systems biology.

PMID- 29219109
TI  - Antimicrobial Resistance in Corynebacterium spp., Arcanobacterium spp., and
      Trueperella pyogenes.
AB  - There is currently only limited information on the antimicrobial susceptibility
      and resistance of Corynebacterium spp., Arcanobacterium spp., and Trueperella
      pyogenes from animals. The comparability of the data is hampered by the use of
      different antimicrobial susceptibility testing methods and interpretive criteria.
      To date, standard broth microdilution methods and clinical breakpoints that are
      approved by the Clinical and Laboratory Standards Institute and are applicable to
      Corynebacterium spp., Arcanobacterium spp., and T. pyogenes are available. The
      lack of species-specific clinical breakpoints for the different animal species
      reduces the explanatory power of the data. Among the isolates of the three
      genera, elevated MICs for different classes of antimicrobial agents (e.g., beta
      lactams, macrolides, lincosamides, tetracyclines, aminoglycosides, phenicols,
      sulfonamides/diaminopyrimidines, and fluoroquinolones) have been described. The
      most comprehensive data set is available for T. pyogenes, which also includes
      information about genes and mutations involved in antimicrobial resistance. In T.
      pyogenes isolates, the macrolide-lincosamide-streptogramin B resistance genes
      erm(B) and erm(X) were identified. Tetracycline resistance in T. pyogenes was
      based on the resistance genes tet(W), tet(Z), and tet(33), whereas the
      aminoglycoside resistance genes aacC, aadA1, aadA2, aadA5, aadA24, and aadB have
      been described in T. pyogenes. So far, only single genes conferring either
      phenicol resistance (cmlA6), trimethoprim resistance (dfrB2a), or beta-lactam
      resistance (blaP1) are known to occur in T. pyogenes isolates. Various 23S rRNA
      mutations, including A2058T, A2058G, and G2137C, were identified in
      macrolide/lincosamide-resistant T. pyogenes.

PMID- 29219110
TI  - Molecular identification of Trichinella species by multiplex PCR: new insight for
      Trichinella murrelli.
AB  - In order to identify Trichinella at the species level, the commonly used test is
      a multiplex PCR, allowing the discrimination of nine out of the twelve taxa
      described so far. This test is based on five primer pairs amplifying fragments of
      the large subunit rDNA. Each taxon produces one or two bands of different sizes,
      resulting in a specific band pattern. By multiplex PCR, Trichinella murrelli
      shows two bands of 127 bp and 316 bp. However, a third band of 256 bp can occur.
      This band can lead to misidentification, since it is similar to the 253 bp band
      displayed by Trichinella britovi. BLAST analysis confirmed that the 256 bp band
      is from T. murrelli. The aim of this short note is to inform analysts that T.
      murrelli larvae may display either two- or three-band patterns.

PMID- 29219111
TI  - Uterine Mass and Menorrhagia: A Rare Presentation of Acute Myeloid Leukemia with
      Arduous Clinical Course

PMID- 29219112
TI  - Haploinsufficiency of the DMRT Gene Cluster in a Case with 46,XY Ovotesticular
      Disorder of Sexual Development
AB  - Background: Ovotesticular disorder is characterized by the presence of testicular
      and ovarian tissues in the same individual. Single gene mutations in SRY, SOX9,
      DMRT1 and DAX1 can lead to ovotesticular disorder of sexual development. Case
      Report: Herein, we report a 3-month-old phenotypically female baby in whom
      differentiated tissues of both Mullerian and Wolffian ducts were detected on
      pathological analysis of laparoscopic biopsy material. Chromosomal analysis
      observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the
      DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic
      hybridisation. Conclusion: In support of previous literature, we found that
      haploinsufficiency of the DMRT gene cluster leads to ovotesticular disorder of
      sexual development. In addition, we emphasize that array comparative genomic
      hybridisation is an important technique in the molecular diagnosis of
      ovotesticular disorder of sexual.

PMID- 29219113
TI  - MicroRNA Expression Profile in the Prenatal Amniotic Fluid Samples of Pregnant
      Women with Down Syndrome.
AB  - BACKGROUND: Down syndrome, which is the most common human chromosomal anomaly
      that can affect people of any race and age, can be diagnosed prenatally in most
      cases. Prenatal diagnosis via culture method is time-consuming; thus, genetic
      analysis has thus been introduced and is continually being developed for rapid
      prenatal diagnosis. For this reason, the effective use of microRNA profiling for
      the rapid analysis of prenatal amniotic fluid samples for the diagnosis of Down
      syndrome was investigated. AIMS: To evaluate the expression levels of 14
      microRNAs encoded by chromosome 21 in amniotic fluid samples and their utility
      for prenatal diagnosis of Down syndrome. STUDY DESIGN: Case-control study.
      METHODS: We performed invasive prenatal testing for 56 pregnant women; 23 carried
      fetuses with Down syndrome, and 33 carried fetuses with a normal karyotype.
      Advanced maternal age and increased risk for Down syndrome in the screening tests
      were indications for invasive prenatal testing. The age of gestation in the study
      and control groups ranged between 17 and 18 weeks. The expression levels of
      microRNA were measured by real-time polymerase chain reaction. RESULTS: The
      expression levels of microRNA-125b-2, microRNA-155, and microRNA-3156 were
      significantly higher in the study group than in the control group. CONCLUSION:
      The presence of significantly dysregulated microRNAs may be associated with
      either the phenotype or the result of abnormal development. Further large-scale
      comparative studies conducted in a variety of conditions may bring novel insights
      in the field of abnormal prenatal conditions.

PMID- 29219115
TI  - Thermal annealing and pressure effects on BaFe2-x Co x As2 single crystals.
AB  - We investigate the pressure and thermal annealing effects on BaFe2-x Co x As2 (Co
      Ba122) single crystals with x  =  0.1 and 0.17 via electrical transport
      measurements. The thermal annealing treatment not only enhances the
      superconducting transition temperature (T c) from 9.6 to 12.7 K for x  =  0.1 and
      from 18.1 to 21.0 K for x  =  0.17, but also increases the antiferromagnetic
      transition temperature (T N). Simultaneous enhancement of T c and T N by the
      thermal annealing treatment indicates that thermal annealing could substantially
      improve the quality of the Co-doped Ba122 samples. Interestingly, T c of the Co
      Ba122 compounds shows a scaling behavior with a linear dependence on the
      resistivity value at 290 K, irrespective of tuning parameters such as chemical
      doping, pressure, and thermal annealing. These results not only provide an
      effective way to access the intrinsic properties of the BaFe2As2 system, but may
      also shed a light on designing new materials with higher superconducting
      transition temperature.

PMID- 29219116
TI  - Introducing a model of pairing based on base pair specific interactions between
      identical DNA sequences.
AB  - At present, there have been suggested two types of physical mechanism that may
      facilitate preferential pairing between DNA molecules, with identical or similar
      base pair texts, without separation of base pairs. One mechanism solely relies on
      base pair specific patterns of helix distortion being the same on the two
      molecules, discussed extensively in the past. The other mechanism proposes that
      there are preferential interactions between base pairs of the same composition.
      We introduce a model, built on this second mechanism, where both thermal
      stretching and twisting fluctuations are included, as well as the base pair
      specific helix distortions. Firstly, we consider an approximation for weak
      pairing interactions, or short molecules. This yields a dependence of the energy
      on the square root of the molecular length, which could explain recent
      experimental data. However, analysis suggests that this approximation is no
      longer valid at large DNA lengths. In a second approximation, for long molecules,
      we define two adaptation lengths for twisting and stretching, over which the
      pairing interaction can limit the accumulation of helix disorder. When the
      pairing interaction is sufficiently strong, both adaptation lengths are finite;
      however, as we reduce pairing strength, the stretching adaptation length remains
      finite but the torsional one becomes infinite. This second state persists to
      arbitrarily weak values of the pairing strength; suggesting that, if the
      molecules are long enough, the pairing energy scales as length. To probe
      differences between the two pairing mechanisms, we also construct a model of
      similar form. However, now, pairing between identical sequences solely relies on
      the intrinsic helix distortion patterns. Between the two models, we see
      interesting qualitative differences. We discuss our findings, and suggest new
      work to distinguish between the two mechanisms.

PMID- 29219114
TI  - Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO
      101 improves chronic microelectrode performance.
AB  - OBJECTIVE: Neuroinflammatory mechanisms are hypothesized to contribute to
      intracortical microelectrode failures. The cluster of differentiation 14 (CD14)
      molecule is an innate immunity receptor involved in the recognition of pathogens
      and tissue damage to promote inflammation. The goal of the study was to
      investigate the effect of CD14 inhibition on intracortical microelectrode
      recording performance and tissue integration. APPROACH: Mice implanted with
      intracortical microelectrodes in the motor cortex underwent electrophysiological
      characterization for 16 weeks, followed by endpoint histology. Three conditions
      were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3)
      wildtype control mice administered a small molecule inhibitor to CD14 called IAXO
      101. MAIN RESULTS: The CD14 knockout mice exhibited acute but not chronic
      improvements in intracortical microelectrode performance without significant
      differences in endpoint histology. Mice receiving IAXO-101 exhibited significant
      improvements in recording performance over the entire 16 week duration without
      significant differences in endpoint histology. SIGNIFICANCE: Full removal of CD14
      is beneficial at acute time ranges, but limited CD14 signaling is beneficial at
      chronic time ranges. Innate immunity receptor inhibition strategies have the
      potential to improve long-term intracortical microelectrode performance.

PMID- 29219117
TI  - Prediction of radiation necrosis in a rodent model using magnetic resonance
      imaging apparent transverse relaxation (R<sub>2</sub><sup>*</sup>).
AB  - BACKGROUND AND PURPOSE: Radiation necrosis remains an irreversible long-term side
      effect following radiotherapy to the brain. The ability to predict areas that
      could ultimately develop into necrosis could lead to prevention and management of
      radiation necrosis.&#13; Materials and Methods: Fischer 344 rats were irradiated
      using two platforms (micro-CT irradiator and x-RAD 225 IGRT) with radiation up to
      30 Gy for the micro-CT and 40 Gy for the xRAD-224 to half the brain. Animals were
      subsequently imaged using a 9.4T MRI scanner every 2-4 weeks for up to 28 weeks
      using a 7-echo gradient echo sequence. The apparent transverse relaxation
      constant (R2*) was calculated and retrospectively analyzed.&#13; Results: Animals
      irradiated with the low-dose rate micro-CT did not exhibit and symptoms or
      imaging changes associated with RN. Animals irradiated with the xRAD-225
      exhibited imaging changes consistent with RN at week 24. Analysis of the R2*
      coefficient within the lesion and hippocampus shows the potential for detection
      of RN up to 10 weeks prior to morphological changes.&#13; Conclusions: The
      ability to predict areas of RN and increases of R2* within the hippocampus
      provides a method for long-term monitoring and prediction of RN.

PMID- 29219118
TI  - Adaptive quantization of local field potentials for wireless implants in freely
      moving animals: an open-source neural recording device.
AB  - OBJECTIVE: Modern neuroscience research requires electrophysiological recording
      of local field potentials (LFPs) in moving animals. Wireless transmission has the
      advantage of removing the wires between the animal and the recording equipment
      but is hampered by the large number of data to be sent at a relatively high rate.
      APPROACH: To reduce transmission bandwidth, we propose an encoder/decoder scheme
      based on adaptive non-uniform quantization. Our algorithm uses the current
      transmitted codeword to adapt the quantization intervals to changing statistics
      in LFP signals. It is thus backward adaptive and does not require the sending of
      side information. The computational complexity is low and similar at the encoder
      and decoder sides. These features allow for real-time signal recovery and
      facilitate hardware implementation with low-cost commercial microcontrollers.
      MAIN RESULTS: As proof-of-concept, we developed an open-source neural recording
      device called NeRD. The NeRD prototype digitally transmits eight channels encoded
      at 10 kHz with 2 bits per sample. It occupies a volume of 2  *  2  *  2 cm3 and
      weighs 8 g with a small battery allowing for 2 h 40 min of autonomy. The power
      dissipation is 59.4 mW for a communication range of 8 m and transmission losses
      below 0.1%. The small weight and low power consumption offer the possibility of
      mounting the entire device on the head of a rodent without resorting to a
      separate head-stage and battery backpack. The NeRD prototype is validated in
      recording LFPs in freely moving rats at 2 bits per sample while maintaining an
      acceptable signal-to-noise ratio (>30 dB) over a range of noisy channels.
      SIGNIFICANCE: Adaptive quantization in neural implants allows for lower
      transmission bandwidths while retaining high signal fidelity and preserving
      fundamental frequencies in LFPs.

PMID- 29219120
TI  - Adsorption of H<sub>2</sub>, O<sub>2</sub>, H<sub>2</sub>O, OH and H on monolayer
      MoS<sub>2</sub>.
AB  - Hydrogen and hydrogen-containing gases are commonly used as reductants in
      chemical vapor deposition (CVD) growth of MoS<sub>2</sub>. Here, we consider the
      defects resulting from the presence of hydrogen during growth and the&#13;
      resulting electronically active defects. In particular, we find that the
      interstitial hydrogen defect is a&#13; negative-$U$ center with amphoteric donor
      and acceptor properties. Additionally, we consider the effects of the interaction
      with&#13; water and oxygen. The defects are analysed using density functional
      theory calculations.

PMID- 29219119
TI  - Density overwrites of internal tumor volumes in intensity modulated proton
      therapy plans for mobile lung tumors.
AB  - The purpose of this study was to investigate internal tumor volume density
      overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan
      degradation of mobile lung tumors. Four planning paradigms were compared for nine
      lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical
      target volume (ICTV) structures were defined encompassing their respective
      volumes in every 4DCT phase. The paradigms use different planning CT (pCT)
      created from the average intensity projection (AIP) of the 4DCT, overwriting the
      density within the IGTV to account for movement. The density overwrites were: (a)
      constant filling with 100 HU (C100) or (b) 50 HU (C50), (c) maximum intensity
      projection (MIP) across phases, and (d) water equivalent path length (WEPL)
      consideration from beam's-eye-view. Plans were created optimizing dose-influence
      matrices calculated with fast GPU Monte Carlo (MC) simulations in each pCT. Plans
      were evaluated with MC on the 4DCTs using a model of the beam delivery time
      structure. Dose accumulation was performed using deformable image registration.
      Interplay effect was addressed applying 10 times rescanning. Significantly less
      DVH metrics degradation occurred when using MIP and WEPL approaches. Target
      coverage ([Formula: see text] Gy(RBE)) was fulfilled in most cases with MIP and
      WEPL ([Formula: see text] Gy (RBE)), keeping dose heterogeneity low ([Formula:
      see text] Gy(RBE)). The mean lung dose was kept lowest by the WEPL strategy, as
      well as the maximum dose to organs at risk (OARs). The impact on dose levels in
      the heart, spinal cord and esophagus were patient specific. Overall, the WEPL
      strategy gives the best performance and should be preferred when using a 3D
      static geometry for lung cancer IMPT treatment planning. Newly available fast MC
      methods make it possible to handle long simulations based on 4D data sets to
      perform studies with high accuracy and efficiency, even prior to individual
      treatment planning.

PMID- 29219121
TI  - Magnetic and structural changes in
      LaCo<sub>0.9</sub>Mn<sub>0.1</sub>O<sub>3</sub> at high pressure.
AB  - The structural and magnetic properties of
      LaCo<sub>0.9</sub>Mn<sub>0.1</sub>O<sub>3</sub> have been studied as a function
      of pressure by neutron powder diffraction and DC magnetometry. The material is
      confirmed to exhibit rhombohedral R<sup>-</sup> 3c symmetry between ambient
      pressure and 6 GPa. We have determined the bulk modulus B<sub>0</sub> of the
      sample using a second-order Birch-Murnaghan equation of state which yielded:
      B<sub>0</sub>= 140(9) GPa and V<sub>0</sub> = 112.7(2)A<sup>3</sup>. We report a
      non-linear increase of the Curie temperature T<sub>c</sub> from an ambient
      pressure value of 224.7K to ~236 K at a pressure of 4 GPa. Finally, we confirm
      the glassy-like nature of the magnetism in
      LaCo<sub>0.9</sub>Mn<sub>0.1</sub>O<sub>3</sub>, which is maintained throughout
      the pressure range explored.

PMID- 29219122
TI  - Towards the use of breath for detecting mycobacterial infection: a case study in
      a murine model.
AB  - In the present research, the potential of breath analysis by comprehensive two
      dimensional gas chromatography coupled to mass spectrometry (GC*GC-MS) was
      investigated for the discrimination between healthy and infected mice. A pilot
      study employing a total of 16 animals was used to develop a method for breath
      analysis in a murine model for studying Mycobacterium tuberculosis complex (MTBC)
      using the M. bovis bacillus Calmette-Guerin. Breath was collected in Tedlar bags
      and concentrated onto thermal desorption tubes for subsequent analysis by GC*GC
      MS. Immunological test and bacterial cell count in bronchoalveolar lavage fluid
      and mice lung homogenate confirmed the presence of bacteria in the infected
      group. From the GC*GC-MS analysis, 23 molecules were found to mainly drive the
      separation between control and infected mice and their tentative identification
      is provided.This study shows that the overall used methodology is able to
      differentiate breath between healthy and infected animals, and the information
      herein can be used to further develop the mouse breath model to study MTBC
      pathogenesis, evaluate pre-clinical drug regimen efficacy, and to further develop
      the concept of breath-based diagnostics.

PMID- 29219123
TI  - Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat
      model.
AB  - OBJECTIVE: Numerous studies of vagal nerve stimulation (VNS) have been published
      showing it to be a potential treatment for chronic inflammation and other related
      diseases and disorders. Studies in recent years have shown that electrical
      stimulation of the vagal efferent fibers can artificially modulate cytokine
      levels and reduce systematic inflammation. Most VNS research in the treatment of
      inflammation have been acute studies on rodent subjects. Our study tested VNS on
      freely moving animals by stimulating and recording from the cervical vagus with
      nerve cuff electrodes over an extended period of time. APPROACH: We used methods
      of electrical stimulation, retrograde tracing (using Fluorogold) and post
      necropsy histological analysis of nerve tissue, flow cytometry to measure plasma
      cytokine levels, and MRI scanning of gastric emptying. This novel combination of
      methods allowed examination of physiological aspects of VNS previously
      unexplored. MAIN RESULTS: Through our study of 53 rat subjects, we found that
      chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold
      transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine
      levels and gastric emptying rates concurrently showed nominal differences between
      chronically cuffed rats and those tested with similar acute methods. Meanwhile,
      results of electrophysiological and histological tests of the cuffed nerves
      revealed them to be otherwise healthy, consistent with previous literature.
      SIGNIFICANCE: We hypothesize that due to these unforeseen and unexplored
      physiological consequences of the chronically cuffed vagus nerve in a rat, that
      inflammatory modulation and other vagal effects by VNS may become unreliable in
      chronic studies. Given our findings, we submit that it would benefit the VNS
      community to re-examine methods used in previous literature to verify the
      efficacy of the rat model for chronic VNS studies.

PMID- 29219124
TI  - 3D-printed adaptive acoustic lens as a disruptive technology for transcranial
      ultrasound therapy using single-element transducers.
AB  - The development of multi-element arrays for better control of the shape of
      ultrasonic beams has opened the way for focusing through highly aberrating media,
      such as the human skull. As a result, the use of brain therapy with transcranial
      focused ultrasound has rapidly grown. Although effective, such technology is
      expensive. We propose a disruptive, low-cost approach that consists of focusing a
      1 MHz ultrasound beam through a human skull with a single-element transducer
      coupled with a tailored silicone acoustic lens cast in a 3D-printed mold and
      designed using computed tomography-based numerical acoustic simulation. We
      demonstrate on N  =  3 human skulls that adding lens-based aberration correction
      to a single-element transducer increases the deposited energy on the target 10
      fold.

PMID- 29219125
TI  - Maternal mortality: An equity issue.

PMID- 29219126
TI  - Impact of nutritious meals on the nutritional status of the tribal students: A
      comparison between centralized kitchens (Annapurna) and regular kitchens in
      government tribal residential schools from two Districts of Maharashtra, India.
AB  - BACKGROUND: Tackling undernutrition is a global priority. It is the single
      largest risk factor influencing the burden of disease estimates at the global
      level. The Annapurna Project was undertaken by Government of Maharashtra to
      provide nutritious meals to Ashram/residential tribal school students through a
      centralized kitchen for achieving optimal growth and development and to prevent
      morbidity. OBJECTIVES: The primary objective of our work was to ascertain whether
      the provision of nutritious meals through centralized kitchens improves the
      proportion of underweight and stunted children. METHODS: We used a cluster trial
      with parallel intervention and control arms. The allocation ratio was 1:1 for
      participants in the intervention and control areas. The pilot was undertaken
      between 2015 and 2017. Tribal dominant Nashik and Palghar districts in
      Maharashtra were selected by the state government to implement the centralized
      kitchen plan. RESULTS: At the baseline, the percentage of underweight children in
      the intervention group was 36.9% and 31.9% in the control groups. The percentage
      of stunting in the intervention group was 30.0% and 38.2% in the control group.
      At the endline, 21.9% and 26.3% of the children were underweight. Both groups
      showed an improvement as compared to the baseline. However, the difference in
      reduction between the intervention and the control group was insignificant.
      Similarly, stunting also reduced to 12.9% and 14.6% in the intervention and
      control groups, respectively. CONCLUSION: The provision of regular nutritious
      meals, through centralized and local kitchen in government tribal residential
      schools of Maharashtra is effective and important in tackling undernutrition in
      Tribal children.

PMID- 29219127
TI  - Dengue fever in a municipality of West Bengal, India, 2015: An outbreak
      investigation.
AB  - BACKGROUND: In November 2015, death due to fever and increased number of fever
      cases were reported from Baranagar Municipality of North 24 Parganas district of
      West Bengal. OBJECTIVES: The episode was investigated with the objective to (1)
      confirm the existence of an outbreak, (2) describe it in terms of time, place,
      and person, (3) determine the cause of outbreak, and (4) recommend control
      measures. METHODS: Monthly incidence of dengue from 2012 to 2014 was calculated
      and compared with 2015 to confirm the outbreak. We used Integrated Disease
      Surveillance Programme definition and searched for suspect dengue cases going
      door-to-door in ward number one of Baranagar Municipality. Active case search was
      done in health facilities also. Information on date of onset, symptoms,
      sociodemographic, serological reports, and clinical outcome for suspected and
      confirmed dengue cases was collected. Blood specimens were collected for NS1
      ELISA/monoclonal IgM antibody capture-ELISA test. Environmental and entomological
      surveys were done. RESULTS: Six hundred and seventy-one dengue cases (Overall
      attack rate = 3/1000), two deaths (Case fatality = 3/1000) were reported during
      September 14, 2015, till December 12, 2015. Out of 34 wards, attack rate was
      highest in ward number 1 (0.7%) and was 3 per 1000 among females. All age groups
      were affected. Thirty-two percent required hospitalization. NS1 ELISA was
      positive for 612 cases. Out of interviewed 31 dengue cases, 94% had headache, 90%
      had myalgia, followed by arthralgia, rash, and retro-orbital pain. Only in ward
      number 1, house index was >5%. CONCLUSION: We confirmed dengue outbreak. All age
      groups got affected. Deaths occurred in this outbreak. Potential breeding sources
      were present in ward number 1.

PMID- 29219128
TI  - Economic burden of managing Type 2 diabetes mellitus: Analysis from a Teaching
      Hospital in Malaysia.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic disease that consumes a
      large amount of health-care resources. It is essential to estimate the cost of
      managing T2DM to the society, especially in developing countries. Economic
      studies of T2DM as a primary diagnosis would assist efficient health-care
      resource allocation for disease management. OBJECTIVE: This study aims to measure
      the economic burden of T2DM as the primary diagnosis for hospitalization from
      provider's perspective. METHODS: A retrospective prevalence-based costing study
      was conducted in a teaching hospital. Financial administrative data and inpatient
      medical records of patients with primary diagnosis (International Classification
      Disease-10 coding) E11 in the year 2013 were included in costing analysis.
      Average cost per episode of care and average cost per outpatient visit were
      calculated using gross direct costing allocation approach. RESULTS: Total
      admissions for T2DM as primary diagnosis in 2013 were 217 with total outpatient
      visits of 3214. Average cost per episode of care was RM 901.51 (US$ 286.20) and
      the average cost per outpatient visit was RM 641.02 (US$ 203.50) from provider's
      perspective. The annual economic burden of T2DM for hospitalized patients was RM
      195,627.67 (US$ 62,104) and RM 2,061,520.32 (US$ 654,450) for those being treated
      in the outpatient setting. CONCLUSIONS: Economic burden to provide T2DM care was
      higher in the outpatient setting due to the higher utilization of the health-care
      service in this setting. Thus, more focus toward improving T2DM outpatient
      service could mitigate further increase in health-care cost from this chronic
      disease.

PMID- 29219129
TI  - Utilization of safe drinking water and sanitary facilities in slum households of
      Siliguri, West Bengal.
AB  - BACKGROUND: With the rapid expansion of urban population, provision of safe water
      and basic sanitation is becoming a challenge; especially in slums. This is
      adversely affecting the health of the people living in such areas. OBJECTIVES:
      The study was conducted to measure the proportion of households using improved
      drinking water and sanitation facilities and to determine the association between
      diarrhea in under-five children with water and sanitation facilities. METHODS: A
      community-based, cross-sectional study was conducted among 796 slum households in
      Siliguri from January to March 2016 by interviewing one member from each
      household using a predesigned and pretested questionnaire based on the WHO/UNICEF
      Joint Monitoring Program Core questions on drinking water and sanitation for
      household surveys. RESULTS: A majority 733 (92.1%) of slum households used an
      improved drinking water source; 565 (71%) used public tap. About two-thirds
      (65.7%) household used improved sanitation facilities. About 15.8% households had
      reported diarrheal events in children in the previous month. Unimproved drinking
      water sources (AOR = 4.13; 1.91, 8.96), houses without piped water supply (AOR =
      4.43; 1.31, 15.00), and latrines located outside houses (AOR = 3.61; 1.44, 9.07)
      were significantly associated with the diarrheal events in children. CONCLUSION:
      The utilization of improved drinking water source was high but piped water
      connection and improved sanitary toilet used was low. Association between
      diarrheal events and type of drinking water sources and place of sanitation might
      suggest fecal contamination of water sources. Awareness generation through family
      centered educational programs could improve the situation.

PMID- 29219130
TI  - Effects of health education tool on select epidemiological factors associated
      with adult obese urban slum women.
AB  - BACKGROUND: National Family Health Survey-3 (2005-2006) India, found that 14.8%
      of Ever-Married Adults (age 15-49 years) had Body Mass Index (BMI) in the ranges
      of overweight and obese; compared to 10.6% in the National Family Health Survey
      2. These figures highlighted the fact that India already faces a dual burden of
      chronic malnutrition, i.e., obesity, besides undernutrition. Higher BMI,
      especially, increased abdominal fat is an important determinant of the
      development of diabetes. OBJECTIVE: This study aims to understand the effect of
      health education on obesity status of adult women above the age of 20 years in an
      urban slum area. METHODS: Community-based, interventional study, to assess select
      epidemiological factors associated with obesity-including measurement of
      anthropometry and assessing random blood sugar level; followed by an intervention
      (health education to only obese women by means of flip-chart); followed by a
      follow-up 6 months later. RESULTS: About 22.6% women were found to be obese.
      Almost, all dietary and physical activity parameters as well as weight improved
      for the better after the intervention, and the change was statistically
      significant. CONCLUSIONS: This community based interventional study was able to
      understand certain factors associated with pathophysiology of obesity in slum
      dwelling adult women, and effectively documented a reduction in weight along with
      a change in their obesogenic practices postintervention.

PMID- 29219131
TI  - Status of early childhood education under integrated child development services
      scheme in Bankura Municipality, West Bengal.
AB  - BACKGROUND: Early childhood education (ECE) is an important service provided by
      Integrated Child Development Services (ICDS). It is largely responsible for
      developing school readiness in children. OBJECTIVE: The objective of this study
      is to assess ECE component of ICDS services through measurement of school
      readiness and find out other correlates. METHODS: A cross-sectional evaluation
      study was carried out among Anganwadi centers (AWCs) under Bankura Municipality,
      West Bengal, India from July to November 2015. AWCs were selected by 30 cluster
      sampling. From each selected center Anganwadi worker (AWW), 7 randomly selected
      children of 5 years of age and their caregivers were included in the study. Data
      were collected by assessment of children, interview of AWWs and caregivers of
      children, observation of ECE activity and record review using ECE Program
      Evaluation Package developed by World Bank and predesigned schedule. Mean,
      standard deviation, proportions were estimated for description and correlation,
      unpaired t-test, analysis of one-way variance, multivariable linear regression
      were performed to find out correlates of school readiness using SPSS 22.0
      version. RESULTS: Average duration of ECE activity was 66.0 min/day which was far
      less than the norm. Overall average score of school readiness of 210 children was
      14.0 out of 40. Inadequate physical facility, poor classroom performance acted as
      deterrents for school readiness. Help in the study at home was revealed to be a
      determinant of school readiness. CONCLUSION: For the preparation of formal
      schooling of children most important needs of the hour are physical facility of
      AWCs, supportive supervision of AWWs, and creation of congenial environment at
      home.

PMID- 29219132
TI  - Assessment of the performance of community-directed treatment with ivermectin
      strategy for the control and elimination of onchocerciasis in Edo State, Nigeria.
AB  - BACKGROUND: Community-directed treatment with ivermectin (CDTI) was developed in
      the mid 1990's as a solution for the control and elimination of onchocerciasis.
      It requires that ivermectin be administered continuously over a period of at
      least 14 years with community involvement before elimination can be achieved.
      OBJECTIVES: The objective of this study is to assess the performance of CDTI
      strategy for control and elimination of onchocerciasis in endemic Local
      Government areas of Edo State. METHODS: A descriptive evaluation in a cross
      sectional, descriptive study design was conducted among 720 community members
      selected from six communities using multistage sampling technique, 11 Community
      directed distributors (CDDs), and 17 health workers involved in the
      implementation of the CDTI strategy in Edo State. Primary data were collected
      using an interviewer's administered questionnaire while secondary data were
      obtained from the State Ministry of Health. IBM SPSS version 21 software was used
      for data analysis. RESULTS: The highest therapeutic coverage (95.5%) was observed
      in Aden II community while the least therapeutic coverage (56.6%) was observed in
      Imeke community. Regarding the performance indicators, ivermectin supply, work of
      CDDs, training, monitoring and supervision, finances by communities had scores
      >=2.5 and were therefore considered as having satisfactory performance. However,
      community participation and ownership and health education and mobilization had
      scores <2.5 and as such considered as having unsatisfactory performance.
      CONCLUSION: Sustainability of the CDTI program in the study area is likely but
      not guaranteed as there is need for improvement in areas regarding community
      mobilization, participation, and ownership.

PMID- 29219133
TI  - Caregiver burden on wives of substance-dependent husbands and its correlates at a
      Tertiary Care Centre in Northern India.
AB  - BACKGROUND: Substance dependence is well recognized as a complex biopsychosocial
      phenomenon. Complications arising out of it not only impairs life of substance
      dependent patient but also causes enormous burden on their caregivers. Little
      attention has been paid to the relationship between caregiver burden and
      substance use. OBJECTIVES: The study was conducted to assess and compare the
      quantum of burden on wives of alcohol and heroin-dependent patients and also to
      determine the correlation between sociodemographic factors and caregiver burden.
      METHODS: A cross-sectional study was conducted at a tertiary care center of North
      India to compare burden on wives of alcohol and heroin dependent husbands. Burden
      was assessed using burden assessment schedule (Sell et al.). Data obtained were
      analyzed using SPSS software. RESULTS: Wives of both alcohol and heroin dependent
      patients had moderate-to-high burden of caregiving (Score of 38.1 out of maximum
      60), those of heroin dependent patients perceived more burden in the factors of
      "impact on marital relationship," "appreciation of caregiving," "impact on
      relation with others," and overall burden as compared to wives of alcohol
      dependent patients. Significant negative correlation was found between "impact on
      marital relationship," "appreciation of caregiving," and "impact on relation with
      others" scores and patients' education status as well as between "appreciation of
      caregiving" score and wives' age where higher score denotes more burden.
      CONCLUSION: Significant burden exists on wives of substance-dependent patients;
      thus management plans must be devised aiming not only patients but also wives so
      as to reduce burden.

PMID- 29219134
TI  - Does infant feeding method influence the incidence and pattern of morbidities
      among human immunodeficiency virus-exposed uninfected nigerian infants?
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-exposed infants enrolled into the
      prevention of mother-to-child transmission of HIV program generally receive
      antiretroviral therapy (ARV), but the feeding methods differ based on several
      socioeconomic and cultural differences. OBJECTIVE: The objective of the study was
      to examine the incidence and pattern of morbidities among HIV-exposed uninfected
      (HEU) Nigerian infants and determine any relationship with infant feeding
      methods. METHODS: A review of the hospital records of all HEU infants attending
      the Virology Clinic of Olabisi Onabanjo University Teaching Hospital, Sagamu,
      Nigeria, between July 2013 and June 2015, was done. The recorded data included
      biodemographic profile, social parameters, feeding methods, anthropometry, and
      morbidities. The feeding method groups were statistically compared in relation to
      the various morbidities. RESULTS: Out of 119 children, 81.5% were exclusively
      breastfed, whereas 18.5% had exclusive breast milk substitute feeding. About half
      had various morbidities which included upper airway infections (UAIs) (16.8%),
      malaria (15.9%), malnutrition (8.4%), diarrhea (8.4%), and pneumonia (2.5%). The
      frequencies of these conditions were similar among infant groups irrespective of
      feeding method. The infants with and without morbidities were comparable in terms
      of the frequency of exclusive breastfeeding (80.3% vs. 82.8%). Low family
      socioeconomic status (SES) (odds ratio [OR] = 7.7) and ARV use (OR = 0.4) among
      infants were predictors of morbidities among HEU infants. CONCLUSION: The
      incidence and pattern of morbidities among HEU infants showed no relation to the
      mode of feeding. Rather, family SES and the use of antiretroviral drugs were
      predictors of morbidities among HEU infants.

PMID- 29219135
TI  - Waiting time of inpatients before elective surgical procedures at a State
      Government Teaching Hospital in India.
AB  - BACKGROUND: Abundant published literature exists addressing the issues of
      outpatient waiting lists before surgery. However, there is no published
      literature on inpatient waiting time before elective surgical procedures.
      OBJECTIVES: This study aims to measure the inpatient waiting time, identify the
      factors that affect the inpatient waiting time, and recommend the ways of
      reducing the waiting time of inpatients before elective surgical procedures, at a
      state government teaching hospital in India. METHODS: Descriptive research
      methods and quality control tools were used for this prospective observational
      study. Descriptive statistics, Shapiro-Wilk test of normality, Wilcoxon-Mann
      Whitney Test, and Kruskal-Wallis test were used. Pareto charts were used to
      highlight the most important modifiable factors among the set of factors causing
      increased waiting time. We also applied the M/M/c model (Erlang - A model) of
      queue theory to analyze the traffic intensity and system congestion. RESULTS: The
      median waiting time of inpatients before elective surgery was 12 days
      (interquartile range = 11.5 days). The waiting time was influenced significantly
      (P < 0.05) by the patient's age, physical status, and the financial status. The
      surgical specialty, blood product booking and procurement, cross-specialty
      consultation before surgery, and Intensive Care Unit booking were the other
      important factors. CONCLUSION: Modifiable and nonmodifiable factors affecting the
      inpatient waiting time of surgical patients were identified. Control measures
      that can reduce the waiting time of inpatients before elective surgery were
      identified.

PMID- 29219136
TI  - Assessment of village health sanitation and nutrition committees of Chandigarh,
      India.
AB  - BACKGROUND: Village Health, Sanitation and Nutrition Committees (VHSNCs), one of
      the key interventions introduced by National Rural Health Mission, are an
      important mechanism to ensure community participation and ownership for
      decentralized health planning. OBJECTIVES: To assess the implementation status of
      VHSNCs and analyze the issues regarding their implementation in the villages of
      Chandigarh. METHODS: A cross-sectional mix method study was conducted in the year
      2015 in all 22 VHSNCs of Chandigarh. The data of VHSNCs' members were obtained
      using interview schedule and in-depth interview checklist, while record review
      checklist was used to assess functioning of VHSNCs. A scoring sheet was developed
      based on sociodemographic profile, public services monitoring, training status,
      untied funds utilization, and regularity of monthly meetings. The comparison of
      VHSNC indicators was done between villages under Panchayat and Municipal
      Corporation (MC). RESULTS: Most VHSNCs' members are trained (except medical
      officers) and had their joint bank account (95.4%). Maximum fund is utilized for
      administrative purposes, leaving less for health and nutrition-related
      activities. Most villages (68.9%) got 25-30 score depicting that implementation
      status of VHSNCs under these villages is "promising," while one and six villages
      were "low performing" and "good performing," respectively. Public service
      monitoring indicator's implementation was better in villages under Panchayat as
      compared to those under MC. CONCLUSION: The performance of most villages having
      VHSNCs under Chandigarh was satisfactory. Few areas such as training of medical
      officers and supportive supervision of VHSNCs needs strengthening for achieving
      mandate of National Rural Health Mission regarding community ownership and
      decentralizing health sector.

PMID- 29219137
TI  - Bridging miles to achieve milestones: Corporate social responsibility for primary
      health care.
AB  - Sustainable Developmental Goals aim to provide "Good health for all". The task
      though immense ,requires equitable and efficient distribution of health resources
      to the community, reached predominantly by the Primary Health Centres.
      Strengthening these centres is essential to attain the goal. Adequate health
      financing is one of the important determinants for utilizing the optimal
      potential of these centres . Pooling funds from alternate financing strategies as
      Corporate Social Responsibility (CSR) funds may give impetus and facilitate
      healthcare affordability to the underserved population. This convergence of
      vision of corporate funding for "basic health services" may bridge the gap
      arising out of inadequate funding and facilitate "Good Health for all" in India.

PMID- 29219138
TI  - Organ donation in India: Scarcity in abundance.
AB  - In modern era, India witnessed its first successful corneal, kidney and cardiac
      transplant in the year 1960, 1967 and 1994 though the reverberations for organ
      donation and transplantation (ODT) existed since time-memorial with roots
      existing in Hindu mythology along with vivid example of Guru Dadheech and lord
      Ganesha. No country in the world is able to meets its organ requirement.
      Government of India promulgated Transplantation of Human Organ and Tissues Act in
      1994 and with the view to enlarge its scope and promote organ donation government
      has brought new amendments as of year 2014 and 2017. In the background of this
      journey many new developmental milestones have been achieved in the country
      however organ donation which has assumed public health significance has been
      consistently lower than expectations. This manuscript highlights the current
      status of ODT in the country; legislative environment, limitations, challenges,
      health education activities, and newer initiatives.

PMID- 29219139
TI  - A point source outbreak of acute gastroenteritis among school students in Kerala,
      India.
AB  - An outbreak investigation was initiated following an outbreak of acute
      gastroenteritis among schoolchildren in Kottarakara. Steps included active search
      for cases at schools, describing the outbreak in terms of person, place, and
      time, generating hypothesis based on the findings from descriptive study,
      environmental observations, and testing the hypothesis using a case-control
      design. The final line list consisted of 871 children from different schools who
      attended a Republic Day parade. Having consumed the lemon juice near railway
      station (odds ratio [OR] 29.14; 95% confidence interval CI 9.06-93.67) during
      Republic day parade was associated with the outbreak. The time frame of the
      disease occurrence, laboratory results, and the results of the analytical study
      indicated the point source of acute gastroenteritis outbreak as the contaminated
      water used for lemon juice distributed during the parade. The findings warrant
      effective food and water safety surveillance, especially during mass gatherings.

PMID- 29219140
TI  - "Near-Miss" Obstetric events and maternal mortality in a Tertiary Care Hospital.
AB  - Obstetric near-miss or severe acute maternal morbidity is gaining interest
      internationally as a new indicator of the quality of obstetric care. This is a
      retrospective study conducted using "The WHO Near-Miss Approach" to provide
      insight into obstetric emergencies, near-miss cases, and maternal deaths in our
      hospital. The maternal near-miss ratio was 8.4/1000 live births, maternal near
      miss to mortality ratio was 5.3:1. Hemorrhage was the leading cause (43.7%) of
      morbidity in near-miss cases while hypertensive disorders were the leading cause
      in maternal deaths (66.6%). Among women with potentially life-threatening
      conditions, severe preeclampsia was the most common complication (50.54%). The
      near-miss approach helps to evaluate and improve the quality of care provided by
      health system by identifying the pattern of severe maternal morbidity and
      mortality, strengths and weakness in the referral system and the clinical
      interventions available and the ways in which improvements can be made.

PMID- 29219141
TI  - Biochemical iodine deficiency in selected schools of aligarh.
AB  - The goiter prevalence reflects the iodine deficiency in past while urinary iodine
      excretion levels (UIEL) gives the current status of iodine nutrition. The study
      was conducted to assess the status of biochemical iodine deficiency in school
      children of 1st-5th standard (6-12 years). A total of 907 students of seven
      schools were included using probability proportional to size method. About 10% of
      urine samples from total children were tested for UIEL. Statistical analysis was
      done using SPSS version 20 (IBM SPSS Statistics for Windows, Version 20.0.
      Armonk, NY: IBM Corp). UIEL values lower than 100 MUg/L were observed in 23.3% of
      samples. The proportion of children with UIEL of <20 MUg/L was nil in 6 years.
      Out of 13 students who were consuming salt with nil iodine content, 46.2% had <20
      MUg/L UIEL. The prevalence of iodine deficiency, calculated by the proportion of
      children having UIEL of <100 MUg/L, was 23.3%. Based on UIEL values, the area
      would be categorized as having "no biochemical iodine deficiency."

PMID- 29219143
TI  - The utility of gamification in public health.

PMID- 29219142
TI  - Inappropriate classification of body mass index of adolescent girls under SABLA
      scheme.

PMID- 29219144
TI  - Apical pseudoaneurysm after transapical transcatheter aortic valve implantation.

PMID- 29219146
TI  - New traffic light on Th17 Avenue.
AB  - Activation of STAT3-coupled receptors along with TGF-beta signaling are
      fundamental for Th17 cell differentiation both in vivo and in vitro. A recent
      paper shows that TGF-beta signaling relieves SKI-mediated transcriptional
      repression of Rorc, the key regulator of the Th17 program.

PMID- 29219148
TI  - Obesity: Sex differences in insulin resistance.

PMID- 29219150
TI  - Diabetes: ANGPTL8 as an early predictor of gestational diabetes mellitus.

PMID- 29219151
TI  - Familial hypercholesterolaemia.
AB  - Familial hypercholesterolaemia is a common inherited disorder characterized by
      abnormally elevated serum levels of low-density lipoprotein (LDL) cholesterol
      from birth, which in time can lead to cardiovascular disease (CVD). Most cases
      are caused by autosomal dominant mutations in LDLR, which encodes the LDL
      receptor, although mutations in other genes coding for proteins involved in
      cholesterol metabolism or LDLR function and processing, such as APOB and PCSK9,
      can also be causative, although less frequently. Several sets of diagnostic
      criteria for familial hypercholesterolaemia are available; common diagnostic
      features are an elevated LDL cholesterol level and a family history of
      hypercholesterolaemia or (premature) CVD. DNA-based methods to identify the
      underlying genetic defect are desirable but not essential for diagnosis. Cascade
      screening can contribute to early diagnosis of the disease in family members of
      an affected individual, which is crucial because familial hypercholesterolaemia
      can be asymptomatic for decades. Clinical severity depends on the nature of the
      gene that harbours the causative mutation, among other factors, and is further
      modulated by the type of mutation. Lifelong LDL cholesterol-lowering treatment
      substantially improves CVD-free survival and longevity. Statins are the first
      line therapy, but additional drugs, such as ezetimibe, bile acid sequestrants,
      PCSK9 inhibitors and other emerging therapies, are often required.

PMID- 29219149
TI  - Global aetiology and epidemiology of type 2 diabetes mellitus and its
      complications.
AB  - Globally, the number of people with diabetes mellitus has quadrupled in the past
      three decades, and diabetes mellitus is the ninth major cause of death. About 1
      in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2
      diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM
      global epidemic, with China and India the top two epicentres. Although genetic
      predisposition partly determines individual susceptibility to T2DM, an unhealthy
      diet and a sedentary lifestyle are important drivers of the current global
      epidemic; early developmental factors (such as intrauterine exposures) also have
      a role in susceptibility to T2DM later in life. Many cases of T2DM could be
      prevented with lifestyle changes, including maintaining a healthy body weight,
      consuming a healthy diet, staying physically active, not smoking and drinking
      alcohol in moderation. Most patients with T2DM have at least one complication,
      and cardiovascular complications are the leading cause of morbidity and mortality
      in these patients. This Review provides an updated view of the global
      epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for
      T2DM and its complications.

PMID- 29219152
TI  - Corrigendum: BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression
      by Down-Regulation of 5-HT3 Receptors.
AB  - [This corrects the article on p. 306 in vol. 11, PMID: 29075179.].

PMID- 29219147
TI  - Mitochondrial metabolism and cancer.
AB  - Glycolysis has long been considered as the major metabolic process for energy
      production and anabolic growth in cancer cells. Although such a view has been
      instrumental for the development of powerful imaging tools that are still used in
      the clinics, it is now clear that mitochondria play a key role in oncogenesis.
      Besides exerting central bioenergetic functions, mitochondria provide indeed
      building blocks for tumor anabolism, control redox and calcium homeostasis,
      participate in transcriptional regulation, and govern cell death. Thus,
      mitochondria constitute promising targets for the development of novel anticancer
      agents. However, tumors arise, progress, and respond to therapy in the context of
      an intimate crosstalk with the host immune system, and many immunological
      functions rely on intact mitochondrial metabolism. Here, we review the cancer
      cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence
      all steps of oncogenesis, with a focus on the therapeutic potential of targeting
      mitochondrial metabolism for cancer therapy.

PMID- 29219153
TI  - Corrigendum: Different Neural Correlates of Emotion-Label Words and Emotion-Laden
      Words: An ERP Study.
AB  - [This corrects the article on p. 455 in vol. 11, PMID: 28983242.].

PMID- 29219154
TI  - Developing nanotube junctions with arbitrary specifications.
AB  - Experimentally synthesized carbon nanotube (CNTs) junctions (either single or
      with 2D/3D CNT network topology) are expected to have random orientation of
      defect sites (non-hexagonal rings) around the junction. This random and irregular
      nature of the junction topology and defect characteristics is expected to affect
      their strength and durability as well as impact the associated mesoscopic and
      macroscopic properties. On the contrary, theoretical and computational studies
      often investigate structure-property relationships of pristine and regular
      junctions of carbon nanostructures. In this study, we developed a computational
      framework to model a variety of junction structures between CNTs with arbitrary
      spatial (orientation and degree of overlap) and intrinsic (chirality)
      specifications. The developed computational model also has the ability to tune
      the degree of topological defects around the junction via a variety of defect
      annihilation approaches. Our method makes use of the primal/dual meshing concept,
      where the development and manipulation of the junction nodes occur using
      triangular meshes (primal mesh), which is eventually converted to its dual mesh
      (honeycomb mesh) to render a fully covalently bonded CNT junction. Here each
      carbon atom has 3 bonded neighbors (mimicking sp2 hybridization). Under a given
      set of CNT orientation, overlap and chirality specifications, the approach
      creates a number of CNT junction configurations with varying degrees of energetic
      stability, offering an opportunity to investigate the effect of topological
      arrangement of defects around the junction on mechanical, electrical and thermal
      properties. In addition, it is shown via few examples that the discussed
      methodology can easily be extended to create multi-junction nanotube clusters,
      multi-wall nanotube junctions, as well as true 3D random network structures.

PMID- 29219155
TI  - Mechanochemical synthesis of cooperative spin crossover materials.
AB  - We describe the synthesis of switchable spin crossover materials via
      mechanochemistry for the first time. Three chemically diverse spin crossover
      materials have been produced using solvent-free grinding. Crucially, cooperative
      spin transition behavior and crystallinity is retained, presenting exciting
      opportunities for the discovery of new materials with switchable magnetic,
      optical and structural properties.

PMID- 29219156
TI  - Research into food portion size: methodological aspects and applications.
AB  - Portion sizes for certain foods have been increasing dramatically in recent years
      alongside obesity rates, concurring with the phenomenon of the portion size
      effect (more is consumed when more is offered). Portion size may be defined based
      on different purposes such as for dietary assessment, or therapeutic advice or
      food labelling, resulting in a variety of measurement methods and specifications.
      This situation has resulted in disagreements on establishing portion size
      recommendations by manufacturers, food distributors, restaurants, health
      professionals and policy makers, contributing to confusion amongst consumers on
      the amounts of food to be consumed, and potentially increasing the likelihood of
      overeating and other obesity-related behaviours. Such variability is also
      reflected in the research field making comparison across studies on portion size
      difficult. The aim of this review is to provide an overview of definitions and
      methods used in research to evaluate portion-size related outcomes, including
      methods to estimate amounts consumed by individuals as part of dietary
      assessment; methods to analyse cognitive mechanisms related to portion size
      behaviour; and methods to evaluate the impact of portion size manipulations as
      well as individual plus environmental factors on portion size behaviour. Special
      attention has been paid to behavioural studies exploring portion size cognitive
      processes given the lack of previous methodological reviews in this area. This
      information may help researchers, clinicians and other stakeholders to establish
      clearer definitions of portion size in their respective areas of work and to
      standardise methods to analyse portion size effects.

PMID- 29219157
TI  - Protein networks in the maturation of human iron-sulfur proteins.
AB  - The biogenesis of iron-sulfur (Fe-S) proteins in humans is a multistage process
      occurring in different cellular compartments. The mitochondrial iron-sulfur
      cluster (ISC) assembly machinery composed of at least 17 proteins assembles
      mitochondrial Fe-S proteins. A cytosolic iron-sulfur assembly (CIA) machinery
      composed of at least 13 proteins has been more recently identified and shown to
      be responsible for the Fe-S cluster incorporation into cytosolic and nuclear Fe-S
      proteins. Cytosolic and nuclear Fe-S protein maturation requires not only the CIA
      machinery, but also the components of the mitochondrial ISC assembly machinery.
      An ISC export machinery, composed of a protein transporter located in the
      mitochondrial inner membrane, has been proposed to act in mediating the export
      process of a still unknown component that is required for the CIA machinery.
      Several functional and molecular aspects of the protein networks operative in the
      three machineries are still largely obscure. This Review focuses on the Fe-S
      protein maturation processes in humans with the specific aim of providing a
      molecular picture of the currently known protein-protein interaction networks.
      The human ISC and CIA machineries are presented, and the ISC export machinery is
      discussed with respect to possible molecules being the substrates of the
      mitochondrial protein transporter.

PMID- 29219158
TI  - Electroanalytical study of dopamine oxidation on carbon electrodes: from the
      macro- to the micro-scale.
AB  - The oxidation of dopamine in strongly acidic (pH = 0) solution is investigated
      using microdisc, microcylinder and macro-electrodes together with a range of
      voltage scan rates. Kinetic and mechanistic analysis over the full range of mass
      transport conditions show a behaviour consistent with an ECE process with a fast
      chemical step and in which the second electron transfer is thermodynamically more
      favourable than the first step. Accordingly the reaction effectively behaves as
      an EE process.

PMID- 29219159
TI  - Coupling interconnected MoO3/WO3 nanosheets with a graphene framework as a highly
      efficient anode for lithium-ion batteries.
AB  - A rationally assembled three-dimensional graphene framework coupled with
      interconnected molybdenum/tungsten oxide nanosheets (MoO3/WO3-GF) has been
      developed via a one-step template-free strategy. With the unique nanostructure,
      the obtained anode material not only exhibits a high reversible capacity of about
      1000 mA h g-1, approaching the theoretical capacity of MoO3 and WO3 materials,
      but also shows excellent rate capability and cycling performance with negligible
      capacity attenuation after a long-time test. These features make it a promising
      candidate material for high-performance commercial lithium-ion batteries in the
      future.

PMID- 29219160
TI  - Rainbows, supernumerary rainbows and interference effects in the angular
      scattering of chemical reactions: an investigation using Heisenberg's S matrix
      programme.
AB  - In earlier research, we have demonstrated that broad "hidden" rainbows can occur
      in the product differential cross sections (DCSs) of state-to-state chemical
      reactions. Here we ask the question: can pronounced and localized rainbows,
      rather than broad hidden ones, occur in reactive DCSs? Further motivation comes
      from recent measurements by H. Pan and K. Liu, J. Phys. Chem. A, 2016, 120, 6712,
      of a "bulge" in a reactive DCS, which they conjecture is a rainbow. Our
      theoretical approach uses a "weak" version of Heisenberg's scattering matrix
      program (wHSMP) introduced by X. Shan and J. N. L. Connor, Phys. Chem. Chem.
      Phys., 2011, 13, 8392. This wHSMP uses four general physical principles for
      chemical reactions to suggest simple parameterized forms for the S matrix; it
      does not employ a potential energy surface. We use a parameterization in which
      the modulus of the S matrix is a smooth-step function of the total angular
      momentum quantum number, J, and (importantly) its phase is a cubic polynomial in
      J. We demonstrate for a Legendre partial wave series (PWS) the existence of
      pronounced rainbows, supernumerary rainbows, and other interference effects, in
      reactive DCSs. We find that reactive rainbows can be more complicated in their
      structure than the familiar rainbows of elastic scattering. We also analyse the
      angular scattering using Nearside-Farside (NF) PWS theory and NF PWS Local
      Angular Momentum (LAM) theory, including resummations of the PWS. In addition, we
      apply full and NF asymptotic (semiclassical) rainbow theories to the PWS - in
      particular, the uniform Airy and transitional Airy approximations for the farside
      scattering. This lets us prove that structure in the DCSs are indeed rainbows,
      supernumerary rainbows as well as other interference effects.

PMID- 29219161
TI  - The atomic level mechanism of white phosphorous demolition by di-iodine.
AB  - A detailed mechanism of the I2-induced transformation of white phosphorus into
      PI3 emerges from a DFT analysis. This multi-step process implies that at any
      stage one P-P and two I-I bonds cleavages, associated with the formation of two P
      I bonds plus an in situ generated brand new I2 molecule. Significant electron
      transfer between the atoms is observed at any step, but the reactions are better
      defined as concerted rather than redox. Along the steepest descent to the
      product, no significant barrier is encountered except for the very first P4
      activation, which costs +14.6 kcal mol-1. At the atomic level, one first I2
      molecule, a typical mild oxidant, is first involved in a linear halogen bonding
      interaction (XB) with one P donor, while its terminal I atom is engaged in an
      additional XB adduct with a second I2. Significant electron transfer through the
      combined diatomics allows the external I atom of the dangling I3 grouping to
      convey electrons into the sigma* level of one P-P bond with its consequent
      cleavage. This implies at some point the appearance of a six-membered ring, which
      alternatively switches its bonding and no-bonding interactions. The final
      transformation of the P2I4 diphosphine into two PI3 phosphines is enlightening
      also for the specific role of the I substituents. In fact, it is proved that an
      organo-diphosphine analogue hardly undergoes the separation of two phosphines, as
      reported in the literature. This is attributable to the particularly high donor
      power of the carbo-substituted P atoms, which prevents the concertedness of the
      reaction but favors charge separation in an unreactive ion pair.

PMID- 29219162
TI  - Structural diversity in the alkaline earth metal compounds of tetra and
      pentacyanocyclopentadienide.
AB  - The reaction of the alkaline earth dihalides MCl2.nH2O (M = Mg, Ca, Sr, Ba) with
      the silver salts of cyanocyclopentadienides [C5(CN)4X]- (X = H, CN) yields the
      corresponding alkaline earth biscyclopentadienides. The
      pentacyanocyclopentadienides of Mg and Ca and the tetracyanocyclopentadienides of
      Ca, Sr and Ba were studied by X-ray diffraction. The Mg compound 1a' shows only
      coordination by water molecules, but numerous hydrogen bridges between
      coordinated water molecules and pentacyanocyclopentadienide anions and further
      guest water molecules create a three-dimensional network. The structure of the
      calcium pentacyanocyclopentadienide 1b shows two inequivalent anions, one
      uncoordinated and one coordinating via three nitrile groups to three different
      metal ions. Ca2+ and [C5(CN)5]- ions together form a rhombohedral grid structure,
      in which the voids are filled by the uncoordinated [C5(CN)5]- ion and guest water
      molecules, all taking part in a hydrogen bond network too. The isostructural Ca
      and Sr tetracyanocyclopentadienides exhibit eightfold coordinated metal ions, in
      which both [C5(CN)4H]- anions coordinate to the metals by one cyano group each,
      and each anion bridging two metal ions. Thus, one-dimensional ribbons of
      {Ca[C5(CN)4H]4/2}x are formed, which are interconnected via hydrogen bridges from
      and to coordinated water molecules to build a three-dimensional network. The
      barium tetracyanocyclopentadienide contains a ninefold coordinated metal with the
      anion using three of its nitrile functions for coordination to three different
      metals. A complicated network is formed by four interpenetrating {Ba[C5(CN)4H]2}
      helices that are interconnected via the remaining third nitrile function, while
      the fourth nitrile group always remains uncoordinated. Although all coordinated
      water molecules are involved in hydrogen bridges, these are not contributing to
      the formation of the network.

PMID- 29219163
TI  - Lessons to Be Learned about Clinical Trials in Preclinical AD from Ongoing
      Longitudinal Studies.

PMID- 29219164
TI  - Drug Development in AD: Point of View from the Industry.

PMID- 29219165
TI  - Impact of Dietary Factors and Inflammation on Cognition among Older Adults.
AB  - OBJECTIVE: This study examined the influence of age, nutrition (as measured
      through food diaries and serum/plasma biomarkers) and inflammatory markers on
      cognitive performance in adults 60 years of age and older. DESIGN: A cross
      sectional population based study, data from the National Health and Nutrition
      Examination Survey (NHANES; 2001-2002 wave). PARTICIPANTS: This study included
      1,048 adults who had valid dietary data, blood biomarkers, were 60 years or
      older, completed the cognitive test, and had complete demographic information.
      METHOD: A series of regression models were used to examine the relationship
      between cognitive function as measured by the Digit Symbol Substitution Task
      (DSST), dietary factors/biomarkers and inflammation. Mediation analyses were then
      utilized to examine whether individual nutrients accounted for the relationships
      between age and DSST performance. RESULTS: Dietary fat intake, serum vitamin E,
      serum folate, serum iron, plasma homocysteine, and serum vitamin D were
      significantly associated with better DSST performance. Elevated fibrinogen and C
      reactive protein, were significantly associated with poorer cognitive function,
      but did not remain statistically significant after controlling for age, gender,
      education, ethnicity, income, and total calorie intake. Serum vitamin D and
      plasma homocysteine accounted for a portion of age-related variance in DSST.
      Specifically, higher levels of vitamin D were related to better DSST performance,
      while higher homocysteine resulted in poorer cognitive performance. CONCLUSION:
      Diet and nutrition are important modifiable factors that can influence health
      outcomes and may be beneficial to remediate age-related declines in cognition.
      Adequate nutrition may provide a primary preventive approach to healthy aging and
      maintenance of cognitive functioning in older adults.

PMID- 29219166
TI  - Muslim gay men: identity conflict and politics in a Muslim majority nation.
AB  - While a number of investigations have examined how gay Muslim men view
      homosexuality in relation to religious Western homophobia, this research
      constitutes the first account of the experiences of self-identified gay men
      living in an African, Muslim nation, where same-sex sex is both illegal and
      actively persecuted. We interviewed 28 gay men living in Tunisia in order to
      understand how they assimilate their sexual, religious and ethnic identities
      within a highly homophobic culture. Utilizing notions of homoerasure and
      homohysteria (McCormack and Eric Anderson ,b), and examining the intersection of
      identity conflict and new social movement theory, we highlight four strategies
      that participants use to negotiate the dissonance of living with conflicting
      identities in a context of religious homophobia: (1) privileging their Islamic
      identities and rejecting homosexuality as a legitimate sexual identity; (2)
      rejecting Islam and accepting homosexuality as a legitimate sexual identity; (3)
      interpreting Islam to be supportive of homosexuality; and (4) creating a non
      penetrative homosexuality to be compatible with literal Qur'anic interpretations.
      We discuss the multiple difficulties these men face in relation to religious
      intolerance and ethnic heteronormativity, and reflect upon the possibilities and
      obstacles of using Western identity politics towards the promotion of social
      justice within a framework of growing homohysteria.

PMID- 29219167
TI  - Quantitative Understanding of QTc Prolongation and Gender as Risk Factors for
      Torsade de Pointes.
AB  - Several risk factors for development of a potentially fatal ventricular
      arrhythmia, torsade de pointes, have been observed, including female gender.
      However, in most investigations, only few torsade events were included and/or
      rarely were postdose heart rate corrected QT (QTc) measurements included, as a
      surrogate of drug exposure. We developed a multivariate logistic regression model
      using data from 22,214 patients (33% women) with 84 torsade events (56% women) to
      evaluate the relationship between risk factors for torsade using data from four
      anti-arrhythmic drug development programs. Before model development, we evaluated
      different QT/QTc postdose metrics (average, maximum, etc.) to determine which QT
      metric should be included into the model. The developed multivariate model showed
      that, after accounting for known risk factors for torsade and postdose QTc, that
      female gender remained a significant risk factor for torsade.

PMID- 29219168
TI  - Between evidence and commerce - the case of sufentanil sublingual tablet systems.

PMID- 29219169
TI  - Pharmacokinetics and pharmacodynamics of sublingual sufentanil for postoperative
      pain management.
AB  - Achieving successful treatment of postoperative pain remains a challenge.
      Recently, a sufentanil sublingual tablet system has been developed for treatment
      of moderate-to-severe postoperative pain. The phenylpiperidine sufentanil is a
      potent analgesic that rapidly crosses the blood-brain barrier and selectively
      activates central MU-opioid receptors. The system makes use of a hand-held
      dispenser system, which contains forty 15-MUg sufentanil sublingual micro
      tablets. The patient can release one tablet at 20-min intervals using a unique
      radiofrequency adhesive tag, which is wrapped around the patient's thumb. In this
      review, the authors discuss the pharmacology of sublingual sufentanil with
      reference to its suitability in the treatment of postoperative pain, the current
      evidence for the sublingual sufentanil system in postoperative pain treatment,
      and advantages and limitations of the sublingual system. We conclude that
      sufentanil is suited for the transmucosal route due to its pharmacokinetic
      profile, including rapid onset, absence of active metabolites and low tissue
      accumulation. The efficacy and safety of the sufentanil sublingual tablet system
      has been shown in over 600 patients in a limited set of studies; further
      independent studies are required to determine the position of the system among
      other forms of postoperative pain treatment. We conclude that the sublingual
      sufentanil tablet system allows effective pain relief, and allows patients to
      control their own pain relief and early postoperative mobility.

PMID- 29219170
TI  - Learning to Individuate: The Specificity of Labels Differentially Impacts Infant
      Visual Attention.
AB  - This study examined differences in visual attention as a function of label
      learning from 6 to 9 months of age. Before and after 3 months of parent-directed
      storybook training with computer-generated novel objects, event-related
      potentials and visual fixations were recorded while infants viewed trained and
      untrained images (n = 23). Relative to a pretraining, a no-training control group
      (n = 11), and to infants trained with category-level labels (e.g., all labeled
      "Hitchel"), infants trained with individual-level labels (e.g., "Boris," "Jamar")
      displayed increased visual attention and neural differentiation of objects after
      training.

PMID- 29219171
TI  - Benzodiazepines for psychosis-induced aggression or agitation.
AB  - BACKGROUND: Acute psychotic illness, especially when associated with agitated or
      violent behaviour, can require urgent pharmacological tranquillisation or
      sedation. In several countries, clinicians often use benzodiazepines (either
      alone or in combination with antipsychotics) for this outcome. OBJECTIVES: To
      examine whether benzodiazepines, alone or in combination with other
      pharmacological agents, is an effective treatment for psychosis-induced
      aggression or agitation when compared with placebo, other pharmacological agents
      (alone or in combination) or non-pharmacological approaches. SEARCH METHODS: We
      searched the Cochrane Schizophrenia Group's register (January 2012, 20 August
      2015 and 3 August 2016), inspected reference lists of included and excluded
      studies, and contacted authors of relevant studies. SELECTION CRITERIA: We
      included all randomised controlled trials (RCTs) comparing benzodiazepines alone
      or in combination with any antipsychotics, versus antipsychotics alone or in
      combination with any other antipsychotics, benzodiazepines or antihistamines, for
      people who were aggressive or agitated due to psychosis. DATA COLLECTION AND
      ANALYSIS: We reliably selected studies, quality assessed them and extracted data.
      For binary outcomes, we calculated standard estimates of risk ratio (RR) and
      their 95% confidence intervals (CI) using a fixed-effect model. For continuous
      outcomes, we calculated the mean difference (MD) between groups. If there was
      heterogeneity, this was explored using a random-effects model. We assessed risk
      of bias and created a 'Summary of findings' table using GRADE. MAIN RESULTS:
      Twenty trials including 695 participants are now included in the review. The
      trials compared benzodiazepines or benzodiazepines plus an antipsychotic with
      placebo, antipsychotics, antihistamines, or a combination of these. The quality
      of evidence for the main outcomes was low or very low due to very small sample
      size of included studies and serious risk of bias (randomisation, allocation
      concealment and blinding were not well conducted in the included trials, 30% of
      trials (six out of 20) were supported by pharmaceutical institutes). There was no
      clear effect for most outcomes.Benzodiazepines versus placeboOne trial compared
      benzodiazepines with placebo. There was no difference in the number of
      participants sedated at 24 hours (very low quality evidence). However, for the
      outcome of global state, clearly more people receiving placebo showed no
      improvement in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI
      0.40 to 0.97, very low quality evidence). Benzodiazepines versus
      antipsychoticsWhen compared with haloperidol, there was no observed effect for
      benzodiazepines for sedation by 16 hours (n = 434, 8 RCTs, RR 1.13, 95% CI 0.83
      to 1.54, low quality evidence). There was no difference in the number of
      participants who had not improved in the medium term (n = 188, 5 RCTs, RR 0.89,
      95% CI 0.71 to 1.11, low quality evidence). However, one small study found fewer
      participants improved when receiving benzodiazepines compared with olanzapine (n
      = 150, 1 RCT, RR 1.84, 95% CI 1.06 to 3.18, very low quality evidence). People
      receiving benzodiazepines were less likely to experience extrapyramidal effects
      in the medium term compared to people receiving haloperidol (n = 233, 6 RCTs, RR
      0.13, 95% CI 0.04 to 0.41, low quality evidence).Benzodiazepines versus combined
      antipsychotics/antihistaminesWhen benzodiazepine was compared with combined
      antipsychotics/antihistamines (haloperidol plus promethazine), there was a higher
      risk of no improvement in people receiving benzodiazepines in the medium term (n
      = 200, 1 RCT, RR 2.17, 95% CI 1.16 to 4.05, low quality evidence). However, for
      sedation, the results were controversial between two groups: lorazepam may lead
      to lower risk of sedation than combined antipsychotics/antihistamines (n = 200, 1
      RCT, RR 0.91, 95% CI 0.84 to 0.98, low quality evidence); while, midazolam may
      lead to higher risk of sedation than combined antipsychotics/antihistamines (n =
      200, 1 RCT, RR 1.13, 95% CI 1.04 to 1.23, low quality evidence).Other
      combinationsData comparing benzodiazepines plus antipsychotics versus
      benzodiazepines alone did not yield any results with clear differences; all were
      very low quality evidence. When comparing combined benzodiazepines/antipsychotics
      (all studies compared haloperidol) with the same antipsychotics alone
      (haloperidol), there was no difference between groups in improvement in the
      medium term (n = 185, 4 RCTs, RR 1.17, 95% CI 0.93 to 1.46, low quality
      evidence), but sedation was more likely in people who received the combination
      therapy (n = 172, 3 RCTs, RR 1.75, 95% CI 1.14 to 2.67,very low quality
      evidence). Only one study compared combined benzodiazepine/antipsychotics with
      antipsychotics; however, this study did not report our primary outcomes. One
      small study compared combined benzodiazepines/antipsychotics with combined
      antihistamines/antipsychotics. Results showed a higher risk of no clinical
      improvement (n = 60, 1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality
      evidence) and sedation status (n = 60, 1 RCT, RR 12.00, 95% CI 1.66 to 86.59,
      very low quality evidence) in the combined benzodiazepines/antipsychotics group.
      AUTHORS' CONCLUSIONS: The evidence from RCTs for the use of benzodiazepines alone
      is not good. There were relatively few good data. Most trials were too small to
      highlight differences in either positive or negative effects. Adding a
      benzodiazepine to other drugs does not seem to confer clear advantage and has
      potential for adding unnecessary adverse effects. Sole use of older
      antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify.
      Much more high-quality research is still needed in this area.

PMID- 29219172
TI  - Roles of lipocalin 2 and adiponectin in iron overload cardiomyopathy.
AB  - Thalassemia is among the most common genetic diseases worldwide. Ineffective
      erythropoiesis, chronic hemolysis, and regular blood transfusion in thalassemia
      patients lead to increased iron burden. Iron overload cardiomyopathy is the most
      severe co-morbidity and most common cause of mortality in thalassemia patients.
      Although its associated mechanisms are still not completely understood, cellular
      iron mishandling, chronic inflammation, and oxidative stress appear to be the key
      processes involved. In order to acquire a more comprehensive insight of the
      impact of cardiac iron overload, these alterations need to be intensively
      investigated. This comprehensive mini-review focuses on two emergent molecules
      which have been shown to potentially play significant roles in iron overload
      cardiomyopathy. These two molecules are an iron-transporting protein, lipocalin
      2, and an anti-inflammatory adipokine, adiponectin. Reports from in vitro and in
      vivo studies are comprehensively summarized. Clinical studies examining the roles
      of these molecules in thalassemia patients are also presented and discussed.

PMID- 29219173
TI  - Parenting stress, anxiety, and depression in mothers with visually impaired
      infants: a cross-sectional and longitudinal cohort analysis.
AB  - AIM: This study examined cross-sectional and longitudinal patterns of parenting
      stress, adult anxiety, and depression in mothers of children with profound or
      severe visual impairment (PVI or SVI) at 1 year and 2 years of age. METHOD:
      Mothers of a national longitudinal cohort (OPTIMUM Project) of infants with
      congenital disorders of the peripheral visual system and PVI (light perception at
      best) or SVI (basic 'form' vision of non-light reflecting objects) participated.
      Infant age at baseline (T1 ) was 8 to 16 months. Mothers completed the Parenting
      Stress Index - Short Form and the Hospital Anxiety and Depression Scale at T1
      (n=79) and at follow-up 12 months later (T2 ) (n=73). RESULTS: Mothers of the
      total group had higher parenting stress levels (34.6% in clinical range) than
      community normative data at T1 (p=0.017). Mothers of infants in the PVI subgroup
      had elevated stress at T1 (p=0.014) and T2 (p=0.009). The PVI subgroup was also
      elevated in the Difficult Child subscale at T2 (p=0.001). Within-sample
      differences in parenting stress between the visual impairment subgroups were
      found at T2 only: the PVI subgroup scored higher than the SVI subgroup (p=0.029).
      Adult anxiety and depression in the total group were not elevated compared with
      community normative data at T1 and T2 ; however, higher parenting stress was
      related to raised adult anxiety and depression levels at T1 and T2 (p=0.001).
      Regression analysis found parenting stress and lower child vision level (T1 )
      predicted parenting stress (T2 ) (p=0.001; 42% variance). INTERPRETATION: Mothers
      of 1-year-old infants with visual impairment showed raised risk for parenting
      stress, which continued to be elevated for children with PVI and those perceived
      as 'difficult' at 2 years. This was also a psychological risk, with greater adult
      anxiety and depression in those mothers with raised parenting stress. The
      clinical significance is that identification of parenting stress and targeted
      parenting, and behavioural support of the child in the first years of life is
      highly indicated. WHAT THIS PAPER ADDS: Mothers of infants with visual impairment
      are at increased risk of parenting stress. Parenting stress was higher in mothers
      of children with profound visual impairment than those with severe visual
      impairment. High levels of parenting stress and lower infant vision at 1 year of
      age predicted higher parenting stress at 2 years of age.

PMID- 29219175
TI  - XIST/miR-544 axis induces neuropathic pain by activating STAT3 in a rat model.
AB  - An increasing number of studies have reported that lncRNAs are responsible for
      the development of neuropathic pain. In our current study, chronic constriction
      injury (CCI) rat models were established and we observed that lncRNA XIST was
      greatly increased. Knockdown of XIST can relieve pain characteristics including
      both mechanical and thermal hyperalgesia in CCI rats. Meanwhile, XIST down
      regulation could inhibit neuro-inflammation by reducing expression of
      inflammatory cytokines including tumor necrosis factor (TNF)-alpha, IL-1beta, and
      IL-6 and in CCI rats. By performing bioinformatics technology, miR-544 was
      predicted to have interactions with XIST and dual-luciferase reporter assays
      validated the correlation between them. A negative correlation between miR-544
      and XIST was observed by carrying out XIST loss or gain of function tests. miR
      544 markedly alleviated neuropathic pain development in CCI rats via targeting
      inflammatory cytokines, which was reversed by XIST over-expression. Moreover,
      STAT3 was manifested to be a target gene of miR-544 by bioinformatics predictions
      and it was activated in CCI rats. Over-expression of STAT3 was able to induce
      neuropathic pain and miR-544 inhibited this process in vivo. Furthermore, XIST
      increased STAT3 expression by sponging miR-544 in neuropathic pain development.
      To conclude, our present study indicated that XIST can contribute to neuropathic
      pain progression in rats through down-regulating miR-544 and up-regulating STAT3.
      Our results suggested that XIST/miR-544/STAT3 axis can serve as a novel
      therapeutic target in neuropathic pain development.

PMID- 29219174
TI  - IGFBP3 deposited in the human umbilical cord mesenchymal stem cell-secreted
      extracellular matrix promotes bone formation.
AB  - The extracellular matrix (ECM) contains rich biological cues for cell
      recruitment, proliferationm, and even differentiation. The osteoinductive
      potential of scaffolds could be enhanced through human bone marrow mesenchymal
      stem cell (hBMSC) directly depositing ECM on surface of scaffolds. However, the
      role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSC)
      secreted ECM in bone formation remain unknown. We tested the osteoinductive
      properties of a hUCMSC-secreted ECM construct (hUCMSC-ECM) in a large femur
      defect of a severe combined immunodeficiency (SCID) mouse model. The hUCMSC-ECM
      improved the colonization of endogenous MSCs and bone regeneration, similar to
      the hUCMSC-seeded scaffold and superior to the scaffold substrate. Besides, the
      hUCMSC-ECM enhanced the promigratory molecular expressions of the homing cells,
      including CCR2 and TbetaRI. Furthermore, the hUCMSC-ECM increased the number of
      migrated MSCs by nearly 3.3 +/- 0.1-fold, relative to the scaffold substrate. As
      the most abundant cytokine deposited in the hUCMSC-ECM, insulin-like growth
      factor binding protein 3 (IGFBP3) promoted hBMSC migration in the TbetaRI/II- and
      CCR2-dependent mechanisms. The hUCMSC-ECM integrating shRNA-mediated silencing of
      Igfbp3 that down-regulated IGFBP3 expression by approximately 60%, reduced the
      number of migrated hBMSCs by 47%. In vivo, the hUCMSC-ECM recruited 10-fold more
      endogenous MSCs to initiate bone formation compared to the scaffold substrate.
      The knock-down of Igfbp3 in the hUCMSC-ECM inhibited nearly 60% of MSC homing and
      bone regeneration capacity. This research demonstrates that IGFBP3 is an
      important MSC homing molecule and the therapeutic potential of hUCMSC-ECM in bone
      regeneration is enhanced by improving MSC homing in an IGFBP3-dependent
      mechanism.

PMID- 29219176
TI  - TET2 expression is a potential prognostic and predictive biomarker in
      cytogenetically normal acute myeloid leukemia.
AB  - TET2 (Ten-Eleven Translocation 2) gene is a member of TET family that can modify
      DNA through catalyzing the conversion of 5-methylcytosine (5-mC) into 5
      hydroxymethylcytosine (5-hmC). Although TET2 mutation has been disclosed in a
      variety of hematopoietic malignancies, the prognostic implication of TET2
      expression in acute myeloid leukemia (AML) remains largely elusive. In this
      study, real-time quantitative PCR was carried out to detect the level of TET2
      transcript in 134 de novo AML patients and 35 healthy donors. TET2 mRNA level was
      significantly down-regulated in AML patients compared with controls (p = 0.010).
      Among the French-American-British (FAB) subtypes, the incidence of TET2 under
      expression in M0/M1 subtypes was significantly higher than in the other subtypes
      M2/M3/M4/M5/M6 (p = 0.017), and also markedly higher than in the other
      granulocyte subtypes M2/M3 (p = 0.005). TET2 low-expressed patients showed a
      significantly higher frequency of NPM1 mutations than TET2 high-expressed
      patients. Although there was no significant difference in complete remission rate
      between two groups (low and high TET2 expression), patients with low TET2
      expression had markedly shorter overall survival (OS) in both non-M3 and
      cytogenetically normal AML (CN-AML) (p = 0.016 and 0.044, respectively).
      Furthermore, multivariate analysis confirmed the prognostic value of TET2
      expression on OS among CN-AML patients (p = 0.049). Importantly, TET2 expression
      in complete remission (CR) time was significantly higher than newly diagnosis
      time (p = 0.001), and was returned to lower level when in relapse time (p <
      0.001). These findings indicated that down-regulation of TET2 expression was a
      common event and acted as a prognostic and predictive biomarker in CN-AML
      patients.

PMID- 29219177
TI  - Current status and future prospective of Curcumin as a potential therapeutic
      agent in the treatment of colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common cause of cancer-related deaths
      worldwide. Hence there is a need to identify new therapeutic agents that improve
      the current repertoire of chemotherapeutic drugs. The antitumor activity of
      curcumin has been reported for several tumors, including CRC. A recent phase I
      trial showed that curcumin is safe and tolerable adjunct to FOLFOX (5
      fluorouracil, folinic acid and oxaliplatin) chemotherapy in patient-derived
      colorectal liver metastases at doses up to 2 g daily. Another trial revealed the
      effect of combining curcumin with FOLFOX in patients with inoperable colorectal
      cancer. The aim of current review was to summarize the current knowledge about
      possible molecular mechanisms of curcumin in CRC with particular emphasis on
      preclinical and early clinical studies of colorectal cancer.

PMID- 29219178
TI  - The long noncoding RNA NEAT1 contributes to hepatocellular carcinoma development
      by sponging miR-485 and enhancing the expression of the STAT3.
AB  - Accumulating evidence has supported the significance of lncRNAs in tumorigenesis.
      Recently, some studies indicate the oncogenic role of lncRNA Nuclear Enriched
      Abundant Transcript 1 (NEAT1) in hepatocellular carcinoma (HCC). In our present
      study, we focused on the biological mechanisms through which NEAT1 can regulate
      HCC development. We found that NEAT1 was greatly upregulated in human HCC cell
      lines including Huh7, Hep3B, HepG2, Bel-7404, and SK-Hep1 cells compared to the
      normal human liver cell line LO2. In addition, we observed that miR-485 was
      significantly downregulated in HCC cells. It was implied that miR-485 was
      increased by sh-NEAT1 and miR-485 can modulate NEAT1 expression negatively.
      Meanwhile, NEAT1inhibiton can repress HCC growth, migration, and invasion
      capacity in HepG2 and Hep3B cells. Through performing bioinformatic analysis,
      dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA
      pull-down assay, miR-485 was confirmed as a interacting target of NEAT1.
      Additionally, STAT3 was recognized as a direct target of miR-485 and miR-485
      mimics can inhibit STAT3 expression. It was demonstrated that NEAT1 can increase
      STAT3 levels while miR-485 mimics can repress STAT3. Moreover, we found that sh
      STAT3 was able to restrain HCC cell migration and invasion process. NEAT1 can act
      as a competing endogenous lncRNA (ceRNA) to regulated STAT3 by sponging miR-485
      in HCC. Taken these together, NEAT1 can be used as an important biomarker in HCC
      diagnosis and treatment.

PMID- 29219179
TI  - Multidrug resistant lncRNA profile in chemotherapeutic sensitive and resistant
      ovarian cancer cells.
AB  - Most ovarian cancer patients are chemosensitive initially, but finally relapse
      with acquired chemoresistance. Multidrug-resistance is the extremely terrible
      situation. The mechanism for the acquired chemoresistance of ovarian cancer
      patients is still not clear. LncRNAs have been recognized as the important
      regulator of a variety of biological processes, including the multidrug-resistant
      process. Here, we carried out the lncRNA sequencing of the ovarian cancer cell
      line A2780 and the paxitaxel resistant cell line A2780/PTX which is also cross
      resistant to the cisplatin and epirubicin. Through integrating the published data
      with the cisplatin resistant lncRNAs in ovarian cancer cell line or ovarian
      cancer patients, 5 up-regulated and 21 down-regulated lncRNAs are considered as
      the multidrug-resistant lncRNAs. By real-time PCR analysis, we confirmed the 5 up
      regulated and 4 down-regulated multidrug resistant lncRNAs were similarly changed
      in both the multidrug resistant ovarian cancer cell lines and the multidrug
      resistant colon cancer cell lines. Furthermore, we conducted the lncRNA-mRNA co
      expression network to predict the potential multidrug resistant lncRNAs' targets.
      Interestingly, the multidrug resistant genes ABCB1, ABCB4, ABCC3, and ABCG2 are
      all co-expressed with lncRNA CTD-2589M5.4. Our results provide the valuable
      information for the understanding of the lncRNA function in the multidrug
      resistant process.

PMID- 29219180
TI  - Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.
AB  - Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear
      stress that is crucial for endothelial functions. Laminar shear stress (LSS)
      exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for
      cellular survival. However, the effects of LSS on mitochondrial homeostasis in
      ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined.
      Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm2 ) generated
      by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an
      increment of mitochondria in tubular form coupled with the increase of fusion
      proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of
      both long- and short- OPA1 along with a higher protease YME1L level were
      observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of
      fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria
      was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion.
      Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of
      mitochondrial mass and its regulatory proeins (PGC1alpha, TFAM, Nrf1). LSS
      enhances the expression of mitochondrial antioxidant enzymes and improves
      mitochondrial functions indicated by the increase of mitochondrial membrane
      potential (DeltaPsim) and ATP generation. TNFalpha treatment decreased
      mitochondrial tubular network and its functions in ECs. LSS mitigated TNFalpha
      induced mitochondrial impairments in ECs. Our results clearly indicate that LSS
      promotes mitochondrial homeostasis and attenuates inflammation-induced
      mitochondrial impairments in ECs. Our results provide novel insights into the
      manner of mitochondrial dynamics and functions modulated by LSS that contribute
      to endothelial integrity.

PMID- 29219181
TI  - Exercise increases Rho-kinase activity and insulin signaling in skeletal muscle.
AB  - The effects of physical exercise on insulin signaling and glycemic homeostasis
      are not yet fully understood. Recent findings elucidated the positive role of Rho
      kinase (Rock) in increasing the glucose uptake through insulin receptor substrate
      1 (IRS1) phosphorylation in the skeletal muscle. Here, we explored the effects of
      short-term exercise on Rock activity and insulin signaling. Fischer 344 rats (3
      months old) were subjected to a short-term swimming exercise for 2 hr per day for
      5 days, with an overload corresponding to 1.5% of body weight. As expected, the
      exercised group had a reduced glycemia and increased insulin sensitivity. The
      contents of Rock1, Rock2, and Rock activity were improved in the skeletal muscle
      of the exercised rats. The contents of RhoA and RhoGEF, which are proteins
      involved in the Rock metabolism, were also increased in the skeletal muscle after
      exercise. These changes in the protein contents were accompanied by an increase
      in the insulin signaling pathway (pIRS1/pPDK/pAkt/pGSK3beta/pAS160/GLUT4), Rock
      activity, and IRS1 phosphorylation at the 632/635 serine residues. On the other
      hand, when Rock was inhibited with the Y-27632, the insulin sensitivity in
      response to exercise was impaired. Based on these findings, we conclude that the
      short-term exercise increased both insulin sensitivity and glucose tolerance,
      through the increased Rock activity and pIRS1 (serine 632/635) mediated by Rock,
      in the skeletal muscle of Fischer 344 rats. These data represent an exercise
      mediated novel mechanism, suggesting an essential role of Rock activity in the
      insulin signaling and glucose homeostasis improvement.

PMID- 29219182
TI  - The emerging role of Hippo signaling pathway in regulating osteoclast formation.
AB  - A delicate balance between osteoblastic bone formation and osteoclastic bone
      resorption is crucial for bone homeostasis. This process is regulated by the
      Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2,
      SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo
      signaling pathway plays an important part in regulating osteoblast
      differentiation, but its role in osteoclast formation and activation remains
      poorly understood. In this review, we discuss the emerging role of Hippo
      signaling pathway in osteoclast formation and bone homeostasis. It is revealed
      that specific molecules of the Hippo-signaling pathway take part in a stage
      specific regulation in pre-osteoclast proliferation, osteoclast differentiation
      and osteoclast apoptosis and survival. Upon activation, MST and LAST,
      transcriptional co-activators YAP and TAZ bind to the members of the TEA domain
      (TEAD) family transcription factors, and influence osteoclast differentiation via
      regulating the expression of downstream target genes such as connective tissue
      growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition,
      through interacting or cross talking with RANKL-mediated signaling cascades
      including NF-kappaB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as
      YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate
      osteoclast differentiation and function. Elucidating the roles of the Hippo
      signaling pathway in osteoclast development and specific molecules involved is
      important for understanding the mechanism of bone homeostasis and diseases.

PMID- 29219183
TI  - Mechanical unloading reduces microtubule actin crosslinking factor 1 expression
      to inhibit beta-catenin signaling and osteoblast proliferation.
AB  - Mechanical unloading was considered a major threat to bone homeostasis, and has
      been shown to decrease osteoblast proliferation although the underlying mechanism
      is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal
      protein that regulates cellular processes and Wnt/beta-catenin pathway, an
      essential signaling pathway for osteoblasts. However, the relationship between
      MACF1 expression and mechanical unloading, and the function and the associated
      mechanisms of MACF1 in regulating osteoblast proliferation are unclear. This
      study investigated effects of mechanical unloading on MACF1 expression levels in
      cultured MC3T3-E1 osteoblastic cells and in femurs of mice with hind limb
      unloading; and it also examined the role and potential action mechanisms of MACF1
      in osteoblast proliferation in MACF1-knockdown, overexpressed or control MC3T3-E1
      cells treated with or without the mechanical unloading condition. Results showed
      that the mechanical unloading condition inhibited osteoblast proliferation and
      MACF1 expression in MC3T3-E1 osteoblastic cells and mouse femurs. MACF1 knockdown
      decreased osteoblast proliferation, while MACF1 overexpression increased it. The
      inhibitory effect of mechanical unloading on osteoblast proliferation also
      changed with MACF1 expression levels. Furthermore, MACF1 was found to enhance
      beta-catenin expression and activity, and mechanical unloading decreased beta
      catenin expression through MACF1. Moreover, beta-catenin was found an important
      regulator of osteoblast proliferation, as its preservation by treatment with its
      agonist lithium attenuated the inhibitory effects of MACF1-knockdown or
      mechanical unloading on osteoblast proliferation. Taken together, mechanical
      unloading decreases MACF1 expression, and MACF1 up-regulates osteoblast
      proliferation through enhancing beta-catenin signaling. This study has thus
      provided a mechanism for mechanical unloading-induced inhibited osteoblast
      proliferation.

PMID- 29219184
TI  - Minimal clinically important difference of voice handicap index-10 in vocal fold
      paralysis.
AB  - OBJECTIVES/HYPOTHESIS: The Voice Handicap Index-10 (VHI-10) is commonly used to
      measure patients' perception of vocal handicap. Clinical consensus has previously
      defined clinically meaningful improvement as a decrease >=5. This study
      determines the minimal clinically important difference (MCID) for VHI-10 in
      patients with unilateral vocal fold paralysis (UVFP) using anchor-based
      methodology. STUDY DESIGN: Prospective cohort questionnaire analysis. METHODS:
      Two hundred eighty-one UVFP patients completed the VHI-10 on two consecutive
      visits (within 3 months). At the follow-up visit, patients answered an 11-point
      Global Rating of Change Questionnaire (GRCQ) scored from -5 to +5. Relationship
      between the GRCQ and change in VHI-10 was quantified using analysis of variance,
      and MCID for the VHI-10 was determined using receiver operating characteristic
      (ROC) curve analysis. RESULTS: Overall mean VHI-10 change was -3.71 (standard
      deviation [SD] = 8.89) and mean GRCQ was 1.37 (SD = 2.51). Average interval
      between measurements was 1.73 months (SD = 0.83). Mean changes in VHI-10 scores
      were -7.45, -0.53, and +4.40 for patients whose GRCQ scores indicated
      improvement, no change, and worsening, respectively. Differences between mean
      scores were statistically significant (P < .001). Area under the ROC curve was
      0.80, demonstrating the classification accuracy of VHI-10 change scores. A VHI-10
      change of -4 was determined to be the optimal threshold that discriminated
      between improvement and no improvement (sensitivity and specificity 0.62 and
      0.88, respectively). CONCLUSIONS: The MCID for improvement in VHI-10 in UVFP
      patients is a decrease of 4. This information improves understanding of patients'
      response to treatment and allows comparison between different treatments. Future
      research should determine MCID for VHI-10 across all voice disorders. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:1419-1424, 2018.

PMID- 29219185
TI  - The development and validation of the speech quality instrument.
AB  - OBJECTIVE: Although speech perception tests are available to evaluate hearing,
      there is no standardized validated tool to quantify speech quality. The objective
      of this study is to develop a validated tool to measure quality of speech heard.
      STUDY DESIGN: Prospective instrument validation study of 35 normal hearing adults
      recruited at a tertiary referral center. METHODS: Participants listened to 44
      speech clips of male/female voices reciting the Rainbow Passage. Speech clips
      included original and manipulated excerpts capturing goal qualities such as
      mechanical and garbled. Listeners rated clips on a 10-point visual analog scale
      (VAS) of 18 characteristics (e.g. cartoonish, garbled). RESULTS: Skewed
      distribution analysis identified mean ratings in the upper and lower 2-point
      limits of the VAS (ratings of 8-10, 0-2, respectively); items with inconsistent
      responses were eliminated. The test was pruned to a final instrument of nine
      speech clips that clearly define qualities of interest: speech-like, male/female,
      cartoonish, echo-y, garbled, tinny, mechanical, rough, breathy, soothing, hoarse,
      like, pleasant, natural. Mean ratings were highest for original female clips
      (8.8) and lowest for not-speech manipulation (2.1). Factor analysis identified
      two subsets of characteristics: internal consistency demonstrated Cronbach's
      alpha of 0.95 and 0.82 per subset. Test-retest reliability of total scores was
      high, with an intraclass correlation coefficient of 0.76. CONCLUSION: The Speech
      Quality Instrument (SQI) is a concise, valid tool for assessing speech quality as
      an indicator for hearing performance. SQI may be a valuable outcome measure for
      cochlear implant recipients who, despite achieving excellent speech perception,
      often experience poor speech quality. LEVEL OF EVIDENCE: 2b. Laryngoscope,
      128:1622-1627, 2018.

PMID- 29219186
TI  - Improved adductor function after canine recurrent laryngeal nerve injury and
      repair using muscle progenitor cells.
AB  - OBJECTIVE: Muscle progenitor cells (MPCs) can be isolated from muscle samples and
      grown to a critical mass in culture. They have been shown to survive and
      integrate when implanted into rat laryngeal muscles. In this study, the ability
      of MPC implants to enhance adductor function of reinnervated thyroarytenoid
      muscles was tested in a canine model. STUDY DESIGN: Animal study. METHODS:
      Sternocleidomastoid muscle samples were harvested from three canines. Muscle
      progenitor cells were isolated and cultured to 107 cells over 4 to 5 weeks, then
      implanted into right thyroarytenoid muscles after ipsilateral recurrent laryngeal
      nerve transection and repair. The left sides underwent the same nerve injury, but
      no cells were implanted. Laryngeal adductor force was measured pretreatment and
      again 6 months later, and the muscles were harvested for histology. RESULTS:
      Muscle progenitor cells were successfully cultured from all dogs. Laryngeal
      adductor force measurements averaged 60% of their baseline pretreatment values in
      nonimplanted controls, 98% after implantation with MPCs, and 128% after
      implantation with motor endplate-enhanced MPCs. Histology confirmed that the
      implanted MPCs survived, became integrated into thyroarytenoid muscle fibers, and
      were in close contact with nerve endings, suggesting functional innervation.
      CONCLUSION: Muscle progenitor cells were shown to significantly enhance adductor
      function in this pilot canine study. Patient-specific MPC implantation could
      potentially be used to improve laryngeal function in patients with vocal fold
      paresis/paralysis, atrophy, and other conditions. Further experiments are
      planned. LEVEL OF EVIDENCE: NA. Laryngoscope, 2017.

PMID- 29219187
TI  - Integrated molecular, biochemical, and physiological assessment unravels key
      extraction method mediated influences on rat neonatal cardiomyocytes.
AB  - Neonatal cardiomyocytes are instrumental for disease modeling, but the effects of
      different cell extraction methods on basic cell biological processes remain
      poorly understood. We assessed the influence of two popular methods to extract
      rat neonatal cardiomyocytes, Pre-plating (PP), and Percoll (PC) on cell
      structure, metabolism, and function. Cardiomyocytes obtained from PP showed
      higher gene expression for troponins, titin, and potassium and sodium channels
      compared to PC. Also, PP cells displayed higher levels of troponin I protein.
      Cells obtained from PC displayed higher lactate dehydrogenase activity and
      lactate production than PP cells, indicating higher anaerobic metabolism after 8
      days of culture. In contrast, reactive oxygen species levels were higher in PP
      cells as indicated by ethidium and hydroxyethidium production. Consistent with
      these data, protein nitration was higher in PP cells, as well as nitrite
      accumulation in cell medium. Moreover, PP cells showed higher global
      intracellular calcium under basal and 1 mM isoprenaline conditions. In a calcium
      transient assessment under electrical stimulation (0.5 Hz), PP cells displayed
      higher calcium amplitude than cardiomyocytes obtained from PC and using a
      traction force microscope technique we observed that PP cardiomyocytes showed the
      highest relaxation. Collectively, we demonstrated that extraction methods
      influence parameters related to cell structure, metabolism, and function.
      Overall, PP derived cells are more active and mature than PC cells, displaying
      higher contractile function and generating more reactive oxygen species. On the
      other hand, PC derived cells display higher anaerobic metabolism, despite
      comparable high yields from both protocols.

PMID- 29219188
TI  - Toxicity trial of canine posterior cricoarytenoid intramuscular vincristine
      injections.
AB  - OBJECTIVES/HYPOTHESIS: In animal studies, intramuscular vincristine injections
      have been shown to block reinnervation of the denervated target muscle. This
      application could be used selectively to influence recovery patterns following
      injury of recurrent laryngeal nerves (RLNs). However, vincristine is currently
      Food and Drug Administration approved only for intravenous use. A formal toxicity
      trial of intramuscular injections was performed. STUDY DESIGN: Animal study.
      METHODS: Sixteen female canines underwent direct laryngoscopy with injection of
      moderate- (0.4 mg, n = 8) or high-dose (0.6 mg, n = 8) vincristine into the
      posterior cricoarytenoid (PCA) muscles. Plasma samples were collected at various
      time points postinjection and vincristine levels determined. At 24 hours (n = 7)
      or 14 days (n = 9) postinjection, animals were anesthetized and videolaryngoscopy
      documented vocal fold mobility and mucosal appearance. Adductor function was
      measured during stimulation of the RLN. Larynges were processed for histology.
      RESULTS: Fifteen minutes after injection, plasma vincristine levels averaged
      10.2% +/- 6.7% of the intravenous maximum, suggesting about 90% of the
      vincristine remained within the PCA muscle. Plasma levels were usually below
      detectable limits within 24 hours. At the end points, all animals had grossly
      normal-appearing mucosa and full range of motion. Laryngeal adductor strength was
      normal in all cases. Histology showed moderate to severe acute inflammation in
      the submucosa only in the high-dose group at 24 hours. There was no necrosis of
      muscle or mucosa. CONCLUSIONS: Intramuscular vincristine injections into the
      canine PCA muscles resulted in no significant local toxicity, even at the maximum
      dose. It would be reasonable to evaluate this treatment strategy in a phase I
      human trial. LEVEL OF EVIDENCE: NA Laryngoscope, 128:E247-E250, 2018.

PMID- 29219189
TI  - Breast cancer diagnosis: Imaging techniques and biochemical markers.
AB  - Breast cancer is a complex disease which is found as the second cause of cancer
      associated death among women. Accumulating of evidence indicated that various
      factors (i.e., gentical and envirmental factors) could be associated with
      initiation and progression of breast cancer. Diagnosis of breast cancer patients
      in early stages is one of important aspects of breast cancer treatment. Among of
      various diagnosis platforms, imaging techniques are main diagnosis approaches
      which could provide valuable data on patients with breast cancer. It has been
      showed that various imaging techniques such as mammography, magnetic resonance
      imaging (MRI), positron-emission tomography (PET), Computed tomography (CT), and
      single-photon emission computed tomography (SPECT) could be used for diagnosis
      and monitoring patients with breast cancer in various stages. Beside, imaging
      techniques, utilization of biochemical biomarkers such as proteins, DNAs, mRNAs,
      and microRNAs could be employed as new diagnosis and therapeutic tools for
      patients with breast cancer. Here, we summarized various imaging techniques and
      biochemical biomarkers could be utilized as diagnosis of patients with breast
      cancer. Moreover, we highlighted microRNAs and exosomes as new diagnosis and
      therapeutic biomarkers for monitoring patients with breast cancer.

PMID- 29219191
TI  - The development of the human hyoid-larynx complex revisited.
AB  - OBJECTIVES/HYPOTHESIS: The hyoid-larynx complex is highly prone to anatomical
      variation. The etiology of anatomical variants such as Eagle's syndrome and the
      aberrant hyoid apparatus can be explained from embryonic development. Modern
      textbooks state that the hyoid bone body develops from the second and third
      pharyngeal arch cartilages, and that thyroid cartilage derives from the fourth
      and sixth arch cartilages. This description, however, is incompatible with
      various anatomical variants, and it is unclear whether it was based on
      observations in human embryos or on comparative embryology. STUDY DESIGN: 14
      human embryos from the Carnegie collection between Carnegie stage 17 and 23 (42
      60 days) were selected based on their histological quality. METHODS: Histological
      sections of the selected embryos were examined. Three-dimensional models were
      prepared in an interactive format. These anatomical models provide crucial
      spatial information and facilitate interpretation. RESULTS: We observed a less
      complicated development of the hyoid-larynx complex than is currently described
      in textbooks. The body of the hyoid bone originates from a single growth center,
      without overt contributions from second and third pharyngeal arch cartilages. The
      fourth and sixth arch cartilages were not detected in human embryos; the thyroid
      and cricoid cartilages develop as mesenchymal condensations in the neck region.
      CONCLUSIONS: Despite new research techniques, theories about hyoid-larynx complex
      development from the beginning of the 20th century have not been refuted properly
      and can still be found in modern literature. Based on observations in human
      embryos, we propose a new and relatively simple description of the development of
      the hyoid-larynx complex to facilitate better understanding of the etiology of
      anatomical variants. LEVEL OF EVIDENCE: NA Laryngoscope, 1829-1834, 2018.

PMID- 29219192
TI  - What is the appropriate timing for endoscopic and radiographic surveillance
      following treatment for sinonasal malignancies?

PMID- 29219193
TI  - The effect of horizontal and vertical furcation involvement on molar survival: A
      retrospective study.
AB  - BACKGROUND: Periodontal involvement of the furcation area (furcation involvement,
      FI) has been reported to confer molars a higher risk of tooth loss. AIMS: The aim
      of this retrospective analysis was to assess the effect of FI on disease
      progression and tooth loss in molars of patients with chronic periodontitis
      undergoing supportive periodontal therapy (SPT) in a UK private practice setting.
      MATERIALS AND METHODS: Six-hundred and thirty-three molars were analysed in 100
      chronic periodontitis patients treated with active periodontal therapy (APT) and
      followed up in SPT for at least 5 years. Molars were treated with a combination
      of resective, regenerative or conservative approaches, according to the different
      clinical needs. RESULTS: Twenty-three molars were extracted during APT and a
      further 23 were lost during SPT. Multivariable analysis showed that both
      horizontal FI and vertical furcation component were associated with increased
      risk of tooth loss during SPT (OR 5.26, 95% CI: 1.46-19.03, p = .012 and OR 9.83,
      95% CI: 1.83-50.11, p = .006, respectively). CONCLUSION: Attention should be
      placed on both horizontal and vertical FI in molars, owing to their association
      with tooth loss during SPT.

PMID- 29219190
TI  - Phenomenology, genetics, and CNS network abnormalities in laryngeal dystonia: A
      30-year experience.
AB  - OBJECTIVE: Laryngeal dystonia (LD) is a functionally specific disorder of the
      afferent-efferent motor coordination system producing action-induced muscle
      contraction with a varied phenomenology. This report of long-term studies aims to
      review and better define the phenomenology and central nervous system
      abnormalities of this disorder and improve diagnosis and treatment. METHODS: Our
      studies categorized over 1,400 patients diagnosed with LD over the past 33 years,
      including demographic and medical history records and their phenomenological
      presentations. Patients were grouped on clinical phenotype (adductor or abductor)
      and genotype (sporadic and familial) and with DNA analysis and functional
      magnetic resonance imaging (fMRI) to investigate brain organization differences
      and characterize neural markers for genotype/phenotype categorization. A number
      of patients with alcohol-sensitive dystonia were also studied. RESULTS: A
      spectrum of LD phenomena evolved: adductor, abductor, mixed, singer's, dystonic
      tremor, and adductor respiratory dystonia. Patients were genetically screened for
      DYT (dystonia) 1, DYT4, DYT6, and DYT25 (GNAL)-and several were positive. The
      functional MRI studies showed distinct alterations within the sensorimotor
      network, and the LD patients with a family history had distinct cortical and
      cerebellar abnormalities. A linear discriminant analysis of fMRI findings showed
      a 71% accuracy in characterizing LD from normal and in characterizing adductor
      from abductor forms. CONCLUSION: Continuous studies of LD patients over 30 years
      has led to an improved understanding of the phenomenological characteristics of
      this neurological disorder. Genetic and fMRI studies have better characterized
      the disorder and raise the possibility of making objective rather than subjective
      diagnoses, potentially leading to new therapeutic approaches. Laryngoscope,
      128:S1-S9, 2018.

PMID- 29219194
TI  - Natural Mentors, Social Class, and College Success.
AB  - Natural mentors provide advice, moral support, and assistance to adolescents who
      aspire to obtain a postsecondary degree, but past studies of the benefits of
      having an informal adult mentor have yet to resolve several issues. Our analyses
      of a national sample of high school graduates test three hypotheses: (H1) natural
      mentoring increases the odds of college attendance and completion, (H2) guidance
      and career advice are more important for college success than encouragement or
      role modeling, and (H3) students from poor and working-class families benefit
      more from mentoring than students from middle- and upper-class families.
      Hypotheses 1 and 3 are clearly supported when examining the odds of attending
      college, while Hypothesis 2 was not supported-encouragement and role modeling
      boost attendance, not advice or practical help. None of the hypotheses is
      supported when predicting degree completion among those who matriculated. As
      natural mentors do not appreciably increase the odds of completing college, we
      conclude past studies have overstated the postsecondary educational benefits of
      natural mentors.

PMID- 29219195
TI  - Dissecting the 17beta-estradiol pathways necessary for neuroglobin anti-apoptotic
      activity in breast cancer.
AB  - Neuroglobin (NGB) is a relatively recent discovered monomeric heme-protein, which
      behave in neurons as a sensor of injuring stimuli including oxidative stress,
      hypoxia, and neurotoxicity. In addition, the anti-apoptotic activity of
      overexpressed NGB has been reported both in neurons and in cancer cell lines. We
      recently demonstrated that, NGB functions as a compensatory protein of the
      steroid hormone 17beta-estradiol (E2) protecting cancer cells against the
      apoptotic death induced by oxidative stress. However, the E2-induced signaling
      pathways at the root of NGB over-expression and mitochondrial re-localization in
      breast cancer cells is still elusive. By using a kinase screening library, here,
      we report that: i) There is a strong positive correlation between NGB and ERalpha
      expression and activity in breast cancer cells; ii) The E2-activated phosphatidyl
      inositol 3 kinase (PI3K)/protein kinase B (AKT) and protein kinase C (PKC)
      pathways are necessary to modulate the NGB protein levels; iii) The E2-induced
      persistent activation of AKT drive NGB to mitochondria; iv) Reactive oxygen
      species (ROS)-inducing compounds activating rapidly and transiently AKT does not
      affect the NGB mitochondrial level; and v) High level of NGB into mitochondria
      are necessary for the pro-survival and anti-apoptotic effect of this globin in
      cancer cells. As a whole, these results underline the E2 triggered pathways in E2
      responsive breast cancer cells that involve NGB as a compensatory protein devoted
      to cancer cell survival.

PMID- 29219196
TI  - Evaluation of efficacy of repeated decontamination and sterilization of single
      incision laparoscopic surgery ports intended for 1-time use.
AB  - OBJECTIVE: To determine the efficacy of repeated decontamination and
      sterilization of a disposable port intended for 1-time use during single-incision
      laparoscopy. STUDY DESIGN: Experimental; prospective, controlled design. METHODS:
      Six single-access ports used 4 times and 6 single-access ports used 8 times to
      perform various clean, minimally invasive surgeries were evaluated. Ports were
      decontaminated in an enzymatic cleaner (dilution, 3:100) and cleaned with a scrub
      brush for 5 minutes. The ports were then sterilized with hydrogen peroxide vapor
      for 50 minutes using a standard protocol at a concentration of 6 mg/L, followed
      by a vapor diffusion phase. Samples taken from the foam, insufflating tubing, and
      rigid cannula portion of each port were collected with aseptic technique for
      aerobic-anaerobic cultures. Port material samples were set up on a tryptic soy
      agar plate with 5% sheep blood, a MacConkey agar plate, and a Columbia agar plate
      with 5% sheep blood (CAP). Anaerobic isolate cultures were set up on Centers for
      Disease Control and Prevention (CDC) blood agar and CAP. RESULTS: None of the
      ports used 4 times had positive bacteriologic culture. Two of the ports used 8
      times had a light growth of bacteria. The first positive sample cultured
      Staphylococcus spp. and Micrococcus spp. The second positive sample cultured
      Staphylococcus epidermidis. The positive cultures were obtained from the foam
      component in an enriched broth. CONCLUSION: Single-incision ports could be used
      safely 4 times and pose a low risk of infection to the patient under conditions
      of this study.

PMID- 29219197
TI  - Comparison of Ultrasound-Guided Percutaneous Polidocanol Injection Versus
      Percutaneous Ethanol Injection for Treatment of Benign Cystic Thyroid Nodules.
AB  - OBJECTIVES: We compared the efficacy, safety, and cost-effectiveness of
      ultrasound-guided percutaneous polidocanol injection and percutaneous ethanol
      injection for the treatment of benign cystic and predominantly cystic thyroid
      nodules. METHODS: A total of 135 cystic thyroid nodules treated by percutaneous
      ethanol injection and 136 cystic thyroid nodules treated by percutaneous
      polidocanol injection were enrolled retrospectively in this study from May 2010
      to March 2016. The nodules were followed after 1, 3, 6, and 12 months. Nodule
      volumes, symptoms scores, and cosmetic scores were assessed before treatment and
      at follow-up. The therapeutic success rate, safety, and cost-effectiveness
      between the groups were also compared. RESULTS: No significant differences in the
      reduction of the nodule volume, volume reduction rate, and therapeutic success
      were observed between the groups with cystic and predominantly cystic thyroid
      nodules during follow-up (P > .05). Neither the cosmetic scores (P = .59; P =
      .42) nor the symptom scores (P = .32; P = .73) in the cystic and predominantly
      cystic nodules were significantly different between the groups at the last follow
      up. The complication rates for ethanol were higher than those for polidocanol (P
      < .05). However, the cost of polidocanol injection was higher than that of
      ethanol injection for cystic thyroid nodules (mean +/- SD, US$97.18 +/- US$22.17
      versus US$43.36 +/- US$5.51; P < .01). CONCLUSIONS: Ultrasound-guided
      percutaneous polidocanol injection can be an alternative for sclerotherapy of
      cystic or predominantly cystic thyroid nodules. However, its cost was higher than
      that of percutaneous ethanol injection.

PMID- 29219198
TI  - Spontaneous neurotransmission: A form of neural communication comes of age.

PMID- 29219199
TI  - Variable transcriptional responsiveness of the P2X3 receptor gene during CFA
      induced inflammatory hyperalgesia.
AB  - The purinergic receptor P2X3 (P2X3-R) plays important roles in molecular pathways
      of pain, and reduction of its activity or expression effectively reduces chronic
      inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and
      cancer-induced pain can increase P2X3-R mRNA and/or protein levels in dorsal root
      ganglia (DRG). However, P2X3-R expression is unaltered or even reduced in other
      pain studies. The reasons for these discrepancies are unknown and might depend on
      the applied traumatic intervention or on intrinsic factors such as age, gender,
      genetic background, and/or epigenetics. In this study, we sought to get insights
      into the molecular mechanisms responsible for inflammatory hyperalgesia by
      determining P2X3-R expression in DRG neurons of juvenile male rats that received
      a Complete Freund's Adjuvant (CFA) bilateral paw injection. We demonstrate that
      all CFA-treated rats showed inflammatory hyperalgesia, however, only a fraction
      (14-20%) displayed increased P2X3-R mRNA levels, reproducible across both sides.
      Immunostaining assays did not reveal significant increases in the percentage of
      P2X3-positive neurons, indicating that increased P2X3-R at DRG somas is not
      critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin
      immunoprecipitation (ChIP) assays showed a correlated (R2  = 0.671) enrichment of
      the transcription factor Runx1 and the epigenetic active mark histone H3
      acetylation (H3Ac) at the P2X3-R gene promoter in a fraction of the CFA-treated
      rats. These results suggest that animal-specific increases in P2X3-R mRNA levels
      are likely associated with the genetic/epigenetic context of the P2X3-R locus
      that controls P2X3-R gene transcription by recruiting Runx1 and epigenetic co
      regulators that mediate histone acetylation.

PMID- 29219201
TI  - Comparing Physical Examination With Sonographic Versions of the Same Examination
      Techniques for Splenomegaly.
AB  - OBJECTIVES: To determine whether sonographic versions of physical examination
      techniques can accurately identify splenomegaly, Castell's method (Ann Intern Med
      1967; 67:1265-1267), the sonographic Castell's method, spleen tip palpation, and
      the sonographic spleen tip technique were compared with reference measurements.
      METHODS: Two clinicians trained in bedside sonography patients recruited from an
      urban hematology clinic. Each patient was examined for splenomegaly using
      conventional percussion and palpation techniques (Castell's method and spleen tip
      palpation, respectively), as well as the sonographic versions of these maneuvers
      (sonographic Castell's method and sonographic spleen tip technique). Results were
      compared with a reference standard based on professional sonographer
      measurements. RESULTS: The sonographic Castell's method had greater sensitivity
      (91.7% [95% confidence interval, 61.5% to 99.8%]) than the traditional Castell's
      method (83.3% [95% confidence interval, 51.6% to 97.9%]) but took longer to
      perform [mean +/- SD, 28.8 +/- 18.6 versus 18.8 +/- 8.1 seconds; P = .01).
      Palpable and positive sonographic spleen tip results were both 100% specific, but
      the sonographic spleen tip method was more sensitive (58.3% [95% confidence
      interval, 27.7% to 84.8%] versus 33.3% [95% confidence interval, 9.9% to 65.1%]).
      CONCLUSIONS: Sonographic versions of traditional physical examination maneuvers
      have greater diagnostic accuracy than the physical examination maneuvers from
      which they are derived but may take longer to perform. We recommend a combination
      of traditional physical examination and sonographic techniques when evaluating
      for splenomegaly at the bedside.

PMID- 29219200
TI  - Prediction of Tubal Ectopic Pregnancy Using Offline Analysis of 3-Dimensional
      Transvaginal Ultrasonographic Data Sets: An Interobserver and Diagnostic Accuracy
      Study.
AB  - OBJECTIVES: To assess interobserver reproducibility in detecting tubal ectopic
      pregnancies by reading data sets from 3-dimensional (3D) transvaginal
      ultrasonography (TVUS) and comparing it with real-time 2-dimensional (2D) TVUS.
      METHODS: Images were initially classified as showing pregnancies of unknown
      location or tubal ectopic pregnancies on real time 2D TVUS by an experienced
      sonologist, who acquired 5 3D volumes. Data sets were analyzed offline by 5
      observers who had to classify each case as ectopic pregnancy or pregnancy of
      unknown location. The interobserver reproducibility was evaluated by the Fleiss
      kappa statistic. The performance of each observer in predicting ectopic
      pregnancies was compared to that of the experienced sonologist. Women were
      followed until they were reclassified as follows: (1) failed pregnancy of unknown
      location; (2) intrauterine pregnancy; (3) ectopic pregnancy; or (4) persistent
      pregnancy of unknown location. RESULTS: Sixty-one women were included. The
      agreement between reading offline 3D data sets and the first real-time 2D TVUS
      was very good (80%-82%; kappa = 0.89). The overall interobserver agreement among
      observers reading offline 3D data sets was moderate (kappa = 0.52). The
      diagnostic performance of experienced observers reading offline 3D data sets had
      accuracy of 78.3% to 85.0%, sensitivity of 66.7% to 81.3%, specificity of 79.5%
      to 88.4%, positive predictive value of 57.1% to 72.2%, and negative predictive
      value of 87.5% to 91.3%, compared to the experienced sonologist's real-time 2D
      TVUS: accuracy of 94.5%, sensitivity of 94.4%, specificity of 94.5%, positive
      predictive value of 85.0%, and negative predictive value of 98.1%. CONCLUSIONS:
      The diagnostic accuracy of 3D TVUS by reading offline data sets for predicting
      ectopic pregnancies is dependent on experience. Reading only static 3D data sets
      without clinical information does not match the diagnostic performance of real
      time 2D TVUS combined with clinical information obtained during the scan.

PMID- 29219202
TI  - Disturbance of gut satiety peptide in purging disorder.
AB  - OBJECTIVE: Little is known about biological factors that contribute to purging
      after normal amounts of food-the central feature of purging disorder (PD). This
      study comes from a series of nested studies examining ingestive behaviors in
      bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the
      hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp)
      (n = 26), and controls (n = 26). Based on distinct subjective responses to a
      fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether
      postprandial PYY response was significantly greater and ghrelin levels
      significantly lower in women with PD compared to controls and women with BNp.
      METHOD: Participants completed structured clinical interviews, self-report
      questionnaires, and laboratory assessments of gut peptide and subjective
      responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly
      greater postprandial PYY response compared to women with BNp and controls, who
      did not differ significantly. PD women also endorsed significantly greater
      gastrointestinal distress, and PYY predicted gastrointestinal intestinal
      distress. Ghrelin levels were significantly greater in PD and BNp compared to
      controls, but did not differ significantly between eating disorders. Women with
      BNp endorsed significantly greater postprandial hunger, and ghrelin predicted
      hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response.
      Findings contribute to growing evidence of physiological distinctions between PD
      and BNp. Future research should examine whether these distinctions account for
      differences in clinical presentation as this could inform the development of
      specific interventions for patients with PD.

PMID- 29219203
TI  - Automated QT analysis on Holter monitors in pediatric patients can differentiate
      long QT syndrome from controls.
AB  - BACKGROUND: Borderline QTc is a common referral to the pediatric cardiology
      clinic. Evaluation is challenging due to significant overlap of normal and
      abnormal QTc ranges. We hypothesized that automated QT analysis on Holter could
      differentiate between patients with long QT syndrome (LQTS) and healthy controls.
      METHODS: We conducted a retrospective review of 39 patients with known genotype
      positive, phenotype-positive LQTS who underwent Holter monitoring between January
      2010 and January 2016. They were compared 2:1 to age- and sex-matched controls.
      Automated QT analysis data were analyzed. RESULTS: Significant differences were
      found in all automated QT and QTc fields, except minimum QTc interval (P = 0.57).
      Mean QTc interval (LQTS 479 +/- 28 ms vs controls 429 +/- 16 ms; P <= 0.001) and
      percent QTc intervals (%QTc) >450 ms (LQTS 80 +/- 28% vs controls 14 +/- 16%; P
      <= 0.001) were selected for further analysis. A receiver operating characteristic
      curve was generated for each variable demonstrating high area under the curve
      values of 0.9494 and 0.9540, respectively. Threshold values of >=461 ms for mean
      QTc (sensitivity 79.49%, specificity 98.72%) and >=65% of %QTc >450 ms
      (sensitivity 79.49%, specificity 98.72%) allowed highly specific discrimination
      between cohorts (false positive rate 1.09%). Similarly, thresholds of <434 ms
      (sensitivity 97.44, specificity 61.54) for mean QTc and <32% (sensitivity 89.74,
      specificity 87.18) for %QTc >450 ms resulted in highly sensitive discrimination
      (false negative rates 2.17% and 8.7%). CONCLUSION: Holter monitor testing with
      automated QT analysis may be a useful tool to differentiate LQTS and control
      patients.

PMID- 29219204
TI  - Textile Inspired Lithium-Oxygen Battery Cathode with Decoupled Oxygen and
      Electrolyte Pathways.
AB  - The lithium-air (Li-O2 ) battery has been deemed one of the most promising next
      generation energy-storage devices due to its ultrahigh energy density. However,
      in conventional porous carbon-air cathodes, the oxygen gas and electrolyte often
      compete for transport pathways, which limit battery performance. Here, a novel
      textile-based air cathode is developed with a triple-phase structure to improve
      overall battery performance. The hierarchical structure of the conductive textile
      network leads to decoupled pathways for oxygen gas and electrolyte: oxygen flows
      through the woven mesh while the electrolyte diffuses along the textile fibers.
      Due to noncompetitive transport, the textile-based Li-O2 cathode exhibits a high
      discharge capacity of 8.6 mAh cm-2 , a low overpotential of 1.15 V, and stable
      operation exceeding 50 cycles. The textile-based structure can be applied to a
      range of applications (fuel cells, water splitting, and redox flow batteries)
      that involve multiple phase reactions. The reported decoupled transport pathway
      design also spurs potential toward flexible/wearable Li-O2 batteries.

PMID- 29219205
TI  - The iron-deficient rat as a model of restless legs syndrome: Was anything lost in
      translation?

PMID- 29219206
TI  - Neuroprotective Effects of Antioxidants in the Management of Neurodegenerative
      Disorders: A Literature Review.
AB  - It is proven that oxidative stress has a pivotal role in the process of
      neurodegeneration. The use of antioxidants is an attractive method to prevent the
      incidence of neurodegenerative diseases. We searched major databases (PubMed, Med
      Line and Google Scholar) using the keywords of neurodegeneration, oxidative
      stress, and antioxidant for both review and original studies which have reported
      the various beneficial effects of antioxidants. About 70 studies were identified
      for this review. Among various antioxidants, 9 antioxidants with the most
      applications in research investigations were selected and the major findings
      concerning their protective effects were reviewed. It is concluded that
      antioxidants can modify and re-adjust the oxidative stress in the biological
      milieu, elicit neuroprotective effects, and positively impact themanagement of
      neurodegenerative processes. This article is protected by copyright. All rights
      reserved.

PMID- 29219207
TI  - Motor complications in Parkinson's disease: Striatal molecular and
      electrophysiological mechanisms of dyskinesias.
AB  - Long-term levodopa (l-dopa) treatment in patients with Parkinson's disease (PD)
      is associated with the development of motor complications (ie, motor fluctuations
      and dyskinesias). The principal etiopathogenic factors are the degree of nigro
      striatal dopaminergic loss and the duration and dose of l-dopa treatment. In this
      review article we concentrate on analysis of the mechanisms underlying l-dopa
      induced dyskinesias, a phenomenon that causes disability in a proportion of
      patients and that has not benefited from major therapeutic advances. Thus, we
      discuss the main neurotransmitters, receptors, and pathways that have been
      thought to play a role in l-dopa-induced dyskinesias from the perspective of
      basic neuroscience studies. Some important advances in deciphering the molecular
      pathways involved in these abnormal movements have occurred in recent years to
      reveal potential targets that could be used for therapeutic purposes. However, it
      has not been an easy road because there have been a plethora of components
      involved in the generation of these undesired movements, even bypassing the
      traditional and well-accepted dopamine receptor activation, as recently revealed
      by optogenetics. Here, we attempt to unify the available data with the hope of
      guiding and fostering future research in the field of striatal activation and
      abnormal movement generation. (c) 2017 International Parkinson and Movement
      Disorder Society.

PMID- 29219208
TI  - LncRNA H19 promotes epithelial-mesenchymal transition (EMT) by targeting miR-484
      in human lung cancer cells.
AB  - Recently, the long non-coding RNA (lncRNA) H19 has been identified as an
      oncogenic gene in multiple cancer types. However, the molecular basis for this
      observation has not been characterized in lung cancer, especially during
      epithelial mesenchymal transition (EMT) progression. Cell viability, migration,
      invasion, and apoptosis were measured using trypan blue exclusion assay,
      Transwell migration/invasion assay, and flow cytometry, respectively.
      Quantitative RT-PCR was used to measure relative expressions of H19, microR-484
      (miR-484), and Rho associated coiled-coil containing protein kinase 2 (ROCK2).
      Western blot was used to measure expressions of apoptosis-, EMT-, and c-Jun N
      terminal kinase (JNK) pathway-related proteins. Luciferase reporter assay was
      used to identify the target of H19. H19 was highly expressed in both lung cancer
      tissues and cells. Suppression of H19 significantly decreased A549 cell
      viability, migration, and invasion, but promoted apoptosis. Overexpression of H19
      promoted cell migration, invasion, and EMT process. miR-484 was a target of H19
      and overexpression of it reversed the effects of H19 on EMT. miR-484 regulated
      the expression of ROCK2. Mechanistic study revealed that suppressing H19
      decreased the expression of proteins in JNK pathway, and ROCK2 was the main
      downstream molecule of H19. H19 promoted EMT in lung cancer A549 cells by
      negatively regulating miR-484.

PMID- 29219209
TI  - Warfarin Use And the Risk Of Stroke, Bleeding, And Mortality In Older Adults On
      Dialysis With Incident Atrial Fibrillation.
AB  - AIM: There is conflicting evidence regarding the safety and effectiveness of
      warfarin for atrial fibrillation (AF) treatment among older end-stage renal
      disease (ESRD) patients, and differences among subgroups are unclear. METHODS:
      Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were
      identified in the United States Renal Data System. The adjusted hazard ratios
      (HR) of the outcomes (any stroke, ischemic stroke, major bleeding, severe
      gastrointestinal bleeding, and death) by time-varying warfarin use were estimated
      using Cox regression accounting for the inverse probability of treatment weight.
      RESULTS: Among 5,765 older dialysis patients with incident AF, warfarin was
      associated with significantly increased risk of major bleeding (HR=1.50, 95% CI
      1.33-1.68), but was not statistically associated with any stroke (HR=0.92, 95% CI
      0.75-1.12), ischemic stroke (HR=0.88, 95%CI 0.70-1.11) or gastrointestinal
      bleeding (HR=1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced
      risk of mortality (HR=0.72, 95%CI 0.65-0.80). The association between warfarin
      and major bleeding differed by sex (male: HR=1.29; 95%CI 1.08-1.55; female:
      HR=1.67; 95%CI 1.44-1.93; P-value for interaction=0.03). CONCLUSION: Older ESRD
      patients with AF who were treated with warfarin had a no difference in stroke
      risk, lower mortality risk, but increased major bleeding risk. The bleeding risk
      associated with warfarin was greater among women than men. The risk/benefit ratio
      of warfarin may be less favorable among older women.

PMID- 29219211
TI  - Homoepitaxial Growth of Large-Scale Highly Organized Transition Metal
      Dichalcogenide Patterns.
AB  - Controllable growth of highly crystalline transition metal dichalcogenide (TMD)
      patterns with regular morphology and unique edge structure is highly desired and
      important for fundamental research and potential applications. Here, single
      crystalline MoS2 flakes are reported with regular trigonal symmetric patterns
      that can be homoepitaxially grown on MoS2 monolayer via chemical vapor
      deposition. The highly organized MoS2 patterns are rhombohedral (3R)-stacked with
      the underlying MoS2 monolayer, and their boundaries are predominantly terminated
      by zigzag Mo edge structure. The epitaxial MoS2 crystals can be tailored from
      compact triangles to fractal flakes, and the pattern formation can be explained
      by the anisotropic growth rates of the S and Mo edges under low sulfur chemical
      potential. The 3R-stacked MoS2 pattern demonstrates strong second and third
      harmonic-generation signals, which exceed those reported for monolayer MoS2 by a
      factor of 6 and 4, correspondingly. This homoepitaxial growth approach for making
      highly organized TMD patterns is also demonstrated for WS2 .

PMID- 29219210
TI  - Bioenergetic regulation of microglia.
AB  - Microglia have diverse actions, ranging from synapse pruning in development to
      cytotoxic effects in disease. Brain energy metabolism and substrate availability
      vary under normal and disease states, but how these variations influence
      microglial function is relatively unknown. Microglia, like most other cell types,
      express the full complement of gene products required for both glycolytic and
      oxidative metabolism. Evidence suggests that microglia increase aerobic
      glycolysis and decrease respiration when activated by various stimuli.
      Mitochondrial function, glucose availability, and glycolytic rate influence pro
      inflammatory gene expression at both transcriptional and post-translational
      levels. These effects are mediated through CtBP, an NADH-sensitive
      transcriptional co-repressor; through effects on NLRP3 inflammasome assembly and
      caspase-1 activation; through formation of advanced glycation end-products; and
      by less well-defined mechanisms. In addition to these transcriptional effects,
      microglial glucose metabolism is also required for superoxide production by NADPH
      oxidase, as glucose is the obligate substrate for regenerating NADPH in the
      hexose monophosphate shunt. Microglia also metabolize acetoacetate and beta
      hydroxybutyrate, which are generated during fasting or ketogenic diet, and
      respond to these ketones as metabolic signals. beta-Hydroxybutyrate inhibits
      histone de-acetylases and activates microglial GRP109A receptors. These actions
      suppress microglia activation after brain injury and promote neuroprotective
      microglia phenotypes. As our understanding of microglial activation matures,
      additional links between energy metabolism and microglial function are likely to
      be identified.

PMID- 29219212
TI  - Host miRNAs are involved in hormonal regulation of HaSNPV-triggered climbing
      behaviour in Helicoverpa armigera.
AB  - Baculoviruses manipulate host climbing behaviour to ensure that the hosts die at
      elevated positions on host plants to facilitate virus proliferation and
      transmission, which is a process referred to as tree-top disease. However, the
      detailed molecular mechanism underlying tree-top disease has not been elucidated.
      Using transcriptome analysis, we showed that two hormone signals, juvenile
      hormone (JH) and 20-hydroxyecdysone (20E), are key components involved in HaSNPV
      induced tree-top disease in Helicoverpa armigera larvae. RNAi-mediated knockdown
      and exogenous hormone treatment assays demonstrated that 20E inhibits virus
      induced tree-top disease, while JH mediates tree-top disease behaviour. Knockdown
      of BrZ2, a downstream signal of JH and 20E, promoted HaSNPV-induced tree-top
      disease. We also found that two miRNAs target BrZ2 and are involved in the cross
      talk regulation between 20E and JH manipulating HaSNPV replication, time to death
      and HaSNPV-induced tree-top disease.

PMID- 29219213
TI  - Effect of a Pheromone on Stress-Associated Reactivation of Feline Herpesvirus-1
      in Experimentally Inoculated Kittens.
AB  - BACKGROUND: Stress contributes to reactivation of feline herpesvirus-1 (FHV-1).
      The usage of pheromones to decrease stress in FHV-1 experimentally inoculated
      kittens has not previously been investigated. HYPOTHESIS/OBJECTIVES: To determine
      whether a feline pheromone would lessen stress, resulting in decreased recurrence
      of FHV-1-associated illness in kittens. ANIMALS: Twelve 5-month-old, purpose-bred
      kittens. METHODS: Randomized, double-blind, placebo-controlled clinical trial.
      Kittens previously infected with the same dose of FHV-1 were randomized into 2
      separate but identical group rooms. After a 2-week equilibration period, a
      diffuser containing either the pheromone or placebo was placed in each of the
      rooms, and the kittens acclimated for an additional 2 weeks. Every 2 weeks
      thereafter, for the 8-week study period, housing was alternated between kennel-
      and group housing. Blinded observers applied a standardized clinical and
      behavioral scoring rubric daily. After each 2-week period, serum cortisol
      concentrations and quantitative PCR for FHV-1 and glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) ratios were evaluated. Clinical, behavioral, and laboratory
      test results were compared between groups within individual and combined study
      periods. RESULTS: Sneezing occurred more frequently in the placebo group during
      individual (P = 0.006) and combined study periods (P = 0.001). Sleep at the end
      of observation periods occurred more frequently in the pheromone group during
      individual (P = 0.006) and combined study periods (P < 0.001). CONCLUSIONS AND
      CLINICAL IMPORTANCE: The findings suggest that the pheromone decreased stress,
      and the decrease in stress response may have resulted in decreased sneezing
      associated with FHV-1.

PMID- 29219214
TI  - Whole exome sequencing identifies a germline MET mutation in two siblings with
      hereditary wild-type RET medullary thyroid cancer.
AB  - Whole exome sequencing (WES) was used to investigate two Italian siblings with
      wild-type RET genotype, who developed medullary thyroid cancers (MTCs) and,
      later, primary prostate and breast cancers, respectively. The proband's MTC
      harbored a p.Met918Thr RET mutation; his sister's MTC was RET/RAS wild-type. Both
      siblings had a germline mutation (p.Arg417Gln) in the extracellular Sema domain
      of the proto-oncogene MET. Experiments involving ectopic expression of MET
      p.Arg417Gln in MET-negative T47D breast cancer cells documented the mutant
      receptor's functionality and its ability to enhance cell migration and invasion.
      Our findings highlight a possible link between MET germline mutations and MTCs
      and suggest that MET p. Arg417Gln may promote an invasive malignant phenotype.
      The possibility that MTC can be driven/co-driven by a MET mutation has potential
      management implications, since the tyrosine-kinase inhibitor cabozantinib
      approved for treating advanced MTCs-is a specific MET inhibitor.

PMID- 29219215
TI  - Wound healing activity of Streptocaulon juventas root ethanolic extract.
AB  - Streptocaulon juventas is a well-known plant that has antimicrobial activity, in
      vitro antiplasmodial activity, anti-proliferative activity, and antioxidant
      activity. In this study, we showed experimental evidence that proved that S.
      juventas root ethanolic extract has wound healing activities. First, in a mouse
      excision wound model, S. juventas root ethanolic extract at a dose of 100
      mg/kg/day significantly reduced the wound closure time. After 7 days, the wound
      granulation tissue in mice treated with the extract exhibited a 2.3-fold decrease
      in inflammatory cells, a 1.7-fold increase in fibroblasts and enhanced
      angiogenesis. Molecular analysis also revealed that after wounds were treated
      with S. juventas root ethanolic extract, TNF-alpha and NF-kappaB1 gene expression
      were down-regulated by 4.7 and 3.7 times, respectively. In contrast, TGF-beta1
      and VEGF gene expression were up-regulated by 1.9 and 6.5 times, respectively.
      Taken together, our experimental data strongly show that the ethanolic extract
      from S. juventas root displays remarkable wound healing activity.

PMID- 29219216
TI  - Knockdown of long non-coding RNA XIST suppresses nasopharyngeal carcinoma
      progression by activating miR-491-5p.
AB  - Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles
      in the development and progression of human cancers. X-inactive specific
      transcript (XIST), an lncRNA, is known as an oncogene in multiple tumors.
      However, the roles of XIST and its related miRNAs in nasopharyngeal carcinoma
      (NPC) are poorly understood. In this study, we found that XIST expression was
      significantly upregulated in NPC tissues and cell lines. Knockdown of XIST
      inhibited NPC cell proliferation and invasion and induced apoptosis in vitro, as
      well as suppressed NPC tumor growth in vivo. Further analysis revealed that XIST
      and miR-491-5p interact with and repress each other. XIST may function as an
      endogenous miR-491-5p sponge to regulate the target gene of miR-491-5p. Taken
      together, these results provide a comprehensive view of the XIST/miR-491-5p axis
      in human NPC cells and may provide a new therapeutic target for treating NPC.

PMID- 29219217
TI  - Environmentally Friendly Solvent-Processed Organic Solar Cells that are Highly
      Efficient and Adaptable for the Blade-Coating Method.
AB  - The power conversion efficiencies (PCEs) of state-of-the-art organic solar cells
      (OSCs) have increased to over 13%. However, the most commonly used solvents for
      making the solutions of photoactive materials and the coating methods used in
      laboratories are not adaptable for future practical production. Therefore, taking
      a solution-coating method with environmentally friendly processing solvents into
      consideration is critical for the practical utilization of OSC technology. In
      this study, a highly efficient PBTA-TF:IT-M-based device processed with
      environmentally friendly solvents, tetrahydrofuran/isopropyl alcohol (THF/IPA)
      and o-xylene/1-phenylnaphthalene, is fabricated; a high PCE of 13.1% can be
      achieved by adopting the spin-coating method, which is the top result for OSCs.
      More importantly, a blade-coated non-fullerene OSC processed with THF/IPA is
      demonstrated for the first time to obtain a promising PCE of 11.7%; even for the
      THF/IPA-processed large-area device (1.0 cm2 ) made by blade-coating, a PCE of
      10.6% can still be maintained. These results are critical for the large-scale
      production of highly efficient OSCs in future studies.

PMID- 29219218
TI  - Rotator cuff tendon assessment using magic-angle insensitive 3D ultrashort echo
      time cones magnetization transfer (UTE-Cones-MT) imaging and modeling with
      histological correlation.
AB  - BACKGROUND: Rotator cuff tendons (RCTs) are challenging to image due to the
      "magic angle effect" and their short T2 . PURPOSE: To assess the degree of magic
      angle sensitivity of human RCTs and to utilize a 3D ultrashort echo time Cones
      sequence with magnetization transfer preparation (UTE-Cones-MT) and two-pool
      quantitative MT modeling with histological correlation. We hypothesized that MT
      parameters would be less sensitive to the magic angle compared with conventional
      T2 measurements. STUDY TYPE: Prospective imaging pathologic correlation.
      SPECIMEN: Twenty cadaveric rotator cuff tendons were imaged at five sample
      orientations ranging from 0-90 degrees  relative to the B0 field. FIELD
      STRENGTH/SEQUENCE: 3T/3D UTE-Cones-MT and Carr-Purcell-Meiboom-Gill (CPMG).
      ASSESSMENT: Two-pool quantitative MT modeling parameters and T2 values were
      calculated in regions of interest drawn by a medical physicist. Histopathological
      analysis was performed and mild and severe tendinopathy groups were assigned by a
      histopathologist and histotechnician. STATISTICAL TESTS: Coefficients of
      variations (CVs) were calculated for measures between the different orientations
      and group means were compared for each measure. RESULTS: CVs of T2 and
      macromolecular fractions between orientations were 26.14 +/- 16.82% and 6.18 +/-
      2.77% (mean +/- SD), respectively. T2 measurements at 0 degrees , 27 degrees , 70
      degrees , and 90 degrees  showed significant differences between the two
      histological groups (P = 0.004, 0.008, 0.003, and 0.015, respectively), but not
      at 55 degrees  (P = 0.611). Mean T2 value ranges between orientations for the
      mild and severe tendinopathy groups were 15.27-30.32 msec and 20.81-35.85 msec,
      respectively, showing overlap despite statistically significant differences (P =
      0.003). Macromolecular fractions at all angles showed significant differences
      between the two groups (P < 0.0001). Mean fraction ranges between orientations
      for the mild and severe tendinopathy groups were 14.32-17.17% and 10.00-13.75%
      respectively (P < 0.0001) with no overlap. DATA CONCLUSION: Compared with T2 ,
      macromolecular fraction obtained with the 3D UTE-Cones-MT technique is resistant
      to the magic angle effect and is more sensitive to RCT degeneration. LEVEL OF
      EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

PMID- 29219219
TI  - Ultrahigh-Magnitude Brain Magnetic Resonance Imaging Scan on Rhesus Monkeys With
      Implanted Deep Brain Stimulation Hardware.
AB  - BACKGROUND: Patients with implanted deep brain stimulation (DBS) hardware are
      prohibited from undergoing magnetic resonance imaging (MRI) scans at magnitudes
      greater than 1.5 T to avoid potential MRI-related heating injury. Whether DBS
      devices are compatible with higher field MRI scanning is unknown. This study
      aimed to investigate whether 7.0 T and 3.0 T MRI scans can be safely performed on
      rhesus monkeys with implanted DBS devices. METHODS: Eight male rhesus monkeys
      were included in this study and stereotactically implanted with DBS devices in
      the left anterior thalamus. Two weeks after DBS device implantation, 7.0 T and
      3.0 T MRI scans were performed. The monkeys were observed for 72 hours. After
      explantation of the DBS system, 7.0 T MRI was repeated to determine potential
      lesions. Hematoxylin and eosin staining and transmission electron microscopy were
      conducted to assess pathological alterations. RESULTS: In both groups, the
      monkeys exhibited no behavioral changes related to neurological deficits. Post
      explantation MRI showed no malacia foci surrounding the DBS tracks. Additionally,
      neither hematoxylin and eosin staining nor transmission electron microscopy
      showed clear injury near the DBS leads. CONCLUSION: These results indicate that
      no obvious heating injury was induced in the tissue surrounding the DBS leads by
      the 7.0 T and 3.0 T MRI scans. Although the results of this study may not be
      generalizable, these data suggest that patients with implanted DBS devices can
      undergo even 7.0 T MRI without risk of brain injury.

PMID- 29219220
TI  - Heart rate recovery fast-to-slow phase transition: Influence of physical fitness
      and exercise intensity.
AB  - BACKGROUND: Postexercise heart rate (HR) recovery presents an exponential decay,
      with two distinct phases: a fast phase, characterized by abrupt decay of HR, and
      determined by parasympathetic reactivation; and a slow phase, characterized by
      gradual decay of HR, and predominantly determined by sympathetic withdrawal.
      Although several methods have been proposed to assess postexercise HR recovery,
      none of those methods selectively assesses the time of transition from the fast
      to the slow phase of the HR recovery curve (HRRPT ), and the magnitude of decay
      prior to (HRRFP ) and after this point (HRRSP ). Therefore, the aim of the
      present study was to propose a method to identify HRRPT , HRRFP , and HRRSP and
      to verify the effects of exercise intensity and physical fitness on such
      parameters. METHODS: Ten healthy young participants (24 +/- 3 years; 23.6 +/- 1.7
      kg/m2 ) randomly underwent two exercise sessions (30 min of cycling), at moderate
      (MI) and high intensity (HI); followed by 5 min of inactive recovery. HR was
      continuously recorded during the sessions. The algorithm for HRRPT analysis was
      written in Python and is freely available online. RESULTS: HRRPT and HRRSP were
      increased in HI session compared with MI (81 +/- 24 vs. 60 +/- 20 s; 8 +/- 10 vs.
      1 +/- 5 bpm; p = .04), and there was no difference in HRRFP between sessions (49
      +/- 15 vs. 46 +/- 10 bpm; p = .17). In addition, HRRPT for MI exercise session
      was significantly and negatively associated with VO2max (r = -0.85, p < .05).
      CONCLUSION: The method herein presented was sensitive to exercise intensity, and
      partially responsive to aerobic fitness. Next studies should perform the
      pharmacological and clinical validations of the method.

PMID- 29219221
TI  - Improved developmental competence in embryos treated with lycopene during in
      vitro culture system.
AB  - In vitro embryo development remains suboptimal compared to in vivo development
      due to the challenge from various stressors associated with in vitro culturing of
      oocytes. When 0.2 MUM lycopene was added to oocyte in vitro maturation and embryo
      culture media, to assess its antioxidant effects on embryo development, we
      observed a significant (p < 0.05) increase in cleavage and blastocyst development
      rates compared to the corresponding controls (84.3 +/- 0.6% vs. 73.1 +/- 1.9% and
      41.0 +/- 1.4% vs. 33.4 +/- 0.7%, respectively). Lycopene also significantly
      reduced (p < 0.05) intracellular reactive oxygen species concentrations in
      oocytes and blastocysts, whereas lipid peroxidation and mitochondrial activity
      increased compared to control conditions. The number of apoptotic nuclei was
      significantly reduced in the lycopene-treated compared to the control group (1.7
      +/- 0.1 vs. 4.7 +/- 0.3), and the quantity of cells in the trophectoderm (207.1
      +/- 1.6 vs. 171.3 +/- 1.0, respectively) and inner cell mass (41.9 +/- 0.4 vs.
      36.7 +/- 0.4, respectively) was higher following treatment-although the inner
      cell mass-to-trophectoderm ratio was unchanged (1:3.3 vs. 1:3.4 for lycopene vs.
      control, respectively). Lycopene supplementation also significantly (p < 0.05)
      attenuated expression of IKBKB (Inhibitor of nuclear factor kappa B kinase,
      subunit beta) and reduced Caspase 9 and Caspase 3 protein abundance, while up
      regulating GDF9 (Growth and differentiation factor 9), BMP15 (Bone morphogenetic
      protein 15), SOD2 (Superoxide dismutase 2), NDUFA2 (NADH dehydrogenase), ACADL
      (Acyl-CoA dehydrogenase, long chain), and ACSL3 (Acyl-CoA synthetase 3, long
      chain membrane 3) transcription compared to control. Therefore, co-culturing with
      lycopene during oocyte maturation improved bovine embryo developmental potential
      during in vitro culture by improving embryonic resilience to stress.

PMID- 29219222
TI  - Evidence for a Cooperative Mechanism Involving Two Palladium(0) Centers in the
      Oxidative Addition of Iodoarenes.
AB  - Oxidative addition of iodoarenes (ArI) to Pd0 ligated by 1-methyl-1H-imidazole
      (mim) in polar solvents leads to cationic arylpalladium(II) complexes [ArPd(mim)3
      ]+ . Kinetic analyses evidence that this reaction is second order with respect to
      the concentration of Pd0 , and a mechanism involving the cooperative intervention
      of two Pd0 centers has been postulated to explain this finding. This unusual
      behavior is also observed with other nitrogen-containing ligands and it is
      general for iodobenzenes substituted with electron-donating or weakly electron
      withdrawing groups. In contrast, bromoarenes and electron-poor iodoarenes display
      first-order kinetics with respect to Pd0 . Theoretical calculations performed at
      the density functional theory (DFT) level suggest the existence of mim-ligated
      ArI-Pd0 complexes, in which the iodoarene is bound to the metal in a halogen-bond
      like fashion. Coordination weakens the C-I bond and facilitates the oxidative
      insertion of another Pd0 center across this C-I bond. This conceptually novel
      mechanism, involving the cooperative participation of two distinct metal centers,
      allows a full explanation of the experimentally observed kinetics.

PMID- 29219223
TI  - Benzothiazole-Based Cycloplatinated Chromophores: Synthetic, Optical, and
      Biological Studies.
AB  - Cycloplatinated complexes based on 2-(4-substituted)benzothiazole ligands of type
      [Pt(R-PBT-kappaC,N)Cl(L)] (PBT=2-phenylbenzothiazole; R=Br (1), Me2 N (2);
      L=dimethyl sulfoxide (DMSO; a), 1,3,5- triaza-7-phosphaadamantane (PTA; b),
      triphenylphosphine 3,3',3''-trisulfonate (TPPTS; c)) and [Pt(Br-PBT
      kappaC)Cl(PTA)2 ] (3) are presented. On the basis of the photophysical data and
      time-dependent (TD)-DFT calculations (1 a and 2 a), the low-lying transitions
      (absorption and emission) were associated with ligand-center (LC) charge
      transfer, with minor metal-to-ligand charge transfer (MLCT), and intraligand
      charge transfer (ILCT) [Me2 N-PBT->PBT] excited states, respectively.
      Simultaneous fluorescence/phosphorescence bands were found in fluid solutions
      (and also in the solid state for 2 a), which become dominated by triplet emission
      bands in rigid media at 77 K. The effect of the concentration on emissive
      behavior of 2 a, b indicated the occurrence of aggregation-induced luminescence
      properties related to the occurrence of metal-metal and pi???pi interactions,
      which are more enhanced in 2 a because of the less bulky DMSO ligand. The
      behavior of 2 a toward para-toluenesulfonic acid (PTSA) in aerated acetonitrile
      and to hydrogen chloride gas in the solid state has been evaluated, thus showing
      a clear reversible change between the 1 ILCT and 3 LC/3 MLCT states due to
      protonation of the NMe2 group (theoretical calculations on 2 a-H+ ). Solid 2 a
      undergoes a surprising oxidation of the PtII center to PtIV with concomitant
      deoxygenation of DMSO, under prolonged reaction with hydrogen chloride gas to
      afford the PtIV /dimethyl sulfide complex (mer-[Pt(Me2 N-PBT-kappaC,N)Cl3 (SMe2
      )]; mer-4), which evolves in solution to fac-4, as confirmed by X-ray studies.
      Cytotoxic activity studies on A549 and HeLa cell lines indicated cytotoxic
      activity of 1 b and 2 a, b. In addition, fluorescent cell microscopy revealed
      cytoplasmic staining, more visible in perinuclear areas. Inhibition of tubulin
      polymerization by 1 b in both cells is presented as a preliminary mechanism of
      its cytotoxic action.

PMID- 29219224
TI  - The effects of pastoral intensification on the feeding interactions of generalist
      predators in streams.
AB  - Land-use change can alter trophic interactions with wide-ranging functional
      consequences, yet the consequences for aquatic food webs have been little
      studied. In part, this may reflect the challenges of resolving the diets of
      aquatic organisms using classical gut contents analysis, especially for soft
      bodied prey. We used next-generation sequencing to resolve prey use in nearly 400
      individuals of two predatory invertebrates (the Caddisfly, Rhyacophila dorsalis,
      and the Stonefly Dinocras cephalotes) in streams draining land with increasingly
      intensive livestock farming. Rhyacophila dorsalis occurred in all streams,
      whereas D. cephalotes was restricted to low intensities, allowing us to test
      whether: (i) apparent sensitivity to agriculture in the latter species reflects a
      more specialized diet and (ii) diet in R. dorsalis varied between sites with and
      without D. cephalotes. DNA was extracted from dissected gut contents, amplified
      without blocking probes and sequenced using Ion Torrent technology. Both
      predators were generalists, consuming 30 prey taxa with a preference for taxa
      that were abundant in all streams or that increased with intensification. Where
      both predators were present, their diets were nearly identical, and R. dorsalis's
      diet was virtually unchanged in the absence of D. cephalotes. The loss of D.
      cephalotes from more intensive sites was probably due to physicochemical
      stressors, such as sedimentation, rather than to dietary specialization, although
      wider biotic factors (e.g., competition with other predatory taxa) could not be
      excluded. This study provides a uniquely detailed description of predator diets
      along a land-use intensity gradient, offering new insights into how anthropogenic
      stressors affect stream communities.

PMID- 29219225
TI  - DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67
      status of estrogen receptor-positive breast cancers.
AB  - BACKGROUND: Breast tumor heterogeneity is related to risk factors that lead to
      worse prognosis, yet such heterogeneity has not been well studied. PURPOSE: To
      predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer
      patients via analysis of tumor heterogeneity with subgroup identification based
      on patterns of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
      STUDY TYPE: Retrospective study. POPULATION: Seventy-seven breast cancer patients
      with ER-positive breast cancer were investigated, of whom 51 had low Ki-67
      expression. FIELD STRENGTH/SEQUENCE: T1 -weighted 3.0T DCE-MR images. ASSESSMENT:
      Each tumor was partitioned into multiple subregions using three methods based on
      patterns of dynamic enhancement: 1) time to peak (TTP), 2) peak enhancement rate
      (PER), and 3) kinetic pattern clustering (KPC). In each tumor subregion, 18
      texture features were computed. STATISTICAL TESTING: Univariate and multivariate
      logistic regression analyses were performed using a leave-one-out-based cross
      validation (LOOCV) method. The partitioning results were compared with the same
      feature extraction methods across the whole tumor. RESULTS: In the univariate
      analysis, the best-performing feature was the texture statistic of sum variance
      in the tumor subregion with early TTP for differentiating between patients with
      high and low Ki-67 expression (area under the receiver operating characteristic
      curves, AUC = 0.748). Multivariate analysis showed that features from the tumor
      subregion associated with early TTP yielded the highest performance (AUC = 0.807)
      among the subregions for predicting the Ki-67 status. Among all regions, the
      tumor area with high PER at a precontrast MR image achieved the highest
      performance (AUC = 0.722), while the subregion that exhibited the highest overall
      enhancement rate based on KPC had an AUC of 0.731. These three models based on
      intratumoral texture analysis significantly (P < 0.01) outperformed the model
      using features from the whole tumor (AUC = 0.59). DATA CONCLUSION: Texture
      analysis of intratumoral heterogeneity has the potential to serve as a valuable
      clinical marker to enhance the prediction of breast cancer prognosis. LEVEL OF
      EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

PMID- 29219226
TI  - Getting there and around: Host range oscillations during colonization of the
      Canary Islands by the parasitic nematode Spauligodon.
AB  - Episodes of expansion and isolation in geographic range over space and time,
      during which parasites have the opportunity to expand their host range, are
      linked to the development of host-parasite mosaic assemblages and parasite
      diversification. In this study, we investigated whether island colonization
      events lead to host range oscillations in a taxon of host-specific parasitic
      nematodes of the genus Spauligodon in the Canary Islands. We further investigated
      whether range oscillations also resulted in shifts in host breadth (i.e.,
      specialization), as expected for parasites on islands. Parasite phylogeny and
      divergence time estimates were inferred from molecular data with Bayesian
      methods. Host divergence times were set as calibration priors after a priori
      evaluation with a global-fit method of which individual host-parasite
      associations likely represent cospeciation links. Parasite colonization history
      was reconstructed, followed by an estimation of oscillation events and
      specificity level. The results indicate the presence of four Spauligodon clades
      in the Canary Islands, which originated from at least three different
      colonization events. We found evidence of host range oscillations to truly novel
      hosts, which in one case led to higher diversification. Contemporary host
      parasite associations show strong host specificity, suggesting that changes in
      host breadth were limited to the shift period. Lineages with more frequent and
      wider taxonomic host range oscillations prior to the initial colonization event
      showed wider range oscillations during colonization and diversification within
      the archipelago. Our results suggest that a lineage's evolutionary past may be
      the best indicator of a parasite's potential for future range expansions.

PMID- 29219227
TI  - Rhodium-Catalyzed Cyclization of O,omega-Unsaturated Alkoxyamines: Formation of
      Oxygen-Containing Heterocycles.
AB  - O,omega-Unsaturated N-tosyl alkoxyamines undergo unexpected RhIII -catalyzed
      intramolecular cyclization by oxyamination to produce oxygen-containing
      heterocycles. Mechanistic studies show that an aziridine intermediate seems to be
      responsible for the formation of the heterocycles, possibly via a RhV species.

PMID- 29219228
TI  - Structure and function of yeast and fungal Na+ /H+ antiporters.
AB  - Sodium proton antiporters (or sodium proton exchangers [NHEs]) are a critical
      family of membrane proteins that exchange sodium for protons across cell
      membranes. In yeast and plants, their primary function is to keep the sodium
      concentration low inside the cytoplasm. One class of NHE constitutively expressed
      in yeast is the plasma membrane Na+ /H+ antiporter, and another class is
      expressed on the endosomal/vacuolar membrane. At present, four bacterial plasma
      membrane antiporter structures are known and nuclear magnetic resonance
      structures are available for the membrane spanning transmembrane helices of
      mammalian and yeast NHEs. Additionally, a vast amount of mutational data are
      available on the role of individual amino acids and critical motifs involved in
      transport. We combine this information to obtain a more detailed picture of the
      yeast NHE plasma membrane protein and review mechanisms of transport, conserved
      motifs, unique residues important in function, and regulation of these proteins.
      The Na+ /H+ antiporter of Schizosaccharomyces pombe, SpNHE1, is an interesting
      model protein in an easy to study system and is representative of fungal Na+ /H+
      antiporters. (c) IUBMB Life, 70(1):23-31, 2018.

PMID- 29219229
TI  - Characterisation of CYP102A25 from Bacillus marmarensis and CYP102A26 from
      Pontibacillus halophilus: P450 Homologues of BM3 with Preference towards
      Hydroxylation of Medium-Chain Fatty Acids.
AB  - Cytochrome P450 monooxygenases are highly desired biocatalysts owing to their
      ability to catalyse a wide variety of chemically challenging C-H activation
      reactions. The CYP102A subfamily of enzymes are natural catalytically self
      sufficient proteins consisting of a haem and FMN-FAD reductase domain fused in a
      single-component system. They catalyse the oxygenation of saturated and
      unsaturated fatty acids to produce primarily omega-1, omega-2 and omega-3 hydroxy
      acids. These monooxygenases have potential applications in biotechnology;
      however, their substrate range is still limited and there is a continued need to
      add diversity to this class of biocatalysts. Herein, we present the
      characterisation of two new members of this class of enzymes, CYP102A25 (BMar)
      from Bacillus marmarensis and CYP102A26 (PHal) from Pontibacillus halophilus,
      both of which express readily in a recombinant bacterial host. BMar exhibits the
      highest activity toward myristic acid and shows moderate activity towards
      unsaturated fatty acids. PHal exhibits broader activity towards mid-chain
      saturated (C14 -C18 ) and unsaturated fatty acids. Furthermore, PHal shows good
      regioselectivity for the hydroxylation of myristic acid, targeting the omega-2
      position for C-H activation.

PMID- 29219230
TI  - Similar length of colon is removed regardless of localization in right-sided
      colonic cancer surgery.
AB  - BACKGROUND: Colorectal cancers represent a heterogenous group of tumours. While
      left segmental colectomy is an accepted and oncologically safe practice for left
      sided colonic cancer (CC), some authors suggest that limited segmental resection
      of right-sided cancer should be debated in order to preserve length of the
      resected colon. To our knowledge, caecum and ascending CC have not been analysed
      as different groups of tumours. The objective of this study was to assess if,
      retrospectively, surgical treatment of caecal cancer differed from ascending CC.
      METHODS: A review of all consecutive patients with right colonic resection for
      cancer admitted to the University hospital of Grenoble from January 2005 to
      August 2016 was performed. Length of resected colon was compared between caecal
      primary and ascending CC. Other technical and pathological aspects were analysed
      such as minimal invasive surgery and number of harvested lymph nodes from
      anatomic specimens. RESULTS: Among operated patients, tumour was localized pre
      operatively on caecum in 110 cases and on the right ascending colon in 119 cases.
      Pre-operative localization had no effect on resected colon length (mean 24.5 cm,
      24 +/- 10.34 versus 25 cm +/- 7.28, P = 0.95), on the number of harvested lymph
      nodes with a mean of 15 (+/-7.6) nodes in the caecal group versus 15.2 (+/-7.3)
      (P = 0.72). We noticed 15 cases of discordance between pre- and post-operative
      localization (4 versus 11, P = 0.08). CONCLUSION: Length of resected colon does
      not differ depending on localization of tumour in our center.

PMID- 29219231
TI  - Laboratory exercise for studying the morphology of heat-denatured and amyloid
      aggregates of lysozyme by atomic force microscopy.
AB  - To facilitate learning advanced instrumental techniques, essential tools for
      visualizing biomaterials, a simple and versatile laboratory exercise
      demonstrating the use of Atomic Force Microscopy (AFM) in biomedical applications
      was developed. In this experiment, the morphology of heat-denatured and amyloid
      type aggregates formed from a low-cost and well-characterized model protein, hen
      egg white lysozyme (HEWL), are compared. Structural differences between the
      amorphous and ordered particles are quantified using ImageJ for the analysis of
      AFM images as a postlaboratory assignment. The laboratory exercise allows the
      direct observation of changes in the protein structure and helps students to
      understand the operation of AFM, as well as protein folding and misfolding
      related to many physiological and pathological processes. The described protocol
      stands alone, but also fits well into a larger module on protein structure and
      function or microscopic techniques as it can be linked easily to existing
      laboratory exercises on these topics. It can be easily adapted to the upper level
      undergraduate laboratory courses with limited lab hours as well as graduate level
      courses to improve students' research skills. (c) 2017 by The International Union
      of Biochemistry and Molecular Biology, 46(2):162-171, 2018.

PMID- 29219232
TI  - FastFeedback Questions: A new teaching method.
AB  - In Australian Universities, based on a study from 1992 to 2014, the Feedback item
      has been consistently poorly rated by students. In addition, Biochemistry is a
      complex STEM subject which many students find difficult and was considered the
      hardest subject according to a recent study by Antigua medical school in the
      United States. In this work, a new and interactive teaching method, FastFeedback
      Questions (FFQs), has been devised. FFQs are a rapid formative feedback method
      that involves embedding carefully crafted focus questions alongside PowerPoint
      slides (outside the slide field). The PPT is then projected as usual, but not in
      slide show mode, so the areas outside the main slide window are visible to the
      students. Prior to the lecture students receive a version without the answers.
      During the face-to-face lecture, the lecturer goes through the answers in an
      interactive way by requesting that students answer the FFQs, which can be
      verified immediately from the PPT slide. The focus questions not only increase
      students' understanding of the slides, they also model good answers. FFQs were
      delivered to the students of third year clinical biochemistry at Curtin
      University. Number of students in this study, n = 311. The final exam marks
      support the use of FFQs as there is an overall improvement of the student average
      grade by ~10% from ~63% in 2010-2014 (no FFQs) to ~72.6% in 2015-2017 (FFQs).
      FFQs have also gained the accolade of the students as their feedback was on
      average ~97% compared to ~80.5% for the Faculty and University. (c) 2017 by The
      International Union of Biochemistry and Molecular Biology, 46(2):121-129, 2018.

PMID- 29219233
TI  - IPAWS: The International Paramedic Anxiety Wellbeing and Stress study.

PMID- 29219234
TI  - Atypical case of hyaluronidase allergy with orbital compartment syndrome and
      visual loss.

PMID- 29219235
TI  - Catalysis of Carbon Dioxide Photoreduction on Nanosheets: Fundamentals and
      Challenges.
AB  - The transformation of CO2 into fuels and chemicals by photocatalysis is a
      promising strategy to provide a long-term solution to mitigating global warming
      and energy-supply problems. Achievements in photocatalysis during the last decade
      have sparked increased interest in using sunlight to reduce CO2 . Traditional
      semiconductors used in photocatalysis (e.g. TiO2 ) are not suitable for use in
      natural sunlight and their performance is not sufficient even under UV
      irradiation. Some two-dimensional (2D) materials have recently been designed for
      the catalytic reduction of CO2 . These materials still require significant
      modification, which is a challenge when designing a photocatalytic process. An
      overarching aim of this Review is to summarize the literature on the
      photocatalytic conversion of CO2 by various 2D materials in the liquid phase,
      with special attention given to the development of novel 2D photocatalyst
      materials to provide a basis for improved materials.

PMID- 29219236
TI  - A Step Closer to Metal-Free Dinitrogen Activation: A New Chapter in the Chemistry
      of Frustrated Lewis Pairs.
AB  - The end of the metal age: Recent developments in small-molecule activation and
      chemical transformations of main-group species pose the question as to whether
      metal catalysts could be avoided altogether in the activation of dinitrogen. A
      ground-breaking study by Stephan and co-workers clearly implies that the metal
      free activation of N2 with frustrated Lewis pairs may be achievable in the not
      too-distant future.

PMID- 29219237
TI  - The Common Intermediates of Oxygen Evolution and Dissolution Reactions during
      Water Electrolysis on Iridium.
AB  - Understanding the pathways of catalyst degradation during the oxygen evolution
      reaction is a cornerstone in the development of efficient and stable
      electrolyzers, since even for the most promising Ir based anodes the harsh
      reaction conditions are detrimental. The dissolution mechanism is complex and the
      correlation to the oxygen evolution reaction itself is still poorly understood.
      Here, by coupling a scanning flow cell with inductively coupled plasma and online
      electrochemical mass spectrometers, we monitor the oxygen evolution and
      degradation products of Ir and Ir oxides in situ. It is shown that at high anodic
      potentials several dissolution routes become possible, including formation of
      gaseous IrO3 . On the basis of experimental data, possible pathways are proposed
      for the oxygen-evolution-triggered dissolution of Ir and the role of common
      intermediates for these reactions is discussed.

PMID- 29219238
TI  - Coronary balloon catheter tip damage. A bench study of a clinical problem.
AB  - OBJECTIVES: To confirm clinically that coronary balloon catheter tips may be
      damaged during bifurcation treatment with side-branch access through the side of
      a stent. On the bench, we aimed to assess the susceptibility of different balloon
      designs to damage. We compared catheter tip widths. We tested whether balloon tip
      flaring can cause stent distortion. BACKGROUND: We had observed that balloon
      catheters that failed to cross to a side-branch frequently exhibited tip damage.
      METHODS AND RESULTS: We examined microscopically for damage 82 balloon tips after
      clinical side-branch access. In a bench study, the forces required to compress
      catheter tips 0.5 mm were compared to assess susceptibility to damage. We
      compared tip widths of balloons of different nominal inflation diameters. We
      examined stents after side-branch access for distortion. In 42 of 48 (88%) of
      balloon tips from patients with resistance to or failure to cross through the
      side of a stent there was tip damage. Even when the balloon crossed without
      perceptible resistance, tip damage occurred in over half of balloons 18/34 (53%).
      Some balloon designs were more resistant to damage than others. Tips from
      balloons of different nominal diameters from the same manufacturer had the same
      width. Stent distortion caused by damaged balloon tips is improved by kissing
      balloon post-dilatation. CONCLUSIONS: Balloon tip damage is common with crossing
      between stent struts. This is one cause of failure of a balloon to access a side
      branch and a new balloon should be used. If stent distortion is suspected, it
      should be corrected with kissing balloon post-dilatation.

PMID- 29219239
TI  - Few-Layered Black Phosphorus: From Fabrication and Customization to Biomedical
      Applications.
AB  - As a new kind of 2D material, black phosphorus has gained increased attention in
      the past three years. Although few-layered black phosphorus nanosheets (BPs)
      degrade quickly under ambient conditions to phosphate anions, which greatly
      hampers their optical and electronic applications, this property also makes BPs
      highly biocompatible and biodegradable, and is regarded as an advantage for
      various biomedical applications. This Concept summarizes the state-of-art
      progresses of BPs, from fabrication and surface modification to biomedical
      applications. It is expected that BPs with such fascinating properties will
      encourage more scientists to engage in expanding its biomedical applications by
      tackling the scientific challenges involved in their development.

PMID- 29219240
TI  - Comment on "Retinal pulse wave velocity measurement using spectral-domain optical
      coherence tomography".
AB  - This paper comments on the article "Retinal pulse wave velocity measurement using
      spectral-domain optical coherence tomography" by Qian Li et al. The authors
      propose a method to determine the pulse wave velocity in retinal arteries and
      veins. This method should enable a noninvasive determination of biomechanical
      properties of the vessel network, particularly the elasticity of the vessel
      walls. Although the observations the authors made might seem reasonable at first
      glance, they are in fact highly surprising and contradictory to theoretical
      predictions and previously published results.

PMID- 29219241
TI  - Incidental finding of arteria lusoria during transradial coronary
      catheterization: Significance in interventional cardiology.
AB  - Arteria lusoria is the most common anomaly of the aortic arch with an incidence
      of 0.5%-2.5%. It is mostly diagnosed incidentally while performing imaging for
      evaluation of other unrelated medical conditions. The aberrant right subclavian
      artery arises beyond the origin of the left subclavian artery from the aortic
      arch. This results in a complex right-subclavian-aortic anatomy which leads to
      difficulty in transradial coronary angiography. This can lead to prolonged
      procedure time and increased use of catheters by unaware interventionists. This
      is even more important if this is encountered in the setting of an acute
      myocardial infarction. Our review takes into account clinical significance of
      this uncommon anomaly in the field of interventional cardiology.

PMID- 29219242
TI  - Behavioural assessment unit improves outcomes for patients with complex
      psychosocial needs.
AB  - OBJECTIVE: We aimed to assess the impact of a new model of care for patients
      presenting to the ED with acute behavioural disturbance. METHODS: This pre-/post
      intervention study involved creating a dedicated, highly resourced six bed unit,
      the behavioural assessment unit (BAU). Co-located with the ED at the Royal
      Melbourne Hospital, the unit was designed to fast-track the admission of patients
      affected by intoxication, mental illness or psychosocial crisis and provide front
      loaded interventions. RESULTS: In 12 months from 1 April 2016, 2379 patients were
      admitted to the BAU. They were compared with a similar cohort of 3047 patients
      from the entire 2015 ED population. The BAU resulted in a decreased wait to be
      seen (40 min [interquartile range (IQR): 17-86] vs 68 min [IQR: 24-130], P <
      0.001), a decreased wait for a mental health review (117 min [IQR: 49-224] vs 139
      min [IQR: 57-262], P = 0.001) and a decreased ED length of stay (180 min [IQR:
      101-237] vs 328 min [IQR: 227-534], P < 0.001). Patients admitted to the BAU were
      less likely to have a security code (349 (14.7%) vs 538 (17.7%), P = 0.003) and
      less likely to have mechanical restraint (156 episodes (6.6%) vs 275 (9.0%), P <
      0.001) or therapeutic sedation (156 episodes (6.6%) vs 250 (8.2%), P < 0.001).
      CONCLUSION: A unit specifically designed to improve the care of patients
      requiring prolonged ED care due to mental illness and/or intoxication reduces the
      time spent in the ED and the use of some restrictive interventions. We recommend
      this model of care to EDs that care for this complex and challenging group of
      patients.

PMID- 29219243
TI  - Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug
      resistant and rifampicin-resistant tuberculosis in Han Chinese from Hubei
      Province.
AB  - We determined the high-resolution allele and haplotype frequencies at the human
      leucocyte antigen (HLA)A, B and DRB1 loci in the Han population of Hubei
      province, the TB endemic area of Central China, with pulmonary tuberculosis
      (PTB), and established the relationship between HLA-A, B and DRB1 alleles as well
      as haplotypes and susceptibility to multidrug-resistant and rifampicin-resistant
      tuberculosis (MDR/RR-TB). Blood samples were drawn from 174 patients with MDR/RR
      TB and 838 patients with drug-susceptible PTB in ethnic Han population from Hubei
      province (central China). Four-digit allele genotyping of HLA- A, B and DRB1 loci
      was performed using polymerase chain reaction with sequence-specific
      oligonucleotide probes (PCR- SSOP). The allele and haplotype frequencies of HLA
      A, B and DRB1 were determined and compared between patients with MDR/RR-TB and
      patients with drug-susceptible PTB. Statistical analysis of the generated data
      indicated no departure from expectation of Hardy-Weinberg equilibrium (HWE) at
      all loci of the control group. Multivariate analysis identified allele DRB1*08:01
      (p < .0001; OR = 174.5, 95% CI 15.3-1987.2) as independent predictor of MDR/RR
      TB, except for old age (p < .0001; OR = 10. 9, 95% CI 7.6-15.8), previous
      treatment history (p < .0001; OR = 11.0, 95% CI 7.2-16.7) and poor compliance to
      treatment (p < .0001; OR = 12.9, 95% CI 8.4-20.0). While in the subgroup of new
      TB cases, DRB1*08:01 (p < .0001; OR = 80.3, 95% CI 7.0-917.1) and older age (p <
      .0001; OR = 3.9, 95% CI 2.4-6.4) were independent susceptibility factors for
      primary MDR/RR-TB. Our results suggest that a combination of clinical and host
      genetic information about tuberculosis patients may contribute to prediction and
      early detection of MDR/RR-TB.

PMID- 29219244
TI  - "Click" on PLGA-PEG and hyaluronic acid: Gaining access to anti-leishmanial
      pentamidine bioconjugates.
AB  - Pentamidine (Pent), an antiparasitic drug used for the treatment of visceral
      leishmaniasis, has been modified with terminal azide groups and conjugated to two
      different polymer backbones (PLGA-PEG [PP] copolymer and hyaluronic acid [HA])
      armed with alkyne end-groups. The conjugation has been performed by Copper
      Catalyzed Azido Alkyne Cycloaddition (CuAAC) using CuSO4 /sodium ascorbate as
      metal source. The novel PP-Pent and HA-Pent bioconjugates are proposed,
      respectively, as non-targeted and targeted drug delivery systems against
      Leishmania infections. Moreover, Pent has been encapsulated into PP nanoparticles
      by the oil-in-water emulsion method, with the aim to compare the biological
      activity of the bioconjugates with that of the classical drug-loaded delivery
      system that physically entraps the therapeutic agent. Biological assays against
      Leishmania infantum amastigote-infected macrophages and primary macrophages
      revealed that Pent, either covalently conjugated with polymers or loaded into
      polymeric nanoparticles, turned out to be more potent and less toxic than the
      free Pent. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 2778-2785, 2018.

PMID- 29219245
TI  - Behavior profiles of children with autism spectrum disorder in kindergarten:
      Comparison with other developmental disabilities and typically developing
      children.
AB  - : Monitoring behavior patterns that may be specific to autism spectrum disorder
      (ASD) at a population level has the potential to improve the allocation of
      intervention strategies and reduction of the burden of the disease. In Ontario,
      Canada, developmental data are regularly collected for all kindergarten children
      with the Early Development Instrument (EDI), a teacher-completed questionnaire
      that provides information on children's status in five domains: physical, social,
      emotional, language/cognitive, and communication/general knowledge. Our main
      research questions are: (a) are there differences in kindergarten EDI domain
      scores between children who are diagnosed with ASD by Grade 3 and those who
      develop typically or have other disabilities?; (b) do these differences show a
      different pattern in relation to an early (by kindergarten) or late (by Grade 3)
      diagnosis?; and (c) are there specific subdomains on the EDI that demonstrate a
      consistent pattern of differences? EDI domain and subdomain scores were compared
      among groups using multivariate analysis of variance controlling for age, gender,
      EDI year, and EDI year by age interaction. Children with ASD, regardless of
      timing of identification, had significantly lower scores on all domains of the
      EDI than typically developing children. Children with later ASD diagnosis had
      higher scores in kindergarten in cognitive areas but lower scores in social
      emotional areas than children with other disabilities. These findings support the
      potential of the EDI to monitor ASD-like behaviors at the population level.
      Autism Res 2018, 11: 410-420. (c) 2017 International Society for Autism Research,
      Wiley Periodicals, Inc. LAY SUMMARY: Identifying behavior patterns among
      kindergarten children that may be specific to autism spectrum disorder (ASD) at a
      population level has the potential to improve intervention strategies and thus
      reduce the burden of the disease. In Ontario, Canada, developmental data are
      regularly collected with the Early Development Instrument (EDI) for all
      kindergarten children. The behavior in kindergarten of a sub-population of
      children diagnosed with developmental disabilities by age 9 is investigated here
      for patterns that may distinguish children with ASD from those with other
      disorders. Children with later ASD diagnosis had higher scores in kindergarten in
      cognitive areas but lower scores in social-emotional areas than children with
      other disabilities, indicating meaningful differences between those groups even
      before diagnosis. These results support the potential of using the EDI to monitor
      ASD-like behaviors at the population level.

PMID- 29219246
TI  - Identification and genomic characterization of the emerging Senecavirus A in
      southeast China, 2017.
AB  - Senecavirus A (SVA) is an emerging non-enveloped virus with a single-stranded,
      positive-sense RNA genome that belongs to the Senecavirus genus in the
      Picornaviridae family. Senecavirus A-associated swine idiopathic vesicular
      disease and epidemic transient neonatal losses have caused substantial economic
      losses for the swine industry. Here, we describe a case of re-emerging vesicular
      disease among sows and finishing pigs on a swine farm in Fujian Province of
      southeast China. Other causative pathogens, including FMDV, SVDV and VSV, were
      excluded, and a novel SVA strain, CH-FJZZ-2017, was isolated. Sequencing and
      phylogenetic analysis of the complete genome and individual viral proteins
      revealed that CH-FJZZ-2017 is closely related to the US strains in 2015. The
      results further showed that Chinese SVAs have formed two distinct subclades with
      2016 as the turning point. Viruses causing outbreaks after late 2016 shared
      higher nucleotide identities with the US strains in 2015. There is still some
      evolutionary distance between CH-FJZZ-2017 and other strains isolated in late
      2016, suggesting that Chinese SVA isolates have been evolving in different
      directions. This study provides a basis for the development of effective
      prevention and control strategies.

PMID- 29219247
TI  - Diketopyrrolopyrrole-Based and Tetracyano-Bridged Small Molecules for Bulk
      Heterojunction Organic Solar Cells.
AB  - Research on bulk heterojunction organic solar cells has rapidly grown over the
      past two decades, and device performance has reached power conversion
      efficiencies over 13 %. In this focus review, we highlight design strategies used
      for the development of diketopyrrolopyrrole- and tetracyano-based molecular
      donors. We also describe how tetracyano-bridged non-fullerene acceptors can be
      developed by a click-type [2+2]-cycloaddition-electrocyclic ring-opening reaction
      of acetylene-bridged small molecules with tetracyanoethylene by simple
      modification.

PMID- 29219248
TI  - "My mother told me that I should not": a qualitative study exploring the
      restrictions placed on adolescent girls living with HIV in Zambia.
AB  - INTRODUCTION: Adolescent girls in sub-Saharan Africa are disproportionately
      affected by HIV due to a range of social and structural factors. As they
      transition to adulthood, they are recipients of increasing blame for HIV
      infection and 'improper' sex, as well as increasing scrutiny, restrictions and
      surveillance. This study used a qualitative and participatory approach to explore
      the messaging and restrictions imposed on adolescent girls living with HIV in
      Zambia. METHODS: Thirty-four in-depth interviews and four participatory workshops
      were carried out with 24 adolescent girls aged 15 to 19 years old living with HIV
      in Lusaka, Zambia. Key themes explored included experiences living with HIV,
      finding out about HIV status, disclosure, experiences with antiretroviral
      treatment, and support needs. Data were organized, coded and analysed using a
      grounded theory approach to thematic analysis. This analysis uses data on
      participants' experiences of living with HIV and their interactions with their
      parents, guardians and healthcare providers. RESULTS: Family and healthcare
      providers, partly in a quest to protect both the health of adolescent girls
      living with HIV and also to protect them from blaming discourse, imposed
      restrictions on their behaviour around three main topics: don't disclose your HIV
      status, don't have sex, and don't miss your medicines. These restrictions were
      often delivered using tactics of fear, and usually disconnected from other
      options. Participants responded to these messages in several ways, including
      internalizing the messages, changing their behaviour either to comply with or
      resist the restrictions, by remaining silent and anxious when restrictions were
      broken, and developing concerns around their own health and sexual and
      reproductive aspirations. Participants also sometimes experiencing stigma when
      restrictions could not be maintained. CONCLUSIONS: Restrictive messages were
      delivered to adolescent girls living with HIV through the broader social
      discourses of stigma, religion, and global and local narratives about HIV.
      Programmes aiming to support adolescent girls living with HIV need to work
      together with parents and healthcare providers to reflect on the impact of
      sanctioning messages, and to encourage more enabling and empowering messaging for
      adolescent girls living with HIV.

PMID- 29219250
TI  - Response to Fragmented QRS Complex Predicts Contrast-Induced Nephropathy and In
      Hospital Mortality After Primary Percutaneous Coronary Intervention in Patients
      With ST-Segment Elevation Myocardial Infarction.

PMID- 29219249
TI  - Activities of 11-Azaartemisinin and N-Sulfonyl Derivatives against Asexual and
      Transmissible Malaria Parasites.
AB  - Dihydroartemisinin (DHA), either used in its own right or as the active drug
      generated in vivo from the other artemisinins in current clinical use-artemether
      and artesunate-induces quiescence in ring-stage parasites of Plasmodium
      falciparum (Pf). This induction of quiescence is linked to artemisinin
      resistance. Thus, we have turned to structurally disparate artemisinins that are
      incapable of providing DHA on metabolism. Accordingly, 11-azaartemisinin 5 and
      selected N-sulfonyl derivatives were screened against intraerythrocytic asexual
      stages of drug-sensitive Pf NF54 and drug-resistant K1 and W2 parasites. Most
      displayed appreciable activities against all three strains, with IC50 values
      <10.5 nm. The p-trifluoromethylbenzenesulfonyl-11-azaartemisinin derivative 11
      [(4'-trifluoromethyl)benzenesulfonylazaartemisinin] was the most active, with
      IC50 values between 2 and 3 nm. The compounds were screened against Pf NF54 early
      and transmissible late intraerythrocytic-stage gametocytes using luciferase and
      parasite lactate dehydrogenase (pLDH) assays. The 2'-thienylsulfonyl derivative
      16 (2'-thiophenesulfonylazaartemisinin) was notably active against late-stage (IV
      V) gametocytes with an IC50 value of 8.7 nm. All compounds were relatively
      nontoxic to human fetal lung WI-38 fibroblasts, showing selectivity indices of
      >2000 toward asexual parasites. Overall, the readily accessible 11-azaartemisinin
      5 and the sulfonyl derivatives 11 and 16 represent potential candidates for
      further development, in particular for transmission blocking of artemisinin
      resistant parasites.

PMID- 29219251
TI  - An unusual myopericarditis.

PMID- 29219253
TI  - First experience of the usage of a GORE CARDIOFORM Septal Occluder device for
      treatment of a significant residual commissural mitral regurgitation jet
      following a MitraClip procedure.
AB  - : The MitraClip (Abbott Vascular, Santa Clara, CA) procedure has emerged as a
      safe and effective treatment option for treatment of selected patients with
      severe mitral regurgitation (MR) who are at high risk for surgery. Effective
      reduction of MR is important to ensure an optimal clinical outcome. We present
      here the first case report of a significant commissural leak after a MitraClip
      procedure treated with a GORE CARDIOFORM Septal Occluder device (WL Gore &
      Associates, Flagstaff, AZ). CASE REPORT: An 81-year-old male presented with
      symptomatic recurrent MR following a MitraClip procedure using two clips. After
      adding another clip, there was still a residual jet medially. We plugged the gap
      using 12-mm AMPLATZER Muscular VSD Occluder device (St. Jude Medical,
      Minneapolis, MN). MR was reduced but hemolysis occurred. We retrieved the VSD
      Occluder device to improve hemolysis, but the MR jet worsened to severe, so we
      placed a 30-mm GORE CARDIOFORM Septal Occluder device. The device was stable, the
      MR jet was reduced dramatically, and hemolysis was not observed. Materials of
      these devices are mesh fabric made from nitinol and polyester in a VSD Occluder
      device and expanded polytetrafluoroethylene in GORE CARDIOFORM Septal Occluder
      device. The difference between device materials affects flow pattern of residual
      jet and hemolysis. In conclusion, the patient's risk for hemolysis is potentially
      affected by the occluder or plug material. GORE CARDIOFORM is a feasible choice
      to reduce the risk of hemolysis in a selected patient.

PMID- 29219254
TI  - Primary bilateral uveal melanoma: a population-based study and systematic review.
AB  - IMPORTANCE: Primary bilateral uveal melanoma (UM) is a rare and incompletely
      described entity. It is not known how these patients compare to those with
      unilateral UM. BACKGROUND: We sought to comprehensively characterize and compare
      patients with primary bilateral and unilateral UM. DESIGN: Retrospective,
      population-based and systematic review. PARTICIPANTS: Patients with bilateral (n
      = 52) and unilateral UM (n = 8915). METHODS: We analysed cases of primary
      bilateral UM from three data sources: (i) the University Hospitals Cleveland
      Medical Center pathology database from 1996 to 2016 (n = 1); (ii) the
      Surveillance, Epidemiology and End-Results (SEER)-18 database from 1973 to 2013
      (n = 5) and (iii) a systematic review of the English language literature (n =
      46). Cases of unilateral UM were obtained from the SEER-18 database from 1973 to
      2013 for comparison (n = 8915). MAIN OUTCOME MEASURES: Demographics,
      clinicopathological characteristics, treatments and survival. RESULTS: There were
      no differences in sex, race, mean age at diagnosis, site of uveal involvement,
      metastases at diagnosis, or treatment among patients with bilateral as compared
      to unilateral UM. Additionally, there were no clinicopathological differences
      between the two UMs in each patient with bilateral disease. Overall survival did
      not differ between unilateral and bilateral UM patients, or between bilateral UM
      patients who presented with, or subsequently developed, bilateral disease.
      CONCLUSIONS AND RELEVANCE: Bilateral and unilateral UM patients share similar
      demographics, clinicopathological characteristics, treatments and prognoses.
      Moreover, the development of bilateral disease does not portend a poorer
      prognosis and patients should be treated similarly to those with unilateral
      disease.

PMID- 29219255
TI  - Palladium-Catalyzed Intramolecular Trost-Oppolzer-Type Alder-Ene Reaction of
      Dienyl Acetates to Cyclopentadienes.
AB  - A new approach to the synthesis of highly substituted cyclopentadienes, indenes,
      and cyclopentene-fused heteroarenes by means of the Pd-catalyzed Trost-Oppolzer
      type intramolecular Alder-ene reaction of 2,4-pentadienyl acetates is described.
      This unprecedented transformation combines the electrophilic features of the
      Tsuji-Trost reaction with the nucleophilic features of the Alder-ene reaction.
      The overall outcome can be perceived as a hitherto unknown "acid-free" iso
      Nazarov-type cyclization. The versatility of this strategy was further
      demonstrated by the formal synthesis of paucifloral F, a resveratrol-based
      natural product.

PMID- 29219256
TI  - Single-shot speckle correlation fluorescence microscopy in thick scattering
      tissue with image reconstruction priors.
AB  - Deep tissue imaging in the multiple scattering regime remains at the frontier of
      fluorescence microscopy. Speckle correlation imaging (SCI) can computationally
      uncover objects hidden behind a scattering layer, but has only been demonstrated
      with scattered laser illumination and in geometries where the scatterer is in the
      far field of the target object. Here, SCI is extended to imaging a planar
      fluorescent signal at the back surface of a 500-MUm-thick slice of mouse brain.
      The object is reconstructed from a single snapshot through phase retrieval using
      a proximal algorithm that easily incorporates image priors. Simulations and
      experiments demonstrate improved image recovery with this approach compared to
      the conventional SCI algorithm.

PMID- 29219257
TI  - Evaluation of a mental health liaison team. Part 2: the themes and their effect
      on practice.
AB  - Hospitals and emergency departments (EDs) are caring for increasing numbers of
      patients who present with underlying mental health issues. Managing these
      patients can be challenging for clinical staff who often lack the specialist
      knowledge and skills required to provide appropriate care. This article, part two
      of two on the evaluation of a newly formed mental health liaison team (MHLT)
      working in a general hospital, focuses on the perceptions and experiences of the
      MHLT participants, and explores three sub-themes derived from the interview data.
      The article considers the effect of these themes on practice, and the
      relationship between MHLT members and staff in EDs and the wider hospital.

PMID- 29219258
TI  - Military preceptees' journey in the emergency department.
AB  - This article is an account of the experiences of two newly qualified military
      graduates who became preceptees in an emergency department (ED). It considers the
      emotions felt, the benefits of previous nursing experience, and the importance of
      reflection and support from colleagues. The article also suggests that ED
      experience can shape nurses' ability to undertake operational and non-operational
      military nursing roles.

PMID- 29219259
TI  - Nursing management of childhood chickenpox infection.
AB  - Chickenpox is an extremely contagious infectious disease caused by varicella
      zoster virus (VZV). It is a common childhood illness characterised by an itchy
      vesicular rash and fever, which usually resolves spontaneously without medical
      intervention. Serious, and rarely fatal, complications can occur, including
      pneumonia, central nervous system infection, overwhelming secondary bacterial
      infections, especially with Group A streptococcus, and necrotising fasciitis.
      Therefore it is crucial that emergency department (ED) nurses can recognise the
      signs and symptoms that indicate deterioration. This article reviews best
      practice management of children with chickenpox, gives up-to-date guidance on the
      safe use of antipyretics, the avoidance of ibuprofen and discusses immunisation
      against VZV. It also includes implications for nursing practice and a case study
      that illustrates some of the challenges that ED nurses may encounter.

PMID- 29219260
TI  - [Gene Analysis for the Sudden Death of Hypertrophic Cardiomyopathy by Whole Exome
      Sequencing.]
AB  - OBJECTIVES: To analyze the related pathogenicity gene mutations in a sudden death
      of hypertrophic cardiomyopathy (HCM) on whole exome level. METHODS: Whole exome
      sequencing (WES) was been performed on a sudden death case sample with
      pathological features of HCM by Illumina(r) Hiseq 2500 platform. Using hg19 as
      the reference sequences, the sequencing data were analyzed. Suspicious single
      nucleotide variants (SNV) were screened, and the conservatism and function were
      analyzed by the software such as PhyloP, PolyPhen-2, SIFT, etc. RESULTS: After
      screening, a heterozygous mutation C719R was finally identified in the gene
      MYBPC3 of this case. CONCLUSIONS: The molecular anatomy on whole exome level by
      second generation sequencing technology can help to define the molecular
      mechanism of HCM and provide a new mothed and thought for analysis of death
      cause.

PMID- 29219261
TI  - [Relationship between Wound Age and the Expression of Fzd2 in Rats Skeletal
      Muscle after Contusion].
AB  - OBJECTIVES: To investigate the relationship between wound age and the expressions
      of frizzled-2 (Fzd2) mRNA and its protein in rats skeletal muscle after
      contusion, and to explore its possibility of being an index for wound age
      estimation. METHODS: The mRNA and protein expressions of Fzd2 in rats skeletal
      muscle of the control group and the experimental group within 4-48 h after
      contusion were detected per 4 h by RT-qPCR and Western blotting. RESULTS: AThe
      relative expression of Fzd2 mRNA increased at 24 h, 36 h and 40 h after
      contusion, and the expression at 24 h was twice as the control group ( P<0.05).
      The relative expression of Fzd2 protein changed inconspicuously after contusion
      (P>0.05). CONCLUSIONS: The changes of Fzd2 mRNA expression after contusion in a
      certain time can be a basis to estimate wound age by combined multi-indicators.

PMID- 29219262
TI  - [Screening of Differential Expression Proteins in Rat Brain Tissues after DAI by
      iTRAQ-LC-MS/MS].
AB  - OBJECTIVES: To screen for the differential expression proteins in brain tissues
      of SD rat after diffuse axonal injury (DAI) by isobaric tag for relative and
      absolute quantification-liquid chromatograph-mass spectrometer/mass spectrometer
      (iTRAQ-LC-MS/MS), and to explore potential biomarkers available for the diagnosis
      of DAI. METHODS: Animal models of DAI were established with the Marmarou method
      as reference, and the subjects were divided into blank control group (n=4), sham
      strike group (n=4) and fatal strike group (n=4), respectively. The proteins in
      rat brain tissues were detected by iTRAQ-LC-MS/MS, and bioinformatics analysis
      and verification were performed on the results and screened for the differential
      expression proteins. RESULTS: A total of 2 016 proteins were identified and
      quantified. The bioinformatics analysis revealed that the proteins had wide
      distribution and function, and participated in different biological processes.
      There were 16 proteins showed differential expression in fatal strike group,
      including one up-regulated expression protein and 15 down-regulated expression
      proteins. The results of iTRAQ-LC-MS/MS were confirmed by Western blotting
      method. CONCLUSIONS: Multiple differential expression proteins in rat brain
      tissues after DAI can be screened by iTRAQ-LC-MS/MS. This not only indicates a
      research direction for exploring the pathogenesis of DAI, but also provides
      potential biomarkers available for the diagnosis of DAI.

PMID- 29219263
TI  - [Comparison of Measurement Methods of Exophthalmos and Its Forensic
      Significance].
AB  - OBJECTIVES: To compare the differences between Hertel exophthalmometry and CT on
      exophthalmos measurement, and explore its practical application value in forensic
      medicine. METHODS: Fifty-six normal individuals without eye injuries or diseases
      were selected as the control group. The absolute values of exophthalmos were
      measured in the standardized CT image workstation. The difference of binocular
      exophthalmos was compared in normal group. Forty-seven cases with unilateral
      orbital fracture were divided into injured eye group and normal eye group
      according to the presence of binocular orbital fractures. The differences of the
      absolute values of eophthalmos from the same eye and the relative values of
      eophthalmos between two eyes for same person measured by Hertel exophthalmometry
      and CT were analyzed. RESULTS: There was no statistical difference of
      exophthalmos between the normal eyes measured by CT method. In the normal eye
      group, the absolute value of exophthalmos measured by CT method was (16.66+/
      5.41) mm, which was (16.16+/-4.45) mm when measured by the Hertel
      exophthalmometry method. There was no statistical difference between two groups
      (P>0.05). In the injured eye group, there was statistical difference between the
      absolute values of exophthalmos measured by two measurement methods ( P<0.05).
      There was no statistical difference of the relative values of exophthalmos
      between the injured eyes and the normal eyes by two measurement methods (P>0.05).
      CONCLUSIONS: CT method has a good consistency with Hertel exophthalmometry, which
      can be applied into the practice of medicolegal expertise.

PMID- 29219264
TI  - [Identification of Y-chromosomal Genetic Types for the Soldier's Remains from
      Huaihai Campaign].
AB  - OBJECTIVES: To identify the Y-chromosomal genetic types for the soldier's remains
      from Huaihai Campaign, and to offer a clue for search of their paternal
      relatives. METHODS: DNA of the remains were extracted by the ancient DNA
      extraction method. Yfiler kit was used for the multiplex amplification of 17 Y
      STR loci. The haplogroups of the samples were speculated. Detailed genotyping of
      the selected Y-SNP was performed based on the latest Y-chromosome phylogenetic
      tree. Haplotype-sharing analysis was done based on the data of Y-SNP and Y-STR,
      the closest modern individual information to the genetic relationship of remains
      was gained. RESULTS: A total of 8 Y-STR haplotypes were observed on 17 Y-STR loci
      of 8 male individuals. Furthermore, 6 Y-SNP haplogroups were identified, which
      were O2a1-M95+, O1a1-P203+, O3*-M122+/M234-, D1-M15+, C3*-ST and R1a1-M17+.
      CONCLUSIONS: Identification of Y-chromosomal genetic types for the soldier's
      remains from Huaihai Campaign shows a reference value on inferring the
      geographical origins of old materials.

PMID- 29219265
TI  - [Formula Derivation and Validation of Probability of Exclusion in the Cases of
      Standard Triplet Parentage Testing].
AB  - OBJECTIVES: To derive and experiment validate the probability of exclusion (PE)
      formulas in the cases of standard triplet parentage testing. METHODS: The
      formulas were derived voluntarily based on the PE definition: [Formula: see
      text]. This formula was compared with the 5 formulas (1)-(5) reported previously,
      and the PE values of 19 autosomal STR loci in AGCU EX20 system were calculated.
      Based on 1 000 samples of single-parentage cases and 1 000 unrelated individuals,
      the real experiment was designed and the real experiment results of PE were
      calculated. Ten million pairs of simulated biological mother and son and 10
      million random individuals were gained by random simulation method, and the
      simulated experiment was designed and the simulated values of PE were calculated.
      In 19 STR loci, the sum of all allele frequency (S) was calculated, and the
      formula values of PE were compared with the values of real and simulated
      experiments. RESULTS: If S=1, the calculation values of formula (1), (2), (5) and
      (6) were quite the same, which accord with the double verification of real and
      simulated experiments. If S?1, there was a minor error in the calculation results
      of formula (1), (2), (5) and (6), while which had a large error in formula (3)
      and (4). CONCLUSIONS: The formula (6) derived in present study and the classical
      formulas (1), (2) and (5) can be applied to the standard triplet parentage
      testing. The S value has a certain influence on PE calculation.

PMID- 29219266
TI  - [Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGMTM Platform].
AB  - OBJECTIVES: To analyze and detect the whole genome sequence of human
      mitochondrial DNA (mtDNA) by Ion Torrent PGMTM platform and to study the
      differences of mtDNA sequence in different tissues. METHODS: Samples were
      collected from 6 unrelated individuals by forensic postmortem examination,
      including chest blood, hair, costicartilage, nail, skeletal muscle and oral
      epithelium. Amplification of whole genome sequence of mtDNA was performed by 4
      pairs of primer. Libraries were constructed with Ion ShearTM Plus Reagents kit
      and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed
      using Ion Torrent PGMTM platform. Sanger sequencing was used to determine the
      heteroplasmy positions and the mutation positions on HVI region. RESULTS: The
      whole genome sequence of mtDNA from all samples were amplified successfully. Six
      unrelated individuals belonged to 6 different haplotypes. Different tissues in
      one individual had heteroplasmy difference. The heteroplasmy positions and the
      mutation positions on HVI region were verified by Sanger sequencing. After a
      consistency check by the Kappa method, it was found that the results of mtDNA
      sequence had a high consistency in different tissues. CONCLUSIONS: The testing
      method used in present study for sequencing the whole genome sequence of human
      mtDNA can detect the heteroplasmy difference in different tissues, which have
      good consistency. The results provide guidance for the further applications of
      mtDNA in forensic science.

PMID- 29219267
TI  - [Forensic Analysis for 54 Cases of Suxamethonium Chloride Poisoning].
AB  - OBJECTIVES: To observe and analyze the performance of forensic science in the
      cases of suxa- methonium chloride poisoning, and to improve the identification of
      suxamethonium chloride poisoning. METHODS: Fifty-four cases of suxamethonium
      chloride poisoning were collected. The rules of determination of suxamethonium
      chloride poisoning were observed by the retrospective analysis of pathological
      and toxicological changes as well as case features. RESULTS: The pathological
      features of suxamethonium chloride poisoning were similar to the general changes
      of sudden death, which mainly included acute pulmonary congestion and edema, and
      partly showed myocardial disarray and fracture. Suxamethonium chloride could be
      detected in the heart blood of all cases and in skin tissue of part cases.
      CONCLUSIONS: Suxa-methonium chloride poisoning has the characteristics with fast
      death and covert means, which are difficult to rescue and easily miss inspection.
      For the cases of sudden death or suspicious death, determination of suxamethonium
      chloride should be taken as a routine detection index to prevent missing
      inspection.

PMID- 29219268
TI  - [Application of Susceptibility Weighted Imaging in the Identification of
      Hemorrhagic Diffuse Axonal Injury].
AB  - OBJECTIVES: To explore the application value of susceptibility weighted imaging
      (SWI) in the forensic identification of hemorrhagic diffuse axonal injury (DAI).
      METHODS: The forensic identification materials of 20 DAI cases were analyzed
      retrospectively. The sequence image materials of T1WI, T2WI, diffusion weighted
      imaging (DWI), fluid attenuated inversion recovery (FLAIR) and susceptibility
      weighted imaging (SWI) were analyzed statistically. RESULTS: DAI related
      hemorrhage focus commonly located in the superficial area of brain. The detection
      rate of hemorrhage focus by SWI was the highest, which showing significant
      difference (P<0.05) compared with other sequence images. CONCLUSIONS: The SWI
      plays an important role in the forensic identification of DAI.

PMID- 29219269
TI  - [DNA Extraction from Old Bones by AutoMate ExpressTM System].
AB  - OBJECTIVES: To establish a method for extracting DNA from old bones by AutoMate
      ExpressTM system. METHODS: Bones were grinded into powder by freeze-mill. After
      extraction by AutoMate ExpressTM, DNA were amplified and genotyped by
      Identifiler(r)Plus and MinFilerTM kits. RESULTS: DNA were extracted from 10 old
      bone samples, which kept in different environments with the postmortem interval
      from 10 to 20 years, in 3 hours by AutoMate ExpressTM system. Complete STR typing
      results were obtained from 8 samples. CONCLUSIONS: AutoMate ExpressTM system can
      quickly and efficiently extract DNA from old bones, which can be applied in
      forensic practice.

PMID- 29219270
TI  - [Genetic Polymorphisms of 17 Y-STR Loci in Nantong Han Population].
AB  - OBJECTIVES: To analyze the genetic phenotypes of Nantong Han population and
      evaluate the application value of 17 Y-STR loci in Nantong population. METHODS:
      The peripheral blood samples were collected from 343 unrelated Nantong Han males
      and the genomic DNA were extracted by Chelex-100 method. Genotyping was performed
      using the AmpFlSTR YfilerTM Kit. The results were compared with other 12 Han
      populations, including Anhui, Jiangsu, Jiangxi, Shandong, Shanghai, Zhejiang (1),
      Lanzhou, Nanyang, Luzhou, Mudanjiang, Shanxi and Zhejiang (2), and 9 minority
      populations (Mongol, Xibe, Tibetan in Lhasa, Tibetan in Qinghai, Kazak, Uighur,
      Manchu, Paiwan in Taiwan and Tujia). RESULTS: A total of 327 different haplotypes
      were found in 17 Y-STR loci in Nantong Han population. The haplotype diversity
      (HD) was 0.999 7. The Rst value between Nantong Han and other Chinese populations
      ranged from -0.000 6 to 0.263 5. The multidimensional scaling results showed that
      Nantong Han population had no significant differences between most of the Han
      populations, but had significant differences between most of Chinese minority
      populations. CONCLUSIONS: Seventeen Y-STR loci can be a powerful tool for
      forensic application because of its high polymorphism in Nantong Han population.

PMID- 29219271
TI  - [Polymorphisms of 19 STR Loci in Guizhou Han Population and Their Forensic
      Application].
AB  - OBJECTIVES: To investigate the allelic distribution of 19 autosomal STR loci in
      Guizhou Han population, and to estimate the forensic application value. METHODS:
      The 19 autosomal STR loci in 520 unrelated healthy individuals from Guizhou Han
      population were studied using GoldeneyeTM 20A kit. The 310 genetic analyzer was
      used for capillary electrophoresis, and the GeneMapper(r)ID v3.1 for genotyping.
      RESULTS: The heterozygosis, the discrimination power, the probability of
      exclusion, the polymorphism information content, the cumulative discrimination
      power and the cumulative probability of exclusion of the 19 STR loci were 0.603 8
      0.916 4, 0.790 0-0.985 6, 0.295 5-0.826 9, 0.553 5-0.908 9, 1-1.230 0*10-22 and
      0.999 999 99, respectively. Compared with other five Han populations in pairwise
      allelic frequencies, Guizhou Han only had significant differences with Shandong
      Han, Liaoning Han and Shanxi Han. CONCLUSIONS: The 19 autosomal STR loci such as
      D19S433 have a highly genetic polymorphic in Guizhou Han population, which have
      application values in the researches of population genetics and forensic
      genetics.

PMID- 29219272
TI  - [Application of IMA and H-FABP in Forensic Diagnosis of Sudden Cardiac Death].
AB  - Acute myocardial ischemia is the most common cause of sudden cardiac death. The
      diagnosis of early myocardial ischemia is a hot point in forensic medicine, which
      is also an early and important part for a prevention against myocardial
      infarction. This paper conducts a comprehensive discussion of the structure,
      function, clinical value and forensic medicine application prospect of ischemia
      modified albumin (IMA) and heart-type fatty acid binding protein (H-FABP), aiming
      to determine whether the two proteins can be used as biochemical detection
      indicators of early myocardial ischemia for the diagnosis of sudden cardiac death
      in forensic medicine.

PMID- 29219273
TI  - [Application of Metagenomics in Forensic Identification].
AB  - With the development of molecular biology and genomics, metagenomics is playing a
      more important role in forensic science and forensic identification. In recent
      years, as a branch discipline studying the composition profile and diversity of
      microbe flora as well as studying the interaction within microbe and with
      environment, the application of metagenomics has gradually risen and brought new
      opportunities for forensic identification-related area. In this review, strategy
      of metagenomics and its application in forensic identification including
      individual identification, origin determination of biological stain in crime
      scene and drug abuse detection are summarized. This article aims to elucidate the
      role and application value of metagenomics in forensic science.

PMID- 29219274
TI  - Bilateral testicular torsion in an adolescent: a case with challenging diagnosis.
AB  - Bilateral testicular torsion is a very uncommon emergency, with a challenging
      differential diagnosis. We describe the case of a 15-year-old patient with a left
      testicular torsion of 48 hours of duration and a sudden onset of right scrotum
      pain during his stay at the emergency area. Bilateral testicular torsion was
      diagnosed after repeat physical examination and doppler ultrasound, which had
      been normal for right testis in a first evaluation. Surgical exploration was
      performed with orchiectomy in left testis and fixation in right testis. In
      previous literature, there are reported bilateral torsion only in four
      adolescents and five adults. With this case, we demonstrate that bilateral
      spermatic cord torsion may be easily overlooked in a patient with acute scrotum
      and we emphasize the importance of bilateral exploration in testicular torsion.

PMID- 29219275
TI  - Synchronous abdominal tumors: is combined laparoscopic surgery in a single
      approach a safe option?
AB  - BACKGROUND AND PURPOSE: Recent advances in cancer treatment have resulted in
      better prognosis with impact on patient's survival, allowing an increase in
      incidence of a second primary neoplasm. The development of minimally invasive
      surgery has provided similar outcomes in comparison to open surgery with
      potentially less morbidity. Consequently, this technique has been used as a safe
      option to simultaneously treat synchronous abdominal malignancies during a single
      operating room visit. The objective of this study is to describe the experience
      of two tertiary cancer hospitals in Brazil, in the minimally invasive treatment
      of synchronous abdominal neoplasms and to evaluate its feasibility and peri
      operative results. MATERIALS AND METHODS: We retrospectively reviewed the data
      from patients who were submitted to combined laparoscopic procedures performed in
      two tertiary hospitals in Brazil from May 2009 to February 2015. RESULTS: A total
      of 12 patients (9 males and 3 females) with a mean age of 58.83 years (range: 33
      to 76 years) underwent combined laparoscopic surgeries for the treatment of at
      least one urological disease. The total average duration of surgery was 339.8
      minutes (range: 210 to 480 min). The average amount of intraoperative bleeding
      was 276.6mL (range: 70 to 550mL) and length of hospitalization was 5.08 days
      (range: 3 to 10 days). Two patients suffered minor complications regarding
      Clavien system during the immediate postoperative period. CONCLUSIONS: Combined
      laparoscopic surgery for the treatment of synchronous tumors is feasible, viable
      and safe. In our study, there was a low risk of postoperative morbidity.

PMID- 29219276
TI  - Endourologic strategies for a minimally invasive management of urinary tract
      stones in patients with urinary diversion.
AB  - OBJECTIVE: To present our experience in minimally invasive management of urinary
      tract stones in patients with urinary diversion. MATERIALS AND METHODS: We
      retrospectively reviewed 26 patients with urinary tract stones after cystectomy
      and urinary diversion. The types of urinary diversion were ileal conduit, colon
      conduit, ileal orthotopic neobladder in 19, 4, and 3 patients, respectively. At
      postoperative days 2, a plain KUB and urinary ultrasonography were performed in
      order to assess stone fragmentation or hydronephrosis. According to postoperative
      imaging, stone free rate (SFR) was defined as complete absence of fragments or
      residual stones less than 4mm. RESULTS: 19 patients were treated with minimally
      invasive percutaneous lithotripsy (MPCNL) and 2 patients required second-look
      MPCNL. Anterograde flexible ureteroscopy was performed in 2 patients, while in 2
      patients a combined anterograde and retrograde approach was required. Three
      reservoir stones were treated by transurethral neo-bladder lithotripsy.
      Postoperative significant complications occurred in 2 patients (7.7%). The
      highest percentage of stone composition was struvite, as a result of chronic
      urinary tract infection (UTI). SFR was 88.5% (23 of 26). CONCLUSIONS: Our
      experience showed that MPCNL is a safe and effective treatment modality with
      little morbidity for renal and upper ureteral stones in patients with urinary
      diversion. For middle and lower ureteral stones, an anterograde approach could be
      also considered as a first line treatment, but a combined anterograde and
      retrograde approach was required when the anterograde access alone cannot provide
      acceptable results.

PMID- 29219277
TI  - Prostate cancer incidentally discovered at the time of radical cystoprostatectomy
      does not decrease overall survival: Results from a large Chinese medical center.
AB  - PURPOSE: To investigate the incidence and pathologic characteristics of prostate
      cancer (PCa) incidentally discovered at the time of radical cystectomy and its
      impact on overall survival. MATERIALS AND METHODS: A single center retrospective
      study of 762 male patients who underwent radical cystoprostatectomy from Jan 1994
      to Dec 2012. RESULTS: Of all included patients, 132 (17.3%) were found to have
      PCa. Patients with incidental PCa had a significantly higher mean age (69.2 vs.
      62.2 years, P=0.015). Among the 132 patients with PCa, prostate specific antigen
      (PSA) analysis was available in 76 patients (57.6%), with a median value of
      1.06ng/mL, and 61 (80.3%) patients had a PSA value below 4ng/mL. Four hundred and
      thirty-six patients (57.1%) were successfully followed, with a median duration of
      46.5 months. The overall 5-year survival rate was 62.1%, and the 5-year cancer
      specific survival rate was 72%. PCa recurrence was defined by two consecutive PSA
      values of >0.2 ng/mL and rising, and no PCa recurrence occurred. According to a
      univariate analyses, incidental PCa was not associated with cancer-specific
      survival (P=0.192) or overall survival (P=0.493). According to univariate
      analyses, the overall survival of patients with PCa was not associated with
      prostate cancer staging, PSA value, or Gleason score (All P values>0.05).
      CONCLUSIONS: Prostate cancer incidentally discovered at the time of radical
      cystectomy does not decrease overall survival. Patients with incidental PCa were
      older than those without. The PSA value before operation is not helpful for
      predicting incidental prostate cancers.

PMID- 29219278
TI  - Clinical features of carriers of reciprocal chromosomal translocations involving
      chromosome 2: report of nine cases and review of the literature.
AB  - OBJECTIVE: To explore the clinical features of carriers of chromosome 2
      translocations, enabling informed genetic counseling of these patients. MATERIALS
      AND METHODS: Eighty-two male carriers of a translocation who were infertile or
      receiving fertility counseling were recruited. Cytogenetic analyses were
      performed using G-banding. A search of PubMed was performed to determine whether
      the identified translocations on chromosome 2 are involved in male infertility.
      The relationships of translocation breakpoints with male infertility and
      recurrent pregnancy loss were analyzed. RESULTS: Of the 82 translocation
      carriers, 9 (11%) were carriers of a chromosome 2 translocation. Four cases had
      oligozoospermia or infertility, while five had normal semen. In an analysis of
      the literature, 55 patients who were carriers of chromosome 2 translocations were
      also reviewed. Breakpoints at 2p13 and 2q31 were observed in six patients each,
      and were the most common. Breakpoints at 2p23, 2p13, 2p11.2, 2q31, and 2q37 were
      associated to both pre-gestational and gestational infertility, while other
      breakpoints were associated with gestational infertility. CONCLUSIONS: All
      breakpoints at chromosome 2 were correlated with gestational infertility.
      Carriers of chromosome 2 translocations should therefore receive counseling to
      continue with natural conception and use of different technologies available via
      assisted reproductive technology, such as preimplantation genetic diagnosis.

PMID- 29219279
TI  - Use of photodynamic inactivation for in vitro reduction of prevalent bacteria in
      Fournier's Gangrene.
AB  - Fournier's Gangrene (FG) is an infectious disease caused by several synergic
      microbes, with high morbidity and mortality rates; therefore, the search for new
      less invasive and mutilating treatments, with faster recovery, has been proposed.
      Surgical intervention, the use of several systemic and topic antibiotics, and
      hyperbaric oxygen therapy are currently the best approach for the treatment of
      these patients. The use of Photodynamic Inactivation (PDI) aims to lower
      morbidity and mortality, by reducing bacterial microbiota and speeding wound
      healing. In the present study, viable bacteria were separated in four groups:
      Group L-/F- (no irradiation with red laser and absence of methylene blue
      photosensitizer), Group L-/F+ (no irradiation with red laser and presence of
      methylene blue), Group L+/F- (irradiation with red laser and absence of methylene
      blue) and L+/F+ (irradiation with red laser associated to methylene blue). In all
      groups, exposure time to treatment was 5, 10 and 15 minutes. The concentration of
      methylene blue photosensitizer was 0.1mg/L, and the dose of red laser (660nm wave
      length) was 176.9mW/cm2. Following irradiation, the reduction of number of
      bacteria was evaluated, and the results were expressed in colony forming units
      (CFU) and as exponential reduction. As the main results, in the L+/F+ group,
      there were no Clostridium perfringens and Staphylococcus aureus CFUs and there
      was a reduction of Escherichia coli that was not observed in the other groups.

PMID- 29219280
TI  - Transperitoneal vs. extraperitoneal radical cystectomy for bladder cancer: A
      retrospective study.
AB  - PURPOSE: Conventional transperitoneal radical cystectomy (TPRC) is the standard
      approach for muscle invasive bladder cancer. But, the procedure is associated
      with significant morbidities like urinary leak, ileus, and infection. To reduce
      these morbidities, the technique of extraperitoneal radical cystectomy (EPRC) was
      described by us in 1999. We compared these two approaches and the data accrued
      forms the basis of this report. MATERIALS AND METHODS: All patients who underwent
      radical cystectomy for bladder cancer by the author (JNK) with follow-up for at
      least 5 years were included. A total of 338 patients were studied, with 180
      patients in EPRC group and 158 in TPRC group. RESULTS: There were 3 mortalities
      within 30 days in TPRC group and one in EPRC group. Early complication rate was
      52% and 58% in EPRC and TPRC groups. Urinary leak occurred in 31 (9.2%) patients
      (13 in EPRC, 18 in TPRC, p=0.19). Gastrointestinal complications like ileus
      occurred in 9 (5%) patients in EPRC group and in 25 (15.8%) patients in TPRC
      group, (p<0.001). Wound dehiscence occurred in 29, and 36 patients in EPRC and
      TPRC groups respectively. The reoperation rate was 6.1% and 12% in EPRC and TPRC
      groups, (p=0.08). Intestinal obstruction were significantly less in EPRC group
      (1.7% vs. 7.8% in TPRC group, p=0.002). Uretero-enteric anastomosis stricture was
      seen in 10 patients (4 in EPRC, 6 in TPRC, p=0.39). CONCLUSIONS: The EPRC is
      associated with decrease gastrointestinal complications, ease of management of
      urinary leaks, and low reoperation rates. Thus EPRC appears safe functionally and
      oncologically.

PMID- 29219281
TI  - Impact on sexual function of surgical treatment in rectal cancer.
AB  - INTRODUCTION: The development of new surgical techniques and medical devices,
      like therapeutical multimodal approaches has allowed for better outcomes on
      patients with rectal cancer (RCa). Owing to that, an increased awareness and
      investment towards better outcomes regarding patients' sexual and urinary
      function has been recently observed. AIM: Evaluate and characterize the sexual
      dysfunction of patients submitted to surgical treatment for RCa. MATERIALS AND
      METHODS: An observational retrospective study including all male patients who
      underwent a surgical treatment for RCa between January 2011 December 2014 (n=43)
      was performed, complemented with an inquiry questionnaire to every patient about
      its sexual habits and level of function before and after surgery. DISCUSSION: All
      patients were male, with an average of 64yo. (range 42-83yo.). The surgical
      procedure was a rectum anterior resection (RAR) in 22 patients (56%) and an
      abdominoperineal resection (APR) in 19(44%). Sixty three percent described their
      sexual life as important/very important. Sexual function worsening was observed
      in 76% (65% with complains on erectile function, and 27% on ejaculation).
      Fourteen patients (38%) didn't resume sexual activity after surgery. Increased
      age (p=0.007), surgery performed (APR) (p=0.03) and the presence of a stoma
      (p=0.03) were predictors of ED after surgery. A secondary analysis found that the
      type of surgery (APR) (p=0.04), lower third tumor's location (p=0.03) and
      presence of comorbidities (p=0.013) (namely, smokers and diabetic patients) were
      predictors of de novo ED after surgery. CONCLUSIONS: This study demonstrated the
      clear negative impact in sexual function of patients submitted to a surgical
      treatment for RCa. Since it is a valued feature for patients, it becomes
      essential to correctly evaluate/identify these cases in order to offer an
      adequate therapeutical option.

PMID- 29219282
TI  - Validation of the urgency questionnaire in Portuguese: A new instrument to assess
      overactive bladder syndrome.
AB  - PURPOSE: Overactive Bladder (OAB) is a clinical condition characterized by
      symptoms reported by patients. Therefore, measurement instruments based on
      reported information are important for understanding its impact and treatment
      benefits. The aim of this study was to translate, culturally adapt and validate
      the Urgency Questionnaire (UQ) in Portuguese. MATERIALS AND METHODS: Initially,
      the UQ was translated and culturally adapted to Portuguese. Sixty-three
      volunteers were enrolled in the study and were interviewed for responding the
      Portuguese version of the UQ and the validated Portuguese version of the
      Overactive Bladder Questionnaire short-form (OABq-SF), used as the gold standard
      measurement for the validation process. Psychometric properties such as criterion
      validity, stability, and reliability were tested. RESULTS: Forty-six subjects
      were included in the symptomatic group (presence of "urgency"), and seventeen
      were included in the asymptomatic group (control group). There was difference
      between symptomatic and asymptomatic subjects on all of the subscales (p<=0.001).
      The UQ subscales correlated with the OABq-SF subscales (p<=0.01), except the
      subscale "time to control urgency" and the item "impact" from the visual analog
      scales (VAS). However, these scales correlated with the OABq-SF - Symptom Bother
      Scale. The UQ subscales demonstrated stability over time (p<0.05), but the
      subscale "fear of incontinence" and the item "severity" of the VAS did not. All
      of the UQ subscales showed internal consistencies that were considered to be good
      or excellent. CONCLUSION: The Portuguese version of the UQ proved to be a valid
      tool for the evaluation of OAB in individuals whose native language is
      Portuguese.

PMID- 29219283
TI  - Comparative differences between T1a/b and T1e/m as substages in T1 urothelial
      carcinoma of the bladder.
AB  - OBJECTIVE: To evaluate the prognostic value of the depth of lamina propria
      invasion in patients with T1 bladder cancer and to display comparative
      differences between the T1a/b and T1e/m substaging systems. PATIENTS AND METHODS:
      This study included 106 patients with primary stage T1 urothelial bladder tumours
      who underwent surgery between January 2009 and December 2014. Pathologic
      specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the
      same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour
      size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging
      system were investigated to detect the relation between disease progression and
      recurrence. RESULTS: The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b
      (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively
      (p=0.446). There was no significant difference between the substaging groups for
      disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs.
      T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm
      (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent
      predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial
      method, recurrence-free survival was significantly different in patients with
      pT1a tumours compared with those with pT1b tumours (p=0.033). CONCLUSIONS:
      Substaging T1 provides a prediction of disease recurrence. Regarding recurrence,
      T1a/b substaging can provide better knowledge of disease behaviour because it is
      predicted as more superior than T1 m/e, and it can help in determining the
      requirement for early cystectomy.

PMID- 29219284
TI  - Does a previous prostate biopsy-related acute bacterial prostatitis affect the
      results of radical prostatectomy?
AB  - OBJECTIVE: To The standard technique for obtaining a histologic diagnosis of
      prostatic carcinomas is transrectal ultrasound guided prostate biopsy. Acute
      prostatitis which might develop after prostate biopsy can cause periprostatic
      inflammation and fibrosis. In this study, we performed a retrospective review of
      our database to determine whether ABP history might affect the outcome of RP.
      MATERIALS AND METHODS: 441 RP patients who were operated in our clinic from 2002
      to 2014 were included in our study group. All patients' demographic values, PSA
      levels, biopsy and radical prostatectomy specimen pathology results and their
      perioperative/postoperative complications were evaluated. RESULTS: There were 41
      patients in patients with acute prostatitis following biopsy and 397 patients
      that did not develop acute prostatitis. Mean blood loss, transfusion rate and
      operation period were found to be significantly higher in ABP patients.
      Hospitalization period and reoperation rates were similar in both groups.
      However, post-op complications were significantly higher in ABP group.
      CONCLUSION: Even though it does not affect oncological outcomes, we would like to
      warn the surgeons for potential complaints during surgery in ABP patients.

PMID- 29219285
TI  - Bull In the Middle: Always stay alert and be prepared to take action.

PMID- 29219286
TI  - Fire-Based EMS Community Health Care Guide: NFPA guide to offer roadmap to
      implementing a community paramedicine program.

PMID- 29219287
TI  - Data Scrutiny: Focus on training and compliance to reduce risk of fraud.

PMID- 29219288
TI  - Mysterious Weakness: Life-threatening condition can be managed in the field.

PMID- 29219289
TI  - Crawl, Walk, Run: Various modalities can enhance and improve activity
      effectiveness.

PMID- 29219290
TI  - Send in the Drone: Getting care to patients faster with unmanned aerial vehicles.

PMID- 29219291
TI  - Atomic Layer Deposition of Lithium Niobium Oxides as Potential Solid-State
      Electrolytes for Lithium-Ion Batteries.
AB  - The development of solid-state electrolytes by atomic layer deposition (ALD)
      holds unparalleled advantages toward the fabrication of next-generation solid
      state batteries. Lithium niobium oxide (LNO) thin films with well-controlled film
      thickness and composition were successfully deposited by ALD at a deposition
      temperature of 235  degrees C using lithium tert-butoxide and niobium ethoxide as
      Li and Nb sources, respectively. Furthermore, incorporation of higher Li content
      was achieved by increasing the Li-to-Nb subcycle ratio. In addition, detailed X
      ray absorption near edge structure studies of the amorphous LNO thin films on the
      Nb L-edge revealed the existence of Nb as Nb5+ in a distorted octahedral
      structure. The octahedrons in niobium oxide thin films experienced severe
      distortions, which could be gradually alleviated upon the introduction of Li
      atoms into the thin films. The ionic conductivities of the as-prepared LNO thin
      films were also measured, with the highest value achieving 6.39 * 10-8 S cm-1 at
      303 K with an activation energy of 0.62 eV.

PMID- 29219292
TI  - Self-Assembly of Porous Boron Nitride Microfibers into Ultralight Multifunctional
      Foams of Large Sizes.
AB  - As a kind of macroscopic boron nitride (BN) architectures, ultralight BN cellular
      materials with high porosity and great resilience would have a broad range of
      applications in energy and environment areas. However, creating such BN cellular
      materials in large sizes has still been proven challenging. Here, we report on
      the unique self-assembly of one-dimensional porous BN microfibers into an
      integral three-dimensional BN foam with open-cell cellular architectures. An
      ultrasonic-assisted self-assembly, freeze-drying, and high-temperature pyrolysis
      process has been developed for the preparation of cellular BN foam with a large
      size and desired shape. The developed BN foam has low density, high porosity
      (~99.3%), great resilience, and excellent hydrophobic-lipophilic nature. The foam
      also exhibits excellent absorption capacities for a wide range of organic
      solvents and oils (wt % of ~5130-7820%), as well as a high recovery efficiency
      (~94%). Moreover, the unique hierarchical porous structure enables the foam to
      demonstrate a very low thermal conductivity (~0.035 W/K/m). The excellent thermal
      insulation performance, superior mechanical property, and superb chemical and
      thermal stability enable the developed BN foam as an integrating multifunctional
      material in a broad range of high-end applications.

PMID- 29219293
TI  - Correction to Facile Coordination-Precipitation Route to Insoluble Metal
      Roussin's Black Salts for NIR-Responsive Release of NO for Anti-Metastasis.

PMID- 29219294
TI  - TiO2 Nanorod Arrays with Mesoscopic Micro-Nano Interfaces for in Situ Regulation
      of Cell Morphology and Nucleus Deformation.
AB  - Cell morphology and nucleus deformation are important when circulating tumor
      cells break away from the primary tumor and migrate to a distant organ. Cells are
      sensitive to the microenvironment and respond to the cell-material interfaces. We
      fabricated TiO2 nanorod arrays with mesoscopic micro-nano interfaces through a
      two-step hydrothermal reaction method to induce severe changes in cell morphology
      and nucleus deformation. The average size of the microscale voids was increased
      from 5.1 to 10.5 MUm when the hydrothermal etching time was increased from 3 to
      10 h, whereas the average distances between voids were decreased from 0.88 to
      0.40 MUm. The nucleus of the MCF-7 cells on the TiO2 nanorod substrate that was
      etched for 10 h exhibited a significant deformation, because of the large size of
      the voids and the small distance between voids. Nucleus defromation was
      reversible during the cells proliferate process when the cells were cultured on
      the mesoscopic micro-nano interface.This reversible process was regulated by
      combining of the uniform pressure applied by the actin cap and the localized
      pressure applied by the actin underneath the nucleus. Cell morphology and nucleus
      shape interacted with each other to adapt to the microenvironment. This
      mesoscopic micro-nano interface provided a new insight into the cell-biomaterial
      interface to investigate cell behaviors.

PMID- 29219295
TI  - Carbon with Expanded and Well-Developed Graphene Planes Derived Directly from
      Condensed Lignin as a High-Performance Anode for Sodium-Ion Batteries.
AB  - In this study, we demonstrate that lignin, which constitutes 30-40 wt % of the
      terrestrial lignocellulosic biomass and is produced from second generation
      biofuel plants as a cheap byproduct, is an excellent precursor material for
      sodium-ion battery (NIB) anodes. Because it is rich in aromatic monomers that are
      highly cross-linked by ether and condensed bonds, the lignin material carbonized
      at 1300  degrees C (C-1300) in this study has small graphitic domains with well
      developed graphene layers, a large interlayer spacing (0.403 nm), and a high
      micropore surface area (207.5 m2 g-1). When tested as an anode in an NIB, C-1300
      exhibited an initial Coulombic efficiency of 68% and a high reversible capacity
      of 297 mA h g-1 at 50 mA g-1 after 50 cycles. The high capacity of 199 mA h g-1
      at less than 0.1 V with a flat voltage profile and an extremely low charge
      discharge voltage hysteresis (<0.03 V) make C-1300 a promising energy-dense
      electrode material. In addition, C-1300 exhibited an excellent high-rate
      performance of 116 mA h g-1 at 2.5 A g-1 and showed stable cycling retention
      (0.2% capacity decay per cycle after 500 cycles). By comparing the properties of
      the lignin-derived carbon with oak sawdust-derived and sugar-derived carbons and
      a low-temperature carbonized sample (900  degrees C), the reasons for the
      excellent performance of C-1300 were determined to result from facilitated Na+
      ion transport to the graphitic layer and the microporous regions that penetrate
      through the less defective and enlarged interlayer spacings.

PMID- 29219296
TI  - Remediation of Polluted Soil in China: Policy and Technology Bottlenecks.

PMID- 29219297
TI  - Expanding the Chemistry of Rhenium Metal-Metal Bonded Fluoro Complexes: Facile
      Preparation and Characterization of Paddlewheel Complexes.
AB  - Quadruply bonded rhenium(III) dimers with the stoichiometry Re2L4F2 (1, L =
      hexahydro-2H-pyrimido[1,2a]pyrimidinate (hpp-); 2, L = diphenyl formamidinate
      (dpf-)) were prepared from the solid-state melt reactions (SSMRs) between
      (NH4)2[Re2F8].2H2O and HL. Those compounds were characterized in the solid state
      by single-crystal X-ray diffraction and in solution by UV-visible spectroscopy
      and cyclic voltammetry. The compound [Re2(hpp)4F2]PF6 (3) was prepared from the
      one-electron oxidation of Re2(hpp)4F2 with [Cp2Fe]PF6. Compounds 1-3 are
      isostructural with the corresponding chloro derivatives. In solution, compound 1
      undergoes two one-electron oxidations. Comparison with its higher halogen
      homologues reveals that Re2(hpp)4F2 (1) is more easily oxidized than its chloro
      and bromo analogues.

PMID- 29219298
TI  - Highly Selective Red-Emitting Fluorescent Probe for Imaging Cancer Cells in Situ
      by Targeting Pim-1 Kinase.
AB  - Based on the fact that enzyme-targeting probes are highly sensitive and
      selective, a novel red-emitting probe (NB-BF) for Pim-1 kinase including three
      parts, fluorophore (NB), linker, and inhibitor (BF), has been designed for cancer
      optical imaging. In its free state, NB-BF is folded and the fluorescence quenched
      by PET between fluorophore and inhibitor both in PBS buffer and in normal cells.
      Significantly, it emitted strong red fluorescence in Pim-1 overexpressed cancer
      cells. The specificity of NB-BF for Pim-1 kinase was directly demonstrated by
      gene silencing analysis. Furthermore, it is the first time to know where Pim-1
      kinase mainly distributes at mitochondria with Pearson's correlation factor (Rr)
      of 0.965 and to provide a fluorescent tool to verify the function of the Pim-1
      kinase. More importantly, NB-BF was applied in tissue imaging and preferentially
      labeled tumors in vivo.

PMID- 29219299
TI  - Highly Proton Conducting Polyelectrolyte Membranes with Unusual Water Swelling
      Behavior Based on Triptycene-containing Poly(arylene ether sulfone) Multiblock
      Copolymers.
AB  - Multiblock poly(arylene ether sulfone) copolymers are attractive for
      polyelectrolyte membrane fuel cell applications due to their reportedly improved
      proton conductivity under partially hydrated conditions and better
      mechanical/thermal stability compared to Nafion. However, the long hydrophilic
      sequences required to achieve high conductivity usually lead to excessive water
      uptake and swelling, which degrade membrane dimensional stability. Herein, we
      report a fundamentally new approach to address this grand challenge by
      introducing shape-persistent triptycene units into the hydrophobic sequences of
      multiblock copolymers, which induce strong supramolecular chain-threading and
      interlocking interactions that effectively suppress water swelling. Consequently,
      unlike previously reported multiblock copolymer systems, the water swelling of
      the triptycene-containing multiblock copolymers did not increase proportionally
      with water uptake. This combination of high water uptake and low swelling
      behavior of these copolymers resulted in excellent proton conductivity and
      membrane dimensional stability under fully hydrated conditions. In particular,
      the triptycene-containing multiblock copolymer film with the longest hydrophilic
      block length (i.e., BPSH100-TRP0-15k-15k) had a water uptake of 105%, an
      excellent proton conductivity of 0.150 S/cm, and a volume swelling ratio of just
      29% (more than 42% reduction compared to Nafion 212).

PMID- 29219300
TI  - Intermetallic: A Pseudoelement for Catalysis.
AB  - A clear correlation between electronic structure and CO2 selectivity for steam
      reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd
      intermetallics on the basis of experiments and calculations. In order to rule out
      the effects of oxide supports, the intermetallic powders were simply prepared by
      alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd
      exhibit valence electronic densities of states similar to that of Cu and
      significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to
      pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy
      (HXPS) measurements and density functional theory (DFT) calculations.
      Consequently, they show the similar high selectivity of CO2 for the SRM reaction.
      However, this is not the case for PtZn and NiZn because of the slight differences
      in their valence electronic structures from that of PdZn. The interval between
      the Fermi level and the top of the d band is closely related to the selectivity
      of CO2 for the SRM: the larger the interval is, the higher is the selectivity of
      CO2. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys.
      Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in
      an equimolar ratio are more stable than the (001) or (110) surfaces terminated by
      alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn,
      and NiZn show that bond breaking on the surface leads to a reduction in the d
      bandwidth but that the d band for stable (111) or (100) surfaces remains
      essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd
      do not contain Cu but show similar valence electronic structure and catalytic
      selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as
      pseudoelements of Cu. The basis of this concept is like electronic structure,
      like catalysis, which has been demonstrated by experiments and calculations. This
      is a logical way to enable us to look for new catalysts in which precious metals
      are partially or completely replaced by base metals. We do not expect that this
      concept can be applied to all catalytic reactions, but this approach is one of
      most promising ways to derive a better understanding of the origin of catalytic
      mechanisms and eventually allow us to design useful catalysts intentionally in
      the future. This Account reviews the authors' published works on this topic.

PMID- 29219301
TI  - High-Performance Sub-Micrometer Channel WSe2 Field-Effect Transistors Prepared
      Using a Flood-Dike Printing Method.
AB  - Printing technology has potential to offer a cost-effective and scalable way to
      fabricate electronic devices based on two-dimensional (2D) transition metal
      dichalcogenides (TMDCs). However, limited by the registration accuracy and
      resolution of printing, the previously reported printed TMDC field-effect
      transistors (FETs) have relatively long channel lengths (13-200 MUm), thus
      suffering low current-driving capabilities (<=0.02 MUA/MUm). Here, we report a
      "flood-dike" self-aligned printing technique that allows the formation of
      source/drain metal contacts on TMDC materials with sub-micrometer channel lengths
      in a reliable way. This self-aligned printing technique involves three steps: (i)
      printing of gold ink on a WSe2 flake to form the first gold electrode, (ii)
      modifying the surface of the first gold electrode with a self-assembled monolayer
      (SAM) to lower the surface tension and render the surface hydrophobic, and (iii)
      printing of gold ink close to the SAM-treated first electrode at a certain
      distance. During the third step, the gold ink would first spread toward the edge
      of the first electrode and then get stopped by the hydrophobic SAM coating,
      ending up forming a sub-micrometer channel. With this printing technique, we have
      successfully downscaled the channel length to ~750 nm and achieved enhanced on
      state current densities of ~0.64 MUA/MUm (average) and high on/off current ratios
      of ~3 * 105 (average). Furthermore, with our high-performance printed WSe2 FETs,
      driving capabilities for quantum-dot light-emitting diodes (LEDs), inorganic
      LEDs, and organic LEDs have been demonstrated, which reveals the potential of
      using printed TMDC electronics for display backplane applications.

PMID- 29219302
TI  - Oxidation of Titanocene(III): The Deceptive Simplicity of a Color Change.
AB  - Reduction of red Cp2TiCl2 (Cp = cyclopentadienyl) with zinc dust in acetonitrile
      produces a blue solution of [Cp2Ti(NCMe)2]+, which when exposed to air rapidly
      discolors to bright yellow. This behavior makes the blue solution a handy visual
      indicator for the presence of oxygen, but the chemistry is considerably more
      complicated than the primary colors suggest at first glance. Real-time mass
      spectrometric and colorimetric analysis reveals that oxidation from Ti(III) to
      Ti(IV) produces a host of oxygen-containing complexes, whose appearance parallels
      the observed color changes.

PMID- 29219303
TI  - Explosive Reaction for Barium Niobium Perovskite Oxynitride.
AB  - An intense exothermic and explosive reaction between Ba(OH)2, NbCl5, and NaNH2
      produced barium niobium perovskite oxynitride in seconds. The addition of hexane
      reduced the risk of explosion during mixing of the starting materials, and
      subsequent heat treatment at 498 K in hexane allowed control of this exothermic
      reaction, leading to formation of the perovskite oxynitride with fewer
      impurities. The synthesis of barium tantalum perovskite oxynitride under similar
      reaction conditions was successful.

PMID- 29219304
TI  - van der Waals Layered Materials: Opportunities and Challenges.
AB  - Since graphene became available by a scotch tape technique, a vast class of two
      dimensional (2D) van der Waals (vdW) layered materials has been researched
      intensively. What is more intriguing is that the well-known physics and chemistry
      of three-dimensional (3D) bulk materials are often irrelevant, revealing exotic
      phenomena in 2D vdW materials. By further constructing heterostructures of these
      materials in the planar and vertical directions, which can be easily achieved via
      simple exfoliation techniques, numerous quantum mechanical devices have been
      demonstrated for fundamental research and technological applications. It is,
      therefore, necessary to review the special features in 2D vdW materials and to
      discuss the remaining issues and challenges. Here, we review the vdW materials
      library, technology relevance, and specialties of vdW materials covering the vdW
      interaction, strong Coulomb interaction, layer dependence, dielectric screening
      engineering, work function modulation, phase engineering, heterostructures,
      stability, growth issues, and the remaining challenges.

PMID- 29219305
TI  - Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans.
AB  - Brucellosis is a serious zoonotic bacterial disease that is ranked by the World
      Health Organization among the top seven "neglected zoonoses" that threaten human
      health and cause poverty. It is a costly, highly contagious disease that affects
      ruminants, cattle, sheep, goats, and other productive animals such as pigs.
      Symptoms include abortions, infertility, decreased milk production, weight loss,
      and lameness. Brucellosis is also the most common bacterial disease that is
      transmitted from animals to humans, with approximately 500 000 new human cases
      each year. Detection and slaughter of infected animals is required to eradicate
      the disease, as vaccination alone is currently insufficient. However, as the most
      protective vaccines compromise serodiagnosis, this creates policy dilemmas, and
      these often result in the failure of eradication and control programs. Detection
      of antibodies to the Brucella bacterial cell wall O-polysaccharide (OPS)
      component of smooth lipopolysaccharide is used in diagnosis of this disease, and
      the same molecule contributes important protective efficacy to currently deployed
      veterinary whole-cell vaccines. This has set up a long-standing paradox that
      while Brucella OPS confers protective efficacy to vaccines, its presence results
      in similar antibody profiles in infected and vaccinated animals. Consequently,
      differentiation of infected from vaccinated animals (DIVA) is not possible, and
      this limits efforts to combat the disease. Recent clarification of the chemical
      structure of Brucella OPS as a block copolymer of two oligosaccharide sequences
      has provided an opportunity to utilize unique oligosaccharides only available via
      chemical synthesis in serodiagnostic tests for the disease. These
      oligosaccharides show excellent sensitivity and specificity compared with the
      native polymer used in current commercial tests and have the added advantage of
      assisting discrimination between brucellosis and infections caused by several
      bacteria with OPS that share some structural features with those of Brucella.
      During synthesis and immunochemical evaluation of these synthetic antigens, it
      became apparent that an opportunity existed to create a polysaccharide-protein
      conjugate vaccine that would not create antibodies that give false positive
      results in diagnostic tests for infection. This objective was reduced to
      practice, and immunization of mice showed that antibodies to the Brucella A
      antigen could be developed without reacting in a diagnostic test based on the M
      antigen. A conjugate vaccine of this type could readily be developed for use in
      humans and animals. However, as chemical methods advance and modern methods of
      bacterial engineering mature, it is expected that the principles elucidated by
      these studies could be applied to the development of an inexpensive and cost
      effective vaccine to combat endemic brucellosis in animals.

PMID- 29219307
TI  - FeCl3-Promoted [3 + 2] Annulations of gamma-Butyrolactone Fused Cyclopropanes
      with Heterocumulenes.
AB  - The [3 + 2] annulations of gamma-butyrolactone fused donor-acceptor (D-A)
      cyclopropanes with aromatic isothiocyanates and dialkyl carbodiimides promoted by
      FeCl3 is reported. A series of bicyclic/polycyclic gamma-butyrolactone fused
      thioimidates and gamma-butyrolactone fused amidines containing four contiguous
      stereogenic centers were obtained in excellent yields as single stereoisomers.

PMID- 29219306
TI  - The Key RuV=O Intermediate of Site-Isolated Mononuclear Water Oxidation Catalyst
      Detected by in Situ X-ray Absorption Spectroscopy.
AB  - Improvement of the oxygen evolution reaction (OER) is a challenging step toward
      the development of sustainable energy technologies. Enhancing the OER rate and
      efficiency relies on understanding the water oxidation mechanism, which entails
      the characterization of the reaction intermediates. Very active Ru-bda type (bda
      is 2,2'-bipyridine-6,6'-dicarboxylate) molecular OER catalysts are proposed to
      operate via a transient 7-coordinate RuV?O intermediate, which so far has never
      been detected due to its high reactivity. Here we prepare and characterize a well
      defined supported Ru(bda) catalyst on porous indium tin oxide (ITO) electrode.
      Site isolation of the catalyst molecules on the electrode surface allows trapping
      of the key 7-coordinate RuV?O intermediate at potentials above 1.34 V vs NHE at
      pH 1, which is characterized by electron paramagnetic resonance and in situ X-ray
      absorption spectroscopies. The in situ extended X-ray absorption fine structure
      analysis shows a Ru?O bond distance of 1.75 +/- 0.02 A, consistent with
      computational results. Electrochemical studies and density functional theory
      calculations suggest that the water nucleophilic attack on the surface-bound
      RuV?O intermediate (O-O bond formation) is the rate limiting step for OER
      catalysis at low pH.

PMID- 29219308
TI  - BF3.OEt2-Mediated Tandem Annulation: A Strategy To Construct Functionalized
      Chromeno- and Pyrano-Fused Pyridines.
AB  - A simple and efficient one-pot annulation of arylidenones, alkynes, and nitriles
      in the presence of BF3.OEt2 is described. A highly functionalized variety of N
      substituted pyridine-fused chromeno and pyrano derivatives were obtained with
      satisfactory yields under mild reaction conditions. The method was proven to be
      valid for the synthesis of a diverse library of chromeno[3,4-c]pyridines,
      thiochromeno[3,4-c]pyridines, pyrano[3,4-c]pyridines, and thiopyrano[3,4
      c]pyridine derivatives from readily accessible substrates. This experimentally
      simple protocol provides structurally complex, biologically relevant heterocycles
      in a one-pot operation.

PMID- 29219309
TI  - Assessing the Potential for Oligomer Formation from the Reactions of Lactones in
      Secondary Organic Aerosols.
AB  - Laboratory and field measurements have demonstrated that 2-methyl glyceric acid
      (2-MG) is the base component of a wide range of chemical species found in
      methacrolein-derived secondary organic aerosol (SOA). In order to explore the
      recently proposed hypothesis that a lactone oxidation intermediate is the origin
      of 2-MG and its derivatives in SOA, nuclear magnetic resonance techniques were
      used to study kinetics and reaction products of the aqueous phase reactions of a
      model lactone, beta-propiolactone (BPL). BPL was found to react with a lifetime
      of 4-10 h (depending on solution conditions) via a general acid catalyzed
      mechanism, which suggests that lactones similar to BPL are reactive on an
      atmospherically relevant time scale. BPL was also shown to form a variety of
      nucleophilic addition products (organosulfates and nitrates and oligomers)
      similar to the 2-MG-based species observed in previous experiments involving the
      photooxidation and SOA processing of methacrolein. While many of the BPL reaction
      products could be rationalized via an epoxide-like nucleophilic addition
      mechanism, evidence for ester-like nucleophilic addition was suggested through
      the observation of inorganic ion-catalyzed oligomer formation. The formation of
      oligomers was found to depend strongly on the proportion of organic acid
      nucleophile present in its deprotonated form. Therefore, due to the nature of the
      general acid catalysis and importance of deprotonated acids for efficient BPL
      oligomerization, it is suggested that oligomerization from lactone intermediates
      will be more efficient at higher SOA pH values. This result may help explain why
      overall isoprene-derived SOA formation has been observed to be largely pH
      independent. Overall, the results strongly support the previous conclusion that a
      lactone intermediate is responsible for the formation of 2-MG-related species
      found in methacrolein-derived SOA.

PMID- 29219310
TI  - Synchrotron Photoionization Study of Furan and 2-Methylfuran Reactions with
      Methylidyne Radical (CH) at 298 K.
AB  - The reactions of furan and 2-methylfuran with methylidyne CH (X2Pi) radical were
      investigated at 298 K using synchrotron radiation produced at the Advanced Light
      Source of the Lawrence Berkeley National Laboratory. Reaction products were
      observed by multiplexed photoionization mass spectrometry and characterized based
      on their photoionization spectra and kinetic time traces. Primary products
      observed in furan + CH are 2,4-cyclopentadien-1-one (m/z = 80), 2-penten-4-ynal
      (m/z = 80), and vinylacetylene (m/z = 52). From 2-methylfuran + CH, 2-4
      cyclopentadien-1-carbaldehyde (m/z = 94), 2,3,4-hexatrienal (m/z = 94), 1,3
      cyclopentadiene (m/z = 66), 3-penten-1-yne (Z) (m/z = 66), and vinylacetylene
      (m/z = 52) are the primary products observed. Using potential energy surface
      scans, thermodynamically favorable reaction pathways are proposed. CH addition to
      the pi-bonds in furan and 2-methylfuran rings was found to be the entrance
      channel that led to formation of all identified primary products. Both reactions
      follow patterns of H loss and CHO loss, as well as formation of cyclic and
      acyclic isomers.

PMID- 29219311
TI  - Multicomponent, Enantioselective Michael-Michael-Aldol-beta-Lactonizations
      Delivering Complex beta-Lactones.
AB  - Optically active, tertiary amine Lewis bases react with unsaturated acid
      chlorides to deliver chiral, alpha,beta-unsaturated acylammonium salts. These
      intermediates participate in a catalytic, enantioselective, three-component
      process delivering bi- and tricyclic beta-lactones through a Michael-Michael
      aldol-beta-lactonization. In a single operation, the described multicomponent,
      organocascade process forms complex bi- and tricyclic beta-lactones by generating
      four new bonds, two rings, and up to four contiguous stereocenters. In the
      racemic series, yields of 22-75% were achieved using 4-pyrrolidinopyridine as
      Lewis base. In the enantioselective series employing isothiourea catalysts, a
      kinetic resolution of the initially formed racemic Michael adduct appears
      operative, providing yields of 46% to quantitative (based on 50% max) with up to
      94:6 er. Some evidence for a dynamic kinetic asymmetric transformation for
      tricyclic-beta-lactone 1d was obtained following optimization (yields up to 61%,
      94:6 er) through a presumed reversible Michael.

PMID- 29219312
TI  - Broad Synthesis of Disubstituted Dihydrofuran-Fused [60]Fullerene Derivatives via
      Cu(I)/Ag(I)-Mediated Synergistic Annulation Reaction.
AB  - A novel and efficient Cu(I)/Ag(I)-mediated synergistic annulation reaction of
      [60]fullerene with diarylethanones, benzoylacetonitriles, and beta-dicarbonyl
      compounds has been developed for the direct construction of diverse disubstituted
      dihydrofuran-fused [60]fullerene derivatives. This transformation exhibits a
      remarkably broad substrate scope and functional group tolerance and provides a
      useful method to a scarce class of fullerene derivatives.

PMID- 29219313
TI  - Characterizing the Tautomers of Protonated Aniline Using Differential Mobility
      Spectrometry and Mass Spectrometry.
AB  - The site of protonation for gas-phase aniline has been debated for many years,
      with many research groups contributing experimental and computational evidence
      for either the amino-protonated or the para-carbon-protonated tautomer as the gas
      phase global minimum structure. Here, we employ differential mobility
      spectrometry (DMS) and mass spectrometry (MS) to separate and characterize the
      amino-protonated (N-protonated) and para-carbon-protonated ( p-protonated)
      tautomers of aniline. We demonstrate that upon electrospray ionization (ESI),
      aniline is protonated predominantly at the amino position. Similar analyses are
      conducted on another three isotopically labeled forms of aniline to confirm our
      structural assignments. We observe a significant reduction of the relative
      population of the p-protonated tautomer when a protic ESI solvent is employed
      (methanol/water) compared to when an aprotic solvent (acetonitrile) is employed.
      We also observe conversion of the p-protonated species into the N-protonated
      species upon clustering with protic solvent vapor post-DMS selection-a finding
      supported by previous experimental data acquired using DMS-MS.

PMID- 29219314
TI  - Isoprene-Derived Organosulfates: Vibrational Mode Analysis by Raman Spectroscopy,
      Acidity-Dependent Spectral Modes, and Observation in Individual Atmospheric
      Particles.
AB  - Isoprene, the most abundant biogenic volatile organic compound (BVOC) in the
      atmosphere, and its low-volatility oxidation products lead to secondary organic
      aerosol (SOA) formation. Isoprene-derived organosulfates formed from reactions of
      isoprene oxidation products with sulfate in the particle phase are a significant
      component of SOA and can hydrolyze forming polyols. Despite characterization by
      mass spectrometry, their basic structural and spectroscopic properties remain
      poorly understood. Herein, Raman microspectroscopy and density functional theory
      (DFT) calculations (CAM-B3LYP level of theory) were combined to analyze the
      vibrational modes of key organosulfates, 3-methyltetrol sulfate esters (racemic
      mixture of two isomers), and racemic 2-methylglyceric acid sulfate ester, and
      hydrolysis products, 2-methyltetrols, and 2-methylglyceric acid. Two intense
      vibrational modes were identified, nu(RO-SO3) (846 +/- 4 cm-1) and nus(SO3) (1065
      +/- 2 cm-1), along with a lower intensity delta(SO3) mode (586 +/- 2 cm-1). For 2
      methylglyceric acid and its sulfate esters, deprotonation of the carboxylic acid
      at pH values above the pKa decreased the carbonyl stretch frequency (1724 cm-1),
      while carboxylate modes grew in for nus(COO-) and nua(COO-) at 1413 and 1594 cm
      1, respectively. The nu(RO-SO3) and nus(SO3) modes were observed in individual
      atmospheric particles and can be used in future studies of complex SOA mixtures
      to distinguish organosulfates from inorganic sulfate or hydrolysis products.

PMID- 29219315
TI  - Calculation of Standard Reduction Potentials of Amino Acid Radicals and the
      Effects of Water and Incorporation into Peptides.
AB  - Guanine (Guo) is generally accepted as the most easily oxidized DNA base when
      cells are subjected to ionizing radiation; calculations of the standard reduction
      potential of the guanyl radical, Eo(Guo*+/Guo) are within ~0.1 V of experimental
      values in aqueous solution extrapolated to standard conditions. While a number of
      experimental studies have shown some amino acid radicals have redox properties at
      pH 7 which suggest or confirm a capacity for radical "repair" by electron
      transfer from the amino acid to Guo*+ (or its deprotonated conjugate), the redox
      properties of the radicals of other amino acids, including methionine, lysine and
      cystine, are less well characterized. In addition, the effects of incorporation
      of the amino acids into peptides, or the effects of water of hydration on
      calculated potentials, have not been extensively studied. In this work,
      calculations of standard reduction potentials of radicals from model amino acids
      as they appear in histone proteins are performed. To predict redox properties at
      pH 7, acid dissociation constants (pKas) of both radical and ground state amino
      acids are required. In some instances these are not experimentally determined and
      calculated pKas have been derived for some common amino acids and compared with
      experimental values.

PMID- 29219316
TI  - From the Promiscuous Asenapine to Potent Fluorescent Ligands Acting at a Series
      of Aminergic G-Protein-Coupled Receptors.
AB  - Monoamine neurotransmitters such as serotonin, dopamine, histamine, and
      noradrenaline have important and varied physiological functions and similar
      chemical structures. Representing important pharmaceutical drug targets, the
      corresponding G-protein-coupled receptors (termed aminergic GPCRs) belong to the
      class of cell membrane receptors and share many levels of similarity as well.
      Given their pharmacological and structural closeness, one could hypothesize the
      possibility to derivatize a ubiquitous ligand to afford rapidly fluorescent
      probes for a large set of GPCRs to be used for instance in FRET-based binding
      assays. Here we report fluorescent derivatives of the nonselective agent
      asenapine which were designed, synthesized, and evaluated as ligands of 34
      serotonin, dopamine, histamine, melatonin, acetylcholine, and adrenergic
      receptors. It appears that this strategy led rapidly to the discovery and
      development of nanomolar affinity fluorescent probes for 14 aminergic GPCRs.
      Selected probes were tested in competition binding assays with unlabeled
      competitors in order to demonstrate their suitability for drug discovery
      purposes.

PMID- 29219317
TI  - Single-Step Binary Electrostatic Directed Assembly of Active Nanogels for Smart
      Concentration-Dependent Encryption.
AB  - Anionic and cationic (N-isopropylacrylamide derivatives) active colloidal
      hydrogel nanoparticles, i.e., nanogels, are electrostatically assembled on
      surfaces to form microscale patterns with complex geometries. While using mixed
      dispersions of these two kinds of nanogels, we demonstrate the capability of
      sorting the nanogels in one step to form binary nanogel patterns on a surface.
      These patterns appear independently or simultaneously depending on the relative
      proportion of each nanogel type in the mixture. Hence, the resulting nanogel
      patterns provide quantitative information regarding the dispersion composition
      and can be used to achieve smart concentration-dependent nanogel encryption.
      Moreover, atomic force microscopy characterization measurements performed in
      liquid prove that the assembled nanogels maintain their swelling/deswelling
      properties once attached to the surface. Consequently, this method paves the way
      for applying such active nanogel patterns to produce smart coatings and sensors.

PMID- 29219318
TI  - How Inter- and Intramolecular Processes Dictate Aggregation-Induced Emission in
      Crystals Undergoing Excited-State Proton Transfer.
AB  - Aggregation-induced emission (AIE) offers a route for the development of
      luminescent technologies with high quantum efficiencies. Excited-state
      intramolecular proton transfer (ESIPT) coupled to AIE can produce devices with
      emission across the visible spectrum. We use a combination of theoretical models
      to determine the factors that mediate fluorescence in molecular crystals
      undergoing ESIPT. Using two materials based on 2'-hydroxychalcone as exemplar
      cases, we analyze how inter- and intramolecular processes determine the emissive
      properties in the crystal environment. This systematic investigation extends the
      current interpretation of AIE to polar chromophores with multiple decay pathways.
      We find that population of nonradiative pathways is dictated by the electronic
      effects of the substituents and the degree of distortion allowed in the crystal
      environment. Localization of the electron density is crucial to maximize
      fluorescence via ESIPT. Our conclusions offer design strategies for the
      development of luminescent molecular crystals.

PMID- 29219319
TI  - Cooperative Activating Effect of Tertiary Amine/DMSO on Elemental Sulfur: Direct
      Access to Thioaurones from 2'-Nitrochalcones under Mild Conditions.
AB  - A new mode for the activation of elemental sulfur is reported. In the presence of
      both DMSO and a tertiary aliphatic amine (triethylamine or N-methylpiperidine),
      this element reacts directly with a wide range of 2'-nitrochalcones 1 to provide
      the corresponding thioaurones 2 in high yields even at room temperature and in
      the absence of transition metal catalyst.

PMID- 29219320
TI  - Copper-Mediated Cascade C-H/N-H Annulation of Indolocarboxamides with Arynes:
      Construction of Tetracyclic Indoloquinoline Alkaloids.
AB  - An efficient and environmentally benign Cu-mediated method was developed for
      direct cascade C-H/N-H annulation to construct polyheterocyclic indoloquinoline
      scaffolds. This method highlights an emerging strategy for transforming inert C-H
      bonds into versatile functional groups in organic synthesis and provides a new
      versatile approach for the efficient synthesis of indolo[3,2-c] and [2,3
      c]quinoline alkaloids.

PMID- 29219321
TI  - SHetA2 Dry Powder Aerosols for Tuberculosis: Formulation, Design, and
      Optimization Using Quality by Design.
AB  - Tuberculosis (TB) is a life threatening pulmonary infection caused by
      Mycobacterium tuberculosis (MTB). Current treatments are complex, lengthy, and
      associated with severe side effects that decrease patient compliance and increase
      the probability of the emergence of drug resistant strains. Thus, more effective
      drugs with little to no side effects are needed to diversify the armamentarium
      against the global TB epidemic. SHetA2, an anticancer compound with null toxicity
      at doses much higher than the effective dose, was recently discovered to be
      active against MTB. In the present study, a dry powder formulation of SHetA2 for
      pulmonary delivery was developed to overcome its poor aqueous solubility and to
      maximize its concentration in the lungs, the main site of TB infection. Using
      quality by design (QbD) methodology, three different formulations of SHetA2
      microparticles (MPs) were designed, manufactured, and optimized, SHetA2 alone,
      SHetA2 PLGA, and SHetA2 mannitol MPs, to maximize the drug dose, target alveolar
      macrophages, and increase drug solubility, respectively. The resulting three
      SHetA2 MP formulations had spherical shape with particle size ranging from 1 to 3
      MUm and a narrow size distribution, suitable for uniform delivery to the alveolar
      region of the lungs. Upon dispersion with the Aerolizer dry powder inhaler (DPI),
      all three SHetA2 MP formulations had aerodynamic diameters smaller than 3.3 MUm
      and fine particle fractions (FPF4.46) greater than 77%. SHetA2 remained
      chemically stable after MP manufacture by spray drying, but the drug transformed
      from the crystalline to the amorphous form, which significantly enhanced the
      solubility of SHetA2. Using a custom-made dissolution apparatus, the FPF4.46 of
      SHetA2 MP dissolved much faster and to a greater extent (21.19 +/- 4.40%) than
      the unprocessed drug (3.51 +/- 0.9%). Thus, the physicochemical characteristics,
      in vitro aerosol performance, and dissolution rate of the optimized SHetA2 MPs
      appear to be suitable to achieve therapeutic concentrations in the lungs.

PMID- 29219322
TI  - Iridium-Catalyzed Hydrosilylation of Sulfur-Containing Olefins.
AB  - Hydrosilylation of various sulfur-containing olefins with (RO)3SiH has been
      achieved using iridium catalysts [IrX(cod)]2 (X = Cl, SPh). The catalysis is
      applicable to the chemoselective hydrosilylation of thioacetate, which enables
      the preparation of an industrially important silane coupling agent.

PMID- 29219323
TI  - Di-2-(2-oxindolin-3-ylidene)malononitrile Derivatives for N-Type Air-Stable
      Organic Field-Effect Transistors.
AB  - The nitrogenization of phenyl rings on DIM derivatives not only enhances
      molecular coplanarity but also stabilizes molecular LUMO levels, favoring charge
      transfer and improving air stability. Therefore, n-type organic field-effect
      transistors (OFETs) that are based on DIM-N2C8 with nitrogen atoms on both sides
      of the phenyl rings exhibit a moderate electron mobility of 0.059 cm2 V-1 s-1
      under ambient conditions.

PMID- 29219324
TI  - Total Synthesis of Huperzine R.
AB  - A total synthesis of huperzine R was accomplished. Intramolecular cycloaddition
      of a nitrile oxide and reductive cleavage of the resulting isoxazoline induced
      sequential cleavage of the C-C and C-O bonds to form the characteristic bicyclic
      lactam core with an enone moiety. Construction of the butenolide moiety from the
      enone afforded huperzine R.

PMID- 29219325
TI  - Role of Drug Adsorption onto the Silica Surface in Drug Release from Mesoporous
      Silica Systems.
AB  - Factors contributing to incomplete drug release from a number of mesoporous
      silica formulations are not well understood. This study aims to address this gap
      in knowledge by exploring the role of drug adsorption onto silica substrates
      during the drug release process in dissolution media. Adsorption isotherms were
      generated to understand drug adsorption behavior onto the silica surface. Two
      silica materials were selected (SBA-15 (mesoporous) and Aerosil 200 (nonporous))
      to investigate the influence of porous architecture on the adsorption/dissolution
      processes. The ability of the dissolution medium to wet the silica surface,
      particularly the porous network, was investigated by the addition of a surfactant
      to the dissolution medium. The results demonstrated that a larger amount of drug
      was bound/m2 to the nonporous surface than to the mesoporous material. Adsorption
      isotherms proved useful in understanding drug adsorption/release behavior for the
      nonporous silica formulation. However, the quantity of drug remaining on the
      mesoporous silica surface after dissolution was significantly higher than the
      amount predicted using adsorption isotherm data. These results suggest that a
      fraction of loaded drug molecules were tightly bound to the silica surface or
      attached to sites which are inaccessible for the dissolution media. The presence
      of surfactant, sodium dodecyl sulfate, in the media enhanced drug release from
      the silica surface. This behavior can be attributed to both the improved wetting
      characteristics of the media and adsorption of the surfactant to the silica
      surface. The findings of this study reinforce the significance of the role that
      silica porous architecture plays in the dissolution process and indicates that
      accessible surface area is an important parameter to consider for mesoporous
      systems in relation to drug release.

PMID- 29219326
TI  - Boosting the Efficiency of Quantum Dot-Sensitized Solar Cells through Formation
      of the Cation-Exchanged Hole Transporting Layer.
AB  - In search of a viable way to enhance the power conversion efficiency (PCE) of
      quantum dot-sensitized solar cells, we have designed a method by introducing a
      hole transporting layer (HTL) of p-type CuS through partial cation exchange
      process in a postsynthetic ligand-assisted assembly of nanocrystals (NCs). High
      quality CdSe and CdSSe gradient alloy NCs were synthesized through colloidal
      method, and the charge carrier dynamics was monitored through ultrafast transient
      absorption measurements. A notable increase in the short-circuit current
      concomitant with the increase in open-circuit voltage and the fill factor led to
      45% increment in PCE for CdSe-based solar cells upon formation of the CuS HTL.
      Electrochemical impedance spectroscopy further revealed that the CuS layer
      formation increases recombination resistance at the TiO2/NC/electrolyte
      interface, implying that interfacial recombination gets drastically reduced
      because of smooth hole transfer to the redox electrolyte. Utilizing the same
      approach for CdSSe alloy NCs, the highest PCE (4.03%) was obtained upon CuS layer
      formation compared to 3.26% PCE for the untreated one and 3.61% PCE with the
      conventional ZnS coating. Therefore, such strategies will help to overcome the
      kinetic barriers of hole transfer to electrolytes, which is one of the major
      obstacles of high-performance devices.

PMID- 29219327
TI  - Forced Imbibition in Porous Media: A Fourfold Scenario.
AB  - We establish a comprehensive description of the patterns formed when a wetting
      liquid displaces a viscous fluid confined in a porous medium. Building on model
      microfluidic experiments, we evidence four imbibition scenarios all yielding
      different large-scale morphologies. Combining high-resolution imaging and
      confocal microscopy, we show that they originate from two liquid-entrainment
      transitions and a Rayleigh-Plateau instability at the pore scale. Finally, we
      demonstrate and explain the long-time coarsening of the resulting patterns.

PMID- 29219328
TI  - Determination of Hydrogen Density by Swift Heavy Ions.
AB  - A novel method to determine the total hydrogen density and, accordingly, a
      precise plasma temperature in a lowly ionized hydrogen plasma is described. The
      key to the method is to analyze the energy loss of swift heavy ions interacting
      with the respective bound and free electrons of the plasma. A slowly developing
      and lowly ionized hydrogen theta-pinch plasma is prepared. A Boltzmann plot of
      the hydrogen Balmer series and the Stark broadening of the H_{beta} line
      preliminarily defines the plasma with a free electron density of (1.9+/
      0.1)*10^{16}  cm^{-3} and a free electron temperature of 0.8-1.3 eV. The
      temperature uncertainty results in a wide hydrogen density, ranging from
      2.3*10^{16} to 7.8*10^{18}  cm^{-3}. A 108 MHz pulsed beam of ^{48}Ca^{10+} with
      a velocity of 3.652  MeV/u is used as a probe to measure the total energy loss of
      the beam ions. Subtracting the calculated energy loss due to free electrons, the
      energy loss due to bound electrons is obtained, which linearly depends on the
      bound electron density. The total hydrogen density is thus determined as (1.9+/
      0.7)*10^{17}  cm^{-3}, and the free electron temperature can be precisely derived
      as 1.01+/-0.04  eV. This method should prove useful in many studies, e.g.,
      inertial confinement fusion or warm dense matter.

PMID- 29219330
TI  - Favorable Concurrence of Static and Dynamic Phenomena at the Morphotropic Phase
      Boundary of xBiNi_{0.5}Zr_{0.5}O_{3}-(1-x)PbTiO_{3}.
AB  - We reveal that concurrent events of inherent entropy boosting and increased
      synchronization between A- and B-site cation vibrations of an ABO_{3}-type
      perovskite structure give rise to a larger piezoelectric response in a
      ferroelectric system at its morphotropic phase boundary (MPB). It is further
      evident that the superior piezoelectric properties of xBiNi_{0.5}Zr_{0.5}O_{3}-(1
      x)PbTiO_{3} in comparison to xBiNi_{0.5}Ti_{0.5}O_{3}-(1-x)PbTiO_{3} are due to
      the absolute flattening of the local potentials for all ferroelectrically active
      cations with a higher spontaneous polarization at the MPB. These distinctive
      features are discovered from the analyses of neutron pair distribution functions
      and Raman scattering data at ambient conditions, which are particularly sensitive
      to mesoscopic-scale structural correlations. Altogether this uncovers more
      fundamental structure-property connections for ferroelectric systems exhibiting a
      MPB, and thereby has a critical impact in contriving efficient novel materials.

PMID- 29219331
TI  - Competition between Chaotic and Nonchaotic Phases in a Quadratically Coupled
      Sachdev-Ye-Kitaev Model.
AB  - The Sachdev-Ye-Kitaev (SYK) model is a concrete solvable model to study non-Fermi
      liquid properties, holographic duality, and maximally chaotic behavior. In this
      work, we consider a generalization of the SYK model that contains two SYK models
      with a different number of Majorana modes coupled by quadratic terms. This model
      is also solvable, and the solution shows a zero-temperature quantum phase
      transition between two non-Fermi liquid chaotic phases. This phase transition is
      driven by tuning the ratio of two mode numbers, and a nonchaotic Fermi liquid
      sits at the critical point with an equal number of modes. At a finite
      temperature, the Fermi liquid phase expands to a finite regime. More
      intriguingly, a different non-Fermi liquid phase emerges at a finite temperature.
      We characterize the phase diagram in terms of the spectral function, the Lyapunov
      exponent, and the entropy. Our results illustrate a concrete example of the
      quantum phase transition and critical behavior between two non-Fermi liquid
      phases.

PMID- 29219332
TI  - Heavy-Quark Symmetry Implies Stable Heavy Tetraquark Mesons Q_{i}Q_{j}q[over 
      ]_{k}q[over -]_{l}.
AB  - For very heavy quarks Q, relations derived from heavy-quark symmetry predict the
      existence of novel narrow doubly heavy tetraquark states of the form
      Q_{i}Q_{j}q[over -]_{k}q[over -]_{l} (subscripts label flavors), where q
      designates a light quark. By evaluating finite-mass corrections, we predict that
      double-beauty states composed of bbu[over -]d[over -], bbu[over -]s[over -], and
      bbd[over -]s[over -] will be stable against strong decays, whereas the double
      charm states ccq[over -]_{k}q[over -]_{l}, mixed beauty+charm states bcq[over 
      ]_{k}q[over -]_{l}, and heavier bbq[over -]_{k}q[over -]_{l} states will
      dissociate into pairs of heavy-light mesons. Observation of a new double-beauty
      state through its weak decays would establish the existence of tetraquarks and
      illuminate the role of heavy color-antitriplet diquarks as hadron constituents.

PMID- 29219333
TI  - Ultrafast Generation of Unconventional {001} Loops in Si.
AB  - Ultrafast laser annealing of ion implanted Si has led to thermodynamically
      unexpected large {001} self-interstitial loops, and the failure of Ostwald
      ripening models for describing self-interstitial cluster growth. We have carried
      out molecular dynamics simulations in combination with focused experiments in
      order to demonstrate that at temperatures close to the melting point, self
      interstitial rich Si is driven into dense liquidlike droplets that are highly
      mobile within the solid crystalline Si matrix. These liquid droplets grow by a
      coalescence mechanism and eventually transform into {001} loops through a liquid
      to-solid phase transition in the nanosecond time scale.

PMID- 29219334
TI  - Signatures of Electronic Structure in Bicircular High-Harmonic Spectroscopy.
AB  - High-harmonic spectroscopy driven by circularly polarized laser pulses and their
      counterrotating second harmonic is a new branch of attosecond science which
      currently lacks quantitative interpretations. We extend this technique to the
      midinfrared regime and record detailed high-harmonic spectra of several rare-gas
      atoms. These results are compared with the solution of the Schrodinger equation
      in three dimensions and calculations based on the strong-field approximation that
      incorporate accurate scattering-wave recombination matrix elements. A quantum
      orbit analysis of these results provides a transparent interpretation of the
      measured intensity ratios of symmetry-allowed neighboring harmonics in terms of
      (i) a set of propensity rules related to the angular momentum of the atomic
      orbitals, (ii) atom-specific matrix elements related to their electronic
      structure, and (iii) the interference of the emissions associated with electrons
      in orbitals corotating or counterrotating with the laser fields. These results
      provide the foundation for a quantitative understanding of bicircular high
      harmonic spectroscopy.

PMID- 29219335
TI  - Experimental Observation of Convective Cell Formation due to a Fast Wave Antenna
      in the Large Plasma Device.
AB  - An experiment in a linear device, the Large Plasma Device, is used to study
      sheaths caused by an actively powered radio frequency (rf) antenna. The rf
      antenna used in the experiment consists of a single current strap recessed inside
      a copper box enclosure without a Faraday screen. A large increase in the plasma
      potential was observed along magnetic field lines that connect to the antenna
      limiter. The electric field from the spatial variation of the rectified plasma
      potential generated E[over ->]*B[over ->]_{0} flows, often referred to as
      convective cells. The presence of the flows generated by these potentials is
      confirmed by Mach probes. The observed convective cell flows are seen to cause
      the plasma in front of the antenna to flow away and cause a density modification
      near the antenna edge. These can cause hot spots and damage to the antenna and
      can result in a decrease in the ion cyclotron range of frequencies antenna
      coupling.

PMID- 29219329
TI  - First Exclusive Measurement of Deeply Virtual Compton Scattering off ^{4}He:
      Toward the 3D Tomography of Nuclei.
AB  - We report on the first measurement of the beam-spin asymmetry in the exclusive
      process of coherent deeply virtual Compton scattering off a nucleus. The
      experiment uses the 6 GeV electron beam from the Continuous Electron Beam
      Accelerator Facility (CEBAF) accelerator at Jefferson Lab incident on a
      pressurized ^{4}He gaseous target placed in front of the CEBAF Large Acceptance
      Spectrometer (CLAS). The scattered electron is detected by CLAS and the photon by
      a dedicated electromagnetic calorimeter at forward angles. To ensure the
      exclusivity of the process, a specially designed radial time projection chamber
      is used to detect the recoiling ^{4}He nuclei. We measure beam-spin asymmetries
      larger than those observed on the free proton in the same kinematic domain. From
      these, we are able to extract, in a model-independent way, the real and imaginary
      parts of the only ^{4}He Compton form factor, H_{A}. This first measurement of
      coherent deeply virtual Compton scattering on the ^{4}He nucleus, with a fully
      exclusive final state via nuclear recoil tagging, leads the way toward 3D imaging
      of the partonic structure of nuclei.

PMID- 29219336
TI  - Giant Spin Lifetime Anisotropy in Graphene Induced by Proximity Effects.
AB  - We report on fundamental aspects of spin dynamics in heterostructures of graphene
      and transition metal dichalcogenides (TMDCs). By using realistic models derived
      from first principles we compute the spin lifetime anisotropy, defined as the
      ratio of lifetimes for spins pointing out of the graphene plane to those pointing
      in the plane. We find that the anisotropy can reach values of tens to hundreds,
      which is unprecedented for typical 2D systems with spin-orbit coupling and
      indicates a qualitatively new regime of spin relaxation. This behavior is
      mediated by spin-valley locking, which is strongly imprinted onto graphene by
      TMDCs. Our results indicate that this giant spin lifetime anisotropy can serve as
      an experimental signature of materials with strong spin-valley locking, including
      graphene-TMDC heterostructures and TMDCs themselves. Additionally, materials with
      giant spin lifetime anisotropy can provide an exciting platform for manipulating
      the valley and spin degrees of freedom, and for designing novel spintronic
      devices.

PMID- 29219337
TI  - Sliding Drops: Ensemble Statistics from Single Drop Bifurcations.
AB  - Ensembles of interacting drops that slide down an inclined plate show a
      dramatically different coarsening behavior as compared to drops on a horizontal
      plate: As drops of different size slide at different velocities, frequent
      collisions result in fast coalescence. However, above a certain size individual
      sliding drops are unstable and break up into smaller drops. Therefore, the long
      time dynamics of a large drop ensemble is governed by a balance of merging and
      splitting. We employ a long-wave film height evolution equation and determine the
      dynamics of the drop size distribution towards a stationary state from direct
      numerical simulations on large domains. The main features of the distribution are
      then related to the bifurcation diagram of individual drops obtained by numerical
      path continuation. The gained knowledge allows us to develop a Smoluchowski-type
      statistical model for the ensemble dynamics that well compares to full direct
      simulations.

PMID- 29219339
TI  - Unexpected Sensitivity of Nitrogen Ions Superradiant Emission on Pump Laser
      Wavelength and Duration.
AB  - Nitrogen molecules in ambient air exposed to an intense near-infrared femtosecond
      laser pulse give rise to cavity-free superradiant emission at 391.4 and 427.8 nm.
      An unexpected pulse duration-dependent cyclic variation of the superradiance
      intensity is observed when the central wavelength of the femtosecond pump laser
      pulse is finely tuned between 780 and 820 nm, and no signal occurs at the
      resonant wavelength of 782.8 nm (2omega_{782.8  nm}=omega_{391.4  nm}). On the
      basis of a semiclassical recollision model, we show that an interference of
      dipolar moments of excited ions created by electron recollisions explains this
      behavior.

PMID- 29219338
TI  - Publisher's Note: JLab Measurements of the ^{3}He Form Factors at Large Momentum
      Transfers [Phys. Rev. Lett. 119, 162501 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.162501.

PMID- 29219340
TI  - Superconducting-Gravimeter Tests of Local Lorentz Invariance.
AB  - Superconducting-gravimeter measurements are used to test the local Lorentz
      invariance of the gravitational interaction and of matter-gravity couplings. The
      best laboratory sensitivities to date are achieved via a maximum-reach analysis
      for 13 Lorentz-violating operators, with some improvements exceeding an order of
      magnitude.

PMID- 29219341
TI  - Interaction Dependent Heating and Atom Loss in a Periodically Driven Optical
      Lattice.
AB  - Periodic driving of optical lattices has enabled the creation of novel band
      structures not realizable in static lattice systems, such as topological bands
      for neutral particles. However, especially driven systems of interacting bosonic
      particles often suffer from strong heating. We have systematically studied
      heating in an interacting Bose-Einstein condensate in a driven one-dimensional
      optical lattice. We find interaction dependent heating rates that depend on both
      the scattering length and the driving strength and identify the underlying
      resonant intra- and interband scattering processes. By comparing the experimental
      data and theory, we find that, for driving frequencies well above the trap depth,
      the heating rate is dramatically reduced by the fact that resonantly scattered
      atoms leave the trap before dissipating their energy into the system. This
      mechanism of Floquet evaporative cooling offers a powerful strategy to minimize
      heating in Floquet engineered quantum gases.

PMID- 29219342
TI  - Block Analysis for the Calculation of Dynamic and Static Length Scales in Glass
      Forming Liquids.
AB  - We present block analysis, an efficient method of performing finite-size scaling
      for obtaining the length scale of dynamic heterogeneity and the point-to-set
      length scale for generic glass-forming liquids. This method involves considering
      blocks of varying sizes embedded in a system of a fixed (large) size. The length
      scale associated with dynamic heterogeneity is obtained from a finite-size
      scaling analysis of the dependence of the four-point dynamic susceptibility on
      the block size. The block size dependence of the variance of the alpha relaxation
      time yields the static point-to-set length scale. The values of the obtained
      length scales agree quantitatively with those obtained from other conventional
      methods. This method provides an efficient experimental tool for studying the
      growth of length scales in systems such as colloidal glasses for which performing
      finite-size scaling by carrying out experiments for varying system sizes may not
      be feasible.

PMID- 29219343
TI  - Revision of Bubble Bursting: Universal Scaling Laws of Top Jet Drop Size and
      Speed.
AB  - The collapse of a bubble of radius R_{o} at the surface of a liquid generating a
      liquid jet and a subsequent first drop of radius R is universally scaled using
      the Ohnesorge number Oh=MU/(rhosigmaR_{o})^{1/2} and a critical value Oh^{*}
      below which no droplet is ejected; rho, sigma, and MU are the liquid density,
      surface tension, and viscosity, respectively. First, a flow field analysis at
      ejection yields the scaling of R with the jet velocity V as R/l_{MU}~(V/V_{MU})^{
      5/3}, where l_{MU}=MU^{2}/(rhosigma) and V_{MU}=sigma/MU. This resolves the
      scaling problem of curvature reversal, a prelude to jet formation. In addition,
      the energy necessary for the ejection of a jet with a volume and averaged
      velocity proportional to R_{o}R^{2} and V, respectively, comes from the energy
      excess from the total available surface energy, proportional to sigmaR_{o}^{2},
      minus the one dissipated by viscosity, proportional to
      MU(sigmaR_{o}^{3}/rho)^{1/2}. Using the scaling variable phi=(Oh^{*}-Oh)Oh^{-2},
      it yields V/V_{MU}=k_{v}phi^{-3/4} and R/l_{MU}=k_{d}phi^{5/4}, which collapse
      published data since 1954 and resolve the scaling of R and V with k_{v}=16,
      k_{d}=0.6, and Oh^{*}=0.043 when gravity effects are negligible.

PMID- 29219344
TI  - Origin of Negative Longitudinal Piezoelectric Effect.
AB  - Piezoelectrics with negative longitudinal piezoelectric coefficients will
      contract in the direction of an applied electric field. Such piezoelectrics are
      thought to be rare, but there is no fundamental physics preventing the
      realization of negative longitudinal piezoelectric effect in a single-phase
      material. Using first-principles calculations, we demonstrate that several
      hexagonal ABC ferroelectrics possess significant negative longitudinal
      piezoelectric effects. The data mining of a first-principles-based database of
      piezoelectrics reveals that this effect is a general phenomenon. The origin of
      this unusual piezoelectric response relies on the strong ionic bonds associated
      with small effective charges and rigid potential energy surfaces. Moreover,
      ferroelectrics with negative longitudinal piezoelectric coefficients show
      anomalous pressure-enhanced ferroelectricity. Our results offer design principles
      to aid the search for new piezoelectrics for novel electromechanical device
      applications.

PMID- 29219345
TI  - Double-Cascade Events from New Physics in Icecube.
AB  - A variety of new physics models allows for neutrinos to up-scatter into heavier
      states. If the incident neutrino is energetic enough, the heavy neutrino may
      travel some distance before decaying. In this work, we consider the atmospheric
      neutrino flux as a source of such events. At IceCube, this would lead to a
      "double-bang" (DB) event topology, similar to what is predicted to occur for tau
      neutrinos at ultrahigh energies. The DB event topology has an extremely low
      background rate from coincident atmospheric cascades, making this a distinctive
      signature of new physics. Our results indicate that IceCube should already be
      able to derive new competitive constraints on models with GeV-scale sterile
      neutrinos using existing data.

PMID- 29219346
TI  - Angular Momentum of Topologically Structured Darkness.
AB  - We theoretically analyze and experimentally measure the extrinsic angular
      momentum contribution of topologically structured darkness found within
      fractional vortex beams, and show that this structured darkness can be explained
      by evanescent waves at phase discontinuities in the generating optic. We also
      demonstrate the first direct measurement of the intrinsic orbital angular
      momentum of light with both intrinsic and extrinsic angular momentum, and explain
      why the total orbital angular momenta of fractional vortices do not match the
      winding number of their generating phases.

PMID- 29219347
TI  - Long-Lived Inverse Chirp Signals from Core-Collapse in Massive Scalar-Tensor
      Gravity.
AB  - This Letter considers stellar core collapse in massive scalar-tensor theories of
      gravity. The presence of a mass term for the scalar field allows for dramatic
      increases in the radiated gravitational wave signal. There are several potential
      smoking gun signatures of a departure from general relativity associated with
      this process. These signatures could show up within existing LIGO-Virgo searches.

PMID- 29219348
TI  - Transition to Turbulent Dynamo Saturation.
AB  - While the saturated magnetic energy is independent of viscosity in dynamo
      experiments, it remains viscosity dependent in state-of-the-art 3D direct
      numerical simulations (DNS). Extrapolating such viscous scaling laws to realistic
      parameter values leads to an underestimation of the magnetic energy by several
      orders of magnitude. The origin of this discrepancy is that fully 3D DNS cannot
      reach low enough values of the magnetic Prandtl number Pm. To bypass this
      limitation and investigate dynamo saturation at very low Pm, we focus on the
      vicinity of the dynamo threshold in a rapidly rotating flow: the velocity field
      then depends on two spatial coordinates only, while the magnetic field consists
      of a single Fourier mode in the third direction. We perform numerical simulations
      of the resulting set of reduced equations for Pm down to 2*10^{-5}. This
      parameter regime is currently out of reach to fully 3D DNS. We show that the
      magnetic energy transitions from a high-Pm viscous scaling regime to a low-Pm
      turbulent scaling regime, the latter being independent of viscosity. The
      transition to the turbulent saturation regime occurs at a low value of the
      magnetic Prandtl number, Pm?10^{-3}, which explains why it has been overlooked by
      numerical studies so far.

PMID- 29219349
TI  - Time Scale for Adiabaticity Breakdown in Driven Many-Body Systems and
      Orthogonality Catastrophe.
AB  - The adiabatic theorem is a fundamental result in quantum mechanics, which states
      that a system can be kept arbitrarily close to the instantaneous ground state of
      its Hamiltonian if the latter varies in time slowly enough. The theorem has an
      impressive record of applications ranging from foundations of quantum field
      theory to computational molecular dynamics. In light of this success it is
      remarkable that a practicable quantitative understanding of what "slowly enough"
      means is limited to a modest set of systems mostly having a small Hilbert space.
      Here we show how this gap can be bridged for a broad natural class of physical
      systems, namely, many-body systems where a small move in the parameter space
      induces an orthogonality catastrophe. In this class, the conditions for
      adiabaticity are derived from the scaling properties of the parameter-dependent
      ground state without a reference to the excitation spectrum. This finding
      constitutes a major simplification of a complex problem, which otherwise requires
      solving nonautonomous time evolution in a large Hilbert space.

PMID- 29219350
TI  - Generation of Caustics and Rogue Waves from Nonlinear Instability.
AB  - Caustics are phenomena in which nature concentrates the energy of waves and may
      exhibit rogue-type behavior. Although they are known mostly in optics, caustics
      are intrinsic to all wave phenomena. As we demonstrate in this Letter, the
      formation of caustics and consequently rogue events in linear systems requires
      strong phase fluctuations. We show that nonlinear phase shifts can generate sharp
      caustics from even small fluctuations. Moreover, in that the wave amplitude
      increases dramatically in caustics, nonlinearity is usually inevitable. We
      perform an experiment in an optical system with Kerr nonlinearity, simulate the
      results based on the nonlinear Schrodinger equation, and achieve perfect
      agreement. As the same theoretical framework is used to describe other wave
      systems such as large-scale water waves, our results may also aid the
      understanding of ocean phenomena.

PMID- 29219351
TI  - Imaging Galactic Dark Matter with High-Energy Cosmic Neutrinos.
AB  - We show that the high-energy cosmic neutrinos seen by the IceCube Neutrino
      Observatory can be used to probe interactions between neutrinos and the dark
      sector that cannot be reached by current cosmological methods. The origin of the
      observed neutrinos is still unknown, and their arrival directions are compatible
      with an isotropic distribution. This observation, together with dedicated studies
      of Galactic plane correlations, suggests a predominantly extragalactic origin.
      Interactions between this isotropic extragalactic flux and the dense dark matter
      (DM) bulge of the Milky Way would thus lead to an observable imprint on the
      distribution, which would be seen by IceCube as (i) slightly suppressed fluxes at
      energies below a PeV and (ii) a deficit of events in the direction of the
      Galactic center. We perform an extended unbinned likelihood analysis using the
      four-year high-energy starting event data set to constrain the strength of DM
      neutrino interactions for two model classes. We find that, in spite of low
      statistics, IceCube can probe regions of the parameter space inaccessible to
      current cosmological methods.

PMID- 29219352
TI  - Probing Seesaw with Parity Restoration.
AB  - We present a novel way of testing the seesaw origin of neutrino mass in the
      context of the minimal left-right symmetric model. It is based on the connection
      between the leptonic interactions of the doubly charged scalars, whose presence
      is at the core of the seesaw mechanism, and the neutrino Dirac Yukawa couplings
      which govern, among other processes, the right-handed neutrino decays into left
      handed charged leptons. We prove that any physical quantity depending on these
      couplings is a function of the Hermitian part only, which can significantly
      simplify their future experimental determination.

PMID- 29219354
TI  - Bound States of Skyrmions and Merons near the Lifshitz Point.
AB  - We study topological defects in anisotropic ferromagnets with competing
      interactions near the Lifshitz point. We show that Skyrmions and bimerons are
      stable in a large part of the phase diagram. We calculate Skyrmion-Skyrmion and
      meron-meron interactions and show that Skyrmions attract each other and form ring
      shaped bound states in a zero magnetic field. At the Lifshitz point merons
      carrying a fractional topological charge become deconfined. These results imply
      that unusual topological excitations may exist in weakly frustrated magnets with
      conventional crystal lattices.

PMID- 29219355
TI  - Direct CP Violation in K->MU^{+}MU^{-}.
AB  - A rare decay K_{L}->MU^{+}MU^{-} has been measured precisely, while a rare decay
      K_{S}->MU^{+}MU^{-} will be observed by an upgrade of the LHCb experiment.
      Although both processes are almost CP-conserving decays, we point out that an
      interference contribution between K_{L} and K_{S} in the kaon beam emerges from a
      genuine direct CP violation. It is found that the interference contribution can
      change K_{S}->MU^{+}MU^{-} standard-model predictions at O(60%). We also stress
      that an unknown sign of A(K_{L}->gammagamma) can be determined by a measurement
      of the interference, which can much reduce a theoretical uncertainty of B(K_{L}
      >MU^{+}MU^{-}). We also investigate the interference in a new physics model,
      where the epsilon_{K}^{'}/epsilon_{K} tension is explained by an additional Z
      penguin contribution.

PMID- 29219356
TI  - Complete Mean-Field Theory for Dynamics of Binary Recurrent Networks.
AB  - We develop a unified theory that encompasses the macroscopic dynamics of
      recurrent interactions of binary units within arbitrary network architectures.
      Using the martingale theory, our mathematical analysis provides a complete
      description of nonequilibrium fluctuations in networks with a finite size and
      finite degree of interactions. Our approach allows the investigation of systems
      for which a deterministic mean-field theory breaks down. To demonstrate this, we
      uncover a novel dynamic state in which a recurrent network of binary units with
      statistically inhomogeneous interactions, along with an asynchronous behavior,
      also exhibits collective nontrivial stochastic fluctuations in the
      thermodynamical limit.

PMID- 29219357
TI  - Solvable Sachdev-Ye-Kitaev Models in Higher Dimensions: From Diffusion to Many
      Body Localization.
AB  - Many aspects of many-body localization (MBL) transitions remain elusive so far.
      Here, we propose a higher-dimensional generalization of the Sachdev-Ye-Kitaev
      (SYK) model and show that it exhibits a MBL transition. The model on a bipartite
      lattice has N Majorana fermions with SYK interactions on each site of the A
      sublattice and M free Majorana fermions on each site of the B sublattice, where N
      and M are large and finite. For r=M/N<r_{c}=1, it describes a diffusive metal
      exhibiting maximal chaos. Remarkably, its diffusive constant D vanishes [D?(r_{c}
      r)^{1/2}] as r->r_{c}, implying a dynamical transition to a MBL phase. It is
      further supported by numerical calculations of level statistics which changes
      from Wigner-Dyson (r<r_{c}) to Poisson (r>r_{c}) distributions. Note that no
      subdiffusive phase intervenes between diffusive and MBL phases. Moreover, the
      critical exponent nu=0, violating the Harris criterion. Our higher-dimensional
      SYK model may provide a promising arena to explore exotic MBL transitions.

PMID- 29219358
TI  - Digital Quantum Estimation.
AB  - Quantum metrology calculates the ultimate precision of all estimation strategies,
      measuring what is their root-mean-square error (RMSE) and their Fisher
      information. Here, instead, we ask how many bits of the parameter we can recover;
      namely, we derive an information-theoretic quantum metrology. In this setting, we
      redefine "Heisenberg bound" and "standard quantum limit" (the usual benchmarks in
      the quantum estimation theory) and show that the former can be attained only by
      sequential strategies or parallel strategies that employ entanglement among
      probes, whereas parallel-separable strategies are limited by the latter. We
      highlight the differences between this setting and the RMSE-based one.

PMID- 29219359
TI  - Probing Positron Cooling in Noble Gases via Annihilation gamma Spectra.
AB  - gamma spectra for positron annihilation in noble-gas atoms are calculated using
      many-body theory for positron momenta up to the positronium-formation threshold.
      These data are used, together with time-evolving positron-momentum distributions
      determined in the preceding Letter [Phys. Rev. Lett. 119, 203403 (2017)PRLTAO0031
      9007], to calculate the time-varying gamma spectra produced during positron
      cooling in noble gases. The gamma spectra and their S[over -] and W[over -] shape
      parameters are shown to be sensitive probes of the time evolution of the positron
      momentum distribution and thus provide a means of studying positron cooling that
      is complementary to positron lifetime spectroscopy.

PMID- 29219360
TI  - Positron Cooling and Annihilation in Noble Gases.
AB  - Positron cooling and annihilation in room temperature noble gases is simulated
      using accurate scattering and annihilation cross sections calculated with many
      body theory, enabling the first simultaneous probing of the energy dependence of
      the scattering and annihilation cross sections. A strikingly small fraction of
      positrons is shown to survive to thermalization: ~0.1 in He, ~0 in Ne, ~0.15 in
      Ar, ~0.05 in Kr, and ~0.01 in Xe. For Xe, the time-varying annihilation rate
      Z[over -]_{eff}(tau) is shown to be highly sensitive to the depletion of the
      momentum distribution due to annihilation, conclusively explaining the long
      standing discrepancy between gas-cell and trap-based measurements. Overall, the
      use of the accurate atomic data gives Z[over -]_{eff}(tau) in close agreement
      with experiment for all noble gases except Ne, the experiment for which is
      proffered to have suffered from incomplete knowledge of the fraction of positrons
      surviving to thermalization and/or the presence of impurities.

PMID- 29219361
TI  - Different Time Scales in the Dissociation Dynamics of Core-Excited CF_{4} by Two
      Internal Clocks.
AB  - Fragmentation processes following C 1s->lowest unoccupied molecular orbital core
      excitations in CF_{4} have been analyzed on the ground of the angular
      distribution of the CF_{3}^{+} emitted fragments by means of Auger electron
      photoion coincidences. Different time scales have been enlightened, which
      correspond to either ultrafast fragmentation, on the few-femtosecond scale, where
      the molecule has no time to rotate and the fragments are emitted according to the
      maintained orientation of the core-excited species, or dissociation after
      resonant Auger decay, where the molecule still keeps some memory of the
      excitation process before reassuming random orientation. Potential energy
      surfaces of the ground, core-excited, and final states have been calculated at
      the ab initio level, which show the dissociative nature of the neutral excited
      state, leading to ultrafast dissociation, as well as the also dissociative nature
      of some of the final ionic states reached after resonant Auger decay, yielding
      the same fragments on a much longer time scale.

PMID- 29219362
TI  - Multiple Types of Topological Fermions in Transition Metal Silicides.
AB  - Exotic massless fermionic excitations with nonzero Berry flux, other than the
      Dirac and Weyl fermions, could exist in condensed matter systems under the
      protection of crystalline symmetries, such as spin-1 excitations with threefold
      degeneracy and spin-3/2 Rarita-Schwinger-Weyl fermions. Herein, by using the ab
      initio density functional theory, we show that these unconventional
      quasiparticles coexist with type-I and type-II Weyl fermions in a family of
      transition metal silicides, including CoSi, RhSi, RhGe, and CoGe, when spin-orbit
      coupling is considered. Their nontrivial topology results in a series of
      extensive Fermi arcs connecting projections of these bulk excitations on the side
      surface, which is confirmed by (001) surface electronic spectra of CoSi. In
      addition, these stable arc states exist within a wide energy window around the
      Fermi level, which makes them readily accessible in angle-resolved photoemission
      spectroscopy measurements.

PMID- 29219363
TI  - Double-Exchange Interaction in Optically Induced Nonequilibrium State: A
      Conversion from Ferromagnetic to Antiferromagnetic Structure.
AB  - The double-exchange (DE) interaction, that is, a ferromagnetic (FM) interaction
      due to a combination of electron motion and the Hund coupling, is a well-known
      source of a wide class of FM orders. Here, we show that the DE interaction in
      highly photoexcited states is antiferromagnetic (AFM). Transient dynamics of
      quantum electrons coupled with classical spins are analyzed. An ac field applied
      to a metallic FM state results in an almost perfect Neel state. A time
      characterizing the FM-to-AFM conversion is scaled by light amplitude and
      frequency. This hidden AFM interaction is attributable to the electron-spin
      coupling under nonequilibrium electron distribution.

PMID- 29219353
TI  - Measurement of the D^{*}(2010)^{+}-D^{+} Mass Difference.
AB  - We measure the mass difference, Deltam_{+}, between the D^{*}(2010)^{+} and the
      D^{+} using the decay chain D^{*}(2010)^{+}->D^{+}pi^{0} with D^{+}->K^{
      }pi^{+}pi^{+}. The data were recorded with the BABAR detector at center-of-mass
      energies at and near the Upsilon(4S) resonance, and correspond to an integrated
      luminosity of approximately 468  fb^{-1}. We measure Deltam_{+}=(140 601.0+/
      6.8[stat]+/-12.9[syst])  keV. We combine this result with a previous BABAR
      measurement of Deltam_{0}=m(D^{*}(2010)^{+})-m(D^{0}) to obtain
      Deltam_{D}=m(D^{+})-m(D^{0})=(4824.9+/-6.8[stat]+/-12.9[syst])  keV. These
      results are compatible with and approximately five times more precise than the
      Particle Data Group averages.

PMID- 29219364
TI  - Lorentz Symmetry Violations from Matter-Gravity Couplings with Lunar Laser
      Ranging.
AB  - The standard-model extension (SME) is an effective field theory framework aiming
      at parametrizing any violation to the Lorentz symmetry (LS) in all sectors of
      physics. In this Letter, we report the first direct experimental measurement of
      SME coefficients performed simultaneously within two sectors of the SME framework
      using lunar laser ranging observations. We consider the pure gravitational sector
      and the classical point-mass limit in the matter sector of the minimal SME. We
      report no deviation from general relativity and put new realistic stringent
      constraints on LS violations improving up to 3 orders of magnitude previous
      estimations.

PMID- 29219365
TI  - Unconventional Chiral Fermions and Large Topological Fermi Arcs in RhSi.
AB  - The theoretical proposal of chiral fermions in topological semimetals has led to
      a significant effort towards their experimental realization. In particular, the
      Fermi surfaces of chiral semimetals carry quantized Chern numbers, making them an
      attractive platform for the observation of exotic transport and optical
      phenomena. While the simplest example of a chiral fermion in condensed matter is
      a conventional |C|=1 Weyl fermion, recent theoretical works have proposed a
      number of unconventional chiral fermions beyond the standard model which are
      protected by unique combinations of topology and crystalline symmetries. However,
      materials candidates for experimentally probing the transport and response
      signatures of these unconventional fermions have thus far remained elusive. In
      this Letter, we propose the RhSi family in space group No. 198 as the ideal
      platform for the experimental examination of unconventional chiral fermions. We
      find that RhSi is a filling-enforced semimetal that features near its Fermi
      surface a chiral double sixfold-degenerate spin-1 Weyl node at R and a previously
      uncharacterized fourfold-degenerate chiral fermion at Gamma. Each unconventional
      fermion displays Chern number +/-4 at the Fermi level. We also show that RhSi
      displays the largest possible momentum separation of compensative chiral
      fermions, the largest proposed topologically nontrivial energy window, and the
      longest possible Fermi arcs on its surface. We conclude by proposing signatures
      of an exotic bulk photogalvanic response in RhSi.

PMID- 29219366
TI  - Topological Edge-State Manifestation of Interacting 2D Condensed Boson-Lattice
      Systems in a Harmonic Trap.
AB  - In this Letter, it is shown that interactions can facilitate the emergence of
      topological edge states of quantum-degenerate bosonic systems in the presence of
      a harmonic potential. This effect is demonstrated with the concrete model of a
      hexagonal lattice populated by spin-one bosons under a synthetic gauge field. In
      fermionic or noninteracting systems, the presence of a harmonic trap can obscure
      the observation of edge states. For our system with weakly interacting bosons in
      the Thomas-Fermi regime, we can clearly see a topological band structure with a
      band gap traversed by edge states. We also find that the number of edge states
      crossing the gap is increased in the presence of a harmonic trap, and the edge
      modes experience an energy shift while traversing the first Brillouin zone which
      is related to the topological properties of the system. We find an analytical
      expression for the edge-state energies and our comparison with numerical
      computation shows excellent agreement.

PMID- 29219367
TI  - Superconductivity at the Polar-Nonpolar Phase Boundary of SnP with an Unusual
      Valence State.
AB  - Structural, magnetic, and electrical characterizations reveal that SnP with an
      unusual valence state (nominally Sn^{3+}) undergoes a ferroelectriclike
      structural transition from a simple NaCl-type structure to a polar tetragonal
      structure at approximately 250 K at ambient pressure. First-principles
      calculations indicate that the experimentally observed tetragonal distortion
      enhances the charge transfer from Sn to P, thereby making the polar tetragonal
      phase energetically more stable than the nonpolar cubic phase. Hydrostatic
      pressure is found to promptly suppress the structural phase transition in SnP,
      leading to the emergence of bulk superconductivity in a phase-competitive manner.
      These findings suggest that control of ferroelectriclike instability in a metal
      can be a promising way for creating novel superconductors.

PMID- 29219369
TI  - Polyatomic Trilobite Rydberg Molecules in a Dense Random Gas.
AB  - Trilobites are exotic giant dimers with enormous dipole moments. They consist of
      a Rydberg atom and a distant ground-state atom bound together by short-range
      electron-neutral attraction. We show that highly polar, polyatomic trilobite
      states unexpectedly persist and thrive in a dense ultracold gas of randomly
      positioned atoms. This is caused by perturbation-induced quantum scarring and the
      localization of electron density on randomly occurring atom clusters. At certain
      densities these states also mix with an s state, overcoming selection rules that
      hinder the photoassociation of ordinary trilobites.

PMID- 29219368
TI  - Satellite-to-Ground Entanglement-Based Quantum Key Distribution.
AB  - We report on entanglement-based quantum key distribution between a low-Earth
      orbit satellite equipped with a space borne entangled-photon source and a ground
      observatory. One of the entangled photons is measured locally at the satellite,
      and the other one is sent via a down link to the receiver in the Delingha ground
      station. The link attenuation is measured to vary from 29 dB at 530 km to 36 dB
      at 1000 km. We observe that the two-photon entanglement survives after being
      distributed between the satellite and the ground, with a measured state fidelity
      of >=0.86. We then perform the entanglement-based quantum key distribution
      protocol and obtain an average final key rate of 3.5  bits/s at the distance
      range of 530-1000 km.

PMID- 29219370
TI  - Visualization of Room-Temperature Ferroelectricity and Polarization Rotation in
      the Thin Film of Quinuclidinium Perrhenate.
AB  - Recently, a plastic crystal of quinuclidinium perrhenate (HQReO_{4}) was reported
      to have the feasibility of controlling the crystallographic orientation in the
      grown crystal, but the corresponding temperature window is only about 22 K (345
      367 K). Such a narrow window and uncertain ferroelectricity at room temperature
      would extremely limit its application potential. In this report, we prepared a
      large area high-quality polycrystalline thin film of HQReO_{4} and for the first
      time observed ferroelectricity in the temperature range from 298 to 367 K.
      Density functional theory calculations revealed the origin of room-temperature
      ferroelectricity is ascribed to the collaborative flipping of HQ (protonated
      quinuclidine) and ReO_{4}^{-}, which is dynamically preferred in the presence of
      a N?H?O hydrogen bond. A local piezoresponse force microscopy measurement was
      also employed to study the mechanisms of multiaxial polarization rotation and
      domain dynamics. By extending the ferroelectric temperature window to room
      temperature and the extraordinary thin-film processability, HQReO_{4} would
      certainly become a suitable candidate for next generation ferroelectric
      materials.

PMID- 29219371
TI  - Comparison Study of Strong-Field Ionization of Molecules and Atoms by Bicircular
      Two-Color Femtosecond Laser Pulses.
AB  - We experimentally investigate the single and double ionization of N_{2} and O_{2}
      molecules in bicircular two-color femtosecond laser pulses, and compare with
      their companion atoms of Ar and Xe with comparable ionization thresholds.
      Electron recollision assisted enhanced ionization is observed in N_{2} and Ar by
      controlling the helicity and field ratio between the two colors, whereas the
      enhanced ionization via the recollision is almost absent in O_{2} and Xe. Our S
      matrix simulations clearly reveal the crucial role of the detailed electronic
      structures of N_{2} and O_{2} on the two-dimensional recollision of the electrons
      driven by the bicircular two-color laser fields. As compared to Ar, the resonant
      multiphoton excitation dominates the double ionization of Xe.

PMID- 29219372
TI  - Flow of Deformable Droplets: Discontinuous Shear Thinning and Velocity
      Oscillations.
AB  - We study the rheology of a suspension of soft deformable droplets subjected to a
      pressure-driven flow. Through computer simulations, we measure the apparent
      viscosity as a function of droplet concentration and pressure gradient, and
      provide evidence of a discontinuous shear thinning behavior, which occurs at a
      concentration-dependent value of the forcing. We further show that this response
      is associated with a nonequilibrium transition between a "hard" (or less
      deformable) phase, which is nearly jammed and flows very slowly, and a "soft" (or
      more deformable) phase, which flows much more easily. The soft phase is
      characterized by flow-induced time dependent shape deformations and internal
      currents, which are virtually absent in the hard phase. Close to the transition,
      we find sustained oscillations in both the droplet and fluid velocities.
      Polydisperse systems show similar phenomenology but with a smoother transition,
      and less regular oscillations.

PMID- 29219373
TI  - Shakeoff Ionization near the Coulomb Barrier Energy.
AB  - We measure the projectile K x-ray spectra as a function of the beam energies
      around the Coulomb barrier in different collision systems. The energy is scanned
      in small steps around the barrier aiming to explore the nuclear effects on the
      elastically scattered projectile ions. The variation of the projectile x-ray
      energy with the ion-beam energies exhibits an unusual increase in between the
      interaction barrier and fusion barrier energies. This additional contribution to
      the projectile ionization can be attributed to the shakeoff of outer-shell
      electrons of the projectile ions due to the sudden nuclear recoil (~10^{-21} 
      sec) caused by the attractive nuclear potential, which gets switched on near the
      interaction barrier energy. In the sudden approximation limit, the theoretical
      shakeoff probability calculation due to the nuclear recoil explains the observed
      data well. In addition to its fundamental interest, such processes can play a
      significant role in dark matter detection through the possible mechanism of x-ray
      emissions, where the weakly interacting massive particle-nucleus elastic
      scattering can lead to the nuclear-recoil-induced inner-shell vacancy creations.
      Furthermore, the present work may provide new prospects for atomic physics
      research at barrier energies as well as provide a novel technique to perform
      barrier distribution studies for two-body systems.

PMID- 29219374
TI  - Band Structure and Contact Resistance of Carbon Nanotubes Deformed by a Metal
      Contact.
AB  - Capillary and van der Waals forces cause nanotubes to deform or even collapse
      under metal contacts. Using ab initio band structure calculations, we find that
      these deformations reduce the band gap by as much as 30%, while fully collapsed
      nanotubes become metallic. Moreover, degeneracy lifting due to the broken axial
      symmetry, and wave functions mismatch between the fully collapsed and the round
      portions of a CNT, lead to a 3 times higher contact resistance. The latter we
      demonstrate by contact resistance calculations within the tight-binding approach.

PMID- 29219375
TI  - Propagation Dynamics Associated with Resonant Magnetic Perturbation Fields in
      High-Confinement Mode Plasmas inside the KSTAR Tokamak.
AB  - The propagation dynamics of resonant magnetic perturbation fields in KSTAR H-mode
      plasmas with injection of small edge perturbations produced by a supersonic
      molecular beam injection is reported for the first time. The results show that
      the perturbation field first excites a plasma response on the q=3 magnetic
      surface and then propagates inward to the q=2 surface with a radially averaged
      propagation velocity of resonant magnetic perturbations field equal to 32.5  m/
      s. As a result, the perturbation field brakes the toroidal rotation on the q=3
      surface first causing a momentum transport perturbation that propagates both
      inward and outward. A higher density fluctuation level is observed. The
      propagation velocity of the resonant magnetic perturbations field is larger than
      the radial propagation velocity of the perturbation in the toroidal rotation.

PMID- 29219376
TI  - Absence of Marginal Stability in a Structural Glass.
AB  - Marginally stable solids have peculiar physical properties that were first
      analyzed in the context of the jamming transition. We theoretically investigate
      the existence of marginal stability in a prototypical model for structural glass
      formers, combining analytical calculations in infinite dimensions to computer
      simulations in three dimensions. While mean-field theory predicts the existence
      of a Gardner phase transition towards a marginally stable glass phase at low
      temperatures, simulations show no hint of diverging time scales or length scales,
      but reveal instead the presence of sparse localized defects. Our results suggest
      that the Gardner transition is deeply affected by finite dimensional
      fluctuations, and raise issues about the relevance of marginal stability in
      structural glasses far away from jamming.

PMID- 29219377
TI  - Stacking Characteristics of Close Packed Materials.
AB  - It is shown that the enthalpy of any close packed structure for a given element
      can be characterized as a linear expansion in a set of continuous variables
      alpha_{n}, which describe the stacking configuration. This enables us to
      represent the infinite, discrete set of stacking sequences within a finite,
      continuous space of the expansion parameters H_{n}. These H_{n} determine the
      stable structure and vary continuously in the thermodynamic space of pressure,
      temperature, or composition. The continuity of both spaces means that only
      transformations between stable structures adjacent in the H_{n} space are
      possible, giving the model predictive as well as descriptive ability. We
      calculate the H_{n} using density functional theory (DFT)and interatomic
      potentials for a range of materials. Some striking results are found: e.g., the
      Lennard-Jones potential model has 11 possible stable structures and over 50 phase
      transitions as a function of cutoff range. The very different phase diagrams of
      Sc, Tl, Y, and the lanthanides are understood within a single theory. We find
      that the widely reported 9R-fcc transition is not allowed in equilibrium
      thermodynamics, and in cases where it has been reported in experiments (Li, Na),
      we show that DFT theory is also unable to predict it.

PMID- 29219378
TI  - Lattice Model to Derive the Fluctuating Hydrodynamics of Active Particles with
      Inertia.
AB  - We derive the hydrodynamic equations with fluctuating currents for the density,
      momentum, and energy fields for an active system in the dilute limit. In our
      model, nonoverdamped self-propelled particles (such as grains or birds) move on a
      lattice, interacting by means of aligning dissipative forces and excluded volume
      repulsion. Our macroscopic equations, in a specific case, reproduce a transition
      line from a disordered phase to a swarming phase and a linear dispersion law
      accounting for underdamped wave propagation. Numerical simulations up to a
      packing fraction ~10% are in fair agreement with the theory, including the
      macroscopic noise amplitudes. At a higher packing fraction, a dense-diluted
      coexistence emerges. We underline the analogies with the granular kinetic
      theories, elucidating the relation between the active swarming phase and granular
      shear instability.

PMID- 29219379
TI  - Optimizing Hyperuniformity in Self-Assembled Bidisperse Emulsions.
AB  - We study long range density fluctuations (hyperuniformity) in two-dimensional
      jammed packings of bidisperse droplets. Taking advantage of microfluidics, we
      systematically span a large range of size and concentration ratios of the two
      droplet populations. We identify various defects increasing long range density
      fluctuations mainly due to organization of local particle environment. By
      choosing an appropriate bidispersity, we fabricate materials with a high level of
      hyperuniformity. Interesting transparency properties of these optimized materials
      are established based on numerical simulations.

PMID- 29219380
TI  - Generating Carrier-Envelope-Phase Stabilized Few-Cycle Pulses from a Free
      Electron Laser Oscillator.
AB  - We propose a scheme to generate carrier-envelope-phase (CEP) stabilized few-cycle
      optical pulses from a free-electron laser oscillator. The CEP stabilization is
      realized by the continuous injection of CEP-stabilized seed pulses from an
      external laser to the free-electron laser oscillator whose cavity length is
      perfectly synchronized to the electron bunch repetition. Operated at a
      midinfrared wavelength, the proposed method is able to drive a photon source
      based on high harmonic generation (HHG) to explore the generation of isolated
      attosecond pulses at photon energies above 1 keV with a repetition of >10  MHz.
      The HHG photon source will open a door to full-scale experiments of attosecond x
      ray pulses and push ultrafast laser science to the zeptosecond regime.

PMID- 29219381
TI  - Geiger-Nuttall Law for Nuclei in Strong Electromagnetic Fields.
AB  - We investigate the influence of a strong laser electromagnetic field on the alpha
      decay rate by using the Hennenberger frame of reference. We introduce an
      adimensional parameter D=S_{0}/R_{0}, where R_{0} is the geometrical nuclear
      radius and S_{0}~sqrt[I]/omega^{2} is a length parameter depending on the laser
      intensity I and frequency omega. We show that the barrier penetrability has a
      strong increase for intensities corresponding to D>D_{crit}=1, due to the fact
      that the resulting Coulomb potential becomes strongly anisotropic even for
      spherical nuclei. As a consequence, the contribution of the monopole term
      increases the barrier penetrability by 2 orders of magnitude, while the total
      contribution has an effect of 6 orders of magnitude at D~3D_{crit}. In the case
      of deformed nuclei, the electromagnetic field increases the penetrability by an
      additional order of magnitude for a quadrupole deformation beta_{2}~0.3. The
      influence of the electromagnetic field can be expressed in terms of a shifted
      Geiger-Nuttal law by a term depending on S_{0} and deformation.

PMID- 29219382
TI  - Optimal Design of Experiments by Combining Coarse and Fine Measurements.
AB  - In many contexts, it is extremely costly to perform enough high-quality
      experimental measurements to accurately parametrize a predictive quantitative
      model. However, it is often much easier to carry out large numbers of experiments
      that indicate whether each sample is above or below a given threshold. Can many
      such categorical or "coarse" measurements be combined with a much smaller number
      of high-resolution or "fine" measurements to yield accurate models? Here, we
      demonstrate an intuitive strategy, inspired by statistical physics, wherein the
      coarse measurements are used to identify the salient features of the data, while
      the fine measurements determine the relative importance of these features. A
      linear model is inferred from the fine measurements, augmented by a quadratic
      term that captures the correlation structure of the coarse data. We illustrate
      our strategy by considering the problems of predicting the antimalarial potency
      and aqueous solubility of small organic molecules from their 2D molecular
      structure.

PMID- 29219384
TI  - Discovery of the Doubly Charmed Xi_{cc} Baryon Implies a Stable bbu[over -]d[over
      -] Tetraquark.
AB  - Recently, the LHCb Collaboration discovered the first doubly charmed baryon
      Xi_{cc}^{++}=ccu at 3621.40+/-0.78  MeV, very close to our theoretical
      prediction. We use the same methods to predict a doubly bottom tetraquark
      T(bbu[over -]d[over -]) with J^{P}=1^{+} at 10 389+/-12  MeV, 215 MeV below the
      B^{-}B[over -]^{*0} threshold and 170 MeV below the threshold for decay to B^{
      }B[over -]^{0}gamma. The T(bbu[over -]d[over -]) is therefore stable under strong
      and electromagnetic interactions and can only decay weakly, the first exotic
      hadron with such a property. On the other hand, the mass of T(ccu[over -]d[over 
      ]) with J^{P}=1^{+} is predicted to be 3882+/-12  MeV, 7 MeV above the
      D^{0}D^{*+} threshold and 148 MeV above the D^{0}D^{+}gamma threshold. T(bcu[over
      -]d[over -]) with J^{P}=0^{+} is predicted at 7134+/-13  MeV, 11 MeV below the
      B[over -]^{0}D^{0} threshold. Our precision is not sufficient to determine
      whether bcu[over -]d[over -] is actually above or below the threshold. It could
      manifest itself as a narrow resonance just at threshold.

PMID- 29219383
TI  - Wall Slip of Soft-Jammed Systems: A Generic Simple Shear Process.
AB  - From well-controlled long creep tests, we show that the residual apparent yield
      stress observed with soft-jammed systems along smooth surfaces is an artifact due
      to edge effects. By removing these effects, we can determine the stress solely
      associated with steady-state wall slip below the material yield stress. This
      stress is found to vary linearly with the slip velocity for a wide range of
      materials whatever the structure, the interaction types between the elements and
      with the wall, and the concentration. Thus, wall slip results from the laminar
      flow of some given free liquid volume remaining between the (rough) jammed
      structure formed by the elements and the smooth wall. This phenomenon may be
      described by the simple shear flow in a Newtonian liquid layer of uniform
      thickness. For various systems, this equivalent thickness varies in a narrow
      range (35+/-15  nm).

PMID- 29219385
TI  - Magnetospheric Multiscale Observation of Plasma Velocity-Space Cascade: Hermite
      Representation and Theory.
AB  - Plasma turbulence is investigated using unprecedented high-resolution ion
      velocity distribution measurements by the Magnetospheric Multiscale mission (MMS)
      in the Earth's magnetosheath. This novel observation of a highly structured
      particle distribution suggests a cascadelike process in velocity space. Complex
      velocity space structure is investigated using a three-dimensional Hermite
      transform, revealing, for the first time in observational data, a power-law
      distribution of moments. In analogy to hydrodynamics, a Kolmogorov approach leads
      directly to a range of predictions for this phase-space transport. The scaling
      theory is found to be in agreement with observations. The combined use of state
      of-the-art MMS data sets, novel implementation of a Hermite transform method, and
      scaling theory of the velocity cascade opens new pathways to the understanding of
      plasma turbulence and the crucial velocity space features that lead to
      dissipation in plasmas.

PMID- 29219386
TI  - Persistence and Lifelong Fidelity of Phase Singularities in Optical Random Waves.
AB  - Phase singularities are locations where light is twisted like a corkscrew, with
      positive or negative topological charge depending on the twisting direction.
      Among the multitude of singularities arising in random wave fields, some can be
      found at the same location, but only when they exhibit opposite topological
      charge, which results in their mutual annihilation. New pairs can be created as
      well. With near-field experiments supported by theory and numerical simulations,
      we study the persistence and pairing statistics of phase singularities in random
      optical fields as a function of the excitation wavelength. We demonstrate how
      such entities can encrypt fundamental properties of the random fields in which
      they arise.

PMID- 29219387
TI  - Four-Loop Nonplanar Cusp Anomalous Dimension in N=4 Supersymmetric Yang-Mills
      Theory.
AB  - The lightlike cusp anomalous dimension is a universal function that controls
      infrared divergences in quite general gauge theories. In the maximally
      supersymmetric Yang-Mills theory this function is fixed fully by integrability to
      the three-loop order. At four loops a nonplanar correction appears which we
      obtain for the first time from a numerical computation of the Sudakov form
      factor. Key ingredients are widely applicable methods to control the number
      theoretic aspects of the appearing integrals. Our result shows explicitly that
      quadratic Casimir scaling breaks down at four loops.

PMID- 29219388
TI  - Observation of Broad d-Wave Feshbach Resonances with a Triplet Structure.
AB  - High partial-wave (l>=2) Feshbach resonance (FR) in an ultracold mixture of
      ^{85}Rb-^{87}Rb atoms is investigated experimentally aided by a partial-wave
      insensitive analytic multichannel quantum-defect theory. Two "broad" resonances
      from coupling between d waves in both the open and closed channels are observed
      and characterized. One of them shows a fully resolved triplet structure with a
      splitting ratio well explained by the perturbation to the closed channel due to
      interatomic spin-spin interaction. These tunable "broad" d-wave resonances,
      especially the one in the lowest-energy open channel, could find important
      applications in simulating d-wave coupling dominated many-body systems. In
      addition, we find that there is generally a time and temperature requirement,
      associated with tunneling through the angular momentum barrier, to establish and
      observe resonant coupling in nonzero partial waves.

PMID- 29219389
TI  - Mode Matching for Optical Antennas.
AB  - The emission rate of a point dipole can be strongly increased in the presence of
      a well-designed optical antenna. Yet, optical antenna design is largely based on
      radio-frequency rules, ignoring, e.g., Ohmic losses and non-negligible field
      penetration in metals at optical frequencies. Here, we combine reciprocity and
      Poynting's theorem to derive a set of optical-frequency antenna design rules for
      benchmarking and optimizing the performance of optical antennas driven by single
      quantum emitters. Based on these findings a novel plasmonic cavity antenna design
      is presented exhibiting a considerably improved performance compared to a
      reference two-wire antenna. Our work will be useful for the design of high
      performance optical antennas and nanoresonators for diverse applications ranging
      from quantum optics to antenna-enhanced single-emitter spectroscopy and sensing.

PMID- 29219390
TI  - Inductive Spikes in the Crab Nebula: A Theory of gamma-Ray Flares.
AB  - We show that the mysterious, rapidly variable emission at ~400  MeV observed from
      the Crab Nebula by the AGILE and Fermi satellites could be the result of a sudden
      drop in the mass loading of the pulsar wind. The current required to maintain
      wave activity in the wind is then carried by very few particles of a high Lorentz
      factor. On impacting the nebula, these particles produce a tightly beamed, high
      luminosity burst of hard gamma rays, similar to those observed. This implies that
      (i) the emission is synchrotron radiation in the toroidal field of the nebula
      and, therefore, linearly polarized and (ii) this mechanism potentially
      contributes to the gamma-ray emission from other powerful pulsars, such as the
      Magellanic Cloud objects J0537-6910 and B0540-69.

PMID- 29219391
TI  - Observation of Bogoliubov Band Hybridization in the Optimally Doped Trilayer
      Bi_{2}Sr_{2}Ca_{2}Cu_{3}O_{10+delta}.
AB  - Using a laser-excited angle-resolved photoemission spectroscopy capable of bulk
      sensitive and high-energy resolution measurements, we reveal a new phenomenon of
      superconductors in the optimally doped trilayer
      Bi_{2}Sr_{2}Ca_{2}Cu_{3}O_{10+delta}. We observe a hybridization of the
      Bogoliubov bands derived from the inner and outer CuO_{2} planes with different
      magnitudes of energy gaps. Our data clearly exhibit the splitting of coherent
      peaks and the consequent enhancement of spectral gaps. These features are
      reproduced by model calculations, which indicate that the gap enhancement extends
      over a wide range of Fermi surface up to the antinode. The significant modulation
      of electron pairing uncovered here might be a crucial factor to achieve the
      highest critical temperature in the trilayer cuprates.

PMID- 29219392
TI  - Superfluid Filaments of Dipolar Bosons in Free Space.
AB  - We systematically investigate the zero temperature phase diagram of bosons
      interacting via dipolar interactions in three dimensions in free space via path
      integral Monte Carlo simulations with a few hundreds of particles and periodic
      boundary conditions based on the worm algorithm. Upon increasing the strength of
      the dipolar interaction and at sufficiently high densities we find a wide region
      where filaments are stabilized along the direction of the external field. Most
      interestingly by computing the superfluid fraction we conclude that the
      superfluidity is anisotropic and is greatly suppressed along the orthogonal
      plane. Finally, we perform simulations at finite temperature confirming the
      stability of the filaments against thermal fluctuations and provide an estimate
      of the superfluid fraction in the weak coupling limit in the framework of the
      Landau two-fluid model.

PMID- 29219393
TI  - Topological Edge States in Periodically Driven Trapped-Ion Chains.
AB  - Topological insulating phases are primarily associated with condensed-matter
      systems, which typically feature short-range interactions. Nevertheless, many
      realizations of quantum matter can exhibit long-range interactions, and it is
      still largely unknown the effect that these latter may exert upon the topological
      phases. In this Letter, we investigate the Su-Schrieffer-Heeger topological
      insulator in the presence of long-range interactions. We show that this model can
      be readily realized in quantum simulators with trapped ions by means of a
      periodic driving. Our results indicate that the localization of the associated
      edge states is enhanced by the long-range interactions, and that the localized
      components survive within the ground state of the model. These effects could be
      easily confirmed in current state-of-the-art experimental implementations.

PMID- 29219394
TI  - Asymptotic Safety Guaranteed in Supersymmetry.
AB  - We explain how asymptotic safety arises in four-dimensional supersymmetric gauge
      theories. We provide asymptotically safe supersymmetric gauge theories together
      with their superconformal fixed points, R charges, phase diagrams, and UV-IR
      connecting trajectories. Strict perturbative control is achieved in a Veneziano
      limit. Consistency with unitarity and the a theorem is established. We find that
      supersymmetry enhances the predictivity of asymptotically safe theories.

PMID- 29219395
TI  - Unified Description of Dynamics of a Repulsive Two-Component Fermi Gas.
AB  - We study a binary spin mixture of a zero-temperature repulsively interacting
      ^{6}Li atoms using both the atomic-orbital and density-functional approaches. The
      gas is initially prepared in a configuration of two magnetic domains and we
      determine the frequency of the spin-dipole oscillations which are emerging after
      the repulsive barrier, initially separating the domains, is removed. We find, in
      agreement with recent experiment [G. Valtolina et al., Nat. Phys. 13, 704
      (2017)NPAHAX1745-247310.1038/nphys4108], the occurrence of a ferromagnetic
      instability in an atomic gas while the interaction strength between different
      spin states is increased, after which the system becomes ferromagnetic. The
      ferromagnetic instability is preceded by the softening of the spin-dipole mode.

PMID- 29219396
TI  - What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of
      Interfacial Hydrodynamics.
AB  - Thermo-osmotic and related thermophoretic phenomena can be found in many
      situations from biology to colloid science, but the underlying molecular
      mechanisms remain largely unexplored. Using molecular dynamics simulations, we
      measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic
      routes, for different solid-liquid interfacial energies. The simulations reveal,
      in particular, the crucial role of nanoscale interfacial hydrodynamics. For
      nonwetting surfaces, thermo-osmotic transport is largely amplified by
      hydrodynamic slip at the interface. For wetting surfaces, the position of the
      hydrodynamic shear plane plays a key role in determining the amplitude and sign
      of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic
      response of the water-graphene interface, which we relate to the very low
      interfacial friction displayed by this system. These results open new
      perspectives for the design of efficient functional interfaces for, e.g., waste
      heat harvesting.

PMID- 29219397
TI  - Thermodynamic Evidence for the Fulde-Ferrell-Larkin-Ovchinnikov State in the
      KFe_{2}As_{2} Superconductor.
AB  - We investigate the magnetic phase diagram near the upper critical field of
      KFe_{2}As_{2} by magnetic torque and specific heat experiments using a high
      resolution piezorotary positioner to precisely control the parallel alignment of
      the magnetic field with respect to the FeAs layers. We observe a clear double
      transition when the field is strictly aligned in the plane and a characteristic
      upturn of the upper critical field line, which goes far beyond the Pauli limit at
      4.8 T. This provides firm evidence that a Fulde-Ferrell-Larkin-Ovchinnikov state
      exists in this iron-based KFe_{2}As_{2} superconductor.

PMID- 29219398
TI  - Threshold and Jet Radius Joint Resummation for Single-Inclusive Jet Production.
AB  - We present the first threshold and jet radius jointly resummed cross section for
      single-inclusive hadronic jet production. We work at next-to-leading logarithmic
      accuracy and our framework allows for a systematic extension beyond the currently
      achieved precision. Long-standing numerical issues are overcome by performing the
      resummation directly in momentum space within soft collinear effective theory. We
      present the first numerical results for the LHC and observe an improved
      description of the available data. Our results are of immediate relevance for LHC
      precision phenomenology including the extraction of parton distribution functions
      and the QCD strong coupling constant.

PMID- 29219399
TI  - Erratum: Resonance Effects in Photoemission Time Delays [Phys. Rev. Lett. 115,
      133001 (2015)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.115.133001.

PMID- 29219400
TI  - State-of-the-Art Calculation of the Decay Rate of Electroweak Vacuum in the
      Standard Model.
AB  - The decay rate of the electroweak (EW) vacuum is calculated in the framework of
      the standard model (SM) of particle physics, using the recent progress in the
      understanding of the decay rate of metastable vacuum in gauge theories. We give a
      manifestly gauge-invariant expression of the decay rate. We also perform a
      detailed numerical calculation of the decay rate. With the best-fit values of the
      SM parameters, we find that the decay rate of the EW vacuum per unit volume is
      about 10^{-554}  Gyr^{-1} Gpc^{-3}; with the uncertainty in the top mass, the
      decay rate is estimated as 10^{-284}-10^{-1371}  Gyr^{-1} Gpc^{-3}.

PMID- 29219401
TI  - Dynamical Negative Differential Resistance in Antiferromagnetically Coupled Few
      Atom Spin Chains.
AB  - We present the appearance of negative differential resistance (NDR) in spin
      dependent electron transport through a few-atom spin chain. A chain of three
      antiferromagnetically coupled Fe atoms (Fe trimer) was positioned on a
      Cu_{2}N/Cu(100) surface and contacted with the spin-polarized tip of a scanning
      tunneling microscope, thus coupling the Fe trimer to one nonmagnetic and one
      magnetic lead. Pronounced NDR appears at the low bias of 7 mV, where inelastic
      electron tunneling dynamically locks the atomic spin in a long-lived excited
      state. This causes a rapid increase of the magnetoresistance between the spin
      polarized tip and Fe trimer and quenches elastic tunneling. By varying the
      coupling strength between the tip and Fe trimer, we find that in this transport
      regime the dynamic locking of the Fe trimer competes with magnetic exchange
      interaction, which statically forces the Fe trimer into its high
      magnetoresistance state and removes the NDR.

PMID- 29219402
TI  - Microphase Separation in Oil-Water Mixtures Containing Hydrophilic and
      Hydrophobic Ions.
AB  - We develop a lattice-based Monte Carlo simulation method for charged mixtures
      capable of treating dielectric heterogeneities. Using this method, we study oil
      water mixtures containing an antagonistic salt, with hydrophilic cations and
      hydrophobic anions. Our simulations reveal several phases with a spatially
      modulated solvent composition, in which the ions partition between water-rich and
      water-poor regions according to their affinity. In addition to the recently
      observed lamellar phase, we find tubular and droplet phases, reminiscent of those
      found in block copolymers and surfactant systems. Interestingly, these structures
      stem from ion-mediated interactions, which allows for tuning of the phase
      behavior via the concentrations, the ionic properties, and the temperature.

PMID- 29219403
TI  - Quantum Critical Behavior of One-Dimensional Soft Bosons in the Continuum.
AB  - We consider a zero-temperature one-dimensional system of bosons interacting via
      the soft-shoulder potential in the continuum, typical of dressed Rydberg gases.
      We employ quantum Monte Carlo simulations, which allow for the exact calculation
      of imaginary-time correlations, and a stochastic analytic continuation method, to
      extract the dynamical structure factor. At finite densities, in the weakly
      interacting homogeneous regime, a rotonic spectrum marks the tendency to
      clustering. With strong interactions, we indeed observe cluster liquid phases
      emerging, characterized by the spectrum of a composite harmonic chain. Luttinger
      theory has to be adapted by changing the reference lattice density field. In both
      the liquid and cluster liquid phases, we find convincing evidence of a secondary
      mode, which becomes gapless only at the transition. In that region, we also
      measure the central charge and observe its increase towards c=3/2, as recently
      evaluated in a related extended Bose-Hubbard model, and we note a fast reduction
      of the Luttinger parameter. For two-particle clusters, we then interpret such
      observations in terms of the compresence of a Luttinger liquid and a critical
      transverse Ising model, related to the instability of the reference lattice
      density field towards coalescence of sites, typical of potentials which are flat
      at short distances. Even in the absence of a true lattice, we are able to
      evaluate the spatial correlation function of a suitable pseudospin operator,
      which manifests ferromagnetic order in the cluster liquid phase, exponential
      decay in the liquid phase, and algebraic order at criticality.

PMID- 29219404
TI  - Revealing the Topology of Quasicrystals with a Diffraction Experiment.
AB  - Topological properties of crystals and quasicrystals is a subject of recent and
      growing interest. This Letter reports an experiment where, for certain
      quasicrystals, these properties can be directly retrieved from diffraction. We
      directly observe, using an interferometric approach, all of the topological
      invariants of finite-length Fibonacci chains in their diffraction pattern. We
      also quantitatively demonstrate the stability of these topological invariants
      with respect to structural disorder.

PMID- 29219405
TI  - Cavity QED Engineering of Spin Dynamics and Squeezing in a Spinor Gas.
AB  - We propose a method for engineering spin dynamics in ensembles of integer-spin
      atoms confined within a high-finesse optical cavity. Our proposal uses cavity
      assisted Raman transitions to engineer a Dicke model for integer-spin atoms,
      which, in a dispersive limit, reduces to effective atom-atom interactions within
      the ensemble. This scheme offers a promising and flexible new avenue for the
      exploration of a wide range of spinor many-body physics. As an example of this,
      we present results showing that this method can be used to generate spin-nematic
      squeezing in an ensemble of spin-1 atoms. With realistic parameters, the scheme
      should enable substantial squeezing on time scales much shorter than current
      experiments with spin-1 Bose-Einstein condensates.

PMID- 29219406
TI  - Efficient Low-Order Approximation of First-Passage Time Distributions.
AB  - We consider the problem of computing first-passage time distributions for
      reaction processes modeled by master equations. We show that this generally
      intractable class of problems is equivalent to a sequential Bayesian inference
      problem for an auxiliary observation process. The solution can be approximated
      efficiently by solving a closed set of coupled ordinary differential equations
      (for the low-order moments of the process) whose size scales with the number of
      species. We apply it to an epidemic model and a trimerization process and show
      good agreement with stochastic simulations.

PMID- 29219407
TI  - Horava Gravity is Asymptotically Free in 2+1 Dimensions.
AB  - We compute the beta functions of marginal couplings in projectable Horava gravity
      in 2+1 spacetime dimensions. We show that the renormalization group flow has an
      asymptotically free fixed point in the ultraviolet (UV), establishing the theory
      as a UV-complete model with dynamical gravitational degrees of freedom.
      Therefore, this theory may serve as a toy model to study fundamental aspects of
      quantum gravity. Our results represent a step forward towards understanding the
      UV properties of realistic versions of Horava gravity.

PMID- 29219408
TI  - Magnetic Exchange Interactions in the Molecular Nanomagnet Mn_{12}.
AB  - The discovery of magnetic bistability in Mn_{12} more than 20 years ago marked
      the birth of molecular magnetism, an extremely fertile interdisciplinary field
      and a powerful route to create tailored magnetic nanostructures. However, the
      difficulty to determine interactions in complex polycentric molecules often
      prevents their understanding. Mn_{12} is an outstanding example of this
      difficulty: although it is the forefather and most studied of all molecular
      nanomagnets, an unambiguous determination of even the leading magnetic exchange
      interactions is still lacking. Here we exploit four-dimensional inelastic neutron
      scattering to portray how individual spins fluctuate around the magnetic ground
      state, thus fixing the exchange couplings of Mn_{12} for the first time. Our
      results demonstrate the power of four-dimensional inelastic neutron scattering as
      an unrivaled tool to characterize magnetic clusters.

PMID- 29219409
TI  - Z_{3} Parafermionic Zero Modes without Andreev Backscattering from the 2/3
      Fractional Quantum Hall State.
AB  - Parafermionic zero modes are a novel set of excitations displaying non-Abelian
      statistics somewhat richer than that of Majorana modes. These modes are predicted
      to occur when nearby fractional quantum Hall edge states are gapped by an
      interposed superconductor. Despite substantial experimental progress, we argue
      that the necessary crossed Andreev reflection in this arrangement is a
      challenging milestone to reach. We propose a superconducting quantum dot array
      structure on a fractional quantum Hall edge that can lead to parafermionic zero
      modes from coherent superconducting forward scattering on a quantum Hall edge.
      Such coherent forward scattering has already been demonstrated in recent
      experiments. We show that for a spin-singlet superconductor interacting with
      loops of spin unpolarized 2/3 fractional quantum edge, even an array size of
      order 10 should allow one to systematically tune into a parafermionic degeneracy.

PMID- 29219410
TI  - Instabilities of Jammed Packings of Frictionless Spheres Under Load.
AB  - We consider the contribution to the density of vibrational states and the
      distribution of energy barrier heights of incipient instabilities in a glass
      modeled by a jammed packing of spheres. On approaching an instability, the
      frequency of a normal mode and the height of the energy barrier to cross into a
      new ground state both vanish. These instabilities produce a contribution to the
      density of vibrational states that scales as omega^{3} at low frequencies omega,
      and a contribution to the distribution of energy barriers DeltaH that scales as
      DeltaH^{-1/3} at low barrier heights.

PMID- 29219411
TI  - Three Dimensional Photonic Dirac Points in Metamaterials.
AB  - Topological semimetals, representing a new topological phase that lacks a full
      band gap in bulk states and exhibiting nontrivial topological orders, recently
      have been extended to photonic systems, predominantly in photonic crystals and to
      a lesser extent metamaterials. Photonic crystal realizations of Dirac
      degeneracies are protected by various space symmetries, where Bloch modes span
      the spin and orbital subspaces. Here, we theoretically show that Dirac points can
      also be realized in effective media through the intrinsic degrees of freedom in
      electromagnetism under electromagnetic duality. A pair of spin-polarized Fermi
      arc-like surface states is observed at the interface between air and the Dirac
      metamaterials. Furthermore, eigenreflection fields show the decoupling process
      from a Dirac point to two Weyl points. We also find the topological correlation
      between a Dirac point and vortex or vector beams in classical photonics. The
      experimental feasibility of our scheme is demonstrated by designing a realistic
      metamaterial structure. The theoretical proposal of the photonic Dirac point lays
      the foundation for unveiling the connection between intrinsic physics and global
      topology in electromagnetism.

PMID- 29219412
TI  - Nonlocal Entanglement of 1D Thermal States Induced by Fermion Exchange
      Statistics.
AB  - When two identical fermions exchange their positions, their wave function gains a
      phase factor of -1. We show that this distance-independent effect can induce
      nonlocal entanglement in one-dimensional (1D) electron systems having Majorana
      fermions at the ends. It occurs in the system bulk and has a nontrivial
      temperature dependence. In a system having a single Majorana fermion at each end,
      the nonlocal entanglement has a Bell-state form at zero temperature and decays as
      the temperature increases, vanishing suddenly at a certain finite temperature. In
      a system having two Majorana fermions at each end, it is in a cluster-state form
      and its nonlocality is more noticeable at a finite temperature. By contrast, the
      thermal states of corresponding 1D spins do not have nonlocal entanglement.

PMID- 29219413
TI  - Probing Sub-GeV Mass Strongly Interacting Dark Matter with a Low-Threshold
      Surface Experiment.
AB  - Using data from the nu-cleus detector, based on the surface of Earth, we place
      constraints on dark matter in the form of strongly interacting massive particles
      (SIMPs) which interact with nucleons via nuclear-scale cross sections. For large
      SIMP-nucleon cross sections, the sensitivity of traditional direct dark matter
      searches using underground experiments is limited by the energy loss experienced
      by SIMPs, due to scattering with the rock overburden and experimental shielding
      on their way to the detector apparatus. Hence, a surface-based experiment is
      ideal for a SIMP search, despite the much larger background resulting from the
      lack of shielding. We show using data from a recent surface run of a low
      threshold cryogenic detector that values of the SIMP-nucleon cross section up to
      approximately 10^{-27}  cm^{2} can be excluded for SIMPs with masses above 100
      MeV.

PMID- 29219414
TI  - Double Contact During Drop Impact on a Solid Under Reduced Air Pressure.
AB  - Drops impacting on solid surfaces entrap small bubbles under their centers, owing
      to the lubrication pressure which builds up in the thin intervening air layer. We
      use ultrahigh-speed interference imaging, at 5 Mfps, to investigate how this air
      layer changes when the ambient air pressure is reduced below atmospheric. Both
      the radius and the thickness of the air disc become smaller with reduced air
      pressure. Furthermore, we find the radial extent of the air disc bifurcates, when
      the compressibility parameter exceeds ~25. This bifurcation is also imprinted
      onto some of the impacts, as a double contact. In addition to the central air
      disc inside the first ring contact, this is immediately followed by a second ring
      contact, which entraps an outer toroidal strip of air, which contracts into a
      ring of bubbles. We find this occurs in a regime where Navier slip, due to
      rarefied gas effects, enhances the rate gas can escape from the path of the
      droplet.

PMID- 29219415
TI  - Strongly Correlated Metal Built from Sachdev-Ye-Kitaev Models.
AB  - Prominent systems like the high-T_{c} cuprates and heavy fermions display
      intriguing features going beyond the quasiparticle description. The Sachdev-Ye
      Kitaev (SYK) model describes a (0+1)D quantum cluster with random all-to-all four
      fermion interactions among N fermion modes which becomes exactly solvable as N
      >infinity, exhibiting a zero-dimensional non-Fermi-liquid with emergent conformal
      symmetry and complete absence of quasiparticles. Here we study a lattice of
      complex-fermion SYK dots with random intersite quadratic hopping. Combining the
      imaginary time path integral with real time path integral formulation, we obtain
      a heavy Fermi liquid to incoherent metal crossover in full detail, including
      thermodynamics, low temperature Landau quasiparticle interactions, and both
      electrical and thermal conductivity at all scales. We find linear in temperature
      resistivity in the incoherent regime, and a Lorentz ratio L=(kapparho/T) varies
      between two universal values as a function of temperature. Our work exemplifies
      an analytically controlled study of a strongly correlated metal.

PMID- 29219416
TI  - Glassy Anomalies in the Low-Temperature Thermal Properties of a Minimally
      Disordered Crystalline Solid.
AB  - The low-temperature thermal and transport properties of an unusual kind of
      crystal exhibiting minimal molecular positional and tilting disorder have been
      measured. The material, namely, low-dimensional, highly anisotropic
      pentachloronitrobenzene has a layered structure of rhombohedral parallel planes
      in which the molecules execute large-amplitude in-plane as well as concurrent out
      of-plane librational motions. Our study reveals that low-temperature glassy
      anomalies can be found in a system with minimal disorder due to the freezing of
      (mostly in-plane) reorientational jumps of molecules between equivalent
      crystallographic positions with partial site occupation. Our findings will pave
      the way to a deeper understanding of the origin of the above-mentioned universal
      glassy properties at low temperature.

PMID- 29219417
TI  - Nonlinear Focusing in Dynamic Crack Fronts and the Microbranching Transition.
AB  - Cracks in brittle materials produce two types of generic surface structures:
      facets at low velocities and microbranches at higher ones. Here we observe a
      transition from faceting to microbranching in polyacrylamide gels that is
      characterized by nonlinear dynamic localization of crack fronts. To better
      understand this process we derive a first-principles nonlinear equation of motion
      for crack fronts in the context of scalar elasticity. Its solution shows that
      nonlinear focusing coupled to rate dependence of dissipation governs the
      transition to microbranching.

PMID- 29219418
TI  - Correlated Three-Dimensional Imaging of Dislocations: Insights into the Onset of
      Thermal Slip in Semiconductor Wafers.
AB  - Correlated x-ray diffraction imaging and light microscopy provide a conclusive
      picture of three-dimensional dislocation arrangements on the micrometer scale.
      The characterization includes bulk crystallographic properties like Burgers
      vectors and determines links to structural features at the surface. Based on this
      approach, we study here the thermally induced slip-band formation at prior
      mechanical damage in Si wafers. Mobilization and multiplication of preexisting
      dislocations are identified as dominating mechanisms, and undisturbed long-range
      emission from regenerative sources is discovered.

PMID- 29219419
TI  - Enhanced Strength Through Nanotwinning in the Thermoelectric Semiconductor InSb.
AB  - The conversion efficiency (zT) of thermoelectric (TE) materials has been enhanced
      over the last two decades, but their engineering applications are hindered by the
      poor mechanical properties, especially the low strength at working conditions.
      Here we used density functional theory (DFT) to show a strength enhancement in
      the TE semiconductor InSb arising from the twin boundaries (TBs). This
      strengthening effect leads to an 11% enhancement of the ideal shear strength in
      flawless crystalline InSb where this theoretical strength is considered as an
      upper bound on the attainable strength for a realistic material. DFT calculations
      reveal that the directional covalent bond rearrangements at the TB accommodating
      the structural mismatch lead to the anisotropic resistance against the
      deformation combined with the enhanced TB rigidity. This produces a strong stress
      response in the nanotwinned InSb. This work provides a fundamental insight for
      understanding the deformation mechanism of nanotwinned TE semiconductors, which
      is beneficial for developing reliable TE devices.

PMID- 29219420
TI  - SiO_{2} Glass Density to Lower-Mantle Pressures.
AB  - The convection or settling of matter in the deep Earth's interior is mostly
      constrained by density variations between the different reservoirs. Knowledge of
      the density contrast between solid and molten silicates is thus of prime
      importance to understand and model the dynamic behavior of the past and present
      Earth. SiO_{2} is the main constituent of Earth's mantle and is the reference
      model system for the behavior of silicate melts at high pressure. Here, we apply
      our recently developed x-ray absorption technique to the density of SiO_{2} glass
      up to 110 GPa, doubling the pressure range for such measurements. Our density
      data validate recent molecular dynamics simulations and are in good agreement
      with previous experimental studies conducted at lower pressure. Silica glass
      rapidly densifies up to 40 GPa, but the density trend then flattens to become
      asymptotic to the density of SiO_{2} minerals above 60 GPa. The density data
      present two discontinuities at ~17 and ~60  GPa that can be related to a silicon
      coordination increase from 4 to a mixed 5/6 coordination and from 5/6 to sixfold,
      respectively. SiO_{2} glass becomes denser than MgSiO_{3} glass at ~40  GPa, and
      its density becomes identical to that of MgSiO_{3} glass above 80 GPa. Our
      results on SiO_{2} glass may suggest that a variation of SiO_{2} content in a
      basaltic or pyrolitic melt with pressure has at most a minor effect on the final
      melt density, and iron partitioning between the melts and residual solids is the
      predominant factor that controls melt buoyancy in the lowermost mantle.

PMID- 29219421
TI  - Correlation between Local Structure Order and Spatial Heterogeneity in a Metallic
      Glass.
AB  - Although nanoscale spatial heterogeneity of metallic glasses has been
      demonstrated by extensive experimental and theoretical investigations, the nature
      of spatial heterogeneity remains poorly known owing to the absence of a
      structural depiction of the inhomogeneity from experimental insight. Here we
      report the experimental characterization of the spatial heterogeneity of a
      metallic glass by utilizing state-of-the-art angstrom-beam electron diffraction
      and scanning transmission electron microscopy. The subnanoscale electron
      diffraction reveals that the nanoscale spatial heterogeneity and corresponding
      density fluctuation have a close correlation with the local structure variation
      from icosahedronlike to tetragonal crystal-like order. The structural insights of
      spatial heterogeneity have important implications in understanding the properties
      and dynamics of metallic glasses.

PMID- 29219422
TI  - Critical Role of the Exchange Interaction for the Electronic Structure and Charge
      Density-Wave Formation in TiSe_{2}.
AB  - We show that the inclusion of screened exchange via hybrid functionals provides a
      unified description of the electronic and vibrational properties of TiSe_{2}. In
      contrast to local approximations in density functional theory, the explicit
      inclusion of exact, nonlocal exchange captures the effects of the electron
      electron interaction needed to both separate the Ti-d states from the Se-p states
      and stabilize the charge-density-wave (CDW) (or low-T) phase through the
      formation of a p-d hybridized state. We further show that this leads to an
      enhanced electron-phonon coupling that can drive the transition even if a small
      gap opens in the high-T phase. Finally, we demonstrate that the hybrid
      functionals can generate a CDW phase where the electronic bands, the geometry,
      and the phonon frequencies are in agreement with experiments.

PMID- 29219423
TI  - Pure Even Harmonic Generation from Oriented CO in Linearly Polarized Laser
      Fields.
AB  - The first high harmonic spectrum containing only the odd orders was observed in
      experiments 30 years ago. However, a spectrum containing pure even harmonics has
      never been observed. We investigate the generation of pure even harmonics from
      oriented CO molecules in linearly polarized laser fields employing the time
      dependent density-functional theory. We find that the even harmonics, with no odd
      orders, are generated with the polarization perpendicular to the laser
      polarization when the molecular axis of CO is perpendicular to the laser
      polarization. The generation of pure even harmonics reveals a type of dipole
      acceleration originating from the permanent dipole moment. This phenomenon exists
      in all systems with permanent dipole moments, including bulk crystal and
      polyatomic molecules.

PMID- 29219424
TI  - Two-Particle Four-Mode Interferometer for Atoms.
AB  - We present a free-space interferometer to observe two-particle interference of a
      pair of atoms with entangled momenta. The source of atom pairs is a Bose-Einstein
      condensate subject to a dynamical instability, and the interferometer is realized
      using Bragg diffraction on optical lattices, in the spirit of our recent Hong-Ou
      Mandel experiment. We report on an observation ruling out the possibility of a
      purely mixed state at the input of the interferometer. We explain how our current
      setup can be extended to enable a test of a Bell inequality on momentum
      observables.

PMID- 29219425
TI  - Universal Coherence-Induced Power Losses of Quantum Heat Engines in Linear
      Response.
AB  - We identify a universal indicator for the impact of coherence on periodically
      driven quantum devices by dividing their power output into a classical
      contribution and one stemming solely from superpositions. Specializing to
      Lindblad dynamics and small driving amplitudes, we derive general upper bounds on
      both the coherent and the total power of cyclic heat engines. These constraints
      imply that, for sufficiently slow driving, coherence inevitably leads to power
      losses in the linear-response regime. We illustrate our theory by working out the
      experimentally relevant example of a single-qubit engine.

PMID- 29219426
TI  - Interatomic Spin Coupling in Manganese Clusters Registered on Graphene.
AB  - Different interatomic spin interactions in graphene-regulated Mn atomic clusters
      are investigated by low-temperature scanning tunneling microscopy and magnetic
      field-dependent inelastic spin excitation spectroscopy. All dimers observed
      exhibit an antiferromagnetic (AFM) singlet ground state and spin transition from
      the singlet to triplet states, but their AFM coupling strength shows a unique
      dependence on their site registration on the graphene. Intriguing spin coupling
      can be found in the graphene-mediated Mn trimers, which manifest multilevel spin
      excitations. In combination with Heisenberg spin modeling and first-principles
      numerical simulation, an exclusive noncollinear spin configuration of the Mn
      trimer regulated by the graphene template can be determined, and our observed
      experimental exchange energies cannot be understood by a direct spin exchange
      mechanism, but suggest a nonlocal Ruderman-Kittel-Kasuya-Yosida indirect spin
      exchange mechanism through substrate modulation, which has not yet been achieved
      in graphene so far.

PMID- 29219427
TI  - No Smooth Beginning for Spacetime.
AB  - We identify a fundamental obstruction to any theory of the beginning of the
      Universe, formulated as a semiclassical path integral. The Hartle-Hawking no
      boundary proposal and Vilenkin's tunneling proposal are examples of such
      theories. Each may be formulated as the quantum amplitude for obtaining a final 3
      geometry by integrating over 4-geometries. We introduce a new mathematical tool
      Picard-Lefschetz theory-for defining the semiclassical path integral for gravity.
      The Lorentzian path integral for quantum cosmology with a positive cosmological
      constant is mathematically meaningful in this approach, but the Euclidean version
      is not. The Lorentzian-Picard-Lefschetz formulation yields unambiguous
      predictions. Unfortunately, the outcome is that primordial tensor (gravitational
      wave) fluctuations are unsuppressed. We prove a general theorem to this effect,
      in a wide class of theories.

PMID- 29219428
TI  - Chiral Anomaly as the Origin of the Planar Hall Effect in Weyl Semimetals.
AB  - In condensed matter physics, the term "chiral anomaly" implies the violation of
      the separate number conservation laws of Weyl fermions of different chiralities
      in the presence of parallel electric and magnetic fields. One effect of the
      chiral anomaly in the recently discovered Dirac and Weyl semimetals is a positive
      longitudinal magnetoconductance. Here we show that chiral anomaly and nontrivial
      Berry curvature effects engender another striking effect in Weyl semimetals, the
      planar Hall effect (PHE). Remarkably, the PHE manifests itself when the applied
      current, magnetic field, and the induced transverse "Hall" voltage all lie in the
      same plane, precisely in a configuration in which the conventional Hall effect
      vanishes. In this work we treat the PHE quasiclassically, and predict specific
      experimental signatures for type-I and type-II Weyl semimetals that can be
      directly checked in experiments.

PMID- 29219429
TI  - Superanomalous Skin Effect for Surface Plasmon Polaritons.
AB  - It is commonly assumed that surface plasmon-polariton (SPP) excitations on a
      metal-dielectric interface decay exponentially inside the metallic sample. Here,
      we show that in a wide spectral interval the SPP field decays much slower, being
      inversely proportional to the distance to the interface modified by an additional
      logarithmic factor. This dependence differs from the standard anomalous skin
      effect and is provisionally referred to as superanomalous. Its origin is the
      nonlocality and the logarithmic singularity of the dielectric permittivity in
      metals. This type of decay is pronounced for SPP modes of higher frequencies, but
      it is suppressed for light waves.

PMID- 29219430
TI  - Gravitational Waves from Binary Black Hole Mergers inside Stars.
AB  - We present results from a controlled numerical experiment investigating the
      effect of stellar density gas on the coalescence of binary black holes (BBHs) and
      the resulting gravitational waves (GWs). This investigation is motivated by the
      proposed stellar core fragmentation scenario for BBH formation and the associated
      possibility of an electromagnetic counterpart to a BBH GW event. We employ full
      numerical relativity coupled with general-relativistic hydrodynamics and set up a
      30+30  M_{?} BBH (motivated by GW150914) inside gas with realistic stellar
      densities. Our results show that at densities rho?10^{6}-10^{7}  g cm^{-3}
      dynamical friction between the BHs and gas changes the coalescence dynamics and
      the GW signal in an unmistakable way. We show that for GW150914, LIGO
      observations appear to rule out BBH coalescence inside stellar gas of rho?10^{7} 
      g cm^{-3}. Typical densities in the collapsing cores of massive stars are in
      excess of this density. This excludes the fragmentation scenario for the
      formation of GW150914.

PMID- 29219431
TI  - Axicon Lens for Electrons Using a Magnetic Vortex: The Efficient Generation of a
      Bessel Beam.
AB  - We demonstrate experimentally an efficient electron axicon lens using a magnetic
      vortex. We show that naturally occurring magnetic vortices with circular magnetic
      moment distributions in a soft-magnetic thin film create conical phase shifts for
      fast electrons. Such radially symmetric linear phase ramps are equivalent to
      ideal light optical axicons. We apply this lens to generate efficient
      nondiffracting electron Bessel beams, which we observe experimentally in through
      focus Lorentz images as well as in propagated off-axis electron holograms. This
      highlights the potential for using magnetic nanostructures as highly efficient
      and flexible phase plates for crafting desired electron beam shapes.

PMID- 29219432
TI  - Anisotropy and Suppression of Spin-Orbit Interaction in a GaAs Double Quantum
      Dot.
AB  - The spin-flip tunneling rates are measured in GaAs-based double quantum dots by
      time-resolved charge detection. Such processes occur in the Pauli spin blockade
      regime with two electrons occupying the double quantum dot. Ways are presented
      for tuning the spin-flip tunneling rate, which on the one hand gives access to
      measuring the Rashba and Dresselhaus spin-orbit coefficients. On the other hand,
      they make it possible to turn on and off the effect of spin-orbit interaction
      with a high on/off ratio. The tuning is accomplished by choosing the alignment of
      the tunneling direction with respect to the crystallographic axes, as well as by
      choosing the orientation of the external magnetic field with respect to the spin
      orbit magnetic field. Spin lifetimes of 10 s are achieved at a tunneling rate
      close to 1 kHz.

PMID- 29219433
TI  - Vortices Enhance Diffusion in Dense Granular Flows.
AB  - This Letter introduces unexpected diffusion properties in dense granular flows
      and shows that they result from the development of partially jammed clusters of
      grains, or granular vortices. Transverse diffusion coefficients D and average
      vortex sizes l are systematically measured in simulated plane shear flows at
      differing inertial numbers I revealing (i) a strong deviation from the expected
      scaling D?d^{2}gamma[over ] involving the grain size d and shear rate gamma[over
      ] and (ii) an increase in average vortex size l at low I, following l?dI^{-1/2}
      but limited by the system size. A general scaling D?ldgamma[over ] is introduced
      that captures all the measurements and highlights the key role of vortex size.
      This leads to establishing a scaling for the diffusivity in dense granular flow
      as D?d^{2}sqrt[gamma[over ]/t_{i}] involving the geometric average of shear time
      1/gamma[over ] and inertial time t_{i} as the relevant time scale. Analysis of
      grain trajectories is further evidence that this diffusion process arises from a
      vortex-driven random walk.

PMID- 29219434
TI  - Separation of Isotopes in Space and Time by Gas-Surface Atomic Diffraction.
AB  - The separation of isotopes in space and time by gas-surface atomic diffraction is
      presented as a new means for isotopic enrichment. A supersonic beam of natural
      abundance neon is scattered from a periodic surface of methyl-terminated silicon,
      with the ^{20}Ne and ^{22}Ne isotopes scattering into unique diffraction
      channels. Under the experimental conditions presented in this Letter, a single
      pass yields an enrichment factor 3.50+/-0.30 for the less abundant isotope,
      ^{22}Ne, with extension to multiple passes easily envisioned. The velocity
      distribution of the incident beam is demonstrated to be the determining factor in
      the degree of separation between the isotopes' diffraction peaks. In cases where
      there is incomplete angular separation, the difference in arrival times of the
      two isotopes at a given scattered angle can be exploited to achieve complete
      temporal separation of the isotopes. This study explores the novel application of
      supersonic molecular beam studies as a viable candidate for separation of
      isotopes without the need for ionization or laser excitation.

PMID- 29219435
TI  - Chemical Enhancements in Shock-Accelerated Particles: Ab initio Simulations.
AB  - We study the thermalization, injection, and acceleration of ions with different
      mass/charge ratios, A/Z, in nonrelativistic collisionless shocks via hybrid
      (kinetic ions-fluid electrons) simulations. In general, ions thermalize to a
      postshock temperature proportional to A. When diffusive shock acceleration is
      efficient, ions develop a nonthermal tail whose extent scales with Z and whose
      normalization is enhanced as (A/Z)^{2} so that incompletely ionized heavy ions
      are preferentially accelerated. We discuss how these findings can explain
      observed heavy-ion enhancements in Galactic cosmic rays.

PMID- 29219436
TI  - Nonadiabatic Vibrational Damping of Molecular Adsorbates: Insights into
      Electronic Friction and the Role of Electronic Coherence.
AB  - We present a perturbation approach rooted in time-dependent density-functional
      theory to calculate electron-hole (e-h) pair excitation spectra during the
      nonadiabatic vibrational damping of adsorbates on metal surfaces. Our analysis
      for the benchmark systems CO on Cu(100) and Pt(111) elucidates the surprisingly
      strong influence of rather short electronic coherence times. We demonstrate how
      in the limit of short electronic coherence times, as implicitly assumed in
      prevalent quantum nuclear theories for the vibrational lifetimes as well as
      electronic friction, band structure effects are washed out. Our results suggest
      that more accurate lifetime or chemicurrentlike experimental measurements could
      characterize the electronic coherence.

PMID- 29219437
TI  - Comment on "Divergent and Ultrahigh Thermal Conductivity in Millimeter-Long
      Nanotubes".

PMID- 29219438
TI  - Observation of the Borromean Three-Body Forster Resonances for Three Interacting
      Rb Rydberg Atoms.
AB  - Three-body Forster resonances at long-range interactions of Rydberg atoms were
      first predicted and observed in Cs Rydberg atoms by Faoro et al. [Nat. Commun. 6,
      8173 (2015)NCAOBW2041-172310.1038/ncomms9173]. In these resonances, one of the
      atoms carries away an energy excess preventing the two-body resonance, leading
      thus to a Borromean type of Forster energy transfer. But they were in fact
      observed as the average signal for the large number of atoms N?1. In this Letter,
      we report on the first experimental observation of the three-body Forster
      resonances 3*nP_{3/2}(|M|)->nS_{1/2}+(n+1)S_{1/2}+nP_{3/2}(|M^{*}|) in a few Rb
      Rydberg atoms with n=36, 37. We have found here clear evidence that there is no
      signature of the three-body Forster resonance for exactly two interacting Rydberg
      atoms, while it is present for N=3-5 atoms. This demonstrates the assumption that
      three-body resonances can generalize to any Rydberg atom. As such resonance
      represents an effective three-body operator, it can be used to directly control
      the three-body interactions in quantum simulations and quantum information
      processing with Rydberg atoms.

PMID- 29219439
TI  - Strongly Asymmetric Spectroscopy in Plasmon-Exciton Hybrid Systems due to
      Interference-Induced Energy Repartitioning.
AB  - Recent intense effort has been devoted to exploring different manifestations of
      resonant excitations of strongly coupled plasmons and excitons, but so far such
      studies have been limited to situations where the Fano- or Rabi-type spectra are
      largely symmetric at zero detuning. Using a newly developed full quantum
      mechanical model, here we reveal the existence of a highly asymmetric
      spectroscopic regime for both the Rabi splitting and transparency dip. The
      asymmetric nature is inherently tied to the non-negligible exciton absorbance and
      is caused by substantial interference-induced energy repartitioning of the
      resonance peaks. This theoretical framework can be exploited to reveal the
      quantum behaviors of the two excitation entities with varying mutual coupling
      strengths in both linear and nonlinear regimes. We also use prototypical systems
      of rhodamine molecules strongly coupled with AuAg alloyed nanoparticles and well
      devised control experiments to demonstrate the validity and tunability of the
      energy repartitioning and correlated electronic state occupations, as captured by
      the variations in the asymmetric spectroscopy and corresponding nonlinear
      absorption coefficient as a function of the Au:Ag ratio. The present study helps
      to substantially enrich our microscopic understanding of strongly coupled plasmon
      exciton systems.

PMID- 29219440
TI  - No Thermalization without Correlations.
AB  - The proof of the long-standing conjecture is presented that Markovian quantum
      master equations are at odds with quantum thermodynamics under conventional
      assumptions of fluctuation-dissipation theorems (implying a translation invariant
      dissipation). Specifically, except for identified systems, persistent system-bath
      correlations of at least one kind, spatial or temporal, are obligatory for
      thermalization. A systematic procedure is proposed to construct translation
      invariant bath models producing steady states that well approximate thermal
      states. A quantum optical scheme for the laboratory assessment of the developed
      procedure is outlined.

PMID- 29219441
TI  - Phase Coexistence in Insect Swarms.
AB  - Animal aggregations are visually striking, and as such are popular examples of
      collective behavior in the natural world. Quantitatively demonstrating the
      collective nature of such groups, however, remains surprisingly difficult.
      Inspired by thermodynamics, we applied topological data analysis to laboratory
      insect swarms and found evidence for emergent, material-like states. We show that
      the swarms consist of a core "condensed" phase surrounded by a dilute "vapor"
      phase. These two phases coexist in equilibrium, and maintain their distinct
      macroscopic properties even though individual insects pass freely between them.
      We further define a pressure and chemical potential to describe these phases,
      extending theories of active matter to aggregations of macroscopic animals and
      laying the groundwork for a thermodynamic description of collective animal
      groups.

PMID- 29219442
TI  - Electrokinetic Control of Viscous Fingering.
AB  - We present a theory of the interfacial stability of two immiscible electrolytes
      under the coupled action of pressure gradients and electric fields in a Hele-Shaw
      cell or porous medium. Mathematically, our theory describes a phenomenon of
      "vector Laplacian growth," in which the interface moves in response to the
      gradient of a vector-valued potential function through a generalized mobility
      tensor. Physically, we extend the classical Saffman-Taylor problem to
      electrolytes by incorporating electrokinetic (EK) phenomena. A surprising
      prediction is that viscous fingering can be controlled by varying the injection
      ratio of electric current to flow rate. Beyond a critical injection ratio,
      stability depends only upon the relative direction of flow and current,
      regardless of the viscosity ratio. Possible applications include porous materials
      processing, electrically enhanced oil recovery, and EK remediation of
      contaminated soils.

PMID- 29219443
TI  - Fundamental Bounds on First Passage Time Fluctuations for Currents.
AB  - Current is a characteristic feature of nonequilibrium systems. In stochastic
      systems, these currents exhibit fluctuations constrained by the rate of
      dissipation in accordance with the recently discovered thermodynamic uncertainty
      relation. Here, we derive a conjugate uncertainty relationship for the first
      passage time to accumulate a fixed net current. More generally, we use the tools
      of large-deviation theory to simply connect current fluctuations and first
      passage time fluctuations in the limit of long times and large currents. With
      this connection, previously discovered symmetries and bounds on the large
      deviation function for currents are readily transferred to first passage times.

PMID- 29219444
TI  - Dynamic Scaling of Colloidal Gel Formation at Intermediate Concentrations.
AB  - We have examined the formation and dissolution of gels composed of intermediate
      volume-fraction nanoparticles with temperature-dependent short-range attractions
      using small-angle x-ray scattering, x-ray photon correlation spectroscopy, and
      rheology to obtain nanoscale and macroscale sensitivity to structure and
      dynamics. Gel formation after temperature quenches to the vicinity of the
      rheologically determined gel temperature, T_{gel}, was characterized via the
      slowdown of dynamics and changes in microstructure observed in the intensity
      autocorrelation functions and structure factor, respectively, as a function of
      quench depth (DeltaT=T_{quench}-T_{gel}), wave vector, and formation time t_{f}.
      We find the wave-vector-dependent dynamics, microstructure, and rheology at a
      particular DeltaT and t_{f} map to those at other DeltaTs and t_{f}s via an
      effective scaling temperature, T_{s}. A single T_{s} applies to a broad range of
      DeltaT and t_{f} but does depend on the particle size. The rate of formation
      implied by the scaling is a far stronger function of DeltaT than expected from
      the attraction strength between colloids. We interpret this strong temperature
      dependence in terms of cooperative bonding required to form stable gels via
      energetically favored, local structures.

PMID- 29219445
TI  - Fast Quantum State Transfer and Entanglement Renormalization Using Long-Range
      Interactions.
AB  - In short-range interacting systems, the speed at which entanglement can be
      established between two separated points is limited by a constant Lieb-Robinson
      velocity. Long-range interacting systems are capable of faster entanglement
      generation, but the degree of the speedup possible is an open question. In this
      Letter, we present a protocol capable of transferring a quantum state across a
      distance L in d dimensions using long-range interactions with a strength bounded
      by 1/r^{alpha}. If alpha<d, the state transfer time is asymptotically independent
      of L; if alpha=d, the time scales logarithmically with the distance L; if
      d<alpha<d+1, the transfer occurs in a time proportional to L^{alpha-d}; and if
      alpha>=d+1, it occurs in a time proportional to L. We then use this protocol to
      upper bound the time required to create a state specified by a multiscale
      entanglement renormalization ansatz (MERA) tensor network and show that if the
      linear size of the MERA state is L, then it can be created in a time that scales
      with L identically to the state transfer up to logarithmic corrections. This
      protocol realizes an exponential speedup in cases of alpha=d, which could be
      useful in creating large entangled states for dipole-dipole (1/r^{3})
      interactions in three dimensions.

PMID- 29219446
TI  - Control of Chiral Magnetism Through Electric Fields in Multiferroic Compounds
      above the Long-Range Multiferroic Transition.
AB  - Polarized neutron scattering experiments reveal that type-II multiferroics allow
      for controlling the spin chirality by external electric fields even in the
      absence of long-range multiferroic order. In the two prototype compounds
      TbMnO_{3} and MnWO_{4}, chiral magnetism associated with soft overdamped
      electromagnons can be observed above the long-range multiferroic transition
      temperature T_{MF}, and it is possible to control it through an electric field.
      While MnWO_{4} exhibits chiral correlations only in a tiny temperature interval
      above T_{MF}, in TbMnO_{3} chiral magnetism can be observed over several kelvin
      up to the lock-in transition, which is well separated from T_{MF}.

PMID- 29219448
TI  - Improving the Functional Control of Aged Ferroelectrics Using Insights from
      Atomistic Modeling.
AB  - We provide a fundamental insight into the microscopic mechanisms of the aging
      processes. Using large-scale molecular dynamics simulations of the prototypical
      ferroelectric material PbTiO_{3}, we demonstrate that the experimentally observed
      aging phenomena can be reproduced from intrinsic interactions of defect dipoles
      related to dopant-vacancy associates, even in the absence of extrinsic effects.
      We show that variation of the dopant concentration modifies the material's
      hysteretic response. We identify a universal method to reduce loss and tune the
      electromechanical properties of inexpensive ceramics for efficient technologies.

PMID- 29219449
TI  - Analytic Solutions to Coherent Control of the Dirac Equation.
AB  - A simple framework for Dirac spinors is developed that parametrizes admissible
      quantum dynamics and also analytically constructs electromagnetic fields, obeying
      Maxwell's equations, which yield a desired evolution. In particular, we show how
      to achieve dispersionless rotation and translation of wave packets. Additionally,
      this formalism can handle control interactions beyond electromagnetic. This work
      reveals unexpected flexibility of the Dirac equation for control applications,
      which may open new prospects for quantum technologies.

PMID- 29219450
TI  - Dimensional Crossover-Induced Topological Hall Effect in a Magnetic Topological
      Insulator.
AB  - We report transport studies of Mn-doped Bi_{2}Te_{3} topological insulator (TI)
      films with an accurately controlled thickness grown by molecular beam epitaxy. We
      find that films thicker than five quintuple layers (QLs) exhibit the usual
      anomalous Hall effect for magnetic TIs. When the thickness is reduced to four
      QLs, however, characteristic features associated with the topological Hall effect
      (THE) emerge. More surprisingly, the THE vanishes again when the film thickness
      is further reduced to three QLs. Theoretical calculations demonstrate that the
      coupling between the top and bottom surface states at the dimensional crossover
      regime stabilizes the magnetic Skyrmion structure that is responsible for the
      THE.

PMID- 29219451
TI  - Joint Space-Time Coherent Vibration Driven Conformational Transitions in a Single
      Molecule.
AB  - We report single-molecule conformational transitions with joint angstrom
      femtosecond resolution by irradiating the junction of a scanning tunneling
      microscope with femtosecond laser pulses. An isolated pyrrolidine molecule
      adsorbed on a Cu(001) surface undergoes reversible transitions between two
      conformational states. The transition rate decays in time and exhibits sinusoidal
      oscillations with periods of specific molecular vibrations. The dynamics of this
      transition depends sensitively on the molecular environment, as exemplified by
      the effects of another molecule in proximity.

PMID- 29219452
TI  - Measurement of Body-Centered-Cubic Aluminum at 475 GPa.
AB  - Nanosecond in situ x-ray diffraction and simultaneous velocimetry measurements
      were used to determine the crystal structure and pressure, respectively, of ramp
      compressed aluminum at stress states between 111 and 475 GPa. The solid-solid Al
      phase transformations, fcc-hcp and hcp-bcc, are observed at 216+/-9 and 321+/-12 
      GPa, respectively, with the bcc phase persisting to 475 GPa. The high-pressure
      crystallographic texture of the hcp and bcc phases suggests close-packed or
      nearly close-packed lattice planes remain parallel through both transformations.

PMID- 29219453
TI  - Bell Correlations in a Many-Body System with Finite Statistics.
AB  - A recent experiment reported the first violation of a Bell correlation witness in
      a many-body system [Science 352, 441 (2016)]. Following discussions in this
      Letter, we address here the question of the statistics required to witness Bell
      correlated states, i.e., states violating a Bell inequality, in such experiments.
      We start by deriving multipartite Bell inequalities involving an arbitrary number
      of measurement settings, two outcomes per party and one- and two-body correlators
      only. Based on these inequalities, we then build up improved witnesses able to
      detect Bell correlated states in many-body systems using two collective
      measurements only. These witnesses can potentially detect Bell correlations in
      states with an arbitrarily low amount of spin squeezing. We then establish an
      upper bound on the statistics needed to convincingly conclude that a measured
      state is Bell correlated.

PMID- 29219454
TI  - Publisher's Note: Kinetic Simulations of the Interruption of Large-Amplitude
      Shear-Alfven Waves in a High-beta Plasma [Phys. Rev. Lett. 119, 155101 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.155101.

PMID- 29219455
TI  - Universal Quantum Computation with Gapped Boundaries.
AB  - This Letter discusses topological quantum computation with gapped boundaries of
      two-dimensional topological phases. Systematic methods are presented to encode
      quantum information topologically using gapped boundaries, and to perform
      topologically protected operations on this encoding. In particular, we introduce
      a new and general computational primitive of topological charge measurement and
      present a symmetry-protected implementation of this primitive. Throughout the
      Letter, a concrete physical example, the Z_{3} toric code [D(Z_{3})], is
      discussed. For this example, we have a qutrit encoding and an abstract universal
      gate set. Physically, gapped boundaries of D(Z_{3}) can be realized in bilayer
      fractional quantum Hall 1/3 systems. If a practical implementation is found for
      the required topological charge measurement, these boundaries will give rise to a
      direct physical realization of a universal quantum computer based on a purely
      Abelian topological phase.

PMID- 29219456
TI  - Melting Can Hinder Impact-Induced Adhesion.
AB  - Melting has long been used to join metallic materials, from welding to selective
      laser melting in additive manufacturing. In the same school of thought, localized
      melting has been generally perceived as an advantage, if not the main mechanism,
      for the adhesion of metallic microparticles to substrates during a supersonic
      impact. Here, we conduct the first in situ supersonic impact observations of
      individual metallic microparticles aimed at the explicit study of melting
      effects. Counterintuitively, we find that under at least some conditions melting
      is disadvantageous and hinders impact-induced adhesion. In the parameter space
      explored, i.e., ~10  MUm particle size and ~1  km/s particle velocity, we argue
      that the solidification time is much longer than the residence time of the
      particle on the substrate, so that resolidification cannot be a significant
      factor in adhesion.

PMID- 29219457
TI  - Finite Temperature Green's Function Approach for Excited State and Thermodynamic
      Properties of Cool to Warm Dense Matter.
AB  - We present a finite-temperature extension of the retarded cumulant Green's
      function for calculations of exited-state, correlation, and thermodynamic
      properties of electronic systems. The method incorporates a cumulant to leading
      order in the screened Coulomb interaction W, and improves on the GW approximation
      of many-body perturbation theory. Results for the homogeneous electron gas are
      presented for a wide range of densities and temperatures, from cool to warm dense
      matter regimes, which reveal several hitherto unexpected properties. For example,
      correlation effects remain strong at high T while the exchange-correlation energy
      becomes small; also the spectral function broadens and damping increases with
      temperature, blurring the usual quasiparticle picture. These effects are evident,
      e.g., in Compton scattering which exhibits many-body corrections that persist at
      normal densities and intermediate T. The approach also yields exchange
      correlation energies and potentials in good agreement with existing methods.

PMID- 29219447
TI  - Search for CP Violation and Measurement of the Branching Fraction in the Decay
      D^{0}->K_{S}^{0}K_{S}^{0}.
AB  - We report a study of the decay D^{0}->K_{S}^{0}K_{S}^{0} using 921  fb^{-1} of
      data collected at or near the Upsilon(4S) and Upsilon(5S) resonances with the
      Belle detector at the KEKB asymmetric energy e^{+}e^{-} collider. The measured
      time-integrated CP asymmetry is A_{CP}(D^{0}->K_{S}^{0}K_{S}^{0})=(-0.02+/-1.53+/
      0.02+/-0.17)%, and the branching fraction is B(D^{0}
      >K_{S}^{0}K_{S}^{0})=(1.321+/-0.023+/-0.036+/-0.044)*10^{-4}, where the first
      uncertainty is statistical, the second is systematic, and the third is due to the
      normalization mode (D^{0}->K_{S}^{0}pi^{0}). These results are significantly more
      precise than previous measurements available for this mode. The A_{CP}
      measurement is consistent with the standard model expectation.

PMID- 29219458
TI  - Detection of Microwave Transitions between Ortho and Para States in a Free
      Isolated Molecule.
AB  - Microwave transitions between the ortho and para states of the S_{2}Cl_{2}
      molecule in a free isolated condition are observed for the first time. In the
      theoretical treatment, we derive eigenfunctions of an effective Hamiltonian
      including the ortho-para interaction to calculate the intensities and frequencies
      of forbidden ortho-para transitions in the cm-wave region and pick up some
      promising candidates for the spectroscopic detection. In the experiment,
      transitions of the S_{2}Cl_{2} molecule under a supersonic jet condition are
      observed with a Fourier transform microwave spectrometer. Seven hyperfine
      resolved rotational transitions including the lowest rotational level are
      detected as the ortho-para transitions at the predicted frequencies within the
      experimental errors. The observed intensities are about 10^{-3} times the allowed
      transitions, which are consistent with the predictions based on the intensity
      borrowing model. This result suggests that the ortho-para conversion of this
      molecule occurs in a few thousand years through spontaneous emission even in a
      circumstance where molecular collisions occur rarely like in interstellar space.

PMID- 29219459
TI  - Electronic-Structure Origin of Cation Disorder in Transition-Metal Oxides.
AB  - Cation disorder is an important design criterion for technologically relevant
      transition-metal (TM) oxides, such as radiation-tolerant ceramics and Li-ion
      battery electrodes. In this Letter, we use a combination of first-principles
      calculations, normal mode analysis, and band-structure arguments to pinpoint a
      specific electronic-structure effect that influences the stability of disordered
      phases. We find that the electronic configuration of a TM ion determines to what
      extent the structural energy is affected by site distortions. This mechanism
      explains the stability of disordered phases with large ionic radius differences
      and provides a concrete guideline for the discovery of novel disordered
      compositions.

PMID- 29219460
TI  - Oxidation-Mediated Fingering in Liquid Metals.
AB  - We identify and characterize a new class of fingering instabilities in liquid
      metals; these instabilities are unexpected due to the large interfacial tension
      of metals. Electrochemical oxidation lowers the effective interfacial tension of
      a gallium-based liquid metal alloy to values approaching zero, thereby inducing
      drastic shape changes, including the formation of fractals. The measured fractal
      dimension (D=1.3+/-0.05) places the instability in a different universality class
      than other fingering instabilities. By characterizing changes in morphology and
      dynamics as a function of droplet volume and applied electric potential, we
      identify the three main forces involved in this process: interfacial tension,
      gravity, and oxidative stress. Importantly, we find that electrochemical
      oxidation can generate compressive interfacial forces that oppose the tensile
      forces at a liquid interface. The surface oxide layer ultimately provides a
      physical and electrochemical barrier that halts the instabilities at larger
      positive potentials. Controlling the competition between interfacial tension and
      oxidative (compressive) stresses at the interface is important for the
      development of reconfigurable electronic, electromagnetic, and optical devices
      that take advantage of the metallic properties of liquid metals.

PMID- 29219461
TI  - Origin of Spectral Band Patterns in the Cosmic Unidentified Infrared Emission.
AB  - The cosmic unidentified infrared emission (UIE) band phenomenon is generally
      considered as indicative of free-flying polycyclic aromatic hydrocarbon molecules
      in space. However, a coherent explanation of emission spectral band patterns
      depending on astrophysical source is yet to be resolved under this attribution.
      Meanwhile astronomers have restored the alternative origin as due to amorphous
      carbon particles, but assigning spectral patterns to specific structural elements
      of particles is equally challenging. Here we report a physical principle in which
      inclusion of nonplanar structural defects in aromatic core molecular structures
      (pi domains) induces spectral patterns typical of the phenomenon. We show that
      defects in model pi domains modulate the electronic-vibration coupling that
      activates the delocalized pi-electron contribution to aromatic vibrational modes.
      The modulation naturally disperses C=C stretch modes in band patterns that
      readily resemble the UIE bands in the elusive 6-9  MUm range. The electron
      vibration interaction mechanics governing the defect-induced band patterns
      underscores the importance of pi delocalization in the emergence of UIE bands. We
      discuss the global UIE band regularity of this range as compatible with an
      emission from the delocalized sp^{2} phase, as pi domains, confined in disordered
      carbon mixed-phase aggregates.

PMID- 29219462
TI  - Numerical Study of Quantum Hall Bilayers at Total Filling nu_{T}=1: A New Phase
      at Intermediate Layer Distances.
AB  - We study the phase diagram of quantum Hall bilayer systems with total filing
      nu_{T}=1/2+1/2 of the lowest Landau level as a function of layer distances d.
      Based on numerical exact diagonalization calculations, we obtain three distinct
      phases, including an exciton superfluid phase with spontaneous interlayer
      coherence at small d, a composite Fermi liquid at large d, and an intermediate
      phase for 1.1<d/l_{B}<1.8 (l_{B} is the magnetic length). The transition from the
      exciton superfluid to the intermediate phase is identified by (i) a dramatic
      change in the Berry curvature of the ground state under twisted boundary
      conditions on the two layers and (ii) an energy level crossing of the first
      excited state. The transition from the intermediate phase to the composite Fermi
      liquid is identified by the vanishing of the exciton superfluid stiffness.
      Furthermore, from our finite-size study, the energy cost of transferring one
      electron between the layers shows an even-odd effect and possibly extrapolates to
      a finite value in the thermodynamic limit, indicating the enhanced intralayer
      correlation. Our identification of an intermediate phase and its distinctive
      features shed new light on the theoretical understanding of the quantum Hall
      bilayer system at total filling nu_{T}=1.

PMID- 29219463
TI  - Gaussian Boson Sampling.
AB  - Boson sampling has emerged as a tool to explore the advantages of quantum over
      classical computers as it does not require universal control over the quantum
      system, which favors current photonic experimental platforms. Here, we introduce
      Gaussian Boson sampling, a classically hard-to-solve problem that uses squeezed
      states as a nonclassical resource. We relate the probability to measure specific
      photon patterns from a general Gaussian state in the Fock basis to a matrix
      function called the Hafnian, which answers the last remaining question of
      sampling from Gaussian states. Based on this result, we design Gaussian Boson
      sampling, a #P hard problem, using squeezed states. This demonstrates that Boson
      sampling from Gaussian states is possible, with significant advantages in the
      photon generation probability, compared to existing protocols.

PMID- 29219464
TI  - Separable and Inseparable Quantum Trajectories.
AB  - The dynamical behavior of interacting systems plays a fundamental role for
      determining quantum correlations, such as entanglement. In this Letter, we
      describe temporal quantum effects of the inseparable evolution of composite
      quantum states by comparing the trajectories to their classically correlated
      counterparts. For this reason, we introduce equations of motions describing the
      separable propagation of any interacting quantum system, which are derived by
      requiring separability for all times. The resulting Schrodinger-type equations
      allow for comparing the trajectories in a separable configuration with the actual
      behavior of the system and, thereby, identifying inseparable and time-dependent
      quantum properties. As an example, we study bipartite discrete- and continuous
      variable interacting systems. The generalization of our developed technique to
      multipartite scenarios is also provided.

PMID- 29219465
TI  - Emergent Bistability and Switching in a Nonequilibrium Crystal.
AB  - Multistability is an inseparable feature of many physical, chemical, and
      biological systems which are driven far from equilibrium. In these nonequilibrium
      systems, stochastic dynamics often induces switching between distinct states on
      emergent time scales; for example, bistable switching is a natural feature of
      noisy, spatially extended systems that consist of bistable elements.
      Nevertheless, here we present experimental evidence that bistable elements are
      not required for the global bistability of a system. We observe temporal
      switching between a crystalline, condensed state and a gaslike, excited state in
      a spatially extended, quasi-two-dimensional system of charged microparticles.
      Accompanying numerical simulations show that conservative forces, damping, and
      stochastic noise are sufficient to prevent steady-state equilibrium, leading to
      switching between the two states over a range of time scales, from seconds to
      hours.

PMID- 29219466
TI  - State-Independent Uncertainty Relations and Entanglement Detection in Noisy
      Systems.
AB  - Quantifying quantum mechanical uncertainty is vital for the increasing number of
      experiments that reach the uncertainty limited regime. We present a method for
      computing tight variance uncertainty relations, i.e., the optimal state
      independent lower bound for the sum of the variances for any set of two or more
      measurements. The bounds come with a guaranteed error estimate, so results of
      preassigned accuracy can be obtained straightforwardly. Our method also works for
      postive-operator-valued measurements. Therefore, it can be used for detecting
      entanglement in noisy environments, even in cases where conventional spin
      squeezing criteria fail because of detector noise.

PMID- 29219467
TI  - Interaction Heterogeneity can Favorably Impact Colloidal Crystal Nucleation.
AB  - Colloidal particles with short-ranged attractions, e.g., micron-scale spheres
      functionalized with single-stranded DNA oligomers, are susceptible to becoming
      trapped in disordered configurations even when a crystalline arrangement is the
      ground state. Moreover, for reasons that are not well understood, seemingly minor
      variations in the particle formulation can lead to dramatic changes in the
      crystallization outcome. We demonstrate, using a combination of equilibrium and
      nonequilibrium computer simulations, that interaction heterogeneity-variations in
      the energetic interactions among different particle pairs in the population-may
      favorably impact crystal nucleation. Specifically, interaction heterogeneity is
      found to lower the free energy barrier to nucleation via the formation of
      clusters comprised preferentially of strong-binding particle pairs. Moreover,
      gelation is inhibited by "spreading out over time" the nucleation process,
      resulting in a reduced density of stable nuclei, allowing each to grow unhindered
      and larger. Our results suggest a simple and robust approach for enhancing
      colloidal crystallization near the "sticky sphere" limit, and support the notion
      that differing extents of interaction heterogeneity arising from various particle
      functionalization protocols may contribute to the otherwise unexplained
      variations in crystallization outcomes reported in the literature.

PMID- 29219468
TI  - Disorder-Induced Dephasing in Backscattering-Free Quantum Transport.
AB  - We analyze the disorder-perturbed transport of quantum states in the absence of
      backscattering. This comprises, for instance, the propagation of edge-mode wave
      packets in topological insulators, or the propagation of photons in inhomogeneous
      media. We quantify the disorder-induced dephasing, which we show to be bound.
      Moreover, we identify a gap condition to remain in the backscattering-free regime
      despite disorder-induced momentum broadening. Our analysis comprises the full
      disorder-averaged quantum state, on the level of both populations and coherences,
      appreciating states as potential carriers of quantum information. The well
      definedness of states is guaranteed by our treatment of the nonequilibrium
      dynamics with Lindblad master equations.

PMID- 29219469
TI  - Possibility to Probe Negative Values of a Wigner Function in Scattering of a
      Coherent Superposition of Electronic Wave Packets by Atoms.
AB  - Within a plane-wave approximation in scattering, an incoming wave packet's Wigner
      function stays positive everywhere, which obscures such purely quantum phenomena
      as nonlocality and entanglement. With the advent of the electron microscopes with
      subnanometer-sized beams, one can enter a genuinely quantum regime where the
      latter effects become only moderately attenuated. Here we show how to probe
      negative values of the Wigner function in scattering of a coherent superposition
      of two Gaussian packets with a nonvanishing impact parameter between them (a
      Schrodinger's cat state) by atomic targets. For hydrogen in the ground 1s state,
      a small parameter of the problem, a ratio a/sigma_{?} of the Bohr radius a to the
      beam width sigma_{?}, is no longer vanishing. We predict an azimuthal asymmetry
      of the scattered electrons, which is found to be up to 10%, and argue that it can
      be reliably detected. The production of beams with the not-everywhere-positive
      Wigner functions and the probing of such quantum effects can open new
      perspectives for noninvasive electron microscopy, quantum tomography, particle
      physics, and so forth.

PMID- 29219470
TI  - Engineering an Insulating Ferroelectric Superlattice with a Tunable Band Gap from
      Metallic Components.
AB  - The recent discovery of "polar metals" with ferroelectriclike displacements
      offers the promise of designing ferroelectrics with tunable energy gaps by
      inducing controlled metal-insulator transitions. Here we employ first-principles
      calculations to design a metallic polar superlattice from nonpolar metal
      components and show that controlled intermixing can lead to a true insulating
      ferroelectric with a tunable band gap. We consider a 2/2 superlattice made of two
      centrosymmetric metallic oxides, La_{0.75}Sr_{0.25}MnO_{3} and LaNiO_{3}, and
      show that ferroelectriclike displacements are induced. The ferroelectriclike
      distortion is found to be strongly dependent on the carrier concentration (Sr
      content). Further, we show that a metal-to-insulator (MI) transition is feasible
      in this system via disproportionation of the Ni sites. Such a disproportionation
      and, hence, a MI transition can be driven by intermixing of transition metal ions
      between Mn and Ni layers. As a result, the energy gap of the resulting
      ferroelectric can be tuned by varying the degree of intermixing in the
      experimental fabrication method.

PMID- 29219471
TI  - High-Resolution Valley Spectroscopy of Si Quantum Dots.
AB  - We study an accumulation mode Si/SiGe double quantum dot (DQD) containing a
      single electron that is dipole coupled to microwave photons in a superconducting
      cavity. Measurements of the cavity transmission reveal dispersive features due to
      the DQD valley states in Si. The occupation of the valley states can be increased
      by raising the temperature or applying a finite source-drain bias across the DQD,
      resulting in an increased signal. Using the cavity input-output theory and a four
      level model of the DQD, it is possible to efficiently extract valley splittings
      and the inter- and intravalley tunnel couplings.

PMID- 29219472
TI  - Localized Control of Curie Temperature in Perovskite Oxide Film by Capping-Layer
      Induced Octahedral Distortion.
AB  - With reduced dimensionality, it is often easier to modify the properties of
      ultrathin films than their bulk counterparts. Strain engineering, usually
      achieved by choosing appropriate substrates, has been proven effective in
      controlling the properties of perovskite oxide films. An emerging alternative
      route for developing new multifunctional perovskite is by modification of the
      oxygen octahedral structure. Here we report the control of structural oxygen
      octahedral rotation in ultrathin perovskite SrRuO_{3} films by the deposition of
      a SrTiO_{3} capping layer, which can be lithographically patterned to achieve
      local control. Using a scanning Sagnac magnetic microscope, we show an increase
      in the Curie temperature of SrRuO_{3} due to the suppression octahedral rotations
      revealed by the synchrotron x-ray diffraction. This capping-layer-based technique
      may open new possibilities for developing functional oxide materials.

PMID- 29219474
TI  - Zero-Energy Modes from Coalescing Andreev States in a Two-Dimensional
      Semiconductor-Superconductor Hybrid Platform.
AB  - We investigate zero-bias conductance peaks that arise from coalescing subgap
      Andreev states, consistent with emerging Majorana zero modes, in hybrid
      semiconductor-superconductor wires defined in a two-dimensional InAs/Al
      heterostructure using top-down lithography and gating. The measurements indicate
      a hard superconducting gap, ballistic tunneling contact, and in-plane critical
      fields up to 3 T. Top-down lithography allows complex geometries, branched
      structures, and straightforward scaling to multicomponent devices compared to
      structures made from assembled nanowires.

PMID- 29219473
TI  - Two-Hierarchy Entanglement Swapping for a Linear Optical Quantum Repeater.
AB  - Quantum repeaters play a significant role in achieving long-distance quantum
      communication. In the past decades, tremendous effort has been devoted towards
      constructing a quantum repeater. As one of the crucial elements, entanglement has
      been created in different memory systems via entanglement swapping. The
      realization of j-hierarchy entanglement swapping, i.e., connecting quantum memory
      and further extending the communication distance, is important for implementing a
      practical quantum repeater. Here, we report the first demonstration of a fault
      tolerant two-hierarchy entanglement swapping with linear optics using parametric
      down-conversion sources. In the experiment, the dominant or most probable noise
      terms in the one-hierarchy entanglement swapping, which is on the same order of
      magnitude as the desired state and prevents further entanglement connections, are
      automatically washed out by a proper design of the detection setting, and the
      communication distance can be extended. Given suitable quantum memory, our
      techniques can be directly applied to implementing an atomic ensemble based
      quantum repeater, and are of significant importance in the scalable quantum
      information processing.

PMID- 29219475
TI  - Spin-Wave Chirality and Its Manifestations in Antiferromagnets.
AB  - As first demonstrated by Tang and Cohen in chiral optics, the asymmetry in the
      rate of electromagnetic energy absorption between left and right enantiomers is
      determined by an optical chirality density. Here, we demonstrate that this effect
      can exist in magnetic spin systems. By constructing a formal analogy with
      electrodynamics, we show that in antiferromagnets with broken chiral symmetry,
      the asymmetry in local spin-wave energy absorption is proportional to a spin-wave
      chirality density, which is a direct counterpart of optical zilch. We propose
      that injection of a pure spin current into an antiferromagnet may serve as a
      chiral symmetry breaking mechanism, since its effect in the spin-wave
      approximation can be expressed in terms of additional Lifshitz invariants. We use
      linear response theory to show that the spin current induces a nonequilibrium
      spin-wave chirality density.

PMID- 29219476
TI  - Giant Interatomic Energy-Transport Amplification with Nonreciprocal Photonic
      Topological Insulators.
AB  - We show that the energy-transport efficiency in a chain of two-level emitters can
      be drastically enhanced by the presence of a photonic topological insulator
      (PTI). This is obtained by exploiting the peculiar properties of its
      nonreciprocal surface plasmon polariton (SPP), which is unidirectional, and
      immune to backscattering, and propagates in the bulk band gap. This amplification
      of transport efficiency can be as much as 2 orders of magnitude with respect to
      reciprocal SPPs. Moreover, we demonstrate that despite the presence of
      considerable imperfections at the interface of the PTI, the efficiency of the SPP
      assisted energy transport is almost unaffected by discontinuities. We also show
      that the SPP properties allow energy transport over considerably much larger
      distances than in the reciprocal case, and we point out a particularly simple way
      to tune the transport. Finally, we analyze the specific case of a two-emitter
      chain and unveil the origin of the efficiency amplification. The efficiency
      amplification and the practical advantages highlighted in this work might be
      particularly useful in the development of new devices intended to manage energy
      at the atomic scale.

PMID- 29219477
TI  - Absence of Ergodicity without Quenched Disorder: From Quantum Disentangled
      Liquids to Many-Body Localization.
AB  - We study the time evolution after a quantum quench in a family of models whose
      degrees of freedom are fermions coupled to spins, where quenched disorder appears
      neither in the Hamiltonian parameters nor in the initial state. Focusing on the
      behavior of entanglement, both spatial and between subsystems, we show that the
      model supports a state exhibiting combined area and volume-law entanglement,
      being characteristic of the quantum disentangled liquid. This behavior appears
      for one set of variables, which is related via a duality mapping to another set,
      where this structure is absent. Upon adding density interactions between the
      fermions, we identify an exact mapping to an XXZ spin chain in a random binary
      magnetic field, thereby establishing the existence of many-body localization with
      its logarithmic entanglement growth in a fully disorder-free system.

PMID- 29219478
TI  - Loop Corrections to Supergravity on AdS_{5}*S^{5}.
AB  - We consider the four-point correlator of the stress-energy tensor multiplet in
      N=4 super Yang-Mills theory. In the planar limit and at large 't Hooft coupling,
      such a correlator is given by the corresponding holographic correlation function
      in IIB supergravity on AdS_{5}*S^{5}. We consider subleading corrections in the
      number of colors, i.e., order 1/N^{4}, at large 't Hooft coupling. This
      corresponds to loop corrections to the supergravity result. Consistency
      conditions, most notably, crossing symmetry, constrain the form of such
      corrections and lead to a complete determination of the spectrum of leading-twist
      intermediate operators.

PMID- 29219479
TI  - Spin-Tensor-Momentum-Coupled Bose-Einstein Condensates.
AB  - The recent experimental realization of spin-orbit coupling for ultracold atomic
      gases provides a powerful platform for exploring many interesting quantum
      phenomena. In these studies, spin represents the spin vector (spin 1/2 or spin 1)
      and orbit represents the linear momentum. Here we propose a scheme to realize a
      new type of spin-tensor-momentum coupling (STMC) in spin-1 ultracold atomic
      gases. We study the ground state properties of interacting Bose-Einstein
      condensates with STMC and find interesting new types of stripe superfluid phases
      and multicritical points for phase transitions. Furthermore, STMC makes it
      possible to study quantum states with dynamical stripe orders that display
      density modulation with a long tunable period and high visibility, paving the way
      for the direct experimental observation of a new dynamical supersolidlike state.
      Our scheme for generating STMC can be generalized to other systems and may open
      the door for exploring novel quantum physics and device applications.

PMID- 29219480
TI  - Simulating Positive-Operator-Valued Measures with Projective Measurements.
AB  - Standard projective measurements (PMs) represent a subset of all possible
      measurements in quantum physics, defined by positive-operator-valued measures. We
      study what quantum measurements are projective simulable, that is, can be
      simulated by using projective measurements and classical randomness. We first
      prove that every measurement on a given quantum system can be realized by
      classical randomization of projective measurements on the system plus an ancilla
      of the same dimension. Then, given a general measurement in dimension two or
      three, we show that deciding whether it is PM simulable can be solved by means of
      semidefinite programming. We also establish conditions for the simulation of
      measurements using projective ones valid for any dimension. As an application of
      our formalism, we improve the range of visibilities for which two-qubit Werner
      states do not violate any Bell inequality for all measurements. From an
      implementation point of view, our work provides bounds on the amount of white
      noise a measurement tolerates before losing any advantage over projective ones.

PMID- 29219481
TI  - Weak Gravitational Lensing of Finite Beams.
AB  - The standard theory of weak gravitational lensing relies on the infinitesimal
      light beam approximation. In this context, images are distorted by convergence
      and shear, the respective sources of which unphysically depend on the resolution
      of the distribution of matter-the so-called Ricci-Weyl problem. In this Letter,
      we propose a strong-lensing-inspired formalism to describe the lensing of finite
      beams. We address the Ricci-Weyl problem by showing explicitly that convergence
      is caused by the matter enclosed by the beam, regardless of its distribution.
      Furthermore, shear turns out to be systematically enhanced by the finiteness of
      the beam. This implies, in particular, that the Kaiser-Squires relation between
      shear and convergence is violated, which could have profound consequences on the
      interpretation of weak-lensing surveys.

PMID- 29219482
TI  - Electron Shock Ignition of Inertial Fusion Targets.
AB  - It is shown that inertial confinement fusion targets designed with low implosion
      velocities can be shock-ignited using laser-plasma interaction generated hot
      electrons (hot-e's) to obtain high energy gains. These designs are robust to
      multimode asymmetries and are predicted to ignite even for significantly
      distorted implosions. Electron shock ignition requires tens of kilojoules of hot
      e's which can be produced only at a large laser facility like the National
      Ignition Facility, with the laser-to-hot-e conversion efficiency greater than 10%
      at laser intensities ~10^{16}  W/cm^{2}.

PMID- 29219483
TI  - Quantifying the Coherence between Coherent States.
AB  - In this Letter, we detail an orthogonalization procedure that allows for the
      quantification of the amount of coherence present in an arbitrary superposition
      of coherent states. The present construction is based on the quantum coherence
      resource theory introduced by Baumgratz, Cramer, and Plenio and the coherence
      resource monotone that we identify is found to characterize the nonclassicality
      traditionally analyzed via the Glauber-Sudarshan P distribution. This suggests
      that identical quantum resources underlie both quantum coherence in the discrete
      finite dimensional case and the nonclassicality of quantum light. We show that
      our construction belongs to a family of resource monotones within the framework
      of a resource theory of linear optics, thus establishing deeper connections
      between the class of incoherent operations in the finite dimensional regime and
      linear optical operations in the continuous variable regime.

PMID- 29219484
TI  - Anomalous Quasiparticle Reflection from the Surface of a ^{3}He-^{4}He Dilute
      Solution.
AB  - A free surface of a dilute ^{3}He-^{4}He liquid mixture is a unique system where
      two Fermi liquids with distinct dimensions coexist: a three-dimensional (3D)
      ^{3}He Fermi liquid in the bulk and a two-dimensional (2D) ^{3}He Fermi liquid at
      the surface. To investigate a novel effect generated by the interaction between
      the two Fermi liquids, the mobility of a Wigner crystal of electrons formed on
      the free surface of the mixture is studied. An anomalous enhancement of the
      mobility, compared with the case where the 3D and 2D systems do not interact with
      each other, is observed. The enhancement is explained by the nontrivial
      reflection of 3D quasiparticles from the surface covered with the 2D ^{3}He
      system.

PMID- 29219485
TI  - Efficient Simulation of Quantum Error Correction Under Coherent Error Based on
      the Nonunitary Free-Fermionic Formalism.
AB  - In order to realize fault-tolerant quantum computation, a tight evaluation of the
      error threshold under practical noise models is essential. While non-Clifford
      noise is ubiquitous in experiments, the error threshold under non-Clifford noise
      cannot be efficiently treated with known approaches. We construct an efficient
      scheme for estimating the error threshold of the one-dimensional quantum
      repetition code under non-Clifford noise. To this end, we employ the nonunitary
      free-fermionic formalism for efficient simulation of the one-dimensional
      repetition code under coherent noise. This allows us to evaluate the effect of
      coherence in noise on the error threshold without any approximation. The result
      shows that the error threshold becomes one-third when the noise is fully
      coherent. Our scheme is also applicable to the surface code undergoing a specific
      coherent noise model. The dependence of the error threshold on noise coherence
      can be explained with a leading-order analysis with respect to coherence terms in
      the noise map. We expect that this analysis is also valid for the surface code
      since it is a two-dimensional extension of the one-dimensional repetition code.
      Moreover, since the obtained threshold is accurate, our results can be used as a
      benchmark for the approximation or heuristic schemes for non-Clifford noise.

PMID- 29219486
TI  - Suppression of Ion-Scale Microtearing Modes by Electron-Scale Turbulence via
      Cross-Scale Nonlinear Interactions in Tokamak Plasmas.
AB  - Gyrokinetic turbulence simulations are applied for the first time to the cross
      scale interactions of microtearing modes (MTMs) and electron-temperature-gradient
      (ETG) modes. The investigation of the fluctuation response in a multiscale
      simulation including both types of instabilities indicates that MTMs are
      suppressed by ETG turbulence. A detailed analysis of nonlinear mode coupling
      reveals that radially localized current-sheet structures of MTMs are strongly
      distorted by fine-scale E*B flows of ETG turbulence. Consequently, electron heat
      transport caused by the magnetic flutter of MTMs is significantly reduced and ETG
      turbulence dominates electron heat transport.

PMID- 29219487
TI  - Optimizing the Frequency of Quantum Error Correction.
AB  - A common assumption is that one applies a fault-tolerant quantum error correction
      (FTQEC) after every gate during quantum computing. However, it is known that this
      is not always optimal, since the FTQEC procedure itself can introduce errors.
      Here we vary the number of logical gates between FTQEC operations given that a
      failure of a postselection condition may cause the FTQEC to be skipped. We derive
      an expression for the logical error rate as a function of the error-correction
      frequency and find the optimal frequency for the application of the FTQEC.
      Furthermore, we show that this is relatively insensitive to the postselection
      failure probability for a large range of such probabilities. We provide an
      example of the application of the analytic expression to the ?7,1,3? Steane code
      and data derived from a Monte Carlo simulation.

PMID- 29219488
TI  - Cancellation Mechanism for Dark-Matter-Nucleon Interaction.
AB  - We consider a simple Higgs portal dark-matter model, where the standard model is
      supplemented with a complex scalar whose imaginary part plays the role of weakly
      interacting massive particle dark matter (DM). We show that the direct DM
      detection cross section vanishes at the tree level and zero momentum transfer due
      to a cancellation by virtue of a softly broken symmetry. This cancellation is
      operative for any mediator masses. As a result, our electroweak-scale dark matter
      satisfies all of the phenomenological constraints quite naturally.

PMID- 29219489
TI  - Glassiness and Heterogeneous Dynamics in Dense Solutions of Ring Polymers.
AB  - Understanding how topological constraints affect the dynamics of polymers in
      solution is at the basis of any polymer theory and it is particularly needed for
      melts of rings. These polymers fold as crumpled and space-filling objects and,
      yet, they display a large number of topological constraints. To understand their
      role, here we systematically probe the response of solutions of rings at various
      densities to "random pinning" perturbations. We show that these perturbations
      trigger non-Gaussian and heterogeneous dynamics, eventually leading to nonergodic
      and glassy behavior. We then derive universal scaling relations for the values of
      solution density and polymer length marking the onset of vitrification in
      unperturbed solutions. Finally, we directly connect the heterogeneous dynamics of
      the rings with their spatial organization and mutual interpenetration. Our
      results suggest that deviations from the typical behavior observed in systems of
      linear polymers may originate from architecture-specific (threading) topological
      constraints.

PMID- 29219490
TI  - Nuclear Matrix Elements for Tests of Local Lorentz Invariance Violation.
AB  - The nuclear matrix elements for the spin operator and the momentum quadrupole
      operator are important for the interpretation of precision atomic physics
      experiments that search for violations of local Lorentz and CPT symmetry and for
      new spin-dependent forces. We use the configuration-interaction nuclear shell
      model and self-consistent mean-field theory to calculate the momentum matrix
      elements for ^{21}Ne, ^{23}Na, ^{133}Cs, ^{173}Yb, and ^{201}Hg. We show that
      these momentum matrix are strongly suppressed by the many-body correlations, in
      contrast to the well-known enhancement of the spatial quadrupole nuclear matrix
      elements.

PMID- 29219491
TI  - Amphoteric Be in GaN: Experimental Evidence for Switching between Substitutional
      and Interstitial Lattice Sites.
AB  - We show that Be exhibits amphoteric behavior in GaN, involving switching between
      substitutional and interstitial positions in the lattice. This behavior is
      observed through the dominance of Be_{Ga} in the positron annihilation signals in
      Be-doped GaN, while the emergence of V_{Ga} at high temperatures is a consequence
      of the Be impurities being driven to interstitial positions. The similarity of
      this behavior to that found for Na and Li in ZnO suggests that this could be a
      universal property of light dopants substituting for heavy cations in compound
      semiconductors.

PMID- 29219492
TI  - Atomic-Level Processes of Shear Band Nucleation in Metallic Glasses.
AB  - The ability to control the plastic deformation of amorphous metals is based on
      the capacity to influence the percolation of the shear transformation zones
      (STZs). Despite the recent research progress, the mechanism of STZ self-assembly
      has so far remained elusive. Here, we identify the structural perturbation
      generated by an STZ in the surrounding material and show how such a perturbation
      triggers the activation of the neighboring STZ. The mechanism is based on the
      autocatalytic generation of successive strong strain and rotation fields, leading
      to STZ percolation and, ultimately, to the formation of a shear band.

PMID- 29219493
TI  - Mirror Protected Dirac Fermions on a Weyl Semimetal NbP Surface.
AB  - The first Weyl semimetal was recently discovered in the NbP class of compounds.
      Although the topology of these novel materials has been identified, the surface
      properties are not yet fully understood. By means of scanning tunneling
      spectroscopy, we find that NbP's (001) surface hosts a pair of Dirac cones
      protected by mirror symmetry. Through our high-resolution spectroscopic
      measurements, we resolve the quantum interference patterns arising from these
      novel Dirac fermions and reveal their electronic structure, including the linear
      dispersions. Our data, in agreement with our theoretical calculations, uncover
      further interesting features of the Weyl semimetal NbP's already exotic surface.
      Moreover, we discuss the similarities and distinctions between the Dirac fermions
      here and those in topological crystalline insulators in terms of symmetry
      protection and topology.

PMID- 29219494
TI  - Competition among Superconducting, Antiferromagnetic, and Charge Orders with
      Intervention by Phase Separation in the 2D Holstein-Hubbard Model.
AB  - Using a variational Monte Carlo method, we study the competition of strong
      electron-electron and electron-phonon interactions in the ground state of the
      Holstein-Hubbard model on a square lattice. At half filling, an extended
      intermediate metallic or weakly superconducting (SC) phase emerges, sandwiched
      between antiferromagnetic and charge order (CO) insulating phases. By carrier
      doping into the CO insulator, the SC order dramatically increases for strong
      electron-phonon couplings, but is largely hampered by wide phase separation (PS)
      regions. Superconductivity is optimized at the border to the PS.

PMID- 29219496
TI  - Early Onset of Kinetic Roughening due to a Finite Step Width in Hematin
      Crystallization.
AB  - The structure of the interface of a growing crystal with its nutrient phase
      largely determines the growth dynamics. We demonstrate that hematin crystals,
      crucial for the survival of malaria parasites, transition from faceted to rough
      growth interfaces at increasing thermodynamic supersaturation DeltaMU. Contrary
      to theoretical predictions and previous observations, this transition occurs at
      moderate values of DeltaMU. Moreover, surface roughness varies nonmonotonically
      with DeltaMU, and the rate constant for rough growth is slower than that
      resulting from nucleation and spreading of layers. We attribute these unexpected
      behaviors to the dynamics of step growth dominated by surface diffusion and the
      loss of identity of nuclei separated by less than the step width w. We put forth
      a general criterion for the onset of kinetic roughening using w as a critical
      length scale.

PMID- 29219497
TI  - Binding Energy of ^{79}Cu: Probing the Structure of the Doubly Magic ^{78}Ni from
      Only One Proton Away.
AB  - The masses of the neutron-rich copper isotopes ^{75-79}Cu are determined using
      the precision mass spectrometer ISOLTRAP at the CERN-ISOLDE facility. The trend
      from the new data differs significantly from that of previous results, offering a
      first accurate view of the mass surface adjacent to the Z=28, N=50 nuclide
      ^{78}Ni and supporting a doubly magic character. The new masses compare very well
      with large-scale shell-model calculations that predict shape coexistence in a
      doubly magic ^{78}Ni and a new island of inversion for Z<28. A coherent picture
      of this important exotic region begins to emerge where excitations across Z=28
      and N=50 form a delicate equilibrium with a spherical mean field.

PMID- 29219498
TI  - Spin Pumping and Shot Noise in Ferrimagnets: Bridging Ferro- and
      Antiferromagnets.
AB  - A combination of novel technological and fundamental physics prospects has
      sparked a huge interest in pure spin transport in magnets, starting with
      ferromagnets and spreading to antiferro- and ferrimagnets. We present a
      theoretical study of spin transport across a ferrimagnet-nonmagnetic conductor
      interface, when a magnetic eigenmode is driven into a coherent state. The
      obtained spin current expression includes intra- as well as cross-sublattice
      terms, both of which are essential for a quantitative understanding of spin
      pumping. The dc current is found to be sensitive to the asymmetry in interfacial
      coupling between the two sublattice magnetizations and the mobile electrons,
      especially for antiferromagnets. We further find that the concomitant shot noise
      provides a useful tool for probing the quasiparticle spin and interfacial
      coupling.

PMID- 29219500
TI  - Supernova Origin of Cosmic Rays from a gamma-Ray Signal in the Constellation III
      Region of the Large Magellanic Cloud.
AB  - Cosmic rays could be produced via shock acceleration powered by supernovae. The
      supernova hypothesis implies that each supernova injects, on average, some
      10^{50}  erg in cosmic rays, while the shock acceleration model predicts a power
      law cosmic ray spectrum with the slope close to 2. Verification of these
      predictions requires measurement of the spectrum and power of cosmic ray
      injection from supernova population(s). Here, we obtain such measurements based
      on gamma-ray observation of the Constellation III region of the Large Magellanic
      Cloud. We show that gamma-ray emission from this young star formation region
      originates from cosmic rays injected by approximately two thousand supernovae,
      rather than by a massive star wind powered by a superbubble predating supernova
      activity. Cosmic ray injection power is found to be (1.1_{-0.2}^{+0.5})*10^{50} 
      erg/supernova (for the estimated interstellar medium density 0.3  cm^{-3}). The
      spectrum is a power law with slope 2.09_{-0.07}^{+0.06}. This agrees with the
      model of particle acceleration at supernova shocks and provides a direct proof of
      the supernova origin of cosmic rays.

PMID- 29219499
TI  - Discovery of ^{72}Rb: A Nuclear Sandbank Beyond the Proton Drip Line.
AB  - In this Letter, the observation of two previously unknown isotopes is presented
      for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed
      event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive
      an upper limit for the ground-state half-life of 81 ns, consistent with the
      previous upper limit of 30 ns. For ^{72}Rb, we have measured a half-life of
      103(22) ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb,
      with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the
      diffuseness of the proton drip line and the possibility of sandbanks to exist
      beyond it. The ^{72}Rb half-life is consistent with a 5^{+}->5/2^{-} proton decay
      with an energy of 800-900 keV, in agreement with the atomic mass evaluation
      proton-separation energy as well as results from the finite-range droplet model
      and shell model calculations using the GXPF1A interaction. However, we cannot
      explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)
      >9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results
      imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.

PMID- 29219501
TI  - Exact Logarithmic Four-Point Functions in the Critical Two-Dimensional Ising
      Model.
AB  - Based on conformal symmetry we propose an exact formula for the four-point
      connectivities of Fortuin-Kasteleyn clusters in the critical Ising model when the
      four points are anchored to the boundary. The explicit solution we found displays
      logarithmic singularities. We check our prediction using Monte Carlo simulations
      on a triangular lattice, showing excellent agreement. Our findings could shed
      further light on the formidable task of the characterization of logarithmic
      conformal field theories and on their relevance in physics.

PMID- 29219502
TI  - Relaxation Dynamics in the Merging of N Independent Condensates.
AB  - Controlled quantum systems such as ultracold atoms can provide powerful platforms
      to study nonequilibrium dynamics of closed many-body quantum systems, especially
      since a complete theoretical description is generally challenging. In this
      Letter, we present a detailed study of the rich out-of-equilibrium dynamics of an
      adjustable number N of uncorrelated condensates after connecting them in a ring
      shaped optical trap. We observe the formation of long-lived supercurrents and
      confirm the scaling of their winding number with N in agreement with the geodesic
      rule. Moreover, we provide insight into the microscopic mechanism that underlies
      the smoothening of the phase profile.

PMID- 29219503
TI  - Collapse and Nonlinear Instability of AdS Space with Angular Momentum.
AB  - We present a numerical study of rotational dynamics in AdS_{5} with equal angular
      momenta in the presence of a complex doublet scalar field. We determine that the
      endpoint of gravitational collapse is a Myers-Perry black hole for high energies
      and a hairy black hole for low energies. We investigate the time scale for
      collapse at low energies E, keeping the angular momenta J?E in anti-de Sitter
      (AdS) length units. We find that the inclusion of angular momenta delays the
      collapse time, but retains a t~1/E scaling. We perturb and evolve rotating boson
      stars, and find that boson stars near AdS space appear stable, but those
      sufficiently far from AdS space are unstable. We find that the dynamics of the
      boson star instability depend on the perturbation, resulting either in collapse
      to a Myers-Perry black hole, or development towards a stable oscillating
      solution.

PMID- 29219495
TI  - Evidence for Isospin Violation and Measurement of CP Asymmetries in B
      >K^{*}(892)gamma.
AB  - We report the first evidence for isospin violation in B->K^{*}gamma and the first
      measurement of the difference of CP asymmetries between B^{+}->K^{*+}gamma and
      B^{0}->K^{*0}gamma. This analysis is based on the data sample containing
      772*10^{6}BB[over -] pairs that was collected with the Belle detector at the KEKB
      energy-asymmetric e^{+}e^{-} collider. We find evidence for the isospin violation
      with a significance of 3.1sigma, Delta_{0+}=[+6.2+/-1.5(stat)+/-0.6(syst)+/
      1.2(f_{+-}/f_{00})]%, where the third uncertainty is due to the uncertainty on
      the fraction of B^{+}B^{-} to B^{0}B[over -]^{0} production in Upsilon(4S)
      decays. The measured value is consistent with predictions of the standard model.
      The result for the difference of CP asymmetries is DeltaA_{CP}=[+2.4+/
      2.8(stat)+/-0.5(syst)]%, consistent with zero. The measured branching fractions
      and CP asymmetries for charged and neutral B meson decays are the most precise to
      date. We also calculate the ratio of branching fractions of B^{0}->K^{*0}gamma to
      B_{s}^{0}->phigamma.

PMID- 29219504
TI  - Detecting Topological Transitions in Two Dimensions by Hamiltonian Evolution.
AB  - We show that the evolution of two-component particles governed by a two
      dimensional spin-orbit lattice Hamiltonian can reveal transitions between
      topological phases. A kink in the mean width of the particle distribution signals
      the closing of the band gap, a prerequisite for a quantum phase transition
      between topological phases. Furthermore, for realistic and experimentally
      motivated Hamiltonians, the density profile in topologically nontrivial phases
      displays characteristic rings in the vicinity of the origin that are absent in
      trivial phases. The results are expected to have an immediate application to
      systems of ultracold atoms and photonic lattices.

PMID- 29219505
TI  - Direct Imaging of a Zero-Field Target Skyrmion and Its Polarity Switch in a
      Chiral Magnetic Nanodisk.
AB  - A target Skyrmion is a flux-closed spin texture that has twofold degeneracy and
      is promising as a binary state in next generation universal memories. Although
      its formation in nanopatterned chiral magnets has been predicted, its observation
      has remained challenging. Here, we use off-axis electron holography to record
      images of target Skyrmions in a 160-nm-diameter nanodisk of the chiral magnet
      FeGe. We compare experimental measurements with numerical simulations,
      demonstrate switching between two stable degenerate target Skyrmion ground states
      that have opposite polarities and rotation senses, and discuss the observed
      switching mechanism.

PMID- 29219506
TI  - Nonspherically Symmetric Collapse in Asymptotically AdS Spacetimes.
AB  - We numerically simulate gravitational collapse in asymptotically anti-de Sitter
      spacetimes away from spherical symmetry. Starting from initial data sourced by a
      massless real scalar field, we solve the Einstein equations with a negative
      cosmological constant in five spacetime dimensions and obtain a family of
      nonspherically symmetric solutions, including those that form two distinct black
      holes on the axis. We find that these configurations collapse faster than
      spherically symmetric ones of the same mass and radial compactness. Similarly,
      they require less mass to collapse within a fixed time.

PMID- 29219507
TI  - Closed-Loop Control of Complex Networks: A Trade-Off between Time and Energy.
AB  - Controlling complex nonlinear networks is largely an unsolved problem at the
      present. Existing works focus either on open-loop control strategies and their
      energy consumptions or on closed-loop control schemes with an infinite-time
      duration. We articulate a finite-time, closed-loop controller with an eye toward
      the physical and mathematical underpinnings of the trade-off between the control
      time and energy as well as their dependence on the network parameters and
      structure. The closed-loop controller is tested on a large number of real systems
      including stem cell differentiation, food webs, random ecosystems, and spiking
      neuronal networks. Our results represent a step forward in developing a rigorous
      and general framework to control nonlinear dynamical networks with a complex
      topology.

PMID- 29219508
TI  - Dirac Fermions with Competing Orders: Non-Landau Transition with Emergent
      Symmetry.
AB  - We consider a model of Dirac fermions in 2+1 dimensions with dynamically
      generated, anticommuting SO(3) Neel and Z_{2} Kekule mass terms that permits sign
      free quantum Monte Carlo simulations. The phase diagram is obtained from finite
      size scaling and includes a direct and continuous transition between the Neel and
      Kekule phases. The fermions remain gapped across the transition, and our data
      support an emergent SO(4) symmetry unifying the two order parameters. While the
      bare symmetries of our model do not allow for spinon-carrying Z_{3} vortices in
      the Kekule mass, the emergent SO(4) invariance permits an interpretation of the
      transition in terms of deconfined quantum criticality. The phase diagram also
      features a tricritical point at which the Neel, Kekule, and semimetallic phases
      meet. The present sign-free approach can be generalized to a variety of other
      mass terms and thereby provides a new framework to study exotic critical
      phenomena.

PMID- 29219509
TI  - Optimal Charge-to-Spin Conversion in Graphene on Transition-Metal
      Dichalcogenides.
AB  - When graphene is placed on a monolayer of semiconducting transition metal
      dichalcogenide (TMD) its band structure develops rich spin textures due to
      proximity spin-orbital effects with interfacial breaking of inversion symmetry.
      In this work, we show that the characteristic spin winding of low-energy states
      in graphene on a TMD monolayer enables current-driven spin polarization, a
      phenomenon known as the inverse spin galvanic effect (ISGE). By introducing a
      proper figure of merit, we quantify the efficiency of charge-to-spin conversion
      and show it is close to unity when the Fermi level approaches the spin minority
      band. Remarkably, at high electronic density, even though subbands with opposite
      spin helicities are occupied, the efficiency decays only algebraically. The giant
      ISGE predicted for graphene on TMD monolayers is robust against disorder and
      remains large at room temperature.

PMID- 29219510
TI  - Spin Fluctuations in the 0.7 Anomaly in Quantum Point Contacts.
AB  - It has been argued that the 0.7 anomaly in quantum point contacts (QPCs) is due
      to an enhanced density of states at the top of the QPC barrier (the van Hove
      ridge), which strongly enhances the effects of interactions. Here, we analyze
      their effect on dynamical quantities. We find that they pin the van Hove ridge to
      the chemical potential when the QPC is subopen, cause a temperature dependence
      for the linear conductance that qualitatively agrees with experiments, strongly
      enhance the magnitude of the dynamical spin susceptibility, and significantly
      lengthen the QPC traversal time. We conclude that electrons traverse the QPC via
      a slowly fluctuating spin structure of finite spatial extent.

PMID- 29219512
TI  - Information Retrieval and Criticality in Parity-Time-Symmetric Systems.
AB  - By investigating information flow between a general parity-time (PT-)symmetric
      non-Hermitian system and an environment, we find that the complete information
      retrieval from the environment can be achieved in the PT-unbroken phase, whereas
      no information can be retrieved in the PT-broken phase. The PT-transition point
      thus marks the reversible-irreversible criticality of information flow, around
      which many physical quantities such as the recurrence time and the
      distinguishability between quantum states exhibit power-law behavior. Moreover,
      by embedding a PT-symmetric system into a larger Hilbert space so that the entire
      system obeys unitary dynamics, we reveal that behind the information retrieval
      lies a hidden entangled partner protected by PT symmetry. Possible experimental
      situations are also discussed.

PMID- 29219516
TI  - Ultrafast and Energy-Efficient Quenching of Spin Order: Antiferromagnetism Beats
      Ferromagnetism.
AB  - By comparing femtosecond laser pulse induced ferro- and antiferromagnetic
      dynamics in one and the same material-metallic dysprosium-we show both to behave
      fundamentally different. Antiferromagnetic order is considerably faster and much
      more efficiently reduced by optical excitation than its ferromagnetic
      counterpart. We assign the fast and extremely efficient process in the
      antiferromagnet to an interatomic transfer of angular momentum within the spin
      system. Our findings imply that this angular momentum transfer channel is
      effective in other magnetic metals with nonparallel spin alignment. They also
      point out a possible route towards energy-efficient spin manipulation for
      magnetic devices.

PMID- 29219514
TI  - Second Harmonic Generation of Unpolarized Light.
AB  - A Mueller tensor mathematical framework was applied for predicting and
      interpreting the second harmonic generation (SHG) produced with an unpolarized
      fundamental beam. In deep tissue imaging through SHG and multiphoton
      fluorescence, partial or complete depolarization of the incident light
      complicates polarization analysis. The proposed framework has the distinct
      advantage of seamlessly merging the purely polarized theory based on the Jones or
      Cartesian susceptibility tensors with a more general Mueller tensor framework
      capable of handling partial depolarized fundamental and/or SHG produced. The
      predictions of the model are in excellent agreement with experimental
      measurements of z-cut quartz and mouse tail tendon obtained with polarized and
      depolarized incident light. The polarization-dependent SHG produced with
      unpolarized fundamental allowed determination of collagen fiber orientation in
      agreement with orthogonal methods based on image analysis. This method has the
      distinct advantage of being immune to birefringence or depolarization of the
      fundamental beam for structural analysis of tissues.

PMID- 29219513
TI  - Sonic Landau Levels and Synthetic Gauge Fields in Mechanical Metamaterials.
AB  - Mechanical strain can lead to a synthetic gauge field that controls the dynamics
      of electrons in graphene sheets as well as light in photonic crystals. Here, we
      show how to engineer an analogous synthetic gauge field for lattice vibrations.
      Our approach relies on one of two strategies: shearing a honeycomb lattice of
      masses and springs or patterning its local material stiffness. As a result,
      vibrational spectra with discrete Landau levels are generated. Upon tuning the
      strength of the gauge field, we can control the density of states and transverse
      spatial confinement of sound in the metamaterial. We also show how this gauge
      field can be used to design waveguides in which sound propagates with robustness
      against disorder as a consequence of the change in topological polarization that
      occurs along a domain wall. By introducing dissipation, we can selectively
      enhance the domain-wall-bound topological sound mode, a feature that may
      potentially be exploited for the design of sound amplification by stimulated
      emission of radiation (SASER, the mechanical analogs of lasers).

PMID- 29219517
TI  - Metal-Exchange Catalysis in the Growth of Sesquioxides: Towards Heterostructures
      of Transparent Oxide Semiconductors.
AB  - We observe that the growth rate of Ga_{2}O_{3} in plasma-assisted molecular beam
      epitaxy can be drastically enhanced by an additional In supply. This enhancement
      is shown to result from a catalytic effect, namely, the rapid formation of
      In_{2}O_{3}, immediately followed by a transformation of In_{2}O_{3} to
      Ga_{2}O_{3} due to an In-Ga interatomic exchange. We derive a simple model that
      quantitatively describes this process as well as its consequences on the
      formation rate of Ga_{2}O_{3}. Moreover, we demonstrate that the catalytic action
      of In_{2}O_{3} allows the synthesis of the metastable hexagonal phase of
      Ga_{2}O_{3}. Since the Ga_{2}O_{3}(0001)/In_{2}O_{3}(111) interface is closely
      lattice matched, this novel growth mode opens a new path for the fabrication of
      sesquioxide heterostructures.

PMID- 29219515
TI  - Persistence of the Z=28 Shell Gap Around ^{78}Ni: First Spectroscopy of ^{79}Cu.
AB  - In-beam gamma-ray spectroscopy of ^{79}Cu is performed at the Radioactive Isotope
      Beam Factory of RIKEN. The nucleus of interest is produced through proton
      knockout from a ^{80}Zn beam at 270  MeV/nucleon. The level scheme up to 4.6 MeV
      is established for the first time and the results are compared to Monte Carlo
      shell-model calculations. We do not observe significant knockout feeding to the
      excited states below 2.2 MeV, which indicates that the Z=28 gap at N=50 remains
      large. The results show that the ^{79}Cu nucleus can be described in terms of a
      valence proton outside a ^{78}Ni core, implying the magic character of the
      latter.

PMID- 29219518
TI  - Dispersive Readout of Adiabatic Phases.
AB  - We propose a protocol for the measurement of adiabatic phases of periodically
      driven quantum systems coupled to an open cavity that enables dispersive readout.
      It turns out that the cavity transmission exhibits peaks at frequencies
      determined by a resonance condition that involves the dynamical and the geometric
      phase. Since these phases scale differently with the driving frequency, one can
      determine them by fitting the peak positions to the theoretically expected
      behavior. For the derivation of the resonance condition and for a numerical
      study, we develop a Floquet theory for the dispersive readout of ac driven
      quantum systems. The feasibility is demonstrated for two test cases that
      generalize Landau-Zener-Stuckelberg-Majorana interference to two-parameter
      driving.

PMID- 29219519
TI  - Vibrational Properties of a Monolayer Silicene Sheet Studied by Tip-Enhanced
      Raman Spectroscopy.
AB  - Combining ultrahigh sensitivity, spatial resolution, and the capability to
      resolve chemical information, tip-enhanced Raman spectroscopy (TERS) is a
      powerful tool to study molecules or nanoscale objects. Here we show that TERS can
      also be a powerful tool in studying two-dimensional materials. We have achieved a
      10^{9} Raman signal enhancement and a 0.5 nm spatial resolution using monolayer
      silicene on Ag(111) as a prototypical 2D material system. Because of the
      selective enhancement on Raman modes with vertical vibrational components in
      TERS, our experiment provides direct evidence of the origination of Raman modes
      in silicene. Furthermore, the ultrahigh sensitivity of TERS allows us to identify
      different vibrational properties of silicene phases, which differ only in the
      bucking direction of the Si-Si bonds. Local vibrational features from defects and
      domain boundaries in silicene can also be identified.

PMID- 29219520
TI  - Focusing and Sorting of Ellipsoidal Magnetic Particles in Microchannels.
AB  - We present a simple method to control the position of ellipsoidal magnetic
      particles in microchannel Poiseuille flow at low Reynolds number using a static
      uniform magnetic field. The magnetic field is utilized to pin the particle
      orientation, and the hydrodynamic interactions between ellipsoids and channel
      walls allow control of the transverse position of the particles. We employ a far
      field hydrodynamic theory and simulations using the boundary element method and
      Brownian dynamics to show how magnetic particles can be focused and segregated by
      size and shape. This is of importance for particle manipulation in lab-on-a-chip
      devices.

PMID- 29219521
TI  - Structural "delta Doping" to Control Local Magnetization in Isovalent Oxide
      Heterostructures.
AB  - Modulation and delta-doping strategies, in which atomically thin layers of
      charged dopants are precisely deposited within a heterostructure, have played
      enabling roles in the discovery of new physical behavior in electronic materials.
      Here, we demonstrate a purely structural "delta-doping" strategy in complex oxide
      heterostructures, in which atomically thin manganite layers are inserted into an
      isovalent manganite host, thereby modifying the local rotations of corner
      connected MnO_{6} octahedra. Combining scanning transmission electron microscopy,
      polarized neutron reflectometry, and density functional theory, we reveal how
      local magnetic exchange interactions are enhanced within the spatially confined
      regions of suppressed octahedral rotations. The combined experimental and
      theoretical results illustrate the potential to utilize noncharge-based
      approaches to "doping" in order to enhance or suppress functional properties
      within spatially confined regions of oxide heterostructures.

PMID- 29219522
TI  - Erratum: All Entangled States Can Demonstrate Nonclassical Teleportation [Phys.
      Rev. Lett. 119, 110501 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.110501.

PMID- 29219523
TI  - Optimal and Robust Quantum Metrology Using Interaction-Based Readouts.
AB  - Useful quantum metrology requires nonclassical states with a high particle number
      and (close to) the optimal exploitation of the state's quantum correlations.
      Unfortunately, the single-particle detection resolution demanded by conventional
      protocols, such as spin squeezing via one-axis twisting, places severe limits on
      the particle number. Additionally, the challenge of finding optimal measurements
      (that saturate the quantum Cramer-Rao bound) for an arbitrary nonclassical state
      limits most metrological protocols to only moderate levels of quantum
      enhancement. "Interaction-based readout" protocols have been shown to allow
      optimal interferometry or to provide robustness against detection noise at the
      expense of optimality. In this Letter, we prove that one has great flexibility in
      constructing an optimal protocol, thereby allowing it to also be robust to
      detection noise. This requires the full probability distribution of outcomes in
      an optimal measurement basis, which is typically easily accessible and can be
      determined from specific criteria we provide. Additionally, we quantify the
      robustness of several classes of interaction-based readouts under realistic
      experimental constraints. We determine that optimal and robust quantum metrology
      is achievable in current spin-squeezing experiments.

PMID- 29219524
TI  - Large-Scale Description of Interacting One-Dimensional Bose Gases: Generalized
      Hydrodynamics Supersedes Conventional Hydrodynamics.
AB  - The theory of generalized hydrodynamics (GHD) was recently developed as a new
      tool for the study of inhomogeneous time evolution in many-body interacting
      systems with infinitely many conserved charges. In this Letter, we show that it
      supersedes the widely used conventional hydrodynamics (CHD) of one-dimensional
      Bose gases. We illustrate this by studying "nonlinear sound waves" emanating from
      initial density accumulations in the Lieb-Liniger model. We show that, at zero
      temperature and in the absence of shocks, GHD reduces to CHD, thus for the first
      time justifying its use from purely hydrodynamic principles. We show that sharp
      profiles, which appear in finite times in CHD, immediately dissolve into a higher
      hierarchy of reductions of GHD, with no sustained shock. CHD thereon fails to
      capture the correct hydrodynamics. We establish the correct hydrodynamic
      equations, which are finite-dimensional reductions of GHD characterized by
      multiple, disjoint Fermi seas. We further verify that at nonzero temperature, CHD
      fails at all nonzero times. Finally, we numerically confirm the emergence of
      hydrodynamics at zero temperature by comparing its predictions with a full
      quantum simulation performed using the NRG-TSA-abacus algorithm. The analysis is
      performed in the full interaction range, and is not restricted to either weak- or
      strong-repulsion regimes.

PMID- 29219525
TI  - Coulomb Correlations Intertwined with Spin and Orbital Excitations in LaCoO_{3}.
AB  - We carried out temperature-dependent (20-550 K) measurements of resonant
      inelastic x-ray scattering on LaCoO_{3} to investigate the evolution of its
      electronic structure across the spin-state crossover. In combination with charge
      transfer multiplet calculations, we accurately quantified the renomalized crystal
      field excitation energies and spin-state populations. We show that the screening
      of the effective on-site Coulomb interaction of 3d electrons is orbital selective
      and coupled to the spin-state crossover in LaCoO_{3}. The results establish that
      the gradual spin-state crossover is associated with a relative change of Coulomb
      energy versus bandwidth, leading to a Mott-type insulator-to-metal transition.

PMID- 29219526
TI  - Surprises in O(N) Models: Nonperturbative Fixed Points, Large N Limits, and
      Multicriticality.
AB  - We find that the multicritical fixed point structure of the O(N) models is much
      more complicated than widely believed. In particular, we find new nonperturbative
      fixed points in three dimensions (d=3) as well as at N=infinity. These fixed
      points come together with an intricate double-valued structure when they are
      considered as functions of d and N. Many features found for the O(N) models are
      shared by the O(N)?O(2) models relevant to frustrated magnetic systems.

PMID- 29219527
TI  - Cusp-Shaped Elastic Creases and Furrows.
AB  - The surfaces of growing biological tissues, swelling gels, and compressed rubbers
      do not remain smooth, but frequently exhibit highly localized inward folds. We
      reveal the morphology of this surface folding in a novel experimental setup,
      which permits us to deform the surface of a soft gel in a controlled fashion. The
      interface first forms a sharp furrow, whose tip size decreases rapidly with
      deformation. Above a critical deformation, the furrow bifurcates to an inward
      folded crease of vanishing tip size. We show experimentally and numerically that
      both creases and furrows exhibit a universal cusp shape, whose width scales like
      y^{3/2} at a distance y from the tip. We provide a similarity theory that
      captures the singular profiles before and after the self-folding bifurcation, and
      derive the length of the fold from finite deformation elasticity.

PMID- 29219528
TI  - Cross-Kerr Nonlinearity for Phonon Counting.
AB  - State measurement of a quantum harmonic oscillator is essential in quantum optics
      and quantum information processing. In a system of trapped ions, we
      experimentally demonstrate the projective measurement of the state of the ions'
      motional mode via an effective cross-Kerr coupling to another motional mode. This
      coupling is induced by the intrinsic nonlinearity of the Coulomb interaction
      between the ions. We spectroscopically resolve the frequency shift of the
      motional sideband of the first mode due to the presence of single phonons in the
      second mode and use it to reconstruct the phonon number distribution of the
      second mode.

PMID- 29219529
TI  - Quantum Depletion of a Homogeneous Bose-Einstein Condensate.
AB  - We measure the quantum depletion of an interacting homogeneous Bose-Einstein
      condensate and confirm the 70-year-old theory of Bogoliubov. The observed
      condensate depletion is reversibly tunable by changing the strength of the
      interparticle interactions. Our atomic homogeneous condensate is produced in an
      optical-box trap, the interactions are tuned via a magnetic Feshbach resonance,
      and the condensed fraction is determined by momentum-selective two-photon Bragg
      scattering.

PMID- 29219530
TI  - Solvable Family of Driven-Dissipative Many-Body Systems.
AB  - Exactly solvable models have played an important role in establishing the
      sophisticated modern understanding of equilibrium many-body physics. Conversely,
      the relative scarcity of solutions for nonequilibrium models greatly limits our
      understanding of systems away from thermal equilibrium. We study a family of
      nonequilibrium models, some of which can be viewed as dissipative analogues of
      the transverse-field Ising model, in that an effectively classical Hamiltonian is
      frustrated by dissipative processes that drive the system toward states that do
      not commute with the Hamiltonian. Surprisingly, a broad and experimentally
      relevant subset of these models can be solved efficiently. We leverage these
      solutions to compute the effects of decoherence on a canonical trapped-ion-based
      quantum computation architecture, and to prove a no-go theorem on steady-state
      phase transitions in a many-body model that can be realized naturally with
      Rydberg atoms or trapped ions.

PMID- 29219531
TI  - Spin-Resolved Spectroscopy of the Yu-Shiba-Rusinov States of Individual Atoms.
AB  - A magnetic atom in a superconducting host induces so-called Yu-Shiba-Rusinov
      (YSR) bound states inside the superconducting energy gap. By combining spin
      resolved scanning tunneling spectroscopy with simulations we demonstrate that the
      pair of peaks associated with the YSR states of an individual Fe atom coupled to
      an oxygen-reconstructed Ta surface gets spin polarized in an external magnetic
      field. As theoretically predicted, the electron and hole parts of the YSR states
      have opposite signs of spin polarizations which keep their spin character when
      crossing the Fermi level through the quantum phase transition. The simulation of
      a YSR state right at the Fermi level reveals zero spin polarization which can be
      used to distinguish such states from Majorana zero modes in chains of YSR atoms.

PMID- 29219532
TI  - Does a Growing Static Length Scale Control the Glass Transition?
AB  - Several theories of the glass transition propose that the structural relaxation
      time tau_{alpha} is controlled by a growing static length scale xi that is
      determined by the free energy landscape but not by the local dynamic rules
      governing its exploration. We argue, based on recent simulations using particle
      radius-swap dynamics, that only a modest factor in the increase in tau_{alpha} on
      approach to the glass transition may stem from the growth of a static length,
      with a vastly larger contribution attributable, instead, to a slowdown of local
      dynamics. This reinforces arguments that we base on the observed strong coupling
      of particle diffusion and density fluctuations in real glasses.

PMID- 29219533
TI  - Photonic Counterparts of Cooper Pairs.
AB  - The microscopic theory of superconductivity raised the disruptive idea that
      electrons couple through the elusive exchange of virtual phonons, overcoming the
      strong Coulomb repulsion to form Cooper pairs. Light is also known to interact
      with atomic vibrations, as, for example, in the Raman effect. We show that photon
      pairs exchange virtual vibrations in transparent media, leading to an effective
      photon-photon interaction identical to that for electrons in the BCS theory of
      superconductivity, in spite of the fact that photons are bosons. In this
      scenario, photons may exchange energy without matching a quantum of vibration of
      the medium. As a result, pair correlations for photons scattered away from the
      Raman resonances are expected to be enhanced. An experimental demonstration of
      this effect is provided here by time-correlated Raman measurements in different
      media. The experimental data confirm our theoretical interpretation of a photonic
      Cooper pairing, without the need for any fitting parameters.

PMID- 29219534
TI  - Enstrophy Cascade in Decaying Two-Dimensional Quantum Turbulence.
AB  - We report evidence for an enstrophy cascade in large-scale point-vortex
      simulations of decaying two-dimensional quantum turbulence. Devising a method to
      generate quantum vortex configurations with kinetic energy narrowly localized
      near a single length scale, the dynamics are found to be well characterized by a
      superfluid Reynolds number Re_{s} that depends only on the number of vortices and
      the initial kinetic energy scale. Under free evolution the vortices exhibit
      features of a classical enstrophy cascade, including a k^{-3} power-law kinetic
      energy spectrum, and constant enstrophy flux associated with inertial transport
      to small scales. Clear signatures of the cascade emerge for N?500 vortices.
      Simulating up to very large Reynolds numbers (N=32 768 vortices), additional
      features of the classical theory are observed: the Kraichnan-Batchelor constant
      is found to converge to C^{'}~1.6, and the width of the k^{-3} range scales as
      Re_{s}^{1/2}.

PMID- 29219536
TI  - Infrared Quantum Information.
AB  - We discuss information-theoretic properties of low-energy photons and gravitons
      in the S matrix. Given an incoming n-particle momentum eigenstate, we demonstrate
      that unobserved soft photons decohere nearly all outgoing momentum superpositions
      of charged particles, while the universality of gravity implies that soft
      gravitons decohere nearly all outgoing momentum superpositions of all the hard
      particles. Using this decoherence, we compute the entanglement entropy of the
      soft bosons and show that it is infrared-finite when the leading divergences are
      resummed in the manner of Bloch and Nordsieck.

PMID- 29219537
TI  - Lattice Thermal Conductivity of Polyethylene Molecular Crystals from First
      Principles Including Nuclear Quantum Effects.
AB  - Molecular crystals such as polyethylene are of intense interest as flexible
      thermal conductors, yet their intrinsic upper limits of thermal conductivity
      remain unknown. Here, we report a study of the vibrational properties and lattice
      thermal conductivity of a polyethylene molecular crystal using an ab initio
      approach that rigorously incorporates nuclear quantum motion and finite
      temperature effects. We obtain a thermal conductivity along the chain direction
      of around 160  W m^{-1} K^{-1} at room temperature, providing a firm upper bound
      for the thermal conductivity of this molecular crystal. Furthermore, we show that
      the inclusion of quantum nuclear effects significantly impacts the thermal
      conductivity by altering the phase space for three-phonon scattering. Our
      computational approach paves the way for ab initio studies and computational
      material discovery of molecular solids free of any adjustable parameters.

PMID- 29219538
TI  - Topological Phase Transitions in Multicomponent Superconductors.
AB  - We study the phase transition between a trivial and a time-reversal-invariant
      topological superconductor in a single-band system. By analyzing the interplay of
      symmetry, topology, and energetics, we show that for a generic normal state band
      structure, the phase transition occurs via extended intermediate phases in which
      even- and odd-parity pairing components coexist. For inversion-symmetric systems,
      the coexistence phase spontaneously breaks time-reversal symmetry. For
      noncentrosymmetric superconductors, the low-temperature intermediate phase is
      time-reversal breaking, while the high-temperature phase preserves time-reversal
      symmetry and has topologically protected line nodes. Furthermore, with
      approximate rotational invariance, the system has an emergent U(1)*U(1) symmetry,
      and novel topological defects, such as half vortex lines binding Majorana
      fermions, can exist. We analytically solve for the dispersion of the Majorana
      fermion and show that it exhibits small and large velocities at low and high
      energies. Relevance of our theory to superconducting pyrochlore oxide
      Cd_{2}Re_{2}O_{7} and half-Heusler materials is discussed.

PMID- 29219539
TI  - Irreversibility of Asymptotic Entanglement Manipulation Under Quantum Operations
      Completely Preserving Positivity of Partial Transpose.
AB  - We demonstrate the irreversibility of asymptotic entanglement manipulation under
      quantum operations that completely preserve the positivity of partial transpose
      (PPT), resolving a major open problem in quantum information theory. Our key tool
      is a new efficiently computable additive lower bound for the asymptotic relative
      entropy of entanglement with respect to PPT states, which can be used to evaluate
      the entanglement cost under local operations and classical communication (LOCC).
      We find that for any rank-two mixed state supporting on the 3?3 antisymmetric
      subspace, the amount of distillable entanglement by PPT operations is strictly
      smaller than one entanglement bit (ebit) while its entanglement cost under PPT
      operations is exactly one ebit. As a by-product, we find that for this class of
      states, both the Rains's bound and its regularization are strictly less than the
      asymptotic relative entropy of entanglement. So, in general, there is no unique
      entanglement measure for the manipulation of entanglement by PPT operations. We
      further show a computable sufficient condition for the irreversibility of
      entanglement distillation by LOCC (or PPT) operations.

PMID- 29219540
TI  - Noncollinear Magnetic Structure and Multipolar Order in Eu_{2}Ir_{2}O_{7}.
AB  - The magnetic properties of the pyrochlore iridate material Eu_{2}Ir_{2}O_{7}
      (5d^{5}) have been studied based on first principles calculations, where the
      crystal field splitting Delta, spin-orbit coupling (SOC) lambda, and Coulomb
      interaction U within Ir 5d orbitals all play significant roles. The ground state
      phase diagram has been obtained with respect to the strength of SOC and Coulomb
      interaction U, where a stable antiferromagnetic ground state with all-in-all-out
      (AIAO) spin structure has been found. In addition, another antiferromagnetic
      state with energy close to AIAO has also been found to be stable. The calculated
      nonlinear magnetization of the two stable states both have the d-wave pattern but
      with a pi/4 phase difference, which can perfectly explain the experimentally
      observed nonlinear magnetization pattern. Compared with the results of the
      nondistorted structure, it turns out that the trigonal lattice distortion is
      crucial for stabilizing the AIAO state in Eu_{2}Ir_{2}O_{7}. Furthermore, besides
      large dipolar moments, we also find considerable octupolar moments in the
      magnetic states.

PMID- 29219541
TI  - Spatiotemporal Self-Organization of Fluctuating Bacterial Colonies.
AB  - We model an enclosed system of bacteria, whose motility-induced phase separation
      is coupled to slow population dynamics. Without noise, the system shows both
      static phase separation and a limit cycle, in which a rising global population
      causes a dense bacterial colony to form, which then declines by local cell death,
      before dispersing to reinitiate the cycle. Adding fluctuations, we find that
      static colonies are now metastable, moving between spatial locations via rare and
      strongly nonequilibrium pathways, whereas the limit cycle becomes almost periodic
      such that after each redispersion event the next colony forms in a random
      location. These results, which hint at some aspects of the biofilm-planktonic
      life cycle, can be explained by combining tools from large deviation theory with
      a bifurcation analysis in which the global population density plays the role of
      control parameter.

PMID- 29219542
TI  - Erratum: Theoretical Description of time-Resolved Photoemission Spectroscopy:
      Application to Pump-Probe Experiments [Phys. Rev. Lett. 102, 136401 (2009)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.102.136401.

PMID- 29219543
TI  - Harvesting Multiqubit Entanglement from Ultrastrong Interactions in Circuit
      Quantum Electrodynamics.
AB  - We analyze a multiqubit circuit QED system in the regime where the qubit-photon
      coupling dominates over the system's bare energy scales. Under such conditions a
      manifold of low-energy states with a high degree of entanglement emerges. Here we
      describe a time-dependent protocol for extracting these quantum correlations and
      converting them into well-defined multipartite entangled states of noninteracting
      qubits. Based on a combination of various ultrastrong-coupling effects, the
      protocol can be operated in a fast and robust manner, while still being
      consistent with experimental constraints on switching times and typical energy
      scales encountered in superconducting circuits. Therefore, our scheme can serve
      as a probe for otherwise inaccessible correlations in strongly coupled circuit
      QED systems. It also shows how such correlations can potentially be exploited as
      a resource for entanglement-based applications.

PMID- 29219545
TI  - Flat Optical Conductivity in ZrSiS due to Two-Dimensional Dirac Bands.
AB  - ZrSiS exhibits a frequency-independent interband conductivity
      sigma(omega)=const(omega)=sigma_{flat} in a broad range from 250 to 2500  cm^{-1}
      (30-300 meV). This makes ZrSiS similar to (quasi-)two-dimensional Dirac electron
      systems, such as graphite and graphene. We assign the flat optical conductivity
      to the transitions between quasi-two-dimensional Dirac bands near the Fermi
      level. In contrast to graphene, sigma_{flat} is not universal but related to the
      length of the nodal line in the reciprocal space, k_{0}. Because of spin-orbit
      coupling, the discussed Dirac bands in ZrSiS possess a small gap Delta, for which
      we determine an upper bound max(Delta)=30  meV from our optical measurements. At
      low temperatures the momentum-relaxation rate collapses, and the characteristic
      length scale of momentum relaxation is of the order of microns below 50 K.

PMID- 29219546
TI  - Improved Limits for Higgs-Portal Dark Matter from LHC Searches.
AB  - Searches for invisible Higgs decays at the Large Hadron Collider constrain dark
      matter Higgs-portal models, where dark matter interacts with the standard model
      fields via the Higgs boson. While these searches complement dark matter direct
      detection experiments, a comparison of the two limits depends on the coupling of
      the Higgs boson to the nucleons forming the direct-detection nuclear target,
      typically parametrized in a single quantity f_{N}. We evaluate f_{N} using recent
      phenomenological and lattice-QCD calculations, and include for the first time the
      coupling of the Higgs boson to two nucleons via pion-exchange currents. We
      observe a partial cancellation for Higgs-portal models that makes the two-nucleon
      contribution anomalously small. Our results, summarized as f_{N}=0.308(18), show
      that the uncertainty of the Higgs-nucleon coupling has been vastly overestimated
      in the past. The improved limits highlight that state-of-the-art nuclear physics
      input is key to fully exploiting experimental searches.

PMID- 29219547
TI  - Dark Matter Detection Using Helium Evaporation and Field Ionization.
AB  - We describe a method for dark matter detection based on the evaporation of helium
      atoms from a cold surface and their subsequent detection using field ionization.
      When a dark matter particle scatters off a nucleus of the target material,
      elementary excitations (phonons or rotons) are produced. Excitations which have
      an energy greater than the binding energy of helium to the surface can result in
      the evaporation of helium atoms. We propose to detect these atoms by ionizing
      them in a strong electric field. Because the binding energy of helium to surfaces
      can be below 1 meV, this detection scheme opens up new possibilities for the
      detection of dark matter particles in a mass range down to 1  MeV/c^{2}.

PMID- 29219548
TI  - Janicevic et al. Reply.

PMID- 29219544
TI  - Energy Spectrum of Cosmic-Ray Electron and Positron from 10 GeV to 3 TeV Observed
      with the Calorimetric Electron Telescope on the International Space Station.
AB  - First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV
      is presented based upon observations with the CALET instrument on the
      International Space Station starting in October, 2015. Nearly a half million
      electron and positron events are included in the analysis. CALET is an all
      calorimetric instrument with total vertical thickness of 30 X_{0} and a fine
      imaging capability designed to achieve a large proton rejection and excellent
      energy resolution well into the TeV energy region. The observed energy spectrum
      over 30 GeV can be fit with a single power law with a spectral index of -3.152+/
      0.016 (stat+syst). Possible structure observed above 100 GeV requires further
      investigation with increased statistics and refined data analysis.

PMID- 29219550
TI  - 10-Qubit Entanglement and Parallel Logic Operations with a Superconducting
      Circuit.
AB  - Here we report on the production and tomography of genuinely entangled
      Greenberger-Horne-Zeilinger states with up to ten qubits connecting to a bus
      resonator in a superconducting circuit, where the resonator-mediated qubit-qubit
      interactions are used to controllably entangle multiple qubits and to operate on
      different pairs of qubits in parallel. The resulting 10-qubit density matrix is
      probed by quantum state tomography, with a fidelity of 0.668+/-0.025. Our results
      demonstrate the largest entanglement created so far in solid-state architectures
      and pave the way to large-scale quantum computation.

PMID- 29219551
TI  - Response of the Lattice across the Filling-Controlled Mott Metal-Insulator
      Transition of a Rare Earth Titanate.
AB  - The lattice response of a prototype Mott insulator, SmTiO_{3}, to hole doping is
      investigated with atomic-scale spatial resolution. SmTiO_{3} films are doped with
      Sr on the Sm site with concentrations that span the insulating and metallic sides
      of the filling-controlled Mott metal-insulator transition (MIT). The GdFeO_{3}
      type distortions are investigated using an atomic resolution scanning
      transmission electron microscopy technique that can resolve small lattice
      distortions with picometer precision. We show that these distortions are
      gradually and uniformly reduced as the Sr concentration is increased without any
      phase separation. Significant distortions persist into the metallic state. The
      results present a new picture of the physics of this prototype filling-controlled
      MIT, which is discussed.

PMID- 29219552
TI  - Exploiting Coherence in Nonlinear Spin-Superfluid Transport.
AB  - We show how the interference between superfluid spin currents can endow spin
      circuits with coherent logic functionality. While the hydrodynamic aspects of the
      linear-response collective spin transport obviate interference features, we focus
      on the nonlinear regime, where the critical supercurrent is sensitive to the
      phase accumulated by the condensate in a loop geometry. We propose to control
      this phase by electrical gating that tunes the spin-condensate coherence length.
      The nonlinear aspects of the spin superfluidity thus naturally lend themselves to
      the construction of logic gates, uniquely exploiting the coherence of collective
      spin currents. Vice versa, this functionality can be used to reveal the
      fundamental properties of spin superfluids.

PMID- 29219553
TI  - Quantum Phase Transitions of the Majorana Toric Code in the Presence of Finite
      Cooper-Pair Tunneling.
AB  - The toric code based on Majorana fermions on mesoscopic superconducting islands
      is a promising candidate for quantum information processing. In the limit of
      vanishing Cooper-pair tunneling, it has been argued that the phase transition
      separating the topologically ordered phase of the toric code from the trivial one
      is in the universality class of the (2+1)D XY model. On the other hand, in the
      limit of infinitely large Cooper-pair tunneling, the phase transition is in the
      universality class of the (2+1)D Ising model. In this work, we treat the case of
      finite Cooper-pair tunneling and address the question of how the continuous XY
      symmetry breaking phase transition turns into a discrete Z_{2} symmetry breaking
      one when the Cooper-pair tunneling rate is increased. We show that this happens
      through a couple of tricritical points and first order phase transitions. Using a
      Jordan-Wigner transformation, we map the problem to that of spins coupled to
      quantum rotors and subsequently, propose a Landau field theory for this model
      that matches the known results in the respective limits. We calculate the
      effective field theories and provide the relevant critical exponents for the
      different phase transitions. Our results are relevant for predicting the
      stability of the topological phase in realistic experimental implementations.

PMID- 29219554
TI  - Supercurrent Interference in Few-Mode Nanowire Josephson Junctions.
AB  - Junctions created by coupling two superconductors via a semiconductor nanowire in
      the presence of high magnetic fields are the basis for the potential detection,
      fusion, and braiding of Majorana bound states. We study NbTiN/InSb nanowire/NbTiN
      Josephson junctions and find that the dependence of the critical current on the
      magnetic field exhibits gate-tunable nodes. This is in contrast with a well-known
      Fraunhofer effect, under which critical current nodes form a regular pattern with
      a period fixed by the junction area. Based on a realistic numerical model we
      conclude that the Zeeman effect induced by the magnetic field and the spin-orbit
      interaction in the nanowire are insufficient to explain the observed evolution of
      the Josephson effect. We find the interference between the few occupied one
      dimensional modes in the nanowire to be the dominant mechanism responsible for
      the critical current behavior. We also report a strong suppression of critical
      currents at finite magnetic fields that should be taken into account when
      designing circuits based on Majorana bound states.

PMID- 29219555
TI  - Experimental Observation of a Current-Driven Instability in a Neutral Electron
      Positron Beam.
AB  - We report on the first experimental observation of a current-driven instability
      developing in a quasineutral matter-antimatter beam. Strong magnetic fields (>=1 
      T) are measured, via means of a proton radiography technique, after the
      propagation of a neutral electron-positron beam through a background electron-ion
      plasma. The experimentally determined equipartition parameter of epsilon_{B}~10^{
      3} is typical of values inferred from models of astrophysical gamma-ray bursts,
      in which the relativistic flows are also expected to be pair dominated. The data,
      supported by particle-in-cell simulations and simple analytical estimates,
      indicate that these magnetic fields persist in the background plasma for
      thousands of inverse plasma frequencies. The existence of such long-lived
      magnetic fields can be related to analog astrophysical systems, such as those
      prevalent in lepton-dominated jets.

PMID- 29219556
TI  - Probing Intrinsic Properties of Short Gamma-Ray Bursts with Gravitational Waves.
AB  - Progenitors of short gamma-ray bursts are thought to be neutron stars coalescing
      with their companion black hole or neutron star, which are one of the main
      gravitational wave sources. We have devised a Bayesian framework for combining
      gamma-ray burst and gravitational wave information that allows us to probe short
      gamma-ray burst luminosities. We show that combined short gamma-ray burst and
      gravitational wave observations not only improve progenitor distance and
      inclination angle estimates, they also allow the isotropic luminosities of short
      gamma-ray bursts to be determined without the need for host galaxy or light-curve
      information. We characterize our approach by simulating 1000 joint short gamma
      ray burst and gravitational wave detections by Advanced LIGO and Advanced Virgo.
      We show that ~90% of the simulations have uncertainties on short gamma-ray burst
      isotropic luminosity estimates that are within a factor of two of the ideal
      scenario, where the distance is known exactly. Therefore, isotropic luminosities
      can be confidently determined for short gamma-ray bursts observed jointly with
      gravitational waves detected by Advanced LIGO and Advanced Virgo. Planned
      enhancements to Advanced LIGO will extend its range and likely produce several
      joint detections of short gamma-ray bursts and gravitational waves. Third
      generation gravitational wave detectors will allow for isotropic luminosity
      estimates for the majority of the short gamma-ray burst population within a
      redshift of z~1.

PMID- 29219558
TI  - Analog Quantum Error Correction with Encoding a Qubit into an Oscillator.
AB  - To implement fault-tolerant quantum computation with continuous variables,
      Gottesman-Kitaev-Preskill (GKP) qubits have been recognized as an important
      technological element. However, the analog outcome of GKP qubits, which includes
      beneficial information to improve the error tolerance, has been wasted, because
      the GKP qubits have been treated as only discrete variables. In this Letter, we
      propose a hybrid quantum error correction approach that combines digital
      information with the analog information of the GKP qubits using a maximum
      likelihood method. As an example, we demonstrate that the three-qubit bit-flip
      code can correct double errors, whereas the conventional method based on majority
      voting on the binary measurement outcome can correct only a single error. As
      another example, we show that a concatenated code known as Knill's C_{4}/C_{6}
      code can achieve the hashing bound for the quantum capacity of the Gaussian
      quantum channel (GQC). To the best of our knowledge, this approach is the first
      attempt to draw both digital and analog information to improve quantum error
      correction performance and achieve the hashing bound for the quantum capacity of
      the GQC.

PMID- 29219557
TI  - Intertwined Order and Holography: The Case of Parity Breaking Pair Density Waves.
AB  - We present a minimal bottom-up extension of the Chern-Simons bulk action for
      holographic translational symmetry breaking that naturally gives rise to pair
      density waves. We construct stationary inhomogeneous black hole solutions in
      which both the U(1) symmetry and spatially translational symmetry are
      spontaneously broken at a finite temperature and charge density. This novel
      solution provides a dual description of a superconducting phase intertwined with
      charge, current, and parity orders.

PMID- 29219559
TI  - Emergent Non-Eulerian Hydrodynamics of Quantum Vortices in Two Dimensions.
AB  - We develop a coarse-grained description of the point-vortex model, finding that a
      large number of planar vortices and antivortices behave as an inviscid non
      Eulerian fluid at large scales. The emergent binary vortex fluid is subject to
      anomalous stresses absent from Euler's equation, caused by the singular nature of
      quantum vortices. The binary vortex fluid is compressible, and has an asymmetric
      Cauchy stress tensor allowing orbital angular momentum exchange with the
      vorticity and vortex density. An analytic solution for vortex shear flow driven
      by anomalous stresses is in excellent agreement with numerical simulations of the
      point-vortex model.

PMID- 29219560
TI  - Observation of Electron Bernstein Wave Heating in a Reversed Field Pinch.
AB  - The first observation of rf heating in a reversed field pinch (RFP) using the
      electron Bernstein wave (EBW) is demonstrated on the Madison Symmetric Torus.
      Propagation across and heating in a stochastic magnetic field is observed. Novel
      techniques are required to measure the suprathermal electron tail generated by
      EBW heating in the presence of intense Ohmic heating. rf-heated electrons
      directly probe the edge transport properties in the RFP; measured loss rates
      imply a large noncollisional radial diffusivity.

PMID- 29219561
TI  - Long-Range Order in the Dipolar XY Antiferromagnet Er_{2}Sn_{2}O_{7}.
AB  - Er_{2}Sn_{2}O_{7} remains a puzzling case among the extensively studied
      frustrated compounds of the rare-earth pyrochlore family. Indeed, while a first
      order transition towards a long-range antiferromagnetic state with the so-called
      Palmer-Chalker structure is theoretically predicted, it has not yet been
      observed, leaving the issue as to whether it is a spin-liquid candidate open. We
      report on neutron scattering and magnetization measurements which evidence a
      second-order transition towards this Palmer-Chalker ordered state around 108 mK.
      Extreme care was taken to ensure a proper thermalization of the sample, which has
      proved to be crucial to successfully observe the magnetic Bragg peaks. At the
      transition, a gap opens in the excitations, superimposed on a strong quasielastic
      signal. The exchange parameters, refined from a spin-wave analysis in applied
      magnetic field, confirm that Er_{2}Sn_{2}O_{7} is a realization of the dipolar XY
      pyrochlore antiferromagnet. The proximity of competing phases and the strong XY
      anisotropy of the Er^{3+} magnetic moment might be at the origin of enhanced
      fluctuations, leading to the unexpected nature of the transition, the low
      ordering temperature, and the observed multiscale dynamics.

PMID- 29219562
TI  - Force and Mass Dynamics in Non-Newtonian Suspensions.
AB  - Above a certain solid fraction, dense granular suspensions in water exhibit non
      Newtonian behavior, including impact-activated solidification. Although it has
      been suggested that solidification depends on boundary interactions, quantitative
      experiments on the boundary forces have not been reported. Using high-speed
      video, tracer particles, and photoelastic boundaries, we determine the impactor
      kinematics and the magnitude and timings of impactor-driven events in the body
      and at the boundaries of cornstarch suspensions. We observe mass shocks in the
      suspension during impact. The shock front dynamics are strongly correlated to
      those of the intruder. However, the total momentum associated with this shock
      never approaches the initial impactor momentum. We also observe a faster second
      front associated with the propagation of pressure to the boundaries of the
      suspension. The two fronts depend differently on the initial impactor speed v_{0}
      and the suspension packing fraction. The speed of the pressure wave is at least
      an order of magnitude smaller than (linear) ultrasound speeds obtained for much
      higher frequencies, pointing to complex amplitude and frequency response of
      cornstarch suspensions to compressive strains.

PMID- 29219563
TI  - Experimental Demonstration of Fault-Tolerant State Preparation with
      Superconducting Qubits.
AB  - Robust quantum computation requires encoding delicate quantum information into
      degrees of freedom that are hard for the environment to change. Quantum encodings
      have been demonstrated in many physical systems by observing and correcting
      storage errors, but applications require not just storing information; we must
      accurately compute even with faulty operations. The theory of fault-tolerant
      quantum computing illuminates a way forward by providing a foundation and
      collection of techniques for limiting the spread of errors. Here we implement one
      of the smallest quantum codes in a five-qubit superconducting transmon device and
      demonstrate fault-tolerant state preparation. We characterize the resulting code
      words through quantum process tomography and study the free evolution of the
      logical observables. Our results are consistent with fault-tolerant state
      preparation in a protected qubit subspace.

PMID- 29219564
TI  - Drift-Induced Enhancement of Cubic Dresselhaus Spin-Orbit Interaction in a Two
      Dimensional Electron Gas.
AB  - We investigated the effect of an in-plane electric field on drifting spins in a
      GaAs quantum well. Kerr rotation images of the drifting spins revealed that the
      spin precession wavelength increases with increasing drift velocity regardless of
      the transport direction. A model developed for drifting spins with a heated
      electron distribution suggests that the in-plane electric field enhances the
      effective magnetic field component originating from the cubic Dresselhaus spin
      orbit interaction.

PMID- 29219565
TI  - Streak Camera for Strong-Field Ionization.
AB  - Ionization of an atom or molecule by a strong laser field produces suboptical
      cycle wave packets whose control has given rise to attosecond science. The final
      states of the wave packets depend on ionization and deflection by the laser
      field, which are convoluted in conventional experiments. Here, we demonstrate a
      technique enabling efficient electron deflection, separate from the field driving
      strong-field ionization. Using a midinfrared deflection field permits one to
      distinguish electron wave packets generated at different field maxima of an
      intense few-cycle visible laser pulse. We utilize this capability to trace the
      scattering of low-energy electrons driven by the midinfrared field. Our approach
      represents a general technique for studying and controlling strong-field
      ionization dynamics on the attosecond time scale.

PMID- 29219566
TI  - Dynamical Engineering of Interactions in Qudit Ensembles.
AB  - We propose and analyze a method to engineer effective interactions in an ensemble
      of d-level systems (qudits) driven by global control fields. In particular, we
      present (i) a necessary and sufficient condition under which a given interaction
      can be decoupled, (ii) the existence of a universal sequence that decouples any
      (cancelable) interaction, and (iii) an efficient algorithm to engineer a target
      Hamiltonian from an initial Hamiltonian (if possible). We illustrate the
      potential of this method with two examples. Specifically, we present a 6-pulse
      sequence that decouples effective spin-1 dipolar interactions and demonstrate
      that a spin-1 Ising chain can be engineered to study transitions among three
      distinct symmetry protected topological phases. Our work enables new approaches
      for the realization of both many-body quantum memories and programmable analog
      quantum simulators using existing experimental platforms.

PMID- 29219567
TI  - CP Asymmetries in Charm Decays into Neutral Kaons.
AB  - We find a new CP-violation effect in charm decays into neutral kaons, which
      results from the interference between two tree (Cabibbo-favored and doubly
      Cabibbo-suppressed) amplitudes with the mixing of final-state mesons. This
      effect, estimated to be of an order of 10^{-3}, is much larger than the direct CP
      asymmetries in these decays, but missed in the literature. It can be revealed by
      measuring the difference of the time-dependent CP asymmetries in the D^{+}
      >pi^{+}K_{S}^{0} and D_{s}^{+}->K^{+}K_{S}^{0} modes, which are accessible at the
      LHCb and Belle II experiments. If confirmed, the new effect has to be taken into
      account, as the above direct CP asymmetries are used to search for new physics.

PMID- 29219568
TI  - Symmetry-Protected Topological States for Interacting Fermions in Alkaline-Earth
      Like Atoms.
AB  - We discuss the quantum simulation of symmetry-protected topological (SPT) states
      for interacting fermions in quasi-one-dimensional gases of alkaline-earth-like
      atoms such as ^{173}Yb. Taking advantage of the separation of orbital and nuclear
      spin degrees of freedom in these atoms, we consider Raman-assisted spin-orbit
      couplings in the clock states, which, together with the spin-exchange
      interactions in the clock-state manifolds, give rise to SPT states for
      interacting fermions. We numerically investigate the phase diagram of the system,
      and study the phase transitions between the SPT phase and the symmetry-breaking
      phases. The interaction-driven topological phase transition can be probed by
      measuring local density distribution of the topological edge modes.

PMID- 29219569
TI  - Giant Kovacs-Like Memory Effect for Active Particles.
AB  - Dynamical properties of self-propelled particles obeying a bounded confidence
      rule are investigated by means of kinetic theory and agent-based simulations.
      While memory effects are observed in disordered systems, we show that they also
      occur in active matter systems. In particular, we find that the system exhibits a
      giant Kovacs-like memory effect that is much larger than predicted by a generic
      linear theory. Based on a separation of time scales we develop a nonlinear theory
      to explain this effect. We apply this theory to driven granular gases and propose
      further applications to spin glasses.

PMID- 29219570
TI  - Enhancing High Harmonic Output in Solids through Quantum Confinement.
AB  - We investigate theoretically the effect of quantum confinement on high harmonic
      generation (HHG) in semiconductors by systematically varying the width of a model
      quantum nanowire. Our analysis reveals a reduction in ionization and a concurrent
      growth in HHG efficiency with increasing confinement. The drop in ionization
      results from an increase in the band gap due to stronger confinement. The
      increase in harmonic efficiency comes as a result of the confinement restricting
      the spreading of the transverse wave packet. As a result, intense laser driven 1D
      and 2D nanosystems present a potential pathway to increasing yield and photon
      energy of HHG in solids.

PMID- 29219571
TI  - Disorder-Induced Topological State Transition in Photonic Metamaterials.
AB  - The topological state transition has been widely studied based on the quantized
      topological band invariant such as the Chern number for the system without
      intense randomness that may break the band structures. We numerically demonstrate
      the disorder-induced state transition in the photonic topological systems for the
      first time. Instead of applying the ill-defined topological band invariant in a
      disordered system, we utilize an empirical parameter to unambiguously illustrate
      the state transition of the topological metamaterials. Before the state
      transition, we observe a robust surface state with well-confined electromagnetic
      waves propagating unidirectionally, immune to the disorder from permittivity
      fluctuation up to 60% of the original value. During the transition, a hybrid
      state composed of a quasiunidirectional surface mode and intensively localized
      hot spots is established, a result of the competition between the topological
      protection and Anderson localization.

PMID- 29219573
TI  - Qubit-Assisted Transduction for a Detection of Surface Acoustic Waves near the
      Quantum Limit.
AB  - We demonstrate ultrasensitive measurement of fluctuations in a surface-acoustic
      wave (SAW) resonator using a hybrid quantum system consisting of the SAW
      resonator, a microwave (MW) resonator, and a superconducting qubit. The
      nonlinearity of the driven qubit induces parametric coupling, which up-converts
      the excitation in the SAW resonator to that in the MW resonator. Thermal
      fluctuations of the SAW resonator near the quantum limit are observed in the
      noise spectroscopy in the MW domain.

PMID- 29219572
TI  - Limits on Axion Couplings from the First 80 Days of Data of the PandaX-II
      Experiment.
AB  - We report new searches for solar axions and galactic axionlike dark matter
      particles, using the first low-background data from the PandaX-II experiment at
      China Jinping Underground Laboratory, corresponding to a total exposure of about
      2.7*10^{4}  kg day. No solar axion or galactic axionlike dark matter particle
      candidate has been identified. The upper limit on the axion-electron coupling
      (g_{Ae}) from the solar flux is found to be about 4.35*10^{-12} in the mass range
      from 10^{-5} to 1  keV/c^{2} with 90% confidence level, similar to the recent LUX
      result. We also report a new best limit from the ^{57}Fe deexcitation. On the
      other hand, the upper limit from the galactic axions is on the order of 10^{-13}
      in the mass range from 1 to 10  keV/c^{2} with 90% confidence level, slightly
      improved compared with the LUX.

PMID- 29219574
TI  - Hidden Order and Symmetry Protected Topological States in Quantum Link Ladders.
AB  - We show that, whereas spin-1/2 one-dimensional U(1) quantum-link models (QLMs)
      are topologically trivial, when implemented in ladderlike lattices these models
      may present an intriguing ground-state phase diagram, which includes a symmetry
      protected topological (SPT) phase that may be readily revealed by analyzing long
      range string spin correlations along the ladder legs. We propose a simple scheme
      for the realization of spin-1/2 U(1) QLMs based on single-component fermions
      loaded in an optical lattice with s and p bands, showing that the SPT phase may
      be experimentally realized by adiabatic preparation.

PMID- 29219575
TI  - Comment on "Interevent Correlations from Avalanches Hiding Below the Detection
      Threshold".

PMID- 29219576
TI  - Publisher's Note: Investigating Anisotropic Quantum Hall States with Bimetric
      Geometry [Phys. Rev. Lett. 119, 146602 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.146602.

PMID- 29219577
TI  - Publisher's Note: Observation of Optomechanical Strain in a Cold Atomic Cloud
      [Phys. Rev. Lett. 119, 163201 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.163201.

PMID- 29219578
TI  - Emergent versus Individual-Based Multicellular Chemotaxis.
AB  - Multicellular chemotaxis can occur via individually chemotaxing cells that are
      mechanically coupled. Alternatively, it can emerge collectively, from cells
      chemotaxing differently in a group than they would individually. Here we consider
      collective movement that emerges from cells on the exterior of the collective
      responding to chemotactic signals, whereas bulk cells remain uninvolved in
      sensing and directing the collective. We find that the precision of this type of
      emergent chemotaxis is higher than that of individual-based chemotaxis for one
      dimensional cell chains and two-dimensional cell sheets, but not three
      dimensional cell clusters. We describe the physical origins of these results,
      discuss their biological implications, and show how they can be tested using
      common experimental measures such as the chemotactic index.

PMID- 29219579
TI  - Entanglement and Wigner Function Negativity of Multimode Non-Gaussian States.
AB  - Non-Gaussian operations are essential to exploit the quantum advantages in
      optical continuous variable quantum information protocols. We focus on mode
      selective photon addition and subtraction as experimentally promising processes
      to create multimode non-Gaussian states. Our approach is based on correlation
      functions, as is common in quantum statistical mechanics and condensed matter
      physics, mixed with quantum optics tools. We formulate an analytical expression
      of the Wigner function after the subtraction or addition of a single photon, for
      arbitrarily many modes. It is used to demonstrate entanglement properties
      specific to non-Gaussian states and also leads to a practical and elegant
      condition for Wigner function negativity. Finally, we analyze the potential of
      photon addition and subtraction for an experimentally generated multimode
      Gaussian state.

PMID- 29219580
TI  - RNA Base Pairing Determines the Conformations of RNA Inside Spherical Viruses.
AB  - Many simple RNA viruses enclose their genetic material by a protein shell called
      the capsid. While the capsid structures are well characterized for most viruses,
      the structure of RNA inside the shells and the factors contributing to it remain
      poorly understood. We study the impact of base pairing on the conformations of
      RNA and find that it undergoes a swollen coil to globule continuous transition as
      a function of the strength of the pairing interaction. We also observe a first
      order transition and kink profile as a function of RNA length. All these
      transitions could explain the different RNA profiles observed inside viral
      shells.

PMID- 29219581
TI  - Quantized Magnetization Density in Periodically Driven Systems.
AB  - We study micromotion in two-dimensional periodically driven systems in which all
      bulk Floquet eigenstates are localized by disorder. We show that this micromotion
      gives rise to a quantized time-averaged orbital magnetization density in any
      region completely filled with fermions. The quantization of magnetization density
      has a topological origin, and reveals the physical nature of the new phase
      identified in P. Titum, E. Berg, M. S. Rudner, G. Refael, and N. H. Lindner
      [Phys. Rev. X 6, 021013 (2016)PRXHAE2160-330810.1103/PhysRevX.6.021013]. We thus
      establish that the topological index of this phase can be accessed directly in
      bulk measurements, and propose an experimental protocol to do so using
      interferometry in cold-atom-based realizations.

PMID- 29219582
TI  - Fast Nondestructive Parallel Readout of Neutral Atom Registers in Optical
      Potentials.
AB  - We demonstrate the parallel and nondestructive readout of the hyperfine state for
      optically trapped ^{87}Rb atoms. The scheme is based on state-selective
      fluorescence imaging and achieves detection fidelities >98% within 10 ms, while
      keeping 99% of the atoms trapped. For the readout of dense arrays of neutral
      atoms in optical lattices, where the fluorescence images of neighboring atoms
      overlap, we apply a novel image analysis technique using Bayesian inference to
      determine the internal state of multiple atoms. Our method is scalable to large
      neutral atom registers relevant for future quantum information processing tasks
      requiring fast and nondestructive readout and can also be used for the
      simultaneous readout of quantum information stored in internal qubit states and
      in the atoms' positions.

PMID- 29219583
TI  - Comment on "Theoretical Confirmation of the Low Experimental 3C/3D f-Value Ratio
      in Fe xvii".
AB  - A Comment on the Letter by Mendoza and Bautista [Phys. Rev. Lett. 118, 163002
      (2017)PRLTAO0031-900710.1103/PhysRevLett.118.163002].

PMID- 29219584
TI  - Spin-Polarized Current in Noncollinear Antiferromagnets.
AB  - Noncollinear antiferromagnets, such as Mn_{3}Sn and Mn_{3}Ir, were recently shown
      to be analogous to ferromagnets in that they have a large anomalous Hall effect.
      Here we show that these materials are similar to ferromagnets in another aspect:
      the charge current in these materials is spin polarized. In addition, we show
      that the same mechanism that leads to the spin-polarized current also leads to a
      transverse spin current, which has a distinct symmetry and origin from the
      conventional spin Hall effect. We illustrate the existence of the spin-polarized
      current and the transverse spin current by performing ab initio microscopic
      calculations and by analyzing the symmetry. We discuss possible applications of
      these novel spin currents, such as an antiferromagnetic metallic or tunneling
      junction.

PMID- 29219585
TI  - Test of the Brink-Axel Hypothesis for the Pygmy Dipole Resonance.
AB  - The gamma strength function and level density of 1^{-} states in ^{96}Mo have
      been extracted from a high-resolution study of the (p[over ->], p[over ->]^{'})
      reaction at 295 MeV and extreme forward angles. By comparison with compound
      nucleus gamma decay experiments, this allows a test of the generalized Brink-Axel
      hypothesis in the energy region of the pygmy dipole resonance. The Brink-Axel
      hypothesis is commonly assumed in astrophysical reaction network calculations and
      states that the gamma strength function in nuclei is independent of the structure
      of the initial and final state. The present results validate the Brink-Axel
      hypothesis for ^{96}Mo and provide independent confirmation of the methods used
      to separate gamma strength function and level density in gamma decay experiments.

PMID- 29219586
TI  - Intersubband Landau Level Couplings Induced by In-Plane Magnetic Fields in
      Trilayer Graphene.
AB  - We observed broken-symmetry quantum Hall effects and level crossings between spin
      and valley- resolved Landau levels (LLs) in Bernal stacked trilayer graphene.
      When the magnetic field was tilted with respect to the sample normal from 0
      degrees  to 66 degrees , the LL crossings formed at intersections of zeroth and
      second LLs from monolayer-graphene-like and bilayer-graphene-like subbands,
      respectively, exhibited a sequence of transitions. The results indicate the LLs
      from different subbands are coupled by in-plane magnetic fields (B_{?}), which
      was explained by developing the tight-binding model Hamiltonian of trilayer
      graphene under B_{?}.

PMID- 29219549
TI  - Search for Baryon-Number Violating Xi_{b}^{0} Oscillations.
AB  - A search for baryon-number violating Xi_{b}^{0} oscillations is performed with a
      sample of pp collision data recorded by the LHCb experiment, corresponding to an
      integrated luminosity of 3  fb^{-1}. The baryon number at the moment of
      production is identified by requiring that the Xi_{b}^{0} come from the decay of
      a resonance Xi_{b}^{*-}->Xi_{b}^{0}pi^{-} or Xi_{b}^{'-}->Xi_{b}^{0}pi^{-}, and
      the baryon number at the moment of decay is identified from the final state using
      the decays Xi_{b}^{0}->Xi_{c}^{+}pi^{-},Xi_{c}^{+}->pK^{-}pi^{+}. No evidence of
      baryon-number violation is found, and an upper limit at the 95% confidence level
      is set on the oscillation rate of omega<0.08  ps^{-1}, where omega is the
      associated angular frequency.

PMID- 29219587
TI  - Critical Spin Superflow in a Spinor Bose-Einstein Condensate.
AB  - We investigate the critical dynamics of spin superflow in an easy-plane
      antiferromagnetic spinor Bose-Einstein condensate. Spin-dipole oscillations are
      induced in a trapped condensate by applying a linear magnetic field gradient and
      we observe that the damping rate increases rapidly as the field gradient
      increases above a certain critical value. The onset of dissipation is found to be
      associated with the generation of dark-bright solitons due to the modulation
      instability of the counterflow of two spin components. Spin turbulence emerges as
      the solitons decay because of their snake instability. We identify another
      critical point for spin superflow, in which transverse magnon excitations are
      dynamically generated via spin-exchanging collisions, which leads to the
      transient formation of axial polar spin domains.

PMID- 29219588
TI  - Effect of Weak Binding on the Apparent Spin-Orbit Splitting in Nuclei.
AB  - The apparent splitting between orbitals that are spin-orbit partners can be
      substantially influenced by the effects of weak binding. In particular, such
      effects can account for the observed decrease in separation of the neutron
      1p_{3/2} and 1p_{1/2} orbitals between the ^{41}Ca and ^{35}Si isotopes. This
      behavior has been the subject of recent experimental and theoretical works and
      cited as evidence for a proton "bubble" in ^{34}Si causing an explicit weakening
      of the spin-orbit interaction. The results reported here suggest that the change
      in the separation between the 1p_{3/2} and 1p_{1/2} partners occurs dominantly
      because of the behavior of the energies of these 1p neutron states near zero
      binding.

PMID- 29219590
TI  - High-Dimensional Single-Photon Quantum Gates: Concepts and Experiments.
AB  - Transformations on quantum states form a basic building block of every quantum
      information system. From photonic polarization to two-level atoms, complete sets
      of quantum gates for a variety of qubit systems are well known. For multilevel
      quantum systems beyond qubits, the situation is more challenging. The orbital
      angular momentum modes of photons comprise one such high-dimensional system for
      which generation and measurement techniques are well studied. However, arbitrary
      transformations for such quantum states are not known. Here we experimentally
      demonstrate a four-dimensional generalization of the Pauli X gate and all of its
      integer powers on single photons carrying orbital angular momentum. Together with
      the well-known Z gate, this forms the first complete set of high-dimensional
      quantum gates implemented experimentally. The concept of the X gate is based on
      independent access to quantum states with different parities and can thus be
      generalized to other photonic degrees of freedom and potentially also to other
      quantum systems.

PMID- 29219591
TI  - Measurement of the Vector and Tensor Asymmetries at Large Missing Momentum in
      Quasielastic (e[over ->],e^{'}p) Electron Scattering from Deuterium.
AB  - We report the measurement of the beam-vector and tensor asymmetries A_{ed}^{V}
      and A_{d}^{T} in quasielastic (e[over ->],e^{'}p) electrodisintegration of the
      deuteron at the MIT-Bates Linear Accelerator Center up to missing momentum of 500
      MeV/c. Data were collected simultaneously over a momentum transfer range
      0.1<Q^{2}<0.5  (GeV/c)^{2} with the Bates Large Acceptance Spectrometer Toroid
      using an internal deuterium gas target polarized sequentially in both vector and
      tensor states. The data are compared with calculations. The beam-vector asymmetry
      A_{ed}^{V} is found to be directly sensitive to the D-wave component of the
      deuteron and has a zero crossing at a missing momentum of about 320  MeV/c, as
      predicted. The tensor asymmetry A_{d}^{T} at large missing momentum is found to
      be dominated by the influence of the tensor force in the neutron-proton final
      state interaction. The new data provide a strong constraint on theoretical
      models.

PMID- 29219594
TI  - Phase Competition in the Palmer-Chalker XY Pyrochlore Er_{2}Pt_{2}O_{7}.
AB  - We report neutron scattering measurements on Er_{2}Pt_{2}O_{7}, a new addition to
      the XY family of frustrated pyrochlore magnets. Symmetry analysis of our elastic
      scattering data shows that Er_{2}Pt_{2}O_{7} orders into the k=0, Gamma_{7}
      magnetic structure (the Palmer-Chalker state), at T_{N}=0.38  K. This contrasts
      with its sister XY pyrochlore antiferromagnets Er_{2}Ti_{2}O_{7} and
      Er_{2}Ge_{2}O_{7}, both of which order into Gamma_{5} magnetic structures at much
      higher temperatures, T_{N}=1.2 and 1.4 K, respectively. In this temperature
      range, the magnetic heat capacity of Er_{2}Pt_{2}O_{7} contains a broad anomaly
      centered at T^{*}=1.5  K. Our inelastic neutron scattering measurements reveal
      that this broad heat capacity anomaly sets the temperature scale for strong short
      range spin fluctuations. Below T_{N}=0.38  K, Er_{2}Pt_{2}O_{7} displays a gapped
      spin-wave spectrum with an intense, flat band of excitations at lower energy and
      a weak, diffusive band of excitations at higher energy. The flat band is well
      described by classical spin-wave calculations, but these calculations also
      predict sharp dispersive branches at higher energy, a striking discrepancy with
      the experimental data. This, in concert with the strong suppression of T_{N}, is
      attributable to enhanced quantum fluctuations due to phase competition between
      the Gamma_{7} and Gamma_{5} states that border each other within a classically
      predicted phase diagram.

PMID- 29219595
TI  - Topological Majorana Two-Channel Kondo Effect.
AB  - A one-dimensional time-reversal-invariant topological superconductor hosts a
      Majorana Kramers pair at each end, where time-reversal symmetry acts as a
      supersymmetry that flips local fermion parity. We examine the transport anomaly
      of such a superconductor, floating and tunnel-coupled to normal leads at its two
      ends. We demonstrate the realization of a topologically protected, channel
      symmetric, two-channel Kondo effect without fine-tuning. Whereas the nonlocal
      teleportation vanishes, a lead present at one end telecontrols the universal
      transport through the other end.

PMID- 29219596
TI  - Interference in the gg->h->gammagamma On-Shell Rate and the Higgs Boson Total
      Width.
AB  - We consider interference between the Higgs signal and QCD background in gg->h
      >gammagamma and its effect on the on-shell Higgs rate. The existence of sizable
      strong phases leads to destructive interference of about 2% of the on-shell cross
      section in the standard model. This effect can be enhanced by beyond the standard
      model physics. In particular, since it scales differently from the usual rates,
      the presence of interference allows indirect limits to be placed on the Higgs
      width in a novel way, using on-shell rate measurements. Our study motivates
      further QCD calculations to reduce uncertainties. We discuss possible width
      sensitive observables, both using total and differential rates and find that the
      HL-LHC can potentially indirectly constrain widths of order tens of MeV.

PMID- 29219592
TI  - Dark Matter Results from 54-Ton-Day Exposure of PandaX-II Experiment.
AB  - We report a new search for weakly interacting massive particles (WIMPs) using the
      combined low background data sets acquired in 2016 and 2017 from the PandaX-II
      experiment in China. The latest data set contains a new exposure of 77.1 live
      days, with the background reduced to a level of 0.8*10^{-3}  evt/kg/day, improved
      by a factor of 2.5 in comparison to the previous run in 2016. No excess events
      are found above the expected background. With a total exposure of 5.4*10^{4}  kg
      day, the most stringent upper limit on the spin-independent WIMP-nucleon cross
      section is set for a WIMP with mass larger than 100  GeV/c^{2}, with the lowest
      90% C.L. exclusion at 8.6*10^{-47}  cm^{2} at 40  GeV/c^{2}.

PMID- 29219597
TI  - Origin of Ultrastability in Vapor-Deposited Glasses.
AB  - Glass films created by vapor-depositing molecules onto a substrate can exhibit
      properties similar to those of ordinary glasses aged for thousands of years. It
      is believed that enhanced surface mobility is the mechanism that allows vapor
      deposition to create such exceptional glasses, but it is unclear how this effect
      is related to the final state of the film. Here we use molecular dynamics
      simulations to model vapor deposition and an efficient Monte Carlo algorithm to
      determine the deposition rate needed to create ultrastable glassy films. We
      obtain a scaling relation that quantitatively captures the efficiency gain of
      vapor deposition over bulk annealing, and demonstrates that surface relaxation
      plays the same role in the formation of vapor-deposited glasses as bulk
      relaxation does in ordinary glass formation.

PMID- 29219593
TI  - First Dark Matter Search Results from the XENON1T Experiment.
AB  - We report the first dark matter search results from XENON1T, a ~2000-kg-target
      mass dual-phase (liquid-gas) xenon time projection chamber in operation at the
      Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of
      this kind. The blinded search used 34.2 live days of data acquired between
      November 2016 and January 2017. Inside the (1042+/-12)-kg fiducial mass and in
      the [5,40]  keV_{nr} energy range of interest for weakly interacting massive
      particle (WIMP) dark matter searches, the electronic recoil background was
      (1.93+/-0.25)*10^{-4}  events/(kg*day*keV_{ee}), the lowest ever achieved in such
      a dark matter detector. A profile likelihood analysis shows that the data are
      consistent with the background-only hypothesis. We derive the most stringent
      exclusion limits on the spin-independent WIMP-nucleon interaction cross section
      for WIMP masses above 10  GeV/c^{2}, with a minimum of 7.7*10^{-47}  cm^{2} for
      35-GeV/c^{2} WIMPs at 90% C.L.

PMID- 29219599
TI  - Error Mitigation for Short-Depth Quantum Circuits.
AB  - Two schemes are presented that mitigate the effect of errors and decoherence in
      short-depth quantum circuits. The size of the circuits for which these techniques
      can be applied is limited by the rate at which the errors in the computation are
      introduced. Near-term applications of early quantum devices, such as quantum
      simulations, rely on accurate estimates of expectation values to become relevant.
      Decoherence and gate errors lead to wrong estimates of the expectation values of
      observables used to evaluate the noisy circuit. The two schemes we discuss are
      deliberately simple and do not require additional qubit resources, so to be as
      practically relevant in current experiments as possible. The first method,
      extrapolation to the zero noise limit, subsequently cancels powers of the noise
      perturbations by an application of Richardson's deferred approach to the limit.
      The second method cancels errors by resampling randomized circuits according to a
      quasiprobability distribution.

PMID- 29219598
TI  - Nucleation of Multiple Buckled Structures in Intertwined DNA Double Helices.
AB  - We study the statistical-mechanical properties of intertwined double-helical DNAs
      (DNA braids). In magnetic tweezers experiments, we find that torsionally stressed
      stretched braids supercoil via an abrupt buckling transition, which is associated
      with the nucleation of a braid end loop, and that the buckled braid is
      characterized by a proliferation of multiple domains. Differences between the
      mechanics of DNA braids and supercoiled single DNAs can be understood as an
      effect of the increased bulkiness in the structure of the former. The
      experimental results are in accord with the predictions of a statistical
      mechanical model.

PMID- 29219600
TI  - Stochastic Feshbach Projection for the Dynamics of Open Quantum Systems.
AB  - We present a stochastic projection formalism for the description of quantum
      dynamics in bosonic or spin environments. The Schrodinger equation in the
      coherent state representation with respect to the environmental degrees of
      freedom can be reformulated by employing the Feshbach partitioning technique for
      open quantum systems based on the introduction of suitable non-Hermitian
      projection operators. In this picture the reduced state of the system can be
      obtained as a stochastic average over pure state trajectories, for any
      temperature of the bath. The corresponding non-Markovian stochastic Schrodinger
      equations include a memory integral over the past states. In the case of harmonic
      environments and linear coupling the approach gives a new form of the established
      non-Markovian quantum state diffusion stochastic Schrodinger equation without
      functional derivatives. Utilizing spin coherent states, the evolution equation
      for spin environments resembles the bosonic case with, however, a non-Gaussian
      average for the reduced density operator.

PMID- 29219601
TI  - Probing the Fluctuations of Optical Properties in Time-Resolved Spectroscopy.
AB  - We show that, in optical pump-probe experiments on bulk samples, the statistical
      distribution of the intensity of ultrashort light pulses after interaction with a
      nonequilibrium complex material can be used to measure the time-dependent noise
      of the current in the system. We illustrate the general arguments for a
      photoexcited Peierls material. The transient noise spectroscopy allows us to
      measure to what extent electronic degrees of freedom dynamically obey the
      fluctuation-dissipation theorem, and how well they thermalize during the coherent
      lattice vibrations. The proposed statistical measurement developed here provides
      a new general framework to retrieve dynamical information on the excited
      distributions in nonequilibrium experiments, which could be extended to other
      degrees of freedom of magnetic or vibrational origin.

PMID- 29219602
TI  - Casimir-Lifshitz Torque Enhancement by Retardation and Intervening Dielectrics.
AB  - We investigate two effects that lead to a surprising increase in the calculated
      Casimir-Lifshitz torque between anisotropic, planar, semi-infinite slabs.
      Retardation effects, which account for the finite speed of light, are generally
      assumed to decrease the strength of Casimir-Lifshitz interactions. However, the
      nonretarded approximation underestimates the Casimir-Lifshitz torque at small
      separations by as much as an order of magnitude. Also, Casimir-Lifshitz forces
      are typically weakened with the insertion of an intervening dielectric. However,
      a dielectric medium can increase the short-range Casimir-Lifshitz torque by as
      much as a factor of 2. The combined effects of retardation and an intervening
      dielectric dramatically enhance the Casimir-Lifshitz torque in the experimentally
      accessible regime and should not be neglected in calculation or experimental
      design.

PMID- 29219603
TI  - Broadband Amplification of Low-Terahertz Signals Using Axis-Encircling Electrons
      in a Helically Corrugated Interaction Region.
AB  - Experimental results are presented of a broadband, high power, gyrotron traveling
      wave amplifier (gyro-TWA) operating in the (75-110)-GHz frequency band and based
      on a helically corrugated interaction region. The second harmonic cyclotron mode
      of a 55-keV, 1.5-A, axis-encircling electron beam is used to resonantly interact
      with a traveling TE_{21}-like eigenwave achieving broadband amplification. The
      gyro-TWA demonstrates a 3-dB gain bandwidth of at least 5.5 GHz in the
      experimental measurement with 9 GHz predicted for a wideband drive source with a
      measured unsaturated output power of 3.4 kW and gain of 36-38 dB. The approach
      may allow a gyro-TWA to operate at 1 THz.

PMID- 29219604
TI  - Phonon Sidebands in Monolayer Transition Metal Dichalcogenides.
AB  - Excitons dominate the optical properties of monolayer transition metal
      dichalcogenides (TMDs). Besides optically accessible bright exciton states, TMDs
      exhibit also a multitude of optically forbidden dark excitons. Here, we show that
      efficient exciton-phonon scattering couples bright and dark states and gives rise
      to an asymmetric excitonic line shape. The observed asymmetry can be traced back
      to phonon-induced sidebands that are accompanied by a polaron redshift. We
      present a joint theory-experiment study investigating the microscopic origin of
      these sidebands in different TMD materials taking into account intra- and
      intervalley scattering channels opened by optical and acoustic phonons. The
      gained insights contribute to a better understanding of the optical fingerprint
      of these technologically promising nanomaterials.

PMID- 29219605
TI  - Spin Resonance and Magnetic Order in an Unconventional Superconductor.
AB  - Unconventional superconductivity in many materials is believed to be mediated by
      magnetic fluctuations. It is an open question how magnetic order can emerge from
      a superconducting condensate and how it competes with the magnetic spin resonance
      in unconventional superconductors. Here we study a model d-wave superconductor
      that develops spin-density wave order, and find that the spin resonance is
      unaffected by the onset of static magnetic order. This result suggests a
      scenario, in which the resonance in Nd_{0.05}Ce_{0.95}CoIn_{5} is a longitudinal
      mode with fluctuating moments along the ordered magnetic moments.

PMID- 29219606
TI  - Achieving Optimal Quantum Acceleration of Frequency Estimation Using Adaptive
      Coherent Control.
AB  - Precision measurements of frequency are critical to accurate time keeping and are
      fundamentally limited by quantum measurement uncertainties. While for time
      independent quantum Hamiltonians the uncertainty of any parameter scales at best
      as 1/T, where T is the duration of the experiment, recent theoretical works have
      predicted that explicitly time-dependent Hamiltonians can yield a 1/T^{2} scaling
      of the uncertainty for an oscillation frequency. This quantum acceleration in
      precision requires coherent control, which is generally adaptive. We
      experimentally realize this quantum improvement in frequency sensitivity with
      superconducting circuits, using a single transmon qubit. With optimal control
      pulses, the theoretically ideal frequency precision scaling is reached for times
      shorter than the decoherence time. This result demonstrates a fundamental quantum
      advantage for frequency estimation.

PMID- 29219607
TI  - Passive Linearization of the Magnetic Bunch Compression Using Self-Induced
      Fields.
AB  - In linac-driven free-electron lasers, colliders, and energy recovery linacs, a
      common way to compress the electron bunch to kiloampere level is based upon the
      implementation of a magnetic dispersive element that converts particle energy
      deviation into a path-length difference. Nonlinearities of such a process are
      usually compensated by enabling a high harmonic rf structure properly tuned in
      amplitude and phase. This approach is however not straightforward, e.g., in C
      band and X-band linacs. In this Letter we demonstrate that the longitudinal self
      induced field excited by the electron beam itself is able to linearize the
      compression process without any use of high harmonic rf structure. The method is
      implemented at the FERMI linac, with the resulting high quality beam used to
      drive the seeded free-electron laser during user experiments.

PMID- 29219608
TI  - Operating Quantum States in Single Magnetic Molecules: Implementation of Grover's
      Quantum Algorithm.
AB  - Quantum algorithms use the principles of quantum mechanics, such as, for example,
      quantum superposition, in order to solve particular problems outperforming
      standard computation. They are developed for cryptography, searching,
      optimization, simulation, and solving large systems of linear equations. Here, we
      implement Grover's quantum algorithm, proposed to find an element in an unsorted
      list, using a single nuclear 3/2 spin carried by a Tb ion sitting in a single
      molecular magnet transistor. The coherent manipulation of this multilevel quantum
      system (qudit) is achieved by means of electric fields only. Grover's search
      algorithm is implemented by constructing a quantum database via a multilevel
      Hadamard gate. The Grover sequence then allows us to select each state. The
      presented method is of universal character and can be implemented in any
      multilevel quantum system with nonequal spaced energy levels, opening the way to
      novel quantum search algorithms.

PMID- 29219609
TI  - Spin Mode Switching at the Edge of a Quantum Hall System.
AB  - Quantum Hall states can be characterized by their chiral edge modes. Upon
      softening the edge potential, the edge has long been known to undergo spontaneous
      reconstruction driven by charging effects. In this Letter we demonstrate a
      qualitatively distinct phenomenon driven by exchange effects, in which the
      ordering of the edge modes at nu=3 switches abruptly as the edge potential is
      made softer, while the ordering in the bulk remains intact. We demonstrate that
      this phenomenon is robust, and has many verifiable experimental signatures in
      transport.

PMID- 29219610
TI  - Local Orthorhombicity in the Magnetic C_{4} Phase of the Hole-Doped Iron-Arsenide
      Superconductor Sr_{1-x}Na_{x}Fe_{2}As_{2}.
AB  - We report on temperature-dependent pair distribution function measurements of
      Sr_{1-x}Na_{x}Fe_{2}As_{2}, an iron-based superconductor system that contains a
      magnetic phase with reentrant tetragonal symmetry, known as the magnetic C_{4}
      phase. Quantitative refinements indicate that the instantaneous local structure
      in the C_{4} phase comprises fluctuating orthorhombic regions with a length scale
      of ~2  nm, despite the tetragonal symmetry of the average static structure.
      Additionally, local orthorhombic fluctuations exist on a similar length scale at
      temperatures well into the paramagnetic tetragonal phase. These results highlight
      the exceptionally large nematic susceptibility of iron-based superconductors and
      have significant implications for the magnetic C_{4} phase and the neighboring
      C_{2} and superconducting phases.

PMID- 29219611
TI  - Parallel Low-Loss Measurement of Multiple Atomic Qubits.
AB  - We demonstrate low-loss measurement of the hyperfine ground state of rubidium
      atoms by state dependent fluorescence detection in a dipole trap array of five
      sites. The presence of atoms and their internal states are minimally altered by
      utilizing circularly polarized probe light and a strictly controlled quantization
      axis. We achieve mean state detection fidelity of 97% without correcting for
      imperfect state preparation or background losses, and 98.7% when corrected. After
      state detection and correction for background losses, the probability of atom
      loss due to the state measurement is <2% and the initial hyperfine state is
      preserved with >98% probability.

PMID- 29219612
TI  - Nonprogression with avelumab treatment associated with gains in quality of life
      in metastatic Merkel cell carcinoma.
AB  - AIM: To assess the association between tumor response and health-related quality
      of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with
      the anti-PD-L1 avelumab. MATERIALS & METHODS: Phase II single-arm trial
      (NCT02155647) data of 88 patients were analyzed. Correlations between percentage
      reduction in tumor size and change from baseline in Functional Assessment of
      Cancer Therapy - General (FACT-G), FACT - Melanoma (FACT-M) and EuroQol-5
      Dimension scores were calculated. HRQoL and utility by tumor response (per the
      Response Evaluation Criteria In Solid Tumors version 1.1) was estimated. RESULTS:
      Tumor shrinkage correlated positively with patients' change from baseline in the
      FACT-M total (0.364 [95% CI: 0.050-0.607]) and subscale scores. Differences in
      HRQoL and utility between nonprogressive disease and progressive disease were
      clinically relevant. CONCLUSION: In patients with metastatic Merkel cell
      carcinoma, nonprogression during treatment with avelumab correlated with gains in
      HRQoL.

PMID- 29219613
TI  - Isolation and characterization of a bacterium able to degrade high concentrations
      of iprodione.
AB  - A bacterial strain CQH-1 capable of mineralizing iprodione was isolated and
      characterized. On the basis of its morphological, physiological, and biochemical
      characteristics combined with phylogenetic analysis of its 16S rRNA gene
      sequence, strain CQH-1 was identified as a Microbacterium sp. CQH-1. It was able
      to use iprodione and 3,5-dichloroaniline as the sole source of carbon and energy
      for its growth. It completely degraded 100 mg.L-1 iprodione within 96 h at 30 
      degrees C. During the degradation of iprodione by strain CQH-1, 2 compounds were
      detected in GC-MS analysis and were recognized as N-(3,5-dichlorophenyl)-2,4
      dioxoimidazolidine and 3,5-dichloroaniline. So, the biodegradation pathway of
      iprodione by strain CQH-1 was proposed. This is the first report of an iprodione
      mineralizing strain from the genus Microbacterium, and strain CQH-1 might be a
      promising candidate for application in the bioremediation of iprodione
      contaminated environments.

PMID- 29219614
TI  - Osteoblast-like cells in human cancers: new cell type and reliable markers for
      bone metastasis.

PMID- 29219615
TI  - Therapy sequencing strategies in multiple myeloma: who, what and why?

PMID- 29219616
TI  - Next-Generation Sequencing Approach to Non-Small Cell Lung Carcinoma Yields More
      Actionable Alterations.
AB  - CONTEXT: - Different testing algorithms and platforms for EGFR mutations and ALK
      rearrangements in advanced-stage lung adenocarcinoma exist. The multistep
      approach with single-gene assays has been challenged by more efficient next
      generation sequencing (NGS) of a large number of gene alterations. The main
      criticism of the NGS approach is the detection of genomic alterations of
      uncertain significance. OBJECTIVE: - To determine the best testing algorithm for
      patients with lung cancer in our clinical practice. DESIGN: - Two testing
      approaches for metastatic lung adenocarcinoma were offered between 2012-2015. One
      approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing
      for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK,
      ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the
      8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel. RESULTS: - Of
      1200 non-small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and
      NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large
      cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer
      Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29
      adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%)
      in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of
      29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2
      LCNECs showed investigational genomic alterations. CONCLUSIONS: - The NGS
      approach would result in the identification of a significant number of actionable
      gene alterations, increasing the therapeutic options for patients with advanced
      NSCLCs.

PMID- 29219618
TI  - Global health watch 5: an alternative world health report.

PMID- 29219617
TI  - Exploring Multiphoton Microscopy as a Novel Tool to Differentiate Chromophobe
      Renal Cell Carcinoma From Oncocytoma in Fixed Tissue Sections.
AB  - CONTEXT: - Distinguishing chromophobe renal cell carcinoma (chRCC), especially in
      the presence of eosinophilic cytoplasm, from oncocytoma on hematoxylin-eosin can
      be difficult and often requires time-consuming ancillary procedures that
      ultimately may not be informative. OBJECTIVE: - To explore the potential of
      multiphoton microscopy (MPM) as an alternative and rapid diagnostic tool in
      differentiating oncocytoma from chRCC at subcellular resolution without tissue
      processing. DESIGN: - Unstained, deparaffinized tissue sections from 27 tumors
      (oncocytoma [n = 12], chRCC [n = 12], eosinophilic variant of chRCC [n = 1], and
      atypical oncocytic renal neoplasm [n = 2]) were imaged with MPM. Morphologic
      evaluation and automated quantitative morphometric analysis were conducted to
      distinguish between chRCC and oncocytoma. RESULTS: - The typical cases of
      oncocytomas (12 of 12) and chRCC (12 of 12) could be readily differentiated on
      MPM based on the morphologic features similar to hematoxylin-eosin. The most
      striking MPM signature of both of the tumors was the presence of autofluorescent
      intracytoplasmic granules, which are not seen on hematoxylin-eosin-stained
      slides. Although we saw these granules in both types of tumors, they appeared
      distinct, based on their size, shape, cytoplasmic distribution, and
      autofluorescence wavelengths, and were valuable in arriving at a definitive
      diagnosis. For oncocytomas and chRCC, high diagnostic accuracies of 100% and
      83.3% were achieved on blinded MPM and morphometric analysis, respectively.
      CONCLUSIONS: - To the best of our knowledge, this is the first demonstration of
      MPM to distinguish chRCC from oncocytoma in fixed tissues. Our study was limited
      by small sample size and only a few variants of oncocytic tumors. Prospective
      studies are warranted to assess the utility of MPM as a diagnostic aid in
      oncocytic renal tumors.

PMID- 29219620
TI  - A common humoral background of intraocular and arterial blood pressure
      dysregulation.
AB  - BACKGROUND: It has been postulated that intraocular pressure, an important
      glaucoma risk factor, correlates positively with arterial blood pressure (blood
      pressure). However, results of experimental and clinical studies are often
      contradictory. It is hypothesized that, in some hypertensive patients,
      disturbances in intraocular pressure regulation may depend on biological effects
      of blood borne hormones underlying a particular type of hypertension, rather than
      on blood pressure level itself. REVIEW: This review compares the effects of
      hormones on blood pressure and intraocular pressure, in order to identify a
      hormonal profile of hypertensive patients with an increased risk of intraocular
      pressure surge. The PUBMED database was searched to identify pre-clinical and
      clinical studies investigating the role of angiotensin II, vasopressin,
      adrenaline, noradrenaline, prostaglandins, and gaseous transmitters in the
      regulation of blood pressure and intraocular pressure. RESULTS: Studies included
      in the review suggest that intraocular and blood pressures often follow a
      different pattern of response to the same hormone. For example, vasopressin
      increases blood pressure, but decreases intraocular pressure. In contrast, high
      level of nitric oxide decreases blood pressure, but increases intraocular
      pressure. CONCLUSIONS: Arterial hypertension is associated with altered levels of
      blood borne hormones. Contradicting results of studies on the relationship
      between arterial hypertension and intraocular pressure might be partially
      explained by diverse effects of hormones on arterial and intraocular pressures.
      Further studies are needed to evaluate if hormonal profiling may help to identify
      glaucoma-prone patients.

PMID- 29219619
TI  - Prenatal and Early Life Fructose, Fructose-Containing Beverages, and Midchildhood
      Asthma.
AB  - RATIONALE: Cross-sectional studies have linked intake of high-fructose corn syrup
      sweetened beverages with asthma in schoolchildren. OBJECTIVES: To examine
      associations of maternal prenatal and early childhood intake of sugar-sweetened
      beverages and fructose with current asthma in midchildhood (median age, 7.7 yr).
      METHODS: We assessed maternal pregnancy (first- and second-trimester average) and
      child (median age, 3.3 yr) intake of sugar-sweetened beverages and total fructose
      using food frequency questionnaires in 1,068 mother-child pairs from Project
      Viva, a prospective prebirth cohort. In a multivariable analysis, we examined
      associations of quartiles of maternal and child sugar-sweetened beverage, juice,
      and total fructose intake with child current asthma in midchildhood, assessed by
      questionnaire as ever having doctor-diagnosed asthma plus taking asthma
      medications or reporting wheezing in the past 12 months. RESULTS: Higher maternal
      pregnancy sugar-sweetened beverage consumption (mean, 0.6 servings/d; range, 0-5)
      was associated with younger maternal age, nonwhite race/ethnicity, lower
      education and income, and higher prepregnancy body mass index. Adjusting for
      prepregnancy body mass index and other covariates, comparing quartile 4 with
      quartile 1, higher maternal pregnancy intake of sugar-sweetened beverages (odds
      ratio, 1.70; 95% confidence interval, 1.08-2.67) and total fructose (odds ratio,
      1.58; 95% confidence interval, 0.98-2.53) were associated with greater odds of
      midchildhood current asthma (prevalence, 19%). Higher early childhood fructose
      intake (quartile 4 vs. quartile 1) was also associated with midchildhood current
      asthma in models adjusted for maternal sugar-sweetened beverages (odds ratio,
      1.79; 95% confidence interval, 1.07-2.97) and after additional adjustment for
      midchildhood body mass index z-score (odds ratio, 1.77; 95% confidence interval,
      1.06-2.95). CONCLUSIONS: Higher sugar-sweetened beverage and fructose intake
      during pregnancy and in early childhood was associated with childhood asthma
      development independent of adiposity.

PMID- 29219621
TI  - Clinical trial transparency update: an assessment of the disclosure of results of
      company-sponsored trials associated with new medicines approved in Europe in
      2014.
AB  - BACKGROUND: The objective of this study was to assess the timely disclosure of
      results of company-sponsored clinical trials related to all new medicines
      approved by the European Medicines Agency (EMA) during 2014. This is the final
      extension of three previously reported studies of trials related to all new
      medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The
      original study found that over a three-year period over three-quarters of all
      trials were disclosed within 12 months and almost 90% were disclosed by the end
      of the study (31 January 2013). The extension studies (2012 and 2013 approvals)
      both showed an improvement in results disclosure within 12 months to 90%, and an
      overall disclosure rate of 92% and 93% respectively by the end of the studies.
      METHODS: The methodology used was exactly as previously reported. Various
      publicly available information sources were searched for both clinical trial
      registration and disclosure of results. All completed company-sponsored trials
      related to each new medicine approved for marketing by the EMA in 2014, carried
      out in patients and recorded on a clinical trials registry and/or included in an
      EMA European Public Assessment Report (EPAR), were included. Information sources
      were searched between 1 May and 31 July 2016. OUTCOME MEASURES AND RESULTS: The
      main outcome measure was the proportion of trials for which results had been
      disclosed on a registry or in the scientific literature either within 12 months
      of the later of either first regulatory approval or trial completion, or by 31
      July 2016 (end of survey). Of the completed trials associated with 32 new
      medicines licensed to 22 different companies in 2014, results of 93% (505/542)
      had been disclosed within 12 months, and results of 96% (518/542) had been
      disclosed by 31 July 2016. CONCLUSIONS: The disclosure rate within 12 months of
      93% suggests that industry is continuing to achieve disclosure in a timely
      manner. The overall disclosure rate at study end of 96% indicates that the
      improvement in transparency amongst company-sponsored trials has been maintained
      in the trials associated with new medicines approved in 2014.

PMID- 29219623
TI  - Usual normalization strategies for gene expression studies impair the detection
      and analysis of circadian patterns.
AB  - Recent studies have shown that transcriptomes from different tissues present
      circadian oscillations. Therefore, the endogenous variation of total RNA should
      be considered as a potential bias in circadian studies of gene expression.
      However, normalization strategies generally include the equalization of total RNA
      concentration between samples prior to cDNA synthesis. Moreover, endogenous
      housekeeping genes (HKGs) frequently used for data normalization may exhibit
      circadian variation and distort experimental results if not detected or
      considered. In this study, we controlled experimental conditions from the amount
      of initial brain tissue samples through extraction steps, cDNA synthesis, and
      quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total
      RNA concentration. We also identified that the normalization of the RNA's yield
      affected the rhythmic profiles of different genes, including Per1-2 and Bmal1.
      Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented
      rhythmic variations not detected by geNorm algorithm. In addition, the analysis
      of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction
      suggests that the yield was affected by total RNA concentration, which may impact
      circadian studies of small RNAs. The results indicate that the approach of tissue
      normalization without total RNA equalization prior to cDNA synthesis can avoid
      bias from endogenous broad variations in transcript levels. Also, the circadian
      analysis of 2-Cycle threshold (Ct) data, without HKGs, may be an alternative for
      chronobiological studies under controlled experimental conditions.

PMID- 29219624
TI  - Can we predict the response to therapy in soft tissue sarcoma?

PMID- 29219626
TI  - Eveningness is associated with skipping breakfast and poor nutritional intake in
      Brazilian undergraduate students.
AB  - Some studies have proposed that self-reported eveningness, which reflects the
      preference of performing activities in the evening, may harm nutritional health
      and influence the eating behavior and nutritional status of individuals. However,
      the relationship between these variables (eveningness and nutritional status) and
      the consumption of breakfast, which is currently considered a marker of health,
      has been insufficiently explored by studies. The aim of this study was to
      investigate, in undergraduate students, the association between diurnal
      preference, being overweight, and food consumption (with special focus on
      breakfast). The study included 721 undergraduate students from a Brazilian public
      university. Dietary intake was assessed by 24-hour food recall, and the usual
      time for breakfast was identified. Body weight, height, and waist circumference
      were measured by trained researchers. Diurnal preference was determined by the
      Horne and Ostberg questionnaire validated for the Brazilian population, and the
      participants were classified into three categories: evening (coefficient: 16-41),
      intermediate type (coefficient: 42-58) or morning type (coefficient: 59-86). The
      prevalence of skipping breakfast was higher among the evening types (p = 0.02),
      when compared with morning and intermediate types. A negative association between
      the diurnal preference coefficient and total caloric (coefficient -0.25, p =
      0.007, r2 adjusted = 0.12), carbohydrate (coefficient -0.19, p = -0.04, r2
      adjusted = 0.04) and lipid intake (coefficient -0.18, p = 0.04, r2 adjusted =
      0.05) was also found in the breakfast skippers but not in breakfast eaters. In
      other words, breakfast skippers with diurnal preference values indicative of
      eveningness consumed more calories, carbohydrates and fats. Evening types
      presented significant odds of skipping breakfast (OR = 1.7, CI = 1.1-2.9, p =
      0.02) when compared with morning and intermediate chronotypes. We conclude that
      eveningness is associated with skipping breakfast and a higher consumption of
      calories, carbohydrates and fats in breakfast skippers. These eating behaviors
      may predispose these individuals to being overweight.

PMID- 29219625
TI  - Utility of point shear wave elastography in characterisation of focal liver
      lesions.
AB  - BACKGROUND: The present study aimed at evaluation of the usefulness of point
      shear wave elastography (pSWE) in characterization of FLL(s) by quantifying their
      stiffness. METHODS: In total, 197 patients (mean age was 56.57 years) with FLL(s)
      on conventional ultrasound were included. Final diagnoses, confirmed by imaging
      and/or biopsy whenever possible, included hepatocellular carcinoma (HCC) (n =
      143), metastasis (n = 36), hemangioma (n = 16), and focal nodular hyperplasia (n
      = 2). Stiffness evaluation was performed by pSWE. Stiffness ratio (lesion to
      background liver) was calculated. ROC analysis was performed to evaluate the
      diagnostic accuracy of the stiffness value and stiffness ratio and to extract the
      optimal cutoff values for characterisation of FLL(s). RESULTS: HCC was
      significantly softer than its surrounding liver parenchyma [5.43 (3.03) vs. 17.05
      (8.53) kPa, p <0.001]. However, the stiffness values for the other examined FLLs
      were comparable to their surrounding liver parenchyma. No significant difference
      was detected across different types of metastases or between metastases and
      surrounding liver (p>0.05). Stiffness ratio was superior to stiffness value in
      discrimination of HCC from metastasis (AUROC, 0.91 vs. 0.51 respectively).
      CONCLUSION: pSWE could provide a complementary information about FLLs especially
      in differentiation between HCCs from metastases.

PMID- 29219627
TI  - Non-oncotic properties of albumin. A multidisciplinary vision about the
      implications for critically ill patients.
AB  - INTRODUCTION: Effective resuscitation with human albumin solutions is achieved
      with less fluid than with crystalloid solutions. However, the role of albumin in
      today's critical care unit is also linked to its multiple pharmacological
      effects. Areas covered: The potential clinical benefits of albumin in select
      populations of critically ill patients like sepsis seem related to
      immunomodulatory and anti-inflammatory effects, antibiotic transportation and
      endothelial stabilization. Albumin transports many drugs used in critically ill
      patients. Such binding to albumin is frequently lessened in critically ill
      patients with hypoalbuminemia. These changes could result in sub-optimal
      treatment. Albumin has immunomodulatory capacity by binding several bacterial
      products. Albumin also influences vascular integrity, contributing to the
      maintenance of the normal capillary permeability. Moreover, the albumin molecule
      encompasses several antioxidant properties, thereby significantly reducing re
      oxygenation injury, which is especially important in sepsis. In fact, most
      studies of albumin administration are a combination of a degree of resuscitation
      with a degree of maintenance or supplementation of albumin. Expert commentary:
      The potential clinical benefits of the use of albumin in selected critically ill
      patients such as sepsis seem related to its immunomodulatory and anti
      inflammatory effects, antioxidant properties, antibiotic transportation and
      endothelial stabilization. Additional studies are warranted to further elucidate
      the underlying physiologic and molecular rationale.

PMID- 29219629
TI  - Pharmacotherapy options for managing chemotherapy-induced peripheral
      neurotoxicity.
AB  - INTRODUCTION: Prevention and treatment of chemotherapy-induced peripheral
      neurotoxicity (CIPN) are clinically-relevant unmet needs. Despite extensive
      efforts at the preclinical and clinical levels, no effective pharmacological
      interventions are available, and this unsatisfactory situation reflects a
      combination of methodological issues and a lack of effectiveness of the tested
      drugs. Areas covered: This non-systematic, but unbiased review is based on
      published papers available in PubMed and screened using the broad search string
      [chemotherapy (and) neuropathy (and) treatment] to analyze the reported data.
      Subsequently, the same search was performed in ClinicalTrials.gov to assess the
      trend of new clinical studies. Expert opinion: From the analysis of the most
      recently published clinical studies and of the ongoing registered trials it seems
      that drug-based treatment attempts are being overwhelmed by non-pharmacological
      studies, in most cases based on weak supporting hypothesis. Among the possible
      strategies important to restore a prominent role for drug-based clinical trials,
      increased knowledge on CIPN pathophysiology, more effective translation of
      preclinical results into clinical setting, improvement in CIPN assessment and the
      identification of subjects at high-risk for more severe CIPN are important areas
      to concentrate investigational efforts.

PMID- 29219628
TI  - Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of
      haloperidol: in vitro characterization, ex vivo permeation and in vivo
      biodistribution studies.
AB  - Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally
      administered, it suffers from low bioavailability due to hepatic first pass
      metabolism. This study aimed at developing Hal-loaded penetration enhancer
      containing spanlastics (PECSs) to increase transdermal permeation of Hal with
      sustained release. PECSs were successfully prepared using ethanol injection
      method showing reasonable values of percentage entrapment efficiency, particle
      size, polydispersity index and zeta potential. The statistical analysis of the ex
      vivo permeation parameters led to the choice of F1L - made of Span(r) 60 and
      Tween(r) 80 at the weight ratio of 4:1 along with 1% w/v Labrasol(r) - as the
      selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of
      HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained
      its physical and chemical stability for one month in the refrigerator. The
      radiolabeling of SF showed a maximum yield by mixing of 100 ul of diluted formula
      with 50 ul saline having 200 MBq of 99mTc and containing 13.6 mg of reducing
      agent (NaBH4) and volume completed to 300 ul by saline at pH 10 for 10 min as
      reaction time. The biodistribution study showed that the transdermal 99mTc-SF
      hydrogel exhibited a more sustained release pattern and longer circulation
      duration with pulsatile behavior in the blood and higher brain levels than the
      oral 99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a
      promising sustained release formula for Hal maintenance therapy with reduced dose
      size and less frequent administration than oral formula.

PMID- 29219589
TI  - Observation of D^{0} Meson Decays to pi^{+}pi^{-}MU^{+}MU^{-} and K^{+}K^{
      }MU^{+}MU^{-} Final States.
AB  - The first observation of the D^{0}->pi^{+}pi^{-}MU^{+}MU^{-} and D^{0}->K^{+}K^{
      }MU^{+}MU^{-} decays is reported using a sample of proton-proton collisions
      collected by LHCb at a center-of-mass energy of 8 TeV, and corresponding to 2 
      fb^{-1} of integrated luminosity. The corresponding branching fractions are
      measured using as normalization the decay D^{0}->K^{-}pi^{+}[MU^{+}MU^{
      }]_{rho^{0}/omega}, where the two muons are consistent with coming from the decay
      of a rho^{0} or omega meson. The results are B(D^{0}->pi^{+}pi^{-}MU^{+}MU^{
      })=(9.64+/-0.48+/-0.51+/-0.97)*10^{-7} and B(D^{0}->K^{+}K^{-}MU^{+}MU^{
      })=(1.54+/-0.27+/-0.09+/-0.16)*10^{-7}, where the uncertainties are statistical,
      systematic, and due to the limited knowledge of the normalization branching
      fraction. The dependence of the branching fraction on the dimuon mass is also
      investigated.

PMID- 29219630
TI  - Fewer adverse effects with a modified two-bag acetylcysteine protocol in
      paracetamol overdose.
AB  - OBJECTIVE: Acetylcysteine (NAC), an effective antidote for paracetamol poisoning,
      is commonly associated with adverse reactions. This has been postulated to be
      related to the rapid initial infusion rate (150 mg/kg over 1 h) of the
      traditional three-bag protocol. We hypothesized that a slower rate would result
      in fewer adverse reactions. Our institution in Western Sydney moved to a modified
      two-bag protocol in February 2015 - first bag: 200 mg/kg over 4 h (50 mg/kg/h)
      and second bag: (100 mg/kg over 16 h). METHODS: Data was extracted from our
      database on paracetamol overdoses treated with NAC from August 2010 to September
      2016. We compared adverse reactions in patients receiving the modified two-bag
      protocol with a historical control (traditional three-bag regimen with initial
      bolus of 150 mg/kg/h). RESULTS: Over the study period 1011 paracetamol poisonings
      presented to our toxicology service, of which 476 required NAC (three-bag = 313,
      two-bag = 163). Demographic characteristics of the two groups were similar. Fewer
      anaphylactoid reactions (itch, rash, and swelling) occurred using the two-bag
      regimen (14% versus 5%, p = .002), a relative reduction of 66%. Similarly, there
      were fewer prescriptions of anti-allergy medications in the two-bag group (11%
      versus 4%, p = .01). There was no difference in incidence of hepatotoxicity.
      CONCLUSIONS: Adverse reactions to NAC were less common with the two-bag regimen.
      These results add to the accumulating evidence that reducing the initial NAC
      infusion rate reduces the risk of adverse reactions.

PMID- 29219631
TI  - Tourette syndrome and other chronic tic disorders: an update on clinical
      management.
AB  - INTRODUCTION: The management of Tourette syndrome (TS) and other chronic tic
      disorders occurs in multiple stages and begins with comprehensive assessment and
      complex psychoeducation. Behavioral and pharmacological interventions (second
      stage) are needed when tics cause physical or psychosocial impairment. Deep brain
      stimulation surgery or experimental therapies represent the third stage. Areas
      covered: Discussed are recent advances in assessment and therapy of chronic tic
      disorders, encompassing the three stages of intervention, with the addition of
      experimental, non-invasive brain stimulation strategies. A PubMed search was
      performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment',
      'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain
      stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial
      current stimulation'. More than 300 peer-reviewed articles were evaluated. The
      studies discussed have been selected on the basis of novelty and impact. Expert
      commentary: Comprehensive assessment of tic disorders and psychoeducation are
      crucial to a correct active management approach. Behavioral treatments represent
      first line of active interventions, with increasing potential offered by
      telehealth. Antipsychotics and alpha agonists remain first line pharmacological
      interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain
      stimulation is a potential option for medically refractory, severely disabled
      patients with tics, but age and target selection require further investigation.

PMID- 29219632
TI  - Budd Chiari syndrome associated with AL amyloidosis: a coagulation paradox.

PMID- 29219633
TI  - Brain activity during phonation in healthy female singers with supraglottic
      compression: an fMRI pilot study.
AB  - This pilot study evaluated the usability of functional magnetic resonance imaging
      (fMRI) to detect brain activation during phonation in healthy female singers with
      supraglottic compression. Four healthy female classical singers (mean age: 26
      years) participated in the study. All subjects had normal vocal folds and vocal
      characteristics and showed supraglottic compression. The fMRI experiment was
      carried out using a block design paradigm. Brain activation during phonation and
      exhalation was analyzed using Brain Voyager software (Brain Innovation B.V.,
      Maastricht, The Netherlands). An fMRI data analysis showed a significant effect
      of phonation control in the bilateral pre/postcentral gyrus, and in the frontal,
      cingulate, superior and middle temporal gyrus, as well as in the parietal lobe,
      insula, lingual gyrus, cerebellum, thalamus and brainstem. These activation areas
      are consistent with previous reports using other fMRI protocols. In addition, a
      significant effect of phonation compared to exhalation control was found in the
      bilateral superior temporal gyrus, and the pre/postcentral gyrus. This fMRI pilot
      study allowed to detect a normal pattern of brain activity during phonation in
      healthy female singers with supraglottic compression using the proposed protocol.
      However, the pilot study detected problems with the experimental
      material/procedures that would necessitate refining the fMRI protocol. The
      phonation tasks were not capable to show brain activation difference between high
      pitched and comfortable phonation. Further fMRI studies manipulating vocal
      parameters during phonation of the vowels /a/ and /i/ may elicit more distinctive
      hemodynamic response (HDR) activity patterns relative to voice modulation.

PMID- 29219635
TI  - Hashtag #TBI: A content and network data analysis of tweets about Traumatic Brain
      Injury.
AB  - OBJECTIVE: The aims of this study were to: (a) determine how Twitter is used by
      people with traumatic brain injury (TBI) and TBI organisations, (b) analyse the
      Twitter networks and content of tweets tagged with TBI-related hashtags, and (c)
      identify any challenges people with TBI encounter in using Twitter. RESEARCH
      DESIGN: Mixed methods in a Twitter hashtag study. METHODS: Mixed methods in a
      Twitter hashtag study. Tweets tagged with TBI-related hashtags were harvested
      from the Twitter website over a one-month period in 2016 and analysed
      qualitatively and quantitatively. RESULTS: The sample of 29,199 tweets included
      tweets sent by 893 @users, 219 of whom had a brain injury. Twitter was used to:
      (a) discuss health issues, (b) raise awareness of TBI, (c) talk about life after
      TBI, (d) talk about sport and concussion, and (e) communicate inspirational
      messages. CONCLUSIONS: Twitter is an important platform for research and
      knowledge translation on TBI, and for hearing the voices of people with TBI as
      they express their personal views and stories of living with TBI and become more
      visible and influential in Twitter communities. TBI clinicians could use these
      narratives of people with TBI in Twitter to develop more effective and personally
      meaningful rehabilitation goals.

PMID- 29219634
TI  - Using molecular imaging to understand early schizophrenia-related psychosis
      neurochemistry: a review of human studies.
AB  - Schizophrenia is a chronic psychiatric disorder generally preceded by a so-called
      prodromal phase, which is characterized by attenuated psychotic symptoms.
      Advances in clinical research have enabled prospective identification of those
      individuals who are at clinical high risk (CHR) for psychosis, with the power to
      predict psychosis onset within the near future. Changes in several brain
      neurochemical systems and molecular mechanisms are implicated in the
      pathophysiology of schizophrenia and the psychosis spectrum, including the
      dopaminergic, gamma-aminobutyric acid (GABA)-ergic, glutamatergic,
      endocannabinoid, and immunologic (i.e. glial activation) system and other
      promising future directions such as synaptic density, which are possible to
      quantify in vivo using positron emission tomography (PET). This paper aims to
      review in vivo PET studies in the mentioned systems in the early course of
      psychosis (i.e. CHR and first-episode psychosis (FEP)). The results of reviewed
      studies are promising; however, the current understanding of the underlying
      pathology of psychosis is still limited. Importantly, promising efforts involve
      the development of novel PET radiotracers targeting systems with growing interest
      in schizophrenia, like the nociceptive system and synaptic density.

PMID- 29219636
TI  - Physiological effects of brominated flame retardants on NC/Nga mice.
AB  - PURPOSE: Brominated flame retardants (BFRs) are used as an additive or reactive
      components in various materials. Regarding their health concerns, their
      immunotoxicity have not been clarified yet. MATERIALS AND METHODS: In the current
      study, we examined the effects of systemic exposure to two types of BFRs, DE71
      and DE79, on pathophysiologic traits of murine atopic dermatitis (AD). Male
      NC/Nga mice were repeatedly injected intraperitoneally with DE71 and DE79 and/or
      mite allergen (Dermatophagoides pteronyssinus: Dp) into their right ears.
      Thereafter, clinical scores, macroscopic findings of inflammatory foci, and Ig
      values in serum were examined. RESULTS: Both DEs significantly aggravated
      clinical scores induced by mite allergen including skin dryness and edema. Total
      IgE titer was significantly greater in the Dp + DE79 group than in the Dp group.
      CONCLUSIONS: Taken together, exposure to BFRs can exacerbate AD-like skin lesions
      related to mite allergen in mice. The accentuating effects may be mediated, at
      least in part, through hyperproduction of IgE.

PMID- 29219637
TI  - First Cases of Hb Agrinio Described in Patients from the Republic of Macedonia.
AB  - Previous molecular analyses of alpha-thalassemia (alpha-thal) in the Republic of
      Macedonia have identified the following genetic defects: -alpha3.7 (rightward), 
      (alpha)20.5 and - -MED I deletions and Hb Icaria [alpha142, Term->Lys (alpha2),
      HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (alpha2), HBA2:
      c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani
      population in the Republic of Macedonia, homozygotes for the alpha2-globin gene
      variant Hb Agrinio [alpha29(B10)Leu->Pro; HBA2: c.89T>C]. To date, Hb Agrinio has
      been described only in individuals of Greek, Cypriot and Spanish origin. Both of
      our patients had early presentation of the disease (3.5 years and 2 months,
      respectively) with frequent blood transfusions from early infancy. They have a
      severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb)
      levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2: c.89T>C mutation
      results in an alpha+ allele, the severe phenotype of the homozygotes is due to
      the production of hyperunstable alpha chains that undergo post translational
      precipitation. This leads to a greater degree of red cell damage and hemolytic
      anemia. The detection of Hb Agrinio in two unrelated families of Romani ethnic
      origin, may suggest it is a founder mutation in this population living in the
      Republic of Macedonia. Considering the severity of the clinical presentation of
      the homozygotes or compound heterozygotes for this rare Hb variant, a targeted
      molecular screening for Hb Agrinio mutation carriers should be considered in all
      patients of Romani ethnic origin with manifested microcytosis.

PMID- 29219639
TI  - Correction to: Yuki Harada et al., CINCA syndrome with surgical intervention for
      valgus deformity and flexion contracture of the knee joint: A case report.

PMID- 29219638
TI  - Clinical efficacy, radiographic, and safety results of golimumab monotherapy in
      Japanese patients with active rheumatoid arthritis despite prior therapy with
      disease-modifying antirheumatic drugs: Final results of the GO-MONO trial through
      week 120.
AB  - OBJECTIVE: Evaluate the safety and efficacy of golimumab through week 120 in
      Japanese patients with active rheumatoid arthritis (RA) previously treated with
      DMARDs. METHODS: Japanese patients with active RA despite prior DMARDs were
      randomized to placebo (Group 1, n = 105), golimumab 50 mg (Group 2, n = 101), or
      golimumab 100 mg (Group 3, n = 102). At week 16, Group 1 patients crossed over to
      golimumab 50mg; after week 52, a one-time golimumab dose reduction from 100 to 50
      mg was permitted. Assessments included ACR20/50/70 responses and good/moderate
      DAS28-ESR responses. Radiographic progression was assessed with the van der
      Heijde-modified Sharp (vdH-S) score. Safety and efficacy were assessed through
      week 120. RESULTS: ACR20 response rates at week 52 in Group 1, Group 2, and Group
      3 were 70.6%, 71.4%, and 81.9%, respectively, and maintained through week 104
      (87.2%, 85.1%, 88.9%, respectively) and week 120 (86.1%, 87.0%, 89.5%,
      respectively). Similar trends were observed for ACR50, ACR 70, and DAS28-ESR.
      Median change in total vdH-S at weeks 52, 104, and 120 ranged from 0.0 to 1.5
      across treatment groups. Through week 120, 93.8%/97.1% had an AE with golimumab
      50 mg/100 mg, respectively, and 19.7%/11.8% had an SAE. Infections were the most
      common AE. CONCLUSION: Clinical response to golimumab 50 mg and 100 mg was
      maintained over 2 years in Japanese patients with active RA despite prior DMARDs.

PMID- 29219640
TI  - Treatment of Parkinson's disease.
AB  - Preview Although the early symptoms of Parkinson's disease can be ameliorated,
      the illness is relentlessly progressive. Studies have therefore been conducted in
      hopes of finding therapy to delay its disabling course. In this article, Dr
      Ahlskog examines recent proposals and their application in cases of early and
      advancing disease.

PMID- 29219641
TI  - Osteoporosis.
AB  - Preview A reduction in bone mass seems to be inevitable with aging, but
      osteoporotic fractures need not be. As Dr Watts explains, recent advances in
      diagnosis and treatment of osteoporosis have been significant. Patients at
      increased risk of fracture can be identified with use of bone-density
      measurements, and proven and experimental treatment methods are available to
      prevent bone loss and increase bone mass.

PMID- 29219642
TI  - The dementia syndromes.
AB  - Preview Dementia is one of the most devastating illnesses that affect the
      elderly. The progressive decline in memory, judgment, intellectual function, and
      adaptive ability places an immense burden on families, healthcare providers, and
      communities. Because advancing age is the leading risk factor for most types of
      dementia, the prevalence of this tragic disorder will increase as the population
      ages. How can primary care physicians help?

PMID- 29219643
TI  - Current options in gallstone management.
AB  - Preview Should surgery to remove gallstones be deferred until symptoms occur?
      When should therapy with oral bile acids, lithotripsy, or methyl tert-butyl ether
      be considered? How should nonspecific dyspeptic symptoms in a patient with
      cholelithiasis be managed? Dr Marshall discusses these and other questions and
      controversies.

PMID- 29219644
TI  - Tick-borne infections.
AB  - Preview Is it because people are traveling more often or to more remote locations
      or because exposure to ticks is becoming more common? Whatever the reason,
      diseases spread by tick bites are being reported more often than in the past.
      Some of these, such as Rocky Mountain spotted fever and ehrlichiosis, can have
      very severe, even fatal, consequences. Dr Middleton describes findings that
      suggest tick-borne disease and summarizes effective treatment and prevention
      methods.

PMID- 29219645
TI  - Hoarseness.
AB  - Preview A patient's complaint of hoarseness cannot be taken lightly. Although the
      cause may simply be a limited illness, a life- threatening disease could be the
      underlying problem. The authors review the necessary observations in history
      taking and physical examination of the hoarse patient; these cover a wide range
      of behaviors, conditions, and situations. The goal is to provide an accurate and
      quick diagnosis so that proper treatment can begin at once.

PMID- 29219646
TI  - Diabetic gastroparesis.
AB  - Preview As many as 30% of patients with long-standing diabetes mellitus may have
      symptoms of gastroparesis, and others are found to have the condition despite
      being asymptomatic. When should diabetic gastroparesis be suspected, and which
      are the best tests for detecting it? What factors can exacerbate it? Drs Clark
      and Nowak address these questions and discuss the therapeutic value of dietary
      modification, pro- kinetic agents, and surgical intervention.

PMID- 29219647
TI  - What Would Cooper Do to You?

PMID- 29219648
TI  - Non-Q-wave myocardial infarction.
AB  - Preview Studies published since the early 1970s have changed the thinking about
      non-Q-wave myocardial infarction, and the serious nature of the disorder is now
      recognized. Reinfarction or infarct extension is the most common cause of
      morbidity in these patients. Thus, diagnosis with electrocardiography,
      appropriate choice of prophylactic measures, risk stratification before
      discharge, and careful follow-up are vital, as Dr Nixon discusses.

PMID- 29219649
TI  - What will Congress do to healthcare?
AB  - More than 6 months have passed since President Clinton presented his healthcare
      reform plan to Congress. Since then, Sen Phil Gramm (R, Texas) and several others
      have introduced healthcare reform bills. Will Congress eventually pass a bill on
      healthcare reform? What should physicians expect? We asked Senator Gramm to
      discuss his bill and to update physicians on how reform is shaping up.

PMID- 29219650
TI  - Kaiser Permanente's twist on managed care.
AB  - When many physicians think of managed care, they think first of Kaiser
      Permanente, the nation's largest HMO. That perception is misguided, according to
      David M. Lawrence, MD, the chief executive officer and chairman of the boards of
      the Kaiser Foundation health plan and hospitals. During a phone interview
      recently, Lawrence described managed care from his perspective at Kaiser and
      discussed Kaiser's place in the coming changes in healthcare delivery.

PMID- 29219652
TI  - Get off the fence and do something.

PMID- 29219651
TI  - You can't buy insurance when the house is on fire.
AB  - Why does health insurance cost so much? According to the vice president at the
      insurance company that pioneered high- deductible health insurance to go with
      medical savings accounts, a big factor is that insurance companies are being
      asked to solve social problems. Mr Hartnedy offers a solution to America's
      healthcare-delivery plight that includes empowerment of individuals and
      preservation of choice.

PMID- 29219654
TI  - IJRB: looking toward the future.

PMID- 29219653
TI  - Characteristics and outcome of intractable vasculitis syndrome in children:
      Nation-wide survey in Japan.
AB  - OBJECTIVE: Primary systemic vasculitis (PSV) is a rare disorder in children and
      difficult to distinguish from other diseases. However, appropriate diagnosis and
      prompt treatment will affect on the morbidity and mortality of intractable PSV.
      In this study, we conducted a nationwide survey in Japan, to clarify epidemiology
      and clinical outcome of PSV. METHODS: We had sent survey questionnaires to most
      of the Japanese institutions that employed pediatricians, requesting the number
      of patients with refractory PSV who were diagnosed and treated between 2007 and
      2011. Respondents were asked to provide detailed information on the clinical and
      laboratory features of each case they had managed. Those with Kawasaki disease or
      Henoch-Shonlein purpura vasculitis (IgA vasculitis) were excluded. RESULTS: Of
      all the institutions surveyed, 1123 (37.3%) patients responded, finally, total of
      49 patients with intractable PSV, defined by those with resistant to treatment
      and steroid-dependent, or with any complication associated with prognosis, were
      selected. The diagnosis was Takayasu arteritis in 31, polyarteritis nodosa in 11,
      granulomatosis with polyangitis in 2, microscopic polyangitis in 1, and ANCA
      negative microscopic polyangitis in 1. In those with Takayasu arteritis, 67% were
      treated with an immunosuppressive agent, 22% with biological modifiers, and 16%
      with surgical procedures. In other types of disease, 88% of the patients were
      treated with an immunosuppressive agent, and 12% with biological modifiers. Two
      with Takayasu arteritis died being terminally ill. CONCLUSION: This nationwide
      survey establishes the heterogeneous characteristics of PSV in children. Although
      questionnaire-based, the results of our analysis should be useful in planning
      prospective studies to identify the most effective therapy for each subtype of
      multifaceted disease.

PMID- 29219658
TI  - Urinary incontinence in women.
AB  - Preview Involuntary loss of urine is a troublesome, embarrassing problem among
      women. Fortunately, urinary incontinence can be treated, if not cured. What are
      the causes? When is surgical intervention appropriate? Which new nonsurgical
      treatment options are effective? The author answers these and other questions in
      this review of diagnostic tests and management options for urinary incontinence
      in women.

PMID- 29219657
TI  - The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 /
      ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.
AB  - The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently
      shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels
      of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in
      a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS
      or of mutant N-RAS, which was augmented in an additive to greater than additive
      fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce
      PDGFRalpha levels in GBM cells, that was enhanced by sodium valproate. Knock down
      of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium
      valproate / AR42 from reducing the expression of mutant N-RAS in established PDX
      and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and
      the drug combinations caused the co-localization of mutant RAS proteins and ERBB2
      with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent
      protein kinase that was causal in enhancing HMG Co A reductase phosphorylation.
      Collectively, our data reinforce the concept that the irreversible ERBB1/2/4
      inhibitor neratinib has the potential for use in the treatment of tumors
      expressing mutant RAS proteins.

PMID- 29219655
TI  - Track to the future: historical perspective on the importance of radiation track
      structure and DNA as a radiobiological target.
AB  - PURPOSE: Understanding the mechanisms behind induced biological response
      following exposure to ionizing radiation is not only important in assessing the
      risk associated with human exposure, but potentially can help identify ways of
      improving the efficacy of radiotherapy. Over the decades, there has been much
      discussion on what is the key biological target for radiation action and its
      associated size. It was already known in the 1930s that microscopic features of
      radiation significantly influenced biological outcomes. This resulted in the
      development of classic target theory, leading to field of microdosimetry and
      subsequently nanodosimetry, studying the inhomogeneity and stochastics of
      interactions, along with the identification of DNA as a key target. CONCLUSIONS:
      Ultimately, the biological response has been found to be dependent on the
      radiation track structure (spatial and temporal distribution of ionization and
      excitation events). Clustering of energy deposition on the nanometer scale has
      been shown to play a critical role in determining biological response, producing
      not just simple isolated DNA lesions but also complex clustered lesions that are
      more difficult to repair. The frequency and complexity of these clustered damage
      sites are typically found to increase with increasing LET. However in order to
      fully understand the consequences, it is important to look at the relative
      distribution of these lesions over larger dimensions along the radiation track,
      up to the micrometer scale. Correlation of energy deposition events and resulting
      sites of DNA damage can ultimately result in complex gene mutations and complex
      chromosome rearrangements following repair, with the frequency and spectrum of
      the resulting rearrangements critically dependent on the spatial and temporal
      distribution of these sites and therefore the radiation track. Due to limitations
      in the techniques used to identify these rearrangements it is likely that the
      full complexity of the genetic rearrangements that occur has yet to be revealed.
      This paper discusses these issues from a historical perspective, with many of
      these historical studies still having relevance today. These can not only cast
      light on current studies but guide future studies, especially with the increasing
      range of biological techniques available. So, let us build on past knowledge to
      effectively explore the future.

PMID- 29219659
TI  - Exercise training in patients with congestive heart failure.
AB  - Preview Inactivity adds to the decline of patients with congestive heart failure
      (CHF). However, in prescribing exercise in these patients, three principles must
      be understood: ejection fraction does not predict functional capacity, exercise
      can bring marked peripheral improvement without changing ejection fraction or
      hemodynamics, and benefits accrue slowly. The authors review the mechanisms of
      exercise intolerance in CHF and the factors to keep in mind when designing an
      exercise program.

PMID- 29219656
TI  - Modulating secreted components of tumor microenvironment: A masterstroke in tumor
      therapeutics.
AB  - The microenvironment in which cancer resides plays an important role in
      regulating cancer survival, progression, malignancy and drug resistance. Tumor
      microenvironment (TME) consists of heterogeneous number and types of cellular and
      non-cellular components that vary in relation to tumor phenotype and genotype. In
      recent, non-cellular secreted components of microenvironmental heterogeneity have
      been suggested to contain various growth factors, cytokines, RNA, DNA,
      metabolites, structural matrix and matricellular proteins. These non-cellular
      components have been indicated to orchestrate numerous ways to support cancer
      survival and progression by providing metabolites, energy, growth signals,
      evading immune surveillance, drug resistance environment, metastatic and
      angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer
      activities of these secreted components of TME has been considered as a new
      avenue in cancer therapeutics and drug resistance. In this report, we summarize
      the recent pre-clinical and clinical evidences to emphasize the importance of non
      cellular components of TME in achieving precision therapeutics and biomarker
      study.

PMID- 29219661
TI  - A Skunk in Gift Wrapping.

PMID- 29219660
TI  - Middle ear symptoms while flying.
AB  - Preview Few people can say they have never experienced some form of pressure
      related changes while flying. Although uncommon on commercial flights, severe
      middle ear blocks do occur. Drawing from his experience treating military pilots,
      Dr Brown discusses the causes of barotrauma, steps that airline passengers can
      take to prevent it, and methods for treating unrelenting ear block.

PMID- 29219662
TI  - Words from the Worldly.

PMID- 29219663
TI  - Common infections of the skin.
AB  - Preview Can you differentiate a furuncle from a carbuncle? Impetigo contagiosa
      from impetigo bullosa? Which treatment options are best for folliculitis and
      cellulitis? In this article, Dr Hacker discusses identification and management of
      skin infections that are commonly seen by primary care physicians. Helpful color
      photographs are included.

PMID- 29219664
TI  - Myofascial pain syndrome.
AB  - Preview The challenge of myofascial pain syndrome lies not only in the lack of
      specific accepted diagnostic criteria but also in the difficulty in eliciting
      specific physical responses. How, then, does the primary care physician approach
      clinical evaluation and treatment? The author discusses an approach that leads to
      early, aggressive treatment and an improved prognosis.

PMID- 29219665
TI  - Juvenile rheumatoid arthritis.
AB  - Preview What are the three main types of disease presentation in juvenile
      rheumatoid arthritis, and how do they relate to prognosis? Does infection or
      heredity play a role in causing the illness? Should aggressive therapy with
      multiple drugs be instituted early? Which therapeutic agents have the best chance
      of inducing remission? Dr Tibbitts addresses these and other questions in this
      overview of a disease that is a significant cause of chronic illness and
      disability in children.

PMID- 29219667
TI  - Endothelial biology and ATP-sensitive potassium channels.

PMID- 29219666
TI  - Coincidence of celiac disease with nongastrointestinal tumors in children.
AB  - The association of celiac disease (CD) with cancers of gastrointestinal origin
      has been noted. However, coincidence of CD with nongastrointestinal neoplasms is
      an unusual event. Here we present five children with concurrent CD and
      nongastrointestinal neoplasms. All of the patients had positive serologic results
      for anti-tTG antibodies. Histological investigation of intestinal mucosa showed
      inflammation (Marsh score = 2) in all the patients. Two of these patients
      represented with germ cell malignancies. One patient had Wilms' tumor. To our
      knowledge, these are the first reports of coincidence of these two cancers with
      CD in children. From the remaining two patients, one was diagnosed with acute
      lymphoblastic leukemia, and the other with astrocytoma. The diagnosis of
      malignancy preceded CD diagnosis in all the patients (mean ages of cancer and CD
      diagnosis of 1.8 and 5.4 years old, respectively). Whether malignancy can promote
      immune deregulation and predispose to CD is uncertain. On the other hand,
      undiagnosed celiac may be a risk factor for cancer. Our results suggest a
      potential association of CD with malignancy nature of CD, however, occurrence of
      CD may be influenced by various intrinsic and extrinsic factors. There are few
      reports noting CD as a paraneoplastic condition. Further investigations are
      necessitated to stablish such relationship.

PMID- 29219668
TI  - Multispectral imaging reveals hyper active TGF-beta signaling in colorectal
      cancer.
AB  - Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology
      platforms allow quantification of multiple proteins at same tissue section and
      produce continuous data. TGF-beta signaling plays crucial and complex roles in
      colorectal cancer (CRC). We here aimed to investigate clinical pathological
      relevant of proteins involved in TGF-beta signaling at CRC tissues. Multiplex
      fluorescent IHC was used to quantitative analysis. The levels of eight proteins
      (TGF-beta1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p
      SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out
      by a scoring system by InForm software. It revealed that TGF-beta signaling was
      hyper active. The levels of TGF-beta1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p
      SMAD2/3 were significantly increased in cancer tissues when compared their levels
      in normal tissues. Furthermore, the levels of eight proteins in stroma were
      significantly lower than the levels that in cancer tissues. Clinical pathological
      relevant analysis exhibited that TGF-beta signaling inclined to suppress the
      progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant
      predictors for overall survival. In conclusion, we established a method based on
      multispectral imaging to extensively explore the clinical relevant of TGF-beta
      signaling proteins. These results provided an opportunity to consider the novel
      application for proteins involving TGF-beta signaling that used as diagnostic or
      prognostic biomarkers to conduct tumor therapy.

PMID- 29219669
TI  - Metabolic profile elucidation of Zhi-Zi-Da-Huang decoction in rat intestinal
      bacteria using high-resolution mass spectrometry combined with multiple
      analytical perspectives.
AB  - 1. Zhi-Zi-Da-Huang decoction (ZZDHD) has been widely used for the treatment of
      alcoholic jaundice, alcoholic liver disease, and acute hepatitis in China for
      thousands of years. Conventionally decoctions are administered orally, after
      which the metabolism caused by the enzymes in intestinal bacteria may influence
      significantly on the curative effects or toxicity. 2. In this work, the
      comprehensive metabolic process of ZZDHD in intestinal bacteria was investigated
      reliably using high-resolution HPLC-DAD-ESI-TOF/MS. Besides, a novel strategy for
      major-to-trace metabolites identification which integrated information derived
      from diagnostic fragment ions, mass spectral similarity filter strategy, dynamic
      metabolic change of target compounds and relevant behavior in LC-MS was adopted.
      3. As a result, 45 compounds, including 26 bio-converted prototypes and 19 newly
      generated metabolites were detected and tentatively identified. The metabolic
      profile of ZZDHD in gastro-intestinal was subsequently elucidated.
      Deglycosylation, oxidation, reduction, acetylation, and ring cleavage were all
      observed in the biotransformation of the decoction. Among the rest,
      deglycosylation was found to be the predominant metabolic pathway. 4. The results
      obtained herein provided a practical strategy for metabolic profile elucidation
      of traditional herbal medicines. Moreover, it would be helpful to unravel how the
      oral decoctions play the therapeutic role in vivo.

PMID- 29219670
TI  - Expanding the use of abiraterone in prostate cancer: Is earlier always better?

PMID- 29219671
TI  - Idiopathic retroperitoneal fibrosis: a cross-sectional study of 142 Chinese
      patients.
AB  - OBJECTIVE: To investigate the epidemiological, clinicolaboratory, imaging, and
      therapeutic characteristics of idiopathic retroperitoneal fibrosis (iRPF) in
      China. METHOD: All patients presenting to the Chinese People's Liberation Army
      General Hospital from October 1996 to July 2016 diagnosed with iRPF were
      included. Data were collected from medical records and the smoking index was
      calculated. Scheel radiological classification was used to assess the extent of
      soft-tissue density. RESULTS: The study included 142 patients (120 men, 22
      women). The mean age was 54.3 years. Disease duration ranged from 0.23 to 109.5
      months (median 2.7). Current smoking rate was 53.5%. Flank pain was more common
      in males (p = 0.041) and in the high smoking index group (p = 0.03). C-reactive
      protein level ranged from 0.08 to 8.9 mg/dL (median 1.9). Serum immunoglobulin G4
      (IgG4) was elevated in 31/63 patients (49.2%), and males had higher IgG4
      concentrations (p = 0.017) at presentation. Respectively, 44.4%, 5.6%, and 22.5%
      of cases were classified into Scheel classes I, II, and III. Eight patients
      (5.6%) had atypical RPF localization and 103 (72.5%) presented with
      hydronephrosis, which was more common in class III patients (p = 0.04). Nine
      patients (6.3%) received no treatment; the others received medical (34.5%) or
      surgical treatment (14.8%), or both (44.4%). CONCLUSIONS: There was a higher rate
      in males and younger age at disease onset in these Chinese iRPF patients than in
      other populations. Acute-phase reactants and serum IgG4 were elevated in some
      patients. Tobacco use may be a risk factor for iRPF in Chinese populations.

PMID- 29219672
TI  - Diffuse pulmonary infiltrates in immunocompromised patients.
AB  - Preview The approach to immunocompromised patients with diffuse pulmonary
      infiltrates has become increasingly complex with the evolution of more intense
      immunosuppressive therapy. Controversy still exists regarding the use of invasive
      diagnostic procedures rather than empirical therapy for this heterogeneous group.
      Dr Staszewski explains the reasons for the uncertainty and recommends an
      individualized approach that takes into account type of immunosuppression, local
      resources, physician experience, and patient prognosis.

PMID- 29219673
TI  - How to help your patients quit smoking.
AB  - Preview Motivating patients to quit smoking is one of the greatest challenges in
      medicine. The adverse effects of smoking on a patient's general health and the
      enormous cost of the habit to society should make smoking cessation a priority
      for physician intervention. In this article, Dr Wong discusses the addictive
      properties of nicotine and the consequences of giving it up and outlines a simple
      four-step approach to behavior modification.

PMID- 29219674
TI  - Out of Character.

PMID- 29219675
TI  - Reversing coronary atherosclerosis.
AB  - Preview Results of recently completed and ongoing trials may change the thinking
      on how to treat atherosclerosis. For example, even faithful adherence to the
      American Heart Association step 2 diet may not halt progression of established
      coronary artery disease. Also, current goals of lipid-lowering therapy may be
      inadequate to reverse coronary artery narrowings. Dr Kahn describes studies that
      have used more drastic measures to control hyperlipidemia, the effects of these
      measures on coronary atherosclerosis, and clinical application of results.

PMID- 29219676
TI  - Maternal sexual abuse of male children.
AB  - Preview Sexual abuse of boys by their mothers is being increasingly reported and
      must be considered in the course of history taking and physical examination.
      Often there is little objective evidence of such abuse, and only a cluster of
      signs and risk factors may reveal the victimization. Drs Elliott and Peterson
      list characteristics that can help physicians identify sexually abusive mothers
      and sexually abused children; they also discuss how to retrieve a report of abuse
      from a child and assess its credibility.

PMID- 29219677
TI  - Rectal cancer.
AB  - Preview When in rectal cancer surgery can the anal sphincter be spared? For which
      patients is iliac lymphadenectomy advisable? Should radiation therapy and
      chemotherapy be given before surgery rather than after? Drs Sexe and Miedema
      address these and other questions in this discussion of recent advances and
      future trends in therapy for rectal cancer.

PMID- 29219678
TI  - 'Clinton & Clinton' Tort Reform.

PMID- 29219679
TI  - Erythema migrans.
AB  - Preview Because disseminated Lyme disease can be devastating, early recognition
      and treatment are important. The presence of erythema migrans offers the best
      opportunity for early diagnosis. Therefore, public awareness and patient
      education about the rash of Lyme disease are critical. Dr Masters gives practical
      pointers from his own experience in evaluation of erythema migrans and reviews
      current treatment recommendations.

PMID- 29219681
TI  - Thyroid nodules.
AB  - Preview Fine-needle aspiration biopsy is not unerring as a diagnostic tool in
      patients with thyroid nodules, but study has shown that its use has strikingly
      decreased the necessity for surgery and has almost doubled the number of cancers
      found at operation. Dr Wool examines the application of the procedure for thyroid
      nodules and presents a comprehensive algorithm for diagnosis and treatment of
      these common lesions.

PMID- 29219680
TI  - Ankylosing spondylitis.
AB  - Preview Back pain can be a symptom of any number of problems, most commonly
      mechanical, or structural, in nature. Among the nonmechanical causes is
      ankylosing spondylitis, an inflammatory disease that involves the spine and
      sometimes other joints and extra-articular organs. Dr Escalante explains how to
      differentiate this disease from other causes of back pain, describes simple
      clinical diagnostic tests, and outlines current treatment. The condition's link
      with HLA-B27 is also discussed.

PMID- 29219682
TI  - Thyroid function tests.
AB  - Preview Use and interpretation of thyroid function tests have long been sources
      of confusion. New methods for estimating serum free thyroxine levels and
      development of more sensitive assays for thyrotropin have provided the major
      advances in thyroid function testing in the past decade. In this article, Dr Kaye
      examines the newer thyroid function tests and their application in the evaluation
      of hypothyroidism, hyperthyroidism, and nonthyroidal illness.

PMID- 29219683
TI  - Subclinical hypothyroidism.
AB  - Preview What causes subclinical hypothyroidism? How prevalent is it? When is it
      likely to progress to overt disease? Are clinical abnormalities sometimes
      present? Answers to these questions, as well as a discussion of treatment
      approaches, are found in this overview.

PMID- 29219684
TI  - Oncologic emergencies.
AB  - Preview A wide variety of medical emergencies may develop in patients with
      cancer. Some of the more common ones can be anticipated and prevented; others are
      less predictable, especially those caused by the newer chemotherapy regimens.
      When emergencies occur, the earlier diagnosis is made and treatment begun, the
      greater the opportunity for improved quality of life and survival. Dr Neilan
      focuses on the most timely aspects of management.

PMID- 29219685
TI  - Management of depression.
AB  - Preview "Do you feel depressed at times?" "Do you ever feel that life is not
      worth living?" "Have you ever thought about ending your life?" Asking such
      questions during history taking may help save the life of a patient struggling
      with depression. Dr Citrome describes the diagnostic criteria for major
      depression and discusses current treatment options, including traditional
      antidepressant drugs and the newer serotonin-reuptake inhibitors.

PMID- 29219686
TI  - Focal liver lesions.
AB  - Preview Focal liver lesions are occasionally encountered in clinical practice,
      either during a directed evaluation in a symptomatic patient or as an incidental
      finding during radiologic imaging, laparoscope or laparotomy for some other intra
      abdominal condition. In this article, the first of two, the authors discuss the
      steps in evaluating cystic focal liver lesions and present a systematic approach
      to their diagnosis and treatment. A companion article, on page 157, focuses on
      the management of solid lesions.

PMID- 29219687
TI  - The 'Food Security Act of 1995.

PMID- 29219688
TI  - Focal liver lesions.
AB  - Preview Solid focal lesions of the liver can present numerous diagnostic
      challenges, and once diagnosis is made, careful decision making is needed to
      assure cost-effective management. In this article, the authors consider five
      solid lesions: hemangioma, focal nodular hyperplasia, liver cell adenoma, primary
      hepatocellular carcinoma, and metastatic cancer. Cystic lesions are assessed in a
      companion article on page 149.

PMID- 29219689
TI  - Closing in on Jargon.

PMID- 29219690
TI  - Calcium channel antagonists.
AB  - Preview The success of calcium channel antagonists in controlling hypertension,
      angina pectoris, and arrhythmias is well known. In recent years, second
      generation agents have been introduced that are also effective against migraine
      headaches and Raynaud's phenomenon and appear to improve atherosclerosis and
      congestive heart failure. The authors summarize the characteristics that calcium
      channel antagonists have in common and describe the specific niche filled by the
      newer agents, particularly those of the dihydropyridine class.

PMID- 29219691
TI  - Pediatric HIV infection and the primary care physician.
AB  - Preview In many children with HIV infection, the disease has a slowly progressive
      course during the preadolescent years. These children have special healthcare
      needs because of their increased risk of life-threatening infections and variable
      immune response to vaccines. In this article, Dr Flynn reviews the many unique
      aspects of providing medical care for a group whose numbers continue to grow.

PMID- 29219692
TI  - Opportunistic infections in AIDS patients.
AB  - Preview The type and course of opportunistic infections in patients with AIDS or
      high-risk HIV infection have changed through the years as a result of therapeutic
      intervention. Although Pneumocystis carinii pneumonia is still the most common
      and serious infection, its incidence is declining at the same time that other
      AIDS-defining illnesses are on the rise. Dr Hughes examines the management of
      major opportunistic infections and also of tuberculosis, which is becoming more
      prevalent in association with HIV infection.

PMID- 29219693
TI  - Lower Extremity Ischemia.
AB  - Preview Being able to walk without assistance is integral to preserving quality
      of life. Losing this ability in later years as a result of ischemic arterial
      lesions in the legs can be devastating. Primary care physicians are in a good
      position to detect early problems and advise patients on how to improve the
      condition or prevent progression. In addition, primary care physicians are an
      important part of the team needed to manage the most severe, limb-threatening
      cases.

PMID- 29219694
TI  - Recurrent pneumococcal meningitis.
AB  - Preview Recurrent bacterial meningitis can be caused by acquired or congenital
      gross anatomic defects, foci of infection, or disorders in immune mechanisms. The
      diagnosis of occult sinus fracture can be a challenge and, as in the patient
      described here, requires a high index of suspicion when a child has a remote
      history of head injury and repeated episodes of meningitis.

PMID- 29219695
TI  - Lactose Intolerance.
AB  - Preview Lactose intolerance is highly prevalent among certain ethnic populations
      and should be suspected when evaluating gastrointestinal complaints in members of
      such groups. The disorder can be associated with many intestinal diseases and
      with medication use, and in rare instances it is congenital. The authors discuss
      methods of clinical evaluation and offer basic dietary recommendations for
      patients with lactose intolerance.

PMID- 29219697
TI  - The many guises of amyloidosis.
AB  - Preview Amyloidosis can present in myriad ways and is often confused with other
      diseases. To help physicians avoid diagnostic pitfalls, Drs Vogelgesang and
      Klipple describe the various clinical amyloid syndromes, tell what differentiates
      them, and summarize the effects of amyloid infiltration on various organ systems.
      They also assess the effectiveness of diagnostic techniques and note the relative
      ineffectiveness of medications that have been used to treat amyloidosis.

PMID- 29219698
TI  - Estrogen replacement therapy at menopause.
AB  - Preview Bone loss and cardiovascular disease are the most important complications
      of menopause. Because estrogen has been shown to prevent bone loss and also
      reduce fracture rates in menopausal women, the authors recommend early
      replacement therapy. They also examine evidence that estrogen replacement may
      offer these women protection from cardiovascular disease and discuss the risks of
      estrogen-related endometrial and breast cancer.

PMID- 29219699
TI  - Two ear problems you may not need to refer.
AB  - Preview Can you differentiate eczematous otitis externa from fungal otitis
      externa? Do you know what causes acute otitis externa? How to treat bullous
      myringitis? An otolaryngologist describes these and other conditions in this
      article, which is intended to help primary care physicians manage two commonly
      referred otologic problems and, most importantly, know when to refer patients for
      subspecialty care.

PMID- 29219696
TI  - Detailed secondary structure models of invertebrate 7SK RNAs.
AB  - The 7SK RNA is a small nuclear RNA that is involved in the regulation of Pol-II
      transcription. It is very well conserved in vertebrates, but shows extensive
      variations in both sequence and structure across invertebrates. A systematic
      homology search extended the collection of 7SK genes in both Arthropods and
      Lophotrochozoa making use of the large number of recently published invertebrate
      genomes. The extended data set made it possible to infer complete consensus
      structures for invertebrate 7SK RNAs. These show that not only the well-conserved
      5'- and 3'- domains but all the interior Stem A domain is universally conserved.
      In contrast, Stem B region exhibits substantial structural variation and does not
      adhere to a common structural model beyond phylum level.

PMID- 29219700
TI  - Hereditary hemochromatosis.
AB  - Preview Hereditary hemochromatosis, once believed to be rare, is now known to
      affect 1 in 250 to 300 people of northern European descent. Untreated, the
      disorder can have serious complications, but for patients in whom it is
      discovered and treated early, the prognosis is good. In this guide to diagnosis
      and management, Drs Olynyk and Bacon discuss, among other things, which patients
      to screen, what tests to order, length of treatment, effect of treatment on
      complications, and prognosis.

PMID- 29219701
TI  - Will Congress Change Hands?

PMID- 29219703
TI  - A Lifetime of Half-Truths.

PMID- 29219702
TI  - Congestive heart failure.
AB  - Preview Patients with congestive heart failure generally have a poor prognosis,
      and sudden death is common. Concepts of management have changed drastically
      through the years, in hopes that predisposing factors can be modified. In this
      article, Drs Hobbs and Czerska give an overview of the problem and examine the
      status of pharmacologic therapy and various surgical techniques.

PMID- 29219704
TI  - How to help diabetic patients avoid amputation.
AB  - Preview Of the 14 million Americans who have diabetes mellitus, more than 2
      million will at some point have foot ulcers. The prevalence of this complication,
      its impact on the activities of daily living, and the cost of treating it make it
      a problem of immense magnitude. Primary care physicians who emphasize prevention
      and early treatment of foot ulcers can greatly reduce the likelihood of serious
      sequelae. This article tells you what to look for in examining the feet, how to
      advise patients in foot care, and what to do if ulcers occur despite preventive
      efforts.

PMID- 29219705
TI  - Transient ischemic attacks.
AB  - Preview All transient ischemic attacks are not created equal. However, they are a
      medical emergency, and all patients should be hospitalized for urgent evaluation
      of their risk for stroke or myocardial infarction. For optimal management, it
      must be determined whether an ischemic attack affects the anterior or posterior
      circulation. In this article, the authors review current medical options for
      stroke prevention and the indications for carotid endarterectomy.

PMID- 29219706
TI  - Elevated thyroxine levels in a euthyroid patient.
AB  - Preview Euthyroid hyperthyroxinemia is often misdiagnosed, resulting in
      inappropriate treatment with ablation or surgical removal of the thyroid gland.
      Therefore, it is important that primary care physicians be familiar with the
      causes of this disorder. This case report describes the diagnostic approach taken
      in one patient and discusses normal thyroid physiology.

PMID- 29219707
TI  - Carotid artery stenosis.
AB  - Preview Many patients with significant carotid artery stenosis are candidates for
      endarterectomy, a procedure now proved to reduce the incidence of future stroke
      and death. In this article, Drs Jaigobin and Perry describe an approach to
      patients with both symptomatic and asymptomatic carotid stenosis and review
      current indications for surgical referral. They also emphasize the importance of
      recognizing and managing concurrent coronary artery disease.

PMID- 29219708
TI  - Management of acute stroke.
AB  - Preview Regardless of cause, acute stroke is a devastating illness that demands
      immediate treatment to contain neurologic damage, plus long-term management to
      assure utmost rehabilitation. In this article, the authors describe the features
      of stroke from various causes and discuss current therapy.

PMID- 29219709
TI  - Acute renal failure.
AB  - Preview An abrupt decrease in the kidneys' ability to excrete waste products is a
      common cause of severe morbidity and death in critically ill patients. This
      complication may result from prerenal, renal parenchymal, or postrenal causes.
      The authors describe the clinical and laboratory evaluation of acute renal
      failure and offer an approach to prevention and appropriate management.

PMID- 29219710
TI  - SNX1-mediated protein recycling: Piecing together the tissue-specific regulation
      of arabidopsis iron acquisition.
AB  - Endomembrane protein trafficking has emerged as important means of regulating
      stress responses in plants. The Arabidopsis SNX1 protein is involved in recycling
      the iron transporter IRT1, thus promoting its presence at the plasma membrane.
      SNX1 and its interacting partners undergo stress-related regulation at both
      transcriptional and posttranslational level, which may include differential
      regulation at tissue level. Based on this, we explore the tissue-specific
      regulation of iron import, specifically concentrating on the factors involved in
      the expression and recycling of IRT1 in root tissues. We propose that different
      processes affecting IRT1 regulation may lead to similar outcomes, allowing for
      fine-tuning iron acquisition and distribution.

PMID- 29219711
TI  - Insulin therapy and the reluctant patient.
AB  - Preview When diabetic patients learn that insulin therapy is necessary, they may
      fee) overwhelmed by anticipated changes in lifestyle. The key to success is to
      realize that every person with diabetes has individual needs and that these must
      be assessed, addressed, and accommodated. Better diabetes control will be the
      result.

PMID- 29219712
TI  - Kawasaki syndrome.
AB  - Preview Misdiagnosis of Kawasaki syndrome is common, because some of its signs
      (eg, unremitting fever, conjunctival injection, rash) resemble viral infection
      and there are no laboratory tests to establish the diagnosis. Dr Applegate
      illustrates features of the disease with a case report and summarizes currently
      favored treatment. She also stresses close follow-up, since Kawasaki syndrome has
      replaced acute rheumatic fever as the leading cause of acquired heart disease in
      children.

PMID- 29219713
TI  - Liver transplantation.
AB  - Preview How many months of documented abstinence are required before a patient
      with alcoholic cirrhosis can be considered for liver transplantation? What is the
      role of liver transplantation as treatment for primary hepatocellular cancer?
      What are the possible causes of elevated liver enzyme levels following
      transplantation? Which patients with neurologic injury are potential organ
      donors? The authors answer these and other questions primary care physicians may
      have about this lifesaving procedure.

PMID- 29219714
TI  - Bronchiectasis.
AB  - Preview A host of congenital and acquired conditions may lead to chronic
      dilatation of the bronchi, or bronchiectasis. What are the most common clinical
      signs of the disease? Which diagnostic tests are most helpful in pinpointing the
      underlying disorder? In this article, Drs Marwah and Sharma address these
      questions and review treatment options and key elements of prevention.

PMID- 29219715
TI  - Diagnosis of chest pain.
AB  - Preview Although electrocardiographic stress tests are valuable in providing
      prognostic information about patients with coronary artery disease, the author
      believes that they are often overused in the diagnosis of chest pain. In this
      article, he presents indications and contraindications to stress testing and
      discusses cost-effective management strategies.

PMID- 29219716
TI  - Random Acts of Kindness.

PMID- 29219717
TI  - Acute inflammation after injury.
AB  - Preview Although many people know something about the RICE technique to treat
      musculoskeletal injury, few use it correctly or long enough. As Dr Baumert
      explains, the sooner inflammation is controlled, the less damage is done and the
      sooner rehabilitation can begin. He describes appropriate use of physical and
      medical modifiers in arresting the inflammatory process and proper choice of
      therapeutic exercises to restore range of motion, strength, and endurance.

PMID- 29219718
TI  - Shoulder problems in athletes.
AB  - Preview Because the pathoanatomy of shoulder problems in athletes is becoming
      better understood, a straightforward approach to diagnosis and treatment based on
      careful history taking and physical examination is feasible. Imaging techniques
      are greatly improved, but the clinical examination remains the keystone of
      management. Most shoulder problems are treated nonoperatively, and athletes are
      usually able to return to sports quickly and safely.

PMID- 29219719
TI  - Management of concussion in collision sports.
AB  - Preview Concussions are common in collision sports, and potentially catastrophic.
      Team physicians need to be adept at recognizing them and grading their severity.
      When can an athlete who has experienced a concussion safely return to
      competition? What clinical findings point to skull fracture? What symptoms call
      for neuroimaging? Dr Fick addresses these and other questions in this valuable
      overview aimed at physicians with limited experience in sidelines management of
      head injuries.

PMID- 29219720
TI  - Sickle cell disease.
AB  - Preview Early diagnosis of sickle cell disease enables physicians to initiate
      prompt treatment and provide appropriate education and counseling for patients
      and their families. In this article, Dr Burdick reviews the management of major
      complications of the disorder, discusses the psychosocial impact, and examines
      the possibilities for cure in the future.

PMID- 29219722
TI  - Now, Time for Some Changes at AMA?

PMID- 29219721
TI  - Obsessive-compulsive disorder.
AB  - Preview Enormous amounts of time and energy may be consumed by persons with
      obsessive-compulsive disorder, who think distressing thoughts and then feel
      compelled to act on them repeatedly. How common is obsessive-compulsive disorder?
      What are its typical clinical presentations? The authors of this article answer
      these questions and discuss pharmacologic and behavior therapy.

PMID- 29219723
TI  - On (Holiday) Call.

PMID- 29219724
TI  - Thrombolysis after acute myocardial infarction.
AB  - Preview Physicians know that thrombolysis has marked benefits in patients with
      certain classic findings after acute myocardial infarction. However, some do not
      realize that thrombolysis has relatively limited risks and can be administered to
      many more patients than it is at present. The authors review current indications
      and contraindications and summarize results of major clinical studies that
      compare currently available thrombolytic agents.

PMID- 29219725
TI  - Adjuvants to thrombolysis after acute myocardial infarction.
AB  - Preview In patients who have experienced myocardial infarction, re-occlusion of
      the affected vessel is disappointingly common. A variety of agents, strategies,
      and combination approaches have been tried as adjuncts to thrombolysis in an
      effort to improve left ventricular function, morbidity, and mortality in these
      patients. The authors summarize findings of these clinical trials, some of which
      are still under way.

PMID- 29219511
TI  - Search for Heavy Higgs Bosons A/H Decaying to a Top Quark Pair in pp Collisions
      at sqrt[s]=8  TeV with the ATLAS Detector.
AB  - A search for heavy pseudoscalar (A) and scalar (H) Higgs bosons decaying into a
      top quark pair (tt[over -]) has been performed with 20.3  fb^{-1} of proton
      proton collision data collected by the ATLAS experiment at the Large Hadron
      Collider at a center-of-mass energy sqrt[s]=8  TeV. Interference effects between
      the signal process and standard model tt[over -] production, which are expected
      to distort the signal shape from a single peak to a peak-dip structure, are taken
      into account. No significant deviation from the standard model prediction is
      observed in the tt[over -] invariant mass spectrum in final states with an
      electron or muon, large missing transverse momentum, and at least four jets. The
      results are interpreted within the context of a type-II two-Higgs-doublet model.
      Exclusion limits on the signal strength are derived as a function of the mass
      m_{A/H} and the ratio of the vacuum expectation values of the two Higgs fields,
      tanbeta, for m_{A/H}>500  GeV.

PMID- 29219726
TI  - Alcoholic hepatitis.
AB  - Preview Liver damage due to alcohol abuse is a severe condition often leading to
      cirrhosis or death. Unfortunately, the exact mechanisms involved are not well
      understood, and traditional treatment options have had limited success in
      improving morbidity and mortality rates. The authors of this article review
      recent studies on pathogenesis and discuss the pros and cons of current medical
      and surgical management.

PMID- 29219727
TI  - Acute exacerbations of chronic bronchitis.
AB  - Preview Acute bacterial exacerbations of chronic bronchitis cause considerable
      morbidity and mortality, particularly in the elderly. Effective antimicrobial
      therapy results in fewer hospitalizations for respiratory failure and better
      resolution of symptoms. However, there is growing concern regarding treatment
      failures caused by resistant organisms. The authors therefore describe the
      activity of pharmacologic agents from different classes and indicate which ones
      may be considered primary treatment for this serious condition.

PMID- 29219728
TI  - Skin signs of systemic disease.
AB  - Preview Few primary care physicians may have encountered facial trichilemmomas,
      Gottron's papules, or erythema chronicum migrans in their practice. However,
      recognition of these skin lesions can be the key to diagnosis of underlying
      systemic diseases. Drs Holmes and Massa review the diagnostic features of several
      systemic conditions that have prominent skin signs.

PMID- 29219734
TI  - Neuromuscular diseases of the gastrointestinal tract.
AB  - Preview When traditional testing fails to identify a cause of common
      gastrointestinal problems such as abdominal pain, bloating, and diarrhea, the
      symptoms are sometimes lumped under a general diagnosis of functional or
      irritable bowel disease. However, the cause may be a well-defined organic
      condition, recognizable by its signs and symptoms and by results of more
      specialized testing. The authors describe mechanisms and characteristics of five
      neuromuscular diseases, as well as promising therapeutic agents.

PMID- 29219731
TI  - Methadone maintenance treatment.
AB  - Preview Substance abuse, particularly injecting drug use, is receiving increased
      attention because of its role in the spread of AIDS. Methadone maintenance
      treatment programs help curb the spread by decreasing injecting drug abuse and by
      offering HIV testing, counseling, and referral for care of infected patients. Drs
      DeMaria and Weinstein explain how methadone programs work and what primary care
      physicians need to know to refer their opiate-dependent patients.

PMID- 29219732
TI  - A practical approach to dizziness.
AB  - Preview Sorting out a patient's complaint of dizziness can be almost as
      disorienting to the physician as the dizziness is to the patient. Some of the
      confusion may be due to the variety of symptoms that often accompany dizziness
      and the hard-to-describe nature of the symptoms. But another factor may be that
      physicians lack a systematic approach to the problem. Dr Ruckenstein provides a
      stepwise method of evaluating dizziness built around a set of pertinent,
      progressive questions.

PMID- 29219733
TI  - Reiter's syndrome.
AB  - Preview Reiter's syndrome is an often overlooked and misdiagnosed complex of
      symptoms. Patients may not present with the classic triad of symptoms, or they
      may forget to mention other pertinent manifestations. How can you make an
      accurate diagnosis? And what is an effective approach to management? Dr Kirchner
      reviews studies on the epidemiology, causes, and pathogenesis of the syndrome and
      discusses key factors in clinical evaluation and treatment.

PMID- 29219736
TI  - Hantavirus pulmonary syndrome.
AB  - Preview An alarming new disease was first reported in mid-1993, and by late 1994,
      almost 100 cases had been identified nationwide. Mild prodromal flulike symptoms
      were followed within days by rapidly progressive respiratory illness and early
      death. Cooperative efforts of many agencies soon established the cause- a
      previously unidentified hantavirus. Thus, the disease was named hantavirus
      pulmonary syndrome. Dr Levy describes the outbreak and summarizes features of the
      syndrome and recommendations on prevention.

PMID- 29219738
TI  - Other People's Money.

PMID- 29219739
TI  - Transesophageal echocardiography.
AB  - Preview Echocardiography is invaluable in assessing patients with known or
      suspected cardiac disorders. However, there are often impediments to adequate
      imaging using the standard transthoracic route (eg, mechanical ventilation,
      bandages). Transesophageal imaging overcomes many of these technical limitations
      and, as one researcher notes, provides a "new window to the heart." Drs Peterson
      and Orsinelli review common clinical applications of the procedure and adjunctive
      uses.

PMID- 29219735
TI  - Menstrual dysfunction in athletes.
AB  - Preview As more and more women participate in competitive sports, disorders of
      menstrual function and the resultant risk of skeletal injury have become
      significant concerns. Primary care physicians can have a key role in identifying
      patients at risk and helping them to stay active while avoiding serious
      morbidity. Dr DiFiori discusses the relationship between menstrual dysfunction
      and loss of bone mineral density and offers a practical approach to evaluation
      and treatment.

PMID- 29219737
TI  - Eosinophilia of the blood.
AB  - Preview A patient has an abnormally high concentration of eosinophils in the
      blood, but initial clinical and laboratory evaluation offers no clues as to the
      cause. The authors of this article describe such a case and the course of action
      they took to establish an unexpected diagnosis. Differential diagnosis of
      eosinophilia is the focus of their discussion.

PMID- 29219740
TI  - Diagnostic cardiac catheterization.
AB  - Preview The risks associated with diagnostic cardiac catheterization have
      declined through the years, but the question remains as to which patients should
      be referred for the procedure. In this article, Drs Walder and Schaller examine
      present guidelines for different types of heart disease and also review
      qualifications for performing cardiac catheterization.

PMID- 29219729
TI  - Drought stress responses in maize are diminished by Piriformospora indica.
AB  - As an endophytic fungus of Sebacinales, Piriformospora indica promotes plant
      growth and resistance to abiotic stress, including drought. Colonization of maize
      roots promoted the leaf size, root length and number of tap roots. Under drought
      stress, the maize seedlings profited from the presence of the fungus and
      performed visibly better than the uncolonized controls. To identify genes and
      biological processes involved in growth promotion and drought tolerance conferred
      by P. indica, the root transcriptome of colonized and uncolonized seedlings was
      analyzed 0, 6 and 12 h after drought stress (20% polyethylene glycol 6000). The
      number of P. indica-responsive genes increased from 464 (no stress at 0 h) to
      1337 (6 h drought) and 2037 (12 h drought). Gene Ontology analyses showed that
      the carbon and sulfur metabolisms are major targets of the fungus. Furthermore,
      the growth promoting effect of P. indica is reflected by higher transcript levels
      for microtubule associated processes. Under drought stress, the fungus improved
      the oxidative potential of the roots, and stimulated genes for hormone functions,
      including those which respond to abscisic acid, auxin, salicylic acid and
      cytokinins. The comparative analyses of our study provides systematic insight
      into the molecular mechanism how P. indica promotes plant performance under
      drought stress, and presents a collection of genes which are specifically
      targeted by the fungus under drought stress in maize roots.

PMID- 29219741
TI  - Central venous catheters.
AB  - Preview Placement of a central venous catheter is not without risk. If the tip of
      the catheter either is inadvertently positioned within the heart or migrates into
      it, vascular erosions may develop and result in perforation and death. In this
      article, Dr Kahn gives the advantages and disadvantages of the usual routes of
      insertion and describes monitoring techniques. He also suggests methods of
      avoiding initial intracardiac placement.

PMID- 29219730
TI  - A comprehensive profile of circulating RNAs in human serum.
AB  - Non-coding RNA (ncRNA) molecules have fundamental roles in cells and many are
      also stable in body fluids as extracellular RNAs. In this study, we used RNA
      sequencing (RNA-seq) to investigate the profile of small non-coding RNA (sncRNA)
      in human serum. We analyzed 10 billion Illumina reads from 477 serum samples,
      included in the Norwegian population-based Janus Serum Bank (JSB). We found that
      the core serum RNA repertoire includes 258 micro RNAs (miRNA), 441 piwi
      interacting RNAs (piRNA), 411 transfer RNAs (tRNA), 24 small nucleolar RNAs
      (snoRNA), 125 small nuclear RNAs (snRNA) and 123 miscellaneous RNAs (misc-RNA).
      We also investigated biological and technical variation in expression, and the
      results suggest that many RNA molecules identified in serum contain signs of
      biological variation. They are therefore unlikely to be random degradation by
      products. In addition, the presence of specific fragments of tRNA, snoRNA, Vault
      RNA and Y_RNA indicates protection from degradation. Our results suggest that
      many circulating RNAs in serum can be potential biomarkers.

PMID- 29219742
TI  - Dietary exposure and risk assessment of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans and dioxin-like polychlorinated biphenyls of the
      population in the Region of Valencia (Spain).
AB  - Dietary exposure of the Valencia Region population to polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and PCBs was assessed in
      the Region of Valencia in 2010-2011. A total of 7700 food samples were collected.
      Occurrence data were combined with consumption data to estimate dietary exposure
      in adults (>15 years of age) and young people (6-15 years of age). The estimated
      intake was calculated by a probabilistic approach. Average intake levels (upper
      bound scenario) were 1.58 and 2.76 pg toxic equivalent (TEQ) kg-1 body weight
      (bw) day-1 for adults and young people, respectively. These average intakes are
      within range of the tolerable daily intake of 1-4 pg WHO-TEQ kg-1 bw day-1
      recommended by WHO, and slightly above the tolerable weekly intake (TWI) of 14 pg
      TEQ kg-1 bw week-1 and the Provisional tolerable monthly intake of 70 pg TEQ kg-1
      bw month-1 set by the Scientific Committee on Food and the Joint FAO/WHO Expert
      Committee on Food, respectively. These results show that the contamination levels
      in food and therefore the exposure of the general population to PCDD/Fs and PCBs
      have declined in this region and therefore show the efficiency of the European
      risk-management measures. In terms of risk characterisation, the results showed
      that, under the upper-bound scenario, 22% of the adult and 58% of the young
      people population could exceed the TWI.

PMID- 29219743
TI  - Building a polysaccharide hydrogel capsule delivery system for control release of
      ibuprofen.
AB  - Development of a delivery system which can effectively carry hydrophobic drugs
      and have pH response is becoming necessary. Here we demonstrate that through
      preparation of beta-cyclodextrin polymer (beta-CDP), a hydrophobic drug molecule
      of ibuprofen (IBU) was incorporated into our prepared beta-CDP inner cavities,
      aiming to improve the poor water solubility of IBU. A core-shell capsule
      structure has been designed for achieving the drug pH targeted and sustained
      release. This delivery system was built with polysaccharide polymer of Sodium
      alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose
      (HEC) by physical cross-linking. The drug pH-response control release is this
      hydrogel system's chief merit, which has potential value for synthesizing enteric
      capsule. Besides, due to our simple preparing strategy, optimal conditions can be
      readily determined and the synthesis process can be accurately controlled,
      leading to consistent and reproducible hydrogel capsules. In addition, phase
      solubility method was used to investigate the solubilization effect of IBU by
      beta-CDP. SEM was used to prove the forming of core and shell structure. FT-IR
      and 1H-NMR were also used to perform structural characteristics. By the technique
      of UV determination, the pH targeted and sustained release study were also
      performed. The results have proved that our prepared polysaccharide hydrogel
      capsule delivery system has potential applications as oral drugs delivery in the
      field of biomedical materials.

PMID- 29219744
TI  - N-nitrosamines migrating from food contact materials into food simulants:
      analysis and quantification by means of HPLC-APCI-MS/MS.
AB  - It was the aim of the work described here to develop a validated analytical
      method for the determination of N-nitrosamines in food simulants. Here, we
      present the validation of a liquid chromatography-atmospheric pressure chemical
      ionisation-tandem mass spectrometry method for the determination of 13 N
      nitrosamines in the food simulants deionised water, 3% acetic acid and 10%
      ethanol. Method validation encompassed linearity, LOD, LOQ, recovery, precision
      and stability of the N-nitrosamines. The method was found to be sufficiently
      rugged and suitable for routine analysis. In addition, the developed method is on
      average 10 times more sensitive than the gas chromatography-thermal energy
      analyser (GC-TEA) method that is currently stipulated in Recommendation XXI for
      commodities based on natural and synthetic rubber issued by the German Federal
      Institute for Risk Assessment (BfR). The developed method was applied to
      determine the N-nitrosamine contents in migration solutions of 12 elastomer
      samples covering a range of different elastomer types. In 10 out of 12 samples, N
      nitrosamines were determined. In most samples, the guidance value of 1 ug/dm2
      specified in BfR Recommendation XXI was not exceeded. In conclusion, the
      analytical method presented here offers a useful alternative to the GC-TEA method
      currently stipulated in BfR Recommendation XXI. This is of wider relevance, since
      BfR recommendations are used for compliance assessment of Article 3, paragraph 1
      a of the Regulation (EC) No. 1935/2004 with respect to their health safety.

PMID- 29219745
TI  - Corrigendum: Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles
      Across the Life Span.
AB  - Original article: Zilioli, S., Slatcher, R. B., Chi, P., Li, X., Zhao, J., &
      Zhao, G. (2016). Childhood adversity, self-esteem, and diurnal cortisol profiles
      across the life span. Psychological Science, 27, 1249-1265.
      doi:10.1177/0956797616658287.

PMID- 29219746
TI  - Development of two surgical approaches to the pituitary gland in the Horse.
AB  - BACKGROUND: Current treatment of equine pituitary pars intermedia dysfunction
      (PPID) requires daily oral medication. Minimally invasive surgical palliation of
      this condition is appealing as a single treatment to alleviate the clinical signs
      of disease, dramatically improving the welfare of the horse. OBJECTIVE: To
      develop a surgical approach to the equine pituitary gland, for subsequent
      treatment of PPID. STUDY DESIGN: A cadaver study to develop methodology and a
      terminal procedure under anaesthesia in the most promising techniques. ANIMALS
      AND METHODS: Four surgical approaches to the pituitary gland were investigated in
      cadaver animals. A ventral trans-basispheniodal osteotomy and a minimally
      invasive intravenous approach via the ventral cavernous sinus progressed to live
      horse trials. RESULTS: Technical complications prevented the myeloscopic and
      trans-sphenopalatine sinus techniques from being successful. The ventral
      basisphenoidal osteotomy was repeatable and has potential if an intra-operative
      imaging guidance system could be employed. The minimally invasive approach was
      repeatable, atraumatic and relatively inexpensive. CONCLUSIONS: A minimally
      invasive surgical approach to the equine pituitary gland is possible and allows
      for needle placement within the target tissue. More work is necessary to
      determine what that treatment might be, but repeatable access to the gland has
      been obtained, which is a promising step.

PMID- 29219747
TI  - Using magnetic materials to harvest microalgal biomass: evaluation of harvesting
      and detachment efficiency.
AB  - Using naked iron oxide (Fe3O4) and yttrium iron oxide (Y3Fe5O12) nanoparticles as
      flocculants, the harvesting efficiency of Chlorella vulgaris biomass was
      investigated. The harvesting process includes two steps, which are the separation
      of microalgae from the culture solution with the magnetic nanoparticles and then
      the separation of the algae from the magnetic nanoparticles. The optimal dosages
      and pH values for the magnetic harvesting of microalgal biomass were determined.
      Results showed that Y3Fe5O12 nanoparticles were more efficient in microalgal
      biomass harvesting than Fe3O4 nanoparticles. In an effort to achieve more than
      90% of harvesting efficiency, optimal dosages for Fe3O4 and Y3Fe5O12 to harvest
      microalgal biomass were 10 and 2.5 g/L, while the appropriate pH values were 6.2
      and 7.3, respectively. The harvesting efficiency of Fe3O4 and Y3Fe5O12
      nanoparticles increased as the pH value decreased. The experimental results also
      showed that under a higher pH value Fe3O4 nanoparticles were much easier to be
      separated from the flocs than Y3Fe5O12. 62.9% of Fe3O4 nanoparticles could be de
      attached from the aggregates, when the floc pH value reached 12.3.

PMID- 29219749
TI  - Moving toward a universally accessible web: Web accessibility and education.
AB  - The World Wide Web is an extremely powerful source of information, inspiration,
      ideas, and opportunities. As such, it has become an integral part of daily life
      for a great majority of people. Yet, for a significant number of others, the
      internet offers only limited value due to the existence of barriers which make
      accessing the Web difficult, if not impossible. This article illustrates some of
      the reasons that achieving equality of access to the online world of education is
      so critical, explores the current status of Web accessibility, discusses
      evaluative tools and methods that can help identify accessibility issues in
      educational websites, and provides practical recommendations and guidelines for
      resolving some of the obstacles that currently hinder the achievability of the
      goal of universal Web access.

PMID- 29219748
TI  - Symmetric Objects Become Special in Perception Because of Generic Computations in
      Neurons.
AB  - Symmetry is a salient visual property: It is easy to detect and influences
      perceptual phenomena from segmentation to recognition. Yet researchers know
      little about its neural basis. Using recordings from single neurons in monkey IT
      cortex, we asked whether symmetry-being an emergent property-induces nonlinear
      interactions between object parts. Remarkably, we found no such deviation: Whole
      object responses were always the sum of responses to the object's parts,
      regardless of symmetry. The only defining characteristic of symmetric objects was
      that they were more distinctive compared with asymmetric objects. This was a
      consequence of neurons preferring the same part across locations within an
      object. Just as mixing diverse paints produces a homogeneous overall color,
      adding heterogeneous parts within an asymmetric object renders it indistinct. In
      contrast, adding identical parts within a symmetric object renders it distinct.
      This distinctiveness systematically predicted human symmetry judgments, and it
      explains many previous observations about symmetry perception. Thus, symmetry
      becomes special in perception despite being driven by generic computations at the
      level of single neurons.

PMID- 29219751
TI  - Patent highlights August-September 2017.
AB  - A snapshot of noteworthy recent developments in the patent literature of
      relevance to pharmaceutical and medical research and development.

PMID- 29219750
TI  - A role for histone acetylation in regulating transcription elongation.
AB  - Recently, we reported that a major function of histone acetylation at the yeast
      FLO1 gene was to regulate transcription elongation. Here, we discuss possible
      mechanisms by which histone acetylation might regulate RNA polymerase II
      processivity, and comment on the contribution to transcription of chromatin
      remodelling at gene coding regions and promoters.

PMID- 29219752
TI  - Negative surgical exploration in patients with Cushing's disease: benefit of two
      thirds gland resection on remission rate and a review of the literature.
AB  - OBJECTIVE The authors report their single-institution experience with the
      pathological findings, rates of remission, and complications in patients with
      presumed Cushing's disease (CD) who underwent a two-thirds pituitary gland
      resection when no adenoma was identified at the time of transsphenoidal surgery
      (TSS). The authors also review the literature on patients with CD, negative
      surgical exploration, and histological findings. METHODS This study is a
      retrospective analysis of cases found in neurosurgery and pathology department
      databases between 1989 and 2011. In all cases, patients had been operated on by
      the same neurosurgeon (K.O.L.). Twenty-two (13.6%) of 161 patients who underwent
      TSS for CD had no adenoma identified intraoperatively after systematic
      exploration of the entire gland; these patients all underwent a two-thirds
      pituitary gland resection. A chart review was performed to assess treatment data
      points as well as clinical and biochemical remission status. RESULTS Of the 22
      patients who underwent two-thirds gland resection, 6 (27.3%) ultimately had
      lesions found on final pathology. All 6 patients were found to have a distinct
      adrenocorticotropic hormone (ACTH) cell adenoma. Sixteen (72.7%) of the patients
      had no tumor identified, with 3 of these patients suspected of having ACTH cell
      hyperplasia. The follow-up duration for the entire group was between 14 and 315
      months (mean 98.9 months, median 77 months). Remission rates were 100% (6/6
      patients) for the ACTH cell adenoma group and 75% (12/16) for the group without
      adenoma. Overall, 18 (81.8%) of the 22 patients had no evidence of
      hypercortisolism at last follow-up, and 4 patients (18%) had persistent
      hypercortisolism, defined as a postoperative cortisol level > 5 MUg/dl. Of these
      4 patients, 1 was suspected of harboring a cavernous sinus adenoma, 2 were found
      to have lung tumors secreting ACTH, and 1 remained with an undiagnosed etiology.
      Rates of postoperative complications were low. CONCLUSIONS The diagnosis and
      treatment of CD can be challenging for neurosurgeons, endocrinologists, and
      pathologists alike. Failure to find a discrete adenoma at the time of surgery
      occurs in at least 10%-15% of cases, even in experienced centers. The current
      literature provides little guidance regarding rational intraoperative approaches
      in such cases. The authors' experience with 161 patients with CD, when no
      intraoperative tumor was localized, demonstrates the utility of a two-thirds
      pituitary gland resection with a novel and effective surgical strategy, as
      suggested by a high initial remission rate and a low operative morbidity.

PMID- 29219753
TI  - Resection of primary motor cortex tumors: feasibility and surgical outcomes.
AB  - OBJECTIVE: Brain tumors involving the primary motor cortex are often deemed
      unresectable due to the potential neurological consequences that result from
      injury to this region. Nevertheless, we have challenged this dogma for many years
      and used asleep, as well as awake, intraoperative stimulation mapping to maximize
      extent of resection. It remains unclear whether these tumors can be resected with
      acceptable morbidity, whether performing the surgery with the patient awake or
      asleep impacts extent of resection, and how stimulation mapping influences
      outcomes. METHODS: A retrospective chart review was performed on the senior
      author's cohort to identify patients treated between 1998 and 2016 who underwent
      resection of tumors that were located within the primary motor cortex. Clinical
      notes, operative reports, and radiographic images were reviewed to identify
      intraoperative stimulation mapping findings and functional outcomes following
      tumor resection. Extent of resection was quantified volumetrically.
      Characteristics of patients were analyzed to identify factors associated with
      postoperative motor deficits. RESULTS: Forty-nine patients underwent 53
      resections of tumors located primarily within the motor cortex. Stimulation
      mapping was performed in all cases. Positive cortical sites for motor response
      were identified in 91% of cases, and subcortical sites in 74%. Awake craniotomy
      was performed in 65% of cases, while 35% were done under general anesthesia. The
      mean extent of resection was 91%. There was no statistically significant
      difference in extent of resection in cases done awake compared with those done
      under general anesthesia. New or worsened postoperative motor deficits occurred
      in 32 patients (60%), and 20 patients (38%) had a permanent deficit. Of the
      permanent deficits, 14 were mild, 4 were moderate, and 2 were severe (3.8% of
      cases). Decreased intraoperative motor response and diffusion restriction on
      postoperative MRI were associated with permanent deficit. Awake motor mapping
      surgery was associated with increased diffusion signal on postoperative MRI.
      CONCLUSIONS: Resection of tumors from the primary motor cortex is associated with
      an increased risk of motor deficit, but most of these deficits are transient or
      mild and have little functional impact. Excellent extent of resection can be
      achieved with intraoperative stimulation mapping, suggesting that these tumors
      are indeed amenable to resection and should not be labeled unresectable. Injury
      to small perforating or en passage blood vessels was the most common cause of
      infarction that led to moderate or severe deficits. Awake motor mapping was not
      superior to mapping done under general anesthesia with regard to long-term
      functional outcome.

PMID- 29219754
TI  - Shunt scissors: technical note.
AB  - OBJECTIVE When performing ventriculoperitoneal shunt surgery it is necessary to
      create a subgaleal pocket that is of sufficient size to accommodate a shunt
      valve. In most cases the valve is placed over the posterior skull where the galea
      begins to transition to suboccipital neck fascia. Dense fibrous attachments in
      this region of the skull make it technically awkward to develop the subgaleal
      valve pocket using standard scissors and a blunt dissection technique. In this
      report the authors describe a new device that enables surgeons to create the
      shunt valve pocket by using a simple semi-sharp dissection technique. METHODS The
      authors analyzed the deficiencies of the standard valve pocket dissection
      technique and designed shunt scissors that address the identified shortcomings.
      These new scissors allow the surgeon to sharply dissect the subgaleal space by
      using an efficient hand-closing maneuver. RESULTS Standard surgical scissors were
      modified to create shunt scissors that were tested on the benchtop and used in
      the operating room. In all cases the shunt scissors proved easy to use and
      allowed the efficient and reliable creation of a subgaleal valve pocket in a
      technically pleasing manner. CONCLUSIONS Shunt scissors represent an incremental
      technical advance in the field of neurosurgical shunt operations.

PMID- 29219755
TI  - Mitochondrial abnormalities related to the dysfunction of circulating endothelial
      colony-forming cells in moyamoya disease.
AB  - OBJECTIVE Moyamoya disease (MMD) is a unique cerebrovascular disorder
      characterized by the progressive occlusion of the bilateral internal carotid
      arteries. Endothelial colony-forming cells (ECFCs), previously termed
      "endothelial progenitor cells," play an important role in the pathogenesis of
      MMD. In this study, the authors performed morphological and functional studies of
      the mitochondria of ECFCs from patients with MMD to present new insights into the
      pathogenesis of the disease. METHODS The morphology of ECFCs from 5 MMD patients
      and 5 healthy controls was examined under both a transmission electron microscope
      and a confocal laser scanning microscope. The oxygen consumption rates (OCRs),
      mitochondrial membrane potentials (MMPs), intracellular Ca2+ concentrations,
      mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were
      measured. Functional activity of the ECFCs was evaluated using a capillary tube
      formation assay. RESULTS The ECFCs from the MMD patients displayed a disrupted
      mitochondrial morphology, including a shorter and more circular shape. The ECFC
      mitochondria from the MMD patients exhibited functional abnormalities, which were
      assessed as a decreased OCR and an increased intracellular Ca2+ concentration.
      Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly,
      treatment with an ROS scavenger not only reversed the mitochondrial abnormalities
      but also restored the angiogenic activity of the ECFCs from the MMD patients.
      CONCLUSIONS The mitochondria of ECFCs from MMD patients, as compared with those
      from healthy patients, exhibited morphological and functional abnormalities. This
      finding suggests that the mitochondrial abnormalities may have a role in the
      pathogenesis of MMD.

PMID- 29219756
TI  - Awake perimetry testing for occipital epilepsy surgery.
AB  - In the literature, there are few reports that provide a detailed account on the
      technique of visual electrocortical stimulation in the setting of resective
      surgery for occipital epilepsy. In this technical note, the authors describe how
      a 26-year-old male with long-standing occipital epilepsy underwent resective
      surgery under awake conditions, using electrocortical stimulation of the
      occipital lobe, with the aid of a laser pointer and a perimetry chart on a stand
      within his visual field. The eloquent primary visual cortex was found to overlap
      with the seizure onset zone that was previously determined with subdural
      electrodes. A maximum functionally safe resection was performed, rendering the
      patient seizure free as of his last follow-up at 20 months, with no visual field
      impairment.

PMID- 29219757
TI  - Spinal accessory nerve to triceps muscle transfer using long autologous nerve
      grafts for recovery of elbow extension in traumatic brachial plexus injuries.
AB  - Despite continuous improvement and expansion of reconstructive options for
      traumatic brachial plexus injury, options to reinnervate the triceps muscle
      remain somewhat sparse. This study describes a novel option, using a spinal
      accessory nerve transfer to the long head of the triceps muscle with an
      intervening autologous nerve graft. The resulting quality of elbow extension and
      factors that influence outcome are discussed.

PMID- 29219758
TI  - The use of alternatives to clopidogrel in flow-diversion treatment with the
      Pipeline embolization device.
AB  - OBJECTIVE Thromboembolic complications continue to be encountered with Pipeline
      embolization devices (PEDs) despite routine clopidogrel/aspirin antiplatelet
      therapy. This study examined the safety and efficacy of prasugrel in the
      management of clopidogrel-resistant patients treated for cerebral aneurysms.
      METHODS Four hundred thirty-seven consecutive patients were identified between
      January 2011 and May 2016. Patients allergic, or having less than 30% platelet
      inhibition, to a daily 75-mg dose of clopidogrel received 10 mg of prasugrel
      daily (n = 20) or 90 mg of ticagrelor twice daily (n = 2). The mean (+/- SD)
      follow-up duration was 15.8 +/- 12.4 months. The primary outcome was the modified
      Rankin Scale (mRS) score registered before discharge and at each follow-up visit.
      To control confounding, multivariable mixed-effects logistic regression and
      propensity score conditioning were used. RESULTS Twenty-six (5.9%) of 437
      patients presented with a subarachnoid hemorrhage (SAH). The mean patient age was
      56.3 years, and 62 were women (14.2%). One of the 7 patients lost to follow-up
      received prasugrel. One patient was allergic to clopidogrel and prasugrel
      simultaneously. All patients receiving prasugrel or ticagrelor (n = 22) had an
      mRS score <= 2 on their latest follow-up visit (mean score 0.67 +/- 1.15). In a
      multivariate analysis, clopidogrel did not affect the mRS score on last follow-up
      (p = 0.14). Multivariable logistic regression showed that clopidogrel was not
      associated with an increased long-term recurrence rate (OR 0.17, 95% CI 0.01
      2.70, p = 0.21), an increased thromboembolic complication rate (OR 0.46, 95% CI
      0.12-1.67, p = 0.24), or an increased hemorrhagic event rate (OR 0.39, 95% CI
      0.91-1.64, p = 0.20). None of the patients receiving prasugrel or ticagrelor died
      or suffered a long-term recurrence or a hemorrhagic event; only 1 patient
      suffered from mild aphasia subsequent to a thromboembolic event. Three patients
      taking clopidogrel died during the study: 2 from acute SAH and 1 from
      intraparenchymal hemorrhage. Clopidogrel was not associated with an increased
      mortality rate (OR 2.18, 95% CI 0.11-43.27, p = 0.61). The same associations were
      present in propensity score-adjusted models. CONCLUSIONS In a cohort of patients
      treated with PEDs, prasugrel (10 mg/day) was a safe alternative to clopidogrel
      resistant or clopidogrel-allergic patients, or nonresponders.

PMID- 29219759
TI  - Does the obesity paradox predict functional outcome in intracerebral hemorrhage?
AB  - OBJECTIVE Being overweight or mildly obese has been associated with a decreased
      risk of death or hospitalization in patients with cardiovascular disease.
      Similarly, overweight patients admitted to an intensive care unit (ICU) have
      improved survival up to 1 year after admission. These counterintuitive
      observations are examples of the "obesity paradox." Does the obesity paradox
      exist in patients with intracerebral hemorrhage (ICH)? In this study the authors
      examined whether there was an association between obesity and functional outcome
      in patients with ICH. METHODS The authors analyzed 202 patients admitted to the
      neurological ICU (NICU) who were prospectively enrolled in the Columbia
      University ICH Outcomes Project between September 2009 and December 2012.
      Patients were categorized into 2 groups: overweight (body mass index [BMI] >= 25
      kg/m2) and not overweight (BMI < 25 kg/m2). The primary outcome was defined as
      survival with favorable outcome (modified Rankin Scale [mRS] score 0-3) versus
      death or severe disability (mRS score 4-6) at 3 months. RESULTS The mean age of
      the patients in the study was 61 years. The mean BMI was 28 +/- 6 kg/m2. The mean
      Glasgow Coma Scale score was 10 +/- 4 and the mean ICH score was 1.9 +/- 1.3. The
      overall 90-day mortality rate was 41%. Among patients with a BMI < 25 kg/m2, 24%
      (17/70) had a good outcome, compared with 39% (52/132) among those with a BMI >=
      25 kg/m2 (p = 0.03). After adjusting for ICH score, sex, do-not-resuscitate code
      status, and history of hypertension, being overweight or obese (BMI >= 25 kg/m2)
      was associated with twice the odds of having a good outcome compared with
      patients with BMI < 25 kg/m2 (adjusted odds ratio 2.05, 95% confidence interval
      1.03-4.06, p = 0.04). CONCLUSIONS In patients with ICH admitted to the NICU,
      being overweight or obese (BMI >= 25 kg/m2) was associated with favorable outcome
      after adjustment for established predictors. The reason for this finding requires
      further study.

PMID- 29219760
TI  - Direct visualization of microcirculation impairment after acute subdural
      hemorrhage in a novel animal model.
AB  - OBJECTIVE: Direct brain compression and secondary injury due to increased
      intracranial pressure are believed to be the pathognomic causes of a grave
      outcome in acute subdural hemorrhage (aSDH). However, ischemic damage from aSDH
      has received limited attention. The authors hypothesized that cerebral
      microcirculation is altered after aSDH. Direct visualization of microcirculation
      was conducted in a novel rat model. METHODS: A craniectomy was performed on each
      of the 18 experimental adult Wistar rats, followed by superfusion of autologous
      arterial blood onto the cortical surface. Changes in microcirculation were
      recorded by capillary videoscopy. Blood flow and the partial pressure of oxygen
      in the brain tissue (PbtO2) were measured at various depths from the cortex. The
      brain was then sectioned for pathological examination. The effects of aspirin
      pretreatment were also examined. RESULTS: Instantaneous vasospasm of small
      cortical arteries after aSDH was observed; thrombosis also developed 120 minutes
      after aSDH. Reductions in blood flow and PbtO2 were found at depths of 2-4 mm.
      Blood-brain barrier disruption and thrombi formation were confirmed using
      immunohistochemical staining, while aspirin pretreatment reduced thrombosis and
      the impairment of microcirculation. CONCLUSIONS: Microcirculation impairment was
      demonstrated in this aSDH model. Aspirin pretreatment prevented the diffuse
      thrombosis of cortical and subcortical vessels after aSDH.

PMID- 29219761
TI  - The fate of nitrite and nitrate during anaerobic digestion.
AB  - Anaerobic digestion is widely used to produce renewable energy. However, the main
      drawback is the limited conversion efficiency of organic matter. Applying an
      advanced oxidation process as a digestate post-treatment is able to increase this
      conversion efficiency but will also lead to the oxidation of ammonium to nitrite
      or nitrate. In this lab-scale study, the fate of the latter in the digester was
      investigated. Nitrite and nitrate were therefore added in concentrations that
      could arise from rate-limiting ammonium concentrations (1.25-5 g L-1 N). The
      study clearly demonstrated that nitrite and nitrate were denitrified during the
      subsequent digestion process resulting in the formation of nitrogen gas. After a
      concentration-dependent adaptation period, in which some biogas was produced, the
      added nitrite was denitrified in amounts proportional to the amounts of electron
      donor present. This denitrification, however, strongly reduces the possibility
      that Anammox bacteria can develop. Nitrate was also denitrified in amounts
      proportional to the amounts of electron donor, but biogas production was not
      completely blocked in this case. Moreover, high concentrations of nitrite and
      nitrate inhibited their own denitrification. The methane formed was used as
      electron donor for the further denitrification of nitrate and nitrite when no
      other readily available electron donor was present. After addition of either
      nitrite or nitrate and their denitrification, the biogas production did not
      recover properly.

PMID- 29219762
TI  - Establishing the critical role of peripheral blood vessel colonisation by
      Neisseria meningitidis in invasive meningococcal disease.
AB  - In this issue of Virulence, Capel and colleagues describe the use of a unique
      humanised mouse model to elucidate specific interactions between Neisseria
      meningitidis and human endothelial cells during blood-borne infection in vivo.
      Here, a number of the key findings from their study and their implications for
      our understanding of invasive meningococcal disease are explored.

PMID- 29219763
TI  - Reviews.

PMID- 29219765
TI  - Forthcoming events.

PMID- 29219535
TI  - Search for Dark Matter Produced in Association with a Higgs Boson Decaying to
      bb[over -] Using 36  fb^{-1} of pp Collisions at sqrt[s]=13  TeV with the ATLAS
      Detector.
AB  - Several extensions of the standard model predict associated production of dark
      matter particles with a Higgs boson. Such processes are searched for in final
      states with missing transverse momentum and a Higgs boson decaying to a bb[over 
      ] pair with the ATLAS detector using 36.1  fb^{-1} of pp collisions at a center
      of-mass energy of 13 TeV at the LHC. The observed data are in agreement with the
      standard model predictions and limits are placed on the associated production of
      dark-matter particles and a Higgs boson.

PMID- 29219767
TI  - Hirsutism and virilization.
AB  - Preview The appearance of unwanted body hair in a woman is often the result of a
      benign condition requiring medical and cosmetic therapy only. However, sometimes,
      especially when accompanied by features of virilization, hirsutism signals an
      ovarian or adrenal tumor. The authors define the broad categories of causes and
      review treatment options, from weight loss to surgical intervention.

PMID- 29219766
TI  - Development and validation of multi-residue and multi-class method for
      antibacterial substances analysis in non-target feed by liquid chromatography -
      tandem mass spectrometry.
AB  - A confirmatory HPLC-MS/MS method for the determination of residues of 11
      antibacterial substances from different therapeutic class (beta-lactams,
      lincosamides, fluoroquinolones, macrolides, pleuromutilins and sulfonamides) in
      animal feeds has been developed. The sample preparation is based on extraction
      with 0.1% formic acid in acetonitrile. Separation of the analytes was performed
      on biphenyl column with a gradient of 0.1% formic acid in acetonitrile and 0.1%
      formic acid in Milli-Q water. The developed method was validated following the
      guidelines included in the European Union Commission Decision 2002/657/EC. Limits
      of detection ranging from 79.22 to 193.60 ug/kg; instrumental and analytical
      linearity coefficients were above 0.99 for matrix-match calibration; and relative
      recoveries ranging from 76.04% to 117.39%. Repeatability of the method was in the
      range of 2.41-19.76% (CV, %), whereas reproducibility ranged from 6.52 to 28.40%
      (CV %). The method shown to be efficient and precise for quantification of the 11
      antibacterial substances in animal feed. The results demonstrate the feasibility
      of the method for routine use to monitor these substances in feed. The validated
      method was successfully applied to eight suspect feed samples collected from the
      Association of American Feed Control Officials (AFFCO) and feed manufactures from
      Galicia (Spain) in June and July 2017. Of these 8 non-target feeds, 5 were
      positive for the presence of tiamulin, tylosin and sulfadiazine.

PMID- 29219768
TI  - Institutional placement for patients with Alzheimer's disease.
AB  - Preview Families of patients with Alzheimer's disease often want guidance from
      the patient's physician on whether to put the patient in an institution. When is
      institutional placement indicated? What types of facilities are available? What
      should family members took for in a facility before and after placement? Dr
      Pfeiffer provides the answers to these and other questions raised by families
      facing this difficult decision.

PMID- 29219773
TI  - Polymyalgia rheumatica or Lyme disease?
AB  - Preview The presentation of Lyme disease may resemble that of polymyalgia
      rheumatica. What's more, the latter may occur in patients who have positive
      serologic findings for the former. In this case report, the author describes
      differential diagnosis in an elderly patient whose rheumatic complaints and blood
      chemistry profile alone could easily have led to misdiagnosis. Important points
      in evaluation and treatment are discussed.

PMID- 29219772
TI  - Venous thrombosis.
AB  - Preview The list of recognized risk factors for deep venous thrombosis and
      pulmonary embolism is formidable. Classic findings of edema, warmth, erythema,
      and tenderness are often absent. A clinical impression of deep venous thrombosis
      is correct only 50% of the time and must be confirmed with imaging studies.
      Management includes thrombolysis, surgical thrombectomy and, in some cases,
      lifelong use of anticoagulants.

PMID- 29219775
TI  - Acute pulmonary embolism.
AB  - Preview According to the authors, acute pulmonary embolism can never be
      considered clinically insignificant. Many patients die before reaching medical
      help, but appropriate therapy for those who survive may greatly reduce the
      potential for sudden death and long-term morbidity. This article describes the
      proper steps in the management of both stable and unstable acute pulmonary
      embolism.

PMID- 29219777
TI  - Carpal tunnel syndrome.
AB  - Preview Data entry, bar-code scanning at a grocery store checkout, playing the
      drums-these are all activities that may precipitate carpal tunnel syndrome, the
      most common entrapment neuropathy. Beyond cessation of repetitive wrist motions,
      treatment options range from corticosteroid injection to surgical intervention.
      Which form of therapy is best for your patient? Which tests are most useful in
      clinical evaluation? The authors address these questions in this overview of
      diagnosis and treatment.

PMID- 29219778
TI  - Chronic pulmonary embolism.
AB  - Preview Patients with chronic thromboembolic pulmonary hypertension have
      nonspecific complaints, and their disease is often not recognized until it is far
      advanced. Because medical management does not reverse the effects of the disease
      or prevent progression, pulmonary endarterectomy by an experienced surgical team
      is currently the preferred treatment. However, the risks of surgery are
      substantial and must be weighed against the probable benefit.

PMID- 29219770
TI  - Hypercalcemia.
AB  - Preview An elevated serum calcium level requires thorough investigation. Is
      hyperparathyroidism at the root of the abnormality? Malignant disease? Vitamin
      toxicity? In this article, Dr Kaye discusses clinical evaluation of hypercalcemia
      and outlines pharmacologic therapy, surgical intervention, and other treatment
      options that help to restore normocalcemia.

PMID- 29219769
TI  - Cytomegalovirus retinitis in persons with AIDS.
AB  - Preview Almost one third of persons with AIDS acquire retinitis caused by the
      opportunistic cytomegalovirus (CMV). Both ganciclovir and foscamet have been
      approved for treatment of CMV retinitis and are equally effective. However, their
      side effects are not the same, and each may have a different impact on the
      overall course of HIV infection and AIDS. The drug chosen should be administered
      promptly when sight-threatening disease is diagnosed to ensure maximal vision for
      the longest time.

PMID- 29219774
TI  - Checks that Bounce.

PMID- 29219771
TI  - Otitis media with effusion in infants and children.
AB  - Preview A crabby infant or a toddler pulling at his or her ears is a fairly
      common sight in a primary care office, and a 10-day course of antibiotics often
      does the trick. But what should you do when this doesn't work? And what if
      symptoms seem to resolve but effusion continues? The authors describe acute and
      chronic otitis media, explain how to diagnose and treat patients to avoid
      lifelong problems, and suggest when to call in an otolaryngologist.

PMID- 29219776
TI  - Suspected pulmonary embolism.
AB  - Preview Pulmonary embolism, a common complication off deep venous thrombosis that
      may cause sudden death or chronic disability is notoriously difficult to
      diagnose. It may be silent, or it may mimic precisely the typical presentation of
      numerous other diseases. In this article, the authors describe the classic signs
      and symptoms and discuss current procedures that must be used in evaluation. They
      also provide a work sheet to aid physicians in the clinical application of
      ventilation-perfusion scan results.

PMID- 29219779
TI  - Metastases of spinal myxopapillary ependymoma: unique characteristics and
      clinical management.
AB  - OBJECTIVE Myxopapillary ependymoma is a benign WHO Grade I tumor most commonly
      located in the conus-cauda equina region of the spine. Although this tumor is
      defined by an overall excellent survival, dissemination throughout the whole
      neuraxis occurs frequently. The current study evaluated the clinical
      characteristics and significance of myxopapillary ependymoma metastases. METHODS
      Patients who underwent surgery from 2005 to 2015 for treatment of spinal
      myxopapillary ependymoma were included in the study. Charts were reviewed for
      primary tumor symptoms and initial treatment, local recurrence, response to
      salvage therapy, and presence and behavior of distant metastases. RESULTS
      Nineteen patients with spinal myxopapillary ependymoma were included in the study
      (52.6% female). The median age at first diagnosis was 32 years old (range 9-58
      years old), and 26.3% were <= 18 years old. The median follow-up of all included
      patients was 48 months (range 6-456 months). Of the primary tumors, 84.2% were
      located in the lower thoracic or upper lumbar spine, spanning 1-3 levels in
      94.7%. All patients underwent surgery for initial treatment: in 78.9% a gross
      total resection (GTR) was achieved, with adjuvant radiation therapy (RT) in 20%.
      Of the 21.2% who underwent a subtotal resection (STR), 75% underwent
      postoperative RT. Tumor progression was noted in 26.3% of patients after a median
      36-month follow-up (range 12-240 months). In 57.9% of patients, distant
      metastases were found, of which 36.4% were present at initial diagnosis. Further
      metastases occurred within a median of 20 months (range 2-360 months). Following
      a diagnosis of metastatic tumor, 72.7% did not show progression and no symptoms
      were observed during a median follow-up of 36 months (range 6-216 months).
      Metastases occurred in all parts of the neuroaxis, but were principally localized
      in the thoracic and sacral spine in 38.9% and 33.3%, respectively; the brain was
      involved in 11.1%. In 54.5%, more than 1 level was affected. Overall survival was
      100% with an excellent clinical and neurological outcome in 78.9% of cases.
      CONCLUSIONS Metastatic dissemination within the CNS can be observed in many
      patients with myxopapillary ependymoma. GTR of the primary tumor should be the
      primary treatment goal, and additional RT is recommended after STR. For distant
      metastases of myxopapillary ependymoma without clinical manifestation, close
      clinical and MRI follow-up represents a sufficient strategy because most of the
      metastases remain asymptomatic and do not show progression over time. Additional
      resection or irradiation as salvage therapy would be recommended if metastases
      become symptomatic.

PMID- 29219780
TI  - Anatomical and technical factors associated with superior facet joint violation
      in lumbar fusion.
AB  - OBJECTIVE The aim of this study was to evaluate the anatomical and surgical risk
      factors for screw-related facet joint violation at the superior level in lumbar
      fusion. METHODS The authors conducted a retrospective review of a consecutive
      series of posterior lumbar instrumented fusions performed by a single surgeon.
      Inclusion criteria were primary lumbar fusion of 1 or 2 levels for degenerative
      disorders. The following variables were analyzed as possible risk factors:
      surgical technique (percutaneous vs open screw placement), depth of surgical
      field, degree of anterior slippage of the superior level, pedicle and facet
      angle, and facet degeneration of the superior level. Postoperative CT scans were
      evaluated by 2 independent reviewers. Axial, sagittal, and coronal views were
      reviewed. Pedicle screws were graded as intra-articular if they clearly
      interposed between the superior and inferior facet joints of the superior level.
      Multivariate logistic regression analyses were conducted to assess the factors
      associated with this complication. RESULTS One hundred thirty-one patients were
      included. Interobserver reliability for facet joint violation assessment was high
      (kappa = 0.789). The incidence of superior facet joint violation was 12.59% per
      top-level screw (33 of 262 proximal screws). The rate of facet violation was
      28.0% in the percutaneous technique group (14 of 50 patients) and 12.3% in the
      open surgery group (10 of 81 patients) (OR 2.26, 95% CI 1.09-4.21; p = 0.024). In
      multivariate logistic regression analysis, independent predictors of facet
      violation were percutaneous screw placement (adjusted OR 3.31, 95% CI 1.42-7.73;
      p = 0.006), right-side pedicle screw (adjusted OR 3.14, 95% CI 1.29-7.63; p =
      0.011), and facet angle > 45 degrees  (adjusted OR 10.95, 95% CI 4.64-25.84; p <
      0.0001). CONCLUSIONS The incidence of facet joint violation was higher in
      percutaneous minimally invasive than in open technique for posterior lumbar spine
      surgery. Also, coronal orientation of the facet joint is a significant risk
      factor independent of the surgical technique.

PMID- 29219781
TI  - A novel duraplasty technique following fenestration of a massive lumbar arachnoid
      cyst in a patient with scoliosis: technical case report.
AB  - When a dural defect is encountered during spine surgery, the dura mater must be
      reconstituted to minimize the occurrence of minor or major life-threatening
      sequelae. The neurosurgical literature lacks strategies for managing large dural
      defects encountered during surgery. The authors describe a 24-year-old man who
      developed cauda equina syndrome secondary to altered CSF flow in a large
      thoracolumbar arachnoid cyst. Surgical decompression and fenestration of the
      arachnoid cyst were performed, and the large dural defect was treated using a
      multilayer closure with collagen matrix, titanium mesh, and methylmethacrylate.
      At his 24-month postoperative follow-up, the patient had recovered full strength
      in his legs, and his sensory deficits and sexual dysfunction had resolved. His
      incision had healed well, and there were no signs of pseudomeningocele. He had no
      additional positional headaches. The defect was managed effectively with this
      technique. Although this technique is not a first-line strategy for dural closure
      in the spine, it can be considered in challenging cases when large dural defects
      are not amenable to traditional closure techniques.

PMID- 29219782
TI  - Preventive Role of Vitamin D in Silica-Induced Skin Fibrosis: A Study in Relation
      to Oxidative Stress and Pro-Inflammatory Cytokines.
AB  - The protective effects of vitamin D analogue calcipotriol in silica-induced skin
      fibrosis were studied in the present study. Male BALB / c mice were divided into
      four groups; Control, Vitamin D, Silica and Silica+Vitamin D. Silica was
      administered as a single intradermal injection (40 ug / uL, dissolved in normal
      saline; particle size 1 - 5 um) in the hind limbs of animals in Silica &
      Silica+Vitamin D group. Vitamin D group animals received topical application of
      100uL of vitamin D solution (10-7M in Ethanol) daily for 12 weeks. Silica+Vitamin
      D group animals received co-treatment of silica and vitamin D as described for
      other groups. After 12 weeks of treatment, dermal thickness and hydroxyproline
      content of treated sections were measured. The TNF-alpha and IL-6 levels were
      measured in serum of all treated animals. The silica-induced oxidative stress was
      measured in terms of lipid peroxidation in skin tissue. Antioxidant defence
      system was assessed in terms of levels of reduced glutathione, superoxide
      dismutase, catalase, glutathione peroxidase and glutathione reductase. A
      significant increase in the dermal thickness and hydroxyproline content was
      observed after silica treatment (931 +/- 57.98 to 1804.61 +/- 146.20 um)(p <
      0.05). Vitamin D co-treatment reduced dermal thickness and hydroxyproline content
      compared to Silica group (p < 0.05). Similarly a decrease in TNF-alpha and IL-6
      levels were also observed after vitamin D treatment. A significant reduction in
      oxidative stress in terms of lipid peroxidation (4.92 +/- 0.70 to 2.40 +/- 0.31
      nmol / mg protein). Therefore, present study suggested that vitamin D could be an
      effective agent against silica-induced skin fibrosis and oxidative stress.

PMID- 29219783
TI  - Diet and Other Lifestyle Factors Associated with Prostate Cancer Differ Between
      the German and Italian Region of Switzerland.
AB  - PURPOSE: In Switzerland, prostate cancer mortality is higher in the German than
      in the Italian-speaking region. We aimed at exploring the association of living
      in one of the two regions with lifestyle factors presumably lowering the risk of
      prostate cancer. METHODS: We pooled data from the Swiss Health Survey, conducted
      every 5 years 1992 - 2012. Information on diet (meat, fish, dairy, fruits and
      vegetables), alcohol, smoking, physical activity and body mass index were
      dichotomized into "risky" and "risk-reducing" lifestyle behaviour with respect to
      prostate cancer. Multivariable logistic regression analyses were performed to
      assess associations between the German and Italian region of Switzerland and each
      single lifestyle factor. RESULTS: Living in the Italian region was associated
      with "risk-reducing" diet, i.e. with a higher prevalence of low dairy products
      and meat consumption and high fish consumption (odds ratio [OR] 1.34, 95%
      confidence interval [CI] 1.21 - 1.48; OR 3.31, 95% CI 2.94 - 3.72; OR 1.90, 95%
      CI 1.71 - 2.12, respectively). However, men in the Italian region were less
      likely to have low alcohol consumption and regular physical activity than men in
      the German region (OR 0.43, 95% CI 0.36 - 0.52 and OR 0.77, 95% CI 0.69 - 0.86,
      respectively). CONCLUSIONS: Prostate cancer risk-reducing dietary behaviour
      (i.e., less dairy products, less meat and more fish) was more common in the
      Italian region, whereas other risk-reducing lifestyle behaviours were more common
      in the German region.

PMID- 29219784
TI  - The Association Between Cartenoid Status and Body Composition in Children 2 - 18
      Years of Age - A Systematic Review.
AB  - The aim of this review was to determine the association between carotenoid status
      and body composition in children 2 - 18 years of age. Obesity is often related to
      poor dietary habits and lower fruit and vegetable consumption in children. Fruit
      and vegetables are the primary sources of antioxidant-rich dietary carotenoids;
      decreased intake may lead to increased risk of chronic diseases. Identifying
      those with lower carotenoid status in childhood could be an important target for
      public health intervention. Research methods for the review were conducted using
      the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
      checklist and the Central Michigan University library, via multiple scientific
      databases. Medical Subject Heading (MeSH) terms were utilized to identify
      relevant studies for inclusion. Twenty-three studies were included in the review
      (n = 16,285). Thirteen studies reported a significant inverse association between
      carotenoid status and body composition in children (p < 0.05), (n = 15,206). Five
      additional studies had varying associations between body composition and
      carotenoid status based on the type of carotenoid and/or measure of carotenoid
      status (n = 763). Carotenoid status is inversely associated with body
      composition; however, varying degrees of association were observed in this
      review. It remains to be determined whether this association is related to
      intake, fat mass or a combination of the two.

PMID- 29219785
TI  - Higher Absorption of Vitamin C from Food than from Supplements by Breastfeeding
      Mothers at Early Stages of Lactation.
AB  - The aim of the present study was to determine the effect of vitamin C supply in
      the diet of lactating women on vitamin C concentrations in human milk (n = 97)
      sampled at different stages of lactation. Vitamin C levels were measured by
      liquid chromatography. Dietary intake of vitamin C was determined based on 3-day
      food dairies kept by breastfeeding mothers. Maternal dietary intakes of vitamin C
      from natural sources on lactation day 90 (n = 18) were significantly higher than
      on lactation days 15 (n = 42) and 30 (n = 37). The number of women taking vitamin
      C supplements decreased in successive stages of lactation. The average daily
      intake of vitamin C was estimated at 119 mg, but nearly 20% of mothers consumed
      less than 50 mg of vitamin C per day. No significant correlations were observed
      between lactation stage and vitamin C levels in breast milk (r = 0.110, p =
      0.064). The average vitamin C concentrations in human breast milk were determined
      at 50.9 mg / L, and were not higher than 80.6 mg / L regardless of lactation
      stage and maternal intake of vitamin C. Vitamin C excretion into breast milk is
      regulated to prevent exceeding saturation level. The vitamin C concentration in
      milk was positive correlated with maternal intake of vitamin C from food, in the
      case of non-supplemented diet (r = 0.402, p = 0.041). Our results suggest that
      vitamin C occurring in food is much better absorbed and passes into breast milk
      than vitamin C from supplements.

PMID- 29219786
TI  - Periinsular anterior quadrantotomy: technical note.
AB  - Refractory frontal lobe epilepsy has been traditionally treated through a frontal
      lobectomy. A disconnective technique may allow similar seizure outcomes while
      avoiding the complications associated with large brain resections. The aim of
      this study was to describe a new technique of selective disconnection of the
      frontal lobe that can be performed in cases of refractory epilepsy due to
      epileptogenic foci involving 1 frontal lobe (anterior to the motor cortex), with
      preservation of motor function. In addition to the description of the technique,
      an illustrative case is also presented. This disconnective procedure is divided
      into 4 steps: the suprainsular window, the anterior callosotomy, the intrafrontal
      disconnection, and the frontobasal disconnection. The functional neuroanatomy is
      analyzed in detail for each step of the surgery. It is important to perform
      cortical and subcortical electrophysiological mapping to guide this disconnective
      procedure and identify eloquent cortices and intact neural pathways. The authors
      describe the case of a 9-year-old boy who presented with refractory epilepsy due
      to epileptogenic foci localized to the right frontal lobe. MRI confirmed the
      presence of a focal cortical dysplasia of the right frontal lobe. A periinsular
      anterior quadrant disconnection (quadrantotomy) was performed. The postoperative
      period was uneventful, and the patient was in Engel seizure outcome Class I at
      the 3-year follow-up. A significant cognitive gain was observed during follow-up.
      Periinsular anterior quadrantotomy may thus represent a safe technique to
      efficiently treat refractory epilepsy when epileptogenic foci are localized to 1
      frontal lobe while preserving residual motor functions.

PMID- 29219787
TI  - Modification of the BioMedicus centrifugal pump to provide continuous irrigation
      for neuroendoscopy: technical note.
AB  - Continuous irrigation is an important adjunct for successful intraventricular
      endoscopy, particularly for complex cases. It allows better visualization by
      washing out blood and debris, improves navigation by expanding the ventricles,
      and assists with tissue dissection. A method of irrigation delivery using a
      centrifugal pump designed originally for cardiac surgery is presented. The
      BioMedicus centrifugal pump has the desirable ability to deliver a continuous
      laminar flow of fluid that excludes air from the system. A series of
      modifications to the pump tubing was performed to adapt it to neuroendoscopy.
      Equipment testing determined flow and pressure responses at various settings and
      simulated clinical conditions. The pump was then studied clinically in 11
      endoscopy cases and eventually used in 310 surgical cases. Modifications of the
      pump tubing allowed for integration with different endoscopy systems. Constant
      flow rates were achieved with and without surgical instruments through the
      working ports. Optimal flow rates ranged between 30 and 100 ml/min depending on
      endoscope size. Intraoperative use was well tolerated with no permanent morbidity
      and showed consistent flow rates, minimal air accumulation, and seamless
      irrigation bag replacement during prolonged surgery. Although the pump is
      equipped with an internal safety mechanism to protect against pressure buildup
      when outflow obstructions occur, equipment testing revealed that flow cessation
      is not instantaneous enough to protect against sudden intracranial pressure
      elevation. A commonly available cardiac pump system was modified to provide
      continuous irrigation for intraventricular endoscopy. The system alleviates the
      problems of inconsistent flow rates, air in the irrigation lines, and delays in
      changing irrigation bags, thereby optimizing patient safety and surgical
      efficiency. Safe use of the pump requires good ventricular outflow and, clearly,
      sound surgical judgment.

PMID- 29219788
TI  - Differential patterns of metastatic dissemination across medulloblastoma
      subgroups.
AB  - OBJECTIVE Metastatic dissemination is a major treatment challenge and cause of
      death in patients with medulloblastoma. However, the influence of molecular
      biology on the pattern of metastatic dissemination at diagnosis is not known. In
      this study, the authors sought to define the location, pattern, and imaging
      characteristics of medulloblastoma metastases across subgroups at diagnosis.
      METHODS A consecutive cohort of patients with metastatic medulloblastoma at The
      Hospital for Sick Children and the University Hospital Motol, who underwent up
      front MRI of the craniospinal axis, was assembled and allocated to subgroups
      using NanoString limited gene-expression profiling. Radiological characteristics
      (including location, morphology, size, diffusion restriction, and contrast
      enhancement) were discerned through a retrospective review. RESULTS Forty
      metastatic medulloblastomas were identified with up-front neuroimaging of the
      craniospinal axis: 5 sonic hedgehog (SHH), 16 Group 3, and 19 Group 4 metastases.
      Significant subgroup-specific differences were observed, particularly with
      respect to tumor location, size, and morphology. Group 3 metastases were most
      frequently laminar compared with a more nodular pattern in Group 4 (14 of 16 in
      Group 3 vs 8 of 19 in Group 4; p = 0.0004). Laminar metastases were not observed
      in patients with SHH medulloblastoma. Suprasellar metastases are highly specific
      to Group 4 (p = 0.016). Two of the 5 SHH cases had multifocal lesions in the
      cerebellum, raising the possibility that these were in fact synchronous primary
      tumors and not true metastases. A minority of patients with Group 4 metastases
      harbored metastatic deposits that did not enhance on MRI after contrast
      administration, often in patients whose primary tumor did not enhance.
      CONCLUSIONS The location, morphology, and imaging characteristics of metastatic
      medulloblastoma differ across molecular subgroups, with implications for
      diagnosis and management. This suggests that the biology of leptomeningeal
      dissemination differs among medulloblastoma subgroups.

PMID- 29219789
TI  - Oberlin transfer compared with nerve grafting for improving early supination in
      neonatal brachial plexus palsy.
AB  - OBJECTIVE The use of nerve transfers versus nerve grafting for neonatal brachial
      plexus palsy (NBPP) remains controversial. In adult brachial plexus injury,
      transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve
      (Oberlin transfer) is reportedly superior to nerve grafting for restoration of
      elbow flexion. In pediatric patients with NBPP, recovery of elbow flexion and
      forearm supination is an indicator of resolved NBPP. Currently, limited evidence
      exists of outcomes for flexion and supination when comparing nerve transfer and
      nerve grafting for NBPP. Therefore, the authors compared 1-year postoperative
      outcomes for infants with NBPP who underwent Oberlin transfer versus nerve
      grafting. METHODS This retrospective cohort study reviewed patients with NBPP who
      underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single
      institution between 2005 and 2015. A single surgeon conducted intraoperative
      exploration of the brachial plexus and determined the surgical nerve
      reconstruction strategy undertaken. Active range of motion was evaluated
      preoperatively and postoperatively at 1 year. RESULTS No significant difference
      between treatment groups was observed with respect to the mean change (pre- to
      postoperatively) in elbow flexion in adduction and abduction and biceps strength.
      The Oberlin transfer group gained significantly more supination (100 degrees  vs
      19 degrees ; p < 0.0001). Forearm pronation was maintained at 90 degrees  in the
      Oberlin transfer group whereas it was slightly improved in the grafting group (0
      degrees  vs 32 degrees ; p = 0.02). Shoulder, wrist, and hand functions were
      comparable between treatment groups. CONCLUSIONS The preliminary data from this
      study demonstrate that the Oberlin transfer confers an advantageous early
      recovery of forearm supination over grafting, with equivalent elbow flexion
      recovery. Further studies that monitor real-world arm usage will provide more
      insight into the most appropriate surgical strategy for NBPP.

PMID- 29219790
TI  - Hepatitis C Virus Infection in Kidney Transplant Patients: Current Treatment
      Options.
AB  - Hepatitis C virus infection is highly prevalent among kidney transplant
      recipients, occurring consequently to their previous treatment with hemodialysis.
      Hepatitis C virus infection has been associated with lower graft and patient
      survival compared with that shown in patients without infection. The lower
      survival has been associated with the posttransplant progression of liver disease
      and increased risk for development of extrahepatic complications. The choice of
      immunosuppressive drugs could significantly affect the course of the infection
      with an accelerated viral replication after kidney transplant. Eradicating
      hepatitis C virus infection with antiviral treatment is imperative to increasing
      graft and patient survival after transplant. Antiviral treatment options include
      standard interferon-based therapy and new directacting antiviral agents.
      Interferon-based treatment is rarely used in kidney transplant recipients because
      it has been associated with high risk of interferoninduced acute graft rejection.
      Several novel studies have shown that the new direct-acting antiviral agents are
      highly efficacious for treatment of hepatitis C infection in kidney transplant
      patients.

PMID- 29219791
TI  - Effects of the Vitamin D Analog 2AMD in Cyclosporine-Induced Nephrotoxicity: Dose
      Response and Antifibrotic Activity.
AB  - OBJECTIVES: In this study, we aimed to ascertain the efficacy and determine the
      dose effects of a new analog of vitamin D, 2alpha-methyl-19-nor-(20S)-1alpha,25
      dihydroxyvitamin D3 (2AMD), in decreasing fibrosis and improving renal function
      in a rat model of kidney disease. MATERIALS AND METHODS: Using the cyclosporine
      model of chronic kidney disease, we tested 4 dose regimens (2.5, 5, 10, and 20
      ng/kg) of 2AMD by subcutaneous administration. The 2AMD analog was compared with
      another analog, 2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD),
      given at 5 ng/kg. RESULTS: After 28 days of cyclosporine administration with 5
      ng/kg 2AMD or 2MD, blood urea nitrogen levels were decreased by 20% and 30%, with
      no increase in serum calcium. This dose significantly decreased collagen levels
      by 50%, as determined by relative measurements of birefringence elicited under
      polarized light following picrosirius red staining of kidney tissues. The 20
      ng/kg dose of 2AMD was hypercalcemic, with consequent deleterious effects on
      measured parameters; however, all doses of 2AMD tested decreased collagen as
      determined by picrosirius staining. In Western blot analysis of extracts from rat
      kidneys treated with cyclosporine and 5 ng/kg 2AMD, the fibrotic markers,
      fibronectin and vimentin, were decreased compared with animals treated only with
      cyclosporine. CONCLUSIONS: We found that both vitamin D analogs are potent
      inhibitors of kidney fibrosis with potential renoprotective activity.

PMID- 29219792
TI  - [Unilateral blindness following a non-surgical rhinoplasty with filler].
AB  - BACKGROUND: A rare but known adverse event following a cosmetic filler treatment
      is unilateral blindness. In the Netherlands, this complication has not been
      reported in a patient before. CASE DESCRIPTION: A 26-year-old woman developed
      unilateral blindness after undergoing a cosmetic treatment of the dorsum nasi in
      which hyaluronic acid was used as filler. The blindness was caused by backflow of
      the filler via the ophthalmic artery into the carotid internal artery.
      CONCLUSION: There is no proven effective treatment for this adverse event.
      Therefore prevention is of great importance. This requires knowledge of the
      anatomy of the facial blood vessels and a well-developed injection technique.

PMID- 29219793
TI  - [Hypersensitivity reactions and vaccines].
AB  - - A lot of questions are being asked in the Netherlands about the safety of
      vaccination. More knowledge among care providers helps with regard to good
      medical practice and information.- Severe hypersensitivity reactions to vaccines
      are rare. Chicken-egg protein, gelatine and thiomersal are the most important
      vaccine components that may provoke severe reactions.- Acute treatment of
      patients with severe hypersensitivity reactions consists of intramuscular
      adrenaline.- In case of a severe reaction to a vaccine or a vaccine component,
      the subsequent course of action is determined by the physician referred to: the
      allergist or paediatric allergist. For most patients, vaccination or
      revaccination is possible in a setting where acute treatment is possible.- Slight
      side effects and delayed hypersensitivity reactions are not good reasons for
      additional measures with respect to vaccination.- It is important to record
      hypersensitivity reactions completely and unambiguously in the patient file.

PMID- 29219794
TI  - [A brown-red papule].
AB  - A 44-year-old woman was referred with a brown-red papule on the back.
      Histopathologic examination showed a melanocytic BAP1-associated intradermal
      tumour. A germline mutation in the BAP1 gene confirmed a diagnosis of BAP1 tumour
      predisposition syndrome. This syndrome is associated with various tumour types.
      Early diagnosis is essential for counselling and screening.

PMID- 29219795
TI  - [Platelet function tests: tailored antiplatelet therapy for vascular patients?]
AB  - - Platelet aggregation inhibitors, also known as antiplatelet therapy (APT), are
      prescribed for the prevention of secondary cardiovascular events (CVE) after
      endovascular revascularization procedures.- Platelet aggregation inhibitors are
      not equally effective in all patients. The phenomenon of high residual platelet
      reactivity despite APT is called 'high on-treatment platelet reactivity' (HTPR);
      it bears an increased risk of secondary CVE.- Platelet function tests (PFT) can
      be used to diagnose HTPR. There are various tests available; of those, light
      transmission aggregometry (LTA) is considered the gold standard. Some tests are
      only suitable for determining the effect of a certain category of APT.- Research
      into the usefulness of PFTs to optimise treatment with APT has not yet produced
      an unambiguous conclusion.- Currently there is not yet an indication for routine
      use of PFT in clinical practice. However, for the treatment of certain categories
      of patients with thromboembolic disease - such as those with renal failure or a
      history of kidney transplant - PFT can be considered.

PMID- 29219796
TI  - [An infant with moaning breathing].
AB  - A girl of 3.5 months old was presented at the emergency department because of
      sudden onset of moaning breathing. Clinical examination and imaging showed a
      congenital diaphragmatic hernia.

PMID- 29219797
TI  - [Timing of the care internship in the medical curriculum; when should students
      make acquaintance with older patients?]
AB  - A care internship in the first year of medical school is an effective way to help
      students learn to reflect and to acquire professional behaviour. Research has
      shown, however, that the impressions young medical students have of older people
      were not very positive before the care internship, and actually worsen
      afterwards. The care internship has now been adapted as result of these findings
      and on the basis of evidence in existing literature. Scientific evaluation of
      educational programmes, and studying potential side effects, are necessary to
      keep the medical curriculum effective and appropriate.

PMID- 29219798
TI  - [Guideline 'Organ donation following euthanasia"].
AB  - - The multidisciplinary guideline 'Organ donation following euthanasia' was
      published in March 2017 at request of the Minister of Health, Welfare and Sport.-
      This guideline provides recommendations for the organisation and implementation
      of a request to donate organs expressed by a patient who asks for euthanasia.- It
      is vital to avoid any conflict of interest while the patient requesting organ
      donation following euthanasia is still alive.- The person who carries out the
      euthanasia procedure is responsible for assessing the degree of unbearable
      suffering and for guaranteeing that potential organ donation is well-considered
      and voluntary.- During the procedure everything possible must be done to ensure a
      minimal burden for the patient and the family.

PMID- 29219799
TI  - [Characteristics and healthcare utilization of patients with highest costs of
      care].
AB  - OBJECTIVE: To determine characteristics and healthcare utilization of high-cost
      patients in the Netherlands. DESIGN: Cross-sectional study, using claim data for
      2013 from one Dutch health insurer. Analyses were limited to the curative health
      system (care that falls under the Health Insurance Act), including voluntary
      supplementary insurance. METHOD: We established total healthcare costs per
      beneficiary by summing all claims with a starting date in 2013. We categorized
      hospital-related diagnosis related groups (DRGs) and mental health care DRGs
      according to the ICD-10 International Classification of Diseases main chapters
      and sub-chapters. Per patient we determined which ICD-10-(sub-)chapter carried
      the highest costs. In addition, we developed several indicators for healthcare
      utilization and analysed healthcare utilization using descriptive statistics.
      Finally, we broke down high-cost patients by age group and compared
      characteristics and health care utilization between age groups. RESULTS: High
      cost patients, those in the top 1% in 2013, incurred an average total cost of
      over ? 56,000 per patient. They were treated by multiple providers for numerous
      health problems. Approximately one third of high-cost patients had one or more
      expensive treatments, including transplant surgery, dialysis, expensive drugs,
      intensive care unit use, or DRGs exceeding ? 30,000. The majority of high-cost
      patients were treated for cardiovascular disorders, neoplasms or mental and
      behavioural disorders. Though the high-cost patients were relatively old, more
      than half were younger than 65 years and average costs per patient decreased
      sharply with age. CONCLUSIONS: There is a need for an integral approach in the
      treatment of high-cost patients. Tailored policy and interventions are needed to
      improve care quality and to avoid unnecessarily high costs of care.

PMID- 29219800
TI  - [Social awareness campaign for a ban on consumer fireworks: 10 tips; doctor on
      the barricade].
AB  - - Describe the problem, and show why a social awareness campaign is needed- Know
      what you are talking about, and explain the medical jargon in plain language-
      Collect data and facts- Create support among colleagues- Get the media involved-
      Get support from the community- Create a coalition of supporters via a website-
      You will discover who the opposition is when you are on the barricade- Offer a
      safe and healthy alternative - Draw up a long-term roadmap, and persevere.

PMID- 29219801
TI  - [A focus on patients with the highest healthcare costs].
AB  - Wammes et al. (2017) showed that many of the patients who are among the 1% with
      the highest healthcare costs are being treated for multiple conditions. This
      suggests that high healthcare costs are at least partly due to treatment for
      multiple conditions, each of which by itself may not be excessively costly. It is
      the accumulation of costs for multiple conditions that cause patients to become
      high-cost patients, and this has implications for cost-control policies. It may
      be more worthwhile to focus on improving efficiency in the treatment of
      conditions that occur frequently but have low or medium costs than on conditions
      with high costs but that occur infrequently.

PMID- 29219802
TI  - In Situ High-Resolution Transmission Electron Microscopy (TEM) Observation of Sn
      Nanoparticles on SnO2 Nanotubes Under Lithiation.
AB  - We trace Sn nanoparticles (NPs) produced from SnO2 nanotubes (NTs) during
      lithiation initialized by high energy e-beam irradiation. The growth dynamics of
      Sn NPs is visualized in liquid electrolytes by graphene liquid cell transmission
      electron microscopy. The observation reveals that Sn NPs grow on the surface of
      SnO2 NTs via coalescence and the final shape of agglomerated NPs is governed by
      surface energy of the Sn NPs and the interfacial energy between Sn NPs and SnO2
      NTs. Our result will likely benefit more rational material design of the ideal
      interface for facile ion insertion.

PMID- 29219803
TI  - Accuracy and reproducibility of the Etest to detect drug-resistant Neisseria
      gonorrhoeae to contemporary treatment.
AB  - PURPOSE: Neisseria gonorrhoeae is a sexually transmitted bacterial pathogen that
      continues to evolve to become resistant to known antibiotics. In preparing for
      potential emergence, the Centers for Disease Control and Prevention recommends
      that clinical laboratories maintain or develop protocols to assess antibiotic
      susceptibly for this organism. This study examines the intra-laboratory
      variability of using the Etest method to provide consistent MIC values for N.
      gonorrhoeae and also compared the results of the Etest to known agar dilution MIC
      values. METHODOLOGY: Clinical N. gonorrhoeae isolates, 100 paired duplicates,
      were tested by eight laboratories for antibiotic susceptibility to ceftriaxone,
      cefixime and azithromycin using Etest strips.Results/Key findings. Overall, >80 %
      of the paired Etest MIC values were within one log2 dilution of the replicate.
      When compared to the agar dilution reference method, the cefixime Etest MIC
      values were consistently underreported by one dilution (seven laboratories) or
      two dilutions (one laboratory). The azithromycin Etest MIC values agreed 90.7 %
      with the agar dilution MIC values while the agreement with ceftriaxone was 90.9
      %. CONCLUSION: Overall, the Etest method yielded reproducible MIC values within
      each laboratory with the azithromycin and ceftriaxone MIC results consistent to
      the reference agar dilution method while the cefixime result tended to provide a
      lower MIC value.

PMID- 29219804
TI  - Pseudooceanicola lipolyticus sp. nov., a marine alphaproteobacterium,
      reclassification of Oceanicola flagellatus as Pseudooceanicola flagellatus comb.
      nov. and emended description of the genus Pseudooceanicola.
AB  - A Gram-stain-negative, rod-shaped bacterium, designated 157T, was isolated from
      seawater collected from the Philippine Sea. Cells of strain 157T grew in medium
      containing 0.5-10.0 % NaCl (w/v, optimum 3 %), at pH 6.0-8.5 (optimum 7.0) and at
      15-40  degrees C (optimum 30  degrees C). Tweens 20, 40 and 80 as well as urea
      were hydrolysed. The 16S rRNA gene sequence of strain 157T had a high sequence
      similarity with respect to Pseudooceanicola marinus AZO-CT (97.2 %), and
      exhibited less than 97.0 % sequence similarity to other type strains of the
      species with validly published names. Phylogenetic analyses revealed that strain
      157T fell within a cluster comprising the Pseudooceanicola species and formed a
      coherent clade with P. marinus AZO-CT and Pseudooceanicola antarcticus Ar-45T.
      Strain 157T exhibited average nucleotide identity values of 74.5 and 74.9 % to P.
      marinus LMG 23705T and P. antarcticus Ar-45T, respectively. In silico DNA-DNA
      hybridization analysis revealed that strain 157T shared 20.2 % DNA relatedness
      with P. marinus LMG 23705T and 20.6 % with P. antarcticus Ar-45T, respectively.
      The sole isoprenoid quinone was ubiquinone 10. The major fatty acids were summed
      feature 8 (C18 : 1omega7c and/or C18 : 1omega6c), C19 : 0 cyclo omega8c, C16 : 0
      2-OH and C16 : 0. The major polar lipids were phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and
      one unidentified glycolipid. The DNA G+C content was 64.6 mol%. According to the
      phylogenetic, chemotaxonomic and phenotypic data, it represents a novel species
      of the genus Pseudooceanicola, for which the name Pseudooceanicolalipolyticus is
      proposed. The type strain is 157T (=KCTC 52654T=MCCC 1K03317T). In addition, the
      description of the genus Pseudooceanicola is emended and Oceanicola flagellatus
      is reclassified as Pseudooceanicola flagellatus comb. nov., with the type strain
      DY470T (=CGMCC 1.12664T=LMG 27871T) proposed.

PMID- 29219805
TI  - CAR gene cluster and transcript levels of carotenogenic genes in Rhodotorula
      mucilaginosa.
AB  - A molecular approach was applied to the study of the carotenoid biosynthetic
      pathway of Rhodotorula mucilaginosa. At first, functional annotation of the
      genome of R. mucilaginosa C2.5t1 was carried out and gene ontology categories
      were assigned to 4033 predicted proteins. Then, a set of genes involved in
      different steps of carotenogenesis was identified and those coding for phytoene
      desaturase, phytoene synthase/lycopene cyclase and carotenoid dioxygenase (CAR
      genes) proved to be clustered within a region of ~10 kb. Quantitative PCR of the
      genes involved in carotenoid biosynthesis showed that genes coding for 3-hydroxy
      3-methylglutharyl-CoA reductase and mevalonate kinase are induced during
      exponential phase while no clear trend of induction was observed for phytoene
      synthase/lycopene cyclase and phytoene dehydrogenase encoding genes. Thus, in R.
      mucilaginosa the induction of genes involved in the early steps of carotenoid
      biosynthesis is transient and accompanies the onset of carotenoid production,
      while that of CAR genes does not correlate with the amount of carotenoids
      produced. The transcript levels of genes coding for carotenoid dioxygenase,
      superoxide dismutase and catalase A increased during the accumulation of
      carotenoids, thus suggesting the activation of a mechanism aimed at the
      protection of cell structures from oxidative stress during carotenoid
      biosynthesis. The data presented herein, besides being suitable for the
      elucidation of the mechanisms that underlie carotenoid biosynthesis, will
      contribute to boosting the biotechnological potential of this yeast by improving
      the outcome of further research efforts aimed at also exploring other features of
      interest.

PMID- 29219806
TI  - Mucilaginibacter amnicola sp. nov., isolated from a freshwater creek.
AB  - A pink-coloured bacterial strain, TAPP7T, was isolated from a freshwater creek in
      Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain
      TAPP7T belonged to the genus Mucilaginibacter and showed highest similarity with
      Mucilaginibacter ginsengisoli B4Y-8T (97.6 %) and Mucilaginibacter carri PR0008KT
      (96.9 %). Cells of strain TAPP7T were Gram-staining-negative, aerobic, poly-beta
      hydroxybutyrate-accumulating and short-rod-shaped. Growth occurred at 10-30 
      degrees C (optimum, 15-20  degrees C), at pH 4-8 (optimum, pH 6) and with 0-1 %
      NaCl (optimum, 0.5 %). The predominant fatty acids were summed feature 3 (C16 :
      1omega7c and/or C16 : 1omega6c) and iso-C15 : 0. The polar lipid profile
      consisted of phosphatidylethanolamine and several uncharacterized
      aminophospholipids and phospholipids. The major polyamine was homospermidine. The
      major isoprenoid quinone was MK-7. The DNA G+C content of the genomic DNA was
      45.6 mol%. The DNA-DNA relatedness of strain TAPP7T with respect to
      Mucilaginibacter ginsengisoli B4Y-8T was less than 35 %. On the basis of the
      phylogenetic inference and phenotypic data, strain TAPP7T should be classified as
      a novel species, for which the name Mucilaginibacter amnicola sp. nov. is
      proposed. The type strain is TAPP7T (=BCRC 80976T=LMG 29556T=KCTC 52238T).

PMID- 29219807
TI  - Down-regulation of cellular protein heme oxygenase-1 inhibits proliferation of
      avian influenza virus H9N2 in chicken oviduct epithelial cells.
AB  - The pathogenesis of H9N2 subtype avian influenza virus (AIV) infection in hens is
      often related to oviduct tissue damage. Our previous study suggested that H9N2
      AIV induces cellular apoptosis by activating reactive oxygen species (ROS)
      accumulation and mitochondria-mediated apoptotic signalling in chicken oviduct
      epithelial cells (COECs). Heme oxygenase-1 (HO-1) is an inducible enzyme that
      exerts protective effects against oxidative stress and activated HO-1 was
      recently shown to have antiviral activity. To study the potential involvement of
      HO-1 in H9N2 AIV proliferation, the role of its expression in H9N2-infected COECs
      was further investigated. Our results revealed that H9N2 AIV infection
      significantly up-regulated the expression of HO-1 and that HO-1 down-regulation
      by ZnPP, a classical inhibitor of HO-1, could inhibit H9N2 AIV replication in
      COECs. Similarly, the small interfering RNA (siRNA)-mediated knockdown of HO-1
      also markedly decreased the virus production in H9N2-infected COECs. In contrast,
      adenoviral-mediated over-expression of HO-1 concomitantly promoted H9N2 AIV
      replication. Taken together, our study demonstrated the involvement of HO-1 in
      AIV H9N2 proliferation, and these findings suggested that HO-1 is a potential
      target for inhibition of AIV H9N2 replication.

PMID- 29219808
TI  - Ferrovibrio soli sp. nov., a novel cellulolytic bacterium isolated from stream
      bank soil.
AB  - Two isolates of bacterial strains A15T and A17 were isolated from stream bank
      soil in Kyonggi University. Cells were aerobic, Gram-stain-negative, oxidase- and
      catalase-positive, motile, non-spore-forming, rod-shaped, opaque, and cream
      coloured. Both strains hydrolysed CM-cellulose. Strains were able to grow at 20
      42  degrees C, pH 5.5-10.0 and at 1.5 % NaCl concentration (w/v). Indole test was
      positive. Analyses of phylogenetic trees based on its 16S rRNA gene sequences
      indicated that strain A15T formed a lineage within the family Rhodospirillaceae
      of the phylum Proteobacteria which was distinct from Ferrovibrio denitrificans
      S3T (98.4 % sequence similarity) and Ferrovibrio xuzhouensis LM-6T (97.4 %). The
      sole detected respiratory quinone was Q-10. The major polar lipids were
      phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminolipid.
      The major cellular fatty acids were C19 : 0 cycloomega8c, C16 : 0, summed feature
      8 (C18 : 1omega7c and/or C18 : 1omega6c), C18 : 0cyclo and C12 : 0. The DNA G+C
      contents of strains A15T and A17 were 63.4 and 62.9 mol%, respectively. DNA-DNA
      relatedness between strain A15T and other two members of the genus
      Ferrovibrioranged from 25 to 37 %. The polyphasic characterization revealed
      strains A15T and A17 represent a novel species in the genus Ferrovibrio, for
      which the name Ferrovibriosoli sp. nov. is proposed. The type strain is A15T
      (=KEMB 9005-522T=KACC 19102T=NBRC 112682T).

PMID- 29219809
TI  - The cell wall of the filamentous anoxygenic phototrophic bacterium Oscillochloris
      trichoides.
AB  - The filamentous anoxygenic phototrophic bacterium Oscillochloris trichoides DG-6
      has been studied, and it has been shown that there are no lipopolysaccharides on
      the cell surface. Fatty acids hydroxylated at the C3 position, amino sugars and
      phosphate-containing compounds characteristic of lipid A have also not been
      found. The genes encoding for proteins responsible for the synthesis of
      lipopolysaccharides and the genes for the transport system, usually localized in
      the outer membrane of Gram-negative bacteria, have not been detected in the
      genome. The rigid layer of the cell wall contains a peptidoglycan consisting of
      alanine, glutamine, ornithine and glycine, in the respective ratio 1.8 : 1.5 :
      1.0 : 0.6. Thus, the investigated bacterium, Osc. trichoides, is a monoderm. The
      cell wall also contains a branched alpha-1,4-d-glucan with a repeating unit
      consisting of glucose residues linked by alpha-1->4 bonds (alpha-1->6 at the
      branching sites). Such polymers have not previously been reported in phototrophic
      bacteria.

PMID- 29219810
TI  - Optimising the ISAR-HP to screen efficiently for functional decline in older
      patients.
AB  - INTRODUCTION: The Identification of Seniors At Risk-Hospitalised Patients (ISAR
      HP) has recently been included in guidelines as a frailty indicator to identify
      patients for comprehensive geriatric assessment. Previous studies showed that the
      conventional cut-off score incorrectly classifies a high percentage of patients
      as high risk. We aimed to optimise the predictive value of ISAR-HP by using
      different cut-offs in older acutely hospitalised patients. METHODS: A prospective
      follow-up study was performed in two Dutch hospitals. Acutely hospitalised
      patients aged >= 70 years were included. Demographics, illness severity
      parameters, geriatric measurements and the ISAR-HP scores were obtained at
      baseline. The primary outcome was a combined end point of functional decline or
      mortality during 90-day follow-up. RESULTS: In total 765 acutely hospitalised
      older patients were included, with a median age of 79 years, of whom 276 (36.1%)
      experienced functional decline or mortality. The conventional ISAR-HP cut-off of
      >= 2 assigned 432/765 patients (56.5%) as high risk, with a positive predictive
      value (PPV) of 0.49 (95%CI 0.45-0.54) and a negative predictive value of 0.81
      (95%CI 0.76-0.85). Thus, 51% of those whom the ISAR-HP denoted as high risk did
      not experience the outcome of interest. Raising the cut-off to >= 4 assigned
      205/765 patients (26.8%) as high risk, with a marginally increased PPV to 0.55
      (95%CI 0.48-0.62). CONCLUSION: The ISAR-HP with the conventional cut-off of >= 2
      incorrectly identifies a large group of patients at high risk for functional
      decline or mortality and raising the cut-off to 4 only marginally improved
      performance. Caution is warranted to ensure efficient screening and follow-up
      interventions.

PMID- 29219811
TI  - Non-targeted HIV screening in emergency departments in the Netherlands.
AB  - BACKGROUND: In the Netherlands a substantial proportion of newly diagnosed human
      immunodeficiency virus (HIV) patients present late for care and an estimated 12
      34% of people living with HIV are undiagnosed. Linkage to care of these patients
      is important to decrease HIV transmission and to improve individual patient
      outcomes. We investigated if non-targeted HIV testing in emergency departments is
      a useful and cost-effective way to identify these patients. METHODS: In a cross
      sectional multicentre study, eligible adult patients who underwent phlebotomy
      were given an active choice to be additionally tested for HIV. In a subset of
      patients, risk factors for HIV infection were asked for. A cost-effectiveness
      analysis was conducted. RESULTS: Of 7577 eligible patients, 3223 patients were
      tested, and two new HIV infections were diagnosed (0.06%). Both patients had risk
      factors for HIV infection. Non-targeted HIV testing in the emergency department
      was not considered cost-effective, with a cost per quality adjusted life years
      gained of ? 77,050, more than triple the Dutch cost-effectiveness threshold of ?
      20,000. CONCLUSION: Non-targeted HIV testing in emergency departments in the
      Netherlands had a low yield of newly diagnosed HIV infections and was not cost
      effective. Our data suggest that targeted HIV testing may offer an alternative
      approach to decrease the number of undiagnosed people living with HIV.

PMID- 29219812
TI  - Helicobacter pylori resistance in the Netherlands: a growing problem?
AB  - Helicobacter pylori infection is clinically associated with dyspepsia, gastric
      and duodenal ulcers, and gastric cancer. Increasing antimicrobial resistance in
      H. pylori is a worldwide problem and failure of eradication with standard triple
      therapy (high-dose proton pump inhibition, amoxicillin and clarithromycin) is
      directly related to the presence of a resistant strain. Other treatment
      combinations have been investigated, but with inconsistent results. Based on a
      review of the recent literature in conjunction with an analysis of the regional
      resistance data, we address the increasing complexity of H. pylori eradication
      therapy. Culture and susceptibility results of all first H. pylori isolates of
      adults (> 18 years) seen in the Leiden University Medical Center, from January
      2006 to December 2015, were analysed (n = 707). An increase in clarithromycin
      resistance was observed from 9.8% to 18.1% (p = 0.002) in the periods from 2006
      2010 and 2011-2015, respectively. For ampicillin the resistance increased from
      6.3% to 10.0% (p = 0.37), and for metronidazole from 20.7% to 23.2% (p = 0.42).
      The tetracycline resistance remained low at 3.2% and 2.3%, respectively. The
      treatment paradigm is shifting towards individualised treatment rather than a one
      strategy-fits-all approach. In case of treatment failure it should be strongly
      considered to refer a patient for endoscopy, biopsy and culture. Thereafter,
      targeted antimicrobial treatment based on susceptibility results can be
      initiated. Furthermore, accumulating data indicate that prolongation of treatment
      to 14 days, as opposed to the current standard 7 day course, contributes to a
      higher H. pylori eradication rate.

PMID- 29219813
TI  - Unfavourable blood pressure and LDL-cholesterol levels in obese non-diabetic
      individuals.
AB  - BACKGROUND: Early diagnosis and treatment of high blood pressure (BP) and
      cholesterol is important to reduce cardiovascular risk. We compared BP and LDL
      cholesterol (LDL-C) as well as the quality of treatment between obese subjects
      and normal weight and overweight individuals. METHODS: 87,648 participants of the
      Lifelines study were categorised according to obesity (normal weight/
      overweight/obesity) and age. Mean systolic BP and LDL-C were calculated depending
      on treatment, BMI, age and sex. RESULTS: In all age groups, except those aged 70
      80 years, women had a significantly lower BP than men. Use of BP-lowering
      medication did not result in BP levels comparable with non-users, except in those
      aged 70-80 years. Despite medication, the BP was insufficiently controlled in 20
      50% of participants. BP was significantly higher in obese vs. normal weight and
      overweight individuals of all ages, but most apparently in men younger than 50
      years. Mean LDL-C varied between 2.5- .0 mmol/l. Despite higher statin use, obese
      participants had a higher LDL-C than those with a normal weight. Statins
      abolished the age-dependent LDL-C increase. Many participants did not achieve
      target LDL-C < 2.5 mmol/l. A small percentage of individuals treated with BP
      lowering drugs were also using statins (overall 32% in men, 17% in women).
      CONCLUSION: Obese individuals, especially men younger than 50, have a higher BP
      and LDL-C compared with those with overweight and a normal weight. Use of BP
      lowering drugs did not revert the BP back to levels normal for the specific age
      and BMI group, whereas statins abolished the age-related increase in LDL-C. These
      data suggest that more attention is needed for active screening and treatment of
      cardiovascular risk factors.

PMID- 29219814
TI  - Cellulitis: current insights into pathophysiology and clinical management.
AB  - Cellulitis is a bacterial skin and soft tissue infection which occurs when the
      physical skin barrier, the immune system and/or the circulatory system are
      impaired. Diabetes, obesity and old age are associated with defects in all of
      these areas and as a result are major predisposing factors for cellulitis. In
      this review, we summarise current insights into the pathophysiology of cellulitis
      and place the Dutch guidelines on the clinical management of cellulitis of the
      lower extremities in perspective. Recent evidence on diagnostic strategies is
      discussed, the importance of which is underscored by findings that venous
      insufficiency, eczema, deep vein thrombosis and gout are frequently mistaken for
      cellulitis. Empiric antibiotic choices are designed against the background of a
      low prevalence of multi-resistant Staphylococcus aureus. Novel antimicrobial
      agents registered for cellulitis are also discussed. Relapses occur frequently
      due to a high prevalence of risk factors associated with cellulitis in
      combination with the ccurrence of persistent post-inflammatory lymphatic damage.
      Lastly, we identify knowledge gaps which, if addressed, will advance our
      understanding of the pathophysiology of cellulitis and improve its clinical
      management.

PMID- 29219815
TI  - Hitting the right target: Diagnosing undiagnosed HIV patients in the Netherlands.

PMID- 29219816
TI  - Nephrotic syndrome due to lupus-like glomerulonephritis in an HIV-positive
      patient.
AB  - Lupus nephritis, a well-known complication in systemic lupus erythematosus, is
      characterised by a proliferative glomerulonephritis or membranous nephropathy
      along with a full-house immunofluorescence pattern on renal biopsy. There are
      very few exceptions in which similar histopathological findings are present, but
      case reports show that an increasing number of HIV-positive patients (mostly
      black Africans, but also white patients) have HIV-immune complex disease
      (HIVICK), which can mimic lupus nephritis. Lupus-like HIVICK is treated
      differently than 'true' lupus nephritis, so distinction is warranted.

PMID- 29219817
TI  - Donor-derived tuberculosis via orthotopic liver transplantation.
AB  - We present a case of donor-derived tuberculosis after liver transplantation, in
      which the donor origin of the Mycobacterium tuberculosis isolate was made most
      likely by DNA fingerprinting. Screening for latent tuberculosis of transplant
      donors originating from high endemic areas with an ex-vivo interferon-gamma
      release assay should be considered.

PMID- 29219819
TI  - Answer to Photo Quiz: Granulating wound after a holiday in Peru.

PMID- 29219818
TI  - Granulating wound after a holiday in Peru.

PMID- 29219821
TI  - Answer to Photo Quiz: A rare cause of abdominal mass and deep venous thrombosis.

PMID- 29219820
TI  - A rare cause of abdominal mass and deep venous thrombosis.

PMID- 29219822
TI  - A blood smear on admission.

PMID- 29219823
TI  - Answer to Photo Quiz: A blood smear on admission.

PMID- 29219824
TI  - Thyrotoxic periodic paralysis: an unusual presentation of hyperthyroidism.
AB  - Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism among
      Asians, characterised by sudden onset of hypokalaemia and muscle paralysis.
      Several factors may contribute to a delay in diagnosis, including the subtlety of
      hyperthyroidism, the transient nature of the events and the rarity of this
      disease in the West. As life-threatening arrhythmias may occur during an attack,
      awareness among physicians is necessary for early recognition and treatment.
      Advances have been made in understanding the pathophysiological mechanism leading
      to hypokalaemia, which include recently identified mutations of the inwardly
      rectifying potassium channel Kir2.6. Treatment includes the supplementation of
      potassium, a nonselective beta-blocker, and ultimately treatment of the
      underlying hyperthyroidism. Here we report three cases of TPP in the Netherlands,
      and review the literature on clinical features, pathophysiological hypothesis and
      treatment.

PMID- 29219825
TI  - Ending the epidemic: Critical role of primary HIV infection.
AB  - Early identification and immediate treatment of individuals newly infected with
      HIV is important for two reasons: it benefits the long-term health of the
      infected patient, and it reduces onward HIV transmission. Primary HIV infection
      (PHI) reflects the period following HIV acquisition during which viraemia bursts
      until the establishment of a stable plasma HIV-RNA level approximately six months
      post infection. During this period, patients are particularly contagious and are
      often unaware of the infection. As a consequence, PHI disproportionally affects
      onward transmission. During PHI the immune system is irreparably damaged and
      persistent viral reservoirs are formed. Initiating antiretroviral therapy (ART)
      during PHI could potentially lead to a functional cure through early and
      prolonged viral suppression. Unfortunately, symptoms of PHI are nonspecific and
      the diagnosis is frequently missed. This impedes timely diagnosis and prompt
      initiation of ART. To increase awareness and underscore the importance of
      immediate ART initiation, we describe here the pathogenesis, clinical
      presentation, and impact of treating PHI.

PMID- 29219826
TI  - Is there a need for dietary consultation in elderly non-European migrants?

PMID- 29219827
TI  - Venous thrombosis and coagulation parameters in patients with pure venous
      malformations.
AB  - INTRODUCTION: Venous malformations (VMs) are ubiquitous, low-flow vascular
      anomalies known to be occasionally painful due to thrombotic episodes within the
      lesion. The prevalence of superficial or deep vein thrombosis is unclear.
      METHODS: A cross-sectional study among outpatients aged >= 12 years with pure VMs
      was performed, quantifying the prevalence of thrombosis by screening all patients
      with compression ultrasonography (CUS). Additionally, we evaluated whether
      coagulation alterations were related to thrombosis observed with CUS. RESULTS: In
      total, 69 patients with pure VMs were eligible, median age was 30 years (range 12
      63) and 52% were female. A total of 68 patients underwent CUS. Superficial vein
      thrombosis was observed in 10 (15%) cases; 1 patient had a current asymptomatic
      deep venous thrombosis. Residual superficial or deep thrombosis was observed in
      25 patients (36%). In total, 49% had either a history or current signs of a
      thrombotic event and overall 10% had venous thromboembolism. In approximately 50%
      of the patients the D-dimer level was above 0.5 mg/l. Median P-selectin and Von
      Willebrand factor levels were 29 ng/ml (interquartile range (IQR) 21-34) and 108%
      (IQR 83-132), respectively. No differences were observed in the coagulation
      parameters between the patients with and without current clots in their VM.
      CONCLUSION: This study shows that superficial or deep vein thrombosis is common
      among patients with a pure VM. Physicians should be aware of this high incidence,
      especially if other risk factors for thrombosis are present.

PMID- 29219828
TI  - Improving care for older patients in the acute setting: a qualitative study with
      healthcare providers.
AB  - BACKGROUND: The proportion of older people needing acute care is rapidly growing,
      thereby posing an increased burden on the acute care chain. The aim of this study
      is to gain more insight into the obstacles and potential improvement
      opportunities of the acute care process for older patients arriving at the
      hospital. METHODS: Semi-structured interviews were conducted to determine the
      experiences of 18 different primary (i.e. general practitioner, community nurse)
      and secondary healthcare professionals (i.e. emergency department (ED) nurse, ED
      physician, geriatric physician, geriatric nurse, ambulance nurse, acute medical
      unit nurse), and three experts (2 researchers, 1 older adult advisor). RESULTS:
      Four core themes emerged from the interviews: 1) The concept of frailty,
      awareness concerning frail older patients, and identification of frailty, 2)
      Barriers in the care process of older patients within the acute care chain, 3)
      Optimising the discharge process of older patients, and 4) Improvement
      opportunities suggested by the respondents. Early identification of frailty,
      improving the continuity of care by means of structured information exchange
      between care providers in the acute care chain, and a more generalist approach
      were considered important by the respondents in order to deliver appropriate care
      to older patients. CONCLUSION: This explorative study identified several barriers
      and improvement opportunities which are important to improve the quality,
      efficacy and appropriateness of the acute care of older patients. More seems
      needed in the future in order to share experiences, expertise and develop
      potential improvement strategies for the acute care of older patients.

PMID- 29219829
TI  - Prevalence of iron deficiency in a Dutch geriatric migrant population.
AB  - BACKGROUND: The prevalence of iron deficiency anaemia (IDA) rises with age.
      Migrants are potentially at higher risk for IDA because of differences in intake
      and uptake as well as their higher comorbid status. We assessed whether geriatric
      Turkish and Moroccan migrants have a higher prevalence of low iron status and
      IDA. METHODS: Retrospective case-control study in a geriatric outpatient clinic
      (2012-2015). In total, 188 consecutive Turkish and Moroccan migrants aged >= 65
      years were included and matched with 188 Dutch controls. Matching was based on
      the visiting date of the patients. Main outcome measures were serum ferritin
      level (below 15 ug/l) and IDA. IDA was defined as anaemia according to the WHO
      definition, with a serum ferritin level below 15 ug/l and serum CRP below 10
      mg/l. Multivariate logistic regression was performed to correct for confounders.
      RESULTS: Mean serum ferritin level was significantly lower in migrants (83.46
      ug/l, SD 106.8 vs. 164.94 ug/l, SD 160.1, (p < 0.05)). In total, 7.4% met the IDA
      criteria, of these 5.6% were migrants and 1.8% were Dutch (p < 0.05). After
      correction for age, gender, BMI, and use of NSAIDs, a low ferritin level was
      associated with migrant status (OR 3.0, 95% CI 1.0-8.9) as was IDA (OR 2.9, 95%
      CI 1.2-7.2). CONCLUSION: Prevalence of low serum ferritin and IDA is increased in
      the first-generation Turkish and Moroccan geriatric migrant population. This
      might be caused by differences in iron intake or uptake from nutrition between
      the populations or because of gastrointestinal pathology; further study is
      warranted.

PMID- 29219830
TI  - A rare case of Waterhouse- Friderichsen syndrome during primary Varicella zoster
      infection.
AB  - Primary Varicella zoster virus infection in adults is associated with a higher
      risk of complications when compared with the benign disease course of primary
      infection during childhood. We present a rare complication of adult primary
      Varicella zoster in the form of acute, irreversible adrenal insufficiency due to
      bilateral adrenal haemorrhage, which is also known as the
      WaterhouseFriderichsensyndrome.

PMID- 29219831
TI  - Female urothelial cell carcinoma in a failed kidney graft of a male recipient.
AB  - We present a case of a male kidney transplant patient harbouring two kidney
      grafts of which one is functional. In the failed graft, he developed urothelial
      cell carcinoma with cells containing XX-chromosome, and female tumour cells were
      also found in the bladder. The patient underwent donor nephrectomy, was treated
      with epirubicin bladder instillations, and immunosuppression was tapered. Less
      than a year before re-transplantation a CT scan showed no abnormalities of the
      first graft. Transplantectomy before a second kidney transplantation is debated.

PMID- 29219832
TI  - Spontaneous rupture of a splenic artery aneurysm in a male patient.

PMID- 29219833
TI  - Answer to Photo Quiz: Spontaneous rupture of a splenic artery aneurysm in a male
      patient.

PMID- 29219834
TI  - A 52-year-old oncology patient with acute severe abdominal pain.

PMID- 29219835
TI  - Answer to Photo Quiz: A 52-year-old oncology patient with acute severe abdominal
      pain.

PMID- 29219837
TI  - Answer to Photo Quiz: What's the cause of this patient's angina?

PMID- 29219836
TI  - What's the cause of this patient's angina?

PMID- 29219838
TI  - Surface plasmon of three-dimensional Dirac semimetals.
AB  - The surface plasmon excitation spectrum is calculated for the semi-infinite 3D
      Dirac semimetal. We used the random phase approximation for the calculation of
      the surface dielectric function, from which we derived the dynamical structure
      factor. The surface excitation spectrum shows a well-defined strong surface
      plasmon peak due to the plasmon mode in the bulk, with a noticeable influence of
      electron-hole excitations at large wave vectors parallel to the surface. The
      obtained spectrum will be useful for experimentally exploring the surface
      spectral properties of 3D topological Dirac semimetals.

PMID- 29219839
TI  - Efficient exfoliation of layered materials by waste liquor.
AB  - Based on their unique material properties, two-dimensional (2D) nanomaterials
      such as graphene, molybdenum disulfide (MoS2), and boron nitride (BN) have been
      attracting increased research interest. The potential of 2D materials, in the
      form of nanoplatelets that are used as new materials, will be important to both
      nanomaterials and advanced materials. Water is usually considered to be the ideal
      dispersed medium, and the essential hydrophobicity and limitations to mass
      production of 2D nanoplatelets have become quite serious obstacles to their usage
      in various fields. In this paper, pulping black liquor was used as dispersant,
      with high concentration of lignin to get single- and few-layered nanoplatelets.
      The whole process required only the high-shear mixing of 2D layered materials and
      pulping waste liquor. This method was not only simple and efficient but also
      environmentally friendly and resource-recycling. Moreover, the fabricated single-
      or few-layered nanoplatelets possessed good solubility in aqueous solution due to
      their edge functionalization, and could be well dispersed in water at
      concentrations (10 mg ml-1 for graphene, 6.3 mg ml-1 for MoS2, and 6.0 mg ml-1
      for BN) which were much higher than that of other methods. The dispersions of
      graphene, MoS2, and BN nanosheets were highly stable over several months, which
      allowed us to easily prepare graphene, MoS2, and BN films through simple vacuum
      filtration or spraying. These results indicated that pulping black liquor can be
      used as a material or reagent, and the mass production of 2D material is possible
      in a simple and fast method.

PMID- 29219840
TI  - Visible-light-induced Ag/BiVO4 semiconductor with enhanced photocatalytic and
      antibacterial performance.
AB  - An Ag-loaded BiVO4 visible-light-driven photocatalyst was synthesized by the
      microwave hydrothermal method followed by photodeposition. The photocatalytic
      performance of the synthesized samples was evaluated on a mixed dye (methylene
      blue and rhodamine B), as well as bisphenol A in aqueous solution. Similarly, the
      disinfection activities of synthesized samples towards the Gram-negative
      Escherichia coli (E. coli) in a model cell were investigated under irradiation
      with visible light (lambda >= 420 nm). The synthesized samples have monoclinic
      scheelite structure. Photocatalytic results showed that all Ag-loaded BiVO4
      samples exhibited greater degradation and a higher mineralization rate than the
      pure BiVO4, probably due to the presence of surface plasmon absorption that
      arises due to the loading of Ag on the BiVO4 surface. The optimum Ag loading of 5
      wt% has the highest photocatalytic performance and greatest stability with pseudo
      first-order rate constants of 0.031 min-1 and 0.023 min-1 for the degradation of
      methylene blue and rhodamine B respectively in a mixture with an equal volume and
      concentration of each dye. The photocatalytic degradation of bisphenol A reaches
      76.2% with 5 wt% Ag-doped BiVO4 within 180 min irradiation time. Similarly, the
      Ag-loaded BiVO4 could completely inactivate E. coli cells within 30 min under
      visible light irradiation. The disruption of the cell membrane as well as
      degradation of protein and DNA exhibited constituted evidence for antibacterial
      activity towards E. coli. Moreover, the bactericidal mechanisms involved in the
      photocatalytic disinfection process were systematically investigated.

PMID- 29219841
TI  - Direct observation of thermal disorder and decomposition of black phosphorus.
AB  - Theoretical research has been devoted to reveal the properties of black
      phosphorus as a two-dimensional nanomaterial, but little attention has been paid
      for the experimental characterization. In this study, the thermal disorder and
      decomposition of black phosphorus were examined using in situ heating
      transmission electron microscopy experiments. We observed that the breaking of
      crystallographic symmetry begins at 380  degrees C under vacuum condition,
      followed by the phosphorus evaporates after long-term heating at 400  degrees C.
      This decomposition process can be initiated by the surficial vacancy and proceeds
      toward both interlayer ([010]) and intralayer ([001]) directions. The results on
      the thermal behavior of black phosphorus provide useful guidance for thin film
      deposition and fabrication processes with black phosphorus.

PMID- 29219842
TI  - Thermal expansion producing easier formation of a black phosphorus nanotube from
      nanoribbon on carbon nanotube.
AB  - As a novel one-dimensional material having excellent electrical properties, a
      black phosphorus (BP) nanotube has wide potential applications in nanodevices. A
      BP nanotube has not yet, however, been discovered in experiments or fabricated
      via chemical synthesis. In this study, the feasibility of forming a nanotube from
      a parallelogram nanoribbon upon a carbon nanotube (CNT) at different temperatures
      is discussed through the use of molecular dynamics simulations. Results obtained
      demonstrate that an ideal BP nanotube from the same nanoribbon can be obtained
      via self-assembly on a CNT at 50 K or lower temperature. At temperatures between
      50-100 K, the BP nanotube formed from a single ribbon has defects at both ends.
      When the temperature is higher than 100 K, it is difficult to obtain a BP
      nanotube of high quality. It is discovered that when the ribbon can only wind
      upon the same CNT at low temperature, it may form into an ideal nanotube by
      increasing the temperature of the system. The reason is that the BP ribbon has a
      higher thermal expansion than the CNT under the same temperature difference.

PMID- 29219843
TI  - Negative differential resistance effect induced by metal ion implantation in SiO2
      film for multilevel RRAM application.
AB  - Pt/SiO2:metal nanoparticles/Pt sandwich structure is fabricated with the method
      of metal ion (Ag) implantation. The device exhibits multilevel storage with
      appropriate R off/R on ratio, good endurance and retention properties. Based on
      transmission electron microscopy and energy dispersive spectrometer analysis, we
      confirm that Pt nanoparticles are spurted into SiO2 film from Pt bottom electrode
      by Ag implantation; during electroforming, the local electric field can be
      enhanced by these Pt nanoparticles, meanwhile the Ag nanoparticles constantly
      migrate toward the Pt nanoparticles. The implantation induced nanoparticles act
      as trap sites in the resistive switching layer and play critical roles in the
      multilevel storage, which is evidenced by the negative differential resistance
      effect in the current-voltage (I-V) measurements.

PMID- 29219844
TI  - Amine treatment induced perovskite nanowire network in perovskite solar cells:
      efficient surface passivation and carrier transport.
AB  - In the fabrication of high efficiency organic-inorganic metal halide perovskite
      solar cells (PSCs), an additional interface modifier is usually applied for
      enhancing the interface passivation and carrier transport. In this paper, we
      develop an innovative method with in-situ growth of one-dimensional perovskite
      nanowire (1D PNW) network triggered by Lewis amine over the perovskite films. To
      our knowledge, this is the first time to fabricate PSCs with shape-controlled
      perovskite surface morphology, which improved power conversion efficiency (PCE)
      from 14.32% to 16.66% with negligible hysteresis. The amine molecule can
      passivate the trap states on the polycrystalline perovskite surface to reduce
      trap-state density. Meanwhile, as a fast channel, the 1D PNWs would promote
      carrier transport from the bulk perovskite film to the electron transport layer.
      The PSCs with 1D PNW modification not only exhibit excellent photovoltaic
      performances, but also show good stability with only 4% PCE loss within 30 days
      in the ambient air without encapsulation. Our results strongly suggest that in
      situ grown 1D PNW network provides a feasible and effective strategy for
      nanostructured optoelectronic devices such as PSCs to achieve superior
      performances.

PMID- 29219845
TI  - Double-walled silicon nanotubes: an ab initio investigation.
AB  - The synthesis of silicon nanotubes realized in the last decade demonstrates multi
      walled tubular structures consisting of Si atoms in [Formula: see text] and the
      [Formula: see text] hybridizations. However, most of the theoretical models were
      elaborated taking as the starting point [Formula: see text] structures analogous
      to carbon nanotubes. These structures are unfavorable due to the natural tendency
      of the Si atoms to undergo [Formula: see text]. In this work, through ab initio
      simulations based on density functional theory, we investigated double-walled
      silicon nanotubes proposing layered tubes possessing most of the Si atoms in an
      [Formula: see text] hybridization, and with few [Formula: see text] atoms
      localized at the outer wall. The lowest-energy structures have metallic behavior.
      Furthermore, the possibility to tune the band structure with the application of a
      strain was demonstrated, inducing a metal-semiconductor transition. Thus, the
      behavior of silicon nanotubes differs significantly from carbon nanotubes, and
      the main source of the differences is the distortions in the lattice associated
      with the tendency of Si to make four chemical bonds.

PMID- 29219846
TI  - Organic-inorganic hybrid optical foils with strong visible reflection, excellent
      near infrared-shielding ability and high transparency.
AB  - Research on functional flexible films has recently been attracting widespread
      attention especially with regards to foils, which can be designed artificially on
      the basis of the practical requirements. In this work, a foil with high visible
      reflection and a strong near infrared shielding efficiency was prepared by a
      simple wet chemical method. In the process of making this kind of optical foil,
      emulsion polymerization was first introduced to synthesize polymer opals, which
      were further compressed between two pieces of polyethylene terephthalate (PET)
      foil under polymer melting temperature to obtain a photonic crystal film with a
      strong reflection in the visible region to block blue rays. The following step
      was to coat a layer of the inorganic nano paint, which was synthesized by
      dispersing Cs-doped WO3 (CWO) nanoparticles homogenously into organic resin on
      the surface of the PET to achieve a high near infrared shielding ability. The
      final composite foil exhibited unique optical properties such as high visible
      reflectance (23.9%) to block blue rays, and excellent near infrared shielding
      efficiency (98.0%), meanwhile it still maintained a high transparency meaning
      that this foil could potentially be applied in energy-saving window films. To sum
      up, this study provides new insight into devising flexible hybrid films with
      novel optical properties, which could be further extended to prepare other
      optical films for potential use in automobile, architectural and other decorative
      fields.

PMID- 29219847
TI  - Strong enhancement of emission efficiency in GaN light-emitting diodes by plasmon
      coupled light amplification of graphene.
AB  - Recently, we have demonstrated that excitation of plasmon-polaritons in a
      mechanically-derived graphene sheet on the top of a ZnO semiconductor
      considerably enhances its light emission efficiency. If this scheme is also
      applied to device structures, it is then expected that the energy efficiency of
      light-emitting diodes (LEDs) increases substantially and the commercial potential
      will be enormous. Here, we report that the plasmon-induced light coupling
      amplifies emitted light by ~1.6 times in doped large-area chemical-vapor
      deposition-grown graphene, which is useful for practical applications. This
      coupling behavior also appears in GaN-based LEDs. With AuCl3-doped graphene on Ga
      doped ZnO films that is used as transparent conducting electrodes for the LEDs,
      the average electroluminescence intensity is 1.2-1.7 times enhanced depending on
      the injection current. The chemical doping of graphene may produce the
      inhomogeneity in charge densities (i.e., electron/hole puddles) or roughness,
      which can play a role as grating couplers, resulting in such strong plasmon
      enhanced light amplification. Based on theoretical calculations, the plasmon
      coupled behavior is rigorously explained and a method of controlling its
      resonance condition is proposed.

PMID- 29219848
TI  - Embedded tin nanocrystals in silicon-an electrical characterization.
AB  - Tin nanocrystals embedded in a SiSn layer grown by molecular beam epitaxy on n
      type Si are investigated by means of deep level transient spectroscopy. Two Sn
      related deep traps are observed, depending on the annealing temperature of the
      samples. A deep level at [Formula: see text] (Sn1) is observed for annealing
      temperatures up to [Formula: see text]C, whereas a level at [Formula: see text]
      (Sn2) appears for annealing temperatures above [Formula: see text]C. Scanning
      transmission electron microscopy shows the formation of Sn nanocrystals at
      [Formula: see text]C, which coincides with the appearance of Sn2. Sn1 is
      tentatively assigned to a Sn related precursor defect, which transforms upon
      annealing into either Sn nanocrystals or an interface defect located at the
      nanocrystal surface.

PMID- 29219849
TI  - Multidirectional flexible force sensors based on confined, self-adjusting carbon
      nanotube arrays.
AB  - We demonstrate a highly sensitive force sensor based on self-adjusting carbon
      nanotube (CNT) arrays. Aligned CNT arrays are directly synthesized on silicon
      microstructures by a space-confined growth technique which enables a facile self
      adjusting contact. To afford flexibility and softness, the patterned
      microstructures with the integrated CNTs are embedded in polydimethylsiloxane
      structures. The sensing mechanism is based on variations in the contact
      resistance between the facing CNT arrays under the applied force. By finite
      element analysis, proper dimensions and positions for each component are
      determined. Further, high sensitivities up to 15.05%/mN of the proposed sensors
      were confirmed experimentally. Multidirectional sensing capability could also be
      achieved by designing multiple sets of sensing elements in a single sensor. The
      sensors show long-term operational stability, owing to the unique properties of
      the constituent CNTs, such as outstanding mechanical durability and elasticity.

PMID- 29219850
TI  - Controlled growth of gold nanocrystals on biogenic As-S nanotubes by galvanic
      displacement.
AB  - Traditional methods for fabricating nanoscale arrays are usually based on
      lithographic techniques while alternative new approaches rely on the use of
      nanoscale templates made of synthetic or biological materials. Here, gold (Au)
      nanocrystals were grown on the surface of the microbiologically formed As-S
      nanotubes through the process of galvanic displacement. The size and organization
      of the synthesized Au nanocrystals were affected by the pH dependent speciation
      of HAuCl4 precursors as well as the initial ratio of As-S/HAuCl4. We found that
      as pH increased, the Au nanocrystals grown on As-S nanotubes had smaller sizes
      but were more likely to assemble in one-dimension along the nanotubes. At a
      proper initial ratio of As-S/HAuCl4, Au nanotubes were formed at pH 6.0. The
      mechanism of Au nanostructures formation and the synthesis process at different
      pHs were proposed. The resulting Au nanoparticle/As-S nanotube and Au nanotube/As
      S nanotube hetero-structures may provide important properties to be used for
      novel nano-electronic devices.

PMID- 29219851
TI  - Oxygen sensitive polymeric nanocapsules for optical dissolved oxygen sensors.
AB  - Immobilization of the oxygen-sensitive probes (OSPs) in the host matrix greatly
      impacts the performance and long-term usage of the optical dissolved oxygen (DO)
      sensors. In this work, fluorescent dyes, as the OSPs, were encapsulated with a
      crosslinked fluorinated polymer shell by interfacial confined reversible addition
      fragmentation chain transfer miniemulsion polymerization to fabricate oxygen
      sensitive polymeric nanocapsules (NCs). The location of fluorescent dyes and the
      fluorescent properties of the NCs were fully characterized by fourier transform
      infrared spectrometer, x-ray photoelectron spectrometer and fluorescent spectrum.
      Dye-encapsulated capacity can be precisely tuned from 0 to 1.3 wt% without self
      quenching of the fluorescent dye. The crosslinked fluorinated polymer shell is
      not only extremely high gas permeability, but also prevents the fluorescent dyes
      from leakage in aqueous as well as in various organic solvents, such as ethanol,
      acetone and tetrahydrofuran (THF). An optical DO sensor based on the oxygen
      sensitive NCs was fabricated, showing high sensitivity, short response time, full
      reversibility, and long-term operational stability of online monitoring DO. The
      sensitivity of the optical DO sensor is 7.02 (the ratio of the response value in
      fully deoxygenated and saturated oxygenated water) in the range 0.96-14.16 mg l-1
      and the response time is about 14.3 s. The sensor's work curve was fit well using
      the modified Stern-Volmer equation by two-site model, and its response values are
      hardly affected by pH ranging from 2 to 12 and keep constant during continuous
      measurement for 3 months. It is believed that the oxygen sensitive polymeric NCs
      based optical DO sensor could be particularly useful in long-term online DO
      monitoring in both aqueous and organic solvent systems.

PMID- 29219852
TI  - Dietary Crocin Reverses Melanoma Metastasis.
AB  - Crocus sativus and its bioactive constituent crocin are well known for anti-tumor
      potential in different models. However, the efficacy of crocin on in-vivo
      melanoma metastasis is not yet reported. In this study, melanoma metastatic model
      was developed by tail vein injection of B16F-10 cells in to C57BL/6 mice.
      Metastatic mice treated with two different doses of crocin (250 and 500 ug/kg of
      bodyweight) for 10 days and parameters such as lung metastasis inhibition, mean
      survival time, lung hydroxyproline, uronic acid and hexosamine levels were
      analyzed after 21 days of treatment. Then blood was collected and serum gamma
      glutamyl transpeptidase (g-GGT), sialic acid, tumor necrosis factor alpha (TNF
      a), interleukin 10 (IL-10), IL-6, IL-2, and TIMP-1 levels were measured. Further,
      a lung histological examination was done in crocin treated metastatic mice.
      Subsequently hallmark metastatic parameters such as matrix metalloproteases
      (MMPs), extracellular regulated kinase 2 (ERK2), vascular endothelial growth
      factor (VEGF), and K-ras gene expression were investigated in the lungs of crocin
      treated metastatic mice. Further, in-vitro adhesion, invasion and migration of
      B16F-10 cells were examined after 24 h of crocin (5 and 10 ug/mL) treatment.
      Administration of crocin to tumor bearing C57BL/6 mice reduced the lung
      metastasis by 85%. Elevated levels of hydroxyproline, uronic acid, hexosamine,
      serum sialic acid andg-GGT in metastatic control were found to be significantly
      reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9,
      ERK-2, K-ras, and VEGF. Crocin reduced the ability of B16F-10 cells invasion
      (p<0.05), migration (p<0.05) and adhesion by upregulating E-cadherin expression.
      In conclusion, crocin elicited marked anti-metastatic potential by regulating the
      metastasis induced biomarkers.

PMID- 29219853
TI  - Effects of a soybean milk product on feto-neonatal development in rats.
AB  - Since estrogenic pollutants and phytoestrogens can cause the disorder of the
      reproductive system, the effects of a soybean milk product (Vegemil<sup>(r)</sup>
      containing 162 ppm isoflavones) on the feto-neonatal development, including male
      reproductive function, were investigated. Pregnant rats were fed the soybean milk
      (5% or 100% in drinking water) from gestational day (GD) 6 to parturition or to
      post-natal day (PND) 56. Specifically, the rats were divided into 4 groups: the
      control group (drinking water), the GD5% group (5% soybean milk during only the
      GD period), the GD-PND5% group (5% soybean milk during the GD and PND periods),
      and the GD-PND100% group (100% soybean milk instead of water during the GD and
      PND periods). During the gestational, lactational, and developmental periods, the
      reproductive and developmental parameters of dams and offspring were observed.
      Feeding soybean milk did not affect the birth and physical development of both
      male and female offspring. At PND57, the weights of the testes and epididymides
      of F1 males significantly increased by feeding a high concentration of the
      soybean milk (GD-PND100%). In addition, feeding of the soybean milk during both
      the GD and PND periods (GD-PND5% and GD-PND100%) enhanced the sperm counts and
      motility. The results indicate that soybean milk is safe for embryos, fetuses,
      and offspring, and improves the post-generational development of male
      reproductive function.

PMID- 29219854
TI  - Reconstruction of the Scapula in Pediatric and Adolescent Patients After Total
      Scapulectomy. A Report of 10 Patients Treated by Extracorporeal Irradiation and
      Reimplantation of the Scapula.
AB  - BACKGROUND: Ewing sarcoma of the scapula is uncommon. Restoration of shoulder
      function after total scapulectomy is challenging. Extracorporeal irradiation and
      reimplantation is a well-known method of biological reconstruction in orthopaedic
      oncology; yet very few reports in the literature describe its specific use in
      tumors of the scapula. PATIENTS AND METHODS: Ten patients with the diagnosis of
      Ewing sarcoma of the scapula were surgically treated by total scapulectomy and
      extracorporeal irradiation and reimplantation of the scapula. The mean age at
      presentation was 10 years (3 to 15 y). Six patients were male individuals and 4
      were female individuals. An extracorporeal single dose of 5000 cGy was applied to
      each graft. At reimplantation, internal fixation was used in the first 2 cases,
      whereas, in the following 8 patients, stabilization was carried out by resuturing
      of the glenohumeral and acromioclavicular joint capsules without internal
      fixation. An ipsilateral Latissimus Dorsi muscle flap was used in all patients to
      cover the irradiated scapula. RESULTS: The mean follow-up duration was 29.2
      months (13 to 50 m). At the latest follow-up, 8 patients were continuously
      disease free and 2 patients had systemic relapse. No patient had local
      recurrence. The mean musculoskeletal tumor society functional score was 87%
      (66.6% to 100%). Eight of the 10 patients (80%) could actively elevate the upper
      limb up to and beyond 90 degrees in both the forward and scapular planes.
      Complications included wound gaping in 2 patients (20%), dislocation of the
      acromioclavicular joint in 3 patients (30%), and partial resorption of the
      scapular graft in 5 patients (50%). No patient showed any progressive
      deterioration of his or her shoulder function throughout the follow-up period.
      CONCLUSIONS: The irradiated scapular graft provides a stable biological fulcrum
      for the reattached muscles of the shoulder joint after total scapulectomy,
      thereby providing an adequate postoperative range of shoulder elevation. A longer
      follow-up study is needed to evaluate the progression and effect of graft
      resorption on the functional outcome. LEVEL OF EVIDENCE: Level IV.

PMID- 29219855
TI  - Determining Hinge Abduction in Legg-Calve-Perthes Disease: Can We Reliably Make
      the Diagnosis?
AB  - BACKGROUND: Although hinge abduction is recognized as an important finding in
      children with Legg-Calve-Perthes disease, variable diagnostic criteria exist. The
      purpose of this study was (1) to test the interobserver and intraobserver
      agreement of the current definition of hinge abduction and (2) to develop
      consensus regarding key diagnostic features that could be used to improve our
      diagnostic criteria. METHODS: Four orthopaedic surgeons with subspecialty
      pediatric hip interest independently assessed 30 randomly ordered cases of Legg
      Calve-Perthes disease. Each case included 2 fluoroscopic images of hip
      arthrograms (anteroposterior and abduction views). Surgeons graded the cases in a
      binary manner (hinge/no-hinge) on 2 separate occasions separated by a 4-week
      interval. Following reliability testing and comprehensive review of the
      literature, consensus-building sessions were conducted to identify key diagnostic
      features. Surgeons then regraded a new series of cases. Interobserver and
      intraobserver agreement between first/second and third/fourth readings were
      assessed using the Fleiss kappa. RESULTS: Interobserver kappa for hinge abduction
      between the first and second surveys was 0.52 (with 0.41 to 0.60 considered
      moderate agreement), compared with 0.56 for the third and fourth surveys. First
      and second reading intraobserver agreement ranged from 0.59 to 0.83 compared with
      0.75 to 1.00 for third and fourth reading. Consensus sessions identified several
      key diagnostic factors including: adequate visualization of the labral contour
      and ability of the lateral epiphysis to slip below the chondrolabral complex in
      abduction. Medial dye pooling, often due to asphericity of the femoral head, was
      not found to be a useful diagnostic criterion. CONCLUSIONS: Despite a combined
      experience of over 70 years among the reviewers, we found just slightly better
      than 50:50 agreement in what constitutes hinge abduction. Consensus discussions
      did improve our agreement but these modest changes emphasize how difficult it is
      to develop reliable diagnostic criteria for hinge abduction. As a result, we
      caution against using hinge abduction as an inclusion criteria or outcome measure
      for research purposes, as the diagnostic agreement can be inconsistent. LEVEL OF
      EVIDENCE: Level III-diagnostic study.

PMID- 29219856
TI  - The Interaction of Depressive Symptoms and Hazardous Drinking in Relation to
      Tobacco Craving Among Treatment Seeking Depressed Smokers: Sex Differences.
AB  - OBJECTIVES: The present study sought to address whether there is sex effect in
      the interactive effect between depressive symptoms and hazardous drinking in the
      prediction of smoking craving after cognitive-behavioral smoking cessation
      treatment among those with at least mild depression. METHODS: Participants (n =
      114, mean age 42.0, SD = 9.73, 64% women) were treatment-seeking smokers who
      attended 6 weekly 1-hour sessions involving psychological treatment for
      cessation. Participants reported depressive symptoms and alcohol use at baseline
      and reported craving at baseline and after treatment. RESULTS: Results indicated
      that there was a statistically significant 3-way interaction (depression by
      alcohol use by sex) for smoking craving (B = -0.30, standard error [SE] = 0.14, P
      = 0.042) and appetitive craving (B = -.21, SE = 0.09, P = 0.031), but not
      negative reinforcement craving. The form of the significant interactions indicted
      that higher levels of depressive symptoms and alcohol use were related to greater
      levels of craving at the end of treatment only among men. CONCLUSIONS: The
      current findings provide novel empirical evidence suggesting that there is a
      clinically relevant interplay between depressive symptoms and alcohol use
      regarding general craving and appetitive craving among male treatment-seeking
      smokers. Although the present results should be replicated in larger samples,
      this type of research can inform the development of sex-specific interventions
      for smoking cessation.

PMID- 29219857
TI  - A Literature Review of Percutaneous Endoscopic Gastrostomy: Dealing With
      Complications.
AB  - Sufficient energy and essential nutrients are vital for normal growth and
      development in childhood. Ideally, nutrition should be provided orally. However,
      if the gastrointestinal system is functional, enteral tube feeding can be used
      when nutritional requirements cannot be provided orally, thus providing
      nutritional benefits and enabling positive disease management in pediatric
      patients. Postoperative care in children allows monitoring of the position and
      functionality of the tube; performing nutrition intolerance, growth, hydration,
      and nutritional assessments; and performing metabolic and complication follow
      ups. Tube feeding in pediatric patients is beneficial and has positive effects in
      controlling and managing diseases and providing appropriate nutrition in
      children. However, in postoperative patients, it is important to prevent
      potential complications, which can be classified into 5 groups: mechanical,
      gastrointestinal, metabolic, infectious, and pulmonary complications. Important
      points for managing complications include having enteral nutrition practices
      based on evidence-based guidelines, sharing outcomes with nurses working in
      clinical settings, creating enteral feeding guides in clinical settings,
      providing patients/patients' family with training in line with these guides, and
      maintaining follow-ups at home. This literature review discusses complications
      and practices regarding the management of complications after percutaneous
      endoscopic gastrostomy.

PMID- 29219858
TI  - The Precision of eCAP Thresholds Derived From Amplitude Growth Functions.
AB  - OBJECTIVE: An amplitude growth function (AGF) shows the amplitude of an
      electrically evoked compound action potential (eCAP) as a function of the
      stimulation current. AGFs can be used to derive the eCAP threshold, which
      represents the minimum amount of current needed to elicit a measurable eCAP. eCAP
      thresholds have been widely used clinically to, for example, assist with sound
      processor programming. However, no eCAP precision has been included to date. The
      aim of this study was to investigate the precision of eCAP thresholds and
      determine whether they are precise enough for clinical use. DESIGN: The study is
      retrospective, and the data comprised 826 AGFs, intraoperatively measured in 111
      patients implanted with a HiRes90K cochlear implant (Advanced Bionics). For each
      AGF, the eCAP threshold was determined using two commonly used methods: linear
      extrapolation (LE) toward the x axis and detection of the last visible (LV) eCAP.
      Subsequently, the threshold confidence interval (TCI) of each eCAP threshold was
      calculated to serve as a metric for precision, whereby a larger TCI means a lower
      precision or reliability. Additionally, the eCAP thresholds results were compared
      with most recent behavioral fitting thresholds (T profile) to put the eCAP
      threshold analysis in clinical context. Thereby, the association between eCAP and
      behavioral thresholds was calculated, both for all subjects together (group
      analysis) and, in contrast to previous studies, within individual subjects.
      RESULTS: Our data show that the TCIs were larger with the LE method than with the
      LV method. The eCAP thresholds estimated by the LE method were systematically
      smaller than those estimated by the LV method, while the LE thresholds with the
      smallest TCIs correlated best with the LV thresholds. Correlation analysis
      between eCAP and behavioral thresholds revealed correlation coefficients of r =
      0.44 and r = 0.54 for the group analysis of LE and LV thresholds, respectively.
      Within individual subjects, however, the correlation coefficients varied from
      approximately -1 to +1 for both LE and LV thresholds. Further analysis showed
      that across subjects, the behavioral thresholds fell within the TCIs of the eCAP
      threshold profiles. CONCLUSION: This study shows that eCAP thresholds have an
      uncertainty that can be estimated using TCIs. The size of the TCI depends on
      several factors, for example, the threshold estimation method and measurement
      conditions, but it is often larger than one would expect when just looking at the
      threshold values. Given these large TCIs, future research on eCAP thresholds
      should be accompanied by a measure of precision to correctly apply eCAP
      thresholds in clinical practice. Comparing our eCAP threshold results with T
      profiles indicates that the eCAP thresholds are possibly not precise enough to
      predict T profiles.

PMID- 29219859
TI  - In Search of Mobile Applications for Patients With Pelvic Floor Disorders.
AB  - OBJECTIVES: The aims of the study were to identify patient-centered applications
      (apps) in female pelvic medicine and reconstructive surgery and to evaluate them
      using a modified APPLICATIONS scoring system. METHODS: A comprehensive list of
      female pelvic medicine and reconstructive surgery search terms was used to
      identify apps in the iTunes store. Apps that were eligible for scoring were in
      English, pertinent to the search term, patient centered, and accurate. All five
      authors independently evaluated eligible apps using a modified APPLICATIONS
      scoring system and subsequently reconciled differences by discussion. RESULTS:
      One hundred and fifty-seven terms were generated and searched in the iTunes Store
      to reveal 4127 apps. Twenty-three eligible apps were scored. Approximately half
      (47%, 11/23) of the apps were free. Twelve (52%) apps cited scientific literature
      or expert source. Only 8 (35%) of the apps were also available in the Google Play
      Store. "Squeezy," "LeakFreeMe," and "Stop UTI" received the highest score of 14.
      CONCLUSIONS: Few identified apps were accurate and subsequently scored. Our
      results demonstrate that when searching for apps, patients are likely to obtain
      information that is not relevant or inaccurate, even if the appropriate search
      term is used. By carefully excluding inaccurate apps, providers should feel
      confident that the 23 scored apps can be shared with patients.

PMID- 29219860
TI  - How Change Catches Fire.

PMID- 29219861
TI  - Sacrocolpopexy With Concomitant Total vs Supracervical Hysterectomy: Functional
      Support Comparisons in Cadavers.
AB  - OBJECTIVE: This study aimed to compare the ability of abdominal sacrocolpopexy
      (ASC) with concomitant total vs supracervical hysterectomy to resist downward
      traction as a measure of functional anatomic support in human cadavers. METHODS:
      Supracervical hysterectomy was performed on unembalmed cadaver specimens,
      followed by ASC attaching polypropylene mesh to the posterior cervix/vagina only
      and then the anterior and posterior cervix/vagina. Using a metal bolt placed
      through the cervix tied to a filament passing through a fixed pulley system,
      successive weights of 0.5 to 3.0 kg were added to provide increasing loads on the
      apex (cervix), and the distances traversed by the apex were recorded. The same
      process was then repeated in each specimen after removal of the cervix (with
      vaginal cuff closure). One-way and repeated-measures analysis of measure was used
      for between-group and within-group comparisons, respectively, with P <= 0.05
      considered statistically significant. RESULTS: Eight cadavers were examined. At
      lower weight loads, pulling distances in the 4 groups examined were similar and
      were not significantly different with the presence or absence of the cervix. At
      weight loads of 2.5 kg or greater, we noted a trend of increased pulling
      distances when posterior mesh only was used vs when anterior/posterior mesh was
      placed, although this difference was not significant. Interestingly, there was
      tearing of the vaginal wall or partial separation of mesh/sutures attachments to
      the vagina noted in 3 specimens. CONCLUSIONS: This study showed no differences in
      the ability of the cervix (after supracervical hysterectomy) compared with the
      vaginal cuff (after total hysterectomy) to resist downward traction of successive
      weights after ASC. Clinical trials are necessary to correlate these findings with
      prolapse recurrence rates and patient satisfaction following these procedures.

PMID- 29219862
TI  - When Can We Predict the Outcome of an Electroconvulsive Therapy Course in
      Adolescents?: A Retrospective Study.
AB  - OBJECTIVE: There is a dearth of up-to-date literature regarding electroconvulsive
      therapy (ECT) in adolescents, and the question of when to pronounce course
      failure has not been properly addressed. The current study aims to evaluate
      trajectories of clinical status throughout ECT courses in adolescent patients.
      METHODS: We retrieved detailed data of 36 patients who received ECT in our
      treatment center. Clinical records were retrospectively assessed and evaluated
      every 6 ECT sessions to quantify Clinical Global Impressions-Improvement (CGI-I)
      scores. RESULTS: The mean number of sessions per course was 24.4 +/- 14.2. The
      mean CGI-I score at the conclusion of the ECT courses was 2.47 +/- 1.19. At the
      end of the acute treatment stage, 26 patients (72.2%) were much or very much
      improved, based on CGI-I scores. Only 5 patients exhibited a significant response
      after 6 sessions or fewer, whereas 21 patients (56.6%) improved after 12
      sessions. Pearson correlations between CGI-I scores throughout the course of ECT
      showed no significant correlation between CGI-I scores after 6 sessions and the
      final CGI-I scores. However, a significant correlation was found between CGI-I
      scores after 12 sessions and the final CGI-I score. CONCLUSIONS: An improvement
      in the clinical status of adolescents treated by ECT might occur only after a
      substantial number of sessions. An early lack of response does not necessarily
      predict a failed ECT course.

PMID- 29219863
TI  - The challenges of evidence implementation: it's all about the context.

PMID- 29219864
TI  - Characteristics and processes of clinical reasoning in nurses and factors related
      to its use: a scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objectives of the scoping review are to.

PMID- 29219865
TI  - Impact of male partner involvement on modern contraceptive use among married or
      partnered women in developing countries: a protocol for systematic review.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this systematic review is to explore
      the impact of male partner involvement on modern contraceptive use among married
      or partnered women of reproductive age in developing countries. Specifically,
      does male partner involvement.

PMID- 29219866
TI  - Educational interventions that address handover skills of healthcare
      professionals: a scoping review protocol.
AB  - OBJECTIVES: The objective of this scoping review is to identify, organize and
      present existing literature on training interventions on handovers for healthcare
      professionals to highlight the existing gaps in evidence to inform future
      research in this field. More specifically the objectives are to.

PMID- 29219867
TI  - Interventions and programs that support the health and development of infants
      with prenatal alcohol and/or drug exposure in foster care: a scoping review
      protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to identify
      and describe caregiving interventions and program elements that support the
      health and development of infants with prenatal alcohol and/or drug exposure in
      foster care.

PMID- 29219868
TI  - Experiences of healthcare middle managers in developing capacity and capability
      to manage complexity: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this review is to explore the
      experiences of healthcare middle managers in developing capacity and capability
      to manage in a leadership role characterized by high complexity.

PMID- 29219869
TI  - Comparison of vegetarian versus animal-based low protein diets on estimated
      glomerular filtration rates in chronic kidney disease patients: a systematic
      review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this review is to evaluate studies
      to determine the effect of a low-protein, vegetarian diet as compared to a low
      protein, animal-based diet on estimated glomerular filtration rates (eGFR) in
      adults with chronic kidney disease (CKD).

PMID- 29219870
TI  - Registered nurse experiences of nursing professional identity: a qualitative
      systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise
      and synthesize the best available evidence related to registered nurses'
      experiences of nursing professional identity in nursing care settings.

PMID- 29219871
TI  - Reflection in the training of nurses in clinical practice settings: a scoping
      review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: This scoping review will seek to find answers for the
      following questions which will focus on the use of reflection in the education of
      nurses in clinical settings:The review will also extract and map data regarding:
      i) what outcomes have been found in relation to the use of different tools and
      approaches (e.g. dialogues, diaries, case studies); ii) how approaches and tools
      have been implemented as interventions; iii) details of the topic or focus of
      reflection (e.g. ethical issues, care of older adults etc.); iv) details about
      the participants involved in reflection activities (e.g. first or second year
      undergraduate nursing students etc.); and v) barriers/challenges to the use of
      reflection approaches/tools. Additional details may also be extracted and mapped
      during the process of the scoping review and this will be explained in the final
      scoping review report.

PMID- 29219872
TI  - Effectiveness of decision aids on smoking cessation in adult patients: a
      systematic review protocol.
AB  - REVIEW QUESTION: The objective of this review is to determine the effectiveness
      of the use of decision aids in a shared decision-making encounter between any
      healthcare provider and adult patients who smoke, compared to standard education
      on smoking cessation, in any healthcare setting.Specifically, the review
      questions are: What is the effectiveness of the use of decision aids in a shared
      decision-making encounter in any healthcare setting between the healthcare
      provider and adult patients who smoke compared to standard education, based on
      the patient's.

PMID- 29219873
TI  - Efficacy and harms of pharmacological interventions for neurobehavioral symptoms
      in post traumatic amnesia after traumatic brain injury: a systematic review and
      meta-analysis protocol.
AB  - REVIEW OBJECTIVE/QUESTION: The objective of this systematic review is to
      synthesize the best available evidence on the effectiveness and harms of
      pharmacotherapy as compared to all types of comparators for the management of
      neurobehavioral symptoms in post-traumatic amnesia in adults aged 16 years and
      over who have sustained a traumatic brain injury. This review forms part of a
      larger project which aims to gather the evidence for the pharmacological
      treatment of neurobehavioral symptoms post traumatic brain injury as a prelude to
      the development of a clinical guideline.

PMID- 29219874
TI  - Experiences of community-dwelling older adults with the use of telecare in home
      care services: a qualitative systematic review.
AB  - BACKGROUND: The aging population will lead to a rise in the number of people with
      age-related diseases, and increasing demand for home care services. Telecare is
      seen as a solution to this challenge by promoting aging in place. Nevertheless,
      there is still a poor understanding of older adults' experiences with the actual
      use of telecare. OBJECTIVE: The aim of this review was to identify and synthesize
      the best available qualitative evidence of community-dwelling older adults'
      experience with the use of telecare in home care services. INCLUSION CRITERIA:
      This review considered studies that focused on qualitative data, examining older
      adults' experiences with the use of active and passive technology devices, such
      as personal alarms and sensor technology, in the context of home care services.
      SEARCH STRATEGY: This review systematically searched the databases Scopus,
      CINAHL, PsycINFO, and SveMed+ to find both published and unpublished studies in
      English, Norwegian, Swedish and Danish, from 2005 to 2017. METHODOLOGICAL
      QUALITY: Methodological quality of the included studies was assessed
      independently by two reviewers using the Joanna Briggs Institute Qualitative
      Assessment and Review Instrument. DATA EXTRACTION: Qualitative data were
      extracted from papers included in the review using the standardized Qualitative
      Assessment and Review Instrument from the Joanna Briggs Institute. DATA
      SYNTHESIS: Qualitative research findings were pooled using the Joanna Briggs
      Institute Qualitative Assessment and Review Instrument, and involved aggregation
      and synthesis of findings. RESULTS: A total of 118 findings from 11 studies were
      aggregated into 20 categories. The categories generated seven synthesized
      findings: 1) Aging in place is desired; however, it may also be related to
      feeling isolated and lonely. 2) Telecare contributes to safety, security, and
      aging in place. 3) Privacy is not seen as a problem by most older adults because
      the technology is intended to help them live safely in their own home. 4) Some
      telecare devices have side effects, especially new technology. Some devices do
      not work outside the home, thus limiting active aging. 5) Some older adults
      experience a misfit between technology and needs. They must see the value of a
      telecare device to use it. 6) Telecare may enforce an identity with negative
      connotations on older adults, as frail and helpless people. Autonomy is
      considered important. 7) Lack of understanding can hamper the correct use of
      telecare. Specific strategies may be needed. CONCLUSIONS: The experiences with
      the use of telecare are diverse. Findings indicate telecare systems can promote
      safety and security to age in place that is a wish of many older adults. However,
      "one size does not fit all"- Telecare systems must fit individual needs, and be
      supported by service providers to accommodate sustainable use over time.

PMID- 29219875
TI  - eHealth interventions for parents in neonatal intensive care units: a systematic
      review.
AB  - BACKGROUND: As technology becomes increasingly more advanced, particularly video
      technology and interactive learning platforms, some neonatal intensive care units
      are embracing electronic health (eHealth) technologies to enhance and expand
      their family-centered care environments. Despite the emergence of eHealth, there
      has been a lack of systematic evaluation of its effectiveness thus far.
      OBJECTIVES: To examine the effect of eHealth interventions used in neonatal
      intensive care units on parent-related and infant outcomes. INCLUSION CRITERIA
      TYPES OF PARTICIPANTS: This review considered studies that included parents or
      primary caregivers of infants requiring care in a neonatal intensive care unit.
      TYPES OF INTERVENTION(S): This review considered studies that evaluated any
      eHealth interventions in neonatal intensive care units, including education (e.g.
      web-based platforms, mobile applications); communication (e.g. videos, SMS or
      text messaging), or a combination of both. Comparators included no eHealth
      interventions and/or standard care. TYPES OF STUDIES: Experimental and
      epidemiological study designs including randomized controlled trials, non
      randomized controlled trials, quasi-experimental, before and after studies,
      prospective and retrospective cohort studies, case-control studies, and
      analytical cross sectional studies were considered. OUTCOMES: This review
      considered studies that included parent-related outcomes (use and acceptance,
      stress/anxiety, confidence, financial impact, satisfaction and technical issues)
      and neonatal outcomes (length of stay, postmenstrual age at discharge, parental
      presence and visits). SEARCH STRATEGY: A systematic search was undertaken across
      four databases to retrieve published studies in English from inception to
      November 18, 2016. METHODOLOGICAL QUALITY: Critical appraisal was undertaken by
      two independent reviewers using standardized critical appraisal instruments from
      the Joanna Briggs Institute System for the Unified Management, Assessment and
      Review of Information (JBI-SUMARI). DATA EXTRACTION: Quantitative data were
      extracted from included studies independently by two reviewers using the
      standardized data extraction tool from JBI-SUMARI. DATA SYNTHESIS: A
      comprehensive meta-analysis for all outcomes was not possible and data has been
      reported narratively for all outcomes. RESULTS: Eight studies met inclusion
      criteria and were included in the review. The majority of the studies were low to
      very low quality. The study design and type of eHealth technology examined varied
      greatly. There appears to be growing interest in the topic as over half of the
      included studies were published within the past two years. Primary findings
      suggest parent acceptance and use of eHealth interventions but an unclear impact
      on neonatal outcomes, particularly on length of stay, a commonly reported
      neonatal outcome. Due to the variation in eHealth interventions, and
      heterogeneity across studies, meta-analysis was not possible. Numerous single
      studies and small sample sizes limited the degree of adequate strength to
      determine statistical differences across outcomes. CONCLUSIONS: While
      heterogeneity across studies precluded meta-analysis, consistent trends across
      all studies examining parental acceptance of eHealth interventions indicate that
      parents are willing to accept eHealth interventions as part of their neonatal
      intensive care, suggesting that the incorporation and evaluation of eHealth
      interventions in the neonatal intensive care unit setting is warranted. Further
      high quality studies are needed with larger sample sizes to detect changes in
      outcomes. As eHealth intervention studies move beyond feasibility and
      implementation, there is a demand for randomized control trials to examine the
      effect of eHealth interventions on parent and neonatal outcomes compared to usual
      care. Future studies should consider reporting of outcomes using standardized
      measures which would allow comparison across eHealth interventions in subsequent
      reviews.

PMID- 29219876
TI  - Effectiveness of patient-centered interventions on falls in the acute care
      setting compared to usual care: a systematic review.
AB  - BACKGROUND: Unintentional falls during hospitalization remain a concern for
      healthcare institutions globally despite implementation of various improvement
      strategies. Although the incidence of falls has been of heightened focus for many
      years and numerous studies have been done evaluating different approaches for
      fall prevention, fall rates remain high in acute care settings. Patient fall risk
      scales tend to address only particular intrinsic and extrinsic factors but do not
      adequately assess a patient's current fall risk status, subsequently warranting
      more patient-centered risk assessments and interventions. OBJECTIVES: To evaluate
      the effectiveness of patient-centered interventions on falls in the acute care
      setting. INCLUSION CRITERIA TYPES OF PARTICIPANTS: All adult patients admitted to
      medical or surgical acute care units for any condition or illness. TYPES OF
      INTERVENTION(S): Patient-centered intervention strategies to reduce falls
      compared to usual care. TYPES OF STUDIES: Randomized control trials. TYPES OF
      OUTCOMES: Primary outcome: fall rates or number of falls. Secondary outcome: fall
      related injuries. SEARCH STRATEGY: A comprehensive search strategy aimed to find
      relevant published and unpublished quantitative, English language studies from
      the inception of databases through July 30, 2016 was undertaken. Databases
      searched included: PubMed, CINAHL, Embase and Health Source: Nursing/Academic
      Edition. A search for unpublished studies was also performed using ProQuest
      Dissertations and Theses, the New York Academy of Medicine and the Virginia
      Henderson e-Repository. METHODOLOGICAL QUALITY: Reviewers evaluated the included
      studies for methodological quality using the standardized critical appraisal
      instrument form from the Joanna Briggs Institute. DATA EXTRACTION: Quantitative
      data were extracted from papers included in the review using the standardized
      data extraction form from the Joanna Briggs Institute. DATA SYNTHESIS: Due to
      clinical and methodological heterogeneity among the included studies, a meta
      analysis was not possible. The findings of this review have been presented in
      narrative form. RESULTS: Five randomized control trials were included. Three
      studies demonstrated statistically significant reductions in fall rates (p <
      0.04) while two studies showed no difference in fall rates between groups (p >
      0.5). In the three studies that demonstrated reduced fall rates, personalized
      care plans and patient-centered education based on patients' fall risk results
      were utilized. Three studies measured the secondary outcome of fall-related
      injuries; however, results demonstrated no difference in fall-related injuries
      between groups (p > 0.5). CONCLUSIONS: Evidence of this review indicates patient
      centered interventions in addition to tailored patient education may have the
      potential to be effective in reducing falls and fall rates in acute care
      hospitals. There is limited high quality evidence demonstrating the effectiveness
      of patient-centered fall prevention interventions so novel solutions are urgently
      needed and warrant more rigorous, larger scale randomized trials for more robust
      estimates of effect.

PMID- 29219877
TI  - Effectiveness of robotic assisted rehabilitation for mobility and functional
      ability in adult stroke patients: a systematic review.
AB  - BACKGROUND: Stroke is a leading cause of long-term disability, and
      rehabilitation, involving repetitive, high intensity, task-specific exercises, is
      the pathway to restoring motor skills. Robotic assistive devices are increasingly
      being used and it is hoped that with robotic devices, rehabilitation progress can
      be achieved for patients. OBJECTIVES: To examine the effectiveness of robotic
      devices in the rehabilitation of stroke patients for upper limb mobility, lower
      limb mobility, and activities of daily living. The sustainability of treatment
      effect was also examined. INCLUSION CRITERIA TYPES OF PARTICIPANTS: Adult stroke
      patients 18 years and over. TYPES OF INTERVENTION(S): Rehabilitation of stroke
      patients using robotic devices with assistive automation, compared to
      conventional physiotherapy. OUTCOMES: Motor movements of upper limbs, walking
      movement of lower limbs and activities of daily living, including follow-up
      measurements to examine the sustainability of treatment effect. TYPES OF STUDIES:
      Randomized and controlled clinical trials. SEARCH STRATEGY: Published and
      unpublished studies in English were searched. METHODOLOGICAL QUALITY: All studies
      meeting the review inclusion criteria were independently assessed for
      methodological quality by two reviewers. DATA EXTRACTION: Quantitative data were
      extracted using the standardized data extraction tool from the Joanna Briggs
      Institute Meta-Analysis of Statistics Assessment and Review Instrument. DATA
      SYNTHESIS: Quantitative data were pooled in statistical meta-analysis. Effect
      sizes expressed as standardized mean difference, 95% confidence intervals and
      levels of heterogeneity (I) were calculated. Where statistical pooling was not
      possible, the findings were presented in narrative form. RESULTS: Fifty-one
      studies with 1798 patients were included in this review. Thirty studies examined
      upper limb interventions and 21 studies evaluated lower limb gait training. Non
      significant results were found for upper limb (SMD 0.07, 95% CI -0.11 to 0.26, I
      = 41%, P = 0.45), lower limb (SMD 0.17, 95% CI -0.15 to 0.48, I = 75%, P = 0.31)
      and activities of daily living (SMD 0.11, 95% CI -0.11 to 0.33, I = 66%, P =
      0.32). For patients with severely impaired lower limbs, a significant difference
      was observed in favor of robotics (SMD 0.41, 95% CI 0.19 to 0.63, I = 28%, P =
      0.0003). P-value analysis did not show significant results for the sustainability
      of treatment effect post intervention. CONCLUSIONS: Robotic training is just as
      effective as conventional training for upper limb motor movement, lower limb
      walking mobility and for activities of daily living. For lower limb patients with
      severe impairment, robotic training produces better outcomes than conventional
      training. The sufficient quantity of studies included and the reasonable quality
      of Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      evidence support the findings.For treatment sustainability of upper and lower
      limbs, robotic training is just as effective as conventional training. However,
      the low quality of GRADE evidence and the lower number of studies included
      require caution for this finding. For treatment sustainability of activities of
      daily living, the better quality of GRADE evidence and the larger number of
      studies analyzed indicate that robotic training is just as effective as
      conventional training.

PMID- 29219878
TI  - Community-based management of multiple drug resistant tuberculosis in a tertiary
      hospital in Tanzania: a best practice implementation project.
AB  - BACKGROUND: The World Health Organization (WHO) has prioritized collaboration
      with communities in its 2016 "End TB" implementation strategy. Acknowledging the
      difficulties that some communities face in gaining access to health facilities
      due to barriers such as stigma, discrimination, healthcare expenditure, transport
      and income loss, partnering with communities in the roll-out of community-based
      TB management activities is vital. AIM: The aim of this project was to make a
      contribution to promoting evidence-based practice with regards to the community
      based management of multidrug-resistant tuberculosis (MDR-TB) at Kibong'oto
      National Infectious Disease Hospital, Tanzania, and thereby supporting
      improvements in patient outcomes and resource utilization. METHODS: The project
      utilized the Joanna Briggs Institute Practical Application of Clinical Evidence
      System (JBI PACES) program to facilitate the collection of pre- and post-audit
      data. The Getting Research into Practice (GRiP) module was also used to analyze
      the potential barriers and for designing the final action plan. This project was
      conducted in three phases over a three-month period at the MDR-TB unit in a
      referral hospital in Northern Tanzania. RESULTS: The project showed that there
      were significant improvements in compliance rates in staff education and
      documentation of patients' suitability and preferences in receiving community
      based care for MDR-TB. The compliance rate of criterion 2, which was already 100%
      at baseline, was slightly lower at follow-up. CONCLUSIONS: The project achieved
      significant improvements in the delivery of evidence-based practice with regards
      to community-based management of MDR-TB.

PMID- 29219879
TI  - Influence of the alkylating function of aldo-Ifosfamide on the anti-tumor
      activity.
AB  - The present work investigates the influence of different DNA damages caused by
      different isophosphoramide mustards on the 3-hydroxypropanal-assisted apoptotic
      antitumor activity of oxazaphosphorine cytostatics using I-aldophosphamide
      perhydrothiazine (IAP) and mesyl-I-aldophosphamide-perhydrothiazine (SUM-IAP) for
      in-vitro and in-vivo experiments. IAP and SUM-IAP hydrolyze spontaneously to the
      corresponding I-aldophosphamide derivatives. They differ in the chemical
      structure of the alkylating moiety, whereas IAP has two chlorethyl groups in the
      SUM-IAP molecule, one chlorethyl group is substituted by a mesylethyl group. With
      both substances, cytotoxicity studies on P388 tumor cells in vitro and therapy
      experiments in mice bearing advanced growing P388 tumors were carried out. IAP
      was significantly more cytotoxic in-vitro than SUM-IAP, but the antitumor
      activity of SUM-IAP was by order of magnitude higher than the antitumor activity
      of IAP. The reason for these findings is discussed with respect to the enzymatic
      cleavage of the various I-aldophosphamide derivatives to the corresponding
      isophosphoramide mustards and 3-hydroxypropanal. Overall, the findings indicate
      that antitumor activity of ifosfamide and derivatives of ifosfamide can be
      improved considerably by altering the alkylating moiety of the molecule, but
      retaining the aldophosphamide structure.

PMID- 29219880
TI  - The Health Information Technology Competencies Tool: Does It Translate for
      Nursing Informatics in the United States?
AB  - Information technology use in healthcare delivery mandates a prepared workforce.
      The initial Health Information Technology Competencies tool resulted from a 2
      year transatlantic effort by experts from the US and European Union to identify
      approaches to develop skills and knowledge needed by healthcare workers. It was
      determined that competencies must be identified before strategies are
      established, resulting in a searchable database of more than 1000 competencies
      representing five domains, five skill levels, and more than 250 roles. Health
      Information Technology Competencies is available at no cost and supports role- or
      competency-based queries. Health Information Technology Competencies developers
      suggest its use for curriculum planning, job descriptions, and professional
      development.The Chamberlain College of Nursing informatics research team examined
      Health Information Technology Competencies for its possible application to our
      research and our curricular development, comparing it originally with the TIGER
      based Assessment of Nursing Informatics Competencies and Nursing Informatics
      Competency Assessment of Level 3 and Level 4 tools, which examine informatics
      competencies at four levels of nursing practice. Additional analysis involved the
      2015 Nursing Informatics: Scope and Standards of Practice. Informatics is a
      Health Information Technology Competencies domain, so clear delineation of
      nursing-informatics competencies was expected. Researchers found TIGER-based
      Assessment of Nursing Informatics Competencies and Nursing Informatics Competency
      Assessment of Level 3 and Level 4 differed from Health Information Technology
      Competencies 2016 in focus, definitions, ascribed competencies, and defined
      levels of expertise. When Health Information Technology Competencies 2017 was
      compared against the nursing informatics scope and standards, researchers found
      an increase in the number of informatics competencies but not to a significant
      degree. This is not surprising, given that Health Information Technology
      Competencies includes all healthcare workers, while the TIGER-based Assessment of
      Nursing Informatics Competencies and Nursing Informatics Competency Assessment of
      Level 3 and Level 4 tools and the American Nurses Association Nursing
      Informatics: Scope and Standards of Practice are nurse specific. No clear cross
      mapping across these tools and the standards of nursing informatics practice
      exists. Further examination and review are needed to translate Health Information
      Technology Competencies as a viable tool for nursing informatics use in the US.

PMID- 29219882
TI  - Concordance of Motion Sensor and Clinician-Rated Fall Risk Scores in Older
      Adults.

PMID- 29219881
TI  - Nursing Knowledge and the 2017 Big Data Science Summit: Power of Partnership,
      Imaging, Impact.

PMID- 29219883
TI  - Zika Virus and the Rio Olympic Games.
AB  - OBJECTIVE: To evaluate the impact of Zika virus on preparation and management of
      the New Zealand (NZ) Olympic team. DESIGN: Descriptive manuscript. SETTING: New
      Zealand Olympic Health team preparation and management during the Rio de Janeiro
      Olympic Games, 2016. PATIENTS (OR PARTICIPANTS): New Zealand Olympic Team
      members. INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS): This manuscript describes
      the approaches used by the NZ Olympic Health team to the minimization of risk
      from Zika virus. MAIN OUTCOME MEASURES: Although descriptive of approach forms
      most of the article, the results of Zika virus serology are presented. RESULTS:
      The NZ Olympic Health team took a proactive approach to risk mitigation,
      including extensive education, clothing changes, mosquito spray, mosquito nets,
      and voluntary postexposure testing. No positive serology was observed in those
      tested. CONCLUSIONS: The outbreak of Zika virus in Brazil, the associated
      complication of microcephaly, and the evolving understanding of virus
      transmission created significant uncertainty for NZ Olympic team members. The
      proactive approach taken by the health team to the mitigation of risk, combined
      with the anticipated low risk of arbovirus transmission over the period of the
      games, resulted in enhanced confidence from team members and no reports of
      positive serology.

PMID- 29219884
TI  - Abduction in Proximal Hamstring Tendon Avulsion Injury Mechanism-A Report on 3
      Athletes.
AB  - Proximal hamstring tendon avulsions are typically sustained during forced hip
      hyperflexion combined with knee extension. We present 3 cases of athletes with a
      proximal hamstring tendon avulsion caused by an alternative injury mechanism that
      also involves a considerable hip abduction component (flexion-abduction injury
      mechanism). All cases had at least one concurrent injury of the medial thigh
      muscles, either on the ipsilateral or contralateral side. The 2 elite athletes
      with this injury mechanism returned to sport at preinjury level relatively
      quickly. A history of the flexion-abduction mechanism should raise suspicion of a
      hamstring tendon avulsion with concomitant injury of the medial thigh muscles.
      The magnetic resonance imaging (MRI) protocol should include both legs, and any
      concurrent injury may need to be addressed as well. In future studies, it would
      be interesting to investigate whether injury mechanism holds prognostic value in
      proximal hamstring tendon avulsions.

PMID- 29219885
TI  - Displaced Clavicle Fractures in Cyclists: Return to Athletic Activity After
      Anteroinferior Plate Fixation.
AB  - BACKGROUND: One of the most commonly observed injuries in cycling is fracture of
      the clavicle. Nevertheless, there is limited literature available on clinical
      outcomes after plate fixation of clavicle fractures in cyclists, rehabilitation
      protocols, and the time to return to sports. PURPOSE: The aim of this study was
      to evaluate the functional outcome, complications, and return to athletic
      activity at short-term follow-up after surgical repair. STUDY DESIGN: Case
      series. METHODS: Between January 2008 and October 2014, all professional and
      recreational cyclists presenting with a new clavicle fracture at the emergency
      department were prospectively recorded. All patients had an anteroinferior plate
      fixation, variable angle locking compression plate (DePuySynthes). Patients were
      seen at 2, 6, and 24 weeks at the outpatient clinic to gather Disability of the
      Arm, Shoulder, and Hand (DASH) and Constant shoulder questionnaires and
      radiographs were made. Cyclists were allowed to resume outside training 1 week
      after surgery. RESULTS: Ten professional cyclists and 15 recreational cyclists
      were included. All (25/25) patients returned to cycling after plate fixation.
      Mean Constant scores and mean DASH scores of 96.8 +/- 4.1 and 5.1 +/- 5.5 at 6
      weeks and 99.1 +/- 1.5 and 2.9 +/- 4.6 at 24 weeks were measured. There were 3
      complications: 1 patient developed a nonunion, there was 1 wound infection
      requiring antibiotics, and in 1 patient, a refracture occurred. CONCLUSION: Plate
      fixation for cyclists with displaced clavicle fractures was successful in terms
      of fast return to previous level of athletic activity. It is a valuable and safe
      option for athletes in cycling.

PMID- 29219886
TI  - Impact of Clavicle Fractures on Return to Play and Performance Ratings in NFL
      Athletes.
AB  - OBJECTIVE: Clavicle fractures in the National Football League (NFL) have gained
      significant attention because of their impact on high profile athletes; however,
      little has been published on the overall impact of these injuries. This study
      sought to determine the time to return to play and quantitative impact on
      athletic performance after clavicle fractures in NFL athletes. DESIGN:
      Retrospective Cohort Study; Level of evidence, 3. SETTING: Retrospective cohort
      study of NFL athletes based on published injury reports and player statistics.
      PARTICIPANTS: This study consisted of 17 NFL athletes who sustained a clavicle
      fracture from 1998 to 2015 and returned to the field after the injury during the
      study period. Three athletes were excluded from performance analysis because of
      not playing for the entire season after injury. Control groups consisted of
      position-matched NFL athletes who competed in the 2013 NFL season without an
      identified clavicle injury. MAIN OUTCOME MEASURES: Median time to return to play
      after a clavicle fracture and the impact on player performance rating. RESULTS:
      Athletes returned to the competition after a median of 3.47 months after injury
      and missed a median of 8 games. There was no statistically significant impact on
      athletic performance after returning to play. CONCLUSION: Although clavicle
      fractures did have a significant impact on athletes because of lost playing time,
      there was no statistically significant difference in player performance after the
      injury when compared with a control group.

PMID- 29219887
TI  - Short-term Automated Quantification of Radiologic Changes in the Characterization
      of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and
      Prediction of Long-term Survival.
AB  - PURPOSE: Fibrotic interstitial lung diseases presenting with nonspecific and
      overlapping radiologic findings may be difficult to diagnose without surgical
      biopsy. We hypothesized that baseline quantifiable radiologic features and their
      short-term interval change may be predictive of underlying histologic diagnosis
      as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting
      without honeycombing versus nonspecific interstitial pneumonia (NSIP). MATERIALS
      AND METHODS: Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients
      with available high-resolution chest computed tomography 4 to 24 months apart
      were studied. CALIPER software was used for the automated characterization and
      quantification of radiologic findings. RESULTS: IPF subjects were older (66 vs.
      48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher
      volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval
      period, compared with NSIP, IPF patients experienced greater functional decline
      (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as
      noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and
      decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs.
      58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at
      baseline, and greater interval decrease in normal lung volumes were predictive of
      IPF. Both baseline and short-term changes in quantitative radiologic findings
      were predictive of mortality. CONCLUSIONS: Baseline quantitative radiologic
      findings and assessment of short-term disease progression may help characterize
      underlying IPF versus NSIP in those with difficult to differentiate
      clinicoradiologic presentations. Our study supports the possible utility of
      assessing serial quantifiable high-resolution chest computed tomographic findings
      for disease differentiation in these 2 entities.

PMID- 29219888
TI  - Computed Tomography Features associated With the Eighth Edition TNM Stage
      Classification for Thymic Epithelial Tumors.
AB  - PURPOSE: The eighth edition of the TNM classification of malignant tumors for the
      first time includes an official staging system for thymic epithelial tumors
      (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union
      for International Cancer Control (UICC). Staging is critical for the management
      of TETs, and determining stage accurately from imaging has the potential to
      improve clinical outcomes. We examine preoperative computed tomography (CT)
      characteristics of TETs associated with AJCC/UICC pathologic TNM stage. MATERIALS
      AND METHODS: In this retrospective study, patients were included if they met all
      the following criteria: (1) diagnosis of TET, (2) had primary curative intent
      surgery performed at Stanford University, and (3) had available preoperative CT
      imaging for review. Tumor pathology was staged according to the eighth edition
      TNM classification. Fifteen CT scan features were examined from each patient case
      according to the International Thymic Malignancy Interest Group standard report
      terms in a blinded manner. A Lasso-regularized multivariate model was used to
      produce a weighted scoring system predictive of pathologic TNM stage. RESULTS:
      Examining the 54 patients included, the following CT characteristics were
      associated with higher pathologic TNM stage when using the following scoring
      system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score
      of 6), pleural nodule (score of 2), lobulated contour (score of 2), and
      heterogeneous internal density (score of 1). Area under the receiver operating
      characteristic curve was 0.76. CONCLUSIONS: TETs with clearly invasive or
      metastatic features seen on CT are associated with having higher AJCC/UICC
      pathologic TNM stage, as expected. However, features of lobulated contour and
      heterogeneous internal density are also associated with higher stage disease.
      These findings need to be validated in an independent cohort.

PMID- 29219889
TI  - The Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio for
      Detecting Early-onset Neonatal Sepsis.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      neonate early-onset sepsis (EOS) and the neutrophil to lymphocyte ratio (NLR) and
      the platelet to lymphocyte ratio (PLR) of term neonates. MATERIALS AND METHODS:
      This prospective observational study was conducted with term neonates diagnosed
      with EOS compared with 44 healthy controls. Exclusion criteria were prematurity,
      postmaturity, small or large for gestational age according to week of pregnancy,
      preeclampsia, gestational diabetes mellitus, chorioamnionitis, congenital major
      anomalies, and cyanotic congenital heart disease. RESULTS: A total of 122 term
      neonates were included in the study. Of these, 78 were diagnosed with EOS and 44
      were healthy controls. Tachycardia and apnea with bradycardia were the most
      common clinical signs of the onset of EOS in neonates in the EOS group. This
      group had significantly higher neutrophil counts, axillary temperatures, NLRs,
      PLRs, C-reactive proteins, and procalcitonin levels compared with the control
      group. There was a positive association between neutrophil counts, NLR, and PLR
      in the EOS group. An NLR of 6.76 was determined as the predictive cutoff value of
      neonate EOS (sensitivity 97.4%; specificity 100%; area under the receiver
      operating characteristic curve 0.99; P=0.001). A PLR of 94.05 was determined as
      the predictive cutoff value of neonate EOS (sensitivity 97.4; specificity 100%;
      area under the receiver-operating characteristic curve 0.93; P=0.001).
      CONCLUSIONS: NLRs and PLRs were positively correlated with EOS in term neonates,
      and these ratios can be used as diagnostic adjunct tests for neonate EOS workups.

PMID- 29219890
TI  - A Cryptic NUP214-ABL1 Fusion in B-cell Precursor Acute Lymphoblastic Leukemia.
AB  - Fluorescent in situ hybridization (FISH) analysis is the standard methods for
      screening ABL1 fusions, which is recurrently translocated in pediatric acute
      lymphoblastic leukemia (ALL), and potentially targetable by kinase inhibitors.
      Here we demonstrated a case of B-cell precursor ALL with NUP214-ABL1 fusion,
      which break-apart FISH assay for ABL1 failed to detect. The cryptic fusion was
      generated by small duplication from ABL1 to NUP214, which was detected by copy
      number analysis using genomic microarray and confirmed by PCR. In the context of
      precision medicine, we should establish how to screen targetable abnormalities
      for minimizing risk of false-negative.

PMID- 29219891
TI  - Thrombotic Thrombocytopenic Purpura in a Child Treated for Acute Lymphoblastic
      Leukemia: Case Report and Review of Literature.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused
      by deficiency of von Willebrand factor-cleaving protease ADAMTS13. Large von
      Willebrand multimer formation and intravascular platelet aggregation affecting
      the arterioles and capillaries can result in death unless early treatment is
      administered. We report on the case of a child with TTP associated with a human
      herpes virus type-6 infection occurring during chemotherapy for acute
      lymphoblastic leukemia who was effectively treated by fresh frozen plasma
      infusions and antiviral therapy. Although rarely observed in children affected by
      acute lymphoblastic leukemia, TTP is a potentially fatal illness that should be
      considered in the differential diagnosis of thrombocytopenia with hemolytic
      anemia.

PMID- 29219892
TI  - Toxicity of Vincristine Combined With Posaconazole in Children With Acute
      Lymphoblastic Leukemia.
AB  - BACKGROUND: Vincristine (VCR) is one of the main drugs of acute lymphoblastic
      leukemia (ALL) treatment. Azole antifungal medications are used for treatment or
      prophylaxis of invasive fungal infections in acute leukemia. Coadministration of
      these drugs increases the risk of VCR toxicity. OBSERVATIONS: We presented a girl
      with ALL using posaconazole prophylaxis. She developed VCR toxicity that included
      tubulopathy, high blood pressure, neuropathic pain, difficulty walking, diffuse
      muscular weakness, constipation, abdominal pain. CONCLUSIONS: There are limited
      data in children with ALL for posaconazole prophylaxis. We recommend that VCR
      side effects should be evaluated by careful monitoring of the patients who are on
      this combination therapy.

PMID- 29219893
TI  - Editorial.

PMID- 29219894
TI  - Crisis Management Simulation: Establishing a Dual Neurosurgery and Anesthesia
      Training Experience.
AB  - BACKGROUND: Simulation training has been shown to be an effective teaching tool.
      Learner management of an intraoperative crisis such as a major cerebrovascular
      bleed requires effective teamwork, communication, and implementation of key skill
      sets at appropriate time points. This study establishes a first of a kind
      simulation experience in a neurosurgery/anesthesia resident (learners) team
      working together to manage an intraoperative crisis. METHODS: Using a cadaveric
      cavernous carotid injury perfusion model, 7 neurosurgery and 6 anesthesia
      learners, were trained on appropriate vascular injury management using an
      endonasal endoscopic technique. Learners were evaluated on communication skills,
      crisis management algorithms, and implementation of appropriate skill sets at the
      right time. A preanatomic and postanatomic examination and postsimulation survey
      was administered to neurosurgery learners. Anesthesia learners provided
      posttraining evaluation through a tailored realism and teaching survey. RESULTS:
      Neurosurgery learners' anatomic examination score improved from presimulation
      (33.89%) to postsimulation (86.11%). No significant difference between learner
      specialties was observed for situation awareness, decision making, communications
      and teamwork, or leadership evaluations. Learners reported the simulation
      realistic, beneficial, and highly instructive. CONCLUSIONS: Realistic, first of
      kind, clinical simulation scenarios were presented to a neurosurgery/anesthesia
      resident team who worked together to manage an intraoperative crisis. Learners
      were effectively trained on crisis management, the importance of communication,
      and how to develop algorithms for future implementation in difficult scenarios.
      Learners were highly satisfied with the simulation training experience and
      requested that it be integrated more consistently into their residency training
      programs.

PMID- 29219895
TI  - Effect Of 8-Week of Hospital-Based Resistance Training Program on TCD4+ Cell
      Count and Anthropometric Characteristic of HIV Patients in Tehran, Iran: A
      Randomized Controlled Trial.
AB  - We examined the effects of an 8 w circuit resistance training (RES) program using
      elastic bands and body weight on TCD4+ cell counts and anthropometry in HIV
      patients. Patients (N=21) receiving antiretroviral therapy were randomly assigned
      to resistance training (RES; n=14) or control group (CON; n=7) groups. RES (3/w)
      consisted of training with elastic bands and bodyweight training focusing on
      major muscle groups. CON received standard care. Statistical analyses were
      performed using general linear models adjusted for age, gender, length of
      infection and respective baseline measures. The primary outcome was TDC4+ and
      secondary outcomes were anthropometry indices. Tertiary assessments explored
      Pearson correlations surrounding the relationship between changes in
      anthropometry and TDC4+. We observed significant increases in TCD4+ count
      accompanying RES training (105.50 cells/mm3, 95% CI, 47.42, 163.59), while CON
      significantly decreased (-41.01 cells/mm3, 95% CI, -126.78, 44.76). Significant
      between group differences were noted (P<0.02; n=0.42). We also observed
      significant reductions in fat mass for RES (1.18 kg, 95% CI, =1.80, -0.56) vs.
      increased fat mass for CON (1.21 kg, 95% CI, 0.31, 2.11). Significant between
      group differences were noted (P=0.001, n=0.64). Similar effects were noted for
      lean body mass. No significant changes were observed for body weight. Significant
      correlations were observed for fat mass (r = -0.699, P=0.001) and lean mass (r =
      0.553, P=0.017), but not body weight (r =-0.390, P=0.109) vs. changes in TDC4+.
      Our results suggest the RES program used in this study is effective for improving
      TDC4+ status and body composition in HIV patients.

PMID- 29219896
TI  - Analysis of Training Loads in Elite Under 18 Australian Rule Football Players.
AB  - Cust, EE, Elsworthy, N, and Robertson, S. Analysis of training loads in elite
      under 18 Australian rule football players. J Strength Cond Res 32(9): 2521-2528,
      2017-Differences in training loads (TLs) between under 18 (U18) Australian rules
      football (AF) state academy-selected and state academy-nonselected players were
      investigated. Players were categorized relating to their highest representative
      level: state academy-selected (n = 9) and TAC cup-level players (n = 38). Data
      were obtained from an online training-monitoring tool implemented to collect
      player training and match information across a 20-week period during the regular
      season. Parameters modeled included AF skills, strength, and other sport training
      sessions. Descriptive statistics (mean +/- SD) and between-group comparisons
      (Cohen's d) were computed. A J48 decision tree modeled which TL variables could
      predict selection level. Pooled data showed 60% of weekly training duration
      consisted of AF training sessions. Similar AF TL were reported between state
      academy and TAC cup players (1,578 +/- 1,264 arbitrary units (AU) vs. 1,368 +/-
      872 AU; d = 0.05). Although higher TLs were reported for state-selected players
      comparative with TAC cup in total training (d = 0.20), core stability (d = 0.36),
      flexibility (d = 0.44), on-feet conditioning (d = 0.26), and off-feet
      conditioning (d = 0.26). Decision tree analysis showed core stability duration
      and flexibility TL, the most influential parameters in classifying group
      selection (97.7% accuracy TAC cup level; 35.8% accuracy state academy level).
      Insights of U18 AF players' weekly training structures, loads, and
      characteristics of higher achieving players are provided. This study supports the
      application of training diaries and session rating of perceived exertion for TL
      monitoring in junior athletes.

PMID- 29219897
TI  - Management of Complex Epithelial Ingrowth After Laser In Situ Keratomileusis
      Using Fibrin Tissue Glue.
AB  - OBJECTIVES: To evaluate the efficacy and safety of adjunctive fibrin tissue glue
      in the treatment of complex epithelial ingrowth after laser in situ
      keratomileusis (LASIK). METHODS: A retrospective review was performed of 12 eyes
      in 12 patients treated for clinically significant epithelial ingrowth after LASIK
      with mechanical debridement of the ingrowth and placement of fibrin tissue glue.
      Primary outcome measurements including recurrence of ingrowth, visual acuity, and
      manifest refraction were evaluated at each postoperative examination. Changes in
      higher-order aberrometry were also evaluated. RESULTS: After epithelial ingrowth
      removal with adjunctive fibrin tissue glue, 11 eyes (91.7%) had no recurrence of
      ingrowth at the final follow-up examination. Uncorrected distance visual acuity
      changed from 20/20 or better in 3 eyes (25%) and 20/40 or better in 6 eyes (50%)
      preoperatively to 20/20 or better in 5 eyes (41.7%) and 20/40 or better in 10
      eyes (83.3%) postoperatively. Nine eyes (75%) gained one or more lines of best
      corrected distance visual acuity (CDVA). No eyes lost any lines of CDVA. There
      was no significant change in mean spherical equivalent (P=0.22) or mean cylinder
      (P=0.26) before and after surgery. Higher-order aberrations also remained stable
      with no significant change in root-mean-square error, coma, trefoil, and
      spherical aberration. There were no complications associated with the treatment.
      CONCLUSIONS: Adjunctive fibrin tissue glue seems to be a safe and effective
      treatment for epithelial ingrowth after LASIK. This therapy may be particularly
      useful in managing challenging cases of complex or recalcitrant ingrowth.

PMID- 29219898
TI  - Orthokeratology and Contact Lens Quality of Life Questionnaire (OCL-QoL).
AB  - OBJECTIVES: To develop a quality of life (QoL) instrument for patients fitted
      with Orthokeratology (OrthoK) and other modalities of contact lenses. METHODS: A
      45-item pilot questionnaire was developed from an extensive literature review,
      focus groups, and interviews. Subsequently, 234 participants fitted with contact
      lenses (OrthoK, soft lenses, and gas permeable lenses) or spectacles completed
      the pilot questionnaire. Rasch analysis was used to assess the psychometric
      properties in terms of person separation, item fit statistics, category threshold
      ordering, differential item functioning (DIF), and targeting. A subset of
      participants completed the final questionnaire twice (1 week apart) and the
      repeatability assessed (within-subject standard deviation). The Spearman rank
      order correlation coefficient between the questionnaire score and binocular
      visual acuity was calculated to assess construct validity. RESULTS: Inspection of
      category probability curves suggested that one category was underused and the
      response options were collapsed. Furthermore, Rasch analyses indicated 22 items
      misfitted the model and were removed. The final questionnaire contained 23 items
      with a person separation of 2.18, item fit statistics within the range 0.83 to
      1.15, targeting 1.05 logits, and no significant DIF (<0.8 logits). The
      repeatability (Sr) was 4.21 and there was no correlation between questionnaire
      scores and binocular visual acuity (rs=0.03, P=0.65). CONCLUSIONS: The
      Orthokeratology and Contact Lens Quality of Life Questionnaire demonstrated
      excellent psychometric properties and is capable of measuring vision-related QoL
      in patients fitted with various forms of contact lenses including OrthoK lenses.
      The tool is scored on a 0 to 100 interval level scale with higher scores
      indicating better QoL.

PMID- 29219899
TI  - Clinical Outcomes Using Oversized Back Plates in Type I Boston Keratoprosthesis.
AB  - OBJECTIVES: To examine clinical outcomes of oversized titanium back plates in
      type I Boston keratoprosthesis (KPro) implantation. METHODS: Retrospective study
      of 22 sequential eyes (20 patients) undergoing type I KPro implantation with an
      oversized titanium back plate (larger than trephined wound diameter by 1.0 mm or
      more), performed by a single surgeon (K.A.C.) from June 2010 to November 2014.
      Data were collected regarding preoperative eye characteristics, surgical details,
      and postoperative clinical outcomes. RESULTS: Mean follow-up time per eye was
      24.1+/-14.9 months. All eyes had improved vision after surgery; 13 eyes (59.1%)
      maintained visual acuity improvement at last follow-up. Initial KPro's were
      retained in 19 eyes (86.4%); one eye required KPro replacement. Primary
      retroprosthetic membrane (RPM) developed in three eyes (13.6%), with similar
      occurrence in aniridic (14.3%) and nonaniridic eyes (13.3%). Secondary RPM's
      developed in two eyes (9.1%) after vitritis (one eye) and retinal and choroidal
      detachment (one eye). Glaucoma was a common comorbidity: 2 of 14 eyes (14.3%)
      with preoperative glaucoma had glaucoma progression, and 4 of 8 eyes (50.0%)
      without preoperative glaucoma developed glaucoma postoperatively. Other
      postoperative complications included retinal detachment (5 eyes, 22.7%) and
      idiopathic vitritis (3 eyes, 13.6%). CONCLUSIONS: Oversized titanium KPro back
      plates are associated with a low rate of primary RPM formation and may have
      particular utility in reducing primary RPM formation in aniridic eyes. Glaucoma
      remains a challenge in postoperative KPro management. Complex eyes, at increased
      risk of postoperative complications, require careful management.

PMID- 29219900
TI  - Diagnostic Challenges in Nocardia Keratitis.
AB  - OBJECTIVE: To present a case of diagnostic confusion in Nocardia keratitis in a
      contact lens wearer and to illustrate the characteristic clinical findings of
      this rare entity. METHODS: Case report of Nocardia keratitis that was mistaken
      for acanthamoeba, herpetic, and fungal keratitis in three tertiary corneal
      referral centers before the correct diagnosis of Nocardia infection was made.
      RESULTS: A 29-year-old contact lens wearer was referred to our hospital for a
      contact lens-associated bacterial keratitis, not improving under standard
      bacterial treatment. Biomicroscopy revealed a circular corneal ulcer and pinhead
      lesions arranged in a wreath pattern. Initial scraping revealed no positive
      cultures and confocal microscopy findings were suspicious for fungal keratitis.
      Only after a poor response to protozoal and fungal treatment, and a negative
      herpes serology, Nocardia was suspected. This suspicion was confirmed with a
      positive culture and the topical amikacin and ciprofloxacin were started. The
      infiltrate responded promptly and resolved, leaving a small corneal scar and a
      good visual recovery. CONCLUSION: Because of its infrequent occurrence and its
      variable clinical picture, Nocardia keratitis is easily misdiagnosed. Although a
      rare entity, this infection should be added to the differential diagnosis in
      contact lens-related keratitis not responding to first-line antibiotics and
      presenting with patchy anterior stromal infiltrates.

PMID- 29219901
TI  - Shifting the Paradigm: Educating Nurse Administrators to be Full Partners.
AB  - In this month's CGEAN column, leaders discuss the current complexities of
      healthcare requiring nurses to practice competently in interprofessional
      partnerships. Nurse administrators and executives play a key role in leading
      culture change so the benefits of full partnership are realized.

PMID- 29219902
TI  - Disseminating Knowledge Through Publication: Magnet(r) Nurses Changing Practice.
AB  - Clinical nurses and nurse leaders are inspiring and fostering amazing outcomes.
      In this column, the new Magnet Recognition Program(r) director discusses the
      expectation for dissemination of outcomes from Magnet(r)-designated organizations
      building on work presented at the 2017 National Magnet ConferenceTM.

PMID- 29219903
TI  - Nursing Staff Perceptions of Fall Risk: The Emergence of Learned Helplessness as
      a Theme.
AB  - Nurses and unlicensed assistive personnel on 2 medical-surgical units were asked
      about their perceptions regarding patient falls. Their responses reflect learned
      helplessness and a lack of nurse empowerment that are relevant findings as nurse
      executives work to decrease patient falls.

PMID- 29219904
TI  - Incivility in the Emergency Department: Implications for Nurse Leaders.
AB  - Uncivil behavior leads to low self-esteem, anxiety, sleep disturbance, recurrent
      nightmares, and depression. This article looks at the perception of incivility
      among emergency department nurses and the leadership required to implement
      evidence-based strategies to address this growing problem.

PMID- 29219905
TI  - Systems Addressing Frail Elder Care: Description of a Successful Model.
AB  - OBJECTIVE: The aim of this article is to describe the Systems Addressing Frail
      Elder (SAFE) Care model, features of the interprofessional team and reengineered
      workflow, and details of the intervention. BACKGROUND: Older inpatients are
      vulnerable to adverse events related to frailty. SAFE Care, an interprofessional
      team-based program, was developed and evaluated in a cluster randomized
      controlled trial (C-RCT). Results found reduced length of stay and complications.
      The purpose of this article is to support and encourage the replication of this
      innovation or to help facilitate implementation of a similar process of
      organizational change. METHODS: This was a review of model features and
      intervention data abstracted from electronic health records. RESULTS: Salient
      features of team composition, training, and workflow are presented. The C-RCT
      intention-to-treat sample included 792 patients, of whom 307 received the SAFE
      Care huddle intervention. The most frequent problem was mobility (85.7%), and
      most frequent recommendation was fall precautions protocol (83.1%). CONCLUSIONS:
      The SAFE Care model may provide a standardized framework to approach, assess, and
      address the risks of hospitalized older adults.

PMID- 29219906
TI  - Targeted Interventions to Advance a Culture of Inquiry at a Large, Multicampus
      Hospital Among Nurses.
AB  - OBJECTIVES: The aim of this study is to assist nurse leaders in developing
      innovative structures to foster a culture of inquiry among professional nurses.
      BACKGROUND: Critical to nurse's engagement in evidence-based practice (EBP) is a
      culture of inquiry, in which nurses critically evaluate patient care activities
      and actively review existing evidence to address identified clinical issues. A
      bundle of structural interventions was implemented across a large, multisite
      hospital to advance a culture of inquiry. We measured the impact of these
      interventions on nurses' library use and on nurses' knowledge, attitudes, and
      practices towards EBP. METHODS: Structural interventions included: 1) EBP and
      Research Committee meetings, in which nurses were educated on how to formulate a
      clinical question and critically appraise a research article; 2) Academic
      Partners Program, in which nurse academicians provided scholarly mentorship and
      guidance during monthly committee meetings; 3) hiring of clinical nurse
      scientists who provided 1-on-1 education and mentorship to clinical nurses in EBP
      and research; and 4) a Nurse Residency Program partnership, in which newly
      graduated nurses were required to complete an EBP project. We examined the impact
      of these structural interventions on nurses' use of library resources and nurses'
      knowledge, attitudes, and practices toward EBP. RESULTS: The implementation of
      structural interventions to support nurses' engagement in EBP was associated with
      a significant increase in the number of nurse-generated library consultative
      requests over time. Results showed high levels of nurse knowledge, attitudes, and
      practices in EBP. CONCLUSIONS: Nurse leaders may advance a culture of inquiry by
      providing the infrastructure to support EBP activities and by empowering nurses
      to question and seek answer to identified practice questions. Infrastructures
      should include access to scientific articles and partnerships with schools of
      nursing. Additional research is needed to validate nurse library use as a measure
      of nurse engagement in EBP.

PMID- 29219907
TI  - The Implementation of a Structured Nursing Leadership Development Program for
      Succession Planning in a Health System.
AB  - Preparing future nursing leaders to be successful is important because many
      current leaders will retire in large numbers in the future. A structured nursing
      leadership development program utilizing the Essentials of Nurse Manager
      Orientation online program provided future nursing leaders with content aligned
      with nursing leadership competencies. Paired with assigned mentors and monthly
      leadership sessions, the participants increased their perception of leadership
      competence.

PMID- 29219908
TI  - Characteristics of the Nursing Practice Environment Associated With Lower Unit
      Level RN Turnover.
AB  - OBJECTIVE: The aim of this study is to examine characteristics of the nursing
      practice environment associated with lower RN turnover. BACKGROUND: Identifying
      characteristics of the practice environment that contribute to lower RN turnover
      is important for meeting the national quality strategy priority of reducing
      healthcare costs. METHODS: Data from 1002 adult care units in 162 National
      Database of Nursing Quality Indicators participating hospitals were analyzed
      using multivariate linear regression. The Practice Environment Scale of the
      Nursing Work Index was used to measure practice environment characteristics. RN
      turnover was measured at the unit level. RESULTS: Nursing units with higher
      overall ratings of the nursing practice environment had lower rates of RN
      turnover. Units with higher RN perceived staffing and resource adequacy
      experienced significantly lower RN turnover. CONCLUSIONS: Unit managers and
      hospital administrators should consider RN perception of staffing and resource
      adequacy and the overall practice environment when developing targeted strategies
      for decreasing RN turnover.

PMID- 29219909
TI  - A Thematic Analysis of Self-described Authentic Leadership Behaviors Among
      Experienced Nurse Executives.
AB  - OBJECTIVE: The aim of this study is to understand the behaviors experienced nurse
      executives use to create healthy work environments (HWEs). The constructs of
      authentic leadership formed the conceptual framework for the study. BACKGROUND:
      The American Association of Critical-Care Nurses recommends authentic leadership
      as the preferred style of leadership for creating and sustaining HWEs. Behaviors
      associated with authentic leadership in nursing are not well understood. METHODS:
      A purposive sample of 17 experienced nurse executives were recruited from across
      the United States for this qualitative study. Thematic analysis was used to
      analyze the in-depth, semistructured interviews. RESULTS: Four constructs of
      authentic leaders were supported and suggest unique applications of each
      including self-awareness (a private and professional self), balanced processing
      (open hearted), transparency (limiting exposure), and moral leadership (nursing
      compass). CONCLUSIONS: Authentic leadership may provide a sound foundation to
      support nursing leadership practices; however, its application to the discipline
      requires additional investigation.

PMID- 29219910
TI  - The Appraisal of Nursing Practice: Instrument Development and Initial Testing.
AB  - OBJECTIVE: We describe the development of the Appraisal of Nursing Practice (ANP)
      and present initial psychometric data. BACKGROUND: Although measures of new
      nurses' confidence in clinical practice exist, psychometrically sound
      observational tools that assess a broad range of nursing competencies are needed.
      METHODS: Based on the Quality and Safety Education for Nurses competencies, the
      37-item ANP covers person-centered care, teamwork and collaboration, evidence
      based practice/quality improvement, safety, informatics, professionalism, and
      overall satisfaction (with the new nurse's functioning). Cognitive interviewing
      was used to refine the items. Assessment of interrater reliability and a field
      test in a new nurse residency program were conducted. RESULTS: Interrater
      reliability and internal consistency reliability were generally acceptable.
      Scores increased significantly for nurses as they moved through a nurse residency
      program. CONCLUSIONS: The ANP can help nursing administrators identify areas
      where nurse residents are building needed competencies versus areas that need
      more work to achieve desired competency outcomes.

PMID- 29219911
TI  - Practical Application of High-Reliability Principles in Healthcare to Optimize
      Quality and Safety Outcomes.
AB  - Application of high-reliability (HR) principles into daily healthcare processes
      can drive culture change, safety, and quality outcomes. Understanding
      foundational practices to full HR principle integration in an organization's
      quality and safety programs strengthens evidence-based practices, reduces
      clinical variation, and improves nurse-sensitive patient outcomes. Quantifying
      the cost impact of reduction in preventable harm and improved nurse-sensitive
      patient outcomes is an initial attempt to formulate an empiric measure of nursing
      value.

PMID- 29219912
TI  - Progress.

PMID- 29219913
TI  - With Colorectal Cancer Treatment, Physical Toxicity Is Not the Only Concern.

PMID- 29219914
TI  - The Hawthorne Effect Revisited.

PMID- 29219915
TI  - Not Taking "No" for an Answer.

PMID- 29219916
TI  - The American Society of Colon and Rectal Surgeons Clinical Practice Guideline for
      the Prevention of Venous Thromboembolic Disease in Colorectal Surgery.

PMID- 29219917
TI  - Evaluation and Management of Rectovaginal Fistulas.

PMID- 29219918
TI  - Expert Commentary on the Evaluation and Management of Rectovaginal Fistulas.

PMID- 29219919
TI  - Financial Impact of Colorectal Cancer and Its Consequences: Associations Between
      Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.
AB  - BACKGROUND: The financial impact and consequences of cancer on the lives of
      survivors remain poorly understood. This is especially true for colorectal
      cancer. OBJECTIVE: We investigated objective cancer-related financial stress,
      subjective cancer-related financial strain, and their association with health
      related quality of life in colorectal cancer survivors. DESIGN: This was a cross
      sectional postal survey. SETTINGS: The study was conducted in Ireland, which has
      a mixed public-private healthcare system. PATIENTS: Colorectal cancer survivors,
      diagnosed 6 to 37 months prior, were identified from the population-based
      National Cancer Registry. MAIN OUTCOME MEASURES: Cancer-related financial stress
      was assessed as impact of cancer on household ability to make ends meet and
      cancer-related financial strain by feelings about household financial situation
      since cancer diagnosis. Health-related quality of life was based on European
      Organisation for Research and Treatment of Cancer QLQ-C30 global health status.
      Logistic regression was used to identify associations between financial stress
      and strain and low health-related quality of life (lowest quartile, score <=50).
      RESULTS: A total of 493 survivors participated. Overall, 41% reported cancer
      related financial stress and 39% cancer-related financial strain; 32% reported
      both financial stress and financial strain. After adjustment for sociodemographic
      and clinical variables, the odds of low health-related quality of life were
      significantly higher in those who reported cancer-related financial stress
      postdiagnosis compared with those who reported no change in financial stress
      postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related
      quality of life were also significantly higher in those with worse financial
      strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both
      cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59
      4.22). LIMITATIONS: Survey responders were younger, on average, than
      nonresponders. Responders and nonresponders may have differed in cancer-related
      financial stress and strain or health-related quality of life. CONCLUSIONS: Four
      in 10 colorectal cancer survivors reported an adverse financial impact of cancer.
      Cancer-related financial stress and strain were significantly associated with low
      health-related quality of life. To inform support strategies, additional research
      is needed to better understand how both objective and subjective financial
      distress influence survivors' health-related quality of life. See Video Abstract
      http://links.lww.com/DCR/A447.

PMID- 29219920
TI  - The Fatty Liver Index: A Simple and Accurate Predictor of Colorectal Adenoma in
      an Average-Risk Population.
AB  - BACKGROUND: Nonalcoholic fatty liver disease, the hepatic manifestation of
      metabolic syndrome, is associated with increased risk of colorectal adenoma, a
      precursor of colorectal cancer. Because nonalcoholic fatty liver disease and
      colorectal adenoma share many common risk factors of metabolic syndrome, the
      association between these 2 pathological findings has been investigated in
      multiple studies, but the results have been conflicting. OBJECTIVE: The present
      study aimed to assess the relationship between the fatty liver index, a predictor
      of nonalcoholic fatty liver disease, and the prevalence of colorectal adenomas.
      DESIGN: This is a retrospective observational study. SETTINGS: This study was
      conducted at a single expert center. PATIENTS: A total of 2976 consecutive
      subjects over 40 years of age undergoing routine checkups including abdominal
      ultrasonography and colonoscopy at Chung-Ang University Hospital Health Care
      Center were included. MAIN OUTCOME MEASURES: The primary outcome measured was the
      prevalence of colorectal adenomas according to fatty liver index. RESULTS: Among
      these subjects, 932 (31.3%) had colorectal adenoma, 691 (23.2%) had metabolic
      syndrome, and 1512 (50.8%) had fatty liver on ultrasonography. In multivariate
      analysis, fatty liver index >=30 was associated with an increased risk of
      colorectal adenoma (OR, 1.269; 95% CI, 1.06-1.49; p = 0.008). The fatty liver
      index-high group (fatty liver index >=30) had more colorectal adenomas and more
      advanced colorectal adenomas than the fatty liver index-low group (fatty liver
      index <30) (p < 0.001 and p = 0.042). The prevalence of colorectal adenomas
      increased with increasing quartile of fatty liver index (p < 0.05). LIMITATIONS:
      The study was limited by a relatively healthy Asian population. CONCLUSION: The
      high fatty liver index may be a useful predictor of colorectal adenoma. See Video
      Abstract at http://links.lww.com/DCR/A478.

PMID- 29219921
TI  - Colorectal Cancer Safety Net: Is It Catching Patients Appropriately?
AB  - BACKGROUND: Disparities in access to colorectal cancer care are multifactorial
      and are affected by socioeconomic elements. Uninsured and Medicaid patients
      present with advanced stage disease and have worse outcomes compared with similar
      privately insured patients. Safety net hospitals are a major care provider to
      this vulnerable population. Few studies have evaluated outcomes for safety net
      hospitals compared with private institutions in colorectal cancer. OBJECTIVE: The
      purpose of this study was to compare demographics, screening rates, presentation
      stage, and survival rates between a safety net hospital and a tertiary care
      center. DESIGN: Comparative review of patients at 2 institutions in the same
      metropolitan area were conducted. SETTINGS: The study included colorectal cancer
      care delivered either at 1 safety net hospital or 1 private tertiary care center
      in the same city from 2010 to 2016. PATIENTS: A total of 350 patients with
      colorectal cancer from each hospital were evaluated. MAIN OUTCOME MEASURES:
      Overall survival across hospital systems was measured. RESULTS: The safety net
      hospital had significantly more uninsured and Medicaid patients (46% vs 13%; p <
      0.001) and a significantly lower median household income than the tertiary care
      center ($39,299 vs $49,741; p < 0.0001). At initial presentation, a similar
      percentage of patients at each hospital presented with stage IV disease (26% vs
      20%; p = 0.06). For those undergoing resection, final pathologic stage
      distribution was similar across groups (p = 0.10). After a comparable median
      follow-up period (26.6 mo for safety net hospital vs 29.2 mo for tertiary care
      center), log-rank test for overall survival favored the safety net hospital (p =
      0.05); disease-free survival was similar between hospitals (p = 0.40).
      LIMITATIONS: This was a retrospective review, reporting from medical charts.
      CONCLUSIONS: Our results support the value of safety net hospitals for providing
      quality colorectal cancer care, with survival and recurrence outcomes equivalent
      or improved compared with a local tertiary care center. Because safety net
      hospitals can provide equivalent outcomes despite socioeconomic inequalities and
      financial constraints, emphasis should be focused on ensuring that adequate
      funding for these institutions continues. See Video Abstract at
      http://links.lww.com/DCR/A454.

PMID- 29219922
TI  - Multimodal Prehabilitation Programs as a Bundle of Care in Gastrointestinal
      Cancer Surgery: A Systematic Review.
AB  - BACKGROUND: Prehabilitation reflects a proactive process of preoperative
      optimization undertaken between cancer diagnosis and definitive surgical
      treatment, with the intent of improving physiological capacity to withstand the
      major insult of surgery. Prehabilitation before GI cancer surgery is currently
      not widely adopted, and most research has focused on unimodal interventions such
      as exercise therapy, nutritional supplementation, and hematinic optimization. A
      review of the existing literature was undertaken to investigate the impact of
      multimodal prehabilitation programs as a "bundle of care." DATA SOURCE: A
      systematic literature search was performed utilizing Medline, PubMed, Embase,
      Cinahl, Cochrane, and Google Scholar databases. STUDY SELECTION: The quality of
      studies was assessed by using the Cochrane tool for assessing risk of bias
      (randomized trials) and the Newcastle-Ottawa Quality Assessment scale (cohort
      studies). INTERVENTION: Studies were chosen that involved pre-operative
      optimization of patients before GI cancer surgery. MAIN OUTCOMES: The primary
      outcome measured was the impact of prehabilitation programs on preoperative
      fitness and postoperative outcomes. RESULTS: Of the 544 studies identified, 20
      were included in the qualitative analysis. Two trials investigated the impact of
      multimodal prehabilitation (exercise, nutritional supplementation, anxiety
      management). Trials exploring prehabilitation with unimodal interventions
      included impact of exercise therapy (7 trials), impact of preoperative iron
      replacement (5 trials), nutritional optimization (5 trials), and impact of
      preoperative smoking cessation (2 trials). Compliance within the identified
      studies was variable (range: 16%-100%). LIMITATIONS: There is a lack of
      adequately powered trials that utilize objective risk stratification and uniform
      end points. As such, a meta-analysis was not performed because of the
      heterogeneity in study design. CONCLUSION: Although small studies are supportive
      of multimodal interventions, there are insufficient data to make a conclusion
      about the integration of prehabilitation in GI cancer surgery as a bundle of
      care. Larger, prospective trials, utilizing uniform objective risk stratification
      and structured interventions, with predefined clinical and health economic end
      points, are required before definitive value can be assigned to prehabilitation
      programs.

PMID- 29219923
TI  - Multimodal Use of Fluorescent Imaging in Colorectal Cancer Surgery.

PMID- 29219924
TI  - Combined Laparoscopic and Perineal Approach to Omental Interposition Repair of
      Complex Rectovaginal Fistula.
AB  - INTRODUCTION: Surgical repair of rectovaginal fistula remains a challenge.
      Complex and recurrent rectovaginal fistula repairs often fail because of scarring
      and devascularization of the surrounding tissue. Omental interposition may
      promote healing by introducing bulky vascularized tissue into the rectovaginal
      septum. TECHNIQUE: With the patient in the lithotomy position, the rectovaginal
      septum was dissected transperineally up to the fistula tract and the openings on
      both vaginal and rectal sides were closed using interrupted, absorbable sutures.
      The dissection was continued cranially to meet the laparoscopic dissection from
      above. The laparoscopic surgeon detached the omentum from the colon, then the
      anastomotic arterial branches between the Barlow's arcade and the gastroepiploic
      arcade were divided and the greater omentum was mobilized, retaining blood supply
      from the left gastroepiploic artery. The rectum was then mobilized commencing on
      the right lateral side of the mesorectum and then proceeding anteriorly. The
      peritoneum between the rectum and the vagina was incised and the anterior
      mobilization was continued to connect with the perineal dissection. The mobilized
      omentum was pulled down between the rectum and the vagina.The perineal operator
      secured the omentum around the rectal closure and at skin level with absorbable
      sutures. All of the patients had a defunctioning ileostomy or colostomy before
      omental repair. RESULTS: Patients underwent repair for complex or recurrent
      rectovaginal fistulas with this novel approach. Fistula healing was evaluated
      during examination under anaesthesia. All of the patients had completely healed
      at the latest follow-up (median = 15 mo; range, 8-41 mo). Postoperative
      complications included 1 superficial wound infection that was treated
      conservatively and 1 rectovaginal hematoma, which required CT-guided aspiration.
      CONCLUSIONS: Combined laparoscopic omental interposition with perineal
      rectovaginal fistula repair is a safe and effective treatment for complex
      rectovaginal fistulas.

PMID- 29219925
TI  - Which Trial to Demonstrate the Truthfulness of a Tailored Strategy in Rectal
      Carcinoma?

PMID- 29219926
TI  - The Miracle Machine.

PMID- 29219927
TI  - The Authors Reply.

PMID- 29219928
TI  - Should Considerations in Patient Dignity Affect Our Surgical Decisions?

PMID- 29219931
TI  - BILATERAL UVEAL METASTASES SECONDARY TO PROSTATE ADENOCARCINOMA.
AB  - PURPOSE: To report a patient with bilateral uveal metastases secondary to
      previously quiescent prostate adenocarcinoma with a 22-month follow-up. METHODS:
      Retrospective chart review was performed for this patient. RESULTS: Androgen
      deprivation therapy and external beam radiation therapy were shown to manage
      ocular symptoms in a sixty-nine-year-old man previously diagnosed with
      adenocarcinoma of the prostate. CONCLUSION: Uveal metastases can be the first
      site of systemic metastasis even long after initial diagnosis and treatment of
      prostate adenocarcinoma; the 17 years between this patient's treatment for
      adenocarcinoma and commencement of his ocular symptoms is the longest interval
      reported. Hormonal therapy, in conjunction with radiation therapy, can
      successfully reduce tumor burden in these patients and improve visual symptoms
      over time.

PMID- 29219932
TI  - CUTICULAR DRUSEN IN AN INDIGENOUS AUSTRALIAN.
AB  - BACKGROUND/PURPOSE: To report a case of cuticular drusen in an indigenous
      Australian. METHODS: A 37-year-old indigenous (aboriginal) Australian woman from
      a remote Western Australian town presented with a 2-month history of vision loss.
      Clinical history, examination, and multimodal retinal imaging data from spectral
      domain optical coherence tomography, fundus autofluorescence, fluorescein
      angiography, and indocyanine green angiography were analyzed. RESULTS: Multimodal
      imaging confirmed cuticular drusen complicated by a right choroidal
      neovascularization with pigment epithelial detachment and a left foveal
      vitelliform lesion. An unusual "negative-staining" pattern was noted on late
      phase indocyanine green angiography and this spared the regions affected by
      cuticular drusen. CONCLUSION: To the best of our knowledge, this is the first
      published report of cuticular drusen in an indigenous Australian. We hypothesize
      that this may be secondary to ancestral mixing of the gene pool. An unusual
      staining pattern witnessed on indocyanine green angiography suggests widespread
      disturbance of lipoprotein deposition in the Bruch membrane.

PMID- 29219933
TI  - Death, coronary revascularization choices, and chronic kidney disease.

PMID- 29219934
TI  - Visualizing the vascular effects of smoking.

PMID- 29219935
TI  - Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an
      Enhanced Recovery Protocol: A Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Management of postoperative pain after laparoscopic
      segmental colonic resections remains controversial. We compared 2 methods of
      analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of
      the study was to investigate whether administration of intrathecal
      bupivacaine/morphine would lead to an enhanced recovery. METHODS: A single
      center, randomized, double-blind controlled trial was performed (NL43488.101.13).
      Patients scheduled for laparoscopic segmental intestinal resections were
      considered. Exclusion criteria were patients in whom contraindications to spinal
      anesthesia were present, conversion to open surgery, and gastric and rectal
      surgery. The intervention group received single-shot intrathecal
      bupivacaine/morphine (12.5 mg/300 MUg), with an altered dose for older patients.
      The control group received a sham procedure and a bolus of piritramide (0.1
      mg/kg). Both groups received standardized general anesthesia and a patient
      controlled intravenous analgesia pump as postoperative analgesia. All patients
      were treated according to an ERAS protocol. A decrease in days to "fit for
      discharge" was the primary outcome. RESULTS: Fifty-six patients were enrolled.
      Intervention group patients were fit for discharge earlier (median of 3 vs 4
      days, P = 0.044). Furthermore, there was a significant decrease in opioid use and
      lower pain scores on the first postoperative day in the intervention group. There
      were no differences in adverse events (except for more pruritus), time to
      mobilization, fluid administration, or patient satisfaction. CONCLUSIONS: This
      randomized controlled trial shows that intrathecal morphine is a more effective
      method of postoperative analgesia in laparoscopic surgery than intravenous
      opioids within an ERAS program. Recovery is faster and less painful with
      intrathecal morphine. Other studies have confirmed these results, although data
      on faster recovery are new and require confirmation in future trials. CLINICAL
      TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
      NCT02284282.

PMID- 29219936
TI  - End-of-Life Care Discussion for Residents With Dementia in Long-Term Care
      Facilities.
AB  - BACKGROUND: Healthcare professionals play an important role in end-of-life care
      decisions. Although the factors affecting end-of-life care in long-term care
      facilities have been well studied in Western contexts, few studies have examined
      factors affecting end-of-life care discussions for residents with dementia among
      multidisciplinary professionals in Asian or Taiwanese contexts. PURPOSE: The aim
      of this study was to explore the factors related to the end-of-life care
      discussions of registered nurses, social workers, and physicians with residents
      with dementia and their families. METHODS: This is a cross-sectional and
      correlational study. A stratified random sampling was conducted, and self
      administered questionnaires were mailed to physicians, registered nurses, and
      social workers who work in long-term care facilities with accreditation ranks >=
      Grade A in Taiwan. RESULTS: Questionnaires were returned by 478 participants
      (response rate = 94.1%). Fewer than 10% of the participants reported often
      discussing end-of-life care with residents with dementia and their families.
      Physicians were significantly more likely to discuss life-sustaining treatment
      than nurses and social workers. The frequency of professionals discussing advance
      directives and life-sustaining treatment for residents with dementia was
      predicted by higher confidence in end-of-life care skills and greater perceived
      facility support. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Most professionals did
      not frequently discuss end-of-life care with residents with dementia and their
      caregivers. Discussions of end-of-life care in long-term care facilities should
      be promoted by enhancing the confidence of these professionals in providing end
      of-life care and creating a supportive environment for end-of-life discussions
      and care.

PMID- 29219937
TI  - Relationship Between Maternal Characteristics and Postpartum Hemorrhage: A Meta
      Analysis Study.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal death in
      low-income countries and the primary cause of approximately one of every four
      maternal deaths worldwide. PURPOSE: The aim of this study was to determine the
      antenatal risk factors of PPH and its effects. METHODS: The literature from nine
      databases was reviewed, and studies published between 2000 and 2012 were analyzed
      using terms such as "postpartum hemorrhage," "prevention of postpartum
      hemorrhage," and "management of postpartum hemorrhage." The full text of 1,061
      articles was reviewed, and 29 studies were selected according to the inclusion
      criteria. Studies that determined bias using the funnel plot test were excluded,
      and 20 studies were included in the meta-analysis. The data were analyzed using
      Microsoft Office Excel 2010 and comprehensive meta-analysis. RESULTS: The meta
      analysis included five studies and 1,286,752 women for maternal age, six studies
      and 607,822 women for body mass index, and six studies and 1,118,490 women for
      parity. The results of the analysis showed that body mass index >= 25.00 kg/m (OR
      = 1.43, 95% CI [1.40, 1.47]), primiparity of mothers (OR = 1.37, 95% CI [1.35,
      1.40]), and hypertensive disorder in mothers (OR = 1.52, 95% CI [1.43, 1.61]) are
      risk factors for the development of PPH. No rela-tionship was found between
      maternal age >= 35 years and PPH (OR = 1.02, 95% CI [0.99, 1.04]). CONCLUSIONS:
      Midwives, obstetric nurses, and obstetricians should carefully evaluate mothers
      for the risk factors of PPH during the antepartum, intrapartum, and postpartum
      periods. Moreover, at-risk pregnant women should give birth in a unit with
      emergency initiative options. Future studies should examine relevant personal
      characteristics of mothers, as familiarity with the risk factors facilitates the
      management and treatment of PPH. Finally, meta-analyses should review more
      studies to detect risk factors more comprehensively.

PMID- 29219938
TI  - Correlations Among Self-Rated Health, Chronic Disease, and Healthcare Utilization
      in Widowed Older Adults in Taiwan.
AB  - BACKGROUND: Taiwan has a rapidly aging population. It is well known that older
      adults usually have worse health than younger adults, with widowed older adults
      at a particularly high risk of poor health. Widowed older adults experience the
      effects of bereavement, which affects their health. Therefore, health topics
      related to widowed older adults deserve special attention. PURPOSE: The aim of
      this study was to discuss self-rated health for chronic diseases and healthcare
      utilization among widowed older adults. METHODS: A cross-section of data was used
      to analyze self-rated health-related issues. Data were adopted from the National
      Health Interview Survey in Taiwan, with the data on adults aged 65 years and over
      extracted and included in the assessment. Multinomial logistic regression models
      were used to investigate the relationships between healthcare utilization and
      self-rated health and chronic disease variables. RESULTS: The main empirical
      results show worse self-rated health status among widowed older adults in
      comparison with their nonwidowed peers and worse health status for widowers than
      widows. Next, age was negatively correlated with health rating, whereas a
      positive correlation with health was found for education. In addition, chronic
      diseases, particularly stroke, were found to be a significant predictive factor
      related to poor health status. Similar results were observed for healthcare
      utilization, apart from traditional Chinese medicine. Older adults who habitually
      purchased and used traditional Chinese medicine were shown to enjoy relatively
      better health statuses. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: These findings
      identified that chronic diseases and healthcare utilization correlated strongly
      with self-rated health for widowed older adults. Therefore, self-rated health may
      be used as a screening tool by the National Health Insurance System in Taiwan,
      and the results may be referenced by public health officials who are responsible
      for developing welfare strategies to promote healthy aging among the widowed in
      Taiwan.

PMID- 29219939
TI  - Psychometric Evaluation of the Chinese Respiratory Distress Observation Scale on
      Critically Ill Patients With Cardiopulmonary Diseases.
AB  - BACKGROUND: Respiratory distress is a common and distressing experience that
      strikes most critically ill patients with cardiopulmonary diseases. Now, most
      dyspnea assessment tools rely on patient's self-report. Only one instrument, the
      Respiratory Distress Observation Scale (RDOS), is valid for assessing respiratory
      distress when the patient cannot provide a dyspnea self-report. PURPOSE: The aims
      of this study were to develop the Chinese version of RDOS through two-way
      translation and examine its reliability and validity. METHODS: The first step was
      the translation and back-translation to establish the Chinese RDOS and examine
      the semantic equivalence between the back-translation version and the original
      one. The second step was the psychometric testing of the Chinese RDOS including
      internal reliability, interrater reliability, concurrent validity, convergent
      validity, and content and construct validity. RESULTS: The Chinese RDOS was
      reported with an internal consistency (Cronbach's alpha value) of .73, an
      interobserver reliability of .97, and a content validity index of .97. In the
      conscious critically ill patients, significant correlations were found between
      the Chinese RDOS and Spielberger State Anxiety Inventory scores or Dyspnea
      Vertical Visual Analog Scale scores (r = .69 and r = .76, respectively; p <
      .001). In the unconscious critically ill patients, there was a significantly
      positive correlation between the Chinese RDOS scores and fraction of inspiration
      O2 (r = .26, p < .05) and a significantly negative correlation between the
      Chinese RDOS scores and saturation peripheral oxygen (SpO2; r = -.42, p = .001).
      In addition, it also could effectively identify the dyspnea differences between
      the first and last days in the intensive care units (p < .001). CONCLUSIONS: The
      Chinese RDOS showed good reliability and validity in conscious critically ill
      patients. The assessment with the Chinese RDOS could be completed within a short
      period no matter whether the assessor has nursing background in respiratory care
      or not. It could help the professionals systematically manage and track the
      change of respiratory distress in patients.

PMID- 29219940
TI  - Factors Influencing Postpartum Fatigue in Vaginal-Birth Women: Testing a Path
      Model.
AB  - BACKGROUND: Postpartum fatigue is a very common complaint among postpartum women.
      Although current evidence indicates that several factors (e.g., parity, epidural
      analgesia, perineal trauma, perineal pain, and longer second stage of labor) are
      associated with postpartum, not enough is known about the relationships among
      these physical factors simultaneously and how they contribute to the development
      of postpartum fatigue. Increased awareness of the complex relationships among
      these factors will help nurses assess, prevent, and alleviate postpartum fatigue.
      PURPOSE: The aims of this study were to test a model of factors that influence
      postpartum fatigue and to estimate the direct and indirect effects of these
      factors on postpartum fatigue in vaginal-birth women. METHODS: The hypothesized
      model of the factors that influence postpartum fatigue after vaginal birth was
      developed based on previous studies. This study used a cross-sectional
      correlational design and convenience sampling. The Visual Analog Scale for Pain
      was used to measure postpartum perineal pain, and the Postpartum Fatigue Scale
      was used to assess postpartum fatigue via a structured, self-report
      questionnaire. Data analysis included descriptive statistics, Pearson's
      correlation coefficients, and path analysis. RESULTS: This study evaluated 326
      healthy postpartum women within the first day after vaginal birth. Participants
      ranged from 20 to 43 years old, and 50.9% were primiparous. The model of the
      factors influencing postpartum fatigue after vaginal birth showed a good fit with
      the empirical data. Parity and the use of epidural analgesia predicted the
      duration of the second stage of labor, and the degree of perineal trauma
      predicted perineal pain. Participants who had experienced longer durations of the
      second stage of labor and more perineal pain reported higher levels of early
      postpartum fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: It is suggested that
      maternal nurses should better understand postpartum fatigue, take precautions to
      decrease perineal pain, and pay more attention to the longer duration of the
      second stage of labor to minimize postpartum fatigue, increase patient comfort,
      and improve the quality of perinatal care.

PMID- 29219941
TI  - Testing the Psychometric Properties of the Postpartum Sleep Quality Scale in
      Turkish Women.
AB  - BACKGROUND: Postpartum sleeplessness has been observed to be an important health
      problem in Turkey. However, no scale is currently available to evaluate quality
      of sleep in Turkish postpartum women. PURPOSE: The aim of this study was to test
      the validity and reliability of the Turkish Postpartum Sleep Quality Scale (T
      PSQS). METHODS: The sample of this methodological study surveyed 100 women during
      their first 2 postpartum weeks. Data were obtained using a personal
      characteristics form and the PSQS. The PSQS is a 5-point scale ranging from 0 to
      4. The validity of the PSQS was tested using content validity index and
      confirmatory and exploratory factor analyses, and the reliability of the scale
      was tested using Cronbach's alpha. RESULTS: The opinions of eight experts were
      canvassed to test the validity of the T-PSQS. The content validity index showed
      that the scale had high validity (.92). The factor analysis that was conducted to
      test the construct validity of the scale indicated that the scale was composed of
      three factors with eigenvalues over 1.00 and that the total Cronbach's alpha
      coefficient was .88. The Cronbach's alpha for the subscales "Infant night care
      related daytime dysfunction," " Physical symptoms-related sleep inefficiency,"
      and "Sleep quality or sleep" were .82, .86, and .80, respectively. CONCLUSIONS:
      Content validity, construct validity, and reliability analyses of the T-PSQS
      revealed that the scale may be used to measure postpartum sleeplessness levels
      and sleep quality in Turkish women.

PMID- 29219942
TI  - The New Order at the Journal of Pediatric Orthopaedics.

PMID- 29219943
TI  - Replacement of Sedentary Time with Physical Activity: Effect on Lipoproteins.
AB  - PURPOSE: Limited data on the relationship between physical activity and
      lipoprotein particle profiles exist. Our objective was to investigate
      associations between objectively measured physical activity and lipoprotein
      particle size and number, and specifically whether substituting daily sedentary
      behavior with light activity or moderate-to-vigorous physical activity (MVPA) is
      associated with beneficial alterations to the lipoprotein profile among adults
      and those at increased cardiometabolic risk (obese and insulin-resistant
      subjects). METHODS: Sedentary behavior and physical activity intensity and
      duration were measured for 7 consecutive days using the GENEActiv accelerometer
      in a cross-sectional adult cohort (n = 396; mean age, 59.6 +/- 5.5 yr).
      Lipoprotein particle size and subclass concentrations were determined using
      nuclear magnetic resonance spectroscopy. Isotemporal substitution regression
      modeling quantified the associations between replacing 30 min.d of sedentary
      behavior with equal amounts of light activity and MVPA on lipoprotein profiles.
      RESULTS: Daily duration of MVPA was inversely associated with large VLDL
      particles and lipoprotein insulin resistance scores (P < 0.05, after adjustment
      for sedentary time and other confounding factors). Reallocating 30 min of
      sedentary time with MVPA, but not light activity, was associated with less large
      VLDL particles resulting in more favorable average VLDL particle size and
      improved lipoprotein insulin resistance score (P < 0.05). Analysis of high
      cardiometabolic-risk groups revealed similar beneficial alterations to VLDL
      profiles (P < 0.05) with substitution of sedentary time for MVPA among the
      insulin-resistant (homeostasis model assessment for insulin resistance >=75th
      percentile) but not the obese (body mass index >=30 kg.m) individuals.
      CONCLUSIONS: Daily MVPA duration and theoretical replacement of sedentary time
      with MVPA, but not light activity, were associated with less atherogenic VLDL
      profiles, particularly among the insulin-resistant individuals. These findings,
      which require further investigation, highlight the need to develop physical
      activity interventions aimed at improving atherogenic dyslipidemia and lowering
      cardiometabolic risk.

PMID- 29219944
TI  - Minimally Invasive Surgical Pulmonary Embolectomy: A Potential Alternative to
      Conventional Sternotomy.
AB  - OBJECTIVE: Surgical pulmonary embolectomy has gained increasing popularity over
      the past decade with multiple series reporting excellent outcomes in the
      treatment of submassive pulmonary embolism. However, a significant barrier to the
      broader adoption of surgical pulmonary embolectomy remains the large incision and
      long recovery after a full sternotomy. We report the safety and efficacy of using
      a minimally invasive approach to surgical pulmonary embolectomy. METHODS: All
      consecutive patients undergoing surgical pulmonary embolectomy for a submassive
      pulmonary embolism (2015-2017) were reviewed. Patients were stratified as
      conventional or minimally invasive. The minimally invasive approach included a 5-
      to 7-cm skin incision with upper hemisternotomy to the third intercostal space.
      The primary outcomes were in-hospital and 90-day survival. RESULTS: Thirty
      patients (conventional = 20, minimally invasive = 10) were identified. Operative
      time was similar between the two groups, but cardiopulmonary bypass time was
      significantly longer in the minimally invasive group (58 vs 94 minutes, P =
      0.04). While ventilator time and intensive care unit length of stay were similar
      between groups, hospital length of stay was 4.5 days shorter in the minimally
      invasive group, and there was a trend toward less blood product use. In-hospital
      and 90-day survival was 100%. Within the minimally invasive cohort, median right
      ventricular dysfunction at discharge was none-mild and no patient experienced
      postoperative renal failure, deep sternal wound infection, sepsis, or stroke.
      CONCLUSIONS: Minimally invasive surgical pulmonary embolectomy appears to be a
      feasible approach in the treatment of patients with a submassive pulmonary
      embolism. A larger, prospective analysis comparing this modality with
      conventional surgical pulmonary embolectomy may be warranted.

PMID- 29219945
TI  - VATS Plication of the Diaphragm: A Descriptive Observational 10-Year Southampton
      Experience.
AB  - OBJECTIVE: The aim of the study was to report the safety and efficacy of video
      assisted thoracoscopic (VATS) plication of the diaphragm at our institution
      between 2006 and 2016. METHODS: Adult patients selected on etiology and
      combination of investigations including plain chest x-ray, computed tomography of
      chest and abdomen, lung functions in supine and sitting positions,
      radiological/ultrasonic screening for diaphragmatic movement, and phrenic nerve
      conduction studies. We incorporated a triportal VATS and Endostitch device for
      plication, using CO2 insufflation to maximum 12 mm Hg. Bilateral simultaneous
      plication and high-risk patients were electively admitted to intensive therapy
      unit postoperatively. RESULTS: Thirty-five patients (24 males) had their
      diaphragm plicated. The mean age was 56.6 years (range = 23-76 years). The mean
      body mass index was 32.1 (range = 22.2-45.4). Twenty one were right, 13 left, 2
      patients had VATS simultaneous bilateral plication, and 1 had sequential VATS
      bilateral plication. Paralysis was idiopathic in 17, posttraumatic in 5,
      postremoval of mediastinal tumor in 4, and postcardiac surgery in 3. All patients
      presented with lifestyle-limiting dyspnea and orthopnea, three were on nocturnal
      noninvasive ventilation. Five were diabetic and 16 were smokers. The mean supine
      forced expiratory volume in the first second was 62.5% of predicted. Twenty two
      were performed by VATS (63%), three converted to thoracotomy, and 13 were open
      limited thoracotomy (historic). The mean hospital stay was 4.5 days (range = 1
      18, mode 2 days). Intensive therapy unit admission was required in six patients
      for mechanical ventilation 0 to 3 days. Five patients (14%) had no improvement in
      symptoms. There were no deaths, no 30-day readmissions, and no long-term
      neuralgia in this series. CONCLUSIONS: We found minimal access VATS plication of
      the diaphragm to be feasible and safe, but no firm conclusions should be drawn
      from our limited resources. We report the feasibility of concomitant bilateral
      VATS plication of the diaphragm in two adults, and this was not previously
      reported in the adult population. There is a need for further good quality,
      prospective studies, and randomized controlled studies evaluating efficacy of
      VATS diaphragmatic plication.

PMID- 29219946
TI  - C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic
      myeloid leukemia cells in vitro.
AB  - 4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that
      is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and
      antitumor action. In this study we investigated the relationship between C1206
      induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence
      quenching experiments showed that C1206 seemed to bind the middle dimerization
      domain of Hsp90. The interaction between C1206 and Hsp90 was driven mainly by
      electrostatic interaction. In in vitro enzyme activity assay, C1206 dose
      dependently inhibited Hsp90 ATPase activity with an IC50 value of 4.17 MUmol/L.
      In both imatinib-sensitive K562 chronic myeloid leukemia cells and imatinib
      resistant K562/G01 chronic myeloid leukemia cells, C1206 (0.4-3.2 MUmol/L) dose
      dependently caused the degradation of Hsp90 client proteins and downstream
      proteins (AKT, MEK, ERK, C-RAF, P-AKT, P-MEK and P-ERK). Furthermore, C1206 (0.4
      3.2 MUmol/L) dose-dependently induced apoptosis of K562 and K562/G01 cells
      through triggering mitochondrial pathway. Consistent with this result, C1206
      inhibited the proliferation of K562 and K562/G01 cells with IC50 values of 1.10
      and 0.60 MUmol/L, respectively. These results suggest that C1206 is a novel Hsp90
      inhibitor and a promising therapeutic agent for chronic myeloid leukemia.

PMID- 29219947
TI  - Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to
      BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells.
AB  - Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major
      depression. In the brains of depression patients, DCNP1 is up-regulated. However,
      how DCNP1 participates in the pathogenesis of major depression remains unknown.
      In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated
      that the full-length DCNP1 protein was localized in the nucleus, and RRK (the
      residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion
      form of DCNP1 (DCNP1DeltaRRK) and truncated form (DCNP11-116), each lacking the
      RRK residues, did not show the specific nuclear localization like full-length
      DCNP1 in the cells. A rat glioma cell line C6 can synthesize melatonin, a hormone
      that plays important roles in both sleep and depression. We then revealed that
      transfection of C6 cells with full-length DCNP1 but not DCNP1DeltaRRK or DCNP11
      116 significantly decreased the levels of melatonin. Furthermore, overexpression
      of full-length DCNP1, but not DCNP1DeltaRRK or DCNP11-116, in C6 cells
      significantly decreased both the mRNA and protein levels of N-acetyltransferase
      (NAT), a key enzyme in melatonin synthesis. Full-length DCNP1 but not
      DCNP1DeltaRRK or DCNP11-116 was detected to interact with the Nat promoter and
      inhibited its activity through its E-box motif. Furthermore, full-length DCNP1
      but not the mutants interacted with and repressed the transcriptional activity of
      BMAL1, a transcription factor that transactivates Nat through the E-box motif. In
      conclusion, we have shown that RRK (the residues 117-119) are the NLS responsible
      for DCNP1 nuclear localization. Nuclear DCNP1 represses NAT expression and
      melatonin biosynthesis by interacting with BMAL1 and repressing its
      transcriptional activity. Our study reveals a connection between the major
      depression candidate protein DCNP1, circadian system and melatonin biosynthesis,
      which may contribute to the pathogenesis of depression.

PMID- 29219948
TI  - Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via
      up-regulating HIF-1alpha/VEGF signaling.
AB  - Wound therapy remains a clinical challenge due to the complexity of healing
      pathology and high demand of achieving functional and aesthetically satisfactory
      scars. Newly formed blood vessels are essential for tissue repair since they can
      support cells at the wound site with nutrition and oxygen. In this study, we
      investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional
      Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as
      well as its function in wound therapeutics. Treatment of human umbilical vein
      endothelial cells (HUVECs) with ASA VI (20-80 MUg/mL) dose-dependently promoted
      the proliferation, migration and enhanced their angiogenic ability in vitro,
      which were associated with the up-regulated HIF-1alpha/VEGF signaling. Full
      thickness cutaneous wound model rats were injected with ASA VI (20 mg.kg-1.d-1,
      iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound
      healing, and more blood vessels were observed in the regenerated tissue. Due to
      rapid vascularization, the cellular proliferation status, granulation tissue
      formation, collagen matrix deposition and remodeling processes were all
      accelerated, resulting in efficient wound healing. In summary, ASA VI promotes
      angiogenesis of HUVECs in vitro via up-regulating the HIF-1alpha/VEGF pathway,
      and efficiently enhances the vascularization in regenerated tissue and
      facilitates wound healing in vivo. The results reveal that ASA VI is a potential
      therapeutic for vessel injury-related wounds.

PMID- 29219949
TI  - A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human
      lung cancer A549 cells in vitro through regulating epithelial-mesenchymal
      transition.
AB  - Cathepsin L (CTSL), a cysteine protease, is closely related to tumor occurrence,
      development, and metastasis, and possibly regulates cancer cell resistance to
      chemotherapy. miRNAs, especially the miR-200 family, have been implicated in drug
      resistant tumors. In this study we explored the relationship of CTSL, miRNA-200c
      and drug resistance, and the potential regulatory mechanisms in human lung cancer
      A549 cells and A549/TAX cells in vitro. A549/TAX cells were paclitaxel-resistant
      A549 cells overexpressing CTSL and characterized by epithelial-mesenchymal
      transition (EMT). We showed that miRNA-200c and CTSL were reciprocally linked in
      a feedback loop in these cancer cells. Overexpression of miRNA-200c in A549/TAX
      cells decreased the expression of CTSL, and enhanced their sensitivity to
      paclitaxel and suppressed EMT, whereas knockdown of miRNA-200c in A549 cells
      significantly increased the expression of CTSL, and decreased their sensitivity
      to paclitaxel and induced EMT. Overexpression of CTSL in A549 cells significantly
      decreased the expression of miRNA-200c, and reduced their sensitivity to
      paclitaxel and induced EMT, but these effects were reversed by miRNA-200c,
      whereas knockdown of CTSL in A549/TAX cells attenuated paclitaxel resistance and
      remarkably inhibited EMT, but the inhibition of miRNA-200c could reverse these
      effects. Therefore, miRNA-200c may be involved in regulating paclitaxel
      resistance through CTSL-mediated EMT in A549 cells, and CTSL and miRNA-200c are
      reciprocally linked in a feedback loop.

PMID- 29219951
TI  - Comparative study of long-term outcomes of accelerated and conventional collagen
      crosslinking for progressive keratoconus.
AB  - PurposeTo compare the long-term outcomes of accelerated corneal collagen
      crosslinking (CXL) to conventional CXL for progressive keratoconus.Patients and
      methodsComparative clinical study of consecutive progressive keratoconic eyes
      that underwent either accelerated CXL (9 mW/cm2 ultraviolet A (UVA) light
      irradiance for 10 min) or conventional CXL (3 mW/cm2 UVA light irradiance for 30
      min). Eyes with minimum 12 months' follow-up were included. Post-procedure
      changes in keratometry readings (Flat meridian: K1; steep meridian: K2), central
      corneal thickness (CCT), best spectacle-corrected visual acuity (BSCVA), and
      manifest refraction spherical equivalent (MRSE) were analysed.ResultsA total of
      42 eyes were included. In all, 21 eyes had accelerated CXL (20.5+/-5.5 months'
      follow-up) and 21 eyes had conventional CXL group (20.2+/-5.6 months' follow-up).
      In the accelerated CXL group, a significant reduction in K2 (P=0.02), however no
      significant change in K1 (P=0.35) and CCT (P=0.62) was noted. In the conventional
      CXL group, a significant reduction was seen in K1 (P=0.01) and K2 (P=0.04), but
      not in CCT (P=0.95). Although both groups exhibited significant reductions in K2
      readings, no noteworthy differences were noted between them (P=0.36).
      Improvements in BSCVA (accelerated CXL; P=0.22 and conventional CXL; P=0.20) and
      MRSE (accelerated CXL; P=0.97 and conventional CXL; P=0.54) were noted, however
      were not significant in either group.ConclusionAccelerated and conventional CXL
      appear to be effective procedures for stabilising progressive keratoconus in the
      long-term.

PMID- 29219952
TI  - Early onset posterior subscapular cataract in a series of myotonic dystrophy type
      2 patients.
AB  - PurposeEarly onset posterior subscapular cataract (<50 years of age) is a
      characteristic feature of myotonic dystrophy type 2 (DM2). Nevertheless, despite
      being operated at a young age, many patients remain undiagnosed for years. The
      purpose of this study was to assess the prevalence of early onset posterior
      subscapular cataract as a presenting symptom of the disease in a cohort of
      patients with DM2.Patients and methodsWe retrospectively reviewed medical records
      of DM2 patients followed in our institution for the presence of early onset
      posterior subscapular cataract, of any secondary causes of cataract, of the age
      of onset of muscle weakness and of final disease diagnosis.ResultsTwenty-eight
      patients were studied. Nine patients (32.1%) had presented early onset posterior
      subscapular cataract at a median age of 43 years (IQR=36-46) and seven (25%)
      reported it was the presenting sign. No patient was referred for neuromuscular
      evaluation due to the occurrence of early onset cataract. Median delay between
      cataract onset and referral for neuromuscular evaluation was 10 years (IQR=6.0
      19.5) and final DM2 diagnosis was achieved after a median of 16 years (IQR=6.5
      19.5).ConclusionThis study shows that early onset posterior subscapular cataract
      was the first symptom of the disease in 25% of our DM2 patients. Nevertheless,
      none was suspected of having cataract in the context of DM2, and referral for
      neuromuscular evaluation was made after a long delay and usually following the
      appearance of other symptoms. Ophthalmologists can be the first physicians
      encountering these patients and should have a low threshold for referring them
      for neuromuscular evaluation.

PMID- 29219950
TI  - Exosomes: new molecular targets of diseases.
AB  - Extracellular vesicles (EVs) comprise apoptotic bodies, microvesicles and
      exosomes, and they perform as key regulators in cell-to-cell communication in
      normal as well as diseased states. EVs contain natural cargo molecules, such as
      miRNA, mRNA and proteins, and transfer these functional cargos to neighboring
      cells or more distant cells through circulation. These functionally active
      molecules then affect distinct signaling cascades. The message conveyed to the
      recipient cells is dependent upon the composition of the EV, which is determined
      by the parent cell and the EV biogenesis. Because of their properties such as
      increased stability in circulation, biocompatibility, low immunogenicity and
      toxicity, EVs have drawn attention as attractive delivery systems for
      therapeutics. This review focuses on the functional use of exosomes in therapy
      and the potential advantages and challenges in using exosomes for therapeutic
      purposes.

PMID- 29219954
TI  - Migraine with aura and persistent foramen ovale.
AB  - The association between migraine with aura and persistent foramen ovale (PFO), as
      well as other right-to-left shunts, is described. A hypothesis that might explain
      this association is discussed. Observational studies suggested that when a PFO is
      closed patients who have migraine with aura are usually improved. The Migraine
      Intervention with STARFlex Technology (MIST) Trial was a randomised double-blind
      trial in patients with severe intractable migraine with aura and a moderate-large
      PFO that compared implantation of STARFlex devices with the intention of closing
      their PFO versus a sham procedure. It was hoped that the trial would demonstrate
      whether PFO closure would cure migraine. A series of problems in design and
      execution of the trial are discussed.

PMID- 29219953
TI  - Specific retinal phenotype in early IQCB1-related disease.
AB  - PurposeTo describe the ocular and systemic phenotype in IQCB1-related
      disease.MethodsFour cases (3 males, 1 female) with molecularly confirmed IQCB1
      related disease underwent ophthalmological examination including best-corrected
      visual acuity (BCVA) measurement, fundus evaluation, electroretinography (ERG),
      and spectral-domain optical coherence tomography (SD-OCT). Systemic evaluation
      including abdominal ultrasound was performed in all cases.ResultsBCVA ranged from
      perception of light (Case-2; 1 year) to 20/125 (Case-1; 9 years). Fundus
      evaluation showed whitish or silvery reflex outside the vascular arcades in all
      cases; the reflex was circumferential, irregular and covered at-least 6 clock
      hours at younger ages (3 cases; 1-4 years). The reflex was less conspicuous with
      increasing age (Case-1 (9 years) and Case-4 (20 years)). The peripheral retinal
      SD-OCT scans showed evidence of extensive deposition at the level of retinal
      pigment epithelium with complete absence of overlying photoreceptor outer
      segments and myoid zone. The ERG was non-detectable in all cases. All cases
      harbored biallelic nonsense (p.R364*, p. R455*) or frameshifting (p.M370Yfs*49,
      p.C253Afs*9) mutations in IQCB1. Case-1 additionally had developmental delay,
      hemi-hyperplasia, toe syndactyly, and kidney cysts.ConclusionIQCB1-related
      syndromic or non-syndromic Leber congenital amaurosis (LCA) carries unique
      retinal characteristics which helps differentiate IQCB1-retinopathy from other
      genetic forms of LCA in childhood.

PMID- 29219955
TI  - 'On the capability and nomenclature of the Boston Keratoprosthesis type II'.

PMID- 29219956
TI  - Surgical outcomes of preoperative steroid for rhegmatogenous retinal detachment
      with associated choroidal detachment.
AB  - PurposeTo investigate the effect of preoperative steroid on anatomical and
      functional outcomes of vitrectomy in patients with rhegmatogenous retinal
      detachment with associated choroidal detachment (RRD-CD), a rare but particular
      type of RRD.Patients and methodsThis retrospective cohort study included RRD-CD
      patients at Siriraj Hospital during January 2005 to December 2014. Patients with
      preexisting uveitis or RRD with giant retinal tears were excluded. Preoperative,
      intraoperative, and postoperative data were reviewed and analyzed.ResultsA total
      of 76 patients (76 eyes) with RRD-CD were included: 37 patients without
      preoperative steroid (Group A) and 39 patients with preoperative steroid for a
      median of 7 days (Group B: 34 patients with oral prednisolone (0.5-1 mg/kg/day)
      and 5 patients with 20 or 40 mg of subtenon triamcinolone). The total retinal
      reattachment rate at 3 months after one operation was not different between the
      two groups (59 vs 51%) with adjustment for confounders. The proportion of
      patients with visual acuity (VA) improvement at 3 months was also not different
      (57 vs 54%). Survival analysis revealed that 96% of redetachment cases occurred
      within the first 3 months and redetachment rate was not different between the two
      groups for up to 3 years. However, Group B showed a significant regression
      (partial or complete) of CD prior to operation compared to Group A (82 vs 30%,
      P<0.001).ConclusionPreoperative steroid significantly improved CD before
      vitrectomy, but seemed not to improve the single-operation retinal reattachment
      rate or VA at 3 months when compared to no steroid treatment in RRD-CD patients.

PMID- 29219957
TI  - Anterior chamber lens implantation in vitrectomised eyes.
AB  - PurposeTo investigate long-term visual acuity (VA) outcomes and complication
      rates in vitrectomised eyes undergoing anterior chamber intraocular lens (ACIOL)
      insertion.Patients and methodsA single-centre, retrospective case series
      including all patients who had undergone ACIOL placement at the time of
      vitrectomy surgery or having had previous vitrectomy, between January 2007 and
      January 2013. Patients were identified using an electronic database and paper
      casefile notes were analysed for all patients. Patients were excluded if they had
      <3 months follow-up.ResultsTwo hundred and seventy-one patients were included in
      the analysis. Mean follow-up was 27 months. One hundred and forty-eight patients
      were vitrectomised before ACIOL placement. One hundred and twenty-three patients
      underwent vitrectomy at the time of ACIOL placement. Mean best-corrected visual
      acuity (BCVA) before ACIOL placement was 1.27 LogMar (SD 0.95). Mean BCVA at
      final follow-up was 0.51 LogMar (SD 0.66) (paired-sample T-test P<0.001). Forty
      (15%) patients developed postoperative cystoid macular oedema (CMO). Eighty-seven
      (32%) patients had an intraocular pressure (IOP) rise acutely post ACIOL
      insertion. Fifteen (6%) patients developed corneal decompensation. Five
      subsequently required corneal grafting. Sixteen patients had ACIOL displacement
      or instability requiring further surgery.ConclusionsACIOL insertion after
      vitrectomy is effective. Ninety-two per cent of patients maintained or gained VA,
      comparable to previous studies of ACIOL insertion post complicated cataract
      surgery. Raised IOP was the most frequent complication: 61 patients were on
      topical therapy at most recent follow-up. CMO tended to be acute. Corneal
      decompensation was infrequent.

PMID- 29219958
TI  - Spike in neuroimaging requests following the conviction of the optometrist Honey
      Rose.

PMID- 29219959
TI  - Primary orbital Ewing sarcoma family of tumors: a study of 12 cases.
AB  - PurposeThe purpose of this study is to discuss the clinical presentation,
      management, and outcomes of patients with primary orbital Ewing sarcoma family of
      tumors (ESFTs).Patients and methodsRetrospective study of 12 patients with biopsy
      proven primary orbital ESFT.ResultsThe mean age at presentation of primary
      orbital ESFT was 12 years (median, 8 years; range, 5 months to 28 years). There
      were seven (58%) females and five (42%) males. The presenting complaints included
      proptosis (n=10; 83%) and swelling in the upper eyelid (n=2; 17%). The mean
      duration of symptoms was 9 weeks (median, 5 weeks; range, 2-24 weeks). Tumor
      epicenter was located in the superior orbit (n=6; 50%), lateral orbit (n=3; 25%),
      inferior orbit (n=2; 17%), and medial orbit (n=1; 8%). Computed tomography of the
      orbits revealed predominant bony lesion (n=10; 83%) or isolated soft
      tissue/extraosseous lesion (n=2, 17%). At presentation, extraorbital extension
      was noticed in 10 patients including intra cranial extension (n=7; 58%),
      extension into temporal fossa (n=4; 33%), nasal cavity (n=2; 17%), maxillary
      sinus (n=2; 17%), and ethmoid sinus (n=1, 8%). Systemic metastases at
      presentation was detected in five (42%) patients involving the bone marrow (n=4;
      33%), kidney (n=1; 8%), and retroperitoneal lymphnode (n=1; 8%). Multi-modal
      treatment including a combination of neoadjuvant chemotherapy, excision
      biopsy/debulking, and/or radiotherapy was given. Over a mean follow-up period of
      21 months (median, 7 months; range, 1-152 months), disease-related death occurred
      in 11 (92%) cases.ConclusionPrimary orbital ESFT is aggressive at presentation
      and is associated with poor prognosis.

PMID- 29219960
TI  - Exploring factors predicting changes in patients' expectations and psychosocial
      issues during the course of treatment with intravitreal injections for wet age
      related macular degeneration.
AB  - PurposePatients with wet age-related macular degeneration (AMD) often require
      long courses of treatment. We investigate the psychosocial issues that could
      hinder compliance, including patient expectations of treatment. The aims of this
      study were to explore the factors related to changes in patient expectations,
      pain, and anxiety during treatment.Patients and methodsA structured interview was
      carried out among 50 patients selected from the list attending the AMD unit at
      the Princess Alexandra Eye Pavilion (PAEP). The interview was based on a
      questionnaire. Additionally, a visual analogue scale was created as a tool for
      measuring patient expectations, pain, and anxiety. Data were analysed using
      multinomial regression analysis.ResultsThere were significantly more patients who
      had a fall in expectations (P<0.05) during the course of treatment. A fall in
      expectations was found to be predicted by higher starting expectations
      (P=0.00001), greater decline in visual acuity (P=0.008), and perceived
      deterioration of vision after starting treatment (P=0.013). Of the patients, 32%
      planned to stop attending for further injections. Planning to stop attending was
      correlated with worse final visual acuity (P=0.026, 95% CI). Pain and anxiety
      with intravitreal therapy (IVT) was significantly reduced when patients were
      accompanied to the clinic by a friend or relative (P<0.01) using Pearson's
      correlation (r=0.597).ConclusionPatients require appropriate counselling at the
      start of a course of treatment to align expectations with perceived treatment
      outcomes in order to improve adherence. Additionally, a large minority of
      patients would consider stopping treatment. Patients' expectations should be
      assessed at relevant time points along a course of treatment.

PMID- 29219961
TI  - Measurement of full-thickness macular hole size using en face optical coherence
      tomography.
AB  - PurposeTo assess the feasibility and interest of measuring macular hole (MH) size
      using en face optical coherence tomography (OCT) compared with manual diameter
      measurements on B-scans.MethodsAmong our previously published series of 100
      patients operated for primary MH, patients whose images were acquired with Cirrus
      5000 HD-OCT (Carl Zeiss Meditec) with a quality signal strength >5/10 were
      included. Three segmentations (internal limiting membrane, horizontal, and
      retinal pigment epithelium (RPE)) were compared for obtaining the most
      appropriate en face image. MH surface areas were measured using ImageJ software.
      Mean diameters calculated from surface areas (diameter=2 * ?(surface area/pi))
      were compared with those measured on B-scans.ResultsNineteen patients were
      included with a mean age of 72+/-8 years (56-86) and a female predominance
      (3/16). The mean absolute difference between horizontal and vertical diameters
      measured on B-scans was of 54+/-47 MUm (0-180) without reaching significance
      (P=0.874). RPE segmentation provided the best en face image and was feasible
      without and with adjustment, respectively, in 79% and 100% (cases with
      vitreomacular traction) of cases. No significant difference in mean diameters was
      observed between those calculated from en face images (435+/-143 MUm (195-693))
      and those measured on horizontal B-scans (426+/-139 MUm (214-705),
      P=0.482).ConclusionMeasuring MH size on en face OCT images is feasible, reliable,
      and eliminates the potential bias related to manual measurements on B-scans. Its
      integration into OCT devices would offer an automated and easy-to-use option for
      clinical practice.

PMID- 29219962
TI  - Predictors of long-term neurological outcomes in non-accidental head injury.
AB  - BackgroundNon-accidental head injury (NAI) is an inflicted injury usually on a
      child, often resulting in long-term neurological impairment and occasionally
      death. This study aimed to investigate the predictive values of acute findings,
      especially ocular, for long-term neurological outcomes.MethodsMedical records
      including retinal images of all children who attended the local Children's
      hospital with a diagnosis of NAI from over a period of 5 years were reviewed and
      data collected via the electronic patient record system. Patient demographics,
      injuries sustained, wide-field digital retinal images, visual acuity and
      sequalae, neurological function, and global function was noted. IBM SPSS software
      program was used for statistical analysis.ResultsOf the 38 patients (24 males, 14
      females), 12 children died acutely from the head injury with the remaining 26
      children available for long-term follow-up. A younger age of injury (P=0.004) was
      the only statistically significant predictor of good neurological outcome as
      compared with absence of macular retinoschisis, unilateral retinal haemorrhage,
      and unilateral subdural haemorrhage. Of the 38 children, 17 children had
      retinoschisis; 9 children with macular retinoschisis died acutely while 4
      suffered a degree of developmental delay and only 4 were developmentally normal
      at the last follow-up. Long-term visual acuity data was available for 18 of the
      26 survivors (range: NPL to Snellen 6/5). A statistical significance was noted
      between retinoschisis and worsened visual acuity (P<0.05).ConclusionsBilateral
      macular retinoschisis on acute presentation of NAI is associated with a seven
      fold and unilateral with a four-fold increase in the development of a poor
      neurological outcome and eventual death. Conflicting to other studies, younger
      children presented better neurological outcomes.

PMID- 29219963
TI  - Biotechnological mass production of DNA origami.
AB  - DNA nanotechnology, in particular DNA origami, enables the bottom-up self
      assembly of micrometre-scale, three-dimensional structures with nanometre-precise
      features. These structures are customizable in that they can be site-specifically
      functionalized or constructed to exhibit machine-like or logic-gating behaviour.
      Their use has been limited to applications that require only small amounts of
      material (of the order of micrograms), owing to the limitations of current
      production methods. But many proposed applications, for example as therapeutic
      agents or in complex materials, could be realized if more material could be used.
      In DNA origami, a nanostructure is assembled from a very long single-stranded
      scaffold molecule held in place by many short single-stranded staple
      oligonucleotides. Only the bacteriophage-derived scaffold molecules are amenable
      to scalable and efficient mass production; the shorter staple strands are
      obtained through costly solid-phase synthesis or enzymatic processes. Here we
      show that single strands of DNA of virtually arbitrary length and with virtually
      arbitrary sequences can be produced in a scalable and cost-efficient manner by
      using bacteriophages to generate single-stranded precursor DNA that contains
      target strand sequences interleaved with self-excising 'cassettes', with each
      cassette comprising two Zn2+-dependent DNA-cleaving DNA enzymes. We produce all
      of the necessary single strands of DNA for several DNA origami using shaker-flask
      cultures, and demonstrate end-to-end production of macroscopic amounts of a DNA
      origami nanorod in a litre-scale stirred-tank bioreactor. Our method is
      compatible with existing DNA origami design frameworks and retains the modularity
      and addressability of DNA origami objects that are necessary for implementing
      custom modifications using functional groups. With all of the production and
      purification steps amenable to scaling, we expect that our method will expand the
      scope of DNA nanotechnology in many areas of science and technology.

PMID- 29219964
TI  - Greater future global warming inferred from Earth's recent energy budget.
AB  - Climate models provide the principal means of projecting global warming over the
      remainder of the twenty-first century but modelled estimates of warming vary by a
      factor of approximately two even under the same radiative forcing scenarios.
      Across-model relationships between currently observable attributes of the climate
      system and the simulated magnitude of future warming have the potential to inform
      projections. Here we show that robust across-model relationships exist between
      the global spatial patterns of several fundamental attributes of Earth's top-of
      atmosphere energy budget and the magnitude of projected global warming. When we
      constrain the model projections with observations, we obtain greater means and
      narrower ranges of future global warming across the major radiative forcing
      scenarios, in general. In particular, we find that the observationally informed
      warming projection for the end of the twenty-first century for the steepest
      radiative forcing scenario is about 15 per cent warmer (+0.5 degrees Celsius)
      with a reduction of about a third in the two-standard-deviation spread (-1.2
      degrees Celsius) relative to the raw model projections reported by the
      Intergovernmental Panel on Climate Change. Our results suggest that achieving any
      given global temperature stabilization target will require steeper greenhouse gas
      emissions reductions than previously calculated.

PMID- 29219965
TI  - Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns.
AB  - Self-assembled DNA nanostructures enable nanometre-precise patterning that can be
      used to create programmable molecular machines and arrays of functional
      materials. DNA origami is particularly versatile in this context because each DNA
      strand in the origami nanostructure occupies a unique position and can serve as a
      uniquely addressable pixel. However, the scale of such structures has been
      limited to about 0.05 square micrometres, hindering applications that demand a
      larger layout and integration with more conventional patterning methods.
      Hierarchical multistage assembly of simple sets of tiles can in principle
      overcome this limitation, but so far has not been sufficiently robust to enable
      successful implementation of larger structures using DNA origami tiles. Here we
      show that by using simple local assembly rules that are modified and applied
      recursively throughout a hierarchical, multistage assembly process, a small and
      constant set of unique DNA strands can be used to create DNA origami arrays of
      increasing size and with arbitrary patterns. We illustrate this method, which we
      term 'fractal assembly', by producing DNA origami arrays with sizes of up to 0.5
      square micrometres and with up to 8,704 pixels, allowing us to render images such
      as the Mona Lisa and a rooster. We find that self-assembly of the tiles into
      arrays is unaffected by changes in surface patterns on the tiles, and that the
      yield of the fractal assembly process corresponds to about 0.95m - 1 for arrays
      containing m tiles. When used in conjunction with a software tool that we
      developed that converts an arbitrary pattern into DNA sequences and experimental
      protocols, our assembly method is readily accessible and will facilitate the
      construction of sophisticated materials and devices with sizes similar to that of
      a bacterium using DNA nanostructures.

PMID- 29219966
TI  - Gigadalton-scale shape-programmable DNA assemblies.
AB  - Natural biomolecular assemblies such as molecular motors, enzymes, viruses and
      subcellular structures often form by self-limiting hierarchical oligomerization
      of multiple subunits. Large structures can also assemble efficiently from a few
      components by combining hierarchical assembly and symmetry, a strategy
      exemplified by viral capsids. De novo protein design and RNA and DNA
      nanotechnology aim to mimic these capabilities, but the bottom-up construction of
      artificial structures with the dimensions and complexity of viruses and other
      subcellular components remains challenging. Here we show that natural assembly
      principles can be combined with the methods of DNA origami to produce gigadalton
      scale structures with controlled sizes. DNA sequence information is used to
      encode the shapes of individual DNA origami building blocks, and the geometry and
      details of the interactions between these building blocks then control their copy
      numbers, positions and orientations within higher-order assemblies. We illustrate
      this strategy by creating planar rings of up to 350 nanometres in diameter and
      with atomic masses of up to 330 megadaltons, micrometre-long, thick tubes
      commensurate in size to some bacilli, and three-dimensional polyhedral assemblies
      with sizes of up to 1.2 gigadaltons and 450 nanometres in diameter. We achieve
      efficient assembly, with yields of up to 90 per cent, by using building blocks
      with validated structure and sufficient rigidity, and an accurate design with
      interaction motifs that ensure that hierarchical assembly is self-limiting and
      able to proceed in equilibrium to allow for error correction. We expect that our
      method, which enables the self-assembly of structures with sizes approaching that
      of viruses and cellular organelles, can readily be used to create a range of
      other complex structures with well defined sizes, by exploiting the modularity
      and high degree of addressability of the DNA origami building blocks used.

PMID- 29219967
TI  - Primordial clays on Mars formed beneath a steam or supercritical atmosphere.
AB  - On Mars, clay minerals are widespread in terrains that date back to the Noachian
      period (4.1 billion to 3.7 billion years ago). It is thought that the Martian
      basaltic crust reacted with liquid water during this time to form hydrated clay
      minerals. Here we propose, however, that a substantial proportion of these clays
      was formed when Mars' primary crust reacted with a dense steam or supercritical
      atmosphere of water and carbon dioxide that was outgassed during magma ocean
      cooling. We present experimental evidence that shows rapid clay formation under
      conditions that would have been present at the base of such an atmosphere and
      also deeper in the porous crust. Furthermore, we explore the fate of a primordial
      clay-rich layer with the help of a parameterized crustal evolution model; we find
      that the primordial clay is locally disrupted by impacts and buried by impact
      ejected material and by erupted volcanic material, but that it survives as a
      mostly coherent layer at depth, with limited surface exposures. These exposures
      are similar to those observed in remotely sensed orbital data from Mars. Our
      results can explain the present distribution of many clays on Mars, and the
      anomalously low density of the Martian crust in comparison with expectations.

PMID- 29219969
TI  - Scientists want in on humanity's next big space station.

PMID- 29219970
TI  - Grows well in sun and warmth - and shade and cold.

PMID- 29219968
TI  - Programmable self-assembly of three-dimensional nanostructures from 10,000 unique
      components.
AB  - Nucleic acids (DNA and RNA) are widely used to construct nanometre-scale
      structures with ever increasing complexity, with possible application in fields
      such as structural biology, biophysics, synthetic biology and photonics. The
      nanostructures are formed through one-pot self-assembly, with early kilodalton
      scale examples containing typically tens of unique DNA strands. The introduction
      of DNA origami, which uses many staple strands to fold one long scaffold strand
      into a desired structure, has provided access to megadalton-scale nanostructures
      that contain hundreds of unique DNA strands. Even larger DNA origami structures
      are possible, but manufacturing and manipulating an increasingly long scaffold
      strand remains a challenge. An alternative and more readily scalable approach
      involves the assembly of DNA bricks, which each consist of four short binding
      domains arranged so that the bricks can interlock. This approach does not require
      a scaffold; instead, the short DNA brick strands self-assemble according to
      specific inter-brick interactions. First-generation bricks used to create three
      dimensional structures are 32 nucleotides long, consisting of four eight
      nucleotide binding domains. Protocols have been designed to direct the assembly
      of hundreds of distinct bricks into well formed structures, but attempts to
      create larger structures have encountered practical challenges and had limited
      success. Here we show that DNA bricks with longer, 13-nucleotide binding domains
      make it possible to self-assemble 0.1-1-gigadalton, three-dimensional
      nanostructures from tens of thousands of unique components, including a 0.5
      gigadalton cuboid containing about 30,000 unique bricks and a 1-gigadalton
      rotationally symmetric tetramer. We also assembled a cuboid that contains around
      10,000 bricks and about 20,000 uniquely addressable, 13-base-pair 'voxels' that
      serves as a molecular canvas for three-dimensional sculpting. Complex, user
      prescribed, three-dimensional cavities can be produced within this molecular
      canvas, enabling the creation of shapes such as letters, a helicoid and a teddy
      bear. We anticipate that with further optimization of structure design, strand
      synthesis and assembly procedure even larger structures could be accessible,
      which could be useful for applications such as positioning functional components.

PMID- 29219971
TI  - A celebration of Spain's exemplary lab leaders.

PMID- 29219973
TI  - Vivid views of the PINK1 protein.

PMID- 29219974
TI  - Arctic fishing, robot explorers and Chinese medicines.

PMID- 29219975
TI  - Frank Brown (1943-2017).

PMID- 29219976
TI  - US science gender gap unpicked.

PMID- 29219977
TI  - Papers to patents.

PMID- 29219978
TI  - Use machine learning to find energy materials.

PMID- 29219979
TI  - Great mentoring is key for the next generation of scientists.

PMID- 29219980
TI  - A guide to the Nature Index.

PMID- 29219981
TI  - A test drive of a DNA-analysis toolkit in the cloud.

PMID- 29219982
TI  - India's commitment to science begins to pay off.

PMID- 29219984
TI  - Muscle-cell manoeuvres.

PMID- 29219985
TI  - Wanted: academics wise to the needs of government.

PMID- 29219986
TI  - Gauging the risk from US nuclear waste.

PMID- 29219987
TI  - A firm shift.

PMID- 29219988
TI  - A steamy proposal for Martian clays.

PMID- 29219989
TI  - Huge haul of rare pterosaur eggs excites palaeontologists.

PMID- 29219990
TI  - Bat cave solves mystery of deadly SARS virus - and suggests new outbreak could
      occur.

PMID- 29219991
TI  - In good company.

PMID- 29219992
TI  - Outsourcing discovery.

PMID- 29219995
TI  - Two-dimensional tellurium.

PMID- 29219994
TI  - Gene-drive technology needs thorough scrutiny.

PMID- 29219996
TI  - Help wanted: industry seeks science alliances.

PMID- 29219997
TI  - Six principles for energy innovation.

PMID- 29219998
TI  - Corporates make reluctant partners.

PMID- 29220000
TI  - Industry links boost research output.

PMID- 29220001
TI  - Hundreds of German universities set to lose access to Elsevier journals.

PMID- 29220002
TI  - A tip of the hat to evolutionary change.

PMID- 29220003
TI  - Celebrate results of German excellence initiative.

PMID- 29220004
TI  - Lost opportunities.

PMID- 29220005
TI  - Quantum-teleportation experiments turn 20.

PMID- 29220006
TI  - Save Iran's cheetah from extinction.

PMID- 29220007
TI  - DNA self-assembly scaled up.

PMID- 29220008
TI  - Scrap very useless qualifiers in research papers.

PMID- 29220009
TI  - Carbon belts and chains aid nanotech resurgence.

PMID- 29220010
TI  - Archaeologists uneasy as Trump shrinks Bears Ears monument lands.

PMID- 29220011
TI  - The labs that forge distant planets here on Earth.

PMID- 29220012
TI  - First among equals.

PMID- 29220015
TI  - Drug pipeline 3Q17.

PMID- 29220013
TI  - Corrigendum: In vivo genome editing and organoid transplantation models of
      colorectal cancer and metastasis.
AB  - This corrects the article DOI: 10.1038/nbt.3836.

PMID- 29220016
TI  - Recent patents in xenotransplantation.

PMID- 29220017
TI  - Will inter partes review speed US generic drug entry?

PMID- 29220018
TI  - Ablynx's nanobody fragments go places antibodies cannot.

PMID- 29220019
TI  - Amgen cholesterol antibody feud could kill key IP rule.

PMID- 29220022
TI  - Around the world in a month.

PMID- 29220020
TI  - Microbial synthesis of medium-chain chemicals from renewables.
AB  - Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as
      well as commodity and specialty chemicals. As industrial microbes do not contain
      pathways to produce medium-chain chemicals, approaches such as overexpression of
      endogenous enzymes or deletion of competing pathways are not available to the
      metabolic engineer; instead, fatty acid synthesis and reversed beta-oxidation are
      manipulated to synthesize medium-chain chemical precursors. Even so, chain
      lengths remain difficult to control, which means that purification must be used
      to obtain the desired products, titers of which are typically low and rarely
      exceed milligrams per liter. By engineering the substrate specificity and
      activity of the pathway enzymes that generate the fatty acyl intermediates and
      chain-tailoring enzymes, researchers can boost the type and yield of medium-chain
      chemicals. Development of technologies to both manipulate chain-tailoring enzymes
      and to assay for products promises to enable the generation of g/L yields of
      medium-chain chemicals.

PMID- 29220023
TI  - Corrigendum: Development and function of human innate immune cells in a humanized
      mouse model.

PMID- 29220024
TI  - MAGE in yeast is a go.

PMID- 29220025
TI  - California cracks down on stem cell cowboys.

PMID- 29220026
TI  - A new crop of microbe startups raises big bucks, takes on the establishment.

PMID- 29220027
TI  - When pig organs will fly.

PMID- 29220028
TI  - Erratum: Revisiting the Warnock rule.
AB  - This corrects the article DOI: 10.1038/nbt.4015.

PMID- 29220030
TI  - Methods, preprints and papers.

PMID- 29220029
TI  - Corrigendum: Shotgun metagenomics, from sampling to analysis.
AB  - This corrects the article DOI: 10.1038/nbt.3935.

PMID- 29220031
TI  - Activists bury India's GM mustard hopes.

PMID- 29220032
TI  - Institutional culture is the key to team science.

PMID- 29220033
TI  - Challenges and recommendations for epigenomics in precision health.

PMID- 29220035
TI  - The Broad and Johns Hopkins lure deep-pocketed investors.

PMID- 29220034
TI  - Just how good an investment is the biopharmaceutical sector?
AB  - Uncertainty surrounding the risk and reward of investments in biopharmaceutical
      companies poses a challenge to those interested in funding such enterprises.
      Using data on publicly traded stocks, we track the performance of 1,066
      biopharmaceutical companies from 1930 to 2015-the most comprehensive financial
      analysis of this sector to date. Our systematic exploration of methods for
      distinguishing biotech and pharmaceutical companies yields a dynamic, more
      accurate classification method. We find that the performance of the biotech
      sector is highly sensitive to the presence of a few outlier companies, and
      confirm that nearly all biotech companies are loss-making enterprises, exhibiting
      high stock volatility. In contrast, since 2000, pharmaceutical companies have
      become increasingly profitable, with risk-adjusted returns consistently
      outperforming the market. The performance of all biopharmaceutical companies is
      subject not only to factors arising from their drug pipelines (idiosyncratic
      risk), but also from general economic conditions (systematic risk). The risk
      associated with returns has profound implications both for patterns of investment
      and for funding innovation in biomedical R&D.

PMID- 29220037
TI  - Corrections.

PMID- 29220036
TI  - The international MAQC Society launches to enhance reproducibility of high
      throughput technologies.

PMID- 29220038
TI  - Top 20 translational researchers of 2016.

PMID- 29220039
TI  - Robotic lobectomy: revolution or evolution?

PMID- 29220040
TI  - From manual to robotic video-assisted resection of posterior mediastinal masses.

PMID- 29220041
TI  - Robotic assisted minimally invasive esophagectomy for esophageal cancer: a
      comment on the Ruijin hospital experience.

PMID- 29220042
TI  - Robotic portal lobectomy, surgery through a virtual thoracotomy.

PMID- 29220043
TI  - Robotic-assisted thoracic surgery: a helpful tool or just another expensive
      gadget?

PMID- 29220044
TI  - Low coordinated mononuclear erbium(iii) single-molecule magnets with C3v
      symmetry: a method for altering single-molecule magnet properties by
      incorporating hard and soft donors.
AB  - Structures and magnetic characteristics of two three-coordinate erbium(iii)
      compounds with C3v geometry, tris(2,6-di-tert-butyl-p-cresolate)erbium, Er(dbpc)3
      (1) and tris(bis(trimethylsilyl)methyl)erbium, Er(btmsm)3 (2), were determined.
      Both underwent temperature-dependent slow magnetic relaxation processes in the
      absence of an external magnetic field. As a result of the differences in the
      coordination environment, they exhibit different energy barriers and quantum
      tunneling of magnetization (QTM) constants.

PMID- 29220045
TI  - Molecular dynamics studies of irradiation effects on hydrogen isotope diffusion
      through nickel crystals and grain boundaries.
AB  - Experiments indicated that tritium permeation in 316 austenitic stainless steel
      is enhanced by a factor of ~2-5 after irradiation as compared to the ex-reactor
      results. To understand this enhancement, we have performed extensive molecular
      dynamics simulations to study the effects of both the grain boundary structure
      (Sigma3{111}, Sigma5{100} and Sigma11{311}) and the nature of point defects
      (vacancy, interstitial, and Frenkel pair) on hydrogen diffusivities in an
      exemplar fcc metal (nickel). By deriving diffusivities from mean square
      displacement, all possible atomic jump paths encountered during real diffusion
      are realistically sampled. By performing extremely long simulations, the
      statistical errors typically associated with this method are also significantly
      reduced. We found that within grains, interstitial defects increase diffusivity
      whereas vacancies have almost no effects. This mechanism might explain hydrogen
      permeation enhancements in irradiated materials with coarse grains. The largest
      increase in hydrogen diffusivity was found at a certain combination of grain
      boundary and point defect. This suggests that permeability of materials with
      finer grains can also be enhanced by irradiation depending on whether the grain
      boundary character is skewed. Our results shed new light on the enhancement of
      tritium permeation in 316 stainless steels during reactor operations.

PMID- 29220046
TI  - Au70S20(PPh3)12: an intermediate sized metalloid gold cluster stabilized by the
      Au4S4 ring motif and Au-PPh3 groups.
AB  - Reducing (Ph3P)AuSC(SiMe3)3 with l-Selectride(r) gives the medium-sized metalloid
      gold cluster Au70S20(PPh3)12. Computational studies show that the phosphine bound
      Au-atoms not only stabilize the electronic structure of Au70S20(PPh3)12, but also
      behave as electron acceptors leading to auride-like gold atoms on the exterior.

PMID- 29220047
TI  - A bonding evolution analysis for the thermal Claisen rearrangement: an
      experimental and theoretical exercise for testing the electron density flow.
AB  - A comprehensive theoretical investigation of the thermal Claisen rearrangement of
      allyl vinyl ether (AVE) to allylacetaldehyde has been carried out. We present the
      use of the electron localization function (ELF) to monitor the bonding evolution
      aspects in the course of this thermal rearrangement and the results are compared
      with a photo-impulsive process where instantaneous vibration frequencies are
      monitored [I. Iwakura, Phys. Chem. Chem. Phys., 2011, 12, 5546-5555]. Our results
      reveal an asynchronous electron density rearrangement inasmuch that the breaking
      of the C3-O bond and the formation of C1-C5 do not take place simultaneously. We
      also demonstrate how the bonding evolution brings about the natural appearance of
      the curly arrows representing the electronic flow in molecular rearrangements.
      This holds the key to gaining an unprecedented insight into the mapping of the
      electron density flow while the bonds change throughout the reaction progress.

PMID- 29220048
TI  - Photokinetic study on remarkable excimer phosphorescence from heteroleptic
      cyclometalated platinum(ii) complexes bearing a benzoylated 2-phenylpyridinate
      ligand.
AB  - Novel heteroleptic cyclometalated platinum(ii) complexes consisting of 5'
      benzoylated 2-phenylpyridinate (ppy) cyclometalated and acetylacetonate ancillary
      ligands were synthesized, and their photoluminescence (PL) properties were
      investigated. The 5'-benzoylated complex without any other substituents exhibited
      phosphorescence-based monomer emission at 479 nm in dichloromethane (10 MUM, rt)
      with a PL quantum yield of 0.28. On the other hand, in poly(methyl methacrylate)
      (PMMA) film, remarkable excimer emission additionally emerged at ca. 600 nm with
      a relatively high PL quantum yield of 0.47 as the doping level increased to 0.20
      mmmol g-1, which was comparably intense in comparison with the monomer emission.
      In the case of the complexes with unsubstituted, 4'-benzoylated, and 5'
      fluorinated ppy cyclometalated ligands, excimer emission was modestly generated
      at the same doping level, and thus the introduction of a benzoyl group to the 5'
      position is effective to obtain remarkable excimer emission. The combination of
      benzoyl and fluoro groups was more effective at inducing excimer emission, and
      the intensity of excimer emission of the 2-(5-benzoyl-4,6
      difluorophenyl)pyridinate-based complex was 3.5 times larger than that of monomer
      emission at a doping level of 0.20 mmmol g-1 in PMMA. From the analysis of PL
      lifetimes at varying concentrations, photokinetic profiles were fully analyzed
      according to the model system for the irreversible excimer formation, and the
      excimer formation rate constant of the 5'-benzoylated complex was determined in
      dichloromethane as 2.2 * 109 M-1 s-1, which is 4.4 times larger than that of the
      unsubstituted complex. We also fabricated an organic light-emitting diode using
      the 2-(5-benzoyl-4,6-difluorophenyl)pyridinate-based complex as a single emitter.
      The device exhibited pseudo-white EL with the Commission internationale de
      l'eclairage chromaticity coordinates of (0.42, 0.42).

PMID- 29220049
TI  - Unprecedented NH2-MIL-101(Al)/n-Bu4NBr system as solvent-free heterogeneous
      catalyst for efficient synthesis of cyclic carbonates via CO2 cycloaddition.
AB  - Amine-functionalised framework NH2-MIL-101(Al) was synthesized using a
      solvothermal and microwave method and characterized by PXRD, FT-IR, TGA, SEM-EDX,
      and BET surface area analysis. The desolvated framework, in the presence of co
      catalyst tetrabutylammonium bromide (TBAB), acted as an excellent heterogeneous
      catalyst for the solvent-free cycloaddition of carbon dioxide (CO2) with
      epoxides, affording five-membered cyclic carbonates. Using styrene oxide, the NH2
      MIL-101(Al)/TBAB system showed more than 99% conversion, affording 96% yield and
      99% selectivity with a turn over frequency of 23.5 h-1. This validated the
      synergistic effect of the quaternary ammonium salt during CO2 cycloaddition. The
      catalyst could be recycled at least five times without a noticeable loss in
      activity, while leaching test showed no leached Al3+ ions throughout the
      reaction. Thorough analysis of the reaction parameters showed that the optimum
      conditions for obtaining the maximum yield and highest selectivity were 120 
      degrees C and 18 bar of CO2 for 6 h. The outstanding conversion and selectivity
      were maintained for a range of aliphatic and aromatic epoxides, corroborating the
      duel benefit of the micro-mesoporous system with amine functionality, which
      offered easy access for reactant molecules with diverse sizes, and provided
      inspiration for future CO2 cycloaddition catalytic systems. We also propose a
      rationalized mechanism for the cycloaddition reaction mediated by NH2-MIL-101(Al)
      and TBAB based on literature precedent and experimental outcome.

PMID- 29220050
TI  - A pair of polymorphous metal-organic frameworks based on an angular
      diisophthalate linker: synthesis, characterization and gas adsorption properties.
AB  - The combination of an angular diisophthalate ligand, 5,5'-(naphthyl-2,7
      yl)diisophthalate (H4L), and copper ions under different solvothermal conditions
      afforded two polymorphous metal-organic frameworks (ZJNU-77 and ZJNU-78) with the
      same framework composition of [Cu2(L)(H2O)2], providing a platform to investigate
      the relationship between MOF polymorphism and gas adsorption properties. As
      determined by single-crystal X-ray diffraction, ZJNU-77 and ZJNU-78 exhibited
      three-dimensional networks crystallizing in different space groups. Their
      structural differences were mainly manifested by the ligand's conformation, the
      level of framework interpenetration and the network's topology. Interestingly,
      gas adsorption studies showed that the two compounds after desolvation displayed
      comparable gas adsorption properties with respect to C2H2, CO2 and CH4, despite
      their different surface areas and pore volumes. The C2H2, CO2, and CH4 uptake
      capacities at 298 K and 1 atm are 120.2, 78.1, and 18.4 cm3 (STP) g-1 for ZJNU
      77, and 122.0, 82.0, and 18.9 cm3 (STP) g-1 for ZJNU-78, respectively. The IAST
      adsorption selectivities for the equimolar C2H2/CH4 and CO2/CH4 mixtures are 28.6
      and 5.7 for ZJNU-77, and 28.4 and 5.9 for ZJNU-78 at 298 K and 1 atm. These
      results indicate that besides the surface area, the pore size also plays a
      crucial role in gas adsorption. This work not only represents an intriguing
      example of MOF polymorphism achieved by controlling solvothermal conditions, but
      also provides an insight into the correlation between MOF polymorphism and gas
      adsorption properties.

PMID- 29220051
TI  - Improving extraction and post-purification concentration of membrane proteins.
AB  - Membrane proteins (MPs), despite being critically important drug targets for the
      pharmaceutical industry, are difficult to study due to challenges in obtaining
      high yields of functional protein. Most current extraction efforts use
      specialized non-ionic detergents to solubilize and stabilize MPs, with MPs being
      concentrated by ultrafiltration (UF). However, many detergents are retained
      during the UF step, which can destabilize MPs and/or interfere with their
      characterization. Here, we studied the influence of detergent selection on the
      extraction and UF-based concentration of biomedically-relevant MPs, the light
      driven sodium and chloride transporters, KR2 and halorhodopsin (pHR) which are
      also model proteins for more complex mammalian rhodopsins. We also designed a
      flat-bottomed centrifugal filter that can concentrate MPs with enhanced removal
      of free detergents by promoting concentration polarization (CP). We tested the
      performance of this new filter using four commonly employed MP detergents, octyl
      beta-D maltoside (OM), decyl-beta-D maltoside (DM), dodecyl-beta-D maltoside
      (DDM) and octyl-beta-D glucoside (OG), over a range of detergent and salt
      concentrations. Detergent passage is significantly higher for the flat-bottomed
      filter achieving up to 2-fold greater sieving of detergent in DM-solubilized pHR
      system due to the high degree of CP. We observe more efficient, up to 5-fold
      higher extraction of KR2 in the presence of a longer 12-carbon alkyl chain
      detergent, DDM compared to a shorter 8-carbon detergent, OM. Assuming complete
      binding and elution of the extracted protein, DDM-based extraction of KR2 could
      lead to a potential 7-fold improvement in purification yields compared to
      conventional methods which yield ~1 mg MP per liter of cell culture. However, the
      longer chain detergents like DDM form larger micelles that are difficult to
      remove by UF. Thus, there exists a trade-off between choosing a detergent that
      will enable efficient extraction of MP while showing easier removal during
      subsequent UF. The extraction efficiency and UF-based separation of detergent
      micelles provide insights for other applications involving detergent-mediated
      separation/extraction.

PMID- 29220052
TI  - Hypoglycemic and hypolipidemic effects of anthocyanins extract from black soybean
      seed coat in high fat diet and streptozotocin-induced diabetic mice.
AB  - Black soybean seed coat extract (BSSCE) is a rich source of anthocyanins with
      multiple health effects. This study was aimed at investigating the composition
      and hypoglycemic and hypolipidemic effects of BSSCE in vitro and in a high-fat
      diet and streptozotocin (STZ)-induced diabetic mice. The anthocyanins of BSSCE
      were identified as cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and
      peonidin-3-O-glucoside by HPLC-MS. Results demonstrated that BSSCE exhibited
      strong inhibitory activities for alpha-amylase, potent inhibition activity
      against lipid accumulation in HepG2 cells and protection effect on H2O2-induced
      oxidative stress-damaged HepG2 cells. The food and water intake, body weight
      loss, blood glucose and insulin level of BSSCE treatment group were found to be
      significantly reduced when compared with those of diabetic mice group (p < 0.05).
      The fasting blood glucose level and insulin level of the BSSCE 400 mg kg-1 group
      mice significantly decreased by 47.97% and 46.49%, respectively. The oral glucose
      tolerance and activities of antioxidant enzymes including superoxide dismutase
      (SOD), glutathione peroxidase (GPX) and catalase (CAT) notably improved (p <
      0.05). BSSCE could also ameliorate the atherogenic dyslipidaemia of diabetic mice
      by remarkably decreasing the content of total cholesterol (T-CHO), total
      triglyceride (TG), and non-esterified fatty acid (NEFA) and increasing the
      content of high-density lipoprotein cholesterol (HDL-c) (p < 0.05). BSSCE could
      protect against liver, kidney and pancreas damages in diabetic mice. This study
      suggested that cyanidin-3-O-glucoside contributed to BSSCE-induced hypoglycemia
      and hypolipidemia effects in type 2 diabetes mellitus (T2DM), and BSSCE might be
      a promising functional food or medicine for T2DM treatment.

PMID- 29220053
TI  - The mechanism of reduced IgG/IgE-binding of beta-lactoglobulin by pulsed electric
      field pretreatment combined with glycation revealed by ECD/FTICR-MS.
AB  - Bovine beta-lactoglobulin (beta-Lg) is a major allergen existing in milk and
      causes about 90% of IgE-mediated cow's milk allergies. Previous studies showed
      that pulsed electric field (PEF) treatment could partially unfold the protein,
      which may contribute to the improvement of protein glycation. In this study, the
      effect of PEF pretreatment combined with glycation on the IgG/IgE-binding ability
      and the structure of beta-Lg was investigated. The result showed that PEF
      pretreatment combined with glycation significantly reduced the IgG and IgE
      binding abilities, which was attributed to the changes of secondary and tertiary
      structure and the increase in glycation sites and degree of substitution per
      peptide (DSP) value determined by electron capture dissociation Fourier transform
      ion cyclotron resonance mass spectrometry (ECD/FTICR-MS). Unexpectedly, glycation
      sites (K47, K91 and K135) added by two mannose molecules were identified in
      glycated beta-Lg with PEF pretreatment. Moreover, the results indicated that PEF
      pretreatment at 25 kV cm-1 for 60 MUs promoted the reduction of IgG/IgE-binding
      capacity by increasing the glycation degree of beta-Lg, whereas single PEF
      treatment under the same conditions markedly enhanced the IgG/IgE-binding ability
      by partially unfolding the structure of beta-Lg. The results suggested that
      ECD/FTICR-MS could help us to understand the mechanism of reduction in the
      IgG/IgE-binding of beta-Lg by structural characterization at the molecular level.
      Therefore, PEF pretreatment combined with glycation may provide an alternative
      method for beta-Lg desensitization.

PMID- 29220054
TI  - Experimental and theoretical studies on the NLO properties of two quaternary non
      centrosymmetric chalcogenides: BaAg2GeS4 and BaAg2SnS4.
AB  - New middle and far-infrared (MFIR) nonlinear optical (NLO) chalcogenides have
      been receiving increasing attention for their great importance in military and
      civil fields. In addition, the current challenge in the efforts for identifying a
      promising MFIR NLO material lies in achieving simultaneously large second
      harmonic generation (SHG) intensity and high laser-induced damage threshold
      (LIDT) in the same material. In this study, two quaternary non-centrosymmetric
      (NCS) sulfides, BaAg2GeS4 (1) and BaAg2SnS4 (2), were synthesized from a high
      temperature solid-state reaction using BaCl2 flux in evacuated closed silica
      tubes. Although 1 and 2 show identical stoichiometry, they crystallize in
      different NCS space groups, tetragonal I4[combining macron]2m (no. 121) and
      orthorhombic I222 (no. 23), respectively, based on the results of crystal
      structure solution. In their structures, highly distorted AgS4 tetrahedra
      interconnect together via corner-sharing to form two-dimensional (2D) layers,
      which are further bridged with isolated GeS4 or SnS4 units to produce a three
      dimensional (3D) framework structure with Ba cations lying in the tunnels.
      Remarkably, they not only possess phase-matchable (PM) abilities but also exhibit
      a good balance between strong SHG responses (1.7* and 0.4* AgGaS2) and high LIDTs
      (3.2* and 1.5* AgGaS2). Moreover, theoretical calculations based on density
      functional theory (DFT) methods have aided the understanding of energy bands,
      electronic structures, and linear and NLO properties.

PMID- 29220055
TI  - On-demand acoustic droplet splitting and steering in a disposable microfluidic
      chip.
AB  - On-chip droplet splitting is one of the fundamental droplet-based microfluidic
      unit operations to control droplet volume after production and increase
      operational capability, flexibility, and throughput. Various droplet splitting
      methods have been proposed, and among them the acoustic droplet splitting method
      is promising because of its label-free operation without any physical or thermal
      damage to droplets. Previous acoustic droplet splitting methods faced several
      limitations: first, they employed a cross-type acoustofluidic device that
      precluded multichannel droplet splitting; second, they required irreversible
      bonding between a piezoelectric substrate and a microfluidic chip, such that the
      fluidic chip was not replaceable. Here, we present a parallel-type acoustofluidic
      device with a disposable microfluidic chip to address the limitations of previous
      acoustic droplet splitting devices. In the proposed device, an acoustic field is
      applied in the direction opposite to the flow direction to achieve multichannel
      droplet splitting and steering. A disposable polydimethylsiloxane microfluidic
      chip is employed in the developed device, thereby removing the need for permanent
      bonding and improving the flexibility of the droplet microfluidic device. We
      experimentally demonstrated on-demand acoustic droplet bi-splitting and steering
      with precise control over the droplet splitting ratio, and we investigated the
      underlying physical mechanisms of droplet splitting and steering based on Laplace
      pressure and ray acoustics analyses, respectively. We also demonstrated droplet
      tri-splitting to prove the feasibility of multichannel droplet splitting. The
      proposed on-demand acoustic droplet splitting device enables on-chip droplet
      volume control in various droplet-based microfluidic applications.

PMID- 29220056
TI  - Structural stability and magnetic-exchange coupling in Mn-doped monolayer/bilayer
      MoS2.
AB  - Ferromagnetic (FM) two-dimensional (2D) transition metal dichalcogenides (TMDs)
      have potential applications in modern electronics and spintronics and doping of
      TMDs with transition metals can enhance the magnetic characteristics. In this
      work, the structural stability, electronic states, and magnetic properties of Mn
      doped monolayer/bilayer MoS2 are studied systematically by first-principles
      calculations. Substitutional Mn dopants at the Mo sites are energetically
      favorable in both monolayer and bilayer MoS2 under the S-rich condition which is
      common in the synthesis of MoS2 nanosheets. Two Mn dopants participate in the FM
      interaction in monolayer MoS2 and magnetic coupling of two Mn dopants via the
      double-exchange mechanism can be mediated by the nearest neighboring S. Magnetic
      coupling can be ascribed to the competition between the double-exchange, direct
      exchange, and super-exchange interactions, which take place between two Mn
      dopants in bilayer MoS2 with the MniMnMo, MniMnS and MnMo-MnMo configurations.
      Our results reveal the geometrical dependence of magnetic-exchange coupling
      suggesting that Mn-doped monolayer/bilayer MoS2 has large potential in spintronic
      devices.

PMID- 29220057
TI  - Combining adhesive contact mechanics with a viscoelastic material model to probe
      local material properties by AFM.
AB  - Viscoelastic properties are often measured using probe based techniques such as
      nanoindentation (NI) and atomic force microscopy (AFM). Rarely, however, are
      these methods verified. In this article, we present a method that combines
      contact mechanics with a viscoelastic model (VEM) composed of springs and
      dashpots. We further show how to use this model to determine viscoelastic
      properties from creep curves recorded by a probe based technique. We focus on
      using the standard linear solid model and the generalized Maxwell model of order
      2. The method operates in the range of 0.01 Hz to 1 Hz. Our approach is suitable
      for rough surfaces by providing a defined contact area using plastic pre
      deformation of the material. The very same procedure is used to evaluate AFM
      based measurements as well as NI measurements performed on polymer samples made
      from poly(methyl methacrylate) and polycarbonate. The results of these
      measurements are then compared to those obtained by tensile creep tests also
      performed on the same samples. It is found that the tensile test results differ
      considerably from the results obtained by AFM and NI methods. The similarity
      between the AFM results and NI results suggests that the proposed method is
      capable of yielding results comparable to NI but with the advantage of the
      imaging possibilities of AFM. Furthermore, all three methods allowed a clear
      distinction between PC and PMMA by means of their respective viscoelastic
      properties.

PMID- 29220058
TI  - Revisiting the racemization mechanism of helicenes.
AB  - Herein we propose a general mechanism for the racemization of [n]helicenes up to
      n = 24. It is a concerted process for n = 4-7, but a multi-step mechanism is
      followed for n>= 8, involving 2n- 14 intermediates. The changes in the barriers
      are a delicate consequence of the steric hindrance and the pi-interactions.

PMID- 29220060
TI  - Upper limb ischaemia: a South African single-centre experience.
AB  - OBJECTIVE: The aims of this study were to report on our experience with upper
      limb ischaemia (ULI), to define the pattern and distribution of disease, describe
      key demographic features and report on conventional clinical outcomes. METHODS:
      This was a single-centre, retrospective, descriptive study. All patients (n = 64)
      who underwent a surgical intervention for ULI over a 12-year study period were
      included. Findings were analysed and compared with the current literature.
      RESULTS: A male:female ratio of 0.60 was reported. Two major subgroups of
      patients were identified. The patients in the thrombo-embolic subgroup (n = 30)
      were notably younger than expected (mean age 55 years) compared to those in the
      atherosclerotic occlusive disease subgroup (n = 12, mean age 57 years).
      Presentation overall was generally late, with 8.6% of acute ULI and 48.3% of
      chronic ULI patients presenting with irreversible ischaemia and tissue loss,
      respectively. Thrombo-embolism was the dominant vascular pathology reported in
      this case series (47%). Ninety-five procedures were performed in 64 patients (89
      open, six endovascular). Peri-operative (30-day) mortality rate was 7.8%.
      Systemic and procedure-related complications were observed in 13 and 23%,
      respectively. The overall major amputation rate was 10.9%. Adherence to follow up
      was poor (51% at six months). CONCLUSION: Although few firm conclusions could be
      drawn, this review has expanded our overall perspective of ULI, specific to the
      population we serve. Collaboration between African vascular units should be
      encouraged in an attempt to further define the pattern of ULI by identifying
      distinct geographical confounders.

PMID- 29220059
TI  - Fluorescence detection and removal of copper from water using a biobased and
      biodegradable 2D soft material.
AB  - We have developed a green and robust fluorogenic (lambdaex = 410 nm, lambdaem =
      510 nm) cellulose membrane using graphene oxide (GO) as a construct for
      simultaneous copper ion recognition and filtration at environmentally relevant
      levels. The detection limit and removal limit of Cu2+ are 7.3 * 10-7 M and 1000
      ppm, respectively. The simplicity and scalability achieved for the detection and
      removal of metal ions in waste water is particularly noteworthy given the
      significant problems associated with metal ion pollution of drinking water.

PMID- 29220061
TI  - Comparison of carotid intima-media thickness and coronary artery calcium score
      for estimating subclinical atherosclerosis in patients with fatty liver disease.
AB  - INTRODUCTION: Fatty liver disease (FLD) is correlated with cardiovascular
      disease. Carotid intima-media thickness (CIMT) and coronary artery calcium score
      (CACS) can noninvasively identify subclinical atherosclerosis and predict risk
      for cardiovascular events. This study evaluated CIMT and CACS measurements to
      detect subclinical atherosclerosis in patients with and without FLD. METHODS:
      Patients who underwent carotid and abdominal ultrasounds as well as cardiac
      computed tomography (CT) scans were evaluated retrospectively. The differences
      between the mean CIMT value and CACS measurements in patients with FLD and those
      with normal livers were estimated. RESULTS: Among 819 patients (average age of
      53.3 +/- 11.2 years), 330 had FLD. The CIMT was greater in patients with FLD
      compared to the controls (0.79 +/- 0.17 vs 0.76 +/- 0.17 mm, p = 0.012), and
      carotid plaques were more commonly seen in patients with FLD. The incidence of a
      composite of larger CIMT ( >= 75th percentile) plus plaque presence was higher in
      FLD patients (43.3 vs 36.0%, p = 0.041). Particularly among young patients (<=
      50), the CIMT was larger in patients with FLD than in the controls. FLD increased
      the risk of a composite of large CIMT plus plaque presence in young patients
      (odds ratio 1.92, 95% confidence interval 1.05-3.49, p = 0.034). However,
      patients with FLD had no greater incidence of CACS of over 100 than the controls.
      CONCLUSION: CIMT was a better marker of underlying subclinical atherosclerotic
      risk among patients with FLD than CACS. FLD particularly, increases the risk of
      subclinical atherosclerosis in patients younger than 50 years of age. These
      patients should undergo screening CIMT to detect atherosclerosis and modify risk
      factors.

PMID- 29220062
TI  - Community-Academic Partnership to Implement a Breast and Cervical Cancer
      Screening Education Program in Puerto Rico.
AB  - OBJECTIVE: To describe how a community-academic partnership between Taller Salud
      Inc., a community-based organization, and the Puerto Rico Community Cancer
      Control Outreach Program of the University of Puerto Rico was crucial in the
      adaptation and implementation of Cultivando La Salud (CLS), an evidencebased
      educational outreach program designed to increase breast and cervical cancer
      screening among Hispanic women living in Puerto Rico. This collaboration
      facilitated the review and adaptation of the CLS intervention to improve cultural
      appropriateness, relevance, and acceptability for Puerto Rican women. METHODS: A
      total of 25 interviewers and 12 Lay Health Workers (LHWs) were recruited and
      trained to deliver the program. The interviewers recruited women who were non
      adherent to recommended screening guidelines for both breast and cervical cancer.
      LHWs then provided one-on-one education using the adapted CLS materials. RESULTS:
      A total of 444 women were recruited and 48% of them were educated through this
      collaborative effort. CONCLUSION: Our main accomplishment was establishing the
      academic-community partnership to implement the CLS program. Nevertheless, in
      order to promote better collaborations with our community partners, it is
      important to carefully delineate and establish clear roles and shared
      responsibilities for each partner for the successful execution of research
      activities, taking into consideration the community's needs.

PMID- 29220063
TI  - Preventive Care Screening in the Puerto Rican Geriatric Population: A Formative
      Evaluation of Patient Knowledge.
AB  - OBJECTIVE: This study was meant to be the first step in bridging a gap in the
      literature concerning Puerto Rican geriatric patients' levels of knowledge
      concerning 4 preventive care screening tests: mammography, bone densitometry,
      colonoscopy, and lipid panels. METHODS: Patients 65 years old and older were
      interviewed at the University of Puerto Rico (UPR), Medical Sciences Campus,
      primary care clinics. Fisher's exact test was used to assess knowledge status for
      each screening test. RESULTS: Fifty-three participants, 53% being women, took
      part in the study. All the women (100%) reported having knowledge about
      mammography screening as well as about bone densitometry scans (71%); 91% of the
      participants reported having knowledge concerning colonoscopy. Only 34%
      understood what information results from a lipid panel. The majority of the
      participants were not aware of precisely when each of the screening tests under
      discussion should be undertaken. For all the screenings, level of education and
      provider recommendation were associated with increased levels of knowledge
      (though statistically significant only for bone densitometry and lipid panels).
      CONCLUSION: Elderly Puerto Ricans appear to have knowledge about screening tests;
      however, there is an overall lack of knowledge about the timing of screening.
      Risk factors for this lack of knowledge are having a relatively lower level of
      education, the lack of healthcare-provider recommendation, and the lack of
      patient education. Understanding when to have tests is vital for interventions,
      in order to improve patient outcomes, which can include death from treatable
      conditions or diseases. Future research should include larger samples as well as
      studies of outcomes associated with these screening tests. These will help
      researchers and policymakers better understand this issue and aid in the
      development and implementation of interventions for both patients and physicians.

PMID- 29220065
TI  - Clinical Profile of Patients with Psychogenic Non-epileptic Seizures in Puerto
      Rico.
AB  - OBJECTIVE: Specialized epilepsy clinics receive many cases (20%-30% of total
      cases) in which the patients are diagnosed with psychogenic non-epileptic
      seizures (PNES). In Puerto Rico, there has been a lack of research on and data
      about patients with PNES. This study examined the clinical profile of 34 patients
      with a confirmed diagnosis of PNES. METHODS: A secondary analysis of 34 clinical
      records of patients with PNES was conducted. The resulting profile was based on
      clinical interviews, the behavioral presentation of seizures, the history of
      traumatic experiences or abuse, and the relationship between PNES events and life
      stressors. Also, the Beck Depression Inventory-II was used to explore depressive
      symptoms. RESULTS: Seventy six percent (n = 26) of the patients were female, with
      an average age of 34.32. All the patients in this sample experienced a PNES
      episode that was induced in the office through hypnotic imagery. In most cases,
      seizures consistently manifested PNES semiology: 82% presented unsynchronized and
      violent limb movements and featured vocalizations, pronounced ictal pelvic
      thrusting, and sideto-side head movements. Furthermore, 47% of the patients
      reported histories of trauma related to sexual, physical or emotional abuse.
      Moreover, 94% stated that most of their convulsions were triggered by stressful
      life events. Additionally, 50% of the patients presented symptoms of depression.
      CONCLUSION: The clinical profile of patients with PNES reveals that a
      considerable number of them presented a history of multiple traumatic experiences
      and most seizures seemed to be induced by stressful events. It is recommended
      that additional clinical research be conducted on PNES, with the aim of achieving
      the effective detection and diagnosis of the disorder, as well as increasing the
      focus of the healthcare industry on developing evidence-based interventions.

PMID- 29220064
TI  - Importance of and Satisfaction with Psychosocial Support among Cancer Patients
      and Survivors in Puerto Rico: Gender, Health Status, and Quality of Life
      Associations.
AB  - OBJECTIVE: To assess needs perceptions regarding the importance of and
      satisfaction with psychosocial support among cancer patients and survivors in
      Puerto Rico. METHODS: A cross-sectional study was conducted in 181 participants
      (70 men and 111 women) who were either undergoing cancer treatment (patients) or
      had completed cancer treatment (survivors). Participants completed a
      sociodemographic and clinical characteristics questionnaire, and the Psychosocial
      Needs Inventory (PNI). RESULTS: The participants reported having or having had
      prostate (36%) or breast (32%) cancer or some other cancer type (32%). Of the 149
      participants reporting cancer type, 130 were classified as having a high
      perceived level of health and quality of life, and 19 were classified as having a
      low perceived level of health and quality of life. In terms of perceived needs,
      the highest level of importance were assigned to the Support Network (e.g.
      family, friends, neighbors, care professionals; M = 2.88, SD = 0.43) and Health
      Professional (e.g., patient-health professional relationship, etc.; M = 2.80, SD
      = 0.50) categories, and the Emotional and Spiritual category was given the lowest
      importance (e.g., help managing negative emotions and spiritual counseling, etc.;
      M = 2.62, SD = 0.66). These perceptions varied by gender, perceived health
      status, and date of diagnosis. Women assigned more importance to the Health
      Professional and Information categories. CONCLUSION: The results reflect the
      importance of considering psychosocial needs when providing psychosocial support
      to cancer patients and survivors. These findings are anticipated to inform
      services provided by psychosocial oncology support programs in Puerto Rico.

PMID- 29220066
TI  - Periorbital Changes associated with Topical Prostaglandins Analogues in a
      Hispanic Population.
AB  - OBJECTIVE: To describe the prevalent side effects of prostaglandin analogues (PA)
      in a Hispanic population and their effect on quality of life (QOL). PATIENTS AND
      METHODS: This is a cross-sectional study conducted in a tertiary medical facility
      in which patients were evaluated in a single visit. Total of 14 participants in
      the study, 10 women and 4 men. Ages ranged from 26-78 years old. Subjects
      underwent a single full Oculoplastic evaluation by two physicians; one was
      blinded on patient medical history and assessed for PA side effects. After
      evaluation, each study subject was asked to answer a self reported QOL
      questionnaire. RESULTS: Study participants had used or were currently using
      Bimatoprost (28.6%), Latanoprost (50%) or Travoprost (21.4%). After evaluate
      periorbital changes, 2 patients (14.3%) had ptosis, 2 (14.3%) had periorbital
      skin hyperpigmentation, 11 (78.6%) had periorbital fat show, 11 (78.6%) had
      eyelash elongation, 1 (7.1%) had injected conjunctiva, 5 (35.7%) had iris
      hyperpigmentation. 10 (71.4%) noted changes in the size/shape of their eyes. The
      questionnaire show that 10 (71.4%) disliked how their eyes looked. 9 (62.4%)
      reported dry eyes, 3 (21.4%) noted increased need to blink, 5 (35.7%) reported
      foreign body sensation, 7 (50%) reported burning sensation, 2 (14.2%) reported
      secretions and 3 (21.4%) reported sticky eyes. Mean QOL was 3.50, 2.14, and 2.00
      in the Bimatroprost, Latanoprost, and Travoprost users respectively. CONCLUSION:
      QOL questionnaire showed that Bimatoprost side effects had the most negative
      impact in QOL, followed by the Latanoprost and Travoprost groups.

PMID- 29220068
TI  - Assessing the Decrease in the Surgical Population of the University of Puerto
      Rico-Affiliated Hospitals.
AB  - OBJECTIVE: To evaluate the magnitude of the decrease in the surgical population
      of the University of Puerto Rico (UPR)-affiliated hospitals. METHODS: We examined
      all the surgical cases that were entered into the Surgical Database from January
      1, 2013, through December 31, 2015. This database collects patient and procedural
      information from the surgical services of the UPR-affiliated hospitals. Thus, the
      number of surgical patients for the 3-year study period was determined and their
      characteristics recorded. The group was subdivided into 3 subgroups, according to
      year: 2013, 2014, and 2015. All the variables studied were tabulated for the 3
      subgroups and the values compared. The differences between subgroups were
      evaluated using the chi2 test or ANOVA, whichever was appropriate, with a p-value
      of less than 0.05 being considered significant. RESULTS: During the 3-year
      period, the Surgical Database collected information on 14,626 cases. The mean age
      of the group was 48 (+/-23) years. The gender distribution indicated that 55% of
      the sample members were women and 45% were men. A 14% decline in the number of
      surgical cases occurred from 2013 through 2015. The changes were not limited to a
      decline in numbers; the patients were sicker, as evidenced by a statistically
      significant (p<0.05) increase in the number of patients who presented with an
      American Society of Anesthesiologist (ASA) physical status classification of 3 or
      higher. CONCLUSION: A moderately steady decline in the number of surgical cases
      at the UPR-affiliated hospitals was noted. We believe multiple factors are
      responsible for this trend, such as a decreasing population and the current
      economic and healthcare crises occurring in Puerto Rico.

PMID- 29220067
TI  - Gene Expression, and Fatigue in Puerto Rican Men during Radiotherapy for Prostate
      Cancer: an Exploratory Study.
AB  - OBJECTIVE: To examine the trajectory of fatigue experienced by 26 Puerto Rican
      (PR) men over the course of External Beam Radiation Therapy (EBRT) and to assess
      gene expression changes from baseline to midpoint of EBRT using microarray
      technology. Design/Research Approach- Prospective exploratory and comparative
      design study. Setting- RT facility located in San Juan, PR. Sample/Participants
      26 PR men with non-metastatic prostate cancer. METHODS: Participants completed 2
      paper forms: demographics and the Spanish version of the 13-item FACT-fatigue at
      baseline, midpoint, and end of EBRT. Wholeblood samples were collected at
      baseline and at midpoint of EBRT. Descriptive data was analyzed using t-test,
      Wilcoxon, and Friedman test for repeated measures. Gene expression data was
      analyzed using the LIMMA package in R; the functional network analysis was
      conducted using Ingenuity Pathway analysis. Main Research Variable-Fatigue
      scores, gene expression. RESULTS: Subjects were of ages 52-81 with fatigue scores
      that remained unchanged during EBRT (baseline=42.38, SD=9.34; midpoint=42.11,
      SD=8.93, endpoint=43.04, SD=8.62). Three hundred seventy-three genes (130-up
      regulated and 243-down regulated) were differentially expressed from baseline to
      mid-point of EBRT (FDR<0.01). The top distinct canonical pathways of the
      differentially expressed probesets (p<0.0001) were: "Phospholipase C Signaling,"
      "Role of NFAT in Regulation of the Immune Response," and "Galphaq Signaling."
      CONCLUSION: While fatigue did not worsen over the course of EBRT for this sample
      as a group, there was variability in fatigue across the sample. It is possible
      that the over expression of the SESN3 gene, known to suppress oxidative damage,
      may have contributed to the attenuation of fatigue in this clinical population.

PMID- 29220069
TI  - Traumatic Brain Injury Profile of an Elderly Population in Puerto Rico.
AB  - OBJECTIVE: Describe the types of traumatic brain injury secondary to falls
      sustained by the members of an elderly population who received services at the
      Puerto Rico Medical Center and the demographic profile of that population.
      METHODS: A group of 332 adults (60 years and over) assessed for traumatic brain
      injury secondary to falls suffered in 2013 were included in the analysis. The
      cases were retrieved from the computerized database of the Neurosurgery Section.
      We analyzed information such as age, gender, type of traumatic brain injury,
      mechanism of injury, and the performance of surgery (if applicable). Descriptive
      analysis was performed to derive a general profile of elderly adults who
      presented with traumatic brain injury secondary to falls. RESULTS: The sample
      consisted of 332 elderly adults: 73% were men and 27% were women. The mean age
      was 76.74 (SD=9.95) years: 75.67 (SD=9.78) for men and 79.13 (SD=10.02) for
      women. The most common traumatic brain injury was subdural hematoma (51%) and the
      mechanism of injury most prevalent was the groundlevel fall (83%). Other
      traumatic brain injuries included traumatic subarachnoid hemorrhages (14%),
      cerebral contusions (18%) and epidural hematomas (3%). Of all the cases, 52% had
      were managed surgically. CONCLUSION: The elderly population is growing and the
      risk of falls increases with advancing age. Recurrent falls are an important
      cause of morbidity, and mortality rates oscillate from 6 to 18%. Elderly patients
      have longer rehabilitation times, incur more expenses, and have greater levels of
      disability. This study provides a platform for future epidemiological studies to
      help develop strategies for the prevention of traumatic brain injury in older
      adults.

PMID- 29220070
TI  - Recurrent Hypokalemia leading to Flaccid Quadriparesis: A Renal or Connective
      Tissue Disorder.
AB  - Hypokalemic periodic paralysis (hypoKPP) is a clinical entity characterized by
      recurrent skeletal muscle paralysis due to a decrease in serum potassium levels;
      hypoKPP can have either a primary (familial) or a secondary cause. One of the
      secondary causes of hypoKPP is distal renal tubular acidosis (dRTA). Distal renal
      tubular acidosis (dRTA) is diagnosed when the urinary pH is greater than 5.3 and
      in the presence of hyperchloremic metabolic acidosis and hypokalemia, with one of
      the causes being primary Sjogren's syndrome (pSS). PSS can have both glandular
      and extra glandular manifestations, with dryness of the eyes and mouth being the
      most common presenting symptoms. DRTA arising from pSS is very unusual, occurring
      in fewer than 2% of the cases of Sjogren's syndrome (SS). Here, we report on a
      case of recurrent flaccid quadriparesis that appears to have been caused by
      distal RTA, resulting in hypokalemia; upon further investigation and clinical
      evaluation, the patient was diagnosed with pSS.

PMID- 29220071
TI  - Kommerell's Diverticulum in an Aberrant Right Subclavian Artery: First Case
      Reported in a Male of Puerto Rican Descent.
AB  - A Kommerell's diverticulum is a rare embryologic defect of the aortic arch. The
      majority of the patients having this defect present with dysphagia, dyspnea, and
      syncope, or a combination of any 2 or all 3. For symptomatic cases, surgical
      correction is always the standard of care. However, it is somewhat controversial
      what to do about asymptomatic cases. While surgery is almost always recommended,
      should asymptomatic patients undergo this procedure or not? Is it worth
      performing thoracic surgery for an anomaly whose nature is not really understood?
      In this case report, we describe a Kommerell diverticulum discovered incidentally
      in a 70-year old asymptomatic male. Surgery was not advisable for this patient;
      therefore, it was decided to manage him with surveillance. This is the first
      report in the Englishlanguage medical literature of a Kommerell diverticulum in a
      man of Puerto Rican descent. A thorough discussion of this rare anomaly follows;
      multimodality images of it are included at the end of this manuscript.

PMID- 29220073
TI  - Collective effects of common single nucleotide polymorphisms and genetic risk
      prediction in type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a common autoimmune disease and may be related to
      multiple genetic and environmental risk factors. Previous genetic studies have
      focused on looking for individual polymorphic risk variants. Here, we studied the
      overall levels of genetic diversity in T1D patients by making use of a previously
      published study including 1865 cases and 2828 reference samples with genotyping
      data for 500 K common single nucleotide polymorphisms (SNPs). We determined the
      minor allele (MA) status of each SNP in the reference samples and calculated the
      total number of MAs or minor allele contents (MAC) of each individual. We found
      the average MAC of cases to be greater than that of the reference samples. By
      focusing on MAs with strong linkage to cases, we further identified a set of 112
      SNPs that could predict 19.19% of cases. These results suggest that overall
      genetic variation over a threshold level may be a risk factor in T1D and provide
      a new genetic method for predicting the disorder.

PMID- 29220072
TI  - Falls Predict Fractures Independently of FRAX Probability: A Meta-Analysis of the
      Osteoporotic Fractures in Men (MrOS) Study.
AB  - Although prior falls are a well-established predictor of future fracture, there
      is currently limited evidence regarding the specific value of falls history in
      fracture risk assessment relative to that of other clinical risk factors and bone
      mineral density (BMD) measurement. We therefore investigated, across the three
      Osteoporotic Fractures in Men (MrOS) Study cohorts, whether past falls predicted
      future fracture independently of FRAX and whether these associations varied with
      age and follow-up time. Elderly men were recruited from MrOS Sweden, Hong Kong,
      and USA. Baseline data included falls history (over the preceding 12 months),
      clinical risk factors, BMD at femoral neck, and calculated FRAX probabilities. An
      extension of Poisson regression was used to investigate the associations between
      falls, FRAX probability, and incident fracture, adjusting for age, time since
      baseline, and cohort in base models; further models were used to investigate
      interactions with age and follow-up time. Random-effects meta-analysis was used
      to synthesize the individual country associations. Information on falls and FRAX
      probability was available for 4365 men in USA (mean age 73.5 years; mean follow
      up 10.8 years), 1823 men in Sweden (mean age 75.4 years; mean follow-up 8.7
      years), and 1669 men in Hong Kong (mean age 72.4 years; mean follow-up 9.8
      years). Rates of past falls were similar at 20%, 16%, and 15%, respectively.
      Across all cohorts, past falls predicted incident fracture at any site (hazard
      ratio [HR] = 1.69; 95% confidence interval [CI] 1.49, 1.90), major osteoporotic
      fracture (MOF) (HR = 1.56; 95% CI 1.33, 1.83), and hip fracture (HR = 1.61; 95%
      CI 1.27, 2.05). Relationships between past falls and incident fracture remained
      robust after adjustment for FRAX probability: adjusted HR (95% CI) any fracture:
      1.63 (1.45, 1.83); MOF: 1.51 (1.32, 1.73); and hip: 1.54 (1.21, 1.95). In
      conclusion, past falls predicted incident fracture independently of FRAX
      probability, confirming the potential value of falls history in fracture risk
      assessment. (c) 2017 The Authors. Journal of Bone and Mineral Research Published
      by Wiley Periodicals Inc.

PMID- 29220074
TI  - Prediction of Protein-Protein Interactions.
AB  - The authors provide an overview of physical protein-protein interaction
      prediction, covering the main strategies for predicting interactions, approaches
      for assessing predictions, and online resources for accessing predictions. This
      unit focuses on the main advancements in each of these areas over the last
      decade. The methods and resources that are presented here are not an exhaustive
      set, but characterize the current state of the field-highlighting key challenges
      and achievements. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29220075
TI  - Protein 3D Structure and Electron Microscopy Map Retrieval Using 3D-SURFER2.0 and
      EM-SURFER.
AB  - With the rapid growth in the number of solved protein structures stored in the
      Protein Data Bank (PDB) and the Electron Microscopy Data Bank (EMDB), it is
      essential to develop tools to perform real-time structure similarity searches
      against the entire structure database. Since conventional structure alignment
      methods need to sample different orientations of proteins in the three
      dimensional space, they are time consuming and unsuitable for rapid, real-time
      database searches. To this end, we have developed 3D-SURFER and EM-SURFER, which
      utilize 3D Zernike descriptors (3DZD) to conduct high-throughput protein
      structure comparison, visualization, and analysis. Taking an atomic structure or
      an electron microscopy map of a protein or a protein complex as input, the 3DZD
      of a query protein is computed and compared with the 3DZD of all other proteins
      in PDB or EMDB. In addition, local geometrical characteristics of a query protein
      can be analyzed using VisGrid and LIGSITECSC in 3D-SURFER. This article describes
      how to use 3D-SURFER and EM-SURFER to carry out protein surface shape similarity
      searches, local geometric feature analysis, and interpretation of the search
      results. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29220076
TI  - The HMMER Web Server for Protein Sequence Similarity Search.
AB  - Protein sequence similarity search is one of the most commonly used
      bioinformatics methods for identifying evolutionarily related proteins. In
      general, sequences that are evolutionarily related share some degree of
      similarity, and sequence-search algorithms use this principle to identify
      homologs. The requirement for a fast and sensitive sequence search method led to
      the development of the HMMER software, which in the latest version (v3.1) uses a
      combination of sophisticated acceleration heuristics and mathematical and
      computational optimizations to enable the use of profile hidden Markov models
      (HMMs) for sequence analysis. The HMMER Web server provides a common platform by
      linking the HMMER algorithms to databases, thereby enabling the search for
      homologs, as well as providing sequence and functional annotation by linking
      external databases. This unit describes three basic protocols and two alternate
      protocols that explain how to use the HMMER Web server using various input
      formats and user defined parameters. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29220077
TI  - Using the Arabidopsis Information Resource (TAIR) to Find Information About
      Arabidopsis Genes.
AB  - The Arabidopsis Information Resource (TAIR; http://arabidopsis.org) is a
      comprehensive Web resource of Arabidopsis biology for plant scientists. TAIR
      curates and integrates information about genes, proteins, gene function,
      orthologs, gene expression, mutant phenotypes, biological materials such as
      clones and seed stocks, genetic markers, genetic and physical maps, genome
      organization, images of mutant plants, protein sub-cellular localizations,
      publications, and the research community. The various data types are extensively
      interconnected and can be accessed through a variety of Web-based search and
      display tools. This unit primarily focuses on some basic methods for searching,
      browsing, visualizing, and analyzing information about Arabidopsis genes and
      genome. Additionally, we describe how members of the community can share data
      using TAIR's Online Annotation Submission Tool (TOAST), in order to make their
      published research more accessible and visible. (c) 2017 by John Wiley & Sons,
      Inc.

PMID- 29220078
TI  - Using the Seven Bridges Cancer Genomics Cloud to Access and Analyze Petabytes of
      Cancer Data.
AB  - Next-generation sequencing has produced petabytes of data, but accessing and
      analyzing these data remain challenging. Traditionally, researchers investigating
      public datasets like The Cancer Genome Atlas (TCGA) would download the data to a
      high-performance cluster, which could take several weeks even with a highly
      optimized network connection. The National Cancer Institute (NCI) initiated the
      Cancer Genomics Cloud Pilots program to provide researchers with the resources to
      process data with cloud computational resources. We present protocols using one
      of these Cloud Pilots, the Seven Bridges Cancer Genomics Cloud (CGC), to find and
      query public datasets, bring your own data to the CGC, analyze data using
      standard or custom workflows, and benchmark tools for accuracy with interactive
      analysis features. These protocols demonstrate that the CGC is a data-analysis
      ecosystem that fully empowers researchers with a variety of areas of expertise
      and interests to collaborate in the analysis of petabytes of data. (c) 2017 by
      John Wiley & Sons, Inc.

PMID- 29220079
TI  - Hepatitis C virus genotyping of organ donor samples to aid in transplantation of
      HCV-positive organs.
AB  - Given the availability of new highly efficacious anti-HCV therapies, some
      clinicians have advocated for wider use of kidneys from hepatitis C virus
      positive (HCV+) donors, including transplanting them into HCV-negative
      recipients. As treatment regimens for HCV are commonly guided by genotype,
      pretransplant HCV genotyping of tissue donors would be beneficial. To our
      knowledge, donor HCV genotyping has never been reported. We retrieved archived
      frozen plasma samples for 17 previous organ donors through a local organ
      procurement organization. We performed HCV genotyping using the eSensor HCVg
      Direct Test (GenMark Diagnostics) and also by Sanger sequencing, for confirmation
      (Retrogen). In addition, viral loads were measured using the COBAS
      AmpliPrep/TaqMan system (Roche Diagnostics). We found that most of the samples (n
      = 14) were HCV Genotype 1a with the remainder being Genotype 2b (n = 1) or
      Genotype 3 (n = 2). All genotyping results were concordant with Sanger
      sequencing. The average HCV viral load in the sample group was ~ 1.6 million
      IU/mL (range: ~16 000 IU/mL to 7 million IU/mL). We demonstrate that viral RNA
      from organ donor plasma can be successfully genotyped for HCV. This ability
      suggests that transplantation of HCV+ kidneys into HCV-negative recipients,
      followed by genotype-guided antiviral therapy, could be feasible.

PMID- 29220080
TI  - High salinity impacts germination of the halophyte Cakile maritima but primes
      seeds for rapid germination upon stress release.
AB  - Seed germination recovery aptitude is an adaptive trait of overriding
      significance for the successful establishment and dispersal of extremophile
      plants in their native ecosystems. Cakile maritima is an annual halophyte
      frequent on Mediterranean coasts, which produces transiently dormant seeds under
      high salinity, that germinate fast when soil salinity is lowered by rainfall.
      Here, we report ecophysiological and proteomic data about (1) the effect of high
      salt (200 mM NaCl) on the early developmental stages (germination and seedling)
      and (2) the seed germination recovery capacity of this species. Upon salt
      exposure, seed germination was severely inhibited and delayed and seedling length
      was restricted. Interestingly, non-germinated seeds remained viable, showing high
      germination percentage and faster germination than the control seeds after their
      transfer onto distilled water. The plant phenotypic plasticity during germination
      was better highlighted by the proteomic data. Salt exposure triggered (1) a
      marked slower degradation of seed storage reserves and (2) a significant lower
      abundance of proteins involved in several biological processes (primary
      metabolism, energy, stress-response, folding and stability). Yet, these proteins
      showed strong increased abundance early after stress release, thereby sustaining
      the faster seed storage proteins mobilization under recovery conditions compared
      to the control. Overall, as part of the plant survival strategy, C. maritima
      seems to avoid germination and establishment under high salinity. However, this
      harsh condition may have a priming-like effect, boosting seed germination and
      vigor under post-stress conditions, sustained by active metabolic machinery.

PMID- 29220081
TI  - Comment on "Longitudinal transvaginal ultrasound evaluation of cesarean scar
      niche incidence and depth in the first two years after single- or double-layer
      uterotomy closure: a randomized controlled trial".

PMID- 29220082
TI  - Benefits of multimodal enhanced recovery pathway in patients undergoing kidney
      transplantation.
AB  - BACKGROUND: Use of enhanced recovery after surgery (ERAS) pathways to accelerate
      functional recovery and reduce length of stay (LOS) has rarely been investigated
      in kidney transplantation (KTX). MATERIALS AND METHODS: Consecutive adult
      isolated KTXs between July 2015 and July 2016 (ERAS, n = 139) were compared with
      a historical cohort between January 2014 and July 2015 (HISTORIC, n = 95).
      RESULTS: Enhanced recovery after surgery recipients were significantly more
      likely to receive kidneys that were non-local (56.1% vs 4.2%), higher Kidney
      Donor Profile Index (36-85, 58.4% vs 45.2%; >85, 15.2% vs 10.7%), cold ischemia
      time >=30 h (62.4% vs 4.7%), induced with antithymocyte globulin (97.1% vs
      87.4%), and to develop delayed graft function (46.4% vs 25.0%). LOS was shorter
      by 1 day among ERAS (mean 4.59) compared to HISTORIC patients (mean 5.65)
      predominantly due to a shift in discharges within 3 days (32.4% vs 4.2%); 30-day
      readmission to the hospital (27.3% vs 27.4%) or emergency room visit (9.4% vs
      7.4%) was similar. There was one 30-day death in the ERAS group and none in the
      HISTORIC group. Return to bowel function and early meal consumption were
      significantly associated with ERAS, however, with somewhat higher diarrhea and
      emesis rates. CONCLUSION: ERAS following KTX correlated with lower LOS without
      change in readmissions or ER visits despite higher delayed graft function rates.

PMID- 29220085
TI  - Managing Large, Transdisciplinary Projects.

PMID- 29220086
TI  - Zinc against advanced glycation end products.
AB  - Advanced glycation end products (AGEs) are destructive compounds with pathogenic
      importance in age-related chronic diseases. Zinc has antioxidant, anti
      inflammatory and anti-apoptotic potential. This study aimed to summarize effects
      of zinc on AGE formation and AGE-induced damaging agents. Pubmed, Google scholar,
      Web of Sciences, and Scopus databases were searched. There was no limitation for
      publication date. English language original articles (in vitro, experimental and
      human studies) which examined the effect of external zinc on AGE formation, AGE
      induced apoptosis, or oxidative stress in mammals were included. To review the
      effect of zinc on AGE generation, the search keywords were as follows: "zinc" in
      title and "AGEs" or "methylglyoxal" or "pentosidine" or "carboxymethyllysine" or
      "glucosylation" or "carbonyl stress" or "AGEs-induced apoptosis or oxidative
      stress or inflammation" in title/abstract. In total, 90 titles and abstracts were
      identified. Fifty-two studies were screened after duplicates were removed. Six
      articles were chosen for review following analysis of both titles and summaries.
      Finally, based on intensive critical appraisal, 5 articles were included in the
      study. The evidence presented indicates that zinc has anti-glycation, anti
      oxidative and anti-apoptotic effects. Zinc insufficiency may stimulate AGEs
      formation. Whereas, zinc supplementation could inhibit formation of AGEs, AGE
      induced cell apoptosis and oxidative stress status, and protein carbonyl
      formation possibly through various signalling pathways.

PMID- 29220087
TI  - Dual-energy-based metal segmentation for metal artifact reduction in dental
      computed tomography.
AB  - PURPOSE: In a dental CT scan, the presence of dental fillings or dental implants
      generates severe metal artifacts that often compromise readability of the CT
      images. Many metal artifact reduction (MAR) techniques have been introduced, but
      dental CT scans still suffer from severe metal artifacts particularly when
      multiple dental fillings or implants exist around the region of interest. The
      high attenuation coefficient of teeth often causes erroneous metal segmentation,
      compromising the MAR performance. We propose a metal segmentation method for a
      dental CT that is based on dual-energy imaging with a narrow energy gap. METHODS:
      Unlike a conventional dual-energy CT, we acquire two projection data sets at two
      close tube voltages (80 and 90 kVp ), and then, we compute the difference image
      between the two projection images with an optimized weighting factor so as to
      maximize the contrast of the metal regions. We reconstruct CT images from the
      weighted difference image to identify the metal region with global thresholding.
      We forward project the identified metal region to designate metal trace on the
      projection image. We substitute the pixel values on the metal trace with the ones
      computed by the region filling method. The region filling in the metal trace
      removes high-intensity data made by the metallic objects from the projection
      image. We reconstruct final CT images from the region-filled projection image
      with the fusion-based approach. We have done imaging experiments on a dental
      phantom and a human skull phantom using a lab-built micro-CT and a commercial
      dental CT system. RESULTS: We have corrected the projection images of a dental
      phantom and a human skull phantom using the single-energy and dual-energy-based
      metal segmentation methods. The single-energy-based method often failed in
      correcting the metal artifacts on the slices on which tooth enamel exists. The
      dual-energy-based method showed better MAR performances in all cases regardless
      of the presence of tooth enamel on the slice of interest. We have compared the
      MAR performances between both methods in terms of the relative error (REL), the
      sum of squared difference (SSD) and the normalized absolute difference (NAD). For
      the dental phantom images corrected by the single-energy-based method, the metric
      values were 95.3%, 94.5%, and 90.6%, respectively, while they were 90.1%, 90.05%,
      and 86.4%, respectively, for the images corrected by the dual-energy-based
      method. For the human skull phantom images, the metric values were improved from
      95.6%, 91.5%, and 89.6%, respectively, to 88.2%, 82.5%, and 81.3%, respectively.
      CONCLUSIONS: The proposed dual-energy-based method has shown better performance
      in metal segmentation leading to better MAR performance in dental imaging. We
      expect the proposed metal segmentation method can be used to improve the MAR
      performance of existing MAR techniques that have metal segmentation steps in
      their correction procedures.

PMID- 29220088
TI  - Multi-walled carbon nanotubes applied through seed-priming influence early
      germination, root hair, growth and yield of bread wheat (Triticum aestivum L.).
AB  - BACKGROUND: Reports of multi-walled carbon nanotubes (MWCNTs) incorporated into
      plants have indicated better yield and productivity, yet the phenomena need in
      depth understanding especially when agricultural crops are tested. We primed
      wheat seeds with MWCNTs to understand the effects on germination, growth,
      anatomy, physiology and yield. RESULT: This study, carried out in field
      conditions, is a step forward over the previous reports. Early germination,
      excessive root hair, denser stomata and larger root length result in faster
      growth and higher yield of wheat plants. Denser root hair facilitated the uptake
      of both water and essential minerals such as phosphorus (P) and potassium (K),
      which boosted the crop yield by significantly improving grain yield per plant
      from 1.53 to 2.5 g, a 63% increase. Increase in cell elongation by 80% was
      recorded, while xylem and phloem sizes dilated to almost 83% and 85% of control,
      thus enhancing their capacity to conduct water and nutrients. CONCLUSION:
      Augmented growth of MWCNT-primed wheat, enhancement in grain number, biomass,
      stomatal density, xylem-phloem size, epidermal cells, and water uptake is
      observed while finding no DNA damage. This opens up an entirely new aspect to
      using cost-effective nanomaterials (the MWCNTs were produced in-house) for
      enhancing the performance of crop plants. (c) 2017 Society of Chemical Industry.

PMID- 29220089
TI  - Potato plants (Solanum tuberosum L.) are chloride-sensitive: Is this dogma valid?
AB  - BACKGROUND: Chloride sensitivity of the potato (Solanum tuberosum L.) cultivars
      Marabel and Desiree was investigated in two pot experiments (soil/sand mixture
      and hydroponics). It was tested whether there are differential effects of KCl and
      K2 SO4 application on tuber yield and tuber quality, and whether both potato
      cultivars differ in their chloride sensitivity. RESULTS: Tuber yield, dry matter
      percentage of the tubers, starch concentration and starch yield were not
      significantly affected by potassium source (K2 SO4 or KCl). After exposure to
      salt stress in hydroponics (100 mmol L-1 NaCl, 50 mmol L-1 Na2 SO4 , 50 mmol L-1
      CaCl2 ) for 5 days, 3-week-old potato plants had significantly reduced shoot dry
      mass after NaCl and Na2 SO4 application. However, CaCl2 treatment did not
      significantly affect shoot growth, although the chloride concentration reached 65
      to 74 mg Cl- mg-1 dry matter, similar to the NaCl treatment. In contrast, growth
      reductions were closely related to sodium concentrations, thus plants suffered
      sodium toxicity and not chloride toxicity. CONCLUSION: Both potato cultivars are
      chloride-resistant and can be fertilised with KCl instead of K2 SO4 without the
      risk of depression in tuber yield or tuber quality. The statement that potatoes
      are chloride-sensitive and that chloride has negative effects on yield
      performance needs reconsideration. (c) 2017 Society of Chemical Industry.

PMID- 29220090
TI  - Mesophyll conductance in Zea mays responds transiently to CO2 availability:
      implications for transpiration efficiency in C4 crops.
AB  - Mesophyll conductance (gm ) describes the movement of CO2 from the intercellular
      air spaces below the stomata to the site of initial carboxylation in the
      mesophyll. In contrast with C3 -gm , little is currently known about the
      intraspecific variation in C4 -gm or its responsiveness to environmental stimuli.
      To address these questions, gm was measured on five maize (Zea mays) lines in
      response to CO2 , employing three different estimates of gm . Each of the methods
      indicated a significant response of gm to CO2 . Estimates of gm were similar
      between methods at ambient and higher CO2 , but diverged significantly at low
      partial pressures of CO2 . These differences are probably driven by incomplete
      chemical and isotopic equilibrium between CO2 and bicarbonate under these
      conditions. Carbonic anhydrase and phosphoenolpyruvate carboxylase in vitro
      activity varied significantly despite similar values of gm and leaf anatomical
      traits. These results provide strong support for a CO2 response of gm in Z. mays,
      and indicate that gm in maize is probably driven by anatomical constraints rather
      than by biochemical limitations. The CO2 response of gm indicates a potential
      role for facilitated diffusion in C4 -gm . These results also suggest that water
      use efficiency could be enhanced in C4 species by targeting gm .

PMID- 29220091
TI  - John Walker-Smith: the father of European paediatric gastroenterology.

PMID- 29220092
TI  - Dose rectification of an imbalance between DPP4 and GLP-1 ameliorates chronic
      stress-related vascular aging and atherosclerosis?
AB  - Exposure to psychosocial stress is a risk factor for cardiovascular disease,
      including vascular aging and regeneration. Dipeptidyl peptidase-4 (DPP-4) exerts
      many physiological and pharmacological functions by regulating its extremely
      abundant substrates [eg., glucagon-like peptide-1 (GLP-1), stromal cell-derived
      factor-1alpha/C-X-C chemokine receptor type-4, etc.]. Over the past decade,
      emerging data has revealed unexpected roles for DPP-4 and GLP-1 in intracellular
      signaling, oxidative stress production, lipid metabolism, cell apoptosis, immune
      activation, insulin resistance, and inflammation. This mini review focuses on
      recent findings in this field, highlighting an imbalance between DPP4 and GLP-1
      as a potential therapeutic target in the management of vascular aging and
      atherosclerosis in animals under experimental stress conditions.

PMID- 29220093
TI  - Separate product from process: framing the debate that surrounds the potential
      uptake of new breeding technologies.

PMID- 29220095
TI  - Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and
      mitotic counts in breast cancer.
AB  - AIMS: During pathological examination of breast tumours, proliferative activity
      is routinely evaluated by a count of mitoses. Adding immunohistochemical stains
      of Ki67 provides extra prognostic and predictive information. However, the
      currently used methods for these evaluations suffer from imperfect
      reproducibility. It is still unclear whether analysis of Ki67 should be performed
      in hot spots, in the tumour periphery, or as an average of the whole tumour
      section. The aim of this study was to compare the clinical relevance of mitoses,
      Ki67 and phosphohistone H3 in two cohorts of primary breast cancer specimens
      (total n = 294). METHODS AND RESULTS: Both manual and digital image analysis
      scores were evaluated for sensitivity and specificity for luminal B versus A
      subtype as defined by PAM50 gene expression assays, for high versus low
      transcriptomic grade, for axillary lymph node status, and for prognostic value in
      terms of prediction of overall and relapse-free survival. Digital image analysis
      of Ki67 outperformed the other markers, especially in hot spots. Tumours with
      high Ki67 expression and high numbers of phosphohistone H3-positive cells had
      significantly increased hazard ratios for all-cause mortality within 10 years
      from diagnosis. Replacing manual mitotic counts with digital image analysis of
      Ki67 in hot spots increased the differences in overall survival between the
      highest and lowest histological grades, and added significant prognostic
      information. CONCLUSIONS: Digital image analysis of Ki67 in hot spots is the
      marker of choice for routine analysis of proliferation in breast cancer.

PMID- 29220094
TI  - Osteocytes play an important role in experimental periodontitis in healthy and
      diabetic mice through expression of RANKL.
AB  - AIM: Periodontitis results from bacteria-induced inflammation. A key cytokine,
      RANKL, is produced by a number of cell types. The cellular source of RANKL
      critical for periodontitis has not been established. METHODS: We induced
      periodontal bone loss by oral inoculation of Porphyromonas gingivalis and
      Fusobacterium nucleatum in both normoglycaemic and streptozotocin-induced type 1
      diabetic mice. Experimental transgenic mice had osteocyte-specific deletion of
      floxed receptor activator of nuclear factor kappa-B ligand (RANKL) mediated by
      DMP-1-driven Cre recombinase. Outcomes were assessed by micro-CT,
      histomorphometric analysis, immunofluorescent analysis of RANKL and tartrate
      resistant acid phosphatase staining for osteoclasts and osteoclast activity.
      RESULTS: Oral infection stimulated RANKL expression in osteocytes of wild-type
      mice, which was increased by diabetes and blocked in transgenic mice. Infected
      wild-type mice had significant bone loss and increased osteoclast numbers and
      activity, which were further enhanced by diabetes. No bone loss or increase in
      osteoclastogenesis or activity was detected in transgenic mice with RANKL
      deletion in osteocytes that were normoglycaemic or diabetic. CONCLUSIONS: This
      study demonstrates for the first time the essential role of osteocytes in
      bacteria-induced periodontal bone loss and in diabetes-enhanced periodontitis.

PMID- 29220096
TI  - Hepatic progenitor cells in metastatic liver carcinomas.
AB  - AIMS: Hepatic progenitor cells (HPCs) are activated in various liver diseases,
      but their role in the carcinomatous environment remains unknown. We aimed to
      identify the possible presence and topography of HPCs in liver metastases.
      METHODS AND RESULTS: We examined 14 liver resection specimens for colorectal
      adenocarcinoma (n = 13) and anal squamous cell carcinoma (n = 1) metastases.
      Immunohistochemical markers of colonic origin (keratin 20 and CDX2) and squamous
      cell origin (p63), HPC [keratin 19 (K19) and CD56] and stem cell (CD44) markers,
      and the biliary marker keratin 7 (K7), which may also highlight HPCs, were
      applied on routinely processed tissue sections. Double
      immunohistochemistry/immunofluorescence (K7/CDX2) and confocal microscopy were
      used on selected sections. K7-positive, Kappa19-positive and CD56-positive
      ductular structures were encountered within the metastatic tumour (tumour
      interior and periphery), and in the immediate peritumoral area. Hybrid structures
      composed of HPCs and metastatic adenocarcinoma cells were recognised and
      confirmed by double immunostaining (K7/CDX2). Carcinoma cells were also observed
      singly or in groups within the epithelium of interlobular bile ducts and/or
      ductules in portal tracts without evidence of carcinomatous infiltration and at a
      distance from the metastatic foci. CONCLUSIONS: HPCs are observed at the
      periphery and in the interior of liver metastatic carcinomas. Bile ductules and
      small interlobular bile ducts may attract carcinoma cells serving as a potential
      'metastatic niche', in line with their recognised role as HPC niches in non
      neoplastic liver.

PMID- 29220098
TI  - Trace analysis in water-alcohol mixtures by continuous p-H2 hyperpolarization at
      high magnetic field.
AB  - Nuclear magnetic resonance (NMR) studies of complex mixtures are often limited by
      the low sensitivity of the technique and by spectral overlap. We have recently
      reported on an NMR chemosensor on the basis of para-Hydrogen Induced Polarization
      that potentially addresses both these issues, albeit for specific classes of
      compounds. This approach makes use of Signal Amplification By Reversible Exchange
      (SABRE) catalysts in methanol and allows selective detection and quantification
      of dilute analytes in complex mixtures. Herein, we demonstrate that, despite a
      large decrease in attained hyperpolarization, this method can be extended to
      water-alcohol mixtures. Our approach was tested on whisky, where nitrogenous
      heterocyclic flavor components at low-micromolar concentration could be detected
      and quantified.

PMID- 29220097
TI  - Invasive mucinous carcinoma of the breast and response patterns after neoadjuvant
      chemotherapy (NAC).
AB  - AIMS: Neoadjuvant chemotherapy (NAC) is often used to treat localised invasive
      breast cancer. Invasive mucinous carcinoma (IMC) is considered to be an indolent
      form of invasive breast cancer, and is rarely treated with NAC. We report the
      largest series of IMCs treated with NAC, and report a characteristic, but not
      well recognised, pattern of pathological response. METHODS AND RESULTS: Our
      series included seven patients with IMC treated with NAC. Three patients
      presented with locally advanced disease, three patients had tumours that were HER
      2/neu-positive, and four patients had tumours with admixed mucinous and
      micropapillary features. Clinical and imaging assessment of response showed
      persistent and, in some cases, progressive disease, despite evidence of
      significant pathological response in these cases. Pathological assessment after
      NAC demonstrated marked reduction in tumour cellularity, but persistent space
      occupying mucin pools, showing acellular mucin in one case, <1% tumour
      cellularity in three cases, and 5-10% cellularity in three cases in both the
      treated breast and axillary lymph nodes. CONCLUSIONS: Persistent mass-forming low
      cellular or acellular mucin pools can result in discordant clinical, imaging and
      pathological findings in IMC treated with NAC.

PMID- 29220099
TI  - Supportive palliative care should be integrated into routine care for paediatric
      patients with life-limiting kidney disease.
AB  - : Paediatric palliative care is no longer restricted to patients with cancer and
      has been extended to patients with other chronic conditions, such as cystic
      fibrosis or neuromuscular disorders. This review focused on the current state of
      palliative care for children and adolescents with chronic kidney disease (CKD).
      We assessed the literature on CKD published up to August 2017. All the papers,
      except one from 1996, were published this century. This review discusses the role
      that palliative care plays in the process of decision-making and explores the
      possibilities of implementing palliative care into the routine therapy of
      affected patients and providing support for their families. Offering early
      palliative care as an integral part of the kidney, supportive care provided by
      the nephrology care team is both necessary and feasible for patients with CKD. As
      a minimum, a specialised palliative care team should be involved in patients with
      multiple comorbidities, in conservative treatment scenarios and in acute life
      threatening complications. Further studies and guidelines are required to improve
      the care of patients with CKD and their families. CONCLUSION: Supportive
      palliative care should be implemented into the routine care of patients with life
      limiting kidney disease.

PMID- 29220101
TI  - Report of AAPM Task Group 162: Software for planar image quality metrology.
AB  - PURPOSE: The AAPM Task Group 162 aimed to provide a standardized approach for the
      assessment of image quality in planar imaging systems. This report offers a
      description of the approach as well as the details of the resultant software
      bundle to measure detective quantum efficiency (DQE) as well as its basis
      components and derivatives. METHODS: The methodology and the associated software
      include the characterization of the noise power spectrum (NPS) from planar images
      acquired under specific acquisition conditions, modulation transfer function
      (MTF) using an edge test object, the DQE, and effective DQE (eDQE). First, a
      methodological framework is provided to highlight the theoretical basis of the
      work. Then, a step-by-step guide is included to assist in proper execution of
      each component of the code. Lastly, an evaluation of the method is included to
      validate its accuracy against model-based and experimental data. RESULTS: The
      code was built using a Macintosh OSX operating system. The software package
      contains all the source codes to permit an experienced user to build the suite on
      a Linux or other *nix type system. The package further includes manuals and
      sample images and scripts to demonstrate use of the software for new users. The
      results of the code are in close alignment with theoretical expectations and
      published results of experimental data. CONCLUSIONS: The methodology and the
      software package offered in AAPM TG162 can be used as baseline for
      characterization of inherent image quality attributes of planar imaging systems.

PMID- 29220102
TI  - Identification of a 62-kDa major allergen from Artemisia pollen as a putative
      galactose oxidase.
AB  - BACKGROUND: Around 20 years ago, a 60- to 70-kDa protein was reported as a major
      allergen of mugwort (Artemisia vulgaris) pollen. This study was to identify and
      characterize its molecular properties. METHODS: Sera from 113 Chinese and 20
      Dutch Artemisia-allergic/sensitized subjects (and pools thereof) were used to
      identify the 60- to 70-kDa allergen. Pollen extracts of seven Artemisia species
      were compared by immunoblotting. Transcriptomics and proteomics (mass
      spectrometry) of A. annua pollen were used to identify the putative 60- to 70-kDa
      Artemisia allergen. Both the natural purified and recombinant allergens were
      evaluated for IgE reactivity by ImmunoCAP. Fourteen Chinese Artemisia-allergic
      patients were tested intradermally with purified natural allergen. RESULTS:
      Immunoblots revealed two major bands at 12 and 25 kDa, and a weak band at 70 kDa
      for all seven Artemisia species. Using a combined transcriptomic and proteomic
      approach, the high molecular mass allergen in A. annua pollen was shown to be a
      62-kDa putative galactose oxidase, with a putative N-glycosylation site. More
      than 94% of Artemisia pollen-allergic patients had IgE response to this allergen.
      Although recognition of a nonglycosylated recombinant version was only confirmed
      in a minority (16%) and at much lower IgE levels, this discrepancy cannot be
      explained simply by reactivity to the carbohydrate moiety on the natural
      allergen. Intradermal testing with the natural allergen was positive in five of
      nine sensitized patients. CONCLUSIONS: The previously reported 60- to 70-kDa
      allergen of Artemisia pollen is most likely a 62-kDa putative galactose oxidase
      here designated Art an 7.

PMID- 29220103
TI  - Survival study of treatment adherence by patients given oral oxibutynin for
      hyperhidrosis.
AB  - INTRODUCTION: In recent years, increasing use has been made of oral
      anticholinergics such as oxybutynin for the management of hyperhidrosis. The
      primary aim of this study is to determine the variables associated with adherence
      to this treatment, and secondarily to obtain data on its effectiveness, safety
      and adverse effects. MATERIAL AND METHODS: This is a prospective study of
      patients with hyperhidrosis, at any location, receiving treatment with oral
      oxybutynin in the period 2007-2016. Epidemiological variables, treatment details,
      effectiveness and adverse effects were recorded. Effectiveness was determined
      according to the Hyperhidrosis Disease Severity Scale (HDSS) at baseline, at 3
      and 12 months and in successive visits. A descriptive analysis was performed, and
      Cox's bivariate and multivariate regressions were calculated to determine the
      variables associated with treatment adherence. RESULTS: A total of 201 patients
      (140 women) with a mean age of 34 years were included. The mean initial HDSS
      score was 3.8, and the median follow-up period was 29 months. At 3 months, 84.57%
      of the patients had responded to treatment (excellent response: 72.94%), but
      adverse effects were reported by 68.2%. At 12 months, 54.23% had responded
      (excellent response: 79.82%), with adverse effects in 75.2%. The main variable
      associated with greater adherence was affected areas: palms of the hands and
      soles of the feet. The following variables were associated with poorer adherence:
      onset of hyperhidrosis in adolescence, failure to provide an incrementally
      increasing, individualized dose, initial HDSS score of 3 and partial initial
      response. The multivariate analysis confirmed the association between the onset
      of hyperhidrosis during adolescence, the failure to provide a progressively
      increasing dose and palmar affectation. DISCUSSION: This study was conducted to
      identify the variables associated with adherence to treatment by hyperhidrosis
      patients treated with oral oxybutynin. This information would facilitate
      selection of patients for this treatment and enhance our understanding of the
      biological behaviour of such anticholinergics when used to treat hyperhidrosis.

PMID- 29220104
TI  - Pitfalls in graft survival analysis.
AB  - The reliability of a scientific work depends on the accuracy of the analysis.
      Scientific publications in the field of kidney transplantation still contain
      methodical errors that may lead to wrong conclusions and result in severe
      consequences for the patients. Using the data from the Collaborative Transplant
      Study, we are presenting in this study six examples of the erroneous usage of
      statistical methods and show how these mistakes can be avoided.

PMID- 29220107
TI  - Eating out with a food allergy in the UK: Change in the eating out practices of
      consumers with food allergy following introduction of allergen information
      legislation.
AB  - BACKGROUND: Strict allergen avoidance is important in day-to-day management of
      food allergy and avoidance when eating outside the home can present particular
      difficulties. EU legislation (EU FIC) introduced in December 2014 aimed to
      improve food allergen information provision for customers by requiring retailers
      of non-prepacked foods to provide information related to the content of one or
      more of 14 specified food allergens within their foods. OBJECTIVES: To
      investigate the impact of EU FIC on the behaviours, experiences and attitudes of
      consumers with food allergy when eating out. METHODS: As part of longitudinal
      research, participants with food allergy from across the UK took part in either
      (A) pre and post legislation in-depth interviews, or (B) pre and post legislation
      surveys. In-depth interviews were carried out with 28 participants pre and post
      legislation and analysed using the framework approach. Self-report surveys were
      completed by 129 participants pre and post legislation, and responses were
      subject to quantitative analyses. RESULTS: Improvements in allergen information
      provision and raised awareness of food allergy in eating out venues were reported
      following introduction of EU FIC. Whilst participants favoured written allergen
      information, they expressed greater confidence in communicating with eating out
      staff and in trusting the allergen information that they provided. Improvements
      were judged to be gradual, sporadic or inconsistent in implementation. CONCLUSION
      & CLINICAL RELEVANCE: For many participants, the "ideal" eating out experience
      was one in which a range of information resources were available and where
      written allergen information was complemented by proactive and accommodating
      staff within an allergy-aware environment. Whilst the onus is on legislators and
      food providers to ensure that adequate allergen information is provided,
      clinicians play an important role in encouraging patients with food allergy to
      pursue their legal right to make allergen enquiries to avoid accidental allergen
      ingestion when eating out.

PMID- 29220105
TI  - Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A
      mechanism behind reduced cardiovascular mortality?
AB  - BACKGROUND: In an intervention study where 221 healthy elderly persons received
      selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4
      years we observed improved cardiac function and reduced cardiovascular mortality.
      As fibrosis is central in the aging process, we investigated the effect of the
      intervention on biomarkers of fibrogenic activity in a subanalysis of this
      intervention study. MATERIAL AND METHODS: In the present subanalysis 122 actively
      treated individuals and 101 controls, the effect of the treatment on eight
      biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin
      S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix
      Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and
      Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers
      after 6 and 42 months were analyzed by the use of T-tests, repeated measures of
      variance, and factor analyses. RESULTS: Compared with placebo, in those receiving
      supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed
      significant decreased concentrations in blood. The changes in concentrations,
      that is, effects sizes as given by partial eta2 caused by the intervention were
      considered small to medium. CONCLUSION: The significantly decreased biomarker
      concentrations in those on active treatment with selenium and coenzyme Q10
      compared with those on placebo after 36 months of intervention presumably reflect
      less fibrogenic activity as a result of the intervention. These observations
      might indicate that reduced fibrosis precedes the reported improvement in cardiac
      function, thereby explaining some of the positive clinical effects caused by the
      intervention. (c) 2017 BioFactors, 44(2):137-147, 2018.

PMID- 29220106
TI  - Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic
      regulation.
AB  - Epigenetic mechanisms are essential in regulating normal cellular functions and
      play an important role during the disease developmental stages. However, aberrant
      epigenetic mechanisms may lead to pathological consequences such as cancer,
      neurological disorders, bone and skeletal diseases, cardiovascular dysfunction,
      and metabolic syndrome. The molecular mechanisms of epigenetic modification
      include DNA methylation, histone modification (acetylation, methylation and
      phosphorylation), and microRNAs (miRNAs). Unlike genetic modifications,
      epigenetic states of genes are reversible and can be altered by certain intrinsic
      and extrinsic factors. In the past few decades, accumulated evidence shows that
      dietary phytochemicals with chemopreventive effects are also potent epigenetic
      regulators. Resveratrol and pterostilbene are stilbenoids, which have been
      reported to have anti-cancer, anti-inflammatory, anti-lipid, and anti-diabetic
      properties. Stilbenoids are also reported to improve cardiovascular disease. By
      altering DNA methylation and histone modification or by modulating miRNA
      expression, resveratrol, and pterostilbene become potent epigenetic modifiers. In
      this review, we summarize these studies and underlying mechanisms of resveratrol
      and pterostilbene and their influence on epigenetic mechanisms. (c) 2017
      BioFactors, 44(1):26-35, 2018.

PMID- 29220108
TI  - Photocatalytic Aerobic Phosphatation of Alkenes.
AB  - A catalytic regime for the direct phosphatation of simple, non-polarized alkenes
      has been devised that is based on using ordinary, non-activated phosphoric acid
      diesters as the phosphate source and O2 as the terminal oxidant. The title method
      enables the direct and highly economic construction of a diverse range of allylic
      phosphate esters. From a conceptual viewpoint, the aerobic phosphatation is
      entirely complementary to traditional methods for phosphate ester formation,
      which predominantly rely on the use of prefunctionalized or preactivated
      reactants, such as alcohols and phosphoryl halides. The title transformation is
      enabled by the interplay of a photoredox and a selenium pi-acid catalyst and
      involves a sequence of single-electron-transfer processes.

PMID- 29220109
TI  - Population transcriptomics in Daphnia: The role of thermal selection.
AB  - The complex interplay of forces influencing genetic divergence among populations
      complicates the discovery of the genetic basis underlying local adaptation. Here,
      we utilized for the first time a combined reverse ecology and population
      transcriptomic approach to assess the contribution of thermal selection to
      population differentiation, thereby considering transcriptome-wide variation in
      both gene expression profiles and DNA sequences. We compared transcriptomes among
      four Daphnia galeata populations and identified transcripts potentially
      responding to local thermal selection based on an extensive literature search for
      candidate genes possibly under thermal selection in arthropods. Over
      representation of temperature-relevant candidate genes among transcripts strongly
      contributing to sequence divergence among two populations indicates that local
      thermal selection acted on the coding sequence level. We identified a large
      number of transcripts, which may contribute to local thermal adaptation based on
      outlier tests and distinctive expression profiles. However, among these,
      temperature-relevant candidate genes were not over-represented compared to the
      global gene set, suggesting that thermal selection played a minor role in
      divergence among Daphnia populations. Interestingly, although the majority of
      genes contributing strongly to sequence divergence did not contribute strongly to
      divergence at the expression level and vice versa, the affected gene functions
      were largely consistent between the two data sets. This suggests that genetic and
      regulatory variation constitutes alternative routes for responses to natural
      selection. Our combined utilization of a population transcriptomics approach and
      literature-based identification of ecologically informative candidate genes
      represents a useful and powerful methodology with a wide range of applications in
      evolutionary biology.

PMID- 29220110
TI  - Nonresponsiveness and Susceptibility of Opioid Side Effects Related to Cancer
      Patients' Clinical Characteristics: A Post-Hoc Analysis.
AB  - BACKGROUND: The response to opioids is not always positive in cancer patients. A
      considerable proportion of patients do not respond (nonresponders [NRs]) or
      experience severe toxicity. The aim of this analysis was to assess the role of
      demographic characteristics, pain features, comorbidities, and ongoing therapy on
      the lack of efficacy and on the occurrence of severe adverse drug reactions
      (ADRs). METHODS: This is a post-hoc analysis of a randomized controlled trial
      that involved 520 patients and aimed to evaluate the efficacy and safety of 4
      strong opioids. Patients who presented with unchanged or worsened pain compared
      to the first visit were considered to be NRs. As for toxicity, severe ADRs with
      an incidence of greater than 10% were evaluated. Univariate and multivariate
      logistic models were used. RESULTS: 498 patients were analyzed. Liver metastases
      and breakthrough pain (BTP) were found to increase the risk for nonresponse.
      Conversely, a high basal pain intensity significantly decreased the same risk.
      Constipation risk was worsened by previous weak opioid therapy but decreased with
      aging and with the use of transdermal opioids. Risk for drowsiness was aggravated
      by bone metastases and concomitant treatment with anticoagulant, antidiabetic,
      and central nervous system drugs. Risk for confusion increased with
      antidiabetics, antibiotics, and previous weak opioid therapy but decreased when
      fentanyl was used. Occurrence of nausea increased in patients with a high rating
      on the Karnofsky Performance Status Index. Risk for xerostomia was higher in
      women and in patients treated with antidiabetic or long-term opioids.
      CONCLUSIONS: Several clinical variables are correlated with opioid response in
      cancer patients. In particular, the presence of BTP is associated with
      nonresponse. Additionally, patients who receive polypharmacological therapy are
      more likely to experience opioid adverse events.

PMID- 29220111
TI  - Phosphoenolpyruvate Transporter Enables Targeted Perturbation During Metabolic
      Analysis of L-Phenylalanine Production With Escherichia coli.
AB  - Usually perturbation of the metabolism of cells by addition of substrates is
      applied for metabolic analysis of production organisms, but perturbation studies
      are restricted to the endogenous substrates of the cells under study. The goal of
      this study is to overcome this limitation by making phosphoenolpyruvate (PEP)
      available for perturbation studies with Escherichia coli producing L
      phenylalanine. A production strain overexpressing a PEP-transporter variant (UhpT
      D388C) is applied in a standardized fed-batch production-process on a 42 L-scale.
      Four parallel short-term perturbation experiments of 20 min are performed with
      glucose and glycerol as fed-batch carbon sources after rapid media transition of
      cells from the production-process. PEP is added after 9 min and is immediately
      consumed by the cells with up to 1.5 mmol gCDW-1  h-1 . L-phenylalanine
      production rates increased by up to 200% after addition of PEP. This clearly
      indicates an intracellular PEP-limitation in the L-phenylalanine production
      strain under study. Thus, it is shown that overexpressing specific transporters
      for analytical reasons makes exogenous substrates available as perturbation
      substrates for metabolic analyses of cells sampled from production-processes and
      thereby allows a very targeted perturbation of whole-cell metabolism.

PMID- 29220112
TI  - Multispectral image analysis in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To investigate fundus abnormalities in Vogt-Koyanagi-Harada (VKH)
      disease by a noninvasive tool, multispectral imaging (MSI). METHODS: A total of
      77 patients with VKH and 163 healthy controls were enrolled between January and
      April 2015. The MSI findings were evaluated in combination with fundus
      fluorescein angiography (FFA), optical coherent tomography (OCT) and fundus
      photography (FP). Additionally, we compared extent of exposure of choroidal blood
      vessels between patients with VKH and healthy controls to evaluate retinal
      transmission function. RESULTS: A number of features could be recognized by MSI
      which included (i) general depigmentation, (ii) clumping of pigment and (iii)
      macular depigmentation and/or hyperpigmentation. The percentages of these three
      abnormalities discovered by MSI in 52 inactive VKH patients with a duration of
      more than 2 months in VKH were 67.3%, 75% and 84.6% respectively, which were all
      significantly higher than those detected by FFA, OCT or FP (p = 0.0398, p <
      0.0001). Our study showed that MSI detected a higher percentages of these four
      abnormalities in patients with sunset glow fundus than in patients without this
      phenomenon (p = 0.0492, p < 0.0001). Additionally, at the same wavelength (590
      nm), exposure of choroidal blood vessels in inactive patients was stronger than
      in healthy controls and active patients (p < 0.01, p < 0.001). CONCLUSION: Our
      results show that MSI is a sensitive noninvasive method to investigate the
      retinal pigment epithelium (RPE) in VKH disease. It is more likely to detect RPE
      abnormalities with MSI than when using FFA, OCT or FP. Retinal transmission
      function in inactive patients is stronger than that observed in active patients
      or healthy controls.

PMID- 29220113
TI  - Effect of dexamethasone intravitreal implant on blood glucose, hypothalamic
      pituitary-adrenal axis function and vascular endothelial growth factor serum
      levels in patients with diabetic macular oedema.

PMID- 29220114
TI  - Treat-and-extend versus every-other-month regimens with aflibercept in age
      related macular degeneration.
AB  - PURPOSE: To compare the 1-year outcomes of treat-and-extend (TAE) and every-other
      month (2M) regimens with intravitreal aflibercept in Japanese wet age-related
      macular degeneration (AMD) patients. METHODS: Prospective, multicenter,
      randomized clinical trial. The primary outcome measure was the proportion of eyes
      in which the best-corrected visual acuity (BCVA) was maintained at week 52 [with
      a loss of <0.3 logarithm of minimum angular of resolution (logMAR) units]. The
      secondary outcome measures were the mean change from baseline in the central
      retinal thickness (CRT) and the number of injections. RESULTS: Forty-one patients
      were enrolled. The mean changes in the BCVA from baseline in the TAE and 2M were 
      0.32 +/- 0.27 and -0.26 +/- 0.30 logMAR units (p = 0.46). The TAE group was
      noninferior to the 2M group in BCVA maintenance. The mean CRT changes from
      baseline in the TAE and 2M were -161 +/- 133 and -157 +/- 90 MUm (p = 0.73). The
      mean number of injections in the TAE and 2M were 7.5 +/- 1.2 (range, 7-12) and
      8.0 +/- 0.0 (p < 0.0001). CONCLUSION: Treat-and-extend (TAE) regimen with
      aflibercept improved the BCVA and CRT to the same extent as 2M regimen, with a
      reduced number of injections.

PMID- 29220115
TI  - HIV prevention where it is needed most: comparison of strategies for the
      geographical allocation of interventions.
AB  - INTRODUCTION: A strategic approach to the application of HIV prevention
      interventions is a core component of the UNAIDS Fast Track strategy to end the
      HIV epidemic by 2030. Central to these plans is a focus on high-prevalence
      geographies, in a bid to target resources to those in greatest need and maximize
      the reduction in new infections. Whilst this idea of geographical prioritization
      has the potential to improve efficiency, it is unclear how it should be
      implemented in practice. There are a range of prevention interventions which can
      be applied differentially across risk groups and locations, making allocation
      decisions complex. Here, we use mathematical modelling to compare the impact
      (infections averted) of a number of different approaches to the implementation of
      geographical prioritization of prevention interventions, similar to those
      emerging in policy and practice, across a range of prevention budgets. METHODS:
      We use geographically specific mathematical models of the epidemic and response
      in 48 counties and major cities of Kenya to project the impact of the different
      geographical prioritization approaches. We compare the geographical allocation
      strategies with a nationally uniform approach under which the same interventions
      must be applied across all modelled locations. RESULTS: We find that the most
      extreme geographical prioritization strategy, which focuses resources exclusively
      to high-prevalence locations, may substantially restrict impact (41% fewer
      infections averted) compared to a nationally uniform approach, as opportunities
      for highly effective interventions for high-risk populations in lower-prevalence
      areas are missed. Other geographical allocation approaches, which intensify
      efforts in higher-prevalence areas whilst maintaining a minimum package of cost
      effective interventions everywhere, consistently improve impact at all budget
      levels. Such strategies balance the need for greater investment in locations with
      the largest epidemics whilst ensuring higher-risk groups in lower-priority
      locations are provided with cost-effective interventions. CONCLUSIONS: Our
      findings serve as a warning to not be too selective in the application of
      prevention strategies. Further research is needed to understand how decision
      makers can find the right balance between the choice of interventions, focus on
      high-risk populations, and geographical targeting to ensure the greatest impact
      of HIV prevention.

PMID- 29220116
TI  - Advances in Microfluidics Applied to Single Cell Operation.
AB  - The field of microbiology have traditionally been concerned with and focused on
      studies at the population level. Microfluidic platforms have emerged as important
      tools for biology research at a small scale, even down to a single cell level.
      The spatial and temporal control of cells and stimuli transported by microfluidic
      channels in well-designed microsystems realized the studies of specific cells in
      a controlled microenvironment. The true cellular physiology responses, which are
      obtained mostly by inference from population-level data, could be revealed in
      this way. Nowadays, significant applications like cell culture, analysis,
      sorting, genomics, and proteomics at the single cell level have been achieved in
      microfluidic chips. Highly integrated microfluidic systems with complete bio
      analytic functions are also coming forth and of great promise for single cell
      related physiology, biomedical, and high throughput screening research. Herein,
      the leads of technologies applied to single cell operation are reviewed.
      Challenges and potentials of these works are also summarized, to highlight fields
      for further research.

PMID- 29220117
TI  - Anterior surface breakdown and implant extrusion following secondary alloplastic
      orbital implantation surgery.
AB  - BACKGROUND: Secondary orbital implantation surgery can be complex due to scarring
      of the orbital tissues and can be complicated by implant exposure and extrusion.
      PURPOSE: To evaluate the incidence and risk factors of implant exposure and
      extrusion following secondary alloplastic orbital implantation surgery in
      anophthalmic patients. METHODS: Retrospective analysis of a consecutive series of
      patients who underwent secondary placement of an alloplastic orbital implant by
      one surgeon between 2001 and 2016 in the Rotterdam Eye Hospital. OUTCOME
      PARAMETERS: implant exposure or extrusion. Other complications. RESULTS: Sixty
      three patients underwent secondary orbital placement of scleral-wrapped acrylic
      (60) or silicone (three) spherical implants. A subset of 25 patients had
      undergone earlier secondary orbital implant placement (by other surgeons) with
      exposure/extrusion necessitating additional implant surgery. Two patients were
      excluded due to lack of follow-up (<3 months). Mean age was 49 years (range: 1
      84.5 years). The mean follow-up was 4.1 years (range: 0.25-13, 6 years). Implant
      exposure or extrusion occurred in six of 18 (33%) patients in whom no muscle had
      been reattached during secondary orbital implantation and in five of 43 (12%)
      patients in whom the extraocular recti muscles had been attached, but the follow
      up time was shorter for the latter group. Surgical treatment for implant
      exposure/extrusion was required in eleven of 61 patients (18%). Other
      complications included postoperative volume deficiency despite optimal prosthesis
      (five of 61, 8%), inclusion cysts (four of 61, 7%) and conjunctivitis sicca (two
      of 61, 3%). Seven of 61 (11%) patients required fornix deepening and seven (11%)
      blepharoptosis correction. CONCLUSION: Secondary orbital implantation of sclera
      wrapped alloplastic implants was complicated by implant extrusion or exposure in
      12% of cases in which the extraocular muscles were attached to the implant.

PMID- 29220118
TI  - Traditional and molecular chromosomal abnormality analysis of products of
      conception in spontaneous and recurrent miscarriage.
AB  - : Chromosome abnormalities account for half of the recorded miscarriages. Data
      from cytogenetic analysis of the products of conception (POC) in miscarriages are
      reviewed in the paper. Genetic analysis of POC allows patients to be given
      prognostic information. Molecular genetic techniques can overcome the pitfalls of
      conventional karyotyping, such as culture failure and trace submicroscopic
      abnormalities. We compare the pros and cons when these technologies are applied
      to the analysis of POC after miscarriage. Guidance is also provided for future
      clinical applications. The objective of the review is to help clinicians
      understand the limitations and to optimise the usefulness of genetic analysis of
      POC. TWEETABLE ABSTRACT: Genetics and POC of miscarriage.

PMID- 29220119
TI  - Identification of the novel HLA-DQB1*03:181 allele in a Chinese leukemia patient.
AB  - HLA-DQB1*03:181 has one nucleotide change from HLA-DQB1*03:05:01 at position
      470C>G.

PMID- 29220120
TI  - Efavirenz is related to neuropsychiatric symptoms among adults, but not among
      adolescents living with human immunodeficiency virus in Kilimanjaro, Tanzania.
AB  - OBJECTIVES: To explore the relationship between Efavirenz (EFV) and
      neuropsychiatric symptoms among adults and adolescents living with human
      immunodeficiency virus (HIV) in Kilimanjaro, Tanzania. METHODS: Cross-sectional
      study among HIV-infected adults (age 18-65) and adolescents (age 12-17) on
      antiretroviral treatment attending Kilimanjaro Christian Medical Centre, Moshi,
      Tanzania. Neuropsychiatric symptoms were measured using the Hospital Anxiety and
      Depression Scale (HADS), the Symptom Checklist 90 (SCL-90) and the Mini
      International Neuropsychiatric Interview (MINI). manova and chi-squared tests
      were used to test differences between EFV and non-EFV-treated participants.
      RESULTS: A total of 215 adults and 150 adolescents participated. About 52% of
      adults and 37% of adolescents used EFV. Among adults, depression scores were
      higher for those on EFV (HADS (Cohen's D: 0.38; P = 0.02) and SCL-90 (Cohen's D:
      0.24; P = 0.03). Among adolescents, those on EFV had lower scores on depression
      (HADS (Cohen's D: 0.3; P = 0.02) and SCL-90 (Cohen's D: 0.1; P = 0.02). About 10%
      of adults reported suicidal thoughts, but there was no difference between those
      on EFV and those without. Lastly, adults on EFV reported higher levels of
      problematic alcohol use (P = 0.003). CONCLUSIONS: In line with the previous
      studies, EFV is associated with depressive symptoms and problematic alcohol use
      among HIV-infected adults in Tanzania. In contrast, EFV was associated with lower
      levels of depressive symptoms in adolescents in Tanzania. Particularly among
      adults, close monitoring of depressive symptoms and alcohol use is indicated.

PMID- 29220121
TI  - Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation:
      Results of the PROCO Randomized Controlled Trial.
AB  - OBJECTIVE: The PROCO RCT is a multicenter, double-blind, crossover, randomized
      controlled trial (RCT) that investigated the effects of rate on analgesia in
      kilohertz frequency (1-10 kHz) spinal cord stimulation (SCS). MATERIALS AND
      METHODS: Patients were implanted with SCS systems and underwent an eight-week
      search to identify the best location ("sweet spot") of stimulation at 10 kHz
      within the searched region (T8-T11). An electronic diary (e-diary) prompted
      patients for pain scores three times per day. Patients who responded to 10 kHz
      per e-diary numeric rating scale (ED-NRS) pain scores proceeded to double-blind
      rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet
      spot found for 10 kHz in randomized order (four weeks at each frequency). For
      each frequency, pulse width and amplitude were titrated to optimize therapy.
      RESULTS: All frequencies provided equivalent pain relief as measured by ED-NRS (p
      <= 0.002). However, mean charge per second differed across frequencies, with 1
      kHz SCS requiring 60-70% less charge than higher frequencies (p <= 0.0002).
      CONCLUSIONS: The PROCO RCT provides Level I evidence for equivalent pain relief
      from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz
      required significantly less charge than higher frequencies.

PMID- 29220123
TI  - Dorsal Root Ganglion Stimulation: A Treatment Option for Chronic Pain Due to
      Refractory Loin Pain Haematuria Syndrome.

PMID- 29220124
TI  - RE: Juch JNS, et al. Effect of Radiofrequency Denervation on Pain Intensity Among
      Patients With Chronic Low Back Pain: The Mint Randomized Clinical Trials. JAMA
      2017;318(1):68-81.

PMID- 29220122
TI  - Expression profile analysis of long non-coding RNA in acute myeloid leukemia by
      microarray and bioinformatics.
AB  - Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are
      involved in tumorigenesis and play a key role in cancer progression. To determine
      whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the
      expression profile of lncRNAs and mRNAs in AML. Five pairs of AML patients and
      iron deficiency anemia (IDA) controls were screened by microarray. Through
      coexpression analysis, differently expressed transcripts were divided into
      modules, and lncRNAs were functionally annotated. We further analyzed the
      clinical significance of crucial lncRNAs from modules in public data. Finally,
      the expression of three lncRNAs, RP11-222K16.2, AC092580.4, and RP11-305O.6, were
      validated in newly diagnosed AML, AML relapse, and IDA patient groups by
      quantitative RT-PCR, which may be associated with AML patients' overall survival.
      Further analysis showed that RP11-222K16.2 might affect the differentiation of
      natural killer cells, and promote the immunized evasion of AML by regulating
      Eomesodermin expression. Analysis of this study revealed that dysregulated
      lncRNAs and mRNAs in AML vs IDA controls could affect the immune system and
      hematopoietic cell differentiation. The biological functions of those lncRNAs
      need to be further validated.

PMID- 29220126
TI  - Can the retina be used to diagnose and plot the progression of Alzheimer's
      disease?
AB  - Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause
      of senile dementia. It impairs the quality of life of a person and their family,
      posing a serious economic and social threat in developed countries. The fact that
      the diagnosis can only be definitively made post-mortem, or when the disease is
      fairly advanced, presents a serious problem if novel therapeutic interventions
      are to be devised and used early in the course of the disease. There is therefore
      a pressing need for more sensitive and specific diagnostic tests with which we
      can detect AD in the preclinical stage. The tau proteins and beta-amyloid
      proteins start to accumulate 20 years before the symptoms begin to manifest.
      Detecting them in the preclinical stage would be a potential breakthrough in the
      management of AD. A high degree of clinical suspicion is needed to correlate
      problems in cognition with the changes in the eye, particularly the retina, pupil
      and ocular movements, so that the disease can be detected early and managed in
      the prodromal phase. In this systematic review, we ask the question whether the
      retina can be used to make a specific and early diagnosis of AD.

PMID- 29220127
TI  - Vascular endothelial growth factor inhibition for proliferative diabetic
      retinopathy: Et tu, Brute?

PMID- 29220128
TI  - Trauma Resuscitation: An evidence-based review of prehospital traumatic cardiac
      arrest.

PMID- 29220129
TI  - Damage Control: Resuscitation.

PMID- 29220130
TI  - Wound Packing 101: Hemorrhage control when it's more than skin deep.

PMID- 29220131
TI  - JEMS selects top 10 innovators of 2016.

PMID- 29220132
TI  - Active Seizures: Guidelines for treatment of prolonged seizures in children and
      adults.

PMID- 29220133
TI  - Emergence of EMS in India: India's budding EMS infrastructure is a model for the
      region despite challenges moving forward.

PMID- 29220134
TI  - MODELLING midwifery care.

PMID- 29220135
TI  - NARCOLEPSY. The Body Systems Training Room (BSTR) is the fourth of ANMF's CPD
      training room for nurses and midwives.

PMID- 29220136
TI  - Can't Get No Satisfaction: Measuring quality in EMS.

PMID- 29220137
TI  - How to create a calm and confident mindset.

PMID- 29220138
TI  - Smart nurses thoughtless posts on social media.

PMID- 29220139
TI  - Hands On: Product Reviews From Street Crews.

PMID- 29220141
TI  - Last Word: the Ups and Downs of EMS.

PMID- 29220140
TI  - The fast lane: Nursing in WA's busiest emergency department.

PMID- 29220142
TI  - Cultural competence in emergency department.

PMID- 29220143
TI  - Midwifery excellence delivering a new generation.

PMID- 29220144
TI  - Patient stories about being cared for in the emergency department.

PMID- 29220145
TI  - Emergency nurses a breed of their own.

PMID- 29220146
TI  - Unscheduled returns to the emergency department.

PMID- 29220147
TI  - Unscheduled returns to the emergency department.

PMID- 29220148
TI  - The lifespan of peripheral IVs inserted in the paediatric ED: do they go the
      distance?

PMID- 29220149
TI  - The Future is Now: Harnessing advanced technology to save money and save lives.

PMID- 29220150
TI  - Functionalized Eu(III)-Based Nanoscale Metal-Organic Framework To Achieve Near-IR
      Triggered and -Targeted Two-Photon Absorption Photodynamic Therapy.
AB  - The postsynthetic-modified nanoscale metal-organic framework (NMOF) probes
      selected as potential drug delivery platforms and photodynamic therapy agents to
      fulfill the effective and safe treatment of neoplastic diseases have attracted
      increasing attention recently. Herein, a Eu(III)-based NMOF probe elaborately
      postsynthetically modified with a beta-diketonate two-photon-absorbing (TPA)
      ligand is rationally designed and further functionalized by assembling the
      photosensitizer molecule (methylene blue, MB) in the pores and a cyclic peptide
      targeting motif on the surface of the NMOF, which could achieve highly efficient
      near-infrared (NIR)-triggered and -targeted photodynamic therapy (PDT). On the
      basis of the luminescence resonance energy transfer process between the NMOF
      donor and the photosensitizer MB acceptor, the probe can achieve a high tissue
      penetrable TPA-PDT effect. Thus, the NMOFs in this study play the role of not
      only the nanocontainer for the photosensitizer but also the energy-transfer
      donor. Studies in vitro show enhanced cellular uptake and satisfactory PDT
      effectiveness toward cancer cells compared to the free photosensitizer MB. It is
      highly expected that this study contributes to the development of smart
      luminescent diagnostic and therapeutic probes.

PMID- 29220151
TI  - Integration of Enzymes in Polyaniline-Sensitized 3D Inverse Opal TiO2
      Architectures for Light-Driven Biocatalysis and Light-to-Current Conversion.
AB  - Inspired by natural photosynthesis, coupling of artificial light-sensitive
      entities with biocatalysts in a biohybrid format can result in advanced
      photobioelectronic systems. Herein, we report on the integration of sulfonated
      polyanilines (PMSA1) and PQQ-dependent glucose dehydrogenase (PQQ-GDH) into
      inverse opal TiO2 (IO-TiO2) electrodes. While PMSA1 introduces sensitivity for
      visible light into the biohybrid architecture and ensures the efficient wiring
      between the IO-TiO2 electrode and the biocatalytic entity, PQQ-GDH provides the
      catalytic activity for the glucose oxidation and therefore feeds the light-driven
      reaction with electrons for an enhanced light-to-current conversion. Here, the IO
      TiO2 electrodes with pores of around 650 nm provide a suitable interface and
      morphology needed for the stable and functional assembly of polymer and enzyme.
      The IO-TiO2 electrodes have been prepared by a template approach applying spin
      coating, allowing an easy scalability of the electrode height and surface area.
      The successful integration of the polymer and the enzyme is confirmed by the
      generation of an anodic photocurrent, showing an enhanced magnitude with
      increasing glucose concentrations. Compared to flat and nanostructured TiO2
      electrodes, the three-layered IO-TiO2 electrodes give access to a 24-fold and 29
      fold higher glucose-dependent photocurrent due to the higher polymer and enzyme
      loading in IO films. The three-dimensional IO-TiO2|PMSA1|PQQ-GDH architecture
      reaches maximum photocurrent densities of 44.7 +/- 6.5 MUA cm-2 at low potentials
      in the presence of glucose (for a three TiO2 layer arrangement). The onset
      potential for the light-driven substrate oxidation is found to be at -0.315 V vs
      Ag/AgCl (1 M KCl) under illumination with 100 mW cm-2, which is more negative
      than the redox potential of the enzyme. The results demonstrate the advantageous
      properties of IO-TiO2|PMSA1|PQQ-GDH biohybrid architectures for the light-driven
      glucose conversion with improved performance.

PMID- 29220152
TI  - Meltwater Evolution during Defrosting on Superhydrophobic Surfaces.
AB  - Defrosting is essential for removing frost from engineering surfaces, but some
      fundamental issues are still unclear, especially for defrosting on
      superhydrophobic surfaces. Here, defrosting experiments on prepared
      superhydrophobic surfaces were conducted along with the investigation on
      meltwater evolution characteristics. According to the experiments, the typical
      meltwater evolution process on superhydrophobic surfaces can be divided into two
      stages: dewetting by edge curling and dewetting by shrinkage. The edge curling of
      a meltwater film is a distinct phenomenon and has been first reported in this
      work. Profiting from the ultralow adhesion of the superhydrophobic surface, edge
      curling is mainly attributed to two unbalanced forces (one at the interface
      between the ice slurry layer and pure water layer and the other in the triple
      phase line area) acting on the layered meltwater film. During the multi-meltwater
      evolution process, the nonbreaking of chained droplets on superhydrophobic
      surfaces is also an interesting phenomenon, which is controlled by the
      interaction between the surface tension and the retentive force because of
      contact angle hysteresis. An approximate criterion was then developed to explain
      and determine the status of chained droplets, and experimental data from various
      surfaces have validated the effectiveness of this criterion. This work may deepen
      the understanding of defrosting on superhydrophobic surfaces and promote
      antifrosting/icing applications in engineering.

PMID- 29220153
TI  - Rim-Differentiated C5-Symmetric Tiara-Pillar[5]arenes.
AB  - The synthesis of "rim-differentiated" C5-symmetric pillar[5]arenes, whose two
      rims are decorated with different chemical functionalities, has remained a
      challenging task. This is due to the inherent statistical nature of the
      cyclization of 1,4-disubstituted alkoxybenzenes with different substituents,
      which leads to four constitutional isomers with only 1/16th being rim
      differentiated. Herein, we report a "preoriented" synthetic protocol based on
      FeCl3-catalyzed cyclization of asymmetrically substituted 2,5-dialkoxybenzyl
      alcohols. This yields an unprecedented 55% selectivity of the C5-symmetric tiara
      like pillar[5]arene isomer among four constitutional isomers. Based on this new
      method, a series of functionalizable tiara-pillar[5]arene derivatives with C5
      symmetry was successfully synthesized, isolated, and fully characterized in the
      solid state.

PMID- 29220154
TI  - Set of Multifunctional Azo Functionalized Semiconducting Cd(II)-MOFs Showing
      Photoswitching Property and Selective CO2 Adsorption.
AB  - Syntheses, structural characterizations, photoluminescence, and adsorption
      properties of three new azo-functionalized Cd(II)-MOFs, namely,
      {[Cd(azbpy)(msuc)].2.5(H2O)}n (2), {[Cd(azbpy)(mglu)].5(H2O)}n (3), and
      {[Cd1.5(azbpy)2(glu)].(NO3).MeOH}n (4) [where msuc2- = methylsuccinate; mglut2- =
      methylglutarate; glut2- = glutarate; azbpy = 4,4'-azobispyridine] have been
      reported. The compounds show different structures only with the variation of
      aliphatic dicarboxylates. The photoswitching behavior for the above-mentioned
      newly synthesized Cd(II)-MOFs along with one of our previously reported other azo
      functionalized Cd(II)-MOF, namely, {[Cd(azbpy)(suc)].2(H2O)}n (1), has been
      studied extensively. At photoilluminated condition, the conductivity values can
      draw a clear structure-property relationship among the structures of compounds 1
      4. Single crystal structural analysis reveals that all the compounds exhibit a
      three-dimensional (3D) framework connected by azbpy linker and respective
      aliphatic dicarboxylate through their bis-chelating mono/bis oxo-bridging
      fashion. Compounds 1-3 exhibit an iso-structural honeycomb like 3D framework
      showing the same coordination environments, where the metal-carboxylate 2D sheets
      of compounds 1-3 are pillared by N,N'-donor azbpy linkers. On the other hand,
      compound 4 exhibits a 2-fold interpenetrated 3D framework with a little
      difference in its coordination environment and the pillaring of 1D metal
      carboxylate ladder by azbpy linkers. All the compounds significantly demonstrate
      their enhanced sensitivity under light rather than the dark condition. The gas
      and solvent vapor sorption studies have been performed for the synthesized
      compounds 2-4. Moreover, compound 2 exhibits an enhanced type IV selective CO2
      adsorption isotherm over N2 along with the appearance of gate opening phenomena
      in that.

PMID- 29220157
TI  - Molecular Structure Characterization by Isotopic Splitting in Nonlinear Ion
      Mobility Spectra.
AB  - Nearly all compounds comprise numerous isotopologues ensuing from stable natural
      isotopes for constituent elements. The consequent isotopic envelopes in mass
      spectra can reveal the ion stoichiometry but not geometry. We found those
      envelopes to split in differential ion mobility (FAIMS) spectra in a manner
      dependent on the ion geometry and buffer gas composition. The resulting
      multidimensional matrix of isotopic shifts is specific to isomers, providing a
      fundamentally new approach to the characterization of chemical structure. The
      physical origins of the effect remain to be clarified but likely ensue from the
      transposition of center of mass of the ion within its geometry frame affecting
      the partition of energy in above-thermal collisions between the translational and
      rotational degrees of freedom. The additivity of shifts, holding with no
      exception so far, may be the key to unraveling the foundations of observed
      behavior.

PMID- 29220155
TI  - Superchiral Plasmonic Phase Sensitivity for Fingerprinting of Protein Interface
      Structure.
AB  - The structure adopted by biomaterials, such as proteins, at interfaces is a
      crucial parameter in a range of important biological problems. It is a critical
      property in defining the functionality of cell/bacterial membranes and biofilms
      (i.e., in antibiotic-resistant infections) and the exploitation of immobilized
      enzymes in biocatalysis. The intrinsically small quantities of materials at
      interfaces precludes the application of conventional spectroscopic phenomena
      routinely used for (bio)structural analysis due to a lack of sensitivity. We show
      that the interaction of proteins with superchiral fields induces asymmetric
      changes in retardation phase effects of excited bright and dark modes of a chiral
      plasmonic nanostructure. Phase retardations are obtained by a simple procedure,
      which involves fitting the line shape of resonances in the reflectance spectra.
      These interference effects provide fingerprints that are an incisive probe of the
      structure of interfacial biomolecules. Using these fingerprints, layers composed
      of structurally related proteins with differing geometries can be discriminated.
      Thus, we demonstrate a powerful tool for the bioanalytical toolbox.

PMID- 29220156
TI  - Ultrathin N-Doped Mo2C Nanosheets with Exposed Active Sites as Efficient
      Electrocatalyst for Hydrogen Evolution Reactions.
AB  - Probing competent electrocatalysts for hydrogen evolution reaction (HER) of water
      splitting is one of the most hopeful approaches to confront the energy and
      environmental crisis. Herein, we highlight ultrathin N-doped Mo2C nanosheets (N
      Mo2C NSs) in the role of greatly efficient platinum-free-based electrocatalysts
      for the HER. The transformation of crystal phase and structure between MoO2
      nanosheets with a thickness of ~1.1 nm and N-Mo2C NSs with a thickness of ~1.0 nm
      is studied in detail. Structural analyses make clear that the surfaces of the N
      Mo2C NSs are absolutely encompassed by apical Mo atoms, hence affording an ideal
      catalyst prototype to expose the role of Mo atoms for the duration of HER
      catalysis. Theoretical calculations demonstrate that the nanosheet structure, N
      doping, and particular crystalline phase of Mo2C produce more exposed Mo active
      sites, including Mo atoms on the C plane and doped N atoms. Through detailed
      electrochemical investigations, N-Mo2C NSs possess HER activity with an onset
      potential of -48.3 mV vs RHE, Tafel slope of 44.5 mV dec-1, and overpotential of
      99 mV vs RHE at the cathodic current density of 10 mA cm-2 with excellent long
      term stability. Lastly, the calcination temperature and dicyandiamide amount can
      obviously affect the phase transformation and surface structure of molybdenum
      carbide, resulting in an adjustable HER activity. This synthesis mechanism will
      facilitate the understanding and optimization of Mo-based electrocatalysts in the
      energy conversion field.

PMID- 29220158
TI  - Mixed NiO/NiCo2O4 Nanocrystals Grown from the Skeleton of a 3D Porous Nickel
      Network as Efficient Electrocatalysts for Oxygen Evolution Reactions.
AB  - Mixed NiO/NiCo2O4 nanocrystals grown in situ from the skeleton of a 3D porous
      nickel network (3DPNN) were prepared with a simple hydrothermal method followed
      by a low temperature calcination, exhibiting outstanding electrocatalytic
      efficiencies toward oxygen evolution reactions (OER). The 3DPNN was prepared with
      a novel leaven dough method and served as both the nickel source for growth of
      the mixed NiO/NiCo2O4 nanocrystals and the charge transport highway to accelerate
      the sluggish kinetics of the OER. The mixed NiO/NiCo2O4 nanocrystals exhibited
      pronounced synergistic effects to achieve a high mass activity of 200 A g-1 at
      the catalyst mass loading of 0.5 mg cm-2, largely outperforming the corresponding
      single component nanocrystal systems, NiO (5.87) and NiCo2O4 (9.35). The
      NiO/NiCo2O4@3DPNN composite electrocatalyst achieved a low overpotential of 264
      mV at the current density of 10 mA cm-2 and 389 mV at the practically high
      current density of 250 mA cm-2, which compete favorably among the top tier of
      previously reported OER electrocatalysts. Moreover, it exhibited good stability
      even at the high current density of 250 mA cm-2, showing only 9.40% increase in
      working applied potential after a continuous 12 h operation. The present work
      demonstrates a new design for highly efficient OER catalysts with in situ growth
      of mixed oxide nanocrystals of pronounced synergistic effects.

PMID- 29220159
TI  - Monolithic Nanoporous In-Sn Alloy for Electrochemical Reduction of Carbon
      Dioxide.
AB  - Nanostructured metal catalysts to convert CO2 to formate, which have been
      extensively studied over decades, have many problems such as durability,
      lifetime, high process temperature, and difficulty in controlling the morphology
      of nanostructures. Here, we report a facile method to fabricate monolithic
      nanoporous In-Sn alloy, a network of nanopores, induced by electroreduction of
      indium tin oxide nanobranches (ITO BRs). The electroreduction process
      concentrated a local electric field at the tip of the nanostructure, leading to
      current-assisted joule-heating to form a nanoporous In-Sn alloy. Scanning
      electron microscopy images showed that the nanopore size of In-Sn alloy could be
      controlled from 1176 to 65 nm by tuning the electroreduction condition: the
      applied potential and the time. As a result, formate Faradaic efficiency could be
      improved from 42.4% to 78.6%. Also, current density was increased from -6.6 to 
      9.6 mA/cm2 at -1.2 VRHE, thereby resulting in the highest HCOO- production rate
      of 75.9 MUmol/(h cm2). Detachment of catalysts from the substrate was not
      observed even after a long-term (12 h) electrochemical measurement at high
      potential (-1.2 VRHE). This work provides a design rule to fabricate highly
      efficient and stable oxide-derived electrocatalysts.

PMID- 29220160
TI  - Plant Protein-Directed Synthesis of Luminescent Gold Nanocluster Hybrids for
      Tumor Imaging.
AB  - Nowadays, fluorescence detection has emerged as one of the most frequently used
      noninvasive biosensing methods to selectively monitor biological processes within
      living systems. Among fluorescent nanoparticles (NPs), gold nanoclusters (AuNCs)
      have been intensively studied because of their intrinsic fluorescence and their
      endowed biocompatible surface. Herein, we selected an abundant, low-cost, and
      sustainable plant protein, the pea protein isolate (PPI), for its excellent
      biocompatibility, biodegradability, and nonallergenic character to be employed as
      both a reducing and stabilizing agent to facilely produce AuNCs exhibiting a
      strong red fluorescence. Afterward, the formed AuNCs/PPI mixture was able to self
      assemble into NPs (AuNCs/PPI NPs) with the size of about 100 nm simply through a
      dialyzing process. Taking advantage from the protein nature of PPI, AuNCs/PPI NPs
      demonstrate both excellent biocompatibility and colloidal stability. Moreover,
      AuNCs/PPI NPs showed a great capability when employed as a bioimaging probe for
      both in vitro and in vivo imaging. Finally, AuNCs/PPI NPs were coated with red
      blood cell (RBC) membranes to improve their blood circulation property and
      enhance their tumor enrichment ability to meet the requirement for practical use.
      Results convincingly show that such super NPs (RBC-coated AuNCs/PPI NPs) were
      able to successfully locate tumor in vivowith an excellent imaging capability,
      which provides a new strategy for bioimaging with fluorescent NPs.

PMID- 29220161
TI  - Sequential Migrations between Boron and Rhodium Centers: A Cooperative Process
      between Rhodium and a Monosubstituted Borohydride Unit.
AB  - The sodium salt of a monosubstituted borohydride anion containing a 2
      mercaptopyridyl unit (mp) is reported herein. This compound was coordinated to a
      rhodium(I) center providing the complex [Rh{kappa3-H,H,S-H3B(mp)}(NBD)] (1)
      (where NBD = 2,5-norbornadiene) in which the boron-based ligand is coordinated to
      the rhodium center via the thione donor and two of the B-H bonds of the BH3 unit.
      Reaction of complex 1 with carbon monoxide results in the activation of the
      complex leading to the product of a formal intramolecular hydroboration reaction,
      where the NBD unit has, in effect, inserted into one of the B-H bonds. Three
      complexes were prepared in which the newly formed norbornenyl unit (nbe) is
      located at the boron center, namely, [Rh{kappa3-H,H,S-H2B(nbe)(mp)}(CO)2] (2),
      [Rh{kappa3-H,H,S-H2B(nbe)(mp)}(CO)(PCy3)] (3), and [Rh{kappa3-H,H,S
      H2B(nbe)(mp)}(CO)(PPh3)] (4). The identities of the three complexes were
      confirmed by spectroscopic and analytical techniques. Further confirmation was
      obtained via structural characterization of 3. Studies confirmed that the
      reactivity occurs at the metal center. A metal-ligand cooperative mechanism,
      involving initial migration of hydride from boron to metal center, was postulated
      for the formation of the new complexes based on previous investigations. The
      newly formed norbornenyl unit then migrates from metal center to boron.

PMID- 29220162
TI  - Albumin-Assisted Synthesis of Ultrasmall FeS2 Nanodots for Imaging-Guided
      Photothermal Enhanced Photodynamic Therapy.
AB  - Current mainstream cancer treatment methods have their limitations. New
      approaches are thus desired to assist our battle against cancer. Herein,
      multifunctional ultrasmall FeS2 nanodots with the size of 7 nm are synthesized by
      biomineralization and used for imaging-guided combined tumor therapy. Bovine
      serum albumin (BSA), which acts as the reaction template to induce the
      mineralization of FeS2 nanomaterials under alkaline conditions, could also be
      used as a drug delivery system for coupling photosensitive molecule such as
      Chlorin e6 (Ce6). Taking advantage of the near-infrared (NIR) absorbance and the
      high r2 relaxivity of the synthesized ultrasmall FeS2 nanodots, as well as the
      Ce6 fluorescence, in vivo trimodal imaging of optical/magnetic
      resonance/photoacoustics was carried out, showing efficient tumor accumulation of
      FeS2@BSA-Ce6 after intravenous injection. In vitro and in vivo photothermal and
      photodynamic therapy were then conducted for synergistic tumor therapy and did
      not cause any apparent toxicity to the treated animals. Our work thus provides a
      new kind of ultrasmall FeS2 multifunctional nanodot modified by albumin via a
      simple method, promising for combination phototherapy as well as cancer
      theranostics.

PMID- 29220163
TI  - Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New
      Platform for Lipid Isomer Analyses.
AB  - One of the most significant challenges in contemporary lipidomics lies in the
      separation and identification of lipid isomers that differ only in site(s) of
      unsaturation or geometric configuration of the carbon-carbon double bonds. While
      analytical separation techniques including ion mobility spectrometry (IMS) and
      liquid chromatography (LC) can separate isomeric lipids under appropriate
      conditions, conventional tandem mass spectrometry cannot provide unequivocal
      identification. To address this challenge, we have implemented ozone-induced
      dissociation (OzID) in-line with LC, IMS, and high resolution mass spectrometry.
      Modification of an IMS-capable quadrupole time-of-flight mass spectrometer was
      undertaken to allow the introduction of ozone into the high-pressure trapping ion
      funnel region preceding the IMS cell. This enabled the novel LC-OzID-IMS-MS
      configuration where ozonolysis of ionized lipids occurred rapidly (10 ms) without
      prior mass-selection. LC-elution time alignment combined with accurate mass and
      arrival time extraction of ozonolysis products facilitated correlation of
      precursor and product ions without mass-selection (and associated reductions in
      duty cycle). Unsaturated lipids across 11 classes were examined using this
      workflow in both positive and negative ion modalities, and in all cases, the
      positions of carbon-carbon double bonds were unequivocally assigned based on
      predictable OzID transitions. Under these conditions, geometric isomers exhibited
      different IMS arrival time distributions and distinct OzID product ion ratios
      providing a means for discrimination of cis/trans double bonds in complex lipids.
      The combination of OzID with multidimensional separations shows significant
      promise for facile profiling of unsaturation patterns within complex lipidomes
      including human plasma.

PMID- 29220164
TI  - Ambidextrous Chirality Transfer Capability from Cellulose Tris(phenylcarbamate)
      to Nonhelical Chainlike Luminophores: Achiral Solvent-Driven Helix-Helix
      Transition of Oligo- and Polyfluorenes Revealed by Sign Inversion of Circularly
      Polarized Luminescence and Circular Dichroism Spectra.
AB  - We investigated whether helicity and/or chirality of cellulose
      tris(phenylcarbamate) (CTPC) can transfer to noncharged, nonhelical oligo- and
      polyfluorenes when CTPC was employed as a solution processable homochiral
      platform of a D-glucose-skeletal polymer. Noticeably, CTPC revealed the solvent
      driven, ambidextrous intermolecular helicity/chirality transfer capability to
      these fluorenes. The chiroptical inversion characteristics of circularly
      polarized luminescence (CPL) and the corresponding CD spectra were realized by
      solely choosing a proper achiral solvent and/or achiral cosolvent. When the
      solution of PF6 and CTPC in tetrahydrofuran (THF) was cast on a quartz substrate,
      the dissymmetry ratio of CPL (gCPL) from the polymer film showed gCPL = +2.1 * 10
      3 at 429 nm. Conversely, when dichloromethane (DCM) was used as the solvent, the
      CPL sign was inverted to gCPL = -2.4 * 10-3 at 429 nm. The dissymmetry ratio of
      Cotton CD band (gCD) from the THF solution was gCD = +3.2 * 10-3 at 392 nm;
      conversely, from the DCM, the CD sign inverted to gCD = -0.8 * 10-3 at 371 nm.
      The sign and magnitude of the gCD values were interpreted to a London dispersion
      term (deltad) of Hansen solubility parameter (delta) of the casting solvents
      rather than a dipole-dipole interaction term (deltap) and a hydrogen bonding
      interaction term (deltah) of the delta values and dielectric constant (epsilon).
      Analysis of solvent-driven changes in FTIR spectra, wide-angle X-ray diffraction
      profiles, and differential scanning calorimetry diagrams indicated that solvent
      driven on-off switching of multiple hydrogen bonds due to three urethane groups
      of CTPC play the key for the inversion. Intermolecular CH/pi and pi-pi
      interactions among phenyl rings and alkyl groups were assumed to be crucial for
      helicity/chirality transfer capability based on molecular mechanics and molecular
      dynamics simulations of PF6-CTPC hybrids. These chiroptical inversion
      characteristics arose from solvent-driven order-disorder transition
      characteristics of the CTPC helix rather than a helix-helix transition of CTPC
      itself.

PMID- 29220165
TI  - Phototriggered N2-Generating Submicron Particles for Selective Killing of Cancer
      Cells.
AB  - Killing of cancer cells by applying mechanical disruption has been an appealing
      emerging strategy for cancer treatment in recent years. In this study,
      photoresponsive submicron particles based on diazo-resin that are able to release
      N2 under UV irradiation were prepared through a polyamine-salt aggregation
      method. After surface modification with hyaluronic acid, the particles could be
      internalized selectively by cancer cells and were mainly located in lysosomes
      after 6 h incubation. The viability of cancer cells decreased obviously after
      they were co-cultured with photoresponsive particles and UV irradiation due to
      the integrity damage of lysosomes by phototriggered N2 generation and the
      subsequent increased number of reactive oxygen species.

PMID- 29220166
TI  - Electrochemistry of Ruthenium Bis(imino)pyridine Compounds: Evidence for an ECE
      Mechanism and Isolation of Mono and Dicationic Complexes.
AB  - The electrochemical properties of a series of ruthenium complexes bearing the
      redox noninnocent bis(imino)pyridine ligand were investigated with cyclic
      voltammetry. An unexpected electrochemical feature in one of the complexes
      indicated a possible electrochemical-chemical-electrochemical (ECE) process.
      Further investigation into the oxidation mechanism included the synthesis and
      isolation of cationic and dicationic analogues of the complex. Density functional
      theory calculations suggested that a solvent interaction facilitated the ECE
      mechanism, so a solvent adduct was also synthesized and isolated. Calculations of
      this series of compounds were used to investigate the stabilizing role of the
      ligands over various oxidation states. As the overall charge of the complex was
      varied from anion to dication, a relatively constant Ru metal center oxidation
      state was found over all four states probed. This result suggests the strong
      involvement of the coligands in the redox behavior of the complexes investigated.

PMID- 29220167
TI  - Computational Systems Biochemistry: Beyond the Static Interactome.

PMID- 29220168
TI  - Hybrid Structure of 2D Layered GaTe with Au Nanoparticles for Ultrasensitive
      Detection of Aromatic Molecules.
AB  - Owing to a complex monocline structure and high-density of defects in
      monocrystalline GaTe, the performance of GaTe-based electronic devices is
      considerably compromised. Yet, the defects' nature in GaTe could be a merit
      rather than a shortcoming in other realms. In our work, the density of defects in
      GaTe films is utilized for a facile decoration of Au nanoparticles (NPs), which
      allowed us to extend its application potential to the domain of surface enhanced
      Raman scattering (SERS) for the first time. Two-dimensional (2D) GaTe layered
      structures are prepared by mechanical exfoliation, and high-density Au NPs are
      synthesized by immersion of 2D GaTe in HAuCl4 aqueous solution. By varying the
      immersion time, the sizes and coverage rate of Au NPs on GaTe can be elaborately
      tuned. Thanks to the defect nature of GaTe, the maximum coverage amounts to 98%.
      The hereby achieved Au-NPs-2D-GaTe hybrid structure demonstrates outstanding
      properties as a superior SERS substrate for ultrasensitive detection of R6G
      aromatic molecules. Remarkably, the enhancement factor reaches up to 1.6 * 104,
      and the minimum detectable concentration is 10-11 M, undercutting that of
      recently reported Au-NPs-MoS2 SERS and Au-NPs-graphene SERS substrates which have
      a similar structure. With superior detection capability and facile preparation,
      Au-NPs-GaTe SERS substrates can become a perfect choice for the detection of
      aromatic molecules.

PMID- 29220169
TI  - Sb Nanoparticles Anchored on Nitrogen-Doped Amorphous Carbon-Coated Ultrathin
      CoSx Nanosheets for Excellent Performance in Lithium-Ion Batteries.
AB  - Compared to single-component materials, hybrid materials with various components
      display superior electrochemical performance. In this work, two-dimensional
      CoSx@NC@Sb nanosheets assembled by ultrathin CoSx nanosheets (~4 nm) and a thin
      layer of N-doped amorphous carbon (NC) combined with colloidlike Sb nanoparticles
      are designed and synthesized via a solvothermal route accompanied by a
      carbonization and Sb deposition procedure. If applied in lithium-ion batteries
      (LIBs), the hybrids exhibit a specific capacity of 960 mA h g-1 at the 100th
      cycle at 0.1 A g-1. Moreover, the reversible capacity still maintains at 494 mA h
      g-1 after 500 cycles at a high rate of 10 A g-1. All enhanced electrochemical
      properties of the hybrids are attributed to the synergistic effect of the two
      components and their unique structural features, which can effectively increase
      the electrical conductivity, shorten the pathway of Li+ diffusion, accommodate
      the volume variation, and inhibit the aggregation and pulverization of the
      electrode. We believe that the current work can provide a new strategy for
      designing and fabricating high-performance anode materials for LIBs.

PMID- 29220170
TI  - Sustainable Conversion of Carbon Dioxide: An Integrated Review of Catalysis and
      Life Cycle Assessment.
AB  - CO2 conversion covers a wide range of possible application areas from fuels to
      bulk and commodity chemicals and even to specialty products with biological
      activity such as pharmaceuticals. In the present review, we discuss selected
      examples in these areas in a combined analysis of the state-of-the-art of
      synthetic methodologies and processes with their life cycle assessment. Thereby,
      we attempted to assess the potential to reduce the environmental footprint in
      these application fields relative to the current petrochemical value chain. This
      analysis and discussion differs significantly from a viewpoint on CO2 utilization
      as a measure for global CO2 mitigation. Whereas the latter focuses on reducing
      the end-of-pipe problem "CO2 emissions" from todays' industries, the approach
      taken here tries to identify opportunities by exploiting a novel feedstock that
      avoids the utilization of fossil resource in transition toward more sustainable
      future production. Thus, the motivation to develop CO2-based chemistry does not
      depend primarily on the absolute amount of CO2 emissions that can be remediated
      by a single technology. Rather, CO2-based chemistry is stimulated by the
      significance of the relative improvement in carbon balance and other critical
      factors defining the environmental impact of chemical production in all relevant
      sectors in accord with the principles of green chemistry.

PMID- 29220171
TI  - Exothermic or Endothermic Decomposition of Disubstituted Tetrazoles Tuned by
      Substitution Fashion and Substituents.
AB  - Nitrogen-rich compounds such as tetrazoles are widely used as candidates in gas
      generating agents. However, the details of the differentiation of the two isomers
      of disubstituted tetrazoles are rarely studied, which is very important
      information for designing advanced materials based on tetrazoles. In this
      article, pairs of 2,5- and 1,5-disubstituted tetrazoles were carefully designed
      and prepared for study on their thermal decomposition behavior. Also, the
      substitution fashion of 2,5- and 1,5- and the substituents at C-5 position were
      found to affect the endothermic or exothermic properties. This is for the first
      time to the best of our knowledge that the thermal decomposition properties of
      different tetrazoles could be tuned by substitution ways and substitute groups,
      which could be used as a useful platform to design advanced materials for
      temperature-dependent rockets. The aza-Claisen rearrangement was proposed to
      understand the endothermic decomposition behavior.

PMID- 29220172
TI  - Experimental Evidence for Noncanonical Thymine Cation Radicals in the Gas Phase.
AB  - Thymine cation radicals were generated in the gas phase by collision-induced
      intramolecular electron transfer in [Cu(2,2':6,2"-terpyridine)(thymine)]2+*
      complexes and characterized by ion-molecule reactions, UV-vis photodissociation
      action spectroscopy, and ab initio and density functional theory calculations.
      The experimental results indicated the formation of a tautomer mixture consisting
      chiefly (77%) of noncanonical tautomers with a C-7-H2 group. The canonical 2,4
      dioxo-N-1,N-3-H isomer was formed as a minor component at ca. 23%. Ab initio
      CCSD(T) calculations indicated that the canonical [thymine]+* ion was not the
      lowest-energy isomer. This contrasts with neutral thymine, for which the
      canonical isomer is the lowest-energy structure. Exothermic unimolecular
      isomerization by a methyl hydrogen migration in the canonical [thymine]+* ion
      required a low energy barrier, forming a C-7-H2,O-4-H isomer. Noncanonical
      thymine tautomers with a C-7-H2 group were also identified by calculations as low
      energy isomers of 2'-deoxythymidine phosphate cation radicals. The relative
      energies of thymidine ion isomers were sensitive to the computational method used
      and were affected by solvation. The noncanonical [thymine]+* ions have extremely
      low adiabatic recombination energies (REadiab < 5.9 eV), making them potential
      ionization hole traps in ionized nucleic acids.

PMID- 29220173
TI  - Use of Reconstitued Yolk Systems To Study the Gelation Mechanism of Frozen-Thawed
      Hen Egg Yolk.
AB  - Yolk gelation upon 5 week freezing-thawing was studied in four recombined yolk
      systems containing different plasma and granule proportions. Fractionation for
      mass distribution, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) for protein distribution, and rheological properties were explored. Results
      indicate that both plasma and granule components, including low-density
      lipoprotein (LDL), high-density lipoprotein (HDL), and alpha-livetin proteins,
      contributed to gelation. Protein aggregation was reflected through a large mass
      increase in the granule fraction and appearance of a floating LDL layer upon
      fractionation of gelated yolk systems. A significant increase in gel strength
      (elastic modulus, G') was observed with the increase of the granule content.
      Overall, this study provides a better understanding of yolk gelation mechanism
      that may consequently lead to the design of innovative methods for preventing
      gelation. A schematic presentation of the yolk gelation mechanism is also
      proposed.

PMID- 29220174
TI  - Intramolecular HB Interactions Evidenced in Dibenzoyl Oxalamide Derivatives: NMR,
      QTAIM, and NCI Studies.
AB  - Extensive NMR spectroscopic studies revealed information on the occurrence of
      bifurcated intramolecular hydrogen bond in the dibenzoyl oxalamide derivatives.
      One-dimensional NMR experiments, viz., solvent dilution, temperature
      perturbation, and two-dimensional experimental techniques, such as 15N-1H HSQC
      and 19F-1H HOESY, have been exploited to derive unambiguous confirmation of the
      participation of organic fluorine in the hydrogen-bonding interaction. The
      experimental NMR findings have been ratified by density functional theory based
      calculations, viz., NCI (noncovalent interaction) and QTAIM (quantum theory of
      atoms in molecules).

PMID- 29220177
TI  - (+)-Methyl (1R,2S)-2-{[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1
      phenylcyclopropanecarboxylate [(+)-MR200] Derivatives as Potent and Selective
      Sigma Receptor Ligands: Stereochemistry and Pharmacological Properties.
AB  - Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis
      (+)-MR200], cis-(-)-1a [cis-(-)-MR201], and trans-(+/-)-1a [trans-(+/-)-MR204],
      have been identified as new potent sigma (sigma) receptor ligands. In the present
      paper, novel enantiomerically pure analogues were synthesized and optimized for
      their sigma receptor affinity and selectivity. Docking studies rationalized the
      results obtained in the radioligand binding assay. Absolute stereochemistry was
      unequivocally established by X-ray analysis of precursor trans-(+)-5a as
      camphorsulfonyl derivative 9. The most promising compound, trans-(+)-1d, showed
      remarkable selectivity over a panel of more than 15 receptors as well as good
      chemical and enzymatic stability in human plasma. An in vivo evaluation evidenced
      that trans-(+)-1d, in contrast to trans-(-)-1d, cis-(+)-1d, or cis-(-)-1d, which
      behave as sigma1 antagonists, exhibited a sigma1 agonist profile. These data
      clearly demonstrated that compound trans-(+)-1d, due to its sigma1 agonist
      activity and favorable receptor selectivity and stability, provided an useful
      tool for the study of sigma1 receptors.

PMID- 29220176
TI  - Highly Efficient Erythritol Recovery from Waste Erythritol Mother Liquor by a
      Yeast-Mediated Biorefinery Process.
AB  - Erythritol, a natural sugar alcohol, is produced industrially by fermentation and
      crystallization, but this process leaves a large amount of waste erythritol
      mother liquor (WEML) which contains more than 200 g/L erythritol as well as other
      polyol byproducts. These impurities make it very difficult to crystallize more
      erythritol. In our study, an efficient process for the recovery of erythritol
      from the WEML is described. The polyol impurities were first identified by high
      performance liquid chromatography and gas chromatography-mass spectrometry, and a
      yeast strain Candida maltosa CGMCC 7323 was then isolated to metabolize those
      impurities to purify erythritol. Our results demonstrated that the process could
      remarkably improve the purity of erythritol and thus make the subsequent
      crystallization easier. This newly developed strategy is expected to have
      advantages in WEML treatment and provide helpful information with regard to green
      cell factories and zero-waste processing.

PMID- 29220178
TI  - Equilibrium between a Droplet and Surrounding Vapor: A Discussion of Finite Size
      Effects.
AB  - In a theoretical description of homogeneous nucleation one frequently assumes an
      "equilibrium" coexistence of a liquid droplet with surrounding vapor of a density
      exceeding that of a saturated vapor at bulk vapor-liquid two-phase coexistence.
      Thereby one ignores the caveat that in the thermodynamic limit, for which the
      vapor would be called supersaturated, such states will at best be metastable with
      finite lifetime, and thus not be well-defined within equilibrium statistical
      mechanics. In contrast, in a system of finite volume stable equilibrium
      coexistence of droplet and supersaturated vapor at constant total density is
      perfectly possible, and numerical analysis of equilibrium free energies of finite
      systems allows to obtain physically relevant results. In particular, such an
      analysis can be used to derive the dependence of the droplet surface tension
      gamma( R) on the droplet radius R by computer simulations. Unfortunately,
      however, the precision of the results produced by this approach turns out to be
      seriously affected by a hitherto unexplained spurious dependence of gamma( R) on
      the total volume V of the simulation box. These finite size effects are studied
      here for the standard Ising/lattice gas model in d = 2 dimensions and an Ising
      model on the face-centered cubic lattice with 3-spin interaction, lacking
      symmetry between vapor and liquid phases. There also the analogous case of
      bubbles surrounded by undersaturated liquid is treated. It is argued that (at
      least a large part of) the finite size effects result from the translation
      entropy of the droplet or bubble in the system. This effect has been shown
      earlier to occur also for planar interfaces for simulations in the slab geometry.
      Consequences for the estimation of the Tolman length are briefly discussed. In
      particular, we find clear evidence that in d = 2 the leading correction of the
      curvature-dependent interface tension is a logarithmic term, compatible with
      theoretical expectations, and we show that then the standard Tolman-style
      analysis is inapplicable.

PMID- 29220175
TI  - Spectroscopic Signature for Stable beta-Amyloid Fibrils versus beta-Sheet-Rich
      Oligomers.
AB  - We use two-dimensional IR (2D IR) spectroscopy to explore fibril formation for
      the two predominant isoforms of the beta-amyloid (Abeta1-40 and Abeta1-42)
      protein associated with Alzheimer's disease. Two-dimensional IR spectra resolve a
      transition at 1610 cm-1 in Abeta fibrils that does not appear in other Abeta
      aggregates, even those with predominantly beta-sheet-structure-like oligomers.
      This transition is not resolved in linear IR spectroscopy because it lies under
      the broad band centered at 1625 cm-1, which is the traditional infrared signature
      for amyloid fibrils. The feature is prominent in 2D IR spectra because 2D
      lineshapes are narrower and scale nonlinearly with transition dipole strengths.
      Transmission electron microscopy measurements demonstrate that the 1610 cm-1 band
      is a positive identification of amyloid fibrils. Sodium dodecyl sulfate micelles
      that solubilize and disaggregate preaggregated Abeta samples deplete the 1625 cm
      1 band but do not affect the 1610 cm-1 band, demonstrating that the 1610 cm-1
      band is due to very stable fibrils. We demonstrate that the 1610 cm-1 transition
      arises from amide I modes by mutating out the only side-chain residue that could
      give rise to this transition, and we explore the potential structural origins of
      the transition by simulating 2D IR spectra based on Abeta crystal structures. It
      was not previously possible to distinguish stable Abeta fibrils from the less
      stable beta-sheet-rich oligomers with infrared light. This 2D IR signature will
      be useful for Alzheimer's research on Abeta aggregation, fibril formation, and
      toxicity.

PMID- 29220179
TI  - Stabilization of Saturated Carbocations in Condensed Phases.
AB  - Based on the experimentally established mechanism of hyperconjugative
      stabilization of the simplest saturated carbocations [Stoyanov, E. S.; et al.
      PCCP, 2017, 19, 7270], the infrared spectra of t-alkyl+ and methyl-cyclo-pentyl+
      carbocations were interpreted. This approach allows us to extract new information
      about the electronic state of (CH3)2C+R cations with R = H, CH3, C2H5, C4H7, and
      CH(CH3)2, namely, the electron density distribution over the (CH3)2C group and
      the positive charge dispersion on the H atoms of this group. Thus, donation of
      the electron density to the empty 2pz orbital of the sp2 C atom occurs not only
      from one C-H bond oriented parallel to the 2pz orbital but also equally from all
      other C-H and C-C bonds of the molecular group involved in hyperconjugation. This
      mechanism preserved the isoelectronic nature of this group toward the
      corresponding groups of the neutral alkanes. Hyperconjugation and polarization
      are closely linked in stabilization of carbocations: the strengthening of one
      effect weakens the second and vice versa without changing the efficiency of
      scattering of the positive charge in the carbocation. In the condensed phase,
      carbocations are additionally stabilized by the bulk effect and hydrogen bonding
      with the environment: increasing H-bonding strength increased hyperconjugation
      and decreased polarization. The contribution of all the effects on the
      stabilization of carbocations was evaluated.

PMID- 29220180
TI  - Securamine Derivatives from the Arctic Bryozoan Securiflustra securifrons.
AB  - Bryozoans belonging to the Flustridae family have proven to be a rich source of
      structurally unique secondary metabolites. As part of our continuing search for
      bioactive secondary metabolites from Arctic marine invertebrates, the organic
      extract of Securiflustra securifrons was examined. This resulted in the isolation
      of three new halogenated, hexacyclic indole-imidazole alkaloids, securamines H-J
      (1-3), together with the previously reported compounds securamines C (4) and E
      (5). The structures of the new compounds were elucidated by spectroscopic methods
      including 1D and 2D NMR and analysis of HRMS data. Through NMR and HRMS analysis,
      we were also able to prove that 1, 2, 4, and 5, when dissolved in MeOH, were
      converted into their corresponding artifacts, the securamine MeOH adducts m1, m2,
      m4, and m5. When redissolved in a non-nucleophilic solvent, the native variants
      were re-formed. We also found that 3 was a MeOH addition product of a native
      variant. Even though the structures of several securamines have been reported,
      their bioactivities were not examined. The securamines displayed various degrees
      of cytotoxicity against the human cancer cell lines A2058 (skin), HT-29 (colon),
      and MCF-7 (breast), as well as against nonmalignant human MRC-5 lung fibroblasts.
      Compounds 1, 2, and 5 were found to be active, with IC50 values against the
      cancer cell lines ranging from 1.4 +/- 0.1 to 10 +/- 1 MUM. The cytotoxicity of 1
      was further evaluated and found to be time-dependent.

PMID- 29220181
TI  - N-Hydroxyphthalimide-Mediated Electrochemical Iodination of Methylarenes and
      Comparison to Electron-Transfer-Initiated C-H Functionalization.
AB  - An electrochemical method has been developed for selective benzylic iodination of
      methylarenes. The reactions feature the first use of N-hydroxyphthalimide as an
      electrochemical mediator for C-H oxidation to nonoxygenated products. The method
      provides the basis for direct (in situ) or sequential benzylation of diverse
      nucleophiles using methylarenes as the alkylating agent. The hydrogen-atom
      transfer mechanism for C-H iodination allows C-H oxidation to proceed with
      minimal dependence on the substrate electronic properties and at electrode
      potentials 0.5-1.2 V lower than that of direct electrochemical C-H oxidation.

PMID- 29220182
TI  - Total Synthesis of Reniochalistatin E.
AB  - Reniochalistatin E (1) is one of the five related cyclic peptides isolated from
      the marine sponge Reniochalina stalagmitis. The discovery of these compounds
      resulted from a screening program directed toward the identification of proline
      rich bioactive compounds. Reniochalistatin E is the only member of the family to
      possess a tryptophan amino acid residue. Given the cytotoxicity observed for 1,
      efforts were directed toward developing a synthetic route to 1. The first total
      synthesis of 1 has been accomplished in a 15-step route in an overall 5.0% yield.
      The synthetic sample of reniochalistatin E was shown to have similar activity
      toward HeLa and RPMI-8226 cell lines compared to the natural sample, with IC50
      values of 16.9 vs 17.3 MUM and 4.5 vs 4.9 MUM, respectively. Interestingly, both
      of the fully deprotected octapeptides constructed toward the synthesis of
      reniochalistatin E were shown to have cytotoxicity. The route provides a means to
      probe the structure-activity relationship of 1 and further biological
      investigations.

PMID- 29220183
TI  - Catalytic Nucleophilic Allylation Driven by the Water-Gas Shift Reaction.
AB  - The ruthenium-catalyzed allylation of aldehydes with allylic pro-nucleophiles has
      been demonstrated to be an efficient means to form carbon-carbon bonds under mild
      conditions. The evolution of this reaction from the initial serendipitous
      discovery to its general synthetic scope is detailed, highlighting the roles of
      water, CO, and amine in the generation of a more complete catalytic cycle. The
      use of unsymmetrical allylic pro-nucleophiles was shown to give preferential
      product formation through the modulation of reaction conditions. Both (E)
      cinnamyl acetate and vinyl oxirane were efficiently used to form the anti
      branched products (up to >20:1 anti/syn) and E-linear products (up to >20:1 E/Z)
      in high selectivity with aromatic, alpha,beta-unsaturated, and aliphatic
      aldehydes, respectively. Attempts to render the reaction enantioselective are
      highlighted and include enantioenrichment of up to 75:25 for benzaldehyde.

PMID- 29220184
TI  - Matrix-Isolation and Quantum-Chemical Analysis of the C3v Conformer of XeF6,
      XeOF4, and Their Acetonitrile Adducts.
AB  - A joint experimental-computational study of the molecular structure and
      vibrational spectra of the XeF6 molecule is reported. The vibrational
      frequencies, intensities, and in particular the isotopic frequency shifts of the
      vibrational spectra for 129XeF6 and 136XeF6 isotopologues recorded in the neon
      matrix agree very well with those obtained from relativistic coupled-cluster
      calculations for XeF6 in the C3v structure, thereby strongly supporting the
      observation of the C3v conformer of the XeF6 molecule in the neon matrix. A C3v
      transition state connecting the C3v and Oh local minima is located
      computationally. The calculated barrier of 220 cm-1 between the C3v minima and
      the transition state corroborates the experimental observation of the C3v
      conformer and the absence of the Oh conformer in solid noble gas matrices. For
      comparison matrix-isolation spectra have also been recorded and analyzed for the
      129XeOF4 and the 136XeOF4 isotopologues. The matrix-isolation complexation shifts
      obtained for the XeF6.NCCH3 relative to those of free matrix isolated XeF6 and
      CH3CN are in good agreement with those reported for crystalline XeF6.NCCH3.

PMID- 29220185
TI  - Regioselective Synthesis of Bicyclic and Polycyclic Systems by Cycloaddition
      Reactions of Alkenyl p-Benzoquinones.
AB  - An efficient [3 + 2]/[4 + 2] or double [4 + 2] cycloaddition strategy has been
      established for the synthesis of heterocyclic systems under mild conditions. The
      reaction pathway is governed by the nature of reaction partner. Several
      dihydrofurocoumarin, furopyranocoumarin, dihydrofuran, dihydrobenzopyran, and
      dihydrobenzofuran derivatives were obtained as single diastereomers from cyclic
      or acyclic enol ethers and styrenes. This one-pot transformation constructed C-C
      and C-O bonds and generated molecular complexity by domino/tandem process to
      produce the heterocyclic systems in good yields. The ring closure of domino
      protocol was highly stereoselective and resulted in the formation of cis-fused
      systems.

PMID- 29220186
TI  - Detection of CO2*- in the Electrochemical Reduction of Carbon Dioxide in N,N
      Dimethylformamide by Scanning Electrochemical Microscopy.
AB  - The electrocatalytic reduction of CO2 has been studied extensively and produces a
      number of products. The initial reaction in the CO2 reduction is often taken to
      be the 1e formation of the radical anion, CO2*-. However, the electrochemical
      detection and characterization of CO2*- is challenging because of the short
      lifetime of CO2*-, which can dimerize and react with proton donors and even mild
      oxidants. Here, we report the generation and quantitative determination of CO2*-
      in N,N-dimethylformamide (DMF) with the tip generation/substrate collection
      (TG/SC) mode of scanning electrochemical microscopy (SECM). CO2 was reduced at a
      hemisphere-shaped Hg/Pt ultramicroelectrode (UME) or a Hg/Au film UME, which were
      utilized as the SECM tips. The CO2*- produced can either dimerize to form oxalate
      within the nanogap between SECM tip and substrate or collected at SECM substrate
      (e.g., an Au UME). The collection efficiency (CE) for CO2*- depends on the
      distance (d) between the tip and substrate. The dimerization rate (6.0 * 108 M-1
      s-1) and half-life (10 ns) of CO2*- can be evaluated by fitting the collection
      efficiency vs distance curve. The dimerized species of CO2*-, oxalate, can also
      be determined quantitatively. Furthermore, the formal potential (E0') and
      heterogeneous rate constant (k0) for CO2 reduction were determined with different
      quaternary ammonium electrolytes. The significant difference in k0 is due to a
      tunneling effect caused by the adsorption of the electrolytes on the electrode
      surface at negative potentials.

PMID- 29220187
TI  - Oscillatory Magnetic Circular Dichroism of Free-Carrier Absorption and
      Determination of the Rashba Dispersions in Hybrid Organic-Inorganic Perovskites.
AB  - Free-carrier absorption (FCA) in a semiconductor provides information about the
      band on which the free carriers reside, and in the classical limit, follows the
      omega-2 law with omega being the photon frequency. In hybrid organic-inorganic
      perovskites (HOIPs), the colossal Rashba effect (RE) results in a new band
      dispersion, characterized by wavevector |k| = k0 of band extremum and effective
      mass m*. Here we show that the colossal RE in two-dimensional HOIPs greatly
      enhances phonon-assisted FCA with a modified frequency dependence and induces a
      direct transition between the subbands with a resonance at homega = 4R =
      2h2k02/m*, which, under a magnetic field, exhibits a strong oscillatory magnetic
      circular dichroism (MCD). The MCD spectrum allows a complete and reliable
      determination of k0 and m* for conduction and valence bands in HOIPs and helps
      reveal the microscopic mechanism of their outstanding photovoltaic performance.

PMID- 29220188
TI  - Instability Mechanisms of Water-in-Oil Nanoemulsions with Phospholipids: Temporal
      and Morphological Structures.
AB  - Many food preparations, pharmaceuticals, and cosmetics use water-in-oil (W/O)
      emulsions stabilized by phospholipids. Moreover, recent technological
      developments try to produce liposomes or lipid coated capsules from W/O
      emulsions, but are faced with colloidal instabilities. To explore these
      instability mechanisms, emulsification by sonication was applied in three cycles,
      and the sample stability was studied for 3 h after each cycle. Clearly
      identifiable temporal structures of instability provide evidence about the
      emulsion morphology: an initial regime of about 10 min is shown to be governed by
      coalescence after which Ostwald ripening dominates. Transport via molecular
      diffusion in Ostwald ripening is commonly based on the mutual solubility of the
      two phases and is therefore prohibited in emulsions composed of immiscible
      phases. However, in the case of water in oil emulsified by phospholipids, these
      form water-loaded reverse micelles in oil, which enable Ostwald ripening despite
      the low solubility of water in oil, as is shown for squalene. As is proved for
      the phospholipid dipalmitoylphosphatidylcholine (DPPC), concentrations below the
      critical aggregation concentration (CAC) form monolayers at the interfaces and
      smaller droplet sizes. In contrast, phospholipid concentrations above the CAC
      create complex multilayers at the interface with larger droplet sizes. The key
      factors for stable W/O emulsions in classical or innovative applications are
      first, the minimization of the phospholipids' capacity to form reversed micelles,
      and second, the adaption of the initial phospholipid concentration to the water
      content to enable an optimized coverage of phospholipids at the interfaces for
      the intended drop size.

PMID- 29220189
TI  - Plasmon-Induced Ultrafast Hydrogen Production in Liquid Water.
AB  - Hydrogen gas production from solar water splitting provides a renewable energy
      cycle to address the grand global energy challenge; however, its dynamics and
      fundamental mechanism remain elusive. We directly explore by first-principles the
      ultrafast electron-nuclear quantum dynamics on the time scale of ~100 fs during
      water photosplitting on a plasmonic cluster embedded in liquid water. Water
      molecule splitting is assisted by rapid proton transport in liquid water in a
      Grotthuss-like mechanism. We identify that a plasmon-induced field enhancement
      effect dominates water splitting, while charge transfer from gold to the
      antibonding orbital of a water molecule also plays an important role. "Chain
      reaction" like rapid H2 production is observed via the combination of two
      hydrogen atoms from different water molecules. These results provide a route
      toward a complete understanding of water photosplitting in the ultimate time and
      spatial limit.

PMID- 29220190
TI  - A Total Synthesis of the Antifungal Deoxyaminocyclitol Nabscessin B from l-(+)
      Tartaric Acid.
AB  - Aminocyclitol 2, a recently isolated and notable antifungal agent, was prepared
      from homochiral gamma-hydroxycyclohexenone 4, which is itself available in six
      steps from l-(+)-tartaric acid (3). The well-defined rigidifying effect arising
      from the 1,2-diacetal protecting group associated with compound 4 and its
      derivatives allows for high levels of regio- and stereo-chemical control in the
      manipulation of the cyclitol framework.

PMID- 29220191
TI  - Electric Fields and Fast Protein Dynamics in Enzymes.
AB  - In recent years, there has been much discussion regarding the origin of enzymatic
      catalysis and whether including protein dynamics is necessary for understanding
      catalytic enhancement. An important contribution in this debate was made with the
      application of the vibrational Stark effect spectroscopy to measure electric
      fields in the active site. This provided a window on electric fields at the
      transition state in enzymatic reactions. We performed computational studies on
      two enzymes where we have shown that fast dynamics is part of the reaction
      mechanism and calculated the electric field near the bond-breaking event. We
      found that the fast motions that we had identified lead to an increase of the
      electric field, thus preparing an enzymatic configuration that is
      electrostatically favorable for the catalytic chemical step. We also studied the
      enzyme that has been the subject of Stark spectroscopy, ketosteroid isomerase,
      and found electric fields of a similar magnitude to the two previous examples.

PMID- 29220192
TI  - Fluidic Microactuation of Flexible Electrodes for Neural Recording.
AB  - Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire
      scaffolds have expanded the family of ultraflexible microelectrodes that can bend
      and flex with the natural movement of the brain, reduce the inflammatory
      response, and improve the stability of long-term neural recordings. However,
      current methods to implant these highly flexible electrodes rely on temporary
      stiffening agents that temporarily increase the electrode size and stiffness thus
      aggravating neural damage during implantation, which can lead to cell loss and
      glial activation that persists even after the stiffening agents are removed or
      dissolve. A method to deliver thin, ultraflexible electrodes deep into neural
      tissue without increasing the stiffness or size of the electrodes will enable
      minimally invasive electrical recordings from within the brain. Here we show that
      specially designed microfluidic devices can apply a tension force to
      ultraflexible electrodes that prevents buckling without increasing the thickness
      or stiffness of the electrode during implantation. Additionally, these "fluidic
      microdrives" allow us to precisely actuate the electrode position with micron
      scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used
      them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes for
      electrophysiology. We used this approach in three proof-of-concept experiments.
      First, we recorded compound action potentials in a soft model organism, the small
      cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic
      reticular nucleus in brain slices and recorded spontaneous and optogenetically
      evoked extracellular action potentials. Finally, we inserted electrodes more than
      4 mm deep into the brain of rats and detected spontaneous individual unit
      activity in both cortical and subcortical regions. Compared to syringe injection,
      fluidic microdrives do not penetrate the brain and prevent changes in
      intracranial pressure by diverting fluid away from the implantation site during
      insertion and actuation. Overall, the fluidic microdrive technology provides a
      robust new method to implant and actuate ultraflexible neural electrodes.

PMID- 29220193
TI  - Reactivity of Sulfur Molecules on MoO3 (010) Surface.
AB  - Two-dimensional and layered MoS2 is a promising candidate for next-generation
      electric devices due to its unique electronic, optical, and chemical properties.
      Chemical vapor deposition (CVD) is the most effective way to synthesize MoS2
      monolayer on a target substrate. During CVD synthesis, sulfidation of MoO3
      surface is a critical reaction step, which converts MoO3 to MoS2. However,
      initial reaction steps for the sulfidation of MoO3 remain to be fully understood.
      Here, we report first-principles quantum molecular dynamics (QMD) simulations for
      the initiation dynamics of sulfidation of MoO3 (010) surface using S2 and S8
      molecules. We found that S2 molecule is much more reactive on the MoO3 surface
      than S8 molecule. Furthermore, our QMD simulations revealed that a surface O
      vacancy on the MoO3 surface makes the sulfidation process preferable kinetically
      and thermodynamically. Our work clarifies an essential role of surface defects to
      initiate and accelerate the reaction of MoO3 and gas-phase sulfur precursors for
      CVD synthesis of MoS2 layers.

PMID- 29220194
TI  - Unraveling the Electronic Structure of Narrow Atomically Precise Chiral Graphene
      Nanoribbons.
AB  - Recent advances in graphene-nanoribbon-based research have demonstrated the
      controlled synthesis of chiral graphene nanoribbons (chGNRs) with atomic
      precision using strategies of on-surface chemistry. However, their electronic
      characterization, including typical figures of merit like band gap or frontier
      band's effective mass, has not yet been reported. We provide a detailed
      characterization of (3,1)-chGNRs on Au(111). The structure and epitaxy, as well
      as the electronic band structure of the ribbons, are analyzed by means of
      scanning tunneling microscopy and spectroscopy, angle-resolved photoemission, and
      density functional theory.

PMID- 29220195
TI  - Vibronic Ground-State Degeneracies and the Berry Phase: A Continuous Symmetry
      Perspective.
AB  - We develop a geometric construction to prove the inevitability of the electronic
      ground-state (adiabatic) Berry phase for a class of Jahn-Teller (JT) models with
      maximal continuous symmetries and N > 2 intersecting electronic states. Given
      that vibronic ground-state degeneracy in JT models may be seen as a consequence
      of the electronic Berry phase and that any JT problem may be obtained from the
      subset that we investigate in this Letter by symmetry-breaking, our arguments
      reveal the fundamental origin of the vibronic ground-state degeneracy of JT
      models.

PMID- 29220196
TI  - Compatibility of PEGylated Polymer Nanoparticles with the Biophysical Function of
      Lung Surfactant.
AB  - To minimize an unwanted interference of colloidal drug delivery vehicles with the
      biophysical functionality of lung surfactant, the surface of polymer
      nanoparticles was modified with poly(ethylene glycol) (PEGylation). Plain
      poly(lactide) nanoparticles provoked a statistically relevant decrease in the
      surface activity of the naturally derived lung surfactant, Alveofact. By
      contrast, the extent of lung surfactant inhibition induced by PEGylated polymer
      nanoparticles was significantly attenuated. Here, escalations of the PEG coating
      layer thickness (>3 nm, with a chain-to-chain distance of <=4 nm) on the
      colloidal surface were capable of circumventing bioadverse effects. Accordingly,
      polymer nanoparticles equipped with PEG chains with a molecular weight above 2-5
      kDa were compatible with the biophysical function of Alveofact. Overall,
      PEGylation of polymer nanoparticles presents a promising approach for the
      development of inhalation nanomedicines revealing negligible effects on the
      surface activity of the lining layer present in the deep lungs.

PMID- 29220197
TI  - Lewis Base-Boryl Radicals Enabled the Desulfurizative Reduction and Annulation of
      Thioamides.
AB  - A new protocol for radical transformations of thioamides promoted by Lewis base
      boryl radicals is reported. The desulfurizative reduction to access organic
      amines was enabled utilizing 4-dimethylaminopyridine-BH3 as the boryl radical
      precursor and PhSH as the polarity reversal catalyst. Alternatively, the chain
      process for unsaturated thioamides was switched to an annulation reaction using N
      heterocyclic carbene-BH3 as the boryl radical precursor and sterically bulky
      Ph3CSH as the catalyst, allowing for the construction of N-heterocyclic and
      carbocyclic skeletons.

PMID- 29220198
TI  - Biobanking Genetic Material for Agricultural Animal Species.
AB  - Biobanking animal germplasm and tissues is a major component of conserving
      genetic resources. Effectively constructing such gene banks requires an
      understanding and evaluation of genetic resources, the ability to conserve
      various tissues through cryopreservation, and a robust information technology
      infrastructure to allow managers and potential users to fully understand and make
      use of the collection. Progress has been made internationally in developing
      national genetic resource collections. As these collections have been developed,
      it has become apparent that gene banks can serve a multitude of roles, thereby
      serving short- and long-term needs of research communities and industry. This
      article documents the development of gene banks and provides examples of how they
      have been used to date and the extent to which they have captured genetic
      diversity for future use.

PMID- 29220199
TI  - Risk Factors for Gaps in Care during Transfer from Pediatric to Adult Cystic
      Fibrosis Programs in the United States.
AB  - RATIONALE: With improved survival into adulthood, the number of dedicated adult
      cystic fibrosis (CF) care programs has expanded in the United States over the
      past decade. Transfer from pediatric to adult CF programs represents a potential
      time for lapses in recommended health care. OBJECTIVES: To describe variability
      in transfer between pediatric and adult CF care programs and to identify factors
      associated with prolonged gaps in care. METHODS: Using the U.S. CF Foundation
      Patient Registry, we identified individuals with CF who transferred care from a
      pediatric to an adult CF care program during 2007 to 2013. A gap in care was
      defined as the time in days between the last recorded pediatric encounter and the
      first recorded adult encounter. A hierarchical multivariable regression model was
      applied to investigate the effect of program- and patient-level factors on gaps
      in care. RESULTS: There were 1,946 individuals at 155 pediatric CF programs who
      transferred to an adult CF program during the analytic period. The mean age at
      transfer was 21.1 years, with 68% transferring care between ages 18 and 21 years.
      The mean gap in care during transfer was 183 days (median, 106 d; range, 2-1,843
      d); 47% had a less than 100-day gap, and 13% had a greater than or equal to 365
      day gap (prolonged gap). Prolonged gaps in care were more likely to occur among
      those younger than age 18 years (odds ratio, 3.33; 95% confidence interval, 2.06
      5.37) at the time of transfer and those who transferred to an adult program that
      was in a different city from their pediatric or affiliate program (odds ratio,
      2.16; 95% confidence interval, 1.48-3.17). Having any health insurance coverage
      was associated with decreased likelihood of prolonged gaps (private insurance vs.
      no insurance [odds ratio, 0.15; 95% confidence interval, 0.09-0.23] or any
      government insurance versus no insurance [odds ratio, 0.11; 95% confidence
      interval, 0.07-0.18]). Lung function, nutritional status, and receipt of
      intravenous antibiotics in the final year of pediatric care were not associated
      with the length of gap in care during transfer. CONCLUSIONS: In the United
      States, the majority of individuals transferring from pediatric to adult CF care
      do so between ages 18 and 21 years. A minority had a gap greater than or equal to
      365 days during transfer to adult care, suggesting that most did not have a
      disruption in recommended quarterly care visits during the transfer period. Risk
      factors for prolonged gaps in care include younger age at transfer, lack of
      health insurance, and relocation. Care coordination during transition in CF may
      minimize lapses in care by identifying and more closely addressing the needs of
      individuals at highest risk.

PMID- 29220201
TI  - Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche.
AB  - Stem cells are a powerful resource for many applications including regenerative
      medicine, patient-specific disease modeling, and toxicology screening. However,
      eliciting the desired behavior from stem cells, such as expansion in a naive
      state or differentiation into a particular mature lineage, remains challenging.
      Drawing inspiration from the native stem cell niche, hydrogel platforms have been
      developed to regulate stem cell fate by controlling microenvironmental parameters
      including matrix mechanics, degradability, cell-adhesive ligand presentation,
      local microstructure, and cell-cell interactions. We survey techniques for
      modulating hydrogel properties and review the effects of microenvironmental
      parameters on maintaining stemness and controlling differentiation for a variety
      of stem cell types. Looking forward, we envision future hydrogel designs spanning
      a spectrum of complexity, ranging from simple, fully defined materials for
      industrial expansion of stem cells to complex, biomimetic systems for organotypic
      cell culture models.

PMID- 29220200
TI  - A Practical Approach to Severe Asthma in Children.
AB  - Severe asthma accounts for only a small proportion of the children with asthma
      but a disproportionately high amount of resource utilization and morbidity. It is
      a heterogeneous entity and requires a step-wise, evidence-based approach to
      evaluation and management by pediatric subspecialists. The first step is to
      confirm the diagnosis by eliciting confirmatory history and objective evidence of
      asthma and excluding possible masquerading diagnoses. The next step is to
      differentiate difficult-to-treat asthma, asthma that can be controlled with
      appropriate management, from asthma that requires the highest level of therapy to
      maintain control or remains uncontrolled despite management optimization.
      Evaluation of difficult-to-treat asthma includes an assessment of medication
      delivery, the home environment, and, if possible, the school and other frequented
      locations, the psychosocial situation, and comorbid conditions. Once identified,
      aggressive management of issues related to poor adherence and drug delivery,
      remediation of environmental triggers, and treatment of comorbid conditions is
      necessary to characterize the degree of control that can be achieved with
      standard therapies. For the small proportion of patients whose disease remains
      poorly controlled with these interventions, the clinician may assess steroid
      responsiveness and determine the inflammatory pattern and eligibility for
      biologic therapies. Management of severe asthma refractory to traditional
      therapies involves considering the various biologic and other newly approved
      treatments as well as emerging therapies based on the individual patient
      characteristics.

PMID- 29220202
TI  - Comparison of UV-C and Pulsed UV Light Treatments for Reduction of Salmonella,
      Listeria monocytogenes, and Enterohemorrhagic Escherichia coli on Eggs.
AB  - Ten percent of all strong-evidence foodborne outbreaks in the European Union are
      caused by Salmonella related to eggs and egg products. UV light may be used to
      decontaminate egg surfaces and reduce the risk of human salmonellosis infections.
      The efficiency of continuous UV-C (254 nm) and pulsed UV light for reducing the
      viability of Salmonella Enteritidis, Listeria monocytogenes, and
      enterohemorrhagic Escherichia coli on eggs was thoroughly compared. Bacterial
      cells were exposed to UV-C light at fluences from 0.05 to 3.0 J/cm2 (10 mW/cm2,
      for 5 to 300 s) and pulsed UV light at fluences from 1.25 to 18.0 J/cm2,
      resulting in reductions ranging from 1.6 to 3.8 log, depending on conditions
      used. Using UV-C light, it was possible to achieve higher reductions at lower
      fluences compared with pulsed UV light. When Salmonella was stacked on a small
      area or shielded in feces, the pulsed UV light seemed to have a higher
      penetration capacity and gave higher bacterial reductions. Microscopy imaging and
      attempts to contaminate the interior of the eggs with Salmonella through the
      eggshell demonstrated that the integrity of the eggshell was maintained after UV
      light treatments. Only minor sensory changes were reported by panelists when the
      highest UV doses were used. UV-C and pulsed UV light treatments appear to be
      useful decontamination technologies that can be implemented in continuous
      processing.

PMID- 29220203
TI  - Recent advances in fertility preservation and counseling for female cancer
      patients.
AB  - INTRODUCTION: Ensuring quality of life for increasing numbers of women surviving
      cancer has become a key challenge. Patients need to be counseled on potential
      fertility loss resulting from gonadotoxic treatments, and referred to fertility
      specialists to discuss existing options and available results. Areas covered:
      Fertility preservation options have existed for over twenty years. The proposed
      fertility preservation approach depends on patient age, the urgency of required
      chemotherapy, and psychosocial factors such as financial concerns, especially in
      countries where techniques are not covered by social security. Efficacy in terms
      of pregnancy rates has been demonstrated with frozen-thawed embryos, oocytes and
      re-implanted ovarian tissue. Appropriate counseling by oncologists is on the
      increase, despite persistently low rates of referral to fertility specialists.
      Expert commentary: Access to oncofertility services is steadily improving,
      facilitated by the growing involvement of public healthcare systems and sustained
      efforts all over the world to establish specific oncofertility programs. Early
      referral to reproductive specialists before initiation of chemo/radiotherapy is
      crucial to success in the field of female fertility preservation. In the near
      future, efforts should focus on increasing patient referrals and establishing
      international registries on short- and long-term outcomes of fertility
      preservation strategies.

PMID- 29220204
TI  - Attention Deficit Hyperactivity Disorder (ADHD): Controversy, Developmental
      Mechanisms, and Multiple Levels of Analysis.
AB  - Controversy abounds regarding the symptom dimensions of attention problems,
      impulsivity, and hyperactivity, developmentally extreme and impairing levels of
      which compose the diagnostic category of attention deficit hyperactivity disorder
      (ADHD). I highlight causal factors, underlying mechanisms, developmental
      trajectories, and female manifestations of ADHD, integrating the psychobiological
      underpinnings of this syndrome with contextual factors related to its clinical
      presentation, impairments, and soaring increases in diagnosed prevalence. Indeed,
      despite strong heritability, ADHD is expressed via transactional patterns of
      influence linked to family-, school-, peer-, neighborhood-, and policy-related
      factors. Moreover, intervention strategies must take into account both
      pharmacologic and behavioral modalities if the goal is to enhance competencies,
      rather than symptom reduction per se. A comprehensive understanding of ADHD
      mandates multiple levels of analysis-spanning genes, neurotransmission, brain
      pathways, individual skill levels, family socialization, peer relationships, and
      educational and cultural forces-which must be integrated and synthesized to
      surpass reductionist accounts, reduce stigma, and maximize the impact of
      prevention- and intervention-related efforts.

PMID- 29220206
TI  - Aerobic training but no resistance training increases SIRT3 in skeletal muscle of
      sedentary obese male adolescents.
AB  - In recent years, prevalence of obesity in children and adolescents has increased.
      A strategy for prevention and management of obesity is aerobic training (AT) due
      to its effectiveness to decrease fat mass. AT increases the content of SIRT3, a
      mitochondrial protein that increases the expression of PGC-1alpha and NFR1,
      thereby enhances mitochondrial function and metabolic health. Resistance training
      (RT) provides metabolic benefits but its effect on SIRT3 content is unknown. To
      compare the effect of AT and RT on SIRT3, PGC-1alpha and NRF-1 protein levels in
      skeletal muscle of sedentary obese adolescents. Twenty-seven sedentary obese male
      adolescents (age: 16.7 +/- 0.9 years; BMI: 33.7 +/- 4.3 kg/m2) completed a 1
      month control period prior to randomization to one of two supervised exercise
      protocols: AT (3 days/week, 40 min/day, 70-80% peak heart rate) or RT (3
      days/week, 11 exercises, 2 sets/exercise, 12 repetitions/set) for 12 weeks.
      Biopsies were obtained from the vastus lateralis muscle before and after 12 weeks
      to analyse SIRT3, PGC-1alpha and NRF-1 proteins content. Peak oxygen consumption
      (VO2peak) and anthropometric variables were evaluated before and after training.
      AT increased SIRT3 content, which was associated with improvements in PGC-1alpha
      content and body fat percentage. RT did not affect SIRT3 or PGC-1alpha. VO2peak
      increased only in AT. The increase in muscle mitochondrial SIRT3 was observed
      only following AT. In contrast, RT increased muscle mass without improving SIRT3
      in obese male adolescents.

PMID- 29220205
TI  - Hematocrit Is Associated with Thermal Tolerance and Modulated by Developmental
      Temperature in Juvenile Chinook Salmon.
AB  - To evaluate whether oxygen-carrying capacity influences thermal tolerance in
      fishes, we reared four Chinook salmon families in present-day (+0 degrees C) and
      possible future (+4 degrees C) temperatures and assessed the response of
      hematocrit (Hct) to acute temperature stress. In the +4 degrees C treatment, Hct
      increased above control levels when juvenile fish were exposed to their critical
      thermal maximum (CTmax). Conversely, no effect of temperature stress on Hct was
      found in the +0 degrees C treatment. Hct was positively associated with CTmax
      ([Formula: see text]; [Formula: see text]), contributing to the CTmax of the +4
      degrees C treatment being significantly higher than that of the +0 degrees C
      treatment (mean +/- SD, [Formula: see text] and [Formula: see text],
      respectively). The association between CTmax and Hct found here supports the
      hypothesis that thermal tolerance is affected by oxygen supply to tissue.
      Moreover, the developmental plasticity of CTmax and Hct could represent an
      adaptive mechanism for salmon faced with climate change.

PMID- 29220207
TI  - MR Imaging of Muscle Trauma: Anatomy, Biomechanics, Pathophysiology, and Imaging
      Appearance.
AB  - Muscle is an important component of the muscle-tendon-bone unit, driving skeletal
      motion through contractions that alter the length of the muscle. The muscle and
      myotendinous junction (MTJ) are most commonly injured in the young adult, as a
      result of indirect mechanisms such as overuse or stretching, direct impact
      (penetrating or nonpenetrating), or dysfunction of the supporting connective
      tissues. Magnetic resonance (MR) imaging is widely used for assessment of muscle
      injuries. This review illustrates the MR imaging appearance of a broad spectrum
      of acute, subacute, and chronic traumatic lesions of muscle, highlighting the
      pathophysiology, biomechanics, and anatomic considerations underlying these
      lesions. Concentric (shortening) contractions are more powerful, but it is
      eccentric (lengthening) contractions that produce the greatest muscle tension,
      leading to indirect injuries such as delayed-onset muscle soreness (DOMS) and
      muscle strain. Strain is the most commonly encountered muscle injury and is
      characteristically located at the MTJ, where maximal stress accumulates during
      eccentric exercise. The risk of strain varies among muscles based on their fiber
      composition, size, length, and architecture, with pennate muscles being at
      highest risk. Direct impact to muscle results in laceration or contusion, often
      accompanied by intramuscular interstitial hemorrhage and hematoma. Disorders
      related to the muscle's collagen framework include compartment syndrome, which is
      related to acute or episodic increases in pressure, and muscle herniation through
      anatomic defects in the overlying fascia. The healing response after muscle
      trauma can result in regeneration, degeneration with fibrosis and fatty
      replacement, or disordered tissue proliferation as seen in myositis ossificans.
      In athletes, accurate grading of the severity and precise location of injury is
      necessary to guide rehabilitation planning to prevent reinjury and ensure
      adequate healing. In elite athletes, MR imaging grading of muscle trauma plays an
      increasingly important role in recently developed comprehensive grading systems
      that are replacing the imprecise three-grade injury classification system
      currently used. (c)RSNA, 2017.

PMID- 29220208
TI  - Changing Utilization of Noninvasive Diagnostic Imaging Over 2 Decades: An
      Examination Family-Focused Analysis of Medicare Claims Using the Neiman Imaging
      Types of Service Categorization System.
AB  - OBJECTIVE: The objective of our study was to use a new modality and body region
      categorization system to assess changing utilization of noninvasive diagnostic
      imaging in the Medicare fee-for-service population over a recent 20-year period
      (1994-2013). MATERIALS AND METHODS: All Medicare Part B Physician Fee Schedule
      services billed between 1994 and 2013 were identified using Physician/Supplier
      Procedure Summary master files. Billed codes for diagnostic imaging were
      classified using the Neiman Imaging Types of Service (NITOS) coding system by
      both modality and body region. Utilization rates per 1000 beneficiaries were
      calculated for families of services. RESULTS: Among all diagnostic imaging
      modalities, growth was greatest for MRI (+312%) and CT (+151%) and was lower for
      ultrasound, nuclear medicine, and radiography and fluoroscopy (range, +1% to
      +31%). Among body regions, service growth was greatest for brain (+126%) and
      spine (+74%) imaging; showed milder growth (range, +18% to +67%) for imaging of
      the head and neck, breast, abdomen and pelvis, and extremity; and showed slight
      declines (range, -2% to -7%) for cardiac and chest imaging overall. The following
      specific imaging service families showed massive (> +100%) growth: cardiac CT,
      cardiac MRI, and breast MRI. CONCLUSION: NITOS categorization permits
      identification of temporal shifts in noninvasive diagnostic imaging by specific
      modality- and region-focused families, providing a granular understanding and
      reproducible analysis of global changes in imaging overall. Service family-level
      perspectives may help inform ongoing policy efforts to optimize imaging
      utilization and appropriateness.

PMID- 29220209
TI  - Making Time for Patients: Positive Impact of Direct Patient Reporting.
AB  - OBJECTIVE: Using a novel patient-centric approach, we assessed the impact of
      direct patient radiology reporting on the patient experience and patient
      perception of radiologists in a high-volume head and neck clinic. MATERIALS AND
      METHODS: A single head and neck surgeon at a large academic center identified
      prospective outpatients who met the following inclusion criteria: having received
      treatment for head and neck cancer and having recently undergone surveillance
      imaging using the Neck Imaging Reporting and Data System template at our
      institution. The surgeon introduced the concept and gave patients a survey with
      questions before and after the radiology consultation. The radiologist met with
      the patient in the head and neck clinic's examination room, explaining the role
      of the radiologist and reviewing imaging findings. RESULTS: Twenty-seven patients
      completed surveys. An improved understanding of the role of the radiologist was
      noted (41% of patients before consultation vs 67% after consultation). After the
      consultation, fewer patients (56-22%) wanted to hear from the referring physician
      only, and more patients wanted to hear from the radiologist only (26-44%) or from
      both the referring physician and the radiologist (19-33%). A total of 70-93% of
      patients had an improved understanding of imaging findings and follow-up
      recommendations after meeting with the radiologist. Most patients expressed an
      interest in reviewing future studies with a radiologist (93%) and found the
      consultation helpful (96%). CONCLUSION: Direct patient reporting by the
      radiologist is feasible in a high-volume head and neck clinic and has a positive
      impact on the patient experience. Major factors that enabled direct patient
      reporting included our embedded reading room and the use of a standardized
      reporting template. After the consultation, more patients wanted to receive
      information from the radiologist and had a better understanding of the imaging
      results.

PMID- 29220210
TI  - Contrast-Enhanced Ultrasound of the Liver: Optimizing Technique and Clinical
      Applications.
AB  - OBJECTIVE: The purpose of this article is to review the general principles,
      technique, and clinical applications of contrast-enhanced ultrasound of the
      liver. CONCLUSION: Proper technique and optimization of contrast-enhanced
      ultrasound require a balance between maintaining the integrity of the microbubble
      contrast agent and preserving the ultrasound signal. Established and emerging
      applications in the liver include diagnosis of focal lesions, aiding ultrasound
      guided intervention, monitoring of therapy, and aiding surgical management.

PMID- 29220211
TI  - Percutaneous Image-Guided Cryoneurolysis.
AB  - OBJECTIVE: The aim of this article is to review the available evidence regarding
      image-guided percutaneous cryoneurolysis, with a focus on indications, technique,
      efficacy, and potential complications. CONCLUSION: Percutaneous image-guided
      cryoneurolysis is safe and effective for the management of several well-described
      syndromes involving neuropathic pain. Additional rigorous prospective study is
      warranted to further define the efficacy and specific role of these
      interventions.

PMID- 29220212
TI  - Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT
      for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.
AB  - OBJECTIVE: The objective of this study was to compare the capability of xenon
      enhanced area-detector CT (ADCT) performed with a subtraction technique and
      coregistered 81mKr-ventilation SPECT/CT for the assessment of pulmonary
      functional loss and disease severity in smokers. SUBJECTS AND METHODS: Forty-six
      consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent
      prospective unenhanced and xenon-enhanced ADCT, 81mKr-ventilation SPECT/CT, and
      pulmonary function tests. Disease severity was evaluated according to the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based
      functional lung volume (FLV), the percentage of wall area to total airway area
      (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for
      each smoker. All indexes were correlated with percentage of forced expiratory
      volume in 1 second (%FEV1) using step-wise regression analyses, and univariate
      and multivariate logistic regression analyses were performed. In addition, the
      diagnostic accuracy of the proposed model was compared with that of each
      radiologic index by means of McNemar analysis. RESULTS: Multivariate logistic
      regression showed that %FEV1 was significantly affected (r = 0.77, r2 = 0.59) by
      two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p <
      0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression
      analyses indicated that all indexes significantly affected GOLD classification (p
      < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV
      on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD
      classification (p < 0.0001). The diagnostic accuracy of the proposed model was
      significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA%
      (p = 0.008). CONCLUSION: Xenon-enhanced ADCT is more effective than 81mKr
      ventilation SPECT/CT for the assessment of pulmonary functional loss and disease
      severity.

PMID- 29220214
TI  - Particle Capture by the Gills of Dreissena polymorpha: Structure and Function of
      Latero-frontal Cirri.
AB  - Microscopic techniques were used to examine the role of gill cirri in particle
      capture by Dreissena polymorpha. The latero-frontal cirri, formed from two fused
      ciliary plates, consist of about 40 pairs of cilia. Each cilium in the plate
      contains a typical 9 + 2 axoneme in the fused region of the cirrus, but the
      structure of the axoneme in the long, free ciliary tips is reduced. The cilia in
      a cirrus are graded in length, with the shortest cilia positioned frontally. The
      cirral cilia move in unison, allowing the cirrus to move from a flexed position
      with its tip arched over the front of the gill filament, to an extended position
      with the cirrus projected in the plane of the latero-frontal cell and extending
      across the interfilament space. In the latter position, the free ciliary tips of
      opposing and neighboring cirri form a "trap" (net) with a spacing of about 0.5
      MUm. Observations with laser confocal microscopy indicated that these structures
      can physically trap particles <1 MUm in diameter. Particles captured by the
      extended cirri are moved to the frontal surface of the gill, where the cirri are
      swept by the lateralmost frontal cilia. During cirral movement the shift from
      extended to flexed position is, in part, achieved by the base of the cirrus
      pivoting at a hinge region. Morphologically, the hinge region shows axonemal
      specializations that consist of electron-dense plates and other structures of
      undefined function that may be important in the overall movement of the cirrus.
      In addition to trapping by cirri, we also observed particles moving in the water
      currents, particularly in the frontal current located over the apical surface of
      the filament, suggesting that some particles are captured in these water currents
      without being physically trapped. Probably, therefore, trapping by the cirri and
      establishment of water currents by the filaments both participate in the
      interception of particles by Dreissena polymorpha.

PMID- 29220213
TI  - Clinical Application of Biparametric MRI Texture Analysis for Detection and
      Evaluation of High-Grade Prostate Cancer in Zone-Specific Regions.
AB  - OBJECTIVE: The purpose of this study was to investigate the performance of
      biparametric MRI texture analysis (TA) in detecting and evaluating high-grade
      prostate cancer in zone-specific regions. MATERIALS AND METHODS: A retrospective
      study included 184 consecutively registered biopsy-naive patients in whom
      prostate cancer was suspected who were undergoing multiparametric prostate MRI.
      MR images were scored and evaluated by two readers using the Prostate Imaging
      Reporting and Data System version 2 (PI-RADSv2) and biparametric MRI TA in
      separate sessions. Interobserver agreement on PI-RADSv2 score and textural
      parameters of biparametric MRI was evaluated. The logistic regression model based
      on TA was built for different zones of the prostate. ROC analysis was used to
      compare the TA-based model with other parameters alone. The correlation of each
      parameter with Gleason score of high-grade prostate cancer was also assessed.
      RESULTS: Reader reliability ranged from moderate to good for PI-RADSv2 (Cohen
      kappa = 0.525-0.616) and from good to excellent for textural metrics (intraclass
      correlation coefficient, 0.745-0.925). Diagnostic performance was significantly
      improved by use of the TA-based model (transition zone AUC, 0.87; peripheral zone
      AUC, 0.89) in comparison with PI-RADSv2 and other texture parameters alone. For
      the transition zone, entropy had moderate to good correlation with the Gleason
      score of high-grade prostate cancer (r = 0.562, p = 0.004). In the peripheral
      zone, entropy (r = 0.614, p = 0.003) and inertia (r = 0.663, p = 0.002) had
      moderate to good correlations with Gleason score. CONCLUSION: The results of this
      clinical study indicate that a TA-based model that includes biparametric MRI can
      be used for identifying high-grade prostate cancer and that specific parameters
      extracted from TA may be additional tools for assessing tumor aggressiveness.

PMID- 29220215
TI  - Subunit Composition of the Crustacean Hemocyanins: Divergence in Incipient
      Speciation.
AB  - The monomeric subunit composition of the oxygen carrier hemocyanin was examined
      in samples of the Sesarma reticulatum complex and of Uca minax, both of which are
      believed to be in the process of speciation. The samples were taken on the
      Atlantic and Gulf of Mexico coasts, from disjunct populations that are believed
      to have been isolated by the Florida peninsula since the retreat of the last
      glacier. In Atlantic and Gulf samples of the S. reticulatum complex, which is
      believed to be in the terminal stages of speciation, the hemocyanins differed
      qualitatively. Several electrophoretic bands found in one group, including an
      invariant band, were totally absent from the other. This difference exceeds that
      reported in a previous investigation of a variety of polymorphic allozymes in
      this species complex. It also exceeds the physiologically labile differences in
      hemocyanins found previously within a panmictic species of brachyuran
      crustaceans. In U. minax, which is believed to have diverged less, Atlantic and
      Gulf animals expressed the same number of electrophoretic bands at exactly the
      same positions. Nonetheless, highly significant differences in band frequencies
      distinguished both Atlantic samples from the Gulf sample, and somewhat less
      significant differences distinguished the Atlantic cold temperate zone samples
      from the warm temperate zone ones. The phenotypes of the major bands, defined as
      those present in high densities, qualitatively distinguished Atlantic from Gulf
      animals, but they did not differentiate the two Atlantic samples. The difference
      between Atlantic and Gulf members of this species also exceeds that found
      previously among polymorphic allozymes. These findings further support the
      hypothesis that the hemocyanins are among the first proteins to diverge
      structurally in brachyuran speciation.

PMID- 29220216
TI  - Serotonergic Ligands Induce Spawning but not Oocyte Maturation in the Bivalve
      Mactra chinensis from Central Japan.
AB  - We examined the spawning sensitivity to serotonin and serotonergic ligands in the
      Japanese bivalve Mactra chinensis. Spawning was induced by both injected and
      externally applied scrotonin (5-hydroxytryptamine. 5-HT). The vertebrate 5-HT2
      receptor agonist alpha-methyl 5-HT and the selective 5HT1A agonist 8-OH-DPAT were
      also effective at inducing spawning. However TFMPP (m
      trifluoromethylphenylpiperazine, a verterbrate 5-HT1 receptor agonist) and 1
      methyl-chlorophenyl biguanide (a vertebrate 5-HT3 agonist) were not effective
      spawning inducers. The 5-HT-induced spawning was blocked by mianserin (a
      vertebrate 5-HT2 antagonist). The rank order of potency of the agonists was: 5-HT
      > alpha-methyl 5-HT > 8-OH-DPAT > TFMPP > 1-methyl-chlorophenyl biguanide; these
      data support a growing body of literature invoking a mixed 5-HT1/5-HT2
      pharmacological profile for serotonin receptors mediating reproductive processes
      in bivalves. However, neither 5-HT nor 8-OH-DPAT induced germinal vesicle
      breakdown (GVBD) in Mactra oocytes. Sperm induced GVBD in a high percentage of
      oocytes. This is the first report of a bivalve in which spawning, but not GVBD,
      can be induced by 5-HT. This result might be expected because Mactra spawns
      germinal vesicle oocytes that normally undergo GVBD upon fertilization, but is in
      contrast to the case of the closely related Spisula spp. in which serotonin
      induces both processes. The ability of 5-HT to induce spawning but not GVBD makes
      Mactra chinensis a model organism for studying spawning and meiotic mechanisms in
      bivalves.

PMID- 29220217
TI  - Neuroethology of Orientation and Navigation: Introduction.

PMID- 29220218
TI  - Information Is Where You Find It.
AB  - A basic problem of foraging is how to obtain information about the location and
      quality of food. Relevant information is obtained from immediate stimulation,
      from previous sensory experience stored in memory, and through the genes.
      Apparently, even the simplest organisms can use information from all these
      sources. A good example comes from infective juveniles of the plant-parasitic
      nematode Meloidogyne incognita, which only feed after they locate the root of a
      suitable host plant. Available evidence indicates that carbon dioxide from host
      roots attracts the juveniles but that it would also be useful for the juveniles
      to move to an optimal soil depth in which to search for chemical gradients.
      Although there are few cues to soil depth, M. incognita is able to solve this
      problem in a surprising way. Juveniles can orient to extremely shallow
      temperature gradients that are nearly always present in the environment. The
      juveniles also have the peculiar property of moving toward a preferred
      temperature that is set several degrees above the temperature to which they are
      acclimated. Computer modeling of this behavior demonstrates that it provides a
      mechanism for moving to a particular soil depth. Although average temperature is
      the same at all depths, the amplitude of daily temperature variation declines
      with depth and provides the required information, which is extracted by
      interactions among environmental temperature, preferred temperature, rate of
      acclimation, rate of locomotion, and temperature range of locomotion.
      Pseudoplasmodia of the slime mold Dictyostelium have similar capabilities. This
      behavior resembles true navigation in that the stimulus used for guidance has no
      connection to the goal and suggests that even simple organisms can extract useful
      information from surprisingly complex stimulus patterns.

PMID- 29220219
TI  - Sensory Ecology: Introduction.

PMID- 29220220
TI  - Finding Food: Neuroethological Aspects of Foraging. Introduction to the
      Proceedings of a Symposium in Honor of Vincent Gaston Dethier (1915-1993).

PMID- 29220221
TI  - Dynamic Encoding of Odors With Oscillating Neuronal Assemblies in the Locust
      Brain.
AB  - The computational rules followed by the brain to encode complex, multidimensional
      stimuli such as natural odors are not well understood. In this review, we
      summarize results obtained in the olfactory system of an insect and present a
      hypothesis for odor representation in the brain. We propose that individual odors
      are represented by ensembles of neurons that are distributed both in space (the
      specific identities of the neurons forming an ensemble) and in time (the time at
      which each neuron participates in the ensemble response). In addition, we discuss
      the potential roles that periodic synchronization (oscillations) might play in
      this complex process.

PMID- 29220223
TI  - Temporal Shifts in Foraging Strategy: Introduction.

PMID- 29220222
TI  - Eddy Chemotaxis and Odor Landscapes: Exploration of Nature With Animal Sensors.

PMID- 29220224
TI  - Evolution of Intragonadal Development in the Diminutive Asterinid Sea Stars
      Patiriella vivipara and P. parvivipara with an Overview of Development in the
      Asterinidae.
AB  - The diminutive asterinid sea stars Patiriella vivipara and P. parvivipara
      incubate their embryos in the gonads to the advanced juvenile stage. Despite the
      small size of their eggs (135-150 MUm diameter), development is lecithotrophic.
      Development proceeds through the wrinkled blastula, gastrula, and brachiolaria
      larval stages. The gastrulae and larvae are uniformly ciliated and swim,
      propelled by the cilia, in the gonadal fluid. The brachiolaria is pear-shaped and
      has a vestigial brachiolar attachment complex composed of three small brachia. At
      no stage in development are the embryos attached to the gonad. Metamorphosis
      occurs as the larvae swim in the gonadal lumen. Internal development involves
      formation of one large enterocoel at the anterior end of the archenteron and one
      small posterior enterocoel on the left side of the archenteron. The archenteron
      closes to form the rudiment for the adult gut. As a result of the small size of
      the egg and the nonfeeding mode of development, the larvae of P. vivipara and P.
      parvivipara are minute, about 270 MUm and 210 {mu}m in length, respectively.
      Newly metamorphosed juveniles are about 240 MUm and 310 MUm in diameter,
      respectively. Postmetamorphic development involves substantial growth of the
      juveniles, which leave the parent at a diameter between 1.0 and 5.0 mm. The
      presence of a vestigial brachiolar complex and lecithotrophic development
      indicates that these species had a free-living lecithotrophic brachiolaria in
      their ancestry. We suggest that the evolution of viviparity in Patiriella sp.
      involved retention of a large egg by an ancestor that had a lecithotrophic
      brachiolaria followed by a secondary reduction in the size of the ovum and
      simplification of the larva. The range of life histories seen in Patiriella is
      atypical of asteroid genera and supports the contention that the evolution of
      viviparity and other modes of modified development in the Asteroidea follows
      phylogenetic lineages.

PMID- 29220225
TI  - Localization of Myosin on Tubulovesicular Organelles in the Squid Giant Axon by
      Immuno-EM.

PMID- 29220227
TI  - Method for Visualizing Filaments in Axoplasm by Electron Microscopy.

PMID- 29220226
TI  - Mitotic Spindle Fine Structures Observed With Polarized Light.

PMID- 29220228
TI  - An Ancient Chemosensory Mechanism Brings New Life to Coral Reefs.
AB  - The first scleractinians, progenitors of modern corals, began to appear 240
      million years ago; by the late Jurassic (150 Ma) most families of modern corals
      had evolved and begun forming reefs (1, 2). Mechanisms controlling the
      recruitment of new corals to sustain these structures are, however, poorly
      understood (3). Corals, like many marine invertebrates, begin life as soft-bodied
      larvae that are dispersed in the plankton (3, 4). As the first step in developing
      a calcified coral colony, the larva must settle out of the plankton onto a
      suitable substratum and metamorphose to the single calcified polyp stage cemented
      to the reef (3, 5). Our analyses of the metamorphic requirements of larvae in
      divergent coral families surprised us by revealing the existence of a common
      chemosensory mechanism that is required to bring larvae out of the plankton and
      onto the reef. This mechanism appears to be quite old, predating both the
      phylogenetic divergence of these coral families and the development of different
      modes of coral reproduction.

PMID- 29220229
TI  - Birefringence Measurements of the Actin Bundle in the Acrosomal Processes of
      Limulus Sperm.

PMID- 29220230
TI  - Acute Cytotoxic Allogeneic Histoincompatibility Reactions Involving Gray Cells in
      the Marine Sponge, Callyspongia diffusa.
AB  - A variety of procedures were used in a study of the histoincompatibility
      reactions of Callyspongia diffusa. Rejection reactions as traditionally tested
      between laterally apposed intact fingers cut from two different sponges require
      about a week of contact to exhibit cytotoxicity. In a miniaturized assay
      involving reactions between small pieces of tissue snipped from sponges with
      scissors and pushed together on an insect pin, cytotoxicity is evident within 48
      hours of contact. Reactions of cells dissociated by divalent cation removal and
      allowed to reaggregate in seawater were also studied. Aggregates produced from
      allogeneic mixtures of cells from two individuals were killed by internal
      cytotoxic reactions within 36 hours of the initiation of aggregation. After only
      one hour of aggregation, aggregates from allogeneic mixtures were significantly
      smaller than aggregates of cells from a single individual. This rapid slowing of
      aggregation is the earliest response to allogeneic contact that we noted and does
      not appear to reflect early cytotoxic processes. Apposition of an aggregate
      containing cells from one sponge to an aggregate containing cells from a second
      individual leads to mutual destruction. Aggregates harvested and apposed 4 hours
      after initiation of aggregation begin to show mutual cytotoxicity at 36 hours of
      contact. Aggregates placed in contact 48 hours after the initiation of
      aggregation exhibit cytotoxicity within 8 hours. These rapidly reacting 48-hour
      aggregates exhibit a pronounced accumulation of gray cells at the boundary of
      allogeneic contact by 8 hours. These results are interpreted as indicating at
      least five steps in the histoincompatibility reactions of C. diffusa: (1)
      recognition soon after allogeneic contact; (2) generation of signals that
      suppress cell aggregation and cell movement and attract gray cells to the
      boundary of contact; (3) acceleration of the sponge immune response--including
      the responsiveness of gray cells to accumulate at the boundary of allogeneic
      contact--by tissue trauma produced when the tissue is cut or dissociated it into
      individual cells; (4) arrival of gray cells at the boundary of allogeneic
      contact; and (5) initiation of cytotoxic processes.

PMID- 29220231
TI  - Characterization of Methyl Transferase Activity in the Mandibular Organ of the
      American Lobster, Homarus americanus.

PMID- 29220232
TI  - Arteries of the Foreflipper of the Harbor Seal (Phoca vitulina) as Represented by
      Contrast Arteriography.

PMID- 29220233
TI  - Direct Observation of Contact Digestion in Inside-Out Oriented Aurelia aurita
      Polyps.

PMID- 29220234
TI  - Digital Unsharp Masking Reveals Fine Detail in Images Obtained with New Spinning
      disk Confocal Microscope.

PMID- 29220236
TI  - Effect of SR Calcium Pump Inhibition on Relaxation and Power from Scup Red
      Muscle.

PMID- 29220235
TI  - Primordial Germ Cells of Synaptula hydriformis (Holothuroidea; Echinodermata) Are
      Epithelial Flagellated-Collar Cells: Their Apical-Basal Polarity Becomes Primary
      Egg Polarity.
AB  - The primordial germ cells (PGCs) of a recently metamorphosed juvenile Synaptula
      hydriformis occur with somatic cells in the germinal epithelium of the gonad. As
      part of the epithelium, PGCs rest on a basal lamina, extend apically towards a
      lumen, are joined to other cells of the epithelium via apicolateral junctions,
      and express apical-basal polarity. Each PGC has an apical flagellum that is
      surrounded by a collar of microvilli. The apicolateral junctions of PGCs consist
      of apical adhering and subapical septate junctions. Hemidesmosomes attach the
      PGCs to the basal lamina. Although the somatic cells form an incomplete layer
      over the PGCs, both the PGCs and somatic cells remain exposed to the apical lumen
      and retain contact with the basal lamina. The peritoneum is the outermost layer
      of the gonad and faces the perivisceral coelom. The epithelial-cell
      characteristics expressed by cells of the peritoneum are identical to those of
      the germinal epithelium. PGCs of S. hydriformis are epithelial flagellated-collar
      cells and express the apical-basal polarity that is typical of epithelial cells.
      The apical-basal polarity of the oocyte, animal-vegetal axis of full-grown eggs,
      and anterior-posterior axis of larvae and adults are all in correspondence. Thus
      the polarity of the germinal epithelium may determine the primary body axis of
      the next generation.

PMID- 29220237
TI  - Antimicrobial Activity of Limulus Blood: Role of C-Reactive Protein (CRP) and
      Limulus Anti-Lipopolysaccharide Factor (LALF).

PMID- 29220238
TI  - Limulus Retinal mRNA Induces Light-Dependent Currents in Xenopus Oocytes.

PMID- 29220239
TI  - Antennal Responses to Hydrodynamic and Tactile Stimuli in the Spiny Lobster
      Panulirus argus.
AB  - The responses of the long, spiny, antennal flagella of the spiny lobster
      Panulirus argus to hydrodynamic and tactile stimuli were investigated.
      Experiments were performed in the dark and included videographic laboratory
      studies of small tethered lobsters (<20 mm carapace length) and nighttime field
      observations of larger, subadult, foraging animals. The antennae are held
      laterally in both tethered and free-ranging animals. Water jets trigger bilateral
      antennal responses in which both flagella are swept forward for rostrally
      directed stimuli, backward for caudal stimuli, and in an intermediate backward
      direction when stimulated laterally. Mean response angles are greater for caudal
      stimuli (17 degrees -48 degrees ) than for rostral stimuli (10 degrees -16
      degrees ), and lobsters exhibit lateralized sensitivity when jets are directed
      from the caudal sector, as indicated by larger ipsilateral responses--up to twice
      the amplitude of contralateral responses in field experiments. Untethered
      lobsters frequently turn the body in the direction of the water jet and tailflip
      away or tailflip without first turning. Tactile stimuli to the lateral edges of
      the antenna, carapace, walking leg, abdomen, and tailfan also trigger primarily
      backward sweeps of the antennae. Only the antennule and medial antennal receptive
      fields yield forward movements, and these elicit smaller responses (mean response
      <= 5 degrees ) than in the backward direction (mean responses up to 15 degrees ).
      Threshold tactile stimuli trigger exclusively ipsilateral responses; thus,
      lateralization is absolute. These results demonstrate that spiny lobsters
      accurately localize mechanosensory stimuli and direct their antennal flagella in
      the perceived direction, a response consistent with a defensive function of the
      antennae in these nonchelate decapods. Overall sensitivity is greatest for
      hydrodynamic stimuli, a result interpreted as being important for the detection
      of and defense against large predatory fish whose nearby movements would generate
      broad, directional, water-current pulses.

PMID- 29220240
TI  - Ionophore-Induced Calcium Waves Activate Unfertilized Zebrafish (Dank rerio)
      Eggs.

PMID- 29220241
TI  - Serotonin Injections Induce Metamorphosis in Larvae of the Gastropod Mollusc
      Ilyanassa obsoleta.
AB  - Bath-applied serotonin (5-HT) induces competent larvae of the marine snail
      Ilyanassa obsoleta to metamorphose. Previously, the mode of action of 5-HT,
      whether as an external ligand or as an internal neurotransmitter, was unknown.
      Larvae were injected with 10-4 M 5-HT and other pharmacological agents to provide
      evidence that serotonergic neurons are necessary for metamorphosis in Ilyanassa
      larvae and that serotonin functions as a neurotransmitter or neuromodulator
      during this process. About 50% of 5-HT-injected animals metamorphose within 48
      hours. Fluoxetine, a 5-HT reuptake inhibitor, and alpha-methyl-5
      hydroxytryptamine (alpham5HT), a 5-HT agonist, were also effective inducers of
      metamorphosis. Gramine (3-[dimethylaminomethyl]indole), a 5-HT antagonist,
      inhibited the inductive activity of 5-HT, while the amino acid gammaaminobutyric
      acid (GABA) resulted in rates of morphological restructuring similar to those of
      controls. Collectively, the results of our experiments support the idea that
      serotonergic neurons are active during larval metamorphosis of Ilyanassa and that
      5-HT does not induce metamorphosis by binding to epidermal chemoreceptors.

PMID- 29220242
TI  - Evolutionary Games That Squids Play: Fighting, Courting, Sneaking, and Mating
      Behaviors Used for Sexual Selection in Loligo pealei.

PMID- 29220243
TI  - Spawning Sound of the Trunkfish, Ostracion meleagris (Ostraciidae).

PMID- 29220244
TI  - Oxygen Production by Dogfish (Mustelus canis) Cornea and Lens Catalase In Situ.

PMID- 29220245
TI  - Developmental Defects in Damselfish (Abudefduf sordidus: Pomacentridae) Embryos
      from Metal Artificial Reefs.

PMID- 29220247
TI  - Ion Fluxes from Skate Retinal Horizontal Cells Measured Using Self-Referencing
      Ion-Selective Electrodes.

PMID- 29220246
TI  - Lead Affects Learning by Hermissenda crassicornis.

PMID- 29220248
TI  - The Temporal Transfer Function of the Limulus Lateral Eye.

PMID- 29220249
TI  - Estimating Denitrification in Sediments of the Parker River Estuary,
      Massachusetts.

PMID- 29220250
TI  - Segmental Organization of Vestibular and Reticular Projections to Spinal and
      Oculomotor Nuclei in the Zebrafish and Goldfish.

PMID- 29220251
TI  - Potentiation of Limulin-Mediated Cytolysis by Thiol Ester-Reacted Forms of
      Limulus alpha2-Macroglobulin: Identification of Functionally Important Domains.

PMID- 29220252
TI  - Tuning in Saccular Afferents of the Toadfish Revealed by the Reverse Correlation
      Method.

PMID- 29220253
TI  - Gas Exchange Rates in the Parker River Estuary, Massachusetts.

PMID- 29220254
TI  - Photochemical and Microbial Processing of Dissolved Organic Matter in Streams and
      Soilwater.

PMID- 29220255
TI  - The Plasma-Based Cytolytic System of the American Horseshoe Crab, Limulus
      polyphemus: Cooperative Interaction of the Sialic Acid-Binding Lectin Limulin and
      Thiol Ester-Reacted alpha2-Macroglobulin.

PMID- 29220256
TI  - Particulate and Dissolved Nitrogen: A Laboratory Study of Transformations in
      Groundwater and Estuarine Samples of the Waquoit Bay Estuarine System.

PMID- 29220257
TI  - Masking Effects of Sulfate upon Microciona Sponge Cell Carbohydrates: A Lectin
      Histochemical Study.

PMID- 29220258
TI  - Chemically Induced Cardiovascular Defects in Developmental Stages of Vertebrates:
      Dose-Response and Phenotypic Comparisons in Medaka and Zebrafish Exposed to Aryl
      Hydrocarbon Receptor Agonists.

PMID- 29220259
TI  - Zebrafish Embryo Monitoring of the Aquatic Environment: Dose-Response Synergism
      Revealed in Combinations of Pollutant Chemical Mixtures.

PMID- 29220260
TI  - Development and Regeneration of Comb Plates in the Ctenophore Mnemiopsis leidyi.

PMID- 29220261
TI  - Shrimp in Waquoit Bay: Effects of Nitrogen Loading on Size and Abundance.

PMID- 29220262
TI  - Selection of Nitrogen-Enriched Macroalgae (Cladophora vagabunda and Gracilaria
      tikvahiae) by the Herbivorous Amphipod Microdeutopus gryllotalpa.

PMID- 29220264
TI  - Myogenic Differentiation of Sea Urchin Secondary Mesenchyme Cells Is Dependent on
      an Intact Extracellular Matrix.

PMID- 29220263
TI  - Selectivity by the Herbivorous Amphipod Microdeutopus gryllotalpa Among Five
      Species of Macroalgae.

PMID- 29220265
TI  - Abundance, Biomass, and Species Richness of Fish Communities in Relation to
      Nitrogen-Loading Rates of Waquoit Bay Estuaries.

PMID- 29220266
TI  - The Origins of Mesoderm in the Equal-Cleaving Nemertean Worm Cerebratulus
      lacteus.

PMID- 29220267
TI  - Assessment of Fish Communities in New England Embayments: Application of the
      Estuarine Biotic Integrity Index.

PMID- 29220268
TI  - Changes in N and C Stable Isotope Signatures of Particulate Organic Matter and
      Ribbed Mussels in Estuaries Subject to Different Nutrient Loading.

PMID- 29220269
TI  - Growth Rates of Ribbed Mussels in Six Estuaries Subject to Different Nutrient
      Loads.

PMID- 29220270
TI  - Podial Particle Picking in Cassidulus caribaearum (Echinodermata: Echinoidea) and
      the Phylogeny of Sea Urchin Feeding Mechanisms.
AB  - Selective particle-picking mechanisms of clypeasteroid echinoids (sand dollars
      and related taxa) are well-known. Those of the extant outgroup to clypeasteroids,
      the cassiduloids (lamp urchins), have not been analyzed to determine the origins
      of this sophisticated feeding mechanism. Cassidulus caribaearum Lamarck, 1801, is
      a small cassiduloid living in the coarse, carbonate sands of protected beaches.
      The total gut contents of 24 specimens of C. caribaearum, representing a full
      size range, were studied. The distribution of particle sizes in this sample was
      not significantly different from that of beach sediment, indicating that C.
      caribaearum is probably not a selective deposit feeder. Juveniles with a test
      length of less than 3.5 mm do not feed, but all echinoids that are at least 5 mm
      long have full, or almost full, guts. The size of the mouth does not limit the
      sizes of particles eaten, regardless of the size of the animal. Allometric
      analyses suggest that podial size is also not a strong predictor of ingested
      particle size. In vivo and histological observations differentiate between the
      test cleansing functions of the spines and ciliary currents and the feeding
      activities of specialized podia. The new role played by accessory podia in food
      collection by C. caribaearum is a synapomorphy for cassiduloids and
      clypeasteroids, whereas the exclusive use of phyllopodia seen in earlier
      irregular echinoids is plesiomorphic.

PMID- 29220271
TI  - Capture of Large Particles by Suspension-Feeding Scaleworm Larvae (Polychaeta:
      Polynoidae).
AB  - Most of the polychaete larvae in which feeding mechanisms have been studied feed
      using an opposed-band mechanism, capturing particles with prototrochal and
      metatrochal ciliary bands and transporting them to the mouth via a food groove.
      However, many other planktotrophic polychaete larvae lack a metatroch and food
      groove and thus must feed in a different way. In this latter group are the larvae
      of polynoid polychaetes, which not only lack a metatroch and food groove but also
      bear a bundle of long cilia (the oral brush) attached near the left side of the
      mouth. In feeding experiments with polystyrene beads and plankton, larvae of the
      polynoid Arctonoe vittata ingested larger particles (up to 60 {mu}m in diameter)
      than those ingested by the opposed-band feeding larvae of the serpulid Serpula
      vermicularis (up to 12 MUm in diameter). Videotaped images of feeding A. vittata
      larvae showed that capture behavior was elicited as particles in a feeding
      current driven by the prototroch approached or contacted the larval episphere.
      Particles on or very near the episphere were disengaged by a recoiling motion of
      the larva and were then moved to the mouth, probably by the oral brush. This
      feeding mechanism may be widespread in the polychaete superfamily Aphroditacea,
      which includes about 10% of extant polychaete species.

PMID- 29220272
TI  - Modified Spiral Cleavage: The Duet Cleavage Pattern and Early Blastomer Fates in
      the Acoel Turbellarian Neochildia fusca.

PMID- 29220273
TI  - Two Kinds of Active Factor in Crab Hatch Water: Ovigerous-Hair Stripping
      Substance (OHSS) and a Proteinase.
AB  - The embryos of intertidal and estuarine crabs are clustered on the ovigerous seta
      of the female, where they are ventilated for 2-4 weeks by the female's abdomen.
      When the embryonic development is complete, hatching occurs and zoea larvae are
      released into the water. This study indicates that the crab hatch water (i.e.,
      the filtered medium into which zoeas were released) contains at least two kinds
      of active substance: OHSS (ovigerous-hair stripping substance) and a proteolytic
      enzyme. Both factors were separated by gel filtration. Powdered fragments of egg
      capsule were digested by proteinase, suggesting that this enzyme actually acts on
      the egg capsule. But this activity was at a very low level compared with casein
      digestion. The proteinase might be digesting the thin, sticky layer enclosing the
      embryo and would not act on the thick, tough layer constituting the main
      component of the egg capsule. Therefore, a proteolysis of such low activity could
      not be expected to cause the egg capsule to rupture.

PMID- 29220274
TI  - Effect of Larval Swimming Duration on Success of Metamorphosis and Size of the
      Ancestrular Lophophore in Bugula neritina (Bryozoa).
AB  - There is a growing realization that events during one portion of an organism's
      life cycle can have both subtle and dramatic effects on other stages in the life
      history. Lethal and sublethal effects associated with the duration of larval
      swimming in marine invertebrates were examined for the bryozoan Bugula neritina.
      Larvae were kept swimming up to a maximum of 28 h at 20 degrees C by exposure to
      continuous bright fluorescent illumination. At 4-h intervals, samples of 20-40
      larvae were removed from bright illumination and were exposed to seawater
      containing 10 mM excess KCI, an inducer of metamorphosis in this species. Over
      the first 12 h of larval swimming, an average of about 90% of the larvae
      initiated and completed metamorphosis; at 16 h, the percentage of larvae
      initiating and completing metamorphosis dropped significantly. By 28 h, about
      half of the larvae were initiating metamorphosis, whereas only one-fifth were
      completing metamorphosis. Larval swimming duration also significantly affected
      the duration of metamorphosis. By 30 h of larval swimming, individuals were
      taking about 25% longer to complete metamorphosis. Compared to ancestrulae that
      developed from larvae that were induced to metamorphose shortly after the onset
      of swimming, those that swam for greater than 8 h had significantly smaller
      lophophores. For example, by 28 h of larval swimming the ancestrular lophophore
      decreased in height, surface area, and volume by about 25%, 40% and 55%,
      respectively. This marked decrease in lophophore size may ultimately affect the
      ability of juveniles to sequester food, compete for space, and attain
      reproductive maturity. Thus, increasing the duration of larval swimming affects
      both metamorphosis and the development of postlarval structures, which may
      ultimately influence colony fitness.

PMID- 29220275
TI  - Effects of Altering pHi and pHo on the Activation of Chaetopterus Eggs.

PMID- 29220277
TI  - Filament Tracking and Casting in American Elvers (Anguilla rostrata).

PMID- 29220276
TI  - Ultrastructure and Transport-Related Enzymes of the Gills and Coxal Gland of the
      Horseshoe Crab Limulus polyphemus.
AB  - The horseshoe crab, Limulus polyphemus, may be unique among marine arthropods in
      that both its book gills and its coxal gland may serve as sites of ion transport.
      We have therefore examined the ultrastructure of these organs, as well as the
      distribution and relative levels of two major transport-related enzymes: the Na+
      + K+ ATPase and carbonic anhydrase (CA). The ventral surface of the central
      region of each lamella shows the typical ultrastructural specializations for ion
      transport: 10 MUm cell thickness, an extensive network of tubules originating
      from infoldings of the basal membrane, and a high density of mitochondria. This
      region also contains high levels of activity of the Na+ + K+ ATPase and CA. The
      distribution of ion transporting epithelium and transport enzymes is identical in
      each of the five gill books. The peripheral region of the lamellae of each gill
      book is specialized for passive gas exchange. The ultrastructural and biochemical
      profile of the coxal gland is similar to that of the central-ventral region of
      the gill. Limulus possesses the same general mechanism of ion regulation seen in
      euryhaline decapod crustaceans, but the structural and functional components are
      uniquely distributed.

PMID- 29220278
TI  - Intracellular pH Measurements During Fertilization of Surf Clam (Spisula
      solidissima) Oocytes.

PMID- 29220279
TI  - Behavior of Purely Chemotactic Robot Lobster Reveals Different Odor Dispersal
      Patterns in the Jet Region and the Patch Field of a Turbulent Plume.

PMID- 29220280
TI  - Obstacles to Flow Produce Distinctive Patterns of Odor Dispersal on a Scale That
      Could be Detected by Marine Animals.

PMID- 29220281
TI  - Orientation Behavior of the Lobster: Responses to Directional Chemical and
      Hydrodynamic Stimulation of the Antennules.

PMID- 29220282
TI  - Inherent Nonrandom Structure of the Pre-Nuclear Envelope Breakdown Calcium Signal
      in Sand Dollar (Echinaracnius parma) Embryos.

PMID- 29220283
TI  - Potential Role of Syntrophins in Regulating Motility of Sperm in the Sea Urchin
      Arbacia punctulata.

PMID- 29220284
TI  - Reversible Alteration of Molluscan Erythrocyte Morphology by a Natural Hemolymph
      Activity.

PMID- 29220285
TI  - Abundance and Age-Specific Growth Rates in Relation to Population Densities of
      Fundulus heteroclitus in Waquoit Bay Estuaries Subject to Different Nitrogen
      Loads.

PMID- 29220287
TI  - Surface-Dwelling Bacteria on the Eggs of Crangon septemspinosa Restrict Infection
      by the Fungus Lagenidium myophilum In Vitro.

PMID- 29220286
TI  - New Evidence for Bacterial Diversity in the Accessory Nidamental Gland of the
      Squid (Loligo pealei).

PMID- 29220288
TI  - Contemporary Sarcoma Diagnosis, Genetics, and Genomics.
AB  - Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis,
      clinical behavior, and treatment. Owing to their rarity and histologic overlap,
      accurate diagnosis of sarcomas can be challenging. Our approach has evolved
      dramatically in the past few decades, where novel insights into the molecular
      pathogenetic basis for sarcomas has dramatically (re)shaped contemporary
      diagnosis, building on a largely morphology- and clinical presentation-based
      strategy. Examples include the introduction of novel immunohistochemical markers
      that serve as surrogates for molecular genetic alterations and identification of
      characteristic molecular alterations. Accordingly, cytogenetic and molecular
      genetic analyses, such as conventional karyotyping, fluorescence in situ
      hybridization, reverse transcription-polymerase chain reaction, and targeted
      sequencing, have increasingly been incorporated into the routine diagnostic work
      up of these neoplasms. For those sarcomas with complex cytogenetic changes that
      lack specific alterations, additional testing is often directed toward
      identifying lines of differentiation and excluding pathognomonic (cyto-)genetic
      alterations. Although some gene rearrangements are diagnostic of particular
      sarcoma types, certain fusion partners, most notably EWSR1, are not tumor
      specific (and may, in fact, also be found in benign tumors). Correlation with
      clinical, radiologic, morphologic, and immunohistochemical findings is
      particularly important in tumors with such rearrangements to establish the
      correct diagnosis, acknowledging the inherent limitations of diagnostic tests.
      The recognition of sarcomas occurring in cancer predisposition syndromes is
      critical, with implications not only for the index patient but also potentially
      for family members, including the need for genetic counseling and sometimes
      particular types of surveillance. Together, contemporary sarcoma evaluation
      involves combining the initial morphologic evaluation with diagnostically
      relevant cytogenetic, molecular, and immunohistochemical testing methods.

PMID- 29220289
TI  - Osteosarcoma, Chondrosarcoma, and Chordoma.
AB  - Osteosarcoma (OS), chondrosarcoma, and chordoma are characterized by multiple
      challenges to the investigator, clinician, and patient. One consequence of their
      rarity among sarcomas, as well as their biologic and clinical heterogeneity, is
      that management guidelines are inadequate to inform the range of individual
      patient-treatment decisions from diagnosis, approaches to surgery, chemotherapy,
      radiotherapy, treatment of recurrence, palliative care, and quality of
      survivorship. Of high-grade sarcomas, OSs are among the most curable, with more
      than two-thirds of patients with localized disease likely to achieve long-term
      survival. Neoadjuvant chemotherapy comprising cisplatin, doxorubicin, and
      methotrexate with intercalated surgery is the standard of care for resectable OS
      in those younger than 40 years. Outcomes for OS presenting with unresectable
      metastases or recurrent disease, or in those older than 40 years are generally
      poor. Overall results have improved little for all patients with OS, and new
      treatments are needed. Surgical resection remains the cornerstone of management
      for chondrosarcoma and chordoma. However, the application of new biologic
      insights to therapeutic development indicates that improved treatments may soon
      be routine for patients with chondrosarcoma and chordoma for whom surgery alone
      is inadequate. For all these uncommon diseases, patients should be offered
      specialist expert care delivered by experienced multidisciplinary teams in high
      volume centers.

PMID- 29220290
TI  - Synovial Sarcoma: Current Concepts and Future Perspectives.
AB  - Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18
      and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United
      States, it most commonly affects young adults between the ages of 15 and 30
      years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a
      combination or epithelioid and sarcomatous components), or poorly differentiated.
      The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable
      (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for
      future therapeutic opportunities. In this review, we focus on the pharmacologic
      management of SS, both in the curative setting, where the standard approach is
      wide surgical excision combined with radiotherapy and/or (neo)adjuvant
      chemotherapy as appropriate, and in the palliative setting. In advanced disease,
      chemotherapy with anthracyclines and/or ifosfamide, trabectedin, or pazopanib has
      been demonstrated to be more active compared with other soft tissue sarcomas. In
      addition, a better understanding of the molecular and immunologic characteristics
      of SS has allowed for the identification of new potential targets and the
      development of novel biology-driven therapies that are all at different stages of
      testing. There include targeted agents, immunotherapy, and metabolic therapies.
      Because the impact of these strategies for improving SS outcome is still limited,
      current and future research is strongly needed to better understand the tumor
      biology, to identify predictive biomarkers, and to improve the outcomes for
      patients with SS.

PMID- 29220291
TI  - Emerging Targeted and Immune-Based Therapies in Sarcoma.
AB  - Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more
      than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable
      disease is still treated with cytotoxic chemotherapy. Recently, our understanding
      of subtype-specific cancer biology has expanded, and it has revealed distinct
      molecular alterations responsible for tumor initiation and progression. These
      findings have motivated the development of targeted therapies that are being
      evaluated in subtype-specific or biomarker-driven clinical trials. Indeed, the
      spectrum of targeted drug development in sarcoma now spans many of the most
      active paradigms in cancer research and includes agents that target cancer
      related vulnerabilities in receptor tyrosine kinases and intracellular signaling
      pathways, epigenetics, metabolism, nuclear-cytoplasmic transport, and many
      others. Our understanding of the sarcoma immune microenvironment and
      heterogeneous mechanisms of tumor immune evasion has also expanded. Although a
      subset of sarcomas appears inflamed and responsive to immune checkpoint blockade
      with programmed death 1 (PD-1) targeted agents, novel immunotherapies and
      combinations likely will be needed for most subtypes. A variety of approaches
      including targeting immune checkpoints other than PD-1; modulating tumor
      associated macrophage phenotype from tumor-promoting to tumor-suppressive status;
      using cellular-based therapies, such as chimeric antigen and high-affinity T-cell
      receptors to deepen the adaptive immune response; and reinvigorating older
      approaches, such as vaccines and oncolytic virus-based treatments-are being
      investigated. The goal of these new approaches is to harness subtype-specific
      insights into cancer and immune biology to bring more effective and less toxic
      treatments to the clinic for the benefit of patients with sarcoma.

PMID- 29220292
TI  - Rhabdomyosarcoma, Ewing Sarcoma, and Other Round Cell Sarcomas.
AB  - Several recent advances have been made in the diagnosis and therapy of malignant
      small round cell tumors that affect children, particularly in rhabdomyosarcoma,
      Ewing sarcoma, and other round cell sarcomas. These advances have provided new
      insights into the pathologic, histologic, and genomic characterization of
      specific tumor subtypes, which has led to the identification of novel therapeutic
      targets and improved stratification of risk. This has, in turn, led to improved
      efficacy in clinical trials of new drug combinations, thereby increasing the
      survival of patients with newly diagnosed and refractory or recurrent round cell
      sarcomas. Here, we review the progress that has been made using genomics to
      identify novel pathologic genomic rearrangements, as well as therapeutic targets.
      We also describe how clinical and molecular factors have helped refine risk
      stratification and therapies that have led to improved clinical outcomes in
      patients with round cell sarcomas.

PMID- 29220293
TI  - Pathologic Angiogenesis of Malignant Vascular Sarcomas: Implications for
      Treatment.
AB  - Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified
      according to the line of differentiation that these neoplastic cells most closely
      resemble: the endothelial cell. Although these malignant vascular sarcomas
      demonstrate immunohistochemical and ultrastructural features typical of this
      lineage, they vary dramatically in presentation and behavior, reflecting
      oncologic mechanisms unique to each. Antineoplastic therapies offer significant
      benefit, but because of the rarity of these cancers, novel therapies are slow to
      develop, and treatment options for these cancers remain limited. Antiangiogenic
      approaches that have shown benefit in other malignancies have not fully realized
      their promise in vascular tumors, suggesting that these tumors do not depend
      entirely on either angiogenic growth factors or on neighboring endothelia that
      are affected by these agents. Nonetheless, translational studies have begun to
      unravel these distinct pathologies, identifying novel translocation products,
      targets of oncogenic virulence factors, and genomic mutations that hijack
      angiogenic signaling and drive malignant growth. Concurrently, an elaborate and
      highly regulated model of angiogenesis and lymphangiogenesis involving vascular
      endothelial growth factor-receptor tyrosine kinase and TGF-beta and Notch
      pathways has emerged that informs treatment of these tumors as well as cancer in
      general. This review summarizes the literature on malignant vascular sarcomas in
      the context of current models of angiogenesis and, in light of recent clinical
      trial data, could help clinician-scientists generate novel therapeutic
      approaches.

PMID- 29220296
TI  - Carcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial
      Mesenchymal Transition.
AB  - In this review, we outline the biology and management of patients with
      carcinosarcomas and related malignancies, which are often included under the
      broader concept of sarcomatoid carcinomas. Carcinosarcomas are unusual tumors
      that are commonly gynecologic in origin, where they are referred to as malignant
      mixed Mullerian tumors, but may appear in any anatomic site. Although a variety
      of hypotheses have been presented as to the biphasic nature of these tumors,
      carcinosarcomas seem to represent the best example in human cancers of the
      concept of epithelial-mesenchymal transition (EMT), in which the two parts of the
      tumor are genomically related to one another, as opposed to the mesenchymal
      component that represents a second neoplasm or (benign) reactive process. In
      general, patients with carcinosarcomas fare worse than patients with carcinomas
      of the same anatomic site. Treatment paradigms for carcinosarcomas generally
      follow those of carcinomas of the same organ site, except where clinical trials
      provide more specific options. Agents that block or reverse EMT are worth
      examination in patients with carcinosarcoma and arguably may be even more
      effective in carcinomas, given evidence of dependence on EMT to generate
      successful metastases. Information about EMT may also inform other phase
      transitions in cancer, such as those between prostate or lung carcinoma and more
      aggressive tumors with neuroendocrine differentiation.

PMID- 29220295
TI  - Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally
      Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.
AB  - Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the
      standard of care in locally advanced head and neck squamous cell cancer
      (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of
      perceived lower toxicity and convenience. However, there is no level 1 evidence
      of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In
      this phase III randomized trial, we assessed the noninferiority of cisplatin 30
      mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3
      weeks, both administered concurrently with curative intent radiotherapy in
      patients with LAHNSCC. The primary end point was locoregional control (LRC);
      secondary end points included toxicity, compliance, response, progression-free
      survival, and overall survival. Results Between 2013 and 2017, we randomly
      assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%)
      received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22
      months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm
      and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of
      14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to
      2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the
      once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P =
      .006). Estimated median progression-free survival in the once-a-week arm was 17.7
      months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6
      months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21.
      Estimated median overall survival in the once-a-week arm was 39.5 months and was
      not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P =
      .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior
      LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and
      should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant
      setting.

PMID- 29220297
TI  - Local Control of Soft Tissue and Bone Sarcomas.
AB  - Sarcomas of soft tissue and bone are mesenchymal malignancies that can arise in
      any anatomic location, most commonly the extremity, retroperitoneum, and trunk.
      Even for lower grade histologic subtypes, local recurrence can cause significant
      morbidity and even disease-related death. Although surgery remains the
      cornerstone of local control, perioperative radiation and systemic therapy are
      often important adjuvants. This review will summarize the current therapeutic
      approaches for local control of soft tissue and bone sarcomas.

PMID- 29220294
TI  - Clinical and Molecular Spectrum of Liposarcoma.
AB  - Liposarcomas are rare malignant tumors of adipocytic differentiation. The
      classification of liposarcomas into four principal subtypes reflects the distinct
      clinical behavior, treatment sensitivity, and underlying biology encompassed by
      these diseases. Increasingly, clinical management decisions and the development
      of investigational therapeutics are informed by an improved understanding of
      subtype-specific molecular pathology. Well-differentiated liposarcoma is the most
      common subtype and is associated with indolent behavior, local recurrence, and
      insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma
      represents focal progression of well-differentiated disease into a more
      aggressive, metastasizing, and fatal malignancy. Both of these subtypes are
      characterized by recurrent amplifications within chromosome 12, resulting in the
      overexpression of disease-driving genes that have been the focus of therapeutic
      targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal
      translocation that results in an oncogenic fusion protein, whereas pleomorphic
      liposarcoma is a karyotypically complex and especially poor-prognosis subtype
      that accounts for less than 10% of liposarcoma diagnoses. A range of novel
      pharmaceutical agents that aim to target liposarcoma-specific biology are under
      active investigation and offer hope of adding to the limited available treatment
      options for recurrent or inoperable disease.

PMID- 29220298
TI  - Gastrointestinal Stromal Tumors.
AB  - GI stromal tumors (GISTs) are neoplasms with a varying malignancy potential
      ranging from virtually indolent tumors to rapidly progressing cancers. GISTs
      occur throughout the intestinal tract, and most harbor an activating mutation in
      either KIT or platelet-derived growth factor A ( PDGFRA). Diagnosis is made using
      immunohistochemistry, but molecular testing with mutation analysis is paramount
      for selection of appropriate therapy. Most small GISTs are cured with surgery.
      Tyrosine kinase inhibitor (TKI) therapy has led to substantial improvements in
      survival, both for patients with localized GIST and those with advanced disease.
      Adjuvant therapy with imatinib benefits patients with a high risk of recurrence,
      with studies suggesting most benefit with at least 3 years of therapy.
      Neoadjuvant imatinib therapy should be considered for patients requiring
      extensive surgery, aiming at shrinking the tumor to allow organ preservation and
      less extensive surgery. The following three TKIs have been approved for the
      management of advanced disease: imatinib, sunitinib, and regorafenib; imatinib is
      usually the best tolerated of the three and the standard first-line treatment.
      TKIs benefit the majority of patients with advanced GIST but have no or limited
      efficacy in patients with the PDGFRA D842V mutation or patients with GIST lacking
      KIT and PDGFRA mutations. Surgery, the mainstay of primary tumor management, also
      plays a role in the advanced disease setting for selected patients, as do some
      other approaches such as palliative radiation therapy. Research continues to
      identify novel therapies, in particular effective agents to treat TKI-refractory
      disease.

PMID- 29220299
TI  - Perioperative Management of Extremity Soft Tissue Sarcomas.
AB  - Surgery is potentially curative for primary nonmetastatic extremity soft tissue
      sarcomas. After surgery alone, patients may remain at risk for local recurrences
      and/or metastatic disease. To reduce the likelihood of a local relapse, the
      addition of radiotherapy (RT) to limb-sparing surgery may result in higher local
      control rates of at least 85%. Generally, it can be stated that local control
      after both preoperative and postoperative RT is comparable, but that preoperative
      RT comes with a more favorable toxicity profile after prolonged follow-up, albeit
      at the cost of a higher wound complication rate. Furthermore, recent data suggest
      that preoperative RT is more cost effective. To reduce the risk of subsequent
      metastatic disease, systemic chemotherapy can be introduced early during the
      primary management of these patients. These systemic chemotherapy regimens can
      also be applied both preoperatively and postoperatively. Finally, with the aim of
      increasing the antitumor response of perioperative RT, these agents may even be
      combined with RT, concurrently and sequentially. While designing new preoperative
      combination regimens, responses should be carefully monitored by both
      sophisticated radiologic and pathologic evaluations. This article reviews all
      these aspects, in addition to limb-sparing surgery.

PMID- 29220300
TI  - Sarcoma: The Merging of Science and Clinical Care.

PMID- 29220301
TI  - Soft Tissue and Uterine Leiomyosarcoma.
AB  - Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma in
      adults and can occur in almost any part of the body. Uterine leiomyosarcoma is
      the most common subtype of uterine sarcoma. Increased awareness of this unique
      histology has allowed for the development of drugs that are specific to LMS and
      has begun to shed light on the similarities and possible unique aspects of soft
      tissue and uterine LMS. In this review, we summarize the current understanding of
      the epidemiology, diagnosis, genomics, and treatment options for LMS.

PMID- 29220302
TI  - Biology and Management of Undifferentiated Pleomorphic Sarcoma, Myxofibrosarcoma,
      and Malignant Peripheral Nerve Sheath Tumors: State of the Art and Perspectives.
AB  - Undifferentiated pleomorphic sarcomas, myxofibrosarcomas, and malignant
      peripheral nerve sheath tumors are characterized by complex genomic
      characteristics and aggressive clinical behavior. Recent advances in the
      understanding of the pathogenesis of these tumors may allow for the development
      of more-effective innovative therapeutic strategies, including immunotherapies.
      This review describes the current knowledge of the epidemiology, clinical
      presentation, treatment, and pathogenesis of these tumors and highlights ongoing
      and future research.

PMID- 29220303
TI  - Locally Aggressive Connective Tissue Tumors.
AB  - In this review, we highlight the complexities of the natural history, biology,
      and clinical management of three intermediate connective tissue tumors: desmoid
      tumor (DT) or aggressive fibromatosis, tenosynovial giant cell tumor (TGCT) or
      diffuse-type pigmented villonodular synovitis (dtPVNS), and giant cell tumor of
      bone (GCTB). Intermediate histologies include tumors of both soft tissue and bone
      origin and are locally aggressive and rarely metastatic. Some common aspects to
      these tumors are that they can be locally infiltrative and/or impinge on critical
      organs, which leads to disfigurement, pain, loss of function and mobility,
      neurovascular compromise, and occasionally life-threatening consequences, such as
      mesenteric, bowel, ureteral, and/or bladder obstruction. DT, PVNS, and GCTB have
      few and recurrent molecular aberrations but, paradoxically, can have variable
      natural histories. A multidisciplinary approach is recommended for optimal
      management. In DT and PVNS, a course of observation may be appropriate, and any
      intervention should be guided by symptoms and/or disease progression. A surgical
      approach should take into consideration the infiltrative nature, difficulty in
      obtaining wide margins, high recurrence rates, acute and chronic surgical
      morbidities, and impact on quality of life. There are similar concerns with
      radiation, which especially relate to optimal field and transformation to high
      grade radiation-associated sarcomas. Systemic therapies must be considered
      carefully in light of acute and chronic toxicities. Although standard and novel
      therapies are promising, many unanswered questions, such as duration of therapy
      and optimal end points to evaluate efficacy of drugs in clinical practice and
      trials, exist. Predictive biomarkers and novel clinical trial end points, such as
      volumetric measurement, magnetic resonance imaging T2 weighted mapping, nuclear
      imaging, and patient-reported outcomes, are in development and will require
      validation in prospective trials.

PMID- 29220304
TI  - The Interaction between Semantic Representation and Episodic Memory.
AB  - The experimental evidence on the interrelation between episodic memory and
      semantic memory is inconclusive. Are they independent systems, different aspects
      of a single system, or separate but strongly interacting systems? Here, we
      propose a computational role for the interaction between the semantic and
      episodic systems that might help resolve this debate. We hypothesize that
      episodic memories are represented as sequences of activation patterns. These
      patterns are the output of a semantic representational network that compresses
      the high-dimensional sensory input. We show quantitatively that the accuracy of
      episodic memory crucially depends on the quality of the semantic representation.
      We compare two types of semantic representations: appropriate representations,
      which means that the representation is used to store input sequences that are of
      the same type as those that it was trained on, and inappropriate representations,
      which means that stored inputs differ from the training data. Retrieval accuracy
      is higher for appropriate representations because the encoded sequences are less
      divergent than those encoded with inappropriate representations. Consistent with
      our model prediction, we found that human subjects remember some aspects of
      episodes significantly more accurately if they had previously been familiarized
      with the objects occurring in the episode, as compared to episodes involving
      unfamiliar objects. We thus conclude that the interaction with the semantic
      system plays an important role for episodic memory.

PMID- 29220305
TI  - Spiking Neural Classifier with Lumped Dendritic Nonlinearity and Binary Synapses:
      A Current Mode VLSI Implementation and Analysis.
AB  - We present a neuromorphic current mode implementation of a spiking neural
      classifier with lumped square law dendritic nonlinearity. It has been shown
      previously in software simulations that such a system with binary synapses can be
      trained with structural plasticity algorithms to achieve comparable
      classification accuracy with fewer synaptic resources than conventional
      algorithms. We show that even in real analog systems with manufacturing
      imperfections (CV of 23.5% and 14.4% for dendritic branch gains and leaks
      respectively), this network is able to produce comparable results with fewer
      synaptic resources. The chip fabricated in [Formula: see text]m complementary
      metal oxide semiconductor has eight dendrites per cell and uses two opposing
      cells per class to cancel common-mode inputs. The chip can operate down to a
      [Formula: see text] V and dissipates 19 nW of static power per neuronal cell and
      [Formula: see text] 125 pJ/spike. For two-class classification problems of high
      dimensional rate encoded binary patterns, the hardware achieves comparable
      performance as software implementation of the same with only about a 0.5%
      reduction in accuracy. On two UCI data sets, the IC integrated circuit has
      classification accuracy comparable to standard machine learners like support
      vector machines and extreme learning machines while using two to five times
      binary synapses. We also show that the system can operate on mean rate encoded
      spike patterns, as well as short bursts of spikes. To the best of our knowledge,
      this is the first attempt in hardware to perform classification exploiting
      dendritic properties and binary synapses.

PMID- 29220306
TI  - Improving Spiking Dynamical Networks: Accurate Delays, Higher-Order Synapses, and
      Time Cells.
AB  - Researchers building spiking neural networks face the challenge of improving the
      biological plausibility of their model networks while maintaining the ability to
      quantitatively characterize network behavior. In this work, we extend the theory
      behind the neural engineering framework (NEF), a method of building spiking
      dynamical networks, to permit the use of a broad class of synapse models while
      maintaining prescribed dynamics up to a given order. This theory improves our
      understanding of how low-level synaptic properties alter the accuracy of high
      level computations in spiking dynamical networks. For completeness, we provide
      characterizations for both continuous-time (i.e., analog) and discrete-time
      (i.e., digital) simulations. We demonstrate the utility of these extensions by
      mapping an optimal delay line onto various spiking dynamical networks using
      higher-order models of the synapse. We show that these networks nonlinearly
      encode rolling windows of input history, using a scale invariant representation,
      with accuracy depending on the frequency content of the input signal. Finally, we
      reveal that these methods provide a novel explanation of time cell responses
      during a delay task, which have been observed throughout hippocampus, striatum,
      and cortex.

PMID- 29220307
TI  - From Winner-Takes-All to Winners-Share-All: Exploiting the Information Capacity
      in Temporal Codes.
AB  - In this letter, we have implemented and compared two neural coding algorithms in
      the networks of spiking neurons: Winner-takes-all (WTA) and winners-share-all
      (WSA). Winners-Share-All exploits the code space provided by the temporal code by
      training a different combination of [Formula: see text] out of [Formula: see
      text] neurons to fire together in response to different patterns, while WTA uses
      a one-hot-coding to respond to distinguished patterns. Using WSA, the maximum
      value of [Formula: see text] in order to maximize information capacity using
      [Formula: see text] output neurons was theoretically determined and utilized. A
      small proof-of-concept classification problem was applied to a spiking neural
      network using both algorithms to classify 14 letters of English alphabet with an
      image size of 15 [Formula: see text] 15 pixels. For both schemes, a modified
      spike-timing-dependent-plasticity (STDP) learning rule has been used to train the
      spiking neurons in an unsupervised fashion. The performance and the number of
      neurons required to perform this computation are compared between the two
      algorithms. We show that by tolerating a small drop in performance accuracy (84%
      in WSA versus 91% in WTA), we are able to reduce the number of output neurons by
      more than a factor of two. We show how the reduction in the number of neurons
      will increase as the number of patterns increases. The reduction in the number of
      output neurons would then proportionally reduce the number of training
      parameters, which requires less memory and hence speeds up the computation, and
      in the case of neuromorphic implementation on silicon, would take up much less
      area.

PMID- 29220308
TI  - Learning Midlevel Auditory Codes from Natural Sound Statistics.
AB  - Interaction with the world requires an organism to transform sensory signals into
      representations in which behaviorally meaningful properties of the environment
      are made explicit. These representations are derived through cascades of neuronal
      processing stages in which neurons at each stage recode the output of preceding
      stages. Explanations of sensory coding may thus involve understanding how low
      level patterns are combined into more complex structures. To gain insight into
      such midlevel representations for sound, we designed a hierarchical generative
      model of natural sounds that learns combinations of spectrotemporal features from
      natural stimulus statistics. In the first layer, the model forms a sparse
      convolutional code of spectrograms using a dictionary of learned spectrotemporal
      kernels. To generalize from specific kernel activation patterns, the second layer
      encodes patterns of time-varying magnitude of multiple first-layer coefficients.
      When trained on corpora of speech and environmental sounds, some second-layer
      units learned to group similar spectrotemporal features. Others instantiate
      opponency between distinct sets of features. Such groupings might be instantiated
      by neurons in the auditory cortex, providing a hypothesis for midlevel neuronal
      computation.

PMID- 29220309
TI  - Quantifying Strength of Chaos in the Population Firing Rate of Neurons.
AB  - In this study, I considered quantifying the strength of chaos in the population
      firing rate of a pulse-coupled neural network. In particular, I considered the
      dynamics where the population firing rate is chaotic and the firing of each
      neuron is stochastic. I calculated a time histogram of firings to show the
      variation in the population firing rate over time. To smooth this histogram, I
      used Bayesian adaptive regression splines and a gaussian filter. The nonlinear
      prediction method, based on reconstruction, was applied to a sequence of
      interpeak intervals in the smoothed time histogram of firings. I propose the use
      of the sum of nonlinearity as a quantifier of the strength of chaos. When
      applying this method to the firings of a pulse-coupled neural network, the sum of
      nonlinearity was seen to satisfy three properties for quantifying the strength of
      chaos. First, it can be calculated from spiking data alone. Second, it takes
      large values when applied to firings that are confirmed, theoretically or
      numerically, to be chaotic. Third, it reflects the strength of chaos of the
      original dynamics.

PMID- 29220310
TI  - Direct and indirect relationships of physical fitness, weight status, and
      learning duration to academic performance in Japanese schoolchildren.
AB  - The purpose of this study was to determine, using structural equation modelling
      (SEM), the direct and indirect influence of daily behaviours (i.e.
      exercise/learning durations), weight status, and physical fitness on academic
      performance among seventh-grade schoolchildren, after controlling for
      socioeconomic status. We analysed cross-sectional data from 274 schoolchildren
      (159 males and 115 females; 12-13 years old). Academic performance was assessed
      using the total grade points in eight academic subjects. Physical fitness was
      evaluated using the total score of eight physical fitness tests and weight status
      using body mass index. The daily behaviours and socioeconomic status were
      assessed by the questionnaire. The SEM showed an adequate fit to the data (chi2 =
      0.684, p = .710, RMSEA = .000). Physical fitness and learning durations had
      direct effects on academic performance (beta = .301, p < .001; beta = .132, p =
      .037, respectively) after controlling for confounders. Healthy weight status and
      exercise habits positively indirectly influenced academic performance via
      physical fitness. These findings suggest that, independent of socioeconomic
      status and learning durations, exercise habits and maintaining healthy weight
      status may indirectly contribute to academic success via better physical fitness
      in children.

PMID- 29220312
TI  - L0 -Regularized Image Downscaling.
AB  - In this paper, we propose a novel -regularized optimization framework for image
      downscaling. The optimization is driven by two -regularized priors. The first
      prior, gradient-ratio prior, is based on the observation that the number of edges
      in the downscaled image is approximately inverse square proportional to the
      downscaling factor. By introducing norm sparsity to the gradient ratio, the
      downscaled image is able to preserve the most salient edges as well as the visual
      perception of the original image. The second prior, downsampling prior, is to
      constrain the downsampling matrix so that pixels of the downscaled image are
      estimated according to those optimal neighboring pixels. Extensive experiments on
      the Urban100 and BSDS500 data sets show that the proposed algorithm achieves
      superior performance over the state-of-the-arts, in terms of both quality and
      robustness.

PMID- 29220311
TI  - Quantifying the effects of acute hypoxic exposure on exercise performance and
      capacity: A systematic review and meta-regression.
AB  - OBJECTIVE: To quantify the effects of acute hypoxic exposure on exercise capacity
      and performance, which includes continuous and intermittent forms of exercise.
      DESIGN: A systematic review was conducted with a three-level mixed effects meta
      regression. The ratio of means method was used to evaluate main effects and
      moderators providing practical interpretations with percentage change. DATA
      SOURCES: A systemic search was performed using three databases (Google scholar,
      PubMed and SPORTDiscus). Eligibility criteria for selecting studies: Inclusion
      was restricted to investigations that assessed exercise performance (time trials
      (TTs), sprint and intermittent exercise tests) and capacity (time to exhaustion
      test, TTE) with acute hypoxic (<24 h) exposure and a normoxic comparator.
      RESULTS: Eighty-two outcomes from 53 studies (N = 798) were included in this
      review. The results show an overall reduction in exercise performance/capacity 
      17.8 +/- 3.9% (95% CI -22.8% to -11.0%), which was significantly moderated by 
      6.5 +/- 0.9% per 1000 m altitude elevation (95% CI -8.2% to -4.8%) and oxygen
      saturation (-2.0 +/- 0.4%; 95% CI -2.9% to -1.2%). TT (-16.2 +/- 4.3%; 95% CI 
      22.9% to -9%) and TTE (-44.5 +/- 6.9%; 95% CI -51.3% to -36.7%) elicited a
      negative effect, whilst indicating a quadratic relationship between hypoxic
      magnitude and both TTE and TT performance. Furthermore, exercise less than 2 min
      exhibited no ergolytic effect from acute hypoxia. Summary/Conclusion: This review
      highlights the ergolytic effect of acute hypoxic exposure, which is curvilinear
      for TTE and TT performance with increasing hypoxic levels, but short duration
      intermittent and sprint exercise seem to be unaffected.

PMID- 29220313
TI  - How Does the Low-Rank Matrix Decomposition Help Internal and External Learnings
      for Super-Resolution.
AB  - Wisely utilizing the internal and external learning methods is a new challenge in
      super-resolution problem. To address this issue, we analyze the attributes of two
      methodologies and find two observations of their recovered details: 1) they are
      complementary in both feature space and image plane and 2) they distribute
      sparsely in the spatial space. These inspire us to propose a low-rank solution
      which effectively integrates two learning methods and then achieves a superior
      result. To fit this solution, the internal learning method and the external
      learning method are tailored to produce multiple preliminary results. Our
      theoretical analysis and experiment prove that the proposed low-rank solution
      does not require massive inputs to guarantee the performance, and thereby
      simplifying the design of two learning methods for the solution. Intensive
      experiments show the proposed solution improves the single learning method in
      both qualitative and quantitative assessments. Surprisingly, it shows more
      superior capability on noisy images and outperforms state-of-the-art methods.

PMID- 29220314
TI  - Random Access Memories: A New Paradigm for Target Detection in High Resolution
      Aerial Remote Sensing Images.
AB  - We propose a new paradigm for target detection in high resolution aerial remote
      sensing images under small target priors. Previous remote sensing target
      detection methods frame the detection as learning of detection model + inference
      of class-label and bounding-box coordinates. Instead, we formulate it from a
      Bayesian view that at inference stage, the detection model is adaptively updated
      to maximize its posterior that is determined by both training and observation. We
      call this paradigm "random access memories (RAM)." In this paradigm, "Memories"
      can be interpreted as any model distribution learned from training data and
      "random access" means accessing memories and randomly adjusting the model at
      detection phase to obtain better adaptivity to any unseen distribution of test
      data. By leveraging some latest detection techniques e.g., deep Convolutional
      Neural Networks and multi-scale anchors, experimental results on a public remote
      sensing target detection data set show our method outperforms several other state
      of the art methods. We also introduce a new data set "LEarning, VIsion and Remote
      sensing laboratory (LEVIR)", which is one order of magnitude larger than other
      data sets of this field. LEVIR consists of a large set of Google Earth images,
      with over 22 k images and 10 k independently labeled targets. RAM gives
      noticeable upgrade of accuracy (an mean average precision improvement of 1% ~ 4%)
      of our baseline detectors with acceptable computational overhead.

PMID- 29220315
TI  - Background Modeling by Stability of Adaptive Features in Complex Scenes.
AB  - The single-feature-based background model often fails in complex scenes, since a
      pixel is better described by several features, which highlight different
      characteristics of it. Therefore, the multi-feature-based background model has
      drawn much attention recently. In this paper, we propose a novel multi-feature
      based background model, named stability of adaptive feature (SoAF) model, which
      utilizes the stabilities of different features in a pixel to adaptively weigh the
      contributions of these features for foreground detection. We do this mainly due
      to the fact that the features of pixels in the background are often more stable.
      In SoAF, a pixel is described by several features and each of these features is
      depicted by a unimodal model that offers an initial label of the target pixel.
      Then, we measure the stability of each feature by its histogram statistics over a
      time sequence and use them as weights to assemble the aforementioned unimodal
      models to yield the final label. The experiments on some standard benchmarks,
      which contain the complex scenes, demonstrate that the proposed approach achieves
      promising performance in comparison with some state-of-the-art approaches.

PMID- 29220316
TI  - Edge-Based Defocus Blur Estimation With Adaptive Scale Selection.
AB  - Objects that do not lie at the focal distance of a digital camera generate
      defocused regions in the captured image. This paper presents a new edge-based
      method for spatially varying defocus blur estimation using a single image based
      on reblurred gradient magnitudes. The proposed approach initially computes a
      scale-consistent edge map of the input image and selects a local reblurring scale
      aiming to cope with noise, edge mis-localization, and interfering edges. An
      initial blur estimate is computed at the detected scale-consistent edge points
      and a novel connected edge filter is proposed to smooth the sparse blur map based
      on pixel connectivity within detected edge contours. Finally, a fast guided
      filter is used to propagate the sparse blur map through the whole image.
      Experimental results show that the proposed approach presents a very good
      compromise between estimation error and running time when compared with the state
      of-the-art methods. We also explore our blur estimation method in the context of
      image deblurring, and show that metrics typically used to evaluate blur
      estimation may not correlate as expected with the visual quality of the deblurred
      image.

PMID- 29220317
TI  - No-Reference Image Quality Assessment by Wide-Perceptual-Domain Scorer Ensemble
      Method.
AB  - A no-reference (NR) learning-based approach to assess image quality is presented
      in this paper. The devised features are extracted from wide perceptual domains,
      including brightness, contrast, color, distortion, and texture. These features
      are used to train a model (scorer) which can predict scores. The scorer selection
      algorithms are utilized to help simplify the proposed system. In the final stage,
      the ensemble method is used to combine the prediction results from selected
      scorers. Two multiple-scale versions of the proposed approach are also presented
      along with the single-scale one. They turn out to have better performances than
      the original single-scale method. Because of having features from five different
      domains at multiple image scales and using the outputs (scores) from selected
      score prediction models as features for multi-scale or cross-scale fusion (i.e.,
      ensemble), the proposed NR image quality assessment models are robust with
      respect to more than 24 image distortion types. They also can be used on the
      evaluation of images with authentic distortions. The extensive experiments on
      three well-known and representative databases confirm the performance robustness
      of our proposed model.

PMID- 29220318
TI  - Detection and Separation of Smoke From Single Image Frames.
AB  - This paper proposes novel methods for detecting and separating smoke from a
      single image frame. Specifically, an image formation model is derived based on
      the atmospheric scattering models. The separation of a frame into quasi-smoke and
      quasi-background components is formulated as convex optimization that solves a
      sparse representation problem using dual dictionaries for the smoke and
      background components, respectively. A novel feature is constructed as a
      concatenation of the respective sparse coefficients for detection. In addition, a
      method based on the concept of image matting is developed to separate the true
      smoke and background components from the smoke detection results. Extensive
      experiments on detection were conducted and the results showed that the proposed
      feature significantly outperforms existing features for smoke detection. In
      particular, the proposed method is able to differentiate smoke from other
      challenging objects (e.g. fog/haze, cloud, and so on) with similar visual
      appearance in a gray-scale frame. Experiments on smoke separation also
      demonstrated that the proposed separation method can effectively
      estimate/separate the true smoke and background components.

PMID- 29220319
TI  - POI Summarization by Aesthetics Evaluation From Crowd Source Social Media.
AB  - Place-of-Interest (POI) summarization by aesthetics evaluation can recommend a
      set of POI images to the user and it is significant in image retrieval. In this
      paper, we propose a system that summarizes a collection of POI images regarding
      both aesthetics and diversity of the distribution of cameras. First, we generate
      visual albums by a coarse-to-fine POI clustering approach and then generate 3D
      models for each album by the collected images from social media. Second, based on
      the 3D to 2D projection relationship, we select candidate photos in terms of the
      proposed crowd source saliency model. Third, in order to improve the performance
      of aesthetic measurement model, we propose a crowd-sourced saliency detection
      approach by exploring the distribution of salient regions in the 3D model. Then,
      we measure the composition aesthetics of each image and we explore crowd source
      salient feature to yield saliency map, based on which, we propose an adaptive
      image adoption approach. Finally, we combine the diversity and the aesthetics to
      recommend aesthetic pictures. Experimental results show that the proposed POI
      summarization approach can return images with diverse camera distributions and
      aesthetics.

PMID- 29220320
TI  - Virtual View Synthesis for Free Viewpoint Video and Multiview Video Compression
      using Gaussian Mixture Modelling.
AB  - High quality virtual views need to be synthesized from adjacent available views
      for free viewpoint video and multiview video coding (MVC) to provide users with a
      more realistic 3D viewing experience of a scene. View synthesis techniques suffer
      from poor rendering quality due to holes created by occlusion and rounding
      integer error through warping. To remove the holes in the virtual view, the
      existing techniques use spatial and temporal correlation in intra/inter-view
      images and depth maps. However, they still suffer quality degradation in the
      boundary region of foreground and background areas due to the low spatial
      correlation in texture images and low correspondence in inter-view depth maps. To
      overcome the above-mentioned limitations, we use a number of models in the
      Gaussian mixture modeling (GMM) to separate background and foreground pixels in
      our proposed technique. Here, the missing pixels introduced from the warping
      process are recovered by the adaptive weighted average of the pixel intensities
      from the corresponding GMM model(s) and warped image. The weights vary with time
      to accommodate the changes due to a dynamic background and the motions of the
      moving objects for view synthesis. We also introduce an adaptive strategy to
      reset the GMM modeling if the contributions of the pixel intensities drop
      significantly. Our experimental results indicate that the proposed approach
      provides 5.40-6.60-dB PSNR improvement compared with the relevant methods. To
      verify the effectiveness of the proposed view synthesis technique, we use it as
      an extra reference frame in the motion estimation for MVC. The experimental
      results confirm that the proposed view synthesis is able to improve PSNR by 3.15
      5.13 dB compared with the conventional three reference frames.

PMID- 29220321
TI  - End-to-End Blind Image Quality Assessment Using Deep Neural Networks.
AB  - We propose a multi-task end-to-end optimized deep neural network (MEON) for blind
      image quality assessment (BIQA). MEON consists of two sub-networks-a distortion
      identification network and a quality prediction network-sharing the early layers.
      Unlike traditional methods used for training multi-task networks, our training
      process is performed in two steps. In the first step, we train a distortion type
      identification sub-network, for which large-scale training samples are readily
      available. In the second step, starting from the pre-trained early layers and the
      outputs of the first sub-network, we train a quality prediction sub-network using
      a variant of the stochastic gradient descent method. Different from most deep
      neural networks, we choose biologically inspired generalized divisive
      normalization (GDN) instead of rectified linear unit as the activation function.
      We empirically demonstrate that GDN is effective at reducing model
      parameters/layers while achieving similar quality prediction performance. With
      modest model complexity, the proposed MEON index achieves state-of-the-art
      performance on four publicly available benchmarks. Moreover, we demonstrate the
      strong competitiveness of MEON against state-of-the-art BIQA models using the
      group maximum differentiation competition methodology.

PMID- 29220322
TI  - Effect of Aggregation Operators on Network-Based Disease Gene Prioritization: A
      Case Study on Blood Disorders.
AB  - Owing to the innate noise in the biological data sources, a single source or a
      single measure do not suffice for an effective disease gene prioritization. So,
      the integration of multiple data sources or aggregation of multiple measures is
      the need of the hour. The aggregation operators combine multiple related data
      values to a single value such that the combined value has the effect of all the
      individual values. In this paper, an attempt has been made for applying the fuzzy
      aggregation on the network-based disease gene prioritization and investigate its
      effect under noise conditions. This study has been conducted for a set of 15
      blood disorders by fusing four different network measures, computed from the
      protein interaction network, using a selected set of aggregation operators and
      ranking the genes on the basis of the aggregated value. The aggregation operator
      based rankings have been compared with the "Random walk with restart" gene
      prioritization method. The impact of noise has also been investigated by adding
      varying proportions of noise to the seed set. The results reveal that for all the
      selected blood disorders, the Mean of Maximal operator has relatively
      outperformed the other aggregation operators for noisy as well as non-noisy data.

PMID- 29220323
TI  - Grasp Performance of a Soft Synergy-Based Prosthetic Hand: A Pilot Study.
AB  - Current prosthetic hands are frequently rejected in part due to limited
      functionality and versatility. We assessed the feasibility of a novel prosthetic
      hand, the SoftHand Pro (SHP), whose design combines soft robotics and hand
      postural synergies. Able-bodied subjects ( ) tracked cursor motion by opening and
      closing the SHP and performed a grasp-lift-hold-release (GLHR) task with a
      sensorized cylindrical object of variable weight. The SHP control was driven by
      electromyographic (EMG) signals from two antagonistic muscles. Although the time
      to perform the GLHR task was longer for the SHP than native hand for the first
      few trials (10.2 +/- 1.4 s and 2.13 +/- 0.09 s, respectively), performance was
      much faster on subsequent trials (~5 s). The SHP steady-state grip force was
      significantly modulated as a function of object weight ( ). For the native hand,
      however, peak and steady-state grip forces were modulated to a greater extent
      (+68% and +91%, respectively). These changes were mediated by the modulation of
      EMG amplitude and co-contraction. These data suggest that the SHP has a promise
      for prosthetic applications and point-to-design modifications that could improve
      the SHP.

PMID- 29220324
TI  - Performance of Optimized Prosthetic Ankle Designs That Are Based on a Hydraulic
      Variable Displacement Actuator (VDA).
AB  - Current energy storage and return prosthetic feet only marginally reduce the cost
      of amputee locomotion compared with basic solid ankle cushioned heel feet,
      possibly due to their lack of push-off at the end of stance. To the best of our
      knowledge, a prosthetic ankle that utilizes a hydraulic variable displacement
      actuator (VDA) to improve push-off performance has not previously been proposed.
      Therefore, here we report a design optimization and simulation feasibility study
      for a VDA-based prosthetic ankle. The proposed device stores the eccentric ankle
      work done from heel strike to maximum dorsiflexion in a hydraulic accumulator and
      then returns the stored energy to power push-off. Optimization was used to
      establish the best spring characteristic and gear ratio between ankle and VDA.
      The corresponding simulations show that, in level walking, normal push-off is
      achieved and, per gait cycle, the energy stored in the accumulator increases by
      22% of the requirements for normal push-off. Although the results are promising,
      there are many unanswered questions and, for this approach to be a success, a new
      miniature, low-losses, and lightweight VDA would be required that is half the
      size of the smallest commercially available device.

PMID- 29220325
TI  - Direction Modulation of Muscle Synergies in a Hand-Reaching Task.
AB  - Functional tasks of the upper extremity can be executed by a variety of muscular
      patterns, independent of the direction, speed and load of the task. This large
      number of degrees of freedom imposes a significant control burden on the CNS.
      Previous studies suggested that the human cortex synchronizes a discrete number
      of neural functional units within the brainstem and spinal cord, i.e. muscle
      synergies, by linearly combining them to execute a great repertoire of movements.
      Further exploring this control mechanism, we aim to study whether a single set of
      muscle synergies might be generalized to express movements in different
      directions. This was implemented by using a modified version of the non-negative
      matrix factorization algorithm on EMG data sets of the upper extremity of healthy
      people. Our twelve participants executed hand-reaching movements in multiple
      directions. Muscle synergies that were extracted from movements to the center of
      the reaching space could be generalized to synergies for other movement
      directions. This finding was also supported by the application of a weighted
      correlation matrix, the similarity index and the results of the K-means cluster
      analysis. This might reinforce the notion that the CNS flexibly combines a single
      set of small number of synergies in different amplitudes to modulate movement for
      different directions.

PMID- 29220326
TI  - A Portable Ultrasound System for Non-Invasive Ultrasonic Neuro-Stimulation.
AB  - Fundamental insights into the function of the neural circuits often follows from
      the advances in methodologies and tools for neuroscience. Electrode- and optical-
      based stimulation methods have been used widely for neuro-modulation with high
      resolution. However, they are suffering from inherent invasive surgical
      procedure. Ultrasound has been proved as a promising technology for neuro
      stimulation in a non-invasive manner. However, no portable ultrasound system has
      been developed particularly for neuro-stimulation. The utilities used currently
      are assembled by traditional functional generator, power amplifier, and general
      transducer, therefore, resulting in lack of flexibility. This paper presents a
      portable system to achieve ultrasonic neuro-stimulation to satisfy various
      studies. The system incorporated a high voltage waveform generator and a matching
      circuit that were optimized for neuro-stimulation. A new switching mode power
      amplifier was designed and fabricated. The noise generated by the power amplifier
      was reduced (about 30 dB), and the size and weight were smaller in contrast with
      commercial equipment. In addition, a miniaturized ultrasound transducer was
      fabricated using Pb(Mg1/3Nb2/3)O3-PbTiO3(PMN-PT) 1-3 composite single crystal for
      the improved ultrasonic performance. The spatial peak temporal average pressure
      was higher than 250 kPa in the range of 0.5-5 MHz. In vitro and in vivo studies
      were conducted to show the performance of the system.

PMID- 29220328
TI  - Message from the Editor-in-Chief.

PMID- 29220327
TI  - Self-Paced Operation of a Wheelchair Based on a Hybrid Brain-Computer Interface
      Combining Motor Imagery and P300 Potential.
AB  - This paper presents a hybrid brain-computer interface (BCI) that combines motor
      imagery (MI) and P300 potential for the asynchronous operation of a brain
      controlled wheelchair whose design is based on a Mecanum wheel. This paradigm is
      completely user-centric. By sequentially performing MI tasks or paying attention
      to P300 flashing, the user can use eleven functions to control the wheelchair:
      move forward/backward, move left/right, move left45/right45,
      accelerate/decelerate, turn left/right, and stop. The practicality and
      effectiveness of the proposed approach were validated in eight subjects, all of
      whom achieved good performance. The preliminary results indicated that the
      proposed hybrid BCI system with different mental strategies operating
      sequentially is feasible and has potential applications for practical self-paced
      control.

PMID- 29220329
TI  - Preface.

PMID- 29220332
TI  - PreScription: Issues with the NAMS 2017 Hormone Therapy Position Statement.

PMID- 29220331
TI  - Regenerative potential of secretome from dental stem cells: a systematic review
      of preclinical studies.
AB  - Injury to tissues is a major clinical challenge due to the limited regenerative
      capacity of endogenous cells. Stem cell therapy is evolving rapidly as an
      alternative for tissue regeneration. However, increasing evidence suggests that
      the regenerative ability of stem cells is mainly mediated by paracrine actions of
      secretome that are generally secreted by the cells. We aimed to systematically
      evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo
      animal models of various tissue defects. A total of 15 eligible studies was
      included by searching Pubmed, Scopus and Medline databases up to August 2017. The
      risk of bias was assessed using the Systematic Review Centre for Laboratory
      Animal Experimentation risk of bias tool. Of 15 studies, seven reported the
      therapeutic benefit of the conditioned medium on neurological diseases and three
      reported on joint/bone-related defects. Two interventions were on liver diseases,
      whereas the remaining three addressed myocardial infarction and reperfusion, lung
      injury and diabetes. Nine studies were performed using mouse models and the
      remaining six studies used rat models. The methodological quality of the studies
      was low, as most of the key elements required in reports of preclinical studies
      were not reported. The findings of this review suggested that conditioned medium
      from DSCs improved tissue regeneration and functional recovery. This current
      review strengthens the therapeutic benefit of cell-free product for tissue repair
      in animal models. A well-planned study utilizing validated outcome measures and
      long-term safety studies are required for possible translation to clinical
      trials.

PMID- 29220333
TI  - Feline Transdermal Formulation Considerations.
AB  - Transdermal delivery of drugs is comparatively new in feline patients. However,
      transdermal formulations can be a desirable option for treating feline patients
      that are not willing participants to medication administration. However,
      achieving drug penetration across the skin is not always easy, and there are a
      wide variety of variables that can further affect penetration. This, coupled with
      a lack of studies, make transdermal administration an unknown with regards to
      efficacy and safety for many drugs. This article focuses on drugs that are
      administered transdermally with the intent of producing systemic effects.

PMID- 29220334
TI  - Orodispersible Films for Compounding Pharmacies.
AB  - Orodispersible film can be defined as a solid pharmaceutical form intended for
      the delivery and rapid local or systemic release of active ingredients,
      consisting of a water-soluble polymer film that hydrates rapidly, adhering and
      dissolving immediately when placed on the tongue or in the oral cavity (oral,
      palatal, gingival, lingual, or sublingual), without the need for water
      administration or mastication. Due to its outstanding importance in cases of
      emergency, practicality of use by patients in transit, and high adherence,
      orodispersible film has evolved in popularity and success among consumers. It is
      a promising dosage form for compounding pharmacies, as simpler technologies are
      being developed to make the compound process easier and faster for the
      pharmacist. This article aims to explore some of the basics on orodispersible
      film and the main possible preparations to be developed in compounding pharmacies
      worldwide.

PMID- 29220330
TI  - Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and
      Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs)
      Study.
AB  - BACKGROUND: The optimal timing to administer non-vitamin K oral anticoagulants
      (NOACs) in patients with acute ischemic stroke and atrial fibrillation is
      unclear. This prospective observational multicenter study evaluated the rates of
      early recurrence and major bleeding (within 90 days) and their timing in patients
      with acute ischemic stroke and atrial fibrillation who received NOACs for
      secondary prevention. METHODS AND RESULTS: Recurrence was defined as the
      composite of ischemic stroke, transient ischemic attack, and symptomatic systemic
      embolism, and major bleeding was defined as symptomatic cerebral and major
      extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%)
      were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with
      apixaban. Patients who received dabigatran were younger and had lower admission
      National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2
      VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had
      early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence
      and major bleeding were, respectively, 1.8% and 0.5% in patients receiving
      dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in
      those receiving apixaban. Patients who initiated NOACs within 2 days after acute
      stroke had a composite rate of recurrence and major bleeding of 12.4%; composite
      rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for
      those who initiated >14 days after acute stroke. CONCLUSIONS: In patients with
      acute ischemic stroke and atrial fibrillation, treatment with NOACs was
      associated with a combined 5% rate of ischemic embolic recurrence and severe
      bleeding within 90 days.

PMID- 29220336
TI  - Join the Partnership for Personalized Prescriptions (P3) Advocacy Effort!

PMID- 29220335
TI  - Features of Pharmaceutical Compounding in the Republic of Tajikistan.
AB  - Despite the deep assortment of finished pharmaceutical products and the reduction
      in the number of compounding and hospital pharmacies in the Republic of
      Tajikistan, the need for extemporal medicinal products is still preserved and
      remains relevant. This article discusses the practice of compounding in the
      Republic of Tajikistan. History, laws, limits, regulatory institutions, protocols
      for compounding pharmacy set up, challenges, equipment, extemporaneous
      formulations, quality control, and storage within regulatory framework are
      discussed.

PMID- 29220337
TI  - Basics of Compounding: Hot Melt Extrusion.
AB  - Hot Melt Extrusion, a production process that has been around for quite some
      time, has the ability to produce innovative compounds not previously achievable
      with conventional methods. However, many variables need to be considered prior to
      production. The use of small-scale extruders and 3D printers provides compounders
      a pathway for developing new dosage forms at a minimal cost while initial
      research is being completed. This article discusses the uses of Hot Melt
      Extrusion, the equipment used, the current and future applications, and the
      challenges with the technology.

PMID- 29220338
TI  - Basics of Compounding: Compounding Irrigation Solutions for Sterile and
      Nonsterile Preparations.
AB  - Compounding pharmacists are sometimes called upon to prepare irrigation
      solutions, especially in the hospital or clinical setting. Irrigations are
      indicated for washing or bathing surgical incisions, wounds, and body tissues,
      including body cavities. Some irrigation solutions coming in contact with exposed
      tissue, must meet stringent requirements of sterility and bacterial endotoxins.
      Compounded irrigation solutions may involve wound(s), the bladder, and also may
      be for ophthalmic, otic, and nasal application. Some vaginal
      douches/instillations and rectal solutions may also be used as irrigations. As
      with any medication administered to the body or used on body tissues, there are
      requirements, and these may vary depending on the type of irrigation solution
      involved.

PMID- 29220339
TI  - To Flavor or Not to Flavor Extemporaneous Omeprazole Liquid.
AB  - Omeprazole is a proton pump inhibitor used to treat the symptoms of gastro
      esophageal reflux disease, ulcers, excess stomach acid, infection with
      Helicobacter pylori, and to control the gastric side effects of various drugs.
      The approved dosage forms in the U.S. are powder in compounding kits, delayed
      release granules for oral suspension, oral delayed-release tablets, and oral
      delayed-release capsules. An extemporaneously compounded unsweetened oral liquid
      method, published in the International Journal of Pharmaceutical Compounding, was
      found to be commonly used by pharmacists. This project investigated the
      robustness of the compendium omeprazole high-performance liquid chromatographic
      assay in evaluating an oral liquid made from commercial delayed-release pellets,
      the potency of extemporaneously compounded solutions having a 1.125% v/v flavored
      versus unflavored samples stored at controlled cold temperatures at different
      time points, and examining the absorption spectrum of the flavoring agent. As
      part of the study, stability-indication testing was also conducted. The studies
      indicate that the chromatographic area under the plasma concentration-time curve
      of both study groups remained over 90% of the label claim during the follow-up
      period. The flavor did not significantly impact the pH of the oral liquid. This
      study further identified (1) an increase in resilient foam formation in the
      flavored liquid, potentially hindering dosing accuracy, (2) omeprazole is
      oxidized easily by 3% hydrogen peroxide, and (3) flavoring agent absorbs in an
      ultraviolet visible spectroscopy spectral range often used in assay detectors for
      quantification of drug molecules, and could interfere with assay protocols of the
      same.

PMID- 29220340
TI  - Validation of the Technological Process of the Preparation "Milk by Vidal".
AB  - Validation was performed on the technological process of the compounded
      preparation "Milk by Vidal" in accordance with the requirements of the regulatory
      framework of Ukraine. Critical stages of formulation which can affect the quality
      of the finished preparation were considered during the research. The obtained
      results indicated that the quality of the finished preparation met the
      requirements of the State Pharmacopoeia of Ukraine.

PMID- 29220341
TI  - Auditing Safety of Compounding and Reconstituting of Intravenous Medicines on
      Hospital Wards in Finland.
AB  - On the hospital wards in Finland, nurses generally reconstitute intravenous
      medicines, such as antibiotics, analgesics, and antiemetics prescribed by
      doctors. Medicine reconstitution is prone to many errors. Therefore, it is
      important to identify incorrect practices in the reconstitution of medicine to
      improve patient safety in hospitals. The aim of this study was to audit the
      compounding and reconstituting of intravenous medicines on hospital wards in a
      secondary-care hospital in Finland by using an assessment tool and
      microbiological testing for identifying issues posing patient safety risks. A
      hospital pharmacist conducted an external audit by using a validated 65-item
      assessment tool for safe-medicine compounding practices on 20 wards of the
      selected hospital. Also, three different microbiological samples were collected
      to assure the aseptics. Practices were evaluated using a four-point rating scale
      of "never performed," "rarely performed," "often performed," and "always
      performed," and were based on observation and interviews with nurses or ward
      pharmacists. In addition, glove-, settle plate-, and media fill-tests were
      collected. Associations between microbial sample results and audit-tool results
      were discussed. Altogether, only six out of the 65 items were fully implemented
      in all wards; these were related to logistic practices and quality assurance.
      More than half of the wards used incorrect practices ("rarely performed" or
      "never performed") for five items. Most of these obviated practices related to
      aseptic practices. All media-fill tests were clean but the number of colony
      forming units in glove samples and settle- plate samples varied from 0 to >100.
      More contamination was found in wards where environmental conditions were
      inadequate or the use of gloves was incorrect. Compounding practices were
      [mostly] quite well adapted, but the aseptic practices needed improvement.
      Attention should have been directed particularly to good aseptic techniques and
      compounding environment on the wards. These results can be used for updating the
      guidelines and for training nurses involved in compounding.

PMID- 29220342
TI  - Effect of Penetration Enhancers on the Percuaneous Delivery of Hormone
      Replacement Actives.
AB  - Transdermal compositions for hormone replacement are comprised of exogenous
      hormones that are biochemically similar to those produced endogenously by the
      ovaries or elsewhere in the body. In this work, estradiol, estriol, and
      testosterone were loaded in transdermal vehicles, prepared using one of three
      selected penetration enhancer mixtures: Vehicle 1 (olive oil and oleic acid),
      Vehicle 2 (isopropyl palmitate and lecithin), and Vehicle 3 (isopropyl myristate
      and lecithin). The influence of penetration enhancers on transdermal delivery was
      evaluated using Franz-type diffusion cells and Normal Human 3D Model of Epidermal
      Tissue. Results showed that drug delivery is affected by the penetration enhancer
      used in the transdermal composition.

PMID- 29220343
TI  - Two techniques to sample non-volatiles in breath-exemplified by methadone.
AB  - The particles in exhaled breath provide a promising matrix for the monitoring of
      pathological processes in the airways, and also allow exposure to exogenous
      compounds to be to assessed. The collection is easy to perform and is non
      invasive. The aim of the present study is to assess if an exogenous compound
      methadone-is distributed in the lining fluid of small airways, and to compare two
      methods for collecting methadone in particles in exhaled breath. Exhaled
      particles were collected from 13 subjects receiving methadone maintenance
      treatment. Two different sampling methods were applied: one based on electret
      filtration, potentially collecting exhaled particles of all sizes, and one based
      on impaction, collecting particles in the size range of 0.5-7 MUm, known to
      reflect the respiratory tract lining fluid from the small airways. The collected
      samples were analyzed by liquid chromatography mass spectrometry, and the impact
      of different breathing patterns was also investigated. The potential contribution
      from the oral cavity was investigated by rinsing the mouth with a codeine
      solution, followed by codeine analysis of the collected exhaled particles by both
      sampling methods. The results showed that methadone was present in all samples
      using both methods, but when using the method based on impaction, the
      concentration of methadone in exhaled breath was less than 1% of the
      concentration collected by the method based on filtration. Optimizing the
      breathing pattern to retrieve particles from small airways did not increase the
      amount of exhaled methadone collected by the filtration method. The contamination
      from codeine present in the oral cavity was only detected in samples collected by
      the impaction method. We conclude that methadone is distributed in the
      respiratory tract lining fluid of small airways. The samples collected by the
      filtration method most likely contained a contribution from the upper
      airways/oral fluid in contrast to the impaction method.

PMID- 29220345
TI  - A randomized trial of bifurcation stenting technique in chronic total occlusions
      percutaneous coronary intervention.
AB  - BACKGROUND: The optimal strategy to treat bifurcation lesions (BFLs) in a
      percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs)
      remains unknown. AIMS: We sought to assess whether T-provisional or mini-crush is
      appropriate for BFLs within CTO vessels. PATIENTS AND METHODS: From January 2011
      to December 2013, patients who underwent successful CTO guidewire crossing and
      with a BFL within the CTO target vessel were enrolled prospectively and assigned
      randomly to either T-provisional stenting or the mini-crush technique for BFL
      treatment. One-year clinical follow-up was performed. Major adverse cardiac and
      cerebrovascular events (MACCE) were defined as the composite of cardiovascular
      death, myocardial infarction, target vessel revascularization, and stroke.
      RESULTS: The prevalence of BFLs was 54.3%. A total of 146 patients with BFLs
      within CTO vessel were enrolled prospectively and assigned randomly to either T
      provisional stenting (N=73) or the mini-crush technique (N=73). Angiographic and
      clinical success rates were similar in the two groups: 91.8 versus 97.2% (P=0.27)
      and 91.8 versus 94.5% (P=0.67), respectively.Although T-provisional stenting was
      associated with a nonsignificantly lower incidence of MACCE in case of BFLs
      located far from the CTO (9.3 vs. 22.2%; P=0.426), the mini-crush technique
      resulted in higher MACCE-free survival at 1 year in the presence of BFLs within
      the CTO body or close to the proximal or the distal cap (89.1 vs. 64.9%;
      P=0.007). CONCLUSION: The mini-crush technique appeared to be associated with
      improved 1-year clinical and angiographic outcomes, particularly when used to
      treat BFLs located within the CTO body or close to the proximal or the distal
      cap.

PMID- 29220346
TI  - Decreased Lymphocyte-to-Monocyte Ratio Predicts Poor Prognosis of Acute Ischemic
      Stroke Treated with Thrombolysis.
AB  - BACKGROUND Our previous study found that lower lymphocyte-to-monocyte ratio (LMR)
      is an independent risk factor of clinical outcome of acute ischemic stroke (AIS).
      However, whether lower LMR is independently associated with adverse prognosis of
      AIS treated with thrombolysis has not been determined. In this study, we explored
      the relationship between LMR and prognosis of AIS treated with thrombolysis.
      MATERIAL AND METHODS We retrospectively enrolled 108 patients treated with
      thrombolysis. LMR was calculated according to lymphocyte count and monocyte count
      on admission. Patients were classified into 3 groups according to LMR values on
      admission (group 1 LMR >4.34, group 2 LMR 2.79 to 4.34, group 3 LMR <2.79).
      Neurologic impairment was estimated by use of the National Institute of Health
      Stroke Scale. Clinical prognosis at 3 months was assessed by modified Rankin
      Scale. The relationship between LMR and neurologic impairment was analyzed by
      Spearman rank correlation. Receiver operating characteristic curve (ROC) was used
      to evaluate the ability of LMR to predict outcome. RESULTS Patients in group 3
      had lower lymphocyte counts and LMR values and higher monocyte counts (P<0.001).
      LMR value was negatively correlated with the degree of neurologic impairment (r=
      0.372, P<0.001). The ROC suggested a moderate sensitivity (71.6%) and specificity
      (80.5%) of LMR for predicting prognosis with an optimal cut-off point at 3.48.
      Higher LMR value was an independent protective factor against adverse prognosis
      (odds ratio 0.683, 95% confidence interval 0.490-0.952, P=0.024). CONCLUSIONS A
      lower LMR value is an independent predictor of poor prognosis of AIS treated with
      thrombolytic therapy.

PMID- 29220347
TI  - Assessing the benefits of five years of different approaches to treatment of
      urogenital schistosomiasis: A SCORE project in Northern Mozambique.
AB  - BACKGROUND: In Mozambique, schistosomiasis is highly endemic across the whole
      country. The Schistosomiasis Consortium for Operational Research and Evaluation
      (SCORE) coordinates a five-year study that has been implemented in various
      African countries, including Mozambique. The overall goal of SCORE was to better
      understand how to best apply preventive chemotherapy with praziquantel (PZQ) for
      schistosomiasis control by evaluating the impact of alternative treatment
      approaches. METHODS: This was a cluster-randomised trial that compared the impact
      of different treatment strategies in study areas with prevalence among school
      children of >=21% S. haematobium infection by urine dipstick. Each village was
      randomly allocated to one of six possible combinations of community-wide
      treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period
      of four years, followed by final data collection in the fifth year. The most
      intense intervention arm involved four years of CWT, while the least intensive
      arm involved two years of SBT followed by two consecutive years of PZQ holiday.
      Each study arm included 25 villages randomly assigned to one of the six treatment
      arms. The primary outcome of interest was change in prevalence and intensity of
      S. haematobium among 100 children aged 9-to-12-years that were sampled each year
      in every village. In addition to children aged 9-to-12 years, 100 children aged 5
      8 years in their first-year of school and 50 adults (aged 20-55 years) were
      tested in the first and final fifth year of the study. Prevalence and intensity
      of S. haematobium infection was evaluated by two filtrations, each of 10mL, from
      a single urine specimen. PRINCIPAL FINDINGS: In total, data was collected from
      81,167 individuals across 149 villages in ten districts of Cabo Delgado province,
      Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in
      the prevalence of S. haematobium infection from Year 1 to Year 5, where the
      average prevalence went from 60.5% to 38.8%, across all age groups and treatment
      arms. The proportion of those heavily infected also reduced from 17.6% to 11.9%
      over five years. There was a significantly higher likelihood of males being
      infected than females at baseline, but no significant difference between the
      sexes in their response to treatment. The only significant response based on a
      study arm was seen in both the 9-to-12-year-old and first-year cross sections,
      where two consecutive treatment holidays resulted in a significantly higher final
      prevalence of S. haematobium than no treatment holidays. When the arms were
      grouped together, four rounds of treatment (regardless of whether it was CWT or
      SBT), however, did result in a significantly greater reduction in S. haematobium
      prevalence than two rounds of treatment (i.e. with two intermittent or
      consecutive holiday years) over a five-year period. CONCLUSIONS: Although PC was
      successful in reducing the burden of active infection, even among those heavily
      infected, annual CWT did not have a significantly greater impact on disease
      prevalence or intensity than less intense treatment arms. This may be due to
      extremely high starting prevalence and intensity in the study area, with frequent
      exposure to reinfection, or related to challenges in achieving high treatment
      coverage More frequent treatment had a greater impact on prevalence and intensity
      of infection when arms were grouped by number of treatments, however, cost
      efficiency was greater in arms only receiving two treatments. Finally, a
      significant reduction in prevalence of S. haematobium was seen in adults even in
      the SBT arms implying the rate of transmission in the community had been
      decreased, even where only school children have been treated, which has
      significant logistical and cost-saving implications for a national control
      programme in justifying CWT.

PMID- 29220348
TI  - The pea branching RMS2 gene encodes the PsAFB4/5 auxin receptor and is involved
      in an auxin-strigolactone regulation loop.
AB  - Strigolactones (SLs) are well known for their role in repressing shoot branching.
      In pea, increased transcript levels of SL biosynthesis genes are observed in
      stems of highly branched SL deficient (ramosus1 (rms1) and rms5) and SL response
      (rms3 and rms4) mutants indicative of negative feedback control. In contrast, the
      highly branched rms2 mutant has reduced transcript levels of SL biosynthesis
      genes. Grafting studies and hormone quantification led to a model where RMS2
      mediates a shoot-to-root feedback signal that regulates both SL biosynthesis gene
      transcript levels and xylem sap levels of cytokinin exported from roots. Here we
      cloned RMS2 using synteny with Medicago truncatula and demonstrated that it
      encodes a putative auxin receptor of the AFB4/5 clade. Phenotypes similar to rms2
      were found in Arabidopsis afb4/5 mutants, including increased shoot branching,
      low expression of SL biosynthesis genes and high auxin levels in stems. Moreover,
      afb4/5 and rms2 display a specific resistance to the herbicide picloram. Yeast
      two-hybrid experiments supported the hypothesis that the RMS2 protein functions
      as an auxin receptor. SL root feeding using hydroponics repressed auxin levels in
      stems and down-regulated transcript levels of auxin biosynthesis genes within one
      hour. This auxin down-regulation was also observed in plants treated with the
      polar auxin transport inhibitor NPA. Together these data suggest a homeostatic
      feedback loop in which auxin up-regulates SL synthesis in an RMS2-dependent
      manner and SL down-regulates auxin synthesis in an RMS3 and RMS4-dependent
      manner.

PMID- 29220351
TI  - Driver fatigue detection through multiple entropy fusion analysis in an EEG-based
      system.
AB  - Driver fatigue is an important contributor to road accidents, and fatigue
      detection has major implications for transportation safety. The aim of this
      research is to analyze the multiple entropy fusion method and evaluate several
      channel regions to effectively detect a driver's fatigue state based on
      electroencephalogram (EEG) records. First, we fused multiple entropies, i.e.,
      spectral entropy, approximate entropy, sample entropy and fuzzy entropy, as
      features compared with autoregressive (AR) modeling by four classifiers. Second,
      we captured four significant channel regions according to weight-based electrodes
      via a simplified channel selection method. Finally, the evaluation model for
      detecting driver fatigue was established with four classifiers based on the EEG
      data from four channel regions. Twelve healthy subjects performed continuous
      simulated driving for 1-2 hours with EEG monitoring on a static simulator. The
      leave-one-out cross-validation approach obtained an accuracy of 98.3%, a
      sensitivity of 98.3% and a specificity of 98.2%. The experimental results
      verified the effectiveness of the proposed method, indicating that the multiple
      entropy fusion features are significant factors for inferring the fatigue state
      of a driver.

PMID- 29220349
TI  - Neural correlates of motor-cognitive dual-tasking in young and old adults.
AB  - When two tasks are performed simultaneously, performance often declines in one or
      both tasks. These so-called dual-task costs are more pronounced in old than in
      young adults. One proposed neurological mechanism of the dual-task costs is that
      old compared with young adults tend to execute single-tasks with higher brain
      activation. In the brain regions that are needed for both tasks, the reduced
      residual capacity may interfere with performance of the dual-task. This
      competition for shared brain regions has been called structural interference. The
      purpose of the study was to determine whether structural interference indeed
      plays a role in the age-related decrease in dual-task performance. Functional
      magnetic resonance imaging (fMRI) was used to investigate 23 young adults (20-29
      years) and 32 old adults (66-89 years) performing a calculation (serial
      subtraction by seven) and balance-simulation (plantar flexion force control) task
      separately or simultaneously. Behavioral performance decreased during the dual
      task compared with the single-tasks in both age groups, with greater dual-task
      costs in old compared with young adults. Brain activation was significantly
      higher in old than young adults during all conditions. Region of interest
      analyses were performed on brain regions that were active in both tasks.
      Structural interference was apparent in the right insula, as quantified by an age
      related reduction in upregulation of brain activity from single- to dual-task.
      However, the magnitude of upregulation did not correlate with dual-task costs.
      Therefore, we conclude that the greater dual-task costs in old adults were
      probably not due to increased structural interference.

PMID- 29220350
TI  - Deep sequencing of near full-length HIV-1 genomes from plasma identifies
      circulating subtype C and infrequent occurrence of AC recombinant form in
      Southern India.
AB  - India has the third largest number of HIV-1-infected individuals accounting for
      approximately 2.1 million people, with a predominance of circulating subtype C
      strains and a low prevalence of subtype A and A1C and BC recombinant forms,
      identified over the past two decades. Recovery of near full-length HIV-1 genomes
      from a plasma source coupled with advances in next generation sequencing (NGS)
      technologies and development of universal methods for amplifying whole genomes of
      HIV-1 circulating in a target geography or population provides the opportunity
      for a detailed analysis of HIV-1 strain identification, evolution and dynamics.
      Here we describe the development and implementation of approaches for HIV-1 NGS
      analysis in a southern Indian cohort. Plasma samples (n = 20) were obtained from
      HIV-1-confirmed individuals living in and around the city of Bengaluru. Near full
      length genome recovery was obtained for 9 Indian HIV-1 patients, with recovery of
      full-length gag and env genes for 10 and 2 additional subjects, respectively.
      Phylogenetic analyses indicate the majority of sequences to be represented by
      subtype C viruses branching within a monophyletic clade, comprising viruses from
      India, Nepal, Myanmar and China and closely related to a southern African
      cluster, with a low prevalence of the A1C recombinant form also present.
      Development of algorithms for bespoke recovery and analysis at a local level will
      further aid clinical management of HIV-1 infected Indian subjects and delineate
      the progress of the HIV-1 pandemic in this and other geographical regions.

PMID- 29220352
TI  - How do slums change the relationship between urbanization and the carbon
      intensity of well-being?
AB  - This study examines how the relationship between urbanization (measured as the
      percentage of total population living in urban areas) and the carbon intensity of
      well-being (CIWB) (measured as a ratio of carbon dioxide emissions and life
      expectancy) in most nations from 1960-2013 varies based on the economic context
      and whereabouts of a substantial portion of a nation's urban population. To
      accomplish this, we use the United Nations' (UN) definition of slum households to
      identify developing countries that have substantial slum populations, and
      estimate a Prais-Winsten regression model with panel-corrected standard errors
      (PCSE), allowing for disturbances that are heteroskedastic and contemporaneously
      correlated across panels. Our findings indicate that the rate of increase in CIWB
      for countries without substantial slum populations begins to slow down at higher
      levels of urbanization, however, the association between urbanization and CIWB is
      much smaller in countries with substantial slum populations. Overall, while
      urbanization is associated with increases in CIWB, the relationship between urban
      development and CIWB is vastly different in developed nations without slums than
      in under-developed nations with slums.

PMID- 29220353
TI  - Research on HIV cure: Mapping the ethics landscape.
AB  - In an essay, Karine Dube and coauthors discuss the ethics of preclinical and
      clinical studies relevant to achieving an HIV cure.

PMID- 29220355
TI  - Adults with patellofemoral pain do not exhibit manifestations of peripheral and
      central sensitization when compared to healthy pain-free age and sex matched
      controls - An assessor blinded cross-sectional study.
AB  - Patellofemoral Pain (PFP) is highly prevalent among adults and adolescents.
      Localized mechanical hyperalgesia around the knee and tibialis anterior have been
      observed in people with PFP, but limited knowledge of potential manifestations of
      central sensitisation exists. The aims of this study were to study conditioned
      pain modulation (CPM) and wide-spread hyperalgesia in adults with PFP. This
      assessor-blinded cross-sectional study design compared CPM and mechanical
      pressure pain thresholds (PPT) between 33 adults (23 females) diagnosed with PFP
      and 32 age and sex matched pain-free controls. The investigator taking the PPT
      measurements was blinded to which participants had PFP. PPTs were reliably
      measured using a Somedic hand-held pressure algometer at three sites: 1) The
      centre of the patella, 2) the tibialis anterior muscle and 3) a remote site on
      the lateral epicondyle. For the assessment of CPM, experimental pain was induced
      to the contralateral hand by immersion into a cold water bath (conditioning
      stimulus), and assessment of PPTs (the test stimulus) was performed before and
      immediately after the conditioning stimulation. On average, the CPM paradigm
      induced a significant increase in PPTs across the three sites (6.3-13.5%,
      P<0.05), however there was no difference in CPM between young adults with PFP
      compared to the control group, (F(1,189) = 0.39, P = 0.89). There was no
      difference in mechanical PPTs between the two groups (F(1,189) = 0.03, P = 0.86).
      Contrary to our a-priori hypothesis, we found no difference in CPM or PPT between
      young adults with PFP and age and sex matched pain-free controls.

PMID- 29220354
TI  - Interpreting ambiguous 'trace' results in Schistosoma mansoni CCA Tests:
      Estimating sensitivity and specificity of ambiguous results with no gold
      standard.
AB  - BACKGROUND: The development of new diagnostics is an important tool in the fight
      against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity
      and specificity of tests in the absence of a gold standard. The main field
      diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very
      sensitive at low infection intensities. A point-of-care circulating cathodic
      antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can
      return an ambiguous 'trace' result between 'positive' and 'negative', and much
      debate has focused on interpretation of traces results. METHODOLOGY/PRINCIPLE
      FINDINGS: We show how LCA can be extended to include ambiguous trace results and
      analyse S. mansoni studies from both Cote d'Ivoire (CdI) and Uganda. We compare
      the diagnostic performance of KK and CCA and the observed results by each test to
      the estimated infection prevalence in the population. Prevalence by KK was higher
      in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between
      countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and
      9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The
      estimated sensitivity of CCA was more consistent between countries than the
      estimated sensitivity of KK, and estimated infection prevalence did not
      significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by
      CCA with trace as positive did not differ significantly from estimates of
      infection prevalence in either country, whereas both KK and CCA with trace as
      negative significantly underestimated infection prevalence in both countries.
      CONCLUSIONS: Incorporation of ambiguous results into an LCA enables the effect of
      different treatment thresholds to be directly assessed and is applicable in many
      fields. Our results showed that CCA with trace as positive most accurately
      estimated infection prevalence.

PMID- 29220356
TI  - Color Doppler ultrasonography as an alternative tool for postoperative evaluation
      of collaterals after indirect revascularization surgery in Moyamoya disease.
AB  - The cerebral hypoperfusion caused by chronic progressive stenosis or occlusion of
      intracranial arteries in moyamoya disease can be treated by direct bypass or
      indirect revascularization procedures. The extent of collaterals from the
      external carotid artery (ECA) after indirect revascularization surgery is the key
      point of angiographic follow-up, and the invasiveness of angiography impelled us
      to investigate the role of ultrasonography in the evaluation of collaterals. We
      hypothesized that the collaterals shown on angiography might produce
      corresponding hemodynamic changes in color Doppler ultrasonography. We
      prospectively recruited moyamoya patients who underwent indirect
      revascularization surgery and received both preoperative and postoperative
      angiography and color Doppler ultrasound studies. The collaterals on angiography
      were graded according to Matsushima method. A total of 21 patients (age, 17 +/-
      10.2 years) with 24 operated hemispheres were enrolled. Patients who showed
      better collateral establishment by angiography had higher end-diastolic velocity
      (EDV), lower resistance index (RI), and larger flow volume in the superficial
      temporal artery (STA) and ECA (all p < 0.05). In STA, increase of EDV greater
      than 13.5 cm/sec or reduction of RI greater than 0.19 after operation
      corresponded to 94% of Matsushima grade A+B. In ECA, post-operative EDV greater
      than 22 cm/sec or increase of EDV greater than 6.4 cm/sec also corresponded to
      94% of Matsushima grade A+B. Our findings revealed potential roles of color
      Doppler ultrasonography in identifying patients with poor collaterals after
      indirect revascularization procedures.

PMID- 29220357
TI  - Difference of the progression of pulmonary cysts assessed by computed tomography
      among COPD, lymphangioleiomyomatosis, and Birt-Hogg-Dube syndrome.
AB  - Many groups developed the methods to quantitatively analyze low attenuation area
      (LAA) on chest CT in patients with cystic lung diseases. Especially in COPD, it
      was reported that the cumulative size distribution of LAA clusters follows a
      power law characterized by the exponent D, which reflect the fractal dimension of
      terminal airspace geometry. We hypoyhesized that the quantitative charateristics
      of LAA clusters including fractal property might indicate the different features
      of the progression of cysts in cystic lung diseases. The aim of this study was to
      apply the CT image-based method of characterizing the size distribution of LAA
      clusters for lymphangioleiomyomatosis (LAM) and Birt-Hogg-Dube syndrome (BHDS) to
      disclose their features of the progression of pulmonary cysts. 40 patients with
      COPD, 52 patients with LAM, and 18 patients with BHDS who had undergone CT scans
      at our institute between January 2002 and August 2009 were included. Differences
      among these diseases in the quantitative characteristics of LAA clusters {i.e.,
      extent, number, size, fractal property, and the relationship between these
      quantitatives} were assessed. The Chi-sqsuare test, unpaired t-test, and one-way
      analyses of variance with Tukey post-hoc tests were used to compare groups,
      spline model with an interaction terms were used to assess the relationship
      between extent and number, and exponential regression model was used to assess
      the relationship between extent and size. Statistically significant differences
      separated the three diseases in extent and number (P < 0.001). Number was
      significantly correlated with extent in COPD (P < 0.001), but was not so in LAM
      and BHDS when extent exceeded 11.5% and 20.8%, respectively. Size was
      significantly correlated with extent in COPD and LAM (P < 0.001), but was not so
      in BHDS. The percentage of CT images with fractal property was higher in COPD
      than that in LAM and BHDS (95.8%, 92.9% and 63.0%, respectively). In conclusion,
      our study has demonstrated for the first time the different characteristics of
      the size distribution of LAA clusters among COPD, LAM and BHDS, and indicated
      that this method is useful for exploration of the pathophysiology in cystic lung
      diseases.

PMID- 29220358
TI  - Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after
      intranasal vaccination in rhesus macaques.
AB  - Studies in nonhuman primates (NHP) for prospective immune cell monitoring
      subsequent to infection and/or vaccination usually rely on periodic sampling of
      the blood samples with only occasional collections of biopsies from mucosal
      tissues because of safety concerns and practical constraints. Here we present
      evidence in support of cytobrush sampling of oral, rectal, and genital mucosal
      tissues as a minimally invasive approach for the phenotypic analyses of different
      T cells subsets de novo as well as prospectively after intranasal immunization in
      rhesus macaques. Significant percentages of viable lymphocytes were obtained
      consistently from both naive and chronically SIV-infected rhesus macaques. The
      percentages of CD3+ T cells in the blood were significantly higher compared to
      those in the mucosal tissues analyzed in the naive animals, while in the SIV+
      animals the CD3+ T cells were significantly elevated in the rectal tissues,
      relative to all other sites analyzed. In the naive, but not SIV+ macaques, the
      rectal and vaginal mucosal tissues, compared to oral mucosa and blood, showed
      higher diversity and percentages of CD4+ T cells expressing the HIV entry co
      receptor CCR5 and mucosal specific adhesion (CD103) as well as activation (HLA
      DR) and proliferation (Ki67) markers. Sequential daily cytobrush sampling from
      the oral, rectal, and genital mucosal tissues was performed in SIV+ animals from
      an ongoing study where they were administered intranasal immunization with
      adenoviral vectored vaccines incorporating the green fluorescent protein (GFP)
      reporter gene. We detected a transient increase in GFP+ CD4 T cells in only oral
      mucosa suggesting limited mucosal trafficking. In general, CD4+ and CD8+ T cells
      expressing Ki67 transiently increased in all mucosal tissues, but those
      expressing the CCR5, HLA-DR, and CD103 markers exhibited minor changes. We
      propose the minimally invasive cytobrush sampling as a practical approach for
      effective and prospective immune monitoring of the oral-genital mucosal tissues
      in NHP.

PMID- 29220359
TI  - Synthesis of novel purpurealidin analogs and evaluation of their effect on the
      cancer-relevant potassium channel KV10.1.
AB  - In the search for novel anticancer drugs, the potassium channel KV10.1 has
      emerged as an interesting cancer target. Here, we report a new group of KV10.1
      inhibitors, namely the purpurealidin analogs. These alkaloids are produced by the
      Verongida sponges and are known for their wide variety of bioactivities. In this
      study, we describe the synthesis and characterization of 27 purpurealidin
      analogs. Structurally, bromine substituents at the central phenyl ring and a
      methoxy group at the distal phenyl ring seem to enhance the activity on KV10.1.
      The mechanism of action of the most potent analog 5 was investigated. A shift of
      the activation curve to more negative potentials and an apparent inactivation was
      observed. Since KV10.1 inhibitors can be interesting anticancer drug lead
      compounds, the effect of 5 was evaluated on cancerous and non-cancerous cell
      lines. Compound 5 showed to be cytotoxic and appeared to induce apoptosis in all
      the evaluated cell lines.

PMID- 29220360
TI  - Substitutions of PrP N-terminal histidine residues modulate scrapie disease
      pathogenesis and incubation time in transgenic mice.
AB  - Prion diseases have been linked to impaired copper homeostasis and copper induced
      oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind
      to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites
      within the N-terminal half of the protein but information on the impact of such
      binding on conversion to the misfolded isoform often derives from studies using
      either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we
      created new transgenic mouse lines expressing PrP with disrupted copper binding
      sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G,
      H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110;
      "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel
      transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt)
      controls were susceptible to mouse-adapted scrapie strain RML but showed
      significantly prolonged incubation times. In contrast, amino acid replacement at
      residue 95 accelerated disease progression in corresponding PrP(H95G) mice.
      Neuropathological lesions in terminally ill transgenic mice were similar to
      scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition,
      however, was not synaptic as seen in wt animals, but instead dense globular
      plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc
      deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We
      conclude that OR and site 5 histidine substitutions have divergent phenotypic
      impacts and that cis interactions between the OR region and the site 5 region
      modulate pathogenic outcomes by affecting the PrP globular domain.

PMID- 29220361
TI  - Pre-stimulus pupil dilation and the preparatory control of attention.
AB  - Task preparation involves multiple component processes, including a general
      evaluative process that signals the need for adjustments in control, and the
      engagement of task-specific control settings. Here we examined the dynamics of
      these different mechanisms in preparing the attentional control system for visual
      search. We explored preparatory activity using pupil dilation, a well-established
      measure of task demands and effortful processing. In an initial exploratory
      experiment, participants were cued at the start of each trial to search for
      either a salient color singleton target (an easy search task) or a low-salience
      shape singleton target (a difficult search task). Pupil dilation was measured
      during the preparation period from cue onset to search display onset. Mean
      dilation was larger in preparation for the difficult shape target than the easy
      color target. In two additional experiments, we sought to vary effects of
      evaluative processing and task-specific preparation separately. Experiment 2
      showed that when the color and shape search tasks were matched for difficulty,
      the shape target no longer evoked larger dilations, and the pattern of results
      was in fact reversed. In Experiment 3, we manipulated difficulty within a single
      feature dimension, and found that the difficult search task evoked larger
      dilations. These results suggest that pupil dilation reflects expectations of
      difficulty in preparation for a search task, consistent with the activity of an
      evaluative mechanism. We did not find consistent evidence for relationship
      between pupil dilation and search performance (accuracy and response timing),
      suggesting that pupil dilation during search preparation may not be strongly
      linked to ongoing task-specific preparation.

PMID- 29220362
TI  - Optimized plasma preparation is essential to monitor platelet-stored molecules in
      humans.
AB  - Platelets store a plethora of different molecules within their granules,
      modulating numerous pathways, not only in coagulation, but also in angiogenesis,
      wound healing, and inflammatory diseases. These molecules get rapidly released
      upon activation and therefore represent an easily accessible indirect marker for
      platelet activation. Accurate analysis of platelet-derived molecules in the
      plasma requires appropriate anticoagulation to avoid in vitro activation and
      subsequent degranulation of platelets, potentially causing artificially high
      levels and masking biologically relevant differences within translational
      research studies. However, there is still enormous heterogeneity among
      anticoagulants used to prevent unwanted platelet activation, so that plasma
      levels reported for platelet granule contents range over several orders of
      magnitude. To address this problem and to define the most robust method of plasma
      preparation to avoid in vitro platelet activation during processing, we compared
      plasma concentrations of the three platelet-stored factors thrombospondin (TSP
      1), platelet factor 4 (PF4), and soluble P-selectin (sCD62P) between human blood
      samples anticoagulated with either citrate-theophylline-adenosine-dipyridamole
      (CTAD), acid-citrate-dextrose (ACD), citrate, ethylenediaminetetraacetic acid
      (EDTA) or heparin. Additionally, we assessed the effect of storage temperature
      and time between blood drawing and sample processing within the differentially
      anticoagulated samples. Our data strongly support the use of CTAD as
      anticoagulant for determining plasma concentrations of platelet-stored molecules,
      as anticoagulation with heparin or EDTA led to a 12.4- or 8.3-fold increase in
      plasma levels of PF4, respectively. Whereas ACD was similar effective as CTAD,
      citrate only showed comparable PF4 plasma levels when plasma was kept at 4
      degrees C. Moreover, blood sampling with CTAD as anticoagulant resulted in the
      most reproducible values, even when samples were processed at ambient temperature
      or after storage over 6 hours. In the latter case, anticoagulation with heparin
      or EDTA led to artificially high plasma levels indicative of in vitro platelet
      activation. Therefore, we want to raise scientific awareness for choosing CTAD as
      optimal anticoagulant for the detection of platelet-stored molecules in plasma.

PMID- 29220363
TI  - Self-organization in a diversity induced thermodynamics.
AB  - In this work we show how global self-organized patterns can come out of a
      disordered ensemble of point oscillators, as a result of a deterministic, and not
      of a random, cooperative process. The resulting system dynamics has many
      characteristics of classical thermodynamics. To this end, a modified Kuramoto
      model is introduced, by including Euclidean degrees of freedom and particle
      polarity. The standard deviation of the frequency distribution is the disorder
      parameter, diversity, acting as temperature, which is both a source of motion and
      of disorder. For zero and low diversity, robust static phase-synchronized
      patterns (crystals) appear, and the problem reverts to a generic dissipative many
      body problem. From small to moderate diversity crystals display vibrations
      followed by structure disintegration in a competition of smaller dynamic
      patterns, internally synchronized, each of which is capable to manage its
      internal diversity. In this process a huge variety of self-organized dynamic
      shapes is formed. Such patterns can be seen again as (more complex) oscillators,
      where the same description can be applied in turn, renormalizing the problem to a
      bigger scale, opening the possibility of pattern evolution. The interaction
      functions are kept local because our idea is to build a system able to produce
      global patterns when its constituents only interact at the bond scale. By further
      increasing the oscillator diversity, the dynamics becomes erratic, dynamic
      patterns show short lifetime, and finally disappear for high diversity. Results
      are neither qualitatively dependent on the specific choice of the interaction
      functions nor on the shape of the probability function assumed for the
      frequencies. The system shows a phase transition and a critical behaviour for a
      specific value of diversity.

PMID- 29220364
TI  - An attempt to interpret a biochemical mechanism of C4 photosynthetic thermo
      tolerance under sudden heat shock on detached leaf in elevated CO2 grown maize.
AB  - Detached leaves at top canopy structures always experience higher solar
      irradiance and leaf temperature under natural conditions. The ability of
      tolerance to high temperature represents thermotolerance potential of whole
      plants, but was less of concern. In this study, we used a heat-tolerant (B76) and
      a heat-susceptible (B106) maize inbred line to assess the possible mitigation of
      sudden heat shock (SHS) effects on photosynthesis (PN) and C4 assimilation
      pathway by elevated [CO2]. Two maize lines were grown in field-based open top
      chambers (OTCs) at ambient and elevated (+180 ppm) [CO2]. Top-expanded leaves for
      30 days after emergence were suddenly exposed to a 45 degrees C SHS for 2 hours
      in midday during measurements. Analysis on thermostability of cellular membrane
      showed there was 20% greater electrolyte leakage in response to the SHS in B106
      compared to B76, in agreement with prior studies. Elevated [CO2] protected PN
      from SHS in B76 but not B106. The responses of PN to SHS among the two lines and
      grown CO2 treatments were closely correlated with measured decreases of NADP-ME
      enzyme activity and also to its reduced transcript abundance. The SHS treatments
      induced starch depletion, the accumulation of hexoses and also disrupted the TCA
      cycle as well as the C4 assimilation pathway in the both lines. Elevated [CO2]
      reversed SHS effects on citrate and related TCA cycle metabolites in B106 but the
      effects of elevated [CO2] were small in B76. These findings suggested that heat
      stress tolerance is a complex trait, and it is difficult to identify biochemical,
      physiological or molecular markers that accurately and consistently predict heat
      stress tolerance.

PMID- 29220365
TI  - A novel methodology for strengthening human rights based monitoring in public
      health: Family planning indicators as an illustrative example.
AB  - OBJECTIVE: The last few years have seen a rise in the number of global and
      national initiatives that seek to incorporate human rights into public health
      practice. Nonetheless, a lack of clarity persists regarding the most appropriate
      indicators to monitor rights concerns in these efforts. The objective of this
      work was to develop a systematic methodology for use in determining the extent to
      which indicators commonly used in public health capture human rights concerns,
      using contraceptive services and programmes as a case study. METHODS: The
      approach used to identify, evaluate, select and review indicators for their human
      rights sensitivity built on processes undertaken in previous work led by the
      World Health Organization (WHO). With advice from an expert advisory group, an
      analytic framework was developed to identify and evaluate quantitative,
      qualitative, and policy indicators in relation to contraception for their
      sensitivity to human rights. To test the framework's validity, indicators were
      reviewed to determine their feasibility to provide human rights analysis with
      attention to specific rights principles and standards. FINDINGS: This exercise
      resulted in the identification of indicators that could be used to monitor human
      rights concerns as well as key gaps where additional indicators are required.
      While indicators generally used to monitor contraception programmes have some
      degree of sensitivity to human rights, breadth and depth are lacking. CONCLUSION:
      The proposed methodology can be useful to practitioners, researchers, and policy
      makers working in any area of health who are interested in monitoring and
      evaluating attention to human rights in commonly used health indicators.

PMID- 29220366
TI  - The distinct effects of orally administered Lactobacillus rhamnosus GG and
      Lactococcus lactis subsp. lactis C59 on gene expression in the murine small
      intestine.
AB  - The molecular mechanisms of strain-specific probiotic effects and the impact of
      the oral administration of probiotic strains on the host's gene expression are
      not yet well understood. The aim of this study was to investigate the strain
      specific effects of probiotic strain intake on gene expression in the murine
      small intestine. Two distinct strains of lactic acid bacteria, Lactobacillus
      rhamnosus GG (GG) and Lactococcus lactis subsp. lactis C59 (C59), were orally
      administered to BALB/c mice, daily for 2 weeks. The total RNA was isolated from
      the upper (including the duodenum) and lower (the terminal ileum) small
      intestine, and gene expression was assessed by microarray analysis. The data
      revealed (1) oral administration of C59 and GG markedly down-regulated the
      expression of genes encoding fibrinogen subunits and plasminogen in the upper
      small intestine; (2) administration of more than 1 * 107 CFU/day of GG changed
      the gene expression of the host ileum. (3) strain- and dose-related effects on
      various GO biological processes; and (4) enrichment for B cell-related Gene
      Ontology terms among up-regulated genes in the terminal ileum of mice
      administered the 1 * 109 CFU/day of GG. The distinct effects of GG and C59 on
      gene expression in the intact small intestine provide clues to understand how the
      health beneficial effects of specific strains of probiotic bacteria are mediated
      by interactions with intestinal cells.

PMID- 29220367
TI  - Periodontitis is associated with significant hepatic fibrosis in patients with
      non-alcoholic fatty liver disease.
AB  - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) has a
      bidirectional association with metabolic syndrome. It affects up to 30% of the
      general population, 70% of individuals with diabetes and 90% with obesity. The
      main histological hallmark of progressive NAFLD is fibrosis. There is a
      bidirectional epidemiological link between periodontitis and metabolic syndrome.
      NAFLD, periodontitis and diabetes share common risk factors, are characterised by
      inflammation and associated with changes in commensal bacteria. Therefore we
      tested the hypothesis that periodontitis is associated with NAFLD and with
      significant fibrosis in two study groups. METHODS: We analyzed data from a
      population-based survey and a patient-based study. NHANES III participants with
      abdominal ultrasound and sociodemographic, clinical, and oral examination data
      were extracted and appropriate weighting applied. In a separate patient-based
      study, consenting patients with biopsy-proved NAFLD (or with liver indices too
      mild to justify biopsy) underwent dental examination. Basic Periodontal
      Examination score was recorded. RESULTS: In NHANES, periodontitis was
      significantly associated with steatosis in 8172 adults even after adjusting for
      sociodemographic factors. However, associations were fully explained after
      accounting for features of metabolic syndrome. In the patient-based study,
      periodontitis was significantly more common in patients with biopsy-proven NASH
      and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more
      common in patients with NASH and significant fibrosis (F2-4) than mild or no
      fibrosis (F0-1, p = 0.04). CONCLUSIONS: Complementary evidence from an
      epidemiological survey and a clinical study show that NAFLD is associated with
      periodontitis and that the association is stronger with significant liver
      fibrosis.

PMID- 29220368
TI  - Increased sediment load during a large-scale dam removal changes nearshore
      subtidal communities.
AB  - The coastal marine ecosystem near the Elwha River was altered by a massive
      sediment influx-over 10 million tonnes-during the staged three-year removal of
      two hydropower dams. We used time series of bathymetry, substrate grain size,
      remotely sensed turbidity, scuba dive surveys, and towed video observations
      collected before and during dam removal to assess responses of the nearshore
      subtidal community (3 m to 17 m depth). Biological changes were primarily driven
      by sediment deposition and elevated suspended sediment concentrations.
      Macroalgae, predominantly kelp and foliose red algae, were abundant before dam
      removal with combined cover levels greater than 50%. Where persistent sediment
      deposits formed, macroalgae decreased greatly or were eliminated. In areas
      lacking deposition, macroalgae cover decreased inversely to suspended sediment
      concentration, suggesting impacts from light reduction or scour. Densities of
      most invertebrate and fish taxa decreased in areas with persistent sediment
      deposition; however, bivalve densities increased where mud deposited over sand,
      and flatfish and Pacific sand lance densities increased where sand deposited over
      gravel. In areas without sediment deposition, most invertebrate and fish taxa
      were unaffected by increased suspended sediment or the loss of algae cover
      associated with it; however, densities of tubeworms and flatfish, and primary
      cover of sessile invertebrates increased suggesting benefits of increased
      particulate matter or relaxed competition with macroalgae for space. As dam
      removal neared completion, we saw evidence of macroalgal recovery that likely
      owed to water column clearing, indicating that long-term recovery from dam
      removal effects may be starting. Our results are relevant to future dam removal
      projects in coastal areas and more generally to understanding effects of
      increased sedimentation on nearshore subtidal benthic communities.

PMID- 29220369
TI  - Can mother-to-child transmission of HIV be eliminated without addressing the
      issue of stigma? Modeling the case for a setting in South Africa.
AB  - BACKGROUND: Stigma and discrimination ontinue to undermine the effectiveness of
      the HIV response. Despite a growing body of evidence of the negative relationship
      between stigma and HIV outcomes, there is a paucity of data available on the
      prevalence of stigma and its impact. We present a probabilistic cascade model to
      estimate the magnitude of impact stigma has on mother-to-child-transmission
      (MTCT). METHODS: The model was parameterized using 2010 data from Johannesburg,
      South Africa, from which loss-to-care at each stage of the antenatal cascade were
      available. Three scenarios were compared to assess the individual contributions
      of stigma, non-stigma related barriers, and drug ineffectiveness on the overall
      number of infant infections. Uncertainty analysis was used to estimate plausible
      ranges. The model follows the guidelines in place in 2010 when the data were
      extracted (WHO Option A), and compares this with model results had Option B+ been
      implemented at the time. RESULTS: The model estimated under Option A, 35% of
      infant infections being attributed to stigma. This compares to 51% of total
      infections had Option B+ been implemented in 2010. Under Option B+, the model
      estimated fewer infections than Option A, due to the availability of more
      effective drugs. Only 8% (Option A) and 9% (Option B+) of infant infections were
      attributed to drug ineffectiveness, with the trade-off in the proportion of
      infections being between stigma and non-stigma-related barriers. CONCLUSIONS: The
      model demonstrates that while the effect of stigma on retention of women at any
      given stage along the cascade can be relatively small, the cumulative effect can
      be large. Reducing stigma may be critical in reaching MTCT elimination targets,
      because as countries improve supply-side factors, the relative impact of stigma
      becomes greater. The cumulative nature of the PMTCT cascade results in stigma
      having a large effect, this feature may be harnessed for efficiency in investment
      by prioritizing interventions that can affect multiple stages of the cascade
      simultaneously.

PMID- 29220370
TI  - Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy
      cases.
AB  - BACKGROUND: A recent publication suggested molecular mimicry of a nucleoprotein
      (NP) sequence from A/Puerto Rico/8/1934 (PR8) strain, the backbone used in the
      construction of the reassortant strain X-179A that was used in Pandemrix(r)
      vaccine, and reported on anti-hypocretin (HCRT) receptor 2 (anti-HCRTR2)
      autoantibodies in narcolepsy, mostly in post Pandemrix(r) narcolepsy cases (17 of
      20 sera). In this study, we re-examined this hypothesis through mass spectrometry
      (MS) characterization of Pandemrix(r), and two other pandemic H1N1 (pH1N1)-2009
      vaccines, Arepanrix(r) and Focetria(r), and analyzed anti-HCRTR2 autoantibodies
      in narcolepsy patients and controls using three independent strategies. METHODS:
      MS characterization of Pandemrix(r) (2 batches), Arepanrix(r) (4 batches) and
      Focetria(r) (1 batch) was conducted with mapping of NP 116I or 116M spectrogram.
      Two sets of narcolepsy cases and controls were used: 40 post Pandemrix(r)
      narcolepsy (PP-N) cases and 18 age-matched post Pandemrix(r) controls (PP-C), and
      48 recent (<=6 months) early onset narcolepsy (EO-N) cases and 70 age-matched
      other controls (O-C). Anti-HCRTR2 autoantibodies were detected using three
      strategies: (1) Human embryonic kidney (HEK) 293T cells with transient expression
      of HCRTR2 were stained with human sera and then analyzed by flow cytometer; (2)
      In vitro translation of [35S]-radiolabelled HCRTR2 was incubated with human sera
      and immune complexes of autoantibody and [35S]-radiolabelled HCRTR2 were
      quantified using a radioligand-binding assay; (3) Optical density (OD) at 450 nm
      (OD450) of human serum immunoglobulin G (IgG) binding to HCRTR2 stably expressed
      in Chinese hamster ovary (CHO)-K1 cell line was measured using an in-cell enzyme
      linked immunosorbent assay (ELISA). RESULTS: NP 116M mutations were predominantly
      present in all batches of Pandemrix(r), Arepanrix(r) and Focetria(r). The wild
      type NP109-123 (ILYDKEEIRRIWRQA), a mimic to HCRTR234-45 (YDDEEFLRYLWR), was not
      found to bind to DQ0602. Three or four subjects were found positive for anti
      HCRTR2 autoantibodies using two strategies or the third one, respectively. None
      of the post Pandemrix(r) narcolepsy cases (0 of 40 sera) was found positive with
      all three strategies. CONCLUSION: Anti-HCRTR2 autoantibody is not a significant
      biological feature of narcolepsy or of post Pandemrix(r) autoimmune responses.

PMID- 29220371
TI  - The impact of different anti-vascular endothelial growth factor treatment
      regimens on reducing burden for caregivers and patients with wet age-related
      macular degeneration in a single-center real-world Japanese setting.
AB  - OBJECTIVE: To describe the burden associated with different anti-vascular
      endothelial growth factor (VEGF) treatment strategies for wet age-related macular
      degeneration (wAMD) in a real-word setting in Japan. METHODS: Single-center,
      cross-sectional survey of caregivers of patients with wAMD performed in a
      hospital in Mito-City, a rural area in Japan. Caregiver burden was evaluated
      using the Burden Index of Caregivers (BIC-11), and depressive symptoms were
      assessed by the Center for Epidemiologic Studies Depression scale. Retrospective
      medical chart review was conducted to monitor resource use and visual acuity
      outcomes in patients. The productivity loss of caregivers accompanying patients
      on hospital visits was estimated using the human capital method. RESULTS: Seventy
      one patient-caregiver pairs were included. Most caregivers were female (74.6%),
      spouse/partner (54.9%), employed (46.5%), and the primary caregiver (85.9%).
      Patients received anti-VEGF treatment as follows: treat-and-extend (T&E; n = 42),
      switch (from as-needed [PRN] to T&E; n = 18), PRN (n = 10), and other (n = 1).
      Caregiver-related burden (total BIC-11 scores) were 4.29 (T&E) 4.60 (PRN), and
      5.33 (switch) (p = NS). The mean number of hospital visits was lower with T&E
      than PRN (7.88 vs. 14.0 [p = 0.00674] in year 1 and 5.68 vs. 9.0 in year 2). For
      patients who switched from PRN to T&E, the mean number of hospital visits
      decreased from 13.21 to 7.43 (p<0.0001) in the first year after switch. The
      productivity loss associated with accompanying patients to the hospital was lower
      for caregivers of patients receiving T&E than PRN (mean differences: 74,456.04
      JPY [p = 0.00284] in year 1 and 40843.14 JPY in year 2), and was also reduced for
      caregivers of patients who switched from PRN to T&E. CONCLUSION: wAMD treatment
      with anti-VEGF agents via T&E reduced hospital visits compared with PRN, where
      associated monitoring visits are necessary to provide good patient outcomes. T&E
      was associated with a reduction trend in caregiver burden, including time and
      costs.

PMID- 29220372
TI  - The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding
      to the histone-like HU protein.
AB  - DNA mimicry is a direct and effective strategy by which the mimic competes with
      DNA for the DNA binding sites on other proteins. Until now, only about a dozen
      proteins have been shown to function via this strategy, including the DNA mimic
      protein DMP19 from Neisseria meningitides. We have shown previously that DMP19
      dimer prevents the operator DNA from binding to the transcription factor NHTF.
      Here, we provide new evidence that DMP19 monomer can also interact with the
      Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration
      and isothermal titration calorimetry assays, we found that DMP19 uses its
      monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated
      mass spectrometry was used to investigate the binding mode of DMP19 monomer and
      HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that
      the DNA binding affinity of HU is affected by DMP19. These results showed that
      DMP19 is bifunctional in the gene regulation of Neisseria through its variable
      oligomeric forms.

PMID- 29220373
TI  - Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol
      induced cervical sympathetic ganglion block?
AB  - This study aimed to determine whether nerve regeneration by means of an
      artificial nerve conduit is promoted by ethanol-induced cervical sympathetic
      ganglion block (CSGB) in a canine model. This study involved two experiments-in
      part I, the authors examined the effect of CSGB by ethanol injection on long-term
      blood flow to the orofacial region; part II involved evaluation of the effect of
      CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using
      polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left
      CSGB by injection of 99.5% ethanol under direct visualization by means of
      thoracotomy, and changes in oral mucosal blood flow in the mental region and
      nasal skin temperature were evaluated. The increase in blood flow on the left
      side lasted for 7 weeks, while the increase in average skin temperature lasted 10
      weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles
      were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in
      the left IAN. A week after surgery, seven of these dogs were administered CSGB by
      injection of ethanol. Electrophysiological findings at 3 months after surgery
      revealed significantly higher sensory nerve conduction velocity and recovery
      index (ratio of left and right IAN peak amplitudes) after nerve regeneration in
      the reconstruction+CSGB group than in the reconstruction-only group. Myelinated
      axons in the reconstruction+CSGB group were greater in diameter than those in the
      reconstruction-only group. Administration of CSGB with ethanol resulted in
      improved nerve regeneration in some IAN defects. However, CSGB has several
      physiological effects, one of which could possibly be the long-term increase in
      adjacent blood flow.

PMID- 29220374
TI  - A blaOXA-181-harbouring multi-resistant ST147 Klebsiella pneumoniae isolate from
      Pakistan that represent an intermediate stage towards pan-drug resistance.
AB  - Carbapenem resistant Klebsiella pneumoniae (CR-KP) infections are an ever
      increasing global issue, especially in the Indian subcontinent. Here we report
      genetic insight into a blaOXA-181 harbouring Klebsiella pneumoniae, belonging to
      the pandemic lineage ST147, that represents an intermediate stage towards pan
      drug resistance. The CR-KP isolate DA48896 was isolated from a patient from
      Pakistan and was susceptible only to tigecycline and colistin. It harboured
      blaOXA-181 and was assigned to sequence type ST147. Analysis from whole genome
      sequencing revealed a very high sequence similarity to the previously sequenced
      pan-resistant K. pneumoniae isolate MS6671 from the United Arab Emirates. The two
      isolates are very closely related with only 46 chromosomal nucleotide
      differences, 14 indels and differences in plasmid content. Both carry a
      substantial number of plasmid-borne and chromosomally encoded resistance
      determinants. Interestingly, the two differences in susceptibility between the
      isolates could be attributed to DA48896 lacking an insertion of blaOXA-181 into
      the mgrB gene that results in colistin resistance in MS6671 and SNPs affecting
      AcrAB efflux pump expression likely to result in tigecycline resistance. These
      differences between the otherwise very similar isolates indicate that strong
      selection has occurred for resistance towards these last-resort drugs and
      illustrates the trajectory of resistance evolution of OXA-181-producing versions
      of the ST147 international risk clone.

PMID- 29220375
TI  - Construction and validation of a psychometric scale to measure awareness on
      consumption of irradiated foods.
AB  - Although food irradiation has been used to ensure food safety, most consumers are
      unaware of the basic concepts of irradiation, misinterpreting information and
      demonstrating a negative attitude toward food items treated with ionizing
      radiation. This research is aimed at developing a tool to assess the awareness on
      the consumption of irradiated food. The sample was composed by employees from
      different social classes and school levels of Brazilian universities, who reflect
      the end-users of the irradiated foods, representative of the views of lay
      consumers. The total number of respondents was 614. In order to assess the
      Awareness Scale on Consumption of Irradiated Foods (ASCIF), an instrument has
      been developed and submitted to semantic tests and judge's validation. The
      instrument, that included 32 items, contemplated four construct factors: concepts
      (6 items), awareness (10 items), labeling (7 items) and safety of Irradiated
      foods (9 items). The data were collected by electronic means, through the site
      <https://pt.surveymonkey.com/>. By using exploratory factorial analysis (EFA) 4
      factors have been found. They summarize the 31 items included. These factors
      account for 64.32% of the variance of the items and the internal consistency of
      the factors has been deemed good. An Exploratory Structural Equation Modeling
      (ESEM) was conducted to evaluate the factor structure of the instrument. The
      proposed instrument has been found to meet consistency criteria as an efficient
      tool for indicating assessing potential challenges and opportunities for the
      irradiated food markets.

PMID- 29220376
TI  - C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis
      patients, and C5aR blockade attenuates leukocyte migration to synovial fluid.
AB  - Complement activation correlates to rheumatoid arthritis disease activity, and
      increased amounts of the complement split product C5a is observed in synovial
      fluids from rheumatoid arthritis patients. Blockade of C5a or its receptor (C5aR)
      is efficacious in several arthritis models. The aim of this study was to
      investigate the role of C5a and C5aR in human rheumatoid arthritis and psoriatic
      arthritis-both with respect to expression and function. Synovial fluid, blood and
      synovial samples were obtained from rheumatoid arthritis, psoriatic arthritis and
      osteoarthritis patients as a less inflammatory arthritis type, and blood from
      healthy subjects. Cells infiltrating synovial tissue were analysed by
      immunohistochemistry and flow cytometry. SF and blood were analysed for
      biomarkers by flow cytometry or ELISA. The effect of a blocking anti-human C5aR
      mAb on leukocyte migration was determined using a Boyden chamber. Appropriate
      statistical tests were applied for comparisons. C5aR+ cells were detected in most
      rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory
      control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+
      macrophages were mainly found in lymphoid aggregates in close contact with T
      cells. C5a levels were increased in both rheumatoid arthritis and psoriatic
      arthritis synovial fluid compared to osteoarthritis, and in blood from rheumatoid
      arthritis compared to healthy subjects. Neutrophil and monocyte migration to
      rheumatoid arthritis synovial fluid was significantly inhibited by anti-C5aR. The
      data support that the C5a-C5aR axis may be driving the infiltration of
      inflammatory cells into the synovial fluid and synovium in both rheumatoid and
      psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment
      target in both diseases.

PMID- 29220377
TI  - 3D diffusion model within the collagen apatite porosity: An insight to the
      nanostructure of human trabecular bone.
AB  - Bone tissue at nanoscale is a composite mainly made of apatite crystals, collagen
      molecules and water. This work is aimed to study the diffusion within bone
      nanostructure through Monte-Carlo simulations. To this purpose, an idealized
      geometric model of the apatite-collagen structure was developed. Gaussian
      probability distribution functions were employed to design the orientation of the
      apatite crystals with respect to the axes (length L, width W and thickness T) of
      a plate-like trabecula. We performed numerical simulations considering the
      influence of the mineral arrangement on the effective diffusion coefficient of
      water. To represent the hindrance of the impermeable apatite crystals on the
      water diffusion process, the effective diffusion coefficient was scaled with the
      tortuosity, the constrictivity and the porosity factors of the structure. The
      diffusion phenomenon was investigated in the three main directions of the single
      trabecula and the introduction of apatite preferential orientation allowed the
      creation of an anisotropic medium. Thus, different diffusivities values were
      observed along the axes of the single trabecula. We found good agreement with
      previous experimental results computed by means of a genetic algorithm.

PMID- 29220378
TI  - Predisposing factors to the practice of self-medication in Brazil: Results from
      the National Survey on Access, Use and Promotion of Rational Use of Medicines
      (PNAUM).
AB  - OBJECTIVE: To understand the predisposing factors that lead to the practice of
      self-medication and the factors associated with the use of medicines via self
      medication in the adult population of Brazil. METHODS: The analyzed data are part
      of the National Survey on Access, Use and Promotion of Rational Use of Medicines
      (PNAUM), a survey whose population consisted of individual residents permanently
      domiciled in urban areas in Brazil. In this work, the data references the 31 573
      respondents aged 20 or higher (76.2% of the final PNAUM sample). Poisson
      regression models with robust variance were used for estimating the independent
      effect of each variable with medicine use via self-medication. RESULTS: Of the
      interviewees, 73.6% stated they had used some medication without medical
      recommendation if they had previously used the same product; 73.8% stated they
      had used non-prescribed medicine when the medicine was already present at home;
      and 35.5% stated they had used some non-prescribed medication when they knew
      someone who had already taken the same medication. The prevalence of self
      medication was 18.3%. The variables associated with the highest probability of
      using medicine via self-medication were: geographic region within Brazil, gender,
      age group, per capita income, self-assessment of health, self-reported use of
      previously used non-prescribed medication, and self-reported use of non
      prescribed medication when that medication was already present at home.
      CONCLUSIONS: The use of medicines via self-medication in Brazil is relatively
      frequent and influenced by previous experience and familiarity with the
      medications, and is more common among women and individuals with low self
      assessment of health.

PMID- 29220379
TI  - Zebrafish skeleton development: High resolution micro-CT and FIB-SEM block
      surface serial imaging for phenotype identification.
AB  - Although bone is one of the most studied living materials, many questions about
      the manner in which bones form remain unresolved, including fine details of the
      skeletal structure during development. In this study, we monitored skeleton
      development of zebrafish larvae, using calcein fluorescence, high-resolution
      micro-CT 3D images and FIB-SEM in the block surface serial imaging mode. We
      compared calcein staining of the skeletons of the wild type and nacre mutants,
      which are transparent zebrafish, with micro-CT for the first 30 days post
      fertilization embryos, and identified significant differences. We quantified the
      bone volumes and mineral contents of bones, including otoliths, during
      development, and showed that such developmental differences, including otolith
      development, could be helpful in identifying phenotypes. In addition, high
      resolution imaging revealed the presence of mineralized aggregates in the
      notochord, before the formation of the first bone in the axial skeleton. These
      structures might play a role in the storage of the mineral. Our results highlight
      the potential of these high-resolution 3D approaches to characterize the
      zebrafish skeleton, which in turn could prove invaluable information for better
      understanding the development and the characterization of skeletal phenotypes.

PMID- 29220380
TI  - Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR
      218/Bmi1 pathway.
AB  - In cancer, glycolysis driving enzymes and their regulating microRNAs are one of
      the key focus of oncology research lately. The glycolytic enzyme hexokinase 2
      (HK2) is crucial for the Warburg effect in human glioma, the most common
      malignant brain tumor. In the present study, we studied the tumorigenic role of
      HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in
      glioma development. The HK2 expression in patient derived glioma and non
      neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines
      were assessed for their proliferation, migration and invasive potential in vitro,
      while the tumor forming potential of U87 cells was evaluated in vivo. The
      untreated cell lines served as control. The HK2 expression in (a) lentivirus
      infected, miR-218 overexpressing and (b) shRNA mediated Bmi1 silenced U87 and
      U251 glioma cell lines were quantified. Luciferase reporter assay, qRT-PCR
      analysis and WB were employed as required. The HK2 expression was significantly
      increased in glioma tissues comparing with the non neoplastic brain tissues and
      was positively correlated with the glioma grade. Silencing HK2 in glioma cell
      lines significantly decreased their proliferation, migration, invasion and
      tumorigenic abilities. Although, overexpression of miR-218 significantly
      downregulated the HK2 expression, luciferase reporter assay failed to show HK2 as
      the direct target of miR-218. A direct correlation, however, was observed between
      HK2 and Bmi-1, the direct target of miR-218. Taken together, our findings
      confirmed the tumorigenic activity of HK2 in glioma, and the involvement of the
      miR218/Bmi1 pathway in the regulation of its expression.

PMID- 29220381
TI  - Temporal distribution and genetic variants in influenza A(H1N1)pdm09 virus
      circulating in Mexico, seasons 2012 and 2013.
AB  - The 2012 and 2013 annual influenza epidemics in Mexico were characterized by
      presenting different seasonal patterns. In 2012 the A(H1N1)pdm09 virus caused a
      high incidence of influenza infections after a two-year period of low
      circulation; whereas the 2013 epidemic presented circulation of the A(H1N1)pdm09
      virus throughout the year. We have characterized the molecular composition of the
      Hemagglutinin (HA) and Neuraminidase (NA) genes of the A(H1N1)pdm09 virus from
      both epidemic seasons, emphasizing the genetic characteristics of viruses
      isolated from Yucatan in Southern Mexico. The molecular analysis of viruses from
      the 2012 revealed that all viruses from Mexico were predominantly grouped in
      clade 7. Strikingly, the molecular characterization of viruses from 2013 revealed
      that viruses circulating in Yucatan were genetically different to viruses from
      other regions of Mexico. In fact, we identified the occurrence of two genetic
      variants containing relevant mutations at both the HA and NA surface antigens.
      There was a difference on the temporal circulation of each genetic variant,
      viruses containing the mutations HA-A141T / NA-N341S were detected in May, June
      and July; whereas viruses containing the mutations HA-S162I / NA-L206S circulated
      in August and September. We discuss the significance of these novel genetic
      changes.

PMID- 29220382
TI  - Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in
      living human brain.
AB  - METHODS: Seven healthy volunteers underwent PET scans with [18F]altanserin and
      [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor
      density, a binding potential (BP) was calculated from PET data for 76 cerebral
      cortical regions. A correlation matrix was calculated between the binding
      potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional
      relationships were investigated using a bicluster analysis of the correlation
      matrix with an iterative signature algorithm. RESULTS: We identified two clusters
      of regions. The first cluster identified a distinct profile of correlation
      coefficients between 5-HT2A and D2 receptors, with the former in regions related
      to sensorimotor integration (supplementary motor area, superior parietal gyrus,
      and paracentral lobule) and the latter in most cortical regions. The second
      cluster identified another distinct profile of correlation coefficients between 5
      HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical
      regions. CONCLUSIONS: The observation of two distinct clusters in the correlation
      matrix suggests regional interactions between 5-HT2A and D2 receptors in
      sensorimotor integration and hippocampal function. A bicluster analysis of the
      correlation matrix of these neuroreceptors may be beneficial in understanding
      molecular networks in the human brain.

PMID- 29220383
TI  - Characterization of the CCT family and analysis of gene expression in Aegilops
      tauschii.
AB  - Flowering is crucial for reproductive success in flowering plant. The CCT domain
      containing genes widely participate in the regulation of flowering process in
      various plant species. So far, the CCT family in common wheat is largely unknown.
      Here, we characterized the structure, organization, molecular evolution and
      expression of the CCT genes in Aegilops tauschii, which is the D genome donor of
      hexaploid wheat. Twenty-six CCT genes (AetCCT) were identified from the full
      genome of A. tauschii and these genes were distributed on all 7 chromosomes.
      Phylogenetic analysis classified these AetCCT genes into 10 subgroups. Thirteen
      AetCCT members in group A, C, H and G achieved rapid evolution based on
      evolutionary rate analysis. The AetCCT genes respond to different exogenous
      hormones and abiotic treatments, the expression of AetCCT4, 7, 8, 11, 12, 16, 17,
      19, 21 and 22 showed a significant 24 h rhythm. This study may provide a
      reference for common wheat's evolution, domestication and evolvement rules, and
      also help us to understand the ecological adaptability of A. tauschii.

PMID- 29220384
TI  - Rope skipping increases bone mineral density at calcanei of pubertal girls in
      Hong Kong: A quasi-experimental investigation.
AB  - Bone mineral accrual during puberty is important, especially in girls, because it
      is related to reduced risks of osteoporosis in adulthood. Previous research has
      shown that jumping or plyometric exercises may be effective in increasing bone
      mineral density in adolescents. Rope skipping is a form of activity that involves
      jumping, thus regular skipping may also increase bone mineral density in pubertal
      girls. To this end, we conducted a quasi-experimental to examine the effects of
      rope skipping on girls' bone mineral density and cardiovascular fitness. 176 Hong
      Kong girls (age = 12.23 +/- 1.80 years at baseline) were recruited to take part
      in the study. Bone density at their forearms and calcanei were measured twice
      over two academic years (mean time between visits was 10.3 months). Using
      multilevel modeling analyses and adjusting for participants' height and physical
      activity, we found that girls who participated in weekly rope skipping
      activities, compared to those who did not, had higher levels of bone density at
      the calcanei (B = 0.023, p < .01). However, no differences were found for bone
      density at forearms or participants' cardiovascular fitness. The rates of change
      of these variables across time were also not significantly different. Results
      suggest that regular rope skipping may increase girls' bone density at the lower
      extremities, irrespective of the amount of self-report physical activity.
      However, further research is required to examine the potential dose-response
      relation between skipping behaviors and the measured outcomes.

PMID- 29220385
TI  - Secreted dual reporter assay with Gaussia luciferase and the red fluorescent
      protein mCherry.
AB  - The availability of a wide range of reporter proteins, which can easily be
      quantitated, has had a major impact on many fields of biomedical research. In
      some experiments with tissue culture cells, it is necessary to control for
      differences in transfection efficiency and in other expression parameters. This
      requirement has been very conveniently met with the popular dual luciferase
      assay. Its disadvantages are the requirement for cell lysis, the inability to
      analyze the same cells repeatedly, and the cost, at least in its most commonly
      used commercial format. Here we describe a novel dual reporter assay with the
      naturally secreted luciferase from Gaussia princeps as the main reporter protein
      and a secreted version of the red fluorescent protein mCherry as internal
      standard. After first measuring mCherry fluorescence in the medium, an enzyme
      buffer with coelenterazine as substrate is added to the same sample to trigger a
      glow-type luminescence of the luciferase. The simple and cheap assay can easily
      be adapted to a variety of experimental situations. As a case in point, we have
      developed a panel of Gaussia luciferase reporter genes for transcriptional
      activation assays with estrogen and glucocorticoid response elements, and with
      response elements for fusion proteins with the Gal4 DNA binding domain for use in
      mammalian cells. Our secreted dual reporter assay should be an attractive
      alternative to the currently available commercial kits.

PMID- 29220386
TI  - Does cognitive impairment impact adherence? A systematic review and meta-analysis
      of the association between cognitive impairment and medication non-adherence in
      stroke.
AB  - BACKGROUND: While medication adherence is essential for the secondary prevention
      of stroke, it is often sub-optimal, and can be compromised by cognitive
      impairment. This study aimed to systematically review and meta-analyse the
      association between cognitive impairment and medication non-adherence in stroke.
      METHODS: A systematic literature search of longitudinal and cross-sectional
      studies of adults with any stroke type, which reported on the association between
      any measure of non-adherence and cognitive impairment, was carried out according
      to PRISMA guidelines. Odds ratios and 95% confidence intervals were the primary
      measure of effect. Risk of bias was assessed using the Cochrane Bias Methods
      Group's Tool to Assess Risk of Bias in Cohort Studies, with evidence quality
      assessed according to the GRADE approach. We conducted sensitivity analyses
      according to measure of cognitive impairment, measure of medication adherence,
      population, risk of bias and adjustment for covariates. The protocol was
      registered with PROSPERO. RESULTS: From 1,760 titles and abstracts, we identified
      9 studies for inclusion. Measures of cognitive impairment varied from dementia
      diagnosis to standardised cognitive assessments. Medication adherence was
      assessed through self-report or administrative databases. The majority of studies
      were of medium risk of bias (n = 6); two studies had low risk of bias. Findings
      were mixed; when all studies were pooled, there was no evidence of an association
      between cognitive impairment and medication non-adherence post-stroke [OR (95%
      CI): 0.85 (0.66, 1.03)]. However, heterogeneity was substantial [I2 = 90.9%, p <
      .001], and the overall evidence quality was low. CONCLUSIONS: Few studies have
      explored associations between cognitive impairment and medication adherence post
      stroke, with substantial heterogeneity in study populations, and definitions and
      assessments of non-adherence and cognitive impairment. Further research using
      clear, standardised and objective assessments is needed to clarify the
      association between cognitive impairment and medication non-adherence in stroke.

PMID- 29220388
TI  - A three-month longitudinal study of changes in day/night serum total antioxidant
      capacity in paranoid schizophrenia.
AB  - Free radicals and an oxidant/antioxidant imbalance have been involved in the
      schizophrenia pathophysiology. The total antioxidant capacity (TAC) is a measure
      of the antioxidant capacity of a system. Day/night changes are a biological
      characteristic of hormones such as melatonin or cortisol. There is little
      information about TAC day/night changes in schizophrenia patients. The aim of
      this research is to study if there are day/night changes in serum TAC levels of
      schizophrenia patients. Thirty-two DSM-IV schizophrenia paranoid patients were
      studied. Blood was sampled at 12:00 and 00:00 h at admission, discharge and three
      months after hospital discharge (TMAHD). TAC results are expressed as mmol of
      Trolox/L. Patients did not have day/night TAC differences at admission (12:00:
      0.67+/-0.12 vs. 00:00: 0.61+/-0.14, p>0.14) or discharge (12:00: 0.65+/-0.15 vs.
      00:00: 0.65+/-0.12, p>0.99). At TMHD, patients had significantly higher TAC
      levels at midday than midnight (12:00: 0.83+/-0.10 vs. 00:00: 0.74+/-0.12,
      p<0.006) as it has been reported in healthy subjects. There were no significant
      TAC differences at 12.00 and 00:00 between admission and discharge. At TMAHD,
      patients had significantly higher TAC levels than at admission and discharge,
      both at 12:00 and 00:00 h. In conclusion, the absence of day/night serum TAC
      changes when clinically relapsed and the normalization of day/night serum TAC
      changes at TMHD can be considered as a biological marker of schizophrenia
      evolution.

PMID- 29220387
TI  - PsrA controls the synthesis of the Pseudomonas aeruginosa quinolone signal via
      repression of the FadE homolog, PA0506.
AB  - Pseudomonas aeruginosa is a ubiquitous, Gram-negative opportunistic pathogen that
      can cause disease in various sites within the human body. This bacterium is a
      major source of nosocomial infections that are often difficult to treat due to
      high intrinsic antibiotic resistance and coordinated virulence factor production.
      P. aeruginosa utilizes three cell-to-cell signaling systems to regulate numerous
      genes in response to cell density. One of these systems utilizes the small
      molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]) as a
      signal that acts as a co-inducer for the transcriptional regulator PqsR.
      Quinolone signaling is required for virulence in multiple infection models, and
      PQS is produced during human infections, making this system an attractive target
      for potential drug development. In this study we have examined the role of a TetR
      type transcriptional regulator, PsrA, in the regulation of PQS production by P.
      aeruginosa. Previous studies showed that PsrA regulates genes of the fatty acid
      beta-oxidation pathway, including PA0506, which encodes a FadE homolog. In this
      report, we show that deletion of psrA resulted in a large decrease in PQS
      production and that co-deletion of PA0506 allowed PQS production to be restored
      to a wild type level. We also found that PQS production could be restored to the
      psrA mutant by the addition of oleic or octanoic acid. Taken together, our data
      suggest that psrA positively affects PQS production by repressing the
      transcription of PA0506, which leads to a decrease in the conversion of acyl-CoA
      compounds to enoyl-CoA compounds, thereby allowing some octanoyl-CoA to escape
      the beta-oxidation pathway and serve as a PQS precursor.

PMID- 29220389
TI  - Association of genetic variations in FOXO3 gene with susceptibility to noise
      induced hearing loss in a Chinese population.
AB  - Noise induced hearing loss (NIHL), a multifactorial disease involving both
      genetic and environmental factors, is one of the most important occupational
      health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have
      not been illuminated. This research was conducted to explore the effects of FOXO3
      polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial
      workers from one textile factory of east China were recruited to participate in
      the current research. Venous blood was collected, questionnaire and pure-tone
      audiometry (PTA) was conducted by specialist physicians. Then, we performed
      genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in
      FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects
      of genotype and its interactions were evaluated. Our results revealed that
      individuals with the G allele of rs2802292, G allele of rs10457180, T allele of
      rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and
      others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09
      respectively) are associated with an increased risk of NIHL in a Chinese
      population. Stratified analysis showed that an increased NIHL risk was found in
      the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180
      AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor
      dimensionality reduction analysis indicated that rs10457180, rs2802292, and
      rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53).
      The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene
      are associated with an increased risk of NIHL in a Chinese population and have
      potential to be biomarkers for noise exposed workers.

PMID- 29220390
TI  - MALDI MSI of MeLiM melanoma: Searching for differences in protein profiles.
AB  - BACKGROUND: Treatment of advanced cutaneous melanoma remains challenging, and new
      data on melanoma biology are required. The most widely accepted criteria for the
      prognostic evaluation of melanoma are histopathological and clinical parameters,
      and the identification of additional tumor markers is thus of paramount
      importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging
      (MALDI MSI), an important tool in cancer research, is useful for unraveling the
      molecular profile of melanoma. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we
      used the melanoma-bearing Libechov minipig (MeLiM), a unique animal model that
      allows observation of the complete spontaneous regression of invasive cutaneous
      melanoma, to investigate i) the differences between melanoma and healthy skin
      protein profiles and ii) the proteins potentially involved in spontaneous
      regression. The MeLiM tissues were cryosected, histologically characterized,
      analyzed by MALDI MSI, and immunohistologically stained. Multivariate statistical
      analyses of the MALDI MSI data revealed ten relevant m/z ions, of which the
      expression levels varied significantly among the studied MeLiM tissues. These ion
      peaks were used to create mass ion images/maps and visualize the differences
      between tumor and healthy skin specimens, as well as among histologically
      characterized tissue regions. CONCLUSIONS/SIGNIFICANCE: Protein profiles
      comprising ten statistically significant mass ion peaks useful for
      differentiating cutaneous melanoma and healthy skin tissues were determined.
      Peaks at m/z 3044, 6011, 6140 and 10180 were overexpressed in melanoma compared
      with healthy skin tissue. More specifically, m/z 6140 was expressed at
      significantly (p < 0.05) higher levels in normally growing melanoma regions than
      in regions with early and late spontaneous regression. This study demonstrates
      the clinical utility of MALDI MSI for the analysis of tissue cryosections at a
      molecular level.

PMID- 29220391
TI  - The meaning of a poor childbirth experience - A qualitative phenomenological
      study with women in Rwanda.
AB  - OBJECTIVE: Being pregnant and giving birth is a pivotal life event and one that a
      woman ordinarily remembers for most of her life. A negative childbirth experience
      can affect a woman's health well beyond the episode of the labour and birth
      itself. This study explored the meaning of a poor childbirth experience, as
      expressed by women who had given birth in Rwanda. METHODS: In a cross-sectional
      household study conducted in Northern Province and in Kigali City, the capital of
      Rwanda, a structured questionnaire was answered by women who had given birth one
      to 13 months earlier. One question, answered by 898 women, asked them to rate
      their overall experience of childbirth from 0 (very bad) to 10 (very good). Of
      these, 28 women (3.1%) who had rated their childbirth experience as bad (<= 4)
      were contacted for individual interviews. Seventeen of these women agreed to
      participate in individual in-depth interviews. The texts were analysed with a
      reflective lifeworld approach. RESULTS: The essential meaning of a "poor"
      childbirth experience was that the women had been exposed to disrespectful care,
      constituted by neglect, verbal or physical abuse, insufficient information, and
      denial of their husband as a companion. The actions of carers included
      abandonment, humiliation, shaming and insult, creating feelings of insecurity,
      fear and distrust in the women. Two of the women did not report any experience of
      poor care; their low rating was related to having suffered from medical
      complications. CONCLUSION: It is challenging that the main finding is that women
      are exposed to disrespectful care. In an effort to provide an equitable and high
      quality maternal health care system in Rwanda, there is a need to focus on
      activities to implement respectful, evidence-based care for all. One such
      activity is to develop and provide education programmes for midwives and nurses
      about professional behaviour when caring for and working with women during labour
      and birth.

PMID- 29220393
TI  - Process service quality evaluation based on Dempster-Shafer theory and support
      vector machine.
AB  - Human involvement influences traditional service quality evaluations, which
      triggers an evaluation's low accuracy, poor reliability and less impressive
      predictability. This paper proposes a method by employing a support vector
      machine (SVM) and Dempster-Shafer evidence theory to evaluate the service quality
      of a production process by handling a high number of input features with a low
      sampling data set, which is called SVMs-DS. Features that can affect production
      quality are extracted by a large number of sensors. Preprocessing steps such as
      feature simplification and normalization are reduced. Based on three individual
      SVM models, the basic probability assignments (BPAs) are constructed, which can
      help the evaluation in a qualitative and quantitative way. The process service
      quality evaluation results are validated by the Dempster rules; the decision
      threshold to resolve conflicting results is generated from three SVM models. A
      case study is presented to demonstrate the effectiveness of the SVMs-DS method.

PMID- 29220392
TI  - Safety and efficacy of the PrePex device in HIV-positive men: A single-arm study
      in Zimbabwe.
AB  - METHODS: We aimed to determine if the adverse event (AE) rate was non-inferior to
      an AE rate of 2%, a rate considered the global standard of MC safety. Study
      procedures, AE definitions, and study staff were unchanged from previous PrePex
      Zimbabwe trials. After PrePex placement and removal, weekly visits assessed wound
      healing. Men returned on Day 90. Safety was defined as occurrence of moderate and
      serious clinical AEs. Efficacy was defined as ability to reach the endpoint of
      complete circumcision. RESULTS: Among 400 healthy, HIV-positive, consenting
      adults, median age was 40 years (IQR: 34, 46); 79.5% in WHO stage 2; median CD4
      was 336.5c/MUl (IQR: 232, 459); 337 (85%) on anti-retroviral therapy. Among 385
      (96%) observed completely healed, median days to complete healing was 42 (IQR: 35
      49). There was no association between time to healing and CD4 (p = 0.66). Four
      study-related severe AEs and no moderate AEs were reported: severe/moderate AE
      rate of 1.0% (95% CI: 0.27% to 2.5). This was non-inferior to 2% AEs (p =
      0.0003). All AEs were device displacements resulting in surgical MC and,
      subsequently, complete healing. CONCLUSION: Male circumcision among healthy, HIV
      positive men using PrePex is safe and effective. Reducing the barrier of HIV
      testing while improving counseling for safer sex practices among all MC clients
      could increase MC uptake and avert more HIV infections.

PMID- 29220394
TI  - A systematic approach to evaluate the influence of environmental conditions on
      eDNA detection success in aquatic ecosystems.
AB  - The use of environmental DNA (eDNA) to determine the presence and distribution of
      aquatic organisms has become an important tool to monitor and investigate
      freshwater communities. The successful application of this method in the field,
      however, is dependent on the effectiveness of positive DNA verification, which is
      influenced by site-specific environmental parameters. Factors affecting eDNA
      concentrations in aquatic ecosystems include flow conditions, and the presence of
      substances that possess DNA-binding properties or inhibitory effects. In this
      study we investigated the influence of different environmental parameters on the
      detection success of eDNA using the invasive goby Neogobius melanostomus. In a
      standardized laboratory setup, different conditions of flow, sediment-properties,
      and fish density were compared, as well as different potential natural inhibitors
      such as algae, humic substances, and suspended sediment particles. The presence
      of sediment was mainly responsible for lower eDNA detection in the water samples,
      regardless of flow-through or standing water conditions and a delayed release of
      eDNA was detected in the presence of sediment. Humic substances had the highest
      inhibitory effect on eDNA detection followed by algae and siliceous sediment
      particles. The results of our study highlight that a successful application of
      eDNA methods in field surveys strongly depends on site-specific conditions, such
      as water flow conditions, sediment composition, and suspended particles. All
      these factors should be carefully considered when sampling, analyzing, and
      interpreting eDNA detection results.

PMID- 29220395
TI  - MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting
      TIMP2.
AB  - MicroRNAs (miRNAs) are important regulators of pathobiological processes in
      various cancer. In the present study, we demonstrated that miR-93 expression was
      significantly up-regulated in gastric cancer tissues compared with that in
      matched normal mucosal tissues. High expression of miR-93 was significantly
      associated with lymph node metastasis and tumor-node-metastasis (TNM) stage.
      Functionally, ectopic expression of miR-93 promoted cell proliferation,
      migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle
      arrest in vitro, and promoted tumor formation in vivo. We further identified that
      tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by
      using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore,
      knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in
      gastric cancer cells with that transfected with miR-93 mimics. Our findings
      indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis
      by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and
      therapeutic target for treatment of gastric cancer.

PMID- 29220396
TI  - Improved approach for electric vehicle rapid charging station placement and
      sizing using Google maps and binary lightning search algorithm.
AB  - The electric vehicle (EV) is considered a premium solution to global warming and
      various types of pollution. Nonetheless, a key concern is the recharging of EV
      batteries. Therefore, this study proposes a novel approach that considers the
      costs of transportation loss, buildup, and substation energy loss and that
      incorporates harmonic power loss into optimal rapid charging station (RCS)
      planning. A novel optimization technique, called binary lightning search
      algorithm (BLSA), is proposed to solve the optimization problem. BLSA is also
      applied to a conventional RCS planning method. A comprehensive analysis is
      conducted to assess the performance of the two RCS planning methods by using the
      IEEE 34-bus test system as the power grid. The comparative studies show that the
      proposed BLSA is better than other optimization techniques. The daily total cost
      in RCS planning of the proposed method, including harmonic power loss, decreases
      by 10% compared with that of the conventional method.

PMID- 29220397
TI  - Desethylamiodarone-A metabolite of amiodarone-Induces apoptosis on T24 human
      bladder cancer cells via multiple pathways.
AB  - Bladder cancer (BC) is a common malignancy of the urinary tract that has a higher
      frequency in men than in women. Cytostatic resistance and metastasis formation
      are significant risk factors in BC therapy; therefore, there is great interest in
      overcoming drug resistance and in initiating research for novel chemotherapeutic
      approaches. Here, we suggest that desethylamiodarone (DEA)-a metabolite of
      amiodarone-may have cytostatic potential. DEA activates the collapse of
      mitochondrial membrane potential (detected by JC-1 fluorescence), and induces
      cell death in T24 human transitional-cell bladder carcinoma cell line at
      physiologically achievable concentrations. DEA induces cell cycle arrest in the
      G0/G1 phase, which may contribute to the inhibition of cell proliferation, and
      shifts the Bax/Bcl-2 ratio to initiate apoptosis, induce AIF nuclear
      translocation, and activate PARP-1 cleavage and caspase-3 activation. The major
      cytoprotective kinases-ERK and Akt-are inhibited by DEA, which may contribute to
      its cell death-inducing effects. DEA also inhibits the expression of B-cell
      specific Moloney murine leukemia virus integration site 1 (BMI1) and reduces
      colony formation of T24 bladder carcinoma cells, indicating its possible
      inhibitory effect on metastatic potential. These data show that DEA is a novel
      anti-cancer candidate of multiple cell death-inducing effects and metastatic
      potential. Our findings recommend further evaluation of its effects in clinical
      studies.

PMID- 29220398
TI  - A minimally invasive optical trapping system to understand cellular interactions
      at onset of an immune response.
AB  - T-cells and antigen presenting cells are an essential part of the adaptive immune
      response system and how they interact is crucial in how the body effectively
      fights infection or responds to vaccines. Much of the experimental work studying
      interaction forces between cells has looked at the average properties of bulk
      samples of cells or applied microscopy to image the dynamic contact between these
      cells. In this paper we present a novel optical trapping technique for
      interrogating the force of this interaction and measuring relative interaction
      forces at the single-cell level. A triple-spot optical trap is used to directly
      manipulate the cells of interest without introducing foreign bodies such as beads
      to the system. The optical trap is used to directly control the initiation of
      cell-cell contact and, subsequently to terminate the interaction at a defined
      time point. The laser beam power required to separate immune cell pairs is
      determined and correlates with the force applied by the optical trap. As proof of
      concept, the antigen-specific increase in interaction force between a dendritic
      cell and a specific T-cell is demonstrated. Furthermore, it is demonstrated that
      this interaction force is completely abrogated when T-cell signalling is blocked.
      As a result the potential of using optical trapping to interrogate cellular
      interactions at the single cell level without the need to introduce foreign
      bodies such as beads is clearly demonstrated.

PMID- 29220399
TI  - "What they see is what you get": Prescribing antibiotics for respiratory tract
      infections in primary care: Do high prescribers diagnose differently? An analysis
      of German routine data.
AB  - BACKGROUND: Characteristics of high and low prescribers of antibiotics in German
      primary care were analysed using population data. We aimed to evaluate
      differences in prescribing rates and factors being associated with high
      prescribing, and whether high prescribers made the diagnosis of perceived
      bacterial infections more often. METHODS: Routine data were provided by the
      Bavarian Association of Statutory Health Insurance Physicians. Routine data are
      delivered by primary care practices on a quarterly basis. We analysed data from
      2011 and 2012. Patients older than 15 years with respiratory tract infections
      consulting a primary care physician were selected (6.647 primary care practices).
      Patient and physician characteristics associated with high prescribing were
      identified using stepwise logistic regression. RESULTS: Mean prescribing rate of
      antibiotics was 24.9%. Prescribing rate for high prescribers was 43.5% compared
      to 8.5% for low prescribers. High prescribers made the diagnosis of perceived
      bacterial infections more often (Mhigh = 64.5%, Mlow = 45.2%). In the adjusted
      regression model, perceived bacterial infections were strongly associated with
      high prescribing (OR = 13.9, 95% CI [10.2, 18.8]). Treating patients with
      comorbidities was associated with lower prescribing of antibiotics (OR = 0.6, 95%
      CI [0.4, 0.8]). High prescribers had a higher practice volume, a higher degree of
      prescribing dominance, and were situated more often in deprived areas and in
      rural settings. INTERPRETATION: Compared to findings of studies in other European
      countries, prescribing rates were low. There was a considerable difference
      between prescribing rates of high and low prescribers. Diagnostic labelling was
      the best predictor for high prescribing. Current guidelines recommend considering
      antibiotic treatment for patients with co-morbidities. In our study, treating a
      large number of high-risk patients was not associated with high prescribing.

PMID- 29220400
TI  - Social structure, opportunistic punishment and the evolution of honest signaling.
AB  - Honest signaling is generally taken to be a necessary pre-condition for a stable
      signaling system, because deceptive signaling at a high enough rate should cause
      receivers to ignore the signal, which in turn undermines the utility of sending
      signals. Deception is normally thought to occur because of benefits it has to the
      deceiver. This raises the question of why signaling systems should exist and
      persist over time, especially in cases in which the interests of the senders and
      receivers are not well aligned. Punishment has been seen as a way of imposing
      costs on deceptive signalers. We investigate the effects of opportunistic-that
      is, non-altruistic punishment-on the evolution of an honest signaling system. Our
      model is based on research done on social insects. We model a society of agents,
      divided into three castes differing in aggressiveness. Under severe punishment
      deception is indeed asymptotically eliminated. Under somewhat less severe
      punishment, deception persists and the rates of deception correlate with social
      structure. We find that social structure robustly mediates the level of deception
      under regimes of punishment and that this is evident except in the most stringent
      of punishment regimes.

PMID- 29220401
TI  - Contour recognition of complex leaf shapes.
AB  - The leaf shape is an important taxonomic character. Compared to the classic
      morphological leaf features such as veins, margin indentations, sinuses, etc.,
      the shape is simpler to obtain by using the 'magic wand' or other contouring
      tools that are available in most of imaging applications. The only exception is
      when leaves develop large lobes that get in touch or overlap each other, as the
      presence of hidden or closed portions of the leaf border precludes the
      application of automatic methods and forces the leaf contour to be traced
      manually. This is a time consuming and relatively accurate operation that,
      nevertheless, can not be avoided, as overlapping lobes are characteristic
      features of the leaves of several plant species and varieties. The method
      described in the paper overcomes this problem as it allows the leaf contour to be
      achieved even in the presence of touching or overlapping lobes. The method
      involves three steps: (1) the acquisition of leaf images using a
      transilluminator, (2) a two-level image segmentation that allows all leaf
      components (blade, overlapping lobes and closed sinuses) to be represented in a
      single binary image, and (3) the contouring and concatenation of all binary
      outlines in a single, self-intersecting closed contour that reproduces accurately
      the leaf shape. The method can be extended to acquire the shape of leaves of
      herbarium specimens, that are often overlapped but can not be easily handled and
      repositioned because of their extreme fragility and relevant taxonomic value.

PMID- 29220402
TI  - Bodily motion fluctuation improves reaching success rate in a neurophysical agent
      via geometric-stochastic resonance.
AB  - Organisms generate a variety of noise types, including neural noise, sensory
      noise, and noise resulting from fluctuations associated with movement. Sensory
      and neural noises are known to induce stochastic resonance (SR), which improves
      information transfer to the subjects control systems, including the brain. As a
      consequence, sensory and neural noise provide behavioral benefits, such as
      stabilization of posture and enhancement of feeding efficiency. In contrast, the
      benefits of fluctuations in the movements of a biological system remain largely
      unclear. Here, we describe a novel type of noise-induced order (NIO) that is
      realized by actively exploiting the motion fluctuations of an embodied system. In
      particular, we describe the theoretical analysis of a feedback-controlled
      embodied agent system that has a geometric end-effector. Furthermore, through
      several numerical simulations we demonstrate that the ratio of successful reaches
      to goal positions and capture of moving targets are improved by the exploitation
      of motion fluctuations. We report that reaching success rate improvement (RSRI)
      is based on the interaction of the geometric size of an end-effector, the agents
      motion fluctuations, and the desired motion frequency. Therefore, RSRI is a
      geometrically induced SR-like phenomenon. We also report an interesting result
      obtained through numerical simulations indicating that the agents neural and
      motion noise must be optimized to match the prey's motion noise in order to
      maximize the capture rate. Our study provides a new understanding of body motion
      fluctuations, as they were found to be the active noise sources for a behavioral
      NIO.

PMID- 29220403
TI  - Correction: Modelling innovation performance of European regions using multi
      output neural networks.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185755.].

PMID- 29220404
TI  - PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68
      positive cells in breast tumor development.
AB  - CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and
      are associated with decreased survival rates in patients with cancer, including
      breast cancer. Non-specific models of macrophage ablation reduce the number of
      TAMs and limit the development of mammary tumors. However, the lack of
      specificity and side effects associated with these models compromise their
      reliability. We hypothesized that specific and controlled macrophage depletion
      would provide precise data on the effects of reducing TAM numbers on tumor
      development. In this study, the MacLow mouse model of doxycycline-inducible and
      selective CD68+ macrophage depletion was crossed with the murine mammary tumor
      virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous
      ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline
      treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding
      tumors by 43%. Reducing the number of macrophages by this level delayed tumor
      progression, generated less proliferative tumors, decreased the vascularization
      of carcinomas and down-regulated the expression of many pro-angiogenic genes.
      These results demonstrate that depleting CD68+ macrophages in an inducible and
      selective manner delays the development of mammary tumors and that the PyMT
      MacLow model is a useful and unique tool for studying the role of TAMs in breast
      cancer.

PMID- 29220405
TI  - Maaqwi cascadensis: A large, marine diving bird (Avialae: Ornithurae) from the
      Upper Cretaceous of British Columbia, Canada.
AB  - Mesozoic bird fossils from the Pacific Coast of North America are rare, but small
      numbers are known from the Late Cretaceous aged sediments of Hornby Island,
      British Columbia. Most are unassociated fragments that offer little information,
      but additional preparation of a large coracoid has revealed more details of its
      structure, as well as three associated wing bones. Phylogenetic analysis suggests
      that Maaqwi cascadensis, gen. et sp. nov. represents a derived crown or near
      crown member of Ornithurae, and specifically suggests affinities with Vegaviidae.
      M. cascadensis is characterized by large size, and regressions based on
      dimensions of the coracoid suggest a large bird, with an estimated body mass of
      approximately 1.5 kilograms. The bones are robust, with thick walls, suggesting
      that M. cascadensis was a bird adapted for diving, similar to modern loons and
      grebes. The wings are short, while the coracoid is unusually short and broad,
      similar to modern loons. Along with the Ichthyornithes and Hesperornithes, M.
      cascadensis and Vegaviidae appear to represent a third clade of bird that evolved
      to exploit marine habitats in the Late Cretaceous, one specialized for foot
      propelled diving and rapid cruising flight over water.

PMID- 29220406
TI  - Excessively low salt diet damages the heart through activation of cardiac (pro)
      renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: A high salt intake causes hypertension and leads to cardiovascular
      disease. Therefore, a low salt diet is now recommended to prevent hypertension
      and cardiovascular disease. However, it is still unknown whether an excessively
      low salt diet is beneficial or harmful for the heart. METHODS: Wistar Kyoto rats
      (WKYs) and spontaneously hypertensive rats (SHRs) received normal salt chow (0.9%
      salt diet) and excessively low salt chow (0.01% salt diet referred to as saltless
      diet) for 8 weeks from 8 to 16 weeks of age. The effects of the excessively low
      salt diet on the cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and
      sympatho-adrenal systems were investigated. RESULTS: The excessively low salt
      diet did not affect the systolic blood pressure but significantly increased the
      heart rate both in WKYs and SHRs. The excessively low salt diet significantly
      elevated plasma renin activity, plasma angiotensin I, II and aldosterone
      concentrations, and plasma noradrenaline and adrenaline concentrations both in
      WKYs and SHRs. Cardiac expressions of renin, prorenin, (P)RR, angiotensinogen,
      and angiotensin II AT1 receptor and phosphorylated (p)-ERK1/2, p-HSP27, p-38MAPK,
      and TGF-beta1 were significantly enhanced by the excessively low salt diet in
      both WKYs and SHRs. The excessively low salt diet accelerated cardiac
      interstitial and perivascular fibrosis and increased the cardiomyocyte size and
      interventricular septum thickness in WKYs and SHRs but the extent was greater in
      SHRs. CONCLUSION: An excessively low salt diet damages the heart through
      activation of plasma renin-angiotensin-aldosterone and sympatho-adrenal systems
      and activation of cardiac (P)RR and angiotensin II AT1 receptor and their
      downstream signals both in WKYs and SHRs.

PMID- 29220407
TI  - Respiratory resistance and reactance in adults with sickle cell anemia:
      Correlation with functional exercise capacity and diagnostic use.
AB  - BACKGROUND: The improvement in sickle cell anemia (SCA) care resulted in the
      emergence of a large population of adults living with this disease. The
      mechanisms of lung injury in this new population are largely unknown. The forced
      oscillation technique (FOT) represents the current state-of-the-art in the
      assessment of lung function. The present work uses the FOT to improve our
      knowledge about the respiratory abnormalities in SCA, evaluates the associations
      of FOT with the functional exercise capacity and investigates the early detection
      of respiratory abnormalities. METHODOLOGY/PRINCIPAL FINDINGS: Spirometric
      classification of restrictive abnormalities resulted in three categories:
      controls (n = 23), patients with a normal exam (n = 21) and presenting pulmonary
      restriction (n = 24). FOT analysis showed that, besides restrictive changes
      (reduced compliance; p<0.001), there is also an increase in respiratory
      resistance (p<0.001) and ventilation heterogeneity (p<0.01). FOT parameters are
      associated with functional exercise capacity (R = -0.38), pulmonary diffusion (R
      = 0.66), respiratory muscle performance (R = 0.41), pulmonary volumes (R = 0.56)
      and airway obstruction (R = 0.54). The diagnostic accuracy was evaluated by
      investigating the area under the receiver operating characteristic curve (AUC). A
      combination of FOT and machine learning (ML) classifiers showed adequate
      diagnostic accuracy in the detection of early respiratory abnormalities (AUC =
      0.82). CONCLUSIONS: In this study, the use of FOT showed that adults with SCA
      develop a mixed pattern of respiratory disease. Changes in FOT parameters are
      associated with functional exercise capacity decline, abnormal pulmonary
      mechanics and diffusion. FOT associated with ML methods accurately diagnosed
      early respiratory abnormalities. This suggested the potential utility of the FOT
      and ML clinical decision support systems in the identification of respiratory
      abnormalities in patients with SCA.

PMID- 29220408
TI  - Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they
      reliable models to study Type 2 Diabetes mellitus?
AB  - Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects
      different cultures throughout the world. T2DM occurs under the influence of three
      main factors: the genetic background, environmental and behavioral components.
      Obesity is strongly associated to the development of T2DM in the occident, while
      in the orient most of the diabetic patients are considered lean. Genetics may be
      a key factor in the development of T2DM in societies where obesity is not a
      recurrent public health problem. Herein, two different models of rats were used
      to understand their differences and reliability as experimental models to study
      the pathophysiology of T2DM, in two different approaches: the genetic (GK rats)
      and the environmental (HFD-induced obese rats) influences. GK rats were resistant
      to weight gain even though food/energy consumption (relative to body weight) was
      higher in this group. HFD, on the other hand, induced obesity in Wistar rats.
      White adipose tissue (WAT) expansion in this group was accompanied by immune
      cells infiltration, inflammation and insulin resistance. GK rats also presented
      WAT inflammation and insulin resistance; however, no immune cells infiltration
      was observed in the WAT of this group. Liver of HFD group presented fat
      accumulation without differences in inflammatory cytokines content, while liver
      of GK rats didn't present fat accumulation, but showed an increase of IL-6 and IL
      10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT.
      Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats,
      which presented higher content of basal phosphorylation of GSK-3beta. Our results
      demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was
      not sufficient to develop T2DM. In contrast, GK rats presented all the typical
      hallmarks of T2DM, such as insulin resistance, defective insulin production,
      fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the
      given time point of this study, we may conclude that only GK rats shown to be a
      reliable model to study T2DM.

PMID- 29220409
TI  - Acquisition of functions on the outer capsid surface during evolution of double
      stranded RNA fungal viruses.
AB  - Unlike their counterparts in bacterial and higher eukaryotic hosts, most fungal
      viruses are transmitted intracellularly and lack an extracellular phase. Here we
      determined the cryo-EM structure at 3.7 A resolution of Rosellinia necatrix
      quadrivirus 1 (RnQV1), a fungal double-stranded (ds)RNA virus. RnQV1, the type
      species of the family Quadriviridae, has a multipartite genome consisting of four
      monocistronic segments. Whereas most dsRNA virus capsids are based on dimers of a
      single protein, the ~450-A-diameter, T = 1 RnQV1 capsid is built of P2 and P4
      protein heterodimers, each with more than 1000 residues. Despite a lack of
      sequence similarity between the two proteins, they have a similar alpha-helical
      domain, the structural signature shared with the lineage of the dsRNA bluetongue
      virus-like viruses. Domain insertions in P2 and P4 preferential sites provide
      additional functions at the capsid outer surface, probably related to enzyme
      activity. The P2 insertion has a fold similar to that of gelsolin and profilin,
      two actin-binding proteins with a function in cytoskeleton metabolism, whereas
      the P4 insertion suggests protease activity involved in cleavage of the P2 383
      residue C-terminal region, absent in the mature viral particle. Our results
      indicate that the intimate virus-fungus partnership has altered the capsid genome
      protective and/or receptor-binding functions. Fungal virus evolution has tended
      to allocate enzyme activities to the virus capsid outer surface.

PMID- 29220410
TI  - Cleavage of osmosensitive transcriptional factor NFAT5 by Coxsackieviral protease
      2A promotes viral replication.
AB  - Nuclear factor of activated T cells 5 (NFAT5)/Tonicity enhancer binding protein
      (TonEBP) is a transcription factor induced by hypertonic stress in the kidney.
      However, the function of NFAT5 in other organs has rarely been studied, even
      though it is ubiquitously expressed. Indeed, although NFAT5 was reported to be
      critical for heart development and function, its role in infectious heart
      diseases has remained obscure. In this study, we aimed to understand the
      mechanism by which NFAT5 interferes with infection of Coxsackievirus B3 (CVB3), a
      major cause of viral myocarditis. Our initial results demonstrated that although
      the mRNA level of NFAT5 remained constant during CVB3 infection, NFAT5 protein
      level decreased because the protein was cleaved. Bioinformatic prediction and
      verification of the predicted site by site-directed mutagenesis experiments
      determined that the NFAT5 protein was cleaved by CVB3 protease 2A at Glycine 503.
      Such cleavage led to the inactivation of NFAT5, and the 70-kDa N-terminal
      cleavage product (p70-NFAT5) exerted a dominant negative effect on the full
      length NFAT5 protein. We further showed that elevated expression of NFAT5 to
      counteract viral protease cleavage, especially overexpression of a non-cleavable
      mutant of NFAT5, significantly inhibited CVB3 replication. Ectopic expression of
      NFAT5 resulted in elevated expression of inducible nitric oxide synthase (iNOS),
      a factor reported to inhibit CVB3 replication. The necessity of iNOS for the anti
      CVB3 effect of NFAT5 was supported by the observation that inhibition of iNOS
      blocked the anti-CVB3 effect of NFAT5. In a murine model of viral myocarditis, we
      observed that treatment with hypertonic saline or mannitol solution upregulated
      NFAT5 and iNOS expression, inhibited CVB3 replication and reduced tissue damage
      in the heart. Taken together, our data demonstrate that the anti-CVB3 activity of
      NFAT5 is impaired during CVB3 infection due to 2A-mediated cleavage of NFAT5.
      Thus induction of NFAT5 by hypertonic agents may be a promising strategy for the
      development of anti-CVB3 therapeutics.

PMID- 29220411
TI  - Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury,
      attenuates inflammation, and improves antioxidant defenses in a rat stroke model.
AB  - The purpose of the present experiment was to investigate whether
      hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome
      via the activation of antioxidative activities, anti-inflammation, and anti
      apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with
      cerebral I/R injury were induced by a transient middle cerebral artery occlusion
      (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly
      divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg
      HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The
      animals were immediately injected with HHC by an intraperitoneal administration
      at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were
      tested for neurological deficits, and the pathology of the brain was studied by
      2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E)
      staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL)
      staining. In addition, the brain tissues were prepared for protein extraction for
      Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay,
      a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione
      peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores
      and the infarct volume were significantly reduced in the HHC-treated rats at all
      doses compared to the vehicle group. Treatment with HHC significantly attenuated
      oxidative stress and inflammation, with a decreased level of MDA and NO and a
      decreased expression of NF-kappaB (p65) and cyclooxygenase-2 (COX-2) in the I/R
      rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme
      oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the
      superoxide dismutase (SOD) activity. Moreover, the HHC treatment also
      significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3
      and an increase in Bcl-XL, which was in accordance with a decrease in the
      apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from
      cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis.
      The antioxidant properties of HHC may play an important role in improving
      functional outcomes and may offer significant neuroprotection against I/R damage.

PMID- 29220412
TI  - Do managed bees have negative effects on wild bees?: A systematic review of the
      literature.
AB  - Managed bees are critical for crop pollination worldwide. As the demand for
      pollinator-dependent crops increases, so does the use of managed bees. Concern
      has arisen that managed bees may have unintended negative impacts on native wild
      bees, which are important pollinators in both agricultural and natural
      ecosystems. The goal of this study was to synthesize the literature documenting
      the effects of managed honey bees and bumble bees on wild bees in three areas:
      (1) competition for floral and nesting resources, (2) indirect effects via
      changes in plant communities, including the spread of exotic plants and decline
      of native plants, and (3) transmission of pathogens. The majority of reviewed
      studies reported negative effects of managed bees, but trends differed across
      topical areas. Of studies examining competition, results were highly variable
      with 53% reporting negative effects on wild bees, while 28% reported no effects
      and 19% reported mixed effects (varying with the bee species or variables
      examined). Equal numbers of studies examining plant communities reported positive
      (36%) and negative (36%) effects, with the remainder reporting no or mixed
      effects. Finally, the majority of studies on pathogen transmission (70%) reported
      potential negative effects of managed bees on wild bees. However, most studies
      across all topical areas documented the potential for impact (e.g. reporting the
      occurrence of competition or pathogens), but did not measure direct effects on
      wild bee fitness, abundance, or diversity. Furthermore, we found that results
      varied depending on whether managed bees were in their native or non-native
      range; managed bees within their native range had lesser competitive effects, but
      potentially greater effects on wild bees via pathogen transmission. We conclude
      that while this field has expanded considerably in recent decades, additional
      research measuring direct, long-term, and population-level effects of managed
      bees is needed to understand their potential impact on wild bees.

PMID- 29220413
TI  - Reinforcement learning account of network reciprocity.
AB  - Evolutionary game theory predicts that cooperation in social dilemma games is
      promoted when agents are connected as a network. However, when networks are fixed
      over time, humans do not necessarily show enhanced mutual cooperation. Here we
      show that reinforcement learning (specifically, the so-called Bush-Mosteller
      model) approximately explains the experimentally observed network reciprocity and
      the lack thereof in a parameter region spanned by the benefit-to-cost ratio and
      the node's degree. Thus, we significantly extend previously obtained numerical
      results.

PMID- 29220414
TI  - Detection of spontaneous pulse using the acceleration signals acquired from CPR
      feedback sensor in a porcine model of cardiac arrest.
AB  - BACKGROUND: Reliable detection of return of spontaneous circulation with minimal
      interruptions of chest compressions is part of high-quality cardiopulmonary
      resuscitation (CPR) and routinely done by checking pulsation of carotid arteries.
      However, manual palpation was time-consuming and unreliable even if performed by
      expert clinicians. Therefore, automated accurate pulse detection with minimal
      interruptions of chest compression is highly desirable during cardiac arrest
      especially in out-of-hospital settings. OBJECTIVE: To investigate whether the
      acceleration (ACC) signals acquired from accelerometer-based CPR feedback sensor
      can be used to distinguish perfusing rhythm (PR) from pulseless electrical
      activity (PEA) in a porcine model of cardiac arrest. METHODS: Cardiac arrest was
      induced in 49 male adult pigs. ECG, arterial blood pressure (ABP) and ACC
      waveforms were simultaneously recorded during CPR. 3-second segments containing
      compression-free signals during chest compression pauses were extracted and only
      those segments with organized rhythm were used for analysis. PR was defined as
      systolic arterial pressure >60 mmHg and pulse pressure >10 mmHg, while PEA was
      defined as an organized rhythm that does not meet the above criteria for PR. Peak
      correlation coefficient (CCp) of the cross-correlation function between pre
      processed ECG and ACC, was used to discriminate PR and PEA. RESULTS: 63 PR and
      153 PEA were identified from the total of 1025 extracted segments. CCp was
      significantly higher for PR as compared to PEA (0.440+/-0.176 vs. 0.067+/-0.042,
      p<0.01) and highly correlated with ABP (r = 0.848, p<0.001). The area under the
      receiver operating characteristic curve, sensitivity, specificity and accuracy
      were 0.965, 93.6%, 97.5% and 96.7% for the ACC-based automatic spontaneous pulse
      detection. CONCLUSIONS: In this animal model, the ACC signals acquired from an
      accelerometer-based CPR feedback sensor can be used to detect the presence of
      spontaneous pulse with high accuracy.

PMID- 29220415
TI  - Effect of 3D microstructure of dermal papillae on SED concentration at a
      mechanoreceptor location.
AB  - The feeling of touch is an essential human sensation. Four types of
      mechanoreceptors (i.e., FA-I, SA-I, FA-II, and SA-II) in human skin signalize
      physical properties, such as shape, size, and texture, of an object that is
      touched and transmit the signal to the brain. Previous studies attempted to
      investigate the mechanical properties of skin microstructure and their effect on
      mechanoreceptors by using finite element modeling. However, very few studies have
      focused on the three-dimensional microstructure of dermal papillae, and this is
      related to that of FA-I receptors. A gap exists between conventional 2D models of
      dermal papillae and the natural configuration, which corresponds to a complex and
      uneven structure with depth. In this study, the three-dimensional microstructure
      of dermal papillae is modeled, and the differences between two-dimensional and
      three-dimensional aspects of dermal papillae on the strain energy density at
      receptor positions are examined. The three-dimensional microstructure has a
      focalizing effect and a localizing effect. Results also reveal the potential
      usefulness of these effects for tactile sensor design, and this may improve edge
      discrimination.

PMID- 29220417
TI  - A Major Win for the Treatment of Nail Psoriasis.
AB  - .

PMID- 29220416
TI  - The effectiveness and limitation of the national childhood hepatitis A
      vaccination program in the Republic of Korea: Findings from the Korean National
      Health and Nutrition Examination Survey (KNHANES), 2015.
AB  - BACKGROUND: Vaccination for hepatitis A virus (HAV) has been implemented as one
      of the national vaccination programs despite the epidemiological transition of
      HAV in the Republic of Korea. While the national HAV vaccination program is
      largely associated with the shift of socioeconomic trend in the country, concerns
      have been raised on the effectiveness of the HAV immunization. The objective of
      this study was to examine the epidemiological trend of HAV and assess the
      effectiveness of the nationwide HAV vaccination policy based on a nationally
      representative sample of the Korean population collected in 2015. METHODS: We
      analyzed anti-HAV of 5,856 respondents aged >=10 years collected from Korean
      National Health and Nutrition Examination Survey (KNHANES) data in 2015. We
      estimated age-adjusted anti-HAV prevalence by sociodemographic and other
      characteristics. We evaluated the factors associated with anti-HAV positivity
      among each age group (10-19, 20-29, 30-45 and over 45 years old). RESULTS: The
      prevalence of anti-HAV among adults aged >=10 years was 72.5% (95% confidence
      interval, CI, 73.7-71.4) in 2015. The lowest age-specific prevalence was among
      adults aged 20-29 years with 11.9% (95% CI 9.3-15.1%). The prevalence of anti-HAV
      among those aged 10-14 and 15-19 years was 59.7% (95% CI 52.7-66.4) and 24.0%
      (95% CI 19.5-29.3), respectively. The prevalence of anti-HAV among adults aged
      between 30 and 44 years rapidly increased from below 20% to above 90%. The
      prevalence of anti-HAV among adults aged >=45 years was 97.8% (95% CI 96.0-97.6).
      Factors significantly associated with anti-HAV positivity among those aged 10-19
      years old were young age, higher house income and high influenza vaccination
      rate. Compared to the respondents aged 10-19 years (those who were subject to the
      national childhood vaccine recommendation), those aged 20-29 years (those who
      were not subject to the recommendation) had low adjusted odds ratio (OR, 0.52 95%
      CI 0.34-.81 P-value = 0.004) for anti-HAV positivity. CONCLUSIONS: The age
      adjusted anti-HAV prevalence showed a U-shaped association, implying the high
      dependence of anti-HAV prevalence on age and the epidemiological shift. The
      inclusion of the hepatitis A vaccine into the national immunization
      recommendation was effective shown by the increase of immunity in the general
      population. However, the vaccination rate was low in the low-income group. Young
      adults aged 20-39 years may benefit from inclusion in the HAV vaccination program
      due to the significantly low vaccination rate.

PMID- 29220418
TI  - Plant-Mediated Female Transcriptomic Changes Post-Mating in a Tephritid Fruit
      Fly, Bactrocera tryoni.
AB  - Female post-mating behaviors are regulated by complex factors involving males,
      females, and the environment. In insects, plant secondary compounds that males
      actively forage for, may indirectly modify female behaviors by altering male
      behavior and physiology. In the tephritid fruit fly, Bactrocera tryoni, females
      mated with males previously fed on plant-derived phenylpropanoids (="lures" based
      on usage in tephritid literature), have longer mating refractoriness, greater
      fecundity, and reduced longevity than females mated with non-lure fed males. This
      system thus provides a model for studying transcriptional changes associated with
      those post-mating behaviors, as the genes regulating the phenotypic changes are
      likely to be expressed at a greater magnitude than in control females. We
      performed comparative transcriptome analyses using virgin B. tryoni females,
      females mated with control males (control-mated), and females mated with lure-fed
      males (lure-mated). We found 331 differentially expressed genes (DEGs) in control
      mated females and 80 additional DEGs in lure-mated females. Although DEGs in
      control-mated females are mostly immune response genes and chorion proteins, as
      reported in Drosophila species, DEGs in lure-mated females are titin-like muscle
      proteins, histones, sperm, and testis expressed proteins which have not been
      previously reported. While transcripts regulating mating (e.g., lingerer) did not
      show differential expression in either of the mated female classes, the odorant
      binding protein Obp56a was down-regulated. The exclusively enriched or suppressed
      genes in lure-mated females, novel transcripts such as titin and histones, and
      several taxa-specific transcripts reported here can shed more light on post
      mating transcriptional changes, and this can help understand factors possibly
      regulating female post-mating behaviors.

PMID- 29220419
TI  - High-Resolution Single-Cell Sequencing of Malaria Parasites.
AB  - Single-cell genomics is a powerful tool for determining the genetic architecture
      of complex communities of unicellular organisms. In areas of high transmission,
      malaria patients are often challenged by the activities of multiple Plasmodium
      falciparum lineages, which can potentiate pathology, spread drug resistance loci,
      and also complicate most genetic analysis. Single-cell sequencing of P.
      falciparum would be key to understanding infection complexity, though efforts are
      hampered by the extreme nucleotide composition of its genome (~80% AT-rich). To
      counter the low coverage achieved in previous studies, we targeted DNA-rich late
      stage parasites by Fluorescence-Activated Cell Sorting and whole genome
      sequencing. Our method routinely generates accurate, near-complete capture of the
      23 Mb P. falciparum genome (mean breadth of coverage 90.7%) at high efficiency.
      Data from 48 single-cell genomes derived from a polyclonal infection sampled in
      Chikhwawa, Malawi allowed for unambiguous determination of haplotype diversity
      and recent meiotic events, information that will aid public health efforts.

PMID- 29220420
TI  - Fear of Falling Predicts Incidence of Functional Disability 2 Years Later: A
      Perspective From an International Cohort Study.
AB  - Objective: To study the extent to which fear of falling (FOF) is associated with
      the onset of functional disability over a 2-year period in older adults using
      self-reported and performance-based measures. Methods: In 2012, 1,601
      participants (aged 65-74 years) were recruited from four sites: Kingston and
      Saint-Hyacinthe, Canada; Manizales, Colombia; and Natal, Brazil. They were re
      assessed in 2014. We quantified FOF using the Fall Efficacy Scale-International
      (FES-I; range: 16-64). Functional disability measures were (i) self-reported
      incident mobility disability, defined as difficulty climbing a flight of stairs
      or walking 400 m and (ii) incident poor physical performance, defined as a score
      <9 on the Short Physical Performance Battery. In the Poisson regression analysis,
      we included only those participants without functional disability at baseline to
      calculate incident risk ratios in 2014. Results: 1,355 participants completed the
      2014 assessment, of which 917 and 1,078 had no mobility disability and poor
      physical performance at baseline, respectively. In 2014, 131 (14.3%), and 166
      (15.4%) participants reported incident mobility disability and poor physical
      performance, respectively. After adjusting for age, sex, socioeconomic, and
      health covariates, a one-point increase in FES-I at baseline was significantly
      associated with a 4% increase in the risk of reporting incident mobility
      disability (95% CI: 1.02-1.05) and a 3% increase in the risk of developing poor
      physical performance at follow up in the overall sample (95%CI: 1.01-1.05).
      Conclusions: FOF is associated with a higher risk of incident mobility disability
      and poor physical performance in a cohort of older adults. It is increasingly
      important to study FOF's effect on functional disability and to take necessary
      measures to prevent the transition to end-stage disability.

PMID- 29220421
TI  - Optimal dose of dabigatran for the prevention of thromboembolism with minimal
      bleeding risk in Korean patients with atrial fibrillation.
AB  - Aims: We aim to determine the optimal dose of dabigatran in Korean patients with
      atrial fibrillation (AF). Methods and results: We analysed 1834 patients with non
      valvular AF, classified into a warfarin group (n = 990), dabigatran 150 mg group
      (D150, n = 294), and 110 mg group (D110, n = 550). The D110 group was further
      classified into patients concordant (co-D110, n = 367) and patients discordant
      (di-D110, n = 183) with guidelines to dose reduction. Propensity-matched 1-year
      clinical outcomes were then compared. Efficacy outcomes were defined as
      thromboembolism composed of new-onset stroke or systemic embolism. Safety
      outcomes were major bleeding. Both D150 and D110 had comparable efficacies as
      warfarin. However, only D110 significantly lowered the risk of major bleeding
      [hazard ratio (HR) 0.19, 95% confidence interval (CI) 0.07-0.55, P = 0.002]. In a
      subgroup analysis according to guideline-concordant indications for dose
      reduction, both co-D110 and di-D110 displayed a comparable efficacy as warfarin.
      Both co-D110 (HR 0.22, 95% CI 0.06-0.76, P = 0.017) and di-D110 (HR 0.11, 95% CI
      0.02-0.81, P = 0.030) significantly lowered incidences of major bleeding. There
      were no differences in the efficacy and safety between di-D110 and D150, and net
      clinical outcomes were similar. Conclusion: Although D150 and D110 had a
      comparable efficacy, only D110 lowered the risk of major bleeding in Korean AF
      patients compared with warfarin. Even the guideline-discordant use of dabigatran
      110 mg demonstrated a similar efficacy and safety compared with D150. However,
      further prospective randomized trials are needed in order to comprehensively
      evaluate whether D150 or D110 is the optimal dosage in Asian patients with AF.

PMID- 29220422
TI  - Atrioventricular node ablation and His bundle pacing.
AB  - Aims: Atrioventricular node ablation (AVNA) and right ventricular pacing (RVP)
      are effective therapies for patients with atrial fibrillation (AF) and rapid
      ventricular rates. His bundle pacing (HBP) is a physiologic alternative to RVP.
      The aim of our study is to assess the feasibility and safety of HBP in patients
      undergoing AVNA and its effect on left ventricular (LV) function. Methods and
      results: Permanent HBP is the preferred form of ventricular pacing at our
      institute. Atrioventricular node ablation and HBP were performed in patients with
      AF and difficulty in rate control. His bundle pacing implant characteristics and
      thresholds were recorded. Fluoroscopic relationship of AVNA site to HBP lead
      electrodes was documented. Left ventricular ejection fraction (LVEF) and New York
      Heart Association (NYHA) functional class at baseline and during follow-up were
      assessed. Forty-two patients underwent HBP and AVNA: age 74 +/- 11 years; men
      45%; HTN 64%; DM 19%; CAD 36%; permanent AF 40%; cardiomyopathy 55%. His bundle
      pacing was successful in 40 of 42 patients (95%). Successful AVNA site was at or
      below the ring electrode in 22 (no acute change in HBP threshold); above the ring
      electrode in 13 and left side in 2 pts (acute increase in HBP threshold in 7 of
      15 pts). Final HBP threshold at implant was 1 +/- 0.8 V@1 ms and increased to 1.6
      +/- 1.2 V@1 ms during a mean follow-up of 19 +/- 14 months. Left ventricular
      ejection fraction increased from 43 +/- 13% to 50 +/- 11% (P = 0.01). New York
      Heart Association functional status improved from 2.5 +/- 0.5 to 1.9 +/- 0.5 (P =
      0.04). Conclusion: Atrioventricular node ablation and HBP were successful in 95%
      of patients. His bundle pacing lead characteristics remained relatively stable.
      Left ventricular ejection fraction improved significantly during follow-up. His
      bundle pacing is feasible, safe and effective in pts undergoing AVNA.

PMID- 29220423
TI  - Tpeak-Tend interval during therapeutic hypothermia can predict upcoming
      ventricular fibrillation in subjects with aborted arrhythmic sudden cardiac
      death: 3-years follow-up results.
AB  - Aims: Prolonged Tpeak-Tend interval has been shown to be markers of
      arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of
      the obstacles to predict fatal ventricular arrhythmia. This study investigated
      whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated
      with ventricular fibrillation (VF) inducibility and clinical arrhythmia in
      subjects with aborted arrhythmic sudden cardiac death (SCD). Methods and results:
      The study group included 31 patients (24 males, age 39.1 +/- 17.6 years)
      presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude
      were measured in electrocardiogram (ECG) of the earliest medical contact and
      during TH; these patients underwent programmed ventricular stimulation. The
      summation of J-wave amplitude and QTc interval increased during TH. However, it
      was not associated with VF inducibility. Patients with inducible VF showed a
      small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 +/- 24.7
      vs. 94.0 +/- 55.6 ms, P = 0.044) and a marked increase of the dispersion during
      the TH (36.2 +/- 51.2 vs. -6.1 +/- 45.5 ms, P = 0.039). Twenty-four patients
      underwent implantable cardioverter defibrillator (ICD) implantation. Among them,
      the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH
      developed VF more frequently (QTc, 511.9 +/- 53.71 ms vs. 566.5 +/- 56.08 ms, P =
      0.038; Tpeak-Tend interval, 145.6 +/- 38.4 ms vs. 185.7 +/- 49.95 ms, P = 0.048;
      precordial Tpeak-Tend interval, 139.3 +/- 35.11 ms vs. 185.7 +/- 49.95 ms, P =
      0.018). The initial VF inducibility was not related with the VF development in
      follow-up. Conclusion: In patients with aborted arrhythmic SCD, long Tpeak-Tend
      interval and QTc interval during TH could predict VF development in their follow
      up.

PMID- 29220424
TI  - Genetically deprived vitamin D exposure predisposes to atrial fibrillation.
AB  - Aims: Low vitamin D level is associated with atrial fibrillation (AF) and may be
      implicated in its pathogenesis. Methods and results: We studied single nucleotide
      polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25
      hydroxyvitamin D [25(OH)D] levels in an age- and gender-matched case-control
      study (controls without AF: mean age 68.6 +/- 8.7 years, female 25%; n = 1019;
      with AF: mean age 69.7 +/- 9.5 years, female 30%; n = 156) recruited from a
      Chinese clinical cohort of patients with stable coronary artery disease. Twelve
      SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic:
      rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116;
      vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041,
      rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic
      risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH)D as
      a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC
      were significantly associated with serum 25(OH)D (rs4588, P < 0.001; rs2282679, P
      < 0.001; rs7041, P = 0.011; rs1155563, P < 0.001; all other SNPs, P > 0.05).
      Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently
      predictive of serum 25(OH)D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P
      < 0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3)
      independently predicted an increased risk of AF, compared to a high GRS (4-8)
      (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). Conclusion: Genetically
      deprived vitamin D exposure predisposes to increased AF among patients with
      coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative
      mechanisms warrants further studies.

PMID- 29220425
TI  - A leaflet plication clip is an effective surgical template for mitral valve
      foldoplasty.
AB  - OBJECTIVES: During mitral valve repair using the foldoplasty technique, correct
      judgement of the necessary dimensions and orientation of the leaflet fold is a
      critical but challenging step that can affect the chances of successful repair.
      In this study, we investigated whether a leaflet plication clip can be used to
      guide suture foldoplasty for posterior leaflet prolapse of the mitral valve.
      METHODS: Complete posterior leaflet prolapse was created in both in vivo and ex
      vivo pig hearts by severing the chordae supporting the middle scallop. A
      plication clip was applied to perform leaflet foldoplasty. Sutures were then
      placed using the clip as a template and the clip was removed. Leaflet width after
      flail creation, clip application and suture placement was determined in an ex
      vivo test. In vivo repair and evaluation was then performed in 7 pigs to
      determine the repair efficacy under normal physiological loading, at 1 and 6 h
      after recovery from cardiopulmonary bypass. RESULTS: Leaflet width after suture
      placement was comparable to the clip alone (7.0 +/- 1.4 vs 9.0 +/- 1.6) and both
      were significantly less than the flail width 15.7+/- 2.5 mm. In vivo, average
      coaptation height following repair was restored to 4.7 +/- 1.4 mm and 4.2 +/- 1.3
      mm at 1 and 6 h, respectively, after recovery compared with the baseline height
      of 5.5 +/- 0.9 mm. Mitral regurgitation was reduced from moderate-severe to mild
      or less, and addition of a De-Vega annuloplasty in the last 3 animals abolished
      residual leaks to trivial or none. CONCLUSIONS: Application of the adjustable
      leaflet plication clip facilitated accurate determination of the correct
      position, width, height and orientation of the foldoplasty. Any necessary clip
      repositioning was made prior to the placement of sutures avoiding the need to
      redo the sutures. This approach could potentially help improve the ease and
      reproducibility of the foldoplasty repair.

PMID- 29220428
TI  - Sexual Dysfunction in Patients With Inflammatory Bowel Disease is not just a
      Matter of Quality of Life.

PMID- 29220427
TI  - Steroid but not Biological Therapy Elevates the risk of Venous Thromboembolic
      Events in Inflammatory Bowel Disease: A Meta-Analysis.
AB  - Background and Aims: Inflammatory bowel disease [IBD] is associated with a 1.5-
      to 3-fold increased risk of venous thromboembolism [VTE] events. The aim of this
      study was to determine the risk of VTE in IBD as a complication of systemic
      corticosteroids and anti-tumour necrosis factor alpha [TNFalpha] therapies.
      Methods: A systematic review and meta-analysis was conducted, which conforms to
      the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA]
      statement. PubMed, EMBASE, Cochrane Library and Web of Science were searched for
      English-language studies published from inception inclusive of 15 April 2017. The
      population-intervention-comparison-outcome [PICO] format and statistically the
      random-effects and fixed-effect models were used to compare VTE risk during
      steroid and anti-TNFalpha treatment. Quality of the included studies was assessed
      using the Newcastle-Ottawa scale. The PROSPERO registration number is
      42017070084. Results: We identified 817 records, of which eight observational
      studies, involving 58518 IBD patients, were eligible for quantitative synthesis.
      In total, 3260 thromboembolic events occurred. Systemic corticosteroids were
      associated with a significantly higher rate of VTE complication in IBD patients
      as compared to IBD patients without steroid medication (odds ratio [OR]: 2.202;
      95% confidence interval [CI]: 1.698-2.856, p < 0.001). In contrast, treatment
      with anti-TNFalpha agents resulted in a 5-fold decreased risk of VTE compared to
      steroid medication [OR: 0.267; 95% CI: 0.106-0.674, p = 0.005]. Conclusion: VTE
      risk should be carefully assessed and considered when deciding between anti
      TNFalpha and steroids in the management of severe flare-ups. Thromboprophylaxis
      guidelines should be followed, no matter the therapy choice.

PMID- 29220426
TI  - Isl1beta Overexpression With Key beta Cell Transcription Factors Enhances Glucose
      Responsive Hepatic Insulin Production and Secretion.
AB  - Adenoviral gene transfer of key beta cell developmental regulators including
      Pdx1, Neurod1, and Mafa (PDA) has been reported to generate insulin-producing
      cells in the liver. However, PDA insulin secretion is transient and glucose
      unresponsive. Here, we report that an additional beta cell developmental
      regulator, insulin gene enhancer binding protein splicing variant (Isl1beta),
      improved insulin production and glucose-responsive secretion in PDA mice.
      Microarray gene expression analysis suggested that adenoviral PDA transfer
      required an additional element for mature beta cell generation, such as Isl1 and
      Elf3 in the liver. In vitro promoter analysis indicated that splicing variant
      Isl1, or Isl1beta, is an important factor for transcriptional activity of the
      insulin gene. In vivo bioluminescence monitoring using insulin promoter
      luciferase transgenic mice verified that adenoviral PDA + Isl1beta transfer
      produced highly intense luminescence from the liver, which peaked at day 7 and
      persisted for more than 10 days. Using insulin promoter-GFP transgenic mice, we
      further confirmed that Isl1beta supplementation to PDA augmented insulin
      producing cells in the liver, insulin production and secretion, and beta cell
      related genes. Finally, the PDA + Isl1beta combination ameliorated hyperglycemia
      in diabetic mice for 28 days and enhanced glucose tolerance and responsiveness.
      Thus, our results suggest that Isl1beta is a key additional transcriptional
      factor for advancing the generation of insulin-producing cells in the liver in
      combination with PDA.

PMID- 29220429
TI  - Combination Therapy With Adalimumab and Thiopurines in Inflammatory Bowel
      Disease: Is It a Case of Nepotism in Pharmacology?

PMID- 29220430
TI  - Postoperative Outcomes in Ustekinumab-Treated Patients Undergoing Abdominal
      Operations for Crohn's Disease.
AB  - Background: Ustekinumab, a monoclonal antibody targeting interleukins-12 and -23
      is used to treat adults with Crohn's disease [CD]. We determined the 30-day
      postoperative infectious complication rate among CD patients who received
      ustekinumab within the 12 weeks prior to an abdominal operation as compared with
      patients who received anti-tumor necrosis factor [TNF] agents. Methods: A
      retrospective chart review of adults with CD who underwent an abdominal operation
      between January 1, 2015 and May 1, 2017 was performed across six sites. Surgical
      site infection [SSI] was defined as superficial skin and soft tissue infection,
      intra-abdominal abscess, anastomotic leak, and mucocutaneous separation of the
      stoma. Results: Forty-four patients received ustekinumab and 169 patients
      received anti-TNF therapy within the 12 weeks prior to surgery. The two groups
      were similar, except anti-TNF patients were more likely to have received
      combination therapy with an immunomodulator [P = 0.006]. There were no
      significant differences in postoperative SSI [13% in ustekinumab versus 20% in
      anti TNF-treated patients, p = 0.61] or hospital readmission rates [18% versus
      10%, respectively, p = 0.14], but ustekinumab-treated patients had a higher rate
      of return to the operating room [16% versus 5%; P = 0.01]. There were no
      significant predictors identified on multivariable analysis. Conclusions: Of the
      44 patients with CD who received ustekinumab within the 12 weeks prior to a major
      abdominal operation, 13% experienced a 30-day postoperative SSI, not
      statistically different from the 20% found in the anti-TNF cohort. Ustekinumab
      treatment within 12 weeks of surgery does not appear to increase the risk of
      postoperative SSI above that of CD patients treated with anti-TNF medications.

PMID- 29220431
TI  - In silico characterization of tandem repeats in Trichophyton rubrum and related
      dermatophytes provides new insights into their role in pathogenesis.
AB  - Database URL: http://comp.mch.ifsuldeminas.edu.br/dtrdb/.

PMID- 29220432
TI  - Triage by ranking to support the curation of protein interactions.
AB  - Database URL: http://candy.hesge.ch/nextA5.

PMID- 29220433
TI  - TIBLE: a web-based, freely accessible resource for small-molecule binding data
      for mycobacterial species.
AB  - Database URL: http://www-cryst.bioc.cam.ac.uk/tible/.

PMID- 29220434
TI  - decodeRNA- predicting non-coding RNA functions using guilt-by-association.
AB  - Database URL: http://www.decoderna.org.

PMID- 29220436
TI  - NutriChem 2.0: exploring the effect of plant-based foods on human health and drug
      efficacy.
AB  - Database URL: http://sbb.hku.hk/services/NutriChem-2.0/.

PMID- 29220435
TI  - MGIS: managing banana (Musa spp.) genetic resources information and high
      throughput genotyping data.
AB  - Database URL: https://www.crop-diversity.org/mgis/.

PMID- 29220437
TI  - LeishDB: a database of coding gene annotation and non-coding RNAs in Leishmania
      braziliensis.
AB  - Database URL: www.leishdb.com.

PMID- 29220438
TI  - PigVar: a database of pig variations and positive selection signatures.
AB  - Database URL: http://www.ibiomedical.net/pigvar/.

PMID- 29220439
TI  - Text mining and expert curation to develop a database on psychiatric diseases and
      their genes.
AB  - Database URL: http://www.psygenet.org. PsyGeNET corpus:
      http://www.psygenet.org/ds/PsyGeNET/results/psygenetCorpus.tar.

PMID- 29220440
TI  - MGFD: the maize gene families database.

PMID- 29220442
TI  - Benchmarking distributed data warehouse solutions for storing genomic variant
      information.
AB  - Database URL: https://github.com/ZSI-Bio/variantsdwh.

PMID- 29220443
TI  - RetrogeneDB-a database of plant and animal retrocopies.
AB  - Database URL: http://yeti.amu.edu.pl/retrogenedb. Secondary database URL:
      http://rhesus.amu.edu.pl/retrogenedb.

PMID- 29220441
TI  - Improved annotation of the insect vector of citrus greening disease: biocuration
      by a diverse genomics community.
AB  - Database URL: https://citrusgreening.org/.

PMID- 29220445
TI  - The Grass Carp Genome Database (GCGD): an online platform for genome features and
      annotations.
AB  - Database URL: http://bioinfo.ihb.ac.cn/gcgd.

PMID- 29220444
TI  - NRDTD: a database for clinically or experimentally supported non-coding RNAs and
      drug targets associations.
AB  - Database URL: http://chengroup.cumt.edu.cn/NRDTD.

PMID- 29220446
TI  - New extension software modules to enhance searching and display of transcriptome
      data in Tripal databases.
AB  - Database URL Tripal Elasticsearch module:
      https://github.com/tripal/tripal_elasticsearch. Tripal Analysis Expression
      module: https://github.com/tripal/tripal_analysis_expression.

PMID- 29220447
TI  - MiRIAD update: using alternative polyadenylation, protein interaction network
      analysis and additional species to enhance exploration of the role of intragenic
      miRNAs and their host genes.
AB  - Database URL: http://www.miriad-database.org.

PMID- 29220448
TI  - Cancer Odor Database (COD): a critical databank for cancer diagnosis research.
AB  - Database URL: http://bioinf.modares.ac.ir/software/cod/.

PMID- 29220449
TI  - RegulatorDB: a resource for the analysis of yeast transcriptional regulation.
AB  - Database URL: http://wyrickbioinfo2.smb.wsu.edu/RegulatorDB.

PMID- 29220450
TI  - CTD2 Dashboard: a searchable web interface to connect validated results from the
      Cancer Target Discovery and Development Network.
AB  - Database URL: https://ctd2-dashboard.nci.nih.gov/.

PMID- 29220451
TI  - BioSearch: a semantic search engine for Bio2RDF.
AB  - Database URL: http://ws.nju.edu.cn/biosearch/.

PMID- 29220452
TI  - A RESTful application programming interface for the PubMLST molecular typing and
      genome databases.
AB  - Database URL: http://rest.pubmlst.org/.

PMID- 29220453
TI  - A publicly available benchmark for biomedical dataset retrieval: the reference
      standard for the 2016 bioCADDIE dataset retrieval challenge.
AB  - Database URL: https://biocaddie.org/benchmark-data.

PMID- 29220454
TI  - Elsevier's approach to the bioCADDIE 2016 Dataset Retrieval Challenge.
AB  - Database URL: https://data.mendeley.com/datasets/zd9dxpyybg/1.

PMID- 29220455
TI  - Impact of translation on named-entity recognition in radiology texts.
AB  - Database URL: https://github.com/lasigeBioTM/MRRAD.

PMID- 29220456
TI  - RampDB: a web application and database for the exploration and prediction of
      receptor activity modifying protein interactions.
AB  - Database URL: http://rampdb.biology.gatech.edu.

PMID- 29220457
TI  - Multi-field query expansion is effective for biomedical dataset retrieval.
AB  - In the context of the bioCADDIE challenge addressing information retrieval of
      biomedical datasets, we propose a method for retrieval of biomedical data sets
      with heterogenous schemas through query reformulation. In particular, the method
      proposed transforms the initial query into a multi-field query that is then
      enriched with terms that are likely to occur in the relevant datasets. We compare
      and evaluate two query expansion strategies, one based on the Rocchio method and
      another based on a biomedical lexicon. We then perform a comprehensive
      comparative evaluation of our method on the bioCADDIE dataset collection for
      biomedical retrieval. We demonstrate the effectiveness of our multi-field query
      method compared to two baselines, with MAP improved from 0.2171 and 0.2669 to
      0.2996. We also show the benefits of query expansion, where the Rocchio
      expanstion method improves the MAP for our two baselines from 0.2171 and 0.2669
      to 0.335. We show that the Rocchio query expansion method slightly outperforms
      the one based on the biomedical lexicon as a source of terms, with an improvement
      of roughly 3% for MAP. However, the query expansion method based on the
      biomedical lexicon is much less resource intensive since it does not require
      computation of any relevance feedback set or any initial execution of the query.
      Hence, in term of trade-off between efficiency, execution time and retrieval
      accuracy, we argue that the query expansion method based on the biomedical
      lexicon offers the best performance for a prototype biomedical data search engine
      intended to be used at a large scale. In the official bioCADDIE challenge
      results, although our approach is ranked seventh in terms of the infNDCG
      evaluation metric, it ranks second in term of P@10 and NDCG. Hence, the method
      proposed here provides overall good retrieval performance in relation to the
      approaches of other competitors. Consequently, the observations made in this
      paper should benefit the development of a Data Discovery Index prototype or the
      improvement of the existing one.

PMID- 29220458
TI  - AllerBase: a comprehensive allergen knowledgebase.
AB  - Database URL: http://bioinfo.net.in/AllerBase/Home.html.

PMID- 29220459
TI  - IsoPlot: a database for comparison of mRNA isoforms in fruit fly and mosquitoes.
AB  - Database URL: http://isoplot.iis.sinica.edu.tw/.

PMID- 29220460
TI  - Echinobase: an expanding resource for echinoderm genomic information.
AB  - Database URL: http://www.echinobase.org.

PMID- 29220461
TI  - SFMetaDB: a comprehensive annotation of mouse RNA splicing factor RNA-Seq
      datasets.
AB  - Although the number of RNA-Seq datasets deposited publicly has increased over the
      past few years, incomplete annotation of the associated metadata limits their
      potential use. Because of the importance of RNA splicing in diseases and
      biological processes, we constructed a database called SFMetaDB by curating
      datasets related with RNA splicing factors. Our effort focused on the RNA-Seq
      datasets in which splicing factors were knocked-down, knocked-out or over
      expressed, leading to 75 datasets corresponding to 56 splicing factors. These
      datasets can be used in differential alternative splicing analysis for the
      identification of the potential targets of these splicing factors and other
      functional studies. Surprisingly, only ~15% of all the splicing factors have been
      studied by loss- or gain-of-function experiments using RNA-Seq. In particular,
      splicing factors with domains from a few dominant Pfam domain families have not
      been studied. This suggests a significant gap that needs to be addressed to fully
      elucidate the splicing regulatory landscape. Indeed, there are already mouse
      models available for ~20 of the unstudied splicing factors, and it can be a
      fruitful research direction to study these splicing factors in vitro and in vivo
      using RNA-Seq.Database URL:http://sfmetadb.ece.tamu.edu/

PMID- 29220462
TI  - First steps in automatic summarization of transcription factor properties for
      RegulonDB: classification of sentences about structural domains and regulated
      processes.
AB  - Database URL: RegulonDB, http://regulondb.ccg.unam.mx.

PMID- 29220463
TI  - An online analytical processing multi-dimensional data warehouse for malaria
      data.
AB  - Database URL: https://dw.vecnet.org/datawarehouse/.

PMID- 29220464
TI  - KiPho: malaria parasite kinome and phosphatome portal.
AB  - The Plasmodium kinases and phosphatases play an essential role in the regulation
      of substrate reversible-phosphorylation and overall cellular homeostasis.
      Reversible phosphorylation is one of the key post-translational modifications
      (PTMs) essential for parasite survival. Thus, a complete and comprehensive
      information of malarial kinases and phosphatases as a single web resource will
      not only aid in systematic and better understanding of the PTMs, but also
      facilitate efforts to look for novel drug targets for malaria. In the current
      work, we have developed KiPho, a comprehensive and one step web-based information
      resource for Plasmodium kinases and phosphatases. To develop KiPho, we have made
      use of search methods to retrieve, consolidate and integrate predicted as well as
      annotated information from several publically available web repositories.
      Additionally, we have incorporated relevant and manually curated data, which will
      be updated from time to time with the availability of new information. The KiPho
      (Malaria Parasite Kinome-Phosphatome) resource is freely available at
      http://bioinfo.icgeb.res.in/kipho.

PMID- 29220465
TI  - In-Cardiome: integrated knowledgebase for coronary artery disease enabling
      translational research.
AB  - Database URL: www.tri-incardiome.org.

PMID- 29220466
TI  - Improving taxonomic accuracy for fungi in public sequence databases: applying
      'one name one species' in well-defined genera with Trichoderma/Hypocrea as a test
      case.
AB  - Database URL: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353.

PMID- 29220467
TI  - Query expansion using MeSH terms for dataset retrieval: OHSU at the bioCADDIE
      2016 dataset retrieval challenge.
AB  - Database URL: https://biocaddie.org/benchmark-data.

PMID- 29220469
TI  - Edaphostat: interactive ecological analysis of soil organism occurrences and
      preferences from the Edaphobase data warehouse.
AB  - Database URL: Edaphostat is part of the Edaphobase Web Application available at
      https://portal.edaphobase.org.

PMID- 29220468
TI  - EUCANEXT: an integrated database for the exploration of genomic and
      transcriptomic data from Eucalyptus species.
AB  - Database URL: http://www.lge.ibi.unicamp.br/eucalyptusdb.

PMID- 29220470
TI  - DLREFD: a database providing associations of long non-coding RNAs, environmental
      factors and phenotypes.
AB  - Database URL: http://chengroup.cumt.edu.cn/DLREFD.

PMID- 29220471
TI  - FishTrace: a genetic catalogue of European fishes.
AB  - Database URL: https://fishtrace.jrc.ec.europa.eu.

PMID- 29220472
TI  - Proficiency of data interpretation: identification of signaling SNPs/specific
      loci for coronary artery disease.
AB  - Database URLs:
      http://www.regulomedb.org/;https://www.broadinstitute.org/mpg/snap/.

PMID- 29220473
TI  - YGMD: a repository for yeast cooperative transcription factor sets and their
      target gene modules.
AB  - Database URL: http://cosbi4.ee.ncku.edu.tw/YGMD/ ,
      http://cosbi5.ee.ncku.edu.tw/YGMD/ or http://cosbi.ee.ncku.edu.tw/YGMD/.

PMID- 29220474
TI  - Database of resistance related metabolites in Wheat Fusarium head blight Disease
      (MWFD).
AB  - Database URL: https://bioinfo.nrc.ca/mwfd/index.php.

PMID- 29220475
TI  - Improving average ranking precision in user searches for biomedical research
      datasets.
AB  - Database URL: https://biocaddie.org/benchmark-data.

PMID- 29220476
TI  - eGenPub, a text mining system for extending computationally mapped bibliography
      for UniProt Knowledgebase by capturing centrality.
AB  - UniProt Knowledgebase (UniProtKB) is a publicly available database with access to
      a vast amount of protein sequence and functional information. To widen the scope
      of the publications associated with a protein entry, UniProt has introduced the
      computationally mapped additional bibliography section, which includes literature
      collected from external sources. In this article, we describe a text mining
      system, eGenPub, which selects articles that are 'about' specific proteins and
      allows automatic identification of additional bibliography for given UniProt
      protein entries. Focusing on plant proteins initially, eGenPub utilizes a gene
      normalization tool called pGenN, and a trained support vector machine model,
      which achieves a precision of 95.3%, to predict whether an article, based on its
      abstract, should be linked to a given UniProt entry. We have conducted a full
      scale PubMed processing using eGenPub for eight common plant species. Altogether,
      9025 articles are identified as relevant bibliography for 4752 UniProt entries,
      among which 5252 are additional papers not in the existing publication section.
      These newly computationally mapped additional bibliography via eGenPub is being
      integrated in the UniProt production pipeline, and can be accessed via the
      UniProtKB protein entry publication view.

PMID- 29220477
TI  - Update notifications for the BioCyc collection of databases.
AB  - Database URL: https://BioCyc.org , https://EcoCyc.org , https://MetaCyc.org.

PMID- 29220478
TI  - A semantic-based workflow for biomedical literature annotation.
AB  - Computational annotation of textual information has taken on an important role in
      knowledge extraction from the biomedical literature, since most of the relevant
      information from scientific findings is still maintained in text format. In this
      endeavour, annotation tools can assist in the identification of biomedical
      concepts and their relationships, providing faster reading and curation
      processes, with reduced costs. However, the separate usage of distinct annotation
      systems results in highly heterogeneous data, as it is difficult to efficiently
      combine and exchange this valuable asset. Moreover, despite the existence of
      several annotation formats, there is no unified way to integrate miscellaneous
      annotation outcomes into a reusable, sharable and searchable structure. Taking up
      this challenge, we present a modular architecture for textual information
      integration using semantic web features and services. The solution described
      allows the migration of curation data into a common model, providing a suitable
      transition process in which multiple annotation data can be integrated and
      enriched, with the possibility of being shared, compared and reused across
      semantic knowledge bases.

PMID- 29220479
TI  - Collaborative relation annotation and quality analysis in Markyt environment.
AB  - Database URL: http://markyt.org.

PMID- 29220480
TI  - 'Working away in that Grey Area...' A qualitative exploration of the challenges
      general practitioners experience when managing behavioural and psychological
      symptoms of dementia.
AB  - Background: general practitioners (GPs) have identified the management of
      behavioural and psychological symptoms of dementia (BPSD) as a particularly
      challenging aspect of dementia care. However, there is a paucity of research on
      why GPs find BPSD challenging and how this influences the care they offer to
      their patients with dementia. Objectives: to establish the challenges GPs
      experience when managing BPSD; to explore how these challenges influence GPs'
      management decisions; and to identify strategies for overcoming these challenges.
      Design: qualitative study of GPs experiences of managing BPSD. Methods: semi
      structured interviews were conducted with 16 GPs in the Republic of Ireland. GPs
      were purposively recruited to include participants with differing levels of
      experience caring for people with BPSD in nursing homes and in community settings
      to provide maximum diversity of views. Interviews were analysed thematically.
      Results: three main challenges of managing BPSD were identified; lack of clinical
      guidance, stretched resources and difficulties managing expectations. The lack of
      relevant clinical guidance available affected GPs' confidence when managing BPSD.
      In the absence of appropriate resources GPs felt reliant upon sedative
      medications. GPs believed their advocacy role was further compromised by the
      difficulties they experienced managing expectations of family caregivers and
      nursing home staff. Conclusions: this study helps to explain the apparent
      discrepancy between best practice recommendations in BPSD and real-life practice.
      It will be used to inform the design of an intervention to support the management
      of BPSD in general practice.

PMID- 29220482
TI  - The climate of neurofeedback: scientific rigour and the perils of ideology.

PMID- 29220481
TI  - Blended Refuge and Insect Resistance Management for Insecticidal Corn.
AB  - In this review, we evaluate the intentional mixing or blending of insecticidal
      seed with refuge seed for managing resistance by insects to insecticidal corn
      (Zea mays). We first describe the pest biology and farming practices that will
      contribute to weighing trade-offs between using block refuges and blended
      refuges. Case studies are presented to demonstrate how the trade-offs will differ
      in different systems. We compare biological aspects of several abstract models to
      guide the reader through the history of modeling, which has played a key role in
      the promotion or denigration of blending in various scientific debates about
      insect resistance management for insecticidal crops. We conclude that the use of
      blended refuge should be considered on a case-by-case basis after evaluation of
      insect biology, environment, and farmer behavior. For Diabrotica virgifera
      virgifera, Ostrinia nubilalis, and Helicoverpa zea in the United States, blended
      refuge provides similar, if not longer, delays in the evolution of resistance
      compared to separate block refuges.

PMID- 29220483
TI  - Prenatal Exposure to Bisphenol A Disrupts Naturally Occurring Bimodal DNA
      Methylation at Proximal Promoter of fggy, an Obesity-Relevant Gene Encoding a
      Carbohydrate Kinase, in Gonadal White Adipose Tissues of CD-1 Mice.
AB  - Exposure of mammalian fetuses to endocrine disruptors can increase the risk of
      adult-onset diseases. We previously showed that exposure of mouse fetuses to
      bisphenol A (BPA) caused adult-onset obesity. To examine roles of epigenetic
      changes in this delayed toxicity, we determined the effects of fetal mouse
      exposure to BPA on genome-wide DNA methylation and messenger RNA (mRNA)
      expression in gonadal white adipose tissues (WATs) by deep sequencing, bisulfite
      pyrosequencing, and real-time quantitative polymerase chain reaction. Pregnant CD
      1 mice (F0) were dosed daily with 0, 5, or 500 MUg/kg/d BPA during gestational
      days 9 to 18, and the weaned F1 animals were fed ad libitum with standard chow
      until they were euthanized at 19 weeks old. In the vehicle-exposed F1 animals,
      fggy promoter showed a clear bimodal pattern of very strong (55% to 95%) or very
      weak (5% to 30%) DNA methylation occurring at nearly equal incidence with no
      intermediate strength. Promoter hypermethylation completely suppressed mRNA
      expression. BPA exposure eliminated this naturally occurring dichotomy, shifting
      fggy promoter toward the hypomethylation state to release transcriptional
      suppression. The strength of Fggy mRNA expression significantly correlated with
      increased whole body weight and gonadal fat weight of males but not females.
      Bioinformatics studies showed that expression of Fggy mRNA is stronger in mouse
      WATs than in brown adipose tissues and enhanced in gonadal fat by diet-induced
      obesity. These observations suggest that prenatal exposure to BPA may disrupt the
      physiological bimodal nature of epigenetic regulation of fggy in mouse WATs,
      possibly contributing to the adult-onset obesity phenotype.

PMID- 29220484
TI  - Human Immunodeficiency Virus Infection And Hypertension. Is There a Connection?
AB  - Data support that hypertension (HTN) is prevalent among human immunodeficiency
      virus (HIV) patients contributing to increased risk of cardiovascular disease.
      Immunodeficiency and prolonged antiretroviral treatment along with common risk
      factors including older age, male gender, and high body mass index might conduce
      to greater incidence of HTN. The purpose of this review was to summarize recent
      evidence of the increased cardiovascular risk in these patents linking HIV
      infection to HTN.

PMID- 29220485
TI  - funRiceGenes dataset for comprehensive understanding and application of rice
      functional genes.
AB  - Background: As a main staple food, rice is also a model plant for functional
      genomic studies of monocots. Decoding of every DNA element of the rice genome is
      essential for genetic improvement to address increasing food demands. The past 15
      years have witnessed extraordinary advances in rice functional genomics.
      Systematic characterization and proper deposition of every rice gene are vital
      for both functional studies and crop genetic improvement. Findings: We built a
      comprehensive and accurate dataset of ~2800 functionally characterized rice genes
      and ~5000 members of different gene families by integrating data from available
      databases and reviewing every publication on rice functional genomic studies. The
      dataset accounts for 19.2% of the 39 045 annotated protein-coding rice genes,
      which provides the most exhaustive archive for investigating the functions of
      rice genes. We also constructed 214 gene interaction networks based on 1841
      connections between 1310 genes. The largest network with 762 genes indicated that
      pleiotropic genes linked different biological pathways. Increasing degree of
      conservation of the flowering pathway was observed among more closely related
      plants, implying substantial value of rice genes for future dissection of
      flowering regulation in other crops. All data are deposited in the funRiceGenes
      database (https://funricegenes.github.io/). Functionality for advanced search and
      continuous updating of the database are provided by a Shiny application
      (http://funricegenes.ncpgr.cn/). Conclusions: The funRiceGenes dataset would
      enable further exploring of the crosslink between gene functions and natural
      variations in rice, which can also facilitate breeding design to improve target
      agronomic traits of rice.

PMID- 29220487
TI  - Ancestral Genome Estimation Reveals the History of Ecological Diversification in
      Agrobacterium.
AB  - Horizontal gene transfer (HGT) is considered as a major source of innovation in
      bacteria, and as such is expected to drive adaptation to new ecological niches.
      However, among the many genes acquired through HGT along the diversification
      history of genomes, only a fraction may have actively contributed to sustained
      ecological adaptation. We used a phylogenetic approach accounting for the
      transfer of genes (or groups of genes) to estimate the history of genomes in
      Agrobacterium biovar 1, a diverse group of soil and plant-dwelling bacterial
      species. We identified clade-specific blocks of cotransferred genes encoding
      coherent biochemical pathways that may have contributed to the evolutionary
      success of key Agrobacterium clades. This pattern of gene coevolution rejects a
      neutral model of transfer, in which neighboring genes would be transferred
      independently of their function and rather suggests purifying selection on
      collectively coded acquired pathways. The acquisition of these synapomorphic
      blocks of cofunctioning genes probably drove the ecological diversification of
      Agrobacterium and defined features of ancestral ecological niches, which
      consistently hint at a strong selective role of host plant rhizospheres.

PMID- 29220488
TI  - Disentangling Immediate Adaptive Introgression from Selection on Standing
      Introgressed Variation in Humans.
AB  - Recent studies have reported evidence suggesting that portions of contemporary
      human genomes introgressed from archaic hominin populations went to high
      frequencies due to positive selection. However, no study to date has specifically
      addressed the post-introgression population dynamics of these putative cases of
      adaptive introgression. Here, for the first time, we specifically define cases of
      immediate adaptive introgression (iAI), in which archaic haplotypes rose to high
      frequencies in humans as a result of a selective sweep that occurred shortly
      after the introgression event. We define these cases as distinct from instances
      of selection on standing introgressed variation (SI), in which an introgressed
      haplotype initially segregated neutrally and subsequently underwent positive
      selection. Using a geographically diverse dataset, we report novel cases of
      selection on introgressed variation in living humans and shortlisted among these
      cases those whose selective sweeps are more consistent with having been the
      product of iAI rather than SI. Many of these novel inferred iAI haplotypes have
      potential biological relevance, including three introgressed haplotypes that
      contain immune-related genes in West Siberians, South Asians, and West Eurasians.
      Overall, our results suggest that iAI may not represent the full picture of
      positive selection on archaically introgressed haplotypes in humans and that more
      work needs to be done to analyze the role of SI in the archaic introgression
      landscape of living humans.

PMID- 29220486
TI  - Transcriptome Signatures of Selection, Drift, Introgression, and Gene Duplication
      in the Evolution of an Extremophile Endemic Plant.
AB  - Plants on serpentine soils provide extreme examples of adaptation to environment,
      and thus offer excellent models for the study of evolution at the molecular and
      genomic level. Serpentine outcrops are derived from ultramafic rock and have
      extremely low levels of essential plant nutrients (e.g., N, P, K, and Ca), as
      well as toxic levels of heavy metals (e.g., Ni, Cr, and Co) and low moisture
      availability. These outcrops provide habitat to a number of endemic plant
      species, including the annual mustard Caulanthus amplexicaulis var. barbarae
      (Cab) (Brassicaceae). Its sister taxon, C. amplexicaulis var. amplexicaulis
      (Caa), is intolerant to serpentine soils. Here, we assembled and annotated
      comprehensive reference transcriptomes of both Caa and Cab for use in protein
      coding sequence comparisons. A set of 29,443 reciprocal best Blast hit (RBH)
      orthologs between Caa and Cab was compared with identify coding sequence
      variants, revealing a high genome-wide dN/dS ratio between the two taxa (mean =
      0.346). We show that elevated dN/dS likely results from the composite effects of
      genetic drift, positive selection, and the relaxation of negative selection.
      Further, analysis of paralogs within each taxon revealed the signature of a
      period of elevated gene duplication (~10 Ma) that is shared with other species of
      the tribe Thelypodieae, and may have played a role in the striking morphological
      and ecological diversity of this tribe. In addition, distribution of the
      synonymous substitution rate, dS, is strongly bimodal, indicating a history of
      reticulate evolution that may have contributed to serpentine adaptation.

PMID- 29220489
TI  - Diversity of translation initiation mechanisms across bacterial species is driven
      by environmental conditions and growth demands.
AB  - The Shine-Dalgarno (SD) sequence motif is frequently found upstream of protein
      coding genes and is thought to be the dominant mechanism of translation
      initiation used by bacteria. Experimental studies have shown that the SD sequence
      facilitates start codon recognition and enhances translation initiation by
      directly interacting with the highly conserved anti-Shine-Dalgarno sequence on
      the 30S ribosomal subunit. However, the proportion of SD-led genes within a
      genome varies across species and the factors governing this variation in
      translation initiation mechanisms remain largely unknown. Here, we conduct a
      phylogenetically-informed analysis and find that species capable of rapid growth
      contain a higher proportion of SD-led genes throughout their genomes. We show
      that SD sequence utilization co-varies with a suite of genomic features that are
      important for efficient translation initiation and elongation. In addition to
      these endogenous genomic factors, we further show that exogenous environmental
      factors may influence the evolution of translation initiation mechanisms by
      finding that thermophilic species contain significantly more SD-led genes than
      mesophiles. Our results demonstrate that variation in translation initiation
      mechanisms across bacterial species is predictable and is a consequence of
      di?erential life-history strategies related to maximum growth rate and
      environmental-specific constraints.

PMID- 29220490
TI  - Bayesian Inference of Species Networks from Multilocus Sequence Data.
AB  - Reticulate species evolution, such as hybridization or introgression, is
      relatively common in nature. In the presence of reticulation, species
      relationships can be captured by a rooted phylogenetic network, and orthologous
      gene evolution can be modeled as bifurcating gene trees embedded in the species
      network. We present a Bayesian approach to jointly infer species networks and
      gene trees from multilocus sequence data. A novel birth-hybridization process is
      used as the prior for the species network, and we assume a multispecies network
      coalescent prior for the embedded gene trees. We verify the ability of our method
      to correctly sample from the posterior distribution, and thus to infer a species
      network, through simulations. To quantify the power of our method, we reanalyze
      two large data sets of genes from spruces and yeasts. For the three closely
      related spruces, we verify the previously suggested homoploid hybridization event
      in this clade; for the yeast data, we find extensive hybridization events. Our
      method is available within the BEAST 2 add-on SpeciesNetwork, and thus provides
      an extensible framework for Bayesian inference of reticulate evolution.

PMID- 29220491
TI  - CNVcaller: highly efficient and widely applicable software for detecting copy
      number variations in large populations.
AB  - Background: The increasing amount of sequencing data available for a wide variety
      of species can be theoretically used for detecting copy number variations (CNVs)
      at the population level. However, the growing sample sizes and the divergent
      complexity of nonhuman genomes challenge the efficiency and robustness of current
      human-oriented CNV detection methods. Results: Here, we present CNVcaller, a read
      depth method for discovering CNVs in population sequencing data. The
      computational speed of CNVcaller was 1-2 orders of magnitude faster than CNVnator
      and Genome STRiP for complex genomes with thousands of unmapped scaffolds. CNV
      detection of 232 goats required only 1.4 days on a single compute node.
      Additionally, the Mendelian consistency of sheep trios indicated that CNVcaller
      mitigated the influence of high proportions of gaps and misassembled duplications
      in the nonhuman reference genome assembly. Furthermore, multiple evaluations
      using real sheep and human data indicated that CNVcaller achieved the best
      accuracy and sensitivity for detecting duplications. Conclusions: The fast
      generalized detection algorithms included in CNVcaller overcome prior
      computational barriers for detecting CNVs in large-scale sequencing data with
      complex genomic structures. Therefore, CNVcaller promotes population genetic
      analyses of functional CNVs in more species.

PMID- 29220493
TI  - Serum Uric Acid Laboratory Test Request Patterns in Primary Care: How Panels May
      Contribute to Overutilization and Treatment of Asymptomatic Patients.
AB  - Background: To study the variability in the request of serum uric acid (SUA) in
      primary care. Method: A cross-sectional study was designed and conducted at a
      main core laboratory. Spanish laboratories were invited to report their number of
      serum glucose (SG) and SUA tests requested from primary care during 2014. A
      survey was sent to every participant in November 2016 regarding the inclusion of
      SUA in order profiles/panels. The ratio of SUA/SG requests (SUA/SG) was
      calculated and compared between regions, and laboratories depending on whether
      SUA was included or not in a health check profile. Results: 110 laboratories
      participated in the study (59.8% Spanish population). The median SUA/SG ratio was
      0.82 (IQR: 0.25), and 41 laboratories had a ratio over 0.9. There was a
      significant regional variability (P = .008). Laboratories where SUA was not
      included in the "health check profile" had lower SUA/SG indicators (P = .003).
      Conclusion: There was significant regional variability in the request of SUA, and
      an overall over-request. Different regional customs or habits and the inclusion
      of SUA in the health check profile were probable causes behind the observed over
      request.

PMID- 29220492
TI  - HBV-Derived Synthetic Long Peptide Can Boost CD4+ and CD8+ T-Cell Responses in
      Chronic HBV Patients Ex Vivo.
AB  - Background: Vaccination with synthetic long peptides (SLP) is a promising new
      treatment strategy for chronic hepatitis B virus (CHB). SLP can induce broad T
      cell responses for all HLA types. Here we investigated the ability of a prototype
      HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients
      ex vivo. Methods: HBc-SLP was used to assess cross-presentation by monocyte
      derived dendritic cells (moDC) and BDCA1+ blood myeloid DC (mDC) to engineered
      HBV-specific CD8+ T cells. Autologous SLP-loaded and toll-like receptor (TLR)
      stimulated DC were used to activate patient HBc-specific CD8+ and CD4+ T cells.
      Results: HBV-SLP was cross-presented by moDC, which was further enhanced by
      adjuvants. Patient-derived SLP-loaded moDC significantly increased autologous
      HBcAg18-27-specific CD8+ T cells and CD4+ T cells ex vivo. HBV-specific T cells
      were functional as they synthesized tumor necrosis factor-alpha and interferon
      gamma. In 6/7 of patients blockade of PD-L1 further increased SLP effects. Also,
      importantly, patient-derived BDCA1+ mDC cross-presented and activated autologous
      T-cell responses ex vivo. Conclusions: As a proof of concept, we showed a
      prototype HBc-SLP can boost T-cell responses in patients ex vivo. These results
      pave the way for the development of a therapeutic SLP-based vaccine to induce
      effective HBV-specific adaptive immune responses in CHB patients.

PMID- 29220495
TI  - Converting a Liability to an Asset: Using the Clearance of a Malaria Parasite
      Protein From the Blood of Infected Subjects to Predict the Outcome of Treatment.

PMID- 29220494
TI  - SOAPnuke: a MapReduce acceleration-supported software for integrated quality
      control and preprocessing of high-throughput sequencing data.
AB  - Quality control (QC) and preprocessing are essential steps for sequencing data
      analysis to ensure the accuracy of results. However, existing tools cannot
      provide a satisfying solution with integrated comprehensive functions, proper
      architectures, and highly scalable acceleration. In this article, we demonstrate
      SOAPnuke as a tool with abundant functions for a "QC-Preprocess-QC" workflow and
      MapReduce acceleration framework. Four modules with different preprocessing
      functions are designed for processing datasets from genomic, small RNA, Digital
      Gene Expression, and metagenomic experiments, respectively. As a workflow-like
      tool, SOAPnuke centralizes processing functions into 1 executable and predefines
      their order to avoid the necessity of reformatting different files when switching
      tools. Furthermore, the MapReduce framework enables large scalability to
      distribute all the processing works to an entire compute cluster.We conducted a
      benchmarking where SOAPnuke and other tools are used to preprocess a ~30* NA12878
      dataset published by GIAB. The standalone operation of SOAPnuke struck a balance
      between resource occupancy and performance. When accelerated on 16 working nodes
      with MapReduce, SOAPnuke achieved ~5.7 times the fastest speed of other tools.

PMID- 29220496
TI  - Duration of Influenza Vaccine Effectiveness: A Systematic Review, Meta-analysis,
      and Meta-regression of Test-Negative Design Case-Control Studies.
AB  - Background: Whether influenza vaccination offers protection for the duration of
      an influenza season was called into question recently after analysis of data from
      test-negative design (TND) case-control studies. Method: The published literature
      was systematically reviewed to identify TND studies that estimated the change in
      vaccine effectiveness (VE) with respect to time since vaccination. Results:
      Fourteen studies were identified through the literature search as meeting
      eligibility criteria. Meta-analyses were performed to compare VE 15-90 days after
      vaccination to VE 91-180 days after vaccination. A significant decline in VE was
      observed for influenza virus subtype A/H3 (change in VE, -33; 95% confidence
      interval [CI], -57 to -12) and type B (change in VE, -19; 95% CI, -33 to -6). VE
      declined for influenza virus subtype A/H1, but this difference was not
      statistically significant (change in VE -8; 95% CI, -27 to 21). A multivariable
      mixed-effects meta-regression model indicated that the change VE was associated
      with the proportion of study participants who were cases and the proportion who
      were vaccinated controls (P < .05). This could reflect biological effects such as
      (1) mismatch between the vaccine received and the circulating strains (among
      cases), (2) herd immunity (among controls), or (3) the reduced power of
      individual TND studies in the later parts of an influenza outbreak. Conclusions:
      Exploration of new influenza vaccination strategies must be a priority for
      influenza control, particularly in tropical countries with year-round influenza
      virus activity.

PMID- 29220498
TI  - NKG2C Deletion Is a Risk Factor for Human Cytomegalovirus Viremia and Disease
      After Lung Transplantation.
AB  - Human cytomegalovirus (HCMV) replication is limited by HCMV-specific natural
      killer (NK) cell response. Distinct genetic polymorphisms, which are potentially
      involved in antiviral NK cell response, have been described. Here, the
      association between polymorphisms at IgG1 genetic marker 3/17,
      FcgammaRIIIalpha/CD16a 158V/F, NKG2Cwt/del, CD226/rs727088, and rs763361,
      respectively, and HCMV viremia and disease were investigated in 98 lung
      transplant recipients (LTRs), within 9 months after stop of posttransplant HCMV
      prophylaxis. From all variants, only the NKG2Cwt/wt genotype was significantly
      associated with freedom from HCMV viremia (P = .0002) and disease (P = .02),
      compared with the NKG2Cwt/del genotype. Thus, LTRs expressing the homozygous
      NKG2C wild type seem to have a selective advantage in HCMV defense.

PMID- 29220497
TI  - Posttreatment HRP2 Clearance in Patients with Uncomplicated Plasmodium falciparum
      Malaria.
AB  - Background: The response to antimalarial treatment is assessed using serial
      microscopy. New techniques for accurate measurement of the Plasmodium falciparum
      histidine-rich protein 2 (HRP2) antigen have allowed for monitoring of the
      antigen concentration over time, offering a potential alternative for assessing
      treatment response. Methods: Posttreatment HRP2 concentrations were measured in
      samples obtained longitudinally from 537 individuals with P. falciparum malaria
      who were participating in efficacy trials in Angola, Tanzania, and Senegal. The
      HRP2 half-life was estimated using a first-order kinetics clearance model. The
      association between the HRP2 concentration 3 days after treatment and
      recrudescence of infection was assessed. Results: Despite substantial variation
      in HRP2 concentrations among participants at baseline, concentrations
      consistently showed a first-order exponential decline. The median half-life of
      HRP2 was estimated to be 4.5 days (interquartile range [IQR], 3.3-6.6 days) in
      Angola, 4.7 days (IQR, 4.0-5.9 days) in Tanzania, and 3.0 days (IQR, 2.1-4.5
      days) in Senegal. The day 3 HRP2 concentration was predictive of eventual
      recrudescence, with an area under the receiver operating characteristic curve of
      0.86 (95% confidence interval, .73-.99). Conclusions: Consistent HRP2 clearance
      dynamics following successful antimalarial treatment imply a common underlying
      mechanism of biological clearance. Patients who ultimately did not respond to
      treatment did not exhibit this same pattern of clearance, even in the absence of
      other indications of inadequate response to treatment.

PMID- 29220499
TI  - Cohort Profile: Rationale and design of the fourth visit of the STANISLAS cohort:
      a familial longitudinal population-based cohort from the Nancy region of France.

PMID- 29220500
TI  - Toxicities of Selected Essential Oils, Silicone Oils, and Paraffin Oil against
      the Common Bed Bug (Hemiptera: Cimicidae).
AB  - The common bed bug [Cimex lectularius L. (Hemiptera: Cimicidae)] and tropical bed
      bug [Cimex hemipterus F. (Hemiptera: Cimicidae)] resurged in the United States
      and many other countries over the past decades. The need for safe and effective
      bed bug control products propelled the development of numerous 'green
      insecticides', mostly with essential oils listed as active ingredients. Various
      inorganic and organic oils also were used for bed bug management. However, there
      are no published studies on their toxicities against bed bugs. In this study, we
      screened 18 essential oils, three silicone oils, and paraffin oil (C5-20
      paraffins) for their toxicities against bed bugs. All the oils exhibited
      insecticidal activity in topical assays. Their toxicities varied significantly;
      all of the evaluated essential oils were less effective than silicone oils and
      paraffin oil. The LD50 values of the most effective essential oil (blood orange),
      paraffin oil, and the most effective silicone oil (dodecamethylpentasiloxane) are
      0.184 +/- 0.018, 0.069 +/- 0.012, and 0.036 +/- 0.005 mg per bug, respectively.
      Direct spray of 1% water solution of 3-[hydroxy (polyethyleneoxy) propyl]
      heptamethyltrisiloxane, the only silicone oil that mixes well with water,
      resulted in 92% bed bug mortality after 1 d. Results of this study indicate
      silicone oils and paraffin oil have the potential to be used as safer alternative
      bed bug control materials.

PMID- 29220501
TI  - Combination of 247 Genome-Wide Association Studies Reveals High Cancer Risk as a
      Result of Evolutionary Adaptation.
AB  - Analysis of GLOBOCAN-2012 data shows clearly here that cancer incidence worldwide
      is highly related with low average annual temperatures and extreme low
      temperatures. This applies for all cancers together or separately for many
      frequent or rare cancer types (all cancers P = 9.49*10-18). Supporting fact is
      that Inuit people, living at extreme low temperatures, have the highest cancer
      rates today. Hypothesizing an evolutionary explanation, 240 cancer genome-wide
      association studies, and seven genome-wide association studies for cold and high
      altitude adaptation were combined. A list of 1,377 cancer-associated genes was
      created to initially investigate whether cold selected genes are enriched with
      cancer-associated genes. Among Native Americans, Inuit and Eskimos, the highest
      association was observed for Native Americans (P = 6.7*10-5). An overall or a
      meta-analysis approach confirmed further this result. Similar approach for three
      populations living at extreme high altitude, revealed high association for
      Andeans-Tibetans (P = 1.3*10-11). Overall analysis or a meta-analysis was also
      significant. A separate analysis showed special selection for tumor suppressor
      genes. These results can be viewed along with those of previous functional
      studies that showed that reduced apoptosis potential due to specific p53 variants
      (the most important tumor suppressor gene) is beneficial in high-altitude and
      cold environments. In conclusion, this study shows that genetic variants selected
      for adaptation at extreme environmental conditions can increase cancer risk later
      on age. This is in accordance with antagonistic pleiotropy hypothesis.

PMID- 29220502
TI  - Identification of Soybean Host Plant Resistance to Brown Marmorated Stink Bugs in
      Maturity Group III Plant Introductions.
AB  - Halyomorpha halys (Stal; Hemiptera: Pentatomidae), brown marmorated stink bug
      (BMSB), is a polyphagous nonnative insect first found in the United States in
      1996. As of 2017, BMSB has been detected in 43 states and is a severe
      agricultural pest in mid-Atlantic states. On soybean, Glycine max (L.) Merr
      (Fabales: Fabaceae), damage from BMSB infestation ranges from puncture marks with
      seed discoloration and deformities to seed and pod abortion. Host plant
      resistance has been used for managing pest populations and mitigating soybean
      yield losses caused by neotropical stink bugs (Eushistus heros, Nezara viridula,
      and Piezodorus guildinii) in Brazil and on the U.S. Gulf Coast. We evaluated
      maturity group III plant introductions (PIs) for resistance to BMSB damage. In
      2014, field cage choice tests of 106 PIs revealed a range of both BMSB damage
      incidence and severity. In field choice tests, PIs 085665 and 097139 showed the
      lowest incidence of BMSB damage and seed weight loss due to BMSB, while PIs
      243532, 243540, and 567252 had the highest. In whole plant no-choice tests, PIs
      085665 and 097139 also had high levels of resistance. However, PI 085665 had a
      higher incidence of damage but lower seed weight loss than PI 097139, which may
      suggest bimodal resistance. Moreover, PIs 085665 and 097139 are from Japan and
      North Korea, respectively, two geographically isolated countries where BMSB is
      native. Thus, further characterization of host plant resistance to BMSB in each
      of these lines may elucidate distinct mechanisms that could be synergistic if
      stacked in breeding lines.

PMID- 29220504
TI  - Influence of thermodynamically unfavorable secondary structures on DNA
      hybridization kinetics.
AB  - Nucleic acid secondary structure plays an important role in nucleic acid-nucleic
      acid recognition/hybridization processes, and is also a vital consideration in
      DNA nanotechnology. Although the influence of stable secondary structures on
      hybridization kinetics has been characterized, unstable secondary structures,
      which show positive DeltaG degrees  with self-folding, can also form, and their
      effects have not been systematically investigated. Such thermodynamically
      unfavorable secondary structures should not be ignored in DNA hybridization
      kinetics, especially under isothermal conditions. Here, we report that positive
      DeltaG degrees  secondary structures can change the hybridization rate by two
      orders of magnitude, despite the fact that their hybridization obeyed second
      order reaction kinetics. The temperature dependence of hybridization rates showed
      non-Arrhenius behavior; thus, their hybridization is considered to be nucleation
      limited. We derived a model describing how DeltaG degrees  positive secondary
      structures affect hybridization kinetics in stopped-flow experiments with 47
      pairs of oligonucleotides. The calculated hybridization rates, which were based
      on the model, quantitatively agreed with the experimental rate constant.

PMID- 29220503
TI  - Downregulation of Survivin contributes to cell-cycle arrest during postnatal
      cardiac development in a severe spinal muscular atrophy mouse model.
AB  - Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality,
      characterized by progressive degeneration of spinal-cord motor neurons, leading
      to atrophy of skeletal muscles. However, accumulating evidence indicates that it
      is a multi-system disorder, particularly in its severe forms. Several studies
      delineated structural and functional cardiac abnormalities in SMA patients and
      mouse models, yet the abnormalities have been primarily attributed to autonomic
      dysfunction. Here, we show in a severe mouse model that its cardiomyocytes
      undergo G0/G1 cell-cycle arrest and enhanced apoptosis during postnatal
      development. Microarray and real-time RT-PCR analyses revealed that a set of
      genes associated with cell cycle and apoptosis were dysregulated in newborn pups.
      Of particular interest, the Birc5 gene, which encodes Survivin, an essential
      protein for heart development, was down-regulated even on pre-symptomatic
      postnatal day 0. Interestingly, cultured cardiomyocytes depleted of SMN
      recapitulated the gene expression changes including downregulation of Survivin
      and abnormal cell-cycle progression; and overexpression of Survivin rescued the
      cell-cycle defect. Finally, increasing SMN in SMA mice with a therapeutic
      antisense oligonucleotide improved heart pathology and recovered expression of
      deregulated genes. Collectively, our data demonstrate that the cardiac
      malfunction of the severe SMA mouse model is mainly a cell-autonomous defect,
      caused by widespread gene deregulation in heart tissue, particularly of Birc5,
      resulting in developmental abnormalities through cell-cycle arrest and apoptosis.

PMID- 29220505
TI  - Metabolic Characteristics of Recently Diagnosed Adult-Onset Autoimmune Diabetes
      Mellitus.
AB  - Context and Objective: Among patients diagnosed with type 2 diabetes, autoimmune
      diabetes often remains undetected. Metabolic features of these patients are
      insufficiently characterized at present. Design, Setting, and Patients: This
      study compared age- and sex-matched adult (aged 41 to 62 years) humans with
      recent-onset diabetes: patients positive for antibodies against glutamic acid
      decarboxylase (GAD) and/or cytoplasmic islet-cell antigen with an insulin-free
      period of >6 months [antibody positive/insulin negative (ab+/ins-); previously
      termed latent autoimmune diabetes of adults], type 1 diabetes [antibody
      positive/insulin positive (ab+/ins+)], and type 2 diabetes [antibody
      negative/insulin negative (ab-/ins-)], as well as glucose-tolerant humans
      (controls) of the German Diabetes Study (n = 41/group). beta-Cell function was
      assessed from glucagon tests and intravenous glucose tolerance tests (IVGTTs),
      and insulin sensitivity was determined from hyperinsulinemic-euglycemic clamps.
      Results: Of the ab+/ins- patients, 33 (81%) were initially diagnosed as having
      type 2 diabetes. In ab+/ins-, body mass index (BMI) was higher than in ab+/ins+
      (27.8 +/- 5.3 kg/m2 vs 25.0 +/- 3.5 kg/m2, P < 0.05), lower than in ab-/ins-
      (31.9 +/- 5.8 kg/m2, P < 0.05), and similar to controls (29.4 +/- 6.6 kg/m2). In
      ab+/ins-, GAD antibody titers correlated negatively with BMI (r = -0.40, P <
      0.05) and with C-peptide secretion in glucagon stimulation tests (r = -0.33, P <
      0.05). beta-Cell function from IVGTT was 228% higher in ab+/ins- than in ab+/ins+
      but 35% lower than in ab-/ins- and 61% lower than in controls (all P < 0.05).
      Insulin sensitivity in ab+/ins- was comparable to ab+/ins+ and controls but 41%
      higher than in ab-/ins- (P < 0.05) after adjustment for BMI and fasting blood
      glucose or hemoglobin A1c. Conclusion: Even shortly after diagnosis, ab+/ins-
      patients feature partly preserved beta-cell function and chronic hyperglycemia,
      which possibly contributes to the observed impairment of whole-body insulin
      sensitivity.

PMID- 29220507
TI  - Assessing the heterogeneity of in silico plasmid predictions based on whole
      genome-sequenced clinical isolates.
AB  - High-throughput next-generation shotgun sequencing of pathogenic bacteria is
      growing in clinical relevance, especially for chromosomal DNA-based taxonomic
      identification and for antibiotic resistance prediction. Genetic exchange is
      facilitated for extrachromosomal DNA, e.g. plasmid-borne antibiotic resistance
      genes. Consequently, accurate identification of plasmids from whole-genome
      sequencing (WGS) data remains one of the major challenges for sequencing-based
      precision medicine in infectious diseases. Here, we assess the heterogeneity of
      four state-of-the-art tools (cBar, PlasmidFinder, plasmidSPAdes and Recycler) for
      the in silico prediction of plasmid-derived sequences from WGS data.
      Heterogeneity, sensitivity and precision were evaluated by reference-independent
      and reference-dependent benchmarking using 846 Gram-negative clinical isolates.
      Interestingly, the majority of predicted sequences were tool-specific, resulting
      in a pronounced heterogeneity across tools for the reference-independent
      assessment. In the reference-dependent assessment, sensitivity and precision
      values were found to substantially vary between tools and across taxa, with cBar
      exhibiting the highest median sensitivity (87.45%) but a low median precision
      (27.05%). Furthermore, integrating the individual tools into an ensemble approach
      showed increased sensitivity (95.55%) while reducing the precision (25.62%). CBar
      and plasmidSPAdes exhibited the strongest concordance with respect to identified
      antibiotic resistance factors. Moreover, false-positive plasmid predictions
      typically contained only few antibiotic resistance factors. In conclusion, while
      high degrees of heterogeneity and variation in sensitivity and precision were
      observed across the different tools and taxa, existing tools are valuable for
      investigating the plasmid-borne resistome. Nevertheless, additional studies on
      representative clinical data sets will be necessary to translate in silico
      plasmid prediction approaches from research to clinical application.

PMID- 29220508
TI  - Model-based design of bistable cell factories for metabolic engineering.
AB  - Motivation: Metabolism can exhibit dynamic phenomena like bistability due to the
      presence of regulatory motifs like the positive feedback loop. As cell factories,
      microorganisms with bistable metabolism can have a high and a low product flux at
      the two stable steady states, respectively. The exclusion of metabolic regulation
      and network dynamics limits the ability of pseudo-steady state stoichiometric
      models to detect the presence of bistability, and reliably assess the outcomes of
      design perturbations to metabolic networks. Results: Using kinetic models of
      metabolism, we assess the change in the bistable characteristics of the network,
      and suggest designs based on perturbations to the positive feedback loop to
      enable the network to produce at its theoretical maximum rate. We show that the
      most optimal production design in parameter space, for a small bistable metabolic
      network, may exist at the boundary of the bistable region separating it from the
      monostable region of low product fluxes. The results of our analysis can be
      broadly applied to other bistable metabolic networks with similar positive
      feedback network topologies. This can complement existing model-based design
      strategies by providing a smaller number of feasible designs that need to be
      tested in vivo. Availability and implementation:
      http://lmse.biozone.utoronto.ca/downloads/. Contact:
      krishna.mahadevan@utoronto.ca. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29220506
TI  - A Molecular Portrait of De Novo Genes in Yeasts.
AB  - New genes, with novel protein functions, can evolve "from scratch" out of
      intergenic sequences. These de novo genes can integrate the cell's genetic
      network and drive important phenotypic innovations. Therefore, identifying de
      novo genes and understanding how the transition from noncoding to coding occurs
      are key problems in evolutionary biology. However, identifying de novo genes is a
      difficult task, hampered by the presence of remote homologs, fast evolving
      sequences and erroneously annotated protein coding genes. To overcome these
      limitations, we developed a procedure that handles the usual pitfalls in de novo
      gene identification and predicted the emergence of 703 de novo gene candidates in
      15 yeast species from 2 genera whose phylogeny spans at least 100 million years
      of evolution. We validated 85 candidates by proteomic data, providing new
      translation evidence for 25 of them through mass spectrometry experiments. We
      also unambiguously identified the mutations that enabled the transition from
      noncoding to coding for 30 Saccharomyces de novo genes. We established that de
      novo gene origination is a widespread phenomenon in yeasts, only a few being
      ultimately maintained by selection. We also found that de novo genes
      preferentially emerge next to divergent promoters in GC-rich intergenic regions
      where the probability of finding a fortuitous and transcribed ORF is the highest.
      Finally, we found a more than 3-fold enrichment of de novo genes at recombination
      hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic
      recombination contributes to de novo gene emergence in yeasts.

PMID- 29220509
TI  - Community effort endorsing multiscale modelling, multiscale data science and
      multiscale computing for systems medicine.
AB  - Systems medicine holds many promises, but has so far provided only a limited
      number of proofs of principle. To address this road block, possible barriers and
      challenges of translating systems medicine into clinical practice need to be
      identified and addressed. The members of the European Cooperation in Science and
      Technology (COST) Action CA15120 Open Multiscale Systems Medicine (OpenMultiMed)
      wish to engage the scientific community of systems medicine and multiscale
      modelling, data science and computing, to provide their feedback in a structured
      manner. This will result in follow-up white papers and open access resources to
      accelerate the clinical translation of systems medicine.

PMID- 29220510
TI  - Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but
      not ciliogenesis.
AB  - The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B
      complexes mediates ciliary protein trafficking. Mutations in the genes encoding
      the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and
      IFT144) are known to cause skeletal ciliopathies, including cranioectodermal
      dysplasia (CED). As the IFT122 subunit connects the core and peripheral
      subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the
      complex. Indeed, we here showed that knockout (KO) of the IFT122 gene in hTERT
      RPE1 cells using the CRISPR/Cas9 system led to a severe ciliogenesis defect,
      whereas KO of other IFT-A genes had minor effects on ciliogenesis but impaired
      ciliary protein trafficking. Exogenous expression of not only wild-type IFT122
      but also its CED-associated missense mutants, which fail to interact with other
      IFT-A subunits, rescued the ciliogenesis defect of IFT122-KO cells. However,
      IFT122-KO cells expressing CED-type IFT122 mutants showed defects in ciliary
      protein trafficking, such as ciliary entry of Smoothened in response to Hedgehog
      signaling activation. The trafficking defects partially resembled those observed
      in IFT144-KO cells, which demonstrate failed assembly of the functional IFT-A
      complex at the base of cilia. These observations make it likely that, although
      IFT122 is essential for ciliogenesis, CED-type missense mutations underlie a
      skeletal ciliopathy phenotype by perturbing ciliary protein trafficking with
      minor effects on ciliogenesis per se.

PMID- 29220511
TI  - Unbiased estimate of synonymous and non-synonymous substitution rates with non
      stationary base composition.
AB  - The measurement of synonymous and non-synonymous substitution rates (dS and dN)
      is useful for assessing selection operating on protein sequences or for
      investigating mutational processes affecting genomes. In particular, the ratio
      dNdS is expected to be a good proxy for omega, the ratio of fixation robabilities
      of non-synonymous mutations relative to that of neutral mutations. Standard
      methods for estimating dN, dS or omega rely on the assumption that the base
      composition of sequences is at the equilibrium of the evolutionary process. In
      many clades, this assumption of stationarity is in fact incorrect, and we show
      here through simulations and analyses of empirical data that non-stationarity
      biases the estimate of dN, dS and omega. We show that the bias in the estimate of
      omega can be fixed by explicitly taking into onsideration non-stationarity in the
      modeling of codon evolution, in a maximum likelihood framework. Moreover, we
      propose an exact method for estimating dN and dS on branches, based on stochastic
      mapping, that can take into account non-stationarity. This method can be directly
      applied to any kind of codon evolution model, as long as neutrality is clearly
      parameterized.

PMID- 29220512
TI  - A survey and evaluations of histogram-based statistics in alignment-free sequence
      comparison.
AB  - Motivation: Since the dawn of the bioinformatics field, sequence alignment scores
      have been the main method for comparing sequences. However, alignment algorithms
      are quadratic, requiring long execution time. As alternatives, scientists have
      developed tens of alignment-free statistics for measuring the similarity between
      two sequences. Results: We surveyed tens of alignment-free k-mer statistics.
      Additionally, we evaluated 33 statistics and multiplicative combinations between
      the statistics and/or their squares. These statistics are calculated on two k-mer
      histograms representing two sequences. Our evaluations using global alignment
      scores revealed that the majority of the statistics are sensitive and capable of
      finding similar sequences to a query sequence. Therefore, any of these statistics
      can filter out dissimilar sequences quickly. Further, we observed that
      multiplicative combinations of the statistics are highly correlated with the
      identity score. Furthermore, combinations involving sequence length difference or
      Earth Mover's distance, which takes the length difference into account, are
      always among the highest correlated paired statistics with identity scores.
      Similarly, paired statistics including length difference or Earth Mover's
      distance are among the best performers in finding the K-closest sequences.
      Interestingly, similar performance can be obtained using histograms of shorter
      words, resulting in reducing the memory requirement and increasing the speed
      remarkably. Moreover, we found that simple single statistics are sufficient for
      processing next-generation sequencing reads and for applications relying on local
      alignment. Finally, we measured the time requirement of each statistic. The
      survey and the evaluations will help scientists with identifying efficient
      alternatives to the costly alignment algorithm, saving thousands of computational
      hours. Availability: The source code of the benchmarking tool is available as
      Supplementary Materials.

PMID- 29220513
TI  - Integrating 5hmC and gene expression data to infer regulatory mechanisms.
AB  - Motivation: Epigenetic mechanisms are known to play a major role in breast
      cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied.
      We hypothesize that 5hmC mediates redox regulation of gene expression in an
      aggressive subtype known as triple negative breast cancer (TNBC). To address
      this, our objective was to highlight genes that may be the target of this process
      by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC
      changes associated with mRNA changes in TNBC cells. Results: We proceeded to
      develop an approach to integrate novel Pvu-sequencing and RNA-sequencing data.
      The result of our approach to merge genome-wide, high-throughput TNBC cell line
      datasets to identify significant, concordant 5hmC and mRNA changes in response to
      antioxidant treatment produced a gene set with relevance to cancer stem cell
      function. Moreover, we have established a method that will be useful for
      continued research of 5hmC in TNBC cells and tissue samples. Availability and
      implementation: Data are available at Gene Expression Omnibus (GEO) under
      accession number GSE103850. Contact: bollig@karmanos.org.

PMID- 29220514
TI  - The influence of social norms on flu vaccination among African American and White
      adults.
AB  - Adult influenza vaccination rates remain suboptimal, particularly among African
      Americans. Social norms may influence vaccination behavior, but little research
      has focused on influenza vaccine and almost no research has focused on racially
      specific norms. This mixed methods investigation utilizes qualitative interviews
      and focus groups (n = 118) and national survey results (n = 1643) to assess both
      descriptive and subjective norms surrounding influenza vaccination. Qualitative
      results suggest a perceived descriptive norm that 'about half' of the population
      gets vaccinated. Participants describe differing norms by race and vaccine
      behavior. Quantitative results confirm a perceived descriptive norm that 40-60%
      of the population gets vaccinated. Both African Americans and Whites accurately
      identified race-specific vaccination rates relative to the general population.
      Individuals who report that a majority of people around them want them to be
      vaccinated were significantly more likely to be vaccinated, suggesting subjective
      norms are influential for both White and African American adults. While perceived
      descriptive norms are somewhat accurate (mirroring the actual influenza
      vaccination rate), emphasizing a suboptimal vaccination rate may not be
      beneficial. Health promotion efforts, particularly those targeting African
      Americans, may benefit from focusing on subjective norms and encouraging friends
      and family members to talk about the benefits of influenza vaccination.

PMID- 29220515
TI  - BUSCO applications from quality assessments to gene prediction and phylogenomics.
AB  - Genomics promises comprehensive surveying of genomes and metagenomes, but rapidly
      changing technologies and expanding data volumes make evaluation of completeness
      a challenging task. Technical sequencing quality metrics can be complemented by
      quantifying completeness of genomic datasets in terms of the expected gene
      content of Benchmarking Universal Single-Copy Orthologs (BUSCO,
      http://busco.ezlab.org). The latest software release implements a complete
      refactoring of the code to make it more flexible and extendable to facilitate
      high-throughput assessments. The original six lineage assessment datasets have
      been updated with improved species sampling, 34 new subsets have been built for
      vertebrates, arthropods, fungi, and prokaryotes that greatly enhance resolution,
      and datasets are now also available for nematodes, protists, and plants. Here we
      present BUSCO v3 with example analyses that highlight the wide-ranging utility of
      BUSCO assessments, which extend beyond quality control of genomics datasets to
      applications in comparative genomics analyses, gene predictor training,
      metagenomics, and phylogenomics.

PMID- 29220517
TI  - Determining the Effectiveness of Three-Gene Pyramids Against Aphis glycines
      (Hemiptera: Aphididae) Biotypes.
AB  - Since the discovery of Aphis glycines Matsumura (Hemiptera: Aphididae) in the
      United States, the primary management tactic has been foliar insecticides.
      Alternative management options such as host plant resistance to A. glycines have
      been developed and their effectiveness proved. However, the use of host plant
      resistance was complicated by the discovery of multiple, virulent biotypes of A.
      glycines in the United States that are capable of overcoming single Rag genes,
      Rag1 and Rag2, as well as a two-gene pyramid of Rag1+Rag2. However, current
      models predict that the virulent allele frequency of A. glycines decreases in
      response to the use of pyramided Rag genes, suggesting that pyramids represent a
      more sustainable use of these traits. Previous research has demonstrated that
      virulent biotypes can be effectively managed using a three-gene pyramid of
      Rag1+Rag2+Rag3. Additional Rag-genes have been discovered (Rag4 and Rag5), but
      whether the incorporation of these genes into novel three-gene pyramids will
      improve efficacy is not known. We tested single-gene (Rag1 and Rag2) and pyramid
      cultivars (Rag1+Rag2, Rag1+Rag2+Rag3, Rag1+Rag2+Rag4) to multiple biotypes in
      laboratory assays. Our results confirm that the Rag1+Rag2+Rag3 pyramid
      effectively manages all known A. glycines biotypes when compared with cultivars
      that are overcome by the associated biotype. Our results indicate that
      Rag1+Rag2+Rag4 would be an effective management option for biotype-1, biotype-2,
      and biotype-3 A. glycines, but had a negligible impact on biotype-4.

PMID- 29220516
TI  - Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous
      Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).
AB  - Conventional insecticide assays, which measure the effects of insecticide
      exposure on short-term mortality, overlook important traits, including
      persistence of toxicity or sub-lethal effects. Therefore, such approaches are
      especially inadequate for prediction of the overall impact of insecticides on
      beneficial arthropods. In this study, the side effects of four modern
      insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and
      spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were
      evaluated under laboratory conditions by exposition on treated potted plants. In
      addition to investigation of acute toxicity and persistence of harmful activity
      in both larvae and adults of A. bipunctata, demographic parameters were
      evaluated, to provide a comprehensive picture of the nontarget effects of these
      products. Field doses of the four insecticides caused detrimental effects to A.
      bipunctata; but in different ways. Overall, spinosad showed the best
      toxicological profile among the products tested. Emamectin benzoate could be
      considered a low-risk insecticide, but had high persistence. Chlorantraniliprole
      exhibited lethal effects on early instar larvae and adults, along with a long
      lasting activity, instead spirotetramat showed a low impact on larval and adult
      mortality and can be considered a short-lived insecticide. However, demographic
      analysis demonstrated that chlorantraniliprole and spirotetramat caused sub
      lethal effects. Our findings highlight that sole assessment of mortality can lead
      to underestimation of the full impact of pesticides on nontarget insects.
      Demographic analysis was demonstrated to be a sensitive method for detection of
      the sub-lethal effects of insecticides on A. bipunctata, and this approach should
      be considered for evaluation of insecticide selectivity.

PMID- 29220518
TI  - Temperature-Dependent Development of Oligota flavicornis (Coleoptera:
      Staphylinidae) Preying on Tetranychus cinnabarinus (Acarina: Tetranychidae).
AB  - The effect of nine constant temperatures on developmental time of Oligota
      flavicornis (Boisduval and Lacordaire) preying on Tetranychus cinnabarinus
      (Boisduval) (Acari: Tetranychidae) eggs was determined under laboratory
      conditions of 75 +/- 5% RH and a 16:8 (L:D) h photoperiod. O. flavicornis
      survival rates were highest between 18 and 30 degrees C, although O. flavicornis
      eggs developed successfully to adults at 12-32 degrees C, and the developmental
      durations to adult at the seven temperatures (12, 15, 18, 20, 25, 30, and 32
      degrees C) were 114.41, 51.66, 33.45, 23.21, 13.43, 11.54, and 17.18 d,
      respectively. Two linear and seven nonlinear models (Logan-6 and Logan-10,
      Taylor, Lactin-1 and Lactin-2, and Briere-1 and Briere-2) were fit to the
      developmental rates of the immature predatory stages to estimate the thermal
      constant (K) and critical temperatures. The lower temperature threshold (T0) and
      K for the immature stages using the common linear model were 9.96 degrees C and
      225.73 degree-days and Ikemoto-Takai linear model were 11.01 degrees C and 167.14
      degree-days, respectively. The upper temperature threshold values estimated by
      the Logan-6 and Lactin-1 models were both 34.86 degrees C. The T0 values
      estimated by the Briere-1 and Briere-2 models were 10.67 and 9.32 degrees C for
      all immature stages, respectively, and the estimated optimal temperature
      according to the Briere-2 model was 29.59 degrees C. Therefore, the two linear
      models and Briere-2 model estimates approximated the actual relationship between
      the temperature and developmental rate of immature O. flavicornis.

PMID- 29220519
TI  - Aggregation Patterns, Sampling Plan, and Economic Injury Levels for the New
      Citrus Pest Delottococcus aberiae (Hemiptera: Pseudococcidae).
AB  - Delottococcus aberiae De Lotto (Hemiptera: Pseudococcidae) is the latest exotic
      mealybug species introduced in citrus in the Mediterranean basin. It causes
      severe distortion and size reduction on developing fruits. Due to its first
      interaction with citrus, D. aberiae economic thresholds are still unknown for
      this crop and the current Integrated Pest Management programs have been
      disrupted. The objectives of this study were to determine the aggregation
      patterns of D. aberiae in citrus, develop an efficient sampling plan to assess
      its population density, and calculate its Economic and Economic Environmental
      Injury Levels (EIL and EEIL, respectively). Twelve and 19 orchards were sampled
      in 2014 and 2015, respectively. At each orchard, population densities were
      monitored fortnightly in leaves, twigs, and fruit, and fruit damage was
      determined at harvest. Our results showed a clumped aggregation of D. aberiae in
      all organs with no significant differences between generations on fruit. Fruit
      damage at harvest was strongly correlated with fruit occupation in spring. Based
      on these results and using chlorpyrifos as the insecticide of reference, the EIL
      and EEIL were calculated as 7.1 and 12.1% of occupied fruit in spring,
      respectively. With all this, we recommend sampling 275 fruits using a binomial
      sampling method or alternatively, 140 fruits with an enumerative method bimonthly
      between petal fall and July.

PMID- 29220520
TI  - Gaps in Workplace Education For Prevention of Occupational Skin Disease.
AB  - Background: Occupational contact dermatitis (OCD) is a common occupational
      disease. Evidence suggests that education and training are effective prevention
      strategies. In spite of these known prevention strategies, workers continue to
      develop OCD. Little is reported regarding the actual training experience of
      workers. Objective: To examine the training experience of workers with contact
      dermatitis to identify areas for improvement. Methods: Participants were workers
      being assessed for contact dermatitis in an occupational health clinic. The
      anonymous survey collected demographics, workplace characteristics, and education
      and prevention practices. Results: Approximately 80% reported general
      occupational health and safety training; however, only 49% reported skin-specific
      training (SST). For workers reporting SST, most received information regarding
      exposure avoidance, hand washing, and glove use. This content was reported as
      helpful by at least 50%. Workers who did not receive SST indicated the most
      important content would be warning signs of skin problems, how to avoid exposure
      and skin care while using gloves. Conclusions: While the study was anonymous and
      used self-reported of training experience, the study suggests there are gaps in
      skin protection training. Addressing these gaps may lead to improved prevention
      and reduction in OCD.

PMID- 29220521
TI  - Trypanosomatid mitochondrial RNA editing: dramatically complex transcript
      repertoires revealed with a dedicated mapping tool.
AB  - RNA editing by targeted insertion and deletion of uridine is crucial to generate
      translatable mRNAs from the cryptogenes of the mitochondrial genome of
      kinetoplastids. This type of editing consists of a stepwise cascade of reactions
      generally proceeding from 3' to 5' on a transcript, resulting in a population of
      partially edited as well as pre-edited and completely edited molecules for each
      mitochondrial cryptogene of these protozoans. Often, the number of uridines
      inserted and deleted exceed the number of nucleotides that are genome-encoded.
      Thus, analysis of kinetoplastid mitochondrial transcriptomes has proven
      frustratingly complex. Here we present our analysis of Leptomonas pyrrhocoris
      mitochondrial cDNA deep sequencing reads using T-Aligner, our new tool which
      allows comprehensive characterization of RNA editing, not relying on targeted
      transcript amplification and on prior knowledge of final edited products. T
      Aligner implements a pipeline of read mapping, visualization of all editing
      states and their coverage, and assembly of canonical and alternative translatable
      mRNAs. We also assess T-Aligner functionality on a more challenging deep
      sequencing read input from Trypanosoma cruzi. The analysis reveals that
      transcripts of cryptogenes of both species undergo very complex editing that
      includes the formation of alternative open reading frames and whole categories of
      truncated editing products.

PMID- 29220523
TI  - Interviewers' Ratings of Respondents' Health: Predictors and Association With
      Mortality.
AB  - Objectives: Recent research indicates that survey interviewers' ratings of
      respondents' health (IRH) may provide supplementary health information about
      respondents in surveys of older adults. Although IRH is a potentially promising
      measure of health to include in surveys, our understanding of the factors
      contributing to IRH remains incomplete. Methods: We use data from the 2011 face
      to-face wave of the Wisconsin Longitudinal Study, a longitudinal study of older
      adults from the Wisconsin high school class of 1957 and their selected siblings.
      We first examine whether a range of factors predict IRH: respondents'
      characteristics that interviewers learn about and observe as respondents answer
      survey questions, interviewers' evaluations of some of what they observe, and
      interviewers' characteristics. We then examine the role of IRH, respondents' self
      rated health (SRH), and associated factors in predicting mortality over a 3-year
      follow-up. Results: As in prior studies, we find that IRH is associated with
      respondents' characteristics. In addition, this study is the first to document
      how IRH is associated with both interviewers' evaluations of respondents and
      interviewers' characteristics. Furthermore, we find that the association between
      IRH and the strong criterion of mortality remains after controlling for
      respondents' characteristics and interviewers' evaluations of respondents.
      Discussion: We propose that researchers incorporate IRH in surveys of older
      adults as a cost-effective, easily implemented, and supplementary measure of
      health.

PMID- 29220524
TI  - Brain Responses to Cigarette-Related and Emotional Images in Smokers During
      Smoking Cessation: No Effect of Varenicline or Bupropion on the Late Positive
      Potential.
AB  - Introduction: Varenicline and bupropion are two effective smoking cessation
      pharmacotherapies. Researchers have hypothesized that they might be effective, in
      part, because they reduce cue reactivity and cue-induced cravings. Here, we used
      event-related potentials (ERPs) to directly measure brain responses to cigarette
      related and other motivationally relevant images during a pharmacologically aided
      quit attempt. Methods: Smokers involved in a 12-week placebo-controlled double
      blind clinical trial of smoking cessation medications (varenicline, bupropion,
      placebo) took part in the study. We assessed participants at two time points: 24
      hours (n = 140) and four weeks (n = 176) after the quit date. At both sessions,
      we measured the amplitude of the Late Positive Potential (LPP), an ERP component
      reliably associated with motivational relevance, and self-reported tonic craving
      using the brief version of the Questionnaire of Smoking Urges (QSU-Brief).
      Results: At both sessions, emotional and cigarette-related images evoked
      significantly larger LPPs than neutral images. Neither drug type nor smoking
      abstinence altered this effect at either session. At both sessions, varenicline
      and bupropion significantly reduced self-reported tonic craving relative to the
      placebo condition. Conclusions: While both varenicline and bupropion reduced self
      reported tonic craving, neither medication altered the amplitude of the LPP to
      cigarette-related or emotional pictures in smokers attempting to quit. These
      medications may influence abstinence by means other than by reducing
      neuroaffective responses to cigarette-related cues. Smokers should be prepared
      for the likelihood that even after several weeks of successful abstinence, once
      treatment ends, cigarette-related cues may remain motivationally relevant and
      trigger cravings that might lead to relapse. Implications: Bupropion and
      varenicline do not alter electrophysiological responses, as measured by the LPP,
      to cigarette-related and emotional images. These findings help explain why
      cigarette-related cues can trigger relapse when smoking cessation medication
      treatments end.

PMID- 29220522
TI  - Meta-analysis of genome-wide association studies identifies 8 novel loci involved
      in shape variation of human head hair.
AB  - Shape variation of human head hair shows striking variation within and between
      human populations, while its genetic basis is far from being understood. We
      performed a series of genome-wide association studies (GWASs) and replication
      studies in a total of 28 964 subjects from 9 cohorts from multiple geographic
      origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23
      ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13
      HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones
      (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14
      LINC00708/GATA3), all showing genome-wide significant association with hair shape
      (P < 5e-8). All except one (1p36.22 PEX14) were replicated with nominal
      significance in at least one of the 6 additional cohorts of European, Native
      American and East Asian origins. Three additional previously known genes (EDAR,
      OFCC1, and PRSS53) were confirmed at the nominal significance level. A
      multivariable regression model revealed that 14 SNPs from different genes
      significantly and independently contribute to hair shape variation, reaching a
      cross-validated AUC value of 0.66 (95% CI: 0.62-0.70) and an AUC value of 0.64 in
      an independent validation cohort, providing an improved accuracy compared with a
      previous model. Prediction outcomes of 2504 individuals from a multiethnic sample
      were largely consistent with general knowledge on the global distribution of hair
      shape variation. Our study thus delivers target genes and DNA variants for future
      functional studies to further evaluate the molecular basis of hair shape in
      humans.

PMID- 29220525
TI  - Impact of Opioid Dose Reduction and Risk Mitigation Initiatives on Chronic Opioid
      Therapy Patients at Higher Risk for Opioid-Related Adverse Outcomes.
AB  - Objective: We aimed to determine if opioid risk reduction initiatives including
      dose reduction and risk mitigation strategies for chronic noncancer pain patients
      receiving chronic opioid therapy (COT) had a differential impact on average daily
      opioid doses of COT patients at higher risk for opioid-related adverse outcomes
      compared with lower-risk patients. Design: Interrupted time series. Setting:
      Group Health Cooperative (GH), a health care delivery system and insurance within
      Washington State, between 2006 and 2014. Population: GH enrollees on COT defined
      as receiving a supply of 70 or more days of opioids within 90 days using
      electronic pharmacy data for filled prescriptions. Methods: We compared the
      average daily morphine equivalent doses (MED) of COT patients with and without
      each of the following higher-risk characteristics: mental disorders, substance
      use disorders, sedative use, and male gender. Results: In all four pairwise
      comparisons, the higher-risk subgroup had a higher average daily MED than the
      lower-risk subgroup across the study period. Adjusted for covariates, modest
      differences in the annual rate of reduction in average daily MED were noted
      between higher- and lower-risk subgroups in three pairwise comparisons: those
      with mental disorders vs without (-8.2 mg/y vs -5.2 mg/y, P = 0.005), with
      sedative use vs without (-9.2 mg/y vs -5.8 mg/y, P = 0.004); mg), in men vs women
      (-8.8 mg/y vs -5.9 mg/y, P = 0.01). Conclusions: Using clinical policy
      initiatives in a health care system, dose reductions were achieved among COT
      patients at higher risk for opioid-related adverse outcomes that were at least as
      large as those among lower-risk patients.

PMID- 29220526
TI  - Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.
AB  - Context: Immune checkpoint inhibitors, including anti-programmed cell death
      protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti
      cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been
      widely used in cancer treatment. They are known to cause immune-related adverse
      events (irAEs), which resemble autoimmune diseases. Anterior pituitary
      hypophysitis with secondary hypopituitarism is a frequently reported irAE,
      especially in patients receiving anti-CTLA4 treatment. In contrast, posterior
      pituitary involvement, such as central diabetes insipidus (DI), is relatively
      rare and is unreported in patients undergoing PD-1/PD-L1 blockade. Case
      Description: We describe a case of a 73-year-old man with Merkel cell carcinoma
      who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial
      response. The patient developed nocturia, polydipsia, and polyuria 3 months after
      starting avelumab. Further laboratory testing revealed central DI. Avelumab was
      held and he received desmopressin for the management of central DI. Within 6
      weeks after discontinuation of avelumab, the patient's symptoms resolved and he
      was eventually taken off desmopressin. The patient remained off avelumab and
      there were no signs or symptoms of DI 2 months after the discontinuation of
      desmopressin. Conclusion: To our knowledge, this is the first report of central
      DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was
      successfully managed by holding treatment with the immune checkpoint inhibitor.
      This case highlights the importance of early screening and appropriate management
      of hormonal irAEs in subjects undergoing treatment with immune checkpoint
      inhibitors to minimize morbidity and mortality.

PMID- 29220527
TI  - Inverse Association Between Neck Pain and All-Cause Mortality in Community
      Dwelling Older Adults.
AB  - Objective: In a previous study, we found an apparent protective effect of neck
      pain on all-cause mortality in subjects older than age 85 years. The present
      longitudinal investigation was performed to verify this unexpected finding in a
      larger sample and to establish its significance. Design: Population follow-up
      study. Setting: Three towns of Northern Italy. Subjects: We examined 5,253
      community-dwelling residents age 65-102 years (55% female). Methods: Through a
      postal questionnaire, baseline information was obtained concerning cardiovascular
      risk factors, self-rated health, physical activity, cardiovascular events,
      medical therapy, and presence of pain in the main joints. Seven-year all-cause
      mortality was the end point. Results: During follow-up, 1,250 people died. After
      adjustment for age, sex, anti-inflammatory drugs, physical activity, and main
      risk factors, neck pain was inversely associated with mortality (hazard ratio =
      0.74, 95% confidence interval = 0.64-0.86, P < 0.001). This association was
      present, with high significance, in each of the eight following subgroups: men,
      women, age 65-74 years, age 75-84 years, age >=85 years and residents of each of
      the three towns. The subjects without neck pain (N = 3,158) were older, more
      often men, less often hypercholesterolemic, less physically active, and had more
      frequently had a stroke than the subjects with neck pain (N = 2,095). There were
      no differences in the causes of death between subjects with or without neck pain.
      Conclusions: This study has confirmed the existence of an independent inverse
      association between neck pain and mortality in the elderly, suggesting that
      reduced sensitivity to neck pain may be a new marker of frailty.

PMID- 29220528
TI  - Maternal Thyroid Function in Early Pregnancy and Neuropsychological Performance
      of the Child at 5 Years of Age.
AB  - Context: Abnormal maternal thyroid function in pregnancy may impair fetal brain
      development, but more evidence is needed to refine and corroborate the
      hypothesis. Objective: To estimate the association between maternal thyroid
      function in early pregnancy and neuropsychological performance of the child at 5
      years of age. Design: Follow-up study. Participants: A cohort of 1153 women and
      their children sampled from the Danish National Birth Cohort. Maternal thyroid
      stimulating hormone (TSH) and free thyroxine (fT4) were measured in stored
      biobank sera from early pregnancy. Main outcomes measures: Child
      neuropsychological test results (Wechsler Intelligence Scale/Test of Everyday
      Attention), test of motor function (Movement Assessment Battery), and results of
      parent and teacher reports (Behavior Rating Inventory of Executive
      Function/Strengths and Difficulties Questionnaire). Results: Altogether 145
      children (12.6%) were born to mothers with abnormal thyroid function in the early
      pregnancy. High maternal TSH and low fT4 were associated with lower child verbal
      intelligence quotient (adjusted mean difference TSH >= 10 mIU/L vs 0.1 to 2.49
      mIU/L, -8.9 [95% confidence interval (CI), -15 to -2.4]; fT4 < 10 pmol/l vs 12.0
      to 18.99 pmol/l, -13 [95% CI, -19 to -7.3]). Abnormal maternal thyroid function
      was also associated with adverse motor function and teacher-reported problems of
      executive function and behavior, and these associations were dominated by
      exposure to maternal hypothyroxinemia. Conclusions: Maternal thyroid hormone
      abnormalities were associated with adverse neuropsychological function of the
      child at 5 years of age. For intelligence, marked hypothyroidism was important,
      whereas for motor function and executive and behavior problems, maternal
      hypothyroxinemia was predominant.

PMID- 29220529
TI  - Oxytocin and Naltrexone Successfully Treat Hypothalamic Obesity in a Boy Post
      Craniopharyngioma Resection.
AB  - Context: Hypothalamic obesity, a treatment-resistant condition common to
      survivors of craniopharyngioma (CP), is strongly associated with a poor quality
      of life in this population. Oxytocin (OT), a hypothalamic neuropeptide, has been
      shown to play a role in the regulation of energy balance and to have anorexigenic
      effects in animal studies. Naltrexone (NAL), an opiate antagonist, has been shown
      to deter hedonic eating and to potentiate OT's effects. Design: In this parent
      observed study, we tested the administration of intranasal OT for 10 weeks (phase
      1), followed by a combination of intranasal OT and NAL for 38 weeks (phase 2) in
      a 13-year-old male with confirmed hypothalamic obesity and hyperphagia post-CP
      resection. Treatment resulted in 1) reduction in body mass index (BMI) z score
      from 1.77 to 1.49 over 10 weeks during phase 1; 2) reduction in BMI z score from
      1.49 to 0.82 over 38 weeks during phase 2; 3) reduced hyperphagia during phases 1
      and 2; 4) continued hedonic high-carbohydrate food-seeking in the absence of
      hunger during phases 1 and 2; and 5) sustained weight reduction during decreased
      parental monitoring and free access to unlocked food in the home during the last
      10 weeks of phase 2. Conclusion: This successful intervention of CP-related
      hypothalamic obesity and hyperphagia by OT alone and in combination with NAL is
      promising for conducting future studies of this treatment-recalcitrant form of
      obesity.

PMID- 29220530
TI  - Impaired Lipolysis, Diminished Fat Oxidation, and Metabolic Inflexibility in
      Obese Girls With Polycystic Ovary Syndrome.
AB  - Context: Metabolic flexibility reflects the ability to switch from lipid to
      carbohydrate oxidation during insulin stimulation manifested in increased
      respiratory quotient (RQ). Little is known about adipose tissue metabolism and
      metabolic flexibility in adolescent girls with polycystic ovary syndrome (PCOS).
      Objective: We investigated whole-body lipolysis, substrate oxidation, and
      metabolic flexibility in obese girls with PCOS vs obese girls without PCOS.
      Patients/Design: Twenty-one obese girls with PCOS and 21 obese girls without PCOS
      were pair-matched for age and race. Body composition, abdominal visceral adipose
      tissue (VAT), sex hormones, lipid profile, and adiponectin were measured. Whole
      body lipolysis ([2H5]glycerol turnover), RQ, and substrate oxidation (indirect
      calorimetry) were evaluated during fasting and a hyperinsulinemic-euglycemic
      clamp together with assessment of insulin sensitivity (IS). Results: Despite
      similar body mass index and percent body fat, girls with PCOS vs girls without
      PCOS had lower fasting lipolysis and fat oxidation, less increase in RQ during
      hyperinsulinemia with impaired suppression in lipolysis and lipid oxidation, and
      lower IS. In multiple regression, the best predictors of metabolic flexibility
      were [using clinical parameters: adiponectin, fasting triglycerides, and insulin
      (R2 = 0.618, P < 0.0001); using research parameters: IS, VAT, and baseline RQ (R2
      = 0.756, P < 0.0001)]. Conclusions: Obese girls with PCOS vs obese girls without
      PCOS have decreased lipid mobilization, diminished fat oxidation, and metabolic
      inflexibility. Whether this metabolic phenotype of adipose tissue dysfunction,
      which is conducive to fat accretion, plays a role in the induction and
      maintenance of obesity in adolescent girls with PCOS remains to be determined.

PMID- 29220531
TI  - Effect of Age on Response to Therapy and Mortality in Patients With Thyroid
      Cancer at High Risk of Recurrence.
AB  - Context: Age at diagnosis has been identified as a major determinant of thyroid
      cancer-specific survival, with older patients being at higher risk for mortality,
      but the association of age with risk of recurrence has not been studied to date.
      Objective: To examine the effect of a patient's age on response to therapy and
      disease-specific mortality in a cohort of thyroid cancer patients at high risk of
      recurrence, as defined by the American Thyroid Association (ATA) risk
      stratification system. Design: Retrospective cohort study of 320 patients, median
      age 49.3 years, with follicular cell-derived thyroid carcinoma classified at ATA
      high risk and followed for a median of 7 years. Main Outcome Measures:
      Association of age with response to therapy, overall mortality, disease-specific
      mortality, and timing of metastases. Results: Age was a major determinant of
      response to therapy. There was a significantly larger percentage of excellent
      responders among young patients (age <55) than among old patients (age >=55),
      40.3% vs 27.5%, P = 0.002, respectively, whereas the proportion of structural
      incomplete responders was higher in the old group compared with the young group,
      53% vs 33%, P = 0.002, respectively. ATA high-risk young patients with a
      structural incomplete response to therapy had a significantly better disease
      specific survival than old patients (74% vs 12%, P < 0.001, respectively).
      Conclusions: Age was a key predictor of response to therapy and disease-specific
      survival in ATA high-risk thyroid cancer patients. Its incorporation as a
      variable in the ATA risk stratification system would improve its power to predict
      response to therapy as well as mortality.

PMID- 29220532
TI  - Exploring the Predictive Validity of the Susceptibility to Smoking Construct for
      Tobacco Cigarettes, Alternative Tobacco Products, and E-Cigarettes.
AB  - Introduction: Within tobacco prevention programming, it is useful to identify
      youth that are at risk for experimenting with various tobacco products and e
      cigarettes. The susceptibility to smoking construct is a simple method to
      identify never-smoking students that are less committed to remaining smoke-free.
      However, the predictive validity of this construct has not been tested within the
      Canadian context or for the use of other tobacco products and e-cigarettes.
      Methods: This study used a large, longitudinal sample of secondary school
      students that reported never using tobacco cigarettes and non-current use of
      alternative tobacco products or e-cigarettes at baseline in Ontario, Canada. The
      sensitivity, specificity, and positive and negative predictive values of the
      susceptibility construct for predicting tobacco cigarette, e-cigarette, cigarillo
      or little cigar, cigar, hookah, and smokeless tobacco use one and two years after
      baseline measurement were calculated. Results: At baseline, 29.4% of the sample
      was susceptible to future tobacco product or e-cigarette use. The sensitivity of
      the construct ranged from 43.2% (smokeless tobacco) to 59.5% (tobacco
      cigarettes), the specificity ranged from 70.9% (smokeless tobacco) to 75.9%
      (tobacco cigarettes), and the positive predictive value ranged from 2.6%
      (smokeless tobacco) to 32.2% (tobacco cigarettes). Similar values were calculated
      for each measure of the susceptibility construct. Conclusions: A significant
      number of youth that did not currently use tobacco products or e-cigarettes at
      baseline reported using tobacco products and e-cigarettes over a two-year follow
      up period. The predictive validity of the susceptibility construct was high and
      the construct can be used to predict other tobacco product and e-cigarette use
      among youth. Implications: This study presents the predictive validity of the
      susceptibility construct for the use of tobacco cigarettes among secondary school
      students in Ontario, Canada. It also presents a novel use of the susceptibility
      construct for predicting the use of e-cigarettes, cigarillos or little cigars,
      cigars, hookah, and smokeless tobacco among secondary school students in Ontario,
      Canada.

PMID- 29220534
TI  - Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and
      Substance P Levels: A Randomized Sham and Placebo-Controlled Clinical Trial.
AB  - Objective: The aim of this study was to evaluate the effects of acupuncture
      treatment on serum levels of serotonin and substance P (SP) as well as on
      clinical parameters in patients with fibromyalgia (FM). Methods: This is a
      randomized controlled clinical trial. Seventy-five women with FM were randomized
      into one of three kinds of acupuncture treatment: real acupuncture group (AcG),
      sham acupuncture group (ShG), and simulated acupuncture group (SiG). Treatments
      were applied semiweekly for four weeks. The serum levels of serotonin and SP were
      evaluated before and after the eight sessions. Patients were clinically assessed
      by visual analog scale (VAS), the number of tender points (NTP), Fibromyalgia
      Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), and Nottingham
      Health Profile (NHP) at baseline, after the last treatment, and one and three
      months after completion of all treatments. Results: Serum serotonin values
      increased significantly after treatment in AcG and ShG (P < 0.001 and P < 0.01,
      respectively). The increase in the AcG was also different from both of the other
      groups (P < 0.01). While SP levels decreased in the AcG, they increased in the
      SiG (P = 0.001). In the AcG, significant improvements were found in almost all
      clinical outcomes after treatment. These usually continued for three months. In
      the ShG, there were also significant changes on the NTP, VAS, FIQ, and BDI scores
      after treatment. Improvements on the NTP and FIQ scores lasted for three months.
      In the SiG, significant improvements were found only in the NTP, VAS, and BDI
      scores after treatment. Conclusions: Acupuncture, rather than sham or placebo
      acupuncture, may lead to long-term improvements on clinical outcomes and pain
      neuromediator values. Changes in serum serotonin and SP levels may be a valuable
      explanation for acupuncture mechanisms in FM treatment.

PMID- 29220535
TI  - Multiplicity-edited 1 H-1 H TOCSY experiment.
AB  - A 1 H-1 H total correlation spectroscopy (TOCSY) experiment incorporating 13 C
      multiplicity information is proposed. In addition, broadband 1 H homodecoupling
      in the indirect dimension can be implemented using a perfect BIRD module that
      affords exclusive 1 H chemical shift evolution with full decoupling of all
      heteronuclear and homonuclear (including 2 JHH ) coupling constants. As a
      complement to the normal TOCSY and the recent PSYCHE-TOCSY experiments, this
      novel multiplicity-edited TOCSY experiment distinguishes between CH/CH3 (phased
      up) and CH2 (phased down) cross-peaks, which facilitates resonance analysis and
      assignment.

PMID- 29220533
TI  - Androgens, Irregular Menses, and Risk of Diabetes and Coronary Artery
      Calcification in the Diabetes Prevention Program.
AB  - Context: It is unclear whether relative elevations in androgens or irregular
      menses (IM) are associated with greater cardiometabolic risk among women who are
      already overweight and glucose intolerant. Research Design and Methods: We
      conducted a secondary analysis of the Diabetes Prevention Program (DPP) and the
      Diabetes Prevention Program Outcomes Study (DPPOS). Participants included women
      with sex hormone measurements who did not use exogenous estrogen (n = 1422). We
      examined whether free androgen index (FAI) or IM was associated with diabetes
      risk during the DPP/DPPOS or with coronary artery calcification (CAC) at DPPOS
      year 10. Models were adjusted for menopausal status, age, race or ethnicity,
      randomization arm, body mass index (BMI), and hemoglobin A1c. Results: Women had
      an average age of 48.2 +/- 9.9 years. Elevations in FAI and IM were associated
      with greater BMI, waist circumference, and blood pressure and lower adiponectin.
      FAI was not associated with diabetes risk during the DPP/DPPOS [hazard ratio (HR)
      0.97; 95% confidence interval (CI), 0.93 to 1.02] or increased odds of CAC [odds
      ratio (OR) 1.06; 95% CI, 0.92 to 1.23]. IM was also not associated with diabetes
      risk during the DPP/DPPOS (HR 1.07; 95% CI, 0.87 to 1.31) or increased odds of
      CAC (OR 0.89; 95% CI, 0.53 to 1.49). Women who had both relative elevations in
      FAI and IM had similar diabetes risk and odds of CAC as women without these
      conditions. Differences by treatment arm and menopausal status were not observed.
      Conclusions: Among midlife women who were already glucose intolerant and
      overweight, androgen concentrations and IM did not additionally contribute to
      increased risk for diabetes or CAC.

PMID- 29220536
TI  - CD36 deficiency attenuates immune-mediated hepatitis in mice by modulating the
      proapoptotic effects of CXC chemokine ligand 10.
AB  - : The scavenger receptor CD36 recognizes a diverse set of ligands and has been
      implicated in a wide variety of normal and pathological processes, including
      lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular,
      recent findings have demonstrated its crucial functions in sterile inflammation
      and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis
      remains unclear. Concanavalin A (ConA)-induced liver injury is a well-established
      experimental T cell-mediated hepatitis. To understand the role of CD36 in
      hepatitis, we tested the susceptibility of CD36-deficient (CD36-/- ) mice to this
      model, evaluated by a liver enzyme test, terminal deoxynucleotidyl transferase
      dUTP nick-end labeling (TUNEL) assay, histological analysis, mononuclear cell
      (MNC) infiltration, and hepatic proinflammatory factor production. CD36-/- mice
      were less sensitive to ConA-induced hepatitis and had a significantly lower
      number of liver MNCs (LMNCs), including CD4+ cells, CD8+ T cells, natural killer
      cells, natural killer T cells, infiltrating macrophages, and neutrophils, as well
      as reduced expression of inflammatory mediators (tumor necrosis factor alpha, CXC
      chemokine ligand (CXCL) 10, interleukin (IL)-1alpha, monocyte chemotactic protein
      1, and IL-6) compared with controls. Notably, we used bone marrow chimeric mice
      to demonstrate that CD36 expression on nonhematopoietic cells was required to
      drive ConA-induced liver injury. Furthermore, our data show that the CD36
      receptor was essential for CXCL10-induced hepatocyte apoptosis and activation of
      IkappaB kinase, Akt, and Jun N-terminal kinase. Moreover, treatment of wild-type
      mice with genistein, a tyrosine kinase inhibitor that blocks CD36-Lyn signaling,
      attenuated ConA-induced liver injury and reduced the number of MNCs. CONCLUSIONS:
      Our findings suggest that CD36 plays an important proinflammatory role in ConA
      induced liver injury by promoting hepatic inflammation and mediating the
      proapoptotic effect of chemokine CXCL10, and therefore, may be a potential
      therapeutic target for immune-mediated hepatitis. (Hepatology 2018;67:1943-1955).

PMID- 29220538
TI  - Early-stage mycosis fungoides screening investigations: a retrospective analysis
      of 440 cases.

PMID- 29220537
TI  - Milder disease stage in patients with primary biliary cholangitis over a 44-year
      period: A changing natural history.
AB  - : Changes over time in the presenting features and clinical course of patients
      with primary biliary cholangitis are poorly described. We sought to describe
      temporal trends in patient and disease characteristics over a 44-year period
      across a large international primary biliary cholangitis cohort of 4,805 patients
      diagnosed between 1970 and 2014, from 17 centers across Europe and North America.
      Patients were divided into five cohorts according to their year of diagnosis:
      1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n =
      1,815), and >=2010 (n = 235). Age at diagnosis, disease stage, response to
      ursodeoxycholic acid, and clinical outcomes were compared. Mean age at diagnosis
      increased incrementally by 2-3 years per decade from 46.9 +/- 10.1 years in the
      1970s to 57.0 +/- 12.1 years from 2010 onward (P < 0.001). The female to male
      ratio (9:1) and antimitochondrial antibody positivity (90%) were not
      significantly variable. The proportion of patients presenting with mild
      biochemical disease (according to Rotterdam staging) increased from 41.3% in the
      1970s to 72.2% in the 1990s (P < 0.001) and remained relatively stable
      thereafter. Patients with a mild histological stage at diagnosis increased from
      60.4% (1970-1989) to 76.5% (1990-2014) (P < 0.001). Correspondingly, response to
      ursodeoxycholic acid according to Paris-I criteria increased; 51.7% in the 1970s
      and 70.5% in the 1990s (P < 0.001). Recent decades were also characterized by
      lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, P < 0.001)
      and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for
      each respective cohort; P < 0.001). CONCLUSION: In recent decades, a pattern of
      primary biliary cholangitis presentation consistent with an older age at
      diagnosis alongside reduced disease severity has been noted; the observed trends
      may be explained by an increase in routine testing of liver function and/or a
      changing environmental trigger. (Hepatology 2018;67:1920-1930).

PMID- 29220540
TI  - Reflectance confocal microscopy evaluation of trichobacteriosis axilaris.

PMID- 29220539
TI  - Significance and mechanism of androgen receptor overexpression and androgen
      receptor/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma.
AB  - : Hepatocellular carcinoma (HCC) is a male-dominant cancer, and androgen receptor
      (AR) has been linked to the pathogenesis of HCC. However, AR expression and its
      precise role in HCC remain controversial. Moreover, previous antiandrogen and
      anti-AR clinical trials in HCC failed to demonstrate clinical benefits. In this
      study, we found that AR is overexpressed in the nucleus of approximately 37% of
      HCC tumors, which is significantly associated with advanced disease stage and
      poor survival. AR overexpression in HCC cells markedly alters AR-dependent
      transcriptome, stimulates oncogenic growth, and determines therapeutic response
      to enzalutamide, a second generation of AR antagonist. However, AR inhibition
      evokes feedback activation of AKT-mTOR (mechanistic target of rapamycin)
      signaling, a central regulator for cell growth and survival. On the other hand,
      mTOR promotes nuclear AR protein expression by restraining ubiquitin-dependent AR
      degradation and enhancing AR nuclear localization, providing a mechanistic
      explanation for nuclear AR overexpression in HCC. Finally, cotargeting AR and
      mTOR shows significant synergistic anti-HCC activity and decreases tumor burden
      by inducing apoptosis in vivo. CONCLUSION: Nuclear AR overexpression is
      associated with the progression and prognosis of HCC. However, enzalutamide alone
      has limited therapeutic utility attributed to feedback activation of the AKT-mTOR
      pathway. Moreover, mTOR drives nuclear AR overexpression. Cotargeting AR and mTOR
      is a promising therapeutic strategy for HCC. (Hepatology 2018;67:2271-2286).

PMID- 29220541
TI  - Yoga for stroke rehabilitation.
AB  - BACKGROUND: Stroke is a major health issue and cause of long-term disability and
      has a major emotional and socioeconomic impact. There is a need to explore
      options for long-term sustainable interventions that support stroke survivors to
      engage in meaningful activities to address life challenges after stroke.
      Rehabilitation focuses on recovery of function and cognition to the maximum level
      achievable, and may include a wide range of complementary strategies including
      yoga.Yoga is a mind-body practice that originated in India, and which has become
      increasingly widespread in the Western world. Recent evidence highlights the
      positive effects of yoga for people with a range of physical and psychological
      health conditions. A recent non-Cochrane systematic review concluded that yoga
      can be used as self-administered practice in stroke rehabilitation. OBJECTIVES:
      To assess the effectiveness of yoga, as a stroke rehabilitation intervention, on
      recovery of function and quality of life (QoL). SEARCH METHODS: We searched the
      Cochrane Stroke Group Trials Register (last searched July 2017), Cochrane Central
      Register of Controlled Trials (CENTRAL) (last searched July 2017), MEDLINE (to
      July 2017), Embase (to July 2017), CINAHL (to July 2017), AMED (to July 2017),
      PsycINFO (to July 2017), LILACS (to July 2017), SciELO (to July 2017), IndMED (to
      July 2017), OTseeker (to July 2017) and PEDro (to July 2017). We also searched
      four trials registers, and one conference abstracts database. We screened
      reference lists of relevant publications and contacted authors for additional
      information. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      that compared yoga with a waiting-list control or no intervention control in
      stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data from the included studies. We performed all analyses using Review
      Manager (RevMan). One review author entered the data into RevMan; another checked
      the entries. We discussed disagreements with a third review author until
      consensus was reached. We used the Cochrane 'Risk of bias' tool. Where we
      considered studies to be sufficiently similar, we conducted a meta-analysis by
      pooling the appropriate data. For outcomes for which it was inappropriate or
      impossible to pool quantitatively, we conducted a descriptive analysis and
      provided a narrative summary. MAIN RESULTS: We included two RCTs involving 72
      participants. Sixty-nine participants were included in one meta-analysis
      (balance). Both trials assessed QoL, along with secondary outcomes measures
      relating to movement and psychological outcomes; one also measured disability.In
      one study the Stroke Impact Scale was used to measure QoL across six domains, at
      baseline and post-intervention. The effect of yoga on five domains (physical,
      emotion, communication, social participation, stroke recovery) was not
      significant; however, the effect of yoga on the memory domain was significant
      (mean difference (MD) 15.30, 95% confidence interval (CI) 1.29 to 29.31, P =
      0.03), the evidence for this finding was very low grade. In the second study, QoL
      was assessed using the Stroke-Specifc QoL Scale; no significant effect was
      found.Secondary outcomes included movement, strength and endurance, and
      psychological variables, pain, and disability.Balance was measured in both
      studies using the Berg Balance Scale; the effect of intervention was not
      significant (MD 2.38, 95% CI -1.41 to 6.17, P = 0.22). Sensititivy analysis did
      not alter the direction of effect. One study measured balance self-efficacy,
      using the Activities-specific Balance Confidence Scale (MD 10.60, 95% CI -7.08,=
      to 28.28, P = 0.24); the effect of intervention was not significant; the evidence
      for this finding was very low grade.One study measured gait using the Comfortable
      Speed Gait Test (MD 1.32, 95% CI -1.35 to 3.99, P = 0.33), and motor function
      using the Motor Assessment Scale (MD -4.00, 95% CI -12.42 to 4.42, P = 0.35); no
      significant effect was found based on very low-grade evidence.One study measured
      disability using the modified Rankin Scale (mRS) but reported only whether
      participants were independent or dependent. No significant effect was found:
      (odds ratio (OR) 2.08, 95% CI 0.50 to 8.60, P = 0.31); the evidence for this
      finding was very low grade.Anxiety and depression were measured in one study.
      Three measures were used: the Geriatric Depression Scale-Short Form (GCDS15), and
      two forms of State Trait Anxiety Inventory (STAI, Form Y) to measure state
      anxiety (i.e. anxiety experienced in response to stressful situations) and trait
      anxiety (i.e. anxiety associated with chronic psychological disorders). No
      significant effect was found for depression (GDS15, MD -2.10, 95% CI -4.70 to
      0.50, P = 0.11) or for trait anxiety (STAI-Y2, MD -6.70, 95% CI -15.35 to 1.95, P
      = 0.13), based on very low-grade evidence. However, a significant effect was
      found for state anxiety: STAI-Y1 (MD -8.40, 95% CI -16.74 to -0.06, P = 0.05);
      the evidence for this finding was very low grade.No adverse events were
      reported.Quality of the evidenceWe assessed the quality of the evidence using
      GRADE. Overall, the quality of the evidence was very low, due to the small number
      of trials included in the review both of which were judged to be at high risk of
      bias, particularly in relation to incompleteness of data and selective reporting,
      and especially regarding the representative nature of the sample in one study.
      AUTHORS' CONCLUSIONS: Yoga has the potential for being included as part of
      patient-centred stroke rehabilitation. However, this review has identified
      insufficient information to confirm or refute the effectiveness or safety of yoga
      as a stroke rehabilitation treatment. Further large-scale methodologically robust
      trials are required to establish the effectiveness of yoga as a stroke
      rehabilitation treatment.

PMID- 29220542
TI  - Safety and efficacy of apremilast through 104 weeks in patients with moderate to
      severe psoriasis who continued on apremilast or switched from etanercept
      treatment: findings from the LIBERATE study.
AB  - BACKGROUND: Apremilast, an oral phosphodiesterase-4 inhibitor, has demonstrated
      efficacy in patients with moderate to severe psoriasis. OBJECTIVE: To evaluate
      long-term efficacy and safety of apremilast in biologic-naive patients with
      moderate to severe plaque psoriasis and safety of switching from etanercept to
      apremilast in the phase 3b LIBERATE trial. METHODS: Two hundred fifty patients
      were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through
      Week 16; thereafter, all patients continued or switched to apremilast through
      Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and
      104 were assessed using the Psoriasis Area and Severity Index (PASI; 0-72), Scalp
      Physician Global Assessment (ScPGA; 0-5) and Nail Psoriasis Severity Index
      (NAPSI; 0-8); patient-reported outcomes (PROs) were assessed using the
      Dermatology Life Quality Index (DLQI; 0-32) and pruritus visual analog scale
      (VAS; 0-100 mm). RESULTS: The apremilast-extension phase (Weeks 16-104) included
      226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74)
      and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and
      51.9% of these patients, respectively, maintained >=75% reduction from baseline
      in PASI score (based on last-observation-carried-forward analysis). Across
      treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%-59.2% of
      patients; NAPSI mean change from baseline was -48.1% to -51.1%; DLQI score <=5
      was achieved by 66.0%-72.5% of patients; and pruritus VAS mean change from
      baseline was -24.4 to -32.3. AEs in >=5% of patients (diarrhoea, nausea,
      nasopharyngitis, upper respiratory tract infection and headache) did not increase
      with prolonged apremilast exposure. CONCLUSIONS: Apremilast demonstrated
      significant and sustained improvements in skin, scalp, nails and PROs (pruritus
      and quality of life) over 104 weeks in patients with moderate to severe plaque
      psoriasis. Safety was consistent with the known safety profile of apremilast.

PMID- 29220543
TI  - Skin cancer prevention campaign in childhood: survey based on 3676 children in
      Brazil.
AB  - BACKGROUND AND OBJECTIVES: Primary skin cancer prevention campaigns are essential
      and more effective among children, not only because of the importance of sun
      exposure effects during this period, but also because this age is when
      individuals are developing behaviours. The Brazilian Society of Dermatology -
      Regional State of Sao Paulo developed and conducted the programme named 'The Sun,
      Friend of Childhood', a school health education and disease prevention project
      for children and parents. Our objective was to evaluate the cognitive and
      behavioural effects of the children and parents before and after an education
      model-based intervention of sun protection. METHODS: We carried out a study on a
      school population of Social Service of Industry - Regional State of Sao Paulo,
      from the first to the fifth years of the regular course (6-10 years). Our
      educational project was planned to be based on two children's learning tools
      (comic magazine and a DVD cartoon). Questionnaires in relation to habits and
      knowledge in sun exposure were applied to the children (3776) before and (2748)
      after the intervention. A questionnaire was applied to 3663 parents regarding
      personal details and habits of their children. RESULTS: According to the
      McNemar's statistical test, all changes in the children in acquiring new
      knowledge about good practices for sun exposure were statistically significant.
      CONCLUSIONS: Educative sun exposure programmes in childhood are a relevant tool
      to modify the history of life for next generations, to concern the skin cancer
      and good health practices.

PMID- 29220544
TI  - Antihypertensive drug treatment: the real-life challenge.

PMID- 29220545
TI  - Effects of the Bidentate Ligand on the Photophysical Properties, Cellular Uptake,
      and (Photo)cytotoxicity of Glycoconjugates Based on the [Ru(tpy)(NN)(L)]2+
      Scaffold.
AB  - Ruthenium polypyridyl complexes have received widespread attention as potential
      chemotherapeutics in photodynamic therapy (PDT) and in photochemotherapy (PACT).
      Here, we investigate a series of sixteen ruthenium polypyridyl complexes with
      general formula [Ru(tpy)(N-N)(L)]+/2+ (tpy=2,2':6',2''-terpyridine, N-N=bpy (2,2'
      bipyridine), phen (1,10-phenanthroline), dpq (pyrazino[2,3
      f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2',3'-c]phenazine, dppn
      (benzo[i]dipyrido[3,2-a:2',3'-c]phenazine), pmip (2-(4-methylphenyl)-1H
      imidazo[4,5-f][1,10]phenanthroline), pymi ((E)-N-phenyl-1-(pyridin-2
      yl)methanimine), or azpy (2-(phenylazo)pyridine), L=Cl- or 2-(2-(2
      (methylthio)ethoxy)ethoxy)ethyl-beta-d-glucopyranoside) and their potential for
      either PDT or PACT. We demonstrate that although increased lipophilicity is
      generally related to increased uptake of these complexes, it does not necessarily
      lead to increased (photo)cytotoxicity. However, the non-toxic complexes are
      excellent candidates as PACT carriers.

PMID- 29220546
TI  - Differential coordination of stomatal conductance, mesophyll conductance, and
      leaf hydraulic conductance in response to changing light across species.
AB  - Stomatal conductance (gs ) and mesophyll conductance (gm ) represent major
      constraints to photosynthetic rate (A), and these traits are expected to
      coordinate with leaf hydraulic conductance (Kleaf ) across species, under both
      steady-state and dynamic conditions. However, empirical information about their
      coordination is scarce. In this study, Kleaf , gas exchange, stomatal kinetics,
      and leaf anatomy in 10 species including ferns, gymnosperms, and angiosperms were
      investigated to elucidate the correlation of H2 O and CO2 diffusion inside leaves
      under varying light conditions. Gas exchange, Kleaf , and anatomical traits
      varied widely across species. Under light-saturated conditions, the A, gs , gm ,
      and Kleaf were strongly correlated across species. However, the response patterns
      of A, gs , gm , and Kleaf to varying light intensities were highly species
      dependent. Moreover, stomatal opening upon light exposure of dark-adapted leaves
      in the studied ferns and gymnosperms was generally faster than in the
      angiosperms; however, stomatal closing in light-adapted leaves after darkening
      was faster in angiosperms. The present results show that there is a large
      variability in the coordination of leaf hydraulic and gas exchange parameters
      across terrestrial plant species, as well as in their responses to changing
      light.

PMID- 29220548
TI  - Haem oxygenase: A functionally diverse enzyme of photosynthetic organisms and its
      role in phytochrome chromophore biosynthesis, cellular signalling and defence
      mechanisms.
AB  - Haem oxygenase (HO) is a universal enzyme that catalyses stereospecific cleavage
      of haem to BV IX alpha and liberates Fe+2 ion and CO as by-product. Beside haem
      degradation, it has important functions in plants that include cellular defence,
      stomatal regulation, iron mobilization, phytochrome chromophore synthesis, and
      lateral root formation. Phytochromes are an extended family of photoreceptors
      with a molecular mass of 250 kDa and occur as a dimer made up of 2 equivalent
      subunits of 125 kDa each. Each subunit is made of two components: the
      chromophore, a light-capturing pigment molecule and the apoprotein. Biosynthesis
      of phytochrome (phy) chromophore includes the oxidative splitting of haem to
      biliverdin IX by an enzyme HO, which is the decisive step in the biosynthesis. In
      photosynthetic organisms, BValpha is reduced to 3Z PPhiB by a ferredoxin
      dependent PPhiB synthase that finally isomerised to PPhiB. The synthesized PPhiB
      assembles with the phytochrome apoprotein in the cytoplasm to generate
      holophytochrome. Thus, necessary for photomorphogenesis in plants, which has
      confirmed from the genetic studies, conducted on Arabidopsis thaliana and pea.
      Besides the phytochrome chromophore synthesis, the review also emphasises on the
      current advances conducted in plant HO implying its developmental and defensive
      role.

PMID- 29220547
TI  - Impact of Moderate Alcohol Discontinuation on Insulin Action and Secretion in
      Latinos With and Without Hepatitis C.
AB  - BACKGROUND: Insulin resistance (IR) is associated with hepatitis C virus (HCV),
      and Latinos are both at risk of IR and are disproportionately affected by HCV.
      Moderate alcohol consumption improves insulin sensitivity and may modify HCV
      associated IR. We investigated the impact of moderate alcohol discontinuation on
      insulin sensitivity and secretion in Latinos using direct measurements. METHODS:
      Twenty-five nondiabetic, noncirrhotic Latino adults without (n = 17) or with (n =
      8) HCV underwent 3-day metabolic assessment before and after prescription of 6
      weeks of moderate alcohol discontinuation. Peripheral IR was measured via steady
      state plasma glucose (SSPG) and hepatic IR using endogenous glucose production
      during a 2-step 240-minute insulin suppression test. Insulin secretion was
      measured using graded glucose infusion test. RESULTS: Baseline mean age was 46 +/
      11 years, 63% male, 29% had HCV, and mean body mass index was 27 +/- 4 kg/m2 .
      Compared to non-HCV, HCV patients had a higher median SSPG (132 vs. 98.8 mg/dl, p
      = 1.0), hepatic IR (13.5 vs. 11.3, p = 0.24), and insulin secretion rate (ISR
      AUC, 1,290 vs. 1,250 pmol/min, p = 0.98). After confirmed alcohol
      discontinuation, hepatic IR was the only parameter that changed significantly
      (increased, mean change 2.6 +/- 4.8, p = 0.02). Higher baseline alanine
      aminotransferase (ALT) was also associated with a greater change in hepatic IR
      (average 4.0 points/ALT doubling, p = 0.004), and HCV was associated with a
      lesser change (average -7.3 points, p = 0.002), independent of ALT. CONCLUSIONS:
      Short-term moderate alcohol discontinuation adversely impacted hepatic IR in
      Latinos which was influenced by level of ALT at baseline independent of etiology.
      Although reduction in ALT through weight loss and HCV eradication remains a
      priority in improving IR, the observed nonharmful effect of moderate alcohol use
      represents a potentially confounding variable that warrants further study.

PMID- 29220549
TI  - Seasonality of cavitation and frost fatigue in Acer mono Maxim.
AB  - Although cavitation is common in plants, it is unknown whether the cavitation
      resistance of xylem is seasonally constant or variable. We tested the changes in
      cavitation resistance of Acer mono before and after a controlled cavitation
      refilling and freeze-thaw cycles for a whole year. Cavitation resistance was
      determined from 'vulnerability curves' showing the percent loss of conductivity
      versus xylem tension. Cavitation fatigue was defined as a reduction of cavitation
      resistance following a cavitation-refilling cycle, whereas frost fatigue was
      caused by a freeze-thaw cycle. A. mono developed seasonal changes in native
      embolisms; values were relatively high during winter but relatively low and
      constant throughout the growing season. Cavitation fatigue occurred and changed
      seasonally during the 12-month cycle; the greatest fatigue response occurred
      during summer and the weakest during winter, and the transitions occurred during
      spring and autumn. A. mono was highly resistant to frost damage during the
      relatively mild winter months; however, a quite different situation occurred
      during the growing season, as the seasonal trend of frost fatigue was strikingly
      similar to that of cavitation fatigue. Seasonality changes in cavitation
      resistance may be caused by seasonal changes in the mechanical properties of the
      pit membranes.

PMID- 29220550
TI  - Breaking Kuhn's paradigm in advanced hepatocellular carcinoma.

PMID- 29220552
TI  - PPAPI: A Program for Groundwater Modeling Tasks in Distributed Parallel Computing
      Environments.

PMID- 29220551
TI  - Consensus on the management of patients with psoriatic arthritis in a dermatology
      setting.
AB  - BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease
      associated with psoriasis (PsO). Early diagnosis and prompt therapeutic
      intervention are crucial for limiting PsA progression and prevention of
      disability. Dermatologists are in a privileged position to detect early PsA. The
      management of patients with PsA in the dermatology setting is widely variable.
      OBJECTIVE: To provide practical recommendations for the management of patients
      with PsA in the dermatology setting including early diagnosis and treatment.
      METHODS: A consensus document was written by an expert panel composed by
      dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant
      questions were selected and elaborated with answers/statements based on a
      narrative literature review. The resulting document was discussed in a face-to
      face meeting adopting a nominal group technique to reach consensus (i.e. 100%
      agreement) using the Delphi method. RESULTS: A consensus was achieved in defining
      the following: the clinical characteristics differentiating inflammatory and non
      inflammatory signs and symptoms of joint disease; the most important differential
      diagnoses of PsA in clinical practice; the most useful screening questionnaires,
      serum laboratory tests and imaging techniques for the detection of early PsA; the
      criteria for dermatologist to refer patients with PsO to rheumatologist; the
      criteria for the diagnosis of PsA; the selection of the indices that the
      dermatologist could use for measuring the activity and severity of PsA in
      clinical practice; when systemic steroids and/or intra-articular steroid
      injections are indicated in the treatment of PsA. Finally, systemic treatments
      including synthetic and biologic disease-modifying antirheumatic drugs to be
      considered for the treatment of PsA have been reported. CONCLUSIONS: The
      implementations of these practical recommendations could be very helpful for the
      management of patients with PsA in the dermatology setting including early
      diagnosis and treatment.

PMID- 29220553
TI  - Isomeric Column-Forming Esters and Imides with Varying Curvatures of the Aromatic
      Plane.
AB  - Dibenzo[a,j]coronene-tetracarboxylic alkyl esters and imides with either a
      centrosymmetric bis-peri substitution pattern or a polar bis-ortho substitution
      pattern form hexagonal columnar mesophases, which in the case of the imides
      persist at room temperature. The bis-peri isomers are obtained via a two-fold
      oxidative photocyclization; the bis-ortho isomers are accessed via a glyoxylic
      Perkin reaction of triphenylene and naphthalene building blocks. Steric
      congestion between the substituents and the adjacent benzo protrusion in the bis
      ortho esters and imides leads to bending of the aromatic plane, which thus avoids
      twisting. These isomers surprisingly show a more pronounced liquid crystalline
      behaviour than their non-bent bis-peri homologs, accommodating non-planarity with
      columnar order by slipped stacking. Whereas both types of ester and the bis-peri
      imide show an optical behaviour typical for perylene chromophores, the strongly
      bent bis-ortho imide distinguishes itself notably from them by its absorption
      spectrum. The electron acceptor strength of the isomeric diimides is found to
      differ, the hexagonal (peri) diimide having a 0.20 eV lower LUMO energy than the
      pentagonal (ortho) isomer.

PMID- 29220554
TI  - Assessment of dietary sodium intake using a food frequency questionnaire and 24
      hour urinary sodium excretion: a systematic literature review.
AB  - Food frequency questionnaires (FFQs) are often used to assess dietary sodium
      intake, although 24-hour urinary excretion is the most accurate measure of
      intake. The authors conducted a systematic review to investigate whether FFQs are
      a reliable and valid way of measuring usual dietary sodium intake. Results from
      18 studies are described in this review, including 16 validation studies. The
      methods of study design and analysis varied widely with respect to FFQ
      instrument, number of 24-hour urine collections collected per participant,
      methods used to assess completeness of urine collections, and statistical
      analysis. Overall, there was poor agreement between estimates from FFQ and 24
      hour urine. The authors suggest a framework for validation and reporting based on
      a consensus statement (2004), and recommend that all FFQs used to estimate
      dietary sodium intake undergo validation against multiple 24-hour urine
      collections.

PMID- 29220555
TI  - Multiparameter cytometric analysis of complex cellular response.
AB  - Complex analysis of cellular responses after experimental treatment is important
      for screening, mechanistic understanding of treatment effects, and the
      identification of sensitive and resistant cell phenotypes. Modern multicolor flow
      cytometry has demonstrated its power for such analyses. Here, we introduce a
      multiparametric protocol for complex analysis of cytokinetics by the simultaneous
      detection of seven fluorescence parameters. This analysis includes the detection
      of two surface markers for immunophenotyping, analysis of proliferation based on
      the cell cycle and the measurement of incorporated nucleoside analogue 5-ethynyl
      2'-deoxyuridine (EdU) in newly synthesized DNA, analysis of DNA damage using an
      anti-phospho-histone H2A.X (Ser139) antibody, and determination of cell death
      using a fixable viability probe and intracellular detection of caspase-3
      activation. To demonstrate the applicability of this protocol for the analysis of
      heterogeneous and complex cell responses, we used different treatments and model
      cell lines. We demonstrated that this protocol has the potential to provide
      complex and simultaneous analysis of cytokinetics and analyze the heterogeneity
      of the response at the single-cell level. (c) 2017 International Society for
      Advancement of Cytometry.

PMID- 29220556
TI  - Drug treatment of hypertension in Sweden in relation to sex, age, and
      comorbidity.
AB  - The authors investigated antihypertensive drug treatment in Sweden using the
      Stockholm Regional Healthcare Data Warehouse, providing information on all
      healthcare consultations, diagnoses, hospitalizations, dispensed prescription
      drugs, sex, and age in 2.1 million persons. This cross-sectional analysis
      identified 292 428 individuals 20 years or older with hypertension (mean age 68
      +/- 13 years, 53% women). About half had no diabetes mellitus or cardiovascular
      comorbidity. The number of dispensed drugs was lower in women than in men (1.9 +/
      1.3 vs 2.1 +/- 1.5, P < .001). Women more often used diuretics, angiotensin
      receptor blockers, and beta-blockers, while men used more angiotensin-converting
      enzyme inhibitors and calcium channel blockers (all P < .01). In women, 66% with
      diabetes mellitus and 72% with heart failure used angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers vs 76% and 79% in men (all P < .001,
      adjusted for age and comorbidity). Thus, sex differences in treatment prevail.
      There is room for improvement, which could reduce cardiovascular complications.

PMID- 29220558
TI  - ?

PMID- 29220557
TI  - ?

PMID- 29220559
TI  - ?

PMID- 29220560
TI  - ?

PMID- 29220561
TI  - ?

PMID- 29220562
TI  - ?

PMID- 29220563
TI  - ?

PMID- 29220564
TI  - ?

PMID- 29220565
TI  - ?

PMID- 29220566
TI  - ?

PMID- 29220567
TI  - Structural Basis of Histone Demethylase KDM6B Histone 3 Lysine 27 Specificity.
AB  - KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyze demethylation of di
      and trimethylated lysine on histone 3 lysine 27 (H3K27me3/2) and play an
      important role in repression of developmental genes. Despite identical amino acid
      sequence in the immediate surroundings of H3K9me3/2 (ARKS), the enzymes do not
      catalyze demethylation of this general marker of repression. To address this
      question for KDM6B, we used computational methods to identify H3(17-33)-derived
      peptides with improved binding affinity that would allow co-crystallization with
      the catalytic core of human KDM6B (ccKDM6B). A total of five peptides were
      identified, and their IC50 values were determined in a matrix-assisted laser
      desorption ionization time-of-flight-based assay. Despite none of the peptides
      showing affinity significantly higher than that of the H3(17-33) peptide, it was
      possible to co-crystallize ccKDM6B with a H3(17-33)A21M peptide. This structure
      reveals the interactions between the KDM6B zinc binding domain and the H3(17-23)
      region. Although KDM6A and KDM6B differ in primary sequence, particularly in the
      H3L20 binding pocket of the zinc binding domains, where two histidines in KDM6A
      have been replaced by a glutamate and a tyrosine, they bind H3(17-23) in a very
      similar fashion. This structure shows that KDM6B, in analogy with KDM6A, also
      uses the zinc binding domain to achieve H3K27me3/me2 specificity. The histidine
      to glutamine substitution at amino acid position 1564 in the KDM6B zinc binding
      domain can further explain why KDM6B binds substrates with an affinity higher
      than that of KDM6A.

PMID- 29220568
TI  - Aniline-Based Inhibitors of Influenza H1N1 Virus Acting on Hemagglutinin-Mediated
      Fusion.
AB  - Two series of easily accessible anilines were identified as inhibitors of
      influenza A virus subtype H1N1, and extensive chemical synthesis and analysis of
      the structure-activity relationship were performed. The compounds were shown to
      interfere with low pH-induced membrane fusion mediated by the H1 and H5 (group 1)
      hemagglutinin (HA) subtypes. A combination of virus resistance, HA interaction,
      and molecular dynamics simulation studies elucidated the binding site of these
      aniline-based influenza fusion inhibitors, which significantly overlaps with the
      pocket occupied by some H3 HA-specific inhibitors, indicating the high relevance
      of this cavity for drug design.

PMID- 29220569
TI  - Crocadepsins-Depsipeptides from the Myxobacterium Chondromyces crocatus Found by
      a Genome Mining Approach.
AB  - Analysis of the genome sequence of the myxobacterium Chondromyces crocatus Cm c5
      revealed the presence of numerous cryptic megasynthetase gene clusters, one of
      which we here assign to two previously unknown chlorinated metabolites by a
      comparative gene inactivation and secondary metabolomics approach. Structure
      elucidation of these compounds revealed a unique cyclic depsipeptide skeleton
      featuring beta- and delta-amide bonds of aspartic acid and 3-methyl ornithine
      moieties, respectively. Insights into their biosynthesis were obtained by
      targeted gene inactivation and feeding experiments employing isotope-labeled
      precursors. The compounds were produced ubiquitously by the species Chondromyces
      crocatus and were found to inhibit the carbon storage regulator-RNA interaction.

PMID- 29220570
TI  - Neuromicrobiology: How Microbes Influence the Brain.
AB  - We review here recent discoveries in the exciting new field of neuromicrobiology.
      This field encompasses the interactions between the microbiome and the central
      nervous system. The microbiome has a tremendous impact on human health. In
      particular, the gut microbiota may play a key role in many essential processes in
      health and disease via the activity of the gut-brain axis, possibly contributing
      to autism spectrum disorders, Alzheimer's disease, Parkinson's disease,
      depression, and anxiety disorder. Gut microbes may also be involved in
      nociception, complex host behaviors, and brain development. Future efforts will
      be needed to determine whether the observed associations correspond to causative
      mechanisms, as well as to engineer effective interventions to modulate the
      effects of the microbiome on the central nervous system.

PMID- 29220571
TI  - Fluorescent Liquid Metal As a Transformable Biomimetic Chameleon.
AB  - Liquid metal (LM) is of core interest for a wide variety of newly emerging areas.
      However, the functional materials thus made so far by LM only could display a
      single silver-white appearance. In this study, colorful LM marbles working like a
      transformable biomimetic robot were proposed for the first time and fabricated
      from LM droplets through encasing them with fluorescent nanoparticles. We
      demonstrated that this unique LM marble can be manipulated into various stable
      magnificent appearances as one desires and then split and merge among different
      colors. Such multifunctional LM is capable of responding to the outside electric
      stimulus and realizing shape transformation and discoloration behaviors as well.
      Furthermore, the electric stimuli has been successfully introduced to trigger the
      release of nano/microparticles from the LM, and the mechanism lying behind was
      clarified. The present fluorescent LM was expected to offer important
      opportunities for diverse applications, especially in a wide range of functional
      smart material areas.

PMID- 29220572
TI  - Martian Redox Chemistry: Oxygen Reduction in Low-Temperature Magnesium
      Perchlorate Brines.
AB  - NASA has a mandate to send humans to Mars by 2033. Recent discoveries regarding
      Mars include the likely presence of low-temperature liquid brines on the planet's
      surface. This work investigates redox chemistry in near saturated aqueous 2.8 M
      Mg(ClO4)2 at temperatures as low as -34  degrees C. These conditions are
      comparable to those thought to be found on the Martian surface. In particular,
      electro-reduction of oxygen is studied, and the diffusion coefficient and
      solubility of this important redox species are established.

PMID- 29220573
TI  - The Mayonnaise Effect.
AB  - Structuring caused by the mixing of liquids or the addition of solutes to a
      solvent causes the viscosity to increase. The classical example is mayonnaise: a
      mixture of two low-viscosity liquids, water and oil, is structured through the
      addition of a surfactant creating a dispersed phase, causing the viscosity to
      increase a thousand-fold. The dramatic increase in viscosity in highly
      concentrated solutions is a long-standing unsolved problem in physical chemistry.
      Here we will show that this viscosity increase can be understood in terms of the
      solute-induced structuring of the first solvation shell, leading to a jamming
      transition at a critical concentration. As the jamming transition is approached,
      the viscosity naturally increases according to a Vogel-Fulcher-Tammann type
      expression. This result calls into question the validity of the Jones-Dole B
      coefficient as an indicator of the structure making or breaking ability of
      solutes.

PMID- 29220579
TI  - Pupillary Responses to Static Images of Men and Women: A Possible Measure of
      Sexual Interest?
AB  - The pupil dilates to images that are arousing. In Experiment 1, we examined if
      the pupil's response to brief presentations (2,000 ms) of static images could be
      used to identify individuals' sexual orientation. Participants were grouped
      according to their self-reported gender and sexual orientation (male
      heterosexual, N = 20; male bisexual, N = 13; male homosexual, N = 19; female
      heterosexual, N = 28; female bisexual, N = 21; female homosexual, N = 17). Pupil
      size was monitored to images of men in seminude poses, women in seminude poses,
      or neutral images. Every group showed the same pattern of responses, with the
      greatest dilation to male images, then female images, and least dilation to the
      neutral images. Experiment 2 used more tightly controlled stimuli and tested at
      two different image durations (150 and 3,000 ms). Both heterosexual men (N = 18)
      and women (N = 20) showed greater pupil dilation to images of nude men than to
      nude women. However, in Experiment 3, where we reduced the erotic content by
      using images of clothed models, both heterosexual men and women showed greater
      pupil dilation to images of women. The results showed that while the pupil does
      dilate strongly to sexual imagery, its response to these brief static images does
      not correspond to a person's sexual orientation in a simple manner.

PMID- 29220577
TI  - From Solvent-Free to Dilute Electrolytes: Essential Components for a Continuum
      Theory.
AB  - The increasing number of experimental observations on highly concentrated
      electrolytes and ionic liquids show qualitative features that are distinct from
      dilute or moderately concentrated electrolytes, such as self-assembly, multiple
      time relaxation, and underscreening, which all impact the emergence of
      fluid/solid interfaces, and the transport in these systems. Because these
      phenomena are not captured by existing mean-field models of electrolytes, there
      is a paramount need for a continuum framework for highly concentrated
      electrolytes and ionic liquid mixtures. In this work, we present a self
      consistent spatiotemporal framework for a ternary composition that comprises ions
      and solvent employing a free energy that consists of short- and long-range
      interactions, along with an energy dissipation mechanism obtained by Onsager's
      relations. We show that the model can describe multiple bulk and interfacial
      morphologies at steady-state. Thus, the dynamic processes in the emergence of
      distinct morphologies become equally as important as the interactions that are
      specified by the free energy. The model equations not only provide insights into
      transport mechanisms beyond the Stokes-Einstein-Smoluchowski relations but also
      enable qualitative recovery of three distinct regions in the full range of the
      nonmonotonic electrical screening length that has been recently observed in
      experiments in which organic solvent is used to dilute ionic liquids.

PMID- 29220582
TI  - Accounting for Men's Refusal of Heterosex: A Story-Completion Study with Young
      Adults.
AB  - In the present study we bring together theory regarding the construction of
      heterosexuality and masculinities to understand the shifting and changing terrain
      of heterosexual sex (heterosex). We use inductive qualitative content analysis of
      story completion data to discover the different ways that heterosex is
      constructed by the male and female respondents in scenarios where women initiate
      sex and men, at first, refuse. The stories represented a spectrum of responses
      that reify and subvert dominant understandings of heterosex. Five major themes
      were generated from the current data (1) men should initiate sex, (2) he wants to
      take it slowly, (3) it is natural for men to want sex, (4) it is men's job to
      look after women, and (5) coercion. We discuss in detail the dominant narratives
      described by women and men and how they may be shifting. The study thus provides
      a rich, experience-based representation of heterosexual sexual activity and
      suggests subtle shifts in how masculinity is managed within heterosexual
      relationships.

PMID- 29220575
TI  - Dual-Gated Microparticles for Switchable Antibody Release.
AB  - We pioneer the design of dual-gated microparticles, both responsive to changes in
      temperature and pH, for stimuli-responsive chromatography targeted at the
      efficient separation of antibodies. Dual-gated microspheres were synthesized by
      introducing RAFT-based thiol-terminal block copolymers of poly(N
      isopropylacrylamide-b-4-vinylpyridine) (P(NIPAM-b-4VP, 4800 <= Mn/Da <= 10 000,
      featuring block length ratios of 29:7, 29:15, and 29:30, respectively) by thiol
      epoxy driven ligation to the surface of poly(glycidyl methacrylate) (PGMA)
      microparticles (10-12 MUm), whereby the 4-vinylpyridine units within the lateral
      chain enable protein binding. The switchable protein release abilities of the
      resulting microparticle resins are demonstrated by adsorption of immunoglobulins
      at 40  degrees C and pH 8 and their release at 5  degrees C or pH 3,
      respectively. We demonstrate that P(NIPAM29-b-4VP30)-grafted PGMA particles show
      a maximum adsorption capacity for immunoglobulins of 18.9 mg mL-1 settled resin
      at 40  degrees C/pH 8, whereas the adsorption capacity decreased to 7.5 mg mL-1
      settled resin at 5  degrees C while retaining the pH value, allowing the
      unloading of the chromatographic column by a facile temperature switch.
      Critically, regeneration of the dual-gated microspheres became possible by
      lowering the pH to 3.

PMID- 29220578
TI  - PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human
      Mesenchymal Stem Cells in Humanized Mice.
AB  - Pulmonary fibrosis is a chronic progressive lung disease with few treatments.
      Human mesenchymal stem cells (MSCs) have been shown to be beneficial in pulmonary
      fibrosis because they have immunomodulatory capacity. However, there is no
      reliable model to test the therapeutic effect of human MSCs in vivo. To mimic
      pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary
      fibrosis model in humanized mice. With this model, the benefit of human MSCs in
      pulmonary fibrosis and the underlying mechanisms were investigated. In addition,
      the relevant parameters in patients with pulmonary fibrosis were examined. We
      demonstrate that human CD8+ T cells were critical for the induction of pulmonary
      fibrosis in humanized mice. Human MSCs could alleviate pulmonary fibrosis and
      improve lung function by suppressing bleomycin-induced human T-cell infiltration
      and proinflammatory cytokine production in the lungs of humanized mice.
      Importantly, alleviation of pulmonary fibrosis by human MSCs was mediated by the
      PD-1/programmed death-ligand 1 pathway. Moreover, abnormal PD-1 expression was
      found in circulating T cells and lung tissues of patients with pulmonary
      fibrosis. Our study supports the potential benefit of targeting the PD
      1/programmed death-ligand 1 pathway in the treatment of pulmonary fibrosis.

PMID- 29220583
TI  - Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in
      Metastatic Cancer Patients: A Retrospective Study.
AB  - BACKGROUND: Serum vitamin B12 levels have been proposed as one of the survival
      prediction factors, although no survival analysis in metastatic cancer patients
      has been conducted yet. This study examined whether serum vitamin B12 levels
      could be a prognostic factor in metastatic cancer patients. METHODS: Data from a
      retrospective chart review were used to perform Kaplan-Meier and multivariate
      analyses of the Cox proportional hazards. Subgroup analysis was performed on
      patients without a liver lesion (hepatocellular carcinoma or liver metastasis).
      RESULTS: A total of 523 patients were included. The median survival time was 1.8
      months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group
      (211-911 pg/mL) (p < 0.001). In patients without a liver lesion, the median
      survival times were 2.1 and 6.1 mo in the high and normal B12 groups,
      respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12
      level was an independent prognostic factor for overall survival (hazard ratio
      [HR]: 1.62; 95% confidence interval [CI]: 1.34-1.96, p < 0.001). CONCLUSION:
      Serum vitamin B12 level can be used to predict survival time in metastatic cancer
      patients. Further large-scale cohort studies are required to confirm these
      findings.

PMID- 29220574
TI  - Nanoplasmonic Alloy of Au/Ag Nanocomposites on Paper Substrate for Biosensing
      Applications.
AB  - Plasmonic alloy has attracted much interest in tailoring localized surface
      plasmon resonance (LSPR) for recent biosensing techniques. In particular, paper
      based plasmonic substrates allow capillary-driven lateral flow as well as three
      dimensional metal nanostructures, and therefore they become actively transferred
      to LSPR-based biosensing such as surface-enhanced Raman spectroscopy (SERS) or
      metal-enhanced fluorescence (MEF). However, employing plasmonic alloy nanoislands
      on heat-sensitive substrate is still challenging, which significantly inhibits
      broad-range tailoring of the plasmon resonance wavelength (PRW) for superior
      sensitivity. Here we report paper-based plasmonic substrate with plasmonic alloy
      of Au/Ag nanocomposites for highly sensitive MEF and SERS biosensing
      applications. The nanofabrication procedures include concurrent deposition of Au
      and Ag below 100  degrees C without any damage on cellulose fibers. The Au/Ag
      nanocomposites feature nanoplasmonic alloy with single plasmon peak as well as
      broad-range tunability of PRW by composition control. This paper-based plasmonic
      alloy substrate enables about twofold enhancement of fluorescence signals and
      selective MEF after paper chromatography. The experimental results clearly
      demonstrate extraordinary enhancement in SERS signals for picomolar detection of
      folic acid as a cancer biomarker. This new method provides huge opportunities for
      fabricating plasmonic alloy on heat-sensitive substrate and biosensing
      applications.

PMID- 29220576
TI  - Oxygenic Hybrid Semiconducting Nanoparticles for Enhanced Photodynamic Therapy.
AB  - Photodynamic nanotheranostics has shown great promise for cancer therapy;
      however, its therapeutic efficacy is limited due to the hypoxia of tumor
      microenvironment and the unfavorable bioavailability of existing photodynamic
      agents. We herein develop hybrid core-shell semiconducting nanoparticles (SPN-Ms)
      that can undergo O2 evolution in hypoxic solid tumor to promote photodynamic
      process. Such oxygenic nanoparticles are synthesized through a one-pot surface
      growth reaction and have a unique multilayer structure cored and coated with
      semiconducting polymer nanoparticles (SPNs) and manganese dioxide (MnO2)
      nanosheets, respectively. The SPN core serves as both NIR fluorescence imaging
      and photodynamic agent, while the MnO2 nanosheets act as a sacrificing component
      to convert H2O2 to O2 under hypoxic and acidic tumor microenvironment. As
      compared with the uncoated SPN (SPN-0), the oxygenic nanoparticles (SPN-M1)
      generate 2.68-fold more 1O2 at hypoxic and acidic conditions under NIR laser
      irradiation at 808 nm. Because of such an oxygen-evolution property, SPN-M1 can
      effectively eradicate cancer cells both in vitro and in vivo. Our study thus not
      only reports an in situ synthetic method to coat organic nanoparticles but also
      develops a tumor-microenvironment-sensitive theranostic nanoagent to overcome
      hypoxia for amplified therapy.

PMID- 29220587
TI  - FTO Gene Affects Obesity and Breast Cancer Through Similar Mechanisms: A New
      Insight into the Molecular Therapeutic Targets.
AB  - OBJECTIVES: This review focused on the possible mediatory role of the FTO in the
      association between obesity and breast cancer. METHOD: All articles published in
      English from June 1990 to January 2017 were studied. The search terms used were
      FTO gene, FTO polymorphism, breast cancer, and obesity. Inclusion criteria
      consisted of assessment of the relationship between FTO polymorphisms and/or FTO
      expression level with obesity and/or breast cancer as a primary outcome. RESULTS:
      The FTO gene may have a role in the cellular sensing of macronutrients. Over
      expression of the FTO gene increases the levels of mammalian target of rapamycin
      (mTOR) signaling that is a key regulator of cell growth. Moreover, some SNPs in
      intron locations of the FTO gene exert their effects on body mass index, body
      composition and breast cancer risk through change of the homeobox transcription
      factor iriquois 3 (IRX3) gene expression level. CONCLUSION: The FTO gene may has
      a critical role in obesity and breast cancer. Similar molecular mechanisms may
      play a role in the development of breast cancer and obesity. If this result is
      correct then, it will be interesting to examine the FTO gene as a molecular
      therapeutics target.

PMID- 29220586
TI  - Co-Occurring Psychosocial Problems and Multiple Sexual Partners among Men Who
      Have Sex with Men in Shanghai, China: A Syndemic Approach.
AB  - We aimed to apply syndemic theory to verify the association and reinforcing
      effects between psychosocial problems and multiple sexual partners (MSP) of men
      who have sex with men (MSM) in Shanghai, China. A cross-sectional study was
      conducted among 547 MSM in Shanghai, China using a face-to-face survey.
      Sociodemographic and psychosocial data were collected, as well as information on
      MSP and condomless anal sex. In the 6 months prior to the survey, 54.3% of the
      MSM sample had had MSP. Univariate analysis showed that self-esteem, depression,
      loneliness, sexual compulsivity, and involuntary subordination (IS) were
      associated with MSP. Sexual compulsivity (multivariate odds ratio [ORm] = 2.94,
      95% CI = 1.76-4.91) and IS (ORm = 1.79, 95% CI = 1.14-2.81) remained significant
      in multivariate analysis. MSM with five or more psychosocial problems had greater
      odds of (adjusted odds ratios = 3.06, 95% CI = 1.49-6.25) having MSP in the
      previous 6 months than the non-syndemic group. Our findings provide preliminary
      confirmation of the additive relationship of syndemic psychosocial health
      conditions and MSP among MSM in Shanghai, China. An integrated intervention with
      special focus on sexual compulsivity and IS is needed.

PMID- 29220588
TI  - Latent Growth Curve and Repeated Measures ANOVA Contrasts: What the Models are
      Telling You.
AB  - The relationship between the latent growth curve and repeated measures ANOVA
      models is often misunderstood. Although a number of investigators have looked
      into the similarities and differences among these models, a cursory reading of
      the literature can give the impression that they are very different models. Here
      we show that each model represents a set of contrasts on the occasion means. We
      demonstrate that the fixed effects parameters of the estimated basis vector
      latent growth curve model are merely a transformation of the repeated measures
      ANOVA fixed effects parameters. We further show that differences in fit in models
      that estimate the same means structure can be due to the different error
      covariance structures implied by the model. We show these relationships both
      algebraically and through using data from a simulation.

PMID- 29220581
TI  - High-Stakes Collaborative Testing: Why Not?
AB  - : Phenomenon: Studies of high-stakes collaborative testing remain sparse,
      especially in medical education. We explored high-stakes collaborative testing in
      medical education, looking specifically at the experiences of students in
      established and newly formed teams. APPROACH: Third-year psychiatry students at 5
      medical schools across 6 sites participated, with 4 participating as established
      team sites and 2 as comparison team sites. For the collaborative test, we used
      the National Board of Medical Examiners Psychiatry subject test, administering it
      via a 2-stage process. Students at all sites were randomly selected to
      participate in a focus group, with 8-10 students per site (N = 49). We also
      examined quantitative data for additional triangulation. FINDINGS: Students
      described a range of heightened emotions around the collaborative test yet
      perceived it as valuable regardless if they were in established or newly formed
      teams. Students described learning about the subject matter, themselves, others,
      and interpersonal dynamics during collaborative testing. Triangulation of these
      results via quantitative data supported these themes. Insights: Despite student
      concerns, high-stakes collaborative tests may be both valuable and feasible. The
      data suggest that high-stakes tests (tests of learning or summative evaluation)
      could also become tests for learning or formative evaluation. The paucity of
      research into this methodology in medical education suggests more research is
      needed.

PMID- 29220584
TI  - Detecting Clusters/Communities in Social Networks.
AB  - Cohen's kappa, a similarity measure for categorical data, has since been applied
      to problems in the data mining field such as cluster analysis and network link
      prediction. In this paper, a new application is examined: community detection in
      networks. A new algorithm is proposed that uses Cohen's kappa as a similarity
      measure for each pair of nodes; subsequently, the kappa values are then clustered
      to detect the communities. This paper defines and tests this method on a variety
      of simulated and real networks. The results are compared with those from eight
      other community detection algorithms. Results show this new algorithm is
      consistently among the top performers in classifying data points both on
      simulated and real networks. Additionally, this is one of the broadest
      comparative simulations for comparing community detection algorithms to date.

PMID- 29220590
TI  - Social Desirability Bias in Pornography-Related Self-Reports: The Role of
      Religion.
AB  - In a large online survey of undergraduates, we examined the degree to which
      social desirability concerns might bias pornography-related self-reports and
      whether these biases are stronger among highly religious participants than among
      less-religious ones. Recent state-level analyses have put forward a controversial
      suggestion that religious individuals tend to search for pornography more than
      their less-religious peers, despite self-reports to the contrary. Such results
      could be explained by a social-desirability bias against reporting the
      consumption of pornography, one that applies specifically to religious
      individuals. Though our findings are limited to undergraduates in the U.S.
      Midwest, we found some evidence that the desire to positively self-present (as
      measured by the Marlowe-Crowne social desirability scale) may bias reports of
      pornography consumption and perceptions of pornography's effects (e.g.,
      perceptions of addictiveness). However, contrary to popular sentiment-and our own
      hypotheses-we found no evidence for and much evidence against the suggestion that
      religious individuals have a more pronounced social desirability bias against the
      reporting of pornography consumption than the irreligious. Interaction terms
      assessing that possibility were either nonsignificant or significant in the
      reverse direction.

PMID- 29220589
TI  - First-Year Internal Medicine Residents' Reflections on Nonmedical Home Visits to
      High-Risk Patients.
AB  - PROBLEM: Patients who are high utilizers of care often experience health-related
      challenges that are not readily visible in an office setting but paramount for
      residents to learn. A nonmedical home visit performed at the beginning of
      residency training may help residents better understand social underpinnings
      related to their patient's health and place subsequent care within the context of
      the patient's life. INTERVENTION: First-year internal medicine residents
      completed a nonmedical home visit to an at-risk patient prior to seeing the
      patient in the office for his or her first medical visit. CONTEXT: We performed a
      thematic analysis of internal medicine interns' (n = 16) written narratives on
      their experience of getting to know a complex patient in his or her home prior to
      seeing the patient for a medical visit. Narratives were written by the residents
      immediately following the visit and then again at the end of the intern year, to
      assess for lasting impact of the intervention. Residents were from an urban
      academic residency program in Baltimore, Maryland, USA. OUTCOME: We identified
      four themes from the submitted narratives. Residents discussed the visit's impact
      on future practice, the effect of the community and support system on health, the
      impact on the depth of the relationship, and the visit as a source of
      professional fulfillment. Whereas the four themes were present at both time
      points, the narratives completed immediately following the visit focused more on
      the themes of impact of future practice and the effect of the community and
      support system on health. The influence of the home visit on the depth of the
      relationship was a more prevalent theme in the end-of-the-year narratives.
      LESSONS LEARNED: Although there is evidence to support the utility of learners
      completing medical home visits, this exploratory study shows that a nonmedical
      home visit can be rewarding and formative for early resident physicians. Future
      studies could examine the patient's perspective on the experience and whether a
      nonmedical home visit is a valuable tool in other patient populations.

PMID- 29220580
TI  - The influence of adiposity and acute exercise on circulating hepatokines in
      normal-weight and overweight/obese men.
AB  - Hepatokines are liver-secreted proteins with potential to influence glucose
      regulation and other metabolic parameters. This study investigated differences in
      adiposity status on 5 novel hepatokines and characterised their response to acute
      moderate-intensity exercise in groups of normal-weight and overweight/obese men.
      Twenty-two men were recruited into normal-weight and overweight/obese groups
      (body mass index: 18.5 to 24.9 and 25.0 to 34.9 kg.m-2). Each completed 2
      experimental trials, exercise and control. During exercise trials, participants
      performed 60 min of moderate-intensity treadmill exercise (~60% peak oxygen
      uptake) and then rested for 6 h. Participants rested throughout control trials.
      Circulating fibroblast growth factor-21 (FGF21), follistatin, leukocyte cell
      derived chemotaxin 2 (LECT2), fetuin-A, and selenoprotein-P (SeP) were measured
      throughout. Fasted (resting) FGF21 and LECT2 were higher in overweight/obese
      individuals (129% and 55%; P <= 0.01) and correlated with indices of adiposity
      and insulin resistance; whereas circulating follistatin was lower in
      overweight/obese individuals throughout trial days (17%, P < 0.05). In both
      groups, circulating concentrations of FGF21 and follistatin were transiently
      elevated after exercise for up to 6 h (P <= 0.02). Circulating fetuin-A and SeP
      were no different between groups (P >= 0.19) and, along with LECT2, were
      unaffected by exercise (P >= 0.06). These findings show that increased adiposity
      is associated with a modified hepatokine profile, which may represent a novel
      mechanism linking excess adiposity to metabolic health. Furthermore, acute
      perturbations in circulating FGF21 and follistatin after exercise may contribute
      to the health benefits of an active lifestyle.

PMID- 29220585
TI  - "It Takes a Man to Put Me on the Bottom": Gay Men's Experiences of Masculinity
      and Anal Intercourse.
AB  - In anal intercourse between gay men, men who are typically insertive ("tops") are
      often perceived as, and may identify as, more masculine than those who are
      typically receptive ("bottoms"). "Versatile" men, who may adopt either position,
      may be perceived as more gender balanced and may transcend the gender-role
      stereotypes associated with self-labeling as top or bottom. The aim of this study
      was to explore how gay men's beliefs about masculinity were associated with their
      beliefs about the gendered nature of sexual self-labels and their behavior in
      anal intercourse. Individual semistructured interviews were undertaken with 17 UK
      based gay men. Interpretative phenomenological analysis (IPA) identified that
      perceptions of tops and bottoms as gendered social identities varied depending on
      the extent to which gay men subscribed to the mandates of hegemonic masculinity,
      the dominant masculinity in Western society. The findings also suggested that
      some gay men differentiated between top and bottom as social identities and
      topping and bottoming as gendered behaviors. This had implications for gay men's
      behaviors in anal intercourse. It is suggested that future efforts to engage with
      gay men about their sexual behavior should account for their beliefs regarding
      the gender-role stereotypes associated with gay sexual self-labels.

PMID- 29220594
TI  - Modification of immunological features in human platelets during sepsis.
AB  - Sepsis is an organic dysfunction that puts at risk the life of patients suffering
      this disorder due to an exacerbated immunological response to the infection
      mediated by the host. Platelets have been largely researched on sepsis owing to
      its role in Disseminated Intracellular Coagulation (DIC) and because
      thrombocytopenia is an important clinical feature of these patients.
      Nevertheless, a great number of evidence shows that platelets have also an
      important role in immunological response since they have pattern recognition
      receptors, chemokine receptors and granules with stored soluble mediators. In
      this work, the immunological features of platelets in individuals with sepsis are
      described. The results show that platelets of these individuals have high levels
      of surfaces expression of TLR4, CD62P, CD32 and thrombin receptor 1 (PAR-1),
      these platelets have also greater capability to join Escherichia coli, and show a
      different profile of soluble mediators (IL-1beta, CD40L and TNF-alpha). Platelets
      from patients with sepsis form aggregates with neutrophils in circulation, but
      are unable to induce the production of reactive oxygen species. This research
      describes important features of platelets to help the understanding of the
      immunological role of these cells in sepsis.

PMID- 29220593
TI  - Accounting for Missing Correlation Coefficients in Fixed-Effects MASEM.
AB  - Meta-analytic structural equation modeling (MASEM) is increasingly applied to
      advance theories by synthesizing existing findings. MASEM essentially consists of
      two stages. In Stage 1, a pooled correlation matrix is estimated based on the
      reported correlation coefficients in the individual studies. In Stage 2, a
      structural model (such as a path model) is fitted to explain the pooled
      correlations. Frequently, the individual studies do not provide all the
      correlation coefficients between the research variables. In this study, we modify
      the currently optimal MASEM-method to deal with missing correlation coefficients,
      and compare its performance with existing methods. This study is the first to
      evaluate the performance of fixed-effects MASEM methods under different levels of
      missing correlation coefficients. We found that the often used univariate methods
      performed very poorly, while the multivariate methods performed well overall.

PMID- 29220592
TI  - Different loci and mRNA copy number of the increased serum survival gene of
      Escherichia coli.
AB  - The increased serum survival gene (iss) has been identified as a virulence trait
      associated with the virulence of Escherichia coli, causing colibacillosis in
      poultry. However, it remains unclear as to whether iss mRNA copy number and
      sequence affect virulence. To examine these influences, we assessed the presence
      of iss, sequence analysis, iss mRNA copy number, and serum resistance. The iss
      gene was detected in 88 (all) E. coli isolates from different sources, and
      sequencing identified 16 alleles (32 different loci) and 10 amino acid sequences
      (10 different loci). Nested polymerase chain reaction improved iss detection. The
      isolates from sick chickens had >68% livability in serum resistance tests and
      higher iss mRNA copy number. The iss mRNA copy number highly correlated with
      mortality and E. coli livability. Student's t tests confirmed the relationship
      between the different loci to iss transcription, serum resistance, and virulence.
      These data suggest that iss mRNA copy number and different loci affect the
      virulence and serum resistance. These findings could be useful in further studies
      on the prevalence of iss among E. coli isolates and other virulence factors.

PMID- 29220591
TI  - Cholinergic and cytoprotective signaling cascades mediate the mitigative effect
      of erythropoietin on acute radiation syndrome.
AB  - The present investigation aimed to evaluate the radiomitigative efficacy of the
      recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in
      a rat model. Rats were irradiated with a single sublethal dose of gamma-radiation
      (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then
      received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed
      for 30 days of survival analysis. Administration of EPO improved 30-day survival,
      alleviated TBI-induced myelosuppression and pancytopenia, by augmenting
      lymphocytes and other white blood cells in the peripheral blood of rats, while
      bone marrow and spleen cellularity were restored. EPO post-exposure treatment
      alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated
      radiation-induced oxidative stress through the upregulation of the cholinergic
      anti-inflammatory nicotinic acetylcholine receptor (alpha-7-nAChR) and the pro
      survival Janus kinase-2 and signal transducers and activators of transcription
      JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related
      factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats.
      Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present
      study establishes the implication of alpha-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling
      cascade in the radiomitigative potential of EPO against ARS.

PMID- 29220598
TI  - Hope for the Future But Fear the Risk of Stigma: Ethiopian Family Caregivers'
      Lived Experience of Caring for Their HIV Positive Child Two Years After Starting
      Antiretroviral Treatment.
AB  - Family caregivers are believed to be the primary source of support for HIV
      affected children. There is limited evidence about practices of support for
      caregivers, to strengthen them and to enhance the welfare of HIV positive
      children, especially in African settings. Our aim was therefore to illuminate
      caregivers' lived experiences of caring for a child in Ethiopia 2 years after the
      child was enrolled in antiretroviral therapy. Qualitative interviews with 18
      family caregivers of 18 children were performed and analyzed using an inductive
      design with a hermeneutic phenomenological approach. The family caregivers' lived
      experience was shown in two main themes comprising "lifelong medication gives
      hope for the future" and "support challenged by the fear of stigma." The family
      caregivers experienced hope and dreams for the future as they saw their child as
      healthy and they had regained normality in life after the child's diagnosis. The
      caregivers still feared the disclosure of the child's diagnosis, which gave rise
      to conflicts with the child, the family, and society. Good quality support from
      the healthcare staff lightened their burdens. Further studies are recommended on
      the strategies of stigma reduction and developing need-specific modalities to
      support caregivers in the community.

PMID- 29220595
TI  - Dose dependent effects of tadalafil and roflumilast on ovalbumin-induced airway
      hyperresponsiveness in guinea pigs.
AB  - INTRODUCTION: Chronic obstructive diseases of airways associated with cough
      and/or airway smooth muscle hyperresponsiveness are usually treated with
      bronchodilating and anti-inflammatory drugs. Recently, selective
      phosphodiesterase (PDE) 4 inhibitors have been introduced into the therapy of
      chronic obstructive pulmonary disease. Several studies have demonstrated their
      ability to influence the airway reactivity and eosinophilic inflammation by
      increasing the intracellular cAMP concentrations also in bronchial asthma.
      Furthermore, the expression of PDE5 in several immune cells suggests perspectives
      of PDE5 inhibitors in the therapy of inflammation, as well. PURPOSE: The aim of
      this study was to assess the dose-dependent effects of PDE4 and PDE5 inhibitors
      in allergic inflammation. Therefore, the effects of 7-days administration of PDE4
      inhibitor roflumilast and PDE5 inhibitor tadalafil at two different doses in
      experimentally-induced allergic inflammation were evaluated. MATERIALS AND
      METHODS: In the study, male adult guinea pigs were used. Control group was non
      sensitized. Other animals were sensitized with ovalbumin over two weeks and
      thereafter treated intraperitoneally for 7 days with roflumilast or tadalafil
      (daily dose 0.5 mg/kg or 1.0 mg/kg b.w.), or with vehicle. RESULTS: Both
      roflumilast and tadalafil reduced specific airway resistance after nebulization
      of histamine (marker of in vivo airway reactivity) at both doses used. The in
      vitro airway reactivity to cumulative doses of acetylcholine was significantly
      reduced for roflumilast at higher dose, predominantly in the lung tissue strips.
      Histamine-induced contractile responses were significantly influenced in both
      lung and tracheal tissue strips, predominantly at the higher doses. Tadalafil led
      to a decrease in contractile responses induced by both acetylcholine and
      histamine, with more significant effects in the lung tissue strips. These changes
      were associated with decreased numbers of circulating leukocytes and eosinophils
      and concentrations of interleukin (IL)-4, IL-5 and TNF-alpha in the lung
      homogenate. CONCLUSIONS: The selective PDE4 and PDE5 inhibitors alleviated
      allergic airway inflammation, with more significant effects at the higher doses.

PMID- 29220602
TI  - An Observational Study of Treatment Seeking Users of Natural Opiates from India.
AB  - BACKGROUND: The type of opioid used influences the severity and complications
      experienced. Natural opiates (opium and poppy husk) use is a socio-culturally
      accepted phenomenon reported in India. However, studies on their profile, quality
      of life, and addiction severity are limited. OBJECTIVES: The objective of this
      cross-sectional, observational study was to assess the socio-demographic profile,
      clinical profile, addiction severity, and quality of life of treatment-seeking
      natural opiate users. METHOD: Hundred subjects aged 18-65 years using opium or
      poppy husk seeking outpatient treatment at a tertiary addiction treatment center
      in India were interviewed to collect information on their socio-demography,
      natural opiate, and other substance use. Additionally, their addiction severity
      and quality of life were assessed using Addiction Severity Index-Lite and WHO
      Quality of Life-Bref instrument, respectively. RESULTS: All subjects were male
      with a mean age of 44.6 (+/-11.0) years. Majority (97%) used poppy husk daily
      orally. Curiosity/experimentation (63%) was the most common reason for starting
      opiate use. The past month rates of tobacco, alcohol, cannabis, and sedative
      hypnotics use was 58%, 33%, 3%, and 12%, respectively. Only 4% injected any
      opioid. Inability to afford opiates (72%) was the most common reason for seeking
      treatment. Rates of medical, familial, social, psychological, and legal
      complications were low, while the WHOQOL-BREF scores fell between 40 and 50
      across various domains. Conclusions/Importance: Natural opiate users may
      constitute distinct subgroup of opioid users with fewer/no complications despite
      long duration of uninterrupted use. These findings would be important in planning
      management strategies for people dependent on natural opiates.

PMID- 29220603
TI  - Evaluating Dispatch-Assisted CPR Using the CARES Registry.
AB  - OBJECTIVES: Dispatch-assisted cardiopulmonary resuscitation (DA-CPR) has been
      shown to improve cardiac arrest survival. Recent literature has proposed dispatch
      metrics for provision of this intervention. Our objectives are to: use the
      Cardiac Arrest Registry to Enhance Survival (CARES) to compare current practice
      to proposed DA-CPR guidelines; describe barriers to DA-CPR; and assess the
      association of DA-CPR with out-of-hospital cardiac arrest (OHCA) survival.
      METHODS: We reviewed data from structured dispatch reviews of 911 OHCA calls from
      1/1/14-12/31/15. Dispatch data including whether dispatch CPR instruction was
      given, and time intervals to CPR instruction and provision were linked with OHCA
      data elements from field cardiac arrest process and outcome data. Descriptive
      data on barriers to dispatch-caller instruction and measures of dispatcher
      performance were calculated. We compared outcome of patients who received
      bystander CPR prior to the 911 call (BCPR), after dispatcher CPR instructions (DA
      CPR), and not until Emergency Medical Services (EMS) arrival (no BCPR). RESULTS:
      We identified 3335 cases from 32 dispatch agencies in 9 states that had dispatch
      and outcome data. CPR was performed prior to the 911 call by a bystander in 496
      (14.9%) cases. Of all calls where the dispatcher talked to a bystander,
      dispatchers recognized cardiac arrest in 82.9% cases (1514/1827), with 31.6%
      calls recognized in <60 seconds. DA-CPR instructions were initiated in most
      (1320/1514, 87.2%) cases, and cardiac compressions were initiated in 73.7%
      (973/1320). DA-CPR was performed < two minutes in 21.4% of cases. In a
      multivariable analysis, BCPR (CPR prior to EMS arrival without instructions
      given) was associated with significantly improved patient survival (OR = 1.49,
      95% CI 1.09, 2.04), and DA-CPR a non-significant improvement in survival to
      discharge (OR = 1.19, 95% CI 0.91, 1.56). CONCLUSIONS: Temporal measures of
      dispatch performance were substantially below proposed national standards. In
      this population, OHCA was frequently recognized and DA-CPR performed but was not
      associated with a significant improvement in survival.

PMID- 29220605
TI  - NUT Midline Carcinoma of the Lung in a Six-Year-Old Child.
AB  - BACKGROUND: Nuclear protein of the testis (NUT) midline carcinoma is genetically
      defined by rearrangement of NUT or by immunohistochemical expression of NUT.
      FINDINGS: A 6-year old child had a NUT midline carcinoma of the lung. Despite
      aggressive therapy, the child died. CONCLUSION: NUT carcinoma, which can be
      diagnosed immunohistochemically, remains an aggressive tumor.

PMID- 29220609
TI  - Evaluation of Structured Assessment and Mediating Factors of Suicide-Focused
      Group Therapy for Veterans Recently Discharged from Inpatient Psychiatry.
AB  - The current study investigated the impact of adding the Suicide Status Form (SSF)
      to a suicide-focused group therapy for veterans recently discharged from an
      inpatient psychiatry setting. A sample of 141 veterans was enrolled and
      randomized into a Usual Assessment Group Therapy or SSF-Assessment Group Therapy.
      Participants completed interviews at baseline, 1, and 3 months. No significant
      differences were observed between groups regarding group attendance (IRR = 1.01,
      Std. Err = 0.08, 95% CI = 0.87, 1.18) or client satisfaction (beta = 0.23, Std.
      Err = 0.66, p = 0.73, d = -.25). No main effects were observed across the study
      on secondary outcomes of interest for suicidal ideation and overall symptom
      distress, although participants in both treatment conditions reported significant
      improvements on these outcomes over the course of the study. Patients in the
      Usual Assessment Group Therapy demonstrated greater reductions in overall symptom
      distress across the 3-month follow-up window (beta = 6.08, Std. Err = 2.04, p =
      0.003; f2 = 0.05). Follow-up path analyses revealed that more frequent session
      attendance was significantly related to less suicidal ideation at 1-month, higher
      working alliance between individual members and group facilitators was associated
      with greater suicidal ideation at 1-month, and higher group cohesion among group
      members at 1-month was significantly associated with less thwarted belongingness
      at 1-month. Although the SSF did not improve the impact of an existing suicide
      focused group therapy, the study findings support future research on group
      treatments for suicidal veterans.

PMID- 29220611
TI  - Violent Lives: Pathways Linking Exposure to Violence To Suicidal Behavior in a
      National Sample.
AB  - This study explored the extent to which depression, somatic symptoms, and
      substance use mediated the effects of exposure to violence on suicidal ideation
      and attempted suicide, and whether these pathways varied across gender, age, and
      race/ethnicity. Path analysis was conducted on 12,272 adolescents (mean = 15.3
      years) from the National Longitudinal Study of Adolescent to Adult Health. The
      impact of exposure to violence on suicidal ideation was fully mediated, and the
      impact of exposure to violence on attempted suicide was partially mediated by
      depression, somatic symptoms, and substance use. Mediating pathways were stronger
      for females and for younger adolescents. Understanding the impact of exposure to
      violence on adolescent suicidal behavior requires the consideration of direct,
      indirect, and conditional indirect effects.

PMID- 29220608
TI  - Factors that Differentiate Prescription Stimulant Misusers from those At-Risk for
      Misuse: Expectancies, Perceived Safety, and Diversion.
AB  - BACKGROUND: The nonmedical use of prescription stimulants (NMUPS) is one of the
      most prevalent illicit behaviors on college campuses. While numerous risk factors
      for NMUPS have been identified, it is unknown how nonusing students who meet
      several risk factors for NMUPS differ from those who have used, which may inform
      intervention efforts. We expected that users would evidence greater cognitive
      enhancement and anxiety/arousal expectancies and intentions to use, and lower
      guilt/dependence expectancies, perceptions of NMUPS-related harm, and academic
      self-efficacy. METHODS: Between 2014 and 2016, students (N = 121; 65% female) at
      two demographically dissimilar colleges in the Northeastern and Midwestern United
      States who reported lifetime NMUPS or endorsed two or more NMUPS risk factors
      (i.e., recent marijuana use, recent binge drinking, grade point average <3.5,
      Greek-life involvement, male gender) reported on their prescription stimulant
      expectancies; academic self-efficacy; perceived harm of NMUPS; lifetime NMUPS;
      and intentions for NMUPS in the next six months. RESULTS: A MANCOVA showed that
      at-risk nonusers had lower cognitive expectancies, higher guilt/dependence
      expectancies, and higher anxiety/arousal expectancies compared to users. ANCOVAs
      and Chi-square tests showed that nonusers also perceived NMUPS to be more harmful
      and were less likely to divert their medication if prescribed. The groups did not
      differ on academic self-efficacy or total number of risk factors endorsed.
      However, recent marijuana use was more prevalent in users. CONCLUSIONS: Targeted
      preventive interventions for NMUPS should focus on students who are using
      marijuana and should aim to maintain lower positive and higher negative stimulant
      expectancies and reaffirm potential NMUPS-related harms.

PMID- 29220607
TI  - Case of cone dystrophy with normal fundus appearance associated with biallelic
      POC1B variants.
AB  - BACKGROUND: Biallelic variants of POC1B were recently reported to cause autosomal
      recessive non-syndromic cone dystrophy. However, the number of studies supporting
      this is limited, and the clinical phenotypes of cone dystrophy have not been
      definitively determined. The purpose of this study was to report the phenotype of
      a case of POC1B-associated cone dystrophy. MATERIALS AND METHODS: The medical
      chart of one case diagnosed with cone dystrophy was reviewed. RESULTS: The
      patient was a 20-year-old Japanese man whose chief complaint was a progressive
      decrease in his central vision. His decimal best-corrected visual acuity was 0.2
      for the right and 0.3 for the left. Fundus examinations showed no abnormalities.
      The photopic electroretinograms were nonrecordable, but the scotopic
      electroretinograms were within normal limits. Optical coherence tomography
      detected a blurry line in the region of the external limiting membrane and
      ellipsoid zone. Adaptive optics images showed sparsely distributed cone cells
      around the fovea. The patient was initially diagnosed with incomplete
      achromatopsia. Whole-exome sequence with targeted analysis identified new
      compound heterozygous mutations of c.G1355A (p R452Q) and c.C987A (pY329X) in the
      POC1B gene. The patient was then diagnosed with cone dystrophy. CONCLUSIONS: The
      cone dystrophy associated with POC1B variants has features similar to
      achromatopsia, and genetic analyses is useful in discriminating these two
      diseases.

PMID- 29220597
TI  - Dietary NaCl affects bleomycin-induced lung fibrosis in mice.
AB  - PURPOSE: High levels of NaCl in the diet are associated with both cardiac and
      renal fibrosis, but whether salt intake affects pulmonary fibrosis has not been
      examined. AIM OF THE STUDY: To test the hypothesis that salt intake might affect
      pulmonary fibrosis. MATERIALS AND METHODS: Mice were fed low, normal, or high
      salt diets for 2 weeks, and then treated with oropharyngeal bleomycin to induce
      pulmonary fibrosis, or oropharyngeal saline as a control. RESULTS: As determined
      by collagen staining of lung sections, and protein levels and cell numbers in the
      bronchoalveolar lavage (BAL) fluid at 21 days after bleomycin, the high salt diet
      did not exacerbate bleomycin-induced fibrosis, while the low salt diet attenuated
      fibrosis. For the bleomycin-treated mice, staining of the post-BAL lung sections
      indicated that compared to the regular salt diet, high salt increased the number
      of Ly6c-positive macrophages and decreased the number of CD11c and CD206-positive
      macrophages and dendritic cells. The low salt diet caused bleomycin-induced
      leukocyte numbers to be similar to control saline-treated mice, but reduced
      numbers of CD45/collagen-VI positive fibrocytes. In the saline controls, low
      dietary salt decreased CD11b and CD11c positive cells in lung sections, and high
      dietary salt increased fibrocytes. CONCLUSIONS: Together, these data suggest the
      possibility that a low salt diet might attenuate pulmonary fibrosis.

PMID- 29220610
TI  - Predictors of Alcohol Use during Pregnancy among Women Attending Midwife
      Obstetric Units in the Cape Metropole, South Africa.
AB  - INTRODUCTION: Little is known about the nature and extent of substance use among
      pregnant women in Cape Town (South Africa) despite the very high levels of
      substance use and related consequences such as FASD in this part of the country.
      The aim of the study was to determine predictors of alcohol use among pregnant
      women. METHODS: A cross-sectional survey was conducted among pregnant women
      attending 11 Midwife Obstetric Units (MOUs) in greater Cape Town. A two-stage
      cluster survey design was used. In total, 5231 pregnant women were screened to
      assess self-reported prevalence estimates. Of these, 684 (13.1%) were
      intentionally sub-sampled and completed an interviewer-administered questionnaire
      and provided a urine sample for biological screening. Univariate and multivariate
      statistical procedures were used to determine factors predictive of alcohol use.
      RESULTS: Findings highlight various demographic, social and partner substance use
      predictors for both self-reported and biologically verified alcohol use in two
      different models. Being Coloured, having a marital status other than being
      married, experiencing violence or aggression in the past 12 months compared to
      more than 12 months ago, having a partner who drinks, and partner drug use are
      all independently associated with higher odds of self-reported alcohol use. In
      contrast, only partner tobacco use is independently associated with higher odds
      of biologically verified alcohol use. CONCLUSION: Knowing the risk factors for
      alcohol use in pregnancy is important so that intervention efforts can accurately
      target those women in need of services. Intervention programs addressing risk
      factors of high-risk pregnant women are needed.

PMID- 29220612
TI  - Coexistence of Trisomy 13 and SRY (-) XX Ovotesticular Disorder of Sex
      Development.
AB  - INTRODUCTION: Ovotesticular disorder of sex development (OT-DSD) is a rare
      disorder of sexual differentiation characterized by the presence of both
      testicular and ovarian tissue in an individual and the majority of cases have
      been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation
      may occur due to the translocation of SRY to the X chromosome or to an autosome.
      CASE REPORT: Herein, we present a female newborn with a combination of trisomy 13
      and SRY (-) XX OT-DSD. CONCLUSION: Trisomy 13 is a relatively common and well
      known chromosomal disorder in which disorders of sexual differentiation are not
      frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased
      expression of pro-ovarian/anti-testis genes have been suggested as underlying
      mechanisms of testicular formation. The findings in this patient were suggestive
      of an underlying genomic disorder associated with FGF9 and/or SPRY2.

PMID- 29220614
TI  - Religious Coping and Suicide Risk in a Sample of Recently Returned Veterans.
AB  - The aim of the present study is to examine religious coping and depression as
      predictors of suicide risk in a large U.S. veteran sample from recent conflicts.
      Demographic, military history, depressive symptomatology, positive and negative
      religious coping and self-reported suicidal behavior were analyzed in a sample of
      772 recently returned veterans. Suicide risk was computed as a continuum of risk
      across 4 separate categories. Negative religious coping was significantly
      associated with suicide risk, even after statistically controlling for depressive
      symptomatology and other variables. The present analysis did not find any
      significant relationships for positive religious coping. No significant gender
      interaction effects were found. The present findings support the importance of
      understanding veteran experiences of religious coping, particularly negative
      religious coping, in the context of suicide prevention efforts.

PMID- 29220613
TI  - Fully Automated Pipetting Sorting System for Different Morphological Phenotypes
      of Zebrafish Embryos.
AB  - Systems biology methods, such as transcriptomics and metabolomics, require large
      numbers of small model organisms, such as zebrafish embryos. Manual separation of
      mutant embryos from wild-type embryos is a tedious and time-consuming task that
      is prone to errors, especially if there are variable phenotypes of a mutant. Here
      we describe a zebrafish embryo sorting system with two cameras and image
      processing based on template-matching algorithms. In order to evaluate the
      system, zebrafish rx3 mutants that lack eyes due to a patterning defect in brain
      development were separated from their wild-type siblings. These mutants show
      glucocorticoid deficiency due to pituitary defects and serve as a model for human
      secondary adrenal insufficiencies. We show that the variable phenotypes of the
      mutant embryos can be safely distinguished from phenotypic wild-type zebrafish
      embryos and sorted from one petri dish into another petri dish or into a 96-well
      microtiter plate. On average, classification of a zebrafish embryo takes
      approximately 1 s, with a sensitivity and specificity of 87% to 95%,
      respectively. Other morphological phenotypes may be classified and sorted using
      similar techniques.

PMID- 29220616
TI  - Interventions to Improve or Maintain Lower-Limb Function Among Ambulatory
      Adolescents with Cerebral Palsy: A Cross-Sectional Survey of Current Practice in
      the UK.
AB  - OBJECTIVES: To describe physiotherapy management to improve or maintain lower
      limb function among adolescents with cerebral palsy, classified in Gross Motor
      Function Classification System levels I-III, in the United Kingdom (UK). METHODS:
      A list of interventions was identified using a nominal group technique and
      developed into a survey, which was distributed to approximately 2,100 pediatric
      physiotherapists in the UK through the Association of Pediatric Chartered
      Physiotherapists and a private physiotherapy clinic in London between April and
      June 2015. One-hundred and thirty-five physiotherapists completed the survey.
      Survey respondents indicated how frequently they used each intervention (i.e.,
      "frequently," "sometimes," "rarely," and "never") in the past year. RESULTS:
      Provision of explanations to the child, liaison with families, liaison with
      health professionals, provision of advice to schools, and stretching were the
      most frequently used interventions with 90%, 90%, 86%, 79%, and 76% of
      respondents, respectively, reporting that they frequently used each. The
      interventions most commonly reported as "never" used were conductive education
      (88%), MOVE programme (85%), functional electrical stimulation (82%), body-weight
      supported treadmill training (80%), and rebound therapy (71%). CONCLUSIONS: This
      study suggests that a large number of interventions are used by physiotherapists
      in the United Kingdom to improve or maintain lower-limb function among
      adolescents with CP, not all of which are evidence-based.

PMID- 29220622
TI  - Regimen Difficulty and Medication Non-Adherence and the Interaction Effects of
      Gender and Age.
AB  - Medication non-adherence is a global health issue. Numerous factors predict it.
      This study is aimed to identify the association between regimen difficulty and
      medication non-adherence among patients with chronic conditions and testing the
      interaction effects of gender and age on the same. It was a cross-sectional study
      conducted among 479 outpatients from India. Convenience sampling method was used.
      Multiple regression analyses were performed to find the predictors of non
      adherence and to test interaction effects. Regimen difficulty predicted
      medication non-adherence. The patient's gender and age have interaction effects
      on the relationship between regimen difficulty and medication non-adherence.

PMID- 29220618
TI  - Psychological Comfort of Paramedics with Field Death Pronouncement: A National
      Asian Study to Prepare Paramedics for Field Termination of Resuscitation.
AB  - OBJECTIVES: Paramedics' decision to terminate field resuscitation without a
      physician present may depend on personal and external factors. This study
      investigates factors associated with paramedic psychological comfort with
      termination of resuscitation (TOR) to inform future training. METHODS: We
      administered an anonymous survey to all practicing paramedics in a large urban
      Asian Emergency Medical Services system where formal TOR training had not yet
      been conducted and field TOR was not routinely applied. The survey assessed
      psychological comfort using the validated Psychological Comfort Total (PCT) scale
      (summed score of 28 items, with higher scores representing greater comfort). We
      examined scores associated with four personal (prior resolution of personal loss,
      knowledge of survival probability, religious affiliation and experience with
      death pronouncements) and two external (location of patient and perceived trust
      of family) factors. Data were entered into Excel and analyzed by t-tests and
      ANOVA. RESULTS: Response rate was 73.6% (254/345). Respondents were 30.3 years
      (mean, SD 7.1) with 7.2 years (mean, SD 5.54) of practice experience. Over 60%
      had been involved in 6 or more field death pronouncements in the prior 12 months.
      Higher PCT scores were associated with prior resolution of personal loss and
      knowledge of survival probability. Lower PCT scores were associated with patient
      location in a public place and perceived family lack of trust. PCT scores were
      not associated with paramedic religious affiliation or number of prior death
      pronouncements. CONCLUSIONS: Paramedic psychological comfort with field death
      pronouncement is associated with personal and external factors. Since paramedic
      comfort is important for protocol adoption, TOR education should target not only
      knowledge, but also public arena management, communication skills for engaging
      with families, and help paramedics resolve prior personal loss.

PMID- 29220626
TI  - Introductory to Issue 41(1): Navigating Thorny Aspects of Dementia Care: Sex,
      Money, Cars and More.

PMID- 29220621
TI  - Quality of Life in Australian Adults Aged 50 Years and Over: Data Using the
      Schedule for the Evaluation of Individual Quality of Life (SEIQOL-DW).
AB  - OBJECTIVES: This study explored unique and personal domains associated with
      quality of life (QOL) in 153 mid-aged and older Australian adults over age 50,
      using an innovative measure of individualized QOL, the Schedule for the
      Evaluation of Individual Quality of Life (SEIQOL-DW). METHODS: Demographic
      measures as well as the SEIQOL-DW were administered. The qualitative responses on
      this scale were analyzed by Leximancer, a text analysis program that extracts
      semantic meaning and relational information automatically from text. RESULTS: For
      the sample as a whole, the most important QOL domain was found to be
      Relationships, followed by Family, Health, Activities, Community, Security,
      Beliefs, Independence and finally Wellbeing. When the sample was broken down into
      age bands for analysis, the most important domain theme was Family (50-59 year
      olds), Relationships (60-69 year olds), Relationships (70-79 year olds), and
      Health (80+ year olds). CONCLUSIONS: The wide range of concepts elicited in each
      domain via Leximancer underscores the argument for analyzing QOL in an
      individualized way, as it was clear from these concepts that different domains
      had unique meanings to each person. CLINICAL IMPLICATIONS: Understanding QOL at
      the level of which domains in an individual are important to QOL in later life is
      critical to providing services to both healthy aged as well as those with health
      and mental health needs. The SEIQOL-DW affords clinicians a unique tool with
      which to describe an individual's unique and relevant quality of life areas, and
      affords a way to measure change in these areas as a result of interventions.

PMID- 29220615
TI  - Medication-Assisted Treatment (MAT) for Opioid Addiction: Introduction to the
      Special Issue.
AB  - Several countries are experiencing public health crises as a result of opioid
      addiction. Fatal overdoses have reached record highs in many regions and
      Hepatitis C virus is the norm among people who inject drugs in several countries.
      Thus, providing for the global availability of medication-assisted treatment
      (MAT) for opioid addiction is more important than ever. In this article, we
      introduce readers to the collection of papers that appear in this special issue
      on MAT for opioid addiction. We describe the articles and commentaries
      thematically to include topics that address 1) the contemporary history of
      methadone maintenance, 2) the provision of and access and barriers to MAT, 3)
      compliance and outcomes of MAT, 4) health issues among MAT patients, 5) race,
      ethnicity, and social class backgrounds of MAT patients, 6) criminalization and
      stigma, and 7) challenges associated with the expansion of MAT.

PMID- 29220624
TI  - Godly Homonormativity: Christian LGBT Organizing in Contemporary Poland.
AB  - This article discusses the emergence of Christian LGBT organizing in Poland and
      the production of what I term godly homonormativity via a particular strand of
      organizing exemplified by Wiara i Tecza (WiT; Faith and Rainbow). I argue that
      despite being an important initiative representing people-LGBT Christians-whose
      voices are often excluded from the mainstream LGBT movement, WiT's project is a
      largely assimilationist one, seeking acceptance within the existing patriarchal
      and highly inequitable power relationship of the Catholic Church. Consequently,
      WiT is generative of a mostly normalizing set of ideas that reinforces rather
      than challenges heteronormativity and that also colludes with the neoliberal
      project that promotes "a privileged form of gay life that attempts to replicate
      aspects of state"-and in the case of WiT church-endorsed "heterosexual primacy
      and prestige located in the home" (Brown, 2009, p. 1499).

PMID- 29220625
TI  - Feasibility of Training and Delivering Compassionate Touch in Long-Term Care.
AB  - OBJECTIVES: Limited evidence supports the use of therapeutic touch for people
      with dementia (PWD). Interventions incorporating a person-centered approach to
      touch delivered by staff may benefit PWD and staff in long-term care settings.
      The Compassionate Touch(r) (CT) program provides skilled human touch and a
      compassionate presence following a person-centered approach and touch protocol.
      The purpose of this study was to determine the feasibility of training and
      delivering CT. METHODS: An online survey was sent via email to 112 staff who
      attended the CT coach training. Descriptive statistics and thematic analysis were
      used to analyze closed-and open-ended questions of the survey. RESULTS: Twenty
      four staff members completed the survey and reported positive perspectives about
      the training, use of the program, and benefits for PWD and themselves. Five
      themes emerged, including (1) benefits for residents, (2) challenges in using CT,
      (3) when to use CT, (4) training staff, and (5) needed support. CONCLUSIONS:
      Preliminary findings from the present research show potential benefits of using
      the CT program for residents, challenges participants faced in using the program
      and training other staff, and support needed to overcome these challenges.
      CLINICAL IMPLICATIONS: Programs such as CT may benefit PWD and staff in
      residential care settings.

PMID- 29220619
TI  - The Effect of Whole-Body Vibration on Lower-Body Resistance Detraining in College
      Age Women.
AB  - PURPOSE: This study explored the effect of whole-body vibration (WBV) using
      accelerations of 2.56 g to 7.68 g on lower-body detraining. METHODS: All
      participants (N = 20) were trained using a lower-body resistance-training program
      for 30 min twice per week from Week 0 to Week 6. At the end of the program, they
      were randomly assigned to a control group that performed no further training or a
      WBV group that performed a progressive static WBV program. Data for the 5
      repetition-maximum (5RM) squat and extensors and flexors of the knee and ankle
      were collected at Weeks 0, 6, 8, 10, and 12 for all participants. RESULTS: Two
      way (condition vs. time) analysis of variance revealed that although the WBV
      group maintained strength in the 5RM from Week 6 through Week 8 and the control
      group had a lower 5RM in Week 8 from Week 6, no differences in the 5RM squat
      existed between the groups at Week 8. Two-way factorial multivariate analysis of
      variance revealed no differences between the groups at any of the time for torque
      of knee flexion, dorsiflexion, or plantar flexion. CONCLUSION: Static WBV of 2.56
      g to 7.68 g did not attenuate detraining of the flexors and extensors of the knee
      and ankle.

PMID- 29220617
TI  - Corrigendum.

PMID- 29220620
TI  - Mediating Peer Teaching for Learning Games: An Action Research Intervention
      Across Three Consecutive Sport Education Seasons.
AB  - PURPOSE: The purpose of this study was to provide an integrated analysis of a
      teacher's peer-teaching mediation strategies, the student-coaches' instruction,
      and the students' gameplay development across 3 consecutive seasons of sport
      education. METHOD: Twenty-six 7th-grade students participated in 3 consecutive
      sport education seasons of invasion games (basketball, handball, and soccer). The
      research involved 3 action research cycles, 1 per season, and each cycle included
      the processes of planning, acting and monitoring, reflecting, and fact finding.
      Data collection consisted of videotape and audiotape records of all 47 lessons, a
      reflective field diary kept by the first author in the role of teacher
      researcher, and a total of 24 semistructured focus-group interviews.
      Trustworthiness criteria for assuring the quality of qualitative research
      included extensive data triangulation, stakeholders' crosschecking, and
      collaborative interpretational analysis. RESULTS: Through the application of
      systematic preparation strategies, student-coaches were able to successfully
      conduct team instruction that resulted in students' tactical development and
      improved performance. Aspects such as the study of predominant configurations of
      players' gameplay and similar tactical principles across games within the same
      category prevented a setback in the complexity of the learning content addressed
      at the beginning of each season. Players also showed an increasing ability to
      adapt gameplay to game conditions. CONCLUSIONS: While sport education has the
      capacity to develop competent players, different levels of teacher guidance and
      learners' instructional responsibility are necessary when teaching tactics.

PMID- 29220623
TI  - The Aging Well through Interaction and Scientific Education (AgeWISE) Program.
AB  - OBJECTIVE: We conducted a randomized controlled trial of the Aging Well through
      Interaction and Scientific Education (AgeWISE) program, a 12-week manualized
      cognitive rehabilitation program designed to provide psychoeducation to older
      adults about the aging brain, lifestyle factors associated with successful brain
      aging, and strategies to compensate for age related cognitive decline. METHODS:
      Forty-nine cognitively intact participants >= 60 years old were randomly assigned
      to the AgeWISE program (n = 25) or a no-treatment control group (n = 24).
      Questionnaire data were collected prior to group assignment and post
      intervention. Two-factor repeated-measures analyses of covariance (ANCOVAs) were
      used to compare group outcomes. RESULTS: Upon completion, participants in the
      AgeWISE program reported increases in memory contentment and their sense of
      control in improving memory; no significant changes were observed in the control
      group. Surprisingly, participation in the group was not associated with
      significant changes in knowledge of memory aging, perception of memory ability,
      or greater use of strategies. CONCLUSIONS: The AgeWISE program was successfully
      implemented and increased participants' memory contentment and their sense of
      control in improving memory in advancing age. CLINICAL IMPLICATIONS: This study
      supports the use of AgeWISE to improve perspectives on healthy cognitive aging.

PMID- 29220628
TI  - Autobiographical Narration as a Tool for the Empowerment of Older Adults'
      Subjective and Psychological Wellbeing in Nursing Homes.
AB  - OBJECTIVES: Conceiving narration as a resource to promote older people's
      wellbeing, the present work aimed to implement a narrative-based intervention to
      empower the subjective and psychological wellbeing of older adults living in
      nursing homes. METHODS: Twenty-one nursing-home residents took part in a
      narrative training experience consisting of three weekly interview sessions.
      During each interview, a psychologist helped the participants to construct an
      autobiographical narrative about their present life in the nursing home based on
      a Deconstruction-Reconstruction technique. Subjective and psychological wellbeing
      variables were assessed before and after the intervention. RESULTS: Subjective
      but not psychological wellbeing increased over the course of the intervention.
      The participants reported to appreciate the intervention. CONCLUSIONS: Although
      preliminary, the results suggest that brief narrative training based on narrative
      therapy can positively affect nursing-home residents' subjective wellbeing.
      CLINICAL IMPLICATIONS: Brief narrative interventions implementing deconstruction
      reconstruction techniques are feasible for long-term care residents.

PMID- 29220627
TI  - Neuropsychological Functioning in Older Adults with Mild Cognitive Impairment and
      Insomnia Randomized to CBT-I or Control Group.
AB  - OBJECTIVES: Improving the sleep of older adults with mild cognitive impairment
      (MCI) represents a first step in discovering whether interventions directed at
      modifying this risk factor also have the potential to alter the cognitive decline
      trajectory. METHODS: A six-session, adapted version of a cognitive behavioral
      therapy for insomnia (CBT-I) was administered to older adults (N = 28; 14 per
      group) with MCI across two residential facilities. Participants were randomly
      assigned to either the sleep intervention or an active control group and
      completed a neuropsychological battery at three time points (e.g., baseline-T1,
      post-intervention-T2, 4 month follow-up-T3). RESULTS: Results showed a
      significant improvement in sleep and a change (p < .05) on a key measure of
      executive functioning sub task of inhibition (Condition 3 of D-KEF Color-Word
      Interference Test), a positive trend on the inhibition-switching task (p < .10;
      Condition 4 of D-KEF Color-Word Interference Test), an no change in a measure of
      verbal memory (HVLT-R Delayed Recall) compared with the active control group.
      CONCLUSIONS: CBT-I is a nonpharmacological intervention that has the potential to
      cognitively benefit individuals with MCI suffering from comorbid insomnia.
      CLINICAL IMPLICATIONS: Results suggest that a non-pharmacological intervention to
      improve sleep in older adults with MCI also improve cognitive functioning.
      Further exploration of the mechanisms underlying these improvements is warranted.

PMID- 29220629
TI  - Personal emergency alarms: do health outcomes differ for purchasers and
      nonpurchasers?
AB  - The objective of this study was to assess whether purchasing a personal alarm
      service makes a difference in a range of health outcomes for community dwelling
      older adults. The prospective cohort study involved 295 individuals for whom data
      on emergencies experienced at home were collected over a period of 12 months.
      Purchasers of alarms, compared to nonpurchasers, benefitted in terms of feeling
      more safe and secure and being more active around their home. Outcomes
      experienced after an emergency were similar for both groups with no differences
      found in terms of time spent on floor, or hospitalizations.

PMID- 29220631
TI  - Economic Myths Regarding Gay Men and Lesbians.
AB  - The present research was aimed at developing a measure of economic myths
      regarding the gay community. Using undergraduate (N = 332) and Amazon Mechanical
      Turk (N = 212) samples, Study 1 resulted in a 6-item unidimensional and reliable
      measure, the Economic Myths Regarding Gays Scale (EMGS), that was minimally
      related to other measures of sexual orientation attitudes. Study 2 (N = 210
      undergraduates) found that endorsement of economic myths was associated with
      system justification beliefs that economic inequalities were natural and due to
      individual merit; however, general attitudes toward gays showed no such
      relationships. Study 3 (N = 85 undergraduates) found that unlike general
      stereotyping, economic myth endorsement increased in response to induced economic
      threat from the gay community. Collectively, the present research suggests that
      the EMGS is largely distinct from other measures of attitudes and stereotyping
      and can potentially widen research regarding sexual orientation.

PMID- 29220630
TI  - Aging women and men in the medical profession: The effect of gender and marital
      status on successful aging and retirement intent in Australian doctors.
AB  - Despite increasing interest from the medical profession in aging and retirement,
      we know little about effects of gender, marital status, and cohort on aging
      within the profession. We surveyed 1,048 Australian doctors from "younger" (55
      64) and "older" (65-89) cohorts, investigating gender and marital effects on
      perceptions of successful aging, career, and retirement intent. Women intend to
      retire earlier. Younger cohort and married women more frequently viewed their
      career as a calling, while women in general, and single women more frequently,
      endorsed personal successful aging more than men. Broader understanding of the
      different experiences of aging for men and women doctors is needed.

PMID- 29220636
TI  - From the Editor.

PMID- 29220635
TI  - Letter to the editor.

PMID- 29220634
TI  - Justification-Suppression and Normative Window of Prejudice as Determinants of
      Bias Toward Lesbians, Gays, and Bisexual Adoption Applicants.
AB  - Despite gains in equality for lesbians, gays, and bisexuals (LGB), these couples
      still face discrimination in adoption scenarios. Guided by the normative window
      of prejudice and the justification-suppression model, participants read about a
      suitable or unsuitable couple applying to adopt a child. Participants indicated
      whether the couple should be allowed to adopt the child and how committed the
      couple is to being parents. Heterosexuals were perceived as less committed
      parents compared to LGB parents; sexual orientation was not related to adoption
      decisions. There was a significant interaction between sexual orientation and
      suitability for perceptions of commitment to parenting: in the suitable
      condition, heterosexuals were perceived as less committed parents compared to
      gays; in the unsuitable condition, heterosexuals were perceived as less committed
      parents compared to bisexuals. This interaction was nonsignificant for adoption
      decisions. Future research should determine if these findings relate to other
      sexual orientations or gender identities.

PMID- 29220632
TI  - Immunohistochemical Localization of Fibrinogen C Domain Containing 1 on
      Epithelial and Mucosal Surfaces in Human Tissues.
AB  - Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane receptor that binds
      chitin and other acetylated compounds with high affinity. FIBCD1 has previously
      been shown to be present in the epithelium of the gastrointestinal tract. In the
      present study, we performed a detailed analysis of normally structured human
      tissues for the expression of FIBCD1 by quantitative PCR and
      immunohistochemistry. We find that FIBCD1 is expressed in epithelial cells
      derived from all three germ layers. Endodermal-derived epithelial cells
      throughout the gastrointestinal tract and the respiratory system showed high
      expression of FIBCD1 and also mesodermal-derived cells in the genitourinary
      system and ectodermal-derived epidermis and sebaceous glands cells expressed
      FIBCD1. In some columnar epithelial cells, for example, in the salivary gland and
      gall bladder, the FIBCD1 expression was clearly polarized with strong apical
      reaction, while other columnar cells, for example, in small and large intestine
      and in bronchi, the staining was equally strong apically and basolaterally. In
      keratinocytes in skin, tongue, and oral cavity, the FIBCD1 staining was granular.
      This expression pattern together with the known binding properties supports that
      FIBCD1 plays a role in innate immunity in the skin and at mucosal surfaces.

PMID- 29220633
TI  - Developing Adaptive Treatment Strategies to Address Suicidal Risk in College
      Students: A Pilot Sequential, Multiple Assignment, Randomized Trial (SMART).
AB  - This pilot study investigated the potential to utilize adaptive treatment
      strategies for treating moderate to severe suicidal risk among college students.
      This article will describe the unique study design and report on feasibility and
      acceptability findings. A 2-stage Sequential Multiple Assignment Randomized Trial
      (SMART) was conducted: In Stage 1, 62 suicidal college students were randomized
      to either a suicide-focused or a treatment-as-usual condition (4-8 weeks). Those
      deemed insufficient responders were re-randomized to one of two Stage 2
      interventions-both suicide-focused but one comprehensive and multimodal and the
      other flexible and theoretically agnostic (4-16 additional weeks). Recruitment
      rates were high, treatment dropout levels were lower than expected for the
      setting, study dropouts were rare, and counselors were able to deliver suicide
      focused approaches with fidelity. Treatment satisfaction was high among clients
      and moderately high among counselors. Findings from this pilot show that a SMART
      is highly feasible and acceptable to suicidal college students, counselors, and
      campuses.

PMID- 29220640
TI  - Invariants in probabilistic reasoning.
AB  - Recent research has identified three invariants or identities that appear to hold
      in people's probabilistic reasoning: the QQ identity, the addition law identity,
      and the Bayes rule identity (Costello and Watts, 2014, 2016a, Fisher and Wolfe,
      2014, Wang and Busemeyer, 2013, Wang et al., 2014). Each of these identities
      represent specific agreement with the requirements of normative probability
      theory; strikingly, these identities seem to hold in people's judgements despite
      the presence of strong and systematic biases against the requirements of
      normative probability theory in those very same judgements. These results suggest
      that the systematic biases seen in people's probabilistic reasoning follow
      mathematical rules: for these particular identities, these rules cause an overall
      cancellation of biases and so produce agreement with normative requirements. We
      assess two competing mathematical models of probabilistic reasoning (the
      'probability theory plus noise' model and the 'quantum probability' model) in
      terms of their ability to account for this pattern of systematic biases and
      invariant identities.

PMID- 29220644
TI  - Structure and genetics of the O-specific polysaccharide of Escherichia coli O27.
AB  - The O-specific polysaccharide (O-antigen) is a part of the lipopolysaccharide on
      the cell surface of Gram-negative bacteria. The O-polysaccharide was obtained by
      mild acid hydrolysis of the lipopolysaccharide of Escherichia coli O27 and
      studied by sugar analysis and Smith degradation along with 1H and 13C NMR
      spectroscopy. The following structure of the branched hexasaccharide repeating
      unit was established, which is unique among known structures of bacterial
      polysaccharides:where GlcA is non-stoichiometrically O-acetylated at position 3
      (~22%) or 4 (~37%). Functions of genes in the O-antigen gene cluster of E. coli
      O27 were tentatively assigned by comparison with sequences in the available
      databases and found to be consistent with the O-polysaccharide structure.

PMID- 29220645
TI  - The value of a learning needs analysis to establish educational priorities in a
      new clinical workforce.
AB  - A learning needs analysis was undertaken in a newly formed workforce. The goal of
      the learning needs analysis was to establish both the skill set and educational
      needs in the nursing workforce prior to moving to a new purpose built facility.
      The results would then enable nurse educators to develop, plan and deliver
      appropriate educational strategies. Staff (73%) completed an online survey; the
      results were collated and analysed. The results of the learning needs analysis
      suggested an experienced workforce that had great capacity to care for children
      across a wide spectrum of acute clinical needs. Interestingly the results of the
      learning needs analysis conflicted with the clinical reality. To investigate
      possible reasons for this difference we conducted a focus group session with
      nurse educators. The focus group findings highlighted the significance of change
      and how that impacted on the clinical capacity of experienced staff. We concluded
      that the results of the learning needs analysis were representative however they
      needed careful interpretation in the context of substantial change.

PMID- 29220643
TI  - Polygenic risk for alcohol consumption and its association with alcohol-related
      phenotypes: Do stress and life satisfaction moderate these relationships?
AB  - BACKGROUND: Genetic and environmental factors contribute about equally to alcohol
      related phenotypes in adulthood. In the present study, we examined whether more
      stress at home or low satisfaction with life might be associated with heavier
      drinking or more alcohol-related problems in individuals with a high genetic
      susceptibility to alcohol use. METHODS: Information on polygenic scores and
      drinking behavior was available in 6705 adults (65% female; 18-83 years)
      registered with the Netherlands Twin Register. Polygenic risk scores (PRSs) were
      constructed for all subjects based on the summary statistics of a large genome
      wide association meta-analysis on alcohol consumption (grams per day). Outcome
      measures were quantity of alcohol consumption and alcohol-related problems
      assessed with the Alcohol Use Disorders Identification Test (AUDIT). Stress at
      home and life satisfaction were moderating variables whose significance was
      tested by Generalized Estimating Equation analyses taking familial relatedness,
      age and sex into account. RESULTS: PRSs for alcohol were significantly associated
      with quantity of alcohol consumption and alcohol-related problems in the past
      year (R2=0.11% and 0.10% respectively). Participants who reported to have
      experienced more stress in the past year and lower life satisfaction, scored
      higher on alcohol-related problems (R2=0.27% and 0.29 respectively), but not on
      alcohol consumption. Stress and life satisfaction did not moderate the
      association between PRSs and the alcohol outcome measures. CONCLUSIONS: There
      were significant main effects of polygenic scores and of stress and life
      satisfaction on drinking behavior, but there was no support for PRS-by-stress or
      PRS-by-life satisfaction interactions on alcohol consumption and alcohol-related
      problems.

PMID- 29220639
TI  - Early lumbar puncture and risk of intraventricular hemorrhage in very low birth
      weight infants.
AB  - BACKGROUND: Lumbar puncture (LP) is the gold standard for diagnosing meningitis;
      however it is unknown whether early LP (<=3days of life) is associated with
      increased risk of intraventricular hemorrhage (IVH) in very low birth weight
      (VLBW) infants. OBJECTIVE: To determine whether early LP in VLBW infants is
      associated with severe IVH. METHODS: VLBW infants from a cohort of 1,158,789
      infants discharged from 382 neonatal intensive care units (1997-2015) were
      enrolled. EXCLUSION CRITERIA: infants with major congenital anomalies, outborns,
      died/transferred prior to day of life 3, and those who had an LP performed only
      after day of life 3. Logistic regression was used to determine the association
      between early LP and the incidence of severe IVH (IVH grades 3/4) by 28days of
      life for each day of life from day 0 (birth) to day 3, adjusting for clinical
      covariates. RESULTS: 106,461 infants were included: 754 received an LP on Day-0,
      640 on Day-1, 559 on Day-2 and 483 on Day-3. Severe IVH occurred in 4%
      (4130/104,025) of the infants in the no LP group and 9% (217/2436) of the LP
      group. Severe IVH was higher for infants with early LP: adjusted OR (95%
      confidence interval)=2.64 (1.96-3.54) on Day-0; 2.21 (1.61-3.04) on Day-1; 1.55
      (1.03-2.34) on Day-2; and 2.25 (1.50-3.38) on Day-3. CONCLUSIONS: Early LP was
      associated with severe IVH in VLBW infants by 28days of life. LP is either a
      surrogate for an unrecognized factor or is itself associated with an increased
      risk of IVH.

PMID- 29220648
TI  - Encoding Allostery in mTOR Signaling: The Structure of the Rag GTPase/Ragulator
      Complex.
AB  - In this issue of Molecular Cell, Su et al. (2017) describe the structure of the
      Rag/Ragulator complex, a key relay in nutrient sensing by mTOR. The structure
      sheds new light on how signals are conveyed from the lysosome to mTOR.

PMID- 29220641
TI  - Coronary vascular disease event risk and metabolic syndrome prevalence in
      patients enrolled in an assertive treatment community program.
AB  - OBJECTIVE: To examine the risk of coronary vascular disease event (CVDE) and the
      prevalence metabolic syndrome (MS) and its cardiovascular risk factors (CVRF) in
      patients with severe mental illnesses enrolled in an assertive treatment
      community program (ATC) in Spain. METHOD: We carried out a cross-sectional
      descriptive study with all of the patients included in an ATC program in 2016 in
      a health area with 547,328 inhabitants in Galicia, Spain. We identified the CVRF
      in all the individuals, and calculated MS and 10-year CVDE. We also compared the
      prevalence of all traits in our cohort and the general population. RESULTS: The
      10-year median of coronary vascular disease event (CVDE10) was 8.4%. The
      percentage of individuals with high CVDE10 (>5%) was 41.2% The CVDE10 median was
      higher in men than women (10.5% vs 5.1%, p<0.001). MS was detected in 50% of
      patients without differences between men and women (51.2% vs 48.2%). A prevalence
      of 68% was found for smoking, 55% for dyslipidemia, 47% for obesity, 29% for
      impaired glucose metabolism, and 38% for hypertension. Women showed a higher
      prevalence of obesity measured by elevated waist circumference (88.9% vs 55.6%,
      p=0.003). Men showed a higher prevalence of arterial hypertension (46.6% vs
      22.2%, p=0.0001). CONCLUSIONS: The SMD Patients enrolled in ATC programs had a
      1.5-times higher prevalence of MS and 8 times higher CVDE10 than those reported
      in the general population. Individual CVRF were also higher in the SMD patients.
      Prevention, early detection, and comprehensive treatment are important issues for
      patients with severe mental illnesses.

PMID- 29220647
TI  - SnapShot: Lysine Methylation beyond Histones.
AB  - Lysine methylation is a prevalent post-translational modification (PTM) used by
      the cell to reversibly regulate protein function. Although it has been
      extensively studied in the context of histones and the associated chromatin, the
      remaining methyllysine proteome remains largely unexplored. This SnapShot
      provides an overview of the current state of lysine methylation research and its
      emergence as a dynamic PTM occurring on histone and non-histone proteins.

PMID- 29220642
TI  - Substance use patterns associated with recent exposure to fentanyl among people
      who inject drugs in Vancouver, Canada: A cross-sectional urine toxicology
      screening study.
AB  - INTRODUCTION: Vancouver, Canada is experiencing an opioid overdose crisis where
      fentanyl, a potent, synthetic opioid contaminating the illicit drug supply, has
      been detected in the majority of fatal overdose cases. Despite its growing
      presence throughout North America, few studies have characterized exposure to
      fentanyl among people who use illicit drugs (PWUD). We sought to identify the
      prevalence and correlates of fentanyl exposure among PWUD in Vancouver. METHODS:
      Data were derived from cohort studies of PWUD in Vancouver. In June-October 2016,
      we administered multi-panel urine drug screens (UDS) to detect recent exposure to
      fentanyl and eight other substances. Multivariable logistic regression was used
      to identify substance use patterns associated with recent fentanyl exposure among
      participants who injected drugs in the past six months (PWID). RESULTS: Among 669
      PWUD including 250 (37.4%) females and 452 (67.6%) PWID, 97 (14.5%) tested
      positive for fentanyl. All these individuals also tested positive for other
      substances, most commonly for morphine/heroin (89.9%),
      amphetamine/methamphetamine (75.3%) and cocaine (74.2%). A fentanyl detection
      rate was significantly higher among PWID (19.7%) compared to non-injection drug
      users (3.9%) (p<0.001). In multivariable analyses, younger age (adjusted odds
      ratio [AOR]: 0.96) and testing positive for morphine/heroin (AOR: 6.73),
      buprenorphine (AOR: 4.25), amphetamine/methamphetamine (AOR: 3.26), cocaine (AOR:
      2.92) and cannabis (AOR: 0.52) remained independently associated with fentanyl
      exposure (all p<0.05). CONCLUSION: With one in five PWID being exposed to
      fentanyl, there is an urgent need to design and scale up interventions to reduce
      overdose risk, including a range of opioid agonist therapies.

PMID- 29220646
TI  - Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in
      Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq.
AB  - Massively parallel single-cell RNA sequencing can precisely resolve cellular
      diversity in a high-throughput manner at low cost, but unbiased isolation of
      intact single cells from complex tissues such as adult mammalian brains is
      challenging. Here, we integrate sucrose-gradient-assisted purification of nuclei
      with droplet microfluidics to develop a highly scalable single-nucleus RNA-seq
      approach (sNucDrop-seq), which is free of enzymatic dissociation and nucleus
      sorting. By profiling ~18,000 nuclei isolated from cortical tissues of adult
      mice, we demonstrate that sNucDrop-seq not only accurately reveals neuronal and
      non-neuronal subtype composition with high sensitivity but also enables in-depth
      analysis of transient transcriptional states driven by neuronal activity, at
      single-cell resolution, in vivo.

PMID- 29220649
TI  - Loud and Clear Epitranscriptomic m1A Signals: Now in Single-Base Resolution.
AB  - In this issue of Molecular Cell, Li et al. (2017) map N1-methyladenosine (m1A)
      with base precision, parsing the methylome into subsets differing in location,
      sequence-structure features, and catalyzing enzymes, thereby aiding functional
      investigation.

PMID- 29220650
TI  - The Haystack Is Full of Needles: Technology Rescues Sugars!
AB  - The recent paper by Stadlmann et al. (2017) provides a novel algorithm for
      glycoproteomics in which complex glycopeptides can be identified in complex
      mixtures to aid in characterizing both the site of glycosylation and the glycan
      structure.

PMID- 29220659
TI  - Organizing Organoids: Stem Cells Branch Out.
AB  - In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a
      carefully optimized method for making a branch-competent ureteric bud, a tissue
      fundamental to kidney development, from mouse embryonic stem cells and human
      induced pluripotent stem cells. The work illuminates embryology and has important
      implications for making more realistic kidney organoids.

PMID- 29220660
TI  - Plasticity in Olfactory Epithelium: Is It a Sniffer or Shape Shifter?
AB  - Precise lineage trajectories and the cellular sources that contribute to
      regeneration after injury are largely unknown in many tissues. In this issue of
      Cell Stem Cell, Gadye et al. (2017) and Lin et al. (2017) show that olfactory
      epithelial cells transit through unique and unfamiliar paths of differentiation
      and undergo lineage reversion, respectively, during regeneration.

PMID- 29220663
TI  - Intermittent Reprogramming: A Breath of Fresh Air for Lung Regeneration.
AB  - Recently in Stem Cell Reports, Guo et al. (2017) adopted an intermittent
      reprogramming strategy to generate "induced Progenitor-Like (iPL)" cells, which
      can maintain lineage commitment while undergoing controlled expansion. The iPLCs
      were successfully engrafted into a damaged airway, highlighting this significant
      advancement for regenerative medicine strategies in the lung.

PMID- 29220662
TI  - iPSC Reprogramming Is Not Just an Open and Shut Case.
AB  - What exactly happens to chromatin as cells undergo an identity change? In this
      issue of Cell Stem Cell, Li et al. (2017) and Knaupp et al. (2017) offer new
      insights by mapping in exquisite detail chromatin accessibility dynamics as mouse
      embryonic fibroblasts are reprogrammed into induced pluripotent stem cells.

PMID- 29220661
TI  - Saving Stem Cells after Stress.
AB  - Inflammatory signals can activate hematopoietic stem cells (HSCs), but how HSCs
      regain quiescence after stress is unclear. In this issue of Cell Stem Cell, Chen
      et al. (2017) delineate an elegant histamine-dependent feedback mechanism through
      which myeloid bone marrow cells restore quiescence of myeloid-biased HSCs, with
      implications for blood disorders, aging, and immunity.

PMID- 29220664
TI  - Locked and Loaded: Inflammation Training Prepares Skin Epithelial Stem Cells for
      Trauma.
AB  - Memory of a trauma and how to cope with it is useful for acting rapidly in the
      event of a second traumatic incident. Recently, Naik et al. (2017) reported in
      Nature that skin epithelial stem cells have this ability by maintaining long-term
      chromatin features acquired during the first assault.

PMID- 29220651
TI  - Replication Fork Reversal: Players and Guardians.
AB  - Replication fork reversal is a rapidly emerging and remarkably frequent mechanism
      of fork stabilization in response to genotoxic insults. Here, we summarize recent
      findings that uncover key molecular determinants for reversed fork formation and
      describe how the homologous recombination factors BRCA1, BRCA2, and RAD51 protect
      these structures from extended nucleolytic degradation.

PMID- 29220655
TI  - AID and Reactive Oxygen Species Can Induce DNA Breaks within Human Chromosomal
      Translocation Fragile Zones.
AB  - DNA double-strand breaks (DSBs) occurring within fragile zones of less than 200
      base pairs account for the formation of the most common human chromosomal
      translocations in lymphoid malignancies, yet the mechanism of how breaks occur
      remains unknown. Here, we have transferred human fragile zones into S. cerevisiae
      in the context of a genetic assay to understand the mechanism leading to DSBs at
      these sites. Our findings indicate that a combination of factors is required to
      sensitize these regions. Foremost, DNA strand separation by transcription or
      increased torsional stress can expose these DNA regions to damage from either the
      expression of human AID or increased oxidative stress. This damage causes DNA
      lesions that, if not repaired quickly, are prone to nuclease cleavage, resulting
      in DSBs. Our results provide mechanistic insight into why human neoplastic
      translocation fragile DNA sequences are more prone to enzymes or agents that
      cause longer-lived DNA lesions.

PMID- 29220653
TI  - A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling
      Oncogene.
AB  - DNA damage triggers chromatin remodeling by mechanisms that are poorly
      understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts
      chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction.
      We show that the interaction of the ALC1 macrodomain with the ATPase module
      mediates auto-inhibition. PARP1 activation suppresses this inhibitory
      interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose
      (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and
      synthetic allosteric effector that abrogates ATPase-macrodomain interactions,
      promotes an ungated conformation, and activates the remodeler's ATPase. ALC1
      fragments lacking the regulatory macrodomain relax chromatin in vivo without
      requiring PARP1 activation. Further, the ATPase restricts the macrodomain's
      interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants
      disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show
      that the NAD+-metabolite and nucleic acid PAR triggers ALC1 to drive chromatin
      relaxation. Modular allostery in this oncogene tightly controls its robust, DNA
      damage-dependent activation.

PMID- 29220669
TI  - Modulation of dietary folate with age confers selective hepatocellular epigenetic
      imprints through DNA methylation.
AB  - The present study has been designed to determine the effect of folate modulation
      (deficiency/supplementation) with aging on the promoter methylation of tumor
      suppressor and proto-oncogenes to understand the underlying mechanism of
      epigenetic alterations. Folate deficiency was induced for 3 and 5 months in
      weanling, young and adult groups, and after 3 months of folate deficiency, they
      were repleted with physiological folate (2 mg/kg diet) and folate
      oversupplementation (8 mg/kg diet) for another 2 months. The methylation facet in
      the present study revealed that the combined effect of folate deficiency and
      aging decreased the methylation index. Folate deficiency with age resulted in the
      up-regulation of proto-oncogenes (C-MYC and C-JUN) and cell cycle regulator gene
      Cyclin E as a result of promoter hypomethylation. However, in case of tumor
      suppressor genes (p53, p15ink4b and p16ink4a), the expression levels were found
      to be decreased at transcriptional level due to promoter hypermethylation. Upon
      repletion with physiological folate and folate oversupplementation, we found down
      regulation of proto-oncogenes and up-regulation of tumor suppressor genes as a
      result of promoter hypermethylation and hypomethylation, respectively.
      Deregulation of these important genes due to folate deficiency may contribute
      toward the pathogenesis at cellular level.

PMID- 29220670
TI  - QM/MM modeling of the hydrolysis and transfructosylation reactions of
      fructosyltransferase from Aspergillus japonicas, an enzyme that produces
      prebiotic fructooligosaccharide.
AB  - Fructosyltransferases (FTs) act on sucrose by cleaving the beta-(2->1) linkage,
      releasing glucose, and then transferring the fructosyl group to an acceptor
      molecule. These enzymes are capable of producing prebiotic fructooligosaccharides
      (FOSs) that are of industrial interest. While several FOS-synthesizing enzymes
      FTs have been investigated, their catalytic mechanism is not yet fully
      understood, especially the molecular details of how FOS are enzymatically
      synthesized from sucrose. Here, we present a comparative quantum
      mechanics/molecular mechanics (QM/MM) study on the hydrolysis and
      transfructosylation reactions catalyzed by A. japonicus FT using sucrose as donor
      and acceptor substrates. It is shown that the hydrolysis and transfructosylation
      reactions of the enzyme seem to be competitive with similar potential energy
      profiles. For all studied reaction steps, the fructosyl ring bound in the -1
      position was observed to have a 4E conformation in the oxocarbonium ion-like
      transition state. Based on the SCC-DFTB/MM simulations of sucrose complexes of
      wildtype and D191A mutant FT, Asp191 is shown to be responsible for the
      productive sugar conformation (at subsite -1) required for catalysis. A key
      interaction, Asp119?nucleophile?1-OH (substrate), is proposed to facilitate the
      formation of fructosyl-enzyme intermediate. This is the first computational study
      for understanding the FOS synthesis process, and it can be applicable to related
      FOS-synthesizing enzymes.

PMID- 29220652
TI  - Mechanistic Insights into Autoinhibition of the Oncogenic Chromatin Remodeler
      ALC1.
AB  - Human ALC1 is an oncogene-encoded chromatin-remodeling enzyme required for DNA
      repair that possesses a poly(ADP-ribose) (PAR)-binding macro domain. Its
      engagement with PARylated PARP1 activates ALC1 at sites of DNA damage, but the
      underlying mechanism remains unclear. Here, we establish a dual role for the
      macro domain in autoinhibition of ALC1 ATPase activity and coupling to nucleosome
      mobilization. In the absence of DNA damage, an inactive conformation of the
      ATPase is maintained by juxtaposition of the macro domain against predominantly
      the C-terminal ATPase lobe through conserved electrostatic interactions.
      Mutations within this interface displace the macro domain, constitutively
      activate the ALC1 ATPase independent of PARylated PARP1, and alter the dynamics
      of ALC1 recruitment at DNA damage sites. Upon DNA damage, binding of PARylated
      PARP1 by the macro domain induces a conformational change that relieves
      autoinhibitory interactions with the ATPase motor, which selectively activates
      ALC1 remodeling upon recruitment to sites of DNA damage.

PMID- 29220666
TI  - Chromatin Accessibility Dynamics during iPSC Reprogramming.
AB  - Cell-fate decisions remain poorly understood at the chromatin level. Here, we map
      chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC
      seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in
      chromatin states shifting from open to closed (OC) and closed to open (CO), with
      an initial burst of OC and an ending surge of CO. The OC loci are largely
      composed of genes associated with a somatic fate, while the CO loci are
      associated with pluripotency. Factors/conditions known to impede reprogramming
      prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for
      OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin
      closing. Sap30, a Sin3A corepressor complex component, is required for the OC
      shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal
      a chromatin accessibility logic during reprogramming that may apply to other cell
      fate decisions.

PMID- 29220667
TI  - Transient and Permanent Reconfiguration of Chromatin and Transcription Factor
      Occupancy Drive Reprogramming.
AB  - Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces
      changes in genome architecture reflective of the embryonic stem cell (ESC) state.
      However, only a small minority of cells typically transition to pluripotency,
      which has limited our understanding of the process. Here, we characterize the DNA
      regulatory landscape during reprogramming by time-course profiling of isolated
      sub-populations of intermediates poised to become iPSCs. Widespread
      reconfiguration of chromatin states and transcription factor (TF) occupancy
      occurs early during reprogramming, and cells that fail to reprogram partially
      retain their original chromatin states. A second wave of reconfiguration occurs
      just prior to pluripotency acquisition, where a majority of early changes revert
      to the somatic cell state and many of the changes that define the pluripotent
      state become established. Our comprehensive characterization of reprogramming
      associated molecular changes broadens our understanding of this process and sheds
      light on how TFs access and change the chromatin during cell-fate transitions.

PMID- 29220654
TI  - A Unique ISR Program Determines Cellular Responses to Chronic Stress.
AB  - The integrated stress response (ISR) is a homeostatic mechanism induced by
      endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global
      protein synthesis and increased uORF mRNA translation are followed by
      normalization of protein synthesis. Here, we report a dramatically different
      response during chronic ER stress. This chronic ISR program is characterized by
      persistently elevated uORF mRNA translation and concurrent gene expression
      reprogramming, which permits simultaneous stress sensing and proteostasis. The
      program includes PERK-dependent switching to an eIF3-dependent translation
      initiation mechanism, resulting in partial, but not complete, translational
      recovery, which, together with transcriptional reprogramming, selectively
      bolsters expression of proteins with ER functions. Coordination of
      transcriptional and translational reprogramming prevents ER dysfunction and
      inhibits "foamy cell" development, thus establishing a molecular basis for
      understanding human diseases associated with ER dysfunction.

PMID- 29220668
TI  - Nonmedical prescription opioids and pathways of drug involvement in the US:
      Generational differences.
AB  - BACKGROUND: This study sought to specify (1) the position of nonmedical
      prescription opioids (NMPO) in drug initiation sequences among Millennials (1979
      96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and
      racial/ethnic differences in sequences among Millennials. METHODS: Data are from
      the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified
      statistically significant drug initiation sequences involving alcohol/cigarettes,
      marijuana, NMPO, cocaine, and heroin using a novel method distinguishing
      significant sequences from patterns expected only due to correlations induced by
      common liability among drugs. RESULTS: Alcohol/cigarettes followed by marijuana
      was the most common sequence. NMPO or cocaine use after marijuana, and heroin use
      after NMPO or cocaine, differed by generation. Among successively younger
      generations, NMPO after marijuana and heroin after NMPO increased. Millennials
      were more likely to initiate NMPO than cocaine after marijuana; Generation X and
      Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more
      likely than Generation X and Baby Boomers to use heroin after NMPO (hazards
      ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to
      start heroin after both NMPO and cocaine than either alone. Sequences were
      similar by gender. Fewer paths were significant among African-Americans.
      CONCLUSIONS: NMPOs play a more prominent role in drug initiation sequences among
      Millennials than prior generations. Among Millennials, NMPO use is more likely
      than cocaine to follow marijuana use. In all generations, transition to heroin
      from NMPO significantly occurs only when both NMPO and cocaine have been used.
      Delineation of drug sequences suggests optimal points in development for
      prevention and treatment efforts.

PMID- 29220658
TI  - Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q
      Production.
AB  - Mitoproteases are becoming recognized as key regulators of diverse mitochondrial
      functions, although their direct substrates are often difficult to discern.
      Through multi-omic profiling of diverse Saccharomyces cerevisiae mitoprotease
      deletion strains, we predicted numerous associations between mitoproteases and
      distinct mitochondrial processes. These include a strong association between the
      mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis-a
      pathway essential for mitochondrial respiration. Through Edman sequencing and in
      vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the
      N terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves
      its stability. A single mutation to the Oct1p recognition motif in Coq5p
      disrupted its processing in vivo, leading to CoQ deficiency and respiratory
      incompetence. This work defines the Oct1p processing of Coq5p as an essential
      post-translational event for proper CoQ production. Additionally, our data
      visualization tool enables efficient exploration of mitoprotease profiles that
      can serve as the basis for future mechanistic investigations.

PMID- 29220656
TI  - MPK1/SLT2 Links Multiple Stress Responses with Gene Expression in Budding Yeast
      by Phosphorylating Tyr1 of the RNAP II CTD.
AB  - The RNA polymerase II largest subunit C-terminal domain consists of repeated
      YSPTSPS heptapeptides. The role of tyrosine-1 (Tyr1) remains incompletely
      understood, as, for example, mutating all Tyr1 residues to Phe (Y1F) is lethal in
      vertebrates but a related mutant has only a mild phenotype in S. pombe. Here we
      show that Y1F substitution in budding yeast resulted in a strong slow-growth
      phenotype. The Y1F strain was also hypersensitive to several different cellular
      stresses that involve MAP kinase signaling. These phenotypes were all linked to
      transcriptional changes, and we also identified genetic and biochemical
      interactions between Tyr1 and both transcription initiation and termination
      factors. Further studies uncovered defects related to MAP kinase I (Slt2)
      pathways, and we provide evidence that Slt2 phosphorylates Tyr1 in vitro and in
      vivo. Our study has thus identified Slt2 as a Tyr1 kinase, and in doing so
      provided links between stress response activation and Tyr1 phosphorylation.

PMID- 29220672
TI  - International Humanitarian Law: The legal framework for humanitarian forensic
      action.
AB  - In armed conflicts, death is not an exceptional occurrence, but becomes the rule
      and occurs on a daily basis. Dead bodies are sometimes despoiled, mutilated,
      abandoned without any funeral rite and without a decent burial. Unidentified
      remains may be counted by hundreds or thousands. As a result, families look for
      years for missing relatives, ignorant of the fate of their loved ones.
      International Humanitarian Law, also called the laws of war or the law of armed
      conflict, is an international law branch, which has been developed to regulate
      and, as far as possible, to humanize armed conflicts. It contains a number of
      clear and concrete obligations incumbent to belligerent parties on the management
      of dead bodies, which provide the legal framework for humanitarian forensic
      action. The purpose of this article is to present, in a simple and concise
      manner, these rules with a view to extrapolate some key legal principles, such as
      the obligation to respect the dignity of the dead or the right to know the fate
      of relatives, which shall guide anyone dealing with human remains.

PMID- 29220657
TI  - hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb
      Mediated Chromosomal Silencing.
AB  - The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome
      silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated
      by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119
      ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However,
      the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not
      understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a
      600 nt sequence encompassing the Xist B-repeat element. Deletion of XR-PID
      abolishes Xist-dependent Polycomb recruitment, in turn abrogating Xist-mediated
      gene silencing and reversing Xist-induced chromatin inaccessibility. We identify
      the RNA-binding protein hnRNPK as the principal XR-PID binding factor required to
      recruit PCGF3/5-PRC1. Accordingly, synthetically tethering hnRNPK to Xist RNA
      lacking XR-PID is sufficient for Xist-dependent Polycomb recruitment. Our
      findings define a key pathway for Polycomb recruitment by Xist RNA, providing
      important insights into mechanisms of chromatin modification by non-coding RNA.

PMID- 29220665
TI  - mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell
      Maintenance.
AB  - The balance between self-renewal and differentiation ensures long-term
      maintenance of stem cell (SC) pools in regenerating epithelial tissues. This
      balance is challenged during periods of high regenerative pressure and is often
      compromised in aged animals. Here, we show that target of rapamycin (TOR)
      signaling is a key regulator of SC loss during repeated regenerative episodes. In
      response to regenerative stimuli, SCs in the intestinal epithelium of the fly and
      in the tracheal epithelium of mice exhibit transient activation of TOR signaling.
      Although this activation is required for SCs to rapidly proliferate in response
      to damage, repeated rounds of damage lead to SC loss. Consistently, age-related
      SC loss in the mouse trachea and in muscle can be prevented by pharmacologic or
      genetic inhibition, respectively, of mammalian target of rapamycin complex 1
      (mTORC1) signaling. These findings highlight an evolutionarily conserved role of
      TOR signaling in SC function and identify repeated rounds of mTORC1 activation as
      a driver of age-related SC decline.

PMID- 29220671
TI  - Structural comparison among the 2013-2017 avian influenza A H5N6 hemagglutinin
      proteins: A computational study with epidemiological implications.
AB  - Avian influenza viruses easily spread allowing viral re-assortment to simply
      occur which in-turn increases the potential for a pandemic. A novel 2013 H5N6
      influenza strain was detected among the avian population and was reported to
      continuously evolve, however, this was never structurally demonstrated. Here, we
      elucidated the putative structural evolution of the novel H5N6 influenza strain.
      Throughout this study, we analyzed 2013-2017 H5N6 HA protein models. Model
      quality was first verified before further analyses and structural comparison was
      made using superimposition. We found that Leu was inserted at position 1291 among
      the 2013-2015 models while Leu was not inserted among the 2016-2017 models.
      Moreover, presence of Leu at position 1291 shifts residue E1261 by 159.6 degrees 
      affecting nearby residues which may explain the difference between the 2013-2015
      and 2016-2017 HA structural groups. Similarly, we believe that our results would
      support the hypothesis that the current H5N6 strain is still continuously
      evolving.

PMID- 29220673
TI  - De Novo Variants in GRIA4 Lead to Intellectual Disability with or without
      Seizures and Gait Abnormalities.
AB  - Using trio whole-exome sequencing, we have identified de novo heterozygous
      pathogenic variants in GRIA4 in five unrelated individuals with intellectual
      disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as
      GluR4, which is found on excitatory glutamatergic synapses and is important for
      learning and memory. Four of the variants are located in the highly conserved
      SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra
      cellular domain. Molecular modeling of the altered protein showed that three of
      the variants in the SYTANLAAF motif orient toward the center of the pore region
      and most likely lead to disturbance of the gating mechanism. The fourth variant
      in the SYTANLAAF motif most likely results in reduced permeability. The variant
      in the extracellular domain potentially interferes with the binding between the
      monomers. On the basis of clinical information and genetic results, and the fact
      that other subunits of the AMPA receptor have already been associated with
      neurodevelopmental disorders, we suggest that pathogenic de novo variants in
      GRIA4 lead to intellectual disability with or without seizures, gait
      abnormalities, problems of social behavior, and other variable features.

PMID- 29220675
TI  - Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney
      Malformations.

PMID- 29220678
TI  - Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger
      Spectrum Disorder.
AB  - Zellweger spectrum disorders (ZSDs) are autosomal-recessive disorders that are
      caused by defects in peroxisome biogenesis due to bi-allelic mutations in any of
      13 different PEX genes. Here, we identified seven unrelated individuals affected
      with an apparent dominant ZSD in whom a heterozygous mutant PEX6 allele
      (c.2578C>T [p.Arg860Trp]) was overrepresented due to allelic expression imbalance
      (AEI). We demonstrated that AEI of PEX6 is a common phenomenon and is correlated
      with heterozygosity for a frequent variant in the 3' untranslated region (UTR) of
      the mutant allele, which disrupts the most distal of two polyadenylation sites.
      Asymptomatic parents, who were heterozygous for PEX c.2578C>T, did not show AEI
      and were homozygous for the 3' UTR variant. Overexpression models confirmed that
      the overrepresentation of the pathogenic PEX6 c.2578T variant compared to wild
      type PEX6 c.2578C results in a peroxisome biogenesis defect and thus constitutes
      the cause of disease in the affected individuals. AEI promoting the
      overrepresentation of a mutant allele might also play a role in other autosomal
      recessive disorders, in which only one heterozygous pathogenic variant is
      identified.

PMID- 29220679
TI  - Interaction between pre-treatment drug use and heterogeneity of psychiatric
      diagnosis predicts outcomes in outpatients with co-occurring disorders.
AB  - We examined whether the interaction of baseline stimulant use, assessed by urine
      drug tests, and type of serious mental illness (SMI) diagnosis predicted
      stimulant use in a trial of contingency management (CM). The interaction between
      baseline stimulant use and SMI diagnoses was significant in the overall sample
      (p=0.002) when controlling for the main effects of treatment condition, baseline
      stimulant use, and SMI diagnosis. Similar results were also found within the CM
      sample. Individuals with bipolar disorder were more or less likely, depending on
      their baseline stimulant-drug test results, to use stimulants during treatment
      compared to those with other SMI diagnoses.

PMID- 29220681
TI  - Experience of caregiving and coping strategies in caregivers of adolescents with
      an eating disorder: A comparative study.
AB  - Caring for a relative with an eating disorder (ED) is associated with heightened
      psychological distress, which, according to a stress-coping model, may be
      influenced by coping and appraisal. However, limited quantitative studies have
      assessed coping in ED caregivers. This cross-sectional study aims to assess 1)
      the differences in coping between caregivers of three groups: patients with an
      ED, patients with a substance use disorder, and healthy teens, and 2) the patient
      and caregiver variables associated with coping and appraisal of the caregiving
      experience. A one-way MANOVA was significant for caregiver group for mothers, but
      not fathers. Mothers of both patient groups used more self-sufficient problem
      focused coping than mothers of healthy teens. Patient caregivers did not
      significantly differ from caregivers of healthy teens in their use of avoidance.
      Mothers used social support strategies more than fathers. A positive experience
      of caregiving was significantly associated with the use of approach-oriented
      coping in ED caregivers and a negative experience of caregiving was significantly
      associated with avoidance in ED mothers. Older ED caregivers were less likely to
      use avoidance. Future interventions could help ED caregivers to recognize their
      coping preferences and how to appropriately use these strategies when faced with
      illness-related stressors.

PMID- 29220682
TI  - Searching online to buy commonly prescribed psychiatric drugs.
AB  - The use of online pharmacies to purchase prescription drugs is increasing. The
      patient experience when searching to buy commonly prescribed psychiatric drugs
      was investigated. Using the search term "buy [drug name] online" in Google, 38
      frequently prescribed drugs, including 13 with a high potential for abuse, were
      searched by brand and generic names. The first page of results were analyzed,
      including with pharmacy certification checkers and ICANN WHOIS. Search results
      for all drugs yielded 167 pharmacies, of which 147 (88%) did not require a
      prescription. Considering all searches, the average number of pharmacies
      requiring a prescription was 2.7 for a brand name drug and 2.4 for a generic
      name. A phrase like "buy without a prescription" usually appeared on the search
      results page. All results for drugs with a high potential for abuse were for
      illegal pharmacies. Information from certification agencies was often
      conflicting. Most pharmacies were registered internationally. Patients searching
      online to purchase prescription psychiatric drugs are presented predominantly
      with illegal pharmacies, and find conflicting certification data. Patient
      education should address typical search results. Societal pressures may increase
      the use of online pharmacies including prescription drug costs, stigma, loss of
      trust in expert opinion, and the changing patient role.

PMID- 29220677
TI  - A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via
      GWAS Summary Statistics.
AB  - Despite the success of large-scale genome-wide association studies (GWASs) on
      complex traits, our understanding of their genetic architecture is far from
      complete. Jointly modeling multiple traits' genetic profiles has provided
      insights into the shared genetic basis of many complex traits. However, large
      scale inference sets a high bar for both statistical power and biological
      interpretability. Here we introduce a principled framework to estimate annotation
      stratified genetic covariance between traits using GWAS summary statistics.
      Through theoretical and numerical analyses, we demonstrate that our method
      provides accurate covariance estimates, thereby enabling researchers to dissect
      both the shared and distinct genetic architecture across traits to better
      understand their etiologies. Among 50 complex traits with publicly accessible
      GWAS summary statistics (Ntotal~ 4.5 million), we identified more than 170 pairs
      with statistically significant genetic covariance. In particular, we found strong
      genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic
      lateral sclerosis (ALS), two major neurodegenerative diseases, in single
      nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs
      located in the predicted functional genome. Joint analysis of LOAD, ALS, and
      other traits highlights LOAD's correlation with cognitive traits and hints at an
      autoimmune component for ALS.

PMID- 29220674
TI  - ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder.
AB  - ACTB encodes beta-actin, an abundant cytoskeletal housekeeping protein. In
      humans, postulated gain-of-function missense mutations cause Baraitser-Winter
      syndrome (BRWS), characterized by intellectual disability, cortical
      malformations, coloboma, sensorineural deafness, and typical facial features. To
      date, the consequences of loss-of-function ACTB mutations have not been proven
      conclusively. We describe heterozygous ACTB deletions and nonsense and frameshift
      mutations in 33 individuals with developmental delay, apparent intellectual
      disability, increased frequency of internal organ malformations (including those
      of the heart and the renal tract), growth retardation, and a recognizable facial
      gestalt (interrupted wavy eyebrows, dense eyelashes, wide nose, wide mouth, and a
      prominent chin) that is distinct from characteristics of individuals with BRWS.
      Strikingly, this spectrum overlaps with that of several chromatin-remodeling
      developmental disorders. In wild-type mouse embryos, beta-actin expression was
      prominent in the kidney, heart, and brain. ACTB mRNA expression levels in
      lymphoblastic lines and fibroblasts derived from affected individuals were
      decreased in comparison to those in control cells. Fibroblasts derived from an
      affected individual and ACTB siRNA knockdown in wild-type fibroblasts showed
      altered cell shape and migration, consistent with known roles of cytoplasmic beta
      actin. We also demonstrate that ACTB haploinsufficiency leads to reduced cell
      proliferation, altered expression of cell-cycle genes, and decreased amounts of
      nuclear, but not cytoplasmic, beta-actin. In conclusion, we show that
      heterozygous loss-of-function ACTB mutations cause a distinct pleiotropic
      malformation syndrome with intellectual disability. Our biological studies
      suggest that a critically reduced amount of this protein alters cell shape,
      migration, proliferation, and gene expression to the detriment of brain, heart,
      and kidney development.

PMID- 29220680
TI  - Adherence to physical activity recommendations and physical and mental health
      risk in people with severe mental illness in Uganda.
AB  - This study investigated cardio-metabolic risk factors among patients with severe
      mental illness who do or do not meet the recommendations of 150min per week of
      physical activity. A secondary aim was to assess whether those that do meet the
      recommendations report lower levels of mental health symptoms. 107 (60?) Ugandan
      in- and outpatients (mean age=34.4 +/- 9.7 years) with severe mental illness
      (depression=7, bipolar disorder=55, schizophrenia=45) completed the Physical
      Activity Vital Sign (PAVS) method and Brief Symptoms Inventory -18. Participants
      were also screened for abdominal obesity (waist circumference>90cm), overweight
      (body mass index>=25) and hypertension (systolic pressure>=140mmHg and/or
      diastolic pressure>=90mmHg).48.6% (n = 52) of patients met the physical activity
      recommendations as assessed by the PAVS method. 41.1% (n = 44) were overweight,
      40.2% (n = 43) had abdominal obesity and 23.4% (n = 25) had hypertension. Those
      who did not meet the physical activity recommendations were significantly older,
      had a higher BSI-18 somatisation score, and had a higher risk of overweight
      [relative risk (RR) = 2.88, 95% confidence interval (CI) = 1.59-4.99], abdominal
      obesity (RR = 1.82, 95%CI = 1.13-2.93), and hypertension (RR = 2.16, 95%CI = 0.99
      4.73). The PAVS is a feasible method of assessing physical activity among
      patients with severe mental illness in a low resource setting. The PAVS may have
      clinical utility for physical and mental health risk stratification.

PMID- 29220683
TI  - Psychological pathway to suicidal ideation among people living with HIV/AIDS in
      China: A structural equation model.
AB  - People living with HIV/AIDS (PLWHA) have higher rates of suicide than does the
      general population. It is critical to interpret the intricate relationships among
      various psychological variables that increase the risk of suicidal ideation among
      PLWHA in China. An institutional based cross-sectional study was conducted from
      Jul to Aug 2016 in Nanjing, China, using a self-reporting questionnaire. A total
      of 465 PLWHA participated. Sociodemographic, psychological variables and suicide
      information about the participants were collected. Structural equation modeling
      (SEM)-path analysis was used to analyze the cross-sectional data. The final
      structural equation model had a highly satisfactory fit. Among PLWHA, perceived
      stigma had the greatest accumulated total effect on suicidal ideation, with both
      a direct effect and indirect effect through self-esteem and depression.
      Additionally, self-esteem had the second greatest total effect on suicidal
      ideation and was influenced by social support. Depression contributed directly to
      suicidal ideation and partly mediated the association of perceived stigma and
      self-esteem with suicidal ideation. These findings suggest that self-esteem and
      depression, particularly perceived stigma, play important roles in suicidal
      ideation among PLWHA. Enhancing personal self-esteem or social support might also
      reduce perceived stigma and may be an important target for intervention to
      decrease suicidal ideation among PLWHA.

PMID- 29220684
TI  - Predictors of remission from PTSD symptoms after sexual and non-sexual trauma in
      the community: A mediated survival-analytic approach.
AB  - Epidemiological data on the chronicity of posttraumatic stress disorder (PTSD)
      symptoms in relation to trauma type and underlying pathways are rare. The current
      study explored how PTSD symptoms change over time across different trauma types
      and examined mediators of their persistence. A trauma-exposed community sample,
      whereof approximately one quarter met diagnostic criteria for PTSD, provided
      retrospective data on the duration of PTSD symptoms. Those who remitted and those
      who had not at the time of assessment were compared regarding worst trauma,
      symptom severity, comorbidity, demographic and treatment-seeking variables. Time
      to remission was estimated using Cox proportional hazard models including
      candidate predictors of remission. A mediated survival analysis was used to
      explore indirect pathways that explain trauma-specific differences in remission
      times. Both the full sample and PTSD subgroup were analyzed separately. Overall,
      lower socio-economic status, lifetime and childhood sexual trauma, symptom
      severity, comorbid depression and past treatment were associated with non- and
      longer remissions. PTSD avoidance symptoms and comorbid depression were found to
      mediate longer remission times after lifetime or childhood sexual trauma. Our
      findings provide insight into the mechanisms and complicating factors of
      remission from PTSD symptoms after trauma, which might have important
      implications for therapeutic interventions.

PMID- 29220685
TI  - Parental psychopathology, adult attachment and risk of 12-month suicidal
      behaviours.
AB  - BACKGROUND: The mechanisms by which parental psychopathology and vulnerability to
      suicide is transmitted to offspring is not well understood. parental
      psychopathology and behaviour may impact upon the normal emotional and
      psychological adjustment of their offspring in various ways. Research shows
      attachment insecurities may also be a key factor in the facilitation of suicidal
      behaviours. OBJECTIVE: To examine adult attachment insecurities as a potential
      mediating pathway between parental psychopathology and 12-month suicidality.
      METHOD: The study utilized data from the National co-morbidity Survey-Replication
      (NCS-R, N = 5692). Parental psychopathology was assessed using items from the
      Familial History of Psychiatric Disorders section of the NSC-R in conjunction
      with items designed to capture dimensions of attachment and suicidal behaviours.
      RESULTS: Resultant analyses demonstrated specificity effects in that, parental
      psychopathology was associated with specific suicidal components through specific
      dimensions of attachment. DISCUSSION: The results align with literature linking
      parental psychopathology to both attachment insecurities and risk of suicide.
      Crucially, this study bridges these research areas by presenting attachment
      insecurity as possible risk indicator and intervening factor between parental
      mental health and behaviour and specific indicators of suicide.

PMID- 29220676
TI  - Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index
      Distribution.
AB  - A growing number of single-nucleotide polymorphisms (SNPs) have been associated
      with body mass index (BMI) and obesity, but whether the effects of these obesity
      susceptibility loci are uniform across the BMI distribution remains unclear. We
      studied the effects of 37 BMI-associated SNPs in 75,230 adults of European
      ancestry across BMI percentiles by using conditional quantile regression (CQR)
      and meta-regression (MR) models. The effects of nine SNPs (24%)-rs1421085 (FTO; p
      = 8.69 * 10-15), rs6235 (PCSK1; p = 7.11 * 10-6), rs7903146 (TCF7L2; p = 9.60 *
      10-6), rs11873305 (MC4R; p = 5.08 * 10-5), rs12617233 (FANCL; p = 5.30 * 10-5),
      rs11672660 (GIPR; p = 1.64 * 10-4), rs997295 (MAP2K5; p = 3.25 * 10-4), rs6499653
      (FTO; p = 6.23 * 10-4), and rs3824755 (NT5C2; p = 7.90 * 10-4)-increased
      significantly across the sample BMI distribution. We showed that such increases
      stemmed from unadjusted gene interactions that enhanced the effects of SNPs in
      persons with a high BMI. When 125 height-associated SNPs were analyzed for
      comparison, only one (<1%), rs6219 (IGF1, p = 1.80 * 10-4), showed effects that
      varied significantly across height percentiles. Cumulative gene scores of these
      SNPs (GS-BMI and GS-height) showed that only GS-BMI had effects that increased
      significantly across the sample distribution (BMI: p = 7.03 * 10-37; height: p =
      0.499). Overall, these findings underscore the importance of gene-gene and gene
      environment interactions in shaping the genetic architecture of BMI and advance a
      method for detecting such interactions by using only the sample outcome
      distribution.

PMID- 29220689
TI  - Preparation of magnetically recoverable bentonite-Fe3O4-MnO2 composite particles
      for Cd(II) removal from aqueous solutions.
AB  - In this study, bentonite-Fe3O4-MnO2 composite was synthesized by combining
      bentonite with Fe3O4 and MnO2 through co-precipitation. Vibrating-sample
      magnetometry, scanning electron microscopy with energy-dispersive X-ray
      spectrometry, transmission electron microscopy, Brunauer-Emmett-Teller
      measurements, and X-ray powder diffraction techniques were used to characterize
      the composite. The composite consists of Fe3O4 nanoparticles orderly assembled on
      the surface of bentonite and an outer layer of MnO2 sheets. The composite's
      particles possess a saturation magnetization of 13.4-30.5 emu/g and a high
      specific surface area (203.89 m2/g). The adsorption behaviors of the composite in
      Cd(II) removal were evaluated by batch equilibrium experiments. Kinetic and
      isothermal data fit well the pseudo-second-order and the Freundlich models,
      respectively. Adsorption reached equilibrium within 30 min, and the Freundlich
      capacity of the composite was 35.35 mg/g. The adsorption capacity of Cd(II)
      increased with increasing pH and was dependent on the ionic strength. Fourier
      transform infrared spectroscopy and X-ray photoelectron spectroscopy showed the
      combination of surface hydroxyl groups of the composite and Cd(II) in the
      solution. The prepared composite can be easily recycled and reused by taking
      advantage of its magnetic properties. The results show that the designed
      composite is a promising absorbent for the treatment of Cd-contaminated water.

PMID- 29220690
TI  - On the selectivity, specificity and signalling potential of the long-distance
      movement of messenger RNA.
AB  - Messenger RNA (mRNA) can move through the vascular system in plants. Until
      recently the transport of mRNA had been demonstrated only for a few well
      documented cases, leading to the suggestion that transport was selective and
      specific. The extent of this long-distance transport has now been shown to be on
      the genomic scale with thousands of transcripts covering broad regions of gene
      ontological space. In light of this recent data, I revisit proposed mechanisms of
      transport of mRNA and critically assess their potential role in signalling.

PMID- 29220686
TI  - Broadening the photoresponsive activity of anatase titanium dioxide particles via
      decoration with partial gold shells.
AB  - Titanium dioxide (TiO2) has gained increasing interest in materials research due
      to its outstanding properties and promising applications in a wide range of
      fields. From this perspective, we report the synthesis of custom-designed anatase
      TiO2 submicrometer particles coated with partial Au shells (ATiO2-AuShl). The
      synthetic strategy used herein yields uniformly shaped monodisperse particles.
      Amorphous TiO2 core particles were synthesized using template-free oxidation and
      hydrolysis of titanium nitride (TiN); subsequent hydrothermal treatment generated
      anatase TiO2 (ATiO2) particles. Coating ATiO2 particles with partial Au shells
      was accomplished using a simple seeded-growth method. Evaluation of the optical
      properties of these ATiO2-AuShl particles showed that these submicrometer
      composites exhibited an intense absorption peak for TiO2 in the UV region (~326
      nm) and a broad extinction band in the visible range (~650 nm) arising from the
      incomplete Au shell. These ATiO2-AuShl composite particles provide a unique and
      effective means for broadening the optical response of TiO2-based nano- and
      micron-scale materials. The simplicity of our synthetic method should broaden the
      application of ATiO2-AuShl particles in various visible light-driven
      technologies.

PMID- 29220688
TI  - Effects of surface modification and size on oral drug delivery of mesoporous
      silica formulation.
AB  - The surface chemistry and size of nanoparticles can greatly impact their
      interaction with biological pathways and alter efficacy. However, the interplay
      between surface modification and particle size has not been well investigated
      especially for oral delivery. It is necessary to maximize the bioavailability of
      loading therapeutics. Here, we prepared different sized mesoporous silica
      nanoparticles (100-500 nm) and conjugated them with polyethylenimine-coated
      carbondots (PCD) for effective transepithelial absorption. The nanoparticles were
      also coated with polyethylene glycol (PEG) polymers for improved mucus
      permeability. These mesoporous silica nanoparticles conjugated to PCD and coated
      in PEG (MSN@PCD@PEG) were used to study the influence of particle size and
      surface chemistry on transepithelial transport and bioavailability. Results
      demonstrated that the MSN@PCD@PEG with a diameter 250 nm had the highest
      transepithelial transport and oral bioavailability compared to other
      formulations. Drug release, endocytosis pathways, transepithelial transport and
      degradation of these different nanocarriers were systematically studied in order
      to investigate effects of size variety. The findings indicated that nanoparticle
      based oral drug delivery can be potentially improved by adjusting physicochemical
      properties. We believe that understanding the importance of surface chemistry and
      particle size in the oral delivery will improve nanoparticle engineering and oral
      application.

PMID- 29220691
TI  - Bioaccumulation of oil compounds in the high-Arctic copepod Calanus hyperboreus.
AB  - Oil and gas exploration in the Arctic will increase the risk for accidental oil
      spills and thereby have a potential impact on the ecosystem and the organisms
      inhabiting these areas. Lipid rich copepods are an important food source for
      higher trophic levels in Arctic marine ecosystems. However, high lipid content
      and a slower metabolism increase the risk for bioaccumulation in Arctic species.
      Here we exposed three late development stages of the lipid rich high-Arctic
      copepod species Calanus hyperboreus to two different 14C-marked crude oil model
      compounds, the alkane dodecane (log Kow 6.10) and the polycyclic aromatic
      hydrocarbon (PAH) phenanthrene (log Kow 4.46) on a short-term scale of 4days.
      Exposure was followed by a depuration phase of 3days. We observed a difference in
      estimated bioaccumulation of the two model compounds between stages and found a
      slower depuration of dodecane than of phenanthrene in the two largest and most
      lipid rich stages. However, depuration of dodecane and phenanthrene was non
      significant for all three stages. The results indicate that even short-term
      exposure may result in long-term bioaccumulation and internal exposure of oil
      compounds in the lipid rich high-Arctic copepods C. hyperboreus. Slow elimination
      and depuration of oil components indicate a risk for transfer of oil component up
      the food web to pelagic fish, seabirds and baleen whales.

PMID- 29220687
TI  - Development of a novel functional core-shell-shell nanoparticles: From design to
      anti-bacterial applications.
AB  - This article reports the synthesis and functionalization of a novel CuO@SiO2
      APTES@Ag0 core-shell-shell material using a simple and low-cost process. The
      growth, design strategies and synthesis approach are the key factors for the
      development of CuO@SiO2-APTES@Ag0 as efficient material with enhanced
      antibacterial activity. We investigated the morphology, surface charge, structure
      and stability of our new core-shell-shell by atomic force microscopy, scanning
      electron microscopy, energy dispersive X-ray, Fourier transform infrared and UV
      visible spectroscopies, zeta potential measurements, and differential scanning
      calorimetry. The covalent surface grafting of APTES (3
      (aminopropyl)triethoxysilane) onto CuO@SiO2 involving electrostatic interactions
      was confirmed. Size measurements and Scanning electron images showed that both
      APTES grafting and SiO2/Ag shells dropped on the surface of CuO produced
      structural compaction. UV-Vis spectroscopy proved to be a fast and convenient way
      to optically detect SiO2 shell on the surface of colloids. Additionally, the Ag
      decorated CuO@SiO2-APTES surfaces were found to possess antibacterial activity
      and thermally more stable than undecorated surfaces. CuO@SiO2-APTES@Ag0 core
      shell had antibacterial properties against Gram-positive bacteria making it a
      promising candidate for antibacterial applications.

PMID- 29220692
TI  - PLAG alleviates chemotherapy-induced thrombocytopenia via promotion of
      megakaryocyte/erythrocyte progenitor differentiation in mice.
AB  - Previously, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated
      diglyceride) was reported to have an effect on the proliferation of hematopoietic
      stem cells (HSCs) or to contribute to the prevention of chemotherapy-induced
      neutropenia. In this study, we examined the role of PLAG in the differentiation
      of bone marrow cells from HSCs into progenitor cells in mice. After 15days, the
      lineage-negative cells, especially megakaryocyte/erythrocyte progenitors (MEP),
      were significantly increased in mice that received daily PLAG administration
      compared to those in the untreated mice. Furthermore, we explored the possibility
      that the PLAG-induced increase in MEP will contribute to reduction of
      chemotherapy-induced thrombocytopenia (CIT) in a thrombocytopenia mouse model.
      Mice were administrated 5-fluorouracil (5-FU) and PLAG. After 7days, bone marrow
      cells were analyzed. Treatment with 5-FU powerfully decreased myeloid precursor
      populations and treatment with 5-FU/PLAG resulted in reduction of decreased
      myeloid progenitor cell numbers. In addition, numbers of circulating platelets
      were also increased by PLAG treatment. Taken together, PLAG plays a role in
      differentiating HSCs toward MEP and alleviating chemotherapy-induced bone marrow
      cell reduction. Thus PLAG shows its potential to augment the therapeutic effect
      of anti-cancer drugs-induced thrombocytopenia.

PMID- 29220694
TI  - Impulsive responding in threat and reward contexts as a function of PTSD symptoms
      and trait disinhibition.
AB  - We examined current posttraumatic stress disorder (PTSD) symptoms, trait
      disinhibition, and affective context as contributors to impulsive and self
      destructive behavior in 94 trauma-exposed Veterans. Participants completed an
      affective Go/No-Go task (GNG) with different emotional contexts (threat, reward,
      and a multidimensional threat/reward condition) and current PTSD, trait
      disinhibition, and risky/self-destructive behavior measures. PTSD interacted with
      trait disinhibition to explain recent engagement in risky/self-destructive
      behavior, with Veterans scoring high on trait disinhibition and current PTSD
      symptoms reporting the highest levels of these behaviors. On the GNG task,
      commission errors were also associated with the interaction of PTSD symptoms and
      trait disinhibition. Specifically, PTSD symptoms were associated with greater
      commission errors in threat vs. reward contexts for individuals who were low on
      trait disinhibition. In contrast, veterans high on PTSD and trait disinhibition
      exhibited the greatest number of commission errors in the multidimensional
      affective context that involved both threat and reward processing. Results
      highlight the interactive effects of PTSD and disinhibited personality traits, as
      well as threat and reward systems, as risk factors for impulsive and self
      destructive behavior in trauma-exposed groups. Findings have clinical
      implications for understanding heterogeneity in the expression of PTSD and its
      association with disinhibited behavior.

PMID- 29220693
TI  - Type 1 von Willebrand disease due to a vicinal cysteine loss (p.C524Y) disclosed
      after a thrombotic episode.

PMID- 29220695
TI  - Altered resting state functional connectivity in early course schizophrenia.
AB  - Impaired connectivity is proposed to underlie pathophysiology of schizophrenia.
      Existing studies on functional connectivity show inconsistent results. We
      examined functional connectivity in a clinically homogenous sample of 34 early
      course schizophrenia patients compared with/to 19 healthy controls using resting
      state functional magnetic resonance imaging (rsfMRI). Mean duration of illness
      for schizophrenia patients was 4 +/- 1.78 years. Following a comprehensive
      clinical assessment, rsfMRI data were acquired using a 3.0 T magnetic resonance
      imaging scanner, and analyzed using FSL version 5.01 software (FMRIB's Software
      Library, www.fmrib.ox.ac.uk/fsl). Compared to healthy controls, schizophrenia
      patients had significantly decreased functional connectivity in the left fronto
      parietal network, lateral and medial visual network, motor network, default mode
      network and auditory network. Our data suggests significant functional
      hypoconnectivity in selected brain networks in early schizophrenia patients
      compared to controls. It is likely that the observed functional hypoconnectivity
      may be associated with features of schizophrenia other than those examined in
      this study. It is possible that hypoconnectivity is necessary but not sufficient
      to the clinical manifestation of schizophrenia. The examination of functional
      connectivity as a biomarker should be extended to a wider array of disease
      phenotypes to better understand its significance.

PMID- 29220701
TI  - Molecular criteria for mutagenesis by DNA methylation: Some computational
      elucidations.
AB  - Alkylating agents and N-nitroso compounds are well-known mutagens and carcinogens
      which act by alkylating DNA at the nucleobase moieties. Criteria for mutagenicity
      through DNA alkylation include (a) absence of the Watson-Crick (N1-guanine and N3
      thymine) protons, (b) rotation of the alkyl group away from the H-bonding zone,
      (c) configuration of the alkylated base pair close to the Watson-Crick type. This
      computational study brings together these three molecular criteria for the first
      time. Three methylated DNA bases-N7-methylguanine, O6-methylguanine and O4
      methylthymine-are studied using computational chemical methods. Watson-Crick
      proton loss is predicted more feasible for the mutagenic O6-methylguanine and O4
      methylthymine than for the non-mutagenic N7-methylguanine in agreement with the
      observed trend for pKa values. Attainment of a conformer conducive to mutagenesis
      is more feasible for O6-methylguanine than for O4-methylthymine, though the
      latter is more mutagenic. These methylated bases yield 9 H-bonded pairs with
      normal DNA bases. At biological pH, O6-methylguanine and O4-methylthymine would
      yield stable mutagenic pairs having Watson-Crick type configuration by H-bonded
      pairing with thymine and guanine respectively, while N7-methylguanine would yield
      a non-mutagenic pair with cytosine. The three criteria thus well differentiate
      the non-mutagenic N7-methylguanine from the mutagenic O6-methylguanine and O4
      methylthymine in good accord with experimental observations.

PMID- 29220696
TI  - Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS
      generation via regulating the SIRT1/eNOS/NF-kappaB pathway in vivo and in vitro.
AB  - Caffeic acid phenethyl ester (CAPE) could ameliorate myocardial
      ischemia/reperfusion injury (MIRI) by various mechanisms, but there hadn't been
      any reports on that CAPE could regulate silent information regulator 1 (SIRT1)
      and endothelial nitric oxide synthase (eNOS) to exert cardioprotective effect.
      The present study aimed to investigate the cardioprotective potential of caffeic
      acid o-nitro phenethyl ester (CAPE-oNO2) on MIRI and the possible mechanism based
      on the positive control of CAPE. The SD rats were subjected to left coronary
      artery ischemia /reperfusion (IR) and the H9c2 cell cultured in
      hypoxia/reoxygenation (HR) to induce the MIRI model. Prior to the procedure,
      vehicle, CAPE or CAPE-oNO2 were treated in the absence or presence of a SIRT1
      inhibitor nicotinamide (NAM) and an eNOS inhibitor Nomega-nitro-L-arginine methyl
      ester (L-NAME). In vivo, CAPE and CAPE-oNO2 conferred a cardioprotective effect
      as shown by reduced myocardial infarct size, cardiac marker enzymes and
      structural abnormalities. From immunohistochemical and sirius red staining, above
      two compounds ameliorated the TNF-alpha release and collagen deposition of IR rat
      hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO
      release and suppress NF-kappaB signaling, to reduce the malondialdehyde content
      and cell necrosis. In vitro, they could inhibit HR-induced H9c2 cell apoptosis
      and ROS generation by activating SIRT1/eNOS pathway and inhabiting NF-kappaB
      expression. Emphatically, CAPE-oNO2 presented the stronger cardioprotection than
      CAPE both in vivo and in vitro. However, NAM and L-NAME eliminated the CAPE-oNO2
      mediated cardioprotection by restraining SIRT1 and eNOS expression, respectively.
      It suggested that CAPE-oNO2 ameliorated MIRI by suppressing the oxidative stress,
      inflammatory response, fibrosis and necrocytosis via the SIRT1/eNOS/NF-kappaB
      pathway.

PMID- 29220702
TI  - The effect of subjective awareness measures on performance in artificial grammar
      learning task.
AB  - Systematic research into implicit learning requires well-developed awareness
      measurement techniques. Recently, trial-by-trial measures have been widely used.
      However, they can increase complexity of a study because they are an additional
      experimental variable. We tested the effects of these measures on performance in
      artificial grammar learning study. Four groups of participants were assigned to
      different awareness measures conditions: confidence ratings, post-decision
      wagering, decision strategy attribution or none. Decision-strategy-attribution
      participants demonstrated better grammar learning and longer response times
      compared to controls. They also exhibited a conservative bias. Grammaticality by
      itself was a stronger predictor of strings endorsement in decision-strategy
      attribution group compared to other groups. Confidence ratings and post-decision
      wagering only affected the response times. These results were supported by an
      additional experiment that used a balanced chunk strength design. We conclude
      that a decision-strategy-attribution procedure may force participants to adopt an
      analytical decision-making strategy and rely mostly on conscious knowledge of
      artificial grammar.

PMID- 29220700
TI  - Prognostic importance of Aurora Kinases and mitotic spindle genes transcript
      levels in Myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease
      characterized by insufficiency of bone marrow, increase of apoptosis and
      increased risk of acute leukemia progression. Proteins related to the mitotic
      spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the
      regulation of the cell cycle (p21) are directly related to chromosomal stability
      and tumor development. This study aimed to evaluate the mRNA expression levels of
      these genes in 101 MDS patients using a real-time PCR methodology. We identified
      that CDC20 expression are increased in patients with dysmegakaryopoiesis
      (p=0.024), thrombocytopenia (p=0.000) and high-risk patients (p=0.014, 0.018)
      MAD2 expression are decreased in patients with 2 or 3 cytopenias (p=0.000) and
      neutrophil below 800/mm3. TPX2 is also overexpressed in patients presenting
      dysmegakaryopoiesis (p=0.009). A decrease in AURKA and AURKB expression were
      observed in patients with altered karyotype (p=0.000), who presented dysplasia in
      3 lineages (p=0.000; 0.017) and hemoglobin inferior to 8g/dL (p=0.024). The
      expression of AURKA, AURKB and MAD2 (p=0.000; 0.001; 0.025) were decreased in
      patients with hypoplastic MDS, associated with high frequency of chromosomal
      alterations and high mortality rate. This study reaffirms the importance of
      aurora kinases and mitotic spindle genes to the pathogenesis and clinical
      evolution of MDS.

PMID- 29220704
TI  - How do peers influence BMI? Evidence from randomly assigned classrooms in South
      Korea.
AB  - Obesity among children is an important public health concern, and social networks
      may play a role in students' habits that increase the likelihood of being
      overweight. We examine data from South Korean middle schools, where students are
      randomly assigned to classrooms, and exploit the variation in peer body mass
      index. We use the number of peers' siblings as an instrument to account for
      endogeneity concerns and measurement error. Heavier peers increase the likelihood
      that a student is heavier; there is no spurious correlation for height, which is
      unlikely to have peer contagion. Public policy that targets obesity can have
      spillovers through social networks.

PMID- 29220703
TI  - Referral to specialist physiotherapists in the management of whiplash associated
      disorders: Perspectives of healthcare practitioners.
AB  - BACKGROUND: Guidelines for whiplash associated disorders (WAD) recommend early
      referral to specialists (e.g. specialist physiotherapists) of people who are not
      recovering. This recommendation is a key component of a proposed clinical pathway
      of care for WAD. OBJECTIVE: To explore healthcare practitioners' opinions about
      referral to specialist physiotherapists of people with WAD at high risk of non
      recovery. DESIGN: Qualitative descriptive study. METHODS: Six focus groups were
      conducted among primary care allied-health practitioners (n = 16) and specialist
      physiotherapists (n = 12) in New South Wales and Queensland, Australia.
      Discussions were audio recorded and transcribed for thematic analysis. RESULTS:
      Ten themes were generated from analysis. Practitioners appeared to have good
      knowledge of indicators for referral; however, referrals were often made to the
      medical practitioner, less commonly to specialist physiotherapists. There was
      general support for referral to specialist physiotherapists, which was deemed as
      a viable alternative for people who are not recovering. Practitioners, however,
      had differing views about the attributes of a specialist physiotherapist and
      referral timeframe. A number of factors have been identified to influence the
      referral process and practitioners expressed specific expectations of the desired
      outcomes of referral as well as considerations for specialist management
      approaches. There was strong support for a collaborative approach in management
      that involved the referring practitioner. CONCLUSION: Results support the
      feasibility of referral to specialist physiotherapists despite limited uptake in
      practice and recognised barriers to referral. These findings have implications
      for further study and adopting strategies to facilitate effective implementation
      and translation of the proposed pathway into primary care practice.

PMID- 29220697
TI  - Metabolism of hydrogen sulfide (H2S) and Production of Reactive Sulfur Species
      (RSS) by superoxide dismutase.
AB  - Reactive sulfur species (RSS) such as H2S, HS*, H2Sn, (n = 2-7) and HS2*- are
      chemically similar to H2O and the reactive oxygen species (ROS) HO*, H2O2, O2*-
      and act on common biological effectors. RSS were present in evolution long before
      ROS, and because both are metabolized by catalase it has been suggested that
      "antioxidant" enzymes originally evolved to regulate RSS and may continue to do
      so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD)
      using amperometric electrodes for dissolved H2S, a polysulfide-specific
      fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides
      (H2S2-H2S5). H2S was concentration- and oxygen-dependently oxidized by 1MUM SOD
      to polysulfides (mainly H2S2, and to a lesser extent H2S3 and H2S5) with an EC50
      of approximately 380MUM H2S. H2S concentrations > 750MUM inhibited SOD oxidation
      (IC50 = 1.25mM) with complete inhibition when H2S > 1.75mM. Polysulfides were not
      metabolized by SOD. SOD oxidation preferred dissolved H2S over hydrosulfide anion
      (HS-), whereas HS- inhibited polysulfide production. In hypoxia, other possible
      electron donors such as nitrate, nitrite, sulfite, sulfate, thiosulfate and
      metabisulfite were ineffective. Manganese SOD also catalyzed H2S oxidation to
      form polysulfides, but did not metabolize polysulfides indicating common
      attributes of these SODs. These experiments suggest that, unlike the well-known
      SOD-mediated dismutation of two O2*- to form H2O2 and O2, SOD catalyzes a
      reaction using H2S and O2 to form persulfide. These can then combine in various
      ways to form polysulfides and sulfur oxides. It is also possible that H2S (or
      polysulfides) interact/react with SOD cysteines to affect catalytic activity or
      to directly contribute to sulfide metabolism. Our studies suggest that H2S
      metabolism by SOD may have been an ancient mechanism to detoxify sulfide or to
      regulate RSS and along with catalase may continue to do so in contemporary
      organisms.

PMID- 29220706
TI  - Swing voting in the 2016 presidential election in counties where midlife
      mortality has been rising in white non-Hispanic Americans.
AB  - Understanding the effects of widespread disruption of the social fabric on public
      health outcomes can provide insight into the forces that drive major political
      realignment. Our objective was to estimate the association between increases in
      mortality in middle-aged non-Hispanic white adults from 1999 to 2005 to 2009
      2015, health inequalities in life expectancy by income, and the surge in support
      for the Republican Party in pivotal US counties in the 2016 presidential
      election. We conducted a longitudinal ecological study in 2764 US counties from
      1999 to 2016. Increases in mortality were measured using age-specific (45-54
      years of age) all-cause mortality from 1999 to 2005 to 2009-2015 at the county
      level. Support for the Republican Party was measured as the party's vote share in
      the presidential election in 2016 adjusted for results in 2008 and 2012. We found
      a significant up-turn in mortality from 1999 to 2005 to 2009-2015 in counties
      where the Democratic Party won twice (2008 and 2012) but where the Republican
      Party won in 2016 (+10.7/100,000), as compared to those in which the Democratic
      Party won in 2016 (-15.7/100,000). An increase in mortality of 15.2/100,000 was
      associated with a significant (p < 0.001) 1% vote swing from the 2008-2012
      average to 2016. We also found that counties with wider health inequalities in
      life expectancy were more likely to vote Republican in 2016, regardless of the
      previous voting patterns. Counties with worsening premature mortality in the last
      15 years and wider health inequalities shifted votes toward the Republican Party
      presidential candidate. Further understanding of causes of unanticipated
      deterioration in health in the general population can inform social policy.

PMID- 29220705
TI  - Therapeutic landscapes and longevity: Wellness tourism in Bama.
AB  - Due to the rising demand for healthcare products and concern over environmental
      pollution, wellness tourism has been booming in China in recent years. The
      therapeutic landscape theory provides a multi-scale interpretation of wellness
      tourism to explore how wellness tourists achieve health in healing places. By
      presenting the results of 83 interviews conducted in Bama, China, this study
      reveals that the "longevity village" Bama, endorsed by centenarians, provides a
      retreat that combines natural beauty and a harmonious neighbourhood for wellness
      tourists. This article argues that although three themes-natural environment,
      social interaction and symbolic landscape-work together in the healing process of
      tourists, the symbolic landscape, which is significantly shaped by the longevity
      culture, plays a dominant role. Longevity in Chinese culture symbolizes the
      alignment of a strong body, graceful mind, and pleasant habitat. Furthermore,
      tourism reinforces the importance of symbols and imagination (of a place), the
      perception of longevity demonstrates the symbolic landscape and thus increases
      tourists' attachment to the place, and the unusual environment leads to a
      different therapeutic landscape from that of daily life. Finally, since to date
      there has been very few works on therapeutic landscapes in China, it is expected
      that this study will fill the knowledge gap and broaden the scope of application
      as well as conceptualization of the therapeutic landscape.

PMID- 29220698
TI  - Synergistic interaction of fatty acids and oxysterols impairs mitochondrial
      function and limits liver adaptation during nafld progression.
AB  - The complete mechanism accounting for the progression from simple steatosis to
      steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been
      elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty
      acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to
      oxysterols during oxidative stress conditions. We hypothesize that interaction of
      FAs and cholesterol derivatives may primarily impair mitochondrial function and
      affect biogenesis adaptation during NAFLD progression. We demonstrated that the
      accumulation of specific non-enzymatic oxysterols in the liver of animals fed
      high-fat+high-cholesterol diet induces mitochondrial damage and depletion of
      proteins of the respiratory chain complexes. When tested in vitro, 5alpha
      cholestane-3beta,5,6beta-triol (triol) combined to FFAs was able to reduce
      respiration in isolated liver mitochondria, induced apoptosis in primary
      hepatocytes, and down-regulated transcription factors involved in mitochondrial
      biogenesis. Finally, a lower protein content in the mitochondrial respiratory
      chain complexes was observed in human non-alcoholic steatohepatitis. In
      conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols
      synergistically facilitates development and progression of NAFLD by impairing
      mitochondrial function, energy balance and biogenesis adaptation to chronic
      injury.

PMID- 29220707
TI  - Hunter-gatherer health and development policy: How the promotion of sedentism
      worsens the Agta's health outcomes.
AB  - Many hunter-gatherer groups live on the outskirts of wider society, experiencing
      poor health outcomes with little access to medical care. From a development
      perspective, key interventions include the sedentarisation of these mobile
      peoples into camps nearby larger towns with sanitation infrastructure and medical
      care, as increased access to services is assumed to improve outcomes. However,
      recent research in the Agta (Philippine foragers from North-east Luzon) has
      demonstrated that individuals residing in more 'developed' communities suffer
      from increased morbidity and mortality. Here, using quantitative and ethnographic
      data on health collected between 2002 and 2014, we explore why this trend occurs
      by examining the relationship between key development initiatives with self
      reported illness and the uptake of medical interventions with 415 Agta men, women
      and children. We demonstrate that health outcomes worsen as sedentarisation
      progresses, despite some increases in medical access. We argue this is because
      the development paradigm is not evidence-based, but rather stems from an
      ideological dislike of mobile hunter-gatherer lifestyles. Compounded by cultural
      insensitivity and daily discrimination, current interventions are ill-suited to
      the unique needs of hunter-gatherers, and thus ineffective. Based on our findings
      we offer future short and long-term policy suggestions which seek to reduce the
      Agta's vulnerability, rather than increase it.

PMID- 29220710
TI  - Life satisfaction and its associated factors among money boys in China.
AB  - OBJECTIVES: Money Boy (MB) is a unique term used in China referring to a
      specialized population of men who sell sex to other men. Life satisfaction can
      influence one's health-related behaviors. The aim of our study was to find out
      the situation of MBs' life satisfaction and its associated factors. STUDY DESIGN:
      A cross-sectional study among MBs was conducted between July and December 2013 in
      Hunan province, China. METHODS: Respondent-driven sampling method was used for
      recruitment, with the initial seven 'seeds' found from a gay dating website, and
      234 participants were enrolled into the study. They were asked to complete a
      questionnaire about their demographic characteristics, work experience as MB,
      family environment, health-related behaviors, status of self-esteem, self-stigma,
      and perceived life satisfaction. Descriptive statistics and multiple linear
      regression analysis were applied. RESULTS: There were 205 valid questionnaires
      collected. The results showed that MBs' life satisfaction score was 17.9 +/- 6.3.
      The multiple linear regression model identified five factors correlated with MBs'
      life satisfaction. Three factors were found to be positively correlated with life
      satisfaction, consistent condom use with clients (beta = 3.093, P = 0.010),
      interpersonal relationship (beta = 1.027, P = 0.017), and self-esteem (beta =
      0.253, P = 0.005). And two factors were found to be negatively correlated with
      life satisfaction, seeking for clients through mommy's arrangement (beta = 
      2.091, P = 0.019) and had ever gotten at least one kind of sexually transmitted
      disease (STDs) (beta = -1.971, P = 0.034). CONCLUSIONS: The present study
      contributed to a better understanding of MBs' life satisfaction and behavioral
      and other psychosocial features. It is suggested that comprehensive interventions
      involving behavioral and psychosocial health promotion approaches are needed for
      this population. Those programs will be more acceptable among this group and tend
      to be sustainable.

PMID- 29220712
TI  - Characteristics of Romanian women who enrolled in a postpartum tobacco smoking
      relapse prevention trial.

PMID- 29220709
TI  - Self-reported influenza vaccination rates and attitudes towards vaccination among
      health care workers: results of a survey in a German university hospital.
AB  - OBJECTIVES: The objective of this survey was to analyse vaccination rates and
      attitudes towards vaccination among health care workers (HCWs). The period
      prevalence of self-reported acute respiratory infections in the influenza season
      2014/2015 was examined. STUDY DESIGN: A cross-sectional study was conducted among
      HCWs of a German university hospital using an anonymised questionnaire.
      Recruitment was performed by providing all medical and nursing staff a paper
      questionnaire with an invitation to participate. METHODS: Descriptive aggregated
      data were generated from digitalised questionnaires for all variables.
      Differences in categorical variables were analysed by Chi-squared test. Textual
      data were analysed by an iterative process based on the grounded theory by Glaser
      and Strauss. RESULTS: The response rate was 31% (677/2186). Probable influenza
      was described by 9% (64/677) of the participants. The overall self-reported
      vaccination rate was 55% (366/666). Self-reported vaccination rate was higher in
      physicians (172/239, 72%) than in nursing staff (188/418, 45%). HCWs in
      paediatrics (103/148, 70%) more likely received vaccines than HCWs in surgery
      (31/84, 37%). Most vaccinations were provided by medical staff on the wards
      (164/368, 45%). Self-reported lost work-time due to adverse events after
      vaccination was low (6/336, 2%). Eight categories for vaccine refusal were
      identified, whereof doubts about effectiveness and indication of the vaccine was
      most frequently mentioned (72/202, 36%). CONCLUSIONS: Efforts to promote
      vaccination should focus on nursing staff and should provide scientific evidence
      on effectiveness, adverse effects, and the benefits of health care workers'
      vaccination for patients. Administering vaccines at the workplace proved to be a
      successful strategy in our setting. Studies are needed to assess the frequency of
      influenza causing disease in HCWs.

PMID- 29220708
TI  - Comparative diagnostic accuracy of dual-energy CT myocardial perfusion imaging by
      monochromatic energy versus material decomposition methods.
AB  - PURPOSE: To compare the diagnostic value of monochromatic and material
      decomposition (MD) dual- energy computed tomography (DECT) imaging for the
      evaluation of ischemia. METHODS: Patients with suspected coronary artery disease
      underwent rest-stress DECT and SPECT perfusion imaging. DECT images were
      reconstructed between 40 and 140keV and through MD of iodine/muscle. RESULTS: MD
      and monochromatic imaging had a sensitivity, specificity, negative predictive,
      positive predictive value, and accuracy of 89%, 40%, 67%, 73% and 71%; and 91%,
      67%, 67%, 91% and 86%, respectively (p=0.05). CONCLUSION: DECT using
      monochromatic energy displayed a non-significantly higher diagnostic accuracy for
      myocardial ischemia as compared with DECT MD.

PMID- 29220713
TI  - In vitro models for deciphering the mechanisms underlying the sexual transmission
      of viruses at the mucosal level.
AB  - Sexually transmitted viruses infect the genital and colorectal mucosa of the
      partner exposed to contaminated genital secretions through a wide range of
      mechanisms, dictated in part by the organization of the mucosa. Because
      understanding the modes of entry into the organism of viruses transmitted through
      sexual intercourse is a necessary prerequisite to the design of treatments to
      block those infections, in vitro modeling of the transmission is essential. The
      aim of this review is to present the models and methodologies available for the
      in vitro study of the interactions between viruses and mucosal tissue and for the
      preclinical evaluation of antiviral compounds, and to point out their advantages
      and limitations according to the question being studied.

PMID- 29220714
TI  - Mapping of radiation anomalies using UAV mini-airborne gamma-ray spectrometry.
AB  - Localization of size-limited gamma-ray anomalies plays a fundamental role in
      uranium prospecting and environmental studies. Possibilities of a newly developed
      mini-airborne gamma-ray spectrometric equipment were tested on a uranium anomaly
      near the village of Trebsko, Czech Republic. The measurement equipment was based
      on a scintillation gamma-ray spectrometer specially developed for unmanned aerial
      vehicles (UAV) mounted on powerful hexacopter. The gamma-ray spectrometer has two
      103 cm3 BGO scintillation detectors of relatively high sensitivity. The tested
      anomaly, which is 80 m by 40 m in size, was investigated by ground gamma-ray
      spectrometric measurement in a detail rectangular measurement grid. Average
      uranium concentration is 25 mg/kg eU attaining 700 mg/kg eU locally. The mini
      airborne measurement across the anomaly was carried out on three 100 m long
      parallel profiles at eight flight altitudes from 5 to 40 m above the ground. The
      resulting 1 s 1024 channel gamma-ray spectra, recorded in counts per second
      (cps), were processed to concentration units of K, U and Th, while total count
      (TC) was reported in cps. Increased gamma ray intensity of the anomaly was
      indicated by mini-airborne measurement at all profiles and altitudes, including
      the highest altitude of 40 m, at which the recorded intensity is close to the
      natural radiation background. The reported instrument is able to record data with
      comparable quality as standard airborne survey, due to relative sensitive
      detector, lower flight altitude and relatively low flight speed of 1 m/s. The
      presented experiment brings new experience with using unmanned semi-autonomous
      aerial vehicles and the latest mini-airborne radiometric instrument. The
      experiment has demonstrated the instrument's ability to localize size-limited
      uranium anomalies.

PMID- 29220715
TI  - Getting to know you: The development of mechanisms underlying face learning.
AB  - Nearly every study investigating the development of face recognition has focused
      on the ability to tell people apart using one or two tightly controlled images to
      represent each identity. Such research ignores the challenge of recognizing the
      same person despite variability in appearance. Whereas natural variation in
      appearance makes unfamiliar faces difficult to recognize, by 6 years of age
      people easily recognize multiple images of familiar faces. Two mechanisms are
      proposed to underlie the process by which adults become familiar with newly
      encountered faces. We provide the first examination of the development of these
      mechanisms during childhood (6-11 years). In Experiment 1, we examined children's
      (6- to 10-year-olds') and adults' ability to engage in ensemble coding-the
      ability to rapidly extract an average representation of an identity from several
      instances. In Experiment 2, we examined children's ability to use within-person
      variability in appearance to recognize novel instances of a newly encountered
      identity. We created a child-friendly perceptual matching task, and the number of
      images to which participants were exposed varied across targets. Although
      children were less accurate than adults overall in Experiment 2, we found no age
      related improvement in either ensemble coding or the ability to benefit from
      exposure to within-person variability in appearance when learning a new face,
      suggesting that both abilities are developed by 6 years of age. We discuss the
      implications of these findings for understanding the nature of mechanisms
      underlying face learning and other developmental processes such as language and
      music.

PMID- 29220711
TI  - Association between water fluoride and the level of children's intelligence: a
      dose-response meta-analysis.
AB  - OBJECTIVES: Higher fluoride concentrations in water have inconsistently been
      associated with the levels of intelligence in children. The following study
      summarizes the available evidence regarding the strength of association between
      fluoridated water and children's intelligence. STUDY DESIGN: Meta-analysis.
      METHODS: PubMed, Embase, and Cochrane Library databases were systematically
      analyzed from November 2016. Observational studies that have reported on
      intelligence levels in relation to high and low water fluoride contents, with 95%
      confidence intervals (CIs) were included. Further, the results were pooled using
      inverse variance methods. The correlation between water fluoride concentration
      and intelligence level was assessed by a dose-response meta-analysis. RESULTS:
      Twenty-six studies reporting data on 7258 children were included. The summary
      results indicated that high water fluoride exposure was associated with lower
      intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to 
      0.42; P < 0.001). The findings from subgroup analyses were consistent with those
      from overall analysis. The dose-response meta-analysis suggested a significant
      association between water fluoride dosage and intelligence (P < 0.001), while
      increased water fluoride exposure was associated with reduced intelligence
      levels. CONCLUSIONS: Greater exposure to high levels of fluoride in water was
      significantly associated with reduced levels of intelligence in children.
      Therefore, water quality and exposure to fluoride in water should be controlled
      in areas with high fluoride levels in water.

PMID- 29220717
TI  - Microbial electricity driven anoxic ammonium removal.
AB  - Removal of nitrogen, mainly in form of ammonium (NH4+), in wastewater treatment
      plants (WWTPs) is a highly energy demanding process, mainly due to aeration. It
      causes costs of about half a million Euros per year in an average European WWTP.
      Alternative, more economical technologies for the removal of nitrogen compounds
      from wastewater are required. This study proves the complete anoxic conversion of
      ammonium (NH4+) to dinitrogen gas (N2) in continuously operated
      bioelectrochemical systems at the litre-scale. The removal rate is comparable to
      conventional WWTPs with 35 +/- 10 g N m-3 d-1 with low accumulation of NO2-, NO3
      , N2O. In contrast to classical aerobic nitrification, the energy consumption is
      considerable lower (1.16 +/- 0.21 kWh kg-1 N, being more than 35 times less than
      for the conventional wastewater treatment). Biotic and abiotic control
      experiments confirmed that the anoxic nitrification was an electrochemical
      biological process mainly performed by Nitrosomonas with hydroxylamine as the
      main substrate (mid-point potential, Eox = +0.67 +/- 0.08 V vs. SHE). This
      article proves the technical feasibility and reduction of costs for ammonium
      removal from wastewater, investigates the underlying mechanisms and discusses
      future engineering needs.

PMID- 29220716
TI  - Self-accelerating sulfur reduction via polysulfide to realize a high-rate
      sulfidogenic reactor for wastewater treatment.
AB  - Sulfur reduction is a promising alternative to sulfate reduction as it can
      generate sulfide at a low cost for the precipitation of heavy metals or
      autotrophic denitrification in wastewater treatment. However, the extremely low
      water solubility of elemental sulfur limits its bioavailability and results in a
      low sulfur-reduction rate. Polysulfide, which is naturally generated through
      reactions between sulfur and sulfide, can enhance the bioavailability of sulfur
      and thus contribute to high-rate sulfur reduction. Based on this principle, a
      laboratory-scale sulfur-reducing bioreactor was designed in this study for
      wastewater treatment. After 164 days of operation, the sulfide production rate
      (SPR) in the bioreactor reached 126 mg S/L-h, which is significantly higher than
      those of other sulfate-reducing systems. Moreover, dissolved zero-valent sulfur
      (referred to as polysulfide) was detected in the sulfur-reducing reactor when the
      organics were completely depleted, indicating that polysulfide can form naturally
      and be readily reduced to sulfide in the bioreactor. We found that the produced
      sulfide promoted the formation of more polysulfide, which enabled a self
      accelerating chain reaction of sulfur reduction via polysulfide. This stimulation
      effect was further validated by the 7-h batch tests. In the batch test without
      sulfide addition initially, a continuous increase in the hourly SPR was observed
      with increasing sulfide concentration. Furthermore, in the batch tests with the
      addition of 50-200 mg S/L sulfide at the beginning, the average SPR in the first
      3 h increased with elevating initial sulfide concentration due to more
      polysulfide formation and reduction. However, high sulfide concentration (>250 mg
      S/L) hindered the continuous increase in SPR. Additionally, when polysulfide
      formation was prevented through the addition of Fe2+, the SPR dropped by 97.6%
      compared to that in the presence of polysulfide. This validates the key role of
      polysulfide in the high-rate sulfur reduction process. Overall, the findings
      suggest that high-rate sulfur reduction can be achieved for autotrophic
      denitrification or heavy-metal removal in wastewater treatment.

PMID- 29220699
TI  - HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via
      mitochondrial ROS production.
AB  - Human immunodeficiency virus (HIV) infection is associated with B-cell
      malignancies in patients though HIV-1 is not able to infect B-cells. The rate of
      B-cell lymphomas in HIV-infected individuals remains high even under the combined
      antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the
      contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces
      oxidative stress and DNA damage in infected cells via multiple mechanisms,
      including viral Tat protein. We have detected elevated levels of reactive oxygen
      species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is
      present in blood of infected individuals and is able to transduce cells, we
      hypothesized that it could induce oxidative DNA damage in B-cells promoting
      genetic instability and malignant transformation. Indeed, incubation of B-cells
      isolated from healthy donors with purified Tat protein led to oxidative stress, a
      decrease in the glutathione (GSH) levels, DNA damage and appearance of
      chromosomal aberrations. The effects of Tat relied on its transcriptional
      activity and were mediated by NF-kappaB activation. Tat stimulated oxidative
      stress in B-cells mostly via mitochondrial ROS production which depended on the
      reverse electron flow in Complex I of respiratory chain. We propose that Tat
      induced oxidative stress, DNA damage and chromosomal aberrations are novel
      oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals.

PMID- 29220720
TI  - Induction of thymic stromal lymphopoietin by a steroid alkaloid derivative in
      mouse keratinocytes.
AB  - Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and
      exacerbating allergic diseases. Chemical compounds that induce TSLP production
      can enhance sensitization to antigens and exacerbate allergic inflammation.
      Hence, identifying such chemicals will be important to prevent an increase in
      allergic diseases. In the present study, we found, for the first time, that a
      steroid alkaloid derivative, code no. 02F04, concentration and time dependently
      induced mRNA expression and production of TSLP in a mouse keratinocyte cell line,
      PAM212. In particular, the activity of 02F04 was selective to TSLP. As an
      analogue of the liver X receptor (LXR) endogenous ligand, 02F04 rapidly increased
      ATP-binding cassette transporter A1 (ABCA1) expression by regulating the nuclear
      receptor of LXR. However, instead of being inhibited by the LXR antagonist, 02F04
      induced TSLP production was delayed and markedly suppressed by inhibitors of
      phospholipase C (PLC), pan-protein kinase C (PKC), PKCdelta, Rho-associated
      protein kinase (ROCK), extracellular signal-regulated kinase (ERK) 1/2, and
      IkappaBeta kinase 2 (IKK2). Treatment with 02F04 caused the formation of F-actin
      filaments surrounding the nucleus of PAM212 cells, which then disappeared
      following addition of ROCK inhibitor. 02F04 also induced phosphorylation of
      ERK1/2 from 2h after treatment, with a maximum at 24h, and increased nuclear
      factor-kappaB (NF-kappaB) promoter activity by 1.3-fold. Taken together, these
      results indicate that 02F04-induced TSLP production is regulated via distinct
      signal transduction pathways, including PLC, PKC, ROCK, ERK1/2, and NF-kappaB but
      not nuclear receptors. 02F04, with a unique skeletal structure in inducing TSLP
      production, can represent a potential new tool for investigating the role of TSLP
      in allergic diseases.

PMID- 29220724
TI  - Pharmacokinetics of a novel triazine ethanamizuril in rats and broiler chickens.
AB  - Ethanamizuril is a new triazine compound that displays potent anticoccidial
      activity against chicken coccidiosis caused by Eimeria tenella. We studied the
      pharmacokinetics of ethanamizuril in rats and chickens after single oral doses of
      one, two and three times the minimum effective dose Ethanamizuril was readily
      absorbed at all three doses and the plasma concentration reached was maximal
      within 5h and progressively declined over time. The mean peak plasma
      concentrations (Cmax) and the area under the concentration-time curve (AUC) were
      both dose-dependent. These results provide pharmacokinetic profiles of
      ethanamizuril for future preclinical studies and clinical use.

PMID- 29220719
TI  - House dust mite allergen causes certain features of steroid resistant asthma in
      high fat fed obese mice.
AB  - Obesity is a high risk factor for diseases such as cardiovascular, metabolic
      syndrome and asthma. Obese-asthma is another emerging phenotype in asthma which
      is typically refractive to steroid treatment due to its non-classical features
      such as non-eosinophilic cellular inflammation. The overall increased morbidity,
      mortality and economical burden in asthma is mainly due to steroid resistant
      asthma. In the present study, we used high fat diet induced obese mice which when
      sensitized with house dust mite (HDM) showed steroid resistant features. While
      the steroid, dexamethasone (DEX), treatment to high fat fed naive mice could not
      reduce the airway hyperresponsiveness (AHR) induced by high fat, DEX treatment to
      high fat fed allergic mice could not reduce the HDM allergen induced airway
      remodeling features though it reduced airway inflammation. Further, these HDM
      induced high fat fed mice with or without DEX treatment had shown the increased
      activity and expression of arginase as well as the inducible nitric oxide
      synthase (iNOS) expression. However, DEX treatment had reduced the expressions of
      high iNOS and arginase I in control chow diet fed mice. Thus, we speculate that
      the steroid resistance seen in human obese asthmatics could be stemming from
      altered NO metabolism and its induced airway remodeling and with further
      investigations, it would encourage new treatments specific to obese-asthma
      phenotype.

PMID- 29220723
TI  - Gold nanoparticles enhance radiation sensitization and suppress colony formation
      in a feline injection site sarcoma cell line, in vitro.
AB  - Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that
      are frequently associated with routine vaccination. Current treatment modalities
      include chemotherapy, radiation, and radical surgery. ISS have been shown to be
      one of the most treatment resistant of feline cancers with high rates of
      recurrence. Previous studies have shown that gold and other high atomic number
      nanoparticles have the ability to increase the dose of radiation deposited into
      tissue by generating secondary electrons. The focus of the current study was to
      assess the effects of gold nanoparticles (AuNP) on ISS cytotoxicity and colony
      formation both as a standalone treatment and in combination with electron beam
      radiation. Cells from an established ISS cell line were co-cultured with 15nm
      AuNP at 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0mM. AuNP cytotoxicity was evaluated by
      assessing changes in cellularity, cell proliferation, cell cycle and
      viability/apoptosis/necrosis. The radiosensitizing potential of AuNP on ISS
      replication was assessed by the clonogenic assay. AuNP were found to
      significantly decrease cellular proliferation. However, the acute viability and
      cell cycle of ISS was not significantly altered. Interestingly, AuNP alone were
      shown to significantly impair colony formation. In the presence of 9MeV electron
      radiation, AuNP numerically decreased colony formation in ISS cells compared to
      cells treated with radiation only. AuNP may have efficacy as a long term
      therapeutic agent for decreasing ISS growth.

PMID- 29220725
TI  - Sparse-view neutron-photon computed tomography: Object reconstruction and
      material discrimination.
AB  - Taking into account the advantages of both neutron- and photon-based systems, we
      propose combined neutron-photon computed tomography (CT) under a sparse-view
      setting and demonstrate its performance for 3D object visualization and material
      discrimination. We use a high-performance regularization method for CT
      reconstruction by combining regularization based on total variation (TV) and
      curvelet transform in cone beam geometry. It is coupled with proposed 2D material
      signatures which is pairs of photon to neutron transmission ratios and neutron
      transmission values per object space voxels. Classification of materials is
      performed by association of a voxel signature with library signatures; and per
      object - by majority of voxels in the object. Representation of object-material
      pairs, for the model in our experiment, a complex scene with group of high-Z and
      low-Z materials, attains the reconstruction accuracy of 92.1% and the overall
      high-Z discrimination accuracy of object representation is 85%, and by about 7.5%
      higher discrimination accuracy than that with 1D signatures which are ratios of
      photon to neutron transmissions. With a relative noise level of 10%, the method
      yields the reconstruction accuracies of 87.2%. The analyses are performed in cone
      beam configuration, with Monte Carlo modeling of neutron-photon transport for the
      model of object geometry and material contents.

PMID- 29220721
TI  - Novel effect of methionine enkephalin against influenza A virus infection through
      inhibiting TLR7-MyD88-TRAF6-NF-kappaB p65 signaling pathway.
AB  - The morbidity and mortality associated with influenza A virus infections, have
      stimulated the search for novel prophylactic and therapeutic drugs. The purpose
      of this study was to investigate the prophylactic and therapeutic effect of
      synthetic methionine enkephalin (MENK) on mice infected by A/PR/8/34 influenza
      virus (H1N1) in vivo. The results showed that MENK could exert both prophylactic
      and therapeutic influences on infected mice, significantly improve the survival
      rate, relieve acute lung injury and decrease cytokine (IFN-alpha, IFN-beta, TNF
      alpha, IL-6, and IL-1beta) levels. MENK also inhibited virus replication on day 4
      post infection (p.i.) through upregulating opioid receptors (MOR, DOR) and
      suppressing TLR7-MyD88-TRAF6-NF-kappaB p65 signaling pathways. These results
      suggest that MENK, given via intranasal administration, could provide a novel
      drug with a new mode of action as a nonspecific anti-influenza agent or vaccine
      adjuvant.

PMID- 29220726
TI  - Monte Carlo calculations of electrons impinging on a copper target: A comparison
      of EGSnrc, Geant4 and MCNP5.
AB  - A simple geometry is used to compare several of the available Monte Carlo
      software codes for radiation transport. EGSnrc, Geant4 and MCNP5 are all used to
      calculate the photon fluence produced from electrons incident on a copper target.
      Four energies for the isotropic point source are chosen to simulate the average
      and maximum emission energies of 32P and 90Y: (0.7, 1.71)MeV and (0.93, 2.28)MeV,
      respectively. The energy deposition in the copper target, the electron current at
      the target and the computational efficiency are also calculated. EGSnrc is found
      to be the only self-consistent code when comparing results calculated using the
      default transport parameters of the condensed history mode with those calculated
      in the single scattering mode.

PMID- 29220722
TI  - Circulating miRNAs expression profiling in drug-resistant epilepsy: Up-regulation
      of miR-301a-3p in a case of sudden unexpected death.
AB  - Sudden and unexpected death in epilepsy (SUDEP) represents one of the most
      challenging fields for clinical, forensic and preventative pathology. Several
      authors have emphasized the search of innovative biomarkers related to drug
      resistance for an appropriate risk stratification in these patients. However, no
      reliable biomarker has been implemented into clinical practice, so far. Herein,
      we present a case of SUDEP due to drug-resistant mesial temporal lobe epilepsy
      (MTLE) in which we performed miRNA expression profiling (miR-301a-3p, miR-194-5p,
      miR-30b-5p, mIR-342-5p, and miR-4446-3p) from both the plasma and the temporal
      lobe in comparison to ten autopsies for traumatic or asphyxia deaths. A
      significant up-regulation of miR-301a-3p in both the plasma (2.3 increase vs.
      controls) and the hippocampus (3.2-fold increase vs. controls) was evidenced,
      whereas the other tested miRNAs showed no significant expression differences
      between case and controls. Even preliminary, our results support miRNAs as an
      innovative class of biomarkers compatible with an adequate analysis of
      biospecimens obtained from forensic autopsies.

PMID- 29220728
TI  - Assessment of long-term exposure to airborne dioxin and cadmium concentrations in
      the Lyon metropolitan area (France).
AB  - Identifying the long-term effects of airborne pollutants requires the computation
      of the spatial and temporal variability of their concentration in air to estimate
      the exposure of the population. To estimate exposure levels of individuals in a
      breast cancer case control study nested in a national prospective cohort, we
      determine here the differential impact of a variety of cadmium and dioxin sources
      on urban air over a large urban area and over a period of almost 20years. To that
      end, we couple an emission model, to estimate dioxin and cadmium atmospheric
      annual releases, with an urban dispersion model in order to compute pollutant
      concentration fields at a fine temporal (1h) and spatial (25m) resolution. The
      reliability of the modelling chain is compared to two types of measurement: i)
      localized industrial emissions and ii) dioxin and cadmium air monitoring data
      (from 2007 to 2008), collected at a fixed station, placed in the city centre, as
      well as at three mobile short-term dioxin monitoring stations, located in the
      suburbs (the latter providing dioxin data, only). Comparisons between measured
      and estimated emissions show non-negligible difference, with a correlations for
      dioxin (rs=0.42) and cadmium (rs=0.41). Despite this, mean values between
      estimated emissions and emission measurements are close to each other, in
      particular for cadmium. Weekly average modelled concentrations show an overall
      good agreement with weekly average measured concentrations in spring and summer
      but are generally lower than monitored data in winter due to peak concentrations
      from diffuse sources representing an important proportion of emissions in
      2007/2008. The model provides better results for cadmium than for dioxin. Despite
      the relevant errors in the model predictions, the model meets the validation
      criteria, defined by Chang and Hanna for an urban dispersion model. Simulation
      scenarios of air pollutant concentrations, reconstructed over the last 20years,
      show the effects of the variability of the pollutant sources over time with
      decreasing levels of dioxin and cadmium concentrations in air. This is primarily
      due to the reduction in localized industrial releases, which results in a general
      trend of homogenization of the exposure of the population. The model further
      allows us to dissociate the contribution of different types of pollutant sources
      on the population exposure. The impact on local concentrations due to industrial
      emissions, which were originally responsible for the major impact on air quality,
      is shown to drop over the years by 99% and 92% for dioxin and cadmium,
      respectively. Today, the major contributions are due to diffuse miscellaneous
      sources in the case of dioxin and to traffic-related emissions for cadmium.
      Average modelled concentrations at the study subjects' residential locations
      range from 10.2 to 82.1fg-TEQ/m3 for dioxin and 0.10 to 1.6ng/m3 for cadmium and
      are comparable with data from the literature. The study results will be essential
      to increase the accuracy of the assessment of long-term airborne dioxin and
      cadmium exposure and improve the results of epidemiological studies.

PMID- 29220731
TI  - Quantitative texture analysis in the prediction of IDH status in low-grade
      gliomas.
AB  - OBJECTIVES: Molecular markers provide valuable information about treatment
      response and prognosis in patients with low-grade gliomas (LGG). In order to make
      this important information available prior to surgery the aim of this study was
      to explore if molecular status in LGG can be discriminated by preoperative
      magnetic resonance imaging (MRI). PATIENTS AND METHODS: All patients with
      histopathologically confirmed LGG with available molecular status who had
      undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra
      scanner during 2008-2015 were retrospectively identified. Based on Haralick
      texture parameters and the segmented LGG FLAIR volume we explored if it was
      possible to predict molecular status. RESULTS: In total 25 patients (nine women,
      average age 44) fulfilled the inclusion parameters. The textural parameter
      homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR
      0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p=0.005). None of the other
      four analyzed texture parameters (energy, entropy, correlation and inertia) were
      associated with molecular status. Using ROC curves, the area under curve for
      predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and
      0.940 for the combined parameters of tumor volume and homogeneity. We could not
      predict molecular status using the four other chosen texture parameters (energy,
      entropy, correlation and inertia). Further, we could not separate LGG with IDH
      mutation with or without 1p19q codeletion. CONCLUSIONS: In this preliminary study
      using Haralick texture parameters based on preoperative clinical FLAIR sequence,
      the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG.
      Combined with tumor volume, these diagnostic properties seem promising.

PMID- 29220729
TI  - Comparison of dynamic cervical implant versus anterior cervical discectomy and
      fusion for the treatment of single-level cervical degenerative disc disease: A
      five-year follow-up.
AB  - OBJECTIVE: To compare clinical and radiographic outcomes of dynamic cervical
      implant(DCI) with anterior cervical discectomy and fusion(ACDF) in the treatment
      of single-level cervical degenerative disc disease (CDDD) 5 years after surgery.
      PATIENTS AND METHODS: Forty-three patients with DCI were matched one-to-one with
      patients with ACDF based on age, gender, and operative segment in this
      retrospective study. All patients had been followed up for more than 5 years.
      Radiological assessments included heterotopic ossification(HO), adjacent segment
      degeneration (ASD), intervertebral height (IH), range of motion (ROM) at C2-7,
      the implanted level and adjacent levels. Clinical parameters included Visual
      Analogue Scale (VAS), Japanese Orthopedic Association (JOA) scores, Neck
      Disability Index (NDI) and Short Form-36 scores(SF-36). Patients were also asked
      to rate their postoperative satisfaction at final follow-up. RESULTS: The
      postoperative ROM of C2-7 and ROM at the implanted level in the DCI group were
      higher than those in the ACDF group. The ROM at the implanted level in the DCI
      group was maintained at 2 years postoperatively but decreased at final follow-up
      (10.7 degrees  vs 4.5 degrees ). The rate of HO in the DCI group was 46.5%
      (20/43). The rate of ASD was comparable between the two groups (16.3% vs 20.9%).
      The JOA, VAS, NDI, and SF-36 scores were comparable between two groups and
      improved postoperatively. However, the proportion of patients who reported their
      level of satisfaction as being very satisfied, or somewhat satisfied was larger
      in the ACDF group than that in the DCI group (95.3% vs 79.1%). CONCLUSIONS: DCI
      resulted in better ROM of C2-7 and the implanted level than ACDF did. The
      clinical outcomes were similar between two groups. However, the ROM at the
      implanted level decreased at final follow-up in the DCI group, which may
      contribute to patient dissatisfaction. The long-term outcomes were not that
      satisfactory especially due to the deviation from its original intention as a non
      fusion technique. As such, we have not used DCI in the past 2 years.

PMID- 29220737
TI  - Rheumatology nurse specialists and corticosteroids prescription-Is it safe?

PMID- 29220730
TI  - Effect of white matter changes on risk score for peri-procedural complications
      after carotid artery stenting.
AB  - OBJECTIVES: The presence of more severe white matter changes (WMC) may be
      associated with a higher risk of peri-procedural strokes in patients undergoing
      carotid artery stenting (CAS). However, to what extent WMC affects peri
      procedural risk of CAS is unclear. We aimed to evaluate the effect of WMC on peri
      procedural complications by modifying a CAS peri-procedural risk scale through
      adding the assessment of WMC. PATIENTS AND METHODS: A database of patients
      undergoing CAS was sampled from 2007 to 2014 in a single Chinese medical center.
      Risk factors were evaluated for peri-interventional cerebral and cardiac events
      and mortality. A risk score including contralateral stenosis >= 50%, diabetes
      with HbA1c > 7%, age >= 80 years old, symptomatic stenosis or with an ulcer
      lesion was applied to predict peri-interventional risk. Age-related white matter
      change (ARWMC) score was calculated and added to this risk scale. The predictive
      power of the new scale was evaluated. RESULTS: 151 patients were enrolled in the
      study. 14 peri-interventional events were recorded. Patients with peri-procedural
      complications had higher rates of diabetes (57.1% vs 18.2%, P = 0.001),
      contralateral stenosis (64.29% vs 32.85%, P = 0.019), coronary heart disease
      (42.9% vs 14.6%, P = 0.008) and ARWMC >= 7 (64.3% vs 25.5%, P = 0.002) compared
      with patients without peri-procedural complications. ARWMC >= 7 was an
      independent risk factor for peri-procedural complications from factors of the CAS
      scale after adjusting other confounders including contralateral stenosis >= 50%,
      HbA1c > 7%, age >= 80 years old and symptomatic stenosis or with an ulcer lesion.
      After the ARWMC score was added to the original scale, the AUC value of the new
      scale to predict the risk of peri-procedural complications after CAS was elevated
      (0.808 vs 0.730, p = 0.068). CONCLUSION: More severe WMC was a risk factor for
      peri-procedural complications after CAS in patients with carotid artery stenosis.
      ARWMC score may help to improve the predictive power of the risk scale for peri
      procedural complications after CAS.

PMID- 29220727
TI  - The health impacts of weekday traffic: A health risk assessment of PM2.5
      emissions during congested periods.
AB  - Little work has accounted for congestion, using data that reflects driving
      patterns, traffic volume, and speed, to examine the association between traffic
      emissions and human health. In this study, we performed a health risk assessment
      of PM2.5 emissions during congestion periods in the Greater Toronto and Hamilton
      Area (GTHA), Canada. Specifically, we used a micro-level approach that combines
      the Stochastic User Equilibrium Traffic Assignment Algorithm with a MOVES
      emission model to estimate emissions considering congestion conditions.
      Subsequently, we applied a concentration-response function to estimate PM2.5
      related mortality, and the associated health costs. Our results suggest that
      traffic congestion has a substantial impact on human health and the economy in
      the GTHA, especially at the most congested period (7:00am). Considering daily
      mortality, our results showed an impact of 206 (boundary test 95%: 116; 297) and
      119 (boundary test 95%: 67; 171) deaths per year (all-cause and cardiovascular
      mortality, respectively). The economic impact from daily mortality is
      approximately $1.3 billion (boundary test 95%: 0.8; 1.9), and $778 million
      (boundary test 95%: 478; 981), for all-cause and cardiovascular mortality,
      respectively. Our study can guide reliable projections of transportation and air
      pollution levels, improving the capability of the medical community to prepare
      for future trends.

PMID- 29220732
TI  - Carbon monoxide poisoning in Iran during 1999-2016: A systematic review and meta
      analysis.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning is a common cause of emergency
      department (ED) visits worldwide with high levels of morbidity and mortality. No
      inclusive nationally statistics of CO poisoning in Iran is available. The present
      review aimed to describe and review the pattern of CO poisoning in Iran. METHODS:
      The search of Medline, SCOPUS, Cochrane library, Google Scholar, Magiran, IranDoc
      and SID (Scientific Information Database) yielded only 10 studies discussing the
      epidemiology of CO poisoning in Iran. Outcomes of interest were determining the
      demographic characteristics, prevalence and mortality rates, annual trends, main
      sources and mechanisms, location of incidents of CO poisoning as well as
      providing the safety awareness and precautions. RESULTS: Totally, 10 studies
      including 6372 victims of CO poisoning were reviewed. The estimated incidence
      rate of CO poisoning was 38.91 per 100,000, the proportionate mortality rate was
      11.6 per 1000 death and the pooled case fatality rate of was 9.5% (95% CI 6.3%
      14.30%). Of the total 5105 individuals with CO poisoning, 2048 (40.12%) were male
      and 3057 (59.88%) were female. In addition, of 5105 poisoned, 4620 (90.50%) were
      alive and 485 (9.50%) were dead. The number of fatal CO poisoning cases among men
      and women were 259 (5.07%) and 226 (4.43%) victims, respectively; while the
      number of non-fatal CO poisoning cases among men and women were 1790 (35.06%) and
      2830 (55.44%) individuals, respectively. The mean age of victims was about 30
      years. Most of the victims (36.37%) had the educational level of secondary
      school, marital status of single (52.74%), and occupational status of housekeeper
      (27.48%). CONCLUSION: The incidence, proportionate mortality and case fatality
      rates of CO poisoning is high in Iran, particularly in young individuals. It
      seems that preventive strategies should be taught by health care providers more
      thoroughly and implemented by policy makers more strictly as a mandatory law.

PMID- 29220718
TI  - Spatial and temporal dynamics of pathogenic Leptospira in surface waters from the
      urban slum environment.
AB  - Leptospirosis has emerged as an important urban health problem as slum
      settlements have expanded worldwide. Yet the dynamics of the environmentally
      transmitted Leptospira pathogen has not been well characterized in these
      settings. We used a stratified dense sampling scheme to study the dynamics of
      Leptospira abundance in surface waters from a Brazilian urban slum community. We
      collected surface water samples during the dry, intermediate and rainy seasons
      within a seven-month period and quantified pathogenic Leptospira by quantitative
      PCR (qPCR). We used logistic and linear mixed models to identify factors that
      explained variation for the presence and concentration of Leptospira DNA. Among
      335 sewage and 250 standing water samples, Leptospira DNA were detected in 36%
      and 34%, respectively. Among the 236 samples with positive results geometric mean
      Leptospira concentrations were 152 GEq/mL. The probability of finding Leptospira
      DNA was higher in sewage samples collected during the rainy season when increased
      leptospirosis incidence occurred, than during the dry season (47.2% vs 12.5%,
      respectively, p = 0.0002). There was a marked spatial and temporal heterogeneity
      in Leptospira DNA distribution, for which type of water, elevation, and time of
      day that samples were collected, in addition to season, were significant
      predictors. Together, these findings indicate that Leptospira are ubiquitous in
      the slum environment and that the water-related risk to which inhabitants are
      exposed is low. Seasonal increases in Leptospira presence may explain the timing
      of leptospirosis outbreaks. Effective prevention will need to consider the
      spatial and temporal dynamics of pathogenic Leptospira in surface waters to
      reduce the burden of the disease.

PMID- 29220735
TI  - Regulation of sulfur deprivation-induced expression of the ferredoxin-encoding
      FDX5 gene Chlamydomonas reinhardtii in aerobic conditions.
AB  - The unicellular green alga Chlamydomonas reinhardtii reacts to sulfur (S)
      starvation with the increased expression of numerous genes. One gene which is
      induced in illuminated anaerobic S-deprived cells is the ferredoxin-5 gene
      (FDX5). To test FDX5 transcriptional regulation in aerobic cultures, we used a
      real-time PCR analysis and an artificial microRNA approach. We demonstrated that
      FDX5 gene is controlled by S deprivation independently of anoxia-treatment. The
      Ser/Thr kinase SNRK2.1 is necessary for expression of FDX5 during deprivation to
      S. Copper response regulator 1 (CRR1) is not involved in FDX5 up-regulation in S
      deficient cells under aerobic conditions. Furthermore, expression of FDX5 is
      negatively regulated by nitric oxide (NO). Moreover, truncated hemoglobin 1
      (THB1) underexpression resulted in the decrease in FDX5 transcript abundance in S
      deficient cells under aerobic conditions. Together, our results imply that the
      FDX5 gene is controlled by NO in THB1-dependent pathway under conditions of
      depleted S supply.

PMID- 29220739
TI  - Lonelier than ever? Loneliness of older people over two decades.
AB  - To live with feelings of loneliness has negative implications for quality of
      life, health and survival. This study aimed to examine changes in loneliness
      among older people, both with regard to prevalence rates, and socio-demographic,
      social and health-related correlates of loneliness. This study had a repeated
      cross-sectional design and was based on the nationally representative Swedish
      Panel Study of Living Conditions of the Oldest Old (SWEOLD). Analyses of trends
      in loneliness covered the years 1992, 2002, 2004, 2011 and 2014, and included
      people aged 77 years or older (n=2 572). Analyses of correlates of loneliness
      covered 2004 and 2014, and included people aged 70 years or older (n=1 962).
      Logistic regression analyses were conducted with findings presented as average
      marginal effects. Contrary to what is often assumed, there has been no increase
      in loneliness among older people over time (1992-2014). Regression analyses for
      2004 and 2014 showed that social and health-related correlates were more strongly
      associated with loneliness than socio-demographic correlates. Psychological
      distress was most strongly associated with loneliness, followed by widowhood.
      Most associations between the correlates and loneliness were stable over time.

PMID- 29220736
TI  - Arsenic stress effects on root water absorption in soybean plants: Physiological
      and morphological aspects.
AB  - Soybean (Glycine max L.) is often cultivated in areas contaminated with arsenic
      (As), which negatively affects plant growth and reduces crop yield. The
      deleterious effects may be due, at least in part, to disturbances in the water
      status, as was reported for some plants exposed to heavy metals. However, to our
      knowledge, these mechanisms have not been studied in depth in soybean plants
      exposed to As. The aim of the present work was to analyze possible changes in
      water relations and the responses developed in soybean plants under arsenate
      (AsV) and arsenite (AsIII) stress. We discuss physiological and morphological
      aspects of the As stress response, such as root absorption rate, water content,
      stomatal conductance, water and osmotic potential, accumulation of compatible
      solutes, leaf conducting tissues and stomata characteristics. AsV and AsIII
      caused a significant decrease in root absorption rate, which could reduce
      metalloid uptake. On the other hand, water content decreased at the beginning of
      the treatment but was re-established after 4 and 8 d. This was correlated with a
      decrease in stomatal conductance and a reduction in leaf water and osmotic
      potential due to the accumulation of proline and soluble sugars. Besides, smaller
      leaf xylem vessels and abnormal stomata were observed in plants under As
      treatment. These mechanisms increased the plant's ability to retain water and
      therefore to avoid dehydration. Thus, the results of the present work contribute
      to the understanding of how soybean responds to As, by describing key tolerance
      strategies to the metalloid.

PMID- 29220740
TI  - Validity of health insurance data to identify people with epilepsy.
AB  - BACKGROUND: Large administrative databases may prove useful to assess epilepsy
      related comorbidity and mortality. Despite their increased use, their validity as
      data source in epilepsy is yet under-ascertained. METHODS: Achmea is a large
      Dutch health insurance company covering about 25% of the population. We performed
      a retrospective cohort study using data from the Achmea Health Insurance Database
      (AHID) over the period 2006-2009. To assess the validity of epilepsy codes in the
      AHID, we randomly invited 1000 individuals (age 18-75 years insured by Achmea),
      attending an epilepsy centre or a district hospital during 2006-2009, to
      participate. Informed consent was provided and 293 were eligible for inclusion.
      We compared the diagnostic codes for epilepsy in AHID with the diagnosis in their
      case-notes (reference standard). As additional measure of validity, we compared
      prevalence of epilepsy codes in AHID (based on anonymized data of all 26.297
      subjects with this code in AHID) with epilepsy prevalence rates in the general
      Dutch population to estimate an age-specific standardized prevalence ratio.
      RESULTS: We identified 293 participants with an epilepsy code in AHID. The
      majority (278) of them had a definite or possible diagnosis of epilepsy in the
      case-notes; i.e. a positive predictive value of 0.95 (95% CI 0.92-0.97). The
      overall prevalence of epilepsy codes in the AHID was slightly higher than the
      putative prevalence in the general Dutch population (7.4/1.000 vs. 6.8/1.000)
      with a Standardized Prevalence Ratio of 1.08 (95% CI: 1.08-1.09). CONCLUSIONS:
      Our findings demonstrate the validity of AHID data for a diagnosis of epilepsy
      and confirm previous work on using administrative data for epilepsy research.

PMID- 29220738
TI  - Increasing value and reducing waste by optimizing the development of complex
      interventions: Enriching the development phase of the Medical Research Council
      (MRC) Framework.
AB  - BACKGROUND: In recent years there has been much emphasis on 'research waste'
      caused by poor question selection, insufficient attention to previous research
      results, and avoidable weakness in research design, conduct and analysis. Little
      attention has been paid to the effect of inadequate development of interventions
      before proceeding to a full clinical trial. OBJECTIVE: We therefore propose to
      enrich the development phase of the MRC Framework by adding crucial elements to
      improve the likelihood of success and enhance the fit with clinical practice
      METHODS: Based on existing intervention development guidance and synthesis, a
      comprehensive iterative intervention development approach is proposed. Examples
      from published reports are presented to illustrate the methodology that can be
      applied within each element to enhance the intervention design. RESULTS: A
      comprehensive iterative approach is presented by combining the elements of the
      MRC Framework development phase with essential elements from existing guidance
      including: problem identification, the systematic identification of evidence,
      identification or development of theory, determination of needs, the examination
      of current practice and context, modelling the process and expected outcomes
      leading to final element: the intervention design. All elements are drawn from
      existing models to provide intervention developers with a greater chance of
      producing an intervention that is well adopted, effective and fitted to the
      context. CONCLUSION: This comprehensive approach of developing interventions will
      strengthen the internal and external validity, minimize research waste and add
      value to health care research. In complex interventions in health care research,
      flaws in the development process immediately impact the chances of success.
      Knowledge regarding the causal mechanisms and interactions within the intended
      clinical context is needed to develop interventions that fit daily practice and
      are beneficial for the end-user.

PMID- 29220741
TI  - An update on the prevalence and incidence of epilepsy among older adults.
AB  - OBJECTIVE: To estimate the prevalence and incidence of epilepsy among
      beneficiaries of Arizona Medicare aged 65 and over. METHODS: An analysis of
      Medicare administrative claims data for 2009-2011 for the State of Arizona was
      conducted. Epilepsy was defined as a beneficiary who had either>=one claim with
      diagnostic code of 345.xx (epilepsy) or at least two claims with diagnosis code
      of 780.3x (seizure) >=30days apart. Stroke-related and psychiatric comorbidities
      were determined by diagnostic codes. Average annual prevalence and incidence were
      calculated and stratified by demographic characteristics and comorbidities. Odds
      ratios (OR) and 95% confidence intervals (CI) were calculated as measures of
      effect for prevalence and incidence and the chi-square statistic was calculated
      to compare the proportions of epilepsy cases with and without comorbidities
      (alpha=0.05). RESULTS: The overall average annual prevalence and incidence over
      the study period was 15.2/1000 and 6.1/1000, respectively. Relative to the 65-69
      age group and White beneficiaries, the highest prevalence was observed for
      beneficiaries 85 years or older (19.8/1000, OR 1.66, 95% CI 1.53-1.81) and Native
      Americans (21.2/1000, OR 1.42, 95% CI 1.25-1.62). In contrast, the highest
      incidence rates were observed for beneficiaries 85 years and older (8.5/1000, OR
      1.82, 95% CI 1.60-2.07) and for Black beneficiaries (8.7/1000, OR 1.44, 95% CI
      1.12-1.86). The incidence rate for Native Americans was not significantly
      different from that for White beneficiaries (6.2/1000, OR 1.02, 95% CI 0.81
      1.29). More than one quarter of all cases (25.7%) and 31% of incident cases had
      either stroke-related and/or psychiatric comorbidities (all p-values < 0.001).
      CONCLUSIONS: Epilepsy is a significant neurological disease among Medicare
      beneficiaries 65 years and older. Beneficiaries aged 85 and older and Black and
      Native Americans experienced higher rates of epilepsy than other demographic
      subgroups compared to White beneficiaries.

PMID- 29220742
TI  - Meta-analyses of newer antiepileptic drugs as adjunct for treatment of focal
      epilepsy in children.
AB  - AIM: This study conducted a systematic review evaluating the effectiveness of
      newer antiepileptic drugs (AEDs) (namely, lamotrigine, levetiracetam, topiramate,
      vigabatrin, zonisamide, oxcarbazepine, perampanel, gabapentin, and stiripentol)
      as add-on for treatment of focal epilepsy in children. METHODS: Articles were
      retrieved from EMBASE, Medline and Cochrane Library from inception to January
      2016. Treatment outcomes were analysed based on responder, seizure-free,
      withdrawal and adverse event rates. Quality of each study was also assessed.
      RESULTS: Twelve articles fulfilled the inclusion criteria. Heterogeneity and
      quality of the included studies were considered acceptable. Overall, newer AEDs
      as adjunct therapy in children with inadequate control of focal seizure showed a
      trend of better seizure outcomes. The pooled ORs for responder, seizure-free and
      withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69
      (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively
      higher than placebo (OR:1.64, 95%CI:1.13, 2.39). CONCLUSION: In our updated
      review, newer AEDs as adjunct therapy for focal epilepsy in children have trends
      of better effectiveness compared to placebo. Newer AEDs are associated with
      statistically more children with >50% seizure reduction, and a trend of better
      seizure freedom. Their tolerability would also be considered acceptable with the
      observed low withdrawal rate. However, the relative lack of well-conducted RCTs
      evaluating their effectiveness against other active AED treatment in children
      would not facilitate evidence-based practice. This highlights the knowledge gap
      and the need for more well-conducted RCTs against active treatments to ascertain
      the long term effectiveness and the role of newer AEDs in managing epilepsy in
      children.

PMID- 29220733
TI  - A fast method for GHB-GLUC quantitation in whole blood by GC-MS/MS (TQD) for
      forensic purposes.
AB  - gamma-Hydroxybutyric acid (GHB) is an endogenous compound with a historical use,
      both in licit and illicit terms. Importantly, the post-mortem behavior of GHB has
      been studied due to the possibility of using this compound as a biomarker for
      estimating the post-mortem interval (PMI). However, the post-mortem behavior of
      the recently discovered glucuronated GHB metabolite (GHB-GLUC) has not been
      studied. Nevertheless, GHB-GLUC may also have potential both to assist in PMI
      determination and also to increase the window of detection of GHB consumption. In
      this work, for the first time, a reliable method using GC-MS/MS for the
      quantification of GHB-GLUC in whole blood samples was developed and validated,
      with a simple, fast and cheap sample pretreatment. The method proved to be
      specific, precise, linear in a work range between 200 and 5000ng/mL, with LOD and
      LOQ of 52.65ng/mL and 200ng/mL, respectively, and an extraction recovery of 51%.
      Furthermore, the method was applied to a set of real post-mortem blood samples
      non-related with GHB intoxication and the obtained results were also discussed.

PMID- 29220743
TI  - The Cigarette Dependence Scale and Heaviness of Smoking Index as predictors of
      smoking cessation after 10weeks of nicotine replacement therapy and at 6-month
      follow-up.
AB  - INTRODUCTION: The reliability and validity of the Cigarette Dependence Scale
      (CDS) has been tested in online studies and compared with other tobacco
      dependence measures. Findings regarding its ability to predict smoking cessation
      have been mixed. We examined whether the CDS predicted cessation among a sample
      that received nicotine replacement therapy (NRT) at a community workshop and
      assessed the incremental predictive validity of the CDS-5 and CDS-12 over the 2
      item Heaviness of Smoking Index (HSI). METHODS: Individuals 18 or older, smoking
      at least 10 cigarettes daily and intending to quit within 30days received 10weeks
      of NRT at a smoking cessation workshop. A total of 2661 individuals attended
      workshops throughout Ontario, Canada from 2007 to 2008 and completed the CDS and
      HSI at baseline. Follow-up surveys were conducted at end of treatment and 6months
      post-treatment. Smoking cessation outcome was 7-day point prevalence abstinence.
      RESULTS: The CDS-5, CDS-12 and HSI total scores predicted abstinence at end-of
      treatment and 6-month follow-up. The HSI was a slightly better predictor of
      abstinence according to pseudo-R2 and area under the receiver operating
      characteristic curve (AUC) values. In hierarchical regression analyses, both HSI
      items were independent predictors of cessation. Only one additional CDS item was
      a significant independent predictor of cessation at end of treatment, though
      higher scores were associated with greater odds of abstinence. CONCLUSION: The
      HSI had similar or marginally better predictive ability with respect to quit
      outcome compared to the CDS-5 and CDS-12 in a sample motivated to make a quit
      attempt using NRT.

PMID- 29220744
TI  - Sensitive detection of pyoverdine with an electrochemical sensor based on
      electrochemically generated graphene functionalized with gold nanoparticles.
AB  - The design and development of an electrochemical sensor for the sensitive and
      selective determination of pyoverdine, a virulence factor secreted by Pseudomonas
      aeruginosa, bacteria involved in nosocomial infections is presented in this work.
      The presence of pyoverdine in water and body fluids samples can be directly
      linked to the presence of the Pseudomonas bacteria, thus being a nontoxic and low
      cost marker for the detection of water pollution as well as for the biological
      contamination of other media. The sensor was elaborated using layer-by-layer
      technique for the deposition of a graphene-gold nanoparticles composite film on
      the graphite-based screen printed electrode, from aqueous suspension. Under
      optimal conditions, the electrochemical signal corresponding to the pyoverdine
      oxidation process was proportional to its concentration, showing a wide linear
      range from 1 to 100MUmolL-1 and a detection limit of 0.33MUmolL-1. This sensor
      discriminate with satisfactory recoveries the target analyte in different real
      matrices and also exhibited low response to other interfering species, proving
      that this technique is promising for medical and environmental applications. In
      addition, the proposed nanocomposite platform presented good reproducibility,
      high and long term stability, the sensitivity for pyoverdine remain unchanged
      after being stored at 4 degrees C for four weeks.

PMID- 29220734
TI  - High throughput routine determination of 17 tyrosine kinase inhibitors by LC
      MS/MS.
AB  - Several studies have shown that therapeutic drug monitoring of tyrosine kinase
      inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been
      developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in
      human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib,
      erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib,
      regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib).
      Drugs were arranged in four groups, according to their plasma concentration
      range: 0.1-200ng/ml, 1-200ng/ml, 4-800ng/ml and 25-5000ng/ml. Solid phase
      extraction was used and separation was performed with HPLC using a gradient
      system on a solid core particle C18 column (5*2.1mm, 1.6MUm). Ions were detected
      with a triple quadrupole mass spectrometry system. This assay allows rapid
      determination of 19 TKI in less than 5min per run. This high throughput routine
      method will be useful to adjust doses of oral anticancer drugs in order to
      improve treatments efficacy.

PMID- 29220746
TI  - Testing bidirectional relationships between alcohol use and depressive symptoms:
      What is the role of the serotonin transporter gene?
AB  - Alcohol abuse often co-exists with a major depressive disorder. In order to
      understand the development of this comorbidity, it is important to concentrate on
      the preceding process. It has been suggested that the link between alcohol use
      and depressive symptoms is a result of an interaction with genetic factors. The
      aim of this study was to longitudinally examine the effect of the 5-HTTLPR
      genotype on the association between depressive symptoms and alcohol use in a
      Dutch community sample. Following a stepwise approach, bivariate correlations,
      longitudinal regression analyses, and latent growth curve analyses were
      separately conducted for 316 males and 321 females. A positive correlation
      between depressive symptoms and alcohol use was shown in female carriers of the 5
      HTTLPR short allele. In addition, latent growth curve analyses showed a positive
      association between alcohol use and the intercept of depressive symptoms (but not
      the slope), but only in female carriers of the 5-HTTLPR short allele. These
      findings show that alcohol use may be positively related, at least cross
      sectionally, to depressive symptoms in female carriers of the 5-HTTLPR S allele,
      and indicate that moderators such as SLC6A4 genotype and sex need to be taken
      into account when examining associations between depressive symptoms and drinking
      behavior. In order to gain insight into the longitudinal association between
      alcohol use and depressive symptoms, studies should concentrate on earlier stages
      and focus on more fine-grained research designs that allow day-to-day changes in
      both alcohol use and depressive symptoms.

PMID- 29220750
TI  - Differential sensitivity of light-harnessing photosynthetic events in wheat and
      sunflower to exogenously applied ionic and nanoparticulate silver.
AB  - Potential impacts of inevitable leaks of silver nanoparticles (AgNPs) into
      environment on human beings need attention. Owing to the vitality of
      photosynthesis in maintaining life and ecosystem functioning, impacts of
      exogenously applied nanoparticulate and Ag+ on photosystem (PS)II function, which
      governs overall photosynthesis, in wheat and sunflower were evaluated. PSII
      efficiency and related Chl a fluorescence kinetics of these two plants remained
      unaffected by AgNPs. However, Ag+ caused a significant decline in the PSII
      activity and related fluorescence steps in wheat, but not in sunflower. Electron
      flow between QA and PQ pool was found most sensitive to Ag+. Number of active
      reaction centers, electron transport, trapping of absorbed light for
      photochemistry, and performance index declined, while dissipation of absorbed
      light energy as heat significantly increased in wheat exposed to Ag+. Total
      antioxidant activity in sunflower was least affected by both Ag and AgNPs. In
      contrast, in the case of wheat, the antioxidant activity was declined by Ag+ but
      not by AgNPs. Further, the amount of silver absorbed by plants exposed to Ag+ was
      higher than that absorbed by plants exposed to AgNPs. While wheat retained
      majority of Ag in its roots, sunflower showed major Ag accumulation in stem.
      Photosynthetic events in sunflower, unlike wheat, were least affected as no
      detectable Ag levels was recorded in their leaves. Our findings revealed that
      AgNPs seemed non/less-toxic to light harnessing photosynthetic machinery of
      wheat, compared to Ag+. Photosynthetic events in sunflower were not affected by
      Ag+, either, as its translocation to leaves was restricted.

PMID- 29220747
TI  - Effects of group II metabotropic glutamate receptor modulation on ethanol- and
      sucrose-seeking and consumption in the rat.
AB  - Previous studies suggest that group II metabotropic glutamate receptors
      (mGluR2/3) are involved in regulating ethanol-seeking and consumption. The
      mGluR2/3 agonist LY379268 (LY37) and selective mGluR2 positive allosteric
      modulator biphenyl-indanone A (BINA) were used to investigate the relative
      contribution of mGlu2 and mGlu3 receptors on ethanol- and sucrose-seeking and
      consumption. A microinjection study was then performed to examine the role of
      nucleus accumbens (NAc) core mGluR2/3 on ethanol-seeking. For the systemic
      experiments, separate groups of male Wistar rats [LY37 (0-2.0 mg/kg); BINA (0-20
      mg/kg)] were trained to complete a response requirement (RR) resulting in access
      to 10% ethanol or 2% sucrose (in separate groups) for a 20-min drinking period.
      Animals then underwent consummatory testing (weekly drug injections with RR1)
      followed by appetitive testing (weekly drug injections followed by extinction
      session). A separate group of male Wistar rats was surgically implanted with
      bilateral guide cannulae directed toward the NAc core and had weekly
      microinjections followed by an extinction session. Systemic administration of the
      mGluR2/3 agonist LY37 significantly reduced ethanol- and sucrose-seeking. The
      same treatment also reduced sucrose consumption and body weight (24-h post
      injection). Systemic administration of the selective mGluR2 PAM BINA, however,
      had no effect on either seeking or consumption of ethanol or sucrose. Intra
      accumbens core LY37 significantly reduced ethanol-seeking. These findings suggest
      that systemic mGluR2/3 agonism, but not allosteric modulation of mGluR2, reduces
      reinforcer-seeking. In particular, NAc core group II mGluR may be involved in
      regulating ethanol-seeking.

PMID- 29220749
TI  - Phosphorus-loaded biochar changes soil heavy metals availability and uptake
      potential of maize (Zea mays L.) plants.
AB  - Biochar (BC) was produced by pyrolyzing the date palm leaf waste at 600  degrees
      C and then loaded with phosphorus (P) via sorption process. Greenhouse pot
      experiment was conducted to investigate the application effects of BC and P
      loaded biochar (BCP) on growth and availability of P and heavy metals to maize
      (Zea mays L.) plants grown in contaminated mining soil. The treatments consisted
      of BC and BCP (at application rates of 5, 10, 20, and 30 g kg-1 of soil),
      recommended NK and NPK, and a control (no amendment). Sorption experiment showed
      that Langmuir predicted maximum P sorption capacity of BC was 13.71 mg g-1.
      Applying BCP increased the soil available P, while BC and BCP significantly
      decreased the soil labile heavy metals compared to control. Likewise, heavy
      metals in exchangeable and reducible fractions were transformed to more stable
      fraction with BC and BCP applications. The highest application rate of BCP (3%)
      was most effective treatment in enhancing plant growth parameters (shoot and root
      lengths and dry matter) and uptake of P and heavy metals by 2-3 folds. However,
      based on metal uptake and phytoextraction indices, total heavy metals extraction
      by maize plants was very small for practical application. It could be concluded
      that using P-loaded biochar as a soil additive may be considered a promising tool
      to immobilize heavy metals in contaminated mining areas, while positive effects
      on the biomass growth of plants may assist the stabilization of contaminated
      areas affected by wind and water erosion.

PMID- 29220754
TI  - Association of high mortality with extended-spectrum beta-lactamase (ESBL)
      positive cultures in community acquired infections.
AB  - PURPOSE: Infections due to multidrug resistant organisms have become a serious
      health concern worldwide. The present study was conducted to investigate the
      spectrum of microbial resistance pattern in the community and their effects on
      mortality. METHODS: A retrospective review and analysis of prospectively
      collected data was done of all patients admitted with diagnosis of sepsis in two
      tertiary care ICU's for a period of two years. Demographics, culture positivity,
      microbial spectrum, resistance pattern and outcome data were collected. RESULTS:
      Out of 5309 patients enrolled; 3822 had suspected clinical infection on admission
      with 1452 patients growing positive microbial cultures. Among these, 201
      bacterial strains were isolated from patients who had community acquired
      infections. 73% were Gram negative bacilli, commonest being E. coli (63%). 63.4%
      E. coli and 60.7% Klebsiella isolates were ESBL producers. The mortality in ESBL
      positive infections was significantly higher as compared to ESBL negative
      infections (Odds ratio 2.756). Moreover, ESBL positive patients empirically
      treated with Beta Lactams+Beta Lactamase inhibitors (BL+BLI) had significantly
      higher mortality as compared to patients treated with carbapenems. More data from
      multiple centres need to be gathered to formulate appropriate antibiotic policy
      for critically ill patients admitted from the community.

PMID- 29220752
TI  - Genomic characterization of the porcine CRTC3 and the effects of a non-synonymous
      mutation p.V515F on lean meat production and belly fat.
AB  - cAMP-responsive element-binding protein (CREB)-regulated transcriptional
      coactivator 3 (CRTC3) is well known to be related to obesity in humans and mice.
      However, the effects of CRTC3 have not been studied in pigs. Here, we
      characterized the structure of the porcine CRTC3 gene and identified single
      nucleotide polymorphisms (SNPs) in its coding region. Moreover, mRNA expression
      profiles of CRTC3 in muscle and fat tissues were examined. Of the 40 identified
      SNPs, the p.V515F mutation, located on exon 16, was genotyped in 368 Yorkshire
      pigs. The p.V515F mutation was significantly associated with lean meat production
      ability, including reduced back fat thickness (P=0.0317) and loin eye area
      (P=0.0174). Moreover, the SNP was significantly associated with differences in
      intermuscular fat (P=0.0092), total muscle area in the belly (P=0.0108), and
      total fat percentage in the belly (P=0.0298). Taken together, our results suggest
      that the p.V515F mutation affects to lean meat production ability and amount of
      belly fat.

PMID- 29220751
TI  - Photolysis of highly brominated flame retardants leads to time-dependent dioxin
      responsive mRNA expression in chicken embryonic hepatocytes.
AB  - Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) and 2,2',3,3',4,4',5,5',6,6'
      decabromodiphenyl ether (BDE-209) are flame retardant chemicals that can undergo
      photolytic degradation. The present study compared the time-dependent photolyic
      degradation of TeDB-DiPhOBz and BDE-209, and dioxin-like product formation as a
      result of (UV) irradiation (I; irradiation time periods of 0, 1, 4, 15 and 40
      days). Photo-degraded product fractions of UV-I-TeDB-DiPhOBz (nominal
      concentration: 1.9 MUM) were administered to chicken embryonic hepatocytes (CEH),
      and significant induction of CYP1A4/5 mRNA expression was observed for fractions
      collected at the day 15 and 40 time points (fold change of 7.3/3.6 and 9.1/4.7,
      respectively). For the UV-I-BDE-209 fractions (nominal concentration: 10 MUM),
      significant CYP1A4/5 up-regulation occurred at all time points, and the fraction
      collected on day 1 induced the greatest fold change of 510/86, followed by 410/68
      (day 4) and 110/26 (day 15), respectively. For the UV-I-BDE-209 fraction
      collected at day 40, significant CEH cytotoxicity was observed. As a result,
      CYP1A4/5 expression was determined at a nominal concentration of 1 MUM instead of
      10 MUM and CYP1A4/5 fold changes of 11/8.2 (day 40) were observed. Fractions
      eliciting the greatest CYP1A4/5 mRNA upregulation were further screened for
      transcriptomic effects using a PCR array comprising 27 dioxin-responsive genes. A
      total of 6 and 16 of the 27 target genes were up or down-regulated following UV-I
      TeDB-DiPhOBz and UV-I-BDE-209 exposure, respectively. Overall, and regardless of
      the formation rate, these results raise concerns regarding the potential
      formation of dioxin-like compounds from flame retardants in products and
      materials such as plastics, and in natural sunlight irradiation situations in the
      environment (e.g. in landfill sites or electronic waste facilities).

PMID- 29220755
TI  - Coronary artery calcification predicts cardiovascular complications after sepsis.
AB  - PURPOSE: Sepsis is a highly prevalent and fatal condition, with reported
      cardiovascular event rates as high as 25-30% at 1year. Risk stratification in
      septic patients has been extremely limited. MATERIAL AND METHODS: 267 septic
      patients with detectable troponin levels, APACHE II scores, and CT scans of the
      chest or abdomen were assessed. Patients with a recent cardiac intervention were
      excluded. Coronary artery calcification (CAC) was identified as present or absent
      on body CT scans. Cardiovascular death, acute myocardial infarction (AMI), or PCI
      at 1year was assessed using multivariate logistic regression analysis. RESULTS:
      Patients with CAC were older, predominantly male with more risk factors for
      coronary disease, but similar peak troponin levels and APACHE II scores. In a
      multivariate analysis, CAC was predictive of the primary outcome (OR 6.827; 95%
      CI 1.336-54.686; p=0.037). Patients with no CAC, history of CHF or CKD were at
      low risk (<1%) for cardiovascular complications at 1year even at very high
      troponin levels (<8.0ng/dL). CONCLUSION: CAC risk stratifies septic patients for
      cardiovascular complications better than traditional risk factors and can be
      identified on body CT scans. This novel, risk stratifying framework built on CAC
      can help guide individualized management of septic patients.

PMID- 29220753
TI  - A systematic review of the gait characteristics associated with Cerebellar
      Ataxia.
AB  - BACKGROUND: Cerebellar Ataxias are a group of gait disorders resulting from
      dysfunction of the cerebellum, commonly characterised by slowly progressing
      incoordination that manifests as problems with balance and walking leading to
      considerable disability. There is increasing acceptance of gait analysis
      techniques to quantify subtle gait characteristics that are unmeasurable by
      current clinical methods This systematic review aims to identify the gait
      characteristics able to differentiate between Cerebellar Ataxia and healthy
      controls. METHODS: Following systematic search and critical appraisal of the
      literature, gait data relating to preferred paced walking in Cerebellar Ataxia
      was extracted from 21 studies. A random-effect model meta-analysis was performed
      for 14 spatiotemporal parameters. Quality assessment was completed to detect risk
      of bias. RESULTS: There is strong evidence that compared with healthy controls,
      Cerebellar Ataxia patients walk with a reduced walking speed and cadence, reduced
      step length, stride length, and swing phase, increased walking base width, stride
      time, step time, stance phase and double limb support phase with increased
      variability of step length, stride length, and stride time. CONCLUSION: The
      consensus description provided here, clarifies the gait pattern associated with
      ataxic gait disturbance in a large cohort of participants. High quality research
      and reporting is needed to explore specific genetic diagnoses and identify
      biomarkers for disease progression in order to develop well-evidenced clinical
      guidelines and interventions for Cerebellar Ataxia.

PMID- 29220756
TI  - The impact of sustained new-onset atrial fibrillation on mortality and stroke
      incidence in critically ill patients: A retrospective cohort study.
AB  - PURPOSE: The purpose of the study is to evaluate the impact of sustained new
      onset AF on mortality and the incidence of stroke in critically ill non-cardiac
      surgery patients. MATERIAL AND METHODS: This was a retrospective cohort study of
      non-cardiac surgery patients with new-onset AF conducted in a general intensive
      care unit. We compared patients remaining in AF with those restored to sinus
      rhythm (SR) at 6h after the onset of AF and conducted multivariable logistic
      regression analysis for in-hospital mortality. We also examined the impact of the
      cumulative time of AF duration in the first 48h on hospital outcomes. RESULTS:
      New-onset AF occurred in 151 of 1718 patients (9%). Patients with sustained AF
      after 6h (34% of 151 patients included) experienced greater in-hospital mortality
      than patients with SR at 6h (37% vs. 20%, p=0.033). Multivariable logistic
      regression analysis confirmed the association between AF at 6h and in-hospital
      mortality (adjusted odds ratio, 3.14; 95% confidence intervals, 1.28-7.69;
      p=0.012). Patients with longer AF duration had greater in-hospital mortality
      (p=0.043) and in-hospital ischemic stroke incidence (p=0.041). CONCLUSION:
      Sustained new-onset AF is associated with poor outcomes.

PMID- 29220758
TI  - Interaction of a digestive protease, Candida rugosa lipase, with three
      surfactants investigated by spectroscopy, molecular docking and enzyme activity
      assay.
AB  - The extensive use of surfactants in food, laundry products and agriculture has
      caused concern about their biosafety. However, few studies have been done on
      their potential effect on the lipase which has always been used with surfactants
      in food and laundry industry. Herein, we investigated the interaction of three
      surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate
      (SDBS), sodium lauryl sulfonate (SLS)) with Candida rugosa lipase (CRL), which is
      a popular biocatalyst used regularly with surfactants. The effect of the three
      surfactants on the conformation and activity of CRL was evaluated by using
      multiple spectral methods, enzyme activity assay and molecular docking modeling.
      The results demonstrated that CRL interacted with SDS, SDBS and SLS primarily
      through hydrophobic forces, H-bonding and electrostatic forces, respectively. The
      binding constants (KA) of SDBS with CRL varied with temperature: 1.99*103mol/L at
      298K and 4.13*103mol/L at 318K. SDS and SDBS affected the secondary structure and
      skeleton of CRL, which changed the polarity of CRL and enhanced its activity. SLS
      also changed the secondary structure and activity of CRL moderately, but had
      little effect on its polarity and chromophore microenvironment. Accordingly, all
      three surfactants exhibited effect to CRL on the molecular level calling for more
      attention to pay on their biosafety. The work demonstrates that SDS, SDBS and SLS
      could cause negative effects to CRL from different angles and therefore are not
      bio-friendly detergents.

PMID- 29220757
TI  - Association between postoperative fluid balance and acute kidney injury in
      patients after cardiac surgery: A retrospective cohort study.
AB  - PURPOSE: The present study aims to explore appropriate postoperative fluid
      management in patients after cardiac surgery. MATERIALS AND METHODS: Data were
      extracted from an online database. Associations between fluid balance (FB), fluid
      intake and mortality were investigated. RESULTS: Compared to zero FB (level 3),
      more negative FB (level 1, odds ratio (OR): 0.938, 95% CI: 0.631-1.394; level 2,
      OR: 0.921, 95% CI: 0.709-1.196) could not further decrease AKI incidence while
      positive FB was associated with higher AKI incidence (level 4, OR: 1.272, 95% CI:
      1.028-1.573; level 5, OR: 2.042, 95% CI: 1.652-2.524). Both limited (level 1, OR:
      1.354, 95% CI: 1.065-1.699) and increased postoperative fluid intake (level 3,
      OR: 1.127, 95% CI: 0.890-1.430; to level 5, OR: 1.405, 95% CI: 1.105-1.786) were
      associated with increased AKI incidence, compared to level 2. Multivariable
      logistic models using linear spline function showed a similar pattern.
      CONCLUSIONS: Compared to zero FB, postoperative positive FB was associated with
      higher AKI incidence. Yet, the association between negative FB and AKI was
      insignificant. A "U"-shape association between postoperative fluid intake and AKI
      was detected.

PMID- 29220760
TI  - Historical trace element accumulation in marine sediments from the Tamaulipas
      shelf, Gulf of Mexico: An assessment of natural vs anthropogenic inputs.
AB  - : The Gulf of Mexico is considered one of the world's major marine ecosystems,
      supporting important fisheries and habitats such as barrier islands, mangrove
      forests, seagrass beds, coral reefs etc. It also hosts a range of complex
      offshore petroleum exploration, extraction, and refining industries, which may
      have chronic or acute impacts on ecosystem functioning. Previous work on the
      marine effects of this activity is geographically incomplete, and has tended to
      focus on direct hydrocarbon impacts, while impacts from other related
      contaminants (e.g. heavy metals, salt-rich drilling muds) which may be discharged
      from oil facilities have not been widely assessed. Here, we examine historical
      trace element accumulation in marine sediments collected from four sites in the
      Tamaulipas shelf, Gulf of Mexico, in the area of the Arenque oil field. Dated
      sediment cores were used to examine the sources, and historical and contemporary
      inputs, of trace metals (including those typically present in oil industry
      discharges) and their potential biological impact in the Tamaulipas aquatic
      environment over the last 100years. CaO (i.e. biogenic component) normalized data
      showed increasing V, Cr, Zn, Cu, Pb, Zr and Ba towards the sediment surface in
      three of the four cores, with Ba and V (based on an adverse effect index)
      possibly associated with adverse effects on organisms. Dated Ba/CaO profiles show
      an increase of 30-137% after opening of oil installations in the study area, and
      can be broadly correlated with increasing oil industry activities across the
      wider Gulf of Mexico. Data do not record however a clear enhancement of Ba
      concentration in sediment cores collected near to oil platforms over more distal
      cores, indicating that any Ba released from drilling platforms is incorporated
      quickly into the sediments around the drilling sites, and once this element has
      been deposited its rate of resuspension and mobility is low. CAPSULE ABSTRACT:
      Sediment core data from the Tamaulipas shelf show the influence of oil industry
      activities on selected trace element concentrations, with Ba/CaO broadly
      correlating with increasing oil industry activities across the wider Gulf of
      Mexico.

PMID- 29220748
TI  - Assisted phytostabilization of a multicontaminated mine technosol using biochar
      amendment: Early stage evaluation of biochar feedstock and particle size effects
      on As and Pb accumulation of two Salicaceae species (Salix viminalis and Populus
      euramericana).
AB  - Soil contamination by metal(loid)s is one of the most important environmental
      problem. It leads to loss of environment biodiversity and soil functions and can
      have harmful effects on human health. Therefore, contaminated soils could be
      remediated, using phytoremediation. Indeed, plant growth will improve soil
      conditions while accumulating metal(loid)s and modifying their mobility. However,
      due to the poor fertility and high metal(loid)s levels of these soils,
      amendments, like biochar, has to be applied. This study was performed on a former
      mine technosol contaminated by As and Pb and aimed to study (i) the effect of
      biochar on soil physico-chemical properties and plant phytostabilization
      potential (ii) biochar feedstock and particle size effects. In this goal, a
      mesocosm experiment was set up using four different biochars, obtained from two
      feedstocks (lightwood and pinewood) and harboring two particle sizes (inf. 0.1 mm
      and 0.2-0.4 mm) and two Salicaceae species. Soil and soil pore water physico
      chemical properties as well as plant growth and metal(loid)s distribution were
      assessed. The results showed that biochar was efficient in improving soil physico
      chemical properties and reducing Pb soil pore water concentrations. This
      amelioration allowed plant growth and increased dry weight production of both
      species. Regarding metal(loid)s distribution, willow and poplar showed an As and
      Pb accumulation in roots and low translocation towards edible parts, i.e stems
      and leaves, which shows a phytostabilization potential. Finally, the 2 biochar
      parameters, feedstock and particle size, only affected soil and soil pore water
      physico-chemical properties while having no effect on plant growth.

PMID- 29220759
TI  - Polymer inclusion membrane to access Zn speciation: Comparison with root uptake.
AB  - Metal speciation studies can be performed with a new technique based on a
      functionalized membrane. The estimation of not only the total amount of metal,
      but also the metal available to living organisms is very important. In this
      context, we have investigated the use of a polymer inclusion membrane (PIM) in a
      new tool for the determination of free metal ion concentration. In order to check
      the usefulness of PIM devices in metal speciation studies and metal availability
      to potato plants (Solanum tuberosum), Zn has been chosen as a case study. The PIM
      designed for Zn transport uses polyvinyl chloride (PVC) as polymer and di-(2
      ethylhexyl) phosphoric acid (D2EHPA) as carrier, with 0.01M nitric acid in the
      receiving solution. The stability of the PIM has been demonstrated and good
      linearity of PIM-device fluxes (JPIM) with free metal concentration was observed
      for total metal concentrations ranging from 3MUM up to 70MUM. The presence of
      different ligands, such as ethylenediaminetetraacetic acid (EDTA), humic acid
      (HA) and citrate, greatly influences the measured JPIM because the formation of
      metal complexes in the donor phase decreases the free Zn concentration in the
      sample. Good correlation has been found when comparing PIM fluxes and metal
      accumulation in potato plants roots in the presence of EDTA. But, the root uptake
      did not change when adding citrate and HA to the hydroponic medium, so the uptake
      does not always follows the Free Ion Activity Model (FIAM). These ligands might
      induce physiological changes in the roots and enhance metal uptake.

PMID- 29220745
TI  - Identification and characterization of six peroxiredoxin transcripts from mud
      crab Scylla paramamosain: The first evidence of peroxiredoxin gene family in
      crustacean and their expression profiles under biotic and abiotic stresses.
AB  - The peroxiredoxins (Prxs) define a novel and evolutionarily conserved superfamily
      of peroxidases able to protect cells from oxidative damage by catalyzing the
      reduction of a wide range of cellular peroxides. Prxs have been identified in
      prokaryotes as well as in eukaryotes, however, the composition and number of Prxs
      family members vary in different species. In this study, six Prxs were firstly
      identified from the mud crab Scylla paramamosain by RT-PCR and RACE methods. Six
      SpPrxs can be subdivided into three classes: (a) three typical 2-Cys enzymes
      denominated as Prx1/2, 3, 4, (b) two atypical 2-Cys enzymes known as Prx5-1 and
      Prx5-2, and (c) a 1-Cys isoform named Prx6. The evolutionarily conserved
      signatures of peroxiredoxin catalytic center were identified in all six SpPrxs.
      Phylogenetic analysis revealed that SpPrx3, SpPrx4, SpPrx5s and SpPrx6 were
      clearly classified into Prx3-6 subclasses, respectively. Although SpPrx1/2 could
      not be grouped into any known Prx subclasses, SpPrx1/2 clustered together with
      other arthropods Prx1 or unclassified Prx and could be classified into the
      typical 2-Cys class. The comparative and evolutionary analysis of the Prx gene
      family in invertebrates and vertebrates were also conducted for the first time.
      Tissue-specific expression analysis revealed that these six SpPrxs were expressed
      in different transcription patterns while the highest expression levels were
      almost all in the hepatopancreas. Quantitative RT-PCR analysis exhibited that the
      gene expression profiles of six SpPrxs were distinct when crabs suffered biotic
      and abiotic stresses including the exposures of Vibrio alginolyticus, poly (I:C),
      cadmium and hypoosmotic salinity, suggesting that the SpPrxs might play different
      roles in response to various stresses. The recombinant proteins including the
      SpPrx1/2, SpPrx4, SpPrx5-1 and SpPrx6 were purified and the peroxidase activity
      assays indicated that all these proteins can reduce H2O2 in a typical DTT
      dependent manner. To our knowledge, this is the first study about the
      comprehensive characterization of Prx gene family in Scylla paramamosain and even
      in crustaceans. These results would broaden the current knowledge of the whole
      Prx family as well as be helpful to understand and clarify the evolutionary
      pattern of Prx family in invertebrate and vertebrate taxa.

PMID- 29220761
TI  - Climate-change potential effects on the hydrological regime of freshwater springs
      in the Italian Northern Apennines.
AB  - In large areas of the Italian Northern Apennines, hundreds of low-yield springs
      provide water for drinking and industrial purposes, with short groundwater flow
      paths being formed within fractured sedimentary rock units. This hydrogeological
      setting results in spring water discharges that closely follow meteoric water
      recharge patterns, leading to low-flow periods concentrated in the summer/early
      autumn. Therefore, the springs' outflow can be very sensitive to a shortage in
      water recharge, as it was the case in 2003 and 2017, when a prolonged period of
      drought caused severe water management issues. This work analyses how a group of
      such springs responds to climate change. In particular, we first validated a
      hydrological rainfall-runoff model on the basis of daily discharge data collected
      between 2013 and 2016. Then, outflows were simulated for baseline (1984-2013) and
      future periods (2021-2050) using weather data provided by five RCM-GCM
      combinations. Finally, we performed statistical analyses aiming to examine the
      intra-annual variability in discharge rates, low-flow indices, flow-duration
      curves and the length of low-flows. Results show no evidence of change in mean
      annual discharges, but future climate estimates suggest a slight change to
      seasonal discharges in the future, with a marked increase of discharge during
      winter and spring, and a decrease in summer and autumn. Q(95) and 7Q10 low-flow
      indices (i.e. the daily discharge exceeded 95% of the time and the minimum weekly
      discharge associated with a 10-year recurrence interval, respectively) are
      significantly affected by the climate change (-21.8% and -25.0%, respectively),
      while droughts are expected to be more frequent: the number of years with a
      consecutive low-flow between 51 and 100days to increase by a third, and between
      101 and 150 to duplicate.

PMID- 29220762
TI  - Foundations of the participatory approach in the Mekong River basin management.
AB  - Integrated Water Resource Management (IWRM) was acknowledged as a leading concept
      in the water management for the last two decades by academia, political decision
      makers and experts. It strongly promotes holistic management and participatory
      approaches. The flexibility and adaptability of IWRM concept are especially
      important for large, transboundary river basins - e.g. the Mekong river basin -
      where natural processes and hazards, as well as, human-made "disasters" are
      demanding for a comprehensive approach. In the Mekong river basin, the
      development and especially the enforcement of one common strategy has always been
      a struggle. The past holds some unsuccessful experiences. In 2016 Mekong River
      Commission published IWRM-based Basin Development Strategy 2016-2020 and The
      Mekong River Commission Strategic Plan 2016-2020. They should be the main guiding
      document for the Mekong river development in the near future. This study analyzes
      how the concept of public participation resembles the original IWRM participatory
      approach in these documents. Therefore, IWRM criteria for public participation in
      international literature and official documents from the Mekong river basin are
      compared. As there is often a difference between "de jure" and "de facto"
      implementation of public participation in management concepts, the perception of
      local stakeholders was assessed in addition. The results of social survey give an
      insight if local people are aware of Mekong river basin development and present
      their dominant attitudes about the issue. The findings enable recommendations how
      to mitigate obstacles in the implementation of common development strategy.

PMID- 29220763
TI  - Concentration and spectroscopic characteristics of DOM in surface runoff and
      fracture flow in a cropland plot of a loamy soil.
AB  - Being crucial for predicting the impact of source inputs on a watershed in
      rainfall events, an understanding of the dynamics and characteristics of
      dissolved organic matter (DOM) export from the soil under particular land use
      types, particularly those associated with underground flows is still largely
      lacking. A field study was carried out using a 1500m2 slope farmland plot in the
      hilly area of Sichuan Basin, Southwest China. The discharge of surface runoff and
      fracture flow was recorded and samples were collected in four representative
      rainfall events. For DOM characterization, concentration of dissolved organic
      carbon (DOC) and absorbance/excitation-emission matrix (EEM) fluorescence were
      analyzed. Soil water potential was also determined using tensiometers for
      understanding the runoff generation mechanisms. The DOC values for both surface
      and fracture flow showed significant responses to rainfall, with hydrological
      path being the primary factor in determining DOM dynamics. EEM-PARAFAC analyses
      indicated that the soil DOM mainly consisted of two terrestrial humic-like
      components with peaks located at Ex/Em 270(380)/480nm (C1) and 250(320)/410nm
      (C2), respectively. Concentrations of these components also responded strongly to
      rainfall, fluctuating in good agreement with the corresponding DOCs. Although
      there was no change in the presence of the components themselves, their relative
      distributions varied during precipitation, with the C1/C2 ratio increasing with
      the proportion of soil pre-event water. As the dynamic changes of soil DOM
      characteristics can be successfully captured using spectroscopic techniques, they
      may serve as a tracer for understanding hydrological paths based on their
      potential correlations with water source differences during rains.

PMID- 29220769
TI  - Influence of urban pattern on inundation flow in floodplains of lowland rivers.
AB  - The objective of this paper is to investigate the respective influence of various
      urban pattern characteristics on inundation flow. A set of 2000 synthetic urban
      patterns were generated using an urban procedural model providing locations and
      shapes of streets and buildings over a square domain of 1*1km2. Steady two
      dimensional hydraulic computations were performed over the 2000 urban patterns
      with identical hydraulic boundary conditions. To run such a large amount of
      simulations, the computational efficiency of the hydraulic model was improved by
      using an anisotropic porosity model. This model computes on relatively coarse
      computational cells, but preserves information from the detailed topographic data
      through porosity parameters. Relationships between urban characteristics and the
      computed inundation water depths have been based on multiple linear regressions.
      Finally, a simple mechanistic model based on two district-scale porosity
      parameters, combining several urban characteristics, is shown to capture
      satisfactorily the influence of urban characteristics on inundation water depths.
      The findings of this study give guidelines for more flood-resilient urban
      planning.

PMID- 29220771
TI  - Estimation of refueling emissions based on theoretical model and effects of E10
      fuel on refueling and evaporative emissions from gasoline cars.
AB  - The effects of Reid vapor pressure (RVP) on refueling emissions and the effects
      of ethanol 10% (E10) fuel on refueling and evaporative emissions were observed
      using six cars and seven fuels. The results indicated that refueling emissions
      can be reproduced by a simple theoretical model in which fuel vapor in the empty
      space in the tank is pushed out by the refueling process. In this model, the
      vapor pressures of fuels can be estimated by the Clausius-Clapeyron equation as a
      function of temperature. We also evaluated E10 fuel in terms of refueling and
      evaporative emissions, excluding the effect of contamination of ethanol in the
      canister. E10 fuel had no effect on the refueling emissions in cases without
      onboard refueling vapor recovery. E10 showed increased permeation emissions in
      evaporative emissions because of the high permeability of ethanol. And with E10
      fuel, breakthrough emissions appeared earlier but broke through slower than
      normal fuel. Finally, canisters could store more fuel vapor with E10 fuel.

PMID- 29220764
TI  - The changing pattern of urban flooding in Guangzhou, China.
AB  - Extensive research has focused on modelling and analysis of urban flooding in
      relatively small catchments. Findings in small areas tend to be site-specific,
      and may not be applicable to larger study areas. Larger scale studies can
      identify general patterns and influential factors; however, few studies have
      investigated urban flooding on a larger scale such as a metropolitan area. In
      this study, we explored the spatial-temporal patterns of urban flooding during
      the period of 2009-2015 in the central area of Guangzhou, China. Under the
      framework of Pressure (precipitation and impervious surface)-State (urban
      flooding)-Response (drainage improvement), we evaluated reasons for the State
      change and effectiveness of the Response. Overall the urban flooding state showed
      a fluctuating and improving trend. The fluctuation of the flooding state trend is
      due to precipitation variation, and the improving trend is attributed to drainage
      improvement. Furthermore, drainage improvement in the upstream area had led to
      new flooding in the downstream area. It is evident that the mitigation effect of
      urban flooding in Guangzhou varied significantly across the city. It is further
      suggested to regularly collect urban flooding records in cities with flood risk,
      so that more appropriate policies and measures about urban flooding mitigation
      can be developed.

PMID- 29220765
TI  - Transient disturbance of engineered ZnO nanoparticles enhances the resistance and
      resilience of anammox process in wastewater treatment.
AB  - The increasing use of engineered nanoparticles (NPs) in consumer and industrial
      products raises concerns about their environmental impacts, but their potential
      influence on anaerobic ammonium oxidation (anammox) process in wastewater
      treatment remains unknown. In this study, the response of granule-based anammox
      reactor to different loads of ZnONPs was investigated. The introduction of 1-5mgL
      1 ZnONPs did not affect reactor performance, but 90% of the nitrogen removal
      capacity was deprived by a shock of 10mgL-1 ZnONPs within 3days. Anammox activity
      was significantly inhibited, but no significant stimulation of intracellular
      reactive oxygen species (ROS) production or extracellular lactate dehydrogenase
      (LDH) activity was observed. The inhibition was thus mainly due to the
      accumulation of toxic Zn(II) ions in anammox biomass. However, the resistance and
      resilience of this anammox reactor to ZnONPs were enhanced by intermittent
      perturbations in the mode of "shock-recovery". The up-regulated abundance of
      Zn(II)-exporter ZntA might contribute to the enhanced resistance. In addition,
      these repeated transient disturbances improved the functional specificity of the
      anammox community despite the reduction of its diversity. Overall, these results
      may provide useful references for evaluating and controlling the risk of NPs to
      anammox process.

PMID- 29220770
TI  - Role of methanogenesis on the biotransformation of organic micropollutants during
      anaerobic digestion.
AB  - Several studies showed that some organic micropollutants (OMPs) are
      biotransformed during anaerobic digestion (AD). Yet, most of them aim at
      reporting removal efficiencies instead of understanding the biotransformation
      process. Indeed, how each of the main AD stages (i.e., hydrolysis, acidogenesis,
      and methanogenesis) contribute to OMP biotransformation remains unknown. This
      study focuses on investigating the role of methanogenesis, the most
      characteristic step of AD, to OMP removal. More specifically, the sorption and
      the biotransformation of 20 OMPs by methanogenic biomass were analyzed
      determining their concentrations in both liquid and solid phases. Sorption onto
      methanogenic biomass displayed a similar behavior as reported for digested
      sludge. Most of the OMPs were biotransformed to a medium extent (35-70%) and only
      sulfamethoxazole was completely removed. Comparing these results with those
      reported for the complete AD process, methanogenesis was proven to play a key
      role, accounting for more than 50% of the OMP biotransformation (except for
      roxithromycin) during AD. An increase in the organic loading rate from 1 to
      2gCOD/Ld, typical loads employed in sewage sludge anaerobic digesters, did not
      exert a clear cometabolic effect on the OMPs biotransformation. It is
      hypothesized that biotransformation occurs in both liquid and solid phases
      because no link between the partition coefficient (Kd) and the overall
      biotransformation efficiency was found. These findings allow a better
      understanding of the OMPs fate under anaerobic conditions, which is necessary to
      design efficient biological mitigation strategies.

PMID- 29220772
TI  - Column-integrated aerosol optical properties of coarse- and fine-mode particles
      over the Pearl River Delta region in China.
AB  - The sun-photometer data from 2011 to 2013 at Panyu site (Panyu) and from 2007 to
      2013 at Dongguan site (Dg) in the Pearl River Delta region, were used for the
      retrieving of the aerosol optical depth (AOD), single scattering albedo (SSA),
      Angstrom exponent (AE) and volume size distribution of coarse- and fine-mode
      particles. The coarse-mode particles presented low AOD (ranging from 0.05+/-0.03
      to 0.08+/-0.05) but a strong absorption property (SSA ranged from 0.70+/-0.03 to
      0.90+/-0.02) for the wavelengths between 440 and 1020nm. However, these coarse
      particles accounted for <10% of the total particles. The AOD of fine particles
      (AODf) was over 3 times as large as that of coarse particles (AODc). The fine
      particles SSA (SSAf) generally decreased as a function of wavelength, and the
      relatively lower SSAf value in summer was likely to be due to the stronger solar
      radiation and higher temperature. More than 70% of the aerosols at Panyu site
      were dominated by fine-mode absorbing particles, whereas about 70% of the
      particles at Dg site were attributed to fine-mode scattering particles. The
      differences of the aerosol optical properties between the two sites are likely
      associated with local emissions of the light-absorbing carbonaceous aerosols and
      the scattering aerosols (e.g., sulfate and nitrate particles) caused by the gas
      phase oxidation of gaseous precursors (e.g., SO2 and NO2). The size distribution
      exhibited bimodal structures in which the accumulation mode was predominant. The
      fine-mode volume showed positive dependence on AOD (500nm), and the growth of
      peak value of the fine-mode volume was higher than that of the coarse volume.
      Both the AOD and SSA increased with increasing relative humidity (RH), while the
      AE decreased with increasing RH. These correlations imply that the aerosol
      properties are greatly modified by condensation growth.

PMID- 29220767
TI  - Morphological and biomechanical response to eutrophication and hydrodynamic
      stresses.
AB  - Eutrophication and hydrodynamics determine the final distribution patterns of
      aquatic macrophytes; however, there is limited available knowledge regarding
      their interactive effects. Morphological and biomechanical responses to
      eutrophication and hydrodynamic stresses were assessed by sampling five abundant
      and dominant species, Potamogeton maackianus, P. pectinatus, P. lucens,
      Ceratophyllum demersum and Myriophyllum spicatum, in three macrophyte beds in
      Lake Erhai, Yunnan Province, China: one exposed to eutrophication and moderate
      southeast (SE) wind; one with mesotrophication, but sheltered by the lakeshore,
      with weak wind disturbance; and one with meso-eutrophication and strong SE wind.
      The results showed significant interactive effects of eutrophication and
      hydrodynamics on most biomechanical traits and some morphological traits,
      suggesting that aquatic macrophytes preferentially undergo biomechanical
      adjustments to resist the coexisting eutrophication and hydrodynamic stresses. In
      particular, hydrodynamics increased both the tensile force and tensile strain of
      P. maackianus under meso-eutrophication and dramatically decreased them in
      eutrophic areas, suggesting that eutrophication triggers mechanical failure in
      this species. Additionally, P. pectinatus, C. demersum and M. spicatum showed the
      lowest and highest values for the biomechanical variables (greater values for M.
      spicatum) in the most eutrophic and hydrodynamic areas, respectively, implying
      that increases in hydrodynamics primarily induce mechanical damage in eutrophic
      species. The plants generally exhibited greater tensile strain in both shallow
      and deep waters and the greatest tensile force at moderate depths. The stem cross
      sectional area, plant height, stem length, internode length, and branch traits
      were all responsible for determining the biomechanical variables. This study
      reveals that hydrodynamic changes primarily induce mechanical damage in eutrophic
      species, whereas eutrophication triggers mechanical damage in sensitive species.

PMID- 29220766
TI  - A global framework to model spatial ecosystems exposure to home and personal care
      chemicals in Asia.
AB  - This paper analyzes spatially ecosystem exposure to home and personal care (HPC)
      chemicals, accounting for market data and environmental processes in hydrological
      water networks, including multi-media fate and transport. We present a global
      modeling framework built on ScenAT (spatial scenarios of emission), SimpleTreat
      (sludge treatment plants), and Pangea (spatial multi-scale multimedia fate and
      transport of chemicals), that we apply across Asia to four chemicals selected to
      cover a variety of applications, volumes of production and emission, and physico
      chemical and environmental fate properties: the anionic surfactant linear
      alkylbenzene sulphonate (LAS), the antimicrobial triclosan (TCS), the personal
      care preservative methyl paraben (MeP), and the emollient
      decamethylcyclopentasiloxane (D5). We present maps of predicted environmental
      concentrations (PECs) and compare them with monitored values. LAS emission levels
      and PECs are two to three orders of magnitude greater than for other substances,
      yet the literature about monitored levels of LAS in Asia is very limited. We
      observe a good agreement for TCS in freshwater (Pearson r=0.82, for 253 monitored
      values covering 12 streams), a moderate agreement in general, and a significant
      model underestimation for MeP in sediments. While most differences could be
      explained by uncertainty in both chemical/hydrological parameters (DT50water,
      DT50sediments, Koc, foc, TSS) and monitoring sites (e.g. spatial/temporal
      design), the underestimation of MeP concentrations in sediments may involve
      potential natural sources. We illustrate the relevance of local evaluations for
      short-lived substances in fresh water (LAS, MeP), and their inadequacy for
      substances with longer half-lives (TCS, D5). This framework constitutes a
      milestone towards higher tier exposure modeling approaches for identifying areas
      of higher chemical concentration, and linking large-scale fate modeling with
      (sub) catchment-scale ecological scenarios; a major limitation in model accuracy
      comes from the discrepancy between streams routed on a gridded, 0.5 degrees *0.5
      degrees  global hydrological network and actual locations of streams and
      monitoring sites.

PMID- 29220768
TI  - Analysis of airborne Olea pollen in Cartagena (Spain).
AB  - Olive cultivation is of great importance in Southern Europe but olive pollen is
      the leading cause of allergy in many regions where it is grown. The best
      preventive measure for allergic patients is to avoid exposure. Thus,
      aerobiological monitoring networks must supply realistic pollen classes for the
      different types of allergic pollen. Even though those pollen classes are defined,
      they do not necessarily fit local data. Altogether, they should use predictive
      models to assess flowering intensity in advance. In this study, the Olea pollen
      degree of exposure classes (OPDEC) are defined based on percentiles and a
      predictive model is suggested for Cartagena, Spain. 24year (1993-2016) Olea
      pollen counts series was used to characterize the Main Pollen Season (MPS). The
      aerobiological samples were processed following the methodology proposed by Hirst
      and developed by the Spanish Aerobiology Network. The aerobiological database was
      completed with the meteorological data supplied by AEMET (Spanish State
      Meteorological Agency). MPS evolution over time, and its relation with
      temperature and rainfall, has been analysed. The study showed an increase in MPS
      duration and the amount of Olea pollen grains collected both in MPS and the peak
      day. The OPDEC should fit local data to improve preventive measures. Based on the
      24year series, the proposed OPDEC for Cartagena are: Low (<=10grains/m3), Medium
      (between 10 and 50grains/m3), High (between 51 and 100grains/m3) and Very High
      (>=100grains/m3). Olea pollen estimations in the MPS and in the peak day were
      obtained by means of three Regression Methods and climatic factors. The analysis
      reveals that the Bagging for Regression Trees (BRT) method is a good predictive
      alternative and stablishes the importance for each meteorological variable.

PMID- 29220774
TI  - Mitigating land pollution through pesticide packages - The case of a collection
      scheme in Rural China.
AB  - Pesticide packages that are discarded on agricultural land can contaminate water
      bodies and pose a threat to the environment and human health. Little is known
      about how developing countries deal with this kind of land pollution. While in
      developed countries, packages are collected by professional organizations, the
      smallholder context in developing countries makes the collection of this waste
      much more difficult. This paper introduces and analyses a successful Pesticide
      Package Collection Scheme in one of the poorest regions in China, i.e. Guangxi
      Province. The purpose of the paper is to analyze and discuss how such a scheme
      can be established by multiple actors. The paper finds that the underlying
      success factors for establishing such a scheme are 1.) that a scheme piggy-bags
      on existing economic structures that reach out to farmers (e.g. associations);
      2.) that the scheme itself facilitates actors' exchange of resources to establish
      a temporary resource equilibrium; 3.) that all stakeholders obtain returns on
      their investment, even if the quality and time scale of these returns may differ.
      The initiation of the scheme by a pesticide company however increased both its
      political and market influence. Caution hence has to be paid to whether the short
      term improvement in land pollution happens at the expense of a dependency on and
      increased use of certain kinds of pesticides.

PMID- 29220773
TI  - Climate change and dengue fever transmission in China: Evidences and challenges.
AB  - Dengue Fever (DF) has become one of the most serious infectious diseases in
      China. Dengue virus and its vector (Aedes mosquito) are known to be sensitive to
      climate condition. Climate impacts DF through affecting three essential
      bioecological aspects: DF virus, vector (mosquito) and DF transmission
      environment. Weather-based DF model, mosquito model and climate model are the
      three pillars to help the prediction of DF distribution. Through a systematic
      review of literature between 1980 and 2017, this paper summarizes empirical
      evidences in China on the impact of climate change on DF; it further reviews the
      related DF incidence models and their findings on how changes in weather factors
      may impact DF occurrences in China. Compared with some well-known research
      projects in the western countries, there is a lack of knowledge in China
      regarding how the spatiotemporal distribution of DF will respond to climate
      change. However, being able to predict DF distribution is key to China's efforts
      to prevent and control DF transmission. We conclude this paper by recommending
      four focused areas for China: promoting more advanced research on the
      relationship between extreme weather events and DF, developing regional-specific
      models for the high risk regions of DF in south China, encouraging
      interdisciplinary collaboration between climate studies and health services, and
      enhancing public health education and management at national, regional and local
      levels.

PMID- 29220779
TI  - Lower levels of serum copper in patients with Alzheimer's dementia: A controlled
      study from India.

PMID- 29220776
TI  - Analysis of metabolites of organophosphate and pyrethroid pesticides in human
      urine from urban and agricultural populations (Catalonia and Galicia).
AB  - Isotope dilution solid phase extraction UPLC-MS/MS has been used to develop a
      robust and rapid methodology for the determination of eight specific metabolites
      of organophosphate and pyrethroid pesticides in human urine. The use of
      methanol:acetone (25:75v/v) affords an improvement in extraction efficiency in
      comparison to these individual solvents. The use of synthetic urine improves
      selectivity and limits of detection for the calibration straight lines. The
      method provides detection limits of 14-69pg/ml and 18-19pg/ml for the
      organophosphate and pyrethroid metabolites, respectively. Urine analyses of these
      metabolites in urban non-occupationally exposed individuals and farm workers
      shows that ingestion of these pesticides occurred in both populations. The
      concentrations of organophosphate pesticide metabolites in the latter were
      twofold than those from non-exposed populations.

PMID- 29220778
TI  - Quantitative assessment of Naegleria fowleri and fecal indicator bacteria in
      brackish water of Lake Pontchartrain, Louisiana.
AB  - Brackish water samples from Lake Pontchartrain in Louisiana were assessed for the
      presence of pathogenic amoeba Naegleria fowleri, which causes primary amoebic
      meningoencephalitis (PAM). In our study, quantitative polymerase chain reaction
      (qPCR) methods were used to determine N. fowleri, E. coli, and enterococci in
      water collected from Lake Pontchartrain. N. fowleri target sequence was detected
      in 35.4% (56/158) of the water samples from ten sites around the lake.
      Statistically significant positive correlations between N. fowleri concentration
      and water temperature as well as E. coli (qPCR) were observed. Multiple linear
      regression (MLR) model shows seasonal factor (summer or winter) has significant
      effect on the concentration of N. fowleri, E. coli and enterococci (qPCR)
      concentration. Significant positive relationships between E. coli and enterococci
      was observed from both qPCR (r=0.25) and culture based method (r=0.54).
      Meanwhile, significant positive correlation between qPCR and culture based
      methods for enterococci concentration was observed (r=0.33). In our study, water
      temperature and E. coli concentration were indicative of N. fowleri
      concentrations in brackish water environment. Future research is needed to
      determine whether sediment is a source of N. fowleri found in the water column.

PMID- 29220780
TI  - The catatonic pupil: An unprivileged entity.

PMID- 29220777
TI  - Scenario modelling of land use/land cover changes in Munessa-Shashemene landscape
      of the Ethiopian highlands.
AB  - Models under a set of scenarios are used to simulate and improve our
      understanding of land use/land cover (LULC) changes, which is central for
      sustainable management of a given natural resource. In this study, we simulated
      and examined the possible future LULC patterns and changes in Munessa-Shashemene
      landscape of the Ethiopian highlands covering four decades (2012-2050) using a
      spatially explicit GIS-based model. Both primary and secondary sources were
      utilized to identify relevant explanatory variables (drivers) and LULC datasets
      for the model. Three alternative scenarios, namely Business As Usual (BAU),
      Forest Conservation and Water Protection (FCWP) and Sustainable Intensification
      (SI) were used. The simulated LULC map of 2012 was compared with the actual for
      model validation and showed a good consistency. The results revealed that areas
      of croplands will increase widely under the BAU scenario and would expand to the
      remaining woodlands, natural forests and grasslands, reflecting vulnerability of
      these LULC types and potential loss of associated ecosystem service values
      (ESVs). FCWP scenario would bring competition among other LULC types,
      particularly more pressure to the grassland ecosystem. Hence, the two scenarios
      will result in severe LULC dynamics that lead to serious environmental crisis.
      The SI scenario, with holistic approach, demonstrated that expansion of croplands
      could vigorously be reduced, remaining forests better conserved and degraded land
      recovered, resulting in gains of the associated total ESVs. We conclude that a
      holistic landscape management, i.e. SI, is the best approach to ensure expected
      production while safeguarding the environment of the studied landscape and
      elsewhere with similar geographic settings. Further study is suggested to
      practically test our framework through a research for development approach in a
      test site so that it can be used as a model area for effective use and
      conservation of our natural resources.

PMID- 29220783
TI  - A study to compare the differences between genders in psychiatric comorbidities
      in individuals with psychoses.
AB  - BACKGROUND: Psychiatric comorbidities worsen the outcome and increase severity of
      suffering in psychotic disorders. Gender differences have also been found to
      impact the severity and outcome in psychoses. In this background, this study
      attempted to compare psychiatric comorbidity between genders. AIMS AND
      OBJECTIVES: The aim was to compare psychiatric co-morbidity between men and women
      with psychotic disorders. METHODOLOGY: A descriptive cross sectional study design
      was used. Data was collected through clinical interviews using standardized tools
      as well as the current case records. We used the MINI neuropsychiatric interview
      5.0 to generate an ICD 10 diagnosis for primary psychotic illness and psychiatric
      comorbidity. PANSS was used to assess severity. Calgary Depression Scale for
      Schizophrenia, Hamilton Anxiety rating scale, Yale Brown Obsessive Compulsive
      Scale, Alcohol Use Disorders Identification Test and Fagerstrom Nicotine
      Tolerance Questionnaire were used to study comorbidity. RESULTS: 100 patients
      were included in the study. 61% of the population had a psychiatric comorbidity.
      42% of the men had significantly more multiple psychiatric comorbidities as
      compared to 7% among women. Men had significantly more substance use than women.
      Age of onset of psychosis was not found to be different between men and women.
      CONCLUSION: In this study men had more psychiatric comorbidity than women, owing
      to greater levels of substance use disorders and anxiety disorders. This could be
      one of the possible reasons for differing outcomes between men and women with
      psychotic disorders thus indicating need for systematic future researching in
      psychiatric comorbidities in psychoses.

PMID- 29220781
TI  - Activities of daily living in hospitalized patients with mental disorders.

PMID- 29220785
TI  - Metagenomic exploration reveals a marked change in the river resistome and
      mobilome after treated wastewater discharges.
AB  - Mobile genetic elements (MGEs) are key agents in the spread of antibiotic
      resistance genes (ARGs) across environments. Here we used metagenomics to compare
      the river resistome (collection of all ARGs) and mobilome (e.g., integrases,
      transposases, integron integrases and insertion sequence common region "ISCR"
      elements) between samples collected upstream (n = 6) and downstream (n = 6) of an
      urban wastewater treatment plant (UWWTP). In comparison to upstream metagenomes,
      downstream metagenomes showed a drastic increase in the abundance of ARGs, as
      well as markers of MGEs, particularly integron integrases and ISCR elements.
      These changes were accompanied by a concomitant prevalence of 16S rRNA gene
      signatures of bacteria affiliated to families encompassing well-known human and
      animal pathogens. Our results confirm that chronic discharges of treated
      wastewater severely impact the river resistome affecting not only the abundance
      and diversity of ARGs but also their potential spread by enriching the river
      mobilome in a wide variety of MGEs.

PMID- 29220782
TI  - Mindfulness-based interventions for chronic pain: Evidence and applications.
AB  - Chronic pain is estimated to occur in from 5.5% to 33% of the world's adult
      population (Gureje et al., 1998). Chronic pain is frequently treated with
      opiates, which has produced an opiate addiction crisis (Dowell et al., 2016).
      Several non-pharmacological treatment alternatives can help manage chronic pain.
      There is moderate evidence that mindfulness-based interventions (MBIs) such as
      meditation, yoga, and stress reduction lower the perception of pain, increase
      mobility, improve functioning and well-being. By integrating MBIs and other
      therapeutic interventions in a multi-disciplinary pain management plan,
      clinicians can improve treatment outcomes and potentially decrease pain-related
      medication utilization.

PMID- 29220775
TI  - SiO2 nanomaterial as a tool to improve Hordeum vulgare L. tolerance to nano-NiO
      stress.
AB  - This work was designed to assess the potential role of silicon dioxide
      nanomaterial (nano-SiO2) in enhancing barley's tolerance to nickel oxide
      nanomaterial (nano-NiO). For this purpose, plants were grown for 14days under
      nano-NiO (120mgkg-1) single and co-exposure with nano-SiO2 (3mgkg-1). The
      exposure of barley to nano-NiO caused a significant decrease in growth-related
      parameters and induced a negative response on the photosynthetic apparatus.
      However, upon nano-SiO2 co-exposure, the inhibitory effects of nano-NiO were
      partially reduced, with lower reductions in fresh and dry biomass, and with the
      recovery of the photosynthesis-related parameters. Plants growing under nano-NiO
      stress showed an overproduction of superoxide anion (O2.-), which favored the
      occurrence of oxidative stress and the enhancement of lipid peroxidation (LP),
      but the co-treatment with nano-SiO2 reverted this tendency, generally lowering or
      maintaining the levels of LP and stimulating the redox pathway of thiols. The
      evaluation of the antioxidant (AOX) system revealed that nano-NiO induced the
      accumulation of proline, along with a decrease in ascorbate in leaves.
      Furthermore, superoxide dismutase (SOD) activity was significantly enhanced and
      catalase (CAT) and ascorbate peroxidase (APX) seemed to have a pivotal role in
      H2O2 detoxification in leaves and roots, respectively. The response of the AOX
      system was even more prominent upon nano-SiO2 co-exposure, reinforcing the
      ameliorating functions of this nanomaterial. Overall, the present study
      highlighted the protective role of nano-SiO2 in barley plants under nano-NiO
      stress, possibly due to the Si-mediated protection against oxidative stress, by a
      more proactive performance of the plant AOX system.

PMID- 29220786
TI  - Magnetic susceptibility of spider webs as a proxy of airborne metal pollution.
AB  - The purpose of this pilot study was to test spider webs as a fast tool for
      magnetic biomonitoring of air pollution. The study involved the investigation of
      webs made by four types of spiders: Pholcus phalangioides (Pholcidae), Eratigena
      atrica and Agelena labirynthica (Agelenidae) and Linyphia triangularis
      (Linyphiidae). These webs were obtained from outdoor and indoor study sites.
      Compared to the clean reference webs, an increase was observed in the values of
      magnetic susceptibility in the webs sampled from both indoor and outdoor sites,
      which indicates contamination by anthropogenically produced pollution particles
      that contain ferrimagnetic iron minerals. This pilot study has demonstrated that
      spider webs are able to capture particulate matter in a manner that is equivalent
      to flora-based bioindicators applied to date (such as mosses, lichens, leaves).
      They also have additional advantages; for example, they can be generated in
      isolated clean habitats, and exposure can be monitored in indoor and outdoor
      locations, at any height and for any period of time. Moreover, webs are
      ubiquitous in an anthropogenic, heavily polluted environment, and they can be
      exposed throughout the year. As spider webs accumulate pollutants to which humans
      are exposed, they become a reliable source of information about the quality of
      the environment. Therefore, spider webs are recommended for magnetic
      biomonitoring of airborne pollution and for the assessment of the environment
      because they are non-destructive, low-cost, sensitive and efficient.

PMID- 29220791
TI  - Design, synthesis and biological activity evaluation of novel 4-subtituted 2
      naphthamide derivatives as AcrB inhibitors.
AB  - A novel series of 4-substituted 2-naphthamide derivatives were designed,
      synthesized and evaluated for their biological activity. In particular, the
      ability of the compounds to potentiate the action of antibiotics, to inhibit Nile
      Red efflux and to target AcrB specifically was investigated. The results
      indicated that most of the 4-substituted 2-naphthamide derivatives were able to
      synergize with the antibiotics tested, and inhibit Nile Red efflux by AcrB in the
      resistant phenotype. Subsequent exclusion of compounds with off target effects
      such as outer- or inner membrane permeabilization identified compounds 7c, 7g,
      12c, 12i and 13g as efflux pump inhibitors (EPIs). Particularly, compounds 7c, 7g
      and 12i were found to be the most potent EPIs, which synergized with the two
      substrates tested at lower concentrations than that of parent A3, demonstrating
      an improvement in potency as compared to A3. Additionally, when the outer
      membrane of E. coli was permeabilized, compound 12c displayed a huge increase in
      efficacy and was able to synergize with erythromycin at a concentration that was
      16 times lower than that of the parent A3. Hence we were able to design and
      synthesize compounds that displayed significant increase in efficacy as EPIs
      against AcrB.

PMID- 29220788
TI  - Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer
      immunotherapy.
AB  - There has been great attention on indoleamine-2,3-dioxygenase 1 (IDO1) around
      cancer immunotherapy because of its role in enabling cancers to evade the immune
      system. The most recent spurt of high potent IDO1 inhibitors has been driven by
      the solution of the increased crystal structures of inhibitors with IDO1. Though
      the structural information of the active site of IDO1 obtained from the crystals
      are quite similar, the structures of reported potent inhibitors are quite
      different. Besides, while thousands of bioactive small molecule inhibitors of
      IDO1 exist, to date, only five compounds have entered clinical trials. In an
      effort to obtain more clinical drugs targeting IDO1, more comprehensive
      understanding of the active site of IDO1 and the structures of existing potent
      IDO1 inhibitors are necessary. Thus, this review mainly focus on the key features
      reported from specific crystal structures of IDO1 and an overview of the most
      recently developed IDO1 inhibitors under investigation and their other derived
      applications which may contribute to a better usage in cancer immunotherapy.

PMID- 29220793
TI  - Design, synthesis, and biological evaluation of novel highly selective polo-like
      kinase 2 inhibitors based on the tetrahydropteridin chemical scaffold.
AB  - Polo-like kinase 2 (Plk2) is a potential target for the treatment of cancer,
      which displays an important role in tumor cell proliferation and survival. In
      this report, according to the analysis of critical amino acid residue differences
      among Plk1, Plk2 and Plk3, and structure-based drug design strategies, two novel
      series of selective Plk2 inhibitors based on tetrahydropteridin chemical scaffold
      were designed and synthesized to target two specific residues, Lys86 and Tyr161
      of Plk2. All compounds were evaluated for their inhibitory activity against Plk1
      Plk3 and the cellular inhibition activity on six different human cancer cell
      lines. All efforts led to the identification of the most potent compounds C2
      (3.40 nM against Plk2) and C21 (4.88 nM against Plk2) from the first and second
      series of selective Plk2 inhibitors respectively. Additionally, the selectivity
      of C21 over Plk1/3 was significantly increased with the selectivity indexes of
      12.57 and 910.06. Moreover, most of our compounds exhibited antitumor activity in
      the nanomolar range in the MTT assay, indicating that our compounds, especially
      C2 and C21 could be promising Plk2 inhibitors for further anticancer research.

PMID- 29220795
TI  - Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection
      properties.
AB  - Antioxidants have been the subject of intense research interest mainly due to
      their beneficial properties associated with human health and wellbeing. Phenolic
      molecules, such as naturally occurring Resveratrol and Vanillin, are well known
      for their anti-oxidant properties, providing a starting point for the development
      of new antioxidants. Here we report, for the first time, the synthesis of a
      number of new vanillin through the reductive amination reaction between vanillin
      and a selection of amines. All the compounds synthesised, exhibited strong
      antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c
      being the most active. The latter also demonstrated the ability to protect
      plasmid DNA from oxidative damage in the presence of the radical initiator AAPH.
      At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative
      damage (H2O2, 400 MUM) with both 1b and 2c. The presence of a tertiary amino
      group, along with the number of vanillin moieties in the molecule contribute for
      the antioxidant activity. Furthermore, the delocalization of the electron pair of
      the nitrogen and the presence of an electron donating substituent to enhance the
      antioxidant properties of this new class of compounds. In our opinion, vanillin
      derivatives 1b and 2c described in this work can provide a viable platform for
      the development of antioxidant based therapeutics.

PMID- 29220787
TI  - Assessment tools for microplastics and natural fibres ingested by fish in an
      urbanised estuary.
AB  - Microplastics and fibres occur in high concentrations along urban coastlines, but
      the occurrence of microplastic ingestion by fishes in these areas requires
      further investigation. Herein, the ingestion of debris (i.e., synthetic and
      natural fibres and synthetic fragments of various polymer types) by three benthic
      foraging fish species Acanthopagrus australis (yellowfin bream), Mugil cephalus
      (sea mullet) and Gerres subfasciatus (silverbiddy) in Sydney Harbour, Australia
      has been quantified and chemically speciated by vibrational spectroscopy to
      identify the polymer type. Ingested debris were quantified using gut content
      analysis, and identified using attenuated total reflectance Fourier transform
      infrared (ATR-FTIR) and Raman microspectroscopies in combination with principal
      component analysis (PCA). The occurrence of debris ingestion at the time of
      sampling ranged from 21 to 64% for the three species, and the debris number
      ranged from 0.2 to 4.6 items per fish for the different species, with ~53% of
      debris being microplastic. There was a significant difference in the amount of
      debris ingested among species; however, there was no difference among species
      when debris counts were standardised to fish weight or gut content weight,
      indicating that these species ingest a similar concentration of debris relative
      to their ingestion rate of other material. ATR-FTIR microspectroscopy
      successfully identified 72% of debris. Raman spectroscopy contributed an
      additional 1% of successful identification. In addition, PCA was used to non
      subjectively classify the ATR-FTIR spectra resulting in the identification of an
      additional 9% of the debris. The most common microplastics found were polyester
      (PET), acrylic-polyester blend, and rayon (semi-synthetic) fibres. The potential
      of using Raman microspectroscopy for debris identification was investigated and
      provided additional information about the nature of the debris as well as the
      presence of specific dyes (and hence potential toxicity).

PMID- 29220789
TI  - New estrogen receptor antagonists. 3,20-Dihydroxy-19-norpregna-1,3,5(10)-trienes:
      Synthesis, molecular modeling, and biological evaluation.
AB  - New estrogen receptor alpha (ERalpha) antagonists - 3,20-dihydroxy-19-norpregna
      1,3,5(10)-trienes containing an additional carbocyclic ring D' at the
      16alpha,17alpha positions - were synthesized. The effects of the new compounds on
      the MCF-7 breast cancer cells and ERalpha activation were investigated. All the
      steroids studied were synthesized starting from estrone methyl ether. The
      scaffold of compounds containing the six-membered ring D' was constructed via the
      Diels-Alder reaction of butadiene with 3-methoxy-19-norpregna-1,3,5(10),16
      tetraen-20-one 5. The hydrogenation of primary 16alpha,17alpha-cyclohexeno-adduct
      7 followed by 3-demethylation (by HBr-AcOH) and reduction of 20-oxo group (by
      LiAlH4) or in one step by DIBAH gave target mono- and dihydroxy steroids 9-11.
      The Corey-Chaykovsky reaction of the same 3-methoxy-19-norpregna-1,3,5(10),16
      tetraen-20-one 5 gave 16alpha,17alpha-methylene-substituted compound. The
      reaction of the latter with DIBAH immediately yielded 3,20-dihydroxy
      16alpha,17alpha-methyleno-19-norpregna-1,3,5(10)-triene 13. The same procedures
      using 3-methoxy-19-norpregna-1,3,5(10),16-tetraen-20-one 5 produced corresponding
      3,20-dihydroxy-16,17-19-norpregna-1,3,5(10)-triene 16 and 3,20-dihydroxy-19
      norpregna-1,3,5(10),16-tetraene 17. All compounds were fully characterized by 1D
      and 2D NMR, HRMS, and X-ray diffraction. The molecular docking showed that the
      target compounds can bind to ER, their binding mode being similar to that of
      natural estradiol. 16alpha,17alpha-Methylene- or unsubstituted compounds exhibit
      the highest cytotoxicity against MCF-7 cells, being simultaneously relatively
      weak ERalpha inhibitors. 3,20-Dihydroxy steroids containing the six-membered ring
      D' proved to be the most effective ERalpha inhibitors. These compounds displayed
      moderate cytotoxicity comparable of that of tamoxifen and showed no toxic effect
      on MCF-10A normal, nontumorigenic epithelial cells. The new ER antagonists were
      found to be good candidates for further testing as agents for the treatment and
      prevention of ERalpha-positive breast cancers.

PMID- 29220794
TI  - O2-(2,4-dinitrophenyl)diazeniumdiolates derivatives: Design, synthesis, cytotoxic
      evaluation and reversing MDR in MCF-7/ADR cells.
AB  - A series of O2-(2,4-dinitrophenyl)diazeniumdiolates derivatives were designed,
      synthesized and antiproliferative activities evaluated as novel nitric oxide (NO)
      releasing prodrugs that could be activated by glutathione S-transferases pi
      (GSTpi). Most of these derivatives exhibited significant antiproliferative
      activities compared to the reported NO-donor prodrug JS-K, among which compounds
      27 and 36 had superior potency with IC50 below 1 MUM. NO released amounts
      detection of all derivatives indicated that the antiproliferative activities were
      positively correlated with the levels of intracellular NO release in HCT116
      cells. The most potent compound 36 exhibited improved uncatalyzed stability of
      GSTpi. Additionally, 36 showed remarkably multidrug resistance reversal activity
      which reversed multidrug resistance of adriamycin (ADR) in MCF-7/ADR cells with
      IC50 from 84.94 MUM to 1.13 MUM.

PMID- 29220792
TI  - 4-Quinolone derivatives and their activities against Gram positive pathogens.
AB  - Gram-positive bacteria are responsible for a broad range of infectious diseases,
      and the emergency and wide spread of drug-resistant Gram-positive pathogens
      including MRSA and MRSE has caused great concern throughout the world. 4
      Quinolones which are exemplified by fluoroquinolones are mainstays of
      chemotherapy against various bacterial infections including Gram-positive
      pathogen infections, and their value and role in the treatment of bacterial
      infections continues to expand. However, the resistance of Gram-positive
      organisms to 4-quinolones develops rapidly and spreads widely, making them more
      and more ineffective. To overcome the resistance and reduce the toxicity,
      numerous of 4-quinolone derivatives were synthesized and screened for their in
      vitro and in vivo activities against Gram-positive pathogens, and some of them
      exhibited excellent potency. This review aims to outlines the recent advances
      made towards the discovery of 4-quinolone-based derivatives as anti-Gram-positive
      pathogens agents and the critical aspects of design as well as the structure
      activity relationship of these derivatives. The enriched SAR paves the way to the
      further rational development of 4-quinolones with a unique mechanism of action
      different from that of the currently used drugs to overcome the resistance, well
      tolerated and low toxic profiles.

PMID- 29220784
TI  - Physiological effects caused by microcystin-producing and non-microcystin
      producing Microcystis aeruginosa on medaka fish: A proteomic and metabolomic
      study on liver.
AB  - Cyanobacterial blooms have become a common phenomenon in eutrophic freshwater
      ecosystems worldwide. Microcystis is an important bloom-forming and toxin
      producing genus in continental aquatic ecosystems, which poses a potential risk
      to Human populations as well as on aquatic organisms. Microcystis is known to
      produce along with various bioactive peptides, the microcystins (MCs) that have
      attracted more attention notably due to their high hepatotoxicity. To better
      understand the effects of cyanobacterial blooms on fish, medaka fish (Oryzias
      latipes) were sub-chronically exposed to either non-MC-producing or MC-producing
      living strains and, for this latter, to its subsequent MC-extract of Microcystis
      aeruginosa. Toxicological effects on liver have been evaluated through the
      combined approach of histopathology and 'omics' (i.e. proteomics and
      metabolomics). All treatments induce sex-dependent effects at both cellular and
      molecular levels. Moreover, the modalities of exposure appear to induce
      differential responses as the direct exposure to the cyanobacterial strains
      induce more acute effects than the MC-extract treatment. Our histopathological
      observations indicate that both non-MC-producing and MC-producing strains induce
      cellular impairments. Both proteomic and metabolomic analyses exhibit various
      biological disruptions in the liver of females and males exposed to strain and
      extract treatments. These results support the hypothesis that M. aeruginosa is
      able to produce bioactive peptides, other than MCs, which can induce
      toxicological effects in fish liver. Moreover, they highlight the importance of
      considering cyanobacterial cells as a whole to assess the realistic environmental
      risk of cyanobacteria on fish.

PMID- 29220796
TI  - Purine analogs targeting the guanine riboswitch as potential antibiotics against
      Clostridioides difficile.
AB  - Riboswitches recently emerged as possible targets for the development of
      alternative antimicrobial approaches. Guanine-sensing riboswitches in the
      bacterial pathogen Clostridioides difficile (formerly known as Clostridium
      difficile) constitute potential targets based on their involvement in the
      regulation of basal metabolic control of purine compounds. In this study, we
      deciphered the structure-activity relationship of several guanine derivatives on
      the guanine riboswitch and determined their antimicrobial activity. We describe
      the synthesis of purine analogs modified in ring B as well as positions 2 and 6.
      Their biological activity was determined by measuring their affinity for the C.
      difficile guanine riboswitch and their inhibitory effect on bacterial growth,
      including a counter-screen to discriminate against riboswitch-independent
      antibacterial effects. Altogether, our results suggest that improvements in
      riboswitch binding affinity in vitro do not necessarily translate into improved
      antibacterial activity in bacteria, despite the fact that some structure-activity
      relationship was observed at least with respect to binding affinity.

PMID- 29220799
TI  - Accounting for adaptation and intensity in projecting heat wave-related
      mortality.
AB  - BACKGROUND: How adaptation and intensity of heat waves affect heat wave-related
      mortality is unclear, making health projections difficult. METHODS: We estimated
      the effect of heat waves, the effect of the intensity of heat waves, and
      adaptation on mortality in 209 U.S. cities with 168 million people during 1962
      2006. We improved the standard time-series models by incorporating the intensity
      of heat waves using excess heat factor (EHF) and estimating adaptation
      empirically using interactions with yearly mean summer temperature (MST). We
      combined the epidemiological estimates for heat wave, intensity, and adaptation
      with the Coupled Model Intercomparison Project Phase 5 (CMIP5) multi-model
      dataset to project heat wave-related mortality by 2050. RESULTS: The effect of
      heat waves increased with its intensity. Adaptation to heat waves occurred, which
      was shown by the decreasing effect of heat waves with MST. However, adaptation
      was lessened as MST increased. Ignoring adaptation in projections would result in
      a substantial overestimate of the projected heat wave-related mortality (by 277
      747% in 2050). Incorporating the empirically estimated adaptation into
      projections would result in little change in the projected heat wave-related
      mortality between 2006 and 2050. This differs regionally, however, with
      increasing mortality over time for cities in the southern and western U.S. but
      decreasing mortality over time for the north. CONCLUSIONS: Accounting for
      adaptation is important to reduce bias in the projections of heat wave-related
      mortality. The finding that the southern and western U.S. are the areas that face
      increasing heat-related deaths is novel, and indicates that more regional
      adaptation strategies are needed.

PMID- 29220798
TI  - Aegeline inspired synthesis of novel amino alcohol and thiazolidinedione hybrids
      with antiadipogenic activity in 3T3-L1 cells.
AB  - Excess adiposity is a hallmark of obesity, which is caused due to an imbalance
      between energy intake and energy consumed. Obesity is often associated with
      several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2
      diabetes. Earlier, our group had reported natural product Aegeline (amino
      alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti
      dyslipidemic compound. With this background, we synthesized a series of novel
      amino alcohol and thiazolidinedione hybrid molecules and studied their
      antiadipogenic activity. As a result, we have identified a potent hybrid compound
      12c as an inhibitor of adipocyte differentiation. The compound 12c inhibits lipid
      accumulation and adipogenesis in 3T3-L1 preadipocyte cell line. Exposure of
      compound 12c blocks mitotic clonal expansion and arrests cells in S-phase of cell
      cycle. Detailed analysis showed that compound 12c decreases expression of two
      major transcription factors that are involved in adipocyte differentiation,
      PPARgamma, C/EBPalpha, and other adipogenesis associated genes like aP2 and FAS.
      Thus, we concluded that compound 12c shows potential ability to inhibit adipocyte
      differentiation which can be used therapeutically for the treatment of obesity
      and its associated metabolic disorders.

PMID- 29220797
TI  - Primaquine hybrids as promising antimycobacterial and antimalarial agents.
AB  - Four series of primaquine (PQ) derivatives were screened for antitubercular and
      antiplasmodial activity: amides 1a-k, ureas 2a-s, semicarbazides 3a-c and bis
      ureas 4a-u. Antimycobacterial activity of PQ derivatives against Mycobacterium
      tuberculosis (MTB), M. avium complex (MAC) and M. avium subsp. paratuberculosis
      (MAP) were evaluated in vitro and compared with PQ and the standard
      antitubercular drugs. In general, the PQ derivatives showed higher potency than
      the parent compound. Most of the compounds of series 1 and 2 showed high activity
      against MAP, comparable or even higher than the relevant drug ciprofloxacin, and
      weak or no activity against MTB and MAC. bis-Trifluoromethylated cinnamamide 1k
      showed low cytotoxicity and high activity against all three Mycobacterium species
      and their activities were comparable or slightly higher than those of the
      reference drugs. PQ urea derivatives with hydroxyl, halogen and trifluoromethyl
      substituents on benzene ring 2f-p exerted very strong antimycobacterial activity
      towards all tested mycobacteria, stronger than PQ and the relevant standard
      drug(s). Unfortunately, these compounds had relatively high cytotoxicity, except
      bromo 2l and trifluoromethyl 2m, 2n derivatives. In general, meta-substituted
      derivatives were more active than analogues para-derivatives. Phenyl ureas were
      also more active than cycloalkyl or hydroxyalkyl ureas. Semicarbazide 3a showed
      similar activity as PQ, while the other two semicarbazides were inactive. Bis
      urea derivatives 4 were generally less active than the urea derivatives sharing
      the same scaffold, differing only in the spacer type. Out of 21 evaluated bis
      urea derivatives, only p-Cl/m-CF3 phenyl derivative 4p, benzhydryl derivatives 4t
      and 4u and bis-PQ derivative 4s showed high activity, higher than all three
      reference drugs. After comparison of activity and cytotoxicity, urea 2m and bis
      urea 4u could be considered as the most promising agents. Antimalarial potential
      of PQ derivatives in vitro against the liver stage of P. berghei was evaluated as
      well. 3-(4-Chlorophenyl)-1-[({4-[(6-methoxyquinolin-8
      yl)amino]pentyl}carbamoyl)amino]urea (4l) was the most active compound (IC50 = 42
      nM; cytotoxicity/activity ratio >2000). Our results bring new insights into
      development of novel anti-TB and antimalarial compounds.

PMID- 29220790
TI  - 2-Alkoxycarbonyl-3-arylamino-5-substituted thiophenes as a novel class of
      antimicrotubule agents: Design, synthesis, cell growth and tubulin polymerization
      inhibition.
AB  - Microtubules are recognized as crucial components of the mitotic spindle during
      cell division, and, for this reason, the microtubule system is an attractive
      target for the development of anticancer agents. Continuing our search strategy
      for novel tubulin targeting-compounds, a new series of 2-alkoxycarbonyl-3
      (3',4',5'-trimethoxyanilino)-5-aryl/heteroarylthiophene derivatives was designed,
      synthesized and demonstrated to act as tubulin polymerization inhibitors at the
      colchicine site. A structure-activity relationship study on the phenyl at the 5
      position of the thiophene ring was performed by introducing a variety of
      substituents containing electron-releasing and electron-withdrawing groups, with
      the 2-alkoxycarbonyl-3-(3',4',5'-trimethoxyanilino)thiophene scaffold being the
      minimum structural requirement for activity. Of the tested compounds, derivatives
      4a, 4c, 4i and 4k possessed the highest overall potency and displayed high
      antiproliferative activities at submicromolar concentrations, with IC50 values
      ranging from 0.13 to 0.84 MUM against four different cancer cell lines. Three
      agents (4a, 4c and 4i) in the present series had similar effects, and these were
      comparable to those of the reference compound combretastatin A-4 (CA-4) as
      inhibitors of tubulin assembly. The antitubulin effects correlated with the
      cytostatic activities and indicate that these compounds inhibit cell growth
      through inhibition of tubulin polymerization by binding at the colchicine site.
      Compound 4c, containing the 2'-thienyl ring at the 5-position of the 2
      methoxycarbonyl-3-(3',4',5'-trimethoxyanilino)thiophene scaffold, exhibited
      substantial antiproliferative activity with a mean IC50 value of 140 nM,
      inhibited tubulin polymerization with an IC50 value of 1.2 MUM, similar to that
      of CA-4 (IC50: 1.1 MUM), and induced apoptosis in HeLa cells.

PMID- 29220801
TI  - Assessment of temperature and ultraviolet radiation effects on sunburn incidence
      at an inland U.S. Beach: A cohort study.
AB  - BACKGROUND: Increases in outdoor temperature may lead to increases in sunburn,
      outdoor exposure, and skin cancer in human populations. OBJECTIVE: This study
      aimed to quantify sunburn incidence and risk for Ohio beachgoers exposed to
      varying outdoor conditions. METHODS: Sunburn incidence data were obtained through
      a prospective cohort study at East Fork Lake (Cincinnati, Ohio, USA). Recruitment
      occurred over 26 weekend days. Beach interviews and follow-up telephone
      interviews obtained exposure and health information. New sunburns were self
      reported 8-9 days post-enrollment. Survey data were paired with ultraviolet
      radiation (UVR) index and temperature data for statistical analysis. RESULTS:
      Among 947 beachgoers, new sunburns were reported in 18% of swimmers. Sunburn
      incidence was associated with temperature (odds ratio = 1.2; 95% CI: 1.1 - 1.4)
      and UVR index (odds ratio = 1.6; 95% CI: 1.0 - 2.5) in models adjusted for water
      exposure, arrival time, and beach visit frequency. Some evidence of a
      temperature+UVR interaction was observed. LIMITATIONS: Exposure and sunburn data
      were self-reported without clinical diagnosis and date of onset. The follow-up
      period enabled sunburns to be reported from a variety of days rather than only
      the beach visit day thereby limiting interpretation. Sun protection behaviors
      were not evaluated. CONCLUSIONS: Temperature and UVR influence sunburn frequency.
      Temperature, however was more strongly associated with sunburn in beachgoers than
      the nearest measured UVR index, suggesting future investigations are needed to
      better understand how temperature effects sunburn development. Interventions for
      decreasing sunburn are needed.

PMID- 29220800
TI  - Exposure to traffic-related air pollution and the composition of the gut
      microbiota in overweight and obese adolescents.
AB  - BACKGROUND: Traffic-related air pollution (TRAP) exposure has been linked to type
      2 diabetes and metabolic dysfunction in humans. Animal studies suggest that air
      pollutants may alter the composition of the gut microbiota, which may negatively
      impact metabolic health through changes in the composition and/or function of the
      gut microbiome. OBJECTIVES: The primary aim of this study was to determine
      whether elevated TRAP exposure was correlated with gut bacterial taxa in
      overweight and obese adolescents from the Meta-AIR (Metabolic and Asthma
      Incidence Research) study. The secondary aim was to examine whether gut microbial
      taxa correlated with TRAP were also correlated with risk factors for type 2
      diabetes (e.g., fasting glucose levels). We additionally explored whether
      correlations between TRAP and these metabolic risk factors could be explained by
      the relative abundance of these taxa. METHODS: Participants (17-19 years; n=43)
      were enrolled between 2014 and 2016 from Southern California. The CALINE4 line
      dispersion model was used to model prior year residential concentrations of
      nitrogen oxides (NOx) as a marker of traffic emissions. The relative abundance of
      fecal microbiota was characterized by 16S rRNA sequencing and spearman partial
      correlations were examined after adjusting for body fat percent. RESULTS: Freeway
      TRAP was correlated with decreased Bacteroidaceae (r=-0.48; p=0.001) and
      increased Coriobacteriaceae (r=0.48; p<0.001). These same taxa were correlated
      with fasting glucose levels, including Bacteroidaceae (r=-0.34; p=0.04) and
      Coriobacteriaceae (r=0.41; p<0.01). Further, freeway TRAP was positively
      correlated fasting glucose (r=0.45; p=0.004) and Bacteroidaceae and
      Coriobacteriaceae explained 24% and 29% of the correlation between TRAP and
      fasting glucose levels. CONCLUSIONS: Increased TRAP exposure was correlated with
      gut microbial taxa and fasting glucose levels. Gut microbial taxa that were
      correlated with TRAP partially explained the correlation between TRAP and fasting
      glucose levels. These results suggest that exposure to air pollutants may
      negatively impact metabolic health via alterations in the gut microbiota.

PMID- 29220802
TI  - Conducting polymer-based electrochemical biosensors for neurotransmitters: A
      review.
AB  - Neurotransmitters are important biochemical molecules that control behavioral and
      physiological functions in central and peripheral nervous system. Therefore, the
      analysis of neurotransmitters in biological samples has a great clinical and
      pharmaceutical importance. To date, various methods have been developed for their
      assay. Of the various methods, the electrochemical sensors demonstrated the
      potential of being robust, selective, sensitive, and real time measurements.
      Recently, conducting polymers (CPs) and their composites have been widely
      employed in the fabrication of various electrochemical sensors for the
      determination of neurotransmitters. Hence, this review presents a brief
      introduction to the electrochemical biosensors, with the detailed discussion on
      recent trends in the development and applications of electrochemical
      neurotransmitter sensors based on CPs and their composites. The review covers the
      sensing principle of prime neurotransmitters, including glutamate, aspartate,
      tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline,
      acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the
      combination with other analytical techniques was also highlighted. Detection
      challenges and future prospective of the neurotransmitter sensors were discussed
      for the development of biomedical and healthcare applications.

PMID- 29220803
TI  - A single-cell analysis platform for electrochemiluminescent detection of
      platelets adhesion to endothelial cells based on Au@DL-ZnCQDs nanoprobes.
AB  - A novel single-cell analysis platform (SCA) was developed for the investigation
      of platelets adhesion to single human umbilical vein endothelial cell (HUVEC) via
      using the adhesion molecule (E-selectin) on the damaged HUVEC as the marker site,
      and integrating electrochemiluminescence (ECL) with the ultrasensitive Au@DL
      ZnCQDs nanoprobes. The Au@DL-ZnCQDs nanocomposite, a kind of double layer zinc
      coadsorbed carbon quantum dot (ZnCQDs) core-shell nanoprobe, was firstly
      constructed by using gold nanoparticles (AuNPs) as the core to load with ZnCQDs
      and then the citrate-modified silver nanoparticles (AgNPs) as the bridge to link
      AuNPs-ZnCQDs with ZnCQDs to form the core-shell with double layer ZnCQDs (DL
      ZnCQDs) nanoprobe, revealed a 10-fold signal amplification. The H2O2-induced
      oxidative damage HUVECs were utilized as the cellular model on which anti-E
      selectin functionalized nanoprobes specially recognized E-selectin, the SCA
      showed that the ECL signals decreased with platelets adhesion to single HUVEC.
      The proposed SCA could effectively and dynamically monitor the adhesion between
      single HUVEC and platelets in the absence and presence of collagen activation,
      moreover, be able to quantitatively detect the number of platelets adhesion to
      single HUVEC, and show a good analytical performance with linear range from 1 to
      15 platelets. In contrast, the HUVEC was down-regulated the expression of
      adhesion molecules by treating with quercetin inhibitor, and the SCA also
      exhibited the feasibility for analysis of platelets adhesion to single HUVEC.
      Therefore, the single-cell analysis platform provided a novel and promising
      protocol for analysis of the single intercellular adhesion, and it will be
      beneficial to elucidate the pathogenesis of cardiovascular diseases.

PMID- 29220805
TI  - Processing of wet Kinnow mandarin (Citrus reticulata) fruit waste into novel
      Bronsted acidic ionic liquids and their application in hydrolysis of sucrose.
AB  - In citrus processing industries, where up to 60% of the whole fruit is discarded,
      generates citrus waste (peel, seeds, membrane, and pulp) on a massive scale. The
      waste does not currently have high-value applications, instead the majority is
      disposed of or pelletized for animal feed. Therefore, a concise and efficacious
      protocol for processing of Kinnow mandarin (Citrus reticulata) fruit waste to
      numerous novel Bronsted acidic ionic liquids (3a-k) have been developed. BAILs
      were characterized using spectroscopic techniques (FT-IR and NMR). Water
      immiscibility of ILs 3a, 3g and 3h, a property never observed with sulfonic acid
      ILs, allowed the catalytic application of BAIL 3a in hydrolysis of sucrose/table
      sugar, giving a mixture of d-glucose and d-fructose in excellent yields. The
      ionic liquid could be recycled for >3 times without significant loss of activity.

PMID- 29220804
TI  - Graphene and Au NPs co-mediated enzymatic silver deposition for the
      ultrasensitive electrochemical detection of cholesterol.
AB  - Cholesterol is an essential ingredient in mammals, and serum cholesterol is a
      major component of atherosclerotic plaques. The level of cholesterol in human
      serum has become an important index for clinical diagnosis and prevention of
      cardiovascular disease. In this paper, a simple and ultrasensitive cholesterol
      biosensor based on graphene oxide (GO) and gold nanoparticles (Au NPs) co
      mediated enzymatic silver deposition was designed by immobilizing cholesterol
      oxidase (CHOD), cholesterol esterase (CHER) and GO onto the surface of Au NPs
      modified screen-printed carbon electrode (SPE). Under the synergistic effect of
      CHER, CHOD and GO, the cholesterol was hydrolyzed to generate hydrogen peroxide,
      which can reduce the silver (Ag) ions in the solution to metallic Ag which
      deposited on the surface of Au NPs modified SPE. The ultrasensitive detection of
      cholesterol was achieved by anodic stripping voltammetry measurement of the
      enzymatically deposited Ag. Under optimal conditions, the anodic stripping peak
      current of Ag increased with the increasing cholesterol concentration in the
      range from 0.01MUg/mL to 5000MUg/mL with a limit of detection of 0.001MUg/mL (S/N
      = 3). In addition, the ultrasensitive cholesterol biosensor exhibited higher
      specificity, acceptable reproducibility and excellent recoveries for cholesterol
      detection.

PMID- 29220807
TI  - Characterization of leaf waste based biochar for cost effective hydrogen sulphide
      removal from biogas.
AB  - Installation of decentralized units for biogas production along with indigenous
      upgradation systems can be an effective approach to meet growing energy demands
      of the rural population. Therefore, readily available leaf waste was used to
      prepare biochar at different temperatures and employed for H2S removal from
      biogas produced via anaerobic digestion plant. It is found that biochar prepared
      via carbonization of leaf waste at 400  degrees C effectively removes 84.2% H2S
      (from 1254 ppm to 201 ppm) from raw biogas for 25 min in a continuous adsorption
      tower. Subsequently, leaf waste biochar compositional, textural and morphological
      properties before and after H2S adsorption have been analyzed using proximate
      analysis, CHNS, BET surface area, FTIR, XRD, and SEM-EDX. It is found that BET
      surface area, pore size, and textural properties of leaf waste biochar plays a
      crucial role in H2S removal from the biogas.

PMID- 29220806
TI  - Enhanced bioremediation of 4-nonylphenol and cadmium co-contaminated sediment by
      composting with Phanerochaete chrysosporium inocula.
AB  - Composting is identified as an effective approach for solid waste disposal. The
      bioremediation of 4-nonylphenol (4NP) and cadmium (Cd) co-contaminated sediment
      was investigated by composting with Phanerochaete chrysosporium (P.
      chrysosporium) inocula. P. chrysosporium inocula and proper C/N ratios (25.51)
      accelerated the composting process accompanied with faster total organic carbon
      loss, 4NP degradation and Cd passivation. Microbiological analysis demonstrated
      that elevated activities of lignocellulolytic enzymes and sediment enzymes was
      conducive to organic chemical transformation. Bacterial community diversity
      results illustrated that Firmicutes and Proteobacteria were predominant species
      during the whole composting process. Aerobic cellulolytic bacteria and organic
      degrading species played significant roles. Toxicity characteristic leaching
      procedure (TCLP) extraction and germination indices results indicated the
      efficient detoxification of 4NP and Cd co-contaminated sediment after 120 days of
      composting. Overall, results demonstrated that P. chrysosporium enhanced
      composting was available for the bioremediation of 4NP and Cd co-contaminated
      sediment.

PMID- 29220808
TI  - Metabolic engineering of carbon overflow metabolism of Bacillus subtilis for
      improved N-acetyl-glucosamine production.
AB  - Bacillus subtilis is widely used as cell factories for the production of
      important industrial biochemicals. Although many studies have demonstrated the
      effects of organic acidic byproducts, such as acetate, on microbial fermentation,
      little is known about the effects of blocking the neutral byproduct overflow,
      such as acetoin, on bioproduction. In this study, we focused on the influences of
      modulating overflow metabolism on the production of N-acetyl-d-glucosamine
      (GlcNAc) in engineered B. subtilis. We found that acetoin overflow competes with
      GlcNAc production, and blocking acetoin overflow increased GlcNAc titer and yield
      by 1.38- and 1.39-fold, reaching 48.9 g/L and 0.32 g GlcNAc/g glucose,
      respectively. Further blocking acetate overflow inhibited cell growth and GlcNAc
      production may be induced by inhibiting glucose uptake. Taken together, our
      results show that blocking acetoin overflow is a promising strategy for enhancing
      GlcNAc production. The strategies developed in this work may be useful for
      engineering strains of B. subtilis for producing other important biochemicals.

PMID- 29220809
TI  - Biodegradation and detoxification of Direct Black G textile dye by a newly
      isolated thermophilic microflora.
AB  - The biodegradation and detoxification of azo dye - Direct Black G (DBG) with a
      newly isolated thermophilic microflora was investigated in the present study. It
      was found this microflora can decolorize DBG at a wide range of pH from 5 to 10,
      and grow well under high concentration of dye (600 mg.L-1) and salinity (50 g.L
      1). Its decolorization ratio could reach 97% with 8 h of incubation at optimal
      conditions. The induction of laccase, manganese peroxidase, lignin peroxidase and
      azoreductase suggests their synergetic involvements in the degradation process of
      DBG. In addition, the phytotoxicity analysis indicated the thermophilic
      microflora converted toxic dye DBG into low toxicity metabolites. PCR-DGGE
      analysis revealed that there are nine different bacteria presented in this
      microflora. Furthermore, a new degradation pathway of DBG degradation by this
      microflora was proposed based on the intermediates identified by LC-ESI-MS/MS.

PMID- 29220810
TI  - Simultaneous efficient removal of oxyfluorfen with electricity generation in a
      microbial fuel cell and its microbial community analysis.
AB  - The performance of a microbial fuel cell (MFC) to degrade oxyfluorfen was
      investigated. Approximately 77% of 50 mg/L oxyfluorfen was degraded within 24 h
      by anodic biofilm. The temperature, pH, and initial oxyfluorfen concentration had
      a significant effect on oxyfluorfen degrading, and a maximum degradation rate of
      94.95% could theoretically be achieved at 31.96  degrees C, a pH of 7.65, and an
      initial oxyfluorfen concentration of 120.05 mg/L. Oxyfluorfen was further
      catabolized through various microbial metabolism pathways. Moreover, the anodic
      biofilm exhibited multiple catabolic capacities to 4-nitrophenol,
      chloramphenicol, pyraclostrobin, and sulfamethoxazole. Microbial community
      analysis indicated that functional bacteria Arcobacter, Acinetobacter,
      Azospirillum, Azonexus, and Comamonas were the predominant genera in the anodic
      biofilm. In terms of the efficient removal of various organic compounds and
      energy recovery, the MFC seemed to be a promising approach for the treatment of
      environmental contaminants.

PMID- 29220811
TI  - Synergistic effect of the enzyme complexes comprising agarase, carrageenase and
      neoagarobiose hydrolase on degradation of the red algae.
AB  - In the practice of converting red algae biomass into biofuel or valuable
      biomaterials, the critical step is the decomposition process of the agarose to
      give fermentable monomeric sugars. In this study, we selected three enzymes such
      as agarase, carrageenase and neoagarobiose hydrolase to inducible the
      simultaneous hydrolysis of the major substrates such as agar and carrageenan
      constituting the pretreated red algae, and expressed the chimeric enzymes and
      formed a complexes through optimization of addition ratio. As a result,
      hydrolysis by enzyme complexes showed a maximum sugar release of 679 mg L-1 with
      67.9% saccharification yield from G. verrucosa natural substrate. The difference
      in the reducing sugar by the enzyme complexes was 3.6-fold higher than that of
      the monomer enzyme (cAgaB yield 188.6 mg L-1). The synergistic effect of
      producing sugars from red algae biomass through these enzyme complexes can be a
      very important biological tools aimed at bioenergy production.

PMID- 29220812
TI  - Bioethanol potential of Eucalyptus obliqua sawdust using gamma-valerolactone
      fractionation.
AB  - Optimisation of conditions for gamma-valerolactone (GVL) pretreatment of
      Australian eucalyptus sawdust for high cellulose biomass and bioethanol
      production was demonstrated. Pretreatment parameters investigated included GVL
      concentrations of 35-50% w/w, temperatures of 120-180  degrees C and reaction
      durations of 0.5-2.0 h. Optimum conditions were determined using the response
      surface method (RSM) and central composite face-centred design. Cellulose content
      increased from 39.9% to a maximum of 89.3% w/w using treatments with 50% GVL at
      156  degrees C for 0.5 h. Temperature had the most significant effect (RSM p <
      .05) on cellulose content of residual biomass and reducing operational duration
      of < 0.5 h may be viable according to RSM. PSSF fermentations of optimised
      pretreated eucalyptus sawdust produced up to 94% theoretical ethanol yield, which
      corresponded to approximately 181 kg of ethanol per dry ton of eucalyptus
      sawdust. The compositions of both the residual biomass and pretreatment liquors
      show that GVL pretreatment is a promising solvent for lignocellulosic
      biorefining.

PMID- 29220813
TI  - Biotransformation and inhibition effects of hexachlorocyclohexanes during biogas
      production from contaminated biomass characterized by isotope fractionation
      concepts.
AB  - Hexachlorocyclohexane (HCH) production for pesticides was banned by Stockholm
      Convention (2009) due to its harmful and adverse effects on the environment.
      Despite this measure, many areas contaminated with former HCH production-waste
      products still require management. As a potential solution contributing to clean
      up of these sites, anaerobic digestion (AD) of pesticide-contaminated biomass to
      produce biogas is a promising strategy. High pesticide concentrations, however,
      may inhibit biogas production. Therefore, laboratory-scale batch reactors were
      set up to investigate biogas reactor performance in presence of HCH. Inhibitory
      effects on biogas yield was observed with concentrations of HCH >= 150 mg/L.
      Carbon isotope composition of methane (delta13CCH4) showed significant
      fluctuation after an inhibition phase, indicating that HCH toxicity can affect
      the activity of acetoclastic methanogens. Furthermore, combined results of
      metabolites and carbon isotope fractionation factors (epsilonc) demonstrated that
      alpha- and gamma-HCH can be degraded to chlorobenzene and benzene via anaerobic
      reductive dechlorination.

PMID- 29220814
TI  - Butyric acid production from lignocellulosic biomass hydrolysates by engineered
      Clostridium tyrobutyricum overexpressing Class I heat shock protein GroESL.
AB  - Lignocellulosic biomass is the most abundant and renewable substrate for
      biological fermentation, but the inhibitors present in the lignocellulosic
      hydrolysates could severely inhibit the cell growth and productivity of
      industrial strains. This study confirmed that overexpressing of native groESL in
      Clostridium tyrobutyricum could significantly improve its tolerance to
      lignocellulosic hydrolysate-derived inhibitors, especially for phenolic
      compounds. Consequently, ATCC 25755/groESL showed a better performance in butyric
      acid fermentation with hydrolysates of corn cob, corn straw, rice straw, wheat
      straw, soybean hull and soybean straw, respectively. When corn straw and rice
      straw hydrolysates, which showed strong toxicity to C. tyrobutyricum, were used
      as the substrates, 29.6 g/L and 30.1 g/L butyric acid were obtained in batch
      fermentation, increased by 26.5% and 19.4% as compared with the wild-type strain,
      respectively. And more importantly, the butyric acid productivity reached 0.31
      g/L.h (vs. 0.20-0.21 g/L.h for the wild-type strain) due to the shortened lag
      phase.

PMID- 29220815
TI  - Influence of fermentation liquid from waste activated sludge on anoxic/oxic-
      membrane bioreactor performance: Nitrogen removal, membrane fouling and microbial
      community.
AB  - In order to investigate effects of waste activated sludge (WAS) fermentation
      liquid on anoxic/oxic- membrane bioreactor (A/O-MBR), two A/O-MBRs with and
      without WAS fermentation liquid addition were operated in parallel. Results show
      that addition of WAS fermentation liquid clearly improved denitrification
      efficiency without deterioration of nitrification, while severe membrane fouling
      occurred. WAS fermentation liquid resulted in an elevated production of proteins
      and humic acids in bound extracellular polymeric substance (EPS) and release of
      organic matter with high MW fractions in soluble microbial product (SMP) and
      loosely bound EPS (LB-EPS). Measurement of deposition rate and fluid structure
      confirmed increased fouling potential of SMP and LB-EPS. gamma-Proteobacteria and
      Ferruginibacter, which can secrete and export EPS, were also found to be abundant
      in the MBR with WAS fermentation liquid. It is implied that when WAS fermentation
      liquid was applied, some operational steps to control membrane fouling should be
      employed.

PMID- 29220816
TI  - FTIR and Raman spectroscopic studies of selenium nanoparticles synthesised by the
      bacterium Azospirillum thiophilum.
AB  - Vibrational (Fourier transform infrared (FTIR) and Raman) spectroscopic
      techniques can provide unique molecular-level information on the structural and
      compositional characteristics of complicated biological objects. Thus, their
      applications in microbiology and related fields are steadily increasing. In this
      communication, biogenic selenium nanoparticles (Se NPs) were obtained via
      selenite (SeO32-) reduction by the bacterium Azospirillum thiophilum (strain VKM
      B-2513) for the first time, using an original methodology for obtaining
      extracellular NPs. Dynamic light scattering (DLS) and transmission electron
      microscopy (TEM) showed the Se NPs to have average diameters within 160-250nm;
      their zeta potential was measured to be minus 18.5mV. Transmission FTIR spectra
      of the Se NPs separated from bacterial cells showed typical proteinacious,
      polysaccharide and lipid-related bands, in line with TEM data showing a thin
      layer covering the Se NPs surface. Raman spectra of dried Se NPs layer in the low
      frequency region (under 500cm-1 down to 150cm-1) showed a single very strong band
      with a maximum at 250cm-1 which, in line with its increased width (ca. 30cm-1 at
      half intensity), can be attributed to amorphous elementary Se. Thus, a
      combination of FTIR and Raman spectroscopic approaches is highly informative in
      non-destructive analysis of structural and compositional properties of biogenic
      Se NPs.

PMID- 29220817
TI  - Infrared spectroscopy of flavones and flavonols. Reexamination of the hydroxyl
      and carbonyl vibrations in relation to the interactions of flavonoids with
      membrane lipids.
AB  - Detailed vibrational assignments for twelve flavonoids (seven flavones (flavone,
      3- and 5-hydroxyflavone, chrysin, apigenin, fisetin and luteolin) and five
      flavonols (galangin, kaempferol, quercetin, morin and myricetin)) have been made
      based on own and reported experimental data and calculations at the B3LYP/6
      31+G(d,p) level of theory. All the molecules are treated in a uniform way by
      using the same set of redundancy-free set of internal coordinates. A generalized
      harmonic mode mixing is used to corroborate the vibrational characteristics of
      this important class of molecules. Each flavonoid molecule can be treated from
      the vibrational point of view as made of relatively weakly coupled chromone and
      phenyl part. It has been shown that the strongest band around 1600cm-1 need not
      be attributable to the CO stretching. The way the vibrations of any of the
      hydroxyl groups are mixed with ring vibrations and vibrations of other
      neighboring hydroxyl groups is rather involved. This imposes severe limitations
      on any attempt to describe normal modes of a flavonol in terms of hydroxyl or
      carbonyl group vibrations. The role of water molecules in the appearance of
      flavonoid IR spectra is emphasized. Knowing for the great affinity of phosphate
      groups in lipids towards water, the immediate consequence is a reasonable
      assumption that flavonoid lipid interactions is mediated by water.

PMID- 29220818
TI  - Reuse of sustainable materials for xylenol orange dye and copper (II) ion
      ammoniacal removal.
AB  - Water pollution caused by heavy metals and organic compounds is an environmental
      problem with negative impact, making the restoration of water quality a priority.
      In this paper, the adsorption of xylenol orange dye (XO) on vitreous tuff mineral
      (VT) was studied. It was established that the adsorption capacity of VT was 45.17
      mg/g. The removal was carried out by interactions between active sites on the
      surface of the material and the functional groups of the dye. The solid waste
      obtained from this process (VTXO) was reused as adsorbent material for Cu removal
      in the form of the complex Cu-NH3 because this process was done in an ammoniacal
      medium. It was found that the adsorption capacity of this new material was 33.09
      mg/g. In a previous research, VT mineral was used to remove crystal violet (CV)
      instead of XO. The solid waste of this last process (VTCV) was also applied for
      Cu-NH3 removal, in order to compare the adsorption capacity of VT after the
      adsorption of two different kinds of dyes. The adsorption capacity of VTXO was
      lower than that of VTCV (71.23 mg/g). In both processes, adsorption kinetic was
      well described by a chemical adsorption onto a heterogeneous surface. The
      equilibrium time for XO removal was 50 min and 80 min for Cu-NH3. The
      experimental design stated that the maximum adsorption capacity was reached when
      the initial concentration was 6400 mg/L and the solid-liquid ratio was 10 g/L.
      The system that requires the least amount of adsorbent was the counter flow
      batch. Finally, it was possible to estimate the behavior of the system on a
      higher scale. This research provides an efficient and economical alternative to
      treat water contaminated with dyes and cooper in an ammoniacal medium using the
      same material in both processes, one after the other.

PMID- 29220819
TI  - Fluoride removal from water using a magnesia-pullulan composite in a continuous
      fixed-bed column.
AB  - A magnesia-pullulan composite (MgOP) was previously shown to effectively remove
      fluoride from water. In the present study, a continuous fixed-bed column was used
      to examine the application of the composite at an industrial scale. The
      influencing parameters included bed mass (4.0, 6.0 and 8.0 g), influent flow rate
      (8, 16 and 32 mL/min), inlet fluoride concentration (5, 10 and 20 mg/L), reaction
      temperature (20, 30 and 40  degrees C), influent pH (4, 7 and 10) and other
      existing anions (HCO3-, SO42-, Cl- and NO3-), through which the breakthrough
      curves could be depicted for the experimental data analysis. The results
      indicated that MgOP is promising for fluoride removal with a defluoridation
      capacity of 16.6 mg/g at the bed mass of 6.0 g, influent flow rate of 16 mL/min
      and inlet fluoride concentration of 10 mg/L. The dynamics of the fluoride
      adsorption process were modeled using the Thomas and Yan models, in which the Yan
      model presented better predictions for the breakthrough curves than the Thomas
      model. Moreover, the concentration of magnesium in the effluent was monitored to
      determine Mg stability in the MgOP composite. Results indicated the effluent
      concentration of Mg2+ ions could be kept at a safe level. Calcination of fluoride
      loaded MgOP effectively regenerated the material.

PMID- 29220820
TI  - Application of an in-situ soil sampler for assessing subsurface biogeochemical
      dynamics in a diesel-contaminated coastal site during soil flushing operations.
AB  - Subsurface biogeochemistry and contaminant dynamics during the remediation of
      diesel-contamination by in-situ soil flushing were investigated at a site located
      in a coastal region. An in-situ sampler containing diesel-contaminated soils
      separated into two size fractions (<0.063- and <2-mm) was utilized in two
      monitoring wells: DH1 (located close to the injection and extraction wells for in
      situ soil flushing) and DH2 (located beyond sheet piles placed to block the
      transport of leaked diesel). Total petroleum hydrocarbon (TPH) concentrations and
      biogeochemical properties were monitored both in soil and groundwater for six
      months. A shift occurred in the groundwater type from Ca-HCO3 to Na-Cl due to
      seawater intrusion during intense pumping, while the concentrations of Ni, Cu,
      Co, V, Cr, and Se increased substantially following surfactant (TWEEN 80)
      injection. The in-situ sampler with fine particles was more sensitive to
      variations in conditions during the remedial soil flushing process. In both
      wells, soil TPH concentrations in the <0.063-mm fraction were much higher than
      those in the <2-mm fraction. Increases in soil TPH in DH1 were consistent with
      the expected outcomes following well pumping and surfactant injection used to
      enhance TPH extraction. However, the number of diesel-degrading microorganisms
      decreased after surfactant injection. 16S-rRNA gene-based analysis also showed
      that the community composition and diversity depended on both particle size and
      diesel contamination. The multidisciplinary approach to the contaminated site
      assessments showed that soil flushing with surfactant enhanced diesel extraction,
      but negatively impacted in-situ diesel biodegradation as well as groundwater
      quality. The results also suggest that the in-situ sampler can be an effective
      monitoring tool for subsurface biogeochemistry as well as contaminant dynamics.

PMID- 29220821
TI  - Predictive capabilities of various constitutive models for arterial tissue.
AB  - INTRODUCTION: Aim of this study is to validate some constitutive models by
      assessing their capabilities in describing and predicting uniaxial and biaxial
      behavior of porcine aortic tissue. METHODS: 14 samples from porcine aortas were
      used to perform 2 uniaxial and 5 biaxial tensile tests. Transversal strains were
      furthermore stored for uniaxial data. The experimental data were fitted by four
      constitutive models: Holzapfel-Gasser-Ogden model (HGO), model based on
      generalized structure tensor (GST), Four-Fiber-Family model (FFF) and Microfiber
      model. Fitting was performed to uniaxial and biaxial data sets separately and
      descriptive capabilities of the models were compared. Their predictive
      capabilities were assessed in two ways. Firstly each model was fitted to biaxial
      data and its accuracy (in term of R2 and NRMSE) in prediction of both uniaxial
      responses was evaluated. Then this procedure was performed conversely: each model
      was fitted to both uniaxial tests and its accuracy in prediction of 5 biaxial
      responses was observed. RESULTS: Descriptive capabilities of all models were
      excellent. In predicting uniaxial response from biaxial data, microfiber model
      was the most accurate while the other models showed also reasonable accuracy.
      Microfiber and FFF models were capable to reasonably predict biaxial responses
      from uniaxial data while HGO and GST models failed completely in this task.
      CONCLUSIONS: HGO and GST models are not capable to predict biaxial arterial wall
      behavior while FFF model is the most robust of the investigated constitutive
      models. Knowledge of transversal strains in uniaxial tests improves robustness of
      constitutive models.

PMID- 29220822
TI  - Fatigue and biological properties of Ti-6Al-4V ELI cellular structures with
      variously arranged cubic cells made by selective laser melting.
AB  - Traditional implants made of bulk titanium are much stiffer than human bone and
      this mismatch can induce stress shielding. Although more complex to produce and
      with less predictable properties compared to bulk implants, implants with a
      highly porous structure can be produced to match the bone stiffness and at the
      same time favor bone ingrowth and regeneration. This paper presents the results
      of the mechanical and dimensional characterization of different regular cubic
      open-cell cellular structures produced by Selective Laser Melting (SLM) of
      Ti6Al4V alloy, all with the same nominal elastic modulus of 3GPa that matches
      that of human trabecular bone. The main objective of this research was to
      determine which structure has the best fatigue resistance through fully reversed
      fatigue tests on cellular specimens. The quality of the manufacturing process and
      the discrepancy between the actual measured cell parameters and the nominal CAD
      values were assessed through an extensive metrological analysis. The results of
      the metrological assessment allowed us to discuss the effect of manufacturing
      defects (porosity, surface roughness and geometrical inaccuracies) on the
      mechanical properties. Half of the specimens was subjected to a stress relief
      thermal treatment while the other half to Hot Isostatic Pressing (HIP), and we
      compared the effect of the treatments on porosity and on the mechanical
      properties. Fatigue strength seems to be highly dependent on the surface
      irregularities and notches introduced during the manufacturing process. In fully
      reversed fatigue tests, the high performances of stretching dominated structures
      compared to bending dominated structures are not found. In fact, with thicker
      struts, such structures proved to be more resistant, even if bending actions were
      present.

PMID- 29220824
TI  - Extensive geographical and social structure in the paternal lineages of Saudi
      Arabia revealed by analysis of 27 Y-STRs.
AB  - Saudi Arabia's indigenous population is organized into patrilineal descent
      groups, but to date, little has been done to characterize its population
      structure, in particular with respect to the male-specific region of the Y
      chromosome. We have used the 27-STR Yfiler(r) Plus kit to generate haplotypes in
      597 unrelated Saudi males, classified into five geographical regions (North,
      South, Central, East and West). Overall, Yfiler(r) Plus provides a good
      discrimination capacity of 95.3%, but this is greatly reduced (74.7%) when
      considering the reduced Yfiler(r) set of 17 Y-STRs, justifying the use of the
      expanded set of markers in this population. Comparison of the five geographical
      divisions reveals striking differences, with low diversity and similar haplotype
      spectra in the Central and Northern regions, and high diversity and similar
      haplotype spectra in the East and West. These patterns likely reflect the
      geographical isolation of the desert heartland of the peninsula, and the
      proximity to the sea of the Eastern and Western areas, and consequent historical
      immigration. We predicted haplogroups from Y-STR haplotypes, testing the
      performance of prediction by using a large independent set of Saudi Arabian Y-STR
      + Y-SNP data. Prediction indicated predominance (71%) of haplogroup J1, which was
      significantly more common in Central, Northern and Southern groups than in East
      and West, and formed a star-like expansion cluster in a median-joining network
      with an estimated age of ~2800 years. Most of our 597 participants were sampled
      within Saudi Arabia itself, but ~16% were sampled in the UK. Despite matching
      these two groups by home sub-region, we observed significant differences in
      haplotype and predicted haplogroup constitutions overall, and for most sub
      regions individually. This suggests social structure influencing the probability
      of leaving Saudi Arabia, correlated with different Y-chromosome compositions. The
      UK-recruited sample is an inappropriate proxy for Saudi Arabia generally, and
      caution is needed when considering expatriate groups as representative of country
      of origin. Our study shows the importance of geographical and social structuring
      that may affect the utility of forensic databases and the interpretation of Y-STR
      profiles.

PMID- 29220825
TI  - Effects of nutritional education on weight change and metabolic abnormalities
      among patients with schizophrenia in Japan: A randomized controlled trial.
AB  - OBJECTIVE: Patients with schizophrenia have a higher prevalence of metabolic
      syndrome (MetS) than the general population. Minimizing weight gain and metabolic
      abnormalities in a population with an already high prevalence of obesity is of
      clinical and social importance. This randomized controlled trial investigated the
      effect of monthly nutritional education on weight change and metabolic
      abnormalities among patients with schizophrenia in Japan. METHODS: From July 2014
      to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of
      schizophrenia or schizoaffective disorder. Participants were randomly assigned to
      a standard care (A), doctor's weight loss advice (B), or an individual
      nutritional education group (C) for 12 months. The prevalence of MetS and body
      weight were measured at baseline and 12 months. RESULTS: After the 12-month
      treatment, 189 patients were evaluated, and the prevalence of MetS based on the
      ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%,
      respectively. Group C showed increased weight loss (3.2 +/- 4.5 kg) over the 12
      month study period, and the change in weight differed significantly from that of
      group A; additionally, 26.2% of the participants in group C lost 7% or more of
      their initial weight, compared with 8.2% of those in group A. CONCLUSION:
      Individual nutrition education provided by a dietitian was highly successful in
      reducing obesity in patients with schizophrenia and could be the first choice to
      address both weight gain and metabolic abnormalities induced by antipsychotic
      medications.

PMID- 29220823
TI  - Patterns of progressive atrophy vary with age in Alzheimer's disease patients.
AB  - Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a
      key modifier of disease presentation and progression. Here, we investigate how
      longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI)
      and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans
      from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal
      volume change were obtained and aligned across subjects. Local volume change was
      then modeled in terms of diagnostic group and an interaction between group and
      age, adjusted for total intracranial volume, white-matter hyperintensity volume,
      and apolipoprotein E genotype. Results were significant at p < 0.05 with family
      wise error correction for multiple comparisons. An age-by-group interaction
      revealed that younger AD patients had significantly faster atrophy rates in the
      bilateral precuneus, parietal, and superior temporal lobes. These results suggest
      younger AD patients have predominantly posterior progressive atrophy, unexplained
      by white-matter hyperintensity, apolipoprotein E, or total intracranial volume.
      Clinical trials may benefit from adapting outcome measures for patient groups
      with lower average ages, to capture progressive atrophy in posterior cortices.

PMID- 29220826
TI  - Time distortion when users at-risk for social media addiction engage in non
      social media tasks.
AB  - BACKGROUND: There is a growing concern over the addictiveness of Social Media
      use. Additional representative indicators of impaired control are needed in order
      to distinguish presumed social media addiction from normal use. AIMS: (1) To
      examine the existence of time distortion during non-social media use tasks that
      involve social media cues among those who may be considered at-risk for social
      media addiction. (2) To examine the usefulness of this distortion for at-risk vs.
      low/no-risk classification. METHOD: We used a task that prevented Facebook use
      and invoked Facebook reflections (survey on self-control strategies) and
      subsequently measured estimated vs. actual task completion time. We captured the
      level of addiction using the Bergen Facebook Addiction Scale in the survey, and
      we used a common cutoff criterion to classify people as at-risk vs. low/no-risk
      of Facebook addiction. RESULTS: The at-risk group presented significant upward
      time estimate bias and the low/no-risk group presented significant downward time
      estimate bias. The bias was positively correlated with Facebook addiction scores.
      It was efficacious, especially when combined with self-reported estimates of
      extent of Facebook use, in classifying people to the two categories. CONCLUSIONS:
      Our study points to a novel, easy to obtain, and useful marker of at-risk for
      social media addiction, which may be considered for inclusion in diagnosis tools
      and procedures.

PMID- 29220827
TI  - Exploring Drivers of Forest Degradation and Fragmentation in Sudan: The Case of
      Erawashda Forest and its Surrounding Community.
AB  - Sudan is a hot spot for forest degradation. Efforts to maintain what remains of
      its forests should be of the highest priority. However, precise information on
      its forests' current state is very limited. Therefore, in order to effectively
      intervene in support of existing resources, it is important to have a better
      understanding of processes taking place in the country and impacting those
      resources. The objectives of this study are to quantify the consequences of land
      use and land cover (LULC) changes on forest degradation and fragmentation and to
      analyze the anthropogenic factors causing it, taking Erawashda Forest, eastern
      Sudan, as an example. The study utilized a series of Landsat imageries, field
      surveys and interviews with informants to analyze the decrease in forest cover.
      The years between 1973 and 2015 saw a 16.9% and 5.4% increase in bare land and
      large-scale mechanized agriculture respectively. During the same period there was
      a 37% decrease in dense forest cover and a 20% increase in light forest cover.
      The trajectory analysis showed that all LULC categories are subjected to very
      rapid changes from one class to another throughout the period of the study and
      the most dynamic class is light forest cover. Computed fragmentation indices
      showed that large core is the dominant category. Key informants identified the
      main factors of degradation and fragmentation as the expansion of mechanized rain
      fed agriculture, felling of trees and wood cutting, bad grazing activities, and
      construction of infrastructure. Information garnered from this study can provide
      a good basis for forest rehabilitation programs and can also be used for
      developing proper management plans that take into account the needs of the
      communities utilizing the forest.

PMID- 29220828
TI  - Prediction of Radiation Esophagitis in Non-Small Cell Lung Cancer Using Clinical
      Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels.
AB  - Radiation esophagitis (RE) is a common adverse event associated with radiotherapy
      for non-small cell lung cancer (NSCLC). While plasma cytokine levels have been
      correlated with other forms of radiation-induced toxicity, their association with
      RE has been less well studied. We analyzed data from 126 patients treated on 4
      prospective clinical trials. Logistic regression models based on combinations of
      dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent
      uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30
      cytokines were developed. Cross-validated estimates of area under the receiver
      operating characteristic curve (AUC) and log likelihood were used to assess
      prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of
      0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the
      AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct
      associations with RE and as potential interactions with the dose-esophagitis
      association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD
      correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy,
      respectively. Female gender was associated with a higher risk of RE, with ORs of
      1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was
      associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in
      the D2cc and gEUD models, respectively. Combining clinical with dosimetric
      factors but not pretreatment cytokine levels yielded improved prediction of grade
      3 RE compared to prediction by dose alone. Such multifactorial modeling may prove
      useful in directing radiation treatment planning.

PMID- 29220829
TI  - Decreased Expression of the Polarity Regulatory PAR Complex Predicts Poor
      Prognosis of the Patients with Colorectal Adenocarcinoma.
AB  - Partitioning defective (Par) proteins regulate cell polarity and differentiation.
      Par3, Par6beta, and protein kinase Czeta (PKCzeta), which are PAR complex
      members, have been shown to be associated with oncogenesis and progression.
      Herein, we report the expression pattern and clinical relevance of Par3,
      Par6beta, and PKCzeta in colorectal adenocarcinoma (CRAC). A total of 393 primary
      CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia,
      and 41 nontumor colorectal tissue samples were examined by immunohistochemistry
      and Western blot assays for Par3, Par6beta, and PKCzeta protein expressions. The
      association Par3, Par6beta, and PKCzeta expressions and clinicopathologic
      factors, including patient survival, was evaluated. Primary CRACs and adenomas
      demonstrated higher levels of Par3, Par6beta, and PKCzeta than in nontumor
      colorectal epithelia. The expressions of Par3, Par6beta, and PKCzeta were higher
      in primary CRACs as compared to adenomas or in metastatic CRACs. Among primary
      CRACs, decreased Par3 expression was found to correlate with a high proliferation
      rate and poor histologic differentiation, decreased PKCzeta expression was
      correlated with pathologic TNM stage (I-II vs III-IV) and lymph node metastasis,
      and decreased Par6beta and PKCzeta expressions were correlated with shortened
      overall survivals. In metastatic CRACs, decreased PKCzeta expression was
      correlated with a shortened metastasis-free survival. While increased Par3,
      Par6beta, and PKCzeta expressions were implicated in tumorigenesis, decreased
      expressions of Par3, Par6beta, and PKCzeta were found to be associated with worse
      clinicopathologic factors in CRAC. In particular, the results of our study
      suggest that PKCzeta down-expression is an independent poor prognostic and
      metastatic factor for CRAC.

PMID- 29220831
TI  - Correction: Priming with Recombinant Auxotrophic BCG Expressing HIV-1 Gag, RT and
      Gp120 and Boosting with Recombinant MVA Induces a Robust T Cell Response in Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0071601.].

PMID- 29220830
TI  - Specific capture, recovery and culture of cancer cells using oriented antibody
      modified polystyrene chips coated with agarose film.
AB  - Agarose gel can be used for three dimensional (3D) cell culture because it
      prevents cell attachment. The dried agarose film coated on a culture plate also
      protected cell attachment and allowed 3D growth of cancer cells. We developed an
      efficient method for agarose film coating on an oxygen-plasma treated micropost
      polystyrene chip prepared by an injection molding process. The agarose film was
      modified to maleimide or Ni-NTA groups for covalent or cleavable attachment of
      photoactivatable Fc-specific antibody binding proteins (PFcBPs) via their N
      terminal cysteine residues or 6xHis tag, respectively. The antibodies
      photocrosslinked onto the PFcBP-modified chips specifically captured the target
      cells without nonspecific binding, and the captured cells grew 3D modes on the
      chips. The captured cells on the cleavable antibody-modified chips were easily
      recovered by treatment of commercial trypsin-EDTA solution. Under fluidic
      conditions using an antibody-modified micropost chip, the cells were mainly
      captured on the micropost walls of the chip rather than on the bottom of it. The
      presented method will also be applicable for immobilization of oriented
      antibodies on various microfluidic chips with different structures.

PMID- 29220832
TI  - Correction: Diagnostic Potential of the NMDA Receptor Peptide Assay for Acute
      Ischemic Stroke.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0042362.].

PMID- 29220833
TI  - Correction: Recombinant Yellow Fever Viruses Elicit CD8+ T Cell Responses and
      Protective Immunity against Trypanosoma cruzi.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0059347.].

PMID- 29220834
TI  - Correction: Expired CO2 Levels Indicate Degree of Lung Aeration at Birth.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0070895.].

PMID- 29220835
TI  - Correction: Phrasal Paraphrase Based Question Reformulation for Archived Question
      Retrieval.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0064601.].

PMID- 29220836
TI  - Correction: Lycopene Inhibits NF-kB-Mediated IL-8 Expression and Changes Redox
      and PPARgamma Signalling in Cigarette Smoke-Stimulated Macrophages.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0019652.].

PMID- 29220837
TI  - Correction: Iron Supplementation Decreases Severity of Allergic Inflammation in
      Murine Lung.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0045667.].

PMID- 29220838
TI  - Correction: A Developmental Stage-Specific Switch from DAZL to BOLL Occurs during
      Fetal Oogenesis in Humans, but Not Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0073996.].

PMID- 29220839
TI  - Correction: Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and
      Tuberculosis Co-Infected Adults in South Africa.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0044793.].

PMID- 29220840
TI  - Correction: Methylation State of the EDA Gene Promoter in Chinese X-Linked
      Hypohidrotic Ectodermal Dysplasia Carriers.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0062203.].

PMID- 29220841
TI  - Correction: Bcl-w Enhances Mesenchymal Changes and Invasiveness of Glioblastoma
      Cells by Inducing Nuclear Accumulation of beta-Catenin.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0068030.].

PMID- 29220842
TI  - Correction: Cryopreservation Causes Genetic and Epigenetic Changes in Zebrafish
      Genital Ridges.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0067614.].

PMID- 29220843
TI  - Correction: Efficient Sensing of Infected Cells in Absence of Virus Particles by
      Plasmacytoid Dendritic Cells Is Blocked by the Viral Ribonuclease Erns.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1003412.].

PMID- 29220844
TI  - Correction: Glycolipid Transfer Protein Expression Is Affected by
      Glycosphingolipid Synthesis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0070283.].

PMID- 29220845
TI  - Correction: Deep Vascular Imaging in Wounds by Two-Photon Fluorescence
      Microscopy.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0067559.].

PMID- 29220846
TI  - Correction: Multiple Analyses of G-Protein Coupled Receptor (GPCR) Expression in
      the Development of Gefitinib-Resistance in Transforming Non-Small-Cell Lung
      Cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0044368.].

PMID- 29220847
TI  - Correction: I Should but I Won't: Why Young Children Endorse Norms of Fair
      Sharing but Do Not Follow Them.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0059510.].

PMID- 29220848
TI  - Correction: Pre-Treatment with Amifostine Protects against Cyclophosphamide
      Induced Disruption of Taste in Mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0061607.].

PMID- 29220849
TI  - Correction: A-Methylacyl-CoA Racemase (AMACR) and Prostate-Cancer Risk: A Meta
      Analysis of 4,385 Participants.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0074386.].

PMID- 29220851
TI  - Puestow Procedure for the Management of Pediatric Chronic Pancreatitis.

PMID- 29220852
TI  - Commentary: Controversies in Thrombosis and Hemostasis Part 1-Hematidrosis:
      "Blood, Sweat and Fears" or A "Pigment of Fertile Imaginations?"

PMID- 29220853
TI  - Hematidrosis: A Fascinating Phenomenon-Case Study and Overview of the Literature.

PMID- 29220854
TI  - Inhibitors in Hemophilia A: A Pharmacoeconomic Perspective.
AB  - A discussion of the main pharmacoeconomic issues related to inhibitors in
      hemophilia A cannot be separated from an analysis of the most relevant clinical
      questions. In the field of inhibitors, the clinical evidence includes several
      controversial topics, such as high-titer versus low-titer inhibitors, the
      influence of factor VIII products on inhibitor risk, effectiveness of different
      immune tolerance induction (ITI) treatments, the role of bypassing agents, and
      development of new non-factor-VIII compounds. In terms of pharmacoeconomic data,
      numerous cost estimates have been reported in these fields, but this information
      is strongly influenced by the wide between-country differences in unit costs.
      Quite reliable data are, however, available regarding expenditure for replacement
      therapy in patients without inhibitors, increased lifetime costs caused by high
      titer inhibitors, and cost of pharmacological interventions aimed at eradicating
      inhibitors. As regards the cost-effectiveness ratio, the data on ITI are not
      conclusive; nonetheless, irrespective of the specific treatments employed for
      inducing tolerance, their costs seem to be offset by the subsequent savings in
      the cost per patient. Other issues, such as the cost of low-titer inhibitors in
      patients with hemophilia A and effectiveness of pharmacological interventions
      aimed at eradicating low-titer inhibitors are not supported by sound data and
      will require further research. Finally, although the efficacy and safety profiles
      of novel treatments (e.g., emicizumab, Roche) warrant long-term clinical studies,
      the economic advantages of these new compounds might be very substantial both in
      patients with inhibitors and in those at risk of developing inhibitors.

PMID- 29220856
TI  - Prevalence and Characteristics of Intracranial Hemorrhages in Neonates with
      Hypoxic Ischemic Encephalopathy.
AB  - INTRODUCTION:  The risk factors of intracranial hemorrhages (ICH) in the context
      of neonatal hypoxic ischemic encephalopathy (HIE) and related interventions are
      unclear. OBJECTIVE:  This article examines the prevalence and risk factors
      associated with ICH in neonates with HIE. STUDY DESIGN:  This is a retrospective
      cohort study of neonates with HIE in Southern Alberta. ICH (subdural [SDH],
      subarachnoid [SAH], intraventricular [IVH], intraparenchymal [IPH]) were
      diagnosed by magnetic resonance imaging (MRI). Perinatal and neonatal
      characteristics were examined. Relation of hemorrhages with hypoxic changes on
      MRI and HIE stages were assessed. RESULTS:  Number of HIE patients, n = 157;
      brain MRI was done in 138 infants; median gestation, 40 weeks; and cooled = 103
      (66%). Prevalence of SDH, IPH, IVH, and SAH were 47, 22, 11, and 10 (34.1%,
      15.9%, 7.8%, 7.2%), respectively. There was no significant increase in hemorrhage
      with mode of delivery, seizures, hypo/hypercarbia, severe thrombocytopenia, or
      deranged coagulation. All hemorrhages increased with higher HIE stage, regardless
      of the HIE severity in MRI. Adjusting for HIE staging, cooling, and gestation,
      IPH was observed more in infants who received inotropes (odds ratio [OR], 3.32;
      95% confidence interval [CI], 1.20, 9.20). CONCLUSION:  SDH followed by IPH were
      the most common ICH. Thrombocytopenia and deranged coagulation did not increase
      risk of hemorrhages in HIE. Our study was not powered to determine the impact of
      inotrope use on the risk of IPH.

PMID- 29220855
TI  - Use of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation
      Patients with Malignancy: Clinical Practice Experience in a Single Institution
      and Literature Review.
AB  - This observational study aimed to investigate the efficacy and safety of non
      vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF)
      patients with malignancy. A total of 76 patients (mean age: 73.2 +/- 8.9; 28
      females) with AF and malignancy treated with NOAC were included in the analysis.
      The mean CHA2DS2-VASc and HAS-BLED scores were 3.2 +/- 1.2 and 2.2 +/- 0.9,
      respectively. The study population was taking dabigatran 150 mg (25%) twice daily
      (BID), apixaban 5 mg BID (25%), dabigatran 110 mg BID (24%), rivaroxaban 20 mg
      (18%) once a day (OD), rivaroxaban 15 mg OD (5%), or apixaban 2.5 mg OD (3%).
      NOAC therapy began, on average, 248 +/- 238 days before malignancy diagnosis for
      an average duration of 1,000 +/- 289 days. Stroke, transient ischemic attack,
      major and minor bleeding events, other adverse effects, and major cardiovascular
      complications during the follow-up period were collected. In our study
      population, no patients experienced thromboembolic events during therapy with any
      NOAC. We recorded a low global incidence of major bleeding (3.9%) with a mean
      annual incidence of 1.4%. No hemorrhagic stroke or subarachnoid hemorrhage was
      observed. Only nine patients (11.8%) experienced minor bleeding. According to our
      data, anticoagulation therapy with NOACs seems to be an effective and safe
      treatment strategy for nonvalvular AF patients with malignancy.

PMID- 29220857
TI  - Surfactant Administration through Laryngeal Mask Airway: A Randomized Controlled
      Study in Rabbits.
AB  - BACKGROUND:  Minimally invasive techniques for surfactant administration for
      infants with respiratory distress syndrome (RDS) of moderate severity have been
      proposed. The laryngeal mask airway (LMA) helps in securing the airway without
      the need of laryngoscopy, but still requires the use of positive pressure
      ventilation (PPV) to flush surfactant into the lungs. OBJECTIVE:  This article
      compares the effectiveness of two techniques for LMA surfactant administration,
      instillation into the LMA lumen followed by PPV versus direct laryngeal
      instillation through a preinserted feeding tube inside the LMA during spontaneous
      respirations. STUDY DESIGN:  This is a randomized controlled trial (RCT) of 18
      rabbits with acquired respiratory distress after lung lavage. After surfactant
      was given, the rabbits remained on continuous positive airway pressure (CPAP).
      Gas exchange parameters were assessed at baseline and at 30 minutes and lung
      parenchyma pathology features were analyzed. RESULTS:  Time required for
      surfactant administration, oxygenation improvement, and histopathologic findings
      did not differ between groups. The new technique decreased the need of PPV (p <
      0.05). CONCLUSION:  In this animal model, surfactant administration through a
      preinserted feeding tube within the LMA lumen is safe and effective while
      providing the benefits of a minimally invasive approach. This technique reduces
      the need of PPV and may prevent its potential risks.

PMID- 29220858
TI  - Long-term successful closure of a percutaneous intragastric trocar tract with
      crossing full-thickness sutures in a porcine model.
AB  - BACKGROUND AND STUDY AIMS:  A novel intragastric trocar placed using a
      percutaneous endoscopic gastrostomy technique enables the use of laparoscopic
      tools and procedures, including tissue stapling, cutting, suturing, and
      retraction. The aim of this porcine study was to determine long-term success of
      crossing full-thickness sutures in closure of the tract upon trocar withdrawal.
      METHODS:  10 trocars were placed in 5 animals. Each animal underwent a
      standardized tissue resection using a 5-mm stapler under gastroscopic guidance,
      and two full-thickness, absorbable, crossing sutures were used to close the
      trocar tracts. The animals were monitored for 35 days and then euthanized for
      necropsy. RESULTS:  All five animals survived without sign of infection or
      distress. Nine of the 10 trocar sites healed completely without any adverse
      findings. A single site developed a gastrocutaneous fistula. On necropsy, there
      was no evidence of intra-abdominal infection or abscess. CONCLUSIONS:  Full
      thickness crossing sutures appeared to be effective in long-term closure of an
      intragastric trocar tract. Given the ease of placement and success of this simple
      closure method, this device may prove clinically useful to the endoscopist
      performing complex procedures in the endoscopy suite.

PMID- 29220859
TI  - Single- and double-tunnel endoscopic submucosal tunnel dissection for large
      superficial esophageal squamous cell neoplasms.
AB  - BACKGROUND AND STUDY AIM:  Single-tunnel endoscopic submucosal tunnel dissection
      (ESTD) has shown promising preliminary efficacy for large superficial esophageal
      squamous cell neoplasms (SESCNs). This study reports the outcomes of both single-
      and double-tunnel ESTD for large SESCNs, and compares the efficiency of the two
      techniques for treating circumferential SESCNs. PATIENTS AND METHODS:  46
      patients with large SESCNs underwent ESTD at a single hospital between October
      2011 and March 2016. Relevant clinical data were retrospectively collected and
      analyzed. RESULTS:  For all patients, the en bloc and R0 resection rates were
      95.7 % and 82.6 %, respectively. Perforation and cardiac mucosal laceration were
      detected in 2.2 % (1/46) and 6.5 % (3/46) of the procedures, respectively.
      Postoperative stenosis occurred in 12 patients (26.1 %). Of the 18 patients with
      circumferential lesions, those who received a double-tunnel ESTD procedure (n =
      6) underwent dissection faster than those who had a single-tunnel ESTD procedure
      (n = 12) (0.32 vs. 0.12 cm2/min; P = 0.02). CONCLUSION:  ESTD was effective for
      large SESCNs. The double-tunnel ESTD appeared to decrease operative time compared
      with single-tunnel ESTD for circumferential lesions.

PMID- 29220860
TI  - Patients' willingness to defer resection of diminutive polyps: results of a
      multicenter survey.
AB  - BACKGROUND AND STUDY AIMS : Current colonoscopy practice requires removal of
      diminutive polyps. This is associated with costs, but the benefits to colorectal
      cancer (CRC) prevention remain unclear. The study aim was to understand patients'
      willingness to defer resection of diminutive polyps and to examine the factors
      that influence patients' decisions. PATIENTS AND METHODS : Adults presenting for
      a colonoscopy were surveyed at three hospitals in the USA and Canada. Survey
      domains included: patient characteristics, risk perception, knowledge about CRC
      risk, willingness to defer polyp resection, and associated concerns. The primary
      endpoint was the proportion of patients who would be willing to participate in a
      clinical trial that deferred resection of diminutive polyps. Secondary endpoints
      included factors associated with willingness to defer diminutive polyp resection.
      RESULTS : 557 eligible individuals completed the survey (mean age 63; 61 % men),
      with 50 % of respondents being willing to participate in a randomized trial in
      which resection of diminutive polyps would be deferred until the next
      surveillance colonoscopy (95 % confidence interval [CI] 46 % - 55 %). Outside of
      a clinical trial, 57 % of participants would be agreeable to deferring resection
      of diminutive polyps (95 %CI 51 % - 63 %). Willingness to defer diminutive polyp
      resection was associated with higher education (P = 0.001), greater knowledge
      about cancer risk (P = 0.002), and a lower perception of cancer risk (all P <
      0.001). Age, sex, income, a history of polyps, and a first-degree family member
      with CRC were not associated with willingness to defer diminutive polyp
      resection. CONCLUSIONS : More than half of individuals undergoing a routine
      colonoscopy would be agreeable to deferring resection of diminutive polyps and
      participating in a trial to evaluate this approach.

PMID- 29220861
TI  - Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety,
      Efficacy, and Necessity for a New Regulatory Framework.
AB  - Given the expanding market of plant food supplements (PFSs) not undergoing any
      pre-marketing authorization, the overall quality, safety and efficacy of PFSs
      were subjected to a critical examination. Although many high-quality PFSs exist
      on the legal market, quality concerns are in general justified. Besides economic
      adulteration, active ingredients dramatically differing from label claims and
      among products were reported in several studies. In addition, PFSs sold via the
      Internet may be intentionally adulterated with undeclared prescription drugs.
      Compared to PFSs with only one single herb, PFSs containing herbal mixtures were
      more involved in moderate and severe clinical courses. Although prohibited by
      regulation, misleading labels on PFSs are common. Above all, only vague evidence
      for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and
      insufficient safety assessment, PFSs represent a relevant source for consumers to
      get access to herbal preparations in the United States and meanwhile also in
      Europe, as launching of licensed/registered European herbal medicinal products
      (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products,
      PFSs are neither food nor drugs. In terms of protecting public health and
      providing the consumer with high-quality, effective, and safe PFSs, possibilities
      are shown how to deal with the many challenges of PFSs. Last but not least,
      suggestions are made for assigning PFSs a separate regulatory category being less
      regulated compared to HMPs but more strictly regulated compared to food laws
      including implementation of good manufacturing practices and a scientific pre
      marketing review process by an expert commission.

PMID- 29220862
TI  - A descriptive analysis of sleep and wakefulness states during maternal behaviors
      in postpartum rats.
AB  - Mother rats spend most of their time nursing their litter during the early stages
      of the postpartum period, only occasionally leaving the nest. The suckling
      stimulus from the pups elicits the adoption of nursing postures, during which
      milk ejection occurs, an event associated with the occurrence of non-REM (NREM)
      sleep in the rat. Despite this evidence, the characteristics of sleep during
      different nursing postures along the postpartum period remain unknown. The
      present study aims to describe the sleep pattern of mother rats while nursing,
      hovering over their pups and when being away from the pups. For this purpose,
      lactating females were implanted with electrodes for chronic polysomnographic
      recording. Simultaneous recordings of sleep-wakefulness cycle and maternal
      behaviors were performed in both the light and dark phases of the first and
      second postpartum weeks. Results indicate that while mothers were most of the
      time awake when hovering over pups and when staying away from pups, they mainly
      remained in NREM sleep when adopting low kyphosis posture, the most common
      nursing posture. The sleep-wake pattern during most maternal behaviors was quite
      stable between the light and dark phases of the first and second postpartum
      weeks. In addition, the sleep fragmentation was higher during the nursing bouts
      compared to that observed when mother rats slept without the pups, but sleep
      depth did not differ between these behaviors. Our results provide an original
      description of how mother rats synchronize their own sleep-wakefulness cycle with
      the maternal care of the pups during the postpartum period.

PMID- 29220863
TI  - A small dose of apomorphine counteracts the deleterious effects of middle
      cerebral artery occlusion in different models.
AB  - The present manuscript investigates in two animal species by using two different
      experimental models of middle cerebral artery occlusion (permanent and
      transient), the neuroprotective effects of the dopamine receptor agonist
      apomorphine. These effects were evaluated by measuring the infarct volume and by
      counting muscle strength at different time points following the ischemic insult.
      Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the
      occlusion of the middle cerebral artery was able to reduce significantly the
      infarct volume in the cortex of mice and the ischemic volume of the basal ganglia
      perfused by the perforant branches of the middle cerebral artery in the rat. In
      this latter case the behavioral evaluation (i.e. muscle strength) was preserved
      most effectively in the contralateral side at 24 and 72 hours. The present
      findings contribute to foster the concept that DA agonists might be useful in the
      treatment of cerebral ischemia. At the same time the behavioral improvement
      induced by DA administration following basal ganglia ischemia may be interpreted
      as the effects of an authentic disease modifying effect rather than a simple
      symtomatic relief due to a potential loss of DA containing axons in the basal
      ganglia. These data add on previous evidence showing analogous effects induced by
      the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective
      effect induced by increased DA stimulation the present data call for further
      studies aimed at comparing the effects of apomorphine with other DA agonists. In
      fact the quinoline moiety of apomorphine was claimed to protect neurons from a
      variety of insults independently from a DA agonist activity. The induction of
      protein clearing pathways appears to be potentially relevant for these effects.

PMID- 29220864
TI  - The nature of catecholamine-containing neurons in the enteric nervous system in
      relationship with organogenesis, normal human anatomy and neurodegeneration.
AB  - The gastrointestinal tract is provided with extrinsic and intrinsic innervation.
      The extrinsic innervation includes the classic vagal parasympathetic and
      sympathetic components, with afferent sensitive and efferent secretomotor fibers.
      The intrinsic innervations is represented by the enteric nervous system (ENS),
      which is recognized as a complex neural network controlling a variety of cell
      populations, including smooth muscle cells, mucosal secretory cells, endocrine
      cells, microvasculature, immune and inflammatory cells. This is finalized to
      regulate gastrointestinal secretion, absorption and motility. In particular, this
      network is organized in several plexuses each one providing quite autonomous
      control of gastrointestinal functions (hence the definition of "second brain").
      The similarity between ENS and CNS is further substantiated by the presence of
      local sensitive pseudo- unipolar ganglionic neurons with both peripheral and
      central branching which terminate in the enteric wall. A large variety of neurons
      and neurotransmitters takes part in the ENS. However, the nature of these neurons
      and their role in the regulation of gastrointestinal functions is debatable. In
      particular, the available literature reporting the specific nature of
      catecholamine- containing neurons provides conflicting evidence. This is critical
      both for understanding the specific role of each catecholamine in the gut and,
      mostly, to characterize specifically the enteric neuropathology occurring in a
      variety of diseases. An emphasis is posed on neurodegenerative disorders, such as
      Parkinson's disease, which is associated with the loss of catecholamine neurons.
      In this respect, the recognition of the nature of such neurons within the ENS
      would contribute to elucidate the pathological mechanisms which produce both CNS
      and ENS degeneration and to achieve more effective therapeutic approaches.
      Despite a great emphasis is posed on the role of noradrenaline to regulate
      enteric activities only a few reports are available on the anatomy and physiology
      of enteric dopamine neurons. Remarkably, this review limits the presence of
      enteric noradrenaline (and adrenaline) only within extrinsic sympathetic nerve
      terminals. This is based on careful morphological studies showing that the only
      catecholamine-containing neurons within ENS would be dopaminergic. This means
      that enteric pathology of catecholamine neurons should be conceived as axon
      pathology for noradrenaline neurons and whole cell pathology for dopamine neurons
      which would be the sole catecholamine cell within intrinsic circuitries affecting
      gut motility and secretions.The gastrointestinal tract is provided with extrinsic
      and intrinsic innervation. The extrinsic innervation includes the classic vagal
      parasympathetic and sympathetic components, with afferent sensitive and efferent
      secretomotor fibers. The intrinsic innervations is represented by the enteric
      nervous system (ENS), which is recognized as a complex neural network 
      controlling a variety of cell populations, including smooth muscle cells, mucosal
      secretory cells, endocrine cells, microvasculature, immune and inflammatory
      cells. This is finalized to regulate gastrointestinal secretion, absorption and
      motility. In particular, this network is organized in several plexuses each one
      providing quite autonomous control of gastrointestinal functions (hence the
      definition of "second brain"). The similarity between ENS and CNS is further
      substantiated by the presence of local sensitive pseudounipolar ganglionic
      neurons with both peripheral and central branching which terminate in the enteric
      wall. A large variety of neurons and neurotransmitters takes part in the ENS.
      However, the nature of these neurons and their role in the regulation of
      gastrointestinal functions is debatable. In particular, the available literature
      reporting the specific nature of catecholamine-containing neurons provides
      conflicting evidence. This is critical both for understanding the specific role
      of each catecholamine in the gut and, mostly, to characterize specifically the
      enteric neuropathology occurring in a variety of diseases. An emphasis is posed
      on neurodegenerative disorders, such as including Parkinson's disease, which is
      associated with the loss of catecholamine neurons. In this respect, the
      recognition of the nature of such neurons within the ENS would contribute to
      elucidate the pathological mechanisms which produce both CNS and ENS degeneration
      and to achieve more effective therapeutic approaches. Despite a great emphasis is
      posed on the role of noradrenaline to regulate enteric activities only a few
      reports are available on the anatomy and physiology of enteric dopamine neurons.
      Remarkably, this review limits the presence of enteric noradrenaline (and
      adrenaline) only within extrinsic sympathetic nerve terminals. This is based on
      careful morphological studies showing that the only catecholamine-containing
      neurons within ENS would be dopaminergic. This means that enteric pathology of
      catecholamine neurons should be conceived as axon pathology for noradrenaline
      neurons and whole cell pathology for dopamine neurons which would be the sole
      catecholamine cell within intrinsic circuitries affecting gut motility and
      secretions.

PMID- 29220865
TI  - Silver nano particles ameliorate learning and spatial memory of male Wistar rats
      by prevention of amyloid fibril-induced neurotoxicity.
AB  - Alzheimer's disease (AD) is a chronic degenerative disease characterized by the
      presence of amyloid plaques and neurofibrillary tangles (NFTs), which results
      into memory and learning impairments. In the present study, we showed that the
      aggregates formed by a protein that has no link with Alzheimer's disease, namely
      the hen egg white lysozyme (HEWL), were cytotoxic and decreased spatial learning
      and memory in rats. The effect of Ag-nano particles (Ag-NPs) was investigated on
      disruption of amyloid aggregation and preservation of cognitive behavior of rats.
      Twenty-four male Wistar rats were divided into 4 groups including a control
      group, and injected with either scopolamine, lysozyme or aggregates pre-incubated
      with Ag-NPs. Rats' behavior was monitored using Morris water maze (MWM) twenty
      days after injections. HEWL aggregation in the presence and absence of the Ag-NPs
      was assayed by Thioflavin T binding, atomic force microscopy and cell-based
      cytotoxicity assay. Ag-NPs were capable to directly disrupt HEWL oligomerization
      and the resulting aggregates were non-toxic. We also showed that rats of the Ag
      NPs group found MWM test platform in less time and with less distance traveled,
      in comparison with lysozyme group. Ag-NPs also increased the percentage of time
      elapsed and the distance swum in the target quadrant in the rat model of AD, in
      probe test. These observations suggest that Ag-NPs improved spatial learning and
      memory by inhibiting amyloid fibril-induced neurotoxicity. Furthermore, we
      suggest using model proteins as a valid tool to investigate the pathogenesis of
      Alzheimer's disease.

PMID- 29220866
TI  - Neural correlates of fatigue in multiple sclerosis: a combined neurophysiological
      and neuroimaging approach (R1).
AB  - The present study is aimed at further exploring structural and functional
      correlates of fatigue in Relapsing- Remitting Multiple Sclerosis (RRMS) patients
      by using a combined approach by means of transcranial magnetic stimulation (TMS)
      and a Diffusion Tensor Imaging (DTI). The physiopathology of fatigue in MS is
      still poorly understood, although a variety of pathogenic mechanisms has been
      proposed. Our working hypothesis is that diffuse microstructural white matter
      damage may subtend the cortico-subcortical functional disconnection described in
      patients with MS and fatigue. We enrolled 30 RRMS patients (mean age 39+/-13; age
      range 24-63 years) with mild neurological impairment Expanded Disability Status
      Scale <3.5, divided into two groups on the basis of their fatigue severity scale
      (FSS) scoring (cutoff >= 4). All the patients underwent a neurological
      evaluation, a brain MRI acquisition (including DTI study) and a
      neurophysiological assessment by means of TMS in a pre-movement facilitation
      paradigm. Our data showed a significant mean diffusivity (MD) increase (p=0.036)
      in left thalamo-frontal reconstructions in the MS patients with fatigue compared
      to those classified as non-fatigued. Moreover, significant correlations were
      observed between FSS scale and MD as well as planar coefficient (CP) values
      extracted from frontal-thalamic connections bilaterally. Instead, the pre
      movement facilitation showed a significant difference between the groups with
      particular regard to the Reaction Time- MEP50ms amplitude (p=0.03). Our work
      confirms that fatigue is associated with a disruption of brain networks involved
      in motor preparation processes, depending on several frontal-thalamic pathways.
      Such findings can have an important role when dealing with fatigue management in
      MS patients and could be eventually used as prognostic marker of MS course.

PMID- 29220867
TI  - Sarcomeric TPM3alpha in developing chicken.
AB  - Cloning and sequencing of various tropomyosin isoforms expressed in chickens have
      been described since the early 1980s. However, to the best of our knowledge, this
      is the first report on the molecular characterization and the expression of the
      sarcomeric isoform of the TPM3 gene in cardiac and skeletal muscles from
      developing as well as adult chickens. Expression of TPM3alpha was performed by
      conventional RT-PCR as well as qRT-PCR using relative expression (by DeltaCT as
      well as DeltaDeltaCT methods) and by determining absolute copy number. The
      results employing all these methods show that the expression level of TPM3alpha
      is maximum in embryonic (10-day/15-day old) skeletal muscle and can barely be
      detected in both cardiac and skeletal muscles from the adult chicken. Our various
      RT-PCR analyses suggest that the expression of high molecular weight TPM3
      isoforms are regulated at the transcription level from the proximal promoter at
      the 5'-end of the TPM3 gene.

PMID- 29220869
TI  - Non-obese fatty liver disease is associated with lacunar infarct.
AB  - BACKGROUND/AIMS: Lacunar infarct, a small subcortical ischaemic lesion, is a
      known risk factor for future cognitive impairment, dementia and stroke. We
      evaluated the relationship between fatty liver disease (FLD) and lacunar infarct
      in a healthy general population. METHODS: Subjects who underwent brain magnetic
      resonance imaging (MRI) and abdominal ultrasonography (US) during health check
      ups from 2007 to 2009 were included. FLD was diagnosed by US. Subjects with a
      history of cerebrovascular disease, radiological findings consistent with
      cerebrovascular stenosis or cerebral small vessel disease were excluded. RESULTS:
      Of the 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had
      FLD. Subjects with lacunar infarct had a higher prevalence of FLD (59.3% vs
      39.4%, P = .004). There was significant interaction between obesity (BMI < 25
      kg/m2 vs >= 25 kg/m2 ) and FLD for lacunar infarct (P for interaction = .024).
      Subgroup analysis revealed that non-obese FLD was more common in the subjects
      with lacunar infarct than those without (51.7% vs 23.5%, P = .001). However,
      there was no significant difference in the obese FLD prevalence between these 2
      groups. In multivariate models adjusted by age, sex, smoking, alcohol,
      hypertension and diabetes, FLD was significantly associated with lacunar infarct
      (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.08-3.58; P = .027). Non
      obese FLD was associated with lacunar infarct (OR 3.58; 95% CI 1.63-7.89; P =
      .002); however, this association remained insignificant in obese FLD. Instead,
      ageing and hypertension were independent risk factors for lacunar infarct in the
      obese population. CONCLUSIONS: FLD is significantly associated with lacunar
      infarct, independent of traditional risk factors. This association was prominent
      in the non-obese population.

PMID- 29220868
TI  - Incidence and prevalence of hepatitis B in patients with diabetes mellitus in the
      UK: A population-based cohort study using the UK Clinical Practice Research
      Datalink.
AB  - We assessed the incidence and prevalence of hepatitis B (Hep B) in patients with
      or without diabetes mellitus (DM) using the UK Clinical Practice Research
      Datalink (CPRD). This was a retrospective, observational study of diabetic and
      nondiabetic cohorts aged 0-80 years using CPRD (NCT02324218). Incidence rates
      (IR) for each cohort were calculated. Crude and adjusted (Poisson regression) IR
      ratios (IRR) were estimated with 95% confidence intervals (CI) to compare the
      cohorts. Hep B prevalence stratified by age, and hospitalization related to Hep B
      was also calculated. Of 7 712 043 subjects identified, 4 839 770 were included
      (DM: 160 760; non-DM: 4 679 010). Mean ages were 54.4 and 32.0 years, and 57.20%
      and 50.14% were male in the diabetic and nondiabetic cohorts, respectively. Hep B
      was identified in 29 diabetic and 845 nondiabetic subjects; IR was 4.03 per 100
      000 person-years and 2.88 per 100 000 person-years, respectively. The adjusted
      IRR was 1.00 (95% CI: 0.70-1.50) between diabetic and nondiabetic cohorts. Hep B
      prevalence was higher in the diabetic cohort (0.01%-0.26%) than in the
      nondiabetic cohort (0.00%-0.03%) across the different age groups. Hep B
      associated hospitalization IR was higher in the diabetic cohort (4.98-10.91) than
      the nondiabetic cohort (0.26-2.44). The Hep B IR, hospitalization and prevalence
      were higher in males in both cohorts. In conclusion, the risk of incident Hep B
      diagnosis in the diabetic cohort was not different from that in the nondiabetic
      cohort. However, prevalence of Hep B and Hep B-associated hospitalization rate
      was higher in the diabetic than in the nondiabetic cohort.

PMID- 29220870
TI  - Quantitative assessment of informative immunophenotypic markers increases the
      diagnostic value of immunophenotyping in mature CD5-positive B-cell neoplasms.
AB  - BACKGROUND: The data on the clinical utility of the quantitative assessment of
      immunophenotypes in distinguishing mature CD5-positive B-cell neoplasms is
      limited. The study aim was to assess the diagnostic value of the quantitative
      assessment of a panel of 18 markers and to identify the most informative ones.
      METHODS: The immunophenotype of the neoplastic population was determined in
      diagnostic specimens from 188 patients. BD FACSCanto II flow cytometer and
      FACSDiva software were used to analyze the positivity/negativity and mean
      fluorescence intensity (MFI) of the surface expression of 18 markers. Advanced
      data mining methods were used to define the key differential diagnostic features
      of CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), MCL (mantle
      cell lymphoma), and CD5+ MZL (marginal zone lymphoma). RESULTS: The most
      informative markers for the distinction of CLL/SLL, MCL, CD5+ MZL, including
      atypical cases, were the MFI values of CD79b, CD20, CD23, CD43, CD38, CD11c,
      FMC7, CD200, kappa light chain, and their combinations. CD23 and CD200 were the
      most discriminant between CLL/SLL and MCL and CD23 plus CD79b between CLL/SLL and
      CD5+ MZL. The quantitative analysis of the most informative markers failed to
      accurately distinguish MCL and CD5+ MZL. The study highlights the data mining
      methods for the analysis and selection of the most informative immunophenotypic
      markers and for the design of a predictive model (diagnostic classifier),
      minimizing the subjectivity of expert-based assessment. CONCLUSIONS: Our data
      confirmed that the quantification of the expression of informative markers
      increases the diagnostic value of immunophenotyping in mature CD5+ B-cell
      neoplasms. (c) 2017 International Clinical Cytometry Society.

PMID- 29220871
TI  - Role of flow-cytometric immunophenotyping in prediction of BCR/ABL1 gene
      rearrangement in adult B-cell acute lymphoblastic leukemia.
AB  - We performed a retrospective analysis of 88 adult patients with B-ALL diagnosed
      in our center by a flow-cytometric assessment. Immunophenotypic expression of
      leukemic cells was explored by simultaneous evaluation of positivity, percentage
      of expressing cells and median fluorescence intensity (MFI). BCR/ABL1 fusion
      transcripts were assessed by RT-PCR analysis and were identified in 36 patients
      (40.9%). CD10 and CD34 were positive in the totality of BCR/ABL1-positive cases.
      Patients with gene rearrangement had a greater frequency of CD66c, CD13 and CD33
      positivity compared with BCR/ABL1-negative cases. Moreover, BCR/ABL1-positive
      cases exhibited a greater median percentage and MFI values of CD13, CD33, CD66c,
      CD10, CD34 and CD25 expressions, but a lower median percentage and MFI values of
      CD38 and CD22 expressions than patients without gene rearrangement. Multivariate
      logistic regression analysis showed that CD10, CD38 and CD13 expressions were
      independent predictors for the presence of BCR/ABL1 rearrangement. Predictive
      probabilities of molecular occurrence based on these markers are proposed. (c)
      2017 International Clinical Cytometry Society.

PMID- 29220872
TI  - New hydrazide-hydrazones of isonicotinic acid: synthesis, lipophilicity and in
      vitro antimicrobial screening.
AB  - This study describes the synthesis, lipophilicity and in vitro antimicrobial
      assays of 15 new hydrazide-hydrazones of isonicotinic acid. New derivatives were
      obtained on the basis of the condensation reaction of isonicotinic acid hydrazide
      with different aromatic aldehydes. The chemical structure of synthesized
      compounds was confirmed by spectral methods. Experimental lipophilicity of new
      isonicotinic acid derivatives was determined using reversed-phase thin-layer
      chromatography. All synthesized compounds were subjected to in vitro
      antimicrobial assays against reference strains of Gram-positive bacteria, Gram
      negative bacteria and fungi belonging to Candida spp. Some of the synthesized
      hydrazide-hydrazones proved to be significant antibacterial compounds and more
      potent than commonly used chemotherapeutic agents.

PMID- 29220874
TI  - Evolution of larval competitiveness and associated life-history traits in
      response to host shifts in a seed beetle.
AB  - Resource competition is frequently strong among parasites that feed within small
      discrete resource patches, such as seeds or fruits. The properties of a host can
      influence the behavioural, morphological and life-history traits of associated
      parasites, including traits that mediate competition within the host. For seed
      parasites, host size may be an especially important determinant of competitive
      ability. Using the seed beetle, Callosobruchus maculatus, we performed
      replicated, reciprocal host shifts to examine the role of seed size in
      determining larval competitiveness and associated traits. Populations ancestrally
      associated with either a small host (mung bean) or a large one (cowpea) were
      switched to each other's host for 36 generations. Compared to control lines
      (those remaining on the ancestral host), lines switched from the small host to
      the large host evolved greater tolerance of co-occurring larvae within seeds
      (indicated by an increase in the frequency of small seeds yielding two adults),
      smaller egg size and higher fecundity. Each change occurred in the direction
      predicted by the traits of populations already adapted to cowpea. However, we did
      not observe the expected decline in adult mass following the shift to the larger
      host. Moreover, lines switched from the large host (cowpea) to the small host
      (mung bean) did not evolve the predicted increase in larval competitiveness or
      egg size, but did exhibit the predicted increase in body mass. Our results thus
      provide mixed support for the hypothesis that host size determines the evolution
      of competition-related traits of seed beetles. Evolutionary responses to the two
      host shifts were consistent among replicate lines, but the evolution of larval
      competition was asymmetric, with larval competitiveness evolving as predicted in
      one direction of host shift, but not the reverse. Nevertheless, our results
      indicate that switching hosts is sufficient to produce repeatable and rapid
      changes in the competition strategy and fitness-related traits of insect
      populations.

PMID- 29220873
TI  - Effect of sleep on overnight cerebrospinal fluid amyloid beta kinetics.
AB  - Sleep disturbances are associated with future risk of Alzheimer disease.
      Disrupted sleep increases soluble amyloid beta, suggesting a mechanism for sleep
      disturbances to increase Alzheimer disease risk. We tested this response in
      humans using indwelling lumbar catheters to serially sample cerebrospinal fluid
      while participants were sleep-deprived, treated with sodium oxybate, or allowed
      to sleep normally. All participants were infused with 13 C6 -leucine to measure
      amyloid beta kinetics. We found that sleep deprivation increased overnight
      amyloid beta38, amyloid beta40, and amyloid beta42 levels by 25 to 30% via
      increased overnight amyloid beta production relative to sleeping controls. These
      findings suggest that disrupted sleep increases Alzheimer disease risk via
      increased amyloid beta production. Ann Neurol 2018;83:197-204.

PMID- 29220875
TI  - Interleukin-21 receptor signalling is not critically required for imiquimod
      induced psoriasiform dermatitis in mice.
AB  - Psoriasis is largely mediated by interleukin (IL)-23/T helper (Th) 17 axis, and
      IL-21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously
      reported possible pathogenic roles of IL-21 in human psoriasis, we found that IL
      21 receptor (IL-21R) signalling was not crucial for imiquimod-induced psoriatic
      inflammation, using IL-21R-/- mice. The severity of imiquimod-induced psoriatic
      manifestation and pro-inflammatory Th17 cytokine levels, IL-17A-producing
      gammadelta T cells and CD4+ T cells, and in vitro IL-17A production by gammadelta
      T cells after IL-23 stimulation was comparable between wild-type and IL-21R-/-
      mice. Collectively, IL-21R signalling was not critically involved in IMQ-induced
      psoriatic inflammation despite an increased IL-21 expression in the IMQ-treated
      mouse skin. Our data may represent the significant differences between human
      psoriasis and murine psoriasis model, and further studies using other models will
      be required to elucidate the role of IL-21 in psoriasis pathogenesis.

PMID- 29220876
TI  - Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate:
      randomized comparison with active control in congenital fibrinogen deficiency.
AB  - : Essentials Congenital afibrinogenemia causes a potentially life-threatening
      bleeding and clotting tendency. Two human fibrinogen concentrates (HFCs) were
      compared in a randomized pharmacokinetic study. Bioequivalence was not shown for
      AUCnorm , which was significantly larger for the new HFC. Increases in clot
      strength were comparable, and no thromboses or deaths occurred in the study.
      SUMMARY: Background Human fibrinogen concentrate (HFC) corrects fibrinogen
      deficiency in congenital a-/hypofibrinogenemia. Objectives To assess
      pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF),
      and safety of a new double virus-inactivated/eliminated, highly purified HFC vs.
      active control. Patients/Methods In this multinational, randomized, phase II,
      open-label, crossover study in 22 congenital afibrinogenemia patients aged >= 12
      years, 70 mg kg-1 of new HFC (FIBRYGA, Octapharma AG) or control
      (Haemocomplettan(r) P/RiaSTAPTM, CSL Behring GmbH) were administered, followed by
      crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma
      were assessed. Results The concentrates were not bioequivalent for the primary
      endpoint, AUCnorm (mean ratio, 1.196; 90% confidence interval [CI], 1.117,
      1.281). Remaining PK parameters (Cmaxnorm , IVR, t1/2 , MRT) reflected
      bioequivalence between concentrates, except for clearance (mean ratio, 0.836; 90%
      CI, 0.781, 0.895) and Vss (mean ratio, 0.886; 90% CI, 0.791, 0.994). Mean AUCnorm
      was significantly larger for the new HFC (1.62 +/- 0.45 vs. 1.38 +/- 0.47 h kg g
      L-1  mg-1 , P = 0.0001) and mean clearance was significantly slower (0.665 +/-
      0.197 vs. 0.804 +/- 0.255 mL h-1  kg-1 , P = 0.0002). Mean MCF increased from 0
      mm to 9.68 mm (new HFC) and 10.00 mm (control) 1-hour post-infusion (mean
      difference, -0.32 mm; 95% CI, -1.70, 1.07, n.s.). No deaths, thromboses, viral
      seroconversions or serious related adverse events occurred. Conclusions
      Bioequivalence was not demonstrated for AUCnorm , clearance and Vss . Larger
      AUCnorm and slower clearance were observed for the new HFC. Remaining
      pharmacokinetic parameters reflected bioequivalence to control. Safety profiles
      and increases in clot strength were comparable between concentrates.

PMID- 29220877
TI  - Increased circulating plasma cells detected by flow cytometry predicts poor
      prognosis in patients with plasma cell myeloma.
AB  - BACKGROUND: Flow cytometry (FC) is a reliable tool for diagnosing and monitoring
      of plasma cell myeloma (PCM). Recent studies used FC for quantifying plasma cells
      (PCs) in peripheral blood (PB) using various panels, and an adverse prognostic
      effect of circulating PCs (cPCs) has been reported. We investigated the
      prognostic implication of cPCs quantified using a simple panel in patients with
      PCM. METHODS: Bone marrow (BM) and PB of 85 patients with PCM were analyzed by
      five-color FC at time of diagnosis. A serial gating strategy for quantification
      used CD38/CD138 to gate PCs in 100,000-200,000 acquired events, with subsequent
      gating for CD19, CD56, and CD45, to identify aberrant immunophenotypes. RESULTS:
      cPCs were observed in 74.1% patients (63/85, median 0.067% leukocytes). Patients
      were grouped based on a cPC cut-off level of 0.02% derived using the receiver
      operating characteristic curves. Compared with patients with cPCs < 0.02% (n =
      28), those with cPCs >= 0.02% (n = 57) showed lower hemoglobin (P = 0.003) and
      platelets (P = 0.014), but higher calcium, M-protein and BM PCs (P = 0.013,
      0.029, and P < 0.001, respectively). Survival analysis of 74 patients showed that
      cPCs >= 0.02% predicted shorter progression-free and overall survival (P = 0.001
      and 0.013, respectively), and this negative prognostic impact was retained in
      multivariate analysis (P = 0.023). CONCLUSIONS: Flow cytometric quantification of
      cPCs using five surface antigens (CD138, CD38, CD56, CD19, and CD45) is a
      sensitive and simple method that can be used for assessing PCM prognosis; it
      would allow clinical laboratories to readily adopt a risk stratification strategy
      based on cPC levels in PCM patients. (c) 2017 International Clinical Cytometry
      Society.

PMID- 29220878
TI  - A qualitative study of the experience of lower extremity wounds and amputations
      among people with diabetes in Philadelphia.
AB  - The purpose of this study was to explore perceptions among people with type 2
      diabetes about foot ulcers and lower extremity amputations. This was a
      qualitative observational study utilizing open-ended, semistructured interviews
      of 39 people with diabetes who were purposively selected because they had either
      a foot ulcer (n = 19) or a lower extremity amputation (n = 20). Interviews were
      audio-recorded, deidentified, and entered into NVivo 10.0 for coding and
      analysis. Our integrated analytic approach combined inductively and deductively
      derived codes that were applied to all transcripts. Coded data were summarized
      and examined for patterns. Participants' description of the relationship between
      diabetes and their foot ulcer or amputation revealed a limited understanding of
      the disease process. Disruption and loss of independence was expressed whether
      the person had a foot ulcer or an amputation. Treatment recommendations for foot
      ulcers were viewed by most as extremely difficult. Amputation was a feared
      outcome, but some learned to adapt and, at times felt that the amputation
      enhanced their quality of life. Clinicians have assumed that a focus on limb
      salvage is preferred over a major amputation. However, because of the complexity
      of care requiring frequent healthcare provider visits, the frequency of care
      failure, the frequency of recurrence, and mortality associated with having had a
      foot ulcer, it may be more appropriate for clinicians to prioritize quality-of
      life salvage. Foot ulcer treatment failure may be due to a lack of providers'
      understanding of the impact of treatment on a patient's life.

PMID- 29220879
TI  - Detection and a functional characterization of the novel FBN1 intronic mutation
      underlying Marfan syndrome: case presentation.

PMID- 29220880
TI  - Development of a new biochip array for APOE4 classification from plasma samples
      using immunoassay-based methods.
AB  - BACKGROUND: Apolipoprotein E (APOE) is a key player in lipid transport and
      metabolism and exists in three common isoforms: APOE2, APOE3 and APOE4. The
      presence of the E4 allelic variant is recognized as a major genetic risk factor
      for dementia and other chronic (neuro)degenerative diseases. The availability of
      a validated assay for rapid and reliable APOE4 classification is therefore
      advantageous. METHODS: Biochip array technology (BAT) was successfully applied to
      identify directly the APOE4 status from plasma within 3 h, through simultaneous
      immunoassay-based detection of both specific APOE4 and total APOE levels.
      RESULTS: Samples (n=432) were first genotyped by polymerase chain reaction (PCR),
      and thereafter, using BAT, the corresponding plasma was identified as null,
      heterozygous or homozygous for the E4 allele by calculating the ratio of APOE4 to
      total APOE protein. Two centers based in Austria and Ireland correctly classified
      170 and 262 samples, respectively, and achieved 100% sensitivity and specificity.
      CONCLUSIONS: This chemiluminescent biochip-based sandwich immunoarray provides a
      novel platform to detect rapidly and accurately an individual's APOE4 status
      directly from plasma. The E4 genotype of individuals has been shown previously to
      affect presymptomatic risk, prognosis and treatment response for a variety of
      diseases, including Alzheimer's disease. The biochip's potential for being
      incorporated in quantitative protein biomarker arrays capable of analyzing
      disease stages makes it a superior alternative to PCR-based APOE genotyping and
      may deliver additional protein-specific information on a variety of diseases in
      the future.

PMID- 29220881
TI  - The UGT1A1*28 gene variant predicts long-term mortality in patients undergoing
      coronary angiography.
AB  - BACKGROUND: Uridine diphosphate glycosyltransferases 1A1 (UGT1A1) plays an
      essential role in detoxification and excretion of several endogenous and
      exogenous compounds. A functional polymorphism in the promoter of the UGT1A1 gene
      (TA repeat insertion, UGT1A1*28, rs3064744) has been associated with reduced
      UGT1A1 enzyme activity. The purpose of the present study was to investigate the
      role of UGT1A1 genotypes in mortality. METHODS: UGT1A1 genotypes as well as
      baseline plasma bilirubin levels were analyzed in participants of the
      Ludwigshafen Risk and Cardiovascular Health study (n=3316). UGT1A1*28 genotypes
      were determined on an ABI PRISM 3730 genetic analyzer. RESULTS: As expected,
      UGT1A1 genotypes were associated with baseline bilirubin levels (*1/*1 genotype:
      9.1+/-4.6 umol/L; *1/*28 genotype: 10.8+/-5.3; *28/*28: 16.9+/-9.2; p<0.001).
      During a median follow-up of 10.4 years, 995 subjects (30.0%) died. In a
      multivariate regression analysis adjusting for age, sex, smoking, type 2
      diabetes, dyslipidemia, alanine aminotransferase (ALT) levels and bilirubin
      levels, the UGT1A1*28 variant predicted lower overall mortality (hazard ratio
      [HR], 0.86; 95% confidence interval [CI], 0.78-0.95; p=0.003). Contrary to
      expected, higher baseline bilirubin levels predicted increased mortality (HR,
      1.014; 95% CI, 1.002-1.025; p=0.019). CONCLUSIONS: The UGT1A1*28 gene variant is
      associated with lower mortality rates. The protective effect of the UGT1A1*28
      variant likely includes mechanism other than bilirubin metabolism.

PMID- 29220882
TI  - A specific abnormal scattergram of peripheral blood leukocytes that may suggest
      hairy cell leukemia.

PMID- 29220883
TI  - Association of adrenal hormone metabolites and mortality over a 6-year follow-up
      in COPD patients with acute exacerbation.
AB  - BACKGROUND: The release of hormones from the adrenal gland is vital in acute and
      chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving
      recurrent exacerbations. Using a metabolomic approach, we aim to investigate
      associations of different adrenal hormone metabolites with short- and long-term
      mortality in COPD patients. METHODS: We prospectively followed 172 COPD patients
      (median age 75 years, 62% male) from a previous Swiss multicenter trial. At
      baseline, we measured levels of a comprehensive spectrum of adrenal hormone
      metabolites, including glucocorticoid, mineralocorticoid and androgen hormones by
      liquid chromatography coupled with tandem mass spectrometry (MS). We calculated
      Cox regression models adjusted for gender, age, comorbidities and previous
      corticosteroid therapy. RESULTS: Mortality was 6.4% after 30 days and increased
      to 61.6% after 6 years. Higher initial androgen hormones predicted lower long
      term mortality with significant results for dehydroepiandrosterone (DHEA)
      [adjusted hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.98;
      p=0.026] and dehydroepiandrosterone sulfate (DHEA-S) (adjusted HR, 0.68; 95% CI,
      0.50-0.91; p=0.009). An activation of stress hormones (particularly cortisol and
      cortisone) showed a time-dependent effect with higher levels pointing towards
      higher mortality at short term, but lower mortality at long term. Activation of
      the mineralocorticoid axis tended to be associated with increased short-term
      mortality (adjusted HR of aldosterone, 2.76; 95% CI, 0.79-9.65; p=0.111).
      CONCLUSIONS: Independent of age, gender, corticosteroid exposure and exacerbation
      type, adrenal hormones are associated with mortality at short and long term in
      patients with COPD exacerbation with different time-dependent effects of
      glucocorticoids, androgens and mineralocorticoids. A better physiopathological
      understanding of the causality of these effects may have therapeutic
      implications.

PMID- 29220884
TI  - A Black Swan in clinical laboratory practice: the analytical error due to
      interferences in immunoassay methods.
AB  - It is well known that the results of immunoassay methods can be affected by
      specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence
      of interference may greatly compromise the accuracy of immunoassay analyses
      causing an error in the measurement, producing false-positive or false-negative
      results. From a clinical point of view, these analytical errors may have serious
      implications for patient care because they can cause misdiagnosis or
      inappropriate treatment. Unfortunately, it is a very difficult task to identify
      the irregular analytical errors related to immunoassay methods because they are
      not detectable by normal laboratory quality control procedures, are reproducible
      within the test system, may be clinically plausible and are relatively rare. The
      first line of defense against erroneous results is to use in laboratory practice
      only immunoassay systems with the highest level of robustness against
      interference. The second line of defense is always taking into account the
      possibility of interference in immunoassay results. A correct approach should be
      addressed on identification of samples at high risk of interference. The
      attainment of this goal requires a critical review of the test result in relation
      to patient's clinical conditions and literature data, taking into account the
      analytical characteristics of the immunoassay system. The experts in immunoassay
      systems should make every effort to find some specific and reliable quality
      indicators for irregular analytical errors in order to better detect and monitor
      erroneous immunoassay results due to specific or non-specific interferences.

PMID- 29220913
TI  - Editorial.

PMID- 29220885
TI  - Indexes of the erythropoietin level in the blood plasma of chronic heart failure
      patients with anemia.
AB  - BACKGROUND: Anemia aggravates the disease course and the survival rate of chronic
      heart failure (CHF) patients. The purpose of the study was to investigate the
      level of erythropoietin (EPO) in CHF patients with anemic syndrome, with the aim
      to more accurately assess the severity of the disease and its treatment,
      depending on the anemia degree. METHODS: Patients with ischemic CHF of I-IV
      functional class (FC) with and without anemia were examined (total number of
      patients=208, patients with anemia=174). The EPO was determined using the enzyme
      linked immunosorbent assay. Before treatment, the patients underwent the
      following medical therapy: angiotensin-converting enzyme inhibitors, angiotensin
      II receptor blockers, long-acting nitrates, diuretics, digoxin, and beta-blockers
      at individual doses. Depending on the plasma EPO level, the CHF patients with
      anemia were divided into four randomized groups in terms of treatment. RESULTS:
      Normal erythropoietinemia was found in 36.2% of the CHF patients with anemic
      syndrome (I-III FC), hypoerythropoietinemia in 44.8% (III-IV FC), and
      hypererythropoietinemia in 18.96% (III-V FC). The EPO level in the blood plasma
      of the patients with I-II FC CHF with hypoerythropoietinemia, who were treated
      with methoxy polyethylene glycol-epoetin beta (MEB), increased by 2.2 times.
      Combination therapy with disease-modifying drugs and MEB led to a significant
      increase in the plasma EPO level in the CHF patients with hypoerythropoietinemia.
      CONCLUSIONS: It was shown that the EPO level in patients with CHF and anemia did
      not always drop. Hypererythropoietinemia in patients with CHF and anemia leads to
      an unfavorable treatment prediction. This necessitates the investigation of the
      EPO level in all patients with CHF before and after treatment, with the aim of
      correcting the anemic syndrome. The research showed that the combined therapy of
      patients with CHF and anemia using MEB medication and iron with regard to the EPO
      level in the blood plasma improved their overall physical condition, reduced
      heart failure symptoms and hospitalization frequency, and demonstrated a clear
      tendency to reduce the general mortality rate.

PMID- 29220955
TI  - Online High-throughput Mutagenesis Designer Using Scoring Matrix of Sequence
      specific Endonucleases.
AB  - CRISPR Cas9 and other sequence-specific endonucleases are fundamental genome
      editors supporting gene knockout and gene therapy. A speedy and accurate
      computational allele designer is required for a high through-put gene mutagenesis
      pipeline using these new techniques. An automatic system, Cas9 online designer
      (COD), was created to screen Cas9 targets and off-targets, as well as to provide
      gene knockout and genotyping strategies. A gene knockout rat model was
      successfully created and genotyped under the direction of this online system
      confirming its ability to predict real targets and off-targets. Gene knockout
      strategies to mutate 72 rat cytochrome P450 genes were designed instantly by the
      system to demonstrate its high-throughput efficiency. Also, the system used an
      off-target scoring matrix which can be applied to any sequence-specific genome
      editing tools besides Cas9. The COD system (http://cas9.wicp.net) has established
      a speedy, accurate, flexible and high through-put computational gene knockout
      pipeline supporting the sequence-specific endonuclease induced mutagenesis.

PMID- 29220979
TI  - Selecting the optimal synthesis parameters of InP/CdxZn1-xSe quantum dots for a
      hybrid remote phosphor white LED for general lighting applications.
AB  - Quantum dots can be used in white LEDs for lighting applications to fill the
      spectral gaps in the combined emission spectrum of the blue pumping LED and a
      broad band phosphor, in order to improve the source color rendering properties.
      Because quantum dots are low scattering materials, their use can also reduce the
      amount of backscattered light which can increase the overall efficiency of the
      white LED. The absorption spectrum and narrow emission spectrum of quantum dots
      can be easily tuned by altering their synthesis parameters. Due to the re
      absorption events between the different luminescent materials and the light
      interaction with the LED package, determining the optimal quantum dot properties
      is a highly non-trivial task. In this paper we propose a methodology to select
      the optimal quantum dot to be combined with a broad band phosphor in order to
      realize a white LED with optimal luminous efficacy and CRI. The methodology is
      based on accurate and efficient simulations using the extended adding-doubling
      approach that take into account all the optical interactions. The method is
      elaborated for the specific case of a hybrid, remote phosphor white LED with
      YAG:Ce phosphor in combination with InP/CdxZn1-xSe type quantum dots. The
      absorption and emission spectrum of the quantum dots are generated in function of
      three synthesis parameters (core size, shell size and cadmium fraction) by a semi
      empirical 'quantum dot model' to include the continuous tunability of these
      spectra. The sufficiently fast simulations allow to scan the full parameter space
      consisting of these synthesis parameters and luminescent material concentrations
      in terms of CRI and efficacy. A conclusive visualization of the final performance
      allows to make a well-considered trade-off between these performance parameters.
      For the hybrid white remote phosphor LED with YAG:Ce and InP/CdxZn1-xSe quantum
      dots a CRI Ra = 90 (with R9>50) and an overall efficacy of 110 lm/W is found.

PMID- 29220980
TI  - Modeling the single and multiple scattering properties of soot-laden mineral dust
      aerosols.
AB  - Fractal particle morphologies are employed to study the light scattering
      properties of soot-laden mineral dust aerosols. The applicability of these models
      is assessed in comparison with measurements and other numerical studies. To
      quantify the dust-soot mixing effects on the single and multiple scattering
      properties, a parameterization of the effective bulk properties is developed.
      Based on the parameterized bulk properties, polarized one-dimensional radiative
      transfer simulations are performed. The results indicate that small uncertainties
      in conjunction with soot contamination parameters may lead to large uncertainties
      in both forward and inverse modeling involving mineral dust contaminated with
      soot.

PMID- 29220981
TI  - Influence of luminescent material properties on stimulated emission luminescent
      solar concentrators (SELSCs) using a 4-level system.
AB  - The effect of various design and material parameters on the efficiency of
      stimulated emission-based luminescent solar concentrators (SELSCs) is studied
      numerically using a 4-level luminescent material containing concentrator. It is
      shown that the most efficient SELSCs have emission wavelengths of 1.5-1.8 um,
      with a strong dependence on the Stokes shift. Depending on the parameters of the
      system, spontaneous emission is shown to nevertheless account for a significant
      fraction of potential energy generation. Assuming a propagation loss constant of 
      0.1m-1, and a refractive index of 1.5, the optimal length of an SELSC is found to
      be ~1.5m. Given these losses and an efficiency target of 10% greater than
      traditional LSCs, the required material emission linewidth varies from 10 to
      100nm, with maximum thicknesses of 3-30 um. Further, when reflection and
      propagation losses are considered, a single laser pass is preferred over multiple
      passes. It is also shown that SELSCs are significantly less sensitive to
      luminescent quantum efficiency when compared to conventional LSCs due to the
      increased radiative emission rate.

PMID- 29220982
TI  - Photonic thermal diode enabled by surface polariton coupling in nanostructures.
AB  - A novel photonic thermal diode concept operating in the near field and
      capitalizing on the temperature-dependence of coupled surface polariton modes in
      nanostructures is proposed. The diode concept utilizes terminals made of the same
      material supporting surface polariton modes in the infrared, but with dissimilar
      structures. The specific diode design analyzed in this work involves a thin film
      and a bulk, both made of 3C silicon carbide, separated by a subwavelength vacuum
      gap. High rectification efficiency is obtained by tuning the antisymmetric
      resonant modes of the thin film, resulting from surface phonon-polariton
      coupling, on- and off-resonance with the resonant mode of the bulk as a function
      of the temperature bias direction. Rectification efficiency is investigated by
      varying structural parameters, namely the vacuum gap size, the dielectric
      function of the substrate onto which the film is coated, and the film thickness
      to gap size ratio. Calculations based on fluctuational electrodynamics reveal
      that high rectification efficiencies in the 80% to 87% range can be maintained in
      a wide temperature band (~700 K to 1000 K). The rectification efficiency of the
      proposed diode concept can potentially be further enhanced by investigating more
      complex nanostructures such as gratings and multilayered media.

PMID- 29220983
TI  - Biomimetic spiral grating for stable and highly efficient absorption in
      crystalline silicon thin-film solar cells: erratum.
AB  - In the original manuscript, the maximum short-circuit current in Fig. 2 and the
      description of angular stability for polarization in Fig. 6 are found incorrect
      owing to negligence. The incorrect maximum integrated absorption also led to
      errors appeared in Fig. 3 and Fig. 4(d), in which the mistake value was used to
      plot. In this erratum, all of those mistakes have been corrected. Moreover, both
      higher Fourier expansion order and the resolution of frequency are adopted in the
      recalculation to make sure the updated results to be reliable. The updated data
      presented still support the main conclusions drawn in the previous manuscript.

PMID- 29220984
TI  - Plasma nanotexturing of silicon surfaces for photovoltaics applications:
      influence of initial surface finish on the evolution of topographical and optical
      properties.
AB  - Using a plasma to generate a surface texture with feature sizes on the order of
      tens to hundreds of nanometers ("nanotexturing") is a promising technique being
      considered to improve efficiency in thin, high-efficiency crystalline silicon
      solar cells. This study investigates the evolution of the optical properties of
      silicon samples with various initial surface finishes (from mirror polish to
      various states of micron-scale roughness) during a plasma nanotexturing process.
      It is shown that during said process, the appearance and growth of nanocone-like
      structures are essentially independent of the initial surface finish, as
      quantified by the auto-correlation function of the surface morphology. During the
      first stage of the process (2 min to 15 min etching), the reflectance and light
      trapping abilities of the nanotextured surfaces are strongly influenced by the
      initial surface roughness; however, the differences tend to diminish as the
      nanostructures become larger. For the longest etching times (15 min or more), the
      effective reflectance is less than 5% and a strong anisotropic scattering
      behavior is also observed for all samples, leading to very elevated levels of
      light-trapping.

PMID- 29220985
TI  - Tungsten-based highly selective solar absorber using simple nanodisk array.
AB  - In this paper, we report the design, fabrication, and characterization of a
      tungsten-based metamaterial selective solar absorber (SSA) combining a metal
      insulator-metal (MIM) structure and simple nanodisk array. The as-fabricated
      absorber absorbs strongly and selectively in the wavelength range of 0.5-1.75 MUm
      with a characterized absorptance of more than 90%, which drops abruptly to less
      than 12.6% beyond 2.5 MUm. In addition, this broadband and highly selective
      absorber is polarization-insensitive under incidence of normal plane waves.
      Moreover, the solar selectivity remains invariable up to 40 degrees , which is
      beneficial for solar thermal applications. These properties are verified
      theoretically and experimentally in the present work. Further analysis on energy
      dissipation reveals the underlying physics and optical performances.

PMID- 29220986
TI  - Determination of the absorption coefficient of chromophoric dissolved organic
      matter from underway spectrophotometry.
AB  - Measurements of the absorption coefficient of chromophoric dissolved organic
      matter (ay) are needed to validate existing ocean-color algorithms. In the
      surface open ocean, these measurements are challenging because of low ay values.
      Yet, existing global datasets demonstrate that ay could contribute between 30% to
      50% of the total absorption budget in the 400-450 nm spectral range, thus making
      accurate measurement of ay essential to constrain these uncertainties. In this
      study, we present a simple way of determining ay using a commercially-available
      in-situ spectrophotometer operated in underway mode. The obtained ay values were
      validated using independent collocated measurements. The method is simple to
      implement, can provide measurements with very high spatio-temporal resolution,
      and has an accuracy of about 0.0004 m-1 and a precision of about 0.0025 m-1 when
      compared to independent data (at 440 nm). The only limitation for using this
      method at sea is that it relies on the availability of relatively large volumes
      of ultrapure water. Despite this limitation, the method can deliver the ay data
      needed for validating and assessing uncertainties in ocean-colour algorithms.

PMID- 29220987
TI  - Demonstration of a diode-laser-based high spectral resolution lidar (HSRL) for
      quantitative profiling of clouds and aerosols.
AB  - We present a demonstration of a diode-laser-based high spectral resolution lidar.
      It is capable of performing calibrated retrievals of aerosol and cloud optical
      properties at a 150 m range resolution with less than 1 minute integration time
      over an approximate range of 12 km during day and night. This instrument operates
      at 780 nm, a wavelength that is well established for reliable semiconductor
      lasers and detectors, and was chosen because it corresponds to the D2 rubidium
      absorption line. A heated vapor reference cell of isotopic rubidium 87 is used as
      an effective and reliable aerosol signal blocking filter in the instrument. In
      principle, the diode-laser-based high spectral resolution lidar can be made cost
      competitive with elastic backscatter lidar systems, yet delivers a significant
      improvement in data quality through direct retrieval of quantitative optical
      properties of clouds and aerosols.

PMID- 29220988
TI  - Toward high performance nanoscale optoelectronic devices: super solar energy
      harvesting in single standing core-shell nanowire.
AB  - Single nanowire solar cells show great promise for next-generation photovoltaics
      and for powering nanoscale devices. Here, we present a detailed study of light
      absorption in a single standing semiconductor-dielectric core-shell nanowire
      (CSNW). We find that the CSNW structure can not only concentrate the incident
      light into the structure, but also confine most of the concentrated light to the
      semiconductor core region, which boosts remarkably the light absorption cross
      section of the semiconductor core. The CSNW can support multiple higher-order HE
      modes, as well as Fabry-Perot (F-P) resonance, compared to the bare nanowire
      (BNW). Overlapping of the adjacent higher-order HE modes results in broadband
      light absorption enhancement in the solar radiation spectrum. Results based on
      detailed balance analysis demonstrate that the super light concentration of the
      single CSNW gives rise to higher short-circuit current and open-circuit voltage,
      and thus higher apparent power conversion efficiency (3644.2%), which goes far
      beyond that of the BNW and the Shockley-Queisser limit that restricts the
      performance of a planar counterparts. Our study shows that the single CSNW can be
      a promising platform for construction of high performance nanoscale
      photodetectors, nanoelectronic power sources, super miniature cells, and diverse
      integrated nanosystems.

PMID- 29220989
TI  - Biases in ocean color over a Secchi disk.
AB  - The oldest record of ocean color measurements consists of visual comparisons to a
      standardized color scale, the Forel-Ule scale (FU). Analysis of FU archived data
      allows the construction of a century-long time series. In situ protocols of FU
      measurements require the perceived color to be estimated over the water column
      above a Secchi disk (SD) at half of the depth where it goes out of sight, whereas
      satellites retrieve FU over the water column alone. I show in this article that
      these two methodologies lead to different FU readings and thus, merging both
      kinds of data will create artificial trends. In case 1 waters, radiative transfer
      simulations show that measuring over a SD shifts FU between 0 and + 2 in respect
      to no SD, and there exists no possibility to relate the two in a univocal
      fashion. A univocal relationship is found if color is expressed in terms of the
      hue angle, which can be calculated from light spectra or RGB images.

PMID- 29220990
TI  - Laser induced photocatalytic activity enhancement of TiO2 thin films.
AB  - In this paper, the photocatalytic activity enhancement of TiO2 thin films was
      realized by laser irradiation. The H2 yield of the as-irradiated film is 79
      MUmol/(h*m2), which is 33% more than that of the as-deposited TiO2 film.
      Spectrophotometer, X-ray diffraction and Raman system were employed to
      characterize the samples. The results showed that both the scanning rate and line
      spacing of the laser modification have effects on photocatalytic activity. It
      suggests that a phase junction is formed between the amorphous and rutile phases.
      The increment of H2 generation could be attributed to the alignment of Fermi
      levels in the phase junction.

PMID- 29220991
TI  - Assessing uncertainties in scattering correction algorithms for reflective tube
      absorption measurements made with a WET Labs ac-9.
AB  - In situ absorption measurements collected with a WET Labs ac-9 employing a
      reflective tube approach were scatter corrected using several possible methods
      and compared to reference measurements made by a PSICAM to assess performance.
      Overall, two correction methods performed best for the stations sampled: one
      using an empirical relationship between the ac-9 and PSICAM to derive the
      scattering error (epsilon) in the near-infrared (NIR), and one where epsilon was
      independently derived from concurrent measurements of the volume scattering
      function (VSF). Application of the VSF-based method may be more universally
      applicable, although difficult to routinely apply because of the lack of
      commercially available VSF instrumentation. The performance of the empirical
      approach is encouraging as it relies only on the ac meter measurement and may be
      readily applied to historical data, although there are inevitably some inherent
      assumptions about particle composition that hinder universal applicability. For
      even the best performing methods, residual errors of 20% or more were commonly
      observed for many water types. For clear ocean waters, a conventional baseline
      subtraction with the assumption of negligible near-IR absorption performed as
      well or better than the above methods because propagated uncertainties were lower
      than observed with the proportional method.

PMID- 29220992
TI  - All-inorganic perovskite-based distributed feedback resonator.
AB  - Halide perovskite materials have rapidly emerged as outstanding optoelectronic
      materials for solar cells, light-emitting diodes (LEDs), and lasers. Compared to
      hybrid organic-inorganic perovskites, all-inorganic perovskites have shown unique
      merits that may contribute to the ultimate goal of developing electrically-pumped
      lasers. In this paper, we demonstrate a distributed feedback (DFB) resonator
      using an all-inorganic perovskite thin film as the gain medium. The film has a
      gain coefficient of 161.1 cm-1 and a loss coefficient of 30.9 cm-1. Excited by
      picosecond pulses, the microstructured all-inorganic perovskite film exhibits a
      single-mode emission at 654 nm with a threshold of 33 MUJ/cm2. The facile
      fabrication process provides a promising route towards low-cost single-mode
      visible lasers for many practical applications.

PMID- 29220993
TI  - Spectral signature of nonlinear effects in semiconductor optical amplifiers.
AB  - Optical spectra of signals at the output of semiconductor optical amplifiers
      (SOA) provide useful insight into amplifier nonlinearities. In this work, we
      determine the parameters of an analytical SOA model with a pump-probe experiment
      by evaluating the measured spectra of the pump and probe pulses at the SOA
      output. The analytical lumped SOA model considers carrier depletion, carrier
      recovery, spectral hole burning, two-photon absorption, and we include an
      additional effect termed 'two-photon induced free-carrier absorption', that is
      responsible for creating an identifiable blue-shifted component in the spectra.
      We are able to relate the underlying physical nonlinear effects to the spectral
      peculiarities of the output pump and probe spectra, and give guidelines for the
      exploitation of these nonlinear effects for optical signal processing. In
      addition, with a much-simplified SOA model and by replacing the pump pulse with
      modulated data we show that the output spectrum is altered in a manner consistent
      with phase patterning effects.

PMID- 29220994
TI  - Numerical investigation of a scalable setup for efficient terahertz generation
      using a segmented tilted-pulse-front excitation.
AB  - A hybrid-type terahertz pulse source is proposed for high energy terahertz pulse
      generation. It is the combination of the conventional tilted-pulse-front setup
      and a transmission stair-step echelon-faced nonlinear crystal with a period
      falling in the hundred-micrometer range. The most important advantage of the
      setup is the possibility of using plane parallel nonlinear optical crystal for
      producing good-quality, symmetric terahertz beam. Another advantage of the
      proposed setup is the significant reduction of imaging errors, which is important
      in the case of wide pump beams that are used in high energy experiments. A one
      dimensional model was developed for determining the terahertz generation
      efficiency, and it was used for quantitative comparison between the proposed new
      hybrid setup and previously introduced terahertz sources. With lithium niobate
      nonlinear material, calculations predict an approximately ten-fold increase in
      the efficiency of the presently described hybrid terahertz pulse source with
      respect to that of the earlier proposed setup, which utilizes a reflective stair
      step echelon and a prism shaped nonlinear optical crystal. By using pump pulses
      of 50 mJ pulse energy, 500 fs pulse length and 8 mm beam spot radius,
      approximately 1% conversion efficiency and 0.5 mJ terahertz pulse energy can be
      reached with the newly proposed setup.

PMID- 29220995
TI  - Phase retrieval of the full vectorial field applied to coherent Fourier
      scatterometry.
AB  - Coherent Fourier scatterometry is an optical metrology technique that utilizes
      the measured intensity of the scattered optical field to reconstruct certain
      parameters of test structures written on a wafer with nano-scale accuracy. The
      intensity of the scattered field is recorded with a camera and this information
      is used to retrieve the grating parameters. To improve sensitivity in the
      parameter reconstruction, the phase of the scattered field can also be acquired.
      Interferometry can be used for this purpose, but with the cost of cumbersomeness.
      In this paper, we show that iterative phase retrieval methods can be applied to
      retrieve the scattered complex fields from only intensity measurement data. We
      show that the accuracy of the retrieved complex fields using phase retrieval is
      comparable to that measured directly using interferometry.

PMID- 29220996
TI  - 8-beam local oscillator array at 4.7 THz generated by a phase grating and a
      quantum cascade laser.
AB  - We present an 8-beam local oscillator (LO) for the astronomically significant
      [OI] line at 4.7 THz. The beams are generated using a quantum cascade laser (QCL)
      in combination with a Fourier phase grating. The grating is fully characterized
      using a third order distributed feedback (DFB) QCL with a single mode emission at
      4.7 THz as the input. The measured diffraction efficiency of 74.3% is in an
      excellent agreement with the calculated result of 75.4% using a 3D simulation. We
      show that the power distribution among the diffracted beams is uniform enough for
      pumping an array receiver. To validate the grating bandwidth, we apply a far
      infrared (FIR) gas laser emission at 5.3 THz as the input and find a very similar
      performance in terms of efficiency, power distribution, and spatial configuration
      of the diffracted beams. Both results represent the highest operating frequencies
      of THz phase gratings reported in the literature. By injecting one of the eight
      diffracted 4.7 THz beams into a superconducting hot electron bolometer (HEB)
      mixer, we find that the coupled power, taking the optical loss into account, is
      in consistency with the QCL power value.

PMID- 29220997
TI  - Compact fiber biocompatible temperature sensor based on a hermetically-sealed
      liquid-filling structure.
AB  - A compact and robust fiber temperature sensor based on a hermetically-sealed
      liquid-filling Fabry-Perot (FP) cavity was fabricated by low-cost but efficient
      processes, including fusion splicing, liquid injection, and fused tapering. Owing
      to the high thermal optical coefficient (TOC) of the ethanol, the optical path
      difference (OPD) in the FP cavity varied strongly with temperature, which
      consequently induced a drastic wavelength shift of the reflection spectrum.
      Meanwhile, the low freezing point of the ethanol caused the fiber sensor to have
      the ability of detecting the sub-zero temperatures. As a result, a linear
      sensitivity as high as 429 pm/ degrees C was achieved in the range between -5 
      degrees C and 30  degrees C. In addition, our fiber temperature sensor also
      exhibited rapid response time, good repeatability, and stability. The
      biocompatible structure, low fabrication cost, and high performance of such a
      temperature sensor can provide it potential for biological applications.

PMID- 29220998
TI  - Characterization and control of a multi-primary LED light lab.
AB  - A new light lab facility has been commissioned at Rochester Institute of
      Technology with the research goal of studying human visual adaptation under
      temporally dynamic lighting. The lab uses five-channel LED luminaires with 16
      bits of addressable depth per channel, addressed via DMX. Based on spectral
      measurements, a very accurate multi-primary additive color model has been built
      that can be used to provide "colorimetric plus" multi-primary channel intensity
      solutions optimized for spectral accuracy, color fidelity, color gamut, or other
      attributes. Several spectral tuning and multi-primary solutions are compared, for
      which accuracy results and IES TM-30-15 color rendition measures are shown.

PMID- 29220999
TI  - Resonant cavity enhanced waveguide transmission for broadband and high efficiency
      quarter-wave plate.
AB  - Existing transmission type optical quarter-wave plates based on metallic sub
      wavelength structures can hardly realize transmission efficiency above 60%. And
      their working bandwidths are still very narrow. In this paper, we demonstrate a
      transmission type quarter-wave plate design with efficiency above 92% over a
      broad wavelength range (from 1260 nm to 1560 nm). The device proposed is based on
      a one-dimensional metal-insulator-metal waveguide array buried in silica. Phase
      difference between transmitted TE and TM components can be tuned continuously. At
      the same time, transmission efficiency can be kept above 90% in the same spectral
      range for both the TE and TM incidences. The broad bandwidth and remarkable
      efficiency are explained with the combination of low dispersion of waveguide
      modes and the resonant cavity enhanced transmission effect. To give a better
      understanding of the structure, we also propose a modified effective medium
      model. The optical response of the structure can be well reproduced with the semi
      analytic effective medium model.

PMID- 29221001
TI  - Two-dimensional grating guided-mode resonance tunable filter.
AB  - A two-dimensional (2D) grating guided-mode resonance (GMR) tunable filter is
      experimentally demonstrated using a low-cost two-step nanoimprinting technology
      with a one-dimensional (1D) grating polydimethylsiloxane mold. For the first
      nanoimprinting, we precisely control the UV LED irradiation dosage and demold the
      device when the UV glue is partially cured and the 1D grating mold is then
      rotated by three different angles, 30 degrees , 60 degrees , and 90 degrees , for
      the second nanoimprinting to obtain 2D grating structures with different crossing
      angles. A high-refractive-index film ZnO is then coated on the surface of the
      grating structure to form the GMR filter devices. The simulation and experimental
      results demonstrate that the passband central wavelength of the filter can be
      tuned by rotating the device to change azimuth angle of the incident light. We
      compare these three 2D GMR filters with differential crossing angles and find
      that the filter device with a crossing angle of 60 degrees  exhibits the best
      performance. The tunable range of its central wavelength is 668-742 nm when the
      azimuth angle varies from 30 degrees  to 90 degrees .

PMID- 29221000
TI  - Compact illumination optic with three freeform surfaces for improved beam
      control.
AB  - Multi-chip and large size LEDs dominate the lighting market in developed
      countries these days. Nevertheless, a general optical design method to create
      prescribed intensity patterns for this type of extended sources does not exist.
      We present a design strategy in which the source and the target pattern are
      described by means of "edge wavefronts" of the system. The goal is then finding
      an optic coupling these wavefronts, which in the current work is a monolithic
      part comprising up to three freeform surfaces calculated with the simultaneous
      multiple surface (SMS) method. The resulting optic fully controls, for the first
      time, three freeform wavefronts, one more than previous SMS designs. Simulations
      with extended LEDs demonstrate improved intensity tailoring capabilities,
      confirming the effectiveness of our method and suggesting that enhanced
      performance features can be achieved by controlling additional wavefronts.

PMID- 29221002
TI  - Distributed spatial mode dispersion measurement along strongly coupled multicore
      fibers based on the correlation analysis of Rayleigh backscattering amplitudes.
AB  - We describe a method for measuring spatial mode dispersion (SMD) distribution
      along a strongly coupled multicore fiber (SC-MCF). The SMD has been defined for
      characterizing an SC-MCF, and it changes with respect to local fiber bending and
      twisting. However, conventional measurement methods characterize only the overall
      SMD, and cannot identify fiber portions where the environmental conditions affect
      the SMD. This paper demonstrates distributed SMD measurement along an SC-MCF by
      auto-correlating Rayleigh backscattering amplitudes obtained with coherent
      optical reflectometry. We confirm our method experimentally, and distinguish the
      difference between the SMD growth along twisted and non-twisted fiber sections in
      concatenated SC-MCFs.

PMID- 29221003
TI  - Controllable multiple plasmonic bending beams via polarization of incident waves.
AB  - Plasmonic bending beams, which preserve their spatial shapes while propagating
      along curved trajectories in metal-dielectric interface, offer important
      applications in the fields of fiber sensor, optical trapping, and micro-nano
      manipulation. In this work, circular hole array, as a local point-like sources of
      surface plasmon polaritons, is designed on the metal film to generate multiple
      plasmonic bending beams. The electric field intensity of multiple plasmonic
      bending beams is controlled by polarization angle of input light. In addition,
      the electric filed intensity of multiple plasmonic bending beams relies on circle
      hole radius. These findings provide guidance in the design and optimization of
      plasmonic bending beam generators.

PMID- 29221004
TI  - Ultrafast dynamics of multi-exciton state coupled to coherent vibration in zinc
      chlorin aggregates for artificial photosynthesis.
AB  - Ultrafast vibronic dynamics induced by the interaction of the Frenkel exciton
      with the coherent molecular vibrations in a layer-structured zinc chlorin
      aggregates prepared for artificial photosynthesis have been studied by 7.1 fs
      real-time vibrational spectroscopy with multi-spectrum detection. The fast decay
      of 100 +/- 5fs is ascribed to the relaxation from the higher multi-exciton state
      (MES) to the one-exciton state, and the slow one of 863 +/- 70fs is assigned to
      the relaxation from Q-exciton state to the dark nonfluorescent charge-transfer
      (CT) state, respectively. In addition, the wavelength dependences of the exciton
      vibration coupling strength are found to follow the zeroth derivative of the
      transient absorption spectra of the exciton. It could be explained in term of the
      transition dipole moment modulated by dynamic intensity borrowing between the B
      transition and the Q transition through the vibronic interactions.

PMID- 29221005
TI  - Manipulating excited state hyperfine level populations in an atomic laser through
      electronic spin polarization: controlling upper laser level degeneracy and small
      Signal Gain.
AB  - Anisotropic coherent radiation has been generated from an isotropic medium, in
      the absence of an external magnetic field, by the spin polarization of an atomic
      excited state. Lasing on specific hyperfine lines of the 6p2P32->6s2S12 (D2)
      transition of Cs at 852.1 nm has been realized by photoexciting Cs-rare gas
      thermal collision pairs with a circularly-polarized (sigma+) optical field.
      Subsequent dissociation of the transient Cs-rare gas B2Sigma12+ diatomic molecule
      selectively populates the F = 4, 5 hyperfine levels of the Cs 6p2P32 state. Not
      only does electronic spin polarization of the upper laser level yield circularly
      polarized coherent emission, but the effective degeneracy (g2) of the 6p2P32
      state is altered by the non-statistical hyperfine state population distribution,
      thereby permitting control of the laser small signal gain with an elliptically
      polarized pump optical field. The D2 laser efficiency and output power correlate
      directly with the molecular orbital structure of the Cs-rare gas B2Sigma+ state
      in the region of internuclear separation at which the diatomic complex is born.

PMID- 29221006
TI  - Optical Peregrine rogue waves of self-induced transparency in a resonant erbium
      doped fiber.
AB  - The resonant interaction of an optical field with two-level doping ions in a
      cryogenic optical fiber is investigated within the framework of nonlinear
      Schrodinger and Maxwell-Bloch equations. We present explicit fundamental rational
      rogue wave solutions in the context of self-induced transparency for the coupled
      optical and matter waves. It is exhibited that the optical wave component always
      features a typical Peregrine-like structure, while the matter waves involve more
      complicated yet spatiotemporally balanced amplitude distribution. The existence
      and stability of these rogue waves is then confirmed by numerical simulations,
      and they are shown to be excited amid the onset of modulation instability. These
      solutions can also be extended, using the same analytical framework, to include
      higher-order dispersive and nonlinear effects, highlighting their universality.

PMID- 29221007
TI  - Energy-aware virtual network embedding in flexi-grid networks.
AB  - Network virtualization technology has been proposed to allow multiple
      heterogeneous virtual networks (VNs) to coexist on a shared substrate network,
      which increases the utilization of the substrate network. Efficiently mapping VNs
      on the substrate network is a major challenge on account of the VN embedding
      (VNE) problem. Meanwhile, energy efficiency has been widely considered in the
      network design in terms of operation expenses and the ecological awareness. In
      this paper, we aim to solve the energy-aware VNE problem in flexi-grid optical
      networks. We provide an integer linear programming (ILP) formulation to minimize
      the electricity cost of each arriving VN request. We also propose a polynomial
      time heuristic algorithm where virtual links are embedded sequentially to keep a
      reasonable acceptance ratio and maintain a low electricity cost. Numerical
      results show that the heuristic algorithm performs closely to the ILP for a small
      size network, and we also demonstrate its applicability to larger networks.

PMID- 29221008
TI  - Efficient strategy to increase higher order inter-modal stability of a step index
      multimode fiber.
AB  - We demonstrate a novel approach to enhance the mode stability through increased
      effective index difference (Deltaneff) between the higher-order modes (LP18, LP09
      and LP19) of a multimode fiber. Fibers with large diameters have bigger effective
      mode areas (Aeff) and can be useful for high power lasers and amplifiers.
      However, a large mode area (LMA) results in an increased number of modes that can
      be more susceptible to mode coupling. The modal effective index difference
      (Deltaneff) strongly correlates with mode stability and this increases as the
      modal order (m) increases. We report here that the mode spacing between the
      higher order modes can be further enhanced by introducing doped concentric rings
      in the core. In our work, we have shown a more than 35% increase in the mode
      spacing between the higher order modes by optimizing the doping profile of a LMA
      fiber. The proposed design technique is also scalable and can be applied to
      improve the mode spacing between different higher order modes and their
      neighboring antisymmetric modes, as necessary.

PMID- 29221009
TI  - Dependence of the amplification performance of unsaturated degenerate phase
      sensitive amplification on wavelength allocation.
AB  - This paper theoretically investigates the dependence of the performance of dual
      pump degenerate phase-sensitive amplification (PSA) on wavelength allocation. A
      fiber-based PSA under unsaturated-gain conditions is considered. Phase mismatch
      is formalized in terms of incident light frequencies, taking the nonlinear phase
      shift into account, based on which PSA performances, such as signal gain, noise
      figure, and phase-clamping effect, are evaluated as a function of the signal
      wavelength. The results quantitatively indicate that these PSA properties are
      degraded as the signal wavelength is detuned from the phase-matched condition.

PMID- 29221010
TI  - Multipoint fiber-optic laser-ultrasonic actuator based on fiber core-opened
      tapers.
AB  - In this study, a novel fiber-optic, multipoint, laser-ultrasonic actuator based
      on fiber core-opened tapers (COTs) is proposed and demonstrated. The COTs were
      fabricated by splicing single-mode fibers using a standard fiber splicer. A COT
      can effectively couple part of a core mode into cladding modes, and the coupling
      ratio can be controlled by adjusting the taper length. Such characteristics are
      used to obtain a multipoint, laser-ultrasonic actuator with balanced signal
      strength by reasonably controlling the taper lengths of the COTs. As a prototype,
      we constructed an actuator that generated ultrasound at four points with a
      balanced ultrasonic strength by connecting four COTs with coupling ratios of
      24.5%, 33.01%, 49.51%, and 87.8% in a fiber link. This simple-to-fabricate,
      multipoint, laser-ultrasonic actuator with balanced ultrasound signal strength
      has potential applications in fiber-optic ultrasound testing technology.

PMID- 29221011
TI  - Profile reconstruction method adopting parameterized re-projection errors of
      laser lines generated from bi-cuboid references.
AB  - A flexible reconstruction method, which is based on the line re-projection errors
      of the laser plane, is presented for the profile recovery. The bi-cuboid
      references are designed to cover the large view-field of the camera. The local
      intrinsic and extrinsic parameter matrices of the camera are initially
      contributed by the RQ decomposition. Then the balance model is demonstrated to
      obtain the global parameter matrices in view of the refined projection in the
      camera coordinate system. The flexible laser plane is solved by the Plucker
      matrices of the projection laser lines that are generated from the homographies
      of the cubical references and the global parameter matrices. Furthermore, the
      laser plane and global parameter matrices are improved by the cost function that
      is constructed by the re-projection errors of the parameterized laser lines on
      the references. The reconstruction experiments are performed to verify the
      validity and the accuracy of the optimization method and the initial method. The
      impact factors of the measurement distance, the reference distance and the test
      distance are investigated in the experiments. The average reconstruction errors
      are 1.14 mm, 1.13 mm, 1.15 mm and 1.17 mm in the four groups of experiments,
      which shows the good application prospect of the profile reconstructions.

PMID- 29221012
TI  - Optical trapping of nanoparticles with tunable inter-distance using a multimode
      slot cavity.
AB  - Optical trapping of nano-objects (i.e., the nano-tweezers) has been investigated
      intensively. Most of those nano-tweezers, however, were focused on the trapping
      of a single nanoparticle, while the interactions between them were seldom
      considered. In this work, we propose a nano-tweezers in a slot photonic crystal
      cavity supporting multiple modes, where the relative positions of two trapped
      nanoparticles can be tuned by selective excitation of different resonant mode.
      Results show that both the nanoparticles are trapped at the center of the cavity
      when the first order mode is excited. When the incident source is tuned to the
      second order mode, however, these two nanoparticles push each other and are
      trapped stably at two separated positions. Also, the inter-distance between them
      can be tuned precisely by changing the relative power of the two modes. This
      provides a potential method to control the interactions between two nano-objects
      via optically tuning the separation between them, and may have applications in
      various related disciplinary.

PMID- 29221013
TI  - Nonlinear beat noise in optical parametric chirped-pulse amplification.
AB  - The pulse contrast of state-of-the-art petawatt lasers is limited by coherent
      noise. This paper reports on a new family of noise, termed nonlinear beat noise,
      which is generated by the nonlinear mixing of two kinds of coherent noise in
      optical parametric chirped-pulse amplification (OPCPA). We theoretically study
      the various nonlinear beat noises and reveal their intensity evolutions in an
      OPCPA amplifier. The results suggest that nonlinear beat noise will be
      destructive to the future hundred-petawatt lasers.

PMID- 29221014
TI  - Digitally controlled multiplexed silicon photonics phase shifter using heaters
      with integrated diodes.
AB  - We present a silicon side heater with integrated diode to provide multiplexed
      control of different elements in a photonic circuit based on the polarity of the
      driving signal. The diode introduces an asymmetric electrical response where the
      heater is only active under forward bias. This can be used to address multiple
      heaters through the same electrical electrical contacts. We demonstrate push-pull
      operation on a Mach-Zehnder interferometer with heaters in both arms, as well as
      time-multiplexed operation of multiple heaters by modulating the driving signal.
      We extend this work by demonstrating how pulse width modulation (PWM) and
      duobinary-PWM can be used to improve the linearity of the response of the phase
      shifters.

PMID- 29221015
TI  - Speckle reduction using angular spectrum interleaving for triangular mesh based
      computer generated hologram.
AB  - We propose a method that eliminates speckle artifact in the reconstruction of
      triangular mesh based computer generated holograms. The proposed method generates
      a number of holograms with different sets of interleaved plane carrier waves. The
      generated holograms are displayed sequentially with time-multiplexing, achieving
      speckle-free reconstruction without sacrificing the viewing angle or depth of
      focus. The proposed method is verified experimentally using viewing-window type
      holographic display setup. The experimental results indicate that the proposed
      method can achieve speckle-free reconstruction with smaller number of the time
      multiplexing than conventional temporal speckle averaging techniques.

PMID- 29221016
TI  - 49.6 Gb/s direct detection DMT transmission over 40 km single mode fibre using an
      electrically packaged silicon photonic modulator.
AB  - We present the characterization of a silicon Mach-Zehnder modulator with
      electrical packaging and show that it exhibits a large third-order
      intermodulation spurious-free dynamic range (> 100 dB Hz2/3). This characteristic
      renders the modulator particularly suitable for the generation of high spectral
      efficiency discrete multi-tone signals and we experimentally demonstrate a single
      channel, direct detection transmission system operating at 49.6 Gb/s, exhibiting
      a baseband spectral efficiency of 5 b/s/Hz. Successful transmission is
      demonstrated over various lengths of single mode fibre up to 40 km, without the
      need of any amplification or dispersion compensation.

PMID- 29221017
TI  - Polarization-switchable and wavelength-controllable multi-functional metasurface
      for focusing and surface-plasmon-polariton wave excitation.
AB  - Realizing versatile functionalities in a single photonic device is crucial for
      photonic integration. We here propose a polarization-switchable and wavelength
      controllable multi-functional metasurface. By changing the polarization state of
      incident light, its functionality can be switched between the flat focusing lens
      and exciting surface-plasmon-polariton (SPP) wave. Interestingly, by tuning the
      wavelength of incident light, the generated SPP waves can also be controlled at
      desired interfaces, traveling along the upper or lower interface of the
      metasurface, or along both of them, depending on whether the incident light
      satisfies the first or second Kerker condition. This polarization-switchable and
      wavelength-controllable multifunctional metasurface may provide flexibility in
      designing tunable or multifunctional metasurfaces and may find potential
      applications in highly integrated photonic systems.

PMID- 29221018
TI  - Classification of symmetry properties of waveguide modes in presence of
      gain/losses, anisotropy/bianisotropy, or continuous/discrete rotational symmetry.
AB  - We study the symmetric properties of waveguide modes in presence of gain/losses,
      anisotropy/bianisotropy, or continuous/discrete rotational symmetry. We provide a
      comprehensive approach to identity the modal symmetry by constructing a 4 * 4
      waveguide Hamiltonian and searching the symmetric operation in association with
      the corresponding waveguides. We classify the chiral/time reversal/parity/parity
      time/rotational symmetry for different waveguides, and provide the criterion for
      the aforementioned symmetry operations. Lastly, we provide examples to illustrate
      how the symmetry operations can be used to classify the modal properties from the
      symmetric relation between modal profiles of several different waveguides.

PMID- 29221019
TI  - Data analysis-based autonomic bandwidth adjustment in software defined multi
      vendor optical transport networks.
AB  - Network operators generally provide dedicated lightpaths for customers to meet
      the demand for high-quality transmission. Considering the variation of traffic
      load, customers usually rent peak bandwidth that exceeds the practical average
      traffic requirement. In this case, bandwidth provisioning is unmetered and
      customers have to pay according to peak bandwidth. Supposing that network
      operators could keep track of traffic load and allocate bandwidth dynamically,
      bandwidth can be provided as a metered service and customers would pay for the
      bandwidth that they actually use. To achieve cost-effective bandwidth
      provisioning, this paper proposes an autonomic bandwidth adjustment scheme based
      on data analysis of traffic load. The scheme is implemented in a software defined
      networking (SDN) controller and is demonstrated in the field trial of multi
      vendor optical transport networks. The field trial shows that the proposed scheme
      can track traffic load and realize autonomic bandwidth adjustment. In addition, a
      simulation experiment is conducted to evaluate the performance of the proposed
      scheme. We also investigate the impact of different parameters on autonomic
      bandwidth adjustment. Simulation results show that the step size and adjustment
      period have significant influences on bandwidth savings and packet loss. A small
      value of step size and adjustment period can bring more benefits by tracking
      traffic variation with high accuracy. For network operators, the scheme can serve
      as technical support of realizing bandwidth as metered service in the future.

PMID- 29221020
TI  - Modified Alvarez lens for high-speed focusing.
AB  - We present a modified configuration of a tunable Alvarez lens with a refocusing
      frequency of 1 kHz or more. In contrast to the classic Alvarez lens, the approach
      does not utilize a translational motion of two sub-lenses with respect to each
      other, but uses a 4f-setup to image two diffractive sub-lenses onto each other.
      Hereby focus tuning is achieved by rotating a galvo-mirror which affects the
      overlap of the two sub-lenses which together form an effective lens of refractive
      power which depends on the rotation angle of the galvo-mirror. We have
      demonstrated tuning of the optical power in a system where the diffractive
      Alvarez lens is realized by an LCOS-SLM. We consider our Alvarez setup especially
      suitable for applications where high refocusing rates are important, as for
      example in 3D life cell monitoring or tracking.

PMID- 29221021
TI  - Solution for error propagation in a NOMA-based VLC network: symmetric
      superposition coding.
AB  - Non-orthogonal multiple access (NOMA) has recently attracted significant
      attention as a promising multiple access scheme for the 5th generation (5G)
      wireless communication due to its superior spectral efficiency, which has also
      been studied and shown to achieve a superior performance in visible light
      communication (VLC) networks. However, the error propagation (EP) problem due to
      successive interference cancellation (SIC) decoding has not yet been resolved,
      which degrades the system BER performance and causes user unfairness. In this
      work, symmetric superposition coding (SSC) and symmetric SIC (SSIC) decoding are
      proposed for a downlink NOMA-based VLC network, in which the distribution of the
      demodulation regions of the user allocated with more power will be symmetrical in
      terms of the decision threshold of the user allocated with less power.
      Furthermore, the proposed method is experimentally tested and the results show
      that more than 90% demodulation errors caused by EP are eliminated compared with
      traditional NOMA VLC.

PMID- 29221022
TI  - Spatiotemporal evolutions of ultrashort vortex pulses generated by spiral multi
      pinhole plate.
AB  - We use the spiral multi-pinhole plate to generate ultrashort vortex pulses and
      study their spatiotemporal evolutions involving intensity, phase, orbital angular
      momentum, and energy current. In the experiment, a Mach-Zehnder-type
      interferometer is employed to perform the investigation of ultrashort vortices.
      Combining the experimental results and the theoretical analyses, we discuss the
      spatiotemporal evolutions of ultrashort vortex pulses in femtosecond regime. The
      results show that the distribution of orbital angular momentum in the cross
      section of the vortex pulse is maintained almost invariable in the pulse
      duration, while both the intensity and the energy current obey a Gaussian-like
      distribution. With time evolution, the phase contour lines of such vortex pulses
      rotate around the propagation axis.

PMID- 29221023
TI  - Comparison of nematic liquid-crystal and DMD based spatial light modulation in
      complex photonics.
AB  - Digital micro-mirror devices (DMDs) have recently emerged as practical spatial
      light modulators (SLMs) for applications in photonics, primarily due to their
      modulation rates, which exceed by several orders of magnitude those of the
      already well-established nematic liquid crystal (LC)-based SLMs. This, however,
      comes at the expense of limited modulation depth and diffraction efficiency. Here
      we compare the beam-shaping fidelity of both technologies when applied to light
      control in complex environments, including an aberrated optical system, a highly
      scattering layer and a multimode optical fibre. We show that, despite their
      binary amplitude-only modulation, DMDs are capable of higher beam-shaping
      fidelity compared to LC-SLMs in all considered regimes.

PMID- 29221024
TI  - RF photonic downconversion of vector modulated signals based on a millimeter-wave
      coupled electrooptic nonlinear polymer phase-modulator.
AB  - We report the RF photonic reception and downconversion of vector modulated RF
      signals using a millimeter-wave coupled electrooptic phase modulator with in
      plane slotted patch antennas based on SEO125 nonlinear polymer. We demonstrate
      experimental results with QPSK, 8-PSK, 16-QAM, 32-QAM, and 64-QAM millimeter-wave
      signals centered at 36 GHz. After downconversion to intermediate frequencies
      between 0.5 GHz and 2 GHz, the vector encoded signals are demodulated using an
      electrical signal analyzer and found to have measured error vector magnitudes
      below 8%. Design, simulation, fabrication, and experimental results are presented
      and discussed.

PMID- 29221025
TI  - Sensitive refractive index sensor based on an assembly-free fiber multi-mode
      interferometer fabricated by femtosecond laser.
AB  - We propose and demonstrate a highly sensitive refractive index (RI) sensor based
      on a novel fiber-optic multi-mode interferometer (MMI), which is formed with a
      femtosecond-laser-induced in-core negative refractive index modified line in a
      standard single mode fiber. The proposed MMI structure is directly written with
      femtosecond laser in one step, which removes the splicing process needed in
      conventional MMI fabrication and also significantly improves the robustness. This
      device exhibits a high sensitivity to surrounding refractive index, with a
      maximum sensitivity up to 10675.9 nm/RIU at the RI range of 1.4484-1.4513. The
      distinct advantages of high sensitivity, compact, robust and assembly-free all
      fiber structure make it attractive for real physical, chemical and biological
      sensing.

PMID- 29221026
TI  - Efficient micro-cavity top emission OLED with optimized Mg:Ag ratio cathode.
AB  - Micro-cavity top-emitting organic light emitting diodes (TEOLEDs) are now
      receiving prominence as a technology for the active matrix display applications.
      The semi-transparent metal cathode plays the crucial role in realizing TEOLEDs
      structure. Here, we report the optimization results on Mg:Ag ratio as the
      semitransparent cathode deposited by vacuum thermal evaporation. The optimized
      Mg:Ag cathode with 1:10 ratio (wt %) shows a sheet resistance value as low as 5.2
      Omega/?, an average transmittance of 49.7%, reflectance of 41.4%, and absorbance
      of 8.9% over the visible spectral region (400~700 nm). The fabricated red TEOLEDs
      device implemented using LiF (1nm)/Mg:Ag (1:10) cathode shows the voltage value
      of 4.17 V at a current density of 10.00 mA/cm2, and current efficiencies
      variation from 55.3 to 50.1 cd/A over the brightness range 2,000 - 12,000 cd/m2.
      The electroluminescence (EL) spectrum displays the light emission at 608 nm
      wavelength with a half width of 29.5 nm. The narrow half-width of red light
      emission is attributed to the micro-cavity effects due to the semitransparent
      cathode.

PMID- 29221027
TI  - Development of a unimorph deformable mirror with water cooling.
AB  - Deformable mirror (DM) used for intracavity compensation in high-power lasers
      should be able to withstand very high laser intensity. This paper proposes a
      water-cooled unimorph DM which can withstand the laser power up to 10 kW in
      thermal simulation. The proposed DM consists of an annular PZT layer and a
      circular Si layer which are glued together with edge clamped. All the 32
      piezoelectric actuators are distributed around the correction area and on the
      front side of the DM. The cooling water flows through the back side of the DM and
      cools the mirror directly. This design realizes the physical separation of the
      actuators and the coolant. The experimental results of a fabricated DM prototype
      show that the DM can reproduce typical low-order aberrations accurately with
      relatively large amplitude. The wavefront PV amplitudes of the reproduced
      tip/tilt, astigmatism, defocus, trefoil and coma shapes for 15 mm aperture are
      about 40 MUm, 24 MUm, 18.7 MUm, 10 MUm and 6 MUm, respectively.

PMID- 29221028
TI  - Cascaded second-order optical nonlinearities in on-chip micro rings.
AB  - We demonstrate cascaded Stimulated Raman Scattering (SRS), Second-Harmonic
      Generation (SHG), and Sum-Frequency Generation (SFG) in integrated on-chip
      whispering-gallery resonators (WGRs). These lithium niobate-based WGRs are
      fabricated using highly-parallel semiconductor manufacturing techniques coupled
      with specialized polishing as a post-processing step and thus represent a novel
      means for batch fabrication of this family of non-linear devices. We achieved
      record high Q-factors for on-chip lithium niobate WGRs reaching up to 3 * 106.
      Furthermore, we present a flexible but stable coupling scheme, which gives us the
      opportunity to optimize the coupling regarding the non-linear optical processes
      we observe.

PMID- 29221029
TI  - Effect of crystalline family and orientation on stimulated Brillouin scattering
      in whispering-gallery mode resonators.
AB  - Ultra-high Q whispering-gallery mode resonators pumped by a continuous-wave laser
      are known to enhance stimulated Brillouin scattering when optimal resonance and
      phase-matching conditions are met. In crystalline resonators, this process
      depends critically on the crystal orientation and family, which impose the
      elastic constants defining the velocity of the acoustic waves. In this article,
      we investigate the effect of crystalline orientation and family on this velocity
      which is proportional to the Brillouin frequency down-shift. In particular, the
      study is based on the development of a model and numerical simulations of
      acoustic wave velocities that propagate along the periphery of four fluoride
      crystals, namely calcium, magnesium, lithium and barium fluoride. We find that
      depending on the crystal and its orientation, the frequency excursion around the
      Brillouin offset can vary from few tens of kHz to more than a GHz.

PMID- 29221030
TI  - Optical camera with liquid crystal autofocus lens.
AB  - A mobile phone camera with an innovative electrically tunable liquid crystal lens
      (TLCL) concept is demonstrated. We first report the comparative theoretical and
      experimental analyses of the performance of a traditional "modal control" TLCL
      versus a TLCL using a floating (unpowered) transparent electrode (FTE). It is
      shown that the appropriate choice of voltage and frequency values of the driving
      electric signal may improve significantly (almost twice) the optical quality of
      the lens using the FTE. Exceptionally low spherical aberrations of the lens (<
      lambda/10 for up to 10 diopters of optical power) and high modulation transfer
      functions of a mobile phone camera (using those lenses for autofocus function)
      are demonstrated in a very simple operation mode (frequency tuning of the lens'
      optical power at a fixed driving voltage). The capacity of the camera to perform
      high quality long distance photography and near distance bar code recognition
      within a short autofocus convergence time are demonstrated.

PMID- 29221031
TI  - Robust interferometer with external phase-shift control.
AB  - We describe a robust interferometer with external phase-shift control that does
      not require moving parts. The optical architecture resembles a common-path device
      in which the interfering waves propagate together in one collimated beam passing
      through the test sample. The collimated beam is incident on a calcite plate,
      which produces a polarization selective lateral translation and superposition of
      the reference and test waves. The characteristic features of the proposed
      interferometer, i.e. one-beam single-element scheme combined with external phase
      shift control without moving parts, make a highly vibration insensitive device.
      Validation experiments are presented.

PMID- 29221032
TI  - Self-calibration phase-shifting algorithm with interferograms containing very few
      fringes based on Fourier domain estimation.
AB  - Based on Fourier domain estimation, a novel self-calibration phase-shifting
      algorithm, named Mid-Band Spatial Spectrum Matching (MSSM), is proposed to
      achieve phase retrieval from a small amount of phase-shifting interferograms
      containing very few fringes (defined as ultra-sparse fringe pattern(USFP)), which
      is still a difficult problem for optical interferometry. Both simulation and
      experimental results demonstrate that the proposed MSSM algorithm can accurately
      and rapidly achieve the phase distribution encoded in USFP while other current
      self-calibration algorithms fail, and this will supply a powerful tool to extend
      the application of phase-shifting interferometry.

PMID- 29221033
TI  - Flexible manipulation of terahertz wave reflection using polarization insensitive
      coding metasurfaces.
AB  - In order to extend to 3-bit encoding, we propose notched-wheel structures as
      polarization insensitive coding metasurfaces to control terahertz wave reflection
      and suppress backward scattering. By using a coding sequence of "00110011..."
      along x-axis direction and 16 * 16 random coding sequence, we investigate the
      polarization insensitive properties of the coding metasurfaces. By designing the
      coding sequences of the basic coding elements, the terahertz wave reflection can
      be flexibly manipulated. Additionally, radar cross section (RCS) reduction in the
      backward direction is less than -10dB in a wide band. The present approach can
      offer application for novel terahertz manipulation devices.

PMID- 29221034
TI  - InP-based photonic integrated circuit platform on SiC wafer.
AB  - We have numerically investigated the properties of an InP-on-SiC wafer as a
      photonic integrated circuit (PIC) platform. By bonding a thin InP-based
      semiconductor on a SiC wafer, SiC can be used as waveguide cladding, a heat sink,
      and a support substrate simultaneously. Since the refractive index of SiC is
      sufficiently low, PICs can be fabricated using InP-based strip and rib waveguides
      with a minimum bend radius of approximately 7 MUm. High-thermal-conductivity SiC
      underneath an InP-based waveguide core markedly improves heat dissipation,
      resulting in superior thermal properties of active devices such as laser diodes.
      The InP-on-SiC wafer has significantly smaller thermal stress than InP-on-SiO2/Si
      wafer, which prevents the thermal degradation of InP-based devices during high
      temperature processes. Thus, InP on SiC provides an ideal platform for high
      performance PICs.

PMID- 29221035
TI  - Integrated radiation and scattering performance of a multifunctional artificial
      electromagnetic surface.
AB  - In this paper, a multifunctional artificial electromagnetic surface (AEMS) with
      integrated radiation and scattering performance is proposed and realized.
      Different from previous AEMS designs that mainly focus on scattering performance,
      this AEMS design takes both radiation and scattering properties into
      consideration in the designing process. Inspired by the design concept of
      antenna, a feeding structure is added to each AEMS element to achieve radiation
      performance. Meanwhile, the concerned characteristics of AEMS elements are almost
      maintained. For achieving wideband low-scattering performance, two different
      kinds of AEMS elements are designed and arranged in a chessboard configuration.
      Simulated and measured results prove that our method offers an effective strategy
      to design multifunctional AEMS that achieve radiation and scattering performance
      simultaneously.

PMID- 29221036
TI  - Direct inscription of Bragg gratings into coated fluoride fibers for widely
      tunable and robust mid-infrared lasers.
AB  - We report the development of a widely tunable all-fiber mid-infrared laser system
      based on a mechanically robust fiber Bragg grating (FBG) which was inscribed
      through the polymer coating of a Ho3+-Pr3+ co-doped double clad ZBLAN fluoride
      fiber by focusing femtosecond laser pulses into the core of the fiber without the
      use of a phase mask. By applying mechanical tension and compression to the FBG
      while pumping the fiber with an 1150 nm laser diode, a continuous wave (CW) all
      fiber laser with a tuning range of 37 nm, centered at 2870 nm, was demonstrated
      with up to 0.29 W output power. These results pave the way for the realization of
      compact and robust mid-infrared fiber laser systems for real-world applications
      in spectroscopy and medicine.

PMID- 29221037
TI  - Large-area highly crystalline WSe2 atomic layers for ultrafast pulsed lasers.
AB  - Large-area and highly crystalline transition metal dichalcogenides (TMDs) films
      possess superior saturable absorption compared to the TMDs nanosheet
      counterparts, which make them more suitable as excellent saturable absorbers (SA)
      for ultrafast laser technology. Thus far, the nonlinear optical properties of
      large-scale WSe2 and its applications in ultrafast photonics have not yet been
      fully investigated. In this work, the saturable absorption of chemical vapor
      deposition (CVD) grown WSe2 films with large-scale and high quality are studied
      and the use of WSe2 films as a broadband SA for passively mode-locked fiber
      lasers at both 1.5 and 2 MUm ranges is demonstrated. To enhance the light
      material interaction, large-area WSe2 film is tightly transferred onto the side
      wall of a microfiber to form a hybrid structure, which realizes strong evanescent
      wave interaction between light and WSe2 film. The integrated microfiber-WSe2
      device shows a large modulation depth of 54.5%. Using the large-area WSe2 as a
      mode-locker, stable soliton mode-locked pulse generation is achieved and the
      pulse durations of 477 fs (at 1.5 MUm) and 1.18 ps (at 2.0 MUm) are demonstrated,
      which suggests that the large-area and highly crystalline WSe2 films afford an
      excellent broadband SA for ultrafast photonic applications.

PMID- 29221038
TI  - Theoretical analysis of electro-refractive index variation in asymmetric Ge/SiGe
      coupled quantum wells.
AB  - We propose and analyze theoretically an asymmetric Ge/SiGe coupled quantum well
      (CQW) for silicon based optical phase modulator. An 8-band k?p model is used to
      calculate the eigenstates and absorption spectra of the CQWs. The simulation
      results exhibit unique physical characteristics owing to the coupling between the
      two wave functions through the thin barriers. We can achieve an electro
      refractive index variation as high as 9 * 10-3 at the wavelength of about 1461 nm
      under the electric field of 30 kV/cm. The product VpiLpi of half-wave voltage and
      length of phase shift region is estimated to be 0.01 V cm. The proposed
      asymmetric Ge/SiGe CQW scheme provides a promising candidate for high speed, low
      voltage, low power consumption and compact optical phase modulators in silicon
      based integrated optoelectronic devices.

PMID- 29221039
TI  - Controlling the interaction between plasmon-induced transparency and guided mode
      resonance.
AB  - A hybrid metamaterial-waveguide (HMW) system, consisting of a plasmon-induced
      transparency (PIT) metamaterial layer deposited on top of a slab waveguide, is
      investigated at mid-infrared wavelengths. The proposed hybrid system supports
      three quasi-guided modes. Two of them are excited through the conventional
      pathway, i.e. directly excited from the free-space waves via the diffractive
      coupling, while the theoretical analysis and numerical simulation both
      demonstrate that the third one undergoes a completely different excitation
      pathway, i.e. induced by the dark plasmon mode via near field coupling. The
      interactions between the three quasi-guided modes and the PIT effect further lead
      to the interesting multi-spectral transmission characteristics that cannot be
      realized in traditional HMW systems. This is the first report, to our best
      knowledge, describing this unconventional excitation mechanism of the quasi
      guided mode as well as the interaction between the quasi-guided waveguide mode
      and PIT effect.

PMID- 29221040
TI  - Polymethyl methacrylate (PMMA) recycling for the production of optical fiber
      sensor systems.
AB  - This paper proposes the recycling of poly (methyl methacrylate) plates, formerly
      used in LCD monitors to produce polymer optical fibers without cladding for
      sensor systems and a discussion about the fabrication process of the fiber
      cladding is briefly presented. After disassembling LCD monitors the acrylic plate
      is cleaned and submitted to an extrusion process. Extrusion temperatures of 220
      degrees C, 230 degrees C and 240 degrees C were applied, and the produced polymer
      fibers were characterized by infrared and visible spectrometry, as well as
      evaluated for thermal analysis through differential scanning calorimetry (DSC)
      and thermal gravimetric analysis (TGA). Furthermore, a refractive index sensor
      was developed with the recycled fibers. Results show that the recycled fiber
      refractive index sensor is linear (R2 = 0.99) and presents a sensitivity of more
      than 4 times higher when compared to a sensor using a commercial POF.

PMID- 29221041
TI  - Design and fabrication of DOEs on multi- freeform surfaces via complex amplitude
      modulation.
AB  - A non-iterative design and precise fabrication method of diffractive optical
      elements (DOEs) on multiple freeform surfaces is proposed and investigated in
      this paper. Complex amplitude modulation (CAM) technology is applied to design
      complicated DOEs. The wave-front for desired DOEs fabrication is interfered with
      a plane wave and then be encoded to a pure phase hologram. Simulations for
      different DOEs (binary and gray scales) on freeform surfaces are performed and
      the relative errors are 0.56% and 0.78%, respectively. Since the reconstructed
      optical fields generated by spatial light modulator (SLM) can be recorded into
      light-sensitive materials (photopolymer), the DOEs fabrication is realized by
      optical exposure. The results show that the proposed method can design and
      fabricate DOEs on multi-freeform surfaces at one time with high quality. Since
      the CAM method ensures precise reconstruction without iterations, the fabrication
      is accurate as well as the design is fast. It is expected that the proposed
      method could be applied in the precise 3D optical fabrication and processing in
      the future.

PMID- 29221042
TI  - Image processing pipeline for segmentation and material classification based on
      multispectral high dynamic range polarimetric images.
AB  - We propose a method for the capture of high dynamic range (HDR), multispectral
      (MS), polarimetric (Pol) images of indoor scenes using a liquid crystal tunable
      filter (LCTF). We have included the adaptive exposure estimation (AEE) method to
      fully automatize the capturing process. We also propose a pre-processing method
      which can be applied for the registration of HDR images after they are already
      built as the result of combining different low dynamic range (LDR) images. This
      method is applied to ensure a correct alignment of the different polarization HDR
      images for each spectral band. We have focused our efforts in two main
      applications: object segmentation and classification into metal and dielectric
      classes. We have simplified the segmentation using mean shift combined with
      cluster averaging and region merging techniques. We compare the performance of
      our segmentation with that of Ncut and Watershed methods. For the classification
      task, we propose to use information not only in the highlight regions but also in
      their surrounding area, extracted from the degree of linear polarization (DoLP)
      maps. We present experimental results which proof that the proposed image
      processing pipeline outperforms previous techniques developed specifically for
      MSHDRPol image cubes.

PMID- 29221043
TI  - Silicon photonic integrated circuit for fast and precise dual-comb distance
      metrology.
AB  - We demonstrate an optical distance sensor integrated on a silicon photonic chip
      with a footprint of well below 1 mm2. The integrated system comprises a
      heterodyne receiver structure with tunable power splitting ratio and on-chip
      photodetectors. The functionality of the device is demonstrated in a synthetic
      wavelength interferometry experiment using frequency combs as optical sources. We
      obtain accurate and fast distance measurements with an unambiguity range of 3.75
      mm, a root-mean-square error of 3.4 um and acquisition times of 14 us.

PMID- 29221044
TI  - Side-lobe level reduction in bio-inspired optical phased-array antennas.
AB  - Phased arrays are expected to play a critical role in visible and infrared
      wireless systems. Their improved performance compared to single element antennas
      finds uses in communications, imaging, and sensing. However, fabrication of
      photonic antennas and their feeding network require long element separation,
      leading to the appearance of secondary radiation lobes and, consequently,
      crosstalk and interference. In this work, we experimentally show that by
      arranging the elements according to the Fermat's spiral, the side lobe level
      (SLL) can be reduced. This reduction is proved in a CMOS-compatible 8-element
      array, revealing a SLL decrement of 0.9 dB. Arrays with larger numbers of
      elements and inter-element spacing are demonstrated through an spatial light
      modulator (SLM) and an SLL drop of 6.9 dB is measured for a 64-element array. The
      reduced SLL, consequently, makes the proposed approach a promising candidate for
      applications in which antenna gain, power loss, or information security are key
      requirements.

PMID- 29221045
TI  - Spectral shaping of lasing in vertically aligned coupled nanowire lasers.
AB  - We use numerical simulations to study the effects of nanowire geometry on the
      emission spectra of nanowire-based lasers. The studied nanowire lasers are made
      from gallium-nitride and the simulations are performed using finite difference
      time domain method. We show that changes in the diameter of the nanowire lasers
      also change the effective refractive index of their optical guided modes, which
      allows control over their Fabry-Perot spectrum. In addition, we show that
      evanescent coupling of two vertically standing nanowire lasers, having different
      cross section sizes, leads to a Vernier effect, which results in single mode
      emission from the small footprint coupled lasers system.

PMID- 29221046
TI  - Design and fabrication of hybrid SPP waveguides for ultrahigh-bandwidth low
      penalty terabit-scale data transmission.
AB  - Here we design and fabricate a hybrid surface plasmon polarities (SPP) waveguide
      on the silicon-on-insulator (SOI) photonics platform. The designed hybrid SPP
      waveguide is composed of a metal ridge, an air gap, and a silicon ridge. We
      simulate the mode characteristics in the structure and design the waveguide with
      a wide air gap that can simplify the fabrication process and maintain the
      advantages of the hybrid SPP mode. The performance of ultrahigh-bandwidth data
      transmission through the proposed waveguide is then investigated using 161
      wavelength-division multiplexing (WDM) channels, each carrying a 11.2-Gbit/s
      orthogonal frequency-division multiplexing (OFDM) 16-ary quadrature amplitude
      modulation (16-QAM) signal. The bit-error rates (BERs) of all 161 channels are
      less than 1e-3. The favorable results show the prospect of on-chip optical
      interconnection using the proposed hybrid SPP waveguide.

PMID- 29221047
TI  - Shortcuts to adiabaticity in non-Hermitian quantum systems without rotating-wave
      approximation.
AB  - The technique of shortcuts to adiabaticity (STA) has attracted broad attention
      due to their possible applications in quantum information processing and quantum
      control. However, most studies published so far have been only focused on
      Hermitian systems under the rotating-wave approximation (RWA). In this paper, we
      propose a modified shortcuts to adiabaticity technique to realize population
      transfer for a non-Hermitian system without RWA. We work out an exact expression
      for the control function and present examples consisting of two-and three-level
      systems with decay to show the theory. The results suggest that the shortcuts to
      adiabaticity technique presented here is robust for fast passages. We also find
      that the decay has small effect on the population transfer in the three-level
      system. To shed more light on the physics behind this result, we reduce the
      quantum three-level system to an effective two-level one with large detunings.
      The shortcuts to adiabaticity technique of effective two-level system is studied.
      Thereby the high-fidelity population transfer can be implemented in non-Hermitian
      systems by our method, and it works even without RWA.

PMID- 29221048
TI  - Quantum memory and non-demolition measurement of single phonon state with
      nitrogen-vacancy centers ensemble.
AB  - In a diamond, the mechanical vibration-induced strain can lead to interaction
      between the mechanical mode and the nitrogen-vacancy (NV) centers. In this work,
      we propose to utilize the strain-induced coupling for the quantum non-demolition
      (QND) single phonon measurement and memory in a diamond. The single phonon in a
      diamond mechanical resonator can be perfectly absorbed and emitted by the NV
      centers ensemble (NVE) with adiabatically tuning the microwave driving. An
      optical laser drives the NVE to the excited states, which have much larger
      coupling strength to the mechanical mode. By adiabatically eliminating the
      excited states under large detuning limit, the effective coupling between the
      mechanical mode and the NVE can be used for QND measurement of the single phonon
      state. Under realistic experimental conditions, we numerically simulate the
      scheme. It is found that the fidelity of the absorbing and emitting process can
      reach a much high value. The overlap between the input and the output phonon
      shapes can reach 98.57%.

PMID- 29221049
TI  - Resonant absorption of electromagnetic waves in transition anisotropic media.
AB  - We study the mode conversion and resonant absorption phenomena occurring in a
      slab of a stratified anisotropic medium, optical axes of which are tilted with
      respect to the direction of inhomogeneity, using the invariant imbedding theory
      of wave propagation. When the tilt angle is zero, mode conversion occurs if the
      longitudinal component of the permittivity tensor, which is the one in the
      direction of inhomogeneity in the non-tilted case, varies from positive to
      negative values within the medium, while the transverse component plays no role.
      When the tilt angle is nonzero, the wave transmission and absorption show an
      asymmetry under the sign change of the incident angle in a range of the tilt
      angle, while the reflection is always symmetric. We calculate the reflectance,
      the transmittance and the absorptance for several configurations of the
      permittivity tensor and find that resonant absorption is greatly enhanced when
      the medium from the incident surface to the resonance region is hyperbolic than
      when it is elliptic. For certain configurations, the transmittance and
      absorptance curves display sharp peaks at some incident angles determined by the
      tilt angle.

PMID- 29221050
TI  - Double-pattern triangular pulse width modulation technique for high-accuracy high
      speed 3D shape measurement.
AB  - Using 1-bit binary patterns for three-dimensional (3D) shape measurement has been
      demonstrated as being advantageous over using 8-bit sinusoidal patterns in terms
      of achievable speeds. However, the phase quality generated by binary pattern(s)
      typically are not high if only a small number of phase-shifted patterns are used.
      This paper proposes a method to improve the phase quality by representing each
      pattern with the difference of two binary patterns: the first binary pattern is
      generated by triangular pulse width modulation (TPWM) technique, and the second
      being pi shifted from the first pattern that is also generated by TPWM technique.
      The phase is retrieved by applying a three-step phase-shifting algorithm to the
      difference patterns. Through optimizing the modulation frequency of the
      triangular carrier signal, we demonstrate that a high-quality phase can be
      generated for a wide range of fringe periods (e.g., from 18 to 1140 pixels) with
      only six binary patterns. Since only 1-bit binary patterns are required for 3D
      shape measurement, this paper will present a real-time 3D shape measurement
      system that can achieve 30 Hz.

PMID- 29221051
TI  - Dual displacement resolution encoder by integrating single holographic grating
      sensor and heterodyne interferometry.
AB  - A novel encoder with dual displacement resolution is developed by integrating a
      multiple-grating-scale holographic displacement sensor and a heterodyne
      interferometer. With suitable arrangement of the measurement system, two
      effective grating pitches (0.41 MUm and 10.62 MUm) can be obtained and the
      theoretical sensitivities of them are 0.9  degrees /nm and 0.036  degrees /nm.
      Meanwhile, the best resolution of the proposed method can be estimated of 0.3 pm
      and 7.4 pm, respectively. Furthermore, displacement errors of the proposed method
      can be better than 0.2% for 1 mm displacement measurement. The experimental
      results showed that the proposed encoder provided high sensitivity, high
      resolution, and well against environmental disturbance.

PMID- 29221052
TI  - Real-time gas sensing based on optical feedback in a terahertz quantum-cascade
      laser.
AB  - We report on real-time gas sensing with a terahertz quantum-cascade laser (QCL).
      The method is solely based on the modulation of the external cavity length,
      exploiting the intermediate optical feedback regime. While the QCL is operated in
      continuous-wave mode, optical feedback results in a change of the QCL frequency
      as well as its terminal voltage. The first effect is exploited to tune the lasing
      frequency across a molecular absorption line. The second effect is used for the
      detection of the self-mixing signal. This allows for fast measurement times on
      the order of 10 ms per spectrum and for real-time measurements of gas
      concentrations with a rate of 100 Hz. This technique is demonstrated with a
      mixture of D2O and CH3OD in an absorption cell.

PMID- 29221053
TI  - Ultra-high-speed PLIF imaging for simultaneous visualization of multiple species
      in turbulent flames.
AB  - In order to obtain more detailed characteristics and information in highly
      turbulent flames, for a better understanding of the transient behavior of eddies
      in such flames, a measurement technique with sufficient temporal resolution is
      requested. However, the probing of species distributions relevant in combustion
      (e.g. OH, CH2O) with ultra-high-speed laser diagnostics still remains a
      challenge. Nd:YAG clusters commercially available can generate only 4-8 pulses,
      although with high laser energy. Systems based on a diode-pumped solid-state
      Nd:YAG laser combined with a dye laser produce only about 100 MUJ pulse energy at
      ultra-high repetition rates (>=50 kHz). Even more comprehensive information on
      the flame structure can be gained if simultaneous recording of multi-species is
      performed. In the present work, the development of the first ultra-high-speed
      diagnostic technique capable of simultaneous probing of hydroxyl radicals and
      formaldehyde distributions at a repetition rate of 50 kHz is outlined. This has
      been achieved by employing a burst laser pumped optical parametric oscillator
      system for the simultaneous detection of CH2O excited at 355 nm and OH-radicals
      excited at 283 nm, where the interference of scattering laser light can be
      avoided. The applicability of the proposed technique was demonstrated in a highly
      turbulent jet flame. Moreover, the presented improvement in terms of the number
      of consecutive images recorded with ultra-high-speed planar laser induced
      fluorescence imaging is significant. Due to the high temporal resolution, the
      movement of CH2O pocket enclosed by OH at the flame tip can be clearly captured.
      The transport velocity of the CH2O pocket was calculated and found to be in good
      agreement with previous LDV results.

PMID- 29221054
TI  - Is the Rayleigh-Sommerfeld diffraction always an exact reference for high speed
      diffraction algorithms?
AB  - In several areas of optics and photonics the behavior of the electromagnetic
      waves has to be calculated with the scalar theory of diffraction by computational
      methods. Many of these high-speed diffraction algorithms based on a fast-Fourier
      transformation are approximations of the Rayleigh-Sommerfeld-diffraction (RSD)
      theory. In this article a novel sampling condition for the well-sampling of the
      Riemann integral of the RSD is demonstrated, the fundamental restrictions due to
      this condition are discussed, it will be demonstrated that the restrictions are
      completely removed by a sampling below the Abbe resolution limit and a very
      general unified approach for applying the RSD outside its sampling domain is
      given.

PMID- 29221055
TI  - Metasurface Salisbury screen: achieving ultra-wideband microwave absorption.
AB  - The metasurfaces have recently been demonstrated to provide full control of the
      phase responses of electromagnetic (EM) wave scattering over subwavelength
      scales, enabling a wide range of practical applications. Here, we propose a
      comprehensive scheme for the efficient and flexible design of metasurface
      Salisbury screen (MSS) capable of absorbing the impinging EM wave in an ultra
      wide frequency band. We show that properly designed reflective metasurface can be
      used to substitute the metallic ground of conventional Salisbury screen for
      generating diverse resonances in a desirable way, thus providing large
      controllability over the absorption bandwidth. Based on this concept, we
      establish an equivalent circuit model to qualitatively analysis the resonances in
      MSS and design algorithms to optimize the overall performance of the MSS.
      Experiments have been carried out to demonstrate that the absorption bandwidth
      from 6 GHz to 30 GHz with an efficiency higher than 85% can be achieved by the
      proposal, which is apparently much larger than that of conventional Salisbury
      screen (7 GHz - 17 GHz). The proposed concept of MSS could offer opportunities
      for flexibly designing thin electromagnetic absorbers with simultaneously ultra
      wide bandwidth, polarization insensitivity, and wide incident angle, exhibiting
      promising potentials for many applications such as in EM compatibility, stealth
      technique, etc.

PMID- 29221056
TI  - Multiwavelength generation from multi-nonlinear optical process in a 2D PPLT.
AB  - We have demonstrated multi-wavelength generation in a nonlinear photonic crystals
      of lithium tantalate. The optical parametric generation leads to second harmonic
      generation, sum-frequency generation and other frequency conversion in a cascade
      process. These conversions are assisted by all the optical nonlinear process
      involving chi(2) and achieved by satisfying the quasi-phase matching conditions.

PMID- 29221057
TI  - Statistical model for speckle pattern optimization.
AB  - Image registration is the key technique of optical metrologies such as digital
      image correlation (DIC), particle image velocimetry (PIV), and speckle metrology.
      Its performance depends critically on the quality of image pattern, and thus
      pattern optimization attracts extensive attention. In this article, a statistical
      model is built to optimize speckle patterns that are composed of randomly
      positioned speckles. It is found that the process of speckle pattern generation
      is essentially a filtered Poisson process. The dependence of measurement errors
      (including systematic errors, random errors, and overall errors) upon speckle
      pattern generation parameters is characterized analytically. By minimizing the
      errors, formulas of the optimal speckle radius are presented. Although the
      primary motivation is from the field of DIC, we believed that scholars in other
      optical measurement communities, such as PIV and speckle metrology, will benefit
      from these discussions.

PMID- 29221058
TI  - Determination of dissipative Dyakonov surface waves using a finite element method
      based eigenvalue algorithm.
AB  - A full-vectorial finite element method is developed to analyze the surface waves
      propagating at the interface between two media which could be dissipative
      particularly. The dissipative wave possessing a complex-valued propagation
      constant can be determined precisely for any given propagation direction and thus
      the property of losses could be thoroughly analyzed. Besides, by applying a
      special characteristic of the implicit circular block matrix, we reduce the
      computational consumptions in the analysis. By utilizing this method, the
      Dyakonov surface wave (DSW) at the interface between a dielectric and a metal
      dielectric multilayered (MDM) structure which serves as a hyperbolic medium is
      discussed. Its propagation loss is smaller for larger period of the MDM structure
      but its field becomes less confined to the interface.

PMID- 29221059
TI  - Metallic Fresnel zone plate implemented on an optical fiber facet for super
      variable focusing of light.
AB  - We propose and investigate a metallic Fresnel zone plate (FZP/MFZP) implemented
      on a silver-coated optical fiber facet for super-variable focusing of light, the
      focal point of which can be drastically relocated by varying the wavelength of
      the incident light. We numerically show that when its nominal focal length is set
      to 20 MUm at 550 nm, its effective focal length can be tuned by ~13.7 MUm for 300
      nm change in the visible wavelength range. This tuning sensitivity is over 20
      times higher than that of a conventional silica-based spherical lens. Even with
      such high tuning sensitivity with respect to the incident wavelength change, the
      effective beam radius at the focal point is preserved nearly unchanged,
      irrespective of the incident wavelength. Then, we fabricate the proposed device,
      exploiting electron- and focused-ion-beam processes, and experimentally verify
      its super-variable focusing functionality at typical red, green, and blue
      wavelengths in the visible wavelength range, which is in good agreement with the
      numerical prediction. Moreover, we propose a novel MFZP structure that primarily
      exploits the surface-plasmon-polariton-mediated, extra-ordinary transmission
      effect. For this we make all the openings of an MFZP, which are determined by the
      fundamental FZP design formula, be partitioned by multi-rings of all-sub
      wavelength annular slits, so that the transmission of azimuthally polarized light
      is inherently prohibited, thereby leading to super-variable and selective
      focusing of radially polarized light. We design and fabricate a proof-of
      principle structure implemented on a gold-coated fused-silica substrate, and
      verify its novel characteristics both numerically and experimentally, which are
      mutually in good agreement. We stress that both the MFZP structures proposed here
      will be very useful for micro-machining, optical trapping, and biomedical
      sensing, in particular, which invariably seek compact, high-precision, and
      flexible focusing schemes.

PMID- 29221060
TI  - Active metasurface modulator with electro-optic polymer using bimodal plasmonic
      resonance.
AB  - Electrically tunable metasurfaces have gained special interest as they can
      realize ultrathin surface-normal modulators in planar geometries. In this paper,
      we demonstrate a novel metasurface modulator based on electro-optic (EO) polymer
      that utilizes bimodal resonance inside a metallic subwavelength grating to
      increase the modulation efficiency. When two metal-insulator-metal (MIM) resonant
      modes are excited simultaneously inside the grating, they couple strongly to
      generate a sharp dip in the reflected spectrum. As a result, efficient intensity
      modulation with 15-dB extinction ratio can be obtained at the resonant wavelength
      under a small refractive index change of 8.5 * 10-3, corresponding to modulation
      voltage of less than 10 V. Due to the low parasitic capacitance of EO polymer and
      high conductivity of metallic gratings which is also used as the electrodes, the
      RC bandwidth of the device should easily exceed 100 GHz, potentially applicable
      to high-speed surface-normal modulators.

PMID- 29221061
TI  - Design of binary phase filters for depth-of-focus extension via binarization of
      axisymmetric aberrations.
AB  - We present a novel design approach for a binary phase mask with depth-of-focus
      (DoF) extension ability. Our method considers that the binarized version of an
      axisymmetric continuous phase pupil generates twin-intensity profiles that are
      symmetric with respect to the focal plane, each of which resembles the focal
      behavior of its continuous original. The DoF extension is realized by
      repositioning and coherently summing the twin foci to achieve an elongated focus
      along the axial direction. The shift of the two foci towards the focal plane can
      be handled by superimposing the defocus term in the continuous pupil function. We
      demonstrate our proposed design approach for two representative axisymmetric
      aberration functions, i.e., defocused phase axicon and spherical aberration. The
      manipulation of topological parameters in the phase axicon and spherical
      aberration, along with the defocus strength, enables the multiple binary phase
      filter designs of DoF extension of 3.2-7.1 fold with a phase axicon and 2.8-14.8
      fold with a spherical aberration, compared to the case with a clear aperture.

PMID- 29221062
TI  - Demonstration of a highly subluminal laser with suppression of cavity length
      sensitivity by nearly three orders of magnitude.
AB  - We have demonstrated a laser in which the frequency shift due to small cavity
      fluctuations is far less than what would be expected from a conventional laser.
      The factor of sensitivity suppression is inferred to be equal to the effective
      group index experienced by the laser, implying that this laser is subluminal. We
      have observed a suppression factor as high as 663. Such a laser is highly self
      stabilized compared to a conventional laser, and is expected to have a far
      smaller Schawlow-Townes linewidth. As a result, this laser may have potentially
      significant applications in the fields of high-precision optical metrology and
      passive frequency stabilization.

PMID- 29221063
TI  - 200 Gb/s transmission using a dual-polarization O-Band silicon photonic intensity
      modulator for Stokes vector direct detection applications.
AB  - We present a dual-polarization O-band silicon photonic (SiP) transmitter for
      intra-datacenter optical interconnects. The transmitter is built using two
      identical O-band traveling wave Mach-Zehnder modulators with an average VpiL and
      a bandwidth at 1.5 V bias voltage of 2.88 V.cm and 24.5 GHz, respectively. We
      experimentally demonstrate the transmitter in a Stokes vector direct-detection
      (SV-DD) system for dual-polarization intensity modulated signals with 2-level and
      4-level pulse amplitude modulation (DP-PAM2 and DP-PAM4) formats. The direct
      detection Stokes vector receiver (DD-SVR) followed by offline digital signal
      processing (DSP) is implemented for SOP de-rotation. We characterize the
      performance of the SV-DD system versus number of taps, received signal power,
      state of polarization (SOP), reach, and bit rate. Results reveal that 112 Gb/s DP
      PAM2 can be transmitted over 10 km of single mode fiber (SMF) at a bit error rate
      (BER) below 10-5 at -1 dBm received signal power irrespective of the SOP.
      Moreover, a 168 Gb/s (42 Gbaud) DP-PAM4 signal can be transmitted over 2 km and
      10 km at a BER below the 7% hard-decision forward error correction (HD-FEC)
      threshold (i.e., 3.8 * 10-3) at 0 dBm and 2 dBm, respectively. Furthermore, 224
      Gb/s and 200 Gb/s DP-PAM4 are successfully received at a BER below the HD-FEC in
      the back-to-back and 2 km cases, respectively. Finally, we compare the
      performance of the 6 * 2 multiple-input multiple-output (MIMO) equalization to a
      simpler 4 * 2 MIMO equalization and explain the superior performance of the 6 * 2
      in the presence of SVR imperfections.

PMID- 29221064
TI  - Nanoimprinted perovskite metasurface for enhanced photoluminescence.
AB  - Recently, solution-processed hybrid halide perovskite has emerged as promising
      materials for advanced optoelectronic devices such as photovoltaics,
      photodetectors, light emitting diodes and lasers. In the mean time, all
      dielectric metasurfaces with high-index materials have attracted attention due to
      their low-loss and high-efficient optical resonances. Because of its tunable by
      composition band gap in the visible frequencies, organolead halide perovskite
      could serve as a powerful platform for realizing high-index, low-loss
      metasurfaces. However, direct patterning of perovskite by lithography-based
      technique is not feasible due to material instability under moisture. Here we
      report novel organolead halide perovskite metasurfaces created by the cost
      effective thermal nanoimprint technology. The nanoimprinted perovskite
      metasurface showed improved surface morphology and enhanced optical absorption
      properties. Significantly enhanced optical emission with an eight-fold
      enhancement in photoluminescence (PL) intensity was observed under room
      temperature. Temperature-dependent PL of perovskite nanograting metasurface was
      also investigated. Based on our results, we believe that thermal nanoimprint is a
      simple and cost-effective technique to fabricate perovskite-based metasurfaces,
      which could have broad impact on optoelectronic and photonic applications.

PMID- 29221065
TI  - Spatial algebraic solitons at the Dirac point in optically induced nonlinear
      photonic lattices.
AB  - The discovery of a new type of soliton occurring in periodic systems is reported.
      This type of nonlinear excitation exists at a Dirac point of a photonic band
      structure, and features an oscillating tail that damps algebraically. Solitons in
      periodic systems are localized states traditionally supported by photonic
      bandgaps. Here, it is found that besides photonic bandgaps, a Dirac point in the
      band structure of triangular optical lattices can also sustain solitons. Apart
      from their theoretical impact within the soliton theory, they have many potential
      uses because such solitons are possible in both Kerr material and photorefractive
      crystals that possess self-focusing and self-defocusing nonlinearities. The
      findings enrich the soliton family and provide information for studies of
      nonlinear waves in many branches of physics.

PMID- 29221066
TI  - Sub-50 ps pulses at 620 nm obtained from frequency doubled 1240 nm diamond Raman
      laser.
AB  - We report a monolithic 1240 nm diamond Raman laser producing pulses with duration
      of 42-62 ps at 100 kHz repetition rate, and maximum average power of 246 mW. The
      Raman laser is formed by a 0.5-mm thick planar diamond, coated on both sides and
      pumped by ~100 ps pulses from a Q-switched 1064 nm laser. The maximum conversion
      efficiency from 1064 nm to 1240 nm was about 25%. The 1240 nm signal was
      frequency-doubled in single-pass configuration through a 10-mm long LBO crystal,
      enabling generation of pulses with a duration of 29-46 ps at 620 nm. The maximum
      average power at 620 nm was 128 mW, and the maximum conversion efficiency from
      1240 nm to 620 nm was 50%. The Raman laser provides an efficient and flexible way
      to extend short pulse operation to wavelengths in spectral domains difficult to
      reach, such as 620 nm and in addition provides a simple pulse shortening
      mechanisms.

PMID- 29221067
TI  - Robust 6-DOF motion sensing for an arbitrary rigid body by multi-view laser
      Doppler measurements.
AB  - We propose a novel method for the robust, non-contact, and six degrees of freedom
      (6-DOF) motion sensing of an arbitrary rigid body using multi-view laser Doppler
      measurements. The proposed method reconstructs the 6-DOF motion from fragmentary
      velocities on the surface of the target. It is unique compared to conventional
      contact-less motion sensing methods since it is robust against lack-of-feature
      objects and environments. By discussing the formulation of motion reconstruction
      by fragmentary velocities, we show that at least three viewpoints are essential
      for 6-DOF motion reconstruction. Further, we claim that the condition number of
      the measurement matrix can be a measure of system accuracy, and numerical
      simulation is performed to find an appropriate system configuration. The proposed
      method was implemented using a laser Doppler velocimeter, a galvanometer scanner,
      and some mirrors. We introduce the methods for calibration, coordinate system
      selection, and the calculation pipeline, all of which contribute to the accuracy
      of the proposed system. For evaluation, the proposed system is compared with an
      off-line chessboard-tracking scheme of a 500 fps camera. Experiments of measuring
      six different motion patterns are demonstrated to show the robustness of the
      proposed method against different kinds of motion. We also conduct evaluations
      with different distances and velocities. The mean value error is less than 1.3
      deg/s in rotation and 3.2 mm/s in translation, and is robust against changes in
      distance and velocity. For speed evaluation, the throughput of the proposed
      method is approximately 250 Hz and the latency is approximately 20 ms.

PMID- 29221068
TI  - Breakdown flash at telecom wavelengths in InGaAs avalanche photodiodes.
AB  - Quantum key distribution (QKD) at telecom wavelengths (1260 - 1625 nm) has the
      potential for fast deployment due to existing optical fibre infrastructure and
      mature telecom technologies. At these wavelengths, Indium Gallium Arsenide
      (InGaAs) avalanche photodiode (APD) based detectors are the preferred choice for
      photon detection. Similar to their Silicon counterparts used at shorter
      wavelengths, they exhibit fluorescence from recombination of electron-hole pairs
      generated in the avalanche breakdown process. This fluorescence may open side
      channels for attacks on QKD systems. Here, we characterize the breakdown
      fluorescence from two commercial InGaAs single photon counting modules, and find
      a spectral distribution between 1000 nm and 1600 nm. We also show that by
      spectral filtering, this side channel can be efficiently suppressed.

PMID- 29221069
TI  - Transmission line metamaterials based on strongly coupled split
      ring/complementary split ring resonators.
AB  - We experimentally studied the coupling between a double split ring resonator and
      a complementary split ring resonator. The greatest coupling occurs when the two
      resonators are separated by the average ring radius, and the dimensionless
      coupling is as large as 0.1, allowing a novel planar metamaterial based on this
      hybrid structure. The coupling strength can be varied up to a factor of 2 by
      changing the relative orientation of the split ring resonators. A 2*2 waveguide
      structure with -10 dB coupling factor can be achieved, and showing multi-mode
      plasmon-induced transparency. It can be considered one-dimensional metamaterials
      exhibiting negative permeability and permittivity simultaneously.

PMID- 29221070
TI  - Suppression of thermal wavelength drift in widely tunable DS-DBR laser for fast
      channel-to-channel switching.
AB  - We present a simple and effective method for suppressing thermally induced
      wavelength drift in a widely tunable digital supermode distributed Bragg
      reflector (DS-DBR) laser monolithically integrated with a semiconductor optical
      amplifier (SOA). For fast thermal compensation, pre-compensatory currents are
      injected into the gain medium section of the DS-DBR laser and the SOA. This
      method can be easily applied to existing commercial tunable lasers, since it is
      implemented without any modification to manufacturing process. Experimental
      results exhibit that wavelength stability is noticeably improved to +/- 0.01 nm.
      We also experimentally demonstrate a fast channel-to-channel switching in a
      wavelength-routed optical switching system employing a 90 * 90 arrayed waveguide
      grating router (AWGR). The measured switching time is less than 0.81 us.

PMID- 29221071
TI  - Ultrafast layer based computer-generated hologram calculation with sparse
      template holographic fringe pattern for 3-D object.
AB  - In this paper, we propose a new ultrafast layer based CGH calculation that
      exploits the sparsity of hologram fringe pattern in 3-D object layer.
      Specifically, we devise a sparse template holographic fringe pattern. The
      holographic fringe pattern on a depth layer can be rapidly calculated by adding
      the sparse template holographic fringe patterns at each object point position.
      Since the size of sparse template holographic fringe pattern is much smaller than
      that of the CGH plane, the computational load can be significantly reduced.
      Experimental results show that the proposed method achieves 10-20 msec for
      1024x1024 pixels providing visually plausible results.

PMID- 29221072
TI  - In-service crosstalk monitoring, tracing and lightpath re-optimization for space
      division multiplexing optical networks.
AB  - In recent years, to enlarge the single-mode fibers (SMFs) transmission capacity,
      researchers focused on the dimension of space, which is a new degree of freedom
      that is being considered for optical fiber communication beyond WDM. Space
      division multiplexing (SDM), including mode-division multiplexing (MDM) using
      multimode fibers (MMFs) or few-mode fibers (FMFs), and core multiplexing using
      multicore fibers (MCFs), has attracted much recent attention. In an SDM system,
      high-density spatial channels are tightly packed into a single fiber, thus making
      crosstalk among cores or modes a critical challenge due to fiber imperfections,
      bending, and twisting. Previous studies have mostly been confined to the routing
      algorithms for crosstalk reduction but few focuses on the in-service crosstalk
      monitoring, tracing and quality-of-transmission (QoT)-oriented lightpath re
      optimization. In this paper, we proposed novel in-service crosstalk monitoring
      and tracing (CMT) method and algorithm using fine-grained optical time slice
      monitoring channels for crosstalk reduction in SDM optical networks. Benefitting
      from the large amount of fine-grained channels provided by optical time slices,
      it becomes possible for every source node to allocate a dedicated monitoring time
      slice carrying the traffic and path information for each connection. Crosstalk
      monitoring and tracing can be realized by extracting the information contained in
      these monitoring time slices. Simulation results shows that the proposed CMT
      method and algorithm can obtain acceptable performance in large-scale network
      scenarios. Furthermore, we also proposed a quality-of-transmission (QoT)-oriented
      lightpath re-optimization mechanism based on in-service crosstalk monitoring and
      tracing to maintain a high level of QoT. Finally, we designed a prototype
      experiment to validate our proposed in-service crosstalk monitoring method.
      Results show that this method can realize in-service crosstalk monitoring,
      tracing and lightpath re-optimization over a seven-core fiber based transmission
      system, and the crosstalk with a minimum value of -37.9 dB can be monitored and
      successfully traced.

PMID- 29221073
TI  - Beyond Born-Rytov limit for super-resolution optical diffraction tomography.
AB  - Optical diffraction tomography (ODT) using Born or Rytov approximation suffers
      from severe distortions in reconstructed refractive index (RI) tomograms when
      multiple scattering occurs or the scattering signals are strong. These effects
      are usually seen as a significant impediment to the application of ODT because
      multiple scattering is directly linked to an unknown object itself rather than a
      surrounding medium, and a strong scatter invalidates the underlying assumptions
      of the Born and Rytov approximations. The focus of this article is to demonstrate
      for the first time that multiple scattering and high material contrast, if
      handled aptly, can significantly improve the image quality of the ODT thanks to
      multiple scattering inside a sample. Experimental verification using various
      phantom and biological cells substantiates that we not only revealed the
      structures that were not observable using the conventional approaches but also
      resolved the long-standing problem of missing cones in the ODT.

PMID- 29221074
TI  - Miniaturized calcium beam optical frequency standard using fully-sealed vacuum
      tube with 10-15 instability.
AB  - We implement a miniaturized calcium beam optical frequency standard using
      specially-designed fully-sealed vacuum tube, and realize the comparison with
      another calcium beam optical clock whose vacuum tube is sealed by flanges. The
      electron shelving detection method is adopted to improve the signal-to-noise
      ratio of the clock transition spectroscopy, and the readout laser is locked by
      modulation-free frequency locking technology based on Doppler effect. Injection
      locking is carried out to boost the power of the 657 nm master clock transition
      laser, thus ensuring the comparison. The fractional instability of the
      miniaturized calcium beam optical frequency standard using fully-sealed vacuum
      tube is 1.8*10-15 after 1600 s of averaging. Total volume of the system except
      for electronics is about 0.3 m3. To our knowledge, it's the first time to realize
      the optical frequency standard using fully-sealed vacuum tube. This work will
      promote the miniaturization and transportability of the optical clock based on
      atomic beam.

PMID- 29221075
TI  - Self-accelerating Airy-Laguerre-Gaussian light bullets in a two-dimensional
      strongly nonlocal nonlinear medium.
AB  - We report a self-accelerating wave packets eigenmode solution of a two
      dimensional (2D) nonlocal nonlinear Schrodinger equation (NNLSE) with an Airy
      beam time-dependence, and present their spatiotemporal profiles. The behaviours
      of such Airy-Laguerre-Gaussian light bullets, as propagated in a strongly
      nonlocal nonlinear medium (SNNM), are investigated both analytically and
      numerically. We found that the generation, control, and manipulation of the NL
      spatiotemporal light bullets are affected by the radial mode number and the
      azimuthal mode number, as well as the modulation depth. Our scheme is quite
      different from the linear light bullets, in which the wave propagates in a NL
      medium and is an eigenmode of NLSE.

PMID- 29221076
TI  - Temperature-insensitive frequency conversion by phase mismatch self-compensation
      in the same type of crystals.
AB  - Aiming at high-power laser frequency conversion, we present a new scheme that can
      self-compensate for the thermally induced phase mismatch. The basic design of the
      scheme is that three crystals with the same type are cascaded, of which the
      crystals at both ends are used for frequency conversion and the middle crystal is
      used for compensating phase mismatch. By configuring the polarization states of
      the interacting waves in the middle crystal, the sign of the first temperature
      derivative of the phase mismatch is opposite to that of the frequency conversion
      crystals. The thermally induced phase mismatch in the first crystal can thus be
      self-compensated in the middle crystal. To verify the utility of the proposed
      scheme, we experimentally demonstrated temperature-insensitive second and third
      harmonic generation using KH2PO4 crystals. The results show that the temperature
      acceptance bandwidth is about two times larger than that of using a single
      crystal. Since the crystals used are of the same type, this scheme has excellent
      universal applicability and is almost completely free from the limitations of the
      laser wavelength, crystal and phase-matching type. Therefore, the scheme can be
      widely applied to various frequency conversion processes and is scarcely any
      limitations.

PMID- 29221077
TI  - Selective area epitaxy of AlGaN nanowire arrays across nearly the entire
      compositional range for deep ultraviolet photonics.
AB  - Semiconductor light sources operating in the ultraviolet (UV)-C band (100-280 nm)
      are in demand for a broad range of applications but suffer from extremely low
      efficiency. AlGaN nanowire photonic crystals promise to break the efficiency
      bottleneck of deep UV photonics. We report, for the first time, site-controlled
      epitaxy of AlGaN nanowire arrays with Al incorporation controllably varied across
      nearly the entire compositional range. It is also observed that an Al-rich AlGaN
      shell structure is spontaneously formed, significantly suppressing nonradiative
      surface recombination. An internal quantum efficiency up to 45% was measured at
      room-temperature. We have further demonstrated large area AlGaN nanowire LEDs
      operating in the UV-C band on sapphire substrate, which exhibit excellent optical
      and electrical performance, including a small turn-on voltage of ~4.4 V and an
      output power of ~0.93 W/cm2 at a current density of 252 A/cm2. The controlled
      synthesis of AlGaN subwavelength nanostructures with well-defined size, spacing,
      and spatial arrangement and tunable emission opens up new opportunities for
      developing high efficiency LEDs and lasers and promises to break the efficiency
      bottleneck of deep UV photonics.

PMID- 29221078
TI  - Enhancement of the depth-of-field of integral imaging microscope by using
      switchable bifocal liquid-crystalline polymer micro lens array.
AB  - An integral imaging microscopy (IIM) system with improved depth-of-field (DoF)
      using a custom-designed bifocal polarization-dependent liquid-crystalline polymer
      micro lens array (LCP-MLA) is proposed. The implemented MLA has improved electro
      optical properties such as a small focal ratio, high fill factor, low driving
      voltage, and fast switching speed, utilizing a well-aligned reactive mesogen on
      the imprinted reverse shape of the lens and a polarization switching layer. A
      bifocal MLA switches its focal length according to the polarization angle and
      acquires different DoF information of the specimen. After two elemental image
      arrays are captured, the depth-slices are reconstructed and combined to provide a
      widened DoF. The fabricated bifocal MLA consists of two identical polarization
      dependent LCP-MLAs with 1.6 mm and f/16 focal ratio. Our experimental results
      confirmed that the proposed system improves the DoF of IIM without the need for
      mechanical manipulation.

PMID- 29221079
TI  - Quantitative analysis for the effect of the thermal physical property parameter
      of adhesive on the thermal performance of the quadrupolar fiber coil.
AB  - As a high-precision angular sensor, the fiber optic gyroscope (FOG) usually shows
      high sensitivity to disturbances of the environmental temperature. The thermal
      performance of the FOG will be directly affected by the selection of adhesive for
      adhesion inside the fiber coil, however, the current research on this is very
      rare. This paper is focusing the question above; firstly, the influence mechanism
      of temperature and stress on the non-reciprocity phase difference of the fiber
      coil is analyzed, and a model of fiber coil thermal-induced drift error is built.
      Secondly, the fiber coil three-dimensional simulation model including fiber core,
      coating layer, adhesive and various materials is built, and the accuracy of the
      model is verified by simulation and experiment. In the end, the influence of six
      thermal physical property parameters of adhesive material on the thermal
      performance of the FOG is analyzed quantitatively and the degree of influence
      from high to low is Young's modulus, Poisson's ratio, specific heat capacity,
      density and thermal conductivity. Results show that when choosing the adhesive,
      decreasing the thermal expansion coefficient, improving the young's modulus,
      reducing the poisson's ratio, reducing the heat capacity, reducing the density
      and increasing the thermal conductivity within a certain scope will be conducive
      to inhibit thermal-induced error of the FOG. And further prove that, the thermal
      stress distribution inside the fiber coil has more influence on the thermal
      performance of the FOG than the temperature field distribution. These findings
      are very helpful to chose and produce adhesive of fiber coil and improve the
      thermal performance of FOG.

PMID- 29221080
TI  - Integrated pillar scatterers for speeding up classification of cell holograms.
AB  - The computational power required to classify cell holograms is a major limit to
      the throughput of label-free cell sorting based on digital holographic
      microscopy. In this work, a simple integrated photonic stage comprising a
      collection of silica pillar scatterers is proposed as an effective nonlinear
      mixing interface between the light scattered by a cell and an image sensor. The
      light processing provided by the photonic stage allows for the use of a simple
      linear classifier implemented in the electric domain and applied on a limited
      number of pixels. A proof-of-concept of the presented machine learning technique,
      which is based on the extreme learning machine (ELM) paradigm, is provided by the
      classification results on samples generated by 2D FDTD simulations of cells in a
      microfluidic channel.

PMID- 29221081
TI  - Design and prototype of an augmented reality display with per-pixel mutual
      occlusion capability.
AB  - State-of-the-art optical see-through head-mounted displays for augmented reality
      (AR) applications lack mutual occlusion capability, which refers to the ability
      to render correct light blocking relationship when merging digital and physical
      objects, such that the virtual views appear to be ghost-like and lack realistic
      appearance. In this paper, using off-the-shelf optical components, we present the
      design and prototype of an AR display which is capable of rendering per-pixel
      mutual occlusion. Our prototype utilizes a miniature organic light emitting
      display coupled with a liquid crystal on silicon type spatial light modulator to
      achieve an occlusion capable AR display offering a 30 degrees  diagonal field of
      view and an angular resolution of 1.24 arcminutes, with an optical performance of
      > 0.4 contrast over the full field at the Nquist frequency of 24.2 cycles/degree.
      We experimentally demonstrate a monocular prototype achieving >100:1 dynamic
      range in well-lighted environments.

PMID- 29221082
TI  - Low temperature Voigt effect in the terbium gallium garnet crystal.
AB  - Magnetic linear birefringence and dichroism are investigated for the paramagnetic
      terbium gallium garnet (TGG) single crystal in the temperature range 8-100 K. The
      reciprocal nature is confirmed for the linear birefringence. Furthermore a
      theoretical model is validated that describes the intermixing of linear and
      circular birefringence. The ellipticity and rotation of the polarization ellipse
      are investigated in the light of these measurements. These otherwise minuscule
      magnetically induced effects are amplified at cryogenic temperatures and are
      determined by a phase-sensitive technique based on the Fourier decomposition of
      detected signal intensities. The correspondent measurements also allow us to
      determine the Curie-Weiss constant corroborating the presence of a magnetically
      frustrated spin system. Additionally we show how the Voigt geometry enables
      determining the direction of a magnetic field.

PMID- 29221083
TI  - Directly data processing algorithm for multi-wavelength pyrometer (MWP).
AB  - Data processing of multi-wavelength pyrometer (MWP) is a difficult problem
      because unknown emissivity. So far some solutions developed generally assumed
      particular mathematical relations for emissivity versus wavelength or emissivity
      versus temperature. Due to the deviation between the hypothesis and actual
      situation, the inversion results can be seriously affected. So directly data
      processing algorithm of MWP that does not need to assume the spectral emissivity
      model in advance is main aim of the study. Two new data processing algorithms of
      MWP, Gradient Projection (GP) algorithm and Internal Penalty Function (IPF)
      algorithm, each of which does not require to fix emissivity model in advance, are
      proposed. The novelty core idea is that data processing problem of MWP is
      transformed into constraint optimization problem, then it can be solved by GP or
      IPF algorithms. By comparison of simulation results for some typical spectral
      emissivity models, it is found that IPF algorithm is superior to GP algorithm in
      terms of accuracy and efficiency. Rocket nozzle temperature experiment results
      show that true temperature inversion results from IPF algorithm agree well with
      the theoretical design temperature as well. So the proposed combination IPF
      algorithm with MWP is expected to be a directly data processing algorithm to
      clear up the unknown emissivity obstacle for MWP.

PMID- 29221084
TI  - 2.38 Kbits/frame WDM transmission over a CVLC system with sampling reconstruction
      for SFO mitigation.
AB  - The camera-based visible light communication (CVLC) exploiting rolling shutter
      effect (RSE) is a cost-efficient technique that ensures secured data
      transmission. By controlling the on-off state of the light emitting diode (LED),
      data can be modulated onto the emitting visible light. The corresponding data
      recovery can be realized by exploiting the RSE of the mobile-phone camera. In
      this paper, based on a commercial RGB-LED and a single mobile-phone camera, a
      wavelength division-multiplexing (WDM) CVLC system exploiting RSE is
      experimentally demonstrated. For the generation and reception of the WDM signals,
      a structure of three parallel-independent channels is applied to the system. To
      mitigate the sampling frequency offset (SFO) effect, a low-complexity sampling
      reconstruction (SR) scheme is proposed and used in each channel of the system.
      Experimental results show that with the help of the proposed SR scheme, the
      system can achieve a theoretical data rate up to 2.38 Kbits/frame, with the bit
      error rate (BER) lower than 3.8 * 10-3.

PMID- 29221085
TI  - Compact single-etched sub-wavelength grating couplers for O-band application.
AB  - We demonstrate two single-etched sub-wavelength grating coupler (SWGC) designs
      for O-band application, one targeting at high coupling efficiency and the other
      targeting at broad operating bandwidth. The high-efficiency SWGC has a measured
      peak coupling efficiency of -3.8 dB and a 3-dB bandwidth of 40 nm, and the
      broadband SWGC has a measured peak coupling efficiency of -4.3 dB and a 3-dB
      bandwidth of 71 nm. Focusing gratings have been used in our SWGCs to reduce the
      design footprints and the dimensions of our SWGCs are smaller than 45 MUm * 24
      MUm. The back reflections of our SWGCs are suppressed to be below -15 dB over the
      wavelength range from 1260 nm to 1360 nm.

PMID- 29221086
TI  - Ultrasensitive terahertz sensing of gold nanoparticles inside nano slot antennas.
AB  - We introduce a robust control method of terahertz (THz) transmission by tuning
      filling factors of Au nanoparticles (AuNPs) inside nano slot antennas. AuNPs in
      sub-100 nm diameters were spread over the nano slot antennas, followed by
      sweeping them into the slots. AuNPs can be efficiently localized and inserted
      into nano slots where the THz fields are greatly enhanced, by a "squeegee" made
      of the polydimethylsiloxane (PDMS). The sweeping of the AuNPs results in further
      dramatic reduction of THz transmission by suppressing the fundamental resonance
      mode of the nano slot, as compared to a typical random dropping case. It
      definitely works for an accurate THz transmission control, as well as the removal
      of unwanted ions that occasionally confuse signal accuracy from the target
      signals. Our approach provides a complete reinterpretation of sample deposition
      for further steady demands in developing ultrasensitive terahertz (THz) molecule
      sensors.

PMID- 29221087
TI  - Scaling the abruptly autofocusing beams in the direct-space.
AB  - We propose a simple technique to scale the abruptly autofocusing beams in the
      direct space by introducing a scaling factor in the phase. Analytical formulas
      are deduced based on optical caustics, explicitly revealing how the scaling
      factor controls location, peak intensity, and size of the focal spot. We
      demonstrate that the multiplication of a scaling factor on the phase is
      equivalent to the axial-scaling transformation under the paraxial approximation.
      Further numerical and experimental results confirm theoretical predictions. In
      addition, amplitude modulation using phase-only holograms is used to maintain the
      peak intensity level of the focal spots.

PMID- 29221088
TI  - Tunable terahertz transmission properties of aligned Ni-nanowire arrays.
AB  - Aligned Ni nanowire (NW) arrays were investigated for terahertz (THz) wave
      modulation. By adjusting the NW density and order of the NW arrays, the resonant
      frequency and intensity of the THz waves can be effectively tuned. The tuning
      range of the resonant frequency is about 0.29 THz, and a transmittance of less
      than 40% in the frequency region from 0.5 to 2 THz is achieved by changing the NW
      density. Although the order of the NW arrays has no influence on the resonant
      frequency, the transmittance can be tuned about 21%. The ability to tune the
      intensity and resonant frequency effectively and the ease of fabrication of the
      Ni-NW arrays make them the potential candidates for THz tunable filters,
      intensity modulators, and spatial light modulators.

PMID- 29221089
TI  - Determination of complex Hermitian and anti-Hermitian interaction constants from
      a coupled photonic system via coherent control.
AB  - By manipulating the relative amplitude and phase between two incoming lights,
      coherent control of photonic systems can be realized. Here, we show by temporal
      coupled mode theory and finite-difference time-domain simulation that a coupled
      system can be actively controlled to exhibit plenty of different spectral,
      angular, and excitation behaviors. Electromagnetically induced transparency-like
      and Fano spectral characteristics as well as strong beam steering have been
      observed. Remarkably, by selectively exciting the coupled modes, we have
      developed a new approach to determine the complex Hermitian and anti-Hermitian
      interaction constants. We find the constants are strongly geometric and material
      dependent and they are of importance in understanding the non-Hermitian physics
      arising from the dissipative, open coupled system.

PMID- 29221090
TI  - Study of the momentum-resolved plasmonic field energy of Bloch-like surface
      plasmon polaritons from periodic nanohole array.
AB  - The angular surface plasmon mediated fluorescence from a two-dimensional Au
      nanohole array has been studied by reflectivity spectroscopy and Fourier-space
      photoluminescence microscopy. By using the rate equation model and temporal
      coupled mode theory, we determine the momentum-dependent coupling rate of light
      emitters to (-1,0) Bloch-like surface plasmon polaritons (SPPs) in the first
      Brillouin zone. The rate increases gradually when the SPPs propagate away from
      the Gamma-X direction and split into two at the Gamma-M point where two coupled
      modes are formed. In addition, both the spectral density-of-states (SDOS) and the
      plasmonic field energy are found to govern the momentum dependence. We also
      examine the behavior of the field energy as a function of the SPP propagation
      direction and it agrees well with the finite-difference time-domain simulations,
      showing the energy plays a major role in controlling the angular emission
      intensity. Our results devise a new method in studying the momentum-dependent
      plasmonic field energy and they are expected to provide insight in directional
      emission from periodic arrays.

PMID- 29221091
TI  - Raman lidar for hydrogen gas concentration monitoring and future radioactive
      waste management.
AB  - A multi-channel Raman lidar has been developed, allowing for the first time
      simultaneous and high-resolution profiling of hydrogen gas and water vapor. The
      lidar measures vibrational Raman scattering in the UV (355 nm) domain. It works
      in a high-bandwidth photon counting regime using fast SiPM detectors and takes
      into account the spectral overlap between hydrogen and water vapor Raman spectra.
      Measurement of concentration profiles of H2 and H2O are demonstrated along a 5
      meter-long open gas cell with 1-meter resolution at 85 meters. The instrument
      precision is investigated by numerical simulation to anticipate the potential
      performance at longer range. This lidar could find applications in the French
      project Cigeo for monitoring radioactive waste disposal cells.

PMID- 29221092
TI  - Structured light illumination for order sorting in Echelle spectrometers.
AB  - We report on the operation of an echelle spectrometer under structured light
      illumination. Each diffraction order of the spectrometer is encoded with a
      certain periodic structure allowing for order sorting by numerical analysis after
      detection. In contrast to cross-dispersed echelle spectrometers, in this approach
      the orders overlap at the detection plane so that the spectral calibration can be
      performed easily with a single reference wavelength. This operational
      simplification makes it possible to measure simultaneously the light source under
      study and the calibration wavelength giving rise to a self-calibrated echelle
      spectrometer. In this way the device compensates for the spectral drift due to
      temporal changes of environmental conditions in real time. Our proposal can be
      useful in a large number of applications requiring moderate, high or very high
      resolving power for a wide bandwidth in a non-isolated environment.

PMID- 29221093
TI  - Low-loss demonstration and refined characterization of silicon arrayed waveguide
      gratings in the near-infrared.
AB  - A resonator is characterized with two cascaded arrayed waveguide gratings (AWGs)
      in a ring formation. From this structure, the on-chip transmittance of a single
      AWG is extracted, independent of coupling efficiency. It provides improved
      measurement accuracy, which is essential for developing AWGs with extremely low
      loss. Previous methods normalize the off-chip AWG transmittance to that of a
      reference waveguide with identical coupling, leading to an uncertainty of ~14 %
      on the extracted on-chip AWG transmittance. It is shown here that the proposed
      "AWG-ring" method reduces this value to ~3 %. A low-loss silicon AWG and an AWG
      ring are fabricated. Channel losses with <2 dB are found, with a crosstalk per
      channel approaching -30 dB. Such an efficient wavelength multiplexing device is
      beneficial for the integration of spectroscopic sensors, multi-spectral lasers,
      and further progress in optical communication systems.

PMID- 29221094
TI  - Direct evidence of recombination between electrons in InGaN quantum discs and
      holes in p-type GaN.
AB  - Intense emission from an InGaN quantum disc (QDisc) embedded in a GaN nanowire p
      n junction is directly resolved by performing cathodoluminescence spectroscopy.
      The luminescence observed from the p-type GaN region is exclusively dominated by
      the emission at 380 nm, which has been usually reported as the emission from Mg
      induced impurity bands. Here, we confirm that the robust emission from 380 nm is
      actually not due to the Mg induced impurity bands, but rather due to being the
      recombination between electrons in the QDisc and holes in the p-type GaN. This
      identification helps to get a better understanding of the confused luminescence
      from nanowires with thin QDiscs embedded for fabricating electrically driven
      single photon emitters.

PMID- 29221095
TI  - Optimizing the performance of non-collinear optical parametric chirped pulse
      amplification via multi-pass structure based on two geometry configurations.
AB  - We propose a method for multi-pass non-collinear optical parametric chirped pulse
      amplification (MNOPCPA) based on two geometries, tangent phase-matching (TPM) and
      Poynting vector walk-off compensation (PVWC), which optimize the performance of
      optical parametric chirped pulse amplification (OPCPA). A feasible design scheme
      is also presented for use in implementing this approach. Employing this design,
      we construct and perform a numerical simulation, showing that back-conversion
      from the signal and idler to the pump can be inhibited, and that the conversion
      efficiency can be boosted dramatically, approaching the theoretical limit of
      ~64%, when amplification is nearly saturated at full bandwidth. In the MNOPCPA
      scheme, the output signal has a wider spectrum and a corresponding shorter
      Fourier-limited pulse duration with the pump being continuously depleted. A
      barycenter shift of the signal spot results from a spatial walk-off effect due to
      the pump, which can be offset and corrected well. To the best of our knowledge,
      this is the first demonstration of a multi-pass non-collinear OPCPA method
      employed the scheme of regenerative amplification.

PMID- 29221096
TI  - High resolution beam profiling of X-ray free electron laser radiation by polymer
      imprint development.
AB  - High resolution metrology of beam profiles is presently a major challenge at X
      ray free electron lasers. We demonstrate a characterization method based on beam
      imprints in poly (methyl methacrylate). By immersing the imprints formed at 47.8
      eV into organic solvents, the regions exposed to the beam are removed similar to
      resist development in grayscale lithography. This allows for extending the
      sensitivity of the method by more than an order of magnitude compared to the
      established analysis of imprints created solely by ablation. Applying the Beer
      Lambert law for absorption, the intensity distribution in a micron-sized focus
      can be reconstructed from one single shot with a high dynamic range, exceeding
      103. The procedure described here allows for beam characterization at free
      electron lasers revealing even faint beam tails, which are not accessible when
      using ablation imprint methods. We demonstrate the greatly extended dynamic range
      on developed imprints taken in focus of conventional Fresnel zone plates and
      spiral zone plates producing beams with a topological charge.

PMID- 29221097
TI  - High wall-plug efficiency blue III-nitride LEDs designed for low current density
      operation.
AB  - Commercial LEDs for solid-state lighting are often designed for operation at
      current densities in the droop regime (~35 A/cm2) to minimize costly chip area;
      however, many benefits can be realized by operating at low current density (J ~1 
      5 A/cm2). Along with mitigation of droop losses and reduction of the operating
      voltage, low J operation of LEDs opens the design space for high light extraction
      efficiency (LEE). This work presents detailed ray tracing simulations of an LED
      design for low J operation with LEE ~94%. The design is realized experimentally
      resulting in a peak wall-plug efficiency of 78.1% occurring at 3.45 A/cm2 and
      producing an output power of 7.2 mW for a 0.1 mm2 emitting area. At this
      operation point, the photon voltage Vp=hnuq exceeds the forward voltage (V),
      corresponding to a Vp/V = 103%.

PMID- 29221098
TI  - Pulse dynamics of dual-wavelength dissipative soliton resonances and domain wall
      solitons in a Tm fiber laser with fiber-based Lyot filter.
AB  - We report on the first demonstration of dual-wavelength square-wave pulses in a
      thulium-doped fiber laser. Under appropriate cavity parameters, dual-wavelength
      dissipative soliton resonances (DSRs) and domain wall solitons (DWSs) are
      successively obtained. Meanwhile, dark pulses generation is achieved at the dual
      wavelength DWSs region due to the overlap of the two domain wall pulses. The
      fiber-based Lyot filter, conducted by inserting PMF between an in-line PBS and a
      PD-ISO, facilitates the generation of dual-wavelength operation. The polarization
      resolved investigation suggests that the cross coupling between two orthogonal
      polarization components in the high nonlinear fiber plays an important role in
      the square-wave pulses formation. The investigation may be helpful for further
      understanding the square-wave pulse formation and has potential in application
      filed of multi-wavelength pulsed fiber lasers.

PMID- 29221099
TI  - Design of a uniform-illumination binocular waveguide display with diffraction
      gratings and freeform optics.
AB  - Uniform illuminance over the expanded exit pupil is an important requirement for
      waveguide display systems with a wide field of view (FOV). To address this issue,
      we develop a monochromatic binocular waveguide display in this paper. Two surface
      relief diffraction gratings are designed as in-couplers and out-couplers. The
      parameters of the gratings are optimized to achieve uniform diffraction
      efficiency distributions over a broad angular range. The grating couplers enable
      the system to realize a diagonal FOV of 40 degrees . A freeform surface prism is
      designed as the projection optics. The diameters of the two exit pupils are 12 mm
      in the expanding direction at an eye relief of 19 mm.

PMID- 29221100
TI  - Automated detection of cloud and aerosol features with SACOL micro-pulse lidar in
      northwest China.
AB  - The detection of cloud and aerosols using a modified retrieval algorithm solely
      for a ground-based micropulse lidar (MPL) is presented, based on one-year data at
      the Semi-Arid Climate Observatory and Laboratory (SACOL) site (35.57 degrees N,
      104.08 degrees E, 1965.8 m), northwest of China, from March 2011 to February
      2012. The work not only identifies atmosphere particle layers by means of the
      range-dependent thresholds based on elastic scattering ratio and depolarization
      ratio, but also discriminates the detected layers by combining empirical
      thresholds of the atmosphere's thermodynamics states and scattering properties
      and continuous wavelet transform (CWT) analyses. Two cases were first presented
      in detail that demonstrated that the modified algorithm can capture atmosphere
      layers well. The cloud macro-physical properties including cloud base height
      (CBH), cloud geometrical thickness (CGT), and cloud fraction (CF) were then
      analyzed in terms of their monthly and seasonal variations. It is shown that the
      maximum/minimum CBHs were found in summer (4.66 +/- 1.95km)/autumn (3.34 +/-
      1.84km). The CGT in winter (1.05 +/- 0.43km) is slightly greater than in summer
      (0.99 +/- 0.44km). CF varies significantly throughout year, with the maximum
      value in autumn (0.68), and a minimum (0.58) in winter, which is dominated by
      single-layered clouds (81%). The vertical distribution of CF shows a bimodal
      distribution, with a lower peak between 1 and 4km and a higher one between 6and
      9km. The seasonal and vertical variations in CF are important for the local
      radiative energy budget.

PMID- 29221102
TI  - Liquid-crystal tunable color filters based on aluminum metasurfaces.
AB  - Designing color pixels using plasmonic nanostructures and metasurfaces has become
      a luring area of research in recent years. Here, we experimentally demonstrated
      the voltage tunability of a dynamic plasmonic color filter by using an aluminum
      grating integrated with the nematic liquid crystal (LC). Along with a typical
      substrate coated with rubbed polyimide film, the aluminum grating itself serves
      as a molecular alignment layer to form a twisted LC cell. This hybrid structure
      allows electrically controlled transmission color by applying the voltage. A
      significant spectral tunability of such a device has been demonstrated by
      applying the small voltage from 0 to 4 Vrms.

PMID- 29221101
TI  - Enhanced light-matter interactions in graphene-covered dielectric magnetic
      mirrors.
AB  - Enhanced interactions of light with graphene on the surface of a lossless
      dielectric magnetic mirror (DMM) are studied theoretically and experimentally in
      the visible range, where the DMM is composed of truncated dielectric photonic
      crystals (PCs). The absorption of graphene on the DMM was enhanced by about 4
      fold for the spectral range within the forbidden gap of PCs over a wide range of
      incidence angles for both transverse electric and transverse magnetic
      polarizations compared with that of free-standing graphene. Moreover, the
      enhanced local electric field on the DMM surface led to much better detection
      efficiencies of the photocurrent, Raman spectroscopy and enhanced third-harmonic
      generation of graphene. These results offer a new way to achieve an enhanced
      interaction of light with graphene and develop new compact graphene-based
      devices.

PMID- 29221103
TI  - Compensation of aberration in quantitative phase imaging using lateral shifting
      and spiral phase integration.
AB  - We present a simple and effective method to eliminate system aberrations in
      quantitative phase imaging. Using spiral phase integration, complete information
      about system aberration is calculated from three laterally shifted phase images.
      The present method is especially useful when measuring confluent samples in which
      acquisition of background area is challenging. To demonstrate validity and
      applicability, we present measurements of various types of samples including
      microspheres, HeLa cells, and mouse brain tissue. Working conditions and
      limitations are systematically analyzed and discussed.

PMID- 29221104
TI  - Accurate measurements of circular and residual linear birefringences of spun
      fibers using binary polarization rotators.
AB  - We present a method to accurately measure the birefringence properties of spun
      fibers using binary polarization rotators. By taking the advantages of binary
      polarization rotator in polarization analysis, we are able to simultaneously
      measure both the circular and linear birefringences in a spun fiber with high
      accuracy. We obtain the circular and the residual linear birefringences of the
      spun fiber as a function of temperature T to be 3.34 * 10-5-5.11 * 10-8T and 8.1
      * 10-6-1.19 * 10-8T, respectively, with the residual linear birefringence about 4
      times less than the circular birefringence. We find, for the first time with the
      best of authors' knowledge, that the circular and the residual linear
      birefringences in a spun fiber are highly linear with the temperature, with
      thermal coefficients of -5.11 * 10-8  degrees C-1 and -1.19 * 10-8 degrees C-1,
      respectively, and that the relative changes per  degrees C of the circular and
      residual linear birefringence are almost identical, with values of -0.152% and 
      0.147% respectively. We believe that the method and data presented in this paper
      will be beneficial for making high quality spun fibers, as well as high accuracy
      fiber optic current sensors.

PMID- 29221105
TI  - Examination of potassium diode pumped alkali laser using He, Ar, CH4 and C2H6 as
      buffer gas.
AB  - We examined the performance of a potassium diode pumped alkali laser (K DPAL)
      using He, Ar, CH4, C2H6 and a mixture of He and CH4 as a buffer gas to provide
      spin-orbit mixing of the 4P3/2 and 4P1/2 states of Potassium atoms. We found that
      pure helium cannot be used as an efficient buffer gas for continuous wave lasing
      without using a flowing system with a considerable flow speed of about 100 m/s.
      In contrast, using a small amount of methane (10-20 Torr) mixed with helium,
      continuous wave lasing can be achieved using very moderate flow speeds of about 1
      m/s.

PMID- 29221106
TI  - High sensitivity optical biosensor based on polymer materials and using the
      Vernier effect.
AB  - We demonstrate the fabrication of a Vernier effect SU8/PMATRIFE polymer optical
      biosensor with high homogeneous sensitivity using a standard photolithography
      process. The sensor is based on one micro-resonator embedded on each arm of a
      Mach-Zehnder interferometer. Measurements are based on the refractive index
      variation of the optical waveguide superstrate with different concentrations of
      glucose solutions. The sensitivity of the sensor has been measured as 17558
      nm/RIU and the limit of detection has been estimated to 1.1.10-6 RIU.

PMID- 29221107
TI  - Interferometric synthetic aperture microscopy for extended focus optical
      coherence microscopy.
AB  - Optical coherence microscopy (OCM) is an interferometric technique providing 3D
      images of biological samples with micrometric resolution and penetration depth of
      several hundreds of micrometers. OCM differs from optical coherence tomography
      (OCT) in that it uses a high numerical aperture (NA) objective to achieve high
      lateral resolution. However, the high NA also reduces the depth-of-field (DOF),
      scaling with 1/NA2. Interferometric synthetic aperture microscopy (ISAM) is a
      computed imaging technique providing a solution to this trade-off between
      resolution and DOF. An alternative hardware method to achieve an extended DOF is
      to use a non-Gaussian illumination. Extended focus OCM (xfOCM) uses a Bessel beam
      to obtain a narrow and extended illumination volume. xfOCM detects back-scattered
      light using a Gaussian mode in order to maintain good sensitivity. However, the
      Gaussian detection mode limits the DOF. In this work, we present extended ISAM
      (xISAM), a method combining the benefits of both ISAM and xfOCM. xISAM uses the
      3D coherent transfer function (CTF) to generalize the ISAM algorithm to different
      system configurations. We demonstrate xISAM both on simulated and experimental
      data, showing that xISAM attains a combination of high transverse resolution and
      extended DOF which has so far been unobtainable through conventional ISAM or
      xfOCM individually.

PMID- 29221108
TI  - Checkpoint and PARP inhibitors, for whom and when.

PMID- 29221109
TI  - Protein phosphatase 4 regulatory subunit 2 (PPP4R2) is recurrently deleted in
      acute myeloid leukemia and required for efficient DNA double strand break repair.
AB  - We have previously identified a recurrent deletion at chromosomal band 3p14.1-p13
      in patients with acute myeloid leukemia (AML). Among eight protein-coding genes,
      this microdeletion affects the protein phosphatase 4 regulatory subunit 2
      (PPP4R2), which plays an important role in DNA damage response (DDR).
      Investigation of mRNA expression during murine myelopoiesis determined that
      Ppp4r2 is higher expressed in more primitive hematopoietic cells. PPP4R2
      expression in primary AML samples compared to healthy bone marrow was
      significantly lower, particularly in patients with 3p microdeletion or complex
      karyotype. To identify a functional role of PPP4R2 in hematopoiesis and leukemia,
      we genetically inactivated Ppp4r2 by RNAi in murine hematopoietic stem and
      progenitor cells and murine myeloid leukemia. Furthermore, we ectopically
      expressed PPP4R2 in a deficient human myeloid leukemic cell line. While PPP4R2 is
      involved in DDR of both hematopoietic and leukemic cells, our findings indicate
      that PPP4R2 deficiency impairs de-phosphorylation of phosphorylated key DDR
      proteins KRAB-domain associated protein 1 (pKAP1), histone variant H2AX
      (gammaH2AX), tumor protein P53 (pP53), and replication protein A2 (pRPA2).
      Potential impact of affected DNA repair processes in primary AML cases with
      regard to differential PPP4R2 expression or 3p microdeletion is also supported by
      our results obtained by gene expression profiling and whole exome sequencing.
      Impaired DDR and increased DNA damage by PPP4R2 suppression is one possible
      mechanism by which the 3p microdeletion may contribute to the pathogenesis of
      AML. Further studies are warranted to determine the potential benefit of
      inefficient DNA repair upon PPP4R2 deletion to the development of therapeutic
      agents.

PMID- 29221110
TI  - A seven-gene signature predicts overall survival of patients with colorectal
      cancer.
AB  - Colorectal cancer (CRC) is a major cause of global cancer mortality. Gene
      expression profiles can help predict prognosis of patients with CRC. In most of
      previous studies, disease recurrence was analyzed as the survival endpoint. Thus
      we aim to build a robust gene signature for prediction of overall survival (OS)
      in patients with CRC. Fresh frozen CRC tissues from 64 patients were analyzed
      using Affymetrix HG-U133plus 2.0 gene arrays. By performing univariate survival
      analysis, 6487 genes were found to be associated with the OS in our cohort. KEGG
      analysis revealed that these genes were mainly involved in pathways such as
      endocytosis, axon guidance, spliceosome, Wnt signalling and ubiquitin mediated
      proteolysis. A seven-gene signature was further selected by a robust likelihood
      based survival modelling approach. The prognostic model of seven-gene signature
      (NHLRC3, ZDHHC21, PRR14L, CCBL1, PTPRB, PNPO, and PPIP5K2) was constructed and
      weighted by regression coefficient, which divided patients into high- and low
      risk groups. The OS for patients in high-risk group was significantly poorer
      compared with patients in low-risk group. Moreover, all seven genes were found to
      be differentially expressed in CRC tissues as compared with adjacent normal
      tissues, indicating their potential role in CRC initiation and progression. This
      seven-gene signature was further validated as an independent prognostic marker
      for OS prediction in patients with CRC in other two independent cohorts. In
      short, we developed a robust seven-gene signature that can predict the OS for CRC
      patients, providing new insights into identification of CRC patients with high
      risk of mortality.

PMID- 29221111
TI  - Nasopharyngeal carcinoma risk prediction via salivary detection of host and
      Epstein-Barr virus genetic variants.
AB  - Genetic susceptibility and Epstein-Barr virus (EBV) infection are important
      etiological factors in nasopharyngeal carcinoma (NPC). In this study, in southern
      China, where NPC is endemic, a single nucleotide polymorphism (SNP) in the EBV
      encoded RPMS1 gene (locus 155391: G > A [G155391A]) and seven host SNPs
      (rs1412829, rs28421666, rs2860580, rs2894207, rs31489, rs6774494, and rs9510787)
      were confirmed to be significantly associated with NPC risk in 50 NPC cases
      versus 54 hospital-based controls with throat washing specimens and 1925 NPC
      cases versus 1947 hospital-based controls with buffy coat samples, respectively.
      We established a strategy to detect the NPC-associated EBV and host SNPs using
      saliva samples in a single test that is convenient, noninvasive, and cost
      effective and displays good compliance. The potential utility of this strategy
      was tested by applying a risk prediction model integrating these EBV and host
      genetic variants to a population-based case-control study comprising 1026
      incident NPC cases and 1148 controls. Receiver operating characteristic (ROC)
      curve analysis revealed an area under the curve of the NPC risk prediction model
      of 0.74 (95% CI: 0.71-0.76). Net reclassification improvement (NRI) analysis
      showed that inclusion of the EBV SNP significantly improved the discrimination
      ability of the model (NRI = 0.30, P < 0.001), suggesting the promising value of
      EBV characteristics for identifying high-risk NPC individuals in endemic areas.
      Taken together, we developed a promising NPC risk prediction model via
      noninvasive saliva sampling. This approach might serve as a convenient and
      effective method for screening the population with high-risk of NPC.

PMID- 29221112
TI  - Traditional Chinese medicine Ka-Sai-Ping suppresses the growths of gastric
      cancers via induction of autophagy.
AB  - Traditional Chinese medication is increasingly used to treat a wide range of
      human chronic diseases like cardiovascular diseases and cancers. This study was
      designed to explore whether ka-sai-ping (KSP), a novel traditional Chinese
      medicine developed by us, prevents gastric cancer growths and to investigate the
      underlying mechanism. The xenograft model of mouse gastric cancer was established
      by injecting MFCs into nude mouse subcutaneously. Cell autophagy was assessed by
      MDC staining. Lysosome and mitochondria were detected by Lyso-Tracker Red and
      Mito-Traker Green staining. Incubation of cultured mouse gastric cancer cell line
      MFCs with KSP for 48 hours, concentration-dependently reduced cell survivals and
      activated autophagy, which were accompanied with damaged lysosomes and
      mitochondria. In vivo studies indicated that KSP therapy (20 ml/kg/day) for two
      weeks suppressed the growth of gastric cancer, increased the protein levels of
      LC3-II, beclin-1, cathepsin L, bcl-2, p53, and capase-3 in tumor tissues from the
      xenograft model of mouse gastric cancer. Importantly, all these effects induced
      by KSP were abolished by co-administration of autophagy inhibitor 3-MA. In
      conclusion, KSP activates cell autophagy to suppress gastric cancer growths.
      Clinically, KSP is potentially considered as a medicine to treat patients with
      gastric cancer.

PMID- 29221113
TI  - The peripheral immune status of granulocytic myeloid-derived suppressor cells
      correlates the survival in advanced gastric cancer patients receiving cisplatin
      based chemotherapy.
AB  - Background: The prognostic significance of peripheral immune status in patients
      with advanced gastric cancer (AGC) remains unclear. Results: From July 2013
      through December 2014, 37 patients were enrolled. Among patients with 25 subsets
      of immune cells, patients in the high group of granulocytic myeloid-derived
      suppressor cells (Gr-MDSCs) showed significantly shorter progression-free
      survival (PFS) than those in the low group (3.98 vs. 8.78 months; hazards ratio
      (HR), 2.61; p = 0.01). In multivariate analysis, the high Gr-MDSCs value was also
      associated with shorter PFS (HR, 4.60; 95% confidence interval (CI), 1.79-11.8; p
      = 0.001). Although significant difference was not found in univariate analysis,
      the high Gr-MDSCs group was associated with shorter overall survival (OS) (HR,
      2.89; 95% CI, 1.23-6.80; p = 0.015) in multivariate analysis. Materials and
      Methods: In this explorative prospective study, peripheral blood samples were
      collected from AGC patients before initiating first-line cisplatin-based
      chemotherapy (S-1 + cisplatin or S-1 + cisplatin + docetaxel). Peripheral blood
      mononuclear cells were analyzed for 25 immune subsets by multicolor flow
      cytometry. PFS and OS were compared between the patients divided into high and
      low (>= and < median, respectively) groups based on the median value for each
      immune cell subset. Conclusions: The peripheral immune status of Gr-MDSCs appears
      to affect the prognosis in AGC. Further research is needed to confirm the
      clinical value of the level of circulating Gr-MDSCs as a prognostic and/or
      predictive marker in AGC.

PMID- 29221114
TI  - Interferon-tau increases BoLA-I for implantation during early pregnancy in dairy
      cows.
AB  - Interferon-tau (IFN-tau) signals pregnancy recognition in ruminants. We
      investigated the effects of IFN-tau produced by embryo trophoblastic cells (ETCs)
      on expression of bovine leukocyte antigen-I (BoLA-I), a bovine analogue of human
      MHC-I, in endometrial luminal epithelial cells (EECs) during early pregnancy in
      dairy cows. Expression of IFN-tau and BoLA-I was increased in endometrial tissues
      during early pregnancy. Expression of the anti-inflammatory cytokine IL-10 was
      increased in endometrial tissues, while expression of the pro-inflammatory
      cytokine IL-6 was decreased, indicating immunosuppression. Progesterone increased
      IFN-tau expression in EECs. IFN-tau increased p-STAT1 and p-STAT3 levels in EECs,
      but reduced TRAF3 levels. In addition, IFN-tau increased expression of BoLA-I and
      IL-10, but decreased expression of IL-6 in EECs. These results indicate that IFN
      tau enables stable implantation in dairy cows by increasing expression of BoLA-I,
      and by immunosuppression mediated by increased IL-10 and decreased IL-6
      expression.

PMID- 29221115
TI  - lncRNA MALAT1, HOTTIP and PVT1 as predictors for predicting the efficacy of GEM
      based chemotherapy in first-line treatment of pancreatic cancer patients.
AB  - This study evaluated the lnc-RNAs as biomarker to predict efficacy of gemcitabine
      (GEM) based chemotherapy as the first-line treatment for locally advanced or
      advanced pancreatic cancer patients. We selected 62 patients with GEM based
      chemotherapy and divided two groups according to the PFS. We found that the
      expression of MALAT1, HOTTIP, and PVT1 in serum had a significant difference
      among the two groups. Furthermore, we estimated the PFS and response rate based
      on the expression levels of MALAT1, HOTTIP and PVT1. The response rate of two
      groups showed a significant difference according to the expression levels of
      MALAT1, HOTTIP and PVT1. Based on the expression levels of MALAT1, HOTTIP and
      PVT1, the response rate of high expression of PVT1 and low expression of PVT1 was
      respectively 14.8% and 37.1% and 18.2% (high HOTTIP group) and 37.9% (low HOTTIP
      group), 10.7%(high MALAT1 group) and 41.1% (low MALAT1 group). The PFS of
      patients with high and low expression levels PVT1 was 2.6 months and 4.0 months
      (p<0.001), respectively. The PFS of patients with high and low expression levels
      of HOTTIP was 2.7 months and 4.1 months (p<0.001), respectively, and the PFS of
      patients with high and low expression levels of MALAT1 was 3.0 months and 3.7
      months (P=0.026), respectively. The results suggest that MALAT1, HOTTIP and PVT1
      as predictors to predict the efficacy of GEM based chemotherapy in first-line
      treatment of pancreatic cancer patients.

PMID- 29221116
TI  - The addition of abemaciclib to sunitinib induces regression of renal cell
      carcinoma xenograft tumors.
AB  - Multiple therapies currently exist for renal cell carcinoma, however, most do not
      result in cure and the development of acquired resistance is the rule rather than
      the exception. CDK4/6 and PIM1 kinases are potential new therapeutic targets in
      RCC. Abemaciclib is a potent CDK4/6 and PIM1 kinase inhibitor, thus we evaluated
      the effects of abemaciclib on renal cell carcinoma. In vitro, abemaciclib causes
      decreased cellular viability, increased apoptosis, and alterations in autophagy
      in renal cell carcinoma cell lines. A pre-clinical mouse model of RCC shows
      abemaciclib in combination with sunitinib to cause dramatic reduction in tumor
      sizes without overt toxicity. Thus abemaciclib is active in renal cell carcinoma
      and should be evaluated in a clinical trial in combination with sunitinib.
      Additionally, CDK4/6 and PIM1 kinase appear to be viable clinical targets in
      renal cell carcinoma.

PMID- 29221117
TI  - Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity
      and cell viability in vitro and impairs tumor growth in vivo.
AB  - Pro-inflammatory cells, cytokines, and chemokines are essential in promoting a
      tumor supporting microenvironment. Chemerin is a chemotactic protein and a
      natural ligand for the receptors CMKLR1, GPR1, and CCRL2. The chemerin/CMKLR1
      axis is involved in immunity and inflammation, and it has also been implicated in
      obesity and cancer. In neuroblastoma, a childhood tumor of the peripheral nervous
      system we identified correlations between high CMKLR1 and GPR1 expression and
      reduced overall survival probability. CMKLR1, GPR1, and chemerin RNA and protein
      were detected in neuroblastoma cell lines and neuroblastoma primary tumor tissue.
      Chemerin induced calcium mobilization, increased MMP-2 synthesis as well as MAP
      kinase- and Akt-mediated signaling in neuroblastoma cells. Stimulation of
      neuroblastoma cells with serum, TNFalpha or IL-1beta increased chemerin
      secretion. The small molecule CMKLR1 antagonist alpha-NETA reduced the
      clonogenicity and viability of neuroblastoma cell lines indicating the
      chemerin/CMKLR1 axis as a promoting factor in neuroblastoma tumorigenesis.
      Furthermore, nude mice carrying neuroblastoma SK-N-AS cells as xenografts showed
      impaired tumor growth when treated daily with alpha-NETA from day 1 after tumor
      cell injection. This study demonstrates the potential of the chemerin/CMKLR1 axis
      as a prognostic factor and possible therapeutic target in neuroblastoma.

PMID- 29221118
TI  - Lentinan dose dependence between immunoprophylaxis and promotion of the murine
      liver cancer.
AB  - Lentinan could exhibit significant biological activity favorable for human health
      and disease control such as the recovery of patients with liver cancer. In order
      to investigate the effect of lentinan dose dependence between immunoprophylaxis
      and promotion of cancer cell proliferation of the murine liver cancer, different
      concentrations of lentinan were prepared for the test in vitro (MTT assay) and in
      vivo (cumulative survival assay, spleen lymphocyte proliferation tests and
      peritoneal macrophage phagocytosis assays). New emerging proteins of the H22 cell
      incubated with lentinan was demonstrated by MS analysis and protein database
      searching. Lentinan was non-toxic for HL7702 cells but inhibited H22 cells
      proliferation obviously in a dose-dependent manner. In vivo, the proliferation of
      H22 hepatocarcinoma cells was inhibited by lentinan 0.4mg/kg body weight (L2,
      survival rate, 20%, PPP<0.01). Six proteins 60Sacidic ribosomal protein P2,
      Peroxiredoxin-2, Annexin A5, PDZ and LIM domain protein 1, Src substrate
      cortactin and Moesin were found as emerging proteins of the H22 cell incubated
      with high dose lentinan which related to cancer promotion closely. In conclusion,
      Thelentinan was relatively safe and could inhibit the proliferation of H22 cancer
      cells through immunity improvement when it's intake was in proper quantity.

PMID- 29221119
TI  - Analysis of NPM1 splice variants reveals differential expression patterns of
      prognostic value in acute myeloid leukemia.
AB  - Mutations of the nucleophosmin-1 (NPM1) gene in cytogenetically normal (CN) acute
      myeloid leukemia (AML) identify a group of patients with more favorable
      prognosis. NPM1 encodes three main alternatively spliced isoforms R1(B23.1),
      R2(B23.2), and R3(B23.3). The expression of splice variants R1, R2 and R3 were
      higher in AML patients compared to normal cells of healthy volunteers (HVs),
      although RNA-seq analysis revealed enhanced R2 expression also in less
      differentiated cells of HVs as well as in AML cells. The variant R2, which lacks
      exons 11 and 12 coding for the nucleolar localization domain, might behave
      similar to the mutant form of NPM1 (NPM1mut). In accordance, in CN-AML high R2
      expression was associated with favorable impact on outcome. Moreover, functional
      studies showed nucleolar localization of the eGFP-NPM1 wildtype and cytoplasmic
      localization of the eGFP-NPM1 mut protein. While the eGFP-NPM1 R2 splice variant
      localized predominantly in the nucleoplasm, we also could detect cytoplasmic
      expression for the R2 variant. These results support a unique biological
      consequence of R2 overexpression and in part explain our clinical observation,
      where that high R2 variant expression was associated with a better prognosis in
      CN-AML patients.

PMID- 29221120
TI  - Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma
      patients in China.
AB  - Pancreatic carcinoma (PC) is a lethal cancer. Gut microbiota is associated with
      some risk factors of PC, e.g. obesity and types II diabetes. However, the
      specific gut microbial profile in clinical PC in China has never been reported.
      This prospective study collected 85 PC and 57 matched healthy controls (HC) to
      analyze microbial characteristics by MiSeq sequencing. The results showed that
      gut microbial diversity was decreased in PC with an unique microbial profile,
      which partly attributed to its decrease of alpha diversity. Microbial alterations
      in PC featured by the increase of certain pathogens and lipopolysaccharides
      producing bacteria, and the decrease of probiotics and butyrate-producing
      bacteria. Microbial community in obstruction cases was separated from the un
      obstructed cases. Streptococcus was associated with the bile. Furthermore, 23
      microbial functions e.g. Leucine and LPS biosynthesis were enriched, while 13
      functions were reduced in PC. Importantly, based on 40 genera associated with PC,
      microbial markers achieves a high classification power with AUC of 0.842. In
      conclusion, gut microbial profile was unique in PC, providing a microbial marker
      for non-invasive PC diagnosis.

PMID- 29221121
TI  - Tropomyosin isoform Tpm2.1 regulates collective and amoeboid cell migration and
      cell aggregation in breast epithelial cells.
AB  - Metastasis dissemination is the result of various processes including cell
      migration and cell aggregation. These processes involve alterations in the
      expression and organization of cytoskeletal and adhesion proteins in tumor cells.
      Alterations in actin filaments and their binding partners are known to be key
      players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a
      common characteristic of transformed cells. In this study, we examined the role
      of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and
      cell aggregation, because this isoform is downregulated in primary and metastatic
      breast cancer as well as various breast cancer cell lines. Downregulation of
      Tpm2.1 using siRNA or shRNA resulted in retardation of collective cell migration
      but increase in single cell migration and invasion. Loss of Tpm2.1 is associated
      with enhanced actomyosin contractility and increased expression of E-cadherin and
      beta-catenin. Furthermore, inhibition of Rho-associated kinase (ROCK) recovered
      collective cell migration in Tpm2.1-silenced cells. We also found that Tpm2.1
      silenced cells formed more compacted spheroids and exhibited faster cell motility
      when spheroids were re-plated on 2D surfaces coated with fibronectin and
      collagen. When Tpm2.1 was downregulated, we observed a decrease in the level of
      AXL receptor tyrosine kinase, which may explain the increased levels of E
      cadherin and beta-catenin. These studies demonstrate that Tpm2.1 functions as an
      important regulator of cell migration and cell aggregation in breast epithelial
      cells. These findings suggest that downregulation of Tpm2.1 may play a critical
      role during tumor progression by facilitating the metastatic potential of tumor
      cells.

PMID- 29221122
TI  - Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate
      dehydrogenase inhibition.
AB  - Reduction in nucleotide pools through the inhibition of mitochondrial enzyme
      dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce
      cancer cell proliferation and tumour growth. The current study sought to
      investigate whether this antiproliferative effect could be enhanced by combining
      Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor
      teriflunomide was more selective towards transformed mouse embryonic fibroblasts
      than their primary or immortalised counterparts, and this effect was amplified
      when cells were subsequently exposed to PF477736 Chk1 inhibitor. Flow cytometry
      analyses revealed substantial accumulations of cells in S and G2/M phases,
      followed by increased cytotoxicity which was characterised by caspase 3-dependent
      induction of cell death. Associating PF477736 with teriflunomide also
      significantly sensitised SUM159 and HCC1937 human triple negative breast cancer
      cell lines to dihydroorotate dehydrogenase inhibition. The main characteristic of
      this effect was the sustained accumulation of teriflunomide-induced DNA damage as
      cells displayed increased phospho serine 139 H2AX (gammaH2AX) levels and
      concentration-dependent phosphorylation of Chk1 on serine 345 upon exposure to
      the combination as compared with either inhibitor alone. Importantly a similar
      significant increase in cell death was observed upon dual siRNA mediated
      depletion of Chk1 and DHODH in both murine and human cancer cell models.
      Altogether these results suggest that combining DHODH and Chk1 inhibitions may be
      a strategy worth considering as a potential alternative to conventional
      chemotherapies.

PMID- 29221124
TI  - Production of Nalpha-acetyl Talpha1-HSA through in vitro acetylation by RimJ.
AB  - Thymosin alpha 1 (Talpha1) is an important immunomodulating agent with various
      clinical applications. The natural form of Talpha1 is Nalpha -acetylated, which
      was supposed to be related to in vivo stability of the hormone. In this study,
      fusion protein Talpha1-HSA was constructed and expressed in Pichia pastoris.
      RimJ, a Nalpha -acetyltransferase from E.coli, was also overexpressed and
      purified to homogeneity. In vitro acetylation of Talpha1-HSA in the presence of
      RimJ and acetyl coenzyme A resulted in Nalpha -acetyl Talpha1-HSA. The Nalpha 
      acetylation was determined by LC-MS/MS. Kinetic assay indicated that RimJ had a
      higher affinity to desacetyl Talpha1 than to Talpha1-HSA. Bioactivity assay
      revealed fully retained activity of Talpha1 when the hormone was connected to the
      N-terminus of the fusion protein, while the activity was compromised in our
      previously constructed HSA-Talpha1. With fully retained activity and N-terminal
      acetylation, Nalpha -acetyl Talpha1-HSA was expected to be a more promising
      pharmaceutical agent than Talpha1.

PMID- 29221123
TI  - VEGF-induced intracellular Ca2+ oscillations are down-regulated and do not
      stimulate angiogenesis in breast cancer-derived endothelial colony forming cells.
AB  - Endothelial colony forming cells (ECFCs) represent a population of truly
      endothelial precursors that promote the angiogenic switch in solid tumors, such
      as breast cancer (BC). The intracellular Ca2+ toolkit, which drives the pro
      angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that
      they are seemingly insensitive to this growth factor. This feature could underlie
      the relative failure of anti-VEGF therapies in cancer patients. Herein, we
      investigated whether and how VEGF uses Ca2+ signalling to control angiogenesis in
      BC-derived ECFCs (BC-ECFCs). Although VEGFR-2 was normally expressed, VEGF failed
      to induce proliferation and in vitro tubulogenesis in BC-ECFCs. Likewise, VEGF
      did not trigger robust Ca2+ oscillations in these cells. Similar to normal cells,
      VEGF-induced intracellular Ca2+ oscillations were triggered by inositol-1,4,5
      trisphosphate-dependent Ca2+ release from the endoplasmic reticulum (ER) and
      maintained by store-operated Ca2+ entry (SOCE). However, InsP3-dependent Ca2+
      release was significantly lower in BC-ECFCs due to the down-regulation of ER Ca2+
      levels, while there was no remarkable difference in the amplitude,
      pharmacological profile and molecular composition of SOCE. Thus, the attenuation
      of the pro-angiogenic Ca2+ response to VEGF was seemingly due to the reduction in
      ER Ca2+ concentration, which prevents VEGF from triggering robust intracellular
      Ca2+ oscillations. However, the pharmacological inhibition of SOCE prevented BC
      ECFC proliferation and in vitro tubulogenesis. These findings demonstrate for the
      first time that BC-ECFCs are insensitive to VEGF, which might explain at cellular
      and molecular levels the failure of anti-VEGF therapies in BC patients, and hint
      at SOCE as a novel molecular target for this disease.

PMID- 29221125
TI  - TCTN2: a novel tumor marker with oncogenic properties.
AB  - Tectonic family member 2 (TCTN2) encodes a transmembrane protein that belongs to
      the tectonic family, which is involved in ciliary functions. Previous studies
      have demonstrated the role of tectonics in regulating a variety of signaling
      pathways at the transition zone of cilia. However, the role of tectonics in
      cancer is still unclear. Here we identify that TCTN2 is overexpressed in
      colorectal, lung and ovary cancers. We show that different cancer cell lines
      express the protein that localizes at the plasma membrane, facing the
      intracellular milieu. TCTN2 over-expression in cancer cells resulted in an
      increased ability to form colonies in an anchorage independent way. On the other
      hand, downregulation of TCTN2 using targeted epigenetic editing in cancer cells
      significantly reduced colony formation, cell invasiveness, increased apoptosis
      and impaired assembly of primary cilia. Taken together, our results indicate that
      TCTN2 acts as an oncogene, making it an interesting cancer-associated protein and
      a potential candidate for therapeutic applications.

PMID- 29221126
TI  - The clinicopathological and prognostic significances of CDC73 expression in
      cancers: a bioinformatics analysis.
AB  - CDC73 interacts with human PAF1 complex, histone methyltransferase complex and
      RNA polymerase II for transcription elongation and 3' end processing. Its down
      regulated expression was immunohistochemically detected in gastric, colorectal,
      ovarian and head and neck cancers, and positively correlated with aggressive
      behaviors and unfavorable prognosis of malignancies. We performed a
      bioinformatics analysis by using Oncomine, TCGA and KM plotter databases. It was
      found that CDC73 mRNA was overexpressed in gastric, lung, breast and ovarian
      cancers, even stratified by histological subtypes (p<0.05). CDC73 mRNA expression
      was stronger in gastric intestinal- than diffuse-type carcinomas (p<0.05), and
      positively correlated with distant metastasis and TNM staging of lung cancer
      (p<0.05). CDC73 mRNA expression was positively related to both overall and
      progression-free survival rates of the patients with gastric cancer, even
      stratified by gender, lymph node involvement, or treatment (p<0.05), while versa
      for breast cancer (p<0.05). The prognostic significance of CDC73 mRNA was
      dependent on the datasets and pathological grouping in lung and ovarian cancers.
      These findings indicated the CDC73 mRNA overexpression was positively linked to
      carcinogenesis. It is cautious to employ CDC73 mRNA to evaluate the
      clinicopathological behaviors and prognosis of cancers.

PMID- 29221127
TI  - Long noncoding RNAs expression profile and functional networks in rheumatoid
      arthritis.
AB  - The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis
      (RA) recently have drawn much attention; however, the underlying mechanisms
      remain largely unknown. Herein, we aim to investigate the expression profile of
      lncRNAs in RA and identify promising targets for RA diagnosis and treatment.
      Microarray screening and real-time PCR of lncRNAs were performed by use of serum
      samples from 3 RA patients and 3 healthy controls. Significantly differentially
      expressed lncRNAs were verified in serum samples from 43 RA patients and 40
      healthy controls by real-time PCR. We found that there were 73 up-regulated and
      61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs
      in serum samples of RA patients. Validation in RA clinical samples indicated 5 of
      these lncRNAs were significantly up-regulated including RNA143598, RNA143596,
      HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed
      between these lncRNAs and the disease course, erythrocyte sedimentation rate
      (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti
      CCP) antibody. Additionally, 55 of the differentially expressed mRNAs were
      associated with 41 lncRNAs and were involved in signaling pathways of toll like
      receptors (TLRs), nuclear factor-kappa B (NF-kappaB), and cytokine, especially
      the IRF3/IRF7 mediated signaling transduction. Our study firstly shows the
      specific profile of lncRNAs in the serum of RA patients and potential signaling
      pathways involved in RA pathogenesis, which may provide novel targets for the
      diagnosis and treatment of patients with RA.

PMID- 29221128
TI  - MYCN-amplified stage 2/3 neuroblastoma: excellent survival in the era of anti-GD2
      immunotherapy.
AB  - High-risk neuroblastoma (HR-NB) includes MYCN-amplified stage 2/3, but reports
      covering anti-GD2 immunotherapy, which recently became standard for HR-NB, do not
      provide details on this subset. We now report on all 20 MYCN-amplified stage 2/3
      patients who received induction chemotherapy at our center during the era of
      consolidation with anti-GD2 antibody 3F8/ granulocyte-macrophage colony
      stimulating factor (GM-CSF) (2000-2015). Early in this period, consolidation
      included autologous stem-cell transplantation (ASCT). Event-free survival (EFS)
      and overall survival (OS) were estimated using Kaplan-Meier analyses. With
      induction, 19/20 (95%) patients achieved complete/very good partial remission
      (CR/VGPR) but one had progressive disease with early death. One responder did not
      receive consolidation and died of relapse. Five-year post-diagnosis EFS/OS rates
      for all 20 patients were 72%/84%. The 18 CR/VGPR patients who received
      consolidation had EFS/OS 81%/94% at five years from starting 3F8/GM-CSF: 4/4 ASCT
      patients remained relapse-free, while 11/14 non-ASCT patients remained relapse
      free and two of the three relapsed patients achieved 2nd CR (consolidated by
      retreatment with 3F8/GM-CSF) and remained in 2nd CR at 36+ and 95+ months post
      relapse. The 14 non-ASCT patients had EFS/OS 73.5%/93% at five years from
      starting 3F8/GM-CSF. This subset appears to have a good prognosis with
      contemporary multi-modality therapy, possibly even without ASCT.

PMID- 29221129
TI  - Long non-coding RNA polymorphisms in 6p21.1 are associated with atrophic
      gastritis risk and gastric cancer prognosis.
AB  - It has been suggested that the genetic variation in human chromosome 6p21.1 has
      potential importance for the susceptibility to gastric cancer (GC). The study
      aims to explore the relationship between the long non-coding RNA (lncRNA)
      polymorphisms in 6p21.1 and the risk of GC as well as atrophic gastritis (AG).
      Genotyping for eight single nucleotide polymorphisms (SNPs) was conducted using
      Sequenom MassARRAY platform in a total of 2507 northern Chinese subjects,
      including 749 GC cases, 878 AG cases and 880 controls. The results showed
      rs61516247 was associated with an increased AG risk in overall population (AA vs.
      GG: P = 0.046, OR = 1.46; A vs. G: P = 0.037, OR = 1.18). Four SNPs, rs61516247,
      rs1886753, rs7747696 and rs7749023 were associated with AG risk in some specific
      subgroups. Among them, rs1886753 had an interaction effect with H.pylori
      infection on AG risk (Pinteraction = 0.038, OR = 1.62). In prognosis analysis,
      two SNPs, rs80112640 (AG+GG vs. AA: P = 0.047, HR = 0.56; G vs. A: P = 0.039, HR
      = 0.57) and rs72855279 (P = 0.043, HR = 0.57) were found to improve the overall
      survival of GC patients. In conclusion, lncRNA SNPs in 6p21.1 are associated with
      AG risk and GC prognosis. Our study provides all-new research clues for screening
      lncRNA-based biomarkers in the cancer-related hotspot region 6p21.1 with the
      potential to predict risk and prognosis of GC along with its precursor.

PMID- 29221130
TI  - Development and cytotoxic response of two proliferative MDA-MB-231 and non
      proliferative SUM1315 three-dimensional cell culture models of triple-negative
      basal-like breast cancer cell lines.
AB  - Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers, are
      very aggressive and with poor prognosis. Targeted therapies have been developed
      extensively in preclinical and clinical studies to open the way for new treatment
      strategies. The present study has focused on developing 3D cell cultures from
      SUM1315 and MDA-MB-231, two triple-negative basal-like (TNBL) breast cancer cell
      lines, using the liquid overlay technique. Extracellular matrix concentration,
      cell density, proliferation, cell viability, topology and ultrastructure
      parameters were determined. The results showed that for both cell lines, the best
      conditioning regimen for compact and homogeneous spheroid formation was to use
      1000 cells per well and 2% Geltrex(r). This conditioning regimen highlighted two
      3D cell models: non-proliferative SUM1315 spheroids and proliferative MDA-MB-231
      spheroids. In both cell lines, the comparison of 2D vs 3D cell culture viability
      in the presence of increasing concentrations of chemotherapeutic agents i.e.
      cisplatin, docetaxel and epirubicin, showed that spheroids were clearly less
      sensitive than monolayer cell cultures. Moreover, a proliferative or non
      proliferative 3D cell line property would enable determination of cytotoxic
      and/or cytostatic drug activity. 3D cell culture could be an excellent tool in
      addition to the arsenal of techniques currently used in preclinical studies.

PMID- 29221131
TI  - Hoxa5 increases mitochondrial apoptosis by inhibiting Akt/mTORC1/S6K1 pathway in
      mice white adipocytes.
AB  - Homeobox A5(Hoxa5), a member of the Hox family, plays a important role in the
      regulation of proliferation and apoptosis in cancer cells. The dysregulation of
      the adipocyte apoptosis in vivo leads to obesity and metabolic disorders.
      However, the effects of Hoxa5 on adipocyte apoptosis are still unknown. In this
      study, palmitic acid (PA) significantly increased the mRNA level of Hoxa5 and
      triggered white adipocyte apoptosis in vivo and in vitro. Further analysis
      revealed that Hoxa5 enhanced the early and late apoptotic cells and fragmentation
      of genomic DNA in adipocytes from inguinal white adipose tissue (iWAT) of mice.
      Moreover, Hoxa5 aggravated white adipocyte apoptosis through mitochondrial
      pathway rather than endoplasmic reticulum stress (ERS)-induced or death receptor
      (DR)-mediated pathway. Our data also confirmed that Hoxa5 promoted mitochondrial
      apoptosis pathway by elevating the transcription activity of Bax and inhibiting
      the protein kinase B (Akt)/mammalian target of rapamycin complex 1 (mTORC1)
      signaling pathway. In summary, these findings revealed a novel mechanism that
      linked Hoxa5 to white adipocyte apoptosis, which provided some potential
      possibilities to prevent and treat obesity and some metabolic diseases.

PMID- 29221132
TI  - Neuroprotection of Botch in experimental intracerebral hemorrhage in rats.
AB  - Notch1 maturation participates in apoptosis and inflammation following
      intracerebral hemorrhage (ICH). It has been reported that Botch bound to and
      blocked Notch1 maturation. Here we estimated the role of Botch in ICH-induced
      secondary brain injury and underlying mechanisms. Experimental ICH model was
      induced by autologous arterial blood injection in Sprague-Dawley rats, and
      cultured primary rat cortical neurons were exposed to oxyhemoglobin to mimic ICH
      in vitro. Specific small interfering RNAs and expression plasmids encoding wild
      type Botch and Botch with Glu115Ala mutation were exploited. The protein levels
      of Botch and Notch1 transmembrane intracellular domain (Notch1-TMIC) were
      increased within brain tissue around hematoma. Botch overexpression led to an
      increase in unprocessed Notch1 full-length form accompanied by a significant
      decrease in Notch1-TMIC, while Botch knockdown resulted in an approximately 1.5
      fold increase in Notch1-TMIC. There were increased cell apoptosis, necrosis and
      neurobehavioral deficits after ICH, which was inhibited by Botch overexpression
      and enhanced by Botch knockdown. Double immunofluorescence showed a
      colocalization of Botch and Notch1 in the trans-Golgi. Overexpression of wild
      type Botch, but not Botch E115A mutant, led to an increase in the interaction
      between Botch and Notch1, reduced the formation and the nuclear localization of
      Notch1 intracellular domain, and attenuated cell apoptosis and inflammation. In
      conclusion, Botch exerts neuroprotection against neuronal damage via antagonizing
      the maturation of Notch1 in Glu115-denpendent manner. However, neuroprotection
      mediated by endogenous Botch is not enough to reverse ICH-induced secondary brain
      injury.

PMID- 29221133
TI  - Endogenous glutamine decrease is associated with pancreatic cancer progression.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of
      cancer-related death in the Western world. The mortality is very high, which
      emphasizes the need to identify biomarkers for early detection. As glutamine
      metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a
      useful tool for biomarker identification. Our aim was to identify a handy method
      to evaluate blood glutamine consumption in mouse models of PDAC. We quantified
      the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell
      supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and
      pancreatic control human cells. The increased glutamine uptake was paralleled by
      higher activity of most glutamine pathway-related enzymes supporting nucleotide
      and ATP production. Free glutamine blood levels were evaluated in orthotopic and
      spontaneous mouse models of PDAC and other pancreatic-related disorders by High
      Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a
      reduction of blood glutamine as much as the tumor progressed from pancreatic
      intraepithelial lesions to invasive PDAC, but was not related to chronic
      pancreatitis-associated inflammation or diabetes. In parallel the increased
      levels of branched-chain amino acids (BCAA) were observed. By contrast blood
      glutamine levels were stable in non-tumor bearing mice. These findings
      demonstrated that glutamine uptake is measurable both in vitro and in vivo. The
      higher in vitro avidity of PDAC cells corresponded to a lower blood glutamine
      level as soon as the tumor mass grew. The reduction in circulating glutamine
      represents a novel tool exploitable to implement other diagnostic or prognostic
      PDAC biomarkers.

PMID- 29221135
TI  - Silencing of BAG3 inhibits the epithelial-mesenchymal transition in human
      cervical cancer.
AB  - Bcl2-associated athanogene 3 (BAG3) has been reported to be involved in
      aggressive progression of many tumors. In the present study, we examined the
      expression of BAG3 in human cervical cancer (CC) tissues and investigated the
      role of BAG3 in SiHa and HeLa cell growth, migration, and invasion. Here, we
      found that most of CC tissues highly expressed the protein and mRNA of BAG3,
      while their expression was obviously lower in paired normal tissues (all
      p<0.001). BAG3 expression was associated with FIGO stage and metastasis (all
      p<0.05). In-vitro analysis demonstrated that BAG3 siRNAs inhibited SiHa and HeLa
      cell growth, invasion and migration. Mechanically, BAG3 siRNAs inhibited the
      expression of EMT-regulating markers, involving MMP2, Slug and N-cadherin, and
      increased the expression of E-cadherin. In a xenograft nude model, BAG3 siRNAs
      inhibited tumor growth and the expression of EMT biomarkers. In conclusion, BAG3
      is involved in the EMT process, including cell growth, invasion and migration in
      the development of CC. Thus, BAG3 target might be recommended as a novel
      therapeutic approach.

PMID- 29221134
TI  - A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in
      ovarian cancer cells.
AB  - Ovarian cancer is a complex disease marked by tumor heterogeneity, which
      contributes to difficulties in diagnosis and treatment. New molecular targets and
      better molecular profiles defining subsets of patients are needed. tRNA fragments
      (tRFs) offer a recently identified group of noncoding RNAs that are often as
      abundant as microRNAs in cancer cells. Initially their presence in deep
      sequencing data sets was attributed to the breakdown of mature tRNAs, however, it
      is now clear that they are actively generated and function in multiple regulatory
      events. One such tRF, a 5' fragment of tRNA-Glu-CTC (tRF5-Glu), is processed from
      the mature tRNA-Glu and is shown in this study to be expressed in ovarian cancer
      cells. We confirmed that tRF5-Glu binds directly to a site in the 3'UTR of the
      Breast Cancer Anti-Estrogen Resistance 3 (BCAR3) mRNA thereby down regulating its
      expression. BCAR3 has not previously been studied in ovarian cancer cells and our
      studies demonstrate that inhibiting BCAR3 expression suppresses ovarian cancer
      cell proliferation. Furthermore, mimics of tRF5-Glu were found to inhibit
      proliferation of ovarian cancer cells. In summary, BCAR3 and tRF5-Glu contribute
      to the complex tumor heterogeneity of ovarian cancer cells and may provide new
      targets for therapeutic intervention.

PMID- 29221136
TI  - KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis
      susceptibility.
AB  - To date, the genes associated with Psoriatic Arthritis (PsA) are principally
      involved in inflammation, immune response and epidermal differentiation, without
      any information about the relationship between disease and bone metabolism genes.
      Our work was focused on 5q31 locus, which contains several genetic variants
      significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426
      PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs
      of interest by Real Time PCR and direct sequencing. The results were subjected to
      biostatistic and bioinformatic analysis. The case-control study highlighted a
      significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis
      Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes
      significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD)
      study showed the presence of a specific block in high LD within 132,692,628
      132,737,638 bp of 5q31, giving additional evidence of specific association of the
      5q31 region in PsA patients. Moreover, KIF3A expression was assessed by
      immunohistochemistry assays which showed a marked and significant difference of
      KIF3A expression between pathological and normal tissues. Our analysis described
      KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear
      implication of bone metabolism genes in the disease etiopathogenesis.

PMID- 29221137
TI  - EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising
      antitumor activity in melanoma.
AB  - Melanoma is the most biologically aggressive skin cancer of well established
      constitutive and induced resistance to pharmacological treatment. Despite the
      recent progresses in immunotherapies, many advanced metastatic melanoma patients
      still face a significant mortality risk. The aggressive nature of this disease
      sustains an urgent need for more successful, effective drugs. HER-3 - one of the
      four member of the tyrosin kinase epidermal growth factor receptors (EGFRs)
      family- is frequently overexpressed in solid tumors, including melanoma.
      Moreover, up-regulation of HER-3 and its ligand NRGbeta-1 are associated with
      poor prognosis, thus suggesting this receptor as a suitable target for cancer
      therapy. Several monoclonal antibodies targeting HER-3 are currently available,
      but preliminary results from clinical testing of these agents reveal a modest
      efficacy. Thus, a substantial improvement over this immunotherapeutic approach
      could be offered by an anti-HER-3 based Antibody-Drug Conjugate (ADC). In the
      present paper, we describe the generation of an ADC obtained by coupling the HER
      3 targeting antibody EV20 linked to the plant toxin Saporin (Sap). In vitro, this
      ADC displays a powerful, specific and target-dependent cytotoxic activity which
      correlates with the degree of expression and internalization of HER-3 on tumor
      cells. Furthermore, in a murine melanoma model, EV20-Sap treatment leads to a
      significant reduction of the number of pulmonary metastasis.

PMID- 29221138
TI  - Gas signaling molecule hydrogen sulfide attenuates doxorubicin-induced dilated
      cardiomyopathy.
AB  - Increasing evidence has revealed that hydrogen sulfide (H2S) has beneficial
      effects in the treatment of various cardiovascular diseases. However, whether H2S
      can attenuate the development of dilated cardiomyopathy (DCM) remains unclear. In
      this study, we generated a rat model of DCM induced by doxorubicin and
      investigated the protective effects of H2S against DCM. Cardiac structure and
      function were analyzed by two-dimensional echocardiography. Oxidative stress was
      evaluated by measuring malondialdehyde, superoxide dismutase, glutathione
      peroxidase and reactive oxygen species. Cardiomyocyte apoptosis was assessed by
      flow cytometry following Annexin V/PI staining. Our results showed that exogenous
      administration of H2S could improve left ventricular structure and function in
      DCM rats. H2S was found to suppress doxorubicin-induced oxidative stress by
      activating the Nrf2 pathway and upregulating the expression of antioxidant
      proteins NQO1 and GCLM. Moreover, H2S was also found to inhibit doxorubicin
      induced cardiomyocyte apoptosis by activating the PI3K/Akt signaling pathway. In
      conclusion, our study demonstrates that H2S protects against doxorubicin-induced
      DCM via attenuation of oxidative stress and apoptosis.

PMID- 29221139
TI  - Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an
      innocent bystander or an autoimmunity mediator?
AB  - The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated
      autoimmune disorder affecting neuromuscular junction. Most MG patients have
      thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic
      epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases
      and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic
      MG thymuses, suggesting that EBV might contribute to intra-thymic B cell
      dysregulation in MG patients. Here, we investigated EBV involvement in thymoma
      associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14)
      thymomas. EBV DNA and EBV-encoded small nuclear RNA (EBER) 1 transcript were
      detected in 14/26 (53.8%) and 22/26 (84.6%) MG thymomas, and only in 3 of 14
      (21.4%) non-MG thymomas. Latent EBNA2 and late gp350/220 lytic transcripts were
      undetectable in all, but one, thymomas, and early lytic BZLF1 transcript was
      absent in all samples, suggesting that early infection events and EBV
      reactivation were very rare in thymomas. EBER1 and 2-positive cells were detected
      in MG, but not in non-MG, thymomas, as well as cells expressing EBV latency
      proteins (EBNA1, LMP1, LMP2A), that were mainly of B cell phenotype, indicating
      EBV association with MG rather than with thymoma. Toll-like receptor (TLR) 3
      transcriptional levels were higher in MG than non-MG thymomas and positively
      correlated with EBER1 levels, suggesting a role for EBERs in TLR3 activation. Our
      findings show that EBV is commonly present in thymoma-infiltrating B cells of
      myasthenic patients, indicating a contribution of EBV to B cell-mediated
      autoreactivity in MG associated with thymic tumor.

PMID- 29221140
TI  - Missing-in-metastasis B (MIM-B) combined with caveolin-1 promotes metastasis of
      hepatocellular carcinoma.
AB  - Background: Increasing amounts of evidence indicate that Missing in metastasis B
      (MIM-B) promotes cancer metastasis. Here, we sought to better understand the
      mechanism through which MIM-B promotes tumor metastasis in hepatocellular
      carcinoma (HCC). Methods: We performed confocal microscopy analysis to determine
      the distributions of MIM-B and caveolin-1 and conducted co-immunoprecipitation
      assays to detect the interactions between MIM-B and caveolin-1 in vitro. We
      performed transwell assays to analyze the invasive ability of HCC cells. Changes
      in the expression levels of key genes and some molecular makers were detected by
      immunohistochemistry and western blotting in HCC tissue samples. Results: We
      found that MIM-B co-localizes with caveolin-1 and demonstrated that MIM-B and
      caveolin-1 interact in vitro. Repressing MIM-B and caveolin-1 expression
      inhibited the epidermal growth factor receptor signaling pathway. We
      overexpressed MIM-B and caveolin-1 in Hep3B cells, which enhanced Hep3B cell
      invasiveness. Furthermore, MHCC97H cell invasiveness was significantly decreased
      in cells in which MIM-B and caveolin-1 expression was inhibited. Additionally, we
      found that MIM-B and caveolin-1 were expressed at higher levels in HCC tissues
      than in paired normal tissues. Moreover, HCC patients with MIM-B and caveolin-1
      up-regulation experienced significantly worse outcomes than controls (P < 0.001),
      and HCC patients with high MIM-B and caveolin-1 expression levels often developed
      pulmonary metastasis (P < 0.001). Conclusions: MIM-B combined with caveolin-1
      promotes metastasis of HCC, and elevated MIM-B and caveolin-1 expression levels
      are associated with a poor prognosis in HCC patients; therefore, MIM-B and
      caveolin-1 may represent novel targets for the diagnosis and treatment of HCC.

PMID- 29221141
TI  - Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung
      adenocarcinoma.
AB  - Exosomes and other extracellular vesicles (EVs) have been implicated as mediators
      of intercellular communication. Their release into the circulation has the
      potential to inform about tumor status. In-depth proteomic characterization of
      plasma-derived EVs has been limited by challenges in isolating EVs from protein
      abundant biological fluids. We implemented a novel single-step density gradient
      flotation workflow for efficient and rapid isolation of highly enriched
      circulating EVs from plasma. Mass-spectrometry analysis of plasma EVs from
      subjects with lung adenocarcinoma and matched controls resulted in the
      identification of 640 proteins. A total of 108 proteins exhibited significant
      (p<0.05) differential expression in vesicle preparations derived from lung
      adenocarcinoma case plasmas compared to controls, of which 43 were also
      identified in EVs from lung adenocarcinoma cell lines. Four top performing EV
      associated proteins that distinguished adenocarcinoma cases from controls, SRGN,
      TPM3, THBS1 and HUWE1, yielded a combined area under the receiver operating
      characteristic curve (AUC) of 0.90 (95% CI = 0.76-1). Our findings support the
      potential of EV derived proteins as a source of biomarkers that complement other
      approaches for tumor assessment.

PMID- 29221142
TI  - D-4F increases microRNA-124a and reduces neuroinflammation in diabetic stroke
      rats.
AB  - D-4F is an apolipoprotein-A1 mimetic peptide that promotes anti-inflammatory
      effects. MicroRNA-124 is the most abundant brain-specific microRNA and has anti
      inflammatory effects. In this study, we investigated the therapeutic efficacy and
      mechanisms of D-4F treatment of stroke in type one diabetes mellitus (T1DM) rats.
      Male Wistar rats were induced with T1DM, subjected to embolic middle cerebral
      artery occlusion and treated with PBS or D-4F (1 mg/kg i.p.) at 2, 24 and 48
      hours after stroke (n=8/group). A battery of function tests, brain blood barrier
      (BBB) integrity, white matter changes and microRNA expression were evaluated in
      vivo and in vitro. D-4F treatment in T1DM-stroke rats significantly improves
      functional outcome, decreases BBB leakage, increases tight junction protein
      expression, decreases white matter damage and inflammatory factor expression,
      while increasing anti-inflammatory M2 macrophage polarization in the ischemic
      brain. D-4F significantly increases microRNA-124a expression, and decreases
      matrix metalloproteinase-9, tumor necrosis factor-alpha and toll-like receptor-4
      gene expression in the ischemic brain, and in primary cortical neuronal and
      microglial cultures. Inhibition of microRNA-124 in cultured primary cortical
      neurons and microglia attenuates D-4F induced anti-inflammatory effects and M2
      macrophage polarization. D-4F treatment of T1DM-stroke increases microRNA-124
      expression, promotes anti-inflammatory effects and M2 macrophage polarization,
      which may contribute to D-4F-induced improvement in neurological function, and
      BBB and white matter integrity.

PMID- 29221143
TI  - Impact of human mesenchymal stromal cells on antifungal host response against
      Aspergillus fumigatus.
AB  - Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to
      hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus
      host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be
      beneficial in GvHD, there is, at the same time, major concern that MSCs increase
      the risk for infection. We therefore investigated the interplay of human MSCs
      with Aspergillus fumigatus and the impact of MSCs on different arms of the anti
      Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA
      levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro
      inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte
      Aspergillus conidia, but phagocytosis of conidia is not associated with an
      alteration of the cytokine production by MSCs. In addition, human MSCs do not
      affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do
      not negatively impact the oxidative burst activity of phagocytes. Our in vitro
      data indicate that administration of human MSCs is not associated with a negative
      impact on the host response against A. fumigatus and that the fungus does not
      stimulate MSCs to increase the release of those cytokines which play a central
      role in the pathophysiology of GvHD.

PMID- 29221144
TI  - UCP2 overexpression enhanced glycolysis via activation of PFKFB2 during skin cell
      transformation.
AB  - Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which
      is often upregulated in human cancers. However, how this anion transporter
      affects tumorigenesis is not well understood. Using the skin cell transformation
      JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase
      2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In
      conjunction, upregulation of PFKFB2 expression correlated with elevated fructose
      2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity,
      glucose uptake, and lactate production. Inhibiting PFKFB2 expression suppressed
      UCP2-mediated skin cell transformation, decreased cell proliferation, and
      enhanced mitochondrial respiration, while dampening aerobic glycolysis. The AKT
      signaling pathway was activated in the UCP2 overexpressed cells; furthermore, the
      activated AKT signaling contributed to the activation of PFKFB2. Whereas AKT
      inactivation blocked PFKFB2 activation, suggesting that AKT activation is an
      important step in PFKFB2 activation. Collectively, our data suggest that UCP2 is
      a critical regulator of cellular metabolism during cell transformation. Our data
      also demonstrate a potentially novel mechanism to understand UCP2's tumor
      promoting role, which is through the AKT-dependent activation of PFKFB2 and
      thereby, the metabolic shift to glycolysis (the Warburg effect).

PMID- 29221146
TI  - Swertiajaponin inhibits skin pigmentation by dual mechanisms to suppress
      tyrosinase.
AB  - Many skin-whitening compounds target tyrosinase because it catalyzes two rate
      limiting steps in melanin synthesis. Although many tyrosinase inhibitors are
      currently available for a skin-whitening purpose, undesirable adverse effects are
      also reported. Thus, numerous efforts have been made to develop safer tyrosinase
      inhibitors from natural products. In line with this, we tested fifty flavonoids,
      a group of naturally occurring antioxidants and metal chelators, and screened
      swertiajaponin as the strongest tyrosinase inhibitor in cell-free experiments.
      Swertiajaponin did not show cytotoxicity in B16F10, HaCat, and Hs27 cells and
      exhibited strong anti oxidative activity in experiments using the cell-free
      system and B16F10 cells. It markedly inhibited alphaMSH- or UVB-induced melanin
      accumulation in B16F10 cells and suppressed skin pigmentation in a human skin
      model. As underlying mechanisms, in silico and Lineweaver-Burk plot analyses
      exhibited that swertiajaponin may directly bind to and inhibit tyrosinase
      activity by forming multiple hydrogen bonds and hydrophobic interactions with the
      binding pocket of tyrosinase. In addition, western blotting results indicated
      that swertiajaponin inhibited oxidative stress-mediated MAPK/MITF signaling,
      leading to decrease in tyrosinase protein level. Together, swertiajaponin
      suppresses melanin accumulation by inhibiting both activity and protein
      expression levels of tyrosinase. Thus, it would be a novel additive for whitening
      cosmetics.

PMID- 29221145
TI  - Subependymal giant cell astrocytomas in Tuberous Sclerosis Complex have
      consistent TSC1/TSC2 biallelic inactivation, and no BRAF mutations.
AB  - Subependymal giant cell astrocytomas (SEGAs) are rare, low-grade glioneuronal
      brain tumors that occur almost exclusively in patients with tuberous sclerosis
      complex (TSC). Though histologically benign, SEGAs can lead to serious
      neurological complications, including hydrocephalus, intractable seizures and
      death. Previous studies in a limited number of SEGAs have provided evidence for a
      biallelic two-hit inactivation of either TSC1 or TSC2, resulting in constitutive
      activation of the mechanistic target of rapamycin complex 1 pathway. The
      activating BRAF V600E mutation is a common genetic alteration in low grade
      gliomas and glioneuronal tumors, and has been reported in SEGAs as well. In the
      present study, we assessed the prevalence of the BRAF V600E mutation in a large
      cohort of TSC related SEGAs (n=58 patients including 56 with clinical TSC) and
      found no evidence of either BRAF V600E or other mutations in BRAF. To confirm
      that these SEGAs fit the classic model of two hit TSC1 or TSC2 inactivation, we
      also performed massively parallel sequencing of these loci. Nineteen (19) of 34
      (56%) samples had mutations in TSC2, 10 (29%) had mutations in TSC1, while 5
      (15%) had no mutation identified in TSC1/TSC2. The majority of these samples had
      loss of heterozygosity in the same gene in which the mutation was identified.
      These results significantly extend previous studies, and in agreement with the
      Knudson two hit mechanism indicate that biallelic alterations in TSC2 and less
      commonly, TSC1 are consistently seen in SEGAs.

PMID- 29221147
TI  - Long noncoding RNA LINC00673 epigenetically suppresses KLF4 by interacting with
      EZH2 and DNMT1 in gastric cancer.
AB  - Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding
      ability, have recently been reported to play vital roles in gastric cancer (GC)
      development and progression. However, the biological role of long non-coding RNA
      LINC00673 in GC is not fully known. In the study, we found that LINC00673
      expression was dramatically higher in gastric cancer tissues compared with
      adjacent normal tissues, and positively associated with lymph node metastasis,
      distant metastasis and TNM stage in patients. Higher LINC00673 expression
      predicted poor disease-free survival (DFS) and overall survival (OS) in GC
      patients. By univariate and multivariate Cox analysis, the results confirmed that
      higher LINC00673 expression was an independent risk factor of prognosis in
      patients. Knockdown of endogenous LINC00673 significantly inhibited cell
      proliferation, colony formation number, cell migration and invasion in GC.
      Furthermore, knockdown of endogenous LINC00673 reduced the expression levels of
      PCNA, CyclinD1 and CDK2 in GC cells. RNA immunoprecipitation (RIP) and chromatin
      immunoprecipitation (ChIP) proved that LINC00673 suppressed KLF4 expression by
      interacting with EZH2 and DNMT1 in GC cells. Moreover, we confirmed that
      LINC00673 promoted cell proliferation and invasion by partly repressing KLF4
      expression in GC. Taken together, these results indicated that LINC00673 may be a
      prognostic biomarker and therapeutic target for GC patients.

PMID- 29221148
TI  - Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low
      dose hydroquinone.
AB  - Previous studies have shown that long noncoding RNAs (lncRNAs) were related to
      human carcinogenesis and might be designated as diagnosis and prognosis
      biomarkers. Hydroquinone (HQ), as one of the metabolites of benzene, was closely
      relevant to occupational benzene poisoning and occupational leukemia. Using high
      throughput sequencing technology, we investigated differences in lncRNA and mRNA
      expression profiles between experimental group (HQ 20 MUmol/L) and control group
      (PBS). Compared to control group, a total of 65 lncRNAs and 186 mRNAs were
      previously identified to be aberrantly expressed more than two fold change in
      experimental group. To validate the sequencing results, we selected 10 lncRNAs
      and 10 mRNAs for quantitative real-time PCR (qRT-PCR). Through GO annotation and
      KEGG pathway analysis, we obtained 3 mainly signaling pathways, including P53
      signaling pathway, which plays an important role in tumorigenesis and
      progression. After that, 25 lncRNAs and 32 mRNAs formed the lncRNA-mRNA co
      expression network were implemented to play biological functions of the
      dysregulated lncRNAs transcripts by regulating gene expression. The lncRNAs
      target genes prediction provided a new idea for the study of lncRNAs. Finally, we
      have another important discovery, which is screened out 11 new lncRNAs without
      annotated. All these results uncovered that lncRNA and mRNA expression profiles
      in TK6 cells exposed to low dose HQ were different from control group, helping to
      further study the toxicity mechanisms of HQ and providing a new direction for the
      therapy of leukemia.

PMID- 29221149
TI  - Prediction on the risk population of idiosyncratic adverse reactions based on
      molecular docking with mutant proteins.
AB  - Idiosyncratic adverse drug reactions are drug reactions that occur rarely and
      unpredictably among the population. These reactions often occur after a drug is
      marketed, which means that they are strongly related to the genotype of the
      population. The prediction of such adverse reactions is a major challenge because
      of the lack of appropriate test models during the drug development process. In
      this study, we chose withdrawn drugs because the reasons why they were withdrawn
      and from which countries or regions is easily obtained. We selected Dilevalol and
      its chiral drug (Labetalol) as the investigatory drugs, as they have been
      withdrawn from a European market (Britain) because of serious hepatotoxicity.
      First, we searched for and obtained the Dilevalol-induced- liver-injury related
      protein, multidrug resistance protein 1 (MDR1), from the Comparative
      Toxicogenomics Database (CTD). Then, we searched and extracted 477 non-synonymous
      single nucleotide polymorphisms (nsSNP) on MDR1 in the dbSNP database. Second, we
      used the VarMod tool to predict the functional changes of MDR1 induced by these
      nsSNPs, from which we extracted the nsSNPs that significantly change the
      functions of this protein. Third, we built the three-dimensional structures of
      those variant proteins and used AutoDock to perform a docking study, choosing the
      best model to determine the sites of nsSNPs. Finally, we used the data from the
      1000 Genomes Project to verify the dominant population distribution of the risk
      SNP. We applied the same strategy to the post-marketing drug-induced liver injury
      drugs to further test the feasibility of our method.

PMID- 29221150
TI  - Comparison of gross tumor volume of primary oesophageal cancer based on contrast
      enhanced three-dimensional, four-dimensional, and cone beam computed tomography.
AB  - Background: To explore motion information included in 3DCT, 4DCT and CBCT by
      comparing volumetric and positional differences of GTV. Results: Independent of
      tumor location, significant differences were observed among volumes [IGTV10 >
      (IGTVCBCT or IGTVMIP) > (GTV3D or GTV4D50)]. The underestimations or
      overestimations between IGTV10 and IGTVCBCT were larger than those between IGTV10
      and IGTVMIP (p < 0.001-0.011; p < 0.001-0.023). For upper oesophageal tumors,
      GTV4D50/IGTVCBCT negatively correlated with motion vector (r = -0.756, p =
      0.011). In AP direction, the centroid coordinates of IGTVCBCT differed from
      GTV3D, GTV4D50, IGTVMIP and IGTV10 (p = 0.006, 0.013, 0.038, and 0.010). For
      middle oesophageal tumors, IGTV10/IGTVCBCT positively correlated with motion
      vector (r = 0.695, p = 0.006). The centroid coordinates of IGTVCBCT differed from
      those of IGTV10 (p = 0.046) in AP direction. For distal oesophageal tumors, the
      centroid coordinates of IGTVCBCT showed significant differences to those of
      IGTVMIP (p = 0.042) in LR direction. For both middle and distal tumors, the
      degrees of associations of IGTV10 outside IGTVCBCT significantly correlated with
      the motion vector (r = 0.540, p = 0.046; r = 0.678, p = 0.031). Materials and
      Methods: Thirty-four oesophageal cancer patients underwent 3DCT, 4DCT and CBCT.
      GTV3D, GTV4D50, internal GTVMIP (IGTVMIP) and IGTVCBCT were delineated on 3DCT,
      4DCT50, 4DCTMIP and CBCT. GTVs from 10 respiratory phases were combined to
      produce GTV10. Differences in volume, position for different targets, correlation
      between volume ratio and motion vector were evaluated. The motion vector was the
      spatial moving of the target centroid position. Conclusions: IGTVCBCT encompasses
      more motion information than GTV3D and GTV4D50 for upper oesophageal tumors, but
      slightly less than IGTV10 for middle and distal oesophageal tumors. IGTVCBCT
      incorporated similar motion information to IGTVMIP. However, motion information
      encompassed in CBCT and MIP cannot replace each other.

PMID- 29221151
TI  - Collagen I promotes hepatocellular carcinoma cell proliferation by regulating
      integrin beta1/FAK signaling pathway in nonalcoholic fatty liver.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become a major risk factor for
      hepatocellular carcinoma (HCC) worldwide. However, the underlying mechanism
      remains insufficiently elucidated. The expression of Collagen I, an important
      component of extracellular matrix (ECM), was increased during the progression
      from simple steatosis to NASH. The purpose of this study was to investigate the
      role of Collagen I in NAFLD-related HCC. To study this, the decellularized liver
      matrix, which preserves the pathological changes of ECM, was prepared from the
      human fatty liver (FLM) and human normal liver (NLM). HepG2 cells cultured in FLM
      had a higher proliferation rate than those in NLM. SMMC-7721 and HepG2 cells
      cultured on Collagen I-coated plates grew faster than those on either Collagen IV
      or fibronectin-coated plates. This effect was dose-dependent and associated with
      elevated integrin beta1 expression and activation of downstream phospho-FAK.
      Knocking down the expression of integrin beta1 significantly decreased the
      proliferation of HCC cells. Additionally, an orthotopic tumor model was
      established in NAFLD mice at different stages. The over-expressed Collagen I in
      the mice liver increased the expression of integrin beta1 and downstream phospho
      FAK, resulting in the proliferation of HCC cells. This proliferation could be
      inhibited by blocking the integrin beta1/FAK pathway. In summary, our study
      demonstrated that Collagen I promoted HCC cell proliferation by regulating the
      integrin beta1/FAK pathway. Decellularized liver matrix can be used as a platform
      to three-dimensionally culture HCC cells and reproduce the impact of changed ECM
      on the progression of NAFLD-related HCC.

PMID- 29221152
TI  - Distal embolization versus combined embolization techniques for blunt splenic
      injuries: comparison of the efficacy and complications.
AB  - Comparable failure rates of distal or proximal transcatheter arterial
      embolization (TAE) techniques for blunt splenic injuries have been reported. This
      study is to investigate the efficacy and complication of combining both TAE
      techniques. We included 26 patients of blunt splenic injuries for TAE therapy and
      randomized them into distal TAE and combined TAE groups. A prospective study was
      performed to compare their demographics, clinical parameters, hemograms, post-TAE
      splenic infarct volumes, splenic abscess and pancreatitis between the two groups.
      Of 26 patients, 17 received distal TAE, 9 received combined TAE. Their basic
      demographics, clinical parameters and hemograms did not differ. Mean systolic
      blood pressure of all patients was significantly elevated after TAE at 24 hours
      later. Three patients of distal TAE group had residual pseudoaneurysms in follow
      up. They were considered failures in distal TAE group as opposed to all successes
      in combined TAE group. The risk difference of failure of distal TAE was 17.6%.
      None developed post-TAE splenic abscess, massive splenic infarct or pancreatitis.
      The mean splenic infarct volume of distal TAE (10.9%) versus combined TAE groups
      (6.6%) was not significant (p = 0.481). Combined TAE is effective and safe to
      decrease the failure rates of non-operative management for blunt splenic
      injuries.

PMID- 29221153
TI  - [68Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model -
      comparison with [18F]FDG PET/CT, MRI and ex vivo receptor expression.
AB  - Purpose: The aim was to characterize the properties of [68Ga]Pentixafor as tracer
      for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and
      to investigate its correlation with [18F]FDG PET/CT, magnetic resonance imaging
      (MRI) and ex vivo analyses. Methods: Static [68Ga]Pentixafor and [18F]FDG PET as
      well as morphological/ diffusion weighted MRI and 1H MR spectroscopy was
      performed. Imaging data were correlated with ex vivo biodistribution and CXCR4
      expression in PC-3 tumors (immunohistochemistry (IHC), mRNA analysis). Flow
      cytometry was performed for evaluation of localization of CXCR4 receptors (in
      vitro PC-3 cell experiments). Results: Tumor uptake of [68Ga]Pentixafor was
      significantly lower compared to [18F]FDG. Ex vivo CXCR4 mRNA expression of tumors
      was shown by PCR. Only faint tumor CXCR4 expression was shown by IHC (immuno
      reactive score of 3). Accordingly, flow cytometry of PC-3 cells revealed only a
      faint signal, cell membrane permeabilisation showed a slight signal increase.
      There was no significant correlation of [68Ga]Pentixafor tumor uptake and ex vivo
      receptor expression. Spectroscopy showed typical spectra of prostate cancer.
      Conclusion: PC-3 tumor uptake of [68Ga]Pentixafor was existent but lower compared
      to [18F]FDG. No significant correlation of ex vivo tumor CXCR4 receptor
      expression and [68Ga]Pentixafor tumor uptake was shown. CXCR4 receptor expression
      on the surface of PC-3 cells was existent but rather low possibly explaining the
      limited [68Ga]Pentixafor tumor uptake; receptor localization in the interior of
      PC-3 cells is presumable as shown by cell membrane permeabilisation. Further
      studies are necessary to define the role of [68Ga]Pentixafor in prostate cancer
      imaging.

PMID- 29221154
TI  - Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype
      in bladder cancer.
AB  - High-grade Bladder Cancer (BLCA) represents the most aggressive and treatment
      resistant cancer that renders the patients with poor survival. However, only a
      few biomarkers have been identified for the detection and treatment of BLCA.
      Recent studies show that ganglioside GD2 can be used as cancer biomarker and/or
      therapeutic target for various cancers. Despite its potential relevance in cancer
      diagnosis and therapeutics, the role of GD2 is unknown in BLCA. Here, we report
      for the first time that high-grade BLCA tissues and cell lines have higher
      expression of GD2 compared to low-grade by high-resolution Mass Spectrometry. The
      muscle invasive UMUC3 cell line showed high GD2, mesenchymal phenotype, and cell
      proliferation. Besides, we have shown the cancer stem cells (CSC) property
      (CD44hiCD24lo) of GD2+ UMUC3 and J82 cells. Also, the evaluation of lipid
      metabolism in GD2+ BLCA cell lines revealed higher levels of Phosphatidylinositol
      (PI), Phosphatidic acid (PA), Cardiolipin (CL) and lower levels of
      Phosphatidylserine (PS), plasmenyl-phosphatidylethanolamines (pPE), plasmenyl
      phosphocholines (pPC), sphingomyelins (SM), triglycerides (TGs) and N
      Acetylneuraminic acid. These findings are significantly correlated with the
      tissues of BLCA patients. Based on this evidence, we propose that GD2 may be used
      as an effective diagnostic and therapeutic target for aggressive BLCA.

PMID- 29221155
TI  - CD109 released from human bone marrow mesenchymal stem cells attenuates TGF-beta
      induced epithelial to mesenchymal transition and stemness of squamous cell
      carcinoma.
AB  - Although there is increasing evidence that human bone marrow mesenchymal stem
      cells (hBM-MSCs) play an important role in cancer progression, the underlying
      mechanisms are poorly understood. Transforming growth factor beta (TGF-beta) is
      an important pro-metastatic cytokine. We have previously shown that CD109, a
      glycosylphosphatidylinositol-anchored protein, is a TGF-beta co-receptor and a
      strong inhibitor of TGF-beta signalling. Moreover, CD109 can be released from the
      cell surface. In the current study, we examined whether hBM-MSCs regulate the
      malignant properties of squamous cell carcinoma cells, and whether CD109 plays a
      role in mediating the effect of hBM-MSCs on cancer cells. Here we show that hBM
      MSC-conditioned medium decreases proliferation and induces apoptosis in human
      squamous carcinoma cell lines, A431 and FaDu. Importantly, hBM-MSC-conditioned
      medium markedly suppresses markers of epithelial-to-mesenchymal transition and
      stemness, and concomitantly decreases cell migration, invasion, and spheroid
      formation in A431 and FaDu cells. In addition, knockdown of CD109 in hBM-MSCs
      abrogates the anti-malignant activity of hBM-MSC-conditioned medium on A431 and
      FaDu cells. Furthermore, overexpression of CD109 in A431 cells decreases their
      malignant traits. Together, our findings suggest that hBM-MSCs inhibit the
      malignant traits of squamous cell carcinoma cells by a paracrine effect via
      released factors and that CD109 released from hBM-MSCs, at least partially,
      mediates these effects.

PMID- 29221156
TI  - The protective role of sphingosine-1-phosphate against the action of the vascular
      disrupting agent combretastatin A-4 3-O-phosphate.
AB  - Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin
      A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The
      signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier
      integrity by promoting assembly of VE-cadherin/beta-catenin complexes. We tested
      the hypothesis that tumour pre-treatment with S1P would render tumours less
      susceptible to CA4P. S1P (1MUM) pretreatment attenuated an increase in
      endothelial cell (HUVEC) monolayer permeability induced by 10MUM CA4P.
      Intravenously administered S1P (8mg/kg/hr for 20 minutes then 2mg/kg/hr for 40
      minutes), reduced CA4P-induced (30mg/kg) blood flow shut-down in fibrosarcoma
      tumours in SCID mice (n>=7 per group), as measured by tumour retention of an
      intravenously administered fluorescent lectin. A trend towards in vivo protection
      was also found using laser Doppler flowmetry. Immunohistochemical staining of
      tumours ex vivo revealed disrupted patterns of VE-cadherin in vasculature of mice
      treated with CA4P, which were decreased by pretreatment with S1P. S1P treatment
      also stabilized N-cadherin junctions between endothelial cells and smooth muscle
      cells in culture, and stabilized tubulin filaments in HUVEC monolayers. We
      conclude that the rapid shutdown of tumour microvasculature by CA4P is due in
      part to disruption of adherens junctions and that S1P has a protective effect on
      both adherens junctions and the endothelial cell cytoskeleton.

PMID- 29221157
TI  - High PTPN13 expression in high grade serous ovarian carcinoma is associated with
      a better patient outcome.
AB  - Background: Chromosome 4q loss of heterozygosity (LOH) is frequently observed in
      high-grade serous ovarian carcinoma (HGSOC). However, this LOH has not been
      clearly associated with the inactivation of any tumor suppressor gene(s). As the
      tumor suppressor gene PTPN13 is located on chromosome 4q21, we investigated its
      expression in HGSOC. Methods: PTPN13 protein expression was investigated by
      immunohistochemistry (IHC) in normal ovary epithelium and in 30 HGSOC samples,
      whereas PTPN13 mRNA expression was quantified by RT-PCR in another independent
      cohort of 28 HGSOC samples. Patients in both cohorts were followed for more than
      8.5 years. Results: PTPN13 protein expression was lower in one third of HGSOC
      samples compared with normal ovary epithelium. In both cohorts, high PTPN13
      expression level (mRNA or protein) in the tumor was associated with favorable
      outcome and significantly longer survival (HR=0.27; p=0.0087 and HR=0.42; p=0.03,
      respectively). Conclusion: This study demonstrates, for the first time, that high
      PTPN13 expression level is a prognostic indicator of favorable outcome in
      patients with HGSOC. This finding, in conjunction with our previous mechanistic
      studies, suggests that PTPN13 loss, possibly by 4q LOH, enhances HGSOC
      aggressiveness and highlight the interest of studying PTPN13 signaling in HGSOC
      to identify new potential therapeutic targets.

PMID- 29221158
TI  - Epigenetic silencing of miR-296 and miR-512 ensures hTERT dependent apoptosis
      protection and telomere maintenance in basal-type breast cancer cells.
AB  - The catalytic subunit of the telomerase complex, hTERT, ensures unlimited
      proliferative potential of cancer cells by maintaining telomere function and
      protecting from apoptosis. Using a miRNA screening approach we identified miR-296
      5p and miR-512-5p as miRNAs that target hTERT in breast cancer cells. Ectopic miR
      296-5p and miR-512-5p reduce telomerase activity, drive telomere shortening and
      cause proliferation defects by enhancing senescence and apoptosis in breast
      cancer cells. In line with the relevance of hTERT expression for human cancer we
      found that miR-296-5p and miR-512-5p expression is reduced in human breast
      cancer. Accordingly, high expression of miR-296-5p and miR-512-5p target genes
      including hTERT is linked with significantly reduced distant metastasis free
      survival and relapse free survival of basal type breast cancer patients. This
      suggests relevance of the identified miRNAs in basal type breast cancer.
      Epigenetic silencing of miR-296 and miR-512 encoding genes is responsible for low
      levels of miR-296-5p and miR-512-5p expression in basal type breast cancer cells.
      Disrupting gene silencing results in a dramatic upregulation of miR-296-5p and
      miR-512-5p levels leading to reduced hTERT expression and increased sensitivity
      to the induction of apoptosis. Altogether, our data suggest that epigenetic
      regulatory circuits in basal type breast cancer may contribute to high hTERT
      levels by silencing miR-296-5p and miR-512-5p expression, thereby contributing to
      the aggressiveness of basal type breast cancer.

PMID- 29221159
TI  - Melatonin suppresses fibrotic responses induced by cigarette smoke via
      downregulation of TGF-beta1.
AB  - Cigarette smoke (CS) is the most important risk factor in the development of
      chronic obstructive pulmonary disease (COPD). Pulmonary fibrosis is an
      irreversible response and important feature of COPD. In this study, we
      investigated the effects of melatonin on fibrotic response in development of COPD
      using a CS and lipopolysaccharide (LPS) induced COPD model and cigarette smoke
      condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid cell line.
      Mice were exposed to CS for 1 h per day (8 cigarettes per day) from day 1 to day
      7 and were treated intranasally with LPS on day 4. Melatonin (10 or 20 mg/kg) was
      injected intraperitoneally 1 h before CS exposure. Melatonin decreased the
      inflammatory cell counts in bronchoalveolar lavage fluid (BALF), with a reduction
      in transforming growth factor (TGF)-beta1. Melatonin inhibited the expression of
      TGF-beta1, collagen I and SMAD3 phosphorylation in lung tissue exposed to CS and
      LPS. In CSC-stimulated H292 cells, melatonin suppressed the elevated expression
      of fibrotic mediators induced by CSC treatment. Melatonin reduced the expression
      of TGF-beta1, collagen I, SMAD3 and p38 phosphorylation in CSC-stimulated H292
      cells. In addition, cotreatment with melatonin and TGF-beta1 inhibitors
      significantly limited fibrotic mediators, with greater reductions in the
      expression of TGF-beta1, collagen I, SMAD3 and p38 phosphorylation than those of
      H292 cells treated with TGF-beta1 inhibitor alone. Taken together, melatonin
      effectively inhibited fibrotic responses induced by CS and LPS exposure, which
      was related to the downregulation of TGF-beta1. Therefore, our results suggest
      that melatonin may suppress the pulmonary fibrotic response induced by CS.

PMID- 29221160
TI  - Circular RNA profile indicates circular RNA VRK1 is negatively related with
      breast cancer stem cells.
AB  - Circular RNAs (circRNAs), a novel type of noncoding RNAs (ncRNAs), have been
      shown to be implicated in biological processes including cancer as gene
      expression regulators. However, the roles of circRNAs in cancer stem cells (CSCs)
      have been unexplored. In the present study, we screened the circRNA profile in
      breast cancer stem cells (BCSCs) using RNA-Sequencing. Here, 27 circRNAs were
      found to be aberrantly expressed. Of these, 19 circRNAs were downregulated and 8
      were upregulated and some of these circRNAs were validated by Q-PCR. Furthermore,
      we constructed the circRNA/miRNA network by bioinformatics approaches and
      hypothesized that circRNAs might be involved in stemness of BCSCs via serving as
      miRNA sponges. Importantly, we found that circular RNA VRK1 (circVRK1) could
      suppress BCSC's expansion and self-renewal capacity. Collectively, the present
      work provides the first reported evidence of the circRNA profile and
      circRNA/miRNA interplay in BCSCs. In addition, these findings lay foundation to
      explore the functions of circRNAs in CSCs and indicate that circVRK1 might be a
      promising target for BCSCs.

PMID- 29221161
TI  - Piriform cortical glutamatergic and GABAergic neurons express coordinated
      plasticity for whisker-induced odor recall.
AB  - Neural plasticity occurs in learning and memory. Coordinated plasticity at
      glutamatergic and GABAergic neurons during memory formation remains elusive,
      which we investigate in a mouse model of associative learning by cellular imaging
      and electrophysiology. Paired odor and whisker stimulations lead to whisker
      induced olfaction response. In mice that express this cross-modal memory, the
      neurons in the piriform cortex are recruited to encode newly acquired whisker
      signal alongside innate odor signal, and their response patterns to these
      associated signals are different. There are emerged synaptic innervations from
      barrel cortical neurons to piriform cortical neurons from these mice. These
      results indicate the recruitment of associative memory cells in the piriform
      cortex after associative memory. In terms of the structural and functional
      plasticity at these associative memory cells in the piriform cortex,
      glutamatergic neurons and synapses are upregulated, GABAergic neurons and
      synapses are downregulated as well as their mutual innervations are refined in
      the coordinated manner. Therefore, the associated activations of sensory cortices
      triggered by their input signals induce the formation of their mutual synapse
      innervations, the recruitment of associative memory cells and the coordinated
      plasticity between the GABAergic and glutamatergic neurons, which work for
      associative memory cells to encode cross-modal associated signals in their
      integration, associative storage and distinguishable retrieval.

PMID- 29221162
TI  - Caveolin-1-mediated STAT3 activation determines electrotaxis of human lung cancer
      cells.
AB  - Migration of cancer cells leads to the invasion of distant organs by primary
      tumors. Further, endogenous electric fields (EFs) in the tumor microenvironment
      direct the migration of lung cancer cells by a process referred to as
      electrotaxis - although the precise mechanism remains unclear. Caveolin-1 (Cav-1)
      is a multifunctional scaffolding protein that is associated with directional cell
      migration and lung cancer invasion; however, its precise role in lung cancer
      electrotaxis is unknown. In the present study, we first detected outward electric
      currents on the tumor body surface in lung cancer xenografts using a highly
      sensitive vibrating probe. Next, we found that highly-metastatic H1650-M3 cells
      migrated directionally to the cathode. In addition, reversal of the EF polarity
      reversed the direction of migration. Mechanistically, EFs activated Cav-1 and the
      downstream signaling molecule STAT3. RNA interference of Cav-1 reduced
      directional cell migration, which was accompanied by dampened STAT3 activation.
      Furthermore, pharmacological inhibition of STAT3 significantly reduced the
      electrotactic response, while rescue of STAT3 activation in Cav-1 knock-down
      cells restored electrotaxis. Taken together, these results suggest that
      endogenous EFs in the tumor micro-environment might play an important role in
      lung cancer metastasis by guiding cell migration through a Cav-1/STAT3-mediated
      signaling pathway.

PMID- 29221163
TI  - Association of miR-21, miR-126 and miR-605 gene polymorphisms with ischemic
      stroke risk.
AB  - We investigated whether three common microRNA polymorphisms (miR-21T>C
      [rs1292037], miR-126G>A [rs4636297] and miR-605T>C [rs2043556]) were associated
      with ischemic stroke (IS) risk in a Chinese population. The study population
      comprised 592 ischemic stroke patients and 456 normal controls. The polymorphisms
      were measured using Snapshot SNP genotyping assays and confirmed by sequencing.
      Relative expressions of miR-21, miR-126 and miR-605 were measured by quantitative
      real-time PCR. We found that miR-126 gene rs4636297 polymorphism was associated
      with decreased ischemic stroke risk (GA vs. GG: AOR=0.64, adjust P=0.025; AA vs.
      GG: AOR=0.32, adjust P=0.007; dominant model: AOR=0.58, adjust P=0.004). MiR-21
      gene rs1292037 and miR-605 gene rs2043556 polymorphisms were not associated with
      ischemic stroke risk. In addition, compared with normal controls, serum miR-126
      level was significantly decreased in ischemic stroke patients, while the miR-21
      level was significantly increased. Importantly, patients carrying rs4636297 GA/AA
      genotypes had higher serum miR-126 level (P<0.05). MiR-126 gene rs4636297
      polymorphism and serum miR-126/-21 levels are associated with ischemic stroke
      risk. Our data indicates that miR-126 and miR-21 play roles in the development of
      ischemic stroke.

PMID- 29221164
TI  - Inhibition of X-linked inhibitor of apoptosis protein suppresses tumorigenesis
      and enhances chemosensitivity in anaplastic thyroid carcinoma.
AB  - Anaplastic thyroid carcinoma (ATC) is one of the most lethal carcinoma with a
      poor prognosis; however, molecular mechanisms underlying the aggressiveness of
      ATC remain unclear. Our goal was to examine the expression of X-linked inhibitor
      of apoptosis protein (XIAP) in ATC, as well as its role in ATC tumorigenesis.
      This is a retrospective study of ATC patients from the Second Affiliated Hospital
      of Harbin Medical University during June 2003 to October 2013. The expression of
      XIAP in tumor specimens of ATC patients was examined by immunohistochemical
      staining. The roles of XIAP in proliferation, migration, invasion, and
      chemoresistance were investigated by shRNA mediated-knockdown of XIAP in human
      ATC cell lines. The effect of XIAP on tumorigenesis was evaluated using a
      xenograft tumor model with nude mice. XIAP expression was significantly higher in
      the invasive area of ATC samples, whereas XIAP expression was negative in either
      normal thyroid follicular epithelial cells or the differentiated papillary
      thyroid carcinoma. XIAP-depleted ATC cells showed a remarkable decrease in the
      proliferation, migration, and invasion compared with the scramble group.
      Knockdown of XIAP expression significantly enhanced the chemosensitivity of WRO
      and SW1736 cells to docetaxel or taxane. Moreover, knockdown of XIAP
      significantly suppressed ATC tumorigenesis in vivo. XIAP is highly expressed in
      ATC cells and tumors. XIAP play important roles in tumor behaviors and
      chemosensitivity of ATC cells. XIAP may function in ATC aggressiveness and may
      serve as a potential therapeutic target for ATC treatment.

PMID- 29221165
TI  - Angiogenesis in adenosquamous cancer of pancreas.
AB  - Adenosquamous carcinoma of the pancreas (ASCP) is an uncommon variant of exocrine
      pancreatic malignancies, characterized by a histological admixture of adenomatous
      and squamous cell elements. This cancer is characterized by a poorly
      differentiated histology and a poorer clinical outcome compared to pancreatic
      ductal adenocarcinoma (PDAC). Unlike PDAC, that is characterized by a low
      microvascular density (MVD) and collapsed vasculature, no data are available
      about angiogenesis in ASPC. Immunohistochemical evaluation of MVD and trypatse
      positive mast cells (MCs) were performed on a single case of ASCP compared to
      PDAC. Moreover, the levels of angiopoietin-1 and -2 (Ang-1, Ang-2), receptor
      tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2
      (Tie-2), vascular endothelial growth factor A (VEGFA), hypoxia-inducible factor 1
      alpha (HIF1A), miR-21-5p, miR-181a-5p, miR-122-5p, and miR-27a-3p were evaluated
      by real-time PCR. Higher number of tryptase-positive MCs and MVD are observed in
      the ASCP case compared to PDAC one. Lower levels of miR-122-5p and higher
      expression of VEGFA, HIF1A and Ang-2 genes were observed in ASCP. Furthermore,
      lower Ang-1 and Tie-2 transcript levels and higher increases of miR-21-5p, miR27a
      3p and miR-181a-5p levels were found in the rarest form of pancreatic carcinoma.
      Our data demonstrate an important angiogenic activity in ASCP with a putative
      role of miR-21-5p, miR-181a-5p, miR-122-5p and miR-27a-3p in the regulation of
      this process.

PMID- 29221166
TI  - High salt induced hypertension leads to cognitive defect.
AB  - Although increasing evidences suggest a relationship between hypertension and
      brain function for years, it is still unclear whether hypertension constitutes a
      risk factor for cognitive decline and its underlying mechanism. In the present
      study, an experimental animal model of hypertension simply by feeding rats with
      high salt diet was employed. We found that long-term high salt intake caused a
      marked increase of systolic blood pressure linked to a declined regional cerebral
      blood flow. Fear conditioning and morris water maze behavioral test revealed that
      high salt diet induced hippocampal dependent spatial reference memory deficits,
      while a decreased synaptogenesis without neuronal loss in hippocampus was
      observed in high salt treated rats. Furthermore, we found that high salt induced
      a decrease of intracellular calcium, which inactivated CaMK II and resulted in
      dephosphorylation of CREB at Ser133. These findings suggest a novel
      etiopathogenic mechanism of cognitive deficit induced by hypertension, which is
      initiated by high salt diet.

PMID- 29221167
TI  - Aggressiveness pattern and second primary tumor risk associated with basaloid
      squamous cell carcinoma of the larynx.
AB  - Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct
      variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive
      tract. We have evaluated disease specific survival (DSS) and overall survival
      (OS) through Kaplan-Meier method and mortality risk through univariate
      statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC
      (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a
      more aggressive tumor than LSCC as is associated to higher nodal recurrence of
      pathology (5 vs 2 patients, overall risk, OR 2.7), a reduced survival (median
      survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients
      have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR
      5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4).
      The analysis of survival shows an increased mortality risk concurrent with the
      parameters assessed by univariate analyses that assume a predictive and
      statistical significance in second tumor and grading in basaloid LSSC.

PMID- 29221168
TI  - Diagnosis, prognosis and bioinformatics analysis of lncRNAs in hepatocellular
      carcinoma.
AB  - This study aims to comprehensively analyze the diagnosis and prognosis of lncRNAs
      in hepatocellular carcinoma (HCC). From the Gene Expression Omnibus database, we
      screened out and analyzed the differently expressed lncRNAs and related mRNAs
      using bioinformatics methods. The expressions of lncRNAs were validated in tumor
      tissues, cell lines and the Cancer Genome Atlas database. At the same time, we
      also conducted an exploratory analysis on the diagnostic and prognostic ability
      of lncRNAs in HCC. In this study, we found that most of the targeted mRNAs
      promote the biological process of cell division, cellular component of
      nucleoplasm, molecular function of protein binding, which were significantly
      associated with 12 KEGG pathways. LncRNA CRNDE and LINC01419 also had significant
      diagnostic value in HCC. In particular, the sensitivity, specificity and area
      under the curve of CRNDE were 71.0%, 87.1% and 0.701 (95% CI: 0.543-0.860),
      respectively. In addition, the high expression of CRNDE and GBAP1 predicated poor
      prognosis, while the high expression of LINC01093 suggested the opposite outcome.
      Through the comprehensive analysis of lncRNAs, it provided an important reference
      for the early diagnosis, prognosis evaluation, pathogenesis and targeted therapy
      of HCC.

PMID- 29221169
TI  - Targeting PP2A activates AMPK signaling to inhibit colorectal cancer cells.
AB  - LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC)
      cells was tested. The in vitro studies demonstrated that LB-100 inhibited
      survival and proliferation of both established CRC cells (HCT-116 and HT-29
      lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis
      and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity
      and activated AMPK signaling in CRC cells. AMPKalpha1 dominant negative mutation,
      shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely
      attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity. Notably,
      microRNA-17-92-mediated silence of PP2A (regulatory B subunit) also activated
      AMPK and induced HCT-116 cell death. Such effects were again largely attenuated
      by AMPKalpha mutation, silence or complete knockout. In vivo studies showed that
      intraperitoneal injection of LB-100 inhibited HCT-116 xenograft growth in nude
      mice. Its anti-tumor activity was largely compromised against HCT-116 tumors
      derived from AMPKalpha1-knockout cells. We conclude that targeting PP2A by LB-100
      and microRNA-17-92 activates AMPK signaling to inhibit CRC cells.

PMID- 29221170
TI  - Proteoglycan-targeting applied to hypoxia-activated prodrug therapy in
      chondrosarcoma: first proof-of-concept.
AB  - Due to its abundant chondrogenic matrix and hypoxic tissue, chondrosarcoma is
      chemo- and radio-resistant. Our group has developed a proteoglycan targeting
      strategy by using a quaternary ammonium (QA) function as a carrier of DNA
      alkylating agents to chondrosarcoma environment. Here, we assessed the relevance
      of this strategy applied to hypoxia-activated prodrugs, by conjugating a QA to 2
      nitroimidazole phosphoramidate. This derivative, named as 8-QA, was evaluated
      respectively to its non-QA equivalent and to a QA-conjugated but non-hypoxia
      activated. Firstly binding to aggrecan was confirmed from dissociation constant
      determined by Surface Plasmon Resonance. In vitro, in HEMC-SS chondrosarcoma
      cells cultured in monolayer and in spheroids, 8-QA showed higher cytotoxic
      activity in hypoxia versus normoxia, and led to a strong accumulation of cells in
      S phase and apoptosis. In vivo, a HEMC-SS xenograft model was implanted on SCID
      mice and characterized for hypoxia by photoacoustic imaging as well as
      proteoglycan content. When HEMC-SS bearing mice were given 8-QA at 47 MUmol/kg
      according to a q4d x 6 schedule, a significant 62.1% inhibition of tumor growth
      was observed, without associated hematological side effects. Mechanistic studies
      of treated tumors highlighted decrease in mitotic index associated to increase in
      both p21 and p53S15 markers. Interestingly, 8-QA treatment induced an increase of
      DNA damages as measured by gammaH2AX predominantly found in pimonidazole-positive
      hypoxic areas. These preclinical results are the first to demonstrate the
      interest of addressing hypoxia-activated prodrugs selectively to proteoglycan of
      chondrogenic tumor tissue, as a promising therapeutic strategy.

PMID- 29221171
TI  - Proteogenomic analysis prioritises functional single nucleotide variants in
      cancer samples.
AB  - Massively parallel DNA sequencing enables the detection of thousands of germline
      and somatic single nucleotide variants (SNVs) in cancer samples. The functional
      analysis of these mutations is often carried out through in silico predictions,
      with further downstream experimental validation rarely performed. Here, we
      examine the potential of using mass spectrometry-based proteomics data to further
      annotate the function of SNVs in cancer samples. RNA-seq and whole genome
      sequencing (WGS) data from Jurkat cells were used to construct a custom database
      of single amino acid variant (SAAV) containing peptides and identified over 1,000
      such peptides in two Jurkat proteomics datasets. The analysis enabled the
      detection of a truncated form of splicing regulator YTHDC1 at the protein level.
      To extend the functional annotation further, a Jurkat phosphoproteomics dataset
      was analysed, identifying 463 SAAV containing phosphopeptides. Of these
      phosphopeptides, 24 SAAVs were found to directly impact the phosphorylation event
      through the creation of either a phosphorylation site or a kinase recognition
      motif. We identified a novel phosphorylation site created by a SAAV in splicing
      factor SF3B1, a protein that is frequently mutated in leukaemia. To our
      knowledge, this is the first study to use phosphoproteomics data to directly
      identify novel phosphorylation events arising from the creation of
      phosphorylation sites by SAAVs. Our study reveals multiple functional mutations
      impacting the splicing pathway in Jurkat cells and demonstrates potential
      benefits of an integrative proteogenomics analysis for high-throughput functional
      annotation of SNVs in cancer.

PMID- 29221172
TI  - The prognostic value of inflammation-based scores in advanced hepatocellular
      carcinoma patients prior to treatment with sorafenib.
AB  - Background and Aims: The multikinase inhibitor sorafenib is the only currently
      approved drug for the indication of advanced hepatocellular carcinoma (HCC). It
      provides a limited gain in survival time but is frequently associated with
      adverse events. We currently lack simple prognostic factors in sorafenib-treated
      HCC patients. Various inflammation-based scores (IBSs) have been evaluated as
      predictors of tumor recurrence and survival in various malignancies (including
      HCC). The objective of the present study was to determine the prognostic value of
      IBSs for overall survival (OS) in advanced HCC patients prior to the initiation
      of sorafenib therapy. Methods: Patients with Barcelona Clinic Liver Cancer stage
      C HCC were enrolled retrospectively between October 2007 and September 2015. To
      identify prognostic factors for OS, bivariate and multivariate analysis were
      performed using a Cox proportional hazards regression model. Results: 161
      patients (87.0% males; median age: 67; median OS: 9.1 months) were enrolled. A
      multivariate analysis identified a body mass index <25kg/m2 (hazard ratio
      (HR)=1.55, p<0.017), macroscopic vascular invasion (HR=1.63, p< 0.001), an AST
      level >38 U/L (HR=2.65, p<0.001), Child Pugh B stage (HR=2.59, p<0.001) and a
      systemic immune-inflammation index (SII) >=600 * 109 (HR 1.72, p=0.002) as
      independent risk factors for OS in advanced HCC. Conclusion: IBSs (such as the
      SII) are novel, simple, low-cost prognostic indices in patients with advanced
      HCC. They may be of value in determining whether these patients may benefit from
      sorafenib therapy.

PMID- 29221173
TI  - Farnesyl phenolic enantiomers as natural MTH1 inhibitors from Ganoderma sinense.
AB  - Cancer cells are more addictive to MTH1 than normal cells because of their
      dysfunctional redox regulations. MTH1 plays an important role to maintain tumor
      cell survival, while it is not indispensable for the growth of normal cells.
      Farnesyl phenols having a coumaroyl substitution are rather uncommon in nature.
      Eight farnesyl phenolic compounds with such substituent moiety (1-8), including
      six new ones, ganosinensols E-J (1-6) were isolated from the 95% EtOH extract of
      the fruiting bodies of Ganoderma sinense. Four pairs of enantiomers 1/2, 3/4, 5/6
      and 7/8 were resolved by HPLC using a Daicel Chiralpak IE column. Their
      structures were elucidated from extensive spectroscopic analyses and comparison
      with literature data. The absolute configurations of C-1' in 1-6 were assigned by
      ECD spectra. These compounds were predicted to have high binding affinity to MTH1
      through virtual ligand screening. The enzyme inhibition experiments and cell
      based assays confirmed their inhibitory effects on MTH1. Furthermore, siRNA
      knockdown experiments and the cellular thermal shift assay (CETSA) confirmed that
      the farnesyl phenolic enantiomers specifically bound with MTH1 in intact cells.
      Meanwhile, the low cytotoxicity of 1-8 on normal human cells further verified
      their good selectivity and specificity to MTH1. These active structures are
      expected to be potential anti-cancer lead compounds.

PMID- 29221174
TI  - Methylation-induced downregulation and tumor suppressive role of microRNA-29b in
      gastric cancer through targeting LASP1.
AB  - MicroRNAs (miRs) have been demonstrated to play promoting or tumor suppressive
      roles in various human cancers, but the regulatory mechanism of miR-29b
      underlying gastric cancer development and progression still remains largely
      unclear. In the present study, we found that miR-29b was significantly
      downregulated in gastric cancer tissues and cell lines. Low expression of miR-29b
      was significantly associated with DNA methylation, and treatment with DNA
      methyltransferase inhibitor 5-Aza-20-deoxycytidine upregulated miR-29b in gastric
      cancer cells. In addition, both reduced miR-29b expression and miR-29b
      methylation were associated with disease progression and poor prognosis in
      gastric cancer. Restoration of miR-29b caused a reduction in gastric cancer cell
      proliferation, migration, and invasion, and inhibited tumor growth in vivo. LASP1
      was then identified as a target gene of miR-29b in gastric cancer cells.
      Moreover, upregulation of LASP1 was significantly associated with gastric cancer
      progression and poor prognosis. Knockdown of LASP1 also suppressed the
      proliferation, migration, and invasion of gastric cancer cells. Moreover,
      overexpression of LASP1 impaired the suppressive effects of miR-29b on the
      malignant phenotypes of gastric cancer cells, suggesting that miR-29b may inhibit
      gastric cancer growth and metastasis via targeting LASP1. According to these
      data, miR-29b may be used as a potential therapeutic candidate for gastric
      cancer.

PMID- 29221175
TI  - TRPM8 is required for survival and radioresistance of glioblastoma cells.
AB  - TRPM8 is a Ca2+-permeable nonselective cation channel belonging to the melastatin
      sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly
      overexpressed in a variety of tumor entities including glioblastoma multiforme
      where it reportedly contributes to tumor invasion. The present study aimed to
      disclose further functions of TRPM8 in glioma biology in particular upon cell
      injury by ionizing radiation. To this end, TCGA data base was queried to expose
      the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was
      performed to analyze the TRPM8 protein abundance in primary cultures of human
      glioblastoma. Moreover, human glioblastoma cell lines were irradiated with 6 MV
      photons and TRPM8 channels were targeted pharmacologically or by RNA
      interference. TRPM8 abundance, Ca2+ signaling and resulting K+ channel activity,
      chemotaxis, cell migration, clonogenic survival, DNA repair, apoptotic cell
      death, and cell cycle control were determined by qRT-PCR, fura-2 Ca2+ imaging,
      patch-clamp recording, transfilter migration assay, wound healing assay, colony
      formation assay, immunohistology, flow cytometry, and immunoblotting. As a
      result, human glioblastoma upregulates TRPM8 channels to variable extent. TRPM8
      inhibition or knockdown slowed down cell migration and chemotaxis, attenuated DNA
      repair and clonogenic survival, triggered apoptotic cell death, impaired cell
      cycle and radiosensitized glioblastoma cells. Mechanistically, ionizing radiation
      activated and upregulated TRPM8-mediated Ca2+ signaling that interfered with cell
      cycle control probably via CaMKII, cdc25C and cdc2. Combined, our data suggest
      that TRPM8 channels contribute to spreading, survival and radioresistance of
      human glioblastoma and, therefore, might represent a promising target in future
      anti-glioblastoma therapy.

PMID- 29221176
TI  - Alpha-Tocopherol prevents esophageal squamous cell carcinoma by modulating
      PPARgamma-Akt signaling pathway at the early stage of carcinogenesis.
AB  - The poor prognosis of esophageal squamous cell carcinoma (ESCC) emphasizes the
      urgent need to better understand the carcinogenesis and develop prevention
      strategies. Previous studies have highlighted the potential of using Vitamin E
      (tocopherols) for cancer chemoprevention, but the preventive activity of alpha
      Tocopherol against ESCC remains to be elucidated. Our data showed that early
      stage supplementation with alpha-Tocopherol significantly prevented esophageal
      carcinogenesis induced by N-nitrosomethylbenzylamine (NMBA) in ESCC rat model. In
      the Het-1A cell model, alpha-Tocopherol markedly suppressed cell proliferation,
      promoted cell cycle G2-phase arrest and increased apoptosis. Gene microarray and
      proteins array analysis indicated that Akt signaling was a potential target for
      alpha-Tocopherol. We further demonstrated that alpha-Tocopherol increased the
      expression of PPARgamma and its downstream tumor suppressor PTEN. Knockdown of
      PPARgamma activated Akt signaling transduction, whereas this process was
      attenuated by the presence of alpha-Tocopherol and PPARgamma agonist
      Rosiglitazone. In contrast, the effect of alpha-Tocopherol on Akt inhibition was
      not observed in established tumors, neither in cancerous cell lines which
      constitutively expressed higher levels of PPARgamma. These results were closely
      correlated with the ineffectiveness of alpha-Tocopherol in the late stage of ESCC
      carcinogenesis. Taken together, our study suggested that alpha-Tocopherol may
      serve as a PPARgamma agonist for the chemoprevention of esophageal cancer.

PMID- 29221177
TI  - Untargeted serum metabonomics study of psoriasis vulgaris based on ultra
      performance liquid chromatography coupled to mass spectrometry.
AB  - Psoriasis is a common, chronic, systemic inflammatory skin disease, the etiology
      and pathogenesis is unclear. An untargeted high-throughput metabonomics method
      based on liquid chromatography coupled to mass spectrometry was applied to study
      the serum metabolic changes in psoriasis vulgaris patients, and to discover serum
      potential biomarkers for identification, diagnosis and exploring pathogenesis of
      psoriasis. The serum metabolic profiles from 150 subjects (75 psoriasis patients
      and 75 healthy controls) were acquired, the raw spectrometric data were processed
      by multivariate statistical analysis, and 44 potential biomarkers were screened
      out and identified. The potential biomarkers were mainly involved in
      glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid
      metabolism, bile acid biosynthesis, indicated the pathogenesis of psoriasis may
      be related to the disturbed metabolic pathways.

PMID- 29221179
TI  - Marital status is associated with superior survival in patients with esophageal
      cancer: a Surveillance, Epidemiology, and End Results study.
AB  - The impact of marital status on survival among patients with esophageal cancer
      has not been evaluated in the U.S. population in depth. The aim of the study was
      to investigate the impact of marital status on survival among patients diagnosed
      with esophageal cancer. The Surveillance, Epidemiology, and End Results (SEER)
      database was utilized to identify patients diagnosed with esophageal cancer
      between 1973 and 2013. Cox regression analysis was performed to evaluate for
      association between marital status on both cancer-specific and overall survival.
      Of the 69,139 patients with esophageal cancer, 35,863 (52%) had adenocarcinoma
      and 21,573 (31%) had distant SEER stage. At the time of diagnosis, 39,805 (57%)
      patients were married, 10,116 (15%) were single, 8,417 (12%) were divorced or
      separated, and 10,801 (16%) were widowed. Married patients had superior cancer
      specific and overall survival compared to unmarried patients. Multivariate
      analysis demonstrated that single (adjusted hazard ratio (HR)=1.14, 95%CI 1.11
      1.17; P<0.001), divorced or separated (HR=1.16, 95%CI 1.13-1.19; P<0.001), and
      widowed (HR=1.22, 95%CI 1.19-1.26; P<0.001) compared to married patients had
      higher risk of death from all causes. In conclusion, marital status was
      associated with superior survival among U.S. patients with esophageal cancer in a
      large population-based study.

PMID- 29221178
TI  - Cytotoxic stress induces transfer of mitochondria-associated human endogenous
      retroviral RNA and proteins between cancer cells.
AB  - About 8 % of the human genome consists of human endogenous retroviruses (HERVs),
      which are relicts of ancient exogenous retroviral infections incurred during
      evolution. Although the majority of HERVs have functional gene defects or
      epigenetic modifications, many of them are still able to produce retroviral
      proteins that have been proposed to be involved in cellular transformation and
      cancer development. We found that, in chemo-resistant U87RETO glioblastoma cells,
      cytotoxic stress induced by etoposide promotes accumulation and large-scale
      fission of mitochondria, associated with the detection of HERV-WE1 (syncytin-1)
      and HERV-FRD1 (syncytin-2) in these organelles. In addition, mitochondrial
      preparations also contained the corresponding receptors, i.e. ASCT2 and MFSD2. We
      clearly demonstrated that mitochondria associated with HERV-proteins were
      shuttled between adjacent cancer cells not only via tunneling tubes, but also by
      direct cellular uptake across the cell membrane. Furthermore, anti-syncytin-1 and
      anti-syncytin-2 antibodies were able to specifically block this direct cellular
      uptake of mitochondria even more than antibodies targeting the cognate receptors.
      Here, we suggest that the association of mitochondria with syncytin-1/syncytin-2
      together with their respective receptors could represent a novel mechanism of
      cell-to-cell transfer. In chemotherapy-refractory cancer cells, this might open
      up attractive avenues to novel mitochondria-targeting therapies.

PMID- 29221180
TI  - Pelvic recurrence after definitive surgery for locally advanced rectal cancer: a
      retrospective investigation of implications for precision radiotherapy field
      design.
AB  - Background: To analyze the local distribution of pelvic recurrence after total
      mesorectal excision, with a view to simplifying the formulation of optimal
      individualized radiotherapy plans. Methods: We retrospectively investigated the
      data of 168 patients diagnosed with recurrent pelvic cancer treated at Fudan
      University Shanghai Cancer Center between January 2008 and December 2012. The
      following were collected depending on availability: operative report,
      histological report, specimen photographs, initial preoperative images, images
      confirming local recurrence, and clinical history. Results: A total of 203
      lesions of local recurrence were identified. The most common sites of pelvic
      recurrence were the mesorectum, including the anastomotic stoma in 53.0% of
      cases; presacral space in 27.4%, and pelvic floor and perineum in 21.4% the
      cases. Recurrence was most common in the lower pelvic region (i.e., below the
      upper border of the acetabulum), accounting for approximately 76.2% (128 cases)
      of cases. In patients with mid-rectal and distal rectal carcinoma. Conclusions:
      Patients with pelvic cancer may benefit by individualized treatment plans aimed
      at achieving a balance between tumor control and minimal risk of irradiation
      induced toxicity.

PMID- 29221181
TI  - Analysis of CTCL cell lines reveals important differences between mycosis
      fungoides/Sezary syndrome vs. HTLV-1+ leukemic cell lines.
AB  - HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers
      it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and
      present with classic erythematous pruritic patches and plaques that are typically
      seen in Mycosis Fungoides (MF) and Sezary Syndrome (SS), the most recognized
      variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1
      in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed
      CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping,
      extensive gene expression analysis, TP53 sequencing in the 11 patient-derived
      HTLV-1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4
      and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used
      CTCL therapies and studied the ability of these cells to produce subcutaneous
      xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates
      that unlike classic advanced MF/SS cells that acquire many ongoing balanced and
      unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid
      and exhibit only a minimal number of non-specific chromosomal alterations. Our
      results indicate that HTLV-1 virus is likely not involved in the pathogenesis of
      classic MF/SS since it drives a very different pathway of lymphomagenesis based
      on our findings in these cells. This study also provides for the first time a
      comprehensive characterization of the CTCL cells with respect to gene expression
      profiling, TP53 mutation status, ability to produce tumors in mice and response
      to commonly used therapies.

PMID- 29221182
TI  - Differential modulation of Bax/Bcl-2 ratio and onset of caspase-3/7 activation
      induced by derivatives of Justicidin B in human melanoma cells A375.
AB  - Diphyllin and its derivatives are well known cytotoxic natural products
      structurally related to the anti-cancer drug podophyllotoxin. We here study their
      structure-activity relationship upon human melanoma cells for first time. To this
      end, human melanoma A375 cells were incubated with Justicidin B and its 4
      methoxylated or 4-glycosylated derivatives to evaluate their selective
      cytotoxicity and study their effects on cell cycle distribution, caspase
      activation, apoptosis induction using Annexin V-FITC/PI staining, cell morphology
      and western blot analysis. Diphyllin methyl ether (GI50 = 3.66 MUM) and
      Justicidin B (GI50 = 1.70 MUM) caused an elevation of both early and late
      apoptosis populations whereas Diphyllin apioside (GI50 = 0.84 MUM) and its
      acetate (GI50= 0.39 MUM) enhanced late apoptosis population only (Annexin V
      positive/PI-positive). All induced cell cycle arrest at S phase and classic
      morphological indicators of apoptosis (blebbing, apoptotic bodies, and nuclear
      fragmentation) accompanied with an elevation of cells with low DNA content (sub
      G1). All compounds increased the Bax/Bcl-2 ratio by enhancing Bax expression
      which evidences the involvement of the mitochondria (intrinsic pathway) in the
      apoptotic process. These caspase-3/7 results evidence that 4-methoxylation or 4-O
      glycosylation of Justicidin B -a caspase independent mitochondrial apoptosis
      inducer- triggers caspase-3/7 activation at different times (24h vs. 48h,
      respectively). Interestingly, the methoxylation causes attenuation of Bcl-2
      protein expression contrarily to Diphyllin methyl ether or the O-glycosylated
      derivatives. Finally, the compounds exhibited significantly less toxicity when
      tested in adult human dermal fibroblasts and their GI50 in melanoma Sk-Mel-5
      cells was not influenced by MDR1/Pgp inhibitors. This study may inform the
      synthesis of future Diphyllin derivatives with different apoptosis mechanism of
      action towards human melanoma cells.

PMID- 29221183
TI  - Radial gradient and radial deviation radiomic features from pre-surgical CT scans
      are associated with survival among lung adenocarcinoma patients.
AB  - The goal of this study was to extract features from radial deviation and radial
      gradient maps which were derived from thoracic CT scans of patients diagnosed
      with lung adenocarcinoma and assess whether these features are associated with
      overall survival. We used two independent cohorts from different institutions for
      training (n= 61) and test (n= 47) and focused our analyses on features that were
      non-redundant and highly reproducible. To reduce the number of features and
      covariates into a single parsimonious model, a backward elimination approach was
      applied. Out of 48 features that were extracted, 31 were eliminated because they
      were not reproducible or were redundant. We considered 17 features for
      statistical analysis and identified a final model containing the two most highly
      informative features that were associated with lung cancer survival. One of the
      two features, radial deviation outside-border separation standard deviation, was
      replicated in a test cohort exhibiting a statistically significant association
      with lung cancer survival (multivariable hazard ratio = 0.40; 95% confidence
      interval 0.17-0.97). Additionally, we explored the biological underpinnings of
      these features and found radial gradient and radial deviation image features were
      significantly associated with semantic radiological features.

PMID- 29221184
TI  - Hepatitis B virus X protein inhibits apoptosis by modulating endoplasmic
      reticulum stress response.
AB  - Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular
      carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of
      the four open reading frames of HBV, and is well known as an important
      coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis.
      However, its role in keeping cells from apoptosis to promote HCC proliferation
      remains controversial. Here, we used HBx expressing HCC cells as a model, to
      investigate the mechanism of HBx-mediated cellular response to endoplasmic
      reticulum (ER) stress. We found that HBx protein was localized in ER lumen and
      interacted with GRP78 directly. This interaction resulted in suppression of
      eIF2alpha phosphorylation, inhibited expression of ATF4/CHOP/Bcl-2, and reduced
      cleavage of poly ADP-ribose polymerase (PARP) and level of gammaH2AX, thus
      preventing HCC cells from cell death and negatively regulating DNA repair. This
      study reveals a novel mechanism of the HBx-mediated oncogenesis and provides a
      basis for potential HBx-targeted therapeutic intervention of HCC.

PMID- 29221185
TI  - TGFbeta1 in fibroblasts-derived exosomes promotes epithelial-mesenchymal
      transition of ovarian cancer cells.
AB  - Cancer-associated fibroblasts (CAF), a major component of the tumor
      microenvironment, play an important role in interacting with neoplastic cells to
      promote ovarian cancer progression. Exosomes are nano-sized vesicles that mediate
      the cross-talk between different cell types. An increasing number of studies have
      focused on the fact that tumor cell-derived exosomes influence stromal cells.
      However, the mechanism by which CAF-derived exosomes modulate cancer cells in
      ovarian cancer remains obscure. To investigate the role of CAF exosomes in
      ovarian cancer, we examined the exosomal content of paired primary, metastatic
      and normal fibroblasts from seven stage IIIC ovarian cancer patients by ELISA. We
      found that in ovarian CAF-derived exosomes, TGFbeta1 was upregulated compared to
      normal omentum fibroblasts (NOF). Exosomes derived from CAF were taken up by
      ovarian SKOV-3 and CAOV-3 cell lines during co-culture and induced malignant
      behaviors in cancer cells, including an enhanced migration and invasion ability
      and the promotion of epithelial-mesenchymal transition (EMT) by activating the
      SMAD signaling pathway. Our results indicate that the role of TGFbeta1 in CAF
      exosomes triggers ovarian cancer cells into a more aggressive phenotype,
      suggesting that targeting CAF exosomes could be a potential treatment in ovarian
      cancer.

PMID- 29221186
TI  - Inflammatory biomarkers in metastatic colorectal cancer: prognostic and
      predictive role beyond the first line setting.
AB  - Introduction: Inflammatory biomarkers are useful prognostic tools in cancer
      patients. However, the prognostic and predictive value of inflammatory biomarkers
      beyond the 1st-line setting in metastatic colorectal cancer (mCRC) is unclear.
      Results: In multivariate analysis 1 standard deviation increase in neutrophil
      lymphocyte-ratio (NLR) was associated with an 8.5% absolute lower objective
      response-rate (ORR) in 1st-line (p<0.0001), 3% lower ORR in 2nd-line (p< 0.0001),
      and 3% lower ORR in 3rd-line (p=0.24), respectively. Regarding progression free
      survival (PFS), an increase in the NLR was significantly associated with rising
      hazard-ratios (HR) over all treatment lines (HR=1.30, p= 0.021 1st-line);
      (HR=1.37, p<0.0001 2nd-line); (HR=1.44, p=0.042 3rd-line). The platelet
      lymphocyte-ratio (PLR) was associated with 6-month PFS over all three treatment
      lines. Higher C-reactive-protein (CRP) predicted for worse PFS in the first two
      chemotherapy lines and in best supportive care (BSC). (HR=1.49 (p<0.0001 1st
      line); HR=1.25 (p=0.007 2nd-line); HR=1.09 (95%CI 0.81-1.48, p=0.552 3rd-line and
      HR=1.43 (p= 0.002 in BSC)). Methods: Two-hundred-fifty-eight patients with mCRC
      undergoing palliative chemo(immuno-)therapy were retrospectively included.
      Primary endpoints were 6-month PFS and ORR during 1st-line, 2nd-line, and 3rd
      line treatment, and 6-month overall survival during BSC. Conclusion: This study
      shows that inflammatory biomarkers are useful predictors of disease outcome and
      treatment response over several treatment lines in mCRC patients.

PMID- 29221187
TI  - Selection and characterization of a human ovarian cancer cell line resistant to
      auranofin.
AB  - The anti-arthritic drug auranofin exerts also potent antitumour activity in in
      vitro and in vivo models, whose mechanisms are not yet well defined. From an
      auranofin-sensitive human ovarian cancer cell line A2780, a highly resistant (>20
      fold) subline (A2780/AF-R) was developed and characterized. Marked reduction of
      gold accumulation occurred in auranofin-resistant A2780 cells. Also, moderately
      higher thioredoxin reductase activity in A2780/AF-R cells was observed while no
      changes in intracellular glutathione content occurred. Resistance to auranofin
      was associated with a low level of cross-resistance to some investigational gold
      compounds as well as to oxaliplatin and other anticancer drugs with different
      mode of action (i.e. melphalan, vinblastine, doxorubicin, etoposide, and
      paclitaxel). Reduced gold accumulation was associated to substantial gene
      expression changes in various influx (e.g. SLC22A1, SLC47A1, SLCO1B1) and efflux
      (e.g. ABCB1, ABCC2, ABCC3) transporters. The expression levels of selected
      proteins (i.e. SLC22A1, SLC47A1, P-gp) were also changed accordingly. These data
      provide evidence that multiple drug transporters may act as mediators of
      transport of auranofin and other gold compounds in cancer cells. Further
      investigation into the molecular mechanisms mediating transport of auranofin and
      new gold complexes in view of their potential clinical application in the
      treatment of cancer is warranted.

PMID- 29221188
TI  - Overexpression of AGT promotes bronchopulmonary dysplasis via the JAK/STAT signal
      pathway.
AB  - Angiotensinogen (AGT) is involved in the production of angiotensin II which is
      the main mediator of action of the rennin-angiotensin system (RAS), whereas the
      RAS mediates the regulation of sodium homeostasis, blood pressure, and
      inflammation. The present study aimed to investigate the roles of the AGT in the
      progression of broncopulmonary dysplasia in premature newborns. By bioinformatics
      analysis, AGT was found to be the major node in molecular interaction networks of
      BPD mouse model. Quantitative PCR and western blot analyses were applied to
      examine AGT expression in A549 cells which were treated with the hyperoxic
      condition. The AGT inhibitor Valsartan and the AGT agonist ANGII were employed to
      investigate the roles of AGT in cell growth and the inflammation. Results show
      that hyperoxic treatment induced upregulation of AGT expression in A549 cells.
      Overexpression of AGT resulted in the inflammation via the JAK/STAT signal
      pathway, ultimately suppressed the proliferation of the A549 cell. In conclusion,
      increased expression of AGT was demonstrated to be associated with the
      development and progression of BPD, and may be regarded as a promising
      therapeutic target for BPD.

PMID- 29221190
TI  - The M6A methyltransferase METTL3: acting as a tumor suppressor in renal cell
      carcinoma.
AB  - We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis
      and development. Immunohistochemistry was performed in clinical tissue
      microarray. Expression level of METTL3 in RCC tissues and cell lines was
      evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the
      effects of METTL3 on proliferation, migration, invasion and cell cycle were
      studied in RCC cells. Additionally, in vivo study was carried out in nude mice.
      Negative METTL3 expression was associated with larger tumor size (P=0.010) and
      higher histological grade (P=0.021). Moreover, RCC patients with positive METTL3
      expression had an obvious longer survival time (P=0.039). METTL3 mRNA and protein
      expression was lower in RCC samples compared with adjacent non-tumor samples, and
      lower in RCC cell lines (CAKI-1, CAKI-2 and ACHN) compared with HK-2. Afterwards,
      knockdown of METTL3 could obviously promote cell proliferation, migration and
      invasion function, and induce G0/G1 arrest. In contrast, up-regulation of METTL3
      could inhibit such functions and reduce G0/G1 arrest. Additionally, up-regulation
      of METTL3 significantly suppressed tumor growth in vivo. Furthermore, significant
      changes in epithelial-to-mesenchymal transition (EMT) and PI3K-Akt-mTOR pathways
      were observed. Overall, our findings demonstrated that METTL3 might have a
      carcinostasis role in cell proliferation, migration, invasion function and cell
      cycle of RCC, indicating METTL3 may act as a novel marker for tumorigenesis,
      development and survival of RCC.

PMID- 29221189
TI  - Novel direct AMPK activator suppresses non-small cell lung cancer through
      inhibition of lipid metabolism.
AB  - Drug resistance is becoming an obstacle in anti-cancer therapies. For target
      based therapy of lung cancer, gefitinib, as the first generation of tyrosine
      kinase inhibitors (TKIs), demonstrated good initial response to the non-small
      cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor
      (EGFR) mutation. However, within one year, additional EGFR mutation occurred,
      leading to eventual gefitinib-resistance. Therefore, it is urgently to discover
      novel effective small molecule inhibitors for those patients. Abnormal energy
      metabolism is accepted as new cancer hallmark. Recently, a metabolism rate
      limiting enzyme 5'-adenosine menophosphate-activated protein kinase (AMPK) has
      become a promising anti-cancer target. In this study, we have identified a novel
      direct AMPK agonist, D561-0775 from a compound library by using molecular docking
      screening technique. We demonstrated that D561-0775 exhibited significant
      inhibitory effect on gefitinib-resistant NSCLC cell lines but less cytotoxicity
      on normal cells. Furthermore, D561-0775 demonstrated a remarkable in vitro AMPK
      enzyme activation effect. Taken together, D561-0775 showed potential anti-cancer
      activity via inducing apoptosis, cell cycle arrest, suppressing glycolysis and
      cholesterol synthesis after activation of AMPK in gefitinib-resistant H1975
      cells. D561-0775 has provided a new chemical structure that could be developed as
      cancer drug for gefitinib-resistant NSCLC patients through inhibition lipid
      metabolism by directly targeting at AMPK directly.

PMID- 29221191
TI  - Recommended oral sodium bicarbonate administration for urine alkalinization did
      not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer
      patients.
AB  - Objective: Sodium bicarbonate has been reported to maximize the efficacy of
      intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine
      alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to
      analyze the changes in MMC concentration according to urinary pH and evaluate the
      efficacy of sodium bicarbonate to maintain the concentration of active form of
      MMC during IVI-MMC. Methods: We prospectively enrolled 26 patients with NMIBC
      after transurethral resection of bladder tumor. Patients with very high-risk and
      low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations
      of MMC and its degraded form were measured immediately before and after IVI-MMC.
      The patients were administered 1.5 g of oral sodium bicarbonate during the
      preceding evening, in the morning, and immediately before the fourth cycle of the
      six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH
      changes was explored with or without oral bicarbonate therapy. Results:
      Recurrence without progression to muscle-invasive disease was noted in 4 of 26
      patients in a 23.7-month follow-up. The mean urinary pH before and after the
      therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB
      therapy, respectively. Despite this increase, the concentration of active form of
      MMC did not change significantly. No correlation was found between urinary pH and
      MMC concentration. Urine alkalinization by SB administration did not maintain the
      high concentration of urinary MMC. Conclusions: Urine alkalinization by sodium
      bicarbonate administration for IVI-MMC did not maintain the high concentration of
      active urinary MMC in NMIBC.

PMID- 29221192
TI  - Tumor-suppressive function of UNC5D in papillary thyroid cancer.
AB  - Background: Studies have shown an association of the UNC5D gene with kidney and
      bladder cancer and neuroblastoma. We investigated whether UNC5D acts as a tumor
      suppressor in papillary thyroid carcinoma (PTC). Methods: Primary PTC tumors and
      matched normal thyroid tissues were obtained from 112 patients to detect UNC5D
      mRNA by real-time PCR. Genomic DNA sequencing was performed to detect BRAF
      mutation in PTC tumors. The association between UNC5D expression and
      clinicopathological data from PTC patients was reviewed retrospectively. PTC
      derived cancer cell lines TPC-1 and K1 with stable transfection of UNC5D were
      used to investigate the functions of UNC5D. Flow cytometry, CCK-8, Transwell
      assay and scratch tests were used to examine cell cycle distribution,
      proliferation and migration. Results: The expression of UNC5D was significantly
      decreased in PTC compared with adjacent normal thyroid tissues. Lower UNC5D
      expression was significantly associated with aggressive tumor behaviors, such as
      lymph node metastasis and BRAF mutation. Overexpression of UNC5D significantly
      suppressed malignant cell behaviors, including cell proliferation and migration,
      as well as tumor growth in vivo. Conclusions: These findings suggest a potential
      tumor suppressor role of UNC5D in PTC progression; and provide insight into
      potential clinical relevance for the prognosis of PTC.

PMID- 29221193
TI  - Steroidogenic factor-1 hypermethylation in maternal rat blood could serve as a
      biomarker for intrauterine growth retardation.
AB  - Intrauterine growth retardation (IUGR) is a common obstetric complication lacking
      an optimal method for prenatal screening. DNA methylation profile in maternal
      blood holds significant promise for prenatal screening. Here, we aimed to screen
      out potential IUGR biomarkers in maternal blood from the perspective of DNA
      methylation. The IUGR rat model was established by prenatal maternal
      undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation
      followed by functional clustering analysis for differentially methylated region
      (DMR)-associated genes demonstrated that genes regulating transcription had the
      most significantly changed DNA methylation status in maternal blood with IUGR.
      Genes about apoptosis and placental development were also changed. Besides
      increased placental apoptosis, IUGR rats demonstrated the same hypermethylated
      CpG sites of steroidogenic factor-1 (SF-1, a DMR-associated transcription factor
      about placenta) promoter in maternal blood and placentae. Further, ff1b, the SF-1
      ortholog, was knocked out in zebrafish by CRISPR/Cas9 technology. The knock-out
      zebrafish demonstrated developmental inhibition and increased IUGR rates, which
      confirmed the role of SF-1 in IUGR development. Finally, hypermethylated SF-1 was
      observed in human maternal blood of IUGR. This study firstly presented distinct
      DNA methylation profile in maternal blood of IUGR and showed hypermethylated SF-1
      could be a potential IUGR biomarker in maternal rat blood.

PMID- 29221194
TI  - Altered microRNA profiles during early colon adenoma progression in a porcine
      model of familial adenomatous polyposis.
AB  - MicroRNAs are dysregulated in various cancers including colorectal cancer, and
      are potential useful biomarkers of disease development. We used next generation
      sequencing to investigate miRNA expression profiles in low- and high-grade
      intraepithelial dysplastic polyps from pigs carrying a mutation in the
      adenomatous polyposis coli tumour suppressor (APC1311 , orthologous to human
      APC1309 ) that model an inherited predisposition to colorectal cancer, familial
      adenomatous polyposis. We identified several miRNAs and their isomiRs
      significantly (P < 0.05) differentially expressed between low and high-grade
      intraepithelial dysplastic polyps. Of these, ssc-let-7e, ssc-miR-98, ssc-miR-146a
      5p, ssc-miR-146b, ssc-miR-183 and ssc-miR-196a were expressed at higher level and
      ssc-miR-126-3p at lower level in high-grade intraepithelial dysplastic polyps.
      Functional miRNA target analysis revealed significant (P < 0.001) over
      representation of cancer-related pathways, including 'microRNAs in cancer',
      'proteoglycans in cancer', 'pathways in cancer' and 'colorectal cancer'. This is
      the first study to reveal miRNAs associated with premalignant transformation of
      colon polyps.

PMID- 29221195
TI  - Quantification of contractile mechanics in the rat heart from ventricular
      pressure alone.
AB  - To quantitate the contractile mechanics of the heart, the ventricle is considered
      an elastic chamber with known end-systolic elastance (Ees ). Ees can be
      calculated from a single pressure-ejected volume curve, which requires
      simultaneous records of left ventricular (LV) pressure and the aortic flow (Qm).
      In clinical settings, it is helpful to evaluate patients' cardiac contractile
      status by using a minimally invasive approach to physiological signal monitoring,
      wherever possible, such as by using LV pressure alone. In this study, we
      evaluated a method for determining Ees on the basis of the measured LV pressure
      and an assumed aortic flow with a triangular wave shape (Qtri). Qtri was derived
      using a fourth-order derivative of the LV pressure to approximate its
      corresponding Qm. Values of EestriQ obtained using Qtri were compared with those
      of EesmQ obtained from the measured Qm. Healthy rats (NC; n = 28) and rats with
      type 1 diabetes (DM; n = 26) and chronic kidney disease (CKD; n = 20) were
      examined. The cardiodynamic conditions in both the DM and CKD groups were
      characterized by a decline in EesmQ and EestriQ. A significant regression line
      for Ees was observed (P < 0.0001): EestriQ = 2.6214 + 1.0209 * EesmQ (r2 =
      0.9870; n = 74). Our finding indicates that the systolic pumping mechanics of the
      heart can be derived from a single LV pressure recording together with the
      assumed Qtri.

PMID- 29221196
TI  - Identification of cellular genes and pathways important for tumorigenicity of
      hepatocellular carcinoma cell lines by proteomic profiling.
AB  - Hepatocellular carcinoma (HCC) is the most commonly diagnosed malignancy of the
      liver. A more thorough understanding of HCC pathogenesis will provide novel
      targets for development of cancer drugs to effectively treat HCC. To further this
      goal, we carried out a proteomic profiling of HCC cell lines Huh-7.4 and Huh-7.5.
      These two cell lines were derived from subgenomic HCV RNA-replicating Huh-7 cells
      upon clearance of HCV RNA by antiviral drug treatment. Initially, the
      tumorigenicity of each cell line was determined and compared in parallel in the
      same immunedeficient mice. Strikingly, the Huh-7.4 cell line was able to induce
      tumors, whereas the Huh-7.5 cell line failed to do so, providing unique model
      systems for identifying cellular genes and pathways important for HCC development
      and progression. Subsequently, one-dimensional LC-MS/MS proteomic and
      bioinformatics analyses were performed in the hope of identifying unique cellular
      genes and pathways responsible for HCC tumorigenicity. Interestingly, a total of
      130 cellular genes were found to be significantly up- or downregulated between
      these two cell lines (r>3 fold, P<0.001). Also, EIF (EIF2&4), mTOR/p70S6K, ERK5,
      and EGFR signaling pathways were significantly different. Overall, these results
      provide significant new information to shed light on the underlying biological
      processes involved in HCC development and progression.

PMID- 29221197
TI  - RANK expression in EBV positive nasopharyngeal carcinoma metastasis: a ready-to
      treat target?
AB  - Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly
      chemo- and radiosensitive endemic malignancy in southeast Asia. More than one
      third of locally advanced cases relapse after curative treatment, especially
      because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV
      associated carcinogenesis and tumour progression and several strategies aim to
      reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand
      (RANKL), key regulator of bone metabolisms, are expressed in several malignancies
      and tumor-infiltrating Tregs. We collected 17 paired FFPE specimen of primary and
      metachronous metastatic or regionally relapsed EBV related NPC and evaluated RANK
      expression by immunohistochemistry. All primary tumour specimens resulted not
      evaluable whereas all metastatic specimens, regardless of sites, showed high RANK
      IHC expression in the tumor with no staining in normal surrounding tissues. This
      observation deserves further clarifications and could open the way to trials
      testing the hypotesis that targeting the RANK/RANKL pathway with denosumab, an
      already available, clinically approved monoclonal antibody for metastatic bone
      lesions, might restore proper anti-tumor immune response in NPC metastatic
      patients.

PMID- 29221198
TI  - The prognostic significance of celiac lymph node metastasis in patients with
      locally advanced esophageal squamous cell carcinoma receiving curative concurrent
      chemoradiotherapy.
AB  - Background: To evaluate the clinical outcomes of celiac lymph node (LN)
      metastasis in patients with locally advanced esophageal squamous cell carcinoma
      (ESCC) receiving curative concurrent chemoradiotherapy (CCRT). Materials and
      Methods: A total of 375 stage III ESCC patients were identified, including 51
      patients with celiac LN metastasis and 324 patients without celiac LN metastasis.
      Among these 324 patients without celiac LN metastasis, 51 were matched with the
      51 patients with celiac LN metastasis using the propensity score matching method.
      Results: Overall, the celiac LN metastasis group had worse progression-free
      survival (PFS) and overall survival (OS) than the non-celiac LN metastasis group
      and the matched non-celiac LN metastasis group. For the ESCC patients with celiac
      LN metastasis, lower third ESCC was significantly associated with superior PFS
      and OS. For patients with upper/middle third ESCC, the celiac LN metastasis group
      had worse PFS and OS than the non-celiac LN metastasis group and the matched non
      celiac LN metastasis group. For patients with lower third ESCC, there were no
      significant differences in PFS and OS between these groups. Conclusions: Our
      study suggests celiac LN metastasis is a poor prognostic factor for locally
      advanced ESCC patients receiving curative CCRT. Among these ESCC patients with
      celiac LN metastasis, tumor location is a strongly prognostic factor, indicating
      patients with lower third ESCC have better PFS and OS than those with
      upper/middle third ESCC. The 6th American Joint Committee on Cancer staging
      system seems more favorable than 7th edition in the definition of celiac LNs for
      those patients.

PMID- 29221200
TI  - Oncogene TUBA1C promotes migration and proliferation in hepatocellular carcinoma
      and predicts a poor prognosis.
AB  - The prognostic biomarkers and potential therapy targets are urgently needed in
      hepatocellular carcinoma (HCC). In this article, we report the expression of
      TUBA1C was significantly increased in HCC on mRNA and protein level, and this
      finding was further validated in another two independent datasets. Survival
      analysis was also implemented on these three datasets, and TUBA1C high expression
      group was detected to have relative shorter survival time. Furthermore, the
      metastatic ability is increased along with TUBA1C abundance, according to protein
      abundance evaluation of normal-tumor-portal vein tumor thrombus pairs, and mRNA
      comparison between metastasis-averse HCC and metastasis-incline HCC. Correlation
      analysis was implemented and TUBA1C expression was shown to be significantly
      associated with recurrence, embolus, and AFP level. Proliferation and migration
      assays following knock down of TUBA1C in two cell lines, HCCLM3 and PLC, revealed
      that down-regulation of TUBA1C significantly reduces proliferation and migration
      in HCC cells. in vivo study also showed the similar results. Gene Set Enrichment
      Analysis (GSEA) comparing the TUBA1C-low and TUBA1C-high group indicates that
      KEGG pathways including "cell cycle", "DNA replication", and "proteasome" were
      significantly enriched in TUBA1C-high group. In conclusion, prognostic biomarker
      and oncogene TUBA1C promotes migration and proliferation of hepatocellular
      carcinoma cells, probability via cell cycle signaling pathway.

PMID- 29221199
TI  - Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes
      tumorigenesis via regulating AKT/GSK-3beta signaling pathway in
      cholangiocarcinoma.
AB  - Long non-coding RNAs (lncRNAs) have been documented to play key roles in a wide
      range of pathophysiological processes, including cancer initiation and
      progression. Recently, the aberrant expression of urothelial carcinoma associated
      1 (UCA1) was observed in many types of cancers. However, its clinical relevance
      and exact effects in cholangiocarcinoma (CCA) remains unknown. In the present
      study, we aimed to investigate the clinical significance of UCA1 and evaluate its
      prognostic value in patients with CCA. Besides, the functional roles of UCA1 were
      detected both in vitro and in vivo. Moreover, potential signaling pathways were
      explored to clarify the molecular mechanisms underlying CCA cell proliferation.
      The results indicated that UCA1 transcription is enhanced in both CCA tissue
      samples and cell lines, and this overexpression is associated with tumor stage (P
      = 0.007), lymph node invasion (P = 0.027), TNM stage (P = 0.004) and
      postoperative recurrence (P = 0.033) of CCA patients. Besides, UCA1 could
      function as an independent prognostic predictor for overall survival in patients
      with CCA (P = 0.014). For the part of functional assays, knockdown of UCA1 could
      attenuate CCA cell growth both in vitro and in vivo. Besides, UCA1 facilitates
      apoptosis via Bcl-2/caspase-3 pathway. In addition, UCA1 regulates migration and
      invasion potential of CCA cells by affecting EMT. Furthermore, AKT/GSK-3beta axis
      was activated to upregulate CCND1 expression due to overexpression of UCA1 in
      CCA. To summary, UCA1 might be a potentially useful prognostic biomarker and
      therapeutic target for CCA.

PMID- 29221201
TI  - Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell
      carcinoma susceptibility.
AB  - Aberrations of the fibroblast growth factor receptor 4 (FGFR4) genomic region
      include amplification of FGFR4, activation of FGFR4 kinase domain mutations, and
      overexpression of FGFR4, which lead to sustained cell proliferation and
      contribute to tumor development. However, the association between FGFR4 single
      nucleotide polymorphisms (SNPs) and risk of oral squamous cell carcinoma (OSCC)
      remains to be determined. We investigated the relationships between FGFR4 genetic
      polymorphisms, OSCC development and clinicopathological variables. We recruited a
      total of 955 patients with OSCC and 1191 controls. Four SNPs of FGFR4 (rs2011077,
      rs351855, rs7708357, and rs1966265) were examined using real-time polymerase
      chain reaction. We found that with the rs351855 GA genotype and a combination of
      the GA and AA genotypes exhibited a 1.431-fold (95% CI: 1.092-1.876) and 1.335
      fold (95% CI: 1.033-1.725) higher risk of OSCC. However, patients with OSCC with
      a homozygous A/A genotype of FGFR4 rs351855 polymorphism had a lower risk of
      advanced stage OSCC (P = 0.0252). Furthermore, the patients with the FGFR4
      rs351855/rs1966265 A-A haplotype had a 2.890-fold (95% confidence interval [CI]:
      2.257-3.700) higher risk of OSCC than the controls. Betel quid chewers with the A
      A haplotype had a considerably higher risk (95% CI: 16.159-26.937) of OSCC than
      did betel quid nonchewers with other haplotypes. Moreover, an additional
      integrated in silico analysis proposed that rs351855 G allele variant to the A
      allele exhibited a relatively low energy of the transmembrane region. In
      conclusion, our results suggest that the FGFR4 rs351855 may play a role in
      susceptibility for OSCC development.

PMID- 29221202
TI  - EZH2 alteration driven by microRNA-524-5p and microRNA-324-5p promotes cell
      proliferation and temozolomide resistance in glioma.
AB  - Recent data have been shown that EZH2 is a critical oncogene via the repression
      of tumor suppressor genes in human cancers. In our study, we performed a genome
      wide miRNA screen with a bioinformatics analysis to identify EZH2 specific
      miRNAs. Of these miRNAs, miR-524-5p and miR-324-5p were decreased in glioma
      tissues, and confered poor prognosis for glioma patients. Upregulation of miR-524
      5p and miR-324-5p reduced glioma cell proliferation and increased temozolomide
      (TMZ) chemosensitivity by targeting EZH2. Importantly, the effection of miR-524
      5p and miR-324-5p on cell proliferation and TMZ chemosensitivity in glioma were
      reversed by expression of EZH2 cDNA. Further, miR-524-5p and miR-324-5p
      overexpression suppressed glioma growth and prolonged survival in an intracranial
      xenograft model. Multivariate Cox regression analysis revealed that miR-524-5p
      was an independent prognostic factor in gliobalstoma patients. Taken together,
      these data indicate that miRNA-driven EZH2 repression may provide evidence of the
      molecular mechanism for gliomagenesis and the novel therapeutic targets for
      glioma.

PMID- 29221203
TI  - Methylated claudin-11 associated with metastasis and poor survival of colorectal
      cancer.
AB  - As one of crucial epigenetic modification, DNA methylation plays an important
      role during the carcinogenesis of colorectal cancer (CRC). In the current study,
      we used a human genome methylation array to detect the aberrant methylation genes
      in CRC. We further identified the hypermethylation of claudin-11 (CLDN11) and
      proved inverse correlation between CLDN11 methylation and its expression in CRC.
      In vitro experiments showed debased migration ability of colonic cancer cells in
      accompany with the converted methylation of CLDN11 after colonic cancer cells
      treated with demethylation agent, 5-aza-2'-deoxycytidine. Besides, our results
      also represented that hypermethylation of CLDN11 was associated with increased
      metastatic potential of CRC and with low progression free survival (PFS) of CRC.
      In conclusion, our findings supported that the hypermethylated CLDN11 is
      associated with metastasis of CRC and prognosis of poor survival of CRC.

PMID- 29221204
TI  - 11beta-HSD1 inhibition ameliorates diabetes-induced cardiomyocyte hypertrophy and
      cardiac fibrosis through modulation of EGFR activity.
AB  - 11beta-HSD1 has been recognized as a potential therapeutic target for type 2
      diabetes. Recent studies have shown that hyperglycemia leads to activation of
      11beta-HSD1, increasing the intracellular glucocorticoid levels. Excess
      glucocorticoids may lead to the clinical manifestations of cardiac injury.
      Therefore, the aim of this study is to investigate whether 11beta-HSD1 activation
      contributes to the development of diabetic cardiomyopathy. To investigate the
      role of 11beta-HSD1, we administered a selective 11beta-HSD1 inhibitor in type 1
      and type 2 murine models of diabetes and in cultured cardiomyocytes. Our results
      show that diabetes increases cortisone levels in heart tissues. 11beta-HSD1
      inhibitor decreased cortisone levels and ameliorated all structural and
      functional features of diabetic cardiomyopathy including fibrosis and
      hypertrophy. We also show that high levels of glucose caused cardiomyocyte
      hypertrophy and increased matrix protein deposition in culture. Importantly,
      inhibition of 11beta-HSD1 attenuated these changes. Moreover, we show that 11beta
      HSD1 activation mediates these changes through modulating EGFR phosphorylation
      and activity. Our findings demonstrate that 11beta-HSD1 contributes to the
      development of diabetic cardiomyopathy through activation of glucocorticoid and
      EGFR signaling pathway. These results suggest that inhibition of 11beta-HSD1
      might be a therapeutic strategy for diabetic cardiomyopathy, which is independent
      of its effects on glucose homeostasis.

PMID- 29221205
TI  - Thrombospondin-1 modified bone marrow mesenchymal stem cells (BMSCs) promote
      neurite outgrowth and functional recovery in rats with spinal cord injury.
AB  - Stem cell therapies are currently gaining momentum in the treatment of spinal
      cord injury (SCI). However, unsatisfied intrinsic neurite growth capacity
      constitutes significant obstacles for injured spinal cord repair and ultimately
      results in neurological dysfunction. The present study assessed the efficacy of
      thrombospondin-1 (TSP-1), a neurite outgrowth-promoting molecule, modified bone
      marrow mesenchymal stem cells (BMSCs) on promoting neurite outgrowth in vitro and
      in vivo of Oxygen-Glucose Deprivation (OGD) treated motor neurons and SCI rat
      models. The present results demonstrated that the treatment of BMSCs+TSP-1 could
      promote the neurite length, neuronal survival, and functional recovery after SCI.
      Additionally, TSP-1 could activate transforming growth factor-beta1 (TGF-beta1)
      then induced the smad2 phosphorylation, and expedited the expression of GAP-43 to
      promote neurite outgrowth. The present study for the first time demonstrated that
      BMSCs+TSP-1 could promote neurite outgrowth and functional recovery after SCI
      partly through the TGF-beta1/p-Samd2 pathway. The study provided a novel
      encouraging evidence for the potential treatment of BMSCs modification with TSP-1
      in patients with SCI.

PMID- 29221206
TI  - Single nucleotide polymorphisms rs701848 and rs2735343 in PTEN increases cancer
      risks in an Asian population.
AB  - We performed this meta-analysis to analyze the cancer risk to individuals
      carrying the rs701848 and rs2735343 single nucleotide polymorphisms (SNPs) in the
      phosphatase and tensin homolog (PTEN) gene. We searched the PubMed, EMBASE,
      Cochrane library and the national knowledge infrastructure of China (CNKI)
      databases and identified 18 eligible case-control studies with 5458 cases and
      6003 controls for rs701848 as well as 5490 cases and 6209 controls for rs2735343.
      Our analyses demonstrated that cancer risk was associated with rs701848 in the
      recessive model (CC vs. CT+TT, OR=1.169, 95% CI: 1.061-1.288) and with rs2735343
      in the dominant model (GC+CC vs. GG, OR=0.758, 95% CI: 0.590-0.972). Subgroup
      analysis showed that in Asian subjects, carrying the C allele of rs701848 or GG
      genotype of rs2735343 was associated with increased cancer risk. Moreover, Asian
      subjects carrying the TC/CC genotype or C allele of rs701848 were associated with
      increased risk of esophageal squamous cell cancer. This meta-analysis indicates
      that the PTEN rs701848 (CC) and rs2735343 (GG) polymorphisms are associated with
      increased cancer risk in Asian subjects.

PMID- 29221207
TI  - CHST6 mutation screening and endoplasmatic reticulum stress in macular corneal
      dystrophy.
AB  - Macular corneal dystrophy (MCD) is an autosomal recessive disorder mainly caused
      by gene mutations of carbohydrate sulfotransferase (CHST6) leading to bilateral
      visual impairment. Because the mechanism underlying this degeneration remains
      poorly understood, we investigated molecular alterations and pathways that may be
      involved in MCD in this issue. Different mutation sites were screened by direct
      sequencing of the coding region of CHST6. In addition, we described morphological
      changes in MCD keratocytes by light microscopy and electron microscopy and
      determined the relationship between the development of this disease and the
      occurrence of apoptosis through flow cytometry, cell counting kit-8, colony
      formation assay and other experiments. Western blotting and quantitative real
      time polymerase chain reaction were used to determine if endoplasmic reticulum
      (ER) stress was activated. We found 10 kinds of mutations among these families
      with 3 novel mutations included. The percentage of apoptotic keratocytes
      increased in MCD patients; furthermore, the expression of apoptosis related
      protein B-cell lymphoma-2 (Bcl-2) was down-regulated while Bcl-2 associated X
      protein was upregulated. Finally, ER stress was activated with the upregulation
      of glucose-regulated protein 78 and CCAAT-enhancer-binding protein homologous
      protein. Our clinical and in vitro results suggest that the CHST6 mutation
      associated with MCD is associated with apoptosis, and ER stress is probably
      involved in this apoptosis pathway.

PMID- 29221208
TI  - Higher expression of FOXOs correlates to better prognosis of bladder cancer.
AB  - Background: We aimed to explore the expression of forkhead box class O (FOXO) and
      relations between expressions of FOXOs and clinicopathological characteristics
      and prognosis of bladder cancer. Methods: We enrolled a cohort of 276 patients
      with bladder cancer in our study. Expressions of FOXOs in bladder cancer tissue
      and adjacent tissue were measured by quantitative real-time polymerase chain
      reaction (qRT-PCR) and immunohistochemistry (IHC). Correlations between
      expression of FOXOs and clinicopathological characteristics and prognosis were
      analyzed. The relationship between expression of FOXOs and survival time of
      patients with bladder cancer was analyzed by the Kaplan-Meier survival analysis
      and the Log-rank test; individual variables which may affect the prognosis of
      bladder cancer were detected by the Cox proportional hazard regression model.
      Results: Compared with bladder cancer tissue, a higher expression of FOXOs was
      detected in paracancerous tissue. We found significant associations between
      histological grade and the expressions of FOXOs, clinical stage and the
      expressions of FOXOs, and lymph node metastasis and the expressions of FOXOs (all
      P < 0.05). When used for diagnosing bladder cancer, the mRNA expression of
      FOXO1/3/4 produced cut off values of 1.475, 1.305, and 1.295, respectively,
      exhibiting relatively high specificity and sensitivity. The Kaplan-Meier curves
      indicated that patients with a higher expression of FOXOs tended to have a longer
      overall survival than those with lower expression. The Cox regression analysis
      revealed that lymph node metastasis, high clinical stage, and low expression of
      FOXOs were independent risk factors for bladder cancer prognosis. Conclusion: Our
      results indicate that the expression of FOXOs is closely correlated with
      clinicopathological characteristics and prognosis of bladder cancer.

PMID- 29221210
TI  - The molecular classification of astrocytic tumors.
AB  - Aim: This study will explore the genetic and epigenetic alterations in
      astrocytomas, and identify the critical molecular signatures and signaling
      pathways for prognosis assessment by multiplatform comprehensive analysis.
      Method: We performed integration analyses of incorporating DNA methylation, mRNA
      expression, microRNA expression, and long non-coding RNA (lncRNA) expression in
      33 astrocytic tumor tissues and 9 non-tumor brain tissues. Result: We observed
      that 11,795 DNA methylation sites, 3,627 genes, 136 microRNAs, and 3,334 lncRNAs
      were significantly differential between tumors and non-tumor brain tissues, and
      the filtered signatures through comprehensive analysis were significantly
      enriched in calcium signaling pathway. Furthermore, four signatures involved in
      calcium signaling pathway and age could contribute to predicting the patients'
      overall survival. Additionally, we identified differentially expressed signatures
      between IDH-mutated and IDH wild-type astrocytic tumors, and complement and
      coagulation cascades pathway was the most significant pathway in functional
      enrichment analysis using multiplatform data. The IDH wild-type astrocytomas were
      divided into two subtypes by Cluster of Cluster (CoC) analysis, one of which was
      enriched for astrocytomas overexpressed in chemokine signaling pathway.
      Conclusion: The calcium signaling pathway played a key role in astrocytoma
      tumorigenesis and prognosis. IDH mutation was a vital biomarker, and resulted in
      the change of expression level in complement and coagulation cascades pathway.
      The chemokine signaling pathway could characterize subtypes of IDH wild-type
      astrocytomas.

PMID- 29221209
TI  - Direct HPV E6/Myc interactions induce histone modifications, Pol II
      phosphorylation, and hTERT promoter activation.
AB  - Human Papillomavirus Viruses (HPVs) are associated with the majority of human
      cervical and anal cancers and 10-30% of head and neck squamous carcinomas. E6
      oncoprotein from high risk HPVs interacts with the p53 tumor suppressor protein
      to facilitate its degradation and increases telomerase activity for extending the
      life span of host cells. We published previously that the Myc cellular
      transcription factor associates with the high-risk HPV E6 protein in vivo and
      participates in the transactivation of the hTERT promoter. In the present study,
      we further analyzed the role of E6 and the Myc-Max-Mad network in regulating the
      hTERT promoter. We confirmed that E6 and Myc interact independently and that Max
      can also form a complex with E6. However, the E6/Max complex is observed only in
      the presence of Myc, suggesting that E6 associates with Myc/Max dimers.
      Consistent with the hypothesis that Myc is required for E6 induction of the hTERT
      promoter, Myc antagonists (Mad or Mnt) significantly blocked E6-mediated
      transactivation of the hTERT promoter. Analysis of Myc mutants demonstrated that
      both the transactivation domain and HLH domain of Myc protein were required for
      binding E6 and for the consequent transactivation of the hTERT promoter, by
      either Myc or E6. We also showed that E6 increased phosphorylation of Pol II on
      the hTERT promoter and induced epigenetic histone modifications of the hTERT
      promoter. More important, knockdown of Myc expression dramatically decreased
      engagement of acetyl-histones and Pol II at the hTERT promoter in E6-expressing
      cells. Thus, E6/Myc interaction triggers the transactivation of the hTERT
      promoter by modulating both histone modifications, Pol II phosphorylation and
      promoter engagement, suggesting a novel mechanism for telomerase activation and a
      new target for HPV- associated human cancer.

PMID- 29221211
TI  - The prevalence of polycystic ovary syndrome in reproductive-aged women of
      different ethnicity: a systematic review and meta-analysis.
AB  - The prevalence of PCOS was investigated in many studies in different continents.
      However, there is no established prevalence of PCOS for distinct ethnic groups.
      In the current analysis, we conducted searches in PubMed, The Cochrane Library,
      EMBASE, CINAHL up to Jan. 2017 to identify studies reporting prevalence of PCOS
      in the general female population. Forty-two studies were identified, with 13
      eligible for evidence synthesis. The prevalence among different ethnicity was
      estimated using random effect modelling. Our results suggested the lowest
      prevalence in Chinese women(2003 Rotterdam criterion: 5.6% 95% interval: 4.4
      7.3%), and then in an ascending order for Caucasians (1990 NIH criterion: 5.5%
      95% interval: 4.8-6.3%), Middle Eastern (1990 NIH 6.1% 95% interval: 5.3-7.1%;
      2003 Rotterdam 16.0% 95% interval: 13.8-18.6%; 2006 AES 12.6% 95% interval: 11.3
      14.2%), and Black women (1990 NIH: 6.1% 95% interval: 5.3-7.1%).There is
      variation in prevalence of PCOS under different diagnostic criteria and across
      ethnic groups. This emphasises the need for ethnicity-specific guidelines for
      PCOS to prevent under- or over-diagnosis of the condition given that under
      diagnosis may lead to rapid conversion of metabolic disorders for patients
      whereas over-diagnosis may exert negative psychological effects on patients which
      worsens the major symptoms of PCOS.

PMID- 29221212
TI  - Prognostic and clinicopathological significance of MUC expression in head and
      neck cancer: a systematic review and meta-analysis.
AB  - The prognostic value of mucins expression in patients with head and neck cancer
      (HNC) remains controversial. To address this, a meta-analysis was performed to
      systematically evaluate prognostic significance of mucins expression in HNC.
      Electronic and manual searches were performed and a total of 20 studies including
      2046 patients were selected for the final analysis. Increased mucins expression
      was associated with unfavorable overall survival in HNC patients (HR=1.83, 95%
      CI: 1.43-2.33, p=0.000). Mucins overexpression was also in correlation with more
      advanced TNM stage (RR=0.84, 95% CI: 0.73-0.97, p=0.017), higher risk of lymph
      node metastasis (RR=0.69, 95% CI: 0.57-0.84, p=0.000) and deeper invasion
      (RR=0.58, 95% CI: 0.44-0.76, p=0.000). These results suggested that elevated
      mucins expression was significantly associated with worse prognosis and more
      detrimental clinicopathological outcomes, revealing the promising potential of
      mucins as biomarkers for HNC management.

PMID- 29221213
TI  - The prognostic significance of high/positive expression of cyclin B1 in patients
      with three common digestive cancers: a systematic review and meta-analysis.
AB  - Recently, several studies have reported that the expression of cyclin B1 may be
      associated with the prognosis of cancer. Nevertheless, their conclusions were
      still controversial. The present was designed to analyze and evaluate the
      prognostic role of cyclin B1 expression in patients with digestive cancer.
      PubMed, Embase, Cochrane Library and Web of Science were searched to January,
      2017. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were estimated.
      For the pooled OR estimates of OS, we performed subgroup analysis. Besides,
      sensitivity analysis was performed to examine the stability of the combined
      results. All statistical analyses were performed using standard statistical
      procedures provided in RevMan 5.2. A total of 12 studies (N = 2080 participants)
      were included for this meta-analysis. The positive/high expression of cyclin B1
      had an obvious association with both 3-year overall survival (OR 0.21, 95% CI
      0.12-0.37; P < 0.00001) and 5-year overall survival (OR 0.20, 95% CI 0.12-0.34; P
      < 0.00001) in esophageal cancer, and 5-year overall survival of colorectal cancer
      (OR 2.01, 95% CI 1.32-3.08; P = 0.001). This meta-analysis indicated that
      positive/high expression of cyclin B1 may have a close association with worse
      survival in patients with esophageal cancer, but better prognosis in patients
      with colorectal cancer.

PMID- 29221215
TI  - DNMT1 overexpression predicting gastric carcinogenesis, subsequent progression
      and prognosis: a meta and bioinformatic analysis.
AB  - DNMT1 is important in maintaining DNA methylation, and participates in the
      oncogenesis via up- or down-regulation leading to hyper-methylation or hypo
      methylation. In the meta and bioinformatic analysis, we found that DNMT1
      expression was higher in gastric cancer, compared with normal (p < 0.00001), para
      cancerous (p = 0.0004) and dysplasia (p < 0.00001) tissues. DNMT1 up-regulation
      was associated with gender (OR = 2.27, p = 0.006), differentiation (OR = 0.21, p
      = 0.01) and TNM stage (OR = 0.31, p = 0.0005). Through TCGA database, DNMT1
      overexpression increased gastric cancer risk, but unrelated with
      clinicopathological parameters and prognosis. Kaplan-Meier plotter showed, an
      increasing expression of DNMT1 was positive for overall survival rates of
      patients with stage III and IV (P = 0.044; P = 0.047), N2 and N1-3 phases of
      lymph node metastasis (P = 0.023; P = 0.032), as well as those with or without
      distant metastasis (P = 0.0052; P = 0.021). For DNMT1 negative patients, the
      progression-free survival rates was better in patients with Her2+ or Her2- than
      positive ones (P = 0.00015; P = 0.031). Besides, surgery alone was effective for
      the overall survival rates in patients with DNMT1 high expression (P = 0.035),
      while 5-Fu was useful for those with low expression (P < 0.05). In conclusion,
      these findings provided evidence that DNMT1 expression might be employed as a
      potential marker to indicate gastric carcinogenesis and subsequent progression,
      even prognosis.

PMID- 29221214
TI  - Prognostic value of MICA/B in cancers: a systematic review and meta-analysis.
AB  - Purpose: MHC class I chain related-proteins A (MICA) and B (MICB) are natural
      killer group 2D ligands that mediate tumor surveillance. Several studies have
      suggested that MICA/B levels predict clinical outcomes in patients with cancer;
      however, this remains contentious. Here, we present a systematic review and meta
      analysis of available studies of the prognostic value of MICA/B in cancer.
      Materials and Methods: We searched PubMed, Embase, Clinicaltrials.gov, and
      Cochrane Library to identify studies published from inception to July 2017 that
      assessed MICA/B in patients with cancer. The hazard ratio (HR) and 95% confidence
      interval (CI) of MICA/B were extracted for overall survival (OS) analysis.
      Results: A total of 19 studies comprising 2,588 patients with 10 different types
      of cancer were included in the study. Low sMICA/B levels were found associated
      with significantly longer OS (HR = 1.65, 95% CI [1.42-1.92], P < 0.00001).
      Patients with cancers of digestive system that exhibited high MICA/B expression
      had significantly longer OS in (HR = 0.56, 95% CI [0.39-0.80], P = 0.002)
      compared with those with lower MICA/B expression (I2 = 35%, P = 0.18).
      Conclusions: Serum soluble MICA/B represents a potential prognostic marker in
      various human cancers. High cell-surface MICA/B expression in cancers of the
      digestive system was found associated with increased survival.

PMID- 29221216
TI  - Probiotics in 14-day triple therapy for Asian pediatric patients with
      Helicobacter pylori infection: a network meta-analysis.
AB  - : Although 14-day triple therapy has been widely administrated for eradicating
      Helicobacter pylori (H. pylori) in Asia, its antibiotic-associated side effects
      restrict the effectivity of eradication therapy in pediatric patients. Therefore,
      a network meta-analysis (NMA) was conducted to compare the efficacy and safety of
      probiotics supplemented in 14-day triple therapy in Asian pediatric patients.
      Materials and Methods: Randomized controlled trials (RCTs) were retrieved
      comprehensively in electronic databases (such as PubMed, Cochrane library,
      Embase, CNKI, Wan fang database, VIP database and CBM) until April 2017.
      Additional references were obtained from reviewed articles. NMA was performed
      using a random-effects model under a frequentist framework. Results: Seventeen
      RCTs were included. NMA indicated that Bifidobacterium infantis+Clostridium
      butyricum was most beneficial for H. pylori eradication rates (P-score = 0.82)
      and Bacillus mesentericus+Clostridium butyricum+Streptococcus faecalis for total
      side effects (P-score = 0.77). Taken together, Bacillus mesentericus+Clostridium
      butyricum+Streptococcus faecalis was the best one to supplement in 14-day triple
      therapy due to its efficacy (P-score = 0.72) and safety (P-score = 0.77).
      Additionally, pairwise meta-analysis indicated that probiotics supplemented 14
      day triple therapy significantly increased H. pylori eradication rates (RR: 1.16,
      95%CI: 1.07-1.26) and reduced the incidence of total side effects (RR: 0.40,
      95%CI: 0.34-0.48) compared with placebo. Conclusions: Bacillus
      mesentericus+Clostridium butyricum+Streptococcus faecalis is the optimal
      probiotic regime of reducing total side effects and improving eradication rates
      when supplemented 14-day triple therapy. Further direct evidence is needed to
      warrant it.

PMID- 29221217
TI  - The association between human papillomavirus infection and lung cancer: a system
      review and meta-analysis.
AB  - To estimate the global attributable fraction of human papillomavirus (HPV) in
      lung cancer, we provided updated information through a system review and meta
      analysis. We did a literature search on PubMed, Ovid and Web of Science to
      identify case-control studies and cohort studies that detected HPV in lung
      carcinomas. We included studies that tested 30 or more cases and were published
      before Feb 28, 2017. We collected information about gender, smoking status, HPV
      detection methods, HPV types, materials and clinical features. If it was not
      possible to abstract the required information directly from the papers, we
      contacted the authors. A meta-analysis was performed to calculate the pooled
      effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup
      analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0
      software. 36 case-control studies, contributing data for 6,980 cases of lung
      cancer and 7,474 controls from 17 countries and one cohort study with 24,162
      exposed and 1,026,986 unexposed from China were included. HPV infection was
      associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60-5.08),
      calculated with the random-effects model. Pooled OR for allogeneic case-control
      studies, self-matched case-control studies and nested case-control studies were
      6.71 (95% CI: 4.07-11.07), 2.59 (95% CI: 1.43-4.69) and 0.92 (95% CI: 0.63-1.36),
      respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07
      4.76) and 2.25 (95% CI: 1.49-3.40), respectively. We also found that HPV
      infection may be associated with squamous cell carcinoma, adenocarcinoma and
      small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and
      HPV 18 infection, significantly increase the risk of lung cancer. Future research
      needs to focus attention toward whether an HPV vaccine can effectively reduce the
      incidence of lung cancer.

PMID- 29221218
TI  - TERT rs2736098 (Ex2-659G>A) polymorphism and cancer susceptibility: evidence from
      a comprehensive meta-analysis.
AB  - : Increasing researches have been performed regarding the relationship between
      TERT rs2736098 and cancer risk, but no consensus has been reached about the
      relationship. Here, we conducted this updated meta-analysis, aiming to
      comprehensively evaluate the role of TERT rs2736098 in cancer risk. We
      systematically searched potential relevant articles through PubMed, EMBASE, CNKI,
      and WanFang database before August 2017. A total of 33 studies with 18685 cases
      and 23820 controls were finally included in the current meta-analysis. We then
      adopted odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the
      contributions of TERT rs2736098 to cancer risk. We found that the TERT rs2736098
      polymorphism was associated with risk of cancer in overall analysis (AA vs. GG:
      OR = 1.26, 95% CI = 1.09-1.47; AA vs. AG/GG: OR = 1.22, 95% CI = 1.09-1.36; AA/AG
      vs. GG: OR = 1.13, 95% CI = 1.02-1.24; A vs. G: OR = 1.11, 95% CI = 1.04-1.20).
      Furthermore, in analysis stratified by cancer type, ethnicity, control source,
      quality score, and Hardy-Weinberg equilibrium (HWE) in controls, we found
      increased risk of cancer among lung cancer, bladder cancer, breast cancer,
      colorectal cancer, other cancers, Asians, hospital-based subgroup, score > 9
      group, as well as controls agreement with HWE group. Despite some limitations,
      the current meta-analysis represented the largest and the most comprehensive
      investigations, with the strongest conclusion than ever before. To further
      explicit the association between TERT rs2736098 and cancer risk, more well-design
      case-control studies with larger sample size are warranted in the future.

PMID- 29221219
TI  - The paradox of the first cycle of chemotherapy-transient improvement of
      contractility and diastolic function after the first cycle of anthracycline-based
      chemotherapy: a prospective clinical trial.
AB  - Aims: Breast cancer is the most common cancer among women, and anthracyclines are
      the most commonly administered drugs for these patients. Cardiotoxicity is one of
      the complications, which limits the success of this therapy. Very few studies
      have evaluated anthracycline toxicities within the first few hours after the
      first infusion, and the majority of published studies were performed in animal
      models. The present study aimed to evaluate changes in echocardiographic
      parameters in women with breast cancer 24 hours after receiving the first dose of
      an anthracycline. Materials and Methods and Results: The present study included
      75 chemotherapy-naive female patients without heart failure, who were diagnosed
      with breast cancer and were scheduled to undergo anthracycline-based chemotherapy
      (epirubicin and doxorubicin). During their visits to the Heart Center, the
      patients underwent detail echocardiographic examination, including assessment of
      systolic and diastolic function and longitudinal strain. There were no
      differences in baseline echocardiographic parameters between patients with and
      those without cardiotoxicity. Cardiotoxicity was observed during follow-up in 14
      patients (18.7%). Improvements in left ventricular ejection fraction and global
      longitudinal strain were observed at 24 hours after administration of the
      cytotoxic agent in the subgroup of patients without further cardiotoxicity. The
      changes were transient and the assessment of left ventricular ejection fraction
      after completion of chemotherapy revealed similar values to those before the
      treatment. Conclusions: The findings of our study suggest that transient
      improvement in contractility and systolic and diastolic function might occur 24
      hours after anthracycline administration, especially in patients who do not
      develop cardiotoxicity.

PMID- 29221220
TI  - Significant benefit of Nivolumab treating PD-L1 positive metastatic pulmonary
      carcinosarcoma: a case report and literature review.
AB  - Immunotherapy has recently become a new focus for the treatment of malignant
      tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted
      therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell
      death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its
      ligand (PD-L1), restoring the immune response of T cells, and enhancing the
      recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an
      uncommon but highly aggressive tumor type with a poor prognosis. We described a
      case of pulmonary carcinosarcoma, with the positive expression of PD-L1, obtained
      a significant benefit from Nivolumab treatment in a 64-year-old Chinese man,
      which give us a clue that patients with pulmonary carcinosarcoma may benefit
      fromanti-PD-1 immunotherapy.

PMID- 29221221
TI  - Aortic valve replacement after bypass surgery: surgical (SAVR) or transcatheter
      (TAVR).

PMID- 29221222
TI  - Polymyxin B hemoperfusion in septic shock: nothing overmuch (Meden Agan)!

PMID- 29221223
TI  - Three-dimensional printing in cardiovascular surgery: logical next step after
      three-dimensional imaging.

PMID- 29221224
TI  - Acute diseases, emergency admissions and mortality during weekends: should we be
      worried?

PMID- 29221226
TI  - Unraveling the mystery of dreams.

PMID- 29221225
TI  - Mediastinal lymph node dissection in surgical treatment for early stage non-small
      cell lung cancer: lobe-specific or systematic?

PMID- 29221227
TI  - PET-guided treatment algorithms in oesophageal cancer: the promise of the near
      future!

PMID- 29221228
TI  - Transcription factor SPZ1 may promote TWIST-mediated epithelial-mesenchymal
      transition in thoracic malignancies.

PMID- 29221229
TI  - Tracking occult pN2 disease after mediastinal dissection in early stage lung
      cancer.

PMID- 29221230
TI  - Neoadjuvant strategy for stage IIIA-N2 non-small cell lung cancer: chemoradiation
      or chemotherapy alone?

PMID- 29221231
TI  - Primary prevention implantable cardioverter defibrillator in patients with
      reduced ejection fraction: for ischemic or non-ischemic cardiomyopathy or both?

PMID- 29221232
TI  - Ischemic postconditioning during primary percutaneous coronary interventions-not
      ready for prime time.

PMID- 29221233
TI  - Taking the measure of lung adenocarcinoma: towards a quantitative approach to
      tumor spread through air spaces (STAS).

PMID- 29221234
TI  - Editorial on "Neurologic injury in adults supported with veno-venous
      extracorporeal membrane oxygenation for respiratory failure: findings from the
      Extracorporeal Life Support Organization database".

PMID- 29221235
TI  - Triaging patients with left main disease after the EXCEL and NOBLE trials: the
      everlasting saga of coronary artery bypass grafting and percutaneous coronary
      intervention.

PMID- 29221236
TI  - Checkpoint inhibitors in metastatic epidermal growth factor receptor-mutated non
      small cell lung cancer patients: where we treating the wrong cancer?

PMID- 29221237
TI  - Neurologic complications during V-V extracorporeal membrane oxygenation: still
      counting....

PMID- 29221238
TI  - Protecting lungs during spontaneous breathing: what can we do?

PMID- 29221239
TI  - Inflammatory status and prognosis of locally advanced non-small cell lung cancer.

PMID- 29221240
TI  - Composite metrics in response assessment-new hope in oesophageal cancer?

PMID- 29221241
TI  - ATHOS-3 and the knights of the round table-the search for the holy grail of
      vasopressors.

PMID- 29221242
TI  - Practical clinical applications of 3-D printing in cardiovascular surgery.

PMID- 29221243
TI  - Transcatheter aortic valve implantation with the repositionable and fully
      retrievable Lotus Valve SystemTM.

PMID- 29221244
TI  - The Lotus dilemma-respond to paravalvular leakage, but not answering pacemaker
      implantations?

PMID- 29221245
TI  - In sepsis, beyond adherence, timeliness matters.

PMID- 29221246
TI  - Moving more potent and less toxic options to the frontline in the management of
      advanced lung cancer.

PMID- 29221247
TI  - Should cT2 esophageal cancer get neoadjuvant treatment before surgery?

PMID- 29221248
TI  - The search for long-term outcome predictors.

PMID- 29221249
TI  - Antimicrobial prophylaxis is critical for preventing surgical site infection.

PMID- 29221250
TI  - Should cT2N0M0 be managed as a localized or locally advanced esophageal
      carcinoma?

PMID- 29221251
TI  - Unless I see, I will not believe.

PMID- 29221252
TI  - Pure ground-glass nodules: are they really indolent?

PMID- 29221253
TI  - Twice-daily chemoradiotherapy must still be the choice for patients with limited
      stage small-cell lung cancer.

PMID- 29221254
TI  - Recent studies move closer to answering questions about sequential therapy for
      anaplastic lymphoma kinase-rearranged non-small cell lung cancer.

PMID- 29221255
TI  - Anticoagulating atrial fibrillation patients: is there a kidney-friendly choice?

PMID- 29221256
TI  - Exercise Doppler echocardiography for the diagnosis of pulmonary hypertension:
      renewed interest and evolving roles.

PMID- 29221257
TI  - Adenocarcinoma in pure ground glass nodules: histological evidence of invasion
      and open debate on optimal management.

PMID- 29221258
TI  - Neoadjuvant DCF vs. ACF for resectable oesophageal squamous cell carcinoma.

PMID- 29221259
TI  - Recent advances in video-assisted transthoracic tracheal resection followed by
      reconstruction under non-intubated anesthesia with spontaneous breathing.

PMID- 29221260
TI  - Thoracoscopic tracheal resection and reconstruction: video-assisted thoracoscopic
      surgery as a "tool" toward minimally invasive surgery.

PMID- 29221261
TI  - Clinical analysis of acute myocardial infarction caused by coronary embolism.
AB  - Background: This study aims to investigate the clinical and angiographic features
      in patients with acute myocardial infarction (AMI) induced by coronary artery
      embolism. Methods: Clinical data of five patients with AMI induced by coronary
      artery embolism were analyzed retrospectively. Results: One patient had left
      atrial myxoma, one patient had non-valvular atrial fibrillation, and three
      patients had rheumatic heart disease. Furthermore, one patient had mitral
      mechanical valve prostheses, two patients had atrial fibrillation. Coronary
      angiography showed the absence of significant atherosclerostic lesions in the
      coronary arteries except infarct related artery in five patients. Angiography
      suggested the presence of IRA occlusion caused by embolism. Conclusions: The
      status for AMI due to coronary artery embolism usually expresses embolic material
      originating from the left heart chambers. Rheumatic heart disease and atrial
      fibrillation are the common reasons for coronary artery embolism. Coronary artery
      occlusion is the common performance in the results of primary coronary artery
      angiography. Sometimes it expresses visible signs of embolism.

PMID- 29221262
TI  - Differences in airway remodeling and airway inflammation among moderate-severe
      asthma clinical phenotypes.
AB  - Background: To identify asthma clinical phenotypes using cluster analysis and
      improve our understanding of heterogeneity in asthma. Methods: Clustering
      approaches were applied to 203 patients who were diagnosed with asthma in XinHua
      Hospital (January 2012 to December 2015). One hundred and twenty patients
      underwent multi-slice spiral computed tomography (MSCT) examination and 30
      underwent bronchial mucosal biopsy for evaluation of airway remodeling and airway
      inflammation among the phenotypes. Results: Four groups were identified. Patients
      in cluster 1 (n=52) had early onset atopic asthma and patients in cluster 2
      (n=65) had small airway obstruction and atopic asthma. Cluster 3 (n=52) was a
      unique group of patients with late-onset and non-atopic asthma. Patients in
      cluster 4 (n=34) had severe airflow obstruction and obvious airway remodeling as
      observed on MSCT (P<0.05). According to the immunohistochemistry of IL-5 and IL
      17 (P<0.05), the results of clusters 1 and 2 may be attributable to the Th2
      immune response, whereas those of clusters 3 and 4 to the Th17 immune response.
      Conclusions: Four distinct clinical phenotypes of asthma were identified by
      cluster analysis. The results of the MSCT and pathological examinations may
      suggest specific pathogeneses among the phenotypes.

PMID- 29221263
TI  - A prospective randomized trial comparing homologous and autologous fibrin
      sealants for the control of alveolar air leak.
AB  - Background: Postoperative air leak is a common complication seen after pulmonary
      resection. It is a significant reason of morbidity and also leads to greater
      hospital cost owing to prolonged length of stay. The purpose of this study is to
      compare homologous sealant with autologous one to prevent air leak following
      pulmonary resection. Methods: A total of 57 patients aged between 20 and 79 (mean
      age: 54.36) who underwent pulmonary resection other than pneumonectomy (lobar or
      sublobar resections) were analyzed. There were 47 males (83%) and 10 females
      (17%). Patients who intraoperatively had air leaks were randomized to receive
      homologous (Tisseel; n=28) or autologous (Vivostat; n=29) fibrin sealant.
      Differences among groups in terms of air leak, prolonged air leak, hospital stay,
      amount of air leak were analyzed. Results: Indications for surgery were primary
      lung cancer in 42 patients (71.9%), secondary malignancy in 5 patients (8.8%),
      and benign disease in 10 patients (17.5%). Lobectomy was performed in 40 patients
      (70.2%), whereas 17 patients (29.8%) had wedge resection. Thirteen (46.4%)
      patients developed complications in patients receiving homologous sealant while
      11 (38.0%) patients had complication in autologous sealant group (P=0.711).
      Median duration of air leak was 3 days in two groups. Time to intercostal drain
      removal was 3.39 and 3.38 days in homologous and autologous sealant group
      respectively (P=0.978). Mean hospital stay was 5.5 days in patients receiving
      homologous sealant whereas it was 5.0 days in patients who had autologous agent
      (P=0.140). There were no significant differences between groups in terms of
      measured maximum air leak (P=0.823) and mean air leak (P=0.186). There was no
      significant difference in the incidence of complications between two groups
      (P=0.711). Conclusions: Autologous and heterologous fibrin sealants are safe and
      acts similarly in terms of air leak and hospital stay in patients who had
      resectional surgery.

PMID- 29221264
TI  - Continuation of gefitinib plus chemotherapy prolongs progression-free survival in
      advanced non-small cell lung cancer patients who get acquired resistance to
      gefitinib without T790M mutations.
AB  - Background: Aimed to identify the benefit population from continuation of
      epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), this
      study investigated the efficacy of continuation of EGFR-TKIs plus chemotherapy
      beyond the response evaluation criteria in solid tumors-progressive disease
      (RECIST-PD) according to different progression modes and T790M mutational status.
      Methods: From November 2009 to July 2015, 630 patients with advanced non-small
      cell lung cancer (NSCLC) receiving gefitinib as initial EGFR-TKI treatment were
      screened in Shanghai Pulmonary Hospital. A total of 170 patients with documented
      gradual or dramatic progression after gefitinib treatment who received
      chemotherapy alone or in combination with gefitinib were included. Post-RECIST-PD
      progression-free survival (PPFS) between continuation of gefitinib plus
      chemotherapy and chemotherapy alone was assessed. Results: The incidence of T790M
      mutation was 42.9% (63/147) in patients who got acquired resistance in this
      study. Median PPFS was 4.0 months [95% confidence interval (CI), 3.1-4.9 months]
      in the chemotherapy group and 5.0 months (95% CI, 3.6-6.4 months) in the
      combination group with a borderline statistical significance (P=0.071).
      Continuation of gefitinib plus chemotherapy resulted in a significant improvement
      in PPFS compared with chemotherapy alone in patients with EGFRT790M-negative
      tumors [median PPFS: 6.6 vs. 3.5 months, hazard ratio (HR) 0.50, 95% CI, 0.29
      0.88; P=0.011], especially in pemetrexed-based chemotherapy (HR 0.45, 95% CI,
      0.24-0.86; P=0.011). PPFS was similar in patients with EGFRT790M-positive tumors
      (median PPFS: 5.0 vs. 5.5 months, HR 0.80, 95% CI, 0.40-1.61; P=0.520) or
      EGFRT790M-unknown tumors (median PPFS: 2.0 vs. 3.0 months, HR 1.40, 95% CI, 0.69
      2.81; P=0.323). Conclusions: Our study showed that continuous gefitinib plus
      chemotherapy, especially pemetrexed-based therapy, significantly improved PPFS in
      patients with EGFRT790M-negative tumors as compared with chemotherapy alone,
      suggesting that this subtype of patients may derive clinical benefit from
      continuation of gefitinib treatment beyond progression.

PMID- 29221265
TI  - Outcomes of surgical treatment in 115 patients with primary cardiac tumours: a 15
      year experience at a single institution.
AB  - Background: Primary cardiac tumours are rare, and few studies have examined large
      samples. The aim of this study was to review a single institution's 15 years of
      experience with primary cardiac tumours. Methods: We conducted a retrospective
      analysis of 119 consecutive patients admitted to the Nanjing Drum Tower Hospital
      from April 2002 to January 2017. Five patients declined surgery due to illness or
      for financial reasons, and one patient underwent a second operation due to tumour
      recurrence 10 years after the first operation. In total, 115 patients underwent
      surgery. The surgeons used median sternotomy and a right atrial approach to
      complete the gross total resection. The patients were separated into three groups
      according to their tumour pathology (myxomas, other benign tumours, or malignant
      tumours). A total of 84 patients were followed up for an average of 34.8+/-31.2
      months (range 2-141 months). Results: The sites of the cardiac tumours included
      the left atrium (n=93, 80.1%), right atrium (n=14, 14.0%), left ventricle (n=2,
      1.7%), valves (n=7, 6.0%), and other sites (n=1, 0.8%). According to the
      postoperative pathology, 99 (86.0%) tumours were classified as myxomas, 8 (7.0%)
      were other types of benign tumours, and 8 (7.0%) were malignant tumours. Patients
      with malignant tumours had a longer surgical time (P=0.035) and postoperative
      hospitalization time (P=0.009). Patients with myxoma tumours exhibited better 5
      year survival than patients with malignant tumours (95.7% vs. 57.1%, P<0.001).
      Conclusions: In the Chinese population, the incidence of primary cardiac tumours
      is mainly attributable to myxomas. Gross total resection is a safe and effective
      treatment for both benign and malignant tumours. Long-term survival is
      satisfactory for benign tumours but low for malignant tumours, and a risk of
      recurrence exists. Postoperative chemotherapy or radiotherapy may be needed to
      achieve better outcomes.

PMID- 29221266
TI  - Prognostic impact of controlling nutritional status score in resected lung
      squamous cell carcinoma.
AB  - Background: The preoperative immune-nutritional status has been shown to predict
      the postoperative prognosis in various types of cancer; however, the prognostic
      significance of the controlling nutritional status (CONUT) score in resected lung
      squamous cell carcinoma (SCC) has yet to be elucidated. Methods: A total of 108
      patients with resected lung SCC were analyzed for their clinicopathological
      factors, including the CONUT score, which can be calculated from the serum
      albumin, total cholesterol, and total peripheral lymphocyte count. The patients
      were divided into two groups: CONUT low (0 or 1) or high (>=2). Results: Among
      108 patients, 76 (70.4%) were CONUT low, while 32 (29.6%) were CONUT high. No
      significant association between the CONUT score and the clinicopathological
      factors was found. Patients with CONUT high exhibited significantly shorter
      disease-free and overall survivals (DFS and OS) than those with CONUT low
      (P=0.016 and P=0.006, respectively). Multivariate analyses showed that the CONUT
      score [hazard ratio (HR): 1.902, 95% confidence interval (CI): 1.045-3.373,
      P=0.036], age (HR: 2.286, 95% CI: 1.246-4.304, P=0.007), pathological stage (HR:
      2.527, 95% CI: 1.391-4.644, P=0.002), and lymphatic invasion (HR: 2.321, 95% CI:
      1.110-4.493, P=0.027) were independent prognostic factors for the DFS.
      Furthermore, in a multivariate analysis, the CONUT score (HR: 1.909, 95% CI:
      0.902-3.860, P=0.081), age (HR: 2.455, 95% CI: 1.208-5.178, P=0.013),
      pathological stage (HR: 2.488, 95% CI: 1.201-5.306, P=0.014), and lymphatic
      invasion (HR: 3.409, 95% CI: 1.532-7.240, P=0.004) were shown to be independent
      prognostic factors for the OS. Conclusions: The current study showed that the
      CONUT score was an independent prognostic factor for the DFS and OS in patients
      with resected lung SCC.

PMID- 29221267
TI  - The acceptance of illness, the intensity of pain and the quality of life in
      patients with lung cancer.
AB  - Background: Lung cancer is the major cause of cancer related deaths worldwide.
      The overall 5-year survival rate is very low and accounts for only 15%. Poor
      quality of life is considered a prognostic factor for shorter survival in lung
      cancer patients. The aim of the study was to examine the relationships between
      pain, the acceptance of illness and quality of life in patients with lung cancer.
      Methods: The study included 155 patients with lung cancer with mean age of 62.23
      [standard deviation (SD)=9.86] years. We used the Acceptance of Illness Scale
      (AIS) and the Visual Analog Scale (VAS) for pain, and the Short Form Health
      Survey (SF-8) for the assessment of quality of life. For statistical analysis,
      Spearman's rank correlation coefficient and linear regression method were used.
      Results: Mean score of the acceptance of illness was 27.1 (SD=9.2). Mean score of
      the pain severity as measured by the VAS was 4.07 (SD=1.83). The acceptance of
      illness was significantly positively correlated with all the domains of quality
      of life. Both the AIS and the VAS were independent determinants of physical and
      mental components of quality of life. Age and World Health Organization (WHO)
      performance status were additional predictors of physical component of quality of
      life. Conclusions: The knowledge about the acceptance of illness, consequences of
      the decreased acceptance of illness, and factors affecting its level in patients
      with lung cancer is still insufficient. Relationships among acceptance of
      illness, quality of life, and pain should be further investigated.

PMID- 29221268
TI  - The introduction of electromagnetic navigation bronchoscopy for the diagnosis of
      small pulmonary peripheral lesions in an Asian population.
AB  - Background: Electromagnetic navigation bronchoscopy (ENB) is emerging as a useful
      new technique for diagnosing small pulmonary peripheral lesions (SPPLs). However,
      the accuracy and efficiency of ENB have not been investigated in Asian
      populations where the differential diagnoses for SPPLs may be different. To
      analyze this question, this study included patients who received diagnostic ENB
      followed by surgery for the excision of SPPLs. Methods: Consecutive patients
      referred to the Department of Thoracic Surgery, Shanghai Pulmonary Hospital
      (Tongji University), between May 2014 and April 2015 were recruited. ENB was used
      to obtain biopsy tissue and make a diagnosis, which was then confirmed by
      histopathological examination. Results: The ENB was performed on 84 SPPLs of 78
      patients in the study, with four patients having more than one SPPL. It
      successfully reached and biopsied 81 lesions. The average ENB navigation time was
      10.8 minutes (range, 0.5-52 minutes). No mortality occurred, with only two
      complications (one bleeding and one pneumothorax). The mean diameter of the
      biopsied SPPLs was 19.0 mm (range, 5.0-30.0 mm). The distance from the sensor
      probe to the focus was 8.0 mm (range, 1-16 mm). ENB diagnosis had identical
      results with histopathology examination in 81 lesions (37 lung cancer and 41 non
      lung cancer). The sensitivity of ENB was 92.9% (78 out of 84 lesions) in this
      study. Conclusions: These data suggested that ENB was an accurate and efficient
      procedure to sample and diagnose SPPLs in the Asian population. It appeared that
      ENB had a high percentage of successful results in both navigating and aiding in
      the diagnosis of SPPLs in the Asian population.

PMID- 29221269
TI  - Cluster analysis of acute ascending aortic dissection provides novel insight into
      mechanisms of distal progression.
AB  - Background: Whether primary tear size impacts extent of type A dissection is
      unclear. Using statistical groupings based on dissection morphology, we examined
      its relationship to primary tear area. Methods: We retrospectively reviewed 108
      patients who underwent acute ascending dissection repair from 2000-2016.
      Dissection morphology was characterized using 3-dimensional (3D) reconstructions
      of computed tomography (CT) scan images. Two-step cluster analysis was performed
      to group the dissections by examining the true lumen area as a fraction of the
      total aortic area at various levels. Results: Cluster analysis defined two
      distinct categories. This first grouping corresponds to DeBakey type I (n=71,
      65.7%) with a dissection extending from the ascending aorta to the aortic
      bifurcation. The second grouping conforms more closely to DeBakey type II
      dissection (n=37, 34.3%). It differs however from the classic type II definition
      as the dissection may extend up to the distal arch from the ascending aorta.
      Compared to type I, this "extended" DeBakey type II had no malperfusion (P<0.05),
      a larger primary tear area (6.6 vs. 3.7 cm2, P=0.009), and a greater burden of
      atherosclerotic coronary artery disease (P<0.05). A smaller aortic valve annulus
      (P=0.025) and a smaller root false lumen area (P=0.017) may explain less aortic
      valve insufficiency (P<0.05) in extended type II dissections. No differences in
      complications or survival were seen. Conclusions: In this series, limited distal
      extension of DeBakey type II dissections appears to be related to a larger
      primary tear area and greater atherosclerotic disease burden. It is also
      associated with less malperfusion and aortic valve insufficiency.

PMID- 29221270
TI  - Analysis of the clinical differentiation of pulmonary sclerosing pneumocytoma and
      lung cancer.
AB  - Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign lung tumor.
      This study investigated the diagnostic experience of PSP and lung cancer.
      Methods: This study is a retrospective study. We observed the locations of lung
      lesions, imaging form and clinical symptoms, and recorded the surgical
      complications through comparing patients with PSP and lung cancer. Results: From
      December 2012 to February 2017, 187 PSP cases and 197 lung cancer cases were
      collected. PSP was commonly found in women (88.2%), often occurred in the left
      lower lobe (32.6%), and was associated with a lesion size of 10-20 mm (48.7%).
      PSP patients presented with cough, sputum, chest pain, and most patients had a
      single lesion, which could showed no clear boundary. Most PSP patients exhibited
      no enlargement of mediastinal lymph nodes, had no involvement of the blood
      vessels, and had low computed tomography (CT) values (low Hounsfield units). Lung
      cancers were more commonly found in men (69.0%), with the lesions scattered
      throughout all lobes of the lung. Cases with a tumor size >30 mm accounted for
      76.2% of patients. Lung cancer patients also presented systemic symptoms, and the
      tumors were found to have unclear boundaries. Moreover, patients presented with
      enlarged mediastinal lymph nodes, high CT values, and heterogeneous internal
      tumor texture. Conclusions: This study showed that PSP was rare and difficult to
      differentiate from lung cancer. PSP was often found in 40-70-year-old non-smoking
      women and most patients presented with cough and sputum. Patients often had a
      single lesion, which was commonly located in the left lower lobe and could have
      unclear boundaries. The majority of patients exhibited no enlargement of
      mediastinal lymph nodes and had low CT values. Therefore, our results can provide
      some basis for the differential diagnosis of PSP and lung cancer.

PMID- 29221271
TI  - Minimally invasive esophagectomy is a safe surgical treatment for locally
      advanced pathologic T3 esophageal squamous cell carcinoma.
AB  - Background: Previous studies have shown that minimally invasive esophagectomy
      (MIE) is safe and feasible. However, several of these studies had selection bias
      because they included more patients with early-stage cancer, and no study has
      compared the outcomes of locally advanced pathologic T3 (pT3) esophageal
      carcinoma between MIE and open surgery. Methods: This retrospective analysis
      included 229 patients with stage pT3 esophageal squamous cell carcinoma (ESCC)
      who underwent esophagectomy from January 2013 to June 2015. The outcomes included
      operative outcomes, postoperative complications, recurrence, and mid-term
      survival. Results: Sixty-six patients underwent MIE and 163 patients underwent
      open surgery. No significant difference was noted in blood loss or resection
      completeness (R0) between the two groups. The operative duration was longer in
      the MIE than open surgery group (266.5+/-52.5 vs. 218.1+/-47.4, P<0.01), and the
      number of lymph nodes dissected was higher in the MIE than open surgery group
      (15.2+/-5.3 vs. 12.9+/-7.3, P=0.01). There was no significant difference in the
      length of stay or 30-day mortality rate between the two groups, but the intensive
      care unit stay was shorter in the MIE group (3 vs. 4, P=0.01). No difference in
      complications or recurrence was noted between the two groups. The 2-year overall
      survival (OS) rate was 72.8% for MIE and 69.4% for open surgery, and the 2-year
      disease-free survival (DFS) rate was 69.4% for MIE and 57.2% for open surgery.
      Conclusions: For patients with locally advanced stage pT3 ESCC, MIE has
      perioperative outcomes comparable to those of open surgery without compromising
      recurrence or survival.

PMID- 29221272
TI  - Goal-directed fluid restriction using stroke volume variation and cardiac index
      during one-lung ventilation: a randomized controlled trial.
AB  - Background: Goal-directed therapy confers a strong prognosis in patients
      undergoing major cardiac or noncardiac surgery. The present study investigated
      whether intraoperative goal-directed fluid restriction (GDFR) using stroke volume
      variation (SVV) and cardiac index could improve oxygenation and postoperative
      outcome in patients undergoing one-lung ventilation (OLV). Methods: A Total of
      168 patients scheduled for elective thoracoscopic lobectomy under OLV were
      randomized into the GDFR protocol (group G) or conventional fluid therapy groups
      (group C). Patients in group C underwent conventional fluid therapy based on mean
      arterial pressure (MAP), central venous pressure (CVP), and urine volume, whereas
      those in group G received GDFR protocol associated with the SVV from 10-13% and
      the cardiac index was controlled at a minimum of 2.5 L/min/m2. The primary
      outcome variable was PaO2/FiO2. The secondary outcomes were other pulmonary
      variables and lung mechanics, inflammatory response, the incidence of
      postoperative pulmonary complications, and the length of hospital stay. Results:
      During surgery, the PaO2/FiO2 ratio in group G was more than that of group C at
      30 and 60 min after OLV, 10 min after re-expansion, and the end of the operation
      (259+/-29 vs. 314+/-34; 253+/-30 vs. 308+/-35; 341+/-34 vs. 394+/-39; 349+/-35
      vs. 401+/-39, respectively, all P<0.001). Compared to conventional fluid therapy,
      GDFR protocol also significantly improved the hemodynamic and lung mechanics with
      the initiation of OLV. The incidence of postoperative pulmonary complications
      such as acute lung injury and pneumonia, and the length of hospital stay were
      decreased by GDFR protocol as compared to conventional fluid therapy (all
      P<0.05). However, there were no significant differences between groups with
      respect to the concentration of serum tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), and interleukin-10 (IL-10). Conclusions: The GDFR protocol
      based on SVV and cardiac index applied in patients undergoing OLV improves
      intraoperative pulmonary oxygenation. It can also reduce the postoperative
      complications and length of hospital stay. However, the GDFR strategy cannot
      reduce the local or systemic inflammation. Trial registration: Chinese Clinical
      Trials Register ChiCTR-INR-16008288, Registered 20 April, 2016.

PMID- 29221273
TI  - Clinical outcomes of video-assisted thoracoscopic surgery esophagectomy for
      esophageal cancer: a propensity score-matched analysis.
AB  - Background: Minimally invasive esophagectomy theoretically offers advantages
      compared with open esophagectomy (OE). The aim of this study was to compare the
      early- and mid-term outcomes between video-assisted thoracoscopic surgery (VATS)
      esophagectomy (VE) and OE in patients with esophageal cancer. Methods: Between
      November 2011 and July 2015, a total of 172 patients were divided into two groups
      depending on the method of esophagectomy: the VE group (n=42) and the OE group
      (n=130). A propensity analysis that incorporated perioperative variables, such as
      age, sex, preoperative pulmonary function, Charlson comorbidity index, tumor
      location, histologic grade of the tumor, pathologic stage and operative procedure
      (Ivor Lewis or McKeown) was performed, and postoperative outcomes were compared.
      Results: Matching based on propensity scores produced 42 patients in each group
      for the analysis. After propensity matching, there were only two operative
      mortalities in the OE group, and both died of postoperative pneumonia. The
      overall incidence of postoperative complications was 38.1% (16 of 42) and 57.1%
      (24 of 42) in the VE group and in the OE group, respectively (P=0.088). The
      incidence of pulmonary complications was lower in the VE group than in the OE
      group (9.5% vs. 40.5%, P=0.004). The 2-year overall survival and disease-free
      survival were not different between the two groups (74.4% and 69.5% in the VE
      group, 69.5% and 69.8% in the OE group, P=0.865 and P=0.513, respectively).
      Conclusions: In select patients, superior short-term surgical results and equal
      oncological outcomes were achieved with VE compared with OE.

PMID- 29221274
TI  - Predictors of high flow nasal cannula failure in immunocompromised patients with
      acute respiratory failure due to non-HIV pneumocystis pneumonia.
AB  - Background: To evaluate the predictors of high flow nasal cannula (HFNC) failure
      in pneumocystis pneumonia (PCP) patients with acute respiratory failure (ARF).
      Methods: Fifty-two non-HIV-related PCP subjects were divided into a HFNC success
      group (44%) and a HFNC failure group (who required mechanical ventilation (MV)
      despite HFNC application) (56%). The clinical characteristics and physiologic
      effects were retrospectively reviewed and compared between the groups. Results:
      At baseline, the heart rate, alveolar-arterial PO2 difference [P(A-a)O2],
      Sequential Organ Failure Assessment (SOFA) score, and proportion of subjects who
      used vasopressors were significantly higher in the HFNC failure group than in the
      HFNC success group. The 60-day mortality was 52% in the HFNC failure group and
      13% in the HFNC success group (P=0.004). The results of the multivariate analysis
      indicated that the baseline SOFA score was independently associated with HFNC
      failure (adjusted odds ratio, 1.74 per each score unit increase; 95% CI, 1.05
      2.89; P=0.03). Repeated measures analysis of variance revealed that within 6 h of
      HFNC initiation, the mean PaO2/FiO2 ratio decreased and the mean P(A-a)O2
      increased rapidly in the HFNC failure group. Conclusions: Patients with ARF due
      to PCP subjected to HFNC therapy should be carefully monitored, and particular
      attention should be paid to those who had organ dysfunction and did not show
      early oxygenation improvement.

PMID- 29221275
TI  - Patterns of distant organ metastases in esophageal cancer: a population-based
      study.
AB  - Background: Esophageal cancer is the eighth most common cancer worldwide. The
      prognosis of esophageal cancer patients is dismal, especially those with distant
      organ metastasis. However, there are few studies describing the patterns of
      distant metastasis in esophageal cancer systematically. Methods: We gathered the
      data from Surveillance Epidemiology and End Results (SEER) database between 2010
      and 2013. Categorical variables were analyzed by the Pearson Chi square test, and
      continuous variables were analyzed by the two-sample t test. Survival estimation
      and comparison among different variables were performed using Kaplan-Meier
      method. A multivariable logistic regression model was used to calculate odds
      ratios (OR) for sex, age, anatomical site, and histological type on specific
      metastases. Proportional hazards regression model was conducted to obtain
      adjusted hazard ratio (HRs) for different predictors of overall survival.
      Results: A total of 9,934 patients were eligible. Liver was the most common
      metastatic site in the patients of esophageal cancer and followed by lung, bone
      and brain. Some clinical features, including age, sex, histology type and
      histologic grade were independent risk factors for different sites of metastasis.
      Younger age, poorer differentiation, adenoma type and more metastatic sites might
      lead to poorer prognosis. Conclusions: Our findings revealed the patterns of
      metastasis in esophageal cancer, which could help clinicians to identify patients
      with metastasis and provide proper treatment.

PMID- 29221276
TI  - Deep sternal wound infection after cardiac surgery in the Chinese population: a
      single-centre 15-year retrospective study.
AB  - Background: Deep sternal wound infection (DSWI) is a severe complication
      following cardiac surgery. A retrospective study was implemented to determine the
      risks and clinical characteristics of DSWI after cardiac operation in the Chinese
      population. Methods: We analysed 7,944 consecutive patients who underwent cardiac
      surgery via median sternotomy from January 2002 to December 2016 at our
      institution. Multiple logistic regression analysis was used to identify risk
      factors for DSWI. Results: A total of 106 patients (1.33%) suffered from DSWI;
      significant risk factors included body mass index (BMI) (P=0.02; OR=1.08; 95% CI:
      1.01-1.16) and reoperation (P<0.01; OR=5.93; 95% CI: 2.88-12.25). The most common
      bacterium involved in DSWI was staphylococcus aureus (23%). Among all DSWI
      patients, the overall survival rate of the group treated with flap reconstruction
      was significantly higher than that in the group treated with intravenous
      antibiotics and sternal debridement (87% vs. 59%, P=0.01). Conclusions: DSWI was
      associated with several risk factors. Effective intervention strategies could
      improve the outcome of patients undergoing cardiac surgery.

PMID- 29221277
TI  - Worse survival after curative resection in patients with pathological stage I non
      small cell lung cancer adjoining pulmonary cavity formation.
AB  - Background: A few investigators have suggested an association between lung cancer
      and pulmonary cavity. However, this clinical association and its carcinogenic
      correlations are not well recognized. This study aimed to clarify the clinical
      features and to demonstrate the associated survival outcomes after curative
      surgery in patients with early non-small cell lung cancer (NSCLC) adjoining
      pulmonary cavity formation. Methods: We retrospectively reviewed 275 patients
      with pathological stage I NSCLC by re-evaluating their chest computed tomography
      images. Among them, we detected NSCLC adjoining pulmonary cavity formation in 12
      (4.4%) patients. Results: The median follow-up period for all 275 patients was
      43.2 (range, 6.0-86.0) months. Of these patients, 6 (50.0%) in group CF (patients
      with NSCLC adjoining pulmonary cavity formation) and 19 (7.2%) in group C (the
      control group, n=263) died during the study period. Besides, 6 (50.0%) and 32
      (12.2%) patients in groups CF and C, respectively, exhibited recurrence of the
      primary lung cancer. The cumulative overall survival (OS) in groups CF and C at 5
      years was 37.0% and 91.7%, respectively (P<0.0001); the recurrence-free survival
      (RFS) in these groups at 5 years was 55.0% and 86.7%, respectively (P=0.001).
      Univariate analysis showed that male sex, smoking habits, non-adenocarcinoma, and
      presence of pulmonary cavity formation were associated with poor OS (P=0.008,
      P=0.001, P<0.0001, and P<0.0001, respectively). Multivariate analysis
      demonstrated that smoking, non-adenocarcinoma, and pulmonary cavity formation
      were independent prognostic factors predicting poor survival (P=0.043, P=0.004
      and P<0.0001, respectively). Conclusions: Our results suggest that patients with
      early-stage NSCLC adjoining pulmonary cavity formation have an increased risk of
      poor OS and RFS after surgical resection. Further prospective, multi
      institutional investigations and substantial clinical studies are warranted.

PMID- 29221278
TI  - Mitral valve repair versus replacement in elderly patients: a systematic review
      and meta-analysis.
AB  - Background: Although mitral valve repair (MVP) is generally accepted as the
      standard treatment for mitral valve disease, in older patients, there is
      increasing debate about whether MVP is superior to mitral valve replacement
      (MVR). We, therefore, performed a meta-analysis to compare MVP vs. MVR in the
      elderly population. Methods: We systematically searched PubMed, the Cochrane
      Library, and Scopus up to February 2017 and scrutinized the references of
      relevant literatures. Only studies of MVP vs. MVR in the elderly patients (aged
      70 years or older) that were published after 2000 were included. Results: The
      retrieval process yielded seven observational clinical studies with 1,809
      patients. Compared with MVR, MVP was associated with a significantly reduced 30
      day mortality [risk ratio (RR): 0.40, 95% confidence interval (CI): 0.25-0.64],
      with shorter duration of postoperative hospital stay (days) (weighted mean
      difference: -1.47, 95% CI: -2.47--0.48) and less postoperative complications (RR:
      0.69, 95% CI: 0.56-0.86). In addition, our study also demonstrated improved 1
      year (RR: 1.16, 95% CI: 1.08-1.24) and 5-year (RR: 1.26, 95% CI: 1.13-1.41)
      survival rates following MVP. There was no difference in reoperations between
      these two surgery approaches. Conclusions: The present meta-analysis indicates
      that elderly patients who receive MVP have better early and late outcomes than
      those undergoing MVR. MVP may be the preferred strategy for mitral valve surgery
      in the elderly population.

PMID- 29221279
TI  - Endoscopic naso-leakage drainage: a safe and effective method for the management
      of intrathoracic anastomotic leakage after esophagectomy.
AB  - Background: Intrathoracic anastomotic leakage (IAL) remains a major complication
      of esophagectomy. Main non-surgical options of management include chest drainage
      and endoscope interventions. This study is aim to present our experience and
      assess the efficacy of endoscopic naso-leakage drainage (ENLD) in patients with
      IAL. Methods: From June 2011 to January 2017, 67 patients who developed IAL after
      esophagectomy and managed by non-surgical approaches were analyzed
      retrospectively. IAL was confirmed by clinical presentations combined with the
      evidence of CT scan, radiography and endoscopy. Thirty-eight patients were
      treated by conventional chest drainage (CD group) and 29 patients underwent ENLD
      with or without chest drainage (ENLD group), while other treatments including
      enteral nutrition and antibiotics had no difference between the two groups. In
      ENLD group, a 12 Fr naso-leakage tube was placed through the leakage to the
      bottom of vomica under ultra-slim electronic gastroscope. The naso-leakage tube
      was then connected to a gastrointestinal decompression device for drainage and
      was also used for rinse. When the vomica diminished and the drainage was also
      clean, the naso-leakage tube could be pulled back gradually. Finally, healing of
      the leakage was confirmed endoscopically. Clinical records of the two groups were
      analyzed. Results: In ENLD group, naso-leakage tubes were successfully placed
      under endoscope in all 29 patients without any procedure-related complications.
      In CD group, the mortality is 7.9% (three patients) and five patients (13.2%)
      developed to systemic inflammatory response syndrome (SIRS) due to insufficient
      drainage. While in ENLD group, there was only one patient (3.4%) developed to
      SIRS and no death was observed, but the difference was not statistically
      significant. When compared with the CD group, the ENLD group had a shorter
      healing course (44.2+/-18.3 vs. 60.5+/-27.7 days, P=0.008), duration of
      antibiotics usage (16.4+/-7.8 vs. 11.8+/-3.8 days, P<0.001) and duration of fever
      (4.3+/-2.2 vs. 9.5+/-8.6 days, P=0.002). Conclusions: To our initial experience,
      ENLD is an ideal option with safety and efficacy in management of IAL after
      esophagectomy.

PMID- 29221280
TI  - Transmanubrial osteomuscular sparing approach for resection of cervico-thoracic
      lesions.
AB  - Background: To review our experience of transmanubrial osteomuscular sparing
      approach (TMA) for resection of various lesions involving the thoracic inlet and
      to prove the feasibility and safety of the approach. Methods: Retrospective
      review of 58 consecutive cases, from April 2007 to January 2016, with surgical
      resection of cervico-thoracic lesions via TMA. Results: There were 22 neurogenic
      tumors, 21 bronchogenic tumors, and 15 other cases in the study. There was no
      intraoperative or postoperative mortality. Mean postoperative stay was 10.5 days
      (3-33 days). Mean operation time was 179.0 mins (57-328 mins) and the mean volume
      of blood loss for bronchogenic tumors was 900 mL, which was similar to non
      bronchogenic tumors (474 mL, P=0.103). Moreover, patients with malignant tumors
      had more intraoperative blood loss than patients with benign diseases did (847
      versus 194 mL, P=0.001). R0 resection was achieved in 28 of 33 (84.8%) malignant
      cases. Tumor size was related to incomplete resection (8.19 vs. 5.72 cm, P=0.023)
      in malignancy. Five (8.6%) cases were complicated with chylothorax and all
      occurred in patients with left incision. All of 21 cases (100%) with brachial
      plexus compression symptom were relieved after surgery and 3 of 4 (75%) cases
      with Horner's syndrome were ameliorated postoperatively. Conclusions: TMA can be
      carried out safely in treating various cervico-thoracic lesions with good
      resection rate. Left side procedure should be cautious of thoracic duct injury.

PMID- 29221281
TI  - Is compensatory hyperhidrosis after thoracic sympathicotomy in palmar
      hyperhidrosis patients related to the excitability of thoracic sympathetic
      ganglions?
AB  - Background: The mechanism of compensatory hyperhidrosis remains unclear. The aim
      of this study was to explore the relationship between compensatory hyperhidrosis
      and thoracic sympathetic ganglion excitability to assess the effectiveness of
      thoracoscopic T4 sympathicotomy for treating palmar hyperhidrosis. Methods: Sixty
      six cases of T4 sympathetic ganglions were prospectively collected from patients
      with palmar hyperhidrosis who underwent thoracoscopic T4 sympathicotomy from 2013
      to 2016 in our department. The expression levels of choline acetyltransferase
      (ChAT), vasoactive intestinal peptide (VIP), and synaptophysin were detected
      using immunohistochemistry. Patients with palmar hyperhidrosis were followed-up
      for examination of postoperative sweating status. Results: Thirty-eight cases
      (57.6%) of compensatory hyperhidrosis were identified. Mild compensatory
      hyperhidrosis occurred in 26 patients (39.4%), moderate in 11 (16.7%), and severe
      in 1 (1.5%). The rate of compensatory hyperhidrosis was higher in patients with
      axilla hyperhidrosis than those without (76.0% vs. 46.3%, P=0.018). However, the
      clinical data were similar between the compensatory hyperhidrosis group and the
      no compensatory hyperhidrosis group. In addition, the ChAT, VIP, and
      synaptophysin expression levels were not significantly different between the two
      groups (P values of 0.356, 0.071, and 0.141, respectively). Furthermore, the
      ChAT, VIP, and synaptophysin expression levels in the mild group were similar to
      those observed in the moderate/intense group (P values of 0.089, 0.124, and
      0.149, respectively). The remission rate was 100% in palmar hyperhidrosis, 48.2%
      (27/56) in pedal hyperhidrosis, 56.0% (14/25) in axilla hyperhidrosis and 88.9%
      (16/18) in skin symptoms. No signs of chapped skin on the palms were found.
      Conclusions: There was no significant correlation between compensatory
      hyperhidrosis and thoracic sympathetic ganglion excitability; however,
      compensatory hyperhidrosis is more likely to simultaneously occur in patients
      with axilla hyperhidrosis. The satisfactory efficacy of thoracoscopic T4
      sympathicotomy indicates that it may an ideal technique for palmar hyperhidrosis.

PMID- 29221282
TI  - Induction chemoradiotherapy using docetaxel and cisplatin with definitive-dose
      radiation followed by surgery for locally advanced non-small cell lung cancer.
AB  - Background: Induction chemoradiotherapy (CRT) followed by surgery is a
      therapeutic option for locally advanced non-small cell lung cancer (LA-NSCLC).
      Typically, around 40-50 Gy of radiation is applied as the induction-dose;
      however, a definitive-dose (DD) of radiation (60 Gy or higher) is occasionally
      applied to increase local control. We investigated the impact of induction CRT
      with DD radiation in LA-NSCLC patients treated with a single regimen of docetaxel
      and cisplatin. Methods: We reviewed 110 patients with LA-NSCLC who underwent
      induction CRT followed by surgery using a single regimen (docetaxel and
      cisplatin) between January 1999 and December 2014 at our hospital. The clinical
      outcomes of a DD group (60 Gy or higher, n=11) and a non-DD group (less than 60
      Gy, n=99) were investigated using a propensity score (PS)-matched analysis.
      Results: An advanced clinical stage was significantly more common in the DD group
      than in the non-DD group (P=0.033). Before and after the PS-matching based on
      seven factors including clinical stage, there was no significant difference in
      the rates of postoperative (PO) complication, mortality, 5-year overall survival
      (OS), or 5-year recurrence-free survival (RFS) between the two groups. After the
      PS-matching, the pathological complete response (CR) rate was significantly
      higher in the DD group than in the non-DD group [50% (n=5/10) vs. 0% (n=0/10),
      P=0.033]. Conclusions: Induction CRT followed by surgery using docetaxel and
      cisplatin with DD radiation can be performed safely and is associated with a
      higher pathological CR rate than that attained using non-DD radiation in LA-NSCLC
      patients.

PMID- 29221283
TI  - Effectiveness and safety of simultaneous hybrid thoracoscopic endocardial
      catheter ablation of atrial fibrillation in obese and non-obese patients.
AB  - Background: We evaluated the safety and effectiveness of the hybrid thoracoscopic
      endocardial epicardial ablation technique for the treatment of atrial
      fibrillation (AF) in obese versus non-obese patients. Methods: Between January
      2010 and January 2015, a cohort of 61 patients were retrospectively identified to
      undergo ablation of AF as a stand-alone procedure using a thoracoscopic, hybrid
      epicardial-endocardial technique. All patients underwent continuous 7-day Holter
      monitoring at 3, 6 months, 1 year and yearly thereafter. Results: A total of 40%
      of the obese cohort had persistent or long-standing AF, compared to 54.9% of the
      non-obese cohort. There were no deaths or conversion to cardiopulmonary bypass
      required. At 3-year follow-up, 60% of the obese group were in sinus rhythm (SR)
      with no episode of AF, atrial flutter or atrial tachycardia lasting 30 s off anti
      arrhythmic drugs. This was compared to 70.6% in the non-obese group, with no
      significant difference between the groups (P=0.468). For success rates on anti
      arrhythmic drugs, this was 80% in the obese group compared to 86% in the non
      obese group at 3-year follow-up (P=0.637). No patient died and no
      thromboembolic/bleeding events or procedure-related complications occurred during
      the follow-up. Conclusions: In a retrospective cohort with approximately half
      with persistent or long-standing AF, thoracoscopic hybrid epicardial endocardial
      ablation proved to be equally effective and safe in obese versus non-obese
      patients. Current preliminary findings require further validation in multi
      institutional prospective studies with larger sample sizes.

PMID- 29221284
TI  - Comparison of perioperative outcomes following hybrid minimally invasive versus
      open Ivor Lewis esophagectomy for esophageal cancer.
AB  - Background: The outcomes of various minimally invasive esophagectomy (MIE)
      procedures for esophageal cancer have been reported; however, those of the hybrid
      approach are lacking. This study aimed to assess the impacts of hybrid minimally
      invasive Ivor Lewis esophagectomy (HIL, laparoscopy and right thoracotomy) for
      esophageal cancer on perioperative outcomes compared with the open approach.
      Methods: This was a retrospective study of 153 patients who underwent Ivor Lewis
      esophagectomy for squamous cell carcinoma between January 2008 and December 2016.
      Patients who received neoadjuvant treatment prior to surgery (n=22) and underwent
      complete minimally invasive procedures (n=16) were excluded. Clinical
      characteristics and perioperative outcomes of patients who underwent HIL (n=53)
      were compared with findings in patients who underwent open Ivor Lewis
      esophagectomy (OIL, n=62). Results: There were 112 men (97.4%) and 3 women (2.6%)
      with a median age of 66 years (range, 45-83 years). The HIL and OIL groups were
      comparable with respect to age, sex, preoperative pulmonary function, location of
      the tumor, and preoperative laboratory findings. There was no significant
      difference between the two groups regarding surgical data, except for pyloric
      management. Postoperative complications occurred in 17 (32.1%) and 23 (37.1%)
      patients in the HIL and OIL groups, respectively (P=0.573); in-hospital mortality
      rates were 3.8% and 8.1%, respectively (P=0.337). HIL group patients had higher
      albumin (3.3 vs. 2.9 g/dL; P<0.001) and lower C-reactive protein (6.4 vs. 8.1
      mg/L; P<0.001) postoperatively. The length of hospital stay was shorter in the
      HIL group (13.5 vs. 19.2 days; P=0.002). Conclusions: Compared with the
      conventional open approach, HIL for esophageal cancer showed better postoperative
      nutritional and inflammatory status, resulting in shorter hospital stays.
      However, further studies are required to evaluate the long-term oncologic
      outcomes of this hybrid approach.

PMID- 29221285
TI  - Robot-assisted thoracic surgery for complex procedures.
AB  - Background: As an option for minimally invasive thoracic surgery, robot-assisted
      thoracic surgery (RATS) has shown comparable perioperative outcomes to those
      achieved by traditional video-assisted thoracic surgery (VATS). It is unknown
      whether RATS might have any potential benefits in more complex thoracic surgical
      procedures, which usually require open surgery instead of VATS. The current study
      presents a preliminary result regarding the use of RATS in complex thoracic
      operations in an attempt to address this unresolved question. Methods: Data from
      a prospectively collected and maintained surgical database were collected on
      patients who underwent RATS between February 2012 and August 2014. We defined
      complex RATS as those operations involving difficult dissections, complex sutures
      or excision of very large tumors (>8 cm) which would have required open surgery
      in our hospital before the introduction of RATS. The characteristics and peri
      operative outcomes of patients receiving complex RATS were reviewed. Results: Of
      the 120 patients undergoing RATS, 30 of them were classified as having undergone
      complex RATS, 21 to remove lung tumors and 9 to remove mediastinal tumors. The
      indications for complex RATS included 21 difficult dissections, 10 complex
      sutures, and 7 very large tumors (8 patients had two indications). There are
      three conversions to thoracotomy for pulmonary arterial bleeding. There was one
      mortality resulted from post-pneumonectomy pulmonary hypertension and sepsis.
      Patients with difficult dissection had longer operative time and hospital stay,
      and more bleeding and postoperative morbidity. Conclusions: RATS for complex
      thoracic procedures is feasible, especially for complex suturing and excision of
      very large mediastinal tumors, but more attention is needed for patients needing
      difficult dissections. Advanced preparation for conversion is necessary during
      this difficult operation.

PMID- 29221286
TI  - Automatic Lung-RADSTM classification with a natural language processing system.
AB  - Background: Our aim was to train a natural language processing (NLP) algorithm to
      capture imaging characteristics of lung nodules reported in a structured CT
      report and suggest the applicable Lung-RADSTM (LR) category. Methods: Our study
      included structured, clinical reports of consecutive CT lung screening (CTLS)
      exams performed from 08/2014 to 08/2015 at an ACR accredited Lung Cancer
      Screening Center. All patients screened were at high-risk for lung cancer
      according to the NCCN Guidelines(r). All exams were interpreted by one of three
      radiologists credentialed to read CTLS exams using LR using a standard reporting
      template. Training and test sets consisted of consecutive exams. Lung screening
      exams were divided into two groups: three training sets (500, 120, and 383
      reports each) and one final evaluation set (498 reports). NLP algorithm results
      were compared with the gold standard of LR category assigned by the radiologist.
      Results: The sensitivity/specificity of the NLP algorithm to correctly assign LR
      categories for suspicious nodules (LR 4) and positive nodules (LR 3/4) were
      74.1%/98.6% and 75.0%/98.8% respectively. The majority of mismatches occurred in
      cases where pulmonary findings were present not currently addressed by LR.
      Misclassifications also resulted from the failure to identify exams as follow-up
      and the failure to completely characterize part-solid nodules. In a sub-group
      analysis among structured reports with standardized language, the sensitivity and
      specificity to detect LR 4 nodules were 87.0% and 99.5%, respectively.
      Conclusions: An NLP system can accurately suggest the appropriate LR category
      from CTLS exam findings when standardized reporting is used.

PMID- 29221288
TI  - Pleurodesis: a comparison of two sclerosing agents for pleural effusions in
      Mozambique.
AB  - Background: Pleural effusions constitute one of the most frequent pathologies
      encountered in the pulmonary service of Maputo Central Hospital (MCH) in
      Mozambique. Bleomycin and talc are commonly used for pleurodesis, but cost
      prohibitive, therefore we aimed to retrospectively compare the efficacy and
      safety of sodium hydroxide (NaOH) with bleomycin for pleurodesis. Methods: Case
      records of pleurodesis using bleomycin and NaOH from 2002 to 2013 were reviewed.
      Standard of care for pleurodesis for recurrent pleural effusions at MCH was
      developed using the materials available. NaOH remained the agent of choice until
      2006 when bleomycin became available. Clinical data regarding general
      complications, rate of success and lung expansion were noted for every patient
      who underwent pleurodesis at MCH during this time frame. Results: Review of
      pleurodesis at MCH revealed 24 cases using bleomycin and 23 cases using NaOH as
      the sclerosing agent. Patient characteristics were balanced between the two
      groups with majority of pleural effusions malignant in etiology. Conclusions:
      There was no statistically significant difference between the use of bleomycin
      and NaOH as defined by lung expansion. General complications were observed less
      frequently in 2 (10%) of patients treated with NaOH compared with 8 (38%) of
      patients using bleomycin. Only three patients presented with recurrent pleural
      effusion after pleurodesis with NaOH. NaOH may offer a low cost alternative
      sclerosing agent for resource limited areas.

PMID- 29221287
TI  - Anti-cancer activity of dose-fractioned mPE +/- bevacizumab regimen is paralleled
      by immune-modulation in advanced squamous NSLC patients.
AB  - Background: Results from the BEVA2007 trial, suggest that the metronomic
      chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/-
      bevacizumab, a monoclonal antibody to the vascular endothelial growth factor
      (VEGF), shows anti-angiogenic and immunological effects and is a safe and active
      treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried
      out a retrospective analysis aimed to evaluate the antitumor effects of this
      treatment in a subset of patients with squamous histology. Methods: Retrospective
      analysis was carried out in a subset of 31 patients with squamous histology
      enrolled in the study between September 2007 and September 2015. All of the
      patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral
      etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5
      mg/kg on the day 3q21 (mPEBev regimen). Results: This treatment showed a disease
      control rate of 71% with a mean progression free survival (PFS) and overall
      survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6
      patients showing a remarkable tumor shrinkage, underwent to radical surgery,
      attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and
      log-rank test identified the longest survival in patients presenting low baseline
      levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A
      (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic
      cells (DCs) (P=0.03). Conclusions: These results suggest that the mPE +/-
      bevacizumab regimen is feasible and should be tested in comparative trials in
      advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects
      strongly suggest the investigation in sequential combinations with immune check
      point inhibitors.

PMID- 29221289
TI  - Features of rheumatic mitral valves and a grading system to identify suitable
      repair cases in China.
AB  - Background: We aimed to assess the pathological characteristics of rheumatic
      mitral valve disease in Chinese patients and formulate a pathological grading
      system to identify cases suitable for rheumatic mitral valve repair (rMVP).
      Methods: Nearly 5 years of follow-up data on patients who underwent rMVP were
      analysed. A Kaplan-Meier survival curve for freedom from reoperation and valve
      failure was constructed. A pathological grading system of rheumatic mitral valve
      lesions (PGSRMVL) was developed based on the pathological characteristics of
      rheumatic mitral valve disease and tested by receiver operating characteristics
      (ROCs) curve analysis. Predictors of endpoints for rheumatic repair were
      analysed. Results: From January 2012 to June 2016, 179 patients underwent rMVP in
      our centre. The mean follow-up duration was 24+/-14 months. A left atrial
      anterior and posterior diameter >60 mm was an independent predictor for the 16
      endpoints [hazard ratio (HR) =3.884, P=0.029]. Between 2015 and 2016, 126
      consecutive pathological characteristics of rheumatic mitral valve were evaluated
      (61 and 65 repair and replacement cases, respectively). The ROCs area under the
      curve was 0.891 for the correlation between the pathological score and successful
      repair (cut-off point, 17.5; sensitivity, 78%; specificity, 85.2%). Seven lesions
      had higher ratios in the replacement group than the repair group. Commissural
      fusion/calcification and main chordae tendineae fusion/calcification were the
      most common severe pathological lesions. Conclusions: The main pathological
      characteristics of rheumatic mitral valve disease in Chinese patients are
      commissure and sub-valvular apparatus lesions. Most patients can be appropriately
      treated via commissurotomy and leaflet thinning. Severe calcification of the
      commissure and sub-valvular apparatus can considerably decrease the odds of a
      successful repair. The median follow-up results of rheumatic mitral repair are
      considered satisfactory for the pathological characteristics in Chinese patients.

PMID- 29221290
TI  - Should sinus of Valsalva be preserved in patients with bicuspid aortic valve and
      aortic dilation?
AB  - Background: It is recommended that dilated ascending aortas (>=45 mm) should be
      replaced at the time of aortic valve replacement (AVR) for bicuspid aortic valve
      (BAV). The risk of progressive sinus of Valsalva dilatation after AVR and
      ascending aorta replacement is less clear. Methods: We identified 156 patients
      (age 56.2+/-10.8 years, 46 females) who underwent AVR and ascending aorta
      replacement in our institution from 2010-2014, 124 (79%) of whom had BAV. Aortic
      root and ascending aorta sizes were determined from preoperative and the most
      recent echocardiograms. The mean follow-up time was 34.4+/-22.3 months, and 97%
      of patients completed the follow-up. Results: The operative mortality rate was
      1.3%. During a follow-up of up to 75.2 months, there were no late reoperations
      for aortic root dissection or rupture. The mean preoperative aortic root
      diameters in the tricuspid aortic valve (TAV) and BAV groups were 42.2+/-5.4 and
      37.5+/-5.4 mm, respectively (P=0.69). After operation, most of the patients had
      reduced aortic root sizes, as the mean postoperative root diameters in the TAV
      and BAV groups were 39.6+/-5.2 and 35.7+/-5.1 mm, respectively (P=0.99).
      Conclusions: To avoid the risks associated with aortic root replacement, it is
      reasonable to spare the aortic roots in the setting of AVR and ascending aorta
      replacement for BAV with a dilated ascending aorta and relatively normal sinuses
      of Valsalva.

PMID- 29221291
TI  - Airway stenting in patients requiring intubation due to malignant airway
      stenosis: a 10-year experience.
AB  - Background: Critically ill patients with severe acute respiratory failure due to
      malignant airway stenosis often require emergency intubation and mechanical
      ventilation. Urgent intervention is necessary for the survival of such patients.
      The aim of this study was to determine the efficacy and outcomes of airway
      stenting in patients with malignant airway stenosis requiring emergency
      intubation. Methods: Patients with malignant airway stenosis who underwent
      emergency intubation prior to airway stent placement from September 2005 to
      September 2015 in a single center were retrospectively reviewed. All stenting
      procedures were performed using both rigid and flexible bronchoscopes under
      general anesthesia. Results: Thirty patients with malignant airway stenosis (17
      with lung cancer, 6 with esophageal cancer, and 7 with other types of malignancy)
      who required emergency intubation prior to stenting procedures (silicone stenting
      in 23 and metallic stenting in 7) were analyzed. Extubation within 48 hours after
      stenting could be performed in 28 of 30 patients (93%). Of the 21
      chemoradiotherapy-naive patients, 18 (86%) received chemotherapy and/or radiation
      therapy after stenting. No significant complications occurred during the stenting
      procedures. The median survival after stenting was 198 days (range, 13-3,009
      days). Conclusions: Airway stenting facilitates extubation in critically ill
      patients with malignant central airway stenosis. It plays an important role as a
      bridge to additional tumor-specific therapies, especially in chemoradiotherapy
      naive patients.

PMID- 29221292
TI  - A comparative study of conventional cytology and cell block method in the
      diagnosis of pleural effusion.
AB  - Background: In a patient with pleural effusion, cytological study (CS) is one of
      the most useful investigations, especially when malignancy is suspected. Instead
      of applying only CS, the pleural fluid can be further processed using the cell
      block (CB) technique, which may augment the diagnostic utility. The aim of this
      study was to compare the diagnostic yields of CS, CB, and the combination of
      both, regardless of the etiology of pleural effusion. Methods: A cross-sectional
      study was conducted on patients with pleural effusions who underwent
      thoracentesis from June 2015 to May 2016. All samples were submitted for routine
      biochemical analysis, CS, and CB histology. The results of cytopathological
      studies were compared to the final diagnoses. Results: Out of a total of 353
      samples, the final diagnoses included 278 (78.8%) malignancies, 41 (11.6%)
      infectious diseases, 16 (4.5%) other inflammatory diseases, and 18 (5.1%)
      transudative pleural effusions. CS and CB provided a similar diagnostic yield
      (48.7% vs. 49.9%, P=0.69), while the combination of both gave a higher yield
      (57.2%) (P<0.001, compared with CS). Among 278 malignant pleural effusions (MPE),
      the diagnostic yields of CS and CB were 61.2% and 61.9%, respectively. Combined
      CS and CB improved the diagnostic yield to 71.2% (P<0.001). However, both CS and
      CB had low diagnostic yields in infectious pleuritis, other inflammatory
      diseases, and transudative pleural effusions. Conclusions: In MPE, CB provides a
      similar diagnostic performance to CS, while application of both techniques can
      significantly increase the diagnostic yield. However, in other pleural diseases,
      CB and CS had limited values in diagnosis.

PMID- 29221293
TI  - Distance-saturation product of the 6-minute walk test predicts mortality of
      patients with non-cystic fibrosis bronchiectasis.
AB  - Background: Previous surveillance methods to monitor the prognoses of patients
      with bronchiectasis are too complex for use in daily practice. The 6-minute walk
      test (6MWT) is a simple exercise test to predict the prognosis of chronic
      obstructive airway disease and numerous chronic lung diseases, including
      idiopathic pulmonary fibrosis. No studies have investigated exercise-induced
      oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to
      predict the prognoses of patients with bronchiectasis. Methods: This was a
      prospective study to identify correlations between variables of 6MWT and
      mortality in patients with bronchiectasis over a 6-year period. The study cohort
      included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who
      were regularly evaluated for functional status via 6-minute walk distance (6MWD),
      spirometry, BODE index, EID, and DSP. Results: Of the 69 patients, 9 (13%) died
      and 60 (87%) survived during the 6-year follow-up period. The percentage of EID
      was higher [7 of 9 patients (78%) vs. 22 of 60 patients (27%), P=0.003] in the
      non-survivors group. The 6MWD (467.9+/-77.1 vs. 363.7+/-126.7 m, P=0.001) was
      higher in the survivors group. DSP was significantly lower in the non-survivors
      group (411.0+/-78.4 vs. 283.9+/-90.0 m%, P<0.001). Multivariate analysis showed
      that DSP (OR =0.983; 95% CI: 0.974-0.993, P=0.001) was the best parameter of 6MWT
      to predict mortality. Patients with a lower DSP of <280 m% were at a 66.5-fold
      greater risk (OR =66.5; 95% CI: 9.4-469.2) of 6-year mortality compared with
      those with DSP >280 m% (P<0.001). Conclusions: DSP is a simple parameter to
      predict 6-year mortality in patients with non-CF bronchiectasis.

PMID- 29221294
TI  - Using M-mode ultrasonography to assess diaphragm dysfunction and predict the
      success of mechanical ventilation weaning in elderly patients.
AB  - Background: Ultrasonography (US) is a non-invasive and commonly available bedside
      diagnostic tool. The aim of this study was to assess the utility of M-mode US on
      ventilator weaning outcomes in elderly patients. Methods: This was a single
      center, prospective, observational study in patients aged 80 years or older who
      were in the medical intensive care unit, had undergone mechanical ventilation for
      >48 hours, and met the criteria for a spontaneous breathing trial (SBT). For 30
      minutes at the start of SBT, each hemi-diaphragmatic movement and the velocity of
      contraction were evaluated by M-mode US. The the area under the receiver
      operating characteristic curve (AUROC) was calculated to determine the ability
      for measured variables to predict successful ventilator weaning. Results: Forty
      patients were enrolled and assessed, grouped by those who had US-diagnosed
      diaphragm dysfunction (DD; 30/40; 75%) and those who did not (10/40; 25%).
      Patients with DD had a significantly longer total mechanical ventilation duration
      (536.4+/-377.05 vs. 250+/-109.02 hours, P=0.02) and weaning time (425.9+/-268.31
      vs. 216.0+/-134.22 hours, P=0.002) than patients without DD. Patients with DD
      also had a higher incidence of weaning failure than patients without DD (24/30
      vs. 4/10, P=0.017). Analysis of the receiver operating characteristic (ROC) curve
      (ROC) curve showed that the optimal cut-off values to predict weaning success
      were >10.7 mm for the right diaphragmatic movement, and >21.32 mm/s for the right
      diaphragmatic velocity of contraction; AUROC were 0.839 (95% CI, 0.689-0.936) and
      0.833 (95% CI, 0.682-0.932), respectively. The sensitivity, specificity, positive
      and negative likelihood ratios for predicting weaning success were 83.33% vs.
      66.67%, 75.00% vs. 92.86%, 3.33 vs. 9.33, and 0.22 vs. 0.36, for right
      diaphragmatic movement and diaphragmatic contraction velocity, respectively.
      Conclusions: When assessed by M-mode US, DD appeared to be common in ventilated
      patients aged 80 years or older and was associated with a higher incidence of
      weaning failure. Larger right diaphragmatic movements or faster right
      diaphragmatic contraction velocity appeared to be good predictors of mechanical
      ventilation weaning success in elderly patients.

PMID- 29221295
TI  - Contralateral thoracoscopic lobectomy in postlobectomy patients.
AB  - Background: It is difficult to perform thoracoscopic lobectomy in patients with a
      history of contralateral lobectomy, as stable oxygenation is not always
      maintained under conditions of one-lung ventilation during surgery. Methods: This
      study evaluated 14 patients who underwent thoracoscopic lobectomy after
      previously undergoing contralateral lobectomy at a single institution between
      2008 and 2015. Results: Among 14 patients who had previously received
      contralateral lobectomy, 4 were unable to maintain sufficient perioperative
      oxygenation with usual one-lung ventilation. The predicted pulmonary function
      before surgery in these patients was as follows: both (I) predicted postoperative
      forced expiratory volume in 1 second <800 mL/m2; and (II) <=5 contralateral
      residual segments for ventilation. Regarding special oxygenation techniques, two
      underwent selective ventilation using lobe-selective bronchial blockade, one
      underwent intermittent positive airway pressure for operative side lung, and one
      underwent high-frequency jet ventilation for operative residual lobe.
      Conclusions: When performing thoracoscopic lobectomy in patients with a history
      of contralateral lobectomy, a careful evaluation of the preoperative pulmonary
      function is needed.

PMID- 29221296
TI  - Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable
      esophageal squamous cell carcinoma undergoing esophagectomy with or without
      neoadjuvant concurrent chemoradiotherapy.
AB  - Background: The objective of this study was to appraise the prognostic role of
      initial pan-endoscopic tumor length at diagnosis within or between operable
      esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or
      neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy.
      Methods: Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer
      Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery
      group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were
      retrospectively collected. Prognostic variables, including initial pan-endoscopic
      tumor length at diagnosis (sub-grouped <=3, 3-5 and >5 cm), status of
      circumferential resection margin (CRM), and pathological T/N/M-status and cancer
      stage, were appraised within or between surgery and nCCRT-surgery groups.
      Results: Within surgery group, longer initial pan-endoscopic tumor length at
      diagnosis (<=3, 3-5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an
      independent prognostic factor that correlated with advanced T/N/M-status, late
      cancer stage, and CRM invasion (all's P<0.001). Based on the initial pan
      endoscopic tumor length at diagnosis <=3, 3-5 and >5 cm, nCCRT-surgery group had
      a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did
      surgery group, respectively. For those with initial pan-endoscopic tumor length
      at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and
      stage 0 (all's P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery
      group. Conclusions: Initial pan-endoscopic tumor length at diagnosis could be a
      criterion to select proper ESCC cases for nCCRT followed by esophagectomy to
      improve survival and reduce CRM invasion.

PMID- 29221297
TI  - Current status of asthma care in South Korea: nationwide the Health Insurance
      Review and Assessment Service database.
AB  - Background: Quality control is important for patients with asthma because of its
      prevalence and because the social burden is substantial. This study analyzed the
      Health Insurance Review and Assessment Service (HIRA) database to assess asthma
      quality control in South Korea. Methods: We investigated the HIRA nationwide
      database for reimbursed insurance claims from all medical institutions in South
      Korea from July 2013 to June 2014. The number of patients with asthma were
      evaluated and the medical institutions were categorized by type of medical
      institution. Asthma care quality was assessed by measuring the performance rate
      on pulmonary function test (PFT) and investigating prescriptions for asthma
      medications. Results: A total of 16,804 medical institutions and 831,613 patients
      were included in this study. Among them, primary health clinics accounted for
      87.75% of all medical institutions and 82.50% of patients were treated in a
      primary health clinic. The overall PFT performance rate was 23.47%, which was
      highest in tertiary hospitals (80.59%) and relatively lower in primary health
      clinics (17.06%). Oral agents were prescribed to 93.96% of patients, whereas
      inhaled agents were prescribed to only 30.34%. Oral corticosteroids were
      prescribed to 40.61% of patients, leukotriene antagonists to 48.78%, and inhaled
      corticosteroids (ICS) to 25.37% of patients by drug category. Conclusions: Most
      patients with asthma were treated in primary health clinics rather than higher
      class medical institutions. Asthma quality control was poor regarding usage of
      diagnostic measures and prescribed medications.

PMID- 29221298
TI  - The Redax(r) Coaxial Drain in pulmonary lobectomy: a study of efficacy.
AB  - Background: Pleural drainage is required after pulmonary lobectomy to evacuate
      air-leak and fluid. We compared the performance of the new Redax(r) Coaxial Drain
      (CD) (Redax, Mirandola, Italy) with a standard chest tube (CT) in terms of fluid
      and air-leak evacuation. Methods: Fifty-two patients receiving a 24-F CD under
      water-seal after pulmonary lobectomy through open surgery or video-assisted
      thoracic surgery (VATS) were matched according to demographic, clinical and
      pathological variables with 104 patients receiving a 24-F CT. Fluid evacuation
      and post-operative day 0 (POD0) fluid evacuation rate, air-leak rate, tension
      pneumothorax or increasing subcutaneous emphysema, tube occlusion at removal,
      visual analog scale (VAS) score at rest and during cough, chest drain duration,
      pleural fluid accumulation or residual pleural cavity after tube removal, post
      operative morbidity and mortality rate were recorded and compared between the two
      groups. Results: No differences were recorded in post-operative morbidity and
      mortality rates. Fluid drainage rates on POD0 were significantly higher in CD
      group (73% vs. 48%; P=0.004); air-leak occurrence was similar in both groups and
      no differences were recorded in terms of tension pneumothorax or increasing
      subcutaneous emphysema rates; VAS score was lower for CD when compared with CT
      and it reached significant difference in the subgroups of patients operated on by
      VATS; no cases of occlusion at removal were recorded in CD patient. Conclusions:
      Redax(r) CD is safe and efficient in air-leak and fluid evacuation; due to its
      design and constituting material it is superior to standard CTs in terms of fluid
      evacuation rate and patient post-operative comfort.

PMID- 29221299
TI  - Surgical site infections after lung resection: a prospective study of risk
      factors in 1,091 consecutive patients.
AB  - Background: To assess incidence and risk factors of surgical site infections
      (SSI) (wound infection, pneumonia, empyema) in a monocentric series of patients
      undergoing lung resection over a decade. Methods: All patients undergoing lung
      resection at our institution in 2006-2015 [wedge resection, n=579; lobectomy,
      n=472 (12% after chemo/radiotherapy); pneumonectomy, n=40 (47% after
      chemo/radiotherapy)], were prospectively enrolled. Perioperative SSI risk factors
      were recorded: age, gender, blood haemoglobin, lymphocyte count, serum albumin,
      forced expiratory volume in 1 second percentage (FEV1%) of predicted, antibiotic
      prophylaxis, length of stay, diabetes, malignancy, steroid therapy, induction
      chemo/radiotherapy, resection in 2006-2010/2011-2015, urgent/elective procedure,
      videothoracoscopic/open approach, resection type, operative time. SSIs diagnosed
      within 30 days from surgery were prospectively recorded and association with risk
      factors was evaluated. Results: Of the 1,091 resected patients [median age, 65
      (range, 13-91) years; male, 74%; malignancy, 65%], 124 (11.4%) developed one or
      more SSI. Wound infection, pneumonia and empyema rates were respectively 3.2%,
      8.3% and 1.9%, stable through the decade. Overall infection rates after wedge
      resection, lobectomy and pneumonectomy were 4.8%, 17.4% and 35.0%, respectively.
      Thirty-day postoperative mortality was 0.6%; of the 7 deaths, 4 were causally
      related with SSI. Multivariable analysis showed that male gender, diabetes,
      preoperative steroids, induction chemo/radiotherapy, missed antibiotic
      prophylaxis and resection type were independent risk factors for overall SSI.
      Conclusions: SSI rates after lung resection were stable over the decade. The
      observed 11.4% frequency of SSI indicates that postoperative infections remain a
      relevant issue and a predominant cause of mortality after lung surgery. Focusing
      on SSI risk factors that are perioperatively modifiable may improve surgical
      results.

PMID- 29221300
TI  - Comparison of continuous compression with regular ventilations versus 30:2
      compressions-ventilations strategy during mechanical cardiopulmonary
      resuscitation in a porcine model of cardiac arrest.
AB  - Background: A compression-ventilation (C:V) ratio of 30:2 is recommended for
      adult cardiopulmonary resuscitation (CPR) by the current American Heart
      Association (AHA) guidelines. However, continuous chest compression (CCC) is an
      alternative strategy for CPR that minimizes interruption especially when an
      advanced airway exists. In this study, we investigated the effects of 30:2
      mechanical CPR when compared with CCC in combination with regular ventilation in
      a porcine model. Methods: Sixteen male domestic pigs weighing 39+/-2 kg were
      utilized. Ventricular fibrillation was induced and untreated for 7 min. The
      animals were then randomly assigned to receive CCC combined with regular
      ventilation (CCC group) or 30:2 CPR (VC group). Mechanical chest compression was
      implemented with a miniaturized mechanical chest compressor. At the same time of
      beginning of precordial compression, the animals were mechanically ventilated at
      a rate of 10 breaths-per-minute in the CCC group or with a 30:2 C:V ratio in the
      VC group. Defibrillation was delivered by a single 150 J shock after 5 min of
      CPR. If failed to resuscitation, CPR was resumed for 2 min before the next shock.
      The protocol was stopped if successful resuscitation or at a total of 15 min. The
      resuscitated animals were observed for 72 h. Results: Coronary perfusion
      pressure, end-tidal carbon dioxide and carotid blood flow in the VC group were
      similar to those achieved in the CCC group during CPR. No significant differences
      were observed in arterial blood gas parameters between two groups at baseline, VF
      6 min, CPR 4 min and 30, 120 and 360 min post-resuscitation. Although
      extravascular lung water index of both groups significantly increased after
      resuscitation, no distinct difference was found between CCC and VC groups. All
      animals were successfully resuscitated and survived for 72 h with favorable
      neurologic outcomes in both groups. However, obviously more numbers of rib
      fracture were observed in CCC animals in comparison with VC animals. Conclusions:
      There was no difference in hemodynamic efficacy and gas exchange during and after
      resuscitation, therefore identical 72 h survival with intact neurologic function
      was observed in both VC and CCC groups. However, the incidence of rib fracture
      increases during the mechanical CPR strategy of CCC combined with regular
      ventilations.

PMID- 29221301
TI  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a
      powerful tool for identification of Corynebacterium species.
AB  - Background: Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) is a powerful tool that has initiated a revolution in
      the clinical microbiology laboratory for identification of nosocomial pathogens.
      The efficacy of MALDI-TOF MS produced by bioMerieux, Marcy l'Etoile, France
      (VITEK MS) for detecting Corynebacterium remains unknown. Methods:
      Corynebacterium isolates were isolated from clinical specimen in a tertial
      teaching hospital from 2012 to 2013. All strains confirmed by rpoB sequencing
      were identified by API Coryne (bioMerieux), Phoenix (BD) and VITEK MS,
      respectively. The coincidence rate was used to evaluate the consistency and
      accuracy across three methods. Results: In all, 75 Corynebacterium isolates were
      collected in this study. The dominant isolates were Corynebacterium striatum
      (58.7%), Corynebacterium jeikeium (16.0%), Corynebacterium amycolatum (5.3%),
      Corynebacterium urealyticum (5.3%), Corynebacterium glucuronolyticum (2.7%) and
      Corynebacterium minutissimum (2.7%). We found that there was no significant
      difference in the identification of corynebacterium to genus level by MS (100%,
      75/75) or Phoenix (93.3%, 70/75) (P=0.058). However, 92.0% (69/75) strains were
      successfully identified to species by MS while which by Phoenix and API was 78.7%
      and 65.3% respectively. Compared with gene sequencing, the coincidence rate of
      identification by MS was significantly higher than Phoenix (P=0.036) and API
      (P<0.001). Compared with API Coryne (bioMerieux) and Phoenix, VITEK MS shown
      significant shorter detecting period and less cost. Conclusions: VITEK MS was a
      powerful tool, which could be applied in clinical laboratory, improving the
      diagnosis for Corynebacterium infection.

PMID- 29221304
TI  - Microinvasive segmentectomy in a sculpting manner: a case of VATS left S1+2
      segmentectomy.
AB  - A ground-glass opacity (GGO) lesion was discovered in a 64-year-old female 1 year
      ago. One month before administration, a follow-up CT showed the lesion in the
      apical segment of left upper lobe had increased from 8 to 11 mm in diameter. The
      lesion was diagnosed to be cT1aN0M0 non-small cell lung cancer (NSCLC) and a 3
      port video-assisted thoracic surgery (VATS) anatomic segmentectomy was performed.
      Intraoperative frozen sections revealed a microinvasive adenocarcinoma.
      Systematic lymph node dissection was then carried out. The final pathological
      result showed a pT1aN0M0 (Ia) adenocarcinoma.

PMID- 29221305
TI  - Left upper lobectomy and pulmonary angioplasty by uniportal video-assisted
      thoracic surgery.
AB  - Diego Gonzalez-Rivas and his colleagues performed the first case for pulmonary
      major resection by the uniportal approach in 2010. In the following years, more
      and more expert surgeons developed the uniportal approach and even applied it to
      very complex cases. Many centers have showed that uniportal video-assisted
      thoracic surgery (VATS) lobectomy is a safe and feasible technique. The patient
      presented here is a complex case: The lingular segmental artery was invaded
      seriously by the tumor and it was difficult to divide it freely, and the
      pulmonary artery plasty was needed. Although this condition made the procedure
      some technically challenging, the case was performed successfully without any
      operative complications.

PMID- 29221302
TI  - The Society for Translational Medicine: clinical practice guidelines for
      mechanical ventilation management for patients undergoing lobectomy.
AB  - Patients undergoing lobectomy are at significantly increased risk of lung injury.
      One-lung ventilation is the most commonly used technique to maintain ventilation
      and oxygenation during the operation. It is a challenge to choose an appropriate
      mechanical ventilation strategy to minimize the lung injury and other adverse
      clinical outcomes. In order to understand the available evidence, a systematic
      review was conducted including the following topics: (I) protective ventilation
      (PV); (II) mode of mechanical ventilation [e.g., volume controlled (VCV) versus
      pressure controlled (PCV)]; (III) use of therapeutic hypercapnia; (IV) use of
      alveolar recruitment (open-lung) strategy; (V) pre-and post-operative application
      of positive end expiratory pressure (PEEP); (VI) Inspired Oxygen concentration;
      (VII) Non-intubated thoracoscopic lobectomy; and (VIII) adjuvant pharmacologic
      options. The recommendations of class II are non-intubated thoracoscopic
      lobectomy may be an alternative to conventional one-lung ventilation in selected
      patients. The recommendations of class IIa are: (I) Therapeutic hypercapnia to
      maintain a partial pressure of carbon dioxide at 50-70 mmHg is reasonable for
      patients undergoing pulmonary lobectomy with one-lung ventilation; (II) PV with a
      tidal volume of 6 mL/kg and PEEP of 5 cmH2O are reasonable methods, based on
      current evidence; (III) alveolar recruitment [open lung ventilation (OLV)] may be
      beneficial in patients undergoing lobectomy with one-lung ventilation; (IV) PCV
      is recommended over VCV for patients undergoing lung resection; (V) pre- and post
      operative CPAP can improve short-term oxygenation in patients undergoing
      lobectomy with one-lung ventilation; (VI) controlled mechanical ventilation with
      I:E ratio of 1:1 is reasonable in patients undergoing one-lung ventilation; (VII)
      use of lowest inspired oxygen concentration to maintain satisfactory arterial
      oxygen saturation is reasonable based on physiologic principles; (VIII) Adjuvant
      drugs such as nebulized budesonide, intravenous sivelestat and ulinastatin are
      reasonable and can be used to attenuate inflammatory response.

PMID- 29221306
TI  - Systemic tunnel dissection of mediastinal lymph nodes without clamping via
      uniportal video-assisted thoracoscopic surgery.
AB  - Here we introduce a manual tunnel approach to remove the mediastinal lymph nodes
      and highlight the conception of non-clamping during dissection. We describe two
      cases of pulmonary malignancy performing a strategic lobectomy and systemic
      dissection of mediastinal lymph nodes via single port. The technique of tunnel
      dissection without clamping ensure to satisfy the requirement of oncology and
      clinical criteria. By efficiently specifying surgery procedure and improving
      dissection thoroughness, our approach should be implemented.

PMID- 29221307
TI  - Bronchial interrupted suture anastomosis for video-assisted thoracic surgery
      (VATS) right upper lobe resection.
AB  - A 60 years old man with right upper lobe squamous cell carcinoma was admitted in
      the department of thoracic surgery after receiving two cycles of chemotherapy.
      Chest computed tomography (CT) revealed the mass reduce to 2.0*1.5 cm. No
      contraindications or metastasis was found after routine preoperative examination.
      It took 3 hours to complete this operation. Final pathology stage was T3N0M0,
      stage IIA. This patient discharged on the 7th postoperative day with no
      complications.

PMID- 29221303
TI  - The Society for Translational Medicine: clinical practice guidelines for the
      postoperative management of chest tube for patients undergoing lobectomy.
AB  - The Society for Translational Medicine and The Chinese Society for Thoracic and
      Cardiovascular Surgery conducted a systematic review of the literature in an
      attempt to improve our understanding in the postoperative management of chest
      tubes of patients undergoing pulmonary lobectomy. Recommendations were produced
      and classified based on an internationally accepted GRADE system. The following
      recommendations were extracted in the present review: (I) chest tubes can be
      removed safely with daily pleural fluid of up to 450 mL (non-chylous and non
      sanguinous), which may reduce chest tube duration and hospital length of stay
      (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use
      of PrRP/B <0.5 when evaluating fluid output to determine chest tube removal might
      be beneficial (2B); (III) it is recommended that one chest tube is adequate
      following pulmonary lobectomy, except for hemorrhage and space problems (2A);
      (IV) chest tube clearance by milking and stripping is not recommended after lung
      resection (2B); (V) chest tube suction is not necessary for patients undergoing
      lobectomy after first postoperative day (2A); (VI) regulated chest tube suction [
      11 (-1.08 kPa) to -20 (1.96 kPa) cmH2O depending upon the type of lobectomy] is
      not superior to regulated seal [-2 (0.196 kPa) cmH2O] when electronic drainage
      systems are used after lobectomy by thoracotomy (2B); (VII) chest tube removal
      recommended at the end of expiration and may be slightly superior to removal at
      the end of inspiration (2A); (VIII) electronic drainage systems are recommended
      in the management of chest tube in patients undergoing lobectomy (2B).

PMID- 29221308
TI  - How to manage tumor located between upper division and lingular segment "S3+S4
      segmentectomy and S3b+S4 segmentectomy".
AB  - Segmentectomy is one of the treatment of choice for small-sized non-small cell
      lung cancer (NSCLC). Although simple segmentectomy is feasible even if under
      thoracoscopy, complicated segmentectomy which contains more than two segmental
      plane divisions is difficult especially thoracoscopic surgery. We here present
      the case of totally thoracoscopic segmentectomy between upper division and
      lingular segment. In the first case, the 64-year-old female patient admitted for
      further examination and treatment of left lung ground glass nodule. Tumor located
      between upper division (S3) and lingular (S4) segment was operated by bi
      segmentectomy and intraoperative frozen section pathology showed minimally
      invasive adenocarcinoma. Systematic nodal dissection was followed after retrieval
      of specimens. A3b A3a+c, and A4 was individually divided and followed by division
      of B3 and B4. Finally, intersegmental veins V1+2a and V1+2d was identified
      between segments and V3a+b was divided. In the second case, the 76-year-old
      female patient with left lung nodule between upper division (S3b) and lingular
      (S4) segment was operated by bi-segmentectomy. Since sealing test revealed air
      leakage from resected segmental planes, fibrin glue was applied to stop air
      leakage and direct suturing by 4-0 prolene between S3a+S3c and S5 was performed.
      Target lesion between upper division and lingular segments may be resected safely
      if appropriate demarcation lines are identified regardless of without highly
      sophisticated imaging systems.

PMID- 29221309
TI  - Uniportal video-assisted thoracoscopic right upper posterior segmentectomy with
      systematic mediastinal lymphadenectomy.
AB  - Uniportal video-assisted thoracoscopic surgery (VATS) has now evolved into a
      sophisticated technique that can be used in some of the most complex thoracic
      procedures; however, this approach to segmentectomy is not standardized, and the
      surgical procedure varies between surgeons. Here, we describe the use of our
      uniportal VATS procedure during right upper posterior segmentectomy in a patient
      with a nodule in the right upper lobe. Subsequent mediastinal lymphadenectomy was
      performed. The patient has recovered well after surgery. We believe that
      uniportal VATS segmentectomy is a technically safe and feasible alternative
      approach to conventional thoracoscopic techniques for treating lung cancer.

PMID- 29221310
TI  - Uniportal video-assisted thoracoscopic surgery left upper lobe trisegmentectomy
      using flexible tip 3D video scope.
AB  - A 69-year-old male patient with a history of melanoma and prostate cancer was
      found to have a 2.6 cm PET-avid, slowly enlarging, left upper lobe lung nodule
      that was suspicious for either metastasis or primary lung cancer. Due to the deep
      location of the nodule, a wedge resection was not recommended. A diagnostic and
      therapeutic uniportal video-assisted thoracoscopic surgery (U-VATS) left upper
      lobe trisegmentectomy was performed uneventfully. Final pathology confirmed the
      presence of metastasis from prostate cancer without lymph node involvement. His
      recovery was uneventful and he was discharged two days after surgery. In this
      video, we demonstrate our technique for left upper lobe lingula-sparing lobectomy
      (trisegmentectomy). More importantly, the video demonstrates that a thorough
      lymphadenectomy can be effectively performed during U-VATS lung resections.

PMID- 29221311
TI  - Uniportal video-assisted thoracic surgery lobectomy in a patient with carcinoid
      tumor located at the orifice of the right lower lobe.
AB  - We present here a 47-year old male patient who had a typical carcinoid tumor
      located at the orifice of right lower lobe bronchus underwent uniportal
      thoracoscopic lower lobectomy following bronchoscopic removal of the
      endobronchial tumor. Tumor was seen by bronchoscopy to protrude out from the
      lower lobe into the intermediary bronchus obstructing the lower lobe completely
      and the middle lob partially. However, the origin of the endobronchial tumor was
      in the distal part of the lower lobe bronchus. In this case, open surgery could
      be an alternative to save the middle lobe by incising the lower lobe bronchus to
      pull out the endobronchial tumor first during thoracotomy. The other alternative
      could be a thoracoscopic lower bilobectomy for achieving a curative resection. In
      this patient, we performed sequential approaches at the same session as;
      bronchoscopic removal of the endobronchial tumor first, and then uniportal VATS
      lower lobectomy. Frozen section pathological analyses of bronchial stump of
      resected right lower lobe as well as the postoperative bronchoscopic biopsy
      confirmed a tumor-free margin. Patient was discharged on postoperative day four
      after an uneventful postoperative course.

PMID- 29221312
TI  - Port-access thoracoscopic bisubsegmentectomy of right upper lobe posterior and
      anterior segments.
AB  - A 64-year-old woman was admitted to our hospital with a 16-mm non-solid tumor
      with pure ground-glass nodule (GGN) contents in the posterior segment near the
      anterior segment of her right upper lung lobe that was suspicious of
      adenocarcinoma in situ (AIS). Three-dimensional computed tomography (3DCT)
      simulation was performed to identify the subsegmental artery and vein pre- or
      intra-operatively. Port-access thoracoscopic bisubsegmentectomy of the right
      upper lobe was performed. A frozen section revealed AIS. The tumor size was 13 mm
      and the surgical margin from the tumor edge to cutting line was more than 20 mm.
      The surgical time was 191 minutes and bleeding was 101 mL. The chest tube
      duration was 3 days and the post-operative hospital stay was 6 days.

PMID- 29221313
TI  - Video-assisted thoracoscopic surgery (VATS) lower lobe bisegmentectomy (S7/8) for
      a central pulmonary metastasis.
AB  - Surgery for pulmonary metastasis is performed heterogeneously with regard to
      surgical approach [open vs. video-assisted thoracoscopic surgery (VATS)] and
      resection techniques (e.g., laser enucleation, electro-cautery resection,
      stapling). Complete tumor resection and preservation of lung parenchyma are of
      upmost importance. This is technically challenging, especially for central
      lesions close to vascular and bronchial segmental structures. Thus, simple
      thoracoscopic wedge resections are often not feasible. A VATS lower lobe
      bisegmentectomy (S7/8) was performed on a 62-year-old patient with a suspicious
      pulmonary nodule and a history of hemicolectomy for colorectal carcinoma.
      Different VATS techniques of vessel dissection and parenchymal control were
      applied. VATS anatomic segmental resections represent a helpful tool in surgical
      therapy of central pulmonary metastasis.

PMID- 29221314
TI  - Thoracoscopic left S4a subsegmentectomy.
AB  - A 63-year-old woman who underwent a left hepatic lobectomy for hilar
      cholangiocarcinoma was referred to our department for further management. Chest
      computed tomography showed a lung nodule that was increased in size to 8 mm in
      the S4a. The differential diagnosis was metastasis versus primary lung cancer.
      Thoracoscopic left S4a subsegmentectomy was performed. The operative time was 158
      min. The blood loss was minimal. Air leakage was not observed, and a chest tube
      was removed on POD 1. The patient was discharged home on POD 3. The final
      diagnosis was primary lung cancer (T1aN0M0 stage IA). Surgical margin was 2.0 cm.

PMID- 29221315
TI  - Four arm robotic-assisted pulmonary resection-right upper lobectomy: how to do
      it.
AB  - Numerous published articles have shown the safety and efficacy of robotic lung
      resection, including lobectomy. Several techniques have been described by
      different authors to perform a robot assisted lung lobectomy. We adopted four
      arms robotic procedure. We usually perform three ports (10-15 mm) and an anterior
      3 to 4 cm utility incision. This technique allows to safely proceed with an
      anterior to posterior approach to the hilum. In this study, we present in clear
      and sequential steps, the procedure to perform a right upper lobectomy for early
      stage lung cancer. We also supply a high-quality video, operative tips and a
      preference cards.

PMID- 29221316
TI  - Recent advances in the management of pulmonary tuberculoma with focus on the use
      of tubeless video-assisted thoracoscopic surgery.
AB  - Pulmonary tuberculoma are benign solitary pulmonary nodules representing up to
      25% of all resected solitary pulmonary nodules. However, the differentiation
      between pulmonary tuberculoma and lung cancer, as well as between active
      tuberculoma and inactive tuberculoma remains a clinical challenge. The present
      review summarizes the recent advances in the management of pulmonary tuberculoma,
      including radiological findings, the response to anti-tuberculosis treatment and
      surgical treatments. Application of the novel tubeless video-assisted
      thoracoscopic surgery (VATS) technique in both the diagnosis and treatment of
      pulmonary tuberculoma has been found to be safe and feasible and leads to less
      surgical trauma, which results in reduced length of hospitalization and better
      post-operative quality of life.

PMID- 29221317
TI  - Cystic tumor of the atrioventricular node: a review of the literature.
AB  - Primary cardiac tumors are uncommon clinical entities with an incidence of
      0.0017% to 0.03% of all autopsies. Cystic tumor of the atrioventricular (AV)
      node, also known as mesothelioma of the AV node, is a benign congenital tumor
      that is located in the triangle of Koch in the AV nodal region of the atrial
      septum of the heart. It comprises of 2.7% of cardiac tumors and is the most
      common primary cardiac tumor causing sudden death. We herein review the etiology,
      presentation, differential diagnosis, diagnosis, management, surgical approaches
      and outcomes of this rare tumor.

PMID- 29221319
TI  - Lung transplantation in elderly patients.
AB  - Consensus statements on the selection of lung transplant candidates have
      consistently identified older age as a relative contraindication to
      transplantation. A combination of population-level demographic changes, revision
      of the lung allocation score (LAS), and clearer data on outcomes in elderly
      transplant recipients has, however, driven a steady increase in the threshold at
      which age is taken into consideration. This article reviews the current state of
      lung transplantation in elderly patients with an emphasis on the factors that
      have increased lung transplantation in older age groups, their expected outcomes
      including survival and health-related quality of life, and the factors that go in
      to appropriate candidate and procedure selection in this population.

PMID- 29221320
TI  - Bridging to lung transplantation with extracorporeal circulatory support: when or
      when not?
AB  - Patients with end-stage lung disease who are candidates for lung transplantation
      may acutely decompensate before a donor organ becomes available. In this
      scenario, extracorporeal life support (ECLS) may be considered as a bridge to
      transplant or as a bridge to decision. In the current chapter, we review the
      indications, techniques, and outcomes for bridging to lung transplantation with
      ECLS.

PMID- 29221318
TI  - Lung densitometry: why, how and when.
AB  - Lung densitometry assesses with computed tomography (CT) the X-ray attenuation of
      the pulmonary tissue which reflects both the degree of inflation and the
      structural lung abnormalities implying decreased attenuation, as in emphysema and
      cystic diseases, or increased attenuation, as in fibrosis. Five reasons justify
      replacement with lung densitometry of semi-quantitative visual scales used to
      measure extent and severity of diffuse lung diseases: (I) improved
      reproducibility; (II) complete vs. discrete assessment of the lung tissue; (III)
      shorter computation times; (IV) better correlation with pathology quantification
      of pulmonary emphysema; (V) better or equal correlation with pulmonary function
      tests (PFT). Commercially and open platform software are available for lung
      densitometry. It requires attention to technical and methodological issues
      including CT scanner calibration, radiation dose, and selection of thickness and
      filter to be applied to sections reconstructed from whole-lung CT acquisition.
      Critical is also the lung volume reached by the subject at scanning that can be
      measured in post-processing and represent valuable information per se. The
      measurements of lung density include mean and standard deviation, relative area
      (RA) at -970, -960 or -950 Hounsfield units (HU) and 1st and 15th percentile for
      emphysema in inspiratory scans, and RA at -856 HU for air trapping in expiratory
      scans. Kurtosis and skewness are used for evaluating pulmonary fibrosis in
      inspiratory scans. The main indication for lung densitometry is assessment of
      emphysema component in the single patient with chronic obstructive pulmonary
      diseases (COPD). Additional emerging applications include the evaluation of air
      trapping in COPD patients and in subjects at risk of emphysema and the staging in
      patients with lymphangioleiomyomatosis (LAM) and with pulmonary fibrosis. It has
      also been applied to assess prevalence of smoking-related emphysema and to
      monitor progression of smoking-related emphysema, alpha1 antitrypsin deficiency
      emphysema, and pulmonary fibrosis. Finally, it is recommended as end-point in
      pharmacological trials of emphysema and lung fibrosis.

PMID- 29221321
TI  - Living-related lung transplantation.
AB  - Living-donor lobar lung transplantation (LDLLT) was developed to deal with the
      severe shortage of brain dead door for patients who would not survive the long
      waiting period. In standard LDLLT, right and left lower lobes removed from two
      healthy donors are implanted into a recipient after right and left
      pneumonectomies using cardiopulmonary bypass (CPB). The number of LDLLT has
      decreased in the USA due to the recent change in allocation system for cadaveric
      donor lungs. For the past several years, most of the reports on LDLLT have been
      from Japan, where the average waiting time for a cadaveric lung is exceeding 800
      days. LDLLT has been performed both for adult and pediatric patients suffering
      from various end-stage lung diseases including restrictive, obstructive, vascular
      and infectious lung diseases. Since only two lobes are implanted, size matching
      is a very important issue. Functional size matching by measuring donor pulmonary
      function and anatomical size matching by three-dimensional computed tomography
      (3D-CT) volumetry are very useful. For oversize graft, we have employed several
      techniques, including single lobe transplantation, delayed chest closure,
      downsizing the graft, and middle lobe transplantation. In cases of undersize
      mismatch, native upper lobe sparing transplant or right-left inverted transplant
      was performed. The 5-, 10- and 15-year survivals were 80.8%, 72.6% and 61.7%,
      respectively. There was no difference in survival between standard LDLLT and non
      standard LDLLT such as single, sparing and inverted transplant. All donors have
      been discharged without any restrictions. LDLLT is a viable option for very ill
      patients who would not survive a long waiting time for cadaveric lungs. We have
      successfully developed various surgical techniques to overcome size mismatching
      with favorable outcome.

PMID- 29221323
TI  - Management of non-small cell lung cancer with EGFR mutation: the role of
      radiotherapy in the era of tyrosine kinase inhibitor therapy-opportunities and
      challenges.
AB  - In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was
      greatly promoted by the discovery of oncogenic drivers and the development of
      targeted therapies specific for these drivers. Somatic mutations in epidermal
      growth factor receptor (EGFR) are the most common type in patients with NSCLC.
      Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively
      high response rate and long duration with acceptable toxicity profile. Also, the
      life expectancy in patients with active EGFR mutation has been significantly
      prolonged than the past. Additionally, evolution of advanced imaging and
      radiation techniques has expanded the indications for radiotherapy in complex
      clinical situation. All of those factors contributed to the widely use of
      radiotherapy for advanced NSCLC treated with TKI therapy. In this review, we will
      discuss how to integrate radiotherapy into the comprehensive treatment of
      patients with TKI therapy in order to maximize the therapeutics effect.

PMID- 29221322
TI  - Recipient selection process and listing for lung transplantation.
AB  - Lung transplantation remains the ultimate treatment option for selected patients
      with end-stage (cardio) pulmonary disease. Given the current organ shortage, it
      is without any doubt that careful selection of potential transplant candidates is
      essential as this may greatly influence survival after the procedure. In this
      paper, we will review the current guidelines for referral and listing of lung
      transplant candidates in general, and in more depth for the specific underlying
      diseases. Needless to state that these are not absolute guidelines, and that
      decisions depend upon center's activity, waiting list, etc. Therefore, every
      patient should be discussed with the transplant center before any definite
      decision is made to accept or decline a patient for lung transplantation.

PMID- 29221324
TI  - The role of sympathectomy in long QT syndrome.
AB  - Long QT syndrome (LQTS) is an uncommon and potentially fatal cardiac
      channelopathy. Treatment options can be medical with beta-blockers or surgical
      with implantable cardioverter defibrillator (ICD) implantations and left cardiac
      sympathetic denervation (LCSD). Purpose of this paper is through a literature
      review to identify the management algorithm and the role of sympathectomy in
      LQTS.

PMID- 29221326
TI  - Introduction to JTD Air Pollution Section.

PMID- 29221325
TI  - Foreign body aspiration in adult airways: therapeutic approach.
AB  - Tracheobronchial foreign body (FB) aspiration is an uncommon but potentially life
      threatening event in adults. Symptoms typically consist of a choking event
      followed by cough and dyspnea, however, these findings are inconsistent and
      symptoms may mimic more chronic lung diseases such as asthma or chronic
      obstructive pulmonary disease. Chest radiography and computed tomography can
      provide information regarding the location and characteristics of foreign bodies
      and aid in diagnosis. Bronchoscopy remains the gold standard for diagnosis and
      management of FB aspiration. The authors describe the typical clinical
      presentation, diagnostic evaluation, and bronchoscopic management of foreign
      bodies in adult airways with a focus on bronchoscopic techniques and potential
      complications of FB extraction.

PMID- 29221327
TI  - War-time asthma: lessons from Syria.

PMID- 29221328
TI  - Uncontrolled and under-diagnosed asthma in a Damascus shelter during the Syrian
      crisis.
AB  - Background: Studies have shown that poor shelter or dwelling conditions may lead
      to deteriorations in health. Those with asthma may be more susceptible to
      compromised living conditions and stress leading to a higher risk of asthma
      exacerbations. To describe the asthma control and quality of life of individuals
      with diagnosed asthma living in a shelter in Damascus, Syria and estimate the
      prevalence of respiratory symptoms in shelter dwellers without diagnosed asthma.
      Methods: In this cross-sectional study, all individuals 5 years and older living
      in Al-Herjalleh shelter with diagnosed asthma were recruited to complete a
      questionnaire, which included items related to their respiratory symptoms, asthma
      exacerbations, exposure to asthma triggers, medication use, and health-related
      quality of life before and since entering the shelter. A representative sample of
      shelter dwellers without diagnosed asthma also completed a questionnaire to
      establish their demographics, respiratory symptoms, environment and chronic
      disease co-morbidities, in order to identify factors associated with under
      diagnosed asthma. All participants underwent spirometry to measure their lung
      function. Descriptive statistics were calculated, and chi-square tests and
      Student's t-tests were used to compare individuals with asthma before and since
      entering the shelter, as well as to compare those with under-diagnosed asthma and
      individuals without asthma. Results: The prevalence of asthma at the Al-Herjalleh
      shelter in those aged 5 years and older was approximately 8.5%. Nearly 70% of the
      asthma group felt their asthma had worsened since entering the shelter, and there
      was a significant drop in the proportion of individuals using inhaled
      corticosteroids (ICS), with only 4.3% using daily ICS in the shelter (P<0.0001).
      The proportion of individuals experiencing a severe asthma attack did not change
      after entering the shelter (P=0.97), but almost all individuals with asthma
      (94.4%) reported worsening in their health-related quality of life. In the non
      asthma group, 44.2% of participants reported episodes of wheezing, coughing and
      breathlessness at night, consistent with under-diagnosed asthma. A higher
      proportion of those with under-diagnosed asthma had allergic rhinitis (57.1%),
      symptoms of post-traumatic stress disorder (PTSD) (35.1%), and abnormal
      spirometry (60.0%), compared to those without asthma. Conclusions: The findings
      of our study highlight the need for asthma programs in Syrian shelters as
      significant gaps exist in both the screening and management of chronic
      respiratory diseases to minimize asthma deterioration in Syrian shelter dwellers.

PMID- 29221329
TI  - Inter-hospital transports on extracorporeal membrane oxygenation in different
      health-care systems.
AB  - The feasibility and the recognition of the possibility to transport patients on
      extracorporeal membrane oxygenation (ECMO) aroused in the 1970s. The number of
      transporting facilities worldwide was less than 20 in the beginning of the second
      Millennium. In 2009 the H1N1 pandemic and a publication showing survival benefit
      for adult patients transported to a hospital with ECMO resource increased both
      awareness and interest for ECMO treatment. The number of transport organizations
      increased rapidly. As of today, the number of transport organizations increases
      world-wide, though some centers where ECMO is an established treatment report
      decreasing numbers of transports. Since the introduction of the more user
      friendly equipment (ECMO-2 era) increasing numbers of low-volume ECMO centers
      perform these complex treatments. This overview is based on the current
      literature, personal experience in the field, and information from the authors'
      network on the organization of ECMO transport systems in different settings of
      health care around the globe. Registry data since the entry into ECMO-2 shows
      that the number of ECMO treatments matter. The more treatments performed at a
      given center the better the patient outcome, and the better these resources are
      spent for the population served. A Hub-and-Spoke model for national or regional
      organization for respiratory ECMO (rECMO) should be advocated where central high
      volume ECMO center (Hub) serves a population of 10 to 15 million. Peripheral
      units (Spokes) play an important part in emergency cannulations keeping the
      patient on ECMO support till a mobile ECMO team retrieves the patient. This ECMO
      team is preferably organized from the Hub and brings competencies for assessment
      and decision to initiate ECMO treatment bedside at any hospital, for cannulation,
      and a safe transport to any destination. To conclude, most ECMO transport
      organizations are reflections of the health care paradigm within which they act.
      Most transport organizations are established by the staff within who recognize
      the need. The legal space seems open in most countries; anyone may set up a
      transport organization anywhere. Quality follow-up varies. Some keep track of
      adverse events and report whereas most transport entities do not seem to
      prioritize this. There is no international body for ECMO transports. Such would
      be the key for definitions, support, networking, and a registry that successively
      would increase knowledge concerning adverse events, morbidity and mortality.

PMID- 29221330
TI  - Lung transplantation in the most critically-III: forging ahead.
AB  - Lung transplantation is the gold standard therapy for patients with end-stage
      lung disease. The use of the lung allocation score (LAS) has permitted improved
      allocation of scarce pulmonary allografts. Recently, Crawford et al. examined the
      experience in the United States in lung transplantation in candidates with the
      highest LAS, demonstrating that outcomes for candidates with the highest LAS
      scores have improved significantly. This editorial places these data in the
      broader context of thoracic transplantation, and highlights the critical need for
      ongoing examination of this critically-ill patient population.

PMID- 29221331
TI  - Five reasons for caution in advocating low-dose computerized tomographic lung
      cancer screening.
AB  - The 53.5K-person, low-dose computerized tomographic (LDCT), National Lung Cancer
      Screening Trial (NLST) achieved a 20% reduction in lung cancer mortality and a
      6.7% reduction in all-cause mortality at 6.5-year median follow-up. Failure of
      European LDCT trials employing null (i.e., unscreened) controls to reproduce this
      benefit compels caution in adopting a policy of population screening. Additional
      concerns merit attention: surgical mortality is not trivial; overdiagnosis is
      substantial; disease-free life expectancy and quality of life are markedly
      diminished by loss of pulmonary reserve; the combination of overdiagnosis and
      diminished disease-free life expectancy is pernicious.

PMID- 29221332
TI  - Surgery for a large tracheoesophageal fistula using extracorporeal membrane
      oxygenation.
AB  - We report a patient with a giant tracheoesophageal fistula (TEF) planned for
      reconstructive surgery. Because mechanical ventilation in any form was
      technically impossible, we successfully used veno-venous extracorporeal membrane
      oxygenation (VV-ECMO) without the need for mechanical ventilation.

PMID- 29221333
TI  - Successful treatment of a ruptured left internal mammary artery aneurysm with a
      delayed diagnosis of type I neurofibromatosis.
AB  - Neurofibromatosis type I (NF-1) induced vasculopathy is rare but catastrophic
      complication after aneurysmal rupture. We present the case of a 55-year-old
      female who developed hypovolemic shock because of left internal mammary artery
      (IMA) pseudoaneurysm rupture associated with NF-1. Even she was not detected NF-1
      at the time of arrival in emergency room. We decided to perform percutaneous
      embolization instead of surgical approach. In this case, after intervention, the
      ruptured left IMA aneurysm was well treated. After 10 days, the patient
      discharged without any complications.

PMID- 29221334
TI  - Minimally invasive, multi-disciplinary approach for surgical management of a
      mediastinal congenital bronchogenic cyst in a 6-month-old infant.
AB  - We present a case of prenatal diagnosis of a mediastinal cyst by ultrasound,
      confirmed during infancy through computed tomography (CT) and magnetic resonance
      imaging (MRI). A 6-month-old male infant was admitted to the hospital. A mid
      mediastinal cyst was detected through a province-wide fetal ultrasonography
      screening program. During the infancy stage, the CT scan and the MRI confirmed
      the finding of a mediastinal cyst. Based on the findings on prenatal
      ultrasonography and postnatal imaging studies (CT, MRI), a benign mediastinal
      cyst was suspected. The cyst was below the tracheal carina, and the patient
      developed symptoms of respiratory distress. Owing to the enlargement trend of the
      cyst, the respiratory distress it has caused, and the anxiety it caused to the
      patient's family, a multi-disciplinary conference reached the consensus that
      surgical resection is the treatment of choice and a carina-approach mediastinal
      lesion resection via video-assisted thoracoscopic surgery (VATS) was performed.
      The cyst was removed successfully. Although this report is of a single case and
      follow-up duration is not long enough, we nevertheless make the first move to
      improve the pattern to a feasible, reliable, and efficient one, which could be
      used to treat similar patients.

PMID- 29221335
TI  - Chylothorax after mediastinal ganglioneuroma resection treated with fibrin
      sealant patch: a case report.
AB  - Chylothorax is a severe condition resulting from the accumulation of chyle into
      the pleural space. We report the treatment of postoperative chylothorax after
      resection of mediastinal ganglioneuroma in a 17-year-old boy. Since conservative
      measures were not effective, we performed direct ligation of lymphatic vessels
      and pleurodesis. At subsequent surgical re-exploration for persisting
      chylothorax, accurate inspection of pleural cavity revealed residual chyle
      leakage. Fibrin sealant patches (TachoSil(r)) were placed over the source of leak
      with complete resolution of chylous effusion. To our knowledge, this is the first
      report of postoperative chylothorax successfully treated by the use of a fibrin
      sealant patch.

PMID- 29221336
TI  - Hemangiopericytoma 11 years later: delayed recurrence of a rare soft tissue
      sarcoma.
AB  - Hemangiopericytomas (HPCs) are uncommon tumours. We present the case of a 41-year
      old female with multiple resections at different sites over the course of 11
      years. The approach considerations, as well as treatment options and prognosis
      are discussed. A 41-year-old female with two previous resections for intracranial
      meningeal HPC in 2004 and 2008, as well as adjuvant radiotherapy, presented in
      2015 with left intrathoracic and left hip recurrence confirmed by positron
      emission tomography/computed tomography (PET/CT). She underwent left proximal
      femur resection/reconstruction and video-assisted thoracoscopic surgery (VATS)
      resection of the intrathoracic tumour was attempted. She was discharged home on
      her 4th post-operative day with minimal pain. There were no neurosensory or motor
      deficits. Any patient who has been diagnosed with HPC in the past who develops
      new symptoms should be worked up for recurrence, regardless of the length of
      disease-free interval, as our case study suggested. There has yet to be a
      standardized follow-up regime due to the rarity of these tumours. HPC remains a
      rare soft tissue sarcoma with high recurrence rate. Planned VATS evaluation and
      resection is possible provided complete resection with clear surgical margins can
      be achieved, as clear surgical margins offer the best chance of survival.

PMID- 29221337
TI  - A case report of giant esophageal neurofibroma.
AB  - Esophageal neurofibroma is a rare type of benign esophageal tumor. We presented a
      case of a 63-year-old man with a 12-cm diameter upper-thoracic esophageal
      submucosal tumor. Surgery of a thoracotomy was performed to remove the lesion.
      The postoperative course was uneventful and the patient was discharged on the
      postoperative day 10. Immunohistochemical staining confirmed the diagnosis of
      esophageal neurofibroma.

PMID- 29221338
TI  - The new transbronchial diagnostic approach for the metastatic lung tumor from
      renal cell carcinoma-a case report.
AB  - Endobronchial ultrasound-guided needle aspiration (EBUS-TBNA) is a well
      established procedure with high diagnostic yield and safety. However, the
      standard 22 gauge needles sometimes cause major bleeding particularly in
      hypervascular tumors like metastatic lung tumors from renal cell carcinoma (RCC).
      The 25 gauge needles are already introduced to endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA), and are considered as one of the standard devices
      due to their comparable diagnostic outcome, lower complication risk, and the
      better manipulability. Recently, the new 25 gauge needles have been applied to
      EBUS-TBNA. In present case, we were able to obtain a definitive diagnosis of the
      metastatic RCC by EBUS-TBNA using the 25 gauge needle. The new thin needle might
      be a better option for hypervascular tumors of the lung.

PMID- 29221339
TI  - Laparoscopic repair of a peritoneopericardial diaphragmatic hernia after a
      convergent procedure for the treatment of atrial fibrillation.
AB  - Peritoneopericardial diaphragmatic hernia is a rare entity involving herniation
      of abdominal viscera through the diaphragm into the pericardial sac. It is most
      often seen after blunt abdominal trauma, but can occur following any trans
      diaphragmatic intervention. We report on a 56-year-old female with
      peritoneopericardial diaphragmatic hernia secondary to a convergent procedure for
      the treatment of atrial fibrillation, who underwent a laparoscopic repair. An
      anterior abdominal wall laparoscopic approach was employed. Transverse colon and
      greater omentum were within the hernia sac. The defect measuring 3 cm * 3 cm was
      repaired using a composite hernia mesh. The total operative time was 78 minutes.
      No intra-operative and no post-operative complications were observed. Patient
      remained asymptomatic at a 6-month follow-up. Laparoscopic mesh repair of
      peritoneopericardial diaphragmatic hernia is safe, feasible and is the procedure
      of choice for treating these complex hernias.

PMID- 29221340
TI  - Sudden hypotension occurring after 4 days of left-sided central catheter
      placement.
AB  - Central venous catheters (CVCs) have an important role in the management of
      critically ill patients. In contrast to the immediate complications after CVC
      insertion, the late complications were difficult to be noticed without high
      suspicion despite their life-threatening outcome. We report a rare but fatal
      delayed vascular perforation occurring after 4 days of left-sided hemodialysis
      catheter insertion. A 74-year-old male with septic shock was treated with
      continuous renal replacement therapy (CRRT) and recovered smoothly during
      hospitalization. Refractory hypotension occurred abruptly on the fourth hospital
      day. Chest X-ray and computed tomography revealed that the catheter tip
      perforated the innominate vein and located the mediastinum. He finally died
      despite the emergent radiologic intervention.

PMID- 29221341
TI  - Atypical carcinoid localized at the bronchus accompanied by diffuse idiopathic
      pulmonary neuroendocrine cell hyperplasia in the distal lung: a rare case report.
AB  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is
      hyperplasia of noninvasive neuroendocrine cells originating from Kultchitsky
      cells. This is a rare pathological condition, suspected to be a precursor lesion
      of carcinoid, together with tumorlet. In the WHO histological classification (4th
      edition) revised in 2015, DIPNECH was added to the category that includes
      neuroendocrine tumors. Our patient was a 77-year-old woman who initially visited
      another doctor because of coughing. Chest CT revealed a mass occluding the right
      intermediate bronchial trunk, and bronchial carcinoid was suspected from biopsy
      findings, leading to referral of this patient to our department. The tumor was
      excised under a rigid bronchoscope for the purpose of making a definitive
      histological diagnosis and determining the extent of spread. The stalk portion of
      the tumor extended from the bifurcation of the middle and lower lobe bronchi in
      the membranous part of the intermediate trunk to the central side. The airway
      appeared to be almost completely occluded under bronchoscopy, but aeration from
      the periphery was maintained. Histopathologically, there was hyperplasia of oval
      atypical cells with relatively poor cytoplasm beneath the bronchial mucosa on HE
      staining, suggesting neuroendocrine tumor. Immunostaining revealed that these
      cells were positive for CD56, chromogranin A, and synaptophysin, and that there
      was moderate mitosis, leading to a diagnosis of atypical carcinoid. At a later
      date, radical surgery comprised of right pulmonary middle and lower lobectomy and
      lymph node dissection was performed. The final histopathological diagnosis was
      atypical carcinoid of the bronchus (pT1aN0M0, stage IA). There were multiple
      aggregations of atypical cells, measuring approximately 1-3 mm, along the airway
      around the bronchioles in the excised lung, indicating concomitant DIPNECH. The
      patient currently has no evidence of either recurrence or metastasis at 12 months
      after surgery, but we will continue meticulous follow-up.

PMID- 29221342
TI  - Tuberculous tracheobronchial stenosis: avoiding resection-when less is more.
AB  - A case of tracheobronchial stenosis due to tuberculosis in a young woman is
      presented. Compromised pulmonary function due to near-total obstruction of the
      proximal left main bronchus was diagnosed. Treatment options included surgical
      resection, endobronchial dilation or stenting, and argon photocoagulation. An
      approach was chosen to address symptoms without aggressive resection or
      commitment to stenting. She remains monitored and, while possibly committed to
      future intervention, no bridges have been burned with respect to more definitive
      and invasive therapies. We propose this "less is more" initial approach in all
      patients when possible. Reserving the more aggressive alternatives for high-risk
      surgical candidates and those that have been unresponsive to lesser procedures.

PMID- 29221343
TI  - Adult-onset Langerhans cell histiocytosis of the sternum.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease with uncertain etiology
      that is more prevalent in children. LCH typically invades skeletal systems, but
      in rare cases, it has been reported in the ribs or sternum. Optimal treatment
      choices for single-site, skeletal LCH are still undefined. We report a case of
      adult-onset LCH of the sternum. The range of surrounding soft tissue invasion was
      confirmed by three-dimensional fusion and reconstruction of chest computed
      tomography and magnetic resonance images. Our patient was successfully treated by
      local surgical curettage and adjuvant radiation therapy. We concluded that
      postoperative adjuvant radiation therapy may be advantageous for single-site LCH
      of bones with soft tissue invasion.

PMID- 29221344
TI  - Endoscopic diverticulotomy with a stapler can be an effective and safe treatment
      for Killian-Jamieson diverticulum.
AB  - Killian-Jamieson diverticulum (KJD) is a rarely encountered esophageal
      diverticulum which attributes to several symptoms. Clinically, KJD should be
      differentiated from the most common type of esophageal herniation, i.e., Zenker's
      diverticulum (ZD). The two diverticula may present in a similar fashion, and
      treatments have evolved from transcervical to a minimally invasive endoscopic
      approach in recent years. We present a case of an 88-year-old male with
      symptomatic esophageal diverticulum. Barium swallow esophagogram and flexible
      esophagoscopy demonstrated a large KJD with food debris retention. Endoscopic
      diverticulotomy using a stapler was performed successfully without injury to the
      recurrent laryngeal nerve (RLN). A literature review and discussion concerning
      etiology, clinical presentations, and radiographic characteristics of KJD was
      conducted, and comparison between open and endoscopic method for esophageal
      diverticulum was also carried out.

PMID- 29221345
TI  - A rare mixed breast cancer of intraductal and solid papillary with tubular
      carcinoma histotypes in a young woman.
AB  - Mixed breast cancer, especially of uncommon breast cancer histotypes, is rare,
      limiting our understanding of the disease and influencing diagnostic and
      management outcomes. We report a case of mixed breast cancer, with features of
      intraductal and solid papillary and tubular carcinomas, which appeared in a young
      patient. Physical examination, ultrasonography, molybdenum target mammography,
      and histopathology were performed for a definitive diagnosis. Tumor resection
      followed by radiotherapy and adjuvant chemotherapy was selected as the
      therapeutic strategy, and the patient was followed up thrice post treatment. We
      discuss the detailed diagnosis, treatment, and follow-up, together with a
      literature review of mixed breast cancer, to help optimize clinical management of
      mixed breast cancer.

PMID- 29221346
TI  - Highlighted version successful resection of a tracheal metastasis of rectal
      cancer: a case report.
AB  - A tracheal metastasis (TM) from non-pulmonary malignancy is extremely rare, and
      there are very few reports regarding TM. Here, we report a case of the successful
      tracheal resection of TM of colorectal cancer. A 36-year-old man underwent a
      surgical resection for the rectal cancer. Approximately 5 years after the
      surgical resection of the primary rectal cancer, an isolated TM was identified.
      The patient was successfully treated with a tracheal resection. In conclusion,
      the current case suggested that the best treatment of the isolated TM might be a
      surgical resection.

PMID- 29221347
TI  - Safe administration of intrapleural alteplase during pregnancy.
AB  - Instillation of intrapleural (IP) fibrinolytics has been used in patients with
      complicated parapneumonic pleural effusions to improve fluid drainage and
      decrease the need for surgical intervention. However, clinical trials have not
      included certain special populations such as pregnant females and there are
      currently no published case reports of this practice in this group. We describe
      the case of a 35-year-old female, G2P1 at 32 weeks of gestation, with a
      complicated pleural effusion due to influenza pneumonia with superimposed
      bacterial pneumonia. Her parapneumonic pleural effusion was successfully treated
      with intercostal tube drainage and IP alteplase [tissue plasminogen activator
      (tPA)] administration and systemic antibiotics with no harm to her or her fetus,
      sparing this patient from more invasive surgical procedures. This is the first
      reported case of successful IP tPA administration for a complicated parapneumonic
      pleural effusion in a pregnant patient.

PMID- 29221348
TI  - Lung metastases in an atypical type A thymoma variant.
AB  - A 35-year-old woman had undergone extensive thymothymectomy for type A thymoma
      several years ago. However, two small lung nodules were found 4 and 5 years after
      surgery. After a partial lung resection to remove these nodules, pathology
      revealed that they were metastases of the type A thymoma. A pathological re
      evaluation confirmed that the primary tumor had in fact been an atypical type A
      thymoma variant, a subset added to the WHO classification in 2015. Pathology
      should be re-evaluated in all patients diagnosed with type A thymoma before 2015
      since they may have the more aggressive atypical type A thymoma variant.

PMID- 29221349
TI  - AB thymoma with atypical type A component with delayed multiple lung and brain
      metastases.
AB  - An atypical type A thymoma is a newly added entity to the last World Health
      Organization (WHO) histological classification [2015] of uncertain prognosis. The
      conventional type A and AB thymomas are usually locally aggressive neoplasms that
      rarely metastasize with distant metastases to the central nervous system (CNS)
      occurring extremely exceptionally. We present a history of a woman with a
      mediastinal tumor originally considered to be a Masaoka-Koga stage II "mixed
      thymoma with well-differentiated thymic carcinoma component" according to the
      historic Muller-Hermelink nomenclature. By applying the criteria of the new WHO
      classification the tumor should be reclassified as an AB thymoma with an atypical
      A component. The patient developed metastases to the lung and brain 10 and 15
      years after the original diagnosis, respectively. All metastases morphologically
      corresponded to an atypical A component of primary thymoma. Molecular study
      revealed GTF2I mutations in the primary and one of the metastatic tumors. To our
      knowledge, this is the first description of a GTF2I mutation in AB thymoma with
      atypical A component and its metastases. The presented case highlights the
      necessity of an accurate microscopic search for atypical areas in A or AB
      thymomas because of their potentially negative impact on prognosis.

PMID- 29221352
TI  - Professor Clemens Aigner: the development and the future of lung surgery.

PMID- 29221351
TI  - Extracorporeal membrane oxygenation system as a bridge to reparative surgery in
      ventricular septal defect complicating acute inferoposterior myocardial
      infarction.
AB  - Post-infarction ventricular septal defect (VSD) is a rare but potentially lethal
      complication of acute myocardial infarction. Medical management is usually
      futile, so definitive surgery remains the treatment of choice but the risk
      surgery is very high and the optimal timing for surgery is still under debate. A
      55-year-old man with no previous medical history attended the emergency-room for
      12 h evolution of oppressive chest pain and strong anginal pain 7 days ago. On
      physical examination, blood pressure was 96/70 mmHg, pansystolic murmur over left
      sternal border without pulmonary crackles. An electrocardiogram revealed sinus
      rhythm 110 bpm, elevation ST and Q in inferior-posterior leads. Transthoracic
      echocardiogram showed inferoposterior akinesia, posterior-basal septal rupture (2
      cm * 2 cm) with left-right shunt. Suspecting VSD in inferior-posterior acute
      myocardial infarction evolved, we performed emergency coronarography with 3
      vessels disease and complete subacute occlusion of the mid segment of the right
      coronary artery. Left ventriculography demonstrated shunting of contrast from the
      left ventricule to the right ventricule. He was rejected for heart
      transplantation because of his age. Considering the high surgical risk to early
      surgery and his hemodynamic and clinical stability, delayed surgical treatment is
      decided, and 4 days after admission the patient suffered hemodynamic instability
      so venoarterial extracorporeal membrane oxygenation system (ECMO) is implanted as
      a bridge to reparative surgery. The 9th day after admission double bypass,
      interventricular defect repair with pericardial two-patch exclusion technique,
      and ECMO decannulation were performed. The patient's postoperative course was
      free of complications and was discharged 10 days post VSD repair surgery. Follow
      up 3-month later revealed the patient to be in good functional status and good
      image outcome with intact interventricular septal patch without shunt. ECMO as a
      bridge to reparative surgery in postinfarction VSD is an adequate option to
      stabilize patients until surgery.

PMID- 29221350
TI  - Glomus tumors of the trachea: 2 case reports and a review of the literature.
AB  - Glomus tumors (GTs) of the trachea are very rare neoplasms that usually arise
      from the distal portion of the respiratory tree. The origin of these tumors is
      modified smooth muscle cells of glomus bodies. In this study, we describe two
      cases of GT of the trachea, as well as the histologic features of these tumors
      and their treatments. One tumor was diagnosed via bronchoscopic biopsy, and the
      other tumor was diagnosed via surgery. Clinical follow-up showed that the two
      patients are alive and well after 8 and 15 months post-treatment, respectively.
      We also review the literature regarding GTs and discuss the clinical
      presentation, histologic features, differential diagnosis, treatment and
      prognosis of these tumors.

PMID- 29221353
TI  - Professor Yin-Kai Chao: art of surgery-the journey of a thoracic surgeon.

PMID- 29221354
TI  - Dr. Masaki Hashimoto: clinical impact of circulating tumor cell in metastatic
      colorectal cancer patients who underwent pulmonary metastasectomy.

PMID- 29221355
TI  - Professor Bruce W. Lytle: let the talented people exhibit their ideas without
      inhibiting them, taking the advantages of the people around you-the key for
      collaboration.

PMID- 29221356
TI  - Prof. John Elefteriades: being alert to everything a patient teaches you.

PMID- 29221357
TI  - Professor Joshua Sonett: to make lung donors more available in the US.

PMID- 29221359
TI  - Thoracic surgeon Lijie Tan in Shanghai Zhongshan Hospital: discussion on the self
      cultivation of a thoracic surgeon.

PMID- 29221358
TI  - Prof. David Watson: new things are not always better.

PMID- 29221360
TI  - Prof. Christopher W. Seder: "Cooperation with the STS database: where do we go
      next?"

PMID- 29221361
TI  - Prof. Jaroslaw Kuzdzal: education on thoracic surgery should include more global
      aspects.

PMID- 29221362
TI  - Comparison of the yield of 19-G eXcelon core needle to a 21-G EBUS needle during
      endobronchial ultrasound guided transbronchial needle aspiration of mediastinal
      lymph nodes for the detection of granulomas in cases of suspected sarcoidosis.

PMID- 29221363
TI  - Sleep disordered breathing and post-cardiac surgery atrial fibrillation.

PMID- 29221364
TI  - Navigation-assisted bronchoscopy for ground-glass opacity lesions.

PMID- 29221365
TI  - Morphine in acute heart failure: good in relieving symptoms, bad in improving
      outcomes.

PMID- 29221366
TI  - PET scan avidity and its role in surgical resection for IIIa N2 disease.

PMID- 29221367
TI  - Target blood pressure in high risk cardiovascular patients.

PMID- 29221368
TI  - Recognizing the strange: experience of the ESTS-AME clinical fellowship in
      Beijing and Guangzhou.

PMID- 29221369
TI  - Controversy and perspective in the management of marginally operable stage IIIA
      non-small cell lung cancer: response to Editorial by Charlotte Billiet and Dirk
      De Ruysscher and Editorial by Dr. Wanpu Yan and Dr. David R. Jones.

PMID- 29221370
TI  - Symptom-based treatment with Traditional Chinese Medicine in bronchiectasis
      patients with hemoptysis.

PMID- 29221371
TI  - Two-Step Nanoscale Approach for Well-Defined Complex Alkanethiol Films on Au
      Surfaces.
AB  - Controlling the molecular organization of organic self-assembled monolayers (SAM)
      is of utmost importance in nanotechnology, molecular electronics, and surface
      science. Here we propose two well-differentiated approaches, double printing
      based on microcontact printing (MU-cp) and molecular backfilling adsorption, to
      produce complex alkanethiol films. The resulting films on model Au surfaces were
      characterized by atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), and contact angle measurements. Double printing alkanethiols results in
      clear coexisting regions where no molecular displacement is observed,
      highlighting the slow diffusion rates of long alkanethiols and large attractive
      interaction between long alkyl chains. Exposing a single-print MU-cp Au substrate
      to an additional alkanethiol solution yields the formation of differently ordered
      domain boundaries with different thickness and micrometer lateral size. The high
      order is a result of enhanced molecular mobility and restructuring during
      solution backfilling. The formed molecular assemblies constitute an excellent
      testing ground for nanoscale phenomena that strongly depend on the nanoscale
      geometrical and chemical features of the surface such as designed functionality
      or corrosion initiation and inhibition.

PMID- 29221372
TI  - Surface-attached hydrogel coatings via C,H-insertion crosslinking for biomedical
      and bioanalytical applications (Review).
AB  - A novel method for the generation of surface-attached hydrogel coatings and their
      use in biomedical applications is discussed. This short review concentrates on
      surface architectures that are prepared from prepolymers carrying reactive groups
      suitable for crosslinking via C,H insertion reactions [C,H insertion crosslinking
      (CHic)]. Upon photochemical or thermal activation these groups do not only induce
      the crosslinking of the system, but also connect the forming gel to the surface
      as long as the surface itself consists of an organic material. C,H groups as the
      reaction partner are available in abundance at practically all types of organic
      surfaces such as biomaterials or polymers, rendering the technique almost
      universally applicable. Surface-attached gels prepared this way show unique
      swelling properties due to the confinement of the chains, as the obtained
      essentially two-dimensional gels can only swell in one dimension. This
      anisotropic swelling does not permit penetration of the layers by macromolecules
      so that the surfaces become bioinert, i.e., are strongly protein and cell
      repellent. It is discussed how this property can be used to control the
      interaction of surfaces with biological species ranging from the level of
      biomolecules to living cells. A combination of the CHic chemistry and
      microstructuring techniques opens further avenues for the study of the behavior
      of cells to the generation of novel bioanalytical devices.

PMID- 29221373
TI  - Note: Assessment of the SCAN+rVV10 functional for the structure of liquid water.
AB  - The performance of the SCAN+rVV10 functional in modeling the structural
      properties of liquid water is studied through constant-volume ab initio molecular
      dynamics simulations with both classical and quantum nuclei. The radial
      distribution functions are found to be slightly overstructured with respect to
      experiment, but overall similar to those achieved with the bare SCAN and the
      rVV10 functionals. From the pressures calculated during the dynamics, it is
      inferred that the SCAN+rVV10 functional leads to a noticeable overestimation of
      the density of liquid water.

PMID- 29221374
TI  - Coherent state mapping ring polymer molecular dynamics for non-adiabatic quantum
      propagations.
AB  - We introduce the coherent-state mapping ring polymer molecular dynamics (CS
      RPMD), a new method that accurately describes electronic non-adiabatic dynamics
      with explicit nuclear quantization. This new approach is derived by using
      coherent-state mapping representation for the electronic degrees of freedom (DOF)
      and the ring-polymer path-integral representation for the nuclear DOF. The CS
      RPMD Hamiltonian does not contain any inter-bead coupling term in the state
      dependent potential and correctly describes electronic Rabi oscillations. A
      classical equation of motion is used to sample initial configurations and
      propagate the trajectories from the CS-RPMD Hamiltonian. At the time equivalent
      to zero, the quantum Boltzmann distribution (QBD) is recovered by reweighting the
      sampled distribution with an additional phase factor. In a special limit that
      there is one bead for mapping variables and multiple beads for nuclei, CS-RPMD
      satisfies detailed balance and preserves an approximate QBD. Numerical tests of
      this method with a two-state model system show very good agreement with exact
      quantum results over a broad range of electronic couplings.

PMID- 29221375
TI  - Adaptive enhanced sampling with a path-variable for the simulation of protein
      folding and aggregation.
AB  - In this article, we present a novel adaptive enhanced sampling molecular dynamics
      (MD) method for the accelerated simulation of protein folding and aggregation. We
      introduce a path-variable L based on the un-biased momenta p and displacements dq
      for the definition of the bias s applied to the system and derive 3 algorithms:
      general adaptive bias MD, adaptive path-sampling, and a hybrid method which
      combines the first 2 methodologies. Through the analysis of the correlations
      between the bias and the un-biased gradient in the system, we find that the
      hybrid methodology leads to an improved force correlation and acceleration in the
      sampling of the phase space. We apply our method on SPC/E water, where we find a
      conservation of the average water structure. We then use our method to sample
      dialanine and the folding of TrpCage, where we find a good agreement with
      simulation data reported in the literature. Finally, we apply our methodologies
      on the initial stages of aggregation of a hexamer of Alzheimer's amyloid beta
      fragment 25-35 (Abeta 25-35) and find that transitions within the hexameric
      aggregate are dominated by entropic barriers, while we speculate that especially
      the conformation entropy plays a major role in the formation of the fibril as a
      rate limiting factor.

PMID- 29221376
TI  - Eigenstate-specific temperatures in two-level paramagnetic spin lattices.
AB  - Increasing interest in the thermodynamics of small and/or isolated systems, in
      combination with recent observations of negative temperatures of atoms in
      ultracold optical lattices, has stimulated the need for estimating the
      conventional, canonical temperature Tcconv of systems in equilibrium with heat
      baths using eigenstate-specific temperatures (ESTs). Four distinct ESTs
      continuous canonical, discrete canonical, continuous microcanonical, and discrete
      microcanonical-are accordingly derived for two-level paramagnetic spin lattices
      (PSLs) in external magnetic fields. At large N, the four ESTs are intensive,
      equal to Tcconv, and obey all four laws of thermodynamics. In contrast, for N <
      1000, the ESTs of most PSL eigenstates are non-intensive, differ from Tcconv, and
      violate each of the thermodynamic laws. Hence, in spite of their similarities to
      Tcconv at large N, the ESTs are not true thermodynamic temperatures. Even so,
      each of the ESTs manifests a unique functional dependence on energy which clearly
      specifies the magnitude and direction of their deviation from Tcconv; the ESTs
      are thus good temperature estimators for small PSLs. The thermodynamic
      uncertainty relation is obeyed only by the ESTs of small canonical PSLs; it is
      violated by large canonical PSLs and by microcanonical PSLs of any size. The ESTs
      of population-inverted eigenstates are negative (positive) when calculated using
      Boltzmann (Gibbs) entropies; the thermodynamic implications of these entropically
      induced differences in sign are discussed in light of adiabatic invariance of the
      entropies. Potential applications of the four ESTs to nanothermometers and to
      systems with long-range interactions are discussed.

PMID- 29221377
TI  - Communication: Mechanochemical fluctuation theorem and thermodynamics of self
      phoretic motors.
AB  - Microscopic dynamical aspects of the propulsion of nanomotors by self-phoretic
      mechanisms are considered. Propulsion by self-diffusiophoresis relies on the
      mechanochemical coupling between the fluid velocity field and the concentration
      fields induced by asymmetric catalytic reactions on the motor surface. The
      consistency between the thermodynamics of this coupling and the microscopic
      reversibility of the underlying molecular dynamics is investigated. For this
      purpose, a mechanochemical fluctuation theorem for the joint probability to find
      the motor at position r after n reactive events have occurred during the time
      interval t is derived, starting from coupled Langevin equations for the
      translational, rotational, and chemical fluctuations of self-phoretic motors. An
      important result that follows from this analysis is the identification of an
      effect that is reciprocal to self-propulsion by diffusiophoresis, which leads to
      a dependence of the reaction rate on the value of an externally applied force.

PMID- 29221378
TI  - Theoretical approaches for treating non-valence correlation-bound anions.
AB  - In this work, we use a model (H2O)4 cluster, the bent CO2 molecule, and
      tetracyanoethylene as systems to explore the applicability of various electronic
      structure methods for characterizing non-valence correlation-bound anion states.
      The methods examined include the algebraic diagrammatic construction, various
      equation-of-motion coupled cluster methods, orbital-optimized MP2, and Brueckner
      coupled cluster doubles with perturbative triples. We demonstrate that the key to
      treating this challenging class of anions is the use of methods that include
      adequate orbital relaxation in response to long-range dispersion-like correlation
      effects.

PMID- 29221379
TI  - Clearing out a maze: A model of chemotactic motion in porous media.
AB  - We study the anomalous dynamics of a biased "hungry" (or "greedy") random walk on
      a percolating cluster. The model mimics chemotaxis in a porous medium: In close
      resemblance to the 1980s arcade game PAC-MAN(r), the hungry random walker
      consumes food, which is initially distributed in the maze, and biases its
      movement towards food-filled sites. We observe that the mean-squared displacement
      of the process follows a power law with an exponent that is different from
      previously known exponents describing passive or active microswimmer dynamics.
      The change in dynamics is well described by a dynamical exponent that depends
      continuously on the propensity to move towards food. It results in slower
      differential growth when compared to the unbiased random walk.

PMID- 29221380
TI  - Halogen bonding properties of 4-iodopyrazole and 4-bromopyrazole explored by
      rotational spectroscopy and ab initio calculations.
AB  - The combination of halogen- and hydrogen-bonding capabilities possessed by 4
      bromopyrazole and 4-iodopyrazole has led to them being described as "magic
      bullets" for biochemical structure determination. Laser vaporisation was used to
      introduce each of these 4-halopyrazoles into an argon gas sample undergoing
      supersonic expansion prior to the recording of the rotational spectra of these
      molecules by chirped-pulse Fourier transform microwave spectroscopy. Data were
      obtained for four isotopologues of 4-bromopyrazole and two isotopologues of 4
      iodopyrazole. Isotopic substitutions were achieved at the hydrogens attached to
      the pyrrolic nitrogen atoms of both 4-halopyrazoles and at the bromine atom of 4
      bromopyrazole. The experimentally determined nuclear quadrupole coupling
      constants, chiaa(X) and chibb(X)-chicc(X), of the halogen atoms (where X is the
      halogen atom) of each molecule are compared with the results of the ab initio
      calculations and those for a range of other halogen-containing molecules. It is
      concluded that each of 4-bromopyrazole and 4-iodopyrazole will form halogen bonds
      that are broadly comparable in strength to those formed by CH3X and CF3X.

PMID- 29221381
TI  - Study of Li atom diffusion in amorphous Li3PO4 with neural network potential.
AB  - To clarify atomic diffusion in amorphous materials, which is important in novel
      information and energy devices, theoretical methods having both reliability and
      computational speed are eagerly anticipated. In the present study, we applied
      neural network (NN) potentials, a recently developed machine learning technique,
      to the study of atom diffusion in amorphous materials, using Li3PO4 as a
      benchmark material. The NN potential was used together with the nudged elastic
      band, kinetic Monte Carlo, and molecular dynamics methods to characterize Li
      vacancy diffusion behavior in the amorphous Li3PO4 model. By comparing these
      results with corresponding DFT calculations, we found that the average error of
      the NN potential is 0.048 eV in calculating energy barriers of diffusion paths,
      and 0.041 eV in diffusion activation energy. Moreover, the diffusion coefficients
      obtained from molecular dynamics are always consistent with those from ab initio
      molecular dynamics simulation, while the computation speed of the NN potential is
      3-4 orders of magnitude faster than DFT. Lastly, the structure of amorphous
      Li3PO4 and the ion transport properties in it were studied with the NN potential
      using a large supercell model containing more than 1000 atoms. The formation of
      P2O7 units was observed, which is consistent with the experimental
      characterization. The Li diffusion activation energy was estimated to be 0.55 eV,
      which agrees well with the experimental measurements.

PMID- 29221382
TI  - Detailed balance, internal consistency, and energy conservation in fragment
      orbital-based surface hopping.
AB  - We have recently introduced an efficient semi-empirical non-adiabatic molecular
      dynamics method for the simulation of charge transfer/transport in molecules and
      molecular materials, denoted fragment orbital-based surface hopping (FOB-SH) [J.
      Spencer et al., J. Chem. Phys. 145, 064102 (2016)]. In this method, the charge
      carrier wavefunction is expanded in a set of charge localized, diabatic
      electronic states and propagated in the time-dependent potential due to classical
      nuclear motion. Here we derive and implement an exact expression for the non
      adiabatic coupling vectors between the adiabatic electronic states in terms of
      nuclear gradients of the diabatic electronic states. With the non-adiabatic
      coupling vectors (NACVs) available, we investigate how different flavours of
      fewest switches surface hopping affect detailed balance, internal consistency,
      and total energy conservation for electron hole transfer in a molecular dimer
      with two electronic states. We find that FOB-SH satisfies detailed balance across
      a wide range of diabatic electronic coupling strengths provided that the
      velocities are adjusted along the direction of the NACV to satisfy total energy
      conservation upon a surface hop. This criterion produces the right fraction of
      energy-forbidden (frustrated) hops, which is essential for correct population of
      excited states, especially when diabatic couplings are on the order of the
      thermal energy or larger, as in organic semiconductors and DNA. Furthermore, we
      find that FOB-SH is internally consistent, that is, the electronic surface
      population matches the average quantum amplitudes, but only in the limit of small
      diabatic couplings. For large diabatic couplings, inconsistencies are observed as
      the decrease in excited state population due to frustrated hops is not matched by
      a corresponding decrease in quantum amplitudes. The derivation provided here for
      the NACV should be generally applicable to any electronic structure approach
      where the electronic Hamiltonian is constructed in a diabatic electronic state
      basis.

PMID- 29221383
TI  - Self-adaptive tensor network states with multi-site correlators.
AB  - We introduce the concept of self-adaptive tensor network states (SATNSs) based on
      multi-site correlators. The SATNS ansatz gradually extends its variational space
      incorporating the most important next-order correlators into the ansatz for the
      wave function. The selection of these correlators is guided by entanglement
      entropy measures from quantum information theory. By sequentially introducing
      variational parameters and adjusting them to the system under study, the SATNS
      ansatz achieves keeping their number significantly smaller than the total number
      of full-configuration interaction parameters. The SATNS ansatz is studied for
      manganocene in its lowest-energy sextet and doublet states; the latter of which
      is known to be difficult to describe. It is shown that the SATNS parametrization
      solves the convergence issues found for previous correlator-based tensor network
      states.

PMID- 29221384
TI  - The second virial coefficient of bounded Mie potentials.
AB  - The second virial coefficient (SVC) of bounded generalizations of the Mie m:n
      potential phi(r)=lambda[1/(aq+rq)m/q-1/(aq+rq)n/q], where lambda, a, q, m, and n
      are constants (a >= 0), is explored. The particle separation distance is r. This
      potential could be used as an effective interaction between polymeric dispersed
      colloidal particles of various degrees of interpenetrability. The SVC is negative
      for all temperatures for a, greater than a critical value, ac, which coincides
      with the range of a, where the system is thermodynamically unstable. The Boyle
      temperature and the temperature at which the SVC is a maximum diverge to
      +infinity as a -> ac from below. Various series expansion expressions for the SVC
      are derived following on from those derived for the Mie potential itself (i.e., a
      = 0) in the study of Heyes et al. [J. Chem. Phys. 145, 084505 (2016)]. Formulas
      based on an expansion of the exponential in the Mayer function definition of the
      SVC are formally convergent, but pose numerical problems for the useful range of
      a < 1. High temperature expansion (HTE) formulas extending those in the previous
      publication are derived, which in contrast converge rapidly for the full a range.
      The HTE formulas derived in this work could be useful in guiding the choice of
      nucleation and growth experimental conditions for dispersed soft polymeric
      particles. Inter alia, the SVC of the inverse power special case of the Bounded
      Mie potential, i.e., phi(r)=1/(aq+rq)m/q, are also derived.

PMID- 29221385
TI  - Transient anion spectra of the potential radiosensitizers 5-cyanateuracil and 5
      thiocyanateuracil.
AB  - We report on the low energy anion spectra of 5-cyanateuracil (5-OCNU) and 5
      thiocyanateouracil (5-SCNU), which have been the suggested potential
      radiosensitizers for use in cancer therapy [L. Chomicz et al., J. Phys. Chem.
      Lett. 4, 2853-2857 (2013)]. Employing bound state and scattering calculations, we
      obtained, for both molecules, a dipole bound state, a pi* valence bound state,
      and four pi* resonances, besides a sigmaSCN* resonance for 5-SCNU. The cyanate
      and thiocyanate substituents give rise to additional long-lived pi* resonances,
      compared to 5-halouracil radiosensitizers. From the reaction thresholds and the
      expected vibronic couplings among the anion states, efficient production of SCN
      and CN anions and radical fragments should be observed in dissociative electron
      attachment measurements for 5-SCNU. The corresponding dissociation processes in 5
      OCNU are expected to be less effective in view of the lack of a long-lived
      sigmaOCN* shape resonance and the little sigma* admixture into the pi* resonances
      located on the cyanate group. The present results thus indicate 5-SCNU as a more
      promising radiosensitizer at sub-excitation energies.

PMID- 29221386
TI  - Finite temperature dynamics of a Holstein polaron: The thermo-field dynamics
      approach.
AB  - Combining the multiple Davydov D2 Ansatz with the method of thermo-field
      dynamics, we study finite temperature dynamics of a Holstein polaron on a
      lattice. It has been demonstrated, using the hierarchy equations of motion method
      as a benchmark, that our approach provides an efficient, robust description of
      finite temperature dynamics of the Holstein polaron in the simultaneous presence
      of diagonal and off-diagonal exciton-phonon coupling. The method of thermo-field
      dynamics handles temperature effects in the Hilbert space with key numerical
      advantages over other treatments of finite-temperature dynamics based on quantum
      master equations in the Liouville space or wave function propagation with Monte
      Carlo importance sampling. While for weak to moderate diagonal coupling
      temperature increases inhibit polaron mobility, it is found that off-diagonal
      coupling induces phonon-assisted transport that dominates at high temperatures.
      Results on the mean square displacements show that band-like transport features
      dominate the diagonal coupling cases, and there exists a crossover from band-like
      to hopping transport with increasing temperature when including off-diagonal
      coupling. As a proof of concept, our theory provides a unified treatment of
      coherent and incoherent transport in molecular crystals and is applicable to any
      temperature.

PMID- 29221387
TI  - Two-body perturbation theory versus first order perturbation theory: A comparison
      based on the square-well fluid.
AB  - We show that the Zwanzig first-order perturbation theory can be obtained directly
      from a truncated Taylor series expansion of a two-body perturbation theory and
      that such truncation provides a more accurate prediction of thermodynamic
      properties than the full two-body perturbation theory. This unexpected result is
      explained by the quality of the resulting approximation for the fluid radial
      distribution function. We prove that the first-order and the two-body
      perturbation theories are based on different approximations for the fluid radial
      distribution function. To illustrate the calculations, the square-well fluid is
      adopted. We develop an analytical expression for the two-body perturbed Helmholtz
      free energy for the square-well fluid. The equation of state obtained using such
      an expression is compared to the equation of state obtained from the first-order
      approximation. The vapor-liquid coexistence curve and the supercritical
      compressibility factor of a square-well fluid are calculated using both equations
      of state and compared to Monte Carlo simulation data. Finally, we show that the
      approximation for the fluid radial distribution function given by the first-order
      perturbation theory provides closer values to the ones calculated via Monte Carlo
      simulations. This explains why such theory gives a better description of the
      fluid thermodynamic behavior.

PMID- 29221388
TI  - Guided ion beam and theoretical studies of the bond energy of SmS.
AB  - Previous work has shown that atomic samarium cations react with carbonyl sulfide
      to form SmS+ + CO in an exothermic and barrierless process. To characterize this
      reaction further, the bond energy of SmS+ is determined in the present study
      using guided ion beam tandem mass spectrometry. Reactions of SmS+ with Xe, CO,
      and O2 are examined. Results for collision-induced dissociation processes with
      all three molecules along with the endothermicity of the SmS+ + CO -> Sm+ + COS
      exchange reaction are combined to yield D0(Sm+-S) = 3.37 +/- 0.20 eV. The CO and
      O2 reactions also yield a SmSO+ product, with measured endothermicities that
      indicate D0(SSm+-O) = 3.73 +/- 0.16 eV and D0(OSm+-S) = 1.38 +/- 0.27 eV. The
      SmS+ bond energy is compared with theoretical values characterized at several
      levels of theory, including CCSD(T) complete basis set extrapolations using all
      electron basis sets. Multireference configuration interaction calculations with
      explicit spin-orbit calculations along with composite thermochemistry using the
      Feller-Peterson-Dixon method and all-electron basis sets were also explored for
      SmS+, and for comparison, SmO, SmO+, and EuO.

PMID- 29221389
TI  - Nuclear spin/parity dependent spectroscopy and predissociation dynamics in vOH =
      2 <- 0 overtone excited Ne-H2O clusters: Theory and experiment.
AB  - Vibrationally state selective overtone spectroscopy and state- and nuclear spin
      dependent predissociation dynamics of weakly bound ortho- and para-Ne-H2O
      complexes (D0(ortho) = 34.66 cm-1 and D0(para) = 31.67 cm-1) are reported, based
      on near-infrared excitation of van der Waals cluster bands correlating with vOH =
      2 <- 0 overtone transitions (|02-> and |02+>) out of the ortho (101) and para
      (000) internal rotor states of the H2O moiety. Quantum theoretical calculations
      for nuclear motion on a high level potential energy surface [CCSD(T)/VnZf12 (n =
      3, 4)], corrected for basis set superposition error and extrapolated to the
      complete basis set (CBS) limit, are employed to successfully predict and assign
      Pi-Sigma, Sigma-Sigma, and Sigma-Pi infrared bands in the spectra, where Sigma or
      Pi represent approximate projections of the body-fixed H2O angular momentum along
      the Ne-H2O internuclear axis. IR-UV pump-probe experimental capabilities permit
      real-time measurements of the vibrational predissociation dynamics, which
      indicate facile intramolecular vibrational energy transfer from the H2O vOH = 2
      overtone vibrations into the VdWs (van der Waals) dissociation coordinate on the
      tauprediss = 15-25 ns time scale. Whereas all predicted strong transitions in the
      ortho-Ne-H2O complexes are readily detected and assigned, vibrationally mediated
      photolysis spectra for the corresponding para-Ne-H2O bands are surprisingly
      absent despite ab initio predictions of Q-branch intensities with S/N > 20-40.
      Such behavior signals the presence of highly selective nuclear spin ortho-para
      predissociation dynamics in the upper state, for which we offer a simple
      mechanism based on Ne-atom mediated intramolecular vibrational relaxation in the
      H2O subunit (i.e., |02+/-> -> {|01+/->; v2 = 2}), which is confirmed by the ab
      initio energy level predictions and the nascent OH rotational (N), spin orbit
      (Pi1/2,3/2), and lambda doublet product distributions.

PMID- 29221390
TI  - sigma-SCF: A direct energy-targeting method to mean-field excited states.
AB  - The mean-field solutions of electronic excited states are much less accessible
      than ground state (e.g., Hartree-Fock) solutions. Energy-based optimization
      methods for excited states, like Delta-SCF (self-consistent field), tend to fall
      into the lowest solution consistent with a given symmetry-a problem known as
      "variational collapse." In this work, we combine the ideas of direct energy
      targeting and variance-based optimization in order to describe excited states at
      the mean-field level. The resulting method, sigma-SCF, has several advantages.
      First, it allows one to target any desired excited state by specifying a single
      parameter: a guess of the energy of that state. It can therefore, in principle,
      find all excited states. Second, it avoids variational collapse by using a
      variance-based, unconstrained local minimization. As a consequence, all states
      ground or excited-are treated on an equal footing. Third, it provides an
      alternate approach to locate Delta-SCF solutions that are otherwise hardly
      accessible by the usual non-aufbau configuration initial guess. We present
      results for this new method for small atoms (He, Be) and molecules (H2, HF). We
      find that sigma-SCF is very effective at locating excited states, including
      individual, high energy excitations within a dense manifold of excited states.
      Like all single determinant methods, sigma-SCF shows prominent spin-symmetry
      breaking for open shell states and our results suggest that this method could be
      further improved with spin projection.

PMID- 29221391
TI  - Quantum interference in multi-branched molecules: The exact transfer matrix
      solutions.
AB  - We present a transfer matrix formalism for studying quantum interference in a
      single molecule electronic system with internal branched structures. Based on the
      Schrodinger equation with the Bethe ansatz and employing Kirchhoff's rule for
      quantum wires, we derive a general closed-form expression for the transmission
      and reflection amplitudes of a two-port quantum network. We show that the
      transport through a molecule with complex internal structures can be reduced to
      that of a single two-port scattering unit, which contains all the information of
      the original composite molecule. Our method allows for the calculation of the
      transmission coefficient for various types of individual molecular modules giving
      rise to different resonant transport behaviors such as the Breit-Wigner, Fano,
      and Mach-Zehnder resonances. As an illustration, we first re-derive the
      transmittance of the Aharonov-Bohm ring, and then we apply our formulation to N
      identical parity-time (PT)-symmetric potentials, connected in series as well as
      in parallel. It is shown that the spectral singularities and PT-symmetric
      transitions of single scattering cells may be observed in coupled systems. Such
      transitions may occur at the same or distinct values of the critical parameters,
      depending on the connection modes under which the scattering objects are coupled.

PMID- 29221392
TI  - Spectroscopic and theoretical studies on the structural, electronic, and optical
      properties of zinc octaethylporphyrin/C60 co-deposited films.
AB  - We have examined the structural, electronic, and optical properties of zinc
      octaethylporphyrin [Zn(OEP)]/C60 co-deposited films to elucidate the donor (D)
      acceptor (A) interactions at the D/A interface of heterojunction organic solar
      cells (OSCs), using Fourier-transform infrared (FT-IR) spectroscopy, X-ray
      diffraction (XRD), ultraviolet-visible (UV-vis) spectroscopy, and
      photoluminescence (PL) spectroscopy in combination with first-principles and semi
      empirical calculations. The FT-IR and XRD results indicated that Zn(OEP) and C60
      were mixed with each other at the molecular level in the co-deposited film. The
      theoretical calculations suggested that in the interfacial region, it is
      energetically preferable for the C60 molecule to face the center of the planar
      structure of Zn(OEP) at a distance of 2.8 A rather than the edge of the structure
      at a distance of 5.0 A. After consideration of the C60 solvent effects, this
      coordination model for C60-Zn(OEP) adequately explained the line shift of the UV
      vis peaks with respect to the proportion of C60 in the co-deposited films. A
      comparison of the energy level diagrams of Zn(OEP) before and after the
      interaction with C60 revealed that the LUMO, HOMO, and HOMO-1 were significantly
      affected by the interaction with C60. In particular, the HOMO-1 wave function
      became spread over a portion of C60, although the charge transfer between Zn(OEP)
      and C60 was almost negligible. Since no PL peaks (S1 -> S0) from the excited
      Soret band of Zn(OEP) were observed for the Zn(OEP)/C60 co-deposited films, the
      D/A mixing layers played a crucial role in completely dissolving the
      photogenerated excitons to electrons-hole pairs that cause the short-circuit
      current, which is relevant to improving the energy conversion efficiency of OSCs.

PMID- 29221393
TI  - Equation of state and Helmholtz free energy for the atomic system of the
      repulsive Lennard-Jones particles.
AB  - Simple and accurate expressions are presented for the equation of state (EOS) and
      absolute Helmholtz free energy of a system composed of simple atomic particles
      interacting through the repulsive Lennard-Jones potential model in the fluid and
      solid phases. The introduced EOS has 17 and 22 coefficients for fluid and solid
      phases, respectively, which are regressed to the Monte Carlo (MC) simulation data
      over the reduced temperature range of 0.6<=T*<=6.0 and the packing fraction range
      of 0.1 <= eta <= 0.72. The average absolute relative percent deviation in fitting
      the EOS parameters to the MC data is 0.06 and 0.14 for the fluid and solid
      phases, respectively. The thermodynamic integration method is used to calculate
      the free energy using the MC simulation results. The Helmholtz free energy of the
      ideal gas is employed as the reference state for the fluid phase. For the solid
      phase, the values of the free energy at the reduced density equivalent to the
      close-packed of a hard sphere are used as the reference state. To check the
      validity of the predicted values of the Helmholtz free energy, the Widom particle
      insertion method and the Einstein crystal technique of Frenkel and Ladd are
      employed. The results obtained from the MC simulation approaches are well agreed
      to the EOS results, which show that the proposed model can reliably be utilized
      in the framework of thermodynamic theories.

PMID- 29221394
TI  - Mesoscale simulations of confined Nafion thin films.
AB  - The morphology and transport properties of thin films of the ionomer Nafion, with
      thicknesses on the order of the bulk cluster size, have been investigated as a
      model system to explain the anomalous behaviour of catalyst/electrode-polymer
      interfaces in membrane electrode assemblies. We have employed dissipative
      particle dynamics (DPD) to investigate the interaction of water and fluorocarbon
      chains, with carbon and quartz as confining materials, for a wide range of
      operational water contents and film thicknesses. We found confinement-induced
      clustering of water perpendicular to the thin film. Hydrophobic carbon forms a
      water depletion zone near the film interface, whereas hydrophilic quartz results
      in a zone with excess water. There are, on average, oscillating water-rich and
      fluorocarbon-rich regions, in agreement with experimental results from neutron
      reflectometry. Water diffusivity shows increasing directional anisotropy of up to
      30% with decreasing film thickness, depending on the hydrophilicity of the
      confining material. A percolation analysis revealed significant differences in
      water clustering and connectivity with the confining material. These findings
      indicate the fundamentally different nature of ionomer thin films, compared to
      membranes, and suggest explanations for increased ionic resistances observed in
      the catalyst layer.

PMID- 29221395
TI  - Reassigning the CaH+ 11Sigma -> 21Sigma vibronic transition with CaD.
AB  - We observe vibronic transitions in CaD+ between the 11Sigma and 21Sigma
      electronic states by resonance enhanced multiphoton photodissociation
      spectroscopy in a Coulomb crystal. The vibronic transitions are compared with
      previous measurements on CaH+. The result is a revised assignment of the CaH+
      vibronic levels and a disagreement with multi-state-complete-active-space second
      order perturbation theory theoretical calculations by approximately 700 cm-1.
      Updated high-level coupled-cluster calculations that include core-valence
      correlations reduce the disagreement between theory and experiment to 300 cm-1.

PMID- 29221396
TI  - Perspective: Highly stable vapor-deposited glasses.
AB  - This article describes recent progress in understanding highly stable glasses
      prepared by physical vapor deposition and provides perspective on further
      research directions for the field. For a given molecule, vapor-deposited glasses
      can have higher density and lower enthalpy than any glass that can be prepared by
      the more traditional route of cooling a liquid, and such glasses also exhibit
      greatly enhanced kinetic stability. Because vapor-deposited glasses can approach
      the bottom of the amorphous part of the potential energy landscape, they provide
      insights into the properties expected for the "ideal glass." Connections between
      vapor-deposited glasses, liquid-cooled glasses, and deeply supercooled liquids
      are explored. The generality of stable glass formation for organic molecules is
      discussed along with the prospects for stable glasses of other types of
      materials.

PMID- 29221397
TI  - Effects of nanoparticle heating on the structure of a concentrated aqueous salt
      solution.
AB  - The effects of a rapidly heated nanoparticle on the structure of a concentrated
      aqueous salt solution are studied using molecular dynamics simulations. A diamond
      like nanoparticle of radius 20 A is immersed in a sodium-chloride solution at 20%
      above the experimental saturation concentration and equilibrated at T = 293 K and
      P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees
      Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is
      observed that after 2-3 ns, the salt ions are depleted far more than water
      molecules from a proximal zone 15-25 A from the nanoparticle surface. This leads
      to a transient reduction in molality in the proximal zone and an increase in ion
      clustering in the distal zone. At longer times, ions begin to diffuse back into
      the proximal zone. It is speculated that the formation of proximal and distal
      zones, and the increase in ion clustering, plays a role in the mechanism of
      nonphotochemical laser-induced nucleation.

PMID- 29221398
TI  - A multiscale transport model for non-classical nanochannel electroosmosis.
AB  - We present a multiscale model describing the electroosmotic flow (EOF) in
      nanoscale channels involving high surface charge liquid-solid interfaces. The
      departure of the EOF velocity profiles from classical predictions is explained by
      the non-classical charge distribution in the confined direction including charge
      inversion, reduced mobility of interfacial counter-ions, and subsequent
      enhancement of the local viscosity. The excess component of the local solvent
      viscosity is modeled by the local application of the Fuoss-Onsager theory and the
      Hubbard-Onsager electro-hydrodynamic equation based dielectric friction theory.
      The electroosmotic slip velocity is estimated from the interfacial friction
      coefficient, which in turn is calculated using a generalized Langevin equation
      based dynamical framework. The proposed model for local viscosity enhancement and
      EOF velocity shows good agreement of corresponding physical quantities against
      relevant molecular dynamics simulation results, including the cases of anomalous
      transport such as EOF reversal.

PMID- 29221399
TI  - Long-range coupling between ATP-binding and lever-arm regions in myosin via
      dielectric allostery.
AB  - A protein molecule is a dielectric substance, so the binding of a ligand is
      expected to induce dielectric response in the protein molecule, considering that
      ligands are charged or polar in general. We previously reported that binding of
      adenosine triphosphate (ATP) to molecular motor myosin actually induces such a
      dielectric response in myosin due to the net negative charge of ATP. By this
      dielectric response, referred to as "dielectric allostery," spatially separated
      two regions in myosin, the ATP-binding region and the actin-binding region, are
      allosterically coupled. In this study, from the statistically stringent analyses
      of the extensive molecular dynamics simulation data obtained in the ATP-free and
      the ATP-bound states, we show that there exists the dielectric allostery that
      transmits the signal of ATP binding toward the distant lever-arm region. The ATP
      binding-induced electrostatic potential change observed on the surface of the
      main domain induced a movement of the converter subdomain from which the lever
      arm extends. The dielectric response was found to be caused by an underlying
      large-scale concerted rearrangement of the electrostatic bond network, in which
      highly conserved charged/polar residues are involved. Our study suggests the
      importance of the dielectric property for molecular machines in exerting their
      function.

PMID- 29221400
TI  - A long-range ordered array of copper tetrameric units embedded in an on-surface
      metal organic framework.
AB  - We report on the assembly of a highly ordered array of copper tetrameric
      clusters, coordinated into a metal-organic network. The ordered cluster array has
      been achieved by the deposition of tetrahydroxyquinone molecules on the Cu(111)
      surface at room temperature, and subsequent thermally activated dehydrogenation
      with the formation of tetraoxyquinone tetra-anions with a 4 * 4 periodicity. The
      supramolecular organic network acts as a spacer for the highly ordered two
      dimensional network of copper tetramers at the very surface.

PMID- 29221401
TI  - Analytical energy gradients for explicitly correlated wave functions. I.
      Explicitly correlated second-order Moller-Plesset perturbation theory.
AB  - We present the theory and algorithms for computing analytical energy gradients
      for explicitly correlated second-order Moller-Plesset perturbation theory (MP2
      F12). The main difficulty in F12 gradient theory arises from the large number of
      two-electron integrals for which effective two-body density matrices and integral
      derivatives need to be calculated. For efficiency, the density fitting
      approximation is used for evaluating all two-electron integrals and their
      derivatives. The accuracies of various previously proposed MP2-F12 approximations
      [3C, 3C(HY1), 3*C(HY1), and 3*A] are demonstrated by computing equilibrium
      geometries for a set of molecules containing first- and second-row elements,
      using double-zeta to quintuple-zeta basis sets. Generally, the convergence of the
      bond lengths and angles with respect to the basis set size is strongly improved
      by the F12 treatment, and augmented triple-zeta basis sets are sufficient to
      closely approach the basis set limit. The results obtained with the different
      approximations differ only very slightly. This paper is the first step towards
      analytical gradients for coupled-cluster singles and doubles with perturbative
      treatment of triple excitations, which will be presented in the second part of
      this series.

PMID- 29221402
TI  - Transition path time distributions.
AB  - Biomolecular folding, at least in simple systems, can be described as a two state
      transition in a free energy landscape with two deep wells separated by a high
      barrier. Transition paths are the short part of the trajectories that cross the
      barrier. Average transition path times and, recently, their full probability
      distribution have been measured for several biomolecular systems, e.g., in the
      folding of nucleic acids or proteins. Motivated by these experiments, we have
      calculated the full transition path time distribution for a single stochastic
      particle crossing a parabolic barrier, including inertial terms which were
      neglected in previous studies. These terms influence the short time scale
      dynamics of a stochastic system and can be of experimental relevance in view of
      the short duration of transition paths. We derive the full transition path time
      distribution as well as the average transition path times and discuss the
      similarities and differences with the high friction limit.

PMID- 29221403
TI  - A molecular Debye-Huckel theory of solvation in polar fluids: An extension of the
      Born model.
AB  - A dielectric response theory of solvation beyond the conventional Born model for
      polar fluids is presented. The dielectric response of a polar fluid is described
      by a Born response mode and a linear combination of Debye-Huckel-like response
      modes that capture the nonlocal response of polar fluids. The Born mode is
      characterized by a bulk dielectric constant, while a Debye-Huckel mode is
      characterized by its corresponding Debye screening length. Both the bulk
      dielectric constant and the Debye screening lengths are determined from the bulk
      dielectric function of the polar fluid. The linear combination coefficients of
      the response modes are evaluated in a self-consistent way and can be used to
      evaluate the electrostatic contribution to the thermodynamic properties of a
      polar fluid. Our theory is applied to a dipolar hard sphere fluid as well as
      interaction site models of polar fluids such as water, where the electrostatic
      contribution to their thermodynamic properties can be obtained accurately.

PMID- 29221404
TI  - Ab initio simulations of bond breaking in sulfur crosslinked isoprene oligomer
      units.
AB  - Sulfur crosslinked polyisoprene (rubber) is used in important material components
      for a number of technical tasks (e.g., in tires and sealings). If mechanical
      stress, like tension or shear, is applied on these material components, the
      sulfur crosslinks suffer from homolytic bond breaking. In this work, we have
      simulated the bond breaking mechanism of sulfur crosslinks between polyisoprene
      chains using Car-Parrinello molecular dynamic simulations and investigated the
      maximum forces which can be resisted by the crosslinks. Small model systems with
      crosslinks formed by chains of N = 1 to N = 6 sulfur atoms have been simulated
      with the slow growth-technique, known from the literature. The maximum force can
      be thereby determined from the calculated energies as a function of strain
      (elongation). The stability of the crosslink under strain is quantified in terms
      of the maximum force that can be resisted by the system before the crosslink
      breaks. As shown by our simulations, this maximum force decreases with the sulfur
      crosslink length N in a step like manner. Our findings indicate that in bridges
      with N = 1, 2, and 3 sulfur atoms predominantly, carbon-sulfur bonds break, while
      in crosslinks with N > 3, the breaking of a sulfur-sulfur bond is the dominant
      failure mechanism. The results are explained within a simple chemical bond model,
      which describes how the delocalization of the electrons in the generated radicals
      can lower their electronic energy and decrease the activation barriers. It is
      described which of the double bonds in the isoprene units are involved in the
      mechanochemistry of crosslinked rubber.

PMID- 29221405
TI  - On the non-stationary generalized Langevin equation.
AB  - In molecular dynamics simulations and single molecule experiments, observables
      are usually measured along dynamic trajectories and then averaged over an
      ensemble ("bundle") of trajectories. Under stationary conditions, the time
      evolution of such averages is described by the generalized Langevin equation. By
      contrast, if the dynamics is not stationary, it is not a priori clear which form
      the equation of motion for an averaged observable has. We employ the formalism of
      time-dependent projection operator techniques to derive the equation of motion
      for a non-equilibrium trajectory-averaged observable as well as for its non
      stationary auto-correlation function. The equation is similar in structure to the
      generalized Langevin equation but exhibits a time-dependent memory kernel as well
      as a fluctuating force that implicitly depends on the initial conditions of the
      process. We also derive a relation between this memory kernel and the
      autocorrelation function of the fluctuating force that has a structure similar to
      a fluctuation-dissipation relation. In addition, we show how the choice of the
      projection operator allows us to relate the Taylor expansion of the memory kernel
      to data that are accessible in MD simulations and experiments, thus allowing us
      to construct the equation of motion. As a numerical example, the procedure is
      applied to Brownian motion initialized in non-equilibrium conditions and is shown
      to be consistent with direct measurements from simulations.

PMID- 29221406
TI  - Atomistic simulations of the equation of state and hybridization of liquid carbon
      at a temperature of 6000 K in the pressure range of 1-25 GPa.
AB  - The equation of state and the structure of liquid carbon are studied by molecular
      simulation. Both classical and quantum molecular dynamics (QMD) are used to
      calculate the equation of state and the distribution of chemical bonds at 6000 K
      in the pressure range 1-25 GPa. Our calculations and results of other authors
      show that liquid carbon has a fairly low density on the order of 1.2-1.35 g/cm3
      at pressures about 1 GPa. Owing to the coordination number analysis, this fact
      can be attributed to the high content of sp1-bonded atoms (more than 50%
      according to our ab initio computations). Six empirical potentials have been
      tested in order to describe the density dependence of pressure and structure at
      6000 K. As a result, only one potential, ReaxFF/lg, was able to reproduce the QMD
      simulations for both the equation of state and the fraction of sp1, sp2, sp3
      bonded atoms.

PMID- 29221407
TI  - Communication: Self-assembly of a model supramolecular polymer studied by replica
      exchange with solute tempering.
AB  - Conventional molecular-dynamics (cMD) simulation has a well-known limitation in
      accessible time and length scales, and thus various enhanced sampling techniques
      have been proposed to alleviate the problem. In this paper, we explore the
      utility of replica exchange with solute tempering (REST) (i.e., a variant of
      Hamiltonian replica exchange methods) to simulate the self-assembly of a
      supramolecular polymer in explicit solvent and compare the performance with
      temperature-based replica exchange MD (T-REMD) as well as cMD. As a test system,
      we consider a relatively simple all-atom model of supramolecular polymerization
      (namely, benzene-1,3,5-tricarboxamides in methylcyclohexane solvent). Our results
      show that both REST and T-REMD are able to predict highly ordered polymer
      structures with helical H-bonding patterns, in contrast to cMD which completely
      fails to obtain such a structure for the present model. At the same time, we have
      also experienced some technical challenge (i.e., aggregation-dispersion
      transition and the resulting bottleneck for replica traversal), which is
      illustrated numerically. Since the computational cost of REST scales more
      moderately than T-REMD, we expect that REST will be useful for studying the self
      assembly of larger systems in solution with enhanced rearrangement of monomers.

PMID- 29221409
TI  - The gas phase structure of alpha-pinene, a main biogenic volatile organic
      compound.
AB  - The gas phase structure of the bicyclic atmospheric aerosol precursor alpha
      pinene was investigated employing a combination of quantum chemical calculation
      and Fourier transform microwave spectroscopy coupled to a supersonic jet
      expansion. The very weak rotational spectra of the parent species and all singly
      substituted 13C in natural abundance have been identified, from 2 to 20 GHz, and
      fitted to Watson's Hamiltonian model. The rotational constants were used together
      with geometrical parameters from density functional theory and ab initio
      calculations to determine the rs, r0, and rm(1) structures of the skeleton,
      without any structural assumption in the fit concerning the heavy atoms. The
      double C=C bond was found to belong to a quasiplanar skeleton structure
      containing 6 carbon atoms. Comparison with solid phase structure is reported. The
      significant differences of alpha-pinene in gas phase and other gas phase bicyclic
      monoterpene structures (beta-pinene, nopinone, myrtenal, and
      bicyclo[3.1.1]heptane) are discussed.

PMID- 29221408
TI  - Exploring a multi-scale method for molecular simulation in continuum solvent
      model: Explicit simulation of continuum solvent as an incompressible fluid.
AB  - We explored a multi-scale algorithm for the Poisson-Boltzmann continuum solvent
      model for more robust simulations of biomolecules. In this method, the continuum
      solvent/solute interface is explicitly simulated with a numerical fluid dynamics
      procedure, which is tightly coupled to the solute molecular dynamics simulation.
      There are multiple benefits to adopt such a strategy as presented below. At this
      stage of the development, only nonelectrostatic interactions, i.e., van der Waals
      and hydrophobic interactions, are included in the algorithm to assess the quality
      of the solvent-solute interface generated by the new method. Nevertheless,
      numerical challenges exist in accurately interpolating the highly nonlinear van
      der Waals term when solving the finite-difference fluid dynamics equations. We
      were able to bypass the challenge rigorously by merging the van der Waals
      potential and pressure together when solving the fluid dynamics equations and by
      considering its contribution in the free-boundary condition analytically. The
      multi-scale simulation method was first validated by reproducing the solute
      solvent interface of a single atom with analytical solution. Next, we performed
      the relaxation simulation of a restrained symmetrical monomer and observed a
      symmetrical solvent interface at equilibrium with detailed surface features
      resembling those found on the solvent excluded surface. Four typical small
      molecular complexes were then tested, both volume and force balancing analyses
      showing that these simple complexes can reach equilibrium within the simulation
      time window. Finally, we studied the quality of the multi-scale solute-solvent
      interfaces for the four tested dimer complexes and found that they agree well
      with the boundaries as sampled in the explicit water simulations.

PMID- 29221410
TI  - Trapping and escape in a turbid medium.
AB  - We investigate the absorption of diffusing molecules in a fluid-filled spherical
      beaker that contains many small reactive traps. The molecules are absorbed either
      by hitting a trap or by escaping via the beaker walls. In the physical situation
      where the number N of traps is large and their radii a are small compared to the
      beaker radius R, the fraction of molecules E that escape to the beaker wall and
      the complementary fraction T that eventually are absorbed by the traps depend
      only on the dimensionless parameter combination lambda = Na/R. We compute E and T
      as a function of lambda for a spherical beaker and for beakers of other three
      dimensional shapes. The asymptotic behavior is found to be universal: 1 - E ~
      lambda for lambda -> 0 and E ~ lambda-1/2 for lambda -> infinity.

PMID- 29221411
TI  - Augmented potential, energy densities, and virial relations in the weak- and
      strong-interaction limits of DFT.
AB  - The augmented potential introduced by Levy and Zahariev [Phys. Rev. Lett. 113,
      113002 (2014)] is shifted with respect to the standard exchange-correlation
      potential of the Kohn-Sham density functional theory by a density-dependent
      constant that makes the total energy become equal to the sum of the occupied
      orbital energies. In this work, we analyze several features of this approach,
      focusing on the limit of infinite coupling strength and studying the shift and
      the corresponding energy density at different correlation regimes. We present and
      discuss coordinate scaling properties of the augmented potential, study its
      connection to the response potential, and use the shift to analyze the classical
      jellium and uniform gas models. We also study other definitions of the energy
      densities in relation to the functional construction by local interpolations
      along the adiabatic connection. Our findings indicate that the energy density
      that is defined in terms of the electrostatic potential of the exchange
      correlation hole is particularly well suited for this purpose.

PMID- 29221412
TI  - Scaling behavior of knotted random polygons and self-avoiding polygons:
      Topological swelling with enhanced exponent.
AB  - We show that the average size of self-avoiding polygons (SAPs) with a fixed knot
      is much larger than that of no topological constraint if the excluded volume is
      small and the number of segments is large. We call it topological swelling. We
      argue an "enhancement" of the scaling exponent for random polygons with a fixed
      knot. We study them systematically through SAP consisting of hard cylindrical
      segments with various different values of the radius of segments. Here we mean by
      the average size the mean-square radius of gyration. Furthermore, we show
      numerically that the topological balance length of a composite knot is given by
      the sum of those of all constituent prime knots. Here we define the topological
      balance length of a knot by such a number of segments that topological entropic
      repulsions are balanced with the knot complexity in the average size. The
      additivity suggests the local knot picture.

PMID- 29221413
TI  - Heterogeneous nucleation on rough surfaces: Generalized Gibbs' approach.
AB  - Heterogeneous nucleation (condensation) of liquid droplets from vapor (gas) on a
      defective solid surface is considered. The vapor is described by the van der
      Waals equation of state. The dependence of nucleating droplet parameters on
      droplet size is accounted for within the generalized Gibbs approach. As a surface
      defect, a conic void is taken. This choice allows us to simplify the analysis and
      at the same time to follow the main aspects of the influence of the surface
      roughness on the nucleation process. Similar to condensation on ideal planar
      surfaces, the contact angle and catalytic factor for heterogeneous nucleation on
      a rough surface depend on the degree of vapor overcooling. In the case of droplet
      formation on a hydrophilic surface of a conic void, the nucleation rate
      considerably increases in comparison with the condensation on a planar interface.
      In fact, the presence of a defect on the hydrophilic surface leads to a
      considerable shift of the spinodal towards lower supersaturation in comparison
      with heterogeneous nucleation on a planar interface. With the decrease in the
      void cone angle, the heterogeneous spinodal approaches the binodal, and the
      region of metastability is diminished at the expense of the instability region.

PMID- 29221414
TI  - Orientation dependence of the work function for metal nanocrystals.
AB  - Work function values measured at different surfaces of a metal are usually
      different. This raises an interesting question: What is the work function of a
      nano-size crystal, where differently oriented facets can be adjacent? Work
      functions of metallic nanocrystals are also of significant practical interest,
      especially in catalytic applications. Using real space pseudopotentials
      constructed within density functional theory, we compute the local work function
      of large aluminum and gold nanocrystals. We investigate how the local work
      function follows the change of the surface plane orientation around multifaceted
      nanocrystals, and we establish the importance of the orbital character near the
      Fermi level in determining work function differences between facets.

PMID- 29221415
TI  - Water-water correlations in electrolyte solutions probed by hyper-Rayleigh
      scattering.
AB  - Long-range ion-induced correlations between water molecules have been observed by
      second-harmonic or hyper-Rayleigh scattering experiments with conflicting
      results. The most recent work observed a large difference between the results for
      H2O and D2O, and large discrepancies with the previously proposed theory.
      However, the present observations are in quantitative agreement with the model
      where the ion electric field induces second harmonic generation by the water
      molecules, and ion-ion correlations given by the Debye-Huckel theory account for
      intensity saturation at high ion concentration. This work compares experimental
      results with theory and addresses the apparent discrepancies with previous
      experiments.

PMID- 29221416
TI  - Identification of a new low energy 1u state in dicopper with resonant four-wave
      mixing.
AB  - The low energy electronic structure of the copper dimer has been re-investigated
      using non-linear four-wave mixing spectroscopy and high level ab initio
      calculations. In addition to the measurement of the previously reported A, B, and
      C electronic states, a new state denoted A' is identified with T0 = 20
      100.4090(16) cm-1 (63Cu2). Rotational analysis of the A'-X (0,0) and (1,0)
      transitions leads to the assignment of A' 1u. Ab initio calculations present the
      first theoretical description of the low energy states of the copper dimer in
      Hund's case (c) and confirm the experimental assignment. The discovery of this
      new low energy excited state emphasizes that spin-orbit coupling is significant
      in states with d-hole electronic configurations and resolves a decades-long
      mystery in the initial assignment of the A state.

PMID- 29221418
TI  - Optimizing the formation of colloidal compounds with components of different
      shapes.
AB  - By introducing favorable inter-species interactions, stoichiometric compound
      phases (C*), akin to intermetallic alloys, can be formed by binary mixtures of
      nanoparticle components of different shapes. The stability of such C* phases is
      expected to be affected by asymmetries in both the energetics of like vs. unlike
      species contacts, and the packing entropy of components, as captured by their
      shapes and relative sizes. Using Monte Carlo simulations, we explore the effect
      of changes in size ratio (for fixed contact energy) and in binding energy (for
      fixed size ratio) in the stability of the CsCl compound phase for equimolar
      mixtures of octahedra and spheres and of the NaCl compound for equimolar mixtures
      of cubes and spheres. As a general design rule, it is proposed that enhanced
      compound stability is associated with inter-species interactions that minimize
      the free-energy of the C* phase at coexistence with the (disordered) phase that
      is stable at lower concentrations. For the systems studied, this rule identifies
      optimal relative particle sizes and inter-species binding energies that are
      consistent with physically grounded expectations.

PMID- 29221417
TI  - L-edge spectroscopy of dilute, radiation-sensitive systems using a transition
      edge-sensor array.
AB  - We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering
      (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These
      measurements demonstrate the ability of high-throughput transition-edge-sensor
      (TES) spectrometers to access the rich soft X-ray (100-2000 eV) spectroscopy
      regime for dilute and radiation-sensitive samples. Our low-concentration data are
      in agreement with high-concentration measurements recorded by grating
      spectrometers. These results show that soft-X-ray RIXS spectroscopy acquired by
      high-throughput TES spectrometers can be used to study the local electronic
      structure of dilute metal-centered complexes relevant to biology, chemistry, and
      catalysis. In particular, TES spectrometers have a unique ability to characterize
      frozen solutions of radiation- and temperature-sensitive samples.

PMID- 29221419
TI  - Ionic solvation and solvent-solvent interaction effects on the charge and
      potential distributions in electric double layers.
AB  - Electric double layers are complex systems that involve a wide variety of
      interactions between the different components of the electrolyte solutions and
      with the charged interface. While the role of all Coulombic types of interactions
      is clear, that of the non-Coulombic forces is less obvious. The focus in the
      present study is on the effect of bulk solvation interactions on the properties
      of the electric double layer. The analysis is based on classical density
      functional theory. This approach allows us to account for the correlations
      between all charged (ionic) and uncharged (solvent) species in the solution. The
      surface charge at the boundary of the electric double layer is derived from the
      surface chemistry pertinent to the system. The surface is sensitive to the
      concentration of potential determining ions, which in turn depends on the
      correlations and activities of all remaining components. The analysis shows that
      the solvation forces have a profound effect on the charge and potential
      distributions in an electric double layer. This is true not just for the
      solvation of the potential determining ions, but for all species. Even varying
      the solvent-solvent interaction has a significant impact on the charge and
      potential distributions in the electric double layer.

PMID- 29221420
TI  - Influence of solvent polarization and non-uniform ion size on electrostatic
      properties between charged surfaces in an electrolyte solution.
AB  - In this paper, we study electrostatic properties between two similar or
      oppositely charged surfaces immersed in an electrolyte solution by using the mean
      field approach accounting for solvent polarization and non-uniform size effects.
      Applying a free energy formalism accounting for unequal ion sizes and
      orientational ordering of water dipoles, we derive coupled and self-consistent
      equations to calculate electrostatic properties between charged surfaces.
      Electrostatic properties for similarly charged surfaces depend on the counterion
      size but not on the coion size. Moreover, electrostatic potential and osmotic
      pressure between similarly charged surfaces are found to be increased with
      increasing counterion size. On the other hand, the corresponding ones between
      oppositely charged surfaces are related to both sizes of positive and negative
      ions. For oppositely charged surfaces, the electrostatic potential, number
      density of solvent molecules, and relative permittivity of an electrolyte having
      unequal ion sizes are not symmetric about the centerline between the charged
      surfaces. For either case, the consideration of solvent polarization results in a
      decrease in the electrostatic potential and the osmotic pressure compared to the
      case without the effect.

PMID- 29221421
TI  - A Qualitative Study of Latino Grandparents' Involvement in and Support for
      Grandchildren's Leisure Time Physical Activity.
AB  - BACKGROUND: Latino grandparents are often involved in rearing of grandchildren.
      However, their roles in promoting Latino children's leisure time physical
      activity (LTPA) have been largely overlooked by researchers. AIM: The purpose of
      this study is to examine Latino grandparents' involvement in and support for
      grandchildren's (age 2-12) LTPA as well as issues facing Latino grandparents.
      METHOD: Participants included 53 Latino grandparents who lived with/cared for or
      used to live with/care for grandchildren of 2 to 12 years old in three low-income
      areas of Los Angeles County. Data were collected using 4 semistructured focus
      groups and 26 semistructured interviews. Transcribed data were systematically and
      iteratively coded and analyzed. RESULTS: Latino grandparents perceived various
      benefits of physical activity to their grandchildren's physical and mental
      health, and supported grandchildren's LTPA directly and indirectly. The direct
      support included doing physical activity with grandchildren, taking grandchildren
      to places for physical activities, verbally asking grandchildren to do physical
      activities, and rewarding grandchildren for doing physical activities. The
      indirect support was made through providing suggestions to parents. Mothers
      usually regulated Latino grandparents' involvement in or support for
      grandchildren's LTPA and tended to promote a maternal lineage. Some Latino
      grandparents reported barriers to supporting grandchildren's LTPA, including lack
      of information, access to affordable and safe LTPA facilities/programs,
      transportation, money, and time. CONCLUSIONS: Latino grandparents are advocates
      for grandchildren's LTPA and support grandchildren's LTPA directly and
      indirectly. It may be promising to develop interventions to increase Latino
      grandparents' competency in supporting grandchildren's LTPA.

PMID- 29221423
TI  - Assess, Identify, Make it Happen (AIM) for Preschools: A Tool to Decrease Early
      Childhood Obesity.
AB  - Early childhood obesity is at epidemic proportions and is a major risk factor for
      the development of chronic diseases in adulthood. Since the majority of
      preschoolers are placed in center-based care, best practice policy, system, and
      environment (PSE) changes in early child care settings plays an important role in
      defining early development of obesogenic behaviors. However, implementation of
      best practice PSE changes is often a challenge in low resource settings due to
      staff turnover, time constraints, cultural beliefs, and lack of health-related
      knowledge. Assess, Identify, Make it Happen for Preschools (AIM-P) is a strategic
      planning process that was used with wellness teams in early child care centers to
      implement PSE changes that support adoption of health behaviors. AIM-P uses key
      change-making strategies based on intervention mapping including assets and needs
      assessments, prioritization of changes based on importance and feasibility,
      development of action steps and action plans, and identification of dissemination
      and sustainability plans. The AIM-P process resulted in implementation of 6.5
      best practice PSE changes per site. Qualitative findings highlight lessons
      learned and the facilitators and barriers associated with using AIM-P to
      implement PSEs.

PMID- 29221422
TI  - Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting
      the iRhom2/TACE signalling pathway activity in rats.
AB  - CONTEXT: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic
      (TFA) have been proven clinically effective at improving renal inflammation and
      glomerular injury in chronic kidney disease (CKD). OBJECTIVE: This study
      evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis
      factor-alpha converting enzyme) signalling and investigated its anti-DN (diabetic
      nephropathy) effects in a DN rat model. MATERIALS AND METHODS: In vitro, cells
      were treated with 200 MUg/mL advanced glycation end products (AGEs), and then co
      cultured with 20 MUg/mL TFA for 24 h. Real time PCR, western blotting and co
      immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old
      male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection
      of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at
      three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5
      mg/kg/d) was used as a positive control. RESULTS: IC50 of TFA is 35.6 MUM in HK2
      and 39.6 MUM in HRMC. TFA treatment (20 MUM) inhibited the activation of
      iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and
      ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the
      expression of proinflammatory cytokines and exerted anti-inflammatory effects
      significantly though inhibiting the activation of iRhom2/TACE signalling.
      DISCUSSION AND CONCLUSIONS: Our results show that TFA could dose-dependently
      ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE
      signalling and attenuating ER stress. These results suggest that TFA has
      potential therapeutic value for the treatment of DN in humans.

PMID- 29221424
TI  - Effects of dehydroepiandrosterone supplementation on mice with diminished ovarian
      reserve.
AB  - Dehydroepiandrosterone (DHEA) has been used to improve the pregnancy rate in
      women with diminished ovarian reserve(DOR) during in vitro fertilization. We
      aimed to validate the effects of DHEA and identify the possible mechanisms. We
      constructed a mice model with DOR and analyzed the hormone parameters and
      follicle counts. In vivo experiment, FSH and LH concentrations in the serum were
      significantly elevated in the DOR group. However, the FSH and LH concentrations
      were partially reversed in the DOR + DHEA group. The E2, AMH and INHB were down
      regulated in the DOR group and reversed in the DOR + DHEA group. Our study
      supported evidences that DHEA might modulate the hormone receptors in the ovary
      and hormone secretions to the peripheral circulation to regulate the ovary
      reserve functions.

PMID- 29221425
TI  - Riluzole does not improve lifespan or motor function in three ALS mouse models.
AB  - BACKGROUND: Riluzole is the most widespread therapeutic for treatment of the
      progressive degenerative disease amyotrophic lateral sclerosis (ALS). Riluzole
      gained FDA approval in 1995 before the development of ALS mouse models. We
      assessed riluzole in three transgenic ALS mouse models: the SOD1G93A model, the
      TDP-43A315T model, and the recently developed FUS (1-359) model. METHODS: Age,
      sex and litter-matched mice were treated with riluzole (22 mg/kg) in drinking
      water or vehicle (DMSO) from symptom onset. Lifespan was assessed and motor
      function tests were carried out twice weekly to determine whether riluzole slowed
      disease progression. RESULTS: Riluzole treatment had no significant benefit on
      lifespan in any of the ALS mouse models tested. Riluzole had no significant
      impact on decline in motor performance in the FUS (1-359) and SOD1G93A transgenic
      mice as assessed by Rotarod and stride length analysis. CONCLUSIONS: Riluzole is
      widely prescribed for ALS patients despite questions surrounding its efficacy.
      Our data suggest that if riluzole was identified as a therapeutic candidate today
      it would not progress past pre-clinical assessment. This raises questions about
      the standards used in pre-clinical assessment of therapeutic candidates for the
      treatment of ALS.

PMID- 29221426
TI  - Enterogenous cyst of the small bowel mesentery: a case report and review of the
      literature.
AB  - INTRODUCTION: Enterogenous cysts are a very rare congenital abnormality that can
      be found anywhere within the gastrointestinal tract, most commonly in the small
      intestine. The incidence is approximately one in 4500-10,000 live births.
      Diagnosis can be suggested by ultrasound (US), computed tomography (CT) scans or
      magnetic resonance imaging (MRI) findings, although histological examination
      confirms the definitive diagnosis. PATIENTS: We present a case of enterogenous
      cyst in an adult female who underwent a resection of the tumour. RESULTS: After
      two years of observation, there is no evidence of tumour recurrence.

PMID- 29221427
TI  - Validity of the Dutch modified painDETECT questionnaire for patients with hip or
      knee osteoarthritis.
AB  - BACKGROUND: The modified painDETECT questionnaire (PDQ) is a self-reported
      questionnaire to discriminate between nociceptive and neuropathic-like pain in
      patients with knee/hip osteoarthritis (OA). This study aims to assess the
      structural and construct validity of this questionnaire. METHODS: Confirmatory
      factor analysis and hypothesis-testing was used. For 168 patients, predefined
      hypotheses were formulated on the correlation between the modified painDETECT and
      several other questionnaires, and in a subsample of 46 with pain pressure
      thresholds (PPTs). RESULTS: Two principal components were confirmed. The pain
      pattern item did not load on any component. Eighty per cent of the hypotheses on
      the correlation between modified PDQ and the questionnaires were met, as were 50%
      concerning PPTs measurements. CONCLUSIONS: This study is the first to assess
      structural and construct validity of the modified PDQ knee/hip by using factor
      analysis and hypothesis-testing. This questionnaire seems to reflect neuropathic
      like pain symptoms experienced by hip/knee OA-patients with adequate validity.
      The item on pain pattern might not reflect the construct. More than 75% of the
      predefined hypotheses regarding the modified PDQ and the other questionnaires
      were met. Only 50% of the hypotheses on PPTs measurements were met, probably due
      to heterogeneity and limited size of this subsample. Implications for
      rehabilitation Pain in osteoarthritis (OA) is partly caused by modification of
      pain transmission in the peripheral and central nervous system, leading to
      sensitisation. This process seems particularly significant in a subgroup of OA
      patients. Sensitisation in OA is associated with more disability in daily life,
      lower quality of life and more widespread pain, as well as poorer outcome of
      total joint surgery. Screening for sensitisation can help to identify the
      subgroup of patients who could benefit from multidisciplinary treatment options
      focussing on desensitisation, cognitive- and behavioural therapy and reducing
      chronification of widespread pain. Therefore, being particularly important in the
      field of rehabilitation. The Dutch modified PainDETECT-questionnaire is very
      useful for rehabilitation professionals as it is one of the first questionnaires
      specifically validated to assess neuropathic-like symptoms (indicating
      sensitisation) in patients with knee or hip osteoarthritis.

PMID- 29221428
TI  - Interactions between stereotype threat, subjective aging, and memory in older
      adults.
AB  - This study examined whether the effects of stereotype threat on memory and
      subjective age were moderated by positive age stereotypes and self-perceptions of
      aging among older adults. Perceived threat as a mechanism underlying these
      effects was also explored. Results showed that stereotype threat (high vs. low
      threat) did not affect the dependent variables. Moreover, self-perceptions of
      aging did not moderate the effect of stereotype threat on the dependent
      variables. However, for people with more positive age stereotypes, older people
      under highthreat perceived more threat than people under low threat. This could
      be explained by an effect of age stereotypes in the high-threat group: the more
      positive age stereotypes held by participants, the more they perceived threat,
      which in turn decreased their memory performance and made them feel mentally
      older. We hypothesized that age group identity is stronger in people with more
      positive age stereotypes, which increase perceived threat.

PMID- 29221429
TI  - Measuring inter-leg difference to diagnose peripheral artery disease?

PMID- 29221430
TI  - The study of intravitreal drug pharmacokinetics: does it matter? and if so, how?

PMID- 29221431
TI  - The Role of Primary Care Providers in Encouraging Older Patients to Change Their
      Lifestyle Behaviors.
AB  - OBJECTIVES: This study sought to identify older patients' perceptions of primary
      care providers' influence on their likelihood of improving diet and physical
      activity. METHODS: 104 adults ages 65 and older were interviewed immediately
      following a routine primary care visit about their plans and motivations for
      behavior change and how their clinic visit would influence their likelihood of
      making lifestyle changes. All interviews were recorded, transcribed and analyzed
      using a constant comparison approach. RESULTS: Participants reported that their
      providers influence their health behaviors by developing strong relationships,
      addressing concerns and encouraging change, and providing concrete instruction.
      When providers did not discuss diet or physical activity, or mentioned these
      topics only briefly, participants often perceived the message that they should
      continue their current behaviors. CONCLUSIONS: Whether and how diet and physical
      activity are discussed in primary care influences the likelihood that older
      adults will make changes in these behaviors. CLINICAL IMPLICATIONS: These
      findings highlight the need for a patient-centered counseling approach and
      caution providers to think twice before omitting discussion of the need for
      lifestyle change.

PMID- 29221432
TI  - Sex and ethnic/racial-specific risk factors for gallbladder disease.
AB  - BACKGROUND: Gallbladder disease (GBD) is a highly prevalent condition; however,
      little is known about potential differences in risk factors by sex and
      ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related
      factors and GBD in multiethnic populations. METHODS: We performed a prospective
      analysis from the Multiethnic Cohort study who self-identified as non-Hispanic
      White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native
      Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using
      Medicare and California hospital discharge files (1993-2012) and self-completed
      questionnaires. We used exposure information on the baseline questionnaire to
      identify exposures of interest. Associations were estimated by hazard ratios and
      95% confidence intervals using Cox models adjusted for confounders. RESULT: After
      a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m2,
      diabetes, past and current smoking, red meat consumption, saturated fat and
      cholesterol were significant risk factors across ethnic/racial populations (p
      trends < 0.01). Protective factors included vigorous physical activity, alcohol
      use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01).
      Carbohydrates were inversely associated with GBD risk only among women and
      Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant
      risk factor among women; post-menopausal hormones use was only associated with an
      increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43
      and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42). CONCLUSION: Overall,
      dietary, reproductive and obesity-related factors are strong risk factors for GBD
      affecting men and women of different ethnicities/races; however some risk factors
      appear stronger in women and certain ethnic groups.

PMID- 29221433
TI  - Hyporesponsiveness of natural killer cells and impaired inflammatory responses in
      critically ill patients.
AB  - BACKGROUND: To investigate natural killer (NK) cell activity, circulating
      cytokine level and peripheral blood mononuclear cell (PBMC) cytokine production
      status in critically ill patients. METHODS: Blood samples were collected <24 h
      after admission from 24 intensive care unit (ICU) patients and 24 age-, sex-, and
      body mass index (BMI)-matched healthy controls. Serum cytokine concentrations and
      cytokine production by PBMCs and lipopolysaccharide (LPS)-stimulated PBMCs were
      measured. RESULTS: The ICU group showed lower NK cell activity than the controls
      under all conditions and an absence of interferon (IFN)-gamma. After adjusting
      for triglycerides, LDL- and HDL-cholesterol, and glucose, the ICU group exhibited
      lower serum levels of albumin and interleukin (IL)-12 and higher leukocyte counts
      and hs-CRP and IL-6 levels than the controls. Non-stimulated PBMCs from ICU
      patients secreted significantly greater amounts of IL-6 and IL-1beta than the
      controls; however, the production of IL-6, TNF-alpha and IL-1beta in response to
      LPS stimulation was significantly lower in the ICU group. CONCLUSIONS:
      Significant reductions in NK cell activity and serum IL-12 level, an absence of
      serum IFN-gamma, and decreased cytokine production from LPS-stimulated PBMCs
      indicate the hyporesponsiveness of NK cells and an impaired early phase
      inflammatory response in critically ill patients (ClinicalTrials.gov NCT02565589
      :). Retrospectively registered; October 1, 2015.

PMID- 29221434
TI  - Longitudinal drop-out and weighting against its bias.
AB  - BACKGROUND: The bias caused by drop-out is an important factor in large
      population-based epidemiological studies. Many studies account for it by
      weighting their longitudinal data, but to date there is no detailed final
      approach for how to conduct these weights. METHODS: In this study we describe the
      observed longitudinal bias and a three-step longitudinal weighting approach used
      for the longitudinal data in the MoMo baseline (N = 4528, 4-17 years) and wave 1
      study with 2807 (62%) participants between 2003 and 2012. RESULTS: The most
      meaningful drop-out predictors were socioeconomic status of the household,
      socioeconomic characteristics of the mother and daily TV usage. Weighting reduced
      the bias between the longitudinal participants and the baseline sample, and also
      increased variance by 5% to 35% with a final weighting efficiency of 41.67%.
      CONCLUSIONS: We conclude that a weighting procedure is important to reduce
      longitudinal bias in health-oriented epidemiological studies and suggest
      identifying the most influencing variables in the first step, then use logistic
      regression modeling to calculate the inverse of the probability of participation
      in the second step, and finally trim and standardize the weights in the third
      step.

PMID- 29221435
TI  - Exploring digenic inheritance in arrhythmogenic cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder,
      characterized by the substitution of heart muscle with fibro-fatty tissue and
      severe ventricular arrhythmias, often leading to heart failure and sudden cardiac
      death. ACM is considered a monogenic disorder, but the low penetrance of
      mutations identified in patients suggests the involvement of additional genetic
      or environmental factors. METHODS: We used whole exome sequencing to investigate
      digenic inheritance in two ACM families where previous diagnostic tests have
      revealed a PKP2 mutation in all affected and some healthy individuals. In family
      members with PKP2 mutations we determined all genes that harbor variants in
      affected but not in healthy carriers or vice versa. We computationally
      prioritized the most likely candidates, focusing on known ACM genes and genes
      related to PKP2 through protein interactions, functional relationships, or shared
      biological processes. RESULTS: We identified four candidate genes in family 1,
      namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The
      most promising gene in the second family is TTN, a gene previously associated
      with ACM, in which the affected individual harbors two rare deleterious-predicted
      missense variants, one of which is located in the protein's only serine kinase
      domain. CONCLUSIONS: In this study we report genes that might act as digenic
      players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations.
      Validation in larger cohorts is still required to prove the utility of this
      model.

PMID- 29221436
TI  - Prevalence and related risk factors of chronic kidney disease among adults in
      Luxembourg: evidence from the observation of cardiovascular risk factors (ORISCAV
      LUX) study.
AB  - BACKGROUND: Evidence on stages of renal impairment and related risk factors in
      Luxembourg is lacking. This study aimed to assess the prevalence of chronic
      kidney disease (CKD) and identify potential correlates among the general
      population, using the recent definition suggested by the Kidney Disease Improving
      Global Outcomes guidelines. METHODS: Data analysed from 1361 participants aged 18
      69 years, enrolled in the Observation of Cardiovascular Risk Factors in
      Luxembourg (ORISCAV-LUX) study, 2007-08. Descriptive and multivariable logistic
      regression analyses were performed to identify demographic, socio-economic,
      behavioural, and clinical factors associated with CKD, defined as a single
      estimated glomerular filtration rate (eGFR) measure <60 ml/min/1.73m2 and/or
      urinary albumin: creatinine ratio (ACR) > 30 mg/g. RESULTS: Overall, 6.3% had
      CKD, including 4.4% and 0.7% with moderate and severe macroalbuminuria
      respectively. 0.1% had kidney failure (eGFR < 15 ml/min/1.73 m2). CKD was higher
      among subjects with primary education and risk increased significantly with age;
      the odd ratio was more than 2-fold higher among participants aged 50-69 years.
      Hypertension and diabetes were associated with more than 3-fold and 4-fold higher
      risks of CKD [adjusted odd ratio (AOR 3.46 (95%CI 1.92, 6.24), P < 0.001] and
      [AOR 4.45 (2.18, 9.07), P < 0.001] respectively. Increased physical activity
      measured as total MET-hour/week was independently associated with a lower odds of
      CKD (P = 0.035). CONCLUSION: The national baseline prevalence estimate of CKD, a
      neglected public health problem, stresses the benefit of early detection
      particularly in high-risk subjects with associated cardiovascular pathologies
      (e.g. hypertension, diabetes), to prevent and defray costs related to eventual
      complications.

PMID- 29221437
TI  - Evolutionary characterization and transcript profiling of beta-tubulin genes in
      flax (Linum usitatissimum L.) during plant development.
AB  - BACKGROUND: Microtubules, polymerized from alpha and beta-tubulin monomers, play
      a fundamental role in plant morphogenesis, determining the cell division plane,
      the direction of cell expansion and the deposition of cell wall material. During
      polarized pollen tube elongation, microtubules serve as tracks for vesicular
      transport and deposition of proteins/lipids at the tip membrane. Such functions
      are controlled by cortical microtubule arrays. Aim of this study was to first
      characterize the flax beta-tubulin family by sequence and phylogenetic analysis
      and to investigate differential expression of beta-tubulin genes possibly related
      to fibre elongation and to flower development. RESULTS: We report the cloning and
      characterization of the complete flax beta-tubulin gene family: exon-intron
      organization, duplicated gene comparison, phylogenetic analysis and expression
      pattern during stem and hypocotyl elongation and during flower development.
      Sequence analysis of the fourteen expressed beta-tubulin genes revealed that the
      recent whole genome duplication of the flax genome was followed by massive
      retention of duplicated tubulin genes. Expression analysis showed that beta
      tubulin mRNA profiles gradually changed along with phloem fibre development in
      both the stem and hypocotyl. In flowers, changes in relative tubulin transcript
      levels took place at anthesis in anthers, but not in carpels. CONCLUSIONS:
      Phylogenetic analysis supports the origin of extant plant beta-tubulin genes from
      four ancestral genes pre-dating angiosperm separation. Expression analysis
      suggests that particular tubulin subpopulations are more suitable to sustain
      different microtubule functions such as cell elongation, cell wall thickening or
      pollen tube growth. Tubulin genes possibly related to different microtubule
      functions were identified as candidate for more detailed studies.

PMID- 29221438
TI  - Double-catheter lavage combined with percutaneous flexible endoscopic debridement
      for infected pancreatic necrosis failed to percutaneous catheter drainage.
AB  - BACKGROUND: Infected pancreatic necrosis (IPN) is a serious local complication of
      acute pancreatitis, with high mortality. Minimally invasive therapy including
      percutaneous catheter drainage (PCD) has become the preferred method for IPN
      instead of traditional open necrosectomy. However, the efficacy of double
      catheter lavage in combination with percutaneous flexible endoscopic debridement
      after PCD failure is unknown compared with surgical necrosectomy. METHODS: A
      total of 27 cases of IPN patients with failure PCD between Jan 2014 and Dec 2015
      were enrolled in this retrospective cohort study. Fifteen patients received
      double-catheter lavage in combination with percutaneous flexible endoscopic
      debridement, and 12 patients underwent open necrosectomy. The primary endpoint
      was the composite end point of major complications or death. The secondary
      endpoint included mortality, major complication rate, ICU admission length of
      stay, and overall length of stay. RESULTS: The primary endpoint occurrence rate
      in double-catheter lavage in combination with percutaneous flexible endoscopic
      debridement group (8/15, 53%) was significantly lower than that in open
      necrosectomy group (11/12, 92%) (RR = 1.71, 95% CI = 1.04 - 2.84, P < 0.05).
      Though the mortality between two groups showed no statistical significance (0%
      vs. 17%, P = 0.19), the rate of new-onset multiple organ failure and ICU
      admission length of stay in the experimental group was significantly lower than
      that in open necrosectomy group (13% vs. 58%, P = 0.04; 0 vs. 17, P = 0.02,
      respectively). Only 40% of patients required ICU admission after percutaneous
      debridement, which was markedly lower than the patients who underwent surgery
      (83%; P < 0.05). CONCLUSIONS: Double-catheter lavage in combination with
      percutaneous flexible endoscopic debridement showed superior effectiveness,
      safety, and convenience in patients with IPN after PCD failure as compared to
      open necrosectomy.

PMID- 29221439
TI  - Catheter-related blood stream infections in hemodialysis patients: a prospective
      cohort study.
AB  - BACKGROUND: For people requiring hemodialysis, infectious mortality is
      independently associated with geographic distance from a nephrologist. We aimed
      to determine if differential management of catheter-related blood stream
      infections (CRBSIs) could explain poorer outcomes. METHODS: We prospectively
      collected data from adults initiating hemodialysis with a central venous catheter
      between 2005 and 2015 in Alberta, Canada. We collected indicators of CRBSI
      management (timely catheter removal, relapsing bacteremia); frequency of CRBSIs;
      hospitalizations; predictors of CRBSIs, and bacteremia. We evaluated indicators
      and infectious episodes as a function of the shortest distance by road to the
      closest nephrologist's practice: <50 (referent); 50-99; and >=100 km. RESULTS:
      One thousand one hundred thirty-one participants were followed for a median of
      755 days (interquartile range (IQR) 219, 1465) and used dialysis catheters for a
      median of 565 days (IQR 176, 1288). Compared to the referent group, there was no
      significant difference in the rate ratio (RR) of CRBSI in the 50-100 and >100 km
      distance categories: RR 1.63; 95% confidence interval (CI) (0.91, 2.91); RR 0.84
      (95% CI 0.44, 1.58); p = 0.87, respectively or in bacteremia: RR 1.42; (95% CI
      0.83, 2.45); RR 0.79 (95% CI 0.45,1.39) p = 0.74, respectively. There were no
      differences in indicators of appropriate CRBSI management or hospitalizations
      according to distance. The overall incidence of CRBSIs was low (0.19 per 1000
      catheter days) as was the frequency of relapse. Only liver disease was
      independently associated with CRBSI (RR 2.11; 95% CI 1.15, 3.86). CONCLUSIONS:
      The frequency and management of CRBSIs did not differ by location; however, event
      rates were low.

PMID- 29221440
TI  - Effect of flecainide on atrial fibrillatory rate in a large animal model with
      induced atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillatory cycle length has been considered one of the
      indices of atrial electrical remodelling during atrial fibrillation (AF), which
      can be assessed from surface ECG by computer-assisted calculation of atrial
      fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF
      studies since horses too, develop lone AF, however data on AF characteristics in
      horses are extremely sparse and non-invasive characterization of AF complexity
      using surface ECG processing has not been reported. AIM: The aim was to study
      characteristics of induced AF and its modification by flecainide. METHODS: The
      study group consisted on 3 horses with spontaneous persistent AF and 13 with pace
      induced AF. Seven horses were treated with saline (control) and eight with
      flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of
      QRST complexes and calculation of AFR from the residual atrial signal. RESULTS:
      At AF onset, AFR was 295 +/- 52 fibrillations per minute (fpm) in the horses with
      induced AF treated with flecainide, 269 +/- 36 fpm in the control group (ns), and
      364 +/- 26 fpm in the horses with spontaneous persistent AF (P < 0.05 compared to
      the control group). Flecainide caused a decrease in AFR in all animals and
      restored sinus rhythm in the animals with induced AF. In the control animals, AFR
      increased from 269 +/- 36 fpm to a plateau of 313 +/- 14 fpm before decreasing to
      288 +/- 28 fpm during the last 10% of the AF episodes preceding spontaneous
      conversion (P < 0.05). CONCLUSION: AFR in horses with induced AF resembles AFR in
      humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all
      horses, further supporting the method to be a non-invasive technique to study the
      effect of antiarrhythmic compounds.

PMID- 29221441
TI  - Time-varying serum gradient of hepatitis B surface antigen predicts risk of
      relapses after off-NA therapy.
AB  - BACKGROUND: The serum gradient of hepatitis B surface antigen (HBsAg) varies over
      time after cessation of nucleos(t)ide analog (NA) treatment in patients with
      chronic hepatitis B (CHB). The association between the time-varying HBsAg serum
      gradient and risk of relapse has not been elucidated. METHODS: This multicenter
      cohort study prospectively enrolled CHB patients who discontinued 3 year-NA
      treatment. Eligible patients were serologically negative for HBeAg and viral DNA
      at NA cessation. The participants (n = 140) were followed every 3 months through
      HBsAg quantification. Virological and clinical relapses were defined as viral DNA
      levels >2000 IU/mL and alanine aminotransferase (ALT) levels >80 U/mL,
      respectively. The association of time-varying HBsAg levels with relapses was
      assessed through a time-dependent Cox analysis. RESULTS: During a median follow
      up of 19.9 (interquartile range [IQR], 10.6-25.3) months, virological and
      clinical relapses occurred in 94 and 49 patients, with a 2-year cumulative
      incidence of 79.2% (95% confidence interval [CI], 70.9%-86.4%) and 42.9% (95% CI,
      34.1%-52.8%), respectively. The serum level of HBsAg was associated with
      virological (P < 0.001) and clinical (P = 0.01) relapses in a dose-response
      manner, with adjusted hazard ratios of 2.10 (95% CI, 1.45-3.04) and 2.32 (95% CI,
      1.28-4.21). Among the patients (n = 19) whose HBsAg levels ever dropped below 10
      IU/mL, only one and three patients subsequently developed clinical and
      virological relapses. CONCLUSION: The serum gradient of HBsAg measured throughout
      the off-therapy observation is associated with the subsequent occurrence of
      virological and clinical relapses in CHB patients who discontinue NA treatment.

PMID- 29221442
TI  - General practitioners' awareness of depressive symptomatology is not associated
      with quality of life in heart failure patients - cross-sectional results of the
      observational RECODE-HF Study.
AB  - BACKGROUND: Depression is a common comorbidity in patients with chronic heart
      failure (HF) and linked to a wider range of symptoms which, in turn, are linked
      to a decreased health-related quality of life (HRQOL). Treatment of depression
      might improve HRQOL but detecting depression is difficult due to the symptom
      overlap between HF and depression. Therefore, clinical guidelines recommend to
      routinely screen for depression in HF patients. No studies have so far
      investigated the treatment after getting aware of a depressive symptomatology and
      its correlation with HRQOL in primary care HF patients. Therefore, we examined
      the factors linked to depression treatment and those linked to HRQOL in HF
      patients. We hypothesized that GPs' awareness of depressive symptomatology was
      associated with depression treatment and HRQOL in HF patients. METHODS: For this
      observational study, HF patients were recruited in primary care practices and
      filled out a questionnaire including PHQ-9 and HADS. A total of 574 patients
      screened positive for depressive symptomatology. Their GPs were interviewed by
      phone regarding the patients' comorbidities and potential depression treatment.
      Descriptive and regression analysis were performed. RESULTS: GPs reported various
      types of depression treatments (including dialogue/counselling by the GP
      him/herself in 31.8% of the patients). The reported rates differed considerably
      between GP-reported initiated treatment and patient-reported utilised treatment
      regarding psychotherapy (16.4% vs. 9.5%) and pharmacotherapy (61.2% vs. 30.3%).
      The GPs' awareness of depressive symptomatology was significantly associated with
      the likelihood of receiving pharmacotherapy (OR 2.8; p < 0.001) but not
      psychotherapy. The patient's HRQOL was not significantly associated with the GPs'
      awareness of depression. CONCLUSION: GPs should be aware of the gap between GP
      initiated and patient-utilised depression treatments in patients with chronic HF,
      which might lead to an undersupply of depression treatment. It remains to be
      investigated why GPs' awareness of depressive symptomatology is not linked to
      patients' HRQOL. We hypothesize that GPs are aware of cases with reduced HRQOL
      (which improves under depression treatment) and unaware of cases whose depression
      do not significantly impair HRQOL, resulting in comparable levels of HRQOL in
      both groups. This hypothesis needs to be further investigated.

PMID- 29221443
TI  - Diverse effects of distance cutoff and residue interval on the performance of
      distance-dependent atom-pair potential in protein structure prediction.
AB  - BACKGROUND: As one of the most successful knowledge-based energy functions, the
      distance-dependent atom-pair potential is widely used in all aspects of protein
      structure prediction, including conformational search, model refinement, and
      model assessment. During the last two decades, great efforts have been made to
      improve the reference state of the potential, while other factors that also
      strongly affect the performance of the potential have been relatively less
      investigated. RESULTS: Based on different distance cutoffs (from 5 to 22 A) and
      residue intervals (from 0 to 15) as well as six different reference states, we
      constructed a series of distance-dependent atom-pair potentials and tested them
      on several groups of structural decoy sets collected from diverse sources. A
      comprehensive investigation has been performed to clarify the effects of distance
      cutoff and residue interval on the potential's performance. Our results provide a
      new perspective as well as a practical guidance for optimizing distance-dependent
      statistical potentials. CONCLUSIONS: The optimal distance cutoff and residue
      interval are highly related with the reference state that the potential is based
      on, the measurements of the potential's performance, and the decoy sets that the
      potential is applied to. The performance of distance-dependent statistical
      potential can be significantly improved when the best statistical parameters for
      the specific application environment are adopted.

PMID- 29221445
TI  - Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined
      chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to
      patients with advanced gastric cancer.
AB  - BACKGROUND: In Japan, S-1 plus cisplatin (SP) regimen has become a standard
      therapy for patients with advanced gastric cancer. Moreover, the S-1 plus
      oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for
      chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel,
      created with albumin-bound paclitaxel particles, has high transferability to
      tumour tissues and does not cause hypersensitivity reactions because of a
      different chemical composition compared with docetaxel and paclitaxel. A
      combination of S-1, nab-paclitaxel and oxaliplatin (which we named 'SNOW
      regimen') can be a promising triplet therapy for advanced gastric cancer.
      Although we have to pay attention to chemotherapy-induced neuropathy, we aim to
      investigate the recommended dose of this regimen in a phase I study. Furthermore,
      we will investigate its efficacy and toxicity in a phase II study. METHODS: The
      phase I study is a dose-escalation study using a standard 3 plus 3 design,
      followed by expansion cohorts. The SNOW regimen involves 28-day cycles with
      escalated doses of nab-paclitaxel (100-175 mg/m2 on days 1 and 15) and fixed
      doses of oxaliplatin (65 mg/ m2 on days 1 and 15) and S-1 (80 mg/m2/day on day 1
      to 14). The primary endpoints are assessment of dose limiting toxicities and
      determination of maximum tolerated dose to investigate the recommended dose in
      the subsequent phase II study. In the phase II study, the primary endpoint is
      objective response rate. Secondary endpoints are assessment of safety,
      progression-free survival, disease control rate, overall survival and time to
      treatment failure. Adverse events were monitored and graded according to the
      National Cancer Institute Common Terminology Criteria for Adverse Events version
      4.0. DISCUSSION: Triplet therapies for advanced gastric cancer patients have been
      evaluated in clinical trials. The SNOW regimen can be a promising new triplet
      therapy. TRIAL REGISTRATION: This study is performed at institutes that
      participate in Hokkaido Gastrointestinal Cancer Study Group (HGCSG) and
      registered as UMIN000016788 . Registrated 16 March 2015.

PMID- 29221444
TI  - Genome-wide association study of coronary artery calcified atherosclerotic plaque
      in African Americans with type 2 diabetes.
AB  - BACKGROUND: Coronary artery calcified atherosclerotic plaque (CAC) predicts
      cardiovascular disease (CVD). Despite exposure to more severe conventional CVD
      risk factors, African Americans (AAs) are less likely to develop CAC, and when
      they do, have markedly lower levels than European Americans. Genetic factors
      likely contribute to the observed ethnic differences. To identify genes
      associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association
      study (GWAS) was performed using the Illumina 5 M chip in 691 African American
      Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart
      Study (JHS) participants with T2D. Genetic association tests were performed on
      the genotyped and 1000 Genomes-imputed markers separately for each study, and
      combined in a meta-analysis. RESULTS: Single nucleotide polymorphisms (SNPs),
      rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825
      (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623
      (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and
      JHS, with meta-analysis p-values <=8.0 * 10-7. The strongest result in AA-DHS
      alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = -1.14
      (0.20); p-value = 9.1 * 10-9). This GWAS peak replicated a previously reported AA
      DHS CAC admixture signal (rs7492028, LOD score 2.8). CONCLUSIONS: Genetic
      association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were
      detected in AAs with T2D from AA-DHS and replicated in the JHS. These data
      support a role for genetic variation on these chromosomes as contributors to CAC
      in AAs with T2D, as well as to variation in CAC between populations of African
      and European ancestry.

PMID- 29221446
TI  - A systematic review of test accuracy studies evaluating molecular micro-satellite
      instability testing for the detection of individuals with lynch syndrome.
AB  - BACKGROUND: A systematic review was conducted to assess the diagnostic test
      accuracy of polymerase chain reaction (PCR)-based microsatellite instability
      (MSI) testing for identifying Lynch syndrome in patients with colorectal cancer
      (CRC). Unlike previous reviews, this was based on assessing MSI testing against
      best practice for the reference standard, and included CRC populations that were
      unselected, age-limited or high-risk for Lynch syndrome. METHODS: Single- and two
      gate diagnostic test accuracy studies, or similar, were identified, assessed for
      inclusion, data extracted and quality appraised by two reviewers according to a
      pre-specified protocol. Sensitivity of MSI testing was estimated for all included
      studies. Specificity, likelihood ratios and predictive values were estimated for
      studies that were not based on high-risk samples. Narrative synthesis was
      conducted. RESULTS: Nine study samples were included. When MSI-Low results were
      considered to be negative, sensitivity estimates ranged from 67% (95% CI 47, 83)
      to 100% (95% CI 94, 100). Three studies contributed to estimates of both
      sensitivity and specificity, with specificity ranging from 61% (95% CI 57, 65),
      to 93% (95% CI 89, 95). Good sensitivity was achieved at the expense of
      specificity. When MSI-L was considered to be positive (effectively lowering the
      threshold for a positive index test result) sensitivity increased and specificity
      decreased. Between-study heterogeneity in both the MSI and reference standard
      testing, combined with the low number of studies contributing to both sensitivity
      and specificity estimates, precluded pooling by meta-analysis. CONCLUSIONS: MSI
      testing is an effective screening test for Lynch syndrome. However, there is
      significant uncertainty surrounding what balance of sensitivity and specificity
      will be achieved in clinical practice and how this relates to specific
      characteristics of the test (such as the panel of markers used or the thresholds
      used to denote a positive test).

PMID- 29221447
TI  - Disruption of postnatal folliculogenesis and development of ovarian tumor in a
      mouse model with aberrant transforming growth factor beta signaling.
AB  - BACKGROUND: Transforming growth factor beta (TGFB) superfamily signaling is
      implicated in the development of sex cord-stromal tumors, a category of poorly
      defined gonadal tumors. The aim of this study was to determine potential effects
      of dysregulated TGFB signaling in the ovary using Cre recombinase driven by
      growth differentiation factor 9 (Gdf9) promoter known to be expressed in oocytes.
      METHODS: A mouse model containing constitutively active TGFBR1 (TGFBR1CA) using
      Gdf9-iCre (termed TGFBR1-CAG9Cre) was generated. Hematoxylin and eosin (H & E)
      staining, follicle counting, and immunohistochemistry and immunofluorescence
      analyses using antibodies directed to Ki67, forkhead box L2 (FOXL2), forkhead box
      O1 (FOXO1), inhibin alpha (INHA), and SRY (sex determining region Y)-box 9 were
      performed to determine the characteristics of the TGFBR1-CAG9Cre ovary. Terminal
      deoxynucleotidyl transferase (TdT) labeling of 3'-OH ends of DNA fragments, real
      time PCR, and western blotting were used to examine apoptosis, select gene
      expression, and TGFBR1 activation. RNAscope in situ hybridization was used to
      localize the expression of GLI-Kruppel family member GLI1 (Gli1) in ovarian tumor
      tissues. RESULTS: TGFBR1-CAG9Cre females were sterile. Sustained activation of
      TGFBR1 led to altered granulosa cell proliferation evidenced by high expression
      of Ki67. At an early age, these mice demonstrated follicular defects and
      development of ovarian granulosa cell tumors, which were immunoreactive for
      granulosa cell markers including FOXL2, FOXO1, and INHA. Further histochemical
      and molecular analyses provided evidence of overactivation of TGFBR1 in the
      granulosa cell compartment during ovarian pathogenesis in TGFBR1-CAG9Cre mice,
      along with upregulation of Gli1 and Gli2 and downregulation of Tgfbr3 in ovarian
      tumor tissues. CONCLUSIONS: These results reinforce the role of constitutively
      active TGFBR1 in promoting ovarian tumorigenesis in mice. The mouse model created
      in this study may be further exploited to define the cellular and molecular
      mechanisms of TGFB/activin downstream signaling in granulosa cell tumor
      development. Future studies are needed to test whether activation of TGFB/activin
      signaling contributes to the development of human granulosa cell tumors.

PMID- 29221448
TI  - Next-generation sequencing: recent applications to the analysis of colorectal
      cancer.
AB  - Since the establishment of the Sanger sequencing method, scientists around the
      world focused their efforts to progress in the field to produce the utmost
      technology. The introduction of next-generation sequencing (NGS) represents a
      revolutionary step and promises to lead to massive improvements in our
      understanding on the role of nucleic acids functions. Cancer research began to
      use this innovative and highly performing method, and interesting results started
      to appear in colorectal cancer (CRC) analysis. Several studies produced high
      quality data in terms of mutation discovery, especially about actionable or less
      frequently mutated genes, epigenetics, transcriptomics. Analysis of results is
      unveiling relevant perspectives aiding to evaluate the response to therapies.
      Novel evidences have been presented also in other directions such as gut
      microbiota or CRC circulating tumor cells. However, despite its unquestioned
      potential, NGS poses some issues calling for additional studies. This review
      intends to offer a view of the state of the art of NGS applications to CRC
      through examination of the most important technologies and discussion of recent
      published results.

PMID- 29221450
TI  - Peer feedback for examiner quality assurance on MRCGP International South Asia: a
      mixed methods study.
AB  - BACKGROUND: The International Membership Examination (MRCGP[INT]) of the Royal
      College of General Practitioners UK is a unique collaboration between four South
      Asian countries with diverse cultures, epidemiology, clinical facilities and
      resources. In this setting good quality assurance is imperative to achieve
      acceptable standards of inter rater reliability. This study aims to explore the
      process of peer feedback for examiner quality assurance with regard to factors
      affecting the implementation and acceptance of the method. METHODS: A sequential
      mixed methods approach was used based on focus group discussions with examiners
      (n = 12) and clinical examination convenors who acted as peer reviewers (n = 4).
      A questionnaire based on emerging themes and literature review was then completed
      by 20 examiners at the subsequent OSCE exam. Qualitative data were analysed using
      an iterative reflexive process. Quantitative data were integrated by interpretive
      analysis looking for convergence, complementarity or dissonance. The qualitative
      data helped understand the issues and informed the process of developing the
      questionnaire. The quantitative data allowed for further refining of issues,
      wider sampling of examiners and giving voice to different perspectives. RESULTS:
      Examiners stated specifically that peer feedback gave an opportunity for
      discussion, standardisation of judgments and improved discriminatory abilities.
      Interpersonal dynamics, hierarchy and perception of validity of feedback were
      major factors influencing acceptance of feedback. Examiners desired increased
      transparency, accountability and the opportunity for equal partnership within the
      process. The process was stressful for examiners and reviewers; however
      acceptance increased with increasing exposure to receiving feedback. The process
      could be refined to improve acceptability through scrupulous attention to
      training and selection of those giving feedback to improve the perceived validity
      of feedback and improved reviewer feedback skills to enable better interpersonal
      dynamics and a more equitable feedback process. It is important to highlight the
      role of quality assurance and peer feedback as a tool for continuous improvement
      and maintenance of standards to examiners during training. CONCLUSION: Examiner
      quality assurance using peer feedback was generally a successful and accepted
      process. The findings highlight areas for improvement and guide the path towards
      a model of feedback that is responsive to examiner views and cultural
      sensibilities.

PMID- 29221449
TI  - Changes in physical activity during the retirement transition: a series of novel
      n-of-1 natural experiments.
AB  - BACKGROUND: Existing evidence about the impact of retirement on physical activity
      (PA) has primarily focused on the average change in PA level after retirement in
      group-based studies. It is unclear whether findings regarding the direction of PA
      change after retirement from group-based studies apply to individuals. This study
      aimed to explore changes in PA, PA determinants and their inter-relationships
      during the retirement transition at the individual level. METHODS: A series of n
      of-1 natural experiments were conducted with seven individuals who were aged 55
      76 years and approaching retirement. PA was measured by tri-axial accelerometry.
      Twice-daily self-report and ecological momentary assessments of evidence- and
      theory-based determinants of PA (e.g. sleep length/quality, happiness, tiredness,
      stress, time pressure, pain, intention, perceived behavioural control, priority,
      goal conflict and goal facilitation) were collected via a questionnaire for a
      period of between 3 and 7 months, which included time before and after the
      participant's retirement date. A personalised PA determinant was also identified
      by each participant and measured daily for the duration of the study. Dynamic
      regression models for discrete time binary data were used to analyse data for
      each individual participant. RESULTS: Two participants showed a statistically
      significant increase in the probability of engaging in PA bouts after retirement
      and two participants showed a significant time trend for a decrease and increase
      in PA bouts over time during the pre- to post-retirement period, respectively.
      There was no statistically significant change in PA after retirement for the
      remaining participants. Most of the daily questionnaire variables were
      significantly associated with PA for one or more participants but there were no
      consistent pattern of PA predictors across participants. For some participants,
      the relationship between questionnaire variables and PA changed from pre- to post
      retirement. CONCLUSIONS: The findings from this study demonstrate the impact of
      retirement on individual PA trajectories. Using n-of-1 methods can provide
      information about unique patterns and determinants of individual behaviour over
      time, which has been obscured in previous research. N-of-1 methods can be used as
      a tool to inform personalised PA interventions for individuals within the
      retirement transition.

PMID- 29221452
TI  - Evaluation of nutritional value, characteristics, functional properties of
      Cymodocea nodosa and its benefits on health diseases.
AB  - BACKGROUND: Nutritional fact study has prime importance to make the species
      edible and commercially viable to the food consumers. This is the first report
      that indicates the chemical characterization, functional, antioxidant and
      antihypertensive properties of Cymodocea nodosa to evaluate its nutritional
      status. METHODS: Physico-chemical determination was determined by colorimetric
      and spectroscopic analysis. The functional and texture properties were evaluated
      since a desirable texture should be retained. Bioactive substances were
      determined by liquid chromatography-high resolution electrospray ionization mass
      spectrometry HPLC-DAD-ESI/MS2 analysis. Health benefit of this plant was
      highlighting by the antioxidant and antihypertensive potentials. RESULTS: Results
      showed that the seagrass powder was characterized by a high content of fibers
      (56.4%), the fatty acids profile was dominated by the oleic acid, which
      represents about 62.0% of the total fatty acids and the functional properties
      proved important values of swelling capacity (6.71 +/- 0.2) and water holding
      capacity (12.26 +/- 0.25), that were comparable to those of some foodstuffs.
      Finally, the physico-chemical analysis shows the wealth in phenolic compounds,
      that could be explained by the high antioxidant and antihypertensive ability
      which was concentration dependent. CONCLUSION: The results from this study
      suggested that this marine plant could be utilized as a healthy food item for
      human consumption.

PMID- 29221453
TI  - The extra cost of comorbidity: multiple illnesses and the economic burden of non
      communicable diseases.
AB  - BACKGROUND: The literature offers competing estimates of disease costs, with each
      study having its own data and methods. In 2007, the Dutch Center for Public
      Health Forecasting of the National Institute for Public Health and the
      Environment provided guidelines that can be used to set up cost-of-illness (COI)
      studies, emphasising that most COI analyses have trouble accounting for
      comorbidity in their cost estimations. When a patient has more than one chronic
      condition, the conditions may interact such that the patient's healthcare costs
      are greater than the sum of the costs for the individual diseases. The main
      objective of this work was to estimate the costs of 10 non-communicable diseases
      when their co-occurrence is acknowledged and properly assessed. METHODS: The
      French Echantillon Generaliste de Beneficiaires (EGB) database was used to assign
      all healthcare expenses for a representative sample of the population covered by
      the National Health Insurance. COIs were estimated in a bottom-up approach,
      through regressions on individuals' healthcare expenditure. Two-way interactions
      between the 10 chronic disease variables were included in the expenditure model
      to account for possible effect modification in the presence of comorbidity(ies).
      RESULTS: The costs of the 10 selected chronic diseases were substantially higher
      for individuals with comorbidity, demonstrating the pattern of super-additive
      costs in cases of diseases interaction. For instance, the cost associated with
      diabetes for people without comorbidity was estimated at 1776 ?, whereas this was
      2634 ? for people with heart disease as a comorbidity. Overall, we detected 41
      cases of super-additivity over 45 possible comorbidities. When simulating a
      preventive action on diabetes, our results showed that significant monetary
      savings could be achieved not only for diabetes itself, but also for the chronic
      diseases frequently associated with diabetes. CONCLUSIONS: When comorbidity
      exists and where super-additivity is involved, a given preventive policy leads to
      greater monetary savings than the costs associated with the single diagnosis,
      meaning that the returns from the action are generally underestimated.

PMID- 29221451
TI  - Inequality in early childhood neurodevelopment in six poor rural counties of
      China: a decomposition analysis.
AB  - BACKGROUND: Previous studies about inequality in children's health focused more
      on physical health than the neurodevelopment. In this study, we aimed to evaluate
      the inequality in early childhood neurodevelopment in poor rural China and
      explore the contributions of socioeconomic factors to the inequality. METHOD:
      Information of 2120 children aged 0 to 35 months and their households in six poor
      rural counties of China was collected during July - September, 2013. Age and
      Stages Questionnaire-Chinese version, concentration index and decomposition
      analysis were used to assess the neurodevelopment of early childhood, measure its
      inequality and evaluate the contributions of socioeconomic factors to the
      inequality, respectively. RESULT: The prevalence of suspected developmental delay
      in children under 35 months of age in six poor rural counties of China was nearly
      40%, with the concentration index of -0.0877. Household economic status,
      caregivers' depressive symptoms, learning material and family support for
      learning were significantly associated with children's suspected developmental
      delay, and explained 34.1, 14.1, 8.9 and 7.0% of the inequality in early
      childhood neurodevelopment, respectively. CONCLUSION: The early childhood
      neurodevelopment in the surveyed area is poor and unfair. Factors including
      household economic status, caregivers' depressive symptoms, learning material and
      family support for learning are significantly associated with children's
      suspected developmental delay and early developmental inequality. The results
      highlight the urgent need of monitoring child neurodevelopment in poor rural
      areas. Interventions targeting the caregivers' depressive symptoms, providing
      learning material and developmental appropriate stimulating activities may help
      improve early childhood neurodevelopment and reduce its inequality.

PMID- 29221454
TI  - Must we remain blind to undergraduate medical ethics education in Africa? A cross
      sectional study of Nigerian medical students.
AB  - BACKGROUND: As the practice of medicine inevitably raises both ethical and legal
      issues, it had been recommended since 1999 that medical ethics and human rights
      be taught at every medical school. Most Nigerian medical schools still lack a
      formal undergraduate medical ethics curriculum. Medical education remains largely
      focused on traditional medical science components, leaving the medical students
      to develop medical ethical decision-making skills and moral attitudes passively
      within institutions noted for relatively strong paternalistic traditions. In
      conducting a needs assessment for developing a curriculum germane to the Nigerian
      society, and by extension most of Sub-Saharan Africa, this study determined the
      views of Nigerian medical students on medical ethics education, ethical issues
      related to the doctor-patient relationship and the ethical/professional dilemmas
      they are confronted with. METHODS: Using self-administered 63-item structured
      questionnaires, a cross-sectional survey of the final year medical students of
      the University of Nigeria was conducted in July 2015.Using the Statistical
      Package for the Social Sciences software (SPSS Version 17), frequency counts and
      percentages were generated. RESULTS: The sample included 100 males (71.4%) and 40
      females (28.6%), with the respective mean (SD) age being 24.6(5.61) and 21.8
      (6.38) years. Only 35.7% were satisfied with their medical ethics knowledge, and
      97.9% indicated that medical ethics should be taught formally. Only 8.6% had
      never witnessed a medical teacher act unethically. The dilemmas of poor
      communication between physicians and patients, and the provision of sub-standard
      care were reported highest for being encountered 'often'. A majority (60.7%)
      indicated that "a doctor should do his best always, irrespective of the patient's
      wishes". No significant difference in responses across gender was noted.
      CONCLUSION: There is a strong desire by the contemporary Nigerian medical student
      for medical ethics education. Their lack of exposure in medical ethics in an
      ethically challenging environment suggest a dire need for the development of an
      appropriate medical ethics curriculum for them and the provision of an ethically
      conducive learning environment.

PMID- 29221455
TI  - Mental health professionals' family-focused practice with families with dependent
      children: a survey study.
AB  - BACKGROUND: Many people with a mental illness are parents caring for dependent
      children. These children are at greater risk of developing their own mental
      health concerns compared to other children. Mental health services are opportune
      places for healthcare professionals to identify clients' parenting status and
      address the needs of their children. There is a knowledge gap regarding Thai
      mental health professionals' family-focused knowledge and practices when working
      with parents with mental illness and their children and families. METHODS: This
      cross -sectional survey study examined the attitudes, knowledge and practices of
      a sample (n = 349) of the Thai mental health professional workforce (nurses,
      social workers, psychologists, psychiatrists) using a translated version of the
      Family-Focused Mental Health Practice Questionnaire (FFMHPQ). RESULTS: The
      majority of clinicians reported no training in family (76.8%) or child-focused
      practice (79.7%). Compared to other professional groups, psychiatric nurses
      reported lower scores on almost all aspects of family-focused practice except
      supporting clients in their parenting role within the context of their mental
      illness. Social workers scored highest overall including having more workplace
      support for family-focused practice as well as a higher awareness of family
      focused policy and procedures than psychiatrists; social workers also scored
      higher than psychologists on providing support to families and parents. All
      mental health care professional groups reported a need for training and inter
      professional practice when working with families. CONCLUSIONS: The findings
      indicate an important opportunity for the prevention of intergenerational mental
      illness in whose parents have mental illness by strengthening the professional
      development of nurses and other health professionals in child and family-focused
      knowledge and practice.

PMID- 29221456
TI  - Effect of multimorbidity on quality of life in adult with cardiovascular disease:
      a cross-sectional study.
AB  - BACKGROUND: The aim of present study was to describe the effect of multimorbidity
      on Health-Related Quality of Life (HRQoL) in patients with coronary artery
      disease (CAD). METHODS: A cross-sectional study with a simple sampling method of
      296 patients undergoing coronary artery bypass surgery in a referral hospital of
      the northern part of Iran was conducted between April, 2015 and September, 2016.
      Multimorbidity was defined as the presence of at least two chronic diseases based
      on self-reporting and medical records. HRQoL was measured using the 36-item short
      form (SF-36) health status survey. We used analysis of variance (ANOVA) to assess
      the effect of multimorbidity on mental and physical component of HRQoL. RESULTS:
      Approximately, 69% of CAD patients had at least one other disease like diabetes
      or hypertension. Patients without multimorbidity compared with patients with
      multimorbidity were significantly older (p = 0.012) and more educated (p =
      0.002). Both physical and mental component score of HRQoL was better in patients
      without any morbidity (48.82 vs. 43.93 with 95%CI of mean difference: 3.37-6.42
      and 54.85 vs. 50.44 with 95% CI of mean difference: 1.68-7.15, respectively).
      Both physical and mental component score was significantly lower in female and
      lower educated patients (physical mean score 43.07 vs. 46.54 with P = .001 and
      42.53 vs. 46.82 with P < .001 and mental mean score 49.98 vs. 52.65 with P = .055
      and 49.80 vs. 52.75 with P = .022 for sex and education, respectively). Also, two
      way ANOVA showed that regards to morbidity, physical component score was grater
      in patients with lower education level than higher education level (P < .001).
      CONCLUSION: The findings of this study suggest that women, lower education level
      and overweight reported lower quality of life. HRQoL is affected by
      multimorbidity among CAD patients specially in less educated.

PMID- 29221457
TI  - Capillaria hepatica (Calodium hepaticum) infection in a horse: a case report.
AB  - BACKGROUND: Capillaria hepatica is a zoonotic parasite in humans and animals and
      has a worldwide distribution. However, infections in mammals apart from rodents,
      which are natural hosts of the parasite, have rarely been reported. This report
      describes the first known case of C. hepatica infection in a horse in Japan. CASE
      PRESENTATION: A 3-year-old filly without clinical signs was presented at a
      slaughterhouse in Japan. Gross examination revealed white to tan nodules 0.5 to
      1.5 cm in diameter in the parenchyma of the liver. Histologically, the nodules
      had mature fibrous capsules and consisted of multifocal to coalescing
      granulomatous inflammations with numerous nematode eggs. The eggs were barrel
      shaped with an opercular plug on each end and double-layered shells; these
      findings are consistent with the features of C. hepatica eggs. CONCLUSIONS: To
      our knowledge, this is the first case of C. hepatica infection in a horse in
      Japan. The pathological findings confirmed the presence of this pathogen in this
      part of the world, and they highlight the importance of this nematode in the
      differential diagnosis of hepatic granulomatous lesions in horses.

PMID- 29221458
TI  - A cohort examination to establish reporting of the remit and function of Trial
      Steering Committees in randomised controlled trials.
AB  - BACKGROUND: The DAMOCLES project established a widely used Data Monitoring
      Committee (DMC) Charter for randomised controlled trials (RCTs). Typically,
      within the UK, the DMC is advisory and recommends to another executive body; the
      Trial Steering Committee (TSC). Despite the executive role of the TSC, the
      CONSORT Statement does not explicitly require reporting of TSC activity, although
      is included as an example of good reporting. A lack of guidance on TSC reporting
      can impact transparency of trial oversight, ultimately leading to a
      misunderstanding regarding role and, subsequently, further variation in practice.
      This review aimed to establish reporting practice of TSC involvement in RCTs, and
      thus make recommendations for reporting. METHODS: A cohort examination
      identifying reporting practice was undertaken. The cohort comprised RCTs
      published in three leading medical journals (the British Medical Journal, The
      Lancet and the New England Journal of Medicine) within 6 months in 2012 and the
      full NIHR HTA Monograph series. Details of TSC constitution and impact were
      extracted from main publications and published supplements. RESULTS: Of 415
      publications, 264 were eligible. These were typical in terms of trial design.
      Variations in reporting between journals and monographs was notable. TSC presence
      was identified in approximately half of trials (n = 144), of which 109 worked
      alongside a DMC. No publications justified not convening a TSC. When reported,
      the role of the committee and examples of impact in design, conduct and analysis
      were summarised. CONCLUSIONS: We present the first review of reporting TSC
      activity in the published academic literature. An absence of reporting standards
      with regards to TSC constitution, activity and impact on trial conduct was
      identified which can influence transparency of reporting trial oversight.
      Consistent reporting is vital for the benefits and impact of the TSC role to be
      understood to support adoption of this oversight structure and reduce global
      variations in practice.

PMID- 29221459
TI  - Team-based learning (TBL) in the medical curriculum: better than PBL?
AB  - BACKGROUND: Internationally, medical schools have long used a variety of
      approaches to develop hybrid Problem based learning (PBL) curricula. However,
      Team-based learning (TBL), has gained recent popularity in medical education. TBL
      maintains the advantages of small group teaching and learning, but in contrast to
      Problem-based learning (PBL), does not require large numbers of tutors. In 2016,
      TBL was introduced to Year 1 of the Sydney Medical Program (SMP).This study
      sought to compare students' perceptions of using TBL in place of PBL. METHODS:
      Year 1 students (n = 169) completed three PBL and three TBL sessions during one
      of the following teaching blocks: Musculoskeletal (n = 56), Respiratory (n = 59)
      or Cardiovascular (n = 54). Student feedback following completion of each block
      of teaching was collected by questionnaire, using closed and open ended items.
      Data were analysed using descriptive statistics and thematic analysis. RESULTS:
      In total, 144/169 (85%) of participants completed a questionnaire regarding PBL,
      and 152/169 (90%) completed a similar questionnaire regarding TBL. The students
      found positive aspects of their TBL experience to include the smaller group size,
      the use of readiness assurance tests, immediate feedback from senior clinicians,
      and time efficiency. In PBL, students reported that variable expertise of tutors;
      limited direction; and large group size hindered their learning. CONCLUSIONS:
      Overwhelmingly, students preferred TBL over PBL, as the optimal teaching
      strategy. Students found the structure and format of the TBL sessions more
      conducive to learning, engagement and participation than PBL sessions. Although
      the use of TBL required an instructional approach, needing direction from the
      tutor, it remained student-centred, generating a range of positive outcomes.
      Study results provide confidence to change from PBL to TBL within Year 1 and Year
      2 of the SMP in 2017.

PMID- 29221460
TI  - GoldenPiCS: a Golden Gate-derived modular cloning system for applied synthetic
      biology in the yeast Pichia pastoris.
AB  - BACKGROUND: State-of-the-art strain engineering techniques for the host Pichia
      pastoris (syn. Komagataella spp.) include overexpression of homologous and
      heterologous genes, and deletion of host genes. For metabolic and cell
      engineering purposes the simultaneous overexpression of more than one gene would
      often be required. Very recently, Golden Gate based libraries were adapted to
      optimize single expression cassettes for recombinant proteins in P. pastoris.
      However, an efficient toolbox allowing the overexpression of multiple genes at
      once was not available for P. pastoris. METHODS: With the GoldenPiCS system, we
      provide a flexible modular system for advanced strain engineering in P. pastoris
      based on Golden Gate cloning. For this purpose, we established a wide variety of
      standardized genetic parts (20 promoters of different strength, 10 transcription
      terminators, 4 genome integration loci, 4 resistance marker cassettes). RESULTS:
      All genetic parts were characterized based on their expression strength measured
      by eGFP as reporter in up to four production-relevant conditions. The promoters,
      which are either constitutive or regulatable, cover a broad range of expression
      strengths in their active conditions (2-192% of the glyceraldehyde-3-phosphate
      dehydrogenase promoter P GAP ), while all transcription terminators and genome
      integration loci led to equally high expression strength. These modular genetic
      parts can be readily combined in versatile order, as exemplified for the
      simultaneous expression of Cas9 and one or more guide-RNA expression units.
      Importantly, for constructing multigene constructs (vectors with more than two
      expression units) it is not only essential to balance the expression of the
      individual genes, but also to avoid repetitive homologous sequences which were
      otherwise shown to trigger "loop-out" of vector DNA from the P. pastoris genome.
      CONCLUSIONS: GoldenPiCS, a modular Golden Gate-derived P. pastoris cloning
      system, is very flexible and efficient and can be used for strain engineering of
      P. pastoris to accomplish pathway expression, protein production or other
      applications where the integration of various DNA products is required. It allows
      for the assembly of up to eight expression units on one plasmid with the ability
      to use different characterized promoters and terminators for each expression
      unit. GoldenPiCS vectors are available at Addgene.

PMID- 29221461
TI  - Seeking a second medical opinion: composition, reasons and perceived outcomes in
      Israel.
AB  - BACKGROUND: Seeking a second-opinion (SO) is a common clinical practice that can
      optimize treatment and reduce unnecessary procedures and risks. We aim to
      characterize the composition of the population of SO seekers, their reasons for
      seeking a SO and choosing a specific physician, and their perceived outcomes
      following the SO. METHODS: A cross-sectional national telephone survey, using a
      representative sample of the general Israeli population (n = 848, response rate =
      62%). SO utilization was defined as seeking an additional clinical opinion from a
      specialist within the same specialty, for the same medical concern. We describe
      the characteristics of respondents who obtained SOs, their reasons for doing so
      and their perceived outcomes: (1) Satisfaction with the SO; (2) Experiencing
      health improvement after receiving a SO; (3) A difference in the diagnosis or
      treatment suggested in the first opinions and the second opinions; (4) Preference
      of the SO over the first one. RESULTS: Most of the respondents who sought a SO (n
      = 344) were above 60 years old, secular, living with a partner, perceived their
      income to be above average and their health status to be not so good. For the
      patients who utilized SOs, orthopedic surgeons were sought out more than any
      other medical professional.Reasons for seeking a SO included doubts about
      diagnosis or treatment (38%), search for a sub-specialty expert (19%) and
      dissatisfaction with communication (19%). SO seekers most frequently chose a
      specific specialist based on a recommendation from a friend or a relative (33%).
      About half of the SO seekers also searched for information on the internet. Most
      of the respondents who sought a SO mentioned that they were satisfied with it
      (84%), felt health improvement (77%), mentioned that there was a difference
      between the diagnosis or treatment between the first opinion and the SO (56%) and
      preferred the SO over the first one (91%). CONCLUSIONS: Clinical uncertainty or
      dissatisfaction with patient-physician communication were the main reasons for
      seeking a SO. Policy makers should be aware that many patients choose a physician
      for a SO based on recommendations made outside the medical system. We recommend
      creating mechanisms that help patients in the complicated process of seeking a
      SO, suggest specialists who are suitable for the specific medical problem of the
      patient, and provide tools to reconcile discrepant opinions.

PMID- 29221462
TI  - Ethical frameworks for obtaining informed consent in tumour profiling: an
      evidence-based case for Singapore.
AB  - BACKGROUND: Genomic profiling of malignant tumours has assisted clinicians in
      providing targeted therapies for many serious cancer-related illnesses. Although
      the characterisation of somatic mutations is the primary aim of tumour profiling
      for treatment, germline mutations may also be detected given the heterogenous
      origin of mutations observed in tumours. Guidance documents address the return of
      germline findings that have health implications for patients and their genetic
      relations. However, the implications of discovering a potential but unconfirmed
      germline finding from tumour profiling are yet to be fully explored. Moreover, as
      tumour profiling is increasingly applied in oncology, robust ethical frameworks
      are required to encourage large-scale data sharing and data aggregation linking
      molecular data to clinical outcomes, to further understand the role of genetics
      in oncogenesis and to develop improved cancer therapies. RESULTS: This paper
      reports on the results of empirical research that is broadly aimed at developing
      an ethical framework for obtaining informed consent to return results from tumour
      profiling tests and to share the biomolecular data sourced from tumour tissues of
      cancer patients. Specifically, qualitative data were gathered from 36 semi
      structured interviews with cancer patients and oncology clinicians at a cancer
      treatment centre in Singapore. The interview data indicated that patients had a
      limited comprehension of cancer genetics and implications of tumour testing.
      Furthermore, oncology clinicians stated that they lacked the time to provide in
      depth explanations of the tumour profile tests. However, it was accepted from
      both patients and oncologist that the return potential germline variants and the
      sharing of de-identified tumour profiling data nationally and internationally
      should be discussed and provided as an option during the consent process.
      CONCLUSIONS: Findings provide support for the return of tumour profiling results
      provided that they are accompanied with an adequate explanation from qualified
      personnel. They also support the use of broad consent regiments within an ethical
      framework that promotes trust and benefit sharing with stakeholders and provides
      accountability and transparency in the storage and sharing of biomolecular data
      for research.

PMID- 29221463
TI  - Correction to: Recessive VARS2 mutation underlies a novel syndrome with epilepsy,
      mental retardation, short stature, growth hormone deficiency, and hypogonadism.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that there is a nomenclature issue with this article. At the time of
      acceptance, the VARS2 mutation was considered equivalent to the VARS2 mutation.
      However, this has changed so that VARS now only refers to shorter mitochondrial
      sequence of valyl-tRNA synthesase containing 1093 amino acids. "Therefore, in the
      context of this article, every usage of "VARS2" should be replaced with "VARS"
      when referring to the causative variant".

PMID- 29221464
TI  - Molecular and functional characterization of ferredoxin NADP(H) oxidoreductase
      from Gracilaria chilensis and its complex with ferredoxin.
AB  - BACKGROUD: Ferredoxin NADP(H) oxidoreductases (EC 1.18.1.2) (FNR) are
      flavoenzymes present in photosynthetic organisms; they are relevant for the
      production of reduced donors to redox reactions, i.e. in photosynthesis, the
      reduction of NADP+ to NADPH using the electrons provided by Ferredoxin (Fd), a
      small FeS soluble protein acceptor of electrons from PSI in chloroplasts. In
      rhodophyta no information about this system has been reported, this work is a
      contribution to the molecular and functional characterization of FNR from
      Gracilaria chilensis, also providing a structural analysis of the complex FNR/Fd.
      METHODS: The biochemical and kinetic characterization of FNR was performed from
      the enzyme purified from phycobilisomes enriched fractions. The sequence of the
      gene that codifies for the enzyme, was obtained using primers designed by
      comparison with sequences of Synechocystis and EST from Gracilaria. 5'RACE was
      used to confirm the absence of a CpcD domain in FNRPBS of Gracilaria chilensis. A
      three dimensional model for FNR and Fd, was built by comparative modeling and a
      model for the complex FNR: Fd by docking. RESULTS: The kinetic analysis shows
      KMNADPH of 12.5 M and a k cat of 86 s-1, data consistent with the parameters
      determined for the enzyme purified from a soluble extract. The sequence for FNR
      was obtained and translated to a protein of 33646 Da. A FAD and a NADP+ binding
      domain were clearly identified by sequence analysis as well as a chloroplast
      signal sequence. Phycobilisome binding domain, present in some cyanobacteria was
      absent. Transcriptome analysis of Gch revealed the presence of two Fd; FdL and
      FdS , sharing the motif CX5CX2CX29X. The analysis indicated that the most
      probable partner for FNR is FdS. CONCLUSION: The interaction model produced, was
      consistent with functional properties reported for FNR in plants leaves, and
      opens the possibilities for research in other rhodophyta of commercial interest.

PMID- 29221466
TI  - Unusual pathological fracture of the clavicle revealing primary
      hyperparathyroidism: a case report.
AB  - BACKGROUND: Primary hyperparathyroidism revealed by a pathological fracture is
      very uncommon; in the majority of cases the discovery of lytic bone lesions on
      imaging examinations evokes in the clinician first a neoplastic etiology and a
      metabolic origin is often omitted. This case report adds to the existing
      literature as it describes an unusual presentation of primary
      hyperparathyroidism. CASE PRESENTATION: We report a case of a 50-year-old
      Moroccan man, without any known tumor, who presented a fracture of his left
      clavicle with multiple osteolytic lesions on computed tomography suggesting bone
      metastases. However, bone scintigraphy oriented the diagnosis to a metabolic
      pathology by showing a metabolic bone "super scan" with increased tracer uptake
      in the left clavicle; parathyroid scintigraphy was able to localize pathological
      right parathyroid tissue. CONCLUSIONS: Whenever multiple osteolytic lesions are
      found in a patient without any known tumor, metabolic bone diseases including
      hyperparathyroidism should be highly considered.

PMID- 29221465
TI  - Yale school of public health symposium on lifetime exposures and human health:
      the exposome; summary and future reflections.
AB  - The exposome is defined as "the totality of environmental exposures encountered
      from birth to death" and was developed to address the need for comprehensive
      environmental exposure assessment to better understand disease etiology. Due to
      the complexity of the exposome, significant efforts have been made to develop
      technologies for longitudinal, internal and external exposure monitoring, and
      bioinformatics to integrate and analyze datasets generated. Our objectives were
      to bring together leaders in the field of exposomics, at a recent Symposium on
      "Lifetime Exposures and Human Health: The Exposome," held at Yale School of
      Public Health. Our aim was to highlight the most recent technological
      advancements for measurement of the exposome, bioinformatics development, current
      limitations, and future needs in environmental health. In the discussions, an
      emphasis was placed on moving away from a one-chemical one-health outcome model
      toward a new paradigm of monitoring the totality of exposures that individuals
      may experience over their lifetime. This is critical to better understand the
      underlying biological impact on human health, particularly during windows of
      susceptibility. Recent advancements in metabolomics and bioinformatics are
      driving the field forward in biomonitoring and understanding the biological
      impact, and the technological and logistical challenges involved in the analyses
      were highlighted. In conclusion, further developments and support are needed for
      large-scale biomonitoring and management of big data, standardization for
      exposure and data analyses, bioinformatics tools for co-exposure or mixture
      analyses, and methods for data sharing.

PMID- 29221467
TI  - Urothelial cells may indicate underlying bacteriuria in pregnancy at term: a
      comparative study.
AB  - BACKGROUND: Urinary tract infection is common in pregnancy. Urine is sampled from
      by mid-stream collection (MSU). If epithelial cells are detected, contamination
      by vulvo-vagial skin and skin bacteria is assumed. Outside pregnancy, catheter
      specimen urine (CSU) is considered less susceptible to contamination. We compared
      MSU and CSU methods in term pregnancy to test these assumptions. METHODS: Healthy
      pregnant women at term gestation (n = 32, median gestation 38 + 6 weeks, IQR 37 +
      6-39 + 2) undergoing elective caesarean section provided a MSU and CSU for paired
      comparison that were each analysed for bacterial growth and bladder distress by
      fresh microscopy, sediment culture and immunofluorescent staining. Participants
      completed a detailed questionnaire on lower urinary tract symptoms. Epithelial
      cells found in urine were tested for urothelial origin by immunofluorescent
      staining of Uroplakin III (UP3), a urothelial cell surface glycoprotein.
      Urothelial cells with closely associated bacteria, or "clue cells", were also
      counted. Wilcoxons signed rank test was used for paired analysis. RESULTS: Women
      reported multiple lower urinary tract symptoms (median 3, IQR 0-8). MSU had
      higher white blood cell counts (median 67 vs 46, z = 2.75, p = 0.005) and
      epithelial cell counts (median 41 vs 22, z = 2.57, p = 0.009) on fresh
      microscopy. The proportion of UP3+ cells was not different (0.920 vs 0.935, z =
      0.08, p = 0.95), however MSU had a higher proportion of clue cells (0.978 vs
      0.772, z = 3.17, p = 0.001). MSU had more bacterial growth on sediment culture
      compared to CSU specimens (median 8088 total cfu/ml vs 0, z = 4.86, p = 0.001).
      Despite this, routine laboratory cultures reported a negative screening culture
      for 40.6% of MSU specimens. CONCLUSION: Our findings have implications for the
      correct interpretation of MSU findings in term pregnancy. We observed that MSU
      samples had greater bacterial growth and variety when compared to CSU samples.
      The majority of epithelial cells in both MSU and CSU samples were urothelial in
      origin, implying no difference in contamination. MSU samples had a higher
      proportion of clue cells to UP3+ cells, indicating a greater sensitivity to
      bacterial invasion. Urinary epithelial cells should not be disregarded as
      contamination, instead alerting us to underlying bacterial activity.

PMID- 29221469
TI  - Correction to: The role of melatonin in the onset and progression of type 3
      diabetes.
AB  - CORRECTION TO: MOLECULAR BRAIN (2017) 10:35 DOI: 10.1186/S13041-017-0315-X: In
      the original version of this article [1], published on 1 August 2017, Fig. 3
      contains a typo. In this Correction the incorrect and correct version of Fig. 3
      are shown. - Fig. 3 was originally published like this: - The correct version of
      Fig. 3 looks like this.

PMID- 29221468
TI  - Fever in pregnancy and the risk of congenital malformations: a cohort study.
AB  - BACKGROUND: In a variety of animal species, hyperthermia in pregnancy has been
      recognized as teratogenic. Hyperthermia interferes with protein synthesis via
      heat-shock proteins, which can entail membrane disruption, cell death, vascular
      disruption, and placental infarction. This can induce severe fetal malformations
      or death. Fever during pregnancy, especially during embryogenesis, has also been
      associated with congenital malformations in human offspring. The purpose of this
      large cohort study of clinically recognized pregnancies was to investigate
      whether fever during first trimester was associated with an increased risk of
      congenital malformations in the offspring. METHODS: The Danish National Birth
      Cohort is a population-based cohort of 100,418 pregnant women and their offspring
      recruited in 1996 to 2002. Information on fever during pregnancy was collected
      prospectively by means of two telephone interviews. The study population
      comprised the 77,344 pregnancies enrolled in the Danish National Birth Cohort
      where self-reported information on fever during first trimester of pregnancy was
      available. Pregnancy outcomes were identified through linkage with the National
      Patient Registry. Congenital malformations within the first three and a half
      years of life were categorized according to EUROCAT's classification criteria.
      Logistic regression models were used to estimate the associations between fever
      in first trimester and overall congenital malformations and congenital
      malformations by subgroups. RESULTS: Eight thousand three hundred twenty-one
      women reported fever during first trimester (10.8%) and 2876 infants were
      diagnosed with a congenital malformation (3.7%). Fever during first trimester did
      not affect the risk of overall fetal congenital malformation (OR 0.99, 95% CI
      0.88-1.12). The subgroup analyses indicated slightly higher risk of congenital
      anomalies in the eye, ear, face and neck (OR 1.29, 95% CI 0.78-2.12) and in the
      genitals (OR 1.17, 95% CI 0.79-1.12), whereas lower risk of malformations in the
      nervous system (OR 0.47, 95% CI 0.21-1.08), the respiratory system (OR 0.56, 95%
      CI 0.23-1.29) and in the urinary subgroup (OR 0.58, 95% CI 0.35-0.99) was
      suggested, the latter constituting the only statistically significant finding.
      CONCLUSIONS: Overall, this study did not show any association between maternal
      fever in pregnancy and risk of congenital anomalies.

PMID- 29221470
TI  - Potential diagnostic markers of olanzapine efficiency for acute psychosis: a
      focus on peripheral biogenic amines.
AB  - BACKGROUND: Biomarkers are now widely used in many fields of medicine, and the
      identification of biomarkers that predict antipsychotic efficacy and adverse
      reactions is a growing area of psychiatric research. Monoamine molecules of the
      peripheral bloodstream are possible prospective biomarkers based on a growing
      body of evidence indicating that they may reflect specific changes in
      neurotransmitters in the brain. The aim of this study was to detect peripheral
      biogenic amine indicators of patients with acute psychosis and to test the
      correlations between the biological measures studied and the psychopathological
      status of the patients. METHODS: This research included 60 patients with acute
      psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we
      measured biogenic amine indicators, including mRNA levels of dopamine receptor D4
      (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear
      cells (PBMCs) using quantitative real-time polymerase chain reaction and serum
      dopamine concentrations by enzyme linked immunosorbent assay (ELISA).
      Psychopathological status was evaluated using psychometric scales. The
      assessments were conducted prior to and after 14 and 28 days of treatment.
      RESULTS: The administration of haloperidol, but not olanzapine, up-regulated
      5HTR2A mRNA in a linear manner, albeit without statistical significance (p =
      0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless,
      a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a
      longitudinal trajectory, suggesting co-expression of the two genes. A significant
      positive correlation was observed between 5HTR2A mRNA levels and total Positive
      and Negative Syndrome Scale (PANSS) scores in both groups of patients before
      treatment. A significant correlation between baseline 5HTR2A mRNA levels and
      PANSS scores on days 14 and 28 of treatment remained for patients treated with
      olanzapine only. Moreover, a significant positive correlation was observed
      between blood serum dopamine levels and scores on extrapyramidal symptom scales
      in the olanzapine group. CONCLUSIONS: The DRD4 and 5HTR2A genes are co-expressed
      in PBMCs during antipsychotic administration. Despite a correlation between the
      studied biogenic amine indicators and the psychopathological status of patients,
      reliable biomarkers of treatment response could not be determined.

PMID- 29221471
TI  - In-home versus hospital preoperative balance and proprioceptive training in
      patients undergoing TKR; rationale, design, and method of a randomized controlled
      trial.
AB  - BACKGROUND: Severe knee osteoarthritis, as well as the surgical procedure of
      total knee replacement that aims to reduce its symptoms, cause great
      deterioration on the proprioceptive system. Taking this fact into account, and
      considering that balance abilities positively influence the capacity to perform
      basic functional tasks, this trial aims to find the short and mid-term effects of
      a preoperative balance and proprioceptive training when conducted by patients
      undergoing total knee replacement. Along with the effects, it is intended to
      determine whether in-home based training can be as effective as hospital
      training. The results will help to conclude whether the possible benefits may
      outweigh the health costs. METHODS: Seventy-five participants will take part. The
      trial will include in-home and supervised hospital experimental training compared
      to a non-active control group in order to estimate the actual effect of the
      proposal against the benefits due exclusively to the surgical procedure.
      Interventions last 4 weeks prior to surgery, and the follow-up will be at 2w, 6w,
      and 1y following the operation. The primary outcomes are in agreement with the
      goals: self-reported functionality in terms of KOOS and overall balance in terms
      of the Berg Balance Scale. The secondary outcomes will include the measurements
      of static and dynamic balance abilities, pain, function, and quality of life.
      DISCUSSION: It is expected for the results of this trial to provide relevant
      information in order to decide if a specific intervention is cost-effective to be
      implemented in clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier NCT03100890 . Registered in April 4, 2017.

PMID- 29221472
TI  - Odontoblast-like differentiation and mineral formation of pulpsphere derived
      cells on human root canal dentin in vitro.
AB  - BACKGROUND: The revitalization or regeneration of the dental pulp is a preferable
      goal in current endodontic research. In this study, human dental pulp cell (DPC)
      spheres were applied to human root canal samples to evaluate their potential
      adoption for physiological tissue-like regeneration of the dental root canal by
      odontoblastic differentiation as well as cell-induced mineral formation. METHODS:
      DPC were cultivated into three-dimensional cell spheres and seeded on human root
      canal specimens. The evaluation of sphere formation, tissue-like behavior and
      differentiation as well as mineral formation of the cells was carried out with
      the aid of optical light microscopy, immunohistochemical staining and scanning
      electron microscopy (SEM). RESULTS: Spheres and cells migrated out of the spheres
      showed an intense cell-cell- and cell-dentin-contact with the formation of extra
      cellular matrix. In addition, the ingrowth of cell processes into dentinal
      tubules and the interaction of cell processes with the tubule walls were detected
      by SEM-imaging. Immunohistochemical staining of the odontoblast specific matrix
      proteins, dentin matrix protein-1, and dentin sialoprotein revealed an
      odontoblast-like cell differentiation in contact with the dentin surface. This
      differentiation was confirmed by SEM-imaging of cells with an odontoblast
      specific phenotype and cell induced mineral formation. CONCLUSIONS: The results
      of the present study reveal the high potential of pulp cells organized in spheres
      for dental tissue engineering. The odontoblast-like differentiation and the cell
      induced mineral formation display the possibility of a complete or partial
      "dentinal filling" of the root canal and the opportunity to combine this method
      with other current strategies.

PMID- 29221473
TI  - Prevalence of somatic and urogenital symptoms as well as psychological health in
      women aged 45 to 55 attending primary health care: a cross-sectional study.
AB  - BACKGROUND: Women's physical and mental ill-health such as stress-related
      symptoms, depression, pain, hypertension and urogenital health shows a marked
      increase around the ages 45-55 years. These women are an important group for
      Primary Health Care (PHC) due to their prevalent symptoms and illnesses. The aim
      of this study was to estimate the prevalence of somatic, psychological and
      urogenital symptoms in women aged 45-55 attending PHC and evaluate factors
      associated with severe symptoms. METHODS: One hundred and thirty-one women were
      recruited from PHC in southwestern Sweden. Data were obtained from two self
      reported questionnaires, the Menopause Rating Scale (MRS) and the Montgomery
      Asberg Depression Rating Scale (MADRS). RESULTS: Exhaustion, depressive mood,
      muscle and joint problems, sleep and sexual problems were the most prevalent
      reported symptoms. Half of the women reported heart discomfort. Depression and
      increasing age were correlated to more severe symptoms. CONCLUSION: We recommend
      that cardiovascular risk factors, musculoskeletal symptoms, sexual problems,
      sleeping problems and mental health should be actively asked for when women aged
      45 to 55 attend PHC. We propose that preventive counselling of women in PHC
      before the age 45 should be evaluated in future studies.

PMID- 29221474
TI  - Increased expression of neuregulin 1 in the urothelium of rat bladder with
      partial bladder outlet obstruction.
AB  - BACKGROUND: This study determined whether changes in the expression of neuregulin
      (NRG) 1, erbB2 tyrosine kinase (ErbB2) and the M2 muscarinic receptor in the
      urothelium and detrusor muscle of the rat bladder were associated with partial
      bladder outlet obstruction (PBOO). METHODS: Male Sprague-Dawley rats (body weight
      250-300 g) were used and subdivided into control (n = 10) and PBOO groups (n =
      20). PBOO was induced for 21 days, and the expression of NRG1, ErbB2 and M2
      muscarinic receptor mRNA and protein was evaluated using reverse transcriptase
      polymerase chain reaction (RT-PCR) and western blotting, respectively. RESULTS:
      In the urothelium of rat bladder samples, protein expression and mRNA expression
      of NRG1, ErbB2 and M2 muscarinic receptor were significantly increased in the
      PBOO group compared to the control group (p < 0.05). Only mRNA expression levels
      of NRG1/ ErbB2 were higher in the detrusor muscle of the PBOO group compared to
      the control group (p < 0.05). CONCLUSIONS: Our study demonstrated remarkable
      changes in the expression of NRG1/ErbB2 receptor mRNA and protein in the
      urothelium and muscle layer. These results suggest that NRG1 overexpression plays
      some kind of role against the PBOO-induced upregulated muscarinic receptors in
      detrusor overactivity.

PMID- 29221475
TI  - A critical realist evaluation of a music therapy intervention in palliative care.
AB  - BACKGROUND: Music therapy is increasingly used as an adjunct therapy to support
      symptom management in palliative care. However, studies to date have paid little
      attention to the processes that lead to changes in patient outcomes. To fill this
      gap, we examined the processes and experiences involved in the introduction of
      music therapy as an adjunct complementary therapy to palliative care in a hospice
      setting in the United Kingdom (UK). METHODS: Using a realistic evaluation
      approach, we conducted a qualitative study using a variety of approaches. These
      consisted of open text answers from patients (n = 16) on how music therapy helped
      meet their needs within one hospice in Northern Ireland, UK. We also conducted
      three focus groups with a range of palliative care practitioners (seven
      physicians, seven nursing staff, two social workers and three allied health
      professionals) to help understand their perspectives on music therapy's impact on
      their work setting, and what influences its successful implementation. This was
      supplemented with an interview with the music therapist delivering the
      intervention. RESULTS: Music therapy contains multiple mechanisms that can
      provide physical, psychological, emotional, expressive, existential and social
      support. There is also evidence that the hospice context, animated by a holistic
      approach to healthcare, is an important facilitator of the effects of music
      therapy. Examination of patients' responses helped identify specific benefits for
      different types of patients. CONCLUSIONS: There is a synergy between the
      therapeutic aims of music therapy and those of palliative care, which appealed to
      a significant proportion of participants, who perceived it as effective.

PMID- 29221476
TI  - Lexical neutrality in environmental health research: Reflections on the term
      walkability.
AB  - Neighbourhood environments have important implications for human health. In this
      piece, we reflect on the environments and health literature and argue that
      precise use of language is critical for acknowledging the complex and
      multifaceted influence that neighbourhood environments may have on physical
      activity and physical activity-related outcomes. Specifically, we argue that the
      term "neighbourhood walkability", commonly used in the neighbourhoods and health
      literature, constrains recognition of the breadth of influence that neighbourhood
      environments might have on a variety of physical activity behaviours. The term
      draws attention to a single type of physical activity and implies that a
      universal association exists when in fact the literature is quite mixed. To
      maintain neutrality in this area of research, we suggest that researchers adopt
      the term "neighbourhood physical activity environments" for collective measures
      of neighbourhood attributes that they wish to study in relation to physical
      activity behaviours or physical activity-related health outcomes.

PMID- 29221477
TI  - Trajectories and characteristics of functional impairment before and after
      suicide attempt in young adults - a nationwide register-based cohort study.
AB  - BACKGROUND: Despite high rates of youth suicide attempt, little is known about
      patterns of functional impairment in terms of sickness absence and disability
      pension (SA/DP) before and after an attempt. The aim was to identify SA/DP
      trajectories among young adults with or without suicide attempt and to describe
      associations of socio-demographic and clinical factors with such trajectories.
      METHODS: This is a population-based cohort study of 5385 individuals aged 25-40
      years with a first suicide attempt during 2007-2009. One control for each case
      without suicide attempt was matched by socio-demographic factors. Trajectories of
      annual SA/DP months over an eight-year period were analysed by group-based
      trajectory modelling. Associations between socio-demographic and clinical factors
      with trajectory groups were estimated by chi2-test and multinomial logistic
      regression. RESULTS: Two groups of suicide attempters had low SA/DP levels over
      time (62%). One group had constantly high SA/DP levels (16%). The remaining two
      groups had increased SA/DP initially, which then decreased at different time
      points. Socio-demographic and clinical factors were associated with different
      trajectories (R2 = 0.44). Suicide attempters with low levels of SA/DP were likely
      to be unemployed whereas a larger proportion of those with high levels of SA/DP
      had psychiatric health care before the suicide attempt, particularly due to
      schizophrenia and non-affective psychoses or personality disorders. CONCLUSIONS:
      Young suicide attempters even with no/low levels of SA/DP were likely to be
      marginalised at the labour market. Schizophrenia/non-affective psychoses and
      personality disorders were important clinical factors for differentiating the
      levels of SA/DP among young suicide attempters.

PMID- 29221478
TI  - Evaluation of antioxidant, anti-inflammatory, analgesic and antipyretic
      activities of the stem bark of Sapindus mukorossi.
AB  - BACKGROUND: Saponins are the main constituents of genus Sapindus and have the
      therapeutic potential for inflammatory disorders. In this study the antioxidant,
      anti-inflammatory, analgesic and antipyretic potential of the stem bark of soap
      nut (Sapindus mukorossi) methanol extract and its derived fractions has been
      investigated. METHODS: Powder of stem bark of the S. mukorossi was extracted with
      methanol (SMM) and fractionated in order of n-hexane (SMH), chloroform (SMC),
      ethyl acetate (SME), n-butanol (SMB) and the remaining as aqueous fraction (SMA).
      Quantitative estimation for the total phenolic and total flavonoid content was
      carried out in all the extract/fractions. Further, various in vitro antioxidant
      assays were also performed. Anti-inflammatory (Carrageenan induced paw edema),
      analgesic (hot plate latency test) and antipyretic (rectal temperature) were
      determined in Sprague-Dawley rat. RESULTS: Quantitative estimation of total
      phenolic contents in extract/fractions varied between 252.3 +/- 2.41 mg of GAE/g 
      594.16 +/- 4.3 mg of GAE/g while the total flavonoids estimated were from 11.02
      +/- 1.3 mg of RUE/g to 96.9 +/- 3.2 mg of RUE/g. Standard antioxidant assays such
      as scavenging of DPPH, hydroxyl radical, nitric oxide, phosphomolybdenum assay,
      reducing power, inhibition of beta-carotene bleaching, iron chelation activity
      and inhibition of heat induced protein denaturation indicated the antioxidant
      potential of the extract/fractions. Carrageenan induced paw edema of rat was
      effectively inhibited by SMA at 300 mg/kg administration to rat (84.19 +/- 1.48%)
      after 3 h and analgesia (latency time) in hot plate test (55.78 +/- 1.22%) after
      120 min. SMA at 300 mg/kg distinctly decreased the rectal temperature in brewer's
      yeast (Saccharomyces cerevisiae) induced pyrexia in rat. CONCLUSION: The resulted
      obtained in this study suggested the therapeutic importance of stem bark of S.
      mukorossi in inflammatory related disorders.

PMID- 29221479
TI  - In-screw polymethylmethacrylate-augmented sacroiliac screw for the treatment of
      fragility fractures of the pelvis: a prospective, observational study with 1-year
      follow-up.
AB  - BACKGROUND: The incidence of pelvic ring fractures in the elderly significantly
      increased. Because of persistent pain and immobilization associated with this
      injury, surgical treatment is recommended. To minimise comorbidities and surgical
      risk, percutaneous techniques are becoming more relevant. In-screw cement
      augmentation of sacroiliac screw fixation is a promising procedure; however,
      clinical follow-up data remain scarce. This study investigated the safety and
      possible complications of the procedure along with a 1-year follow-up. METHODS:
      Thirty-four patients (treated with 43 screws) were prospectively included. Data
      on patients' age and sex, the mechanism of accident, fracture pattern, duration
      of hospital stay, surgery and adverse events were recorded. Data were obtained
      postoperatively on the reduction of pain and complications, such as infection,
      cement leakage and neurological deficits, and at 1-year follow-up on pain,
      quality of life according to the 12-Item Short Form Survey and mobility. Implant
      failure was defined as retraction or dislocation of screws and was also
      documented. RESULTS: Screw-related complications occurred with 2 of 43 screws.
      None of these complications were related to cement augmentation. In-hospital
      adverse events occurred in 6 of 34 patients. Postoperative pain, measured by the
      visual analogue scale, was significantly reduced from 6.7 +/- 1.4 preoperatively
      to 2.7 +/- 1.0 postoperatively (p < 0.001). Although patients complained of pain
      at the 1-year follow-up, they reported a significant decline compared with pain
      at admission (3.4 +/- 2.3; p < 0.001). Results on the quality of life were
      comparable with those for the age- and gender matched German population. All
      patients were mobile, and no implant failure was detected. CONCLUSIONS: The
      results indicate that in-screw augmented sacroiliac screw fixation for fragility
      fractures of the pelvis is a safe technique. Pain was significantly reduced
      immediately after surgery compared to the preoperative state. Furthermore,
      significant pain reduction after one year compared to the preoperative state and
      quality of life was comparable to the age- and gender- matched German population.
      Thus, we recommend in-screw augmentation for screw fixation for sacral fragility
      fractures of the pelvis following failed conservative treatment.

PMID- 29221480
TI  - Prevalence and etiologies of pulmonary hypertension in Africa: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Despite the recent increasing worldwide attention towards pulmonary
      hypertension (PH), its epidemiology remains poorly described in Africa.
      Accordingly, we performed a systematic review and meta-analysis of PH prevalence,
      incidence and etiologies in Africa. METHODS: We searched PubMed, EMBASE, African
      Journals Online, and Africa Index Medicus. Published observational studies until
      September 20, 2017, including adult participants residing in Africa were
      considered. Two review authors independently selected studies, assessed included
      studies for methodological quality, and extracted data. A random-effects model
      was used for meta-analysis. Heterogeneity was evaluated by the chi 2 test on
      Cochrane's Q statistic which is quantified by I2 values. Using Newcastle-Ottawa
      Scale, we considered a score of 0-4, 5-7, and 8-10 as indicative of high,
      moderate, and low risk of bias in included studies, respectively. RESULTS: Of
      1611 entries, 25 studies were retained. Twelve (48%), seven (28%), and six (24%)
      papers had respectively a low, moderate and high risk of bias. The prevalence of
      PH widely varied across different populations: 9.8% (95% confidence interval: 3.2
      19.3; I2 = 99.4%; 6 studies) in 11,163 people presenting with cardiac complaints;
      10.6% (4.3-19.1; I2 = 90.3%; 4 studies) in 937 HIV-infected people; 32.9% (17.6
      50.4; I2 = 97.2%; 3 studies) in 2077 patients with heart failure; 23.2% (15.2
      32.2; I2 = 59.4%; 3 studies) in 248 patients on hemodialysis; 12.9% (11.8-14.0;
      I2 = 79.7%; 2 studies) in 3750 patients with rheumatic heart disease; 36.9% (29.7
      44.3; I2 = 79.7; 2 studies) in 79 patients with sickle cell disease; 62.7% (49.0
      74.7; 1 study) in 51 patients with chronic obstructive pulmonary disease; 25.4%
      (16.3-37.3; 1 study) in 63 patients with systemic lupus erythematous; 68.7% (62.8
      74.1; 1 study) in 259 patients with cardiac surgery; and 7.4% (4.6-11.9; 1 study)
      in 202 patients with systemic sclerosis. No study reported PH incidence. From one
      international study (n = 209), PH etiologies were: left heart disease (68.9%),
      pulmonary arterial hypertension (15.8%), lung disease and/or hypoxia (12.0%),
      chronic thromboembolic PH (1.9%) and unclear/multifactorial PH (15.8%).
      CONCLUSION: The prevalence of PH is relatively high in some populations in
      Africa, perhaps mainly driven by left heart diseases, highlighting the need for
      context-specific interventions.

PMID- 29221481
TI  - Association of body mass index with knee cartilage damage in an asymptomatic
      population-based study.
AB  - BACKGROUND: Cartilage changes are an important early finding of osteoarthritis
      (OA), which can exist even before symptoms. Our objective was to determine the
      prevalence of knee cartilage damage on magnetic resonance imaging (MRI) in an
      asymptomatic population-based cross-sectional study and to evaluate the
      association of body mass index (BMI) with cartilage damage. METHODS: Subjects,
      aged 40-79 years, without knee pain (n = 73) were recruited as a random
      population sample and assessed for BMI (kg/m2), including current BMI (measured),
      past BMI at age 25 (self-reported) and change in BMI. Knee cartilage was scored
      semi-quantitatively (grades 0-4) on MRI. In primary analysis, cartilage damage
      was defined as >=2 (at least moderate) and in a secondary analysis as >=3
      (severe). We also conducted a sensitivity analysis by dichotomizing current BMI
      as <25 vs. >=25. Logistic regression was used to evaluate the association of each
      BMI variable with prevalent MRI-detected cartilage damage, adjusted for age and
      sex. RESULTS: Of 73 subjects, knee cartilage damage >=2 and >=3 was present in
      65.4% and 28.7%, respectively. The median current BMI was 26.1, median past BMI
      21.6, and median change in BMI was a gain of 2.8. For cartilage damage >=2,
      current BMI had a non-statistically significant OR of 1.65 per 5 units (95% CI
      0.93-2.92). For cartilage damage >=3, current BMI showed a trend towards
      statistical significance with an OR of 1.70 per 5 units (95% CI 0.99-2.92). Past
      BMI and change in BMI were not significantly associated with cartilage damage.
      Current BMI >= 25 was statistically significantly associated with cartilage
      damage >=2 (OR 3.04 (95% CI 1.10-8.42)), but not for >=3 (OR 2.63 (95% CI 0.86
      8.03)). CONCLUSIONS: MRI-detected knee cartilage damage was highly prevalent in
      this asymptomatic population-based cohort. We report a trend towards significance
      of BMI with cartilage damage severity. Subjects with abnormal current BMI (>=25)
      had a 3-fold increased odds of cartilage damage >=2, compared to those with
      normal BMI. This study lends support towards the role of obesity in the
      pathogenesis of knee cartilage damage at an asymptomatic stage of disease.

PMID- 29221482
TI  - Rejection, acceptance and the spectrum between: understanding male attitudes and
      experiences towards conflict-related sexual violence in eastern Democratic
      Republic of Congo.
AB  - BACKGROUND: Female survivors of sexual violence in conflict experience not only
      physical and psychological sequelae from the event itself, but often many
      negative social outcomes, such as rejection and ostracisation from their families
      and community. Male relatives - whether husbands, fathers, brothers - play a key
      role in determining how the family and community respond to a survivor of sexual
      violence. Understanding these perspectives could help improve services for
      survivors of sexual violence, as well as their families and communities. METHODS:
      This study draws on qualitative data gathered from focus groups of 68 men in the
      eastern region of Democratic Republic of Congo. Men were asked about their
      experiences as relatives of women who had experienced sexual violence. RESULTS:
      Two dominant themes arose throughout the focus groups: factors driving rejection
      and pathways to acceptance. Factors driving rejection included: fear of sexually
      transmitted infections, social stigma directed toward the husbands themselves,
      and an understanding of marriage and fidelity that is incompatible with rape. Men
      also touched on their own trauma, including struggling with witnessing a rape
      that took place in public, or caring for a survivor with a child from rape. They
      noted that the economic burden of medical treatment for survivors was a salient
      factor in the decision to reject. Pathways to acceptance included factors such as
      the love of their spouse or relative, survivors' potential to give continued
      financial contribution to the family, the need to keep the family together to
      care for children in the home, and pressure from people of importance in the
      community. CONCLUSION: This study provides unique insight into how male relatives
      respond to close family members who have experienced sexual violence. This is
      particularly critical since the reaction of a male relative after rape can be the
      most pivotal factor in promoting or impeding recovery for a survivor. These
      results emphasise the importance of services that focus not only on the survivor
      of violence herself, but also on key family members that can ideally help support
      her recovery.

PMID- 29221483
TI  - The role of sleepiness on arterial stiffness improvement after CPAP therapy in
      males with obstructive sleep apnea: a prospective cohort study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased
      cardiovascular risk. This study aim to assess differences in changes in arterial
      stiffness of two groups of patients, defined as having daytime sleepiness or not,
      after continuous positive airway pressure (CPAP) treatment. METHODS: A selected
      cohort of consecutive male patients, under 65 years old, with moderate to severe
      OSA and without great number of comorbidities was studied. The diagnosis was
      confirmed by home respiratory poligraphy. Sleepiness was considered with an
      Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring
      and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed,
      before and after four months under CPAP. Compliant patients, sleepy and non
      sleepy, were compared using linear mixed effects regression models. A further
      stratified analysis was performed with non-sleepy patients. RESULTS: Thirty-four
      patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4%
      with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In
      univariable analysis, cf-PWV was strongly related to systolic BP parameters and
      age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p =
      0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA,
      with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study
      parameters were not associated with cf-PWV values. On multivariable regression, a
      significant interaction between time (CPAP) and sleepiness (p = 0.033) was found.
      There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086),
      but the effects of treatment differed significantly between groups, with no
      changes in non-sleepy patients, while in sleepy patients a significant decrease
      was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP
      therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL
      cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV
      changes. CONCLUSIONS: Patients with daytime sleepiness had a more severe OSA and
      presented a greater arterial stiffness improvement after CPAP therapy,
      independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP
      therapy was mainly associated to CV risk factors, and less to sleep study
      parameters. TRIAL REGISTRATION: Clinicaltrials.gov NCT02273089 23.10.2014
      retrospectively registered.

PMID- 29221484
TI  - The impacts of baseline ventilator parameters on hospital mortality in acute
      respiratory distress syndrome treated with venovenous extracorporeal membrane
      oxygenation: a retrospective cohort study.
AB  - BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a
      valuable life support in acute respiratory distress syndrome (ARDS) in adult
      patients. However, the success of VV-ECMO is known to be influenced by the
      baseline settings of mechanical ventilation (MV) before its institution. This
      study was aimed at identifying the baseline ventilator parameters which were
      independently associated with hospital mortality in non-trauma patients receiving
      VV-ECMO for severe ARDS. METHODS: This retrospective study included 106 non
      trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single
      medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia
      (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory
      pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and
      FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO
      were collected for analysis of hospital mortality. RESULTS: The causes of ARDS
      were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration
      pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO
      institution was 3 days and the overall hospital mortality was 53% (n = 56). The
      medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn)
      at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O,
      respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2
      ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O,
      respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and
      PCdyn were significantly correlated with the duration of MV before ECMO
      institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079-1.565, p <
      0.001) was found to be the only baseline ventilator parameter that independently
      affected the hospital mortality in these ECMO-treated patients. CONCLUSION: Since
      the duration of MV before ECMO institution was strongly correlated to the outcome
      of adult respiratory ECMO, medical centers are suggested to find a suitable
      prognosticating tool to determine the starting point of respiratory ECMO among
      their candidates with different duration of MV. TRIAL REGISTRATION: This study
      reported a health care intervention on human participants and was retrospectively
      registered. The Chang Gung Medical Foundation Institutional Review Board approved
      the study (no. 201601483B0 ) on November 23, 2016. All of the data were extracted
      from December 1, 2016, to January 31, 2017.

PMID- 29221485
TI  - Exploring the characteristics of patients with mesothelioma who chose active
      symptom control over chemotherapy as first-line treatment: a prospective,
      observational, single centre study.
AB  - BACKGROUND: Mesothelioma is an aggressive thoracic tumour with a poor prognosis.
      The only treatment that extends survival is chemotherapy. However, in the UK, up
      to 50% of patients who are suitable for chemotherapy choose not to receive it,
      opting for active symptom control instead. The aim of this prospective, single
      centre observational study was to describe the characteristics of patients who
      chose active symptom control over chemotherapy and explore their reasons for
      doing so. METHODS: Two hundred consecutive patients with mesothelioma from one UK
      centre were included. Eligibility for chemotherapy and choice of first-line
      treatment were recorded prospectively. Patient characteristics and outcomes were
      compared using descriptive statistics, regression analysis and survival analysis.
      Reasons for choosing active symptom control over chemotherapy were extracted,
      retrospectively. RESULTS: People who chose active symptom control were older,
      more likely to be female and had worse performance statuses than patients who
      received front-line chemotherapy. Concern over side effects, the modest survival
      benefit and previous adverse experiences with chemotherapy were reported as
      reasons for the decision. Median survival was 13.9 months in the chemotherapy
      group compared with 6.7 months in the active symptom control group. CONCLUSIONS:
      This is the first study to describe the characteristics of patients with
      mesothelioma who chose active symptom control over chemotherapy, in the front
      line setting. Important differences were seen between this group and patients who
      received chemotherapy, although confounding is likely to have affected some
      outcomes. Future research could use qualitative methods to explore patients'
      reasons for choosing active symptom control, and to further elucidate the
      decision-making process.

PMID- 29221486
TI  - A screening system to identify transcription factors that induce binding site
      directed DNA demethylation.
AB  - BACKGROUND: DNA methylation is a fundamental epigenetic modification that is
      involved in many biological systems such as differentiation and disease. We and
      others recently showed that some transcription factors (TFs) are involved in the
      site-specific determination of DNA demethylation in a binding site-directed
      manner, although the reports of such TFs are limited. RESULTS: Here, we develop a
      screening system to identify TFs that induce binding site-directed DNA
      methylation changes. The system involves the ectopic expression of target TFs in
      model cells followed by DNA methylome analysis and overrepresentation analysis of
      the corresponding TF binding motif at differentially methylated regions. It
      successfully identified binding site-directed demethylation of SPI1, which is
      known to promote DNA demethylation in a binding site-directed manner. We extended
      our screening system to 15 master TFs involved in cellular differentiation and
      identified eight novel binding site-directed DNA demethylation-inducing TFs
      (RUNX3, GATA2, CEBPB, MAFB, NR4A2, MYOD1, CEBPA, and TBX5). Gene ontology and
      tissue enrichment analysis revealed that these TFs demethylate genomic regions
      associated with corresponding biological roles. We also describe the
      characteristics of binding site-directed DNA demethylation induced by these TFs,
      including the targeting of highly methylated CpGs, local DNA demethylation, and
      the overlap of demethylated regions between TFs of the same family. CONCLUSIONS:
      Our results show the usefulness of the developed screening system for the
      identification of TFs that induce DNA demethylation in a site-directed manner.

PMID- 29221487
TI  - Clinical laboratory verification of thyroglobulin concentrations in the presence
      of autoantibodies to thyroglobulin: comparison of EIA, radioimmunoassay and LC
      MS/MS measurements in an Urban Hospital.
AB  - OBJECTIVE: Thyroglobulin (Tg) measurements assess recurrence in post
      thyroidectomy thyroid cancer patients. Tg measurements by enzyme immunoassays
      (EIA) can be falsely elevated by interference from Tg autoantibodies (TgAb).
      Radioimmunoassay (RIA) is less susceptible to TgAb interference and has been the
      standard-of-care test for TgAb positive patients. Recently developed liquid
      chromatography tandem mass spectrometry (LC-MS/MS) methods may eliminate TgAb
      interference. We assessed the performance of Tg measurements by EIA, RIA and LC
      MS/MS to evaluate TgAb interference differences. RESULTS: We measured TgAb and Tg
      in 50 plasma samples from 40 patients in whom Tg measurement was part of their
      routine follow-up and 10 healthy volunteers. Discrepancy between EIA and both LC
      MS/MS and RIA was observed at low Tg concentrations (<= 7.55 ng/mL) in TgAb
      positive specimens (LC-MS/MS = 1.9 * EIA - 0.03, r = 0.68). RIA and LC-MS/MS Tg
      measurements in TgAb positive specimens with low Tg concentrations had improved
      correlation but demonstrated bias (LC MS/MS = 0.6 * RIA - 1.4, r = 0.90).
      Disagreement between methods may be attributed to LC-MS/MS reported Tg
      concentrations as undetectable compared to RIA. It seems likely that most
      discrepant cases are falsely elevated in RIA due to TgAb interference, however,
      some cases appear below the detection limit of LC-MS/MS; implementation of LC
      MS/MS by clinicians will require lower detection limits.

PMID- 29221488
TI  - Divergent susceptibilities to AAV-SaCas9-gRNA vector-mediated genome-editing in a
      single-cell-derived cell population.
AB  - OBJECTIVE: Recombinant adeno-associated virus (AAV)-based vectors are
      characterized by their robust and safe transgene delivery. The CRISPR/Cas9 and
      guide RNA (gRNA) system present a promising genome-editing platform, and a recent
      development of a shorter Cas9 enzyme from Staphylococcus aureus (SaCas9) allows
      generation of high titer single AAV vectors which carry both saCas9- and gRNA
      expression cassettes. Here, we used two AAV-SaCas9 vectors with distinct GFP
      targeted gRNA sequences and determined the impact of AAV-SaCas9-gRNA vector
      treatment in a single cell clone carrying a GFP-expression cassette. RESULTS: Our
      results showed comparable GFP knockout efficiencies (40-50%) upon a single low
      dose infection. Three consecutive transductions of 25-fold higher doses of
      vectors showed 80% GFP knockout efficiency. To analyze the "AAV-SaCas9-resistant
      cell population", we sorted the residual GFP-positive cells and assessed their
      permissiveness to super-infection with two AAV-Cas9-GFP vectors. We found the
      sorted cells were significantly more resistant to the GFP knockout mediated by
      the same AAV vector, but not by the other GFP-targeted AAV vector. Our data
      therefore demonstrate highly efficient genome-editing by the AAV-SaCas9-gRNA
      vector system. Differential susceptibilities of single cell-derived cells to the
      AAV-SaCas9-gRNA-mediated genome editing may represent a formidable barrier to
      achieve 100% genome editing efficiency by this vector system.

PMID- 29221489
TI  - Characteristics of the use of cold combination products among older ambulatory
      patients at the National Hospital Organization Tochigi Medical Center in Japan: a
      retrospective single-center observational study.
AB  - OBJECTIVE: This study aimed to determine the frequency and characteristics of
      prescriptions of cold combination products among older ambulatory patients. A
      retrospective observational study was conducted using electronic medical records.
      All patients aged 65 years or older who continued visiting internal medicine
      physicians for at least 1 year were included. The primary outcome was the
      prescription of cold combination products by any physicians in National Hospital
      Organization Tochigi Medical Center during a 1-year follow-up. RESULTS: Seven
      hundred fifty-six patients were included. The mean age was 75.4 years, 392
      (51.9%) were men, the mean Charlson Comorbidity Index was 1.8, and the mean
      number of medications was 4.9. The proportion of patients who were prescribed
      cold combination products during the 1-year follow-up was 6.1% (95% confidence
      interval 4.4-7.8%). The prescription of cold combination products was not
      significantly associated with age (p = 0.11) or Charlson Comorbidity Index (p =
      0.93) but was associated with an increasing number of medications (p < 0.001). A
      substantial proportion of older ambulatory patients were exposed to cold
      combination products during a 1-year follow-up.

PMID- 29221490
TI  - The first detected airline introductions of yellow fever mosquitoes (Aedes
      aegypti) to Europe, at Schiphol International airport, the Netherlands.
AB  - BACKGROUND: Air-borne introduction of exotic mosquitoes to Schiphol airport in
      the Netherlands has been considered plausible based upon findings of mosquitoes
      in aircraft cabins during 2008, 2010 and 2011. Beginning in 2013, surveillance
      efforts at Schiphol had focused on promptly detecting accidental introductions at
      the airport facilities in order to quickly react and avoid temporary
      proliferation or establishment of mosquito populations, identify the origin of
      the introductions, and avoid potential transmission of vector-borne diseases.
      METHODS: BG-Mosquitaire mosquito traps were set at the most likely locations for
      arrival of the invasive Aedes mosquitoes as part of the mosquito monitoring
      program at Schiphol airport. Samples were collected bi-weekly. Upon detection of
      exotic specimens, information about the origin of the flights arriving to the
      particular location at the airport where specimens were captured was requested
      from airport authorities. The GIS tool Intersect was then used to identify
      airports of origin common to positive trapping locations during the specific
      trapping period. Captured Aedes aegypti mosquitoes were subsequently genotyped at
      12 highly polymorphic microsatellite markers and compared to a reference database
      of 79 populations around the world to further narrow down their location of
      origin. RESULTS: In 2016, six adult yellow fever mosquitoes were captured indoors
      and outdoors at the airport of Schiphol in the Netherlands confirming, for the
      first time, air-borne transport of this mosquito vector species into Europe.
      Mosquitoes were captured during three time periods: June, September and October.
      Containers carried by aircrafts are considered the most likely pathway for this
      introduction. GIS analysis and genetic assignment tests on these mosquitoes point
      to North America or the Middle East as possible origins, but the small sample
      size prevents us from reliably identifying the geographic origin of this
      introduction. CONCLUSIONS: The arrival of Ae. aegypti mosquitoes to Schiphol
      airport from flights arriving from overseas, demonstrates the potential risk of
      international flights to public health as carriers of arthropod vectors of
      disease. The results strongly suggest that disinsection of containers and their
      storage compartments inside the aircrafts could contribute to preventing future
      introductions of mosquito vectors. Invasive mosquito species introduced by
      aircrafts from overseas could become seasonally established during the warmer
      months in Europe, or permanently in certain climatically suitable areas for the
      species, with major consequences for human health.

PMID- 29221492
TI  - Elevated serum beta2-microglobulin in individuals coinfected with hepatitis B and
      hepatitis D virus in a rural settings in Southwest Nigeria.
AB  - OBJECTIVE: Coinfection of hepatitis B virus (HBV) with hepatitis D virus (HDV)
      has being reported to increase severity of progression to hepatocellular
      carcinoma (HCC) and liver cirrhosis (LC). Beta microglobulin (2betaM) which is
      present on the surfaces of blood cells in acceptable levels is a tumor marker
      which may become elevated in disease conditions. This study hence observed the
      prevalence of HBV and HDV coinfection in a rural population and their 2betaM
      concentration. RESULTS: Of the 368 samples, 66 (17.9%) were positive to hepatitis
      B surface antigen (HBsAg) and 33 (50%) were coinfected with HDV, 8 (2.1%) were
      monoinfected with HDV. 2betaM concentration increased beyond the normal level in
      individuals coinfected with HBV and HDV as compared with the monoinfected
      individuals. Coinfection resulted in the increased concentration of 2betaM in HBV
      and HDV coinfection and the likelihood of progression to HCC and LC may not be
      ruled out. Monoinfection with HDV also had high 2betaM concentration but this is
      due to having being infected with a non-detected HBV or chronic infection in
      which HBV is clearing.

PMID- 29221491
TI  - A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.
AB  - BACKGROUND: Gantenerumab is a fully human monoclonal antibody that binds
      aggregated amyloid-beta (Abeta) and removes Abeta plaques by Fc receptor-mediated
      phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of
      gantenerumab in prodromal Alzheimer's disease (AD). METHODS: In this randomized,
      double-blind, placebo-controlled phase III study, we investigated gantenerumab
      over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or
      placebo every 4 weeks by subcutaneous injection. The primary endpoint was the
      change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes (CDR
      SB) score. We evaluated treatment effects on cerebrospinal fluid biomarkers (all
      patients) and amyloid positron emission tomography (substudy). A futility
      analysis was performed once 50% of patients completed 2 years of treatment.
      Safety was assessed in patients who received at least one dose. RESULTS: Of the
      3089 patients screened, 797 were randomized. The study was halted early for
      futility; dosing was discontinued; and the study was unblinded. No differences
      between groups in the primary (least squares mean [95% CI] CDR-SB change from
      baseline 1.60 [1.28, 1.91], 1.69 [1.37, 2.01], and 1.73 [1.42, 2.04] for placebo,
      gantenerumab 105 mg, and gantenerumab 225 mg, respectively) or secondary clinical
      endpoints were observed. The incidence of generally asymptomatic amyloid-related
      imaging abnormalities increased in a dose- and APOE epsilon4 genotype-dependent
      manner. Exploratory analyses suggested a dose-dependent drug effect on clinical
      and biomarker endpoints. CONCLUSIONS: The study was stopped early for futility,
      but dose-dependent effects observed in exploratory analyses on select clinical
      and biomarker endpoints suggest that higher dosing with gantenerumab may be
      necessary to achieve clinical efficacy. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01224106 . Registered on October 14, 2010.

PMID- 29221493
TI  - Caring for a cerebral palsy child: a caregivers perspective at the University
      Teaching Hospital, Zambia.
AB  - BACKGROUND: Cerebral palsy is a major cause of disability and most survivors are
      left with residual disability and are dependent on parents/caregivers for
      essential care. This study aimed to determine the experiences of
      parents/caregivers of cerebral palsy children receiving out-patient
      physiotherapy. A concurrent mixed methods was used to collect data in the present
      study. The modified caregiver strain index (MCSI-13) was used to detect Disturbed
      sleep, Inconvenient/Tiresome, Physical strain, Confining, Family changes, Changes
      in personal plan, Other demands, Emotional adjustments, Upsetting behavior,
      Patient has changed, Work adjustments, Financial Strain and Feeling Overwhelmed
      (strain morbidity) in 25 parents/caregivers of CP children. A purposive sample of
      25 parents/caregivers was selected for both the quantitative part and qualitative
      part of the study. The study was conducted at Community Based Intervention
      Association Out-patients at the University Teaching Hospital in Lusaka, Zambia.
      The MCSI was used to collect quantitative data and in-depth interviews provided
      the qualitative data. RESULTS: The median age of the participants was 33.6 years
      and a range of 27 to 50 years. The study sample consisted of more females (92%)
      than males (8%). being overwhelmed and inconvenient/tiresome followed by family
      adjustments and work adjustment 72 and 68% respectively for each were the
      experiences mostly highlighted by the parents/caregivers in this study. When it
      came to the needs of the parents/caregivers more than half of them needed help
      with caring. To this effect participants expressed their perception; one mother
      had this to say, "...I need someone to help in caring. Sometimes I need to do
      some other things but can't, because if I do then no one will remain with the
      child...". CONCLUSION: This study point out to some evidence that the burden
      inflicted on those caring for children with cerebral palsy should be addressed if
      the quality of care for those with cerebral palsy is to be improved.

PMID- 29221494
TI  - Factors associated with the achievement of cervical smears by general
      practitioners.
AB  - OBJECTIVE: Reliable data about general practitioners performing pap-tests are
      insufficient. A claim code for the achievement of pap-smears exists in France,
      but its use by general practitioners is not known. The main purpose of this study
      was to highlight independent factors associated with the achievement of pap
      smears by the general practitioner (GP). We carried out a descriptive and
      analytic epidemiologic study in 347 GPs and their 244,889 patients, registered at
      the Health Care Insurance Fund of Flanders. The European Deprivation Index (EDI)
      in the area of GP's surgeries was specified. All GPs were questioned by telephone
      about their performance of pap-tests. The claim database of the insurance fund
      was analyzed to describe characteristics of GPs. RESULTS: The answer rate among
      questioned GPs was 98.8%. Pap-smears were performed in their surgeries by 182 GPs
      (53.1%). Among males, 45.7% performed pap-smears versus 78.4% of the female
      (adjusted odds-ratio = 4.5, p < 0.001). The mean rate of screened women in the
      target population was 44% when GPs were performing smears versus 42% when they
      were not (adjusted odds-ratio = 1.04, p = 0.03). Only 19.5% of GPs used the claim
      code. The number of patients, and the EDI were not associated with pap-smears.
      Trial registration ClinicalTrials.gov NCT02749110 (April 22, 2016).

PMID- 29221495
TI  - Bivariate longitudinal data analysis: a case of hypertensive patients at Felege
      Hiwot Referral Hospital, Bahir Dar, Ethiopia.
AB  - OBJECTIVE: Longitudinal data are often collected to study the evolution of
      biomedical markers. The study of the joint evolution of response variables
      concerning hypertension over time was the aim of this paper. A hospital based
      retrospective data were collected from September 2014 to August 2015 to identify
      factors that affect hypertensive. The joint mixed effect model with unstructured
      covariance was fitted. A total of 172 patients screened for antihypertensive
      drugs treated were longitudinally considered from Felege Hiwot referral. RESULTS:
      The joint mixed effect model with unstructured covariance (AIC: 12,236.9 with
      [Formula: see text] = 1007.8, P < 10-4) was significantly best fit to the data.
      The correlation between the evolutions of DBP and SBP was 0.429 and the evolution
      of the association between responses over-time was found 0.257. Among all
      covariates included in joint-mixed-effect-models, sex, residence, related disease
      and time were statistically significant on evolution of systolic and diastolic
      blood pressure. The joint modeling of longitudinal bivariate responses is
      necessary to explore the association between paired response variables like
      systolic and diastolic blood pressure. Fitting joint model with modern computing
      method is recommended to address questions for association of the evolutions with
      better accuracy.

PMID- 29221497
TI  - Low serum ferritin and G6PD deficiency as potential predictors of anaemia in
      pregnant women visiting Prime Care Hospital Enugu Nigeria.
AB  - OBJECTIVES: Though iron deficiency is known to be a major risk factor of anaemia,
      the association of G6PD deficiency and malaria with anaemia still remains
      unclear. Hence, a cross-sectional study involving 95 pregnant women visiting
      Prime Care Hospital in Trans-Ekulu region of Enugu Nigeria was conducted to
      determine possible predictors of anaemia in pregnancy. RESULTS: The prevalence of
      anaemia, malaria and G6PD deficiency were 53.7, 12.6 and 60% respectively. Low
      serum ferritin (OR 5.500, CI 2.25-13.42, p < 0.05) and G6PD deficiency (OR 0.087,
      CI 0.03-0.23, p < 0.05) were associated with anaemia in pregnancy. On the other
      hand, malaria did not significantly associate (OR 1.184, CI 0.35-3.97, p = 0.964)
      with anaemia in pregnant women. These findings showed high prevalence of anaemia
      among pregnant women with low serum ferritin level and G6PD deficiency as high
      risk factors of anaemia.

PMID- 29221496
TI  - Does intensive management improve remission rates in patients with intermediate
      rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing
      disability and reduced quality of life over time. 'Treating to target' has been
      shown to be effective in active established disease and also in early disease.
      However, there is a lack of nationally agreed treatment protocols for patients
      with established rheumatoid arthritis who have intermediate disease activity.
      This trial is designed to investigate whether intensive management of disease
      leads to a greater number of remissions at 12 months. Levels of disability and
      quality of life, and acceptability and cost-effectiveness of the intervention
      will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised,
      open-label, two-arm, parallel-group, multicentre trial undertaken at specialist
      rheumatology centres across England. Three hundred and ninety-eight patients with
      established rheumatoid arthritis will be recruited. They will currently have
      intermediate disease activity (disease activity score for 28 joints assessed
      using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active
      joints) and will be taking at least one disease-modifying anti-rheumatic drug.
      Participants will be randomly selected to receive intensive management or
      standard care. Intensive management will involve monthly clinical reviews with a
      specialist health practitioner, where drug treatment will be optimised and an
      individualised treatment support programme delivered based on several principles
      of motivational interviewing to address identified problem areas, such as pain,
      fatigue and adherence. Standard care will follow standard local pathways and will
      be in line with current English guidelines from the National Institute for Health
      and Clinical Excellence. Patients will be assessed initially and at 6 and 12
      months through self-completed questionnaires and clinical evaluation. DISCUSSION:
      The trial will establish whether the known benefits of intensive treatment
      strategies in active rheumatoid arthritis are also seen in patients with
      established rheumatoid arthritis who have moderately active disease. It will
      evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL
      REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16
      January 2014.

PMID- 29221498
TI  - Influence of community-based education on undergraduate health professions
      students' decision to work in underserved areas in Uganda.
AB  - BACKGROUND: Uganda is beset by a shortage of health workers and the few available
      are mal-distributed. Providing rural exposure through community-based education
      could positively influence students' perspectives towards work in rural areas. We
      aimed to assess the impact of Community-Based Education and Research (COBERS) on
      health professions students' attitudes towards working in rural areas. This was a
      before-and-after study among 525 students of 4 medical universities in Uganda.
      Data was collected using self-administered paper-based questionnaires. Logistic
      regression and Poisson regression respectively were used to assess intention and
      intended number of years of work in rural areas. RESULTS: Before COBERS, 228/518
      (44.0%) students indicated that they intended to work in rural areas as compared
      to 245/506 (48.4%) after the COBERS placement. Before the COBERS placement, the
      factors that were associated with students considering to work in a rural area
      were: extra allowance (OR = 0.2; 95% CI 0.1-0.6), and availability of social
      amenities (OR = 0.2; 95% CI 0.1-0.7). After their COBERS placement, the factors
      were: access to long distance courses (OR = 2.0; 95% CI 1.0-3.7) and being posted
      to a facility in a rural area (OR = 15.0; 95% CI 6.5-35.5). Before the COBERS
      placement the factors that influenced how long students thought they would be
      willing to work in a rural environment were: reliable electricity (IRR = 0.6; 95%
      CI 0.3-1.0) and Internet (IRR = 1.5; 95% CI 1.0-2.3), high salary (IRR = 0.4; 95%
      CI 0.3-0.7), and having skills to practice in rural settings (IRR = 2.0; 95% CI
      1.3-3.1). Reliable electricity (IRR = 0.5; 95% CI 0.3-0.8) and long distance
      courses (IRR = 2.1; 95% CI 1.4-3.1) were significant motivators after having
      undergone the COBERS placement. CONCLUSIONS: The majority of health professions
      students do not intend to work in rural areas after they graduate. Improving the
      welfare of health professionals working in rural areas could attract more health
      professionals to rural areas thus addressing the maldistribution of health
      workers in Uganda.

PMID- 29221500
TI  - Analysis of Naturally Occurring Resistance-Associated Variants to NS3/4A Protein
      Inhibitors, NS5A Protein Inhibitors, and NS5B Polymerase Inhibitors in Patients
      With Chronic Hepatitis C.
AB  - The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and
      boceprevir were approved in 2011, and both NS5A and NS5B polymerase inhibitors
      were launched. Recently, direct-acting antivirals (DAAs) have had a major impact
      on patients infected with HCV. HCV DAAs are highly effective antivirals with
      fewer side effects. DAAs have been developed for the treatment of HCV infection
      in combination with PEG-IFN-alpha/RBV as well as in IFN-free regimens. However,
      some drug resistance mutations occur when a single oral DAA is used for
      treatment, which indicates that there is a low-frequency drug resistance mutation
      in HCV patients before the application of antiviral drugs. Our research showed
      that natural resistance to HCV DAAs was found in treatment-naive CHC patients and
      that the drug resistance mutation rates differ in various HCV genotypes. Many
      challenges posed by natural resistance should be considered in the context of DAA
      therapies.

PMID- 29221499
TI  - An unusual osteoma in the mandibular condyle and the successful replacement of
      the temporomandibular joint with a custom-made prosthesis: a case report.
AB  - BACKGROUND: An osteoma is a benign tumor of bone with unknown etiology and is
      considered rare, mostly restricted to the craniofacial skeleton. CASE
      PRESENTATION: This case report describes an uncommon condylar osteoma in a 67
      years old white female patient with laterognathism to the left side, limited
      mouth opening, aesthetic change and pain associated with the right
      temporomandibular joint (TMJ). The histopathological examination confirmed
      osteoma. The lesion was surgically excised and immediate reconstruction was
      carried out using a custom-made total TMJ prosthesis. The patient has been in
      follow-up for 2 years, with no symptoms. CONCLUSIONS: Unilateral total TMJ
      prosthesis can be considered to replacement of TMJ after osteoma excision with
      resection of the condyle.

PMID- 29221501
TI  - Lean Methodology Reduces Inappropriate Use of Antipsychotics for Agitation at a
      Psychiatric Hospital.
AB  - OBJECTIVE: To Evaluate the Effects of Applying Lean Methodology-Improving Quality
      Increasing Efficiency by Eliminating Waste and Reducing Costs-An Approach To
      Decrease the Prescribing Frequency of Antipsychotics for The Indication of
      Agitation. DESIGN: Historically Controlled Study. SETTING: Bheppard Pratt Health
      System is the Largest Private Provider of Psychiatric Care in Maryland With a
      Total Bed Capacity of 300. There Were 4 337 Patient Days From November 1 2012 to
      October 31 2013 on the Dementia Unit. PATIENTS: All Patients Admitted on the
      Dementia Unit Were 65 Years of Age and Older with a Primary Diagnosis of
      Dementia. INTERVENTION: our Multidisciplinary Team Used Lean Methodology to
      Identify the Root Causes and Interventions Necessary to Reduce Inappropriate
      Antipsychotic Use. MAIN OUTCOME MEASURES: The Primary Outcome Was Rate of
      Inappropriately Indicating Agitation as the Rationale When Prescribing
      Antipsychotic Medications. RESULTS: There Was a 90% (P < 0.001) Reduction in Rate
      Of Antipsychotic Prescribing with an Indication of Agitation. CONCLUSION: The
      Lean Methodology Interventions Led To A 90% (P < 0.001) Reduction in the Rate of
      Antipsychotic Prescribing with an Indication of Agitation and a 10% Rate
      Reduction in Overall Antipsychotic Prescribing. Key Words: Agitation Alzheimer's
      Antipsychotics Behavioral and Psychological Symptoms of Dementia Centers For
      Medicare & Medicaid Services Dementia Root-cause Analysis. ABBREVIATIONS: BPSD =
      Behavioral and Psychological Symptoms of Dementia CATIE-AD = Clinical
      Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease EMR =
      Electronic Medical Records GAO = Government Accountability Office GNCIS =
      Geriatric Neuropsychiatric Clinical Indicator Scale.

PMID- 29221502
TI  - Impact of Cardiorespiratory Fitness on Frequency of Atrial Fibrillation, Stroke,
      and All-Cause Mortality.
AB  - Benefits of cardiorespiratory fitness on cardiovascular health are well
      recognized, but the impact on incidence of atrial fibrillation (AF) and stroke,
      and, particularly, risk of stroke and mortality in patients with AF is less
      clear. From 1993 to 2010, patients referred for a treadmill exercise test (TMET)
      at the Mayo Clinic Rochester, MN, were retrospectively identified (N = 76,857).
      From this, 14,094 local residents were selected. Exclusions were age <18 years;
      history of heart failure, structural or valvular heart disease, AF or flutter, or
      stroke. Subjects were divided into 4 groups at baseline based on quartiles of
      functional aerobic capacity (FAC) and followed through January 2016. The final
      study cohort included 12,043 patients. During median follow-up of 14 (9 to 17)
      years, 1,222 patients developed incident AF, 1,128 developed stroke, and 1,590
      patients died. Each 10% increase in FAC was associated with decreased risk of
      incident AF, stroke, and mortality by 7% (0.93 [0.91 to 0.96, p < 0.001]), 8%
      (0.92 [0.89 to 0.94, p < 0.001]), and 16% (0.84 [0.82 to 0.86, p < 0.001]),
      respectively. In patients who developed incident AF with baseline FAC <75% versus
      >=105%, risks of both stroke (1.40 [1.04 to 1.90, p = 0.01]) and mortality (3.20
      [2.11 to 4.58, p < 0.001]) were significantly higher. In conclusion, better
      cardiorespiratory fitness is associated with lower risk of incident AF, stroke,
      and mortality. Similarly, risk of stroke and mortality in patients with AF is
      also inversely associated with cardiorespiratory fitness.

PMID- 29221503
TI  - Editorial.

PMID- 29221504
TI  - A social identity analysis of responses to economic inequality.
AB  - Even though there is growing awareness that economic inequality is harmful for
      people's health, the way that such inequality affects social behavior and
      political attitudes remains poorly understood. Moving beyond a focus on the
      health and well-being costs of income inequality, we review research that
      examines how economic inequality shapes dynamics between groups within societies,
      addressing the questions why, when, and for whom inequality affects social
      behavior and political attitudes. On the basis of classic social identity
      theorizing, we develop five hypotheses that focus on the way inequality shapes
      the fit of wealth categorizations (H1), intergroup relations (H2), and
      stereotypes about wealth groups (H3). We also theorize how the effects of
      inequality are moderated by socio-structural conditions (H4) and socio-economic
      status (H5). Together, these hypotheses provide a theoretically informed account
      of the way in which inequality undermines the social fabric of society and
      negatively affects citizen's social and political behavior.

PMID- 29221505
TI  - The politics of socioeconomic status: how socioeconomic status may influence
      political attitudes and engagement.
AB  - Socioeconomic status is hypothesized to be one factor informing political
      attitudes and actions. Presumably, this relationship is rooted in economic self
      interest, with individuals preferring policies that would benefit them
      financially. In addition, these economic policy preferences are assumed to
      translate into political action. However, the relationships between socioeconomic
      status and political attitudes and behavior, as well as the psychological
      mechanisms associated with those relationships, are not straightforward. Here, we
      briefly review the current state of knowledge on the relationships between
      socioeconomic status and political attitudes and behavior. Overall, the research
      suggests that while socioeconomic status informs political attitudes toward
      economic policies, these attitudes may not correlate with complementary political
      behavior.

PMID- 29221506
TI  - Inequality and well-being.
AB  - Income inequality is on the rise across the globe - an increasingly small portion
      of individuals control an increasingly large portion of wealth. Importantly, this
      inequality is associated with lower levels of happiness for citizens. In this
      paper, we review evidence regarding the psychological nature of this
      relationship. We examine central mechanisms that explain the link between income
      inequality and subjective well-being, including anxiety from status competition,
      mistrust, and hopes and fears about the future. We stress that perceptions of
      inequality matter as much as objective measures for well-being. Finally, we
      suggest some potential areas for future research regarding inequality and
      happiness and advise that this body of work be considered when developing and
      evaluating relevant policies.

PMID- 29221507
TI  - (Mis)perceptions of inequality.
AB  - Laypeople's beliefs about the current distribution of outcomes such as income and
      wealth in their country influence their attitudes toward issues ranging from
      taxation to healthcare - but how accurate are these beliefs? We review the
      burgeoning literature on (mis)perceptions of inequality. First, we show that
      people on average misperceive current levels of inequality, typically
      underestimating the extent of inequality in their country. Second, we delineate
      potential causes of these misperceptions, including people's overreliance on cues
      from their local environment, leading to their erroneous beliefs about both the
      overall distributions of wealth and income and their place in those
      distributions. Third, we document that these (mis)perceptions of inequality - but
      not actual levels of inequality - drive behavior and preferences for
      redistribution. More promisingly, we review research suggesting that correcting
      misperceptions influences preferences and policy outcomes.

PMID- 29221508
TI  - Social power and social class: conceptualization, consequences, and current
      challenges.
AB  - This article offers a primer on social power and social class with respect to
      their theoretical importance, conceptual distinction, and empirical relationship.
      We introduce and define the constructs of social power, social class, and one's
      psychological sense of power. We next explore the complex relationship between
      social power and social class. Because social class can produce a sense of power
      within an individual, studies on social power can inform theory and research on
      social class. We conclude with a discussion of the current challenges and future
      opportunities for the study of social power and social class.

PMID- 29221509
TI  - The consequences of economic threat for motivated social cognition and action.
AB  - Economic threat (e.g., low or precarious socio-economic status) motivates social
      psychological responses to restore or maintain a sense of control and self
      esteem, thwarted under conditions of personal or collective economic crisis. We
      review recent research showing that these processes elicit personal or collective
      attitudes and action tendencies that may either contribute to alleviate the
      source of the threat (e.g., collective action toward equality) or to be merely
      palliative (e.g., displaced intergroup conflict, ethnic prejudice). Further
      research should focus more on testing the motivational processes underlying the
      effects of economic threat.

PMID- 29221510
TI  - Theory from the South: a decolonial approach to the psychology of global
      inequality.
AB  - Hegemonic understandings rooted in the epistemic perspectives of the Global North
      explain global inequality (i.e., unequal relations between Global North and
      South) as a developmental gap in progress toward Eurocentric modernity. From this
      perspective, global inequality exists because Northern societies have created
      modern institutions and mentalities (e.g., independent selfways) that have
      enabled them to achieve development, and Southern societies suffer from poverty
      because their institutions and associated mentalities (e.g., interdependent
      selfways) retard development. In contrast, a decolonial standpoint, rooted in
      epistemic perspectives of the Global South, emphasizes the coloniality of modern
      individualist mentalities: the extent to which they reflect and reproduce
      colonial violence. From this perspective, modern individualist mentalities are a
      source, rather than solution, of global inequality, and a more equitable world
      requires cultivation of mentalities attuned to the interdependence of everyday
      life.

PMID- 29221511
TI  - How social-class stereotypes maintain inequality.
AB  - Social class stereotypes support inequality through various routes: ambivalent
      content, early appearance in children, achievement consequences,
      institutionalization in education, appearance in cross-class social encounters,
      and prevalence in the most unequal societies. Class-stereotype content is
      ambivalent, describing lower-SES people both negatively (less competent, less
      human, more objectified), and sometimes positively, perhaps warmer than upper-SES
      people. Children acquire the wealth aspects of class stereotypes early, which
      become more nuanced with development. In school, class stereotypes advantage
      higher-SES students, and educational contexts institutionalize social-class
      distinctions. Beyond school, well-intentioned face-to-face encounters ironically
      draw on stereotypes to reinforce the alleged competence of higher-status people
      and sometimes the alleged warmth of lower-status people. Countries with more
      inequality show more of these ambivalent stereotypes of both lower-SES and higher
      SES people. At a variety of levels and life stages, social-class stereotypes
      reinforce inequality, but constructive contact can undermine them; future efforts
      need to address high-status privilege and to query more heterogeneous samples.

PMID- 29221512
TI  - Social class and prosocial behavior: current evidence, caveats, and questions.
AB  - This review synthesizes research on social class and prosocial behavior.
      Individuals of lower social class display increased attention to others and
      greater sensitivity to others' welfare compared to individuals of higher social
      class, who exhibit more self-oriented patterns of social cognition. As a result,
      lower-class individuals are more likely to engage in other-beneficial prosocial
      behavior, whereas higher-class individuals are more prone to engage in self
      beneficial behavior. Although the extant evidence indicates that higher social
      class standing may tend to undermine prosocial impulses, we propose that the
      effects of social class on prosocial behavior may also depend on three crucial
      factors: motivation, identity, and inequality. We discuss how and why these
      factors may moderate class differences in prosociality and offer promising lines
      of inquiry for future research.

PMID- 29221513
TI  - Life Expectancy, Causes of Death, Risk Factors in China and the U.S.

PMID- 29221514
TI  - Yield of Brain MRI in Clinically Diagnosed Epilepsy in the Kingdom of Bhutan: A
      Prospective Study.
AB  - BACKGROUND: People with epilepsy (PWE) in low- and middle-income countries may
      not access the health resources that are considered optimal for epilepsy
      diagnosis. The diagnostic yield of magnetic resonance imaging (MRI) has not been
      well studied in these settings. OBJECTIVES: To report the diagnostic yield of
      brain MRI and identify clinical associations of abnormal MRI findings among PWE
      in a neurocysticercosis-endemic, resource-limited setting and to identify the
      proportion and putative structural brain causes of drug-resistant epilepsy.
      METHODS: PWE were prospectively enrolled at the Jigme Dorji Wangchuck National
      Referral Hospital in Bhutan (2014-2015). Each participant completed clinical
      questionnaires and a 1.5-Tesla brain MRI. Each MRI was reviewed by at least 1
      radiologist and neurologist in Bhutan and the United States. A working definition
      of drug-resistant epilepsy for resource-limited settings was given as (a)
      seizures for >1 year, (b) at least 1 seizure in the prior year, and (c) presently
      taking 2 or more antiepileptic drugs (AEDs). Logistic regression models were
      constructed to test the cross-sectional association of an abnormal brain MRI with
      clinical variables. FINDINGS: A total of 217 participants (125 [57%] female; 54
      [25%] < 18 years old; 199 [92%] taking AEDs; 154 [71%] with a seizure in the
      prior year) were enrolled. There was a high prevalence of abnormal brain MRIs
      (176/217, 81%). Mesial temporal sclerosis was the most common finding (n = 115,
      53%, including 24 children), exceeding the number of PWE with neurocysticercosis
      (n = 26, 12%, including 1 child) and congenital/perinatal abnormalities (n = 29,
      14%, including 14 children). The number of AEDs (odds ratio = .59, P = .03) and
      duration of epilepsy (odds ratio = 1.11, P = .02) were significantly associated
      with an abnormal MRI. Seizure in the prior month was associated with the presence
      of mesial temporal sclerosis (odds ratio = .47, P = .01). A total of 25 (12%)
      participants met our definition of drug-resistant epilepsy, with mesial temporal
      sclerosis (n = 10), congenital malformations (n = 5), and neurocysticercosis (n =
      4) being the more common findings. CONCLUSIONS: The prevalence of abnormalities
      on brain MRI for PWE in resource-limited settings is high as a result of a
      diffuse range of etiologies, most commonly mesial temporal sclerosis. Drug
      resistant epilepsy accounted for 12% of the referral population in a conservative
      estimation.

PMID- 29221516
TI  - Transculturalizing Diabetes Prevention in Latin America.
AB  - BACKGROUND: Type 2 diabetes (T2D) imposes a heavy burden in developing countries,
      requiring effective primary prevention policies. Randomized clinical trials have
      identified successful strategies in T2D prevention. However, translating these
      results to real-life scenarios and adapting to ethnocultural differences is a
      major challenge. Transculturalization allows incorporating cultural factors to
      diabetes prevention strategies to optimize implementation of clinical trials
      results. The purpose of this paper is to review the transcultural adaptations
      developed for T2D prevention in Latin America (LA). METHODS: A comprehensive
      literature review spanning 1960-2016 was performed, using "Diabetes," "Latin
      America," "Prevention," "Screening," and "Tools" as key words. RESULTS: Two major
      tasks are underway in LA: adaptation of screening tools for high-risk
      individuals, and implementation of diabetes prevention programs. The Finnish
      Diabetes Risk Score (FINDRISC) is the most widely used screening tool to detect
      new cases of T2D and people with prediabetes, and it has been adapted (LA
      FINDRISC) to include the waist circumference cutoff values appropriate for LA
      population (>=94 cm for men and >=90 cm for women). The validation of the LA
      FINDRISC performance depends on the local characteristics. A LA-FINDRISC score
      >10 may be the best cutoff to identify individuals with impaired glucose
      regulation in population-based studies, but a higher score (>12-14) might be more
      appropriate in a clinical setting. A shorter version of the FINDRISC using only
      the 4 variables with highest impact has been developed and validated in Colombia
      (ColDRISC). The translation of the Diabetes Prevention Program study in a Latino
      population in Venezuela found a significant improvement in cardiometabolic risk
      factors. An adaptation of the Diabetes Prevention Study in the DEMOJUAN study in
      Barranquilla, Colombia, reduced 2-hour postload glucose. CONCLUSION: Successful
      transculturalization strategies have been implemented in screening tools and
      prevention programs in LA.

PMID- 29221515
TI  - Socioeconomic Disparities in the Prevalence of Cardiometabolic Risk Factors in
      Ghanaian Women.
AB  - BACKGROUND: Recent trends toward urbanization in developing countries like Ghana,
      coupled with nutritional transition and aging populations, have led to a rapid
      increase in the prevalence of noncommunicable diseases such as obesity, diabetes,
      and hypertension. The purpose of this study was to evaluate the association
      between socioeconomic status and cardiometabolic risk factors among women in
      Ghana. METHODS: Data for this analysis were obtained from Wave 1 of the Ghana
      Study of Global Aging and Health, conducted in 2007, and included women 18 years
      and older. Survey weighted descriptive and multivariable linear regression models
      were used to examine the association between socioeconomic status and
      cardiometabolic risk factors. RESULTS: Among a total of 1988 women, 48% ages 40
      64 years, almost half were overweight or obese (47%) and 21% had current
      hypertension, whereas only 4.3% and 2% of women self-reported a history of
      hypertension and diabetes, respectively. Multivariable adjusted analysis
      indicated that women with a high school education had 2-fold increased odds of
      being overweight or obese compared with those with no formal education (odds
      ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20-3.42). Women employed in the
      public sector had almost a 5 times higher odds of being overweight or obese (OR:
      4.94, 95% CI: 1.42-17.15), whereas those employed in the private sector or self
      employed had reduced odds of diabetes (OR: 0.27, 95% CI: 0.10-0.70) and
      hypertension (OR: 0.43, 95% CI: 0.21-0.86). CONCLUSION: The prevalence of
      cardiometabolic risk factors varies by socioeconomic status among Ghanaian women.
      Targeted intervention programs to reduce overweight and obesity may begin among
      Ghanaian women employed in the public sector, and improved access to health care
      will be critical for timely diagnosis and management of other disease risk
      factors.

PMID- 29221517
TI  - Urban-Rural Disparity in Helicobacter Pylori Infection-Related Upper
      Gastrointestinal Cancer in China and the Decreasing Trend in Parallel with
      Socioeconomic Development and Urbanization in an Endemic Area.
AB  - BACKGROUND: Globally China has the largest urban-rural disparity in socioeconomic
      development, and the urban-rural difference in upper gastrointestinal cancer
      (UGIC) is similar to the difference between developed and developing countries.
      OBJECTIVES: To describe urban-rural disparity in UGIC and to emphasize prevention
      by socioeconomic development and urbanization in China. METHODS: Age-standardized
      incidence rates (ASRs) of cancers in 2012 were compared between urban
      Shijiazhuang city and rural Shexian County, and trends from 2000-2015 in Shexian
      County were analyzed. FINDINGS: Compared with urban Shijiazhuang city, the ASR of
      gastroesophageal cancers in rural Shexian County was 5.3 times higher in men
      (234.1 vs 44.2/100,000, P < .01) and 9.1 times higher in women (107.7 vs
      11.8/100,000, P < .01). This rural-urban disparity in UGIC is associated with
      differences in socioeconomic development in annual gross domestic product (GDP)
      per capita of US$2700 vs US$6965, in urbanization rate of 48% vs 100%, and in
      adult Helicobacter pylori infection prevalence of 75% vs 50%. From 2000-2015, the
      GDP per capita in Shexian County increased from US$860 to US$3000, urbanization
      rate increased from 22.4% to 54.8%, and prevalence of H pylori infection among 3-
      to 10-year-old children decreased from 60% to 46.1% (P < .01). Meanwhile, the
      biennial ASR of esophagogastric cancer decreased 42% in men, from 313.5 to 182.1
      per 100,000 (P < .01), and 57% in women, from 188.6 to 80.4 per 100,000 (P =
      .00). However, lung, colorectal, and gallbladder cancers and leukemia in both
      sexes and breast, ovary, thyroid, and kidney cancer in women increased
      significantly. Despite this offset, ASR of all cancers combined decreased 25% in
      men (from 378.2 to 283.0/100,000, P = .00) and 19% in women (from 238.5 to
      193.6/100,000, P = .00). CONCLUSIONS: Urban-rural disparity in UGIC is related to
      inequity in socioeconomic development. Economic growth and urbanization is
      effective for prevention in endemic regions in China and should be a policy
      priority.

PMID- 29221518
TI  - Measuring Healthy Lifestyle and Mental Health Indicators in South Asian Women
      Using the "Your Health: Quality of Life and Well-Being" Questionnaire.
AB  - INTRODUCTION: Health is a state of complete physical, mental, and social well
      being and not merely the absence of disease or infirmity. A literature review has
      revealed that there is no specific questionnaire available to assess well-being
      within the community. METHODS: Fifty South Asian women were randomly selected to
      complete the "Your Health: Quality of Life and Well-being Questionnaire"
      assessing diet, lifestyle, and mental health among others. Data from the
      questionnaires was extracted and participants were categorised based on these
      findings. RESULTS: This tool has positively identified a number of key risk
      factors for poor health, symptoms associated with mental illness, and the burden
      of comorbidities within the assessed cohort. Sixty-three percent of the women had
      an unhealthy body mass index (BMI), over half did not know the maximum limit of
      salt per day, and almost one-fourth had multiple health conditions. CONCLUSIONS:
      This questionnaire is an effective tool to use within the community. There is a
      significant burden of obesity, complicated by poor lifestyle habits and
      significant mood and anxiety symptoms within the studied South Asian population.

PMID- 29221519
TI  - Addressing Noncommunicable Disease on Short-Term Medical Trips: A Longitudinal
      Study of Hypertension Treatment in Santo Domingo.
AB  - BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality
      worldwide and pose complex challenges in developing nations. Short-term medical
      trips, which often operate independently of government and pharmaceutical
      companies, are in a unique position to address NCDs in developing nations. In
      2010, the Dominican Aid Society of Virginia shifted the focus of their semiannual
      clinic to addressing NCDs in Paraiso, Santo Domingo. OBJECTIVE: This study
      analyzes the longitudinal impact of a short-term medical trip on the control of
      hypertension in their patient population. METHODS: Returning patients were
      identified through a review of medical records from 2014 and 2016. A sample of
      patients who only visited in either 2014 or 2016 were matched on sex and age and
      served as an internal comparison group. A generalized linear mixed model was
      applied to assess changes in blood pressure, the proportion of patients receiving
      blood pressure treatment, and the intensity of blood pressure treatment within
      and between returning and new patients over the study period. FINDINGS: There was
      a significant decrease in diastolic blood pressure within returning patients.
      Change in systolic blood pressure was significantly different between returning
      and new patients, with improvement in returning patients. There was a significant
      increase in the proportion of new patients receiving blood pressure treatment and
      a higher intensity of blood pressure treatment over time. The change in the
      proportion of patients receiving blood pressure treatment in the new patient
      group was significantly higher than that of the returning patient group.
      CONCLUSIONS: Short-term medical trips with a recurrent presence in a community
      may improve control of hypertension and other NCDs in developing nations. Further
      research into the impact that short-term medical trips may have on NCDs is
      needed.

PMID- 29221520
TI  - Disability Characteristics of Community-Based Rehabilitation Participants in
      Kayunga District, Uganda.
AB  - BACKGROUND: Approximately 80% of individuals with disability reside in low- and
      middle-income countries where community-based rehabilitation (CBR) has been used
      as a strategy to improve disability. However, data relating to disability
      severity among CBR beneficiaries in low-income countries like Uganda remain
      scarce, particularly at the community or district level. OBJECTIVES: To describe
      severity of disability and associated factors for persons with physical
      disabilities receiving CBR services in the Kayunga district of Uganda. METHODS: A
      cross-sectional sample of 293 adults with physical disabilities receiving a CBR
      service in the Kayunga district was recruited. Disability severity was measured
      using the 12-item World Health Organization Disability Assessment Schedule 2.0
      (WHODAS2.0), and analyzed as a binary outcome (low: 0-9, high: 10-48).
      Inferential statistics using odds ratios were used to determine factors
      associated with impairment severity. FINDINGS: The mean WHODAS 2.0 score of
      persons with physical disabilities was 12.7 (standard deviation = 8.3). More than
      half (52.90%) of people with physical disabilities reported a high level of
      functional impairment. Increased disability severity was significantly associated
      with limited access to assistive devices (adjusted odds ratio [AOR] = 4.55, 95%
      confidence interval [CI]: 1.87-14.08, P < .001), and increased use of medical
      health care (AOR = 5.55, 95% CI: 1.84-16.79, P = .002). CONCLUSION: These
      findings suggest a high level of moderate to severe functional impairments in
      persons with physical disabilities receiving CBR in Kayunga district. These data
      provide support for efforts to enhance CBR's ability to liaise with local health
      care, education, and community resources to promote access to needed services and
      ultimately improve the functional status of persons with disabilities in low
      resource settings.

PMID- 29221521
TI  - China's Efforts on Management, Surveillance, and Research of Noncommunicable
      Diseases: NCD Scorecard Project.
AB  - BACKGROUND: The incidence of noncommunicable diseases (NCDs) is rising
      dramatically throughout the world. Aspects of researches concerned with the
      improvement and development of prevention and control of NCDs have been
      conducted. Furthermore, the influence of most determinants of the major NCDs has
      showed that a broad and deep response involving stakeholders in different sectors
      is required in the prevention and control of NCDs. OBJECTIVE: China has
      experienced an increase in NCDs in a short period compared with many countries.
      To address the burden of NCDs in China, it is important to learn about the
      progress that has been made in prevention and control of NCDs in China and
      worldwide, informed by opinions of stakeholders in different areas. METHODS: In
      2014, GRAND South developed the NCD Scorecard instrument to evaluate progress of
      NCD prevention and control in 23 countries through a 2-round Delphi process. The
      scorecard included 51 indicators in 4 domains: governance, surveillance and
      research, prevention and risk factors, and health system response. Stakeholders
      were then selected in the areas of government, nongovernmental organizations,
      private sectors, and academia to join the NCD Scorecard survey. Indicators of
      progress were scored by stakeholders from 0 (no activity), 1 (present but not
      adequate), and 2 (adequate) to 3 (highly adequate) and then the percentage of
      progress in each domain was calculated, representing the current situation in
      each country. FINDINGS: There were 14 indicators in the domains of governance and
      surveillance and research. Of 429 stakeholders worldwide, 41 in China
      participated in the survey. China scored in the top 5 out of all participating
      countries in those 2 domains, scoring 67% in governance and 64% in surveillance
      and research. Indicators on which China scored particularly well included having
      a well-resourced unit or department responsible for NCDs, having a strong
      national system for recording the cause of all deaths, and having a system of NCD
      surveillance. Areas where China had the greatest need for improvement included
      increasing taxes on tobacco and addressing the needs of the population older than
      age 70 dying from major NCDs. CONCLUSION: In China the burden of disease of NCDs
      and disabilities remains serious, although China has put significant efforts into
      its governance and surveillance and research. To improve, further action is
      needed on reducing tobacco consumption, increasing investment in the national
      health budget, and increasing the focus on system construction.

PMID- 29221522
TI  - Barriers to Smoking Cessation Among Drug-Resistant Tuberculosis Patients in South
      Africa.
AB  - BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a significant cause of
      morbidity and mortality. The long-term health effects of smoking and the risk of
      adverse TB outcomes, including increased periods of infectiousness, have been
      reported among DR-TB patients in South Africa. OBJECTIVES: This study aimed to
      identify the barriers to smoking cessation among DR-TB inpatients at a hospital
      in Durban, South Africa. METHODS: A qualitative design using in-depth interviews
      with a purposive sample of 20 DR-TB inpatients was employed. The sample included
      15 men and 5 women aged 18-70 years who self-identified as smokers. Open-ended
      questions were used to explore barriers militating against smoking cessation
      among this sample. Data were analyzed with the aid of the software QSR NVivo10.
      FINDINGS: Personal and structural-level barriers (factors) to smoking cessation
      were identified. Personal factors included addiction and non-addiction-related
      barriers. Addiction-related barriers included smoking history, cravings for a
      cigarette, smoking as part of a daily routine, and failed quit attempts. Non
      addiction-related barriers included lack of knowledge about quit strategies,
      psychosocial stress, lack of the willpower to quit smoking, and the influence of
      peers. Structural barriers included ineffective health education programs, lack
      of extramural activities when on admission in hospital leading to a lot of spare
      time, lack of smoking cessation interventions, and access to cigarettes within
      and around the hospital environment. Patients expressed interest in smoking
      cessation and conveyed their frustration at the lack of appropriate support to do
      so. CONCLUSIONS: The findings reiterate the need for smoking cessation
      intervention to be incorporated as an integral component of DR-TB management in
      South Africa. Many patients expressed an interest in pharmacological aids and
      psychological support to help them to quit smoking. Additionally, offering
      extramural activities and enforcing smoke-free policies in hospital facilities
      will help to reduce patients' access to cigarettes while at the hospital.

PMID- 29221523
TI  - Estimating Effects of Temperature on Dengue Transmission in Colombian Cities.
AB  - BACKGROUND: Dengue fever is a viral disease that affects tropical and subtropical
      regions of the world. It is well known that processes related to virus
      transmission by mosquitoes are highly influenced by weather. Temperature has been
      described as one of the climatic variables that largely governs the development
      and survival of mosquito eggs as well as the survival of all insect stages.
      Previously, we noted that high temperatures in the Colombian city of Riohacha
      negatively affect the establishment of dengue virus (DENV) infection in
      mosquitoes; in Bello and Villavicencio cities, which have lower average
      temperatures, DENV infection rates in mosquitoes are positively associated with a
      gradual increase in temperature. Here, we test the hypothesis that a similar
      effect of temperature can be detected in the incidence in the human population
      inhabiting dengue-endemic cities in Colombia. OBJECTIVE: Our objective was to
      evaluate the effect of climate variables related to temperature on DENV incidence
      in human populations living in DENV-endemic cities in Colombia. METHODS:
      Epidemiologic data from the Instituto Nacional de Salud from 2012-2015 and 7
      variables related to temperature were used to perform Spearman rank sum test
      analyses on 20 Colombian cities. Additionally, locally estimated scatterplot
      smoothing analyses were performed to describe the relationship among temperatures
      and incidence. FINDINGS: Results indicated that Colombian cities with average and
      maximum temperatures greater than 28 degrees C and 32 degrees C, respectively,
      had an inversely related relationship to DENV incidence, which is in accordance
      with areas where higher temperatures are recorded in Colombia. CONCLUSION:
      Climatic variables related to temperature affect dengue epidemiology in different
      way. According to the temperature of each city, transmission might be positively
      or negatively affected.

PMID- 29221524
TI  - Leishmaniasis: Who Uses Personal Protection among Military Personnel in Colombia?
AB  - BACKGROUND: Leishmaniasis is common in Colombia, negatively affecting the health
      of military personnel active in endemic areas. The disease is transmitted by sand
      fly bites. Therefore, during duty, use of long-sleeved uniforms and other clothes
      treated with permethrin and application of mosquito repellent are important
      personal preventive measures. OBJECTIVE: The objective of this study was to
      assess personal and occupational factors associated with the use of personal
      protection in male soldiers deployed to Leishmaniasis-endemic areas. METHODS:
      Three hundred soldiers participated in a cross-sectional questionnaire study
      (response 84.3%). The self-administered questionnaire contained questions about
      sociodemographics, duration of service, compliance with personal mosquito
      protection, and knowledge about leishmaniasis. Descriptive analyses were followed
      by multiple logistic regression models adjusted for potential confounders
      (EpiInfo Version 7.0) FINDINGS: Overall, 23% of the soldiers reported complete
      use of the recommended personal protection measures. About 83% of the
      participants had heard about leishmaniasis. In the adjusted regression model,
      knowledge about leishmaniasis (adjusted odds ratio = 2.9; 95% confidence
      interval: 1.1-7.2) and being enrolled in the army for more than 5 years (2.2; 1.1
      4.1) increased the odds of using personal protection. CONCLUSIONS: Improving
      knowledge about leishmaniasis is one measure to increase use of personal
      protection, thereby diminishing the risk of infection.

PMID- 29221525
TI  - Peer-Reviewed Veterinary Journals From Arabic-Speaking Countries: A Systematic
      Review.
AB  - BACKGROUND: The prevalence of diseases of foodborne and zoonotic origin in Arabic
      speaking countries highlights the importance of collaboration between human and
      animal health professionals. However, accessibility of research and evidence
      based practices in these countries is not well characterized. This brief report
      determines the availability of professional veterinary journals within the Arabic
      speaking region. METHODS: An electronic search using 6 databases assessed for
      publication period, activity status, and available languages incorporated all
      aspects of veterinary medicine and specialties. RESULTS: Among 29 veterinary
      journals identified, the oldest current publication originated 63 years ago, with
      10 journals currently interrupted or ceased. All 19 currently active journals are
      available electronically as open access, with 8 also offered in paper format.
      Veterinary journals published within Arabic-speaking countries are predominantly
      produced in Egypt, Iraq, and Sudan. CONCLUSION: Electronic access is lacking
      compared with English-speaking countries, and there is a lack of journals with an
      Arabic-language option. The reasons associated with language options in
      veterinary publications are not immediately apparent, yet may highlight
      differences among public health, health education, and zoonotic professionals and
      the populations they serve. Veterinary journals in Arabic-speaking countries do
      not adequately represent the overall region and are limited in access. Further
      evaluation of regional culture and publisher preferences is indicated to identify
      new collaboration opportunities among health professionals and local
      stakeholders.

PMID- 29221526
TI  - Children's Environmental Health Indicators for Low- and Middle-Income Countries
      in Asia.
AB  - BACKGROUND: Given that low- and middle-income countries (LMICs) in Asia still
      have high child mortality rates, improved monitoring using children's
      environmental health indicators (CEHI) may help reduce preventable deaths by
      creating healthy environments. OBJECTIVES: Thus, the aim of this study is to
      build a set of targeted CEHI that can be applied in LMICs in Asia through the
      CEHI initiative using a common conceptual framework. METHODS: A systematic review
      was conducted to identify the most frequently used framework for developing CEHI.
      Due to the limited number of eligible records, a hand search of the reference
      lists and an extended search of Google Scholar were also performed. Based on our
      findings, we designed a set of targeted CEHI to address the children's
      environmental health situation in LMICs in Asia. The Delphi method was then
      adopted to assess the relevance, appropriateness, and feasibility of the targeted
      CEHI. FINDINGS: The systematic review indicated that the Driving-Pressure-State
      Exposure-Effect-Action framework and the Multiple-Exposures-Multiple-Effects
      model were the most common conceptual frameworks for developing CEHI. The
      Multiple-Exposures-Multiple-Effects model was adopted, given that its population
      of interest is children and its emphasis on the many-to-many relationship. Our
      review also showed that most of the previous studies covered upper-middle- or
      high-income countries. The Delphi results validated the targeted CEHI. The
      targeted CEHI were further specified by age group, gender, and place of residence
      (urban/rural) to enhance measurability. CONCLUSIONS: Improved monitoring systems
      of children's environmental health using the targeted CEHI may mitigate the data
      gap and enhance the quality of data in LMICs in Asia. Furthermore, critical
      information on the complex interaction between the environment and children's
      health using the CEHI will help establish a regional environmental children's
      health action plan, named "The Children's Environment and Health Action Plan for
      Asia."

PMID- 29221527
TI  - Social Experiences of Women with Obstetric Fistula Seeking Treatment in Kampala,
      Uganda.
AB  - BACKGROUND: Obstetric fistula is a preventable and treatable condition
      predominately affecting women in low-income countries. Understanding the social
      context of obstetric fistula may lead to improved prevention and treatment.
      OBJECTIVES: This study investigated social experiences of women with obstetric
      fistula seeking treatment at Mulago Hospital in Kampala, Uganda. METHODS: A
      descriptive study was conducted among women seeking treatment for obstetric
      fistula during a surgical camp in July 2011 using a structured questionnaire.
      Descriptive statistics were computed regarding sociodemographics, obstetric
      history, and social experience. FINDINGS: Fifty-three women participated; 39
      (73.58%) leaked urine only. Median age was 29 years (range: 17-58), and most were
      married or separated. About half (28, 47.9%) experienced a change in their
      relationship since acquiring obstetric fistula. More than half (27, 50.94%)
      acquired obstetric fistula during their first delivery, despite almost everyone
      (50, 94.3%) receiving antenatal care. The median years suffering from obstetric
      fistula was 1.25. Nearly every participant's social participation changed in at
      least one setting (51, 96.23%). Most women thought that a baby being too big or
      having kicked their bladder was the cause of obstetric fistula. Other
      participants thought health care providers caused the fistula (15, 32.61%; n =
      46), with 8 specifying that the bladder was cut during the operation (cesarean
      section). Knowing someone with obstetric fistula was influential in pursuing
      treatment. The majority of participants planned to return to family (40, 78.43%;
      n = 51) and get pregnant after repair (35, 66.04%; n = 53). CONCLUSION: Study
      participants experienced substantial changes in their social lives as a result of
      obstetric fistula, and there were a variety of beliefs regarding the cause. The
      complex social context is an important component to understanding how to prevent
      and treat obstetric fistula. Further elucidation of these factors may bolster
      current efforts in prevention and holistic treatment.

PMID- 29221528
TI  - Evaluation of Iron Deficiency Anemia in a Pediatric Clinic in the Dominican
      Republic.
AB  - BACKGROUND: Iron deficiency and iron deficiency anemia affect billions of people
      worldwide. Infants and young children are the most vulnerable. The Ninos Primeros
      en Salud pediatric clinic aims to follow the American Academy of Pediatrics (AAP)
      recommendation to screen all children at 12 months of age, a vital period for
      development and the time of greatest risk. OBJECTIVES: To evaluate the clinic's
      performance screening for, diagnosing, and treating iron deficiency anemia; and
      to describe the prevalence and severity of anemia in infants and children
      attending a perirural clinic in the Dominican Republic. METHODS: A total of 293
      charts were reviewed for hemoglobin tests performed between 9 and 15 months of
      age. If a hemoglobin screening was performed, then sociodemographic
      characteristics, medical history, and laboratory data were collected. If blood
      tests revealed anemia, then the presence or absence of documented anemia
      diagnosis as well as the presence or absence of documented provision of iron
      therapy were recorded. FINDINGS: Less than one-third (87, 29.7%) of patients had
      a documented hemoglobin test performed in this age range. Of these, 89.6%
      indicated anemia and nearly half (48.6%) revealed moderate anemia. One-third
      (34%) of hemoglobin results revealing anemia were not accompanied by a documented
      diagnosis. The vast majority (86.5%) of results indicated microcytosis, yet just
      more than half (50.8%) of anemic patients received iron therapy. CONCLUSIONS:
      Many children at the clinic were not screened for iron deficiency anemia during
      the period of highest risk. In the participants screened, iron deficiency anemia
      was underdiagnosed and often untreated. Anemia is a significant burden in this
      community-one demanding reliable screening and universal supplementation.

PMID- 29221529
TI  - The Effect of Early Marriage Timing on Women's and Children's Health in Sub
      Saharan Africa and Southwest Asia.
AB  - BACKGROUND: Age of marriage is a barrier to mother's health care around pregnancy
      and children health outcomes. OBJECTIVE: We provide evidence on the health
      benefits of postponing early marriage among young wives (from age 10-14 to age 15
      17) on women's health care and children's health for sub-Saharan Africa (SSA) and
      Southwest Asia (SWA). METHODS: We use data for 39 countries from the Demographic
      and Health Surveys to estimate the effects of postponing early marriage for
      women's health care and children's health outcomes and immunization using
      matching techniques. We also assess whether women's health empowerment and health
      constraints are additional barriers. FINDINGS: We found that in SSA, delaying the
      age of marriage from age 10-14 to age 15-17 and from age 15-17 to age 18 or older
      leads to an increase in maternal neotetanus vaccinations of 2.4% and 3.2%,
      respectively; gains in the likelihood of postnatal checks are larger for delayed
      marriage among the youngest wives (aged 10-14). In SWA, the number of antenatal
      visits increases by 34% and the likelihood of having a skilled birth attendant
      goes up to 4.1% if young wives postpone marriage. In SSA, the probability of
      children receiving basic vaccinations is twice as large and their neonatal
      mortality reduction is nearly double if their mothers married between ages 15-17
      instead of at ages 10-14. The extent of these benefits is also shaped by supply
      constraints and cultural factors. For instance, we found that weak bargaining
      power on health decisions for young wives leads to 11% fewer antenatal visits
      (SWA) and 13% less chance of attending postnatal checks (SSA). CONCLUSIONS:
      Delaying age of marriage among young wives can lead to considerable gains in
      health care utilization and children health in SSA and SWA if supported by
      policies that lessen supply constraints and raise women's health empowerment.

PMID- 29221530
TI  - Parenting Practices and Associations with Development Delays among Young Children
      in Dominican Republic.
AB  - BACKGROUND: According to the World Health Organization, >200 million children in
      low- and middle-income countries experience developmental delays. However,
      household structure and parenting practices have been minimally explored as
      potential correlates of developmental delay in low- and middle-income countries,
      despite potential as areas for intervention. OBJECTIVE: The objective of the
      study was to examine associations of developmental delays with use of World
      Health Organization-recommended parenting practices among a clinic-based cohort
      of children aged 6-60 months attending in La Romana, Dominican Republic. METHODS:
      This study was conducted among 74 caregiver-child pairs attending the growth
      monitoring clinic at Hospital Francisco Gonzalvo in June 2015. The Malawi
      Developmental Assessment Tool was adapted and performed on each child to assess
      socioadaptive, fine motor, gross motor, and language development. The IMCI
      Household Level Survey Questionnaire was used to assess parenting practices.
      Fisher's exact test was used to determine associations significant at P < .05.
      Significant variables were then entered into a multivariable logistic regression.
      FINDINGS: Almost two-thirds of children had a delay in at least 1 developmental
      domain. Most caregivers used scolding (43.2%) or spanking (44%) for child
      discipline. Children who were disciplined by spanking and scolding were more
      likely to have language delay (P = .007) and socioadaptive delay (P = .077),
      respectively. On regression analysis, children with younger primary caregivers
      had 7 times higher odds of language delay (adjusted odds ratio [AOR]: 7.35, 95%
      confidence interval [CI]: 1.52-35.61) and 4 times greater odds of any delay (AOR:
      4.72, 95% CI: 1.01-22.22). In addition, children punished by spanking had 5 times
      higher odds of having language delay (AOR: 5.04, 95% CI: 1.13-22.39).
      CONCLUSIONS: Parenting practices such as harsh punishment and lack of positive
      parental reinforcement were found to have strong associations with language and
      socioadaptive delays. Likewise, delays were also more common among children with
      younger caregivers.

PMID- 29221531
TI  - Suboptimal Breastfeeding Practices among Women in Rural and Low-Resource
      Settings: a Study of Women in Rural Mysore, India.
AB  - BACKGROUND: Breastfeeding rates are progressively increasing worldwide while
      optimal breastfeeding practices are lagging behind, especially in rural and low
      resource settings like India. OBJECTIVES: This study estimated the prevalence of
      and factors associated with suboptimal breastfeeding practices among mother
      infant dyads in rural southern India. METHODS: This is a cross-sectional analysis
      of data collected in Mysore District from 2008-2011 from 1294 mother-infant
      dyads. All women answered an interviewer-administered survey, which included
      maternal, infant, and sociodemographic information and breastfeeding-related
      characteristics. Logistic regressions were conducted to determine factors
      associated with suboptimal breastfeeding practice. FINDINGS: About 20% (n = 281)
      of mothers reported delayed initiation of breastfeeding. Mothers who were
      unsatisfied with the infant's gender had higher odds of delayed breastfeeding
      (adjusted odds ratio [AOR]: 1.42, 95% confidence interval [CI]: 1.00, 2.00). Odds
      of delayed initiation were significantly lower among mothers who received 7-10
      antenatal checkups (AOR: 0.59, 95% CI: 0.41, 0.87) and assistance during
      breastfeeding (AOR: 0.73, 95% CI: 0.57, 0.95). About half (51.4%) the sample did
      not breastfeed exclusively for the first 6 months. Older age was associated with
      lower odds of nonexclusive breastfeeding (AOR: 0.95, 95% CI: 0.92, 1.00).
      Compared with mothers with no education, mothers with primary education (AOR:
      1.94, 95% CI: 1.35, 2.79) or more than primary education (AOR: 1.58, 95% CI:
      1.10, 2.26) had higher odds of nonexclusive breastfeeding. CONCLUSIONS: Optimal
      breastfeeding practices were influenced by a multitude of factors, including
      maternal age, education, number of antenatal checkups, receiving assistance with
      breastfeeding, and satisfaction with the infant's gender. Health promotion
      efforts should focus on encouraging mothers to attend antenatal care visits.
      Early antenatal education and counseling should include breastfeeding education
      in early antenatal visits. Further research should examine how to mitigate the
      effect of gender preference on initiation of breastfeeding.

PMID- 29221532
TI  - Intentional Exploration on International Service Learning Trips: Three Questions
      for Global Health.

PMID- 29221533
TI  - Global Health Career Interest among Medical and Nursing Students: Survey and
      Analysis.
AB  - BACKGROUND: Global health experiences undertaken in international settings (GHEs)
      are becoming an increasingly prevalent aspect of health professions education
      and, as such, merit comprehensive analysis of the impact they have on students
      and host communities. OBJECTIVE: To assess the associations between
      demographic/experiential factors and the interest of health professions students
      in careers involving global health. METHODS: A cross-sectional survey was
      administered online to a convenience sample of medical and nursing students at
      Johns Hopkins University. Questions addressed level of interest in a global
      health career, prior GHEs, and demographic information. Items were either Likert
      scale or multiple choice. Various regression analyses were performed. FINDINGS:
      Of 510 respondents, 312 (61.2%) expressed interest in a global health career and
      285 (55.9%) had prior GHEs. Multivariate logistic regression found female sex,
      age >=27 years, household income <$100,000/y, and a prior research-related GHE
      independently associated with higher interest in global health careers. On subset
      analysis of participants with one or more prior GHEs: age >=27 years, household
      income <$100,000/y, a prior research-related GHE, and having multiple GHEs were
      each independently associated with increased interest in a global health career.
      CONCLUSIONS: Simply participating in a global health experience abroad is not
      significantly associated with interest in a global health career. However, sex,
      age, household income, and research-related GHEs are significantly associated
      with global health career interest. These findings may inform the development of
      global health programs at medical and nursing schools and can guide efforts to
      increase the number of health care professionals entering global health careers.

PMID- 29221534
TI  - On Becoming a Global Citizen: Transformative Learning Through Global Health
      Experiences.
AB  - BACKGROUND: Globalization has increased the demand for international experiences
      in medical education. International experiences improve medical knowledge,
      clinical skills, and self-development; influence career objectives; and provide
      insights on ethical and societal issues. However, global health rotations can end
      up being no more than tourism if not structured to foster personal transformation
      and global citizenship. OBJECTIVE: We conducted a qualitative assessment of
      trainee-reported critical incidents to more deeply understand the impact of our
      global health experience on trainees. METHODS: A cross-sectional survey was
      administered to trainees who had participated in a 2-month elective in Kenya from
      January 1989 to May 2013. We report the results of a qualitative assessment of
      the critical incident reflections participants (n = 137) entered in response to
      the prompt, "Write about one of your most memorable experiences and explain why
      you chose to describe this particular one." Qualitative analyses were conducted
      using thematic analysis and crystallization immersion analytic methods based on
      the principles of grounded theory, employing a constructivists' research
      paradigm. FINDINGS: Four major themes emerged. These themes were Opening Oneself
      to a Broader World View; Impact of Suffering and Death; Life-Changing
      Experiences; and Commitment to Care for the Medically Underserved. CONCLUSIONS:
      Circumstances that learners encounter in the resource-scarce environment in Kenya
      are eye-opening and life-changing. When exposed to these frame-shifting
      circumstances, students elaborate on or transform existing points of view. These
      emotionally disruptive experiences in an international health setting allowed
      students to enter a transformational learning process with a global mind.
      Students can see the world as an interdependent society and develop the capacity
      to advance both their enlightened self-interest and the interest of people
      elsewhere in the world as they mature as global citizens. Medical schools are
      encouraged to foster these experiences by finding ways to integrate them into
      curriculum.

PMID- 29221535
TI  - Outcomes of Global Public Health Training Program for US Minority Students: A
      Case Report.
AB  - The numbers and success of minority students in science and the health fields
      remain relatively low. This study presents the outcomes of a research training
      program as an illustrative case study. The Short-Term Training Program for
      Minority Students (STPMS) recruits underrepresented minority undergraduate and
      graduate students for immersion in research training. A total of 69 students
      participated in the STPMS between 1995 and 2012, and 59 of these completed our
      survey to determine the perceived impact of the program on the students'
      motivations and professional development. Results indicated that motivations to
      participate in the STPMS were commonly related to long-term professional
      development, such as obtaining mentoring and guidance in career decision making,
      rather than gaining specific research skills or for economic reasons. Students
      reported that participation in short-term research training had the most
      significant effect on improving their attitudes toward biomedical research and
      promoted positive attitudes toward future careers in health research. A total of
      85% of the program's alumni have since completed or are currently working toward
      a degree in higher education, and 79% are currently working in science research
      and health care fields. Overall, the short-term training program improved
      students' attitudes toward research and health science careers. Mentoring and
      career guidance were important in promoting academic development in students.

PMID- 29221536
TI  - Exploration of Global Health Careers Across the Medical Fields.
AB  - BACKGROUND: Despite expansion of interest among American medical students in
      global health (GH), academic medical centers face multiple obstacles to the
      development of structured GH curricula and career guidance. To meet these demands
      we sought to provide a systematic analysis of the accounts of GH experts.
      METHODS: We developed a collaborative, interview-based, qualitative analysis of
      GH experiences across six career-related themes that are relevant to medical
      students interested in GH: justification, medical education, economics, research
      prospects, law and ethics, and work-life balance. Seven GH faculty members were
      interviewed for 30-90 minutes using sample questions as guidelines. We applied a
      grounded theory approach to analyze the interview transcripts to discover an
      emerging theory pertinent to GH trainees. FINDINGS: Regarding justification, 4
      respondents defined GH as work with the underserved irrespective of geographic
      location; 5 respondents found sustainability imperative; and all respondents
      believe GH creates better physicians. Respondents identified many physician
      competencies developed through GH medical education, with 5 respondents agreeing
      that work with underserved populations has transformative potential. Concerning
      economics, 3 respondents acknowledged GH's popularity among trainees, resulting
      in increased training opportunities, and 2 respondents emphasized an associated
      deficiency in program quality. All respondents described career models across
      specialties. Four respondents noted funding challenges when discussing research
      prospects. Within the theme of laws and ethics, 4 respondents perceived
      inadequate accountability, and 6 respondents identified ways to create
      accountability. Finally, 6 respondents recognized family demands can compromise
      one's GH career and thus work-life balance. CONCLUSION: Despite diverse
      perspectives on the meaning and sustainability of GH work, this analysis provides
      a nascent framework that may inform curricular development for GH trainees.
      Suggestions are offered for elaborating this framework to fully exploit the
      transformative potential of GH training in medical education.

PMID- 29221537
TI  - Strengthening Global Health Outreach Programs Through Pharmacy Services.

PMID- 29221538
TI  - Making Online Outbreak Surveillance Work for all.

PMID- 29221539
TI  - Partnership Conference.
AB  - BACKGROUND: The Duke Global Health Institute (DGHI) was founded in 2006 with a
      goal to foster interdisciplinary global health education and research across Duke
      University and Duke Medical Center. Critical to achieving this goal is the need
      to develop and sustain strong international partnerships. OBJECTIVE: To host a
      conference with multiple international partners and strengthen existing
      relationships. METHODS: After a deliberate year-long planning process, DGHI
      convened a Partnership Conference with its international partners on the Duke
      University campus in conjunction with its 10th Anniversary Celebration. The
      Partnership Conference sought to promote an exchange of novel ideas in support of
      global health education and research, explore new collaborations in South-South
      relationships, and identify and facilitate pursuit of new educational and
      research opportunities. FINDINGS: A total of 25 partners from 10 countries and 46
      DGHI faculty members participated in the 3-day event in October 2016. Activities
      included workshops on preselected research topics, educational symposia on novel
      teaching methods and harnessing technological advances, introduction of the
      Health Humanities Laboratory to prepare students and trainees for fieldwork, and
      discussions of research infrastructure and training needs. Surveys from visiting
      partners revealed a high degree of satisfaction. Proposed action items include
      methods to realize improved communications, enhancement of mutual education
      opportunities, support and mentoring to build local research capacity, and more
      exchange of faculty and students between partnering institutions. CONCLUSIONS:
      With careful planning from all parties, a multilateral partnership conference
      including both university and medical center faculty can be a productive forum
      for exchange on global health education and research. Sustaining such
      partnerships is vital to the success of global health scholarship.

PMID- 29221540
TI  - On Essentiality and the World Health Organization's Model List of Essential
      Medicines.
AB  - BACKGROUND: In 1977 the World Health Organization created its first Model List of
      Essential Medicines-a list designed to aid countries in determining which
      medicines to prioritize on their National Essential Medicines Lists. In
      classifying drugs as "essential," the World Health Organization has historically
      stressed drugs' ability to meet priority health needs of populations and cost.
      OBJECTIVES: In this paper we trace the fluctuations in the application of cost
      and priority status of disease as criteria for essential medicines throughout the
      reports published by the WHO Expert Committee on Selection and Use of Essential
      Medicines since 1977. METHODS: We analyzed essential medicines lists published on
      the World Health Organization website since 1977 for trends in criteria
      concerning cost and priority status of disease. Where, available, analyzed the
      World Health Organization Expert Committee analysis rationalizing why certain
      medicines were or were not added and were or were not removed. RESULTS: The
      application of the criteria of cost and priority status of essential medicines
      has fluctuated dramatically over the years. CONCLUSIONS: The definition of
      essential medicines has shifted and now necessitates a new consensus on normative
      definitions and criteria. A more standardized and transparent set of procedures
      for choosing essential medicines is required.

PMID- 29221541
TI  - The Global Health Nursing Imperative: Using Competency-Based Analysis to
      Strengthen Accountability for Population Focused Practice, Education, and
      Research.
AB  - BACKGROUND: The Quad Council Competencies for Public Health Nurses are used to
      guide community and public health nursing course development in baccalaureate
      nursing programs. As clinical practice has expanded to global settings, the
      appropriateness of the 2011 Quad Council Public Health Nursing (PHN) Competencies
      to guide global clinical practice and evaluation was questioned. OBJECTIVE: To
      describe a comparison and analysis of three sets of competencies: PHN
      competencies, competencies for global health nurses, and interprofessional
      competencies for health professionals. METHOD: A literature review identified the
      most current guidelines and competencies for global health practice. Two seminal
      articles, "Global Health Competencies for Nurses in the Americas" and
      "Identifying Interprofessional Global Health Competencies for 21st-Century Health
      Professionals," were reviewed and compared with the 2011 Quad Council Public
      Health Nursing Competencies. A six-member multi-site team conducted a qualitative
      thematic approach to competency analysis. A four column crosswalk spreadsheet
      grid was used for comparison of the three sets of competencies. Column four was
      created to identify possible exemplars for clinical practice. FINDINGS: Gaps
      exist in the PHN competencies for specific global and interprofessional
      competencies. RECOMMENDATIONS: Enhanced and consistent emphasis on
      population/global health, and interprofessional content throughout nursing
      curricula is necessary to prepare providers for practice in global settings.
      Incorporation of global and interprofessional competencies should be considered
      in the revision of competencies for PHN practice to enhance productive
      contributions to community health outcomes. Consideration of proper placement of
      content gaps within basic and advanced nursing education as well as leveling for
      community/public health nursing practice needs to be addressed by nursing
      education and practice. In the interim, a special course or elective may be
      appropriate, especially for schools having clinical nursing practicums in
      international settings. Clinical evaluation in low-resource settings needs to be
      enhanced and aligned with competencies.

PMID- 29221542
TI  - Ability to Pay for Future National Health Financing Scheme among Malaysian
      Households.
AB  - BACKGROUND: Malaysia is no exception to the challenging health care financing
      phenomenon of globalization. OBJECTIVES: The objective of the present study was
      to assess the ability to pay among Malaysian households as preparation for a
      future national health financing scheme. METHODS: This was a cross-sectional
      study involving representative samples of 774 households in Peninsular Malaysia.
      FINDINGS: A majority of households were found to have the ability to pay for
      their health care. Household expenditure on health care per month was between
      MYR1 and MYR2000 with a mean (standard deviation [SD]) of 73.54 (142.66), or in a
      percentage of per-month income between 0.05% and 50% with mean (SD) 2.74 (5.20).
      The final analysis indicated that ability to pay was significantly higher among
      younger and higher-income households. CONCLUSIONS: Sociodemographic and
      socioeconomic statuses are important eligibility factors to be considered in
      planning the proposed national health care financing scheme to shield the needed
      group from catastrophic health expenditures.

PMID- 29221543
TI  - Community Health Workers in Diabetes Prevention and Management in Developing
      Countries.
AB  - BACKGROUND: There is limited evidence regarding the effect of community health
      worker (CHW) interventions for prevention and management of the burgeoning
      epidemic of noncommunicable diseases (NCDs) in low- and middle-income countries
      (LMICs). The objective of this review was to critically appraise evidence
      regarding the effectiveness of CHW interventions for prevention and management of
      type 2 diabetes mellitus (T2DM) in LMICs. METHODS: To identify studies that
      reported the effect of CHW interventions for prevention and management of T2DM in
      LMICs, Medline/PubMed, EMBASE, Web of Science (Science and Social Science
      Citation Indices), EBSCO (PsycINFO and CINAHL), POPLINE, the Cochrane Metabolic
      and Endocrine Disorders Group's Specialized Register, the Cochrane Central
      Register of Controlled Trials, the Grey literature (Google, Google Scholar), and
      reference lists of identified articles were searched from inception to May 31,
      2017. FINDINGS: Ten studies were included (4 pre- and post-studies, 2 randomized
      controlled trials, 2 cohort studies, 1 cross-sectional study, and 1 case-control
      study). The role of CHWs consisted of patient education, identification and
      referral of high-risk individuals to physicians, and provision of social support
      through home visits. Positive outcomes were reported in 7 of 10 studies. These
      outcomes included increased knowledge of T2DM symptoms and prevention measures;
      increased adoption of treatment-seeking and prevention measures; increased
      medication adherence; and improved fasting blood sugar, glycated hemoglobin, and
      body mass index. Three studies showed no significant outcomes. CONCLUSIONS: CHWs
      have the potential to improve knowledge, health behavior, and health outcomes
      related to prevention and management of T2DM in LMICs. Given the limited number
      of studies included in this review, robust conclusions cannot be drawn at the
      present time.

PMID- 29221544
TI  - Big Data Knowledge in Global Health Education.
AB  - The ability to synthesize and analyze massive amounts of data is critical to the
      success of organizations, including those that involve global health. As
      countries become highly interconnected, increasing the risk for pandemics and
      outbreaks, the demand for big data is likely to increase. This requires a global
      health workforce that is trained in the effective use of big data. To assess
      implementation of big data training in global health, we conducted a pilot survey
      of members of the Consortium of Universities of Global Health. More than half the
      respondents did not have a big data training program at their institution.
      Additionally, the majority agreed that big data training programs will improve
      global health deliverables, among other favorable outcomes. Given the observed
      gap and benefits, global health educators may consider investing in big data
      training for students seeking a career in global health.

PMID- 29221546
TI  - Commentary on Global Health in Malawi: A Collection of Poems, by Zachary G.
      Jacobs, M.D.

PMID- 29221545
TI  - #Globalhealth Twitter Conversations on #Malaria, #HIV, #TB, #NCDS, and #NTDS: a
      Cross-Sectional Analysis.
AB  - BACKGROUND: Advocates use the hashtag #GlobalHealth on Twitter to draw users'
      attention to prominent themes on global health, to harness their support, and to
      advocate for change. OBJECTIVES: We aimed to describe #GlobalHealth tweets
      pertinent to given major health issues. METHODS: Tweets containing the hashtag
      #GlobalHealth (N = 157,951) from January 1, 2014, to April 30, 2015, were
      purchased from GNIP Inc. We extracted 5 subcorpora of tweets, each with 1 of 5 co
      occurring disease-specific hashtags (#Malaria, #HIV, #TB, #NCDS, and #NTDS) for
      further analysis. Unsupervised machine learning was applied to each subcorpus to
      categorize the tweets by their underlying topics and obtain the representative
      tweets of each topic. The topics were grouped into 1 of 4 themes (advocacy;
      epidemiological information; prevention, control, and treatment; societal impact)
      or miscellaneous. Manual categorization of most frequent users was performed.
      Time zones of users were analyzed. FINDINGS: In the entire #GlobalHealth corpus
      (N = 157,951), there were 40,266 unique users, 85,168 retweets, and 13,107 unique
      co-occurring hashtags. Of the 13,087 tweets across the 5 subcorpora with co
      occurring hashtag #malaria (n = 3640), #HIV (n = 3557), #NCDS (noncommunicable
      diseases; n = 2373), #TB (tuberculosis; n = 1781), and #NTDS (neglected tropical
      diseases; n = 1736), the most prevalent theme was prevention, control, and
      treatment (4339, 33.16%), followed by advocacy (3706, 28.32%), epidemiological
      information (1803, 13.78%), and societal impact (1617, 12.36%). Among the top 10
      users who tweeted the highest number of tweets in the #GlobalHealth corpus, 5
      were individual professionals, 3 were news media, and 2 were organizations
      advocating for global health. The most common users' time zone was Eastern Time
      (United States and Canada). CONCLUSIONS: This study highlighted the specific
      #GlobalHealth Twitter conversations pertinent to malaria, HIV, tuberculosis,
      noncommunicable diseases, and neglected tropical diseases. These conversations
      reflect the priorities of advocates, funders, policymakers, and practitioners of
      global health on these high-burden diseases as they presented their views and
      information on Twitter to their followers.

PMID- 29221547
TI  - Quality of Care.

PMID- 29221548
TI  - ?

PMID- 29221549
TI  - [Hypnosis to fight against pain and anxiety in palliative care].
AB  - In our society, hypnosis sometimes has a negative, distorted image. For several
      years now it has become more widespread in the healthcare field and its use has
      increased in caring for symptoms such as pain and anxiety. It can be of great
      help in palliative situations.

PMID- 29221550
TI  - [Assessment of professional practices in treating cardiac arrest].
AB  - An assessment of professional practices was carried out in 2013-2014 with the aim
      of improving the treatment of cardiac arrest in hospitals. Two methods were used:
      an assessment by questionnaire to evaluate theoretical knowledge and a practical
      assessment of external cardiac massage. The results highlight the need for
      greater knowledge. The use of cardiac massage must be included in continuing
      professional development.

PMID- 29221551
TI  - [Reflections on prehospitalisation deaths].
AB  - In the past, death was a family and community affair, but today it is
      institutional and entrusted to healthcare personnel. Thanks to a questionnaire on
      their feelings about prehospitalisation deaths, the experience and training needs
      for healthcare personnel at a mobile emergency and intensive care service were
      analysed. The majority of these professionals had been confronted with
      difficulties when faced with prehospitalisation deaths. There is little
      understanding of religious rites, even though this is an important point in
      dealing with the situation. There is a strong desire for training. The
      pedagogical support offered in response to the needs expressed was recognised as
      being useful and should be more widespread.

PMID- 29221552
TI  - ?

PMID- 29221553
TI  - [Healthcare commitment, a necessity today].
AB  - Healthcare commitment is a mosaic of attention to and encounters with the Other,
      with brotherhood and effectiveness. It means knowing the rules, but not
      submitting to norms. It is a responsibility that comes from the feeling of one's
      own vulnerability as much as it is a question of sharing the values of the sick
      person with other healthcare personnel.

PMID- 29221554
TI  - [Psychological commitment: adaptive functions, paradoxes, modalities and
      components].
AB  - The process of psychological commitment, its adaptive functions and some of the
      difficulties that go along with it are specific. A description of the multimodal
      model of commitment provides an illustration of how motivational, affective,
      cognitive and behavioural mechanisms can be combined. These lead to different
      ways of entering into the commitment, with differing consequences on how the
      individual functions.

PMID- 29221555
TI  - [Is it possible to live without commitment?]
AB  - Commitment is an ethic of life, the condition that ensures one's responsibility
      as a human being. It is the only way to remain free and dignified. Life without
      commitment means just being a bystander, being submissive or giving in to chaos.

PMID- 29221556
TI  - [Associative commitments].
AB  - Volunteering to serve the general interest, that is the profession of faith
      behind associative commitments. Notably, actions by associations undertaken in
      favour of organ donation today must, in their content and forms, reconcile
      tradition and modernity. But they keep their driving principles and values
      intact.

PMID- 29221557
TI  - [Citizen commitment for humanistic values].
AB  - Nowadays, as part of the population is seeking meaning, there are reasons to hope
      that we can live together better in our country. Avoiding resignation and
      passivity, the purpose of developing humanistic values, those of the Republic, is
      to build a society that is fairer, more serene and fraternal. A citizen
      commitment opens up possibilities for this.

PMID- 29221558
TI  - [Firefighter nurse, a twofold commitment].
AB  - Why would anyone want to become a firefighter nurse? This obviously twofold
      commitment is usually the result of an individual and family history, although
      other factors are also at work. The need to serve is reinforced by the
      professional's social audience, the particular features of emergencies, the
      independence, the hierarchy and the positive emotions associated with this
      profession.

PMID- 29221559
TI  - [Choosing to become a nurse, a commitment].
AB  - It appears that, to survive, all people need a commitment, whatever their
      motivations, their degree of involvement and the time they can dedicate to it.
      What does "commitment" really mean to nursing students?

PMID- 29221560
TI  - [Commitment at the heart of the nursing profession].
AB  - Although it is a free choice and appears paradoxical, the choice to be a nurse is
      binding. In keeping with its Code of Ethics, the nursing profession demands an
      ethical, social, political and collective commitment that we cannot shy away from
      or we will fail to fulfil our obligations.

PMID- 29221561
TI  - [Humanitarian nurse, the strength of commitment].
AB  - Every year, hundreds of volunteers leave their home, for few weeks or months, to
      provide humanitarian aid across the world. Joining a humanitarian mission, far
      from being a simple exotic adventure, requires, specially, a strong professional
      skills and personal abilities, maturely and thoughtful motivations. The work of
      humanitarian nurse is first and foremost a full-blown profession.

PMID- 29221563
TI  - ?

PMID- 29221562
TI  - [The caregiver's commitment and its limits].
AB  - The question of commitment and its limits can be envisaged from the point of view
      of supervision in healthcare institutions or in home hospital care. When the
      commitment appears to be frustrated in the healthcare relationship, it must be
      supported and its limits should be defined.

PMID- 29221565
TI  - Hormones in milk.

PMID- 29221564
TI  - ?

PMID- 29221566
TI  - Physiology of milk secretion.
AB  - Milk is a unique and complete nutritive source for the mammal neonate, also
      providing immune protection and developmental signals. Lactation is a complex
      process, proper to the mother and child dyad, and including numerous variables
      ranging from psychological aspects to the secretory functioning of the mammary
      epithelial cells, all contributing to a successful breastfeeding. This review
      gives an integrated overview of the physiology of lactation with a particular
      focus on cellular and molecular mechanisms involved in milk product secretion and
      their regulations.

PMID- 29221567
TI  - Iodine in dairy milk: Sources, concentrations and importance to human health.
AB  - Milk and dairy products are major iodine sources in industrialized countries.
      However, consumption of milk and dairy, as well as their iodine concentrations,
      vary widely, making them an unpredictable iodine source. Milk iodine
      concentrations in industrialized countries range from 33 to 534 MUg/L and are
      influenced by the iodine intake of dairy cows, goitrogen intake, milk yield,
      season, teat dipping with iodine-containing disinfectants, type of farming and
      processing. We estimate milk and dairy contribute ~13-64% of the recommended
      daily iodine intake based on country-specific food intake data. To ensure
      adequate iodine levels but avoid the risk of iodine excess through milk and
      dairy, it is crucial to reduce the wide variations in milk iodine. If iodine
      intakes from iodized salt fall because of public health efforts to reduce salt
      intake, milk and dairy products may become increasingly important sources of
      dietary iodine in the future.

PMID- 29221568
TI  - Nutritional programming by glucocorticoids in breast milk: Targets, mechanisms
      and possible implications.
AB  - Vertical transmission of glucocorticoids via breast milk might pose a mechanism
      through which lactating women could prepare their infants for the postnatal
      environment. The primary source of breast-milk glucocorticoids is probably the
      systemic circulation. Research from our group showed that milk cortisol and
      cortisone concentrations follow the diurnal rhythm of maternal hypothalamus
      pituitary-adrenal axis activity, with a higher abundance of cortisone compared to
      cortisol. Measurement of breast-milk glucocorticoid concentrations is challenging
      due to possible cross-reactivity with progestagens and sex steroids, which are
      severely elevated during pregnancy and after parturition. This requires precise
      methods that are not hindered by cross reactivity, such as LC-MS/MS. There are
      some data suggesting that breast-milk glucocorticoids could promote intestinal
      maturation, either locally or after absorption into the systemic circulation.
      Breast-milk glucocorticoids might also have an effect on the intestinal
      microbiome, although this has not been studied thus far. Findings from studies
      investigating the systemic effects of breast-milk glucocorticoids are difficult
      to interpret, since none took the diurnal rhythm of glucocorticoids in breast
      milk into consideration, and various analytical methods were used. Nevertheless,
      glucocorticoids in breast milk might offer a novel potential pathway for signal
      transmission from mothers to their infants.

PMID- 29221569
TI  - Functional analysis of the IGF-system in milk.
AB  - The development of milk during evolution is considered a more recent step to
      provide the neonate with adequate amounts of energy, nutrients, and specific
      hormonal signals thereby, granting a fast and efficient rate of postnatal growth
      and development. Since the insulin- or the insulin-like growth factor (IGF)
      systems were evolved much earlier, it can be assumed that the functionality of
      the IGF-system has been integrated into the novel matrix milk containing casein
      and whey proteins from the beginnings. In fact, IGFs and IGF-binding proteins
      (IGFBPs) are abundantly present in milk, which is particularly true for fore-milk
      or colostrum and the potential effects of milk-borne IGF-compounds on the
      consuming organisms have in fact been addressed by several studies. Those studies
      examined, if orally administered IGFs can be absorbed by the consumer's gastro
      intestinal tract and thus contribute e.g. to the somatic growth of infants. A
      second line of studies assessed local effects of milk-borne IGFs on growth and
      development of the gastro-intestinal tract itself. Finally, distinct functions of
      isolated IGF-compounds for growth and involution of the mammary gland have also
      been provided in the past. While the consumption of milk seems not to represent a
      major source of endogenous IGFs, accumulating evidence indicates secondary
      effects of milk on the endogenous IGF-system, which may be mediated by
      micronutrients such as branched amino acids and metabolic programming. By
      contrast, direct effects on growth and development of oesophageal and intestinal
      cells have been observed if IGFs were administered orally.

PMID- 29221570
TI  - Neohormones in milk.
AB  - Neohormone systems evolved specifically to regulate those mammalian traits, such
      as internal fertilization, pregnancy and lactation, which have proved to be
      central to the success, environmental independence, and adaptability of mammals
      as a vertebrate group. Neohormones such as oxytocin or relaxin are not only
      involved in the regulation of mammary gland development and function, but are
      also significant components of milk itself. Particularly for the latter hormone,
      it has been shown for the pig that relaxin in the first milk is taken up by the
      gastrointestinal tract of the offspring, enters the neonatal circulation and can
      have specific physiological and epigenetic effects on target organs such as the
      female reproductive system. Nevertheless, there are large gaps in our knowledge
      and understanding of such lactocrine systems especially in regard to other
      neohormones, species, and neonatal organ systems.

PMID- 29221571
TI  - MicroRNAs: Milk's epigenetic regulators.
AB  - Our perception of milk has changed from a "simple food" to a highly sophisticated
      maternal-neonatal nutrient and communication system orchestrating early
      programming of the infant. Milk miRNAs delivered by exosomes and milk fat
      globules derived from mammary gland epithelial cells play a key role in this
      process. Exosomes resist the harsh intestinal environment, are taken up by
      intestinal cells via endocytosis, and reach the systemic circulation of the milk
      recipient. The most abundant miRNA found in exosomes and milk fat globules of
      human and cow's milk, miRNA-148a, attenuates the expression of DNA
      methyltransferase 1, which is critically involved in epigenetic regulation.
      Another important miRNA of milk, miRNA-125b, targets p53, the guardian of the
      genome, and its diverse transcriptional network. The deficiency of exosomal
      miRNAs in infant formula and the persistent uptake of milk miRNAs after the
      nursing period via consumption of cow's milk are two epigenetic aberrations that
      may induce adverse long-term effects on human health.

PMID- 29221572
TI  - Misuse of semantics and basic statistical terms in original articles.

PMID- 29221573
TI  - Editorial overview: Muscle and bone are highly effective communicators.

PMID- 29221574
TI  - Editorial overview: Respiratory: Transformational therapies for cystic fibrosis.

PMID- 29221575
TI  - Clinical outcomes of suprascapular nerve decompression: a systematic review.
AB  - BACKGROUND: Suprascapular neuropathy is an uncommon clinical diagnosis. Although
      there have been a number of case series reporting on this pathologic process, to
      date there has been no systematic review of these studies. This study aimed to
      synthesize the literature on suprascapular neuropathy with regard to clinical
      outcomes. The secondary objective was to detail the diagnosis and treatment of
      suprascapular neuropathy and any associated complications. METHODS: A systematic
      review was performed to identify studies that reported the results or clinical
      outcomes of suprascapular nerve decompression. The searches were performed using
      MEDLINE through PubMed and Cochrane Database of Systematic Reviews. RESULTS:
      Twenty-one studies comprising 275 patients and 276 shoulders met inclusion
      criteria. The mean age was 41.9 years, and mean follow-up was 32.5 months. The
      most common symptom was deep, posterior shoulder pain (97.8%), with a mean
      duration of symptoms before decompression of 19.0 months; 94% of patients
      underwent electrodiagnostic testing before decompression, and 85% of patients had
      results consistent with suprascapular neuropathy. The most common outcome
      reported was the visual analog scale score, followed by the Constant-Murley
      score. The mean postoperative Constant-Murley score obtained was 89% of ideal
      maximum. Ninety-two percent of athletes were able to return to sport. Only 2
      (0.74%) complications were reported in the included studies. CONCLUSIONS:
      Surgical decompression in the setting of suprascapular neuropathy leads to
      satisfactory outcomes as evidenced by the patient-reported outcomes and return to
      sport rate. Furthermore, the rate of complications appears to be low.

PMID- 29221576
TI  - An important lesson in assessing neurovascular involvement in proximal humeral
      fractures: the presence of neuropathic pain in a dysvascular limb.

PMID- 29221577
TI  - Letter to the Editor regarding Trikha et al: "Retrospective analysis of proximal
      humeral fracture-dislocations managed with locked plates".

PMID- 29221578
TI  - Response to Chouhan DK, regarding: "Retrospective analysis of proximal humeral
      fracture-dislocations managed with locked plates".

PMID- 29221580
TI  - Mechanisms of allergen immunotherapy for inhaled allergens and predictive
      biomarkers.
AB  - Allergen immunotherapy is effective in patients with IgE-dependent allergic
      rhinitis and asthma. When immunotherapy is given continuously for 3 years, there
      is persistent clinical benefit for several years after its discontinuation. This
      disease-modifying effect is both antigen-specific and antigen-driven. Clinical
      improvement is accompanied by decreases in numbers of effector cells in target
      organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid
      cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies
      that can inhibit IgE-dependent activation mediated through both high-affinity IgE
      receptors (FcepsilonRI) on mast cells and basophils and low-affinity IgE
      receptors (FcepsilonRII) on B cells. Suppression of TH2 immunity can occur as a
      consequence of either deletion or anergy of antigen-specific T cells; induction
      of antigen-specific regulatory T cells; or immune deviation in favor of TH1
      responses. It is not clear whether the altered long-term memory resides within
      the T-cell or the B-cell compartment. Recent data highlight the role of IL-10
      producing regulatory B cells and "protective" antibodies that likely contribute
      to long-term tolerance. Understanding mechanisms underlying induction and
      persistence of tolerance should identify predictive biomarkers of clinical
      response and discover novel and more effective strategies for immunotherapy.

PMID- 29221581
TI  - Biomarkers for severe eosinophilic asthma.
AB  - The last decade has seen the approval of several new biologics for the treatment
      of severe asthma-targeting specific endotypes and phenotypes. This review will
      examine how evidence generated from the mepolizumab clinical development program
      showed that blood eosinophil counts, rather than sputum or tissue eosinophil
      counts, evolved as a pharmacodynamic and predictive biomarker for the efficacy of
      treatment with mepolizumab in patients with severe eosinophilic asthma. Based on
      the available evidence and combined with clinical judgement, a baseline blood
      eosinophil threshold of 150 cells/MUL or greater or a historical blood eosinophil
      threshold of 300 cells/MUL or greater will allow selection of patients with
      severe eosinophilic asthma who are most likely to achieve clinically significant
      reductions in the rate of exacerbations with mepolizumab treatment.

PMID- 29221583
TI  - Correction.

PMID- 29221584
TI  - ?

PMID- 29221579
TI  - Biomarkers in connective tissue diseases.
AB  - Autoimmune connective tissue diseases are clinically variable, making biomarkers
      desirable for assessing future disease risk, supporting early and accurate
      diagnosis, monitoring disease activity and progression, selecting therapeutics,
      and assessing treatment response. Because of their correlations with specific
      clinical characteristics and often with disease progression, autoantibodies and
      other soluble mediators are considered potential biomarkers. Additional
      biomarkers might reflect downstream pathologic processes or appear because of
      ongoing inflammation and damage. Because of overlap between diseases, some
      biomarkers have limited specificity for a single autoimmune connective tissue
      disease. This review describes select current biomarkers that aid in the
      diagnosis and treatment of several major systemic autoimmune connective tissue
      disorders: systemic lupus erythematosus, rheumatoid arthritis, systemic
      sclerosis, and anti-neutrophil cytoplasmic antibody-associated vasculitides.
      Newly proposed biomarkers that target various stages in disease onset or
      progression are also discussed. Newer approaches to overcome the diversity
      observed in patients with these diseases and to facilitate personalized disease
      monitoring and treatment are also addressed.

PMID- 29221585
TI  - ?
AB  - Atopic dermatitis is a multifactorial disease due to a combination of genetic and
      environmental factors. The pathophysiological mechanisms involved in AD are
      multiple: innate functional abnormality in the skin barrier partly linked to
      mutations of the filaggrin, a major structural protein of the skin; and genes
      involved in innate and adaptive immunity; Finally, the model of the hygiene
      theory has been clarified in recent years: environmental factors alter the
      diversity of skin and digestive microbiomes, and this diversity seems to play a
      major role in the development of atopy.

PMID- 29221586
TI  - ?
AB  - Atopic dermatitis has been described under many names before the XXth century,
      and first illustrated in the early XIXth century. This article presents
      historical images from the first volumes of Robert Willan to the Pratique
      dermatologique, the first encyclopedy published in 1900. Many accurate clinical
      descriptions of the disease can be found in the early treaties of dermatology,
      including the one published by Thomas Carrere in 1740. Since then, Alibert and
      Rayer in France, Hebra and Neumann in Vienna and Duhring and Fox in the USA
      illustrated their atlases with spectacular images of adults or children suffering
      from AD, or from other diseases that might have been considered as eczema
      infantile. Color engravings, color lithographs and black and white photographs
      showed with an increasing precision the semiology of AD, in the context of
      artistic representations of high quality, that have not been surpassed by modern
      photographs. At the beginning of the XXth century the clinical presentation, the
      course and heredity of the disease were perfectly established, introducing a new
      era of research in physiopathology and treatment in the following decades.

PMID- 29221587
TI  - ?
AB  - Avene thermal spring water is recognized for more than two centuries for its
      benefits on skin diseases. Since 1975, the Pierre Fabre Group has modernized the
      facilities, and developed the brand " Eau Thermal Avene ", allowing more than
      2,500 patients/year to be treated by this therapeutic water. The regulation
      requires high standards on origin, bacteriological purity and physico-chemical
      stability. Many works have allowed us to understand its origin, its underground
      path and identify its specific physico-chemical profile. Finally, thanks to its
      therapeutic properties verified in various clinical studies, the " Eau Thermal
      Avene " is the first active ingredient of a variety of products for sensitive
      skin.

PMID- 29221588
TI  - ?
AB  - Atopic dermatitis (AD) is the most frequent disease treated at the Avene
      hydrotherapy center. Children represent a large part of the population due to the
      high prevalence of AD in early childhood. Avene thermal spring water (ATSW) has
      been known for its therapeutic effects since the middle of the 18th century. It
      has been greatly studied over the last decades, with a comprehensive fundamental,
      pharmaco-clinical and clinical approach. Cohort studies using the Scoring Atopic
      Dermatitis (SCORAD) clinical score and the Dermatology Life Quality Index (DLQI)
      or the Children's Dermatology Life Quality Index [CDLQI]) quality of life scores,
      allowed to confirm the clinical results obtained from the previous studies. These
      results were corroborated by clinical trials conducted in atopic patients outside
      the Avene hydrotherapy center, allowing to demonstrate the specific effect of the
      ATSW. Pharmacological and pharmaco-clinical studies evidenced several effects
      that could explain the healing effect of ATSW: effect on histamine release, anti
      inflammatory effects on standardized models, immuno-modulation of some cytokines
      involved in DA physiopathology (interferon [INF], interleukin 2 and 4 [IL-2, IL
      4]), improvement of keratinocyte differentiation, effect on the skin microbioma
      by promoting the development of a diversified non-pathogenic flora. In addition,
      an original microorganism, Aquaphilus dolomiae, never described in another
      medium, has very recently been identified in the ATSW. Aquaphilus dolomiae is
      responsible for significant pharmacological activities on inflammation, pruritus
      and enhancement of innate immunity. This set of works confirms the medical
      significance of the hydrotherapy which should be considered as a complementary
      care in the sometimes difficult management of AD.

PMID- 29221589
TI  - ?
AB  - Human hosts a large number of microorganisms that constitute its microbiome and
      the vast majority of them are very useful and even essentials. The human
      microbiome is a complex ecosystem where live populations of transient or resident
      microorganisms. The process of co-development or co-adaptation played a major
      role in the establishment of indigenous communities and help explain the
      dominance of positive interactions (commensal, symbiotic or mutualistic) in the
      human-microorganism relationship. The assimilation of nutrients, production of
      anti-inflammatory compounds, defense against pathogens, vitamin production or
      stimulating the immune system are some of the key benefits of the indigenous
      microorganisms. Understanding the skin microbiome opens new exploratory fields
      and represents a real challenge for both the academic knowledge and the
      development of new therapeutic approaches.

PMID- 29221590
TI  - ?
AB  - Atopic dermatitis (AD) is an inflammatory and pruritic dermatosis of
      multifactorial origin. Topical steroids are the first line treatment for severe
      AD however alternatives treatment are increasingly needed. A biological
      concentrate was elaborated from culture of an Avene aquatic microflora isolate
      namely Aquaphilus dolomiae. Numerous extracts were evaluated in relevant AD in
      vitro models with human keratinocytes. Among these extracts, a particular one I
      modulia(r) was found to be remarkable in terms of pharmacological activities:
      innate immunity modulating by agonizing Toll like receptor (TLR)2, TLR4 and TLR5,
      induction of anti-microbial peptides, inhibition of cytokines characteristics of
      T helper (Th)1, Th2 and Th17 responses, inhibition of Protease-activated-receptor
      (PAR) 2 and Thymic-stromal-lymphopoeitin (TSLP) both being known to be
      upregulated in pruritus. Additionally, when human dendritic cells (DC) were
      stimulated in vitro by Staphylococcus aureus secretomes from AD children lesions,
      I-modulia(r) was capable to induce IL-10 secretion to activate regular T
      lymphocytes and rendered DC tolerogenic. I-modulia(r), extract of biotech origin
      incorporated in emollient, displays anti-inflammatory, anti-pruritus activities,
      restores homeostasis immune and ameliorates AD in young infant.

PMID- 29221591
TI  - Eradicating BVD, reviewing Irish programme data and model predictions to support
      prospective decision making.
AB  - Bovine Viral Diarrhoea is an infectious production disease of major importance in
      many cattle sectors of the world. The infection is predominantly transmitted by
      animal contact. Postnatal infections are transient, leading to immunologically
      protected cattle. However, for a certain window of pregnancy, in utero infection
      of the foetus results in persistently infected (PI) calves being the major risk
      of BVD spread, but also an efficient target for controlling the infection. There
      are two acknowledged strategies to identify PI animals for removal: tissue tag
      testing (direct; also known as the Swiss model) and serological screening
      (indirect by interpreting the serological status of the herd; the Scandinavian
      model). Both strategies are effective in reducing PI prevalence and herd
      incidence. During the first four years of the Irish national BVD eradication
      programme (2013-16), it has been mandatory for all newborn calves to be tested
      using tissue tag testing. During this period, PI incidence has substantially
      declined. In recent times, there has been interest among stakeholders in a change
      to an indirect testing strategy, with potential benefit to the overall programme,
      particularly with respect to cost to farmers. Advice was sought on the usefulness
      of implementing the necessary changes. Here we review available data from the
      national eradication programme and strategy performance predictions from an
      expert system model to quantify expected benefits of the strategy change from
      strategic, budgetary and implementation points of view. Key findings from our
      work include (i) drawbacks associated with changes to programme implementation,
      in particular the loss of epidemiological information to allow real-time
      monitoring of eradication progress or to reliably predict time to eradication,
      (ii) the fact that only 25% of the herds in the Irish cattle sector (14% beef,
      78% dairy herds) would benefit financially from a change to serosurveillance,
      with half of these participants benefiting by less than EUR 75 per annum at herd
      level or an average of EUR 1.22 per cow, and (iii) opportunities to enhance the
      effectiveness of the current programme, particularly in terms of time to
      eradication, through enforced compliance with PI removal as currently outlined in
      programme recommendations. The assembled information provides scientific
      arguments, contributing to an informed debate of the pros and cons of a change in
      eradication strategy in Ireland.

PMID- 29221592
TI  - Ecosystem features determine seagrass community response to sea otter foraging.
AB  - Comparing sea otter recovery in California (CA) and British Columbia (BC) reveals
      key ecosystem properties that shape top-down effects in seagrass communities. We
      review potential ecosystem drivers of sea otter foraging in CA and BC seagrass
      beds, including the role of coastline complexity and environmental stress on sea
      otter effects. In BC, we find greater species richness across seagrass trophic
      assemblages. Furthermore, Cancer spp. crabs, an important link in the seagrass
      trophic cascade observed in CA, are less common. Additionally, the more recent
      reintroduction of sea otters, more complex coastline, and reduced environmental
      stress in BC seagrass habitats supports the hypotheses that sea otter foraging
      pressure is currently reduced there. In order to manage the ecosystem features
      that lead to regional differences in top predator effects in seagrass
      communities, we review our findings, their spatial and temporal constraints, and
      present a social-ecological framework for future research.

PMID- 29221593
TI  - Individuals at risk of rheumatoid arthritis - The evolving story.

PMID- 29221594
TI  - Periodontal disease and periodontal bacteria as triggers for rheumatoid
      arthritis.
AB  - There is an epidemiological association between periodontitis and rheumatoid
      arthritis (RA), which is hypothesised to lead to enhanced generation of RA
      related autoantibodies that can be detected years before the onset of RA
      symptoms. Periodontitis is a common dysbiotic disease; tissue damage occurs
      because the immune system fails to limit both the resident microbial community
      and the associated local immune response. Certain periodontal bacteria, including
      Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, may
      contribute to RA autoantibody production through direct post-translational
      modification of proteins or, indirectly, by influencing neutrophil-mediated neo
      epitope generation. Oral bacteria that invade the blood may also contribute to
      chronic inflammatory responses and generation of autoantibodies. The putative
      association between periodontitis and the development of RA raises the potential
      of finding novel predictive markers of disease and disease progression and for
      periodontitis treatment to be included in the future as an adjunct to
      conventional RA immunotherapy or as part of a preventive strategy.

PMID- 29221596
TI  - Role of the lung in individuals at risk of rheumatoid arthritis.
AB  - Antibody-positive (seropositive) rheumatoid arthritis (RA) is a complex
      multiphasic disease developing in genetically susceptible individuals following
      environmental challenges (such as smoking). RA-associated autoantibodies can
      develop several years before any clinical signs of joint inflammation, suggesting
      that triggering of this autoimmunity occurs outside the joints. Epidemiological,
      clinical, and molecular studies in seropositive individuals at risk for
      developing RA as well as in early untreated RA suggest a potential role for
      mucosal sites (especially lung mucosa) as RA-associated autoimmunity trigger
      sites. This chapter summarizes clinical and molecular studies supporting the lung
      as a central site for autoimmunity initiation in RA.

PMID- 29221597
TI  - Evolution of autoantibody responses in individuals at risk of rheumatoid
      arthritis.
AB  - Autoantibodies such as rheumatoid factors (RFs), anti-citrullinated protein
      antibodies (ACPAs), and other anti-modified protein antibodies are important risk
      factors for the development of rheumatoid arthritis (RA) and probably play an
      important role in its pathogenesis. In the phase before clinical arthritis
      becomes apparent, different autoantibody responses can evolve because of
      increases in their level, isotype switching, affinity maturation, epitope
      spreading, and a changing glycosylation profile. This evolution may be crucial
      for the pathogenic properties of the autoantibody responses, and interfering with
      this process in individuals at risk may become a route to prevent RA. Recent data
      suggest that interactions between RFs and ACPAs further amplify their
      inflammatory potential.

PMID- 29221598
TI  - The role of ACPAs in at-risk individuals: Early targeting of the bone and joints.
AB  - Autoimmunity precedes inflammation in patients with rheumatoid arthritis (RA),
      opening the possibility to search for early changes in the tissue preceding the
      onset of systemic inflammation. Autoantibodies are important and early drivers of
      bone damage in RA. This article summarizes current evidence for the role of RA
      related autoantibodies in mediating bone loss. Rheumatoid factor (RF) and
      antibodies recognizing modified (citrullinated) proteins have been used as
      diagnostic markers for RA over many years. Their role as pathogenic players,
      however, has long been unrecognized. Recently, several pieces of evidence
      suggested that bone-resorbing osteoclasts are highly responsive to RA-related
      autoantibodies, providing a novel association between autoimmunity and bone.
      These developments have allowed the unraveling of the underlying mechanisms,
      which are responsible for the well-known clinical observation that anti
      citrullinated protein antibodies and RF are associated with a more severe disease
      course. Furthermore, these mechanisms also explain the onset of inflammation in
      the joints of RA patients.

PMID- 29221595
TI  - Genetic and environmental risk factors for rheumatoid arthritis.
AB  - Multiple genetic and environmental factors have been associated with an increased
      risk for rheumatoid arthritis (RA). Of these, the strongest associations have
      been seen with female sex, a family history of RA, the genetic factor the "shared
      epitope," and exposure to tobacco smoke. There is also renewed interest in
      mucosal inflammation and microbial factors as contributors to the development of
      RA. However, the identification of a "preclinical" period of RA that can be
      defined as local or systemic autoimmunity as measured by autoantibodies and other
      biomarkers prior to the development of clinically apparent synovitis suggests
      that the risk factors for RA are acting long prior to first clinical evidence of
      IA. As such, a major challenge to the field will be to investigate the full
      spectrum of the development of RA, from initiation and propagation of
      autoimmunity during preclinical RA and transition to clinically apparent
      synovitis and classifiable RA, to determine which genetic and environmental
      factors are important at each stage of disease development. Understanding the
      exact role and timing of action of risk factors for RA is especially important
      given the advent of prevention trials in RA, and the hope that a full
      understanding of genetic and environmental factors in RA could lead to effective
      preventive interventions.

PMID- 29221599
TI  - Symptoms in individuals at risk of rheumatoid arthritis.
AB  - An increasing interest in treating individuals at risk of rheumatoid arthritis
      (RA) to prevent the development of this chronic condition has focussed attention
      on the identification of risk factors of this disease. Most patients who develop
      RA progress through a preceding symptomatic phase that may take the form of
      arthralgia, palindromic rheumatism or unclassified arthritis before a disease
      currently classifiable as RA is established. An understanding of symptoms that
      identify individuals as being at risk of RA is a critical issue. Constellations
      of relevant symptoms could (1) form the basis of public health campaigns to
      encourage rapid consultation, (2) inform primary health care providers regarding
      which patients to perform additional tests in or whom to refer to a
      rheumatologist and (3) be included in algorithms to predict RA development. In
      this review, we present qualitative and quantitative data summarising current
      understanding of the symptoms experienced by individuals at risk of RA.

PMID- 29221600
TI  - Role of ultrasound imaging in individuals at risk of RA.
AB  - Early diagnosis and treatment improves outcomes for patients with rheumatoid
      arthritis (RA). Studies have shown that musculoskeletal ultrasound is more
      sensitive than clinical examination in identifying synovitis. This review aims to
      address the role of ultrasound in identifying (1) patients with early
      inflammatory arthritis (IA) at risk of progression to RA and (2) those without
      clinical synovitis at risk of progression to early IA and therefore early RA.

PMID- 29221601
TI  - Magnetic resonance imaging in individuals at risk of rheumatoid arthritis.
AB  - Individuals with rheumatoid arthritis (RA) benefit from early diagnosis and
      initiation of therapy. There can be delays in both due to diagnostic
      uncertainties. Imaging modalities, including magnetic resonance imaging (MRI),
      can detect inflammation earlier than clinical examination alone in early RA
      patients. Furthermore, the predictive role of MRI for the future development of
      RA has recently been explored in 'at-risk' individuals. This review details the
      use of MRI in early and undifferentiated arthritis and summarises the studies to
      date in individuals at risk of RA.

PMID- 29221602
TI  - What can palindromic rheumatism tell us?
AB  - Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self
      resolving inflammatory attacks in and around the joints. An association between
      PR and rheumatoid arthritis (RA) has long been postulated; a significant
      proportion of PR patients eventually develop RA and the majority also have anti
      CCP antibodies. Therefore, PR is often considered a prodrome of RA. However, the
      clinical and imaging phenotype of PR has several important distinctions from RA.
      This suggests that despite the similarities, distinct disease mechanisms are at
      play. Given the paucity of evidence-based therapy in PR, a better understanding
      of these mechanisms will be important for refined and targeted therapeutic
      approaches for this important condition.

PMID- 29221603
TI  - Emerging therapies for pre-RA.
AB  - The field of rheumatology has made major contributions to medicine through the
      identification of cellular and molecular targets and the development of therapies
      for the treatment of an impressive range of immune-mediated inflammatory diseases
      such as rheumatoid arthritis. In recent years, new milestones have been achieved.
      These include the recognition of an at-risk state, characterized by disease
      specific autoantibodies in serum and inflammatory joint pain, and the initiation
      of studies seeking to prevent high-risk individuals from progressing to a state
      of clinically apparent arthritis. Here, the current state of the art of
      rheumatoid arthritis prevention is described, highlighting the importance of risk
      stratification and reporting on a growing portfolio of therapeutic interventions
      targeting different stages of the preclinical syndrome.

PMID- 29221604
TI  - Effect of Evolocumab on Lipoprotein Particles.
AB  - The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol
      carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does
      not always correlate with LDL-P because of the variable amounts of cholesterol
      per particle. Consideration of LDL-P concentrations in addition to LDL-C may help
      guide therapeutic decisions in a select number of patients. Evolocumab is a fully
      human monoclonal antibody directed against proprotein convertase subtilisin-kexin
      type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect
      of evolocumab on serum levels and size of lipoprotein particles, we conducted a
      post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody
      Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double
      blind, placebo-controlled, global study of patients with hyperlipidemia. At
      baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100
      nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total
      LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus
      placebo. Evolocumab also reduced concentrations of medium very low-density
      lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density
      lipoprotein particle: median (Q1, Q3) changes were -15.2% (-48, 48), -29% (-54,
      18), and -36% (-70, 22), respectively. Mean (95% confidence interval) % changes
      in total LDL particle size in the evolocumab group was -1.7 (-2.0, -1.4); %
      changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5),
      respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo)
      were all significant (p <0.001). In conclusion, evolocumab significantly lowers
      atherogenic lipoprotein particles including low-density and remnant lipoproteins.

PMID- 29221605
TI  - Significance of High-Sensitivity Troponin T After Elective External Direct
      Current Cardioversion for Atrial Fibrillation or Atrial Flutter.
AB  - External transthoracic direct current (DC) cardioversion is a commonly used
      method of terminating cardiac arrhythmias. Previous research has shown that DC
      cardioversion resulted in myocardial injury as evidenced by increased levels of
      cardiac troponin, even though only minimally. Many of these studies were based on
      the outdated monophasic defibrillators and older, less sensitive troponin assays.
      This study aimed to assess the effect of external transthoracic DC cardioversion
      on myocardial injury as measured by the change in the new high-sensitivity
      cardiac troponin T (hs-cTnT) using the more modern biphasic defibrillators.
      Patients who were admitted for elective DC cardioversion for atrial fibrillation
      or atrial flutter were recruited. Hs-cTnT levels were taken before cardioversion
      and at 6 hours after cardioversion. A total of 120 cardioversions were performed.
      Median (twenty-fifth to seventy-fifth interquartile range) cumulative energy was
      161 J (155 to 532 J). A total of 49 (41%) patients received a cumulative energy
      of 300 J or higher. The median hs-cTnT level before cardioversion was 7 ng/L (4
      to 11 ng/L) and that after cardioversion was 7 ng/L (4 to 10 ng/L). A Wilcoxon
      signed-rank test showed no significant difference between pre- and post
      cardioversion hs-cTnT levels (Z = -0.940, p = 0.347). In conclusion, external DC
      cardioversion did not result in myocardial injury within the first 6 hours as
      measured by high-sensitivity troponin T. Patients who are cardioverted and are
      found to have a significant increase in cardiac troponin after cardioversion
      should be assessed for causes of myocardial injury and not assumed to have
      myocardial injury due to the cardioversion itself.

PMID- 29221607
TI  - Leader-follower formation control of underactuated surface vehicles based on
      sliding mode control and parameter estimation.
AB  - This paper studies the leader-follower formation control of underactuated surface
      vehicles with model uncertainties and environmental disturbances. A parameter
      estimation and upper bound estimation based sliding mode control scheme is
      proposed to solve the problem of the unknown plant parameters and environmental
      disturbances. For each of these leader-follower formation systems, the dynamic
      equations of position and attitude are analyzed using coordinate transformation
      with the aid of the backstepping technique. All the variables are guaranteed to
      be uniformly ultimately bounded stable in the closed-loop system, which is proven
      by the distribution design Lyapunov function synthesis. The main advantages of
      this approach are that: first, parameter estimation based sliding mode control
      can enhance the robustness of the closed-loop system in presence of model
      uncertainties and environmental disturbances; second, a continuous function is
      developed to replace the signum function in the design of sliding mode scheme,
      which devotes to reduce the chattering of the control system. Finally, numerical
      simulations are given to demonstrate the effectiveness of the proposed method.

PMID- 29221608
TI  - A Case of Eruptive Disseminated Porokeratosis in a Cancer Patient after
      Trastuzumab and Exemestane Treatment: Cancer Related or Drug Induced Phenomenon?

PMID- 29221606
TI  - [Medical information system (PMSI) does not adequately identify severe trauma].
AB  - BACKGROUND: Resource allocation to hospitals is highly dependent on appropriate
      case coding. For trauma victims, the major diagnosis-coding category (DCC) is
      multiple trauma (DCC26), which triggers higher funding. We hypothesized that
      DCC26 has limited capacity for appropriate identification of severe trauma
      victims. METHODS: We studied Injury Severity Score (ISS), Trauma Related Injury
      Severity Score (TRISS) and in-hospital mortality using data recorded in three
      level 1 trauma centers over a 2-year period. Patients were divided into two
      groups: DCC26 and non-DCC26. For non-DCC26 patients, two subgroups were
      identified: patients with severe head trauma and patients with spinal trauma.
      Clinical endpoints were mortality, ISS>15 and TRISS, IGS II. Use of hospital
      resources was estimated using funding and expenditures associated with each
      patient. RESULTS: During the study period, 2570 trauma victims were included in
      the analysis. These patients were 39+/-18 years old, with median ISS=14, and
      observed mortality=10 %. Group DCC26 had 811 (31 %) patients, group non-DCC26
      1855 (69 %) patients. DCC26 coding identified a more severely injured group of
      patients. However, in the group non-DCC26, there was a high proportion of severe
      trauma (ISS>15: 35 %; TRISS<0.95: 9 %). CONCLUSION: DCC26 is not an appropriate
      coding for severe trauma patients. For these patients, expenditures will include
      intensive care and rare and costly resources. We propose to take into account the
      TRISS score to improve trauma coding.

PMID- 29221609
TI  - Pitiryasis Lichenoides et Varioliformis Aacuta Associated With Human Herpesvirus
      7.
AB  - Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica
      represent 2 ends of a disease spectrum of unknown etiology. Herein we describe 2
      cases of pityriasis lichenoides et varioliformis acuta, in which human
      herpesvirus 7 DNA was detected in skin samples by polymerase chain reaction
      methodology, an association not previously described. This report may support the
      involvement of viral infection in the etiopathogeny of this disease.

PMID- 29221611
TI  - Resin infiltration is probably effective in reducing the progression of
      noncavitated proximal carious lesions in primary molars.

PMID- 29221612
TI  - Low-level laser therapy may reduce the time of recovery from paresthesia after
      orthognathic surgery.

PMID- 29221610
TI  - Alcohol Misuse and Injury Outcomes in Young People Aged 10-24.
AB  - PURPOSE: The burden of alcohol-attributable disease is a global problem. Young
      people often present to emergency health-care services with alcohol intoxication
      but little is known about how best to intervene at that point to improve future
      health outcomes. This study aimed to assess whether young people with an alcohol
      specific hospital admission are at increased risk of injury following discharge.
      METHODS: A cohort study was conducted using a general population of 10- to 24
      year-olds identified using primary care medical records with linked hospital
      admission records between 1998 and 2013. Exposed individuals had an alcohol
      specific admission. Unexposed individuals did not and were frequency matched by
      age (+/-5 years) and general practice (ratio 10:1). Incidence rates of injury
      related hospital admission post discharge were calculated, and hazard ratios (HR)
      were estimated by Cox regression. RESULTS: The cohort comprised 11,042 exposed
      and 110,656 unexposed individuals with 4,944 injury-related admissions during
      follow-up (2,092 in exposed). Injury rates were six times higher in those with a
      prior alcohol admission (73.92 per 1,000 person-years, 95% confidence interval
      (CI) 70.82-77.16 vs. 12.36, 11.91-12.81). The risk of an injury admission was
      highest in the month following an alcohol-specific admission (adjusted HR =
      15.62, 95% CI 14.08-17.34), and remained higher compared to those with no
      previous alcohol-specific admission at 1 year (HR 5.28 (95% CI 4.97-5.60)) and
      throughout follow-up. CONCLUSIONS: Young people with an alcohol-specific
      admission are at increased risk of subsequent injury requiring hospitalization,
      especially immediately post discharge, indicating a need for prompt intervention
      as soon as alcohol misuse behaviors are identified.

PMID- 29221613
TI  - Immediate loading probably lowers the survival rate of single mandibular implants
      supporting mandibular overdentures compared with delayed loading.

PMID- 29221614
TI  - Using amoxicillin plus metronidazole as an adjunct to nonsurgical periodontal
      treatment results in little benefit, and there seems to be no difference among
      regimens.

PMID- 29221615
TI  - Is exposure to aluminium adjuvants associated with social impairments in mice? A
      pilot study.
AB  - BACKGROUND: Our group has shown that significant correlations exist between rates
      of Autism Spectrum Disorder (ASD) and total aluminum adjuvants given to children
      through vaccines in several Western countries. These correlations satisfied eight
      out of nine Hill criteria for causality. Experimental studies have demonstrated a
      range of behavioural abnormalities in young mice after postnatal exposure to
      aluminium. To build on our previous work, the current study will investigate the
      effect of aluminium adjuvants on social behaviour in mice. Anomalies in social
      interaction are a key characteristic of those with ASD. METHODS: Neonatal CD-1
      mice pups were injected with either a total of 550MUg of aluminum hydroxide gel
      (experimental group) or saline (control) spread out during the first two weeks of
      postnatal life. The mice were then subjected to behavioural tests for social
      interest and social novelty at postnatal week 8, 17 and 29. p-Values were
      calculated using the Mann-Whitney and Kruskal Wallis tests. RESULTS: Aluminum
      injected mice showed diminished social interest compared to controls at week 8
      (p=0.016) and 17 (p=0.012). They also demonstrated abnormal social novelty from
      controls at week 8 (p=0.002) and week 29 (p=0.042). CONCLUSION: This is the first
      experimental study, to our knowledge, to demonstrate that aluminum adjuvants can
      impair social behaviour if applied in the early period of postnatal development.
      The study, however, is insufficient to make any assertive claims about the link
      between aluminium adjuvants and ASD in humans.

PMID- 29221616
TI  - Dengue fever: Report from the task force on tropical diseases by the World
      Federation of Societies of Intensive and Critical Care Medicine.
AB  - Dengue is an arbovirus affecting humans and spread by mosquitoes. Severe dengue
      follows a secondary infection with a different virus serotype. The problem is
      truly global as it is endemic in over 100 countries. Severe dengue can be a life
      threatening because of increased vascular permeability, resulting in leakage of
      fluid from the intravascular compartment to the extravascular space. When major
      bleeding does occur, it is almost invariably combined with profound shock since
      this, in combination with thrombocytopenia, hypoxia, and acidosis, can lead to
      multiple organ failure and disseminated intravascular coagulation. Dengue
      hemorrhagic fever and dengue shock syndrome are among the leading causes of
      morbidity and mortality in patients suffering from Dengue. Commercial rapid tests
      and ELISA kits are freely available, ensuring early diagnosis. The basis of
      management of severe dengue is effective fluid replacement. Future directions in
      management will involve vector control and development of effective vaccination.

PMID- 29221618
TI  - Commentary to 'Urinary tract infection in children: Diagnosis, treatment, imaging
      - Comparison of current guidelines'.

PMID- 29221617
TI  - Minor procedure, major impact: Patient-reported outcomes following urethral
      meatotomy.
AB  - INTRODUCTION: Urethral meatotomy as treatment for meatal stenosis is a common
      pediatric urology procedure; however, little is known about the patient
      experience following this procedure. OBJECTIVE: We aim to evaluate clinical
      factors associated with patient-reported symptom improvement after urethral
      meatotomy. STUDY DESIGN: The families of boys undergoing urethral meatotomy
      between 2/2013 and 8/2016 received a survey by mail 6 weeks after surgery.
      Families were queried on changes in symptoms using a Likert-type scale (5 = much
      improved, 4 = somewhat improved, 3 = no change, 2 = somewhat worse, and 1 = much
      worse). Patient and procedure characteristics of the respondents were obtained
      via chart review. These included surgical indication(s) (abnormal stream,
      dysuria, or storage symptoms), postoperative complications, reoperation, and
      unplanned postoperative communications. Patients who had procedures other than
      simple urethral meatotomy were excluded. Descriptive statistics were compiled,
      and generalized estimating equations used to determine the associations of
      patient and procedure characteristics with symptom improvement. RESULTS: We sent
      629 surveys and received 194 responses (30.4%). Twelve respondents were excluded
      for complex procedures or miscoding. The majority of respondents were privately
      insured (74%) and were between 5 and 12 years old (45%) or 1 and 4 years old
      (42%). The most frequent surgical indication was abnormal stream (72%) followed
      by pain (21%) and storage symptoms (15.5%). Nine respondents had minor
      complications (4.9%). Four patients had restenosis requiring repeat urethral
      meatotomy. After surgery, a majority (79%) were "much improved," 16% were
      "somewhat improved," 3% had "no change," and 1% were "somewhat worse." No family
      reported "much worse." Those patients who had "abnormal stream" as a surgical
      indication were significantly more likely to report "much improved" (OR 1.83, p =
      0.014) than those without. Patient-reported improvement was not associated with
      suture use, patient age, insurance, surgeon, or location of the procedure
      (Table). DISCUSSION: Little has been written about patient-reported outcomes
      following urethral meatotomy. Our study affirms that the majority of boys improve
      following this procedure. However, improvement is significantly more likely if
      the child has a preoperative indication of an abnormal stream, such as deflection
      or spraying. Boys with symptoms of dysuria, frequency, or incontinence may be
      experiencing sequelae of meatal stenosis that simply take longer to improve.
      Alternatively, the meatal stenosis may be incidental to the primary symptoms.
      CONCLUSIONS: A majority of families report substantial symptomatic improvement
      after urethral meatotomy. However, boys undergoing urethral meatotomy for reasons
      other than a urinary stream abnormality are less likely to experience
      improvement.

PMID- 29221619
TI  - Economic susceptibility of fire-prone landscapes in natural protected areas of
      the southern Andean Range.
AB  - Large fires are the most important disturbances at landscape-level due to their
      ecological and socioeconomic impacts. This study aimed to develop an approach for
      the assessment of the socio-economic landscape susceptibility to fire. Our
      methodology focuses on the integration of economic components of landscape
      management based on contingent valuation method (CVM) and net-value change (NVC).
      This former component has been estimated using depreciation rates or changes on
      the number of arrivals to different natural protected areas after a large fire
      occurrence. Landscape susceptibility concept has been motivated by the need to
      assist fire prevention programs and environmental management. There was a
      remarkable variation in annual economic value attributed to each protected area
      based on the CVM scenario, ranging from 40,189-46,887$/year ("Tolhuaca National
      Park") to 241,000-341,953$/year ("Conguillio National Park"). We added landscape
      susceptibility using depreciation rates or tourist arrival decrease which varied
      from 2.04% (low fire intensity in "Tolhuaca National Park") to 76.67% (high fire
      intensity in "Conguillio National Park"). The integration of this approach and
      future studies about vegetation resilience should seek management strategies to
      increase economic efficiency in the fire prevention activities.

PMID- 29221620
TI  - [Nomograms in routine clinical practice: Methodology, interest and limitations].
AB  - In order to help the clinician, mathematical models including several clinical
      and pathological variables are proposed in the literature with the aim to predict
      the occurrence of an event of interest. Nomograms allow individual prognosis for
      each patient. When they are developed, validated and correctly used, nomograms
      can provide important information for patients' care. But, despite the strong
      interest in nomograms in oncology, statistical methodologies used remain unknown
      from the medical community. This paper presents the major steps in the
      development, the validation and the clinical use of nomograms. Examples are given
      to illustrate these different points and the limits of this methodology. Finally,
      guidelines on the use of nomograms are proposed for clinicians.

PMID- 29221621
TI  - [Fertility preservation in oncology].
AB  - Since the improvement of cancer diagnosis and treatment, survival rates of these
      patients increase. Gonadal damages are frequent consequences of cancer treatments
      with different evidence of impaired fertility. In this context, fertility
      preservation should be proposed to patients exposed to potentially gonadotoxic
      treatments. Different preservation approaches may be proposed depending on
      patient age, sex, cancer type and type of treatment. The indications of fertility
      preservation depend on sexual maturity. In young girls, ovarian cortex
      cryopreservation is the only technique feasible in order to preserve their
      reproductive potential. Vitrification of oocytes which needs ovarian stimulation
      or oocytes in vitro maturation is becoming more commonly performed for pubertal
      women to preserve their fertility. Ovarian cortex freezing could be offered to
      emergency fertility preservation of adult female cancer patients. In prepubertal
      boys, testicular tissue cryopreservation is the only line treatment for fertility
      preservation. For future use, various approaches are being evaluated such as
      spermatogonial stem cell injection or in vitro maturation. Cryopreservation of
      spermatozoa is, today, an established and successful technique for male adults.
      When there are no spermatozoa in ejaculate, sperm can be retrieved after
      treatment of testicular biopsy. The French bioethics law clearly indicates that
      fertility preservation should be proposed to patients exposed to potentially
      gonadotoxic treatment. Today, many approaches are possible. Fertility
      preservation indications are based on multidisciplinary consultations within
      platforms for the fertility preservation in order to optimize the patient care.

PMID- 29221622
TI  - Editorial overview: Protein-nucleic acid interactions: An expanding universe.

PMID- 29221623
TI  - Editorial overview: Catalysis and regulation.

PMID- 29221624
TI  - International Medical Graduates in Nephrology: Roles, Rules, and Future Risks.
AB  - International medical graduates (IMGs) have become an increasingly essential part
      of many residency and fellowship programs in the United States. IMGs, who may be
      of either US or non-US citizenship, contribute significantly to the physician
      workforce across this country, particularly in underserved areas, as well as in
      their home countries on their return after training. Approximately 65% of
      nephrology fellows are IMGs, with most of these being non-US citizens. Non-US IMG
      applications for nephrology fellowship have been declining, exacerbating an
      ongoing shortage of nephrology trainees. IMGs face visa status restrictions and
      immigration policy concerns, limitations on federally funded research support,
      and difficulty finding desirable jobs in both private practices and academia
      after fellowship. We review training, examination, and licensure requirements, as
      well as visa status rules for IMGs. We also discuss the potential negative impact
      of recent immigration policies limiting the entry of non-US IMGs on the medical
      community in general and in nephrology in particular.

PMID- 29221625
TI  - Population Health for CKD and Diabetes: Lessons From the Indian Health Service.
AB  - Despite extensive clinical guidelines, innovative efforts to improve care, and
      well-funded efforts to raise awareness, limited progress has been made in
      reducing the burden of kidney disease in the United States, and the prevalence
      continues to increase worldwide. The Indian Health Service and the Centers for
      Disease Control and Prevention recently reported a 54% decrease in the incidence
      of kidney failure among American Indian and Alaska Native people with diabetes.
      This decrease in end-stage renal disease incidence was associated with a
      population health approach to diabetes care based in the community and the
      primary clinical setting. The effort focused on integrating better care for
      kidney disease within the context of routine diabetes care. Although the American
      Indian population and the Indian Health Service may be unfamiliar to many
      clinicians and health system administrators, the demonstration that simple
      evidence-based interventions implemented in a comprehensive and consistent way
      can reduce the burden of end-stage renal disease suggests that population-based
      approaches to chronic disease offer significant potential benefits. Large
      pragmatic trials may offer the best way to rigorously test this hypothesis.

PMID- 29221626
TI  - Effects of Oral Nutritional Supplements on Mortality, Missed Dialysis Treatments,
      and Nutritional Markers in Hemodialysis Patients.
AB  - OBJECTIVE: Protein-energy wasting is common in end-stage renal disease patients
      undergoing dialysis and is strongly associated with mortality and adverse
      outcomes. Intradialytic oral nutritional supplements (ONS) reduce risk of
      mortality in these patients. Large studies characterizing the impact of ONS on
      other outcomes are lacking. We assessed the associations between administration
      of ONS and clinical and nutritional outcomes. DESIGN: Retrospective evaluation of
      a pilot program providing ONS to patients at a large dialysis organization in the
      United States. The pilot program provided ONS to in-center hemodialysis patients
      with serum albumin <=3.5 g/dL at 408 facilities. SUBJECTS: ONS patients were
      compared to matched controls with serum albumin <=3.5 g/dL, identified from
      facilities not participating in the ONS program (n = 3,374 per group).
      INTERVENTION: Receipt of ONS. MAIN OUTCOME MEASURES: Death, missed dialysis
      treatments, hospitalizations, serum albumin, normalized protein catabolic rate,
      and postdialysis body weight were abstracted from large dialysis organization
      electronic medical records. RESULTS: There was a 69% reduction in deaths (hazard
      ratio = 0.31; 95% confidence interval = 0.25-0.39), and 33% fewer missed dialysis
      treatments (incidence rate ratio = 0.77; 95% confidence interval = 0.73-0.82)
      among ONS patients compared to controls (P < .001 for both). The effects of ONS
      on nutritional indices were mixed: serum albumin was lower, whereas normalized
      protein catabolic rate values, a surrogate for dietary protein intake, and
      postdialysis body weights were higher for ONS patients compared to controls
      during follow-up. CONCLUSIONS: Our evaluation confirmed the beneficial effects of
      ONS in reducing mortality and improving some indices of nutritional status for
      hypoalbuminemic hemodialysis patients. We also report the novel finding that ONS
      can reduce the number of missed dialysis treatments. These results support the
      use of intradialytic ONS as an effective intervention to improve the outcomes in
      hemodialysis patients with low serum albumin.

PMID- 29221627
TI  - Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional
      Management of Chronic Kidney Disease.
AB  - The kidneys play an extremely important role in maintaining the body acid-base
      balance by excreting nonvolatile acids and regenerating and reabsorbing
      bicarbonate in the kidney tubules. As the individual loses their kidney function,
      renal excretion of nonvolatile acid produced by metabolism of the diet is
      impaired, resulting in low-grade metabolic acidosis. With this in mind, it is
      relevant to better understand the dietary aspects related to the acid-base
      balance in chronic kidney disease metabolic acidosis and try to provide possible
      strategies for the nutritional management of these cases. The type of diet can
      deeply affect the body by providing acid or base precursors. Generally speaking,
      foods such as meat, eggs, cheese, and grains increase the production of acid in
      the organism, whereas fruit and vegetables are alkalizing. On the other hand,
      milk is considered neutral as well as fats and sugars, which have a small effect
      on acid-base balance. The modern Western-type diet is deficient in fruits and
      vegetables and contains excessive animal products. Thus metabolic acidosis may be
      exacerbated by a contemporary Western diet, which delivers a high nonvolatile
      acid load. The remaining acid is neutralized or stored within the body. Bone and
      muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies
      suggest that lowering the dietary acid load with a reduced protein content and
      vegetable proteins replacements, associated with an increase in fruits and
      vegetables intake can improve the metabolic parameters of acidosis, preserve bone
      and muscle, and slow the glomerular filtration rate decline. More studies
      focusing on the effects of controlled dietary interventions among chronic kidney
      disease patients are needed to determining the optimal target for nutritional
      therapy.

PMID- 29221628
TI  - Recommendations for the implantation of leadless pacemakers from the French
      Working Group on Cardiac Pacing and Electrophysiology of the French Society of
      Cardiology.

PMID- 29221630
TI  - Enrichment of 57Fe isotope in neutron flux of nuclear reactors observed by
      Mossbauer spectroscopy.
AB  - The abundance of 57Fe isotope in nuclear reactor core materials can be
      considerably enriched by neutron-capture 56Fe(n,gamma) reactions. This is
      demonstrated using the sections of Zr-2.5 wt.%Nb pressure tubes removed from two
      CANDU* reactors. The tubes contained 0.11 and 0.04wt% Fe and were irradiated for
      about 10 effective full power years (EFPY) up to ~1026n/m2 fast neutron (E >
      1MeV) fluencies. The Mossbauer spectra of 57Fe in irradiated samples indicated up
      to 10 times larger areas than unirradiated off-cuts from the same pressure tubes.
      The observed effect is in accord with the values calculated for known thermal
      neutron-capture cross-sections and resonance capture integrals, neutron flux
      profiles and spectra, and times of irradiation. The build-up of 57Fe facilitated
      recording Mossbauer absorption spectra of alloys with minor amount of Fe down to
      ~ 400ppm, despite intense background radiation emitted by samples. These findings
      can open new possibilities in post-irradiation studies of alloys used in nuclear
      reactors and in other objects subjected to large neutron fluencies.

PMID- 29221629
TI  - 224th ENMC International Workshop:: Clinico-sero-pathological classification of
      immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October
      2016.

PMID- 29221631
TI  - A population-based evaluation of the natural history of chronic pancreatitis.
AB  - BACKGROUND: Based on reports from tertiary care centers, chronic pancreatitis
      (CP) is considered to be a painful and debilitating disease frequently requiring
      invasive interventions. Our primary aim was to assess the natural course of CP in
      a population-based cohort using endoscopic and surgical interventions as
      surrogates for disease aggressiveness. METHODS: We identified all patients (n =
      89, alcoholic [ACP = 46], non-alcoholic [NACP] = 43) with newly diagnosed
      definite CP from Olmsted County, Minnesota between 1977 and 2006. Patients were
      followed until death or censoring. Medical records were reviewed at time of
      diagnosis and during each follow-up. Both lifetime proportions and cumulative
      incidence since the initial manifestation of CP were estimated and compared.
      Survival was estimated with Kaplan-Meier methodology. RESULTS: Median age at CP
      diagnosis was 56 years (IQR, 48-67) and 56% were male. During median follow-up of
      10 years, 68 (76%) experienced pancreatic pain, but only 27 (30%) needed any
      invasive therapeutic intervention: 23% had endotherapy and 11% had pancreatic
      surgery. During the clinical course, when compared with NACP, ACP patients had
      significantly more (all p < 0.05) pain (87 vs. 65%), recurrent acute pancreatitis
      (44 vs. 23%), pseudocysts (41 vs. 16%), cumulative incidence of exocrine
      insufficiency (60 vs. 21%), and annual hospitalizations after CP diagnosis (0.79
      vs. 0.25). The cumulative risk of diabetes, calcifications, surgery and overall
      survival was similar in ACP and NACP. CONCLUSIONS: Our study suggests that CP at
      a population level may have a milder course than that reported from tertiary
      centers. We confirm that ACP has a more severe phenotype than NACP.

PMID- 29221632
TI  - Transarterial chemoembolization in pancreatic adenocarcinoma with liver
      metastases: MR-based tumor response evaluation, apparent diffusion coefficient
      (ADC) patterns, and survival rates.
AB  - PURPOSE: To retrospectively investigate the effectiveness of triple drug
      combination transarterial chemoembolization (TACE) on local tumor response and
      survival in patients with liver metastases from pancreatic cancer. Also, this
      study will evaluate the variances in response regarding the number of metastases,
      assess the correlation between tumor response and the changes in the apparent
      diffusion coefficients (ADC) in diffusion weighted (DW) MRI. MATERIALS AND
      METHODS: One hundred and twelve patients (58 men and 54 women; mean age 57) with
      malignant liver metastases from pancreatic adenocarcinoma underwent at least one
      session of TACE with a chemotherapeutic combination of mitomycin C, cisplatin,
      and gemcitabine. A size-based evaluation of tumor response (response evaluation
      criteria in solid tumors (RECIST)) was conducted, along with ADC values, and
      survival indices as related to treatment pattern. RESULTS: Four weeks following
      the end of the treatment, 78.26% of patients showed stable disease and 11.59%
      showed partial response. The median survival time was 19 months and for the
      stable disease group, 26 months. Low pretreatment ADC values showed no
      significant correlation to poor response to treatment (r = 0.347,p = 0.146).
      CONCLUSION: The triple drug TACE technique showed improvements in median survival
      times in patients with hepatic metastases from pancreatic carcinoma and helped
      control disease progression, whereas the number of hepatic lesions was not a
      statistically significant factor in patients' response to TACE. The data suggest
      that pre-treatment ADC values in DW-MRI have no statistical correlation with
      tumor response.

PMID- 29221634
TI  - [Point-of-care ultrasound for suspected secondary arterial hypertension].

PMID- 29221635
TI  - Relationship between duration of second stage of labour and postpartum anaemia.
AB  - AIM: To assess the relationship between the duration of the second stage of
      labour and postpartum anaemia during vaginal birth. METHODS: An observational,
      analytical retrospective cohort study was performed at the "Mancha-Centro
      Hospital" (Spain) during the 2013-2016 period. Data were collected from 3437
      women who had a vaginal birth. Postpartum anaemia was defined as a haemoglobin
      level below 11g/dL at 24h postpartum. A univariate analysis was used for
      potential risk factors and a multivariate analysis with binary logistic
      regression to control for possible confounding factors. FINDINGS: The incidence
      of postpartum anaemia was 42.0%. The risk of postpartum anaemia did not increase
      in nulliparous women whose duration of the second stage of labour exceeded 4h.
      Compared with multiparous women who delivered between 0 and 3h, multiparous women
      with a duration of the second stage of labour beyond 3h were at higher risk of
      postpartum anaemia (OR=2.43 [1.30-4.52]). CONCLUSION: The duration of the second
      stage of labour beyond 4h is safe for postpartum anaemia in nulliparous women.
      However in multiparous women, monitoring should increase if the second stage of
      labour exceeds 3h given the increased risk of postpartum anaemia.

PMID- 29221633
TI  - Proteases of Sporothrix schenckii: Cytopathological effects on a host-cell model.
AB  - BACKGROUND: Sporotrichosis is a fungal infection caused by the Sporothrix
      schenckii complex. The adhesion of the fungus to the host tissue has been
      considered the key step in the colonization and invasion, but little is known
      about the early events in the host-parasite interaction. AIMS: To evaluate the
      proteolytic activity of S. schenckii on epithelial cells. METHODS: The
      proteolytic system (at pH 5 and 7) was evaluated using azocoll and zymograms. The
      host-parasite interaction and epithelial cell response were also analyzed by
      examining the microfilament cytoskeleton using phalloidin-FITC and transmission
      electron microscopy. Finally, the metabolic activity was determined using an XTT
      assay. RESULTS: The zymograms showed that S. schenckii yeast cells possess high
      intracellular and extracellular proteolytic activities (Mr>=200, 116, 97, and
      70kDa) that are pH dependent and are inhibited by PMSF and E64, which act on
      serine and cysteine-type proteases. During the epithelial cell-protease
      interaction, the cells showed alterations in the microfilament distribution, as
      well as in the plasma membrane structure. Moreover, the metabolic activity of the
      epithelial cells decreased 60% without a protease inhibitor. CONCLUSIONS: Our
      data demonstrate the complexity of the cellular responses during the infection
      process. This process is somehow counteracted by the action of proteases
      inhibitors. Furthermore, the results provide critical information for
      understanding the nature of host-fungus interactions and for searching a new
      effective antifungal therapy, which includes protease inhibitors.

PMID- 29221636
TI  - Urothelial neoplasms in pediatric and young adult patients: A large single-center
      series.
AB  - PURPOSE: Bladder cancer is the sixth most common cancer in the United States, but
      is exceedingly rare in young patients, leading to a lack of accepted standards
      for diagnosis, treatment, and surveillance. We review our institutional
      experience with bladder urothelial neoplasms in pediatric and young adult
      patients summarizing presentation, treatment, and outcomes. METHODS: Surgical
      pathology records at our institution were searched for cases of urothelial
      neoplasms among patients <=25 years of age treated between January 1997 and
      September 2016. Cases submitted exclusively for pathology review were excluded.
      Diagnoses were confirmed based on pathologic examination using the 2004 World
      Health Organization classification system. RESULTS: Thirty-four patients were
      identified with a mean age of 21.1 years (range 8-25 years), and median follow-up
      was 25.1 months (1-187 months). The male to female ratio was 1.83:1. The most
      common presenting symptom was hematuria (n=26; 76%). Diagnoses were invasive
      urothelial carcinoma (n=3), noninvasive urothelial carcinoma (n=24), PUNLMP
      (n=6), and urothelial papilloma (n=1). Noninvasive lesions were resected by
      cystoscopy, after which 12% (n=4) experienced complications (grade II or
      greater). One patient with stage IV invasive disease at diagnosis died, and 2
      patients developed recurrences. Of those with noninvasive carcinoma, 29% (n=7)
      required repeat cystoscopy soon after initial TURBT at outside institutions, and
      17% (n=4) had tumors downgraded from high-grade to low-grade after pathology
      review. CONCLUSION: Hematuria is the most common sign of bladder neoplasia in
      children and young adults and should be investigated by cystoscopy. The majority
      of urothelial neoplasms in these patients are noninvasive and can be successfully
      treated with transurethral resection. LEVEL OF EVIDENCE: Level IV (Retrospective
      study with no comparison group).

PMID- 29221637
TI  - Effect of previous abdominal surgery and gallbladder appearance on biliary
      atresia outcomes.
AB  - BACKGROUND: Biliary atresia (BA) is typically treated by Kasai portoenterostomy
      (KPE), and there is a relationship between age at surgery and outcome. We
      hypothesize that previous abdominal surgery (PAS) for associated congenital
      intestinal conditions could be used to identify BA earlier, perhaps improving
      prognosis. METHODS: A retrospective case note review was performed of all BA
      patients at a single centre from 1999 to 2016. Demographics and clinical outcome
      data were collected. Additional data on laparotomy, parenteral nutrition, and
      referral were collected from patients who underwent PAS. Data are median (range).
      MAIN RESULTS: Two-hundred-and-fifty-seven children were reviewed. Of these, 16
      (6.2%) underwent PAS on day 3 (0-23), during which 5 atretic gallbladders were
      noted. Gallbladder appearance was not referenced in the operation notes of 8
      infants. Jaundice and acholic stools were noted at 4 (0-56) days and 21 (0-60)
      days, respectively. Age at KPE was comparable between PAS and the other patients
      (50 vs. 51days; P=0.78), but native liver survival was significantly lower after
      PAS (p<0.0001). Mortality rate was higher in PAS patients (25% vs. 4.5%;
      P=0.0007). Survival was unaffected by early referral of patients on finding an
      atretic gallbladder at surgery. CONCLUSION: About 6% of infants have already
      undergone abdominal surgery for biliary atresia associated intestinal anomalies.
      Routine gallbladder examination at time of laparotomy could have aided earlier
      diagnosis and treatment of biliary atresia in up to 80% of patients in this
      cohort. However, our data suggest that clinical outcome is poorer in biliary
      patients who undergo prior abdominal surgery and is not improved by earlier
      referral. LEVEL OF EVIDENCE: Prognostic study: Level III.

PMID- 29221638
TI  - D-dimer level correlation with treatment response in children with venous
      malformations.
AB  - AIM: Localized intravascular coagulopathy is present in children with venous
      malformations (VMs) as evidenced by elevated D-dimer levels. Few studies have
      looked into the changes in D-dimer after sclerotherapy and its correlation with
      treatment outcome and complications. Our study aims to investigate changes in D
      dimer in children with VMs undergoing alcohol sclerotherapy. METHODS: A
      prospective cohort study from 2014 to 2016, which included children (<18years)
      with VM undergoing alcohol sclerotherapy, was completed. Demographics and lesion
      characteristics were recorded. Perioperative D-dimer levels were collected 2weeks
      prior to treatment (baseline) and on postoperative days 1, 2, 5, and 14,
      respectively. A raised postoperative D-dimer was defined as a peak level of at
      least 50% increase of baseline D-dimer. Children were followed up with
      documentation of lesional size at 6months and long-term recurrence beyond 6months
      of treatment. RESULTS: Eighteen children were identified (10 females, 8 males)
      with a median follow up of 21months. Overall, 15 patients (83%) had a
      satisfactory outcome. Baseline D-dimer levels were high in 8 patients (44%).
      Postoperative D-dimer level was raised in 12 patients irrespective of their
      baseline levels, with 92% peaking on postoperative day one (n=11). In the
      elevated D-dimer group, 11 patients had a satisfactory outcome, and 10 patients
      did not have long-term recurrence. We did not encounter any complications in our
      cohort. CONCLUSION: Changes in perioperative D-dimer levels may predict early
      treatment response and long-term recurrence after alcohol sclerotherapy. With a
      standardized protocol, alcohol sclerotherapy for venous malformation is safe with
      minimal complications. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: IV.

PMID- 29221639
TI  - Nerve growth factor released from collagen scaffolds protects axotomized
      cholinergic neurons of the basal nucleus of Meynert in organotypic brain slices.
AB  - BACKGROUND: Alzheimers disease is accompanied by cell death of cholinergic
      neurons, resulting in cognitive impairment and memory loss. Nerve growth factor
      (NGF) is the most potent protein to support survival of cholinergic neurons. NEW
      METHOD: Organotypic brain slices of the basal nucleus of Meynert (nBM) are a
      valuable tool to study cell death of axotomized cholinergic neurons, as well as
      protective effects of NGF added into the medium. The aim of the present study is
      to use collagen scaffolds crosslinked with polyethyleneglycole and load with NGF
      to target delivery of NGF to organotypic nBM brain slices. RESULTS: Collagen
      scaffolds (visualized by incorporating AlexaFluor 488 antibodies) slowly degraded
      when applied onto organotypic brain slices within 2 weeks in culture. GFAP
      reactive astrocytes and Iba1+ microglia became visible around the collagen
      scaffolds 7days after incubation, showing reactive gliosis. Cholinergic neurons
      of the nBM survived (201+/-21, n=8) when incubated with 100ng/ml NGF in the
      medium compared to NGF-free medium (69+/-12, n=7). Collagen scaffolds loaded with
      NGF (1ng/2MUl scaffold) significantly rescued cholinergic cell death in the nBM
      brain slices (175+/-12, n=10), which was counteracted by an anti-NGF antibody
      (77+/-5, n=5). COMPARISON WITH EXISTING METHODS: The combination of coronal brain
      slices with biomaterial is a novel and potent tool to selectively study
      neuroprotective effects. CONCLUSIONS: Collagen scaffolds loaded with low amounts
      of a protein/drug of interest can be easily applied directly onto organotypic
      brain slices, allowing slow targeted release of a protective molecule. Such an
      approach is highly useful to optimize CollScaff for further in vivo applications.

PMID- 29221640
TI  - Threshold-based segmentation of fluorescent and chromogenic images of microglia,
      astrocytes and oligodendrocytes in FIJI.
AB  - BACKGROUND: Image segmentation is often imperfect, particularly in complex image
      sets such z-stack micrographs of slice cultures and there is a need for
      sufficient details of parameters used in quantitative image analysis to allow
      independent repeatability and appraisal. NEW METHOD: For the first time, we have
      critically evaluated, quantified and validated the performance of different
      segmentation methodologies using z-stack images of ex vivo glial cells. The
      BioVoxxel toolbox plugin, available in FIJI, was used to measure the relative
      quality, accuracy, specificity and sensitivity of 16 global and 9 local threshold
      automatic thresholding algorithms. RESULTS: Automatic thresholding yields
      improved binary representation of glial cells compared with the conventional user
      chosen single threshold approach for confocal z-stacks acquired from ex vivo
      slice cultures. The performance of threshold algorithms varies considerably in
      quality, specificity, accuracy and sensitivity with entropy-based thresholds
      scoring highest for fluorescent staining. COMPARISON WITH EXISTING METHODS: We
      have used the BioVoxxel toolbox to correctly and consistently select the best
      automated threshold algorithm to segment z-projected images of ex vivo glial
      cells for downstream digital image analysis and to define segmentation quality.
      The automated OLIG2 cell count was validated using stereology. CONCLUSIONS: As
      image segmentation and feature extraction can quite critically affect the
      performance of successive steps in the image analysis workflow, it is becoming
      increasingly necessary to consider the quality of digital segmenting
      methodologies. Here, we have applied, validated and extended an existing
      performance-check methodology in the BioVoxxel toolbox to z-projected images of
      ex vivo glia cells.

PMID- 29221641
TI  - p53-expression in patients with renal cell carcinoma correlates with a higher
      probability of disease progression and increased cancer-specific mortality after
      surgery but does not enhance the predictive accuracy of robust outcome models.
AB  - OBJECTIVE: Due to lacking external validation, molecular biomarkers are currently
      not applied for risk-stratification of patients with localized renal cell
      carcinoma. The objective of this study was to externally validate a molecular
      multi-marker panel included in a previously proposed prognostic nomogram for the
      prediction of postoperative disease-free survival. METHODS AND MATERIALS: Besides
      pathologic tumor stage (pT) and ECOG-Performance Status, the nomogram includes 5
      molecular markers (Ki-67, p53, VEGFR-1 endothelial or epithelial, and VEGF-D
      epithelial). The validation cohort comprised 343 renal cell carcinoma patients
      treated by radical nephrectomy or nephron-sparing surgery from 1999 to 2004 at a
      single academic center (median follow-up: 100 months). By multivariable Cox
      proportional-hazards regression models, the impact of clinical and molecular
      markers included in the nomogram on disease progression (DP) and cancer-specific
      mortality (CSM) was assessed; in addition, it was evaluated to what extent
      molecular markers added to the models' predictive accuracy (PA). RESULTS: Of all
      parameters included in the nomogram, ECOG-PS and pT-stage only revealed a
      significant impact on both endpoints. p53 (per 10% measures) showed a significant
      impact on DP (HR = 1.31; P = 0.008), albeit not on CSM, while all other molecular
      markers did not impact study endpoints. Using Martingale residuals, a cut-off
      value for p53-expression<20% (negative) vs. >=20% (positive) yielded the highest
      impact on DP and CSM. In outcome-models including further well-established histo
      pathological factors, p53-expression dichotomized at 20% independently impacted
      DP (HR = 4.13; P = 0.004) and CSM (HR = 3.74; P = 0.033), while no significant PA
      gain was achieved. CONCLUSIONS: p53 showed a statistically significant impact on
      DP, albeit not on CSM, when applying the 10% expression cut-off as used in the
      original nomogram, while the prognostic value of all other examined markers
      included in the nomogram could not be confirmed. When an alternative cut-off of
      20% was applied in multivariable models, p53 independently impacted DP and CSM,
      while the PA was not significantly enhanced. Hence, the clinical significance of
      p53 is still to be determined. Based on the results of this study it is not
      recommendable to use p53-expression and the Klatte nomogram in routine clinical
      decision-making.

PMID- 29221642
TI  - Impact of age on outcomes of patients with non-muscle-invasive bladder cancer
      treated with immediate postoperative instillation of mitomycin C.
AB  - OBJECTIVES: To evaluate whether age affects the clinical benefit afforded by
      immediate postoperative intravesical instillation of mitomycin C in a
      contemporary cohort of patients with NMIBC. PATIENTS AND METHODS: A total of
      4,258 patients with NMIBC treated with transurethral resection of the bladder
      with (n = 2,605, 61%) or without (n = 1,652, 39%) one immediate instillation of
      mitomycin C from 5 institutions (study period: 2000-2007) were included. No
      patients received adjuvant instillations. A multivariable Cox proportional
      hazards regression model adjusting for standard clinical and pathological
      features tested the potential interaction term between age and administration of
      mitomycin C with regard to disease recurrence. RESULTS: A total of 2,063 patients
      experienced disease recurrence with a median follow-up of 48 months for those who
      did not recur. In multivariable Cox regression analysis, immediate postoperative
      instillation of mitomycin C (HR: 0.62; 95% CI: 0.56-0.68; P<0.0001) and age (HR:
      1.04; 95% CI: 1.00-1.09; P = 0.036) were associated with disease recurrence. We
      observed only slight decreases in recurrence-free survival with age irrespective
      of treatment administration of mitomycin C or not. CONCLUSION: We confirmed
      reduced disease recurrence rates associated with 1 immediate postoperative
      intravesical instillation of mitomycin C in NMIBC patients. The benefit on
      recurrence-free survival of a postoperative intravesical instillation was
      preserved across all ages and therefore age by itself should not be taken into
      consideration when deciding to use it.

PMID- 29221644
TI  - Disease Control Priorities, 3rd edition-from theory to practice.

PMID- 29221643
TI  - Respiratory and cardiovascular responses to walking down a traffic-polluted road
      compared with walking in a traffic-free area in participants aged 60 years and
      older with chronic lung or heart disease and age-matched healthy controls: a
      randomised, crossover study.
AB  - BACKGROUND: Long-term exposure to pollution can lead to an increase in the rate
      of decline of lung function, especially in older individuals and in those with
      chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at
      higher pollution levels has been implicated in causing excess deaths from
      ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects
      on respiratory and cardiovascular responses of walking down a busy street with
      high levels of pollution compared with walking in a traffic-free area with lower
      pollution levels in older adults. METHODS: In this randomised, crossover study,
      we recruited men and women aged 60 years and older with angiographically proven
      stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung
      Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched
      healthy volunteers. Individuals with ischaemic heart disease or COPD were
      recruited from existing databases or outpatient respiratory and cardiology
      clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched
      healthy volunteers using advertising and existing databases. All participants had
      abstained from smoking for at least 12 months and medications were taken as
      recommended by participants' doctors during the study. Participants were randomly
      assigned by drawing numbered disks at random from a bag to do a 2 h walk either
      along a commercial street in London (Oxford Street) or in an urban park (Hyde
      Park). Baseline measurements of participants were taken before the walk in the
      hospital laboratory. During each walk session, black carbon, particulate matter
      (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2)
      concentrations were measured. FINDINGS: Between October, 2012, and June, 2014, we
      screened 135 participants, of whom 40 healthy volunteers, 40 individuals with
      COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black
      carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street
      than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR]
      1.95, 95% CI 0.96-3.95; p<0.1), sputum (3.15, 1.39-7.13; p<0.05), shortness of
      breath (1.86, 0.97-3.57; p<0.1), and wheeze (4.00, 1.52-10.50; p<0.05) after
      walking down Oxford Street compared with Hyde Park. In all participants,
      irrespective of their disease status, walking in Hyde Park led to an increase in
      lung function (forced expiratory volume in the first second [FEV1] and forced
      vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and
      augmentation index up to 26 h after the walk. By contrast, these beneficial
      responses were attenuated after walking on Oxford Street. In participants with
      COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with
      an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an
      increase in PWV and augmentation index with NO2 and ultrafine particles. In
      healthy volunteers, PWV and augmentation index were associated both with black
      carbon and ultrafine particles. INTERPRETATION: Short-term exposure to traffic
      pollution prevents the beneficial cardiopulmonary effects of walking in people
      with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary
      diseases. Medication use might reduce the adverse effects of air pollution in
      individuals with ischaemic heart disease. Policies should aim to control ambient
      levels of air pollution along busy streets in view of these negative health
      effects. FUNDING: British Heart Foundation.

PMID- 29221646
TI  - Remission of type 2 diabetes: mission not impossible.

PMID- 29221645
TI  - Primary care-led weight management for remission of type 2 diabetes (DiRECT): an
      open-label, cluster-randomised trial.
AB  - BACKGROUND: Type 2 diabetes is a chronic disorder that requires lifelong
      treatment. We aimed to assess whether intensive weight management within routine
      primary care would achieve remission of type 2 diabetes. METHODS: We did this
      open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in
      Scotland and the Tyneside region of England. Practices were randomly assigned
      (1:1), via a computer-generated list, to provide either a weight management
      programme (intervention) or best-practice care by guidelines (control), with
      stratification for study site (Tyneside or Scotland) and practice list size
      (>5700 or <=5700). Participants, carers, and research assistants who collected
      outcome data were aware of group allocation; however, allocation was concealed
      from the study statistician. We recruited individuals aged 20-65 years who had
      been diagnosed with type 2 diabetes within the past 6 years, had a body-mass
      index of 27-45 kg/m2, and were not receiving insulin. The intervention comprised
      withdrawal of antidiabetic and antihypertensive drugs, total diet replacement
      (825-853 kcal/day formula diet for 3-5 months), stepped food reintroduction (2-8
      weeks), and structured support for long-term weight loss maintenance. Co-primary
      outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as
      glycated haemoglobin (HbA1c) of less than 6.5% (<48 mmol/mol) after at least 2
      months off all antidiabetic medications, from baseline to 12 months. These
      outcomes were analysed hierarchically. This trial is registered with the ISRCTN
      registry, number 03267836. FINDINGS: Between July 25, 2014, and Aug 5, 2017, we
      recruited 306 individuals from 49 intervention (n=23) and control (n=26) general
      practices; 149 participants per group comprised the intention-to-treat
      population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%)
      participants in the intervention group and no participants in the control group
      (p<0.0001). Diabetes remission was achieved in 68 (46%) participants in the
      intervention group and six (4%) participants in the control group (odds ratio
      19.7, 95% CI 7.8-49.8; p<0.0001). Remission varied with weight loss in the whole
      study population, with achievement in none of 76 participants who gained weight,
      six (7%) of 89 participants who maintained 0-5 kg weight loss, 19 (34%) of 56
      participants with 5-10 kg loss, 16 (57%) of 28 participants with 10-15 kg loss,
      and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by
      10.0 kg (SD 8.0) in the intervention group and 1.0 kg (3.7) in the control group
      (adjusted difference -8.8 kg, 95% CI -10.3 to -7.3; p<0.0001). Quality of life,
      as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7.2
      points (SD 21.3) in the intervention group, and decreased by 2.9 points (15.5) in
      the control group (adjusted difference 6.4 points, 95% CI 2.5-10.3; p=0.0012).
      Nine serious adverse events were reported by seven (4%) of 157 participants in
      the intervention group and two were reported by two (1%) participants in the
      control group. Two serious adverse events (biliary colic and abdominal pain),
      occurring in the same participant, were deemed potentially related to the
      intervention. No serious adverse events led to withdrawal from the study.
      INTERPRETATION: Our findings show that, at 12 months, almost half of participants
      achieved remission to a non-diabetic state and off antidiabetic drugs. Remission
      of type 2 diabetes is a practical target for primary care. FUNDING: Diabetes UK.

PMID- 29221647
TI  - Walking to a pathway for cardiovascular effects of air pollution.

PMID- 29221649
TI  - [Two cases of granuloma annulare under anti-PD1 therapy].
AB  - BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug
      induced. Immune checkpoint inhibitors including programmed death-1 (PD-1)
      inhibitors show remarkable antitumor activity and are approved for melanoma and
      other cancers. Different immune-related adverse effects have been described. We
      report herein a rare adverse effect of anti-PD1 therapy given for metastatic
      melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving
      pembrolizumab metastatic melanoma presented with granuloma annulare. The therapy
      was continued in both cases. In the first patient, granuloma annulare appeared
      and then subsided; in the second patient, the lesion resolved completely with
      topical corticosteroids. DISCUSSION: While there have been reported cases of
      sarcoidosis induced by immunotherapies, immunotherapy-induced granuloma annulare
      has not been described. The pathogenesis of drug-induced granulomatous reactions
      is thought to involve autoimmune dysregulation affecting T cells, especially Th1
      cells, which lead to granuloma formation. Granuloma annulare should thus be
      considered a cutaneous adverse effect of anti-PD1 immunotherapy.

PMID- 29221648
TI  - Benefit of using motion compensated reconstructions for reducing inter-observer
      and intra-observer contouring variation for organs at risk in lung cancer
      patients.
AB  - BACKGROUND AND PURPOSE: In lung cancer patients, accuracy in contouring is
      hampered by image artefacts introduced by respiratory motion. With the widespread
      introduction of 4DCT there is additional uncertainty caused by the use of
      different reconstruction techniques which will influence contour definition. This
      work aims to assess both inter- and intra-observer contour variation on average
      and motion compensated (mid-position) reconstructions. MATERIAL AND METHODS:
      Eight early stage non-small cell lung cancer patients that received 4DCT were
      selected and these scans were reconstructed as average and motion compensated
      datasets. 5 observers contoured the organs at risk (trachea, oesophagus, proximal
      bronchial tree, heart and brachial plexus) for each patient and each
      reconstruction. Contours were compared against a STAPLE volume with distance to
      agreement metrics. Intra-observer variation was assessed by redelineation after 4
      months. RESULTS: The inter-observer variation was significantly smaller using the
      motion compensated datasets for the trachea (p = 0.006) and proximal bronchial
      tree (p = 0.004). For intra-observer variation, a reduction in contour variation
      was seen across all organs at risk in using motion compensated reconstructions.
      CONCLUSIONS: This work shows that there is benefit in using motion compensated
      reconstructions for reducing both inter-observer and intra-observer contouring
      variations for organs at risk in lung cancer patients.

PMID- 29221650
TI  - [Immunohistochemistry using clone VE1 is an economic, specific and sensitive
      method for detecting the presence of BRAFV600E mutations in melanoma].
AB  - BACKGROUND: Determination of BRAF mutation status is mandatory in the management
      of patients with inoperable stage IIIC or stage IV melanoma. Currently, molecular
      biology (MB) has been validated for detecting the presence of BRAF mutations.
      OBJECTIVE: To compare the sensitivity, specificity and cost of
      immunohistochemistry (IHC) (clone VE1) versus BM methods (qPCR and Sanger
      sequencing). PATIENTS AND METHODS: All the samples for which BRAF mutation status
      was requested between March 2013 and February 2015 at the cellular and molecular
      analysis laboratory of the Angers Hospital were included retrospectively and
      consecutively. The IHC (clone VE1) and BM analyses were performed with the same
      formalin-fixed paraffin embedded tumour samples. The cost of these two methods
      was determined on the basis of the cost for the French Health Insurance. RESULTS:
      Two hundred and seven samples were subjected to a determination of BRAF
      mutational status in IHC and BM. Only one sample was discordant between these two
      methods (positive in IHC, negative in BM). The sensitivity and specificity of the
      IHC was 100% and 99.25% respectively. The ratio of the cost of IHC/BM testing was
      1:2.1. CONCLUSION: IHC (clone VE1) is a specific, sensitive and economic method
      for determining BRAFV600E mutation status. Nevertheless, this method must be
      validated in order to be integrated into a decisional algorithm, alongside BM
      methods, to determine whether targeted BRAF-inhibitor therapy is indicated.

PMID- 29221651
TI  - [The myth of virgin cleansing: Latest news on an archaic magico-religious
      practice].
AB  - BACKGROUND: In the medical anthropology section of the Nanterre Hospital (France)
      for migrants and refugees, three cases were recorded of "virgin cleansing" in sub
      Saharan African countries. PATIENTS AND METHODS: These consisted of sexual
      assaults (2 instances of rape and 1 of sexual interference) on sexually immature
      females (young girls) by patients with sexually transmitted infections (mainly
      HIV, syphilis) hoping they might thereby be cured. DISCUSSION: These particularly
      atrocious hetero-aggressive sexual practices based on magical arguments are
      unfortunately universal and are not limited to a specific culture. At the medical
      anthropology level, the belief in cleansing by virgins is based on the notion
      that the patient is dirty and impure. In the same way that emetics and/or
      laxatives are prescribed in the case of intestinal disorders (to "eliminate" the
      disease), some subjects use diuretics for urinary abnormalities or, literally,
      "clean vaginas (or anuses)" to purge their own miasma. The rising tide of
      population migrations (some of whom carry chronic infections), refugee camps,
      prolonged incarcerations, etc., makes observations of such phenomena increasingly
      frequent. Belief in cleansing by virgins (and the fatal consequences thereof)
      will be difficult to eradicate. The education of populations and health
      professionals should promote absolute respect for the body of children, and, more
      generally, of others, particularly since at this time of increasingly marked
      migratory flows, this problem sadly risks becoming widespread.

PMID- 29221652
TI  - [Acyclovir-resistant perineal HSV infection revealing chronic lymphoid
      leukaemia].
AB  - BACKGROUND: Chronic HSV infection is a cause of chronic perineal ulcerations. We
      report a case of a chronic and refractory HSV infection revealing chronic
      lymphoid leukaemia. PATIENTS AND METHODS: An 85-year-old woman with an 8-month
      history of chronic perineal ulcerations was referred to our dermatology
      department. She had no previous medical history of herpes infection. Skin
      biopsies ruled out carcinoma but were consistent with HSV infection. A local swab
      was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir
      (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B
      chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of
      ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop).
      Foscarnet was administered for a period of 3 weeks with almost complete healing
      of the ulcerations. Treatment was stopped prematurely due to acute renal
      insufficiency and the remaining lesions were treated using imiquimod cream.
      Valaciclovir was prescribed to prevent further episodes. The condition recurred a
      mere 11 months later. DISCUSSION: The prevalence of ACV-resistant HSV is 0.32 %
      in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient
      dosing regimens or prolonged treatment with TK inhibitors result in the local
      selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase
      inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant
      HSV is less virulent and replicates less, with reactivations being mainly due to
      wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a
      preventive treatment. To our knowledge, this is the first case of ACV-resistant
      HSV infection revealing chronic lymphoid leukaemia. CONCLUSION: Chronic perineal
      ulcerations can be the first manifestation of immunodeficiency seen for example
      with haematological diseases. In the event of clinical resistance of an HSV
      infection to recommended thymidine kinase inhibitor regimens, the use of
      foscarnet should be considered.

PMID- 29221653
TI  - [Challenges posed by cosmetic skin-bleaching].

PMID- 29221654
TI  - Numerical simulation of hot-melt extrusion processes for amorphous solid
      dispersions using model-based melt viscosity.
AB  - Simulation of HME processes is a valuable tool for increased process
      understanding and ease of scale-up. However, the experimental determination of
      all required input parameters is tedious, namely the melt rheology of the
      amorphous solid dispersion (ASD) in question. Hence, a procedure to simplify the
      application of hot-melt extrusion (HME) simulation for forming amorphous solid
      dispersions (ASD) is presented. The commercial 1D simulation software Ludovic(r)
      was used to conduct (i) simulations using a full experimental data set of all
      input variables including melt rheology and (ii) simulations using model-based
      melt viscosity data based on the ASDs glass transition and the physical
      properties of polymeric matrix only. Both types of HME computation were further
      compared to experimental HME results. Variation in physical properties (e.g. heat
      capacity, density) and several process characteristics of HME (residence time
      distribution, energy consumption) among the simulations and experiments were
      evaluated. The model-based melt viscosity was calculated by using the glass
      transition temperature (Tg) of the investigated blend and the melt viscosity of
      the polymeric matrix by means of a Tg-viscosity correlation. The results of
      measured melt viscosity and model-based melt viscosity were similar with only few
      exceptions, leading to similar HME simulation outcomes. At the end, the
      experimental effort prior to HME simulation could be minimized and the procedure
      enables a good starting point for rational development of ASDs by means of HME.
      As model excipients, Vinylpyrrolidone-vinyl acetate copolymer (COP) in
      combination with various APIs (carbamazepine, dipyridamole, indomethacin, and
      ibuprofen) or polyethylene glycol (PEG 1500) as plasticizer were used to form the
      ASDs.

PMID- 29221655
TI  - Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma
      patients.
AB  - PURPOSE: Host response to polytrauma occasionally has unpredictable outcomes.
      Immune response is a major factor influencing patient's outcome. This study
      evaluated the interaction of two main cytokines in immune response after major
      trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma
      level of these cytokines is determined by mRNA expression of these cytokines
      genes which may decide the outcome of polytrauma patients. METHODS: This
      prospective multicenter trial held at four trauma centers enrolled 54 polytrauma
      patients [Injury Severity Score (ISS) >= 16]. Plasma levels and mRNA expression
      of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was
      conducted to observe whether patients endured multiple organ dysfunction syndrome
      (MODS) and death. MODS evaluation was performed using sequential organ failure
      assessment (SOFA). Trauma load which in this study is represented with ISS,
      plasma level, expression of cytokine genes and patient's outcome were examined
      with correlation test and statistical analysis. RESULTS: The elevated IL-6/IL-10
      ratio indicated increased activity of systemic inflammation response, especially
      pro-inflammation response which bears higher probability of progressing to MODS
      and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30)
      showed that compensatory anti-inflammation response syndrome (CARS) state was
      more dominant than systemic inflammatory response syndrome (SIRS), indicating
      that malfunction and failure of immune system eventually lead to MODS and deaths.
      The statistical significance in plasma level of cytokines was found in the
      outcome group which was defined as bearing a low trauma load but mortality.
      CONCLUSION: The pattern of cytokine levels in inflammation response has great
      impact on the outcome of polytrauma patients. Further study at the genetic level
      is needed to investigate inflammation process which may influence patient's
      outcome.

PMID- 29221656
TI  - Z-effect after intramedullary nailing systems for trochanteric femur fractures.
AB  - PURPOSE: The aim of this study was to investigate the incidence of Z-effect after
      dual lag screw intramedullary nailing systems and risk factors contributing to
      this effect. We hypothesized that long nails provide more neck strength due to a
      longer lever than short nails and are therefore less likely to develop a
      misbalance of a higher head compressive strength than neck compressive strength.
      METHODS: In this retrospective cohort study 103 patients treated operatively with
      a dual lag screw intramedullary nailing device for (sub)trochanteric hip fracture
      were included. We analysed patient charts regarding patient and operation
      characteristics. Furthermore we conducted radiologic measurements within the 2
      year follow-up period to investigate the quality of fracture fixation, implant
      failure and predictors for Z-effect. The re-operation risk was investigated with
      multivariate regression analysis. RESULTS: The incidence of (reversed) Z-effect
      in this study was 9% (n = 80); 6 out of 7 Z-effects occurred in the short nail
      group, which was not significant. Patients who were treated with a long nail had
      a significant larger number of complications in comparison with the short nail
      group (median 2 vs 0.5, p = 0.001). The long nail group received more often
      erythrocytes blood transfusions (82% vs 31%, p < 0.01) and had a longer hospital
      stay (13 vs 21 days, p < 0.05). Migration of lag screws (p <0.05) and unstable
      fracture type (p < 0.05), were risk factors for re-operation. The re-operation
      rate within 2 year after surgery was 21%, of which one fourth was due to a Z
      effect. CONCLUSION: The nail length was not associated with the development of a
      Z-effect. Migration of lag screws after intramedullary nailing is common and a
      risk factor for re-operation.

PMID- 29221657
TI  - Involvement of RNA helicase p68 in skin wound healing process in rats.
AB  - PURPOSE: RNA helicase p68 plays an important role in organ development and
      maturation through tuning cell proliferation. However, the character and role of
      p68 in the whole wound healing process need more study. METHODS: First, we
      characterize expression of p68 in normal rat skin development postnatal. Then, we
      assayed dynamic change of p68 in rat skin from different stage after injury, and
      explored the role of p68 in proliferation and migration of three types of wound
      healing related cells. RESULTS: p68 was down-regulated during skin developmental
      and maturation process, up-regulated after wound, peaked on day 14 and then
      significantly decreased. Wound fluid enhanced wound healing related cell
      proliferation and up-regulated expression of p68. Conversely, reducing p68
      expression by RNA interference resulted in significantly slower proliferation and
      migration. CONCLUSION: Our results define an important role of RNA helicase p68
      in skin wound healing process.

PMID- 29221658
TI  - GLP-1 receptor agonists: differentiation within the class.

PMID- 29221660
TI  - Re: Stromal Gene Expression is Predictive for Metastatic Primary Prostate Cancer.

PMID- 29221661
TI  - Re: Comprehensive Molecular Characterization of Muscle Invasive Bladder Cancer.

PMID- 29221659
TI  - Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in
      patients with type 2 diabetes: a meta-analysis.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective
      glucose-lowering drugs. Findings from cardiovascular outcome trials showed
      cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular
      efficacy were varied. We aimed to examine overall cardiovascular efficacy for
      lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS:
      In this systematic review and meta-analysis, we analysed data from eligible
      trials that assessed the safety and efficacy of GLP-1 receptor agonists compared
      with placebo in adult patients (aged 18 years or older) with type 2 diabetes and
      had a primary outcome including, but not limited to, cardiovascular mortality,
      non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and
      MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials.
      We did a meta-analysis of available trial data using a random-effects model to
      calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and
      odds ratios for key safety outcomes. FINDINGS: Of 12 articles identified in our
      search and screened for eligibility, four trials of cardiovascular outcomes of
      GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER
      (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide).
      Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10%
      relative risk reduction in the three-point major adverse cardiovascular event
      primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and
      non-fatal stroke; HR 0.90, 95% CI 0.82-0.99; p=0.033), a 13% RRR in
      cardiovascular mortality (0.87, 0.79-0.96; p=0.007), and a 12% relative risk
      reduction in all-cause mortality (0.88, 0.81-0.95; p=0.002), with low-to-moderate
      between-trial statistical heterogeneity. No significant effect of GLP-1 receptor
      agonists was identified on fatal and non-fatal myocardial infarction, fatal and
      non-fatal stroke, hospital admission for unstable angina, or hospital admission
      for heart failure. Overall, no significant differences were seen in severe
      hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer
      reported between GLP-1 receptor agonist treatment and placebo. INTERPRETATION:
      Our findings show cardiovascular safety across all GLP-1 receptor agonist
      cardiovascular outcome trials and suggest that drugs in this class can reduce
      three-point major adverse cardiovascular events, cardiovascular mortality, and
      all-cause mortality risk, albeit to varying degrees for individual drugs, without
      significant safety concerns. GLP-1 receptor agonists have a favourable risk
      benefit balance overall, which should allow the choice of drug to be
      individualised to each patient's needs. FUNDING: Amylin Pharmaceuticals
      (AstraZeneca).

PMID- 29221662
TI  - Rare presentation of the glomus tumor in the stomach.

PMID- 29221663
TI  - [Long-term outcomes of prostate cancer patients with lymph nodes metastasis after
      radical prostatectomy and pelvic lymph node dissection].
AB  - INTRODUCTION: The aim of this study was to evaluate biochemical recurrence-free
      survival (RFS) and to identify useful predictors of such survival in localized
      prostate cancer patients (cN0) and pelvic lymph node metastasis (pN+) treated
      with radical prostatectomy and pelvic lymph node dissection. PATIENTS AND
      METHODS: This multicenter and retrospective study, assessed overall survival
      (OS), cancer specific survival (CSS) and biochemical recurrence-free survival
      (RFS), between January 2005 until December 2010 with 5 years of distance. We
      evaluated factors predicting long-term RFS in node positive prostate cancer
      patients. RESULTS: Thus, 30 patients were included. Median follow-up was 89.9+/
      27.4 months. After surgery, patients were treated with surveillance (n=4, 13.5%),
      adjuvant hormone therapy (n=22, 73%) or combination of radio and hormone therapy,
      (n=4, 13.5%). During the follow-up, 50% of patients had biochemical recurrence,
      with a mean time period of 38+/-30 months. Five and 10-year RFS were 57% and 41%
      respectively. Extra lymph nodes extension (P=0.00021) and pathological margin
      status (P=0.0065) were independent predictors of 5-year RFS. CONCLUSION:
      Biochemical RFS of patients treated with radical prostatectomy and subclinical
      lymph node metastatic disease is adequate and multifactorial. However, this study
      identifies pathological margin status and extra lymph node extension as
      independent factors of b RFS. LEVEL OF EVIDENCE: 4.

PMID- 29221665
TI  - Effect of wrist posture, rate of force development/relaxation, and isotonic
      contractions on finger force independence.
AB  - The multi-articular anatomy and inter-connections of the extrinsic finger muscles
      suggests that wrist posture may affect enslaved finger forces. The purpose of
      this study was to determine the effects of (i) wrist posture on enslaved finger
      forces during ramp and isotonic exertions, and (ii) the rate of force development
      on enslaved forces and error. Twelve men performed 3 repetitions of isometric
      finger flexion and extension force with index and ring fingers with the wrist in
      30 degrees  flexion, neutral, and 30 degrees  extension. Trials consisted of an
      isotonic contraction at 25% of maximum, and two ramp contractions performed at
      25% MVC/s and 10% MVC/s up to 50% MVC, returning to zero at the same rate.
      Electromyography was recorded from compartments of extensor digitorum (ED) and
      flexor digitorum superficialis and analyzed at 25% MVC. Wrist posture
      significantly affected enslaving effect (EE) during extension exertions (F4, 44 >
      2.6, p < .05) with higher EE, error, and muscle activity of ED in wrist
      extension. Contraction condition significantly affected EE for index and ring
      finger exertions (p = .001). In fingers adjacent to the task finger, descending
      phase EE was higher than ascending phase, independent of muscle activity.
      Mechanical factors such as posture, and neural factors both contribute to
      enslaved finger actions.

PMID- 29221664
TI  - Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti
      Inflammatory Drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal
      tract, causing widespread morbidity and mortality. Although mechanisms of damage
      involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or
      cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review
      the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated
      and COX-independent processes. NSAIDs interact with phospholipids and uncouple
      mitochondrial oxidative phosphorylation, which initiates biochemical changes that
      impair function of the gastrointestinal barrier. The resulting increase in
      intestinal permeability leads to low-grade inflammation. NSAID inhibition of COX
      enzymes, along with luminal aggressors, results in erosions and ulcers, with
      potential complications of bleeding, protein loss, stricture formation, and
      perforation. We propose a model for NSAID-induced damage to the gastrointestinal
      tract that includes these complex, interacting, and inter-dependent factors. This
      model highlights the obstacles for the development of safer NSAIDs.

PMID- 29221666
TI  - Resumption of antiplatelet therapy in patients with primary intracranial
      haemorrhage: Balancing benefits and risks.

PMID- 29221667
TI  - Interleukin-27 and interleukin-37 are elevated in sickle cell anemia patients and
      inhibit in vitro secretion of interleukin-8 in neutrophils and monocytes.
AB  - BACKGROUND AND OBJECTIVE: Inflammation is implicated in the pathogenesis of most
      complications seen in sickle cell anemia (SCA) patients. We aimed to evaluate
      serum levels of two newly discovered anti-inflammatory cytokines (IL-27 and IL
      37), and pro-inflammatory cytokines among Brazilian SCA patients that are not on
      hydroxyurea therapy (HbSS), compared with hydroxyurea-treated patients (HbSSHU)
      and healthy controls (HbAA). Furthermore, we demonstrated the effect of IL-27, IL
      37, and heme on in vitro secretions of IL-8 in human neutrophils and monocytes.
      METHODS: A cross-sectional study of 82 consenting SCA (35 HbSS and 47 HbSSHU)
      patients in steady state and 49 HbAA consenting individuals. Clinical details
      were obtained from interviews and medical records. Serum levels of IL-27, IL-37,
      TGF-beta, TNF-alpha, IL-1beta, IL-6, and IL-8 were quantified by enzyme linked
      immunosorbent assay (ELISA). Neutrophils and monocytes were isolated from healthy
      controls, and cultured separately with or without cytokines (IL-27 and IL-37) and
      heme. Supernatant IL-8 concentration was determined by ELISA. RESULTS: Serum
      levels of IL-27, IL-37, IL-1beta, IL-6, and IL-8 were significantly elevated in
      HbSS patients compared to HbAA controls. Serum IL-8 levels were significantly
      higher in HbSS and HbSSHU patients than in controls. IL-27 and IL-37 were
      positively correlated in both HbSS and HbSSHU patients. In vitro IL-8 production
      by IL-27 and IL-37 pre-treated neutrophils and monocytes was significantly
      inhibited even after heme addition. CONCLUSIONS: Our findings show that IL-27 and
      IL-37, as well as the pro-inflammatory cytokines, are elevated in HbSS patients
      compared with controls, suggesting that the secretion of these anti-inflammatory
      cytokines is driven by the presence of pro-inflammatory cytokines. This role is
      probably sufficient in preventing further cellular or tissue damage but not
      potent enough to prevent inflammation. Therefore, IL-27 and IL-37 may be
      potential immuno-targets for ameliorating complications associated with elevated
      heme levels seen in SCA and other hemolytic anemias.

PMID- 29221668
TI  - Sumoylation of SMAD 4 ameliorates the oxidative stress-induced apoptosis in
      osteoblasts.
AB  - Oxidative stress-induced mitochondrial function and cell apoptosis to
      osteoblasts, plays a critical role in the pathophysiology of osteoporosis.
      However, mechanisms underlying such process remain not yet clear. We aims in this
      study to investigate a possible role of SMAD (the mothers against decapentaplegic
      homolog 4 (SMAD4) in the oxidative stress-induced apoptosis, in homo sapiens
      osteoblast hFOB1.19 cells. Results demonstrated that the treatment with more than
      100MUM H2O2 significantly downregulated the cellular viability, whereas markedly
      induced apoptosis in hFOB1.19 cells. The SMAD4 was markedly reduced in both mRNA
      and protein levels in the H2O2 -treated hFOB1.19 cells, along with the reduction
      of Small ubiquitin-related modifier 1 (SUMO 1) and SUMO 2/3. The
      immunoprecipitation assay confirmed indicated the interaction between SUMO 1 (or
      SUMO 2/3) and SMAD4. Moreover, the SMAD4 overexpression markedly ameliorated the
      H2O2-resulted viability reduction and apoptosis induction in hFOB1.19 cells.
      Interestingly, such amelioration was blocked by the knockdown of SUMO 2/3. Taken
      together, we conclued that SMAD4 inhibits the H2O2-induced apoptosis in
      osteoblast hFOB1.19 cells; such inhibition might depend on the SUMOylation by
      SUMO 2/3. It implies a promising role of SMAD4 in oxidative stress-promoted
      damage to osteoblasts.

PMID- 29221670
TI  - Sociodemographic and Obstetric Factors Related to Symptoms of Postpartum
      Depression in Hispanic Women in Rural California.
AB  - OBJECTIVE: To investigate the relationships among sociodemographic and obstetric
      factors and symptoms of postpartum depression (PPD) in Hispanic women living in
      rural California. DESIGN: Quantitative, cross-sectional, descriptive design.
      SETTING: Rural southern California communities. PARTICIPANTS: A convenience
      sample of 223 Hispanic women, ages 18 to 42 years old, with one living infant
      younger than 12 months old. METHODS: Interviewer-administered Edinburgh Postnatal
      Depression Scale and sociodemographic and obstetric history survey (maternal age,
      marital status, education, annual household income, employment, sex of infant,
      birth type, and number of children). Chi-square and logistic regression analyses
      were used to determine associations and predictive relationships among
      sociodemographic and obstetric factors and symptoms of PPD. RESULTS: Low
      education levels, unemployment, cesarean birth, and more than one young child
      were significantly related to PPD risk (Edinburgh Postnatal Depression Scale
      scores >= 10). Many of the factors associated with PPD symptoms in this sample of
      Hispanic women were similar to those previously reported in the literature.
      CONCLUSION: Our findings highlighted the need for PPD care among Hispanic women
      in rural areas. Early assessment and intervention for symptoms of PPD are needed
      to enhance health equity and promote better health for women who live in rural
      communities.

PMID- 29221671
TI  - Population-Based Risk Factors for Shoulder Dystocia.
AB  - OBJECTIVE: To re-examine the risk factors for shoulder dystocia given the
      increasing rates of obesity and diabetes in pregnant women. DESIGN: Retrospective
      observational study. SETTING: Five hospitals located in Wisconsin, Florida,
      Maryland, Michigan, and Alabama. PARTICIPANTS: We evaluated 19,236 births that
      occurred between April 1, 2011, and July 25, 2013. METHODS: Data were collected
      from electronic medical records and used to evaluate the risk of shoulder
      dystocia. Data were analyzed using a generalized linear mixed model, which
      controlled for clustering due to site. RESULTS: When insulin was prescribed,
      gestational diabetes was associated with an increased risk of shoulder dystocia
      (odds ratio = 2.10, 95% confidence interval [1.01, 4.37]); however, no similar
      association was found with regard to gestational diabetes treated with glycemic
      agents or through diet. Use of epidural anesthesia was associated with an
      increased risk for shoulder dystocia (odds ratio = 3.47, 95% confidence interval
      [2.72, 4.42]). Being Black or Hispanic, being covered by Medicaid or having no
      insurance, infant gestational age of 41 weeks or greater, and chronic diabetes
      were other significant risk factors. CONCLUSION: With the changing
      characteristics of pregnant women, labor and birth clinicians care for more
      pregnant women who have an increased risk for shoulder dystocia. Our findings may
      help prospectively identify women with the greatest risk.

PMID- 29221669
TI  - Regulation of pro- and anti-atherogenic cytokines.
AB  - Despite advances in prevention and treatment, vascular diseases continue to
      account for significant morbidity and mortality in the developed world. Incidence
      is expected to worsen as the number of patients with common co-morbidities linked
      with atherosclerotic vascular disease, such as obesity and diabetes, continues to
      increase, reaching epidemic proportions. Atherosclerosis is a lipid-driven
      vascular inflammatory disease involving multiple cell types in various stages of
      inflammation, activation, apoptosis, and necrosis. One commonality among these
      cell types is that they are activated and communicate with each other in a
      paracrine fashion via a complex network of cytokines. Cytokines mediate
      atherogenesis by stimulating expression of numerous proteins necessary for
      induction of a host of cellular responses, including inflammation, extravasation,
      proliferation, apoptosis, and matrix production. Cytokine expression is regulated
      by a number of transcriptional and post-transcriptional mechanisms. In this
      context, proteins that control and fine-tune cytokine expression can be
      considered key players in development of atherosclerosis and also represent
      targets for rational drug therapy to combat this disease. This review will
      describe the cellular and molecular mechanisms that drive atherosclerotic plaque
      progression and present key cytokines that participate in this process. We will
      also describe RNA binding proteins that mediate cytokine mRNA stability and
      regulate cytokine abundance. Identification and characterization of the cytokines
      and proteins that regulate their abundance are essential to our ability to
      identify therapeutic approaches to ameliorate atherosclerotic vascular disease.

PMID- 29221672
TI  - Cost and Use of Pasteurized Donor Human Milk at a Children's Hospital.
AB  - OBJECTIVE: To determine the cost and use of pasteurized donor human milk (PDHM)
      at a children's hospital with a strong human milk culture. DESIGN: A
      retrospective descriptive cohort study. SETTING: A children's hospital in the
      northeastern region of the United States. PARTICIPANTS: Infants (N = 281) younger
      than 1 year of age at the time of hospitalization who received PDHM between
      January 2011 and November 2014. Infants older than 1 year of age at the time of
      hospitalization were excluded from the study sample. METHODS: For each eligible
      infant, the following descriptive characteristics were abstracted from the
      electronic health record: gestational age, birth weight, primary diagnosis,
      unit/floor, total volume of PDHM fed to infant, total number of days the infant
      received PDHM, diet order on day of discharge, and total length of stay in days.
      Descriptive statistics were used to analyze all data. RESULTS: Of the sample, 70%
      (n = 197/281) were cared for in the NICU and 30% (n = 84/281) were cared for
      outside of the NICU. The mean number of days an infant received PDHM was 23 days
      (range = 1-134 days) and the mean volume consumed daily was 195 ml (range = 6
      1,335 ml). Using a purchase cost of U.S. $4.50 per ounce, the average purchase
      cost of PDHM per day was U.S. $29.19 (range = U.S. $0.90 to U.S. $200.23).
      CONCLUSION: PDHM is a low-cost intervention compared with many other
      interventions for the care of hospitalized infants.

PMID- 29221673
TI  - Mother doesn't always know best: Maternal wormlion choice of oviposition habitat
      does not match larval habitat choice.
AB  - Habitat choice is an important decision that influences animals' fitness. Insect
      larvae are less mobile than the adults. Consequently, the contribution of the
      maternal choice of habitat to the survival and development of the offspring is
      considered to be crucial. According to the "preference-performance hypothesis",
      ovipositing females are expected to choose habitats that will maximize the
      performance of their offspring. We tested this hypothesis in wormlions (Diptera:
      Vermileonidae), which are small sand-dwelling insects that dig pit-traps in sandy
      patches and ambush small arthropods. Larvae prefer relatively deep and obstacle
      free sand, and here we tested the habitat preference of the ovipositing female.
      In contrast to our expectation, ovipositing females showed no clear preference
      for either a deep sand or obstacle-free habitat, in contrast to the larval
      choice. This suboptimal female choice led to smaller pits being constructed later
      by the larvae, which may reduce prey capture success of the larvae. We offer
      several explanations for this apparently suboptimal female behavior, related
      either to maximizing maternal rather than offspring fitness, or to constraints on
      the female's behavior. Female's ovipositing habitat choice may have weaker
      negative consequences than expected for the offspring, as larvae can partially
      correct suboptimal maternal choice.

PMID- 29221675
TI  - Further study of the Montreal Cognitive Assessment's domain-specific metrics
      could allow for international data comparison and collaboration.

PMID- 29221674
TI  - The relationship between sweat chloride levels and mortality in cystic fibrosis
      varies by individual genotype.
AB  - RATIONALE: The association between CFTR genotype, sweat chloride and mortality
      has been inconsistent, but no previous analyses have examined the association
      stratified by individual genotypes. OBJECTIVES: To evaluate the genotype-specific
      association between sweat chloride and mortality. METHODS: The CFF Patient
      Registry was assessed and included all patients in the registry between 1996 and
      2012 with at least one F508del allele. We excluded patients without a documented
      genotype or plausible sweat chloride level. The primary outcome was time to
      mortality during the observation period. We examined 15 genotypes using the three
      most prevalent alleles in each of 5 classes. We compared subgroups of sweat
      chloride using Kaplan-Meier curves, log-rank tests, and multivariable Cox PH
      models. The overall predictive value of sweat chloride on mortality was assessed
      using area under the receiver operating characteristic curves. MEASUREMENTS AND
      MAIN RESULTS: 18,893 subjects met inclusion criteria. Sweat chloride distribution
      was similar across genotypes in patients with class 1 mutations, but was
      significantly different across genotypes in mutation classes 2-5. The
      R117H/F508del genotype patients demonstrated an association between sweat
      chloride and mortality (HR: 1.32 for every 10mmol/L increase in sweat chloride
      [95% CI 1.12-1.54]. There were also significant associations in patients with
      F508del/F508del, I507del/F508del, G551D/F508del and 2789+5G->A/F508del genotypes,
      though the clinical relevance for these genotypes is unclear. CONCLUSIONS: There
      is significant variability in sweat chloride distribution across CFTR class 2-5
      genotypes. The relationship between sweat chloride and mortality varies by
      genotype with a relatively strong relationship in R117H/F508del patients.

PMID- 29221676
TI  - Prospective medical analysis of radiation therapist image repositioning during
      image-guided radiotherapy.
AB  - PURPOSE: Radiation oncologists are responsible for deciding which day-to-day
      variations are acceptable or not in the treatment setup. However, properly
      qualified and trained radiation therapists might be capable to perform image
      registration. We evaluated in our centre the capability and accuracy of radiation
      therapists to validate positioning images in a prospective study. METHODS AND
      PATIENTS: A total of 84 patients treated for prostate, head and neck, lung or
      breast cancer was prospectively and randomly included from July 2011 to July 2013
      in radiotherapy unit of our institution. For each patient, three positioning
      images were randomly analysed. Two radiation oncologists analysed all positioning
      images and shifts decided by the radiation therapists in an independent and
      blinded way. The radiation oncologists had to decide whether to validate or not
      this shift and give a corresponding additional shift, if any. A theoretical
      disagreement rate less than 5% between radiation therapists and radiation
      oncologists was planned. RESULTS: A total of 240 images were analysed (head and
      neck: 15.0%; prostate: 14.2%; breast: 55.0%; lung: 15.8%). The global
      disagreement between radiation oncologists and radiation therapists for all the
      images analysed was 2.5% 95% confidence interval (95% CI) [1.0-5.0],
      corresponding to six images out of 240. A 100% agreement was reached for prostate
      and lung images, a 97.2% agreement for head and neck images and a 96.2% agreement
      for breast images. CONCLUSIONS: The radiation therapist validation for
      repositioning images seemed accurate for image-guided radiotherapy in our
      institution. Periodic evaluation and in-house training are warranted when routine
      delegation of image registration to radiation therapists is considered.

PMID- 29221677
TI  - Epigenetic Regulation of Biological Rhythms: An Evolutionary Ancient Molecular
      Timer.
AB  - Biological rhythms are pervasive in nature, yet our understanding of the
      molecular mechanisms that govern timing is far from complete. The rapidly
      emerging research focus on epigenetic plasticity has revealed a system that is
      highly dynamic and reversible. In this Opinion, I propose an epigenetic clock
      model that outlines how molecular modifications, such as DNA methylation, are
      integral components for timing endogenous biological rhythms. The hypothesis
      proposed is that an epigenetic clock serves to maintain the period of molecular
      rhythms via control over the phase of gene transcription and this timing
      mechanism resides in all cells, from unicellular to complex organisms. The model
      also provides a novel framework for the timing of epigenetic modifications during
      the lifespan and transgenerational inheritance of an organism.

PMID- 29221678
TI  - Hybrid imaging in foot and ankle disorders.
AB  - Disorders of the foot and ankle are some of the most frequent ones affecting the
      musculoskeletal system and have a great impact on patients' quality of life.
      Accurate diagnosis is an important clinical challenge because of the complex
      anatomy and function of the foot, that make it difficult to locate the source of
      the pain by routine clinical examination. In the study of foot pathology,
      anatomical imaging (radiography, magnetic resonance imaging [MRI], ultrasound and
      computed tomography [CT]) and functional imaging (bone scan, positron emission
      tomography [PET] and MRI) techniques have been used. Hybrid imaging combines the
      advantages of morphological and functional studies in a synergistic way, helping
      the clinician manage complex problems. In this article we delve into the anatomy
      and biomechanics of the foot and ankle and describe the potential indications for
      the current hybrid techniques available for the study of foot and ankle disease.

PMID- 29221679
TI  - The gnathobasic spine microstructure of recent and Silurian chelicerates and the
      Cambrian artiopodan Sidneyia: Functional and evolutionary implications.
AB  - Gnathobasic spines are located on the protopodal segments of the appendages of
      various euarthropod taxa, notably chelicerates. Although they are used to crush
      shells and masticate soft food items, the microstructure of these spines are
      relatively poorly known in both extant and extinct forms. Here we compare the
      gnathobasic spine microstructures of the Silurian eurypterid Eurypterus
      tetragonophthalmus from Estonia and the Cambrian artiopodan Sidneyiainexpectans
      from Canada with those of the Recent xiphosuran chelicerate Limulus polyphemus to
      infer potential variations in functional morphology through time. The thickened
      fibrous exocuticle in L. polyphemus spine tips enables effective prey mastication
      and shell crushing, while also reducing pressure on nerve endings that fill the
      spine cavities. The spine cuticle of E. tetragonophthalmus has a laminate
      structure and lacks the fibrous layers seen in L. polyphemus spines, suggesting
      that E. tetragonophthalmus may not have been capable of crushing thick shells,
      but a durophagous habit cannot be precluded. Conversely, the cuticle of S.
      inexpectans spines has a similar fibrous microstructure to L. polyphemus,
      suggesting that S. inexpectans was a competent shell crusher. This conclusion is
      consistent with specimens showing preserved gut contents containing various
      shelly fragments. The shape and arrangement of the gnathobasic spines is similar
      for both L. polyphemus and S. inexpectans, with stouter spines in the posterior
      cephalothoracic or trunk appendages, respectively. This differentiation indicates
      that crushing occurs posteriorly, while the gnathobases on anterior appendages
      continue mastication and push food towards and into the mouth. The results of
      recent phylogenetic analyses that considered both modern and fossil euarthropod
      clades show that xiphosurans and eurypterids are united as crown-group
      euchelicerates, with S. inexpectans placed within more basal artiopodan clades.
      These relationships suggest that gnathobases with thickened fibrous exocuticle,
      if not homoplasious, may be plesiomorphic for chelicerates and deeper relatives
      within Arachnomorpha. This study shows that the gnathobasic spine microstructure
      best adapted for durophagy has remained remarkably constant since the Cambrian.

PMID- 29221680
TI  - Paradorippe granulata - A crab with external fertilization and a novel type of
      sperm storage organ challenges prevalent ideas on the evolution of reproduction
      in Eubrachyura (Crustacea: Brachyura: Dorippidae).
AB  - Two fundamentally different sperm storage organs occur in Brachyura. The probably
      paraphyletic podotremes show intersegmental spermathecae, which are distant from
      oviducts and coxal gonopores. Hence, fertilization is external. In contrast to
      this, the seminal receptacles of Eubrachyura are directly connected with the
      ovaries. Thus, at least initial fertilization is internal. This pattern has been
      interpreted as an apomorphy of Eubrachyura. To test this hypothesis, we studied
      the morphology of the reproductive organs of Paradorippe granulata, a
      representative of the putatively early diverging eubrachyuran lineage
      Dorippoidea. Applying histology, 3D-reconstructions and micro-computed-tomography
      we revealed a novel type of sperm storage organ. Female P.granulata lack the
      characteristic eubrachyuran seminal receptacle. Instead sperm is stored in four
      cuticle-lined bursae, two on each side of the paired oviducts. The elaborate
      bulbous male gonopod with several terminal processes is adapted to transferring
      sperm into the female twin bursae. Since oviducts and twin bursae are not
      directly connected, spermatozoa and oocytes mix when gametes pass through the
      sternal vulva. Thus, fertilization in P.granulata is external. Our finding of a
      eubrachyuran crab that lacks seminal receptacles and exhibits external
      fertilization calls prevailing concepts on the evolution of sperm storage in
      Eubrachyura into question.

PMID- 29221681
TI  - Hypercalcemic crisis and primary hyperparathyroidism: Cause of an unusual
      electrical storm.
AB  - Hypercalcemia is a known cause of heart rhythm disorders, however its association
      with ventricular arrhythmias is rare. The authors present a case of a fifty-three
      years old male patient with a ischemic and ethanolic dilated cardiomyopathy, and
      severely reduced ejection fraction, carrier of cardiac resynchronization therapy
      (CRT) with cardioverter defibrillator (ICD), admitted in the emergency department
      with an electrical storm, with multiple appropriated ICD shocks, refractory to
      antiarrhythmic therapy. In the etiological investigation was documented severe
      hypercalcemia secondary to primary hyperparathyroidism undiagnosed until then.
      Only after the serum calcium level reduction ventricular tachycardia was stopped.

PMID- 29221682
TI  - Effects of fructose consumption on food intake and biochemical and body
      parameters in Wistar rats.
AB  - INTRODUTION AND OBJECTIVE: Increased fructose consumption is associated with
      various metabolic changes that favor the onset of obesity and related
      comorbidities. The objective of this study was to assess the effects of chronic
      fructose consumption on body weight and adipose tissue, as well as on serum
      glucose and triglyceride levels. METHODS: Thirty-day-old Wistar rats were divided
      into two groups: fructose (F) and control (C), which had free access to
      commercial chow and either water or a 20% fructose solution. Body mass was
      measured weekly and food consumption at 30, 60 and 90 days. At 90 days, the
      animals were killed by decapitation and fat deposits (mesenteric, epididymal and
      retroperitoneal) were removed and blood collected for measurement of glucose and
      triglyceride levels. RESULTS: There was no significant difference in body weight
      gain, but the percentage of body fat was higher in group F. This group also
      consumed less feed at 60 and 90 days and had higher consumption of fructose
      solution than water in group C at 30 and 60 days. This meant higher calorie
      intake in group F and lower feed efficiency. Retroperitoneal and epididymal fat
      deposits and triglycerides were higher in group F than in group C. CONCLUSION:
      Consumption of fructose solution for eight weeks, while not directly reflected in
      body weight gain, did increase abdominal fat in group F compared to group C, as
      well as changing triglyceride levels. These two factors increase risk of
      cardiovascular disease.

PMID- 29221683
TI  - The use of a 'pocket' printer to improve documentation and patient care.

PMID- 29221684
TI  - Ex-vivo flush of the limb allograft reduces inflammatory burden prior to
      transplantation.
AB  - BACKGROUND: Passenger leucocytes and inflammatory debris transferred from the
      donor limb to the recipient can induce allorecognition, which activates the host
      immune response. This is the first study to evaluate whether the transfer of this
      inflammatory burden can be reduced via post-preservation flush prior to
      revascularisation, and whether this is influenced by ischaemia. METHODS:
      Bilateral forelimbs from the same pig were procured and infused with preservation
      flush and stored on ice. Each limb from the same pig underwent a post
      preservation intravascular flush with isotonic solution at either 2 or 6 h.
      Venous effluent underwent flow cytometry to phenotype leucocyte populations, with
      additional quantification of cytokines and cell-free DNA. RESULTS: We identified
      large populations of viable leucocytes in the flush effluent (8.65 * 108 +/- 3.10
      * 108 cells at 2 h and 1.02 * 109 +/- 2.63 * 108 at 6 h). This comprised T cells,
      B cells, NK cells and monocytes. Post-preservation flush yielded significant
      concentrations of pro-inflammatory cytokines including IL-6, IL-18, GM-CSF, IL
      1beta, IL1alpha and CXCL-8 and mitochondrial DNA. The regulatory cytokine, IL-10
      was undetectable. CONCLUSIONS: This study supports the finding that a post
      preservation flush removes leucocytes and inflammatory components that are
      responsible for direct presentation. This study also gives an indication of how
      ischaemia impacts on the inflammatory burden transferred to the recipient upon
      reperfusion.

PMID- 29221685
TI  - Role of the Ceramide-CD300f Interaction in Gram-Negative Bacterial Skin
      Infections.

PMID- 29221686
TI  - Melanoma Tumor Characteristics: An Analysis of Mutational Burden and Copy Number
      Alterations by Patient Age and Stage.

PMID- 29221687
TI  - Leptomeningeal Carcinomatosis in Colorectal Cancer: The Mayo Clinic Experience.
AB  - BACKGROUND: Leptomeningeal metastasis (LM) is an uncommon form of metastatic
      disease in many cancers. There remains a paucity of literature with regard to the
      course and management of LM in colorectal cancers (CRCs). The aim of this study
      was to estimate the incidence of LM in patients with CRC seen at our institution
      over a 15-year period, and to describe the clinical course and outcome of these
      cases. METHODS: LM in CRC primary cases between 2000 and 2014 were identified in
      the Mayo Clinic databases. The charts were retrospectively reviewed. RESULTS: Of
      17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15-year
      period. Nine cases were included in the analysis. Four had metastatic disease at
      the time of their initial CRC diagnosis. Median overall survival after CRC
      diagnosis was 25.7 months (range, 4.7-74.8 months). Median time to diagnosis of
      LM after CRC diagnosis was 25.3 months (range, 0-68.1 months). All patients had
      magnetic resonance imaging findings consistent with LM: 3 patients with spinal
      LM, 5 patients with intracranial LM, and 1 with both. Neurologic symptoms
      correlated with site of the lesions, with headache, cranial nerve palsy, lower
      extremity weakness, and gait disturbance among the most frequently reported.
      However, not all patients had neurologic findings, with LM lesions found
      incidentally in 2 cases. Seven patients (78%) had palliative radiotherapy for LM.
      Three patients continued to receive systemic chemotherapy after diagnosis of LM.
      Median survival after LM diagnosis was 7 weeks (range, 2-39 weeks). CONCLUSIONS:
      LM is an exceedingly rare development in the natural course of CRC. It confers a
      poor prognosis with limited treatment options. At our institution, most patients
      had their disease addressed by palliative means, with many receiving radiotherapy
      to control their neurologic symptoms. Based on our series, supportive care
      remains a sensible approach to the management of LM in CRC.

PMID- 29221688
TI  - Primary Tumor Location and Survival in the General Population With Metastatic
      Colorectal Cancer.
AB  - BACKGROUND: Recent evidence from clinical trials suggests that primary tumor
      location in patients with metastatic colorectal cancer correlates with
      differential outcomes, and patients with tumors originating in the right side of
      the colon have inferior survival. We conducted a large population-based cohort
      study using individual patient data to confirm the prognostic importance of
      primary tumor location in the general population with metastatic colorectal
      cancer. METHODS: A cohort of 1947 patients who were diagnosed with metastatic
      colorectal cancer from 1992 to 2010 was studied. Ascending and transverse colon
      cancers were defined as right-sided tumors. Cox proportional multivariate
      analyses were done to determine prognostic significance of primary tumor
      location. RESULTS: The median age was 70 years (interquartile range, 60-78
      years), and the male to female ratio was 1.3:1. Twenty-nine percent had World
      Health Organization performance status of > 1. Seven-hundred and seventy (39%)
      patients had right-sided tumors, and 908 (47%) received chemotherapy. The median
      overall survival of patients with right-sided tumors was 14 months (95%
      confidence interval [CI], 12.7-15.3 months) compared with 20.5 months (95% CI,
      18.5-22.5 months) of patients with left-sided tumors (P < .001). On multivariate
      analysis, right-sided tumors (hazard ratio [HR], 1.40; 95% CI, 1.20-1.60), no
      metastasectomy (HR, 2.40; 95% CI, 1.90-2.90), intact primary tumor (HR, 1.60; 95%
      CI, 1.32-1.90), an elevated carcinoembryonic antigen level (HR, 1.54; 95% CI,
      1.30-1.90), lack of combination chemotherapy (HR, 1.52; 95% CI, 1.31-1.80), stage
      IVb disease (HR, 1.50; 95% CI, 1.17-1.86), leukocytosis (HR, 1.44; 95% CI, 1.28
      1.73), and World Health Organization performance status > 1 (HR, 1.30; 95% CI,
      1.10-1.55) were correlated with inferior survival. CONCLUSIONS: Our results
      confirm that individuals with metastatic colorectal cancer and right-sided tumors
      who received chemotherapy have inferior survival independent of other known
      prognostic variables. Future studies are required to understand the underlying
      pathophysiology.

PMID- 29221689
TI  - Tissue regeneration: The crosstalk between mesenchymal stem cells and immune
      response.
AB  - Mesenchymal stem cells (MSCs) exist in almost all tissues with the capability to
      differentiate into several different cell types and hold great promise in tissue
      repairs in a cell replacement manner. The study of the bidirectional regulation
      between MSCs and immune response has ushered an age of rethinking of tissue
      regeneration in the process of stem cell-based tissue repairs. By sensing damaged
      signals, both endogenous and exogenous MSCs migrate to the damaged site where
      they involve in the reconstitution of the immune microenvironment and empower
      tissue stem/progenitor cells and other resident cells, whereby facilitate tissue
      repairs. This MSC-based therapeutic manner is conferred as cell empowerment. In
      this process, MSCs have been found to exert extensive immunosuppression on both
      innate and adaptive immune response, while such regulation needs to be licensed
      by inflammation. More importantly, the immunoregulation of MSCs is highly
      plastic, especially in the context of pathological microenvironment.
      Understanding the immunoregulatory properties of MSCs is necessary for
      appropriate application of MSCs. Here we review the current studies on the
      crosstalk of MSCs and immune response in disease pathogenesis and therapy.

PMID- 29221690
TI  - Inflammatory cells implicated in neoplasia development in idiopathic inflammatory
      bowel disease.
AB  - The inflammatory mechanisms that lead to the clinical symptoms that are grouped
      under the term inflammatory bowel disease have not been fully characterized.
      Although a specific mechanism has not been identified, inflammatory bowel disease
      is believed to be related to an inability by the immune system to shut active
      inflammation within the intestine. Many contributing factors have been implicated
      in the disease process. Based on population studies, patients with inflammatory
      bowel disease have an increased risk for neoplastic development. Although no
      specific immune cell has been implicated in neoplastic development within this
      patient population, several immune cells have been implicated as possible
      etiologies in inflammatory bowel disease. In this review, we will review the
      clinical evidence about the risk for neoplastic development in inflammatory bowel
      disease and the current clinical guidelines to survey this patient population. We
      will also review the pathologic assessment of inflammation within this patient
      population as well the underlying immune cells and cytokines that have been
      implicated in the etiology of inflammatory bowel disease.

PMID- 29221691
TI  - Characteristics and Outcomes of Pediatric Heart Failure-Related Emergency
      Department Visits in the United States: A Population-Based Study.
AB  - OBJECTIVES: To describe the frequency, characteristics, and outcomes of heart
      failure-related emergency department (ED) visits in pediatric patients. We aimed
      to test the hypothesis that these visits are associated with higher admission
      rates, mortality, and resource utilization. STUDY DESIGN: A retrospective
      analysis of the Nationwide Emergency Department Sample for 2010 of patients <=18
      years of age was performed to describe ED visits with and without heart failure.
      Cases were identified using International Classification of Disease, Ninth
      Revision, Clinical Modification codes and assessed for factors associated with
      admission, mortality, and resource utilization. RESULTS: Among 28.6 million
      pediatric visits to the ED, there were 5971 (0.02%) heart failure-related cases.
      Heart failure-related ED patients were significantly more likely to be admitted
      (59.8% vs 4.01%; OR 35.3, 95% CI 31.5-39.7). Among heart failure-related visits,
      admission was more common in patients with congenital heart disease (OR 5.0, 95%
      CI 3.3-7.4) and in those with comorbidities including respiratory failure (OR
      78.3, 95% CI 10.4-591) and renal failure (OR 7.9, 95% CI 1.7-36.3). Heart failure
      related cases admitted to the hospital had a higher likelihood of death than
      nonheart failure-related cases (5.9% vs 0.32%, P < .001). Factors associated with
      mortality included respiratory failure (OR 4.5, 95% CI 2.2-9.2) and renal failure
      (OR 7.8, 95% CI 2.9-20.7). Heart failure-related ED visits were more expensive
      than nonheart failure-related ED visits ($1460 [IQR $861-2038] vs $778 [IQR $442
      1375] [P < .01].) CONCLUSIONS: Heart failure-related visits represent a minority
      of pediatric ED visits but are associated with increased hospital admission and
      resource utilization.

PMID- 29221692
TI  - Reply.

PMID- 29221693
TI  - Development of Late Circadian Preference: Sleep Timing From Childhood to Late
      Adolescence.
AB  - OBJECTIVES: To assess differences relating to circadian preference in objectively
      measured sleep patterns from childhood to adolescence over a 9-year period. We
      hypothesized there is developmental continuity in sleep timing and duration
      according to circadian preference. STUDY DESIGN: Young participants (N = 111, 65%
      girls) from a community-based birth cohort underwent sleep actigraphy at mean
      ages 8.1 (SD = 0.3), 12.3 (SD = 0.5), and 16.9 (SD = 0.1) years. A short version
      of Morningness-Eveningness Questionnaire was administered in late adolescence. At
      each follow-up, sleep midpoint, duration, wake after sleep onset, sleep
      efficiency, and weekend catch-up sleep were compared between those reporting
      morning, intermediate, and evening preferences in late adolescence. RESULTS:
      Mixed model analyses indicated that sleep timing was significantly earlier among
      morning types compared with evening types at all ages (P values < .04). The mean
      differences in sleep midpoint between morning and evening types increased from a
      mean of 19 minutes (age 8), 36 minutes (age 12), to 89 minutes (age 17). The
      largest change occurred from age 12 to 17 years. Sleep duration, wake after sleep
      onset, sleep efficiency, and catch-up sleep did not differ according to circadian
      preference. CONCLUSIONS: This study found significant continuity in sleep timing
      from childhood to adolescence over 9 years, indicating that late circadian
      preference reported in late adolescence begins to manifest in middle childhood.
      Further studies are needed to establish whether sleep timing has its origins at
      an even earlier age.

PMID- 29221694
TI  - PHACE Syndrome-before and after Propranolol Therapy.

PMID- 29221696
TI  - Fertility Preservation in Pediatric Subspecialties: A Pilot Needs Assessment
      Beyond Oncology.
AB  - Physicians from 6 non-oncology pediatric subspecialties were surveyed about
      fertility preservation (FP) to assess education/service needs. Almost all (96%;
      25 of 26) reported having patients at risk of infertility; however, only 58% (15
      of 26) had discussed FP with patients' families. Most subspecialists (92%; 23 of
      25) would like access to an FP program. Our data support exploring the expansion
      of FP programs beyond oncology.

PMID- 29221695
TI  - Sleep-Disordered Breathing among Newborns with Myelomeningocele.
AB  - In a matched cohort study, we report that the apnea-hypopnea index is
      significantly higher in neonates with myelomeningocele (34 +/- 22) compared with
      age-matched controls (19 +/- 11; P = .021). Assessment of newborns with
      myelomeningocele for sleep-disordered breathing may facilitate early treatment;
      the impact on long-term neurodevelopment is unknown.

PMID- 29221697
TI  - Prevalence of Mental Health Disorders in Elderly U.S. Military Veterans: A Meta
      Analysis and Systematic Review.
AB  - OBJECTIVE: Older veterans may be vulnerable to mental health problems. Meta
      analytic and systematic review methods sought to determine the prevalence rate of
      mental health disorders in older military veterans (>=65 years). METHODS: Eleven
      studies were eligible, and meta-analyses of veteran depression, substance abuse,
      post-traumatic stress disorder (PTSD), anxiety, dementia, bipolar disorder, and
      schizophrenia were conducted. RESULTS: Although conducted exclusively with U.S.
      veterans, high prevalence rates of substance (5.7%) and alcohol use disorders
      (5.4%) in older veterans were found. However, the prevalence of other mental
      health disorders, including PTSD and depression, in older veterans was not
      markedly high. CONCLUSION: The rates of disorder prevalence observed indicates a
      need for continued awareness of mental health difficulties, particularly
      substance and alcohol use disorders, in older veterans. In the future studies
      with non-U.S. military samples using a longitudinal design are required to
      further understand the prevalence of mental health disorders in geriatric
      veterans.

PMID- 29221698
TI  - Undulating Clinical Course of Noncompaction Cardiomyopathy.

PMID- 29221699
TI  - Selection of the Best of 2017 in Ischemic Heart Disease.

PMID- 29221700
TI  - Acute and Long-term Results After Contemporary Subcutaneous Implantable
      Cardioverter-defibrillator Implantation: A Single-center Experience.
AB  - INTRODUCTION AND OBJECTIVES: The subcutaneous implantable cardioverter
      defibrillator (S-ICD) has emerged as an alternative to the transvenous
      defibrillator. The incidence of complications is similar, with inappropriate
      shocks (IS) being more frequent than those occurring with contemporary
      programming of transvenous defibrillators. Several improvements have been
      implemented after the S-ICD was approved for use in Europe in 2009. This study
      reports the results of S-ICD use in a single center, whose experience began late,
      at the end of 2013. METHODS: Prospective observational study including
      consecutive patients with defibrillator indication and no indication for either
      permanent pacing or cardiac resynchronization who underwent S-ICD implantation.
      Implant data and long-term follow-up were analyzed. RESULTS: An S-ICD was
      implanted in 50 patients who were deemed suitable after electrocardiographic
      screening. The mean age was 46.9+/-15 (range, 15-78) years and 72% were male.
      Thirty eight percent had left ventricular ejection fraction <= 35%. The most
      frequent heart disease was ischemic heart disease (34%), followed by hypertrophic
      cardiomyopathy (18%). The intermuscular technique was used, with 3 incisions in
      10% and 2 incisions in the remaining 90%. Ventricular fibrillation was induced in
      49 patients, with 100% effectiveness in their conversion. After a mean follow-up
      of 18.1 (range, 2.3-44.8) months, there were no late complications requiring
      surgical revision, the rate of IS was 0%, and 1 patient (2%) experienced
      appropriate shocks. CONCLUSIONS: Improvements in technology, implant technique
      and device programming, along with appropriate patient selection, have led to
      outstanding acute and long-term results, especially regarding the absence of both
      IS and complications requiring surgical revision.

PMID- 29221701
TI  - Isolation of bastadin-6-O-sulfate and expedient purifications of bastadins-4, -5
      and -6 from extracts of Ianthella basta.
AB  - Bastadin-6-34-O-sulfate ester (8) was isolated from methanol extracts of
      Ianthella basta. The structure of 8 was characterized by analysis of MS and NMR
      data, and conversion through acid hydrolysis, to the parent compound, bastadin-6,
      which was identical by HPLC, MS and NMR with an authentic sample. An improved
      procedure for procurement of pure samples of bastadins-4 (4), -5 (5) and -6 (6)
      is described.

PMID- 29221702
TI  - Screening plant derived dietary phenolic compounds for bioactivity related to
      cardiovascular disease.
AB  - The potential health benefits of phenolic acids found in food and beverages has
      been suggested from a number of large population studies. However, the mechanism
      of how these compounds may exert biological effects is less well established. It
      is also now recognised that many complex polyphenols in the diet are metabolised
      to simple phenolic acids which can be taken up in the circulation. In this paper
      a number of selected phenolic compounds have been tested for their bioactivity in
      two cell culture models. The expression and activity of endothelial nitric oxide
      synthase (eNOS) in human aortic endothelial cells and the uptake of glucose in
      muscle cells. Our data indicate that while none of the compounds tested had a
      significant effect on eNOS expression or activation in endothelial cells, several
      of the compounds increased glucose uptake in muscle cells. These compounds also
      enhanced the translocation of the glucose transporter GLUT4 to the plasma
      membrane, which may explain the observed increase in cellular glucose uptake.
      These results indicate that simple cell culture models may be useful to help
      understand the bioactivity of phenolic compounds in relation to cardiovascular
      protection.

PMID- 29221703
TI  - Four new compounds from the roots of Euphorbia ebracteolata and their inhibitory
      effect on LPS-induced NO production.
AB  - Three new diterpenoids, ebractenoids O~Q (1-3), and a new phenolic glucoside,
      gamma-pyrone-3-O-beta-d-(6-galloyl)-glucopyranoside (4), together with 6 known
      compounds, were isolated from the 95% ethanol extract of the roots of Euphorbia
      ebracteolata, and their structures were elucidated on the basis of spectroscopic
      data. The absolute configurations of 1-3 were determined by electronic circular
      dichroism (ECD) calculations. The inhibitory effects of all the isolates with
      exception of compounds 8 and 10 on the NO production in lipopolysaccharide (LPS)
      induced macrophages were evaluated. All of them exhibited significant inhibitory
      activity.

PMID- 29221704
TI  - Tremulane sesquiterpenes from cultures of the basidiomycete Irpex lacteus.
AB  - Five new tremulane sesquiterpenes, named irlactins F-J (1-5), were isolated from
      cultures of the basidiomycete Irpex lacteus together with two known analogues (6
      and 7). Structures and relative configurations of compounds 1-5 were elucidated
      by spectroscopic data analysis. Compund 4 exhibited moderate cytotoxicities on HL
      60, SMMC-7721, A-549, MCF-7, and SW480 cells with IC50 values of 16.23, 20.40,
      25.55, 19.05, and 18.58MUM, respectively.

PMID- 29221705
TI  - Female fertility preservation in the pediatric and adolescent cancer patient
      population.
AB  - The 5-year survival rate for childhood cancer is over 80%, thereby increasing the
      number of young women facing infertility in the future because of the gonadotoxic
      effects of chemotherapy and radiation. The gonadotoxic effects of childhood
      cancer treatment vary by the radiation regimen and the chemotherapeutic drugs
      utilized. Although the American Society of Clinical Oncology guidelines recommend
      fertility preservation for all patients, there are several barriers and ethical
      considerations to fertility preservation in the pediatric and adolescent female
      population. Additionally, the fertility preservation methods for pre- and
      postpubertal females differ, with only experimental methods available for
      prepubertal females. We will review the risk of chemotherapy and radiation on
      female fertility, the approach to fertility preservation in the pediatric and
      adolescent female population, methods of fertility preservation for both pre- and
      postpubertal females, barriers to fertility preservation, cost, and psychological
      and ethical considerations.

PMID- 29221706
TI  - Rapid profiling method for mammalian feces short chain fatty acids by GC-MS.
AB  - Short chain fatty acids (SCFAs) are key feces metabolites generated by gut
      bacteria fermentation. Despite the importance of profiling feces SCFAs, technical
      difficulties in analysis remain due to their volatility and hydrophilicity. We
      improve previous protocols to profile SCFAs and optimize the metabolite profiling
      platform for mammalian feces samples. In this study, we investigated feces as
      biological samples using gas chromatography-mass spectrometry (GC-MS). Isobutyl
      chloroformate was used for a derivatization in aqueous solution without drying
      out the samples. Ultimately, we envisage being able to determine the way in which
      gut bacteria fermentation influences host gut condition by using our rapid
      metabolite profiling methods.

PMID- 29221707
TI  - Development of a borreliosis assay: Mannan coated polyethylene sinter bodies as a
      new platform technology.
AB  - Rapid diagnosis of Lyme borreliosis has been carried out on chemically modified
      porous polyethylene sinter bodies. Photografting of 2-propenol on sinter body's
      surface was performed as a first step, introducing active hydroxyl groups as a
      result of polyalcohol formation. The hydroxyl groups were used for further
      immobilization and could be linked via 3-aminopropyltriethoxysilane (APTES) to
      polysaccharides like mannan. Prone to coupling, mannan was activated using N, N'
      disuccinimidyl carbonate (DSC) to allow smooth reaction with the primary amine
      groups of the silane layer. In a final preparation step, a recombinant fusion
      protein consisting of the mannan-binding domain of the lectin Concanavalin A
      (ConA) and a specific Borrelia surface antigen was immobilized by self
      organization on the mannan surface. The fusion protein was used as biological
      interface structure. This strategy is highly efficient and resulted in a defined
      orientation of the antigen part of the fusion protein. Rapid and convenient
      differentiation could be then established between Borrelia-negative and a 
      positive serum even in 1000-fold diluted samples and detection of Lyme
      borreliosis in a rather early stage is likely. Furthermore, this generic strategy
      can be easily transferred to other bacterial or viral antigen structures.

PMID- 29221708
TI  - Daily versus monthly disposable contact lens: Which is better for ocular surface
      physiology and comfort?
AB  - PURPOSE: To investigate the effect of soft contact lenses (SCL) wearing modality
      and lens materials on the changes in conjunctival bulbar and limbal redness and
      conjunctival and corneal staining after two months of SCL wear. Comfort level was
      also analyzed. METHODS: In this longitudinal clinical trial, forty-seven neophyte
      myopic subjects were fitted with a monthly disposable lens (lotrafilcon-B or
      comfilcon-A or balafilcon-A) in one eye and a daily disposable lens (nelfilcon-A
      or stenofilcon-A or nesofilcon-A) in the other eye, randomly selected.
      Conjunctival bulbar and limbal redness and conjunctival and corneal staining were
      evaluated before and after lens wear. Effect of lens wearing modality and lens
      materials on these changes was also determined. Level of comfort was evaluated
      subjectively twice per day. Comfort level and reduction in end-of-day comfort
      were compared between different lens wearing modalities and materials. RESULTS:
      Bulbar and limbal redness and conjunctival and corneal staining were increased
      (p<0.001) after lens wear, and changes were similar with daily and monthly
      disposable lens wear (p>0.05). Limbal redness was associated with lens materials,
      and lotrafilcon-B induced the least among the studied lenses (p<0.05). There was
      no significant association between the wearing modality and the average comfort
      level and reduction of end-of-day comfort (p>0.05). CONCLUSION: Two months of SCL
      wear increased conjunctival redness, conjunctival and corneal staining, which
      were not associated with the lens wearing modality. There was a reduction in end
      of-day comfort, similar to daily and monthly lenses. The change in limbal redness
      and reduction in end-of-day comfort were associated with the characteristics of
      the lens material.

PMID- 29221709
TI  - The use of contact lenses among university students in Chengdu: Knowledge and
      practice of contact lens wearers.
AB  - PURPOSE: To assess the prevalence and general knowledge of contact lens wearers
      among college students in Chengdu, a metroplolitan of Chinaand find out the
      routine habits of use and hygienic conditions when wearing contact lenses.
      METHOD: The questionnaire was distributed to 1,600 ametropic participants who
      were from 8 different universities. Data about demographics, general contact lens
      handling habits, personal attitudes, hygiene behaviors and eye health conditions
      were collected. We made the analysis ofthe demographics and wearing of contact
      lenses. Possible reasons for behaviors related to the care of contact lenses were
      analyzed. RESULTS: The prevalence of contact lens use was 19.80%. Most users
      (82.15%) were females. An aesthetic effect was cited as the first reason for
      using (57.91%). The comfort of eyes was the first consideration (75.76%) when
      buying. To keep clean and use safe, 86.20% subjects washed hands before handling
      and 83.50% cleaned the lens carefully after removing. There was significant
      difference between males and females regarding the replacement of the solution
      (p=0.014). 32.66% wears knew the removal of protein deposits. A total of 54.88%
      were not informed of the potential complications of contact lens. The incidence
      of ocular discomfort was 44.78%. Only 3.03% of the students paid regular visits
      to ophthalmic clinics. CONCLUSION: The prevalence of contact lenses was
      relatively low in Chengdu. The wears had limited knowledge about using and careof
      contact lens. More education on standard lens wear and care should be provided to
      wearers.

PMID- 29221710
TI  - Acanthamoeba keratitis in patients wearing scleral contact lenses.
AB  - PURPOSE: To report a series of cases of Acanthamoeba keratitis (AK) in scleral
      lens wearers with keratoconus to determine whether this type of contact lens
      presents a greater risk for development of infection. METHODS: This study reports
      three patients who wore scleral contact lenses to correct keratoconus and
      developed AK. The diagnoses of AK were established based on cultures of the
      cornea, scleral contact lenses, and contact lens paraphernalia. This study
      investigated the risk factors for infections. RESULTS: The possible risks for AK
      in scleral contact lens wearers are hypoxic changes in the corneal epithelium
      because of the large diameter and minimal tear exchange, use of large amounts of
      saline solution necessary for scleral lens fitting, storing the scleral lens
      overnight in saline solution rather than contact lens multipurpose solutions, not
      rubbing the contact lens during cleaning, and the space between the cornea and
      the back surface of the scleral lens that might serve as a fluid reservoir and
      environment for Acanthamoeba multiplication. Two patients responded well to
      medical treatment of AK; one is still being treated. CONCLUSIONS: The
      recommendations for use and care of scleral contact lenses should be emphasized,
      especially regarding use of sterile saline (preferably single use), attention to
      rubbing the lens during cleaning, cleaning of the plunger, and overnight storage
      in fresh contact lens multipurpose solutions without topping off the lens
      solution in the case.

PMID- 29221711
TI  - Sitosterol prevents obesity-related chronic inflammation.
AB  - The physiological roles of phytosterols in chronic inflammation, which are
      believed to be involved in the underlying mechanisms for metabolic diseases, have
      yet to be elucidated. Therefore, in the present study, we aimed to elucidate the
      physiological roles of phytosterols in both clinical studies and animal
      experiments. We observed the existence of rather specific negative correlations
      between the serum sitosterol level and the serum IL-6 and the TNF-alpha levels in
      both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple
      regression analyses also revealed that the serum IL-6 and TNF-alpha levels
      exhibited strong negative correlations with the serum sitosterol levels. When
      ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8
      hetero mice were fed a high-fat diet, we observed that the increase in body
      weight, the fatty liver changes, and the expansion of perigonadal adipose tissues
      were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also
      observed that the plasma IL-6 and TNF-alpha levels, the expressions of TNF-alpha
      and PAI-1 in the liver and the expressions of the IL-6, TNF-alpha, and MCP-1
      levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest
      that sitosterol might suppress obesity-related chronic inflammation and might be
      applicable to the treatment of metabolic diseases.

PMID- 29221712
TI  - Modulating allergic response by engineering the major Parietaria allergens.

PMID- 29221713
TI  - Effect of grass sublingual tablet immunotherapy is similar in children and
      adults: A Bayesian approach to design pediatric sublingual immunotherapy trials.
AB  - BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT)
      trials because of inherent data variability secondary to inconsistent allergen
      exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging,
      but a Bayesian approach using prior adult data can reduce the necessary sample
      size. OBJECTIVE: We sought to describe how a Bayesian framework using prior
      information from adult trials can be used to improve pediatric SLIT clinical
      development. METHODS: Data were compiled by using a frequentist approach
      (conventional clinical trial approach independent of prior data) from trials
      conducted during the clinical development of timothy grass SLIT-tablets. RESULTS:
      The treatment effect of timothy grass SLIT-tablets was considered similar between
      pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined
      symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to
      30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific
      IgG4 and IgE-blocking factor increased from baseline in both children and adults
      treated with timothy grass SLIT-tablets. Given the reasonable assumption in
      similarity of treatment response between adults and children, a Bayesian approach
      is described to demonstrate rigorous efficacy criteria for pediatric trials
      incorporating information from prior adult trials and thereby reduce the sample
      size. CONCLUSIONS: Data support the similarity of efficacy and immunologic
      changes between children and adults treated with SLIT for allergic
      rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to
      design feasible trials in children, which might reduce unsafe off-label use by
      promoting more quickly proper labeling of approved products.

PMID- 29221714
TI  - Changes in regulatory B-cell levels in bone marrow, blood, and sputum of patients
      with asthma following inhaled allergen challenge.

PMID- 29221715
TI  - Corrigendum to "Aiding risk information learning through simulated experience
      (ARISE): Using simulated outcomes to improve understanding of conditional
      probabilities in prenatal Down syndrome screening" [Patient Educ. Counselling 100
      (October (10)) (2017) 1882-1889].

PMID- 29221716
TI  - CRISPR-Based Gene Drives for Pest Control.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene
      drives (GDs) could be used to spread desirable genetic elements through wild
      populations. With the imminent development of this technology in vertebrates, we
      believe that it is timely to highlight two forms of sex-ratio distorting GDs that
      show potential as pest management tools.

PMID- 29221717
TI  - Effect of metformin combined with lifestyle modification versus lifestyle
      modification alone on proinflammatory-oxidative status in drug-naive pre-diabetic
      and diabetic patients: A randomized controlled study.
AB  - BACKGROUND: Targeting biomarkers of oxidative-proinflammatory stress may result
      in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk
      factors and subsequent risk reduction. METHODS: 64 newly diagnosed
      antihyperglycemic treatment-naive prediabetic and type 2 diabetes mellitus (T2DM)
      patients were randomly assigned using block design to either metformin combined
      with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI),
      waist circumference, blood pressure, fasting plasma glucose (FPG), glycated
      hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor
      necrosis factor (TNF)-alpha were measured at baseline, after 3 months and after 6
      months from baseline. RESULTS: Except for HbA1c, baseline values did not differ
      significantly between the two groups. The post 3-months relative reductions in
      BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention
      were significantly greater than those in TLC alone group. TNFalpha plasma levels
      were decreased significantly vs. baseline by metformin combined with TLC
      intervention (-22.90+/-46.76%, P=0.01). Conversely, TLC alone basically worsened
      proinflammatory status (42.40+/-40.82 %), P<0.001. Metformin with TLC treatment
      effected a therapeutic decrement of the oxidative stress (-15.44+/-35.32%,
      P=0.029 vs. baseline) unlike TLC alone (61.49+/-122.66%, P=0.01 vs. baseline).
      Both interventions' effects were sustained in the 6-month follow up periods.
      CONCLUSION: In both intervention groups, the relative changes in plasma TNFalpha
      were significantly correlated (P<0.01) with systolic blood pressure and the
      relative changes in oxidative stress were markedly correlated (P<0.05) with total
      cholesterol.

PMID- 29221718
TI  - Correlation between dual-energy spectral CT imaging parameters and pathological
      grades of non-small cell lung cancer.
AB  - AIM: To investigate the correlation between pathological grades of non-small cell
      lung cancers (NSCLCs) and quantitative parameters generated in dual-energy
      spectral computed tomography (CT). MATERIALS AND METHODS: Fifty-three patients
      with NSCLCs who underwent preoperative dual-energy spectral CT imaging and
      surgical resection were evaluated retrospectively. These patients were divided
      into a low-grade group and a high-grade group based on their histopathological
      differentiation. In the arterial phase (AP) and venous phase (VP), iodine
      concentration (IC) in cancers was measured in iodine-based material decomposition
      images, and normalised to the IC in the aorta to calculate the normalised iodine
      concentration (NIC), the spectral CT curve was generated from the monochromatic
      images to calculate the slope of the spectral curve (lambdaHU). Differences in
      quantitative parameters (NIC and lambdaHU) were compared using the two-sample t
      test. The correlations between spectral CT parameters and tumour grades were
      evaluated using the Spearman rank correlation analysis. Receiver operating
      characteristic (ROC) curves were generated to calculate their diagnostic
      efficacies. RESULTS: The NIC and lambdaHU in the low-grade NSCLC group were
      significantly higher than those in the high-grade NSCLC group both in AP and VP
      (all p<0.001). There was a significant negative correlation between spectral CT
      parameters and pathological grades by the Spearman rank correlation (all
      p<0.001). ROC analysis indicated that lambdaHU in VP provided the best diagnostic
      performance in distinguishing high-grade cancers from low-grade cancers (area
      under the ROC curve [AUC], 0.914; sensitivity, 85.7%; specificity, 84.4%).
      CONCLUSION: The quantitative parameters in dual-energy spectral CT imaging
      provide useful information to differentiate the pathological grades of NSCLCs.

PMID- 29221719
TI  - Integration of different criteria for borderline resectable pancreatic cancer
      using classification tree analysis: the use of radiological tumour-vascular
      interface in correlation with surgical and pathological outcomes.
AB  - AIM: To integrate various criteria for borderline resectable pancreatic cancer
      (BRPC) based on radiological parameters using classification tree analysis.
      MATERIALS AND METHODS: The institutional review board approved this retrospective
      study and waived the requirement for informed consent. Two hundred and thirty
      five tumour-vein interfaces and 67 tumour-artery interfaces in 245 patients with
      surgically confirmed pancreatic ductal adenocarcinoma who underwent both
      preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were
      assessed by two independent readers. Radiological parameters for evaluation of
      the tumour-vascular interface were boundary, length of interface, degree of
      circumferential interface, and contour deformity of affected vessels.
      Classification tree analysis was performed to determine parameters associated
      with vascular invasion using pathological and surgical results as the reference
      standard. RESULTS: In the classification tree analysis for the tumour-vein
      interface, contour deformity and degree of circumferential interface were the
      first and second determining factors, respectively, for both surgical and
      pathological vascular invasion. For the tumour-artery interface, boundary and
      degree of circumferential interface were the first and second determining factors
      for surgical invasion, while contour deformity and length of interface were the
      first and second determining factors for pathological invasion. The BRPC group of
      modified criteria arbitrarily formed based on the results had similar surgical
      (74.1-81.6%) and pathological (54.3-63.3%) venous invasion compared to that of
      the National Comprehensive Cancer Network (NCCN) criteria, and the lowest
      surgical (33.3%) and pathological (6.7%) arterial invasion compared with those in
      previously established criteria for BRPC (43.3-55.6% and 22.2-26.1%,
      respectively). CONCLUSION: Various criteria for BRPCs were integrated using
      classification tree analysis, and a modified criterion for BRPC, which provides
      satisfactory results, was established.

PMID- 29221720
TI  - Strategy of endovascular treatment for renal artery aneurysms.

PMID- 29221721
TI  - Factors affecting the precision of lesion sizing with contrast-enhanced spectral
      mammography.
AB  - AIM: To evaluate the precision of the pre-surgical measurement of the size of
      breast cancer by contrast-enhanced spectral mammography (CESM). MATERIAL AND
      METHODS: This was a retrospective study of 204 breast cancers. Variables related
      to tumour biology and anthropometric variables were recorded and considered when
      evaluating the efficacy of CESM in predicting tumour size. Microscopic
      measurement of the largest diameter of the tumour at pathology was chosen as the
      reference standard. RESULTS: The mean size of tumours at pathology was 20.7+/
      15.8 mm, while at CESM it was 23.6+/-16.7 mm (Bland-Altman 2.9 mm overestimation,
      2.9 mm; 95% confidence interval [CI]: -10.3-16.2 mm). Spearman's correlation
      coefficient was 0.83 (p<0.0001). The concordance analysis indicated that 37.8% of
      the measurements were concordant, 47% were overestimated, and 15.2% were
      underestimated. Tumour size, nodal involvement, breast density, and breast size
      significantly modified the sizing accuracy. CONCLUSION: Quality of tumour size
      prediction with CESM is good, and this appears to be a promising imaging
      technique in the surgical planning of breast cancer. Biological tumour features,
      and anthropological characteristics of the patients do, however, affect the
      diagnostic precision and should be taken into account.

PMID- 29221722
TI  - Ink-enhanced dermoscopy is a useful tool to differentiate acquired solitary
      plaque porokeratosis from other scaly lesions.

PMID- 29221723
TI  - Effects of thyroxine on expression of proteins related to thyroid hormone
      functions (TR-alpha, TR-beta, RXR and ERK1/2) in uterus during peri-implantation
      period.
AB  - INTRODUCTION: Thyroid hormone is known to play important role during embryo
      implantation, however mechanisms underlying its actions in uterus during peri
      implantation period has not been fully identified. In this study, we hypothesized
      that thyroid hormone could affect expression of proteins related to its function,
      where these could explain mechanisms for its action in uterus during this period.
      METHODS: Female rats, once rendered hypothyroid via oral administration of
      methimazole (0.03% in drinking water) for twenty-one days were mated with fertile
      euthyroid male rats at 1:1 ratio. Pregnancy was confirmed by the presence of
      vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80
      MUg/kg/day) was then subcutaneously administered to pregnant, hypothyroid female
      rats for three days. A day after last injection (day four pregnancy), female rats
      were sacrificed and expression of thyroid hormone receptors (TR-alpha and beta),
      retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in
      uterus were quantified by Western blotting while their distribution in
      endometrium was visualized by immunofluorescence. RESULTS: Expression of TRalpha
      1, TRbeta-1 and ERK1/2 proteins in uterus increased with increasing doses of
      thyroxine however no changes in RXR expression was observed. These proteins were
      found in the stroma with their distribution levels were relatively higher
      following thyroxine treatment. CONCLUSIONS: Increased expression of TRalpha-1,
      TRbeta-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant
      rats indicate the importance of thyroxine in up-regulating expression of these
      proteins that could help mediate the uterine changes prior to embryo
      implantation.

PMID- 29221724
TI  - Downregulation of KLK13 promotes the invasiveness and metastasis of oesophageal
      squamous cell carcinoma.
AB  - KLK13 downregulation occurs in tumour tissues in comparison with adjacent normal
      tissues from patients with oesophageal squamous cell carcinoma (OSCC). KLK13 mRNA
      levels were tested in OSCC tumour tissues and adjacent noncancerous tissues from
      138 patients. In addition, the correlation between KLK13 mRNA levels and OSCC
      clinicopathologic features was analysed. KLK13 mRNA levels decreased notably in
      tumour tissues compared with those in adjacent noncancerous tissues. And
      decreased KLK13 mRNA levels indicated significant correlations with higher tumour
      grade, elevated TNM (UICC, 2009) stage classification, deeper infiltration and
      more lymph node metastases. And thus KLK13 may be a promising diagnostic marker.
      Decreased KLK13 mRNA levels also correlate with poor survival, which indicates
      that KLK13 mRNA expression may be a potential prognostic marker, although it
      could not be an independent prognostic factor by multivariate analysis. In vitro
      experiments of the OSCC cell lines KYSE150 and KYSE450 demonstrated that
      overexpression of KLK13 inhibits cell invasion and migration. Thus, KLK13 is a
      unique novel molecule useful for monitoring OSCC progression. Full elucidation of
      the role of KLK13 in OSCC may reveal avenues for investigating the molecule's
      functional potential as a novel therapeutic drug for targeting OSCC.

PMID- 29221725
TI  - Protective effects of polyphenol-rich infusions from carob (Ceratonia siliqua)
      leaves and cladodes of Opuntia ficus-indica against inflammation associated with
      diet-induced obesity and DSS-induced colitis in Swiss mice.
AB  - In the present study, we have investigated the effects of polyphenol-rich
      infusions from carob leaves and OFI-cladodes on inflammation associated with
      obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss
      mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI
      cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6,
      TNF-alpha and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated
      RAW 264.7 cells concomitant with NF-kappabeta nucleus translocation inhibition.
      For in vivo investigations, Swiss male mice were subjected to control or high fat
      diet (HFD). At the 8th week after the start of study, animals received or not 1%
      infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to
      2% DSS administration in drinking water over last 7 days. After sacrifice, pro
      inflammatory cytokines levels in plasma and their mRNA expression in different
      organs were determined. Results showed that carob leaf and OFI-cladode infusions
      reduced inflammation severity associated with HFD-induced obesity and DSS-induced
      acute colitis indicated by decrease in pro-inflammatory cytokines expression (as
      such TNF-alpha, IL1b and IL-6) in colon, adipose tissue and spleen. In addition,
      plasma levels of IL-6 and TNF-alpha were also curtailed in response to infusions
      treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal
      permeability through the restoration of tight junction proteins (Zo1, occludins)
      and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and
      OFI-cladodes could be attributed to their polyphenols which might alleviate
      inflammation severity associated with obesity and colitis.

PMID- 29221727
TI  - Epigenetic mechanisms in developmental neurotoxicity.
AB  - The constant interplay between environment (including both exogenous and
      endogenous factors) and epigenome (defined as the combination of chromatin, its
      covalent modifications and noncoding RNAs) triggers epigenetic events that, by
      modulating gene expression, capture information about changes in the environment.
      In this mini review, we will focus on the neurodevelopmental implications of
      exposure to adverse prenatal milieu with emphasis on mechanistic and functional
      aspects. Several neurotoxic insults have been shown to affect epigenetics with
      negative consequences on the development of the nervous system; among them are
      methylmercury, lead, arsenic and cadmium, as well as excess of glucocorticoids.
      Further investigations on the individual susceptibility to epigenetic changes are
      needed to propose and validate such modifications as possible biomarkers for
      early identification of neurological/neurodevelopmental disorders and for
      predicting/monitoring response to treatment.

PMID- 29221726
TI  - miRNA-495 suppresses proliferation and migration of colorectal cancer cells by
      targeting FAM83D.
AB  - microRNAs (miRNAs) have been reported to play crucial roles in malignant tumor
      progression, including cell development, proliferation, and progression.
      Increasing evidence suggests that miR-495 functions as either an oncogene or
      tumor suppressor in several tumor types. However, its biological role in the
      development of colorectal cancer (CRC) still remains unclear. In this study, we
      found that miR-495 expression level was remarkably down-regulated in CRC tissues
      samples and cell lines when compared to adjacent normal tissues and cell line by
      using qRT-PCR detection. Ectopic expression of miR-495 by mimic transfection
      significantly suppressed CRC cell proliferation and colony formation, inhibited
      migration and invasion, and induced apoptosis according to CCK-8, colony
      formation, transwell, and flow cytometry assays. Furthermore, bioinformatics and
      luciferase reporter assays verified that family with sequence similarity 83,
      member D (FAM83D) was a direct target of miR-495 in CRC cells, and FAM83D was
      confirmed to be upregulated in human CRC tissues and reversely correlated with
      miR-495 expression. In addition, rescue experiments revealed that restoration of
      FAM84D could partially abrogate the inhibitory effect of miR-495 overexpression
      on CRC cell proliferation and metastasis. Further mechanic investigations also
      verified that the PTEN/P13K/AKT/mTOR pathway was involved in the miR-495/FAM83D
      mediated CRC cell progression. Our findings identified that miR-495 acted as a
      critical tumor suppressor by directly targeting FAM83D during CRC development and
      therefore represented as a potential biomarker for CRC therapy.

PMID- 29221728
TI  - Emulsified isoflurane induces release of cytochrome C in human neuroblastoma SHSY
      5Y cells via JNK (c-Jun N-terminal kinases) signaling pathway.
AB  - A large number of studies have demonstrated that inhalation anesthetic isoflurane
      induced neural cell death by apoptosis in various cell and animal models.
      Emulsified isoflurane (EIso) is a new type of intravenous preparation of
      isoflurane that attracts increasing research attention as a promising clinical
      agent due to its both advantages as an intravenous and inhalation anesthetics
      medication. However, its safety and underlying molecular mechanism of
      neurotoxicity largely remain unknown. Therefore, it is meaningful to investigate
      the safety of EIso and to further elucidate its mechanism of anesthetic
      neurotoxicity. Human neuroblastoma SHSY-5Y cells were cultured, followed by a
      random exposure to one of three doses of EIso (0.56mmol/l, 1.12mmol/l, and
      2.24mmol/l) or the corresponding intralipid as vehicle (0.3956MUl/ml,
      0.7912MUl/ml and 1.5824MUl/ml) for 6h, 12h or 24h. Cell viability was evaluated
      by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay and
      the morphological changes were determined by a light microscope. We detect JNK, p
      JNK and cytochrome C (cyto C) protein levels by western blotting. SP600125, a
      specific inhibitor of JNK, was used to detect the role of JNK pathway in the
      neurotoxicity of EIso. Our study showed that EIso reduced the viability of SHSY
      5Y cells in a dose- and time-dependent manner. 0.56mmol/l EIso has no significant
      effects on cell viability, while 1.12mmol/l of EIso with 24-h and 2.24mmol/l of
      EIso with over 12-h exposure notably reduced cell viability. EIso dramatically
      increased the levels of p-JNK and cyto C. The JNK pathway inhibitor SP600125
      significantly increased the cell viability of SHSY-5Y cells induced by EIso.
      These findings suggest that EIso induces damage in human neuroblastoma SHSY-5Y
      cells by JNK signaling pathway activation and cyto C release. SP600125 protects
      neural cells against EIso-induced injury. Our findings provide a new insight in
      the exploration of potential novel therapeutic strategies for the treatment of
      EIso-induced neurotoxicity and other neurodegenerative diseases.

PMID- 29221729
TI  - High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals
      Interindividual Variation and Tissue Specialization.
AB  - Given the limited efficacy of clinical approaches that rely on ex vivo generated
      dendritic cells (DCs), it is imperative to design strategies that harness
      specialized DC subsets in situ. This requires delineating the expression of
      surface markers by DC subsets among individuals and tissues. Here, we performed a
      multiparametric phenotypic characterization and unbiased analysis of human DC
      subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported
      phenotypic heterogeneity of human cDC2s among individuals, including variable
      expression of functional receptors such as CD172a. We found marked differences in
      DC subsets localized in blood and lymphoid tissues versus skin, and a striking
      absence of the newly discovered Axl+ DCs in the skin. Finally, we evaluated the
      capacity of anti-receptor monoclonal antibodies to deliver vaccine components to
      skin DC subsets. These results offer a promising path for developing DC subset
      specific immunotherapies that cannot be provided by transcriptomic analysis
      alone.

PMID- 29221732
TI  - Poor responders after bariatric surgery - Are there second chances?

PMID- 29221730
TI  - Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving
      Allogenic CD4+ T Cell Dysfunction.
AB  - CD4+ T cells orchestrate immune responses and destruction of allogeneic organ
      transplants, but how this process is regulated on a transcriptional level remains
      unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a
      key transcriptional determinant controlling T cell responses during
      transplantation. IRF4 deletion in mice resulted in progressive establishment of
      CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4
      repressed PD-1, Helios, and other molecules associated with T cell dysfunction.
      In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis
      regulatory elements were increased, resulting in enhanced PD-1 expression and
      CD4+ T cell dysfunction. The dysfunctional state of Irf4-deficient T cells was
      initially reversible by PD-1 ligand blockade, but it progressively developed into
      an irreversible state. Hence, IRF4 controls a core regulatory circuit of CD4+ T
      cell dysfunction, and targeting IRF4 represents a potential therapeutic strategy
      for achieving transplant acceptance.

PMID- 29221734
TI  - Aortic annulus does not dilate over time after aortic root remodeling with or
      without annuloplasty.
AB  - OBJECTIVE: The lack of annular stabilization is the drawback of aortic root
      remodeling, and recently the addition of annuloplasty has been proposed. Limited
      data, however, exist on late annular size after remodeling. We studied annular
      size over time. METHODS: In 241 patients (53 +/- 16 years) annular size was
      determined preoperatively (T0), before discharge (T1), and at least 2 years after
      remodeling (T2, 54 +/- 27 months) with (n = 52) or without external suture
      annuloplasty. Seventeen patients had Marfan syndrome (7%), 100 a bicuspid valve
      (41%), and 22 acute dissection (9%). Mean graft size was 25.2 +/- 1.3 mm, and
      annuloplasty size 24.3 +/- 1.4 mm. RESULTS: Annular size was significantly
      reduced after repair and remained stable over time (T0: 27.4 +/- 3.0 mm, T1: 24.2
      +/- 2.5 mm, T2: 24.2 +/- 2.6 mm). After propensity-score matching (n = 33 each),
      baseline annular size was similar (with annuloplasty vs without: 28.7 +/- 4.1 mm
      vs 27.8 +/- 2.8 mm). Annular reduction was less effective without annuloplasty
      (23.9 +/- 2.0 mm vs 25.6 +/- 2.2 mm, P < .01); size was identical at follow-up
      (23.8 +/- 2.2 mm vs 25.1 +/- 2.5 mm, P = .03). After matching, freedom from
      annular size increase >10% at 4 years was 93 +/- 5% without annuloplasty and 91
      +/- 9% with annuloplasty (P = .92). A linear mixed-effects model identified no
      significant effect of annuloplasty on annulus diameter change at T2 (P = .48).
      Era after 2004, Marfan syndrome, and smaller annulus diameter at discharge were
      the independent predictors for late annular expansion. CONCLUSIONS: Aortic
      annulus rarely dilates over time after remodeling. In the case of annular
      dilatation, annuloplasty normalizes annular size and may prevent further
      dilatation by enhancing cusp coaptation. Even without annuloplasty, the aortic
      annulus becomes smaller compared with preoperative dimensions when aortic valve
      remains competent.

PMID- 29221733
TI  - Diagnostic performance of commercial serological assays measuring Bordetella
      pertussis IgG antibodies.
AB  - Due to their specificity to B. pertussis antigens, immunoglobulin G (IgG)
      antibodies should be measured primarily for diagnosing pertussis. We compared the
      diagnostic performance of commercially available enzyme-linked immunosorbent
      assays (ELISAs) and chemiluminescent immunoassays (CLIAs) measuring IgG to B.
      pertussis antigens. An in-house ELISA with purified pertussis toxin (PT) was used
      as reference system. Commercial assays using PT only as coating antigen showed
      better performance as compared to those using a mixture of different antigens.
      The best diagnostic performances were achieved by CLIAs. Results were analyzed
      using a dual cutoff of either >=125IU/mL anti-PT IgG or >=62IU/mL anti-PT IgG for
      the in-house ELISA and accordingly to package inserts for commercial assays.
      Using the in-house ELISA at a 62 IU/mL cutoff, as the gold standard for
      interpretation of results from the commercial kits, resulted in lower sensitivity
      and higher specificity as compared to 125IU/mL, thus, it may be especially useful
      in outbreak situations when high specificity is required.

PMID- 29221731
TI  - White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective
      Memory Responses to Infection.
AB  - White adipose tissue bridges body organs and plays a fundamental role in host
      metabolism. To what extent adipose tissue also contributes to immune surveillance
      and long-term protective defense remains largely unknown. Here, we have shown
      that at steady state, white adipose tissue contained abundant memory lymphocyte
      populations. After infection, white adipose tissue accumulated large numbers of
      pathogen-specific memory T cells, including tissue-resident cells. Memory T cells
      in white adipose tissue expressed a distinct metabolic profile, and white adipose
      tissue from previously infected mice was sufficient to protect uninfected mice
      from lethal pathogen challenge. Induction of recall responses within white
      adipose tissue was associated with the collapse of lipid metabolism in favor of
      antimicrobial responses. Our results suggest that white adipose tissue represents
      a memory T cell reservoir that provides potent and rapid effector memory
      responses, positioning this compartment as a potential major contributor to
      immunological memory.

PMID- 29221735
TI  - Comparison of digital and traditional thoracic drainage systems for postoperative
      chest tube management after pulmonary resection: A prospective randomized trial.
AB  - OBJECTIVE: The objective of this study was to evaluate whether a digital thoracic
      drainage system (group D) is clinically useful compared with a traditional
      thoracic drainage system (group T) in chest tube management following anatomic
      lung resection. METHODS: Patients scheduled to undergo segmentectomy or lobectomy
      were prospectively randomized before surgery to group D or T. A stratification
      randomization was performed according to the following air leak risk factors:
      age, sex, smoking status, and presence of emphysema and/or chronic obstructive
      pulmonary disease. The primary end point was the duration of chest tube
      placement. RESULTS: No statistically significant differences were found between
      groups D (n = 135) and T (n = 164) with regard to the duration of chest tube
      placement (median, 2.0 vs 3.0 days; P = .149), duration of hospitalization
      (median, 6.0 vs 7.0 days; P = .548), or frequency of postoperative adverse events
      (25.1% vs 20.7%; P = .361). In subgroup analyses of the 64 patients with
      postoperative air leak (20 in group D and 44 in group T), the duration of chest
      tube placement (median, 4.5 vs 4.0 days; P = .225) and duration of postoperative
      air leak (median, 3.0 vs 3.0 days; P = .226) were not significantly different
      between subgroups. CONCLUSIONS: The use of a digital thoracic drainage system did
      not shorten the duration of chest tube placement in comparison to a traditional
      thoracic drainage system after anatomic lung resection.

PMID- 29221736
TI  - Differential effects of operative complications on survival after surgery for
      primary lung cancer.
AB  - OBJECTIVE: Complications adversely affect survival after lung cancer surgery. We
      tested the hypothesis that effects of complications after lung cancer surgery on
      survival vary substantially across the spectrum of postoperative complications.
      METHODS: The Society of Thoracic Surgeons General Thoracic Surgery Database was
      linked to Medicare data for lung cancer resections from 2002 through 2013.
      Linkage was achieved for 29,899 patients. A survival model was created that
      included operative complications as explanatory variables and adjusted for
      relevant baseline covariates. Because of violation of the proportional hazard
      assumption, we used time-varying coefficient Cox modeling for the complication
      variables. RESULTS: Median patient age was 73 years, and 48% were male.
      Procedures performed were lobectomy in 69%, wedge in 17%, segmentectomy in 7%,
      bilobectomy in 3%, pneumonectomy in 3%, and sleeve lobectomy in 1%. Most frequent
      complications were atrial arrhythmia (14%), pneumonia (4.3%), reintubation
      (3.8%), delirium (2%), and acute kidney injury (1.4%). In the early period (0-90
      days), 12 complications are associated with worse survival. From 3 to 18 months
      after surgery, only 4 complications are associated with survival: delirium, blood
      transfusion, reintubation, and pneumonia. After 18 months, only sepsis and blood
      transfusion are associated with a significant late hazard. CONCLUSIONS: Our
      analysis confirmed the presence of differential magnitude and time-varying
      effects on survival of individual complications after lung cancer surgery. We
      conclude that the derived time-dependent hazard ratios can serve as objective
      weights in future models that enhance performance measurement and focus attention
      on prevention and management of complications with greatest effects.

PMID- 29221738
TI  - Discussion.

PMID- 29221737
TI  - If airlines can do it, we can too....

PMID- 29221739
TI  - Providing cardiothoracic services in 2035: Signs of trouble ahead.
AB  - OBJECTIVE: As the population ages, we will present the reality around being able
      to meet the health care needs of our population. In particular, we will present
      that providing cardiothoracic services in 2035 with a shortage of surgeons and an
      unknown caseload may be an impossibility. METHODS: By using data from the
      American Board of Thoracic Surgery, we estimate that in 2010, 4000 cardiothoracic
      surgeons performed more than 530,000 cases. Additionally, cardiothoracic
      residency programs train and certify on average 90 new surgeons every year. To
      estimate the number of cases for 2035, we consulted the Census Bureau figures for
      2010 and population projections for 2035. We then estimated the expected caseload
      for cardiothoracic surgeons relative to heart surgery, as well as lung and
      esophageal surgery. We found that among 2010 cardiothoracic surgeons in the
      United States, they completed more than 530,000 cases. RESULTS: We project that
      by 2035 there will be 853,912 cases to perform, representing an increase from
      2010 to 2035 of approximately 61% nationally. The cases per surgeon, per year, in
      2010 averaged 135 for almost each of the 4000 surgeons. In 2035, the average
      caseload per surgeon will be 299 cases, representing an increase of 121% for the
      individual surgeon. CONCLUSIONS: We conclude that by 2035, cardiothoracic
      surgeons will be responsible for more than 850,000 patients requiring surgery.
      This represents a 61% increase in the national case load and a potential for a
      121% increase for each cardiothoracic surgeon. We believe this is not feasible
      and a sign of trouble ahead.

PMID- 29221740
TI  - Discussion.

PMID- 29221741
TI  - Balloon-expandable transaortic transcatheter aortic valve implantation with or
      without predilation.
AB  - OBJECTIVE: It has been reported that balloon aortic valvuloplasty immediately
      before transfemoral or transapical transcatheter aortic valve implantation has
      mostly little to no clinical value. We aimed to provide data on the need for
      balloon aortic valvuloplasty in patients undergoing transaortic transcatheter
      aortic valve implantation. METHODS: Patients undergoing transaortic transcatheter
      aortic valve implantation with the Edwards SAPIEN XT (Nyon, Switzerland) or 3
      transcatheter heart valve were prospectively included at 18 sites across Europe.
      In the present analysis, we compare the periprocedural and 30-day outcomes of
      patients undergoing conventional (+ balloon aortic valvuloplasty) versus direct (
      balloon aortic valvuloplasty) transaortic transcatheter aortic valve
      implantation. RESULTS: Of the 300 patients enrolled, 222 underwent conventional
      and 78 underwent direct transaortic transcatheter aortic valve implantation. Peak
      and mean transvalvular gradients were improved in both groups with no significant
      difference between groups. Procedural duration, contrast agent volume, and
      requirement for postdilation were also comparable. A trend toward fewer
      periprocedural complications was evident in the direct group (3.9% vs 11.3%; P =
      .053), with significantly lower rates of permanent pacemaker implantation (0% vs
      5.0%; P = .034). Balloon aortic valvuloplasty omission had no significant effect
      on any of the 30-day safety and efficacy outcomes, including Valve Academic
      Research Consortium-2 composite end points (early safety events: 22.7% vs 17.4%,
      odds ratio, 1.17, 95% confidence interval, 0.53-2.62; clinical efficacy events:
      20.5% vs 18.7%, odds ratio, 1.14, 95% confidence interval, 0.51-2.55).
      CONCLUSIONS: For many patients, balloon aortic valvuloplasty predilation seems to
      have little clinical value in transaortic transcatheter aortic valve implantation
      using a balloon expandable transcatheter valve and may result in a higher rate of
      periprocedural complications, particularly in terms of permanent pacemaker
      implantation.

PMID- 29221742
TI  - Early experience with robotic mitral valve repair with intra-aortic occlusion.
AB  - OBJECTIVE: To report the learning curve and early results of robotic mitral valve
      repairs in comparison with propensity score-matched sternotomy controls after the
      adoption of a robotic mitral valve surgery program in a university teaching
      hospital. METHODS: A total of 142 patients underwent robotic mitral valve repair
      due to degenerative mitral regurgitation between May 2011 and December 2015.
      Control patients operated on via the conventional sternotomy approach were
      selected by the use of propensity score analysis resulting in 2 well-matched
      study groups. RESULTS: Valve repair rate was 98.6% and 97.9% in the robotic and
      sternotomy groups, respectively. Operation length, cardiopulmonary bypass, aortic
      crossclamp, and ventilation times were shorter in the sternotomy group. All of
      these times were statistically significantly reduced within the robotic group
      during the learning curve. Even though there was no statistically significant
      difference in the rate of perioperative complications between the groups, 3
      patients in the robotic group required postoperative extracorporeal membrane
      oxygenation due to low cardiac output, and 1 patient in the robotic group died.
      In the robotic and sternotomy groups, 86.3% versus 84.7% of patients had grade
      <=1+ mitral valve regurgitation at the latest follow-up visit, and there was no
      statistically significant difference in survival or reoperation rate between the
      2 study groups during follow-up. CONCLUSIONS: The present series reports the
      entire early learning curve related to the introduction of robotic mitral valve
      repair in our institution. In all, repair rate and early durability were
      acceptable, but more patients in the robotic group had serious complications.
      Early major robotic complications that occurred may have been related to the
      simultaneous use of intra-aortic occlusion.

PMID- 29221743
TI  - Ex vivo hydrodynamics after central and paracommissural edge-to-edge technique: A
      further step toward transcatheter tricuspid repair?
AB  - OBJECTIVES: Transcatheter approaches in heart valve disease became tremendously
      important and are currently established in the aortic position, but transcatheter
      tricuspid repair is still in its beginning and remains challenging. Replicating
      the surgical edge-to-edge technique, for example, with the MitraClip System
      (Abbott Vascular, Santa Clara, Calif), represents a promising option and has been
      reported successfully in small numbers of cases. However, up to now, few data
      considering the edge-to-edge technique as a transcatheter approach are available.
      This study aims to determine the ex vivo hydrodynamics after the central and
      paracommissural edge-to-edge technique in different pathologies. METHODS: Because
      of basal or apical dislocation of papillary muscles, leaflet prolapse or
      tethering was simulated in porcine tricuspid valves mounted on a flexible holding
      device. Central and paracommissural edge-to-edge techniques were evaluated
      successively in these pathologies. Regurgitant volume and mean transvalvular
      gradient were determined in a pulse duplicator. RESULTS: In this ex vivo model,
      the isolated edge-to-edge technique reduced tricuspid regurgitation. In the
      prolapse model, regurgitant volume decreased significantly after central edge-to
      edge technique (from 49.4 +/- 13.6 mL/stroke to 39.3 +/- 14.1 mL/stroke). In the
      tethering model, both the central and the paracommissural edge-to-edge techniques
      led to a significant decrease (from 48.7 +/- 13.9 to 43.6 +/- 15.6 and to 41.1 +/
      13.8 mL/stroke). In all cases, the reduction of regurgitant volume was achieved
      at the cost of significantly increased mean transvalvular gradient. CONCLUSIONS:
      This study provides a reduction of tricuspid regurgitation after the edge-to-edge
      technique in the specific experimental setup. Whether this reduction is
      sufficient to treat tricuspid regurgitation successfully in clinical practice
      remains to be established. Transcatheter approaches need to be evaluated further,
      probably with regard to concomitant annuloplasty for higher reduction of
      tricuspid regurgitation.

PMID- 29221744
TI  - It is all about the quality of the data.

PMID- 29221745
TI  - Upfront surgery as first-line therapy in selected patients with stage IIIA non
      small cell lung cancer.
AB  - OBJECTIVE: Surgery plays an important role in the multidisciplinary treatment
      strategy for patients with stage IIIA non-small cell lung cancer (NSCLC). Besides
      induction therapy, patients could benefit from surgery followed by adjuvant
      chemotherapy and radiotherapy. This study analyzed a subset of patients with
      pIIIA NSCLC who underwent upfront surgery as first-line therapy. METHODS:
      Selected patients with pIIIA NSCLC who received upfront surgery were
      retrospectively analyzed. Clinicopathologic characteristics and survival outcomes
      including progression-free survival (PFS) and overall survival (OS) were
      evaluated. RESULTS: A total of 668 patients were identified. Five hundred sixty
      five patients received adjuvant chemotherapy, and 157 patients received adjuvant
      radiotherapy after surgery. The median PFS and OS were 17.0 and 44.0 months,
      respectively. The 3-year and 5-year PFS rates were 31.6% and 21.0%, and the 3
      year and 5-year OS rates were 54.7% and 43.0%. Patients with adenocarcinoma (AD)
      had better OS than those with squamous cell carcinoma (5-year OS: P = .026).
      Patients with low-grade AD (acinar and papillar) had a similar PFS and OS
      compared with patients with high-grade AD (solid, micropapillary, and mucinous)
      (5-year PFS: P = .894; 5-year OS: P = .439). Patients with mutated epidermal
      growth factor receptor had a similar OS to patients with wild-type epidermal
      growth factor receptor (5-year OS: P = .121). Patients with clinical N0 status (P
      = .004) and patients with single-station of pathologic N2 (P < .001) had better
      OS. CONCLUSIONS: Upfront surgery followed by adjuvant therapy may provide
      favorable survival outcomes for selected patients with pIIIA NSCLC, especially
      for patients with AD or patients with clinical N0 and pathologic single-station
      N2 diseases.

PMID- 29221746
TI  - Clinical and neuroimaging characteristics of cerebral sinovenous thrombosis in
      neonates undergoing cardiac surgery.
AB  - OBJECTIVES: Neonates with congenital heart disease may have an increased risk of
      cerebral sinovenous thrombosis, but incidence rates are lacking. This study
      describes the clinical and neuroimaging characteristics of cerebral sinovenous
      thrombosis in neonates undergoing cardiac surgery. METHODS: Forty neonates (78%
      male) requiring neonatal univentricular or biventricular cardiac repair using
      cardiopulmonary bypass were included. All underwent preoperative (median
      postnatal day 7) and postoperative (median postoperative day 7) magnetic
      resonance imaging of the brain, including venography, to detect cerebral
      sinovenous thrombosis. Clinical characteristics were compared between cerebral
      sinovenous thrombosis positive and cerebral sinovenous thrombosis negative
      neonates. RESULTS: Postoperatively, cerebral sinovenous thrombosis was diagnosed
      in 11 neonates (28%), with the transverse sinus affected in all, and involvement
      of multiple sinuses in 10 (91%). Preoperatively, signs of thrombosis were seen in
      3 cases (8%). Focal infarction of the basal ganglia was significantly more common
      in cerebral sinovenous thrombosis positive than cerebral sinovenous thrombosis
      negative neonates (P = .025). Cerebral sinovenous thrombosis positive neonates
      spent more time in the intensive care unit preoperatively (P = .001), had lower
      weight (P = .024) and lower postmenstrual age (P = .030) at surgery, and had
      prolonged use of a central venous catheter (P = .023) and a catheter placed in
      the internal jugular vein more often (P = .039). Surgical and postoperative
      factors were not different between new postoperative cerebral sinovenous
      thrombosis positive and cerebral sinovenous thrombosis negative neonates.
      CONCLUSIONS: Cerebral sinovenous thrombosis might be more common than previously
      understood in neonates undergoing cardiac surgery. In our study, cerebral
      sinovenous thrombosis was associated with a higher risk of additional intra
      parenchymal brain injury.

PMID- 29221747
TI  - Value analysis committees: Not just another committee to get out of.

PMID- 29221748
TI  - Hydroxyethyl starch is associated with early postoperative delirium in patients
      undergoing esophagectomy.
AB  - OBJECTIVE: Postoperative delirium is associated with longer hospital stay and
      increased morbidities. Patients undergoing esophagectomy have a high chance of
      developing postoperative delirium because of their advanced age, comorbidities,
      and intensive care unit care. In this study, we investigated the risk factors of
      early postoperative delirium in patients undergoing esophagectomy, focusing on
      perioperative fluid type to test the hypothesis that colloids with high oncotic
      pressure and anti-inflammatory action would decrease the incidence of
      postoperative delirium compared with crystalloids. METHODS: All patients who
      underwent esophagectomy from 2010 to 2015 in a tertiary care center were reviewed
      in this retrospective study (n = 1041). Patients who showed positive Confusion
      Assessment Method or received haloperidol within 4 days postoperatively were
      enrolled as those with postoperative delirium (+). Multivariable logistic
      regression was performed to identify risk factors for postoperative delirium.
      Incidence of postoperative delirium was compared among crystalloids, hydroxyethyl
      starch, and albumin groups after propensity score matching. RESULTS: The
      incidence of delirium within postoperative 4 days was 22.7%. Infusion of
      hydroxyethyl starch was an independent risk factor (odds ratio [OR], 1.53; 95%
      confidence interval [CI], 1.09-2.14; P = .0151). Other risk factors were age (OR,
      1.04; 1.02-1.06, per year; P = .0002), preoperative cerebrovascular disease (OR,
      2.18; 1.15-4.12; P = .0170), pulmonary dysfunction (OR, 1.85; 1.33-2.58; P =
      .0003), and transfusion (OR, 1.76; 1.22-2.53; P = .0023). Propensity score
      matching analysis confirmed that administration of hydroxyethyl starch, but not
      albumin, is related to postoperative delirium. CONCLUSIONS: Old age, preoperative
      cerebrovascular disease, pulmonary dysfunction, transfusion, and hydroxyethyl
      starch administration were related to early postoperative delirium. If colloid
      must be administered, albumin is preferred to hydroxyethyl starch.

PMID- 29221749
TI  - Mitral surgery on the precipice of transformation.

PMID- 29221751
TI  - Bridging silos: Taking a page from the Alzheimer playbook.

PMID- 29221752
TI  - Chronic nicotine exposure impairs uncertainty modulation on reinforcement
      learning in anterior cingulate cortex and serotonin system.
AB  - Deficits in the computational processes of reinforcement learning have been
      suggested to underlie addiction. Additionally, environmental uncertainty, which
      is encoded in the anterior cingulate cortex (ACC), modulates reward prediction
      errors (RPEs) during reinforcement learning and exacerbates addiction. The
      present study tested whether and how the ACC would have an essential role in drug
      addiction by failing to use uncertainty to modulate the RPEs during reinforcement
      learning. In Experiment I, we found that the ACC/medial prefrontal cortex (MPFC)
      did not modulate RPE learning according to uncertainty in smokers. The effect of
      uncertainty * RPE in the ACC/MPFC was correlated with the learning rate of RPEs
      and the duration of nicotine use. Experiment II demonstrated that serotonin, but
      not dopamine, receptor mRNA expression significantly decreased in the ACC of the
      nicotine exposed compared to the control rats. Furthermore, there was a positive
      correlation between learning rate and serotonin receptor mRNA expression in the
      ACC. Therefore, all present results suggest that impairments in uncertainty
      modulation in the ACC disrupt reinforcement learning processes in chronic
      nicotine users and contribute to maladaptive decision-making. These findings
      support interventions for pathological decision-making in drug addiction that
      strongly focus on the serotonin system in ACC.

PMID- 29221750
TI  - Secondary surgical-site infection after coronary artery bypass grafting: A multi
      institutional prospective cohort study.
AB  - OBJECTIVE: To analyze patient risk factors and processes of care associated with
      secondary surgical-site infection (SSI) after coronary artery bypass grafting
      (CABG). METHODS: Data were collected prospectively between February and October
      2010 for consenting adult patients undergoing CABG with saphenous vein graft
      (SVG) conduits. Patients who developed a deep or superficial SSI of the leg or
      groin within 65 days of CABG were compared with those who did not develop a
      secondary SSI. RESULTS: Among 2174 patients identified, 65 (3.0%) developed a
      secondary SSI. Median time to diagnosis was 16 days (interquartile range 11-29)
      with the majority (86%) diagnosed after discharge. Gram-positive bacteria were
      most common. Readmission was more common in patients with a secondary SSI (34% vs
      17%, P < .01). After adjustment, an open SVG harvest approach was associated with
      an increased risk of secondary SSI (adjusted hazard ratio [HR], 2.12; 95%
      confidence interval [CI], 1.28-3.48). Increased body mass index (adjusted HR,
      1.08, 95% CI, 1.04-1.12) and packed red blood cell transfusions (adjusted HR,
      1.13; 95% CI, 1.05-1.22) were associated with a greater risk of secondary SSI.
      Antibiotic type, antibiotic duration, and postoperative hyperglycemia were not
      associated with risk of secondary SSI. CONCLUSIONS: Secondary SSI after CABG
      continues to be an important source of morbidity. This serious complication often
      occurs after discharge and is associated with open SVG harvesting, larger body
      mass, and blood transfusions. Patients with a secondary SSI have longer lengths
      of stay and are readmitted more frequently.

PMID- 29221754
TI  - Up-regulation of YPEL1 and YPEL5 and down-regulation of ITGA2 in erlotinib
      treated EGFR-mutant non-small cell lung cancer: A bioinformatic analysis.
AB  - PURPOSE: This study aimed to identify genes with significant alteration following
      treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung
      cancer (NSCLC) with tyrosine kinase inhibitors (TKIs). METHODS: We downloaded
      microarray data of GSE67051 from the Gene Expression Omnibus (GEO) database.
      Genes with differential expression were identified in two groups: erlotinib
      treated versus DMSO-treated PC9 cells and erlotinib-treated versus DMSO-treated
      HCC827 cells. Functional enrichment analysis and protein-protein interaction
      (PPI) network were performed on the overlapping differentially expressed genes
      (DEGs). Additionally, miRNAs that can regulate the DEGs were predicted. Small
      molecule drugs, with possible synergistic or antagonistic actions with respect to
      erlotinib, were screened; data validation using another dataset was conducted.
      RESULTS: In total, 1466 and 839 DEGs were identified in the aforementioned
      comparison groups, respectively, among which 267 overlapping up-regulated and 73
      down-regulated were observed. The overlapping up- and down-regulated genes were
      significantly associated with different functions and pathways. ITGA2 had higher
      centrality scores in the PPI network. Seventy small-molecule drugs, with either
      possible synergistic or antagonistic roles with erlotinib, were identified.
      Moreover, up-regulated YPEL1, YPEL2, and YPEL5 were enriched in the miRNA-target
      regulatory network. Implementing data validation, we found YPEL1, YPEL5, and
      ITGA2 displayed similar expression profiles in the two datasets. CONCLUSION:
      YPEL1 and YPEL5 may be related to the action of erlotinib, and down-regulation of
      ITGA2 may be associated with the development of acquired resistance to erlotinib
      in EGFR-mutant NSCLCs. Furthermore, several small-molecule drugs that may have
      synergistic and antagonistic roles with erlotinib were identified.

PMID- 29221755
TI  - Unilateral brachial plexopathy, a rare complication of Mycoplasma pneumoniae
      infection.
AB  - Few reports in the literature describe isolated peripheral neuropathies in
      relation to Mycoplasma pneumoniae infection without concurrent damage to the
      central nervous system. To our knowledge only a single case of mononeuritis
      multiplex with brachial plexus neuropathy coincident with M. pneumoniae has been
      documented until now. Here we present the first clinical case of lobar M.
      pneumoniae pneumonia in a 19-year-old female patient, where coincident
      neurological complications manifested as unilateral brachial plexus neuropathy,
      affecting axillar and suprascapular nerves. Isolated M. pneumoniae from sputum
      belonged to P1 type 2 and to MLVA type 3-6-6-2. No mutation associated with
      macrolide resistance in domain V of the 23S rRNA gene was detected. Serological
      testing of a GM1 antibody showed positive results, which might support the role
      of immunologic mechanisms in the pathogenesis of peripheral neuropathies related
      to M. pneumoniae infection.

PMID- 29221753
TI  - PURA, the gene encoding Pur-alpha, member of an ancient nucleic acid-binding
      protein family with mammalian neurological functions.
AB  - The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic
      acid binding domains that are highly conserved from bacteria through humans. PUR
      genes with a single copy of this domain have been detected so far in spirochetes
      and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas
      chordates possess 1 to 4 PUR family members. Human PUR genes encode Pur-alpha
      (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein
      that binds specific DNA and RNA sequence elements. Human PURA, located at
      chromosome band 5q31, is under complex control of three promoters. The entire
      protein coding sequence of PURA is contiguous within a single exon. Several
      studies have found that overexpression or microinjection of Pura inhibits
      anchorage-independent growth of oncogenically transformed cells and blocks
      proliferation at either G1-S or G2-M checkpoints. Effects on the cell cycle may
      be mediated by interaction of Pura with cellular proteins including Cyclin/Cdk
      complexes and the Rb tumor suppressor protein. PURA knockout mice die shortly
      after birth with effects on brain and hematopoietic development. In humans
      environmentally induced heterozygous deletions of PURA have been implicated in
      forms of myelodysplastic syndrome and progression to acute myelogenous leukemia.
      Pura plays a role in AIDS through association with the HIV-1 protein, Tat. In the
      brain Tat and Pura association in glial cells activates transcription and
      replication of JC polyomavirus, the agent causing the demyelination disease,
      progressive multifocal leukoencephalopathy. Tat and Pura also act to stimulate
      replication of the HIV-1 RNA genome. In neurons Pura accompanies mRNA transcripts
      to sites of translation in dendrites. Microdeletions in the PURA locus have been
      implicated in several neurological disorders. De novo PURA mutations have been
      related to a spectrum of phenotypes indicating a potential PURA syndrome. The
      nucleic acid, G-rich Pura binding element is amplified as expanded polynucleotide
      repeats in several brain diseases including fragile X syndrome and a familial
      form of amyotrophic lateral sclerosis/fronto-temporal dementia. Throughout
      evolution the Pura protein plays a critical role in survival, based on
      conservation of its nucleic acid binding properties. These Pura properties have
      been adapted in higher organisms to the as yet unfathomable development of the
      human brain.

PMID- 29221756
TI  - Characterization of the binding site for d-deprenyl in human inflamed synovial
      membrane.
AB  - AIMS: d-Deprenyl when used as a positron emission tomography tracer visualizes
      peripheral inflammation. The major aim of the current study was to identify and
      investigate the properties of the binding target for d-deprenyl in synovial
      membrane explants from arthritic patients. MAIN METHODS: Thirty patients
      diagnosed with arthritis or osteoarthritis were enrolled into the study.
      Homologous and competitive radioligand binding assays utilizing [3H]d-deprenyl
      were performed to investigate the biochemical characteristics of the binding site
      and assess differences in the binding profile in synovial membranes exhibiting
      varying levels of inflammation. KEY FINDINGS: The [3H]d-deprenyl binding assay
      confirmed the existence of a single, saturable population of membrane-bound
      protein binding sites in synovial membrane homogenates. The macroscopically
      determined level of inflammation correlated with an increase in [3H]d-deprenyl
      binding affinity, without significant alterations in binding site density.
      Selective monoamine oxidase B inhibitor, selegiline competed for the same site as
      [3H]d-deprenyl, but failed to differentiate the samples with regard to their
      inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed
      only weak displacement of [3H]d-deprenyl binding. No significant alterations in
      monoamine oxidase B expression was detected, thus it was not confirmed whether it
      could serve as a marker for ongoing inflammation. SIGNIFICANCE: Our study was the
      first to show the biochemical characteristics of the [3H]d-deprenyl binding site
      in inflamed human synovium. We confirmed that d-deprenyl could differentiate
      between patients with varying severity of synovitis in the knee joint by binding
      to a protein target distinct from monoamine oxidase B.

PMID- 29221757
TI  - An international, multicenter cohort study comparing 6 shoulder clinical scores
      in an asymptomatic population.
AB  - HYPOTHESIS: The study purpose was to assess 6 shoulder patient-reported outcome
      measure (PROM) values in asymptomatic, healthy, pathology-free individuals. We
      hypothesized that there would be no difference in PROM values in pathology-free
      individuals when considering sex, age, ethnicity, and geographical location.
      METHODS: Electronic questionnaires were completed by 635 individuals (323
      Australians and 312 Canadians) without dominant shoulder pathology for the
      American Shoulder and Elbow Surgeons (ASES) shoulder score; Constant-Murley
      Shoulder Score (CSS); Oxford Shoulder Score (OSS); University of California, Los
      Angeles (UCLA) shoulder score; Shoulder Pain and Disability Index (SPADI); and
      Stanmore Percentage of Normal Shoulder Assessment (SPONSA). Shoulder range of
      motion and strength were assessed. RESULTS: No difference was identified between
      subjective-only and subjective-objective PROMs. Handedness and a current elbow or
      wrist problem were not associated with differences in PROM values. Poorer PROM
      values were associated with a history of an inactive shoulder problem and
      increasing age. Female participants tended to report similar or poorer PROM
      scores. No significant difference was found between ethnicities. Geographical
      location was associated with differences in the ASES shoulder score, UCLA
      shoulder score, and SPADI but not the CSS, SPONSA, and OSS. CONCLUSIONS:
      Differences in sex, age, and geographical location will affect PROM shoulder
      scores in pathology-free individuals and should be taken into consideration when
      PROMs are being used to compare patient outcomes. This study has established
      normative values for the ASES shoulder score, CSS, OSS, UCLA shoulder score,
      SPADI, and SPONSA. Future studies assessing a pathologic patient cohort should
      perform comparisons against a sex- and age-matched control cohort, ideally
      sourced from the same geographical location.

PMID- 29221758
TI  - Oocyte vitrification for preserving fertility in patients with endometriosis:
      first observational cohort study... and many unresolved questions. Letter to the
      Editor.

PMID- 29221759
TI  - Clinically significant pedicle screw malposition is an underestimated cause of
      radiculopathy.

PMID- 29221760
TI  - Substrate specificity and transfucosylation activity of GH29 alpha-l-fucosidases
      for enzymatic production of human milk oligosaccharides.
AB  - Human milk oligosaccharides (HMOs) constitute a unique family of bioactive
      lactose-based molecules present in human breast milk. HMOs are of major
      importance for infant health and development but also virtually absent from
      bovine milk used for infant formula. Among the HMOs, the fucosylated species are
      the most abundant. Transfucosylation catalysed by retaining alpha-l-fucosidases
      is a new route for manufacturing biomimetic HMOs. Seven alpha-l-fucosidases from
      glycosyl hydrolase family 29 were expressed, characterized in terms of substrate
      specificity and thermal stability, and shown to be able to catalyse
      transfucosylation. The alpha-l-1,3/4-fucosidase CpAfc2 from Clostridium
      perfringens efficiently catalysed the formation of the more complex human milk
      oligosaccharide structure lacto-N-fucopentaose II (LNFP II) using 3
      fucosyllactose as fucosyl donor and lacto-N-tetraose as acceptor with a 39%
      yield. alpha-l-Fucosidases FgFCO1 from Fusarium graminearum and Mfuc5 from a soil
      metagenome were able to catalyse transfucosylation of lactose using citrus
      xyloglucan as fucosyl donor. FgFCO1 catalysed formation of 2'-fucosyllactose,
      whereas Mfuc5 catalysis mainly produced an unidentified, non-HMO fucosyllactose,
      reaching molar yields based on the donor substrate of 14% and 18%, respectively.

PMID- 29221761
TI  - Enrichment of PHA-producing bacteria under continuous substrate supply.
AB  - To enrich polyhydroxyalkanoate (PHA) producing microbial communities, generally,
      a feast-famine regime is applied. Here we investigated the impact of continuous
      substrate feeding on the enrichment of PHA-producing bacteria in two sequencing
      batch reactors (SBRs). In the first reactor, the substrate (acetate) was dosed
      continuously and Zoogloea sp. was enriched. The culture accumulated PHA upon
      exposure to excess carbon, but the PHA production rate and storage capacity (53
      wt.%) were one-fifth of that observed for enrichment cultures in a standard,
      pulse-fed SBR dominated by the PHA producer Plasticicumulans acidivorans. In the
      second reactor, half the acetate was dosed at the beginning of the cycle and the
      other half continuously. Having a true feast phase, the enrichment of P.
      acidivorans was not impeded by the continuous supply of acetate and the culture
      accumulated 85 wt.% PHA. This shows that for the enrichment of bacteria with a
      superior PHA-producing capacity periodic substrate excess - a true feast phase -
      is essential, while periodic substrate absence - a true famine phase - is not.

PMID- 29221762
TI  - Continuous Infusion of Cilengitide Plus Chemoradiotherapy for Patients With Stage
      III Non-Small-cell Lung Cancer: A Phase I Study.
AB  - INTRODUCTION: Because of our previous preclinical results, we conducted a phase I
      study associating the specific alphavbeta3/alphavbeta5 integrin inhibitor
      cilengitide, given as a continuous infusion, with exclusive chemoradiotherapy for
      patients with stage III non-small-cell lung cancer. PATIENTS AND METHODS: A
      standard 3+3 dose escalation design was used. Cilengitide was given as a
      continuous infusion (dose levels of 12, 18, 27, and 40 mg/h), starting 2 weeks
      before and continuing for the whole course of chemoradiotherapy (66 Gy combined
      with platinum/vinorelbine), and then at a dose of 2000 mg twice weekly in
      association with chemotherapy. 2-Deoxy-2-[fluorine-18]fluoro-d-glucose positron
      emission tomography (PET) and computed tomography scans were performed before and
      after the first 2 weeks of cilengitide administration and then every 3 months.
      RESULTS: Of the 14 patients included, 11 were evaluable for evaluation of the
      dose-limiting toxicities (DLTs). One DLT, a tracheobronchial fistula, was
      reported with the 40 mg/h dose. No relevant adverse events related to cilengitide
      were observed overall. At the PET evaluation 2 months after chemoradiotherapy, 4
      of 9 patients had a complete response and 4 had a partial response. The median
      progression-free and overall survival was 14.4 months (95% confidence interval
      [CI], 8.4 to not reached) and 29.4 months (95% CI, 11.73 to not reached),
      respectively. CONCLUSION: Cilengitide, given continuously with chemoradiotherapy,
      showed acceptable toxicity and gave encouraging clinical results.

PMID- 29221763
TI  - Cognitive impairment and quality of life of people with epilepsy and
      neurocysticercosis in Zambia.
AB  - Cognitive impairment and quality of life (Qol) are important to assess the burden
      of epilepsy and neurocysticercosis (NCC), which are common but neglected in Sub
      Saharan Africa (SSA). The aims of this study were to assess cognitive performance
      and Qol of people with epilepsy (PWE) in Zambia and to explore differences in PWE
      with and without NCC. In this community based, cross-sectional case-control
      study, 47 PWE and 50 healthy controls completed five neuropsychological tests
      (Mini Mental State Examination (MMSE), Digit Span, Selective Reminding Test
      (SRT), Spatial Recall Test (SPART), Test Battery of Attentional Performance
      (TAP)) and a World Health Organization (WHO) questionnaire of Qol. Comparisons
      were made between PWE (n=47) and healthy controls (n=50) and between PWE with NCC
      (n=28) and without NCC (n=19), respectively, using Analysis of Covariance
      (ANCOVA) and Linear Models (LMs) while correcting for confounders such as age,
      sex, and schooling years, and adjusting for multiplicity. Working memory, spatial
      memory, verbal memory, verbal learning, orientation, speech and language
      reception, visuoconstructive ability, and attentional performance were
      significantly reduced in PWE compared with healthy controls (ANCOVA and LM,
      p<0.05). Quality of life of PWE was significantly lower in three domains
      (psychological, social, environmental) and in overall Qol compared with healthy
      controls (ANCOVA, p<0.05). There were no significant differences between PWE with
      NCC and PWE without NCC detected by ANCOVA. Using LM, significant differences
      between the groups were detected in four tests, indicating worse performance of
      PWE without NCC in MMSE, Digit Span, SPART, and lower physical Qol. Epilepsy was
      found to be associated with cognitive impairment and reduced Qol. People with
      epilepsy due to NCC had similar cognitive impairment and Qol compared with PWE
      due to other causes. Further studies should investigate the role of different
      conditions of NCC and the role of seizures on cognition and Qol.

PMID- 29221764
TI  - Regulation of autophagy by polyphenols: Paving the road for treatment of
      neurodegeneration.
AB  - In the present paper, we will discuss on the importance of autophagy in the
      central nervous system, and outline the relation between autophagic pathways and
      the pathogenesis of neurodegenerative disorders. The potential therapeutic
      benefits of naturally occurring phytochemicals as pharmacological modulators of
      autophagy will also be addressed. Our findings provide renewed insight on the
      molecular modes of protection by polyphenols, which is likely to be at least in
      part mediated not only by their potent antioxidant and anti-inflammatory effects,
      but also through modulation of autophagic processes to remove the aberrant
      protein aggregates.

PMID- 29221765
TI  - Advances in fetal echocardiography.
AB  - The development of fetal echocardiography and success in prenatal cardiac
      screening programs over the past 30 years has been driven by technical innovation
      and influenced by the different approaches of the various specialties practicing
      it. Screening for congenital heart defects no longer focuses on examining a
      limited number of pregnant women thought to be at increased risk, but instead
      forms an integrated part of a high-quality anatomical ultrasound performed in the
      second trimester using the 'five-transverse view' protocol. A prenatal diagnosis
      is feasible in almost all cardiac lesions and the advantages to parents and to
      health professionals are well recognized. Prenatal evaluation can usually
      determine the level of care required at delivery, thereby reducing perinatal
      morbidity. However, only half of the babies undergoing surgery within the first
      year of life have a prenatal detection, and practical training programs to
      support and provide feedback to sonographers remain essential for continued
      improvement.

PMID- 29221766
TI  - Screening for fetal growth restriction and placental insufficiency.
AB  - Fetal growth restriction (FGR) continues to be a leading cause of preventable
      stillbirth and poor neurodevelopmental outcomes in offspring, and furthermore is
      strongly associated with the obstetrical complications of iatrogenic preterm
      birth and pre-eclampsia. The terms small for gestational age (SGA) and FGR have,
      for too long, been considered equivalent and therefore used interchangeably.
      However, the delivery of improved clinical outcomes requires that clinicians
      effectively distinguish fetuses that are pathologically growth-restricted from
      those that are constitutively small. A greater understanding of the
      multifactorial pathogenesis of both early- and late-onset FGR, especially the
      role of underlying placental pathologies, may offer insight into targeted
      treatment strategies that preserve placental function. The new maternal blood
      biomarker placenta growth factor offers much potential in this context. This
      review highlights new approaches to effective screening for FGR based on a
      comprehensive review of: etiology, diagnosis, antenatal surveillance and
      management. Recent advances in novel imaging methods provide the basis for
      stepwise multi-parametric testing that may deliver cost-effective screening
      within existing antenatal care systems.

PMID- 29221767
TI  - Editorial commentary: Interpreting and dealing with myocardial stunning.

PMID- 29221768
TI  - Current interpretation of myocardial stunning.
AB  - Myocardial stunning is a temporary post-ischemic cardiac mechanical dysfunction.
      As such, it is a heterogeneous entity and different conditions can promote its
      occurrence. Transient coronary occlusion, increased production of catecholamines
      and endothelin, and myocardial inflammation are all possible causes of myocardial
      stunning. Possible underlying mechanisms include an oxyradical hypothesis,
      calcium overload, decreased responsiveness of myofilaments to calcium, and
      excitation-contraction uncoupling due to sarcoplasmic reticulum dysfunction. The
      aim of this review is to summarize the clinical conditions that may be
      responsible for stunned myocardium.

PMID- 29221769
TI  - Actigraphy: a useful tool to monitor sleep-related hypermotor seizures.

PMID- 29221770
TI  - A simple intervention that markedly reduces the effectiveness of positive airway
      pressure.

PMID- 29221771
TI  - The sex-specific interaction between food responsiveness and sleep duration
      explaining body mass index among children.
AB  - OBJECTIVE/BACKGROUND: The inverse relationship between sleep duration and body
      mass index (BMI) has been well established and appears to be stronger among boys
      than girls. However, less is known about the mechanisms responsible for this sex
      specific link. The main aim of the current study was to examine the sex-specific
      interaction between food responsiveness and sleep duration in explaining BMI
      among children. This sex-specific moderation will give more insight into a
      possible underlying food intake mechanism. PATIENTS/METHODS: In total, 206
      caregivers filled out questionnaires on child's sleep duration and food
      responsiveness (49.5% boys; mean age = 9.5 years; standard deviation = 1.4
      years). Child's weight and height were measured, after which age- and sex
      specific standardized BMI values (referred to as zBMI here) were calculated.
      Descriptive statistics and regression analysis were conducted. A potential
      significant three-way interaction was further examined using simple slopes
      analysis and slope difference tests. RESULTS: A significant inverse correlation
      was found between sleep duration and zBMI for boys, but not for girls. Moreover,
      a significant and robust three-way interaction between sex, food responsiveness
      and sleep duration explaining child's zBMI was found. Slope difference tests
      indicate that the sleep-BMI slopes only significantly differed between high-food
      responsive boys and high-food-responsive girls and between high-food-responsive
      boys and low-food-responsive boys. CONCLUSIONS: These findings suggest that
      increased food intake might be a mechanism explaining the inverse sleep-BMI link
      among boys.

PMID- 29221772
TI  - Investigating psychological and physiological responses to the Trier Social
      Stress Test in young adults with insomnia.
AB  - OBJECTIVE: Stress and hyperarousal both contribute to insomnia. Elevated stress
      related sleep reactivity is associated with hyperarousal, and might constitute a
      vulnerability to future insomnia. The present study examined acute stress-induced
      arousal and its association with nocturnal sleep. METHODS: Participants were 30
      healthy adults (66.7% female, Mage = 26.7 years): 10 with insomnia (INS) and 20
      good sleepers with high vulnerability (HV) or low vulnerability (LV) to insomnia.
      They underwent two consecutive nights of polysomnography. During the evening
      preceding the second night, the Trier Social Stress Test (TSST) was administered,
      and psychological and physiological arousal indices were assessed. RESULTS: The
      TSST elicited an increase in psychological and physiological arousal in all three
      groups. The INS group showed greater acute cortisol response (p < 0.05) and
      secretion at bedtime (p < 0.05), and higher pre-sleep cognitive arousal (p <
      0.01) than the LV group; HV participants did not significantly differ from those
      in the INS or the LV group. Increased cortisol response and elevated
      sympathovagal imbalance (ie, low frequency/high frequency ratio) were each
      significantly associated with longer nocturnal awakenings (p = 0.048, p = 0.037,
      respectively). Heightened blood pressure was significantly associated with
      prolonged sleep onset latency, and reduced total sleep time and sleep efficiency
      (all ps < 0.05). CONCLUSIONS: These findings support the hyperarousal
      conceptualization of insomnia and indirectly suggest that increased stress
      reactivity and bedtime hyperarousal might represent a trait-like vulnerability in
      certain good sleepers. More research is warranted to validate and expand these
      preliminary findings.

PMID- 29221773
TI  - Gender differences in sleep symptoms after repeat concussions.
AB  - OBJECTIVES: There are notable gender differences in concussion as well as sleep.
      Sleep disturbance is a major symptom of post-concussive syndrome. The interplay
      between sleep disturbance, concussion, and gender has yet to be examined. The
      objective of this study was to determine whether sleep disturbance plays a role
      in the known gender differences associated with concussion. METHODS: Males and
      females (ages 10-35 years) completed a pre-concussion and post-concussion
      evaluation. Levels of sleep disturbance were assessed at baseline (N = 1284),
      after first concussion (N = 432) and after repeated concussions (one or more
      concussions, N = 296). Sleep disturbance levels were also compared among males
      and females with headaches, mood changes, and cognitive dysfunction. Analyses
      included group comparisons and correlations of post-concussive symptoms and
      cognitive dysfunction, respectively. Data was adjusted for age. RESULTS: Compared
      to males, females reported higher levels of sleep disturbance after a single
      concussion; however, levels of sleep disturbance equalized after repeated
      concussions. Females with higher levels of sleep disturbance had more headaches
      and more mood changes requiring medical treatment, compared to males. In
      addition, sleep disturbance was more strongly correlated with cognitive
      dysfunction in females compared to males. CONCLUSION: Gender differences in
      concussion recovery after repeat concussions may be primarily due to a difference
      in sleep disturbance between the genders. This difference in sleep appears to
      moderate the levels of other post-concussive symptoms. This indicates that sleep
      disturbance should be closely monitored and treated in females after a
      concussion. Further studies are required to determine the underlying reasons for
      these gender differences.

PMID- 29221774
TI  - Sleep-dependent motor sequence memory consolidation in individuals with periodic
      limb movements.
AB  - Periodic limb movements (PLMs) during sleep increase with age and are associated
      with striatal neurodegeneration and dopamine deficiency. Limb movements are often
      associated with disruptions to non-rapid eye movement (NREM) sleep. Motor skill
      memory consolidation recruits the striatum, and learning-dependent striatal
      activation is associated with NREM sleep. Therefore, we investigated whether de
      novo individuals who significantly experience elevated levels of PLMs but have
      not been formally diagnosed with periodic limb movement disorder had learning and
      sleep-related memory deficits and whether these deficits were related to sleep
      quality and symptom severity. In total, 14 adults with significantly elevated
      PLMs (PLM condition), 15 age-matched controls (CTRL), and 14 age-matched
      "disturbed" sleep (through induced leg movements) controls (CTRL-ES)
      participated. The participants were trained (PM) and retested (AM) on procedural
      motor sequence learning (MSL) and declarative paired associates memory tasks.
      Baseline sleep quality was significantly worse in PLM than in CTRL. Despite the
      continued presence of PLMs in the PLM condition on the experimental night,
      remarkably, sleep quality improved and arousals decreased, vs. baseline, and did
      not differ from CTRL. MSL was significantly slower in the PLM condition than in
      CTRL at training but surprisingly exhibited overnight performance gains, which
      correlated with reduced arousals. As predicted, CTRL but not CTRL-ES had
      overnight gains in MSL. Taken together, this suggests that in the PLM condition,
      sleep quality was normalized following MSL, where they derived the same benefit
      of sleep to procedural memory consolidation as in CTRL. Sleep did not benefit
      declarative memory. Although preliminary, these results suggest that MSL in
      individuals with PLMs may provide a benefit to sleep, which in turn may benefit
      memory consolidation.

PMID- 29221775
TI  - Short sleep and risk of proteinuria in 3-year-olds in Japan: a population-based
      cohort study.
AB  - OBJECTIVE: To examine whether short sleep at 18 months of age is associated with
      risk of proteinuria at 3 years of age. METHODS: A population-based cohort study
      using municipal health check-up data from 62,623 children born between March 1,
      2004, and April 30, 2011, and followed to 3 years via questionnaire in Kobe City,
      Japan. Sleep duration was calculated from wake time and bedtime at the 18-month
      health check-up by standardized parent-reported questionnaires. Proteinuria,
      defined as dipstick urinary protein of >=1+, was measured by dipstick urinalysis
      at 3 years. Multivariable logistic regression was used to generate adjusted olds
      ratios. RESULTS: In total, 2253 (3.6%) children had short nighttime sleep (<=8 h)
      at 18 months. At 3 years, 765 (1.2%) children had proteinuria. The adjusted odds
      ratio for proteinuria among children with 8 h of sleep or less versus those with
      normal sleep of 10 h per night was 1.50 (95% confidence interval, 1.07-2.11; P =
      0.02). Odds ratios of the same direction but weaker magnitude were observed for
      children with bedtime at 22:00 or later, and those with wake time at 6:00 or
      earlier. CONCLUSIONS: Short sleep at 18 months was associated with risk of
      proteinuria at 3 years. Future research is warranted to examine whether sleep
      programs targeting early childhood may have additional potential health benefits
      for kidney development.

PMID- 29221776
TI  - Sleep characteristics associated with drowsy driving.
AB  - OBJECTIVE: The aim of this study was to evaluate sleep characteristics associated
      with drowsy driving in an adult population. METHODS: The study subjects consisted
      of 1675 adults aged 19 years or older who completed a population-based
      questionnaire survey on sleep habits. Experiences of drowsy driving were obtained
      from self-reported data. We investigated sleep-related variables including sleep
      duration, sleep efficiency, chronotype, subjective sleep perception, daytime
      sleepiness, sleep quality, and snoring. We performed multivariate logistic
      regression analysis to determine sleep characteristics independently associated
      with drowsy driving. RESULTS: The mean age of the subjects was 43.2 years, and
      66.3% were men. The prevalence of self-reported drowsy driving was 23.6% (396 of
      1675), and 33.1% of subjects experienced dozing at the wheel at least once a
      month. Multivariate analysis demonstrated that men, office and manual workers,
      excessive daytime sleepiness, depression, habitual snoring, and perceived
      insufficient sleep were independently associated with drowsy driving. Subgroup
      analyses revealed that reduced weekday sleep duration was a risk factor of drowsy
      driving in adults with perceived sufficient sleep. On the other hand, frequent
      alcohol drinking significantly increased risk of drowsy driving in the subgroup
      with perceived sleep insufficiency. Furthermore, ordinal regression analyses
      confirmed the association between sleep characteristics and drowsy driving across
      different drowsy driving frequencies. CONCLUSION: Excessive daytime sleepiness,
      depression, habitual snoring, and perceived insufficient sleep were sleep-related
      risk factors for drowsy driving. In addition to maintaining healthy sleep habits,
      individuals at high risk should be encouraged to evaluate underlying sleep
      disorders or psychiatric problems to prevent drowsy driving.

PMID- 29221777
TI  - Prevalence of sleep apnea at the acute phase of ischemic stroke with or without
      thrombolysis.
AB  - OBJECTIVE: The aim of the study was to compare the prevalence, type, and severity
      of sleep apnea during the acute phase of ischemic stroke among patients either
      receiving or not receiving thrombolysis. METHODS: We recruited 246 consecutive
      adult ischemic stroke patients. Patients underwent cardiorespiratory sleep study
      with portable three-channel device during the first 48 h after the symptom onset
      of ischemic stroke. RESULTS: We enrolled 110 (65.5% male) stroke patients in the
      thrombolysis group and 94 (59.6% male) in the nonthrombolysis group. In the
      thrombolysis group, the median National Institutes of Health Stroke Scale (NIHSS)
      score was higher (5.5) compared to the nonthrombolysis group (2.0) (p < 0.001).
      There was a lower incidence of lacunar (17.3% vs 36.2%, p = 0.002) and cerebellar
      (2.7% vs 16.0%, p < 0.001) strokes and a higher frequency of middle cerebral
      artery syndrome (60.9% vs 33.0%, p < 0.001) in the thrombolysis group compared to
      the nonthrombolysis group. Sleep apnea defined as an apnea-hypopnea index (AHI)
      >= 5/h was diagnosed in 186 (91.2%) patients, its prevalence being higher in the
      thrombolysis (96.4%) compared to the nonthrombolysis (85.1%) group (p = 0.007).
      The mean baseline AHI was 33.7/h in the thrombolysis group compared to 26.8/h in
      the nonthrombolysis group (p = 0.017). CONCLUSION: Sleep apnea was present in the
      vast majority of ischemic stroke patients. The stroke patients treated with
      thrombolysis were more likely to have sleep apnea, to have elevated NIHSS score
      at admission, and to be younger. Sleep apnea was more severe among those
      receiving thrombolysis as compared to those who were not. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.cov. Unique identifier: NCT01861275.

PMID- 29221778
TI  - Long-term treatment with dopamine D3 receptor agonists induces a behavioral
      switch that can be rescued by blocking the dopamine D1 receptor.
AB  - Restless legs syndrome (RLS) is commonly treated with the dopamine agonists
      pramipexole, and rotigotine, which target the inhibitory dopamine receptor
      subtype D3R. While initially highly effective, these compounds lose their
      efficacy in treating RLS over time, and long-term therapy regularly leads to a
      worsening of the symptoms (augmentation). This dopamine agonist-induced
      augmentation has become a prime concern in the treatment of RLS, and while
      alternate therapies are being proposed, the mechanisms leading to augmentation
      remain opaque. Evidence suggests that the prolonged D3R treatment may lead to a
      hyper-dopaminergic state and involve the excitatory dopamine D1 receptor (D1R)
      subtype. We here present an animal model in which we can test acute and long-term
      effects of dopamine D3R agonists in a behavior setting relevant to RLS and in
      which we can induce a switch of the drug effect similar to the one observed in
      RLS patients under chronic therapy. We also present evidence that we can reverse
      this long-term effect by blocking the D1R. Together, data from our new animal
      model indicate that the mechanisms leading to augmentation in RLS patients after
      long-term use of the currently used dopamine receptor agonists may be related to
      a D3R-induced upregulation of the D1R system. As such, our model can be used to
      assess the interactions between D3R and D1R and unravel the mechanisms that lead
      to augmentation, and it has the potential to serve as a Launchpad for the
      development of new pharmacological strategies for the treatment of both RLS and
      augmentation.

PMID- 29221779
TI  - Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime
      sleep in narcolepsy.
AB  - OBJECTIVE: To assess the effects of three narcolepsy treatment modalities on
      sleep stage shifts associated with disrupted nighttime sleep (DNS) using data
      from a clinical trial. METHODS: Polysomnograms were reviewed from 155 patients
      (who had these data available at baseline and 8 weeks) of the 278 patients who
      were randomized to placebo, 9-g sodium oxybate (SXB)/nightly, 200-600 mg/d
      modafinil, or SXB + modafinil. Major outcomes of these post hoc analyses,
      analyzed using analysis of covariance, were change from baseline in number of
      shifts from Stages N2/3/rapid eye movement (REM) to Stage N1/Wake, and from Stage
      N1/Wake to REM. Sleep quality was evaluated using the sleep-quality question from
      the Pittsburgh Sleep Quality Index. RESULTS: SXB alone or in combination with
      modafinil significantly decreased the number of shifts from Stage N2/3/REM to
      Stage N1/Wake (p < 0.01); least-squares mean change in number of shifts from
      baseline was -0.6, -16.5, 1.8, and -13.7 in the placebo, SXB, modafinil and SXB +
      modafinil groups, respectively. A similar pattern was observed for changes in
      shifts from REM to Stage N1/Wake and from Stage N1/Wake to REM. Relative to
      placebo, sleep quality significantly improved with SXB and SXB + modafinil (p <=
      0.05) but not with modafinil alone. CONCLUSION: These results show that SXB with
      and without modafinil significantly consolidated sleep and improved patient
      reported sleep quality relative to placebo. In contrast, no such effects were
      observed with modafinil alone, suggesting a specific effect of SXB on DNS in
      addition to its effect on daytime sleepiness. CLINICALTRIALS. GOV IDENTIFIER:
      NCT00066170.

PMID- 29221780
TI  - Short sleep is associated with more depressive symptoms in a multi-ethnic cohort
      of older adults.
AB  - OBJECTIVES: To evaluate cross-sectional and prospective associations between
      short and long sleep duration and depressive symptoms in older adults (aged >65
      years). METHODS: The data from a subsample of the racially/ethnically diverse
      Northern Manhattan Study were analyzed. Depressive symptoms were assessed twice
      with the Center for Epidemiologic Studies Depression Scale (CES-D), approximately
      5 years apart. The presence of depressive symptoms was defined as a CES-D score
      >=16 or use of antidepressants. Self-reports of short (<6 h), intermediate (6-8
      h) and long (>=9 h) sleep were assessed prior to the initial CES-D. Logistic
      regression was used to evaluate the cross-sectional associations between short
      and long sleep durations with depressive symptoms, using intermediate sleep as
      the reference. The prospective association between sleep duration and depression
      in a sample of participants without depressive symptoms at first CES-D was also
      analyzed. All models were adjusted for demographic, behavioral, and vascular risk
      factors. RESULTS: The initial sample consisted of 1110 participants: 62% women,
      69% Hispanic, 17% black, 14% white. Short sleep was reported by 25%, intermediate
      sleep by 65%, and long sleep by 9%. Depressive symptoms were described in 25% of
      the initial sample. Short sleep, but not long sleep, was associated with
      depressive symptoms at baseline (adjusted OR 1.8, 95% CI 1.3-2.6), and at follow
      up (adjusted OR 1.9, 95% CI 1.1-3.5; median follow-up = 5.1 years). CONCLUSION:
      Short sleep duration had a cross-sectional and prospective association with
      depressive symptoms in an urban multi-ethnic cohort of older adults.

PMID- 29221781
TI  - Longitudinal associations between sleep and anxiety during pregnancy, and the
      moderating effect of resilience, using parallel process latent growth curve
      models.
AB  - BACKGROUND: For many women, pregnancy-related sleep disturbances and pregnancy
      related anxiety change as pregnancy progresses and both are associated with lower
      maternal quality of life and less favorable birth outcomes. Thus, the interplay
      between these two problems across pregnancy is of interest. In addition,
      psychological resilience may explain individual differences in this association,
      as it may promote coping with both sleep disturbances and anxiety, and thereby
      reduce their mutual effects. Therefore, the aim of the current study was to
      examine whether sleep quality and sleep duration, and changes in sleep are
      associated with the level of and changes in anxiety during pregnancy.
      Furthermore, the study tested the moderating effect of resilience on these
      associations. METHODS: At gestational weeks 14, 24, and 34, 532 pregnant women
      from the FinnBrain Birth Cohort Study in Finland filled out questionnaires on
      general sleep quality, sleep duration and pregnancy-related anxiety; resilience
      was assessed in week 14. RESULTS: Parallel process latent growth curve models
      showed that shorter initial sleep duration predicted a higher initial level of
      anxiety, and a higher initial anxiety level predicted a faster shortening of
      sleep duration. Changes in sleep duration and changes in anxiety over the course
      of pregnancy were not related. The predicted moderating effect of resilience was
      not found. CONCLUSIONS: The results suggested that pregnant women reporting
      anxiety problems should also be screened for sleeping problems, and vice versa,
      because women who experienced one of these pregnancy-related problems were also
      at risk of experiencing or developing the other problem.

PMID- 29221782
TI  - Sleep problems in children with autism spectrum disorder and intellectual
      disability without autism spectrum disorder.
AB  - OBJECTIVE: The objective of this study was to evaluate the sleep problems and
      their correlations in children with autism spectrum disorder (ASD), intellectual
      disability without ASD (ID), and typically developing children (TDC). METHODS:
      This study included 142 children (48 with ASD, 46 with ID, 48 with TDC) aged
      between 2 and 18 years old. Parents of the children completed the Childhood Sleep
      Habits Questionnaire (CSHQ) in order to evaluate sleep disturbances. The
      sociodemographic and clinical information were noted on a data form for each
      child. RESULTS: The mean total score of CSHQ was 41.56, 47.89 and 51.78
      respectively in TDC, ASD and ID groups. While the total CSHQ score was
      significantly lower in TDC, there was no significant difference between ID and
      ASD groups (p = 0.09). It was revealed that children having a neurodevelopmental
      disorder had a 2.8-fold increased risk of sleep disturbance, history of sleep
      disorder in the parents had a 3.1-fold increased risk, psychiatric comorbidity in
      the child had a 3.3-fold increased risk, and co-sleeping with parents had 13.1
      fold increased risk. However, in the binary regression analysis, co-sleeping with
      parents and family history of sleep problems significantly increased the risk of
      sleep disturbance. CONCLUSION: Sleep disturbances are more frequent in children
      with ASD and ID than TDC. Co-sleeping with parents and family history of sleep
      problems increase the risk of sleep disturbances. Thus, behavioral techniques
      especially focusing on co-sleeping problems and focusing on parents' sleep habits
      may improve the sleep disturbances in children with ID and ASD.

PMID- 29221783
TI  - The effect of sleep duration and sleep quality on hypertension in middle-aged and
      older Chinese: the Dongfeng-Tongji Cohort Study.
AB  - OBJECTIVE: To examine the independent and combined associations of sleep duration
      and sleep quality with hypertension in a middle-aged and older Chinese
      population. METHODS: We included 21,912 individuals aged 62.2 years at baseline
      from September 2008 to June 2010, and they were followed until October 2013.
      Sleep duration was self-reported and sleep quality was evaluated with questions
      designed according to the Pittsburgh Sleep Quality Index. Hypertension was
      defined as blood pressure >=140/90 mmHg, or self-reported physician diagnosis of
      hypertension, or self-reported current use of antihypertensive medication.
      RESULTS: In the cross-sectional analyses, the odds ratio of hypertension
      prevalence was significantly elevated (OR = 1.13, 95% CI = 1.03-1.24) in those
      who slept less than 7 h after adjusting for sex, age, body mass index, midday
      napping, cigarette smoking and sleep quality. It was particularly evident among
      males (OR = 1.19, 95% CI = 1.01-1.40) and individuals who were thin (OR = 2.00,
      95% CI = 1.01-3.93) with full adjustment. The association was also found for
      sleep duration of 9~<10 h after adjusting various covariates (OR = 1.14, 95% CI =
      1.04-1.27). In addition, impaired sleep quality was only associated with
      hypertension in obese individuals (OR = 1.25, 95% CI = 1.02-1.50), not in other
      subgroups. However, no significant association was detected in any category of
      sleep duration or sleep quality in all models in the prospective analyses, and
      the results remained unchanged in the subgroup analyses of sex, age and body mass
      index. CONCLUSIONS: The results of this study provide limited support for
      association of sleep duration and sleep quality with hypertension in middle-aged
      and older Chinese. Further studies are needed to confirm the results.

PMID- 29221784
TI  - Assessment of intervention-related changes in non-rapid-eye-movement sleep depth:
      importance of sleep depth changes within stage 2.
AB  - OBJECTIVES: Depth of sleep within non-rapid-eye-movement (non-REM) stage-2 (N2
      depth) varies from being nearly similar to stage-1 to nearly similar to stage-3.
      Differences in N2-depth are not captured by conventional indices of sleep depth
      (N1-N3 times, arousal/awakening index) when comparing sleep depth under different
      conditions. Magnitude of changes in N2-depth in the same individual under
      different experimental conditions, and the importance of measuring these changes
      are unknown. METHODS: We measured sleep depth using the odds-ratio-product (ORP),
      a continuous index of sleep depth (0 = deep sleep, 2.5 = full wakefulness)
      (Younes et al. (2015) ORP of sleep EEG as a continuous measure of sleep state.
      Sleep 38(4):641-54.). ORP in stage 2 (ORPN2) and in all non-REM (ORPNR) were
      measured, along with conventional indices (1) in the first and second halves of
      the night in 34 patients with no pathology, and (2) before and on continuous
      positive airway pressure (CPAP) in 75 patients with obstructive apnea. RESULTS:
      In most (31/34) 'no pathology' patients, ORPN2 and ORPNR were unchanged (DeltaORP
      -0.05 to 0.05; N = 15) or higher (0.1-0.63) in the second half. Changes in ORPN2
      on CPAP were bidirectional and often large (5-95% confidence interval was -0.62
      to 0.25). There was an excellent correlation between DeltaOPRN2 and DeltaORPNR in
      both groups (r > 0.90) emphasizing the importance of changes in N2-depth, when
      they occur, to changes in overall sleep depth. Changes in N1 time, N3 time and
      arousal/awakening index also correlated, but less strongly, with DeltaORPNR (r =
      0.76, -0.54, 0.69, respectively). CONCLUSIONS: N2 sleep depth can change
      dramatically in the same individual under different conditions. Ignoring these
      changes may result in inaccurate assessment of changes in overall non-REM sleep
      quality.

PMID- 29221785
TI  - Attention deficit hyperactivity disorder symptom severity and sleep problems in
      adult participants of the Netherlands sleep registry.
AB  - BACKGROUND: We examined whether current overall attention deficit hyperactivity
      disorder (ADHD), inattention, or hyperactivity symptom severities are associated
      with the current presence and persistent history of sleep problems. METHODS: N =
      942 participants of the Netherlands Sleep Registry filled out online several
      validated questionnaires. Regression analyses were performed to assess the
      association between (1) current overall ADHD symptom severity and the current
      presence of sleep problems, (2) current ADHD symptom-severity groups and the
      persistent history of sleep problems, and (3) current inattention or
      hyperactivity symptom severities and the current presence of sleep problems.
      RESULTS: (1) Current overall ADHD symptom severity was associated with the odds
      of suffering from probable obstructive sleep apnea syndrome (OSAS), restless legs
      syndrome (RLS), periodic limb movement disorder (PLMD), insomnia disorder (ID)
      with predominant difficulties initiating sleep (DIS) and maintaining sleep (DMS),
      but not with the odds of suffering from narcolepsy or ID with predominant early
      morning awakening (EMA). Current overall ADHD symptom severity was also
      associated with an extreme evening chronotype but not with short sleep. (2) The
      group with the most severe current ADHD symptoms was more likely to have a
      history of persistent OSAS, RLS, and ID. (3) The severity of symptoms of
      hyperactivity, but not of inattention, was specifically associated with probable
      RLS, PLMD, ID with DIS or DMS, and short sleep. Inattention symptom severity was
      only related to the probability of being an extreme evening chronotype.
      CONCLUSION: ADHD severity, especially the severity of hyperactivity, is
      associated with the current presence and persistent history of sleep problems.

PMID- 29221786
TI  - Access to excluded structures after Roux-en-Y gastric bypass: Experience in a
      high-level bariatric center without a technical platform for endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND: Rapid weight loss after bariatric surgery is associated with a high
      prevalence of gallstone formation. In laparoscopic Roux-en-Y gastric bypass
      (RYGBP), the bypassed segment is not readily available for endoscopic or
      radiographic examination. We propose a laparoscopic Janeway gastrostomy for
      secondary access to excluded structures in bariatric centers with no mandatory
      technical equipment in endoscopic retrograde cholangiopancreatography (ERCP),
      double-balloon ERCP or spiral enteroscopy. METHOD: This was a single-institution
      retrospective review of a prospectively collected database of patients with a
      history of laparoscopic RYGBP who underwent laparoscopic Janeway gastrostomy for
      duodenal and biliary access. The operative indications, technical aspects,
      endoscopic findings, outcomes, and complications were investigated. RESULTS: Five
      patients with a history of RYGBP underwent laparoscopic Janeway gastrostomy for
      exploration of the bypassed segment. All of them had biliary pathology, and all
      underwent successful ERCP and papillotomy. The gastrostomies were closed
      secondarily. The mean duration of hospitalization was 12 days. No complications
      developed. All procedures were performed laparoscopically. CONCLUSION: If access
      to excluded structures and simultaneous ERCP was not possible, temporary
      laparoscopic Janeway gastrostomy could be the last option alternative for a
      staged ERCP to gain access to the bypassed structures. It is a feasible and safe
      solution for the exploration and treatment of patients with a history of RYGBP in
      bariatric centers that have no endoscopists with expertise in ERCP.

PMID- 29221787
TI  - Evaluation of alternative serum biomarkers to monitor the progression of chronic
      HBV and HCV infection.
AB  - Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among
      the most serious health conditions affecting about 600 million people worldwide
      leading to a number of severe liver diseases. Due to the lack of warning signs or
      mild symptoms during the early stage of the infection, a molecular signature
      associated with disease progression would be useful. Based on our recent paper
      where candidate biomarkers were determined through topological and modularity
      analysis of protein interaction networks (PINs), this study was focused on the
      evaluation of MIF, TNFRSF1A, FAS and TMSB4X as diagnostic biomarkers in chronic
      HBV and HCV infections. The aim was to establish a molecular profile, by
      combining those markers, that would discriminate the different stages during the
      progression of chronic hepatitis. One hundred and fifteen patients infected with
      HBV or HCV categorized into three groups: non-cirrhotic, cirrhotic and with HCC,
      and 20 healthy subjects were enrolled in this study. Serum levels of the
      aforementioned factors were measured by ELISA. TNFRSF1A serum levels appeared
      statistically significantly increased in all patient groups compared to control
      group with a p-value of <0.05. Furthermore, the combination of TNFRSF1A and
      TMSB4X serum levels successfully classified 63, 47% of patients indicating an
      association with HBV and HCV infections. Thus, variations of serum levels of
      TNFRSF1A and TMSB4X could be associated with the different stages of the disease
      and may be utilized for further research. On the other hand, we found no
      contribution of MIF and FAS serum levels for successful classification of
      patients.

PMID- 29221788
TI  - Differential prevalence of hematuria and proteinuria with socio-demographic
      factors among school children in Hualien, Taiwan.
AB  - BACKGROUND: Pediatric hematuria/proteinuria is a risk factor for chronic kidney
      disease in later life, and school urinary screening can detect asymptomatic
      glomerulonephritis in the early stage. This study aimed to evaluate the
      prevalence of hematuria/proteinuria and its association with different socio
      demographic factors among school children in 2013 in Hualien, Taiwan. METHODS: A
      cross-sectional study was conducted among first, fourth, and seventh graders.
      Health examination results and urinalysis data were analyzed. Logistic regression
      models were used to the simultaneously analyze the association between the
      prevalence of hematuria/proteinuria and socio-demographic factors. RESULTS: A
      total of 9544 students were included. The overall prevalence of hematuria and
      proteinuria was 4.1% and 5.7%, respectively. Students who were females, of a high
      grade level, of aboriginal ethnicity, and living in rural areas had higher
      hematuria risk (all P < 0.001) than other students. Underweight students had low
      odds ratio (0.53) of hematuria (P < 0.001). Seventh-grade students had higher
      odds ratio (3.63) of proteinuria than first grade students (P < 0.001). Students
      with both parents of aboriginal descent had lower odds ratio (0.81) of
      proteinuria than those with non-aboriginal parents (P = 0.044). Only higher grade
      level students had significantly higher risk of combined hematuria and light
      proteinuria (odds ratio: 10.67) and heavy proteinuria with/without hematuria
      (odds ratio: 3.22) than first graders. CONCLUSION: Increased
      hematuria/proteinuria prevalence was noted in our county as compared to prior
      studies. Hematuria/proteinuria was significantly associated with gender, grade
      level, body mass index, ethnicity, and residence urbanization. Our data can be
      used for future longitudinal dataset collection to prevent pediatric renal
      disorders in Taiwan.

PMID- 29221789
TI  - Pretherapy neutrophil to lymphocyte ratio and platelet to lymphocyte ratio do not
      predict survival in resectable pancreatic cancer.
AB  - BACKGROUND: Pretherapy serum neutrophil to lymphocyte ratio (NLR) and platelet to
      lymphocyte ratio (PLR) have both been identified as prognostic in pancreatic
      ductal adenocarcinoma (PDAC). The aim of this study was to identify the
      prognostic implication of pretherapy NLR and PLR in patients with resectable
      PDAC. METHODS: Data were collected retrospectively on patients operated at our
      institution between 2004 and 2014. A Cox proportional hazards model was used to
      investigate the relationship between clinical and pathological parameters, NLR
      and PLR to overall survival (OS). Survival data were analyzed using the Kaplan
      Meier method. RESULTS: 217 patients were analyzed with a median overall survival
      (OS) of 17.5 months. Factors identified as being predictive of OS by univariate
      analysis included age, receipt of adjuvant therapy, margin positivity, pathologic
      angiolymphatic invasion, T-stage, and N-stage (P < 0.05). Factors identified as
      being independently predictive of OS by multivariate analysis included age and
      angiolymphatic invasion (P < 0.05). NLR and PLR were not predictive of OS.
      Survival analysis demonstrated no difference in OS in patients who had high or
      low NLR or PLR. DISCUSSION: Pretherapy NLR and PLR do not predict survival in
      patients who underwent pancreatectomy for PDAC at our institution.

PMID- 29221790
TI  - FAM3 gene family: A promising therapeutical target for NAFLD and type 2 diabetes.
AB  - Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health
      issues worldwide. The Family with sequence similarity 3 (FAM3) gene family
      consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D,
      respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and
      FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression
      is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A
      restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate
      steatosis and hyperglycemia in obese diabetic mice. FAM3C expression is also
      reduced in the liver under diabetic condition. FAM3C is a new hepatokine that
      activates HSF1-CaM-Akt pathway and represses mTOR-SREBP1-FAS pathway to suppress
      hepatic gluconeogenesis and lipogenesis. In contrast, hepatic expression of
      FAM3B, also called PANDER, is increased under obese state. FAM3B promotes hepatic
      lipogenesis and gluconeogenesis by repressing Akt and AMPK activities, and
      activating lipogenic pathway. Under obese state, the imbalance among hepatic
      FAM3A, FAM3B and FAM3C signaling networks plays important roles in the
      pathogenesis of NAFLD and type 2 diabetes. This review briefly discussed the
      latest research progress on the roles and mechanisms of FAM3A, FAM3B and FAM3C in
      the regulation of hepatic glucose and lipid metabolism.

PMID- 29221792
TI  - The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely
      moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors.
AB  - 5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT1A/5-HT2A receptor
      agonist. Its ability to evoke hallucinations could be used to study the
      neurobiology of psychotic symptoms and to identify new treatment targets.
      Moreover, recent studies revealed the therapeutic potential of serotonin
      hallucinogens in treating mood and anxiety disorders. Our previous results in
      anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT1A and
      5-HT2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in
      prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of
      freely-moving wild-type (WT) and 5-HT2A-R knockout (KO2A) mice. We performed
      local field potential multi-recordings evaluating the power at different
      frequency bands and coherence between areas. We also examined the prevention of 5
      MeO-DMT effects by the 5-HT1A-R antagonist WAY-100635. 5-MeO-DMT affected
      oscillatory activity more in cortical than in thalamic areas. More marked effects
      were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band
      coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5
      MeO-DMT effects on oscillatory activity. The present results indicate that
      hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration
      of prefrontal and visual activities. The prevention of these effects by WAY
      100635 in KO2A mice supports the potential usefulness of 5-HT1A receptor
      antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta
      activity and cortico-thalamic coherence may be related to its antidepressant
      activity. This article is part of the Special Issue entitled 'Psychedelics: New
      Doors, Altered Perceptions'.

PMID- 29221791
TI  - Online effects of transcranial direct current stimulation on prefrontal
      metabolites in gambling disorder.
AB  - Gambling disorder is characterized by persistent maladaptive gambling behaviors
      and is now considered among substance-related and addictive disorders. There is
      still unmet therapeutic need for these clinical populations, however recent
      advances indicate that interventions targeting the Glutamatergic/GABAergic system
      hold promise in reducing symptoms in substance-related and addictive disorders,
      including gambling disorder. There is some data indicating that transcranial
      direct current stimulation may hold clinical benefits in substance use disorders
      and modulate levels of brain metabolites including glutamate and GABA. The goal
      of the present work was to test whether this non-invasive neurostimulation method
      modulates key metabolites in gambling disorder. We conducted a sham-controlled,
      crossover, randomized study, blinded at two levels in order to characterize the
      effects of transcranial direct current stimulation over the dorsolateral
      prefrontal cortex on neural metabolites levels in sixteen patients with gambling
      disorder. Metabolite levels were measured with magnetic resonance spectroscopy
      from the right dorsolateral prefrontal cortex and the right striatum during
      active and sham stimulation. Active as compared to sham stimulation elevated
      prefrontal GABA levels. There were no significant changes between stimulation
      conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in
      striatal metabolite levels. Results also indicated positive correlations between
      metabolite levels during active, but not sham, stimulation and levels of risk
      taking, impulsivity and craving. Our findings suggest that transcranial direct
      current stimulation can modulate GABA levels in patients with gambling disorder
      which may represent an interesting future therapeutic avenue.

PMID- 29221793
TI  - Pannexin-1 channel dysfunction in the medial prefrontal cortex mediates
      depressive-like behaviors induced by chronic social defeat stress and
      administration of mefloquine in mice.
AB  - Mefloquine (MFQ) is widely used for the treatment of malaria clinically. Apart
      from antimalarial effect, psychiatric side effects such as depression and anxiety
      of MFQ have been reported. Interestingly, MFQ is also known as a broad-spectrum
      pannexin-1 (Panx1) inhibitor. Panx1 is a new gap junction channel in the brain
      which mediates efflux of adenosine triphosphate (ATP). Although exogenous ATP has
      been known to produce a potential antidepressant-like effect, little is known
      about the role of Panx1 in pathophysiology of depression, especially the
      depression induced by administration of MFQ. Here, we used the chronic social
      defeat stress (CSDS) model and found a decrease in the expression and function of
      Panx1 in the medial prefrontal cortex (mPFC) of susceptible mice. Furthermore,
      pharmacological blockade of Panx1 in the mPFC with carbenoxolone (CBX) (100 mM)
      or 10Panx (100 MUM) was sufficient to induce depressive-like behaviors and
      increase vulnerability to stress in mice, which were prevented by preconditioning
      with ATP (25 MUM). Finally, systemic and intral-mPFC injection of MFQ both
      inhibited the activity of Panx1 and induced depressive-like and anxiety behaviors
      in mice with sub-threshold social defeat stress. Indeed, the behavioral
      abnormalities induced by MFQ were prevented by preconditioning with ATP in the
      mPFC. In conclusion, our study demonstrates a role of the Panx1 channel in
      chronic stress and MFQ-induced depressive-like and anxiety behaviors, which may
      provide a novel molecular mechanism for psychiatric side effects of MFQ.

PMID- 29221795
TI  - Comparison of Local Anesthetic Efficiency of Tramadol Hydrochloride and Lidocaine
      Hydrochloride.
AB  - PURPOSE: This study investigated the local anesthetic efficiency of tramadol
      versus lidocaine hydrochloride in maxillary infiltration anesthesia. MATERIALS
      AND METHODS: This study was a randomized double-blinded study involving 50
      healthy volunteers. In the experimental part of this study, each volunteer
      received a buccal 0.5-mL injection of tramadol hydrochloride 25 mg on one side
      and a buccal 0.5-mL injection of vasoconstrictor-free lidocaine hydrochloride 20
      mg on the other side. No other treatment was performed. After the injections,
      total duration of anesthesia, start and finish times of anesthesia, soft tissue
      (sensory) innervation, depth of anesthetic, possible side effects, and
      satisfaction levels were recorded from all volunteers. RESULTS: There was no
      relevant difference between solutions for total anesthesia duration and peak
      values. However, statistically, the effect of lidocaine started and ended early.
      The efficacy of tramadol was markedly more effective in the gingiva and skin,
      especially at 15 and 20 minutes, compared with lidocaine. Both anesthetic agents
      were well tolerated by the volunteers. CONCLUSION: Tramadol hydrochloride can be
      a good alternative to local anesthetic agents and beneficial to support
      anesthesia during long operations.

PMID- 29221794
TI  - GLP-1 action in the mouse bed nucleus of the stria terminalis.
AB  - Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake.
      Similarly, activation of preproglucagon (PPG) cells in the hindbrain which
      synthesize GLP-1, reduces food intake. However, it is far from clear whether this
      happens because of satiety, nausea, reduced reward, or even stress. Here we
      explore the role of the bed nucleus of the stria terminalis (BNST), an area
      involved in feeding control as well as stress responses, in GLP-1 responses.
      Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R
      expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression. The BNST
      displayed many varicose YFP+ PPG axons in the ventral and less in the dorsal
      regions. Mice which express RFP in GLP-1R neurons had RFP+ cells throughout the
      BNST with the highest density in the dorsal part, suggesting that PPG neuron
      derived GLP-1 acts in the BNST. Indeed, injection of GLP-1 into the BNST reduced
      chow intake during the dark phase, whereas injection of the GLP-1 receptor
      antagonist Ex9 increased feeding. BNST-specific GLP-1-induced food suppression
      was less effective in mice on high fat (HF, 60%) diet, and Ex9 had no effect.
      Restraint stress-induced hypophagia was attenuated by BNST Ex9 treatment, further
      supporting a role for endogenous brain GLP-1. Finally, whole-cell patch clamp
      recordings of RFP+ BNST neurons demonstrated that GLP-1 elicited either a
      depolarizing or hyperpolarizing reversible response that was of opposite polarity
      to that under dopamine. Our data support a physiological role for BNST GLP-1R in
      feeding, and suggest complex cellular responses to GLP-1 in this nucleus.

PMID- 29221796
TI  - Synthesis and antibacterial activity of new peptides from Alfalfa RuBisCO protein
      hydrolysates and mode of action via a membrane damage mechanism against Listeria
      innocua.
AB  - In this work we evaluated the mode of action of six new synthesized peptides (Met
      Asp-Asn; Glu-leu-Ala-Ala-Ala-Cys; Leu-Arg-Asp-Asp-Phe; Gly-Asn-Ala-Pro-Gly-Ala
      Val-Ala; Ala-Leu-Arg-Met-Ser-Gly and Arg-Asp-Arg-Phe-Leu), previously identified,
      from the most active peptide fractions of RuBisCO peptic hydrolysate against
      Listeria innocua via a membrane damage mechanism. Antibacterial effect and the
      minimum inhibitory concentrations (MIC) of these peptides were evaluated against
      six strains and their hemolytic activities towards bovine erythrocytes were
      determined. Prediction of the secondary structure of peptides indicated that
      these new antibacterial peptides are characterized by a short peptide chains (3-8
      amino acid) and a random coli structure. Moreover, it was observed that one key
      characteristic of antibacterial peptides is the presence of specific amino acids
      such as cysteine, glycine, arginine and aspartic acid. In addition the
      determination of the extracellular potassium concentration revealed that
      treatment with pure RuBisCO peptides could cause morphological changes of L.
      innocua and destruction of the cell integrity via irreversible membrane damage.
      The results could provide information for investigating the antibacterial model
      of antibacterial peptides derived from RuBisCO protein hydrolysates.

PMID- 29221797
TI  - Evaluation of dose dependent antimicrobial activity of self-assembled chitosan,
      nano silver and chitosan-nano silver composite against several pathogens.
AB  - The aim of this investigation to preparation of silver nanoparticles organized
      chitosan nano polymer, which effective against microbial and pathogens, when
      apply to liquid medium and edible food products surface, will rescue the growth
      of microbes. Self-assembly approach used to synthesis of silver nanoparticles and
      silver nanoparticles organized chitosan nano polymer. Silver nanoparticles and
      silver nanoparticles organized chitosan nano polymer and film characterized using
      Ultra-violate visible spectrometer (UV-vis), X-ray diffraction (X-ray), and
      Scanning electronic microscope (SEM). The crystalline structured protein capped
      nano silver successfully synthesized at range of 12 nm-29 nm and organized into
      chitosan nano polymer. Antimicrobial ingredient in liquid medium and food product
      surface provide to rescue oxidative change and growth of microorganism to provide
      higher safety. The silver nanoparticles organized chitosan nano polymer caused
      the death of microorganism. The materials in nano scale synthesized successfully
      using self-assembly method, which showed good antimicrobial properties.

PMID- 29221799
TI  - Editorial Comment.

PMID- 29221798
TI  - Association of heterozygous CCR5Delta32 deletion with survival in HIV-infection:
      A cohort study.
AB  - The role of a 32 base pair deletion in the CCR5 gene (CCR5Delta32) in HIV-disease
      progression and response to combined antiretroviral therapy (cART) is well
      established. However, the impact of CCR5Delta32 in the long-term survival pre
      cART and after cART introduction in a large cohort of HIV-infected patients is
      unknown. We analyzed the association of CCR5Delta32 deletion in the long-term
      survival of HIV-infected patients recruited between June 1981 and October 2016 (n
      = 1006). Clinical and epidemiological variables were recorded and CCR5Delta32
      deletion was assessed by PCR and electrophoretic analysis. The association of
      CCR5Delta32 deletion with the time to death was analyzed by Log-Rank tests and
      Cox Regression models. The CCR5 WT/Delta32 prevalence was 13.4% (n = 135). We did
      not find any homozygous subject for CCR5Delta32 deletion. AIDS (n = 85, 41.5%)
      and non-AIDS (n = 87, 42.4%) events were the main causes of 205 deaths.
      CCR5Delta32 deletion was independently associated with survival (p = 0.022;
      hazard ratio (HR): 0.572, confidence interval (CI) [0.354-0.923]), after
      adjusting by HIV diagnosis before 1997, age at diagnosis, being on cART, risk of
      transmission, nadir CD4+ T-cell counts and CDC stage C. This result was
      reproduced when the analysis was restricted to patients on cART (p = 0.045; HR:
      0.530 [0.286-0.985]). These results confirm the protective role of CCR5Delta32,
      and extend it to the long-term survival in a large cohort of HIV-infected
      patients. Beyond its antiviral effect, CCR5Delta32 enhanced the long-term
      survival of patients on cART.

PMID- 29221800
TI  - Gut Microbiome and Antibiotics.
AB  - Despite that the human gastrointestinal tract is the most populated ecological
      niche by bacteria in the human body, much is still unknown about its
      characteristics. This site is highly susceptible to the effects of many external
      factors that may affect in the quality and the quantity of the microbiome.
      Specific factors such as diet, personal hygiene, pharmacological drugs and the
      use of antibiotics can produce a significant impact on the gut microbiota. The
      effect of these factors is more relevant early in life, when the gut microbiota
      has not yet fully established. In this review, we discussed the effect of type
      and doses of the antibiotics on the gut microbiota and what the major
      consequences in the use and abuse of these antimicrobial agents.

PMID- 29221801
TI  - Donor Polymorphisms of Toll-like Receptor 4 rs1927914 Associated with the Risk of
      Hepatocellular Carcinoma Recurrence Following Liver Transplantation.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after liver transplantation
      (LT) severely restricts the long-term survival of patients. Toll-like receptor 4
      (TLR4) has been considered to be involved in hepatocarcinogenesis and metastasis.
      Additionally, there is a study demonstrating the significant association between
      TLR4 gene rs1927914 polymorphism and HCC, but no study investigated the
      association of the TLR4 rs1927914 polymorphism with the risk of HCC recurrence
      following LT. AIM: The purpose of this study was to assess the potential
      association between the TLR4 gene rs1927914 polymorphism of donors and recipients
      and hepatocellular carcinoma recurrence after LT. METHODS: Eighty-three patients
      with HCC undergoing LT from July 2006-June 2015 were identified for this
      analysis. We genotyped a single-nucleotide polymorphism (rs1927914) in both
      donors and recipients and evaluated the association between the polymorphism and
      risk of tumor recurrence. RESULTS: The donor TLR4 rs1927914 polymorphism was
      found to be significantly associated with HCC recurrence following LT. In
      multivariate logistic regression analysis, Milan criteria, microvascular invasion
      and donor TLR4 rs1927914 genotype were confirmed to be independent risk factors
      for HCC recurrence. Kaplan-Meier survival curves showed that patients carrying
      donors homozygous TT had a significantly lower recurrence-free survival and
      overall survival than CC/CT patients. Cox proportional hazards modeling indicated
      that TNM stage or Milan criteria, microvascular invasion, and donor TLR4
      rs1927914 genotype were independent factors for the clinical outcomes of LT
      patients. CONCLUSIONS: Donor TLR4 rs1927914 polymorphism is associated with an
      increased risk of HCC recurrence following LT and has a potential clinical value
      for the prediction of HCC recurrence after LT.

PMID- 29221802
TI  - Inflammation in the Prediction of Type 2 Diabetes and Hypertension in Healthy
      Adults.
AB  - BACKGROUND: While inflammation is associated with obesity and insulin resistance,
      their inter-relationships in the development of type 2 diabetes or hypertension
      are not clear. AIM OF THE STUDY: To evaluate inflammatory markers in prediction
      of type 2 diabetes and hypertension. METHODS: The study population of this
      retrospective cohort study consisted of individuals who participated in a
      comprehensive health screening program with measurement of white blood cell count
      and C-reactive protein from 2002-2010 (N = 96,606) in nondiabetic and
      normotensive Koreans. Median follow up time were 3.7 years for incident type 2
      diabetes and 3.3 years for hypertension. Multivariate Cox proportional hazards
      models were performed to assess risk for type 2 diabetes or hypertension by white
      blood cell or C-reactive protein quartiles with adjustment of various possible
      confounding factors including insulin resistance. RESULTS: During the follow-up
      period, 1448 (1.5%) developed type 2 diabetes and 10,405 (10.8%) developed
      hypertension. Among men, comparison of adjusted hazard ratios (HR) for incident
      type 2 diabetes in the highest versus lowest white blood cell or C-reactive
      protein quartiles were 1.48 [95% confidence interval (CI), 1.20-1.83] and 1.30
      (95% CI, 1.07-1.57), respectively. Among women, white blood cell but not C
      reactive protein was significantly associated with type 2 diabetes [HR 1.79 (95%
      CI 1.24-2.57)]. White blood cell and C-reactive protein quartiles were also
      modestly associated with incident hypertension in both sexes. CONCLUSIONS:
      Although white blood cell and C-reactive protein are associated with adiposity
      and insulin resistance, these inflammatory markers also independently predict
      type 2 diabetes and/or hypertension.

PMID- 29221803
TI  - Optimizing Non-Pharmacologic Management of Hypertriglyceridemia.
AB  - The cornerstone of initial management for hypertriglyceridemia (HTG) is lifestyle
      modification. The combination of weight loss through caloric restriction,
      alteration in macronutrient composition and increased energy expenditure reduces
      TG levels by approximately 50%. The addition of cinnamon, cacao products and
      isocaloric substitution of 1 serving of nuts may contribute another 5-15%
      lowering of TG. This can be particularly beneficial in patients with HTG who are
      at increased risk of cardiovascular disease.

PMID- 29221804
TI  - The Impact of the CD9 Tetraspanin on Lentivirus Infectivity and Exosome
      Secretion.
AB  - Efficient transduction tools are a hallmark for both research and therapy
      development. Here, we introduce new insights into the generation of lentiviral
      vectors with improved performance by utilizing producer cells with increased
      production rates of extracellular vesicles through CD9 overexpression. Most human
      cells secrete small vesicles from their surface (microvesicles) or intraluminal
      endosome-derived membranes (exosomes). In particular, enhanced levels of the
      tetraspanin CD9 result in significantly increased numbers of extracellular
      vesicles with exosome-like features that were secreted from four different human
      cell lines. Intriguingly, exosomes and their biogenesis route display
      similarities to lentivirus and we examined the impact of CD9 expression on
      release and infectivity of recombinant lentiviral vectors. Although the titers of
      released viral particles were not increased upon production in high CD9 cells, we
      observed improved performance in terms of both speed and efficiency of lentiviral
      gene delivery into numerous human cell lines, including HEK293, HeLa, SH-SY5Y, as
      well as B and T lymphocytes. Here, we demonstrate that enhanced CD9 enables
      lentiviral transduction in the absence of any pseudotyping viral glycoprotein or
      fusogenic molecule. Our findings indicate an important role of CD9 for lentiviral
      vector and exosome biogenesis and point out a remarkable function of this
      tetraspanin in membrane fusion, viral infectivity, and exosome-mediated
      horizontal information transfer.

PMID- 29221806
TI  - Characterization of Gene Alterations following Editing of the beta-Globin Gene
      Locus in Hematopoietic Stem/Progenitor Cells.
AB  - The use of engineered nucleases combined with a homologous DNA donor template can
      result in targeted gene correction of the sickle cell disease mutation in
      hematopoietic stem and progenitor cells. However, because of the high homology
      between the adjacent human beta- and delta-globin genes, off-target cleavage is
      observed at delta-globin when using some endonucleases targeted to the sickle
      mutation in beta-globin. Introduction of multiple double-stranded breaks by
      endonucleases has the potential to induce intergenic alterations. Using a novel
      droplet digital PCR assay and high-throughput sequencing, we characterized the
      frequency of rearrangements between the beta- and delta-globin paralogs when
      delivering these nucleases. Pooled CD34+ cells and colony-forming units from
      sickle bone marrow were treated with nuclease only or including a donor template
      and then analyzed for potential gene rearrangements. It was observed that, in
      pooled CD34+ cells and colony-forming units, the intergenic beta-delta-globin
      deletion was the most frequent rearrangement, followed by inversion of the
      intergenic fragment, with the inter-chromosomal translocation as the least
      frequent. No rearrangements were observed when endonuclease activity was
      restricted to on-target beta-globin cleavage. These findings demonstrate the need
      to develop site-specific endonucleases with high specificity to avoid unwanted
      gene alterations.

PMID- 29221807
TI  - Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of beta
      Hemoglobinopathies.
AB  - Although gene transfer to hematopoietic stem cells (HSCs) has shown therapeutic
      efficacy in recent trials for several individuals with inherited disorders,
      transduction incompleteness of the HSC population remains a hurdle to yield a
      cure for all patients with reasonably low integrated vector numbers. In previous
      attempts at HSC selection, massive loss of transduced HSCs, contamination with
      non-transduced cells, or lack of applicability to large cell populations has
      rendered the procedures out of reach for human applications. Here, we fused codon
      optimized puromycin N-acetyltransferase to herpes simplex virus thymidine kinase.
      When expressed from a ubiquitous promoter within a complex lentiviral vector
      comprising the betaAT87Q-globin gene, viral titers and therapeutic gene
      expression were maintained at effective levels. Complete selection and
      preservation of transduced HSCs were achieved after brief exposure to puromycin
      in the presence of MDR1 blocking agents, suggesting the procedure's suitability
      for human clinical applications while affording the additional safety of
      conditional suicide.

PMID- 29221805
TI  - Skeletal Muscle Regenerative Potential of Human MuStem Cells following
      Transplantation into Injured Mice Muscle.
AB  - After intra-arterial delivery in the dystrophic dog, allogeneic muscle-derived
      stem cells, termed MuStem cells, contribute to long-term stabilization of the
      clinical status and preservation of the muscle regenerative process. However, it
      remains unknown whether the human counterpart could be identified, considering
      recent demonstrations of divergent features between species for several somatic
      stem cells. Here, we report that MuStem cells reside in human skeletal muscle and
      display a long-term ability to proliferate, allowing generation of a clinically
      relevant amount of cells. Cultured human MuStem (hMuStem) cells do not express
      hematopoietic, endothelial, or myo-endothelial cell markers and reproducibly
      correspond to a population of early myogenic-committed progenitors with a
      perivascular/mesenchymal phenotypic signature, revealing a blood vessel wall
      origin. Importantly, they exhibit both myogenesis in vitro and skeletal muscle
      regeneration after intramuscular delivery into immunodeficient host mice.
      Together, our findings provide new insights supporting the notion that hMuStem
      cells could represent an interesting therapeutic candidate for dystrophic
      patients.

PMID- 29221808
TI  - A cannabinoid receptor antagonist attenuates ghrelin-induced activation of the
      mesolimbic dopamine system in mice.
AB  - Ghrelin has been attributed various physiological processes including food intake
      and reward regulation, through activation of the mesolimbic dopamine system.
      Reward modulation involves the mesolimbic dopamine system, consisting of the
      ventral tegmental area (VTA) dopamine neurons targeting nucleus accumbens (NAc),
      a system that ghrelin activates through VTA-dependent mechanisms. In the first
      study, we found that systemic intraperitoneal (ip) administration of rimonabant
      attenuated intracerebroventricular (icv) ghrelin's ability to cause locomotor
      stimulation and NAc dopamine release in mice. Ghrelin-induced (icv) chow intake
      was not altered by rimonabant administration (ip). Finally, we showed that
      bilateral VTA administration of rimonabant blocks the ability of intra-VTA
      administered ghrelin to increase locomotor activity, but does not affect food
      intake in mice. Collectively, these data indicate clear dissociation between
      regulation of food intake and activation of the mesolimbic dopamine system.

PMID- 29221809
TI  - Acute pain and peripheral sensitization following cautery disbudding in 1- and 4
      week-old calves.
AB  - Acute pain and peripheral sensitization development after cautery disbudding was
      investigated in 33 calves administered preventive multimodal analgesia. The
      animals were assigned randomly to three groups: 1) Group SH (Control), undergoing
      sham disbudding at 1 and 4weeks of age; 2) Group ED (Early Disbudding),
      undergoing disbudding at 1week of age and sham disbudding at 4weeks of age; 3)
      Group LD (Late Disbudding), undergoing sham disbudding at 1week of age and
      disbudding at 4weeks of age. Physiological parameters (heart rate, respiratory
      rate, rectal temperature, invasive blood pressure, cortisol, beta-endorphin,
      interleukin-1beta, interleukin-6, tumor necrosis factor-alpha and haptoglobin
      plasmatic concentration), local variables (tactile sensitivity score, pressure
      pain thresholds and horn temperature), behavior and pain scores [multidimensional
      pain scale and visual analogue scale (VAS)] were assessed at baseline and at
      several pre-determined time points until 24h after disbudding. Tactile
      sensitivity score significantly and equally increased in both groups ED and LD
      and pressure pain thresholds significantly decreased in group LD until 24h after
      disbudding compared to group SH. Pain and VAS scores significantly and equally
      increased in both groups ED and LD until 24h after disbudding compared to group
      SH. No significant differences in physiological parameters, behavior and horn
      temperature were detected among groups. The present study suggests that acute
      pain and peripheral sensitization develop and do not differ in calves disbudded
      at 1week and 4weeks of age. Moreover, the use of physiological and behavioral
      parameters as sole indicators of acute pain might lead to improper conclusions
      and should be reassessed.

PMID- 29221811
TI  - Matrix metalloproteinase functions in hepatic injury and fibrosis.
AB  - Liver fibrosis is the most common final outcome for chronic liver diseases. The
      complex pathogenesis includes hepatic parenchymal damage as a result of a
      persistent noxe, activation and recruitment of immune cells, activation of
      hepatic stellate cells, and the synthesis of fibrotic extracellular matrix (ECM)
      components leading to scar formation. Clinical studies and animal models
      demonstrated that fibrosis can be reversible. In this regard matrix
      metalloproteinases (MMPs) have been focused as therapeutic targets due to their
      ability to modulate tissue turnover during fibrogenesis as well as regeneration
      and, of special interest, due to their influence on cellular behavior like
      proliferation, gene expression, and apoptosis that, in turn, impact fibrosis and
      regeneration. The current review aims to summarize and update the knowledge about
      expression pattern and the central roles of MMPs in hepatic fibrosis.

PMID- 29221812
TI  - Role of immune cells in crystal-induced kidney fibrosis.
AB  - Chronic kidney diseases can lead to kidney fibrosis, which can be considered a
      futile attempt of tissue healing to replaces functional kidney tissue with
      connective tissue, basically forming a scar. Chronic inflammation is a frequent
      cause of kidney fibrosis. Classical as well as recently discovered immune cell
      subsets and their molecular mediators have been intensively investigated for
      their contribution to kidney fibrosis and their potential as therapeutic targets.
      Here we review the current knowledge about the role of immune cells in crystal
      induced renal fibrosis.

PMID- 29221810
TI  - Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in
      chronic inflammatory diseases.
AB  - Inflammation represents a comprehensive host response to external stimuli for the
      purpose of eliminating the offending agent, minimizing injury to host tissues and
      fostering repair of damaged tissues back to homeostatic levels. In normal
      physiologic context, inflammatory response culminates with the resolution of
      infection and tissue damage response. However, in a pathologic context,
      persistent or inappropriately regulated inflammation occurs that can lead to
      chronic inflammatory diseases. Recent scientific advances have integrated the
      role of innate immune response to be an important arm of the inflammatory
      process. Accordingly, the dysregulation of innate immunity has been increasingly
      recognized as a driving force of chronic inflammatory diseases. Mitochondria have
      recently emerged as organelles which govern fundamental cellular functions
      including cell proliferation or differentiation, cell death, metabolism and
      cellular signaling that are important in innate immunity and inflammation
      mediated diseases. As a natural consequence, mitochondrial dysfunction has been
      highlighted in a myriad of chronic inflammatory diseases. Moreover, the
      similarities between mitochondrial and bacterial constituents highlight the
      intrinsic links in the innate immune mechanisms that control chronic inflammation
      in diseases where mitochondrial damage associated molecular patterns (DAMPs) have
      been involved. Here in this review, the role of mitochondria in innate immune
      responses is discussed and how it pertains to the mitochondrial dysfunction or
      DAMPs seen in chronic inflammatory diseases is reviewed.

PMID- 29221813
TI  - Neonatal programming with testosterone propionate reduces dopamine transporter
      expression in nucleus accumbens and methylphenidate-induced locomotor activity in
      adult female rats.
AB  - Research in programming is focused on the study of stimuli that alters sensitive
      periods in development, such as prenatal and neonatal stages, that can produce
      long-term deleterious effects. These effects can occur in various organs or
      tissues such as the brain, affecting brain circuits and related behaviors. Our
      laboratory has demonstrated that neonatal programming with sex hormones affects
      the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine
      (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response
      to psychostimulant drugs such as methylphenidate and the possible mechanism(s)
      involved have not been studied in adult rats exposed to sex hormones during the
      first hours of life. Thus, the aim of this study was to examine the locomotor
      activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA
      transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone
      propionate (TP: 1mg/50MULs.c.) or estradiol valerate (EV: 0.1mg/50MULs.c.) at
      postnatal day 1. Our results demonstrated that adult female rats treated with TP
      have a lower methylphenidate-induced locomotor activity compared to control and
      EV-treated adult female rats. This reduction in locomotor activity is related
      with a lower NAcc DAT expression. However, neither methylphenidate-induced
      locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult
      male rats. Our results suggest that early exposure to sex hormones affects long
      term dopaminergic brain areas involved in the response to psychostimulants, which
      could be a vulnerability factor to favor the escalating doses of drugs of abuse.

PMID- 29221814
TI  - Use of interventional radiology as initial hemorrhage control to improve outcomes
      for potentially lethal multiple blunt injuries.
AB  - INTRODUCTION: Recently, trauma management has been markedly improved with
      interventional radiology (IVR) and damage-control strategies. However, the
      indications for its use in hemodynamically unstable patients with severe trauma
      remains unclear. In some cases, IVR may be more effective than surgery for damage
      control hemostasis; however, performing IVR in life-threatening trauma settings
      is challenging. To address this, we practiced and evaluated a trauma-management
      system with emergency physicians who trained for both severe trauma management,
      and techniques of surgery and IVR. MATERIALS AND METHODS: Among the 1822 patients
      with severe trauma admitted between October 2014 and December 2016, 201 underwent
      emergency surgery or IVR. Among these, 16 patients whose systolic blood pressure
      was <=90 mmHg, without improvement following primary resuscitation, and whose
      first intervention was IVR, were analyzed. We retrospectively evaluated the
      admission characteristics, IVR-related characteristics, and prognoses, and
      compared several parameters before and after IVR. RESULTS: This study included 10
      men and 6 women (median age: 46 years). IVR was performed for 10 pelvic
      fractures; five liver-, one splenic-, and one renal injury; and one transection
      each of the external carotid-, vertebral-, axillosubclavian-, intercostal-, and
      lumbar arteries. The mean times from the patient arrival, and diagnosis to the
      start of IVR were 56.3 +/- 26.6 and 15.1 +/- 3.8 min, respectively. The mean time
      spent in the angiography suite was 50 min. The systolic blood pressure, pulse
      rate, base excess/deficit, serum-lactate levels, and D-dimer values were
      significantly improved after IVR. Although two patients needed additional
      treatment for morbidities following IVR intervention, all achieved complete
      recovery. The mortality rate was 25.0%, and no preventable deaths were noted.
      Eight patients showed unexpected survival. CONCLUSIONS: In some cases, IVR may be
      the best first measure for resuscitative hemostasis in potentially lethal
      multiple injuries, given efficient diagnoses/actions and the ability to deal with
      complications.

PMID- 29221816
TI  - Reply.

PMID- 29221815
TI  - Corneal confocal microscopy as a non-invasive test to assess diabetic peripheral
      neuropathy.
AB  - OBJECTIVE: To evaluate the efficacy of corneal confocal microscopy (CCM) as a non
      invasive test to assess diabetic peripheral neuropathy in Chinese patients
      diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Diabetic distal
      symmetric polyneuropathy (DSPN) and its severity degrees were assessed based on
      the modified Toronto diagnostic criteria in 128 patients with type 2 diabetes (No
      DSPN [n = 49], mild DSPN [n = 43], moderate-to-severe DSPN [n = 36]) and 24 age
      matched controls. CCM was also examined in all enrolled subjects. Corneal nerve
      fiber length (CNFL), corneal nerve branch density (CNBD) and corneal nerve fiber
      density (CNFD) were analyzed by Fiji imaging analysis software. The efficacy of
      CCM as a non-invasive test to assess diabetic peripheral neuropathy was
      determined. RESULTS: CNFL was 17.99 +/- 0.66, 15.82 +/- 0.64, 14.98 +/- 0.63, and
      12.49 +/- 0.93 in healthy controls, T2DM patients with no, mild, and moderate-to
      severe DPN, respectively. CNFL in type 2 diabetes patients with no, mild, and
      moderate-to-severe DSPN demonstrated a significant reduction than in healthy
      controls (P = .012, .003 and <.001, respectively). CNFL in patients with moderate
      to-severe DSPN was significantly shorter than in patients with no or mild DSPN (P
      < .001 and .004, respectively). CNBD was 41.48 +/- 3.35, 33.02 +/- 2.50, 30.91 +/
      2.33, and 18.00 +/- 2.33 in healthy controls, T2DM patients with no, mild, and
      moderate-to-severe DPN, respectively. CNBD in healthy control was significantly
      higher than in type 2 diabetes patients with no, mild, and moderate-to-severe
      DSPN (P = .036, 0.016 and < .001, respectively). CNBD in patients with moderate
      to-severe DSPN was significantly lower than in patients with no or mild DSPN (P <
      .001 for both). CNFD was 35.32 +/- 1.18, 35.68 +/- 1.10, 34.54 +/- 1.12, and
      32.28 +/- 1.76 in healthy controls, T2DM patients with no, mild, and moderate-to
      severe DPN, respectively. CNFD did not differ among the four groups. In an
      analysis that divided CNFL, CNFD and CNBD into quartiles, there were no
      significant differences in electromyography findings and vibration perception
      threshold among the 4 groups; however, significant differences were seen in the
      positive distribution of temperature perception measurements following CNFL and
      CNBD stratification (P = .001 and < .001, respectively). CONCLUSION: CCM might be
      a non-invasive method for detecting DSPN and its severity degree in Chinese
      patients diagnosed with type 2 diabetes.

PMID- 29221817
TI  - Polyunsaturated fatty acids in plasma at 8 years and subsequent allergic disease.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the
      risk of allergic disease. However, evidence from previous studies is
      inconclusive, and limited longitudinal data exist using circulating biomarkers of
      PUFA intake and metabolism. OBJECTIVE: We aimed to investigate associations
      between n-3 and n-6 PUFAs at age 8 years and asthma, rhinitis, and aeroallergen
      sensitization at age 16 years. METHODS: Proportions of n-3 PUFAs (very long-chain
      n-3 [VLC n-3; sum of eicosapentaenoic acid, docosapentaenoic acid, and
      docosahexaenoic acid] and alpha-linolenic acid) and n-6 PUFAs (linoleic acid and
      arachidonic acid [AA]) in blood samples at age 8 years were measured for 940
      children from the prospective Swedish birth cohort BAMSE (Children, Allergy,
      Milieu, Stockholm, Epidemiology). Allergic disease phenotypes were defined by
      using questionnaires and IgE measures at the ages of 8 and 16 years. Logistic
      regression was used to examine potential associations. RESULTS: A higher
      proportion of total VLC n-3 PUFAs in plasma at age 8 years was associated with a
      reduced risk of prevalent asthma, rhinitis, and aeroallergen sensitization at age
      16 years and with incidence of asthma between 8 and 16 years (adjusted odds
      ratio, 0.67; 95% CI, 0.47-0.94). AA was associated with a reduced risk of asthma,
      aeroallergen sensitization, and allergic rhinitis. The findings were most evident
      for allergic phenotypes of asthma and rhinitis. Additionally, AA was associated
      with an increased probability of asthma and rhinitis remission between 8 and 16
      years of age. CONCLUSION: Higher proportions of certain VLC n-3 and very long
      chain n-6 PUFAs in plasma phospholipids at age 8 years were associated with a
      reduced risk of allergic disease at age 16 years.

PMID- 29221818
TI  - Chronic obstructive pulmonary disease exacerbation frequency and serum IgG
      levels.

PMID- 29221819
TI  - Cerebellar alterations in a model of Down syndrome: The role of the Dyrk1A gene.
AB  - Down syndrome (DS) is characterized by a marked reduction in the size of the
      brain and cerebellum. These changes play an important role in the motor
      alterations and cognitive disabilities observed in this condition. The Ts65Dn
      (TS) mouse, the most commonly used model of DS, reflects many DS phenotypes,
      including alterations in cerebellar morphology. One of the genes that is
      overexpressed in both individuals with DS and TS mice is DYRK1A/Dyrk1A (dual
      specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which has been
      implicated in the altered cerebellar structural and functional phenotypes
      observed in both populations. The aim of this study was to evaluate the effect of
      Dyrk1A on different alterations observed in the cerebellum of TS animals. TS mice
      were crossed with Dyrk1A +/- KO mice to obtain mice with a triplicate segment of
      Mmu16 that included Dyrk1A (TS +/+/+), mice with triplicate copies of the same
      genes that carried only two copies of Dyrk1A (TS +/+/-), euploid mice that
      expressed a normal dose of Dyrk1A (CO +/+) and CO animals with a single copy of
      Dyrk1A (CO +/-). Male mice were used for all experiments. The normalization of
      the Dyrk1A gene dosage did not rescue the reduced cerebellar volume. However, it
      increased the size of the granular and molecular layers, the densities of
      granular and Purkinje cells, and dendritic arborization. Furthermore, it improved
      the excitatory/inhibitory balance and walking pattern of TS +/+/- mice. These
      results support the hypothesis that Dyrk1A is involved in some of the structural
      and functional cerebellar phenotypes observed in the TS mouse model.

PMID- 29221820
TI  - Early Response to Intravitreal Dexamethasone Implant Therapy in Diabetic Macular
      Edema May Predict Visual Outcome.

PMID- 29221821
TI  - Reply.

PMID- 29221822
TI  - Impacts of Implantable Collamer Lens V4c Placement on Angle Measurements Made by
      Optical Coherence Tomography: Two-Year Follow-up.

PMID- 29221823
TI  - Repeatability and Agreement of Orbscan II, Pentacam HR, and Galilei Tomography
      Systems in Corneas With Keratoconus.

PMID- 29221824
TI  - Early Trabeculotomy Ab Externo in the Treatment of Sturge-Weber Syndrome.

PMID- 29221825
TI  - Tuberculosis and immigration.
AB  - Tuberculosis continues to be a major public health problem in Spain. The
      incidence of tuberculosis in the native population has declined steadily in
      recent years. Migration flows have changed drastically since the beginning of the
      21st century, with Spain becoming a recipient country for immigrants. Because
      most of the immigrants comes from countries with high incidence of tuberculosis,
      the contribution of the migrant population to new cases of tuberculosis is higher
      in relative terms than its weight in the total population. Tuberculosis programs
      must address the cultural, economic and medical aspects of the disease, and
      particularly target groups at risk, including the migrant population. In this
      paper, we will review the epidemiology and dynamics of tuberculosis in the
      migrant population, their differentiating clinical characteristics and the
      programmatic actions to address the problem.

PMID- 29221826
TI  - Trends of invasive pneumococcal disease and its serotypes in the Autonomous
      Community of Madrid.
AB  - INTRODUCTION: Streptococcus pneumoniae is an important cause of morbidity.
      Vaccination is the most effective measure to prevent it. The aim of this study is
      to analyse the evolution of invasive pneumococcal disease (IPD). MATERIAL AND
      METHODS: Observational study of IPD cases notified to the Epidemiological
      Surveillance Network of the Autonomous Community of Madrid between 2008 and 2015.
      The IPD case was defined as the disease caused by Streptococcus pneumoniae, with
      isolation and DNA or antigen detection, in samples from normally sterile sites.
      The isolated strains were sent to the Regional Public Health Laboratory for
      identification of the serotype. Serotypes were classified according to their
      inclusion in the 7-valent conjugate vaccine (PCV7), in the 13-valent vaccine, but
      not in the 7-valent vaccine (PCV13-additional) and not included in the 13-valent
      vaccine (non-PCV). The Incidence Rate Ratios (IRRs) were calculated comparing the
      2011-2012 and 2013-2015 periods with the 2008-2010 period. RESULTS: 4,307 cases
      were reported. 86.6% were serotyped. The IRR of IPD was 0.67 and 0.67 for all
      serotypes; 0.43 and 0.45 for PCV7 serotypes; 0.46 and 0.25 for PCV13-additional
      serotypes, and 1.01 and 1.32 for non-PCV13 serotypes in the 2011-2012 and 2013
      2015 periods. The incidence of serotypes 8, 9N, 10A, 23B, 24F and serogroup 33
      increased significantly in the 2013-2015 period. Serotypes 15B and 24F accounted
      for 24% of non-PCV13 cases in children under 5years, serotypes 8 and 9N for 51%
      in the population aged 5 to 59years and serotypes 8 and 22F for 25% in the
      population aged over 59years. CONCLUSIONS: The incidence of serotypes not
      included in conjugate vaccines has increased, especially in children under
      5years, but the total incidence of IPD has decreased. It is important to continue
      with the epidemiological and microbiological surveillance programmes to assess
      the effect of vaccination on the incidence of IPD.

PMID- 29221827
TI  - Prevalence of COPD in 6 Urban Clusters in Argentina: The EPOC.AR Study.
AB  - INTRODUCTION: The prevalence of chronic obstructive pulmonary disease (COPD) has
      not been studied in Argentina. OBJECTIVES: To determine the prevalence and
      relevant clinical characteristics of COPD in a representative sample. MATERIAL
      AND METHODS: We performed a cross-sectional study in a population of adults aged
      >= 40 years randomly selected by cluster sampling in 6 urban locations. Subjects
      answered a structured survey and performed pre- and post-bronchodilator
      spirometry (PBD). COPD was defined as FEV1/FVC ratio < 0.7 predicted value. The
      total prevalence was estimated for each cluster with its 95% confidence interval
      (CI). RESULTS: Of 4,599 surveys and 3,999 spirometries, 3,469 were considered of
      adequate quality (86.8%) for our study. The prevalence of COPD was 14.5% (CI:
      13.4-15.7). The distribution of COPD cases according to FEV1 (GOLD 2017) was
      stage 1: 38% (CI: 34-43); stage 2: 52% (CI: 47-56); stage 3: 10% (CI: 7-13); and
      stage 4: 1% (CI: 0-2), and according to the refined ABCD (GOLD 2017) assessment:
      A: 52% (CI: 47-56); B: 43% (CI: 39-48); C: 1% (CI: 0-2); D: 4% (CI: 2-6). The
      rate of underdiagnosis was 77.4% (CI 73.7-81.1%) and diagnostic error 60.7% (CI
      55.1-66.3%). A significant association was found between COPD and age (OR 3.77 in
      individuals 50-59 years of age and 19.23 in those > 80 years), male gender (OR
      1.62; CI 1.31-2), smoking (OR 1.95; CI 1.49-2.54), low socioeconomic status (OR
      1.33; CI 1.02-1.73), and previous tuberculosis (OR 3.3; CI 1.43-7.62).
      CONCLUSIONS: We estimate that more than 2.3 million Argentineans have COPD, with
      high rates of underdiagnosis and diagnostic error.

PMID- 29221828
TI  - Long-Term Acquired Bronchoesophageal Fistula.

PMID- 29221829
TI  - Constitutive expression of the active fragment of human vasostatin Vs30 in Pichia
      pastoris SMD1168H.
AB  - Vasostatin 30 (Vs30) is an active fragment derived from the N-terminal region
      (135-164 aa) of human calreticulin and has the ability to inhibit angiogenesis.
      In this work, the expression of Vs30 was performed using a protease-deficient
      strain of the methylotrophic yeast Pichia pastoris. The vs30 gene was optimized
      for P. pastoris preferential codon usage and inserted into constitutive
      expression vector pGAPZalphaA. In addition, a plasmid with four copies of the
      expression cassette was obtained and transformed into P. pastoris. The flask
      fermentation conditions were: culture volume of 25 mL in 250 mL baffled flasks at
      28  degrees C, pH 6 and harvest time of 48 h. Up to 21.07 mg/L Vs30 were attained
      and purified by ultrafiltration with a 30-kDa cut-off membrane and the recovery
      was 49.7%. Bioactivity of Vs30 was confirmed by the inhibition of cell
      proliferation, as well as the inhibition of the capillary-like structures
      formation of EA.hy926 cells in vitro. This work constitutes the first report on
      the expression of Vs30 in Pichia pastoris using a constitutive promoter and multi
      copy approach such as strategies to improve the recombinant Vs30 expression.

PMID- 29221830
TI  - Distinguishable memory retrieval networks for collaboratively and non
      collaboratively learned information.
AB  - Learning often occurs in communicative and collaborative settings, yet almost all
      research into the neural basis of memory relies on participants encoding and
      retrieving information on their own. We investigated whether learning linguistic
      labels in a collaborative context at least partly relies on cognitively and
      neurally distinct representations, as compared to learning in an individual
      context. Healthy human participants learned labels for sets of abstract shapes in
      three different tasks. They came up with labels with another person in a
      collaborative communication task (collaborative condition), by themselves
      (individual condition), or were given pre-determined unrelated labels to learn by
      themselves (arbitrary condition). Immediately after learning, participants
      retrieved and produced the labels aloud during a communicative task in the MRI
      scanner. The fMRI results show that the retrieval of collaboratively generated
      labels as compared to individually learned labels engages brain regions involved
      in understanding others (mentalizing or theory of mind) and autobiographical
      memory, including the medial prefrontal cortex, the right temporoparietal
      junction and the precuneus. This study is the first to show that collaboration
      during encoding affects the neural networks involved in retrieval.

PMID- 29221831
TI  - Processing of implicit versus explicit predictive contextual information in
      Parkinson's disease.
AB  - We investigated the effects of implicit versus explicit local contextual
      processing in Parkinson's disease (PD) using electrophysiological measures. EEG
      recording blocks consisted of targets preceded by either randomized sequences of
      standards or by sequences including a predictive sequence signaling the
      occurrence of a target event. PD patients ("on" medication) and healthy controls
      performed two sessions: in the first the regularity of the predictive sequence
      was implicit, while in the second this regularity was made explicit. PD and
      control subjects showed shorter reaction times for predicted versus random
      targets across both the implicit and explicit sessions. Healthy controls showed a
      facilitation of the P3b latency for predicted targets (compared with random
      targets) in both the implicit and explicit sessions, while PD patients showed no
      significant P3b latency differences between the two target conditions across both
      sessions. In healthy controls the P3b amplitude of the last most-informative
      stimulus of the predictive sequence (n-1) was larger in the explicit compared to
      the implicit session, while this difference was absent in PD patients. Functional
      connectivity measures showed that during the explicit and implicit sessions
      detection of n-1 was associated with higher gamma values and weaker fronto
      central-parietal connections, in the theta band, in PD compared to controls. The
      findings suggest that implicit and explicit processing of predictive contextual
      information is altered in PD patients and that this may be associated with
      functional connectivity abnormalities within top-down frontal networks.

PMID- 29221832
TI  - Detecting our own vocal errors: An event-related study of the thresholds for
      perceiving and compensating for vocal pitch errors.
AB  - Previous studies suggest that a perception-action dissociation exists for the
      cortical processing of vocal pitch, because speakers compensate for small vocal
      errors without awareness. In this event-related potential (ERP) study,
      participants vocalized while hearing their productions either altered or
      unaltered in pitch, and reported whether their auditory feedback was altered.
      Pitch alterations as small as 10 cents resulted in compensatory vocal responses,
      while participants reported hearing perturbations that were 15 cents and larger.
      Similarly, P1 ERP responses were elicited by perturbations 15 cents and larger,
      while N1 responses followed a linear trend with increasing perturbation
      magnitudes, and P2 responses were elicited by perturbations 30 cents and larger.
      Although their thresholds differed, both motor and perceptual responses were
      elicited by small frequency altered feedback (FAF) perturbations. Previous
      reports of a perception-action dissociation may reflect differences in the
      magnitude of vocal error required to elicit a motor response, and for an
      individual to report a pitch change, rather than to detect a pitch change (as
      reflected by ERP responses).

PMID- 29221833
TI  - Giving others the option of choice: An fMRI study on low-cost cooperation.
AB  - Successful social relationships require a consideration of a partner's thoughts
      and intentions. This aspect of social life is captured in the social mindfulness
      paradigm (SoMi task), in which participants make decisions that either limit or
      preserve options for their interaction partner's subsequent choice. Here we
      investigated the neural correlates of spontaneous socially mindful and unmindful
      behaviours. Functional magnetic resonance data were acquired from 47 healthy
      adolescents and young adults (age 16-27) as they completed the SoMi task. Being
      faced with socially relevant choices was associated with activity in the medial
      prefrontal cortex, anterior cingulate, caudate, and insula, which is consistent
      with prior neuroeconomical research. Importantly, socially mindful choices were
      associated with activity in the right parietal cortex and the caudate, whereas
      unmindful choices were associated with activity in the left prefrontal cortex.
      These neural findings were consistent with the behavioural preference for mindful
      choices, suggesting that socially mindful decisions are the basic inclination,
      whereas socially unmindful responses may require greater effort and control.
      Together, these results begin to uncover the neural correlates of socially
      mindful and unmindful choices, and illuminate the psychological processes
      involved in cooperative social behaviour.

PMID- 29221834
TI  - Emotion and sex of facial stimuli modulate conditional automaticity in behavioral
      and neuronal interference in healthy men.
AB  - Our surrounding provides a host of sensory input, which we cannot fully process
      without streamlining and automatic processing. Levels of automaticity differ for
      different cognitive and affective processes. Situational and contextual
      interactions between cognitive and affective processes in turn influence the
      level of automaticity. Automaticity can be measured by interference in Stroop
      tasks. We applied an emotional version of the Stroop task to investigate how
      stress as a contextual factor influences the affective valence-dependent level of
      automaticity. 120 young, healthy men were investigated for behavioral and brain
      interference following a stress induction or control procedure in a counter
      balanced cross-over-design. Although Stroop interference was always observed, sex
      and emotion of the face strongly modulated interference, which was larger for
      fearful and male faces. These effects suggest higher automaticity when processing
      happy and also female faces. Supporting behavioral patterns, brain data show
      lower interference related brain activity in executive control related regions in
      response to happy and female faces. In the absence of behavioral stress effects,
      congruent compared to incongruent trials (reverse interference) showed little to
      no deactivation under stress in response to happy female and fearful male trials.
      These congruency effects are potentially based on altered context- stress-related
      facial processing that interact with sex-emotion stereotypes. Results indicate
      that sex and facial emotion modulate Stroop interference in brain and behavior.
      These effects can be explained by altered response difficulty as a consequence of
      the contextual and stereotype related modulation of automaticity.

PMID- 29221835
TI  - Impact of surgical approach and patient factors on Hospital Consumer Assessment
      of Healthcare Providers and Systems (HCAHPS) survey scoring in gynecologic
      surgery.
AB  - OBJECTIVE: We sought to compare the Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) survey responses of women who underwent
      gynecologic surgery at our institution across patient factors and surgical
      approach. METHODS: We identified patients with returned HCAHPS surveys following
      an inpatient laparoscopic surgery or laparotomy in gynecologic surgery from
      10/1/2012-9/30/2015. Exclusions included patient age<18years, discharge by a
      service other than Gynecologic Surgery, or refusal of Minnesota research
      authorization. HCAHPS composite measures were calculated using published top-box
      and summary star rating methodologies and dichotomized as "high" versus "low."
      Chi-square, Fisher's exact, and Wilcoxon rank sum tests, and multivariable
      logistic regression were performed. RESULTS: Of 403 women who met inclusion
      criteria, 109 (27%) underwent laparoscopic surgery (19% laparoscopic hysterectomy
      and 8% other laparoscopic procedures) and 294 (73%) laparotomy (28% open
      hysterectomy and 47% other open procedures). Length of stay (LOS) was longer for
      laparotomy cases vs. laparoscopy cases (median 2.5days following open
      hysterectomy and 4days following other open procedures vs 1day following
      laparoscopic hysterectomy and other laparoscopic procedures, p<0.001). Patients
      who underwent laparotomy other than hysterectomy were more likely to have low
      summary scores (79% vs 66% laparoscopic hysterectomy, 66% open hysterectomy, and
      52% other laparoscopic procedures, p=0.005). After adjustment, non-hysterectomy
      laparotomy cases were more likely to have a low summary score than non
      hysterectomy laparoscopy (OR 3.86, 95% CI 1.71-8.68, p=0.001). This significance
      did not remain after further adjusting for LOS. CONCLUSION: In Gynecologic
      Surgery, patients undergoing laparotomy gave lower hospital ratings compared to
      laparoscopy. Those with longer LOS reported poorer patient experience, which is
      the driving variable for lower scores. In the future, it may be necessary to
      adjust for surgical approach when reporting patient experience scoring.

PMID- 29221836
TI  - Efficacy versus Complications in Arterial Thrombolysis.
AB  - BACKGROUND: Acute peripheral arterial occlusions threaten life and limb.
      Thrombolysis is an established, minimally invasive alternative treatment for
      surgical thromboembolectomy. Yet, there is no consensus regarding an optimal
      thrombolysis protocol, and current knowledge is largely based on studies from the
      1990s. This study reviews a contemporary cohort of patients treated with
      thrombolysis and aims to evaluate the treatment results and to identify possible
      predictors for outcome and (bleeding) complications. METHODS: The electronic
      health record data of all consecutive patients who underwent thrombolysis for
      acute limb ischemia due to thromboembolic lower extremity arterial occlusions
      between April 2006 and June 2012 were analyzed. End points were change in
      clinical stage of ischemia, incidence of bleeding complications, duration of
      thrombolysis, predictors of outcome and complications, and mortality and
      amputation-free rates after 30-day and 6-months follow-up. RESULTS: In total, 109
      cases were included. Clinical improvement was observed in 79%. Amputation-free
      rates at 30 days and 6 months were 94% and 90%, respectively. The incidence of
      major bleeding complications was 13%. Median duration of thrombolysis was 27 (4
      68) hr. Mortality rates at 30 days and 6 months were 7% and 16%, respectively;
      none bleeding related. In addition to age, popliteal artery occlusions and a
      progressed chronic vascular stage are predictive for a worse outcome. Age, female
      sex, and cardiac history were risk factors for bleeding. CONCLUSIONS: Treatment
      of peripheral arterial occlusions with high-dose thrombolysis on an intensive
      care unit yields high clinical success rates, but major bleeding complications
      are often observed. Strict clinical observation remains essential since intensive
      monitoring of hemostatic parameters during thrombolysis does not predict bleeding
      complications.

PMID- 29221837
TI  - A Single-Center Retrospective Analysis of the Efficacy of a New Balloon Catheter
      in Autogenous Arteriovenous Fistula Dysfunction Resistant to Conventional Balloon
      Angioplasty.
AB  - PURPOSE: The purpose of the study was to present a new alternative balloon
      catheter option for autogenous arteriovenous fistula (AVF) dysfunction with a
      stiff constriction resistant to conventional balloon angioplasty. METHODS: Our
      first series of 51 patients with autogenous AVF dysfunction who were
      simultaneously treated with VascuTrakTM balloon catheter, following failed
      conventional balloon therapy (failure was defined as residual stenosis of >30%),
      were retrospectively observed and analyzed. The indices that were used to
      evaluate the clinical efficacy of VascuTrak balloon catheter included the
      immediate technical success rate, residual stenosis, successful dilation times,
      degree of pain assessed using the Visual Analog Scale, complications, and follow
      up patency rate. RESULTS: The stenotic or occlusive lesions of all 51 cases
      resistant to conventional balloon angioplasty were promptly eliminated or
      alleviated (residual stenosis rate <= 30%), with a 100% immediate technical
      success rate. VascuTrak balloon catheters were successful in achieving full
      dilation under working pressure, of which 44 cases required a 1-time dilation
      (86.3%) and 7 cases required 2 dilations, which differed significantly from the
      average of 2.4 dilations required by the preceding conventional balloon therapy
      (P < 0.0001). A statistically significant improvement in the degree of pain
      experienced by patients who received VascuTrak balloon dilation was observed
      compared to that of the preceding conventional balloon dilation (P < 0.0001). One
      case of a brachial artery pseudoaneurysm complication occurred in the
      perioperative period. The primary patency rate was 88.2% at 6 months and 74.5% at
      12 months. CONCLUSION: The use of VascuTrak balloon catheter to treat autogenous
      AVF dysfunction resistant to conventional balloon angioplasty appears to be safe
      and effective, although further, large randomized controlled trials are
      necessary.

PMID- 29221838
TI  - Aneurysm of the Anomalous Splenic Artery Arising from Superior Mesenteric Artery
      Treated by Coil Embolization: A Report of Two Cases and Literature Review.
AB  - BACKGROUND: Aneurysm of splenic artery (SA) which arises from the superior
      mesenteric artery (SMA) is a very rare condition. The aim of this study was to
      present our experience with 2 such patients treated by coil embolization.
      METHODS: A 33-year-old man and a 61-year-old woman were incidentally identified
      with aneurysms of the SA which arose from the SMA. Endovascular therapy of coil
      embolization was chosen to treat the aneurysm. RESULTS: Follow-up computed
      tomography showed no change in the location of the coils and occlusion of
      majority of the aneurysm sac. The 2 patients have been doing well during a 26
      month and 10-month follow-up period, respectively. CONCLUSIONS: Combined with the
      experience of the previous literature, we think coil embolization can be cost
      effective and minimally invasive in selected cases, depending on the morphology
      and site of the lesion.

PMID- 29221839
TI  - Cementless One-Stage Revision in Chronic Periprosthetic Hip Joint Infection.
      Ninety-One Percent Infection Free Survival in 56 Patients at Minimum 2-Year
      Follow-Up.
AB  - BACKGROUND: Cementless 1-stage revision in chronic periprosthetic hip joint
      infections is limited evaluated. The purpose of this study was to evaluate a
      specific treatment protocol in this patient group. METHODS: The study was
      performed as a multicenter, proof-of-concept, observational study with
      prospective data collection. Patients were treated with a cementless 1-stage
      revision according to the CORIHA protocol between 2009 and 2014. Fifty-six
      patients, McPherson type III-A/B-1/2, were enrolled with a mean follow-up time
      from the CORIHA procedure of 4 years (minimum of 2 years). The primary outcome
      was re-revision performed due to infection and was evaluated by competing risk
      analysis, with death and aseptic revision as competing events. All-cause
      mortality was evaluated by Kaplan-Meier survival analysis. Oxford Hip Score (OHS)
      was used as disease-specific patient-reported outcome measure. RESULTS: The
      cumulative incidence of re-revision due to infection was 8.9% (confidence
      interval [CI] 3.2%-18.1%). The 1-year and 5-year survival incidence was 96% (CI
      86%-99%) and 89% (CI 75%-95%). OHS at baseline was 19.9 (CI 17.3-22.6) and at 24
      month follow-up 35.1 (CI 31.7-38.5). The mean change in OHS from baseline to 24
      month follow-up was 11.8 points (CI 7.3; 16.3). Three patients had aseptic
      revision performed: two suffered periprosthetic fractures and one had stem
      subsidence. Failure analysis of the 5 reinfections did not detect a clear pattern
      as to the cause of failure. CONCLUSION: We found that cementless 1-stage revision
      in chronic periprosthetic hip joint infections has low reinfection rates in
      selected patients and may be applicable as a first-line treatment.

PMID- 29221841
TI  - Risk Factors for Reaching the Post-Operative Transfusion Trigger in a Community
      Primary Total Knee Arthroplasty Population.
AB  - BACKGROUND: Little data exist to evaluate an individual's pre-operative risk of
      blood transfusion following total knee arthroplasty (TKA). Our aim is to identify
      the risk factors associated with reaching the transfusion trigger of Hb <8 g/dL
      (TT8) following surgery and how perioperative tranexamic acid (TXA) affects that
      outcome. METHODS: Using a retrospective cohort study design, routine, unilateral
      TKAs performed between 2011 and 2013 in 19 hospitals were reviewed. Patients
      hospitalized <=1 day or >=4 days were excluded. Demographic data, clinical
      characteristics, and potential confounders were included in statistical models.
      Data were abstracted from electronic clinical and utilization databases. The main
      outcome was the risk of reaching the TT8. The primary exposure was use of single
      dose intravenous TXA. Logistic regression was used to model the adjusted
      association between TXA usage and post-operative risk of reaching TT8. RESULTS: A
      total of 10,518 TKAs met criteria; 2566 (24.3%) received TXA (+TXA). The
      proportion that reached the TT8 was 2.1% for + TXA and 5.3% for -TXA (P < .0001).
      Pre-operative Hb levels were associated with increasing odds of reaching the TT8.
      Increasing age was weakly associated with this outcome. The odds of reaching the
      TT8 were lower for patients who had received TXA, had increasing body mass index,
      and surgical duration in the third quartile. CONCLUSION: Not receiving TXA within
      24 hours of TKA and pre-operative Hb levels <13 g/dL were independently
      associated with the odds of reaching the post-operative TT8 following a primary
      TKA.

PMID- 29221840
TI  - A Multicenter Study of Irrigation and Debridement in Total Knee Arthroplasty
      Periprosthetic Joint Infection: Treatment Failure Is High.
AB  - BACKGROUND: In total knee arthroplasty (TKA) periprosthetic joint infection
      (PJI), irrigation and debridement (I&D) with component retention is a treatment
      option with a wide variation in reported failure rates. The purpose of this study
      was to determine failure rates, outcomes, and factors that predict failure in I&D
      for TKA PJI. METHODS: A multicenter observational study of patients with a TKA
      PJI and subsequently undergoing an I&D with retention of components was
      conducted. The primary outcome was failure rate of I&D, where failure was defined
      as any subsequent surgical procedures. RESULTS: Two hundred sixteen cases of I&D
      with retention of components performed on 206 patients met inclusion criteria.
      The estimated long-term failure rate at 4 years was 57.4%. Time-to-event analyses
      revealed that the median survival time was 14.32 months. Five-year mortality was
      19.9%. Multivariable modeling revealed that time symptomatic and organism were
      independent predictors of I&D failure. Culture-negative status had a higher
      hazard for failure than culture-positive patients. When primary organism and time
      symptomatic were selected to produce an optimized scenario for an I&D, the
      estimated failure rate was 39.6%. CONCLUSION: I&D with retention of components
      has a high failure rate, and there is a high incidence of more complex procedures
      after this option is chosen. The patient comorbidities we investigated did not
      predict I&D success. Our results suggest that I&D has a limited ability to
      control infection in TKA and should be used selectively under optimum conditions.

PMID- 29221842
TI  - Comparison of an Uncemented Tapered Stem Design in Cobalt-Chrome vs Titanium at
      15-Year Follow-Up.
AB  - BACKGROUND: Cobalt-chromium (Co-Cr) and titanium (Ti) have been the most popular
      materials employed for cementless implants. The purpose of this study was to
      compare clinical and radiological results of a single stem design with both
      alloys at long-term follow-up. METHODS: Two hundred consecutive uncemented stems
      implanted in 171 patients (100 Co-Cr and 100 Ti implants) between 1999 and 2002
      were studied. Mean age of the patients was 60.9 years (range, 20-84). Clinical
      results were evaluated using the Harris hip score. The presence of thigh pain was
      also analyzed. Stem fixation was graded according to Engh criteria. Radiolucent
      lines, osteolysis, and stem subsidence were also analyzed. RESULTS: At 15-year
      follow-up, no stems had been revised. Both groups showed similar clinical results
      with mean Harris hip score of 93.4 (Co-Cr) vs 93.9 (Ti). There was no difference
      in the rate of thigh pain (11 vs 8.3, respectively, P = .507). Radiolucent lines
      were more frequent in the Co-Cr group (63.6% vs 35.6%, P < .001). CONCLUSION: Ti
      stems showed better osteointegration than Co-Cr stems, with a significantly lower
      incidence of radiolucent lines. However, this did not affect the clinical results
      or the appearance of thigh pain.

PMID- 29221843
TI  - A Comparison of the Accuracy of Clinician Prediction of Survival Versus the
      Palliative Prognostic Index.
AB  - CONTEXT: Survival predictions for advanced cancer patients impact many aspects of
      care, but the accuracy of clinician prediction of survival (CPS) is low.
      Prognostic tools such as the Palliative Prognostic Index (PPI) have been proposed
      to improve accuracy of predictions. However, it is not known if PPI is better
      than CPS at discriminating survival. OBJECTIVE: We compared the prognostic
      accuracy of CPS to PPI in patients with advanced cancer. METHODS: This was a
      prospective study in which palliative care physicians at our tertiary care cancer
      center documented both the PPI and CPS in hospitalized patients with advanced
      cancer. We compared the discrimination of CPS and PPI using concordance
      statistics, area under the receiver-operating characteristics curve (AUC), net
      reclassification index, and integrated discrimination improvement for 30-day
      survival and 100-day survival. RESULTS: Two hundred fifteen patients were
      enrolled with a median survival of 109 days and a median follow-up of 239 days.
      The AUC for 30-day survival was 0.76 (95% CI 0.66-0.85) for PPI and 0.58 (95% CI
      0.47-0.68) for CPS (P < 0.0001). Using the net reclassification index, 67% of
      patients were correctly reclassified using PPI instead of CPS for 30-day survival
      (P = 0.0005). CPS and PPI had similar accuracy for 100-day survival (AUC 0.62 vs.
      0.64; P = 0.58). CONCLUSION: We found that PPI was more accurate than CPS when
      used to discriminate survival at 30 days, but not at 100 days. This study
      highlights the reason and timing for using PPI to facilitate survival
      predictions.

PMID- 29221844
TI  - Gabapentin as an Adjuvant Therapy for Prevention of Acute Phantom-Limb Pain in
      Pediatric Patients Undergoing Amputation for Malignant Bone Tumors: A Prospective
      Double-Blind Randomized Controlled Trial.
AB  - CONTEXT: Gabapentin is reported to have an analgesic effect of reducing phantom
      limb pain (PLP) in adult patients. There is no study on preoperative use of
      gabapentin in pediatric population in terms of PLP prevention. OBJECTIVE: To
      determine whether gabapentin could be used as an adjuvant agent of opioid-based
      pain control to lower the rate of PLP in pediatric patients undergoing amputation
      for malignant bone tumors in observation period of 60 days postoperatively.
      METHODS: Pediatric patients who were diagnosed with osteosarcoma or Ewing's
      sarcoma around the knee and underwent amputation from May 2013 to March 2016 were
      registered to this prospective double-blind randomized controlled trial. Four
      days before amputation, the patients were randomized to a study group receiving
      oral gabapentin, and a control group receiving oral placebo, both for 30 days.
      Pain intensity was recorded using the visual analog scale at different time
      points in all patients. PLP was assessed daily during their postoperative
      hospital stay and at the last follow-up visit 60 days after operation. RESULTS:
      Of the 45 patients included in our study, 23 patients were randomized to
      gabapentin group and 22 to placebo group. There was no significant difference in
      preoperative baseline pain intensity between the two groups (P = 0.12). The
      overall postoperative pain intensity in gabapentin group was significantly lower
      than that in placebo group (P < 0.05). The rate of PLP in gabapentin group was
      significantly lower than that in placebo group (43.48% vs. 77.27%, P = 0.033) at
      the last follow-up visit. CONCLUSIONS: In pediatric patients, gabapentin shows
      the effect of preventing PLP and reducing postoperative pain intensity in acute
      period after amputation. Initiation of gabapentin therapy as an adjuvant to
      opioids before amputation is beneficial with no severe adverse effect.

PMID- 29221845
TI  - Characterizing the Role of U.S. Surgeons in the Provision of Palliative Care: A
      Systematic Review and Mixed-Methods Meta-Synthesis.
AB  - CONTEXT: The provision of palliative care varies appropriately by clinical
      factors such as patient age and severity of disease and also varies by provider
      practice and specialty. Surgical patients are persistently less likely to receive
      palliative care than their medical counterparts for reasons that are not clear.
      OBJECTIVES: We sought to characterize surgeon-specific determinants of palliative
      care in seriously ill and dying patients. METHODS: We performed a systematic
      review of the literature focused on surgery and palliative care within PubMed,
      CINAHL, EMBASE, Scopus, and Ovid Medline databases from January 1, 2000 through
      December 31, 2016 according to Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines. Quantitative and qualitative studies with primary
      data evaluating surgeons' attitudes, knowledge, and behaviors or experiences in
      care for seriously ill and dying patients were selected for full review by at
      least two study team members based on predefined inclusion criteria. Data were
      extracted based on a predetermined instrument and compared across studies using
      thematic analysis in a meta-synthesis of qualitative and quantitative findings.
      RESULTS: A total of 2589 abstracts were identified and screened, and 35 articles
      (26 quantitative and nine qualitative) fulfilled criteria for full review. Among
      these, 17 articles explored practice and attitudes of surgeons regarding
      palliative and end-of-life care, 11 articles assessed training in palliative
      care, five characterized surgical decision making, one described behaviors of
      surgeons caring for seriously ill and dying patients, and one explicitly
      identified barriers to use of palliative care. Four major themes across studies
      affected receipt of palliative care for surgical patients: 1) surgeons'
      experience and knowledge, 2) surgeons' attitudes, 3) surgeons' preferences and
      decision making for treatment, and 4) perceived barriers. CONCLUSIONS: Among the
      articles reviewed, surgeons overall demonstrated insight into the benefits of
      palliative care but reported limited knowledge and comfort as well as a multitude
      of challenges to introducing palliative care to their patients. These findings
      indicate a need for wider implementation of strategies that allow optimal
      integration of palliative care with surgical decision making.

PMID- 29221846
TI  - Prevailing Ethical Dilemmas Encountered by Physicians in Terminal Cancer Care
      Changed After the Enactment of the Natural Death Act: 15 Years' Follow-up Survey.
AB  - CONTEXT: Advance directive laws have influences on ethical dilemmas encountered
      by physicians caring for terminal cancer patients. OBJECTIVES: To identify the
      prevailing ethical dilemmas among terminal care physicians 15 years after the
      Natural Death Act was enacted in Taiwan. METHODS: This study is a cross-sectional
      survey from April 2014 to February 2015 using the clustering sampling method and
      a well-structured questionnaire. Targeted participants included physicians at
      oncology and related wards or palliative care units where terminal cancer care
      may be provided in Taiwan. RESULTS: Among the 500 physicians surveyed, 383
      responded (response rate 76.6%) and 346 valid questionnaires were included in the
      final analysis (effective response rate 69.2%). The most frequently identified
      ethical dilemma was "place of care," followed by "use of antimicrobial agents"
      and "artificial nutrition and hydration." The dilemma of "truth telling," which
      ranked first in the 2005-2006 survey, now ranked at the fourth place. Stepwise
      logistic regression analysis revealed that female gender and knowledge of
      palliative care were negatively correlated with the extent of dilemmas regarding
      issues of "life and death." CONCLUSION: The prevailing ethical dilemmas have
      changed in Taiwan 15 years after the enactment of the Natural Death Act,
      supporting that some previous strategies had worked. Our results suggest that
      education on the core values of palliative care, improvement of community-based
      hospice care program, and creating treatment guidelines with prognostication may
      resolve the current dilemmas. This type of survey should be adapted by individual
      countries to guide policy decisions on end-of-life care.

PMID- 29221847
TI  - Outpatient Pain Medication Use: An Electronic Daily Diary Study in Metastatic
      Breast Cancer.
AB  - CONTEXT: Understanding cancer patients' everyday pain experiences and their
      concomitant use of pain medication may help identify ways to improve pain
      management among outpatients. OBJECTIVES: This study examined the between-person
      and within-person associations between pain intensity and analgesic use in
      metastatic breast cancer patients. METHODS: Fifty-three women who were initiating
      treatment for metastatic breast cancer completed electronic diary assessments six
      times per day for 14 days. RESULTS: The likelihood of taking medication was found
      to depend on patients' average pain levels and on whether their pain was better
      or worse than usual at the time. Patients who typically experienced moderate-to
      high pain were more likely to be prescribed and to take analgesics than were
      patients who typically experienced low pain. However, these patients tended not
      to vary their medication use based on within-person fluctuations in pain. In
      contrast, patients who typically experienced low pain tended to increase their
      medication use at times when their pain was higher than usual but were less
      likely to use medication than were patients who typically experienced higher
      levels of pain. CONCLUSION: Our findings provide some evidence that patients with
      advanced cancer tend to use their pain medications appropriately. Patients with
      lower pain appear to be taking medications in response to increases in pain,
      whereas patients whose pain is typically more intense may be relying on other
      cues to prompt them to take analgesic medication. Clinicians may need to be
      sensitive to individual differences in the factors associated with pain
      medication use in daily life.

PMID- 29221849
TI  - Molecular Regulation of Fatty Acid Oxidation in Skeletal Muscle during Aerobic
      Exercise.
AB  - This review summarizes how fatty acid (FA) oxidation is regulated in skeletal
      muscle during exercise. From the available evidence it seems that acetyl-CoA
      availability in the mitochondrial matrix adjusts FA oxidation to exercise
      intensity and duration. This is executed at the step of mitochondrial fatty acyl
      import, as the extent of acetyl group sequestration by carnitine determines the
      availability of carnitine for the carnitine palmitoyltransferase 1 (CPT1)
      reaction. The rate of glycolysis seems therefore to be central to the amount of
      beta-oxidation-derived acetyl-CoA that is oxidized in the tricarboxylic acid
      (TCA) cycle. FA oxidation during exercise is also determined by FA availability
      to mitochondria, dependent on trans-sarcolemmal FA uptake via cluster of
      differentiation 36/SR-B2 (CD36) and FAs mobilized from myocellular lipid
      droplets.

PMID- 29221848
TI  - Menopausal-Related Symptoms in Women One Year After Breast Cancer Surgery.
AB  - CONTEXT: Approximately 60% to 100% of women with breast cancer experience at
      least one menopausal-related symptom. Little is known about associations between
      menopausal status and symptoms in women 12 months after breast cancer surgery.
      OBJECTIVES: The purpose of this study was to evaluate for differences in
      occurrence, severity, and distress of symptoms between pre- and postmenopausal
      women 12 months after breast cancer surgery. METHODS: Women with breast cancer (n
      = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence,
      severity, and distress of 46 common menopausal-related symptoms. Regression
      analyses were used to evaluate between-group differences in the seven symptoms
      that occurred in 30% and more of the sample (i.e., hot flashes, night sweats,
      depression, daytime sweats, joint pain or stiffness, wake during the night, and
      numbness or tingling). RESULTS: Of the 327 patients with breast cancer, who
      completed the 12-month assessment, 35.2% were premenopausal and 64.8% were
      postmenopausal before surgery. In the conditional models, when significant
      interactions were found, the differences in symptom occurrence rates between pre-
      and postmenopausal patients depended on their age. CONCLUSION: Regardless of
      menopausal status, women reported relatively high occurrence rates for several
      menopausal symptoms. Associations between symptom occurrence rates and menopausal
      status depended on the patient's age. During the development of a survivorship
      care plan, clinicians need to assess symptom burden within the context of a
      woman's menopausal status and salient demographic and clinical characteristics.
      This approach will assist with the prescription of more effective interventions.

PMID- 29221850
TI  - Isolation and molecular characterization of Leishmania infantum in urine from
      patients with visceral leishmaniasis in Brazil.
AB  - Leishmania infantum is a protozoan that causes visceral leishmaniasis, a
      potentially deadly neglected tropical disease. The gold standard for diagnosis
      has traditionally been detection of amastigotes in bone marrow or spleen
      aspirates, but this is an invasive procedure that carries the risk of serious
      complications. Newer PCR techniques are opening new avenues and tissues for
      testing. Therefore, we tested if amastigotes and DNA from L. infantum could be
      detected in patient urine. We detected L. infantum DNA in six out of 30 urine
      samples from patients with visceral leishmaniasis and the promastigotes were
      isolated in culture from the urine of one patient. These results suggest the
      feasibility of using urine samples to diagnose visceral leishmaniasis, especially
      in acute cases or renal infection, providing a valuable tool for doctors and
      clinicians to use for screening and diagnosis of leishmaniasis in patients.

PMID- 29221851
TI  - CCR5 chemokine receptor gene polymorphisms in ocular toxoplasmosis.
AB  - CC chemokine receptor type 5 (CCR5) is a chemokine receptor that influences the
      immune response to infectious and parasitic diseases. This study aimed to
      determine whether the CCR5Delta32 and CCR5 59029 A/G polymorphisms are associated
      with the development of ocular toxoplasmosis in humans. Patients with positive
      serology for Toxoplasma gondii were analyzed and grouped as 'with ocular
      toxoplasmosis' (G1: n=160) or 'without ocular toxoplasmosis' (G2: n=160). A
      control group (G3) consisted of 160 individuals with negative serology. The
      characterization of the CCR5Delta32 and CCR5 59029 A/G polymorphisms was by PCR
      and by PCR-RFLP, respectively. The difference between the groups with respect to
      the mean age (G1: mean age: 47.3, SD+/-19.3, median: 46 [range: 18-95]; G2: mean
      age: 61.3, SD+/-13.7, median: 61 [range: 21-87]; G3: mean age: 38.8, SD+/-17.9,
      median: 34 [range: 18-80]) was statistically significant (G1 vs.G2: p-value
      <0.0001; t=7.21; DF=318; G1 vs.G3: p-value <0.0001; t=4.32; DF=318; G2 vs. G3: p
      value <0.0001; t=9.62; DF=318). The Nagelkerke r2 value was 0.040. There were
      statistically significant differences for the CCR5/CCR5 (p-value=0.008;
      OR=0.261), AA (p-value=0.007; OR=2.974) and AG genotypes (p-value=0.018;
      OR=2.447) between G1 and G2. Individuals with the CCR5/CCR5 genotype and
      simultaneously the CCR5-59029 AA or AG genotypes have a greater risk of
      developing ocular toxoplasmosis (4% greater), which may be associated with a
      strong and persistent inflammatory response in ocular tissue.

PMID- 29221852
TI  - Captive-bred neotropical birds diagnosed with Cryptosporidium Avian genotype III.
AB  - Currently, there are only three valid species of Cryptosporidium infecting avian
      hosts, namely, Cryptosporidium meleagridis, Cryptosporidium baileyi,
      Cryptosporidium galli and Cryptosporidium avium in addition to 12 genotypes of
      unknown species status. The objectives of this study were to microscopically
      diagnose the presence of Cryptosporidium in birds from a commercial aviary
      located in Rio de Janeiro, Brazil; genotypically characterize species and/or
      genotypes of genus Cryptosporidum; and conduct sequencing and phylogenetic
      analyses to compare the obtained DNA sequences with those deposited in GenBank. A
      total of 85 fecal samples were collected from wild captive-bred birds: 48 of
      family Psittacidae and 37 of family Ramphastidae. Initially, a search for the
      presence of Cryptosporidium sp. oocysts was conducted using the centrifugal
      flotation in saturated sugar solution technique, after that, the collected
      samples were analyzed microscopically. Cryptosporidium infections were only
      detected in 24.32% of samples belonging to the family Ramphastidae. DNA was
      extracted from positive samples and molecular diagnostics was applied targeting
      the 18S rRNA gene, followed by sequencing and phylogenetic analysis. The
      Cryptosporidium Avian genotype III was diagnosed in this study more closely
      related to the gastric species. This is the first record of Cryptosporidium Avian
      genotype III in order Piciformes and family Ramphastidae, where three host
      species (Ramphastus toco, Ramphastus tucanus, and Pteroglossus bailloni) were
      positive for the etiologic agent. Based on the molecular data obtained, these
      wild birds raised in captivity do not represent a source of human
      cryptosporidiosis, considering that Cryptosporidium Avian genotype III does not
      constitute a zoonosis.

PMID- 29221853
TI  - Venous thromboembolism events after breast reconstructions with DIEP free flaps
      in 192 consecutive case.
AB  - BACKGROUND: Patient candidates for breast reconstruction with free deep inferior
      epigastric perforator flap (DIEP) may present several risk factors for venous
      thromboembolism (VTE). Risk identification is essential for appropriate VTE
      prophylaxis measures to be put in place. This study aims to investigate VTE
      incidence after DIEP flap breast reconstruction and to assess the accuracy of the
      Caprini Risk Assessment Model (RAM), which is the unique score validated to
      assess the VTE risk for plastic surgery procedures and identify patients at high
      VTE risk. METHODS: A chart review was conducted of 192 consecutive patients who
      underwent breast reconstruction with a DIEP flap from 1999 to 2016. VTE rate was
      assessed and the Caprini score was calculated for each patient and correlated
      with the VTE incidence. RESULTS: During the 90 post-operative days, four patients
      presented a pulmonary embolism (2.1%) and two patients (1%) had deep venous
      thrombosis (overall VTE incidence of 3.1%). Most patients (92.2%) were assessed
      as high-risk (Caprini score >5) and all VTE occurred among this group. Apart from
      the Caprini score, no specific single risk factor could be identified for VTE.
      CONCLUSIONS: Our data confirm that the Caprini RAM is a valuable assessment tool
      for VTE risk measurement among all patients undergoing autologous breast
      reconstruction. As most candidates for DIEP flap belong to the high-risk group,
      combined anticoagulation prophylaxis methods are required for most cases,
      particularly chemoprophylaxis up to four weeks postoperatively.

PMID- 29221854
TI  - From non-adaptive depression to general distress.

PMID- 29221855
TI  - Toll-like receptor-4 regulates anxiety-like behavior and DARPP-32
      phosphorylation.
AB  - Toll-like receptors (TLRs) play a crucial role in early innate immune responses
      to inflammatory agents and pathogens. In the brain, some members of the TLR
      family are expressed in glial cells and neurons. In particular, TLR4 has been
      involved in learning and memory processes, stress-induced adaptations, and
      pathogenesis of neurodegenerative disorders. However, the role of TLR4 in
      emotional behaviors and their underlying mechanisms are poorly understood. In
      this study, we investigated the role of TLR4 in emotional and social behavior by
      using different behavioral approaches, and assessed potential molecular
      alterations in important brain areas involved in emotional responses. TLR4
      knockout (KO) mice displayed increased anxiety-like behavior and reduced social
      interaction compared to wild type control mice. This behavioral phenotype was
      associated with an altered expression of genes known to be involved in emotional
      behavior [e.g., brain-derived neurotrophic factor (BDNF) and metabotropic
      glutamate receptors (mGluRs)]. Interestingly, the mRNA expression of dopamine-
      and cAMP-regulated phosphoprotein-32 (DARPP-32) was strongly upregulated in
      emotion-related regions of the brain in TLR4 KO mice. In addition, the
      phosphorylation levels at Thr75 and Ser97 in DARPP-32 were increased in the
      frontal cortex of TLR4 KO male mice. These findings indicate that TLR4 signaling
      is involved in emotional regulation through modulation of DARPP-32, which is a
      signaling hub that plays a critical role in the integration of numerous
      neurotransmitter systems, including dopamine and glutamate.

PMID- 29221857
TI  - Review of Simulation Training in Interventional Radiology.
AB  - Simulation training has evolved and is now able to offer numerous training
      opportunities to supplement the practice of and overcome some of the shortcomings
      of the traditional Master-Apprentice model currently used in medical training.
      Simulation training provides new opportunities to practice skills used in
      clinical procedures, crisis management scenarios, and everyday clinical practice
      in a risk-free environment. Procedural and nonprocedural skills used in
      interventional radiology can be taught with the use of simulation devices and
      technologies. This review will inform the reader of which clinical skills can be
      trained with simulation, the types of commercially available simulators and their
      educational validity, and the assessment tools used to evaluate simulation
      training.

PMID- 29221856
TI  - Light-triggered dissociation of self-assembled beta-amyloid aggregates into
      small, nontoxic fragments by ruthenium (II) complex.
AB  - : The self-assembly of beta-amyloid (Abeta) peptides into highly stable plaques
      is a major hallmark of Alzheimer's disease. Here, we report visible light-driven
      dissociation of beta-sheet-rich Abeta aggregates into small, nontoxic fragments
      using ruthenium (II) complex {[Ru(bpy)3]2+} that functions as a highly sensitive,
      biocompatible, photoresponsive anti-Abeta agent. According to our multiple
      analyses using thioflavin T, bicinchoninic acid, dynamic light scattering, atomic
      force microscopy, circular dichroism, and Fourier transform infrared
      spectroscopy, [Ru(bpy)3]2+ successfully disassembled Abeta aggregates by
      destabilizing the beta-sheet secondary structure under illumination of white
      light-emitting diode light. We validated that photoexcited [Ru(bpy)3]2+ causes
      oxidative damages of Abeta peptides, resulting in the dissociation of Abeta
      aggregates. The efficacy of [Ru(bpy)3]2+ is attributed to reactive oxygen
      species, such as singlet oxygen, generated from [Ru(bpy)3]2+ that absorbed photon
      energy in the visible range. Furthermore, photoexcited [Ru(bpy)3]2+ strongly
      inhibited the self-assembly of Abeta monomers even at concentrations as low as 1
      nM and reduced the cytotoxicity of Abeta aggregates. STATEMENT OF SIGNIFICANCE:
      Alzheimer's disease is the most common progressive neurodegenerative disease,
      affecting more than 13% of the population over age 65. Over the last decades,
      researchers have focused on understanding the mechanism of amyloid formation, the
      hallmark of various amyloid diseases including Alzheimer's and Parkinson's. In
      this paper, we successfully demonstrate the dissociation of beta-Amyloid (Abeta)
      aggregates into small, less-amyloidic fragments by photoexcited [Ru(bpy)3]2+
      through destabilization of beta-sheet secondary structure. We validated the light
      triggered dissociation of amyloid structure using multiple analytical tools.
      Furthermore, we confirmed that photoexcited [Ru(bpy)3]2+ reduces cytotoxicity of
      Abeta aggregates. Our work should open a new horizon in the study of Alzheimer's
      amyloid aggregation by showing the potential of photoexcited dye molecules as an
      alternative therapeutic strategy for treating Alzheimer's disease in future.

PMID- 29221858
TI  - Photochemical internalization enhanced macrophage delivered chemotherapy.
AB  - BACKGROUND: Macrophage (Ma) vectorization of chemotherapeutic drugs has the
      advantage for cancer therapy in that it can actively target and maintain an
      elevated concentration of drugs at the tumor site, preventing their spread into
      healthy tissue. A potential drawback is the inability to deliver a sufficient
      number of drug-loaded Ma into the tumor, thus limiting the amount of active drug
      delivered. This study examined the ability of photochemical internalization (PCI)
      to enhance the efficacy of released drug by Ma transport. METHODS: Tumor
      spheroids consisting of either F98 rat glioma cells or F98 cells combined with a
      subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used
      as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and
      laser irradiation at 670 nm. RESULTS: RAW264.7 Ma pulsed with DOX released the
      majority of the incorporated DOX within two hours of incubation. PCI
      significantly increased the toxicity of DOX either as pure drug or derived from
      monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids
      was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11%
      of the total initial hybrid spheroid cell number. CONCLUSION: Results show that
      RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI
      significantly increased the ability of both free and Ma-released DOX to inhibit
      the growth of tumor spheroids in vitro. The growth of F98 + DOX loaded Ma hybrid
      spheroids were synergistically reduced by PCI, compared to either photodynamic
      therapy or released DOX acting alone.

PMID- 29221859
TI  - Photodynamic Antimicrobial Chemotherapy (PACT), using Toluidine blue O inhibits
      the viability of biofilm produced by Candida albicans at different stages of
      development.
AB  - BACKGROUND: Candida albicans is an opportunistic fungus producing both
      superficial and systemic infections, especially in immunocompromised individuals.
      It has been demonstrated that C. albicans ability to form biofilms is a crucial
      process for colonization and virulence. Furthermore, a correlation between the
      development of drug resistance and biofilm maturation at Candida biofilms has
      been shown. Photodynamic Antimicrobial Chemotherapy (PACT) is a potential
      antimicrobial therapy that combines visible light and a non-toxic dye, known as a
      photosensitizer, producing reactive oxygen species (ROS) that can kill the
      treated cells. The objective of this study was to investigate the effects of
      PACT, using Toluidine Blue O (TBO) on the viability of biofilms produced by C.
      albicans at different stages of development. METHODS: In this study, the effects
      of PACT on both biofilm formation and viability of the biofilm produced by C.
      albicans were studied. Biofilm formation and viability were determined by a
      metabolic assay based on the reduction of XTT assay. In addition, the morphology
      of the biofilm was observed using light microscopy. RESULTS: PACT inhibited both
      biofilm formation and viability of the biofilm produced by C. albicans.
      Furthermore, PACT was able to decrease the number of both cells and filamentous
      form present in the biofilm structure. This inhibitory effect was observed in
      both early and mature biofilms. CONCLUSIONS: The results obtained in this study
      demonstrated the potential of PACT (using TBO) as an effective antifungal
      therapy, including against infections associated with biofilms at different
      stages of development.

PMID- 29221860
TI  - The Cellulose Synthases Are Cargo of the TPLATE Adaptor Complex.

PMID- 29221861
TI  - Prosthetic valve endocarditis in patients on hemodialysis.

PMID- 29221862
TI  - Physical activity, sedentary time, TV viewing, physical fitness and
      cardiovascular disease risk in adolescents: The HELENA study.
AB  - BACKGROUND: To examine the independent associations between physical activity
      (PA) intensities, sedentary time (ST), TV viewing, cardiorespiratory fitness
      (CRF) and muscular fitness (MF) with cardiovascular disease (CVD) risk in youth.
      METHODS: A cross-sectional study on 534 European adolescents (252 males, 282
      females, 12.5-17.5years). Minutes per day of light (LPA), moderate (MPA) and
      vigorous (VPA) PA and total ST were measured using accelerometers. TV viewing
      time was measured using a questionnaire. CRF and MF were measured using the 20m
      shuttle run test and a hand dynamometer respectively. CVD outcomes included
      markers of body composition (body mass index (BMI), waist circumference (WC),
      WC/height (Ht) and sum of skinfolds (SumSF)), blood pressure, blood lipids and
      insulin resistance (HOMA-IR). Clustered CVD risk was calculated using SumSF, HOMA
      IR, blood lipids and blood pressure. RESULTS: LPA had a significant positive
      independent relationship with all body composition outcomes (P<0.001) and
      clustered CVD risk (P=0.046). VPA was negatively related to SumSF (P<0.001), BMI
      (P=0.018), WC/Ht (P=0.013) and clustered CVD risk (P=0.001), but was non
      significant for all when other exposures were considered (P>0.10). MPA had a
      negative independent relationship with only WC (P=0.029) and ST was not
      significantly related to CVD risk (P>0.16). TV viewing had a significant positive
      independent relationship with HOMA-IR (P<0.001) and clustered CVD risk (P=0.019).
      CRF (all P<0.002) and MF (all P<0.009) had a negative independent relationship
      with body composition outcomes and clustered CVD risk. CONCLUSIONS: Public health
      guidelines should prioritize on increasing levels of CRF, MF and VPA, and
      reducing TV viewing time to lower CVD risk in youth.

PMID- 29221864
TI  - No 356-Congelation d'ovules pour pallier le declin de la fertilite lie a l'age.

PMID- 29221863
TI  - [Cutaneous pigmentation related to intravenous iron extravasation: Analysis from
      the French pharmacovigilance database].
AB  - INTRODUCTION: Intravenous iron infusion may be complicated by extravasation and
      lead to cutaneous pigmentation. METHODS: We queried the French pharmacovigilance
      database to assess the spontaneously reported cases over the 2000-2016 period.
      RESULTS: Fifty-one cases of cutaneous pigmentation related to intravenous iron
      extravasation were retrieved, none was associated to necrosis. Most of patients
      were women aged 20 to 49 years old. The pigmentation was mostly a brown
      coloration, persisting over one month in 19 cases (37.2%) and over 6 months in 9
      cases (17.6%). The management of extravasation and pigmentation was heterogeneous
      and was rarely followed by a decrease of the coloration. CONCLUSION: Cutaneous
      pigmentation after intravenous iron extravasation can persist over time and
      create an aesthetic prejudice, particularly in young women. Standardized
      extravasation and iron-induced pigmentation management procedures appear
      necessary.

PMID- 29221865
TI  - Methodologies to determine b-term coefficients revisited.
AB  - The accuracy of the longitudinal diffusion term (b-term) plays a vital role in
      the study of mass transfer mechanisms in high performance liquid chromatography
      (HPLC). In this study, three commonly used methodologies (peak parking; fitting
      of an experimental van Deemter curve; and the so-called dynamic method) for the
      determination of the b-term constant were investigated in detail. The three
      methods were compared based on their mutual agreement, the intra- and inter-day
      variation of the obtained values and the time required to measure them. Whereas
      the dynamic method was found to be plagued by impractically long waiting times
      and concomitant baseline variations compromising accurate measurements of the
      band broadening, the two other methods lead to very similar b-values, i.e., well
      within the 1% RSD inter-day variation typically marking both methods in the
      present study. The best way to study the agreement of the peak parking and plate
      height fitting method is in a plot of h.nu versus nu, providing a much better
      zoom on the b-term region of the van Deemter curve than the customarily employed
      h versus nu-curve and hence allowing to identify any anomalous measurement values
      (usually related to measurements with a long experimentation time). Verifying the
      mutual agreement between both methods is proposed here as an additional accuracy
      check of the obtained data.

PMID- 29221866
TI  - A capillary zone electrophoresis method for detection of Apolipoprotein C-III
      glycoforms and other related artifactually modified species.
AB  - ApolipoproteinC-III (ApoC-III) is a human plasma glycoprotein whose O
      glycosylation can be altered as a result of congenital disorders of glycosylation
      (CDG). ApoC-III exhibits three major glycoforms whose relative quantification is
      of utmost importance for the diagnosis of CDG patients. Considering the very
      close structures of these glycoforms and their tendency to adsorb on the
      capillary, a thorough optimization of capillary electrophoresis (CE) parameters
      including preconditioning and in-between rinsing procedures was required to
      efficiently separate all the ApoC-III glycoforms. Permanent coatings did not
      contribute to high resolution separations. A fast and reliable method based on a
      bare-silica capillary combining the effect of urea and diamine additives allowed
      to separate up to six different ApoC-III forms. We demonstrated by a combination
      of MALDI-TOF mass spectrometry (MS) analyses and CE of intact and neuraminidase
      treated samples that this method well resolved glycoforms differing not only by
      their sialylation degree but also by carbamylation state, an undesired chemical
      modification of primary amines. This method allowed to demonstrate the
      carbamylation of ApoC-III glycoforms for the first time. Our CZE method proved
      robust and accurate with excellent intermediate precision regarding migration
      times (RSDs < 0.7%) while RSDs for peak areas were less than 5%. Finally, the
      quality of three distinct batches of commercial ApoC-III obtained from different
      suppliers was assessed and compared. Quite similar but highly structurally
      heterogeneous ApoC-III profiles were observed for these samples.

PMID- 29221867
TI  - Modelling ordered packed beds of spheres: The importance of bed orientation and
      the influence of tortuosity on dispersion.
AB  - Ordered packing has previously been considered for porous media applications in
      the industrial and analytical worlds, with implementation constrained only by the
      lack of feasible fabrication methods. Additive manufacturing now provides the
      answer to this limitation, which leads to the novel domain of customized ordered
      packing and a variety of optimized geometries. In this work, the chromatographic
      behaviour of ordered configurations of particles was described using
      computational fluid dynamics methods based on the Lattice Boltzmann Model. The
      model was first validated by matching van Deemter trends for ordered and random
      packings shown in previous research. The influence of rotations of the ordered
      configurations was then considered, indicating that orientational changes with
      respect to the main flow axis can strongly affect minimum plate height. In
      particular, it is demonstrated that targeted rotations of ordered packings can
      reduce axial dispersion while improving transverse dispersion, thus improving
      chromatographic performance. This principle is clearly shown in a strong linear
      correlation between tortuosity and plate height, offering an additional parameter
      to enable a priori control of the performance of ordered packings. Furthermore,
      rotation of the packing does not change porosity or surface area and has a
      relatively small effect on permeability. Thus, highly permeable packings with
      poor dispersion can be improved in terms of chromatographic impedance by simple
      rotation of the packing orientation. This work further demonstrates the
      advantages of ordered packings over randomly packed beds, and introduces new
      perspectives on the development of chromatographic structures with improved
      performance.

PMID- 29221868
TI  - Influence of hydrogen bond accepting ability of anions on the adsorption
      performance of ionic liquid surface molecularly imprinted polymers.
AB  - To illuminate the influence mechanism of anionic structure of ionic liquids (ILs)
      on the adsorption performance of surface molecularly imprinted polymers (MIPs),
      in this work, six newly designed MIPs were prepared on the surface of amino
      poly(styrene-divinylbenzene) particles by using imidazolium ILs with the same
      cation [C4mim]+ but different anions (Cl, CH3SO3, PF6, BF4, C4F7O2, C4F9SO3) as
      template molecules, methacrylic acid as functional monomer, and ethylene
      dimethacrylate as cross-linker. The resulting MIP materials were characterized by
      IR and SEM, and the influence of hydrogen bond accepting ability of anions on the
      adsorption performance of the MIPs for the ILs was investigated in acetonitrile.
      It was found that adsorption capacity of the MIPs towards the ILs decreased in
      the order MIP[C4mim][Cl] > MIP[C4mim][C4F7O2] >= MIP[C4mim][BF4] and
      MIP[C4mim][CH3SO3] > MIP[C4mim][C4F9SO3] > MIP[C4mim][PF6], which is in good
      agreement with the ability of anions of the ILs to form hydrogen bonds.
      Ultraviolet, 1H-NMR and 35Cl-NMR spectroscopy was then used to study the
      interactions of anions of the ILs with the functional monomer. It was found that
      the hydrogen bond interaction between anions of the ILs and acidic proton of the
      functional monomer was the main driving force for the high adsorption selectivity
      of the imprinted polymers, and the stronger hydrogen bond interaction indicates
      higher binding capacity and higher selectivity of the polymers towards the ILs.
      It was also verified that the ILs with stronger hydrogen bond accepting ability
      of anions could be selectively extracted by the corresponding IL-MIPs. These
      results may provide new insight into the recognition mechanism of MIPs for ILs,
      and are also useful for the rational design of this new class of imprinting
      materials.

PMID- 29221869
TI  - Characteristics of hospitalizations due to acute stroke in the Silesian Province,
      Poland, between 2009 and 2015.
AB  - INTRODUCTION: The available data on acute stroke (AS) in Poland come mainly from
      non-representative cohorts or are outdated. Therefore, the current study was done
      to access the most recent data on AS in the industrial region that covers 12%
      (4.6mln) of the country's population. OBJECTIVE: To evaluate the epidemiological
      data of AS in the Silesian Province, Poland. PATIENTS AND METHODS: Analysis of
      the data from stroke questionnaires, obligatory for all patients hospitalized due
      to AS and administered by the only public health insurer in Poland (the National
      Health Fund) between 2009 and 2015 (n=81,193). RESULTS: The annual number of
      hospitalizations due to AS in the analyzed period was between 239 and 259 per
      100,000 inhabitants of the Silesian Province. Haemorrhagic stroke constituted
      13.3%, ischaemic stroke - 85.5%, and unspecified stroke - 1.2%. The average age
      of patients was 71.6+/-12.2 years (M 68.2+/-11.9, F 74.8+/-11.9, P<0.05). The
      mean duration of hospitalization was 17+/-16 days for haemorrhagic stroke, and
      14+/-11 days for ischaemic stroke. Large-artery atherosclerosis (36.1%) and
      cardioembolism (18.7%) constituted the main causes of ischaemic stroke. Overall
      hospital mortality for AS was 18% (haemorrhagic - 40.8%, ischaemic - 14.9%). A
      decreasing trend in mortality was observed in ischaemic but not in haemorrhagic
      stroke. In-hospital mortality was significantly higher in women than in men
      (P<0.05). CONCLUSIONS: This comprehensive long-term analysis of the
      epidemiological situation related to AS in the industrial region of Poland should
      encourage further development of educational and treatment programmes for
      improvement in the health status of the population.

PMID- 29221870
TI  - Estimation of CO2 emissions from waste incinerators: Comparison of three methods.
AB  - Climate-relevant CO2 emissions from waste incineration were compared using three
      methods: making use of CO2 concentration data, converting O2 concentration and
      waste characteristic data, and using a mass balance method following
      Intergovernmental Panel on Climate Change (IPCC) guidelines. For the first two
      methods, CO2 and O2 concentrations were measured continuously from 24 to 86 days.
      The O2 conversion method in comparison to the direct CO2 measurement method had a
      4.8% mean difference in daily CO2 emissions for four incinerators where analyzed
      waste composition data were available. However, the IPCC method had a higher
      difference of 13% relative to the direct CO2 measurement method. For three
      incinerators using designed values for waste composition, the O2 conversion and
      IPCC methods in comparison to the direct CO2 measurement method had mean
      differences of 7.5% and 89%, respectively. Therefore, the use of O2 concentration
      data measured for monitoring air pollutant emissions is an effective method for
      estimating CO2 emissions resulting from waste incineration.

PMID- 29221871
TI  - Investigation on paper cup waste degradation by bacterial consortium and
      Eudrillus eugeinea through vermicomposting.
AB  - Disposable Paper cups are a threat to the environment and are composed of 90%
      high strength paper with 5% thin coating of polyethylene. This polyethylene
      prevents the paper cup from undergoing degradation in the soil. Hence, in the
      present study two different approaches towards the management of paper cup waste
      through vermicomposting technology has been presented. The experimental setup
      includes 2 plastic reactors namely Vermicompost (VC) (Cow dung + Paper cup waste
      + Earthworm (Eudrillus eugeinea)) and Vermicompost with bacterial consortium
      (VCB) (Cow dung + Paper cup waste + Eudrillus eugeinea + Microbial consortia such
      as Bacillus anthracis, B. endophyticus, B. funiculus, B. thuringiensis, B.
      cereus, B. toyonensis, Virigibacillius chiquenigi, Acinetobacter baumanni and
      Lactobacillus pantheries). After treatment the physicochemical parameters were
      analysed. The results showed that the values of TOC (26.52 and 37.47%), TOM
      (36.01 and 33.13%) and C/N (15.02 and 11.92%) ratio are reduced in both VC and
      VCB whereas, the values of pH (8.01 and 7.56), EC (1.2-1.9 us-1 and 1.4-1.9 us
      1), TP (46.1 and 51%), TMg (50.52 and 64.3%), TCa (50 and 64%), TNa (1.39 and
      1.75%) and TK (1.75 and 1.86%) have increased. This study substantiates the
      addition of the microbial consortia augmenting the degradation in VCB reactor by
      reducing the period of process from 19 to 12 weeks. Further the characterisation
      of the vermicompost prepared from paper cup with FT-IR shows high degradation of
      carboxylic and aliphatic group; SEM analysis shows the disaggregation of
      cellulose and lignin; XRD shows the degradation of cellulose. All these analyses
      endorse the degradation of the paper cup waste faster with microbes (VCB). Thus,
      this present study high lights management of the paper cup waste in a relatively
      short period of time.

PMID- 29221872
TI  - Proposal of concentration limits for determining the hazard property HP 14 for
      waste using ecotoxicological tests.
AB  - Different ecotoxicological test batteries and concentration limits have been
      proposed to assess the hazard property (HP) HP 14 'Ecotoxic' for waste in the
      European Union and its member states. In test batteries, if the concentration of
      waste in the culture/dilution medium producing 50% of inhibitory biological
      effect in one or more test(s) is below the concentration limit of the test, the
      waste is classified as hazardous. A summarized review of the test batteries
      proposed since 1998 is presented. The last proposed test battery uses seven
      aquatic and terrestrial species with standardized methods, but with options and
      uniform concentration limits of 10% of waste eluate or solid waste in the
      culture/dilution medium. No attempt was made to match this hazard assessment with
      the classification made in the European List of Waste (LoW). The aim of this
      paper is to propose for the same test battery (reduced to 6 tests without
      options) concentration limits that match with the European List of Waste. This
      list was taken as reference (despite the fact that waste can be hazardous for
      other properties than the most frequent HP 14, and its partly political nature
      for some opinions). The concentration limits (CLs) for tests are the
      concentrations producing the highest ecotoxicological effects for each test
      observed in a non-hazardous waste set. Data from Germany, France and Belgium
      (from in total 5 different sources from 2009 to 2016) with the above-mentioned
      test battery (without options) were gathered for 81 samples, being the largest
      set ever published. In total, ten non-hazardous (NH) waste samples (as defined by
      the LoW and for most of them checked by chemical composition) were used to
      establish CLs. These CLs were then applied to 13 hazardous (H) waste by the LoW,
      and all were classified as hazardous. The matching of the resulting
      classification with the LoW is convincing. For the 58 'mirror entries' in the LoW
      (hazardous or not depending of the presence of hazardous substances), 37 were
      classified H (64%) and 21 were classified NH (36%). These concentration limits
      can be refined with the method proposed here, as soon as additional data of NH
      waste (by list and by composition) are available. The test battery (without
      options) and the concentration limits (in percent of waste in the
      culture/dilution medium) proposed are the following: A waste is hazardous for HP
      14 'Ecotoxic' if the concentration of waste (eluate or solid) in the
      culture/dilution medium producing 50% of biological effect relative to the
      control EC50-30 min of Vibrio fischeri (EN ISO 11348-3) is lower than 15.8%, or
      if the EC50-72 h of Pseudokirchneriella subcapitata (EN ISO 8692) is lower than
      7.03%, or if the EC50-48 h of Daphnia magna (EN ISO 6341) is lower than 7.95%, or
      if the EC50-6h of Arthrobacter globiformis (ISO 18187) is lower than 2.25%, or if
      the EC50-14d of Brassica rapa (EN ISO 11269-2) is lower than 13.7%, or if the
      EC50-48 h of Eisenia fetida avoidance test (ISO 17512-1) is lower than 3.75%.
      These CLs range between 2% and 16%, which is in line with the typically 10%
      concentration proposed without validation. To fix regulatory concentration
      limits, the regulators can use these CLs and the uncertainty of the
      ecotoxicological tests (standard deviation of inter-laboratory reproducibility
      typically of 25% of the mean, as published in the standards). Classification of
      waste for HP 14 with these tests and concentration limits will agree with the
      European List of Waste.

PMID- 29221873
TI  - Modeling and prediction of regional municipal solid waste generation and
      diversion in Canada using machine learning approaches.
AB  - The main objective of this study was to develop models for accurate prediction of
      municipal solid waste (MSW) generation and diversion based on demographic and
      socio-economic variables, with planned application of generating Canada-wide MSW
      inventories. Models were generated by mapping residential MSW quantities with
      socio-economic and demographic parameters of 220 municipalities in the province
      of Ontario, Canada. Two machine learning algorithms, namely decision trees and
      neural networks, were applied to build the models. Socio-economic variables were
      derived from Canadian Census data at regional and municipal levels. A data pre
      processing and integration framework was developed in Matlab(r) computing
      software to generate datasets with sufficient data quantity and quality for
      modeling. Results showed that machine learning algorithms can be successfully
      used to generate waste models with good prediction performance. Neural network
      models had the best performance, describing 72% of variation in the data. The
      approach proposed in this study demonstrates the feasibility of creating tools
      that helps in regional waste planning by means of sourcing, pre-processing,
      integrating and modeling of publically available data from various sources.

PMID- 29221874
TI  - Re: Pentoxifylline: a review of its use in osteoradionecrosis.

PMID- 29221875
TI  - The application of the FRIDEX calibration of the FRAX tool to determine the
      absolute risk of osteoporotic fracture among Spanish women.

PMID- 29221876
TI  - Conventional Versus Hypofractionated Radiation Therapy for Localized Prostate
      Cancer: A Meta-analysis of Randomized Noninferiority Trials.
AB  - CONTEXT: Whether hypofractionated radiation therapy (RT) compared with
      conventionally fractionated RT provides comparable or possibly improved cancer
      control without increased toxicity in localized prostate cancer (PC) remains
      unknown. OBJECTIVE: Realizing from the CHHiP trial that outcomes are highly
      sensitive to the dose fractionation schedule and number of treatments, we
      conducted a systematic review and meta-analysis selecting only the randomized
      noninferiority trials, because the randomized arms closely approximated one
      another in terms of the dose fractionation schedule, and compared cancer control
      and toxicity of hypofractionated RT with conventionally fractionated RT for
      localized PC. EVIDENCE ACQUISITION: Randomized noninferiority trials evaluating
      hypofractionated (2.4-4Gy daily fractions for 15-30 treatments) versus
      conventionally fractionated RT (1.8-2Gy daily fractions for 40-45 treatments) in
      men with localized PC were selected. Studies that were not noninferiority trials,
      used extreme hypofractionation, or treated metastatic disease were excluded.
      Three studies were retained for analysis. Data were pooled using a random-effects
      model to determine hazard ratio (HR) and risk ratio (RR). Heterogeneity was
      assessed via chi-square test, I2 statistics, and metaregression. The primary
      outcome was disease-free survival (DFS), defined as death from any cause or
      biochemical, local, regional, or distant progression. EVIDENCE SYNTHESIS: Of the
      5484 men, 3553 (64.8%) had intermediate-risk PC. Hypofractionated RT as compared
      with conventionally fractionated RT was associated with significantly improved
      DFS (HR 0.869; 95% confidence interval [CI], 0.757, 0.998; p=0.047), whereas
      overall survival was not (HR 0.84; 95% CI, 0.66, 1.07; p=0.16). Acute grade 2 or
      higher gastrointestinal toxicity was significantly increased with
      hypofractionation (RR 1.42; 95% CI 1.15, 1.77; p=0.002); however, this did not
      translate into late grade 2 or higher gastrointestinal toxicity. An increase in
      late grade 2 or higher genitourinary complications was observed (RR 1.18; 95% CI
      0.98, 1.43; p=0.08). CONCLUSIONS: Hypofractionated RT as compared with
      conventionally fractionated RT could improve DFS in men with intermediate-risk PC
      and, therefore, would be reasonable to consider in men who do not have risk
      factors for late genitourinary complications. PATIENT SUMMARY: Treatment with a
      shorter course of radiation, using higher doses per treatment over fewer days,
      may be the preferred approach in appropriately selected patients with localized
      prostate cancer.

PMID- 29221877
TI  - Guide to research in academic global surgery: A statement of the Society of
      University Surgeons Global Academic Surgery Committee.
AB  - Global surgery is an emerging academic discipline that is developing in tandem
      with numerous policy and advocacy initiatives. In this regard, academic global
      surgery will be crucial for measuring the progress toward improving surgical care
      worldwide. However, as a nascent academic discipline, there must be rigorous
      standards for the quality of work that emerges from this field. In this white
      paper, which reflects the opinion of the Global Academic Surgery Committee of the
      Society for University Surgeons, we discuss the importance of research in global
      surgery, the methodologies that can be used in such research, and the challenges
      and benefits associated with carrying out this research. In each of these topics,
      we draw on existing examples from the literature to demonstrate our points. We
      conclude with a call for continued, high-quality research that will strengthen
      the discipline's academic standing and help us move toward improved access to and
      quality of surgical care worldwide.

PMID- 29221878
TI  - Universal insurance and an equal access healthcare system eliminate disparities
      for Black patients after traumatic injury.
AB  - BACKGROUND: Although inequities in trauma care are reported widely, some groups
      have theorized that universal health insurance would decrease disparities in care
      for disadvantaged minorities after a traumatic injury. We sought to examine the
      presence of racial disparities in outcomes and healthcare utilization at 30- and
      90-days after discharge in this universally insured, racially diverse, American
      population treated for traumatic injuries. METHODS: This work studied adult
      beneficiaries of TRICARE treated at both military and civilian trauma centers
      2006-2014. We included patients with an inpatient trauma encounter based on
      International Classification of Diseases, 9th revision (ICD-9) code. The
      mechanism and severity of injury, medical comorbidities, region and environment
      of care, and demographic factors were used as covariates. Race was considered the
      main predictor variable with Black patients compared to Whites. Logistic
      regression models were employed to assess for risk-adjusted differences in 30-
      and 90-day outcomes between Blacks and Whites. RESULTS: A total of 87,112
      patients met the inclusion criteria. Traditionally encountered disparities for
      Black patients after trauma, including increased rates of mortality, were absent.
      We found a statistically significant decrease in the odds of 90-day complications
      for Blacks (OR 0.91; 95% CI 0.84-0.98; P = 0.01). Blacks also had lesser odds of
      readmission at 30-days (OR 0.87; 95% CI 0.79-0.94; P = 0.002) and 90-days (OR
      0.86; 95% CI 0.79-0.93; P < 0.001). CONCLUSION: Our findings support the idea
      that in a universally insured, equal access system, historic disparities for
      racial and ethnic minorities, including increased postinjury morbidity, hospital
      readmission, and postdischarge healthcare utilization, are decreased or even
      eliminated.

PMID- 29221879
TI  - Surveillance of patients with intraductal papillary mucinous neoplasm with and
      without pancreatectomy with special reference to the incidence of concomitant
      pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: The presence of an intraductal papillary mucinous neoplasm is
      important in the detection of concomitant pancreatic ductal adenocarcinoma. The
      aim of this study was to elucidate the incidence and timing of development of
      concomitant pancreatic ductal adenocarcinoma in patients with and without
      pancreatectomy for intraductal papillary mucinous neoplasm. METHODS: We reviewed
      retrospectively the surveillance data for 22 patients who underwent
      pancreatectomy for pancreatic ductal adenocarcinoma concomitant with intraductal
      papillary mucinous neoplasm (pancreatic ductal adenocarcinoma-resection group),
      180 who underwent pancreatectomy for intraductal papillary mucinous neoplasm
      (intraductal papillary mucinous neoplasm-resection group), and 263 whose
      intraductal papillary mucinous neoplasms were left untreated (nonresection
      group). The incidence and timing of the development of a concomitant pancreatic
      ductal adenocarcinoma during the surveillance of patients with and without
      partial pancreatectomy for intraductal papillary mucinous neoplasm were
      investigated using the Kaplan-Meier method. RESULTS: During a median surveillance
      period of 40 months (range 6-262 months), 5 patients in the pancreatic ductal
      adenocarcinoma-resection group, 6 in the intraductal papillary mucinous neoplasm
      resection group, and 8 in the nonresection group developed concomitant pancreatic
      ductal adenocarcinoma. The estimated 5-year (17%) and 10-year (56%) cumulative
      incidences of secondary pancreatic ductal adenocarcinoma in the pancreatic ductal
      adenocarcinoma-resection group were significantly greater than those in the other
      two groups (P < .01). Conversely, the difference in the estimated cumulative
      incidence of concomitant pancreatic ductal adenocarcinoma between the intraductal
      papillary mucinous neoplasm-resection and nonresection groups was not significant
      (5-year, 5.0% vs 2.2%; 10-year, 5.0% vs 8.7%; P = .87). CONCLUSION: Long-term
      (>=5-year) surveillance in patients with intraductal papillary mucinous neoplasm
      is necessary and important because of the potential for development of
      concomitant pancreatic ductal adenocarcinoma. Those with a history of resection
      of concomitant pancreatic ductal adenocarcinoma at the time of the initial
      operation are at quite high risk for the development of secondary pancreatic
      ductal adenocarcinoma.

PMID- 29221880
TI  - Hemodialysis catheter colonized by Pandoraea spotorum.

PMID- 29221881
TI  - Hepatotoxicity associated with eculizumab in a patient with atypical hemolytic
      uremic syndrome.

PMID- 29221882
TI  - Effective inhibition of Cbf-14 against Cryptococcus neoformans infection in mice
      and its related anti-inflammatory activity.
AB  - Cbf-14 (RLLRKFFRKLKKSV), a designed peptide derived from cathelicidin family AMP,
      has proven to be potent against drug-resistant bacteria. In the present study, we
      investigated the anti-cryptococcal activity of Cbf-14 in vitro and in a pulmonary
      infection mouse model. Sensitivity test indicated that Cbf-14 possessed effective
      antifungal activity against Cryptococcus neoformans with an MIC of 4-16 ug/ml,
      and killing experiments showed that fungicidal activity was achieved after only 4
      h treatment with Cbf-14 at 4* MIC concentrations in vitro. Meanwhile, Cbf-14 was
      effective at prolonging the survival of infected mice when compared with
      controls, and significantly inhibited the secretion of pro-inflammatory cytokines
      TNF-alpha, IL-1beta and IL-6, suggesting its anti-inflammatory activity against
      fungal infections. As a positively charged peptide, Cbf-14 was proven to
      neutralize the negative zeta potential of the fungal cell surface, disrupt the
      capsule polysaccharide of fungi, and further damage cell membrane integrity.
      These results were confirmed by flow cytometry analysis of the fluorescence
      intensity after PI staining, while cell membrane damage could be clearly observed
      by transmission electron microscopy after Cbf-14 (4* MIC) treatment for 1 h. In
      addition, Cbf-14 increased the IL-10 levels in cultured RAW 264.7 cells, which
      were stimulated by C. neoformans infection. The obtained data demonstrated that
      Cbf-14 could rapidly kill C. neoformans cells in vitro, effectively inhibit C.
      neoformans induced-infection in mice, and inhibit inflammation in vitro / vivo.
      Therefore, Cbf-14 could potentially be used for the treatment of fungal
      infections clinically.

PMID- 29221883
TI  - Anti-neuroinflammatory effects of sesquiterpenoids isolated from Nardostachys
      jatamansi.
AB  - Two new nardosinone-type sesquiterpenoids, namely kanshone J (1) and kanshone K
      (2) along with seven known terpenoids (3-9) were isolated from the rhizomes and
      roots of Nardostachys jatamansi DC (Valerianaceae). The structures of these
      compounds were determined mainly by analysis of 1D-, 2D-NMR and MS data. In
      addition, the absolute configuration of compound 1 was assigned by application of
      the modified Mosher's method. In an initial assay to evaluate their anti
      neuroinflammatory effects, compounds 1-5 and 9 exhibited dose-dependent
      inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production in BV2 cells, with IC50 values ranging from 2.43 to 46.54 MUM.
      Particularly, desoxo-narchinol A (3) and narchinol B (4) significantly inhibited
      LPS-induced NO overproduction in BV2 cells with IC50 values of 3.48 +/- 0.47 and
      2.43 +/- 0.23 MUM, respectively. Furthermore, compounds 3 and 4 exhibited anti
      neuroinflammatory effects by inhibiting the production of pro-inflammatory
      mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase
      (iNOS), and cyclooxygenase-2 (COX-2) proteins, and pro-inflammatory cytokines,
      such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF)
      alpha, in LPS-stimulated BV2 and primary microglial cells.

PMID- 29221884
TI  - [Efficacy and tolerance of tocilizumab for corticosteroid sparing in giant cell
      arteritis and aortitis: Experience of Nimes University Hospital about eleven
      patients].
AB  - INTRODUCTION: Giant cell arteritis is a large-vessels vasculitis, which treatment
      consists in a slowly-tappered steroid-therapy. Immunosuppressive agents are
      sometimes used in case of steroid-dependance. We have conducted an observationnal
      retrospective study including patients treated with tocilizumab for a giant cell
      arteritis or an aortitis in the internal medicine department at the Nimes
      University Hospital. RESULTS: Eleven patients were included between 2011 and
      2016, who had been treated only with prednisone. Tocilizumab was used because of
      steroid-dependance for nine patients, delirium under steroids for one patient and
      unefficiency of steroids for an other patient. Infusions of tocilizumab,
      administred monthly at 8mg/kg, led to clinical and biological remission for all
      patients. Consequently, prednisone was tappered under 10mg/d for ten patients
      after six months of treatment with tocilizumab. Eight cases of non-severe
      infection were reported; also two cases of dyslipidemia, one case of prurit and
      one case of moderate neutropenia. Two relapses were observed after the end of
      treatment, in patients treated with less than twelve infusions. CONCLUSION:
      Tocilizumab could be efficient and well-tolerated in steroid-dependent giant cell
      arteritis and aortitis. The modalities of its use remain to be precised.

PMID- 29221885
TI  - [Design of a questionnaire on the knowledge and attitudes of the population of
      Madrid (Spain) facing the end-of-life].
AB  - OBJECTIVE: To create and validate a questionnaire about knowledge and attitudes
      of the general population in Madrid (Spain) about life's end stage. METHOD: A
      descriptive study designed as a structured self-administered questionnaire,
      validated by seven Madrid Health Service professional experts and assessed
      through a pilot study. RESULTS: The questionnaire consisted of 42 questions,
      divided into six modules: 1) decisions and psychological-physical care at life's
      end; 2) palliative care; 3) euthanasia and assisted suicide; 4) advance
      directives document; 5) spiritual factors; and 6) socio-demographic data.
      CONCLUSIONS: The questionnaire was a useful, indirect method to ascertain the
      opinion of life's end in the Autonomous Region of Madrid. If it were applied in
      primary health care and hospital care, comparisons could be made among users in
      different autonomous regions of Spain.

PMID- 29221886
TI  - A model including sarcopenia surpasses the MELD score in predicting waiting list
      mortality in cirrhotic liver transplant candidates: a competing risk analysis in
      a national cohort.
AB  - BACKGROUND & AIMS: Frail patients with low model for end-stage liver disease
      (MELD) scores may be under-prioritised. Low skeletal muscle mass, namely
      sarcopenia, has been identified as a risk factor for waiting list mortality. A
      recent study proposed incorporating sarcopenia in the MELD score (MELD-Sarcopenia
      score). We aimed to investigate the association between sarcopenia and waiting
      list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD + 10.35 *
      Sarcopenia). METHODS: We identified consecutive patients with cirrhosis listed
      for liver transplantation in the Eurotransplant registry between 2007-2014 and
      measured skeletal muscle mass on computed tomography. A competing risk analysis
      was used to compare survival of patients with and without sarcopenia, and
      concordance (c) indices were calculated to assess performance of the MELD and
      MELD-Sarcopenia score. We created a nomogram of the best predictive model.
      RESULTS: We included 585 patients with a median MELD score of 14 (interquartile
      range 9-19), of which 254 (43.4%) were identified as having sarcopenia. Median
      waiting list survival was shorter in patients with sarcopenia than those without
      (p <0.001). This effect was even more pronounced in patients with MELD <=15. The
      discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for three
      month mortality was lower than MELD score alone (c-index 0.839). Apart from
      sarcopenia and MELD score, other predictive variables were occurrence of hepatic
      encephalopathy before listing and recipient age. A model including all these
      variables yielded a c-index of 0.851. CONCLUSIONS: Sarcopenia was associated with
      waiting list mortality in liver transplant candidates with cirrhosis,
      particularly in patients with lower MELD scores. The MELD-Sarcopenia score was
      successfully validated in this cohort. However, incorporating sarcopenia in the
      MELD score had limited added value in predicting waiting list mortality. LAY
      SUMMARY: In this study among patients with liver cirrhosis listed for liver
      transplantation, low skeletal muscle mass was associated with mortality on the
      waiting list, particularly in patients who were listed with low priority based on
      a low MELD score. However, adding these measurements to the currently used system
      for donor and organ allocation showed no added value.

PMID- 29221887
TI  - Resistance analysis in patients with genotype 1-6 HCV infection treated with
      sofosbuvir/velpatasvir in the phase III studies.
AB  - BACKGROUND & AIMS: The fixed-dose combination of sofosbuvir/velpatasvir was
      highly efficacious in patients infected with genotype (GT)1-6 hepatitis C virus
      (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline
      resistance-associated substitutions (RASs) on treatment outcome and emergence of
      RASs in patients infected with HCV GT1-6 who were treated with
      sofosbuvir/velpatasvir. METHODS: Non-structural protein 5A and 5B (NS5A and NS5B)
      deep sequencing was performed at baseline and at the time of relapse for all
      patients treated with sofosbuvir/velpatasvir for 12 weeks (n = 1,778) in the
      ASTRAL-1-3, ASTRAL-5 and POLARIS-2-3 studies. RESULTS: Patients with 37 known and
      19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to
      61% depending on genotype) had detectable NS5A class RASs at baseline, using a
      15% sequencing assay cut-off. There was no significant effect of baseline NS5A
      class RASs on sustained virologic response at week 12 (SVR12) with
      sofosbuvir/velpatasvir; the SVR12 rate in the presence of NS5A class RASs was
      100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in
      patients with GT2 and GT4-6 infections. In GT3 infection, the SVR rate was 93%
      and 98% in patients with and without baseline NS5A class RASs, respectively. The
      overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with
      sofosbuvir/velpatasvir. Single NS5A class resistance was observed at virologic
      failure in 17 of the 20 patients. CONCLUSIONS: Sofosbuvir/velpatasvir taken for
      12 weeks once daily resulted in high SVR rates in patients infected with GT1-6
      HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not
      sofosbuvir resistance, was detected in the few patients with virologic failure.
      These data highlight the high barrier to resistance of this regimen for the
      treatment of chronic HCV across all genotypes in the vast majority of patients.
      LAY SUMMARY: Sofosbuvir/velpatasvir taken once daily for 12 weeks resulted in
      high sustained virologic response rates in patients infected with HCV,
      irrespective of the presence of NS5A resistance-associated variants prior to
      treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance,
      was detected in the few patients with virologic failure. These data highlight the
      high barrier to resistance of this regimen for the treatment of chronic HCV
      across all genotypes in the vast majority of patients.

PMID- 29221889
TI  - On Exploring Vocal Ornamentation in Byzantine Chant.
AB  - OBJECTIVES: A special vocal ornament in Byzantine chant (BC), the single cycle
      ornamentation structure (SCOS), is defined and compared with the vibrato with
      respect to its time (rate, extent) and spectral (slope [SS], relative speaker's
      formant [SPF] level, formant frequencies [Fi] and bandwidths [Bi], and noise-to
      harmonics ratio [NHR]) characteristics. STUDY DESIGN: This is a comparative study
      between the vocal ornaments of SCOS and vibrato, of which time and spectral
      acoustic parameters were measured, statistically analyzed, and compared. METHODS:
      From the same hymn recordings chanted by four chanters, the SS, SPF level, FFi,
      FBi, and NHR difference values between the vocal ornament and its neighbor steady
      note, and the rate and extent, were compared with those of vibrato. RESULTS: The
      mean extent values for SCOS were found to be almost double the corresponding
      values for vibrato, and the rate of SCOS tends to be different from the rate of
      vibrato. The difference values of: 1) the NHR, 2) the spectral slope, and 3) the
      SPF level, between the vocal ornament and its neighbor steady note were found to
      be: 1) higher for SCOS, 2) mainly lower for SCOS, and 3) lower for SCOS,
      respectively. No significant differences were detected for the FFi and FBi. The
      FF1 differences tend to be negative in both ornaments indicating a formant tuning
      effect. CONCLUSIONS: A new vocal ornament (SCOS) in BC is studied, of which the
      extent, NHR (HNR), the spectral slope, and the SPF level are different compared
      to those of vibrato.

PMID- 29221891
TI  - The evolution of host defence to parasitism in fluctuating environments.
AB  - Given rapidly changing environments, it is important for us to understand how the
      evolution of host defence responds to fluctuating environments. Here we present
      the first theoretical study of evolution of host resistance to parasitism in a
      classic epidemiological model where the host birth rate varies seasonally. We
      show that this form of seasonality has clear qualitative and quantitative impacts
      on the evolution of resistance. When the host can recover from infection, it
      evolves a lower level of defence when the amplitude is high. However, when
      recovery is absent, the host increases its defence for higher amplitudes. Between
      these different behaviours we find a region of parameter space that allows
      evolutionary bistability. When this occurs, the level of defence the host evolves
      depends on initial conditions, and in some cases a switch between attractors can
      lead to different periods in the population dynamics at each of the evolutionary
      stable strategies. Crucially, we find that evolutionary behaviour found in a
      constant environment for this model doesn't always hold for hosts with highly
      variable birth rates. Hence we argue that seasonality must be taken into account
      if we want to make predictions about evolutionary trends in real-world host
      parasite systems.

PMID- 29221890
TI  - 22nd International Conference on Medical Physics 2016, Bangkok, Thailand; Medical
      physics propelling global health.
AB  - As medical technology evolves and patient needs increase, the need for well
      trained and highly professional medical physicists (MPs) becomes even more
      urgent. The roles and responsibilities of MPs in various departments within the
      hospital are diverse and demanding. It is obvious that training, continuing
      education and professional development of MPs have become essential. One of the
      ways for an MP to advance his or her knowledge is to participate in conferences
      and congresses. Last year, the 22nd International Conference of Medical Physics
      (ICMP 2016) took place in Bangkok, Thailand. The event attracted 584 delegates
      with most of the participants coming from Asia. It attracted also delegates from
      42 countries. The largest delegations were from Thailand, Japan and South Korea.
      ICMP 2016 included 367 oral presentations and e-posters, most of these being in
      the fields of Radiation Therapy, Medical Imaging and Radiation Safety. All
      abstracts were published as an e-book of Abstracts in a supplement to the
      official IOMP Journal. Many companies had exhibition stands at ICMP2016, thus
      allowing the participants to see the latest developments in the medical physics
      related industry. The conference included 42 mini-symposia, part of the first
      "IOMP School" activity, covering various topics of importance for the profession
      and this special issue follows from the success of the conference.

PMID- 29221892
TI  - Coevolution of nonlinear group interactions and strategies in well-mixed and
      structured populations.
AB  - In microbial populations and human societies, the rule of nonlinear group
      interactions strongly affects the intraspecific evolutionary dynamics, which
      leads to the variation of the strategy composition eventually. The consequence of
      such variation may retroact to the rule of the interactions. This correlation
      indicates that the rule of nonlinear group interactions may coevolve with
      individuals' strategies. Here, we develop a model to investigate such coevolution
      in both well-mixed and structured populations. In our model, positive and
      negative correlations between the rule and the frequency of cooperators are
      considered, with local and global information. When the correlation refers to the
      global information, we show that in well-mixed populations, the coevolutionary
      outcomes cover the scenarios of defector dominance, coexistence, and bi
      stability. Whenever the population structure is considered, its impact on the
      coevolutionary dynamics depends on the type of the correlation: with a negative
      (positive) correlation, population structure promotes (inhibits) the evolution of
      cooperation. Furthermore, when the correlation is based on the more accessible
      local information, we reveal that a negative correlation pushes cooperators into
      a harsh situation whereas a positive one lowers the barriers for cooperators to
      occupy the population. All our analytical results are validated by numerical
      simulations. Our results shed light on the power of the coevolution of nonlinear
      group interactions and evolutionary dynamics on generating various evolutionary
      outcomes, implying that the coevolutionary framework may be more appropriate than
      the traditional cases for understanding the evolution of cooperation in both
      structureless and structured populations.

PMID- 29221893
TI  - Cardioprotective effect of influenza and pneumococcal vaccination in patients
      with cardiovascular diseases.
AB  - Due to the wide interaction between the respiratory and the circulatory systems,
      influenza and pneumococcal vaccinations are recommended in the prevention and
      treatment of cardiovascular diseases. The review summarizes the results of recent
      studies and meta-analyses demonstrating that in this group of high-risk patients
      both vaccinations have potentially beneficial properties. However, in the era of
      Evidence Base Medicine, there is still a lack of randomized prospective clinical
      trials, especially those evaluating the effect of pneumococcal vaccination. As
      the burden of cardiovascular diseases represents various pathologies, it is
      important to point that the beneficial effect of vaccination is more pronounced
      in the atherosclerotic etiology, especially in patients after recent coronary
      events. This information contributes significantly to the appreciation of the
      role of the adaptive and innate immunity in atherosclerosis, which is now
      considered as immuno-inflammatory process driven by LDL-cholesterol intimal
      infiltration and macrophages activation. The mechanism of the cardioprotective
      effect of vaccination may not only be associated with the elimination of
      infections and their complications, but also related to the modification of the
      immuno-inflammatory model of atherosclerosis.

PMID- 29221894
TI  - Efficacy of an inactivated Mycoplasma hyorhinis vaccine in pigs.
AB  - Lameness and polyserositis in pigs caused by Mycoplasma hyorhinis are generally
      treated with antibiotics and may require multiple doses. The costs of these
      antibiotics combined with economic losses from culling and reduced feed
      conversion due to lameness are hardships to the swine producer. In this study we
      have demonstrated efficacy of an inactivated M. hyorhinis vaccine administered to
      three-week old caesarian-derived colostrum-deprived piglets. Three doses of
      vaccine (high, medium, and low) were evaluated and compared to a placebo control.
      Mycoplasma hyorhinis challenge occurred three weeks after vaccination. Pigs were
      observed for lameness and respiratory distress for three weeks following
      challenge. Pigs were then euthanized and a gross pathological evaluation for
      polyserositis and arthritis was performed. A minimum immunizing dose of vaccine
      was defined as containing at least 7.41 * 107 CCU of M. hyorhinis per 2.0 mL dose
      as represented by the medium dose vaccine. This vaccine provided significant
      reductions in lameness and pericarditis with preventive fractions of 0.76 (95% CI
      [0.26, 0.92]) and 0.58 (95% CI [0.31, 0.74]), respectively, compared to the
      placebo control group. A significant increase in post-challenge weight gain (P <
      .0001) was also achieved with this vaccine, with an average daily gain (ADG) of
      0.92 lbs/day compared to 0.57 lbs/day in the placebo group.

PMID- 29221895
TI  - Report on eighth WHO meeting on development of influenza vaccines that induce
      broadly protective and long-lasting immune responses: Chicago, USA, 23-24 August
      2016.
AB  - In August 2016, the World Health Organization (WHO) convened the "Eighth meeting
      on development of influenza vaccines that induce broadly protective and long
      lasting immune responses" to discuss the regulatory requirements and pathways for
      licensure of next-generation influenza vaccines, and to identify areas where WHO
      can promote the development of such vaccines. Participants included approximately
      120 representatives of academia, the vaccine industry, research and development
      funders, and regulatory and public health agencies. They reviewed the draft WHO
      preferred product characteristics (PPCs) of vaccines that could address
      prioritized unmet public health needs and discussed the challenges facing the
      development of such vaccines, especially for low- and middle-income countries
      (LMIC). They defined the data desired by public-health decision makers globally
      and explored how to support the progression of promising candidates into late
      stage clinical trials and for all countries. This report highlights the major
      discussions of the meeting.

PMID- 29221897
TI  - Comparative mechanical unfolding studies of spectrin domains R15, R16 and R17.
AB  - Spectrins belong to repetitive three-helix bundle proteins that have vital
      functions in multicellular organisms and are of potential value in
      nanotechnology. To reveal the unique physical features of repeat proteins we have
      studied the structural and mechanical properties of three repeats of chicken
      brain alpha-spectrin (R15, R16 and R17) at the atomic level under stretching at
      constant velocities (0.01, 0.05 and 0.1 A.ps-1) and constant forces (700 and 900
      pN) using molecular dynamics (MD) simulations at T = 300 K. 114 independent MD
      simulations were performed and their analysis has been done. Despite structural
      similarity of these domains we have found that R15 is less mechanically stable
      than R16, which is less stable than R17. This result is in agreement with the
      thermal unfolding rates. Moreover, we have observed the relationship between
      mechanical stability, flexibility of the domains and the number of aromatic
      residues involved in aromatic clusters.

PMID- 29221896
TI  - Correlative imaging reveals physiochemical heterogeneity of microcalcifications
      in human breast carcinomas.
AB  - Microcalcifications (MCs) are routinely used to detect breast cancer in
      mammography. Little is known, however, about their materials properties and
      associated organic matrix, or their correlation to breast cancer prognosis. We
      combine histopathology, Raman microscopy, and electron microscopy to image MCs
      within snap-frozen human breast tissue and generate micron-scale resolution
      correlative maps of crystalline phase, trace metals, particle morphology, and
      organic matrix chemical signatures within high grade ductal carcinoma in situ
      (DCIS) and invasive cancer. We reveal the heterogeneity of mineral-matrix
      pairings, including punctate apatitic particles (<2 um) with associated trace
      elements (e.g., F, Na, and unexpectedly Al) distributed within the necrotic cores
      of DCIS, and both apatite and spheroidal whitlockite particles in invasive cancer
      within a matrix containing spectroscopic signatures of collagen, non-collagen
      proteins, cholesterol, carotenoids, and DNA. Among the three DCIS samples, we
      identify key similarities in MC morphology and distribution, supporting a
      dystrophic mineralization pathway. This multimodal methodology lays the
      groundwork for establishing MC heterogeneity in the context of breast cancer
      biology, and could dramatically improve current prognostic models.

PMID- 29221898
TI  - Exercise merging physical and cognitive stimulation improves physical fitness and
      cognitive functioning in older nursing home residents: a pilot study.
AB  - The main purpose of this pilot study was to examine the feasibility and the
      effects of a multimodal exercise intervention on the physical and cognitive
      functioning of institutionalized older people. Twenty-one older adults (83.5 +/-
      4.9 years) living in two nursing home residences, were tested on two occasions 4
      weeks apart to establish a baseline measure, and then engage in the exercise
      program twice weekly for 8 weeks. Participants were tested again after the
      exercise program. Almost all physical fitness and cognitive tests were unchanged
      at baseline measures, but after the exercise program, significant improvements (p
      < 0.05) were found in all physical fitness variables (strength, cardiorespiratory
      endurance, flexibility and balance) and in the majority of cognitive variables
      (visual attention, executive functioning and information processing speed).
      Exercise merging physical and cognitive stimulation could have broad impacts in
      the individual's level of functioning and should be promoted in nursing home
      residences for the elderly.

PMID- 29221899
TI  - C-statistic: A brief explanation of its construction, interpretation and
      limitations.

PMID- 29221900
TI  - Editorial overview: Food biotechnology: Exploration and exploitation of microbial
      resources to address the need for sustainable production of safe, healthy and
      nutritious food.

PMID- 29221901
TI  - Role of heel lifting in standing balance recovery: A simulation study.
AB  - Although lifting the heels has frequently been observed during balance recovery,
      the function of this movement has generally been overlooked. The present study
      aimed to investigate the functional role of heel lifting during regaining balance
      from a perturbed state. Computer simulation was employed to objectively examine
      the effect of allowing/constraining heel lifting on balance performance. The
      human model consisted of 3 rigid body segments connected by frictionless joints.
      Movements were driven by joint torques depending on current joint angle, angular
      velocity, and activation level. Starting from forward-inclined and static
      straight-body postures, the optimization goal was to recover balance effectively
      (so that ground projection of the mass center returned to the inside of the base
      of support) and efficiently by adjusting ankle and hip joint activation levels.
      Allowing/constraining heel lifting resulted in virtually identical movements when
      balance was mildly perturbed at the smallest lean angle (8 degrees ). At larger
      lean angles (8.5 degrees  and 9 degrees ), heel lifting assisted balance recovery
      more evidently with larger joint movements. Partial and altered timings of
      ankle/hip torque activation due to constraining heel lifting reduced linear and
      angular momentum generation for avoiding forward falling, and resulted in
      hindered balancing performance.

PMID- 29221902
TI  - A comparison of patellofemoral cartilage morphology and deformation in anterior
      cruciate ligament deficient versus uninjured knees.
AB  - Anterior cruciate ligament (ACL) deficient patients have an increased rate of
      patellofemoral joint (PFJ) osteoarthritis (OA) as compared to the general
      population. Although the cause of post-injury OA is multi-factorial, alterations
      in joint biomechanics may predispose patients to cartilage degeneration. This
      study aimed to compare in vivo PFJ morphology and mechanics between ACL deficient
      and intact knees in subjects with unilateral ACL ruptures. Eight male subjects
      underwent baseline MRI scans of both knees. They then performed a series of 60
      single-legged hops, followed by a post-exercise MRI scan. This process was
      repeated for the contralateral knee. The MR images were converted into three
      dimensional surface models of cartilage and bone in order to assess cartilage
      thickness distributions and strain following exercise. Prior to exercise,
      patellar cartilage was significantly thicker in intact knees as compared to ACL
      deficient knees by 1.8%. In response to exercise, we observed average patellar
      cartilage strains of 5.4 +/- 1.1% and 2.5 +/- 1.4% in the ACL deficient and
      intact knees, respectively. Importantly, the magnitude of patellar cartilage
      strain in the ACL deficient knees was significantly higher than in the intact
      knees. However, while trochlear cartilage experienced a mean strain of 2.4 +/-
      1.6%, there was no difference in trochlear cartilage strain between the ACL
      deficient and uninjured knees. In summary, we found that ACL deficiency was
      associated with decreased patellar cartilage thickness and increased exercise
      induced patellar cartilage strain when compared to the uninjured contralateral
      knees.

PMID- 29221903
TI  - Discrete element analysis is a valid method for computing joint contact stress in
      the hip before and after acetabular fracture.
AB  - Evaluation of abnormalities in joint contact stress that develop after inaccurate
      reduction of an acetabular fracture may provide a potential means for predicting
      the risk of developing post-traumatic osteoarthritis. Discrete element analysis
      (DEA) is a computational technique for calculating intra-articular contact stress
      distributions in a fraction of the time required to obtain the same information
      using the more commonly employed finite element analysis technique. The goal of
      this work was to validate the accuracy of DEA-computed contact stress against
      physical measurements of contact stress made in cadaveric hips using Tekscan
      sensors. Four static loading tests in a variety of poses from heel-strike to toe
      off were performed in two different cadaveric hip specimens with the acetabulum
      intact and again with an intentionally malreduced posterior wall acetabular
      fracture. DEA-computed contact stress was compared on a point-by-point basis to
      stress measured from the physical experiments. There was good agreement between
      computed and measured contact stress over the entire contact area (correlation
      coefficients ranged from 0.88 to 0.99). DEA-computed peak contact stress was
      within an average of 0.5 MPa (range 0.2-0.8 MPa) of the Tekscan peak stress for
      intact hips, and within an average of 0.6 MPa (range 0-1.6 MPa) for fractured
      cases. DEA-computed contact areas were within an average of 33% of the Tekscan
      measured areas (range: 1.4-60%). These results indicate that the DEA methodology
      is a valid method for accurately estimating contact stress in both intact and
      fractured hips.

PMID- 29221904
TI  - Tensile behaviour of individual fibre bundles in the human lumbar anulus
      fibrosus.
AB  - Disc degeneration is a common medical affliction whose origins are not fully
      understood. An improved understanding of its underlying mechanisms could lead to
      the development of more effective treatments. The aim of this paper was to
      investigate the effect of (1) degeneration, (2) circumferential region and (3)
      strain rate on the microscale mechanical properties (toe region modulus, linear
      modulus, extensibility, phase angle) of individual fibre bundles in the anulus
      fibrosus lamellae of the human intervertebral disc. Healthy and degenerate fibre
      bundles excised from different circumferential regions in the outer anulus
      (posterolateral, lateral, anterolateral, anterior) were tensile tested at slow
      (0.1%/s), medium (1%/s) and fast (10%/s) strain rates using a micromechanical
      testing system. Our preliminary results showed that neither degeneration nor
      circumferential region significantly affected the fibre bundles' mechanical
      behaviour. However, when the fibre bundles were tested at higher strain rates,
      this resulted in significantly higher linear moduli and lower phase angles. These
      findings, compared with data from other studies investigating single and multiple
      lamellae sections, suggest that degeneration has minimal effect on outer anulus
      mechanics irrespective of structural level, and the inter- and intra-lamellar
      arrangement and continuity of the fibre bundles may influence the lamellae's
      regional behaviour and viscoelasticity.

PMID- 29221905
TI  - Neurexins and neuropsychiatric disorders.
AB  - Neurexins are a family of presynaptic single-pass transmembrane proteins that act
      as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1,
      NRXN2, and NRXN3), each of which produces a longer alpha- and shorter beta-form.
      Genomic alterations in NRXN genes have been identified in a wide variety of
      neuropsychiatric disorders, including autism spectrum disorders (ASD),
      schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi
      allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome. The
      fact that some mono-allelic functional variants of NRXNs are also found in
      healthy controls indicates that other genetic or environmental factors affect the
      penetrance of NRXN deficiency. In this review, we summarize the common research
      methods and representative results of human genetic studies that have implicated
      NRXN variants in various neuropsychiatric disorders. We also summarize studies of
      rodent models with NRXN deficiencies that complement our knowledge of human
      genetics.

PMID- 29221907
TI  - Coupling of exocytosis and endocytosis at the presynaptic active zone.
AB  - Brain function depends on the ability of neurons to communicate with each other
      via the regulated exocytosis of neurotransmitter-containing synaptic vesicles
      (SVs) at specialized presynaptic release sites termed active zones (AZs). The
      presynaptic AZ comprises an assembly of large multidomain proteins that link the
      machinery for vesicle fusion to sites of voltage-dependent Ca2+ entry. Following
      SV fusion at AZ release sites SV membranes are retrieved by compensatory
      endocytosis, and SVs are reformed. Recent data suggest that Ca2+-triggered SV
      exocytosis at AZs and endocytic retrieval of SVs may be functionally and
      physically linked. Here we discuss the evidence supporting such exo-endocytic
      coupling as well as possible modes and mechanisms that may underlie coupling of
      exocytosis and endocytosis at and around AZs in presynaptic nerve terminals. As
      components of the exo-endocytic machinery at synapses have been linked to
      neurological and neuropsychiatric disorders, understanding the mechanisms that
      couple exocytosis and endocytosis at AZs may be of importance for developing
      novel therapies to treat these diseases.

PMID- 29221908
TI  - How to maintain active zone integrity during high-frequency transmission.
AB  - In the central nervous system, the frequency at which reliable synaptic
      transmission can be maintained varies strongly between different types of
      synapses. Several pre- and postsynaptic processes must interact to enable high
      frequency synaptic transmission. One of the mechanistically most challenging
      issues arises during repetitive neurotransmitter release, when synaptic vesicles
      fuse in rapid sequence with the presynaptic plasma membrane within the active
      zone (AZ), potentially interfering with the structural integrity of the AZ
      itself. Here we summarize potential mechanisms that help to maintain AZ
      integrity, including arrangement and mobility of release sites, calcium channel
      mobility, as well as release site clearance via lateral diffusion of vesicular
      proteins and via endocytotic membrane retrieval. We discuss how different types
      of synapses use these strategies to maintain high-frequency synaptic
      transmission.

PMID- 29221909
TI  - Maintaining the active zone: Demand, supply and disposal of core active zone
      proteins.
AB  - Chemical synapses are sites of cell-cell contact specialized for transmission of
      signals between neurons and their respective targets. Neurotransmission occurs
      through the secretion of neurotransmitters at specialized presynaptic membrane
      regions known as Active Zones (AZs). AZ composition and function are now
      characterized quite well. Much less is known, however, on the manners by which
      these unique specializations are maintained for weeks, months, and presumably
      years. Here we focus on core AZ components that make up the Cytoskeleton
      associated with the AZ (CAZ) - their lifetimes, their supply and their disposal.
      We describe recent findings on CAZ molecule turnover rates, on the synthesis and
      trafficking of CAZ molecules to synapses and on the manners by which they are
      degraded. We highlight converging findings, point to discrepancies, in particular
      related to temporal and spatial constraints, and try to reconcile these, where
      possible, by offering more inclusive interpretations.

PMID- 29221906
TI  - Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture
      and selective impairments in aging.
AB  - Neurotransmitter release occurs at active zones, which are specialized regions of
      the presynaptic membrane. A dense collection of proteins at the active zone
      provides a platform for molecular interactions that promote recruitment, docking,
      and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs),
      muscle-derived laminin beta2 interacts with presynaptic voltage-gated calcium
      channels to organize active zones. The molecular architecture of presynaptic
      active zones has been revealed using super-resolution microscopy techniques that
      combine nanoscale resolution and multiple molecular identification.
      Interestingly, the active zones of adult NMJs are not stable structures and thus
      become impaired during aging due to the selective degeneration of specific active
      zone proteins. This review will discuss recent progress in the understanding of
      active zone nanoarchitecture and the mechanisms underlying active zone
      organization in mammalian NMJs. Furthermore, we will summarize the age-related
      degeneration of active zones at NMJs, and the role of exercise in maintaining
      active zones.

PMID- 29221910
TI  - Motor cortex Transcranial Direct Current Stimulation (tDCS) improves acute stroke
      visuo-spatial neglect: A series of four case reports.

PMID- 29221911
TI  - Circulating cardiodepressant factors in takotsubo syndrome: An "angle" that needs
      to be explored further.

PMID- 29221912
TI  - Variable clinical phenotype in two siblings with Aicardi-Goutieres syndrome type
      6 and a novel mutation in the ADAR gene.
AB  - Aicardi-Goutieres syndrome (AGS) is a hereditary inflammatory encephalopathy
      resulting in severe neurological damage in the majority of cases. We report on
      two siblings with AGS6 due to compound heterozygosity for a known and a novel
      mutation in the ADAR gene and a strikingly variable phenotype. The first sibling
      presented at 12 months of age with a subacute encephalopathy following a mild
      respiratory infection. The child developed a spastic tetraparesis, generalized
      dystonia and dysarthria. In contrast, the younger sibling presented with an acute
      episode of neurological impairment in his third year of life, from which he
      recovered without sequelae within a few weeks. These findings illustrate a
      striking intrafamilial phenotypic variability in patients with AGS6 and describe
      the first case of a full recovery from an acute encephalopathy in an AGS patient.
      Our findings also suggest that AGS should be considered as an important
      differential diagnosis of an infection-triggered encephalopathy in infancy
      despite the absence of typical neuroimaging findings.

PMID- 29221913
TI  - Facial asymmetry correction with moulded helmet therapy in infants with
      deformational skull base plagiocephaly.
AB  - PURPOSE: The recommendation issued by the American Academy of Pediatrics in the
      early 1990s to position infants on their back during sleep to prevent sudden
      infant death syndrome (SIDS) has dramatically reduced the number of deaths due to
      SIDS but has also markedly increased the prevalence of positional skull
      deformation in infants. Deformation of the base of the skull occurs predominantly
      in very severe deformational plagiocephaly and is accompanied by facial
      asymmetry, as well as an altered ear position, called ear shift. Moulded helmet
      therapy has become an accepted treatment strategy for infants with deformational
      plagiocephaly. The aim of this study was to determine whether facial asymmetry
      could be corrected by moulded helmet therapy. MATERIALS AND METHODS: In this
      retrospective, single-centre study, we analysed facial asymmetry of 71 infants
      with severe deformational plagiocephaly with or without deformational
      brachycephaly who were undergoing moulded helmet therapy between 2009 and 2013.
      Computer-assisted, three-dimensional, soft-tissue photographic scanning was used
      to record the head shape before and after moulded helmet therapy. The distance
      between two landmarks in the midline of the face (i.e., root of the nose and
      nasal septum) and the right and left tragus were measured on computer-generated
      indirect and objective 3D photogrammetry images. A quotient was calculated
      between the two right- and left-sided distances to the midline. Quotients were
      compared before and after moulded helmet therapy. Infants without any therapy
      served as a control group. RESULTS: The median age of the infants before onset of
      moulded helmet therapy was 5 months (range 3-16 months). The median duration of
      moulded helmet therapy was 5 months (range 1-16 months). Comparison of the pre-
      and post-treatment quotients of the left vs. right distances measured between the
      tragus and root of the nose (n = 71) and nasal septum (n = 71) revealed a
      significant reduction of the asymmetry (Tragus-Nasion-Line Quotient: 0.045-0.022;
      p < 0.0001; Tragus-Subnasale-Line Quotient: 0.045-0.021; p < 0.0001). The control
      group without treatment showed no significant change in the quotient (Tragus
      Nasion-Line Quotient no helmet: 0.049-0.055/Tragus-Subnasale-Line Quotient no
      helmet: 0.039-0.055). CONCLUSION: Moulded helmet therapy can correct facial
      symmetry in infants with deformational plagiocephaly and associated facial and
      basal skull asymmetry.

PMID- 29221914
TI  - Microalgae as feedstock for biodiesel production under ultrasound treatment - A
      review.
AB  - The application of ultrasound in biodiesel production has recently emerged as a
      novel technology. Ultrasound treatment enhances the mass transfer characteristics
      leading to the increased reaction rate with short reaction time and potentially
      reduces the production cost. In this review, application of ultrasound-assisted
      biodiesel production using acid, base and enzyme catalysts is presented. A
      critical assessment of the current status of ultrasound in biodiesel production
      was discussed with the emphasis on using ultrasound for efficient microalgae
      biodiesel production. The ultrasound in the biodiesel production enhances the
      emulsification of immiscible liquid reactant by microturbulence generated by
      cavitation bubbles. The major benefit of the ultrasound-assisted biodiesel
      production is a reduction in reaction time. Several different methods have been
      discussed to improve the biodiesel production. Overall, this review focuses on
      the current understanding of the application of ultrasound in biodiesel
      production from microalgae and to provide insights into future developments.

PMID- 29221916
TI  - DNA methylation signatures at endoplasmic reticulum stress genes are associated
      with adiposity and insulin resistance.
AB  - A sustained activation of the unfolded protein response and the subsequent
      endoplasmic reticulum (ER) stress has been involved in the onset and severity of
      several metabolic diseases. The aim of this study was to analyze the association
      of DNA methylation signatures at ER stress genes with adiposity traits and
      related metabolic disorders. An epigenomic analysis within the Methyl Epigenome
      Network Association (MENA) project was conducted in an adult population (n=474).
      DNA methylation status in peripheral white blood cells was analyzed by a
      microarray approach. KEGG database was used to the characterization and
      discrimination of genes involved in the "protein processing in endoplasmic
      reticulum pathway". Anthropometric measurements and plasma metabolic profiles
      were analyzed. A total of 15 CpG sites at genes participating in ER pathway were
      strongly correlated with BMI after adjusted linear regression analyses
      (p<0.0001). These included cg08188400 (MAP2K7), cg20541779 (CASP12), cg24776411
      (EIF2AK1), cg14190817 (HSPA5), cg21376454 (ERN1), cg06666486 (EIF2AK1),
      cg03211481 (DNAJC1), cg18357645 (OS9), cg05801879 (MBTPS1), cg20964082 (ERO1LB),
      cg17300868 (NFE2L2), cg03384128 (EIF2AK4), cg02712587 (EIF2AK4), cg04972384
      (SELS), cg02240686 (EIF2AK2). Noteworthy, most of them were implicated in ER
      stress (p=2.9E-09). However, only methylation levels at cg20964082 (ERO1LB),
      cg17300868 (NFE2L2), cg05801879 (MBTPS1), and cg03384128 (EIF2AK4) also
      correlated with total fat mass. Interestingly, significant associations between
      methylation patterns at cg20964082 (ERO1LB) and cg17300868 (NFE2L2) and insulin
      and HOMA-IR index were found, whereas cg05801879 (MBTPS1) and cg03384128
      (EIF2AK4) were correlated with triglyceride levels. This study suggests
      associations of methylation signatures at ER stress genes with adiposity and
      insulin resistance, as revealed by discriminative pathway analyses.

PMID- 29221917
TI  - The distal airway microbiome after lung transplantation: A driver of immune
      regulation?

PMID- 29221915
TI  - Structural brain development: A review of methodological approaches and best
      practices.
AB  - Continued advances in neuroimaging technologies and statistical modelling
      capabilities have improved our knowledge of structural brain development in
      children and adolescents. While this has provided an increasingly nuanced
      understanding of brain development, the field is still plagued by inconsistent
      findings. This review highlights the methodological diversity in existing
      longitudinal magnetic resonance imaging (MRI) studies on structural brain
      development during childhood and adolescence, and addresses how such variation
      might contribute to inconsistencies in the literature. We discuss the impact of
      method choices at multiple decision points across the research process, from
      study design and sample selection, to image processing and statistical analysis.
      We also highlight the extent to which different methodological considerations
      have been empirically examined, drawing attention to specific areas that would
      benefit from future investigation. Where appropriate, we recommend certain best
      practices that would be beneficial for the field to adopt, including greater
      completeness and transparency in reporting methods, in order to ultimately
      develop an accurate and detailed understanding of normative child and adolescent
      brain development.

PMID- 29221918
TI  - Low Variability in Peak Expiratory Flow Predicts Successful Inhaled
      Corticosteroid Step-Down in Adults with Asthma.
AB  - BACKGROUND: The prognosis for patients beyond 1 year after reduction of their
      inhaled corticosteroid (ICS) dose remains unknown. Predictive factors that can be
      evaluated before the initiation of asthma treatment or at ICS dose reduction are
      unknown. METHODS: We prospectively studied 223 patients in 6 hospitals in the
      National Hospital Organization of Japan during the 36 months after 50% reduction
      of their daily ICS dose. All patients recorded their morning and evening peak
      expiratory flows (PEFs) in their diaries. Lung function, bronchial
      hyperresponsiveness, fractional nitric oxide levels, number of eosinophils in
      sputum, and serum IgE levels were measured in most patients. Serum levels of IL
      10, IL-33, and thymic stromal lymphopoietin before ICS dose reduction were
      measured in all patients. RESULTS: During the 36-month study period, asthma
      control was retained in 127 (59.6%) of the 213 enrolled patients who underwent
      ICS dose reduction. Multivariate logistic regression analysis revealed that, at
      the initiation of dose reduction, the factors most predictive of maintenance of
      asthma control after ICS dose reduction were a low serum IL-33 level (P < .01),
      low PEF variability over 1 week (P = .014), childhood onset of asthma (at age <10
      years) (P = .03), and high serum IL-10 level (P = .035). CONCLUSIONS: We
      demonstrated that low PEF variability over 1 week, high serum IL-10 level, and
      low serum IL-33 concentration were useful factors for predicting that an adult's
      asthma will remain in control for months to years after a 50% reduction in the
      daily ICS dose.

PMID- 29221920
TI  - Treatment of Infected Aneurysm with Combined Endovascular Aneurysm Repair and
      Abscess Drainage.
AB  - PURPOSE: To evaluate the clinical utility of combination therapy with
      endovascular aneurysm repair (EVAR) and abscess drainage for the treatment of
      infected aneurysms. MATERIALS AND METHODS: Between July 2009 and May 2015, 8
      patients underwent combination therapy with EVAR and abscess drainage. There were
      5 men and 3 women, with a mean age of 75 years +/- 7. Aneurysms were of the
      thoracic aorta in 5 patients, the abdominal aorta in 2, and the internal iliac
      artery in 1. Four patients had concurrent infection, including pyelonephritis in
      2, pelvic abscess in 1, and suppurative knee arthritis in 1. Three patients had
      ruptured aneurysms. Abscess drainage was performed percutaneously under computed
      tomographic guidance in 5 patients, thoracoscopic guidance in 2, and both in 1.
      RESULTS: Six patients (75%) were discharged without additional intervention
      except for antibiotic therapy, and the other 2 patients (25%) underwent open
      repair to control infection and to repair endoleak, respectively. There were no
      in-hospital deaths. During the mean follow-up period of 48 months +/- 22, all
      patients were alive except for 1 patient who died of recurrence of rectal cancer
      at 51 months. There were no aorta- or artery-related adverse events. Overall
      survival rates at 1 and 5 years were 100% and 80%, respectively. Aneurysm-related
      event-free rates at 1 and 5 years were 75%. CONCLUSIONS: Combination therapy with
      EVAR and abscess drainage for the treatment of infected aneurysms seems to be a
      promising strategy as an alternative or "bridge" to open surgery.

PMID- 29221919
TI  - Impact of Lifestyle Interventions Targeting Healthy Diet, Physical Activity, and
      Weight Loss on Asthma in Adults: What Is the Evidence?
AB  - Unhealthy lifestyle factors such as poor diet quality, sedentary lifestyle, and
      obesity are associated with negative health consequences in asthma including poor
      asthma control, impaired quality of life, and greater health care utilization.
      Lifestyle modification is the cornerstone of behavioral treatments and has been
      effective in chronic diseases such as atherothrombotic vascular disease and
      diabetes. There is a critical need for lifestyle interventions in asthma care
      that address obesity and its intimately linked risk behaviors in terms of poor
      diet and physical inactivity. We present in this commentary the promising
      lifestyle interventions emerging in asthma care that target poor diet, physical
      inactivity and weight loss, the proposed mechanisms of these lifestyle
      interventions, and the critical need for guideline-concordant lifestyle
      interventions in asthma care.

PMID- 29221921
TI  - Ethanol Embolotherapy for the Management of Refractory Chronic Skin Ulcers Caused
      by Arteriovenous Malformations.
AB  - PURPOSE: To describe the clinical features and treatment outcomes of ethanol
      embolotherapy in refractory chronic skin ulcers caused by arteriovenous
      malformations (AVMs). MATERIALS AND METHODS: From October 2011 to October 2015,
      12 patients (5 male; mean age, 26.2 y) with refractory chronic skin ulcers caused
      by AVMs were treated at a single institution. Ethanol embolotherapy was performed
      by direct puncture techniques. Needles were directly inserted toward the nidus of
      the lesion based on imaging analysis. When fast blood reflux was noted,
      angiography was performed to ensure only the nidus and draining vein were
      opacified. Symptoms before and after treatment, previous treatment of AVMs and
      ulcers, embolotherapy sessions, follow-up time, complications, and degree of
      devascularization were recorded. Treatment outcomes were established by
      evaluating symptom outcomes and the degree of devascularization on follow-up
      angiography. RESULTS: Fifty embolotherapy procedures were performed in 12
      patients: 6 underwent procedures on the head and neck, 4 on the feet, and 2 on
      the hands. Four patients (33.3%) experienced complete resolution of abnormal
      angioarchitecture according to follow-up angiography. Complete control of ulcers
      was achieved in all 12 patients. Two procedures (4%) in 2 patients (16.7%) caused
      superficial skin necrosis that healed spontaneously within 4 weeks. Thirteen
      procedures (26%) in 9 patients (75%) caused blistering immediately after
      treatment. There were no major complications. CONCLUSIONS: In a limited series,
      ethanol embolotherapy was effective and safe in the treatment of refractory
      chronic skin ulcers caused by AVMs.

PMID- 29221922
TI  - Pediatric Percutaneous Nephrostomy: A Multicenter Experience.
AB  - PURPOSE: To analyze technique, outcomes, and complications of a large series of
      pediatric percutaneous nephrostomy (PCN) procedures performed at 4 tertiary
      pediatric centers. MATERIALS AND METHODS: Retrospective multicenter study of PCNs
      performed during an 11-year period. Six hundred seventy-five PCNs were performed
      on 441 patients (median age: 4 y, range: 1 d-18 y, median weight: 17 kg, range:
      0.7-112 kg); 31% were younger than 1 year. The most frequent indications for PCN
      procedures included hydronephrosis (57%), calculus (14%), and infection (12%).
      Forty-five percent of patients had severe and 32% had moderate hydronephrosis.
      RESULTS: Technical success was 99% (n = 668); 7 failures occurred from lost
      access, during tract dilatation (n = 5) and during staghorn calculi without
      dilatation (n = 2). General anesthesia was used in 73% of procedures. Combined
      ultrasound and fluoroscopy was used in 98% of procedures. Of the 668 procedures,
      561 (84%) were primary nephrostomy insertions, and 107 (16%) were a variety of
      exchanges (secondary catheter insertions). Twenty-four of 675 (4%) were
      transplanted kidneys. Access sites included lower (47%), mid (28%), and upper
      (12%) poles and pelvis (11%). Catheters were predominantly 7-8 French (n = 352).
      The mean catheter dwell time was 25 days (0-220 d). Total primary catheter days
      were 14,482, with an additional 2,241 days after secondary procedures. Follow-up
      in 653/668 (98%) procedures documented elective removal (79%) and salvage
      procedures (21%), which included wire exchange (8.7%), nephroureteral
      stent/catheter conversion (8.8%), and tube upsizing (3.5%). Periprocedural
      complications occurred in 30/668 (4.5%) procedures: 1 major (0.1%) self-limiting
      hematuria requiring transfusion and 29 (4.4%) minor complications. CONCLUSIONS:
      PCN is safe and successful in children of all ages, with few major complications.
      PCN in children is associated with specific technical challenges and requires
      ongoing management tailored to the very young to achieve good outcomes.

PMID- 29221923
TI  - Combination of Neoadjuvant Transcatheter Arterial Chemoembolization and
      Orthotopic Liver Transplantation for the Treatment of Cirrhotomimetic
      Hepatocellular Carcinoma.
AB  - PURPOSE: To examine differences in outcome and response of cirrhotomimetic (CMM)
      hepatocellular carcinoma (HCC) to a combination of bridging transcatheter
      arterial chemoembolization and orthotopic liver transplantation (OLT) compared
      with non-CMM HCC. MATERIALS AND METHODS: All patients with pathologically proven
      CMM HCC who underwent bridging transcatheter arterial chemoembolization before
      OLT between 2007 and 2013 (n = 23) were retrospectively compared with a control
      group of patients with pathologically proven non-CMM HCC (n = 46). RESULTS: There
      were 29 tumors in the CMM HCC group and 64 tumors in the non-CMM group identified
      and treated. Objective response rate on MR imaging at 1 and 3 months after
      transcatheter arterial chemoembolization for CMM HCC tumors (including patients
      with complete and partial response) was 93.1% and 86.4% compared with 85.2% and
      93.2% for non-CMM tumors without statistically significant difference (P = .54
      and P = .09, respectively). Pathologic study of liver explants showed complete
      tumor necrosis in 62.3% of non-CMM tumors (38/61) compared with 10.3% of CMM
      tumors (3/29) (P < .0001). Overall 2-year survival after transcatheter arterial
      chemoembolization and OLT was significantly lower for patients with CMM HCC
      compared with patients non-CMM HCC (65.2% vs 87%, P = .03). Patients with CMM HCC
      with extranodular tumor extension involving > 50% of liver parenchyma had worse
      survival with mean 2-year survival of 402 days +/- 102 vs 656 days +/- 39 for the
      remaining patients with CMM HCC (P = .02). CONCLUSIONS: Despite similar early
      imaging response rates, CMM HCC tumors had markedly lower rates of complete
      pathologic necrosis on liver explants and were associated with reduced survival
      after OLT compared with conventional HCCs.

PMID- 29221925
TI  - Detecting protein aggregation and interaction in live cells: A guide to number
      and brightness.
AB  - The possibility to detect and quantify protein-protein interactions with good
      spatial and temporal resolutions in live cells is crucial in biology. Number and
      brightness is a powerful approach to detect both protein
      aggregation/desegregation dynamics and stoichiometry in live cells. Importantly,
      this technique can be applied in commercial set ups: both camera based and laser
      scanning microscopes. It provides pixel-by-pixel information on protein
      oligomeric states. If performed with two colours, the technique can retrieve the
      stoichiometry of the reaction under study. In this review, we discuss the
      strengths and weaknesses of the technique, stressing which are the correct
      acquisition parameters for a given microscope, the main challenges in analysis,
      and the limitations of the technique.

PMID- 29221926
TI  - Plasma protein profiling of patients with intraductal papillary mucinous neoplasm
      of the pancreas as potential precursor lesions of pancreatic cancer.
AB  - Efforts for the early diagnosis of the pancreatic ductal adenocarcinoma (PDAC)
      have recently been driven to one of the precursor lesions, namely intraductal
      papillary mucinous neoplasm of the pancreas (IPMN). Only a few studies have
      focused on IPMN molecular biology and its overall progression to cancer.
      Therefore, IPMN lacks comprehensive characterization which makes its clinical
      management controversial. In this study, we characterized plasma proteins in the
      presence of IPMNs in comparison to healthy controls, chronic pancreatitis, and
      PDAC by a proteomics approach using data-independent acquisition based mass
      spectrometry. We describe several protein sets that could aid IPMN diagnosis, but
      also differentiation of IPMN from healthy controls, as well as from benign and
      malignant diseases. Among all, high levels of carbonic anhydrases and hemoglobins
      were characteristic for the IPMN group. By employing ELISA based quantification
      we validated our results for human tissue inhibitor of metalloproteinase
      inhibitor 1 (TIMP-1). We consider IPMN management directed towards an early
      potential cancer development a crucial opportunity before PDAC initiation and
      thus its early detection and cure.

PMID- 29221927
TI  - ST2 as a novel prognostic marker in end-stage renal disease patients on
      hemodiafiltration.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) are prone to severe
      heart failure (HF) and to several life-threatening events. Therefore, the ability
      to assess disease prognosis and the risk of short-term events or death is of
      great importance. The role of soluble ST2 (sST2) as a potential new prognostic
      marker in ESRD patients is not yet known. The aim of our study was to assess the
      prognostic value of sST2 in ESRD patients on hemodiafiltration (HDF) and compare
      it with NT-proBNP, an established prognostic marker for HF and renal disease.
      METHODS: 123 ESRD patients on HDF were prospectively followed up from the date of
      the sST2/NT-proBNP measurement until their death or maximally up to 829days.
      Patients were divided into a low sST2 group (<35ng/mL) or a high sST2 group
      (>=35ng/mL) according to their measured sST2 concentration at the start of the
      study. Kaplan-Meier survival curves, Cox regression model and ROC analyses were
      used in statistical analysis. RESULTS: During follow-up 32 (26.0%) patients died
      (all cause mortality). Median (IQR) sST2 serum concentrations of survivors and
      deceased were 26 (24-29) and 36 (28-59) ng/mL, respectively. The Kaplan-Meier
      survival analysis showed that survival rate of the high sST2 group was
      statistically significant lower than of the low sST2 group (P<0.01). Cox
      regression model for sST2, using a dichotomized (cut-off=35ng/mL, hazard ratio
      (HR) (95%CI)=2.72 (1.50-4.90), P=0.001) and continuous approach with log
      transformed values in univariate (HR (95%CI)=17.35 (4.84-62.22), P<0.001) and
      multivariate analysis (HR (95%CI)=7.19 (1.89-27.38), P=0.004) showed that sST2
      alone and in combination with NT-proBNP can predict all cause mortality.
      CONCLUSIONS: sST2 has confirmed prognostic value and is independent of renal
      function and of HDF treatment. It could be useful independent prognostic marker
      for stratifying ESRD patients on HDF at high risk for life-threatening events,
      hospitalisation and death, especially in combination with NT-proBNP.

PMID- 29221924
TI  - Unraveling co-translational protein folding: Concepts and methods.
AB  - Advances in techniques such as nuclear magnetic resonance spectroscopy, cryo
      electron microscopy, and single-molecule and time-resolved fluorescent approaches
      are transforming our ability to study co-translational protein folding both in
      vivo in living cells and in vitro in reconstituted cell-free translation systems.
      These approaches provide comprehensive information on the spatial organization
      and dynamics of nascent polypeptide chains and the kinetics of co-translational
      protein folding. This information has led to an improved understanding of the
      process of protein folding in living cells and should allow remaining key
      questions in the field, such as what structures are formed within nascent chains
      during protein synthesis and when, to be answered. Ultimately, studies using
      these techniques will facilitate development of a unified concept of protein
      folding, a process that is essential for proper cell function and organism
      viability. This review describes current methods for analysis of co-translational
      protein folding with an emphasis on some of the recently developed techniques
      that allow monitoring of co-translational protein folding in real-time.

PMID- 29221928
TI  - Momentary assessment of impulsive choice and impulsive action: Reliability,
      stability, and correlates.
AB  - Impulsivity is associated with substance use, including tobacco use. The degree
      to which impulsivity fluctuates over time within persons, and the degree to which
      such intra-individual changes can be measured reliably and validly in ambulatory
      assessments is not known, however. The current study evaluated two novel
      ambulatory measures of impulsive choice and impulsive action. Impulsive choice
      was measured with an eight-item delay discounting task designed to estimate the
      subjective value of delayed monetary rewards. Impulsive action was measured with
      a two-minute performance test to assess behavioral disinhibition (the inability
      to inhibit a motor response when signaled that such a response will not be
      rewarded). Valid data on impulsive choice were collected at 70% of scheduled
      reports and valid data on impulsive action were collected on 55% of scheduled
      reports, on average. Impulsive choice and action data were not normally
      distributed, but models of relations of these measures with within- and between
      person covariates were robust across distributional assumptions. Intra-class
      correlations were substantial for both impulsive choice and action measures.
      Between persons, random intercepts in impulsive choice and action were
      significantly related to laboratory levels of their respective facets of
      impulsivity, but not self-reported or other facets of impulsivity. Validity of
      the ambulatory measures is supported by associations between abstinence from
      smoking and increased impulsivity, but challenged by an association between
      strong temptations to smoke and reduced impulsive choice. Results suggest that
      meaningful variance in impulsive choice and action can be captured using
      ambulatory methods, but that additional measure refinement is needed.

PMID- 29221929
TI  - Use of pharmacy technicians in elements of medication therapy management
      delivery: A systematic review.
AB  - BACKGROUND: Documented barriers to Medication Therapy Management (MTM) delivery,
      such as limited time and inefficient workflow may be overcome by utilizing
      support staff for administrative services. However, it is unknown how pharmacy
      technicians have been historically utilized to assist pharmacists in MTM
      delivery. OBJECTIVE: To characterize literature describing pharmacy technicians'
      participation in actions commonly undertaken in the provision of MTM services.
      METHODS: In August 2016, a PubMed (MEDLINE) and Journal of Pharmacy Technology
      search was conducted using the term "pharmacy technician" with services outlined
      within the MTM Core Elements Version 2.0, and with terms related to
      administrative actions in the provision of MTM. References were searched using
      identified studies. Eligible articles described pharmacy technicians' performance
      and/or assistance in at least one MTM Core Element or related administrative
      action to the provision of MTM. Data was independently extracted by two
      researchers; any variation in extraction was reconciled via with discussion until
      consensus reached. A standardized data extraction template was used. RESULTS:
      Forty-four manuscripts were included. Manuscripts were most likely to describe
      pharmacy technicians' assistance with medication reconciliation (70%),
      documentation (41%) and medication therapy review (30%). Actions least likely to
      be described included personal medication record development (5%), physical
      assessment (5%), follow-up (2%), and medication action plan development (0%).
      Most articles were written in the United States (73%), or Europe (16%), while the
      remaining articles were Canadian (11%); no articles were found originating from
      Asia, Africa, Australia or the Middle East. CONCLUSION: Pharmacy technicians are
      utilized most often to support MTM through assistance in medication
      reconciliation. Standardized training for pharmacy technicians that delineates
      administrative support from pharmacists' role of clinical decision making could
      help pharmacists obtain greater efficiency in MTM delivery.

PMID- 29221930
TI  - In vitro effect of Chrysosporium indicum and Chrysosporium keratinophylum on
      Toxocara canis eggs.
AB  - The degree of antagonism exercised by fungi on geohelminth development varies
      according to the morphological alterations caused by different fungal species.
      Saprophytic fungi may exert ovicidal or ovistatic effects. The aim of this study
      was to apply scanning electron microscopy (SEM) to observe the action of two soil
      saprophytic species of Chrysosporium (C. indicum and C. keratinophylum) on
      Toxocara canis eggs. The fungal strains to be tested were incubated for 28 days
      at 28 degrees C in 2% water agar with a suspension of unembryonated T. canis
      eggs. A suspension of T. canis eggs in 2% water agar was used as control group.
      The assay was done in triplicate for each fungus and the control group. SEM
      observations were performed on the 4th, 7th, 14th, 21st, and 28th day after
      inoculation. The effect of the fungi on eggs was evaluated in accordance with the
      alterations observed on the surface and the changes in the normal characteristics
      of the eggs. Hyphae around the eggs, appresoria penetrating the shell and changes
      in the typical egg membrane were observed in this assay. Type 3 effect
      (alterations that occur both in the embryo and the shell, and hyphal penetration
      of the eggs) was the prevalent effect. SEM allowed us to observe clearly the
      morphological alterations in T. canis eggs due to the effect of C. indicum and C.
      keratinophylum. Both saprophytic species of Chrysosporium alter the egg structure
      and alterations increase as exposure increases.

PMID- 29221931
TI  - Urethral Rest with Suprapubic Cystostomy for Obliterative or Nearly Obliterative
      Urethral Strictures: Urethrographic Changes and Implications for Management.
AB  - PURPOSE: Precise preoperative characterization of urethral stricture is important
      for surgical planning. A period of urethral rest by a suprapubic cystostomy tube
      may aid in stricture characterization and affect the surgical approach. In this
      study fellowship trained reconstructive urologists compared the radiographic
      characterization of anterior urethral strictures before and after a period of
      urethral rest. We then determined how this changed the planned operative
      approach. MATERIALS AND METHODS: We queried our prospectively maintained
      urethroplasty database at our institution for men with an anterior urethral
      stricture who underwent retrograde urethrogram and voiding cystourethrogram
      before and after preoperative suprapubic cystostomy tube placement. A total of 29
      men were identified for analysis. To minimize responder fatigue 20 pairs of
      radiographs were selected at random. All images before and after suprapubic tube
      placement were interpreted in random order by 11 fellowship trained
      reconstructive urologists. Interpretation included stricture length, diameter,
      location and surgeon operative plan. Preplacement and post-placement results were
      compared. Post-placement stricture length was also compared to intraoperative
      length. ICC was used to evaluate homogeneity among the urologists. Linear
      regression analysis was performed to determine the association of post
      radiographic length after tube placement with intraoperative stricture length.
      RESULTS: Imaging agreement among interpreting urologists was satisfactory (ICC
      0.72). There was no statistically significant difference in stricture length
      before vs after suprapubic tube placement. Of the images 23% were considered
      obliterative before tube placement while 58% were obliterative after placement (p
      = 0.0005). Mean +/- SD post-placement radiographic and intraoperative stricture
      length was 3.0 +/- 2.6 and 3.8 +/- 3.3 cm, respectively (p <0.0001). Deviation
      between the radiographic and intraoperative lengths increased with stricture
      length (slope 0.26, p = 0.0023). The surgeon operative plan changed 47% of the
      time, including to an excision approach in 37% of cases. CONCLUSIONS: Despite
      optimal urethral imaging with a suprapubic tube in men with high grade stricture
      reconstructive urologists underestimated length by an average of almost 1 cm.
      This underestimation was less for shorter strictures and it increased with
      stricture length. In addition, a period of urethral rest resulted in more
      frequent stricture obliteration, which was associated with a change in the
      planned operative approach about half of the time. If urologists do not place a
      suprapubic cystostomy tube prior to urethroplasty for high grade stricture, the
      operative plan should account for the stricture being tighter than it may appear.

PMID- 29221932
TI  - Evaluation of Guidelines for Surgical Management of Urolithiasis.
AB  - PURPOSE: Many urological societies have provided evidence-based guidelines to
      help the urologist make therapeutic choices. However, the recommendations in
      these guidelines may be heterogeneous because they were developed using various
      methods. The objective of this study was to review key guidelines on the surgical
      management of urinary stones to provide practical guidance for clinical
      application. MATERIALS AND METHODS: Guidelines on urolithiasis from all
      international urological societies were searched through the society websites. A
      search on PubMed(r) and Medline(r) restricted to publications in English was also
      performed for guidelines published between January 1, 2010 and July 1, 2017. Only
      the latest versions of guidelines containing an evaluation of the level of
      evidence and the grade of recommendation were included in the final analysis. All
      recommendations on surgical stone management and recommended techniques for each
      surgical modality were included. The AGREE II (Appraisal of Guidelines for
      Research and Evaluation II) instrument was used to assess the quality of the
      included guidelines. RESULTS: Three international guidelines were included in
      analysis, including those of AUA (American Urological Association)/ES
      (Endourological Society), EAU (European Association of Urology) and SIU (Societe
      Internationale d'Urologie)/ICUD (International Consultation on Urological
      Diseases). We highlighted the heterogeneity in the level of evidence and the
      grade of recommendation which arose due to the different methods of evaluations
      that had been adopted. Despite this our review highlighted the considerable
      similarities among the guidelines. In certain specific situations for which no
      good evidence was available the recommendations could only be based on expert
      opinion. CONCLUSIONS: An option to provide clear guidance to the urologist might
      be to combine these international guidelines into one to reduce confusion about
      the surgical management of urolithiasis.

PMID- 29221933
TI  - Intestinal Intraepithelial Lymphocytes: Sentinels of the Mucosal Barrier.
AB  - Intestinal intraepithelial lymphocytes (IELs) are a large and diverse population
      of lymphoid cells that reside between the intestinal epithelial cells (IECs) that
      form the intestinal mucosal barrier. Although IEL biology has traditionally
      focused on T cells, recent studies have identified several subsets of T cell
      receptor (TCR)-negative IELs with intriguing properties. New insight into the
      development, homeostasis, and functions of distinct IEL subsets has recently been
      provided. Additional studies have revealed intricate interactions between
      different IEL subsets, reciprocal interactions between IELs and IECs, and
      communication of IELs with immune cells that reside outside the intestinal
      epithelium. We review here sentinel functions of IELs in the maintenance of the
      mucosal barrier integrity, as well as how dysregulated IEL responses can
      contribute to pathology.

PMID- 29221934
TI  - Response to "Re. Management of Atherosclerotic Carotid and Vertebral Disease:
      2017 Clinical Practice Guidelines of the European Society for Vascular Surgery
      (ESVS)".

PMID- 29221935
TI  - Effects of intermolecular interactions on absorption intensities of the
      fundamental and the first, second, and third overtones of OH stretching
      vibrations of methanol and t-butanol-d9 in n-hexane studied by visible/near
      infrared/infrared spectroscopy.
AB  - Visible (Vis), near-infrared (NIR) and IR spectra in the 15,600-2500cm-1 region
      were measured for methanol, methanol-d3, and t-butanol-d9 in n-hexane to
      investigate effects of intermolecular interaction on absorption intensities of
      the fundamental and the first, second, and third overtones of their OH stretching
      vibrations. The relative area intensities of OH stretching bands of free and
      hydrogen-bonded species were plotted versus the vibrational quantum number using
      logarithm plots (V=1-4) for 0.5M methanol, 0.5M methanol-d3, and 0.5M t-butanol
      d9 in n-hexane. In the logarithm plots the relative intensities of free species
      yield a linear dependence irrespective of the solutes while those of hydrogen
      bonded species deviate significantly from the linearity. The observed results
      suggest that the modifications in dipole moment functions of the OH bond induced
      by the formation of the hydrogen bondings change transient dipole moment, leading
      to the deviations of the dependences of relative absorption intensities on the
      vibrational quantum number from the linearity.

PMID- 29221936
TI  - Volumetric measurement of hepatic tumors: Accuracy of manual contouring using CT
      with volumetric pathology as the reference method.
AB  - PURPOSE: The purpose of this study was to assess the accuracy of liver tumor
      volumetry by manual contouring on computed tomography (CT) compared to
      pathological tumor volume determined from surgical specimen that served as a
      reference method. PATIENTS AND METHOD: Thirty-eight patients with planned liver
      surgery and a total of 41 liver tumors were included. There were 24 men and 14
      women (mean age: 57 years; range: 32-85 years). Two readers calculated tumor
      volume by manual contouring on axial CT images. The reference tumor volume was
      calculated by manual contouring with dedicated software applied to the liver
      specimen slice. CT and pathology volumes were compared and the percentage of
      error (PE%) was calculated. Intraobserver and interobserver variabilities were
      calculated using Bland and Altman plots, and intraclass correlation coefficients
      (ICC). RESULTS: A strong correlation was found between CT tumor volumes and
      pathology tumor volumes (r=0.994; P<0.001 for both readers). The mean (+/-SD) and
      median (range) PE% were 19%+/-12% and 16% (1%, +42%) and 19%+/-15% and 17% (0%,
      +55%) for readers 1 and 2, respectively. Readers 1 and 2 significantly
      overestimated tumor volume (i.e., PE%>40%) in 3 (7%) and 2 (5%) tumors on CT,
      respectively. Tumor volume was not significantly underestimated in any of the
      patients (i.e. PE%>33%). Tumor size, CT attenuation, time between imaging and
      surgery, contours and margin definition did not influence the results of PE%
      values (all P values>0.05 for both readers). The bias and limits of agreement
      between the two readers were +4.6% and (-24%, +33%) with an ICC of 0.997.
      CONCLUSION: There was a strong correlation between tumor volume measured on CT
      and that assessed with surgical specimen. Tumor size, visibility of contours and
      tumor margins and the time between CT and surgery did not influence the results.

PMID- 29221937
TI  - Recurrent miscarriage is associated with increased ghrelin mRNA expression in the
      endometrium- a case-control study.
AB  - Ghrelin has been found to be expressed in the human endometrium. Emerging
      evidence links ghrelin and its receptor with the reproductive system. Certain
      associations between ghrelin and angiogenesis have also been established. The aim
      of this small case-control study was to quantify and compare the expression of
      mRNA encoding ghrelin, ghrelin receptor (GHS-R), vascular endothelial growth
      factor A (VEGF A) and its receptors (VEGFR1-3) in the endometrium of women with
      recurrent miscarriage compared to parous controls. Correlations between the
      expression of particular genes were also investigated. Endometrial samples were
      obtained during the secretory phase of the menstrual cycle from 15 women with a
      history of recurrent miscarriage (first trimester pregnancy loss without a known
      cause) and 10 healthy parous controls. Ghrelin, GHS-R, VEGF A and VEGFR1-3 mRNA
      expression was analyzed by quantitative RT-PCR. The expression of mRNA for
      ghrelin and VEGF A was significantly higher in the study group than the control
      group. In the control group, the expression of ghrelin mRNA was positively
      correlated with the expression of VEGF A and VEGFR1 mRNA. In the study group, no
      such associations were observed. These results show that the expression of mRNA
      for ghrelin and VEGF A may be increased in the endometrium of women with
      recurrent miscarriage thus suggesting that ghrelin may play a role in the
      pathogenesis of recurrent miscarriage.

PMID- 29221938
TI  - Are women with obesity and infertility willing to attempt weight loss prior to
      fertility treatment?
AB  - OBJECTIVE: To assess attitudes towards weight loss interventions in patients
      seeking infertility treatment. METHODS: We evaluated prior weight loss
      experiences, attitudes towards future interventions by body mass index (BMI), and
      willingness to delay fertility treatment for weight loss interventions stratified
      by BMI using logistic regression amongst women <=45years old with infertility
      over three months or recurrent pregnancy loss. RESULTS: The average age of our
      convenience sample of respondents (148 of 794 eligible women, 19%) was 34.5 years
      old, with a mean BMI of 26.7+/-7.4kg/m2, including 37 with a BMI >30kg/m2 (25%).
      Most women had attempted conception over 1year. The majority of women with
      overweight or obesity were attempting weight loss at the time of survey
      completion (69%). While 47% of these women reported interest in a supervised
      medical weight loss program, 92% of overweight women and 84% of women with
      obesity were not willing to delay fertility treatment more than 3 months to
      attempt weight loss. CONCLUSION: Most women with obesity and infertility in our
      population are unwilling to postpone fertility treatment for weight loss
      interventions.

PMID- 29221939
TI  - Obesity and contraceptive use among women 20-44years of age in the United States:
      results from the 2011-15 National Survey of Family Growth (NSFG).
AB  - OBJECTIVE: Obesity has increased dramatically in the United States in recent
      decades. Our objective was to explore associations of contraceptive choices of US
      women, aged 20-44years, with body mass index (BMI) and relevant covariates. STUDY
      DESIGN: Data are based on interviews with a national sample of 11,300 women in
      the 2011-2015 National Survey of Family Growth. We analyzed women ages 20-44 at
      risk of unintended pregnancy. The primary dependent variable was BMI category.
      Covariates analyzed included age, parity, race/ethnicity, marital status, self
      reported health and education. Data were analyzed via cross-tabulation and
      logistic regression. We determined unadjusted and adjusted odds ratios for three
      categories of contraceptive method: female sterilization, intrauterine device
      (IUD) and hormonal contraception. RESULTS: Obese women have higher odds of female
      sterilization (BMI 30.0-34.9 kg/m2: adjusted odds ratio (aOR)=1.96, 95%
      confidence interval (CI) 1.45-2.66; BMI 35.0 kg/m2 and higher: aOR=1.56, 95% CI
      1.13-2.14) compared to women with normal BMI. Odds of IUD use are significantly
      higher among women with BMI >35 kg/m2 (aOR=1.64, 95% CI 1.20-2.25). Odds of
      hormonal contraceptive use are correspondingly reduced (aOR=0.78, 95% CI 0.62
      0.98) for women in the highest BMI category. CONCLUSIONS: Contraceptive use
      varies by BMI category even after adjusting for usual correlates of use.
      Differences in contraceptive use by BMI category have implications for
      contraceptive counseling and provision. IMPLICATIONS: Findings that obese women
      are more likely to rely on female sterilization raise questions about how weight
      concerns and obesity affect contraceptive decision making. Future research could
      explore associations between obesity and contraceptive use in adolescent women.

PMID- 29221940
TI  - Pioglitazone attenuates aging-related disorders in aged apolipoprotein E
      deficient mice.
AB  - Pioglitazone (Piog) activates peroxisome proliferator activated receptor-gamma
      (PPARgamma) and is widely used in clinic for the treatment of diabetes mellitus.
      PPARgamma in various tissues has the essential regulatory role of multiple
      metabolic function, suggest that PPARgamma signaling may contribute to aging
      processes. However, little is known about the consequences of Piog on aging in
      aged animal models. We used apolipoprotein E deficient (apoE-/-) mice model to
      evaluate the effects of Piog on aging-related disorders. Our results showed that
      long-term and low-dose Piog treatment significantly reduced aortic
      atherosclerosis, aging-related renal glomerulosclerosis and interstitial
      fibrosis, and hepatic steatosis, while improved the dermis in skin atrophy,
      compared to the control group. These morphological alterations were linked to the
      role of Piog, including regulation of plasma cholesterol and triglycerides (TG)
      levels, increased antioxidant superoxide dismutase (SOD) activity and decreased
      myeloperoxidase (MPO) activity. Moreover, accompanied with up-regulation of
      PPARgamma expression, Piog had obviously increased the mRNA levels of anti-aging
      genes Sirtuin1 and Klotho, decreased the p53 protein level, and altered the
      expression of several genes involving cholesterol excretion, TG biosynthesis and
      inflammation in the liver. In conclusion, Piog treatment is effective to modulate
      the oxidative and inflammatory status, cell senescence, and lipid metabolism,
      contributing to attenuate several aging-related disorders in the aged apoE-/-
      mice, thereby maybe a promising protective therapy of aging and age-related
      diseases.

PMID- 29221941
TI  - Are Human Development Index dimensions associated with gait performance in older
      adults? A systematic review.
AB  - BACKGROUND: Because gait performance is a marker of organic integrity, and the
      Human Development Index (HDI) of a region impacts the organism globally, this
      paper aims to investigate possible associations between both HDI and HDI
      dimensions at individual level (i.e. education, income, or life expectancy) with
      gait performance in older adults. METHODS: Searches were conducted on EMBASE and
      PubMed databases. Eligible studies included community-dwelling population aged
      >=60years, analysis of at least one quantitative gait variable, observational
      studies, Human Development Index or its dimensions (i.e. education, income, or
      life expectancy). RESULTS: Thirty-five articles were included in this systematic
      review. No study directly used HDI as an independent variable, but all selected
      articles found relationships between gait performance and one or two HDI
      dimensions at individual-level in the same study. Gait speed was the most common
      dependent variable associated with all three HDI dimensions. Low education, poor
      income, and short life expectancy were associated with worse gait speed, in
      combination and/or independently. CONCLUSION: No studies were found using HDI as
      a main variable. Systematic evidence showed a strong relationship with all three
      HDI dimensions: education, income, and life expectancy, suggesting that social
      factors at individual level affect gait performance.

PMID- 29221942
TI  - Neurostimulant use is associated with improved survival in comatose patients
      after cardiac arrest regardless of electroencephalographic substrate.
AB  - AIM: Identify EEG patterns that predict or preclude favorable response in
      comatose post-arrest patients receiving neurostimulants. METHODS: We examined a
      retrospective cohort of consecutive electroencephalography (EEG)-monitored
      comatose post-arrest patients. We classified the last day of EEG recording before
      neurostimulant administration based on continuity (continuous/discontinuous),
      reactivity (yes/no) and malignant patterns (periodic discharges, suppression
      burst, myoclonic status epilepticus or seizures; yes/no). In subjects who did not
      receive neurostimulants, we examined the last 24h of available recording. For our
      primary analysis, we used logistic regression to identify EEG predictors of
      favorable response to treatment (awakening). RESULTS: In 585 subjects, mean (SD)
      age was 57 (17) years and 227 (39%) were female. Forty-seven patients (8%)
      received a neurostimulant. Neurostimulant administration independently predicted
      improved survival to hospital discharge in the overall cohort (adjusted odds
      ratio (aOR) 4.00, 95% CI 1.68-9.52) although functionally favorable survival did
      not differ. No EEG characteristic predicted favorable response to
      neurostimulants. In each subgroup of unfavorable EEG characteristics,
      neurostimulants were associated with increased survival to hospital discharge
      (discontinuous background: 44% vs 7%, P=0.004; non-reactive background: 56% vs
      6%, P<0.001; malignant patterns: 63% vs 5%, P<0.001). CONCLUSION: EEG patterns
      described as ominous after cardiac arrest did not preclude survival or awakening
      after neurostimulant administration. These data are limited by their
      observational nature and potential for selection bias, but suggest that EEG
      patterns alone should not affect consideration of neurostimulant use.

PMID- 29221943
TI  - Religious hospital policies on reproductive care: what do patients want to know?
AB  - BACKGROUND: Religious hospitals are a large and growing part of the American
      healthcare system. Patients who receive obstetric and other reproductive care in
      religious hospitals may face religiously-based restrictions on the treatment
      their doctor can provide. Little is known about patients' knowledge or
      preferences regarding religiously restricted reproductive healthcare.
      OBJECTIVE(S): We aimed to assess women's preferences for knowing a hospital's
      religion and religiously based restrictions before deciding where to seek care
      and the acceptability of a hospital denying miscarriage treatment options for
      religious reasons, with and without informing the patient that other options may
      be available. STUDY DESIGN: We conducted a national survey of women aged 18-45
      years. The sample was recruited from AmeriSpeak, a probability-based research
      panel of civilian noninstitutionalized adults. Of 2857 women invited to
      participate, 1430 completed surveys online or over the phone, for a survey
      response rate of 50.1%. All analyses adjusted for the complex sampling design and
      were weighted to generate estimates representative of the population of US adult
      reproductive-age women. We used chi2 tests and multivariable logistic regression
      to evaluate associations. RESULTS: One third of women aged 18-45 years (34.5%)
      believe it is somewhat or very important to know a hospital's religion when
      deciding where to get care, but 80.7% feel it is somewhat or very important to
      know about a hospital's religious restrictions on care. Being Catholic or
      attending religious services more frequently does not make one more or less
      likely to want this information. Compared with Protestant women who do not
      identify as born-again, women of other religious backgrounds are more likely to
      consider it important to know a hospital's religious affiliation. These include
      religious minority women (adjusted odds ratio, 2.17; 95% confidence interval,
      1.11-4.27), those who reported no religion/atheist/agnostic (adjusted odds ratio,
      2.27; 95% confidence interval, 1.19-4.34), and born-again Protestants (adjusted
      odds ratio, 2.38; 95% confidence interval, 1.32-4.28). Religious minority women
      (adjusted odds ratio, 2.36; 95% confidence interval, 1.01-5.51) and those who
      reported no religion/atheist/agnostic (adjusted odds ratio, 3.16; 95% confidence
      interval, 1.42-7.04) were more likely to want to know a hospital's restrictions
      on care. More than two thirds of women find it unacceptable for the hospital to
      restrict information and treatment options during miscarriage based on religion.
      Women who attended weekly religious services were significantly more likely to
      accept such restrictions (adjusted odds ratio, 3.13; 95% confidence interval,
      1.70-5.76) and to consider transfer to another site an acceptable solution
      (adjusted odds ratio, 3.22; 95% confidence interval, 1.69-6.12). The question,
      "When should a religious hospital be allowed to restrict care based on religion?"
      was asked, and 52.3% responded never; 16.6%, always; and 31.1%,"under some
      conditions. CONCLUSION: The vast majority of adult American women of reproductive
      age want information about a hospital's religious restrictions on care when
      deciding where to go for obstetrics/gynecology care. Growth in the US Catholic
      health care sector suggests an increasing need for transparency about these
      restrictions so that women can make informed decisions and, when needed, seek
      alternative providers.

PMID- 29221944
TI  - Living uterus donation and transplantation: experience of interest and screening
      in a single center in the United States.
AB  - BACKGROUND: Little is known about attitudes toward uterus donation and
      transplantation in society and the interest of the women the treatment is aimed
      to assist. OBJECTIVE: This study examined the interest of recipients and living
      donors in our uterus transplantation program; it describes the screening protocol
      we developed and the results of the screening and reports demographic data and
      characteristics of screened candidates. STUDY DESIGN: Initial screening and
      evaluation included physical examinations by a gynecologist and a transplant
      surgeon; psychological evaluation; imaging (x-ray, computed tomography,
      ultrasound); blood tests; immunological testing; viral, bacterial, and fungal
      testing; drug screen; hormonal testing; Papanicolau smear; urinalysis; and
      electrocardiogram. For selected recipients, the process also included in vitro
      fertilization. RESULTS: A total of 351 women contacted our department with
      interest in participating in uterus transplantation; 272 were potential
      recipients and 79 were potential donors. Among these women, 179 potential
      recipients and 62 potential donors continued the evaluation after the initial
      telephone screening. The mean age of the donor candidates was 40 years; all had
      completed their own family, and 80% were nondirected. Most recipient candidates
      (92%) had an anatomical lack of the uterus, and of these, 36% had a congenital
      malformation. The women with a congenital uterine absence were in general younger
      than the women in the group whose uterus had been removed (mean of 28 and 33
      years, respectively). In every step of the initial screening and evaluation
      process, there were donor and recipient candidates that chose not to continue the
      process. The reasons for self-withdrawal after expressing interest were not
      returning phone calls or e-mails (17 donors and 76 recipients); after initial
      phone screening, no longer interested (1 donor and 9 recipients); in step 1,
      health history questionnaire not returned after 1 reminder (10 donors and 9
      recipients); step 2, not right in their current life situation (2 donors and 2
      recipients), and in step 3, chose another way to achieve motherhood (1
      recipient). Most donor and recipient candidates (52% and 78%, respectively) could
      be screened out (because of self-withdrawal or transplant team's decision) during
      the noninvasive and cost-efficient initial screening. CONCLUSION: Our initial
      experience shows a great interest in participating in a trial of uterus
      transplantation by both potential recipients and donors. It is the first study to
      show interest in nondirected donation. A sufficient but thoughtful screening
      process of living donors and recipients is essential and should aim both to
      assure donor/recipient safety and to provide good quality grafts.

PMID- 29221946
TI  - [Facing a dilemma in elderly complex and vulnerable patients: to stop or not to
      stop prevention?]
AB  - OBJECTIVES: 1-To know the preventive prescription (statin, antiplatelet drugs,
      bisphosphonates, calcium and vitamin D and Vit B12) of elderly patients
      previously identified as a CCD (with a complex chronic disease) and ACD (with
      advanced chronic disease and lifetime expectancy of less than 12 months) who died
      during 2015. 2-To assess the correct indication of Proton Pump Inhibitors (PPI)
      to determine potentially avoidable medication. DESIGN: Retrospective
      observational study. LOCATION: Four Primary Health Centres, Castellar del Valles
      (Barcelona). PARTICIPANTS: 128 patients, 70 ACD and 58 PCC. MAIN MEASUREMENTS:
      Number of drugs at the time of death from the 6 selected group, deprescription (6
      months prior to death due to advanced chronic disease), primary or secondary
      prevention and inappropriate prescription of PPI. RESULTS: Average age of 85'3
      years (10,3). 40% took an antiplatelet drug, avoidable in 60% of the ACD, since
      they did not present any previous cardiovascular episode. 20% of the patients
      took statins, in which 48% of the cases were primary prevention. The PPI
      prescription was 67% with inadequate indication for use in 49% of these cases.
      20% took calcium / Vitamin D and 1,6% of the ACD a bisphosphonate. There was a
      16% deprescription. CONCLUSIONS: A high percentage of our patients with advanced
      chronic disease and short life expectancy still continue to take preventive and
      avoidable treatments, potentially dangerous due to their side effects. There is a
      need to reflect on what we do with these vulnerable patients.

PMID- 29221945
TI  - The relationship of Physical performance and Osteoporosis prevention with vitamin
      D in older African Americans (PODA).
AB  - RATIONALE: Vitamin D deficiency is associated with bone loss, poor muscle
      strength, falls and fracture. This information in older African Americans (AAs)
      is sparse. OBJECTIVE: The study of the relationship of Physical performance,
      Osteoporosis prevention with vitamin D in older African Americans (PODA) is a
      randomized, double-blind, placebo-controlled 3-year trial examining the effect of
      vitamin D on bone loss and physical performance in older AA women. METHODS: 260
      healthy AA women aged >60years were assigned to receive placebo or vitamin D3.
      Initial vitamin D3 dose was determined by the baseline serum 25OHD level, and
      adjusted further to maintain serum 25OHD between 30 and 69ng/ml. Subjects with
      baseline 25OHD levels <=8ng/ml or >=26ng/ml were excluded. Objective measures of
      neuromuscular strength [Short Physical Performance Battery (SPPB), grip strength
      and 6-minute walking distance (6MWD)] and bone mineral density (BMD) were
      obtained. RESULTS: SPPB gait speed, grip strength and 6MWD showed a significant
      positive correlation with free 25OHD. 1pg/ml increase in free 25OHD predicted a
      32% increase in the odds of having higher gait speed and a 1.42lb. increase in
      grip strength. No significant differences in BMI, BMD, muscle mass, grip
      strength, serum total 25OHD and free 25OHD were observed between groups. None of
      the measures of physical performance showed an association with baseline serum
      25OHD. CONCLUSIONS: This is the first study to show an association between free
      25OHD and physical performance. These findings indicate a positive relationship
      of free 25OHD with gait speed and grip strength in older AA women. Further
      studies are needed to understand the role of free 25OHD.

PMID- 29221947
TI  - [The impact of patient identification on an integrated program of palliative care
      in Basque Country].
AB  - OBJECTIVE: Evaluate the process and the economic impact of an integrated
      palliative care program. DESIGN: Comparative cross-sectional study. LOCATION:
      Integrated Healthcare Organizations of Alto Deba and Goierri Alto-Urola, Basque
      Country. PARTICIPANTS: Patients dead due to oncologic and non-oncologic causes in
      2012 (control group) and 2015 (intervention group) liable to need palliative care
      according to McNamara criteria. INTERVENTIONS: Identification as palliative
      patients in primary care, use of common clinical pathways in primary and
      secondary care and arrange training courses for health professionals. MAIN
      MEASURES: Change in the resource use profile of patients in their last 3 months.
      Propensity score by genetic matching method was used to avoid non-randomization
      bias. The groups were compared by univariate analysis and the relationships
      between variables were analysed by logistic regressions and generalized linear
      models. RESULTS: One thousand and twenty-three patients were identified in 2012
      and 1,142 patients in 2015. In 2015 doubled the probability of being identify as
      palliative patient in deaths due to oncologic (19-33%) and non-oncologic causes
      (7-16%). Prescriptions of opiates rise (25-68%) and deaths in hospital remained
      stable. Contacts per patient with primary care and home hospitalization
      increased, while contacts with hospital admissions decreased. Cost per patient
      rise 26%. CONCLUSIONS: The integrated palliative care model increased the
      identification of the target population. Relationships between variables showed
      that the identification had a positive impact on prescription of opiates, death
      outside the hospital and extension to non-oncologic diseases. Although the
      identification decreased admissions in hospital, costs per patient had a slight
      increase due to home hospitalizations.

PMID- 29221948
TI  - CNB-001, a synthetic pyrazole derivative of curcumin, suppresses
      lipopolysaccharide-induced nitric oxide production through the inhibition of NF
      kappaB and p38 MAPK pathways in microglia.
AB  - CNB-001, a pyrazole derivative of curcumin, has been found to exert
      neuroprotective and memory-enhancing effects that may be effective for the
      treatment of Alzheimer's disease. Since aberrant activation of microglia is
      involved in the pathogenesis of Alzheimer's disease, the present study was
      undertaken to investigate the effect of CNB-001 on microglia-mediated
      inflammatory responses. In primary cultured rat microglia, CNB-001 (1-10uM)
      suppressed the lipopolysaccharide (LPS)-induced nitric oxide (NO) production and
      expression of inducible NO synthase (iNOS), and the potency of CNB-001 was
      stronger than curcumin. CNB-001 also suppressed the LPS-induced nuclear
      translocation of nuclear factor kappaB (NF-kappaB), which is essential for the
      expression of iNOS. LPS treatment promoted phosphorylation of extracellular
      signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen
      activated protein kinase (MAPK). CNB-001 significantly suppressed the LPS-induced
      phosphorylation of p38 MAPK, but not ERK and JNK. The suppressive effect of CNB
      001 on NO production was mimicked by blockade of the p38 MAPK signaling pathway
      with SB203580. These results suggest that CNB-001 exerts anti-inflammatory
      effects through inhibition of NF-kappaB and p38 MAPK pathways in microglia.

PMID- 29221949
TI  - Anti-cancer activity of a new dihydropyridine derivative, VdiE-2N, in head and
      neck squamous cell carcinoma.
AB  - This study aims to examine the effects of a new 1,4-dihydropyridine derivative,
      VdiE-2N, on cell signaling pathways and mitochondrial events in head and neck
      squamous cell carcinoma (HNSCC) cells, and on a mice model of xenograft tumor
      growth/cell proliferation. Four HNSCC cell lines (HN13, HN12, HN6, and CAL27),
      HEK293 cells (human embryonic kidney 293 cells), and human oral healthy mucosa
      fibroblasts (OHMF) were used for in vitro assessment of cell viability (resazurin
      assay) and invasion capacity (modified Boyden chamber assay), and mitochondrial
      membrane potential (JC-1 fluorescence assay), morphology (transmission electron
      microscopy), and number of mitochondria (MitoTracker(r) imaging). SET and pDRP1
      proteins were analyzed by immunofluorescence, and proteins involved in cell
      death/survival pathways were analyzed by Western blotting. HN12 xenograft tumors
      were established in the flank of Balb/c nude mice, and their characteristics and
      sensitivity to VdiE-2N were determined by immunohistochemistry and histology.
      VdiE-2N decreased cell viability in HNSCC cells (IC50 = 9.56 and 22.45uM for HN13
      and HN12 cells, respectively) more strongly than it decreased cell viability in
      OHMF and HEK293 cells (IC50 = 32.90 and > 50uM, respectively). In HN13 cells,
      VdiE-2N dissipated mitochondrial membrane potential and altered the mitochondria
      size, shape, and number in a concentration-dependent manner, as well as it
      induced apoptosis and reduced their invasion capacity. Treatment of mice bearing
      xenograft tumors with VdiE-2N significantly diminished proliferation of cancer
      cells. Therefore, VdiE-2N induces HNSCC cell death in vitro through mitochondria
      mediated apoptotic pathways and dampens tumor growth in vivo, thus supporting a
      potential anti-cancer effect.

PMID- 29221950
TI  - DHA supplementation prevent the progression of NASH via GPR120 signaling.
AB  - Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases
      involving chronic accumulation of fat and inflammation, often leading to advanced
      fibrosis, cirrhosis and carcinoma. However, the pathological mechanism for this
      is unknown. GPR120/FFAR4 has been recognized as a functional fatty acid receptor
      and an attractive therapeutic target for metabolic diseases. In this study, we
      investigated the involvement of GPR120/FFAR4 in the pathogenesis of NASH. Mice
      fed with a 0.1% methionine and choline deficient high-fat (CDAHF) diet showed a
      significant increase in plasma aspartate transaminase and alanine transaminase
      levels, fatty deposition, inflammatory cell infiltration, and mild fibrosis.
      Docosahexaenoic acid (DHA, GPR120/FFAR4 agonist) suppressed the inflammatory
      cytokines in the liver tissues and prevented fibrosis in the wild type (WT) mice
      fed CDAHF diet, but not GPR120/FFAR4 deficient (GPR120KO) mice. GPR120KO mice fed
      CDAHF diet showed increment of the number of crown like structures and the
      immunoreactivity for F4/80 positive cells, and increased TNF-alpha mRNA in the
      liver compared to WT mice fed CDAHF diet. GPR120 KO mice fed CDAHF diet showed
      more severe liver inflammation than that of WT mice fed CDAHF diet, but not
      fibrosis. Our findings suggest that DHA supplementation could be prevented the
      development of NASH via GPR120/FFAR4 signaling. Furthermore, decrease of
      GPR120/FFAR4 signaling could be facilitated an inflammatory response in the
      process of NASH progression.

PMID- 29221951
TI  - Role of drugs in the prevention and amelioration of radiation induced toxic
      effects.
AB  - As the use of radiation technology for nuclear warfare or for the benefits of
      mankind (e.g. in radiotherapy or radio-diagnosis) is increasing tremendously, the
      risk of associated side effects is becoming a cause of concern. These effects,
      ranging from nausea/vomiting to death, may result from accidental or deliberate
      exposure and begin in seconds. Through this review paper, efforts have been done
      to critically review different compounds which have been investigated as
      radioprotectors and radiation mitigators. Radioprotectors are compounds which are
      administered just before or at the time of irradiation so as to minimize the
      radiation induced damage to normal tissues. And radiation mitigators are the
      compounds which can even minimize or ameliorate post irradiaion-toxicity provided
      they are administered before the onset of toxic symptoms. A variety of agents
      have been investigated for their preventive and ameliorative potential against
      radiation induced toxic effects. This review article has focused on various
      aspects of the promising representative agents belonging to different classes of
      radioprotectors and mitigators. Many compounds have shown promising results, but
      till date only amifostine and palifermin are clinically approved by FDA. To fill
      this void in pharmacological armamentarium, focus should be shifted towards novel
      approaches.

PMID- 29221952
TI  - Danshensu prevents hypoxic pulmonary hypertension in rats by inhibiting the
      proliferation of pulmonary artery smooth muscle cells via TGF-beta-smad3
      associated pathway.
AB  - Hypoxic pulmonary hypertension is characterized by the remodeling of pulmonary
      artery. Previously we showed that tanshinone IIA, one lipid-soluble component
      from the Chinese herb Danshen, ameliorated hypoxic pulmonary hypertension by
      inhibiting pulmonary artery remodeling. Here we explored the effects of
      danshensu, one water-soluble component of Danshen, on hypoxic pulmonary
      hypertension and its mechanism. Rats were exposed to hypobaric hypoxia for 4
      weeks to develop hypoxic pulmonary hypertension along with administration of
      danshensu. Hemodynamics and pulmonary arterial remodeling index were measured.
      The effects of danshensu on the proliferation of primary pulmonary artery smooth
      muscle cells and transforming growth factor-beta-smad3 pathway were assessed in
      vitro. Danshensu significantly decreased the right ventricle systolic pressure,
      the right ventricle hypertrophy and pulmonary vascular remodeling index in
      hypoxic pulmonary hypertension rats. Danshensu also reduced the increased
      expression of transforming growth factor-beta and phosphorylation of smad3 in
      pulmonary arteries in hypoxic pulmonary hypertension rats. In vitro, danshensu
      inhibited the hypoxia- or transforming growth factor-beta-induced proliferation
      of primary pulmonary artery smooth muscle cells. Moreover, danshensu decreased
      the hypoxia-induced expression and secretion of transforming growth factor in
      primary pulmonary adventitial fibroblasts and NR8383 cell line, inhibited the
      hypoxia or transforming growth factor-beta-induced phosphorylation of smad3 in
      rat primary pulmonary artery smooth muscle cells. These results demonstrate that
      danshensu ameliorates hypoxic pulmonary hypertension in rats by inhibiting the
      hypoxia-induced proliferation of pulmonary artery smooth muscle cells, and the
      inhibition effects is associated with transforming growth factor-beta-smad3
      pathway. Therefore danshensu may be a potential treatment for hypoxic pulmonary
      hypertension.

PMID- 29221953
TI  - Antitumor action of 3-bromopyruvate implicates reorganized tumor growth
      regulatory components of tumor milieu, cell cycle arrest and induction of
      mitochondria-dependent tumor cell death.
AB  - Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a
      potent antitumor action against a wide range of malignancies. However, the effect
      of 3-BP on progression of the tumors of thymic origin remains unexplored.
      Although, constituents of tumor microenvironment (TME) plays a pivotal role in
      regulation of tumor progression, it remains unclear if 3-BP can alter the
      composition of the crucial tumor growth regulatory components of the external
      surrounding of tumor cells. Thus, the present investigation attempts to
      understand the effect of 3-BP administration to a host bearing a progressively
      growing tumor of thymic origin on tumor growth regulatory soluble, cellular and
      biophysical components of tumor milieu vis-a-vis understanding its association
      with tumor progression, accompanying cell cycle events and mode of cell death.
      Further, the expression of cell survival regulatory molecules and hemodynamic
      characteristics of the tumor milieu were analysed to decipher mechanisms
      underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing
      hosts retarded tumor progression accompanied by induction of tumor cell death,
      cell cycle arrest, declined metabolism, inhibited mitochondrial membrane
      potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3
      BP reconstituted the external milieu, in concurrence with deregulated glucose and
      pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T
      lymphocytes. Further, 3-BP administration altered the expression of key
      regulatory molecules involved in glucose uptake, intracellular pH and tumor cell
      survival. The outcomes of this study will help in optimizing the therapeutic
      application of 3-BP by targeting crucial tumor growth regulatory components of
      tumor milieu.

PMID- 29221954
TI  - Total particulate matter from cigarette smoke disrupts vascular development in
      zebrafish brain (Danio rerio).
AB  - Several studies have demonstrated zebrafish as a useful high-throughput in vivo
      model to study the effects of cigarette smoke on early development. It has been
      shown previously that exposure of zebrafish to cigarette smoke total particulate
      matter (TPM) leads to several adverse physiological aberrations, including heart
      deformities and improper angiogenesis. Consequently, this study investigated the
      effects of TPM on cardiovascular development in zebrafish that were exposed to
      increasing concentrations of TPM based upon nicotine content from 6h post
      fertilization (hpf) up to 72hpf. We show that TPM exposure in wild-type embryos
      led to a dose-dependent increase in fluorescence, especially in the yolk and head
      regions, suggesting bioaccumulation of cyclic compounds in TPM, such as
      polycyclic aromatic hydrocarbons (PAHs). Similarly, the incidence of cranial
      hemorrhage, pericardial edema, and string heart was increased with TPM exposure
      in a dose-dependent manner. Additionally, TPM exposure in transgenic (Flk1:eGFP)
      zebrafish showed a decrease in vascular abundance in the brain, but the
      transcript abundance of key angiogenic genes Tie-2, Angpt1, Notch3, and Flk1
      remained largely unchanged and that of Vegf actually increased with TPM. The
      study also investigated aspects of a proposed crosstalk between the activation of
      the aryl hydrocarbon receptor (AhR) pathway and subsequent inhibition of the Wnt
      signaling pathway, resulting in cardiac malformations. In an effort to reduce the
      occurrence of cardiovascular malformations, embryos/larvae were co-treated with
      CHIR99021 (CHIR), which should promote Wnt signaling. However, co-treatment with
      CHIR did not significantly affect the TPM-induced cardiovascular toxicity.
      Overall, results from this study demonstrate that exposure to TPM leads to
      several cardiovascular deformities and disrupted vascular development in the
      brain, and that these effects are associated with downregulation of Wnt
      signaling.

PMID- 29221955
TI  - Comparison of external and internal implant-abutment connections for implant
      supported prostheses. A systematic review and meta-analysis.
AB  - OBJECTIVE: The systematic review and meta-analysis aimed to answer the PICO
      question: "Do patients that received external connection implants show similar
      marginal bone loss, implant survival and complication rates as internal
      connection implants?". DATA: Meta-analyses of marginal bone loss, survival rates
      of implants and complications rates were performed for the included studies.
      Study eligibility criteria included (1) randomized controlled trials (RCTs)
      and/or prospective, (2) studies with at least 10 patients, (3) direct comparison
      between connection types and (4) publications in English language. The Cochrane
      risk of bias tool was used to assess the quality and risk of bias in RCTs, while
      Newcastle-Ottawa scale was used for non-RCTs. SOURCE: A comprehensive search
      strategy was designed to identify published studies on PubMed/MEDLINE, Scopus,
      and The Cochrane Library databases up to October 2017. STUDY SELECTION: The
      search identified 661 references. Eleven studies (seven RCTs and four prospective
      studies) were included, with a total of 530 patients (mean age, 53.93 years), who
      had received a total of 1089 implants (461 external-connection and 628 internal
      connection implants). The internal-connection implants exhibited lower marginal
      bone loss than external-connection implants (P<0.00001; Mean Difference (MD):
      0.44mm; 95% Confidence interval (CI): 0.26-0.63mm). No significant difference was
      observed in implant survival (P=0.65; Risk Ratio (RR): 0.83; 95% CI: 0.38-1.84),
      and complication rates (P=0.43; RR: 1.15; 95% CI: 0.81-1.65). CONCLUSION:
      Internal connections had lower marginal bone loss when compared to external
      connections. However, the implant-abutment connection had no influence on the
      implant's survival and complication rates. Based on the GRADE approach the
      evidence was classified as very low to moderate due to the study design,
      inconsistency, and publication bias. Thus, future research is highly encouraged.
      CLINICAL SIGNIFICANCE: Internal connection implants should be preferred over
      external connection implants, especially when different risk factors that may
      contribute to increased marginal bone loss are present.

PMID- 29221956
TI  - Global burden of molar incisor hypomineralization.
AB  - OBJECTIVES: We aimed to systematically review and meta-analyze the global, super
      regional, regional and national prevalence of molar-incisor-hypomineralization
      (MIH) and to determine the numbers of prevalent and incident cases on different
      spatial scales. The review was registered (PROSPERO CRD42017063842). SOURCES:
      Five electronic databases (Medline, EMBASE, LILACS, Web of Science, Google
      Scholar) were searched systematically. STUDY SELECTION: Observational studies on
      the prevalence of MIH were included and the prevalence on different spatial
      scales (global, super-regional, regional, national) synthesized using random
      effects meta-analyses. The prevalence was then regressed on a large set of
      methodological, socioeconomic and environmental variables to estimate the global
      burden (incident and prevalent cases) of MIH. DATA: Of 2239 identified studies,
      99 studies on 113,144 participants from 43 countries were included. The meta
      analysis yielded a mean (95% CI) prevalence of 13.1% (11.8-14.5%), with
      significant differences between super-regions, regions and countries. The number
      of prevalent cases in 2015 was estimated at 878 (791-971) million people, while
      the number of incident cases in 2016 was 17.5 (15.8-19.4) million. Of these,
      27.4% (23.5-31.7%) (in mean, 240 million prevalent and 4.8 million incident
      cases, respectively) were or will be in need of therapy due to pain,
      hypersensitivity or posteruptive breakdown. Heavily populated countries
      contribute significantly to the burden of prevalent cases, while growing
      countries like India, but also Pakistan or Indonesia rank first with respect to
      the number of incident cases. CONCLUSIONS: MIH is highly prevalent across the
      globe. Certain (mainly low- and middle income) countries shoulder the majority of
      this burden. Clinical significance The consistently high prevalence and the large
      proportion of cases in need of care should be considered by both clinicians in
      their daily practice and healthcare planners and policy makers.

PMID- 29221957
TI  - Endovascular repair of complex Juxtarenal aortic aneurysm using a combined
      fenestrated endograft and chimney technique.
AB  - Chimney EVAR (CHEVAR) and Fenestrated EVAR (FEVAR) are two options for management
      of very complex abdominal aortic aneurysm (AAA). While some anatomical factors
      may favor one strategy over the other, there are some cases where the anatomical
      challenges may require using a hybrid approach. We are reporting the case of an
      84-year-old male with a 6.8*5.7cm infrarenal abdominal aortic aneurysm that
      arises immediately below the level of the renal arteries and extends down to just
      above the iliac bifurcation with occluded celiac and inferior mesenteric arteries
      and severe bilateral renal artery stenosis with caudally oriented right renal and
      cranially oriented left renal artery. This case shows that a combined strategy
      with fenestrated graft and Chimney stenting is feasible for aortic aneurysm
      repair and may offer a reasonable option for patients with very complex aortic
      anatomy.

PMID- 29221958
TI  - A comparison of the ultrathin Orsiro Hybrid sirolimus-eluting stent with
      contemporary drug-eluting stents: A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Recent studies suggest the Orsiro sirolimus-eluting stent (O-SES),
      which has ultrathin struts with a biodegradable sirolimus-eluting polymer
      coating, performed better than contemporary drug-eluting stents (DES). We
      performed a meta-analysis to compare clinical outcomes for all randomized
      controlled trials (RCTs) of O-SES vs contemporary DES. METHODS/MATERIALS: PubMed,
      Cochrane CENTRAL, and meeting abstracts were searched for all RCTs comparing O
      SES with contemporary DES. Pooled estimates of longest available clinical
      outcomes at a minimum of one-year follow-up, presented as odds ratios (OR) [95%
      confidence intervals], were generated with random-effect models. RESULTS: We
      included 8 RCTs with a total of 11,176 patients (5444 O-SES and 5732 contemporary
      DES [3537 EES, 1295 ZES, and 1264 BP-BES) with a mean age of 65+/-11, 74% were
      male, 40% underwent PCI for stable angina, and 56% for ACS. We assessed outcomes
      comparing O-SES vs. everolimus-eluting stents, vs. permanent-polymer DES, and vs.
      all DES including biodegradable-polymer DES. Orsiro performed comparably in all
      categories with a trend toward a reduction in myocardial infarction (0.83 [0.68,
      1.02], p=0.07) and stent thrombosis (0.75 [0.54, 1.04], p=0.08). CONCLUSION:
      Overall, the Orsiro SES had similar clinical outcomes to contemporary DES with a
      trend toward reduction in myocardial infarction and stent thrombosis.

PMID- 29221959
TI  - Robotically-assisted percutaneous coronary intervention: Reasons for partial
      manual assistance or manual conversion.
AB  - BACKGROUND: Robotically-assisted percutaneous coronary intervention (R-PCI) is
      feasible for simple coronary lesions. OBJECTIVES: To determine the frequency and
      reasons for partial manual assistance or manual conversion during R-PCI in
      clinical practice. METHODS: The CorPath 200 System (Corindus, Waltham, MA)
      enables the operator to sit in a radiation-shielded cockpit and remotely control
      intracoronary devices including guidewires, balloons, and stents. Consecutive R
      PCI procedures performed over 18months were analyzed to identify reasons for
      planned or unplanned manual assistance or manual conversion, and categorized as
      due to 1) adverse event; 2) technical limitation of the robotic platform; or 3)
      limited guide catheter/wire support. RESULTS: During the study period, 108 R-PCI
      procedures (68.1+/-11.0years, 77.8% men, 69.4% elective PCI, 78.3% type B2/C
      lesions, and 50.3% left anterior descending/left main target lesion segment) were
      performed. High robotic technical success (91.7%) and clinical procedural success
      (99.1%) were achieved. Twenty procedures (18.5%) required either planned partial
      manual assistance (3.7%), unplanned partial manual assistance (7.4%), or manual
      conversion (7.4%). Among these procedures, manual assistance/conversion was
      required in 3 procedures for an adverse event (15%), 8 for technical limitation
      of the robotic platform (40%), and 9 for guide catheter/wire support issues
      (45%). CONCLUSIONS: High clinical success with R-PCI for a complex lesion cohort
      is possible with only occasional partial manual assistance or manual conversion.
      The majority of procedures requiring manual assistance/conversion were due to
      limited guide catheter/wire support or robotic platform limitations, rather than
      occurrence of adverse events.

PMID- 29221960
TI  - When everything else fails: High-pressure balloon for undilatable lesions.
AB  - Heavily calcified lesions are encountered with increasing frequency during
      percutaneous coronary interventions (PCI). This poses a significant problem as it
      often leads to suboptimal stent expansion, which in turn is a major cause for
      stent restenosis and thrombosis. Various technologies have been developed to
      tackle this. The high-pressure balloon (OPN) seems to be a promising adjunct in
      treating undilatable lesions. In this concise mini review we highlight the use of
      HPB and we present the current status of technology implemented in complex PCI
      cases.

PMID- 29221961
TI  - Prevalence of high on-treatment (aspirin and clopidogrel) platelet reactivity in
      patients with critical limb ischemia.
AB  - OBJECTIVES: The goal of this study is to establish the prevalence of high on
      treatment platelet reactivity to aspirin (HPRA) and clopidogrel (HPRC) in
      patients with critical limb ischemia (CLI). BACKGROUND: CLI is associated with an
      increased risk of death and cardiovascular events. Unlike other patient
      populations with atherosclerotic cardiovascular disease, previous studies failed
      to demonstrate a benefit of antiplatelet therapy in patients with CLI. METHODS:
      From June 2014 to November 2016, we performed platelet reactivity studies for
      P2Y12 and thromboxane A2 (TXA2) inhibition in 100 CLI patients receiving daily
      treatment with aspirin and clopidogrel. P2Y12 inhibition was measured by two
      assays: vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 assays.
      HPRC was defined as VerifyNow P2Y12 reactive units (PRU) >208 and VASP-platelet
      reactivity index (VASP-PRI) >50%. TXA2 inhibition was measured with the VerifyNow
      aspirin test and HPRA was defined as aspirin reaction units (ARU) >550. RESULTS:
      Mean age was 67+/-11 years, 50% were male, 80% had diabetes mellitus, and 26% had
      chronic renal insufficiency. Thirty-three percent of patients had a PRU >208 and
      46% a VASP-PRI >50%. HPRC was present in 26% of patients based on the criteria of
      both a PRU >208 and VASP-PRI >50%. HPRA was present in 25% of patients. The
      overall prevalence of HPR to ASA or clopidogrel was 35% and HPR to both drugs was
      present in 8% of patients. Clinical characteristics were similar between groups.
      CONCLUSIONS: HPR to aspirin or clopidogrel is highly prevalent in patients with
      CLI. Nearly one in ten patients with CLI is a hyporesponder to both aspirin and
      clopidogrel.

PMID- 29221964
TI  - Inflammatory hepatic adenomas: Characterization with hepatobiliary MRI contrast
      agents.
AB  - PURPOSE: To characterize the MRI appearance of inflammatory hepatic adenomas
      using hepatobiliary contrast agents. MATERIALS AND METHODS: MRI was performed
      using hepatobiliary contrast agents (3 with gadobenate dimeglumine and 24 with
      gadoxetic acid) in 27 patients with immunohistochemistry-confirmed diagnosis of
      inflammatory hepatic adenoma. The appearance of the lesions on T2 and diffusion
      weighted images, pre-gadolinium T1-weighted images, dynamic post-gadolinium
      images, and hepatobiliary phase images was assessed. RESULTS: Seven lesions (26%)
      showed predominant hyperenhancement on hepatobiliary phase images in comparison
      with adjacent hepatic parenchyma: 1 lesion showed diffuse, mildly heterogeneous
      hyperenhancement, and the remaining 6 lesions showed peripheral hyperenhancement
      and central hypoenhancement. Twenty lesions (74%) were predominantly
      hypoenhancing compared to adjacent liver on hepatobiliary phase images. Nine
      lesions showed a pattern of peripheral hyperenhancement and central
      hypoenhancement on hepatobiliary phase images; in 6 of these lesions a majority
      of the mass appeared hyperenhancing, while the remaining 3 lesions showed
      predominant hypoenhancement. CONCLUSIONS: This investigation shows that a
      significant percentage of inflammatory hepatic adenomas appear isointense or
      hyperintense in comparison to adjacent normal liver on hepatobiliary phase
      images, and therefore this feature should not be used to distinguish hepatic
      adenomas from focal nodular hyperplasia without additional supporting evidence.

PMID- 29221962
TI  - Drug delivery and tissue engineering to promote wound healing in the
      immunocompromised host: Current challenges and future directions.
AB  - As regenerative medicine matures as a field, more promising technologies are
      being translated from the benchtop to the clinic. However, many of these
      strategies are designed with otherwise healthy hosts in mind and validated in
      animal models without other co-morbidities. In reality, many of the patient
      populations benefiting from drug delivery and tissue engineering-based devices to
      enhance wound healing also have significant underlying immunodeficiency.
      Specifically, patients suffering from diabetes, malignancy, human
      immunodeficiency virus, post-organ transplantation, and other compromised states
      have significant pleotropic immune defects that affect wound healing. In this
      work, we review the role of different immune cells in the regenerative process,
      highlight the effect of several common immunocompromised states on wound healing,
      and discuss different drug delivery strategies for overcoming immunodeficiencies.

PMID- 29221963
TI  - Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood
      Predicts Respiratory Allergy in Adolescence.
AB  - BACKGROUND: Sensitization in early childhood may precede respiratory allergy in
      adolescence. METHODS: IgE reactivity against 132 allergen molecules was evaluated
      using the MeDALL microarray in sera obtained from a random sample of 786 children
      at the age of 4, 8 and 16years in a population based birth cohort (BAMSE).
      Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. Clinically and
      independent relevant allergen molecules accounting for >=90% of IgE reactivities
      in sensitized individuals and at all time-points were identified as risk
      molecules and used to predict respiratory allergy. The data was replicated in the
      Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE
      reactivity with the use of a commercial IgE microarray. Sera were obtained from
      children at the ages of 3, 5, 8 and 11years (N=248) and the outcome was studied
      at 11years. FINDINGS: In the BAMSE cohort 4 risk molecules could be identified,
      i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS
      the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust
      mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE
      reactivity to >=3 of 4 allergen molecules at four years predicted incident and
      persistent asthma and/or rhinitis at 16years (87% and 95%, respectively). The
      corresponding proportions in the MAAS cohort at 16years were 100% and 100%,
      respectively, for IgE reactivity to >=3 of 5 risk molecules. INTERPRETATIONS: IgE
      reactivity to a few allergen molecules early in life identifies children with a
      high risk of asthma and/or rhinitis at 16years. These findings will be of
      importance for developing preventive strategies for asthma and rhinitis in
      children.

PMID- 29221965
TI  - Diffusion kurtosis imaging of a human nasopharyngeal carcinoma xenograft model:
      Initial experience with pathological correlation.
AB  - PURPOSE: The aim of this study was to investigate the relationship between
      diffusion kurtosis imaging (DKI)-related parameters and pathological measures
      using human nasopharyngeal carcinoma (NPC) xenografts in a nude mouse model.
      MATERIALS AND METHODS: Twenty-six BALB/c-nu nude mice were divided into two
      groups that were injected with two different nasopharyngeal squamous cell
      carcinoma cell lines (CNE1 and CNE2). DK magnetic resonance (MR) imaging was
      performed on a 3.0 Tesla MR scanner. DWI and DKI-related parameters, including
      apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis
      (MK) were measured. Mice were euthanatized when the maximum diameter of the
      primary tumor reached 1.5cm after MR scanning. Tumor tissues were then processed
      for hematoxylin and eosin staining. The pathological images were analyzed using a
      computer-aided pixel-wise clustering method to evaluate tumor cellular density,
      nuclei portion, cytoplasm portion, extracellular space portion, the ratio of
      nuclei to cytoplasm and the ratio of nuclei to extracellular space. The
      relationships between DWI and DKI-related parameters and pathological features
      were analyzed statistically. RESULTS: The ADC and MD values of the CNE1 group
      (1.16+/-0.24*10-3mm2/s, 2.28+/-0.29*10-3mm2/s) was higher than that of the CNE2
      group (0.82+/-0.14*10-3mm2/s, 1.53+/-0.24*10-3mm2/s, P<0.001), but the MK values
      between the two groups were not significantly different (CNE1: 0.55+/-0.14; CNE2:
      0.47+/-0.23; P>0.05). A Pearson test showed that the ADC and MD values were
      significantly correlated with cellular density, nuclei portion, extracellular
      space portion and the ratio of nuclei to extracellular space (r=-0.861; -0.909,
      P<0.001; r=-0.487; 0.591, P<0.05; r=0.567; 0.625, P<0.05; r=-0.645; -0.745,
      P<0.001, respectively). The MK values were significantly correlated with nuclei
      portion, cytoplasm portion and the ratio of nuclei to cytoplasm (r=-0.475,
      P<0.05; r=0.665, P<0.001; r=-0.494, P<0.05, respectively). CONCLUSION: The
      preliminary animal results suggest that DKI findings can provide valuable bio
      information for NPC tissue characterization. DKI imaging might be utilized as a
      surrogate biomarker for the non-invasive assessment of tumor microstructures.

PMID- 29221966
TI  - Lesion magnetic susceptibility response to hyperoxic challenge: A biomarker for
      malignant brain tumor microenvironment?
AB  - BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been previously
      used to differentiate lesions in patients with brain tumors. The aim of this work
      was to characterize the response of magnetic susceptibility differences in
      malignant brain tumors and surrounding edema to hyperoxic and hypercapnic
      respiratory challenges. METHODS: Images of malignant brain tumor patients (2
      glioblastoma multiforme, 2 anaplastic astrocytoma, 1 brain metastasis) with
      clinical MRI exams (contrast-enhanced T1w) were acquired at 3T. 3D multi-gradient
      echo data sets were acquired while the patients inhaled medical-air (21% O2),
      oxygen (100% O2), and carbogen (95% O2, 5% CO2). Susceptibility maps were
      generated from real and imaginary data. Regions of interest were analyzed with
      respect to respiration-gas-induced susceptibility changes. RESULTS: Contrast
      enhancing tumor regions with high baseline magnetic susceptibility exhibited a
      marked susceptibility reduction under hyperoxic challenges, with a stronger
      effect (-0.040 to -0.100ppm) under hypercapnia compared to hyperoxia (-0.010 to 
      0.067ppm). In contrast, regions attributed to necrotic tissue and to edema showed
      smaller changes of opposite sign, i.e. paramagnetic shift. There was a
      correlation between malignant tumor tissue magnetic susceptibility at baseline
      under normoxia and the corresponding susceptibility reduction under hypercapnia
      and - to a lesser degree - under hyperoxia. CONCLUSION: In this small cohort of
      analysis, quantification of susceptibility changes in response to respiratory
      challenges allowed a complementary, functional differentiation of tumorous sub
      regions. Those changes, together with the correlations observed between baseline
      susceptibility under normoxia and susceptibility reduction with challenges, could
      prove helpful for a non-invasive characterization of local tumor
      microenvironment.

PMID- 29221967
TI  - Improving Cognitive Function in Patients with Stroke: Can Computerized Training
      Be the Future?
AB  - BACKGROUND: Cognitive impairment after stroke is common and can cause disability
      with a high impact on quality of life and independence. Cognitive rehabilitation
      is a therapeutic approach designed to improve cognitive functioning after central
      nervous system's injuries. Computerized cognitive rehabilitation (CCR) uses
      multimedia and informatics resources to optimize cognitive compromised
      performances. The aim of this study is to evaluate the effects of pc cognitive
      training with Erica software in patients with stroke. METHODS: We studied 35
      subjects (randomly divided into 2 groups), affected by either ischemic or
      hemorrhagic stroke, having attended from January 2013 to May 2015 the Laboratory
      of Robotic and Cognitive Rehabilitation of Istituto di Ricerca e Cura a Carattere
      Scientifico Neurolesi in Messina. Cognitive dysfunctions were investigated
      through a complete neuropsychological battery, administered before (T0) and after
      (T1) each different training. RESULTS: At T0, all the patients showed language
      and cognitive deficits, especially in attention process and memory abilities,
      with mood alterations. After the rehabilitation program (T1), we noted a global
      cognitive improvement in both groups, but a more significant increase in the
      scores of the different clinical scales we administered was found after CCR.
      CONCLUSIONS: Our data suggest that cognitive pc training by using the Erica
      software may be a useful methodology to increase the post-stroke cognitive
      recovery.

PMID- 29221968
TI  - Clinical Study of Intravenous, Low-Dose Recombinant Tissue Plasminogen Activator
      for Acute Cerebral Infarction: Comparison of Treatment within 3 Hours versus 3
      4.5 Hours.
AB  - BACKGROUND: An intravenous recombinant tissue plasminogen activator (rt-PA,
      alteplase .6 mg/kg) for acute cerebral infarction within 3 hours of onset was
      approved in Japan in 2005. The treatment window was subsequently extended to
      within 4.5 hours of onset. However, few Japanese studies have compared the
      efficacy and safety of rt-PA therapy between patients treated within 3 hours and
      patients treated within 3-4.5 hours. METHODS: This study included 323 patients
      who received rt-PA for acute cerebral infarction within 3 hours or 3-4.5 hours
      between April 2007 and March 2017. Patients' characteristics, outcomes (modified
      Rankin Scale [mRS] score at 3 months), and symptomatic intracranial hemorrhage
      (sICH) were retrospectively investigated. RESULTS: Of the 323 patients, 219 were
      treated within 3 hours and 104 were treated at 3-4.5 hours. Among patients
      receiving rt-PA alone, 154 were treated within 3 hours (3-hour group), and 69
      were treated at 3-4.5 hours (3-4.5-hour group). There was no difference in the
      sICH rate (3.9% versus 4.3%, respectively; P = 1.00) or mRS score of 0-1 (38.3%
      versus 40.6%, respectively; P = .76) between these groups. In patients receiving
      additional neuroendovascular therapy, 65 were in the 3-hour group and 35 were in
      the 3-4.5-hour group. There was no significant difference in the sICH rate (1.5%
      versus 0%, respectively; P = 1.00) or mRS score of 0-1 (30.8% versus 31.4%,
      respectively; P = 1.00) between these groups. CONCLUSIONS: Low-dose rt-PA
      treatment from either 3 or 3-4.5 hours after acute cerebral infarction has the
      same efficacy and safety.

PMID- 29221970
TI  - Practical Application of Biogenic Amine Profiles for the Diagnosis of Patients
      with Ischemic Stroke.
AB  - BACKGROUND: Ischemic stroke (IS) is still one of the major issues in medicine.
      Still, early diagnosis and misdiagnosis remain the main barriers for proper
      patient treatment and follow-up. Exploring new potential diagnostic biomarkers
      for IS is relevant to decrease patient morbidity and the occurrence of poststroke
      diseases. Biomedical analysis could bring new light to the background of IS and
      in such a way-propose new bioanalytical tools for the early diagnosis,
      prognostication, and monitoring of IS. MATERIALS AND METHODS: This research aimed
      to present a discussion on the employment of biogenic amines (BAs), as well as
      their precursory amino acids and main metabolites, as a new panel of biomarkers
      for IS. Preliminary patient data were presented and the patients were described
      with respect to their clinical history and examination records, as well as
      scientific data gained from the liquid extraction-capillary electrophoresis
      determination of BAs in the patients' urine samples. RESULTS: The results showed
      the potential of BA screening using the developed sample preparation and analysis
      methods in urine during IS, and this will be further studied on a more numerous
      group of patients with IS to reveal the usefulness of BAs as a new panel of
      biomarkers for early IS diagnosis and prognostication. CONCLUSIONS: To our best
      knowledge, this methodology for the first time has been used for the simultaneous
      analysis of multiple small molecular biomarkers. In addition, the factors that
      might influence the determination of BAs in real samples were pointed out.

PMID- 29221969
TI  - Variability in Gastrostomy Tube Placement for Intracerebral Hemorrhage Patients
      at US Hospitals.
AB  - OBJECTIVE: We sought to characterize the variability among US hospitals with
      regard to gastrostomy tube placement for inpatients with intracerebral hemorrhage
      (ICH). METHODS: Using the Nationwide Inpatient Sample, we examined variations in
      the annual rate of gastrostomy tube placement from 2002 to 2011 for ICH patients
      admitted to hospitals with 30 or more annual ICH admissions. We then directly
      compared, among these hospitals, their individual frequencies of gastrostomy tube
      placement for ICH patients over the same time period. To quantify variability
      among hospitals, we used multilevel multivariable regression models accounting
      for a hospital random effect, adjusted for patient-level and hospital-level
      factors predictors of placement. RESULTS: Gastrostomy tube placement rates did
      not significantly change from 2002 to 2011 (9.8 to 8.7 per 100 admissions; P
      trend = .57). Among 690 hospitals with 38,080 ICH hospitalizations during this
      period, 10.4% of patients had a gastrostomy tube placed (n = 3976). Variation in
      the rate of placement among individual hospitals was large, from 0% to 34.4%
      (interquartile range 5.7%-13.6%). For a regression model controlling for patient
      and hospital covariates, the median odds ratio was 1.36 (95% confidence interval
      1.28-1.44), indicating that if a patient moved from one hospital to another with
      a higher intrinsic propensity of placement, there was a 1.36-fold median increase
      in the odds of receiving a gastrostomy tube, independent of patient and hospital
      factors. CONCLUSIONS: Variation in gastrostomy tube placement rates across
      hospitals is large and may in part reflect differences in local practice patterns
      or patient and surrogate preferences.

PMID- 29221971
TI  - Preventive Treatment with Lomerizine Increases Cerebral Blood Flows during the
      Interictal Phase of Migraine.
AB  - BACKGROUND: Changes in regional cerebral blood flow (rCBF) were reported in
      migraineurs. However, little is known how preventive medications of migraine can
      influence rCBF. Lomerizine, a calcium channel blocker, has been used for migraine
      prophylaxis in Japan. We examined rCBF after lomerizine treatment. SUBJECTS AND
      METHODS: Migraine was diagnosed according to the criteria of the International
      Classification of Headache Disorders, Third Edition beta. Migraine subtype was
      classified into migraine with aura (MA) and migraine without aura (MO).
      Lomerizine (10 mg/day, per oral) was administered for 3 months. Headache Impact
      Test-6 (HIT-6) and blood pressure (BP) were compared at baseline and end point.
      Brain single photon emission computed tomography using 99mTc-ethyl cysteinate
      dimer was performed at the interictal period. Brain SPECT data were analyzed
      according to revised version of 3-dimensional stereotaxic region of interest
      template. Clinic-radiological variables were analyzed by paired Student's t test.
      RESULTS: Ten migraineurs (4 men and 6 women) participated in the present study.
      Mean age was 54.1 (standard deviation [SD] 10.1) years. Mean duration of migraine
      was 25.3 (SD 9.8) years. Migraine subtype showed 4 MA and 6 MO patients. Mean
      score of HIT-6 was 66.3 (SD 11.7). Lomerizine treatment decreased HIT-6 scores
      significantly (P < .01). BP did not differ significantly after lomerizine
      treatment. Lomerizine treatment increased rCBF 20% approximately in the frontal,
      the parietal, the temporal, and the occipital region. CONCLUSIONS: The present
      study indicated a significant increase in interictal rCBF after lomerizine
      treatment in migraineurs. The upregulation of rCBF could contribute to the
      antimigraine mechanism of lomerizine.

PMID- 29221972
TI  - Angiopoietin-Like Proteins 4 (ANGPTL4) Gene Polymorphisms and Risk of Brain
      Arteriovenous Malformation.
AB  - BACKGROUND: Brain arteriovenous malformations (BAVMs) are formed by hypertrophied
      arterial vessels (afferents, feeders), a large number of arteriovenous shunts
      which become tangled to form a body (nidus) of malformation, which then expands
      draining proximal veins. The aim of this study was a replication of single
      nucleotide polymorphism (SNP) rs11672433 association with BAVM development with
      the subsequent meta-analysis of published data. METHODS: A total of 252 Russian
      patients with brain BAVMs and 480 control subjects were included in the present
      study. Genotyping was performed using real-time polymerase chain reaction with
      competitive hydrolysis probes. RESULTS: In our case-control study, we found no
      significant association with brain arteriovenous malformation for the SNP
      rs11672433 of ANGPTL4 gene (odds ratio .82, 95% confidence interval = .57-1.17 P
      value = .27) as well as in meta-analysis (odds ratio 1.18, 95% confidence
      interval = .81-1.73, P value = .39). CONCLUSIONS: Our data showed that SNP
      rs11672433 was not associated with the BAVM Russian population and the following
      meta-analysis did not detect an association in total. Thus, in spite of the fact
      that ANGPTL4 (protein) participates in the angiogenesis regulation processes, we
      consider that SNP rs11672433, a high-frequency locus in the ANGPTL4 gene, does
      not influence the predisposition to BAVM or its effect is too small to be
      detected in the present size sample set.

PMID- 29221973
TI  - Pathogens' toolbox to manipulate human complement.
AB  - The surveillance and pathogen fighting functions of the complement system have
      evolved to protect mammals from life-threatening infections. In turn, pathogens
      have developed complex molecular mechanisms to subvert, divert and evade the
      effector functions of the complement. The study of complement immunoevasion by
      pathogens sheds light on their infection drivers, knowledge that is essential to
      implement therapies. At the same time, complement evasion also acts as a
      discovery ground that reveals important aspects of how complement works under
      physiological conditions. In recent years, complex interrelationships between
      infection insults and the onset of autoimmune and complement dysregulation
      diseases have led to propose that encounters with pathogens can act as triggering
      factors for disease. The correct management of these diseases involves the
      recognition of their triggering factors and the development and administration of
      complement-associated molecular therapies. Even more recently, unsuspected
      proteins from pathogens have been shown to possess moonlighting functions as
      virulence factors, raising the possibility that behind the first line of
      virulence factors there be many more pathogen proteins playing secondary, helping
      and supporting roles for the pathogen to successfully establish infections. In an
      era where antibiotics have a progressively reduced effect on the management and
      control of infectious diseases worldwide, knowledge on the mechanisms of
      pathogenic invasion and evasion look more necessary and pressing than ever.

PMID- 29221974
TI  - Criteria for Postoperative Mechanical Ventilation After Thymectomy in Patients
      With Myasthenia Gravis: A Retrospective Analysis.
AB  - OBJECTIVE: To determine the criteria for postoperative mechanical ventilation
      after thymectomy in patients with Myasthenia Gravis. DESIGN: Retrospective study.
      SETTING: Teritiary care centre. PARTICIPANTS: 77 Myasthenia gravis patients
      operated for thymectomy were studied. INTERVENTIONS: After obtaining clearance
      from Institutional ethics committee, medical records of 77 patients with MG, who
      were operated for thymectomy between January 2005 and December 2015 were reviewed
      in a retrospective manner. Perioperative variables collected from the patient
      records were demographic data, duration of the disease, Osserman and Genkin
      classification, Anti-acetylcholine antibody (AChR) positivity, preoperative daily
      dose of drug, history of preoperative myasthenic crisis, preoperative vital
      capacity, technique of anesthesia, drugs used for anesthesia, perioperative
      complications, and duration of postoperative mechanical ventilation. The patients
      were divided into two groups, group I and group II consisting of those who
      required postoperative ventilation for < 300 minutes and > 300 minutes,
      respectively. The determinants of prolonged postoperative ventilation were
      studied. MEASUREMENTS AND MAIN RESULTS: The requirement of mechanical ventilation
      was higher in patients with higher Osserman's grade of myasthenia gravis.
      Duration of the disease had no effect on the duration of mechanical ventilation
      in myasthenic patients post thymectomy (p = 0.89). The patients with a
      preoperative history of myasthenic crisis had a requirement for prolonged
      mechanical ventilation (p=0.03). Patients with preoperative vital capacity < 2.9
      litres and preoperative CT scan showing thymoma had a requirement for prolonged
      mechanical ventilation with p values < 0.001 and 0.035, respectively. Patients
      who showed positivity for anti-acetylcholine antibodies had a prolonged
      mechanical ventilation (p=0.026). Preoperative dose of pyridostigmine and the
      choice of continuation or discontinuation of antcholinesterases on the day of
      surgery had no influence on the duration of mechanical ventilation (p value of
      0.19 and 0.36 respectively). Epidural analgesia intra and postoperatively
      significantly reduced the requirement of mechanical ventilation (p=0.006).
      CONCLUSION: The predictors of postoperative ventilation in myasthenic patients
      undergoing thymectomy as per our study are: 1. Grade of myasthenia; 2. History of
      preoperative myasthenic crisis; 3. Anti-acetylcholine antibodies positivity; 4.
      Presence of thymoma; and 5. a vital capacity < 2.9 litres. Use of thoracic
      epidural as a part of combined anesthetic technique helps to reduce the need of
      mechanical ventilation in these patients.

PMID- 29221975
TI  - A Story of Migration of a Surgically Implanted Aortic Sutureless Valve.

PMID- 29221976
TI  - Modeling Patient-Specific Deformable Mitral Valves.
AB  - Medical imaging has advanced enormously over the last few decades,
      revolutionizing patient diagnostics and care. At the same time, additive
      manufacturing has emerged as a means of reproducing physical shapes and models
      previously not possible. In combination, they have given rise to 3-dimensional
      (3D) modeling, an entirely new technology for physicians. In an era in which 3D
      imaging has become a standard for aiding in the diagnosis and treatment of
      cardiac disease, this visualization now can be taken further by bringing the
      patient's anatomy into physical reality as a model. The authors describe the
      generalized process of creating a model of cardiac anatomy from patient images
      and their experience creating patient-specific dynamic mitral valve models. This
      involves a combination of image processing software and 3D printing technology.
      In this article, the complexity of 3D modeling is described and the decision
      making process for cardiac anesthesiologists is summarized. The management of
      cardiac disease has been altered with the emergence of 3D echocardiography, and
      3D modeling represents the next paradigm shift.

PMID- 29221977
TI  - Re-examining Factors Associated With Mortality After Heart Transplantation: A
      Focus on Recipient Age and Relative Pulmonary Hypertension.

PMID- 29221978
TI  - Influence of 6% Hydroxyethyl Starch 130/0.4 Versus Crystalloid Solution on
      Structural Renal Damage Markers After Coronary Artery Bypass Grafting: A Post Hoc
      Subgroup Analysis of a Prospective Trial.
AB  - OBJECTIVE: The restriction of hydroxyethyl starch (HES) has mandated changes in
      volume management based on data of critically ill patients. Reliable data of
      structural renal damage after HES treatment in cardiac surgical patients are
      lacking. The influence of 6% HES 130/0.4 was investigated in this study. DESIGN:
      An exploratory post hoc subgroup analysis of a prospective trial was performed.
      SETTING: The study was carried out at a university hospital. PARTICIPANTS: Forty
      four low-risk cardiac surgical patients were examined. INTERVENTIONS: Twenty-two
      patients received only crystalloid solutions, and 22 were treated with balanced
      6% HES 130/0.4. MEASUREMENTS AND MAIN RESULTS: Functional renal parameters and
      the structural biomarkers alpha-glutathione S-transferase, kidney injury molecule
      1, liver fatty acid-binding protein, and neutrophil gelatinase-associated
      lipocalin were investigated. Volume balances, vasopressor dosages, blood losses,
      and coagulation parameters were compared. Most functional and structural renal
      parameters did not differ between the groups (serum creatinine p = 0.8380). Liver
      fatty acid-binding protein was transiently higher in the HES group only at 24
      hours postoperatively (p = 0.0002). No differences in mortality, acute kidney
      injury, and need for renal replacement therapy were observed. Blood coagulation
      was significantly more compromised in the HES group at intensive care unit
      arrival (factor II, p = 0.0012; factor X, p = 0.0031; thrombocytes, p = 0.0010).
      Blood losses, and vasopressor dosages tended to be higher in HES-treated patients
      without significance. CONCLUSION: Overall, the values and time courses of the
      biomarkers used did not indicate evidence of a mechanism for tubular injury
      caused by HES.

PMID- 29221979
TI  - Is Pulmonary Artery Catheter Placement in the Setting of Right Atrial Tumor
      Thrombus Worth the Risk?

PMID- 29221980
TI  - Coaptation Surface Area and Aortic Regurgitation: The Infinite Potential of
      Finite Element Analysis.

PMID- 29221981
TI  - Chest Computed Tomography Image for Accurately Predicting the Optimal Insertion
      Depth of Left-Sided Double-Lumen Tube.
AB  - OBJECTIVE: The main objective of this study was to assess the feasibility and
      accuracy of measuring the distance between the vocal cord and carina using chest
      computer tomography (CT) as a guide for the intubation of a left-sided double
      lumen tube (LDLT). DESIGN: Single-center, prospective, randomized study. SETTING:
      Local hospital in China. PARTICIPANTS: Sixty adult patients undergoing elective
      thoracic surgery requiring an LDLT for one lung ventilation were enrolled in this
      study. INTERVENTIONS: Patients were randomly allocated to the following 2 groups:
      blind intubation group (B group, n = 30) or chest computed tomography-guided
      group (C group, n = 30). The placement of the LDLT was accomplished using 1 of
      the 2 intubation methods. After intubation, an independent anesthesiologist
      evaluated the position of the LDLT and carina and bronchial injuries using fiber
      optic bronchoscopy. The number of optimal positions, the time for LDLT
      intubation, the time for fiber optic bronchoscope confirmation, and carina and
      bronchial injuries were recorded. RESULTS: Sixteen of 30 intubations in the B
      group were in optimal position, whereas 27 of 30 intubations in the C group were
      in optimal position; the difference was statistically significant (p < 0.01). The
      time for intubation of the LDLT took 118.0 +/- 26.2 seconds in the B group and
      71.5 +/- 8.7 seconds in the C group (p < 0.01). The time for position
      confirmation using fiber optic bronchoscope took 40.8 +/- 15.8 seconds in the B
      group and 18.7 +/- 7.9 seconds in the C group (p < 0.05). The incidences of
      carina and bronchial injuries were obviously lower in the C group (occurred in 3
      of 30 cases) than in the B group (11 of 30 cases) p < 0.05. The incidences of
      postoperative sore throat and hoarseness showed no significant differences
      between the 2 groups (p > 0.05). CONCLUSION: This study demonstrated that the
      method of measuring the distance between the vocal cord and carina according to
      the chest CT as a guide for the intubation of LDLT is more effective and more
      accurate than the blind intubation method.

PMID- 29221982
TI  - Hypothermic Cardiopulmonary Bypass Weaning and Prolonged Postoperative Rewarming
      in a Patient With Intraoperative Oxygenator Thrombosis.

PMID- 29221983
TI  - Medication related osteonecrosis of the jaws associated with targeted therapy as
      monotherapy and in combination with antiresorptives. A report of 7 cases from the
      Copenhagen Cohort.
AB  - OBJECTIVE: The aim of this study was to report cases of medication-related
      osteonecrosis of the jaws (MRONJ) associated with targeted therapy (TT) with or
      without concomitant antiresorptive treatment, among the Copenhagen ONJ cohort,
      which includes all consecutive cases of MRONJ seen in Copenhagen. STUDY DESIGN:
      We retrospectively studied the treatment of 204 consecutive patients with MRONJ,
      seen between January 2010 and May 2016, to identify those associated with TT.
      RESULTS: We detected 7 cases of MRONJ associated with TT (3.4%). Four patients
      received TT only, whereas 3 were concomitantly treated with bisphosphonates (n =
      3) and/or denosumab (n = 3). The TT regimens included sunitinib (Sutent) (n = 1),
      everolimus (Afinitor) (n = 1), erlotinib (Tarceva) (n = 1), bevacizumab (Avastin)
      (n = 3), dasatinib (Sprycel) (n = 1) and imatinib (Glivec) (n = 1). The MRONJ
      stage included stages 1 and 2, and mean score on the visual analogue scale for
      pain in the jaw was 4.0. CONCLUSIONS: Health care providers should be aware of
      the possibility of MRONJ associated with the TT agents sunitinib, everolimus, and
      dasatinib and uncommon cancer types, including renal cell carcinoma, non-small
      cell lung cancer, glioblastoma, and leukemia, where MRONJ may also occur.

PMID- 29221984
TI  - Accounting for apparent deviations between calorimetric and van't Hoff
      enthalpies.
AB  - BACKGROUND: In theory, binding enthalpies directly obtained from calorimetry
      (such as ITC) and the temperature dependence of the binding free energy (van't
      Hoff method) should agree. However, previous studies have often found them to be
      discrepant. METHODS: Experimental binding enthalpies (both calorimetric and van't
      Hoff) are obtained for two host-guest pairs using ITC, and the discrepancy
      between the two enthalpies is examined. Modeling of artificial ITC data is also
      used to examine how different sources of error propagate to both types of binding
      enthalpies. RESULTS: For the host-guest pairs examined here, good agreement, to
      within about 0.4kcal/mol, is obtained between the two enthalpies. Additionally,
      using artificial data, we find that different sources of error propagate to
      either enthalpy uniquely, with concentration error and heat error propagating
      primarily to calorimetric and van't Hoff enthalpies, respectively. CONCLUSIONS:
      With modern calorimeters, good agreement between van't Hoff and calorimetric
      enthalpies should be achievable, barring issues due to non-ideality or
      unanticipated measurement pathologies. Indeed, disagreement between the two can
      serve as a flag for error-prone datasets. A review of the underlying theory
      supports the expectation that these two quantities should be in agreement.
      GENERAL SIGNIFICANCE: We address and arguably resolve long-standing questions
      regarding the relationship between calorimetric and van't Hoff enthalpies. In
      addition, we show that comparison of these two quantities can be used as an
      internal consistency check of a calorimetry study.

PMID- 29221986
TI  - Streptococcus pneumoniae two-component regulatory systems: The interplay of the
      pneumococcus with its environment.
AB  - Streptococcus pneumoniae is a human pathobiont possessing a diverse array of
      multifunctional proteins essential for bacterial fitness and virulence. Gene
      expression is tightly controlled by regulatory components and among the
      pneumococcal sensorial tools, two-component regulatory systems (TCS) are the most
      widespread and conserved. This review aims to provide a comprehensive analysis of
      original studies on pneumococcal TCS on a functional level. Despite a rather
      chaotic nomenclature, the current available information on pneumococcal
      regulation by these systems can be conveniently addressed, according to the
      regulation of pathophysiological cell processes and the responses to detectable
      environmental signals. Pneumococcal pathophysiological processes driven by TCS
      can be further categorized into competence and fratricide, bacteriocin
      production, and virulence factors expression. Conversely, detectable
      environmental signals by pneumococci can be grouped into antibiotics and cell
      wall perturbations, environmental stress, and nutrients acquisition. This review
      summarizes the state of the art on pneumococcal TCS based on an integral approach
      and thus providing insights into the regulatory network(s) of S. pneumoniae.

PMID- 29221985
TI  - HOTAIR-mediated reciprocal regulation of EZH2 and DNMT1 contribute to polyphyllin
      I-inhibited growth of castration-resistant prostate cancer cells in vitro and in
      vivo.
AB  - BACKGROUND: Polyphyllin I (PPI), one of the steroidal saponins in paris
      polyphylla, has been reported to exhibit antitumor effects. However, the detailed
      molecular mechanism underlying this has not been elucidated. METHODS: Cell
      viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol
      2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Flow cytometry assays,
      respectively. Cell invasion and migration were examined by Transwell invasion and
      wound healing assays. Western blot analysis was performed to examine the protein
      expressions of zeste homolog 2 (EZH2), DNA methyltransferase 1 (DNMT1). QRT-PCR
      was used to examine the levels of long non-coding RNA (lncRNA) HOX transcript
      antisense RNA (HOTAIR). Small interfering RNAs (siRNAs) method was used to
      knockdown HOTAIR. Exogenously expressions of HOTAIR, DNMT1 and EZH2 were carried
      out by Transient transfection assays. EZH2 promoter activity was measured by
      Secrete-Pair Dual Luminescence Assay Kit. A nude mice xenograft model was used to
      confirm the findings in vitro. RESULTS: We showed that PPI significantly
      inhibited growth, induced cell cycle arrest of castration-resistant prostate
      cancer (CRPC) cells. In addition, PPI also reduced the migration and invasion in
      CRPC cells. In mechanism, we found that PPI decreased the protein expressions of
      EZH2, DNMT1 and levels of HOTAIR. Interestingly, silenced HOTAIR reduced EZH2 and
      DNMT1 protein expressions. On the contrary, exogenously expressed HOTAIR resisted
      PPI-inhibited EZH2 and DNMT1 protein expressions, EZH2 promoter activity and cell
      growth. Moreover, excessive EZH2 antagonized PPI-suppressed DNMT1 protein
      expression or vice versa. Consistent with this, PPI inhibited tumor growth,
      HOTAIR, the protein expressions of DNMT1 and EZH2 in vivo. CONCLUSION: Our
      results show that PPI inhibits growth of CRPC cells through inhibition of HOTAIR
      expression, subsequently; this results in the repression of DNMT1 and EZH2
      expressions. The interactions among HOTAIR, DNMT1 and EZH2, and reciprocal
      regulation of DNMT1 and EZH2 contribute to the overall responses of PPI. This
      study reveals a novel mechanism for HOTAIR-mediated regulating DNMT1 and EZH2 in
      response to PPI in inhibition of the growth of CRPC cells.

PMID- 29221988
TI  - Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress
      induced myocardial apoptosis.
AB  - Mounting evidence has strongly implicated oxidative stress in the development of
      cardiac dysfunction, and myocardial apoptosis contributes to the pathogenesis of
      heart failure. Quantitative cardiac proteomics data revealed that pressure load
      by TAC resulted in a significant decline in mitochondrial metabolic activity,
      where TIIA (Tanshinone IIA sulfonate) treatment reversed it in vivo, which might
      be mediated by Nrf2. In NRVMs, TIIA treatment ameliorated H2O2-induced caspase
      3/9 activations through the suppression of p38 and mTOR signaling pathways, where
      caspase-mediated cleavage of YY1 and PARP resulted in the defects in
      mitochondrial biogenesis and DNA repair, and this event finally led to
      cardiomyocyte apoptosis. Mass spectrometry analysis showed that TIIA
      hydrophobically interacted with Keap1 (the cytoplasmic repressor of Nrf2) and
      induced its degradation in vitro. Site-directed mutagenesis of Keap1 identified
      V122/V123/I125 to be the critical residues for the TIIA-induced de-dimerization
      and degradation of Keap1. Besides, TIIA treatment also epigenetically up
      regulated Nrf2 gene transcription, where it hypomethylated the first 5 CpGs of
      Nrf2 promoter. Furthermore, cardiac-specific Nrf2 knockout mice exhibited the
      significantly dampened anti-apoptotic effects of TIIA.

PMID- 29221989
TI  - Differential targeting of membrane lipid domains by caffeic acid and its ester
      derivatives.
AB  - Phenolic acids have been associated to a wide range of important health benefits
      underlain by a common molecular mechanism of action. Considering that significant
      membrane permeation is prevented by their hydrophilic character, we hypothesize
      that their main effects result from the interplay with cell membrane surface.
      This hypothesis was tested using the paradigmatic caffeic acid (CA) and two of
      its ester derivatives, rosmarinic (RA) and chlorogenic (CGA) acids, for which we
      predict, based on molecular dynamics simulations, a shallow location in
      phospholipid bilayers dependent on the protonation-state. Using complementary
      experimental approaches, an interaction with the membrane was definitely revealed
      for the three compounds, with RA exhibiting the highest lipid bilayer partition,
      and the redox signals of membrane-bound RA and CA being clearly detected.
      Cholesterol decreased the compounds bilayer partition, but not their ability to
      lower membrane dipole potential. In more complex membrane models containing also
      sphingomyelin, with liquid disordered (ld)/ liquid ordered (lo) phases
      coexistence, mimicking domains in the external leaflet of human plasma membrane,
      all compounds were able to affect nanodomains lateral organization. RA, and to a
      lesser extent CGA, decreased the size of lo domains. The most significant effect
      of CA was the possible formation of a rigid gel-like phase, enriched in
      sphingomyelin. In addition, all phenolic acids decreased the order of lo domains.
      In sum, phenolic acid effects on the membrane are enhanced in cholesterol-rich lo
      phases, which predominate in the outer leaflet of human cell membranes and are
      involved in many key cellular processes.

PMID- 29221987
TI  - Hierarchical recognition of amino acid co-germinants during Clostridioides
      difficile spore germination.
AB  - Bile acids are an important signal for germination of Clostridioides difficile
      spores; however, the bile acid signal alone is not sufficient. Amino acids, such
      as glycine, are another signal necessary for germination by C. difficile spores.
      Prior studies on the amino acid signal required for germination have shown that
      there is a preference for the amino acid used as a signal for germination.
      Previously we found that d-alanine can function as a co-germinant for C.
      difficile spores at 37  degrees C but not at 25  degrees C. Here, we tested the
      ability of other amino acids to act as co-germinants with taurocholate (TA) at 37
      degrees C and found that many amino acids previously categorized as non-co
      germinants are co-germinants at 37  degrees C. Based on the EC50 values
      calculated for two different strains, we found that C. difficile spores recognize
      different amino acids with varying efficiencies. Using this data, we ranked the
      amino acids based on their effect on germination and found that in addition to d
      alanine, other D-forms of amino acids are also used by C. difficile spores as co
      germinants. Among the different types of amino acids, ones with branched chains
      such as valine, leucine, and isoleucine are the poorest co-germinants. However,
      glycine is still the most effective amino acid signal for both strains. Our
      results suggest that the yet-to-be-identified amino acid germinant receptor is
      highly promiscuous.

PMID- 29221990
TI  - Molecular and cellular mechanisms of chemoresistance in pancreatic cancer.
AB  - Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant
      cancers, and current therapies targeting cancer-associated molecular pathways
      have not given satisfactory results, owing in part to rapid upregulation of
      alternative compensatory pathways. Most of the available treatments are
      palliative, focussing on improving the quality of life. At present, available
      options are surgery, embolization, radiation, chemotherapy, immunotherapy and use
      of other more targeted drugs. In this review, we describe the cellular and
      molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX
      (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE
      (nab-Paclitaxel), which have shown a survival benefit, although modest, for
      pancreatic cancer patients. Nevertheless, gemcitabine remains the standard first
      line option for advanced-stage pancreatic cancer patients and, as resistance to
      the drug has attracted an increasing scientific interest, we deliberate on the
      main intracellular processes and proteins vital in acquired chemoresistance to
      gemcitabine. Lastly, our review examines various microenvironmental factors
      capable of instigating PDAC to develop resistance to chemotherapeutic drugs.

PMID- 29221991
TI  - On the Production of Chitosan-Coated Polycaprolactone Nanoparticles in a Confined
      Impinging Jet Reactor.
AB  - This work is focused on the synthesis of polycaprolactone nanoparticles, coated
      with chitosan, in a confined impinging jet reactor using the solvent displacement
      method. The role of the various reacting species was investigated, evidencing
      that a biocompatible polymer, for example, polycaprolactone, is required to
      support chitosan to obtain a monomodal particle size distribution, with low
      particle diameters. A surfactant is required to reduce the nanoparticle size
      (down to a mean diameter of about 260 nm) and obtain a positive zeta potential
      (about +31 mV), perfectly suitable for pharmaceutical applications. Different
      surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl
      alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg
      mL-1) and of chitosan (in the range 1.5-5 mg mL-1) on both the mean particle size
      and zeta potential was also investigated, evidencing that chitosan concentration
      has the strongest effect on both parameters. Finally, the effect of solvent
      evaporation, quenching and feed flow rate was investigated, showing that the
      evaporation stage does not affect particle characteristics, quenching is required
      to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min-1 is
      required in the considered reactor to minimize the particle size.

PMID- 29221992
TI  - Active Mediated Transport of Chloramphenicol and Thiamphenicol in a Calu-3 Lung
      Epithelial Cell Model.
AB  - Pulmonary administration enables high local concentrations along with limited
      systemic side effects but not all antibiotics could be good candidates. In this
      perspective, diffusion of the antibiotic chloramphenicol (CHL) and thiamphenicol
      (THA) through the lung has been evaluated to reassess their potential for
      pulmonary administration. The apparent permeability (Papp) was evaluated with the
      Calu-3 cell model. The influence of drug transporters was assessed with the PSC
      833, MK-571, and KO-143 inhibitors. The influence of CHL and THA on the cell
      uptake of rhodamin 123 and fluorescein was also evaluated. Absorptive Papp of CHL
      and THA was concentration independent with CHL Papp 4 times higher than that of
      THA. Secretory Papp of CHL was concentration independent, whereas it was
      concentration dependent for THA with an efflux ratio of 3.6 for the lowest
      concentration. The use of inhibitors suggested that CHL and THA were substrates
      of efflux transporters but with a low affinity. In conclusion, the permeability
      results suggest that the pulmonary route may offer a biopharmaceutical advantage
      only for THA. Owing to the influence of drug transporters, a higher concentration
      in the lung than in the plasma is expected mostly for THA, whatever the route of
      administration.

PMID- 29221993
TI  - Accuracy of Tubal Patency Assessment in Diagnostic Hysteroscopy Compared with
      Laparoscopy in Infertile Women: A Retrospective Cohort Study.
AB  - STUDY OBJECTIVE: To evaluate whether the presence of a visualizable "flow" effect
      in the fallopian tube ostia in hysteroscopic routine evaluation is predictive of
      tube patency. DESIGN: A retrospective cohort study (Canadian Task Force
      Classification II-2). SETTING: Data from all patients who underwent surgery
      because of infertility at the study center between 2008 and 2016 were analyzed
      retrospectively. The main outcome parameter was fallopian tube patency as
      assessed by laparoscopic chromopertubation. The predictive parameters tested were
      the presence of hysteroscopic tube "flow," general patient characteristics, and
      intraoperative findings. PATIENTS: Five hundred eleven infertile women who
      underwent combined hysteroscopy and laparoscopy were included. INTERVENTIONS: All
      women underwent combined hysteroscopy and laparoscopy. Some had other
      interventions when necessary, but no additional interventions were taken because
      of this study. RESULTS: In an analysis of 998 fallopian tubes, the hysteroscopic
      assessment of fallopian tube "flow" was highly accurate in predicting fallopian
      tube patency (p < .001), with a sensitivity of 86.4% (95% confidence interval
      [CI], 83.7-88.8) and a specificity of 77.6% (95% CI, 72.1-82.5). Risk factors for
      a false-negative hysteroscopy result were the presence of uterine myomas (odds
      ratio [OR] = 2.11; 95% CI, 1.10-4.05; p = .025), the presence of a hydrosalpinx
      on the analyzed side (OR = 2.50, 95% CI, 1.17-5.34; p = .019), and the presence
      of peritubal adhesions surrounding the analyzed tube (OR = 2.87; 95% CI, 1.21
      6.76; p = .016). CONCLUSION: A visualizable tube "flow" in hysteroscopy was
      accurate in the prediction of tubal patency, with a positive predictive value of
      about 91%. Knowledge about hysteroscopic fallopian tube "flow" can help to plan
      the future approach in an individual patient.

PMID- 29221994
TI  - Allele and haplotype diversity of 12 X-STRs in Sardinia.
AB  - The analysis of clusters of tightly linked X-chromosome short tandem repeat (STR)
      markers can assist the interpretation of complex kinship cases. However, when
      linkage disequilibrium (LD) is present in the population of origin of tested
      individuals, haplotype rather than allele frequencies should be used in
      likelihood calculations. The diversity of twelve X-STRs arranged in four linkage
      groups (I: DXS10148-DXS10135-DXS8378; II: DXS7132-DXS10079-DXS10074; III:
      DXS10103-HPRTB-DXS10101; IV: DXS10146-DXS10134-DXS7423) was tested in a Sardinian
      population sample (n=516) including three open populations from the Northern,
      Central and Southern part of the island, and three isolates (Benetutti, Desulo,
      Carloforte). Evidence of LD was detected in Sardinia within each linkage group.
      Significant differences in haplotype and allele frequency distribution of X-STR
      markers was seen between isolates and open populations, which on the contrary
      appeared highly homogeneous. The percentage of Sardinian haplotypes previously
      unobserved in a similar dataset compiled for the Italian population was: 76.3%
      (linkage group I), 61.3% (linkage group II), 54.1% (linkage group III), 58.9%
      (linkage group IV). Significant pairwise genetic differences were seen between
      mainland Italy, the three Sardinian isolates, and the open population of Southern
      Sardinia. The study confirms the presence of high levels and complex patterns of
      LD along the X chromosome in Sardinia, and provides population-specific haplotype
      data for biostatistical evaluation in kinship testing.

PMID- 29221995
TI  - Antimicrobial susceptibility testing of colistin - evaluation of seven commercial
      MIC products against standard broth microdilution for Escherichia coli,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp.
AB  - OBJECTIVE: Both EUCAST and CLSI recommend broth microdilution (BMD) for
      antimicrobial susceptibility testing of colistin, but BMD is rarely used in
      routine microbiology laboratories. The objective of this study was to evaluate
      five commercially available BMD products and two brands of gradient tests for
      colistin MIC determination using BMD according to ISO standard 20776-1 as
      reference. METHODS: Colistin MIC determination was performed according to the
      manufacturer's instructions on five commercially available BMD products
      (Sensititre, MICRONAUT-S, MICRONAUT MIC-Strip, SensiTest, and UMIC) and two
      gradient tests (Etest and MIC Test Strip). Colistin reference MICs were
      determined using frozen panels according to ISO standard 20776-1. An
      international collection of Gram-negative bacteria (n=75) with varying levels of
      colistin susceptibility was tested. RESULTS: The colistin BMD products correlated
      well with reference tests, in particular for Sensititre and the two MICRONAUT
      products (essential agreement >=96%: 66/69 (96%, CI 88-99%), 72/75 (96%, CI 88
      99%) and 74/75 (99%, CI 92-100%)). The results were somewhat poorer for the BMD
      products SensiTest and UMIC: EA 88% (51/58, CI 77-95%) and 82% (61/74, CI 72
      89%), respectively), and considerably poorer for the gradient tests (EA 43-71%
      depending on gradient test and Mueller-Hinton agar manufacturer). The gradient
      tests generally underestimated colistin MICs, resulting in a significant number
      of false susceptible results (9-18 of total 75 tests, compared with 1-3 for the
      BMD products). CONCLUSIONS: Based on the results of this study, we advise
      laboratories not to trust gradient tests for colistin susceptibility testing and
      to use broth microdilution methods for this purpose. There are several commercial
      broth microdilution tests available and in principle they perform well.

PMID- 29221997
TI  - What Do Patients Want to Know? Questions and Concerns Regarding Mammography
      Expressed Through Social Media.
AB  - PURPOSE: The purpose of this project is to identify questions and concerns
      patients have regarding breast cancer screening mammography to establish
      priorities in patient education and health care communication. METHODS: A content
      analysis of posted questions (June 2010 to February 2017) containing the keywords
      mammogram and mammography was conducted on the social media question and answer
      website Quora (Quora Inc, Mountainview, California). Question topic, responses,
      and number of views were recorded. Comparisons were made by respondent type
      (medical professional or nonmedical professional) for screening recommendations
      and accompanying evidence. Descriptive statistics were employed to summarize the
      results. RESULTS: Overall, 197,620 views of mammography-related questions were
      identified, focused on 51 questions and 172 responses (51 of 172 [29.7%] by
      medical professionals [n = 25]; 121 of 172 [70.3%] by nonmedical professionals [n
      = 121]). Mammographic efficacy (16 of 51 [31.4%]) and screening guidelines (10 of
      51 [19.6%]) were the most frequently queried topics. Overall, the majority of
      respondents were supportive of screening mammography. Most medical professionals
      recommended screening mammography starting at age 40, even after revisions in
      guidelines. Among nonmedical professionals, 4 of 22 (18.2%) were against
      screening mammography with less consensus regarding appropriate age of initial
      screen. Health society websites and journal articles were the most commonly
      referenced sources among medical and nonmedical professionals, respectively.
      CONCLUSION: A considerable interest in screening mammography guidelines and
      mammographic efficacy exists among users who seek health information on a social
      media question and answer website. Awareness of such platforms allows a unique
      opportunity for targeted health education and dissemination of accurate
      information, which may be able to reach a potentially untapped or hard-to-reach
      patient population.

PMID- 29221998
TI  - Locoregional Failure Rounds: A Meaningful Quality Improvement Project.

PMID- 29221996
TI  - Vitrification, not cryoprotectant exposure, alters the expression of
      developmentally important genes in in vitro produced porcine blastocysts.
AB  - The vitrification of embryos is common practice in advanced livestock breeding
      programs and in human fertility clinics. Recent studies have revealed that
      vitrification results in aberrant expression of a number of stress related genes.
      However, few studies have examined the effect that vitrification has on
      developmentally important genes, and none have been conducted in porcine embryos.
      The aim of this study was to determine the effects that different vitrification
      procedures and cryoprotectant combinations have on the expression of imprinted
      genes in in vitro produced (IVP) porcine blastocysts. The transcript levels of
      insulin-like growth factor 2 (IGF2) were lower in all groups of vitrified
      blastocysts compared to that in non-vitrified control blastocysts (P < 0.05).
      Expression levels of IGF2 and IGF2 receptor (IGF2R) in blastocysts that had been
      exposed to cryoprotectants without being vitrified were similar to that in non
      vitrified control blastocysts (P > 0.05). Furthermore, blastocysts vitrified
      using ethylene glycol and propanediol combined, and those vitrified in a closed
      device, had IGF2R transcript levels similar to that in non-vitrified control
      blastocysts (P > 0.05). In conclusion, vitrification, but not exposure to
      cryoprotectants, caused aberrant expression of the imprinted genes IGF2 and
      IGF2R. Vitrification protocols that incorporated propanediol or a closed device
      were found to be least disruptive of gene expression in IVP porcine blastocysts.

PMID- 29221999
TI  - Supporting Imagers' VOICE: A National Training Program in Comparative
      Effectiveness Research and Big Data Analytics.
AB  - Provided methodologic training, more imagers can contribute to the evidence basis
      on improved health outcomes and value in diagnostic imaging. The Value of Imaging
      Through Comparative Effectiveness Research Program was developed to provide hands
      on, practical training in five core areas for comparative effectiveness and big
      biomedical data research: decision analysis, cost-effectiveness analysis,
      evidence synthesis, big data principles, and applications of big data analytics.
      The program's mixed format consists of web-based modules for asynchronous
      learning as well as in-person sessions for practical skills and group discussion.
      Seven diagnostic radiology subspecialties and cardiology are represented in the
      first group of program participants, showing the collective potential for greater
      depth of comparative effectiveness research in the imaging community.

PMID- 29222000
TI  - The Triumph of the Machines.

PMID- 29222001
TI  - The Hatfields, the McCoys, and Anthem's New Policy for Advanced Diagnostic
      Imaging.

PMID- 29222003
TI  - The McDonaldization of Radiology.

PMID- 29222002
TI  - Impact of Simulation-Based Training on Radiology Trainee Education in Ultrasound
      Guided Breast Biopsies.
AB  - PURPOSE: The aim of this study is to determine the impact of a simulation-based
      ultrasound-guided (USG) breast biopsy training session on radiology trainee
      procedural knowledge, comfort levels, and overall procedural confidence and
      anxiety. METHODS: Twenty-one diagnostic radiology residents from a single
      academic institution were recruited to participate in an USG breast biopsy
      training session. The residents filled out a questionnaire before and after the
      training session. Ten multiple-choice questions tested general knowledge in
      diagnostic breast ultrasound and USG breast biopsy concepts. Subjective comfort
      levels with ultrasound machine and biopsy device functionality, patient
      positioning, proper biopsy technique, image documentation, needle safety and
      overall procedural confidence and anxiety levels were reported on a 5-point
      Likert scale before and after training. RESULTS: Participants demonstrated
      significant improvement in number of correctly answered general knowledge
      questions after training (P < .0001). Significant improvement was seen in
      resident comfort level in ultrasound machine functionality, patient positioning,
      biopsy device functionality, biopsy technique, image documentation, as well as
      overall confidence level (all P < .05). Participants indicated a slight but not
      significant reduction in anxiety levels (P = .27). CONCLUSIONS: A simulation
      based USG breast biopsy training session may improve radiology trainee procedural
      knowledge, comfort levels, and overall procedural confidence.

PMID- 29222004
TI  - Declining Interest in Pediatric Radiology Prompts a Call to Action.

PMID- 29222005
TI  - Does Involvement in Global Health Reduce Perceived Radiologist Burnout?

PMID- 29222006
TI  - Wrist Accelerometry for Physical Activity Measurement in Individuals With Spinal
      Cord Injury-A Need for Individually Calibrated Cut-Points.
AB  - OBJECTIVE: To create and compare individual and group-based cut-points for wrist
      accelerometry that correspond to moderate-to-vigorous physical activity (MVPA) in
      people with spinal cord injury (SCI). DESIGN: Participants completed a graded
      treadmill-wheeling test while being assessed for oxygen consumption, wrist
      acceleration vector magnitude, and spoke acceleration. Oxygen consumption was
      converted to SCI metabolic equivalents (METs), and linear regression was applied
      to determine an individualized vector magnitude cut-point (counts per minute, VM
      CPM) corresponding with MVPA (>=3 SCI METs). Multilevel linear regression was
      applied to determine a group MVPA cut-point. Participants then completed a 6-day
      monitoring period while wearing the accelerometers. SETTING: A local SCI research
      center. PARTICIPANTS: Manual wheelchair users (N=20; aged 31-64y; injury levels,
      C5 to L2) with chronic (>1y) SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Mean total daily MVPA, wheeled MVPA, and nonwheeled MVPA were
      calculated using both the individual and group cut-points. Agreement on measures
      of minutes per day of MVPA between the individual and group mean cut-point method
      was assessed using Bland-Altman plots. RESULTS: Individual cut-points for MVPA
      ranged from 6040 to 21,540 VM-CPM, with a group cut-point of 11,652 (95%
      confidence interval, 7395-15,909). For total daily MVPA, Bland-Altman analysis
      revealed a bias of .22+/-33.0 minutes, with 95% limits of agreement from -64.5 to
      64.9 minutes, suggesting a large discrepancy between total MVPA calculated from
      individual and group mean cut-points. CONCLUSIONS: Individual calibration of
      wrist-worn accelerometry is recommended for effective habitual PA monitoring in
      this population.

PMID- 29222007
TI  - Current Concepts in Pathogenesis, Diagnosis, and Management of Smoking-Related
      Interstitial Lung Diseases.
AB  - Tobacco exposure results in various changes to the airways and lung parenchyma.
      Although emphysema represents the more common injury pattern, in some
      individuals, cigarette smoke injures alveolar epithelial cells and other lung
      cells, resulting in diffuse infiltrates and parenchymal fibrosis. Smoking can
      trigger interstitial injury patterns mediated via recruitment and inappropriate
      persistence of myeloid and other immune cells, including eosinophils. As our
      understanding of the role of cigarette smoke constituents in triggering lung
      injury continues to evolve, so does our recognition of the spectrum of smoking
      related interstitial lung changes. Although respiratory bronchiolitis
      interstitial lung disease, desquamative interstitial pneumonia, pulmonary
      Langerhans cell histiocytosis, and acute eosinophilic pneumonia have a well
      established association with tobacco use, its role and impact on idiopathic
      pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and connective
      tissue disease-related interstitial lung diseases is still ambiguous. Smoking
      related interstitial fibrosis is a relatively newly appreciated entity with
      distinct histopathologic features but with unclear clinical ramifications.
      Increased implementation of lung cancer screening programs and utilization of CT
      scans in thoracic imaging have also resulted in increased identification of
      "incidental" or "subclinical" interstitial lung changes in smokers, the ensuing
      impact of which remains to be studied.

PMID- 29222008
TI  - Gait Speed: Validity of Measurement in Patients With Severe Chronic Lung Disease,
      Including Prognostic and Practical Implications.
AB  - Gait speed is used increasingly to predict function and future well-being among
      healthy elderly people as well as for those with long-term medical conditions.
      When selecting outcome measures such as walking speed, it is important to include
      the circumstances under which the measurement is made to avoid bias and ensure
      accurate recommendations. We completed a retrospective chart review of walking
      test results from patients with chronic lung disease to demonstrate the practical
      implications of reporting gait speed from either a standing or walking start. In
      this cohort of 99 patients (55 with COPD), gait speed from a standing start
      underestimated usual gait speed (difference = 6.1 m/min [5.3-6.9 m/min]) with
      poor agreement (8 m/min [6.6-9.4 m/min]) between the two methods of reporting
      speed. The standing start speed incorrectly identified some patients as at higher
      risk for poor health. In a practical example, gait speed from a standing start
      produced 11 false-negative evaluations of the ability to complete a road crossing
      at usual speed. We present walking speeds using both methods, which illustrate
      the importance of construct validity and measurement protocol.

PMID- 29222009
TI  - Redefining the phenotypic spectrum of de novo heterozygous CDK13 variants: Three
      patients without cardiac defects.
AB  - Recently, 7 patients with de novo constitutional non-synonymous mutations in the
      CDK13 gene were ascertained through a trio exome analysis of a large cohort of
      610 patients with congenital cardiac diseases. Despite another report describing
      9 additional patients, the clinical spectrum of this condition has yet to be
      defined. Herein, we report 3 patients with heterozygous constitutional CDK13
      mutations, who were ascertained through exome analysis of children with
      intellectual disability and minor anomalies, who lacked cardiac anomalies. Two
      patients had a c.2149G > A, p.Gly717Arg mutation, and one had a c.2525A > G, p.
      Asn842Ser mutation. A review of the previously described patients and those
      described herein has enabled the following points to be clarified. First,
      congenital heart diseases are not an essential feature (13/19). Second, nasal
      features may help syndromic recognition (14/16). Third, widely spaced and peg
      shaped teeth may represent a previously unappreciated diagnostic clue for this
      newly identified syndrome. Here, we show that p.Gly717Arg represents a hotspot in
      addition to p.Asn842Ser. We suggest that this CDK13-related disorder may
      represent a clinically recognizable syndrome.

PMID- 29222010
TI  - A novel NR2F2 loss-of-function mutation predisposes to congenital heart defect.
AB  - Congenital heart defect (CHD) is the most common type of birth defect in humans
      and a leading cause of infant morbidity and mortality. Previous studies have
      demonstrated that genetic defects play a pivotal role in the pathogenesis of CHD.
      However, the genetic basis of CHD remains poorly understood due to substantial
      genetic heterogeneity. In this study, the coding exons and splicing boundaries of
      the NR2F2 gene, which encodes a pleiotropic transcription factor required for
      normal cardiovascular development, were sequenced in 168 unrelated patients with
      CHD, and a novel mutation (c.247G > T, equivalent to p.G83X) was detected in a
      patient with double outlet right ventricle as well as ventricular septal defect.
      Genetic scanning of the mutation carrier's relatives available showed that the
      mutation was present in all affected family members but absent in unaffected
      family members. Analysis of the index patient's pedigree displayed that the
      mutation co-segregated with CHD, which was transmitted as an autosomal dominant
      trait with complete penetrance. The nonsense mutation was absent in 230
      unrelated, ethnically-matched healthy individuals used as controls. Functional
      deciphers by using a dual-luciferase reporter assay system revealed that the
      mutant NR2F2 protein had no transcriptional activity as compared with its wild
      type counterpart. Furthermore, the mutation abrogated the synergistic
      transcriptional activation between NR2F2 and GATA4, another core cardiac
      transcription factor associated with CHD. This study firstly associates NR2F2
      loss-of-function mutation with an increased susceptibility to double outlet right
      ventricle in humans, which provides further significant insight into the
      molecular mechanisms underpinning CHD, suggesting potential implications for
      genetic counseling of CHD families and personalized treatment of CHD patients.

PMID- 29222011
TI  - Preparation, characterization and antioxidant activity of polysaccharide from
      Fallopia multiflora (Thunb.) Harald.
AB  - This study aimed to investigate antioxidant activities of a polysaccharide from
      Fallopia multiflora (Thunb.) Harald. F. multiflora polysaccharide (FMP) was
      prepared and partially characterized by high performance liquid chromatography,
      fourier transform infrared spectrum and anion chromatography, and its antioxidant
      activities both in vitro and in vivo were investigated. FMP, with a molecular
      weight of 17,758Da consisted of glucose. In vivo, FMP had high hydroxyl radical
      scavenging activity and reducing capacity. In vivo, FMP increased serum
      superoxide dismutase and glutathione peroxidise activities and decreased the
      level of malondialdehyde. These results indicated that FMP exhibits high
      antioxidant activity both in vitro and in vivo and might retard human ageing
      associated with free radicals.

PMID- 29222012
TI  - Macrophage immunomodulatory activity of the polysaccharide isolated from Collybia
      radicata mushroom.
AB  - Polysaccharides from Collybia radicata mushroom (CRP) possess many functions,
      such as antiviral, anti-aging and hypolipidemic activities. However, little is
      known about their immunomodulatory activity. To address this issue, we did a
      thorough research into their immune effects on murine macrophages. The results
      showed that the 14942Da polysaccharide not only obviously improved the
      proliferation and phagocytosis of macrophages, but also induced the secretion of
      nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cytokines, such as
      tumor necrosis factor-alpha (TNF-alpha) and interleukin factors (IL-1beta, IL-6
      and IL-10). At a concentration of 850.0MUgmL-1, the polysaccharide stimulated
      their proliferation and phagocytosis to 2.1 and 3.4 times, respectively, as
      compared to the negative group. Meanwhile, it raised the production of NO by
      inducing iNOS in a concentration-dependent manner. Furthermore, it enhanced the
      release of these cytokines to multiples from 2.3 to 3.6 times. As an inhibitor of
      TLR4 (Toll-like Receptor 4), TAK242 suppressed the secretion of NO, iNOS and
      cytokines above 51%, and ORP acted on the cells mainly via TLR4. Consequently,
      the polysaccharide has a potent immunomodulatory activity by stimulating
      macrophages and can be considered as a novel potential immunopotentiator in
      medical and food industries.

PMID- 29222013
TI  - Purification, structural features and immunostimulatory activity of novel
      polysaccharides from Caulerpa lentillifera.
AB  - In this study, four purified fractions (CLGP1, CLGP2, CLGP3 and CLGP4) were
      prepared from green seaweed Caulerpa lentillifera. They were identified to be a
      novel kind of xylogalactomanans, differed in molecular weight, monosaccharide
      composition, and the content of uronic acids and sulfate groups, leading to
      various zeta-potential, ultrastructure and immunostimulatory activity.
      Especially, CLGP4 was quite different from the others, as it was found to be a
      homogeneous heteropolysaccharide composed of Xyl, Man and Gal in a percentage
      ratio of 1.00:2.15:2.40 with 3877.8kDa. Moreover, CLGP4 contained minor uronic
      acids (2.37%+/-0.94%) and the highest sulfate content (21.26%+/-1.22%). These
      differences in structural features had an effect on the zeta-potential and
      ultrastructure of CLGP4, showing rod-, rubble- and ellipsoid-shaped particles
      with largest negatively charge. In vitro immunostimulatory activity evaluation
      revealed that all the four fractions significantly stimulated macrophages, but
      CLGP4 showed more potent immunostimulatory activity due to its stronger function
      on promoting proliferation of macrophages, enhancing phagocytosis, NO production
      and acid phosphatase activity in macrophages. Therefore, CLGP4 could be explored
      as a natural immunomodulator. These results would help a fully exploition of
      Caulerpa lentillifera polysaccharides recognized as health-improving ingredients
      in functional foods.

PMID- 29222014
TI  - Preparation of purified fractions for polysaccharides from Monetaria moneta
      Linnaeus and comparison their characteristics and antioxidant activities.
AB  - The aim of this paper was to prepare purified fractions of polysaccharides from
      Monetaria moneta Linnaeus and further compare their characteristics and
      antioxidant activities. Firstly, three novel purified fractions, named MM-P1, MM
      P2 and MM-P3, were successfully prepared by a DEAE-Sepharose fast-flow column.
      Then, their characteristics were compared using chemical testing, FT-IR, GC and
      HPGPC. The results suggested that MM-P3 had higher molecular weights than MM-P1
      and MM-P2. MM-P1 was consisted of glucose, MM-P2 was consisted of glucose and
      xylose, and MM-P3 was comprised of glucose, xylose and mannose. Differed from MM
      P1 and MM-P2, MM-P3 had sulfuric radical and uronic acid groups. Finally, their
      antioxidant activities were also compared. We found that MM-P3 exhibited better
      antioxidant bioactivities than MM-P1 and MM-P2. The data demonstrated that three
      purified fractions derived from different adsorption capacity of DEAE-Sepharose
      fast-flow column possessed different structural characteristics and antioxidant
      activity.

PMID- 29222015
TI  - Synthesis and evaluation on pH- and temperature-responsive chitosan-p(MAA-co
      NIPAM) hydrogels.
AB  - In this study, chitosan-poly(methacrylic acid-co-N-isopropylacrylamide) [chitosan
      p(MAA-co-NIPAM)] hydrogels were synthesized by emulsion polymerization. In order
      to be used as a carrier for drug delivery systems, the hydrogels had to be
      biocompatible, biodegradable and multi-responsive. The polymerization was
      performed by copolymerize MAA and NIPAM with chitosan polymer to produce a
      chitosan-based hydrogel. Due to instability during synthesis and complexity of
      components to produce the hydrogel, further study at different times of reaction
      is important to observe the synthesis process, the effect of end product on
      swelling behaviour and the most important is to find the best way to control the
      hydrogel synthesis in order to have an optimal swelling behaviour for drug
      release application. Studied by using Fourier transform infra-red (FTIR)
      spectroscopy found that, the synthesized was successfully produced stable
      chitosan-based hydrogel with PNIPAM continuously covered the outer surface of
      hydrogel which influenced much on the stability during synthesis. The chitosan
      and PMAA increased the zeta potential of the hydrogel and the chitosan capable to
      control shrinkage above human body temperature. The chitosan-p(MAA-co-NIPAM)
      hydrogels also responses to pH and temperature thus improved the ability to
      performance as a drug carrier.

PMID- 29222016
TI  - The toxin BjussuLAAO-II induces oxidative stress and DNA damage, upregulates the
      inflammatory cytokine genes TNF and IL6, and downregulates the apoptotic-related
      genes BAX, BCL2 and RELA in human Caco-2 cells.
AB  - Colorectal carcinoma is one of the most common cancers in adults. As
      chemotherapy, the first-choice treatment for colorectal carcinoma, is often
      infeasible due to acquired tumor resistance and several adverse effects, it is
      important to discover and explore new molecules with better therapeutic action.
      Snake venom toxins have shown promising results with high cytotoxicity against
      tumor cells, but their mechanisms of action remain unclear. Here we examined how
      BjussuLAAO-II, an L-amino acid oxidase isolated from Bothrops jararacussu snake
      venom, exerts cytotoxicity towards colorectal adenocarcinoma human cells (Caco-2)
      and human umbilical vein endothelial cell line (HUVEC). A 24-h treatment with
      BjussuLAAO-II at 0.25 - 5.00 MUg/mL diminished cell viability by decreasing (i)
      mitochondrial activity, assessed by reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyl-2H-tetrazolium bromide and resazurin; (ii) the activity of acid
      phosphatases; and (iii) lysosomal function, assessed by neutral red uptake.
      BjussuLAAO-II also increased intracellular levels of reactive oxygen species and
      DNA damage, as assessed by fluorescence and the comet assay, respectively.
      BjussuLAAO-II altered the expression of cell proliferation-related genes, as
      determined by RT-qPCR: it elevated the expression of the inflammatory cytokine
      genes TNF and IL6, and lowered the expression of the apoptotic-related genes BAX,
      BCL2, and RELA. Therefore, BjussuLAAO-II induces Caco-2 cells death by acting on
      multiple intracellular targets, providing important data for further studies to
      assess whether these effects are seen in both tumor and normal cells, with the
      aim of selecting this drug for possible therapeutic purposes in the future.

PMID- 29222017
TI  - Increasing susceptibility to oxidative stress by cataract-causing crystallin
      mutations.
AB  - Cataract, a crystallin protein aggregation disease, is the leading cause of human
      blindness worldwide. Congenital cataract may be induced by many factors and
      genetic disorders accounts for about half of the cases. Inherited mutations can
      promote cataract formation by affecting crystallin structure, solubility,
      stability, protein interactions and aggregatory propensity. In this research, we
      investigated the potential role of oxidative damage in congenital cataracts
      caused by six mutations in gammaC- and gammaD-crystallins, the predominant
      structural proteins in the lens. H2O2 treatment induced structural changes for
      both the wild type and mutated proteins. Oxidization by H2O2 or UV light
      facilitated protein oligomerization and thermal aggregation. H2O2 treatment
      promoted thermal aggregation of all proteins. By increasing the susceptibility,
      cataract-causing mutations amplified the deleterious effects of oxidative damage.
      Our results suggested that oxidative damage might play an important role in the
      onset and/or progression of congenital cataract caused by both Cys and non-Cys
      substitutions.

PMID- 29222018
TI  - Physicochemical properties and biological activities of polysaccharides from
      Lycium barbarum prepared by fractional precipitation.
AB  - Traditional separation and purification process of Lycium barbarum
      polysaccharides (LBP) includes water extraction, alcohol precipitation,
      deproteinization and ion-exchange column chromatography, which is complicated and
      time-consuming. In our study, retentate LBP-I and dialysate LBP-O were obtained
      from LBP by water extraction, alcohol precipitation and deproteinization. LBP-I
      was separated by fractional precipitation and three fractions (LBP-I-1, LBP-I-2
      and LBP-I-3) were obtained. The three fractions were further purified by gel
      permeation chromatography to LBGP-I-1, LBGP-I-2 and LBGP-I-3 with yields of
      0.05%, 0.03%, and 0.19%, respectively, which are higher than yields by
      traditional method. The physicochemical properties, biological activities of LBGP
      I-1, LBGP-I-2 and LBGP-I-3 were investigated. The results indicated that LBGP-I-1
      (3.19 * 104 Da) consists of arabinose (21.95%), glucose (51.22%) and galactose
      (17.07%); LBGP-I-2 (2.92 * 104 Da) mainly consists of arabinose (19.35%), glucose
      (32.26%) and galactose (35.48%); LBGP-I-3 (9.12 * 104 Da) mainly consists of
      arabinose (48.15%) and galactose (44.44%). LBGP-I-1 and LBGP-I-2 were different
      from the components purified by traditional method. LBGP-I-3 could most
      significantly enhance macrophages NO, phagocytic capacity, and acid phosphatase.
      LBP-O exhibits the strongest anti-oxidant activities in vitro. These results
      provided a reference for applications of Lycium barbarum polysaccharides which
      would benefit the development of industry and agriculture.

PMID- 29222019
TI  - A novel use of cellulose based filter paper containing silver nanoparticles for
      its potential application as wound dressing agent.
AB  - The frequent use of antibiotics against microbial infections may lead to the
      emergence of antibiotic resistant microbial strains. To overcome these microbial
      strains, we need to fabricate alternative materials which can handle them. It is
      for this reason, we have fabricated cellulose (CE) based filter paper (FP)
      composite scaffolds comprising of adsorbed chitosan (CS) and sliver (Ag)
      nanoparticles (NPs). The AgNPs are incorporated in the CS layer of the composite
      scaffold. Prior to evaluate the efficacy of the scaffolds against gram positive
      and gram negative bacterial strains, the scaffolds were characterized for the
      presence of the Ag NPs with field emission scanning electron microscope (FE-SEM),
      fourier transform infrared (FTIR) spectroscopy and x-ray diffractometer (XRD).
      These techniques confirmed the presence of Ag NPs in the composite scaffold. The
      biocompatibility of the scaffolds was assessed by subjecting pristine FP, CS
      adsorbed FP (CS-FP) and Ag loaded CS-FP (Ag-CS-FP) composite scaffolds to in
      vitro studies. From the data obtained, it was observed that NIH3T3 fibroblastic
      cells adhered and proliferated onto all the scaffolds. Furthermore, the scaffolds
      exhibited good antibacterial activity against both strains of bacteria. It is,
      therefore, concluded that these scaffolds could find potential application in
      biomedical field, particularly as a wound dressing agent.

PMID- 29222020
TI  - Synthesis of protocatechuic acid grafted chitosan copolymer: Structure
      characterization and in vitro neuroprotective potential.
AB  - Excessive free radicals can cause oxidative damage to human tissues, which
      results in a variety of diseases. Therefore, the development of antioxidant
      materials is one of the great projects in biomedical field. In this work,
      antioxidant protocatechuic acid (PCA) monomers were grafted onto chitosan (CS)
      backbones to develop a PCA grafted chitosan (PCA-g-CS) antioxidant copolymer via
      the method of free radical-induced grafting reaction. The formation of covalent
      bonds between PCA and CS were confirmed by FTIR, 1H NMR, XRD and UV-vis. The
      antioxidant activity of PCA-g-CS was analyzed by 2, 2-diphenyl-1-picrylhydrazyl
      (DPPH) and hydroxyl radical scavenging assays. In addition, the cytotoxicity of
      PCA-g-CS on neuron-like rat phaeochromocytoma (PC12) cells was evaluated by using
      MTT assay. The neuroprotective effects against hydrogen peroxide (H2O2) and l
      glutamic acid (GLU) induced apoptosis in PC12 cells were also investigated. Our
      results demonstrated that the PCA-g-CS antioxidant copolymer had the ability to
      scavenge DPPH and hydroxyl radical in vitro. Furthermore, the PCA-g-CS was
      biocompatible and had neuroprotective effects against free radical-induced
      apoptosis in PC12 cells. This PCA-g-CS copolymer is firstly synthesized for
      neuroprotection and the results suggest the PCA-g-CS may be a potential
      antioxidant material in the treatment of oxidative damage related diseases.

PMID- 29222021
TI  - Identification and validation of salivary proteomic signatures for non-invasive
      detection of ovarian cancer.
AB  - Ovarian cancer (OC) is one of the most lethal cancers among all gynecological
      malignancies. An effective and non-invasive screening approach is needed urgently
      to reduce high mortality rate. The purpose of this study was to identify the
      salivary protein signatures (SPS) for non-invasive detection of ovarian cancer.
      Differentially expressed SPS were identified by fluorescence-based 2D-DIGE
      coupled with MALDI/TOF-MS. The expression levels of three differential proteins
      (Lipocalin-2, indoleamine-2, 3-dioxygenase1 (IDO1) and S100A8) were validated
      using western blotting and ELISA. Immunohistochemistry and qRT-PCR were performed
      in an independent cohort of ovarian tumor tissues. 25 over expressed and 19 under
      expressed (p<0.05) proteins between healthy controls and cancer patients were
      identified. Lipocalin-2, IDO1 and S100A8 were selected for initial verification
      and successfully verified by immunoassay. Diagnostic potential of the candidate
      biomarkers was evaluated by ROC analysis. The selected biomarkers were further
      validated by immunohistochemistry in an independent cohort of ovarian tissues.
      The global expression of selected targets was also analyzed by microarray and
      validated using qRT-PCR to strengthen our hypothesis. Tumor secreted proteins
      identified by 'dual-omics' strategy, whose concentration are significantly high
      in ovarian cancer patients have obvious potential to be used as screening
      biomarker after large scale validation.

PMID- 29222022
TI  - Do Resident Case Logs Meet ACGME Requirements? A Comparison Between Acute Care
      and Elective Cases.
AB  - PURPOSE: Operative experience is at the core of general surgery residency, and
      recently operative volume requirements for graduating residents were increased.
      The ACGME has outlined 4 areas of required resident participation and
      documentation in order for a surgical case to be logged: determination or
      confirmation of the diagnosis, provision of preoperative care, selection and
      accomplishment of the operative procedure, and direction of the postoperative
      care. The purpose of this study was to examine whether general surgery residents
      are currently meeting the required care participation documentation standard and
      to examine the effect of acute care vs. elective cases on documentation. METHODS:
      The operative case logs of 7 PGY-3 and 7 PGY-5 general surgery residents from
      March 2016 were retrospectively reviewed and compared to the electronic medical
      record (EMR) to verify documentation of resident participation in each of the 4
      required areas. Chart review was also utilized to classify cases as either acute
      care or elective. RESULTS: A total of 339 cases were reviewed (159 PGY-3 and 180
      PGY-5). Of these, 251 cases were classified as elective and 88 were classified as
      acute care. Overall, documentation of comprehensive care (participation in all
      four required areas) was found for 44% of cases, with residents reporting
      participation in a higher percentage of comprehensive care (all 4 domains
      completed) than was actually documented in the EMR (71.9% vs. 44.4%, t[13] =
      2.57, p = 0.023, d = 1.13). Comprehensive care was documented more frequently in
      elective cases than acute care cases (49.7% vs. 38.3%), and there was less
      discrepancy between perceived and documented comprehensive care within elective
      cases (67% vs. 49.7%, t[13] = 1.17, p = 0.27) than acute care cases (80.9% vs.
      38.3%, t[13] = 4.40, p = 0.001). CONCLUSIONS: Despite ACGME requirements, the
      majority of cases logged by general surgery residents do not have documentation
      by the operating resident in the EMR verifying provision of comprehensive care.
      Elective cases were more likely to meet documentation requirements than acute
      care cases, and we purport that this is possibly secondary to restricted work
      hours. We expect that other programs would find similar compliance in the
      documentation of comprehensive care. These results question whether the
      requirement for documenting comprehensive care to log a surgical case is
      practical in surgical residency training, particularly with an increasing demand
      for operative volume in the setting of limited work hours.

PMID- 29222024
TI  - Continuous and not continuous 2-week treadmill training enhances the performance
      in the passive avoidance test in ischemic gerbils.
AB  - This study aims to investigate the frequency and total duration effects of the 2
      week treadmill training after experimental ischemic stroke in the passive
      avoidance test. We performed bilateral occlusion of common external carotid
      arteries, for five minutes, in Mongolian gerbils. The training groups were:
      continuous training for twelve consecutive days or not continuous training for
      six non-consecutive days. The groups remained in the treadmill for 15min, with
      the speed set at 10m/min, and the training started 24h after the stroke. In the
      Shuttle Box, each animal had ten trials during the Learning Session (LS), which
      occurred 24h before the stroke. The Retention Test (RT) occurred 24h after the
      stroke and started on the second, third, seventh and twelfth day after LS. After
      the experiments, the brains were perfused, and coronal sections of the CA1 area
      of the hippocampus were cut and stained with hematoxylin and eosin. ANOVA on
      Ranks was used for Behavioral data analysis and morphological data by percentage.
      Ischemic training groups showed preservation in neuron density in the CA1 area of
      the hippocampus, when compared to the control groups. Animals subjected to
      continuous training, showed a higher latency in the RT when compared to ischemic
      animals in both weeks [(2nd, H=39.81; P<0.05), (3rd, H=38.08; P<0.05), (7th,
      H=44.17; P<0.05), and (12th, H=39.55; P<0.05). Animals in the not continuous
      training showed higher latency in the RT, in the second week only [(2nd, H=39.81;
      P<0.05), (3rd, H=38.08; P<0.05), (7th, H=44.17; P<0.05), and (12th, H=39.55;
      P<0.05). These findings suggest that improvement of memory after stroke after
      treadmill training is dependent on the frequency and total duration of training.

PMID- 29222025
TI  - Preparation and comparison of tacrolimus-loaded solid dispersion and self
      microemulsifying drug delivery system by in vitro/in vivo evaluation.
AB  - This study aimed to compare the dissolution and the intestinal absorption of
      tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid
      dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent
      evaporation method and the freeze drying method. Hydroxypropyl methylcellulose
      (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum
      drying method. The formation of SD was confirmed by SEM images which showed new
      solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant
      (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion
      formed by the SMEDDS upon aqueous media had spherical droplets with a
      hydrodynamic size of 46.0+/-3.2nm. The dissolution of tacrolimus from SD and
      SMEDDS was performed in sink and non-sink conditions with various pH. As revealed
      by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in
      the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that
      both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus
      while the SMEDDS exhibited lower absorption rate constant (Ka) and apparent
      permeability coefficients (Papp) than the SD. The self-prepared SD with poloxamer
      188 or HPMC had comparable intestinal absorption as compared with Prograf(r). The
      tacrolimus-loaded SMEDDS and SD would be further compared by in vivo
      pharmacokinetic study.

PMID- 29222023
TI  - Regional brain gray matter changes in adolescents with single ventricle heart
      disease.
AB  - Adolescents with single ventricle heart disease (SVHD) show autonomic, mood, and
      cognitive deficits, indicating aberrations in brain areas that regulate these
      functions. However, the gray matter integrity in autonomic, mood, and cognitive
      control sites is unclear. We examined regional brain gray matter changes, using
      high-resolution T1-weighted images (3.0-T magnetic resonance scanner) with voxel
      based morphometry procedures, as well as mood and cognitive functions in SVHD
      (n=18; age, 15.7+/-1.1years; male, 10) and controls (n=31; age, 16.0+/-1.1years;
      male, 17). High-resolution T1-weighted images were realigned, gray matter tissue
      type partitioned, normalized to a common space, smoothed, and compared between
      groups (analysis of covariance; covariates, age and gender). The mood and
      cognitive scores were compared between groups using independent samples t-tests.
      SVHD subjects showed significantly altered mood and cognitive functions over
      controls. Significantly reduced gray matter emerged in multiple brain areas,
      including the thalamus, caudate nuclei, putamen, insula, prefrontal, post-central
      and precentral gyrus, occipital gyrus, para-hippocampal gyrus, temporal gyrus,
      and cerebellar sites in SVHD over controls. SVHD subjects show compromised gray
      matter integrity in autonomic, mood and cognitive control sites. The findings
      indicate that frequent deficits found in SVHD subjects have a brain structural
      basis in the condition.

PMID- 29222026
TI  - Transcriptome analysis provides insights into the immune responsive pathways and
      genes in the head kidney of tiger grouper (Epinephelus fuscoguttatus) fed with
      Spatholobus suberectus, Phellodendron amurense, or Eclipta prostrata.
AB  - The tiger grouper, Epinephelus fuscoguttatus, is an economically important fish
      in Southeast Asia but has been plagued by several diseases. Spatholobus
      suberectus (S), Phellodendron amurense (P), and Eclipta prostrate (E) are three
      commonly used Chinese medicinal herbs. Although previous pharmacological and
      clinical studies indicated that S, P, and E possess a variety of beneficial
      functions in mammals, little is known about their functions in farmed fish and
      the underlying molecular mechanism of their actions. Challenge tests in this
      study showed that after 14 days of diet supplement, all these herbs could
      effectively enhance the disease resistance of E. fuscoguttatus against Vibrio
      harveyi. However, the non-specific immune parameters of the herb-supplemented
      groups were not significantly different from the control group. To further
      explore the molecular mechanism of herbal immune-regulating effects on E.
      fuscoguttatus, transcriptome sequencing and RNA-Seq technique were applied on E.
      fuscoguttatus kidney. De novo transcriptome assembly of E. fuscoguttatus kidney
      yield 80,014 unigenes, among which, 44,901 (56.12%) were annotated with at least
      one of the public databases (Nr, Nt, Swiss-Prot, KEGG, COG, GO). Among these,
      22,738, 11,700 and 27,457 unigenes were assigned to 57, 25 and 258 categories of
      GO, COG and KEGG databases, respectively. Using Solexa/Illumina's DGE platform, a
      total of 231, 186 and 144 putative differentially expressed genes (DEGs) were
      detected in P, E and S group compared with the control group. GO analysis
      indicated that in P and E, down-regulated DEGs were dominant in almost every GO
      term; whereas in S, up-regulated DEGs were more dominant. KEGG pathway analysis
      revealed that putative DEGs in all three herb groups were obviously enriched in
      the pathways related to infective diseases and immune system. We also identified
      a number of immune relative genes and pathways (TLR5, IL8 and MAPK pathway, for
      instance) associated with P, E and S's regulatory effects on E. fuscoguttatus.
      This study will enrich the E. fuscoguttatus transcriptome database, contribute to
      a better understanding of the molecular mechanisms associated with the
      immunoregulatory activities of Chinese medicinal herbs on teleost and provide
      valuable information on the prevention of grouper Vibrio diseases using Chinese
      medicinal herbs.

PMID- 29222027
TI  - TBK1 from orange-spotted grouper exerts antiviral activity against fish viruses
      and regulates interferon response.
AB  - TANK-binding kinase-1 (TBK1) has been well studied in mammals because of its
      importance in type I interferon induction in antiviral immunity. However, the
      roles of fish TBK1 in virus infection still remained largely uncertain. In the
      current study, a TBK1 homolog from orange-spotted grouper (Epinephelus coioides)
      (EcTBK1) was cloned and its roles in fish viral infections were investigated.
      Sequence analysis showed that EcTBK1 encoded a 723-amino acid peptide which
      shared 98% and 73% identity to large yellow croaker (Larimichthys crocea) and
      human (homo sapiens), respectively. Multiple sequence alignments indicated that
      EcTBK1 contained conserved domains, including N-terminal kinase domain (KD), the
      middle ubiquitin-like domain (ULD) and C-terminal coiled-coil (CC) domains. The
      tissue distribution profiles demonstrated that EcTBK1 gene was constitutively
      expressed in all examined tissues, with predominant expression in intestine.
      Temporal expression analysis in vitro showed that the expression levels of EcTBK1
      were significantly up-regulated in response to both red-spotted grouper nervous
      necrosis virus (RGNNV) and Singapore grouper iridovirus (SGIV) infection,
      suggested that EcTBK1 might exert crucial roles in fish virus infection.
      Subcellular localization indicated that EcTBK1 expression was primarily in the
      cytoplasm in GS cells. The ectopic expression of EcTBK1 significantly inhibited
      both SGIV and RGNNV replication. Furthermore, EcTBK1 overexpression significantly
      increased the expression levels of interferon related cytokines and pro
      inflammatory factors. In addition, the overexpression of EcTBK1 increased the
      IRF3- and IRF7-regulated interferon promoter ISRE and IFN activity, and the
      regulatory effect on interferon immune response were dependent on its kinase
      domain. Together, we speculated that grouper TBK1 exerted antiviral activity
      against iridovirus and nodavirus via regulating the interferon immune and
      inflammatory response.

PMID- 29222028
TI  - Sodium butyrate enhanced physical barrier function referring to Nrf2, JNK and
      MLCK signaling pathways in the intestine of young grass carp (Ctenopharyngodon
      idella).
AB  - This study evaluated the effect of dietary sodium butyrate (SB) supplementation
      on the intestinal physical barrier function of young grass carp (Ctenopharyngodon
      idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg-1
      diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets:
      0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg-1 diet for 60 days.
      Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila
      to explore the effect of SB supplementation on intestinal physical barrier
      function and the potential mechanisms in fish. The results showed that optimal SB
      supplementation: (1) down-regulated the cysteine-aspartic protease-2 (caspase-2),
      caspase-3 (rather than PI), caspase-7, caspase-8 (rather than PI), caspase-9,
      fatty acid synthetase ligand (FasL), apoptotic protease activating factor-1 (Apaf
      1), B-cell lymphoma 2 associated X protein (Bax) and c-Jun Nterminal protein
      kinase (JNK) mRNA levels, up-regulated the B-cell lymphoma protein-2 (Bcl-2)
      (rather than PI), inhibitor of apoptosis proteins (IAP) and myeloid cell leukemia
      1 (Mcl-1) mRNA levels in the intestine (P < 0.05), inhibited the intestinal cell
      apoptosis, maintained the intestine cell structure integrity; (2) increased NF-E2
      related factor 2 (Nrf2) mRNA levels and nucleus protein levels, and down
      regulated kelch-like-ECH-associated protein (Keap1b) (rather than Keap1a) mRNA
      levels in the intestine, up-regulated copper/zinc superoxide dismutase (CuZnSOD),
      manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase 1a
      (GPx1a), GPx1b, GPx4a, GPx4b, glutathione S-transferases R (GSTR), GSTP1, GSTP2,
      GSTO1, GSTO2 and glutathione reductase (GR) mRNA levels in the intestine,
      increased the corresponding antioxidant enzymes activity (P < 0.05), thus
      enhancing the ability of scavenging free radicals and decreasing the reactive
      oxygen species (ROS) content, decreasing the lipid and protein peroxidation, as
      well as alleviating oxidative damage; (3) down-regulated the molecule myosin
      light-chain kinase (MLCK) mRNA levels in the intestine, and up-regulated the
      occludin, zonula occludens-1 (ZO-1), ZO-2, claudin-b, claudin-c, claudin-f,
      claudin-3c (rather than PI), claudin-7a, claudin-7b and claudin-11 mRNA levels,
      down-regulated claudin-12, claudin-15a and claudin-15b mRNA levels (P < 0.05),
      thus maintaining the structural integrity between cells. This study suggests that
      SB supplementation could improve fish intestinal physical barrier function.
      Furthermore, according to the positive effect, MSB was superior to PSB on
      improving intestinal physical barrier function of fish. Finally, based on protein
      carbonyl content in the PI, the optimal SB supplementation (MSB as SB source) for
      young grass carp was estimated to be 338.8 mg kg-1 diet.

PMID- 29222029
TI  - Rapid regulation of substrate use for oxidative phosphorylation during a single
      session of high intensity interval or aerobic exercises in different rat skeletal
      muscles.
AB  - Different exercise protocols lead to long-term adaptations that are related to
      increased mitochondrial content through the activation of mitochondrial
      biogenesis. However, immediate mitochondrial response to exercise and energetic
      substrate utilization is still unknown. We evaluate the mitochondrial physiology
      of two types rat skeletal muscle fibres immediately after a single session of
      high intensity interval exercise (HIIE) or aerobic exercise (AER). We found AER
      was able to reduce the ATP synthesis dependent oxygen flux in the tibialis (TA)
      when stimulated by complex I and II substrates. On the other hand, there was an
      increase of the maximum velocity (Vmax) for glycerol-phosphate oxidation and Vmax
      and affinity (KM) of palmitoyl-carnitine oxidation (PC). The exercise did not
      affect oxygen flux coupled to ATP synthesis in red gastrocnemius (RG) but,
      surprisingly, reduced its affinity for PC, decreasing the apparent catalytic
      efficiency (Vmax/KM) of oxidation for PC. Neither exercise protocol was able to
      change the electron transfer system capacity of the mitochondria or markers of
      mitochondrial content. The AER group had increased H2O2 production compared to
      the SED and HIIE groups, with the mechanism being predominantly the escape of
      electrons through reverse flux in complex I and other sites in TA, and only
      through other sites in RG. There were no changes in the activities of antioxidant
      enzymes. Our results show that mitochondria from different muscles submitted to
      distinct exercise protocols show alterations in the specific fluxes of substrate
      utilization and oxygen metabolism, indicating that the dynamics of mitochondria
      are linked to the metabolic flexibility.

PMID- 29222030
TI  - Regional ventilation distribution and dead space in anaesthetized horses treated
      with and without continuous positive airway pressure: novel insights by
      electrical impedance tomography and volumetric capnography.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of continuous
      positive airway pressure (CPAP) on regional distribution of ventilation and dead
      space in anaesthetized horses. STUDY DESIGN: Randomized, experimental, crossover
      study. ANIMALS: A total of eight healthy adult horses. METHODS: Horses were
      anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous
      infusion in dorsal recumbency, and administered in random order either CPAP (8
      cmH2O) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric
      capnography (VCap) measurements were performed every 30 minutes. Lung regions
      with little ventilation [dependent silent spaces (DSSs) and nondependent silent
      spaces (NSSs)], centre of ventilation (CoV) and dead space variables, as well as
      venous admixture were calculated. Statistical analysis was performed using
      multivariate analysis of variance and Pearson correlation. RESULTS: Data from six
      horses were statistically analysed. In CPAP, the CoV shifted to dependent parts
      of the lungs (p < 0.001) and DSSs were significantly smaller (p < 0.001), while
      no difference was seen in NSSs. Venous admixture was significantly correlated
      with DSS with the treatment time taken as covariate (p < 0.0001; r = 0.65). No
      differences were found for any VCap parameters. CONCLUSIONS AND CLINICAL
      RELEVANCE: In dorsally recumbent anaesthetized horses, CPAP of 8 cmH2O results in
      redistribution of ventilation towards the dependent lung regions, thereby
      improving ventilation-perfusion matching. This improvement was not associated
      with an increase in dead space indicative for a lack in distension of the airways
      or impairment of alveolar perfusion.

PMID- 29222031
TI  - Evaluation of the effect of mesotherapy in the management of back pain in police
      working dog.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of mesotherapy in dogs
      compared with a positive control group. STUDY DESIGN: Experimental, randomized,
      blinded study. ANIMALS: Fifteen working police dogs with chronic back pain.
      METHODS: Animals were divided randomly into control (CG; n = 5) and treatment
      groups (TG; n = 10). A combination of 140 mg lidocaine, 15 mg dexamethasone and
      20 mg thiocolchicoside was administered to group TG along with a 70-day course of
      a placebo, administered as if it was carprofen. Carprofen was administered to
      Group CG for 70 days, at a dose adjusted to their weight. On day 0, an
      intradermal injection of Ringer's lactate was also administered. Both groups were
      rested for 3 days and resumed normal activity over a 5-day period. Response to
      treatment, measured by the Canine Brief Pain Inventory (CBPI) and the Hudson
      Visual Analogue Scale (HVAS), was evaluated before treatment (T0), after 15 days
      (T1) and 1 (T2), 2 (T3), 3 (T4), 4 (T5) and 5 (T6) months. Results were compared
      using a Mann-Whitney test or a paired samples t test. RESULTS: When comparing
      CBPI results, no differences were found between groups TG and CG at T0 through T3
      and in T6 and T7. Differences were observed in CBPI sections after the
      discontinuation of carprofen: at T4 [p = 0.02 for Pain Interference Score (PIS)
      and p = 0.03 for Pain Severity Score (PSS)] and T5 (p = 0.16 for PIS and p = 0.03
      for PSS), with group TG having overall better results. Individual treatment
      results were considered successful in one dog of group CG (20%), whereas in group
      TG, success was higher (ranging from 78% at T1 to 22% at T7). No significant
      differences were registered with the HVAS. CONCLUSIONS AND CLINICAL RELEVANCE:
      Mesotherapy may be a promising treatment option for canine musculoskeletal
      related pain. Further studies are required.

PMID- 29222032
TI  - Assessment of the laxative activity of an ethanolic extract of Bambusa
      arundinacea (Retz.) Willd. shoot.
AB  - ETHNOBOTANICAL RELEVANCE: Bambusa arundinacea (Retz.) Willd., commonly known as
      Kanta Bans, plays an important ethnobotanical role, especially in Asia. In
      traditional medicine it has reportedly been used for the treatment of
      constipation, blood-diseases, leucodema, inflammation and urinary discharges. A
      number of ethnomedicinal records exist regarding the use of B. arundinaceae
      shoots as a laxative, however, there are no scientific studies reported on its
      laxative activity. Therefore, the aim of this present study was to evaluate the
      laxative activity of an ethanolic B. arundinaceae shoot extract in mice.
      MATERIALS AND METHODS: B. arundinacea shoots were collected from Dhaka,
      Bangladesh in July 2015. An ethanolic shoot extract was obtained and its laxative
      activity was evaluated by faecal consistency, gastrointestinal transit and entero
      pooling assays in a mouse model. Furthermore, a phytochemical investigation of
      the extract was conducted by UHPLC-ESI-QqQ MS and UHPLC-ESI-Orbitrap MS analysis.
      RESULTS: The ethanolic shoot extract of B. arundinacea showed significant
      laxative activity in our mouse model, with significant increases in (i) the
      amount of wet faeces, with the maximum effect at 2h for 500mg/kg (47.92%), (ii)
      gastrointestinal transit (67.18% and 60.03% for doses of 250 and 500mg/kg,
      respectively), and (iii) small intestine content at the test doses of 250 and
      500mg/kg p.o. Phytochemical investigation identified a total of thirty compounds
      in the ethanolic shoot extract of B. arundinacea using UHPLC-ESI-QqQ MS and UHPLC
      ESI-Orbitrap MS analysis. CONCLUSIONS: The results of this study provide support
      for the traditional use of B. arundinacea shoot as a laxative.

PMID- 29222033
TI  - Multiple perspectives of qingkailing injection-fraction-single compound in
      revealing the hepatotoxicity of baicalin and hyodeoxycholic acid.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The complexity of ingredients in traditional
      Chinese medical formulas and the limited consideration of toxicological responses
      are fundamental issues that hamper prognostic information of drug quality
      control. MATERIALS AND METHODS: A multidisciplinary approach for quality control
      of Qingkailing injection (QKL) regarding drug induced liver toxicity was
      described for the first time. High content image analysis (HCA) was combined with
      reverse-phase chromatographic separation and high-resolution MS detection
      technologies to provide the dynamic responses of drug induced HepG2 cell injury.
      Firstly, a simple and rapid method for simultaneous qualification and
      quantification of 21 major constituents in QKL was established and validated
      using ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap
      mass spectrometer (UHPLC-Q-Orbitrap), which were operated in full MS/dd-MS2 mode
      and thus simultaneously acquired quantitative high resolution (HR) full scan data
      and confirmatory HR MS2 data. Secondly, repeated semi-preparation HPLC was
      applied to obtain four fractions (F1-F4) for HCS analysis. Finally, potential
      hepatotoxicity was determined by five hepatotoxicity biomarkers, including cell
      loss, DNA condense, glutathione (GSH) depletion, reactive oxygen species (ROS)
      formation, and mitochondria membrane potential (MMP) depolarization. RESULTS: The
      detection in polarity switching mode empowered the coverage of comprehensive
      constituents with different chemical properties. Satisfactory linearity
      precisions, repeatability, stability, and recovery were achieved. QKL injection
      significantly induced HepG2 cell injury above the concentration of 1.25% (v/v).
      Meanwhile, flavone glycosides (F3) and stinasterols (F4) fractions exhibited
      hepatotoxicity above 75MUg/mL and 50MUg/mL, respectively. Still further, baicalin
      originated from F3 significantly caused cell loss and glutathione (GSH)
      depletion. In parallel, hyodeoxycholic acid from F4 induced cell loss, nucleus
      condense, and GSH reduction as well. CONCLUSIONS: Our work provides multiple
      perspectives based on injection-fractions-single compound format to improve QKL
      pharmacovigilance through revealing the potential hepatotoxic material basis.
      Additionally, our study provides an integrating paradigm for the comprehensive
      and systematic quality control of traditional Chinese medical formulas.

PMID- 29222034
TI  - Management of invasive candidiasis and candidaemia in critically ill adults:
      expert opinion of the European Society of Anaesthesia Intensive Care Scientific
      Subcommittee.
AB  - OBJECTIVE: The global burden of invasive fungal disease is increasing. Candida
      albicans remains the leading cause of fungal bloodstream infections, although non
      albicans candidal infections are emerging. Areas of controversy regarding
      diagnosis and management are hampering our ability to respond effectively to this
      evolving threat. The purpose of this narrative review is to address current
      controversies and provide recommendations to supplement guidelines. DIAGNOSIS OF
      INVASIVE CANDIDIASIS: Diagnosis of invasive candidiasis requires a combination of
      diagnostic tests and patient risk factors. Beta-D glucan and Candida albicans
      germ tube antibody are both used as biomarkers as adjuncts to diagnosis, although
      direct culture remains the gold standard. Scoring systems are available to help
      distinguish between colonization and invasive disease. TREATMENT OF INVASIVE
      CANDIDIASIS: Echinocandins are recommended as first-line therapy in candidaemia,
      with de-escalation to fluconazole when clinical stability is achieved. Empirical
      therapy is highly recommended in high-risk patients, but a more targeted pre
      emptive approach is now being favoured. The evidence for prophylactic therapy
      remains weak. SUMMARY: Mortality attributable to invasive candidiasis may be as
      high as 70%. Prompt diagnosis and treatment, in conjunction with source control,
      are the key to improving outcomes.

PMID- 29222036
TI  - Central and peripheral line-associated bloodstream infections in Australian
      neonatal and paediatric intensive care units: findings from a comprehensive
      Victorian surveillance network, 2008-2016.
AB  - BACKGROUND: Healthcare-associated infections in neonatal and paediatric
      populations are associated with poorer outcomes and healthcare costs, and
      surveillance is a necessary component of prevention programmes. AIM: To evaluate
      burden of illness, aetiology, and time-trends for central and peripheral line
      associated bloodstream infection (CLABSI and PLABSI) in Australian neonatal and
      paediatric intensive care units (ICUs) between July 1st, 2008 and December 31st,
      2016. METHODS: Using National Healthcare Safety Network methods, surveillance in
      neonatal and paediatric units was performed by hospitals participating in the
      Victorian Healthcare Associated Infection Surveillance System. Mixed effects
      Poisson regression was used to model infections over time. FINDINGS: Overall, 82
      paediatric CLABSI events were reported during 37,125 CVC-days (2.21 per 1000 CVC
      days), 203 neonatal CLABSI events were reported during 92,169 CVC-days (2.20 per
      1000 CVC-days), and 95 neonatal PLABSI events were reported during 142,240
      peripheral line-days (0.67 per 1000 peripheral line-days). Over time, a
      significant decrease in quarterly risk for neonatal CLABSI events was observed
      (risk ratio (RR): 0.98; 95% confidence interval: 0.97-0.99; P = 0.023) and this
      reduction was significant for the 751-1000 g birth weight cohort (RR: 0.97; P =
      0.015). Most frequently, coagulase-negative Staphylococcus spp. (24.2%) and
      Staphylococcus aureus (16.1%) were responsible for CLABSI events. A significant
      reduction in Gram-negative neonatal infections was observed (annual RR: 0.85; P <
      0.001). CONCLUSION: CLABSI rates in neonatal and paediatric ICUs in our region
      are low, and neonatal infections have significantly diminished over time.
      Evaluation of infection prevention programmes is required to determine whether
      specific strategies can be implemented to further reduce infection risk.

PMID- 29222035
TI  - Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE
      study.
AB  - BACKGROUND: Currently, contact precautions are recommended for patients colonized
      or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBL-PE). Recent studies have challenged this strategy. This study aimed to
      assess the rate of ESBL-PE faecal carriage among hospitalized patients according
      to type of hospital ward, and to identify risk factors associated with carriage.
      METHODS: A point prevalence study was conducted in five different types of
      hospital ward [medical, surgical, intensive care unit (ICU), after care and
      rehabilitation, and geriatric] in eight French hospitals. All patients included
      in the study provided a fresh stool sample. RESULTS: In total, 554 patients were
      included in the study, with a median age of 73 years (range 60-82 years). The
      overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently
      encountered species among ESBL-PE was Escherichia coli (71.4%), followed by
      Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal
      carriage on univariate analysis were: living in the Paris region (P<0.01) and
      hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative
      duration of hospital stay before screening was not associated with a
      significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The
      ESBL-PE colonization rate was much higher for patients hospitalized on geriatric
      wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on
      surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation
      (11.2%). CONCLUSION: The overall prevalence of ESBL-PE faecal carriage was 17.7%,
      with only 21% of patients identified previously as carriers. The delay between
      admission and screening was not associated with an increase in ESBL-PE faecal
      carriage.

PMID- 29222037
TI  - Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial
      mesenchymal-transition and stem cell properties in pancreatic ductal epithelial
      cells.
AB  - Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to
      develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal
      malignancies. Cancer stem cells (CSC) are essential for initiation and
      maintenance of tumors, and acquisition of CSC-features is linked to epithelial
      mesenchymal-transition (EMT). The present study investigated whether
      hyperglycemia promotes EMT and CSC-features in premalignant and malignant
      pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose),
      Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal
      phenotype along with pronounced colony formation. While hyperglycemia (25 mM d
      glucose) did not impact the mesenchymal phenotype of Panc1 cells, CSC-properties
      were aggravated exemplified by increased Nanog expression and Nanog-dependent
      formation of holo- and meroclones. In H6c7-kras cells, high glucose increased
      secretion of Transforming-Growth-Factor-beta1 (TGF-beta1) as well as TGF-beta1
      signaling, and in a TGF-beta1-dependent manner reduced E-cadherin expression,
      increased Nestin expression and number of meroclones. Finally, reduced E-cadherin
      expression was detected in pancreatic ducts of hyperglycemic but not
      normoglycemic mice. These data suggest that hyperglycemia promotes the
      acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-beta
      signaling and might explain how T2DM facilitates pancreatic tumorigenesis.

PMID- 29222038
TI  - HDAC6 inhibition induces glioma stem cells differentiation and enhances cellular
      radiation sensitivity through the SHH/Gli1 signaling pathway.
AB  - The existence of small numbers of stem-like cells, called glioma stem cells
      (GSCs), in human glioblastoma multiforme (GBM) is responsible for recurrence due
      to resistance to radiotherapy and chemotherapy. Inhibition of histone deacetylase
      6 (HDAC6) enhanced radiosensitivity of cancer cells. However, the effect of
      inhibiting HDAC6 on stemness and radioresistance of GSCs and its molecular
      mechanism are largely unknown. In the present study, we found that HDAC6 was
      upregulated in GSCs comparing to non-stem tumor cells. Inhibiting HDAC6
      downregulated glioma-associated oncogene homolog 1 (Gli1), Patched (Ptch1 and
      Ptch2) receptors, components of SHH signal, expression and activity in GSCs.
      Restraining HDAC6 decreased cell proliferation, induces differentiation and
      increased apoptosis of GSCs via inactivation of SHH/Gli1 signaling pathway.
      Moreover, HDAC6 inhibition decreased DNA damage repair capacity of GSCs through
      degradation of checkpoint kinase (CHK) 1 caused by X-linked inhibitor of
      apoptosis (XIAP) downregulation, leading to elevated radiosensitivity. Taken
      together, these findings indicate that HDAC6 inhibition decreased stemness of
      GSCs and enhanced GSCs radiosensitivity through inactivating SHH/Gli1 pathway.
      This provides a promising novel drug target to overcome GSCs stemness and
      radioresistance.

PMID- 29222040
TI  - Prohibitin: A new player in immunometabolism and in linking obesity and
      inflammation with cancer.
AB  - Immunometabolism, which has important implications in cancer biology, has emerged
      as a major regulator of different immune cell types. Various factors that
      integrate metabolic switches within immune cells with signal directed program
      that promote or inhibit their functions remain largely unidentified. Furthermore,
      sex differences are known to exist in immune functions and cancer incidences in
      the body and sex steroid hormones are integral component of these differences.
      However, factors that mediate such differences, and the potential link between
      the two fundamental aspects of immune cell biology that contributes to sex
      differences in health and disease remain unexplored. New evidence derived from
      novel tissue-specific transgenic mouse models of prohibitin (PHB) has revealed
      its crucial role in sex differences in adipocyte and macrophage functions and a
      potential role in endocrine-immune crosstalk. This review provides a point of
      view on the emerging role of PHB in immune functions with special focus on
      immunometabolism and on the immunomodulatory effects of sex steroids. We propose
      that PHB plays a crucial role in integrating cell signaling events with metabolic
      switches, and may serve as a potential target for cancer immunotherapeutic.

PMID- 29222041
TI  - TAp73 inhibits cell invasion and migration by directly activating KAI1 expression
      in colorectal carcinoma.
AB  - p73 is a member of the p53 family of transcription factors and, like p53, plays a
      role as a tumor suppressor. p73 is involved in development, proliferation,
      apoptosis and metastasis. However, the precise molecular mechanisms underlying
      its function in inhibiting metastasis remain largely unknown. Here, we show that
      induction of TAp73 decreased invasion and migration activity of colorectal cancer
      cells, whereas knockdown of TAp73 led to increased invasion and migration
      activity. KAI1 was identified as a transcriptional target of TAp73 and its
      expression is indispensable for TAp73-mediated inhibition of cell invasion and
      migration. Furthermore, induction of TAp73 in colorectal cancer cells elevated
      KAI1 expression and decreased the frequency of hepatic metastasis in vivo.
      Whereas, the decreased invasion and migration activities caused by TAp73
      induction were abrogated by knockdown of KAI1. Interestingly, TAp73 and KAI1 are
      overexpressed in primary colorectal cancers and a significant correlation between
      TAp73 and KAI1 expression was detected, but their expressions were significantly
      down-regulated in metastatic cancers. Taken together, our results support a novel
      role for TAp73 in controlling colorectal cancer cell invasion, migration and
      metastasis by regulating transcription of KAI1.

PMID- 29222042
TI  - Antiangiogenic compounds: well-established drugs versus emerging natural
      molecules.
AB  - Angiogenesis is the natural and physiologic process of growing blood vessels from
      pre-existing ones. Pathological angiogenesis occurs when the precise balance of
      all the molecular pathways that regulate angiogenesis is disrupted, and this
      process is a critical step in many diseases, including cancer. A limited number
      of antiangiogenic synthetic drugs have been developed. However, due to toxicity
      and side effects issues, the search for alternative to existing drugs is ongoing.
      In this sense, natural molecules obtained from plants or macrofungi, have
      demonstrated extraordinary potential in the treatment of angiogenesis-related
      pathologies, specially taking into consideration its absence or very low
      toxicity, when compared to synthetic drugs. Using natural compounds as potential
      angiogenesis modulators is thus a promising field of research, supporting the
      creation of novel therapies able to reduce the use of drugs and associated side
      effects. In this review, the current status of antiangiogenic drugs and the wide
      variety of natural extracts and molecules with antiangiogenic capacities, as well
      as the angiogenesis molecular pathways and therapeutic targets, are presented.
      Finally, the challenges that need to be overcome in order to increase the use of
      natural compounds for clinical purposes are discussed.

PMID- 29222039
TI  - The role of STAT3 in leading the crosstalk between human cancers and the immune
      system.
AB  - The development and progression of human cancers are continuously and dynamically
      regulated by intrinsic and extrinsic factors. As a converging point of multiple
      oncogenic pathways, signal transducer and activator of transcription 3 (STAT3) is
      constitutively activated both in tumor cells and tumor-infiltrated immune cells.
      Activated STAT3 persistently triggers tumor progression through direct regulation
      of oncogenic gene expression. Apart from its oncogenic role in regulating gene
      expression in tumor cells, STAT3 also paves the way for human cancer growth
      through immunosuppression. Activated STAT3 in immune cells results in inhibition
      of immune mediators and promotion of immunosuppressive factors. Therefore, STAT3
      modulates the interaction between tumor cells and host immunity. Accumulating
      evidence suggests that targeting STAT3 may enhance anti-cancer immune responses
      and rescue the suppressed immunologic microenvironment in tumors. Taken together,
      STAT3 has emerged as a promising target in cancer immunotherapy.

PMID- 29222043
TI  - Catheter ablation of atrial fibrillation in patients with heart failure and
      preserved ejection fraction.
AB  - BACKGROUND: Few studies have examined outcomes of catheter ablation for atrial
      fibrillation (AF) in patients with heart failure (HF) with preserved ejection
      fraction (HFpEF). OBJECTIVE: The purpose of this study was to compare outcomes of
      AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF).
      METHODS: We performed a retrospective study of 230 patients with HF who underwent
      AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes
      included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York
      Heart Association (NYHA) functional class, and freedom from recurrent atrial
      arrhythmia at 12 months. RESULTS: Overall, 150 of 230 patients had nonparoxysmal
      AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left
      atrial diameter (4.4 +/- 0.8 cm vs 4.7 +/- 0.7 cm; P = .013) and were less likely
      to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1,
      Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P =
      .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar
      between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was
      not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted
      hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements
      in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (
      0.23 vs -0.09; P = .116) after ablation. CONCLUSION: Catheter ablation of AF
      seems to have similar effectiveness in patients with HF, regardless of presence
      of systolic dysfunction. There were no significant differences in procedural
      characteristics, arrhythmia-free recurrence, or functional improvements between
      patients with HFpEF and those with HFrEF.

PMID- 29222044
TI  - The effects of assurances of voluntary compliance on retail sales to minors in
      the United States: 2015-2016.
AB  - Multiple state attorneys generals have entered assurances of voluntary compliance
      (AVCs) with numerous national retail chains as an application of consumer
      protection laws to help prevent tobacco sales to minors. Little is known about
      the effectiveness of AVCs in reducing the violations of tobacco retailers for
      underage sales. We collected inspection data involving minors (n=53,832) on
      tobacco retailers in 2015 and 2016 from the Food and Drug Administration (FDA)
      compliance check database. Inspections on 13 national retail chains were
      classified into four categories: gas stations from oil companies, convenience
      stores, pharmacy stores, and supermarkets. Multilevel logistic regression models
      were performed to examine the effectiveness of AVCs, adjusted for state tobacco
      control policies, state youth smoking rates, and socio-economic status (SES) at
      census tracts. Overall the Retail Violation Rate for sales to minors (RVRm)
      significantly varied by retail category from 7.7% in pharmacy stores to 18.9% in
      gas stations from oil companies. Retailers that entered an AVC had lower odds of
      underage sales violations in convenience stores (aOR=0.75, 95% CI [0.61-0.93])
      and supermarkets (aOR=0.74, 95% CI [0.59-0.93]). For gas stations from oil
      companies and pharmacy stores, there were no significant differences in RVRm
      between stores with an AVC and stores without an AVC. We found that entering into
      AVCs is associated with fewer retail violations of underage sales for convenience
      stores and pharmacy stores. Continued efforts to strengthen the enforcement of
      AVCs and to expand AVCs to more states and other retail chains may improve youth
      tobacco control.

PMID- 29222046
TI  - Erratum to "Ultrasound-mediated nanoparticle delivery across ex vivo bovine
      retina after intravitreal injection" [Eur. J. Pharm. Biopharm. 119 (2017) 125
      136].

PMID- 29222045
TI  - Challenges in risk estimation using routinely collected clinical data: The
      example of estimating cervical cancer risks from electronic health-records.
AB  - Electronic health-records (EHR) are increasingly used by epidemiologists studying
      disease following surveillance testing to provide evidence for screening
      intervals and referral guidelines. Although cost-effective, undiagnosed prevalent
      disease and interval censoring (in which asymptomatic disease is only observed at
      the time of testing) raise substantial analytic issues when estimating risk that
      cannot be addressed using Kaplan-Meier methods. Based on our experience analysing
      EHR from cervical cancer screening, we previously proposed the logistic-Weibull
      model to address these issues. Here we demonstrate how the choice of statistical
      method can impact risk estimates. We use observed data on 41,067 women in the
      cervical cancer screening program at Kaiser Permanente Northern California, 2003
      2013, as well as simulations to evaluate the ability of different methods (Kaplan
      Meier, Turnbull, Weibull and logistic-Weibull) to accurately estimate risk within
      a screening program. Cumulative risk estimates from the statistical methods
      varied considerably, with the largest differences occurring for prevalent disease
      risk when baseline disease ascertainment was random but incomplete. Kaplan-Meier
      underestimated risk at earlier times and overestimated risk at later times in the
      presence of interval censoring or undiagnosed prevalent disease. Turnbull
      performed well, though was inefficient and not smooth. The logistic-Weibull model
      performed well, except when event times didn't follow a Weibull distribution. We
      have demonstrated that methods for right-censored data, such as Kaplan-Meier,
      result in biased estimates of disease risks when applied to interval-censored
      data, such as screening programs using EHR data. The logistic-Weibull model is
      attractive, but the model fit must be checked against Turnbull non-parametric
      risk estimates.

PMID- 29222047
TI  - Clown knifefish (Chitala ornata) oxygen uptake and its partitioning in present
      and future temperature environments.
AB  - It has been argued that tropical ectotherms are more vulnerable to the projected
      temperature increases than their temperate relatives, because they already live
      closer to their upper temperature limit. Here we examine the effects of a
      temperature increase in environmental temperature to 6 degrees C above the
      present day median temperature (27 degrees C) in the freshwater air-breathing
      fish Chitala ornata, on aspects of its respiratory physiology in both normoxia
      and in hypoxia. We found no evidence of respiratory impairment with elevated
      temperature. The standard metabolic rate (SMR) and routine metabolic rate (RMR)
      in the two temperatures in normoxia and hypoxia increased with Q10 values between
      2.3 and 2.9, while the specific dynamic action (SDA) and its coefficient
      increased from 7.8 to 14.7% in 27 degrees C and 33 degrees C, respectively. In
      addition, Chitala ornata exhibited significantly improved growth at the elevated
      temperature in both hypoxic and normoxic water. While projected temperature
      increases may negatively impact other essential aspects in this animal's
      environment, we see no evidence of a negative impact on this species itself.

PMID- 29222048
TI  - Coronary artery to pulmonary artery fistula visualized with 3D cinematic
      rendering.

PMID- 29222049
TI  - MTD-like motif of a BH3-only protein, BNIP1, induces necrosis accompanied by an
      intracellular calcium spike.
AB  - The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity
      when conjugated with cell-penetrating peptide (CPP). In this study, we report
      another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein
      found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with
      CPP, induced necrosis in a way similar to that of R8:MTD. R8:B1MLM caused an
      intracellular calcium spike, mitochondrial reactive oxygen species generation,
      and mitochondrial fragmentation. The cytosolic calcium spike was likely due to
      the opening of the mitochondrial permeability transition pore.

PMID- 29222050
TI  - Effects of the RNA-binding protein, KSRP, on innate immune response against
      Helicobacter pylori infection in mice.
AB  - Helicobacter pylori (H. pylori) contributes to various gastric diseases such as
      chronic gastritis, gastric ulcer, and gastric carcinoma. Host innate immune
      response against the pathogen plays a significant role in elimination of pathogen
      infection. Importantly, pathogen elimination is closely related to numerous
      inflammatory-related genes that participate in complex biological response of
      cells to harmful stimuli. Here we studied effects of the KH-type splicing
      regulatory protein (KSRP), a RNA-binding protein, on innate immune response
      against H. pylori infection. We found that H. pylori infection downregulated KSRP
      expression directly, and that KSRP overexpression repressed upregulation of CXCL
      2 expression induced by H. pylori and facilitated H. pylori proliferation in
      vitro. Similarly, KSRP overexpression in H. pylori mice also facilitated H.
      pylori proliferation and colonization, and induced more severe gastric mucosal
      damage. Intriguingly, CXCL-2 and HMOX-1 were upregulated in H. pylori infected
      mice after KSRP overexpression. This difference in expression of these genes
      implicated that KSRP was closely associated with and directly participated in the
      innate immune response against H. pylori. These results were beneficial for
      understanding the in vivo function of KSRP on innate immune response against
      pathogen infection.

PMID- 29222051
TI  - Long-term fermented soybean paste improves metabolic parameters associated with
      non-alcoholic fatty liver disease and insulin resistance in high-fat diet-induced
      obese mice.
AB  - Recently, Korean traditional fermented soybean paste, called Doenjang, has
      attracted attention for its protective effect against diet-related chronic
      diseases such as obesity and type 2 diabetes. Long-term fermented soybean pastes
      (LFSPs) are made by fermentation with naturally-occurring microorganisms for
      several months, whereas short-term fermented soybean pastes (SFSPs) are produced
      by shorter-time fermentation inoculated with a starter culture. Here, we
      demonstrate that administration of LFSP, but not SFSP, protects high-fat diet
      (HFD)-fed obese mice against non-alcohol fatty liver disease (NAFLD) and insulin
      resistance. LFSP suppressed body weight gain in parallel with reduction in fat
      accumulation in mesenteric adipose tissue (MAT) and the liver via modulation of
      MAT lipolysis and hepatic lipid uptake. LFSP-treated mice also had improved
      glucose tolerance and increased adiponectin levels concomitantly with enhanced
      AMPK activation in skeletal muscle and suppressed expression of pro-inflammatory
      cytokines in skeletal muscle and the liver. LFSP also attenuated HFD-induced gut
      permeability and lowered serum lipopolysaccharide level, providing an evidence
      for its probiotic effects, which was supported by the observation that treatment
      of a probiotic mixture of LFSP-originated Bacillus strains protected mice against
      HFD-induced adiposity and glucose intolerance. Our findings suggest that the
      intake of LFSP, but not SFSP, offers protection against NAFLD and insulin
      resistance, which is an effect of long-term fermentation resulting in elevated
      contents of active ingredients (especially flavonoids) and higher diversity and
      richness of Bacillus probiotic strains compared to SFSP.

PMID- 29222052
TI  - In vitro co-culture models to evaluate acute cytotoxicity of individual and
      combined mycotoxin exposures on Caco-2, THP-1 and HepaRG human cell lines.
AB  - Deoxynivalenol (DON) and zearalenone (ZEA) are mycotoxins primarily produced by
      Fusarium species and commonly co-occur in European grains. Some in vitro studies
      reported synergistic combined effects on cell viability reduction for these two
      natural food contaminants. However, most of these studies were carried out on
      conventional cell culture systems involving only one cell type and thus did not
      include cell-cell communication that is closer to in vivo conditions. In this
      context, we developed easy bi- and tri-culture systems using the Caco-2
      (intestinal epithelial cells), THP-1 (monocytes) and HepaRG (hepatic cells) human
      cell lines in a proliferating state. Individual and combined cytotoxic effects of
      DON and ZEA were then assessed using co-cultures during 48 h. In bi-culture
      systems, results showed that only the highest tested dose of ZEA (IC30) induced a
      significant reduction in THP-1 viability with both Caco-2 and HepaRG cells
      cultured in transwells above. On the contrary, only the highest tested dose of
      DON (IC30) significantly affected HepaRG cell viability located under the Caco-2
      cell monolayer. In addition, the DON + ZEA combination seemed to induce higher
      cytotoxicity than each toxin alone. Mycotoxin quantification in the abluminal
      compartment by Q-TOF LC-MS suggested uptake of both mycotoxins by the different
      cell lines. According to the co-culturing cell type, possible cell-cell
      interactions were also observed. Finally, in the tri-culture system, no cytotoxic
      effects were observed, regardless of the treatment. These findings highlighted
      the importance of the proposed models to better decipher toxicological impacts of
      mycotoxins on more complex cellular systems.

PMID- 29222054
TI  - Caramel color safety - An update.
AB  - Caramel color has been used in foods and beverages for over 150 years and is
      globally regulated as a color additive. The four distinct classes of caramel
      color (Plain Caramel, Sulfite Caramel, Ammonia Caramel, and Sulfite Ammonia
      Caramel) are well characterized and each have specifications that take into
      account processing variables including reactants that can give rise to low
      molecular weight constituents (e.g., 4-MeI and THI) that may have toxicological
      significance for evaluating safety. Extensive safety testing has been conducted
      with the different classes of caramel color and its constituents, including
      toxicokinetics, genotoxicity, subchronic toxicity, carcinogenicity, and
      reproductive/developmental toxicity studies. In addition, data is available on
      uses and use levels that have been used to estimate intakes of caramel colors and
      their constituents. No Observable Adverse Effect Levels (NOAEL) have been
      identified for all classes and Acceptable Daily Intakes have been established to
      ensure safety of use. Available studies support a conclusion that caramel colors
      are not genotoxic or carcinogenic, and exposure estimates indicate that intake of
      caramel colors and constituents do not pose undue safety risks. This update
      summarizes available relevant safety studies and authoritative reviews on caramel
      colors and its toxicologically important constituents, 4-MeI and THI.

PMID- 29222053
TI  - Assessment of the effect of cooking on speciation and bioaccessibility/cellular
      uptake of arsenic in rice, using in vitro digestion and Caco-2 and PSI cells as
      model.
AB  - In vitro digestion/Caco-2 or pig small intestinal epithelium cell line (PSI)
      uptake models were used to study the bioaccessibility and cellular uptake of
      arsenic (As) in cooked white rice and brown rice. The arsenite(AsIII), was the
      predominant species in cooked rice and in its bioaccessible fractions. The
      percentage of total As bioaccessibility in white rice (75%) was slightly higher
      (p=0.061) than that in brown rice(66%). However, there was no difference in the
      inorganic As (iAs) bioaccessibility between white rice (95%) and brown rice
      (96%). In Caco-2 cell monolayer, total As retention was 7-31%, transport was 4
      25%, and uptake (sum of retention and transport) was 16-38%. In PSI cell model,
      the retention, transport, and uptake of tAs were 10-28%, 14-31%, and 29-50%,
      respectively. In both cells, the cellular uptake of tAs in brown rice was 1.4-1.5
      folds lower (p<0.05) than that of white rice. These results indicate that the
      cellular uptake of As can be affected by nutritional compositions. These in vitro
      screening methods can serve as preliminary screens to predict the relative impact
      in rice matrix having different As species and processing conditions, although
      more research efforts should be applied to validating the existing in vitro
      methods.

PMID- 29222055
TI  - Autophagy plays a protective role in Mn-induced toxicity in PC12 cells.
AB  - Excessive environmental or occupational exposure to manganese (Mn) is associated
      with increased risk of neuron degenerative disorders. Oxidative stress and
      mitochondrial dysfunction are the main mechanisms of Mn mediated neurotoxicity.
      Selective removal of damaged mitochondria by autophagy has been proposed as a
      protective mechanism against neuronal toxicant-induced neurotoxicity. Whether
      autophagic flux plays a role in Mn-induced cytotoxicity remains to be fully
      elucidated. The present study was designed to investigate the effect of Mn
      exposure on autophagy, and how modulation of autophagic flux alters the
      sensitivities of cells to Mn-elicited cytotoxicity. Rat adrenal pheochromocytoma
      PC12 cells were treated with Mn for 24h to establish a cellular mode of Mn
      toxicity. Treatment of cells with Mn resulted in increased expression of
      autophagic marker LC3-II protein, as well as accumulation of p62, indicating an
      interference of autophagy flux caused by Mn. Pre-incubation of cells with
      antioxidant N-acetyl-l-cysteine (NAC) or resveratrol improved cell survival,
      accompanied by decreased LC3-II expression and increased expression level of p62,
      suggesting a down regulation of autophagy flux. To further determine the role of
      autophagy in Mn-induced cytotoxicity, the effect of chloroquine and rapamycin on
      cell viability was examined. Inhibition of autophagy flux by chloroquine
      exacerbated Mn-induced cytotoxicity, while induction of autophagy by rapamycin
      significantly reduced cell death caused by Mn. Furthermore, it was found that
      rapamycin, NAC and resveratrol improved cellular oxygen consumption accompanied
      by a decrease in cellular ROS generation and increase in GSH level, while
      chloroquine suppressed cellular respiration and deteriorated cellular oxidative
      stress. Collectively, these results demonstrate that autophagy plays a protective
      role in Mn-induced cell toxicity. Antioxidants NAC and resveratrol confer
      protective role in Mn toxicity mainly through maintaining mitochondrial dynamics
      and function, other than a modulation of autophagy flux.

PMID- 29222056
TI  - Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of
      randomized controlled trials.
AB  - OBJECTIVE: To clarify the effects of bisphosphonates in knee osteoarthritis (OA)
      using an up-to-date meta-analysis of randomized controlled trials (RCTs). DESIGN:
      The protocol is registered in PROSPERO (CRD42017073449). We searched MEDLINE,
      EMBASE, Google Scholar, Web of Science, and Cochrane Database from inception
      until August 2017. We included only RCTs comparing any bisphosphonates vs placebo
      in knee OA patients and reporting validated pain and function scales,
      radiographic progression, and adverse events (AEs) outcomes. We excluded studies
      using active comparators or concomitant medications besides non-steroidal anti
      inflammatory drugs (NSAIDs) and acetaminophen. We calculated standardized mean
      differences (SMDs) to account for variation in outcome scales. Random effects
      meta-analyses were performed. RESULTS: We included seven RCTs (3013 patients, 69%
      female); most patients (N = 2767) received oral risedronate. No pain or function
      outcomes, regardless of dose, route, time point or measuring instrument, revealed
      statistically significant results (end of trial pain SMD = -0.16 [95% confidence
      interval (CI): -0.34, 0.02]). Similarly, we found no statistically significant
      effect on radiographic progression (risk ratio = 0.98 [95% CI: 0.77, 1.26]). One
      small RCT in patients with bone marrow lesions (BMLs) suggested a reduction in
      BML size at 6 months. Bisphosphonates displayed good tolerability, with no
      statistically significant differences in AE outcomes vs placebo. CONCLUSIONS:
      Contrary to prior reviews, our analysis showed that bisphosphonates neither
      provide symptomatic relief nor defer radiographic progression in knee OA.
      However, these agents may still be beneficial in certain subsets of patients who
      display high rates of subchondral bone turnover. Future studies should be
      directed at defining such OA subsets and investigating the effects of
      bisphosphonates in those patients.

PMID- 29222057
TI  - Unfolding the cognitive map: The role of hippocampal and extra-hippocampal
      substrates based on a systems analysis of spatial processing.
AB  - What has been long absent in understanding the neural circuit that supports
      spatial processing is a thorough description and rigorous study of the
      distributed neural networks associated with spatial processing-both in the human
      as well as in rodents. Most of our understanding regarding the elucidation of a
      spatial neural circuit has been based on rodents and therefore the present
      manuscript will concentrate on that literature. There is a trend emerging in
      research to expand beyond the hippocampus for evaluating spatial memory, but the
      thrust of the research still focuses on the role of the hippocampus as essential
      and other neural substrates as performing sub-servient roles to support
      hippocampus-dependent spatial processing. This review will describe spatial
      memory in terms of a system model incorporating partially overlapping and
      interacting event-based, knowledge-based and rule-based memory systems that are
      composed of different component processes or attributes associated with spatial
      processing which are mapped onto the corresponding neural substrates and larger
      networks. In particular, the interactions among brain systems that process
      spatial information will be emphasized. We propose that these interactions among
      brain regions are essential for spatial memory.

PMID- 29222058
TI  - Differential expression of the immediate early genes c-Fos, Arc, Egr-1, and Npas4
      during long-term memory formation in the context preexposure facilitation effect
      (CPFE).
AB  - The context preexposure facilitation effect (CPFE) is a contextual fear
      conditioning paradigm in which learning about the context, acquiring the context
      shock association, and retrieving/expressing contextual fear are temporally
      dissociated into three distinct phases (context preexposure, immediate-shock
      training, and retention). The current study examined changes in the expression of
      plasticity-associated immediate early genes (IEGs) during context and contextual
      fear memory formation on the preexposure and training days of the CPFE,
      respectively. Using adolescent Long-Evans rats, preexposure and training day
      expression of the IEGs c-Fos, Arc, Egr-1, and Npas4 in the medial prefrontal
      cortex (mPFC), dorsal hippocampus (dHPC), and basolateral amygdala (BLA) was
      analyzed using qPCR as an extension of previous studies from our lab examining
      Egr-1 via in situ hybridization (Asok, Schreiber, Jablonski, Rosen, & Stanton,
      2013; Schreiber, Asok, Jablonski, Rosen, & Stanton, 2014). In Expt. 1, context
      preexposure induced expression of c-Fos, Arc, Egr-1 and Npas4 significantly above
      that of home-cage (HC) controls in all three regions. In Expt. 2, immediate-shock
      was followed by a post-shock freezing test, resulting in increased mPFC c-Fos
      expression in a group preexposed to the training context but not a control group
      preexposed to an alternate context, indicating expression related to associative
      learning. This was not seen with other IEGs in mPFC or with any IEG in dHPC or
      BLA. Finally, when the post-shock freezing test was omitted in Expt. 3, training
      related increases were observed in prefrontal c-Fos, Arc, Egr-1, and Npas4,
      hippocampal c-Fos, and amygdalar Egr-1 expression. These results indicate that
      context exposure in a post-shock freezing test re-engages IEG expression that may
      obscure associatively-induced expression during contextual fear conditioning.
      Additionally, these studies suggest a key role for long-term synaptic plasticity
      in the mPFC in supporting the CPFE.

PMID- 29222059
TI  - Some Cochrane risk-of-bias items are not important in osteoarthritis trials: a
      meta-epidemiological study based on Cochrane reviews.
AB  - OBJECTIVE: To evaluate the impact of bias-related study characteristics on
      treatment effects in osteoarthritis (OA) trials. STUDY DESIGN AND SETTING: Based
      on OA trials included in Cochrane reviews, the impact of study characteristics on
      treatment effect estimates was evaluated. Characteristics included items of the
      risk of bias (RoB) tool, trial size, single vs. multisite, and source of funding.
      Effect sizes (ESs) were calculated as standardized mean differences (SMDs). Meta
      regression was performed to identify "relevant study-level covariates" that
      decrease the between-study variance (tau^2). RESULTS: Twenty reviews, including
      126 OA trials with a high degree of heterogeneity, were included (tau^2 =
      0.1247). Among the RoB domains, only patient blinding had an impact on the
      results (reducing heterogeneity according to tau^2 < 7%). Inadequate blinding of
      patients yielded larger effects (SMDDifference = 0.15; 95% confidence interval
      [CI]: 0.01-0.29, P = 0.035). The most important study characteristic was trial
      size (heterogeneity reduced by 25%), with small trials reporting larger effects
      (SMDDifference = 0.29; 95% CI: 0.16-0.42, P < 0.001). CONCLUSION: In
      musculoskeletal reviews addressing pain, all the items included in the Cochrane
      RoB tool might not be equally important. OA trial results may be affected by bias
      constructs that are not yet fully elucidated.

PMID- 29222060
TI  - Cochrane Qualitative and Implementation Methods Group guidance series-paper 6:
      reporting guidelines for qualitative, implementation, and process evaluation
      evidence syntheses.
AB  - OBJECTIVES: To outline contemporary and novel developments for the presentation
      and reporting of syntheses of qualitative, implementation, and process evaluation
      evidence and provide recommendations for the use of reporting guidelines. STUDY
      DESIGN AND SETTING: An overview of reporting guidelines for qualitative,
      implementation, and process evaluation evidence syntheses drawing on current
      international literature and the collective expert knowledge of the Cochrane
      Qualitative and Implementation Methods Group. RESULTS: Several reporting
      guidelines exist that can be used or adapted to report syntheses of qualitative,
      implementation, and process evaluation evidence. Methods to develop individual
      guidance varied. The use of a relevant reporting guideline can enhance the
      transparency, consistency, and quality of reporting. Guidelines that exist are
      generic, method specific, and for particular aspects of the reviewing process,
      searching. CONCLUSION: Caution is expressed over the potential for reporting
      guidelines to produce a mechanistic approach moving the focus away from the
      content and toward the procedural aspects of the review. The use of a reporting
      guideline is recommended and a five-step decision flowchart to guide the choice
      of reporting guideline is provided. Gaps remain in method-specific reporting
      guidelines such as mixed-study, implementation, and process evaluation evidence
      syntheses.

PMID- 29222061
TI  - Differences between protocols for randomized controlled trials and systematic
      reviews.

PMID- 29222062
TI  - Evolutionary history of the cobalamin-independent methionine synthase gene family
      across the land plants.
AB  - Plants are successful paleopolyploids. The wide diversity of land plants is
      driven strongly by their gene duplicates undergoing distinct evolutionary fates
      after duplication. We used genomic resources from 35 model plant species to
      unravel the evolutionary fate of gene copies (paralogs) of the cobalamin
      independent methionine synthase (metE) gene family across the land plants. To
      explore genealogical relationships and characterize positive selection as a
      driving force in the evolution of metE paralogs within a single species, we
      carried out complementary analyses on genomic data of 32 genotypes of soybean.
      The size of the metE gene family remained small across the land plants; most of
      the studied species possessed 1-6 paralogs. Gene products were either cytosolic
      or chloroplastic; this dual subcellular distribution arose early during the
      divergence of the land plants and reached all extant lineages. Biased gene loss
      and gene retention events took place multiple times; recurrent evolution
      remodeled redundant metE paralogs to recover and maintain the dual subcellular
      distribution of MetE. Shared whole-genome duplication events gave rise to the
      metE paralogs of both soybean and Medicago truncatula. In soybean, the ancestral
      paralog pair GlymaPP2A encoded a cytosolic isoform of MetE, was under strong
      purifying selection, and retained high levels of expression across eight RNA-seq
      expression libraries. The daughters GlymaPP1 and GlymaPP2B showed accelerated
      rates of evolution, accumulated many sites predicted to be under positive
      selection, and possessed low levels of expression. Our results suggest that the
      metE paralogs of soybean follow Ohno's neofunctionalization model of gene
      duplicate evolution.

PMID- 29222063
TI  - Evolutionary dynamism in bryophytes: Phylogenomic inferences confirm rapid
      radiation in the moss family Funariaceae.
AB  - Rapid diversifications of plants are primarily documented and studied in
      angiosperms, which are perceived as evolutionarily dynamic. Recent studies have,
      however, revealed that bryophytes have also undergone periods of rapid radiation.
      The speciose family Funariaceae, including the model taxon Physcomitrella patens,
      is one such lineage. Here, we infer relationships among major lineages within the
      Entosthodon-Physcomitrium complex from virtually complete organellar exomes
      (i.e., 123 genes) obtained through high throughput sequencing of genomic
      libraries enriched in these loci via targeted locus capture. Based on these
      extensive exonic data we (1) reconstructed a robust backbone topology of the
      Funariaceae, (2) confirmed the monophyly of Funaria and the polyphyly of
      Entosthodon, Physcomitrella, and Physcomitrium, and (3) argue for the occurrence
      of a rapid radiation within the Entosthodon-Physcomitrium complex that began 28
      mya and gave rise more than half of the species diversity of the family. This
      diversification may have been triggered by a whole genome duplication and
      coincides with global Eocene cooling that continued through the Oligocene and
      Miocene. The Funariaceae join a growing list of bryophyte lineages whose history
      is marked by at least one burst of diversification, and our study thereby
      strengthens the view that bryophytes are evolutionarily dynamic lineages and that
      patterns and processes characterizing the evolution of angiosperms may be
      universal among land plants.

PMID- 29222065
TI  - Testing the monophyly of Simaba (Simaroubaceae): Evidence from five molecular
      regions and morphology.
AB  - Generic circumscriptions in the mostly pantropical family Simaroubaceae are
      somewhat controversial. Simaba is the largest genus, currently defined as
      exclusively neotropical, with around 25 species of trees and shrubs, but both its
      limits and infrageneric classification have been a matter of discussion and
      divergence. Traditionally, species of the genus have been treated in three
      sections: Simaba sect. Tenuiflorae, S. sect. Floribundae and S. sect.
      Grandiflorae, but a phylogenetic analysis suggested that the latter two may not
      be monophyletic. To test the monophyly of Simaba and its infrageneric
      classification, we used a molecular approach based on DNA sequence data from two
      nuclear ribosomal spacer regions (ITS and ETS) and three plastid regions (rps16
      intron, and intergenic spacers psbA-trnH and trnL-trnF), including a
      comprehensive sampling of species from Simaba and closely related genera. We also
      performed ancestral character reconstructions to identify morphological
      characters that could serve as synapomorphies for major clades and to explore
      patterns of homoplasy in the morphological dataset. Our results show Simaba as
      traditionally circumscribed is not monophyletic, with taxa segregated into two
      strongly supported but distinct clades, one of which is more closely related to
      Simarouba. The three main clades that emerged in the phylogeny include a mostly
      Amazonian Simaba clade (which includes the type species of Simaba and the
      remaining species of S. sect. Tenuiflorae, here proposed to be recognized as
      Simaba sensu stricto), a mostly extra-Amazonian Simaba clade (a distinct lineage
      that will be recognized as Homalolepis, a genus currently treated in synonymy and
      equivalent to Simaba sections Grandiflorae and Floribundae), and the Simarouba
      clade (including all of its current species). These three clades are
      characterized by a combination of morphological characters, described in detail
      herein, some of which are novel features for Simaba not previously reported in
      the literature. Mapping character-states on the phylogenetic tree provides tests
      for evolutionary hypotheses. For example, our reconstruction of habit and
      geographic distribution suggests that the diversification of several shrubby
      species within the extra-Amazonian lineage in the South American cerrados
      probably occurred from ancestors inhabiting tropical forests, involving
      transitions in morphological and ecological traits.

PMID- 29222064
TI  - Evolution in the Amphi-Atlantic tropical genus Guibourtia (Fabaceae,
      Detarioideae), combining NGS phylogeny and morphology.
AB  - Tropical rain forests support a remarkable diversity of tree species, questioning
      how and when this diversity arose. The genus Guibourtia (Fabaceae, Detarioideae),
      characterized by two South American and 13 African tree species growing in
      various tropical biomes, is an interesting model to address the role of
      biogeographic processes and adaptation to contrasted environments on species
      diversification. Combining whole plastid genome sequencing and morphological
      characters analysis, we studied the timing of speciation and diversification
      processes in Guibourtia through molecular dating and ancestral habitats
      reconstruction. All species except G. demeusei and G. copallifera appear
      monophyletic. Dispersal from Africa to America across the Atlantic Ocean is the
      most plausible hypothesis to explain the occurrence of Neotropical Guibourtia
      species, which diverged ca. 11.8 Ma from their closest African relatives. The
      diversification of the three main clades of African Guibourtia is concomitant to
      Miocene global climate changes, highlighting pre-Quaternary speciation events.
      These clades differ by their reproductive characters, which validates the three
      subgenera previously described: Pseudocopaiva, Guibourtia and Gorskia. Within
      most monophyletic species, plastid lineages start diverging from each other
      during the Pliocene or early Pleistocene, suggesting that these species already
      arose during this period. The multiple transitions between rain forests and dry
      forests/savannahs inferred here through the plastid phylogeny in each Guibourtia
      subgenus address thus new questions about the role of phylogenetic relationships
      in shaping ecological niche and morphological similarity among taxa.

PMID- 29222066
TI  - Large-scale randomized clinical trials of bioactives and nutrients in relation to
      human health and disease prevention - Lessons from the VITAL and COSMOS trials.
AB  - Several bioactive compounds and nutrients in foods have physiological properties
      that are beneficial for human health. While nutrients typically have clear
      definitions with established levels of recommended intakes, bioactive compounds
      often lack such a definition. Although a food-based approach is often the optimal
      approach to ensure adequate intake of bioactives and nutrients, these components
      are also often produced as dietary supplements. However, many of these
      supplements are not sufficiently studied and have an unclear role in chronic
      disease prevention. Randomized trials are considered the gold standard of study
      designs, but have not been fully applied to understand the effects of bioactives
      and nutrients. We review the specific role of large-scale trials to test whether
      bioactives and nutrients have an effect on health outcomes through several
      crucial components of trial design, including selection of intervention,
      recruitment, compliance, outcome selection, and interpretation and
      generalizability of study findings. We will discuss these components in the
      context of two randomized clinical trials, the VITamin D and OmegA-3 TriaL
      (VITAL) and the COcoa Supplement and Multivitamin Outcomes Study (COSMOS). We
      will mainly focus on dietary supplements of bioactives and nutrients while also
      emphasizing the need for translation and integration with food-based trials that
      are of vital importance within nutritional research.

PMID- 29222067
TI  - Role of extracellular vesicles in glioma progression.
AB  - The role of extracellular vesicles in cancer biology has emerged as a focus of
      the study of great importance and has been shown to directly influence tumour
      development in several cancers including brain tumours, such as gliomas. Gliomas
      are the most aggressive brain tumours, and in the last time, a considerable
      effort has been made to understand their biology. Studies focus in the signalling
      pathways involved in the processes of angiogenesis, viability, drug resistance
      and immune response evasion, as well as gliomas ability to infiltrate healthy
      tissue, a phenomenon regulated by the migratory and invasive capacity of the
      cells within a tumour. In this review, we summarize the different types and
      classifications of extracellular vesicles, their intravesicular content, and
      their role in the regulation of tumour progression processes in glioma.

PMID- 29222068
TI  - Foetoplacental communication via extracellular vesicles in normal pregnancy and
      preeclampsia.
AB  - Intercellular communication is a critical process in biological mechanisms.
      During pregnancy foetoplacental tissues release a heterogeneous group of
      extracellular vesicles (EVs) that include exosomes, microvesicles, apoptotic
      bodies, and syncytial nuclear aggregates. These vesicles contain a complex cargo
      (proteins, DNA, mRNA transcripts, microRNAs, noncoding RNA, lipids, and other
      molecules) that actively participate in the maternal-foetal communication by
      modulating different processes during gestation for a successful foetal
      development. Each stage of human gestation is marked by events such as
      immunomodulation, proliferation, invasion, migration, and differentiation, among
      others, requiring EVs-mediated signalling to be nearby or distant target cells.
      Furthermore, EVs also associate with pregnancy pathologies such as preeclampsia
      and intrauterine growth restriction. This review addresses the role of EVs in
      human foetomaternal communication in normal pregnancy and preeclampsia.

PMID- 29222069
TI  - Cooperativity between different tRNA modifications and their modification
      pathways.
AB  - Ribonucleotide modifications perform a wide variety of roles in synthesis,
      turnover and functionality of tRNA molecules. The presence of particular chemical
      moieties can refine the internal interaction network within a tRNA molecule,
      influence its thermodynamic stability, contribute novel chemical properties and
      affect its decoding behavior during mRNA translation. As the lack of specific
      modifications in the anticodon stem and loop causes disrupted proteome
      homeostasis, diminished response to stress conditions, and the onset of human
      diseases, the underlying modification cascades have recently gained particular
      scientific and clinical interest. Nowadays, a complicated but conclusive image of
      the interconnectivity between different enzymatic modification cascades and their
      resulting tRNA modifications emerges. Here we summarize the current knowledge in
      the field, focusing on the known instances of cross talk among the enzymatic tRNA
      modification pathways and the consequences on the dynamic regulation of the tRNA
      modificome by various factors. This article is part of a Special Issue entitled:
      SI: Regulation of tRNA synthesis and modification in physiological conditions and
      disease edited by Dr. Boguta Magdalena.

PMID- 29222070
TI  - Regulation of tRNA biogenesis in plants and its link to plant growth and response
      to pathogens.
AB  - The field of tRNA biology, encompassing the functional and structural complexity
      of tRNAs, has fascinated scientists over the years and is continuously growing.
      Besides their fundamental role in protein translation, new evidence indicates
      that tRNA-derived molecules also regulate gene expression and protein synthesis
      in all domains of life. This review highlights some of the recent findings
      linking tRNA transcription and modification with plant cell growth and response
      to pathogens. In fact, mutations in proteins directly involved in tRNA synthesis
      and modification most often lead to pleiotropic effects on plant growth and
      immunity. As plants need to optimize and balance their energy and nutrient
      resources towards growth and defense, regulatory pathways that play a central
      role in integrating tRNA transcription and protein translation with cell growth
      control and organ development, such as the auxin-TOR signaling pathway, also
      influence the plant immune response against pathogens. As a consequence, distinct
      pathogens employ an array of effector molecules including tRNA fragments to
      target such regulatory pathways to exploit the plant's translational capacity,
      gain access to nutrients and evade defenses. An example includes the RNA
      polymerase III repressor MAF1, a conserved component of the TOR signaling pathway
      that controls ribosome biogenesis and tRNA synthesis required for plant growth
      and which is targeted by a pathogen effector molecule to promote disease. This
      article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and
      modification in physiological conditions and disease edited by Dr. Boguta
      Magdalena.

PMID- 29222071
TI  - HDAC11 is a regulator of diverse immune functions.
AB  - Histone deacetylases deacetylate histone and non-histone protein targets.
      Aberrant HDAC expression and function have been observed in several diseases,
      which make these enzymes attractive treatment targets. Here, we summarize recent
      literature that addresses the roles of HDAC11 on the regulation of different
      immune cells including neutrophils, myeloid derived suppressor cells and T-cells.
      HDAC11 was initially identified as a negative regulator of the well-known anti
      inflammatory cytokine IL-10. Hence, antagonizing HDAC11 activity may have anti
      tumor potential, whereas activating HDAC11 may be useful to treat chronic
      inflammation or autoimmunity. However, to anticipate biological side-effects of
      HDAC11 modulators, more molecular insights will be required.

PMID- 29222073
TI  - Functional Impairments in a Patient with Morvan Syndrome: A Case Presentation.
AB  - : A 48-year-old man with lung squamous cell carcinoma was admitted to acute care
      with cognitive impairment after recent chemotherapy. He developed myoclonus,
      ataxia, agitation, and visual hallucinations. Morvan syndrome, a rare voltage
      gated potassium channel antibody disorder characterized by neuromyotonia with
      central nervous system dysfunction, was eventually diagnosed. He received
      plasmapheresis and was admitted to inpatient rehabilitation, where he safely
      participated in therapies. By focusing on neuromuscular rehabilitation, balance
      training, fine motor skills, and cognitive retraining emphasizing skills relevant
      to the patient's premorbid cognitive activities, the patient demonstrated
      significant functional improvement, decreasing the burden of care of his
      caregivers. LEVEL OF EVIDENCE: V.

PMID- 29222072
TI  - Heparan sulfate potentiates leukocyte adhesion on cardiac fibroblast by enhancing
      Vcam-1 and Icam-1 expression.
AB  - : Cardiac fibroblasts (CF) act as sentinel cells responding to chemokines,
      cytokines and growth factors released in cardiac tissue in cardiac injury events,
      such as myocardial infarction (MI). Cardiac injury involves the release of
      various damage-associated molecular patterns (DAMPs) including heparan sulfate
      (HS), a constituent of the extracellular matrix (ECM), through the TLR4 receptor
      activation triggering a strong inflammatory response, inducing leukocytes
      recruitment. This latter cells are responsible of clearing cell debris and
      releasing cytokines that promote CF differentiation to myofibroblast (CMF), thus
      initiating scar formation. CF were isolated from adult male rats and subsequently
      stimulated with HS or LPS, in the presence or absence of chemical inhibitors, to
      evaluate signaling pathways involved in ICAM-1 and VCAM-1 expression. siRNA
      against ICAM-1 and VCAM-1 were used to evaluate participation of these adhesion
      molecules on leukocytes recruitment. HS through TLR4, PI3K/AKT and NF-KappaB
      increased ICAM-1 and VCAM-1 expression, which favored the adhesion of spleen
      mononuclear cells (SMC) and bone marrow granulocytes (PMN) to CF. These effects
      were prevented by siRNA against ICAM-1 and VCAM-1. Co-culture of CF with SMC
      increased alpha-SMA expression, skewing CF towards a pro-fibrotic phenotype,
      while CF pretreatment with HS partially reverted this effect. CONCLUSION: These
      data show the dual role of HS during the initial stages of wound healing.
      Initially, HS enhance the pro-inflammatory role of CF increasing cytokines
      secretion; and later, by increasing protein adhesion molecules allows the
      adhesion of SMC on CF, which trigger CF-to-CMF differentiation.

PMID- 29222074
TI  - Changes in Oxygen Consumption and Heart Rate After Acute Myocardial Infarction
      During 6-Month Follow-up.
AB  - BACKGROUND: Exercise intensity is a particularly important determinant of
      physiological responses to exercise training in patients with acute myocardial
      infarction. Heart rate (HR) is commonly used as a practical way of prescribing
      and monitoring exercise as specific intensities based on a linear relationship
      between the percentage of maximum HR (%HRmax) and the percentage of maximum
      oxygen consumption (%VO2max) regardless of age, gender, or exercise mode.
      OBJECTIVE: To examine the change in variability in the correlation between %HRmax
      and %VO2max after acute myocardial infarction. DESIGN: Retrospective study.
      SETTING: Regional cardio-cerebrovascular center at a tertiary hospital. PATIENTS:
      A total of 66 patients were enrolled who were referred for cardiac rehabilitation
      (CR) after percutaneous intervention, and who had reached stage 3 of the modified
      Bruce Protocol (mBP) on an exercise tolerance test (ETT). METHODS: There were 54
      men and 12 women with an average age of 56.7 +/- 9.48 years, ejection fraction
      (EF) of 56.4% +/- 8.89%, and body mass index (BMI) of 24.73 +/- 2.86 kg/m2. All
      patients participated in a 4-week outpatient CR program and underwent ETT with a
      gas analyzer to determine maximal heart rate and maximal oxygen consumption
      before CR and 1 month, 3 months, and 6 months after CR. MAIN OUTCOME
      MEASUREMENTS: VO2max and HRmax were defined as the highest values attained during
      the ETT. The HR and VO2 values at each stage of the mBP were expressed as
      percentages of their maximum. %HRmax and %VO2max were calculated at each stage of
      the mBP. RESULTS: The maximum METs and VO2max significantly improved at 1 month
      after CR, but not significantly at 3 and 6 months after CR. The correlation
      between VO2max and HRmax progressively changed in a favorable manner during CR.
      The relationship between %HRmax and %VO2max indicated a coefficient of variation
      before and 1, 3, and 6 months after of 0.800, 0.826, 0.832, and 0.880,
      respectively. CONCLUSIONS: This study showed that the %HRmax correlates better
      with the %VO2max in the late-stage post-AMI than in the initial stage. We should
      therefore set and monitor the exercise intensity using maximal oxygen consumption
      in the early stage of exercise training after onset of acute myocardial
      infarction. LEVEL OF EVIDENCE: IV.

PMID- 29222075
TI  - Examining Tensions That Affect the Evaluation of Technology in Health Care:
      Considerations for System Decision Makers From the Perspective of Industry and
      Evaluators.
AB  - Virtual technologies have the potential to mitigate a range of challenges for
      health care systems. Despite the widespread use of mobile devices in everyday
      life, they currently have a limited role in health service delivery and clinical
      care. Efforts to integrate the fast-paced consumer technology market with health
      care delivery exposes tensions among patients, providers, vendors, evaluators,
      and system decision makers. This paper explores the key tensions between the high
      bar for evidence prior to market approval that guides health care regulatory
      decisions and the "fail fast" reality of the technology industry. We examine
      three core tensions: balancing user needs versus system needs, rigor versus
      responsiveness, and the role of pre- versus postmarket evidence generation. We
      use these to elaborate on the structure and appropriateness of evaluation
      mechanisms for virtual care solutions. Virtual technologies provide a foundation
      for personalized, patient-centered medicine on the user side, coupled with a
      broader understanding of impact on the system side. However, mechanisms for
      stakeholder discussion are needed to clarify the nature of the health technology
      marketplace and the drivers of evaluation priorities.

PMID- 29222077
TI  - Can Facebook Reduce Perceived Anxiety Among College Students? Randomized
      Controlled Exercise Trial Using the Transtheoretical Model of Behavior Change.
AB  - BACKGROUND: Recent studies suggest social media may be an attractive strategy to
      promote mental health and wellness. There remains a need to examine the utility
      for individually tailored wellness messages posted to social media sites such as
      Facebook to facilitate positive psychological outcomes. OBJECTIVE: Our aim was to
      extend the growing body of evidence supporting the potential for social media to
      enhance mental health. We evaluated the influence of an 8-week social media
      intervention on anxiety in college students and examined the impact of dynamic
      (active) versus static (passive) Facebook content on physical activity behaviors.
      METHODS: Participants in the static group (n=21) accessed a Facebook page
      featuring 96 statuses. Statuses were intended to engage cognitive processes
      followed by behavioral processes of change per the transtheoretical model of
      behavior change. Content posted on the static Facebook page was identical to the
      dynamic page; however, the static group viewed all 96 statuses on the first day
      of the study, while the dynamic group received only 1 to 2 of these status
      updates per day throughout the intervention. Anxiety was measured using the
      Overall Anxiety Severity and Impairment Scale (OASIS). Time spent engaging in
      physical activity was assessed using the International Physical Activity
      Questionnaire (IPAQ). RESULTS: The OASIS change score for the dynamic Facebook
      group was statistically significant (P=.003), whereas the change score for the
      static group was not (P=.48). A statistically significant group-by-time
      interaction was observed (P=.03). The total IPAQ group-by-time interaction was
      not statistically significant (P=.06). CONCLUSIONS: We observed a decrease in
      anxiety and increase in total physical activity for the dynamic group only.
      Dynamic social networking sites, featuring regularly updated content, may be more
      advantageous than websites that retain static content over time. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT03363737;
      https://clinicaltrials.gov/ct2/show/NCT03363737 (Archived by WebCite at
      http://www.webcitation.org/6vXzNbOWJ).

PMID- 29222076
TI  - Adverse Drug Event Discovery Using Biomedical Literature: A Big Data Neural
      Network Adventure.
AB  - BACKGROUND: The study of adverse drug events (ADEs) is a tenured topic in medical
      literature. In recent years, increasing numbers of scientific articles and health
      related social media posts have been generated and shared daily, albeit with very
      limited use for ADE study and with little known about the content with respect to
      ADEs. OBJECTIVE: The aim of this study was to develop a big data analytics
      strategy that mines the content of scientific articles and health-related Web
      based social media to detect and identify ADEs. METHODS: We analyzed the
      following two data sources: (1) biomedical articles and (2) health-related social
      media blog posts. We developed an intelligent and scalable text mining solution
      on big data infrastructures composed of Apache Spark, natural language
      processing, and machine learning. This was combined with an Elasticsearch No-SQL
      distributed database to explore and visualize ADEs. RESULTS: The accuracy,
      precision, recall, and area under receiver operating characteristic of the system
      were 92.7%, 93.6%, 93.0%, and 0.905, respectively, and showed better results in
      comparison with traditional approaches in the literature. This work not only
      detected and classified ADE sentences from big data biomedical literature but
      also scientifically visualized ADE interactions. CONCLUSIONS: To the best of our
      knowledge, this work is the first to investigate a big data machine learning
      strategy for ADE discovery on massive datasets downloaded from PubMed Central and
      social media. This contribution illustrates possible capacities in big data
      biomedical text analysis using advanced computational methods with real-time
      update from new data published on a daily basis.

PMID- 29222078
TI  - Texting Condolences: Adapting mHealth Programs After Unexpected Pregnancy and
      Infant Outcomes.
AB  - Mobile health (mHealth) short message system (SMS) interventions for maternal and
      child health (MCH) are being implemented globally. In many low- and middle-income
      settings in which these mHealth interventions are being rolled out, stillbirths
      and neonatal and infant deaths are common. It is important that mHealth solutions
      do not exacerbate emotional stress and pain by continuing with routine messaging
      for pregnancy or infant care when someone has experienced loss. In this brief
      viewpoint paper, we argue that SMS programs for maternal and child health need to
      adapt and make available messaging for miscarriage, stillbirth, and infant loss.

PMID- 29222079
TI  - Web-Based Interventions Supporting Adolescents and Young People With Depressive
      Symptoms: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Although previous studies on information and communication technology
      (ICT)-based intervention on mental health among adolescents with depressive
      symptoms have already been combined in a number of systematic reviews, coherent
      information is still missing about interventions used, participants' engagement
      of these interventions, and how these interventions work. OBJECTIVE: We conducted
      a systematic review and meta-analysis of trials to describe the effectiveness of
      Web-based interventions to support adolescents with depression or depressive
      symptoms, anxiety, and stress. We also explored the content of the interventions,
      as there has previously been a lack of coherent understanding of the detailed
      content of the Web-based interventions for these purposes. METHODS: We included
      parallel randomized controlled trials targeted at adolescents, or young people in
      the age range of 10 and 24 years, with symptoms or diagnoses of depression and
      anxiety. The interventions were from original studies aimed to support mental
      health among adolescents, and they were delivered via Web-based information and
      communication technology. RESULTS: Out of 2087 records identified, 27 papers (22
      studies) met the inclusion criteria. On the basis of a narrative analysis of 22
      studies, a variety of Web-based interventions were found; the most commonly used
      intervention was based on cognitive behavioral therapy. Meta-analysis was further
      conducted with 15 studies (4979 participants). At the end of the intervention, a
      statistically significant improvement was found in the intervention group (10
      studies) regarding depressive symptoms (P=.02, median 1.68, 95% CI 3.11-0.25) and
      after 6 months (3 studies; P=.01, median 1.78, 95% CI 3.20-0.37). Anxiety
      symptoms (8 studies; P<.001, median 1.47, 95% CI 2.36-0.59) and moods and
      feelings (2 studies; P=.04, median 5.55, 95% CI 10.88-0.22) improved as well in
      the Web-based intervention group, but there was no difference in stress scores.
      However, adolescents in the intervention group left the study early more often,
      both in short-term studies (11 studies; P=.007, median 1.31, 95% CI 1.08-1.58)
      and mid-term studies (3 studies; P=.02, median 1.65, 95% CI 1.09-2.49). We did
      not find any studies that had assessed the costs of the Web-based interventions.
      CONCLUSIONS: Despite widely reported promises that information technology use is
      beneficial to adolescents with depression, the results of our review show only
      short-term effects on adolescents' mental well-being, whereas long-term effects
      remain questionable because of the limited number of studies reviewed.
      Information about the economic benefits of Web-based interventions is still
      lacking. The quality of the studies, especially biases related to attrition rates
      and selective reporting, still needs serious attention.

PMID- 29222080
TI  - The 12-item Self-Report World Health Organization Disability Assessment Schedule
      (WHODAS) 2.0 Administered Via the Internet to Individuals With Anxiety and Stress
      Disorders: A Psychometric Investigation Based on Data From Two Clinical Trials.
AB  - BACKGROUND: The World Health Organization Disability Assessment Schedule 2.0
      (WHODAS 2.0) is a widespread measure of disability and functional impairment,
      which is bundled with the Diagnostic and Statistical Manual of Mental Disorders
      (Fifth Edition) for use in psychiatry. Administering psychometric scales via the
      Internet is an effective way to reach respondents and allow for convenient
      handling of data. OBJECTIVE: The aim was to study the psychometric properties of
      the 12-item self-report WHODAS 2.0 when administered online to individuals with
      anxiety and stress disorders. The WHODAS 2.0 was hypothesized to exhibit high
      internal consistency and be unidimensional. We also expected the WHODAS 2.0 to
      show high 2-week test-retest reliability, convergent validity (correlations
      approximately .50 to .90 with other self-report measures of functional
      impairment), that it would differentiate between patients with and without
      exhaustion disorder, and that it would respond to change in primary symptom
      domain. METHODS: We administered the 12-item self-report WHODAS 2.0 online to
      patients with anxiety and stress disorders (N=160) enrolled in clinical trials of
      cognitive behavior therapy, and analyzed psychometric properties within a
      classical test theory framework. Scores were compared with well-established
      symptom and disability measures, and sensitivity to change was studied from
      pretreatment to posttreatment assessment. RESULTS: The 12-item self-report WHODAS
      2.0 showed high internal consistency (Cronbach alpha=.83-.92), high 2-week test
      retest reliability (intraclass correlation coefficient=.83), adequate construct
      validity, and was sensitive to change. We found preliminary evidence for a three
      factorial structure, but one strong factor accounted for a clear majority of the
      variance. CONCLUSIONS: We conclude that the 12-item self-report WHODAS 2.0 is a
      psychometrically sound instrument when administered online to individuals with
      anxiety and stress disorders, but that it is probably fruitful to also report the
      three subfactors to facilitate comparisons between studies. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02540317; https://clinicaltrials.gov/ct2/show/NCT02540317
      (Archived by WebCite at http://www.webcitation.org/6vQEdYAem); Clinicaltrials.gov
      NCT02314065; https://clinicaltrials.gov/ct2/show/NCT02314065 (Archived by WebCite
      at http://www.webcitation.org/6vQEjlUU8).

PMID- 29222081
TI  - Media Consumption and Creation in Attitudes Toward and Knowledge of Inflammatory
      Bowel Disease: Web-Based Survey.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal
      condition affecting over 5 million people globally and 1.6 million in the United
      States but currently lacks a precisely determined cause or cure. The range of
      symptoms IBD patients experience are often debilitating, and the societal stigmas
      associated with some such symptoms can further degrade their quality of life.
      Better understanding the nature of this public reproach then is a critical
      component for improving awareness campaigns and, ultimately, the experiences of
      IBD patients. OBJECTIVE: The objective of this study was to explore and assess
      the public's awareness and knowledge of IBD, as well as what relationship, if
      any, exists between the social stigma surrounding IBD, knowledge of the disease,
      and various media usage, including social media. METHODS: Utilizing a Web-based
      opt-in platform, we surveyed a nationally representative sample (n=1200) with
      demographics mirroring those of the US Census figures across baseline parameters.
      Using constructed indices based on factor analysis, we were able to build
      reliable measures of personal characteristics, media behaviors, and perceptions
      and knowledge of IBD. RESULTS: Among the American public, IBD is the most
      stigmatized of seven diseases, including genital herpes and human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
      Additionally, IBD knowledge is generally low with 11.08% (133/1200) of the sample
      indicating no familiarity with the disease and 85.50% (1026/1200) of participants
      inaccurately answering two-thirds of the IBD index questions with which their
      knowledge was assessed. Increased knowledge of IBD is associated with lower
      levels of stigma. However, social media use is currently related to lower levels
      of IBD knowledge (P<.05). Furthermore, findings indicate that participants who
      most frequently engaged in producing social media content are less knowledgeable
      about IBD (P<.10), highlighting the potential for a dangerous cycle should they
      be contributing to a Web-based IBD dialogue. CONCLUSIONS: Greater efforts must be
      taken to stymie IBD misinformation across all media, but especially in social
      media channels, to increase IBD knowledge and reduce stigma surrounding IBD.
      These findings pave the way for further research qualitatively examining the
      pervasiveness of specific IBD messages found in today's social media landscape
      and their impact on enacted stigmas so as to better equip providers and patient
      advocacy organizations with impactful communication solutions.

PMID- 29222082
TI  - Bawa-Garba case: "When something goes wrong in healthcare there is never one
      person to blame".

PMID- 29222083
TI  - An Anglo-American medical lexicon.

PMID- 29222084
TI  - Judge grants anonymity to hospital treating brain damaged baby to protect staff.

PMID- 29222085
TI  - Different shell, same shock.

PMID- 29222088
TI  - Can we make informed consent forms more informative?

PMID- 29222086
TI  - Genome-wide DNA methylation profiling using the methylation-dependent restriction
      enzyme LpnPI.
AB  - DNA methylation is a well-known epigenetic modification that plays a crucial role
      in gene regulation, but genome-wide analysis of DNA methylation remains
      technically challenging and costly. DNA methylation-dependent restriction enzymes
      can be used to restrict CpG methylation analysis to methylated regions of the
      genome only, which significantly reduces the required sequencing depth and
      simplifies subsequent bioinformatics analysis. Unfortunately, this approach has
      been hampered by complete digestion of DNA in CpG methylation-dense regions,
      resulting in fragments that are too small for accurate mapping. Here, we show
      that the activity of DNA methylation-dependent enzyme, LpnPI, is blocked by a
      fragment size smaller than 32 bp. This unique property prevents complete
      digestion of methylation-dense DNA and allows accurate genome-wide analysis of
      CpG methylation at single-nucleotide resolution. Methylated DNA sequencing (MeD
      seq) of LpnPI digested fragments revealed highly reproducible genome-wide CpG
      methylation profiles for >50% of all potentially methylated CpGs, at a sequencing
      depth less than one-tenth required for whole-genome bisulfite sequencing (WGBS).
      MeD-seq identified a high number of patient and tissue-specific differential
      methylated regions (DMRs) and revealed that patient-specific DMRs observed in
      both blood and buccal samples predict DNA methylation in other tissues and
      organs. We also observed highly variable DNA methylation at gene promoters on the
      inactive X Chromosome, indicating tissue-specific and interpatient-specific
      escape of X Chromosome inactivation. These findings highlight the potential of
      MeD-seq for high-throughput epigenetic profiling.

PMID- 29222087
TI  - Dose-dependent relationship between acidosis at birth and likelihood of death or
      cerebral palsy.
AB  - BACKGROUND: The acid-base status of infants around birth can provide information
      about their past, current and future condition. Although umbilical cord blood pH
      <7.0 or base deficit >=12 mmol/L is associated with increased risk of adverse
      outcome, there is uncertainty about the prognostic value of degree of acidosis as
      previous studies have used different variables, thresholds, outcomes and
      populations. METHODS: Retrospective review of routinely collected clinical data
      in all live-born inborn infants of 35 weeks gestation or more delivered between
      January 2005 and December 2013 at the Simpson Centre for Reproductive Health,
      Edinburgh, UK. Infants were included if their lowest recorded pH was <7 and/or
      highest base deficit >=12 mmol/L on either umbilical cord blood and/or neonatal
      blood gas within 1 hour of birth. Neurodevelopmental outcome of the infants with
      encephalopathy was collected from the targeted follow-up database. RESULTS: 56
      574 infants were eligible. 506 infants (0.9%) met inclusion criteria. Poor
      condition at birth and all adverse outcomes increased with worsening acidosis.
      Combined outcome of death or cerebral palsy was 3%, 10% and 40% at lowest pH of
      6.9-6.99, 6.8-6.89 and <6.8, respectively, and 8%, 14% and 59% at a base deficit
      of 12-15.9, 16-19.9 and 20 mmol/L or more, respectively. CONCLUSIONS: There is a
      dose-dependent relationship between the degree of acidosis within an hour of
      delivery, and the likelihood of adverse neonatal and later neurodevelopmental
      outcome in infants born at 35 weeks gestation or more.

PMID- 29222091
TI  - Waste management, informal recycling, environmental pollution and public health.
AB  - With rapid population growth, especially in low-income and middle-income
      countries, the generation of waste is increasing at an unprecedented rate. For
      example, annual global waste arising from waste electrical and electronic
      equipment alone will have increased from 33.8 to 49.8 million tonnes between 2010
      and 2018. Despite incineration and other waste treatment techniques, landfill
      still dominates waste disposal in low-income and middle-income countries. There
      is usually insufficient funding for adequate waste management in these countries
      and uptake of more advanced waste treatment technologies is poor. Without proper
      management, many landfills represent serious hazards as typified by the landslide
      in Shenzhen, China on 20 December 2015. In addition to formal waste recycling
      systems, approximately 15million people around the world are involved in informal
      waste recycling, mainly for plastics, metals, glass and paper. This review
      examines emerging public health challenges, in particular within low-income and
      middle-income countries, associated with the informal sector. While informal
      recyclers contribute to waste recycling and reuse, the relatively primitive
      techniques they employ, combined with improper management of secondary
      pollutants, exacerbate environmental pollution of air, soil and water. Even
      worse, insufficient occupational health measures expose informal waste workers to
      a range of pollutants, injuries, respiratory and dermatological problems,
      infections and other serious health issues that contribute to low life
      expectancy. Integration of the informal sector with its formal counterparts could
      improve waste management while addressing these serious health and livelihood
      issues. Progress in this direction has already been made notably in several Latin
      American countries where integrating the informal and formal sectors has had a
      positive influence on both waste management and poverty alleviation.

PMID- 29222090
TI  - GPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility
      to intestinal damage.
AB  - Intraepithelial lymphocytes (IELs) of the small intestine are intimately
      associated with the epithelial cells. Yet, the factors controlling their
      migration and interaction dynamics are poorly understood. We demonstrate that
      GPR55, a receptor that mediates migration inhibition in response to
      lysophosphatidylinositol (LPI), negatively regulates T cell receptor gammadelta
      (TCRgammadelta) IEL accumulation in the small intestine. Intravital imaging
      studies show that GPR55-deficient IELs migrate faster and interact more
      extensively with epithelial cells. GPR55 also negatively regulates T cell homing
      to the small intestine and gammadeltaT cell egress from Peyer's patches. GPR55
      deficiency or short-term antagonist treatment protects from nonsteroidal anti
      inflammatory drug-induced increases in intestinal permeability. These findings
      identify a migration-inhibitory receptor that restrains IEL-epithelial cell cross
      talk and show that antagonism of this receptor can protect from intestinal
      barrier dysfunction.

PMID- 29222089
TI  - Core-binding factor beta and Runx transcription factors promote adaptive natural
      killer cell responses.
AB  - Natural killer (NK) cells are innate lymphocytes that have features of adaptive
      immunity such as clonal expansion and generation of long-lived memory.
      Interleukin-12 (IL-12) signaling through its downstream transcription factor
      signal transducer and activator of transcription 4 (STAT4) is required for the
      generation of memory NK cells after expansion. We identify gene loci that are
      highly enriched for STAT4 binding using chromatin immunoprecipitation sequencing
      for STAT4 and the permissive histone mark H3K4me3 in activated NK cells. We found
      that promoter regions of Runx1 and Runx3 are targets of STAT4 and that STAT4
      binding during NK cell activation induces epigenetic modifications of Runx gene
      loci resulting in increased expression. Furthermore, specific ablation of Runx1,
      Runx3, or their binding partner Cbfb in NK cells resulted in defective clonal
      expansion and memory formation during viral infection, with evidence for Runx1
      mediated control of a cell cycle program. Thus, our study reveals a mechanism
      whereby STAT4-mediated epigenetic control of individual Runx transcription
      factors promotes the adaptive behavior of antiviral NK cells.

PMID- 29222092
TI  - Targeted disruption of the Kcnj5 gene in the female mouse lowers aldosterone
      levels.
AB  - Aldosterone is released from adrenal zona glomerulosa (ZG) cells and plays an
      important role in Na and K homoeostasis. Mutations in the human inwardly
      rectifying K channel CNJ type (KCNJ) 5 (KCNJ5) gene encoding the G-coupled
      inwardly rectifying K channel 4 (GIRK4) cause abnormal aldosterone secretion and
      hypertension. To better understand the role of wild-type (WT) GIRK4 in regulating
      aldosterone release, we have looked at aldosterone secretion in a Kcnj5 knockout
      (KO) mouse. We found that female but not male KO mice have reduced aldosterone
      levels compared with WT female controls, but higher levels of aldosterone after
      angiotensin II (Ang-II) stimulation. These differences could not be explained by
      sex differences in aldosterone synthase (Cyp11B2) gene expression in the mouse
      adrenal. Using RNAseq analysis to compare WT and KO adrenals, we showed that
      females also have a much larger set of differentially expressed adrenal genes
      than males (395 compared with 7). Ingenuity Pathway Analysis (IPA) of this gene
      set suggested that peroxisome proliferator activated receptor (PPAR) nuclear
      receptors regulated aldosterone production and altered signalling in the female
      KO mouse, which could explain the reduced aldosterone secretion. We tested this
      hypothesis in H295R adrenal cells and showed that the selective PPARalpha agonist
      fenofibrate can stimulate aldosterone production and induce Cyp11b2. Dosing mice
      in vivo produced similar results. Together our data show that Kcnj5 is important
      for baseline aldosterone secretion, but its importance is sex-limited at least in
      the mouse. It also highlights a novel regulatory pathway for aldosterone
      secretion through PPARalpha that may have translational potential in human
      hyperaldosteronism.

PMID- 29222093
TI  - Are the NHS national outcomes frameworks past their sell-by date?

PMID- 29222094
TI  - Case-based discussion from the neonatal intensive care unit: a case of an
      intentional oesophageal intubation.
AB  - Tracheal agenesis (TA) is a rare congenital defect consisting of complete or
      partial absence of the trachea below the larynx. Antenatal diagnosis is
      challenging, and most cases are detected in the postnatal period. Airway
      management of such cases, particularly in the absence of antenatal diagnosis, can
      be challenging. Various methods of management have been described but with
      limited success, and overall prognosis remains very poor. We present an
      unexpected case of TA, highlighting management issues and diagnostic methods.

PMID- 29222095
TI  - NHS pays L45 000 to family of a woman who was kept alive against her will.

PMID- 29222096
TI  - Aerobic Transformation of 2,4-Dinitrotoluene by Escherichia coli and Its
      Implications for the Detection of Trace Explosives.
AB  - DNT (2,4-dinitrotoluene), a volatile impurity in military-grade 2,4,6
      trinitrotoluene (TNT)-based explosives, is a potential tracer for the detection
      of buried landmines and other explosive devices. We have previously described an
      Escherichia coli bioreporter strain engineered to detect traces of DNT and have
      demonstrated that the yqjF gene promoter, the sensing element of this
      bioreporter, is induced not by DNT but by at least one of its transformation
      products. In the present study, we have characterized the initial stages of DNT
      biotransformation in E. coli, have identified the key metabolic products in this
      reductive pathway, and demonstrate that the main DNT metabolite that induces yqjF
      is 2,4,5-trihydroxytoluene. We further show that E. coli cannot utilize DNT as a
      sole carbon or nitrogen source and propose that this compound is metabolized in
      order to neutralize its toxicity to the cells.IMPORTANCE The information provided
      in this article sheds new light both on the microbial biodegradability of
      nitroaromatic compounds and on the metabolic capabilities of E. coli By doing so,
      it also clarifies the pathway leading to the previously unexplained induction of
      the E. coli yqjF gene by 2,4-dinitrotoluene, an impurity that accompanies 2,4,6
      trinitrotoluene (TNT)-based explosives. Our improved understanding of these
      processes will serve to molecularly enhance the performance of a previously
      described microbial bioreporter of buried landmines and other explosive devices,
      in which the yqjF gene promoter serves as the sensing element.

PMID- 29222097
TI  - A New Niche for Anoxygenic Phototrophs as Endoliths.
AB  - Anoxygenic phototrophic bacteria (APBs) occur in a wide range of aquatic
      habitats, from hot springs to freshwater lakes and intertidal microbial mats.
      Here, we report the discovery of a novel niche for APBs: endoliths within marine
      littoral carbonates. In a study of 40 locations around Isla de Mona, Puerto Rico,
      and Menorca, Spain, 16S rRNA high-throughput sequencing of endolithic community
      DNA revealed the presence of abundant phylotypes potentially belonging to well
      known APB clades. An ad hoc phylogenetic classification of these sequences
      enabled us to refine the assignments more stringently. Even then, all locations
      contained such putative APBs, often reaching a significant proportion of all
      phototrophic sequences. In fact, in some 20% of samples, their contribution
      exceeded that of oxygenic phototrophs, previously regarded as the major type of
      endolithic microbe in carbonates. The communities contained representatives of
      APBs in the Chloroflexales, various proteobacterial groups, and Chlorobi The most
      abundant phylotypes varied with geography: on Isla de Mona, Roseiflexus and
      Chlorothrix-related phylotypes dominated, whereas those related to Erythrobacter
      were the most common in Menorca. The presence of active populations of APBs was
      corroborated through an analysis of photopigments: bacteriochlorophylls were
      detected in all samples, bacteriochlorophyll c and a being most abundant. We
      discuss the potential metabolism and geomicrobial roles of endolithic APBs.
      Phylogenetic inference suggests that APBs may be playing a role as
      photoheterotrophs, adding biogeochemical complexity to our understanding of such
      communities. Given the global extent of coastal carbonate platforms, they likely
      represent a very large and unexplored habitat for APBs.IMPORTANCE Endolithic
      microbial communities from carbonates, which have been explored for over 2
      centuries in predominantly naturalistic studies, were thought to be primarily
      composed of eukaryotic algae and cyanobacteria. Our report represents a paradigm
      shift in this regard, at least for the marine environment, demonstrating the
      presence of ubiquitous and abundant populations of APBs in this habitat. It
      raises questions about the role of these organisms in the geological dynamics of
      coastal carbonates, including coral reefs.

PMID- 29222098
TI  - Occurrence, Persistence, and Contamination Routes of Listeria monocytogenes
      Genotypes on Three Finnish Dairy Cattle Farms: a Longitudinal Study.
AB  - The molecular epidemiology of Listeria monocytogenes was investigated in a
      longitudinal study of three Finnish dairy farms during 2013 to 2016. A total of
      186 bulk tank milk (BTM), 224 milk filter sock (MFS), and 1,702 barn environment
      samples were analyzed, and isolates of L. monocytogenes were genotyped using
      pulsed-field gel electrophoresis. L. monocytogenes occurred throughout the year
      in all sample types, and the prevalence in MFS increased significantly during the
      indoor season. L. monocytogenes was more prevalent in MFS (29%) than in BTM (13%)
      samples. However, the prevalence of L. monocytogenes varied more between farms in
      samples of MFS (13 to 48%) than in BTM (10 to 16%). For each farm, the L.
      monocytogenes genotypes detected were classified by persistence (defined as
      persistent if isolated from >=3 samples during >=6 months) and predominance
      (defined as predominant if >5% prevalence on at least one farm visit). The
      prevalence of sporadic genotypes was 4 to 5% on all three farms. In contrast, the
      prevalence of persistent predominant genotypes varied between farms by 4% to 16%.
      The highest prevalence of persistent predominant genotypes was observed on the
      farm with the poorest production hygiene. Persistent predominant genotypes were
      most prevalent on feeding surfaces, water troughs, and floors. Genotypes isolated
      from the milking system or from cow udders had a greater relative risk of
      occurring in BTM and MFS than genotypes that only occurred elsewhere in the farm,
      supporting the hypothesis that L. monocytogenes is transmitted to milk from
      contamination on the udder surface or in the milking equipment.IMPORTANCEListeria
      monocytogenes is a ubiquitous environmental bacterium and the causative agent of
      a serious foodborne illness, listeriosis. Dairy products are common vehicles of
      listeriosis, and dairy cattle farms harbor L. monocytogenes genotypes associated
      with human listeriosis outbreaks. Indeed, dairy cattle farms act as a reservoir
      of L. monocytogenes, and the organism is frequently detected in bulk tank milk
      (BTM) and in the feces of clinically healthy cows. The ecology of L.
      monocytogenes in the farm environment is complex and poorly understood. Isolates
      of the same L. monocytogenes genotype can occur in the farm for years, but the
      factors contributing to the persistence of genotypes on dairy farms are unknown.
      Knowledge of the persistence patterns and contamination routes of L.
      monocytogenes on dairy farms can improve management of the contamination pressure
      in the farm environment and aid in the development of focused control strategies
      to reduce BTM contamination.

PMID- 29222099
TI  - Isolation of the (+)-Pinoresinol-Mineralizing Pseudomonas sp. Strain SG-MS2 and
      Elucidation of Its Catabolic Pathway.
AB  - Pinoresinol is a dimer of two beta-beta'-linked coniferyl alcohol molecules. It
      is both a plant defense molecule synthesized through the shikimic acid pathway
      and a representative of several beta-beta-linked dimers produced during the
      microbial degradation of lignin in dead plant material. Until now, little has
      been known about the bacterial catabolism of such dimers. Here we report the
      isolation of the efficient (+)-pinoresinol-mineralizing Pseudomonas sp. strain SG
      MS2 and its catabolic pathway. Degradation of pinoresinol in this strain is
      inducible and proceeds via a novel oxidative route, which is in contrast to the
      previously reported reductive transformation by other bacteria. Based on enzyme
      assays and bacterial growth, cell suspension, and resting cell studies, we
      provide conclusive evidence that pinoresinol degradation in strain SG-MS2 is
      initiated by benzylic hydroxylation, generating a hemiketal via a quinone methide
      intermediate, which is then hydrated at the benzylic carbon by water. The
      hemiketal, which stays in equilibrium with the corresponding keto alcohol,
      undergoes an aryl-alkyl cleavage to generate a lactone and 2-methoxyhydroquinone.
      While the fate of 2-methoxyhydroquinone is not investigated further, it is
      assumed to be assimilated by ring cleavage. The lactone is further metabolized
      via two routes, namely, lactone ring cleavage and benzylic hydroxylation via a
      quinone methide intermediate, as described above. The resulting hemiketal again
      exists in equilibrium with a keto alcohol. Our evidence suggests that both routes
      of lactone metabolism lead to vanillin and vanillic acid, which we show can then
      be mineralized by strain SG-MS2.IMPORTANCE The oxidative catabolism of (+)
      pinoresinol degradation elucidated here is fundamentally different from the
      reductive cometabolism reported for two previously characterized bacteria. Our
      findings open up new opportunities to use lignin for the biosynthesis of
      vanillin, a key flavoring agent in foods, beverages, and pharmaceuticals, as well
      as various new lactones. Our work also has implications for the study of new
      pinoresinol metabolites in human health. The enterodiol and enterolactone
      produced through reductive transformation of pinoresinol by gut microbes have
      already been associated with decreased risks of cancer and cardiovascular
      diseases. The metabolites from oxidative metabolism we find here also deserve
      attention in this respect.

PMID- 29222101
TI  - Divergence in gene regulation contributes to sympatric speciation of Shewanella
      baltica strains.
AB  - Niche partitioning and sequence evolution drive genomic and phenotypic
      divergence, which ultimately leads to bacterial diversification. This study
      investigated genomic composition of two Shewanella baltica clades previously
      identified through multi-locus sequencing typing and recovered from the redox
      transition zone in the central Baltic Sea. Comparative genomic analysis revealed
      significantly higher inter- than intra-clade genomic dissimilarity, and that a
      subset of genes present in Clade A were associated with potential adaptation to
      respiration of sulfur compounds present in the redox-transition zone.
      Transcriptomic divergence between two representative strains of Clades A and D,
      OS185 and OS195, was also characterized and revealed marked regulatory
      differences. We found that both transcriptional divergence of shared genes and
      expression of strain-specific genes lead to differences in regulatory patterns
      between strains that correlate with environmental redox niches. For instance,
      under anoxic conditions of respiratory nitrate ammonification, OS185 - the strain
      isolated from nitrate-rich environment, upregulated nearly twice the number of
      shared genes compared to OS195 - the strain isolated from H2S-containing anoxic
      environment. Conversely, OS195 showed stronger induction of strain-specific
      genes, especially those associated with sulfur compound respiration, under
      thiosulfate-reducing conditions. A positive association between the level of
      transcriptional divergence and sequence divergence for shared genes was also
      noted. Our results provide further support for the hypothesis that genomic
      changes impacting transcriptional regulation play an important role in the
      diversification of ecologically distinct populations.Importance This study
      examined potential mechanisms through which co-occurring Shewanella baltica
      strains diversified to form ecologically distinct populations. At the time of
      isolation, the strains studied composed the major fraction of culturable nitrate
      reducing communities in the Baltica Sea. Analysis of genomic content of 13 S.
      baltica strains from two clades representing different ecotypes demonstrated that
      one clade specifically possesses a number of genes that could favor successful
      adaptation to respire sulfur compounds in the portion of the water column from
      which these strains were isolated. In addition, transcriptional profiling of
      fully-sequenced strains representative of these two clades, OS185 and OS195,
      under oxygen-, nitrate- and thiosulfate-respiring conditions demonstrated that
      the strains exhibit relatively similar transcriptional responses during aerobic
      growth, but more distinct transcriptional responses under nitrate and thiosulfate
      respiring conditions. Results from this study provide insights into how genomic
      and gene regulatory diversification together impacted the redox specialization of
      the S. baltica strains.

PMID- 29222100
TI  - Lactococcus lactis Diversity in Undefined Mixed Dairy Starter Cultures as
      Revealed by Comparative Genome Analyses and Targeted Amplicon Sequencing of epsD.
AB  - Undefined mesophilic mixed (DL) starter cultures are used in the production of
      continental cheeses and contain unknown strain mixtures of Lactococcus lactis and
      leuconostocs. The choice of starter culture affects the taste, aroma, and quality
      of the final product. To gain insight into the diversity of Lactococcus lactis
      strains in starter cultures, we whole-genome sequenced 95 isolates from three
      different starter cultures. Pan-genomic analyses, which included 30 publically
      available complete genomes, grouped the strains into 21 L. lactis subsp. lactis
      and 28 L. lactis subsp. cremoris lineages. Only one of the 95 isolates grouped
      with previously sequenced strains, and the three starter cultures showed no
      overlap in lineage distributions. The culture diversity was assessed by targeted
      amplicon sequencing using purR, a core gene, and epsD, present in 93 of the 95
      starter culture isolates but absent in most of the reference strains. This
      enabled an unprecedented discrimination of starter culture Lactococcus lactis and
      revealed substantial differences between the three starter cultures and
      compositional shifts during the cultivation of cultures in milk.IMPORTANCE In
      contemporary cheese production, standardized frozen seed stock starter cultures
      are used to ensure production stability, reproducibility, and quality control of
      the product. The dairy industry experiences significant disruptions of cheese
      production due to phage attacks, and one commonly used countermeasure to phage
      attack is to employ a starter rotation strategy, in which two or more starters
      with minimal overlap in phage sensitivity are used alternately. A culture
      independent analysis of the lactococcal diversity in complex undefined starter
      cultures revealed large differences between the three starter cultures and
      temporal shifts in lactococcal composition during the production of bulk
      starters. A better understanding of the lactococcal diversity in starter cultures
      will enable the development of more robust starter cultures and assist in
      maintaining the efficiency and stability of the production process by ensuring
      the presence of key bacteria that are important to the characteristics of the
      product.

PMID- 29222102
TI  - Tracking the Taxonomy of the Genus Bifidobacterium Based on a Phylogenomic
      Approach.
AB  - For decades, bacterial taxonomy has been based on in vitro molecular biology
      techniques and comparison of molecular marker sequences to measure the degree of
      genetic similarity and deduce phylogenetic relatedness of novel bacterial species
      to reference microbial taxa. Due to the advent of the genomic era, access to
      complete bacterial genome contents has become easier, thereby presenting the
      opportunity to precisely investigate the overall genetic diversity of
      microorganisms. Here, we describe a high-accuracy phylogenomic approach to assess
      the taxonomy of members of the genus Bifidobacterium and identify apparent
      misclassifications in current bifidobacterial taxonomy. The developed method was
      validated by the classification of seven novel taxa belonging to the genus
      Bifidobacterium by employing their overall genetic content. The results of this
      study demonstrate the potential of this whole-genome approach to become the gold
      standard for phylogenomics-based taxonomic classification of bacteria.IMPORTANCE
      Nowadays, next-generation sequencing has given access to genome sequences of the
      currently known bacterial taxa. The public databases constructed by means of
      these new technologies allowed comparison of genome sequences between
      microorganisms, providing information to perform genomic, phylogenomic, and
      evolutionary analyses. In order to avoid misclassifications in the taxonomy of
      novel bacterial isolates, new (bifido)bacterial taxons should be validated with a
      phylogenomic assessment like the approach presented here.

PMID- 29222103
TI  - A Novel Nonantibiotic, lgt-Based Selection System for Stable Maintenance of
      Expression Vectors in Escherichia coli and Vibrio cholerae.
AB  - Antibiotic selection for the maintenance of expression plasmids is discouraged in
      the production of recombinant proteins for pharmaceutical or other human uses due
      to the risks of antibiotic residue contamination of the final products and the
      release of DNA encoding antibiotic resistance into the environment. We describe
      the construction of expression plasmids that are instead maintained by
      complementation of the lgt gene encoding a (pro)lipoprotein glyceryl transferase
      essential for the biosynthesis of bacterial lipoprotein. Mutations in lgt are
      lethal in Escherichia coli and other Gram-negative organisms. The lgt gene was
      deleted from E. coli and complemented by the Vibrio cholerae-derived gene
      provided in trans on a temperature-sensitive plasmid, allowing cells to grow at
      30 degrees C but not at 37 degrees C. A temperature-insensitive expression vector
      carrying the V. cholerae-derived lgt gene was constructed, whereby transformants
      were selected by growth at 39 degrees C. The vector was successfully used to
      express two recombinant proteins, one soluble and one forming insoluble inclusion
      bodies. Reciprocal construction was done by deleting the lgt gene from V.
      cholerae and complementing the lesion with the corresponding gene from E. coli
      The resulting strain was used to produce the secreted recombinant cholera toxin B
      subunit (CTB) protein, a component of licensed as well as newly developed oral
      cholera vaccines. Overall, the lgt system described here confers extreme
      stability on expression plasmids, and this strategy can be easily transferred to
      other Gram-negative species using the E. coli-derived lgt gene for
      complementation.IMPORTANCE Many recombinant proteins are produced in bacteria
      from genes carried on autonomously replicating DNA elements called plasmids.
      These plasmids are usually inherently unstable and rapidly lost. This can be
      prevented by using genes encoding antibiotic resistance. Plasmids are thus
      maintained by allowing only plasmid-containing cells to survive when the bacteria
      are grown in medium supplemented with antibiotics. In the described antibiotic
      free system for the production of recombinant proteins, an essential gene is
      deleted from the bacterial chromosome and instead provided on a plasmid. The loss
      of the plasmid becomes lethal for the bacteria. Such plasmids can be used for the
      expression of recombinant proteins. This broadly applicable system removes the
      need for antibiotics in recombinant protein production, thereby contributing to
      reducing the spread of genes encoding antibiotic resistance, reducing the release
      of antibiotics into the environment, and freeing the final products (often used
      in pharmaceuticals) from contamination with potentially harmful antibiotic
      residues.

PMID- 29222104
TI  - Effect of Start-Up Strategies and Electrode Materials on Carbon Dioxide Reduction
      on Biocathodes.
AB  - The enrichment of CO2-reducing microbial biocathodes is challenging. Previous
      research has shown that a promising approach could be to first enrich bioanodes
      and then lower the potential so the electrodes are converted into biocathodes.
      However, the effect of such a transition on the microbial community on the
      electrode has not been studied. The goal of this study was thus to compare the
      start-up of biocathodes from preenriched anodes with direct start-up from bare
      electrodes and to investigate changes in microbial community composition. The
      effect of three electrode materials on the long-term performance of the
      biocathodes was also investigated. In this study, preenrichment of acetate
      oxidizing bioanodes did not facilitate the start-up of biocathodes. It took about
      170 days for the preenriched electrodes to generate substantial cathodic current,
      compared to 83 days for the bare electrodes. Graphite foil and carbon felt
      cathodes produced higher current at the beginning of the experiment than did
      graphite rods. However, all electrodes produced similar current densities at the
      end of the over 1-year-long study (2.5 A/m2). Methane was the only product
      detected during operation of the biocathodes. Acetate was the only product
      detected after inhibition of the methanogens. Microbial community analysis showed
      that Geobacter sp. dominated the bioanodes. On the biocathodes, the Geobacter sp.
      was succeeded by Methanobacterium spp., which made up more than 80% of the
      population. After inhibition of the methanogens, Acetobacterium sp. became
      dominant on the electrodes (40% relative abundance). The results suggested that
      bioelectrochemically generated H2 acted as an electron donor for CO2
      reduction.IMPORTANCE In microbial electrochemical systems, living microorganisms
      function as catalysts for reactions on the anode and/or the cathode. There is a
      variety of potential applications, ranging from wastewater treatment and biogas
      generation to production of chemicals. Systems with biocathodes could be used to
      reduce CO2 to methane, acetate, or other high-value chemicals. The technique can
      be used to convert solar energy to chemicals. However, enriching biocathodes that
      are capable of CO2 reduction is more difficult and less studied than enriching
      bioanodes. The effect of different start-up strategies and electrode materials on
      the microbial communities that are enriched on biocathodes has not been studied.
      The purpose of this study was to investigate two different start-up strategies
      and three different electrode materials for start-up and long-term operation of
      biocathodes capable of reducing CO2 to valuable biochemicals.

PMID- 29222105
TI  - The Emergency Medical Service Microbiome.
AB  - Emergency medical services (EMS) personnel are an integral component of the
      healthcare framework and function to transport patients from various locations to
      and between care facilities. In addition to physical injury, EMS personnel are
      expected to be at high risk to acquire and transmit healthcare associated
      infections (HAIs) in the workplace. However, currently little is known about EMS
      biosafety risk factors and the epidemiological contribution of EMS to pathogen
      transmission within and outside of the healthcare sector. Our review summarizes
      literature surrounding pathogen prevalence and decontamination strategies in EMS
      as a basis for understanding biosafety risks in the EMS environment. We conclude
      that additional studies are needed to investigate pathogen prevalence worldwide
      and create evidence-based guidelines for decontamination. Finally, we discuss
      emerging DNA sequencing technologies and other methods that can be applied to
      characterize and mitigate EMS biosafety risks in the future.ImportanceHealthcare
      facility microbiomes contain diverse bacterial, fungal and viral pathogens that
      cause over 1.7 million healthcare-associated infections (HAIs) each year in the
      United States alone. While hospital microbiomes have been relatively well
      studied, little is known about emergency medical services (EMS) infrastructure
      and equipment microbiomes or the role(s) they play in HAI transmission between
      healthcare facilities. We review recent literature investigating the microbiome
      of ambulances and other EMS service facilities which consistently identify
      antibiotic-resistant pathogens causing HAIs, including methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, and Klebsiella
      pneumoniae Our review provides evidence that EMS microbiomes are dynamic but
      important pathogen reservoirs and underscores the need for more wide-spread and
      in-depth microbiome studies to elucidate patterns of pathogen transmission.
      Understanding the complex interplay between EMS and hospital microbiomes will
      provide key insights into pathogen transmission mechanisms and identify
      strategies to minimize HAIs and community infection.

PMID- 29222106
TI  - PSMA brings new flavors to PI3K signaling: A role for glutamate in prostate
      cancer.
AB  - In this issue of JEM, Kaittanis et al. (https://doi.org/10.1084/jem.20171052)
      report a new signaling role for prostate-specific membrane antigen (PSMA),
      providing a mechanistic link between two major oncogenic pathways, as well as
      promising therapeutic implications for the diagnosis and treatment of prostate
      cancer.

PMID- 29222108
TI  - Illicit cigarette sales in Indian cities: findings from a retail survey.
AB  - OBJECTIVE: To estimate illicit cigarette consumption in India using a modified
      and replicable method and compare it with estimates generated by the tobacco
      industry and by a commercial entity. METHODS: The study employed a modified
      approach to cigarette pack analysis suitable for countries with prevalent single
      cigarette sales. Empty cigarette packs generated by 1 day's single-cigarette
      sales were collected directly from cigarette vendors in four large and four small
      cities covering the length and breadth of India. Ten areas were randomly selected
      in each city/town, and all shops selling cigarettes within 1 km of the central
      point were surveyed. A cigarette pack was classified as illicit if it had at
      least one of the following attributes: (a) a duty-free sign; (b) no graphic
      health warnings; (c) no textual health warnings; or (d) no mention of 'price
      inclusive of all taxes' or similar text. FINDINGS: We collected 11 063 empty
      cigarette packs from 1727 retailers, and 2.73% of them were classified as
      illicit. The estimates varied substantially across locations with the highest
      prevalence of illicit packs in the town of Aizawl near the Bangladesh and Myanmar
      border (35.87%). The share of illicit cigarettes was found to be much higher
      (13.77%) among the cheapest cigarette brands. Illicit cigarettes are primarily
      distributed via formal stores rather than informal tea/pan shops. CONCLUSION: Our
      estimate of the illicit cigarette market share of 2.73% casts serious doubt on
      the tobacco industry estimate of 20% and Euromonitor's estimate of 21.3%.

PMID- 29222107
TI  - IL-33 promotes the egress of group 2 innate lymphoid cells from the bone marrow.
AB  - Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and
      key participants in type 2 immune responses in the context of allergic
      inflammation and infection. ILC2s develop in the bone marrow from common lymphoid
      progenitor cells, but little is known about how ILC2s egress from the bone marrow
      for hematogenous trafficking. In this study, we identified a critical role for IL
      33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of
      ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal
      development of ILC2s but retained significantly more ILC2 progenitors in the bone
      marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or
      pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone
      marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis
      mouse model of tissue disruption and repopulation. Collectively, these data
      demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the
      bone marrow.

PMID- 29222109
TI  - MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell
      substrate contacts in epithelial cells.
AB  - Treatment of epithelial cells with interferon-gamma and TNF-alpha (IFN/TNF)
      results in increased paracellular permeability. To identify relevant proteins
      mediating barrier disruption, we performed proximity-dependent biotinylation
      (BioID) of occludin and found that tagging of MARCKS-related protein (MRP; also
      known as MARCKSL1) increased ~20-fold following IFN/TNF administration. GFP-MRP
      was focused at the lateral cell membrane and its overexpression potentiated the
      physiological response of the tight junction barrier to cytokines. However,
      deletion of MRP did not abrogate the cytokine responses, suggesting that MRP is
      not required in the occludin-dependent IFN/TNF response. Instead, our results
      reveal a key role for MRP in epithelial cells in control of multiple actin-based
      structures, likely by regulation of integrin signaling. Changes in focal adhesion
      organization and basal actin stress fibers in MRP-knockout (KO) cells were
      reminiscent of those seen in FAK-KO cells. In addition, we found alterations in
      cell-cell interactions in MRP-KO cells associated with increased junctional
      tension, suggesting that MRP may play a role in focal adhesion-adherens junction
      cross talk. Together, our results are consistent with a key role for MRP in
      cytoskeletal organization of cell contacts in epithelial cells.

PMID- 29222110
TI  - A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1epsilon.
AB  - Casein kinase 1 (CK1) plays central roles in various signal transduction pathways
      and performs many cellular activities. For many years CK1 was thought to act
      independently of modulatory subunits and in a constitutive manner. Recently, DEAD
      box RNA helicases, in particular DEAD box RNA helicase 3 X-linked (DDX3X), were
      found to stimulate CK1 activity in vitro In order to observe CK1 activity in
      living cells and to study its interaction with DDX3X, we developed a CK1-specific
      FRET biosensor. This tool revealed that DDX3X is indeed required for full CK1
      activity in living cells. Two counteracting mechanisms control the activity of
      these enzymes. Phosphorylation by CK1 impairs the ATPase activity of DDX3X and
      RNA destabilizes the DDX3X-CK1 complex. We identified possible sites of
      interaction between DDX3X and CK1. While mutations identified in the DDX3X genes
      of human medulloblastoma patients can enhance CK1 activity in living cells, the
      mechanism of CK1 activation by DDX3X points to a possible therapeutic approach in
      CK1-related diseases such as those caused by tumors driven by aberrant Wnt/beta
      catenin and Sonic hedgehog (SHH) activation. Indeed, CK1 peptides can reduce CK1
      activity.

PMID- 29222112
TI  - Rheb localized on the Golgi membrane activates lysosome-localized mTORC1 at the
      Golgi-lysosome contact site.
AB  - In response to amino acid supply, mTORC1, a master regulator of cell growth, is
      recruited to the lysosome and activated by the small GTPase Rheb. However, the
      intracellular localization of Rheb is controversial. In this study, we showed
      that a significant portion of Rheb is localized on the Golgi but not on the
      lysosome. GFP-Rheb could activate mTORC1, even when forced to exclusively
      localize to the Golgi. Likewise, artificial recruitment of mTORC1 to the Golgi
      allowed its activation. Accordingly, the Golgi was in contact with the lysosome
      at an newly discovered area of the cell that we term the Golgi-lysosome contact
      site (GLCS). The number of GLCSs increased in response to amino acid supply,
      whereas GLCS perturbation suppressed mTORC1 activation. These results suggest
      that inter-organelle communication between the Golgi and lysosome is important
      for mTORC1 regulation and the Golgi-localized Rheb may activate mTORC1 at GLCSs.

PMID- 29222111
TI  - Rap1B promotes VEGF-induced endothelial permeability and is required for dynamic
      regulation of the endothelial barrier.
AB  - Vascular endothelial growth factor (VEGF), a key angiogenic and permeability
      factor, plays an important role in new blood vessel formation. However, abnormal
      VEGF-induced VEGFR2 signaling leads to hyperpermeability. We have shown
      previously that Rap1, best known for promoting cell adhesion and vessel
      stability, is a critical regulator of VEGFR2-mediated angiogenic and shear-stress
      EC responses. To determine the role of Rap1 role in endothelial barrier dynamics,
      we examined vascular permeability in EC-specific Rap1A- and Rap1B-knockout mice,
      cell-cell junction remodeling and EC monolayer resistivity in Rap1-deficient ECs
      under basal, inflammatory or elevated VEGF conditions. Deletion of either Rap1
      isoform impaired de novo adherens junction (AJ) formation and recovery from LPS
      induced barrier disruption in vivo However, only Rap1A deficiency increased
      permeability in ECs and lung vessels. Interestingly, Rap1B deficiency attenuated
      VEGF-induced permeability in vivo and AJ remodeling in vitro Therefore, only
      Rap1A is required for the maintenance of normal vascular integrity. Importantly,
      Rap1B is the primary isoform essential for normal VEGF-induced EC barrier
      dissolution. Deletion of either Rap1 isoform protected against hyper permeability
      in the STZ-induced diabetes model, suggesting clinical implications for targeting
      Rap1 in pathologies with VEGF-induced hyperpermeability.

PMID- 29222113
TI  - The tail domain of the Aspergillus fumigatus class V myosin MyoE orchestrates
      septal localization and hyphal growth.
AB  - Myosins are critical motor proteins that contribute to the secretory pathway,
      polarized growth, and cytokinesis. The globular tail domains of class V myosins
      have been shown to be important for cargo binding and actin cable organization.
      Additionally, phosphorylation plays a role in class V myosin cargo choice. Our
      previous studies on the class V myosin MyoE in the fungal pathogen Aspergillus
      fumigatus confirmed its requirement for normal morphology and virulence. However,
      the domains and molecular mechanisms governing the functions of MyoE remain
      unknown. Here, by analyzing tail mutants, we demonstrate that the tail is
      required for radial growth, conidiation, septation frequency and MyoE's location
      at the septum. Furthermore, MyoE is phosphorylated at multiple residues in vivo;
      however, alanine substitution mutants revealed that no single phosphorylated
      residue was critical. Importantly, in the absence of the phosphatase calcineurin,
      an additional residue was phosphorylated in its tail domain. Mutation of this
      tail residue led to mislocalization of MyoE from the septa. This work reveals the
      importance of the MyoE tail domain and its phosphorylation/dephosphorylation in
      the growth and morphology of A. fumigatus.

PMID- 29222115
TI  - The methyltransferase SET9 regulates TGFB1 activation of renal fibroblasts via
      interaction with SMAD3.
AB  - Chronic kidney disease (CKD) is a global socioeconomic problem. It is
      characterised by the presence of differentiated myofibroblasts, which cause
      tissue fibrosis in response to TGFB1, leading to renal failure. Here, we define a
      novel interaction between the SET9 lysine methyltransferase (also known as SETD7)
      and SMAD3, the principal mediator of TGFB1 signalling in myofibroblasts. We show
      that SET9-deficient fibroblasts exhibit globally altered gene expression profiles
      in response to TGFB1, whilst overexpression of SET9 enhances SMAD3
      transcriptional activity. We also show that SET9 facilitates nuclear import of
      SMAD3 and controls SMAD3 protein degradation via ubiquitylation. On a cellular
      level, we demonstrate that SET9 is broadly required for the effects of TGFB1 in
      diseased primary renal fibroblasts; SET9 promotes fibroblast migration into
      wounds, expression of extracellular matrix proteins, collagen contractility and
      myofibroblast differentiation. Finally, we demonstrate that SET9 is recruited to
      the alpha-smooth muscle actin gene in response to TGFB1, providing a mechanism by
      which SET9 regulates myofibroblast contractility and differentiation. Together
      with previous studies, we make the case for SET9 inhibition in the treatment of
      progressive CKD.

PMID- 29222114
TI  - Blood vitronectin is a major activator of LIF and IL-6 in the brain through
      integrin-FAK and uPAR signaling.
AB  - We defined how blood-derived vitronectin (VTN) rapidly and potently activates
      leukemia inhibitory factor (LIF) and pro-inflammatory interleukin 6 (IL-6) in
      vitro and after vascular injury in the brain. Treatment with VTN (but not
      fibrinogen, fibronectin, laminin-111 or collagen-I) substantially increased LIF
      and IL-6 within 4 h in C6-astroglioma cells, while VTN-/- mouse plasma was less
      effective than that from wild-type mice. LIF and IL-6 were induced by
      intracerebral injection of recombinant human (rh)VTN in mice, but induction seen
      upon intracerebral hemorrhage was less in VTN-/- mice than in wild-type
      littermates. In vitro, VTN effects were inhibited by RGD, alphavbeta3 and
      alphavbeta5 integrin-blocking peptides and antibodies. VTN activated focal
      adhesion kinase (FAK; also known as PTK2), whereas pharmacological- or siRNA
      mediated inhibition of FAK, but not PYK2, reduced the expression of LIF and IL-6
      in C6 and endothelial cells and after traumatic cell injury. Dominant-negative
      FAK (Y397F) reduced the amount of injury-induced LIF and IL-6. Pharmacological
      inhibition or knockdown of uPAR (also known as PLAUR), which binds VTN, also
      reduced cytokine expression, possibly through a common target of uPAR and
      integrins. We propose that VTN leakage into tissues promotes inflammation.
      Integrin-FAK signaling is therefore a novel IL-6 and LIF regulation mechanism
      relevant to the inflammation and stem cell fields.

PMID- 29222116
TI  - Our views of dynamic N6-methyladenosine RNA methylation.

PMID- 29222117
TI  - Pre-mRNA processing includes N6 methylation of adenosine residues that are
      retained in mRNA exons and the fallacy of "RNA epigenetics".
AB  - By using a cell fraction technique that separates chromatin-associated nascent
      RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown in a
      previous study that residues in exons are methylated (m6A) in nascent pre-mRNA
      and remain methylated in the same exonic residues in nucleoplasmic and
      cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of
      demethylation in mRNA exons that would correspond to so-called "epigenetic"
      demethylation. The turnover rate of mRNA molecules is faster, depending on m6A
      content in HeLa cell mRNA, suggesting that specification of mRNA stability may be
      the major role of m6A exon modification. In mouse embryonic stem cells (mESCs)
      lacking Mettl3, the major mRNA methylase, the cells continue to grow, making the
      same mRNAs with unchanged splicing profiles in the absence (>90%) of m6A in mRNA,
      suggesting no common obligatory role of m6A in splicing. All these data argue
      strongly against a commonly used "reversible dynamic methylation/demethylation"
      of mRNA, calling into question the concept of "RNA epigenetics" that parallels
      the well-established role of dynamic DNA epigenetics.

PMID- 29222120
TI  - Targeting Cardiovascular Implant Infection: Multimodality and Molecular Imaging.
AB  - Owing to their success in clinical practice, the prevalence of cardiovascular
      implants is continuously increasing. Implant infection is a relevant complication
      but remains a diagnostic challenge because echocardiography as a first-line test
      may be limited. Accordingly, a multimodality approach is increasingly used for
      diagnostic workup and supported by recent guidelines. As reviewed here, computed
      tomography and nuclear imaging provide incremental diagnostic value and may be
      combined in a single hybrid imaging session using positron emission
      tomography/computed tomography or single photon emission computed
      tomography/computed tomography. Molecular or cellular imaging helps to overcome
      the limitations of morphological imaging in implants. Larger-scale clinical
      studies, earlier application in the time course of diagnosis, monitoring of
      therapy success, technical advances, and novel radiopharmaceuticals will all
      contribute to sustained growth of advanced infection-targeted imaging in
      cardiovascular medicine.

PMID- 29222118
TI  - Purine- and pyrimidine-triple-helix-forming oligonucleotides recognize
      qualitatively different target sites at the ribosomal DNA locus.
AB  - Triplexes are noncanonical DNA structures, which are functionally associated with
      regulation of gene expression through ncRNA targeting to chromatin. Based on the
      rules of Hoogsteen base-pairing, polypurine sequences of a duplex can potentially
      form triplex structures with single-stranded oligonucleotides. Prediction of
      triplex-forming sequences by bioinformatics analyses have revealed enrichment of
      potential triplex targeting sites (TTS) at regulatory elements, mainly in
      promoters and enhancers, suggesting a potential function of RNA-DNA triplexes in
      transcriptional regulation. Here, we have quantitatively evaluated the potential
      of different sequences of human and mouse ribosomal RNA genes (rDNA) to form
      triplexes at different salt and pH conditions. We show by biochemical and
      biophysical approaches that some of these predicted sequences form triplexes with
      high affinity, following the canonical rules for triplex formation. We further
      show that RNA triplex-forming oligos (TFOs) are more stable than their DNA
      counterpart, and point mutations strongly affect triplex formation. We further
      show differential sequence requirements of pyrimidine and purine TFO sequences
      for efficient binding, depending on the G-C content of the TTS. The unexpected
      sequence specificity, revealing distinct sequence requirements for purine and
      pyrimidine TFOs, shows that in addition to the Hoogsteen pairing rules, a
      sequence code and mutations have to be taken into account to predict genomic TTS.

PMID- 29222121
TI  - Postoperative Reverse Remodeling and Symptomatic Improvement in Normal-Flow Low
      Gradient Aortic Stenosis After Aortic Valve Replacement.
AB  - BACKGROUND: Severe aortic stenosis (AS) most often presents with reduced aortic
      valve area (<1 cm2), normal stroke volume index (>=35 mL/m2), and either high
      mean gradient (>=40 mm Hg; normal-flow high-gradient AS) or low mean gradient
      (normal-flow low-gradient [NFLG] AS). The benefit of aortic valve replacement
      (AVR) among NFLG patients is controversial. We compared the impact of NFLG
      condition on preoperative left ventricular (LV) remodeling and myocardial
      fibrosis and postoperative remodeling and symptomatic benefit. METHODS AND
      RESULTS: Eighty-seven consecutive patients with reduced aortic valve area and
      normal stroke volume index undergoing AVR underwent echocardiography, magnetic
      resonance imaging, a 6-minute walk test, and measurement of natriuretic peptides
      before and 1 year after AVR. Myocardial fibrosis was assessed from magnetic
      resonance imaging. Patients were stratified as NFLG or normal-flow high-gradient.
      In total, 33 patients (38%) had NFLG. Before AVR, they were characterized by
      similar symptom burden but less severe AS measured by aortic valve area index
      (0.50+/-0.09 versus 0.40+/-0.08 cm2/m2; P<0.0001), lower LV mass index (74+/-18
      versus 90+/-26 g/m2; P=0.01), but the same degree of myocardial fibrosis. After
      AVR, NFLG had a smaller reduction in LV mass index (-3+/-10 versus -+/-18 g/m2;
      P<0.0001) and a smaller reduction in natriuretic peptides. Both groups
      experienced similar symptomatic improvement. Normal-flow high-gradient condition
      independently predicted change in LV mass index. CONCLUSIONS: Patients with NFLG
      had less severe AS and LV remodeling than patients with normal-flow high
      gradient. Furthermore, NFLG patients experienced less reverse remodeling but the
      same symptomatic benefit. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02316587.

PMID- 29222123
TI  - Abdominal Aorta Dilatation and Cardiovascular Outcomes: Another Dimension of
      Arterial Age?

PMID- 29222122
TI  - Increased Aortic Diameters on Multidetector Computed Tomographic Scan Are
      Independent Predictors of Incident Adverse Cardiovascular Events: The Framingham
      Heart Study.
AB  - BACKGROUND: Adverse aortic remodeling, such as dilation, is associated with
      multiple cardiovascular disease (CVD) risk factors. We sought to determine
      whether measures of enlarged aortic diameters improve prediction of incident
      adverse CVD events above standard CVD risk factors in a community-dwelling
      cohort. METHODS AND RESULTS: Participants from the Framingham Offspring and Third
      Generation Cohorts (n=3318; aged 48.9+/-10.3 years), who underwent noncontrast
      thoracic and abdominal multidetector computed tomography during 2002 to 2005, had
      complete risk factor profiles, and were free of clinical CVD, were included in
      this study. Diameters were measured at 4 anatomically defined locations: the
      ascending thoracic aorta, descending thoracic aorta, the infrarenal abdominal
      aorta, and lower abdominal aorta. Adverse events comprised CVD death, myocardial
      infarction, coronary insufficiency, index admission for heart failure, and
      stroke. Each aortic segment was dichotomized as enlarged (diameter >=upper 90th
      percentile for age, sex, and body surface area) or not enlarged; the hazard of an
      adverse event for an enlarged segment was determined using multivariable-adjusted
      Cox proportional hazards models. Over a mean 8.8+/-2.0 years of follow-up, there
      were 177 incident adverse CVD events. In models adjusted for traditional CVD risk
      factors, enlarged infrarenal abdominal aorta (hazard ratio=1.57; 95% confidence
      interval=1.06 to 2.32) and lower abdominal aorta (hazard ratio=1.53; 95%
      confidence interval=1.00 to 2.34) were associated with an increased hazard of CVD
      events. Enlarged ascending thoracic aorta and descending thoracic aorta were not
      significantly associated with CVD events. CONCLUSIONS: Among community-dwelling
      adults initially free of clinical CVD, enlarged infrarenal abdominal aorta and
      lower abdominal aorta, on noncontrast multidetector computed tomography scans,
      are independent predictors of incident adverse CVD events above traditional risk
      factors alone.

PMID- 29222124
TI  - Assessment of Normal-Flow Aortic Stenosis: Delving Too Deep?

PMID- 29222125
TI  - GMC begins High Court appeal over suspension of paediatrician convicted of
      manslaughter.

PMID- 29222126
TI  - Autoimmune CRMP5 neuropathy phenotype and outcome defined from 105 cases.
AB  - OBJECTIVE: To establish the phenotype and clinical outcomes of collapsin response
      mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal
      nuclear antibody type 1 (ANNA1)-immunoglobulin G (IgG) neuropathy. METHODS:
      Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line
      testing, and medical records were reviewed. RESULTS: One hundred five patients
      with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small
      cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1
      IgG neuropathy, 27 with coexisting CRMP5-IgG. Patients with CRMP5 had painful
      axonal polyradiculoneuropathy (65%), mostly asymmetric onset (84%), with
      neuropathy predating cancer diagnosis by 185 days (range 60-540 days). Most cases
      (79%) had moderate to severe neuropathic pain, all on neuropathic medications
      (median 2, range 1-4), opioids in 39%. Nerve biopsies (n = 2) showed
      microvascular inflammation with axonal degeneration. Compared to ANNA1 alone,
      CRMP5 neuropathy has a higher prevalence of pain (79% vs 46%, p = 0.008),
      asymmetric polyradiculoneuropathy (54% vs 12%, p < 0.001), and inflammatory
      spinal fluids (elevated CSF protein or nucleated cell count 92% vs 60%, p =
      0.022). Cerebellar ataxia (21%), myelopathy (19%), and optic neuritis and/or
      retinitis (11%) were common neurologic accompaniments. CRMP5 cases had
      significant pain reduction by immunotherapy (p < 0.001). Specifically, high-dose
      corticosteroid administration was associated with improvement/stabilization in
      neuropathy impairment scores (p = 0.012) (Class IV). Patients with CRMP5 had
      better 5-year survival than patients with ANNA1 (67% vs 32%, p = 0.012).
      CONCLUSION: Painful axonal asymmetric polyradiculoneuropathy is established as
      the major CRMP5 autoimmune neuropathy presentation and is distinguishable from
      other paraneoplastic neuropathies, including by ANNA1 autoimmunity. Patients with
      this phenotype should be prompted for CRMP5-IgG testing to assist in early cancer
      diagnosis.

PMID- 29222127
TI  - Unilateral periodic pupillary constriction causing alternating anisocoria.

PMID- 29222128
TI  - Directionality of nose-emitted echolocation calls from bats without a nose leaf
      (Plecotus auritus).
AB  - All echolocating bats and whales measured to date emit a directional bio-sonar
      beam that affords them a number of advantages over an omni-directional beam, i.e.
      reduced clutter, increased source level and inherent directional information. In
      this study, we investigated the importance of directional sound emission for
      navigation through echolocation by measuring the sonar beam of brown long-eared
      bats, Plecotus auritusPlecotus auritus emits sound through the nostrils but has
      no external appendages to readily facilitate a directional sound emission as
      found in most nose emitters. The study shows that P. auritus, despite lacking an
      external focusing apparatus, emits a directional echolocation beam (directivity
      index=13 dB) and that the beam is more directional vertically (-6 dB angle at 22
      deg) than horizontally (-6 dB angle at 35 deg). Using a simple numerical model,
      we found that the recorded emission pattern is achievable if P. auritus emits
      sound through the nostrils as well as the mouth. The study thus supports the
      hypothesis that a directional echolocation beam is important for perception
      through echolocation and we propose that animals with similarly non-directional
      emitter characteristics may facilitate a directional sound emission by emitting
      sound through both the nostrils and the mouth.

PMID- 29222129
TI  - Visual associative learning in wood ants.
AB  - Wood ants are a model system for studying visual learning and navigation. They
      can forage for food and navigate to their nests effectively by forming memories
      of visual features in their surrounding environment. Previous studies of freely
      behaving ants have revealed many of the behavioural strategies and environmental
      features necessary for successful navigation. However, little is known about the
      exact visual properties of the environment that animals learn or the neural
      mechanisms that allow them to achieve this. As a first step towards addressing
      this, we developed a classical conditioning paradigm for visual learning in
      harnessed wood ants that allows us to control precisely the learned visual cues.
      In this paradigm, ants are fixed and presented with a visual cue paired with an
      appetitive sugar reward. Using this paradigm, we found that visual cues learnt by
      wood ants through Pavlovian conditioning are retained for at least 1 h.
      Furthermore, we found that memory retention is dependent upon the ants'
      performance during training. Our study provides the first evidence that wood ants
      can form visual associative memories when restrained. This classical conditioning
      paradigm has the potential to permit detailed analysis of the dynamics of memory
      formation and retention, and the neural basis of learning in wood ants.

PMID- 29222131
TI  - Low-Dose Anthracycline and Risk of Heart Failure in a Pharmacokinetic Model of
      Human Myocardium Exposure: Analog Specificity and Role of Secondary Alcohol
      Metabolites.
AB  - Cumulative doses of doxorubicin and other antitumor anthracyclines may cause
      heart failure (HF). Cardiotoxicity is determined by cardiac exposure to
      anthracyclines and to more toxic secondary alcohol metabolites that are formed
      inside cardiomyocytes or diffuse from the bloodstream. Concerns exist that HF
      might be caused by cumulative anthracycline doses that were thought to be safe.
      Patients with gain-of-function polymorphism of carbonyl reductase 3 (CBR3), which
      converts anthracyclines to secondary alcohol metabolites, would be at a higher
      risk of HF. Recently, a pharmacokinetic model was developed that simulated
      clinical exposure of human myocardium to anthracyclines and incorporated
      simulations of CBR3 polymorphism. It was shown that HF risk could occur after
      lower doxorubicin doses than previously reported, particularly for patients with
      CBR3 polymorphism. In this study, we show that also daunorubicin and idarubicin,
      but not epirubicin, might cause HF after reportedly safe cumulative doses. CBR3
      polymorphism increased HF risk from daunorubicin and idarubicin to a greater
      extent as compared with doxorubicin. This was caused by daunorubicin and
      idarubicin forming higher levels of toxic metabolites in human myocardium;
      moreover, daunorubicin and idarubicin metabolites diffused from plasma and
      accumulated in cardiac tissue, whereas doxorubicin metabolite did not. CBR3
      polymorphism did not aggravate HF risk from epirubicin, which was caused by the
      very low levels of formation of its toxic metabolite. These results support
      concerns about HF risk from low-dose anthracycline, characterize the analog
      specificity of HF risk, and illuminate the role of secondary alcohol metabolites.

PMID- 29222130
TI  - Stargazin and cornichon-3 relieve polyamine block of AMPA receptors by enhancing
      blocker permeation.
AB  - Most ligand- and voltage-gated ion channels assemble as signaling complexes
      consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA
      type ionotropic glutamate receptors (AMPARs) coassemble with several families of
      auxiliary subunits that regulate channel gating as well as ion channel block and
      permeation. Previous work has shown that auxiliary proteins stargazin (or gamma2)
      and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of
      AMPARs, although the underlying mechanism has yet to be established. Here, we
      show that gamma2 and CNIH-3 relieve channel block by enhancing the rate of
      blocker permeation. Surprisingly, the relative permeability of the polyamine
      spermine (Spm) through the pore of the AMPAR-gamma2 or -CNIH-3 complexes is
      considerably more than AMPARs expressed alone. Spm permeability is comparable to
      that of Na+ for the GluA2-gamma2 complex and four times greater than Na+ with
      GluA2 + CNIH-3. A modified model of permeant channel block fully accounts for
      both the voltage- and time-dependent nature of Spm block. Estimates of block rate
      constants reveal that auxiliary subunits do not attenuate block by shifting the
      location of the block site within the membrane electric field, and they do not
      affect the blocker's ability to reach it. Instead, gamma2 and CNIH-3 relieve
      channel block by facilitating the blocker's exit rates from the open channel.
      From a physiological perspective, the relief of channel block exerted by gamma2
      and CNIH-3 ensures that there is unfettered signaling by AMPARs at glutamatergic
      synapses. Moreover, the pronounced ability of AMPARs to transport polyamines may
      have an unexpected role in regulating cellular polyamine levels.

PMID- 29222132
TI  - Invasive Assessment of the Coronary Microvasculature: The Index of
      Microcirculatory Resistance.
AB  - Traditionally, invasive coronary physiological assessment has focused on the
      epicardial coronary artery. More recently, appreciation of the importance of the
      coronary microvasculature in determining patient outcomes has grown. Several
      invasive modalities for interrogating microvascular function have been proposed.
      Angiographic techniques have been limited by their qualitative and subjective
      nature. Doppler wire-derived coronary flow reserve has been applied in research
      studies, but its clinical role has been limited by its lack of reproducibility,
      its lack of a clear normal value, and the fact that it is not specific for the
      microvasculature but interrogates the entire coronary circulation. The index of
      microcirculatory resistance-a thermodilution-derived measure of the minimum
      achievable microvascular resistance-is relatively easy to measure, more
      reproducible, has a clearer normal value, and is independent of epicardial
      coronary artery stenosis. The index of microcirculatory resistance has been shown
      to have prognostic value in patients with ST-segment-elevation myocardial
      infarction and cardiac allograft vasculopathy after heart transplantation.
      Emerging data demonstrate its role in evaluating patients with chest pain and
      nonobstructive coronary artery disease. Increasingly, the index of
      microcirculatory resistance is used as a reference standard for invasively
      assessing the microvasculature in clinical trials.

PMID- 29222133
TI  - GDF-15 (Growth Differentiation Factor 15) Is Associated With Lack of Ventricular
      Recovery and Mortality After Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND: Recent data suggest that circulating biomarkers may predict outcome
      in patients undergoing transcatheter aortic valve replacement (TAVR). We examined
      the association between inflammatory, myocardial, and renal biomarkers and their
      role in ventricular recovery and outcome after TAVR. METHODS AND RESULTS: A total
      of 112 subjects undergoing TAVR were included in the prospective registry. Plasma
      levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP
      (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin
      3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched
      healthy controls. Among echocardiographic parameters, we measured global
      longitudinal strain, indexed left ventricular mass, and indexed left atrial
      volume. The TAVR group included 59% male, with an average age of 84 years, and 1
      year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly
      associated with all-cause mortality (P<0.001). Inclusion of GDF-15 and CRP to the
      Society of Thoracic Surgeons score significantly improved C index (0.65-0.79;
      P<0.05) and provided a category-free net reclassification improvement of 106% at
      2 years (P=0.01). Among survivors, functional recovery in global longitudinal
      strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1
      year occurred in 48% and 22%, respectively. On multivariate logistic regression,
      lower baseline GDF-15 was associated with improved global longitudinal strain at
      1 year (hazard ratio=0.29; P<0.001). Furthermore, improvement in global
      longitudinal strain at 1 month correlated with lower overall mortality (hazard
      ratio=0.45; P=0.03). CONCLUSIONS: Elevated GDF-15 correlates with lack of reverse
      remodeling and increased mortality after TAVR and improves risk prediction of
      mortality when added to the Society of Thoracic Surgeons score.

PMID- 29222135
TI  - Ambulatory versus inpatient management of severe nausea and vomiting of
      pregnancy: a randomised control trial with patient preference arm.
AB  - OBJECTIVE: To determine whether ambulatory (outpatient (OP)) treatment of severe
      nausea and vomiting of pregnancy (NVP) is as effective as inpatient (IP) care.
      DESIGN: Non-blinded randomised control trial (RCT) with patient preference arm.
      SETTING: Two multicentre teaching hospitals in London. PARTICIPANTS: Women less
      than 20 weeks' pregnant with severe NVP and associated ketonuria (>1+). METHODS:
      Women who agreed to the RCT were randomised via web-based application to either
      ambulatory or IP treatment. Women who declined randomisation underwent the
      treatment of their choice in the patient preference trial (PPT) arm. Treatment
      protocols, data collection and follow-up were the same for all participants. MAIN
      OUTCOME MEASURES: Primary outcome was reduction in Pregnancy Unique
      Quantification of Emesis (PUQE) score 48 hours after starting treatment.
      Secondary outcome measures were duration of treatment, improvement in symptom
      scores and ketonuria at 48 hours, reattendances within 7 days of discharge and
      comparison of symptoms at 7 days postdischarge. RESULTS: 152/174 eligible women
      agreed to participate with 77/152 (51%) recruited to the RCT and 75/152 (49%) to
      the PPT.Patients were initially compared in four groups (randomised IP,
      randomised OP, non-randomised IP and non-randomised OP). Comprehensive cohort
      analysis of participants in the randomised group (RCT) and non-randomised group
      (PPT) did not demonstrate any differences in patient demographics or baseline
      clinical characteristics. Pooled analysis of IP versus OP groups showed no
      difference in reduction in PUQE score at 48 hours (p=0.86). There was no
      difference in change in eating score (p=0.69), drinking score (p=0.77), well
      being rating (p=0.64) or reduction in ketonuria (p=0.47) at 48 hours, with no
      difference in duration of index treatment episode (p=0.83) or reattendances
      within 7 days (p=0.52). CONCLUSIONS: Ambulatory management is an effective direct
      alternative to IP management of severe NVP. The trial also demonstrated that many
      women requiring treatment for severe NVP have strong preferences regarding
      treatment setting, which may need to be considered by care providers, especially
      given the psychological impact of severe NVP. TRIAL REGISTRATION NUMBER:
      http://www.isrctn.com/ISRCTN24659467 (March 2014).

PMID- 29222134
TI  - Workplace violence, psychological stress, sleep quality and subjective health in
      Chinese doctors: a large cross-sectional study.
AB  - BACKGROUND: Workplace violence (WPV) against healthcare workers is known as
      violence in healthcare settings and referring to the violent acts that are
      directed towards doctors, nurses or other healthcare staff at work or on duty.
      Moreover, WPV can cause a large number of adverse outcomes. However, there is not
      enough evidence to test the link between exposure to WPV against doctors,
      psychological stress, sleep quality and health status in China. OBJECTIVES: This
      study had three objectives: (1) to identify the incidence rate of WPV against
      doctors under a new classification, (2) to examine the association between
      exposure to WPV, psychological stress, sleep quality and subjective health of
      Chinese doctors and (3) to verify the partial mediating role of psychological
      stress. DESIGN: A cross-sectional online survey study. SETTING: The survey was
      conducted among 1740 doctors in tertiary hospitals, 733 in secondary hospital and
      139 in primary hospital across 30 provinces of China. PARTICIPANTS: A total of
      3016 participants were invited. Ultimately, 2617 doctors completed valid
      questionnaires. The effective response rate was 86.8%. RESULTS: The results
      demonstrated that the prevalence rate of exposure to verbal abuse was the highest
      (76.2%), made difficulties (58.3%), smear reputation (40.8%), mobbing behaviour
      (40.2%), intimidation behaviour (27.6%), physical violence (24.1%) and sexual
      harassment (7.8%). Exposure to WPV significantly affected the psychological
      stress, sleep quality and self-reported health of doctors. Moreover,
      psychological stress partially mediated the relationship between work-related
      violence and health damage. CONCLUSION: In China, most doctors have encountered
      various WPV from patients and their relatives. The prevalence of three new types
      of WPV have been investigated in our study, which have been rarely mentioned in
      past research. A safer work environment for Chinese healthcare workers needs to
      be provided to minimise health threats, which is a top priority for both
      government and society.

PMID- 29222136
TI  - Effects of a culturally tailored parenting support programme in Somali-born
      parents' mental health and sense of competence in parenting: a randomised
      controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of a culturally tailored parenting
      support programme on Somali-born parents' mental health and sense of competence
      in parenting. DESIGN: Randomised controlled trial. SETTING: A city in the middle
      of Sweden. PARTICIPANTS: Somali-born parents (n=120) with children aged 11-16
      years and self-perceived stress in their parenting were randomised to an
      intervention group (n=60) or a waiting-list control group (n=60). INTERVENTION:
      Parents in the intervention group received culturally tailored societal
      information combined with the Connect parenting programme during 12 weeks for 1-2
      hours per week. The intervention consisted of a standardised training programme
      delivered by nine group leaders of Somali background. OUTCOME: The General Health
      Questionnaire 12 was used to measure parents' mental health and the Parenting
      Sense of Competence scale to measure parent satisfaction and efficacy in the
      parent role. Analysis was conducted using intention-to-treat principles. RESULTS:
      The results indicated that parents in the intervention group showed significant
      improvement in mental health compared with the parents in the control group at a
      2-month follow-up: B=3.62, 95% CI 2.01 to 5.18, p<0.001. Further, significant
      improvement was found for efficacy (B=-6.72, 95% CI -8.15 to -5.28, p<0.001) and
      satisfaction (B=-4.48, 95% CI -6.27 to -2.69, p<0.001) for parents in the
      intervention group. Parents' satisfaction mediated the intervention effect on
      parental mental health (beta=-0.88, 95% CI -1.84 to -0.16, p=0.047). CONCLUSION:
      The culturally tailored parenting support programme led to improved mental health
      of Somali-born parents and their sense of competence in parenting 2 months after
      the intervention. The study underlines the importance of acknowledging immigrant
      parents' need for societal information in parent support programmes and the
      importance of delivering these programmes in a culturally sensitive manner.
      CLINICAL TRIAL REGISTRATION: NCT02114593.

PMID- 29222137
TI  - Benefits of probiotics in preterm neonates in low-income and medium-income
      countries: a systematic review of randomised controlled trials.
AB  - OBJECTIVE: Although there is an overall reduction in underfive mortality rate,
      the progress in reducing neonatal mortality rate has been very slow. Over the
      last 20 years, preterm births have steadily increased in low-income and medium
      income countries (LMICs) particularly in sub-Saharan Africa and South Asia.
      Preterm birth is associated with increased mortality and morbidity, particularly
      in LMICs. Based on systematic reviews of randomised controlled trials (RCTs),
      many neonatal units in high-income countries have adopted probiotics as standard
      of care for preterm neonates. We aimed to systematically review the safety and
      efficacy of probiotics in reducing mortality and morbidity in preterm neonates in
      LMICs. DESIGN: Systematic review and meta-analysis of RCTs. DATA SOURCES:
      Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index
      of Nursing and Allied Health Literature and E-abstracts from Pediatric Academic
      Society meetings and other paediatric and neonatal conference proceedings were
      searched in January 2017. ELIGIBILITY CRITERIA: RCTs comparing probiotics versus
      placebo/no probiotic in preterm neonates (gestation<37 weeks) conducted in LMICs.
      RESULTS: Total 23 (n=4783) RCTs from 4 continents and 10 LMICs were eligible for
      inclusion in the meta-analysis using fixed effect model. The risk of necrotising
      enterocolitis (NEC greater than or equal to stage II) (risk ratio (RR) 0.46 (95%
      CI 0.34 to 0.61), P<0.00001, numbers needed to treat (NNT) 25 (95% CI 20 to 50)),
      late-onset sepsis (LOS) (RR 0.80 (95% CI 0.71 to 0.91), P=0.0009, NNT 25 (95% CI
      17 to 100)) and all-cause mortality (RR 0.73 (95% CI 0.59 to 0.90), P=0.003, NNT
      50 (95% CI 25 to 100)) were significantly lower in probiotic supplemented
      neonates. The results were significant on random effects model analysis and after
      excluding studies with high risk of bias. No significant adverse effects were
      reported. CONCLUSION: Probiotics have significant potential to reduce mortality
      and morbidity (eg, NEC, LOS) in preterm neonates in LMICs.

PMID- 29222140
TI  - Correction to "TD-19, an Erlotinib Derivative, Induces Epidermal Growth Factor
      Receptor Wild-Type Nonsmall-Cell Lung Cancer Apoptosis through CIP2A-Mediated
      Pathway".

PMID- 29222139
TI  - Effect of Losartan on Right Ventricular Dysfunction: Results From the Double
      Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of
      Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With
      Repaired Tetralogy of Fallot.
AB  - BACKGROUND: The effect of angiotensin II receptor blockers on right ventricular
      (RV) function is still unknown. Angiotensin II receptor blockers are beneficial
      in patients with acquired left ventricular dysfunction, and recent findings have
      suggested a favorable effect in symptomatic patients with systemic RV
      dysfunction. The current study aimed to determine the effect of losartan, an
      angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after
      repaired tetralogy of Fallot. METHODS: The REDEFINE trial (Right Ventricular
      Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin
      Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1
      randomized, double-blind, placebo-controlled study. Adults with repaired
      tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but
      without severe valvular dysfunction were eligible. Patients were randomly
      assigned between losartan (150 mg daily) and placebo with target treatment
      duration between 18 and 24 months. The primary outcome was RV EF change,
      determined by cardiovascular MRI in intention-to-treat analysis. RESULTS: Of 95
      included patients, 47 patients received 150 mg losartan daily (age, 38.0+/-12.4
      years; 74% male), and 48 patients received placebo (age, 40.6+/-11.4 years; 63%
      male). Overall, RV EF did not change in patients allocated to losartan (n=42)
      (44.4+/-5.1% to 45.2+/-5.0%) and placebo (n=46) (43.2+/-6.3% to 43.6+/-6.9%).
      Losartan did not significantly improve RV EF in comparison with placebo (+0.51%;
      95% confidence interval, -1.0 to +2.0; P=0.50). No significant treatment effects
      were found on secondary outcomes: left ventricular EF, peak aerobic exercise
      capacity, and N-terminal pro-brain natriuretic peptide (P>0.30 for all). In
      predefined subgroup analyses, losartan did not have a statistically significant
      impact on RV EF in subgroups with symptoms, restrictive RV, RV EF<40%, pulmonary
      valve replacement, or QRS fragmentation. However, in a post hoc analysis,
      losartan was associated with improved RV EF in a subgroup (n=30) with
      nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous
      pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4;
      P=0.045). CONCLUSIONS: Losartan had no significant effect on RV dysfunction or
      secondary outcome parameters in repaired tetralogy of Fallot. Future larger
      studies may determine whether there might be a role for losartan in specific
      vulnerable subgroups. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

PMID- 29222141
TI  - Looking to tomorrow.

PMID- 29222138
TI  - Application of Large-Scale Aptamer-Based Proteomic Profiling to Planned
      Myocardial Infarctions.
AB  - BACKGROUND: Emerging proteomic technologies using novel affinity-based reagents
      allow for efficient multiplexing with high-sample throughput. To identify early
      biomarkers of myocardial injury, we recently applied an aptamer-based proteomic
      profiling platform that measures 1129 proteins to samples from patients
      undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model
      of planned myocardial injury. Here, we examined the scalability of this approach
      using a markedly expanded platform to study a far broader range of human proteins
      in the context of myocardial injury. METHODS: We applied a highly multiplexed,
      expanded proteomic technique that uses single-stranded DNA aptamers to assay 4783
      human proteins (4137 distinct human gene targets) to derivation and validation
      cohorts of planned myocardial injury, individuals with spontaneous myocardial
      infarction, and at-risk controls. RESULTS: We found 376 target proteins that
      significantly changed in the blood after planned myocardial injury in a
      derivation cohort (n=20; P<1.05E-05, 1-way repeated measures analysis of
      variance, Bonferroni threshold). Two hundred forty-seven of these proteins were
      validated in an independent planned myocardial injury cohort (n=15; P<1.33E-04, 1
      way repeated measures analysis of variance); >90% were directionally consistent
      and reached nominal significance in the validation cohort. Among the validated
      proteins that were increased within 1 hour after planned myocardial injury, 29
      were also elevated in patients with spontaneous myocardial infarction (n=63;
      P<6.17E-04). Many of the novel markers identified in our study are intracellular
      proteins not previously identified in the peripheral circulation or have
      functional roles relevant to myocardial injury. For example, the cardiac LIM
      protein, cysteine- and glycine-rich protein 3, is thought to mediate cardiac
      mechanotransduction and stress responses, whereas the mitochondrial ATP synthase
      F0 subunit component is a vasoactive peptide on its release from cells. Last, we
      performed aptamer-affinity enrichment coupled with mass spectrometry to
      technically verify aptamer specificity for a subset of the new biomarkers.
      CONCLUSIONS: Our results demonstrate the feasibility of large-scale aptamer
      multiplexing at a level that has not previously been reported and with sample
      throughput that greatly exceeds other existing proteomic methods. The expanded
      aptamer-based proteomic platform provides a unique opportunity for biomarker and
      pathway discovery after myocardial injury.

PMID- 29222142
TI  - Dramatic decline in donkey populations blamed on consumer demand for 'ejiao'.

PMID- 29222144
TI  - New chief vet for UK appointed by Defra.

PMID- 29222143
TI  - Consulting on bTB in Northern Ireland.

PMID- 29222145
TI  - What role does diet play in the decline of puffins?
AB  - Eleanor Taylor explains how bird lovers are helping conservation charity RSPB
      understand puffin populations.

PMID- 29222146
TI  - Medicines update.

PMID- 29222147
TI  - New cases of Alabama rot confirmed.

PMID- 29222148
TI  - Looking out for avian influenza in backyard and small poultry flocks.
AB  - This article has been prepared by David Welchman, veterinary lead of the Avian
      Expert Group, and Anna Brzozowska, surveillance data scientist, of the APHA's
      Surveillance Intelligence Unit.

PMID- 29222149
TI  - Compressive hydrated nucleus pulposus extrusion: is surgery necessary?

PMID- 29222151
TI  - Professional responsibility.

PMID- 29222152
TI  - Changes to ionising radiation regulations.

PMID- 29222153
TI  - The future of keeping pet reptiles and amphibians.

PMID- 29222154
TI  - Who owns the countryside?

PMID- 29222156
TI  - Brachycephalics and advertising.

PMID- 29222155
TI  - Brachycephalics and advertising.

PMID- 29222157
TI  - Awards to receive CPD support.

PMID- 29222158
TI  - Not man's best friend.
AB  - Gemma Bourne describes her dog, Max, who displays challenging behaviour and what
      she wants from her vet.

PMID- 29222159
TI  - My week.
AB  - Scarlett Beesley is a ward veterinary nurse at Lumbry Park Veterinary Specialists
      in Alton, Hampshire. Here, she describes a recent week.

PMID- 29222161
TI  - Detection of Proteome Diversity Resulted from Alternative Splicing is Limited by
      Trypsin Cleavage Specificity.
AB  - Alternative splicing dramatically increases transcriptome complexity but its
      contribution to proteome diversity remains controversial. Exon-exon junction
      spanning peptides provide direct evidence for the translation of specific splice
      isoforms and are critical for delineating protein isoform complexity. Here we
      found that junction-spanning peptides are underrepresented in publicly available
      mass spectrometry-based shotgun proteomics data sets. Further analysis showed
      that evolutionarily conserved preferential nucleotide usage at exon boundaries
      increases the occurrence of lysine- and arginine-coding triplets at the end of
      exons. Because both lysine and arginine residues are cleavage sites of trypsin,
      the nearly exclusive use of trypsin as the protein digestion enzyme in shotgun
      proteomic analyses hinders the detection of junction-spanning peptides. To study
      the impact of enzyme selection on splice junction detectability, we performed in
      silico digestion of the human proteome using six proteases. The six enzymes
      created a total of 161,125 detectable junctions, and only 1,029 were common
      across all enzyme digestions. Chymotrypsin digestion provided the largest number
      of detectable junctions. Our experimental results further showed that combination
      of a chymotrypsin-based human proteome analysis with a trypsin-based analysis
      increased detection of junction-spanning peptides by 37% over the trypsin-only
      analysis and identified over a thousand junctions that were undetectable in fully
      tryptic digests. Our study demonstrates that detection of proteome diversity
      resulted from alternative splicing is limited by trypsin cleavage specificity,
      and that complementary digestion schemes will be essential to comprehensively
      analyze the translation of alternative splicing isoforms.

PMID- 29222160
TI  - The interactome of intact mitochondria by cross-linking mass spectrometry
      provides evidence for coexisting respiratory supercomplexes.
AB  - Mitochondria exert an immense amount of cytophysiological functions, but the
      structural basis of most of these processes is still poorly understood. Here we
      use cross-linking mass spectrometry to probe the organization of proteins in
      native mouse heart mitochondria. Our approach provides the largest survey of
      mitochondrial protein interactions reported so far. In total, we identify 3,322
      unique residue-to-residue contacts involving half of the mitochondrial proteome
      detected by bottom-up proteomics. The obtained mitochondrial protein interactome
      gives insights in the architecture and submitochondrial localization of defined
      protein assemblies, and reveals the mitochondrial localization of four proteins
      not yet included in the MitoCarta database. As one of the highlights, we show
      that the oxidative phosphorylation complexes I-V exist in close spatial
      proximity, providing direct evidence for supercomplex assembly in intact
      mitochondria. The specificity of these contacts is demonstrated by comparative
      analysis of mitochondria after high salt treatment, which disrupts the native
      supercomplexes and substantially changes the mitochondrial interactome.

PMID- 29222162
TI  - Dual Inhibition of PIK3C3 and FGFR as a New Therapeutic Approach to Treat Bladder
      Cancer.
AB  - Purpose: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant
      anti-bladder cancer activity in vitro and in vivo via promoting autophagy
      dependent cell death. Here, we aim to elucidate the underlying
      mechanisms.Experimental Design: Autophagy flux, morphology, and intracellular
      organelles were evaluated by Western blotting, transmission electron microscope,
      and fluorescence microscope. Molecular docking and surface plasmon resonance
      assay were performed to identify drug-protein interaction. Lentiviral delivery of
      cDNA or shRNA and CRISPR/Cas9-mediated genome editing was used to modulate gene
      expression. Mitochondrial oxygen consumption rate was measured by a Seahorse
      XFe24 extracellular flux analyzer, and ROS level was measured by flow
      cytometry.Results: MPT0L145 persistently increased incomplete autophagy and phase
      lucent vacuoles at the perinuclear region, which were identified as enlarged and
      alkalinized late-endosomes. Screening of a panel of lipid kinases revealed that
      MPT0L145 strongly inhibits PIK3C3 with a Kd value of 0.53 nmol/L. Ectopic
      expression of PIK3C3 reversed MPT0L145-increased cell death and incomplete
      autophagy. Four residues (Y670, F684, I760, D761) at the ATP-binding site of
      PIK3C3 are important for the binding of MPT0L145. In addition, MPT0L145 promotes
      mitochondrial dysfunction, ROS production, and DNA damage, which may in part,
      contribute to cell death. ATG5-knockout rescued MPT0L145-induced cell death,
      suggesting simultaneous induction of autophagy is crucial to its anticancer
      activity. Finally, our data demonstrated that MPT0L145 is able to overcome
      cisplatin resistance in bladder cancer cells.Conclusions: MPT0L145 is a first-in
      class PIK3C3/FGFR inhibitor, providing an innovative strategy to design new
      compounds that increase autophagy, but simultaneously perturb its process to
      promote bladder cancer cell death. Clin Cancer Res; 24(5); 1176-89. (c)2017 AACR.

PMID- 29222163
TI  - Novel In Vitro Cancer Models for Optimizing Anti-EGFR Therapies.
AB  - Preclinical models, which are able to recapitulate the biology and pathology of
      the original individual cancer, are needed to better investigate mechanisms of
      response and resistance to anticancer therapies. In this respect, novel in vitro
      models for metastatic colorectal cancer could be of high value. Clin Cancer Res;
      24(4); 727-9. (c)2017 AACRSee related article by Luraghi et al., p. 807.

PMID- 29222164
TI  - Cardiac Resynchronization Therapy in Heart Failure: Do Evidence-Based Guidelines
      Follow the Evidence?

PMID- 29222165
TI  - Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by alpha
      Hemolysin.
AB  - Numerous studies have reported sex bias in infectious diseases, with bias
      direction dependent on pathogen and site of infection. Staphylococcus aureus is
      the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in
      susceptibility to S. aureus SSTI has not been described. A search of electronic
      health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus
      females. To investigate the physiological basis of this bias, we compared
      outcomes between male and female mice in a model of S. aureus dermonecrosis.
      Consistent with the epidemiological data, female mice were better protected
      against SSTI, with reduced dermonecrosis followed later by increased bacterial
      clearance. Protection in females was disrupted by ovariectomy and restored by
      short-term estrogen administration. Importantly, this sex bias was mediated by a
      sex-specific response to the S. aureus-secreted virulence factor alpha-hemolysin
      (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine
      production in the skin of female, but not male, mice when compared with infection
      with an isogenic hla deletion mutant. This differential response was conserved
      following injection with Hla alone, demonstrating a direct response to Hla
      independent of bacterial burden. Additionally, neutrophils, essential for
      clearing S. aureus, demonstrated sex-specific S. aureus bactericidal capacity ex
      vivo. This work suggests that sex-specific skin innate responsiveness to Hla and
      neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI
      in females. Understanding the molecular mechanisms controlling this sex bias may
      reveal novel targets to promote host innate defense against S. aureus skin
      infection.

PMID- 29222166
TI  - Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in
      HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.
AB  - IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell
      counts after virologically successful antiretroviral therapy. IL-7 increases
      total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific
      CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor
      required for 4-1BB-mediated costimulation, is lost from chronically stimulated
      virus-specific CD8 T cells with progression of HIV infection in humans and during
      chronic lymphocytic choriomeningitis infection in mice. Previous results showed
      that IL-7 can restore TRAF1 expression in virus-specific CD8 T cells in mice,
      rendering them sensitive to anti-4-1BB agonist therapy. In this article, we show
      that IL-7 therapy in humans increases the number of circulating HIV-specific CD8
      T cells. For a subset of patients, we also observed an increased frequency of
      TRAF1+ HIV-specific CD8 T cells 10 wk after completion of IL-7 treatment. IL-7
      treatment increased levels of phospho-ribosomal protein S6 in HIV-specific CD8 T
      cells, suggesting increased activation of the metabolic checkpoint kinase mTORC1.
      Thus, IL-7 therapy in antiretroviral therapy-treated patients induces sustained
      changes in the number and phenotype of HIV-specific T cells.

PMID- 29222168
TI  - Altered Marginal Zone B Cell Selection in the Absence of IkappaBNS.
AB  - Marginal zone (MZ) B cells reside in the splenic MZ and play important roles in T
      cell-independent humoral immune responses against blood-borne pathogens.
      IkappaBNS-deficient bumble mice exhibit a severe reduction in the MZ B
      compartment but regain an MZ B population with age and, thus, represent a
      valuable model to examine the biology of MZ B cells. In this article, we
      characterized the MZ B cell defect in further detail and investigated the nature
      of the B cells that appear in the MZ of aged bumble mice. Flow cytometry analysis
      of the splenic transitional B cell subsets demonstrated that MZ B cell
      development was blocked at the transitional-1 to transitional-2-MZ precursor
      stage in the absence of functional IkappaBNS. Immunohistochemical analysis of
      spleen sections from wild-type and bumble mice revealed no alteration in the
      cellular MZ microenvironment, and analysis of bone marrow chimeras indicated that
      the MZ B cell development defect in bumble mice was B cell intrinsic. Further, we
      demonstrate that the B cells that repopulate the MZ in aged bumble mice were
      distinct from age-matched wild-type MZ B cells. Specifically, the expression of
      surface markers characteristic for MZ B cells was altered and the L chain
      Iglambda+ repertoire was reduced in bumble mice. Finally, plasma cell
      differentiation of sorted LPS-stimulated MZ B cells was impaired, and aged bumble
      mice were unable to respond to NP-Ficoll immunization. These results demonstrate
      that IkappaBNS is required for an intact MZ B cell compartment in C57BL/6 mice.

PMID- 29222167
TI  - Cytoplasmic Linker Protein CLIP170 Negatively Regulates TLR4 Signaling by
      Targeting the TLR Adaptor Protein TIRAP.
AB  - Cytoplasmic linker protein 170 (CLIP170) is a CAP-Gly domain-containing protein
      that is associated with the plus end of growing microtubules and implicated in
      various cellular processes, including the regulation of microtubule dynamics,
      cell migration, and intracellular transport. Our studies revealed a previously
      unrecognized property and role of CLIP170. We identified CLIP170 as one of the
      interacting partners of Brucella effector protein TcpB that negatively regulates
      TLR2 and TLR4 signaling. In this study, we demonstrate that CLIP170 interacts
      with the TLR2 and TLR4 adaptor protein TIRAP. Furthermore, our studies revealed
      that CLIP170 induces ubiquitination and subsequent degradation of TIRAP to
      negatively regulate TLR4-mediated proinflammatory responses. Overexpression of
      CLIP170 in mouse macrophages suppressed the LPS-induced expression of IL-6 and
      TNF-alpha whereas silencing of endogenous CLIP170 potentiated the levels of
      proinflammatory cytokines. In vivo silencing of CLIP170 in C57BL/6 mice by
      CLIP170-specific small interfering RNA enhanced LPS-induced IL-6 and TNF-alpha
      expression. Furthermore, we found that LPS modulates the expression of CLIP170 in
      mouse macrophages. Overall, our experimental data suggest that CLIP170 serves as
      an intrinsic negative regulator of TLR4 signaling that targets TIRAP.

PMID- 29222169
TI  - Nanoscale Tuning of VCAM-1 Determines VLA-4-Dependent Melanoma Cell Plasticity on
      RGD Motifs.
AB  - The biophysical fine-tuning of cancer cell plasticity is crucial for tumor
      progression but remains largely enigmatic. Although vascular cell adhesion
      molecule-1 (VCAM-1/CD106) has been implicated in melanoma progression, here its
      presentation on endothelial cells was associated with diminished melanoma cell
      spreading. Using a specific nanoscale modulation of VCAM-1 (tunable from 70 to
      670 ligands/MUm2) next to integrin ligands (RGD motifs) in a bifunctional system,
      reciprocal regulation of integrin alpha4 (ITGA4/VLA-4/CD49d)-dependent adhesion
      and spreading of melanoma cells was found. As the VCAM-1/VLA-4 receptor pair
      facilitated adhesion, while at the same time antagonizing RGD-mediated spreading,
      melanoma cell morphogenesis on these bifunctional matrices was directly regulated
      by VCAM-1 in a dichotomic and density-dependent fashion. This was accompanied by
      concordant regulation of F-actin cytoskeleton remodeling, Rac1-expression, and
      paxillin-related adhesion formation. The novel function of VCAM-1 was
      corroborated in vivo using two murine models of pulmonary metastasis. The
      regulation of melanoma cell plasticity by VCAM-1 highlights the complex
      regulation of tumor-matrix interactions.Implications: Nanotechnology has revealed
      a novel dichotomic function of the VCAM-1/VLA-4 interaction on melanoma cell
      plasticity, as nanoscale tuning of this interaction reciprocally determines
      adhesion and spreading in a ligand density-dependent manner. Mol Cancer Res;
      16(3); 528-42. (c)2017 AACR.

PMID- 29222171
TI  - TANKYRASE Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR
      Inhibition, Mutually Affecting beta-CATENIN and AKT Signaling in Colorectal
      Cancer.
AB  - Overactivation of the WNT/beta-CATENIN signaling axis is a common denominator in
      colorectal cancer. Currently, there is no available WNT inhibitor in clinical
      practice. Although TANKYRASE (TNKS) inhibitors have been proposed as promising
      candidates, there are many colorectal cancer models that do not respond
      positively to TNKS inhibition in vitro and in vivo Therefore, a combinatorial
      therapeutic approach combining a TNKS inhibitor (G007-LK) with PI3K (BKM120) and
      EGFR (erlotinib) inhibitors in colorectal cancer was investigated. The data
      demonstrate that TNKS inhibition enhances the effect of PI3K and EGFR inhibition
      in the TNKS inhibitor-sensitive COLO320DM, and in the nonsensitive HCT-15 cell
      line. In both cell lines, combined TNKS/PI3K/EGFR inhibition is more effective at
      reducing growth than a dual TNKS/MEK inhibition. TNKS/PI3K/EGFR inhibition
      affected in a context-dependent manner components of the WNT/beta-CATENIN,
      AKT/mTOR, EGFR, and RAS signaling pathways. TNKS/PI3K/EGFR inhibition also
      efficiently reduced growth of both COLO320DM and HCT-15 tumor xenografts in vivo
      At the highest doses, tumor xenograft growth was halted without affecting the
      body weight of the tested animals.Implications: Combining TNKS inhibitors with
      PI3K and EGFR inhibition may expand the therapeutic arsenal against colorectal
      cancers. Mol Cancer Res; 16(3); 543-53. (c)2017 AACR.

PMID- 29222170
TI  - Imprecision and DNA Break Repair Biased towards Incompatible End Joining in
      Leukemia.
AB  - Cancer is a genetic disease caused by mutations and chromosomal abnormalities
      that contribute to uncontrolled cell growth. In addition, cancer cells can
      rapidly respond to conventional and targeted therapies by accumulating novel and
      often specific genetic lesions leading to acquired drug resistance and relapsing
      disease. In chronic lymphocytic leukemia (CLL), however, diverse chromosomal
      aberrations often occur. In many cases, improper repair of DNA double-strand
      breaks (DSB) is a major source for genomic abnormalities. Therefore, this study
      examined the repair of DNA DSBs by nonhomologous end joining (NHEJ) in CLL by
      performing plasmid-based repair assays in primary CLL cells and normal B cells,
      isolated from patients, as well as TALEN/Cas9-induced chromosomal deletions in
      the CLL cell line Mec1. It is demonstrated that DNA repair is aberrant in CLL
      cells, featuring perturbed DNA break structure preference with efficient joining
      of noncohesive ends and more deletions at repair junctions. In addition,
      increased microhomology-mediated end joining (MMEJ) of DNA substrates was
      observed in CLL together with increased expression of MMEJ-specific repair
      factors. In summary, these data identify major differences in DNA repair
      efficiency between CLL cells and normal B cells isolated from
      patients.Implications: This study suggests inherently aberrant DNA DSB repair in
      the acquisition of subclonal genomic structural variations important for clonal
      evolution and treatment resistance in CLL. Mol Cancer Res; 16(3); 428-38. (c)2017
      AACR.

PMID- 29222173
TI  - The bright spark who lit up Glasgow.

PMID- 29222172
TI  - Proximal Aberrant Crypt Foci Associate with Synchronous Neoplasia and Are Primed
      for Neoplastic Progression.
AB  - Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion
      found within the human colon. Despite their relatively high frequency in the
      distal colon, few studies have examined the molecular characteristics of ACF
      within the proximal colon. In the following study, clinical participants (n =
      184) were screened for ACF using high-definition chromoendoscopy with contrast
      dye-spray. Following pathologic confirmation, ACF biopsies were subjected to
      laser capture microdissection (LCM), and epithelial cells were evaluated for
      somatic mutations with a customized colorectal cancer mutation panel using DNA
      mass spectrometry. Samples were further characterized for microsatellite
      instability (MSI). Logistic models were used to associate proximal ACF with
      synchronous (detected during the same procedure) neoplasia. Thirty-nine percent
      of participants had at least one histologically confirmed proximal ACF.
      Individuals with a proximal ACF were significantly more likely to present with a
      synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or
      tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12
      6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared
      with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS,
      and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often
      MSI-high, but there were no differences in MSI status observed by colonic
      location. In summary, ACF are identified in the proximal colons of approximately
      40% of individuals undergoing chromoendoscopy and more often in patients with
      synchronous proximal adenomas.Implications: This study provides the most complete
      set of data, to date, that ACF represent the earliest step in the adenoma
      carcinoma sequence but remain below the detection limit of conventional
      endoscopy.Visual Overview:
      http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer
      Res; 16(3); 486-95. (c)2017 AACR.

PMID- 29222174
TI  - Phosphatase PP2A and microtubule-mediated pulling forces disassemble centrosomes
      during mitotic exit.
AB  - Centrosomes are microtubule-nucleating organelles that facilitate chromosome
      segregation and cell division in metazoans. Centrosomes comprise centrioles that
      organize a micron-scale mass of protein called pericentriolar material (PCM) from
      which microtubules nucleate. During each cell cycle, PCM accumulates around
      centrioles through phosphorylation-mediated assembly of PCM scaffold proteins.
      During mitotic exit, PCM swiftly disassembles by an unknown mechanism. Here, we
      used Caenorhabditis elegans embryos to determine the mechanism and importance of
      PCM disassembly in dividing cells. We found that the phosphatase PP2A and its
      regulatory subunit SUR-6 (PP2ASUR-6), together with cortically directed
      microtubule pulling forces, actively disassemble PCM. In embryos depleted of
      these activities, ~25% of PCM persisted from one cell cycle into the next.
      Purified PP2ASUR-6 could dephosphorylate the major PCM scaffold protein SPD-5 in
      vitro Our data suggest that PCM disassembly occurs through a combination of
      dephosphorylation of PCM components and force-driven fragmentation of the PCM
      scaffold.

PMID- 29222177
TI  - Muscular dystrophy: Are we looking for subtle signs?

PMID- 29222178
TI  - Bilateral palatine ulcers in a neonate: Bednar's aphthae.

PMID- 29222175
TI  - Chitin protects the gut epithelial barrier in a protochordate model of DSS
      induced colitis.
AB  - The gastrointestinal tract of Ciona intestinalis, a solitary tunicate that siphon
      filters water, shares similarities with its mammalian counterpart. The Ciona gut
      exhibits other features that are unique to protochordates, including certain
      immune molecules, and other characteristics, e.g. chitin-rich mucus, which
      appears to be more widespread than considered previously. Exposure of Ciona to
      dextran sulphate sodium (DSS) induces a colitis-like phenotype similar to that
      seen in other systems, and is characterized by alteration of epithelial
      morphology and infiltration of blood cells into lamina propria-like regions. DSS
      treatment also influences the production and localization of a secreted immune
      molecule shown previously to co-localize to chitin-rich mucus in the gut.
      Resistance to DSS is enhanced by exposure to exogenous chitin microparticles,
      suggesting that endogenous chitin is critical to barrier integrity.
      Protochordates, such as Ciona, retain basic characteristics found in other more
      advanced chordates and can inform us of uniquely conserved signals shaping host
      microbiota interactions in the absence of adaptive immunity. These simpler model
      systems may also reveal factors and processes that modulate recovery from
      colitis, the role gut microbiota play in the onset of the disease, and the rules
      that help govern the reestablishment and maintenance of gut homeostasis.

PMID- 29222176
TI  - Ca2+ releases E-Syt1 autoinhibition to couple ER-plasma membrane tethering with
      lipid transport.
AB  - The extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins that
      bind the plasma membrane (PM) via C2 domains and transport lipids between them
      via SMP domains. E-Syt1 tethers and transports lipids in a Ca2+-dependent manner,
      but the role of Ca2+ in this regulation is unclear. Of the five C2 domains of E
      Syt1, only C2A and C2C contain Ca2+-binding sites. Using liposome-based assays,
      we show that Ca2+ binding to C2C promotes E-Syt1-mediated membrane tethering by
      releasing an inhibition that prevents C2E from interacting with PI(4,5)P2-rich
      membranes, as previously suggested by studies in semi-permeabilized cells.
      Importantly, Ca2+ binding to C2A enables lipid transport by releasing a charge
      based autoinhibitory interaction between this domain and the SMP domain.
      Supporting these results, E-Syt1 constructs defective in Ca2+ binding in either
      C2A or C2C failed to rescue two defects in PM lipid homeostasis observed in E
      Syts KO cells, delayed diacylglycerol clearance from the PM and impaired Ca2+
      triggered phosphatidylserine scrambling. Thus, a main effect of Ca2+ on E-Syt1 is
      to reverse an autoinhibited state and to couple membrane tethering with lipid
      transport.

PMID- 29222179
TI  - HPV vaccination rate in French adolescent girls: an example of vaccine distrust.
AB  - OBJECTIVES: To explore the clinical issues of human papillomavirus (HPV)
      vaccination to develop explanatory hypotheses for the low level of vaccination
      among adolescent girls in France where the full course coverage is low (<15%).
      DESIGN: We used semistructured interviews. Our qualitative and phenomenological
      procedure applied interpretative phenomenological analysis. PARTICIPANTS: 16
      physicians regularly faced with the prescription of HPV vaccine, represented
      several medical specialties (paediatrics, general practice, internal medicine,
      gynaecology), with hospitalist or private practices. MAIN OUTCOME MEASURES: The
      results connect three superordinate themes grouping three concentric levels:
      within society, during the consultation and in the individual doctor's feelings.
      RESULTS: The modalities and contents of the information about HPV vaccination
      raise questions about the limitations of the information doctors receive. The
      ineluctable association between sexuality and HPV vaccination explains their
      reluctance to raise topics considered to be private. The reasons for HPV
      vaccination illustrate the difficulty of arguing in favour of it. In view of the
      frequent parental reluctance, which weakens the parent-physician alliance,
      physicians must take responsibility for defending the benefits of vaccination.
      They nonetheless remain citizens whose opinions may implicitly echo the general
      reluctance, promoted by disinformation. In delaying or avoiding the subject of
      vaccination, they involuntarily become an instrument of anti-vaccination
      discourse. CONCLUSIONS: It is imperative to improve the distribution of credible
      information about vaccination, unbiased and scientifically supported by a strong
      institutional position and to rethink the place of the clinician in the system of
      adolescent health and disease prevention in France.

PMID- 29222180
TI  - Big Science for patient centred care.

PMID- 29222181
TI  - Fifteen-minute consultation: an approach to a child presenting to the emergency
      department with acute psychotic symptoms.
AB  - Presentation of a child in the A&E with altered behaviour including psychotic
      features is not unusual. New-onset psychotic symptoms in children pose a
      significant diagnostic challenge due to several reasons. First, primary psychotic
      conditions are uncommon in pre-pubertal children. Second, differentiating between
      delirium and psychosis can be difficult in children, more so in infants, toddlers
      and young children. Third, intervening and managing a secondary cause of
      psychosis can significantly optimise outcome. Prompt recognition of a possible
      underlying cause for a child's psychotic behaviour is essential, and at the same
      time challenging, in the emergency department. This article attempts to present a
      systematic approach to a child with acute onset of psychotic symptoms in an
      emergency setting.

PMID- 29222182
TI  - Fifteen minute consultation: an approach to the child with chronic headaches.
AB  - Children with chronic headache are a common referral to paediatric outpatients.
      This article suggests an approach to the assessment and management of chronic
      headaches, offering practical strategies for management as there is limited
      literature in paediatrics for this.

PMID- 29222183
TI  - Default neglect in attempts at social influence.
AB  - Current theories suggest that people understand how to exploit common biases to
      influence others. However, these predictions have received little empirical
      attention. We consider a widely studied bias with special policy relevance: the
      default effect, which is the tendency to choose whichever option is the status
      quo. We asked participants (including managers, law/business/medical students,
      and US adults) to nudge others toward selecting a target option by choosing
      whether to present that target option as the default. In contrast to theoretical
      predictions, we find that people often fail to understand and/or use defaults to
      influence others, i.e., they show "default neglect." First, in one-shot default
      setting games, we find that only 50.8% of participants set the target option as
      the default across 11 samples (n = 2,844), consistent with people not
      systematically using defaults at all. Second, when participants have multiple
      opportunities for experience and feedback, they still do not systematically use
      defaults. Third, we investigate beliefs related to the default effect. People
      seem to anticipate some mechanisms that drive default effects, yet most people do
      not believe in the default effect on average, even in cases where they do use
      defaults. We discuss implications of default neglect for decision making, social
      influence, and evidence-based policy.

PMID- 29222184
TI  - Phosphorylation of the synaptonemal complex protein SYP-1 promotes meiotic
      chromosome segregation.
AB  - Chromosomes that have undergone crossing over in meiotic prophase must maintain
      sister chromatid cohesion somewhere along their length between the first and
      second meiotic divisions. Although many eukaryotes use the centromere as a site
      to maintain cohesion, the holocentric organism Caenorhabditis elegans instead
      creates two chromosome domains of unequal length termed the short arm and long
      arm, which become the first and second site of cohesion loss at meiosis I and II.
      The mechanisms that confer distinct functions to the short and long arm domains
      remain poorly understood. Here, we show that phosphorylation of the synaptonemal
      complex protein SYP-1 is required to create these domains. Once crossover sites
      are designated, phosphorylated SYP-1 and PLK-2 become cooperatively confined to
      short arms and guide phosphorylated histone H3 and the chromosomal passenger
      complex to the site of meiosis I cohesion loss. Our results show that PLK-2 and
      phosphorylated SYP-1 ensure creation of the short arm subdomain, promoting
      disjunction of chromosomes in meiosis I.

PMID- 29222185
TI  - p37/UBXN2B regulates spindle orientation by limiting cortical NuMA recruitment
      via PP1/Repo-Man.
AB  - Spindle orientation determines the axis of division and is crucial for cell fate,
      tissue morphogenesis, and the development of an organism. In animal cells,
      spindle orientation is regulated by the conserved Galphai-LGN-NuMA complex, which
      targets the force generator dynein-dynactin to the cortex. In this study, we show
      that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation
      in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical
      NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it
      acts independently of Galphai, the kinase Aurora A, and the phosphatase PP2A. Our
      data show that in anaphase, when the spindle elongates, PP1/Repo-Man promotes the
      accumulation of NuMA at the cortex. In metaphase, p37 negatively regulates this
      function of PP1, resulting in lower cortical NuMA levels and correct spindle
      orientation.

PMID- 29222186
TI  - New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport
      peroxisomes.
AB  - Microtubule-dependent long-distance movement of peroxisomes occurs in mammalian
      cells. However, its molecular mechanisms remain undefined. In this study, we
      identified three distinct splicing variants of human mitochondrial Rho GTPase-1
      (Miro1), each containing amino acid sequence insertions 1 (named Miro1-var2), 2
      (Miro1-var3), and both 1 and 2 (Miro1-var4), respectively, at upstream of the
      transmembrane domain. Miro1-var4 and Miro1-var2 are localized to peroxisomes in a
      manner dependent on the insertion 1 that is recognized by the cytosolic receptor
      Pex19p. Exogenous expression of Miro1-var4 induces accumulation of peroxisomes at
      the cell periphery and augments long-range movement of peroxisomes along
      microtubules. Depletion of all Miro1 variants by knocking down MIRO1 suppresses
      the long-distance movement of peroxisomes. Such abrogated movement is restored by
      reexpression of peroxisomal Miro1 variants. Collectively, our findings identify
      for the first time peroxisome-localized Miro1 variants as adapter proteins that
      link peroxisomes to the microtubule-dependent transport complexes including TRAK2
      in the intracellular translocation of peroxisomes in mammalian cells.

PMID- 29222193
TI  - A cholesterol-sensing mechanism unfolds.
AB  - Squalene monooxygenase (SM), which synthesizes a cholesterol precursor, is
      degraded when cholesterol levels in the endoplasmic reticulum (ER) membrane are
      high, but the signal for degradation was not known. In this issue of JBC, Brown
      and co-workers identify an N-terminal domain in SM that interconverts in a
      cholesterol-sensitive manner between a membrane-binding amphipathic helix and a
      soluble degradation-prone segment, providing the first example of a cholesterol
      degron collaboration.

PMID- 29222192
TI  - SUPPRESSOR OF GAMMA RESPONSE1 Links DNA Damage Response to Organ Regeneration.
AB  - In Arabidopsis, DNA damage-induced programmed cell death is limited to the
      meristematic stem cell niche and its early descendants. The significance of this
      cell-type-specific programmed cell death is unclear. Here, we demonstrate in
      roots that it is the programmed destruction of the mitotically compromised stem
      cell niche that triggers its regeneration, enabling growth recovery. In contrast
      to wild-type plants, sog1 plants, which are defective in damage-induced
      programmed cell death, maintain the cell identities and stereotypical structure
      of the stem cell niche after irradiation, but these cells fail to undergo cell
      division, terminating root growth. We propose DNA damage-induced programmed cell
      death is employed by plants as a developmental response, contrasting with its
      role as an anticarcinogenic response in animals. This role in plants may have
      evolved to restore the growth of embryos after the accumulation of DNA damage in
      seeds.

PMID- 29222194
TI  - Co-conspirators in a new mechanism for the degradation of Delta9-desaturase.
AB  - Delta9-Desaturases are central enzymes in unsaturated fatty acid synthesis
      regulated at the transcriptional and mRNA levels and by proteasomal degradation.
      A new study by Murakami et al. uncovers a novel regulatory pathway in which an N
      terminal di-proline motif in the Drosophila Delta9-desaturase mediates protein
      degradation by a calcium-dependent cysteine protease in response to unsaturated
      fatty acids. This study provides new details of desaturase regulation with
      therapeutic implications for the treatment of metabolic syndrome.

PMID- 29222195
TI  - Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative
      initiation of translation.

PMID- 29222196
TI  - Failure of prion protein oxidative folding guides the formation of toxic
      transmembrane forms.

PMID- 29222197
TI  - Are pulmonary fibrosis and Alzheimer's disease linked? Shared dysregulation of
      two miRNA species and downstream pathways accompany both disorders.

PMID- 29222198
TI  - Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients
      with Advanced Cancer.
AB  - BACKGROUND: Identifying predictors of treatment toxicity and overall survival
      (OS) is important for selecting patients who will benefit from chemotherapy. In
      younger patients with cancer, muscle mass and radiodensity are associated with
      treatment toxicity and OS. In this study, we investigated whether muscle mass,
      radiodensity, and strength were associated with treatment toxicity and OS in
      patients with advanced cancer aged 60 years or older. MATERIALS AND METHODS:
      Before starting palliative chemotherapy, muscle mass and radiodensity were
      assessed using computed tomography scans and muscle strength was assessed using a
      hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity
      resulting in dose reduction and/or discontinuation of treatment. Multiple
      logistic and Cox regression analyses were performed to study potential
      associations of muscle mass, radiodensity, and strength with treatment toxicity
      and OS, respectively. RESULTS: The participants were 103 patients, with a mean
      age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle
      parameters were not significantly associated with treatment toxicity. Higher
      muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence
      interval 1.00-1.05). Muscle mass and radiodensity were not significantly
      associated with OS. CONCLUSION: Higher muscle strength at the start of palliative
      chemotherapy is associated with significantly better OS in older patients with
      advanced cancer. None of the investigated muscle parameters were related to
      treatment toxicity. Future studies are needed to evaluate whether muscle strength
      can be used for treatment decisions in older patients with advanced cancer.
      IMPLICATIONS FOR PRACTICE: This study in older patients with advanced cancer
      showed that adequate muscle strength is associated with longer overall survival.
      The results of this study imply that muscle strength might be helpful in
      estimating survival and therefore in identifying older patients who will benefit
      from anticancer treatment.

PMID- 29222200
TI  - "Everyone thinks it's someone else's responsibility": training for sexual health
      doctors.

PMID- 29222199
TI  - Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with
      Brentuximab Vedotin: Identification and Report of Seven Cases.
AB  - BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or
      metastatic sex cord stromal tumors is rarely effective and is often accompanied
      by high adverse event rates. Expression of CD30 has been observed in testicular
      cancers, and patients with CD30-expressing embryonal carcinomas have worse
      progression-free survival and overall survival than those with CD30-negative
      tumors. The objective of this study (NCT01461538) was to characterize the
      antitumor activity of brentuximab vedotin in patients with CD30-expressing
      nonlymphomatous malignancies. Enrolled patients included seven patients with
      relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors
      described in this case series. MATERIALS AND METHODS: Forty patients with
      relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or
      testicular tumors were screened for CD30 expression; 14 patients had tumors that
      expressed CD30. Seven patients with CD30-expressing testicular cancer were
      enrolled in the treatment study: five patients with germ cell tumors, one patient
      with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients
      were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every
      3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles
      thereafter while the patient was receiving treatment. RESULTS: Two of seven
      patients achieved an objective response, including one durable complete response
      and one partial response at a single time point. Both responding patients had
      germ cell tumors. Treatment with brentuximab vedotin was generally well
      tolerated. CONCLUSION: Treatment of relapsed or refractory germ cell tumors with
      brentuximab vedotin can induce durable responses with a manageable toxicity
      profile. IMPLICATIONS FOR PRACTICE: This case series of seven patients with
      relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord
      stromal tumors demonstrates that brentuximab vedotin has activity against GCTs
      and is well tolerated in heavily pretreated patients with these aggressive tumor
      types. One patient achieved a complete response that has been durable for almost
      4 years since the discontinuation of treatment with brentuximab vedotin.
      Therefore, brentuximab vedotin may be a valuable option for physicians who care
      for this difficult-to-treat patient population.

PMID- 29222201
TI  - Self-regulated use of a wearable activity sensor is not associated with
      improvements in physical activity, cardiometabolic risk or subjective health
      status.

PMID- 29222203
TI  - Type and frequency of side effects during PC6 acupuncture: observations from
      therapists and patients participating in clinical efficacy trials of acupuncture.
AB  - BACKGROUND: Many therapists practise PC6 acupuncture for emesis (nausea and
      vomiting) during pregnancy, different cancer therapies, palliative care, after
      surgery, or to induce relaxing effects in general. Knowledge of side effects is
      central to shared decision-making. AIM: To describe the type and frequency of
      side effects and the level of needle-induced pain during PC6 acupuncture.
      METHODS: We included 1298 PC6 acupuncture treatments, delivered to 221
      participants (77% women, mean age 52.5, range 18-91 years). The subjects had
      received genuine PC6 acupuncture, in one of two previous randomised controlled
      trials, aimed at inducing antiemetic (n=100, with 100 providing data on side
      effects and 94 on needle-induced pain, respectively) or relaxing (n=121, with 120
      providing data) effects. Side effects during and after the acupuncture treatments
      were registered in structured treatment protocols and study diaries. RESULTS: No
      serious complications occurred. Side effects during the acupuncture sessions
      included minor bleeding in 5.0%, tiredness in 4.9%, numbness in 4.5% and
      dizziness in 1.4% of the 1298 treatments. After treatment, the mean proportions
      of participants reporting side effects each week were: tiredness 25.8%; feeling
      cold 17.8%; dizziness 9.7%; sweating 9.3%; haematoma 8.8%; and soreness at the
      needling sites 4.3%. Participants perceived the needling to be not painful (47.4%
      of participants), or mildly (39.1%), moderately (11.6%) or very painful (1.4%).
      CONCLUSIONS: Few side effects occurred and those that did were mild. Nearly 90%
      found PC6 acupuncture to be not painful or only mildly painful. Healthcare
      professionals may consider the observed levels of side effects when informing
      patients about side effects of PC6 acupuncture.

PMID- 29222205
TI  - Novel use of a trabecular metal spacer in the treatment of a long-standing ulnar
      fracture non-union.
AB  - The use of trabecular metal (TM) implants in spine and joint surgery is well
      documented. However, their use has yet to be reported as an alternative to either
      allograft or autograft in the management of fracture non-unions. We present our
      experience in using a TM implant for treating a patient with a long-standing
      ulnar fracture non-union. Excision of devitalised bone resulted in a 17 mm defect
      which the TM implant was used to infill. The defect was then bridged with a
      locking plate. At 2-year clinical and radiographic review, bony union and a pain
      free return to full function was noted. In this case, the use of a TM implant
      avoided the morbidity associated with an iliac crest autograft.

PMID- 29222206
TI  - Catastrophic catheter-induced coronary artery vasospasm successfully rescued
      using intravascular ultrasound imaging guidance.
AB  - A 46-year-old man underwent coronary angiography for stable angina. He developed
      inferior ST-segment myocardial infarction during the angiography. Intravascular
      ultrasound (IVUS) findings suggested coronary vasospasm. Intracoronary
      administration of isosorbide dinitrate restored the coronary flow. This case
      illustrates the essential role IVUS imaging played in establishing the diagnosis
      of catheter-induced coronary vasospasm.

PMID- 29222207
TI  - Perineal aggressive angiomyxoma in a menopausal woman.
AB  - Aggressive angiomyxoma (AA) is an uncommon mesenchymal tumour that is principally
      located in the soft tissues of the pelvis and perineum of young women. The
      primary features of this benign tumour are a local invasion, a high local
      recurrence rate and non-specific local clinical signs. We describe the case of a
      58-year-old woman, initially treated for a Bartholin's cyst. Histological
      examination indicated the presence of an AA. The MRI showed a 7 cm soft tissue
      mass extending from the lateral wall of the vagina, into the left buttock and
      down into the subcutaneous tissue. We performed a radical excision with wide
      resection, which is considered the standard gold treatment.

PMID- 29222208
TI  - Hypersomatotropism induced secondary polycythaemia leading to spontaneous
      pituitary apoplexy resulting in cure of acromegaly and remission of
      polycythaemia: 'The virtuous circle'.
AB  - A young man with subtle clinical features suggestive of hypersomatotropism
      presented with acute-onset severe headache. Relevant investigations confirmed
      polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with
      apoplexy. Secondary polycythaemia and myeloproliferative disorders were ruled
      out. At follow-up after 3 months, resolution of polycythaemia and acromegaly was
      observed, evident on normal haemoglobin levels, a normocellular marrow, and
      normal insulin-like growth factor-1 (IGF-1) with glucose-suppressed GH levels.
      Direct mitogenic properties of GH-IGF-1 axis on bone marrow progenitor cells may
      very rarely lead to erythroid hyperplasia and subsequent polycythaemia,
      reversible with successful therapy of acromegaly. In this case, polycythaemia
      secondary to hypersomatotropism likely resulted in pituitary apoplexy with
      subsequent remission of both acromegaly and resultant polycythaemia.

PMID- 29222209
TI  - Interhemispheric subdural and subarachnoid haemorrhage in a patient with
      amphetamine-induced vasculitis.

PMID- 29222210
TI  - Double duodenal perforation following foreign body ingestion.
AB  - Intentional ingestion of a foreign body in adults is a rare clinical
      presentation. This case is one of a 27-year-old Sudanese man who presented having
      swallowed a ballpoint pen intentionally. Clinical examination and plain chest
      radiograph exhibited no signs indicative of perforation with only a raised C
      reactive protein identified on blood tests. Subsequent gastroscopy revealed that
      the pen had simultaneously perforated the duodenum at both D1 and D3 requiring
      removal via a laparotomy. The patient fully recovered and was discharged 2 weeks
      postoperatively following psychiatric input.

PMID- 29222211
TI  - Lingual dyskinesia in hyperthyroidism.

PMID- 29222212
TI  - One long umbilical cord, four nuchal cord loops and a true knot.

PMID- 29222214
TI  - Treating patients with brain metastases has evolved: scalp-sparing, hippocampal
      avoidance whole brain radiotherapy with simultaneous integrated boost.

PMID- 29222213
TI  - Clinical examination and X-ray: an old approach to a current problem.

PMID- 29222215
TI  - Pulmonary embolism caused by thrombin-based haemostatic matrix.

PMID- 29222217
TI  - Necrotising pneumonia caused by non-PVL Staphylococcus aureus with 2-year follow
      up.
AB  - Necrotising pneumonia (NP) is a rare but life-threatening complication of
      pulmonary infection. It is characterised by progressive necrosis of lung
      parenchyma with cavitating foci evident upon radiological investigation. This
      article reports the case of a 52-year-old woman, immunocompetent healthcare
      professional presenting to Accident and Emergency with NP and Staphylococcus
      aureus septicaemia. The cavitating lesion was not identified on initial chest X
      ray leading to a delay in antimicrobial optimisation. However, the patient went
      on to achieve a full symptomatic recovery in 1 month and complete radiological
      recovery at 2-year follow-up. Long-term prognosis for adult cases of NP currently
      remains undocumented. This case serves as the first piece of published evidence
      documenting full physiological and radiological recovery following appropriate
      treatment of NP in an immunocompetent adult patient.

PMID- 29222216
TI  - Development of forced normalisation psychosis with ethosuximide.
AB  - A 50-year-old man with known multidrug resistant coexistent focal and generalised
      epilepsy was commenced on ethosuximide, with normalisation of his
      electroencephalogram and cessation of absence seizures. Within 3 weeks, he
      developed a rapidly worsening paranoid psychosis with visual and olfactory
      hallucinations. A month after the cessation of ethosuximide and concurrent
      treatment with olanzapine, his psychosis resolved and permitted reinitiation of
      ethosuximide at a lower dose without recurrence of psychotic symptoms.

PMID- 29222218
TI  - Fat embolism: a rare cause of perioperative renal transplant dysfunction.
AB  - Fat embolism is a recognised complication of bony injury and orthopaedic surgery,
      commonly involving the long bones and pelvis. We report on the case of a 68-year
      old renal transplant recipient who developed acute kidney injury following
      surgical stabilisation of metastatic carcinoma of the acetabulum and replacement
      of the proximal femur. A CT renal angiogram demonstrated a large fat embolus in
      the inferior vena cava (IVC) and left iliac veins below the level of IVC filter,
      with impaired renal perfusion. The risks of open or endovascular lipothrombectomy
      were felt to outweigh the potential benefits. The patient was managed with
      systemic anticoagulation and prepared for transplant failure. Subsequently, there
      was spontaneous improvement in urine output and 4 months postoperatively her
      transplant function had returned to her baseline level and this has remained
      stable at 1 year postsurgery.

PMID- 29222219
TI  - An uncommon diagnosis for a recurrent erythematous patch in a paediatric patient.
AB  - A 14-year-old girl presented with a circular erythematous patch over the left
      buttock for approximately 10 years, with ongoing ulceration and papules
      developing over the last 4 years. Punch biopsies were taken within and above the
      patch for diagnosis. Both revealed marked inflammatory infiltrates with atypical,
      irregular lymphocytes and increased mitosis. Immunostaining revealed CD8
      positivity and a pan T helper cell phenotype. T cell receptor gene rearrangement
      analysis showed T cell clonality in both biopsies. These findings were consistent
      with mycosisfungoides and associated lymphomatoid papulosis. Both are rare
      conditions but have been associated in 5%-20% of cases. A definitive association
      has not yet been established; however, T cell monoclonality shows 50%-60% share a
      common origin. Management options are extensive with no one treatment showing
      superiority. Our patient received low-dose radiotherapy with good outcomes, but
      subsequently required further radiotherapy.

PMID- 29222221
TI  - Acute pancreatitis following oesophagogastroduodenoscopy.
AB  - Acute pancreatitis is a well-recognised complication of endoscopic procedures
      like endoscopic retrograde cholangiopancreatography but not
      oesophagogastroduodenoscopy (OGD). I report a case of a 33-year-old woman,
      admitted with severe epigastric pain and vomiting 2 hours after an elective OGD
      for evaluation of chronic gastrointestinal symptoms. Pancreatitis was diagnosed
      on the basis of elevated lipase (40 790 U/L; normal 11-82) and findings on
      imaging studies. Other common causes of acute pancreatitis such as gallstones,
      alcohol and medications were ruled out. She had an extended hospital course
      because of severe disease, characterised by systemic inflammatory response
      syndrome, pleural effusion and ascites but was successfully managed
      conservatively with bowel rest, hydration and pain management. Acute pancreatitis
      should be considered a rare complication of OGD and should be considered in
      differential diagnosis for abdominal pain post OGD. Pathogenesis is likely from
      direct trauma to pancreas or gas insufflation.

PMID- 29222220
TI  - Pleural lipoma clinically mimicking the presentation of superior sulcus tumour
      upon initial evaluation.
AB  - Here we present a case of a large pleural lipoma which presented with
      paresthesias of the hand. This is an unusual presentation of an uncommon tumour.

PMID- 29222222
TI  - Inguinoscrotal herniation of a caecal adenocarcinoma.
AB  - An 84-year-old man with multiple comorbidities presented from a residential care
      home with a 1-month history of asthenia and moderate abdominal pain. On
      examination, he was found to have an irreducible right-sided inguinoscrotal
      hernia. Subsequent blood tests revealed a significant anaemia (haemoglobin 48
      g/L), for which he was transfused. A CT scan of the abdomen and pelvis revealed a
      large caecal tumour, herniating through the right inguinal canal into the
      scrotum. The patient underwent an elective open right hemicolectomy with inguinal
      hernia defect repair, from which he recovered well. He was discharged from the
      ward 12 days postoperatively and is awaiting outpatient follow-up.

PMID- 29222223
TI  - CSF ferritin predicts CSF Abeta decline in biomarker-determined Alzheimer's
      disease.

PMID- 29222224
TI  - Subthalamotomy for Parkinson's disease: clinical outcome and topography of
      lesions.
AB  - OBJECTIVE: Subthalamotomy is an effective alternative for the treatment of
      Parkinson's disease (PD). However, uncertainty about the optimal target location
      and the possibility of inducing haemichorea-ballism have limited its application.
      We assessed the correlation between the topography of radiofrequency-based
      lesions of the subthalamic nucleus (STN) with motor improvement and the emergence
      of haemichorea-ballism. METHODS: Sixty-four patients with PD treated with
      subthalamotomy were evaluated preoperatively and postoperatively using the
      Unified Parkinson's Disease Rating Scale motor score (UPDRSm), MRI and
      tractography. Patients were classified according to the degree of clinical motor
      improvement and dyskinesia scale. Lesions were segmented on MRI and averaged in a
      standard space. We examined the relationship between the extent of lesion-induced
      disruption of fibres surrounding the STN and the development of haemichorea
      ballism. RESULTS: Maximum antiparkinsonian effect was obtained with lesions
      located within the dorsolateral motor region of the STN as compared with those
      centre-placed in the dorsal border of the STN and the zona incerta (71.3%, 53.5%
      and 20.8% UPDRSm reduction, respectively). However, lesions that extended
      dorsally beyond the STN showed lower probability of causing haemichorea-ballism
      than those placed entirely within the nucleus. Tractography findings indicate
      that interruption of pallidothalamic fibres probably determines a low probability
      of haemichorea-ballism postoperatively. CONCLUSIONS: The topography of the lesion
      is a major factor in the antiparkinsonian effect of subthalamotomy in patients
      with PD. Lesions involving the motor STN and pallidothalamic fibres induced
      significant motor improvement and were associated with a low incidence of
      haemichorea-ballism.

PMID- 29222225
TI  - Letter by Rasmussen et al Regarding Article, "Anesthesia-Related Outcomes for
      Endovascular Stroke Revascularization: A Systematic Review and Meta-Analysis".

PMID- 29222226
TI  - Letter by Spence Regarding Article, "Serum Potassium Is Positively Associated
      With Stroke and Mortality in the Large, Population-Based Malmo Preventive Project
      Cohort".

PMID- 29222227
TI  - PINGS (Phone-Based Intervention Under Nurse Guidance After Stroke): Interim
      Results of a Pilot Randomized Controlled Trial.
AB  - BACKGROUND AND PURPOSE: Stroke exacts an immense toll in sub-Saharan Africa where
      there are few resources, and stroke prevention research is limited. The aim of
      this study is to test the feasibility and preliminary efficacy of an m-Health
      technology-enabled, nurse-guided intervention in improving blood pressure (BP)
      control among Ghanaian stroke patients within 1 month of symptom onset. METHODS:
      We conducted a 2-arm cluster pilot randomized controlled trial involving 60
      recent stroke survivors encountered within a single tertiary medical system in
      Ghana. Subjects in the intervention arm (n=30) received a Blue-toothed UA-767Plus
      BT BP device and smartphone for monitoring and reporting BP measurements and
      medication intake for 3 months compared with standard of care (n=30). Primary
      outcome measure was systolic BP <140 mm Hg at month 3; secondary outcomes
      included medication adherence and autonomous self-regulation. Analysis accounting
      for clustering was made using generalized linear mixed model by intention to
      treat. RESULTS: Mean+/-SD age was 55+/-13 years, 65% male. Systolic BP <140 mm Hg
      at month 3 was found in 20/30 subjects (66.7%) in the intervention arm versus
      14/30 subjects (46.7%) in the control arm (P=0.12). Medication possession ratio
      scores at month 3 were better in the intervention (0.88+/-0.40) versus control
      (0.64+/-0.45) arm (P=0.03). One subject in control arm died from a recurrent
      hemorrhagic stroke. CONCLUSIONS: It is feasible to conduct an m-Health-based,
      nurse-guided BP control intervention among recent stroke patients in sub-Saharan
      Africa. We observed a potential signal of efficacy with the intervention, which
      will need to be tested in a future large definitive study. CLINICAL TRIAL
      REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT02568137.

PMID- 29222228
TI  - Response by Brinjikji et al to Letter Regarding Article, "Anesthesia-Related
      Outcomes for Stroke Revascularization: A Systematic Review and Meta-Analysis".

PMID- 29222229
TI  - Visual Aids for Patient, Family, and Physician Decision Making About Endovascular
      Thrombectomy for Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Rapid decision making optimizes outcomes from
      endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate
      swift review of potential outcomes and can accelerate decision processes.
      METHODS: From patient-level, pooled randomized trial data, 100 person-icon arrays
      (Kuiper-Marshall personographs) were generated showing beneficial and adverse
      effects of endovascular thrombectomy for patients with acute cerebral ischemia
      and large vessel occlusion using (1) automated (algorithmic) and (2) expert
      guided joint outcome table specification. RESULTS: For the full 7-category
      modified Rankin Scale, thrombectomy added to IV tPA (intravenous tissue-type
      plasminogen activator) alone had number needed to treat to benefit 2.9 (95%
      confidence interval, 2.6-3.3) and number needed to harm 68.9 (95% confidence
      interval, 40-250); thrombectomy for patients ineligible for IV tPA had number
      needed to treat to benefit 2.3 (95% confidence interval, 2.1-2.5) and number
      needed to harm 100 (95% confidence interval, 62.5-250). Visual displays of
      treatment effects on 100 patients showed: with thrombectomy added to IV tPA
      alone, 34 patients have better disability outcome, including 14 more normal or
      near normal (modified Rankin Scale, 0-1); with thrombectomy for patients
      ineligible for IV tPA, 44 patients have a better disability outcome, including 16
      more normal or nearly normal. Displays also showed that harm (increased modified
      Rankin Scale final disability) occurred in 1 of 100 patients in both populations,
      mediated by increased new territory infarcts. The person-icon figures integrated
      these outcomes, and early side-effects, in a single display. CONCLUSIONS: Visual
      decision aids are now available to rapidly educate healthcare providers,
      patients, and families about benefits and risks of endovascular thrombectomy,
      both when added to IV tPA in tPA-eligible patients and as the sole reperfusion
      treatment in tPA-ineligible patients.

PMID- 29222230
TI  - Response by Johnson and Soderholm to Letter Regarding Article, "Serum Potassium
      Is Positively Associated With Stroke and Mortality in the Large, Population-Based
      Malmo Preventive Project Cohort".

PMID- 29222231
TI  - AL amyloidosis: from molecular mechanisms to targeted therapies.
AB  - Systemic amyloidosis is caused by misfolding and extracellular deposition of
      circulating proteins as amyloid fibrils, resulting in the dysfunction of vital
      organs. The most common systemic amyloidosis, light-chain (AL) amyloidosis, is
      caused by misfolded light chains produced by a small, dangerous B-cell clone. The
      process of amyloid formation, organ targeting, and damage is multifaceted and,
      after disease initiation, the complexity of the downstream pathogenic cascade
      increases, rendering its control a challenge. Because of the progressive nature
      of the disease, early diagnosis to prevent end-stage organ damage is vital.
      Improving awareness and systematic use of biomarkers of organ damage in screening
      populations at risk may improve the still unsatisfactory diagnostic process.
      Amyloid imaging is now emerging as an important companion of biomarkers in
      formulating the diagnosis and prognosis and monitoring the effects of therapy. An
      accurate diagnosis is the basis for appropriate therapy that is risk-adapted and
      response-tailored. Effective treatments targeting the clone and rapidly and
      profoundly reducing the amyloid light chains have produced marked improvements in
      overall survival, making AL amyloidosis the most successful model of all
      amyloidoses. New therapies targeting the amyloid deposits are now under
      development, together with novel agents modulating light chain aggregation and
      proteotoxicity. The future of AL amyloidosis treatment is combination therapy and
      will require an innovative collaborative model for a rapid translation from bench
      to bedside with the ultimate aim of achieving a cure for this complex disease.

PMID- 29222232
TI  - Minimal residual disease in adult ALL: technical aspects and implications for
      correct clinical interpretation.
AB  - Nowadays, minimal residual disease (MRD) is accepted as the strongest independent
      prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by
      molecular methods that use leukemia-specific or patient-specific molecular
      markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene
      rearrangements), and by multi-parametric flow cytometry. The sensitivity and
      specificity of these methods can vary across treatment time points and
      therapeutic settings. Thus, knowledge of the principles and limitations of each
      technology is of the utmost importance for correct interpretation of MRD results.
      Time will tell whether new molecular and flow cytometric high-throughput
      technologies can overcome the limitations of current standard methods and
      eventually bring additional benefits. MRD during standard ALL chemotherapy is the
      strongest overall prognostic indicator and has therefore been used for refining
      initial treatment stratification. Moreover, MRD positivity after the maintenance
      phase of treatment may point to an impending relapse and thus enable salvage
      treatment to be initiated earlier, which could possibly improve treatment
      results. The prognostic relevance of pretransplantation MRD was shown by several
      studies, and MRD high-risk patients were shown to benefit from stem cell
      transplantation (SCT). Also, MRD positivity after SCT correlates with worse
      outcomes. In addition, MRD information is very instructive in current clinical
      trials that test novel agents to evaluate their treatment efficacy. Although
      conventional clinical risk factors lose their independent prognostic significance
      when combined with MRD information, recently identified genetic markers may
      further improve the treatment stratification in ALL.

PMID- 29222233
TI  - Current management of Philadelphia chromosome positive ALL and the role of stem
      cell transplantation.
AB  - Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia
      exemplifies how the addition of potent targeted agents, directed at the molecular
      aberrations responsible for leukemic transformation, can overcome resistance
      mechanisms to traditional regimens and lead to improved outcomes. The
      introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has
      significantly improved the outcomes not only by allowing more patients to undergo
      allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing
      our reliance on this potentially toxic strategy, particularly in the less fit
      population. Long-term data using chemotherapy and TKI combinations demonstrate
      that a proportion of patients treated can achieve durable relapse-free survival
      without undergoing alloHCT. Furthermore, the availability of sensitive minimal
      residual disease monitoring assays may allow early detection of the patients who
      are more likely to relapse and who are likely candidates for early alloHCT. The
      emergence of more potent TKIs with significant activity against resistant
      mutations has allowed deintensification of chemotherapy regimens. Available data
      indicate that complete reliance on TKIs, alone or with minimal additional
      therapy, and elimination of more intensive chemotherapy or alloHCT is unlikely to
      achieve long term cure in most patients. However, introduction of other highly
      effective agents that can be combined with TKIs may allow further minimization of
      chemotherapy and alloHCT in the future, as we have witnessed in acute
      promyelocytic leukemia.

PMID- 29222234
TI  - Progress in adult ALL: incorporation of new agents to frontline treatment.
AB  - Treatment of acute lymphoblastic leukemia (ALL) in adults remains a challenge, as
      the delivery of intensive chemotherapeutic regimens in this population is less
      feasible than it is in the pediatric population. This has led to higher rates of
      treatment-related toxicity as well as lower overall survival in the adult
      population. Over the past several years, a host of novel therapies (eg,
      immunotherapy and targeted therapies) with better tolerability than traditional
      chemotherapy are now being introduced into the relapsed/refractory population
      with very encouraging results. Additionally, insights into how to choose
      effective therapies for patients while minimizing drug toxicity through
      pharmacogenomics and the use of minimal residual disease (MRD) monitoring to
      escalate/de-escalate therapy have enhanced our ability to reduce treatment
      related toxicity. This has led to the design of a number of clinical trials which
      incorporate both novel therapeutics as well as MRD-directed treatment pathways
      into the frontline setting. The use of increasingly personalized treatment
      strategies for specific disease subsets combined with standardized and rapid
      molecular diagnostic testing in the initial diagnosis and frontline treatment of
      ALL will hopefully lead to further improvements in survival for our adult
      patients.

PMID- 29222235
TI  - Classification and risk assessment in AML: integrating cytogenetics and molecular
      profiling.
AB  - In recent years, the composite molecular architecture in acute myeloid leukemia
      (AML) has been mapped out. We now have a clearer understanding of the key genetic
      determinants, the major genetic interactions, and the broad order in which these
      mutations occur. The next impending challenge is to discern how these recent
      genomic discoveries define disease biology as well as how to use molecular
      markers to deliver patient-tailored clinical decision support.

PMID- 29222236
TI  - How and when to decide between epigenetic therapy and chemotherapy in patients
      with AML.
AB  - Remission induction with chemotherapy has long been the frontline treatment of
      acute myeloid leukemia (AML). However, intensive therapy is limited in frail
      patients by its associated toxicity and higher rates of failure or relapse in
      patients with chemoresistant disease, such as secondary AML or poor-risk
      cytogenetics. Frailty and chemoresistance are more frequent in older adults with
      AML. In recent years, epigenetic therapies with the hypomethylating agents
      decitabine and azacitidine have been thoroughly explored in AML. The results of
      two pivotal studies carried out with these agents in older adults with newly
      diagnosed AML have challenged the role of intensive chemotherapy as the frontline
      treatment option in this high-risk population. Here, we review the results of
      treatment with intensive chemotherapy and hypomethylating agents in older
      patients with AML; discuss the patient- and disease-specific criteria to
      integrate into treatment decision making; and also, highlight the methodological
      limitations of cross-study comparison in this population.

PMID- 29222237
TI  - The role of targeted therapy in the management of patients with AML.
AB  - Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes
      in 2017. This is due to the US Food and Drug Administration's approval of several
      new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired
      with the recent approval of a novel liposomal formulation of
      daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing
      rapidly in AML for subgroups. This review will focus on currently approved agents
      and promising novel agents in development and will highlight controversial areas
      in targeted treatment.

PMID- 29222238
TI  - Clinical implications of somatic mutations in aplastic anemia and myelodysplastic
      syndrome in genomic age.
AB  - Recent technological advances in genomics have led to the discovery of new
      somatic mutations and have brought deeper insights into clonal diversity. This
      discovery has changed not only the understanding of disease mechanisms but also
      the diagnostics and clinical management of bone marrow failure. The clinical
      applications of genomics include enhancement of current prognostic schemas,
      prediction of sensitivity or refractoriness to treatments, and conceptualization
      and selective application of targeted therapies. However, beyond these
      traditional clinical aspects, complex hierarchical clonal architecture has been
      uncovered and linked to the current concepts of leukemogenesis and stem cell
      biology. Detection of clonal mutations, otherwise typical of myelodysplastic
      syndrome, in the course of aplastic anemia (AA) and paroxysmal nocturnal
      hemoglobinuria has led to new pathogenic concepts in these conditions and created
      a new link between AA and its clonal complications, such as post-AA and
      paroxysmal nocturnal hemoglobinuria. Distinctions among founder vs subclonal
      mutations, types of clonal evolution (linear or branching), and biological
      features of individual mutations (sweeping, persistent, or vanishing) will allow
      for better predictions of the biologic impact they impart in individual cases. As
      clonal markers, mutations can be used for monitoring clonal dynamics of the stem
      cell compartment during physiologic aging, disease processes, and leukemic
      evolution.

PMID- 29222239
TI  - Aging, hematopoiesis, and the myelodysplastic syndromes.
AB  - The aging hematopoietic system undergoes numerous changes, including reduced
      production of red blood cells and lymphocytes as well as a relative increase in
      the production of myeloid cells. Emerging evidence indicates that many of these
      changes are due to selection pressures from cell-intrinsic and cell-extrinsic
      factors that result in clonal shifts in the hematopoietic stem cell (HSC) pool,
      resulting in predominant HSC clones that exhibit the functional characteristics
      associated with HSC aging. Given the recent descriptions of clonal hematopoiesis
      in aged populations, the increased risk of developing hematologic malignancies in
      individuals with clonal hematopoiesis, and the many similarities in hematopoietic
      aging and acquired bone marrow failure (BMF) syndromes, such as myelodysplastic
      syndromes (MDS), this raises significant questions regarding the relationship
      between aging hematopoiesis and MDS, including the factors that regulate HSC
      aging, whether clonal hematopoiesis is required for the development of MDS, and
      even whether BMF is an inevitable consequence of aging. In this article, we will
      review our current understanding of these processes and the potential
      intersections among them.

PMID- 29222240
TI  - Old and new tools in the clinical diagnosis of inherited bone marrow failure
      syndromes.
AB  - Patients with inherited bone marrow failure syndromes (IBMFSs) classically
      present with specific patterns of cytopenias along with congenital anomalies
      and/or other physical features that are often recognizable early in life.
      However, increasing application of genomic sequencing and clinical awareness of
      subtle disease presentations have led to the recognition of IBMFS in pediatric
      and adult populations more frequently than previously realized, such as those
      with early onset myelodysplastic syndrome (MDS). Given the well-defined
      differences in clinical management needs and outcomes for aplastic anemia, acute
      myeloid leukemia, and MDS in patients with an IBMFS vs those occurring
      sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it
      is critical for hematologists to understand how to approach screening for the
      currently known IBMFSs. This review presents a practical approach for the
      clinical hematologist that outlines when to suspect an IBMFS and how to use
      various diagnostic tools, from physical examination to screening laboratory tests
      and genomics, for the diagnosis of the most frequent IBMFSs: Fanconi anemia,
      telomere biology disorders, Diamond-Blackfan anemia, GATA2 deficiency syndrome,
      Shwachman-Diamond syndrome, and severe congenital neutropenia.

PMID- 29222241
TI  - Inherited bone marrow failure syndromes: considerations pre- and posttransplant.
AB  - Patients with inherited bone marrow failure syndromes are usually identified when
      they develop hematologic complications such as severe bone marrow failure,
      myelodysplastic syndrome, or acute myeloid leukemia. They often have specific
      birth defects or other physical abnormalities that suggest a syndrome, and
      sequencing of specific genes or next-generation sequencing can determine or
      confirm the particular syndrome. The 4 most frequent syndromes are Fanconi
      anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond
      syndrome. This review discusses the major complications that develop as the
      patients with these syndromes age, as well as additional late effects following
      hematopoietic stem cell transplantation. The most common complications are iron
      overload in transfused patients and syndrome-specific malignancies in
      untransplanted patients, which may occur earlier and with higher risks in those
      who have received transplants.

PMID- 29222242
TI  - Treatment of inherited bone marrow failure syndromes beyond transplantation.
AB  - Despite significant progress in transplantation by the addition of alternative
      hematopoietic stem cell sources, many patients with inherited bone marrow failure
      syndromes are still not eligible for a transplant. In addition, the availability
      of sequencing panels has significantly improved diagnosis by identifying cryptic
      inherited cases. Androgens are the main nontransplant therapy for bone marrow
      failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to
      80% of cases. Danazol and oxymetholone are more commonly used, but virilization
      and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly
      treated with corticosteroids, but most patients eventually become refractory to
      this treatment and toxicity is limiting. Growth factors still have a role in
      inherited cases, especially granulocyte colony-stimulating factor in congenital
      neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists,
      leucine, quercetin, and novel gene therapy approaches may benefit inherited cases
      in the future.

PMID- 29222243
TI  - Treatment-free remission in CML: who, how, and why?
AB  - Chronic myeloid leukemia (CML) is the best example of successful targeted
      therapy. Today, the overall survival of patients with CML treated by using
      tyrosine kinase inhibitors (TKIs) is very close to that of the healthy
      population. The current question is: how can we further ameliorate the clinical
      outcome of patients with CML? Clinical trials have shown that some patients with
      CML in the chronic phase who achieve sustained deep molecular responses on TKI
      therapy can safely suspend therapy with no evidence of relapse. The long follow
      up studies and the number of eligible patients have now validated the concept of
      treatment-free remission (ie, the ability to maintain a molecular response after
      stopping therapy). It should be considered as the future criterion to evaluate
      the success of clinical trials, especially if we want to take into account the
      quality of life of patients in addition to the economic aspect. Because post-TKI
      discontinuation follow-ups have been increasing over time with no evidence of
      relapse in some patients, the next step for the coming decade will be to address
      the topic of CML cure.

PMID- 29222244
TI  - Cardiovascular care of patients with chronic myeloid leukemia (CML) on tyrosine
      kinase inhibitor (TKI) therapy.
AB  - Cardiovascular (CV) health has emerged as an important consideration in patients
      with chronic myeloid leukemia (CML) because of improved prognosis. Indeed, the
      success of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has increased the focus on
      survivorship and late toxicity in oncological care. Survivorship issues in this
      population include CV disease prevention, given its prevalence in the general
      population. The introduction of BCR-ABL1 TKIs represented a unique concept of
      indefinite cancer therapy, only recently evolving to include "treatment-free
      remission." Importantly, later-generation BCR-ABL1 TKIs have been associated with
      CV complications. Dasatinib has been associated with pleural/pericardial
      effusions and pulmonary hypertension, whereas nilotinib and ponatinib have been
      linked to the development of vascular occlusive events. There is currently a
      dearth of data with respect to the mechanisms of drug toxicities, the subsets of
      patients at risk, and prevention and treatment strategies to mitigate CV
      complications in patients with CML. Nevertheless, optimal patient CV risk
      assessment needs to become a more central tenet of patient care in CML. We
      propose several practical considerations for the practicing oncologist relative
      to the CV health of patients with CML, especially those on chronic TKI therapy.

PMID- 29222245
TI  - Novel approaches to therapy in CML.
AB  - Treatment with tyrosine kinase inhibitors (TKIs) results in remission and
      prolongation of survival in most chronic myeloid leukemia (CML) patients but
      fails to eliminate the leukemia stem cells (LSCs) responsible for disease
      development and propagation. This accounts for the clinical observation that TKI
      discontinuation leads to rapid leukemia relapse. Most patients require continued
      treatment to prevent relapse, with associated risk of relapse, toxicity,
      teratogenic effects, financial burden, and noncompliance. Understanding LSC
      resistance to TKI and development of strategies to increase the proportion of CML
      patients achieving treatment-free remissions is a critical area of investigation
      in CML. In addition, LSCs are the source of TKI resistance, relapse, or disease
      progression, which is another major area of need in CML treatment. It is now
      understood that BCR-ABL kinase-independent mechanisms are responsible for
      retention of LSC subpopulations. It is likely that both cell-intrinsic and
      microenvironmental mechanisms contribute to LSC maintenance. Here, we review the
      current understanding of mechanisms underlying persistence of CML LSCs during TKI
      treatment, recently described approaches to target these cells and emerging
      clinical trials, and the challenges impeding more rapid progress in achieving
      cures for a greater number of CML patients.

PMID- 29222246
TI  - Incidental venous thromboembolism: is anticoagulation indicated?
AB  - Patients with cancer have a high risk of venous thromboembolism (VTE) and about
      one-half of these events are incidentally detected. The prognosis of incidental
      VTE appears to be similar to symptomatic events, with comparably high rates of
      recurrent VTE in this patient population. In the absence of major
      contraindications, anticoagulant treatment with low-molecular-weight heparin for
      3 to 6 months is generally recommended for incidental proximal deep vein
      thrombosis as well as for incidental pulmonary embolism that involves multiple
      subsegmental or more proximal pulmonary arteries. The decision of whether to
      extend treatment beyond 3 to 6 months should be evaluated on a case-by-case basis
      after periodic reassessment of the risks factors for bleeding and recurrent VTE
      while also taking into account patient preferences. The clinical relevance of a
      single incidental subsegmental pulmonary embolism without concomitant deep vein
      thrombosis is uncertain and either a watchful approach or a shorter course of
      anticoagulation to minimize the bleeding risk may also be considered. Preliminary
      evidence suggests that anticoagulation treatment may be beneficial for cancer
      patients with incidental distal deep vein thrombosis or incidental splanchnic
      vein thrombosis.

PMID- 29222247
TI  - When can we stop anticoagulation in patients with cancer-associated thrombosis?
AB  - The optimal duration of anticoagulant therapy in patients with cancer-associated
      venous thromboembolism (VTE) is unknown. Without well-designed studies evaluating
      the efficacy, safety, and cost-effectiveness of continuing anticoagulant therapy
      beyond the acute treatment period of 3 to 6 months, evidence-based
      recommendations are lacking. Consensus guidelines generally suggest continuing
      anticoagulation treatment in patients with active cancer or receiving cancer
      treatment, with periodic reassessment of the risks and benefits. Unfortunately,
      with very little published data on the epidemiology of cancer-associated VTE
      beyond the initial 6 months, it is not possible for clinicians and patients to
      weigh risks and benefits in a quantitatively informed manner. Further research is
      needed to provide reliable and contemporary estimates on the risk of recurrent
      VTE off anticoagulant therapy, risk of bleeding on anticoagulant therapy, case
      fatality or all-cause mortality, and other important consequences of living with
      cancer-associated VTE. This chapter provides an overview of the published
      literature on real-world data on anticoagulant therapy use, the risks and risk
      factors of recurrent VTE and bleeding, and patient preference and values
      regarding long-term anticoagulation treatment. It will conclude with a pragmatic,
      experience-informed approach for tailoring anticoagulant therapy in patients with
      cancer-associated VTE.

PMID- 29222248
TI  - Direct oral anticoagulants: now also for prevention and treatment of cancer
      associated venous thromboembolism?
AB  - Data on specific studies in cancer patients using direct oral anticoagulants
      (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are
      still scarce. For preventing VTE with DOACs, current experience is still very
      limited, so definite conclusions cannot yet be drawn. However, DOACs have so far
      been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5
      studies, and several hundreds of patients included in these studies had either
      active cancer, a history of cancer, or a new occurrence of cancer during the
      course of disease. Meta-analyses have revealed an at least similar efficacy and
      safety profile of DOACs compared with VKAs. A number of studies of cancer
      patients investigating primary prevention and treatment are underway, and some
      will be finalized soon. Nevertheless, we might need further trials, specifically
      on the prevention of VTE in patients who are at particularly high risk. This
      article also includes a personal opinion on the use of DOACs in cancer patients.
      In conclusion, the currently available data show that DOACs might be safe and
      efficacious in the treatment of VTE, however, this has yet to be proven in
      specifically designed trials in patients with cancer. With regard to prevention,
      thus far, even less data exist, and the outcomes of the ongoing studies have to
      be evaluated before DOACs may be used for primary prevention.

PMID- 29222250
TI  - Iron deficiency in gynecology and obstetrics: clinical implications and
      management.
AB  - Iron deficiency is the commonest cause of anemia during pregnancy; however, its
      prevalence is highly determined by nutritional and socioeconomic status. Oral
      iron is the frontline therapy, but is often poorly tolerated. Awareness of the
      available intravenous formulations is essential for management. Before delivery,
      risk factors such as multiparity and heavy uterine bleeding increase the
      prevalence of iron deficiency and should be motivation for early diagnosis and
      treatment. Neonates born with iron deficiency have a statistically significant
      increment in both cognitive and behavioral abnormalities that persist after
      repletion, highlighting the need for heightened awareness of the diagnosis. A
      smartphone application providing information on nutrition and treatment is
      provided. New formulations of intravenous iron with carbohydrate cores, which
      bind elemental iron more tightly, minimize the release of labile free iron to
      allow complete replacement doses of intravenous iron in 15 to 60 minutes,
      facilitating and simplifying care.

PMID- 29222249
TI  - Thrombocytopenia in pregnancy.
AB  - Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the
      immediate postpartum period. A low platelet count is often an incidental feature,
      but it might also provide a biomarker of a coexisting systemic or gestational
      disorder and a potential reason for a maternal intervention or treatment that
      might pose harm to the fetus. This chapter reflects our approach to these issues
      with an emphasis on advances made over the past 5 to 10 years in understanding
      and managing the more common causes of thrombocytopenia in pregnancy. Recent
      trends in the management of immune thrombocytopenia translate into more women
      contemplating pregnancy while on treatment with thrombopoietin receptor agonists,
      rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New
      criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13
      to make management decisions in suspected thrombotic thrombocytopenic purpura,
      new evidence supporting the efficacy and safety of anticomplement therapy for
      atypical hemolytic uremic syndrome during pregnancy, and implications of
      thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The
      goals of the chapter are to help the hematology consultant work through the
      differential diagnosis of thrombocytopenia in pregnancy based on trimester of
      presentation, severity of thrombocytopenia, and coincident clinical and
      laboratory manifestations, and to provide guidance for dealing with some of the
      more common and difficult diagnostic and management decisions.

PMID- 29222251
TI  - Preventing venous thromboembolism during pregnancy and postpartum: crossing the
      threshold.
AB  - When should a patient with a known thrombophilia or prior venous thromboembolism
      (VTE) receive low-molecular-weight heparin (LMWH) prophylaxis during pregnancy
      and/or the postpartum period? Accurately predicting thrombotic and bleeding risks
      and knowing what to do with this information is at the heart of decision-making
      in these challenging scenarios. This article will explore the concept of a risk
      threshold from clinician and patient perspectives and provide guidance for the
      use of antepartum and postpartum LMWH prophylaxis in women with a known
      thrombophilia or prior VTE. Advice for the management of LMWH prophylaxis use
      around labor and delivery is also reviewed.

PMID- 29222252
TI  - Diagnosis and management of postpartum ovarian vein thrombosis.
AB  - CASE PRESENTATION: A 26-year-old woman experienced persistent fever (39.5 degrees
      C), chills, and right-lower-quadrant tenderness 3 days after caesarean delivery.
      A computed tomography (CT) scan of the abdomen and pelvis with contrast revealed
      enlargement of her right ovarian vein with an associated intraluminal filling
      defect. What is the best treatment of this patient?

PMID- 29222253
TI  - New monogenic disorders identify more pathways to neutropenia: from the clinic to
      next-generation sequencing.
AB  - Neutrophils are the most common type of leukocyte in human circulating blood and
      constitute one of the chief mediators for innate immunity. Defined as a reduction
      from a normal distribution of values, neutropenia results from a number of
      congenital and acquired conditions. Neutropenia may be insignificant, temporary,
      or associated with a chronic condition with or without a vulnerability to life
      threatening infections. As an inherited bone marrow failure syndrome, neutropenia
      may be associated with transformation to myeloid malignancy. Recognition of an
      inherited bone marrow failure syndrome may be delayed into adulthood. The list of
      monogenic neutropenia disorders is growing, heterogeneous, and bewildering.
      Furthermore, greater knowledge of immune-mediated and drug-related causes makes
      the diagnosis and management of neutropenia challenging. Recognition of syndromic
      presentations and especially the introduction of next-generation sequencing are
      improving the accuracy and expediency of diagnosis as well as their clinical
      management. Furthermore, identification of monogenic neutropenia disorders is
      shedding light on the molecular mechanisms of granulopoiesis and myeloid
      malignancies.

PMID- 29222254
TI  - Chronic neutropenia in LGL leukemia and rheumatoid arthritis.
AB  - This section reviews the diagnostic criteria and pathogenesis of large granular
      lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL
      leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of
      the mechanisms of neutropenia in these disorders is discussed. Finally, treatment
      indications and therapeutic recommendations are outlined.

PMID- 29222256
TI  - Shall we treat smoldering multiple myeloma in the near future?
AB  - In recent years, several new drugs have been approved for the treatment of
      multiple myeloma. Many of these newer drugs are highly efficacious and less toxic
      than older chemotherapy drugs. In 2014, the diagnostic criteria for multiple
      myeloma were revised. The intent with the new criteria was to identify patients
      who require therapy at an earlier stage than at manifestation of organ
      complications. A subset of patients who were previously defined as having high
      risk smoldering multiple myeloma was redefined as having multiple myeloma. In
      this context, it is logical to raise questions regarding the optimal clinical
      management of patients who are diagnosed with smoldering multiple myeloma in the
      current era. When is the optimal time to start therapy? Do the clinical
      trajectories for patients suggest there are distinct sub-entities hidden in the
      current category of smoldering multiple myeloma? How can we move the field
      forward from here? This paper reviews and dissects data and models on the topics
      of clinical features, underlying biology, and early treatment trials in
      smoldering multiple myeloma. The text highlights assumptions, facts, and gaps in
      the literature. As indicated in the title of the paper, the recurrent theme of
      the text is this: shall we treat smoldering multiple myeloma in the near future?

PMID- 29222255
TI  - Non-chemotherapy drug-induced neutropenia: key points to manage the challenges.
AB  - Non-chemotherapy idiosyncratic drug-induced neutropenia (IDIN) is a relatively
      rare but potentially fatal disorder that occurs in susceptible individuals, with
      an incidence of 2.4 to 15.4 cases per million population. Affected patients
      typically experience severe neutropenia within several weeks to several months
      after first exposure to a drug, and mortality is ~5%. The drugs most frequently
      associated with IDIN include metamizole, clozapine, sulfasalazine, thiamazole,
      carbimazole, amoxicillin, cotrimoxazole, ticlopidine, and valganciclovir. The
      idiosyncratic nature of IDIN, the lack of mouse models and diagnostic testing,
      and its low overall incidence make rigorous studies to elucidate possible
      mechanisms exceptionally difficult. An immune mechanism for IDIN involving
      neutrophil destruction by hapten (drug)-specific antibodies and drug-induced
      autoantibodies is frequently suggested, but strong supporting evidence is
      lacking. Although laboratory testing for neutrophil drug-dependent antibodies is
      rarely performed because of the complexity and low sensitivity of tests currently
      in use, these assays could possibly be enhanced by using reactive drug
      metabolites in place of the parent drug. Patients typically experience acute,
      severe neutropenia, or agranulocytosis (<0.5 * 109 neutrophils/L) and symptoms of
      fever, chills, sore throat, and muscle and joint pain. Diagnosis can be
      difficult, but timely recognition is critical because if left untreated, there is
      an increase in mortality. Expanded studies of the production and mechanistic role
      of reactive drug metabolites, genetic associations, and improved animal models of
      IDIN are essential to further our understanding of this important disorder.

PMID- 29222257
TI  - Is molecular remission the goal of multiple myeloma therapy?
AB  - The increased number of effective therapies and the wider use of combinations
      that give deeper remissions have resulted in a reassessment of the goals of
      myeloma therapy. With the advent of new therapeutic strategies and diagnostic
      tools, achievement of minimal residual disease (MRD)-negative status has become
      increasingly important, with some even considering it as the primary endpoint for
      therapy. The level of MRD that is aimed for is a continuous, rather than an
      absolute variable, with studies in both transplant-eligible and -noneligible
      patients showing that the level of MRD achieved is predictive of progression-free
      survival and overall survival, with an improvement in survival of approximately 1
      year for each log-depletion in MRD level. The most widely used methods to assess
      MRD status include flow cytometry and clonality detection, using next-generation
      sequencing technologies with sensitivity limits of 1:10-3 to 1:10-6 The timing of
      when to assess MRD depends on the treatment used, as well as the molecular and
      cytogenetic subgroup of the myeloma itself. It is also becoming clear that the
      level of MRD negativity, as well as microenvironmental factors, are important
      prognostically, including the regeneration of normal plasma cells, and the
      normalization of the immune repertoire. With advances in antibody-based therapy
      and immunotherapy, the achievement of stable MRD states is now possible for a
      significant proportion of patients, and is a prerequisite for myeloma cure.

PMID- 29222259
TI  - Controversies in venous thromboembolism: to treat or not to treat superficial
      vein thrombosis.
AB  - The management of superficial vein thrombosis (SVT) is poorly defined and remains
      controversial overall. SVT has long been considered a benign, self-limited
      disease, but recent studies show that SVT carries a nonnegligible risk for
      recurrence, deep vein thrombosis, or pulmonary embolism. Current guidelines
      recommend the use of low-molecular-weight heparin or fondaparinux, but results of
      several surveys indicate that the majority of patients with SVT receive
      nonanticoagulant therapy only, which includes compression stockings or bandages,
      nonsteroidal anti-inflammatory drugs, topical application of heparin gel, or
      surgical interventions. However, several recent observational and interventional
      studies provide better insight into the optimal treatment of patients with SVT
      who are at different risks for thromboembolic complications. This educational
      review summarizes the available evidence and aims to provide practical guidance
      based on a clinical decision pathway.

PMID- 29222258
TI  - Fixed duration vs continuous therapy in multiple myeloma.
AB  - The introduction of new drugs with less severe toxicity profiles than those of
      conventional antimyeloma agents allowed the evaluation of continuous therapy
      compared with fixed duration therapy. In transplant-eligible patients,
      consolidation therapy with bortezomib or bortezomib-based regimens showed
      significant progression-free survival (PFS) benefit in cytogenetic standard-risk
      patients and to a lesser extent, high-risk patients. Continuous therapy with
      lenalidomide maintenance treatment after autologous stem cell transplantation
      resulted in a significant survival gain. In transplant noneligible patients,
      continuous lenalidomide-dexamethasone therapy improved survival over fixed
      duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in
      elderly patients is supported by some other studies, but most of them revealed a
      gain in PFS only. Young patients with unfavorable prognosis show a greater
      willingness to accept long-term treatment, whereas the readiness to undergo such
      treatments and the benefits therefrom decline with increasing age and decreasing
      fitness, rendering fixed duration therapy a suitable option in elderly frail
      patients.

PMID- 29222260
TI  - Should we diagnose and treat distal deep vein thrombosis?
AB  - Ultrasound series report that isolated distal deep vein thrombosis (DVT), also
      known as calf DVT, represents up to 50% of all lower-limb DVTs and, therefore, is
      a frequent medical condition. Unlike proximal DVT and pulmonary embolism, which
      have been studied extensively and for which management is well standardized, much
      less is known about the optimal management of isolated calf DVT. Recent data
      arising from registries and nonrandomized studies have suggested that most distal
      DVTs do not extend to the proximal veins and have an uneventful follow-up when
      left untreated. These data had some impact on the international recommendations
      that recently stated that ultrasound surveillance instead of systematic
      therapeutic anticoagulation might be an option for selected low-risk patients.
      However, robust data from randomized studies are scarce. Only 5 randomized trials
      assessing the need for anticoagulation for calf DVT have been published. Many of
      these trials had an open-label design and were affected by methodological
      limitations. The only randomized placebo-controlled trial included low-risk
      patients (outpatients without cancer or previous venous thromboembolism [VTE])
      and was hampered by limited statistical power. Nevertheless, data from this trial
      confirmed that the use of therapeutic anticoagulation in low-risk patients with
      symptomatic calf DVT is not superior to placebo in reducing VTE but is associated
      with a significantly higher risk of bleeding. Further randomized studies are
      needed to define the best therapy for high-risk patients (inpatients, patients
      with active cancer, or patients with previous VTE) and the optimal dose and
      duration of treatment.

PMID- 29222261
TI  - Symptomatic subsegmental pulmonary embolism: to treat or not to treat?
AB  - The introduction of computed tomographic pulmonary angiography and its recent
      increasing availability has led to a significant rise in its use to help
      clinicians diagnose acute pulmonary embolism (PE). This has led to a significant
      increase in the incidence of PE diagnoses. Simultaneously, the case fatality rate
      of acute PE has been decreasing and no significant change in its mortality has
      been noted, suggesting that the additional PE diagnoses are less severe and these
      patients might not benefit from anticoagulation therapy. This also seems to be
      correlated with an increase in the diagnosis of PE localized in the subsegmental
      pulmonary arteries (subsegmental pulmonary embolism [SSPE]). The clinical
      importance of SSPE is unclear. Whereas some studies have shown that it might be
      reasonable to manage patients with SSPE without anticoagulation, others have not.
      Although the current medical literature is limited, it suggests that a subgroup
      of patients with SSPE might be safely managed without the use of anticoagulant
      therapy. Current clinical practice guidelines suggest that clinicians take an
      individualized approach after carefully assessing the risk/benefit ratio for
      patients with SSPE and negative leg limb ultrasonography results. Prospective
      studies are ongoing and results are eagerly awaited to help tailor the management
      of this patient population.

PMID- 29222262
TI  - Pediatric leukemia susceptibility disorders: manifestations and management.
AB  - The clinical manifestations of inherited susceptibility to leukemia encompass a
      wide phenotypic range, including patients with certain congenital anomalies or
      early-onset myelodysplastic syndrome (MDS) and some with no obvious medical
      problems until they develop leukemia. Leukemia susceptibility syndromes occur as
      a result of autosomal dominant, autosomal recessive, or X-linked recessive
      inheritance, or de novo occurrence, of germline pathogenic variants in DNA
      repair, ribosome biogenesis, telomere biology, hematopoietic transcription
      factors, tumor suppressors, and other critical cellular processes. Children and
      adults with cytopenias, MDS, dysmorphic features, notable infectious histories,
      immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity
      to radiation or chemotherapy, or acute leukemia with a family history of early
      onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly
      evaluated for a leukemia susceptibility syndrome. Genetic testing and other
      diagnostic modalities have improved our ability to identify these patients and to
      counsel them and their family members for subsequent disease risk, cancer
      surveillance, and therapeutic interventions. Herein, the leukemia susceptibility
      syndromes are divided into 3 groups: (1) those associated with an underlying
      inherited bone marrow failure syndrome, (2) disorders in which MDS precedes
      leukemia development, and (3) those with a risk primarily of leukemia. Although
      children are the focus of this review, it is important for clinicians to
      recognize that inherited susceptibility to cancer can present at any age, even in
      older adults; genetic counseling is essential and prompt referral to experts in
      each syndrome is strongly recommended.

PMID- 29222263
TI  - Crisis management in the treatment of childhood acute lymphoblastic leukemia:
      putting right what can go wrong (emergency complications of disease and
      treatment).
AB  - The improvement in overall survival in children with acute lymphoblastic leukemia
      (ALL) over the last 5 decades has been considerable, with around 90% now
      surviving long term. The risk of relapse has been reduced to such an extent that
      the risk of treatment-related mortality is now approaching that of mortality
      caused by relapse. Toxicities may also lead to the suboptimal delivery of
      chemotherapy (treatment delays, dose reductions, dose omissions), potentially
      increasing relapse risk, and short- and long-term morbidity, adding to the
      "burden of therapy" in an increasing number of survivors. Thus, the need to
      reduce toxicity in pediatric ALL is becoming increasingly important. This work
      focuses on the risk factors, pathogenesis, clinical features, and emergency
      management of the life-threatening complications of ALL at presentation and
      during subsequent chemotherapy, including leucostasis, tumor lysis syndrome,
      infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential
      strategies to abrogate these toxicities in the future are also discussed.

PMID- 29222264
TI  - Incorporation of nonchemotherapeutic agents in pediatric acute lymphoblastic
      leukemia.
AB  - With current available therapies, the prognosis for most children and adolescents
      with acute lymphoblastic leukemia (ALL) is favorable. However, the multiagent
      chemotherapy regimens used to treat newly diagnosed patients are associated with
      many acute and long-term complications, and therapy for relapsed disease is
      intensive and suboptimally effective. Over the last decade, several
      nonchemotherapeutic approaches have been evaluated, with the goal of identifying
      more effective, less toxic therapies that can be used in conjunction with, or
      even replace, current regimens. Novel nonchemotherapeutic therapies with activity
      in ALL include (1) tyrosine kinase inhibitors in high-risk patient subsets in
      whom potentially targetable alterations have been identified and (2)
      immunotherapeutic approaches, such as monoclonal antibodies, immunotoxins,
      bispecific T-cell-engaging antibodies, and chimeric antigen receptor T cells.
      This review summarizes promising results from recent clinical trials of these
      novel treatments.

PMID- 29222265
TI  - Iron overload in thalassemia: different organs at different rates.
AB  - Thalassemic disorders lie on a phenotypic spectrum of clinical severity that
      depends on the severity of the globin gene mutation and coinheritance of other
      genetic determinants. Iron overload is associated with increased morbidity in
      both patients with transfusion-dependent thalassemia (TDT) and non-transfusion
      dependent thalassemia (NTDT). The predominant mechanisms driving the process of
      iron loading include increased iron burden secondary to transfusion therapy in
      TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis
      and hepcidin suppression in NTDT. Different organs are affected differently by
      iron overload in TDT and NTDT owing to the underlying iron loading mechanism and
      rate of iron accumulation. Serum ferritin measurement and noninvasive imaging
      techniques are available to diagnose iron overload, quantify its extent in
      different organs, and monitor clinical response to therapy. This chapter
      discusses the general approach to iron chelation therapy based on organ
      involvement using the available iron chelators: deferoxamine, deferiprone, and
      deferasirox. Other novel experimental options for treatment and prevention of
      complications associated with iron overload in thalassemia are briefly discussed.

PMID- 29222266
TI  - Impact of bone disease and pain in thalassemia.
AB  - Conventional treatment of thalassemia, namely regular blood transfusion and iron
      chelation, improves perspectives and quality of life; however, successful
      treatment leads to more time in which long-term complications such as bone
      disease can develop. Thalassemia bone disease (TBD) is unique: all aspects, from
      bone anatomy and bone quality to mineral density, may be affected, with important
      morbidity including osteoporosis, fractures, spinal deformities, nerve
      compression, and pain. Clinical presentations include growth impairment, rickets
      like features, back pain, spinal deformities, any sign of nerve compression,
      severe osteoporosis, and fragility fractures. Age, history, physical examination,
      and diagnostic tests support orientation on risk factors. These include bone
      marrow expansion, toxicity from iron overload and iron chelation, endocrine
      dysfunctions (hypogonadism, hypohyperparathyroidism, hypothyroidism, growth
      hormone deficiency, diabetes), and vitamin (D, C, K) and zinc deficiencies.
      Several of these may coexist in an individual for a long time and at different
      degrees, making clarification of the relative contribution and selection of the
      best therapeutic options a challenge. Milestones for prevention of TBD are early
      and full inhibition of bone marrow hyperplasia and iron toxicity. Empowering
      patients' positive resources is key for achieving long-term healthy habits with
      regard to diet, physical activity, sunlight exposure, and lifestyle. Pain,
      related or unrelated to bone disease, is frequent in thalassemia. The most
      important targets for the hematologist include having an expert orientation on
      disease-related causes of pain, driving differential diagnosis, providing
      effective pain relief and, where feasible, removing the cause.

PMID- 29222267
TI  - New therapeutic targets in transfusion-dependent and -independent thalassemia.
AB  - beta-Thalassemias are characterized by reduced production of beta-globin chain,
      resulting in alpha/beta-chain unbalance and precipitation of alpha-globin-heme
      complexes and determining ineffective erythropoiesis. Ineffective erythropoiesis,
      chronic hemolytic anemia, and compensatory hematopoietic expansion are the
      disease hallmarks, and they are related to the severity of the chain unbalance.
      Several clinical forms of beta-thalassemia, including the coinheritance of beta
      thalassemia with hemoglobin E resulting in hemoglobin E/beta-thalassemia, have
      been described. Clinically, beta-thalassemias can be classified as transfusion
      dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT)
      according to the severity of the phenotype, which is caused by a wide spectrum of
      mutations in a homozygous or compound heterozygous state. Current treatment of
      TDT consists of regular transfusions that lead to iron overload, requiring iron
      chelation to prevent iron-related organ toxicity. NTDT patients do not require
      transfusions or only occasionally require them; however, they develop iron
      overload as well because of increased intestinal iron absorption caused by
      chronic anemia. Hematopoietic stem cell allogenic transplant is the only approved
      cure for beta-thalassemia; however, it is still limited by clinical conditions
      and the availability of matched donors as well as by potential graft-versus-host
      disease (GVHD). Gene therapy could avoid the GVHD risk, although hematopoietic
      stem cells must be genetically modified ex vivo. Epigenetic manipulation and
      genomic editing are novel experimental approaches. An increased understanding of
      the pathophysiology that controls the disease process prompted us to explore
      alternative therapeutic approaches that address the underlying chain unbalance,
      ineffective erythropoiesis, and iron dysregulation. Molecules, such as JAK2
      inhibitors and the activin-receptor ligand trap that target ineffective
      erythropoiesis, are already in clinical trials with promising results. Other
      agents aimed to generate iron-restricted erythropoiesis are also under
      experimental evaluation.

PMID- 29222269
TI  - Current treatment of double hit and double expressor lymphoma.
AB  - A 60-year-old female presented with abdominal pain and distension. Following
      computed tomography scans of the abdomen and pelvis, she was taken urgently to
      the operating room, with the belief that she had appendicitis with perforation.
      At laparotomy, the findings were consistent with an ovarian carcinoma; there was
      extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive
      surgery was performed including total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. The final pathology, however, revealed infiltration with
      medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6
      by immunohistochemistry. MYC and BCL2 translocations were identified by
      fluorescence in situ hybridization consistent with a diagnosis of high-grade B
      cell lymphoma with rearrangements of MYC and BCL2 With the current data
      available, what is the optimal treatment of this patient?

PMID- 29222268
TI  - Tailoring front-line therapy in diffuse large B-cell lymphoma: who should we
      treat differently?
AB  - Although there have been significant insights into the biology of diffuse large B
      cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has
      been disappointing over the same timeframe. This is not for want of trying. In
      2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisone) remains the "gold standard," despite all of our insights into cell-of
      origin and other subgroups. We have traditionally used clinical risk factors to
      tailor our therapies and have tested intensification of chemotherapy with little
      success. We are now in an era of testing therapies according to the molecular
      phenotype of the individual's tumor. Many phase 1/2 studies have looked at adding
      targeted agents to conventional R-CHOP with some promise. The phase 3 data are
      now starting to emerge. Are we ready yet to modify our standard of care and have
      we reached an era of precision medicine in DLBCL? The answer to this is "not
      yet." The exception is perhaps patients with the newly defined World Health
      Organization category of high-grade B-cell lymphoma with rearrangements of MYC
      and BCL2 and/or BCL6, the so-called double- and triple-hit lymphomas. In these
      tumors there has been a move away from R-CHOP to more intensified regimens,
      however, has not been based upon rigorous prospective evaluation but review of
      retrospective datasets. This article will review the molecular subgroups of
      DLBCL, interventional strategies, and the outcomes of these interventions to
      date.

PMID- 29222270
TI  - Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies.
AB  - Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct
      clinicopathologic entity that predominantly affects adolescents and young adults
      and is more common in female subjects. Although PMBCL is considered to be a
      subtype of diffuse large B-cell lymphoma, its clinical, morphologic, and
      biological characteristics overlap significantly with those of nodular sclerosing
      Hodgkin lymphoma (NSHL). Over the past few years, the shared biology of these 2
      entities has been highlighted in several studies, and mediastinal gray zone
      lymphoma, with features intermediate between PMBCL and NSHL, has been recognized
      as a unique molecular entity. Although there is a lack of consensus about the
      optimal therapeutic strategy for adolescent and young adult patients newly
      diagnosed with PMCBL, highly curative strategies that obviate the need for
      mediastinal radiation are favored by most. Progress in understanding the biology
      of PMBCL and its close relationship to NSHL have helped pave the way for the
      investigation of novel approaches such as immune checkpoint inhibition. Other
      strategies such as adoptive T-cell therapy and targeting CD30 are also being
      studied.

PMID- 29222271
TI  - Optimizing therapy for mantle cell lymphoma.
AB  - Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and
      benefit from early initiation of rituximab and high-dose cytarabine- or
      bendamustine-based therapies. Some patients, however, present with primarily
      nonnodal disease that can follow either an indolent or a rapidly progressive,
      treatment-resistant clinical course. Rarely, patients present with explosive
      disease that can be challenging to manage and often involves the central nervous
      system. New agents with improved therapeutic indices facilitate treatment while
      maintaining quality of life, but also present new complications at the time of
      treatment failure. Although uncommon presentations are not new to clinicians who
      treat MCL, the increasing clarity of underlying biology and prognostic
      implications may help us develop more specialized treatment strategies.

PMID- 29222272
TI  - Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.
AB  - Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which
      rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an
      extensive but ineffective inflammatory/immune cell infiltrate. This striking
      feature suggests that malignant HRS cells escape immunosurveillance and interact
      with immune cells in the cancer microenvironment for survival and growth. We
      previously found that cHLs have a genetic basis for immune evasion: near-uniform
      copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci,
      CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of
      these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1
      receptor-positive immune effectors in the tumor microenvironment and induce PD-1
      signaling and associated immune evasion. The genetic bases of enhanced PD-1
      signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

PMID- 29222273
TI  - Emerging role of novel therapies in Hodgkin lymphoma: proceed with caution.
AB  - Based on very high response rates in the relapsed and refractory setting,
      brentuximab vedotin and the programmed cell death protein 1 (PD-1) inhibitors,
      nivolumab and pembrolizumab, have quickly been incorporated into clinical trials
      for first- and second-line therapy of Hodgkin lymphoma. Preliminary data show
      that brentuximab vedotin alone is not adequate therapy for newly diagnosed
      Hodgkin lymphoma in older patients, but modestly decreases the risk of relapse
      when combined with adriamycin, vinblastine, and dacarbazine in patients with
      previously untreated advanced-stage disease. In second-line therapy, combining
      brentuximab vedotin with conventional chemotherapy or with PD-1 inhibitors as
      pretransplant salvage is associated with high overall and complete response
      rates, although further follow up is needed to assess whether posttransplant
      outcomes are improved. Although these new drugs are well tolerated when given as
      single agents, unexpected toxicities have been encountered with combination
      regimens, specifically severe pulmonary toxicity with the bleomycin and
      brentuximab vedotin combination and frequent infusion-related reactions. There is
      concern with the use of PD-1 inhibitors as first-line therapy due to the
      theoretical potential for more frequent or severe immune-mediated toxicities in
      patients who have not received prior chemotherapy. Aside from these concerns,
      these new agents have the potential to improve outcomes for patients even
      further, bringing us closer to eradicating recurrent Hodgkin lymphoma.

PMID- 29222274
TI  - Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving
      unique management.
AB  - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity
      with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes
      of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological
      and clinical features. Histologically, the disease-defining lymphocyte
      predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL
      mostly has a rather indolent course, and patients usually are diagnosed in early
      stages. The prognosis of early-stage NLPHL is excellent, with progression-free
      survival and overall survival rates exceeding 90% after involved-field
      radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting
      of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin,
      vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than
      stage IA). In contrast, patients with advanced disease at diagnosis tend to
      relapse either with NLPHL histology or with histological transformation into
      aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line
      treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL
      patients with multiple relapses successfully respond to salvage therapy in many
      cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to
      high-dose chemotherapy followed by autologous stem cell transplantation.
      Treatment at disease recurrence should be chosen on the basis of various factors,
      including histology at relapse, time to relapse, extent of disease at relapse,
      and prior treatment. Because death among NLPHL patients is more often caused by
      therapy-related late effects than lymphoma-related complications, optimizing the
      risk-benefit ratio of treatment by decreasing toxicity whenever possible is the
      major goal of clinical research in this disease.

PMID- 29222275
TI  - The mutational landscape of chronic lymphocytic leukemia and its impact on
      prognosis and treatment.
AB  - The typical genome of chronic lymphocytic leukemia (CLL) carries ~2000 molecular
      lesions. Few mutations recur across patients at a frequency >5%, whereas a large
      number of biologically and clinically uncharacterized genes are mutated at lower
      frequency. Approximately 80% of CLL patients carry at least 1 of 4 common
      chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion
      17p12, and trisomy 12. Knowledge of the CLL genome has translated into the
      availability of molecular biomarkers for prognosis and treatment prediction.
      Prognostic biomarkers do not affect treatment choice, and can be integrated into
      prognostic scores that are based on both clinical and biological variables.
      Molecular predictive biomarkers affect treatment choice, and currently include
      TP53 disruption by mutation and/or deletion and IGHV mutation status. TP53
      disruption by gene mutation and/or deletion associates with chemoimmunotherapy
      failure and mandates treatment with innovative drugs, including ibrutinib,
      idelalisib, or venetoclax. The mutation status of IGHV genes represents a
      predictive biomarker for identifying patients that may benefit the most from
      chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. Assessment
      of these biomarkers at the time of treatment requirement is recommended by most
      current guidelines for CLL management. Other molecular predictors are under
      investigation, but their application in clinical practice is premature.

PMID- 29222276
TI  - Optimizing frontline therapy of CLL based on clinical and biological factors.
AB  - The heterogeneity of the clinical course of chronic lymphocytic leukemia (CLL)
      ranges from an indolent course, where patients do not require therapy for many
      years, to a very aggressive disease, where treatment is required soon after
      diagnosis and relapses may occur early. The improved tools for prognostication
      allow predicting the outcome of patients with increasing reliability. Some
      markers also allow selecting more specific therapies with improved activity in
      the presence of certain genetic or clinical features of CLL. Of these markers,
      TP53 dysfunction, age, the presence of comorbidities and the immunoglobulin heavy
      chain variable region gene mutational status, or serum markers such as beta2
      microglobulin have shown independent prognostic value in multiple prospective
      trials. During the last 10 years, multiple novel agents have become available.
      The advent of oral kinase inhibitors or Bcl-2 antagonists has provided highly
      effective options with acceptable toxicity. This manuscript summarizes the
      current evidence of the available treatment options and proposes an integrated
      algorithm for the frontline therapy of CLL.

PMID- 29222277
TI  - How should we sequence and combine novel therapies in CLL?
AB  - With the recent approval of several effective and well-tolerated novel agents
      (NAs), including ibrutinib, idelalisib, venetoclax, and obinutuzumab, patients
      with chronic lymphocytic leukemia (CLL) have more therapeutic options than ever
      before. The availability of these agents is both an important advance for
      patients but also a challenge for practicing hematologist/oncologists to learn
      how best to sequence NAs, both with respect to chemoimmunotherapy (CIT) and to
      other NAs. The sequencing of NAs in clinical practice should be guided both by an
      individual patient's prognostic markers, such as FISH and immunoglobulin heavy
      chain variable region (IGHV)-mutation status, as well as the patient's medical
      comorbidities and goals of care. For older, frailer patients with lower-risk CLL
      prognostic markers, NA monotherapy may remain a mainstay of CLL treatment for
      years to come. For younger, fitter patients and those with higher-risk CLL, such
      as del(17p) or unmutated IGHV, combination approaches may prove to be more
      valuable than NA monotherapy. Trials are currently evaluating the efficacy of
      several such combination approaches, including NA plus anti-CD20 monoclonal
      antibody, NA plus NA (with or without anti-CD20 monoclonal antibody), and NA plus
      CIT. Given the tremendous efficacy of the already approved NAs, as well as the
      promising data for next generation NAs, the development of well-tolerated, highly
      effective combination strategies with curative potential for patients with CLL
      has become a realistic goal.

PMID- 29222278
TI  - Safety profiles of novel agent therapies in CLL.
AB  - A 70-year-old man with relapsed/refractory chronic lymphocytic leukemia has
      multiple comorbidities including atrial fibrillation (on warfarin for
      anticoagulation), irritable bowel syndrome, and chronic renal insufficiency. Two
      years ago, he received bendamustine and rituximab as first-line therapy for
      chronic lymphocytic leukemia and achieved partial response, but now has relapsed.
      Fluorescence in situ hybridization cytogenetics reveals deletion 17p. Which novel
      agent would you recommend for this patient?

PMID- 29222279
TI  - Follicular lymphoma: are we ready for a risk-adapted approach?
AB  - Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the
      Western hemisphere. The natural history of FL appears to have been favorably
      impacted by the introduction of rituximab after randomized clinical trials
      demonstrated that the addition of rituximab to standard chemotherapy induction
      has improved the overall survival. Yet, the disease is biologically and
      clinically heterogeneous with wide variations in outcomes for individual
      patients. The ability to accurately risk-stratify patients and then tailor
      therapy to the individual is an area of ongoing research. Historically, tumor
      grade, tumor burden, and the FL international prognostic index (version 1 and
      version 2) have been used to distinguish low-risk from high-risk patients.
      Biologic factors such as mutations in key genes can identify patients at high
      risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2,
      ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma
      International Prognostic Index). More recently, the quality of the response to
      initial therapy, as measured by either PET imaging or by remission duration, has
      been show to identify individuals at high risk. However, several unmet needs
      remain, including a better ability to identify high-risk patients at diagnosis,
      the development of predictive biomarkers for targeted agents, and strategies to
      reduce the risk of transformation.

PMID- 29222280
TI  - Toward personalized treatment in Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a rare lymphoma with 1000 to 1500 new
      patients diagnosed per year in the United States. Patients with WM can experience
      prolonged survival times, which seem to have increased in the last decade, but
      relapse is inevitable. The identification of recurrent mutations in the MYD88 and
      CXCR4 genes has opened avenues of research to better understand and treat
      patients with WM. These developments are giving way to personalized treatment
      approaches for these patients, focusing on increasing depth and duration of
      response alongside lower toxicity rates. In the present document, we review the
      diagnostic differential, the clinical manifestations, and the pathological and
      genomic features of patients with WM. We also discuss the safety and efficacy
      data of alkylating agents, proteasome inhibitors, monoclonal antibodies, and
      Bruton tyrosine kinase inhibitors in patients with WM. Finally, we propose a
      genomically driven algorithm for the treatment of WM. The future of therapies for
      WM appears bright and hopeful, but we should be mindful of the cost-effectiveness
      and long-term toxicity of novel agents.

PMID- 29222281
TI  - Improved biological insight and influence on management in indolent lymphoma.
      Talk 3: update on nodal and splenic marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL) are
      rare indolent chronic B-cell lymphomas. Prognosis is typically good with median
      survival around 10-15 years. Management is generally based on the presence of
      symptoms or high tumor burden. There are no standard treatments for these 2
      entities, and therapeutic strategies are rapidly evolving. Clinical developments
      for these 2 entities are oriented by genomic studies, with largely overlapping
      mutational profiles involving the NOTCH, B-cell receptor (BcR) and nuclear factor
      kappaB (NF-kappaB) signaling, chromatin remodeling, and the cytoskeleton.
      Although new therapeutic options based on targeting signaling pathways and
      overcoming resistance are increasingly available, few specific prospective
      studies are performed for these rare subtypes, limiting the conclusions that can
      be drawn. Novel drugs targeting B-cell signaling have shown promise, including
      ibrutinib and copanlisib. The second-generation oral immunomodalator (IMiD)
      lenalidomide showed impressive results when combined with rituximab. Other
      potential solutions include targeting the NF-kappaB, JAK/STAT, BCL2, NOTCH, and
      Toll-like receptor signaling pathways; however, studies in these 2 MZL entities
      are yet to prove a definitive benefit. Molecular profiling is now a cornerstone
      of diagnostic, prognostic, and therapeutic strategies to offer patient- and
      disease-specific solutions. The development of a wider range of effective
      targeted therapies and prognostic biomarkers is keenly awaited and is expected to
      strongly affect the natural history of SMZL and NMZL.

PMID- 29222282
TI  - Advances in the diagnosis and treatment of Von Willebrand disease.
AB  - Von Willebrand disease (VWD) is the most common inherited bleeding disorder, yet
      diagnosis and management remain challenging. Development and use of bleeding
      assessment tools allows for improved stratification of which patients may require
      further assessment and which patients are most likely to require treatment of
      their VWD. New options for laboratory assessment of von Willebrand factor (VWF)
      activity include a new platelet-binding assay, the VWF:GPIbM, which is subject to
      less variability than the ristocetin cofactor activity assay, and collagen
      binding assays that provide insight into a different function of VWF. Genetic
      testing may be helpful in some cases where a type 2 VWD variant is suspected but
      is usually not helpful in type 1 VWD. Finally, treatment options for VWD are
      reviewed, including the use of recombinant VWF. Despite these advances, still
      more work is required to improve diagnosis, treatment, and quality of life for
      affected patients.

PMID- 29222283
TI  - Hereditary thrombocytopenias: a growing list of disorders.
AB  - The introduction of high throughput sequencing (HTS) techniques greatly improved
      the knowledge of inherited thrombocytopenias (ITs) over the last few years. A
      total of 33 different forms caused by molecular defects affecting at least 32
      genes have been identified; along with the discovery of new disease-causing
      genes, pathogenetic mechanisms of thrombocytopenia have been better elucidated.
      Although the clinical picture of ITs is heterogeneous, bleeding has been long
      considered the major clinical problem for patients with IT. Conversely, the
      current scenario indicates that patients with some of the most common ITs are at
      risk of developing additional disorders more dangerous than thrombocytopenia
      itself during life. In particular, MYH9 mutations result in congenital
      macrothrombocytopenia and predispose to kidney failure, hearing loss, and
      cataracts, MPL and MECOM mutations cause congenital thrombocytopenia evolving
      into bone marrow failure, whereas thrombocytopenias caused by RUNX1, ANKRD26, and
      ETV6 mutations are characterized by predisposition to hematological malignancies.
      Making a definite diagnosis of these forms is crucial to provide patients with
      the most appropriate treatment, follow-up, and counseling. In this review, the
      ITs known to date are discussed, with specific attention focused on clinical
      presentations and diagnostic criteria for ITs predisposing to additional
      illnesses. The currently available therapeutic options for the different forms of
      IT are illustrated.

PMID- 29222284
TI  - Management of newly diagnosed immune thrombocytopenia: can we change outcomes?
AB  - Immune thrombocytopenia resulting from antibody-mediated platelet destruction
      combined with impaired platelet production is a common cause of thrombocytopenia.
      The decision to treat newly diagnosed patients is based on several factors
      including ceasing hemorrhagic manifestations, increasing the platelet count,
      prevention of bleeding, and inducing remission. Current standard first-line
      therapy is a course of corticosteroids. Although this treatment paradigm
      increases the platelet count in the majority of patients, a high percentage
      relapse after discontinuation of corticosteroid therapy. For this reason,
      intensification of first-line therapy that results in superior long-term
      remission rates would be desirable. This manuscript focuses primarily on adults
      with idiopathic thrombocytopenic purpura (ITP), highlighting pediatric data and
      practice when applicable. The primary aim is to outline upfront strategies for
      treatment-naive patients with ITP to enhance remission rates, taking into account
      assessment of the risks and benefits of these approaches.

PMID- 29222285
TI  - Five lessons learned about long-term pain management in adults with sickle cell
      disease.
AB  - Chronic pain affects one-half of adults with sickle cell disease (SCD). Despite
      the prevalence of chronic pain, few studies have been performed to determine the
      best practices for this patient population. Although the pathophysiology of
      chronic pain in SCD may be different from other chronic pain syndromes, many of
      the guidelines outlined in the pain literature and elsewhere are applicable; some
      were consensus-adopted in the 2014 National Heart, Lung, and Blood Institute SCD
      Guidelines. Recommended practices, such as controlled substance agreements and
      monitoring of urine, may seem unnecessary or counterproductive to hematologists.
      After all, SCD is a severe pain disorder with a clear indication for opioids, and
      mistrust is already a major issue. The problem, however, is not with a particular
      disease but with the medicines, leading many US states to pass broad legislation
      in attempts to curb opioid misuse. These regulations and other key tenets of
      chronic pain management are not meant to deprive adults with SCD of appropriate
      therapies, and their implementation into hematology clinics should not affect
      patient-provider relationships. They simply encourage prudent prescribing
      practices and discourage misuse, and should be seen as an opportunity to more
      effectively manage our patient's pain in the safest manner possible. In line with
      guideline recommendations as well as newer legislation, we present five lessons
      learned. These lessons form the basis for our model to manage chronic pain in
      adults with SCD.

PMID- 29222286
TI  - Improving Emergency Department-Based Care of Sickle Cell Pain.
AB  - Pain is the leading cause of emergency department (ED) visits for individuals
      living with sickle cell disease (SCD). The care that is delivered in the ED is
      often cited by patients with SCD as the area of health care in greatest need of
      improvement. In 2014, the National Heart, Lung, and Blood Institute released
      guidelines for the care of SCD, including recommendations for the management of
      acute sickle cell pain in the ED. These guidelines provide a framework to
      understand the elements of ideal emergency sickle cell pain care; however, they
      do not provide guidance on barriers and facilitators to achieving these ideals in
      the complex system of the ED. Presented in this article are 4 tenets of
      implementing guideline-adherent emergency sickle cell care gleaned from the
      available literature and continuous quality improvement efforts at our
      institution. These include: (1) strategies to reduce negative provider attitudes
      toward patients with SCD; (2) strategies to reduce time-to-first-dose of
      analgesic medication; (3) strategies to improve ED pain care beyond the first
      dose of medication; and (4) strategies to improve ED patient safety. Application
      of the principles discussed within can improve patient and provider satisfaction,
      quality, and safety.

PMID- 29222287
TI  - Rigorous and practical quality indicators in sickle cell disease care.
AB  - In recent years, several sickle cell-specific quality indicators have been
      developed using rigorous approaches. A review of the history and current status
      of the development of sickle cell-specific indicators highlights opportunities
      for future refinement. Despite efforts at alignment, lack of strong evidence
      hinders the adoption of current quality indicators across stakeholder groups.
      There are many directions in which to take the current existing quality
      indicators, including expanding to different age groups, aims of care such as
      safety and equity, and better understanding of contextual and environmental
      factors.

PMID- 29222289
TI  - What is the role of screening for pulmonary hypertension in adults and children
      with sickle cell disease?
AB  - Patient case: An 18-year-old male patient with homozygous hemoglobin SS disease
      was evaluated for progressive dyspnea and elevated tricuspid regurgitant jet
      velocity (TRV) on echocardiography. The patient's case is described in detail in
      Lancet1 He had been treated with regular transfusions since childhood for stroke,
      had rare episodes of vaso-occlusive pain episodes, and did not take narcotic pain
      medications. He presented with progressive severe dyspnea on exertion and lower
      extremity edema. His laboratory tests were notable for a total hemoglobin level
      of 11.8 g/dL and hemoglobin S levels <30% but with 18% reticulocytes and elevated
      markers of hemolysis, such as high plasma levels of lactate dehydrogenase,
      aspartate amino transferase, and indirect bilirubin. The computed tomography scan
      of his chest in Figure 1A-B shows a large pulmonary artery, which has a greater
      diameter than his aorta, and a mosaic perfusion pattern, typical for severe
      pulmonary arterial hypertension. His Doppler echocardiographic study (Figure 1C)
      showed an unusually high TRV of 5.93 m/s, consistent with a calculated pulmonary
      artery systolic pressure of >140 mm Hg (4 times the TRV squared = 4V2).
      Additional images in Figure 1D show a dilated right ventricle and right atrium
      with a compressed left ventricle. The patient's right heart catheterization
      revealed a pulmonary artery systolic pressure of 147 mm Hg and diastolic pressure
      of 49 mm Hg; note that the normal values are ~25/10 mm Hg.

PMID- 29222288
TI  - Cardiovascular complications in patients with sickle cell disease.
AB  - Sickle cell disease (SCD) is an autosomal recessive disease in which homozygosity
      for a single point mutation in the gene encoding the beta-globin chain produces
      hemoglobin S molecules that polymerize within the erythrocyte during
      deoxygenation; the result is sustained hemolytic anemia and vaso-occlusive
      events. As patients live to adulthood, the chronic impact of sustained hemolytic
      anemia and episodic vaso-occlusive episodes leads to progressive end-organ
      complications. This scenario culminates in the development of 1 or more major
      cardiovascular complications of SCD for which there are no approved or consensus
      therapies. These complications include elevated pulmonary artery systolic
      pressure, pulmonary hypertension, left ventricular diastolic heart disease,
      dysrhythmia, sudden death, and chronic kidney disease with associated
      proteinuria, microalbuminuria, and hemoglobinuria. In patients with advancing
      age, cardiopulmonary organ dysfunction and chronic kidney injury have significant
      effects on morbidity and premature mortality. Over the last 15 years, a number of
      tests have been validated in multiple replicate cohort studies that identify
      patients with SCD at the highest risk of experiencing pulmonary and systemic
      vasculopathy and death, providing for screening strategies tied to targeted, more
      aggressive diagnostic and therapeutic interventions.

PMID- 29222290
TI  - Chronic organ failure in adult sickle cell disease.
AB  - Sickle cell disease is now a chronic adult illness characterized by progressive
      multiorgan failure, particularly involving the brain and kidney. The etiology is
      multifactorial; it includes hemolysis and nitric oxide deficiency. As patients
      age, most experience neurologic insult. Twenty-five percent of older adults have
      had a clinical stroke and at least half of the population have had a silent
      infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with
      neuroimaging and neurocognitive testing is recommended. Identification and
      correction of modifiable risk factors such as nocturnal hypoxemia, obstructive
      sleep apnea, and physical exercise programs should be implemented. Patients with
      neurocognitive impairment require cognitive remediation and educational
      accommodations. Chronic renal disease occurs in 25% of older adults and results
      in 50% of their deaths. Renal failure often develops insidiously. It can be
      prevented or minimized by early screening and treatment of modifiable risk
      factors including hypertension and microalbuminuria. There is an increasing
      number of therapeutic options, including inhibitors of the renin angiotensin
      system, angiotensin-II receptor blockers, endothelin-1 receptor antagonist, and
      haptoglobin therapy. Patients with sickle cell disease have increased mortality
      rates from renal failure compared with nonsickle cell patients, in part from a
      lack of access to early multidisciplinary care, including timely initiation of
      dialysis and renal transplantation.

PMID- 29222291
TI  - Evolving treatment paradigms in sickle cell disease.
AB  - Sickle cell disease (SCD) is an inheritable hemoglobinopathy characterized by
      polymerization of hemoglobin S in red blood cells resulting in chronic hemolytic
      anemia, vaso-occlusive painful crisis, and multiorgan damage. In SCD, an
      increased reactive oxygen species (ROS) generation occurs both inside the red
      blood cells and inside the vascular lumen, which augment hemolysis and cellular
      adhesion. This review discusses the evolving body of literature on the role of
      ROS in the pathophysiology of SCD as well as some emerging therapeutic approaches
      to SCD with a focus on the reduction of ROS.

PMID- 29222292
TI  - Uncoding the genetic heterogeneity of myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease
      characterized by functional impairment of hematopoiesis and abnormal bone marrow
      morphology. The type and severity of hematopoietic dysfunction in MDS are highly
      variable, and the kinetics of disease progression are difficult to predict.
      Genomic studies have shown that MDS is typically driven by a multistep somatic
      genetic process affecting a core set of genes. By definition, recurrent MDS
      driver mutations all drive clonal dominance, although they can have stereotyped
      positions in the clonal hierarchy or patterns of comutation association and
      exclusivity. Furthermore, environmental context, such as exposures to cytotoxic
      chemotherapy or the presence of germ-line predisposition, can influence disease
      pathogenesis and clinical outcomes. This review will address how an enhanced
      understanding of MDS genetics may enable refinement of current diagnostic schema,
      improve understanding of the pathogenesis of therapy-related MDS, and identify
      germ-line predispositions to development of MDS that are more common than
      recognized by standard clinical evaluation.

PMID- 29222293
TI  - Current treatment algorithm for the management of lower-risk MDS.
AB  - Lower risk myelodysplastic syndromes (MDS), defined as MDS with a Revised
      International Prognostic Scoring System score <=3.5 points, will remain a
      challenging entity in 2018. Supportive care continues to be the linchpin of
      treatment, although the options to reduce transfusion needs are broadening. To
      achieve red blood cell transfusion independence in non-del(5q) patients,
      erythropoiesis-stimulating agents remain a mainstay of therapy as long as
      endogenous erythropoietin levels are <500 U/L (and preferably <200 U/L).
      Experimental strategies for patients ineligible for erythropoiesis-stimulating
      agents or relapsing after gaining transfusion independence include
      immunosuppressive agents, transforming growth factor beta inhibitors, and
      lenalidomide. All these alternatives have shown reasonable response rates in
      selected patient populations with lower risk MDS. Patients with del(5q) disease
      can derive long-term benefit from lenalidomide, and some patients remain
      transfusion free for extended periods even after discontinuation of the drug. In
      rare cases in which thrombocytopenia is the main clinical problem leading to
      clinically significant bleeding events, thrombopoietin receptor analogues may
      alleviate bleeding, increase platelet counts, and rarely lead to trilineage
      responses. It seems prudent to use these drugs only in patients with confirmed
      bone marrow blast counts <5%. Allogeneic stem cell transplantation is reasonable
      for patients with high molecular risk of progression and those failing several
      lines of treatment with signs of progression toward higher-risk MDS.

PMID- 29222294
TI  - Incorporating novel approaches in the management of MDS beyond conventional
      hypomethylating agents.
AB  - In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS)
      has revolved around the azanucleosides, azacitidine and decitabine, which at
      lower doses are postulated to work predominantly via their effects on inhibition
      of DNA methyltransferases and consequent DNA hypomethylation. For patients who
      relapse after, or do not respond to, hypomethylating agent therapy, the outcome
      is dismal, and new agents and approaches that have the potential to alter the
      natural history of these diseases are desperately needed. Allogeneic stem cell
      transplant is the only known potentially curative approach in MDS, but its
      applicability has been limited by the advanced age of patients and attendant
      comorbidities. There is now an increasing array of new agents under clinical
      investigation in MDS that aim to exploit our expanding understanding of molecular
      pathways that are important in the pathogenesis of MDS. This review focuses on a
      critical appraisal of novel agents being evaluated in higher-risk MDS that go
      beyond the conventional hypomethylating agent therapies approved by the US Food
      and Drug Administration.

PMID- 29222295
TI  - Myeloproliferative neoplasms: from origins to outcomes.
AB  - Substantial progress has been made in our understanding of the pathogenetic basis
      of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade
      ago heralded a new age for patient care as a consequence of improved diagnosis
      and the development of therapeutic JAK inhibitors. The more recent identification
      of mutations in calreticulin brought with it a sense of completeness, with most
      patients with myeloproliferative neoplasm now having a biological basis for their
      excessive myeloproliferation. We are also beginning to understand the processes
      that lead to acquisition of somatic mutations and the factors that influence
      subsequent clonal expansion and emergence of disease. Extended genomic profiling
      has established a multitude of additional acquired mutations, particularly
      prevalent in myelofibrosis, where their presence carries prognostic implications.
      A major goal is to integrate genetic, clinical, and laboratory features to
      identify patients who share disease biology and clinical outcome, such that
      therapies, both existing and novel, can be better targeted.

PMID- 29222296
TI  - What are the current treatment approaches for patients with polycythemia vera and
      essential thrombocythemia?
AB  - Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic
      myeloproliferative neoplasms that are characterized by thrombohemorrhagic
      complications, symptom burden, and impaired survival mainly due to thrombosis,
      progression to myelofibrosis, and transformation to acute leukemia. In this
      manuscript, we will review the most recent changes in diagnostic criteria, the
      improvements in risk stratification, and the "state of the art" in the daily
      management of these disorders. The role of conventional therapies and novel
      agents, interferon alpha and the JAK2 inhibitor ruxolitinib, is critically
      discussed based on the results of a few basic randomized clinical studies.
      Several unmet needs remain, above all, the lack of a curative approach that might
      overcome the still burdensome morbidity and mortality of these hematologic
      neoplasms, as well as the toxicities associated with therapeutic agents.

PMID- 29222297
TI  - Current treatment algorithm for the management of patients with myelofibrosis,
      JAK inhibitors, and beyond.
AB  - Myelofibrosis (MF) is a heterogeneous disorder characterized by splenomegaly,
      constitutional symptoms, ineffective hematopoiesis, and an inherent risk of
      leukemic transformation. The past decade has seen a massive shift in available
      therapeutic options for our patients and we are learning how and when to use
      novel agents, either alone or in combination, during the disease course. This has
      translated into improved management of splenomegaly, significant amelioration in
      disease-related symptom burden for many, and may lead to improved survival. But
      limitations in the therapeutic options remain. Moreover, enhanced delineation of
      the mutational landscape of MF has offered both increasingly complex prognostic
      algorithms and yielded further potential therapeutic avenues. In this review, we
      will focus on stratifying both standard and experimental therapeutic management
      in 2017 and 2018 and postulate on the emerging treatments that will likely become
      part of our increasingly complex treatment algorithm.

PMID- 29222298
TI  - Management of multiple myeloma in the newly diagnosed patient.
AB  - Multiple myeloma is the second most frequent hematological disease. The
      introduction of melphalan as high-dose therapy followed by autologous
      hematopoietic cell transplantation (HDT/ASCT) for young patients and the
      availability of novel agents for young and elderly patients with multiple myeloma
      have dramatically changed the perspective of treatment. However, further research
      is necessary if we want definitively to cure the disease. Treatment goals for
      transplant-eligible and non-transplant-eligible patients should be to prolong
      survival by achieving the best possible response while ensuring quality of life.
      For young patients, HDT-ASCT is a standard of care for treatment, and its
      efficacy has been enhanced and challenged by the new drugs. For elderly patients,
      treatment options were once limited to alkylators, but new upfront treatment
      combinations based on novel agents (proteasome inhibitors and immunomodulatory
      drugs) combined or not with alkylators have significantly improved outcomes.
      Extended treatment of young and elderly patients improves the quality and
      duration of clinical responses; however, the optimal scheme, appropriate doses,
      and duration of long-term therapy have not yet been fully determined. This review
      summarizes progress in the treatment of patients with newly diagnosed multiple
      myeloma, addressing critical questions such as the optimal induction, early vs
      late ASCT, consolidation and/or maintenance for young patients, and how we can
      choose the best treatment option for non-transplant-eligible patients.

PMID- 29222299
TI  - Management of multiple myeloma in the relapsed/refractory patient.
AB  - The approach to the patient with relapsed or relapsed/refractory multiple myeloma
      requires a careful evaluation of the results of previous treatments, the
      toxicities associated with it, and an assessment of prognostic factors. The
      majority of patients will have received prior therapy with drug combinations,
      including a proteasome inhibitor and an immune-modulatory agent. It is the
      physician's task to choose the right moment for the start of therapy and decide
      with the patient which goals need to be achieved. The choice of regimen is
      usually based on prior response, drugs already received, adverse effects,
      comorbidities of the patient, and expected efficacy and tolerability. Many double
      and triple drug combinations are available. In addition, promising new drugs such
      as pomalidomide, carfilzomib, and monoclonal antibodies are or will be available
      shortly, and other options can be explored in clinical trials. Finally,
      supportive care and palliative options need to be considered in later relapsed
      disease. Increasingly, it becomes important to consider the therapeutic options
      for the whole duration of the disease and integrate a systematic approach for the
      patient.

PMID- 29222300
TI  - Emerging options in multiple myeloma: targeted, immune, and epigenetic therapies.
AB  - Considerable progress has been made in the treatment of multiple myeloma in the
      past decade with median survival for the disease improving significantly. This
      has come through a combination of better understanding of the disease biology and
      coordinated research into new treatment approaches including better supportive
      care. However, patients eventually become refractory to available treatments and
      succumb to the disease, highlighting the need to develop new treatment
      approaches. The genetic heterogeneity in the disease and clonal evolution under
      treatment pressure underlie the development of resistance, underscoring the need
      to develop more effective therapies that can eradicate the disease at initial
      treatment as well as the need for new classes of drugs with varying mechanisms of
      action. To this end, there has been intense focus on exploring novel approaches
      to therapy including small-molecule inhibitors targeting specific abnormalities,
      immune therapies including monoclonal antibodies and adaptive T-cell therapy, as
      well as epigenetic approaches. Although many of these drugs are in the early
      stages of clinical development, the early data appear to be very promising. Many
      of these drugs can be safely and effectively combined with the current treatment
      classes such as proteasome inhibitors and immunomodulatory drugs, further
      enhancing the treatment options for myeloma.

PMID- 29222301
TI  - Optimizing the care model for an uncomplicated acute pain episode in sickle cell
      disease.
AB  - The pathophysiology, clinical presentation, and natural history of acute pain in
      sickle cell disease are unique and require a disease-centered approach that also
      applies general principles of acute and chronic pain management. The majority of
      acute pain episodes are managed at home without the need to access health care.
      The long-term consequences of poorly treated acute pain include chronic pain,
      adverse effects of chronic opioid usage, psychological maladjustment, poor
      quality of life, and excessive health care utilization. There is no standard
      protocol for management of an acute pain crisis in either the hospital or the
      community. The assumptions that severe acute pain must be managed in the hospital
      with parenteral opioids and that strong opioids are needed for home management of
      pain need to be questioned. Pain management in the emergency department often
      does not meet acceptable standards, while chronic use of strong opioids is likely
      to result in opioid-induced hyperalgesia, exacerbation of chronic pain symptoms,
      and opioid dependency. We suggest that an integrated approach is needed to
      control the underlying condition, modify psychological responses, optimize social
      support, and ensure that health care services provide safe, effective, and prompt
      treatment of acute pain and appropriate management of chronic pain. This
      integrated approach should begin at an early age and continue through the
      adolescent, transition, and adult phases of the care model.

PMID- 29222302
TI  - Pain-measurement tools in sickle cell disease: where are we now?
AB  - Pain is a complex multidimensional experience and the most common morbidity in
      patients with sickle cell disease (SCD). Tools to assess pain can be of use not
      only to guide pain treatment but also to provide insight into underlying pain
      neurobiology. Mechanisms of pain in SCD are multifactorial and are not completely
      elucidated. Although vaso-occlusion of microcirculation by sickled red cells is
      believed to be the underlying mechanism of acute vaso-occlusive pain, mechanisms
      for chronic pain and the transition from acute to chronic pain are under
      investigation. A number of modalities can be used in clinical practice and/or
      research to capture various dimensions of pain. Selection of a pain-assessment
      tool should be directed by the purpose of the assessment. Pain-assessment tools,
      many of which are currently in the early stages of validation, are discussed
      here. Development and validation of these multimodal tools is crucial for
      developing improved understanding of SCD pain and its management.

PMID- 29222303
TI  - Responsiveness of Patient-Reported Outcome Measurement Information System
      (PROMIS) pain domains and disease-specific patient-reported outcome measures in
      children and adults with sickle cell disease.
AB  - Case 1: A 33-year-old man with hemoglobin SS (homozygous hemoglobin S) disease
      presents for his regular clinic visit. He had 6 hospital admissions for pain over
      the past year. He also has avascular necrosis of the right hip. He takes daily
      hydroxyurea with hematologic changes indicative of compliance. He also takes
      morphine sustained release twice daily and morphine immediate release every 6
      hours as needed for pain. He feels that more optimal pain control at home would
      help him reduce his number of hospital admissions in the upcoming year and
      improve his daily functioning at home. His hematologist decides to use Patient
      Reported Outcome Measurement Information System (PROMIS) and Adult Sickle Cell
      Quality of Life Measurement Information System (ASCQ-ME) to follow changes in the
      patient's pain. Case 2: An 11-year-old girl with hemoglobin SS disease presents
      with her mother for her regular clinic visit. She had 2 admissions for pain over
      the past year. Her mother is concerned because she has been participating less in
      activities she previously enjoyed and missing classes to go to the school nurse
      because of pain. She is currently taking hydroxyurea and uses ibuprofen for pain.
      Her doctor prescribes morphine for home use but wants a way to measure if it is
      effective in improving her pain. Thus, her physician decides to use PROMIS and
      the Pediatric Quality of Life Inventory SCD (PedsQL SCD) module to determine the
      effectiveness of her pain control.

PMID- 29222304
TI  - Targeting novel mechanisms of pain in sickle cell disease.
AB  - Patients with sickle cell disease (SCD) suffer from intense pain that can start
      during infancy and increase in severity throughout life, leading to
      hospitalization and poor quality of life. A unique feature of SCD is vaso
      occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable
      episodes of acute pain. Microvascular obstruction during a VOC leads to impaired
      oxygen supply to the periphery and ischemia reperfusion injury, inflammation,
      oxidative stress, and endothelial dysfunction, all of which may perpetuate a
      noxious microenvironment leading to pain. In addition to episodic acute pain,
      patients with SCD also report chronic pain. Current treatment of moderate to
      severe pain in SCD is mostly reliant upon opioids; however, long-term use of
      opioids is associated with multiple side effects. This review presents up-to-date
      developments in our understanding of the pathobiology of pain in SCD. To help
      focus future research efforts, major gaps in knowledge are identified regarding
      how sickle pathobiology evokes pain, pathways specific to chronic and acute
      sickle pain, perception-based targets of "top-down" mechanisms originating from
      the brain and neuromodulation, and how pain affects the sickle microenvironment
      and pathophysiology. This review also describes mechanism-based targets that may
      help develop novel therapeutic and/or preventive strategies to ameliorate pain in
      SCD.

PMID- 29222305
TI  - Biology of CNS lymphoma and the potential of novel agents.
AB  - Primary and secondary CNS lymphomas are aggressive brain tumors that pose an
      immense challenge to define in terms of molecular pathogenesis, as well as to
      effectively treat. During the past 10 years improvements in survival have been
      achieved with the implementation of anti-CD20 immunotherapy and optimization of
      dose-intensive consolidation strategies. The applications of whole-exome
      sequencing, comparative genomic hybridization, transcriptional profiling, and
      examination of the tumor microenvironment, particularly in the context of
      clinical investigation, provide insights that create a roadmap for the
      development and implementation of novel targeted agents for this disease. A body
      of genetic evidence strongly suggested that primary CNS lymphomas (PCNSLs) are
      likely largely dependent on NF-kappaB prosurvival signals, with enrichment of
      mutations involving the B-cell receptor pathway, in particular myeloid
      differentiation primary response 88 and cluster of differentiation 79B. The first
      set of early-phase investigations that target NF-kappaB in PCNSL have now been
      completed and support the NF-kappaB hypothesis but at the same time reveal that
      much work needs to be done to translate these results into meaningful advances in
      survival for a large fraction of patients. Insights into secondary prosurvival
      pathways that mediate drug resistance is a priority for investigation. Similarly,
      further evaluation of the immune-suppressive mechanisms in the CNS lymphoma tumor
      microenvironment is requisite for progress. Combinatorial interventions that
      promote the antitumor immune response have significant potential. With increasing
      availability of targeted agents, there is also a need to develop more sensitive
      imaging tools, not only to detect this highly invasive brain neoplasm but also
      potentially to define an evolving molecular phenotype to facilitate precision
      medicine.

PMID- 29222306
TI  - Therapy of primary CNS lymphoma: role of intensity, radiation, and novel agents.
AB  - Primary central nervous system (CNS) lymphomas represent a subgroup of
      malignancies with specific characteristics, an aggressive course, and
      unsatisfactory outcome in contrast with other lymphomas comparable for tumor
      burden and histological type. Despite the high sensitivity to conventional
      chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment
      efficacy is limited by several factors, including the biology and
      microenvironment of this malignancy and the "protective" effect of the blood
      brain barrier, which limits the access of most drugs to the CNS. Patients who
      survive are at high risk of developing treatment-related toxicity, mainly
      disabling neurotoxicity, raising the question of how to balance therapy
      intensification with the control of side effects. Recent therapeutic progress and
      effective international cooperation have resulted in a significantly improved
      outcome over the past 2 decades, with a higher proportion of patients receiving
      treatment with curative intent. Actual front-line therapy consists of high-dose
      methotrexate-based polychemotherapy. Evidence supporting the addition of an
      alkylating agent and rituximab is growing, and a recent randomized trial
      demonstrated that the combination of methotrexate, cytarabine, thiotepa, and
      rituximab (MATRix regimen) is associated with a significantly better overall
      survival. Whole-brain irradiation and high-dose chemotherapy supported by
      autologous stem cell transplantation are 2 effective consolidation strategies in
      patients with a disease responsive to induction chemotherapy. Different
      strategies such as alkylating maintenance, conservative radiotherapy, and
      nonmyeloablative consolidation are being addressed in large randomized trials and
      a more accurate knowledge of the molecular and biological characteristics of this
      malignancy are leading to the development of target therapies in
      refractory/relapsing patients, with the overall aim to incorporate new active
      agents as part of first-line treatment. The pros and cons of these approaches
      together with the best candidates for each therapy are outlined in this article.

PMID- 29222307
TI  - Secondary CNS relapse in diffuse large B-cell lymphoma: defining high-risk
      patients and optimization of prophylaxis strategies.
AB  - Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the
      introduction of rituximab, central nervous system (CNS) relapse continues to
      represent a clinical challenge. A number of studies have evaluated clinical risk
      factors in an attempt to identify high-risk patients to direct CNS staging
      investigations and consider prophylaxis strategies. The CNS International
      Prognostic Index is a robust and reproducible risk model that can identity
      patients at high risk of CNS relapse, but its specificity remains limited.
      Studies are emerging of biomarkers that predict CNS relapse that can be
      integrated with clinical risk models to better identify high-risk patients for
      CNS-directed prophylaxis strategies. Because CNS parenchymal disease is the
      predominant compartment, prophylaxis should include deeply penetrant drugs such
      as high-dose methotrexate. However, this has been associated with toxicity and
      has limited use in older patients. Novel therapies are being tested in primary
      CNS lymphoma with encouraging results and may represent rational strategies to be
      further explored in the prophylaxis setting.

PMID- 29222308
TI  - Hemophilia gene therapy comes of age.
AB  - Concurrent with the development of recombinant factor replacement products, the
      characterization of the F9 and F8 genes over 3 decades ago allowed for the
      development of recombinant factor products and made the hemophilias a target
      disease for gene transfer. The progress of hemophilia gene therapy has been
      announced in 3 American Society of Hematology scientific plenary sessions,
      including the first "cure" in a large animal model of hemophilia B in 1998, first
      in human sustained vector-derived factor IX activity in 2011, and our clinical
      trial results reporting sustained vector-derived factor IX activity well into the
      mild or normal range in 2016. This progression to clinically meaningful success
      combined with numerous ongoing recombinant adeno-associated virus (rAAV)-mediated
      hemophilia gene transfer clinical trials suggest that the goal of gene therapy to
      alter the paradigm of hemophilia care may soon be realized. Although several
      novel therapeutics have recently emerged for hemophilia, gene therapy is unique
      in its potential for a one-time disease-altering, or even curative, treatment.
      This review will focus on the prior progress and current clinical trial
      investigation of rAAV-mediated gene transfer for hemophilia A and B.

PMID- 29222309
TI  - Using pharmacokinetics to individualize hemophilia therapy.
AB  - Prevention and treatment of bleeding in hemophilia requires that plasma clotting
      factor activity of the replaced factor exceeds a defined target level. Most
      clinical decisions in hemophilia are based on implicit or explicit application of
      pharmacokinetic measures. The large interindividual variability in
      pharmacokinetics of factor concentrates suggests that relying on the average
      pharmacokinetic characteristics of factor concentrates would not allow optimizing
      the treatment of individual patients; for example, adjusting the frequency of
      infusions and targeting a specific clotting factor activity level on a case-by
      case basis. However, individual pharmacokinetic profiles are seldom assessed as
      part of routine clinical care. Population pharmacokinetics provide options for
      precise and convenient characterization of pharmacokinetics characteristics of
      factor concentrates, simplified individual pharmacokinetic profiling, and
      individualized dosing. Population pharmacokinetics allow for the incorporation of
      determinants of interpatient variability and reduces the need for extensive
      postinfusion plasma sampling. Barriers to the implementation of population
      pharmacokinetics are the need for concentrate-specific pharmacokinetic models,
      Bayesian calculation power, and specific expertise for production, validation,
      and appraisal of forecasted estimates. Population pharmacokinetics provide an
      important theoretical and practical contribution to tailoring the treatment of
      hemophilia. The need remains for prospective exploration of the clinical impact
      of tailoring hemophilia treatment based on individual pharmacokinetics, and for
      the systematic validation of existing software solutions and concentrate-specific
      models.

PMID- 29222310
TI  - Novel alternate hemostatic agents for patients with inhibitors: beyond bypass
      therapy.
AB  - Inhibitor formation is among the most severe complications of hemophilia
      treatment. With a cumulative incidence of ~30% in those with severe hemophilia A
      and ~3% in those with severe hemophilia B, inhibitors are caused by a T-cell
      response directed against infused coagulation factor; these inhibitors neutralize
      factor VIII or IX activity and disrupt normal hemostasis. Inhibitor patients
      become unresponsive to standard factor treatment and, as an alternative, use
      bypass treatment (eg, recombinant factor VIIa or factor VIII inhibitor bypass
      activity). However, response to bypass agents is poorer and the burden of disease
      is higher, with greater morbidity, hospitalization, cost, and mortality, than in
      noninhibitor patients. Furthermore, inhibitor formation interferes with
      prophylaxis to prevent bleeding episodes and is a contraindication to gene
      therapy. Thus, more effective therapies for inhibitor patients are greatly
      needed. In the last several years, there has been an explosion of novel
      alternative hemostatic agents for hemophilia patients with and without
      inhibitors. These agents take advantage of technologic manipulation of
      coagulation factors and natural anticoagulants to promote hemostasis. The
      approaches include the following: (1) mutants or mimics of coagulation factors,
      rendering them resistant to natural anticoagulants; or (2) knock-down or
      disruption of natural anticoagulants, preventing degradation of coagulation
      factors. The purpose of this article was to review these novel alternative
      hemostatic agents and their mechanisms of action, as well as the preliminary
      pharmacokinetic, safety, and efficacy data available from early-phase clinical
      trials.

PMID- 29222311
TI  - Role of the microenvironment across histological subtypes of NHL.
AB  - Recent progress in next-generation sequencing strategies has revealed the genetic
      landscape of B-cell non-Hodgkin lymphoma, but the tumor microenvironment is
      increasingly recognized as crucial to sustaining malignant B-cell survival and
      growth, subclonal evolution, and drug resistance. The tumor niche is made up of a
      dynamic and organized network of strongly heterogeneous immune and stromal cell
      subsets characterized by specific phenotypic, transcriptomic, and functional
      features. Nonmalignant cell recruitment and plasticity are dictated by lymphoma B
      cells, which convert their surrounding microenvironment into a supportive niche.
      In addition, they are also influenced by the crosstalk between the various
      components of this niche. In agreement with this, the B-cell lymphoma subtype is
      a key determinant of the organization of the tumor niche, but genetic alteration
      patterns, tumor localization, stage of the disease, and treatment strategy may
      also modulate its composition and activity. Moreover, the complex set of
      bidirectional interactions between B cells and their microenvironment has been
      proposed as a promising therapeutic target with the aim of reinforcing antitumor
      immunity and/or of abbrogating the lymphoma-promoting signals delivered by the
      tumor niche.

PMID- 29222312
TI  - Harnessing the power of the immune system in non-Hodgkin lymphoma:
      immunomodulators, checkpoint inhibitors, and beyond.
AB  - Non-Hodgkin lymphoma is a malignancy of B lymphocytes that typically infiltrate
      sites of disease, including the lymph nodes, spleen, and bone marrow. Beyond the
      presence of malignant cells, many immune cells are also present within the tumor
      microenvironment. Although these immune cells have the potential to regulate the
      growth of malignant B cells, intratumoral immune cells are unable to eradicate
      lymphoma cells and most patients with lymphoma have clinical evidence of disease
      progression. Recent data have identified some of the mechanisms that account for
      the suppressed antitumor immune response and have created opportunities for
      treatment to overcome the deficiencies. Two general categories of immunological
      therapies are available. The first approach is to use agents that prevent
      inhibitory signals via immune checkpoint receptors that downregulate immune cell
      function. Blockade of suppressive programmed cell death 1 (PD-1) or CTLA-4
      signaling has resulted in significant clinical activity by allowing intratumoral
      T cells to remain activated and target malignant cells. A second approach is to
      additionally activate T cells that are suboptimally active or suppressed, by
      providing signals through costimulatory molecules including CD27 or CD40 or by
      adding immunostimulatory cytokines. There has been significant heterogeneity in
      the responses to these treatment approaches. Clinical responses are seen in many
      diseases, but the most promising responses have been with PD-1 blockade in
      Hodgkin lymphoma. In other lymphomas, responses are seen but only in a subset of
      patients. Further research is needed to identify the mechanisms that account for
      response and to identify patients most likely to benefit from immune modulation.

PMID- 29222314
TI  - Plasma exchange in thrombotic microangiopathies (TMAs) other than thrombotic
      thrombocytopenic purpura (TTP).
AB  - Thrombotic microangiopathies (TMAs) are a diverse group of disorders that are
      characterized by common clinical and laboratory features. The most commonly
      thought-of TMA is thrombotic thrombocytopenic purpura (TTP). Because of the
      marked improvement in patient mortality associated with the use of therapeutic
      plasma exchange (TPE) in TTP, this therapy has been applied to all of the TMAs.
      The issue, however, is that the pathophysiology varies and in many instances may
      represent a disorder of the endothelium and not the blood; in some cases, the
      pathophysiology is unknown. The use of TPE is further obscured by a lack of
      strong supporting literature on its use, with most consisting of case series and
      case reports; controlled or randomized controlled trials are lacking. Evidence
      supporting the use of TPE in the treatment of TMAs (other than TTP and TMA
      complement mediated) is lacking, and therefore its role is uncertain. With the
      greater availability of genetic testing for mutations involving complement
      regulatory genes and complement pathway components, there seems to be a
      percentage of TMA cases, other than TMA-complement mediated, in which complement
      pathway mutations are involved in some patients. The ability of TPE to remove
      abnormal complement pathway components and replace them with normal components
      may support its use in some patients with TMAs other than TTP and TMA-complement
      mediated.

PMID- 29222313
TI  - Developing T-cell therapies for lymphoma without receptor engineering.
AB  - T-cell therapy has emerged from the bench for the treatment of patients with
      lymphoma. Responses to T-cell therapeutics are regulated by multiple factors,
      including the patient's immune system status and disease stage. Outside of
      engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell
      therapy can be mediated by ex vivo expansion of antigen-specific T cells
      targeting viral and/or nonviral tumor-associated antigens. These approaches are
      contributing to enhanced clinical responses and overall survival. In this review,
      we summarize the available T-cell therapeutics beyond receptor engineering for
      the treatment of patients with lymphoma.

PMID- 29222315
TI  - Extracorporeal photopheresis: cellular therapy for the treatment of acute and
      chronic graft-versus-host disease.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially
      curative option for many disease states. Despite significant improvements in
      strategies used to prevent and treat acute and chronic graft-versus-host disease
      (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly.
      Standard, first-line treatment consists of corticosteroids; beyond this, there is
      little consistency in therapeutic regimens. Current options include the addition
      of various immunosuppressive agents, the use of which puts patients at even
      higher risks for infection and other morbidities. Extracorporeal photopheresis
      (ECP) is a widely used cellular therapy currently approved by the US Food and
      Drug Administration for use in patients with cutaneous T-cell lymphoma; it
      involves the removal of peripherally circulating white blood cells, addition of a
      light sensitizer, exposure to UV light, and return of the cells to the patient.
      This results in a series of events ultimately culminating in transition from an
      inflammatory state to that of tolerance, without global immunosuppression or
      known long-term adverse effects. Large-scale, prospective studies of the use of
      ECP in patients with a/cGVHD are necessary in order to develop the optimal
      treatment regimens.

PMID- 29222316
TI  - HLA donor-specific antibodies in allogeneic hematopoietic stem cell
      transplantation: challenges and opportunities.
AB  - Allogenic hematopoietic stem cell recipients may have preformed antibodies
      directed against foreign HLA antigens. The use of partially HLA-mismatched
      allogeneic hematopoietic stem cell donors allows for the possibility of the
      presence of circulating HLA donor-specific antibodies (DSAs) in the recipient.
      The presence of DSAs at the time of stem cell infusion increases the risk of
      primary graft failure. More recently developed technology using solid phase
      immunoassays (SPIs) with fluorochrome-conjugated beads has greatly improved the
      ability to detect and classify DSAs. When used in combination with the classic
      lymphocytotoxic complement-dependent and flow cytometric crossmatch tests, SPIs
      help provide DSA strength assessment. Parous females frequently harbor DSAs. DSAs
      tend to be of higher intensity when directed against haploidentical first-degree
      relatives. DSA assessment requires frequent monitoring as their relative strength
      can change over time. Although the criteria that constitutes a prohibitive DSA is
      unknown, desensitization techniques can result in engraftment rates as
      experienced in fully HLA-matched allogeneic blood or marrow transplantation
      recipients.

PMID- 29222317
TI  - Thrombocytopenia in hospitalized patients: approach to the patient with
      thrombotic microangiopathy.
AB  - Thrombotic microangiopathies (TMAs), specifically, thrombotic thrombocytopenic
      purpura (TTP) and complement-mediated hemolytic uremic syndrome (CM-HUS) are
      acute life-threatening disorders that require prompt consideration, diagnosis,
      and treatment to improve the high inherent mortality and morbidity. Presentation
      is with microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) and
      variable organ symptoms resulting from microvascular thrombi. Neurological and
      cardiac involvement is most common in TTP and associated with poorer prognosis
      and primarily renal involvement in CM-HUS. TTP is confirmed by severe ADAMTS13
      deficiency (which can be undertaken in real time) and CM-HUS by an abnormality in
      complement regulators, confirmed by mutational analysis (in 60% to 70% of cases)
      or the presence of Factor H antibodies (which may not be available for weeks or
      months). Plasma exchange (PEX) should be started as soon as possible following
      consideration of these TMAs. Differentiation of the diagnosis requires specific
      treatment pathways thereafter (immunosuppression primarily for TTP and complement
      inhibitor therapy for CM-HUS). As the diagnosis is based on MAHAT, there are a
      number of other medical situations that need to be excluded and these are
      discussed within the article. Other differentials presenting as TMAs may also be
      associated with micro- or macrovascular thrombosis, yet are more likely to be due
      to direct endothelial damage, many of which do not have a clear therapeutic
      benefit with PEX.

PMID- 29222318
TI  - Assessing thrombocytopenia in the intensive care unit: the past, present, and
      future.
AB  - Thrombocytopenia is common among patients admitted to the intensive care unit
      (ICU). Multiple pathophysiological mechanisms may contribute, including thrombin
      mediated platelet activation, dilution, hemophagocytosis, extracellular histones,
      ADAMTS13 deficiency, and complement activation. From the clinical perspective,
      the development of thrombocytopenia in the ICU usually indicates serious organ
      system derangement and physiologic decompensation rather than a primary
      hematologic disorder. Thrombocytopenia is associated with bleeding, transfusion,
      and adverse clinical outcomes including death, though few deaths are directly
      attributable to bleeding. The assessment of thrombocytopenia begins by looking
      back to the patient's medical history and presenting illness. This past
      information, combined with careful observation of the platelet trajectory in the
      context of the patient's clinical course, offers clues to the diagnosis and
      prognosis. Management is primarily directed at the underlying disorder and
      transfusion of platelets to prevent or treat clinical bleeding. Optimal platelet
      transfusion strategies are not defined, and a conservative approach is
      recommended.

PMID- 29222319
TI  - HITs and misses in 100 years of heparin.
AB  - Heparin was discovered 100 years ago, and the heparin-induced thrombocytopenia
      syndrome was described 40 years ago. That the most powerful anticoagulant of the
      last century can also produce the most extreme prothrombotic diathesis is but one
      of the paradoxes that surround heparin-induced thrombocytopenia. Standard
      treatment is alternative anticoagulation. Advances continue to be made regarding
      pathophysiology, prevention, and treatment. Currently, an epidemic of
      overdiagnosis threatens the well-being of patients, so efforts to educate
      clinicians on when and how to make this diagnosis are pressing.

PMID- 29222320
TI  - Anticoagulation with VADs and ECMO: walking the tightrope.
AB  - The evolution of devices for mechanical circulatory support (MCS), including
      ventricular assist devices (VADs) for patients with heart failure and
      extracorporeal membrane oxygenation (ECMO) for patients with acute cardiac or
      respiratory failure, has improved survival for subsets of critically ill children
      and adults. The devices are intricate and complex, allowing blood to bypass the
      heart or lungs (or both). As blood flows through these artificial devices, normal
      hemostasis is disrupted, coagulation is promoted, and in the absence of
      anticoagulation, a thrombus may form in the device, resulting in device failure
      or embolic stroke. Therefore, anticoagulation is necessary to prevent thrombus
      formation and maintain device function. However, patients on MCS also have very
      high bleeding rates. Titrating anticoagulation to prevent hemorrhagic
      complications and thrombotic events can be a challenge, and hematologists may be
      consulted in complex cases. Substantial variability remains in the approach to
      anticoagulant and antiplatelet therapy for patients on MCS, largely because of
      the lack of high-quality data. Improvements in the design and manufacture of
      these devices, as well as in the individualized titration of antithrombotic
      intensity, are expected to enhance outcomes. Several factors pertaining to both
      the device and the patient (adult and children) should be considered when
      attempting to optimize this delicate balance.

PMID- 29222321
TI  - Thrombectomy and thrombolysis for the prevention and treatment of postthrombotic
      syndrome.
AB  - Postthrombotic syndrome (PTS) is a frequent complication of lower-extremity deep
      vein thrombosis (DVT), occurring in approximately 40% of patients despite the use
      of anticoagulant therapy. PTS causes significant impairment of patients' health
      related quality of life, and no evidence-based therapies have been consistently
      effective. Catheter-directed thrombolysis and thrombectomy have been shown to
      remove acute thrombus, and it has been hypothesized they could prevent or reduce
      PTS. However, because these procedures can be associated with complications,
      mainly bleeding, randomized trial data are needed to determine when they should
      be used. In this article, I summarize the current status of thrombus removal
      procedures for DVT to provide contemporary guidance to clinicians seeking to
      individualize treatment decisions for their patients.

PMID- 29222322
TI  - Inferior vena cava filter use and patient safety: legacy or science?
AB  - There has been a dramatic increase in vena cava filter (VCF) use over the past 20
      years in the absence of evidence that filters provide a net patient benefit or
      are required in most cases. This increase is largely attributable to the
      availability of retrievable filters and expanded indications, particularly as
      primary prophylaxis in patients thought to be at high risk of pulmonary embolism.
      Substantial variability in VCF use, unrelated to patient clinical factors, has
      been shown between hospitals, from region to region, and among various countries.
      Despite the lack of direct evidence for the benefit of VCFs for any indication,
      it is appropriate to insert a retrievable VCF in patients with a recent proximal
      deep vein thrombosis and an absolute contraindication to therapeutic
      anticoagulation and then to remove the filter once the bleeding risk decreases
      and the patient has been anticoagulated. Unfortunately, a high proportion of
      retrievable filters are not removed, even after the reason for their placement
      has long passed. Retrievable filters are associated with substantial rates of
      complications if they are not removed, including penetration of the vena caval
      wall, fracture and embolization of filter fragments, and caval occlusion. Patient
      safety priorities and medical-legal concerns mandate careful selection of
      patients for VCF placement and removal shortly after anticoagulation has been
      initiated.

PMID- 29222323
TI  - Graft versus tumor effects and why people relapse.
AB  - Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of
      allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of
      cellular immunotherapy. The antitumor effect against hematologic malignancies is
      mediated by a polyclonal T-cell response targeting polymorphic antigens expressed
      on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the
      patient after transplantation unharmed. Fortunately, hematopoietic tissues
      (including malignant hematopoietic cell populations) are relatively susceptible
      to T-cell recognition. If, however, nonhematopoietic tissues of the recipient are
      targeted as well, graft-versus-host disease (GVHD) will occur. The balance
      between GVT and GVHD is influenced by the genetic disparity between donor and
      recipient, the number and origin of professional antigen-presenting cells
      provoking the immune response, the target antigen specificity, magnitude and
      diversity of the response, and the in vivo inflammatory environment, whereas
      inhibitory factors may silence the immune response. Manipulation of each of these
      factors will determine the balance between GVT and GVHD.

PMID- 29222324
TI  - Pharmacologic agents to prevent and treat relapse after allogeneic hematopoietic
      cell transplantation.

PMID- 29222325
TI  - Cells to prevent/treat relapse following allogeneic stem cell transplantation.
AB  - Relapse of cancer remains one of the primary causes of treatment failure and
      mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A
      multitude of approaches have been used in the management of posttransplant
      relapse. This review focuses on recent data with cellular therapies designed to
      treat or prevent posttransplant relapse of hematologic malignancies, although
      many of these therapeutic approaches also have applications to solid tumors and
      in the nontransplant setting. Currently available cell therapies include second
      transplant, natural killer cells, monocyte-derived dendritic cell vaccines, and
      lymphocytes via donor lymphocyte infusion, antigen-primed cytotoxic T
      lymphocytes, cytokine-induced killer cells, marrow-infiltrating lymphocytes, and
      chimeric antigen receptor T cells. These treatment options offer the prospect for
      improved relapse-free survival after HSCT.

PMID- 29222326
TI  - Acquired ribosomopathies in leukemia and solid tumors.
AB  - A mutation in the gene encoding the small subunit-associated ribosomal protein
      RPS19, leading to RPS19 haploinsufficiency, is one of the ribosomal protein gene
      defects responsible for the rare inherited bone marrow failure syndrome Diamond
      Blackfan anemia (DBA). Additional inherited and acquired defects in ribosomal
      proteins (RPs) continue to be identified and are the basis for a new class of
      diseases called the ribosomopathies. Acquired RPS14 haploinsufficiency has been
      found to be causative of the bone marrow failure found in 5q- myelodysplastic
      syndromes. Both under- and overexpression of RPs have also been implicated in
      several malignancies. This review will describe the somatic ribosomopathies that
      have been found to be associated with a variety of solid tumors as well as
      leukemia and will review cancers in which over- or underexpression of these
      proteins seem to be associated with outcome.

PMID- 29222327
TI  - Mitochondrially produced ATP affects stem cell pluripotency via Actl6a-mediated
      histone acetylation.
AB  - ATP is mainly generated by glycolysis in pluripotent stem cells (PSCs) and is
      consumed to maintain cell viability. Differences in mitochondrial activity among
      induced (i)PSCs with different degrees of pluripotency are poorly understood. In
      this study, by comparing gene expression and mitochondrial activity among iPSCs
      with different degrees of pluripotency, we found that mitochondrial complex I
      gene expression, complex I activity, and cellular ATP levels were much higher in
      fully pluripotent stem cell lines than in partially pluripotent stem cell lines.
      Actin-like protein 6a (Actl6a), a component of ATP-dependent chromatin remodeling
      and histone acetylation complexes, was more highly expressed in fully pluripotent
      stem cell lines. ATP promoted Actl6a expression and histone acetylation. Actl6a
      knockdown reduced the pluripotency of embryonic stem cells (ESCs), and this
      reduction could not be rescued by the addition of ATP. Furthermore, inhibiting
      ATP formation by treatment with rotenone reduced the pluripotency of ESCs. These
      data suggest that the abundance of mitochondrially produced ATP affects stem cell
      pluripotency via Actl6a-mediated histone acetylation.-Zhang, Y., Cui, P., Li, Y.,
      Feng, G., Tong, M., Guo, L., Li, T., Liu, L., Li, W., Zhou, Q. Mitochondrially
      produced ATP affects stem cell pluripotency via Actl6a-mediated histone
      acetylation.

PMID- 29222328
TI  - Fructose and glucose can regulate mammalian target of rapamycin complex 1 and
      lipogenic gene expression via distinct pathways.
AB  - Although calorically equivalent to glucose, fructose appears to be more
      lipogenic, promoting dyslipidemia, fatty liver disease, cardiovascular disease,
      and diabetes. To better understand how fructose induces lipogenesis, we compared
      the effects of fructose and glucose on mammalian target of rapamycin complex 1
      (mTORC1), which appeared to have both positive and negative effects on lipogenic
      gene expression. We found that fructose acutely and transiently suppressed mTORC1
      signaling in vitro and in vivo The constitutive activation of mTORC1 reduced
      hepatic lipogenic gene expression and produced hypotriglyceridemia after 1 week
      of fructose feeding. In contrast, glucose did not suppress mTORC1, and the
      constitutive activation of mTORC1 failed to suppress plasma triglycerides after 1
      week of glucose feeding. Thus, these data reveal fundamental differences in the
      signaling pathways used by fructose and glucose to regulate lipid metabolism.

PMID- 29222329
TI  - Glutaminolysis is required for transforming growth factor-beta1-induced
      myofibroblast differentiation and activation.
AB  - Myofibroblasts participate in physiological wound healing and pathological
      fibrosis. Myofibroblast differentiation is characterized by the expression of
      alpha-smooth muscle actin and extracellular matrix proteins and is dependent on
      metabolic reprogramming. In this study, we explored the role of glutaminolysis
      and metabolites of TCA in supporting myofibroblast differentiation.
      Glutaminolysis converts Gln into alpha-ketoglutarate (alpha-KG), a critical
      intermediate in the TCA cycle. Increases in the steady-state concentrations of
      TCA cycle metabolites including alpha-KG, succinate, fumarate, malate, and
      citrate were observed in TGF-beta1-differentiated myofibroblasts. The
      concentration of glutamate was also increased in TGF-beta1-differentiated
      myofibroblasts compared with controls, whereas glutamine levels were decreased,
      suggesting enhanced glutaminolysis. This was associated with TGF-beta1-induced
      expression of the glutaminase (GLS) isoform, GLS1, which converts Gln into
      glutamate, at both the mRNA and protein levels. The stimulation of GLS1
      expression by TGF-beta1 was dependent on both SMAD3 and p38 mitogen-activated
      protein kinase activation. Depletion of extracellular Gln prevented TGF-beta1
      induced myofibroblast differentiation. The removal of extracellular Gln
      postmyofibroblast differentiation decreased the expression of the profibrotic
      markers fibronectin and hypoxia-inducible factor-1alpha and reversed TGF-beta1
      induced metabolic reprogramming. Silencing of GLS1 expression, in the presence of
      Gln, abrogated TGF-beta1-induced expression of profibrotic markers. Treatment of
      GLS1-deficient myofibroblasts with exogenous glutamate or alpha-KG restored TGF
      beta1-induced expression of profibrotic markers in GLS1-deficient myofibroblasts.
      Together, these data demonstrate that glutaminolysis is a critical component of
      myofibroblast metabolic reprogramming that regulates myofibroblast
      differentiation.

PMID- 29222330
TI  - Discovery of stimulator binding to a conserved pocket in the heme domain of
      soluble guanylyl cyclase.
AB  - Soluble guanylyl cyclase (sGC) is the receptor for nitric oxide and a highly
      sought-after therapeutic target for the management of cardiovascular diseases.
      New compounds that stimulate sGC show clinical promise, but where these
      stimulator compounds bind and how they function remains unknown. Here, using a
      photolyzable diazirine derivative of a novel stimulator compound, IWP-051, and MS
      analysis, we localized drug binding to the beta1 heme domain of sGC proteins from
      the hawkmoth Manduca sexta and from human. Covalent attachments to the stimulator
      were also identified in bacterial homologs of the sGC heme domain, referred to as
      H-NOX domains, including those from Nostoc sp. PCC 7120, Shewanella oneidensis,
      Shewanella woodyi, and Clostridium botulinum, indicating that the binding site is
      highly conserved. The identification of photoaffinity-labeled peptides was aided
      by a signature MS fragmentation pattern of general applicability for unequivocal
      identification of covalently attached compounds. Using NMR, we also examined
      stimulator binding to sGC from M. sexta and bacterial H-NOX homologs. These data
      indicated that stimulators bind to a conserved cleft between two subdomains in
      the sGC heme domain. L12W/T48W substitutions within the binding pocket resulted
      in a 9-fold decrease in drug response, suggesting that the bulkier tryptophan
      residues directly block stimulator binding. The localization of stimulator
      binding to the sGC heme domain reported here resolves the longstanding question
      of where stimulators bind and provides a path forward for drug discovery.

PMID- 29222331
TI  - A hypertension-associated mitochondrial DNA mutation introduces an m1G37
      modification into tRNAMet, altering its structure and function.
AB  - Defective nucleotide modifications of mitochondrial tRNAs have been associated
      with several human diseases, but their pathophysiology remains poorly understood.
      In this report, we investigated the pathogenic molecular mechanism underlying a
      hypertension-associated 4435A->G mutation in mitochondrial tRNAMet The m.4435A->G
      mutation affected a highly conserved adenosine at position 37, 3' adjacent to the
      tRNA's anticodon, which is important for the fidelity of codon recognition and
      stabilization. We hypothesized that the m.4435A->G mutation introduced an m1G37
      modification of tRNAMet, altering its structure and function. Primer extension
      and methylation activity assays indeed confirmed that the m.4435A->G mutation
      created a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of
      tRNAMet We found that this mutation altered the tRNAMet structure, indicated by
      an increased melting temperature and electrophoretic mobility of the mutated tRNA
      compared with the wildtype molecule. We demonstrated that cybrid cell lines
      carrying the m.4435A->G mutation exhibited significantly decreased efficiency in
      aminoacylation and steady-state levels of tRNAMet, as compared with those of
      control cybrids. The aberrant tRNAMet metabolism resulted in variable decreases
      in mitochondrial DNA (mtDNA)-encoded polypeptides in the mutant cybrids.
      Furthermore, we found that the m.4435A->G mutation caused respiratory deficiency,
      markedly diminished mitochondrial ATP levels and membrane potential, and
      increased the production of reactive oxygen species in mutant cybrids. These
      results demonstrated that an aberrant m1G37 modification of mitochondrial tRNAMet
      affected the structure and function of its tRNA and consequently altered
      mitochondrial function. Our findings provide critical insights into the
      pathophysiology of maternally inherited hypertension, which is manifested by the
      deficient tRNA nucleotide modification.

PMID- 29222332
TI  - Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the
      immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers.
AB  - To provide protective immunity against circulating primary HIV-1 strains, a
      vaccine most likely has to induce broadly neutralizing antibodies to the HIV-1
      envelope glycoprotein (Env) spike. Recombinant Env trimers such as the prototype
      BG505 SOSIP.664 that closely mimic the native Env spike can induce autologous
      neutralizing antibodies (NAbs) against relatively resistant (tier 2) primary
      viruses. Ideally, Env immunogens should present broadly neutralizing antibody
      epitopes but limit the presentation of immunodominant non-NAb epitopes that might
      induce off-target and potentially interfering responses. The V3 loop in gp120 is
      such a non-NAb epitope that can effectively elicit non-NAbs when animals are
      immunized with SOSIP.664 trimers. V3 immunogenicity can be diminished, but not
      abolished, by reducing the conformational flexibility of trimers via targeted
      sequence changes, including an A316W substitution in V3, that create the
      SOSIP.v4.1 and SOSIP.v5.2 variants. Here, we further modified these trimer
      designs by introducing leucine residues at V3 positions 306 and 308 to create
      hydrophobic interactions with the tryptophan residue at position 316 and with
      other topologically proximal sites in the V1V2 domain. Together, these
      modifications further stabilized the resulting SOSIP.v5.2 S306L/R308L trimers in
      the prefusion state in which V3 is sequestered. When we tested these trimers as
      immunogens in rabbits, the induction of V3 non-NAbs was significantly reduced
      compared with the SOSIP.v5.2 trimers and even more so compared with the SOSIP.664
      prototype, without affecting the autologous NAb response. Hence, these additional
      trimer sequence modifications may be beneficial for immunization strategies that
      seek to minimize off-target non-NAb responses.

PMID- 29222333
TI  - Structural determinants of bacterial lytic polysaccharide monooxygenase
      functionality.
AB  - Bacterial lytic polysaccharide monooxygenases (LPMO10s) use redox chemistry to
      cleave glycosidic bonds in the two foremost recalcitrant polysaccharides found in
      nature, namely cellulose and chitin. Analysis of correlated mutations revealed
      that the substrate-binding and copper-containing surface of LPMO10s composes a
      network of co-evolved residues and interactions, whose roles in LPMO
      functionality are unclear. Here, we mutated a subset of these correlated residues
      in a newly characterized C1/C4-oxidizing LPMO10 from Micromonospora aurantiaca
      (MaLPMO10B) to the corresponding residues in strictly C1-oxidizing LPMO10s. We
      found that surface properties near the catalytic copper, i.e. side chains likely
      to be involved in substrate positioning, are major determinants of the C1:C4
      ratio. Several MaLPMO10B mutants almost completely lost C4-oxidizing activity
      while maintaining C1-oxidizing activity. These mutants also lost chitin-oxidizing
      activity, which is typically observed for C1/C4-oxidizing, but not for C1
      oxidizing, cellulose-active LPMO10s. Selective loss in C1-oxidizing activity was
      not observed. Additional mutational experiments disclosed that neither truncation
      of the MaLPMO10B family 2 carbohydrate-binding module nor mutations altering
      access to the solvent-exposed axial copper coordination site significantly change
      the C1:C4 ratio. Importantly, several of the mutations that altered interactions
      with the substrate exhibited reduced stability. This effect could be explained by
      productive substrate binding that protects LPMOs from oxidative self
      inactivation. We discuss these stability issues in view of recent findings on
      LPMO catalysis, such as the involvement of H2O2 Our results show that residues on
      the substrate-binding surface of LPMOs have co-evolved to optimize several of the
      interconnected properties: substrate binding and specificity, oxidative
      regioselectivity, catalytic efficiency, and stability.

PMID- 29222336
TI  - Taking control of alcohol-related emergency department visits.

PMID- 29222334
TI  - Cellular FLIP long isoform (cFLIPL)-IKKalpha interactions inhibit IRF7
      activation, representing a new cellular strategy to inhibit IFNalpha expression.
AB  - Interferon alpha (IFNalpha) is important for antiviral and anticancer defenses.
      However, overproduction is associated with autoimmune disorders. Thus, the cell
      must precisely up- and down-regulate IFNalpha to achieve immune system
      homeostasis. The cellular FLICE-like inhibitory protein (cFLIP) is reported to
      inhibit IFNalpha production. However, the mechanism for this antagonism remained
      unknown. The goal here was to identify this mechanism. Here we examined the
      signal transduction events that occur during TLR9-induced IRF7 activation. The
      cFLIP long isoform (cFLIPL) inhibited the expression of IRF7-controlled natural
      or synthetic genes in several cell lines, including those with abundant IRF7
      protein levels (e.g. dendritic cells). cFLIPL inhibited IRF7 phosphorylation;
      however, cFLIPL-IRF7 interactions were not detectable, implying that cFLIPL acted
      upstream of IRF7 dimerization. Interestingly, cFLIPL co-immunoprecipitated with
      IKKalpha, and these interactions correlated with a loss of IKKalpha-IRF7
      interactions. Thus, cFLIP appears to bind to IKKalpha to prevent IKKalpha from
      phosphorylating and activating IRF7. To the best of our knowledge, this is the
      first report of a cellular protein that uses this approach to inhibit IRF7
      activation. Perhaps this cFLIP property could be engineered to minimize the
      deleterious effects of IFNalpha expression that occur during certain autoimmune
      disorders.

PMID- 29222337
TI  - Menopausal Hormone Therapy and Cardiovascular Disease: Unraveling the Role of Age
      and Time Since Menopause Onset.

PMID- 29222335
TI  - Single-cell transcriptome sequencing reveals that cell division cycle 5-like
      protein is essential for porcine oocyte maturation.
AB  - The brilliant cresyl blue (BCB) test is used in both basic biological research
      and assisted reproduction to identify oocytes likely to be developmentally
      competent. However, the underlying molecular mechanism targeted by the BCB test
      is still unclear. To explore this question, we first confirmed that BCB-positive
      porcine oocytes had higher rates of meiotic maturation, better rates of cleavage
      and development into blastocysts, and lower death rates. Subsequent single-cell
      transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes
      identified 155 genes that were significantly differentially expressed between BCB
      negative and BCB-positive oocytes. These included genes such as cdc5l, ldha,
      spata22, rgs2, paip1, wee1b, and hsp27, which are enriched in functionally
      important signaling pathways including cell cycle regulation, oocyte meiosis,
      spliceosome formation, and nucleotide excision repair. In BCB-positive GV oocytes
      that additionally had a lower frequency of DNA double-strand breaks, the CDC5L
      protein was significantly more abundant. cdc5l/CDC5L inhibition by short
      interference (si)RNA or antibody microinjection significantly impaired porcine
      oocyte meiotic maturation and subsequent parthenote development. Taken together,
      our single-oocyte sequencing data point to a potential new role for CDC5L in
      porcine oocyte meiosis and early embryo development, and supports further
      analysis of this protein in the context of the BCB test.

PMID- 29222338
TI  - Blood Sample Transportation by Pneumatic Transportation Systems: A Systematic
      Literature Review.
AB  - BACKGROUND: Pneumatic transportation systems (PTSs) are increasingly used for
      transportation of blood samples to the core laboratory. Many studies have
      investigated the impact of these systems on different types of analyses, but to
      elucidate whether PTSs in general are safe for transportation of blood samples,
      existing literature on the subject was systematically assessed. METHODS: A
      systematic literature review was conducted following the preferred reporting
      items for systematic reviews and metaanalyses (PRISMA) Statement guidelines to
      gather studies investigating the impact of PTS on analyses in blood samples.
      Studies were extracted from PubMed and Embase. The search period ended November
      2016. RESULTS: A total of 39 studies were retrieved. Of these, only 12 studies
      were conducted on inpatients, mainly intensive care unit patients. Blood gases,
      hematology, and clinical chemistry were well investigated, whereas coagulation,
      rotational thromboelastometry, and platelet function in acutely ill patients were
      addressed by only 1 study each. Only a few parameters were affected in a
      clinically significant way (clotting time parameter in extrinsic system
      thromboelastometry, pO2 in blood gas, multiplate analysis, and the hemolysis
      index). CONCLUSIONS: Owing to their high degree of heterogeneity, the retrieved
      studies were unable to supply evidence for the safety of using PTSs for blood
      sample transportation. In consequence, laboratories need to measure and document
      the actual acceleration forces in their existing PTS, instituting quality target
      thresholds for these measurements such as acceleration vector sums. Computer
      modeling might be applied to the evaluation of future PTS installations. With the
      increasing use of PTS, a harmonized, international recommendation on this topic
      is warranted.

PMID- 29222340
TI  - Evolution of Materials in Novel Point-of-Care Diagnostics.

PMID- 29222339
TI  - The Biological Variation Data Critical Appraisal Checklist: A Standard for
      Evaluating Studies on Biological Variation.
AB  - BACKGROUND: Concern has been raised about the quality of available biological
      variation (BV) estimates and the effect of their application in clinical
      practice. A European Federation of Clinical Chemistry and Laboratory Medicine
      Task and Finish Group has addressed this issue. The aim of this report is to (a)
      describe the Biological Variation Data Critical Appraisal Checklist (BIVAC),
      which verifies whether publications have included all essential elements that may
      impact the veracity of associated BV estimates, (b) use the BIVAC to critically
      appraise existing BV publications on enzymes, lipids, kidney, and diabetes
      related measurands, and (c) apply metaanalysis to deliver a global within-subject
      BV (CVI) estimate for alanine aminotransferase (ALT). METHODS: In the BIVAC,
      publications were rated as A, B, C, or D, indicating descending compliance for 14
      BIVAC quality items, focusing on study design, methodology, and statistical
      handling. A D grade indicated that associated BV estimates should not be applied
      in clinical practice. Systematic searches were applied to identify BV studies for
      28 different measurands. RESULTS: In total, 128 publications were identified,
      providing 935 different BV estimates. Nine percent achieved D scores. Outlier
      analysis and variance homogeneity testing were scored as C in >60% of 847 cases.
      Metaanalysis delivered a CVI estimate for ALT of 15.4%. CONCLUSIONS: Application
      of BIVAC to BV publications identified deficiencies in required study detail and
      delivery, especially for statistical analysis. Those deficiencies impact the
      veracity of BV estimates. BV data from BIVAC-compliant studies can be combined to
      deliver robust global estimates for safe clinical application.

PMID- 29222341
TI  - Spherical Nucleic Acids: Adding a New Dimension to Nucleic Acids and Clinical
      Chemistry.

PMID- 29222342
TI  - Regulation of Crossover Frequency and Distribution during Meiotic Recombination.
AB  - Crossover recombination is essential for generating genetic diversity and
      promoting accurate chromosome segregation during meiosis. The process of
      crossover recombination is tightly regulated and is initiated by the formation of
      programmed meiotic DNA double-strand breaks (DSBs). The number of DSBs is around
      10-fold higher than the number of crossovers in most species, because only a
      limited number of DSBs are repaired as crossovers during meiosis. Moreover,
      crossovers are not randomly distributed. Most crossovers are located on
      chromosomal arm regions and both centromeres and telomeres are usually devoid of
      crossovers. Either loss or mislocalization of crossovers frequently results in
      chromosome nondisjunction and subsequent aneuploidy, leading to infertility,
      miscarriages, and birth defects such as Down syndrome. Here, we will review
      aspects of crossover regulation observed in most species and then focus on
      crossover regulation in the nematode Caenorhabditis elegans in which both the
      frequency and distribution of crossovers are tightly controlled. In this system,
      only a single crossover is formed, usually at an off-centered position, between
      each pair of homologous chromosomes. We have identified C. elegans mutants with
      deregulated crossover distribution, and we are analyzing crossover control by
      using an inducible single DSB system with which a single crossover can be
      produced at specific genomic positions. These combined studies are revealing
      novel insights into how crossover position is linked to accurate chromosome
      segregation.

PMID- 29222343
TI  - Bacterial cyclic beta-(1,2)-glucans sequester iron to protect against iron
      induced toxicity.
AB  - Cellular iron homeostasis is critical for survival and growth. Bacteria employ a
      variety of strategies to sequester iron from the environment and to store
      intracellular iron surplus that can be utilized in iron-restricted conditions
      while also limiting the potential for the production of iron-induced reactive
      oxygen species (ROS). Here, we report that membrane-derived oligosaccharide (mdo)
      glucan, an intrinsic component of Gram-negative bacteria, sequesters the ferrous
      form of iron. Iron-binding, uptake, and localization experiments indicated that
      both secreted and periplasmic beta-(1,2)-glucans bind iron specifically and
      promote growth under iron-restricted conditions. Xanthomonas campestris and
      Escherichia coli mutants blocked in the production of beta-(1,2)-glucan
      accumulate low amounts of intracellular iron under iron-restricted conditions,
      whereas they exhibit elevated ROS production and sensitivity under iron-replete
      conditions. Our results reveal a critical role of glucan in intracellular iron
      homeostasis conserved in Gram-negative bacteria.

PMID- 29222344
TI  - TRIP6 inhibits Hippo signaling in response to tension at adherens junctions.
AB  - The transcriptional co-activator YAP controls cell proliferation, survival, and
      tissue regeneration in response to changes in the mechanical environment. It is
      not known how mechanical stimuli such as tension are sensed and how the signal is
      transduced to control YAP activity. Here, we show that the LIM domain protein
      TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to
      promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed
      that vinculin at adherens junctions becomes activated by mechanical tension. We
      show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens
      junctions and stimulating its binding to and inhibition of LATS1/2 in response to
      tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1
      from recruiting the LATS1/2 activating kinases MST1/2. Together, these findings
      reveal a novel pathway that responds to tension at adherens junctions to control
      Hippo pathway signaling.

PMID- 29222345
TI  - Type VI secretion system sheath inter-subunit interactions modulate its
      contraction.
AB  - Secretion systems are essential for bacteria to survive and manipulate their
      environment. The bacterial type VI secretion system (T6SS) generates the force
      needed for protein translocation by the contraction of a long polymer called
      sheath. The sheath is a six-start helical assembly of interconnected VipA/VipB
      subunits. The mechanism of T6SS sheath contraction is unknown. Here, we show that
      elongating the N-terminal VipA linker or eliminating charge of a specific VipB
      residue abolishes sheath contraction and delivery of effectors into target cells.
      Mass spectrometry analysis identified the inner tube protein Hcp, spike protein
      VgrG, and other components of the T6SS baseplate significantly enriched in
      samples of the stable non-contractile sheaths. The ability to lock the T6SS in
      the pre-firing state opens new possibilities for understanding its mode of
      action.

PMID- 29222346
TI  - Adiposity, Inflammation, and Breast Cancer Pathogenesis in Asian Women.
AB  - Obesity is associated with white adipose tissue (WAT) inflammation in the breast,
      elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic
      changes that predispose to breast cancer development. We examined whether WAT
      inflammation and its associated systemic effects correlate with body fat levels
      in an Asian population where body mass index (BMI) is not an accurate assessment
      of obesity and cancer risk. We also investigated whether biologic differences
      could account for the greater proportion of premenopausal estrogen receptor (ER)
      positive breast cancer in Asian versus Western countries. Breast WAT and fasting
      blood were prospectively collected from Taiwanese women undergoing mastectomy for
      breast cancer treatment. Body composition was measured in a subgroup using
      bioelectrical impedance analysis. WAT inflammation was defined by the presence of
      crown-like structures of the breast, which are composed of dead or dying
      adipocytes surrounded by macrophages. Findings were compared with U.S. Caucasian
      women. In the Taiwanese cohort (n = 72), breast WAT inflammation was present in
      31 (43%) women and was associated with elevated BMI (P < 0.01) and increased
      levels of body fat (P < 0.01), C-reactive protein (P = 0.02), triglycerides (P <
      0.01), insulin resistance scores (P = 0.04), and lower HDL cholesterol (P <
      0.01). ER+ tumors were associated with greater body fat versus other subtypes (P
      = 0.03). Compared with U.S. Caucasians (n = 267), Taiwanese women had larger
      breast adipocytes despite lower BMI after adjusting for BMI and menopausal status
      (P = 0.01). A subclinical inflammatory state associated with increased adiposity
      and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian
      women. Cancer Prev Res; 11(4); 227-36. (c)2017 AACR.

PMID- 29222349
TI  - Inequity in biological DMARD prescription for spondyloarthritis across the globe:
      results from the ASAS-COMOSPA study.
AB  - OBJECTIVES: The value of biological disease-modifying antirheumatic drugs
      (bDMARDs) in spondyloarthritis (SpA) is well recognised, but global access to
      these treatments can be limited due to high costs and other factors. This study
      explores country variation in the use of bDMARDs in SpA in relation to country
      level socioeconomic factors. METHODS: Patients fulfilling the Assessment in
      SpondyloArthritis International Society (ASAS) SpA criteria in the multinational,
      cross-sectional ASAS Comorbidities in Spondyloarthritis study were studied.
      Current use of bDMARDs or conventional synthetic DMARDs (csDMARDs) was
      investigated in separate models, with multilevel logistic regression analysis,
      taking the country level into account. Contribution of socioeconomic factors,
      including country health expenditures, gross domestic product and human
      development index as independent country-level factors, was explored
      individually, in models adjusted for sociodemographic as well as clinical
      variables. RESULTS: In total, 3370 patients from 22 countries were included (mean
      (SD) age 43 (14) years; 66% male; 88% axial disease). Across countries, 1275
      (38%) patients were bDMARD users. Crude mean bDMARD use varied between 5% (China)
      to 74% (Belgium). After adjustment for relevant sociodemographic and clinical
      variables, important variation in bDMARD use across countries remained (P<0.001).
      Country-level socioeconomic factors, specifically higher health expenditures,
      were related to higher bDMARD uptake, though not meeting statistical significance
      (OR 1.96; 95% CI 0.94 to 4.10). csDMARD uptake was significantly lower in
      countries with higher health expenditures (OR 0.32; 95% CI 0.15 to 0.65). Similar
      trends were seen with the other socioeconomic variables. CONCLUSIONS: There
      remains important residual variation across countries in bDMARD uptake of
      patients with SpA followed in specialised SpA centres. This is independent of
      well-known factors for bDMARD use such as clinical and country-level
      socioeconomic factors.

PMID- 29222347
TI  - Pioglitazone Inhibits Periprostatic White Adipose Tissue Inflammation in Obese
      Mice.
AB  - Obesity is associated with an increased incidence of high-grade prostate cancer
      and poor prognosis for prostate cancer patients. Recently, we showed that obesity
      related periprostatic white adipose tissue (WAT) inflammation, characterized by
      crown-like structures (CLS) consisting of dead or dying adipocytes surrounded by
      macrophages, was associated with high-grade prostate cancer. It is possible,
      therefore, that agents that suppress periprostatic WAT inflammation will alter
      the development or progression of prostate cancer. Pioglitazone, a ligand of
      PPARgamma, is used to treat diabetes and possesses anti-inflammatory properties.
      Here, our main objectives were to determine whether pioglitazone inhibited
      obesity-related periprostatic WAT inflammation in mice and then to elucidate the
      underlying mechanism. Treatment with pioglitazone reduced the density of CLS in
      periprostatic fat and suppressed levels of TNFalpha, TGFbeta, and the chemokine
      monocyte chemoattractant protein-1 (MCP-1). Importantly, the ability of
      pioglitazone to suppress periprostatic WAT inflammation was abrogated in MCP-1
      knockout mice. Pioglitazone caused dose-dependent induction of both adiponectin,
      an anti-inflammatory adipokine, and its receptor AdipoR2 in cultured 3T3-L1 cells
      and in periprostatic WAT of obese mice. Pioglitazone blocked TNFalpha-mediated
      induction of MCP-1 in 3T3-L1 cells, an effect that was attenuated when either
      adiponectin or AdipoR2 were silenced. Taken together, pioglitazone-mediated
      induction of adiponectin suppressed the elevation in MCP-1 levels, thereby
      attenuating obesity-related periprostatic WAT inflammation. These findings
      strengthen the rationale for future efforts to determine whether targeting the
      PPARgamma-adiponectin-MCP-1 axis will decrease periprostatic adipose inflammation
      and thereby reduce the risk of high-grade prostate cancer or improve outcomes for
      men with prostate cancer. Cancer Prev Res; 11(4); 215-26. (c)2017 AACR.

PMID- 29222350
TI  - Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes.
AB  - OBJECTIVES: Leflunomide is known to be embryotoxic and teratogenic in rodents.
      However, there is less evidence in humans. We quantified the risk of major
      congenital malformation (MCM), prematurity, low birth weight (LBW) and
      spontaneous abortion associated with leflunomide exposure during pregnancy in
      humans. METHODS: From a cohort of 289 688 pregnancies in Montreal, Quebec,
      Canada, from 1998 to 2015, first-trimester leflunomide exposure and other
      antirheumatic drug exposures were studied for their association with MCM and
      spontaneous abortions. Also second or third-trimester leflunomide exposures were
      examined for associations with prematurity and LBW. Logistic regression model
      based generalised estimating equations were used. RESULTS: 51 pregnancies were
      exposed to leflunomide during the first trimester, and 21 during the second/third
      trimesters. Adjusting for potential confounders, use of leflunomide during the
      first trimester of pregnancy was not associated with the risk of MCM (adjusted OR
      (aOR) 0.97, 95% CI 0.81 to 1.16; 5 exposed cases). No association was found
      between second/third-trimester exposure to leflunomide and the risk of
      prematurity (aOR 4.03, 95% CI 0.91 to 17.85; 7 exposed cases) nor LBW (aOR 1.06,
      95%CI 0.90 to 1.25; 8 exposed cases). Pregnancy exposure to leflunomide was also
      not associated with the risk of spontaneous abortion (aOR 1.09, 95% CI 0.90 to
      1.32; 11 exposed cases). CONCLUSIONS: Maternal exposure to leflunomide during
      pregnancy was not associated with statistically significant increased risk of
      MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively
      few women were exposed to leflunomide during pregnancy in this cohort, caution
      remains warranted.

PMID- 29222348
TI  - Insulin degrading enzyme contributes to the pathology in a mixed model of Type 2
      diabetes and Alzheimer's disease: possible mechanisms of IDE in T2D and AD.
AB  - Insulin degrading enzyme (IDE) is believed to act as a junction point of Type 2
      diabetes (T2D) and Alzheimer's disease (AD); however, the underlying mechanism
      was not completely clear yet. Transgenic APPSwe/PS1 mice were used as the AD
      model and were treated with streptozocin/streptozotocin (STZ) to develop a mixed
      mice model presenting both AD and T2D. Morris Water Maze (MWM) and recognition
      task were performed to trace the cognitive function. The detection of fasting
      plasma glucose (FPG) and plasma insulin concentration, and oral glucose tolerance
      test (OGTT) were used to trace the metabolism evolution. Abeta40 and Abeta42 were
      quantified by colorimetric ELISA kits. The mRNA or protein expression levels were
      determined by quantitative real-time RT-PCR and Western blotting analysis
      respectively. T2D contributes to the AD progress by accelerating and worsening
      spatial learning and recognition impairments. Metabolic parameters and glucose
      tolerance were significantly changed in the presence of the AD and T2D. The
      expression levels of IDE, PPARgamma, and AMPK were down-regulated in mice with AD
      and T2D. PPARgamma activator rosiglitazone (RSZ) or AMPK activator AICAR
      increased the expression level of IDE and decreased Abeta levels in mice with AD
      and T2D. RSZ or AICAR treatment also alleviated the spatial learning and
      recognition impairments in AD and T2D mice. Our results found that, in the mice
      with T2D and AD, the activators of PPARgamma/AMPK signaling pathway significantly
      increased the expression level of IDE, and decreased the accumulation of Abeta40
      and Abeta42, as well as alleviated the spatial learning and recognition
      impairments.

PMID- 29222351
TI  - How are junior doctors managing patients with self-limiting illnesses at their
      first presentation? A video vignette study.
AB  - PURPOSE: To conduct a video vignette survey of medical students and doctors
      investigating test ordering for patients presenting with self-limiting or minor
      illness. METHODS: Participants were shown six video vignettes of common self
      limiting illnesses and invited to devise investigation and management plans for
      the patients' current presentation. The number of tests ordered was compared with
      those recommended by an expert panel. A Theory of Planned Behaviour Questionnaire
      explored participants' beliefs and attitudes about ordering tests in the context
      of self-limiting illness. RESULTS: Participants (n=61) were recruited from across
      Australia. All participants ordered at least one test that was not recommended by
      the experts in most cases. Presentations that focused mainly on symptoms (eg, in
      cases with bowel habit disturbance and fatigue) resulted in more tests being
      ordered. A test not recommended by experts was ordered on 54.9% of occasions.
      With regard to attitudes to test ordering, junior doctors were strongly
      influenced by social norms. The number of questionable tests ordered in this
      survey of 366 consultations has a projected cost of $17 000. CONCLUSIONS: This
      study suggests that there is some evidence of questionable test ordering by these
      participants with significant implications for costs to the health system.
      Further research is needed to explore the extent and reasons for test ordering by
      junior doctors across a range of clinical settings.

PMID- 29222353
TI  - CMS releases medication review performance data as part of Medicare Star ratings.

PMID- 29222352
TI  - Lack of information threatens ability to plan for drug shortages.

PMID- 29222354
TI  - Students help Medicare beneficiaries optimize their Part D benefit.

PMID- 29222355
TI  - Corrections.

PMID- 29222356
TI  - Corrections.

PMID- 29222357
TI  - Corrections.

PMID- 29222358
TI  - Leveraging precision medicine to mitigate medication-safety challenges.

PMID- 29222359
TI  - Pharmacy technician-administered vaccines in Idaho.

PMID- 29222360
TI  - Antiviral treatment of BK virus viremia after kidney transplantation.
AB  - PURPOSE: The various antiviral treatment options in the management of BK virus
      (BKV) viremia and BKV-associated nephropathy (BKVAN) are reviewed. SUMMARY:
      Review of the PubMed database from 1990 to 2016 for all English language case
      series, cohort studies, and randomized controlled trials detailing antiviral
      treatment of BKV viremia or BKVAN in kidney transplant recipients returned only
      16 published reports. The majority of these reports were based on small case
      series or protocol-based cohort studies, with no prospective head-to-head data
      and only modest benefit reported for cidofovir, leflunomide, i.v. immunoglobulin
      (IVIG), and fluoroquinolone therapy. Given the lack of comparative data,
      appropriate antiviral treatment of BKV viremia should be determined based on
      institutional immunosuppressive protocols and posttransplantation outcomes. In
      appropriate patients who are not immunologically sensitized, substituting
      leflunomide for mycophenolate as part of immunosuppression reduction is
      reasonable and may result in viral clearance in up to 43% of patients at 4 weeks.
      In patients with persistent viremia despite immunosuppression reduction, either
      IVIG 2 g/kg administered over 2-5 days or cidofovir 0.5 mg/kg per week until
      viral clearance is achieved is generally well tolerated. Otherwise, there is
      insufficient evidence to recommend the use of fluoroquinolone therapy in either
      the treatment or prophylaxis of BKV viremia at this time. CONCLUSION: A review of
      the published literature revealed that certain populations of patients with BKV
      viremia or BKVAN can benefit from cidofovir, leflunomide, and IVIG therapy, but
      these data were derived from case series or protocol-driven cohort studies.
      Providers should treat patients on an individual basis to maximize clinical
      effectiveness while limiting adverse reactions.

PMID- 29222361
TI  - Evaluation of opioid prescribing after rescheduling of hydrocodone-containing
      products.
AB  - PURPOSE: Institutional prescribing trends of hydrocodone-containing products
      (HCPs) before and after the Drug Enforcement Administration's rescheduling of
      HCPs were evaluated. METHODS: A retrospective evaluation was performed on 6 oral
      opioid analgesics on the hospital formulary that were prescribed to patients
      treated at Texas Children's Hospital and Pavilion for Women for the 6 months
      before and after the rescheduling of HCPs on October 6, 2014. Patients were
      eligible for inclusion if they were prescribed any of the following oral agents:
      HCPs (e.g., hydrocodone with acetaminophen), codeine-containing products (e.g.,
      codeine, codeine with acetaminophen), morphine, hydromorphone, oxycodone
      containing products (e.g., oxycodone, oxycodone with acetaminophen), and
      tramadol. RESULTS: During the 12-month study period, a total of 38,928 inpatient
      orders and outpatient prescriptions were processed for the studied agents in both
      locations; the majority were orders for inpatients. An overall reduction in the
      total number of opioid prescriptions was observed after the rescheduling of HCPs.
      Substantial increases in the proportional use of codeine were observed in all 4
      settings after HCP rescheduling. Data for each of the agents revealed a shift in
      prescribing patterns centered along the HCP rescheduling date of October 6, 2014,
      and revealed a decrease in HCP use across all areas with an accompanying increase
      in codeine-containing products, oxycodone-containing products, and tramadol.
      CONCLUSION: The rescheduling of HCPs resulted in a reduction in HCP prescriptions
      but was accompanied by increases in the use of codeine-containing products and
      tramadol in all settings.

PMID- 29222362
TI  - Randomized controlled evaluation of an insulin pen storage policy.
AB  - PURPOSE: Results of a quality-improvement project to enhance safeguards against
      "wrong-pen-to-patient" insulin pen errors by permitting secure bedside storage of
      insulin pens are reported. METHODS: A cluster-randomized controlled evaluation
      was conducted at an academic medical center to assess adherence with
      institutional policy on insulin pen storage before and after implementation of a
      revised policy allowing pen storage in locking boxes in patient rooms. In phase 1
      of the study, baseline data on policy adherence were captured for 8 patient care
      units (4 designated as intervention units and 4 designated as control units). In
      phase 2, policy adherence was assessed through direct observation during weekly
      audits after lock boxes were installed on intervention units and education on
      proper insulin pen storage was provided to nurses in all 8 units. RESULTS: Phase
      1 rates of adherence to insulin pen storage policy were 59% in the intervention
      units and 49% in the control units (p = 0.56). During phase 2, there was no
      significant change from baseline in control unit adherence (67%, p = 0.26), but
      adherence in intervention units improved significantly, to 89% (p = 0.005).
      Common types of observed nonadherence included pens being unsecured in patient
      rooms or nurses' pockets or left in patient-specific medication drawers after
      patient discharge. CONCLUSION: An institutional policy change permitting secure
      storage of insulin pens close to the point of care, paired with nurse education,
      increased adherence more than education alone.

PMID- 29222363
TI  - Stability of a pyrimethamine suspension compounded from bulk powder.
AB  - PURPOSE: Development of a stability-indicating high-performance liquid
      chromatography (HPLC) method for pyrimethamine analysis, with subsequent
      application of that method to assess the 90-day stability of a pyrimethamine
      suspension compounded from bulk USP-grade pyrimethamine powder, is described.
      METHODS: A stability-indicating method of HPLC with ultraviolet detection
      specific to pyrimethamine was developed according to pharmacopeial
      recommendations and validated. The method was applied to investigate the
      stability of a 2-mg/mL pyrimethamine suspension in a vehicle consisting of Ora
      Plus and Ora-Sweet (Perrigo) over a period of 90 days. Three replicate test
      preparations were stored at room temperature or refrigerated at 4.3-5.2  degrees
      C, and samples were analyzed in duplicate immediately after preparation and on
      study days 1, 2, 4, 7, 10, 14, 21, 30, 48, 60, 75, and 90. RESULTS: The 2-mg/mL
      suspension of pyrimethamine in Ora-Plus and Ora-Sweet retained 90-110% of the
      labeled potency to 90 days at both temperature ranges. However, color changes in
      the samples stored at room temperature observed at day 60 indicated that a beyond
      use date less than 90 days from the preparation date should be specified when the
      suspension is to be stored at room temperature. CONCLUSION: The study
      demonstrated that USP-grade pyrimethamine powder can be formulated as a 2-mg/mL
      suspension in a vehicle of Ora-Plus and Ora-Sweet and is stable when stored at
      room temperature and when refrigerated, in amber plastic bottles, for 48 and 90
      days, respectively.

PMID- 29222364
TI  - Investigating inpatient medication administration using the theory of planned
      behavior.
AB  - PURPOSE: Results of a study to determine behavioral factors that help explain why
      nurses often do not obtain and administer medications from automated dispensing
      cabinets (ADCs) "one patient at a time" are reported. METHODS: To investigate
      nurses' frequent failure to adhere to best-practice standards for ADC use, a 12
      item questionnaire developed using information obtained from an elicitation study
      and a focus group session was e-mailed to 755 nurses at an academic medical
      center. A model based on constructs of the theory of planned behavior (attitude,
      subjective norm, and perceived behavioral control) was used to evaluate nurses'
      intent to follow ADC best practices through univariate and multivariate analyses.
      RESULTS: Of the 755 nurses targeted in the survey, 271 (34%) submitted usable
      responses. A favorable attitude toward safe ADC dispensing practices and a
      supportive subjective norm were strongly associated with intent to use ADCs
      properly; those factors remained highly correlated with intent (p < 0.001 for
      both) after controlling for demographic and work-related variables such as years
      in practice and patient workload. Eighty percent of observed variability of
      intent was explained by the evaluated constructs and variables (p < 0.001),
      suggesting that direct interventions at the patient care unit level and peer
      influence would likely be effective in promoting safe ADC use. CONCLUSION: A
      survey based on the theory of planned behavior demonstrated that attitude and
      subjective norm were important independent predictors of nurse intent to use ADCs
      properly.

PMID- 29222365
TI  - Implementation of an integrated pharmacy supply management strategy.
AB  - PURPOSE: Implementation of an integrated pharmacy supply management strategy is
      described. SUMMARY: In 2011, the formulary approval process and supply management
      for oncology medications were independent of each other at an oncology infusion
      center. Numerous nonformulary medications were kept on hand and reordered based
      on inventory levels that were established with inadequate usage information,
      while some formulary agents did not have on-hand inventory levels and had to be
      reordered on a patient-specific basis, which required paperwork and then a review
      by drug information staff per institutional policy. Because there was no true
      distinction in the ordering of formulary versus nonformulary oncology agents, the
      medical staff prescribed both in the same manner, leaving the pharmacy staff
      responsible for ensuring that enough quantities were on hand for many drugs,
      regardless of formulary status. Using supply chain management principles, a
      formal analysis of the on-hand inventory was performed. In addition, the
      formulary process for oncology drugs was restructured to align with how oncology
      drugs are managed for on-hand inventory levels. The alignment of these processes
      allowed the operation to have 1 supply strategy for the ambulatory oncology
      infusion center. As a result, inventory exhaustion rates were reduced by 70% and
      inventory turn rates improved by 78%. There was also significant time savings in
      the operational process streamlining, eliminating the rework and inefficiencies
      caused by an unclear process that was not fully captured in this assessment.
      CONCLUSION: Alignment of the formulary review process with inventory analyses
      that support supply management principles reduced inventory exhaustion while
      improving inventory turn rates.

PMID- 29222369
TI  - Introduction: Standards of Medical Care in Diabetes-2018.

PMID- 29222368
TI  - Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting
      miR-29b.
AB  - Transforming growth factor-beta/Smad signaling plays an important role in
      diabetic nephropathy. The current study identified a novel Smad3-dependent long
      noncoding RNA (lncRNA) Erbb4-IR in the development of type 2 diabetic nephropathy
      (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of
      db/db mice and specifically induced by advanced glycosylation end products (AGEs)
      via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was
      revealed by kidney-specific silencing of Erbb4-IR to protect against the
      development of T2DN, such as elevated microalbuminuria, serum creatinine, and
      progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and
      IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells
      (mTECs). Mechanistically, we identified that the Erbb4-IR-microRNA (miR)-29b axis
      was a key mechanism of T2DN because Erbb4-IR was able to bind the 3' untranslated
      region of miR-29b genomic sequence to suppress miR-29b expression at
      transcriptional level. In contrast, silencing of renal Erbb4-IR increased miR-29b
      and therefore protected the kidney from progressive renal injury in db/db mice
      and prevented mTECs and mMCs from AGE-induced loss of miR-29b and fibrotic
      response in vitro. Collectively, we identify that Erbb4-IR is a Smad3-dependent
      lncRNA that promotes renal fibrosis in T2DN by suppressing miR-29b. Targeting
      Erbb4-IR may represent a novel therapy for T2DN.

PMID- 29222370
TI  - Professional Practice Committee: Standards of Medical Care in Diabetes-2018.

PMID- 29222371
TI  - Summary of Revisions: Standards of Medical Care in Diabetes-2018.

PMID- 29222372
TI  - 1. Improving Care and Promoting Health in Populations: Standards of Medical Care
      in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multi-disciplinary expert committee, are responsible for updating
      the Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/content/clinical-practice
      recommendations.

PMID- 29222373
TI  - 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in
      Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222374
TI  - 3. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of
      Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222375
TI  - 4. Lifestyle Management: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222376
TI  - 5. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes
      2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222377
TI  - 6. Glycemic Targets: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222378
TI  - 7. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical
      Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222379
TI  - 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in
      Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222380
TI  - 9. Cardiovascular Disease and Risk Management: Standards of Medical Care in
      Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222381
TI  - 10. Microvascular Complications and Foot Care: Standards of Medical Care in
      Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222382
TI  - 11. Older Adults: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222383
TI  - 12. Children and Adolescents: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222384
TI  - 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes
      2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222385
TI  - 14. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222387
TI  - Professional Practice Committee, American College of Cardiology-Designated
      Representatives, and American Diabetes Association Staff Disclosures.

PMID- 29222386
TI  - 15. Diabetes Advocacy: Standards of Medical Care in Diabetes-2018.
AB  - The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes"
      includes ADA's current clinical practice recommendations and is intended to
      provide the components of diabetes care, general treatment goals and guidelines,
      and tools to evaluate quality of care. Members of the ADA Professional Practice
      Committee, a multidisciplinary expert committee, are responsible for updating the
      Standards of Care annually, or more frequently as warranted. For a detailed
      description of ADA standards, statements, and reports, as well as the evidence
      grading system for ADA's clinical practice recommendations, please refer to the
      Standards of Care Introduction Readers who wish to comment on the Standards of
      Care are invited to do so at professional.diabetes.org/SOC.

PMID- 29222389
TI  - Natural killer cells and T lymphocytes in pregnancy and pre-eclampsia.
AB  - Although pre-eclampsia (PE), a hypertensive disorder of pregnancy, has
      significant maternal and fetal morbidity and mortality worldwide, the mechanisms
      contributing to this disease have not been fully elucidated. Studies in patients
      and experimental models have shown that changes in the number or function of
      immune cells of both the adaptive and innate immune systems contribute to the
      development and pathogenesis of PE. This commentary summarizes our current
      understanding of the role of the immune system in the pathogenesis of PE,
      specifically focussing on dysfunction of natural killer (NK) cells and T
      lymphocyte populations.

PMID- 29222390
TI  - Sodium Channel Remodeling in Subcellular Microdomains of Murine Failing
      Cardiomyocytes.
AB  - BACKGROUND: Cardiac sodium channel (NaV1.5) dysfunction contributes to
      arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to
      distinct subcellular microdomains within the cardiomyocyte, where it associates
      with region-specific proteins, yielding complexes whose function is location
      specific. We herein investigated sodium channel remodeling within distinct
      cardiomyocyte microdomains during heart failure. METHODS AND RESULTS: Mice were
      subjected to 6 weeks of transverse aortic constriction (TAC; n=32) to induce
      heart failure. Sham-operated on mice were used as controls (n=20). TAC led to
      reduced left ventricular ejection fraction, QRS prolongation, increased heart
      mass, and upregulation of prohypertrophic genes. Whole-cell sodium current (INa)
      density was decreased by 30% in TAC versus sham-operated on cardiomyocytes. On
      macropatch analysis, INa in TAC cardiomyocytes was reduced by 50% at the lateral
      membrane (LM) and by 40% at the intercalated disc. Electron microscopy and
      scanning ion conductance microscopy revealed remodeling of the intercalated disc
      (replacement of [inter-]plicate regions by large foldings) and LM (less
      identifiable T tubules and reduced Z-groove ratios). Using scanning ion
      conductance microscopy, cell-attached recordings in LM subdomains revealed
      decreased INa and increased late openings specifically at the crest of TAC
      cardiomyocytes, but not in groove/T tubules. Failing cardiomyocytes displayed a
      denser, but more stable, microtubule network (demonstrated by increased alpha
      tubulin and Glu-tubulin expression). Superresolution microscopy showed reduced
      average NaV1.5 cluster size at the LM of TAC cells, in line with reduced INa.
      CONCLUSIONS: Heart failure induces structural remodeling of the intercalated
      disc, LM, and microtubule network in cardiomyocytes. These adaptations are
      accompanied by alterations in NaV1.5 clustering and INa within distinct
      subcellular microdomains of failing cardiomyocytes.

PMID- 29222392
TI  - Case-control study to assess the association between colorectal cancer and
      selected occupational agents using INTEROCC job exposure matrix.
AB  - BACKGROUND: Colorectal cancer is the third most prevalent cancer in the world and
      is twice as common in developed countries when compared with low-income and
      middle-income countries. Few occupational risk factors for colorectal cancer have
      been identified. This case-control study aimed to assess the association between
      colorectal cancer and occupational exposure to selected solvents, combustion
      products, metals, dusts and other agents. METHODS: Cases (n=918) were enrolled
      from the Western Australian Cancer Registry from June 2005 to August 2007.
      Controls (n=1021) were randomly selected from the Western Australian electoral
      roll. We collected lifetime occupational history from cases and controls, in
      addition to their demographic and lifestyle characteristics. We applied the
      INTEROCC job exposure matrix to convert the occupational history to occupational
      exposure for 18 selected agents. Three exposure indices were developed: (1)
      exposed versus non-exposed; (2) lifetime cumulative exposure; and (3) total
      duration of exposure. The associations between colorectal cancer and the selected
      agents were estimated using logistic regression models adjusting for sex and age.
      RESULTS: None of the 18 selected agents showed an association with colorectal
      cancer. No dose-response relationships with lifetime cumulative exposure or
      duration of exposure were observed. CONCLUSION: There was no evidence to suggest
      that occupational exposure to 18 selected agents increased the risk of colorectal
      cancer.

PMID- 29222391
TI  - The G protein-coupled receptor Gpr161 regulates forelimb formation, limb
      patterning and skeletal morphogenesis in a primary cilium-dependent manner.
AB  - The role of basal suppression of the sonic hedgehog (Shh) pathway and its
      interaction with Indian hedgehog (Ihh) signaling during limb/skeletal
      morphogenesis is not well understood. The orphan G protein-coupled receptor
      Gpr161 localizes to primary cilia and functions as a negative regulator of Shh
      signaling by promoting Gli transcriptional repressor versus activator formation.
      Here, we show that forelimb buds are not formed in Gpr161 knockout mouse embryos
      despite establishment of prospective limb fields. Limb-specific deletion of
      Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent
      patterning defects resulting in polysyndactyly. In addition, endochondral bone
      formation in forearms, including formation of both trabecular bone and bone
      collar was prevented. Endochondral bone formation defects resulted from
      accumulation of proliferating round/periarticular-like chondrocytes, lack of
      differentiation into columnar chondrocytes, and corresponding absence of Ihh
      signaling. Gpr161 deficiency in craniofacial mesenchyme also prevented
      intramembranous bone formation in calvarium. Defects in limb patterning,
      endochondral and intramembranous skeletal morphogenesis were suppressed in the
      absence of cilia. Overall, Gpr161 promotes forelimb formation, regulates limb
      patterning, prevents periarticular chondrocyte proliferation and drives
      osteoblastogenesis in intramembranous bones in a cilium-dependent manner.

PMID- 29222393
TI  - PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration
      during stent retriever thrombectomy - evaluation of a double embolic protection
      approach in endovascular stroke treatment.
AB  - PURPOSE: Stent retriever-based mechanical thrombectomy (MT) for emergent large
      vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing
      distal embolization and embolization to new vascular territories. Well
      established embolic protection approaches include proximal flow arrest and distal
      aspiration techniques during stent retriever maneuvers. Aiming at the reduction
      of thrombus fragmentation during MT we evaluated a technical approach combining
      proximal balloon occlusion together with direct thrombus aspiration during MT:
      the PROTECT technique. METHODS: We performed a case-control study comparing the
      PROTECT technique with sole distal aspiration during MT regarding technical and
      procedural parameters, n=200 patients with ELVO of either the terminus of the
      internal carotid artery or the proximal middle artery were included. RESULTS:
      PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher
      rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of
      complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration
      during MT. CONCLUSION: The PROTECT technique is a promising new approach to
      significantly reduce thrombus fragmentation and, hence distal embolization during
      MT. This safe and efficient technique needs to be validated in larger trials to
      confirm our results.

PMID- 29222394
TI  - Equivalent favorable outcomes possible after thrombectomy for posterior
      circulation large vessel occlusion compared with the anterior circulation: the
      MUSC experience.
AB  - INTRODUCTION: In acute ischemic stroke (AIS), posterior circulation large vessel
      occlusions (LVOs) have been associated with poorer outcomes compared with
      anterior circulation LVOs. The outcomes of anterior versus posterior circulation
      thrombectomy for LVOs were compared at a high volume center employing a direct
      aspiration first pass technique (ADAPT). METHODS: We retrospectively studied a
      database of AIS cases that underwent ADAPT thrombectomy for LVOs. Cases were
      grouped by anatomical location of thrombectomy (posterior vs anterior
      circulation), and analysis was performed on both entire sample size. RESULTS: A
      total of 436 AIS patients (50.2% women, mean age 67.3 years) underwent ADAPT
      thrombectomy for LVO during the study period, of whom 13% of had posterior
      circulation thrombectomy. Patients with posterior circulation thrombectomy did
      not show a significant difference in preprocedural variables, including age,
      baseline National Institutes of Health Stroke Scale (NIHSS), and onset to groin
      time, compared with anterior circulation (P>0.05). There were also no differences
      in procedural variables between the two groups. Patients in the posterior group
      were found to have a similar likelihood of good outcome (modified Rankin Scale
      score 0-2) at 90 days compared with the anterior group (42.9% vs 43.2%,
      respectively), and a small but not significant increase in mortality at 90 days.
      Multilogistic regression analysis showed that the anatomical location (anterior
      vs posterior) was not an independent predictor of good outcome or mortality after
      thrombectomy. Prominent predictors of outcome/mortality included age, female
      gender, procedure time, and baseline NIHSS. CONCLUSIONS: Our findings demonstrate
      that when patients are carefully selected for thrombectomy, those with posterior
      circulation LVOs can achieve similar outcomes compared with anterior circulation
      thrombectomy, indicating comparable safety and efficacy profiles.

PMID- 29222396
TI  - Insights into the Regulation of Collecting Duct Homeostasis by Small Noncoding
      RNAs.

PMID- 29222395
TI  - Extracellular Adenosine Stimulates Vacuolar ATPase-Dependent Proton Secretion in
      Medullary Intercalated Cells.
AB  - Acidosis is an important complication of AKI and CKD. Renal intercalated cells
      (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are
      extensively involved in acid-base homeostasis. H+ secretion in type A
      intercalated cells (A-ICs) is regulated by apical vesicle recycling and
      stimulated by cAMP. In other cell types, cAMP is increased by extracellular
      agonists, including adenosine, through purinergic receptors. Adenosine is a Food
      and Drug Administration-approved drug, but very little is known about the effect
      of adenosine on IC function. Therefore, we investigated the role of adenosine in
      the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine
      or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase
      apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or
      other IC subtypes. Both receptors are located in A-IC apical membranes, and
      adenosine injection increased urine adenosine concentration and decreased urine
      pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist
      induced V-ATPase translocation from vesicles to the plasma membrane and increased
      protein kinase A (PKA)-dependent protein phosphorylation in purified medullary
      ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the
      PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed
      that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that
      medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B
      receptors in a cAMP/PKA pathway-dependent mechanism to induce V-ATPase-dependent
      H+ secretion.

PMID- 29222397
TI  - Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through
      Aryl Hydrocarbon Receptor Signaling.
AB  - In patients with CKD, not only renal but also, nonrenal clearance of drugs is
      altered. Uremic toxins could modify the expression and/or activity of drug
      transporters in the liver. We tested whether the uremic toxin indoxyl sulfate
      (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor,
      could change the expression of the following liver transporters involved in drug
      clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1,
      ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2 We showed that IS increases the
      expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded
      by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the
      other transporters. This effect depended on the aryl hydrocarbon receptor
      pathway. Presence of human albumin at physiologic concentration in the culture
      medium did not abolish the effect of IS. In two mouse models of CKD, the decline
      in renal function associated with the accumulation of IS in serum and the
      specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or
      kidney transplant recipients with CKD, those with higher serum levels of IS
      needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin
      target blood concentration. This need associated with serum levels of IS
      independent of renal function. These findings suggest that increased activity of
      P-gp could be responsible for increased hepatic cyclosporin clearance.
      Altogether, these results suggest that uremic toxins, such as IS, through effects
      on drug transporters, may modify the nonrenal clearance of drugs in patients with
      CKD.

PMID- 29222398
TI  - Cerebral Palsy in Extremely Preterm Infants.
AB  - BACKGROUND AND OBJECTIVES: The risk of cerebral palsy (CP) is high in preterm
      infants and is often accompanied by additional neurodevelopmental comorbidities.
      The present study describes lifetime prevalence of CP in a population-based
      prospective cohort of children born extremely preterm, including the type and
      severity of CP and other comorbidities (ie, developmental delay and/or cognitive
      impairment, neurobehavioral morbidity, epilepsy, vision and hearing impairments),
      and overall severity of disability. In this study, we also evaluate whether age
      at assessment, overall severity of disability, and available sources of
      information influence outcome results. METHODS: All Swedish children born before
      27 weeks' gestation from 2004 to 2007 were included (the Extremely Preterm
      Infants in Sweden Study). The combination of neonatal information, information
      from clinical examinations and neuropsychological assessments at 2.5 and 6.5
      years of age, original medical chart reviews, and extended chart reviews was
      used. RESULTS: The outcome was identified in 467 (94.5%) of eligible children
      alive at 1 year of age. Forty-nine (10.5%) children had a lifetime diagnosis of
      CP, and 37 (76%) were ambulatory. Fourteen (29%) had CP diagnosed after 2.5 years
      of age, 37 (76%) had at least 1 additional comorbidity, and 27 (55%) had severe
      disability. The probability for an incomplete evaluation was higher in children
      with CP compared with children without CP. CONCLUSIONS: Children born extremely
      preterm with CP have various comorbidities and often overall severe disability.
      The importance of long-term follow-up and of obtaining comprehensive outcome
      information from several sources in children with disabilities is shown.

PMID- 29222400
TI  - NKG2D-Based CAR T Cells and Radiotherapy Exert Synergistic Efficacy in
      Glioblastoma.
AB  - Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy
      against several malignancies including glioblastoma, the most common and most
      aggressive malignant primary brain tumor in adults. The challenges in solid tumor
      immunotherapy comprise heterogenously expressed tumor target antigens and
      restricted trafficking of CAR T cells to and impaired long-term persistence at
      the tumor site, as well as the unaddressed integration of CAR T-cell therapy into
      conventional anticancer treatments. We addressed these questions using a NKG2D
      based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent
      orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFNgamma
      production and cytolytic activity in vitro Upon systemic administration in vivo,
      chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse
      events, prolonged survival, and cured a fraction of glioma-bearing mice.
      Surviving mice were protected long-term against tumor rechallenge.
      Mechanistically, this was not solely the result of a classical immune memory
      response, but rather involved local persistence of chNKG2D T cells. A
      subtherapeutic dose of local radiotherapy in combination with chNKG2D T-cell
      treatment resulted in synergistic activity in two independent syngeneic mouse
      glioma models by promoting migration of CAR T cells to the tumor site and
      increased effector functions. We thus provide preclinical proof-of-concept of
      NKG2D CAR T-cell activity in mouse glioma models and demonstrate efficacy, long
      term persistence, and synergistic activity in combination with radiotherapy,
      providing a rationale to translate this immunotherapeutic strategy to human
      glioma patients.Significance: These findings provide evidence for synergy of
      conventional anticancer therapy and CAR T cells and heralds future studies for
      other treatment combinations. Cancer Res; 78(4); 1031-43. (c)2017 AACR.

PMID- 29222401
TI  - Genetics of Floral Development (By Christine Fleet).
AB  - Summaryplantcell;29/11/tpc.117.tt1117/FIG1F1fig1A basic model for floral organ
      identity has been developed using model systems such as Arabidopsis thaliana,
      snapdragon (Antirrhinum majus), and petunia (Petunia hybrida). In this model,
      different combinations of proteins known as ABCDE proteins, mostly MADS-domain
      transcription factors, activate the transcription of target genes to specify the
      identity of each whorl of floral organs. Changes in the regulation or activation
      of these target genes contribute to the wide variety of floral forms that we see
      within and across species. In addition, duplications and divergence of these
      genes in different groups of flowering plants have resulted in differences in
      gene function and expression patterns, contributing to differences in flower form
      across species. Posted December 8, 2017.Click HERE to access Teaching Tool
      Components.

PMID- 29222399
TI  - Pediatric Disorders of Orthostatic Intolerance.
AB  - Orthostatic intolerance (OI), having difficulty tolerating an upright posture
      because of symptoms or signs that abate when returned to supine, is common in
      pediatrics. For example, ~40% of people faint during their lives, half of whom
      faint during adolescence, and the peak age for first faint is 15 years. Because
      of this, we describe the most common forms of OI in pediatrics and distinguish
      between chronic and acute OI. These common forms of OI include initial
      orthostatic hypotension (which is a frequently seen benign condition in
      youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic),
      vasovagal syncope, and postural tachycardia syndrome. We also describe the
      influences of chronic bed rest and rapid weight loss as aggravating factors and
      causes of OI. Presenting signs and symptoms are discussed as well as patient
      evaluation and testing modalities. Putative causes of OI, such as gravitational
      and exercise deconditioning, immune-mediated disease, mast cell activation, and
      central hypovolemia, are described as well as frequent comorbidities, such as
      joint hypermobility, anxiety, and gastrointestinal issues. The medical management
      of OI is considered, which includes both nonpharmacologic and pharmacologic
      approaches. Finally, we discuss the prognosis and long-term implications of OI
      and indicate future directions for research and patient management.

PMID- 29222402
TI  - ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in
      Developing Vestibular Hair Cells.
AB  - Sensory hair cells require control of physical properties of their apical plasma
      membranes for normal development and function. Members of the ADP-ribosylation
      factor (ARF) small GTPase family regulate membrane trafficking and cytoskeletal
      assembly in many cells. We identified ELMO domain-containing protein 1 (ELMOD1),
      a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the
      most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control
      of trafficking, we analyzed mice of both sexes from a strain lacking functional
      ELMOD1 [roundabout (rda)]. In rda/rda mice, cuticular plates of utricle hair
      cells initially formed normally, then degenerated after postnatal day 5; large
      numbers of vesicles invaded the compromised cuticular plate. Hair bundles
      initially developed normally, but the cell's apical membrane lifted away from the
      cuticular plate, and stereocilia elongated and fused. Membrane trafficking in
      type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice.
      Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was
      significantly elevated in rda/rda utricles compared with controls, and the level
      of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These
      results suggest that conversion of ARF6 to its GDP-bound form is necessary for
      final stabilization of the hair bundle.SIGNIFICANCE STATEMENT Assembly of the
      mechanically sensitive hair bundle of sensory hair cells requires growth and
      reorganization of apical actin and membrane structures. Hair bundles and apical
      membranes in mice with mutations in the Elmod1 gene degenerate after formation,
      suggesting that the ELMOD1 protein stabilizes these structures. We show that
      ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding
      protein ARF6, known to participate in actin assembly and membrane trafficking. We
      propose that conversion of ARF6 into the GDP-bound form in the apical domain of
      hair cells is essential for stabilizing apical actin structures like the hair
      bundle and ensuring that the apical membrane forms appropriately around the
      stereocilia.

PMID- 29222403
TI  - Common Pathophysiology in Multiple Mouse Models of Pitt-Hopkins Syndrome.
AB  - Mutations or deletions of the transcription factor TCF4 are linked to Pitt
      Hopkins syndrome (PTHS) and schizophrenia, suggesting that the precise pathogenic
      mutations dictate cellular, synaptic, and behavioral consequences. Here, we
      generated two novel mouse models of PTHS, one that mimics the most common
      pathogenic TCF4 point mutation (human R580W, mouse R579W) and one that deletes
      three pathogenic arginines, and explored phenotypes of these lines alongside
      models of pan-cellular or CNS-specific heterozygous Tcf4 disruption. We used mice
      of both sexes to show that impaired Tcf4 function results in consistent
      microcephaly, hyperactivity, reduced anxiety, and deficient spatial learning. All
      four PTHS mouse models demonstrated exaggerated hippocampal long-term
      potentiation (LTP), consistent with deficits in hippocampus-mediated behaviors.
      We further examined R579W mutant mice and mice with pan-cellular Tcf4
      heterozygosity and found that they exhibited hippocampal NMDA receptor
      hyperfunction, which likely drives the enhanced LTP. Together, our data pinpoint
      convergent neurobiological features in PTHS mouse models and provide a foundation
      for preclinical studies and a rationale for testing whether NMDAR antagonists
      might be used to treat PTHS.SIGNIFICANCE STATEMENT Pitt-Hopkins syndrome (PTHS)
      is a rare neurodevelopmental disorder associated with TCF4 mutations/deletions.
      Despite this genetic insight, there is a need to identify the function of TCF4 in
      the brain. Toward this goal, we developed two mouse lines, including one
      harboring the most prevalent pathogenic point mutation, and compared them with
      two existing models that conditionally delete Tcf4 Our data identify a set of
      overlapping phenotypes that may serve as outcome measures for preclinical studies
      of PTHS treatments. We also discovered penetrant enhanced synaptic plasticity
      across mouse models that may be linked to increased NMDA receptor function. These
      data reveal convergent neurobiological characteristics of PTHS mouse models and
      support the further investigation of NMDA receptor antagonists as a possible PTHS
      treatment.

PMID- 29222404
TI  - Lack of Parkin Anticipates the Phenotype and Affects Mitochondrial Morphology and
      mtDNA Levels in a Mouse Model of Parkinson's Disease.
AB  - PARK2 is the most common gene mutated in monogenic recessive familial cases of
      Parkinson's disease (PD). Pathogenic mutations cause a loss of function of the
      encoded protein Parkin. ParkinKO mice, however, poorly represent human PD
      symptoms as they only exhibit mild motor phenotypes, minor dopamine metabolism
      abnormalities, and no signs of dopaminergic neurodegeneration. Parkin has been
      shown to participate in mitochondrial turnover, by targeting damaged mitochondria
      with low membrane potential to mitophagy. We studied the role of Parkin on
      mitochondrial quality control in vivo by knocking out Parkin in the PD-mito-PstI
      mouse (males), where the mitochondrial DNA (mtDNA) undergoes double-strand breaks
      only in dopaminergic neurons. The lack of Parkin promoted earlier onset of
      dopaminergic neurodegeneration and motor defects in the PD-mito-PstI mice, but it
      did not worsen the pathology. The lack of Parkin affected mitochondrial
      morphology in dopaminergic axons and was associated with an increase in mtDNA
      levels (mutant and wild type). Unexpectedly, it did not cause a parallel increase
      in mitochondrial mass or mitophagy. Our results suggest that Parkin affects mtDNA
      levels in a mitophagy-independent manner.SIGNIFICANCE STATEMENT Parkinson's
      disease is characterized by progressive motor symptoms due to the selective loss
      of dopaminergic neurons in the substantia nigra. Loss-of-function mutations of
      Parkin cause some monogenic forms of Parkinson's disease, possibly through its
      role in mitochondrial turnover and quality control. To study whether Parkin has a
      role in vivo in the context of mitochondrial damage, we knocked out Parkin in a
      mouse model in which the mitochondrial DNA is damaged in dopaminergic neurons. We
      found that the loss of Parkin did not exacerbate the parkinsonian pathology
      already present in the mice, but it was associated with an increase in mtDNA
      levels (mutant and wild-type) without altering mitochondrial mass. These results
      shed new light on the function of Parkin in vivo.

PMID- 29222405
TI  - Multiple Weekly Dalbavancin Dosing for the Treatment of Native Vertebral
      Osteomyelitis Caused by Methicillin-Resistant Staphylococcus Aureus: A Case
      Report.
AB  - BACKGROUND Native vertebral osteomyelitis (NVO) is a common form of hematogenous
      osteomyelitis, with Staphylococcus aureus (S. aureus) being the most commonly
      isolated organism. Dalbavancin is approved by the US Food and Drug Administration
      (FDA) for the treatment of acute bacterial skin and skin structure infections
      (ABSSSI) and has a sufficiently promising pharmacokinetic and pharmacodynamic
      profile to be considered for the treatment of vertebral osteomyelitis. We
      describe here what is probably the first reported case of using multiple weekly
      dalbavancin to treat a complicated methicillin-resistant Staphylococcus aureus
      (MRSA) bacteremia and vertebral osteomyelitis. CASE REPORT A 58-year-old man with
      a long history of recurrent MRSA bacteremia, who failed multiple courses of
      vancomycin and daptomycin, presented with recurrent MRSA bacteremia complicated
      by diskitis and osteomyelitis of the lumbar vertebrae. The patient was treated
      with dalbavancin 1000 mg intravenously weekly for two weeks followed by 500 mg
      weekly for six additional weeks. He improved clinically, his back pain resolved,
      and C-reactive protein (CRP) decreased to normal. Three months after the last
      dose of dalbavancin therapy, he underwent angiography for peripheral artery
      diseases, after which he developed a fever, mild leukocytosis, an elevated CRP,
      and the repeat blood cultures were positive for MRSA. No apparent adverse events
      were observed during dalbavancin therapy. CONCLUSIONS In this case, multiple
      weekly dalbavancin infusions appeared to be safe in the treatment of vertebral
      osteomyelitis caused by MRSA, but did not seem to prevent infection recurrence.
      However, reinfection with a new strain from the angiography catheter insertion is
      highly likely. Clinical studies are needed to further assess the safety and
      effectiveness of multiple weekly dalbavancin dosing in the management of
      vertebral osteomyelitis.

PMID- 29222406
TI  - DNA Methylation-Mediated Silencing of Regenerating Protein 1 Alpha (REG1A)
      Affects Gastric Cancer Prognosis.
AB  - BACKGROUND Gastric cancer (GC) is one of the most common cause of cancer-related
      deaths. The clinical trials still lack the effective methods to treat or monitor
      the disease progression. In this research, the biological function and the
      underlying molecular mechanism of regenerating protein 1 alpha (REG1A) in GC were
      investigated. MATERIAL AND METHODS Gene expression omnibus (GEO), KMplot datasets
      and GC tissue microarray (n=164) were used to analyze the expression of REG1A and
      related patient prognoses in GC. Transwell matrigel assay, flow cytometry
      analysis and CCK8 cell viability assay were performed to detect the biological
      functions of REG1A. Western blotting and real-time PCR were used to detect the
      REG1A expression and PI3K/Akt related signaling. RESULTS It was found that the
      expression of REG1A was significantly downregulated in GC and closely related
      with clinicopathological findings or patient prognoses. REG1A overexpression
      could suppress the invasion, cell viability and promote the apoptosis of GC
      cells. Moreover, we found that the epigenetic methylation suppressed the
      expression level of REG1A in GC, and REG1A overexpression could suppress the
      phosphorylation of Akt or GSK3beta signaling. CONCLUSIONS Taken together, REG1A
      regulates cell invasion, apoptosis and viability in GC through activating
      PI3K/Akt-GSK3beta signaling. REG1A may serve as a promising therapeutic strategy
      for GC.

PMID- 29222407
TI  - Ballistic geometric resistance resonances in a single surface of a topological
      insulator.
AB  - Transport in topological matter has shown a variety of novel phenomena over the
      past decade. Although numerous transport studies have been conducted on three
      dimensional topological insulators (TIs), study of ballistic motion and thus
      exploration of potential landscapes on a hundred nanometer scale is for the
      prevalent TI materials almost impossible due to their low carrier mobility.
      Therefore, it is unknown whether helical Dirac electrons in TIs, bound to
      interfaces between topologically distinct materials, can be manipulated on the
      nanometer scale by local gates or locally etched regions. Here we impose a
      submicron periodic potential onto a single surface of Dirac electrons in high
      mobility strained mercury telluride (HgTe), which is a strong TI. Pronounced
      geometric resistance resonances constitute the clear-cut observation of a
      ballistic effect in three-dimensional TIs.

PMID- 29222408
TI  - Brain insulin resistance impairs hippocampal synaptic plasticity and memory by
      increasing GluA1 palmitoylation through FoxO3a.
AB  - High-fat diet (HFD) and metabolic diseases cause detrimental effects on
      hippocampal synaptic plasticity, learning, and memory through molecular
      mechanisms still poorly understood. Here, we demonstrate that HFD increases
      palmitic acid deposition in the hippocampus and induces hippocampal insulin
      resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase
      zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper
      palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity
      dependent trafficking to the plasma membrane. Accordingly, AMPAR current
      amplitudes and, more importantly, their potentiation underlying synaptic
      plasticity were inhibited, as well as hippocampal-dependent memory. Hippocampus
      specific silencing of Zdhhc3 and, interestingly enough, intranasal injection of
      the palmitoyltransferase inhibitor, 2-bromopalmitate, counteract GluA1 hyper
      palmitoylation and restore synaptic plasticity and memory in HFD mice. Our data
      reveal a key role of FoxO3a/Zdhhc3/GluA1 axis in the HFD-dependent impairment of
      cognitive function and identify a novel mechanism underlying the cross talk
      between metabolic and cognitive disorders.

PMID- 29222409
TI  - Immune stealth-driven O2 serotype prevalence and potential for therapeutic
      antibodies against multidrug resistant Klebsiella pneumoniae.
AB  - Emerging multidrug-resistant bacteria are a challenge for modern medicine, but
      how these pathogens are so successful is not fully understood. Robust
      antibacterial vaccines have prevented and reduced resistance suggesting a pivotal
      role for immunity in deterring antibiotic resistance. Here, we show the increased
      prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all
      major drug resistance groups correlating with a paucity of anti-O2 antibodies in
      human B cell repertoires. We identify human monoclonal antibodies to O-antigens
      that are highly protective in mouse models of infection, even against heavily
      encapsulated strains. These antibodies, including a rare anti-O2 specific
      antibody, synergistically protect against drug-resistant strains in adjunctive
      therapy with meropenem, a standard-of-care antibiotic, confirming the importance
      of immune assistance in antibiotic therapy. These findings support an antibody
      based immunotherapeutic strategy even for highly resistant K. pneumoniae
      infections, and underscore the effect humoral immunity has on evolving drug
      resistance.

PMID- 29222410
TI  - Tuning the interactions between chiral plasmonic films and living cells.
AB  - Designing chiral materials to manipulate the biological activities of cells has
      been an important area not only in chemistry and material science, but also in
      cell biology and biomedicine. Here, we introduce monolayer plasmonic chiral Au
      nanoparticle (NP) films modified with L- or D-penicillamine (Pen) to be developed
      for cell growth, differentiation, and retrieval. The monolayer films display high
      chiroptical activity, with circular dichroism values of 3.5 mdeg at 550 nm and
      26.8 mdeg at 775 nm. The L-Pen-NP films accelerate cell proliferation, whereas
      the D -Pen-NP films have the opposite effect. Remote irradiation with light is
      chosen to noninvasively collect the cells. The results demonstrate that left
      circularly polarized light improves the efficiency of cell detachment up to 91.2%
      for L-Pen-NP films. These findings will facilitate the development of cell
      culture in biomedical application and help to understand natural homochirality.

PMID- 29222411
TI  - Scaling of Yu-Shiba-Rusinov energies in the weak-coupling Kondo regime.
AB  - The competition of the free-spin state of a paramagnetic impurity on a
      superconductor with its screened counterpart is characterized by the energy scale
      of Kondo screening compared to the superconducting pairing energy Delta. When the
      experimental temperature suppresses Kondo screening, but preserves
      superconductivity, i.e., when Delta/k B > T > T K (k B is Boltzmann's constant
      and T K the Kondo temperature), this description fails. Here, we explore this
      temperature range in a set of manganese phthalocyanine molecules decorated with
      ammonia on Pb(111). We show that these molecules suffice the required energy
      conditions by exhibiting weak-coupling Kondo resonances. We correlate the Yu
      Shiba-Rusinov bound states energy inside the superconducting gap with the
      intensity of the Kondo resonance. The observed correlation follows the
      expectations for a classical spin on a superconductor. This finding is important
      in view of many theoretical predictions using a classical spin model, in
      particular for the description of Majorana bound states in magnetic
      nanostructures on superconducting substrates.

PMID- 29222413
TI  - Advanced Sulfur-Silicon Full Cell Architecture for Lithium Ion Batteries.
AB  - Lithium-ion batteries are crucial to the future of energy storage. However, the
      energy density of current lithium-ion batteries is insufficient for future
      applications. Sulfur cathodes and silicon anodes have garnered a lot of attention
      in the field due their high capacity potential. Although recent developments in
      sulfur and silicon electrodes show exciting results in half cell formats, neither
      electrode can act as a lithium source when put together into a full cell format.
      Current methods toward incorporating lithium in sulfur-silicon full cells
      involves prelithiating silicon or using lithium sulfide. These methods however,
      complicate material processing and creates safety hazards. Herein, we present a
      novel full cell battery architecture that bypasses the issues associated with
      current methods. This battery architecture gradually integrates controlled
      amounts of pure lithium into the system by allowing lithium the access to
      external circuit. A high specific energy density of 350 Wh/kg after 250 cycles at
      C/10 was achieved using this method. This work should pave the way for future
      researches into sulfur-silicon full cells.

PMID- 29222412
TI  - Ancestral perinatal obesogen exposure results in a transgenerational thrifty
      phenotype in mice.
AB  - Ancestral environmental exposures to non-mutagenic agents can exert effects in
      unexposed descendants. This transgenerational inheritance has significant
      implications for understanding disease etiology. Here we show that exposure of F0
      mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation
      predisposes unexposed F4 male descendants to obesity when dietary fat is
      increased. Analyses of body fat, plasma hormone levels, and visceral white
      adipose tissue DNA methylome and transcriptome collectively indicate that the F4
      obesity is consistent with a leptin resistant, thrifty phenotype. Ancestral TBT
      exposure induces global changes in DNA methylation and altered expression of
      metabolism-relevant genes. Analysis of chromatin accessibility in F3 and F4 sperm
      reveals significant differences between control and TBT groups and significant
      similarities between F3 and F4 TBT groups that overlap with areas of differential
      methylation in F4 adipose tissue. Our data suggest that ancestral TBT exposure
      induces changes in chromatin organization transmissible through meiosis and
      mitosis.

PMID- 29222414
TI  - Structural Dynamics of the MscL C-terminal Domain.
AB  - The large conductance mechanosensitive channel (MscL), acts as an osmoprotective
      emergency valve in bacteria by opening a large, water-filled pore in response to
      changes in membrane tension. In its closed configuration, the last 36 residues at
      the C-terminus form a bundle of five alpha-helices co-linear with the five-fold
      axis of symmetry. Here, we examined the structural dynamics of the C-terminus of
      EcMscL using site-directed spin labelling electron paramagnetic resonance (SDSL
      EPR) spectroscopy. These experiments were complemented with computational
      modelling including molecular dynamics (MD) simulations and finite element (FE)
      modelling. Our results show that under physiological conditions, the C-terminus
      is indeed an alpha-helical bundle, located near the five-fold symmetry axis of
      the molecule. Both experiments and computational modelling demonstrate that only
      the top part of the C-terminal domain (from the residue A110 to E118) dissociates
      during the channel gating, while the rest of the C-terminus stays assembled. This
      result is consistent with the view that the C-terminus functions as a molecular
      sieve and stabilizer of the oligomeric MscL structure as previously suggested.

PMID- 29222415
TI  - Prediction of genomic breeding values using new computing strategies for the
      implementation of MixP.
AB  - MixP is an implementation that uses the Pareto principle to perform genomic
      prediction. This study was designed to develop two new computing strategies: one
      strategy for nonMCMC-based MixP (FMixP), and the other one for MCMC-based MixP
      (MMixP). The difference is that MMixP can estimate variances of SNP effects and
      the probability that a SNP has a large variance, but FMixP cannot. Simulated data
      from an international workshop and real data on large yellow croaker were used as
      the materials for the study. Four Bayesian methods, BayesA, BayesCpi, MMixP and
      FMixP, were used to compare the predictive results. The results show that
      BayesCpi, MMixP and FMixP perform better than BayesA for the simulated data, but
      all methods have very similar predictive abilities for the large yellow croaker.
      However, FMixP is computationally significantly faster than the MCMC-based
      methods. Our research may have a potential for the future applications in genomic
      prediction.

PMID- 29222416
TI  - Functional analysis of human intrafusal fiber innervation by human gamma
      motoneurons.
AB  - Investigation of neuromuscular deficits and diseases such as SMA, as well as for
      next generation prosthetics, utilizing in vitro phenotypic models would benefit
      from the development of a functional neuromuscular reflex arc. The neuromuscular
      reflex arc is the system that integrates the proprioceptive information for
      muscle length and activity (sensory afferent), to modify motoneuron output to
      achieve graded muscle contraction (actuation efferent). The sensory portion of
      the arc is composed of proprioceptive sensory neurons and the muscle spindle,
      which is embedded in the muscle tissue and composed of intrafusal fibers. The
      gamma motoneurons (gamma-MNs) that innervate these fibers regulate the intrafusal
      fiber's stretch so that they retain proper tension and sensitivity during muscle
      contraction or relaxation. This mechanism is in place to maintain the sensitivity
      of proprioception during dynamic muscle activity and to prevent muscular damage.
      In this study, a co-culture system was developed for innervation of intrafusal
      fibers by human gamma-MNs and demonstrated by morphological and
      immunocytochemical analysis, then validated by functional electrophysiological
      evaluation. This human-based fusimotor model and its incorporation into the
      reflex arc allows for a more accurate recapitulation of neuromuscular function
      for applications in disease investigations, drug discovery, prosthetic design and
      neuropathic pain investigations.

PMID- 29222417
TI  - Insulin in motion: The A6-A11 disulfide bond allosterically modulates structural
      transitions required for insulin activity.
AB  - The structural transitions required for insulin to activate its receptor and
      initiate regulation of glucose homeostasis are only partly understood. Here,
      using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin
      with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers
      (cis and trans). Remarkably, only the cis isomer displays full insulin potency,
      rapidly lowering blood glucose in mice (even under insulin-resistant conditions).
      It also posseses reduced mitogenic activity in vitro. Further biophysical,
      crystallographic and molecular-dynamics analyses reveal that the A6-A11 bond
      configuration directly affects the conformational flexibility of insulin A-chain
      N-terminal helix, dictating insulin's ability to engage its receptor. We reveal
      that in native insulin, contraction of the Calpha-Calpha distance of the flexible
      A6-A11 cystine allows the A-chain N-terminal helix to unwind to a conformation
      that allows receptor engagement. This motion is also permitted in the cis isomer,
      with its shorter Calpha-Calpha distance, but prevented in the extended trans
      analogue. These findings thus illuminate for the first time the allosteric role
      of the A6-A11 bond in mediating the transition of the hormone to an active
      conformation, significantly advancing our understanding of insulin action and
      opening up new avenues for the design of improved therapeutic analogues.

PMID- 29222419
TI  - Probenecid arrests the progression of pronounced clinical symptoms in a mouse
      model of multiple sclerosis.
AB  - While it has been established that Probenecid (PBN) prevents the onset of
      experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether
      it has any effect on already manifest EAE. The aim of this study was therefore to
      analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest
      clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or
      they were left untreated. The clinical symptoms were monitored daily.
      Inflammation, demyelination and oligodendrocyte numbers were determined in the
      spinal cord. We were able to demonstrate that PBN not only significantly
      prolonged survival but also prevented the progression of clinical symptoms in the
      EAE model of multiple sclerosis. In addition, we were able to show that PBN
      reduced inflammation, T cell infiltration and oligodendrocyte cell loss. PBN was
      previously shown to inhibit - among other targets - pannexin channels. As
      pannexin channels provide conduits for ATP, are associated with the inflammasome,
      and act as "find me-signals" in the process of apoptosis, inhibition of pannexins
      via PBN might contribute to the PBN-effects observed in this study. The
      beneficial and therapeutic effects of PBN in the context of EAE demonstrate an
      intriguing link between PBN and neuroinflammation, which might foster
      translational interest.

PMID- 29222418
TI  - HEB is required for the specification of fetal IL-17-producing gammadelta T
      cells.
AB  - IL-17-producing gammadelta T (gammadeltaT17) cells are critical components of the
      innate immune system. However, the gene networks that control their development
      are unclear. Here we show that HEB (HeLa E-box binding protein, encoded by Tcf12)
      is required for the generation of a newly defined subset of fetal-derived CD73-
      gammadeltaT17 cells. HEB is required in immature CD24+CD73- gammadelta T cells
      for the expression of Sox4, Sox13, and Rorc, and these genes are repressed by
      acute expression of the HEB antagonist Id3. HEB-deficiency also affects mature
      CD73+ gammadelta T cells, which are defective in RORgammat expression and IL-17
      production. Additionally, the fetal TCRgamma chain repertoire is altered, and
      peripheral Vgamma4 gammadelta T cells are mostly restricted to the IFNgamma
      producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB
      dependent pathways for the development of CD73+ and CD73- gammadeltaT17 cells,
      and provides mechanistic evidence for control of the gammadeltaT17 gene network
      by HEB.

PMID- 29222420
TI  - Effect of high pressure treatment and short term storage on changes in main
      volatile compounds of Chinese liquor.
AB  - Changes in main volatile compounds of Chinese liquor after high pressure (HP)
      treatment and following short term storage were investigated. 400 MPa-15 min &
      400 MPa-30 min were applied to young liquor. Results from gas chromatography (GC)
      analysis revealed decreasing trends in alcohols, aldehydes and ethyl acetate
      immediately after HP treatments, which was in consistent with those in natural
      aging process; but no significant change was found in acids. However, differences
      in main volatile compounds between young liquor and pressurized liquors
      disappeared after two to six months of storage. Principal component analysis
      (PCA) performed well in presenting overall differences among all liquor groups,
      which verified our previous findings in GC analysis. This research broadened the
      knowledge of HP processing on distilled alcoholic beverages and provided an
      alternative technique for liquor quality modification.

PMID- 29222421
TI  - The Transcriptomic Signature Of Disease Development And Progression Of
      Nonalcoholic Fatty Liver Disease.
AB  - A longitudinal molecular model of the development and progression of nonalcoholic
      fatty liver disease (NAFLD) over time is lacking. We have recently validated a
      high fat/sugar water-induced animal (an isogenic strain of C57BL/6 J:129S1/SvImJ
      mice) model of NAFLD that closely mimics most aspects of human disease. The
      hepatic transcriptome of such mice with fatty liver (8 weeks), steatohepatitis
      with early fibrosis (16-24 weeks) and advanced fibrosis (52 weeks) after
      initiation of the diet was evaluated and compared to mice on chow diet. Fatty
      liver development was associated with transcriptional activation of lipogenesis,
      FXR-RXR, PPAR-alpha mediated lipid oxidation and oxidative stress pathways. With
      progression to steatohepatitis, metabolic pathway activation persisted with
      additional activation of IL-1/inhibition of RXR, granulocyte diapedesis/adhesion,
      Fc macrophage activation, prothrombin activation and hepatic stellate cell
      activation. Progression to advanced fibrosis was associated with dampening of
      metabolic, oxidative stress and cell stress related pathway activation but with
      further Fc macrophage activation, cell death and turnover and activation of
      cancer-related networks. The molecular progression of NAFLD involves a metabolic
      perturbation which triggers subsequent cell stress and inflammation driving cell
      death and turnover. Over time, inflammation and fibrogenic pathways become
      dominant while in advanced disease an inflammatory-oncogenic profile dominates.

PMID- 29222422
TI  - Reconfigurable Yagi-Uda antenna based on a silicon reflector with a solid-state
      plasma.
AB  - This paper describes the fabrication and characterization of a reconfigurable
      Yagi-Uda antenna based on a silicon reflector with a solid-state plasma. The
      silicon reflector, composed of serially connected p-i-n diodes, forms a highly
      dense solid-state plasma by injecting electrons and holes into the intrinsic
      region. When this plasma silicon reflector is turned on, the front-realized gain
      of the antenna increases by more than 2 dBi beyond 5.3 GHz. To achieve the large
      gain increment, the structure of the antenna is carefully designed with the aid
      of semiconductor device simulation and antenna simulation. By using an aluminum
      nitride (AlN) substrate with high thermal conductivity, self-heating effects from
      the high forward current in the p-i-n diode are efficiently suppressed. By
      comparing the antenna simulation data and the measurement data, we estimated the
      conductivity of the plasma silicon reflector in the on-state to be between 104
      and 105 S/m. With these figures, silicon material with its technology is an
      attractive tunable material for a reconfigurable antenna, which has attracted
      substantial interest from many areas, such as internet of things (IoT)
      applications, wireless network security, cognitive radio, and mobile and
      satellite communications as well as from multiple-input-multiple-output (MIMO)
      systems.

PMID- 29222424
TI  - Structural insight into a CE15 esterase from the marine bacterial metagenome.
AB  - The family 15 carbohydrate esterase (CE15) MZ0003, which derives from a marine
      Arctic metagenome, has a broader substrate scope than other members of this
      family. Here we report the crystal structure of MZ0003, which reveals that
      residues comprising the catalytic triad differ from previously-characterized
      fungal homologs, and resolves three large loop regions that are unique to this
      bacterial sub-clade. The catalytic triad of the bacterial CE15, which includes
      Asp 332 as its third member, closely resembles that of family 1 carbohydrate
      esterases (CE1), despite the overall lower structural similarity with members of
      this family. Two of the three loop regions form a subdomain that deepens the
      active site pocket and includes several basic residues that contribute to the
      high positive charge surrounding the active site. Docking simulations predict
      specific interactions with the sugar moiety of glucuronic-acid substrates, and
      with aromatically-substituted derivatives that serve as model compounds for the
      lignin-carbohydrate complex of plant cell walls. Molecular dynamics simulations
      indicate considerable flexibility of the sub-domain in the substrate-bound form,
      suggesting plasticity to accommodate different substrates is possible. The
      findings from this first reported structure of a bacterial member of the CE15
      family provide insight into the basis of its broader substrate specificity.

PMID- 29222423
TI  - Voluntary modulation of mental effort investment: an fMRI study.
AB  - Mental effort is a common phenomenological construct deeply linked to volition
      and self-control. While it is often assumed that the amount of exertion invested
      in a task can be voluntarily regulated, the neural bases of such faculty and its
      behavioural effects are yet insufficiently understood. In this study, we
      investigated how the instructions to execute a demanding cognitive task either
      "with maximum exertion" or "as relaxed as possible" affected performance and
      brain activity. The maximum exertion condition, compared to relaxed execution,
      was associated with speeded motor responses without an accuracy trade-off, and an
      amplification of both task-related activations in dorsal frontoparietal and
      cerebellar regions, and task-related deactivations in default mode network (DMN)
      areas. Furthermore, the visual cue to engage maximum effort triggered an
      anticipatory widespread increase of activity in attentional, sensory and
      executive regions, with its peak in the brain stem reticular activating system.
      Across individuals, this surge of activity in the brain stem, but also in medial
      wall cortical regions projecting to the adrenal medulla, positively correlated
      with increases in heart rate, suggesting that the intention to willfully modulate
      invested effort involves mechanisms related to catecholaminergic transmission and
      a suppression of DMN activity in favor of externally-directed attentional
      processes.

PMID- 29222425
TI  - Polymorphisms in JMJD1C are associated with pubertal onset in boys and
      reproductive function in men.
AB  - JMJD1C, a member of the Jumonji-domain containing histone demethylases protein
      family, has been associated with levels of sex-hormone binding globulin (SHBG)
      and testosterone in men, and knock-out rodent models show age-dependent
      infertility. The objective of this study was to investigate whether single
      nucleotide polymorphisms (SNPs) nearby JMJD1C are associated with pubertal onset
      in boys and with male reproduction. 671 peri-pubertal boys, 1,027 young men, 315
      fertile men, and 252 infertile men were genotyped for two JMJD1C SNPs (rs7910927
      and rs10822184). rs7910927 and rs10822184 showed high linkage. Boys with the
      rs7910927 TT genotype entered puberty 3.6 months earlier than their peers (p =
      2.5 * 10-2). In young men, the number of T alleles was associated with decreased
      levels of SHBG, follicle-stimulating hormone (FSH), testosterone, and
      testosterone x luteinizing hormone, as well as increased levels of Inhibin B,
      Inhibin B/FSH ratio, and testis size. No significant associations with semen
      parameters were observed and the genotype distribution was comparable among
      fertile and infertile men. In conclusion, genetic variation in the vicinity of
      JMJD1C had a surprisingly large impact on the age at pubertal onset in boys as
      well as levels of reproductive hormones and testis size in men, emphasizing the
      relationship between JMJD1C and reproductive functions.

PMID- 29222427
TI  - Exceptional increase in the creep life of magnesium rare-earth alloys due to
      localized bond stiffening.
AB  - Several recent papers report spectacular, and unexpected, order of magnitude
      improvement in creep life of alloys upon adding small amounts of elements like
      zinc. This microalloying effect raises fundamental questions regarding creep
      deformation mechanisms. Here, using atomic-scale characterization and first
      principles calculations, we attribute the 600% increase in creep life in a
      prototypical Mg-rare earth (RE)-Zn alloy to multiple mechanisms caused by RE-Zn
      bonding-stabilization of a large volume fraction of strengthening precipitates on
      slip planes, increase in vacancy diffusion barrier, reduction in activated cross
      slip, and enhancement of covalent character and bond strength around Zn solutes
      along the c-axis of Mg. We report that increased vacancy diffusion barrier, which
      correlates with the observed 25% increase in interplanar bond stiffness,
      primarily enhances the high-temperature creep life. Thus, we demonstrate that an
      approach of local, randomized tailoring of bond stiffness via microalloying
      enhances creep performance of alloys.

PMID- 29222426
TI  - Surveillance of antibiotic resistance among common Clostridium difficile
      ribotypes in Hong Kong.
AB  - Incidence of Clostridium difficile infection (CDI) is rapidly increasing and it
      poses a major health burden globally. However, data regarding the epidemiology of
      CDI in Asia are limited. We aimed to characterize the antimicrobial
      susceptibility patterns of common ribotypes of toxigenic C. difficile in Hong
      Kong. Fifty-three PCR ribotypes were identified among 284 toxigenic C. difficile
      clinical isolates. The five most prevalent ribotypes were 002 (13%), 017 (12%),
      014 (10%), 012 (9.2%), and 020 (9.5%). All tested C. difficile strains remained
      susceptible to metronidazole, vancomycin, meropenem and piperacillin/tazobactam,
      but highly resistant to cephalosporins. Of the fluoroquinolones, highest
      resistance to ciprofloxacin was observed (99%), followed by levofloxacin (43%)
      and moxifloxacin (23%). The two newly emerged PCR ribotypes, 017 and 002,
      demonstrated high levels of co-resistance towards clindamycin, tetracycline,
      erythromycin and moxifloxacin. PCR ribotypes 017 and 002 with multi-drug
      resistance are rapidly emerging and continuous surveillance is important to
      monitor the epidemiology of C. difficile to prevent outbreaks of CDI.

PMID- 29222428
TI  - Spectroscopic identification of active sites for the oxygen evolution reaction on
      iron-cobalt oxides.
AB  - The emergence of disordered metal oxides as electrocatalysts for the oxygen
      evolution reaction and reports of amorphization of crystalline materials during
      electrocatalysis reveal a need for robust structural models for this class of
      materials. Here we apply a combination of low-temperature X-ray absorption
      spectroscopy and time-resolved in situ X-ray absorption spectroelectrochemistry
      to analyze the structure and electrochemical properties of a series of disordered
      iron-cobalt oxides. We identify a composition-dependent distribution of di-MU-oxo
      bridged cobalt-cobalt, di-MU-oxo bridged cobalt-iron and corner-sharing cobalt
      structural motifs in the composition series. Comparison of the structural model
      with (spectro)electrochemical data reveals relationships across the composition
      series that enable unprecedented assignment of voltammetric redox processes to
      specific structural motifs. We confirm that oxygen evolution occurs at two
      distinct reaction sites, di-MU-oxo bridged cobalt-cobalt and di-MU-oxo bridged
      iron-cobalt sites, and identify direct and indirect modes-of-action for iron ions
      in the mixed-metal compositions.

PMID- 29222429
TI  - Case report: ischemic priapism secondary to tinzaparin.
AB  - Low-molecular-weight heparin (LMWH) therapy has recently been proposed as a cause
      of ischemic priapism. The evidence, however, remains scarce, as there are very
      few published cases of LMWH-induced priapism to date. The implications of such
      events are significant as ischemic priapism is a medical emergency. In current
      clinical practice we are seeing a trend towards LMWH therapies replacing
      unfractionated heparin (UFH). As LMWH therapies continue to gain favor, we will
      potentially see more cases of LMWH-induced priapism. As such, consideration
      should be given to determine the underlying pathophysiology and incidence of LMWH
      induced priapism. Herein, we present the case of a 33-year-old male with priapism
      in the setting of tinzaparin treatment.

PMID- 29222430
TI  - Fisheries-independent surveys identify critical habitats for young scalloped
      hammerhead sharks (Sphyrna lewini) in the Rewa Delta, Fiji.
AB  - Sharp declines in numerous shark populations around the world have generated
      considerable interest in better understanding and characterising their biology,
      ecology and critical habitats. The scalloped hammerhead shark (SHS, Sphyrna
      lewini) is subject to a multitude of natural and anthropogenic threats that are
      often exacerbated within the coastal embayments and estuaries used during SHS
      early life stages. In this study, we describe the temporal and spatial
      distribution, age class composition, and reproductive biology of SHS in the Rewa
      Delta (RD), Fiji. A total of 1054 SHS (including 796 tagged individuals; 101 of
      which were recaptured) were captured from September 2014 to March 2016 in the RD.
      A majority of the captures in this area were neonates and young-of-the-year (YOY)
      (99.8%). Significant seasonality in patterns of occurrence of both neonates and
      YOY individuals suggests a defined parturition period during the austral summer.
      Between the seven sampling sites in the RD we also found significant differences
      in SHS neonate catch per unit of effort, and average total length of individuals.
      According to the data, the RD is likely to represent an important nursery area
      for SHS up to one year of age.

PMID- 29222431
TI  - Utilization of blood by-products: An in silico and experimental combined study
      for BSA usage.
AB  - In order to exploit industrial discards, protein enzymatic hydrolysis is a
      currently popular methodology for obtaining bioactive peptides. However, once
      released, most promising peptides have to be selected from the mixture. In this
      work, the suitability of pepsin (EC 3.4.23.1) to hydrolyse serum albumin in order
      to obtain bioactive peptides was assessed. Then, a suitable process to obtain
      best separation of bioactive peptides was evaluated, using polyethersulfone
      membranes at different pH values. Serum albumin was easily hydrolysed by pepsin,
      reaching a DH value of the 65.64 +/- 1.57% of the maximum possible. A 23.25% of
      the identified peptides possessed high bioactivity scores (greater than 0.5), and
      one of them had reported bioactivity (LLL). Charge mechanisms always predominated
      over the sieve effect, and best transmission was accomplished at pH values close
      to the peptides isoelectric points. Basic and neutral peptides with the highest
      scores were always the most transmitted. Membrane material had greater influence
      than NMWCO in determining peptide transmission. In order to obtain purified
      fractions rich in peptides with high bioactivity scores from serum albumin,
      polyethersulfone membranes (applicable to industrial scale) of 5 kDa MWCO should
      be used at basic pH values after pepsin digestion.

PMID- 29222432
TI  - Genetic Variants of the Receptor for Advanced Glycation End-products in
      Susceptibility to Type 2 Diabetes Mellitus in Primary Hypertensive Patients.
AB  - Diabetes mellitus is frequently comorbid with hypertension, which is
      approximately twice as common as diabetes mellitus in China. We designed a case
      control association study to inspect the susceptibility of the receptor for
      advanced glycation end-products (RAGE) gene 6 variants to type 2 diabetes
      mellitus (T2DM) in 2199 patients with primary hypertension (1252 diabetic cases
      and 947 nondiabetic controls). The genotypes/alleles of -429T > C and 82Gly > Ser
      variants differed significantly between the two groups, and their associations
      with T2DM were significant after Bonferroni correction. Two variants, -374T > A
      and I/D, showed only marginal associations with T2DM. Haplotype analysis of above
      4 significant variants indicated that a low-penetrance haplotype simultaneously
      bearing -429C and 82Ser alleles was overrepresented in cases relative to controls
      (4.75% vs. 1.72%, P < 0.001). Moreover, the predictive capability of 6 variants
      was significantly superior to available risk factors, with better goodness-of
      fit. A predictive nomogram of 4 baseline risk factors and 2 variants of
      statistical significance was structured, with a good predictive accuracy (C-index
      = 0.761, P < 0.001). Taken together, our findings highlighted a contributory role
      of the RAGE gene, especially its two functional variants -429T > C and 82Gly >
      Ser, in susceptibility to T2DM in primary hypertensive patients, which may aid
      early detection and risk assessment for high-risk individuals.

PMID- 29222433
TI  - The evolution of phenotypic plasticity under global change.
AB  - Marine ecosystems are currently in a state of flux, with ocean warming and
      acidification occurring at unprecedented rates. Phenotypic plasticity underpins
      acclimatory responses by shifting the mean phenotype in a population, which may
      buffer the negative effects of global change. However, little is known about how
      phenotypic plasticity evolves across multiple generations. We tested this by
      reciprocally-transplanting the polychaete Ophryotrocha labronica between control
      and global change scenarios (ocean warming and acidification in isolation and
      combined) over five generations. By comparing the reaction norms of four life
      history traits across generations, we show that juvenile developmental rate in
      the combined scenario was the only trait that changed its plastic response across
      generations when transplanted back to control conditions, and that adaptive
      plasticity was conserved in most traits, despite significant levels of selection
      and strong declines in individual fitness in the multi-generational exposure. We
      suggest the change in level of plasticity in the combined scenario is caused by
      differential allocation of energy between the mean and the plasticity of the
      trait along the multigenerational exposure. The ability to maintain within
      generational levels of plasticity under global change scenarios has important eco
      evolutionary and conservation implications, which are examined under the
      framework of assisted evolution programs.

PMID- 29222434
TI  - Embryonic lethality and defective male germ cell development in mice lacking
      UTF1.
AB  - The germ cell lineage is specified early in embryogenesis and undergoes complex
      developmental programs to generate gametes. Here, we conducted genetic studies to
      investigate the role of Utf1 (Undifferentiated embryonic cell transcription
      factor 1) in mouse germ cell development. Utf1 is expressed in pluripotent
      embryonic stem (ES) cells and regulates ES cell differentiation. In a proteomics
      screen, we identified UTF1 among 38 proteins including DNMT3L and DND1 that
      associate with chromatin in embryonic testes. We find that UTF1 is expressed in
      embryonic and newborn gonocytes and in a subset of early spermatogonia.
      Ubiquitous inactivation of Utf1 causes embryonic lethality in mice with a hybrid
      genetic background. Male mice with a germline-specific deletion of Utf1 resulting
      from Prdm1-Cre mediated recombination are born with significantly fewer gonocytes
      and exhibit defective spermatogenesis and reduced sperm count as young adults.
      These defects are ameliorated in older animals. These results demonstrate that
      UTF1 is required for embryonic development and regulates male germ cell
      development.

PMID- 29222435
TI  - Long-term maintenance of peripheral blood derived human NK cells in a novel human
      IL-15- transgenic NOG mouse.
AB  - We generated a novel mouse strain expressing transgenic human interleukin-15 (IL
      15) using the severe immunodeficient NOD/Shi-scid-IL-2Rgamma null (NOG) mouse
      genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from
      the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when
      transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and
      the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft
      versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained
      the original expression patterns of various surface antigens, including NK
      receptors and killer cell immunoglobulin-like receptor (KIR) molecules. They also
      contained significant amounts of granzyme A and perforin. Inoculation of K562
      leukemia cells into hu-PB-NK-transplanted NOG-IL-15 Tg mice resulted in
      significant suppression of tumor growth compared with non-transplanted mice.
      Furthermore, NOG-IL-15 Tg mice allowed for engraftment of in vitro-expanded NK
      cells prepared for clinical cell therapy. These cells exerted antibody-dependent
      cell-mediated cytotoxicity (ADCC) on Her2-positive gastric cancer cells in the
      presence of therapeutic anti-Her2 antibody, and subsequently suppressed tumor
      growth. Our results collectively suggest that the NOG-IL-15 Tg mice are a useful
      model for studying human NK biology and evaluating human NK cell-mediated in vivo
      cytotoxicity.

PMID- 29222436
TI  - Weekly self-measurement of FEV1 and PEF and its impact on ACQ (asthma control
      questionnaire)-scores: 12-week observational study with 76 patients.
AB  - The "Asthma Control Questionnaire" (ACQ) is a very common questionnaire for
      assessing asthma control. This study compares different ACQ versions in a self
      monitoring program over a 12-week period combining them with patients' self
      measurements of peak expiratory flow (PEF) and forced expiratory volume in one
      second (FEV1). The objective was to test the feasibility of FEV1-self
      measurements and to compare ACQ versions regarding possible additional
      information given by lung function. In this prospective multicenter observational
      study 100 adult asthma patients, recruited at six family practices and two
      pulmologists' private practices in Germany, completed the ACQ weekly, performing
      self-measurements of PEF and FEV1. Seventy-six patients were included into final
      analysis with only 3% missing values. Scores for all ACQ versions improved
      significantly (all P-values < 0.05) with reductions of 32% for ACQ5, 31% for
      ACQ6, 22% for ACQ7-FEV1, and 21% for ACQ7-PEF with high Pearson's correlation
      coefficients of all scores (r between 0.96 and 0.99). ACQ7-FEV1 scores were
      significantly higher than others. Separated courses of lung function parameters
      showed nearly no change, but ACQ5 and ACQ6 as scores for symptoms and reliever
      medication improved constantly. ACQ5 and ACQ6 revealed higher percentages of
      patients classified as "controlled" than ACQ7-scores. In conclusion, with only a
      few missing data points, our results suggest feasibility of FEV1-self
      measurements. Courses of symptom-related and lung function-related ACQ items
      differ clearly. Our results support the GINA recommendations to consider symptoms
      and lung function separately. FEV1-self-measurements for research purposes may be
      included with the ACQ, but in clinical practice seem to measure a different
      domain to symptomatic asthma control.

PMID- 29222437
TI  - Digital-PCR for gene expression: impact from inherent tissue RNA degradation.
AB  - Subtle molecular differences indicate the heterogeneity present in a number of
      disease settings. Digital-PCR (dPCR) platforms achieve the necessary levels of
      sensitivity and accuracy over standard quantitative RT-PCR (qPCR) that promote
      their use for such situations, detecting low abundance transcript and subtle
      changes from gene expression. An underlying requisite is good quality RNA,
      principally dictated by appropriate tissue handling and RNA extraction. Here we
      consider the application of dPCR to measures of gene expression in pathological
      tissues with inherent necrosis, focusing on rheumatoid subcutaneous nodules.
      Variable RNA fragmentation is a feature of RNA from such tissues. Increased
      presence of transcript fragmentation is reflected in a proportionate decrease in
      Agilent DV200 metric and downstream, a reduction in endogenous control genes'
      expression, measured by RT-dPCR. We show that normalisation of target gene
      expression to that for endogenous control genes sufficiently corrects for the
      variable level of fragmented RNA. Recovery of target gene values was achieved in
      samples comprising as much as 50 percent fragmented RNA, indicating the
      suitability and appropriate limitation of such data treatment when applied to
      samples obtained from inherently necrotic tissues.

PMID- 29222438
TI  - New insights into the mechanism of nickel superoxide degradation from studies of
      model peptides.
AB  - A series of small, catalytically active metallopeptides, which were derived from
      the nickel superoxide dismutase (NiSOD) active site were employed to study the
      mechanism of superoxide degradation especially focusing on the role of the axial
      imidazole ligand. In the literature, there are contradicting propositions about
      the catalytic importance of the N-terminal histidine. Therefore, we studied the
      stability and activity of a set of eight NiSOD model peptides, which represent
      the major model systems discussed in the literature to date, yet differing in
      their length and their Ni-coordination. UV-Vis-coupled stopped-flow kinetic
      measurements and mass spectrometry analysis unveiled their high oxidation
      sensitivity in the presence of oxygen and superoxide resulting into a much faster
      Ni(II)-peptide degradation for the amine/amide Ni(II) coordination than for the
      catalytically inactive bis-amidate Ni(II) coordination. With respect to these
      results we determined the catalytic activities for all NiSOD mimics studied
      herein, which turned out to be in almost the same range of about 2 * 106 M-1 s-1.
      From these experiments, we concluded that the amine/amide Ni(II) coordination is
      clearly the key factor for catalytic activity. Finally, we were able to clarify
      the role of the N-terminal histidine and to resolve the contradictory literature
      propositions, reported in previous studies.

PMID- 29222440
TI  - Detection and measure of genuine tripartite entanglement with partial
      transposition and realignment of density matrices.
AB  - It is challenging task to detect and measure genuine multipartite entanglement.
      We investigate the problem by considering the average based positive partial
      transposition(PPT) criterion and the realignment criterion. Sufficient conditions
      for detecting genuine tripartite entanglement are presented. We also derive lower
      bounds for the genuine tripartite entanglement concurrence with respect to the
      conditions. While the PPT criterion and the realignment criterion are powerful
      for detecting bipartite entanglement and for providing lower bounds of bipartite
      concurrences, our results give an effective operational way to detect and measure
      the genuine tripartite entanglement.

PMID- 29222439
TI  - Alloy-assisted deposition of three-dimensional arrays of atomic gold catalyst for
      crystal growth studies.
AB  - Large-scale assembly of individual atoms over smooth surfaces is difficult to
      achieve. A configuration of an atom reservoir, in which individual atoms can be
      readily extracted, may successfully address this challenge. In this work, we
      demonstrate that a liquid gold-silicon alloy established in classical vapor
      liquid-solid growth can deposit ordered and three-dimensional rings of isolated
      gold atoms over silicon nanowire sidewalls. We perform ab initio molecular
      dynamics simulation and unveil a surprising single atomic gold-catalyzed chemical
      etching of silicon. Experimental verification of this catalytic process in
      silicon nanowires yields dopant-dependent, massive and ordered 3D grooves with
      spacing down to ~5 nm. Finally, we use these grooves as self-labeled and ex situ
      markers to resolve several complex silicon growths, including the formation of
      nodes, kinks, scale-like interfaces, and curved backbones.

PMID- 29222441
TI  - Robust RNA-based in situ mutation detection delineates colorectal cancer
      subclonal evolution.
AB  - Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance
      and disease recurrence, and is a read-out of tumor growth. Current genetic ITH
      analysis methods do not preserve spatial context and may not detect rare
      subclones. Here, we address these shortfalls by developing and validating
      BaseScope-a novel mutation-specific RNA in situ hybridization assay. We target
      common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival
      colorectal cancer samples to precisely map the spatial and morphological context
      of mutant subclones. Computational modeling suggests that subclones must arise
      sufficiently early, or carry a considerable fitness advantage, to form large or
      spatially disparate subclones. Examples of putative treatment-resistant cells
      isolated in small topographical areas are observed. The BaseScope assay
      represents a significant technical advance for in situ mutation detection that
      provides new insight into tumor evolution, and could have ramifications for
      selecting patients for treatment.

PMID- 29222442
TI  - Contrasting patterns of genome-level diversity across distinct co-occurring
      bacterial populations.
AB  - To understand the forces driving differentiation and diversification in wild
      bacterial populations, we must be able to delineate and track ecologically
      relevant units through space and time. Mapping metagenomic sequences to reference
      genomes derived from the same environment can reveal genetic heterogeneity within
      populations, and in some cases, be used to identify boundaries between
      genetically similar, but ecologically distinct, populations. Here we examine
      population-level heterogeneity within abundant and ubiquitous freshwater
      bacterial groups such as the acI Actinobacteria and LD12 Alphaproteobacteria (the
      freshwater sister clade to the marine SAR11) using 33 single-cell genomes and a 5
      year metagenomic time series. The single-cell genomes grouped into 15
      monophyletic clusters (termed "tribes") that share at least 97.9% 16S rRNA
      identity. Distinct populations were identified within most tribes based on the
      patterns of metagenomic read recruitments to single-cell genomes representing
      these tribes. Genetically distinct populations within tribes of the acI
      Actinobacterial lineage living in the same lake had different seasonal abundance
      patterns, suggesting these populations were also ecologically distinct. In
      contrast, sympatric LD12 populations were less genetically differentiated. This
      suggests that within one lake, some freshwater lineages harbor genetically
      discrete (but still closely related) and ecologically distinct populations, while
      other lineages are composed of less differentiated populations with overlapping
      niches. Our results point at an interplay of evolutionary and ecological forces
      acting on these communities that can be observed in real time.

PMID- 29222443
TI  - Metabolic versatility of small archaea Micrarchaeota and Parvarchaeota.
AB  - Small acidophilic archaea belonging to Micrarchaeota and Parvarchaeota phyla are
      known to physically interact with some Thermoplasmatales members in nature.
      However, due to a lack of cultivation and limited genomes on hand, their
      biodiversity, metabolisms, and physiologies remain largely unresolved. Here, we
      obtained 39 genomes from acid mine drainage (AMD) and hot spring environments
      around the world. 16S rRNA gene based analyses revealed that Parvarchaeota were
      only detected in AMD and hot spring habitats, while Micrarchaeota were also
      detected in others including soil, peat, hypersaline mat, and freshwater,
      suggesting a considerable higher diversity and broader than expected habitat
      distribution for this phylum. Despite their small genomes (0.64-1.08 Mb), these
      archaea may contribute to carbon and nitrogen cycling by degrading multiple
      saccharides and proteins, and produce ATP via aerobic respiration and
      fermentation. Additionally, we identified several syntenic genes with homology to
      those involved in iron oxidation in six Parvarchaeota genomes, suggesting their
      potential role in iron cycling. However, both phyla lack biosynthetic pathways
      for amino acids and nucleotides, suggesting that they likely scavenge these
      biomolecules from the environment and/or other community members. Moreover, low
      oxygen enrichments in laboratory confirmed our speculation that both phyla are
      microaerobic/anaerobic, based on several specific genes identified in them.
      Furthermore, phylogenetic analyses provide insights into the close evolutionary
      history of energy related functionalities between both phyla with
      Thermoplasmatales. These results expand our understanding of these elusive
      archaea by revealing their involvement in carbon, nitrogen, and iron cycling, and
      suggest their potential interactions with Thermoplasmatales on genomic scale.

PMID- 29222444
TI  - Diazotroph diversity and nitrogen fixation in the coral Stylophora pistillata
      from the Great Barrier Reef.
AB  - Diazotrophs, both Bacteria and Archaea, capable of fixing nitrogen (N2), are
      present in the tissues and mucous, of corals and can supplement the coral
      holobiont nitrogen budget with fixed nitrogen (N) in the form of ammonia (NH3).
      Stylophora pistillata from Heron Island on the Great Barrier Reef collected at 5
      and 15 m, and experimentally manipulated in the laboratory, showed that the rates
      of net photosynthesis, steady state quantum yields of photosystem II (PSII)
      fluorescence (?Fv/Fm') and calcification varied based on irradiance as expected.
      Rates of N2 fixation were, however, invariant across treatments while the amount
      of fixed N contributing to Symbiodinium spp. N demand is irradiance dependent.
      Additionally, both the Symbiodinium and diazotrophic communities are
      significantly different based on depth, and novel Cluster V nifH gene phylotypes,
      which are not known to fix nitrogen, were recovered. A functional analysis using
      PICRUSt also showed that shallow corals were enriched in genes involved in
      nitrogen metabolism, and N2 fixation specifically. Corals have evolved a number
      of strategies to derive nitrogen from organic (e.g., heterotrophic feeding) and
      inorganic sources (e.g., N2 fixation) to maintain critical pathways such as
      protein synthesis to succeed ecologically in nitrogen-limited habitats.

PMID- 29222445
TI  - Model-based genome-wide determination of RNA chain elongation rates in
      Escherichia coli.
AB  - Dynamics in the process of transcription are often simplified, yet they play an
      important role in transcript folding, translation into functional protein and DNA
      supercoiling. While the modulation of the speed of transcription of individual
      genes and its role in regulation and proper protein folding has been analyzed in
      depth, the functional relevance of differences in transcription speeds as well as
      the factors influencing it have not yet been determined on a genome-wide scale.
      Here we determined transcription speeds for the majority of E. coli genes based
      on experimental data. We find large differences in transcription speed between
      individual genes and a strong influence of both cellular location as well as the
      relative importance of genes for cellular function on transcription speeds.
      Investigating factors influencing transcription speeds we observe both codon
      composition as well as factors associated to DNA topology as most important
      factors influencing transcription speeds. Moreover, we show that differences in
      transcription speeds are sufficient to explain the timing of regulatory responses
      during environmental shifts and highlight the importance of the consideration of
      transcription speeds in the design of experiments measuring transcriptomic
      responses to perturbations.

PMID- 29222446
TI  - Demonstration of ultra-high recyclable energy densities in domain-engineered
      ferroelectric films.
AB  - Dielectric capacitors have the highest charge/discharge speed among all
      electrical energy devices, but lag behind in energy density. Here we report
      dielectric ultracapacitors based on ferroelectric films of Ba(Zr0.2,Ti0.8)O3
      which display high-energy densities (up to 166 J cm-3) and efficiencies (up to
      96%). Different from a typical ferroelectric whose electric polarization is
      easily saturated, these Ba(Zr0.2,Ti0.8)O3 films display a much delayed saturation
      of the electric polarization, which increases continuously from nearly zero at
      remnant in a multipolar state, to a large value under the maximum electric field,
      leading to drastically improved recyclable energy densities. This is achieved by
      the creation of an adaptive nano-domain structure in these perovskite films via
      phase engineering and strain tuning. The lead-free Ba(Zr0.2,Ti0.8)O3 films also
      show excellent dielectric and energy storage performance over a broad frequency
      and temperature range. These findings may enable broader applications of
      dielectric capacitors in energy storage, conditioning, and conversion.

PMID- 29222447
TI  - Structural abnormalities in islets from very young children with cystic fibrosis
      may contribute to cystic fibrosis-related diabetes.
AB  - Cystic fibrosis (CF)-related diabetes (CFRD) is thought to result from beta-cell
      injury due in part to pancreas exocrine damage and lipofibrosis. CFRD pancreata
      exhibit reduced islet density and altered cellular composition. To investigate a
      possible etiology, we tested the hypothesis that such changes are present in CF
      pancreata before the development of lipofibrosis. We evaluated pancreas and islet
      morphology in tissues from very young CF children (<4 years of age), and adult
      patients with CF and CFRD. The relative number of beta-cells in young CF tissues
      was reduced by 50% or more when compared to age-matched controls. Furthermore,
      young CF tissues displayed significantly smaller insulin-positive areas, lower
      proportion of beta-cells positive for the proliferation marker Ki67 or the ductal
      marker CK19 vs. control subjects, and islet inflammatory cell infiltrates,
      independently of the severity of the exocrine lesion and in the absence of
      amyloid deposits. CFRD pancreata exhibited greater islet injury with further
      reduction in islet density, decreased relative beta-cell number, and presence of
      amyloid deposits. Together, these results strongly suggest that an early
      deficiency in beta-cell number in infants with CF may contribute to the
      development of glucose intolerance in the CF pediatric population, and to CFRD,
      later in life.

PMID- 29222448
TI  - Effect of Qianghuo Erhuang Decoction on T Regulatory and T Helper 17 Cells in
      Treatment of Adjuvant-induced Arthritis in Rats.
AB  - QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid
      arthritis. The present study aimed to explore the effects of QED on Treg and Th17
      in adjuvant arthritis (AA) model. The study included 6 group rats: normal control
      group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose
      QED groups. The arthritis score was significantly decreased in the MTX and high
      dose QED groups compared with the AA group on days 24 and 28 (P < 0.01),
      respectively. The synovial tissue inflammation was attenuated by histological
      observation, and the proliferation of splenocytes was significantly inhibited in
      MTX and high-dose QED groups (P < 0.01). High-dose QED can up-regulated the
      percentage of Treg cells (P < 0.01) and down-regulated the percentage of Th17
      cells (P < 0.05). Notably, the serum levels of IL-6, IL-17 and TNF-alpha were
      significantly decreased, while TGF-beta levels were apparently elevated compared
      with AA group (P < 0.05, P < 0.01). Interestingly, moderate and low-dose QED had
      no such similar effects. In summary, high-dose QED had a therapeutic effect
      against adjuvant arthritis and regulated the related cytokine levels in serum.
      The underlying mechanism might be mediated via restoration of the imbalance in
      CD4+ T lymphocyte subsets, Treg/Th17.

PMID- 29222449
TI  - Detection of Prions in Blood of Cervids at the Asymptomatic Stage of Chronic
      Wasting Disease.
AB  - Chronic wasting disease (CWD) is a rapidly spreading prion disorder affecting
      captive and free-ranging cervids. The zoonotic potential of CWD is unknown, as
      well as the mechanism for its highly efficient transmission. A top priority to
      minimize further spreading of this disease and its potential impact on
      environmental prion contamination is the development of a non-invasive,
      sensitive, and specific test for ante-mortem detection of infected animals. Here,
      we optimized the protein misfolding cyclic amplification (PMCA) assay for highly
      efficient detection of CWD prions in blood samples. Studies were done using a
      blind panel of 98 field-collected samples of whole blood from codon 96
      glycine/glycine, captive white-tailed deer that were analyzed for prion infection
      post-mortem by immunohistochemistry (IHC). The results showed a sensitivity of
      100% in animals with very poor body condition that were IHC-positive in both
      brain and lymph nodes, 96% in asymptomatic deer IHC-positive in brain and lymph
      nodes and 53% in animals at early stages of infection that were IHC-positive only
      in lymph nodes. The overall mean diagnostic sensitivity was 79.3% with 100%
      specificity. These findings show that PMCA might be useful as a blood test for
      routine, live animal diagnosis of CWD.

PMID- 29222451
TI  - Alternate partial root-zone drip irrigation improves water- and nitrogen- use
      efficiencies of sweet-waxy maize with nitrogen fertigation.
AB  - Alternate partial root-zone drip irrigation (ADI) or fertigation has favorable
      effect on crop water- and nitrogen- use efficiencies (WUE and NUE). However, the
      advantage of combined application of ADI and nitrogen fertigation on crop WUE and
      NUE remains unclear. A pot experiment was conducted to investigate the impact of
      three irrigation methods (CDI conventional drip irrigation (both halves of pot
      irrigated), ADI (both halves of pot alternatively irrigated) and FDI fixed
      partial root-zone drip irrigation (fixed half of pot irrigated)) and five
      nitrogen treatments (F0 no N supplied, F1-F4 0.2, 0.18, 0.16 and 0.14 g N per kg
      soil via fertigation) on sweet-waxy maize. Compared with CDI, ADI reduced water
      consumption by 19.9%, but increased water use efficiency based on dry seed yield
      (WUEs) by 32.3%, and also enhanced nitrogen apparent recovery fraction (Nrf) and
      nitrogen agronomic efficiency (NAE). F1-F4 augmented dry mass accumulation, dry
      seed yield and total nitrogen uptake if compared to F0. Moreover, F2-ADI had
      higher shoot and total dry masses, WUEs, total nitrogen uptake, Nrf and NAE. Thus
      ADI increased nitrogen uptake, WUE and NUE of sweet-waxy maize with nitrogen
      fertigation of 0.18 g N per kg soil in this study.

PMID- 29222450
TI  - Elevation of autophagy markers in Sjogren syndrome dry eye.
AB  - Autophagy is known to be implicated in the pathogenesis of Sjogren syndrome (SS),
      but evidences are limited. We aimed to examine the levels of autophagy markers in
      tear film and conjunctival epithelial cells from SS dry eye patients, and analyze
      their correlations with clinical features. Patients with SS dry eye exhibited
      lower Schirmer values, lower tear breakup time, and higher ocular staining
      scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry
      eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye
      compared with non-SS dry eye. The immunostaining of conjunctival epithelium
      showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining
      patterns were also observed in the lacrimal gland of SS animal models. ATG5
      levels in tears and the conjunctival epithelium strongly correlated with ocular
      staining scores, and one month of topical corticosteroid treatment reduced both
      ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of
      patients with SS dry eye. Our results suggest that autophagy is enhanced or
      dysregulated in SS and autophagy markers may be serve as both diagnostic and
      therapeutic biomarkers in SS dry eye.

PMID- 29222452
TI  - Enhanced electronic-transport modulation in single-crystalline VO2 nanowire-based
      solid-state field-effect transistors.
AB  - Field-effect transistors using correlated electron materials with an electronic
      phase transition pave a new avenue to realize steep slope switching, to overcome
      device size limitations and to investigate fundamental science. Here, we present
      a new finding in gate-bias-induced electronic transport switching in a correlated
      electron material, i.e., a VO2 nanowire channel through a hybrid gate, which
      showed an enhancement in the resistive modulation efficiency accompanied by
      expansion of metallic nano-domains in an insulating matrix by applying gate
      biases near the metal-insulator transition temperature. Our results offer an
      understanding of the innate ability of coexistence state of metallic and
      insulating domains in correlated materials through carrier tuning and serve as a
      valuable reference for further research into the development of correlated
      materials and their devices.

PMID- 29222453
TI  - Transcriptome analysis of Brachypodium during fungal pathogen infection reveals
      both shared and distinct defense responses with wheat.
AB  - Fusarium crown rot (FCR) of wheat and barley, predominantly caused by the fungal
      pathogen Fusarium pseudograminearum, is a disease of economic significance. The
      quantitative nature of FCR resistance within cultivated wheat germplasm has
      significantly limited breeding efforts to enhanced FCR resistance in wheat. In
      this study, we characterized the molecular responses of Brachypodium distachyon
      (Brachypodium hereafter) to F. pseudograminearum infection using RNA-seq to
      determine whether Brachypodium can be exploited as a model system towards better
      understanding of F. pseudograminearum-wheat interaction. The transcriptional
      response to infection in Brachypodium was strikingly similar to that previously
      reported in wheat, both in shared expression patterns of wheat homologs of
      Brachypodium genes and functional overlap revealed through comparative gene
      ontology analysis in both species. Metabolites produced by various biosynthetic
      pathways induced in both wheat and Brachypodium were quantified, revealing a high
      degree of overlap between these two species in metabolic response to infection
      but also showed Brachypodium does not produce certain defence-related metabolites
      found in wheat. Functional analyses of candidate genes identified in this study
      will improve our understanding of resistance mechanisms and may lead to the
      development of new strategies to protect cereal crops from pathogen infection.

PMID- 29222454
TI  - Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis.
AB  - The proteoglycan versican is implicated in growth and metastases of several
      cancers. Here we investigated a potential contribution of stromal versican to
      tumor growth and angiogenesis. We initially determined versican expression by
      several cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal
      expression in contrast to Lewis lung carcinoma (LLC). Notably, tumors arising
      from these cell lines had higher versican levels than the cell lines themselves
      suggesting a contribution from the host-derived tumor stroma. In LLC-derived
      tumors, both the tumor and stroma expressed versican at high levels. Thus, tumor
      stroma can make a significant contribution to tumor versican content. Versican
      localized preferentially to the vicinity of tumor vasculature and macrophages in
      the tumor. However, an ADAMTS protease-generated versican fragment uniquely
      localized to vascular endothelium. To specifically determine the impact of
      host/stroma-derived versican we therefore compared growth of tumors from B16F10
      cells, which produced littleversican, in Vcan hdf/+ mice and wild-type
      littermates. Tumors in Vcan hdf/+ mice had reduced growth with a lower capillary
      density and accumulation of capillaries at the tumor periphery. These findings
      illustrate the variability of tumor cell line expression of versican, and
      demonstrate that versican is consistently contributed by the stromal tissue,
      where it contributes to tumor angiogenesis.

PMID- 29222455
TI  - Binding Modes of Teixobactin to Lipid II: Molecular Dynamics Study.
AB  - Teixobactin (TXB) is a newly discovered antibiotic targeting the bacterial cell
      wall precursor Lipid II (LII). In the present work, four binding modes of TXB on
      LII were identified by a contact-map based clustering method. The highly flexible
      binary complex ensemble was generated by parallel tempering metadynamics
      simulation in a well-tempered ensemble (PTMetaD-WTE). In agreement with
      experimental findings, the pyrophosphate group and the attached first sugar
      subunit of LII are found to be the minimal motif for stable TXB binding. Three of
      the four binding modes involve the ring structure of TXB and have relatively
      higher binding affinities, indicating the importance of the ring motif of TXB in
      LII recognition. TXB-LII complexes with a ratio of 2:1 are also predicted with
      configurations such that the ring motif of two TXB molecules bound to the
      pyrophosphate-MurNAc moiety and the glutamic acid residue of one LII,
      respectively. Our findings disclose that the ring motif of TXB is critical to LII
      binding and novel antibiotics can be designed based on its mimetics.

PMID- 29222457
TI  - A control analysis perspective on Katz centrality.
AB  - Methods for efficiently controlling dynamics propagated on networks are usually
      based on identifying the most influential nodes. Knowledge of these nodes can be
      used for the targeted control of dynamics such as epidemics, or for modifying
      biochemical pathways relating to diseases. Similarly they are valuable for
      identifying points of failure to increase network resilience in, for example,
      social support networks and logistics networks. Many measures, often termed
      'centrality', have been constructed to achieve these aims. Here we consider Katz
      centrality and provide a new interpretation as a steady-state solution to
      continuous-time dynamics. This enables us to implement a sensitivity analysis
      which is similar to metabolic control analysis used in the analysis of
      biochemical pathways. The results yield a centrality which quantifies, for each
      node, the net impact of its absence from the network. It also has the desirable
      property of requiring a node with a high centrality to play a central role in
      propagating the dynamics of the system by having the capacity to both receive
      flux from others and then to pass it on. This new perspective on Katz centrality
      is important for a more comprehensive analysis of directed networks.

PMID- 29222456
TI  - BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1
      adipocytes via PPARgamma and GLUT4 upregulation.
AB  - Insulin-resistance is the main cause of type 2 diabetes. Here we describe the
      identification and characterization of BMP2 and BMP6 as new insulin-sensitizing
      growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced
      insulin-mediated glucose uptake in both insulin-sensitive and -insensitive
      adipocytes. We exclude a direct effect of BMP2 or BMP6 on translocation of GLUT4
      to the plasma membrane and demonstrate that these BMPs increase GLUT4 protein
      levels equipotent to Rosiglitazone. BMPs induce expression of PPARgamma as the
      crucial mediator for the insulin-sensitizing effect. A comprehensive RNA-Seq
      analysis in mature adipocytes revealed regulation of both BMP/Smad and PPARgamma
      target genes. The effects of BMP2 and BMP6 are not completely redundant and
      include regulation of genes involved in glucose and fatty acid metabolism and
      adipokine expression. Collectively, these findings suggest the BMP2 and BMP6
      pathway(s) as promising new drug targets to treat insulin resistance.

PMID- 29222458
TI  - Serendipity and strategy in rapid innovation.
AB  - Innovation is to organizations what evolution is to organisms: it is how
      organizations adapt to environmental change and improve. Yet despite advances in
      our understanding of evolution, what drives innovation remains elusive. On the
      one hand, organizations invest heavily in systematic strategies to accelerate
      innovation. On the other, historical analysis and individual experience suggest
      that serendipity plays a significant role. To unify these perspectives, we
      analysed the mathematics of innovation as a search for designs across a universe
      of component building blocks. We tested our insights using data from language,
      gastronomy and technology. By measuring the number of makeable designs as we
      acquire components, we observed that the relative usefulness of different
      components can cross over time. When these crossovers are unanticipated, they
      appear to be the result of serendipity. But when we can predict crossovers in
      advance, they offer opportunities to strategically increase the growth of the
      product space.

PMID- 29222459
TI  - Uncovering heterogeneous interactions in online commercial networks.
AB  - With the rapid development of Internet, the research on online commercial
      networks has become crucial for filtering out irrelevant information for users
      and predicting their future interest. The common methods for understanding such
      typical user-item networks are mainly projecting them to unipartite ones with
      only positive ratings, which may result in losing a large amount of information.
      In this paper, we propose a novel approach to construct a signed unipartite
      network with heterogeneous interactions (i.e. positive or negative) between users
      from the original bipartite network. Based on the signed similarity, we carry out
      the percolation analysis on this signed unipartite network, which reveals a phase
      transition phenomenon. The statistical features of the giant component consisting
      of the positive and negative interactions are investigated respectively. Finally,
      the roles of the negative links and weak ties are revealed by adding them back to
      the giant component. This work not only deepens our understanding of the online
      commercial networks, but also has potential applications in the design of
      recommendation algorithms.

PMID- 29222460
TI  - Laminar flow drag reduction on soft porous media.
AB  - While researches have focused on drag reduction of various coated surfaces such
      as superhydrophobic structures and polymer brushes, the insights tso understand
      the fundamental physics of the laminar skin friction coefficient and the related
      drag reduction due to the formation of finite velocity at porous surfaces is
      still relatively unknown. Herein, we quantitatively investigated the flow over a
      porous medium by developing a framework to model flow of a Newtonian fluid in a
      channel where the lower surface was replaced by various porous media. We showed
      that the flow drag reduction induced by the presence of the porous media depends
      on the values of the permeability parameter alpha = L/(MK)1/2 and the height
      ratio delta = H/L, where L is the half thickness of the free flow region, H is
      the thickness and K is the permeability of the fiber layer, and M is the ratio of
      the fluid effective dynamic viscosity MUe in porous media to its dynamic
      viscosity MU. We also examined the velocity and shear stress profiles for flow
      over the permeable layer for the limiting cases of alpha -> 0 and alpha ->
      infinity. The model predictions were compared with the experimental data for
      specific porous media and good agreement was found.

PMID- 29222461
TI  - Tree co-occurrence and transcriptomic response to drought.
AB  - The distribution and co-occurrence of species are partly the outcome of their
      interactions with environmental drivers. Drought is a key driver related to the
      distribution of plant species. Drought events continue to increase in frequency
      and severity and identifying those aspects of plant function that are related to
      drought is critical. Here, we perform a community-level analysis of gene
      expression in relation to experimental drought and relate the similarity in gene
      set enrichment across species to their natural co-occurrence. Species with
      similar gene set enrichment in response to experimental drought tend to non
      randomly co-occur in a natural stand. We demonstrate that similarity in the
      transcriptomic response of species to drought is a significantly better indicator
      of natural co-occurrence than measures of functional trait similarity and
      phylogenetic relatedness and that transcriptomics has the capacity to greatly
      enhance ecological investigations of species distributions and community
      structure.

PMID- 29222462
TI  - A translational model to determine rodent's age from human foetal age.
AB  - To understand the prenatal origin of developmental and psychiatric disorders,
      studies in laboratory animals are imperative. However, the developmental pace
      differs between humans and animals; hence, corresponding human ages must be
      estimated to infer the most vulnerable developmental timings in humans. Because
      rats and mice are extensively used as models in developmental research, a
      correspondence between human foetal ages and rodents' ages must be precisely
      determined; thus, developing a translational model is of utmost importance.
      Optimizing a translational model involves classifying the brain regions according
      to developmental paces, but previous studies have conducted this classification
      arbitrarily. Here we used a clustering method and showed that the brain regions
      can be classified into two groups. To quantify the developmental pace, we
      gathered data for a range of development events in humans and rodents and created
      a linear mixed model that translates human developmental timings into the
      corresponding rat timings. We conducted an automatic classification of brain
      regions using an EM algorithm and obtained a model to translate human foetal age
      to rat age. Our model could predict rat developmental timings within 2.5 days of
      root mean squared error. This result provides useful information for designing
      animal studies and clinical tests.

PMID- 29222463
TI  - The genome sequence of Bipolaris cookei reveals mechanisms of pathogenesis
      underlying target leaf spot of sorghum.
AB  - Bipolaris cookei (=Bipolaris sorghicola) causes target leaf spot, one of the most
      prevalent foliar diseases of sorghum. Little is known about the molecular basis
      of pathogenesis in B. cookei, in large part due to a paucity of resources for
      molecular genetics, such as a reference genome. Here, a draft genome sequence of
      B. cookei was obtained and analyzed. A hybrid assembly strategy utilizing
      Illumina and Pacific Biosciences sequencing technologies produced a draft nuclear
      genome of 36.1 Mb, organized into 321 scaffolds with L50 of 31 and N50 of 378 kb,
      from which 11,189 genes were predicted. Additionally, a finished mitochondrial
      genome sequence of 135,790 bp was obtained, which contained 75 predicted genes.
      Comparative genomics revealed that B. cookei possessed substantially fewer
      carbohydrate-active enzymes and secreted proteins than closely related Bipolaris
      species. Novel genes involved in secondary metabolism, including genes implicated
      in ophiobolin biosynthesis, were identified. Among 37 B. cookei genes induced
      during sorghum infection, one encodes a putative effector with a limited
      taxonomic distribution among plant pathogenic fungi. The draft genome sequence of
      B. cookei provided novel insights into target leaf spot of sorghum and is an
      important resource for future investigation.

PMID- 29222464
TI  - The Irish DNA Atlas: Revealing Fine-Scale Population Structure and History within
      Ireland.
AB  - The extent of population structure within Ireland is largely unknown, as is the
      impact of historical migrations. Here we illustrate fine-scale genetic structure
      across Ireland that follows geographic boundaries and present evidence of
      admixture events into Ireland. Utilising the 'Irish DNA Atlas', a cohort (n =
      194) of Irish individuals with four generations of ancestry linked to specific
      regions in Ireland, in combination with 2,039 individuals from the Peoples of the
      British Isles dataset, we show that the Irish population can be divided in 10
      distinct geographically stratified genetic clusters; seven of 'Gaelic' Irish
      ancestry, and three of shared Irish-British ancestry. In addition we observe a
      major genetic barrier to the north of Ireland in Ulster. Using a reference of
      6,760 European individuals and two ancient Irish genomes, we demonstrate high
      levels of North-West French-like and West Norwegian-like ancestry within Ireland.
      We show that that our 'Gaelic' Irish clusters present homogenous levels of
      ancient Irish ancestries. We additionally detect admixture events that provide
      evidence of Norse-Viking gene flow into Ireland, and reflect the Ulster
      Plantations. Our work informs both on Irish history, as well as the study of
      Mendelian and complex disease genetics involving populations of Irish ancestry.

PMID- 29222465
TI  - The dynamic dimer structure of the chaperone Trigger Factor.
AB  - The chaperone Trigger Factor (TF) from Escherichia coli forms a dimer at cellular
      concentrations. While the monomer structure of TF is well known, the spatial
      arrangement of this dimeric chaperone storage form has remained unclear. Here, we
      determine its structure by a combination of high-resolution NMR spectroscopy and
      biophysical methods. TF forms a symmetric head-to-tail dimer, where the ribosome
      binding domain is in contact with the substrate binding domain, while the
      peptidyl-prolyl isomerase domain contributes only slightly to the dimer affinity.
      The dimer structure is highly dynamic, with the two ribosome binding domains
      populating a conformational ensemble in the center. These dynamics result from
      intermolecular in trans interactions of the TF client-binding site with the
      ribosome binding domain, which is conformationally frustrated in the absence of
      the ribosome. The avidity in the dimer structure explains how the dimeric state
      of TF can be monomerized also by weakly interacting clients.

PMID- 29222467
TI  - Elemental preference and atomic scale site recognition in a Co-Al-W-base
      superalloy.
AB  - Using state-of-the-art atomic scale super energy dispersive X-ray spectroscopy
      and high angle annular dark field imaging this study reveals the elemental
      partitioning preference between the gamma' and gamma phases in a Co-Al-W-Ti-Ta
      superalloy and the site preference of its alloying elements in the ordered L12
      gamma' phase. A semi-quantitative analysis of atomic column compositions in the
      ordered L12 gamma' structure is provided. Co atoms were found to occupy the {1/2,
      1/2, 0} face-center positions whereas Al, W, Ti and Ta atoms prefer to occupy the
      {0, 0, 0} cube corner positions in the L12 gamma phase. These findings agree well
      with predictions from first principles simulations in the literature.

PMID- 29222466
TI  - Deciphering transcriptional regulation in human embryonic stem cells specified
      towards a trophoblast fate.
AB  - Differentiated human embryonic stem cells (hESC) continue to provide a model for
      studying early trophoblast cells (TB), but many questions have been raised
      regarding their true identity. Therefore, we carried out a global and unbiased
      analysis on previously published transcriptomic profiles for hESC differentiated
      to TB by means of bone morphogenetic protein-4 and inhibitors of activin A and
      fibroblast growth factor-2 signaling (BAP treatment). Our results confirm that
      BAP treated hESC (ESCd) lack a mesoderm signature and are a subtype of placental
      cells unlike those present at term. ESCd display a high level of expression of
      genes implicated in migration and invasion compared to commonly used,
      immortalized TB cell lines and primary cells from term placenta. Co-expression
      network analysis also identified gene modules involved in cell migration and
      adhesion, processes that are likely critical during the beginning stages of
      placentation. Finally, protein-protein interaction analysis predicted several
      additional genes that may play important roles in early stages of placental
      development. Together, our analyses provide novel insights into the
      transcriptional programs that are active in ESCd.

PMID- 29222468
TI  - Dissecting the Genetic Basis of Local Adaptation in Soybean.
AB  - Soybean (Glycine max) is the most widely grown oilseed in the world and is an
      important source of protein for both humans and livestock. Soybean is widely
      adapted to both temperate and tropical regions, but a changing climate demands a
      better understanding of adaptation to specific environmental conditions. Here, we
      explore genetic variation in a collection of 3,012 georeferenced, locally adapted
      landraces from a broad geographical range to help elucidate the genetic basis of
      local adaptation. We used geographic origin, environmental data and dense genome
      wide SNP data to perform an environmental association analysis and discover loci
      displaying steep gradients in allele frequency across geographical distance and
      between landrace and modern cultivars. Our combined application of methods in
      environmental association mapping and detection of selection targets provide a
      better understanding of how geography and selection may have shaped genetic
      variation among soybean landraces. Moreover, we identified several important
      candidate genes related to drought and heat stress, and revealed important
      genomic regions possibly involved in the geographic divergence of soybean.

PMID- 29222470
TI  - Remote control of resistive switching in TiO2 based resistive random access
      memory device.
AB  - We report on the magnetic field control of a bipolar resistive switching in
      Ag/TiO2/FTO based resistive random access memory device through I-V
      characteristics. Essentially, in the presence of magnetic field and in the low
      resistance state, an abrupt change in the resistance of the device demands higher
      voltage, hinting that residual Lorentz force plays a significant role in
      controlling the resistance state. Endurance characteristics of the device infer
      that there is no degradation of the device even after repeated cycling, which
      ensures that the switching of resistance between 'off' and 'on' states is
      reproducible, reversible and controllable. Magnetic field control of 'on' and
      'off' states in endurance characteristics suggest that this device can be
      controlled in a remote way for multi-bit data storage.

PMID- 29222469
TI  - Hippocampal oxytocin receptors are necessary for discrimination of social
      stimuli.
AB  - Oxytocin receptor (Oxtr) signaling in neural circuits mediating discrimination of
      social stimuli and affiliation or avoidance behavior is thought to guide social
      recognition. Remarkably, the physiological functions of Oxtrs in the hippocampus
      are not known. Here we demonstrate using genetic and pharmacological approaches
      that Oxtrs in the anterior dentate gyrus (aDG) and anterior CA2/CA3 (aCA2/CA3) of
      mice are necessary for discrimination of social, but not non-social, stimuli.
      Further, Oxtrs in aCA2/CA3 neurons recruit a population-based coding mechanism to
      mediate social stimuli discrimination. Optogenetic terminal-specific attenuation
      revealed a critical role for aCA2/CA3 outputs to posterior CA1 for discrimination
      of social stimuli. In contrast, aCA2/CA3 projections to aCA1 mediate
      discrimination of non-social stimuli. These studies identify a role for an aDG
      CA2/CA3 axis of Oxtr expressing cells in discrimination of social stimuli and
      delineate a pathway relaying social memory computations in the anterior
      hippocampus to the posterior hippocampus to guide social recognition.

PMID- 29222472
TI  - Long Noncoding RNA HOTAIR Modulates MiR-206-mediated Bcl-w Signaling to
      Facilitate Cell Proliferation in Breast Cancer.
AB  - LncRNA HOX transcript antisense RNA (HOTAIR) is involved in lots of cancers. The
      pro-survival protein Bcl-w is frequently found in cancer development. However,
      the effect of HOTAIR on Bcl-w in breast cancer is not well documented. In this
      study, we first evaluated the correlation between HOTAIR level and Bcl-w
      expression in clinical breast cancer tissues. We observed that the expression
      levels of Bcl-w were much higher in the breast cancer samples than that in their
      paired noncancerous tissues. Moreover, the levels of HOTAIR were positively
      associated with those of Bcl-w in clinical breast cancer samples. As expected, we
      observed that HOTAIR was able to up-regulate the expression of Bcl-w in breast
      cancer cells. Mechanistically, we found that miR-206 was capable of inhibiting
      the expression of Bcl-w by directly binding to the 3'UTR of Bcl-w mRNA.
      Interestingly, HOTAIR could increase the expression of Bcl-w through sequestering
      miR-206 at post-transcriptional level. Functionally, our data showed that HOTAIR
      induced Bcl-w by miR-206 facilitated the proliferation of breast cancer cells.
      Thus, we conclude that HOTAIR up-regulates Bcl-w to enhance cell proliferation
      through sequestering miR-206 in breast cancer. Our finding provides new insights
      into the mechanism of breast cancer mediated by HOTAIR.

PMID- 29222471
TI  - Spatial competition constrains resistance to targeted cancer therapy.
AB  - Adaptive therapy (AT) aims to control tumour burden by maintaining therapy
      sensitive cells to exploit their competition with resistant cells. This relies on
      the assumption that resistant cells have impaired cellular fitness. Here, using a
      model of resistance to a pharmacological cyclin-dependent kinase inhibitor
      (CDKi), we show that this assumption is valid when competition between cells is
      spatially structured. We generate CDKi-resistant cancer cells and find that they
      have reduced proliferative fitness and stably rewired cell cycle control
      pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden
      and resistance in tumour spheroids, but not in monolayer culture. Mathematical
      modelling indicates that tumour spatial structure amplifies the fitness penalty
      of resistant cells, and identifies their relative fitness as a critical
      determinant of the clinical benefit of AT. Our results justify further
      investigation of AT with kinase inhibitors.

PMID- 29222473
TI  - Hypoxia-inducible factor 1alpha is Essential for Macrophage-mediated Erythroblast
      Proliferation in Acute Friend Retrovirus Infection.
AB  - Macrophages are the frontline of defence against foreign microorganisms,
      including bacteria, parasites, and viruses. During acute viral infection,
      macrophages must invade the inflamed tissue toward low oxygen concentrations,
      where genetic cellular responses depend on hypoxia-inducible factors (HIF). In
      the study reported here we investigated the role of HIF-1alpha in macrophage
      function during acute retroviral infection. Wild-type and myeloid cell-specific
      HIF-1alpha knockout mice were infected with Friend retrovirus (FV), and immune
      response was analysed 7 and 10 days after infection. FV infection led to
      increased spleen weight in wild-type and knockout mice, whereas a profound
      proliferation of erythroblasts was seen only in wild-type mice. The number of
      spleen-infiltrating macrophages was also significantly lower in knockout animals.
      Macrophage invasion after FV infection in wild-type mice led to elevated amounts
      of activated macrophage-stimulating 1 protein that resulted in massive
      proliferation of erythrocyte precursor cells. This proliferation was absent from
      knockout mice because of impaired invasion capabilities of HIF-1alpha-deficient
      macrophages. Our study elucidated a novel mechanism of FV-induced erythrocyte
      precursor cell proliferation.

PMID- 29222474
TI  - A nontrivial crossover in topological Hall effect regimes.
AB  - We propose a new theory of the topological Hall effect (THE) in systems with non
      collinear magnetization textures such as magnetic skyrmions. We solve the problem
      of electron scattering on a magnetic skyrmion exactly, for an arbitrary strength
      of exchange interaction and the skyrmion size. We report the existence of
      different regimes of THE and resolve the apparent contradiction between the
      adiabatic Berry phase theoretical approach and the perturbation theory for THE.
      We traced how the topological charge Hall effect transforms into the spin Hall
      effect upon varying the exchange interaction strength or the skyrmion size. This
      transformation has a nontrivial character: it is accompanied by an oscillating
      behavior of both charge and spin Hall currents. This hallmark of THE allows one
      to identify the chirality driven contribution to Hall response in the
      experiments.

PMID- 29222475
TI  - Suitability of various chromatographic and spectroscopic techniques for analysis
      and kinetic degradation study of trelagliptin.
AB  - Multifaceted comparative analytical methods for trelagliptin (TRL) were
      investigated, applied to ZAFATEK tablets and HPLC-UV was selected for a
      degradation kinetic study. UPLC-MS/MS (Method I), UPLC-UV (Method II), HPLC-UV
      (Method III), UHPLC-UV (Method IV) and direct UV (Method V) methods were
      developed. Methods (I-V) showed satisfactory results using TRL concentration
      ranges of 50-800 ng/mL, 2.5-80 MUg/mL, 5-100 MUg/mL, 5-100 MUg/mL and 5-50
      MUg/mL, respectively. Multiple Reaction Monitoring (MRM) of the transition pairs
      of m/z 358.176 to 134.127 for TRL and m/z 340.18 to 116.08 for alogliptin (IS)
      were employed utilizing positive mode Electrospray Ionization (ESI). The
      degradation kinetic study (Method VI) was carried out using 1 N HCl based on
      three different temperatures (70  degrees C, 80  degrees C and 90  degrees C).
      Through the optimized method-3, a good chromatographic separation of TRL from its
      major degradation product was achieved. Arrhenius plot was used in the kinetic
      study and the apparent 1st order degradation rate constant (K), t1/2, t90, and
      the activation energies were calculated for each temperature and at 25  degrees
      C. The optimized UPLC-MS/MS method is suitable for further TRL assay either in
      biological fluids or in the presence of impurities.

PMID- 29222476
TI  - Morphophysiological mechanism of rice yield increase in response to optimized
      nitrogen management.
AB  - The yield-increasing mechanism of an optimized nitrogen fertilizer application
      (OFA) in rice was reported in this work through a three-year test. Results showed
      that the number of branches and spikelets increased, panicle length, the diameter
      and vascular bundle number of panicle-neck internode improved with OFA. Under the
      condition of OFA, high effective leaf areas, especially for the flag and the
      second upper leaf areas, increased, the net photosynthetic rate of the upper
      three leaves promoted, so the photosynthetic productivity went up by a large
      margin; moreover, the content of soluble protein and chlorophyll of leaf also
      increased, and the content of soluble sugar and malondialdehyde (MDA) decreased,
      as a result in slowing down the senescence speed in leaves, and increasing the
      photosynthetic time. Gene expression level, including MOC1, LAX1, SP1, GS1;1,
      were up-regulated obviously in different panicle initiation stage under OFA
      condition, which conduced to the increase in the secondary branches and
      spikelets. So we concluded that the changes in organ formation and panicle
      structure, together with the responses in physiological and molecular made the
      photosynthetic area, rate and time all increased with OFA, which provided the
      matter basis for the big panicle development, consequently, got a higher yield.

PMID- 29222478
TI  - Viscosity jump in the lower mantle inferred from melting curves of
      ferropericlase.
AB  - Convection provides the mechanism behind plate tectonics, which allows oceanic
      lithosphere to be subducted into the mantle as "slabs" and new rock to be
      generated by volcanism. Stagnation of subducting slabs and deflection of rising
      plumes in Earth's shallow lower mantle have been suggested to result from a
      viscosity increase at those depths. However, the mechanism for this increase
      remains elusive. Here, we examine the melting behavior in the MgO-FeO binary
      system at high pressures using the laser-heated diamond-anvil cell and show that
      the liquidus and solidus of (Mg x Fe1-x )O ferropericlase (x = ~0.52-0.98),
      exhibit a local maximum at ~40 GPa, likely caused by the spin transition of iron.
      We calculate the relative viscosity profiles of ferropericlase using homologous
      temperature scaling and find that viscosity increases 10-100 times from ~750 km
      to ~1000-1250 km, with a smaller decrease at deeper depths, pointing to a single
      mechanism for slab stagnation and plume deflection.

PMID- 29222477
TI  - A Novel EEG Based Spectral Analysis of Persistent Brain Function Alteration in
      Athletes with Concussion History.
AB  - The neurocognitive sequelae of a sport-related concussion and its management are
      poorly defined. Detecting deficits are vital in making a decision about the
      treatment plan as it can persist one year or more following a brain injury. The
      reliability of traditional cognitive assessment tools is debatable, and thus
      attention has turned to assessments based on electroencephalogram (EEG) to
      evaluate subtle post-concussive alterations. In this study, we calculated
      neurocognitive deficits combining EEG analysis with three standard post
      concussive assessment tools. Data were collected for all testing modalities from
      21 adolescent athletes (seven concussive and fourteen healthy) in three different
      trials. For EEG assessment, along with linear frequency-based features, we
      introduced a set of time-frequency (Hjorth Parameters) and nonlinear features
      (approximate entropy and Hurst exponent) for the first time to explore post
      concussive deficits. Besides traditional frequency-band analysis, we also
      presented a new individual frequency-based approach for EEG assessment. While EEG
      analysis exhibited significant discrepancies between the groups, none of the
      cognitive assessment resulted in significant deficits. Therefore, the evidence
      from the study highlights that our proposed EEG analysis and markers are more
      efficient at deciphering post-concussion residual neurocognitive deficits and
      thus has a potential clinical utility of proper concussion assessment and
      management.

PMID- 29222479
TI  - GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced
      liver injury.
AB  - Growth differentiation factor 15 (GDF15) has recently been shown to have an
      important role in the regulation of mitochondrial function and in the
      pathogenesis of complex human diseases. Nevertheless, the role of GDF15 in
      alcohol-induced or fibrotic liver diseases has yet to be determined. In this
      study, we demonstrate that alcohol- or carbon tetrachloride (CCl4)-mediated
      hepatic GDF15 production ameliorates liver inflammation and fibrosis. Alcohol
      directly enhanced GDF15 expression in primary hepatocytes, which led to increased
      oxygen consumption. Moreover, GDF15 reduced the expression of pro-inflammatory
      cytokines in liver-resident macrophages, leading to an improvement in
      inflammation and fibrosis in the liver. GDF15 knockout (KO) mice had more TNF
      alpha-producing T cells and more activated CD4+ and CD8+ T cells in the liver
      than wild-type mice. Liver-infiltrating monocytes and neutrophils were also
      increased in the GDF15 KO mice during liver fibrogenesis. These changes in
      hepatic immune cells were associated with increased tissue inflammation and
      fibrosis. Finally, recombinant GDF15 decreased the expression of pro-inflammatory
      cytokines and fibrotic mediators and prevented the activation of T cells in the
      livers of mice with CCl4-induced liver fibrosis. These results suggest that GDF15
      could be a potential therapeutic target for the treatment of alcohol-induced and
      fibrotic liver diseases.

PMID- 29222480
TI  - A tyrosinase, mTyr-CNK, that is functionally available as a monophenol
      monooxygenase.
AB  - Tyrosinase efficiently catalyzes the ortho-hydroxylation of monophenols and the
      oxidation of diphenols without any additional cofactors. Although it is of
      significant interest for the biosynthesis of catechol derivatives, the rapid
      catechol oxidase activity and inactivation of tyrosinase have hampered its
      practical utilization as a monophenol monooxygenase. Here, we prepared a
      functional tyrosinase that exhibited a distinguished monophenolase/diphenolase
      activity ratio (V max mono/ V max di = 3.83) and enhanced catalytic efficiency
      against L-tyrosine (k cat  = 3.33 +/- 0.18 s-1, K m  = 2.12 +/- 0.14 mM at 20 
      degrees C and pH 6.0). This enzyme was still highly active in ice water (>80%),
      and its activity was well conserved below 30  degrees C. In vitro DOPA
      modification, with a remarkably high yield as a monophenol monooxygenase, was
      achieved by the enzyme taking advantage of these biocatalytic properties. These
      results demonstrate the strong potential for this enzyme's use as a monophenol
      monooxygenase in biomedical and industrial applications.

PMID- 29222481
TI  - Hypoxia-inducible factor prolyl-4-hydroxylase-1 is a convergent point in the
      reciprocal negative regulation of NF-kappaB and p53 signaling pathways.
AB  - Hypoxia-inducible factor 1alpha (HIF1alpha) induces the expression of several
      hundred genes in hypoxia aiming at restoration of oxygen homeostasis. HIF prolyl
      4-hydroxylases (HIF-P4Hs) regulate the stability of HIF1alpha in an oxygen
      dependent manner. Hypoxia is a common feature in inflammation and cancer and the
      HIF pathway is closely linked with the inflammatory NF-kappaB and tumor
      suppressor p53 pathways. Here we show that genetic inactivation or chemical
      inhibition of HIF-P4H-1 leads to downregulation of proinflammatory genes, while
      proapoptotic genes are upregulated. HIF-P4H-1 inactivation reduces the
      inflammatory response under LPS stimulus in vitro and in an acute skin
      inflammation model in vivo. Furthermore, HIF-P4H-1 inactivation increases p53
      activity and stability and hydroxylation of proline 142 in p53 has an important
      role in this regulation. Altogether, our data suggest that HIF-P4H-1 inhibition
      may be a promising therapeutic candidate for inflammatory diseases and cancer,
      enhancing the reciprocal negative regulation of the NF-kappaB and p53 pathways.

PMID- 29222482
TI  - Poly(methyl vinyl ether-alt-maleic acid) and ethyl monoester as building polymers
      for drug-loadable electrospun nanofibers.
AB  - New biomaterials are sought for the development of bioengineered nanostructures.
      In the present study, electrospun nanofibers have been synthesized by using
      poly(methyl vinyl ether-alt-maleic acid) and poly(methyl vinyl ether-alt-maleic
      ethyl monoester) (PMVEMA-Ac and PMVEMA-ES, respectively) as building polymers for
      the first time. To further functionalize these materials, nanofibers of PMVEMA-Ac
      and PMVEMA-ES containing a conjugated polyelectrolyte (HTMA-PFP, blue emitter,
      and HTMA-PFNT, red emitter) were achieved with both forms maintaining a high
      solid state fluorescence yield without altered morphology. Also, 5-aminolevulinic
      acid (5-ALA) was incorporated within these nanofibers, where it remained
      chemically stable. In all cases, nanofiber diameters were less than 150 nm as
      determined by scanning and transmission electron microscopy, and encapsulation
      efficiency of 5-ALA was 97 +/- 1% as measured by high-performance liquid
      chromatography. Both polymeric matrices showed rapid release kinetics in vertical
      cells (Franz cells) and followed Higuchi kinetics. In addition, no toxicity of
      nanofibers, in the absence of light, was found in HaCaT and SW480 cell lines.
      Finally, it was shown that loaded 5-ALA was functional, as it was internalized by
      cells in nanofiber-treated cultures and served as a substrate for the generation
      of protoporphyrin IX, suggesting these pharmaceutical vehicles are suitable for
      photodynamic therapy applications.

PMID- 29222483
TI  - Atlantic deep water provenance decoupled from atmospheric CO2 concentration
      during the lukewarm interglacials.
AB  - Ice core records show that atmospheric CO2 concentrations and Antarctic
      temperature were lower during the 'lukewarm interglacials' from 800 to 430 ka
      than the subsequent five interglacials. These different interglacial 'strengths'
      have been hypothesised to be controlled by Antarctic overturning circulation. How
      these variations in Antarctic overturning relate to Northern Atlantic overturning
      circulation, a major driver of Northern Hemisphere climate, is uncertain. Here we
      present a high-resolution record of authigenic neodymium isotopes-a water mass
      tracer that is independent of biological processes-and use it to reconstruct
      Atlantic overturning circulation during the last 800 kyr. This record reveals a
      similar proportion of North Atlantic Deep Water during the 'lukewarm
      interglacials' and the more recent interglacials. This observation suggests that
      the provenance of deep water in the Atlantic Ocean can be decoupled from
      ventilation state of the Southern Ocean and consequently the atmospheric
      concentration of carbon dioxide.

PMID- 29222484
TI  - Ground-state cooling of a mechanical oscillator in a hybrid optomechanical system
      including an atomic ensemble.
AB  - We investigate dynamical properties and the ground-state cooling of a mechanical
      oscillator in an optomechanical system coupling with an atomic ensemble. In this
      hybrid optomechanical system, an atomic ensemble which consists of two-level
      atoms couples with the cavity field. Here we consider the case where the atomic
      ensemble is in higher excitation. Studies show that the atom-field coupling
      strength can obviously influence the cooling process, and we can achieve the
      ground-state cooling of the mechanical oscillator by choosing the appropriate
      physical parameters of the system. Our cooling mechanism has potential
      applications in quantum information processing and procession measurement.

PMID- 29222485
TI  - Redox-switchable breathing behavior in tetrathiafulvalene-based metal-organic
      frameworks.
AB  - Metal-organic frameworks (MOFs) that respond to external stimuli such as guest
      molecules, temperature, or redox conditions are highly desirable. Herein, we
      coupled redox-switchable properties with breathing behavior induced by guest
      molecules in a single framework. Guided by topology, two flexible isomeric MOFs,
      compounds 1 and 2, with a formula of In(Me2NH2)(TTFTB), were constructed via a
      combination of [In(COO)4]- metal nodes and tetratopic tetrathiafulvalene-based
      linkers (TTFTB). The two compounds show different breathing behaviors upon the
      introduction of N2. Single-crystal X-ray diffraction, accompanied by molecular
      simulations, reveals that the breathing mechanism of 1 involves the bending of
      metal-ligand bonds and the sliding of interpenetrated frameworks, while 2
      undergoes simple distortion of linkers. Reversible oxidation and reduction of TTF
      moieties changes the linker flexibility, which in turn switches the breathing
      behavior of 2. The redox-switchable breathing behavior can potentially be applied
      to the design of stimuli-responsive MOFs.

PMID- 29222486
TI  - The Role of Personality and Subjective Exposure Experiences in Posttraumatic
      Stress Disorder and Depression Symptoms among Children Following Wenchuan
      Earthquake.
AB  - This study aims to investigate the role of personality traits and subjective
      exposure experiences in posttraumatic stress disorder and depression symptoms. In
      Qingchuan, 21,652 children aged 7 to 15 years were assessed using face-to-face
      interviews one year after the Wenchuan earthquake in China. The Junior Eysenck
      Personality Questionnaire, a modified earthquake exposure scale, the UCLA
      Posttraumatic Stress Disorder Reaction Index (adolescent), and the Adolescent
      Depression Inventory were used to assess personality characteristics, trauma
      experiences, posttraumatic stress disorder and depression symptoms, respectively.
      The measurement was completed with 20,749 children. After adjusting for other
      factors by multinomial logistic regression analysis, neuroticism, having felt
      unable to escape from the disaster and having been trapped for a longer time were
      risk factors of posttraumatic stress disorder and depression symptoms.
      Socialization was a protective factor of them. Having felt extreme panic or fear
      was a risk factor of posttraumatic stress disorder symptoms. For depression
      symptoms, introversion and psychoticism were risk factors, and extraversion was a
      protective factor. This study was conducted with the largest representative
      sample of child survivors of a natural, devastating disaster in a developing
      country. These results could be useful for planning psychological intervention
      strategies for children and for influencing further research.

PMID- 29222487
TI  - Structure-driven CO2 selectivity and gas capacity of ionic clathrate hydrates.
AB  - Ionic clathrate hydrates can selectively capture small gas molecules such as CO2,
      N2, CH4 and H2. We investigated CO2 + N2 mixed gas separation properties of ionic
      clathrate hydrates formed with tetra-n-butylammonium bromide (TBAB), tetra-n
      butylammonium chloride (TBAC), tetra-n-butylphosphonium bromide (TBPB) and tetra
      n-butylphosphonium chloride (TBPC). The results showed that CO2 selectivity of
      TBAC hydrates was remarkably higher than those of the other hydrates despite less
      gas capacity of TBAC hydrates. The TBAB hydrates also showed irregularly high CO2
      selectivity at a low pressure. X-ray diffraction and Raman spectroscopic analyses
      clarified that TBAC stably formed the tetragonal hydrate structure, and TBPB and
      TBPC formed the orthorhombic hydrate structure. The TBAB hydrates showed
      polymorphic phases which may consist of the both orthorhombic and tetragonal
      hydrate structures. These results showed that the tetragonal hydrate captured CO2
      more efficiently than the orthorhombic hydrate, while the orthorhombic hydrate
      has the largest gas capacity among the basic four structures of ionic clathrate
      hydrates. The present study suggests new potential for improving gas capacity and
      selectivity of ionic clathrate hydrates by choosing suitable ionic guest
      substances for guest gas components.

PMID- 29222488
TI  - Different carotenoid conformations have distinct functions in light-harvesting
      regulation in plants.
AB  - To avoid photodamage plants regulate the amount of excitation energy in the
      membrane at the level of the light-harvesting complexes (LHCs). It has been
      proposed that the energy absorbed in excess is dissipated via protein
      conformational changes of individual LHCs. However, the exact quenching mechanism
      remains unclear. Here we study the mechanism of quenching in LHCs that bind a
      single carotenoid species and are constitutively in a dissipative conformation.
      Via femtosecond spectroscopy we resolve a number of carotenoid dark states,
      demonstrating that the carotenoid is bound to the complex in different
      conformations. Some of those states act as excitation energy donors for the
      chlorophylls, whereas others act as quenchers. Via in silico analysis we show
      that structural changes of carotenoids are expected in the LHC protein domains
      exposed to the chloroplast lumen, where acidification triggers photoprotection in
      vivo. We propose that structural changes of LHCs control the conformation of the
      carotenoids, thus permitting access to different dark states responsible for
      either light harvesting or photoprotection.

PMID- 29222489
TI  - Specific binding of a polymer chain to a sequence of surface receptors.
AB  - This paper considers a biologically relevant question of a Gaussian chain (such
      as an unfolded protein) binding to a sequence of receptors with matching multiple
      ligands distributed along the chain. Using the characteristic time for a tethered
      ligand to bind to a surface receptor, we study the case of multiple binding to a
      linear sequence of receptors on the surface. The tethered binding time is
      determined by the entropic barrier for the chain to be stretched sufficiently to
      reach the distant receptor target, and a restriction on chain conformations near
      the substrate. Adsorption (multiple-site binding) is shown to be dominated by a
      simple zipper sequence, only occasionally accelerated by loop formation. However,
      when the number of receptors increases, a competing rate-limiting process takes
      over: the center of mass of the remaining free chain has to drift down the line
      of receptors, which takes longer when the receptors are close and the entropic
      pulling force is low. As a result, the time for the complete chain adsorption is
      minimised by a certain optimal number of receptors, depending on the distance to
      be traversed by the free end, and the chain length.

PMID- 29222491
TI  - Exploring biased attention towards body-related stimuli and its relationship with
      body awareness.
AB  - Stimuli of great social relevance exogenously capture attention. Here we explored
      the impact of body-related stimuli on endogenous attention. Additionally, we
      investigate the influence of internal states on biased attention towards this
      class of stimuli. Participants were presented with a body, face, or chair cue to
      hold in memory (Memory task) or to merely attend (Priming task) and,
      subsequently, they were asked to find a circle in an unrelated visual search
      task. In the valid condition, the circle was flanked by the cue. In the invalid
      condition, the pre-cued picture re-appeared flanking the distracter. In the
      neutral condition, the cue item did not re-appear in the search display. We found
      that although bodies and faces benefited from a general faster visual processing
      compared to chairs, holding them in memory did not produce any additional
      advantage on attention compared to when they are merely attended. Furthermore,
      face cues generated larger orienting effect compared to body and chairs cues in
      both Memory and Priming task. Importantly, results showed that individual
      sensitivity to internal bodily responses predicted the magnitude of the memory
      based orienting of attention to bodies, shedding new light on the relationship
      between body awareness and visuo-spatial attention.

PMID- 29222490
TI  - RAN translation at C9orf72-associated repeat expansions is selectively enhanced
      by the integrated stress response.
AB  - Repeat-associated non-AUG (RAN) translation allows for unconventional initiation
      at disease-causing repeat expansions. As RAN translation contributes to
      pathogenesis in multiple neurodegenerative disorders, determining its mechanistic
      underpinnings may inform therapeutic development. Here we analyze RAN translation
      at G4C2 repeat expansions that cause C9orf72-associated amyotrophic lateral
      sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause
      fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation
      initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start
      codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress
      response (ISR) activation. ISR-enhanced RAN translation requires an eIF2alpha
      phosphorylation-dependent alteration in start codon fidelity. In parallel, both
      CGG and G4C2 repeats trigger phosphorylated-eIF2alpha-dependent stress granule
      formation and global translational suppression. These findings support a model
      whereby repeat expansions elicit cellular stress conditions that favor RAN
      translation of toxic proteins, creating a potential feed-forward loop that
      contributes to neurodegeneration.

PMID- 29222492
TI  - Interaction of RNA-binding protein HuR and miR-466i regulates GM-CSF expression.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17
      (Th17) cells plays an essential role in autoimmune diseases. Transcriptional
      regulation of Th17 cell differentiation has been extensively studied, but post
      transcriptional regulation of Th17 cell differentiation has remained less well
      characterized. The RNA-binding protein HuR functions to promote the stability of
      target mRNAs via binding the AU-rich elements of the 3' untranslated region
      (3'UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and
      TNF-alpha. However, whether HuR regulates GM-CSF expression in Th17 cells has not
      been fully investigated. Here we showed that HuR conditional knockout (KO) Th17
      cells have decreased GM-CSF mRNA in comparison with wild-type (WT) Th17 cells,
      and that HuR binds directly to GM-CSF mRNA 3'UTR. Interestingly, HuR deficiency
      increased the levels of certain microRNA expression in Th17 cells; for example,
      miR-466i functioned to mediate GM-CSF and IL-17 mRNA decay, which was confirmed
      by in vitro luciferase assay. Furthermore, we found that HuR promoted Mxi1
      expression to inhibit certain miRNA expression. Taken together, these findings
      indicate that interaction of HuR and miR-466i orchestrates GM-CSF expression in
      Th17 cells.

PMID- 29222493
TI  - Bioinspired graphene membrane with temperature tunable channels for water gating
      and molecular separation.
AB  - Smart regulation of substance permeability through porous membranes is highly
      desirable for membrane applications. Inspired by the stomatal closure feature of
      plant leaves at relatively high temperature, here we report a nano-gating
      membrane with a negative temperature-response coefficient that is capable of
      tunable water gating and precise small molecule separation. The membrane is
      composed of poly(N-isopropylacrylamide) covalently bound to graphene oxide via
      free-radical polymerization. By virtue of the temperature tunable lamellar spaces
      of the graphene oxide nanosheets, the water permeance of the membrane could be
      reversibly regulated with a high gating ratio. Moreover, the space tunability
      endows the membrane with the capability of gradually separating multiple
      molecules of different sizes. This nano-gating membrane expands the scope of
      temperature-responsive membranes and has great potential applications in smart
      gating systems and molecular separation.

PMID- 29222494
TI  - The consequences of replacing wildlife with livestock in Africa.
AB  - The extirpation of native wildlife species and widespread establishment of
      livestock farming has dramatically distorted large mammal herbivore communities
      across the globe. Ecological theory suggests that these shifts in the form and
      the intensity of herbivory have had substantial impacts on a range of ecosystem
      processes, but for most ecosystems it is impossible to quantify these changes
      accurately. We address these challenges using species-level biomass data from sub
      Saharan Africa for both present day and reconstructed historical herbivore
      communities. Our analyses reveal pronounced herbivore biomass losses in wetter
      areas and substantial biomass increases and functional type turnover in arid
      regions. Fire prevalence is likely to have been altered over vast areas where
      grazer biomass has transitioned to above or below the threshold at which grass
      fuel reduction can suppress fire. Overall, shifts in the functional composition
      of herbivore communities promote an expansion of woody cover. Total herbivore
      methane emissions have more than doubled, but lateral nutrient diffusion capacity
      is below 5% of past levels. The release of fundamental ecological constraints on
      herbivore communities in arid regions appears to pose greater threats to
      ecosystem function than do biomass losses in mesic regions, where fire remains
      the major consumer.

PMID- 29222495
TI  - Effect of the preparation of lime putties on their properties.
AB  - In the study of lime as the basic component of historical mortars and plasters,
      four lime putties prepared from various kinds of lime of various granulometry and
      by various ways of preparation were evaluated. The rheological properties and
      micro-morphologic changes, growing of calcite crystals, and rate of carbonation
      were monitored. The lime putty prepared from lump lime achieves the best
      rheological properties, yield stress 214.7 Pa and plastic viscosity 2.6 Pa.s. The
      suitability of this lime putty was checked by testing the development of calcium
      hydroxide and calcite crystals using scanning electron microscopy and
      environmental scanning electron microscopy. The disordered crystals of calcium
      hydroxide exhibit better carbonation resulting in the large crystals of calcite;
      therefore, the mortar prepared from the lump lime has the highest flexural
      strength and compressive strength 0.8/2.5 MPa, its carbonation is the fastest and
      exhibits the longest durability. Also, thanks to the micro-morphological
      characterization of samples in their native state by means of environmental
      scanning electron microscopy, the new way of lime putty preparation by mixing was
      proven. The preparation consists in the mechanical crash of the lime particles
      immediately after hydration. This enables the properties of putty prepared from
      lump lime to be nearly reached.

PMID- 29222496
TI  - Genome-wide and gene-based association mapping for rice eating and cooking
      characteristics and protein content.
AB  - Rice eating and cooking quality and protein content (PC) are important properties
      affecting consumers' preferences, nutrition and health. Linkage QTL mapping and
      association studies are usually applied to genetically dissect related traits,
      which could be further facilitated by high density SNP markers and gene
      annotation based on reference genome to rapid identify candidate genes associated
      with interested traits. Here, we carried out an association study for apparent
      amylose content (AC), gel consistency (GC), gelatinization temperature (GT) and
      PC evaluated in two environments using a diverse panel of 258 accessions from 3 K
      Rice Genome Project. Wide phenotypic variations were observed in this panel.
      Genome-wide association study using 22,488 high quality SNPs identified 19 QTL
      affecting the four traits. Combining gene-based association study and haplotype
      analyses plus functional annotation allowed us to shortlist nine candidate genes
      for four important QTL regions affecting AC, GC and GT, including two cloned
      genes (Wx and ALK), and seven novels. The research suggested that GWAS and gene
      based association analysis followed by haplotype analysis is an effective way to
      detect candidate genes. The identified genes and QTL provided valuable sources
      for future functional characterization and genetic improvement of rice eating and
      cooking quality and PC.

PMID- 29222497
TI  - Computational insights for the hydride transfer and distinctive roles of key
      residues in cholesterol oxidase.
AB  - Cholesterol oxidase (ChOx), a member of the glucose-methanol-choline (GMC)
      family, catalyzes the oxidation of the substrate via a hydride transfer mechanism
      and concomitant reduction of the FAD cofactor. Unlike other GMC enzymes, the
      conserved His447 is not the catalytic base that deprotonates the substrate in
      ChOx. Our QM/MM MD simulations indicate that the Glu361 residue acts as a
      catalytic base facilitating the hydride transfer from the substrate to the
      cofactor. We find that two rationally chosen point mutations (His447Gln and
      His447Asn) cause notable decreases in the catalytic activity. The binding free
      energy calculations show that the Glu361 and His447 residues are important in
      substrate binding. We also performed high-level double-hybrid density functional
      theory simulations using small model systems, which support the QM/MM MD results.
      Our work provides a basis for unraveling the substrate oxidation mechanism in GMC
      enzymes in which the conserved histidine does not act as a base.

PMID- 29222498
TI  - Author Correction: Charles D. Surh 1960-2017.
AB  - In the version of this article initially published, the year of birth provided
      (1960) was incorrect. The correct year is 1961. The error has been corrected in
      the HTML and PDF versions of the article.

PMID- 29222499
TI  - Crystal structure of an RNA-cleaving DNAzyme.
AB  - In addition to storage of genetic information, DNA can also catalyze various
      reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest,
      and they can cleave RNAs in a sequence-specific manner. Owing to their great
      potential in medical therapeutics, virus control, and gene silencing for disease
      treatments, RNA-cleaving DNAzymes have been extensively studied; however, the
      mechanistic understandings of their substrate recognition and catalysis remain
      elusive. Here, we report three catalytic form 8-17 DNAzyme crystal structures. 8
      17 DNAzyme adopts a V-shape fold, and the Pb2+ cofactor is bound at the pre
      organized pocket. The structures with Pb2+ and the modification at the cleavage
      site captured the pre-catalytic state of the RNA cleavage reaction, illustrating
      the unexpected Pb2+-accelerated catalysis, intrinsic tertiary interactions, and
      molecular kink at the active site. Our studies reveal that DNA is capable of
      forming a compacted structure and that the functionality-limited bio-polymer can
      have a novel solution for a functional need in catalysis.

PMID- 29222500
TI  - Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection.
AB  - Patients who survive influenza A (H7N9) virus infection are at risk of physical
      and psychological complications of lung injury and multi-organ dysfunction.
      However, there were no prospectively individualized assessments of physiological,
      functional and quality-of-life measures after hospital discharge. The current
      study aims to assess the main determinants of functional disability of these
      patients during the follow-up. Fifty-six influenza A (H7N9) survivors were
      investigated during the 2-year after discharge from the hospital. Results show
      interstitial change and fibrosis on pulmonary imaging remained 6 months after
      hospital discharge. Both ventilation and diffusion dysfunction improved, but
      restrictive and obstructive patterns on ventilation function test persisted
      throughout the follow-up period. For patients with acute respiratory distress
      syndrome lung functions improved faster during the first six months. Role
      physical and Role-emotional domains in the 36-Item Short-Form Health Survey were
      worse than those of a sex- and age-matched general population group. The quality
      of life of survivors with ARDS was lower than those with no ARDS. Our findings
      suggest that pulmonary function and imaging findings improved during the first 6
      months especially for those with ARDS, however long-term lung disability and
      psychological impairment in H7N9 survivors persisted at 2 years after discharge
      from the hospital.

PMID- 29222501
TI  - Inversion evolutionary rates might limit the experimental identification of
      inversion breakpoints in non-model species.
AB  - Chromosomal inversions are structural changes that alter gene order but generally
      not gene content in the affected region. In Drosophila, extensive cytological
      studies revealed the widespread character of inversion polymorphism, with
      evidence for its adaptive character. In Drosophila subobscura, polymorphism
      affects both its four large autosomal elements and its X (A) chromosome. The
      characterization of eight of these autosomal inversions breakpoints revealed that
      most of them originated through the staggered-breaks mechanism. Here, we have
      performed chromosomal walks to identify the breakpoints of two X-chromosome
      widely distributed inversions -A2 and A1- of D. subobscura. Inversion A2 is
      considered a warm-adapted arrangement that exhibits parallel latitudinal clines
      in the species ancestral distribution area and in both American subcontinents,
      whereas inversion A1 is only present in the Palearctic region where it presents
      an east-west cline. The duplication detected at the A2 inversion breakpoints is
      consistent with its origin by the staggered-breaks mechanism. Inversion A1
      breakpoints could not be molecularly identified even though they could be
      narrowly delimited. This result points to chromosome walking limitations when
      using as a guide the genome of other species. Limitations stem from the rate of
      evolution by paracentric inversions, which in Drosophila is highest for the X
      chromosome.

PMID- 29222502
TI  - Pharmacokinetics, biodistribution and brain retention of a bispecific antibody
      based PET radioligand for imaging of amyloid-beta.
AB  - Monoclonal antibodies (mAbs) have not been used as positron emission tomography
      (PET) ligands for in vivo imaging of the brain because of their limited passage
      across the blood-brain barrier (BBB). However, due to their high affinity and
      specificity, mAbs may be an attractive option for brain PET if their brain
      distribution can be facilitated. In the present study, a F(ab')2 fragment of the
      amyloid-beta (Abeta) protofibril selective mAb158 was chemically conjugated to
      the transferrin receptor (TfR) antibody 8D3 to enable TfR mediated transcytosis
      across the BBB. The generated bispecific protein, 8D3-F(ab')2-h158, was
      subsequently radiolabeled and used for microPET imaging of Abeta pathology in two
      mouse models of AD. [124I]8D3-F(ab')2-h158 was distributed across the BBB several
      fold more than unmodified mAbs in general and its accumulation in the brain
      reflected disease progression, while its concentration in blood and other organs
      remained stable across all age groups studied. Cerebellum was largely devoid of
      8D3-F(ab')2-h158 in young and middle aged mice, while mice older than 18 months
      also showed some accumulation in cerebellum. In a longer perspective, the use of
      bispecific antibodies as PET ligands may enable in vivo 'immunohistochemistry'
      also of other proteins in the brain for which PET radioligands are lacking.

PMID- 29222503
TI  - CO2 Mineralization and Utilization using Steel Slag for Establishing a Waste-to
      Resource Supply Chain.
AB  - Both steelmaking via an electric arc furnace and manufacturing of portland cement
      are energy-intensive and resource-exploiting processes, with great amounts of
      carbon dioxide (CO2) emission and alkaline solid waste generation. In fact, most
      CO2 capture and storage technologies are currently too expensive to be widely
      applied in industries. Moreover, proper stabilization prior to utilization of
      electric arc furnace slag are still challenging due to its high alkalinity, heavy
      metal leaching potentials and volume instability. Here we deploy an integrated
      approach to mineralizing flue gas CO2 using electric arc furnace slag while
      utilizing the reacted product as supplementary cementitious materials to
      establish a waste-to-resource supply chain toward a circular economy. We found
      that the flue gas CO2 was rapidly mineralized into calcite precipitates using
      electric arc furnace slag. The carbonated slag can be successfully utilized as
      green construction materials in blended cement mortar. By this modulus, the
      global CO2 reduction potential using iron and steel slags was estimated to be
      ~138 million tons per year.

PMID- 29222504
TI  - RNAStructuromeDB: A genome-wide database for RNA structural inference.
AB  - RNA plays important roles in almost every aspect of biology, and every aspect of
      RNA biology is influenced by its folding. This is a particularly important
      consideration in the era of high-throughput sequencing, when the discovery of
      novel transcripts far outpaces our knowledge of their functions. To gain a
      comprehensive picture of biology requires a structural framework for making
      functional inferences on RNA. To this end we have developed the RNA Structurome
      Database ( https://structurome.bb.iastate.edu ), a comprehensive repository of
      RNA secondary structural information that spans the entire human genome. Here, we
      compile folding information for every base pair of the genome that may be
      transcribed: coding, noncoding, and intergenic regions, as well as repetitive
      elements, telomeres, etc. This was done by fragmenting the GRCh38 reference
      genome into 154,414,320 overlapping sequence fragments and, for each fragment,
      calculating a set of metrics based on the sequence's folding properties. These
      data will facilitate a wide array of investigations: e.g. discovery of structured
      regulatory elements in differential gene expression data or noncoding RNA
      discovery, as well as allow genome-scale analyses of RNA folding.

PMID- 29222505
TI  - A comparison of methods to measure central and peripheral oxytocin concentrations
      in human and non-human primates.
AB  - Oxytocin (OT) concentration in the blood is considered to be a marker of its
      action in the brain. However, two problems have emerged when measuring OT level
      in the blood. First, it is unclear whether different methods of assessment lead
      to similar OT values. Second, it is unclear if plasma OT concentrations is
      informative on what OT does in the brain. To clarify these issues, we collected
      cerebrospinal fluid (CSF) from the brain ventricle of 25 patients during surgery
      to compare with plasma OT after simultaneous blood withdrawal. Additionally, we
      collected 12 CSF and blood samples from non-human primates while awake or under
      anaesthesia. We used four methods to assay OT concentrations: Commercial EIA
      with/without extraction, laboratory developed EIA with filtration and RIA with
      extraction. Three of these methods showed a positive correlation between plasma
      and CSF OT, suggesting a link between plasma and central OT, at least under
      specific testing conditions. However, none of the methods correlated to each
      other. Our results show major disagreements among methods used here to measure
      peripheral and brain OT and therefore they call for more caution when plasma OT
      is taken as a marker of central OT.

PMID- 29222506
TI  - An assessment of the global impact of 21st century land use change on soil
      erosion.
AB  - Human activity and related land use change are the primary cause of accelerated
      soil erosion, which has substantial implications for nutrient and carbon cycling,
      land productivity and in turn, worldwide socio-economic conditions. Here we
      present an unprecedentedly high resolution (250 * 250 m) global potential soil
      erosion model, using a combination of remote sensing, GIS modelling and census
      data. We challenge the previous annual soil erosion reference values as our
      estimate, of 35.9 Pg yr-1 of soil eroded in 2012, is at least two times lower.
      Moreover, we estimate the spatial and temporal effects of land use change between
      2001 and 2012 and the potential offset of the global application of conservation
      practices. Our findings indicate a potential overall increase in global soil
      erosion driven by cropland expansion. The greatest increases are predicted to
      occur in Sub-Saharan Africa, South America and Southeast Asia. The least
      developed economies have been found to experience the highest estimates of soil
      erosion rates.

PMID- 29222507
TI  - Induced unconventional superconductivity on the surface states of Bi2Te3
      topological insulator.
AB  - Topological superconductivity is central to a variety of novel phenomena
      involving the interplay between topologically ordered phases and broken-symmetry
      states. The key ingredient is an unconventional order parameter, with an orbital
      component containing a chiral p x  + ip y wave term. Here we present phase
      sensitive measurements, based on the quantum interference in nanoscale Josephson
      junctions, realized by using Bi2Te3 topological insulator. We demonstrate that
      the induced superconductivity is unconventional and consistent with a sign
      changing order parameter, such as a chiral p x  + ip y component. The magnetic
      field pattern of the junctions shows a dip at zero externally applied magnetic
      field, which is an incontrovertible signature of the simultaneous existence of 0
      and pi coupling within the junction, inherent to a non trivial order parameter
      phase. The nano-textured morphology of the Bi2Te3 flakes, and the dramatic role
      played by thermal strain are the surprising key factors for the display of an
      unconventional induced order parameter.

PMID- 29222509
TI  - Impact of model calibration on cost-effectiveness analysis of cervical cancer
      prevention.
AB  - Markov chain models are commonly used to simulate the natural history of human
      papillomavirus infection and subsequent cervical lesions with the aim of
      predicting future benefits of health interventions. Developing and calibrating
      these models entails making a number of critical decisions that will influence
      the ability of the model to reflect real conditions and predict future
      situations. Accuracy of selected inputs and calibration procedures are two of the
      crucial aspects for model performance and understanding their influence is
      essential, especially when involves policy decisions. The aim of this work is to
      assess the health and economic impact on cervical cancer prevention strategies
      currently under discussion according to the most common methods of model
      calibration combined with different accuracy degree of initial inputs. Model
      results show large differences on the goodness of fit and cost-effectiveness
      outcomes depending on the calibration approach used, and these variations may
      affect health policy decisions. Our findings strengthen the importance of
      obtaining good calibrated probability matrices to get reliable health and cost
      outcomes, and are directly generalizable to any cost-effectiveness analysis based
      on Markov chain models.

PMID- 29222508
TI  - CRISPR-Cpf1 mediates efficient homology-directed repair and temperature
      controlled genome editing.
AB  - Cpf1 is a novel class of CRISPR-Cas DNA endonucleases, with a wide range of
      activity across different eukaryotic systems. Yet, the underlying determinants of
      this variability are poorly understood. Here, we demonstrate that LbCpf1, but not
      AsCpf1, ribonucleoprotein complexes allow efficient mutagenesis in zebrafish and
      Xenopus. We show that temperature modulates Cpf1 activity by controlling its
      ability to access genomic DNA. This effect is stronger on AsCpf1, explaining its
      lower efficiency in ectothermic organisms. We capitalize on this property to show
      that temporal control of the temperature allows post-translational modulation of
      Cpf1-mediated genome editing. Finally, we determine that LbCpf1 significantly
      increases homology-directed repair in zebrafish, improving current approaches for
      targeted DNA integration in the genome. Together, we provide a molecular
      understanding of Cpf1 activity in vivo and establish Cpf1 as an efficient and
      inducible genome engineering tool across ectothermic species.

PMID- 29222510
TI  - Semiconductor SERS enhancement enabled by oxygen incorporation.
AB  - Semiconductor-based surface-enhanced Raman spectroscopy (SERS) substrates
      represent a new frontier in the field of SERS. However, the application of
      semiconductor materials as SERS substrates is still seriously impeded by their
      low SERS enhancement and inferior detection sensitivity, especially for non-metal
      oxide semiconductor materials. Herein, we demonstrate a general oxygen
      incorporation-assisted strategy to magnify the semiconductor substrate-analyte
      molecule interaction, leading to significant increase in SERS enhancement for non
      metal-oxide semiconductor materials. Oxygen incorporation in MoS2 even with trace
      concentrations can not only increase enhancement factors by up to 100,000-fold
      compared with oxygen-unincorporated samples but also endow MoS2 with low limit of
      detection below 10-7 M. Intriguingly, combined with the findings in previous
      studies, our present results indicate that both oxygen incorporation and
      extraction processes can result in SERS enhancement, probably due to the enhanced
      charge-transfer resonance as well as exciton resonance arising from the judicious
      control of oxygen admission in semiconductor substrate.

PMID- 29222511
TI  - Dynamics of Transformation from Platinum Icosahedral Nanoparticles to Larger FCC
      Crystal at Millisecond Time Resolution.
AB  - Atomic motion at grain boundaries is essential to microstructure development,
      growth and stability of catalysts and other nanostructured materials. However,
      boundary atomic motion is often too fast to observe in a conventional
      transmission electron microscope (TEM) and too slow for ultrafast electron
      microscopy. Here, we report on the entire transformation process of strained Pt
      icosahedral nanoparticles (ICNPs) into larger FCC crystals, captured at 2.5 ms
      time resolution using a fast electron camera. Results show slow diffusive
      dislocation motion at nm/s inside ICNPs and fast surface transformation at MUm/s.
      By characterizing nanoparticle strain, we show that the fast transformation is
      driven by inhomogeneous surface stress. And interaction with pre-existing defects
      led to the slowdown of the transformation front inside the nanoparticles.
      Particle coalescence, assisted by oxygen-induced surface migration at T >= 300 
      degrees C, also played a critical role. Thus by studying transformation in the Pt
      ICNPs at high time and spatial resolution, we obtain critical insights into the
      transformation mechanisms in strained Pt nanoparticles.

PMID- 29222512
TI  - Improving Gene Regulatory Network Inference by Incorporating Rates of
      Transcriptional Changes.
AB  - Organisms respond to changes in their environment through transcriptional
      regulatory networks (TRNs). The regulatory hierarchy of these networks can be
      inferred from expression data. Computational approaches to identify TRNs can be
      applied in any species where quality RNA can be acquired, However, ChIP-Seq and
      similar validation methods are challenging to employ in non-model species.
      Improving the accuracy of computational inference methods can significantly
      reduce the cost and time of subsequent validation experiments. We have developed
      ExRANGES, an approach that improves the ability to computationally infer TRN from
      time series expression data. ExRANGES utilizes both the rate of change in
      expression and the absolute expression level to identify TRN connections. We
      evaluated ExRANGES in five data sets from different model systems. ExRANGES
      improved the identification of experimentally validated transcription factor
      targets for all species tested, even in unevenly spaced and sparse data sets.
      This improved ability to predict known regulator-target relationships enhances
      the utility of network inference approaches in non-model species where
      experimental validation is challenging. We integrated ExRANGES with two different
      network construction approaches and it has been implemented as an R package
      available here: http://github.com/DohertyLab/ExRANGES . To install the package
      type: devtools::install_github("DohertyLab/ExRANGES").

PMID- 29222513
TI  - Biotrophy-necrotrophy switch in pathogen evoke differential response in resistant
      and susceptible sesame involving multiple signaling pathways at different phases.
AB  - Infection stages of charcoal rot fungus Macrophomina phaseolina in sesame
      revealed for the first time a transition from biotrophy via BNS (biotrophy-to
      necrotrophy switch) to necrotrophy as confirmed by transcriptional studies.
      Microscopy using normal and GFP-expressing pathogen showed typical constricted
      thick intercellular bitrophic hyphae which gave rise to thin intracellular
      necrotrophic hyphae during BNS and this stage was delayed in a resistant host.
      Results also show that as the pathogen switched its strategy of infection, the
      host tailored its defense strategy to meet the changing situation. Less ROS
      accumulation, upregulation of ROS signaling genes and higher antioxidant enzyme
      activities post BNS resulted in resistance. There was greater accumulation of
      secondary metabolites and upregulation of secondary metabolite-related genes
      after BNS. A total of twenty genes functioning in different aspects of plant
      defense that were monitored over a time course during the changing infection
      phases showed a coordinated response. Experiments using phytohormone priming and
      phytohormone inhibitors showed that resistance resulted from activation of JA-ET
      signaling pathway. Most importantly this defense response was more prompt in the
      resistant than the susceptible host indicating that a resistant host makes
      different choices from a susceptible host during infection which ultimately
      influences the severity of the disease.

PMID- 29222514
TI  - Indium phosphide metasurface with enhanced nonlinear absorption.
AB  - We solve the nonlinear Maxwell equations in an InP-based dielectric metamaterial,
      considering both two-photon absorption and photo-induced free-carrier absorption.
      We obtain the intensity-dependent reflection, absorption, and effective
      permittivity and permeability of the metamaterial. Our results show that
      nonlinear absorption dampens both the electric and magnetic Mie resonance,
      although the magnetic resonance is more affected because it occurs at longer
      wavelengths where the free-carrier absorption cross section is larger. Owing to
      field concentration in the metamaterial at resonance, the threshold intensity for
      nonlinear absorption is reduced by a factor of about 30 compared to a homogeneous
      layer of the same thickness. Our results have implications on the use of
      dielectric metamaterials for nonlinear applications such as higher harmonic
      generation, optical limiting, and ultrafast modulation.

PMID- 29222515
TI  - The highly efficient photocatalytic and light harvesting property of Ag-TiO2 with
      negative nano-holes structure inspired from cicada wings.
AB  - The negative replica of biomorphic TiO2 with nano-holes structure has been
      effectively fabricated directly from nano-nipple arrays structure of cicada wings
      by using a simple, low-cost and highly effective sol-gel ultrasonic method. The
      nano-holes array structure was well maintained after calcination in air at 500 
      degrees C. The Ag nanoparticles (10 nm-25 nm) were homogeneously decorated on the
      surface and to the side wall of nano-holes structure. It was observed that the
      biomorphic Ag-TiO2 showed remarkable photocatalytic activity by degradation of
      methyl blue (MB) under UV-vis light irradiation. The biomorphic Ag-TiO2 with nano
      holes structure showed superior photocatalytic activity compared to the
      biomorphic TiO2 and commercial Degussa P25. This high-performance photocatalytic
      activity of the biomorphic Ag-TiO2 may be attributed to the nano-holes structure,
      localized surface plasmon resonance (LSPR) property of the Ag nanoparticles, and
      enhanced electron-hole separation. Moreover, the biomorphic Ag-TiO2 showed more
      absorption capability in the visible wavelength range. This work provides a new
      insight to design such a structure which may lead to a range of novel
      applications.

PMID- 29222516
TI  - Impact of self-esteem and sex on stress reactions.
AB  - Positive self-evaluation is a major psychological resource modulating stress
      coping behavior. Sex differences have been reported in self-esteem as well as
      stress reactions, but so far their interactions have not been investigated.
      Therefore, we investigated sex-specific associations of self-esteem and stress
      reaction on behavioral, hormonal and neural levels. We applied a commonly used
      fMRI-stress task in 80 healthy participants. Men compared to women showed higher
      activation during stress in hippocampus, precuneus, superior temporal gyrus (STG)
      and insula. Furthermore, men outperformed women in the stress task and had higher
      cortisol and testosterone levels than women after stress. Self-esteem had an
      impact on precuneus, insula and STG activation during stress across the whole
      group. During stress, men recruit regions associated with emotion and stress
      regulation, self-referential processing and cognitive control more strongly than
      women. Self-esteem affects stress processing, however in a sex-independent
      fashion: participants with lower self-esteem show higher activation of regions
      involved in emotion and stress regulation, self-referential processing and
      cognitive control. Taken together, our data suggest that men are more engaged
      during the applied stress task. Across women and men, lower self-esteem increases
      the effort in emotion and stress processing and cognitive control, possibly
      leading to self-related thoughts in stressful situations.

PMID- 29222518
TI  - Interplay between geo-population factors and hierarchy of cities in multilayer
      urban networks.
AB  - Only taking into consideration the interplay between processes occurring at
      different levels of a country can provide the complete social and geopolitical
      plot of its urban system. We study the interaction of the administrative
      structure and the geographical connectivity between cities with the help of a
      multiplex network approach. We found that a spatially-distributed geo-network
      imposes its own ranking to the hierarchical administrative network, while the
      latter redistributes the shortest paths between nodes in the geographical layer.
      Using both real demographic data of population censuses of the Republic of
      Kazakhstan and theoretical models, we show that in a country-scale urban network
      and for each specific city, the geographical neighbouring with highly populated
      areas is more important than its political setting. Furthermore, the structure of
      political subordination is instead crucial for the wealth of transportation
      network and communication between populated regions of the country.

PMID- 29222517
TI  - Input-dependent regulation of excitability controls dendritic maturation in
      somatosensory thalamocortical neurons.
AB  - Input from the sensory organs is required to pattern neurons into topographical
      maps during development. Dendritic complexity critically determines this
      patterning process; yet, how signals from the periphery act to control dendritic
      maturation is unclear. Here, using genetic and surgical manipulations of sensory
      input in mouse somatosensory thalamocortical neurons, we show that membrane
      excitability is a critical component of dendritic development. Using a
      combination of genetic approaches, we find that ablation of N-methyl-D-aspartate
      (NMDA) receptors during postnatal development leads to epigenetic repression of
      Kv1.1-type potassium channels, increased excitability, and impaired dendritic
      maturation. Lesions to whisker input pathways had similar effects. Overexpression
      of Kv1.1 was sufficient to enable dendritic maturation in the absence of sensory
      input. Thus, Kv1.1 acts to tune neuronal excitability and maintain it within a
      physiological range, allowing dendritic maturation to proceed. Together, these
      results reveal an input-dependent control over neuronal excitability and
      dendritic complexity in the development and plasticity of sensory pathways.

PMID- 29222519
TI  - Virtual screening for inhibitors of the human TSLP:TSLPR interaction.
AB  - The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal
      role in the pathophysiology of various allergy disorders that are mediated by
      type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP
      forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7
      receptor subunit alpha (IL-7Ralpha), thereby activating a signaling cascade that
      culminates in the release of pro-inflammatory mediators. In this study, we
      conducted an in silico characterization of the TSLP:TSLPR complex to investigate
      the drugability of this complex. Two commercially available fragment libraries
      were screened computationally for possible inhibitors and a selection of
      fragments was subsequently tested in vitro. The screening setup consisted of two
      orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a
      biochemical assay based on a TSLP:alkaline phosphatase fusion protein. Four
      fragments pertaining to diverse chemical classes were identified to reduce
      TSLP:TSLPR complex formation to less than 75% in millimolar concentrations. We
      have used unbiased molecular dynamics simulations to develop a Markov state model
      that characterized the binding pathway of the most interesting compound. This
      work provides a proof-of-principle for use of fragments in the inhibition of
      TSLP:TSLPR complexation.

PMID- 29222520
TI  - Smoking and alcohol drinking in relation to the risk of esophageal squamous cell
      carcinoma: A population-based case-control study in China.
AB  - Previous results regarding the associations between esophageal squamous-cell
      carcinoma (ESCC) risk and smoking/alcohol drinking in high-risk areas are
      inconsistent. We performed a large population-based case-control study from 2010
      to 2013 in a high-incidence area of China, and enrolled 1353 ESCC cases and 1961
      controls. Data regarding smoking and alcohol drinking were collected via face-to
      face interviews using a structured questionnaire. Odd ratios (ORs) with 95%
      confidence intervals (CIs) were estimated using unconditional logistic regression
      models. After adjusting for alcohol drinking and other potential confounders,
      male heavy smokers (i.e., those who started smoked more than 20 cigarettes per
      day or 40 pack-years, or started smoking early), showed a moderately increased
      risk for ESCC; however, current smoking was not associated with an increased
      risk. Alcohol drinking among males significantly increased the risk for ESCC (OR
      = 2.20, 95%CI:1.79~2.70). We observed increasing excess ESCC risks with
      decreasing age at behavior initiation as well as with increasing duration and
      intensity of alcohol intake, which were particularly evident among current
      smokers. In contrast, neither smoking nor alcohol drinking was not associated
      with ESCC risk among females. In conclusion, alcohol drinking shows a monotonic
      dose-response relationship with ESCC risk among men, and this relationship is
      particularly evident among smokers.

PMID- 29222521
TI  - Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for
      asymptomatic Leishmania infantum and Leishmania donovani infection.
AB  - Whole blood stimulation with soluble Leishmania antigen (SLA), followed by plasma
      cytokine and chemokine determination, provides means of detecting subjects with
      asymptomatic Leishmania infection. This work examines the potential of Protein
      Saver 903 cards for the storage and transport of SLA-stimulated dried plasma spot
      samples. Blood was collected from asymptomatic and negative control subjects
      living in a Leishmania infantum- (Spain) and Leishmania donovani-endemic area
      (Bangladesh). After SLA-stimulation, three types of sample were prepared: frozen
      liquid plasma (-20  degrees C), and plasma dropped onto Protein Saver cards kept
      at -20  degrees C (DPS-FZ), and at ambient temperature (DPS-AT). The
      concentrations of IFN-gamma, IL-2, CXCL10, CXCL9, CCL2 and CXCL8 in the thawed
      liquid plasma (TLP), DPS-FZ and DPS-AT samples were then determined. Strong
      correlations were seen between the TLP and DPS-FZ/AT samples for all the studied
      cytokines/chemokines in both the L. infantum and L. donovani areas. Protein Saver
      903 cards would therefore appear to allow for the transport of SLA-stimulated
      plasma samples by courier at ambient temperature. The CXCL10 and CXCL9 detectable
      in these plasma spots provided robust markers for identifying asymptomatic
      subjects from both endemic areas. This easy procedure opens up new possibilities
      for field studies in resource-limited settings, which could help in Leishmania
      control.

PMID- 29222522
TI  - A new method to evaluate floodwater for control/use in high-sediment rivers of
      Northwest China.
AB  - Evaluating the quantity of flood season floodwater that is difficult to control
      or use in rivers with high sediment concentration is an important part of water
      resource evaluation and floodwater resource utilisation. This study proposes a
      method coupling water quantity and quality to evaluate such floodwater. The
      method divides floodwater into floodwater that is difficult to control
      ('difficult-controllable') and floodwater that is controllable but difficult to
      use ('controllable but difficult-use'). A case study of the Bajiazui Reservoir in
      the Jing River in China's Loess Plateau is presented. The average annual quantity
      of difficult-controllable floodwater is 10.4 million m3. The annual mean quantity
      of the difficult-controllable/-use floodwater is 38.1 million m3. The majority of
      that amount (78.21%) comprised controllable but difficult-use floodwater. An
      analysis of 64 combinations of factors influencing the quantity of the difficult
      controllable/-use floodwater shows that the sediment concentration of run-off is
      the primary factor influencing the difficult-controllable/-use floodwater. The
      reservoir's maximum flood release capacity and floodwater rejection coefficient
      are the primary factors affecting the difficult-controllable and controllable but
      difficult-use floodwater, respectively. The new evaluation method is superior to
      traditional methods and is suitable for evaluating difficult-controllable/-use
      floodwater in high-sediment rivers.

PMID- 29222523
TI  - Optimization of cotton variety registration criteria aided with a genotype-by
      trait biplot analysis.
AB  - China is one of the largest cotton producing countries in the world thanks to
      high yields, on which a variety registration system has mainly focused, so that a
      lack of quality is nowadays acknowledged as a weak point of the cotton industry
      in that country. The objective of this study was to check the hypothesis that
      bias in cultivar selection in favor of yield has been maintained through the
      application of an imperfect selection index (SI), but that a better outcome is
      possible. Our demonstration is based on an analysis of the data from ten years of
      cotton variety trials using genotype-by-trait biplots, implemented both for the
      cultivar selection index (SI) currently applied in China and for an adjusted
      selection index (ASI) that more effectively took into account the antagonism
      between yield and quality traits. The main findings were: 1) significant negative
      associations between yield and fiber quality hindered their simultaneous
      improvement; 2) registered genotypes were mainly determined by the SI which was
      primarily yield-oriented; 3) no progress in fiber quality was recorded unlike
      yield; 4) balanced progress in yield and quality is possible through an adjusted
      selection index (ASI) guided by genotype-by-trait biplot analysis.

PMID- 29222524
TI  - Andean mountain building and magmatic arc migration driven by subduction-induced
      whole mantle flow.
AB  - Subduction along the western margin of South America has been active since the
      Jurassic, but Andean orogeny started in the middle Cretaceous and was preceded by
      backarc extension in the Jurassic-Early Cretaceous. The timing and sequence of
      these events has remained unexplained. Here I present a four-dimensional buoyancy
      driven whole-mantle subduction model implying that the ~200 Myr geological
      evolution can be attributed to sinking of a wide slab into a layered mantle,
      where upper-mantle wide-slab subduction causes backarc extension, while whole
      mantle (upper+lower) wide-slab subduction drives Andean orogeny. The model
      reproduces the maximum shortening and crustal thickness observed in the Central
      Andes and their progressive northward and southward decrease. The subduction
      evolution coincides with a 29 degrees  decrease in slab dip angle, explaining
      ~200 km of Jurassic-present eastward migration of the Central Andean magmatic
      arc. Such arc migration negates proposed long-term subduction erosion and
      continental destruction, but is consistent with long-term crustal growth.

PMID- 29222526
TI  - Numerical value biases sound localization.
AB  - Speech recognition starts with representations of basic acoustic perceptual
      features and ends by categorizing the sound based on long-term memory for word
      meaning. However, little is known about whether the reverse pattern of lexical
      influences on basic perception can occur. We tested for a lexical influence on
      auditory spatial perception by having subjects make spatial judgments of number
      stimuli. Four experiments used pointing or left/right 2-alternative forced choice
      tasks to examine perceptual judgments of sound location as a function of digit
      magnitude (1-9). The main finding was that for stimuli presented near the median
      plane there was a linear left-to-right bias for localizing smaller-to-larger
      numbers. At lateral locations there was a central-eccentric location bias in the
      pointing task, and either a bias restricted to the smaller numbers (left side) or
      no significant number bias (right side). Prior number location also biased
      subsequent number judgments towards the opposite side. Findings support a lexical
      influence on auditory spatial perception, with a linear mapping near midline and
      more complex relations at lateral locations. Results may reflect coding of
      dedicated spatial channels, with two representing lateral positions in each
      hemispace, and the midline area represented by either their overlap or a separate
      third channel.

PMID- 29222525
TI  - Conserved Gene Microsynteny Unveils Functional Interaction Between Protein
      Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families.
AB  - Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein
      folding and cell-surface thiol-redox control of thrombosis and vascular
      remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and
      cytoskeleton organization, however the related underlying mechanisms are unclear.
      Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2
      are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI),
      known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these
      three microsyntenic regions reveal their emergence by two successive duplication
      events of a primordial gene pair in the last common vertebrate ancestor. The
      arrangement, however, is substantially older, detectable in echinoderms,
      nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription
      orientation emerged early in animal evolution and has been largely maintained.
      PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common
      cis-regulatory elements. Analysis of gene expression datasets supports evidence
      for PDI/RhoGDI coexpression in developmental/inflammatory contexts.
      PDIA1/RhoGDIalpha were co-induced in endothelial cells upon CRISP-R-promoted
      transcription activation of each pair component, and also in mouse arterial
      intima during flow-induced remodeling. We provide evidence for physical
      interaction between both proteins. These data support strong functional links
      between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny
      along > 800-million years of evolution.

PMID- 29222527
TI  - The chemokines CXCL12 and CXCL14 differentially regulate connective tissue
      markers during limb development.
AB  - Connective tissues (CT) support and connect organs together. Understanding the
      formation of CT is important, as CT deregulation leads to fibrosis. The
      identification of CT specific markers has contributed to a better understanding
      of CT function during development. In developing limbs, Osr1 transcription factor
      is involved in the differentiation of irregular CT while the transcription factor
      Scx labels tendon. In this study, we show that the CXCL12 and CXCL14 chemokines
      display distinct expression pattern in limb CT during chick development. CXCL12
      positively regulates the expression of OSR1 and COL3A1, a collagen subtype of
      irregular CT, while CXCL14 activates the expression of the tendon marker SCX. We
      provide evidence that the CXCL12 effect on irregular CT involves CXCR4 receptor
      and vessels. In addition, the expression of CXCL12, CXCL14 and OSR genes is
      suppressed by the anti-fibrotic BMP signal. Finally, mechanical forces, known to
      be involved in adult fibrosis, control the expression of chemokines, CT
      associated transcription factors and collagens during limb development. Such
      unexpected roles of CXCL12 and CXCL14 chemokines during CT differentiation can
      contribute to a better understanding of the fibrosis mechanisms in adult
      pathological conditions.

PMID- 29222528
TI  - Structure and Dynamics of Cas9 HNH Domain Catalytic State.
AB  - The bacterial CRISPR-Cas9 immune system has been harnessed as a powerful and
      versatile genome-editing tool and holds immense promise for future therapeutic
      applications. Despite recent advances in understanding Cas9 structures and its
      functional mechanism, little is known about the catalytic state of the Cas9 HNH
      nuclease domain, and identifying how the divalent metal ions affect the HNH
      domain conformational transition remains elusive. A deeper understanding of Cas9
      activation and its cleavage mechanism can enable further optimization of Cas9
      based genome-editing specificity and efficiency. Using two distinct molecular
      dynamics simulation techniques, we have obtained a cross-validated catalytically
      active state of Cas9 HNH domain primed for cutting the target DNA strand.
      Moreover, herein we demonstrate the essential roles of the catalytic Mg2+ for the
      active state formation and stability. Importantly, we suggest that the derived
      catalytic conformation of the HNH domain can be exploited for rational
      engineering of Cas9 variants with enhanced specificity.

PMID- 29222530
TI  - Seizure Rates in Enzalutamide-Treated Men With Metastatic Castration-Resistant
      Prostate Cancer and Risk of Seizure: The UPWARD Study.
AB  - Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men
      with metastatic castration-resistant prostate cancer (mCRPC). In controlled
      clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients
      with a history of or risk factors for seizure were excluded. Men with mCRPC and
      seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years
      without enzalutamide exposure. Objective: To assess seizure incidence in patients
      with seizure risk factors who were receiving enzalutamide for mCRPC. Design,
      Setting, and Participants: The UPWARD study (A Study to Evaluate the Potential
      Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer
      Patients Treated With Enzalutamide) is an international, multicenter (73 sites in
      20 countries), single-arm, open-label safety study in institutional practice.
      Data were collected from September 25, 2013, to February 1, 2016. Patients had at
      least 1 risk factor for seizure at baseline, including medications that lower
      seizure threshold, history of stroke, or history of seizure. Exclusion criteria
      included seizure (assessed by neurologic examination and history) requiring
      antiseizure medication within the past 12 months. Intervention: Treatment with
      oral enzalutamide, 160 mg/d. Main Outcomes and Measures: The primary end point
      was the proportion of evaluable patients with 1 or more independently confirmed
      seizures during the 4-month study period; evaluable patients were defined as
      those who had 3 months or more of treatment or 1 or more confirmed seizures
      during this treatment period. Results: Of 423 patients with mCRPC receiving
      enzalutamide, 366 were evaluated. At baseline, risk factors for seizure included
      medications that lowered seizure threshold (242 of 423 patients [57.2%]), history
      of brain injury (112 [26.5%]), and history of cerebrovascular accident or
      transient ischemic attack (94 [22.2%]). Four of the 366 evaluable patients (1.1%)
      had at least 1 confirmed seizure within 4 months of enzalutamide initiation, and
      3 (0.8%) additional patients experienced a seizure within 4 months following the
      4-month study period. The incidence of confirmed seizure was 2.6 per 100 patient
      years (7 seizures). Of the 423 patients receiving enzalutamide, 357 (84.4%)
      experienced at least 1 treatment-emergent adverse event (an adverse event
      temporally related to the study treatment); 141 (33.3%) had at least 1 serious
      treatment-emergent adverse event, and 29 (6.9%) had at least 1 drug-related
      serious adverse event. Thirty-eight deaths (9.0%) were reported during treatment
      or within 30 days of drug discontinuation; 4 were considered possibly drug
      related. Conclusions and Relevance: Incidence of seizure is similar in patients
      with mCRPC and similar seizure risk factors with or without enzalutamide
      exposure. The risk profile presented, along with the previously established
      efficacy of enzalutamide, suggests that enzalutamide can benefit patients with a
      history of seizures or other predisposing factors, but each patient should be
      closely monitored for the duration of treatment.

PMID- 29222531
TI  - Effects of Aging on Interference During Pronoun Resolution.
AB  - Purpose: The purpose of this study is to investigate the effects of healthy aging
      on the ability to suppress grammatically illicit antecedents during pronoun
      resolution. Method: In 2 reading-based acceptability-judgment experiments,
      younger and older speakers of German read sentences containing an object pronoun
      and 2 potential antecedent noun phrases, only 1 of which was a grammatically
      licit antecedent. Using a gender-mismatch paradigm, we compared to what extent
      younger and older speakers were sensitive to feature (mis)matches between the
      pronoun and either of the 2 antecedents. All participants were fluent readers of
      German and had finished at least secondary education. Results: Experiment 1 used
      a self-paced reading paradigm. Older speakers showed greater sensitivity than
      younger ones to mismatching licit antecedents, but no group showed any evidence
      of interference from an intervening competitor antecedent. In Experiment 2, we
      increased the processing demand by using paced word-by-word stimulus presentation
      and longer sentences. Here, older participants showed reduced sensitivity, in
      comparison with younger people, to mismatching licit antecedents. Unlike our
      younger participants, they showed signs of distraction by the presence of a
      linearly closer but grammatically inappropriate antecedent when no appropriate
      antecedent was available. Conclusion: Together, our results show that older (but
      not younger) speakers' ability to compute intrasentential referential
      dependencies is vulnerable to increased task demands. We briefly discuss a
      potential role for executive functions, such as interference control.

PMID- 29222529
TI  - Prediction of cassava protein interactome based on interolog method.
AB  - Cassava is a starchy root crop whose role in food security becomes more
      significant nowadays. Together with the industrial uses for versatile purposes,
      demand for cassava starch is continuously growing. However, in-depth study to
      uncover the mystery of cellular regulation, especially the interaction between
      proteins, is lacking. To reduce the knowledge gap in protein-protein interaction
      (PPI), genome-scale PPI network of cassava was constructed using interolog-based
      method (MePPI-In, available at http://bml.sbi.kmutt.ac.th/ppi ). The network was
      constructed from the information of seven template plants. The MePPI-In included
      90,173 interactions from 7,209 proteins. At least, 39 percent of the total
      predictions were found with supports from gene/protein expression data, while
      further co-expression analysis yielded 16 highly promising PPIs. In addition,
      domain-domain interaction information was employed to increase reliability of the
      network and guide the search for more groups of promising PPIs. Moreover, the
      topology and functional content of MePPI-In was similar to the networks of
      Arabidopsis and rice. The potential contribution of MePPI-In for various
      applications, such as protein-complex formation and prediction of protein
      function, was discussed and exemplified. The insights provided by our MePPI-In
      would hopefully enable us to pursue precise trait improvement in cassava.

PMID- 29222532
TI  - Acute Solar Retinopathy Imaged With Adaptive Optics, Optical Coherence Tomography
      Angiography, and En Face Optical Coherence Tomography.
AB  - Importance: Solar retinopathy is a rare form of retinal injury that occurs after
      direct sungazing. Objective: To enhance understanding of the structural changes
      that occur in solar retinopathy by obtaining high-resolution in vivo en face
      images. Design, Setting, and Participant: Case report of a young adult woman who
      presented to the New York Eye and Ear Infirmary with symptoms of acute solar
      retinopathy after viewing the solar eclipse on August 21, 2017. Main Outcomes and
      Measures: Results of comprehensive ophthalmic examination and images obtained by
      fundus photography, microperimetry, spectral-domain optical coherence tomography
      (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en
      face OCT. Results: The patient was examined after viewing the solar eclipse.
      Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant.
      Spectral-domain OCT images were consistent with mild and severe acute solar
      retinopathy in the right and left eye, respectively. Microperimetry was normal in
      the right eye but showed paracentral decreased retinal sensitivity in the left
      eye with a central absolute scotoma. Adaptive optics images of the right eye
      showed a small region of nonwaveguiding photoreceptors, while images of the left
      eye showed a large area of abnormal and nonwaveguiding photoreceptors. Optical
      coherence tomography angiography images were normal in both eyes. En face OCT
      images of the right eye showed a small circular hyperreflective area, with
      central hyporeflectivity in the outer retina of the right eye. The left eye
      showed a hyperreflective lesion that intensified in area from inner to middle
      retina and became mostly hyporeflective in the outer retina. The shape of the
      lesion on adaptive optics and en face OCT images of the left eye corresponded to
      the shape of the scotoma drawn by the patient on Amsler grid. Conclusions and
      Relevance: Acute solar retinopathy can present with foveal cone photoreceptor
      mosaic disturbances on adaptive optics scanning light ophthalmoscopy imaging.
      Corresponding reflectivity changes can be seen on en face OCT, especially in the
      middle and outer retina. Young adults may be especially vulnerable and need to be
      better informed of the risks of viewing the sun with inadequate protective
      eyewear.

PMID- 29222534
TI  - Society Awards 2017.

PMID- 29222535
TI  - A Peculiar Adenocarcinoma.

PMID- 29222536
TI  - 2017 Summer Biomechanics, Bioengineering, and Biotransport Conference Student
      Paper Competition.

PMID- 29222533
TI  - Elastic Fibers and Large Artery Mechanics in Animal Models of Development and
      Disease.
AB  - Development of a closed circulatory system requires that large arteries adapt to
      the mechanical demands of high, pulsatile pressure. Elastin and collagen uniquely
      address these design criteria in the low and high stress regimes, resulting in a
      nonlinear mechanical response. Elastin is the core component of elastic fibers,
      which provide the artery wall with energy storage and recoil. The integrity of
      the elastic fiber network is affected by component insufficiency or
      disorganization, leading to an array of vascular pathologies and compromised
      mechanical behavior. In this review, we discuss how elastic fibers are formed and
      how they adapt in development and disease. We discuss elastic fiber contributions
      to arterial mechanical behavior and remodeling. We primarily present data from
      mouse models with elastic fiber deficiencies, but suggest that alternate small
      animal models may have unique experimental advantages and the potential to
      provide new insights. Advanced ultrastructural and biomechanical data are
      constantly being used to update computational models of arterial mechanics. We
      discuss the progression from early phenomenological models to microstructurally
      motivated strain energy functions for both collagen and elastic fiber networks.
      Although many current models individually account for arterial adaptation,
      complex geometries, and fluid-solid interactions (FSIs), future models will need
      to include an even greater number of factors and interactions in the complex
      system. Among these factors, we identify the need to revisit the role of time
      dependence and axial growth and remodeling in large artery mechanics, especially
      in cardiovascular diseases that affect the mechanical integrity of the elastic
      fibers.

PMID- 29222537
TI  - The Effects of Palate Features and Glossectomy Surgery on /s/ Production.
AB  - Purpose: The aims of this article were to determine the effects of hard palate
      morphology and glossectomy surgery on tongue position and shape during /s/ for
      patients with small tumors. The first expectation was that laminal /s/ would be
      more prevalent in patients, than apical, due to reduced tongue tip control after
      surgery. The second was that patients would hold the tongue more anteriorly than
      controls to compensate for reduced tongue mass. Method: Three-dimensional tongue
      volumes were calculated from magnetic resonance imaging for the whole tongue and
      the portion anterior to the first molar during the /s/ in /esuk/ for 21 controls
      and 14 patients. These volumes were used to calculate tongue anteriority and
      cross-sectional shape. Dental casts were used to measure palate perimeter,
      height, and width of the hard palate. Results: Palate height correlated with
      tongue height in controls (p < .05), but not patients. In patients, tongue
      anteriority correlated negatively with canine width and cross-sectional tongue
      shape (p < .05). Controls with a high palate favored laminal /s/. Patients
      preferred laminal /s/ regardless of palate height (p < .01). Conclusions: For
      controls, hard palate height affected tongue height; a higher palate yielded a
      higher tongue. For patients, hard palate width affected tongue width; a narrower
      palate yielded a more anterior tongue. Tongue shape was unaffected by any palate
      features. Preference for /s/ showed an interaction effect between subject and
      palate height. Controls with high palates preferred a laminal /s/. All patients
      preferred a laminal /s/; glossectomy surgery may reduce tongue tip control.

PMID- 29222538
TI  - Collinearity and Sample Coverage Issues in the Objective Measurement of Vocal
      Quality: The Case of Roughness and Breathiness.
AB  - Purpose: The aim of the study was to address the reported inconsistencies in the
      relationship between objective acoustic measures and perceptual ratings of vocal
      quality. Method: This tutorial moves away from the more widely examined problems
      related to obtaining the perceptual ratings and the acoustic measures and centers
      in less scrutinized issues regarding the procedure to establish the
      correspondence. Expressions for the most common measure of association between
      perceptual and acoustic measures (Pearson's r) are derived using a multiple
      linear regression model. The particular case where the multiple linear regression
      involves only roughness and breathiness is discussed to illustrate the issues.
      Results: Most problems reported regarding inconsistent findings in the
      relationship between given acoustic measures and particular perceptual ratings
      could be linked to sample properties not directly related to the actual
      relationship. The influential sample properties are the collinearity between the
      regressors in the multiple linear regression and their relative variances.
      Recommendations on how to rule out this possible cause of inconsistency are
      given, varying in scope from data collection, reporting, manipulation, and
      results interpretation. Conclusions: The problems described can be extended to
      more general cases than the exemplified roughness and breathiness sample's
      coverage. Ruling out this possible cause of inconsistency would increase the
      validity of the results reported.

PMID- 29222539
TI  - Sensory Changes and the Hearing Loss-Cognition Link: The Cognitive Ear.

PMID- 29222540
TI  - Validation Study of the American Joint Committee on Cancer Eighth Edition
      Prognostic Stage Compared With the Anatomic Stage in Breast Cancer.
AB  - Importance: The American Joint Committee on Cancer (AJCC) eighth edition staging
      manual introduced a new prognostic stage for breast cancer incorporating biologic
      factors in addition to traditional anatomic factors. Objective: To perform a
      validation study of the AJCC eighth edition prognostic stage in a single
      institution cohort and a large population database. Design, Setting, and
      Participants: Patients with breast cancer treated with surgery as an initial
      intervention were identified in a prospective institutional database from The
      University of Texas MD Anderson Cancer Center and the California Cancer Registry.
      Vital status data were complete through December 31, 2016, in The University of
      Texas MD Anderson cohort and through December 31, 2014, in the California Cancer
      Registry cohort. Patients receiving neoadjuvant systemic therapy, those with
      inflammatory or rare breast cancers, and those with unknown clinicopathologic
      factors were excluded. Factors evaluated included T, N, and M categories and
      tumor grade, as well as estrogen receptor, progesterone receptor, and HER2
      status. Main Outcomes and Measures: Disease-specific survival was calculated by
      the Kaplan-Meier method. The Harrell concordance index (C index) was used to
      quantify models' predictive performance, and the Akaike information criterion
      (AIC) was used to compare model fits. Results: A total of 3327 patients with
      stage I to IIIC breast cancer treated between 2007 and 2013 at The University of
      Texas MD Anderson Cancer Center (median follow-up of 5 years) with complete
      clinicopathologic data were identified. Compared with the AJCC anatomic stage,
      the prognostic stage upstaged 29.5% of patients and downstaged 28.1%. The
      prognostic stage (C index, 0.8357 and AIC, 816.8) provided more accurate
      stratification with respect to disease-specific survival than the anatomic stage
      (C index, 0.737 and AIC, 1039.8) (P < .001 for the C index). A total of 54 727
      patients with stage I to IV breast cancer treated between 2005 and 2009 were
      identified in the California Cancer Registry (median follow-up of 7 years). The
      prognostic stage upstaged 31.0% of patients and downstaged 20.6%. The prognostic
      stage (C index, 0.8426 and AIC, 80 661.68) performed better than the anatomic
      stage (C index, 0.8097 and AIC, 81 577.89) (P < .001 for the C index).
      Conclusions and Relevance: The prognostic stage provided more accurate prognostic
      information than the anatomic stage alone in both a single-institution cohort and
      a large population database, thereby supporting its use in breast cancer staging.

PMID- 29222541
TI  - Estimating Cost-effectiveness of a Multimodal Ovarian Cancer Screening Program in
      the United States: Secondary Analysis of the UK Collaborative Trial of Ovarian
      Cancer Screening (UKCTOCS).
AB  - Importance: The United Kingdom Collaborative Trial of Ovarian Cancer Screening
      (UKCTOCS) is the largest randomized clinical trial to evaluate screening's impact
      on ovarian cancer mortality, assigning women to multimodal screening (MMS) with
      serum cancer antigen 125 (CA-125) interpreted using a risk algorithm. If the MMS
      screening method is eventually shown to reduce mortality and be cost-effective,
      then it may be accepted by the medical community as a feasible screening tool.
      Objective: To estimate the cost-effectiveness of an MMS screening program in the
      United States. Design, Setting, and Participants: A Markov simulation model was
      constructed using data from UKCTOCS to compare MMS with no screening in the
      United States. Screening would begin at the age of 50 years for women in the
      general population. Published estimates of the long-term effect of MMS screening
      on ovarian cancer mortality and the trial's published hazard ratios were used to
      simulate mortality estimates up to 40 years from start of screening. Base-case
      costs included CA-125, ultrasound, and false-positive work-up results, in
      addition to a risk algorithm cost estimate of $100. The utility and costs of
      ovarian cancer treatment were incorporated into the model. Interventions:
      Screening strategies varied by costs of the algorithm and treatment for advanced
      ovarian cancer, rates of screening compliance, ovarian cancer incidence, and
      extrapolation of ovarian cancer mortality. Main Outcomes and Measures: Costs,
      quality-adjusted life-years (QALYs), and mortality reduction of ovarian cancer
      screening. Results: Multimodal screening is both more expensive and more
      effective in reducing ovarian cancer mortality over a lifetime than no screening.
      After accounting for uncertainty in the underlying parameters, screening women
      starting at age 50 years with MMS is cost-effective 70% of the time, when
      decision makers are willing to pay $150 000 per QALY. Screening reduced mortality
      by 15%, with an incremental cost-effectiveness ratio (ICER) ranging from $106 187
      (95% CI, $97 496-$127 793) to $155 256 (95% CI, $150 369-$198 567). Conclusions
      and Relevance: Ovarian cancer screening is potentially cost-effective in the
      United States depending on final significance of mortality reduction and cost of
      the CA-125 risk algorithm. These results are limited by uncertainty around the
      effect of screening on ovarian cancer mortality beyond the 11 years of UKCTOCS.

PMID- 29222542
TI  - Engaging With Patients on Health Policy Changes: An Urgent Issue.

PMID- 29222543
TI  - Disclosures in Nutrition Research: Why It Is Different.

PMID- 29222544
TI  - Association of Age-Related Hearing Loss With Cognitive Function, Cognitive
      Impairment, and Dementia: A Systematic Review and Meta-analysis.
AB  - Importance: Epidemiologic research on the possible link between age-related
      hearing loss (ARHL) and cognitive decline and dementia has produced inconsistent
      results. Clarifying this association is of interest because ARHL may be a risk
      factor for outcomes of clinical dementia. Objectives: To examine and estimate the
      association between ARHL and cognitive function, cognitive impairment, and
      dementia through a systematic review and meta-analysis. Data Sources and Study
      Selection: A search of PubMed, the Cochrane Library, EMBASE, and SCOPUS from
      inception to April 15, 2016, with cross-referencing of retrieved studies and
      personal files for potentially eligible studies was performed. Keywords included
      hearing, cognition, dementia, and Alzheimer disease. Cohort and cross-sectional
      studies published in peer-reviewed literature and using objective outcome
      measures were included. Case-control studies were excluded. Data Extraction and
      Synthesis: One reviewer extracted and another verified data. Both reviewers
      independently assessed study quality. Estimates were pooled using random-effects
      meta-analysis. Subgroup and meta-regression analyses of study-level
      characteristics were performed. Main Outcomes and Measures: Hearing loss measured
      by pure-tone audiometry only and objective assessment measures of cognitive
      function, cognitive impairment, and dementia. Cognitive function outcomes were
      converted to correlation coefficients (r value); cognitive impairment and
      dementia outcomes, to odds ratios (ORs). Results: Forty studies from 12 countries
      met our inclusion criteria. Of these, 36 unique studies with an estimated 20 264
      unique participants were included in the meta-analyses. Based on the pooled
      maximally adjusted effect sizes using random-effects models, a small but
      significant association was found for ARHL within all domains of cognitive
      function. Among cross-sectional studies, a significant association was found for
      cognitive impairment (OR, 2.00; 95% CI, 1.39-2.89) and dementia (OR, 2.42; 95%
      CI, 1.24-4.72). Among prospective cohort studies, a significant association was
      found for cognitive impairment (OR, 1.22; 95% CI, 1.09-1.36) and dementia (OR,
      1.28; 95% CI, 1.02-1.59) but not for Alzheimer disease (OR, 1.69; 95% CI, 0.72
      4.00). In further analyses, study, demographic, audiometric, and analyses factors
      were associated with cognitive function. Vascular dysfunction and impaired verbal
      communication may contribute to the association between hearing loss and
      cognitive decline. Conclusions and Relevance: Age-related hearing loss is a
      possible biomarker and modifiable risk factor for cognitive decline, cognitive
      impairment, and dementia. Additional research and randomized clinical trials are
      warranted to examine implications of treatment for cognition and to explore
      possible causal mechanisms underlying this relationship.

PMID- 29222545
TI  - Coefficient of Friction Between Carboxymethylated Hyaluronic Acid-Based Polymer
      Films and the Ocular Surface.
AB  - Purpose: Hyaluronic acid-based polymer films are emerging as drug-delivery
      vehicles for local and continuous drug administration to the eye. The highly
      lubricating hyaluronic acid increases comfort, but displaces films from the eye,
      reducing drug exposure and efficacy. Previous studies have shown that careful
      control of the surface interaction of the film with the eye is critical for
      improved retention. Methods: In this study, the frictional interaction of a
      carboxymethylated, hyaluronic acid-based polymer (CMHA-S) with and without
      methylcellulose was quantified against ovine and human sclera at three axial
      loads (0.3, 0.5, and 0.7 N) and four sliding velocities (0.3, 1.0, 10, and 30
      mm/s). Results: Static coefficients of friction significantly increased with rate
      (P < 0.003), ranging between 0.18 +/- 0.08 and 0.46 +/- 0.13 for 0.3 to 30 mm/s,
      respectively. Friction became more rate-dependent when methylcellulose was added
      to CMHA-S. Kinetic coefficient of friction was not affected by rate, and averaged
      0.15 +/- 0.1. Methylcellulose increased CMHA-S static and kinetic friction by 60%
      and 80%, respectively, but was also prone to wear during testing. Conclusions:
      These data suggest that methylcellulose can be used to create a friction
      differential on the film, but a potentially increased degradation rate with the
      methylcellulose must be considered in the design.

PMID- 29222546
TI  - Intraretinal Correlates of Reticular Pseudodrusen Revealed by Autofluorescence
      and En Face OCT.

PMID- 29222547
TI  - Author Response: Intraretinal Correlates of Reticular Pseudodrusen Revealed by
      Autofluorescence and En Face OCT.

PMID- 29222548
TI  - The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in
      Geographic Atrophy.

PMID- 29222549
TI  - Author Response: The Evolution of the Plateau, an Optical Coherence Tomography
      Signature Seen in Geographic Atrophy.

PMID- 29222550
TI  - Tissue Transglutaminase Elevates Intraocular Pressure in Mice.
AB  - Purpose: Tissue transglutaminase (TGM2) is elevated in glaucomatous trabecular
      meshwork (TM) tissues. We investigated whether increased expression of TGM2
      increases extracellular matrix crosslinking in the TM, thereby increasing aqueous
      humor outflow resistance and elevating intraocular pressure (IOP) in mouse eyes.
      Methods: GTM3, primary human GTM 125-05, and cultured mouse TM cells were
      transduced with adenovirus serotype 5 expressing human transglutaminase 2
      (Ad5.TGM2; multiplicity of infection [MOI]-75) and fixed for immunocytochemistry.
      To test the effect on IOP in living eyes, Ad5.TGM2 was injected intravitreally
      into one eye of BALB/cJ (n = 18) or C57BL/6J mice (n = 9). The uninjected
      contralateral eye and Ad5.GFP served as controls. Daytime conscious IOPs were
      measured twice per week. Aqueous outflow facility (C) was measured by constant
      flow infusion on completion of IOP measurements. Immunohistochemistry was
      performed on BALB/cJ mouse eyes to study TGM2 expression and activity. Results:
      The treatment of cultured TM cells with Ad5.TGM2 increased immunostaining of N
      epsilon(gamma-glutamyl) lysine crosslinks. Ad5.TGM2 injection significantly
      increased IOP in BALB/cJ (15.86 mm Hg [injected] vs. 10.70 mm Hg [control]) and
      in C57BL/6J mice (17.09 mm Hg [injected] vs. 12.01 mm Hg [control]). Mean aqueous
      outflow facility in the injected eyes of BALB/cJ (0.013 MUL/min/mm Hg) and
      C57BL/6J mice (0.012 MUL/min/mm Hg) was significantly lower than in the
      uninjected control eyes (BALB/cJ, 0.021 MUL/min/mm Hg; C57BL/6J, 0.019 MUL/min/mm
      Hg). The Ad5.TGM2 transduction of mouse eyes increased TGM2 expression in the TM
      region and increased N-epsilon(gamma-glutamyl) lysine crosslinks. Conclusions:
      The increased expression of TGM2 in the TM increases N-epsilon(gamma-glutamyl)
      lysine crosslinking in the TM, increases aqueous outflow resistance, and elevates
      IOP in mice. TGM2 may be at least partially responsible for ocular hypertension
      in POAG.

PMID- 29222552
TI  - Animal Models of Retinal Vein Occlusion.
AB  - Purpose: To provide a comprehensive and current review on the available
      experimental animal models of retinal vein occlusion (RVO) and to identify their
      strengths and limitations with the purpose of helping researchers to plan
      preclinical studies on RVO. Methods: A systematic review of the literature on
      experimental animal models of RVO was undertaken. Medline, SCOPUS, and Web of
      Science databases were searched. Studies published between January 1, 1965, and
      March 31, 2017, and that met the inclusion criteria were reviewed. The data
      extracted included animal species used, methods of inducing RVO, and the clinical
      and histopathologic features of the models, especially in relation to strengths,
      limitations, and faithfulness to clinical sequelae. Results: A total of 128
      articles fulfilling the inclusion criteria were included. Several species were
      used to model human branch and central RVO (BRVO; CRVO) with nonhuman primates
      being the most common, followed by rodents and pigs. BRVO and CRVO were most
      commonly induced by laser photocoagulation and all models showed early features
      of clinical disease, including retinal hemorrhages and retinal edema. These
      features made many of the models adequate for studying the acute phase of BRVO
      and CRVO, although macular edema, retinal ischemia, and neovascular complications
      were observed in only a few experimental animal models (laser-induced model in
      rodents, pigs, and nonhuman primates, diathermy-induced model in pigs, and
      following intravitreal injection of PD0325901 in rabbits for BRVO; and in the
      laser-induced model in rodents, rabbits, and nonhuman primates, diathermy-induced
      model in nonhuman primates, following permanent ligation of the central retinal
      vein in nonhuman primates, and with intravitreal injection of thrombin in rabbits
      for CRVO). Conclusions: Experimental animal models of RVO are available to study
      the pathogenesis of this disease and to evaluate diagnostic/prognostic biomarkers
      and to develop new therapeutics. Data available suggest laser-induced RVO in pigs
      and rodents to be overall the best models of BRVO and the laser-induced RVO
      rodents the best model for CRVO.

PMID- 29222554
TI  - My Unfortunate Introduction Into the Financial Toxicity of Cancer Care in America
      March Forth.

PMID- 29222551
TI  - Neutrophil and T-Cell Homeostasis in the Closed Eye.
AB  - Purpose: This study sought to examine the changes and phenotype of the tear
      neutrophil and T-cell populations between early eyelid closure and after a full
      night of sleep. Methods: Fourteen healthy participants were recruited and trained
      to wash the ocular surface with PBS for at-home self-collection of ocular surface
      and tear leukocytes following up to 1 hour of sleep and a full night of sleep
      (average 7 hours), on separate days. Cells were isolated, counted, and incubated
      with fluorescently labeled antibodies to identify neutrophils, monocytes, and T
      cells. For neutrophil analysis, samples were stimulated with lipopolysaccharide
      (LPS) or calcium ionophore (CaI) before antibody incubation. Flow cytometry was
      performed. Results: Following up to 1 hour of sleep, numerous leukocytes were
      collected (2.6 * 105 +/- 3.0 * 105 cells), although significantly (P < 0.005)
      more accumulated with 7 hours of sleep (9.9 * 105 +/- 1.2* 106 cells).
      Neutrophils (65%), T cells (3%), and monocytes (1%) were identified as part of
      the closed eye leukocyte infiltration following 7 hours of sleep. Th17 cells
      represented 22% of the total CD4+ population at the 7-hour time point. Neutrophil
      phenotype changed with increasing sleep, with a downregulation of membrane
      receptors CD16, CD11b, CD14, and CD15, indicating a loss in the phagocytic
      capability of neutrophils. Conclusions: Neutrophils begin accumulating in the
      closed eye conjunctival sac much earlier than previously demonstrated. The closed
      eye tears are also populated with T cells, including a subset of Th17 cells. The
      closed eye environment is more inflammatory than previously thought and is
      relevant to understanding ocular homeostasis.

PMID- 29222553
TI  - Ghrelin Attenuates Retinal Neuronal Autophagy and Apoptosis in an Experimental
      Rat Glaucoma Model.
AB  - Purpose: Ghrelin, a natural ligand for the growth hormone secretagogue receptor
      type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We
      therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated
      neuroprotection with a rat chronic intraocular hypertension (COH) model. Methods:
      The rat COH model was produced by blocking episcleral veins. A combination of
      immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of
      retinal ganglion cells (RGCs) was used. Results: Elevation of intraocular
      pressure induced a significant increase in ghrelin and GHSR-1a expression in
      retinal cells, including RGCs and Muller cells. Western blot confirmed that the
      protein levels of ghrelin exhibited a transient upregulation at week 2 after
      surgery (G2w), while the GHSR-1a protein levels were maintained at high levels
      from G2w to G4w. In COH retinas, the ratio of LC3-II/LC-I and beclin1, two
      autophagy-related proteins, were increased from G1w to G4w, and the cleavage
      product of caspase3, an apoptotic executioner, was detected from G2w to G4w.
      Intraperitoneal injection of ghrelin significantly increased the number of
      surviving RGCs; inhibited the changes of LC3-II/LC-I, beclin1, and the cleavage
      products of caspase3; and reduced the number of TUNEL-positive cells in COH
      retinas. Ghrelin treatment also reversed the decreased levels of p-Akt and p
      mTOR, upregulated GHSR-1a protein levels, and attenuated glial fibrillary acidic
      protein levels in COH retinas. Conclusions: All these results suggest that
      ghrelin may provide neuroprotective effect in COH retinas through activating
      ghrelin/GHSR-1a system, which was mediated by inhibiting retinal autophagy,
      ganglion cell apoptosis, and Muller cell gliosis.

PMID- 29222556
TI  - 2017 Richard Skalak Award.

PMID- 29222555
TI  - Audiological Assessment of Word Recognition Skills in Persons With Aphasia.
AB  - Purpose: The purpose of this study was to evaluate the ability of persons with
      aphasia, with and without hearing loss, to complete a commonly used open-set word
      recognition test that requires a verbal response. Furthermore, phonotactic
      probabilities and neighborhood densities of word recognition errors were assessed
      to explore potential underlying linguistic complexities that might differentially
      influence performance among groups. Method: Four groups of adult participants
      were tested: participants with no brain injury with normal hearing, participants
      with no brain injury with hearing loss, participants with brain injury with
      aphasia and normal hearing, and participants with brain injury with aphasia and
      hearing loss. The Northwestern University Auditory Test No. 6 (NU-6; Tillman &
      Carhart, 1966) was administered. Those participants who were unable to respond
      orally (repeating words as heard) were assessed with the Picture Identification
      Task (Wilson & Antablin, 1980), permitting a picture-pointing response instead.
      Error patterns from the NU-6 were assessed to determine whether phonotactic
      probability influenced performance. Results: All participants with no brain
      injury and 72.7% of the participants with aphasia (24 out of 33) completed the NU
      6. Furthermore, all participants who were unable to complete the NU-6 were able
      to complete the Picture Identification Task. There were significant group
      differences on NU-6 performance. The 2 groups with normal hearing had
      significantly higher scores than the 2 groups with hearing loss, but the 2 groups
      with normal hearing and the 2 groups with hearing loss did not differ from one
      another, implying that their performance was largely determined by hearing loss
      rather than by brain injury or aphasia. The neighborhood density, but not
      phonotactic probabilities, of the participants' errors differed across groups
      with and without aphasia. Conclusions: Because the vast majority of the
      participants with aphasia examined could be tested readily using an instrument
      such as the NU-6, clinicians should not be reticent to use this test if patients
      are able to repeat single words, but routine use of alternative tests is
      encouraged for populations of people with brain injuries.

PMID- 29222557
TI  - Accentuate the Negative: Grammatical Errors During Narrative Production as a
      Clinical Marker of Central Nervous System Abnormality in School-Aged Children
      With Fetal Alcohol Spectrum Disorders.
AB  - Purpose: The purpose of this study was to examine (a) whether increased
      grammatical error rates during a standardized narrative task are a more
      clinically useful marker of central nervous system abnormality in Fetal Alcohol
      Spectrum Disorders (FASD) than common measures of productivity or grammatical
      complexity and (b) whether combining the rate of grammatical errors with the rate
      of cohesive referencing errors can improve utility of a standardized narrative
      assessment task for FASD diagnosis. Method: The method used was retrospective
      analysis of narrative and clinical data from 138 children (aged 7-12 years; 69
      with FASD, 69 typically developing). Narrative analysis was conducted blind to
      diagnosis. Measures of grammatical error, productivity and complexity, and
      cohesion were used independently and in combination to predict whether a story
      was told by a child with an FASD diagnosis. Results: Elevated grammatical error
      rates were more common in children with FASD, and this difference facilitated a
      more accurate prediction of FASD status than measures of productivity and
      grammatical complexity and, when combined with an accounting of cohesive
      referencing errors, significantly improved sensitivity to FASD over standard
      practice. Conclusion: Grammatical error rates during a narrative are a viable
      behavioral marker of the kinds of central nervous system abnormality associated
      with prenatal alcohol exposure, having significant potential to contribute to the
      FASD diagnostic process.

PMID- 29222558
TI  - A Policy That Encourages Wastage of Expensive Medications-The JW Modifier.

PMID- 29222559
TI  - The Listening and Spoken Language Data Repository: Design and Project Overview.
AB  - Purpose: The purpose of the Listening and Spoken Language Data Repository (LSL
      DR) was to address a critical need for a systemwide outcome data-monitoring
      program for the development of listening and spoken language skills in highly
      specialized educational programs for children with hearing loss highlighted in
      Goal 3b of the 2007 Joint Committee on Infant Hearing position statement
      supplement. Method: The LSL-DR is a multicenter, international data repository
      for recording and tracking the demographics and longitudinal outcomes achieved by
      children who have hearing loss who are enrolled in private, specialized programs
      focused on supporting listening and spoken language development. Since 2010,
      annual speech-language-hearing outcomes have been prospectively obtained by
      qualified clinicians and teachers across 48 programs in 4 countries. Results: The
      LSL-DR has been successfully implemented, bringing together the data collection
      efforts of these programs to create a large and diverse data repository of 5,748
      children with hearing loss. Conclusion: Due to the size and diversity of the
      population, the range of assessments entered, and the demographic information
      collected, the LSL-DR will provide an unparalleled opportunity to examine the
      factors that influence the development of listening in spoken language in this
      population.

PMID- 29222560
TI  - Masseteric Nerve Transfer for Facial Nerve Paralysis: A Systematic Review and
      Meta-analysis.
AB  - Importance: A review of the role of masseteric nerve transfer is needed to guide
      its use in facial reanimation. Objective: To systematically review the available
      literature, and, when applicable, analyze the combined outcomes of masseteric
      nerve transfer to better define its role in reanimation and to guide further
      research. Data Sources: Two independent researchers conducted the review using
      PubMed-NCBI and Scopus literature databases for studies on masseteric nerve
      transfer for facial nerve paralysis. Study Selection: Studies that examined
      masseter nerve transfer with additional cranial nerve transposition/coaptation or
      muscle flap were excluded. Data Extraction and Synthesis: Literature review and
      data extraction followed established PRISMA guidelines. Two researchers extracted
      data independently. Main Outcomes and Measures: The main planned outcomes for the
      study were quantitative results of facial nerve movement after nerve transfer
      including oral commissure movement and time to nerve recovery. Results: A total
      of 13 articles met inclusion criteria with a total of 183 patients undergoing
      masseteric nerve transfer. From those studies, there were a total of 183 patients
      who underwent masseteric nerve transfer. There were 85 men and 98 women with a
      mean (SD) age of 43 (12.2) years and mean (SD) follow up examination after
      surgery of 22 (7.6) months. Mean (SD) duration of nerve paralysis was 14 (6)
      months. Most common cause of paralysis was cerebellopontine angle tumors (81%).
      Six studies coapted the masseteric nerve to the main facial nerve trunk, whereas
      7 used distal branches (buccal or zygomatic). Four studies used interposition
      nerve grafts with great auricular nerve. Two measures, improvement in oral
      commissure excursion and length from reanimation to facial movement, were
      measured consistently across the studies. Pooled analysis showed time from
      surgery to first facial movement, described in 10 studies, to be 4.95 months (95%
      CI, 3.66 to 6.24). Distal branch coaptation improved time to recovery vs main
      branch coaptation, 3.76 vs 5.76 months (95% CI, -0.33 to 4.32), but mean
      difference was not significant. The use of interposition graft significantly
      delayed time of nerve recovery, 6.24 vs 4.06 months (95% CI, 0.20 to 4.16). When
      controlled for main trunk coaptation only, interposition nerve graft delayed
      recovery but difference was no longer statistically significant, 6.24 vs 4.75
      months (95% CI, -0.94 to 3.92). Reported complications were minor and rare
      occurring in only 6.5% (12 of 183) of patients. Conclusions and Relevance: The
      masseteric nerve was found to be a good option for nerve transfer in this patient
      population, and showed favorable results in both time to nerve recovery and
      improvement in oral commissure excursion. Level of Evidence: NA.

PMID- 29222562
TI  - Dysphagia and Pharyngeal Obstruction in a Nonsmoker.

PMID- 29222563
TI  - Quantitative Analysis and Classification of the Nasal Base Using a Parametric
      Model.
AB  - Importance: The nasal base view is often overlooked in rhinoplasty analysis and,
      unlike lateral and frontal views, lacks detailed quantitative analysis and
      descriptors. While shape-category analysis of the nasal base is well established,
      these descriptive methods remain subjective and do not facilitate quantitative
      analysis. Objective: To establish a simple and quantitative classification scheme
      using a multiple-parameter numerical model for analyzing and describing the shape
      of the nasal base. Design, Setting, and Participants: Deidentified photographs of
      the nasal base view were analyzed without knowledge of patients' pathology or
      medical history. Each nose was classified into 1 of 6 categories derived from
      literature (equilateral, narrow, flat, cloverleaf, boxy, and round). Finite
      parametric modeling was performed on each nose, and the correlations between the
      resulting parameters and the 6 categories were analyzed. Photographs for this
      study were acquired from the practice of a single facial plastic surgeon
      (B.J.F.W.) at a tertiary care academic medical center. One hundred twenty-one
      consecutive patients who had nasal base view photographs taken were included in
      the study. Main Outcomes and Measures: All of the 121 images were classified into
      1 of the 6 categories by 1 reviewer (C.H.B.). The contour of each nasal base was
      curve fit to a 5-parameter numerical model. The 5 parameters controlled base
      size, deviation from the midline, projection-to-width ratio, degree of nasal alar
      recurvature, and anterior-posterior positioning of nasal base bulk. A numerical
      value for each nasal base shape type was predicted by the parametric model.
      Results: In 121 patient photographs, the parametric model generated shapes that
      accurately matched the tracing of the actual nasal base contours with an average
      correlation coefficient of greater than 0.98. This finding indicates close
      approximation of the nasal base shape with the curve fit constructed by the PM.
      Parameters b (projection-to-width ratio) and e (roundedness) were shown to have
      significant differences among the groups (F statistic, 8.88; P < .001 and F
      statistic, 13.05; P < .001, respectively). These two curve-fit parameters alone
      could be used to classify nasal shape into 1 of the 6 clinically determined base
      geometries. Conclusions and Relevance: A numerical approach to classify nasal
      base shape was developed using a 5-parameter model and tested against subjective
      analysis. This model may aid in the advancement of algorithm-driven objective
      nasal analysis techniques, preoperative modeling, intraoperative guidance, and
      surgical outcome measures beyond using Likert scales. Level of Evidence: NA.

PMID- 29222564
TI  - Primary Blast Brain Injury Mechanisms: Current Knowledge, Limitations, and Future
      Directions.
AB  - Mild blast traumatic brain injury (bTBI) accounts for the majority of brain
      injury in United States service members and other military personnel worldwide.
      The mechanisms of primary blast brain injury continue to be disputed with little
      evidence to support one or a combination of theories. The main hypotheses
      addressed in this review are blast wave transmission through the skull orifices,
      direct cranial transmission, skull flexure dynamics, thoracic surge,
      acceleration, and cavitation. Each possible mechanism is discussed using
      available literature with the goal of focusing research efforts to address the
      limitations and challenges that exist in blast injury research. Multiple
      mechanisms may contribute to the pathology of bTBI and could be dependent on
      magnitudes and orientation to blast exposure. Further focused biomechanical
      investigation with cadaver, in vivo, and finite element models would advance our
      knowledge of bTBI mechanisms. In addition, this understanding could guide future
      research and contribute to the greater goal of developing relevant injury
      criteria and mandates to protect our soldiers on the battlefield.

PMID- 29222565
TI  - Biomechanics and Mechanobiology of Saphenous Vein Grafts.
AB  - Within several weeks of use as coronary artery bypass grafts (CABG), saphenous
      veins (SV) exhibit significant intimal hyperplasia (IH). IH predisposes vessels
      to thrombosis and atherosclerosis, the two major modes of vein graft failure. The
      fact that SV do not develop significant IH in their native venous environment
      coupled with the rapidity with which they develop IH following grafting into the
      arterial circulation suggests that factors associated with the isolation and
      preparation of SV and/or differences between the venous and arterial environments
      contribute to disease progression. There is strong evidence suggesting that
      mechanical trauma associated with traditional techniques of SV preparation can
      significantly damage the vessel and might potentially reduce graft patency though
      modern surgical techniques reduces these injuries. In contrast, it seems possible
      that modern surgical technique, specifically endoscopic vein harvest, might
      introduce other mechanical trauma that could subtly injure the vein and perhaps
      contribute to the reduced patency observed in veins harvested using endoscopic
      techniques. Aspects of the arterial mechanical environment influence remodeling
      of SV grafted into the arterial circulation. Increased pressure likely leads to
      thickening of the medial wall but its role in IH is less clear. Changes in fluid
      flow, including increased average wall shear stress, may reduce IH while
      disturbed flow likely increase IH. Nonmechanical stimuli, such as exposure to
      arterial levels of oxygen, may also have a significant but not widely recognized
      role in IH. Several potentially promising approaches to alter the mechanical
      environment to improve graft patency are including extravascular supports or
      altered graft geometries are covered.

PMID- 29222566
TI  - Motivation to Address Self-Reported Hearing Problems in Adults With Normal
      Hearing Thresholds.
AB  - Purpose: The purpose of this study was to compare the motivation to change in
      relation to hearing problems in adults with normal hearing thresholds but who
      report hearing problems and that of adults with a mild-to-moderate sensorineural
      hearing loss. Factors related to their motivation were also assessed. Method: The
      motivation to change in relation to self-reported hearing problems was measured
      using the University of Rhode Island Change Assessment (McConnaughy, Prochaska, &
      Velicer, 1983). The relationship between objective and subjective measures and an
      adult's motivation was examined. Results: The level of hearing handicap did not
      differ significantly between adults with normal hearing who reported problems
      hearing in background noise and adults who had a mild-to-moderate sensorineural
      hearing loss. Hearing handicap, personal distress, and minimization of hearing
      loss were factors significantly related to motivation. Age, degree of hearing
      loss, speech-in-noise scores, working memory, and extended high-frequency average
      thresholds were not significantly related to their motivation. Conclusions:
      Adults with normal hearing thresholds but self-reported hearing problems had the
      same level of hearing handicap and were equally motivated to take action for
      their hearing problems as age-matched adults with a mild-to-moderate
      sensorineural hearing loss. Hearing handicap, personal distress, and minimization
      of hearing loss were most strongly correlated with an individual's motivation to
      change.

PMID- 29222568
TI  - Model-Driven Treatment of Childhood Apraxia of Speech: Positive Effects of the
      Speech Motor Learning Approach.
AB  - Purpose: The aim of the study was to propose the speech motor learning approach
      (Van der Merwe, 2011) as a treatment for childhood apraxia of speech and to
      determine if it will effect positive change in the ability of a 33-month-old
      child to produce untreated nonwords and words containing treated age-appropriate
      consonants (Set 1 sounds), untreated age-appropriate consonants (Set 2), and
      untreated age-inappropriate consonants (Set 3) and also to determine the nature
      and number of segmental speech errors before and after treatment. Method: An A-B
      design with multiple target measures and follow-up was implemented to assess the
      effects of treatment of Set 1. Effect sizes for whole-word accuracy were
      determined, and two criterion lines were generated following the conservative
      dual criterion method. Speech errors were judged perceptually. Results:
      Conservative dual criterion analyses indicated no reliable treatment effect due
      to rising baseline scores. Effect sizes showed significant improvement in whole
      word accuracy of untreated nonwords and real words containing age-appropriate
      treated sounds and real words containing age-appropriate untreated sounds. The
      number of errors for all three sound sets declined. Sound distortion was the most
      frequent error type. Conclusions: Preliminary evidence suggests potentially
      positive treatment effects. However, rising baseline scores limit causal
      inference. Replication with more children of different ages is necessary.
      Supplemental Materials: https://doi.org/10.23641/asha.5596708.

PMID- 29222567
TI  - Identifying Children at Risk for Language Impairment or Dyslexia With Group
      Administered Measures.
AB  - Purpose: The study aims to determine whether brief, group-administered screening
      measures can reliably identify second-grade children at risk for language
      impairment (LI) or dyslexia and to examine the degree to which parents of
      affected children were aware of their children's difficulties. Method:
      Participants (N = 381) completed screening tasks and assessments of word reading,
      oral language, and nonverbal intelligence. Their parents completed questionnaires
      that inquired about reading and language development. Results: Despite
      considerable overlap in the children meeting criteria for LI and dyslexia, many
      children exhibited problems in only one domain. The combined screening tasks
      reliably identified children at risk for either LI or dyslexia (area under the
      curve = 0.842), but they were more accurate at identifying risk for dyslexia than
      LI. Parents of children with LI and/or dyslexia were frequently unaware of their
      children's difficulties. Parents of children with LI but good word reading skills
      were the least likely of all impairment groups to report concerns or prior
      receipt of speech, language, or reading services. Conclusions: Group-administered
      screens can identify children at risk of LI and/or dyslexia with good
      classification accuracy and in less time than individually administered measures.
      More research is needed to improve the identification of children with LI who
      display good word reading skills.

PMID- 29222569
TI  - Acute Monocular Vision Loss in a Young Adult.

PMID- 29222570
TI  - Narrative Language Sampling in Typical Development: Implications for Clinical
      Trials.
AB  - Purpose: This study examined cross-sectional age-related trajectories of
      expressive language variables (syntactic complexity, lexical diversity,
      unintelligibility, dysfluency, and talkativeness) derived from a narrative
      language sampling procedure. Method: Narrative samples were analyzed from 103
      typically developing individuals, ages 4-21 years. Results: Results showed that
      this procedure was effective for the entire age range, with participants
      producing an utterance on virtually every page of the wordless picture books used
      to prompt the narrative. Importantly, the cross-sectional trajectories for
      syntactic complexity and lexical diversity showed age-related increases through
      the age of 18 years, although measures of other dimensions of language showed
      different relationships with age. Conclusions: These data inform developmental
      work and document the extent to which the narrative procedure can be used to
      characterize expressive language over a wide age range. This procedure has been
      proposed as an outcome measure for clinical trials and interventions involving
      individuals with intellectual and developmental disabilities. The present data
      document the developmental levels for which the procedure and metrics derived are
      appropriate.

PMID- 29222571
TI  - The Potential of Past Tense Marking in Oral Reading as a Clinical Marker of
      Specific Language Impairment in School-Age Children.
AB  - Purpose: The purpose of this study was twofold. The first aim was to explore
      differences in profiles of past tense marking in oral reading of school-age
      children with specific language impairment (SLI). The second aim was to explore
      the potential of past tense marking in oral reading as a clinical marker of SLI
      in school-age children. Method: This study examined oral readings of connected
      text to describe the frequency and type of reading errors on regular and
      irregular past tense verbs for 21 children with SLI as compared to 30 children
      with typical language in Grades 2 and 3. Each past tense verb token was
      categorized into 1 of 6 mutually exclusive response types: (a) correctly marked
      past tense, (b) overmarked past tense, (c) bare stem, (d) other verb inflection,
      (e) nonverb, or (f) no response. Performance across groups was compared.
      Additionally, classification statistics were calculated at several cutoffs for
      regular past tense accuracy and regular past tense finiteness marking. Results:
      For regular past tense, there was a significant group difference on accuracy.
      Children with SLI were less accurate at marking past tense when in oral reading
      than typical language peers; other response types did not differ. For irregular
      past tense, there were no group differences. In addition, there was a significant
      group difference on finiteness marking; this difference was driven by regular but
      not irregular verbs. A cutoff of 90% for regular past tense accuracy yielded
      moderate sensitivity and specificity; no cutoff for regular past tense finiteness
      marking yielded sensitivity above 70%. Conclusions: Regular past tense accuracy
      in oral reading provides promise as a clinical marker for diagnosing SLI in
      school-age children.

PMID- 29222572
TI  - Word Processing in Children With Autism Spectrum Disorders: Evidence From Event
      Related Potentials.
AB  - Purpose: This investigation was conducted to determine whether young children
      with autism spectrum disorders exhibited a canonical neural response to word
      stimuli and whether putative event-related potential (ERP) measures of word
      processing were correlated with a concurrent measure of receptive language.
      Additional exploratory analyses were used to examine whether the magnitude of the
      association between ERP measures of word processing and receptive language varied
      as a function of the number of word stimuli the participants reportedly
      understood. Method: Auditory ERPs were recorded in response to spoken words and
      nonwords presented with equal probability in 34 children aged 2-5 years with a
      diagnosis of autism spectrum disorder who were in the early stages of language
      acquisition. Average amplitudes and amplitude differences between word and
      nonword stimuli within 200-500 ms were examined at left temporal (T3) and
      parietal (P3) electrode clusters. Receptive vocabulary size and the number of
      experimental stimuli understood were concurrently measured using the MacArthur
      Bates Communicative Development Inventories. Results: Across the entire
      participant group, word-nonword amplitude differences were diminished. The
      average word-nonword amplitude difference at T3 was related to receptive
      vocabulary only if 5 or more word stimuli were understood. Conclusions: If ERPs
      are to ever have clinical utility, their construct validity must be established
      by investigations that confirm their associations with predictably related
      constructs. These results contribute to accruing evidence, suggesting that a
      valid measure of auditory word processing can be derived from the left temporal
      response to words and nonwords. In addition, this measure can be useful even for
      participants who do not reportedly understand all of the words presented as
      experimental stimuli, though it will be important for researchers to track
      familiarity with word stimuli in future investigations. Supplemental Material:
      https://doi.org/10.23641/asha.5614840.

PMID- 29222573
TI  - Incidence and Causes of Overdiagnosis of Optic Neuritis.
AB  - Importance: Diagnostic error is an important source of medical error.
      Overdiagnosis of optic neuritis may prompt unnecessary and costly diagnostic
      tests, procedures, and treatments. Objective: To assess the incidence of and
      characterize factors contributing to overdiagnosis of acute optic neuritis.
      Design, Setting, and Participants: In this retrospective clinic-based cross
      sectional study of new patient encounters, 122 patients referred for acute optic
      neuritis at a university-based Midwestern neuro-ophthalmology clinic between
      January 2014 and October 2016 were studied. Data were analyzed from September
      2016 to July 2017. Interventions: Definite diagnosis was determined by neuro
      ophthalmologists. For patients with alterative diagnoses, the Diagnosis Error
      Evaluation and Research taxonomy tool was applied to categorize the type of
      diagnostic error. Main Outcomes and Measures: The primary outcome was the primary
      type of diagnostic error in patients erroneously diagnosed as having optic
      neuritis. Secondary outcomes included final diagnosis and interventions undergone
      prior to referral. Results: A total of 122 patients were referred with acute
      optic neuritis during the study period; 88 (72.1%) were female, and the mean (SD)
      age was 42.6 (14.0) years. Of these, 49 patients (40.2%; 95% CI, 31.4-49.4) were
      confirmed to have optic neuritis, and 73 (59.8%; 95% CI, 50.6-68.6) had an
      alternative diagnosis. The most common alternative diagnoses were headache and
      eye pain, functional visual loss, and other optic neuropathies, particularly
      nonarteritic anterior ischemic optic neuropathy. The most common diagnostic error
      was eliciting or interpreting critical elements of history, which occurred in 24
      of 73 patients (33%) with alternative diagnoses. Other common errors included
      errors weighing or considering alternative diagnoses (23 patients [32%]), errors
      weighing or interpreting physical examination findings (15 patients [21%]), and
      misinterpreting diagnostic test results (11 patients [15%]). In patients with
      alterative diagnoses, 12 (16%) had normal magnetic resonance imaging findings
      preceding the referral, 12 (16%) had received a lumbar puncture, and 8 (11%) had
      received unnecessary treatment with intravenous steroids. Conclusions and
      Relevance: These data suggest that nearly 60% (95% CI, 50.6-68.6) of patients
      referred for optic neuritis have an alternative diagnosis, with the most common
      errors being overreliance on a single item of history and failure to consider
      alternative diagnoses. Understanding pitfalls leading to overdiagnosis of optic
      neuritis may improve clinicians' diagnostic process.

PMID- 29222574
TI  - Improving Hearing Aid Self-Efficacy and Utility Through Revising a Hearing Aid
      User Guide: A Pilot Study.
AB  - Purpose: This pilot study aimed to investigate whether revising a hearing aid
      user guide (HAUG) is associated with improved hearing aid self-efficacy and
      utility performance. Method: In Part 1, an HAUG was evaluated using the
      Suitability Assessment of Material (SAM) and readability formulas (Flesch Reading
      Ease [Flesch, 1943], Flesch-Kincaid Readability Formula [Kincaid, Fishburne,
      Rogers, & Chissom, 1957], and Simple Measure of Gobbledygook [McLaughlin, 1969]).
      The HAUG was revised using results from the SAM and best practice guidelines. The
      revision included generating a video. In Part 2, 30 adults with hearing
      impairment were randomly assigned to use either the original guide (N = 15) or
      the revised guide and video (N = 15) to perform a utility task. Participants'
      self-efficacy was measured using the Basic and Advanced Handling subscales of the
      Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids
      questionnaire. SAM and readability were compared between the original and revised
      guides (Doak, Doak, & Root, 1996). Results: SAM and readability were improved
      following the revision. Participants in the revised guide group performed
      significantly better on the utility task and on the Measure of Audiologic
      Rehabilitation Self-Efficacy for Hearing Aids subscales than participants in the
      original guide group. Conclusions: These results are encouraging as they indicate
      that there is scope to influence self-efficacy and utility performance through
      the use of appropriate HAUGs.

PMID- 29222576
TI  - Microbial ecology of the Agaricus bisporus mushroom cropping process.
AB  - Agaricus bisporus is the most widely cultivated mushroom species in the world.
      Cultivation is commenced by inoculating beds of semi-pasteurised composted
      organic substrate with a pure spawn of A. bisporus. The A. bisporus mycelium
      subsequently colonises the composted substrate by degrading the organic material
      to release nutrients. A layer of peat, often called "casing soil", is laid upon
      the surface of the composted substrate to induce the development of the mushroom
      crop and maintain compost environmental conditions. Extensive research has been
      conducted investigating the biochemistry and genetics of A. bisporus throughout
      the cultivation process; however, little is currently known about the wider
      microbial ecology that co-inhabits the composted substrate and casing layers. The
      compost and casing microbial communities are known to play important roles in the
      mushroom production process. Microbial species present in the compost and casing
      are known for (1) being an important source of nitrogen for the A. bisporus
      mycelium, (2) releasing sugar residues through the degradation of the wheat straw
      in the composted substrate, (3) playing a critical role in inducing development
      of the A. bisporus fruiting bodies and (4) acting as pathogens by parasitising
      the mushroom mycelium/crop. Despite a long history of research into the mushroom
      cropping process, an extensive review of the microbial communities present in the
      compost and casing has not as of yet been undertaken. The aim of this review is
      to provide a comprehensive summary of the literature investigating the compost
      and casing microbial communities throughout cultivation of the A. bisporus
      mushroom crop.

PMID- 29222575
TI  - Flexible ureteroscopy: technique, tips and tricks.
AB  - During the last decades, the surgical management of kidney stones benefited of
      many technological advances and one of them is the development of flexible
      ureteroscopy (fURS). This tool, ancillary equipment such as graspers and baskets,
      and lithotripsy technique with Holmium:YAG laser underwent many improvements
      leading to a widening of its indications with diagnostic and therapeutic
      management of upper urinary tract pathologies such as urolithiasis and urothelial
      tumors. The objective of this review is to describe the surgical technique for
      fURS as well as tips and tricks for the treatment of renal stones.

PMID- 29222578
TI  - Type 2 proatlantal intersegmental artery.

PMID- 29222577
TI  - Occupational prestige trajectory and the risk of lung and head and neck cancer
      among men and women in France.
AB  - OBJECTIVES: This study aimed at investigating the associations between
      occupational prestige trajectories and lung and head and neck (HN) cancer risk
      and to assess to what extent smoking, alcohol drinking, and occupational
      exposures contribute to these associations. METHODS: Using data from the ICARE
      case-control study (controls (2676 men/715 women), lung cancers (2019 men/558
      women), HN cancers (1793 men/305 women), we defined occupational prestige
      trajectories using group-based modeling of longitudinal data. We conducted
      logistic regression models. RESULTS: Among men, a gradient was observed from the
      downward "low to very low" trajectory to the stable very high trajectory. The
      associations were reduced when adjusting for tobacco and alcohol consumption and
      occupational exposures. Among women, when compared to the stable high trajectory,
      there was an increased cancer risk in all trajectories. The associations remained
      globally unchanged or even increased after adjustment for tobacco and alcohol
      consumption and did not change when adjusting for occupational exposures. The ORs
      were smaller for lung than for HN cancers in men. CONCLUSIONS: Occupational
      prestige trajectory is strongly associated with lung and HN cancer risk in men
      and women.

PMID- 29222579
TI  - The Deauville criteria cannot differentiate between responding and non-responding
      non-Hodgkin lymphoma patients.

PMID- 29222580
TI  - [Use of antibiotics in bones : Prophylaxis and current treatment standards].
AB  - BACKGROUND: Treatment of bone infection is difficult due the systemic
      administration of antibiotics, which means that only low concentrations reach the
      inflamed bone tissue. Loss of bone stock is common in osteomyelitis and device
      associated infection. Local antibiotics are administered in several ways for
      prophylactic purposes and also for treatment of bone infection. We intend to show
      the options and limitations of clinical use of antibiotic-loaded bone grafts.
      SUITABILITY: Bone grafts are a suitable carrier system for antibiotics. Bone
      grafts may be loaded with a variety of antimicrobial agents so that individual
      therapies may be carried out. Critical systemic side effects are unlikely even
      though extreme high drug concentrations are obtained locally, if the thresholds
      for loading with antibiotics are respected. Thus, antibiotic-loaded bone grafts
      are appropriate for prophylaxis and therapy as well. If processing is done in the
      operating theatre compliance to the legal rules must be respected. RULES: Due to
      a lack of standardised procedures for loading, application and performance of the
      application of antibiotic-loaded bone grafts medical societies are being asked to
      initiate consensus meetings in order to issue recommendations or guidelines with
      respect to antibiotic-loaded bone grafts to establish reliable rules for surgeons
      using these devices.

PMID- 29222582
TI  - Introduction to the special issue on dietary control of immunometabolism.

PMID- 29222581
TI  - Fractures in children with newly diagnosed hepatoblastoma.
AB  - BACKGROUND: Hepatoblastoma is the most common primary hepatic malignancy in
      children. We have recently noticed an increased incidence of unsuspected
      fractures in children with newly diagnosed hepatoblastoma. This association has
      been suggested in the past, but the incidence and pathophysiology remain
      uncertain. OBJECTIVE: To define the incidence and imaging features of fractures
      in children with newly diagnosed hepatoblastoma. MATERIALS AND METHODS: We
      searched the oncology database and the radiology picture archiving and
      communication system of our large tertiary care children's hospital between
      January 2000 and August 2013 for all patients who presented to our institution
      with newly diagnosed hepatoblastoma. We reviewed all available imaging exams
      (radiographs, CT scans, MRIs, and nuclear medicine studies) to identify children
      who had radiologically apparent fractures on exams during the 50 days prior to
      diagnosis or up to 2 weeks after the date of hepatoblastoma diagnosis. RESULTS:
      Forty-five children were included in this retrospective study. Eight children
      (17.8%) had fractures within 50 days prior to diagnosis or up to 2 weeks after
      the date of diagnosis, with a mean number of 4.9 fractures per patient (range 1
      13). Only 21 of the 39 fractures (54%) were diagnosed during the initial image
      interpretation. Fractures most commonly occurred in the ribs (n=21) and vertebral
      bodies (n=10). The presence of a fracture was not associated with an identified
      demographic, tumor or laboratory finding. CONCLUSION: Unsuspected fractures are
      relatively common in children with newly diagnosed hepatoblastoma.

PMID- 29222583
TI  - Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite
      induction of browning in cultured human adipocytes: a randomised, controlled
      trial in humans.
AB  - The baseline insulin data given in Table 1 for the placebo group were incorrectly
      reported as 51 +/- 10 pmol/l instead of 48 +/- 10 pmol/l. This mistake also
      impacts on data reported in Table 4.

PMID- 29222584
TI  - [Preservation of the outer ear in a complex burn injury].
AB  - Saving the outer ear in burn injuries is a challenging task for the treating
      surgeon that should not be underestimated. Burns which are initially evaluated as
      superficial, particularly in this region, often have a tendency to undergo
      progressive tissue destruction whereby conservative treatment is often no longer
      sufficient to preserve the skin of the auricle with the underlying cartilage.
      Various possibilities for saving the ear and for ear reconstruction are
      described, but in the case of severely burned patients it is often necessary to
      carry out a quick and relatively simple treatment. In the complicated case of a
      severely burned patient involving the external ear, a good cosmetic result could
      be finally obtained with preservation of form and function by means of an
      economical cartilage resection with subsequent adaptation.

PMID- 29222585
TI  - [Extranodal abdominal lymphomas].
AB  - BACKGROUND: Extranodal manifestations occur in up to 40% of non-Hodgkin
      lymphomas. The prevalence of extranodal involvement has increased. OBJECTIVES: A
      comprehensive overview on lymphoma involvement in the parenchymatous abdominal
      organs, the gastrointestinal tract, and the peritoneal cavity under due
      consideration of clinical implications is given. MATERIALS AND METHODS: A
      selective literature search with analysis of dedicated original research articles
      and reviews was carried out. Clinical guidelines are discussed. RESULTS:
      Extranodal abdominal lymphoma involvement usually occurs secondarily in advanced
      disease. Sites involved most frequently are the liver and the gastrointestinal
      tract. Extranodal abdominal lymphoma involvement is more common in the
      immunocompromised patient. CONCLUSION: Imaging findings of extranodal abdominal
      lymphoma are variable. Lymphoma is an important differential diagnosis to be
      considered in unclear tumor diseases.

PMID- 29222586
TI  - [Misty mesentery : Mesenteric panniculitis and associated processes].
AB  - BACKGROUND: Sclerosing mesenteritis (SM) and mesenteric panniculitis are rare
      processes of the mesentery which pose a major clinical and imaging challenge.
      This review article attempts to introduce a systematic nomenclature to address
      typical symptoms, imaging and major differential diagnoses. RESULTS: SM with its
      subtypes-mesenteric lipodystrophy, panniculitis and retractile mesenteritis-is a
      chronic process with a very diverse and heterogeneous clinical appearance. The
      typical radiological characteristics ("misty mesentery", increased lymph nodes,
      pseudocapsule and "fat halo") are also not very specific. A link between SM and
      malignant diseases is not proven, but there is controversial discussion.
      Therefore, if there are doubts about the diagnosis, further examinations and a
      biopsy are desired. CONCLUSION: When diagnosing SM, "red flags", i. e.
      characteristics that are atypical for SM in imaging, should be considered. In
      case of ambiguous imaging, differential diagnostics should also consider
      malignant diseases and exclude them.

PMID- 29222588
TI  - Modification of chitosan-bead support materials with L-lysine and L-asparagine
      for alpha-amylase immobilization.
AB  - Maltose syrups have got wide-range utilizations in a variety of applications from
      bakery to drug-development. alpha-Amylases are among the most widely utilized
      industrial enzymes due to their high specificity in production of maltose syrup
      from starch. However, enzymes are not stable in ex vivo conditions towards
      alteration in pH, temperature, and such other parameters as high salt
      concentrations and impurities, where immobilization is required to advance the
      stability of the enzyme with which approach the requirement of isolation of the
      enzyme from media is eliminated as well. In this study, Termamyl(r) alpha-amylase
      was immobilized on the none-modified chitosan beads (NMCB), L-lysine-modified
      chitosan beads (LMCB), and L-asparagine-modified chitosan beads (AMCB) to assess
      effects of the support material on optimum conditions and kinetic parameters of
      the alpha-amylase activity in production of maltose from starch. Immobilization
      on NMCB, LMCB, and AMCB puts a strong influence on optimum pH, optimum
      temperature, stability, and kinetic parameters of alpha-amylase. Modification of
      chitosan beads with L-lysine and L-asparagine dramatically altered the overall
      immobilization yield, and enzyme's response to pH and temperature variations and
      the kinetic parameters. AMCB provided the best immobilization yield (49%), while
      LMCB only improved the yield by 2% from 22 to 24%.

PMID- 29222587
TI  - Gastrointestinal manifestation of immunoglobulin G4-related disease:
      clarification through a multicenter survey.
AB  - BACKGROUND: Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD)
      with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4
      GID) have been published, although this entity has not been fully established
      clinicopathologically. Thus, we carried out a multicenter survey. METHODS:
      Patients with possible IgG4-GID who underwent resection were collected.
      Histologic slides were reevaluated, and eight cases with diffuse
      lymphoplasmacytic infiltration but without numerous neutrophils, granulations or
      epithelioid granulomas were further analyzed. RESULTS: Overall, the IgG4 counts
      (87-345/high-power field) and IgG4/IgG-positive ratio were high (44-115%). The
      demographic findings included advanced age among the patients (55-80 years) and
      male preponderance (six cases). Six lesions (five gastric, one esophageal),
      consisting of lymphoplasmacytic infiltration with neural involvement in the
      muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were
      histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and
      obliterative phlebitis were found in two cases, and the former gave rise to a 7
      cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co
      existed in three and two lesions, respectively. All the patients had other organ
      involvement (OOI), and serum IgG4 levels were markedly elevated (four of five
      patients). The remaining two cases with gastric IPTs featuring reactive nodular
      fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible
      cases of IgG4-RD because of the histologic findings and lack of OOI. CONCLUSIONS:
      IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer.
      Characteristic histologic findings are observed in the muscularis propria and
      gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers
      of IgG4-GID.

PMID- 29222589
TI  - Production optimization for concentration and volume-limited fed-batch reactors
      in biochemical processes.
AB  - Since a very slight violation of constraint could cause process safety and
      product quality problems in biochemical processes, an adaptive approach of fed
      batch reactor production optimization that can strictly satisfy constraints over
      the entire operating time is presented. In this approach, an improved smooth
      function is proposed such that the inequality constraints can be transformed into
      smooth constraints. Based on this, only an auxiliary state is needed to monitor
      violations in the augmented performance index. Combined with control variable
      parameterization (CVP), the dynamic optimization is executed and constraint
      violations are examined by calculating the sensitivities of states to ensure that
      the inequality constraints are satisfied everywhere inside the time interval.
      Three biochemical production optimization problems, including the manufacturing
      of ethanol, penicillin and protein, are tested as illustrations. Meanwhile,
      comparisons with pure penalty CVP method, famous dynamic optimization toolbox
      DOTcvp and literature results are carried out. Research results show that the
      proposed method achieves better performances in terms of optimization accuracy
      and computation cost.

PMID- 29222590
TI  - Technical accuracy of the integration of an external ultrasonography system into
      a navigation platform: effects of ultrasonography probe registration and target
      detection.
AB  - BACKGROUND: Intraoperative navigated ultrasonography has reached clinical
      acceptance, while published data for the accuracy of some systems are missing. We
      technically quantified and optimised the accuracy of the integration of an
      external ultrasonography system into a BrainLab navigation system. METHODS: A
      high-end ultrasonography system (Elegra; Siemens, Erlangen, Germany) was linked
      to a navigation system (Vector Vision; BrainLab, Munich, Germany). In vitro
      accuracy and precision was calculated from differences between a real world
      target (high-precision crosshair phantom) and the ultrasonography image of this
      target in the navigation coordinate system. The influence of the intrinsic
      component of the calibration phantom (for ultrasonography probe registration),
      type of target definition (manual versus automatic) and orientation of the
      ultrasound probe in relation to the navigation tracking device on accuracy and
      precision were analysed in different settings (100 measurements for each setting)
      resembling clinically relevant scenarios in the neurosurgical operating theatre.
      RESULTS: Line-of-sight angles of 45 degrees , 62 degrees  and 90 degrees  for the
      optical tracking of the navigated ultrasonography probe and a distance of 1.8 m
      revealed best accuracy and precision. Technical accuracy of the integration of
      ultrasonography into a standard navigation system is high [Euclidean error:
      median, 0.79 mm; mean, 0.89 +/- 0.42 mm for 62 degrees  angle; median range: 1.16
      1.46 mm; mean range (+/-SD): 1.22 +/- 0.32 mm to 1.46 +/- 0.55 mm for grouped
      analysis of all angles tested]. Software-based automatic target definition
      improved precision significantly (p < 0.001). CONCLUSIONS: Integration of an
      external ultrasonography system into the BrainLab navigation is accurate and
      precise. By modifying registration (and measurement conditions) via software
      modification, the in vitro accuracy and precision is improved and requirements
      for a clinical application are fully met.

PMID- 29222593
TI  - Automated ultra-high-density mapping of peri-sinus node premature atrial
      contractions.

PMID- 29222592
TI  - Circadian dependence of manual thrombus aspiration benefit in patients with ST
      segment elevation myocardial infarction undergoing primary percutaneous coronary
      intervention.
AB  - BACKGROUND: The clinical benefit of manual thrombus aspiration (TA) during
      primary percutaneous coronary intervention (PPCI) in patients with ST-segment
      elevation myocardial infarction (STEMI) remains uncertain. This study assessed
      the impact of circadian rhythms on the effectiveness of manual TA. METHODS AND
      RESULTS: We conducted an observational study of patients enrolled in the Acute
      Myocardial Infarction in Switzerland Plus registry. STEMI patients undergoing
      PPCI with (TA group) or without (PCI-alone group) manual TA were divided based on
      time-of-day symptom onset: group 1 (00:00-05:59), group 2 (06:00-11:59), group 3
      (12:00-17:59) and group 4 (18:00-23:59). The primary endpoint was circadian
      variation of myocardial infarction (MI) size. The secondary endpoint was in
      hospital all-cause mortality. Between 2009 and 2014, 3648 patients underwent PPCI
      (TA, 49%). After propensity-score matching, 2860 patients were included. Minimal
      myocardial Injury was observed in groups 2 and 3 (peak creatine kinase level
      group 1, 2723 +/- 148 U/l; group 2, 2493 +/- 105 U/l; group 3, 2550 +/- 106 U/l;
      group 4, 2952 +/- 144 U/l; p = 0.044) in the TA group, whereas no time-of-day
      dependence was found in PCI-alone group. After periodic sinusoidal regression
      analysis, a circadian relationship between time-of-day symptom onset and MI size
      was demonstrated in the TA group (p < 0.001). In-hospital all-cause mortality was
      3.4% in the TA group and 4.3% in the PCI-alone group (p = 0.20). CONCLUSIONS: In
      this large registry of STEMI patients, manual TA did not reduce in-hospital all
      cause mortality. Nonetheless, there was a circadian dependence of TA
      effectiveness with greatest myocardial salvage for patients with symptom onset
      between 06:00 and 17:59.

PMID- 29222594
TI  - Orthodontic Class II:1 treatment-efficiency and outcome quality of Herbst
      multibracket appliance therapy.
AB  - OBJECTIVES: The aim of this retrospective investigation was to assess the
      efficiency and outcome quality of Class II:1 treatment (Tx). MATERIAL AND
      METHODS: The investigation is based on the evaluation of all Class II:1 patients
      that ever (1986-2014) started Tx with a Herbst appliance and subsequently a
      multibracket appliance (MBA) at the study center. Study casts from before Tx,
      after Herbst-MBA Tx, and (if available) after >= 24 months of retention were
      evaluated using the Peer Assessment Rating (PAR) index, the Ahlgren scale, and
      standard occlusal variables. RESULTS: In total, 526 Class II:1 patients with a
      mean pre-Tx age of 14.4 years (range 9.8-44.4) had received Herbst-MBA Tx; 18
      patients discontinued Tx before completion. For 240 patients, data from >= 24
      months of retention were available. The pre-Tx PAR score of 32.4 +/- 8.83 was
      reduced to 8.0 +/- 4.51 during Tx. A slight increase to 8.8 +/- 5.11 occurred
      during retention. The percentage of patients which could be assigned to the
      category "greatly improved" was 62% after Tx and 57% after retention; only 2-3%
      had to be assigned to the category "worse/no different." The outcome ratings
      according to the Ahlgren scale revealed 17% excellent, 35% good, 45%
      satisfactory, and 3% unsuccessful results. CONCLUSIONS: Class II:1 Tx using
      Herbst-MBA is an efficient approach in orthodontic care. During a mean active Tx
      period of 2 years, high-quality results can be obtained in the majority of
      patients. CLINICAL RELEVANCE: The present investigation is the first to
      investigate a large unselected cohort of consecutive Herbst-MBA patients to
      determine representative data on the efficiency and the outcome quality of this
      Tx approach.

PMID- 29222595
TI  - 'Prostate Cancer Risk Calculator' mobile applications (Apps): a systematic review
      and scoring using the validated user version of the Mobile Application Rating
      Scale (uMARS).
AB  - PURPOSE: The use of mobile phone applications (Apps) has modernised the
      conventional practice of medicine. The diagnostic ability of the current Apps in
      prostate specific antigen monitoring, and its diagnostic ability within prostate
      cancer (PCa) risk calculators have not yet been appraised. We aimed to review,
      rate and assess the everyday functionality, and utility of all the currently
      available PCa risk calculator Apps. METHODS: A systematic search on iTunes,
      Google Play Store, Blackberry World and Windows Apps Store, was performed on
      23/11/2017, using the search term 'prostate cancer risk calculator'. After
      applying the exclusion criteria, each App was individually assessed and rated
      using pre-set criteria and grading was performed using the validated uMARS scale.
      RESULTS: In total, 83 Apps were retrieved. After applying our exclusion criteria,
      only 9 Apps were relevant, with 2 duplicated, and the remaining 7 were suitable
      for critical review. Data sizes ranged from 414 kb to 10.1 Mb. The cost of the
      Apps ranged from South African rand (ZAR) 0.00 to ZAR 29.99. The overall mean
      category uMARS scores ranged from 2.8/5 to 4.5/5. Apps such as Rotterdam Prostate
      Cancer Risk Calculator, Coral-Prostate Cancer Nomogram Calculator and CPC Risk
      Calculator, performed the best. CONCLUSIONS: The current PCa risk calculator
      mobile Apps available may be beneficial in counselling the concerned at risk
      patient. These Apps have potential to assist both the patient and the urologist
      alike. The PCa risk calculator App 'predictability' may be further enhanced by
      the incorporation of newly validated risk factors and predictors for PCa.

PMID- 29222596
TI  - The effects of local forearm muscle cooling on motor unit properties.
AB  - PURPOSE: Muscle cooling impairs maximal force. Using needle electromyography
      (EMG) to assess motor unit properties during muscle cooling, is limited and
      equivocal. Therefore, we aimed to determine the impact of local muscle cooling on
      motor unit firing properties using surface EMG decomposition. METHODS: Twenty
      participants (12 M, 8 F) completed maximal, evoked, and trapezoidal contractions
      during thermoneutral and cold muscle conditions. Forearm muscle temperature was
      manipulated using 10-min neutral (~ 32  degrees C) or 20-min cold (~ 3  degrees
      C) water baths. Twitches and maximal voluntary contractions were performed prior
      to, and after, forearm immersion in neutral or cold water. Motor unit properties
      were assessed during trapezoidal contractions to 50% baseline force using surface
      EMG decomposition. RESULTS: Impaired contractile properties from muscle cooling
      were evident in the twitch amplitude, duration, and rate of force development
      indicating that the muscle was successfully cooled from the cold water bath (all
      d >= 0.5, P < 0.05). Surface EMG decomposition showed muscle cooling increased
      the number of motor units (d = 0.7, P = 0.01) and motor unit action potential
      (MUAP) duration (d = 0.6, P < 0.001), but decreased MUAP amplitude (d = 0.2, P =
      0.012). Individually, neither motor unit firing rates (d = 0.1, P = 0.843) nor
      recruitment threshold (d = 0.1, P = 0.746) changed; however, the relationship
      between the recruitment threshold and motor unit firing rate was steeper (d =
      1.0, P < 0.001) and had an increased y-intercept (d = 0.9, P = 0.007) with muscle
      cooling. CONCLUSIONS: Since muscle contractility is impaired with muscle cooling,
      these findings suggest a compensatory increase in the number of active motor
      units, and small but coupled changes in motor unit firing rates and recruitment
      threshold to produce the same force.

PMID- 29222597
TI  - Incongruence in treatment decision making is associated with lower health-related
      quality of life among prostate cancer survivors: results from the PiCTure study.
AB  - PURPOSE: We investigated associations between treatment decision making (TDM) and
      global health-related-quality-of-life (gHRQoL) among prostate cancer (PCa)
      survivors. METHODS: Postal questionnaires were sent to 6559 PCa survivors 2-18
      years post-diagnosis, identified through population-based cancer registries in
      Ireland. The Control Preference Scale was used to investigate respondents'
      'actual' and 'preferred' role in TDM. The TDM experience was considered
      'congruent' when actual and preferred roles matched and 'incongruent' otherwise.
      The EORTC QLQ-C30 was used to measure gHRQoL. Multivariate linear regression was
      employed to investigate associations between (i) actual role in TDM, (ii)
      congruence in TDM, and gHRQoL. RESULTS: The response rate was 54% (n = 3348). The
      percentages of men whose actual role in TDM was active, shared or passive were
      36, 33 and 31%, respectively. Congruence between actual and preferred roles in
      TDM was 58%. Actual role in TDM was not associated with gHRQoL. In multivariate
      analysis, after adjusting for socio-demographic and clinical factors, survivors
      whose TDM experience was incongruent had significantly lower gHRQoL than those
      who had a congruent experience (- 2.25 95%CI - 4.09, - 0.42; p = 0.008). This
      effect was most pronounced among survivors who had more involvement in the TDM
      than they preferred (- 2.69 95%CI - 4.74, - 0.63; p = 0.010). CONCLUSIONS: Less
      than 6 in 10 PCa survivors experienced congruence between their actual and
      preferred roles in TDM. Having an incongruent TDM experience was associated with
      lower gHRQoL among survivors. These findings suggest that involving patients in
      TDM to the degree to which they want to be involved may help improve PCa
      survivors' gHRQoL.

PMID- 29222598
TI  - Information needs of adolescent and young adult cancer patients and their parent
      carers.
AB  - PURPOSE: This study aimed to explore health-related information needs of
      adolescent and young adults (AYAs) and their parent-carers and to examine
      demographic and clinical variables associated with unmet information needs,
      including patient activation. METHODS: In a national cross-sectional study, 196
      Australian AYAs diagnosed with cancer between 15 and 25 years and within 24
      months of diagnosis and 204 parent-carers reported on total and unmet needs for
      cancer and health-related information. Fifty-one percent of AYAs were male, 81%
      had completed treatment and 86% were treated in adult hospitals. RESULTS: AYAs
      and parents reported high levels of total need for information. The mean number
      of unmet needs was 5.63 and 6.82 for AYAs and parents, respectively. AYAs
      reported the highest unmet needs in relation to their cancer (e.g. late effects
      and cancer recurrence, and having children in the future). The highest unmet
      parent information needs were related to medical information about their child as
      well as information on financial issues for their children and themselves. Unmet
      information need was associated with psychological distress (posttraumatic stress
      symptoms) for AYAs and parents. Patient activation was negatively associated with
      unmet information needs for AYAs. Demographic and treatment variables were not
      significantly associated with information needs. CONCLUSION: These findings
      indicate the importance of information needs for AYAs and their carers. The
      association between patient activation and information needs suggests that
      promoting young people's engagement with healthcare is a key opportunity within
      AYA care. Parent information needs and associated emotional distress additionally
      highlight the importance of family-centered care.

PMID- 29222599
TI  - Cigarette Smoke Induces Activation of Polymorphonuclear Leukocytes.
AB  - INTRODUCTION: Cigarette smoking is a major risk factor for chronic obstructive
      pulmonary disease (COPD). Exposure to cigarette smoke may stimulate inflammatory
      response and activate polymorphonuclear leukocytes (PMN) thus resulting in
      secretion of cellular proteases. The aim of our study was to explore the effect
      of cigarette smoke extract (CSE) on the release of matrix metalloproteinase-9
      (MMP-9) from PMN. METHODS: The study included 23 patients with stable COPD and 9
      healthy controls. PMN were isolated from blood of all participants and exposed to
      4% CSE or basal culture medium (0% CSE) for 20 h. MMP-9 concentration in PMN
      culture media was measured using the ELISA method. RESULTS: Exposure of PMN to 4%
      CSE did not cause cytotoxic effects, as determined by no changes in lactate
      dehydrogenase (LDH) activity in PMN culture media when compared to untreated PMN
      (P = 0.689). In basal conditions, PMN of COPD patients released significantly
      more MMP-9 compared with PMN of healthy controls (P = 0.016). However,
      concentration ratio of MMP-9 released from PMN exposed to 4% CSE or 0% CSE of
      each participant was significantly higher for healthy subjects than for COPD
      patients (P = 0.025). CONCLUSION: Cigarette smoke induces activation of PMN in
      healthy controls. However, chronically activated PMN in COPD patients could not
      be further stimulated by in vitro exposure to CSE. Constantly raised amount of
      MMP-9 released into the tissues may be involved in the degradation of
      extracellular matrix in the lungs as seen in COPD patients.

PMID- 29222600
TI  - Pregnancy in rheumatoid arthritis: a retrospective study.

PMID- 29222601
TI  - Monitoring small pioneer trees in the forest-tundra ecotone: using multi-temporal
      airborne laser scanning data to model height growth.
AB  - Monitoring of forest resources through national forest inventory programmes is
      carried out in many countries. The expected climate changes will affect trees and
      forests and might cause an expansion of trees into presently treeless areas, such
      as above the current alpine tree line. It is therefore a need to develop methods
      that enable the inclusion of also these areas into monitoring programmes.
      Airborne laser scanning (ALS) is an established tool in operational forest
      inventories, and could be a viable option for monitoring tasks. In the present
      study, we used multi-temporal ALS data with point density of 8-15 points per m2,
      together with field measurements from single trees in the forest-tundra ecotone
      along a 1500-km-long transect in Norway. The material comprised 262 small trees
      with an average height of 1.78 m. The field-measured height growth was derived
      from height measurements at two points in time. The elapsed time between the two
      measurements was 4 years. Regression models were then used to model the
      relationship between ALS-derived variables and tree heights as well as the height
      growth. Strong relationships between ALS-derived variables and tree heights were
      found, with R 2 values of 0.93 and 0.97 for the two points in time. The
      relationship between the ALS data and the field-derived height growth was weaker,
      with R 2 values of 0.36-0.42. A cross-validation gave corresponding results, with
      root mean square errors of 19 and 11% for the ALS height models and 60% for the
      model relating ALS data to single-tree height growth.

PMID- 29222591
TI  - Dementia with Lewy bodies and Parkinson's disease-dementia: current concepts and
      controversies.
AB  - Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although
      sharing many clinical, neurochemical and morphological features, according to DSM
      5, are two entities of major neurocognitive disorders with Lewy bodies of unknown
      etiology. Despite considerable clinical overlap, their diagnosis is based on an
      arbitrary distinction between the time of onset of motor and cognitive symptoms:
      dementia often preceding parkinsonism in DLB and onset of cognitive impairment
      after onset of motor symptoms in PDD. Both are characterized morphologically by
      widespread cortical and subcortical alpha-synuclein/Lewy body plus beta-amyloid
      and tau pathologies. Based on recent publications, including the fourth consensus
      report of the DLB Consortium, a critical overview is given. The clinical features
      of DLB and PDD include cognitive impairment, parkinsonism, visual hallucinations,
      and fluctuating attention. Intravitam PET and post-mortem studies revealed more
      pronounced cortical atrophy, elevated cortical and limbic Lewy pathologies (with
      APOE epsilon4), apart from higher prevalence of Alzheimer pathology in DLB than
      PDD. These changes may account for earlier onset and greater severity of
      cognitive defects in DLB, while multitracer PET studies showed no differences in
      cholinergic and dopaminergic deficits. DLB and PDD sharing genetic,
      neurochemical, and morphologic factors are likely to represent two subtypes of an
      alpha-synuclein-associated disease spectrum (Lewy body diseases), beginning with
      incidental Lewy body disease-PD-nondemented-PDD-DLB (no parkinsonism)-DLB with
      Alzheimer's disease (DLB-AD) at the most severe end, although DLB does not begin
      with PD/PDD and does not always progress to DLB-AD, while others consider them as
      the same disease. Both DLB and PDD show heterogeneous pathology and
      neurochemistry, suggesting that they share important common underlying molecular
      pathogenesis with AD and other proteinopathies. Cognitive impairment is not only
      induced by alpha-synuclein-caused neurodegeneration but by multiple regional
      pathological scores. Recent animal models and human post-mortem studies have
      provided important insights into the pathophysiology of DLB/PDD showing some
      differences, e.g., different spreading patterns of alpha-synuclein pathology, but
      the basic pathogenic mechanisms leading to the heterogeneity between both
      disorders deserve further elucidation. In view of the controversies about the
      nosology and pathogenesis of both syndromes, there remains a pressing need to
      differentiate them more clearly and to understand the processes leading these
      synucleinopathies to cause one disorder or the other. Clinical management of both
      disorders includes cholinesterase inhibitors, other pharmacologic and
      nonpharmacologic strategies, but these have only a mild symptomatic effect.
      Currently, no disease-modifying therapies are available.

PMID- 29222602
TI  - Endoscopic ultrasound-guided biliary drainage using a newly designed metal stent
      with a thin delivery system: a preclinical study in phantom and porcine models.
AB  - PURPOSE: This study was designed to evaluate the feasibility and safety of a
      newly designed self-expandable metal stent for endoscopic ultrasound-guided
      biliary drainage (EUS-BD) when it was delivered via three different stent
      delivery systems: a 7.5Fr delivery catheter with a bullet-shaped tip (7.5Fr
      bullet), a 7Fr catheter with a bullet-shaped tip (7Fr-bullet), or a 7Fr catheter
      with a tee-shaped tip (7Fr-tee). METHODS: This experimental study utilized a
      porcine model of biliary dilatation involving ten pigs. In the animal study,
      technical feasibility and clinical outcomes of the stent when placed with each of
      the delivery systems were examined. In addition, a phantom model was used to
      measure the resistance of these delivery systems to advancement. RESULTS: Phantom
      experiments showed that, compared with 7Fr-bullet, 7Fr-tee had less resistance
      force to the advancement of the stent delivery system. EUS-BD was technically
      successful in all ten pigs. Fistulous tract dilation was necessary in 100% (2/2),
      75% (3/4), and 0% (0/4) of the pigs that underwent EUS-BD using 7.5Fr-bullet, 7Fr
      bullet, and 7Fr-tee, respectively. There were no procedure-related complications.
      CONCLUSION: Our newly designed metal stent may be feasible and safe for EUS-BD,
      particularly when delivered by 7Fr-tee, because it eliminates the need for
      fistulous tract dilation.

PMID- 29222603
TI  - Adequacy of planctomycetes as supplementary food source for Daphnia magna.
AB  - The nutritional quality of daphnids diet can influence their growth, reproduction
      and survival. In aquatic ecosystems, bacteria can contribute significantly to
      Daphnia diet by supporting, for instances, their high needs for phosphorus. The
      laboratory feeding of the model organisms Daphnia spp. is algal based, but should
      be improved to allow their better performance. The aim of this study was to
      evaluate the potential of two planctomycetes, Gemmata obscuriglobus and
      Rhodopirellula rubra, from exponential and stationary growth phases as
      alternative or supplementary food source for Daphnia magna. The actinobacterium
      Arthrobacter sp. was used for comparison. The feeding with only bacteria showed
      the inefficacy of both planctomycetes and actinobacteria as the only food source.
      However, when used in supplement to Raphidocelis subcapitata, a decrease in the
      age of first reproduction, a significant increase in reproductive output, in
      somatic growth and in rate of population increase was found for the highest cell
      densities of bacteria tested. The typical pink coloration of these bacteria
      present in daphnids body and eggs confirmed bacterial absorption and
      metabolization of their pigment. Planctomycetes yielded better results than the
      actinobacteria Arthrobacter but G. obscuriglobus that possesses sterols did not
      induce a better performance comparatively to R. rubra. No relation could be
      established between the feeding treatments that allowed improvement of Daphnia
      performance and the different kind of Daphnia' Fatty Acid Methyl Esters. The use
      of sonication to separate planctomycetal cells before feeding the daphnids proved
      to be efficient. We confirmed that R. subcapitata supplemented by bacteria allows
      a better growth performance of D. magna.

PMID- 29222604
TI  - Model based analysis of the heterogeneity in the tumour size dynamics
      differentiates vemurafenib, dabrafenib and trametinib in metastatic melanoma.
AB  - PURPOSE: Explore the heterogeneity in dynamics of tumour response to vemurafenib,
      dabrafenib and trametinib using routinely collected clinical trial imaging data.
      METHODS: Time-series imaging data from the phase III studies of vemurafenib,
      dabrafenib and trametinib were collected through a data repository. A
      mathematical model based on basic mechanisms of tumour growth was placed within a
      statistical modelling framework to analyse the data. RESULTS: The analysis
      revealed: (1) existence of homogeneity in drug response and resistance
      development within a patient; (2) tumour shrinkage rate does not relate to rate
      of resistance development; (3) vemurafenib and dabrafenib, two BRAF inhibitors,
      have different variability in tumour shrinkage rates. CONCLUSIONS: Overall these
      results show how analysis of the dynamics of individual lesions can shed light on
      the within and between patient differences in tumour shrinkage and resistance
      rates, which could be used to gain a macroscopic understanding of tumour
      heterogeneity.

PMID- 29222606
TI  - Hypothalamic-Pituitary-Adrenal (HPA) Axis Functioning in Overtraining Syndrome:
      Findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS)
      EROS-HPA Axis.
AB  - BACKGROUND: Overtraining syndrome (OTS) results from excessive training load
      without adequate recovery and leads to decreased performance and fatigue. The
      pathophysiology of OTS in athletes is not fully understood, which makes accurate
      diagnosis difficult. Previous studies indicate that alterations in the
      hypothalamus-pituitary-adrenal (HPA) axis may be responsible for OTS; however,
      the data is not conclusive. This study aimed to compare, through gold standard
      and exercise-independent tests, the response of the HPA axis in OTS-affected
      athletes (OTS group) to healthy physically active subjects (ATL group) and
      healthy non-active subjects (NCS group). METHODS: Selected subjects were
      evaluated for cortisol response to a 250-MUg cosyntropin stimulation test (CST),
      cortisol and adrenocorticotropic hormone (ACTH) responses during an insulin
      tolerance test (ITT), and salivary cortisol rhythm (SCR). RESULTS: A total of 51
      subjects were included (OTS, n = 14; ATL, n = 25; and NCS, n = 12). Cortisol
      response in the CST was similar among the three groups. Conversely, mean cortisol
      response during an ITT was significantly higher in ATL (21.7 MUg/dL; increase =
      9.2 MUg/dL) compared to OTS (17.9 MUg/dL; 6.3 MUg/dL) and NCS (16.9 MUg/dL; 6.0
      MUg/dL) (p <= 0.001; p = 0.01). Likewise, median ACTH response during an ITT was
      significantly higher in ATL (91.4 pg/mL; increase = 45.1 pg/mL) compared to OTS
      (30.3 pg/mL; 9.7 pg/mL) and NCS (51.4 pg/mL; 38.0 pg/mL) (p = 0.006; p = 0.004).
      For SCR, mean cortisol 30 min after awakening was significantly higher in ATL
      (500 ng/dL) compared to OTS (323 ng/dL) and NCS (393 ng/dL) (p = 0.004). We
      identified the following cutoffs that could help exclude or confirm OTS: cortisol
      level at 30 min after awakening (exclusion = > 530 ng/dL); cortisol response to
      ITT (exclusion = > 20.5 MUg/dL; confirmation = < 17 MUg/dL or increase < 9.5
      MUg/dL); and ACTH response (exclusion = > 106 pg/mL or increase > 70 pg/mL;
      confirmation = < 35 pg/mL and increase < 14.5 pg/mL). CONCLUSION: The findings of
      the present study showed that healthy athletes disclose adaptions to exercises
      that helped improve sport-specific performance, whereas this sort of hormonal
      conditioning was at least partially lost in OTS, which may explain the decrease
      in performance in OTS.

PMID- 29222607
TI  - Static and fatigue strength of a novel anatomically contoured implant compared to
      five current open-wedge high tibial osteotomy plates.
AB  - BACKGROUND: The purpose of the present study was to compare the mechanical static
      and fatigue strength of the size 2 osteotomy plate "Activmotion" with the
      following five other common implants for the treatment of medial knee joint
      osteoarthritis: the TomoFix small stature, the TomoFix standard, the Contour
      Lock, the iBalance and the second generation PEEKPower. METHODS: Six fourth
      generation tibial bone composites underwent a medial open-wedge high tibial
      osteotomy (HTO), according to standard techniques, using size 2 Activmotion
      osteotomy plates. All bone-implant constructs were subjected to static
      compression load to failure and load-controlled cyclic fatigue failure testing,
      according to a previously defined testing protocol. The mechanical stability was
      investigated by considering different criteria and parameters: maximum forces,
      the maximum number of loading cycles, stiffness, the permanent plastic
      deformation of the specimens during the cyclic fatigue tests, and the maximum
      displacement range in the hysteresis loops of the cyclic loading responses.
      RESULTS: In each test, all bone-implant constructs with the size 2 Activmotion
      plate failed with a fracture of the lateral cortex, like with the other five
      previously tested implants. For the static compression tests the failure occurred
      in each tested implant above the physiological loading of slow walking (> 2400
      N). The load at failure for the Activmotion group was the highest (8200 N). In
      terms of maximum load and number of cycles performed prior to failure, the size 2
      Activmotion plate showed higher results than all the other tested implants except
      the ContourLock plate. The iBalance implant offered the highest stiffness (3.1
      kN/mm) for static loading on the lateral side, while the size 2 Activmotion
      showed the highest stiffness (4.8 kN/mm) in cyclic loading. CONCLUSIONS: Overall,
      regarding all of the analysed strength parameters, the size 2 Activmotion plate
      provided equivalent or higher mechanical stability compared to the previously
      tested implant. Implants with a metaphyseal slope adapted to the tibia anatomy,
      and positioned more anteriorly on the proximal medial side of the tibia, should
      provide good mechanical stability.

PMID- 29222608
TI  - The impact of subsidized private health insurance and health facility upgrades on
      healthcare utilization and spending in rural Nigeria.
AB  - This paper analyzes the quantitative impact of an intervention that provides
      subsidized low-cost private health insurance together with health facility
      upgrades in Nigeria. The evaluation, which measures impact on healthcare
      utilization and spending, is based on a quasi-experimental design and utilizes
      three population-based household surveys over a 4-year period. After 4 years, the
      intervention increased healthcare use by 25.2 percentage points in the treatment
      area overall and by 17.7 percentage points among the insured. Utilization of
      modern healthcare facilities increased after 4 years by 20.4 percentage points in
      the treatment area and by 18.4 percentage points among the insured due to the
      intervention. After 2 years of program implementation, the intervention reduced
      healthcare spending by 51% compared with baseline, while after 4 years, spending
      resumed to pre-intervention levels.

PMID- 29222605
TI  - The endocannabinoid system in cardiovascular function: novel insights and
      clinical implications.
AB  - RATIONALE: Cardiovascular disease is now recognized as the number one cause of
      death in the world, and the size of the population at risk continues to increase
      rapidly. The dysregulation of the endocannabinoid (eCB) system plays a central
      role in a wide variety of conditions including cardiovascular disorders.
      Cannabinoid receptors, their endogenous ligands, as well as enzymes conferring
      their synthesis and degradation, exhibit overlapping distributions in the
      cardiovascular system. Furthermore, the pharmacological manipulation of the eCB
      system has effects on blood pressure, cardiac contractility, and endothelial
      vasomotor control. Growing evidence from animal studies supports the significance
      of the eCB system in cardiovascular disorders. OBJECTIVE: To summarize the
      literature surrounding the eCB system in cardiovascular function and disease and
      the new compounds that may potentially extend the range of available
      interventions. RESULTS: Drugs targeting CB1R, CB2R, TRPV1 and PPARs are proven
      effective in animal models mimicking cardiovascular disorders such as
      hypertension, atherosclerosis and myocardial infarction. Despite the setback of
      two clinical trials that exhibited unexpected harmful side-effects, preclinical
      studies are accelerating the development of more selective drugs with promising
      results devoid of adverse effects. CONCLUSION: Over the last years, increasing
      evidence from basic and clinical research supports the role of the eCB system in
      cardiovascular function. Whereas new discoveries are paving the way for the
      identification of novel drugs and therapeutic targets, the close cooperation of
      researchers, clinicians and pharmaceutical companies is needed to achieve
      successful outcomes.

PMID- 29222609
TI  - Evaluating cognition in individuals with Huntington disease: Neuro-QoL cognitive
      functioning measures.
AB  - PURPOSE: Cognitive functioning impacts health-related quality of life (HRQOL) for
      individuals with Huntington disease (HD). The Neuro-QoL includes two patient
      reported outcome (PRO) measures of cognition-Executive Function (EF) and General
      Concerns (GC). These measures have not previously been validated for use in HD.
      The purpose of this analysis is to evaluate the reliability and validity of the
      Neuro-QoL Cognitive Function measures for use in HD. METHODS: Five hundred ten
      individuals with prodromal or manifest HD completed the Neuro-QoL Cognition
      measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression
      measure (PROMIS Depression). Measures of functioning The Total Functional
      Capacity and behavior (Problem Behaviors Assessment) were completed by clinician
      interview. Objective measures of cognition were obtained using clinician
      administered Symbol Digit Modalities Test and the Stroop Test (Word, Color, and
      Interference). Self-rated, clinician-rated, and objective composite scores were
      developed. We examined the Neuro-QoL measures for reliability, convergent
      validity, discriminant validity, and known-groups validity. RESULTS: Excellent
      reliabilities (Cronbach's alphas >= 0.94) were found. Convergent validity was
      supported, with strong relationships between self-reported measures of cognition.
      Discriminant validity was supported by less robust correlations between self
      reported cognition and other constructs. Prodromal participants reported fewer
      cognitive problems than manifest groups, and early-stage HD participants reported
      fewer problems than late-stage HD participants. CONCLUSIONS: The Neuro-QoL
      Cognition measures provide reliable and valid assessments of self-reported
      cognitive functioning for individuals with HD. Findings support the utility of
      these measures for assessing self-reported cognition.

PMID- 29222610
TI  - Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort:
      a multi-level infrastructure for cancer health disparities research.
AB  - PURPOSE: We characterized the neighborhood obesogenic environment in the
      Multiethnic Cohort (MEC) by examining the associations of obesity with attributes
      of the social and built environment, establishing a multi-level infrastructure
      for future cancer research. METHODS: For 102,906 African American, Japanese
      American, Latino, and white MEC participants residing predominately in Los
      Angeles County, baseline residential addresses (1993-1996) were linked to census
      and geospatial data, capturing neighborhood socioeconomic status (nSES),
      population density, commuting, food outlets, amenities, walkability, and traffic
      density. We examined neighborhood attributes and obesity (body mass index >= 30
      kg/m2) associations using multinomial logistic regression, adjusting for
      individual-level (e.g., demographics, physical activity, and diet) and
      neighborhood-level factors. RESULTS: NSES was associated with obesity among
      African Americans, Latinos, and whites (p-trend <= 0.02), with twofold higher
      odds (adjusted odds ratios, 95% confidence intervals) for living in the lowest
      versus highest quintile among African American women (2.07, 1.62-2.65), white men
      (2.11, 1.29-3.44), and white women (2.50, 1.73-3.61). Lower density of businesses
      among African American and white women and lower traffic density among white men
      were also associated with obesity (p-trends <= 0.02). CONCLUSIONS: Our study
      highlights differential impacts of neighborhood factors across racial/ethnic
      groups and establishes the foundation for multi-level studies of the neighborhood
      context and obesity-related cancers.

PMID- 29222611
TI  - Kiwifruit SVP2 controls developmental and drought-stress pathways.
AB  - KEY MESSAGE: Genome-wide targets of Actinidia chinensis SVP2 confirm roles in ABA
      and dehydration-mediated growth repression and reveal a conservation in
      mechanism of action between SVP genes of taxonomically distant Arabidopsis and a
      woody perennial kiwifruit. The molecular mechanisms underlying growth and
      dormancy in woody perennials are largely unknown. In Arabidopsis, the MADS-box
      transcription factor SHORT VEGETATIVE PHASE (SVP) plays a key role in the
      progression from vegetative to floral development, and in woody perennials SVP
      like genes are also proposed to be involved in controlling dormancy. During
      kiwifruit development SVP2 has a role in growth inhibition, with high-chill
      kiwifruit Actinidia deliciosa transgenic lines overexpressing SVP2 showing
      suppressed bud outgrowth. Transcriptomic analyses of these plants suggests that
      SVP2 mimics the well-documented abscisic acid (ABA) effect on the plant
      dehydration response. To corroborate the growth inhibition role of SVP2 in
      kiwifruit development at the molecular level, we analysed the genome-wide direct
      targets of SVP2 using chromatin immunoprecipitation followed by high-throughput
      sequencing in kiwifruit A. chinensis. SVP2 was found to bind to at least 297
      target sites in the kiwifruit genome, and potentially modulates 252 genes that
      function in a range of biological processes, especially those involved in
      repressing meristem activity and ABA-mediated dehydration pathways. In addition,
      our ChIP-seq analysis reveals remarkable conservation in mechanism of action
      between SVP genes of taxonomically distant plant species.

PMID- 29222612
TI  - How do Parents Manage Irritability, Challenging Behaviour, Non-Compliance and
      Anxiety in Children with Autism Spectrum Disorders? A Meta-Synthesis.
AB  - Although there is increasing research interest in the parenting of children with
      ASD, at present, little is known about everyday strategies used to manage problem
      behaviour. We conducted a meta-synthesis to explore what strategies parents use
      to manage irritability, non-compliance, challenging behaviour and anxiety in
      their children with ASD. Approaches included: (1) accommodating the child; (2)
      modifying the environment; (3) providing structure, routine and occupation; (4)
      supervision and monitoring; (5) managing non-compliance with everyday tasks; (6)
      responding to problem behaviour; (7) managing distress; (8) maintaining safety
      and (9) analysing and planning. Results suggest complex parenting demands in
      children with ASD and problem behaviour. Findings will inform the development of
      a new measure to quantify parenting strategies relevant to ASD.

PMID- 29222613
TI  - Broadening the Scope of Peer-Mediated Intervention for Individuals with Autism
      Spectrum Disorders.
AB  - Peer-mediated intervention (PMI) is most commonly defined as a treatment approach
      that engages typically developing peers to teach children with autism spectrum
      disorders (ASD) social skills and increase their social interactions, mainly in a
      school setting. In this letter, we address the limitations of such understanding
      of PMI and review the arguments for broadening its scope. In particular, we argue
      that there is a critical need for research on PMI that focuses on friendship,
      social participation, and well-being of adolescents and adults with ASD, as well
      as engages peers in the community settings. In conclusion, we provide a
      description of a befriending scheme for individuals with ASD to inspire future
      research and guidelines on PMI.

PMID- 29222614
TI  - A singular K-space model for fast reconstruction of magnetic resonance images
      from undersampled data.
AB  - Reconstructing magnetic resonance images from undersampled k-space data is a
      challenging problem. This paper introduces a novel method of image reconstruction
      from undersampled k-space data based on the concept of singularizing operators
      and a novel singular k-space model. Exploring the sparsity of an image in the k
      space, the singular k-space model (SKM) is proposed in terms of the k-space
      functions of a singularizing operator. The singularizing operator is constructed
      by combining basic difference operators. An algorithm is developed to reliably
      estimate the model parameters from undersampled k-space data. The estimated
      parameters are then used to recover the missing k-space data through the model,
      subsequently achieving high-quality reconstruction of the image using inverse
      Fourier transform. Experiments on physical phantom and real brain MR images have
      shown that the proposed SKM method constantly outperforms the popular total
      variation (TV) and the classical zero-filling (ZF) methods regardless of the
      undersampling rates, the noise levels, and the image structures. For the same
      objective quality of the reconstructed images, the proposed method requires much
      less k-space data than the TV method. The SKM method is an effective method for
      fast MRI reconstruction from the undersampled k-space data. Graphical abstract
      Two Real Images and their sparsified images by singularizing operator.

PMID- 29222616
TI  - Strength in Numbers.

PMID- 29222615
TI  - Knockdown expression of IL-10Ralpha gene inhibits PRRSV replication and elevates
      immune responses in PBMCs of Tibetan pig in vitro.
AB  - Increase of interleukin-10 (IL-10) induced by Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV) infection has been intensely studied to
      inhibit the anti-viral responses of host pigs. Blockade of expression of IL-10
      receptor (IL-10R) by RNA interference (RNAi) may relieve the immunosuppression
      caused by excessive IL-10 in PRRSV infection. The recombinant short hairpin
      expressing plasmid targeted to pig IL-10Ralpha was transfected into peripheral
      blood mononuclear cells of Tibetan pig (Tp-PBMCs) prior to PRRSV inoculation,
      then the replication of PRRSV and immune responses in Tp-PBMCs were evaluated.
      The recombinant interfering plasmid greatly decreased PRRSV yield. The
      transcriptional level of IL-10Ralphawas obviously inhibited by recombinant
      interfering plasmid; the expression of IL-10 was also down-regulated, while that
      of TGF-beta1 was not affected. Furthermore, the recombinant plasmid notably up
      regulated the mRNA levels of TLR3, TLR7, IFN-alpha, IFN-gamma, IL-2, IL-4, IL
      12p40 and MyD88, while that of IL-8 was apparently decreased; In addition, cell
      viability of Tp-PBMCs was clearly enhanced by the interfering recombinant
      plasmid. Our results suggest that knockdown the expression of pig IL-10Ralpha can
      evidently inhibit the PRRSV infection and enhance the anti-viral immune responses
      of pig immune cells, which may be a promising way for preventing virus infection
      and developing new effective immune-regulator to strengthen the host immunity
      against PRRS.

PMID- 29222617
TI  - Destroy to create.

PMID- 29222618
TI  - Complex sleep apnea after full-night and split-night polysomnography: the Greek
      experience.
AB  - PURPOSE: Treatment-emergent central sleep apnea (TE-CSA) is defined as the
      emergence or persistence of central respiratory events during the initiation of
      positive airway pressure (PAP) without a back-up rate in obstructive sleep apnea
      (OSA) patients and after significant resolution of obstructive events. Previous
      studies have estimated a prevalence from 0.56 to 20.3%. The aim of this study was
      to establish the prevalence of TE-CSA in a Greek adult population. METHODS: One
      thousand fifty nine patients with newly diagnosed OSA, who were referred to the
      Sleep Disorders Center of Evangelismos Hospital of Athens over an 18-month
      period, were included in this study. A split-night polysomnography (PSG), or two
      formal overnight PSGs (diagnostic and continuous PAP (CPAP) titration study),
      were performed. RESULTS: Patients with OSA were divided in two groups; the first
      group included 277 patients, who underwent two separate studies (diagnostic and
      CPAP titration study), and the second group 782 patients, who underwent split
      night studies. The prevalence of TE-CSA in the first group was 2.53% (7
      patients), and in the second group was 5.63% (44 patients). CONCLUSIONS: The
      prevalence of TE-CSA in Greece was lower compared to most previous reported
      studies. The significant variation in the prevalence of TE-CSA between different
      centers throughout the world is mainly associated with the used diagnostic
      criteria as well as methodological and technical aspects.

PMID- 29222619
TI  - Improvement in obstructive sleep apnea after a tailored behavioural sleep
      medicine intervention targeting healthy eating and physical activity: a
      randomised controlled trial.
AB  - PURPOSE: The aim of the present single-centre randomised controlled trial was to
      assess the effect of a behavioural sleep medicine (BSM) intervention on
      obstructive sleep apnea (OSA) severity in patients who have been referred for new
      treatment with continuous positive airway pressure (CPAP). METHODS: After
      baseline assessment including ventilatory and anthropometric parameters, and
      physical activity monitoring, 86 patients who were overweight (BMI >= 25) and had
      moderate-severe OSA with apnea-hypopnea index (AHI) >= 15 were randomised into a
      control group (CG; CPAP and advice about weight loss) or an experimental group
      (ExpG; CPAP and BSM intervention targeting physical activity and eating
      behaviour). The BSM intervention comprised 10 individual sessions with a
      dietician and a physiotherapist and included behaviour change techniques such as
      goal setting and self-monitoring. After 6 months, a new recording of ventilatory
      parameters was performed without CPAP. RESULTS: In ExpG, 40% (n = 14) had
      improved from severe to moderate or mild OSA or from moderate to mild OSA
      compared to 16.7% in CG (n = 6, p = 0.02). Further, a lower AHI and amount body
      fat at baseline were correlated with improvement in severity class. Being in ExpG
      implied a mean improvement in AHI by 9.7 and an odds ratio of 4.5 for improving
      in severity classification. CONCLUSIONS: The results highlight the clinical
      importance of lifestyle modifications in conjunction with CPAP treatment in
      patients with OSA.

PMID- 29222620
TI  - The Link Between Anxiety Severity and Irritability Among Anxious Youth:
      Evaluating the Mediating Role of Sleep Problems.
AB  - Although recent studies have linked pediatric anxiety to irritability, research
      has yet to examine the mechanisms through which youth anxiety may be associated
      with irritability. Importantly, sleep related problems (SRPs) have been
      associated with both child anxiety and irritability, but research has not
      considered whether the link between youth anxiety and irritability may be
      accounted for by SRPs. The present study investigated whether SRPs mediated the
      relationship between anxiety severity and irritability in a large sample of
      treatment-seeking anxious youth (N = 435; ages 7-19 years, M = 12.7; 55.1%
      female). Anxiety severity, SRPs and irritability showed significant pairwise
      associations, and the indirect effect of youth anxiety severity on irritability,
      via SRPs, was positive and significant. The present analysis is the first to
      examine youth anxiety, irritability, and SPRs in a single model in a sample of
      anxious youth, and provides preliminary evidence that SRPs partially mediate
      links between child anxiety and irritability.

PMID- 29222621
TI  - Lifespan Extension of Caenorhabditis elegans by Butyricicoccus pullicaecorum and
      Megasphaera elsdenii with Probiotic Potential.
AB  - Butyricicoccus pullicaecorum and Megasphaera elsdenii inhabit the human intestine
      and have probiotic potential. The aim of this study was to evaluate the effects
      of B. pullicaecorum and M. elsdenii on the lifespan of Caenorhabditis elegans.
      They significantly (P < 0.05) extended the lifespan of C. elegans compared with
      Escherichia coli OP50, a standard food for the worm. Analysis of age-related
      biomarkers such as lipofuscin, body size, and locomotory activity showed that
      they retarded aging. They all failed to extend the lifespan of daf-12 or dbl-1
      loss-of-function C. elegans mutants compared with E. coli OP50-fed worms.
      However, the increase in lifespan was observed in daf-16, jnk-1, pmk-1, and skn-1
      mutants. Moreover, they increased the resistance of C. elegans to a human
      pathogen, Salmonella typhimurium. In conclusion, B. pullicaecorum and M. elsdenii
      extend the lifespan of C. elegans via the transforming growth factor-beta (TGF
      beta) pathway associated with anti-inflammatory processes in the innate immune
      system.

PMID- 29222623
TI  - Tumor Infiltrating Lymphocytes in Breast Cancer Patients with Progressive Disease
      during Neoadjuvant Chemotherapy.
AB  - A minority of breast cancer (BC) patients progress during neoadjuvant
      chemotherapy (NCT). The aim of this study was to assess the value of Tumor
      infiltrating lymphocytes (TILs) in such a high-risk population where valid
      biomarkers are eagerly needed. A retrospective review identified BC patients who
      either progressed during NCT or achieved a pathologic complete response (pCR). An
      experienced BC pathologist semi-quantified stromal TILs in pre-treatment core
      biopsies using hematoxylin and eosin stained slides. The primary outcome was to
      compare the levels of TILs between the 2 groups as a continuous and categorical
      variable using the t-test and X2 test as appropriate. The secondary outcome was
      to compare survival outcomes between patients with high versus low TILs level
      using the log-rank test. Fifty patients were successfully identified and assessed
      for TILs: 21 progressed during NCT and 29 had a pCR. Patients with progressive
      disease were older with more advanced disease (p = 0.03, p = 0.0001
      respectively). A significantly lower mean level of TILs was found in patients
      with progressive disease compared to patients with pCR: 14.3% (Standard Deviation
      (SD): 16.9) versus 32.8% (SD: 31), p = 0.01). The level of TILs was neither
      associated with baseline characteristics nor with survival outcomes. BC patients
      progressing during NCT have low TILs levels compared to patients with pCR.
      Prospective studies are needed to establish the utility of TILs as early
      biomarkers of tumor response, particularly in patients with disease progression
      who need novel treatment approaches.

PMID- 29222622
TI  - Toll-Like Receptor 4 Knockdown Attenuates Brain Damage and Neuroinflammation
      After Traumatic Brain Injury via Inhibiting Neuronal Autophagy and Astrocyte
      Activation.
AB  - Toll-like receptor 4 (TLR4) has been linked to various pathophysiological
      conditions, such as traumatic brain injury (TBI). It is reported that
      posttraumatic neuroinflammation is an essential event in the progression of brain
      injury after TBI. Recent evidences indicate that TLR4 mediates glial phagocytic
      activity and inflammatory cytokines production. Thus, TLR4 may be an important
      therapeutic target for neuroinflammatory injury post-TBI. This study was designed
      to explore potential effects and underlying mechanisms of TLR4 in rats suffered
      from TBI. TBI model was induced using a controlled cortical impact in rats, and
      application of TLR4 shRNA silenced TLR4 expression in brain prior to TBI
      induction. Elevated TLR4 was specifically observed in the hippocampal astrocytes
      and neurons posttrauma. Interestingly, TLR4 shRNA decreased the concentrations of
      interleukin (IL)-1beta, IL-6, and tissue necrosis factor-alpha; alleviated
      hippocampal neuronal damage; reduced brain edema formation; and improved
      neurological deficits after TBI. Meanwhile, to further explore underlying
      molecular mechanisms of this neuroprotective effects of TLR4 knockdown, our
      results showed that TLR4 knockdown significantly inhibited the upregulation of
      autophagy-associated proteins caused by TBI. More importantly, an autophagy
      inducer, rapamycin pretreated, could partially abolish neuroprotective effects of
      TLR4 knockdown on TBI rats. Furthermore, TLR4 silencing markedly suppressed GFAP
      upregulation and improved cell hypertrophy to attenuate TBI-induced astrocyte
      activation. Taken together, these findings suggested that TLR4 knockdown
      ameliorated neuroinflammatory response and brain injury after TBI through
      suppressing autophagy induction and astrocyte activation.

PMID- 29222624
TI  - Dapsone for Recalcitrant Eosinophilic Annular Erythema: A Case Report and
      Literature Review.
AB  - Eosinophilic annular erythema (EAE) is a rare entity of unknown etiology that is
      possibly related to a hypersensitivity reaction and presents as annular
      erythematous plaques with tissue eosinophilia. It is classified as a figurate
      erythema with a controversial relationship to Wells syndrome (WS) in the
      literature, where it is generally considered a separate entity or subset based on
      clinical and histopathologic differences. EAE typically presents with recurrent,
      erythematous, arcuate, and annular plaques on the trunk and proximal extremities.
      The course of the disease is often chronic, recurrent, and relapsing. Responses
      to treatment are variable but are typically best with systemic steroids and
      antimalarials. We report a patient refractory to other therapies who had a
      striking response to dapsone.

PMID- 29222625
TI  - Using Patient Feedback to Optimize the Design of a Certolizumab Pegol
      Electromechanical Self-Injection Device: Insights from Human Factors Studies.
AB  - INTRODUCTION: We incorporated patient feedback from human factors studies (HFS)
      in the patient-centric design and validation of ava(r), an electromechanical
      device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab
      pegol (CZP). METHODS: Healthcare professionals, caregivers, healthy volunteers,
      and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing
      spondylitis, or Crohn's disease participated in 11 formative HFS to optimize the
      e-Device design through intended user feedback; nine studies involved simulated
      injections. Formative participant questionnaire feedback was collected following
      e-Device prototype handling. Validation HFS (one EU study and one US study)
      assessed the safe and effective setup and use of the e-Device using 22 predefined
      critical tasks. Task outcomes were categorized as "failures" if participants did
      not succeed within three attempts. RESULTS: Two hundred eighty-three participants
      entered formative (163) and validation (120) HFS; 260 participants performed one
      or more simulated e-Device self-injections. Design changes following formative
      HFS included alterations to buttons and the graphical user interface screen. All
      validation HFS participants completed critical tasks necessary for CZP dose
      delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in
      the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study).
      CONCLUSION: CZP e-Device development was guided by intended user feedback through
      HFS, ensuring the final design addressed patients' needs. In both validation
      studies, participants successfully performed all critical tasks, demonstrating
      safe and effective e-Device self-injections. FUNDING: UCB Pharma. Plain language
      summary available on the journal website.

PMID- 29222626
TI  - The Effect of Phacoemulsification on Intraocular Pressure in Eyes with
      Hyperfiltration Following Trabeculectomy: A Prospective Study.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of visually non
      significant cataract extraction in patients with hypotony maculopathy and reduced
      visual acuity due to over-filtering blebs after trabeculectomy. METHODS: Patients
      with intraocular pressure (IOP) < 6 mmHg and documented hypotony maculopathy due
      to over-filtering blebs after trabeculectomy were prospectively recruited.
      Eligible patients underwent visually non-significant cataract
      phacoemulsification, no earlier than 12 weeks from the diagnosis of hypotony
      maculopathy. IOP and visual acuity before and after phacoemulsification were
      compared at 1 and 3 months from surgery. Correlations between age, time interval
      between surgeries, baseline IOP, bleb type and IOP and visual acuity changes at 3
      months after phacoemulsification were investigated. RESULTS: From January 2010 to
      September 2014, 20 consecutive adult patients met the inclusion criteria. Before
      phacoemulsification, mean IOP was 3.1 +/- 1.6 mmHg. Following
      phacoemulsification, mean IOP increased to 8.6 +/- 4.1 mmHg at 1 month (p < 0.01)
      and to 9.1 +/- 4.3 mmHg at 3 months (p < 0.01). IOP elevation following
      phacoemulsification was observed in 16 of 20 eyes (80%). Mean visual acuity
      improved from Snellen 0.5 +/- 0.1 to 0.6 +/- 0.1 at 1 month (p < 0.01) to 0.7 +/-
      0.2 at 3 months (p < 0.01) after phacoemulsification. In 4 eyes in which the IOP
      was not elevated, surgical revision of the previous trabeculectomy was performed.
      No significant correlations between investigated variables, visual acuity and IOP
      changes at 3 months after phacoemulsification were found. CONCLUSION:
      Phacoemulsification of visually non-significant cataract appears to be a safe and
      effective technique for managing chronic ocular hypotony with deep anterior
      chamber due to over-filtering blebs.

PMID- 29222627
TI  - Pediatric Asthma Management in China: Current and Future Challenges.
AB  - The purpose of this report was to review the state of asthma diagnosis and
      treatment in China and to examine challenges in achieving earlier diagnosis and
      treatment. The prevalence of asthma in children in China has increased over past
      decades, and data published in 2013 indicated a prevalence of 3.0% in children
      aged 0-14 years. Although this prevalence has increased, the percentage of
      children with acute asthma attacks decreased from 86% in 2000 to 77% in 2010, and
      the frequency of hospitalizations for asthma attacks decreased from 54.0 to 47%.
      These decreases are attributed to aggressive promotion of the Global Initiative
      for Asthma (GINA) protocol and updated Chinese guidelines for the prevention and
      treatment of asthma in children. The use of inhaled corticosteroids increased and
      that of systemic corticosteroids decreased between 2000 and 2010. Despite these
      advances, a number of issues remain to be addressed. Parents lack basic knowledge
      of asthma and fear the use of corticosteroids. Physician education regarding the
      diagnosis of asthma in children aged < 6 years is lacking. Patients require
      training in the administration of inhaled corticosteroids and control of
      environmental triggers. The Chinese national guidelines for childhood asthma have
      been updated, but implementation remains a real challenge.

PMID- 29222628
TI  - One-Year Clinical Effectiveness Comparison of Prasugrel with Ticagrelor: Results
      from a Retrospective Observational Study using an Integrated Claims Database.
AB  - BACKGROUND: No direct comparisons of ticagrelor and prasugrel with 1-year
      clinical follow-up have been reported. OBJECTIVES: Our objective was to compare 1
      year clinical outcomes among patients with acute coronary syndrome (ACS) managed
      with percutaneous coronary intervention (PCI) and treated with either ticagrelor
      or prasugrel in a real-world setting. METHODS: This retrospective study included
      patients from a payer database who were aged >=18 years and had ACS managed with
      PCI with no history of transient ischemic attack (TIA)/stroke. Data were
      propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post
      discharge net adverse clinical event (NACE) rate at 1 year was evaluated for
      noninferiority using a pre-defined 20% margin. NACE was a composite of major
      adverse cardiovascular events (MACE) or rehospitalization for bleeding. RESULTS:
      In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor
      2991). Prasugrel-treated patients were younger; less likely to be female, have
      prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI
      (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated
      patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no
      difference in bleeding with prasugrel compared with ticagrelor. After matching,
      there was no significant difference in baseline characteristics. Noninferiority
      was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor.
      NACE and MACE were significantly lower with prasugrel use, primarily driven by
      heart failure, with no significant difference in all-cause death, MI, UA,
      revascularization, TIA/stroke, or bleeding. CONCLUSIONS: In this retrospective
      study, physicians preferentially used prasugrel rather than ticagrelor in younger
      ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity
      matching, clinical outcomes associated with prasugrel were noninferior to those
      with ticagrelor.

PMID- 29222629
TI  - Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation,
      Pathogenesis and Treatment.
AB  - Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis that
      develops following cutaneous inflammation. Common causes of PIH include intrinsic
      skin conditions (e.g., acne and eczema) as well as external insults to the skin,
      such as burn injuries and dermatologic procedures. PIH more commonly occurs in
      individuals with darker skin, for whom it is often a source of significant
      psychological distress. Several therapeutic modalities are available for the
      treatment of PIH, including topical agents, chemical peels, and energy-based
      devices. We review the epidemiology, clinical presentation, pathogenesis, and
      treatment of PIH.

PMID- 29222630
TI  - 'There's so much to it': the ways physiotherapy students and recent graduates
      experience practice.
AB  - Health science courses aim to prepare students for the demands of their chosen
      profession by learning ways appropriate to that profession and the contexts they
      will work and live in. Expectations of what students should learn become re
      contextualised and translated into entry-level curriculum, with students
      operating as a connection between what is intended and enacted in curriculum, and
      required in the real world. Drawing on phenomenology, this paper explores how
      students understand practice-the collective, purposeful knowing, doing and being
      of a community-in entry-level physiotherapy programs. Ways of thinking and
      practising (WTP)-a framework attentive to the distinctive nature of a discipline,
      its values, philosophies and world-view (McCune and Hounsell in High Educ
      49(3):255-289, 2005)-provides the conceptual lens. Six themes describing how
      students see the WTP of physiotherapy practice emerged from the analysis:
      discovery of new knowledge; problem solving client related contexts; adopting a
      systems based approach to the body; contributing to a positive therapeutic
      alliance; developing a sense of self and the profession; and the organisation of
      the workforce. The study produces knowledge about practice by focusing on
      physiotherapy students' experiences of disciplinary learning. Including students
      in educational research in this way is an approach that can help students realise
      their potential as part of a community of practice.

PMID- 29222631
TI  - An advanced simulator for orthopedic surgical training.
AB  - PURPOSE: The purpose of creating the virtual reality (VR) simulator is to
      facilitate and supplement the training opportunities provided to orthopedic
      residents. The use of VR simulators has increased rapidly in the field of medical
      surgery for training purposes. This paper discusses the creation of the virtual
      surgical environment (VSE) for training residents in an orthopedic surgical
      process called less invasive stabilization system (LISS) surgery which is used to
      address fractures of the femur. METHOD: The overall methodology included first
      obtaining an understanding of the LISS plating process through interactions with
      expert orthopedic surgeons and developing the information centric models. The
      information centric models provided a structured basis to design and build the
      simulator. Subsequently, the haptic-based simulator was built. Finally, the
      learning assessments were conducted in a medical school. RESULTS: The results
      from the learning assessments confirm the effectiveness of the VSE for teaching
      medical residents and students. The scope of the assessment was to ensure (1) the
      correctness and (2) the usefulness of the VSE. Out of 37 residents/students who
      participated in the test, 32 showed improvements in their understanding of the
      LISS plating surgical process. A majority of participants were satisfied with the
      use of teaching Avatars and haptic technology. A paired t test was conducted to
      test the statistical significance of the assessment data which showed that the
      data were statistically significant. CONCLUSION: This paper demonstrates the
      usefulness of adopting information centric modeling approach in the design and
      development of the simulator. The assessment results underscore the potential of
      using VR-based simulators in medical education especially in orthopedic surgery.

PMID- 29222632
TI  - Preoperative platelet-lymphocyte ratio is an independent factor of poor prognosis
      after curative surgery for colon cancer.
AB  - Interaction between tumour and host triggers a systemic inflammatory response.
      This situation has been associated to cancer progression. Several peripheral
      blood inflammatory scores have been recently developed, as PLR. Data about the
      relationship between these scores and cancer prognosis are contradictory.
      Therefore, the aim of our work is to evaluate the capability of PLR to predict
      long-term outcomes (OS and RFS) in patients who underwent curative surgery for
      colon cancer. A retrospective study was designed with patients who underwent
      curative surgery for colon cancer between September 2008 and January 2012 at Rio
      Hortega University Hospital, Valladolid (Spain). We analysed the influence of PLR
      and other clinical variables on OS and RFS. Finally, 201 patients were analysed.
      Optimal cut-off value for PLR, established with ROC curves, was 153. 1-, 3- and 5
      year OS were: 99.0, 90.4 and 82.3% for low PLR, and 93.8, 74.9 and 61.9% for high
      PLR, p < 0.001. 1-, 3- and 5-year RFS were: 92.4, 84.7 and 77.6% for low PLR, and
      83.3, 64.5 and 52.6% for high PLR, p < 0.001. In MVA, high PLR was an independent
      negative prognostic factor for OS (HR = 2.11; 95% CI 1.22-3.66; p = 0.008) and
      RFS (HR = 1.99; 95% CI 1.19-3.34; p = 0.009). PLR represents an independent
      negative prognostic factor for OS and RFS in our sample of patients who underwent
      curative surgery for colon cancer. However, further studies with a larger sample
      size from different populations are necessary to confirm this conclusion.

PMID- 29222633
TI  - Characterising youth with callous-unemotional traits and concurrent anxiety:
      evidence for a high-risk clinical group.
AB  - Growing evidence supports the existence of two variants of youth with high
      callous-unemotional (CU) traits who present with markedly different risk profiles
      and outcomes, with potential implications for risk assessment and treatment
      formulation. So far, studies have identified variants of CU youth mainly using
      data-driven cluster approaches based on levels of CU traits and co-occurring
      anxiety. Yet, the extent to which this knowledge may be translated into clinical
      practice is unclear. To this end, the present study employed a severity-based,
      cut-off approach to systematically characterise CU groups across a range of
      clinically informative domains, including trauma history, psychiatric
      symptomatology, affective functioning, attachment style and behavioural risk.
      Analyses were based on multi-rated data from a community sample of high-risk
      youths (n = 155, M = 18 years). Consistent with previous studies, we found that,
      whereas variants show comparable levels of antisocial behaviour, those who
      present with both high CU and high anxiety report more severe childhood
      maltreatment, psychological distress, ADHD symptomatology and behavioural risk
      including substance use, suicidal ideation and unsafe sex. In addition, these
      youth show greater attachment insecurity and affective dysregulation, as indexed
      by levels of irritability and alexithymia. Together, findings indicate that (1)
      trauma history is a key factor that differentiates variants of CU youth high vs.
      low on anxiety, and (2) differences in individual functioning across variants
      point to the need for tailored clinical assessment tools and intervention
      strategies. Importantly, the present findings indicate that variants of CU youth
      can be meaningfully differentiated using cut-off based approaches that parallel
      methods used in clinical assessments.

PMID- 29222635
TI  - Cardiovascular Response of Rat Aorta to Di-(2-ethylhexyl) Phthalate (DEHP)
      Exposure.
AB  - Phthalates are one of the main constituents of plastic, reaching up to 40% of the
      total plastic weight, and their main function is to impart flexibility/elasticity
      to polymers that would otherwise be rigid. Phthalates are known as endocrine
      disruptors, since they can interfere with hormone homeostasis. Regarding the
      cardiovascular system, it was already shown the effects of di-(2-ethylhexyl)
      phthalate (DEHP) exposure with significant changes in several calcium-handling
      proteins and an increase in the blood pressure of mice offspring, suggesting that
      DEHP leads to vasocontraction. However, the mechanisms involved were not
      elucidated yet. The aim of this study is to analyse the involvement of calcium
      channels in the effects induced by DEHP on vascular smooth muscle cells.
      Endothelium-denuded aorta artery rings were prepared from male Wistar rats and
      incubated in an organ bath, and the whole-cell configuration of Patch Clamp
      technique was used to measure the activity of L-type Ca2+ channels (LTCC) in A7r5
      cells. Overall, DEHP caused relaxation on KCl-induced contraction at higher
      concentrations and inhibited the basal and BAY K8644-stimulated calcium current,
      indicating that this drug blocks LTCC. These results suggest that DEHP induces
      relaxation on vascular smooth muscle cells due to the inhibition of calcium
      channels.

PMID- 29222634
TI  - What is the level of evidence for the use of currently available technologies in
      facilitating the self-management of difficulties associated with ADHD in children
      and young people? A systematic review.
AB  - A number of technologies to help self-manage attention deficit hyperactivity
      disorder (ADHD) in children and young people (YP) have been developed. This
      review will assess the level of evidence for the use of such technologies. The
      review was undertaken in accordance with the general principles recommended in
      the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. 7545
      studies were screened. Fourteen studies of technology that aim to self-manage
      difficulties associated with ADHD in children and YP were included. Primary
      outcome measures were measures that assessed difficulties related to ADHD.
      Databases searched were MEDLINE, Web of Science (Core collection), CINAHL, the
      Cochrane Library, ProQuest ASSIA, PsycINFO and Scopus. The methodological quality
      of the studies was assessed. This review highlights the potential for the use of
      technology in paediatric ADHD management. However, it also demonstrates that
      current research lacks robustness; using small sample sizes, non-validated
      outcome measures and little psychoeducation component. Future research is
      required to investigate the value of technology in supporting children and YP
      with ADHD and a focus psychoeducation is needed.

PMID- 29222636
TI  - Identification, introgression, and molecular marker genetic analysis and
      selection of a highly effective novel oat crown rust resistance from diploid oat,
      Avena strigosa.
AB  - KEY MESSAGE: Oat crown rust is one of the most damaging diseases of oat. We
      identified a new source of resistance and developed KASP and TaqMan markers for
      selection in breeding programs. A new highly effective resistance to oat crown
      rust (Puccinia coronata f. sp. avenae) was identified in the diploid oat Avena
      strigosa PI 258731 and introgressed into hexaploid cultivated oat. Young plants
      with this resistance show moderate susceptibility, whereas older plant tissues
      and adult plants are resistant with no virulent isolates encountered in over 8
      years of testing. Resistance was incorporated into hexaploid oat by embryo
      rescue, colchicine chromosome doubling followed by backcrosses with a hexaploid
      parent, and selection for stable transmission of resistance. To mitigate flag
      leaf and panicle chlorosis/necrosis associated with the resistance, crosses were
      made with derived resistant lines to breeding lines of divergent parentage
      followed by selection. Subsequently, two F2 sister lines, termed MNBT1020-1 and
      MNBT1021-1, were identified in which the chlorosis/necrosis was reduced. These
      two lines performed well in replicated multi-location state trials in 2015 and
      2016 out-yielding all cultivar entries. Segregating F2:3 plants resulting from
      crosses of MNBT lines to susceptible parents were genotyped with the oat 6K SNP
      array, and SNP loci with close linkage to the resistance were identified. KASP
      assays generated from linked SNPs showed accurate discrimination of the
      resistance in derivatives of the resistant MNBT lines crossed to susceptible
      breeding lines. A TaqMan marker was developed and correctly identified homozygous
      resistance in over 95% of 379 F4 plants when rust was scored in F4:5 plants in
      the field. Thus, a novel highly effective resistance and associated molecular
      markers are available for use in breeding, genetic analysis, and functional
      studies.

PMID- 29222637
TI  - Coffee consumption and risk of hypertension: a dose-response meta-analysis of
      prospective studies.
AB  - PURPOSE: Recently, a large prospective study provided additional information
      concerning the debated possible association between habitual coffee consumption
      and risk of hypertension (HPT). Therefore, we updated the state of knowledge on
      this issue by carrying out a comprehensive new systematic review of the
      literature and a meta-analysis of the available relevant studies. METHODS: We
      performed a systematic search for prospective studies on general population,
      published without language restrictions (1966-August 2017). A random-effects dose
      response meta-analysis was conducted to combine study specific relative risks
      (RRs) and 95% confidence intervals. Potential non-linear relation was
      investigated using restricted cubic splines. RESULTS: Four studies (196,256
      participants, 41,184 diagnosis of HPT) met the inclusion criteria. Coffee intake
      was assessed by dietary questionnaire. Dose-response meta-analysis showed a non
      linear relationship between coffee consumption and risk of HPT (p for non
      linearity < 0.001). Whereas the habitual drinking of one or two cups of coffee
      per day, compared with non-drinking, was not associated with risk of HPT, a
      significantly protective effect of coffee consumption was found starting from the
      consumption of three cups of coffee per day (RR = 0.97, 95% CI = 0.94 to 0.99),
      and was confirmed for greater consumption. CONCLUSIONS: The results of this
      analysis indicate that habitual moderate coffee intake is not associated with
      higher risk of HPT in the general population and that in fact a non-linear
      inverse dose-response relationship occurs between coffee consumption and risk of
      HPT.

PMID- 29222638
TI  - Meat intake and incidence of cardiovascular disease in Japanese patients with
      type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS).
AB  - PURPOSE: Excessive meat intake has been researched as a major cause of
      cardiovascular disease (CVD) among healthy adults, but data on this topic in
      Asian patients with diabetes are sparse. The quantity and variety of available
      meats vary widely between Asian and Western countries. As part of a nationwide
      cohort study we investigated the relationship between meat intake and incidence
      of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c >=
      6.5%. METHODS: Analyzed were 1353 responders to a baseline dietary survey
      assessed by the Food Frequency Questionnaire based on food groups. Primary
      outcome was the 8-year risk of a CVD event, including coronary heart disease
      (CHD) and stroke. Cox regression analyses estimated hazard ratios (HRs) for
      dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy
      intake, and other confounders. RESULTS: Mean meat intake in quartiles ranged from
      9.9 to 97.7 g/day. After adjusting for confounders, HRs of CHD in the 2nd, 3rd,
      and 4th quartiles for meat intake compared with the 1st quartile were 2.84 (95%
      confidence interval 1.29-6.24, p = 0.01), 3.02 (1.36-6.70, p < 0.01), and 2.99
      (1.35-6.65, p = 0.01), respectively. In two groups according to meat intake,
      patients consuming >= 20 g/day of meat had a 2.94-fold higher risk of CHD than
      those consuming < 20 g/day (p < 0.01). There was no significant association of
      stroke with meat intake. CONCLUSIONS: An elevated incidence of CHD in Japanese
      patients with type 2 diabetes was associated with high meat intake.

PMID- 29222639
TI  - Sleep-Related Painful Erections Following Sexual Intercourse.
AB  - Sleep-related painful erections (SRPE) is a rare disorder characterized by
      recurrent painful nocturnal erections during REM sleep in the absence of pain
      during daytime erections. Approximately 35 cases of SRPE have been reported in
      the literature, none of them associated with preceding sexual intercourse. We add
      the report of a 40-year-old patient with a 6-year history of SRPE which only, but
      always, occurred after sexual intercourse with ejaculation in the evening before.
      As a result, the frequency of intercourse diminished, causing relationship
      problems. A non-pharmacological solution was found in shifting the time of sexual
      intercourse. The patient refused any proposed pharmacological treatment, because
      of "not wanting to be a patient at his age."

PMID- 29222640
TI  - Clinical effect of emergency cervical cerclage and elective cervical cerclage on
      pregnancy outcome in the cervical-incompetent pregnant women.
AB  - PURPOSE: To compare the clinical effect of emergency cervical cerclage and
      elective cervical cerclage on pregnancy outcome in the cervical-incompetent
      pregnant women. METHODS: Literature was searched from the databases of Pubmed,
      Embase and Google scholar. The fixed or random effects model was used to
      calculate pooled risk ratios on the basis of heterogeneity. Meta-regression,
      sensitive analysis, subgroup analysis, and publication bias assessment were also
      conducted to confirm the results according to Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses 2009. RESULTS: The meta-analysis results
      showed that there were significant associations between cerclage operations and
      pregnancy outcomes in gestation age, birth weight, and PROM rate. Gestation age
      was significantly higher in women with elective cerclage than those with
      emergency cerclage, and birth weight was significantly higher in newborns for the
      elective group as compared with emergency group. The rate of PROM in elective
      group was lower than emergency group. However, there were no differences between
      the emergency cerclage group and the elective cerclage group regarding the rate
      of vaginal delivery. CONCLUSIONS: This meta-analysis suggests that emergency
      cerclage has lower gestation age and birth weight than elective cerclage, and it
      increases the risk of PROM. Further well-designed studies are warranted to
      confirm these results.

PMID- 29222641
TI  - Bipolar vessel-sealing devices in laparoscopic hysterectomies: a multicenter
      randomized controlled clinical trial.
AB  - OBJECTIVE: To compare operating time and blood loss in patients undergoing total
      laparoscopic hysterectomies (TLH) for benign conditions with either the MarsealTM
      IQ 5 mm (MS) or the LigasureTM 5 mm (LS) vessel-sealing device. DESIGN AND
      SETTING: A randomized controlled clinical trial (RCT) in two German gynecology
      departments. PATIENTS: 74 patients scheduled to undergo TLH for a symptomatic
      fibroid uterus, adenomyosis or severe meno-metrorrhagia. INTERVENTIONS: Patients
      were randomized to receive a TLH with either the MS or the LS device. 27
      variables were prospectively collected to address potential confounding issues.
      MEASUREMENT AND MAIN RESULTS: Operating time, defined as the time period between
      the first (round ligament dissection) and the last (uterine vessels sealing) use
      of the device, estimated and calculated intraoperative blood loss. The mean
      operating time (95% confidence interval, CI) was 22.7 min (95% CI 17.6-27.7) for
      LS and 26.4 min (95% CI 20-32.8) for the MS device (p = .89). The estimated
      intraoperative blood loss was 164 ml (95% CI 110-217) for LS and 160 ml (95% CI
      116-203) for the MS device (p = .36). The multivariate analyses accounting for
      BMI, endometriosis, uterine weight and appearance of fibroids did not reveal any
      significant effect of the type of device used on operating time and estimated
      blood loss. CONCLUSION: In this RCT, both devices provided reliable and effective
      sealing and dissection. The reusable MS showed non-inferiority against the
      disposable LS device with regard to operating time and estimated intraoperative
      blood loss.

PMID- 29222642
TI  - Pituitary adenomas, stem cells, and cancer stem cells: what's new?
AB  - PURPOSE: To clarify the existence of pituitary stem cells (SCs) both in the
      embryonic and the postnatal gland and the role for SCs in pituitary adenomas.
      METHODS: This work, which does not address the pathogenesis of pituitary
      adenomas, reviews the latest research findings and discoveries on SCs in
      pituitary and cancer SCs (CSCs) in pituitary adenomas and discusses the
      involvement of the EMT. RESULTS: Several groups using different approaches and
      techniques have demonstrated the existence of SCs and CSCs and as they are major
      players in pituitary adenoma onset. CONCLUSIONS: As in other benign and malignant
      tumors, the hypothesis that CSCs play a pivotal role in pituitary adenoma onset
      has been confirmed as well as the existence of a link between the epithelial-to
      mesenchymal transition (EMT) process and CSC formation in epithelial tumors.

PMID- 29222643
TI  - Overexpression of SIRT2 Alleviates Neuropathic Pain and Neuroinflammation Through
      Deacetylation of Transcription Factor Nuclear Factor-Kappa B.
AB  - Sirtuin 2 (SIRT2), a member of the mammalian sirtuin family, plays an important
      role in the pathogenesis of various neurological diseases. However, whether SIRT2
      is involved in the regulation of neuropathic pain remains unclear. In this study,
      we aimed to investigate the potential role of SIRT2 in regulating neuropathic
      pain in a rat model induced by chronic constriction injury (CCI). We found that
      SIRT2 was downregulated in the dorsal root ganglion (DRG) in CCI rats.
      Intrathecal injection of a recombinant adenovirus expressing SIRT2 markedly
      alleviated mechanical allodynia and thermal hyperalgesia in CCI rats. This also
      inhibited the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and IL-6 in the DRG of CCI rats. Moreover, our results showed
      that overexpression of SIRT2 inhibited the acetylation of the nuclear factor
      kappa B (NF-kappaB) p65 protein in the DRG of CCI rats. Additionally, treatment
      with a SIRT2 specific inhibitor significantly aggravated neuropathic pain and
      attenuated the inhibitory effect of SIRT2 overexpression on neuropathic pain
      development. Taken together, these results suggest that overexpression of SIRT2
      alleviates neuropathic pain associated with inhibition of NF-kappaB signaling and
      neuroinflammation. Therefore, SIRT2 may serve as a potential therapeutic target
      for treatment of neuropathic pain.

PMID- 29222644
TI  - Membrane-shed vesicles from the parasite Trichomonas vaginalis: characterization
      and their association with cell interaction.
AB  - Trichomonas vaginalis is a common sexually transmitted parasite that colonizes
      the human urogenital tract, where it remains extracellular and adheres to
      epithelial cells. Infections range from asymptomatic to highly inflammatory,
      depending on the host and the parasite strain. Despite the serious consequences
      associated with trichomoniasis disease, little is known about parasite or host
      factors involved in attachment of the parasite-to-host epithelial cells. Here, we
      report the identification of microvesicle-like structures (MVs) released by T.
      vaginalis. MVs are considered universal transport vehicles for intercellular
      communication as they can incorporate peptides, proteins, lipids, miRNA, and
      mRNA, all of which can be transferred to target cells through receptor-ligand
      interactions, fusion with the cell membrane, and delivery of a functional cargo
      to the cytoplasm of the target cell. In the present study, we demonstrated that
      T. vaginalis release MVs from the plasma and the flagellar membranes of the
      parasite. We performed proteomic profiling of these structures demonstrating that
      they possess physical characteristics similar to mammalian extracellular vesicles
      and might be selectively charged with specific protein content. In addition, we
      demonstrated that viable T. vaginalis parasites release large vesicles (LVs),
      membrane structures larger than 1 um that are able to interact with other
      parasites and with the host cell. Finally, we show that both populations of
      vesicles present on the surface of T vaginalis are induced in the presence of
      host cells, consistent with a role in modulating cell interactions.

PMID- 29222646
TI  - Evidence for the involvement of opioid system in the antidepressant-like effect
      of ascorbic acid.
AB  - Considering the involvement of the opioid system in major depressive disorder
      (MDD), mainly concerning refractory MDD, and the evidence that ascorbic acid may
      exert a beneficial effect for the treatment of this disorder, this study
      investigated the involvement of the opioid system in the antidepressant-like
      effect of ascorbic acid in the tail suspension test (TST). Treatment of Swiss
      mice with the non-selective opioid receptor antagonist naloxone (1 mg/kg, i.p.)
      prevented the reduced immobility time caused by ascorbic acid (1 mg/kg, p.o.) in
      the TST. Additionally, administration of the selective MU1-opioid receptor
      antagonist, naloxonazine (10 mg/kg, i.p.), also abolished the antidepressant-like
      action of the same dose of ascorbic acid in the TST. We also investigated the
      possible relationship between the opioid system and NMDA receptors in the
      mechanism of action of ascorbic acid or ketamine (0.1 mg/kg, i.p.) in the TST.
      Treatment of mice with naloxone (1 mg/kg, i.p.) blocked the synergistic
      antidepressant-like effect of ascorbic acid (0.1 mg/kg. p.o.) and MK-801 (0.001
      mg/kg, p.o., a non-competitive NMDA receptor antagonist) in the TST. Combined
      administration of ketamine and MK-801 induced a synergistic antidepressant-like
      action, and naloxone partially abolished this effect. Our results indicate that
      the antidepressant-like effect of ascorbic acid in the TST appears to be
      dependent on the activation of the opioid system, especially MU1-opioid
      receptors, which might be an indirect consequence of NMDA receptor inhibition
      elicited by ascorbic acid administration.

PMID- 29222648
TI  - The Level of Toxic Elements in Edible Crops from Seleniferous Area (Punjab,
      India).
AB  - The primary objective of the present study was to assess the level of selenium
      and toxic trace elements in wheat, rice, maize, and mustard from seleniferous
      areas of Punjab, India. The content of selenium (Se) and toxic trace elements,
      including aluminum (Al), arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni),
      lead (Pb), and tin (Sn), in crop samples was assessed using inductively coupled
      plasma mass-spectrometry after microwave digestion of the samples. The obtained
      data demonstrate that cultivation of crops on seleniferous soils significantly
      increased Se level in wheat, mustard, rice, and maize by a factor of more than
      590, 111, 85, and 64, respectively. The study also showed that Se exposure
      affected toxic metal content in crops. In particular, Se-rich wheat was
      characterized by a significant decrease in Al, As, Ni, Pb, and Sn levels. The
      level of As, Cd, Ni, Pb, and Sn was significantly decreased in Se-rich rice,
      whereas As content was increased. In turn, the decrease in Al, As, Cd, Ni, Pb,
      and Sn levels in Se-rich maize was associated with a significant elevation of Hg
      content. Finally, Se-rich mustard was characterized by a significant increase in
      Al, As, and Hg levels, while the content of Ni, Pb, and Sn was significantly
      lower than the control levels. These findings should be taken into account while
      developing the nutritional strategies for correction of Se status. At the same
      time, the exact mechanisms underlying the observed differences are to be
      estimated.

PMID- 29222645
TI  - Role of the microenvironment in myeloid malignancies.
AB  - The bone marrow microenvironment (BMM) regulates the fate of hematopoietic stem
      cells (HSCs) in homeostatic and pathologic conditions. In myeloid malignancies,
      new insights into the role of the BMM and its cellular and molecular actors in
      the progression of the diseases have started to emerge. In this review, we will
      focus on describing the major players of the HSC niche and the role of the
      altered niche function in myeloid malignancies, more specifically focusing on the
      mesenchymal stroma cell compartment.

PMID- 29222647
TI  - Bevacizumab for recurrent, persistent or advanced cervical cancer:
      reproducibility of GOG 240 study results in "real world" patients.
AB  - PURPOSE: Bevacizumab is the only therapeutic target approved for patients with
      persistent, recurrent or advanced cervical cancer from a phase III study that
      combined with chemotherapy; it proves a significant increase in overall survival.
      To retrospectively assess the efficacy and safety of bevacizumab as the first
      line treatment in patients from usual clinical practice with recurrent/persistent
      or advanced cervical cancer. PATIENTS AND METHODS: Treatment consisted of
      cisplatin 50 mg/m2 or carboplatin AUC 5 plus paclitaxel 175 mg/m2 for 6-8 cycles
      and bevacizumab 15 mg/kg every 3 weeks up to progression or unacceptable
      toxicity. The endpoints were progression-free survival (PFS), overall survival
      (OS), response rates (RR) and toxicity. RESULTS: Twenty-seven patients were
      included from January 2014 to June 2017, with a median follow-up 10, 1 months.
      Eleven percent had recurrent/persistent disease and 89% had metastatic disease at
      diagnosis. The prior exposition to platinum was 70%. The median PFS and OS were
      9, 6 and 21, 5 months, respectively. There was an increase of fistula formation
      (22%). All of them had pelvic and peritoneal disease at the beginning of
      treatment and previous treatment with chemoradiotherapy; non-incidence
      differences were found according to the type of platinum agent used. There were
      two treatment-related deaths, one from intestinal perforation and another from
      severe sepsis. CONCLUSION: Finally, although our study does have certain
      limitations, we believe that it can provide useful information and encouraging
      evidence that the routine use of bevacizumab as part of first-line treatment of
      patients with advanced cervical cancer may be associated with outcomes comparable
      with those obtained in GOG240 study.

PMID- 29222649
TI  - Effect of Oral Zinc Supplementation on the Thiol Oxido-Reductive Index and Thiol
      Related Enzymes in Seminal Plasma and Spermatozoa of Iraqi Asthenospermic
      Patients.
AB  - A thiol group plays an essential role in sperm metabolism and the antioxidative
      defense state. Zinc is the second most abundant element in the human body,
      following iron. The present study was conducted to study the effect of zinc
      supplementation on the characteristics of semen along with thiol and thiol
      related enzymes in semen of asthenospermic patients. Semen samples were obtained
      from 60 fertile and 60 asthenospermic men, from couples who had consulted the
      infertility clinic of Babil Hospital (Hillah city, Iraq). The subfertile group
      was treated with zinc; every participant took two 220 mg capsules of zinc sulfate
      per day for 3 months. Semen samples were obtained (before and after zinc
      supplementation). The levels of reduced thiol, oxidized thiol, thiol oxido
      reductive index, and thiol-related enzymes activities were determined in
      spermatozoa and seminal plasma of patients and healthy groups. Oxidized thiol
      levels were significantly higher in the infertile patients compared to that in
      the fertile group. Conversely, reduced thiol level, sulfhydryl oxidase activity,
      and glutathione peroxidase activity significantly decreased in the infertile
      patients compared to that in the fertile group. Oxidized thiol levels, reduced
      thiol levels, and thiol-related enzymes activities of the infertile patients were
      restored to normal values after treatment with zinc. However, reduced and
      oxidized thiol levels in spermatozoa did not change significantly in the group
      treated with zinc. The quantitative values for RSH/RSSR and thiol-related enzymes
      may provide useful means to qualitatively express the oxidant/antioxidant balance
      in clinical and epidemiologic studies. ClinicalTrials.gov Identifier:
      NCT02985905.

PMID- 29222651
TI  - Grandmothers and Children's Schooling in Sub-Saharan Africa.
AB  - Under poor circumstances, co-residence of a grandmother is generally considered
      to be beneficial for (grand)children. Empirical evidence does not unequivocally
      support this expectation and suggests that the grandmother's importance depends
      on the family's circumstances. We study the relationship between grandmother's co
      residence and children's schooling in sub-Saharan Africa under a broad range of
      circumstances. Results make clear that the effect of a co-residing grandmother
      varies but is almost always positive. Grandmothers over age 60 are most effective
      in helping their (grand)children. They are particularly important for girls, and
      when the mother is deceased or not living in the household. Grandmothers are less
      effective in situations with few opportunities, as in very poor regions or in
      communities with few schooling opportunities. Our findings indicate that
      providing support to grandmothers should not be overlooked when designing
      policies aimed at strengthening the position of women and children in the sub
      Saharan African context.

PMID- 29222650
TI  - Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage
      IV neck node-positive head and neck cancer and a good performance status.
AB  - PURPOSE: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF)
      induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell
      carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well
      tolerated when given with prophylactic treatment against predicted adverse
      effects and which patients benefit most. METHODS: A single-centre audit
      identified 132 HNSCC patients with stage IVa/b neck node-positive disease,
      prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2
      IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2-5.
      Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with
      concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and
      22). All patients received prophylactic antibiotics and granulocyte colony
      stimulating factor. RESULTS: Median follow-up was 39.5 months. 92.4% of patients
      completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade
      3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related
      deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%;
      locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those
      without locoregional recurrence). Good performance status (p = 0.002) and poor
      tumour differentiation (p = 0.018) were associated with improved overall survival
      on multivariate analysis. CONCLUSION: With prophylactic antibiotics and
      granulocyte colony-stimulating factor TPF was well tolerated with good survival
      outcomes. TPF should remain a treatment option for stage IV neck node-positive
      patients with a good performance status. The use of tumour grade to aid patient
      selection for TPF warrants investigation.

PMID- 29222653
TI  - Ultrasensitive colorimetric detection of NF-kappaB protein at picomolar levels
      using target-induced passivation of nanoparticles.
AB  - We developed a highly sensitive and selective sensor based on the nanoprobe
      conjugates of catalytic nanoparticles and double-stranded DNA (dsDNA) for the
      colorimetric detection of NF-kappaB protein. The sensing mechanism takes
      advantage of the catalytic activity of nanoparticle surfaces and the specific
      binding of NF-kappaB to a dsDNA sequence. In the presence of NF-kappaB, the
      highly selective interactions between dsDNA and NF-kappaB lead to the passivation
      of the catalytic nanoparticle surfaces, impeding the sodium borohydride-mediated
      reduction rate of 4-nitrophenol. The correlation between the NF-kappaB
      concentration and the visualized reduction rate of 4-nitrophenol from yellow to
      colorless clearly demonstrates the highly quantitative nature of the sensor.
      Importantly, this sensor can conclusively detect concentrations as low as 6.39 pM
      of NF-kappaB, which to best of our knowledge is the lowest limit of detection for
      a colorimetric NF-kappaB detection system. The excellent sensitivity of this
      sensor relies on the high binding constant of NF-kappaB to dsDNA and the
      catalytic activity of nanoparticle surfaces for the signal amplification. This
      sensor allows visual detection without the need for any spectrometric
      instrumentation. We also determined the various parameters such as the pH,
      temperature, incubation time, and salt concentration for optimal NF-kappaB-dsDNA
      interactions. Finally, we demonstrated the performance of the sensor with
      simulated sample analysis. Graphical abstract A highly sensitive and selective
      colorimetric detection of protein NF-kappaB using the nanoprobeconjugates of
      catalytic gold nanoparticles and double-stranded DNA (dsDNA) has been developed.

PMID- 29222652
TI  - Development of a kelp powder (Thallus laminariae) Standard Reference Material.
AB  - A Standard Reference Material (SRM) of seaweed, SRM 3232 Kelp Powder (Thallus
      laminariae) has been developed to support food and dietary supplement
      measurements in compliance with the Food Safety Modernization Act (FSMA) and the
      Dietary Supplement Health and Education Act of 1994 (DSHEA). The material was
      characterized for nutritional minerals, arsenic species, isomers of vitamin K1,
      proximates, and toxic elements. Kelp is a rich source of vitamins and minerals,
      and it is an excellent source of dietary iodine. Kelp also contains a large
      amount of arsenic, which is toxic as inorganic species but much less so as
      organic species. To capture the dietary profile of kelp, certified values were
      issued for As, Ca, Cd, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Mo, Na, Pb, and Zn.
      Reference values for proximates were assigned. For the first time, a certified
      value for iodine, reference values for isomers of vitamin K1, and reference
      values for arsenic species including arsenosugars were assigned in a seaweed. SRM
      3232 fills a gap in Certified Reference Materials (CRMs) needed for quality
      assurance and method validation in the compositional measurements of kelp and
      similar seaweeds used as food and as dietary supplements. Graphical Absract
      Arsenic species and isomers of vitamin K1 were determined in the development of
      SRM 3232 Kelp Powder (Thallus laminariae).

PMID- 29222654
TI  - Determination of total phthalate in cosmetics using a simple three-phase sample
      preparation method.
AB  - A simple sample preparation method requiring minimal organic solvents is proposed
      for the determination of the total phthalate content in cosmetics by high
      performance liquid chromatography-tandem mass spectrometry. The hydrolysis of
      phthalates and purification of interfering substances were performed in a three
      phase system that included an upper n-hexane phase, a middle ethanol phase, and a
      lower aqueous alkali solution. This three-phase system utilized an incremental
      purification strategy. The apolar ingredients were extracted with n-hexane, the
      polar pigments accumulated in the ethanol phase, and the hydrolysis product,
      phthalic acid, remained in the hydrolysate. Under the optimized conditions, the
      correlation coefficients (r) for the calibration curves were 0.998-0.999 in the
      range 0.60-12 mol L-1. The limit of detection was 5.1 MUmol kg-1, and the limit
      of quantification was 9.2 MUmol kg-1. The recoveries varied from 84 to 97% with
      RSDs equal to or lower than 11%. The intra-day and inter-day repeatability
      values, expressed as the relative standard deviation, were less than 8.7 and 9.8,
      respectively. No obvious matrix effect existed in the different cosmetics
      matrices. The validated method was applied for the analysis of 57 commercial
      cosmetic samples. Graphical abstract Analysis of phthalates in cosmetics using a
      three-phase preparation method.

PMID- 29222655
TI  - Levels, dietary intake, and health risk of potentially toxic metals in
      vegetables, fruits, and cereal crops in Pakistan.
AB  - Food safety is a major concern worldwide and human beings are frequently exposed
      to potentially toxic metals (PTMs) through consumption of vegetables, fruits, and
      cereal crops grown in contaminated areas. The present study investigates the
      concentrations of PTMs such as chromium (Cr), nickel (Ni), zinc (Zn), arsenic
      (As), cadmium (Cd), and lead (Pb) in the foodstuffs (fruits, vegetables, and
      cereals) collected from different markets of Khyber Pakhtunkhwa, Pakistan.
      Samples of fruits (banana, tangerine, apple, and guava), vegetables (tomato,
      onion, potato, pea, and lady finger), and cereals (rice, kidney beans, and chick
      peas) were acid-extracted and analyzed using ICP-MS. The concentrations of Cr,
      Zn, Pb, As, and Cd in fruits (54, 50, 50, 45, and 4% samples, respectively),
      vegetables (53, 43, 63, 80, and 46%), and cereals (37, 62, 25, 70, and 25%)
      exceeded their respective permissible limits set by FAO/WHO (2001). The results
      showed that the highest mean concentration was observed for Ni (14.95 mg/kg), Pb
      (0.57 mg/kg), and Cd (0.27 mg/kg) in vegetables followed by fruits and cereals.
      However, the highest mean concentration of As (0.44 mg/kg) was observed in cereal
      crops followed by vegetables and fruits. The individual health risk of PTMs via
      consumption of fruits, vegetables, and cereals were found within safe limits for
      adults and children. Nevertheless, the total HRI values (fruits + vegetables +
      cereals) for Ni, As, and Cd for both adults and children were observed > 1 and
      may posed potential risk for the community consuming these foodstuffs on a daily
      basis. Graphical abstract ?.

PMID- 29222656
TI  - Changes to tetracyclines and tetracycline resistance genes in arable soils after
      single and multiple applications of manure containing tetracyclines.
AB  - The influence of manure containing tetracyclines (TCs) on the prevalence of
      antibiotic resistance genes in soils remains poorly understood. Here, three
      different TCs (oxytetracycline (OTC), tetracycline (TC), and chlortetracycline
      (CTC)) were mixed respectively with unpolluted manure to fertilize arable soil.
      The soil received either a single application of 0 MUg kg-1, 300 MUg kg-1 (TC and
      CTC), or 700 MUg kg-1 (OTC) or multiple applications every 14 days for 140 days.
      Four tetracycline resistance genes (TRGs), including tet(A), tet(L), tet(M), and
      tet(Q), were monitored. Although the abundances of the four TRGs in the single
      application treatment initially increased rapidly, they decreased over time and
      were significantly lower than those of the repeated treatments after day 112. All
      additions of TCs stopped on day 140, but we continued to assess the long-term
      accumulation of TRGs. Most of the TRGs were detected even after the TC-containing
      manures had not been applied for more than 15 months. The abundance of the TRGs
      after ceasing fertilization with the TC-containing manures was higher in the
      repeated application treatments than in the single application treatments.
      Therefore, more attention should be paid to repeated applications of antibiotic
      containing manure to arable soils.

PMID- 29222657
TI  - Protective effects of fucoxanthin and fucoxanthinol against tributyltin-induced
      oxidative stress in HepG2 cells.
AB  - Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms,
      which has been used for decades for industrial purposes. Fucoxanthin is a natural
      carotenoid that is isolated from seaweed, and fucoxanthinol is a major primary
      metabolite of fucoxanthin. Although fucoxanthin and fucoxanthinol have been
      reported to possess anti-oxidant activities in vitro, little is known as to
      whether they protect against TBT-induced oxidative stress in cultured cells. In
      the present study, the protective effect of fucoxanthin and fucoxanthinol against
      oxidative stress induced by TBT was investigated. The data showed that incubation
      of HepG2 cells with 0.2 MUM TBT significantly increased cell apoptosis, whereas
      treatment with fucoxanthin or fucoxanthinol (3 MUM) significantly recovered cell
      viability. In addition, fucoxanthinol treatment significantly decreased the
      intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in HepG2
      cells incubated with TBT. Moreover, fucoxanthin and fucoxanthinol markedly
      increased the expression level of Bcl-2/Bax. These results demonstrated that both
      fucoxanthin and fucoxanthinol effectively prevented cytotoxicity in HepG2 cells
      treated with TBT, and the protective effect was likely associated with decreased
      intracellular ROS and MDA and increased Bcl-2/Bax levels.

PMID- 29222658
TI  - Phytotoxic effects of silver nanoparticles in tobacco plants.
AB  - The small size of nanoparticles (NPs), with dimensions between 1 and 100 nm,
      results in unique chemical and physical characteristics, which is why they are
      implemented in various consumer products. Therefore, an important concern is the
      potential detrimental impact of NPs on the environment. As plants are a vital
      part of ecosystem, investigation of the phytotoxic effects of NPs is particularly
      interesting. This study investigated the potential phytotoxicity of silver
      nanoparticles (AgNPs) on tobacco (Nicotiana tabacum) plants and compared it with
      the effects of the same AgNO3 concentrations. Accumulation of silver in roots and
      leaves was equally efficient after both AgNP and AgNO3 treatment, with
      predominant Ag levels found in the roots. Exposure to AgNPs did not result in
      elevated values of oxidative stress parameters either in roots or in leaves,
      while AgNO3 induced oxidative stress in both plant tissues. In the presence of
      both AgNPs and AgNO3, root meristem cells became highly vacuolated, which
      indicates that vacuoles might be the primary storage target for accumulated Ag.
      Direct AgNP uptake by root cells was confirmed. Leaf ultrastructural studies
      revealed changes mainly in the size of chloroplasts of AgNP-treated and AgNO3
      treated plants. All of these findings indicate that nano form of silver is less
      toxic to tobacco plants than silver ions.

PMID- 29222659
TI  - Municipal solid waste compost as a novel sorbent for antimony(V): adsorption and
      release trials at acidic pH.
AB  - The ability of two municipal solid waste composts (MSW-Cs) to sorb antimony(V) in
      acidic conditions (pH 4.5) was investigated. Sorption isotherms and kinetics
      showed that both MSW-Cs could sorb antimony(V), even if in different amounts (~
      0.18 and 0.24 mmol g-1 of Sb(V) by MSW-C1 and MSW-C2, respectively). These
      differences were ascribed to the chemical composition of composts, as well as to
      the total acidity of their humic substances. The Sb(V) sorption by both MSW-Cs
      followed a pseudo-second-order kinetic model, while the sorption isotherms data
      fitted the Freundlich model better than the Langmuir one. The humic acids
      extracted from composts contributed to 4.26 and 8.24% of Sb(V) sorption by MSW-C1
      and MSW-C2 respectively. SEM-EDX spectra of the MSW-C+Sb(V) systems showed a
      certain association of Ca(II) with Sb(V), while sequential extraction procedures
      indicated that more than 80% of the Sb(V) sorbed was strongly retained by MSW-Cs.
      On the other hand, treatment with oxalic acid at pH 4.5 favored the release of
      more than 98 and 65% of the Sb(V) sorbed by MSW-C1 and MSW-C2 respectively,
      supporting a possible role of calcium in Sb(V) retention. The results from this
      study suggest that MSW-Cs could be used as amendments for the in-situ
      immobilization of Sb(V) in acidic-polluted soils.

PMID- 29222660
TI  - Testing the role of fiscal policy in the environmental degradation: the case of
      Turkey.
AB  - This study introduces a new research topic that investigates the relationship
      between fiscal development and carbon emissions in Turkey through testing
      Environmental Kuznets Curve (EKC) hypothesis. Annual data covering the period,
      1960-2013, has been used and in addition to gross domestic product and energy
      consumption, fiscal policy variables have been regressed on the level of carbon
      emissions in Turkey. Results reveal that fiscal policies and carbon emissions are
      in long-term equilibrium relationship in Turkey; carbon dioxide emission level
      converges towards long-term paths as contributed by fiscal policy. The effects of
      fiscal aggregates on the level of carbon dioxide emissions are negatively
      significant revealing that growth in fiscal aggregates leads to declines on the
      levels of carbon emissions. This proves that as far as environmental effects are
      concerned, fiscal policies regarding energy sector is successful in Turkey. Thus,
      the major finding of this study confirmed the validity of the fiscal policy
      induced EKC hypothesis in the case of Turkey.

PMID- 29222661
TI  - CFD modeling of hydro-biochemical behavior of MSW subjected to leachate
      recirculation.
AB  - The most commonly used method of operating landfills more sustainably is to
      promote rapid biodegradation and stabilization of municipal solid waste (MSW) by
      leachate recirculation. The present study is an application of computational
      fluid dynamics (CFD) to the 3D modeling of leachate recirculation in bioreactor
      landfills using vertical wells. The objective is to model and investigate the
      hydrodynamic and biochemical behavior of MSW subject to leachate recirculation.
      The results indicate that the maximum recirculated leachate volume can be reached
      when vertical wells are set at the upper middle part of a landfill (H W/H T =
      0.4), and increasing the screen length can be more helpful in enlarging the
      influence radius than increasing the well length (an increase in H S/H W from 0.4
      to 0.6 results in an increase in influence radius from 6.5 to 7.7 m). The time to
      reach steady state of leachate recirculation decreases with the increase in
      pressure head; however, the time for leachate to drain away increases with the
      increase in pressure head. It also showed that methanogenic biomass inoculum of
      1.0 kg/m3 can accelerate the volatile fatty acid depletion and increase the peak
      depletion rate to 2.7 * 10-6 kg/m3/s. The degradation-induced void change
      parameter exerts an influence on the processes of MSW biodegradation because a
      smaller parameter value results in a greater increase in void space.

PMID- 29222662
TI  - Enhanced activity and stability of La-doped CeO2 monolithic catalysts for lean
      oxygen methane combustion.
AB  - Effective utilization of coal bed methane is very significant for energy
      utilization and environment protection. Catalytic combustion of methane is a
      promising way to eliminate trace amounts of oxygen in the coal bed methane and
      the key to this technology is the development of high-efficiency catalysts.
      Herein, we report a series of Ce1-xLaxO2-delta (x = 0-0.8) monolithic catalysts
      for the catalytic combustion of methane, which are prepared by citric acid
      method. The structural characterization shows that the substitution of La enhance
      the oxygen vacancy concentration and reducibility of the supports and promote the
      migration of the surface oxygen, as a result improve the catalytic activity of
      CeO2. M-Ce0.8La0.2O2-delta (monolithic catalyst, Ce0.8La0.2O2-delta coated on
      cordierite honeycomb) exhibits outstanding activity for methane combustion, and
      the temperature for 10 and 90% methane conversion are 495 and 580  degrees C,
      respectively. Additionally, Ce0.8La0.2O2-delta monolithic catalyst presents
      excellent stability at high temperature. These Ce1-xLaxO2-delta monolithic
      materials with a small amount of La incorporation therefore show promises as
      highly efficient solid solution catalysts for lean-oxygen methane combustion.
      Graphical abstract ?.

PMID- 29222663
TI  - Magnetic ethylene diamine-functionalized graphene oxide as novel sorbent for
      removal of lead and cadmium ions from wastewater samples.
AB  - In this paper, magnetic ethylene diamine-functionalized graphene oxide (MDFGO) as
      a novel sorbent was synthesized and applied for removal of Pb(II) and Cd(II) from
      real wastewater samples. The morphology and molecular structure of MDFGO were
      studied by different analytical methods. The effective parameters in adsorption
      efficiency of Pb(II) and Cd(II) were studied and optimized using experimental
      design. Under the optimal condition, the effective parameters including pH,
      sorbent dosage, shaking rate, and adsorption time were 6.2, 33.0 mg, 500 rpm, and
      11 min, respectively. Mechanism of adsorption kinetic was investigated using the
      Lagergren pseudo-first-order, pseudo-second-order, and intraparticle diffusion
      models. It was found that adsorption of lead and cadmium ions in the MDFGO
      sorbent followed from pseudo-first-order and pseudo-second-order models,
      respectively. Thermodynamic parameters (DeltaG degrees , DeltaH degrees , and
      DeltaS degrees ) for the lead and cadmium ions uptake onto the MDFGO sorbent were
      calculated and indicated that the adsorption processes were spontaneous and
      endothermic in nature for both cations. In order to investigate the isotherm
      model for adsorption of Pb(II) and Cd(II), the experimental data were studied
      using the Langmuir, Freundlich, and Harkins-Jura isotherm models. The results
      fitted well with Freundlich model for both metal ions. The new sorbent (MDFGO)
      was applied to remove Pb(II) and Cd(II) from battery wastewater and
      electroplating wastewater. The removal percentage of Pb(II) and Cd(II) were
      99.6+/-0.5 and 99.4+/-0.6, respectively, and demonstrated that the new sorbent
      was very suitable for removal of lead and cadmium ion from the real wastewater
      samples.

PMID- 29222664
TI  - Anatomical reconstruction to treat acromion fractures following reverse shoulder
      arthroplasty.
AB  - PURPOSE: Scapular fractures after reverse shoulder arthroplasty (RSA) are often
      associated with substantial shoulder impairment. Patient outcomes following
      either conservative or operative treatment have not been favourable, and
      consensus is lacking on the best treatment approach. We describe a technique for
      anatomic reconstruction of fractured lateral and basal acromion in patients at
      higher risk for diminished function or those for which conservative treatment has
      already failed. METHODS: Of the 95 patients who underwent RSA at our institution
      between December 2013 and December 2016, three had post-operative acromion
      fractures (type II). Two of these patients had secondary dislocation and one
      underwent conservative treatment that failed. In all three cases, the acromion
      was reconstructed using an open technique with plate and interfragmentary screw
      fixation. RESULTS: After the acromial fracture and prior to reconstructive
      surgery, the shoulder function decreased substantially in all three cases.
      Following reconstruction, forward flexion improved from 53.0 degrees  to 127
      degrees , and abduction improved from 52.0 to 125 degrees . The range of the
      Constant scores at the one year follow-up was 55-71, and the subjective shoulder
      value (SSV) was 50-90. One patient reached the same active range of motion (ROM)
      as her pre-fracture status, and the two other patients improved but did not
      regain the previous ROM level. CONCLUSION: Acromion fractures after RSA are
      serious complications that have the potential to cause severe shoulder function
      impairment. Our fixation technique for anatomic lateral and basal acromion
      reconstruction was used safely to treat three patients with poor shoulder
      function due to secondary dislocation or non-unions.

PMID- 29222665
TI  - Small but diverse: larval trematode communities in the small freshwater
      planorbids Gyraulus albus and Segmentina nitida (Gastropoda: Pulmonata) from the
      Ruhr River, Germany.
AB  - In contrast to the well-studied trematode fauna of lymnaeid snails, only little
      is known about the role of small planorbid snails as first intermediate hosts for
      trematodes in temperate freshwater systems. This study aims at closing this gap
      by assessing the diversity and composition of larval trematode communities in
      Gyraulus albus and Segmentina nitida in a Central European reservoir system, and
      by providing an updated comprehensive review of the published trematode records
      of these snail hosts. A total of 3691 planorbid snails (3270 G. albus; 421 S.
      nitida) was collected in three consecutive years from four reservoirs of the
      River Ruhr catchment area in Germany. Gyraulus albus showed a higher overall
      trematode prevalence (11.7%) and more diverse trematode fauna (12 species)
      compared to S. nitida, which harboured three species and showed a lower trematode
      prevalence (1.7%). Altogether, 13 trematode species belonging to four families
      were identified in both hosts. Seven trematode species encountered in this study
      represent novel records for these hosts, and/or constitute first records of these
      larval stages from Germany. Trematode component communities in G. albus were
      stable across seasons and years, indicating excellent conditions for trematodes
      in this snail host and the continuous presence of the final hosts of the most
      dominant trematode species. Overall, this study reveals the importance of small
      planorbid snails, in particular G. albus, as first intermediate hosts for a
      species-rich trematode fauna in European freshwater systems, and highlights the
      parasites' contribution to the ecosystem's biodiversity.

PMID- 29222666
TI  - Morphometric variation in Periglischrus torrealbai (Acari: Spinturnicidae) on
      three species of host bats (Chiroptera: Phyllostomidae) with a new record of host
      species.
AB  - We evaluated morphometric variation of the mite Periglischrus torrealbai
      (Spinturnicidae) on three species of host bats: Phyllostomus discolor, P.
      hastatus, and Tonatia bidens (Phyllostomidae). A total of 67 females and 74 males
      of P. torrealbai were collected from 41 host individuals of these three bat
      species that were sampled in Brazil, Paraguay, and Peru. Twenty-one measurements
      from the dorsal side and 28 from the ventral side were recorded from female mites
      and 21 dorsal and 34 ventral measurements were taken from males. To evaluate
      morphological variation of P. torrealbai on different species of host bats,
      principal component analysis and unweighted pair-group method using arithmetic
      averages cluster analysis with Euclidean distances were used. Both analyses
      showed three groups of mites clearly separated: group 1 comprised all
      ectoparasites collected from T. bidens, group 2 included all mites from P.
      hastatus, and group 3 had all those from P. discolor. This result indicates that
      P. torrealbai varies morphologically by host bat species and suggests that this
      nominal species comprises three morphologically distinct species. In the present
      study, we record for the first time, the association between P. torrealbai and T.
      bidens. Our data reinforce the high relationship of specificity between
      Periglischrus mites and phyllostomid bat species.

PMID- 29222667
TI  - Drug Burden and its Association with Falls Among Older Adults in New Zealand: A
      National Population Cross-Sectional Study.
AB  - BACKGROUND: Adverse outcomes associated with advanced diseases are often
      exacerbated by polypharmacy. OBJECTIVES: The current study investigated an
      association between exposure to anticholinergic and sedative medicines and falls
      in community-dwelling older people, after controlling for potential confounders.
      METHODS: We conducted a retrospective cross-sectional study of a continuously
      recruited national cohort of community-dwelling New Zealanders aged 65 years and
      over. Participants had an International Resident Assessment Instrument-Home Care
      (interRAI-HC) assessment between 1 September 2012 and 31 January 2016. InterRAI
      HC is a comprehensive, multi-domain, standardised assessment. This study captured
      18 variables, including fall frequency, from the interRAI. These data were
      deterministically matched with the Drug Burden Index (DBI) for each participant,
      derived from an anonymised national dispensed pharmaceuticals database. DBI
      groupings were statistically ascertained, and ordinal regression models employed.
      RESULTS: Overall, there were 71,856 participants, with a mean age of 82.7 years
      (range 65-106); 43,802 (61.0%) were female, and 63,578 (88.5%) were New Zealand
      European. In unadjusted and adjusted analyses, DBI groupings were related to
      falls (p < 0.001). A DBI score > 3 was associated with a 41% increase in falls
      compared with a DBI score of 0 (p < 0.001). There was a 'dose-response'
      relationship between DBI levels and falls risk. CONCLUSIONS: DBI was found to be
      independently and positively associated with a greater risk of falls in this
      cohort after adjustment for 18 known confounders. We suggest that the DBI could
      be a valuable tool for clinicians to use alongside electronic prescribing to help
      reduce falls in older people.

PMID- 29222668
TI  - Responsibility for scientific misconduct in collaborative papers.
AB  - This paper concerns the responsibility of co-authors in cases of scientific
      misconduct. Arguments in research integrity guidelines and in the bioethics
      literature concerning authorship responsibilities are discussed. It is argued
      that it is unreasonable to claim that for every case where a research paper is
      found to be fraudulent, each author is morally responsible for all aspects of
      that paper, or that one particular author has such a responsibility. It is
      further argued that it is more constructive to specify what task responsibilities
      come with different roles in a project and describe what kinds of situations or
      events call for some kind of action, and what the appropriate actions might be.

PMID- 29222669
TI  - The preoperative HbA1c level is an independent prognostic factor for the
      postoperative survival after resection of non-small cell lung cancer in elderly
      patients.
AB  - PURPOSE: The aim of this study was to investigate the influence of a history of
      diabetes mellitus (DM) and the glycated hemoglobin (HbA1c) level on the survival
      in patients who underwent complete resection for non-small cell lung cancer
      (NSCLC). METHODS: Of the patients who underwent complete resection for NSCLC
      between 2007 and 2015, 468 were classified into DM (who were currently taking
      medication for DM) and no DM groups as well as into high HbA1c (>= 6.5) and
      normal HbA1c (< 6.5) groups. RESULTS: The overall survival (OS) did not differ
      significantly between either pair of groups. Among the elderly patients, the OS
      did not differ significantly between the DM and no DM groups, but was
      significantly higher in the normal-HbA1c group than in the high-HbA1c group (5
      year survival rate: 84.7 versus 37.2%, respectively, p < 0.01). In the elderly
      patients, non-adenocarcinoma histology, advanced stage, a high Charlson
      comorbidity index, and a high preoperative HbA1c level were found to be
      independent risk factors for the OS. CONCLUSION: We revealed that a high
      preoperative HbA1c level was associated with a poor OS in elderly patients who
      underwent complete resection for NSCLC. This suggests that it is necessary to
      achieve diabetic control prior to complete resection in NSCLC patients.

PMID- 29222670
TI  - Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group
      Perspective of a NICE Single Technology Appraisal.
AB  - Venetoclax is licensed to treat relapsed or refractory (R/R) chronic lymphocytic
      leukaemia (CLL). As part of the Single Technology Appraisal (STA) ID944, the
      National Institute for Health and Care Excellence (NICE) invited AbbVie, the
      manufacturer, to submit evidence on the use of venetoclax, within its licensed
      indication. The Evidence Review Group (ERG), Warwick Evidence, was asked to
      provide an independent and critical review of the submitted evidence. Evidence
      came from three single-arm trials in CLL patients with or without 17p deletion
      [del(17p])/TP53 chromosomal abnormalities. The anticipated licensed indication
      specified that venetoclax-eligible del(17p)/TP53 patients should have not
      responded to, or be deemed unsuitable for, B-cell receptor inhibitor (BCRi)
      therapy, and that non-del(17p)/TP53 patients should have not responded to both
      chemoimmunotherapy and BCRi therapy. The three trials were heterogeneous in terms
      of both del(17p)/TP53 status and previous exposure to BCRi therapy. The M13-982
      study investigated 158 R/R CLL patients with the 17p deletion, but only a small
      number had received previous BCRi therapy; the M12-175 study investigated 67
      patients with CLL or small lymphocytic lymphoma, some with the 17p deletion, but
      very few previously treated with BCRi therapy; and the M14-032 study included 105
      patients previously treated with BCRi therapy (either idelalisib or ibrutinib),
      some of whom had unknown mutation status. The ERG concluded that the study
      populations did not directly conform to those specified in the licensed
      indication or in the NICE scope. Outcomes reported included overall response rate
      (ORR), duration of response, progression-free survival (PFS) and overall survival
      (OS); adverse events were reported for the pooled population of all three
      studies, as well as separately for each study. The median PFS was 41.4 and 27.2
      months among patients in the M12-175 and M13-982 trials, respectively, whereas
      the median PFS was not reached in the M14-032 trial. Some results were designated
      academic in confidence and cannot be reported here. The submission provided a de
      novo partitioned survival cost-effectiveness model with three health states: pre
      progression, post-progression and dead. Transition probabilities between health
      states were estimated using Weibull models for PFS and OS. The ERG judged the
      model structure to be appropriate. Venetoclax was compared with best supportive
      care (BSC) in patients with or without del(17p)/TP53 mutation status, and with
      palliative care (PC). To populate the del(17p)/TP53 venetoclax arm, the
      submission pooled del(17p)/TP53 patients from all three studies and fitted
      Weibull models for PFS and OS. PFS and OS models for non-del(17p)/TP53 venetoclax
      patients were obtained by applying hazard ratios (HRs) to the del(17p)/TP53 OS
      and PFS models, derived using Cox's regression analysis comparing del(17p)/TP53
      and non-del(17p)/TP53 patients pooled from the M14-032 and M12-175 studies. The
      ERG expressed reservations about the company's pooling procedure, but
      acknowledged its expedience given the small evidence base. For the BSC comparator
      arm, the submission used the rituximab + placebo arm from a randomised controlled
      trial comparing idelalisib + rituximab versus placebo + rituximab ('study 116').
      Weibull regression data for OS and PFS were taken from the idelalisib STA (ID764)
      submitted by Gilead to NICE. The ERG considered the use of the study 116
      rituximab arm to be inconsistent with the licensed indication for venetoclax
      because these patients had neither not responded to nor were inappropriate for
      BCRi therapy, being eligible to be randomised to idelalisib. Another difficulty
      was the requirement for a technical correction in survival analysis because of
      considerable switching from rituximab to idelalisib. The ERG considered that post
      progression survival of patients from the idelalisib arm of study 116 provided a
      more appropriate representation of BSC since these patients had not responded to
      BCRi therapy, consistent with venetoclax's licensed indication. For PC, the
      company submission used data from the UK CLL Forum. The company's base-case
      analysis indicated that venetoclax was clinically effective, but the resulting
      incremental cost-effectiveness ratios (ICERs) for del(17p)/TP53 (L39,940/quality
      adjusted life-year [QALY] gained) and non-del(17p)/TP53 (L47,370/QALY gained)
      patients were well above the NICE threshold of L20,000-30,000/QALY. The ERG
      identified two errors in the implementation of the company's parametric models
      one related to the implementation of HRs, and the other to the derivation of the
      Weibull shape parameters obtained from the Gilead idelalisib submission. The ERG
      made plausible adjustments to the company's base-case and corrected errors,
      resulting in a reduced estimate of the cost effectiveness of venetoclax in non
      del(17p)/TP53 and del(17p)/TP53 indications; in the ERG's preferred base case,
      using post-progression survival of patients in the idelalisib arm of study 116 as
      the BSC comparator, deterministic ICERs were higher than the company's base-case
      for both indications: L57,476/QALY gained for del(17p)/TP53 and L77,779/QALY
      gained for non-del(17p)/TP53. The NICE Appraisal Committee's preliminary
      recommendation was that venetoclax used within its licensed indication should not
      be recommended for use in the National Health Service (NHS). In response to the
      preliminary recommendation, the company submitted new analyses; however, at a
      subsequent appraisal committee meeting, the original recommendation was upheld
      and the committee concluded there were large uncertainties around the clinical
      effectiveness of venetoclax and BSC, and that under the committee's preferred
      assumptions, the ICERs were higher than those generally considered cost
      effective, even when end-of-life criteria were taken into account. The company
      submitted further evidence, and the final guidance recommended venetoclax for use
      with the Cancer Drugs Fund for the two populations in this technology appraisal.

PMID- 29222671
TI  - Biological potential of thiazolidinedione derivatives of synthetic origin.
AB  - Thiazolidinediones are sulfur containing pentacyclic compounds that are widely
      found throughout nature in various forms. Thiazolidinedione nucleus is present in
      numerous biological compounds, e.g., anti-malarial, antimicrobial, anti
      mycobacterium, anticonvulsant, antiviral, anticancer, anti-inflammatory,
      antioxidant, anti-HIV (human immunodeficiency virus) and antitubercular agent.
      However, owing to the swift development of new molecules containing this nucleus,
      many research reports have been generated in a brief span of time. Therefore
      seems to be a requirement to collect recent information in order to understand
      the current status of the thiazolidinedione nucleus in medicinal chemistry
      research, focusing in particular on the numerous attempts to synthesize and
      investigate new structural prototypes with more effective antidiabetic,
      antimicrobial, antioxidant, anti-inflammatory, anticancer and antitubercular
      activity.

PMID- 29222672
TI  - Morphological alterations in the position of the mandibular foramen in dentate
      and edentate mandibles.
AB  - The technique of inferior alveolar nerve (IAN) block must be based on precise
      anatomical knowledge regarding the correct position of the mandibular foramen
      (MF). The aim of the investigation reported here was to determine the anatomic
      and topographic localization of the MF according to mandibular ramus anatomic
      landmarks and to identify morphological alterations in the position of the MF and
      size and shape of the ramus in terms of the impact of tooth socket loss in the
      molar and premolar region. Seventy-three dry human adult mandibles were divided
      into two groups according to dental status. These were measured to determine the
      distances from the anterior and posterior ramus border (AB, PB) to the midpoint
      of the MF fossa, and from the mandibular notch (MN) and inferior ramus border
      (IB) to the MF entering point. A number of relevant ramus anatomic features were
      analyzed, such as ramus width (RW), height (RH), and thickness (RT). The MF was
      closer to the PB and IB in edentate mandibles (right/left mean PB-MF 10.66 +/-
      1.84/11.06 +/- 2.05 mm; right/left mean IB-MF 21.77 +/- 3.23/21.8 +/- 2.27 mm)
      compared to dentate mandibles (right/left mean PB-MF 11.87 +/- 2.08/12.04 +/-
      1.94 mm; right/left mean IB-MF 22.94 +/- 3.09/22.74 +/- 3.74 mm). Edentate
      mandibles demonstrated reduced RW (right/left mean RW 26.03 +/- 3.53/26.49 +/-
      3.90 mm), significantly reduced (p = 0.03) right RH (right/left mean RH 43.56 +/-
      4.74/45.43 +/- 4.86 mm), and significantly reduced (p < 0.05) RT in the area of
      the MF fossa depression (right/left mean RT 5.52 +/- 1.21/5.21 +/- 0.91 mm)
      compared to dentate mandibles (right/left mean RW 27.34 +/- 3.84/27.48 +/- 3.80
      mm; right/left mean RH 46.33 +/- 4.52/47.40 +/- 4.20 mm; right/left mean RT 7.86
      +/- 1.98/8.10 +/- 1.92 mm). Alterations in MF position and mandibular ramus
      anatomic features in edentate mandibles increase the potential risk of
      complications and failure of IAN block.

PMID- 29222673
TI  - Ureteric entrapment in sacroiliac joint causing hydroureter and ipsilateral
      kidney hypertrophy.
AB  - A unilateral megaureter was found in an elderly female cadaver during routine
      dissection. The left proximal ureter, which was thick and convolute, descended
      and entered into the pelvic cavity, where the distal ureter was attached to the
      posterior pelvic wall at the inlet level. Removal of connective tissue
      surrounding the attached region revealed ureteric entrapment in the sacroiliac
      joint. The ipsilateral kidney, from which the megaureter originated, showed no
      pelvicalyceal dilatation. In contrast, the left kidney was enlarged, weighing 24%
      more than the right kidney. Differences in the upper urinary system between the
      obstructed and normal sides were examined in terms of gross anatomy,
      measurements, and histology. Although ureteric obstruction frequently causes
      hydroureter and hydronephrosis, the present case is very rare as the incomplete
      obstruction may have stimulated ipsilateral kidney growth, instead of
      contralateral compensatory augmentation.

PMID- 29222674
TI  - Effect of rehabilitation exercise durations on the dynamic bone repair process by
      coupling polymer scaffold degradation and bone formation.
AB  - Implantation of biodegradable scaffold is considered as a promising method to
      treat bone disorders, but knowledge of the dynamic bone repair process is
      extremely limited. In this study, based on the representative volume cell of a
      periodic scaffold, the influence of rehabilitation exercise duration per day on
      the bone repair was investigated by a computational framework. The framework
      coupled scaffold degradation and bone remodeling. The scaffold degradation was
      described by a function of stochastic hydrolysis independent of mechanical
      stimulation, and the bone formation was remodeled by a function of the mechanical
      stimulation, i.e., strain energy density. Then, numerical simulations were
      performed to study the dynamic bone repair process. The results showed that the
      scaffold degradation and the bone formation in the process were competitive. An
      optimal exercise duration per day emerged. All exercise durations promoted the
      bone maturation with a final Young's modulus of 1.9 +/- 0.3 GPa. The present
      study connects clinical rehabilitation and fundamental research, and is helpful
      to understand the bone repair process and further design bone scaffold for bone
      tissue engineering.

PMID- 29222675
TI  - Accuracy of computed tomography for selecting the revascularization method based
      on SYNTAX score II.
AB  - OBJECTIVES: The application of SYNTAX score II based on coronary CT angiography
      (CCTA) for selecting further treatment options has not been studied. This study
      aimed to investigate the diagnostic performance of CCTA combined with SYNTAX
      score II for selecting the revascularization method compared with invasive
      coronary angiography (ICA) based on 2014 European Society of Cardiology
      (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines.
      METHODS: From January-May 2011, 160 patients who underwent both CCTA and ICA
      within 30 interval days were included. The diagnostic performance of CCTA, CCTA
      plus CT-SYNTAX score I and CT-SYNTAX score II was analysed using ICA counterparts
      as references. RESULTS: Overall sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy of CCTA plus CT-SYNTAX I for
      selecting coronary artery bypass grafting (CABG) candidates using ICA plus ICA
      SYNTAX I as reference, were 70.6 %, 95.8 %, 66.7 %, 96.5 % and 93.1 %,
      respectively. The diagnostic performance of CCTA plus CT-SYNTAX II showed
      improvement with values of 83.3 %, 97.3 %, 71.4 %, 98.6 % and 96.3 %,
      respectively, using ICA plus ICA-SYNTAX II as reference. CONCLUSIONS: CCTA
      combined with CT-SYNTAX score II is an accurate method for selecting CABG surgery
      candidates compared with ICA-SYNTAX score II. KEY POINTS: * SYNTAX plus CCTA can
      be highly specific for selecting the revascularization method. * SYNTAX II was
      complemented by including clinical considerations to SYNTAX I. * CCTA plus CT
      SYNTAX II is an accurate method for selecting CABG candidates.

PMID- 29222676
TI  - Intravoxel incoherent motion MR imaging of early cervical carcinoma: correlation
      between imaging parameters and tumor-stroma ratio.
AB  - OBJECTIVES: To investigate if intravoxel incoherent motion (IVIM) MR imaging can
      predict the tumour-stroma ratio (TSR) in patients with early cervical carcinoma.
      METHODS: Fifty-four patients with early cervical carcinoma were prospectively
      enrolled into this study. All patients underwent IVIM imaging and parameters
      including D, D* and f value were measured. The tumours were classified into
      stroma-rich and stroma-poor group according to TSR, and comparisons of IVIM
      parameters between two groups were performed. The relationships between IVIM
      parameters and TSR were analysed by using a multivariate multi-regression
      analysis. RESULTS: D and f values were significantly lower in stroma-poor tumours
      than in stroma-rich tumours (p=0.02, 0.04), while the difference in D* value
      between two groups didn't achieve statistical significance (p=0.09). The areas
      under ROC curves of D and f values in discriminating stroma-rich and stroma-poor
      tumours were 0.835 (95%CI=0.616~0.905) and 0.686 (95%CI=0.575~0.798). In multiple
      linear regression analysis, D value, pathologic type, histologic grade, tumour
      size and f value were independently correlated with TSR of cervical carcinoma.
      CONCLUSIONS: D and f values are independently correlated with TSR of cervical
      carcinoma and have the potential for quantitative measurement of TSR. KEY POINTS:
      * TSR is a recognized independent prognostic factor in many solid tumours. * D
      and f values measured by IVIM MRI are independently correlated with TSR while D*
      is not. * IVIM offers the potential to predict TSR.

PMID- 29222677
TI  - Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging
      for prostate cancer detection in a re-biopsy population.
AB  - OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation
      transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in
      a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI
      (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with
      and without MT saturation. Patients underwent transperineal biopsy based on
      prospectively defined MRI targets. Receiver-operating characteristic (ROC)
      analyses assessed the parameters and Wilcoxon-signed ranked test assessed
      relationships between metrics. RESULTS: Twenty patients had >= 1 core positive
      for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, >= 4+3 in
      6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion
      coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio
      (MTR) significantly higher in tumour versus benign tissue (all p <= 0.005); ROC
      values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR
      compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and
      Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No
      parameter separated low-grade (Gleason 3+3) from high-grade (>= 3+4) disease for
      either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp
      and MTR all distinguished benign tissue from tumour, but none reliably
      differentiated low- from high-grade disease. KEY POINTS: * MTR was significantly
      higher in PZ and TZ tumours versus normal tissue * K app was significantly lower
      and D app higher for PZ and TZ tumours * There was no incremental value for
      DKI/MTI over mono-exponential ADC parameters * No parameter could consistently
      differentiate low-grade (Gleason 3+3) from high-grade (>= 3+4) disease *
      Divergent MTR/DKI values in TZ tumours suggests they offer different functional
      information.

PMID- 29222678
TI  - Dose-responses for mortality from cerebrovascular and heart diseases in atomic
      bomb survivors: 1950-2003.
AB  - The scientific community faces important discussions on the validity of the
      linear no-threshold (LNT) model for radiation-associated cardiovascular diseases
      at low and moderate doses. In the present study, mortalities from cerebrovascular
      diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors
      were analyzed. The analysis was performed with several radio-biologically
      motivated linear and nonlinear dose-response models. For each detrimental health
      outcome one set of models was identified that all fitted the data about equally
      well. This set was used for multi-model inference (MMI), a statistical method of
      superposing different models to allow risk estimates to be based on several
      plausible dose-response models rather than just relying on a single model of
      choice. MMI provides a more accurate determination of the dose response and a
      more comprehensive characterization of uncertainties. It was found that for CeVD,
      the dose-response curve from MMI is located below the linear no-threshold model
      at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk
      compared to the LNT model. A sublinear dose-response was also found for heart
      diseases (0-3 Gy). The analyses provide no conclusive answer to the question
      whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart
      diseases. MMI suggests that the dose-response curves for CeVD and heart diseases
      in the Lifespan Study are sublinear at low and moderate doses. This has relevance
      for radiotherapy treatment planning and for international radiation protection
      practices in general.

PMID- 29222679
TI  - [Objective audiometry and clinical application].
AB  - Subjective and objective hearing tests are used for evaluation of hearing
      impairments. Objective methods include impedance measurement with tympanometry
      and stapedius reflex measurement, otoacoustic emissions (OAE), and auditory
      evoked potentials (AEP). Combined with statistical analysis, the introduction of
      auditory steady state responses (ASSR) has enabled objective hearing tests in
      newborn hearing screening and automated hearing threshold assessment. The type
      and degree of hearing loss can be determined using the abovementioned methods.
      Precise interpretation of the test results is helpful to distinguish an auditory
      synaptopathy/neuropathy from classical sensorineural hearing loss.

PMID- 29222680
TI  - [Life and death decisions : The German Federal Court of Justice states new
      requirements for advance directives].

PMID- 29222681
TI  - [The right to one's own image : Caution required with patient photos and video
      documentation in talks, publications, and on the practice homepage].

PMID- 29222682
TI  - [Three-dimensional analysis of nasal physiology : Representation by means of
      computational fluid dynamics].
AB  - The human nose takes primary responsibility for preconditioning inhaled air.
      Numerous pathologies can affect the physiology of the nose. The beginnings of
      flow analyzes were carried out with three-dimensional casting models and
      differently colored liquids. Temperature and humidity could not be taken into
      account. Today, much more complex analyzes are possible using computational fluid
      dynamics (CFD), which are based on three-dimensional models generated from
      computed tomography (CT) or magnetic resonance imaging (MRI) datasets. Here, flow
      velocities, temperature, humidity, and pressure differences can be simulated and
      displayed in high-resolution videos as a function of multiple boundary
      conditions. The analysis of pathological changes or surgical interventions is
      thereby possible.

PMID- 29222683
TI  - Evaluation of urban transformation areas in terms of user satisfaction: the case
      study of Zagnos Valley (Trabzon/Turkey).
AB  - Following the Industrial Revolution, rapid urbanization brought about many socio
      economic, physical, and cultural problems. The concept of urban transformation
      has come to the fore as a solution to these emerging troubles. Especially since
      1980, in Turkey, like other developing countries, the concept of urban
      transformation has only been evaluated as an economic standpoint ignoring the
      social and spatial dimensions of that area and the quality of life of people
      residing in the area. Therefore, the necessity of these socially accessible areas
      where individuals can regenerate themselves in spiritual and physical terms has
      increased even more. However, when the urban transformation projects are put into
      practice, the needs and demands of the users are not taken into account;
      moreover, there are no studies showing the satisfaction or dissatisfaction of the
      users following the implementation. In the current study,
      satisfaction/dissatisfaction levels of the users were determined by asserting the
      user profile of Zagnos Valley, which is the first urban transformation area of
      Trabzon. In the valley, which is an important air corridor and a recreation area
      for Trabzon, questionnaires were implemented through face-to-face interview
      technique. Factor analysis was carried out in order to reveal the socio
      demographic characteristics, space usage trends, and spatial usage
      characteristics of the users. In order to measure satisfaction and
      dissatisfaction levels, the determined criteria were weighted on a 5-point Likert
      scale and frequency distributions were examined. In this way, solution proposals
      have been made in order to increase the level of satisfaction and remediate the
      level of dissatisfaction of users.

PMID- 29222684
TI  - How much do plastic surgeons add to the closure of myelomeningoceles?
AB  - PURPOSE: This study reviews the outcomes of children undergoing myelomeningocele
      (MMC) repair in the paediatric neurosurgical department in Cardiff. These
      procedures are historically performed by paediatric neurosurgeons with occasional
      support from plastic surgeons for the larger lesions. We reviewed the
      postoperative outcomes over a 9-year period to assess the efficacy of having a
      plastic surgeon present at all MMC closures. METHODS: Analysis of a prospectively
      collected database of all MMC closures performed at University Hospital Wales
      from April 2009 to August 2017 was used. Comparison was made with the published
      literature especially with regard to complications. RESULTS: Thirty-one children,
      13 males and 18 females, underwent MMC closure over the 9-year period. Twenty
      four (77.4%) defects were closed by direct approximation. Seven patients (22.5%)
      required a more complex plastic procedure to obtain closure. Two patients (6.5%)
      had a wound complication, one wound infection and one flap edge necrosis both
      healing with dressings alone. Two patients had cerebrospinal fluid (CSF) leaks
      that responded to ventriculo-peritoneal shunting. Two patients died from
      unrelated conditions during the study period. CONCLUSION: In our series, 7/31
      (22.5%) cases involved a more complex closure in keeping with the literature. The
      authors feel that having the plastic surgeon at all closures has led to a low
      wound complication rate.

PMID- 29222685
TI  - Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in
      locally advanced cervical cancer treated with chemoradiotherapy.
AB  - PURPOSE: The aim of this study is to determine if radiomics features from
      18fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) and magnetic resonance imaging (MRI) images could contribute to
      prognoses in cervical cancer. METHODS: One hundred and two patients (69 for
      training and 33 for testing) with locally advanced cervical cancer (LACC)
      receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this
      study. 18F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted
      imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes
      were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET
      images and with 3D SlicerTM in the MRI images. Radiomics features (intensity,
      shape, and texture) were extracted and their prognostic value was compared with
      clinical parameters for recurrence-free and locoregional control. RESULTS: In the
      training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and
      relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs.
      III-IV) and metabolic response (complete vs. non-complete) were probably
      associated with outcome without reaching statistical significance, contrary to
      several radiomics features from both PET and MRI sequences. Multivariate analysis
      in training test identified Grey Level Non UniformityGLRLM in PET and EntropyGLCM
      in ADC maps from DWI MRI as independent prognostic factors. These had
      significantly higher prognostic power than clinical parameters, as evaluated in
      the testing cohort with accuracy of 94% for predicting recurrence and 100% for
      predicting lack of loco-regional control (versus ~50-60% for clinical
      parameters). CONCLUSIONS: In LACC treated with CRT, radiomics features such as
      EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively,
      are independent predictors of recurrence and loco-regional control with
      significantly higher prognostic power than usual clinical parameters. Further
      research is warranted for their validation, which may justify more aggressive
      treatment in patients identified with high probability of recurrence.

PMID- 29222687
TI  - Chrysophyllum cainito (apple-star): a fruit with gastroprotective activity in
      experimental ulcer models.
AB  - The gastroprotective potential of the methanolic extracts from peels (MEPe),
      seeds (MESe) and pulp (MEPu) of Chrysophyllum cainito L. (Sapotaceae) fruits was
      evaluated in mice using ethanol/HCl- and indomethacin-induced ulcer, as well as
      the antiulcer effect of the juice and flour from this fruit. The lowest oral
      gastroprotective dose of MEPe, MESe and MEPu against ethanol/HCl was 3, 3 and 10
      mg/kg, respectively. Moreover, all extracts increased mucin secretion at 176, 198
      and 193%. Intraperitoneal administration of MEPe (0.3 mg/kg), MESe (0.3 mg/kg)
      and MEPu (1 mg/kg) also promoted gastroprotection against ethanol/HCl. In
      addition, MEPe (3 mg/kg, p.o), MESe (3 mg/kg, p.o) and MEPu (10 mg/kg, p.o)
      reduced indomethacin-induced gastric ulcer in mice by 78, 70 and 50%,
      respectively. Regarding the mode of action, the gastroprotective effect of MEPe
      was decreased by the pre-administration of N-ethylmaleimide (NEM, a sulfhydryl
      group chelator, 10 mg/kg, i.p), glibenclamide (a potassium channel blocker, 10
      mg/kg, i.p), yohimbine (10 mg/kg, i.p, an alpha-adrenergic receptor antagonist,
      10 mg/kg, i.p) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p). The
      gastroprotective effect of MESe was reduced by the pre-administration of NEM,
      glibenclamide, N-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase
      inhibitor, 70 mg/kg, i.p) and yohimbine, while MEPu had the gastroprotective
      effect decreased in animals pretreated with NEM and L-NAME. However, the extracts
      did not reduce gastric acid secretion. The supplementation with the flour from C.
      cainito fruit at 10% by 7 days, but not the juice intake, displayed
      gastroprotective potential, evidencing the fruit as a promising functional food.
      Together, the antiulcer effect of extracts of the C. cainito fruit in different
      experimental models was confirmed by the favoring of mucosal protective
      mechanisms among different, but complementary, modes of action. In parallel, the
      gastroprotective effects of the flour from C. cainito fruit were also described.

PMID- 29222686
TI  - EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine
      System Genes.
AB  - Cognitive or executive control is a critical mental ability, an important marker
      of mental illness, and among the most heritable of neurocognitive traits. Two
      candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a
      roles in the regulation of cortical dopamine, have been consistently associated
      with cognitive control. Here, we predicted that individuals with the COMT Met/Met
      allele would show improved response execution and inhibition as indexed by event
      related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat
      allele would show impaired brain activity. We used independent component analysis
      (ICA) to separate brain source processes contributing to high-density EEG scalp
      signals recorded during the task. As expected, individuals with the DRD4 7-repeat
      polymorphism had reduced parietal P3 source and scalp responses to response (Go)
      compared to those without the 7-repeat. Contrary to our expectation, the COMT
      homozygous Met allele was associated with a smaller frontal P3 source and scalp
      response to response-inhibition (NoGo) stimuli, suggesting that while more
      dopamine in frontal cortical areas has advantages in some tasks, it may also
      compromise response inhibition function. An interaction effect emerged for P3
      source responses to Go stimuli. These were reduced in those with both the 7
      repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous
      polymorphisms but not in those with the heterozygous Val/Met polymorphism. This
      epistatic interaction between DRD4 and COMT replicates findings that too little
      or too much dopamine impairs cognitive control. The anatomic and functional
      separated maximally independent cortical EEG sources proved more informative than
      scalp channel measures for genetic studies of brain function and thus better
      elucidate the complex mechanisms in psychiatric illness.

PMID- 29222688
TI  - Comparison of qualitative and quantitative CT and MRI parameters for monitoring
      of longitudinal spine involvement in patients with multiple myeloma.
AB  - PURPOSE: To compare qualitative and quantitative computed tomography (CT) and
      magnetic resonance imaging (MRI) parameters for longitudinal disease monitoring
      of multiple myeloma (MM) of the axial skeleton. MATERIALS AND METHODS: We
      included 31 consecutive patients (17 m; mean age 59.20 +/- 8.08 years) with MM,
      who underwent all baseline (n = 31) and at least one or more (n = 47) follow-up
      examinations consisting of multi-parametric non-enhanced whole-body MRI (WBMRI)
      and non-enhanced whole-body reduced-dose thin-section MDCT (NEWBMDCT) between
      06/2013 and 09/2016. We classified response according to qualitative CT criteria
      into progression (PD), stable(SD), partial/very good partial (PR/VGPR) and
      complete response(CR), grouping the latter three together for statistical
      analysis because CT cannot reliably assess PR and CR. Qualitative MR-response
      criteria were defined and grouped similarly to CT using longitudinal
      quantification of signal-intensity changes on T1w/STIR/ T2*w and calculating ADC
      values. Standard of reference was the hematological laboratory (M-gradient).
      RESULTS: Hematological response categories were CR (14/47, 29.7%), PR (2/47,
      4.2%), SD (16/47, 34.0%) and PD (15/47, 29.9%). Qualitative-CT-evaluation showed
      PD in 12/47 (25.5%) and SD/PR/VGPR/CR in 35/47 (74.5%) cases. These results were
      confirmed by quantitative-CT in all focal lytic lesions (p < 0.001). Quantitative
      CT at sites with diffuse bone involvement showed significant increase of maximum
      bone attenuation (p < 0.001*) and significant decrease of minimal bone (p <
      0.002*) in the SD/PR/VGPR/CR group. Qualitative MRI showed PD in 14/47 (29.7%)
      and SD/PR/VGPR/CR in 33/47 (70.3%). Quantitative MRI diagnosis showed a
      statistically significant decrease in signal intensity on short tau inversion
      recovery sequences (STIR) in bone marrow in patients with diffuse bone marrow
      involvement achieving SD/PR/VGPR/CR (p < 0.001*). CONCLUSION: Imaging response
      monitoring using MRI is superior to CT only if qualitative parameters are used,
      whereas there was no definite benefit from using quantitative parameters with
      either CT or MRI.

PMID- 29222689
TI  - Long-Term Quantitative Evaluation of Muscle and Bone Wasting Induced by Botulinum
      Toxin in Mice Using Microcomputed Tomography.
AB  - Muscle and bone masses are highly correlated and muscles impose large loads on
      bone. Muscle wasting that accompanies bone loss has been poorly investigated. 21
      female mice were spread into seven groups. At day 0, 18 mice received Botulinum
      toxin (BTX) injection in the quadriceps muscle to induce paralysis of the right
      hind limb; the left contralateral side was used as control. Mice were sacrificed
      at 7, 14, 21, 28, 56 and 90 days post-injection. A remaining group was sacrificed
      at day 0. Trabecular bone volume was determined by microcomputed tomography
      (microCT) at the distal femur and tibia proximal metaphyses on both sides. Limbs
      were immersed in an HgCl2 solution allowing muscle visualization by microCT. On
      2D sections, the cross-sectional areas and form-factors were measured for the
      quadriceps at mid-thigh and gastrocnemius at mid-leg and these muscles were
      dissected and weighed. Bone volume decreased in the paralysed side. Bone loss was
      maximal at 56 days followed by recuperation at 90 days. The cross-sectional areas
      of gastrocnemius and quadriceps were significantly lower in the paralysed limb
      from 7 days; the decrease was maximum at 21 days for the gastrocnemius and 28
      days for the quadriceps. No difference in form-factors was found between the two
      limbs. Similar results were obtained with the anatomical method and significant
      correlations were obtained between the two methods. Quantitative analysis of
      muscle loss and recovery was possible by microCT after using a metallic contrast
      agent. Loss of bone secondary to muscle wastage induced by BTX and recovery
      showed a parallel evolution for bone and muscles.

PMID- 29222690
TI  - Risk factor of contralateral radiculopathy following microendoscopy-assisted
      minimally invasive transforaminal lumbar interbody fusion.
AB  - PURPOSE: Microendoscopy-assisted minimally invasive transforaminal lumbar
      interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar
      degenerative disease; however, some patients show contralateral radiculopathy
      postoperatively. This study aims to investigate its risk factor. METHODS: A total
      of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were
      divided into symptomatic and asymptomatic groups according to the presence of
      postoperative contralateral radiculopathy. Both preoperative and postoperative
      radiographic parameters, as well as their changes were compared between the two
      groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc
      height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA).
      Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or
      bilateral canal decompression through unilateral route) were also analyzed as
      potential risk factors. Receiver operating characteristic (ROC) curve was drawn
      for the risk factor to determine the optimal threshold for predicting
      postoperative contralateral radiculopathy. Besides, clinical outcome assessment,
      involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics
      Association Score (JOA) and Oswestry Disability Index (ODI), was also compared
      between the two groups before surgery and at final follow-up (at least 3 months
      after the surgery for asymptomatic patients or final treatments of contralateral
      radiculopathy for symptomatic cases). RESULTS: Postoperative contralateral
      radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and
      postoperative CFA as well as its change were significantly decreased in
      symptomatic group compared with asymptomatic group (all P < 0.05). For the
      remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative
      and change values showed no statistical difference between the two groups (all P
      > 0.05). Neither screw breach nor decompression method revealed statistical
      association with this complication (both P > 0.05). Based on ROC curve, the
      optimal threshold of preoperative CFA was 0.76 cm2. At final follow-up,
      significant improvement in VAS (back and leg), JOA and ODI was observed in both
      groups compared with preoperative baseline (all P < 0.05), while no difference
      was found between the two groups (all P > 0.05). CONCLUSIONS: Preoperative
      contralateral foramen stenosis is the risk factor of contralateral radiculopathy
      following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is
      not larger than 0.76 cm2, prophylactic measures, including both indirect and
      direct decompression of contralateral foramen, are recommended.

PMID- 29222691
TI  - A rare cause of tricuspid regurgitation.

PMID- 29222692
TI  - Advances in understanding hilar mossy cells of the dentate gyrus.
AB  - Hilar mossy cells (MCs) of the dentate gyrus (DG) distinguish the DG from other
      hippocampal subfields (CA1-3) because there are two glutamatergic cell types in
      the DG rather than one. Thus, in the DG, the main cell types include
      glutamatergic granule cells (GCs) and MCs, whereas in CA1-3, the only
      glutamatergic cell type is the pyramidal cell. In contrast to GCs, MCs are
      different in morphology, intrinsic electrophysiological properties, afferent
      input and axonal projections, so their function is likely to be very different
      from GCs. Why are MCs necessary to the DG? In past studies, the answer has been
      unclear because MCs not only excite GCs directly but also inhibit them
      disynaptically, by exciting GABAergic neurons that project to GCs. Results of new
      studies are discussed that shed light on this issue. These studies take advantage
      of recently available transgenic mice with Cre recombinase expression mostly in
      MCs and techniques such as optogenetics and DREADDs (designer receptors
      exclusively activated by designer drugs). The recent studies also address in vivo
      behavioral functions of MCs. Some of the results support past hypotheses whereas
      others suggest new conceptualizations of how the MCs contribute to DG circuitry
      and function. While substantial progess has been made, additional research is
      still needed to clarify the characteristics and functions of these unique cells.

PMID- 29222694
TI  - Preparation and evaluation of decellularized porcine carotid arteries cross
      linked by genipin: the preliminary results.
AB  - Decellularized arteries have been considered as promising scaffolds for small
      diameter vascular substitutes. However, weakened mechanical properties,
      immunological rejection and rapid degradation after transplantation still exist
      after decellularization. Previous studies indicated that genipin cross-linking
      can solve these problems. Therefore, genipin was selected as the cross-linking
      agent for the pre-treatment of decellularized arteries in our study. Histological
      analysis, scanning electron microscopy, mechanical properties analysis and
      subcutaneous embedding experiment were adopted to investigate the efficiency of
      decellularization and the effect of genipin cross-linking on improving
      mechanical, structural and biological properties of decellularized arteries.
      Decellularization protocols based on three trypsin concentrations were used to
      prepare decellularized arteries, after decellularization, arteries were cross
      linked with genipin. Results showed that 0.5% trypsin was the most efficient
      concentration to remove cellular components and preserve ECM. However, mechanical
      properties of 0.5% trypsin decellularized arteries weakened significantly, while
      genipin cross-linking improved mechanical properties of decellularized arteries
      to the same level as fresh arteries. After 4 weeks subcutaneous embedding, cross
      linked arteries caused the mildest inflammatory response. In conclusion, genipin
      could be employed as an ideal cross-linking agent to strengthen mechanical
      properties, enhance the resistance to degradation and reduce the antigenicity of
      decellularized arteries for small-diameter blood vessel tissue engineering
      applications.

PMID- 29222695
TI  - The effects of enhanced attention and working memory on smooth pursuit eye
      movement.
AB  - It has long been suggested that increasing attentional demands can alter smooth
      pursuit eye movements, but the precise nature of the changes generated is not
      clear. Our goal was to examine smooth pursuit with a task that enhanced attention
      to the target and that increased demands on working memory, without distracting
      from the target. 15 subjects tracked a target moving around a predictable
      circular trajectory at a constant tangential velocity. An n-back task with two
      levels of additional working memory load was integrated into the pursuit target
      to increase cognitive demands. In the single-task conditions, subjects either
      performed pursuit alone or the n-back task with a stationary target. In the dual
      task conditions, pursuit and the n-back task were performed together. Performance
      of the n-back tasks was not impaired by simultaneous smooth pursuit. The n-back
      tasks had negligible effects on horizontal or vertical pursuit gain, but
      generated increased phase lag and reduced the variability of position error
      during pursuit. Increasing the difficulty of the n-back task further reduced the
      variability of position errors. We conclude that enhanced attention does not
      alter the velocity gain of smooth pursuit but rather improves its consistency. As
      long as attention remains focused on the target, increased attentional demands
      further reduce pursuit variability. Increases in phase lag may serve to improve
      attentional processing of the target.

PMID- 29222693
TI  - Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.
AB  - Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural
      crest tissues of the sympathetic nervous system. NB is highly heterogeneous both
      from a clinical and a molecular perspective. Clinically, this cancer represents a
      wide range of phenotypes ranging from spontaneous regression of 4S disease to
      unremitting treatment-refractory progression and death of high-risk metastatic
      disease. At a cellular level, the heterogeneous behavior of NB likely arises from
      an arrest and deregulation of normal neural crest development. In the present
      review, we summarize our current knowledge of neural crest development as it
      relates to pathways promoting 'stemness' and how deregulation may contribute to
      the development of tumor-initiating CSCs. There is an emerging consensus that
      such tumor subpopulations contribute to the evolution of drug resistance,
      metastasis and relapse in other equally aggressive malignancies. As relapsed,
      refractory disease remains the primary cause of death for neuroblastoma, the
      identification and targeting of CSCs or other primary drivers of tumor
      progression remains a critical, clinically significant goal for neuroblastoma. We
      will critically review recent and past evidence in the literature supporting the
      concept of CSCs as drivers of neuroblastoma pathogenesis.

PMID- 29222696
TI  - Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces
      NETosis and prevents septic shock-induced coagulopathy in rats.
AB  - BACKGROUND: Septic shock-induced disseminated intravascular coagulation is
      responsible for increased occurrence of multiple organ dysfunction and mortality.
      Immunothrombosis-induced coagulopathy may contribute to hypercoagulability. We
      aimed at determining whether recombinant human thrombomodulin (rhTM) could
      control exaggerated immunothrombosis by studying procoagulant responses,
      fibrinolysis activity borne by microvesicles (MVs) and NETosis in septic shock.
      METHODS: In a septic shock model after a cecal ligation and puncture-induced
      peritonitis (H0), rats were treated with rhTM or a placebo at H18, resuscitated
      and monitored during 4 h. At H22, blood was sampled to perform coagulation tests,
      to characterize MVs and to detect neutrophils extracellular traps (NETs). Lungs
      were stained with hematoxylin-eosin for inflammatory injury assessment. RESULTS:
      Coagulopathy was attenuated in rhTM-treated septic rats compared to placebo
      treated rats, as attested by a significant decrease in procoagulant annexin A5+
      MVs and plasma procoagulant activity of phospholipids and by a significant
      increase in antithrombin levels (84 +/- 8 vs. 64 +/- 6%, p < 0.05), platelet
      count (582 +/- 157 vs. 319 +/- 91 * 109/L, p < 0.05) and fibrinolysis activity
      borne by MVs (2.9 +/- 0.26 vs. 0.48 +/- 0.29 U/mL urokinase, p < 0.05). Lung
      histological injury score showed significantly less leukocyte infiltration.
      Decreased procoagulant activity and lung injury were concomitant with decreased
      leukocyte activation as attested by plasma leukocyte-derived MVs and NETosis
      reduction after rhTM treatment (neutrophil elastase/DNA: 93 +/- 33 vs. 227 +/- 48
      and citrullinated histones H3/DNA: 96 +/- 16 vs. 242 +/- 180, mOD for 109
      neutrophils/L, p < 0.05). CONCLUSION: Thrombomodulin limits procoagulant
      responses and NETosis and at least partly restores hemostasis control during
      immunothrombosis. Neutrophils might thus stand as a promising therapeutic target
      in septic shock-induced coagulopathy.

PMID- 29222697
TI  - Clinical implications of rapid ePlex(r) Respiratory Pathogen Panel testing
      compared to laboratory-developed real-time PCR.
AB  - Rapid diagnosis of respiratory infections is of great importance for adequate
      isolation and treatment. Due to the batch-wise testing, laboratory-developed real
      time polymerase chain reaction (PCR) assays (LDT) often result in a time to
      result of one day. Here, LDT was compared with rapid ePlex(r) Respiratory
      Pathogen (RP) Panel testing of GenMark Diagnostics (Carlsbad, CA, USA) with
      regard to time to result, installed isolation precautions, and
      antibacterial/antiviral treatment. Between January and March 2017, 68 specimens
      of 64 patients suspected of an acute respiratory infection were tested with LDT
      and the ePlex(r) RP panel. The time to result was calculated as the time between
      sample reception and result reporting. Information regarding isolation and
      antibacterial/antiviral treatment was obtained from the patient records. Thirty
      specimens tested LDT positive (47%) and 29 ePlex(r) RP panel positive (45%). The
      median time to result was 27.1 h (range 6.5-96.6) for LDT versus 3.4 h (range 1.5
      23.6) for the RP panel, p-value < 0.001. In 14 out of 30 patients, isolation was
      discontinued based on the ePlex(r) RP panel results, saving 21 isolation days.
      ePlex(r) RP panel test results were available approximately one day ahead of the
      LDT results in the 19 patients receiving antiviral/antibacterial treatment. In
      addition, two bacterial pathogens, not requested by the physician, were detected
      using the RP panel. Analysis of respiratory infections with the ePlex(r) RP panel
      resulted in a significant decrease in time to result, enabling a reduction in
      isolation days in half of the patients. Furthermore, syndromic RP panel testing
      increased the identification of causative pathogens.

PMID- 29222698
TI  - Efficacy evaluation of iclaprim in a neutropenic rat lung infection model with
      methicillin-resistant Staphylococcus aureus entrapped in alginate microspheres.
AB  - The objective of this study was to demonstrate the efficacy of iclaprim in a
      neutropenic rat lung infection model with methicillin-resistant Staphylococcus
      aureus (MRSA) entrapped in alginate beads. An inoculum of 5.25 * 105 colony
      forming units (CFU)/mL of S. aureus strain AH1252 was administered
      intratracheally to rats with prepared alginate bacteria suspensions. Beginning 2
      h post-infection, rats received: (1) iclaprim 80 mg/kg (n = 16); (2) iclaprim 60
      mg/kg (n = 16), or (3) vancomycin 50 mg/kg (n = 24), for 3 days via subcutaneous
      (SC) injection every 12 h. Twelve hours after the last treatment, rats were
      euthanized and lungs collected for CFU determination. Iclaprim administered at 80
      mg/kg or 60 mg/kg or vancomycin 50 mg/kg SC twice a day for 3 days resulted in a
      6.05 log10 CFU reduction (iclaprim 80 mg/kg compared with control, p < 0.0001),
      5.11 log10 CFU reduction (iclaprim 60 mg/kg compared with control, p < 0.0001),
      and 3.42 log10 CFU reduction, respectively, from the controls (p < 0.0001).
      Iclaprim 80 mg/kg and 60 mg/kg resulted in 2.59 and 1.69 log10 CFU reductions,
      respectively, from vancomycin-treated animals (80 mg/kg iclaprim vs. vancomycin,
      p = 0.0005; 60 mg/kg iclaprim vs. vancomycin, p = 0.07). Animals receiving
      iclaprim, vancomycin, and controls demonstrated 100%, 91.7%, and 48.3% survival,
      respectively. In this neutropenic rat S. aureus lung infection model, rats
      receiving iclaprim demonstrated a greater CFU reduction than the controls or
      those receiving vancomycin.

PMID- 29222699
TI  - Dabigatran level monitoring prior to idarucizumab administration in patients
      requiring emergent cardiac surgery.

PMID- 29222700
TI  - Perspectives from the Patient and the Healthcare Professional in Multiple
      Sclerosis: Social Media and Participatory Medicine.
AB  - When faced with a diagnosis of multiple sclerosis (MS), patients often turn to
      the Internet and social media to find support groups, read about the experiences
      of other people affected by MS and seek their advice, and research their
      condition and treatment options to discuss with their healthcare professionals
      (HCPs). Here, we examine the use of social media and the Internet among patients
      with MS, considering its impact on patient empowerment and patient participation
      in treatment decision-making and MS research. These themes are exemplified with
      first-hand experiences of the patient author. We also explore the impact of the
      Internet and social media on the management of patients from the perspective of
      HCPs, including new opportunities for HCPs to engage in participatory medicine
      and to improve communication with and among patients. We consider both the
      benefits afforded to and the potential pitfalls faced by HCPs when interacting
      with their patients via these routes, and discuss potential concerns around
      privacy and confidentiality in the use of the Internet and social media in the
      clinical context. Communication online is driving the evolution of the patient
      HCP relationship, and is empowering patients to participate more actively in the
      decision-making process relating to the provision of their health care. Funding
      Novartis Pharmaceuticals Corporation.

PMID- 29222701
TI  - SNF5 as a prognostic factor in skull base chordoma.
AB  - The current study aimed to characterize SNF5 expression and investigate the
      relationship between SNF5 and clinicopathological features in skull base
      chordoma. 48 patients diagnosed with skull base chordoma were enrolled in this
      study. Tissue microarray and immunohistochemistry were performed to evaluate the
      expression of SNF5 in skull base chordoma. Kaplan-Meier survival analysis was
      used to assess survival. Multivariable Cox regression analysis was used to
      identify risk factors affecting patient survival. The H-scores for cytoplasmic
      SNF5 ranged from 124.47 to 254.52. Low expression of SNF5 was correlated with
      shorter overall survival (OS) (p = 0.021). Patients with age > 55 years old had
      shorter progression free survival (PFS) and OS times than patients whose age <=
      55 years old (p = 0.005 and 0.003, respectively). The gross total resection group
      showed longer PFS than the non-gross total resection group (p = 0.024). Females
      showed shorter PFS times than males (p = 0.033). Multivariable Cox regression
      analysis showed that age, extent of resection and sex were independent prognostic
      factors for PFS (p = 0.010, 0.013 and 0.042, respectively). Age was an
      independent prognostic factor for OS (p = 0.010). Our study indicate that low
      expression of SNF5 is associated with poor prognosis in skull base chordoma.

PMID- 29222702
TI  - Molecular insights into the non-recombining nature of the spinach male
      determining region.
AB  - Spinach (Spinacia oleracea L.) is a dioecious plant with male heterogametic sex
      determination and homomorphic sex chromosomes (XY). The dioecism is utilized for
      producing commercial hybrid seeds, and hence understanding the molecular-genetic
      basis of the species' sex determining locus is an important issue for spinach
      breeding. In this study, seven dominant DNA markers were shown to completely co
      segregate with the male-determining gene in segregating spinach populations
      comprising > 1500 plants. In addition, these seven dominant DNA markers were
      completely associated with the male-determining gene in over 100 spinach
      germplasm accessions and cultivars. These observations suggest that, in spinach,
      a Y-chromosomal region around the male-determining locus does not (or almost not)
      recombine with a counterpart region on the X chromosome. Using five of the seven
      DNA markers, five bacterial artificial chromosome (BAC) clone contigs with a
      total length of approximately 690 kbp were constructed. Full sequencing of six
      representative BAC clones (total insert length 504 kbp) from the five contigs and
      a transcriptome analysis by RNA-seq revealed that the Y-chromosomal region around
      the male-determining locus contains large amounts of repetitive elements,
      suggesting that the region might be poor in gene content. Most of the repeats
      found in this region are novel Ty1-copia-like and its derivative elements that
      accumulate predominantly in heterochromatic regions. Our findings may provide
      valuable insight into spinach genome structure and clues for future research into
      the evolution of the sex determining locus.

PMID- 29222703
TI  - Relationship between self-reported cognitive function and work-related outcomes
      in breast cancer survivors.
AB  - PURPOSE: This study examined the relationship between perceived cognitive
      function including perceived cognitive impairment (PCI) and perceived cognitive
      ability (PCA) and work ability, work performance, work productivity, and
      intention to leave employment in breast cancer survivors (BCS). METHODS: A cross
      sectional study design was used in the study. Employed BCS completed
      questionnaires assessing PCI and PCA (Functional Assessment of Cancer Therapy
      Cognitive-3); emotional work demands (Self-Focused Emotional Labor Scale); and
      work ability index (WAI), work performance, work productivity (Work Limitations
      Questionnaire (WLQ), and intention to turnover. Separate regression models
      examined the relationship between PCI and PCA and work-related outcomes. RESULTS:
      Participants were 68 employed female BCS who were on average 52 (SD = 8.6) years
      old and 5 (SD = 3.8) years post-treatment with majority working full time. PCI
      was associated with poorer work ability (B = - 0.658), work performance (time-B =
      0.647, physical-B = - 0.414, and mental-B = 0.689), and work productivity (B =
      0.731), but not intent to leave work. PCA was related to higher levels of work
      ability (B = 0.472), work performance (time-B = - 0.462 and mental-B = - 0.453),
      and work productivity (beta = - 0.494), but not physical demands or intent to
      turnover. CONCLUSIONS: Employed BCS with negative perceptions of cognitive
      function reported poorer work outcomes with the exception of the intent to leave
      employment. In contrast, positive views of one's cognitive abilities were related
      to improved ratings of work outcomes again with the exception of intent to leave
      employment. IMPLICATIONS FOR CANCER SURVIVORS: Healthcare providers need to
      assess and address perceived cognitive functioning to promote work-related
      outcomes in BCS.

PMID- 29222704
TI  - Healthcare system barriers to long-term follow-up for adult survivors of
      childhood cancer in British Columbia, Canada: a qualitative study.
AB  - PURPOSE: Risk-stratified life-long follow-up care is recommended for adult
      childhood cancer survivors (CCS) to ensure appropriate prevention, screening, and
      management of late effects. The identification of barriers to long-term follow-up
      (LTFU), particularly in varying healthcare service contexts, is essential to
      develop and refine services that are responsive to survivor needs. We aimed to
      explore CCS and healthcare professionals (HCP) perspectives of healthcare system
      factors that function as barriers to LTFU in British Columbia, Canada. METHODS:
      We analyzed data from 43 in-depth interviews, 30 with CCS and 13 with HCP, using
      qualitative thematic analysis and constant comparative methods. RESULTS: Barriers
      to accessible, comprehensive, quality LTFU were associated with the following:
      (1) the difficult and abrupt transition from pediatric to adult health services,
      (2) inconvenient and under-resourced health services, (3) shifting patient-HCP
      relationships, (4) family doctor inadequate experience with late effects
      management, and (5) overdue and insufficient late effects communication with CCS.
      CONCLUSIONS: Structural, informational, and interpersonal/relational healthcare
      system factors often prevent CCS from initially accessing LTFU after discharge
      from pediatric oncology programs as well as adversely affecting engagement in
      ongoing screening, surveillance, and management of late effects. IMPLICATIONS FOR
      CANCER SURVIVORS: Understanding the issues faced by adult CCS will provide
      insight necessary to developing patient-centered healthcare solutions that are
      key to accessible, acceptable, appropriate, and effective healthcare.

PMID- 29222705
TI  - Tai Chi and Qigong for cancer-related symptoms and quality of life: a systematic
      review and meta-analysis.
AB  - PURPOSE: This study aims to summarize and critically evaluate the effects of Tai
      Chi and Qigong (TCQ) mind-body exercises on symptoms and quality of life (QOL) in
      cancer survivors. METHODS: A systematic search in four electronic databases
      targeted randomized and non-randomized clinical studies evaluating TCQ for
      fatigue, sleep difficulty, depression, pain, and QOL in cancer patients,
      published through August 2016. Meta-analysis was used to estimate effect sizes
      (ES, Hedges' g) and publication bias for randomized controlled trials (RCTs).
      Methodological bias in RCTs was assessed. RESULTS: Our search identified 22
      studies, including 15 RCTs that evaluated 1283 participants in total, 75% women.
      RCTs evaluated breast (n = 7), prostate (n = 2), lymphoma (n = 1), lung (n = 1),
      or combined (n = 4) cancers. RCT comparison groups included active intervention
      (n = 7), usual care (n = 5), or both (n = 3). Duration of TCQ training ranged
      from 3 to 12 weeks. Methodological bias was low in 12 studies and high in 3
      studies. TCQ was associated with significant improvement in fatigue (ES = - 0.53,
      p < 0.001), sleep difficulty (ES = - 0.49, p = 0.018), depression (ES = - 0.27, p
      = 0.001), and overall QOL (ES = 0.33, p = 0.004); a statistically non-significant
      trend was observed for pain (ES = - 0.38, p = 0.136). Random effects models were
      used for meta-analysis based on Q test and I 2 criteria. Funnel plots suggest
      some degree of publication bias. Findings in non-randomized studies largely
      paralleled meta-analysis results. CONCLUSIONS: Larger and methodologically sound
      trials with longer follow-up periods and appropriate comparison groups are needed
      before definitive conclusions can be drawn, and cancer- and symptom-specific
      recommendations can be made. IMPLICATIONS FOR CANCER SURVIVORS: TCQ shows promise
      in addressing cancer-related symptoms and QOL in cancer survivors.

PMID- 29222706
TI  - Acute Toxicity of Fresh and Aged Residues of Pesticides to the Parasitoid
      Tamarixia radiata and to the HLB-Bacteria Vector Diaphorina citri.
AB  - One method for controlling the Asian citrus psyllid (ACP) Diaphorina citri
      Kuwayama, the vector of the putative causal agent of Huanglongbing, uses the
      parasitoid Tamarixia radiata (Waterston). However, the general intensive use of
      insecticides has reduced the numbers of this parasitoid. This study evaluated the
      effect of the residual action of 24 insecticides on T. radiata and also
      determined the differential toxicity of insecticides to D. citri and T. radiata,
      using three bioassays. In the first, when adults of the parasitoid were exposed
      to residues of the 24 insecticides, ten were considered short-life (class 1), six
      slightly persistent (class 2), five moderately persistent (class 3), and three
      insecticides were considered persistent (class 4), under the IOBC/WPRS
      classification system. The second bioassay evaluated the sublethal concentrations
      of the persistent insecticides (formetanate, dimethoate, spinosad). Increasing
      the concentrations of the insecticides increased the number that were classified
      as persistent. In the third bioassay, evaluation of the differential toxicity of
      eight insecticides to the ACP and the parasitoid showed that chlorpyrifos and
      bifenthrin were more harmful to T. radiata. Therefore, these two insecticides are
      not recommended for application at the time of parasitoid release. Cypermethrin,
      imidacloprid, and dimethoate caused higher mortality of D. citri and are most
      often recommended in IPM programs. The choice of an insecticide for the control
      of citrus pests must be made with care, aiming to preserve the natural enemies in
      the ecosystem, and thereby contribute to the success of biological control.

PMID- 29222708
TI  - Correction to: Effect of renal transplantation on cognitive function in
      hemodialysis patients: a longitudinal study.
AB  - In the original publication, the second author's affiliation was incorrectly
      published as "Department of Physiology, RAK College of Medical Sciences, Ras Al
      Khaimah, UAE". The correct affiliation should read as "Visiting Academic, Basic
      Medical Sciences Department, College of Medicine, University of Sharjah (UAE)".

PMID- 29222707
TI  - Quantitative 3D scintigraphy shows increased muscular uptake of pyrophosphate in
      idiopathic inflammatory myopathy.
AB  - BACKGROUND: Nuclear imaging is increasingly being used in the diagnostic work-up
      of idiopathic inflammatory myopathy (IIM). Increased muscular uptake of
      technetium-99m-pyrophosphate (99mTc-PYP) has hitherto been assessed qualitatively
      by planar scintigraphy. We set out to perform quantitative tomographic
      scintigraphy in IIM. RESULTS: Ninety IIM patients and 48 control subjects
      underwent 99mTc-PYP single-photon emission computed tomography (SPECT)/CT of the
      upper and lower body. Scans were evaluated visually by an intensity score (1-4)
      and quantitatively by the mean standardized uptake value (SUVmean) in thigh
      muscles after semi-automated segmentation of these. Furthermore, a SUVmean
      gradient down along the thighs was determined by linear regression of the slice
      by-slice activity. Interobserver analyses were performed on qualitative
      evaluations. Compared to controls, patients more often had a high intensity score
      (p < 0.0001), but interobserver analyses revealed only moderate agreement. The
      thigh muscular 99mTc-PYP activity (SUVmean) was 60% higher in patients than in
      controls, p < 0.0001, albeit with a wide range. There was an activity gradient
      down the thigh muscle, the proximal tracer uptake being highest, and this
      gradient was steeper in patients than in controls; the activity decreased by
      0.00024 and 0.00010 SUVmean mm-1, respectively, along the thighs. CONCLUSIONS:
      The muscular uptake of 99mTc-PYP was significantly higher in patients than in
      healthy controls by qualitative and quantitative assessment. The tracer uptake
      was higher in the proximal than in the distal part of the thigh muscle, and
      SUVmean gradients differed between groups. Hence, tomographic nuclear imaging
      allowing for quantification of the 99mTc-PYP uptake might contribute to the
      diagnosis of IIM, and SPECT/CT of the lower body might suffice.

PMID- 29222710
TI  - Assessment of Sulphate and Iron Contamination and Seasonal Variations in the
      Water Resources of a Damodar Valley Coalfield, India: A Case Study.
AB  - The aim of the present study was to assess the sulphate [Formula: see text] and
      iron (Fe) contamination and seasonal variations in the water resources
      (groundwater, surface water, and mine water) of the West Bokaro coalfield region,
      India. One hundred and twenty-four water resources samples were collected from
      the coalfield during the post- and pre-monsoon seasons. The concentrations of
      [Formula: see text] were determined using ion chromatography and Fe
      concentrations were analyzed using inductively coupled plasma mass spectrometry.
      A statistical analysis was used to easily understand the seasonal variations of
      the elements in the water resources of the area. The concentrations of [Formula:
      see text] and Fe in the water resources were higher in the pre-monsoon season
      than in the post-monsoon season, irrespective of location. The water resources of
      the coalfield were contaminated with high concentrations of [Formula: see text]
      and Fe, and would require suitable treatment before drinking, domestic and
      industrial uses.

PMID- 29222709
TI  - Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and
      Literature Review.
AB  - Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro,
      Brazil, is a main endemic area, with a large number of human and animal cases in
      the last 19 years. This mycosis is more frequently described in cats rather than
      in dogs. There are a limited number of oral antifungal agents for the treatment
      of sporotrichosis in animals. In this context, the effectiveness of terbinafine
      in the treatment of sporotrichosis in humans, as well as the promising results of
      in vitro susceptibility tests, inspired us to use this drug in the therapy of
      this mycosis in dogs. We reported for the first time the use of terbinafine in
      the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis.
      Moreover, we provided an overview of therapeutic features of canine
      sporotrichosis cases reported since the 1960s. One of the dogs presented the
      fixed cutaneous form of the disease, while the other patient presented hyperemia
      of the nasal mucosa and respiratory signs only. Terbinafine showed high
      antifungal activity in vitro against the canine Sporothrix isolates. The dogs
      were successfully treated with terbinafine, with remission of all clinical signs
      initially presented. The current reports indicate that this drug can emerge as a
      therapeutic option for canine sporotrichosis.

PMID- 29222711
TI  - OGRO survey on radiotherapy capacity in Austria : Status quo and estimation of
      future demands.
AB  - BACKGROUND: A comprehensive evaluation of the current national and regional
      radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030
      was performed by the Austrian Society for Radiation Oncology, Radiobiology and
      Medical Radiophysics (OGRO). MATERIALS AND METHODS: All Austrian centers provided
      data on the number of megavoltage (MV) units, treatment series, fractions,
      percentage of retreatments and complex treatment techniques as well as the daily
      operating hours for the year 2014. In addition, waiting times until the beginning
      of radiotherapy were prospectively recorded over the first quarter of 2015.
      National and international epidemiological prediction data were used to estimate
      future demands. RESULTS: For a population of 8.51 million, 43 MV units were at
      disposal. In 14 radiooncological centers, a total of 19,940 series with a mean
      number of 464 patients per MV unit/year and a mean fraction number of 20 (range
      16-24) per case were recorded. The average re-irradiation ratio was 14%. The
      survey on waiting times until start of treatment showed provision shortages in
      40% of centers with a mean waiting time of 13.6 days (range 0.5-29.3 days) and a
      mean maximum waiting time of 98.2 days. Of all centers, 21% had no or only a
      limited ability to deliver complex treatment techniques. Predictions for 2020 and
      2030 indicate an increased need in the overall number of MV units to a total of
      63 and 71, respectively. CONCLUSION: This OGRO survey revealed major regional
      differences in radiooncological capacity. Considering epidemiological
      developments, an aggravation of the situation can be expected shortly. This
      analysis serves as a basis for improved public regional health care planning.

PMID- 29222713
TI  - Comparative analysis of lactic acidosis induced by linezolid and vancomycin
      therapy using cohort and case-control studies of incidence and associated risk
      factors.
AB  - PURPOSE: Lactic acidosis is a rare complication of linezolid (LZD) therapy, and
      its incidence and risk factors remain unknown. This study aimed to compare the
      incidence of LZD-associated lactic acidosis (LALA) and vancomycin (VAN)
      associated lactic acidosis (VALA) and investigate the risk factors for LALA.
      METHODS: We performed a retrospective cohort study using propensity score-matched
      analyses comparing the incidence of lactic acidosis between LZD and VAN therapy.
      We included adult patients administered LZD or VAN between April 2014 and March
      2016 and extracted patient baseline data. In a case-control study, we identified
      the risk factors of lactic acidosis in patients treated with LZD. RESULTS: We
      identified 94 and 313 patients who were administered LZD and VAN, respectively.
      The incidence of lactic acidosis after LZD and VAN therapy was 10.6 and 0.3%,
      respectively. After propensity score-matched analyses, the incidence of lactic
      acidosis with LZD therapy was significantly higher than that with VAN therapy
      [10.0% (8/80) vs. 0% (0/80), respectively; risk difference, 0.1; 95% confidence
      interval (CI), 0.03-0.17; p = 0.004]. In a case-control study, 10 patients with
      LALA were matched to 20 non-lactic acidosis patients by age and sex. Patients
      with LALA were more likely to have renal insufficiency than non-lactic acidosis
      patients that were in the univariate analysis (odds ratio, 7.4; 95% CI, 1.0-84.4;
      p = 0.02). CONCLUSIONS: This study indicates that LALA occurs more frequently
      than VALA does and is associated with renal insufficiency. Therefore, close
      monitoring of kidney function and serum lactate is recommended during LZD
      therapy.

PMID- 29222712
TI  - Categorization and association analysis of risk factors for adverse drug events.
AB  - PURPOSE: Adverse drug events (ADE) are among the leading causes of morbidity and
      hospitalization. This review analyzes risk factors for ADE, particularly their
      categorizations and association patterns, the prevalence, severity, and
      preventability of ADE, and method characteristics of reviewed studies. METHODS:
      Literature search was conducted via PubMed, Science Direct, CINAHL, and MEDLINE.
      A review was conducted of research articles that reported original data about
      specific risk factors for ADE since 2000. Data analyses were performed using
      Excel and R. RESULTS: We summarized 211 risk factors for ADE, and grouped them
      into five main categories: patient-, disease-, medication-, health service-, and
      genetics-related. Among them, medication- and disease-related risk factors were
      most frequently studied. We further classified risk factors within each main
      category into subtypes. Among them, polypharmacy, age, gender, central nervous
      system agents, comorbidity, service utilization, inappropriate use/change use of
      drugs, cardiovascular agents, and anti-infectives were most studied subtypes. An
      association analysis of risk factors uncovered many interesting patterns. The
      median prevalence, preventability, and severity rate of reported ADE was 19.5%
      (0.29%~86.2%), 36.2% (2.63%~91%), and 16% (0.01%~47.4%), respectively.
      CONCLUSIONS: This review introduced new categories and subtypes of risk factors
      for ADE. The broad and in-depth coverage of risk factors and their association
      patterns elucidate the complexity of risk factor analysis. Managing risk factors
      for ADE is crucial for improving patient safety, particularly for the elderly,
      comorbid, and polypharmacy patients. Some under-explored risk factors such as
      genetics, mental health and wellness, education, lifestyle, and physical
      environment invite future research.

PMID- 29222714
TI  - Domperidone prolongs oral to duodenal transit time in video capsule endoscopy.
AB  - PURPOSE: Domperidone is thought to accelerate gastric emptying via D2 receptor
      antagonism at the gastro-oesophageal and gastro-duodenal junctions. Listed in the
      BNF as a prokinetic anti-emetic, it has been used in video capsule endoscopy
      (VCE) to accelerate capsule delivery to the small intestine. We audited VCEs
      performed at UHCW from 2011, when as standard practice, domperidone was given pre
      VCE, to 2012, after its discontinuation due to doubts about its effectiveness.
      METHODS: Thirty-one patients received oral domperidone 20 mg pre-VCE. Thirty
      three patients underwent VCE without domperidone pre-treatment. After 2 h, if the
      capsule remained intra-gastric, gastroscopy-assisted duodenal delivery was
      performed. Data was analysed using Mann-Whitney testing. RESULTS: Median oro
      duodenal transit was 13 and 30 min in the untreated and domperidone groups,
      respectively (p = 0.01). Median oro-caecal transit was 242 and 267 min in the
      untreated and domperidone groups, respectively (p = 0.02). No difference in
      duodenal-caecal transit was seen (p = 0.60). Six percent of untreated and 13% of
      domperidone VCEs required gastroscopy-assisted duodenal capsule delivery (p =
      0.65). CONCLUSIONS: Unexpectedly domperidone delayed VCE gastric transit. Most
      studies on domperidone prokinetic effects have been in diabetic gastroparesis,
      demonstrating that domperidone can achieve good symptomatic relief, but with
      mixed results for gastric emptying. Our study suggests that any antiemetic
      effects of domperidone are not mediated through accelerated gastric transit.

PMID- 29222716
TI  - Childhood acute disseminated encephalomyelitis: an Egyptian pilot study.
AB  - Describing the variable clinical features, laboratory findings, neuroimaging
      findings, and treatments given to children who presented with ADEM and following
      them up both clinically and radiologically. 21 patients were recruited: 14 new
      cases, and 7 old ones presenting over the preceding 5 years (retrospective review
      of existing data). 11 males and 10 females, with a mean age of 4.4 years +/- 2.7
      SD, were included. All new patients were subject to full history, examination and
      a panel of investigations including MRI of the brain. Treatment was given in the
      form of pulsed methyl prednisolone or intravenous immunoglobulin (IVIG), followed
      by clinical and radiological follow-up every 3 months as needed. 11 cases
      occurred in spring, 8 post vaccine, of which 5 were after oral polio vaccine
      (OPV). MRI was done for all 21 patients and was abnormal in all of them, CT was
      done in only 10 patients as was normal in 9. Hyponatremia was seen in 11
      patients. All patients who received corticosteroids showed prompt improvement. 6
      out of 10 patients who received IVIG first failed treatment. Of the 17 treated
      patients, 10 had no sequelae and 10 had total lesion resolution on MRI at 3
      months, versus 1 and 0 patients, respectively, in the untreated group. We found a
      disproportionately large number of post vaccination cases, especially after OPV.
      The association of ADEM with hyponatremia needs further study. MRI is central to
      diagnosis. Outcome is much better with treatment with steroids being far superior
      to IVIG. Excess use of IVIG should be discouraged.

PMID- 29222715
TI  - Clinical validation study of dried blood spot for determining everolimus
      concentration in patients with cancer.
AB  - PURPOSE: Everolimus treatment is seriously hampered by its toxicity profile. As a
      relationship between everolimus exposure and effectiveness and toxicity has been
      established, early and ongoing concentration measurement can be key to
      individualize the dose and optimize treatment outcomes. Dried blood spot (DBS)
      facilitates sampling at a patients' home and thereby eases dose
      individualization. The aim of this study is to determine the agreement and
      predictive performance of DBS compared to whole blood (WB) to measure everolimus
      concentrations in cancer patients. METHODS: Paired DBS and WB samples were
      collected in 22 cancer patients treated with everolimus and analyzed using UPLC
      MS/MS. Bland-Altman and Passing-Bablok analysis were used to determine method
      agreement. Limits of clinical relevance were set at a difference of +/- 25%, as
      this would lead to a different dosing advice. Using DBS concentration and Passing
      Bablok regression analysis, WB concentrations were predicted. RESULTS: Samples of
      20 patients were suitable for analysis. Bland-Altman analysis showed a mean ratio
      of everolimus WB to DBS concentrations of 0.90, with 95% of data points within
      limits of clinical relevance. Passing-Bablok regression of DBS compared to WB
      revealed no constant bias (intercept 0.02; 95% CI 0.93-1.35) and a small
      proportional bias (slope 0.89; 95% CI 0.76-0.99). Predicted concentrations showed
      low bias and imprecision and 90% of samples had an absolute percentage prediction
      error of < 20%. CONCLUSIONS: DBS is a valid method to determine everolimus
      concentrations in cancer patients. This can especially be of value for early
      recognition of over- or underexposure to enable dose adaptations.

PMID- 29222717
TI  - Correction to: Peak stresses shift from femoral tunnel aperture to tibial tunnel
      aperture in lateral tibial tunnel ACL reconstructions: a 3D graft-bending angle
      measurement and finite-element analysis.
AB  - Unfortunately, one of the co-author's name was missed in the original online
      publication of this article. The name should be included as sixth author in the
      author group.

PMID- 29222718
TI  - Treatment of stress urinary incontinence with a mobile app: factors associated
      with success.
AB  - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence is common among women.
      First-line treatment includes pelvic floor muscle training (PFMT) and lifestyle
      advice, which can be provided via a mobile app. The efficacy of app-based
      treatment has been demonstrated in a randomized controlled trial (RCT). In this
      study, we aimed to analyze factors associated with successful treatment. METHODS:
      Secondary analysis of data from the RCT. At baseline and 3-month follow-up,
      participants (n = 61) answered questions about symptoms, quality of life,
      background, and PFMT. Success was defined as rating the condition as much or very
      much better according to the validated Patient Global Impression of Improvement
      questionnaire. Factors possibly associated with success were analyzed with
      univariate logistic regression; if p < 0.20, the factor was entered into a
      multivariate model that was adjusted for age. Variables were then removed
      stepwise. RESULTS: At follow-up, 34 out of 61 (56%) of participants stated that
      their condition was much or very much better. Three factors were significantly
      associated with success: higher expectations for treatment (odds ratio [OR]
      11.38, 95% confidence interval [CI] 2.02-64.19), weight control (OR 0.44 per kg
      gained, 95% CI 0.25-0.79), and self-rated improvement of pelvic floor muscle
      strength (OR 35.54, 95% CI 4.96-254.61). Together, these factors accounted for
      61.4% (Nagelkerke R2) of the variability in success. CONCLUSION: These results
      indicate that app-based treatment effects are better in women who are interested
      in and have high expectations of such treatment. Also, the findings underline the
      importance of strengthening the pelvic floor muscles and offering lifestyle
      advice.

PMID- 29222719
TI  - Longevity of visual improvements following transcorneal electrical stimulation
      and efficacy of retreatment in three individuals with retinitis pigmentosa.
AB  - PURPOSE: A small-scale randomized controlled trial conducted by our group found
      that four of seven retinitis pigmentosa (RP) subjects who received six weekly
      Transcorneal Electrical Stimulation (TES) sessions developed significant
      improvements in visual acuity (VA), quick contrast sensitivity function (qCSF),
      and/or Goldmann visual fields (GVF). We longitudinally monitored three of these
      participants for declining visual function due to natural RP progression to
      determine the duration of their responses and administered retreatments. METHODS:
      Over a period of 29-35 months, repeated ETDRS VA, qCSF and/or GVF tests and three
      to six TES treatment courses consisting of six weekly sessions were administered
      in each eye of three RP participants every four to 16 months in an unmasked,
      prospective case series study. RESULTS: For two participants, there were
      significant VA improvements of 44-52 letters (0.88-1.04 logMAR) and 15-23 letters
      (0.3-0.46 logMAR) in the worse eye at baseline after each of three or four
      treatment courses of TES compared to initial baseline. They had no significant
      decreases from baseline for VA or qCSF over 29 to 35 months, The third
      participant had a significant mean improvement in VA in the eye with better
      baseline vision (p = 0.004) and binocularly (p < 0.001) following six treatment
      courses over the 29-month period. For the first two participants, mean annual
      rates of GVF change for each eye ranged from -5% to 0% with the V4e stimulus, and
      -26% to +33% the III4e stimulus. The third participant's mean annual GVF changes
      were +14 to +35%, with a statistically significant improvement across 29 months
      for both the V4e and III4e stimuli in the right eye (p = 0.045; p = 0.015) and
      the V4e stimulus in the left eye (p = 0.047). CONCLUSION: Following encouraging
      visual improvements after TES that lasted for several months, it appears it may
      be possible to restore and prevent slowly diminishing vision over time with
      retreatments, which requires confirmation in a large-scale randomized controlled
      trial.

PMID- 29222720
TI  - Reproductive ecology of a parasitic plant differs by host species: vector
      interactions and the maintenance of host races.
AB  - Parasitic plants often attack multiple host species with unique defenses,
      physiology, and ecology. Reproductive phenology and vectors of parasitic plant
      genes (pollinators and dispersers) can contribute to or erode reproductive
      isolation of populations infecting different host species. We asked whether
      desert mistletoe, Phoradendron californicum (Santalaceae tribe Visceae syn.
      Viscaceae), differs ecologically across its dominant leguminous hosts in ways
      affecting reproductive isolation. Parasite flowering phenology on one host
      species (velvet mesquite, Prosopis velutina) differed significantly from that on
      four others, and phenology was not predicted by host species phenology or host
      individual. Comparing mistletoe populations on mesquite and another common host
      species (catclaw acacia, Senegalia greggii) for which genetically distinct host
      races are known, we tested for differences in interactions with vectors by
      quantifying pollinator visitation, reward production, pollen receipt, and fruit
      consumption. Mistletoes on mesquite produced more pollinator rewards per flower
      (1.86 times the nectar and 1.92 times the pollen) and received ~ 2 more pollen
      grains per flower than those on acacia. Mistletoes on the two host species
      interacted with distinct but overlapping pollinator communities, and pollinator
      taxa differed in visitation according to host species. Yet, mistletoes of neither
      host showed uniformly greater reproductive success. Fruit set (0.70) did not
      differ by host, and the rates of fruit ripening and removal differed in
      contrasting ways. Altogether, we estimate strong but asymmetric pre-zygotic
      isolating barriers between mistletoes on the two hosts. These host-associated
      differences in reproduction have implications for interactions with mutualist
      vectors and population genetic structure.

PMID- 29222721
TI  - Are the adverse effects of stressors on amphibians mediated by their effects on
      stress hormones?
AB  - Adverse effects of anthropogenic changes on biodiversity might be mediated by
      their impacts on the stress response of organisms. To test this hypothesis, we
      crossed exposure to metyrapone, a synthesis inhibitor of the stress hormone
      corticosterone, with exposure to the herbicide atrazine and the fungal pathogen
      Batrachochytrium dendrobatidis (Bd) to assess whether the effects of these
      stressors on tadpoles and post-metamorphic frogs were mediated by corticosterone.
      Metyrapone countered atrazine- and Bd-induced corticosterone elevations. However,
      atrazine- and Bd-induced reductions in body size were not mediated by
      corticosterone because they persisted despite metyrapone exposure. Atrazine
      lowered Bd abundance without metyrapone but increased Bd abundance with
      metyrapone for tadpoles and frogs. In contrast, atrazine reduced tolerance of Bd
      infections because frogs exposed to atrazine as tadpoles had reduced growth with
      Bd compared to solvent controls; this effect was not countered by metyrapone. Our
      results suggest that the adverse effects of atrazine and Bd on amphibian growth,
      development, and tolerance of infection are not mediated primarily by
      corticosterone. A possible mechanism for these effects is energy lost from
      atrazine detoxification, defense against Bd, or repair from damage caused by
      atrazine and Bd. Additional studies are needed to evaluate how often the effects
      of anthropogenic stressors are mediated by stress hormones.

PMID- 29222722
TI  - Binaural auditory beats affect long-term memory.
AB  - The presentation of two pure tones to each ear separately with a slight
      difference in their frequency results in the perception of a single tone that
      fluctuates in amplitude at a frequency that equals the difference of interaural
      frequencies. This perceptual phenomenon is known as binaural auditory beats, and
      it is thought to entrain electrocortical activity and enhance cognition functions
      such as attention and memory. The aim of this study was to determine the effect
      of binaural auditory beats on long-term memory. Participants (n = 32) were kept
      blind to the goal of the study and performed both the free recall and recognition
      tasks after being exposed to binaural auditory beats, either in the beta (20 Hz)
      or theta (5 Hz) frequency bands and white noise as a control condition. Exposure
      to beta-frequency binaural beats yielded a greater proportion of correctly
      recalled words and a higher sensitivity index d' in recognition tasks, while
      theta-frequency binaural-beat presentation lessened the number of correctly
      remembered words and the sensitivity index. On the other hand, we could not find
      differences in the conditional probability for recall given recognition between
      beta and theta frequencies and white noise, suggesting that the observed changes
      in recognition were due to the recollection component. These findings indicate
      that the presentation of binaural auditory beats can affect long-term memory both
      positively and negatively, depending on the frequency used.

PMID- 29222723
TI  - Respiration-coupled rhythms in prefrontal cortex: beyond if, to when, how, and
      why.

PMID- 29222724
TI  - Nasal respiration entrains delta-frequency oscillations in the prefrontal cortex
      and hippocampus of rodents.

PMID- 29222725
TI  - Taming the oscillatory zoo in the hippocampus and neo-cortex: a review of the
      commentary of Lockmann and Tort on Roy et al.

PMID- 29222726
TI  - Non-auditory, electrophysiological potentials preceding dolphin biosonar click
      production.
AB  - The auditory brainstem response to a dolphin's own emitted biosonar click can be
      measured by averaging epochs of the instantaneous electroencephalogram (EEG) that
      are time-locked to the emitted click. In this study, averaged EEGs were measured
      using surface electrodes placed on the head in six different configurations while
      dolphins performed an echolocation task. Simultaneously, biosonar click emissions
      were measured using contact hydrophones on the melon and a hydrophone in the
      farfield. The averaged EEGs revealed an electrophysiological potential (the pre
      auditory wave, PAW) that preceded the production of each biosonar click. The
      largest PAW amplitudes occurred with the non-inverting electrode just right of
      the midline-the apparent side of biosonar click generation-and posterior of the
      blowhole. Although the source of the PAW is unknown, the temporal and spatial
      properties rule out an auditory source. The PAW may be a neural or myogenic
      potential associated with click production; however, it is not known if muscles
      within the dolphin nasal system can be actuated at the high rates reported for
      dolphin click production, or if sufficiently coordinated and fast motor endplates
      of nasal muscles exist to produce a PAW detectable with surface electrodes.

PMID- 29222727
TI  - A method for facilitating the seed germination of a mycoheterotrophic orchid,
      Gastrodia pubilabiata, using decomposed leaf litter harboring a basidiomycete
      fungus, Mycena sp.
AB  - BACKGROUND: Mycoheterotrophic plants are one of the most difficult plant groups
      to conserve because they are entirely dependent on symbiotic fungi. Establishment
      of viable culture systems would greatly aid their conservation. We describe a
      simple culture system for the mycoheterotrophic orchid, Gastrodia pubilabiata,
      that does not require laboratory facilities. The orchid is symbiotic with leaf
      litter-decomposing fungi. RESULTS: Gastrodia pubilabiata seeds were incubated in
      plastic boxes or glass bottles filled with leaf litter collected from the natural
      habitat of the species. Seed germination was observed after 35 days and seedling
      development followed. Fungal isolates from seedlings were identified as
      Mycenaceae (Basidiomycota), a leaf-litter-decomposing mycorrhizal fungus of
      Gastrodia species. CONCLUSION: Our method can be used to conserve endangered
      mycoheterotrophic plants associated with leaf litter-decomposing fungi
      efficiently, and can also serve as a model system for physiological and molecular
      studies of such plants.

PMID- 29222728
TI  - Fetal Electrocardiogram Extraction and Analysis Using Adaptive Noise Cancellation
      and Wavelet Transformation Techniques.
AB  - Birth defect-related demise is mainly due to congenital heart defects. In the
      earlier stage of pregnancy, fetus problem can be identified by finding
      information about the fetus to avoid stillbirths. The gold standard used to
      monitor the health status of the fetus is by Cardiotachography(CTG), cannot be
      used for long durations and continuous monitoring. There is a need for continuous
      and long duration monitoring of fetal ECG signals to study the progressive health
      status of the fetus using portable devices. The non-invasive method of
      electrocardiogram recording is one of the best method used to diagnose fetal
      cardiac problem rather than the invasive methods.The monitoring of the fECG
      requires development of a miniaturized hardware and a efficient signal processing
      algorithms to extract the fECG embedded in the mother ECG. The paper discusses a
      prototype hardware developed to monitor and record the raw mother ECG signal
      containing the fECG and a signal processing algorithm to extract the fetal
      Electro Cardiogram signal. We have proposed two methods of signal processing,
      first is based on the Least Mean Square (LMS) Adaptive Noise Cancellation
      technique and the other method is based on the Wavelet Transformation technique.
      A prototype hardware was designed and developed to acquire the raw ECG signal
      containing the mother and fetal ECG and the signal processing techniques were
      used to eliminate the noises and extract the fetal ECG and the fetal Heart Rate
      Variability was studied. Both the methods were evaluated with the signal acquired
      from a fetal ECG simulator, from the Physionet database and that acquired from
      the subject. Both the methods are evaluated by finding heart rate and its
      variability, amplitude spectrum and mean value of extracted fetal ECG. Also the
      accuracy, sensitivity and positive predictive value are also determined for fetal
      QRS detection technique. In this paper adaptive filtering technique uses Sign
      sign LMS algorithm and wavelet techniques with Daubechies wavelet, employed along
      with de noising techniques for the extraction of fetal Electrocardiogram.Both the
      methods are having good sensitivity and accuracy. In adaptive method the
      sensitivity is 96.83, accuracy 89.87, wavelet sensitivity is 95.97 and accuracy
      is 88.5. Additionally, time domain parameters from the plot of heart rate
      variability of mother and fetus are analyzed.

PMID- 29222730
TI  - Morphology and morphometry of lacrimal drainage system in relation to bony
      landmarks in Caucasian adults: a cadaveric study.
AB  - PURPOSE: The objective of this study is to examine the morphometry of the
      lacrimal drainage system with reference to bony landmarks in the vicinity.
      METHODS: Twenty midsaggitalized heads obtained from sixteen preserved cadavers
      were studied. Measurements involved detailed morphometry of anterior and
      posterior lacrimal crests, bony lacrimal sac fossa, entrance and length of the
      bony nasolacrimal duct (NLD), attachment of Horner's muscle, and characteristics
      of the inferior meatal opening of the NLD. RESULTS: The mean lengths of anterior
      and posterior lacrimal crests were 16.3 and 12.5 mm, respectively. At the
      midpoint of the posterior lacrimal crest, Horner's muscle was found to be
      attached at a mean of 1.3 mm posterior to the crest. The mean dimensions of the
      bony lacrimal sac fossa at superior, mid and inferior levels were 6.5, 8.7, and
      5.9 mm, respectively. The mean contribution of the lacrimal bone to the lacrimal
      sac fossa was 56.2%. The mean anteroposterior and transverse diameters of the
      entrance of the bony NLD were 5.7 and 4.7 mm, respectively. The most common type
      of NLD opening in the inferior meatus was that of "vertical sulcus" (70%, 14/20).
      The mean distance of the NLD opening from the anterior nasal spine and Limen nasi
      were 22.2 and 18.9 mm, respectively. CONCLUSION: This study provides useful
      anatomical and positional relationship of bony lacrimal landmarks and
      nasolacrimal duct in Caucasian adults.

PMID- 29222729
TI  - Coding of time-dependent stimuli in homogeneous and heterogeneous neural
      populations.
AB  - We compare the information transmission of a time-dependent signal by two types
      of uncoupled neuron populations that differ in their sources of variability: i) a
      homogeneous population whose units receive independent noise and ii) a
      deterministic heterogeneous population, where each unit exhibits a different
      baseline firing rate ('disorder'). Our criterion for making both sources of
      variability quantitatively comparable is that the interspike-interval
      distributions are identical for both systems. Numerical simulations using leaky
      integrate-and-fire neurons unveil that a non-zero amount of both noise or
      disorder maximizes the encoding efficiency of the homogeneous and heterogeneous
      system, respectively, as a particular case of suprathreshold stochastic
      resonance. Our findings thus illustrate that heterogeneity can render similarly
      profitable effects for neuronal populations as dynamic noise. The optimal
      noise/disorder depends on the system size and the properties of the stimulus such
      as its intensity or cutoff frequency. We find that weak stimuli are better
      encoded by a noiseless heterogeneous population, whereas for strong stimuli a
      homogeneous population outperforms an equivalent heterogeneous system up to a
      moderate noise level. Furthermore, we derive analytical expressions of the
      coherence function for the cases of very strong noise and of vanishing intrinsic
      noise or heterogeneity, which predict the existence of an optimal noise
      intensity. Our results show that, depending on the type of signal, noise as well
      as heterogeneity can enhance the encoding performance of neuronal populations.

PMID- 29222731
TI  - Predictors of long-term care among nonagenarians: the Vitality 90 + Study with
      linked data of the care registers.
AB  - BACKGROUND: The need for long-term care services increases with age. However,
      little is known about the predictors of long-term care (LTC) entry among the
      oldest old. AIMS: Aim of this study was to assess predictors of LTC entry in a
      sample of men and women aged 90 years and older. METHODS: This study was based on
      the Vitality 90 + Study, a population-based study of nonagenarians in the city of
      Tampere, Finland. Baseline information about health, functioning and living
      conditions were collected by mailed questionnaires. Information about LTC was
      drawn from care registers during the follow-up period extending up to 11 years.
      Cox regression models were used for the analyses, taking into account the
      competing risk of mortality. RESULTS: During the mean follow-up period of 2.3
      years, 844 (43%) subjects entered first time into LTC. Female gender (HR 1.39,
      95% CI 1.14-1.69), having at least two chronic conditions (HR 1.24, 95% CI 1.07
      1.44), living alone (HR 1.37, 95% CI 1.15-1.63) and help received sometimes (HR
      1.23, 95% CI 1.02-1.49) or daily (HR 1.68, 95% CI 1.38-2.04) were independent
      predictors of LTC entry. CONCLUSION: Risk of entering into LTC was increased
      among women, subjects with at least two chronic conditions, those living alone
      and with higher level of received help. Since number of nonagenarians will
      increase and the need of care thereby, it is essential to understand predictors
      of LTC entry to offer appropriate care for the oldest old in future.

PMID- 29222732
TI  - 46th ESCP symposium on clinical pharmacy "Science meets practice: towards
      evidence-based clinical pharmacy services", Heidelberg, Germany, October 9th
      11th, 2017.

PMID- 29222733
TI  - Frail older people with multi-morbidities in primary care: a new integrated care
      clinical pharmacy service.
AB  - Background Older people confined to their own homes due to frailty, multiple
      longterm conditions and/or complex needs, are known to be at risk of medicines
      related problems. Whilst a health and social care team approach to supporting
      these patients is advocated, there is limited evidence regarding how pharmacists
      can best contribute. Objective To describe a new specialist pharmacy service
      (called the integrated care clinical pharmacist) in terms of how it works, what
      it achieves and its policy implications. Setting Patients' own homes in Lambeth,
      London, UK. Method Community matrons identified patients who were experiencing
      medicines related problems. These were referred to the integrated care clinical
      pharmacist who undertook a full medication review and recorded activities, which
      were independently analysed anonymously. Main outcome measure Medicines-related
      problems and the associated interventions. Result 143 patients were referred to
      the service over a 15-month period. A total of 376 medicines-related problems
      were identified: 28 (7%) supply issues, 107 (29%) compliance issues, 241 (64%)
      clinical issues. A diverse range of interventions were instigated by the
      pharmacist, requiring the coordination of community pharmacists, primary and
      secondary health and social care professionals. Conclusion This project
      demonstrated that including an integrated care clinical pharmacy service as part
      of the health and social care team that visits frail, older people in their own
      homes has benefits. The service operated as part of a wider inter-professional
      community team. The service also supported current health policy priorities in
      medicines optimization by identifying and addressing a wide range of medicines
      related problems for this vulnerable patient group.

PMID- 29222734
TI  - TERT promoter hotspot mutations in breast cancer.
AB  - BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have been
      discovered in solid and hematological malignancies, where they reflect TERT
      activation and cell-cycle progression. In melanoma, glioma, and thyroid cancers,
      TERT promoter mutations are associated with a poor prognosis. However, no studies
      have evaluated the prevalence and prognostic significance of TERT promoter
      mutations in breast cancer. METHODS: We analyzed TERT promoter hotspot mutations
      (C228T and C250T) using direct sequencing of DNA from 319 tumor tissues. We also
      collected clinical data from cases that were positive for TERT promoter
      mutations. RESULTS: We detected TERT promoter mutations in three (0.9%) of the
      319 cases. Two patients had hormone receptor-positive and human epidermal growth
      factor receptor 2-negative cancer, while the third patient had triple-negative
      cancer. All three patients had initially been diagnosed with operable breast
      cancer and undergone surgical treatment. The relapse-free survivals of these
      patients were 83, 226, and 270 months, respectively. The mutations were C250T in
      the triple-negative cancer case and C228T in the remaining two cases. CONCLUSION:
      Given the rarity of TERT promoter mutations, further studies are needed to
      confirm their prognostic significance in breast cancer cases.

PMID- 29222735
TI  - Delayed perforation after endoscopic submucosal dissection treated successfully
      by temporary stent placement.
AB  - A 71-year-old male patient with a long-segment (C10M12) Barrett's esophagus
      harboring multifocal high-grade dysplasia was referred to our clinic. After a
      multidisciplinary team conference and the patient's informed consent, an
      endoscopic submucosal dissection (ESD) was performed with resection of 4/5 of the
      esophageal circumference along 12 cm, without any complications during or
      immediately after the procedure. In the day after the ESD, the patient presented
      suddenly with dyspnea and subcutaneous emphysema in the neck and chest. A
      computed tomography (CT) showed subcutaneous emphysema in the neck and
      pneumomediastinum, confirming the diagnosis of delayed perforation. There was
      gradual progression into respiratory failure with the need for ventilatory
      support. Endoscopic treatment was decided and 2 fully covered self-expandable
      metal stents were deployed in the esophagus. Patient's clinical condition
      improved and oral diet was resumed at day 7. Stents were retrieved at day 12 and
      there were no strictures on the 2 and 6-month follow-ups. This is the first
      report of delayed perforation after endoscopic submucosal disection in the
      esophagus that was successfully managed with endoscopic therapy.

PMID- 29222736
TI  - Usefulness and limitations of dual-layer spectral detector computed tomography
      for diagnosing biliary stones not detected by conventional computed tomography: a
      report of three cases.
AB  - Computed tomography (CT) is useful for diagnosing biliary stones. However, the
      presence of stones not detected by conventional CT, such as iso-dense stones with
      CT numbers similar to those of bile or small stones, is problematic. Although
      conventional CT provides only 120-kVp images corresponding to CT numbers at
      approximately 70 keV, dual-layer spectral detector CT uses one X-ray source and
      dual-layer detectors to collect low- and high-energy data simultaneously;
      retrospective spectral analysis, including virtual monochromatic images with
      photon energy levels of 40-200 keV, material decomposition images, and spectral
      curves, can be immediately performed on demand. This technique can immediately
      discriminate between materials with similar conventional CT numbers. Therefore,
      prompt and accurate diagnosis of iso-dense stones can be performed. In two out of
      three of our cases, iso-dense stones were detected in virtual monochromatic
      images at 40 keV, but in the remaining case a common 4-mm bile duct stone was not
      detected on 120-kVp and 40-keV images by retrospective spectral analysis.
      However, this stone was detected by magnetic resonance cholangiopancreatography.
      Retrospective spectral analysis using dual-layer spectral detector CT was useful
      for prompt and accurate diagnosis of iso-dense stones, but detection of <5-mm
      stones may be a limitation of this technique and of conventional CT.

PMID- 29222737
TI  - Differences by Sexual Orientation in Perceptions of Neighborhood Cohesion:
      Implications for Health.
AB  - A large body of research documents the relationship between health and place,
      including the positive association between neighborhood cohesion and health.
      However, very little research has examined neighborhood cohesion by sexual
      orientation. This paper addresses that gap by examining differences in perceived
      neighborhood cohesion by sexual orientation. We use data from the 2016 National
      Health Interview Survey (n = 28,164 respondents aged 18 years and older) to
      examine bivariate differences by sexual orientation in four measures of
      neighborhood cohesion. We then use ordered logistic regression models to assess
      the relationship between sexual orientation and a scaled measure of neighborhood
      cohesion, adjusting for socio-demographic characteristics, living arrangements,
      health status, region, and neighborhood tenure. We find that lesbian, gay, and
      bisexual (LGB) adults are less likely to say that they live in a close-knit
      neighborhood (54.6 vs. 65.6%, p < 0.001), they can count on their neighbors (74.7
      vs. 83.1%, p < 0.001), they trust their neighbors (75.5 vs. 83.7%, p < 0.001), or
      people in their neighborhood help each other out (72.9 vs. 83.1%, p < 0.001),
      compared to heterosexual adults. Even after controlling for socio-demographic
      factors, neighborhood cohesion scores are lower for LGB adults compared to
      heterosexual adults (odds ratio of better perceived neighborhood cohesion for
      sexual minorities: 0.70, p < 0.001). Overall, LGB adults report worse
      neighborhood cohesion across multiple measures, even after adjusting for
      individual characteristics and neighborhood tenure. Because living in a cohesive
      neighborhood is associated with better health outcomes, future research,
      community-level initiatives, and public policy efforts should focus on creating
      welcoming neighborhood environments for sexual minorities.

PMID- 29222738
TI  - CT based 3D printing is superior to transesophageal echocardiography for pre
      procedure planning in left atrial appendage device closure.
AB  - Accurate assessment of the left atrial appendage (LAA) is important for pre
      procedure planning when utilizing device closure for stroke reduction. Sizing is
      traditionally done with transesophageal echocardiography (TEE) but this is not
      always precise. Three-dimensional (3D) printing of the LAA may be more accurate.
      24 patients underwent Watchman device (WD) implantation (71 +/- 11 years, 42%
      female). All had complete 2-dimensional TEE. Fourteen also had cardiac computed
      tomography (CCT) with 3D printing to produce a latex model of the LAA for pre
      procedure planning. Device implantation was unsuccessful in 2 cases (one with and
      one without a 3D model). The model correlated perfectly with implanted device
      size (R2 = 1; p < 0.001), while TEE-predicted size showed inferior correlation
      (R2 = 0.34; 95% CI 0.23-0.98, p = 0.03). Fisher's exact test showed the model
      better predicted final WD size than TEE (100 vs. 60%, p = 0.02). Use of the model
      was associated with reduced procedure time (70 +/- 20 vs. 107 +/- 53 min, p =
      0.03), anesthesia time (134 +/- 31 vs. 182 +/- 61 min, p = 0.03), and fluoroscopy
      time (11 +/- 4 vs. 20 +/- 13 min, p = 0.02). Absence of peri-device leak was also
      more likely when the model was used (92 vs. 56%, p = 0.04). There were trends
      towards reduced trans-septal puncture to catheter removal time (50 +/- 20 vs. 73
      +/- 36 min, p = 0.07), number of device deployments (1.3 +/- 0.5 vs. 2.0 +/- 1.2,
      p = 0.08), and number of devices used (1.3 +/- 0.5 vs. 1.9 +/- 0.9, p = 0.07).
      Patient specific models of the LAA improve precision in closure device sizing.
      Use of the printed model allowed rapid and intuitive location of the best landing
      zone for the device.

PMID- 29222739
TI  - Effects of two aerobic exercise training protocols on parameters of oxidative
      stress in the blood and liver of obese rats.
AB  - We evaluated the effects of moderate-intensity continuous training (MICT) and
      high-intensity interval training (HIIT) protocols on the alterations in oxidative
      stress parameters caused by a high-fat diet (HFD), in the blood and liver of
      rats. The HFD enhanced thiobarbituric acid reactive substances (TBA-RS) and
      protein carbonyl content, while reducing total sulfhydryl content and catalase
      (CAT) and glutathione peroxidase (GSH-Px) activities in the blood. Both training
      protocols prevented an increase in TBA-RS and protein carbonyl content, and
      prevented a reduction in CAT. HIIT protocol enhanced SOD activity. In the liver,
      HFD didn't alter TBA-RS, total sulfhydryl content or SOD, but increased protein
      carbonyl content and CAT and decreased GSH-Px. The exercise protocols prevented
      the increase in protein carbonyl content and the MICT protocol prevented an
      alteration in CAT. In conclusion, HFD elicits oxidative stress in the blood and
      liver and both protocols prevented most of the alterations in the oxidative
      stress parameters.

PMID- 29222740
TI  - A Case of Maturity Onset Diabetes of the Young (MODY3) in a Family with a Novel
      HNF1A Gene Mutation in Five Generations.
AB  - Diabetes mellitus with autosomal dominant inheritance, i.e., maturity-onset
      diabetes of the young (MODY), is a genetic form of diabetes mellitus. The MODY
      phenotype is associated with gene mutations leading to pancreatic beta-cell
      dysfunction. Here, we present the clinical case of a 50-year-old proband with
      familial diabetes mellitus in five generations (proband, her mother, grandmother,
      great-grandfather, and son). This disease is most likely associated with the
      novel Ser6Arg mutation in the HNF1A gene, which was identified in four family
      members. The mutation was not detected in MODY patients (126 subjects), in
      patients with type 2 diabetes mellitus (188 subjects), and in a general
      population sample (564 subjects).

PMID- 29222741
TI  - Exploratory study of barriers to successful office contacts for attention deficit
      hyperactivity disorder.
AB  - The American Academy of Pediatrics published attention deficit hyperactivity
      disorder (ADHD) guidelines, but significant variability exists in care. This
      exploratory study aimed to understand barriers to compliance with primary care
      office contacts for ADHD medication management. The study was conducted at a
      single academic medical center via retrospective chart review between 6/1/15 and
      5/31/16 in combination with telephone interviews. Participants included 306
      children 6-12 years old with an ADHD-related ICD-9/ICD-10 diagnosis. Factors
      affecting compliance were assessed via multivariable linear regression using the
      outcome of unsuccessful office contacts based on the percentage of missed,
      canceled, or rescheduled appointments. ADHD patients averaged 28.3% (SD 23.8%)
      unsuccessful office contacts. Unsuccessful contacts significantly increased by
      15% for Hispanic ethnicity, 8% for public insurance, 8% for inattentive subtype,
      and 3% for every 10 miles additional distance from the office. Telephone
      interviews were attempted for those missing >= 3 appointments, which represented
      18.3% (56/306) of the sample. Interviews were successfully completed with 37.5%
      (21/56). Of these, 52.3% (11/21) of parents preferred in-person visits.
      Structural barriers were not a concern, but 52.3% (11/21) reported high caregiver
      strain and fatigue. The results indicate that cultural barriers to understanding
      of ADHD and its management must be reconsidered. Use of Internet-based platforms
      may be a novel approach to address issues of distance, financial difficulty, and
      parental stress.

PMID- 29222742
TI  - Protecting Participants in Thought Experiments: The Role of the Research Ethics
      Committee.

PMID- 29222743
TI  - ?

PMID- 29222744
TI  - Activation of intestinal GR-FXR and PPARalpha-UGT signaling exacerbates ibuprofen
      induced enteropathy in mice.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury
      (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there
      is no proven-effective treatment for NSAID enteropathy, and its underlying
      mechanism remains obscure. The present study showed that glucocorticoids are an
      important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75
      mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200 mg/kg) in
      the small intestine of mice, which was not due to the pregnane-X-receptor
      pathway. Instead, glucocorticoid receptor (GR) mediated the effect of DEX (5
      mg/kg) on both the acute (200 mg/kg) and 7-day repeated-dose (50 mg/kg) toxicity
      of IBU in the small intestine. Combined treatment of DEX (5 mg/kg) and IBU (50
      mg/kg) synergistically repressed the intestinal farnesoid X receptor (FXR)
      cystathionine-gamma-lyase signaling, which was accompanied with an elevation in
      the biliary excretion of bile acids, especially the FXR antagonist tauro-beta
      muricholic acid. DEX (5 mg/kg) also activated intestinal peroxisome proliferator
      activated receptor alpha (PPARalpha)-UDP-glucuronosyltransferase (UGT) pathway,
      which increased the formation and enterohepatic circulation of IBU-acyl
      glucuronide. Furthermore, DEX (5 mg/kg) and IBU (50 mg/kg) altered the intestinal
      microbial composition, characterized with a marked decrease in Actinobacteria. To
      conclude, the present study for the first time suggests that glucocorticoids play
      vital roles in control of IBU enteropathy via intestinal GR-FXR and PPARalpha-UGT
      signaling.

PMID- 29222745
TI  - MiR-26a functions as a tumor suppressor in ambient particulate matter-bound metal
      triggered lung cancer cell metastasis by targeting LIN28B-IL6-STAT3 axis.
AB  - Exposure to ambient particulate matter (PM) has been linked to the increasing
      incidence and mortality of lung cancer, but the principal toxic components and
      molecular mechanism remain to be further elucidated. In this study, human lung
      adenocarcinoma A549 cells were treated with serial concentrations of water
      extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that
      exposure to 25 and 50 MUg/ml of WE-PM10 for 48 h significantly suppressed miR-26a
      to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6
      (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549
      cells, subsequently contributing to enhanced epithelial-mesenchymal transition
      and accelerated migration and invasion. In vivo pulmonary colonization assay
      further indicated that WE-PM10 enhanced the metastatic ability of A549 cells. In
      addition, luciferase reporter assay demonstrated that 3' untranslated region of
      LIN28B was a direct target of miR-26a. Last but not the least, the key toxic
      contribution of metals in WE-PM10 was confirmed by the finding that removal of
      metals through chelation significantly rescued WE-PM10-mediated inflammatory,
      carcinogenic and metastatic responses. Taken together, miR-26a could act as the
      tumor suppressor in PM10-related lung cancer, and PM10-bound metals promoted lung
      cancer cell metastasis through downregulation of miR-26a that directly mediated
      LIN28B expression.

PMID- 29222746
TI  - Cadmium favors F-actin depolymerization in rat renal mesangial cells by site
      specific, disulfide-based dimerization of the CAP1 protein.
AB  - Cadmium is a toxic metal that produces oxidative stress and has been shown to
      disrupt the actin cytoskeleton in rat renal mesangial cells (RMC). In a survey of
      proteins that might undergo Cd2+-dependent disulfide crosslinking, we identified
      the adenylyl cyclase-associated protein, CAP1, as undergoing a dimerization in
      response to Cd2+ (5-40 uM) that was sensitive to disulfide reducing agents, was
      reproduced by the disulfide crosslinking agent diamide, and was shown by site
      directed mutagenesis to involve the Cys29 residue of the protein. Reactive oxygen
      species are not involved in the thiol oxidation, and glutathione modulates
      background levels of dimer. CAP1 is known to enhance cofilin's F-actin severing
      activity through binding to F-actin and cofilin. F-actin sedimentation and GST
      cofilin pulldown studies of CAP1 demonstrated enrichment of the CAP1 dimer's
      association with cofilin, and in the cofilin-F-actin pellet, suggesting that Cd2+
      induced dimer increases the formation of a CAP1-cofilin-F-actin complex. Both
      siRNA-based silencing of CAP1 and overexpression of a CAP1 mutant lacking Cys29
      (and therefore, incapable of dimerization in response to Cd2+) increased RMC
      viability and provided some protection of F-actin structures against Cd2+. It is
      concluded that Cd2+ brings about disruption of the RMC cytoskeleton in part
      through formation of a CAP1 dimer that increases recruitment of cofilin to F
      actin filaments.

PMID- 29222747
TI  - Reconstructing High-Quality Large-Scale Metabolic Models with merlin.
AB  - Here, the basic principles of reconstructing genome-scale metabolic models with
      merlin are described. This tool covers the basic stages of this process,
      providing several tools that allow assembling models, using the sequenced genome
      as a starting point. merlin has two main modules, separating the process of
      annotating (enzymes, transporters, and compartments) on the genome from the
      process of model assembly, though information from the former is integrated in
      the latter after curation. Moreover, merlin provides several tools to curate the
      model, including tools for generating reactions' gene rules and placeholder
      entities for biomass precursors, such as proteins (e-protein) or nucleotides (e
      DNA and e-RNA) among others.This tutorial covers each feature of merlin in
      detail, including the assessment of experimental data for the validation of the
      model.

PMID- 29222748
TI  - Analyzing and Designing Cell Factories with OptFlux.
AB  - OptFlux was launched in 2010 as the first open-source and user-friendly platform
      containing all the major methods for performing metabolic engineering tasks in
      silico. Main features included the possibility of performing microbial strain
      simulations with widely used methods such as Flux Balance Analysis and strain
      design using Evolutionary Algorithms. Since then, OptFlux suffered a major re
      factoring to improve its efficiency and reliability, while many features were
      added in the form of novel plug-ins, such as the BioVisualizer and the over/under
      expression plug-ins. The current chapter described the main mathematical
      formulations of the major methods implemented within OptFlux, also providing a
      detailed guide on the usage of those functionalities.

PMID- 29222749
TI  - The MONGOOSE Rational Arithmetic Toolbox.
AB  - The modeling of metabolic networks has seen a rapid expansion following the
      complete sequencing of thousands of genomes. The constraint-based modeling
      framework has emerged as one of the most popular approaches to reconstructing and
      analyzing genome-scale metabolic models. Its main assumption is that of a quasi
      steady-state, requiring that the production of each internal metabolite be
      balanced by its consumption. However, due to the multiscale nature of the models,
      the large number of reactions and metabolites, and the use of floating-point
      arithmetic for the stoichiometric coefficients, ensuring that this assumption
      holds can be challenging.The MONGOOSE toolbox addresses this problem by using
      rational arithmetic, thus ensuring that models are analyzed in a reproducible
      manner and consistently with modeling assumptions. In this chapter we present a
      protocol for the complete analysis of a metabolic network model using the
      MONGOOSE toolbox, via its newly developed GUI, and describe how it can be used as
      a model-checking platform both during and after the model construction process.

PMID- 29222750
TI  - The FASTCORE Family: For the Fast Reconstruction of Compact Context-Specific
      Metabolic Networks Models.
AB  - The FASTCORE family is a family of algorithms that are mainly used to build
      context-specific models but can also be applied to other tasks such as gapfilling
      and consistency testing. The FASTCORE family has very low computational demands
      with running times that are several orders of magnitude lower than its main
      competitors. Furthermore, the models built by the FASTCORE family have a better
      resolution power (defined as the ability to capture metabolic variations between
      different tissues, cell types, or contexts) than models from other algorithms.

PMID- 29222751
TI  - Reconstruction and Analysis of Central Metabolism in Microbes.
AB  - Genome-scale metabolic models (GEMs) generated from automated reconstruction
      pipelines often lack accuracy due to the need for extensive gapfilling and the
      inference of periphery metabolic pathways based on lower-confidence annotations.
      The central carbon pathways and electron transport chains are among the most well
      understood regions of microbial metabolism, and these pathways contribute
      significantly toward defining cellular behavior and growth conditions. Thus, it
      is often useful to construct a simplified core metabolic model (CMM) that is
      comprised of only the high-confidence central pathways. In this chapter, we
      discuss methods for producing core metabolic models (CMM) based on genome
      annotations. With its reduced scope compared to GEMs, CMM reconstruction focuses
      on accurate representation of the central metabolic pathways related to energy
      biosynthesis and accurate energy yield predictions. We demonstrate the
      reconstruction and analysis of CMMs using the DOE Systems Biology Knowledgebase
      (KBase). The complete workflow is available at http://kbase.us/core-models/.

PMID- 29222752
TI  - Using PSAMM for the Curation and Analysis of Genome-Scale Metabolic Models.
AB  - PSAMM is an open source software package that supports the iterative curation and
      analysis of genome-scale models (GEMs). It aims to integrate the annotation and
      consistency checking of metabolic models with the simulation of metabolic fluxes.
      The model representation in PSAMM is compatible with version tracking systems
      like Git, which allows for full documentation of model file changes and enables
      collaborative curations of large, complex models. This chapter provides a
      protocol for using PSAMM functions and a detailed description of the various
      aspects in setting up and using PSAMM for the simulation and analysis of
      metabolic models. The overall PSAMM workflow outlined in this chapter includes
      the import and export of model files, the documentation of model modifications
      using the Git version control system, the application of consistency checking
      functions for model curations, and the numerical simulation of metabolic models.

PMID- 29222753
TI  - Integration of Comparative Genomics with Genome-Scale Metabolic Modeling to
      Investigate Strain-Specific Phenotypical Differences.
AB  - Genome-scale metabolic reconstructions are powerful resources that allow
      translation biological knowledge and genomic information to phenotypical
      predictions using a number of constraint-based methods. This approach has been
      applied in recent years to gain deep insights into the cellular phenotype role of
      the genes at a systems-level, driving the design of targeted experiments and
      paving the way for knowledge-based synthetic biology.The identification of
      genetic determinants underlying the variability at the phenotypical level is
      crucial to understand the evolutionary trajectories of a bacterial species.
      Recently, genome-scale metabolic models of different strains have been assembled
      to highlight the intra-species diversity at the metabolic level. The strain
      specific metabolic capabilities and auxotrophies can be used to identify factors
      related to the lifestyle diversity of a bacterial species.In this chapter, we
      present the computational steps to perform genome-scale metabolic modeling in the
      context of comparative genomics, and the different challenges related to this
      task.

PMID- 29222754
TI  - Template-Assisted Metabolic Reconstruction and Assembly of Hybrid Bacterial
      Models.
AB  - Intraspecific genomic exchanges happen frequently between bacteria living in the
      same natural environment and can also be performed artificially in the laboratory
      for basic research or genetic/metabolic engineering purposes. In silico metabolic
      reconstruction and simulation of the metabolism of the hybrid strains that result
      from these processes can be used to predict the phenotypic outcome of such
      genomic rearrangements; this can be especially helpful as a designing tool in the
      purview of synthetic biology. However, reconstructing the metabolism of a
      bacterium with a hybrid genome through in silico approaches is not a trivial
      task, as it requires taking into account the complex relationships existing
      between metabolic genes and how they change (or remain unchanged) when new genes
      are placed in a different genomic context. Furthermore, in order to "mix" the
      metabolic models of different bacterial strains one needs at least two different
      metabolic models to begin with, and reconstructing a genome-scale model from the
      ground up is a challenging task itself, requiring an intensive manual effort and
      a great deal of information. In this chapter, we propose two general protocols to
      address the aforementioned issues of: (1) quickly generating strain-specific
      metabolic models, given the relevant genomic sequence and an already existing,
      high-quality metabolic model of a different strain belonging to the same species,
      and (2) reconstructing the metabolic model of a hybrid strain containing genomic
      elements from two different parental strains.

PMID- 29222755
TI  - Integrated Host-Pathogen Metabolic Reconstructions.
AB  - The science and art of Genome scale metabolic network reconstructions have been
      explicitly documented in the literature for organisms across all the three
      kingdoms of life. Constraints-based models derived from such reconstructions have
      been used to assess metabolic phenotypes of their complex connections to genotype
      accurately. The problem of infectious disease is complex due to the
      multifactorial response of the host to the pathogen. Systems biology approaches
      and modeling allow one to study, understand, and predict emergent properties of
      such complex responses. The integration of the host and pathogen metabolic
      networks and the subsequent merger of their stoichiometric matrices is nontrivial
      and requires understanding of both pathogen and host metabolism and physiologies.
      The protocol here describes the detailed process of network and stoichiometric
      matrix merger using a salmonella-mouse macrophage model. The protocol also
      discusses the interfacial and objective functions required to actually embark on
      the analysis of host-pathogen interaction models.

PMID- 29222756
TI  - Metabolic Model Reconstruction and Analysis of an Artificial Microbial Ecosystem.
AB  - Microbial communities are widespread in the environment, and to isolate and
      identify species or to determine relations among microorganisms, some 'omics
      methods like metagenomics, proteomics, and metabolomics have been used. When
      combined with various 'omics data, models known as artificial microbial
      ecosystems (AME) are powerful methods that can make functional predictions about
      microbial communities. Reconstruction of an AME model is the first step for model
      analysis. Many techniques have been applied to the construction of AME models,
      e.g., the compartmentalization approach, community objectives method, and dynamic
      analysis approach. Of these approaches, species compartmentalization is the most
      relevant to genetics. Besides, some algorithms have been developed for the
      analysis of AME models. In this chapter, we present a general protocol for the
      use of the species compartmentalization method to reconstruct a model of
      microbial communities. Then, the analysis of an AME is discussed.

PMID- 29222757
TI  - RNA Sequencing and Analysis in Microorganisms for Metabolic Network
      Reconstruction.
AB  - There is a strict interplay between metabolic networks and transcriptional
      regulation in bacteria; indeed, the transcriptome regulation, affecting the
      expression of large gene sets, can be used to predict the likely "on" or "off"
      state of metabolic genes as a function of environmental factors. Up to date, many
      bacterial transcriptomes have been studied by RNAseq, hundreds of experiments
      have been performed, and Giga bases of sequences have been produced. All this
      transcriptional information could potentially be integrated into metabolic
      networks in order to obtain a more comprehensive view of their regulation and to
      increase their prediction power.To get high-quality transcriptomic data, to be
      integrated into metabolic networks, it is paramount to clearly know how to
      produce highly informative RNA sequencing libraries and how to manage RNA
      sequencing data.In this chapter, we will get across the main steps of an RNAseq
      experiment: from removal of ribosomal RNAs, to strand-specific library
      preparation, till data analysis and integration. We will try to share our
      experience and know-how, to give you a precise protocol to follow, and some
      useful recommendations or tips and tricks to adopt in order to go straightforward
      toward a successful RNAseq experiment.

PMID- 29222758
TI  - Differential Proteomics Based on 2D-Difference In-Gel Electrophoresis and Tandem
      Mass Spectrometry for the Elucidation of Biological Processes in Antibiotic
      Producer Bacterial Strains.
AB  - Proteomics based on 2D-Difference In Gel Electrophoresis (2D-DIGE) coupled with
      mass spectrometry (MS) procedures can be considered a "gold standard" to
      determine quantitatively and comparatively protein abundances in cell extracts
      from different biological sources/conditions according to a gel-based approach.
      In particular, 2D-DIGE is used for protein specie separation, detection, and
      relative quantification, whenever tandem MS is used to obtain peptide sequence
      information that is managed according to bioinformatic procedures to identify the
      differentially represented protein species. The proteomic results consist of a
      dynamic portray of over- and down-represented protein species that, with the
      integration of gene ontology resources, allow obtaining a comprehensive
      understanding of the complex network of molecular signaling, regulatory circuits,
      and biochemical reactions occurring in cellular contexts. For this reason,
      proteomics has been widely used for studying molecular physiology of Gram
      positive bacterial strains producing bioactive metabolites and belonging to
      actinomycete family. This highlighted the complex relationships linking overall
      regulatory processes and metabolic pathways to the biosynthesis of interesting
      bioactive molecules. In this chapter, we provide a detailed description of the
      procedures adopted to perform a differential proteomic analysis of the
      actinomycete Microbispora ATCC-PTA-5024, producing the promising NAI-107
      lantibiotic. Although each experimental proteomic procedure has to be optimized
      to face the specific molecular characteristics of the organism under
      investigation, the protocols here described have also been used with minor
      modifications for proteomic studies on other bacterial strains, including the
      actinomycetes Streptomyces coelicolor, S. ambofaciens, Amycolatopsis balhimycina,
      and the Gram-negative proteobacteria Klebsiella oxytoca and Pseudoalteromonas
      haloplanktis.

PMID- 29222759
TI  - Techniques for Large-Scale Bacterial Genome Manipulation and Characterization of
      the Mutants with Respect to In Silico Metabolic Reconstructions.
AB  - The rate at which all genes within a bacterial genome can be identified far
      exceeds the ability to characterize these genes. To assist in associating genes
      with cellular functions, a large-scale bacterial genome deletion approach can be
      employed to rapidly screen tens to thousands of genes for desired phenotypes.
      Here, we provide a detailed protocol for the generation of deletions of large
      segments of bacterial genomes that relies on the activity of a site-specific
      recombinase. In this procedure, two recombinase recognition target sequences are
      introduced into known positions of a bacterial genome through single cross-over
      plasmid integration. Subsequent expression of the site-specific recombinase
      mediates recombination between the two target sequences, resulting in the
      excision of the intervening region and its loss from the genome. We further
      illustrate how this deletion system can be readily adapted to function as a large
      scale in vivo cloning procedure, in which the region excised from the genome is
      captured as a replicative plasmid. We next provide a procedure for the metabolic
      analysis of bacterial large-scale genome deletion mutants using the Biolog
      Phenotype MicroArrayTM system. Finally, a pipeline is described, and a sample
      Matlab script is provided, for the integration of the obtained data with a draft
      metabolic reconstruction for the refinement of the reactions and gene-protein
      reaction relationships in a metabolic reconstruction.

PMID- 29222760
TI  - Computational Prediction of Synthetic Lethals in Genome-Scale Metabolic Models
      Using Fast-SL.
AB  - In this chapter, we describe Fast-SL, an in silico approach to predict synthetic
      lethals in genome-scale metabolic models. Synthetic lethals are sets of genes or
      reactions where only the simultaneous removal of all genes or reactions in the
      set abolishes growth of an organism. In silico approaches to predict synthetic
      lethals are based on Flux Balance Analysis (FBA), a popular constraint-based
      analysis method based on linear programming. FBA has been shown to accurately
      predict the viability of various genome-scale metabolic models. Fast-SL builds on
      the framework of FBA and enables the prediction of synthetic lethal reactions or
      genes in different organisms, under various environmental conditions. Predicting
      synthetic lethals in metabolic network models allows us to generate hypotheses on
      possible novel genetic interactions and potential candidates for combinatorial
      therapy, in case of pathogenic organisms. We here summarize the Fast-SL approach
      for analyzing metabolic networks and detail the procedure to predict synthetic
      lethals in any given metabolic model. We illustrate the approach by predicting
      synthetic lethals in Escherichia coli. The Fast-SL implementation for MATLAB is
      available from https://github.com/RamanLab/FastSL/ .

PMID- 29222761
TI  - Coupling Fluxes, Enzymes, and Regulation in Genome-Scale Metabolic Models.
AB  - Genome-scale models have expanded beyond their metabolic origins. Multiple
      modeling frameworks are required to combine metabolism with enzymatic networks,
      transcription, translation, and regulation. Mathematical programming offers a
      powerful set of tools for tackling these "multi-modality" models, although
      special attention must be paid to the connections between modeling types. This
      chapter reviews common methods for combining metabolic and discrete logical
      models into a single mathematical programming framework. Best practices, caveats,
      and recommendations are presented for the most commonly used software packages.
      Methods for troubleshooting large sets of logical rules are also discussed.

PMID- 29222762
TI  - Dynamic Flux Balance Analysis Using DFBAlab.
AB  - Bioprocesses are of critical importance in several industries such as the food
      and pharmaceutical industries. Despite their importance and widespread
      application, bioprocess models remain rather simplistic and based on unstructured
      models. These simple models have limitations, making it very difficult to model
      complex bioprocesses. With dynamic flux balance analysis (DFBA) more
      comprehensive bioprocess models can be obtained. DFBA simulations are difficult
      to carry out because they result in dynamic systems with linear programs
      embedded. Therefore, the use of DFBA as a modeling tool has been limited. With
      DFBAlab, a MATLAB code that performs efficient and reliable DFBA simulations, the
      use of DFBA as a modeling tool has become more accessible. Here, we illustrate
      with an example how to implement bioprocess models in DFBAlab.

PMID- 29222763
TI  - Designing Optimized Production Hosts by Metabolic Modeling.
AB  - Many of the complex and expensive production steps in the chemical industry are
      readily available in living cells. In order to overcome the metabolic limits of
      these cells, the optimal genetic intervention strategies can be computed by the
      use of metabolic modeling. Elementary flux mode analysis (EFMA) is an ideal tool
      for this task, as it does not require defining a cellular objective function. We
      present two EFMA-based methods to optimize production hosts: (1) the standard
      approach that can only be used for small and medium scale metabolic networks and
      (2) the advanced dual system approach that can be utilized to directly compute
      intervention strategies in a genome-scale metabolic model.

PMID- 29222764
TI  - Optimization of Multi-Omic Genome-Scale Models: Methodologies, Hands-on Tutorial,
      and Perspectives.
AB  - Genome-scale metabolic models are valuable tools for assessing the metabolic
      potential of living organisms. Being downstream of gene expression, metabolism is
      increasingly being used as an indicator of the phenotypic outcome for drugs and
      therapies. We here present a review of the principal methods used for constraint
      based modelling in systems biology, and explore how the integration of multi-omic
      data can be used to improve phenotypic predictions of genome-scale metabolic
      models. We believe that the large-scale comparison of the metabolic response of
      an organism to different environmental conditions will be an important challenge
      for genome-scale models. Therefore, within the context of multi-omic methods, we
      describe a tutorial for multi-objective optimization using the metabolic and
      transcriptomics adaptation estimator (METRADE), implemented in MATLAB. METRADE
      uses microarray and codon usage data to model bacterial metabolic response to
      environmental conditions (e.g., antibiotics, temperatures, heat shock). Finally,
      we discuss key considerations for the integration of multi-omic networks into
      metabolic models, towards automatically extracting knowledge from such models.

PMID- 29222765
TI  - Cancer driver G-protein coupled receptor (GPCR) induced beta-catenin nuclear
      localization: the transcriptional junction.
AB  - G protein-coupled receptors (GPCRs) comprise the main signal-transmitting
      components in the cell membrane. Over the past several years, biochemical and
      structural analyses have immensely enhanced our knowledge of GPCR involvement in
      health and disease states. The present review focuses on GPCRs that are cancer
      drivers, involved in tumor growth and development. Our aim is to highlight the
      involvement of stabilized beta-catenin molecular machinery with a specific array
      of GPCRs. We discuss recent advances in understanding the molecular path leading
      to beta-catenin nuclear localization and transcriptional activity and their
      implications for future cancer therapy research.

PMID- 29222766
TI  - Electrical velocimetry for non-invasive monitoring of the closure of the ductus
      arteriosus in preterm infants.
AB  - : Closure of a patent ductus arteriosus (PDA) in preterm infants modifies cardiac
      output and induces adaptive changes in the hemodynamic situation. The present
      study aims to analyze those changes, through a non-invasive cardiac output
      monitor based on blood electrical velocimetry, in preterm babies. A prospective
      observational study of preterm infants with a gestational age of less than 28
      weeks, and a hemodynamic significant PDA, requires intravenous ibuprofen or
      surgical closure. All patients were monitored with electrical velocimetry before
      treatment and through the following 72 h. Two groups were defined, ibuprofen and
      surgical closure. Variations of cardiac output were analyzed from the basal
      situation and at 1, 8, 24, 48, and 72 h on each group. During a 12-month period,
      18 patients were studied. The median gestational age in the ibuprofen group
      (12/18) was 26+5 weeks (25+5-27+3) with a median birth weight of 875 (670-1010)
      g. The cardiac output index (CI) value was 0.29 l/kg/min (0.24-0.34). Among the
      patients with confirmed ductus closure (50%), a significant CI decrease was shown
      (0.24 vs 0.29 l/kg/min; P 0.03) after 72 h (three ibuprofen doses). A
      statistically significant decrease in systolic volume (SVI) was found: 1.62 vs
      1.88 ml/kg, P 0.03 with a decrease in contractility (ICON), 85 vs 140, P 0.02.
      The gestational age in the surgical group (6/18) was 25+2 weeks (24-26+3) with a
      median weight of 745 (660-820) g. All patients in this group showed a decrease in
      the immediate postoperative CI (1 h after surgery) 0.24 vs 0.30 l/kg/min, P 0.05,
      and a significant decrease in contractility (ICON 77 vs 147, P 0.03). In
      addition, a no statistically significant decrease in SVI (1.54 vs 1.83 ml/kg, P
      0.06), as well as an increase in systemic vascular resistance (10,615 vs 8797
      dyn/cm2, P 0.08), were detected. This deterioration was transient without
      significant differences in the remaining periods of time evaluated. CONCLUSION:
      The surgical closure of the PDA in preterm infants causes a transient
      deterioration of cardiac function linked to a documented decrease in the left
      ventricular output. The hemodynamic changes detected after pharmacological PDA
      closure are similar but those patients present a better clinical tolerance to
      changes in the cardiac output. What is Known: * Surgical ductus closure generates
      acute hemodynamic changes in cardiac output and left ventricular function. What
      is New: * The hemodynamic changes detected after pharmacological ductus closure
      are similar to those found in the surgical closure. Electrical velocimetry can
      detect those changes.

PMID- 29222767
TI  - Platelet Counts and Liver Enzymes After Gastric Bypass Surgery.
AB  - BACKGROUND: Obesity is associated with chronic inflammation, liver steatosis and
      increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine
      aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and
      liver fat content. Increased platelet counts (PCs) are a biomarker reflecting
      inflammation and the degree of fibrosis in NAFLD. We investigated alterations in
      PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric
      bypass (RYGBP). METHODS: One hundred twenty-four morbidly obese non-diabetic
      patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP.
      RESULTS: Body mass index (BMI) was reduced from 43.5 kg/m2 (baseline) to 31.1
      kg/m2 (follow-up), and p < 0.001 and weight declined from 126.2 to 89.0 kg. PCs
      decreased from 303 * 109 to 260 * 109/l, p < 0.001. GGT was reduced from 0.63 to
      0.38 MUkat/l, p < 0.001. ALT decreased from 0.69 to 0.59 MUkat/l, p = 0.006. CRP
      was lowered from 7.3 to 5.4 mg/l p < 0.001 and ferritin from 106 to 84 MUg/l p <
      0.001. The alterations in PCs correlated with the changes in CRP (r = 0.38, p =
      0.001), BMI (r = 0.25, p = 0.012), weight (r = 0.24, p = 0.015) and inversely
      correlated with ferritin (r = 21, p = 0.036). CONCLUSIONS: PCs, GGT and ALT
      (markers for NAFLD), and CRP and ferritin (markers for inflammation) decreased in
      morbidly obese after RYGBP. The decrease in PCs correlated with alterations in
      CRP, BMI, weight and ferritin. The lowering of liver enzymes may reflect a
      lowered liver fat content and decreased general inflammation.

PMID- 29222768
TI  - Thai Norms for Name, Image, and Category Agreement, Object Familiarity, Visual
      Complexity, Manipulability, and Age of Acquisition for 480 Color Photographic
      Objects.
AB  - Normative databases containing psycholinguistic variables are commonly used to
      aid stimulus selection for investigations into language and other cognitive
      processes. Norms exist for many languages, but not for Thai. The aim of the
      present research, therefore, was to obtain Thai normative data for the BOSS, a
      set of 480 high resolution color photographic images of real objects (Brodeur et
      al. in PLoS ONE 5(5), 2010.  https://doi.org/10.1371/journal.pone.0010773 ).
      Norms were provided by 584 Thai university students on eight dimensions: name
      agreement, object familiarity, visual complexity, category agreement, image
      agreement, two types of manipulability (graspability and mimeability), and age of
      acquisition. The results revealed comparatively similar levels of name agreement
      to Brodeur et al. especially when unfamiliar items were factored out. The pattern
      of intercorrelations among the Thai psycholinguistic norms was comparable to
      previous studies and our cross-linguistic correlations were robust for the same
      set of pictures in English and French. Conjointly, the findings extend the
      relevancy of the BOSS to Thailand, supporting this photographic resource for
      investigations of language and other cognitive processes in monolingual,
      multilingual, and brain-impaired populations.

PMID- 29222769
TI  - Neurotrophic Factors: An Overview.
AB  - The neurotrophins are a family of closely related proteins that were first
      identified as survival factors for sympathetic and sensory neurons and have since
      been shown to control a number of aspects of survival, development, and function
      of neurons in both the central and peripheral nervous systems. Limiting
      quantities of neurotrophins during development control the numbers of surviving
      neurons to ensure a match between neurons and the requirement for a suitable
      density of target innervation. Biological effects of each of the four mammalian
      neurotrophins are mediated through activation of one or more of the three members
      of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases
      (TrkA, TrkB, and TrkC). In addition, all neurotrophins activate the p75
      neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor
      superfamily. Neurotrophin engagement of Trk receptors leads to activation of Ras,
      phosphatidylinositol 3-kinase, phospholipase C-gamma1, and signaling pathways
      controlled through these proteins, including the mitogen-activated protein
      kinases. Neurotrophin availability is required into adulthood, where they control
      synaptic function and plasticity and sustain neuronal cell survival, morphology,
      and differentiation. This article will provide an overview of neurotrophin
      biology, their receptors, and signaling pathways.

PMID- 29222770
TI  - Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to
      Investigate NGF Neuroprotective and Reparative Actions.
AB  - The eye is a central nervous system structure that is uniquely accessible to
      local treatment. Through the ocular surface, it is possible to access the retina,
      optic nerve, and brain. Animal models of retina degeneration or optic nerve crush
      could thus serve as tools to investigate whether and how factors, which are
      anterogradely or retrogradely transported through the optic nerve, might
      contribute to activate neuroprotection and eventually regeneration. Among these
      factors, nerve growth factor (NGF) plays a crucial role during development of the
      visual system, as well as during the entire life span, and in pathological
      conditions. The ability of NGF to exert survival and trophic actions on the
      retina and brain cells when applied intraocularly and topically as eye drops is
      critically reviewed here, together with the effects of ocular neurotrophins on
      neuronal pathways influencing body rhythm, cognitions, and behavioral functions.
      The latest data from animal models and humans are presented, and the mechanism of
      action of ocularly administered NGF is discussed. NGF eye drops are proposed as
      an experimental strategy to investigate the role and cellular targets of
      neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and
      their involvement in the regulation of neurological and behavioral dysfunctions.

PMID- 29222771
TI  - Culture of Rodent Cortical, Hippocampal, and Striatal Neurons.
AB  - Neurons cultured from rodent central nervous system tissues represent important
      tools in the study of neurodegenerative disease mechanisms and neuroregenerative
      processes, including the survival- and axon growth-promoting properties of
      neurotrophic factors. This chapter presents a detailed protocol for the
      preparation of rat and mouse cortical, hippocampal, and striatal neuron cell
      cultures, using either embryonic or postnatal tissue with enzymatic digestion.

PMID- 29222772
TI  - Culture of Neonatal Rodent Microglia, Astrocytes, and Oligodendrocytes from the
      Cortex, Spinal Cord, and Cerebellum.
AB  - The protocol described in this chapter covers the preparation and culture of
      enriched populations of microglia, astrocytes, and oligodendrocytes from the
      cortex and spinal cord of neonatal rat and mouse. The procedure is based on
      enzymatic digestion of the tissue, followed by the culture of a mixed glial cell
      population which is then utilized as the starting point for the isolation, via
      differential attachment, of the different cell types.

PMID- 29222773
TI  - Central Nervous System Neuron-Glia co-Culture Models and Application to
      Neuroprotective Agents.
AB  - Glial cell activation plays an important role in the pathogenesis of various
      neurodegenerative disorders. This article presents a protocol for the preparation
      of cultures consisting of rat embryonic cortical neurons grown in the presence of
      cortical microglia, in which the glia are present in physical contact with the
      neurons or separated by a semipermeable membrane barrier. An example of how such
      systems can be used to evaluate potential neuroprotective agents will also be
      described.

PMID- 29222774
TI  - Preparation of Adult Rat Sensory Neuron Cultures and Their Application to Growth
      Cone Turning Assays.
AB  - The directional trajectory of growing peripheral nerve axons in the adult impacts
      their successful regeneration to denervated target tissues. Misdirected axons in
      neuromas, injured nerve trunks, or nerves with attempted repair diminish the
      success of regeneration. The behavior of adult rodent peripheral sensory neurons
      in vitro, in turn, is helpful in predicting axonal behavior in vivo. Here, we
      describe the adaptation of embryonic neuron growth cone turning assays, an
      important technique in developmental neurobiology, to adult rat sensory neurons.
      With some key modifications, and selection of subtypes of neurons likely to
      respond to a purported growth factor, short-term responses to molecular gradients
      can be analyzed using routine dorsal root ganglion neuronal cell culture
      techniques. The caveats are that short-term turning does not necessarily reflect
      on the overall tropic impact of a molecule, particularly if it alters growth
      cones through intra-axonal translation. Similarly, to understand the trajectory
      of an axon, it must be in a growth mode, such as that associated with
      preconditioning from previous injury.

PMID- 29222775
TI  - Sensory Neurons from Tau Transgenic Mice and Their Utility in Drug Screening.
AB  - Tau misfolding is a major cause of neurodegeneration, tauopathies being a growing
      group of diseases in which tau forms insoluble aggregates, best known in
      Alzheimer disease as neurofibrillary tangles (NFTs). Many transgenic mouse models
      of tauopathies have been generated, but it has been difficult to demonstrate
      disease in primary brain neurons from these mice because neurons need to be
      harvested within a few days of birth and tau fails to produce NFTs. Transgenic
      mice have been generated that express the 0N4R isoform of human tau mutated at
      amino acid 301 (P301S mice) under the Thy1.2 promoter. These mice, which model an
      inherited form of frontotemporal dementia, develop NFTs around 5 months of age.
      Taking advantage of the fact that Thy1.2 is expressed in the peripheral nervous
      system, we found that dorsal root ganglion (DRG) neurons express P301S tau and
      develop tau pathology along a similar time course to that found in central
      nervous system neurons in mice. Thus, NFTs are well-developed around 5 months of
      age. Because DRG neurons can be cultured from adult mice for months, they have
      proven to be an excellent model for studying how tau pathology develops and for
      screening compounds that may ameliorate tau pathology. Here we present a detailed
      protocol for the preparation of long-term DRG neuron cultures and describe how to
      study whether activation of autophagy ameliorates tau pathology.

PMID- 29222776
TI  - Culture of Rat Mesencephalic Dopaminergic Neurons and Application to Neurotoxic
      and Neuroprotective Agents.
AB  - Dopaminergic neuronal cell degeneration is the principal characteristic feature
      of the neuropathology of Parkinson disease. Cultures of mesencephalic neurons are
      widely used as a source of dopaminergic neurons for the study of mechanisms
      implicated in dopaminergic cell death and for the evaluation of potential
      dopaminergic neuroprotective agents, including neurotrophic factors. This chapter
      presents a detailed protocol for the preparation of rat mesencephalic cell
      cultures and their application to evaluating the effect of the dopaminergic
      neurotoxin 1-methyl-4-phenylpyridinium and the neuroprotective action of brain
      derived neurotrophic factor.

PMID- 29222777
TI  - Culture of Neurons and Smooth Muscle Cells from the Myenteric Plexus of Adult
      Mice.
AB  - In the enteric nervous system, neurons make contact with smooth muscle cells to
      regulate gastrointestinal functions. Since neuronal cell alterations and
      intestinal motor dysfunctions are strictly linked, in vitro models based on the
      culture of neurons or smooth muscle cells are of great advantage to elucidate the
      functions of the enteric nervous system under physiological and pathological
      conditions. In this chapter, we provide the protocol for isolation of neurons and
      smooth muscle cells from the myenteric plexus of adult mice. The isolated cells
      are suitable for immunocytochemical applications or electrophysiological
      investigations and/or co-culturing experiments.

PMID- 29222778
TI  - Astrocyte/Microglia Cocultures as a Model to Study Neuroinflammation.
AB  - Glial cell activation plays an important role in the pathogenesis of various
      neurodegenerative disorders as well as in chronic and neuropathic pain. This
      chapter describes a model which allows one to assess the individual and combined
      contributions of astrocytes and microglia in response to a pro-inflammatory
      stimulus, with emphasis on ionotropic purinergic receptors.

PMID- 29222779
TI  - Micropatterned Geometry Shape Oligodendrocyte and Microglia Plasticity.
AB  - Cellular adhesion is essential in maintaining multicellular structure by
      connecting cells to each other in vivo and to a biomimetic substrate in vitro. In
      this context, one of the first steps toward the comprehension, for instance, of
      oligodendrocyte and microglia adhesion and migrating behavior consists in
      discriminating the different morphological features that can be acquired when
      cells are cultured on diverse surface topographies that mimic an in vivo three
      dimensional environment. With this in mind, in this chapter, we describe how to
      exploit the silicon isotropic topography consisting of line-grating geometries
      and micropillar structures fabricated on polydimethylsiloxane by soft
      lithography. By reproducing a specialized niche for the cells, micropatterned
      biomimetic substrates can help to understand the role of structural determinants
      in priming morphogenesis of oligodendrocytes and microglia and can be exploited
      for translational research on functional tissue engineering and implantable
      device design.

PMID- 29222780
TI  - Oligodendrocyte Progenitor Cell Cultures: A Model to Screen Neurotrophic
      Compounds for Myelin Repair.
AB  - The protocol presented in this chapter covers the application of rat cortical
      oligodendrocyte progenitor cells cultured under conditions of differentiation for
      the evaluation of agents with potential trophic activity, that is, which are
      capable of promoting maturation under such conditions. As an example we have
      chosen a co-ultramicronized N-palmitoylethanolamine/luteolin composite, a
      formulation described in the literature as possessing anti-inflammatory,
      neuroprotective, and neuroregenerative actions.

PMID- 29222781
TI  - Cell Enumeration Assays: Application of the MTT and Sulforhodamine B Assays to
      Lipopolysaccharide-Stimulated Neonatal Rodent Microglia.
AB  - Glial cell activation, in particular microglia, plays an important role in the
      pathogenesis of various neurodegenerative disorders as well as in chronic and
      neuropathic pain. This chapter compares two established cell enumeration assays,
      namely, the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide assay and the protein-binding sulforhodamine B assay for microglia as a
      function of culture condition and activation state. The pros and cons of each are
      then described.

PMID- 29222782
TI  - Diolistic Labeling and Analysis of Dendritic Spines.
AB  - Dendritic spines are diverse and plastic components of the neuronal cell
      apparatus and are highly responsive to trophic factors during both development
      and adulthood. Diolistic labeling of neurons with lipophilic fluorescent dyes,
      coupled with advanced high-resolution microscopy methods, provides robust
      labeling of dendritic spines for assessment of their density and morphology.
      Here, we describe a method for labeling of dendritic spines using diolistic
      labeling in ex vivo brain slices, visualization using confocal laser scanning
      microscopy, deconvolution, and analysis using the Surpass module of Bitplane
      Imaris software.

PMID- 29222783
TI  - Culture of Mouse Giant Central Nervous System Synapses and Application for
      Imaging and Electrophysiological Analyses.
AB  - Primary neuronal cell culture preparations are widely used to investigate
      synaptic functions. This chapter describes a detailed protocol for the
      preparation of a neuronal cell culture in which giant calyx-type synaptic
      terminals are formed. This chapter also presents detailed protocols for utilizing
      the main technical advantages provided by such a preparation, namely, labeling
      and imaging of synaptic organelles and electrophysiological recordings directly
      from presynaptic terminals.

PMID- 29222784
TI  - Methods for Quantitative Analysis of Axonal Cargo Transport.
AB  - Neurons rely on complex axonal transport mechanisms that mediate the
      intracellular dynamics of proteins, vesicles, and mitochondria along their high
      polarized structure. The fast improvement of live imaging techniques of
      fluorescent cargos allowed the identification of the diverse motion properties of
      different transported molecules. These properties arise as the result of
      molecular interactions between many players involved in axonal transport. Motor
      proteins, microtubule tracks, cargo association, and even axonal viscosity
      contribute to the proper axonal dynamics of different cargos. The unique
      properties in each cargo determine their distribution and location that is
      relevant to ensure neuronal cell activity and survival. This chapter provides a
      computational-based method for the generation of cargo trajectories and the
      identification of different motion regimes while cargo moves along axons. Then,
      the procedure to extract relevant parameters from active, diffusive, and confined
      motion is provided. These properties will allow a better comprehension of the
      nature and characteristics of cargo motion in living cells, therefore
      contributing to understanding the consequences of transport defects that arise
      during diseases of the nervous system.

PMID- 29222785
TI  - Neuronal Cell Morphology in Primary Cerebellar Granule Cells Using High-Content
      Analysis.
AB  - Neurite outgrowth, one of the underlying cellular processes that defines the
      development and functionality of the mammalian nervous system, is also a
      sensitive indicator of neuronal cell health. From screening libraries of putative
      neurotherapeutic compounds to analyzing the millions of environmental pollutants
      for which we have inadequate neurotoxicity safety data, the large volume of
      chemical compounds that require evaluation is a major obstacle for manual imaging
      and analysis methods. In this context, high-content analysis (HCA) has emerged as
      a sensitive and accurate method for detecting changes in neuronal cell morphology
      within a format applicable to screening large chemical libraries. Advances in HCA
      technologies have enabled the automated imaging and quantitative analysis of
      neurite outgrowth morphology within a 96-well plate in less than 5 min.
      Traditionally, neurite outgrowth assessment has been conducted on immortalized
      cell lines such as pheochromocytoma (PC-12) cells that differentiate into neuron
      like cells upon culture with nerve growth factor. Unfortunately, they do not
      retain all the in vivo characteristics of physiological neuronal tissue,
      including lack of synapse formation. As researchers refine neurite outgrowth
      quantitative analysis using HCA, an emerging question is how to quantify this
      biology in more complex models that more faithfully recapitulate in vivo
      environments. Primary neurons provide several benefits relative to neuronal cell
      lines, including the elaboration of axons from secondary dendrites and formation
      of both pre- and postsynaptic junctions. This chapter reviews techniques for
      evaluating neurite outgrowth using the ArrayScan HCA platform within a model
      system of primary cultures of rodent cerebellar granule cells.

PMID- 29222786
TI  - Nerve Growth Factor-Induced Angiogenesis: 1. Endothelial Cell Tube Formation
      Assay.
AB  - Nerve growth factor (NGF) is a neurotrophin promoting survival, proliferation,
      differentiation, and neuroprotection in the embryonal and adult nervous system.
      NGF also induces angiogenic effects in the cardiovascular system, which may be
      beneficial in engineering new blood vessels and for developing novel anti
      angiogenesis therapies for cancer. Angiogenesis is a cellular process
      characterized by a number of events, including endothelial cell migration,
      invasion, and assembly into capillaries. In vitro endothelial tube formation
      assays are performed using primary human umbilical vein endothelial cells, human
      aortic endothelial cells, and other human or rodent primary endothelial cells
      isolated from the vasculature of both tumors and normal tissues. Immortalized
      endothelial cell lines are also used for these assays. When seeded onto Matrigel,
      these cells reorganize to create tubelike structure, which may be used as models
      for studying some aspects of in vitro angiogenesis. Image acquisition by light
      and fluorescence microscopy and/or quantification of fluorescently labeled cells
      can be carried out manually or digitally, using commercial software and automated
      image processing. Here we detail materials, procedure, assay conditions, and cell
      labeling for quantification of endothelial cell tube formation. This model can be
      applied to study cellular and molecular mechanisms by which NGF or other
      neurotrophins promote angiogenesis. This model may also be useful for the
      development of potential angiogenic and/or anti-angiogenic drugs targeting NGF
      receptors.

PMID- 29222787
TI  - Nerve Growth Factor-Induced Angiogenesis: 2. The Quail Chorioallantoic Membrane
      Assay.
AB  - The avian chorioallantoic membrane (CAM) is a simple, highly vascularized
      extraembryonic membrane, which performs multiple functions during embryonic
      development. Therefore, the models of chicken and quail assays represent robust
      experimental platforms to study angiogenesis, which reflects perturbation of the
      entire vascular tree. This experimental approach, when combined with fractal
      morphometry, is sensitive to changes in vascular branching pattern and density.
      Nerve growth factor is a neurotrophin promoting angiogenesis in CAM models. Here,
      we provide a detailed protocol of the quail CAM, shell-less model, to study nerve
      growth factor effects on blood capillary sprouting. The quail CAM assay may be
      beneficial in investigations of cellular and molecular aspects of neurotrophin
      induced angiogenesis and for developing novel anti-angiogenesis and anticancer
      therapies.

PMID- 29222788
TI  - Rat Pancreatic Beta-Cell Culture.
AB  - In this chapter, we describe the methods used to culture mainly rat pancreatic
      beta cells. We consider necessary to use this approach to get more information
      about physiological, biophysical, and molecular biology characteristics of
      primary beta cells. Most of the literature published has been developed in murine
      and human beta-cell lines. However, there are many differences between tumoral
      cell lines and native cells because, in contrast to cell lines, primary cells do
      not divide. Moreover, cell lines can be in various stages of the cell cycle and
      thus have a different sensitivity to glucose, compared to primary cells. Finally,
      for these reasons, cell lines can be heterogeneous, as the primary cells are. The
      main problem in using primary beta cells is that despite that they are a majority
      within a culture they appear mixed with other kinds of pancreatic islet cells. If
      one needs to identify single cells or has an only beta-cell composition, it is
      necessary to process the sample further. For example, one may obtain an enriched
      population of beta cells using fluorescence-activated cell sorting or identify
      single cells with the reverse hemolytic plaque assay. The other problem is that
      cells change with time in culture, becoming old and losing some characteristics,
      and so must be used preferentially during the first week. The development of
      human beta-cell cultures is of importance in medicine because we hope one day to
      be able to transplant viable beta cells to patients with diabetes mellitus type
      1.

PMID- 29222789
TI  - Growth and Neurotrophic Factors in Embryonic Stem Cells.
AB  - In this chapter we illustrate protocols to investigate growth and neurotrophic
      factors in human and rodent (rat and mouse)-derived embryonic stem cells. The
      conventional two-dimensional cell monolayer system to grow embryonic stem cells
      is presented, focusing on the coating strategies also using extracellular matrix
      components. Then, different approaches for three-dimensional stem cell culture
      are presented, using hydrogels and scaffolds. Quantitative polymerase chain
      reaction, immunocytochemistry, immunoenzymatic ELISA assay, and multiparametric
      assays to quantify growth and neurotrophic factor production are presented.

PMID- 29222790
TI  - Site-Specific Direct Labeling of Neurotrophins and Their Receptors: From
      Biochemistry to Advanced Imaging Applications.
AB  - We describe here a versatile methodological platform to achieve site-directed and
      stoichiometry-controlled labeling of neurotrophins and their receptors with
      various probes, ranging from biotin to small organic dyes. This labeling method
      works in vitro on purified neurotrophins as well as in a living cell context,
      where it achieves selective labeling of surface-exposed neurotrophin receptors.
      Here, we list all experimental details of our labeling protocols, along with
      examples of the wide range of applications in which these can be used.

PMID- 29222791
TI  - Isolation and Culture of Brain Microvascular Endothelial Cells for In Vitro Blood
      Brain Barrier Studies.
AB  - The blood-brain barrier (BBB) is essential to maintain the proper
      microenvironment for brain function. Although formed by different cell types, the
      endothelial cells (ECs) of the brain microvessels provide the BBB with its
      selective permeability. To study the BBB in vitro, EC lines as well as primary
      isolated ECs have been used. In this chapter, we will provide a detailed protocol
      on how to isolate and culture primary brain microvascular endothelial cells from
      different species for use as in vitro models of the BBB. When performed properly,
      this protocol will allow one to obtain a pure culture of brain microvascular
      endothelial cells with which to analyze the effects of therapeutic and toxic
      agents on BBB functions.

PMID- 29222792
TI  - Preparation of Rat Hippocampal Organotypic Cultures and Application to Study
      Amyloid beta-Peptide Toxicity.
AB  - Hippocampal organotypic cultures constitute a very easy but delicate method
      widely used to study amyloid beta-peptide toxicity. This ex vivo technique is
      performed on tissues isolated from newborn rats. Here, we describe a protocol for
      the preparation and culture of hippocampal organotypic slices that can be
      maintained for 14-21 days and their application to the study of amyloid beta
      peptide toxicity.

PMID- 29222793
TI  - An Animal Model of Alzheimer Disease Based on the Intrahippocampal Injection of
      Amyloid beta-Peptide (1-42).
AB  - The intrahippocampal injection of amyloid beta peptide (1-42) (Abeta(1-42))
      represents one of the most useful animal models of Alzheimer disease. Since none
      of these available models fully represents the main pathological hallmarks of
      Alzheimer disease, stereotaxic Abeta(1-42) infusion provides researchers with an
      in vivo alternative paradigm. When performed by well-trained individuals, this
      model is the best-suited one for short-term studies focusing on the effects of
      Abeta(1-42) on a specific brain region or circuitry. Here, we describe all
      methodological phases of such a model.

PMID- 29222794
TI  - Active Induction of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.
AB  - The protocol in this chapter presents a method to actively induce experimental
      autoimmune encephalomyelitis (EAE), one of the most widely used animal models to
      study efficacy of potential drugs for treatment of multiple sclerosis. Multiple
      sclerosis is an inflammatory, demyelinating disease of the central nervous system
      and the most common cause of chronic neurological impairment in young people. In
      this model EAE is induced in female C57BL/6 mice by immunization with an emulsion
      of myelin oligodendrocyte glycoprotein (fragment 35-55) in complete Freund's
      adjuvant, followed by administration of pertussis toxin in phosphate-buffered
      saline. EAE is evidenced by ascending flaccid paralysis with inflammation
      targeting the spinal cord.

PMID- 29222795
TI  - A Model of Systemic Inflammation to Study Neuroinflammation.
AB  - Increasing evidence suggests that neurodegeneration occurs in part because the
      environment is affected during disease in a cascade of processes collectively
      termed neuroinflammation. This is a reactive response of the central nervous
      system against noxious elements that interfere with tissue homeostasis.
      Neuroinflammation is mediated by inflammatory molecules released by microglial
      cells. Understanding and controlling interactions between the immune system and
      microglial activation might represent the key to prevent or delay the onset of
      central nervous system diseases. This chapter details techniques to generate and
      characterize an in vivo model of neuroinflammation based on a single
      intraperitoneal injection of lipopolysaccharide, which can be used to understand
      the wide variety of cellular and molecular mechanisms of neuroinflammation, as
      well as to identify new therapies by testing the anti-inflammatory properties of
      synthetic and natural molecules.

PMID- 29222796
TI  - Spared Nerve Injury as a Long-Lasting Model of Neuropathic Pain.
AB  - This chapter describes surgical procedures for the induction of neuropathic pain
      using an animal model (rat or mouse) of spared nerve injury. In addition to
      technical details of the surgical technique, details of anesthesia and
      perioperative care are also included.

PMID- 29222797
TI  - An In Vivo Compression Model of Spinal Cord Injury.
AB  - Animal spinal cord injury (SCI) models have proven highly useful for
      investigating the mechanisms involved in the injury process and evaluating the
      effectiveness of experimental therapeutic interventions. Over the last years,
      substantial improvements have been made in producing consistent and reproducible
      animal SCI models. Different SCI models have been developed to address the
      mechanism of injury, being divided into contusion, compression, distraction,
      dislocation, transection, or chemical models. The method described here is a
      mouse compression model of SCI that, in many respects, faithfully reproduces SCI
      in man.

PMID- 29222798
TI  - A Controlled Cortical Impact Preclinical Model of Traumatic Brain Injury.
AB  - Over the past three decades, attempts at understanding the multifaceted
      mechanisms underlying the pathophysiology of traumatic brain injury (TBI) have
      seen the development of numerous animal models to investigate changes in
      molecular and cellular pathways and neurobehavioral outcomes. Until now,
      controlled cortical impact (CCI) represents the most frequently used mechanical
      model to induce TBI, given its accuracy, easy of control, and, most importantly,
      its ability to produce brain injuries similar to those seen in humans. The CCI
      model is based on the use of an impact system that delivers a physical impact to
      the exposed dura of an animal. This chapter will describe in detail the
      electromagnetic CCI model of TBI in mice.

PMID- 29222799
TI  - Middle Cerebral Artery Occlusion by an Intraluminal Suture Method.
AB  - Stroke represents the most common fatal neurological disease especially in highly
      developed countries. Even today, treatment options are very limited. The
      development of new therapeutic approaches replies, to a great extent, on
      experimental rodent models of focal cerebral ischemia. Since ~80% of ischemic
      strokes occur in the area of middle cerebral artery (MCA), a number of these
      stroke models are based on this artery. The intraluminal monofilament model of
      MCA occlusion involves the insertion of a surgical filament inside the external
      carotid artery and its extension into the internal carotid artery until the tip
      occludes the source of the MCA-thus arresting blood flow with resultant
      infarction in the MCA area. This technique can be utilized to model both
      permanent and transient occlusions. A major advantage of this technique is that
      it does not require craniectomy, which may affect intracranial pressure and
      temperature. Although the restored blood flow is unlike the pathophysiology of
      spontaneous human stroke, it more closely mimics the therapeutic state of
      mechanical thrombectomy which is increasingly being applied to patients with
      stroke.

PMID- 29222800
TI  - Primary Motor Neuron Culture to Promote Cellular Viability and Myelination.
AB  - A culture system that can recapitulate myelination in vitro will not only help us
      to better understand the mechanism of myelination and demyelination but also
      identify possible therapeutic interventions for treating demyelinating diseases.
      Here, we introduce a simple and reproducible myelination culture system using
      mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are
      plated on a feeder layer of SCs, which interact with and wrap around the axons of
      MNs as they differentiate in culture. In our MN-SC co-culture system, MNs survive
      over 3 weeks and extend long axons. Both viability and axon growth of MNs in the
      co-culture are markedly enhanced as compared to those of MN monocultures. Co
      labeling of myelin basic proteins and neuronal cell microtubules reveals that SCs
      form myelin sheaths by wrapping around the axons of MNs.

PMID- 29222801
TI  - Culture of Human Primary Bone Cells and Phenotype Assessment.
AB  - Bone engineering scaffolds and biomimetic substitutes are currently the leading
      techniques to repair and regenerate bone defects. Ideally, bone grafts should
      imitate the structure and properties of bone extracellular matrix, house
      osteoprogenitor cells, and provide all the necessary environmental cues to
      orchestrate the functions of osteoblast and osteoclast cells. Consequently, there
      is an increasing demand for preclinical models based on in vitro bone-derived
      cell cultures for screening of novel biomaterials. In this chapter, we provide
      the protocols for culture of primary human bone cells from explants of cortical
      mandible bone and for characterization of cell behavior on biomimetic surfaces in
      terms of strength of adhesion, proliferation, differentiation, and matrix
      mineralization.

PMID- 29222802
TI  - Recreating Intestinal Peristalsis in the Petri Dish.
AB  - Here we describe a culture technique of cells dissociated from the external
      muscularis of the guinea pig small intestine, which allows us to maintain all the
      elements involved in the intestinal peristaltic reflex. After a few days in
      culture, these cells reorganize to form a small group of cells that permit the
      generation of pacemaker activity, spontaneous contractions, and the development
      of inhibitory and excitatory junction potentials in the petri dish, all elements
      involved in the peristaltic reflex. Therefore, these co-cultures are suitable to
      study the cellular and molecular aspects related to the development, maintenance,
      and modulation of motor intestinal functions.

PMID- 29222803
TI  - Synthesis of Biocompatible Titanate Nanofibers for Effective Delivery of
      Neuroprotective Agents.
AB  - Nanoscience provides us with new opportunities to develop nanotechnologies for
      treating, in particular, central nervous system disorders such as Alzheimer
      disease and multiple sclerosis. From a methodological point of view, it is
      challenging to deliver drugs effectively across the blood-brain barrier and blood
      cerebrospinal fluid barrier. Our 10-year data and reports from both in vivo and
      in vitro studies, however, have consistently proved that therapeutic drugs of
      different types can be generally loaded in/on the nanocarriers for targeted and
      programmable deliveries to the central nervous system with a high degree of
      efficacy. This chapter presents a protocol for the synthesis of biocompatible
      titanate nanofibers as low-cost drug delivery cargos. In addition, a procedure
      for loading the neuroprotective agent Cerebrolysin onto the nanofibers is briefly
      described. Finally, experimental observations on the use of nanodrug delivery for
      superior neuroprotective effects of Cerebrolysin in traumatic brain injury are
      given as a proof of concept as compared to normal drug alone.

PMID- 29222804
TI  - Preparation and Characterization of Biocompatible Chitosan Nanoparticles for
      Targeted Brain Delivery of Peptides.
AB  - Here, we describe a nanocarrier system that can transfer chitosan nanoparticles
      loaded with either small peptides such as the caspase inhibitor Z-DEVD-FMK or a
      large peptide like basic fibroblast growth factor across the blood-brain barrier.
      The nanoparticles are selectively directed to the brain and are not measurably
      taken up by the liver and spleen. Intravital fluorescent microscopy provides an
      opportunity to study the penetration kinetics of nanoparticles loaded with
      fluorescent agents such as Nile red. Nanoparticles functionalized with anti
      transferrin antibody and loaded with peptides efficiently provided
      neuroprotection when systemically administered either as a formulation bearing a
      single peptide or a mixture of them. Failure of brain permeation of the
      nanoparticles after inhibition of vesicular transcytosis by imatinib as well as
      when nanoparticles were not functionalized with anti-transferrin antibody
      indicates that this nanomedicine formulation is rapidly transported across the
      blood-brain barrier by receptor-mediated transcytosis.

PMID- 29222805
TI  - The present and future of the Japan Society for the Promotion of Science Alumni
      Association in Australia (JSPSAAA).

PMID- 29222806
TI  - Identification of UDP-glucose binding site in glycosyltransferase domain of
      sucrose phosphate synthase from sugarcane (Saccharum officinarum) by structure
      based site-directed mutagenesis.
AB  - Sucrose phosphate synthase (SPS) is believed to be the key enzyme for controlling
      the biosynthesis of sucrose. SPSs consist of a functional glycosyltransferase
      domain that shares conserved residues with the glycosyltransferase domain of
      sucrose biosynthesis-related protein. The formation of sucrose-6-phosphate is
      catalyzed by SPS with the transfer of a glycosyl group of uridine diphosphate
      glucose (UDP-G) as an activated donor sugar to a fructose-6-phosphate as a sugar
      acceptor. However, understanding of the mechanism of catalytic and substrate
      binding in SPS is very limited. Based on amino acid sequence alignments with
      several enzymes that belong to the glycosyltransferase family, the UDP-G binding
      sites that might be critical for catalytic mechanism were identified. Here, we
      report that single point mutation of R496, D498, and V570 located in the proposed
      UDP-G binding site led to less active or complete loss of enzyme activity.
      Through structure-based site-directed mutagenesis and biochemical studies, the
      results indicated that these residues contribute to the catalytic activity of
      plant SPS. Moreover, understanding of the UDP-G binding site provides an insight
      into new strategies for enzyme engineering and redesigning a catalytic mechanism
      for UDP.

PMID- 29222807
TI  - Long non-coding RNA expression in bladder cancer.
AB  - The advent of novel high-throughput sequencing methods has facilitated
      identification of non-coding RNAs with fundamental roles in cellular biological
      and pathological conditions. A group of these consisting of at least 200
      nucleotides are called long non-coding RNAs (lncRNAs). Their participation in the
      pathogenesis of cancer has been highlighted in recent years. Bladder cancer, one
      of the most prevalent cancers worldwide, exhibits altered expression levels of
      several lncRNAs. Several in vitro and in vivo studies have assessed the effects
      of silencing RNAs on cancer cell phenotypes and in vivo tumor growth. For
      instance, in vitro studies have shown that nuclear paraspeckle assembly
      transcript 1 (NEAT1), promoter of CDKN1A antisense DNA damage-activated
      RNA(PANDAR) and metastasis-associated lung adenocarcinoma transcript 1(MALAT1)
      have oncogenic effects while Maternally expressed 3 (MEG3) and BRAF activated non
      coding RNA (BANCR) are tumor suppressors. Analysis of these data will help to
      identify a panel of lncRNAs that can be potentially used for both early detection
      and prognosis in bladder cancer patients. Here, we review the roles of several
      lncRNAs in the oncogenesis, tumor suppression, early detection, and prognosis of
      bladder cancer.

PMID- 29222809
TI  - Effect of abutment height on interproximal implant bone level in the early
      healing: A randomized clinical trial.
AB  - OBJECTIVE: The aim of this randomized clinical trial was to compare the effect on
      the interproximal implant bone loss (IBL) of two different heights (1 and 3 mm)
      of definitive abutments placed at bone level implants with a platform switched
      design. MATERIAL AND METHODS: Twenty-two patients received forty-four implants
      (6.5-10 mm length and 3.5-4 mm diameter) to replace at least two adjacent missing
      teeth, one bridge set to each patient-two implants per bridge. Patients were
      randomly allocated, and two different abutment heights, 1 and 3 mm using only one
      abutment height per bridge, were used. Clinical and radiological measurements
      were performed at 3 and 6 months after surgery. Interproximal bone level changes
      were compared between treatment groups. The association between IBL and
      categorical variables (history of periodontitis, smoking, implant location,
      implant diameter, implant length, insertion torque, width of keratinized mucosa,
      bone density, gingival biotype and antagonist) was also performed. RESULTS: At 3
      months, implants with a 1-mm abutment had significantly greater IBL (0.83 +/-
      0.19 mm) compared to implants with a 3-mm abutment (0.14 +/- 0.08 mm). At 6
      months, a greater IBL was observed at implants with 1-mm abutments compared to
      implants with 3-mm abutments (0.91 +/- 0.19 vs. 0.11 +/- 0.09 mm). The analysis
      of the relation between patient characteristics and clinical variables with IBL
      revealed no significant differences at any moment except for smoking.
      CONCLUSIONS: Abutment height is an important factor to maintain interproximal
      implant bone level in early healing. Short abutments led to a greater
      interproximal bone loss in comparison with long abutments after 6 months. Other
      variables except smoking showed no relation with interproximal bone loss in early
      healing.

PMID- 29222808
TI  - "Just a spoonful of sugar...": import of sialic acid across bacterial cell
      membranes.
AB  - Eukaryotic cell surfaces are decorated with a complex array of glycoconjugates
      that are usually capped with sialic acids, a large family of over 50 structurally
      distinct nine-carbon amino sugars, the most common member of which is N
      acetylneuraminic acid. Once made available through the action of neuraminidases,
      bacterial pathogens and commensals utilise host-derived sialic acid by degrading
      it for energy or repurposing the sialic acid onto their own cell surface to
      camouflage the bacterium from the immune system. A functional sialic acid
      transporter has been shown to be essential for the uptake of sialic acid in a
      range of human bacterial pathogens and important for host colonisation and
      persistence. Here, we review the state-of-play in the field with respect to the
      molecular mechanisms by which these bio-nanomachines transport sialic acids
      across bacterial cell membranes.

PMID- 29222810
TI  - Monocytes enhance neutrophil-induced blister formation in an ex vivo model of
      bullous pemphigoid.
AB  - BACKGROUND: Lesions of bullous pemphigoid (BP), an autoimmune subepidermal
      blistering disease characterized by the presence of tissue-bound and circulating
      autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular
      infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as
      well as B and T cells have been shown to be involved in the pathogenesis of BP.
      However, their interactions with and effective role in blister formation remain
      uncertain. This study was aimed at investigating the effect of
      monocyte/neutrophil interaction on blister formation in an ex vivo BP model.
      METHODS: Skin cryosections were incubated with purified human neutrophils and
      monocytes, in the presence or absence of BP autoantibodies. Production of
      reactive oxygen species (ROS), degranulation, mediator release (neutrophil
      elastase [NE], myeloperoxidase [MPO], matrix metalloproteinase-9 [MMP-9]),
      binding of Fcgamma receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1)
      was investigated using appropriate inhibitors. Dermal-epidermal separation (DES)
      was assessed by light microscopy and quantified by Fiji software. RESULTS:
      Monocytes and neutrophils synergistically interact resulting in a significantly
      higher DES compared to either monocytes or neutrophils separately (P < .0001).
      Monocyte/neutrophil-induced DES was associated with increased ROS production and
      was dependent on adhesion and FcgammaRIII binding. Upon stimulation by the
      granule-poor fraction of monocyte supernatants, neutrophils increased their
      release of MMP-9, thereby also DES at the dermal-epidermal junction of skin
      cryosections. CONCLUSION: Our observations suggest that the interaction of cells,
      as shown here for monocytes and neutrophils, enhances mediator release resulting
      in an increased subepidermal blister formation. Thus, blocking intercellular
      cross talk promises a new therapeutic approach for blocking tissue damage in BP.

PMID- 29222811
TI  - Association of HLA-DQB1*03:03 with pityriasis rosea in Chinese patients.
AB  - BACKGROUND: The association of human leucocyte antigen (HLA) with a variety of
      diseases has been described, especially with various autoimmune diseases.
      However, there are few studies on the association between HLA and pityriasis
      rosea (PR). AIM: To investigate the relevance of HLA II alleles with the
      development of PR. METHODS: Typing for HLA-DRB1, HLA-DQA1 and HLA-DQB1 typing was
      performed in 55 patients with PR and 90 healthy controls (HCs), using sequence
      based typing (SBT) and PCR with sequence-specific primers (PCR-SSP),
      respectively. RESULTS: We found that the frequency of HLA-DQB1*03:03 was
      significantly higher in the PR compared with the HC group [P = 0.001; relative
      risk (RR) = 2.24; 95% CI 1.38-3.6], while suggestive evidence for a protective
      effect of HLA-DQB1*06:06 was observed in the study cohort (P < 0.02; RR = 0.40;
      95% CI 0.17-0.90). CONCLUSIONS: The HLA-DQB1*03:03 allele may be a susceptible
      factor in patients with PR. In addition, the association of HLA-DQB1*03:03 with
      PR suggests participation of immunity in the pathogenesis of PR.

PMID- 29222812
TI  - Spheroid-type of AL amyloid deposition associated with colonic adenocarcinoma: A
      case report with literature review.
AB  - We report a colonic adenocarcinoma associated with diffuse submucosal deposition
      of a peculiar spheroid-type amyloid identified in the colon, terminal ileum, and
      appendix. A 65-year-old woman with past medical histories of hypertension, and
      chronic obstructive pulmonary disease, presented to the emergency room with
      cramping abdominal pain and nausea. A computed tomography (CT) scan of abdomen
      showed right colonic volvulus. Emergency right hemicolectomy was performed. The
      specimen showed colonic adenocarcinoma with focal submucosal invasion (pT1)
      arising from a villotubular adenoma. A diffuse submucosal spheroid-type amyloid
      deposition (resembling corpora amylacea-like structures with Liesegang ring
      formation) was identified in the colon, ileum, and appendix. Electron microscopy
      examination of this unusual spheroidal-type material further confirmed the
      presence of amyloid fibrils. Analysis by liquid chromatography-mass spectrometry
      detected AL (lambda) type amyloidosis in this specimen. Tests for monoclonal
      gammopathy were not performed because patient consent was not obtained. In tissue
      section evaluation, however, no plasma cell neoplasm was identified. Cases with
      isolated AL amyloid deposition in the gastrointestinal tract have been reported
      rarely, and there is no case report of colonic adenocarcinoma associated with
      primary amyloid deposition in the English literature.

PMID- 29222813
TI  - RELN signaling modulates glioblastoma growth and substrate-dependent migration.
AB  - Glioblastoma (GBM) represents the most common and most malignant type of primary
      brain tumor and significantly contributes to cancer morbidity and mortality.
      Invasion into the healthy brain parenchyma is a major feature of glioblastoma
      aggressiveness. Reelin (RELN) is a large secreted extracellular matrix
      glycoprotein that regulates neuronal migration and positioning in the developing
      brain and sustains functionality in the adult brain. We here show that both RELN
      and its main downstream effector DAB1 are silenced in glioblastoma as compared to
      non-neoplastic tissue and mRNA expression is inversely correlated with malignancy
      grade. Furthermore, RELN expression is positively correlated with patient
      survival in two large, independent clinically annotated datasets. RELN silencing
      occurs via promoter hypermethylation as shown by both database mining and
      bisulfite sequencing of the RELN promoter. Consequently, treatment with 5'
      Azacytidine and trichostatin A induced RELN expression in vitro. On the
      functional level, we found RELN to regulate glioblastoma cell migration both in a
      DAB1 (tyrosine phosphorylation)-dependent and -independent fashion, depending on
      the substrate provided. Moreover, stimulation of RELN signaling strongly reduced
      proliferation in glioblastoma cells. This phenotype depends on DAB1 stimulation
      by RELN, as a mutant that lacks all RELN induced tyrosine phosphorylation sites
      (DAB1-5F) failed to induce a growth arrest. Proteomic analyzes revealed that
      these effects are mediated by a reduction in E2F targets and dephosphorylation of
      ERK1/2. Taken together, our data establish a relevance of RELN signaling in
      glioblastoma pathology and thereby might unearth novel, yet unrecognized
      treatment options.

PMID- 29222814
TI  - SIENA-XL for improving the assessment of gray and white matter volume changes on
      brain MRI.
AB  - In this article, SIENA-XL, a new segmentation-based longitudinal pipeline is
      introduced, for: (i) increasing the precision of longitudinal volume change
      estimation for white (WM) and gray (GM) matter separately, compared with cross
      sectional segmentation methods such as SIENAX; and (ii) avoiding potential biases
      in registration-based methods when Jacobians are used, with a smoothing extent
      larger than spatial scale between tissue-interfaces, which is where atrophy
      usually occurs. SIENA-XL implements a new brain extraction procedure and a multi
      time-point intensity equalization step before performing the final segmentation
      that also includes separate segmentation of deep GM structures by using FMRIB's
      Integrated Registration and Segmentation Tool. The detection of GM and WM volume
      changes with SIENA-XL was evaluated using different healthy control (HC) and
      multiple sclerosis (MS) MRI datasets and compared with the traditional SIENAX and
      two Jacobian-based approaches, SPM12 and SIENAX-JI (a version of SIENAX including
      Jacobian integration - JI). In scan-rescan data from HCs, SIENA-XL showed: (i) a
      significant decrease in error, of 50-70% when compared with SIENAX; (ii) no
      significant differences in error when compared with SIENAX-JI and SPM12 in a scan
      rescan HC dataset that included repositioning. When tested in a HC dataset with
      scan-rescan both at baseline and after 1 year of follow-up, SIENA-XL showed: (i)
      significantly higher precision (P < 0.01) than SIENAX; (ii) no significant
      differences to SIENAX-JI and SPM12. Finally, in a dataset of 79 MS patients with
      a 2 years follow-up, SIENA-XL showed a substantial reduction of sample size, by
      comparison with SIENAX, SIENAX-JI, and SPM12, for detecting treatment effects of
      25, 30, and 50%. Hum Brain Mapp 39:1063-1077, 2018. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 29222815
TI  - Evaluation and Comparison of 2 On-Farm Tests for Estimating Somatic Cell Count in
      Quarter Milk Samples from Lactating Dairy Cattle.
AB  - BACKGROUND: The somatic cell count (SCC) is commonly used to monitor udder health
      and diagnose subclinical intramammary infection (IMI) in dairy cattle.
      HYPOTHESIS: The Somaticell test (ST) and California mastitis test (CMT) are
      clinically useful cow-side tests for diagnosing subclinical IMI. ANIMALS: One
      hundred and eleven dairy cows at dry-off and 92 cows within 4-7 days postcalving.
      METHODS: Quarter foremilk samples were obtained and analyzed with a DeLaval cell
      counter (DCC, reference method), ST, and CMT. The ST was run in a simulated cow
      side manner using milk at 37 degrees C instead of 0-8 degrees C as recommended by
      the manufacturer. Test performance for diagnosing IMI (DCC SCC >200,000 cells/mL)
      was evaluated by calculating the area under the receiver operating characteristic
      curve (AUC) and the kappa coefficient (kappa) at the optimal cut-point for each
      test. The effect of milk/reagent temperature also was evaluated. RESULTS:
      Compared to the reference method, the ST run in a simulated cow-side manner had
      an AUC = 0.68 and kappa = 0.24 at dry-off, and AUC = 0.74 and kappa = 0.40 in
      fresh cows. The CMT performed much better than the ST in diagnosing subclinical
      IMI with AUC = 0.88 and kappa = 0.77 at dry-off, and AUC = 0.87 and kappa = 0.76
      in fresh cows. The measured ST value decreased with increasing temperature of the
      milk/reagent mixture. CONCLUSIONS/CLINICAL IMPORTANCE: The ST is optimized for
      use on milk at 0-8 degrees C and is therefore designed for on-farm use on
      refrigerated milk samples. The ST is not suited for use as a cow-side screening
      test for IMI because the milk temperature exceeds the recommended range for the
      test.

PMID- 29222816
TI  - Shyness and Trajectories of Functional Network Connectivity Over Early
      Adolescence.
AB  - High shyness during early adolescence is associated with impaired peer
      relationships and risk for psychiatric disorders. Little is known, however, about
      the relation between shyness and trajectories of brain development over early
      adolescence. The current study longitudinally examined trajectories of resting
      state functional connectivity (rs-fc) within four brain networks in 147
      adolescents. Subjects underwent functional magnetic resonance imaging at three
      different time points, at average ages 10.5 (range = 7.8-13.0), 11.7 (range = 9.3
      14.1), and 12.9 years (range = 10.1-15.2). Multilevel linear modeling indicated
      that high shyness was associated with a less steep negative slope of default mode
      network (DMN) rs-fc over early adolescence relative to low shyness. Less steep
      decreases in DMN rs-fc may relate to increased self-focus in adolescents with
      high shyness.

PMID- 29222818
TI  - Task-related effective connectivity reveals that the cortical rich club gates
      cortex-wide communication.
AB  - Higher cognition may require the globally coordinated integration of specialized
      brain regions into functional networks. A collection of structural cortical hubs
      referred to as the rich club-has been hypothesized to support task-specific
      functional integration. In the present paper, we use a whole-cortex model to
      estimate directed interactions between 68 cortical regions from functional
      magnetic resonance imaging activity for four different tasks (reflecting
      different cognitive domains) and resting state. We analyze the state-dependent
      input and output effective connectivity (EC) of the structural rich club and
      relate these to whole-cortex dynamics and network reconfigurations. We find that
      the cortical rich club exhibits an increase in outgoing EC during task
      performance as compared with rest while incoming connectivity remains constant.
      Increased outgoing connectivity targets a sparse set of peripheral regions with
      specific regions strongly overlapping between tasks. At the same time, community
      detection analyses reveal massive reorganizations of interactions among
      peripheral regions, including those serving as target of increased rich club
      output. This suggests that while peripheral regions may play a role in several
      tasks, their concrete interplay might nonetheless be task-specific. Furthermore,
      we observe that whole-cortex dynamics are faster during task as compared with
      rest. The decoupling effects usually accompanying faster dynamics appear to be
      counteracted by the increased rich club outgoing EC. Together our findings speak
      to a gating mechanism of the rich club that supports fast-paced information
      exchange among relevant peripheral regions in a task-specific and goal-directed
      fashion, while constantly listening to the whole network.

PMID- 29222817
TI  - Diverse inhibitory and excitatory mechanisms shape temporal tuning in transient
      OFF alpha ganglion cells in the rabbit retina.
AB  - KEY POINTS: Neurons combine excitatory and inhibitory signals to perform
      computations. In the retina, interactions between excitation and inhibition
      enable neurons to detect specific visual features. We describe how several
      excitatory and inhibitory mechanisms work together to allow transient OFF alpha
      ganglion cells in the rabbit retina to respond selectively to high temporal
      frequencies and thus detect faster image motion. The weightings of these
      different mechanisms change with the contrast and spatiotemporal properties of
      the visual input, and thereby support temporal tuning in alpha cells over a range
      of visual conditions. The results help us understand how ganglion cells
      selectively integrate excitatory and inhibitory signals to extract specific
      information from the visual input. ABSTRACT: The 20 to 30 types of ganglion cell
      in the mammalian retina represent parallel signalling pathways that convey
      different information to the brain. alpha ganglion cells are selective for high
      temporal frequencies in visual inputs, which makes them particularly sensitive to
      rapid motion. Although alpha ganglion cells have been studied in several species,
      the synaptic basis for their selective temporal tuning remains unclear. Here, we
      analyse excitatory synaptic inputs to transient OFF alpha ganglion cells (t-OFF
      alpha GCs) in the rabbit retina. We show that convergence of excitatory and
      inhibitory synaptic inputs within the bipolar cell terminals presynaptic to the t
      OFF alpha GCs shifts the temporal tuning to higher temporal frequencies.
      GABAergic inhibition suppresses the excitatory input at low frequencies, but
      potentiates it at high frequencies. Crossover glycinergic inhibition and sodium
      channel activity in the presynaptic bipolar cells also potentiate high frequency
      excitatory inputs. We found differences in the spatial and temporal properties,
      and contrast sensitivities of these mechanisms. These differences in stimulus
      selectivity allow these mechanisms to generate bandpass temporal tuning of t-OFF
      alpha GCs over a range of visual conditions.

PMID- 29222820
TI  - Erratum.

PMID- 29222819
TI  - Benign mesothelial nodules reflux within acquired cutaneous lymphangiectasia
      associated with huge ovarian clear cell carcinoma.

PMID- 29222821
TI  - Erratum.

PMID- 29222822
TI  - Coronary microvascular dysfunction and myocardial contractile reserve in women
      with angina and no obstructive coronary artery disease.
AB  - BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of
      myocardial ischemia and may affect myocardial function at rest and during stress.
      We investigated whether CMD was associated with left ventricular diastolic and
      systolic function at rest and during pharmacologically induced hyperemic stress.
      METHODS: In a prospective cohort study, we included 963 women with angina, left
      ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram
      without significant stenosis (<50%). Parameters of left ventricular diastolic
      function, LVEF, speckle tracking-derived global longitudinal strain (GLS), and
      coronary flow velocity reserve (CFVR) were assessed by transthoracic
      echocardiography at rest and during dipyridamole stress. The GLS and LVEF
      reserves were defined as the absolute increases in GLS and LVEF during stress.
      RESULTS: Coronary flow velocity reserve (CFVR) was measured in 919 women of whom
      26% had CMD (defined as CFVR < 2). Coronary microvascular dysfunction (CMD) was
      associated with higher age and a higher resting heart rate. Women with CMD had a
      reduced GLS reserve (P = .005), while we found no association between CFVR and
      LVEF at rest, GLS at rest, or the LVEF reserve, respectively. Global longitudinal
      strain (GLS) reserve remained associated with CFVR (P = .002) in a multivariable
      regression analysis adjusted for age, hemodynamic variables, and GLS at rest. In
      age-adjusted analysis, women with low CFVR had no signs of left ventricular
      diastolic dysfunction measured by echocardiography at rest. CONCLUSION: The GLS
      reserve was significantly lower in women with CMD. The mechanisms underlying the
      association between CMD and GLS reserve warrant further study.

PMID- 29222823
TI  - Dominant role of microglial and macrophage innate immune responses in human
      ischemic infarcts.
AB  - Inflammatory mechanisms, involving granulocytes, T-cells, B-cells, macrophages
      and activated microglia, have been suggested to play a pathogenic role in
      experimental models of stroke and may be targets for therapeutic intervention.
      However, knowledge on the inflammatory response in human stroke lesions is
      limited. Here, we performed a quantitative study on the inflammatory reaction in
      human ischemic infarct lesions. We found increased numbers of T-lymphocytes,
      mainly CD8+ cells, but not of B-lymphocytes. Their number was very low in
      comparison to that seen in inflammatory diseases of the central nervous system
      and they did not show signs of activation. Polymorphonuclear leukocytes were
      present in meninges and less prominently in the perivascular space in early
      lesions, but their infiltration into the lesioned tissue was sparse with the
      exception of a single case. Microglia were lost in the necrotic core of fresh
      lesions, their number was increased in the surrounding penumbra, apparently due
      to proliferation. Using TMEM119 as a marker for the resident microglia pool,
      macrophages in lesions were in part derived from the original microglia pool,
      depending on the lesion stage. Most microglia and macrophages revealed a pro
      inflammatory activation pattern, expressing molecules involved in phagocytosis,
      oxidative injury, antigen presentation and iron metabolism and had partially lost
      the expression of P2RY12, an antigen expressed on homeostatic ("resting")
      microglia in rodents. At later lesion stages, the majority of macrophages showed
      intermediate activation patterns, expressing pro-inflammatory and anti
      inflammatory markers. Microglia in the normal white matter of controls and stroke
      patients were already partly activated toward a pro-inflammatory phenotype. Our
      data suggest that the direct contribution of lymphocytes and granulocytes to
      active tissue injury in human ischemic infarct lesions is limited and that stroke
      therapy that targets pro-inflammatory microglia and macrophage activation may be
      effective.

PMID- 29222824
TI  - Elevated levels of the antimicrobial peptide LL-37 in hidradenitis suppurativa
      are associated with a Th1/Th17 immune response.
AB  - Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly
      understood immunopathogenic mechanisms. LL-37 is an antimicrobial peptide, which
      is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous
      reports showed upregulated levels of CAMP and LL-37 in HS lesions, and therefore,
      the aim of this study was to compare levels of LL-37 in HS to other inflammatory
      skin diseases and to establish immunomodulatory functions of LL-37 in HS. We
      confirm an upregulation of the LL-37 peptide in lesional HS skin with comparable
      levels as in psoriasis patients and are able to positively correlate the presence
      of LL-37 in HS with the presence of T cells, macrophages, neutrophils, IFN-gamma,
      IL-17, IL-23, TNF-alpha, IL-32 and IL-1beta. Mechanistically, LL-37 boosts the
      proliferation of unspecifically activated CD4+ T cells via an increased calcium
      signalling independent of antigen-presenting cells. Targeting LL-37 may therefore
      represent a new therapeutic option for the treatment of this recalcitrant
      disease, but it has to be kept in mind that LL-37 also has an antimicrobial
      function.

PMID- 29222825
TI  - Outcome of sonography-based minimally invasive surgery for deep infiltrating
      endometriosis of the ureter and urinary bladder - a retrospective cohort study.
AB  - INTRODUCTION: The aim of this study was to evaluate the accuracy of transvaginal
      sonography for preoperative detection of bladder endometriosis and surgical
      outcomes regarding fertility and pain symptoms of women with urinary tract
      endometriosis. MATERIAL AND METHODS: Retrospective cohort study of consecutive
      patients with urinary tract endometriosis undergoing laparoscopic partial
      cystectomy and/or ureterolysis/decompression, ureteric resection and end-to-end
      anastomosis or ureteroneocystostomy for ureteral stenosis and hydronephrosis.
      RESULTS: Of 207 patients with deep infiltrating endometriosis, 50 exhibited
      urinary tract endometriosis, comprising 30 patients with bladder endometriosis
      and 23 women with solitary or additional hydronephrosis. Sensitivity,
      specificity, positive and negative predictive value, positive/negative likelihood
      ratios and test accuracy for transvaginal sonography detecting bladder
      endometriosis were 93%, 99%, 97%, 99%, 155.5, 0.07 and 98.6% respectively. All
      women with bladder endometriosis underwent partial cystectomy. In cases of
      hydronephrosis, 14 conservative ureterolysis/decompressions, six ureteral
      resection anastomoses and three ureteroneocystostomies were performed. Duration
      of surgery was 205 min (range 89-365 min), average blood loss was 1.6 g/dL (range
      0.3-4.6 g/dL) and hospital stay on average 8 days (range 2-16 days). The
      conversion rate was 4%. We observed five grade III complications. After a median
      follow up of 23 months, there was a decrease in dysmenorrhea (7.6-1.6; p <
      0.001), dyspareunia (3.0-0.9, p < 0.001) and dysuria (3.3-0.2; p < 0.003), and an
      increase in quality of life (3.3-8.1; p < 0.001). The overall clinical pregnancy
      rate was 46% and life birth rate 18%. CONCLUSIONS: Laparoscopic surgery for
      urinary tract endometriosis is effective for treatment of hydronephrosis,
      reduction of pain symptoms and may improve fertility. Transvaginal sonography is
      highly accurate for presurgical detection of bladder involvement.

PMID- 29222826
TI  - Application of ultra-performance liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometry in identification of three isoflavone glycosides
      and their corresponding metabolites.
AB  - RATIONALE: Metabolites of isoflavones have attracted much attention in recent
      years due to their potential bioactivities. However, the complex constituents of
      the metabolic system and the low level of metabolites make them difficult to
      analyze. A mass spectrometry (MS) method was applied in our identification of
      metabolites and study of their fragmentation pathways due to the advantages of
      rapidity, sensitivity, and low level of sample consumption. METHODS: Three
      isoflavone glycosides and their metabolites were identified using ultra
      performance liquid chromatography coupled with quadrupole time-of-flight tandem
      mass spectrometry (UPLC/QTOF-MS). These metabolites were obtained by
      anaerobically incubating three isoflavone glycosides with human intestinal flora.
      The characteristic fragments of isoflavone glycosides and their metabolites were
      used for the identification work. RESULTS: Two metabolites from ononin, three
      metabolites from irilone-4'-O-beta-D-glucoside, and five metabolites from
      sissotrin were identified respectively by the retention time (RT), accurate mass,
      and mass spectral fragmentation patterns. The losses of the glucosyl group, CO
      from the [M+H]+ ion were observed for all the three isoflavone glycosides. The
      characteristic retro-Diels-Alder (RDA) fragmentation patterns were used to
      differentiate the compounds. The metabolic pathways of the three isoflavone
      glycosides were proposed according to the identified chemical structures of the
      metabolites. CONCLUSIONS: A selective, sensitive and rapid method was established
      for detecting and identifying three isoflavone glycosides and their metabolites
      using UPLC/QTOF-MS. The established method can be used for further rapid
      structural identification studies of metabolites and natural products.
      Furthermore, the proposed metabolic pathways will be helpful for understanding
      the in vivo metabolic process of isoflavone.

PMID- 29222827
TI  - Responding to parental requests for life-sustaining treatment - relational
      potential revisited.

PMID- 29222828
TI  - Multiple gastrointestinal stromal tumors involving extragastrointestinal sites in
      neurofibromatosis type 1.

PMID- 29222829
TI  - Lichen planus in a patient treated with pembrolizumab for metastatic malignant
      melanoma.

PMID- 29222830
TI  - Dabrafenib-induced pemphigoid-like reaction.

PMID- 29222831
TI  - A review of structural brain abnormalities in Pallister-Killian syndrome.
AB  - BACKGROUND: Pallister-Killian syndrome (PKS) is a rare multisystem developmental
      syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be
      associated with neurological defects. METHODS: We describe two patients with PKS,
      one of whom has bilateral perisylvian polymicrogyria (PMG), the other with
      macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum.
      We have also summarized the current literature describing brain abnormalities in
      PKS. RESULTS: We reviewed available cases with intracranial scans (n = 93) and
      found a strong association between PKS and structural brain abnormalities
      (77.41%; 72/93). Notably, ventricular abnormalities (45.83%; 33/72),
      abnormalities of the corpus callosum (25.00%; 18/72) and cerebral atrophy
      (29.17%; 21/72) were the most frequently reported, while macrocephaly (12.5%;
      9/72) and PMG (4.17%; 3/72) were less frequent. To further understand how 12p
      genes might be relevant to brain development, we identified 63 genes which are
      enriched in the nervous system. These genes display distinct temporal as well as
      region-specific expression in the brain, suggesting specific roles in
      neurodevelopment and disease. Finally, we utilized these data to define minimal
      critical regions on 12p and their constituent genes associated with atrophy,
      abnormalities of the corpus callosum, and macrocephaly in PKS. CONCLUSION: Our
      study reinforces the association between brain abnormalities and PKS, and
      documents a diverse neurogenetic basis for structural brain abnormalities and
      impaired function in children diagnosed with this rare disorder.

PMID- 29222832
TI  - Written action plans for children with long-term conditions: A systematic review
      and synthesis of qualitative data.
AB  - BACKGROUND: Long-term conditions (LTCs) in children require a high level of self
      management. Written action plans (WAPs) have been advocated to guide decision
      making and support self-management but there is uncertainty about how WAPs "work"
      and what aspects are important for successful implementation. OBJECTIVE: To
      review and synthesize existing qualitative evidence about the design and use of
      WAPs across childhood LTCs. METHOD: We undertook a systematic search of the
      literature (Medline, EMBASE, CiNAHL, PsycInfo, Web of science) from inception to
      May 2015; critically appraised included studies; and synthesized the findings,
      drawing on normalisation process theory. RESULTS: 3473 titles were screened and
      53 papers read in full. Nine studies (four key, two minor and three of poor
      quality) contributed to our analysis, predominantly work on asthma from the USA
      and in specialist settings. WAPs may help to alleviate user worry and boost
      confidence. Confidence to act was closely linked to feelings of responsibility
      and authority. The value and use of WAPs are determined by multiple factors, and
      varies between different user groups. Logistical challenges include sharing a WAP
      between different stakeholders and keeping it up to date. Colour coding and
      pictures may enhance the appeal and usability of WAPS. CONCLUSION: WAPs are
      complex interventions but our understanding of their use and value in children
      with LTCs is limited. WAPs need to meet the needs of users who have different
      requirements/levels of understanding and confidence according to their different
      roles. Future research into WAPs needs to be both disease and context-specific.

PMID- 29222833
TI  - Association between measures of treatment quality and disease progression in
      prostate cancer radiotherapy: An exploratory analysis from the TROG 03.04 RADAR
      trial.
AB  - INTRODUCTION: Quality assurance methods are incorporated into multicentre
      radiotherapy clinical trials for ensuring consistent application of trial
      protocol and quantifying treatment uncertainties. The study's purpose was to
      determine whether post-treatment disease progression is associated with measures
      of the quality of radiotherapy treatment. METHODS: The TROG 03.04 RADAR trial
      tested the impact of androgen deprivation on prostate cancer patients receiving
      dose-escalated external beam radiation therapy. The trial incorporated a plan
      review process and Level III dosimetric intercomparison at each centre, from
      which variables suggestive of treatment quality were collected. Kaplan-Meier
      statistics and Fine and Gray competing risk modelling were employed to test for
      associations between quality-related variables and the participant outcome local
      composite progression. RESULTS: Increased 'dose-difference' at the prostatic apex
      and at the anterior rectal wall, between planned and measured dose, was
      associated with reduced progression. Participants whose treatment plans included
      clinical target volume (CTV) to planning target volume (PTV) margins exceeding
      protocol requirements also experienced reduced progression. Other quality-related
      variables, including total accrual from participating centres, measures of target
      coverage and other variations from protocol, were not significantly associated
      with progression. CONCLUSIONS: This analysis has revealed the association of
      several treatment quality factors with disease progression. Increased dose and
      dose margin coverage in the prostate region can reduce disease progression.
      Extensive and rigorous monitoring has helped to maximise treatment quality,
      reducing the incidence of quality-indicator outliers, and thus reduce the chance
      of observing significant associations with progression rates.

PMID- 29222834
TI  - Effects of a music-creation programme on the anxiety, self-esteem, and quality of
      life of people with severe mental illness: A quasi-experimental design.
AB  - Many studies have shown that music therapy improves patients' symptoms. However,
      interventions using music creation as their core await further development for
      patients with severe mental illness (SMI). The current study investigated the
      effect of a music-creation programme on the anxiety, self-esteem, and quality of
      life of patients with SMI. A quasi-experimental design using convenience sampling
      was adopted to recruit patients with SMI from a psychiatric day care centre.
      Participants were grouped based on their willingness to undergo an intervention
      (26 patients in the experimental group and 23 patients in the control group). The
      control groups participated in conventional mental rehabilitation therapy
      activities. The experimental group participated in a music-creation session for
      90 min every week over a 32-week period. The outcome indicators before and after
      the intervention were assessed using the Hamilton Anxiety Rating Scale (HAM-A),
      Rosenberg Self-Esteem Scale (RSES), and World Health Organization Quality of Life
      BREF (WHOQOL-BREF). Finally, the intervention effect was determined using
      generalized estimating equations (GEEs). After 32 weeks of intervention
      activities, the experimental group showed significant improvements in their HAM-A
      total scores (P < 0.001) and RSES total scores (P = 0.005). Regarding quality of
      life, the improvements of the experimental group in terms of the psychological (P
      = 0.016) and social relationship domains (P = 0.033) were superior to those of
      the control group. Music-creation programmes are recommended for inclusion in the
      routine rehabilitation activities of patients with SMI.

PMID- 29222835
TI  - Effective network of deep brain stimulation of subthalamic nucleus with bimodal
      positron emission tomography/functional magnetic resonance imaging in Parkinson's
      disease.
AB  - AIMS: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an
      effective treatment strategy for patients with Parkinson's disease. However, the
      biological mechanism underlying DBS treatment remains poorly understood. METHOD:
      In this study, we investigated how STN-DBS modulated the brain network using a
      bimodal positron emission tomography (PET)/functional magnetic resonance imaging
      (fMRI) dataset. We first performed an activation likelihood estimation meta
      analysis of 13 PET/SPECT studies concerning STN-DBS effects on resting-state
      brain activity in Parkinson's disease. Additionally, using a functional
      connectivity analysis in resting-state fMRI, we investigated whether these STN
      DBS-affected regions were functionally connected to constitute an effective
      network. RESULTS: The results revealed that STN-DBS reduced brain activity in the
      right thalamus, bilateral caudal supplementary area, and the left primary motor
      cortex, and it increased brain activity in the left thalamus during rest. Second,
      these STN-DBS-affected areas were functionally connected within an STN-DBS
      effective network. CONCLUSION: Deep brain stimulation of the subthalamic nucleus
      (STN-DBS) may deactivate the motor cortex as a remote and network effect,
      affecting the target and the neighboring subcortical areas. These areas may
      constitute an effective network of STN-DBS modulation. Our results shed light on
      the mechanisms of STN-DBS treatment from a network perspective and highlight the
      potential therapeutic benefits of targeted network modulation.

PMID- 29222836
TI  - Biochemical and structural insights into a thermostable cellobiohydrolase from
      Myceliophthora thermophila.
AB  - : Cellobiohydrolases hydrolyze cellulose, a linear polymer with glucose monomers
      linked exclusively by beta-1,4 glycosidic linkages. The widespread hydrogen
      bonding network tethers individual cellulose polymers forming crystalline
      cellulose, which prevent the access of hydrolytic enzymes and water molecules.
      The most abundant enzyme secreted by Myceliophthora thermophila M77 in response
      to the presence of biomass is the cellobiohydrolase MtCel7A, which is composed by
      a GH7-catalytic domain (CD), a linker, and a CBM1-type carbohydrate-binding
      module. GH7 cellobiohydrolases have been studied before, and structural models
      have been proposed. However, currently available GH7 crystal structures only
      define separate catalytic domains and/or cellulose-binding modules and do not
      include the full-length structures that are involved in shaping the catalytic
      mode of operation. In this study, we determined the 3D structure of catalytic
      domain using X-ray crystallography and retrieved the full-length enzyme envelope
      via small-angle X-ray scattering (SAXS) technique. The SAXS data reveal a tadpole
      like molecular shape with a rigid linker connecting the CD and CBM. Our
      biochemical studies show that MtCel7A has higher catalytic efficiency and
      thermostability as well as lower processivity when compared to the well-studied
      TrCel7A from Trichoderma reesei. Based on a comparison of the crystallographic
      structures of CDs and their molecular dynamic simulations, we demonstrate that
      MtCel7A has considerably higher flexibility than TrCel7A. In particular, loops
      that cover the active site are more flexible and undergo higher conformational
      fluctuations, which might account for decreased processivity and enhanced
      enzymatic efficiency. Our statistical coupling analysis suggests co-evolution of
      amino acid clusters comprising the catalytic site of MtCel7A, which correlate
      with the steps in the catalytic cycle of the enzyme. DATABASE: The atomic
      coordinates and structural factors of MtCel7A have been deposited in the Protein
      Data Bank with accession number 5W11.

PMID- 29222837
TI  - Low-melt bioactive glass-reinforced 3D printing akermanite porous cages with
      highly improved mechanical properties for lumbar spinal fusion.
AB  - Although great strides have been made in medical technology, low back/neck pain
      and intervertebral disc degeneration initiated from disc degenerative disease
      remains a clinical challenge. Within the field of regenerative medicine therapy,
      we have sought to improve the biomechanical transformation of spinal fusion
      procedures conducted using biodegradable porous implants. Specifically, we have
      focused on developing mechanically strong bioceramic cages for spinal fusion and
      functional recovery. Herein, we fabricated the akermanite (AKE) ceramic-based
      porous cages using low-melting bioactive glass (BG) and 3D printing technology.
      The osteogenic cell adhesion on the cages was evaluated in vitro, and the spinal
      fusion was tested in the intervertebral disc trauma model. The results indicated
      that incorporation of 15% or 30% BG into AKE (i.e., AKE/BG15 and AKE/BG30) could
      enhance the compressive strength of bioceramic cages by 2- or 5-fold higher than
      the pure AKE cages (AKE/BG0). In comparison with porous beta-tricalcium phosphate
      cages, the surface of AKE/BG15 and AKE/BG30 cages greatly promoted the growth and
      alkaline phosphatase expression of osteogenic cells. Histological and
      biomechanical analysis showed that the AKE/BG15 and AKE/BG30 readily stimulated
      the new bone tissue growth and improved the spinal biomechanics recovery. In the
      AKE/BG15 and AKE/BG30 cage groups, 4-6 of the rabbits demonstrated a successful
      fusion. In contrast, only 0-1 of the initial seeded AKE/BG0 and tricalcium
      phosphate cages resulted in fusion at 12 weeks post-operatively. In summary, the
      akermanite-based cages showed an increased bone regenerative effect within an
      intervertebral disc trauma model, and thus, provided a promising candidate for
      improving spinal fusion surgery.

PMID- 29222838
TI  - Results of a systematic literature review of treatment modalities for
      jugulotympanic paraganglioma, stratified per Fisch class.
AB  - OBJECTIVE: Key for successful jugulotympanic paraganglioma management is a
      personalised approach aiming for the best practice for each individual patient.
      To this end, a systematic review is performed, evaluating the local control and
      complication rates for the different treatment modalities stratified by the
      broadly accepted Fisch classification. DESIGN: A systematic literature review
      according to the PRISMA statement was performed. A detailed overview of
      individual treatment outcomes per Fisch class is provided. MAIN OUTCOME MEASURES:
      Local control, cranial nerve damage, complications, function recovery. RESULTS:
      Eighteen studies were selected, resembling 83 patients treated with radiotherapy
      and 299 with surgery. Excellent local control was found post-surgery for class A
      and B tumours, and risk of cranial nerve damage was <1%. For class C1-4 tumours,
      local control was 80%-95% post-surgery (84% post-radiotherapy), and cranial nerve
      damage was found in 71%-76% (none post-radiotherapy; P < .05). There was no
      difference in treatment outcomes between tumours of different C class. For class
      C1-4De/Di tumours, local control was 38%-86% (98% post-radiotherapy; P < .05) and
      cranial nerve damage/complication rates were 67%-100% (3% post-radiotherapy; P <
      .05). C1-4DeDi tumours showed lesser local control and cranial nerve damage rates
      when compared to C1-4De tumours. CONCLUSIONS: An individual risk is constituted
      for surgery and radiotherapy, stratified per Fisch class. For class A and B
      tumours, surgery is a suitable treatment option. For class C and D tumours,
      radiotherapy results in lower complication rates and similar or better local
      control rates when compared to the surgical group.

PMID- 29222839
TI  - Decellularized human liver extracellular matrix (hDLM)-mediated hepatic
      differentiation of human induced pluripotent stem cells (hIPSCs).
AB  - Liver tissue engineering has emerged as a promising approach in organ
      transplantation but has been hampered by the lack of a reliable and readily
      available cell source. Human induced pluripotent stem cells hiPSCs have been
      highlighted as a desirable source, due to their differentiation potential,
      ability to self-renew, and the possibility of making patient-specific cells. We
      developed a decellularization protocol that efficiently removes cellular material
      while retaining extracellular matrix components. Subsequently, hiPSCs were
      differentiated on decellularized human liver extracellular matrix (hDLM)
      scaffolds using an established hepatic differentiation protocol. We demonstrate
      that using hDLM leads to upregulation markers of hepatic functions when compared
      with standard differentiation conditions. In addition, expression of a number of
      hepatic transcription and nuclear factors were found to be within levels
      comparable with those of primary human adult hepatocytes. Analysis of progression
      of differentiation on hDLM demonstrated that hepatic developmental marker
      expression was consistent with hepatic development. The hDLM-derived cells
      exhibited key hepatic characteristics that were comparable with those observed in
      primary neonatal human hepatocytes. We investigated the optimal timing of the
      introduction of hDLM into the differentiation protocol and found that the best
      results are obtained when cells are plated on hDLM since the earliest stages and
      accompanied by a progressive loss of sensitivity to substrate composition at
      later stages. The significance of this work is that it allows for the development
      of differentiation protocols that take into account signals from extracellular
      matrix, closely recapitulating of the in vivo micro-environment and resulting in
      cells that are phenotypically closer to mature hepatocytes.

PMID- 29222840
TI  - Detection of Neuropathic Pain in End-Stage Cancer Patients: Diagnostic Accuracy
      of Two Questionnaires.
AB  - INTRODUCTION: Neuropathic pain is a frequent consequence of cancer pain. Quite
      often, in the end stage, it is difficult to discern its presence and delineate
      its characteristics in the context of painful cancer complications. The aim of
      this study was to compare the diagnostic accuracy of the Douleur Neuropathique en
      4 Questions (DN4) and painDETECT questionnaires, which were translated to the
      patient's native language, for the diagnosis of peripheral neuropathic pain in
      oncology patients. METHODS: End-stage cancer patients who presented to the
      outpatient pain clinic were prospectively followed. At presentation, all patients
      completed the DN4 and painDETECT questionnaires, which had been translated to
      their native language, and the output was compared to the pain specialist's
      diagnosis of the neuropathic or non-neuropathic nature of the pain, which was
      considered as the gold standard. The diagnostic accuracy of both questionnaires
      was tested with receiver operating characteristic curves plotted from the data
      collected. RESULTS: Ninety patients (48.5% of 185 in total) presented with severe
      pain. Seventy-six had neuropathic pain (41.1%) and 109 had non-neuropathic pain.
      Of those with neuropathic pain, most had a mixed pain (bone or visceral in
      addition to neuropathic pain). The DN4 questionnaire had a sensitivity of 71.1%
      and a specificity of 88.7% in detecting neuropathic pain, with a cutoff value of
      >= 4, while the painDETECT questionnaire had a sensitivity of 26.3% and a
      specificity of 100%, with a cutoff value of >= 19. CONCLUSION: At standard cutoff
      values, the DN4 and painDETECT questionnaires, despite having been translated to
      the patient's native language, failed to adequately discriminate between
      neuropathic and non-neuropathic pain in our end-stage cancer patients.

PMID- 29222841
TI  - Evaluation of an ovary-on-a-chip in large mammalian models: Species specificity
      and influence of follicle isolation status.
AB  - The ability to grow oocytes from immature ovarian follicles in vitro has
      significant potential for fertility preservation; yet, it has proved challenging
      in large mammalian species due to the complex metabolic needs and long-term
      culture requirements. Currently, follicular incubations are based on a "static"
      system with manual exchange of medium. Despite the numerous advantages of
      conventional culturing approaches, recapitulating the native microenvironment and
      supporting the survival of ovarian follicles from large mammalian species still
      represent challenges. In this study, we utilized an innovative, dynamic
      microfluidic system to support the in vitro survival of domestic cat and dog
      follicles enclosed within the ovarian cortex or isolated from ovarian cortex.
      Results indicate both species-specific and tissue type-specific differences in
      response to microfluidic culture. Domestic cat but not dog ovarian cortical
      tissues maintained viability under flow similar to conventional agarose gel
      controls. Preantral stage isolated follicles from both species that grew most
      favourably in conventional alginate bead culture, but overall, there was no
      influence of culture system on expression of follicle development or oocyte
      health markers. This system represents an important exploration toward the
      development of an improved ovarian in vitro culture system of large mammalian
      species (e.g., cats and dogs), which has potential applications for fertility
      preservation, reproductive toxicology, and endangered mammal conservation
      efforts.

PMID- 29222842
TI  - Kinetic characterization of wild-type and mutant human thioredoxin glutathione
      reductase defines its reaction and regulatory mechanisms.
AB  - : In most cells, the thioredoxin (Trx) and glutathione systems are essential in
      maintaining redox homeostasis. The selenoprotein thioredoxin glutathione
      reductase (TGR) is a hybrid enzyme in which a glutaredoxin (Grx) domain is linked
      to a thioredoxin reductase (TrxR). Notably, the protein is also capable of
      reducing glutathione disulfide (GSSG), thus representing an important link
      between the two redox systems. In this study, we recombinantly produced human TGR
      (hTGR wild-type) by fusing its open reading frame with a bacterial selenocysteine
      insertion sequence element and co-expressing the construct in Escherichia coli
      together with the selA, selB, and selC genes. Additionally, the Sec->Cys mutant
      (hTGRU642C ) of the full-length protein, the isolated TrxR domain (hTGR151-643 )
      and the Grx domain containing a monothiol active site (hTGR1-150 ) were produced
      and purified. All four proteins were kinetically characterized in direct
      comparison using Trx, DTNB, HED, or GSSG as the oxidizing substrate.
      Interestingly, the HED reduction activity was Sec independent and comparable in
      the full-length protein and the isolated Grx domain, whereas the TrxR and
      glutathione reductase reactions were clearly selenocysteine dependent, with the
      GR reaction requiring the Grx domain. Site-directed mutagenesis studies revealed
      novel insights into the mechanism of GSSG reduction. Furthermore, we identified
      several glutathionylation sites in hTGR, including Cys93, Cys133, and Cys619, and
      an inhibitory effect of these modifications on enzyme activity. In contrast to
      other TGRs, for example, from platyhelminth parasites, hTGR did not exhibit
      hysteretic behavior. These findings provide new insights into the reaction
      mechanism and regulation of monothiol Grx-containing TGRs. DATABASE: EC numbers:
      1.8.1.9; 1.8.1.B1.

PMID- 29222844
TI  - Effect of age and body mass index on the yield of stromal vascular fraction.
AB  - OBJECTIVE: The aim of this study was to determine the influence of age, body mass
      index, and site of liposuction on the cell yield of SVF. METHODS: A prospective
      study was performed on 58 patients. The average age was 39 years old, with BMI <=
      25 or BMI >= 25. Fat tissue was harvested from the abdominal region, flanks, or
      thighs and SVF was isolated. RESULTS: The yield of viable SVF was evaluated by
      trypan blue, and the markers of stem cells were evaluated by flow cytometry. The
      cells were positive for stem cells markers, the age, sex of the patient had no
      impact on SVF cell yield with an average of 1.17 * 10^8. However, the BMI > 25
      had resulted in higher cell numbers, and the harvest site had a significant
      impact on cell yield with abdomen being the site of interest. CONCLUSION: These
      data demonstrate that the age of the person does not affect the cell yield of
      SVF; nevertheless, the donor site and BMI might be important factors in affecting
      cell number.

PMID- 29222843
TI  - Association of California Mastitis Test Scores with Intramammary Infection Status
      in Lactating Dairy Cows Admitted to a Veterinary Teaching Hospital.
AB  - BACKGROUND: Subclinical mastitis is of concern in veterinary hospitals because
      contagious mastitis pathogens might be unknowingly transmitted to susceptible
      cows and then back to their farm of origin. OBJECTIVES: To evaluate the
      California mastitis test (CMT) as an indicator of intramammary infection (IMI) in
      lactating dairy cows admitted to a veterinary hospital. ANIMALS: A total of 139
      admissions of 128 lactating dairy cows admitted to the University of Illinois
      Veterinary Teaching Hospital over a 2-year period. METHODS: A retrospective study
      with a convenience sample was conducted. Medical records of cows with CMT results
      and milk culture results for the day of admission were reviewed. Breed, age,
      season, maximum CMT score for the 4 quarters, maximum CMT score difference, and
      clinical diagnosis were evaluated as predictors of IMI by the chi-square test and
      stepwise logistic regression. RESULTS: An IMI was identified in 51% of quarters.
      For cows admitted without evidence of clinical mastitis, the sensitivity of a CMT
      score >=trace in predicting an IMI on a quarter or cow basis was 0.45 and 0.68,
      respectively. The distributions of maximal quarter CMT score and the maximum
      difference in quarter CMT score for cows without evidence of clinical mastitis
      did not differ (P = 0.28, P = 0.84, respectively) for cows with and without IMI.
      Stepwise logistic regression did not identify significant predictors of IMI in
      cows without clinical mastitis. CONCLUSIONS: Lactating dairy cattle admitted to a
      veterinary hospital should be managed as if they have an IMI, even in the absence
      of clinical mastitis.

PMID- 29222845
TI  - Severe drug-induced kidney injury in acute generalized exanthematous pustulosis.

PMID- 29222846
TI  - Influence of the three-dimensional culture of human bone marrow mesenchymal
      stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and
      Pannexin 3.
AB  - Because cell interactions play a fundamental role for cell differentiation, we
      investigated the expression of Pannexin 1 and Pannexin 3 in human bone marrow
      mesenchymal stromal cells (HBMSCs) in a three-dimensional (3D) microenvironment
      provided by a polysaccharide-based macroporous scaffold. The pannexin (Panx)
      family consists of three members, Panx1, Panx2, and Panx3. The roles of Panx
      large-pore ion and metabolite channels are recognized in many physiological and
      pathophysiological scenarios, but the role of these proteins in human
      physiological processes is still under investigation. Our study demonstrates that
      HBMSCs cultured within 3D scaffolds have induced Panx1 and Panx3 expression,
      compared with two-dimensional culture and that the Panx3 gene expression profile
      correlates with those of bone markers on mesenchymal stromal cells culture into
      the 3D scaffold. We showed that Panx1 is involved in the HBMSCs 3D cell-cell
      organization, as acting on the size of cellular aggregates, demonstrated by the
      use of Probenecid and the mimetic peptide 10panx1 as specific inhibitors.
      Inhibition of Panx3 using siRNA strategy shows to reduce the expression of
      osteocalcin as osteoblast-specific marker by HBMSCs cultured in 3D conditions,
      suggesting a role of this Panx in osteogenesis. Moreover, we evaluated Panx1 and
      Panx3 expression within the cellularized scaffolds upon subcutaneous implantation
      in NOG (NOD/Shi-scid/IL-2Rgammanull ) mice, where we could observe a more intense
      expression in the constructs than in the surrounding tissues in vivo. This study
      provides new insights on the expression of pannexins in HBMSCs on a 3D
      microenvironment during the osteogenic differentiation, in vitro and in vivo.

PMID- 29222847
TI  - Synthesis of novel norsufentanil analogs via a four-component Ugi reaction and in
      vivo, docking, and QSAR studies of their analgesic activity.
AB  - Novel substituted amino acid tethered norsufentanil derivatives were synthesized
      by the four-component Ugi reaction. Norsufentanil was reacted with succinic
      anhydride to produce the corresponding carboxylic acid. The resulting carboxylic
      acid has undergone a multicomponent reaction with different aldehydes, amines,
      and isocyanides to produce a library of the desired compounds. In all cases,
      amide bond rotation was observed in the NMR spectra. In vivo analgesic activity
      of the synthesized compounds was evaluated by a tail flick test. Very encouraging
      results were obtained for a number of the synthesized products. Some of the
      synthesized compounds such as 5a, 5b, 5h, 5j, and 5r were found to be more potent
      than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the
      compounds and mu and delta-opioid receptors were studied by molecular docking
      method. The relationship between the molecular structural features and the
      analgesic activity was investigated by a quantitative structure-activity
      relationship model. The results of the molecular modeling studies and the in vivo
      analgesic activity suggested that the majority of the synthesized compounds were
      more potent than sufentanil and norsufentanil.

PMID- 29222848
TI  - Digital image analysis agrees with visual estimates of adult bone marrow trephine
      biopsy cellularity.
AB  - INTRODUCTION: Evaluation of cellularity is an essential component of bone marrow
      trephine biopsy examination. The standard practice is to report the results as
      visual estimates (VE). Digital image analysis (DIA) offers the promise of more
      objective measurements of cellularity. METHODS: Adult bone marrow trephine biopsy
      sections were assessed for cellularity by VE. Sections were scanned using an
      Aperio AT2 Scanscope and analyzed using a Cytonuclear (version 1.4) algorithm on
      halo software. Intraclass correlation (ICC) was used to assess relatedness
      between VE and DIA, and between MRI and DIA for a separate subset of patients.
      Trephine biopsy sections from a subset of patients with bone marrow biopsies
      uninvolved by malignancy were assessed for age-related changes. RESULTS:
      Interobserver VE agreement was good to excellent. The ICC value was 0.81 for VE
      and DIA, and 0.50 for MRI and DIA. Linearity studies showed no statistically
      significant trend for age-related changes in cellularity in our cohort (r = -.29,
      P = .06). CONCLUSIONS: Agreement was good between VE and DIA. It may be possible
      to use DIA or VE to measure cellularity in the appropriate clinical scenario. The
      limited sample size precludes similar determinations for MRI calculations.
      Further studies examining healthy donors are necessary before making definitive
      conclusions regarding age and cellularity.

PMID- 29222849
TI  - Bone marrow transplantation improves motor activity in a mouse model of ataxia.
AB  - Ataxias are locomotor disorders that can have an origin both neural and muscular,
      although both impairments are related. Unfortunately, ataxia has no cure, and the
      current therapies are aimed at motor re-education or muscular reinforcement.
      Nevertheless, cell therapy is becoming a promising approach to deal with
      incurable neural diseases, including neuromuscular ataxias. Here, we have used a
      model of ataxia, the Purkinje Cell Degeneration (PCD) mutant mouse, to study the
      effect of healthy (wild-type) bone marrow transplantation on the restoration of
      defective mobility. Bone marrow transplants (from both mutant and healthy donors)
      were performed in wild-type and PCD mice. Then, a wide battery of behavioural
      tests was employed to determine possible motor amelioration in mutants. Finally,
      cerebellum, spinal cord, and muscle were analysed to study the integration of the
      transplant-derived cells and the origin of the behavioural changes. Our results
      demonstrated that the transplant of wild-type bone marrow restores the mobility
      of PCD mice, increasing their capabilities of movement (52-100% of recovery),
      exploration (20-71% of recovery), speed (35% of recovery), and motor coordination
      (25% of recovery). Surprisingly, our results showed that bone marrow transplant
      notably improves the skeletal muscle structure, which is severely damaged in the
      mutants, rather than ameliorating the central nervous system. Although a
      multimodal effect of the transplant is not discarded, muscular improvements
      appear to be the basis of this motor recovery. Furthermore, the results from our
      study indicate that bone marrow stem cell therapy can be a safe and effective
      alternative for dealing with movement disorders such as ataxias.

PMID- 29222850
TI  - Exploratory study of imagery rescripting without focusing on early traumatic
      memories for major depressive disorder.
AB  - BACKGROUND: Mental imagery has a more powerful impact on our emotions than
      thinking in words about the same material. Treating intrusive images with imagery
      rescripting (IR) has been reported for various disorders, including post
      traumatic stress disorder, social anxiety disorder, and bipolar disorder. There
      has been less research about IR as a major depressive disorder (MDD). AIMS: We
      examined whether IR without focusing on early traumatic memories is effective in
      MDD. METHODS: We enrolled 19 participants with MDD, who received 15 weekly
      sessions of full CBT, including two sessions for IR of intrusive images and,
      separately, for memory rescripting. Before and after the IR intervention,
      participants were asked to rate the intrusive images they experienced against, an
      intrusion index that included difficulty (interference with daily life),
      uncontrollability, distress caused by the negative image, and vividness. We
      recorded the contents of each participant's negative and positive imagery to
      classify these. RESULTS: The intrusion index scores decreased after the IR
      sessions. Negative images experienced by the participants while in a depressive
      mood were categorized into three different types: blame, social exclusion, and
      loneliness. The rescripted positive images were categorized into good relations
      and worthy self (competent self). CONCLUSIONS: These results suggest that IR of
      intrusive images without focusing on early traumatic memories may usefully be
      incorporated into routine CBT sessions for MDD.

PMID- 29222851
TI  - Convergent Validity of the Dutch Central Sensitization Inventory: Associations
      with Psychophysical Pain Measures, Quality of Life, Disability, and Pain
      Cognitions in Patients with Chronic Spinal Pain.
AB  - OBJECTIVE: Symptoms of central sensitization (CS) have been described in patients
      with chronic spinal pain (CSP). Although a gold standard to diagnose CS is
      lacking, psychophysical pain measures are often used. The Central Sensitization
      Inventory (CSI) is proposed as an alternative method and indirect tool for the
      evaluation of CS symptomatology. The aim of the current study was to evaluate the
      convergent validity of the CSI by investigating the association with
      psychophysical pain measures and self-reported measures of current pain
      intensity, quality of life, disability, and catastrophizing in CSP patients.
      METHODS: One hundred sixteen patients with nonspecific CSP were included in the
      present study. Patients completed the CSI, were subjected to pressure pain
      thresholds (PPTs) and a conditioned pain modulation (CPM) paradigm, and completed
      questionnaires for current pain intensity, quality of life, pain disability, and
      pain catastrophizing. RESULTS: Higher CSI scores were weakly correlated with
      lower PPTs (-0.276 <= r <= -0.237; all P <= 0.01) and not with CPM efficacy (r =
      0.017; P = 0.858). Higher CSI scores were moderately correlated with higher
      current pain intensity (r = 0.320; P < 0.001), strongly correlated with lower
      physical (r = -0.617; P < 0.001) and emotional (r = -0.635; P < 0.001) quality of
      life, and moderately correlated with higher pain disability (r = 0.472; P <
      0.001) and higher pain catastrophizing (r = 0.464; P < 0.001). CONCLUSION: The
      CSI was weakly associated with PPTs and not with CPM efficacy in CSP patients.
      Moderate to strong associations were found with current pain intensity, quality
      of life, disability, and catastrophizing. The current results illustrate that the
      CSI does not reflect a direct measure of CS, yet is a representation of general
      distress, possible originating from CS symptoms.

PMID- 29222852
TI  - Free-breathing whole-heart 3D cine magnetic resonance imaging with prospective
      respiratory motion compensation.
AB  - PURPOSE: To develop and validate a new prospective respiratory motion
      compensation algorithm for free-breathing whole-heart 3D cine steady-state free
      precession (SSFP) imaging. METHODS: In a 3D cine SSFP sequence, 4 excitations per
      cardiac cycle are re-purposed to prospectively track heart position.
      Specifically, their 1D image is reconstructed and routed into the scanner's
      standard diaphragmatic navigator processing system. If all 4 signals are in end
      expiration, cine image data from the entire cardiac cycle is accepted for image
      reconstruction. Prospective validation was carried out in patients (N = 17) by
      comparing in each a conventional breath-hold 2D cine ventricular short-axis stack
      and a free-breathing whole-heart 3D cine data set. RESULTS: All 3D cine SSFP
      acquisitions were successful and the mean scan time was 5.9 +/- 2.7 min. Left and
      right ventricular end-diastolic, end-systolic, and stroke volumes by 3D cine SSFP
      were all larger than those from 2D cine SSFP. This bias was < 6% except for right
      ventricular end-systolic volume that was 12%. The 3D cine images had a lower
      ventricular blood-to-myocardium contrast ratio, contrast-to-noise ratio, mass,
      and subjective quality score. CONCLUSION: The novel prospective respiratory
      motion compensation method for 3D cine SSFP imaging was robust and efficient and
      yielded slightly larger ventricular volumes and lower mass compared to breath
      hold 2D cine imaging. Magn Reson Med 80:181-189, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 29222853
TI  - Stemazole promotes survival and preserves stemness in human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are extremely delicate, and survive poorly
      under suboptimal culture conditions, severely restricting long-term studies and
      practical applications. Thus, a protective agent that promotes stem cell survival
      is urgently needed. In this study, we evaluated the protective effects of
      stemazole in single-cell and starved hESC cultures. Colony formation was
      quantified by alkaline phosphatase and immunofluorescence staining, while
      apoptosis was assessed by flow cytometry and TUNEL assay. Expression of hESC and
      other stem cell markers was evaluated by western blot, RT-PCR, and qPCR. We found
      that stemazole enhanced clonal expansion from single cells in dose-dependent
      fashion and clearly decreased apoptosis from 54.1% to 25.2%. Furthermore, the
      drug reduced apoptosis from 43.6% to 8.4% over 15 h of starvation, with 66% of
      stemazole-treated cells remaining viable after 2 weeks of starvation.
      Importantly, starved cells protected with stemazole retained the same
      proliferation and differentiation properties as cells in normal culture. In
      conclusion, stemazole significantly promotes survival of stem cells in single
      cell or starvation cultures without compromising stemness and pluripotency.

PMID- 29222854
TI  - Optical design of an in vivo laparoscopic lighting system.
AB  - This paper proposes an in vivo laparoscopic lighting system design to address the
      illumination issues, namely poor lighting uniformity and low optical efficiency,
      existing in the state-of-the-art in vivo laparoscopic cameras. The transformable
      design of the laparoscopic lighting system is capable of carrying purposefully
      designed freeform optical lenses for achieving lighting performance with high
      illuminance uniformity and high optical efficiency in a desired target region. To
      design freeform optical lenses for extended light sources such as LEDs with
      Lambertian light intensity distributions, we present an effective and complete
      freeform optical design method. The procedures include (1) ray map computation by
      numerically solving a standard Monge-Ampere equation; (2) initial freeform
      optical surface construction by using Snell's law and a lens volume restriction;
      (3) correction of surface normal vectors due to accumulated errors from the
      initially constructed surfaces; and (4) feedback modification of the solution to
      deal with degraded illuminance uniformity caused by the extended sizes of the
      LEDs. We employed an optical design software package to evaluate the performance
      of our laparoscopic lighting system design. The simulation results show that our
      design achieves greater than 95% illuminance uniformity and greater than 89%
      optical efficiency (considering Fresnel losses) for illuminating the target
      surgical region.

PMID- 29222856
TI  - Homocysteine as a non-classical risk factor for atherosclerosis in relation to
      pharmacotherapy of type 2 diabetes mellitus.
AB  - AIMS: The aim of our study was to evaluate which of the pharmacotherapeutic
      methods that are frequently used to treat type 2 diabetes is associated with the
      most beneficial profile in relation to pro-atherogenic homocysteine levels.
      PATIENTS AND METHODS: We measured the serum homocysteine level in 182 patients
      with type 2 diabetes treated with metformin (89), treated with insulin in
      combination with metformin (31), receiving sulfonylureas (31) and treated
      conventionally with insulin (31). The total homocysteine levels in the serum were
      assayed. To exclude the influence of selected metabolic and anthropometric
      factors on the differences between the examined groups, multivariate analysis of
      covariance was used (ANCOVA). In this analysis, serum homocysteine concentration
      was the dependent variable, while diabetes duration, waist circumference, HbA1c,
      1,5-anhydro-D-glucitol, fasting glycaemia and peptide C were used as covariates.
      RESULTS: The serum homocysteine levels in patients treated with insulin in
      monotherapy were significantly higher than what was observed in the metformin
      treated subjects and in the patients receiving insulin combined with metformin.
      The analysis of covariance also confirmed that the differences between the
      therapeutic groups were affected by waist circumference and the C-peptide levels.
      CONCLUSION: We conclude that conventional insulin therapy may have a negative
      effect on pro-atherogenic homocysteine levels in patients with type 2 diabetes.
      This study revealed that pro-atherogenic homocysteine levels may not only be
      modified by pharmacotherapy of type 2 diabetes, but also by beta cell secretory
      function and abdominal obesity.

PMID- 29222855
TI  - Non-Euclidean phasor analysis for quantification of oxidative stress in ex vivo
      human skin exposed to sun filters using fluorescence lifetime imaging microscopy.
AB  - Chemical sun filters are commonly used as active ingredients in sunscreens due to
      their efficient absorption of ultraviolet (UV) radiation. Yet, it is known that
      these compounds can photochemically react with UV light and generate reactive
      oxygen species and oxidative stress in vitro, though this has yet to be validated
      in vivo. One label-free approach to probe oxidative stress is to measure and
      compare the relative endogenous fluorescence generated by cellular coenzymes
      nicotinamide adenine dinucleotides and flavin adenine dinucleotides. However,
      chemical sun filters are fluorescent, with emissive properties that contaminate
      endogenous fluorescent signals. To accurately distinguish the source of
      fluorescence in ex vivo skin samples treated with chemical sun filters,
      fluorescence lifetime imaging microscopy data were processed on a pixel-by-pixel
      basis using a non-Euclidean separation algorithm based on Mahalanobis distance
      and validated on simulated data. Applying this method, ex vivo samples exhibited
      a small oxidative shift when exposed to sun filters alone, though this shift was
      much smaller than that imparted by UV irradiation. Given the need for
      investigative tools to further study the clinical impact of chemical sun filters
      in patients, the reported methodology may be applied to visualize chemical sun
      filters and measure oxidative stress in patients' skin.

PMID- 29222857
TI  - Serum levels of the S100B protein and neuron-specific enolase are associated with
      mortality in critically ill patients.
AB  - INTRODUCTION: Evaluation of the prognostic potential of the S100B protein and
      neuron-specific enolase (NSE) as predictors of mortality in critically ill
      patients in intensive care units (ICU). MATERIALS AND METHODS: The study was
      conducted on 62 patients. Basic clinical variables and blood samples for S100B
      and NSE level testing were obtained during the first four days after admission.
      Mortality was described as the patient's death during hospitalization in the ICU.
      RESULTS: 35% of the patients had died. The level of S100B and NSE was
      significantly higher in non-survivors in comparison with survivors (p=0.007 and
      p=0.02, respectively). Mortality risk was significantly higher in patients with
      higher levels of biomarkers than the reference values for S100B (OR 9.00; 95% CI
      2.38-33.99; p<0.001) as well as for NSE (OR 5.75; 95%CI 1.31-25.27; p=0.016).
      Receiver operating characteristic proved that S100B is a better mortality
      predictor than NSE (AUC 0.76 for S100B and 0.68 for NSE). From all the other
      variables, the Apache II score turned out to be the only significant predictor of
      mortality (AUC 0.88). CONCLUSION: There is a significant correlation between
      mortality in the ICU and increased serum concentration of S100B and NSE. This
      correlation is stronger for S100B. Testing for serum levels of S100B and NSE may
      be useful for prediction of treatment outcomes in the ICU patients.

PMID- 29222859
TI  - Physicochemical properties and cytotoxicity of hydrogels based on Beetosan(r)
      containing sage and bee pollen.
AB  - Currently, increasing attention is being paid to issues related to environmental
      protection, waste management, as well as to the development of polymers with
      useful properties. The research presented here involved preparation of hydrogels
      based on Beetosan(r) - a chitosan derived from the multi-stage processing of dead
      bees. Moreover, hydrogels were additionally modified with natural substances -
      i.e. bee pollen and extract of Salvia officinalis (sage) that are well known for
      the presence of many compounds with beneficial properties from a medical point of
      view. Materials have been first obtained by photopolymerization. Then, their
      surface morphology, wettability and cytotoxicity to selected cell lines have been
      determined. It can be stated that such combination of Beetosan(r) hydrogel matrix
      and the mentioned additives resulted in a preparation of polymers characterized
      by negative impact on cancer cells. Impact of hydrogels with sage is slightly
      more intense due to the presence of substances such as ursalic or rosmaric acid
      that are characterized to have anticancer activity. Such negative impact has not
      been observed in case of studies using fibroblasts. Furthermore, addition of
      natural substances into hydrogels resulted in a more homogeneous surface and in
      the decrease of wettability angle of the tested polymers. It can be concluded
      that the use of natural-derived reagents and synthesis of polymers using these
      reagents (as a result of environmentally friendly photopolymerization) yields
      materials with interesting properties for medical purposes, with particular
      emphasis on antitumor activity, and without significant negative impact on
      fibroblasts.

PMID- 29222858
TI  - Obesity, lipid profiles and oxidative stress in children after liver
      transplantation.
AB  - PURPOSE: In adult liver transplant recipients, coronary artery disease and
      congestive heart failure are significant cause of morbidity and mortality. This
      may be attributed to the long-term immunosuppressive treatment, mostly with
      calcineurin inhibitors and steroids, which in long-term may be associated with
      hyperlipidemia, oxidative stress and cardiovascular complications. Since such
      data for children is sparse, the aim of this study was to assess the lipid and
      oxidative stress markers after pediatric liver transplantation (LTx). METHOD: We
      performed prospective analysis of 74 children, at the median age of 7.9 (2.8
      11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores,
      cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI,
      ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress
      and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx),
      asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein
      (oxyLDL). At baseline, the results were compared with a healthy age-and-sex
      matched control group. After 3.1+/-0.3 year follow-up we repeated all
      investigations and compared them with the baseline results. RESULTS: At the
      baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the
      median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI
      >85th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen
      patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal
      levels in all patients. Compared to the controls, there were no significant
      differences in lipid profiles but we found decreased GSH (p<0.001) and GPx
      (p<0.001) which play role as an antioxidant defense. OS markers were higher in
      the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by
      HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained
      within normal ranges in all patients. After 3.1-year follow-up, the BMI >95th and
      >85Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL
      decreased, whilst GSH and GPx increased when compared to the baseline. There was
      also significant decrease in apoB and Lp(a). CONCLUSION: Children after LTx had
      normal lipid profiles when compared to controls, however there is a tendency for
      hypercholesterolemia and obesity, which may play a role in cardiovascular
      complications in the future. Some markers of oxidative stress were increased
      after LTx, however further investigations are required to establish its clinical
      significance.

PMID- 29222860
TI  - Adenosine-sensitive Wolff-Parkinson-White: Longer time across the
      atrioventricular groove.
AB  - BACKGROUND: Successful ablation sites in Wolff-Parkinson-White syndrome (WPW) are
      characterized by short atrioventricular (AV) intervals. Approximately 15% of
      patients with WPW have adenosine-sensitive accessory pathways (APs). We sought to
      determine if local AV intervals of adenosine-sensitive APs are different from
      those of adenosine-insensitive APs in patients with WPW. METHODS: Patients <=21
      years with WPW and adenosine-sensitive APs who underwent successful ablation over
      a 9-year period were included. Patients with WPW and adenosine-insensitive APs
      were matched by age and weight in a 1:2 case-control design. AP location,
      antegrade and retrograde conduction properties, supraventricular tachycardia
      (SVT) inducibility, local AV interval, interval from delta wave onset to local
      ventricular activation (del-V), and time to loss of preexcitation were reviewed.
      RESULTS: Fourteen patients with adenosine-sensitive APs and 28 with adenosine
      insensitive APs were included. Patients with adenosine-sensitive APs had minimum
      1:1 antegrade AP conduction at a longer median paced cycle length (380,
      interquartile range [IQR] 295 to 585 ms vs 290, IQR 250 to 330 ms, P = 0.046),
      were less likely to have inducible SVT (35.7% vs 75.0%, P = 0.035), and had a
      longer median local AV interval (40.5, IQR 30.8 to 58.3 ms vs 32.0, IQR 29.3 to
      37.8 ms, P = 0.029) when compared to those with adenosine-insensitive APs.
      CONCLUSION: Patients with WPW and adenosine-sensitive APs have 1:1 antegrade AP
      conduction at longer cycle lengths, lower likelihood of SVT induction, and longer
      local AV intervals when compared to those with adenosine-insensitive APs. In
      patients with WPW, it may be important to consider adenosine response when
      selecting appropriate ablation targets.

PMID- 29222861
TI  - Zero-fluoroscopy permanent pacemaker implantation using Ensite NavX system:
      Clinical viability or fanciful technique?
AB  - BACKGROUND: Fluoroscopy is the imaging modality routinely used for cardiac device
      implantation and electrophysiological procedures. Due to the rising concern
      regarding the harmful effects of radiation exposure to both the patients and
      operation staffs, novel 3D mapping systems have been developed and implemented in
      electrophysiological procedure for the navigation of catheters inside the heart
      chambers. Their applicability in cardiac device implantation has been rarely
      reported. Our aim is to evaluate the feasibility and safety of permanent
      pacemaker implantation without fluoroscopy. METHODS AND RESULTS: From January
      2012 to June 2016, six patients (50 +/- 15 years, four of six were female, one of
      who was at the 25th week of gestation) who underwent permanent pacemaker
      implantation were included (zero-fluoroscopy group). Data from 20 consecutive
      cases of implantation performed under fluoroscopy guidance were chosen as a
      control group (fluoroscopy group). Total implantation procedure time for single
      chamber pacemaker was 51.3 +/- 13.1 minutes in the zero-fluoroscopy group and
      42.6 +/- 7.4 minutes in the fluoroscopy group (P  =  0.155). The implantation
      procedural time for a dual-chamber pacemaker was 88.3 +/- 19.6 minutes and 67.3
      +/- 7.6 minutes in the zero-fluoroscopy and fluoroscopy groups (P  =  0.013),
      respectively. No complications were observed during the procedure and the follow
      up in the two groups, and all pacemakers worked with satisfactory parameters.
      CONCLUSION: Ensite NavX system can be used as a reliable and safe zero
      fluoroscopy approach for the implantation of single- or dual-chamber permanent
      pacemakers in specific patients, such as pregnant women or in extreme situations
      when the x-ray machine is not available.

PMID- 29222862
TI  - Photocytotoxic Copper(II) Complexes with Schiff-Base Scaffolds for Photodynamic
      Therapy.
AB  - Photodynamic therapy (PDT) is a promising and minimally invasive method for the
      treatment of superficial diseases, and photosensitizers with high phototoxicity
      indices (defined as (IC50dark )/(IC50irradiation )) are essential for the
      development of ideal photosensitizing properties for this technology. Herein, we
      report a series of photocytotoxic copper(II) complexes [Cu(R QYMP)(dppn)] (R
      QYMP=N,N,O-tridentate Schiff-base derivatives, dppn=benzo[i]dipyrido[3,2-a;2',3'
      c]phenazine), the structures of which have been confirmed by mass spectrometry
      and FTIR spectroscopy. X-ray crystallography revealed that the CuN4 O core of the
      [Cu(cumyl QYMP)(dppn)](ClO4 ) complex (3) has a distorted square-pyramidal
      geometry. Phototoxicity indices of 329 against human squamous cell carcinoma
      (SCC15) and 296 against basal cell carcinoma (BCC) cell lines have been
      determined with [Cu(3-OMe QYMP)(dppn)](ClO4 ) (4). This can be attributed to the
      formation of reactive oxygen species, cell apoptosis, and caspase-3 activation,
      indicating high potential of complex 4 as a photosensitizer candidate in PDT.
      Thus, copper complexes bearing suitable Schiff-base ligands with a dppn co-ligand
      may be considered for the design of efficient metal-based anticancer agents for
      PDT.

PMID- 29222863
TI  - Immobilization of carbonic anhydrase on polyvinylidene fluoride membranes.
AB  - In recent years, the application of carbonic anhydrase (CA) in CO2 removal has
      attracted great interest. However, obtaining high enzyme recovery activity is
      difficult in existing immobilization techniques. In this work, water plasma
      treated poly(vinylidene fluoride) (PVDF) membranes were modified via 3
      aminopropyl triethoxy silane (KH550) or gamma-(2, 3-epoxypropoxy) propyl
      trimethoxy silane (KH560), and then CA was attached. The immobilization process
      was optimized, and the catalytic properties of PVDF-attached CA were
      characterized. The maximum activity recovery of PVDF-KH550-CA was 60%, whereas
      that of PVDF-KH560-CA was 33%. The Km values of PVDF-KH550-CA, PVDF-KH560-CA, and
      free enzyme were 9.97 +/- 0.37, 12.5 +/- 0.2, and 6.18 +/- 0.23 mM, respectively,
      and their Kcat /Km values were 206 +/- 2, 117 +/- 5, and 488 +/- 4 M-1 .Sec-1 .
      PVDF-attached CA shows excellent storage stability and reusability, and their
      half-life values were 82 and 78 days at 4  degrees C. At 25  degrees C, they were
      50 and 37 days, respectively. PVDF-KH550-CA and PVDF-KH560-CA retained
      approximately 85% and 72% of the initial activity after undergoing 10 cycles. In
      the presence of them, the generation rates of CaCO3 were 76% and 65% of the free
      CA system, which were 1.6 and 1.3 times that of the blank system, respectively.
      Its role in accelerating CO2 sequestration holds great promise for its practical
      application.

PMID- 29222864
TI  - Effects of cardiac resynchronization therapy after inferior myocardial infarction
      on secondary mitral regurgitation and mitral valve geometry.
AB  - BACKGROUND: The effects of cardiac resynchronization therapy (CRT) on secondary
      mitral regurgitation (MR), and mitral valve (MV) and left ventricular (LV)
      geometry, in patients with prior inferior myocardial infarction is not clearly
      defined. We assessed these outcomes utilizing two-dimensional echocardiography,
      and analyzed echocardiographic geometric variables that may correlate with follow
      up MR severity. METHODS: Between 2009 and 2012, 229 CRT were implanted. Twenty
      two had prior inferior myocardial infarction, >=mild MR at baseline, and serial
      echocardiography. A left bundle branch block was present in 12 (54.5%) patients.
      The pre-CRT and follow-up echocardiograms were analyzed for: (1) MR severity; (2)
      MV and LV geometry; and (3) LV remodeling. RESULTS: The median follow-up time was
      2.2 years (interquartile range, 0.7-4). In 16 patients without an inferior
      myocardial scar, there was a reduction in MR jet area/left atrial area ratio
      (33.2% vs 25.8%; P = 0.06) and MR grade (2.3 vs 1.8; P = 0.05), and an increased
      LV ejection fraction (26.1% vs 30.9%; P = 0.04) and end-systolic posterior
      ventricular sulcus-anterolateral papillary muscle angle (133.9 vs 143.9 degrees;
      P = 0.01). In six patients with scar, there was no change in LV or MR parameters.
      Regression analysis revealed linear associations between baseline MV tenting
      height (r = 0.57; P = 0.006), LV end-diastolic diameter index (r = 0.5; P =
      0.02), mitral septolateral annular diameter (r = 0.48; P = 0.03), and MV tenting
      area (r = 0.46; P = 0.03), with follow-up MR jet area/left atrial area ratio.
      CONCLUSIONS: In patients with prior inferior myocardial infarction and no scar,
      CRT is associated with decreased MR severity, and improved papillary muscle
      alignment and LV systolic function at follow-up.

PMID- 29222865
TI  - Multipoint pacing improves peripheral hemodynamic response: Noninvasive
      assessment using radial artery tonometry.
AB  - BACKGROUND: Multipoint left ventricular (LV) pacing (MultiPointTM Pacing [MPP],
      Abbott, Sylmar, CA, USA) improves the response rate to cardiac resynchronization
      therapy (CRT). We evaluated the feasibility of noninvasive radial artery
      tonometry (RAT) to characterize arterial pressure morphology changes (pre
      ejection period [PEP] and ejection duration [ED]) between conventional CRT and
      MPP pacing interventions. METHODS: Patients with a MPP-enabled CRT device (Quadra
      Assura MPTM, Abbott) underwent noninvasive RAT assessment (SphygmoCor CVMS, AtCor
      Medical Inc., Itasca, IL, USA) at 3-6 months after implantation. A pacing
      protocol was performed in a randomized order including one optimized conventional
      biventricular CRT (CONV) configuration using the distal electrode and five MPP
      configurations. The PEP, ED, and PEP/ED ratio were determined for each
      intervention from the RAT pressure waveform and electrocardiogram. RESULTS:
      Pressure waveforms were successfully recorded in 19 patients (89% male, QRS 147
      +/- 16 ms, 63% ischemic). In 17/19 (89%) patients, at least one MPP intervention
      resulted in improved PEP, ED, and PEP/ED compared to CONV. The MPP intervention
      with greatest separation of LV cathodes and minimum intra-LV delay significantly
      improved PEP (mean PEP -15 +/- 33% vs -8 +/- 32% [CONV], P = 0.04) and ED (mean
      ED +8 +/- 8% [MPP] vs +4 +/- 7% [CONV], P = 0.02), and PEP/ED (-0.07 +/- 0.14
      [MPP] vs -0.04 +/- 0.13 [CONV], P = 0.02) compared with CONV. CONCLUSIONS:
      Noninvasive RAT efficiently characterizes changes in PEP and ED between CONV and
      MPP interventions. MPP configurations using the widest separation among LV
      cathodes and minimum intra-LV delay may significantly improve RAT-derived
      parameters as compared to conventional CRT.

PMID- 29222866
TI  - Outcome of antibody-mediated rejection compared to acute cellular rejection after
      pediatric heart transplantation.
AB  - Outcomes of ACR after pediatric HTx have been well described, but less has been
      reported on outcomes of AMR. We compared the clinical characteristics and
      cardiovascular outcomes (composite end-point of death, retransplantation, or
      allograft vasculopathy) of pediatric HTx recipients with AMR, ACR, and no
      rejection in a retrospective single-center study of 104 recipients. Twenty were
      treated for AMR; 15 were treated for ACR. Recipients with AMR had an increased
      frequency of congenital heart disease (90% vs ACR 67% vs no rejection 59%, P =
      .03), homograft (68% vs 7% vs 18%, P < .001), HLA sensitization (45% vs 13% vs
      13%, P = .008), and positive cross-match (30% vs 7% vs 9%, P = .046). AMR caused
      hemodynamic compromise more often than ACR (39% vs 4%, P = .02). AMR recipients
      had worse cardiovascular outcome than recipients with ACR or no rejection (40% vs
      20% vs 8.6%, P = .003). In bivariate Cox analysis, AMR (HR 4.1, CI 1.4-12.0, P =
      .009) and ischemic time (HR 1.6, CI 1.1-2.3, P = .02) were associated with worse
      cardiovascular outcome; ACR was not. In summary, pediatric HTx recipients who
      develop AMR have worse cardiovascular outcome than recipients who develop only
      ACR or experience no rejection at all.

PMID- 29222867
TI  - Asymmetric Total Syntheses and Structure Confirmation of Chlorofucins and
      Bromofucins.
AB  - Substrate-controlled asymmetric total syntheses and structure confirmation of (+)
      (3E)- and (-)-(3Z)-chlorofucin [(E)-1 a and (Z)-1 a], and (+)-(3E)- and (-)-(3Z)
      bromofucin [(E)-1 b and (Z)-1 b] were accomplished. Our syntheses feature as key
      steps haloetherification (either 'conventional' or 'one-pot organoselenium
      mediated') of alpha,alpha'-trans-gamma,delta-unsaturated oxocene alcohol 9 and
      our (E)- and (Z)-selective cross-metathesis (CM) protocols. More importantly, a
      rationale is provided for the strikingly different pathways followed by
      alpha,alpha'-trans-gamma,delta-unsaturated oxocene alcohol 9 and its alpha,alpha'
      cis isomer 9' in the presence of different electrophiles during the
      intramolecular electrophilic addition reactions.

PMID- 29222868
TI  - Synthesis of New Microporous Zincosilicates with CHA Zeolite Topology as
      Efficient Platforms for Ion-Exchange of Divalent Cations.
AB  - There is growing interest to develop zeolite materials capable of stabilizing
      divalent cations such as Cu2+ , Fe2+ , and Ni2+ for catalytic applications.
      Herein the synthesis of a new microporous zincosilicate with CHA zeolite topology
      is reported for the first time, by particularly focusing on the mixing procedures
      of the raw materials to prevent the precipitation of zinc oxides/hydroxides and
      the formation of impurity phases. The obtained zincosilicate CHA products possess
      remarkably higher ion-exchange ability for catalytically useful, divalent
      cations, demonstrated here using Ni2+ as an example, compared to that of
      aluminosilicate and zincoaluminosilicate analogs. It is anticipated that these
      zincosilicate CHA materials can be an efficient platform for several important
      catalytic reactions. In addition, the present finding would provide a general
      guideline for effective substitution of other heteroatoms into the zeolite
      frameworks.

PMID- 29222869
TI  - New generation cardioverter-defibrillator lead with a floating atrial sensing
      dipole: Long-term performance.
AB  - OBJECTIVES: The study aim is to present the long-term performance of a new
      generation implantable cardioverter defibrillator (ICD) electrode with floating
      atrial dipole (Linox S DX, Biotronik, Berlin, Germany). BACKGROUND: The single
      ICD electrode with a floating dipole in the atrial chamber was introduced about
      15 years ago to overcome risk of inappropriate shock. METHODS: After
      implantation, internal electrocardiogram data were prospectively collected via
      telemonitoring (Home Monitoring, Biotronik). RESULTS: A total of 93 patients
      (81.5% male, 18.5% female; 58.9 +/- 12.3 years) were implanted with a single
      chamber ICD using the Linox S DX. Patients were followed up for a median of 693
      days (33-2,460 days). At time of implantation average p-wave value was 3.5 +/-
      1.7 mV and remained stable throughout follow-up with an average value of 3.7 +/-
      1 mV (P = 0.2). A total of 460 arrhythmic episodes were recorded and 185 (40.2%)
      were incorrectly stratified by the device software. Seven patients (7.5%)
      experienced inappropriate ICD therapy. In three patients, VT episodes were not
      detected and remained untreated. CONCLUSIONS: Although the Linox S DX lead
      presents a satisfactory long-term stability of the atrial sensing, many of the
      messages sent to the device during follow-up were incorrectly classified by the
      ICD software. As a result, inappropriate therapy occurred with a rate similar to
      that observed with dual-chamber ICDs, but some malignant arrhythmias remained
      undiagnosed and untreated while occurring. Results in larger prospective cohorts
      should be analyzed and software improvements of the device should be suggested to
      overcome these potential drawbacks.

PMID- 29222870
TI  - A Route to Base Coordinate Silicon Difluoride and the Silicon Trifluoride
      Radical.
AB  - Silicon difluoride (SiF2 ) is highly unstable at room temperature and condenses
      at this temperature rapidly to a polymeric material of unknown structure.
      Therefore, the isolation of a stable monomeric silicon difluoride species is a
      challenging task. The cyclic alkyl(amino) carbene (cAAC) coordinated silicon
      difluoride was isolated as (cAAC)2 SiF2 (2), synthesized from the reduction of
      cAAC-SiF4 (1) by using two equivalents of KC8 in the presence of one equivalent
      of cAAC. In the solid state, compound 2 is stable at room temperature for a long
      time under inert conditions. The reduction of compound 1 in the presence of one
      equivalent KC8 resulted in the first stable silicon trifluoride monoradical
      (cAAC)SiF3 (3).

PMID- 29222871
TI  - Myelin extracellular leaflet compaction requires apolipoprotein D membrane
      management to optimize lysosomal-dependent recycling and glycocalyx removal.
AB  - To compact the extracellular sides of myelin, an important transition must take
      place: from membrane sliding, while building the wraps, to membrane adhesion and
      water exclusion. Removal of the negatively charged glycocalyx becomes the
      limiting factor in such transition. What is required to initiate this membrane
      zipping process? Knocking-out the Lipocalin Apolipoprotein D (ApoD), essential
      for lysosomal functional integrity in glial cells, results in a specific defect
      in myelin extracellular leaflet compaction in peripheral and central nervous
      system, which results in reduced conduction velocity and suboptimal behavioral
      outputs: motor learning is compromised. Myelination initiation, growth,
      intracellular leaflet compaction, myelin thickness or internodal length remain
      unaltered. Lack of ApoD specifically modifies Plp and P0 protein expression, but
      not Mbp or Mag. Late in myelin maturation period, ApoD affects lipogenic and
      growth-related, but not stress-responsive, signaling pathways. Without ApoD, the
      sialylated glycocalyx is maintained and ganglioside content remains high. In
      peripheral nervous system, Neu3 membrane sialidase and lysosomal Neu1 are
      coordinately expressed with ApoD in subsets of Schwann cells. ApoD-KO myelin
      becomes depleted of Neu3 and enriched in Fyn, a kinase with pivotal roles in
      transducing axon-derived signals into myelin properties. In the absence of ApoD,
      partial permeabilization of lysosomes alters Neu1 location as well. Exogenous
      ApoD rescues ApoD-KO hypersialylated glycocalyx in astrocytes, demonstrating that
      ApoD is necessary and sufficient to control glycocalyx composition in glial
      cells. By ensuring lysosomal functional integrity and adequate subcellular
      location of effector and regulatory proteins, ApoD guarantees the glycolipid
      recycling and glycocalyx removal required to complete myelin compaction.

PMID- 29222872
TI  - Comparison of therapeutic effects of EGFR-tyrosine kinase inhibitors on 19Del and
      L858R mutations in advanced lung adenocarcinoma and effect on cellular immune
      function.
AB  - BACKGROUND: We compared the therapeutic effect of EGFR-tyrosine kinase inhibitors
      (TKIs) on 19Del and L858R mutations in advanced lung adenocarcinoma on cellular
      immune function and explored the factors influencing the curative effect and
      prognosis. METHODS: Clinical efficacy in the selected 71 patients with lung
      adenocarcinoma, including 52 patients with 19Del and L858R mutations and 19 wild
      type patients treated with EGFR-TKIs was retrospectively analyzed. The response
      rate (RR), disease control rate (DCR), progression-free survival (PFS), overall
      survival (OS), and cellular immune function were analyzed. RESULTS: The RR, DCR,
      PFS, and OS of the 19Del group were higher than those of the L858R group;
      however, there were no statistically significant differences between the groups.
      chi2 test results revealed that gender, smoking, and EGFR mutations were
      associated with DCR. Log-rank analytical results showed that EGFR mutation type
      was correlated to PFS and OS. Multivariate analysis implied that disease control
      and mutation type of EGFR were independent prognostic factors of OS. Following
      TKI treatment, the number of CD3+, CD4+, and NK cells and the CD4+/CD8+ratio
      increased in both mutation groups; however the results were not statistically
      significant. There was also no significant difference in the upregulation of
      immunological function observed, with 46.43% in the 19Del mutation and 45.83% in
      the L858R mutation group. CONCLUSION: EGFR 19Del and L858R mutations are good
      biomarkers for predicting the clinical response of EGFR-TKIs. 19Del mutations may
      have a better clinical outcome.

PMID- 29222873
TI  - Calcineurin inhibitor-associated electrolyte disturbances after pediatric renal
      transplantation: Could fludrocortisone therapy have a role?

PMID- 29222874
TI  - A homochiral porous organic cage with large cavity and pore windows for the
      efficient gas chromatography separation of enantiomers and positional isomers.
AB  - Porous organic cages composed of discrete cage molecules have attracted
      considerable recent attention as gas adsorption materials and separation media.
      In this study, we report a homochiral porous organic cage CC5 with a large cavity
      and pore windows as a novel stationary phase for high-resolution gas
      chromatographic separations. The capillary column was prepared by a static
      coating method. A large number of racemic compounds have been resolved on the
      coated capillary column, including derivatized amino acids, alcohols, alcohol
      amines, esters, ethers, ketones, and epoxides. It is interesting that the CC5
      coated capillary column exhibits significant chiral recognition complementarity
      to a commercial beta-DEX 120 column and a previously reported homochiral porous
      organic cage CC3-R-coated column, which could expand the range of the analytes
      amenable to separation on porous organic cage-based capillary columns. Moreover,
      the fabricated column also shows excellent selectivity for the separation of
      positional isomers, including the challenging ethylbenzene and xylene isomers.
      Experimental results demonstrate an excellent separation performance and
      stability of the CC5-coated column, making it promising for gas chromatography
      applications.

PMID- 29222875
TI  - The incidence and outcomes of delayed response to cardiac resynchronization
      therapy.
AB  - BACKGROUND: The incidence and clinical outcomes of delayed response to cardiac
      resynchronization therapy (CRT) have not been well clarified. We aimed to observe
      the incidence and prognosis of delayed response and to identify its possible
      mechanisms. METHODS: A total of 115 CRT patients were retrospectively analyzed in
      our study. Patients who met the enrollment criteria were divided into two groups:
      group A, conventional responders who showed response at 1-year follow-up, and
      group B, delayed responders who showed response after 1-year follow-up. CRT
      response was defined as an absolute increase of >=10% in left ventricular
      ejection fraction. RESULTS: Fifty-two patients (61 +/- 12 years, 37 male)
      experienced conventional response to CRT and 17 patients (63 +/- 11 years, 10
      male) experienced delayed response. The mean follow-up time was 5.2 +/- 2.4
      years. The incidence of delayed response was 14.8% (17/115). All-cause mortality
      and hospitalization rates for heart failure were similar for delayed and
      conventional responders. Multivariate logistic regression analysis revealed that
      scar burden > 35% was an independent predictor of CRT delayed response (odds
      ratio 8.794, P  =  0.038). CONCLUSIONS: A significant proportion of patients
      demonstrated delayed response to CRT. The delayed responders had a good prognosis
      that was similar to that of conventional responders. More scar burden might be
      related to the incidence of delayed response.

PMID- 29222876
TI  - Asia Pacific Clinical Nutrition Society Award for 2018: Professor Chunming Chen.

PMID- 29222877
TI  - Critical examination of evidence for the nutritional status of children in Papua
      New Guinea - a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Undernutrition remains a significant cause of
      childhood illness, poor growth, development, and death in Papua New Guinea (PNG).
      Studies on child nutritional outcomes in PNG vary by design, measurement
      protocols and quality. We conducted a systematic review to assess the evidence
      for the prevalence of child undernutrition across different study populations,
      geographical locations and time periods. METHODS AND STUDY DESIGN: Six electronic
      databases and additional grey literature were searched for articles describing
      the nutritional status by wasting, stunting and underweight, of PNG children
      under five years of age, published between 1990 and April 2015. Prevalence data
      using different scales of measurement and reference populations were standardized
      according to WHO protocols. RESULTS: The search yielded 566 articles, of which,
      31 studies met the inclusion criteria. The prevalence of child undernutrition
      varied from 1% to 76% for wasting (median 11%), 5% to 92% for stunting (median
      51%), and 14% to 59% for underweight (median 32%). Wide variations exist
      according to the index used for measurement, the population characteristics and
      the geographical region in which they live. Prevalence estimates increase
      significantly when data using different scales of measurement and population
      references are standardized to the WHO protocols. CONCLUSIONS: Child
      undernutrition in PNG is regionally variable due to a complex interplay of
      poverty, disease, food-security, cultural, environmental and sociopolitical
      issues requiring a complex mix of solutions by governments, health systems and
      local communities. Area- specific surveys using multiple measures are necessary
      to inform local solutions for this important problem.

PMID- 29222878
TI  - Non-communicable diseases, food and nutrition in Vietnam from 1975 to 2015: the
      burden and national response.
AB  - BACKGROUND AND OBJECTIVES: This review manuscript examines the burden and
      national response to non-communicable diseases (NCDs), food and nutrition
      security in Vietnam from 1975 to 2015. METHODS AND STUDY DESIGN: We extracted
      data from peer-reviewed manuscripts and reports of nationally representative
      surveys and related policies in Vietnam. RESULTS: In 2010, NCDs accounted for
      318,000 deaths (72% of total deaths), 6.7 million years of life lost, and 14
      million disability-adjusted life years in Vietnam. Cardiovascular diseases,
      cancers, chronic obstructive pulmonary disease, and diabetes mellitus were major
      contributors to the NCD burden. Adults had an increased prevalence of overweight
      and obesity (2.3% in 1993 to 15% in 2015) and hypertension (15% in 2002 to 20% in
      2015). Among 25-64 years old in 2015, the prevalence of diabetes mellitus was
      4.1% and the elevated blood cholesterol was 32%. Vietnamese had a low physical
      activity level, a high consumption of salt, instant noodles and sweetened non
      alcoholic beverages as well as low consumption of fruit and vegetables and
      seafood. The alcohol consumption and smoking prevalence were high in men.
      Exposure to second-hand tobacco smoke was high in men, women and youths at home,
      work, and public places. In Vietnam, policies for NCD prevention and control need
      to be combined with strengthened law enforcement and increased program coverage.
      There were increased food production and improved dietary intake (e.g., energy
      intake and protein-rich foods thanked to appropriate economic, agriculture, and
      nutrition strategies. CONCLUSIONS: NCDs and their risk factors are emerging
      problems in Vietnam, which need both disease-specific and sensitive strategies in
      health and related sectors.

PMID- 29222879
TI  - Prevalence, cause and diagnosis of lactose intolerance in children aged 1-5
      years: a systematic review of 1995-2015 literature.
AB  - BACKGROUND AND OBJECTIVES: To assess the prevalence, etiology, diagnosis of
      primary and secondary lactose intolerance (LI), including age of onset, among
      children 1-5 years of age. Suspected/perceived lactose intolerance can lead to
      dietary restrictions which may increase risk of future health issues. METHODS AND
      STUDY DESIGN: MEDLINE, CAB Abstract, and Embase were searched for articles
      published from January 1995-June 2015 related to lactose intolerance in young
      children. Authors independently screened titles/abstracts, full text articles,
      for eligibility against a priori inclusion/exclusion criteria. Two reviewers
      extracted data and assessed quality of the included studies. RESULTS: The search
      identified 579 articles; 20 studies, the majority of which were crosssectional,
      were included in the qualitative synthesis. Few studies reported prevalence of
      primary LI in children aged 1-5 years; those that did reported a range between 0
      17.9%. Prevalence of secondary LI was 0-19%. Hydrogen breath test was the most
      common method used to diagnose LI. None of the included studies reported age of
      onset of primary LI. CONCLUSIONS: There is limited recent evidence on the
      prevalence of LI in this age group. The low number of studies and wide range of
      methodologies used to diagnose LI means that comparison and interpretation,
      particularly of geographical trends, is compromised. Current understanding
      appears to rely on data generated in the 1960/70s, with varied qualities of
      evidence. New, high quality studies are necessary to understand the true
      prevalence of LI. This review is registered with the International Prospective
      Register for Systematic Reviews (PROSPERO).

PMID- 29222880
TI  - Consumption and sources of added sugar in Indonesia: a review.
AB  - BACKGROUND AND OBJECTIVES: The present report summarized the best available
      evidence regarding consumption level and sources of free or added sugars in
      Indonesia. METHODS AND STUDY DESIGN: Information was extracted from food balance
      sheets, household expenditure surveys, nutrition surveys, published studies,
      unpublished theses/ dissertations, and government reports. RESULTS: A total of 18
      references were obtained, showing varying results. Indonesia's national surveys
      suggested intakes of sugar below 50 grams per day or below 10% of energy intake.
      Published studies suggested higher levels of intake. Studies used expenditure
      surveys or a single day of recall to determine dietary intake. None made use of
      biomarkers to determine the level of sugar intake. The 2014 Total Diet Study
      estimated that 11.8% of the population consumed >50 grams sugar per day. Common
      food sources were table sugar, wheat products, milk products, sweetened drinks,
      condiments, candies and chocolate products. CONCLUSIONS: Insufficient evidence
      exists regarding the levels and sources of added sugar intake of different
      population groups in Indonesia. A nationwide survey using multiple (at least two)
      24-hour recalls to allow estimation of usual intake and to identify food sources,
      and the use of biomarkers to validate intake will provide more accurate
      information on which to base policy decisions.

PMID- 29222881
TI  - Development and validation of a pediatric nutritional screening score (PNSS) for
      hospitalized children.
AB  - BACKGROUND AND OBJECTIVES: There is no evidence on the most effective nutritional
      screening tool for hospitalized children. The objective of this study was to
      develop and validate a pediatric nutritional screening tool to assess
      undernutrition risk upon hospital admission. METHODS AND STUDY DESIGN: The study
      had a two-phase prospective observational design. A novel pediatric nutritional
      screening score (PNSS) was developed and sensitivity, specificity, and
      reliability were evaluated by comparing with a complete dietetic assessment.
      Length of hospital stay, weight loss, disease complications, and nutritional
      support were recorded. RESULTS: PNSS consisted of three elements: disease with
      malnutrition risks, changes in food intake, and anthropometric measurements, with
      a score of 0-2 for each element. The optimal cut-off score to identify patients
      (n=96) at risk of undernutrition was two. The agreement between PNSS and the
      complete dietetic assessment was moderate (kappa=0.435, 95% CI=0.373-0.498).
      Sensitivity and specificity values of PNSS were 82% (95% CI=76%-87%) and 71% (95%
      CI=67%-74%), respectively. Inter-rater agreement had a kappa value of 0.596 (95%
      CI=0.529-0.664, p<0.001). The percentage of children with undernutrition risk was
      44.9%. Children with oncologic, gastrointestinal, and cardiac diseases were most
      likely to be at risk of undernutrition. The at-risk group was associated
      significantly with longer length of hospital stay and higher percentage of weight
      loss compared with the not-at-risk group. CONCLUSION: PNSS is the first
      nutritional screening tool developed for hospitalized children and validated in a
      large population of patients in China.

PMID- 29222882
TI  - Relative validity of an indirect calorimetry device for measuring resting energy
      expenditure and respiratory quotient.
AB  - BACKGROUND AND OBJECTIVES: Resting energy expenditure (REE) and respiratory
      quotient (RQ) are important for optimal nutritional care. The purpose of this
      study was to assess the accuracy and repeatability of an indirect calorimetry
      device (IIM-IC-100) in the measurement of REE and RQ in healthy Chinese adults.
      METHODS AND STUDY DESIGN: A total of 38 healthy adults (19 male and 19 female)
      aged 18-52 years (25+/-6 years) were enrolled in this study. REE and RQ were
      measured by IIM-IC-100 and by VO2000, alternately and in duplicate. RESULTS:
      There was a highly significant correlation between IIM-IC-100 REE and VO2000 REE
      (r=0.906, p<0.001), with mean IIM-IC-100 REE significantly higher than that of
      VO2000 (1475+/-269 vs 1394+/-313 kcal/d, p=0.002). Bland- Altman analysis
      revealed that the mean difference between IIM-IC-100 REE and VO2000 REE was 81.3
      kcal/d, with limits of agreement of -185 to +347 kcal/d. There was no significant
      difference in RQ between the two devices. No significant differences were
      observed between the repeated measurements for both devices. Intrasubject
      coefficients of variation (CVs) of REE were smaller for IIM-IC-100 (5.8%) than
      for VO2000 (10.5%), while CVs of RQ were similar for IIM-IC-100 (7.2%) and VO2000
      (6.9%). CONCLUSIONS: These preliminary data indicated that the IIM-IC-100 showed
      promise as an accurate and precise tool in the assessment of REE and RQ in
      healthy Chinese adults.

PMID- 29222883
TI  - The Geriatric Nutritional Risk Index predicts mortality in nonagenarians and
      centenarians receiving home care.
AB  - BACKGROUND AND OBJECTIVES: The increasing prevalence of malnutrition in old
      people is related to the risk of illness and death. A number of screening tools
      to detect malnutrition have been used in the elderly to assess nutritional status
      and predict prognosis. The aim of the present study was to investigate the
      ability of the Geriatric Nutritional Risk Index (GNRI) to assess nutritional
      status and predict mortality in very old home-care people by using a cross
      sectional study of Chinese older people aged 90-105 years. METHODS AND STUDY
      DESIGN: The present study was based on a 4-year follow-up of mortality data from
      a previous cross-sectional study. The study was conducted with a very elderly
      population with a mean age of 93.5+/-3.2 years (n=716; 230 men and 486 women). In
      2005, trained researchers performed face-to-face interviews and physical and
      geriatric assessments to obtain information on sociodemographic factors, self
      reported medical diseases, geriatric-specific conditions, anthropometric factors,
      biochemical data, and the GNRI score. In 2009, vital status were requested from
      the local government. RESULTS: After 4 years of follow-up, 371 participants died
      (125 men and 246 women, 51.8%). The median follow-up time was significantly worse
      in the nutritional risk group (GNRI <=98) (30.26+/-15.80 vs 42.27+/-11.82 months,
      p<0.001). Activities of daily living (ADL) impairment (hazard ratio [HR]=1.414,
      95% CI=1.121-1.783), and GNRI score (HR=0.92, 95% CI=0.908-0.932) were associated
      with all-cause mortality according to a Cox regression analysis. CONCLUSIONS: The
      GNRI, a nutrition-related risk index, can predict mortality in very old Chinese
      home-care people.

PMID- 29222884
TI  - Development and evaluation of nutritional, sensory and glycemic properties of
      finger millet (Eleusine coracana L.) based food products.
AB  - BACKGROUND AND OBJECTIVES: Finger millet (Eleusine coracana L.) (FM) is rich in
      dietary fibre and is therefore expected to elicit a lower glycemic response
      compared to other grains. However, there is little data on the glycemic
      properties of FM-based products. We evaluated the nutritional, sensory and
      glycemic properties of decorticated millet with lower polish (DFM-LDP), flakes
      (FMF), vermicelli (FMV) and extruded snack (FMES) (both FMV and FMES with 7-8%
      added soluble fibre). METHODS AND STUDY DESIGN: The nutrient contents of the FM
      products were evaluated by standard AOAC (Association of Official Analytical
      Chemists) and AACC (American Association of Cereal Chemists) methods. Sensory
      evaluation was conducted monadically using a 9-point hedonic scale using
      untrained panel members. GI testing was conducted using a standardized validated
      protocol. The study was conducted according to the guidelines laid down by the
      Declaration of Helsinki, and was approved by the Ethics Committee of the Madras
      Diabetes Research Foundation. RESULTS: The products had dietary fibre (DF)
      content between 5.8-15.6 g%. FMES was unique in having a very low fat content
      (0.17%). Evaluation of sensory perception revealed moderate acceptance of millet
      based products. The glycemic indices (GI) (mean+/-SEM) of the products were
      84.7+/-7.7%, 82.3+/-6.4%, 65.5+/-5.1% and 65.0+/-6.6% for DFM-LDP, FMF, FMV and
      FMES respectively. CONCLUSIONS: DFM-LDP and FMF (purely finger millet based
      products) elicited higher glycemic responses. Comparatively, FMV and FMES (with
      added functional ingredients) exhibited medium GI values and, are healthier
      dietary options. It is possible to prepare FM products with lower GI by utilizing
      functional ingredients.

PMID- 29222885
TI  - Chronic low grade inflammation measured by dietary inflammatory index and its
      association with obesity among school teachers in Yangon, Myanmar.
AB  - BACKGROUND AND OBJECTIVES: This study was aimed to investigate the association
      between obesity and chronic low grade inflammation (CLGI) measured by Dietary
      Inflammatory Index (DII) as a proxy indicator of CLGI among obese and non-obese
      teachers. METHODS AND STUDY DESIGN: We conducted a cross sectional study among
      128 non-obese (BMI <25) and 116 obese (BMI >=25) female teachers aged 25-60 years
      from six urban schools in Yangon, Myanmar between January and March 2015. Usual
      dietary intake was collected by 3-day nonconsecutive estimated 24 hour's dietary
      records and semi-quantitative Food Frequency Questionnaires. Adapted DII was
      calculated by standardized methods using literature-derived population-based
      dietary inflammatory weights of 31 food parameters. C-reactive protein (CRP) was
      analysed by a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) technique. Mean
      DII between obese and non-obese was compared by independent t test. The
      association between obesity indices and high DII (DII >=1.1) and high CRP (>3
      mg/L) were investigated by logistic regression. RESULTS: Obese teachers had lower
      intakes of anti-inflammatory nutrients (vitamin B-6, vitamin A and zinc)/food
      (onion) compared with non-obese teachers (p<0.05) and obesity was significantly
      associated with CRP (Odd ratio (OR)=5.5, 95% Confidence interval (CI) 1.2-24.1,
      p=0.02). However, there was no significant association between obesity and DII
      (OR=1.4, 95% CI -0.8-2.3, p=0.23). CONCLUSIONS: Role of antiinflammatory foods
      should be promoted for prevention of obesity and related diseases. Further use of
      DII among Myanmar general population for prevention of obesity and its related
      diseases should be explored with longitudinal studies.

PMID- 29222886
TI  - Salivary cariogenic bacteria counts are associated with obesity in student women
      at a Malaysian university.
AB  - BACKGROUND AND OBJECTIVES: The counts of cariogenic bacteria lactobacilli and
      mutans streptococci have been studied and correlated with sugar intake. This
      study was to investigate the association between salivary lactobacilli and mutans
      streptococci counts with sweet food eating behavior and sweet sensitivity among
      120 Malaysian women (101 ethnic Chinese, 19 ethnic Indians), while taking into
      account anthropometric and menstruation variables. METHODS AND STUDY DESIGN:
      Demographics, anthropometric measurements and menstrual history were taken.
      Hedonic preference, intake frequency of a list of sweet foods, intensity
      perception and pleasantness ratings of sweet stimuli were assessed. Saliva was
      collected for lactobacilli and mutans streptococci culture. RESULTS: We found
      that centrally obese subjects (high waist circumference and waist-hip ratio) had
      significantly higher salivary lactobacilli and mutans streptococci counts (all
      p<0.05), while overweight and high total body fat subjects had significantly
      higher salivary mutans streptococci counts (p<0.001). The sweetness intensity
      perception of chocolate malt drinks was significantly lower in women who were in
      their pre-menstrual (post-ovulation) phase. However, menstruation variables
      (menstrual phases, regularity and pre-menstrual syndromes) did not play a role in
      determining compulsive eating, sweets/chocolate craving and salivary lactobacilli
      and mutans streptococci counts. CONCLUSIONS: Taken together, salivary
      lactobacilli and mutans streptococci counts of the Malaysian women are associated
      with central obesity, but not sweet food eating behaviour, sweet sensitivity and
      menstruation variables. Salivary microbiome analysis could be useful as a
      potential diagnostic indicator of diseases such as obesity.

PMID- 29222887
TI  - Relationship between umami taste acuity with sweet or bitter taste acuity and
      food selection in Japanese women university students.
AB  - BACKGROUND AND OBJECTIVES: Although there are many studies on the umami receptor
      and its signaling pathway, literature on the effect of umami taste acuity on
      dietary choices in healthy subjects is limited. The current study aims to clarify
      the relationship between umami taste acuity with sweet or bitter taste acuity,
      food preference and intake. METHODS AND STUDY DESIGN: Forty-two healthy Japanese
      female university students were enrolled. The acuity for umami, sweet, and bitter
      tastes was evaluated using the filter-paper disc method. The study population was
      divided into 32 umami normal tasters and 10 hypo-tasters based on the taste
      acuity at the posterior part of the tongue using monosodium glutamate. RESULTS:
      Umami hypo-tasters exhibited a significantly lower sensitivity to sweet tastes
      than normal tasters. However, the sensitivity to bitter taste was comparable
      between the two groups. Food preference was examined by the food preference
      checklist consisted of 81 food items. Among them, umami tasters preferred
      shellfish, tomato, carrot, milk, low fat milk, cheese, dried shiitake, and kombu
      significantly more than umami hypo-tasters did. A self-reported food frequency
      questionnaire revealed no significant differences in the intake of calories and
      three macronutrients between the two groups; however, umami tasters were found to
      eat more seaweeds and less sugar than umami hypo-tasters. CONCLUSIONS: These data
      together may indicate the possibility that umami taste acuity has an effect on a
      dietary life. Therefore, training umami taste acuity from early childhood is
      important for a healthy diet later in life.

PMID- 29222888
TI  - Common food antimicrobials: effects on cellular inflammation and oxidative damage
      and their estimated occurrence in Singapore.
AB  - BACKGROUND AND OBJECTIVES: The prevalence and potential health effects of common
      food antimicrobials in processed foods and beverages are relatively unknown in
      Singapore. The occurrence of chemical antimicrobials in processed foods and
      beverages and their effects on inflammation and oxidative stress in vitro were
      examined. METHODS AND STUDY DESIGN: The occurrence of antimicrobials in 1605
      processed food and 359 beverage items were examined by surveying the ingredients
      on the product labels. Human neutrophils were exposed to physiologically relevant
      concentrations of common antimicrobials. Established markers of inflammation, l
      Leukotriene B4 and oxidative stress, F2-isoprostanes were measured using stable
      isotope dilution gas chromatography-mass spectrometry. RESULTS: Antimicrobials
      were added to 23.2% of the processed foods and beverages. Sorbic, benzoic,
      lactic, propionic and acetic acids accounted for 84.8% of the added
      antimicrobials in the processed foods and beverages. 92.5% of the bread contained
      propionic acid. Lactic acid was the most common antimicrobial (44.4%) in cheeses.
      Sorbic acid was added to 63.2% of the margarines selected. Sauces (31.5%), energy
      drinks (50.0%), soft drinks (70.7%) and fruit cordials (66.6%) contained added
      benzoic acid. Benzoic and propionic acids at physiologically relevant
      concentrations augmented leukotriene B4formation (benzoicacid, EC50 = ~100 MUg L
      1and propionic acid, >200 MUg L-1). Lactic and sorbic acids dose-dependently
      inhibited the F2-isoprostanes production (IC50 values ~100 MUg L-1) and
      myeloperoxidase activity (IC50values ~100 MUg L-1). CONCLUSIONS: Our results
      demonstrate that Singapore consumers are significantly exposed to food
      antimicrobials, and these molecules, in physiologically relevant concentrations,
      exert significant and differential effects in vitro.

PMID- 29222889
TI  - Effects of parenteral omega-3 fatty acid supplementation in postoperative
      gastrointestinal cancer on immune function and length of hospital stay: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Omega-3 fatty acids are widely used in nutritional
      support. However, whether parenteral supplementation with omega-3 fatty acids is
      effective for gastrointestinal cancer patients remains uncertain. This study
      assessed the effects of this form of parenteral nutrition on immune function and
      clinical outcomes in postoperative gastrointestinal cancer patients. METHODS AND
      STUDY DESIGN: We searched Medline, Embase, Scopus, and the reference lists of
      selected studies to identify randomized controlled trials that compared omega-3
      fatty acids with a control, and that included immune indices, infectious
      complications, or length of hospital stay in the final outcomes. The odds ratio
      and weighted mean difference with 95% confidence intervals were calculated and
      the I2 statistic was used to assess heterogeneity. RESULTS: Seven trials with a
      total of 457 participants were included in the meta-analysis. Five pooled trials
      with 373 participants indicated that the incidence of infectious complications
      was significantly different between the intervention and control groups (odds
      ratio: 0.36; 95% confidence interval: 0.18, 0.74, p<0.05). Five trials involving
      385 participants indicated that parenteral omega-3 fatty acid supplementation
      significantly shortened the length of hospital stay (weighted mean difference: 
      2.29, 95% confidence interval: -3.64, -0.93; p<0.05). Meta-analysis also
      indicated that omega-3 fatty acids increased the level of CD4+ and CD4+/CD8+
      ratio. CONCLUSIONS: The results of this study suggest that parenteral omega-3
      fatty acid supplementation is beneficial for gastrointestinal cancer patients,
      and is accompanied by improved postoperative immune function and satisfactory
      clinical outcomes.

PMID- 29222890
TI  - Home enteral nutrition after minimally invasive esophagectomy can improve quality
      of life and reduce the risk of malnutrition.
AB  - BACKGROUND AND OBJECTIVES: The potential benefits of home enteral nutrition (HEN)
      and the effects of HEN on quality of life (QOL) after esophagectomy remain
      unclear. The aim was to investigate the effect of 3 months HEN on health related
      QOL and nutritional status of esophageal cancer patients who were preoperatively
      malnourished. METHODS AND STUDY DESIGN: 142 malnourished (PG-SGA stage B or C)
      patients with esophageal cancer were assigned to receive Ivor Lewis minimally
      invasive esophagectomy (MIE group) with laparoscopic jejunal feeding tube
      placement or open esophagectomy (OE group) with nasojejunal feeding tube
      placement. After discharge, patients in the MIE group received HEN with 500-1000
      kcal/d for 3 months, while the OE group patients did not receive HEN, as
      nasojejunal feeding tubes had been removed. QLQ-C30 and PG-SGA questionnaires
      were used to evaluate the QOL and the risk of malnutrition. RESULTS: 67 patients
      were enrolled in the MIE group and 75 patients were enrolled in the OE group.
      Symptoms related to fatigue, nausea, vomiting, pain, and appetite loss were
      significantly decreased in the patients treated with 3 months HEN. Similarly,
      patients treated with 3 months HEN had a lower risk of malnutrition than patients
      did not receive HEN (PG-SGA score, 5.7 vs 7.9, p<0.01). More patients in the MIE
      group (received 3 months HEN) were able to complete postoperative
      chemoradiotherapy than patients in the OE group (p<0.01). CONCLUSIONS: MIE and
      subsequent treatment with 3 months HEN can improve the QOL and reduce the risk of
      malnutrition in preoperatively malnourished patients.

PMID- 29222891
TI  - Effects of preoperative oral carbohydrate therapy on perioperative glucose
      metabolism during oral- maxillofacial surgery: randomised clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Preoperative oral carbohydrate therapy has been
      suggested to attenuate postoperative insulin resistance. The purpose of this
      study was to investigate the effect of a carbohydrate-rich beverage given
      preoperatively on intraoperative glucose metabolism. METHODS AND STUDY DESIGN:
      This study was a randomised, open-label, placebo-controlled trial. Patients
      undergoing oral-maxillofacial surgery were divided into two groups. In the
      glucose group, patients took glucose (50 g/278 mL, p.o.) 2 h before anaesthesia
      induction after overnight fasting; control-group patients took mineral water.
      Primary outcome was blood concentrations of ketone bodies (KBs); secondary
      outcomes were blood concentrations of free fatty acids, insulin and glucose.
      Concentrations were measured 2 h before anaesthesia (T0), induction of
      anaesthesia (T1), and 1 h (T2), 3 h (T3), and 5h after anaesthesia start (T4).
      RESULTS: In the control group (n=11), KBs increased continuously from anaesthesia
      induction. In the glucose group (n=12), KBs were maintained at low concentrations
      for 3h after beverage consumption but increased remarkably at T3. At T1 and T2,
      concentrations of KBs in the glucose group were significantly lower than those in
      the control group (T1, p=0.010; T2, p=0.028). In the glucose group, glucose
      concentrations decreased significantly at T2 temporarily, but in the control
      group, glucose concentrations were stable during this study (T2, p<0.001: glucose
      vs control). CONCLUSIONS: Preoperative intake of glucose (50 g, p.o.) can
      alleviate ketogenesis for 3 h after consumption but can cause temporary
      hypoglycaemia after anaesthesia induction.

PMID- 29222892
TI  - Benefit of oral nutritional supplements for children with acute lymphoblastic
      leukaemia during remission-induction chemotherapy: a quasi-experimental study.
AB  - BACKGROUND AND OBJECTIVES: To determine the effect of oral nutritional
      supplements (ONS) on children with acute lymphoblastic leukaemia undergoing
      remission-induction chemotherapy. METHODS AND STUDY DESIGN: We included 127
      paediatric patients who were diagnosed with acute lymphoblastic leukaemia and
      undergoing remission- induction chemotherapy in the First Affiliated Hospital of
      Zhengzhou University. Children from two paediatric wards who met the inclusion
      criteria were enrolled. One ward was randomly chosen as the intervention group
      and the other ward as the control group. Children in the two groups were matched
      for age and sex. The ONS group was administered Peptamen(r) (n=60) and the
      control group was administered a low-fat diet (n=67). RESULTS: The baseline
      information before treatment was not significantly different between groups
      (p>0.05). In the control group, weight loss at the end of chemotherapy was
      significantly higher than that of ONS group (p<0.05). The hemoglobin level and
      the concentrations of total protein, albumin, and pre-albumin were significantly
      higher in the ONS group than in the control group (p<0.05 and p<0.01,
      respectively). The incidences of hypoalbuminaemia, gastrointestinal
      complications, and infection were lower in the ONS group than in the control
      group (p<0.05). The ONS group also used lower amount of albumin infusion, fewer
      blood-product infusion, and had lower hospital costs than the control group.
      CONCLUSIONS: During remission-induction chemotherapy, oral nutritional
      supplements can improve the nutritional status of children, reduce the incidence
      of complications, and decrease the costs of hospitalization.

PMID- 29222893
TI  - Postprandial long-chain n-3 polyunsaturated fatty acid response to krill oil and
      fish oil consumption in healthy women: a randomised controlled, single-dose,
      crossover study.
AB  - BACKGROUND AND OBJECTIVES: Krill oil (KO) and fish oil (FO) are good sources of
      health-benefiting long chain n- 3 polyunsaturated fatty acids (LC n-3 PUFA), EPA
      and DHA. There are conflicting outcomes on the bioavailability of LC n-3 PUFA
      from KO compared with FO. This study investigated the postprandial incorporation
      of LC n- 3 PUFA into plasma lipids following consumption of 5 capsules of KO or
      FO in comparison with olive oil (OO) control in healthy women. METHODS AND STUDY
      DESIGN: 10 women (aged 18-45 years) consumed a high-fat (15 g) breakfast,
      supplemented with 5 g of KO, FO, or OO in a random order with a minimum seven-day
      washout period between the supplementations. The LC n-3 PUFA content in KO was
      907 mg compared with 1441 mg in FO. Blood samples were collected in the fasting
      state and for the next 5 hours after test meal consumption on an hourly basis.
      RESULTS: Significant increases in plasma EPA concentrations were observed
      starting at 2 h after KO and FO consumption (p<0.05). There were no significant
      changes in either DHA or DPA between the three groups. The increases in plasma
      EPA concentrations were similar between the KO and FO groups (p>0.05).
      CONCLUSIONS: The lower dose (31%) of EPA from KO led to a similar plasma EPA
      concentration as in the FO group, suggesting that EPA from KO may be more
      efficiently incorporated into plasma. This may be related to the high content of
      phospholipids and free fatty acids in KO.

PMID- 29222894
TI  - International hospital accreditation and clinical nutrition service in acute care
      hospitals in South Korea: results of a nationwide cross-sectional survey.
AB  - BACKGROUND AND OBJECTIVES: Beginning in 2007, 29 hospitals in South Korea have
      received accreditation from Joint Commission International (JCI). The present
      study aimed to identify differences in clinical nutrition service provisions
      between JCI accredited acute care hospitals and non-accredited acute care
      hospitals. A survey questionnaire was sent to all 43 acute care hospitals in
      South Korea. METHODS: A total of 35 sets of clinical nutrition service surveys,
      234 sets of clinical dietitian job satisfaction surveys, and five-day daily work
      logs from 129 clinical dietitians were received. We used Fisher's exact test and
      independent t-test to analyze differences between acute care hospitals based on
      JCI accreditation. STUDY DESIGN: Nationwide cross-sectional survey. RESULTS: JCI
      accredited acute care hospitals (N=8) showed a higher, but not significantly
      higher, nutritional intervention rate of 12.7% among malnourished patients,
      compared with 7.0% in non-JCI accredited acute care hospitals (N=27). Analysis of
      work hours of clinical dietitians indicated time spent on direct care was higher
      (p<0.05), while time spent on outpatient care was lower (p<0.05) among JCI
      accredited acute care hospitals relative to non-JCI accredited acute care
      hospitals. CONCLUSIONS: Accreditation from JCI has a positive influence in the
      advancement of not only the hospital services, but also clinical nutrition
      services.

PMID- 29222895
TI  - Sarcopenia and cachexia evaluation in different healthcare settings: a
      questionnaire survey of health professionals.
AB  - BACKGROUND AND OBJECTIVES: The rates of sarcopenia and cachexia evaluations by
      different occupational groups at different settings are unclear. The objectives
      are to evaluate and compare the relative use of sarcopenia and cachexia
      evaluations among dietitians and associated healthcare professionals in a diverse
      range of settings. METHODS AND STUDY DESIGN: Participants were 4,621 members from
      the Japanese Association of Rehabilitation Nutrition. Settings included acute
      general wards, convalescent rehabilitation wards, long-term care wards, homecare
      service, and other settings. A questionnaire-based cross-sectional study was
      performed to evaluate assessments for sarcopenia and cachexia among dietitians
      and other professionals. Multiple comparisons based on Bonferroni method and
      logistic regression analysis were used. RESULTS: 718 (15.5%) answered the
      questionnaire. Data from 683 valid questionnaires were analyzed. Muscle strength,
      muscle mass, physical function, and cachexia were assessed by 53.4%, 51.1%,
      53.4%, and 17.4% of dietitians. At convalescent rehabilitation wards, these rates
      were 81.8%, 62.0%, 82.5%, and 14.0%. The use of muscle strength and physical
      function evaluations was significantly lower among dietitians than among physical
      therapists and occupational therapists. The use of muscle mass and cachexia
      evaluations was not significantly different among the occupations. The use of
      muscle mass and strength evaluations was significantly higher in convalescent
      rehabilitation wards than in acute general wards, long-term care wards and
      facilities, and other settings, but not in homecare services. Cachexia
      evaluations were not significantly different between all settings. CONCLUSIONS:
      Raising the awareness of cachexia and sarcopenia among dietitians is a key issue,
      which should be addressed.

PMID- 29222896
TI  - Serum vitamin B-12 in children presenting with vasovagal syncope.
AB  - BACKGROUND AND OBJECTIVES: The present study aims to determine the serum vitamin
      B-12 in children presenting with vasovagal syncope. METHODS AND STUDY DESIGN:
      This is a prospective review of 160 children presenting with vasovagal syncope.
      Subgroup analysis was done based on the results of head up tilt test. RESULTS:
      Head up tilt test gave positive results in 80 children and yielded negative
      results in the remaining 80 children. The tilt test positive children had
      significantly lower thyroid stimulating hormone concentrations (p=0.06), total
      iron binding capacity (p=0.04) and serum vitamin B-12 (p=0.01). The prevalence of
      vitamin B-12 deficiency was significantly higher in the tilt positive group (80%
      vs 52.5%, p=0.001). Out of 80 children with positive tilt test, 8 children (10%)
      showed cardioinhibitory response, 22 children (27.5%) demonstrated a
      vasodepressor response, 24 children (30%) displayed mixed response and 26
      children (32.5%) had the postural orthostatic tachycardia syndrome. Erythrocyte
      sedimentation rate was significantly lower in the mixed response group than in
      the vasodepressor group (6.2+/-0.8 mm/h vs 14.3+/-2.5 mm/h, p=0.001). Serum
      vitamin B-12 was significantly lower in the postural orthostatic tachycardia
      syndrome (POTS) group than in the vasodepressor group (240.8+/-38.2 pg/mL vs
      392.7+/-27.1 pg/mL, p=0.001). The prevalence of vitamin B-12 deficiency was
      significantly higher in the POTS group than in the vasodepressor group (92.3% vs
      45.5%, p=0.001). CONCLUSIONS: Vitamin B-12 deficiency causes reduction in
      myelinization, deceleration in nerve conduction and elevation in serum
      concentrations of noradrenaline. These factors may contribute to the impairment
      of autonomic functions which are involved in the pathogenesis of vasovagal
      syncope.

PMID- 29222897
TI  - Platelet-related cytokines among normal body mass index, overweight, and obese
      Malaysians.
AB  - BACKGROUND AND OBJECTIVES: Recent studies have reported that obesity is
      associated with platelet activation and systemic inflammation. Malaysia has the
      highest prevalence of obesity, hence, this research is performed to evaluate the
      development of low-grade inflammation and platelet activation, measured using
      soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel), and to determine
      their association with obesity. In addition, we assessed the mean platelet volume
      (MPV) and platelet count (PLT), which are novel parameters consistently
      associated with obesity. METHODS AND STUDY DESIGN: A cross-sectional study was
      conducted on 112 healthy men and women from 3 main ethnic group (Malay, Chinese,
      and Indian) who were aged 18-60 years. The participants were categorized into
      normal body mass index (BMI), overweight and obese groups according to WHO
      criteria for BMI in Asian populations (18.5 kg/m2<BMI<35 kg/m2). Waist
      circumference (WC) was also measured and included in the analysis. RESULTS: MPV,
      sCD40L, and sP-sel differed significantly among the normal BMI, overweight, and
      obese groups (p<0.05). Contrastingly, the PLT did not vary significantly among
      the 3 groups. In addition, sP-sel levels correlated significantly with BMI
      (r=0.36, p=0.001) and WC (r=0.25, p=0.007) and MPV correlated significantly with
      BMI (r=0.2, p=0.001) and WC (r=0.2, p=0.003). CONCLUSIONS: Higher MPV and sPsel
      levels in the obese participants than in the overweight and normal BMI
      participants indicated potentially higher activation of platelets in people with
      obesity. Moreover, we observed higher sCD40L levels in obese participants than in
      the overweight and normal BMI participants, suggesting a proinflammatory state in
      obese individuals.

PMID- 29222898
TI  - Exercise induced dehydration status and skinfold compressibility in athletes: an
      intervention study.
AB  - BACKGROUND AND OBJECTIVES: Skinfold thickness assessment is a widely recognized
      technique for the estimation of body adiposity and fat free mass. This method
      assumes that skinfolds' compressibility is constant but there are some factors
      that could influence its compressibility. This study aims to evaluate whether the
      skinfolds' compressibility is influenced by hydration status. METHODS AND STUDY
      DESIGN: An intervention study was conducted in a sample of 22 adult male amateur
      soccer players, who took part in a 90min simulated soccer match. Before and after
      the intervention skinfolds thicknesses were measured in eight anatomical sites.
      An electronic caliper, Lipotool, was used to collect and record 120 values during
      2s of evaluation. To analyze skinfolds' compressibility, two methods were used:
      identification of lowest skinfold thickness measurement (SL) and SH = 110% x SL,
      and the parameter TAU (tau) determination. Baseline hydration status was
      evaluated by total body water (TBW) through multifrequency bioimpedance analysis.
      Dehydration was assessed by the difference of body weight before and after the
      intervention. RESULTS: The intervention resulted in a loss of 2.11% of
      participants' baseline weight. The skinfolds thicknesses, assessed by SL and SH,
      were significantly higher after exercise for all skinfolds except for skinfolds
      at iliac crest and abdominal. This intervention did not affect skinfolds'
      compressibility when assessed by tau. However, an association between dehydration
      and medial-calf skinfold' compressibility was found (r=0.48, p=0.042).
      CONCLUSIONS: Although an increase in the skinfolds thickness after the
      intervention was found, skinfolds' compressibility did not change.

PMID- 29222899
TI  - Prevalence and determinants of iron deficiency anemia among non-pregnant women of
      reproductive age in Pakistan.
AB  - BACKGROUND AND OBJECTIVES: Iron deficiency Anemia (IDA) in women of reproductive
      age is a recognized public health concern that impairs health and well-being in
      women and is associated with adverse reproductive outcomes. In Pakistan there is
      a dearth of up-to-date information on the prevalence and predictors of IDA. This
      study sought to investigate IDA in Pakistani women. METHODS AND STUDY DESIGN:
      Secondary analysis was performed using the National Nutrition Survey in Pakistan
      2011- 2012. We used a pre-structured instrument to collect socio demographic,
      reproductive and nutritional data on women. We also collected anthropometric
      measurements and blood samples for micronutrient deficiencies. Univariate and
      multivariate logistic regression were used to analyse the data. RESULTS: A total
      of 7491 non-pregnant women aged between 15-49 years were included in the
      analysis. The prevalence of IDA was 18.1%. In the multivariate regression
      analysis; not using iron folic acid supplementation during the last pregnancy
      adjusted odds ratio (AOR) (95% CI) 1.31 (1.05, 1.64), a history of four or more
      pregnancies AOR (95% CI) 1.30 (1.04, 1.60), birth interval of <24 months AOR (95%
      CI) 1.27 (1.06, 1.71), household food insecurity AOR (95% CI) 1.42 (1.23, 1.63)
      and presence of clinical anemia AOR (95% CI) 5.82 (4.82, 7.02) were significantly
      associated with increased odds of IDA while with obesity AOR (95% CI) 0.60 (0.4,
      0.88) showed a protective effect on IDA. CONCLUSION: To reduce IDA in Pakistani
      women, the country needs a multifaceted approach that incorporates iron
      supplementation, food fortification, improved family planning services and
      efforts to reduce food insecurity.

PMID- 29222900
TI  - Comparisons of proteomic profiles of whey protein between donor human milk
      collected earlier than 3 months and 6 months after delivery.
AB  - BACKGROUND AND OBJECTIVES: Human milk has nutritional, protective, and
      developmental advantages for premature infants. However, proteomic information of
      low abundant protein of donor milk is insufficient. The purpose of this study is
      to analyze and compare the proteome of low abundant protein of donor milk
      obtained at different postpartum ages other than the colostrum. METHODS AND STUDY
      DESIGN: Donor breast milk from 12 healthy mothers was collected 15 days, 2 months
      and 6 months after delivery and stored by medically approved methods. The whey
      milk proteomes were analyzed by mass spectrometry and classified using
      bioinformatics analysis. RESULTS: Human milk obtained 15 days and 2 months after
      delivery showed more abundant expression of whey proteins related to the
      generation of precursor metabolites and energy, metabolism, and catalytic
      activity, compared with milk collected at 3 months. Immune and transport-related
      proteins were abundant at all time points. Proteins involved in cellular
      movement, immune cell trafficking, and the carbohydrate metabolism network was
      more abundant in whey milk collected at 15 day and 2 months using a network
      analysis. CONCLUSIONS: We report proteomic information for human donor whey
      protein. As significant changes were found in whey proteome collected earlier
      than 2 months and 6 months after delivery, selecting human donor milk earlier
      than 2 months might be more helpful for early postnatal recipients.

PMID- 29222901
TI  - Association of energy intake and physical activity with overweight among
      Indonesian children 6-12 years of age.
AB  - BACKGROUND AND OBJECTIVES: Indonesia is currently facing double burden
      malnutrition in children. As overweight and obesity are due to a disturbed energy
      balance, this study aimed to assess the association of total energy intake and
      physical activity with the prevalence of overweight among Indonesian children.
      METHODS AND STUDY DESIGN: The data used for this analysis were from 1143
      children, 6-12 years old, that participated in the South East Asian Nutrition
      Survey (SEANUTS). Physical activity (PA) was measured using pedometers for 2
      consecutive days and was categorized low, moderate and high. Child nutritional
      status was categorized based on body mass index for age z-scores (BAZ) into
      normal weight (-2 SD <=BAZ<=1 SD) or overweight (BAZ >1 SD). Energy intake was
      calculated from a one day 24 hour recall and compared to the Indonesian
      recommended dietary allowance (RDA) for energy. RESULTS: Children with low PA had
      higher risk (ODDs 3.4, 95% CI: 2.0, 6.0) of being overweight compared to children
      who had high PA. Children with moderate PA and energy take >100% RDA had higher
      risk (ODDs 4.2, 95% CI 1.9, 9.3) of being overweight than children with high PA
      and energy intakes <=100% RDA. CONCLUSIONS: Low physical activity independently
      or moderate physical activity and high energy intake are risk factors for
      Indonesian children to get overweight. Program intervention such as increasing
      physical activity at school and home is needed to reduce overweight among
      children.

PMID- 29222902
TI  - Fruit and vegetable intake of Korean children and adolescents according to
      cooking location and daily meal: study based on 2010 and 2011 Korea National
      Health and Nutrition Examination Survey data.
AB  - BACKGROUND AND OBJECTIVES: This study analyzed the intake of fruits and
      vegetables by cooking location and daily meals for Korean children and
      adolescents. METHODS AND STUDY DESIGN: For this study, 2,538 Korean children and
      adolescents aged 7-18 years, who participated in the 2010 and 2011 Korea National
      Health and Nutrition Examination Survey dietary intake survey (24-hour recall
      methods), were sampled. RESULTS: The total unsalted fruit and vegetable intake
      for all subjects was 300 g (aged 7-12 years, 280 g; aged 13-18 years, 316 g).
      Regarding meal serving location, the combined unsalted fruit and vegetable intake
      was 159 g at home, 206 g at commercial locations, and 104 g at institutions. The
      combined unsalted fruit and vegetable intake in snack form was 128 g, which was
      higher than that during daily meals. In total, 24.9% of subjects satisfied the
      recommended fruit and vegetable intake (>=400 g), according to the guidelines
      created by the World Health Organization/World Cancer Research Fund. Logistic
      regression analysis results revealed that the fruit and vegetable intake of girls
      was 1.4 times higher than that of boys, and the number of people who ate more
      than 400 g of fruits and vegetables was 1.7 times higher in the group with higher
      education. CONCLUSIONS: Based on the above results, in-depth measures to
      continuously increase intake of fruits and vegetables in children and adolescents
      are needed. This study can be used as basic data for the development of
      educational programs for dietary improvements.

PMID- 29222903
TI  - Vitamin D status and cardiometabolic risk factors in young adults in Hong Kong:
      associations and implications.
AB  - BACKGROUND AND OBJECTIVES: Vitamin D deficiency is reportedly common, but we lack
      data from young adults. Such data are of interest because epidemiological data
      support vitamin D as a possible risk modulator for diabetes and cardiovascular
      ('cardiometabolic') disease. Our objectives were to assess vitamin D status (as
      plasma 25(OH)D concentration) and investigate associations between this and
      biomarkers of cardiometabolic disease risk in a group of still-healthy young
      adults in Hong Kong. METHODS AND STUDY DESIGN: In this observational study,
      fasting venous blood was collected from 196 (63 males, 133 females), young (18-26
      years) non-smoking, nonobese, consenting adults in good general health. Plasma
      25(OH)D was measured by LC-MS/MS. A panel of established cardiometabolic risk
      factors (HbA1c, plasma glucose, lipid profile, hsCRP) and blood pressure were
      also measured. RESULTS: Mean (SD) plasma 25(OH)D concentration was 42.1 (13.0),
      with range 15.7-86.8 nmol/L; 141/196 subjects (72%) had vitamin D deficiency
      (25(OH)D <50 nmol/L); 13/184 (6.6%) were severely deficient (<25 nmol/L). Inverse
      association was seen between 25(OH)D and fasting glucose (r=-0.18; p<0.05).
      Higher HbA1c and TC:HDL-C ratio and lower HDL-C were seen in those with plasma
      25(OH)D <25 nmol/L (p<0.05). CONCLUSIONS: Vitamin D deficiency was highly
      prevalent and associated with poorer cardiometabolic risk profile in these young
      adults. Public health strategies for addressing vitamin D deficiency are needed
      urgently. These new data provide support for further study on vitamin D
      deficiency as a modifiable risk factor for cardiometabolic disease and the
      ameliorative effects of increased vitamin D intake on cardiometabolic disease
      risk profile of vitamin D-deficient young adults.

PMID- 29222904
TI  - Dietary patterns change over two years in early adolescent girls in Hawai'i.
AB  - BACKGROUND AND OBJECTIVES: In investigating diet-disease relationships,
      examination of dietary patterns allows for conclusions to be drawn based on
      overall intake. This study characterized dietary patterns of early adolescent
      girls over a two-year period and examined the relationship between dietary
      patterns and body mass index (BMI). METHODS AND STUDY DESIGN: Cross-sectional
      analyses were performed using longitudinal data from food records of early
      adolescent girls (n=148) 9 to 14 years in Hawai'i from the Female Adolescent
      Maturation (FAM) study. Dietary patterns were identified using principal
      component analysis (PCA). Pearson's correlations between BMI percentile and z
      score and dietary pattern factor scores at Times 1 (2001-2002) and 2 (2002-2003)
      were calculated. For each dietary pattern, participants were divided into low,
      intermediate, and high scorers. Mean BMI percentiles and z-scores were compared
      between groups using analysis of covariance. RESULTS: At Time 1, three patterns
      were identified, characterized by: (1) whole grains, nuts and seeds, added sugar;
      (2) non-whole grain, tomatoes, discretionary fat; and (3) deep yellow vegetables,
      other starchy vegetables, cooked dry beans/peas. At Time 2, three different
      dietary patterns emerged: (1) non-whole grains, meat, discretionary fat; (2)
      other vegetables, fish, eggs; and (3) whole grain, tomatoes, other vegetables.
      BMI percentile and z-score differed between high and low scorers on Time 1
      Pattern 1 and Time 2-Pattern 3. CONCLUSION: Results revealed changes in dietary
      patterns over time and an association between intake and BMI. Findings
      demonstrate the importance of frequent nutrition assessment to monitor changes in
      intake that may be improved to prevent obesity.

PMID- 29222905
TI  - Premorbid dietary intake of protein is associated with early outcomes but not
      with severity of ischemic stroke.
AB  - BACKGROUND AND OBJECTIVES: Dietary protein intake has been associated with
      reduced risk of stroke. This study aimed to examine the relationship between
      premorbid dietary intake of protein and both stroke severity and neurological
      outcomes in patients with acute ischemic stroke. METHODS AND STUDY DESIGN:
      Consecutive patients with first-ever ischemic stroke in Jinling Hospital were
      screened for eligibility of participation. A validated foodfrequency
      questionnaire (FFQ) was performed to collect necessary data for calculating pre
      stroke dietary intakes. Stroke severity was assessed by the National Institutes
      of Health Stroke Scale (NIHSS) at baseline. Neurological outcomes were assessed
      by the modified Rankin scale (mRS) 90 days after stroke onset. Multivariable
      logistical regression was applied to analyze the impacts of dietary protein
      intake on stroke severity or neurological outcomes. RESULTS: Of the 201 enrolled
      patients, 110 (54.7%) were classified as minor (NIHSS <=5) and 91 (45.3%) as
      major stroke (NIHSS >=6). After adjusting for potential confounders,
      multivariable logistic regression did not detect significant association between
      total (odds ratio (OR)=0.98, p=0.15), animal (OR=1.01, p=0.87) or plant protein
      intake (OR=0.96, p=0.07) and stroke severity. According to the 90-day mRS, 127
      patients (63.2%) were determined with good (mRS <=2), and 74 (36.8%) with poor
      outcomes (mR 3-6). Multivariable logistic regression detected that premorbid
      dietary intake of total protein was positively associated with good neurological
      outcomes (OR=1.05, p=0.04). CONCLUSIONS: Higher level of premorbid protein intake
      may be associated with favorable neurological outcomes independent of stroke
      severity.

PMID- 29222906
TI  - Low maternal folate concentrations and maternal MTHFR C677T polymorphism are
      associated with an increased risk for neural tube defects in offspring: a case
      control study among Pakistani case and control mothers.
AB  - BACKGROUND AND OBJECTIVES: There is considerable evidence that periconceptional
      maternal folate deficiency and coding variants in maternal genes coding for
      critical enzymes in the folate pathway are associated with neural tube defects
      (NTDs) in offspring. In a case-control study we investigated C677T polymorphism
      in the 5,10- methylenetetrahydrofolate reductase (MTHFR) gene in case and control
      mothers of Pakistani origin, and compared these with the respective maternal
      folate concentrations measured at the time of delivery. METHODS AND STUDY DESIGN:
      A case-control study was conducted among 109 case and 100 control mothers
      identified through the Holy Family Hospital Rawalpindi, Quaid-i-Azam University,
      Islamabad, Pakistan. Red blood cell (RBC) and serum folate concentrations and
      MTHFRC677T polymorphism were compared between case and control mothers. RESULTS:
      Mean RBC folate and serum folate concentrations were significantly lower in cases
      compared with control mothers (p<0.0001). Maternal MTHFR 677CT and 677TT
      genotypes were more common among cases compared with control mothers (CC vs TT
      p<0.0393 and CC/CT vs TT p<0.021). T-allele frequency was higher in cases
      compared with control mothers (C vs T p<0.017). Case mothers with 677CT or 677TT
      genotypes had significantly lower serum (p<0.0001) and RBC folate concentrations
      (p<0.0001) compared with control mothers. CONCLUSIONS: The present study provides
      further evidence that maternal folate deficiency and MTHFRC677T polymorphism
      might be associated with an increased risk for NTDs in offspring. Our results are
      limited by the fact that maternal folate concentrations were not obtained during
      the periconceptional period, but at delivery. Further analyses, including
      maternal folate levels during the periconceptional period, are warranted.

PMID- 29222907
TI  - The ameliorative effect of fluoxetine on neuroinflammation induced by sleep
      deprivation.
AB  - It is well known that sleep disorders are harmful to people's health and
      performance, and growing evidence suggests that sleep deprivation (SD) can
      trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine
      rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the
      neuroinflammation induced by SD, but the regulatory signaling that governs the
      NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory
      action of antidepressants in astrocytes could affect the neuroinflammation
      induced by SD also remains obscure. In this study, we were the first to discover
      that the antidepressant fluoxetine, a type of specific serotonin reuptake
      inhibitor widely used in clinical practice, could suppress the neuroinflammation
      and neuronal apoptosis induced by SD. The main findings from this study are as
      follows: (i) SD stimulated the expression of activated NLRP3 inflammasomes and
      the maturation of IL-1beta/18 via suppressing the phosphorylation of STAT3 in
      astrocytes; (ii) SD decreased the activation of AKT and stimulated the
      phosphorylation of GSK-3beta, which inhibited the phosphorylation of STAT3; (iii)
      the NLRP3 inflammasome expression stimulated by SD was partly mediated by the
      P2X7 receptor; (iv) an agonist of STAT3 could significantly abolish the
      expression of NLRP3 inflammasomes induced by an agonist of the P2X7 receptor in
      primary cultured astrocytes; (v) the administration of fluoxetine could reverse
      the stimulation of NLRP3 inflammasome expression and function by SD through
      elevating the activation of STAT3. In conclusion, our present research suggests
      the promising possibility that fluoxetine could ameliorate the neuronal
      impairment induced by SD.

PMID- 29222908
TI  - How effective are common household preparations on removing pesticide residues
      from fruit and vegetables? A review.
AB  - Nowadays, the use of pesticides is inevitable for pest control in crops,
      especially for fruit and vegetables. After the harvest from raw agricultural
      commodities, the amount of pesticide residues in food is mainly influenced by the
      storage, handling and processing that follow. If good agricultural and good
      manufacturing practices are enforced effectively, the amount of pesticide
      residues would be brought below the corresponding maximum residue level. Thus,
      the consumption of raw and/or prepared fruit and vegetables would be safe.
      Nonetheless, reports regarding pesticide residues in fruit or vegetables on mass
      media have been worrying consumers, who are concerned about the adverse effects
      of pesticide residues. As a result, consumers perform household processing before
      consumption to reduce any related risks. However, can these preparations
      effectively remove pesticide residues? Reviewing the extensive literature, it
      showed that, in most cases, washing and soaking can only lead to a certain degree
      of reduction in residue level, while other processing such as peeling, soaking in
      chemical baths and blanching can reduce pesticide residues more effectively. In
      general, the behaviour of residues during processing can be rationalised in terms
      of the physico-chemical properties of the pesticide and the nature of the
      process. In contrast, the reported studies are diversified and some areas still
      lack sufficient studies to draw any remarks. Recommendations are provided with
      respect to the available information that aims to formulate an environmental
      friendly, cost-effective and efficient household processing of fruit and
      vegetables to reduce pesticide residues. (c) 2017 Society of Chemical Industry.

PMID- 29222910
TI  - Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and
      Alcohol Consumption in Young Adult Males.
AB  - BACKGROUND: Epigenetic mechanisms are candidate moderators of the effect of
      maltreatment on brain and behavior. Interactions between maltreatment and the
      monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR)
      are associated with alcohol-related problems. However, presently it is not known
      whether DNA methylation moderates this association. The study focused on 53 young
      adult males and aimed to determine whether MAOA methylation moderated the
      association of alcohol-related problems with the interaction of MAOA-uVNTR and
      maltreatment, and whether alcohol consumption moderated the association of MAOA
      methylation with the interaction of MAOA-uVNTR and maltreatment. METHODS: MAOA
      uVNTR genotypes with <= 3 and > 3 repeats were categorized as short (S) and long
      (L), respectively. Data on maltreatment were obtained retrospectively, using self
      reported questionnaires. DNA methylation of 16 candidate CpGs within part of the
      MAOA first exon and intron was assessed and grouped based on principal component
      analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders
      Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C.
      Moderation effects were assessed and probed using the moderated moderation model
      and Johnson-Neyman's method, respectively. RESULTS: Carriers of the S allele, who
      experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in
      the first intron) MAOA methylation levels, reported higher AUDIT score in
      contrast to L-allele carriers. Carriers of the S allele, who reported higher
      AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of
      CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers.
      CONCLUSIONS: Intronic methylation moderated the association of alcohol-related
      problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption
      moderated the association of exonic methylation with the interaction of MAOA
      uVNTR and maltreatment. These results suggest that epigenetic factors as well as
      genotype and maltreatment play a role in the development of alcohol misuse among
      young adult males.

PMID- 29222909
TI  - An emerging role of astrocytes in vascular contributions to cognitive impairment
      and dementia.
AB  - Vascular contributions to cognitive impairment and dementia (VCID) is understood
      to be the second most common cause of dementia after Alzheimer's disease, and is
      also a frequent comorbidity with Alzheimer's disease. While VCID is widely
      acknowledged as a key contributor to dementia, the mechanistic underpinnings of
      VCID remain poorly understood. In this review, we address the potential role of
      astrocytes in the pathophysiology of VCID. The vast majority of the blood vessels
      in the brain are surrounded by astrocytic end-feet. Given that astrocytes make up
      a significant proportion of the cells in the brain, and that astrocytes are
      usually passively connected to one another through gap junctions, we hypothesize
      that astrocytes are key mediators of cognitive impairment because of
      cerebrovascular disease. In this review, we discuss the existing body of
      literature regarding the role of astrocytes at the vasculature in the brain, and
      the known consequences of their dysfunction, as well as our hypotheses regarding
      the role astrocytes play in VCID. This article is part of the Special Issue
      "Vascular Dementia".

PMID- 29222911
TI  - Current and future therapeutic regimens for nonalcoholic fatty liver disease and
      nonalcoholic steatohepatitis.
AB  - : Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic
      steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis,
      hepatocellular carcinoma, and indications for liver transplantation. Other than
      lifestyle modification through diet and exercise, there are currently no other
      approved treatments for NASH/NAFLD. Although weight loss can be effective, it is
      difficult to achieve and sustain. In contrast, bariatric surgery can improve
      metabolic conditions associated with NAFLD, and has been shown to improve liver
      histology. To have approved regimens for the treatment of NASH/NAFLD, several
      issues must be addressed. First, all stakeholders must agree on the most
      appropriate clinical trial endpoints for NASH. Currently, resolution of NASH
      (without worsening fibrosis) or reduction of fibrosis stage (without worsening
      NASH) are the accepted endpoints by the regulatory authorities. It is important
      to recognize the prognostic implication of histologic features of NASH. In this
      context, although histologic NASH has been associated with advanced fibrosis, it
      is not an independent predictor of long-term mortality. In contrast, there are
      significant data to suggest that fibrosis stage is the only robust and
      independent predictor of liver-related mortality. In addition to the primary
      endpoints, several important secondary endpoints, including noninvasive
      biomarkers, long-term outcomes, and patient-reported outcomes must be considered.
      In 2018, a few phase 3 clinical trials for the treatment of NASH have been
      initiated. Additionally, a number of phase 2a and 2b clinical trials targeting
      different pathogenic pathways in NASH are in the pipeline of emerging therapies.
      CONCLUSION: Over the next 5 years, some of these regimens are expected to provide
      potential new treatment options for patients with NASH/NAFLD. (Hepatology
      2018;68:361-371).

PMID- 29222912
TI  - Bringing the (disabled) body to personality psychology: A case study of Samantha.
AB  - OBJECTIVE: Personality psychology has largely ignored the experiences of people
      with disabilities. This article strives to bring the thriving, interdisciplinary
      field of disability studies to personality psychology via a case study of
      Samantha (N = 1). Samantha feels that she grew up as a hearing person who could
      not hear and is now a deaf person who can hear. METHOD: Narrative identity
      provides the theoretical, methodological, and analytical framework for the rich,
      qualitative examination of Samantha's life story, interwoven with approaches from
      disability studies and intersectionality theory. Two Life Story Interviews
      (McAdams, 2008), conducted 2 weeks prior to Samantha's cochlear implant surgery
      and again 7 weeks after the surgery, provide the foundation for this case study
      and are interpreted alongside additional self-report measures. Grounded theory
      methods were used to interpret Samantha's narrative identity. RESULTS: Samantha's
      story demonstrates the ways in which narrative identity can serve as a foundation
      for meaning and psychological well-being, as well as a demonstration of the ways
      in which the study of identity can be enriched by perspectives from disability
      studies. CONCLUSIONS: As an initial effort at integrating personality psychology
      and disability studies, this article sought to approach this task by privileging
      ethical representation over generalizability.

PMID- 29222913
TI  - Nonalcoholic fatty liver disease, metabolic syndrome, and the fight that will
      define clinical practice for a generation of hepatologists.

PMID- 29222914
TI  - Fibrolamellar carcinoma in the Carney complex: PRKAR1A loss instead of the
      classic DNAJB1-PRKACA fusion.
AB  - : Fibrolamellar carcinomas are characterized by activation of protein kinase A, a
      kinase composed of catalytic and regulatory subunits. PRKACA encodes a catalytic
      subunit of protein kinase A, and almost all fibrolamellar carcinomas have a
      heterozygous 400-kb deletion that leads to the fusion of DNAJB1 and PRKACA. The
      resulting DNAJB1-PRKACA fusion transcript is believed to activate protein kinase
      A by dysregulation of the catalytic portion of the protein. In contrast, PRKAR1A
      encodes one of the regulatory subunits of protein kinase A. We hypothesized that
      loss of function of this regulatory unit could also lead to protein kinase A
      activation and thus to fibrolamellar carcinoma. Because PRKAR1A mutations
      underlie the Carney complex, we searched for liver tumors in individuals with the
      Carney complex. We identified 3 individuals with fibrolamellar carcinomas and a
      personal history of the Carney complex. All three tumors displayed the typical
      morphology of fibrolamellar carcinoma and were positive for arginase, cytokeratin
      7, and cluster of differentiation 68. Fluorescence in situ hybridization was
      negative for PRKACA rearrangements. However, PRKAR1A sequencing identified
      pathogenic mutations in two of two cases with successful sequencing. In addition,
      all three cases were negative for PRKAR1A protein expression, consistent with
      inactivation of this key regulatory unit of protein kinase A. We also identified
      one additional fibrolamellar carcinoma in an individual without a documented
      history of the Carney complex who was negative for PRKACA rearrangements but had
      loss of PRKAR1A protein expression as well as PRKAR1A mutations. CONCLUSION:
      Fibrolamellar carcinoma can be part of the Carney complex; in this setting,
      fibrolamellar carcinomas have inactivating PRKAR1A mutations instead of the
      DNAJB1-PRKACA fusion gene found in sporadic fibrolamellar carcinomas, providing
      an alternate means for activation of protein kinase A. (Hepatology 2017).

PMID- 29222915
TI  - Ectopic expansion of engineered human liver tissue seeds using mature cell
      populations.

PMID- 29222917
TI  - Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic
      steatohepatitis, and associated fibrosis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated
      steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis.
      The majority of NAFLD subjects do not have NASH and do not carry a significant
      risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the
      prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low
      prevalence rates is noted from urban to rural areas. Given the prevalence of
      NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial.
      With increasing recognition of NASH as an important liver disease, the diagnosis
      of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy
      is the most accurate modality to diagnose and stage the severity of NASH, this
      method suffers from being invasive, costly, associated with potential
      complications, and plagued with interobserver variability of individual
      pathological features. A number of noninvasive modalities to diagnose NASH and
      stage liver fibrosis are being developed. These modalities include predictive
      models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver
      fibrosis (ELF). Other tests are based on radiological techniques, such as
      transient elastography (TE) or magnetic resonance elastography (MRE), which are
      used to estimate liver stiffness as a potential surrogate of hepatic fibrosis.
      Although a dynamic field of research, most of these diagnostic modalities have
      area under the curve ranging between 0.76 and 0.90%, with MRE having the best
      predictive performance. In summary, developing safe and easily accessible
      noninvasive modalities to accurately diagnose and monitor NASH and associated
      fibrosis is of utmost importance in clinical practice and clinical research.
      These tests are not only important to risk stratify subjects at the greatest risk
      for progressive liver disease, but also to serve as appropriate surrogate
      endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

PMID- 29222916
TI  - Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative
      patients with preemptive antiviral treatment: A modeling study.
AB  - : Under current guidelines, hepatitis C virus (HCV)-positive livers are not
      transplanted into HCV-negative recipients because of adverse posttransplant
      outcomes associated with allograft HCV infection. However, HCV can now be cured
      post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90%
      success; therefore, HCV-negative patients on the LT waiting list may benefit from
      accepting HCV-positive organs with preemptive treatment. Our objective was to
      evaluate whether and in which HCV-negative patients the potential benefit of
      accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated
      with HCV allograft infection. We developed a Markov-based mathematical model that
      simulated a virtual trial of HCV-negative patients on the LT waiting list to
      compare long-term outcomes in patients: (1) willing to accept any (HCV-negative
      or HCV-positive) liver versus (2) those willing to accept only HCV-negative
      livers. Patients receiving HCV-positive livers were treated preemptively with 12
      weeks of DAA therapy and had a higher risk of graft failure than those receiving
      HCV-negative livers. The model incorporated data from published studies and the
      United Network for Organ Sharing (UNOS). We found that accepting any liver
      regardless of HCV status versus accepting only HCV-negative livers resulted in an
      increase in life expectancy when Model for End-Stage Liver Disease (MELD) was
      >=20, and the benefit was highest at MELD 28 (0.172 additional life-years). The
      magnitude of clinical benefit was greater in UNOS regions with higher HCV
      positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity
      analysis demonstrated that model outcomes were robust. CONCLUSION: Transplanting
      HCV-positive livers into HCV-negative patients with preemptive DAA therapy could
      improve patient survival on the LT waiting list. Our analysis can help inform
      clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).

PMID- 29222918
TI  - Large-scale screening and characterisation of Lemna aequinoctialis and Spirodela
      polyrhiza strains for starch production.
AB  - Duckweed is considered a promising feedstock for bioethanol production due to its
      high biomass and starch production. Selection of duckweed strains with high
      starch accumulation is essential for application of duckweeds to bioethanol
      production. Geographic differentiation had a large influence on genetic diversity
      of duckweeds. Biomass production, starch content and starch amount in
      geographically isolated strains of 20 Lemna aequinoctialis and Spirodela
      polyrhiza were calculated to evaluate their potential for bioethanol production.
      The influence of different collection time, culture medium and NaCl concentration
      on starch accumulation of the best strains were analysed. The results showed that
      biomass production, starch content and starch production of duckweeds
      demonstrated clonal dependency. The best strain was L. aequinoctialis 6000, with
      biomass production of 15.38 +/- 1.47 g m-2 , starch content of 28.68 +/- 1.10%
      and starch production of 4.39 +/- 0.25 g m-2 . Furthermore, starch content of L.
      aequinoctialis 6000 was highest after 8 h of light, tap water was the best medium
      for starch induction, and NaCl did not induce starch accumulation. This study
      suggests duckweed biomass production and starch production demonstrate clonal
      dependency, indicating that extensive clonal comparisons will be required to
      identify the most suitable isolates for duckweed selective breeding for
      bioethanol.

PMID- 29222919
TI  - Pyroptosis, A novel player for alcoholic hepatitis?

PMID- 29222920
TI  - Starch-metal complexes and metal compounds.
AB  - Recently, metal derivatives of starch evoked considerable interest. Such metal
      derivatives can take a form of starch compounds bearing metal atoms and metal
      carrying moieties either covalently bound or complexed. Starch metal complexes
      may have a character of either Werner, inclusion, sorption or capillary
      complexes. In this publication, preparation, structure, properties and numerous
      current and potential applications of those compounds as well as benefits
      resulting from the application and formation of the complexes are presented. (c)
      2017 Society of Chemical Industry.

PMID- 29222921
TI  - Optimizing RNA-seq studies to investigate herbicide resistance.
AB  - Transcriptomic profiling, specifically via RNA sequencing (RNA-seq), is becoming
      one of the more commonly used methods for investigating non-target site
      resistance (NTSR) to herbicides due to its high throughput capabilities and
      utility in organisms with little to no previous sequence information. A review of
      the weed science RNA-seq literature revealed some basic principles behind
      generating quality data from these types of studies. First, studies that included
      more replicates per biotype and took steps to control for genetic background had
      significantly better control of false positives and, consequently, shorter lists
      of potential resistance genes to sift through. Pooling of biological replicates
      prior to sequencing was successful in some cases, but likely contributed to an
      overall increase in the false discovery rate. Although the inclusion of herbicide
      treated samples was common across most of the studies, it ultimately introduced
      difficulties in interpretation of the final results due to challenges in
      capturing the right sampling window after treatment and to the induction of
      stress responses in the injured herbicide-sensitive plants. RNA-seq is an
      effective tool for NTSR gene discovery, but careful consideration should be given
      to finding the most powerful and cost-effective balance between replicate number,
      sequencing depth and treatment number. (c) 2017 Society of Chemical Industry.

PMID- 29222922
TI  - Survival of children after liver transplantation for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is
      often associated with inherited liver disease. It is, however, unclear whether
      liver transplantation (LT) for HCC in childhood with or without associated
      inherited disease has a comparable outcome to adult HCC. On the basis of data
      from the European Liver Transplant Registry (ELTR), we aimed to investigate if
      there are differences in patient and graft survival after LT for HCC between
      children and adults and between patients with underlying inherited versus
      noninherited liver disease, respectively. We included all 175 children who
      underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these,
      38 had an associated inherited liver disease. Adult HCC patients with (n = 79)
      and without (n = 316, matched by age, sex, and LT date) inherited liver disease
      served as an adult comparison population. We used multivariable piecewise Cox
      regression models with shared frailty terms (for LT center) to compare patient
      and graft survival between the different HCC groups. Survival analyses
      demonstrated a superior longterm survival of children with inherited liver
      disease when compared with children with HCC without inherited liver disease
      (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with
      inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no
      survival difference between adults with and without inherited disease (HR, 1.05;
      95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of
      children with an HCC based on inherited disease should be acknowledged when
      considering transplantation and prioritization for these patients. Further
      prospective studies accounting for tumor size and extension at LT are necessary
      to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.

PMID- 29222923
TI  - Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking
      in Alcohol-Preferring (P) Rats.
AB  - BACKGROUND: This study examined whether combining naltrexone (NTX) with bupropion
      (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P)
      rats with a genetic predisposition toward high voluntary alcohol intake than
      either drug alone. METHODS: Alcohol-experienced, adult, male, P rats were fed NTX
      alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone
      in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle
      (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5
      consecutive days. RESULTS: When administered alone, neither NTX (10.0 mg/kg BW)
      nor BUP, in either of 2 doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary
      alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0
      mg/kg BUP) and given as a single medication significantly reduced alcohol
      consumption throughout prolonged treatment. CONCLUSIONS: Combining low doses of
      NTX and BUP, each of which is ineffective when given alone, increases the
      efficacy of the medication. Low drug doses circumvent the problem of negative
      side effects that can occur with higher doses of either drug. A reduction in side
      effects can facilitate patient compliance and improve clinical outcomes for
      alcoholics and heavy drinkers who want to reduce their alcohol intake. The
      results, together with those from our prior studies, demonstrate the strength of
      a combinatorial pharmacotherapeutic approach to the treatment of alcohol use
      disorder.

PMID- 29222924
TI  - Evolving role of obeticholic acid in primary biliary cholangitis.

PMID- 29222925
TI  - Quantification of photonic localization properties of targeted nuclear mass
      density variations: Application in cancer-stage detection.
AB  - Light localization is a phenomenon which arises due to the interference effects
      of light waves inside a disordered optical medium. Quantification of degree light
      localization in optical media is widely used for characterizing degree of
      structural disorder in that media. Recently, this light localization approach was
      extended to analyze structural changes in biological cell like heterogeneous
      optical media, with potential application in cancer diagnostics. Confocal
      fluorescence microscopy was used to construct "optical lattices," which
      represents 2-dimensional refractive index map corresponding to the spatial mass
      density distribution of a selected molecule inside the cell. The structural
      disorder properties of the selected molecules were evaluated numerically using
      light localization strength in these optical lattices, in a single parameter
      called "disorder strength." The method showed a promising potential in
      differentiating cancerous and non-cancerous cells. In this paper, we show that by
      quantifying submicron scale disorder strength in the nuclear DNA mass density
      distribution, a wide range of control and cancerous breast and prostate cells at
      different hierarchy levels of tumorigenicity were correctly distinguished. We
      also discuss how this photonic technique can be used in examining tumorigenicity
      level in unknown prostate cancer cells, and potential to generalize the method to
      other cancer cells.

PMID- 29222926
TI  - Depressive personality vulnerability in chronic physical pain: Centrality of
      sociotropy.
AB  - OBJECTIVE: Chronic physical pain is one of modern medicine's principal
      challenges. Recently, there has been a keen research interest in the role of
      depressive personality vulnerability (DPV) in the course of chronic pain. This is
      the first attempt to examine the role of three leading DPV dimensions-sociotropy,
      autonomy, and self-criticism-in chronic pain. METHOD: Chronic pain patients (N =
      428) were assessed four times as to their pain, disability, anxious depression,
      and pain-based catastrophizing. At Time 1, sociotropy, autonomy, and self
      criticism were also assessed. The effects of sociotropy, autonomy, and self
      criticism on pain, disability, anxious depression, and pain-based catastrophizing
      were examined using structural equation modeling analyses. RESULTS: All DPV
      dimensions uniquely predicted Time 1, but not Time 2, anxious depression.
      Sociotropy predicted Time 1 pain and catastrophizing over and above anxious
      depression, as well as an increase in catastrophizing over time. Autonomy
      predicted a decrease in catastrophizing and disability, and Time 1 anxious
      depression predicted an increase in self-criticism. CONCLUSIONS: Sociotropy
      appears to be a unique dimension of DPV in chronic pain.

PMID- 29222928
TI  - The role of the kidney in combined liver-kidney transplantation.

PMID- 29222927
TI  - Diaheliotropic leaf movement enhances leaf photosynthetic capacity and
      photosynthetic light and nitrogen use efficiency via optimising nitrogen
      partitioning among photosynthetic components in cotton (Gossypium hirsutum L.).
AB  - Phototropic leaf movement of plants is an effective mechanism for adapting to
      light conditions. Light is the major driver of plant photosynthesis. Leaf N is
      also an important limiting factor on leaf photosynthetic potential. Cotton
      (Gossypium hirsutum L.) exhibits diaheliotropic leaf movement. Here, we compared
      the long-term photosynthetic acclimation of fixed leaves (restrained) and free
      leaves (allowed free movement) in cotton. The fixed leaves and free leaves were
      used for determination of PAR, leaf chlorophyll concentration, leaf N content and
      leaf gas exchange. The measurements were conducted under clear sky conditions at
      0, 7, 15 and 30 days after treatment (DAT). The results showed that leaf N
      allocation and partitioning among different components of the photosynthetic
      apparatus were significantly affected by diaheliotropic leaf movement.
      Diaheliotropic leaf movement significantly increased light interception per unit
      leaf area, which in turn affected leaf mass per area (LMA), leaf N content (NA )
      and leaf N allocation to photosynthesis (NP ). In addition, cotton leaves
      optimised leaf N allocation to the photosynthetic apparatus by adjusting leaf
      mass per area and NA in response to optimal light interception. In the presence
      of diaheliotropic leaf movement, cotton leaves optimised their structural tissue
      and photosynthetic characteristics, such as LMA, NA and leaf N allocation to
      photosynthesis, so that leaf photosynthetic capacity was maximised to improve the
      photosynthetic use efficiency of light and N under high light conditions.

PMID- 29222929
TI  - HIV+ deceased donor referrals: A national survey of organ procurement
      organizations.
AB  - BACKGROUND: HIV-infected (HIV+) donor organs can be transplanted into HIV+
      recipients under the HIV Organ Policy Equity (HOPE) Act. Quantifying HIV+ donor
      referrals received by organ procurement organizations (OPOs) is critical for HOPE
      Act implementation. METHODS: We surveyed the 58 USA OPOs regarding HIV+ referral
      records and newly discovered HIV+ donors. Using data from OPOs that provided
      exact records and CDC HIV prevalence data, we projected a national estimate of
      HIV+ referrals. RESULTS: Fifty-five (95%) OPOs reported HIV+ referrals ranging
      from 0 to 276 and newly discovered HIV+ cases ranging from 0 to 10 annually. Six
      OPOs in areas of high HIV prevalence reported more than 100 HIV+ donor referrals.
      Twenty-seven (47%) OPOs provided exact HIV+ referral records and 28 (51%) OPOs
      provided exact records of discovered HIV+ cases, totaling 1450 HIV+ referrals and
      39 discovered HIV+ donors in the prior year. These OPOs represented 67% and 59%
      of prevalent HIV cases in the USA; thus, we estimated 2164 HIV+ referrals and 66
      discovered HIV+ cases nationally per year. CONCLUSIONS: OPOs reported a high
      volume of HIV+ referrals annually, of which a subset will be medically eligible
      for donation. Particularly in areas of high HIV prevalence, OPOs require ongoing
      support to implement the HOPE Act.

PMID- 29222930
TI  - Regression of HCV cirrhosis: Time will tell.

PMID- 29222931
TI  - The challenge of herbicide resistance around the world: a current summary.
AB  - Herbicide-resistant weeds have been observed since the early years of synthetic
      herbicide development in the 1950s and 1960s. Since that time there has been a
      consistent increase in the number of cases of herbicide resistance and the impact
      of herbicide-resistant weeds. Although the nature of crop production varies
      widely around the world, herbicides have become a primary tool for weed control
      in most areas. Dependence on herbicides continues to increase as global
      populations migrate away from rural areas to cities and the agricultural labor
      force declines. This increased use of herbicides and the concurrent selection
      pressure have resulted in a rise in cases of multiple resistance, leaving some
      farmers with few or no herbicide options for certain weed infestations. Global
      population and economic forces drive many farmer choices regarding crop
      production and weed control. The challenge is how to insert best management
      practices into the decision-making process while addressing various economic and
      regulatory needs. This review endeavors to provide a current overview of
      herbicide resistance challenges in the major crop production areas of the world
      and discusses some research initiatives designed to address portions of the
      problem. (c) 2017 Society of Chemical Industry.

PMID- 29222932
TI  - A-Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin-Induced
      Neuropathy.
AB  - Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the
      pathophysiological and molecular mechanisms as well as the contribution of
      different primary afferent fiber systems are unclear. Therefore, patients with
      oxaliplatin-induced acute neuropathy with (n = 6) and without (n = 7) cold
      hyperalgesia were tested by applying a preferential blockade of peripheral
      myelinated A-fiber afferents in combination with quantitative sensory testing.
      Additionally, an interview-based questionnaire assessed the severity of symptoms
      and the impact on daily activities. Results indicate a deficit of cold perception
      in patients without cold hyperalgesia compared to patients with cold hyperalgesia
      prior to A-fiber blockade. In patients with cold hyperalgesia, a preferential
      blockade of A-fibers abolished cold hyperalgesia. This suggests that oxaliplatin
      induced cold hyperalgesia is mediated by A-fibers and that a deficit in A-fiber
      function might prevent the development of cold hyperalgesia. The work supports
      findings in rodents and in human sural nerve biopsies indicating that oxaliplatin
      interferes with axonal ion conductance in intact A-fibers by sensitizing
      potassium and/or sodium channels. Drugs that act on these molecular targets might
      be of potential value to treat oxaliplatin-induced cold hyperalgesia.

PMID- 29222933
TI  - Benefits of emotional integration and costs of emotional distancing.
AB  - OBJECTIVE: Three studies explored the consequences of the self-determination
      theory conception of integrative emotion regulation (IER; Ryan & Deci, 2017),
      which involves an interested stance toward emotions. Emotional, physiological,
      and cognitive consequences of IER were compared to the consequences of emotional
      distancing (ED), in relation to a fear-eliciting film. METHOD: In Study 1, we
      manipulated emotion regulation by prompting students' (N = 90) IER and ED and
      also included a control group. Then we tested groups' defensive versus
      nondefensive emotional processing, coded from post-film written texts. Study 2 (N
      = 90) and Study 3 (N = 135) used the same emotion regulation manipulations but
      exposed participants to the fear-eliciting film twice, 72 hr apart, to examine
      each style's protection from adverse emotional, physiological, and cognitive
      costs at second exposure. RESULTS: Participants who had been prompted to practice
      IER were expected to benefit more than participants in the ED and control groups
      at second exposure, as manifested in lower arousal and better cognitive capacity.
      Overall, results supported our hypotheses. CONCLUSIONS: The current studies
      provide some support for the assumption that in comparison to ED, taking interest
      in and accepting one's negative emotions are linked with less defensive
      processing of negative experiences and with better functioning.

PMID- 29222934
TI  - Design of a secure remote management module for a software-operated medical
      device.
AB  - Software-based medical devices need to be maintained throughout their entire life
      cycle. The efficiency of after-sales maintenance can be improved by managing
      medical systems remotely. This paper presents how to design the remote access
      function extensions in order to prevent risks imposed by uncontrolled remote
      access. A thorough analysis of standards and legislation requirements regarding
      safe operation and risk management of medical devices is presented. Based on the
      formal requirements, a multi-layer machine design solution is proposed that
      eliminates remote connectivity risks by strict separation of regular device
      functionalities from remote management service, deploys encrypted communication
      links and uses digital signatures to prevent mishandling of software images. The
      proposed system may also be used as an efficient version update of the existing
      medical device designs.

PMID- 29222935
TI  - Risk factors for positive resection margins of breast cancer tumorectomy specimen
      following breast-conserving surgery.
AB  - Background The aim of the study was to identify risk factors for positive
      surgical margins in breast-conserving surgery for breast cancer and to evaluate
      the influence of surgical experience in obtaining complete resection. Methods All
      lumpectomies for invasive breast carcinoma and ductal carcinoma in situ (DCIS)
      between April 2008 and March 2010 were selected from the database of a single
      institution. Re-excision rates for positive margins as well as patient and
      histopathologic tumor characteristics were analyzed. Surgical experience was
      staged by pairs made of Resident plus Specialist or Consultant. Two periods were
      defined. During period A, the majority of operations were performed by Residents
      under supervision of Specialist or Consultant. During period B, only palpable
      tumors were operated by Residents. Results The global re-excision rate was 27%
      (50 of 183 patients). The presence of DCIS increased the risk for positive
      margins: 60% (nine of 15 patients) in the case of sole DCIS compared to 26% (41
      of 160 patients) for invasive cancer (p = 0.005) and 35% (42 of 120 patients) in
      the case of peritumoral DCIS compared to 11% (seven of 62 patients) in the case
      of sole invasive cancer (p = 0.001). Re-excision rate decreased from 36% (23 of
      64 patients) during period A to 23% (27 of 119 patients) during period B (p =
      0.055). There was no significant difference between the surgical pairs.
      Conclusion In our study, DCIS was the only risk factor for positive surgical
      margins. Breast-conserving surgery for non-palpable tumors should be performed by
      Specialists, however, palpable tumors can be safely operated by Residents under
      supervision.

PMID- 29222936
TI  - Role of central oxytocin and dopamine systems in nociception and their possible
      interactions: suggested hypotheses.
AB  - Central oxytocin and dopamine have an important role in the process of
      nociception at the spinal level as well as supraspinal structures, e.g. anterior
      cingulate cortex, insular cortex, amygdala, nucleus accumbens, and hypothalamus.
      Many studies have pointed out the importance of both systems in the pain
      descending modulatory system and in pain-related symptoms in some chronic
      disorders, e.g. Parkinson disease and fibromyalgia. The interaction between
      oxytocin and dopamine systems has been addressed in some motivational behaviors,
      e.g. maternal and sexual behaviors, pair bonding, and salience. In this aspect,
      we propose that an oxytocin-dopamine interaction could be present in nociception,
      and we also explain the possible hypotheses of such an interaction between these
      systems.

PMID- 29222937
TI  - Preoperative T1 Slope as a Predictor of Change in Cervical Alignment and Range of
      Motion After Cervical Disc Arthroplasty.
AB  - BACKGROUND This study analyzed the effect of preoperative T1 slope on cervical
      alignment and range of motion (ROM) after cervical disc arthroplasty (CDA) in
      patients with cervical degenerative disease. MATERIAL AND METHODS This
      retrospective study included 32 patients with single-level symptomatic cervical
      disc disease who underwent CDA with the Mobi-C cervical disc prosthesis and had a
      mean follow-up of 26.8+/-6.4 months. Standing lateral, flexion, and extension X
      rays of the cervical spine were obtained preoperatively and postoperatively at 24
      month follow-up. Simple linear regression analysis was used to assess the impact
      of preoperative T1 slope on changes from preoperative values in radiologic
      parameters. RESULTS Compared to preoperative values, at 24-month follow-up, there
      was a significant increase in mean functional spinal unit (FSU) angle (+7.4
      degrees ), upper adjacent segment (UAS) angle (+3.1 degrees ), and overall
      cervical alignment (C2-C7 angle) (+6.3 degrees ), and a significant decrease in
      mean lower adjacent segment (LAS) angle (-2.4 degrees ). Mean ROM of the FSU (
      3.6 degrees ), LAS (-3.0 degrees ), and overall cervical spine (-11.5 degrees )
      significantly decreased, and mean ROM of the UAS (+1.6 degrees ) significantly
      increased. There were significant correlations between preoperative T1 slope and
      mean change from preoperative value in FSU angle, C2-C7 angle, and ROM of the
      overall cervical spine (C2-C7). CONCLUSIONS T1 slope is useful for evaluating
      changes in the FSU angle, C2-C7 angle, and ROM of the overall cervical spine
      following CDA with the Mobi-C disc. Patients with a large preoperative T1 slope
      may be good candidates for CDA with the Mobi-C prosthesis due its motion
      maintenance and the fact that it has little adverse impact on sagittal alignment.
      It also could be a good option in terms of sagittal alignment improvement or
      motion maintenance for patients with kyphosis.

PMID- 29222939
TI  - Which outcomes are reported in cellulitis trials? Results of a review of outcomes
      included in cellulitis trials and a patient priority setting survey.
AB  - BACKGROUND: There is an emerging need to develop consistent outcomes in clinical
      trials to allow effective comparison of treatment effects. No systematic review
      has previously looked at the reporting of outcome measures used in randomized
      controlled trials (RCTs) on the treatment and prevention of cellulitis
      (erysipelas). OBJECTIVES: The primary aim of this review was to describe the
      breadth of outcomes reported from RCTs on cellulitis treatment and prevention.
      The secondary aim was to identify outcome themes from patients' and healthcare
      professionals' feedback from a cellulitis Priority Setting Partnership (PSP).
      METHODS: We conducted a review of all outcome measures used in RCTs from two
      recent Cochrane reviews. Free-text responses from a cellulitis priority setting
      survey were used to understand the perspectives of patients and healthcare
      professionals. RESULTS: Outcomes from 42 RCTs on treatment of cellulitis and six
      RCTs on prevention of cellulitis were reviewed. Only 28 trials stated their
      primary outcome. For trials assessing treatment of cellulitis, clinical response
      to treatment was categorized in 25 different ways. Five of these trials used an
      outcome that was in accordance with FDA guidance and only four trials
      incorporated either quality of life or patient satisfaction. For trials assessing
      prevention of cellulitis, recurrence was the key outcome measure. From the
      cellulitis PSP, prevention of recurrence, clinical features and long-term disease
      impact were the most important outcome themes for patients. CONCLUSIONS: We have
      shown that in cellulitis treatment and prevention research, there is significant
      heterogeneity in clinical outcomes, inadequate focus on patient-reported
      outcomes, and a disparity between what is currently measured and what patients
      and healthcare professionals feel is important. We recommend that future
      cellulitis treatment trials consider the use of longer-term outcomes to capture
      recurrence and long-term morbidity, as well as short-term resolution of acute
      infection.

PMID- 29222938
TI  - Role of angiogenic factors in the pathogenesis and management of pre-eclampsia.
AB  - The cause of pre-eclampsia is unknown. Different postulates have been developed
      to explain its pathogenesis. The two-stage theory and angiogenic imbalance are
      two notable postulates of the disease. Together, they propose that there is a
      lack of cytotrophoblastic invasion of the uterine spiral arteries in pre
      eclampsia. The lumen of these arteries remains narrow instead of converting to
      the wide channels seen in normal pregnancy, and result in poor placental
      perfusion. Coupled with maternal susceptibility, this process leads to the
      release of mediators, including an excess of anti-angiogenic factors that result
      in the clinical manifestations of the disease. Circulating levels of anti
      angiogenic factors such as soluble fms-like tyrosine kinase-1 increase, whereas
      pro-angiogenic factors such as placental growth factor decrease. Assessment of
      the circulating concentrations of these angiogenic factors, such as the soluble
      fms-like tyrosine kinase-1/placental growth factor ratio, has diverse clinical
      relevance in pre-eclampsia. The present review describes the role of angiogenic
      factors in the pathogenesis and management of pre-eclampsia.

PMID- 29222940
TI  - An open conformation of ADAMTS-13 is a hallmark of acute acquired thrombotic
      thrombocytopenic purpura.
AB  - : Essentials Conformational changes in ADAMTS-13 are part of its mode-of-action.
      The murine anti-ADAMTS-13 antibody 1C4 discriminates between folded and open
      ADAMTS-13. ADAMTS-13 conformation is open in acute acquired thrombotic
      thrombocytopenic purpura (TTP). Our study forms an important basis to fully
      elucidate the pathophysiology of TTP. SUMMARY: Background Acquired thrombotic
      thrombocytopenic purpura (aTTP) is an autoimmune disorder characterized by absent
      ADAMTS-13 activity and the presence of anti-ADAMTS-13 autoantibodies. Recently,
      it was shown that ADAMTS-13 adopts a folded or an open conformation. Objectives
      As conformational changes in self-antigens play a role in the pathophysiology of
      different autoimmune diseases, we hypothesized that the conformation of ADAMTS-13
      changes during acute aTTP. Methods Antibodies recognizing cryptic epitopes in the
      spacer domain were generated. Next, the conformation of ADAMTS-13 in 40 healthy
      donors (HDs), 99 aTTP patients (63 in the acute phase versus 36 in remission), 12
      hemolytic-uremic syndrome (HUS) patients and 63 sepsis patients was determined
      with ELISA. Results The antibody 1C4 recognizes a cryptic epitope in ADAMTS-13.
      Therefore, we were able to discriminate between a folded and an open ADAMTS-13
      conformation. We showed that ADAMTS-13 in HDs does not bind to 1C4, indicating
      that ADAMTS-13 circulates in a folded conformation. Similar results were obtained
      for HUS and sepsis patients. In contrast, ADAMTS-13 of acute aTTP patients bound
      to 1C4 in 92% of the cases, whereas, in most cases, this binding was abolished
      during remission, showing that the conformation of ADAMTS-13 is open during an
      acute aTTP episode. Conclusions Our study shows that, besides absent ADAMTS-13
      activity and the presence of anti-ADAMTS-13 autoantibodies, an open ADAMTS-13
      conformation is also a hallmark of acute aTTP. Demonstrating this altered ADAMTS
      13 conformation in acute aTTP will help to further unravel the pathophysiology of
      aTTP and lead to improved therapy and diagnosis.

PMID- 29222941
TI  - Characterization of the spoilage potential of pure and mixed cultures of
      bacterial species isolated from tropical yellowfin tuna (Thunnus albacares).
AB  - AIM: The spoilage potential of 28 bacterial strains isolated from spoiled raw
      yellowfin tuna was evaluated. METHODS AND RESULTS: Bacterial species were
      inoculated in irradiated tuna matrix. Chemical changes, bacterial growth and
      sensory quality were monitored during aerobic storage at 8 degrees C. Pseudomonas
      spp., Enterobacter spp. and Escherichia hermanii had no spoiling effect.
      Brochothrix thermosphacta and Carnobacterium divergens/maltaromaticum developed
      moderate unpleasant odours. Hafnia paralvei and Serratia spp. released strong off
      odours (pyrrolidine, sulphur/cabbage). No bacterial group (except H. paralvei)
      combined with Pseudomonas spp. deteriorated the sensory quality of tuna. When C.
      divergens/maltaromaticum was associated with H. paralvei or B. thermosphacta, the
      odour is close to the naturally contaminated tuna stored on the same conditions.
      The pH, total volatile basic nitrogen (TVBN) and trimethylamine (TMA) were not
      correlated with the spoilage. CONCLUSIONS: The bacterial species had a different
      impact on the sensory quality of the fish. The bacterial interactions lead to an
      enhancement or an inhibition of the spoilage potential and the bacterial growth.
      SIGNIFICANCE AND IMPACT OF STUDY: The specific spoilage organism (SSO) appears to
      be an association of lactic acid bacteria (LAB) with Enterobacteriaceae or B.
      thermosphacta. Pseudomonas, often dominant at the sensory rejection time, is not
      a good quality indicator.

PMID- 29222943
TI  - Ascariasis seen by videocapsule endoscopy.

PMID- 29222942
TI  - Microbial communities in natural rubber coagula during maturation: impacts on
      technological properties of dry natural rubber.
AB  - AIM: To characterize microbial communities present in natural rubber (NR) coagula
      from Hevea brasiliensis latex during maturation and identify microbial taxa
      (bacteria and fungi) having an impact on dry NR properties. METHODS AND RESULTS:
      Microbial community dynamics in NR coagula maturated under controlled conditions
      were compared and related with the evolution of dry NR properties. The
      pyrosequencing of 16S (119 837 effective reads) and 18S (131 879 effective reads)
      rRNA gene regions was performed on 21 samples covering different maturation times
      and two aeration conditions. Results showed a relatively high bacterial richness
      (Chao1 estimates of 200-1000) associated with significant bacterial dynamics.
      Lactic acid bacteria (LAB) were dominant in the first days of maturation. Then,
      in aerobic conditions, development of Actinobacteria represented by the family
      Microbacteriaceae was associated with alkalinization of the samples and a higher
      sensitivity of NR to thermo-oxidation as evaluated by its plasticity retention
      index (PRI). In anaerobiosis, the reduced development of bacteria, mostly LAB
      present, was associated with improved NR properties (higher initial plasticity P0
      and PRI). CONCLUSIONS: The involvement of micro-organisms in the evolution of dry
      NR properties during the maturation of NR coagula was confirmed. The importance
      of the structure and dynamics of microbial communities is specifically
      highlighted. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural rubber is a key
      elastomer for the tyre industry and for a variety of other applications. The
      majority of raw NR is obtained by natural coagulation of H. brasiliensis latex
      under the activity of micro-organisms. An improved understanding of the microbial
      communities involved in the maturation of NR coagula may lead to an improvement
      in the production process of raw NR to provide a better consistency in NR
      quality.

PMID- 29222944
TI  - Cerebral microbleeds: a magnetic resonance imaging review of common and less
      common causes.
AB  - Cerebral microbleeds (CMBs) are small foci of (acute, subacute or chronic) blood
      products, best seen using magnetic resonance imaging (MRI) techniques sensitive
      to iron deposits (i.e. gradient-echo T2*-weighted and susceptibility-weighted
      imaging), frequently encountered in small vessel disease (SVD) (with hypertensive
      vasculopathy and cerebral amyloid angiopathy as the most frequent conditions) and
      also in other disorders. In this review, the MRI characteristics of CMBs and the
      associated MRI abnormalities encountered in common and less common SVD and non
      SVD conditions are the main focus. Identification of the origin of CMBs depends
      on their localization, the presence of other associated MRI abnormalities, and
      the patient's history and clinical state.

PMID- 29222945
TI  - Children with atopic dermatitis may have unacknowledged contact allergies
      contributing to their skin symptoms.
AB  - BACKGROUND: Whether children with atopic dermatitis have an altered risk of
      contact allergy than children without atopic dermatitis is frequently debated and
      studies have been conflicting. Theoretically, the impaired skin barrier in atopic
      dermatitis (AD) facilitates the penetration of potential allergens and several
      authors have highlighted the risk of underestimating and overlooking contact
      allergy in children with atopic dermatitis. OBJECTIVE: To determine the
      prevalence of contact allergy in Danish children with atopic dermatitis and
      explore the problem of unacknowledged allergies maintaining or aggravating the
      skin symptoms. METHODS: In a cross-sectional study, 100 children and adolescents
      aged 5-17 years with a diagnosis of atopic dermatitis were patch tested with a
      paediatric series of 31 allergens. RESULTS: Thirty per cent of the children had
      at least one positive patch test reaction, and 17% had at least one contact
      allergy that was relevant to the current skin symptoms. The risk of contact
      allergy was significantly correlated to the severity of atopic dermatitis. Metals
      and components of topical skincare products were the most frequent sensitizers.
      CONCLUSION: Patch testing is relevant as a screening tool in the management of
      children with atopic dermatitis as they may have unacknowledged contact allergies
      contributing to or maintaining their skin symptoms. Children with atopic
      dermatitis seem to be at greater risk of sensitization to certain allergens
      including metals and components of skincare products.

PMID- 29222946
TI  - Triheptanoin protects against status epilepticus-induced hippocampal
      mitochondrial dysfunctions, oxidative stress and neuronal degeneration.
AB  - Triheptanoin, the triglyceride of heptanoate, is anaplerotic (refills deficient
      tricarboxylic acid cycle intermediates) via the propionyl-CoA carboxylase
      pathway. It has been shown to be neuroprotective and anticonvulsant in several
      models of neurological disorders. Here, we investigated the effects of
      triheptanoin against changes of hippocampal mitochondrial functions, oxidative
      stress and cell death induced by pilocarpine-induced status epilepticus (SE) in
      mice. Ten days of triheptanoin pre-treatment did not protect against SE, but it
      preserved hippocampal mitochondrial functions including state 2, state 3 ADP,
      state 3 uncoupled respiration, respiration linked to ATP synthesis along with the
      activities of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase
      complex 24 h post-SE. Triheptanoin prevented the SE-induced reductions of
      hippocampal mitochondrial superoxide dismutase activity and plasma antioxidant
      status as well as lipid peroxidation. It also reduced neuronal degeneration in
      hippocampal CA1 and CA3 regions 3 days after SE. In addition, heptanoate
      significantly reduced hydrogen peroxide-induced cell death in cultured neurons.
      In situ hybridization localized the enzymes of the propionyl-CoA carboxylase
      pathway, specifically Pccalpha, Pccbeta and methylmalonyl-CoA mutase to adult
      mouse hippocampal pyramidal neurons and dentate granule cells, indicating that
      anaplerosis may occur in neurons. In conclusion, triheptanoin appears to have
      anaplerotic and antioxidant effects which contribute to its neuroprotective
      properties.

PMID- 29222947
TI  - Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe
      plaque psoriasis: a randomized, placebo-controlled, ascending-dose study.
AB  - BACKGROUND: The interleukin (IL)-23/IL-17 pathway is central in the pathogenesis
      of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23-specific
      monoclonal antibody, has been demonstrated in global phase III studies of plaque
      psoriasis. OBJECTIVES: To evaluate the safety, efficacy and pharmacokinetics of
      single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe
      plaque psoriasis. METHODS: Patients with >= 10% of total body surface area
      involvement and a Psoriasis Area and Severity Index (PASI) >= 12 were randomized
      (5 : 1) to receive guselkumab or placebo in four cohorts of this double-blind,
      placebo-controlled, single ascending-dose, single-centre study. Safety,
      pharmacokinetics and clinical response were monitored at baseline and specific
      time points over a 24-week follow-up period. RESULTS: To week 24, 55% (11/20) of
      patients in the guselkumab group and 50% (2/4) in the placebo group experienced
      >=1 adverse event (AE). No deaths, serious AEs or AEs leading to treatment
      discontinuation were reported. Maximum clinical response was seen at week 16 with
      PASI 75 (>= 75% improvement from baseline PASI) response in two of five (10 mg),
      four of five (30 mg and 300 mg) and three of five (100 mg) patients; and PASI 90
      (>= 90% improvement from baseline PASI) in zero of five (10 mg), three of five
      (30 mg), two of five (100 mg) and three of five (300 mg) patients. Mean maximum
      serum concentration (Cmax ) and area under the curve from time zero to infinity
      values increased in a dose-proportional manner with a mean terminal half-life of
      15.6-17.6 days and median time to reach Cmax of 4-6 days. CONCLUSIONS: Guselkumab
      was generally well-tolerated and exhibited sustained high levels of clinical
      response in Japanese patients with moderate-to-severe psoriasis.

PMID- 29222948
TI  - Force coordination strategies in on-water single sculling: Are asymmetries
      related to better rowing performance?
AB  - Asymmetries of the rowing stroke cycle have been assessed with reference to
      kinematics and foot-force measures in laboratory testing environments. It remains
      unclear how asymmetries in propulsive kinetic measures are related to on-water
      rowing performance. A new approach for the evaluation of both global and local
      asymmetries across the entire movement was used to assess the continuous role of
      asymmetries and whether these change according to the level of competitive
      representation. Twenty-seven highly skilled female rowers (national and
      international competition level), rowing at 32 strokes per minute in a single
      scull boat, were evaluated. A symmetry index (SI) and functional data analysis
      (FDA) techniques were applied to a continuous difference time-series, which
      described fluctuating asymmetry in propulsive pin forces for each rower.
      Univariate ANOVAs revealed that differences in asymmetries were present as a
      factor of competition level for the SI and results of FDA. International athletes
      were more likely to utilize an asymmetry strategy with increased stroke-side
      (port-side) force early in the drive phase and increased bow-side (starboard)
      force through the second half of the drive. This was likely the result of
      international performers customizing their movement strategies relative to known
      boat mechanical offsets. The first half of the drive phase was also found to be
      an adaptive part of the rowing stroke cycle, suggesting asymmetries may have a
      functional role in successful execution of movements during the rowing stroke.

PMID- 29222949
TI  - A switch from GABA inhibition to excitation of vasopressin neurons exacerbates
      the development angiotensin II-dependent hypertension.
AB  - Hypothalamic magnocellular neurons secrete vasopressin into the systemic
      circulation to maintain blood pressure by increasing renal water reabsorption and
      by vasoconstriction. When blood pressure rises, baroreflex activation normally
      inhibits vasopressin neurons via activation of GABAergic inputs. However, plasma
      vasopressin levels are paradoxically elevated in several models of hypertension
      and in some patients with essential hypertension, despite increased blood
      pressure. We have previously shown that vasopressin neuron activity is increased
      early in the development of moderate angiotensin II-dependent hypertension via
      blunted baroreflex inhibition of vasopressin neurons. Here, we show that
      antagonism of vasopressin-induced vasoconstriction slows the development of
      hypertension and that local administration of a GABAA receptor antagonist
      inhibits vasopressin neurons during, but not before, the onset of hypertension.
      Taken together, our data suggest that vasopressin exacerbates the increase in
      blood pressure evident early in the development hypertension and that blunted
      baroreflex inhibition of vasopressin neurons is underpinned by an excitatory
      shift in their response to endogenous GABA signalling. This article is protected
      by copyright. All rights reserved.

PMID- 29222950
TI  - Tolerance design of patient-specific range QA using the DMAIC framework in proton
      therapy.
AB  - PURPOSE: To implement the DMAIC (Define-Measure-Analyze-Improve-Control) can be
      used for customizing the patient-specific QA by designing site-specific range
      tolerances. METHODS: The DMAIC framework (process flow diagram, cause and effect,
      Pareto chart, control chart, and capability analysis) were utilized to determine
      the steps that need focus for improving the patient-specific QA. The patient
      specific range QA plans were selected according to seven treatment site groups, a
      total of 1437 cases. The process capability index, Cpm was used to guide the
      tolerance design of patient site-specific range. RESULTS: For prostate field, our
      results suggested that the patient range measurements were capable at the current
      tolerance level of +/-1 mm in clinical proton plans. For other site-specific
      ranges, we analyzed that the tolerance tends to be overdesigned to insufficient
      process capability calculated by the patient-specific QA data. The customized
      tolerances were calculated for treatment sites. Control charts were constructed
      to simulate the patient QA time before and after the new tolerances were
      implemented. It is found that the total simulation QA time was decreased on
      average of approximately 20% after establishing new site-specific range
      tolerances. We simulated the financial impact of this project. The QA failure for
      whole process in proton therapy would lead up to approximately 30% increase in
      total cost. CONCLUSION: DMAIC framework can be used to provide an effective QA by
      setting customized tolerances. When tolerance design is customized, the quality
      is reasonably balanced with time and cost demands.

PMID- 29222951
TI  - Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in
      pentylenetetrazole-induced epilepsy through the induction of Homer1a.
AB  - Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been
      implicated in epilepsy pathogenesis to prevent the neuronal circuits from
      hyperexcitability. Recent findings suggest a role for neuronal PAS domain protein
      4 (Npas4), an activity-dependent neuron-specific transcription factor in
      epileptogenesis, however, the underlying mechanism by which Npas4 regulates
      epilepsy remains unclear. We herein propose that limbic seizure activity up
      regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to
      epileptogenesis in mice. The expression level of Npas4mRNA was significantly
      increased after the pentylenetetrazol (PTZ) treatment. Npas4KO mice developed
      kindling more rapidly than their wild-type littermates. The expression of Homer1a
      in the hippocampus increased after seizure activity. Npas4 increased Homer1a
      promoter activity in COS7 cells. The PTZ-stimulated induction of Homer1a was
      attenuated in the hippocampus of Npas4KO mice. The combination of fluorescence in
      situ hybridization and immunohistochemical analyses revealed that Homer1amRNA co
      localized with the Npas4 protein after the convulsive seizure response. PTZ
      reduced excitatory synaptic transmission at the associational/commissural fibers
      CA3 synapses through the Npas4-mediated down-regulation of postsynaptic alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in hippocampal CA3
      neurons. The adeno-associated virus (AAV)-mediated expression of Homer1a resulted
      in lower alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate
      receptor GluA1 subunit levels in the hippocampal plasma membrane fraction than in
      that from AAV-EGFP-transfected Npas4KO mice. The development of kindling was more
      strongly suppressed in AAV-Homer1a-microinjected Npas4KO mice than in AAV-EGFP
      microinjected Npas4KO mice. These results indicate that Npas4 functions as a
      molecular switch to initiate homeostatic scaling and the targeting of Npas4
      Homer1a signaling may provide new approaches for the treatment of epilepsy.

PMID- 29222952
TI  - Accumulation of the coumarin scopolin under abiotic stress conditions is mediated
      by the Arabidopsis thaliana THO/TREX complex.
AB  - Secondary metabolites are involved in the plant stress response. Among these are
      scopolin and its active form scopoletin, which are coumarin derivatives
      associated with reactive oxygen species scavenging and pathogen defence. Here we
      show that scopolin accumulation can be induced in the root by osmotic stress and
      in the leaf by low-temperature stress in Arabidopsis thaliana. A genetic screen
      for altered scopolin levels in A. thaliana revealed a mutant compromised in
      scopolin accumulation in response to stress; the lesion was present in a
      homologue of THO1 coding for a subunit of the THO/TREX complex. The THO/TREX
      complex contributes to RNA silencing, supposedly by trafficking precursors of
      small RNAs. Mutants defective in THO, AGO1, SDS3 and RDR6 were impaired with
      respect to scopolin accumulation in response to stress, suggesting a mechanism
      based on RNA silencing such as the trans-acting small interfering RNA pathway,
      which requires THO/TREX function.

PMID- 29222953
TI  - Bacterial community changes in copper and PEX drinking water pipeline biofilms
      under extra disinfection and magnetic water treatment.
AB  - AIMS: To study the stability of biofilms and water quality in pilot scale
      drinking water copper and PEX pipes in changing conditions (extra disinfection,
      magnetic water treatment, MWT). METHODS AND RESULTS: Next-generation sequencing
      (NGS) of 16S ribosomal RNA genes (rDNA) to describe total bacterial community and
      ribosomal RNA (rRNA) to describe active bacterial members in addition to
      traditional microbiological methods were applied. Biofilms from control copper
      and PEX pipes shared same most abundant bacteria (Methylobacterium spp.,
      Sphingomonas spp., Zymomonas spp.) and average species diversities (Shannon 3.8
      4.2) in rDNA and rRNA libraries, whereas few of the taxa differed by their
      abundance such as lower total Mycobacterium spp. occurrence in copper (<0.02%) to
      PEX (<0.2%) pipes. Extra disinfection (total chlorine increase from c. 0.5 to 1
      mg l-1 ) affected total and active population in biofilms seen as decrease in
      many bacterial species and diversity (Shannon 2.7, P < 0.01, rRNA) and increase
      in Sphingomonas spp. as compared to control samples. Furthermore, extra
      disinfected copper and PEX samples formed separate clusters in unweighted non
      metric multidimensional scaling plot (rRNA) similarly to MWT-treated biofilms of
      copper (but not PEX) pipes that instead showed higher species diversity (Shannon
      4.8, P < 0.05 interaction). CONCLUSIONS: Minor chlorine dose addition increased
      selection pressure and many species were sensitive to chlorination. Pipe material
      seemed to affect mycobacteria occurrence, and bacterial communities with MWT in
      copper but not in PEX pipes. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      using rRNA showed that chlorination affects especially active fraction of
      bacterial communities. Copper and PEX differed by the occurrence of some
      bacterial members despite similar community profiles.

PMID- 29222954
TI  - Evaluation of motion artifact metrics for coronary CT angiography.
AB  - PURPOSE: This study quantified the performance of coronary artery motion artifact
      metrics relative to human observer ratings. Motion artifact metrics have been
      used as part of motion correction and best-phase selection algorithms for
      Coronary Computed Tomography Angiography (CCTA). However, the lack of ground
      truth makes it difficult to validate how well the metrics quantify the level of
      motion artifact. This study investigated five motion artifact metrics, including
      two novel metrics, using a dynamic phantom, clinical CCTA images, and an observer
      study that provided ground-truth motion artifact scores from a series of pairwise
      comparisons. METHOD: Five motion artifact metrics were calculated for the
      coronary artery regions on both phantom and clinical CCTA images: positivity,
      entropy, normalized circularity, Fold Overlap Ratio (FOR), and Low-Intensity
      Region Score (LIRS). CT images were acquired of a dynamic cardiac phantom that
      simulated cardiac motion and contained six iodine-filled vessels of varying
      diameter and with regions of soft plaque and calcifications. Scans were repeated
      with different gantry start angles. Images were reconstructed at five phases of
      the motion cycle. Clinical images were acquired from 14 CCTA exams with patient
      heart rates ranging from 52 to 82 bpm. The vessel and shading artifacts were
      manually segmented by three readers and combined to create ground-truth artifact
      regions. Motion artifact levels were also assessed by readers using a pairwise
      comparison method to establish a ground-truth reader score. The Kendall's Tau
      coefficients were calculated to evaluate the statistical agreement in ranking
      between the motion artifacts metrics and reader scores. Linear regression between
      the reader scores and the metrics was also performed. RESULTS: On phantom images,
      the Kendall's Tau coefficients of the five motion artifact metrics were 0.50
      (normalized circularity), 0.35 (entropy), 0.82 (positivity), 0.77 (FOR),
      0.77(LIRS), where higher Kendall's Tau signifies higher agreement. The FOR, LIRS,
      and transformed positivity (the fourth root of the positivity) were further
      evaluated in the study of clinical images. The Kendall's Tau coefficients of the
      selected metrics were 0.59 (FOR), 0.53 (LIRS), and 0.21 (Transformed positivity).
      In the study of clinical data, a Motion Artifact Score, defined as the product of
      FOR and LIRS metrics, further improved agreement with reader scores, with a
      Kendall's Tau coefficient of 0.65. CONCLUSION: The metrics of FOR, LIRS, and the
      product of the two metrics provided the highest agreement in motion artifact
      ranking when compared to the readers, and the highest linear correlation to the
      reader scores. The validated motion artifact metrics may be useful for developing
      and evaluating methods to reduce motion in Coronary Computed Tomography
      Angiography (CCTA) images.

PMID- 29222955
TI  - Brain comorbidities in normal pressure hydrocephalus.
AB  - BACKGROUND AND PURPOSE: This cross-sectional study aims to compare gait changes
      after the cerebrospinal fluid (CSF) tap test between normal pressure
      hydrocephalus patients with and without brain comorbidities (NPH+ and NPH-
      respectively) and then to identify significant contributors to a poor CSF tap
      test amongst individuals with NPH+. METHODS: Gait changes (during the single task
      and the dual task of backward counting) were quantified before and 24 h after the
      CSF tap test with an optoelectronic system in 52 NPH patients (77.4 +/- 6.0
      years; 34.6% women). Changes after the CSF tap test in stride time variability
      (STV, %) were our main outcome. CSF Alzheimer's disease biomarkers,
      cerebrovascular white matter changes assessed with brain imaging and
      neurodegenerative diseases with parkinsonian syndrome represented the three
      individual brain comorbidities. RESULTS: Brain comorbidities were frequently
      identified, NPH+ patients representing 40 patients of our sample (76.9%). NPH-
      patients improved their STV better in the single task (delta of STV = -58.6% +/-
      54.3% vs. -14.1% +/- 62.0%; P = 0.031) and in the dual task (delta of STV =-32.2%
      +/- 33.7% vs. 6.3% +/- 58.4%; P = 0.028) after the CSF tap test than NPH+
      patients. Amongst NPH+ individuals, only comorbid Alzheimer's disease was
      associated with STV increase (i.e. deterioration of gait) in the dual task [beta
      38.4; 95% confidence interval (5.64; 71.24); P = 0.023] after the CSF tap test,
      whilst it was borderline in the single task [beta 35.0; 95% confidence interval (
      1.97; 71.90); P = 0.063]. CONCLUSIONS: Brain comorbidities affect gait
      improvement after the CSF tap test in NPH patients; this influence is driven by
      Alzheimer's disease-related pathology.

PMID- 29222956
TI  - Demographic drivers of a refugee species: large-scale experiments guide
      strategies for reintroductions of hirola.
AB  - Effective reintroduction strategies require accurate estimates of vital rates and
      the factors that influence them. The hirola (Beatragus hunteri) is the rarest
      antelope on Earth, with a global population size of <500 individuals restricted
      to the Kenya-Somali border. We estimated vital rates of hirola populations
      exposed to varying levels of predation and rangeland quality from 2012 to 2015,
      and then built population matrices to estimate the finite rate of population
      change (lambda) and demographic sensitivities. Mean survival for all age classes
      and population growth was highest in the low-predation-high-rangeland-quality
      setting (lambda = 1.08 +/- 0.03 [mean +/- SE]), and lowest in the high-predation
      low-rangeland-quality setting (lambda = 0.70 +/- 0.22). Retrospective demographic
      analyses revealed that increased fecundity (the number of female calves born to
      adult females annually) and female calf survival were responsible for higher
      population growth where large carnivores were absent. In contrast, variation in
      adult female survival was the primary contributor to differences in population
      growth attributable to rangeland quality. Our analyses suggest that hirola
      demography is driven by a combination of top-down (predation) and bottom-up
      (rangeland quality) forces, with populations in the contemporary geographic range
      impacted both by declining rangeland quality and predation. To enhance the
      chances of successful reintroductions, conservationists can consider rangeland
      restoration to boost both the survival and fecundity of adult females within the
      hirola's historical range.

PMID- 29222957
TI  - Association between beta-cell function estimated by HOMA-beta and prognosis of
      non-diabetic patients with ischaemic stroke.
AB  - BACKGROUND AND PURPOSE: Studies showed that beta-cell dysfunction is associated
      with increased risk of cardiovascular disease and subclinical carotid
      atherosclerosis. This study aimed to investigate the association between beta
      cell function and prognosis of non-diabetic patients with ischaemic stroke.
      METHODS: Ischaemic stroke patients without diabetes in the Abnormal Glucose
      Regulation in Patients with Acute Stroke across China registry were included in
      this analysis. Homeostasis assessment of beta-cell function (HOMA-beta) was
      performed and classified into four groups according to quartiles. The outcomes
      included stroke recurrence, poor functional outcome and all-cause mortality.
      RESULTS: In a total of 1244 patients, the average age was 62.3 years; 63.1%
      patients were male. At 1 year, the first quartile of HOMA-beta (<54.0) was
      associated with increased stroke recurrence (adjusted hazard ratio 2.04, 95%
      confidence interval 1.32-3.17, P = 0.001), poor functional outcome (adjusted odds
      ratio 3.04, 95% confidence interval 1.90-4.88, P < 0.001) and mortality (adjusted
      hazard ratio 4.12, 95% confidence interval 2.24-7.59, P < 0.001) compared with
      the fourth quartile of HOMA-beta (>=166.3) after adjustment for insulin
      resistance and other potential covariates. The second and third quartiles of HOMA
      beta were significantly associated with an increased risk of poor functional
      outcome. Multivariable regression analysis with restricted cubic splines showed
      an L-shaped association between HOMA-beta and outcomes at 1 year. CONCLUSIONS:
      Our study shows that lower HOMA-beta level is associated with poor outcomes at 1
      year in non-diabetic patients with ischaemic stroke.

PMID- 29222958
TI  - The prevalence and odds of depression in patients with vitiligo: a meta-analysis.
AB  - OBJECTIVE: The objective of this study was to provide a pooled estimate of the
      prevalence and odds of depression in patients with vitiligo. METHODS: A
      systematic literature search of Medline, Embase and Cochrane library databases
      was conducted. The proportions and mean questionnaire values for depression were
      pooled according to different evaluation methods. In controlled studies, odds
      ratio and standardized mean differences compared depression in vitiligo patients
      with healthy controls. RESULTS: One thousand nine hundred and sixty-five patients
      were identified from 20 eligible cohorts to be included in the present meta
      analysis review. Sample sizes ranged from 30 to 308 for each analysis. The pooled
      prevalence of depression across 17 unique populations (n = 1711) was 29% (95% CI
      20-39). The prevalence of clinical depression was 8% (95% CI 2%-14%) using
      Diagnostic and Statistical Manual of Mental Disorders IV or International
      Classification of Diseases codes-10, and the prevalence of depressive symptoms
      was 33% (95% CI 23%-44%) using validated screening inventory and rating scales.
      Patient with vitiligo was 4.96 times more likely to display depression compared
      with controls. Subgroup analysis showed that the prevalence of depression in
      Asian and female patients with vitiligo was significantly higher than that in
      Caucasian and male ones. The pooled prevalence of depressive symptoms was higher
      (56%, 95% CI 0.5-0.62), and the heterogeneity was lowering cases with Hamilton
      Depression Rating Scale (HDRS) questionnaire when compared with other
      questionnaires. CONCLUSIONS: This meta-analysis review indicates that the
      prevalence of depression is high in patients with vitiligo. The HDRS
      questionnaire may be the most sensitive tool for testing the depressive symptoms
      among patients with vitiligo.

PMID- 29222959
TI  - Development of depth encoding small animal PET detectors using dual-ended readout
      of pixelated scintillator arrays with SiPMs.
AB  - PURPOSE: The performance of current small animal PET scanners is mainly limited
      by the detector performance and depth encoding detectors are required to develop
      PET scanner to simultaneously achieve high spatial resolution and high
      sensitivity. Among all depth encoding PET detector approaches, dual-ended readout
      detector has the advantage to achieve the highest depth of interaction (DOI)
      resolution and spatial resolution. Silicon photomultiplier (SiPM) is believed to
      be the photodetector of the future for PET detector due to its excellent
      properties as compared to the traditional photodetectors such as photomultiplier
      tube (PMT) and avalanche photodiode (APD). The purpose of this work is to develop
      high resolution depth encoding small animal PET detector using dual-ended readout
      of finely pixelated scintillator arrays with SiPMs. METHODS: Four lutetium
      yttrium oxyorthosilicate (LYSO) arrays with 11 * 11 crystals and 11.6 * 11.6 * 20
      mm3 outside dimension were made using ESR, Toray and BaSO4 reflectors. The LYSO
      arrays were read out with Hamamatsu 4 * 4 SiPM arrays from both ends. The SiPM
      array has a pixel size of 3 * 3 mm2 , 0.2 mm gap in between the pixels and a
      total active area of 12.6 * 12.6 mm2 . The flood histograms, DOI resolution,
      energy resolution and timing resolution of the four detector modules were
      measured and compared. RESULTS: All crystals can be clearly resolved from the
      measured flood histograms of all four arrays. The BaSO4 arrays provide the best
      and the ESR array provides the worst flood histograms. The DOI resolution
      obtained from the DOI profiles of the individual crystals of the four array is
      from 2.1 to 2.35 mm for events with E > 350 keV. The DOI ratio variation among
      crystals is bigger for the BaSO4 arrays as compared to both the ESR and Toray
      arrays. The BaSO4 arrays provide worse detector based DOI resolution. The
      photopeak amplitude of the Toray array had the maximum change with depth, it
      provides the worst energy resolution of 21.3%. The photopeak amplitude of the
      BaSO4 array with 80 MUm reflector almost doesn't change with depth, it provides
      the best energy resolution of 12.9%. A maximum timing shift of 1.37 ns to 1.61 ns
      among the corner and the center crystals in the four arrays was obtained due to
      the use of resistor network readout. A crystal based timing resolution of 0.68 ns
      to 0.83 ns and a detector based timing resolution of 1.26 ns to 1.45 ns were
      obtained for the four detector modules. CONCLUSIONS: Four high resolution depth
      encoding small animal PET detectors were developed using dual-ended readout of
      pixelated scintillator arrays with SiPMs. The performance results show that those
      detectors can be used to build a small animal PET scanner to simultaneously
      achieve uniform high spatial resolution and high sensitivity.

PMID- 29222960
TI  - Drug-induced acute liver failure in children and adults: Results of a single
      centre study of 128 patients.
AB  - BACKGROUND & AIMS: Drugs producing acute liver failure (ALF) are uncommon and
      vary geographically. Here we review the implicated drugs, clinical features,
      laboratory characteristics and outcome of patients with drug-induced ALF (DIALF).
      We analysed the predictors of mortality and their relationship with MELD, King's
      College criteria (KCC) and ALFSG prognostic index. METHODS: We identified DIALF
      patients from our drug-induced liver injury (DILI) registry (1997-2017). RUCAM
      was used for case adjudication. Patients who fulfilled criteria for acute liver
      failure and drug-induced liver injury were included. Primary outcome measure was
      spontaneous survival or death. RESULTS: There were 128 cases of DIALF (14%) among
      905 patients with DILI. Mean age was 38 years, 68 (53%) female and 21(16.4%)
      children <18 years. Combination anti-TB drugs (ATD) (n = 92, 72.4%) accounted for
      a majority of DIALF. Others were anti-epileptic drugs (AED, n = 11, 10%), dapsone
      (n = 7, 5.5%), hormones (n = 2), ferrous sulphate overdose (n = 2), acetaminophen
      (APAP) (n = 2), antiretroviral (n = 2), CAM (N = 2), chemotherapy agents (N = 3),
      amoxicillin-clavulanic acid (n = 2) and others (n = 3). Forty-four patients (34%)
      recovered spontaneously and 84(66%) including 13 children (62%) died. Females,
      ascites, albumin, bilirubin, INR and MELD were significantly associated with
      mortality. Mortality was 79% for ATD and 100% for APAP and iron overdose. Area
      under ROC was 0.76 for MELD and ALFSG index and 0.51 for KCC. CONCLUSIONS:
      Fourteen percent of DILI resulted in DIALF. ATD, AED, dapsone and antiretroviral
      drugs are most common agents. Spontaneous survival was only 34% with an even
      higher mortality with ATD. Non-ATD and non-APAP drugs had a better survival
      (51%).INR and MELD predicted mortality.

PMID- 29222961
TI  - Liver zonation in children with non-alcoholic fatty liver disease: Associations
      with dietary fructose and uric acid concentrations.
AB  - BACKGROUND & AIMS: As dietary components are delivered directly to the periportal
      zone of the liver lobule, there is the potential for greater injury in this zone
      (zone 1) compared to the perivenous zone (zone 3). We investigated the
      associations between dietary fructose consumption and uric acid concentrations
      and differential zonal injury in periportal and perivenous zones. METHODS: A
      total of 271 children's histological images were scored in 5 periportal and 5
      perivenous zones for steatosis, ballooning, inflammation and fibrosis severity.
      Dietary fructose consumption (g/d) was assessed and uric acid measured in serum.
      Logistic regression was undertaken to test associations between both high
      fructose consumption and hyperuricaemia, and histological disease in periportal
      and perivenous zones. RESULTS: Children with a mean age of 12.5 years were
      included in the study. Inflammation (mean +/- SD) was increased in the periportal
      vs perivenous zones (0.78 +/- 0.43 vs 0.41 +/- 0.48, P = .041). There were non
      significant trends towards greater steatosis, ballooning and fibrosis in the
      periportal zone. In the fully adjusted models, high fructose intake was
      associated with disease in both zones. Example for periportal and perivenous
      zones, respectively, steatosis 1.56 (1.12, 2.49) and 1.21 (1.09, 2.73);
      inflammation 4.29 (2.31, 5.88) and 3.69 (2.14, 4.56); and fibrosis 2.72 (1.43,
      3.76) and 1.96 (1.24, 2.37). Hyperuricaemia (uric acid >=5.9 mg/dL) was
      associated with inflammation in the periportal zone 1.71 (1.17, 2.35); and was
      associated with steatosis and fibrosis in both zones; for example, for periportal
      and perivenous zones, respectively, steatosis 2.98 (1.65, 3.23) and 1.14 (1.05,
      1.99); and fibrosis, 2.65 (1.35, 2.99) and 1.31 (1.13, 2.17). CONCLUSIONS: High
      fructose consumption is associated with disease severity in both lobular zones
      and hyperuricaemia may be associated with more severe disease in the periportal
      zone.

PMID- 29222962
TI  - East meets West: historical investigation of non-operative biliary interventions.

PMID- 29222964
TI  - East meets West: East and West pioneers of "anatomical right hepatectomy" -
      period of dawn to establishment.

PMID- 29222963
TI  - Preoperative biliary drainage adversely affects surgical outcomes in
      periampullary cancer: a retrospective and propensity score-matched analysis.
AB  - BACKGROUND: The use of preoperative biliary drainage (PBD) for managing patients
      with periampullary cancer awaiting surgery remains controversial. The impact of
      PBD status and type on surgical outcomes has not been established, leading to a
      lack of consensus. We aimed to evaluate the impact of PBD on short-term surgical
      outcomes in curatively resected periampullary cancer. METHODS: We retrospectively
      reviewed data from patients undergoing curative periampullary cancer resection. A
      propensity score-matched analysis was performed to adjust for clinical
      differences. Univariate and multivariate analyses were performed to determine
      independent risk factors for complications. RESULTS: The overall complication
      rate was significantly higher in patients who underwent PBD (P = 0.027).
      Additionally, complication rates were significantly higher in the endoscopic
      biliary drainage (EBD) group than in the percutaneous transhepatic biliary
      drainage (PTBD) group (P < 0.001). After propensity score matching, overall
      complication rates in patients receiving EBD (P < 0.001) were significantly
      higher. PBD type and diagnosis were independent risk factors for complications
      (hazard ratios: 1.927 for EBD; 1.921 for biliary tract cancer). CONCLUSIONS:
      Preoperative biliary drainage, especially EBD, should not be routinely performed
      in patients awaiting surgery for periampullary cancer, as it increases the risk
      of complications.

PMID- 29222965
TI  - Co-existence of myeloid neoplasm and monoclonal gammopathy; case series and
      review of literature.

PMID- 29222966
TI  - Optimizing Functional Outcomes in Mandibular Condyle Reconstruction With the Free
      Fibula Flap Using Computer-Aided Design and Manufacturing Technology.
AB  - PURPOSE: Mandibular defects involving the condyle represent a complex
      reconstructive challenge for restoring proper function of the temporomandibular
      joint (TMJ) because it requires precise bone graft alignment for full restoration
      of joint function. The use of computer-aided design and manufacturing (CAD/CAM)
      technology can aid in accurate reconstruction of mandibular condyle defects with
      a vascularized free fibula flap without the need for additional adjuncts. The
      purpose of this study was to analyze clinical and functional outcomes after
      reconstruction of mandibular condyle defects using only a free fibula graft with
      the help of virtual surgery techniques. MATERIALS AND METHODS: A retrospective
      review was performed to identify all patients who underwent mandibular
      reconstruction with only a free fibula flap without any TMJ adjuncts after a
      total condylectomy. Three-dimensional modeling software was used to plan and
      execute reconstruction for all patients. RESULTS: From 2009 through 2014, 14
      patients underwent reconstruction of mandibular defects involving the condyle
      with the aid of virtual surgery technology. The average age was 38.7 years
      (range, 11 to 77 yr). The average follow-up period was 2.6 years (range, 0.8 to
      4.2 yr). Flap survival was 100% (N = 14). All patients reported improved facial
      symmetry, adequate jaw opening, and normal dental occlusion. In addition, they
      achieved good functional outcomes, including normal intelligible speech and the
      tolerance of a regular diet with solid foods. Maximal interincisal opening range
      for all patients was 25 to 38 mm with no lateral deviation or subjective joint
      pain. No patient had progressive joint hypomobility or condylar migration. One
      patient had ankylosis, which required release. CONCLUSION: TMJ reconstruction
      poses considerable challenges in bone graft alignment for full restoration of
      joint function. The use of CAD/CAM technology can aid in accurate reconstruction
      of mandibular condyle defects with a vascularized free fibula flap through
      precise planning and intraoperative manipulation with optimal functional
      outcomes.

PMID- 29222968
TI  - Student-teacher relationships and bullying: The role of student social status.
AB  - Student-teacher relationships have been shown to influence bullying-related
      behaviors in students. This study considered the moderating role of students'
      social statuses in the classroom. The study sample included 435 students (48.7%
      females) taken from 18 Italian middle-school classrooms (i.e., sixth to eighth
      grade). A multigroup path analysis approach was employed to examine whether the
      effects of the student-teacher relationships on bullying-related behaviors
      differed among social statuses. The results showed that perceived conflict with
      the teacher was shown to have a significant positive effect on students'
      engagement in active bullying for students from all the statuses, except for
      neglected students. In particular, this effect was more relevant for rejected
      students. The results showed that social status and student-teacher relationships
      integrate and shed light on which roles are taken by young adolescents in school
      bullying, highlighting that it is important for the teachers to recognize these
      students.

PMID- 29222967
TI  - Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide
      by enteral dextrose improves glucose homeostasis and inflammation in murine
      endotoxemia.
AB  - Loss of glucose homeostasis during sepsis is associated with increased organ
      dysfunction and higher mortality. Novel therapeutic strategies to promote
      euglycemia in sepsis are needed. We have previously shown that early low-level
      intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces
      insulin resistance in septic mice, resulting in profound hyperglycemia and
      worsened systemic inflammation. In this study, we hypothesized that
      administration of low-level dextrose via the enteral route would stimulate
      intestinal incretin hormone production, potentiate insulin secretion in a glucose
      dependent manner, and thereby improve glycemic control in the acute phase of
      sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice
      exposed to bacterial endotoxin and measured incretin hormone release, glucose
      disposal, and proinflammatory cytokine production. Compared with IV
      administration, enteral dextrose increased circulating levels of the incretin
      hormone glucose-dependent insulinotropic peptide (GIP) associated with increased
      insulin release and insulin sensitivity, improved mean arterial pressure, and
      decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued
      glucose metabolism, improved blood pressure, and increased insulin release in
      endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP
      signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation
      of endogenous GIP secretion by early enteral dextrose maintains glucose
      homeostasis and attenuates the systemic inflammatory response in endotoxemic mice
      and may provide a therapeutic target for improving glycemic control and clinical
      outcomes in patients with sepsis.

PMID- 29222969
TI  - Copper(II) complexes of N3O tripodal ligands appended with pyrene and polyamine
      groups: Anti-proliferative and nuclease activities.
AB  - A series of tripodal ligands based on the 2-tert-butyl-4-R-6-phenol was
      synthesized, where R=aldehyde (HL1), R=putrescine-pyrene (HL2) and R=putrescine
      (HL3). A dinucleating ligand wherein a putrescine group connects two tripodal
      moieties was also prepared (H2L4). The corresponding copper complexes (1, 2, 3,
      and 4, respectively) were prepared and characterized. We determined the phenol's
      pKas in the range 2.47-3.93. The DNA binding constants were determined at 6*106,
      5.5*105 and 2.7*106 for 2, 3 and 4, respectively. The complexes display a metal
      centered reduction wave at Epc,red=-0.45 to -0.5V vs. saturated calomel
      electrode, as well as a ligand-centered oxidation wave above 0.57V at pH7. In the
      presence of ascorbate they promote an efficient cleavage of DNA, with for example
      a concentration required to cleave 50% of supercoiled DNA of 1.7MUM for 2. The
      nuclease activity is affected by the nature of the R group: putrescine-pyrene~bis
      ligating>putrescine>aldehyde. The species responsible for strand scission is the
      hydroxyl radical. The cytotoxicity of the complexes was evaluated on bladder
      cancer cell lines sensitive or resistant to cis-platin. The IC50 of complexes 2
      and 4 span over a short range (1.3-2MUM) for the two cell lines. They are lower
      than those of the other complexes (3.1-9.7MUM) and cis-platin. The most active
      compounds block the cell cycle at the G0/1 phase and promote apoptosis.

PMID- 29222970
TI  - Relaxation of structural constraints during Amicyanin unfolding.
AB  - We study the thermal unfolding of amicyanin by quantifying the resiliency of the
      native state to structural perturbations. Three signatures characterizing stages
      of unfolding are identified. The first signature, lateral extension of the
      polypeptide chain, is calculated directly from the reported crystallographic
      data. Two other signatures, the radial displacement of each residue from Cu(II)
      and the angular spread in the chain as the protein unfolds, are calculated using
      crystallographic data in concert with a geometrical model we introduced
      previously (J.J. Kozak, H. B. Gray, R. A. Garza-Lopez, J. Inorg. Biochem.
      155(2016) 44-55). Particular attention is paid to the resiliency of the two beta
      sheets in amicyanin. The resiliency of residues in the near neighborhood of the
      Cu center to destabilization provides information on the persistence of the
      entatic state. Similarly, examining the resiliency of residues intercalated
      between structured regions (beta sheets, the alpha helix) provides a basis for
      identifying a "hydrophobic core." A principal focus of our study is to compare
      results obtained using our geometrical model with the experimental results (C. La
      Rosa, D. Milardi, D. M. Grasso, M. P. Verbeet, G. W. Canters, L. Sportelli, R.
      Guzzi, Eur. Biophy. J.30(8),(2002) 559-570) on the denaturation of amicyanin, and
      we show that our results support a classical model proposed by these authors.

PMID- 29222971
TI  - The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic
      polymorphisms on executive function in adolescents with discrete patterns of
      childhood adversity.
AB  - PURPOSE: Catechol-O-methyltransferase (COMT) Val158Met functional polymorphisms
      play a crucial role in the development of executive function (EF), but their
      effect may be moderated by environmental factors such as childhood adversity. The
      present study aimed at testing the divergent impact of the COMT Val158Met
      genotype on EF in non-clinical adolescents with discrete patterns of childhood
      adversity. METHODS: A total of 341 participants completed the Childhood Trauma
      Questionnaire, the self-reported version of the Behavior Rating Inventory of
      Executive Function, and self-administered questionnaires on familial function.
      The participants' COMT Val158Met genotype was determined. Associations among the
      variables were explored using latent class analysis and general linear models.
      RESULTS: We found that Val/Val homozygotes showed significantly worse performance
      on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial
      eta2=0.018). Moreover, three typical patterns of childhood adversity, namely, low
      childhood adversity (23.5%), childhood neglect (59.8%), and high childhood
      adversity (16.7%), were found. Both childhood neglect and high childhood
      adversity had a negative impact on each aspect of EF and on global EF
      performance. Importantly, these results provided evidence for significant
      interaction effects, as adolescents with the Val/Val genotype showed inferior
      behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial
      eta2=0.020) in the presence of high childhood adversity. Furthermore, there were
      no differences between the genotypes for childhood neglect and low childhood
      adversity. CONCLUSIONS: Overall, this is the first study to show that an
      interaction between the COMT genotype and childhood adversity affects EF in non
      clinical adolescents. These results suggest that the COMT genotype may operate as
      a susceptibility gene vulnerable to an adverse environment.

PMID- 29222972
TI  - Factors associated with adverse pregnancy outcomes in women with systematic lupus
      erythematosus.
AB  - The aim of this prospective study was to determine clinical factors associated
      with adverse pregnancy outcomes in women with systematic lupus erythematosus
      (SLE). Fifty-six pregnancies from 46 women with SLE were enrolled. Risk factors
      for pregnancy loss, premature delivery, hypertensive disorders of pregnancy
      (HDP), and light-for-date neonate (LFD), were evaluated. Univariate and
      multivariate logistic regression analyses revealed a history of two or more
      pregnancy losses before 10 gestational weeks (GW) (OR 11.5, 95%CI 1.72-76.8) as a
      risk factor for pregnancy loss; low levels of blood complements (OR 7.55, 95%CI
      1.10-51.9) and antiphospholipid syndrome (OR 26.5, 95%CI 3.17-219) as risk
      factors for premature delivery before 37 GW; SLEDAI score at conception (OR 1.68,
      95%CI 1.05-2.68) and positive tests for two or more antiphospholipid antibodies
      (OR 6.89, 95%CI 1.13-41.9) as risk factors for premature delivery before 34 GW;
      prednisolone therapy >14mg/day (OR 7.55, 95%CI 1.10-51.9) as a risk factor for
      HDP; and low dose aspirin therapy (OR 0.21, 95%CI 0.05-0.97) decreased the risk
      for LFD neonate. These results have important implications for clinicians
      managing SLE complicated pregnancy.

PMID- 29222973
TI  - Utilisation of academic nursing competence in Europe - A survey among members of
      the European Academy of Nursing Science.
AB  - BACKGROUND: In line with national and international strategies in Europe, the
      number of nurses with a doctoral degree has increased. The European Academy of
      Nursing Science (EANS) has for 18years delivered a three-year doctoral summer
      school for nurses. Questions have been raised in terms of how academic nurses'
      competencies are used and in what positions. AIM: To understand the progression
      of nurses' academic careers following completion of the EANS Summer School and to
      picture how research and academic skills of the nurses are being used for
      research and/or other fields in nursing. METHODS: We commenced a cross-sectional
      survey. Former EANS Summer School participants were invited to take part in the
      online survey with questions developed specifically for this study. The study
      conformed to the principle of good clinical research practice and was reviewed
      and approved by the EANS Board. RESULTS: Of 380 former participants, 308 were
      eligible for participating in the survey. A total of 140 (45%) responded. The
      respondents originated from 21 countries. Sixty-nine percent had their main
      position in universities or university colleges and 25% in healthcare
      organisations. More than 80% were involved in research, teaching and supervision,
      and 26% were involved in direct client/patients care while 71% reported doing
      postdoctoral research where descriptive research designs dominated. The research
      topics covered a large variety of aspects in clinical nursing, education,
      development and theory. CONCLUSION: The EANS Summer School is an example of an
      effort to improve nurses' academic competencies. The survey indicates that the
      competencies of academically trained nurses in Europe primarily are used in
      universities and educational institutions. However, a large proportion is working
      close to and in collaboration with clinical practice. Evidence of the legacy of
      having undergone the EANS Summer School includes using advanced research methods
      and collaboration with the international EANS network.

PMID- 29222974
TI  - Cold atmospheric plasma (CAP), a novel physicochemical source, induces neural
      differentiation through cross-talk between the specific RONS cascade and
      Trk/Ras/ERK signaling pathway.
AB  - Plasma, formed by ionization of gas molecules or atoms, is the most abundant form
      of matter and consists of highly reactive physicochemical species. In the physics
      and chemistry fields, plasma has been extensively studied; however, the exact
      action mechanisms of plasma on biological systems, including cells and humans,
      are not well known. Recent evidence suggests that cold atmospheric plasma (CAP),
      which refers to plasma used in the biomedical field, may regulate diverse
      cellular processes, including neural differentiation. However, the mechanism by
      which these physicochemical signals, elicited by reactive oxygen and nitrogen
      species (RONS), are transmitted to biological system remains elusive. In this
      study, we elucidated the physicochemical and biological (PCB) connection between
      the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural
      differentiation. Excited atomic oxygen in the plasma phase led to the formation
      of RONS in the PCB network, which then interacted with reactive atoms in the
      extracellular liquid phase to form nitric oxide (NO). Production of large amounts
      of superoxide radical (O2-) in the mitochondria of cells exposed to CAP
      demonstrated that extracellular NO induced the reversible inhibition of
      mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide,
      formed by O2- dismutation, act as an intracellular messenger to specifically
      activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate
      the mechanism linking physicochemical signals from the CAP cascade to the
      intracellular neural differentiation signaling pathway, providing physical,
      chemical and biological insights into the development of therapeutic techniques
      to treat neurological diseases.

PMID- 29222975
TI  - Hydrothermal synthesis of hierarchical CoO/SnO2 nanostructures for ethanol gas
      sensor.
AB  - In this work, ethanol gas sensor with high performance was fabricated
      successfully with hierarchical CoO/SnO2 heterojunction by two-steps hydrothermal
      method. The response value of CoO/SnO2 sensor is up to 145 at 250  degrees C when
      exposed to 100 ppm ethanol gas, which is much higher than that (13.5) of SnO2
      sensor. These good sensing performances mainly attribute to the formation of the
      CoO/SnO2 heterojunction, which makes great variation of resistance in air and
      ethanol gas. Thus, the combination of n-type SnO2 and p-type CoO provides an
      effective strategy to design new ethanol gas sensors. The unique nanostructure
      also played an important role in detecting ethanol, due to its contribution in
      facilitating the transport rate of the ethanol gas molecules. Also, we provide a
      general two-step strategy for designing the heterojunction based on the SnO2
      nanostructure.

PMID- 29222976
TI  - Enhanced electrocatalytic activity and stability of monodisperse Pt
      nanocomposites for direct methanol fuel cells.
AB  - Direct methanol fuel cells (DMFCs) are one of the most important fuel cells
      operating at low temperature using methanol as fuel and they need very efficient
      catalysts to activate the methanol. Generally, the most efficient fuel cell
      catalysts are platinum-based nanoparticles that can be used by different
      supporting materials such as different as prepared and functionalized carbon
      derivatives. For this purpose, herein, the carbon black has been mainly
      functionalized with an acidification process in order to increase the electrical
      conductivity and heterogeneous electron transfer rate of supporting materials.
      After functionalization of carbon black (f-CB), platinum salt (PtCl4) was
      stabilized with propylamine (PA) in the presence of ethylene glycol (EG) and f-CB
      by microwave synthesis method. XPS, XRD, TEM and Raman Spectroscopy techniques
      were used to determine the morphology of the prepared catalyst. The results
      showed that the prepared nanocatalyst has face-centered cubic (fcc) structure and
      uniformly distribution on supporting material. Besides, chronoamperometry (CA)
      and cyclic voltammetry (CV) techniques were used to determine the electrochemical
      activity of functionalized carbon black supported Pt NPs (Pt/f-CB) towards
      methanol. From the results obtained from the CV and CA, it was found that the
      activity of the Pt/f-CB NPs (50 mA/cm2) was almost 4-5 times higher than that of
      the Pt/CB NPs and commercial available Pt/C catalyst (ETEK).

PMID- 29222977
TI  - Ultra-deep adsorptive desulfurization of fuels on cobalt and molybdenum
      nanoparticles loaded on activated carbon derived from waste rubber.
AB  - The role of cobalt and molybdenum nanoparticles loaded on activated carbon (AC)
      on the adsorptive desulfurization ability of sulfur-containing compounds was
      investigated under ambient conditions. The AC was first synthesized and
      activated, followed by incorporation of the cobalt (Co), molybdenum (Mo) and both
      Co and Mo nanoparticles. The adsorption activity parameters of the developed
      composites were determined using surface characterization and N2 physisorption
      techniques. The prepared composites were evaluated for simultaneous adsorption of
      sulfur compounds from fuels. The AC/CoMo composite showed better adsorption
      properties than pure AC, AC/Co and AC/Mo composites for the removal of thiophene
      (T), benzothiophene (BT), dibenzothiophene (DBT), 5-methyl-1-benzothiophene
      (MBT), 4,6-dimethyldibenzothiophene (DMDBT) and 4-methyldibenzothiophene (MDBT).
      The order of the thiophene compounds removal was found to be Thiophene < BT < DBT
      < MBT <= MDBT <= DMDBT. The enhanced desulfurization performance of the AC/CoMo
      composite was attributed to the increase in the surface area achieved through
      impregnation of both Co and Mo.

PMID- 29222978
TI  - Cobalt nanofibers coated with layered nickel silicate coaxial core-shell
      composites as excellent anode materials for lithium ion batteries.
AB  - A novel type of cobalt nanofibers coated with layered nickel silicate (Co
      nanofibers @ voids @ Ni3Si2O5(OH)4) coaxial core-shell composites were
      successfully prepared via a well-known Stober process and two hydrothermal
      methods. In the composites, the international nanosheet structure of the nickel
      silicate provided interlayer spaces for lithium ions in the process of insertion
      and extraction. The cobalt nanofibers served as a mechanical support for the
      nickel silicate nanosheets, which increased the electrical conductivity of the
      whole electrode. In addition, one-dimensional coaxial structure was stable to
      buffer the volume change and avoid the destruction of the structure. Moreover,
      the voids provided effective channels for the transportation of lithium ions. The
      Co nanofibers @ voids @ Ni3Si2O5(OH)4) coaxial core-shell composites presented
      superior electrochemical properties compared with the published Ni3Si2O5(OH)4
      related materials. With the advantages of exceptional performances and facile
      preparation, the composites show prospective application potential as advanced
      anode materials in lithium ion batteries.

PMID- 29222979
TI  - Hierarchical NiCo2O4 nanosheets grown on hollow carbon microspheres composites
      for advanced lithium-ion half and full batteries.
AB  - Hierarchical ultrathin NiCo2O4 nanosheeets grown on uniform hollow carbon
      microspheres (HC@NiCo2O4) are designed and fabricated by a solvothermal reaction
      followed with an annealing process. When evaluated as an anode for lithium ion
      batteries, the as-prepared HC@NiCo2O4 microspheres exhibit excellent
      electrochemical performance (a high reversible capacity of 1015 mA h g-1 after
      100 cycles at a current density of 0.1 A g-1 and a high capacity of 805 mA h g-1
      even at a high current density of 0.5 A g-1). By pairing with the LiCoO2 cathode,
      the HC@NiCo2O4 anode also manifests excellent performance in full cells. The
      outstanding electrochemical performance in half and full cells can be attributed
      to its unique structure, which can not only promote the contact of electrode and
      electrolyte during the charge and discharge processes, but also shorten the
      transmission path of electrons and ions. More importantly, this study inspires a
      better design of various metal oxide/carbon electrode materials for high
      performance lithium ion batteries.

PMID- 29222980
TI  - Bonding of doxorubicin to nanosilica and human serum albumin in various media.
AB  - Interaction of doxorubicin hydrochloride (DOX) (anti-cancer drug) with hydro
      compacted nanosilica A-300 (cA-300) alone or cA-300/human serum albumin (HSA) at
      a small content of water (h = 0.4 g per gram of dry silica) in different
      dispersion media (air, chloroform, and chloroform/trifluoroacetic acid) was
      analyzed using low-temperature 1H NMR spectroscopy, NMR cryoporometry and quantum
      chemistry to elucidate specific changes in the interfacial layers. Initial (bulk
      density rhob ~ 0.046 g/cm3) and hydro-compacted (rhob ~ 0.051-0.265 g/cm3 as a
      function of the hydration degree) nanosilicas were analyzed using nitrogen
      adsorption-desorption, gelatin adsorption, small angle X-ray scattering (SAXS),
      TEM, and infrared (FTIR) spectroscopy. Equilibrium adsorption of DOX onto cA-300
      and cA-300/HSA was analyzed using ultraviolet-visible light spectroscopy. Photon
      correlation spectroscopy was used to analyze the particle size distribution in
      aqueous suspensions with various contents of components. DOX more strongly bound
      to HSA than silica also affects structure of interfacial water layers that
      depends on dispersion media because chloroform as immiscible with water changes
      the water organization to enlarge water structures. In aqueous media, DOX alone
      remains mainly in the form of nano/microparticles (50 nm-2 um in size). However,
      with the presence of cA-300, cA-300/HSA, and HSA alone DOX transforms into pure
      nano-sized structures. These effects are explained by effective bonding of DOX to
      HSA having good transport properties with respect to drug molecules/ions that
      exceed similar properties of nanosilica alone, but cA-300/HSA can be a more
      effective composite as a drug carrier.

PMID- 29222981
TI  - Fabrication of biocompatible and efficient antimicrobial porous polymer surfaces
      by the Breath Figures approach.
AB  - We designed and fabricated highly efficient and selective antibacterial
      substrates, i.e. surface non-cytotoxic against mammalian cells but exhibiting
      strong antibacterial activity. For that purpose, microporous substrates (pore
      sizes in the range of 3-5 MUm) were fabricated using the Breath Figures approach
      (BFs). These substrates have additionally a defined chemical composition in the
      pore cavity (herein either a poly(acrylic acid) or the antimicrobial peptide
      Nisin) while the composition of the rest of the surface is identical to the
      polymer matrix. As a result, considering the differences in size of bacteria (1-4
      MUm) in comparison to mammalian cells (above 10 um) the bacteria were able to
      enter in contact with the inner part of the pores where the antimicrobial
      functionality has been placed. On the opposite, mammalian cells remain in contact
      with the top surface thus preventing cytotoxic effects and enhancing the
      biocompatibility of the substrates. The resulting antimicrobial surfaces were
      exposed to Staphylococcus aureus as a model bacteria and murine endothelial C166
      GFP cells. Superior antibacterial performance while maintaining an excellent
      biocompatibility was obtained by those surfaces prepared using PAA while no
      evidence of significant antibacterial activity was observed at those surfaces
      prepared using Nisin.

PMID- 29222982
TI  - Association between MTHFR variant and diabetic neuropathy.
AB  - BACKGROUND: Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an
      important role in the pathophysiology of diabetes and its complications due to
      its influence on plasma homocysteine levels and also its effect on scavenging
      peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most
      common diabetic chronic complications. The aim of this study was to investigate
      the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A /C
      polymorphisms. METHOD: Patients with type 2 diabetes N=248 were enrolled in the
      study, consisting of patients with neuropathy (N=141) and patients without
      neuropathy (N=107). MTHFR C677T polymorphism was analyzed using polymerase chain
      reaction followed by restriction fragment length polymorphism (PCR-RFLP) of
      genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using
      ARMS-PCR. RESULT: There was a significant difference in MTHFR polymorphism
      between the groups with and without neuropathy. CONCLUSION: Our results suggest
      that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients
      with type 2 diabetes.

PMID- 29222983
TI  - The action is in the task set, not in the action.
AB  - In 7 experiments we contrasted two accounts for novel sources of attentional
      bias. According to the action-based account, executing a motor response towards
      an object causes people to allocate attention preferentially towards properties
      of that object in a subsequent task even when properties of the acted-on object
      are task irrelevant. This remarkable view entails that motor processing is in
      itself sufficient to affect later attentional processing, in the absence of
      stimulus evaluation and motor preparation. In contrast, the attentional template
      matching account posits that observing an external object that matches one's
      prior attentional settings increases processing of that object even when
      properties of the item are no longer task relevant. Our findings indicate that
      when properties of a stimulus are task irrelevant, acting towards that object
      does not produce priming effects over and above what is observed from passive
      viewing of the object. Furthermore, when properties of the stimulus are task
      relevant, effects on attention are observed only when participants have
      sufficient information to generate a task based attentional template of the
      upcoming stimulus, regardless of whether they act towards the stimulus or not.
      Finally, effects on attention are found under conditions when participants are
      likely to experience an attentional template match but do not produce a response.
      Collectively, these results reveal that previously reported motor-based effects
      on attention instead reflect the effects of attentional bias towards objects that
      serve as prior targets. Our findings thus provide strong support for the
      attentional template view and no support for the action-based view.

PMID- 29222985
TI  - Absolute mRNA levels of inflammatory cytokines as treatment predictors in
      depression: Time for personalized medicine.

PMID- 29222984
TI  - Suicidal behaviour is associated with decreased esterified cholesterol in plasma
      and membrane fluidity of platelets.
AB  - BACKGROUND: Altered cholesterol levels in body fluids and brain tissues have been
      shown to be associated with suicidal behaviour, violence and aggression. But the
      biological underpinnings of this association in the pathophysiology of suicide
      are not clear. Cholesterol plays a crucial role in maintaining the cellular
      membrane fluidity and alterations in cellular membrane fluidity may impair
      serotonergic neurotransmission in the central nervous system. METHODS: We
      measured plasma esterified cholesterol and platelet membrane fluidity using
      fluorescence anisotropy and estimated flow activation energy which is a measure
      of order of membrane lipid bilayer in patients with recent suicidal attempt and
      compared with age and gender matched controls. RESULTS: The plasma esterified
      cholesterol, platelet membrane fluidity and flow activation energy was found to
      be significantly lower in patients with recent suicidal attempts compared to
      controls. CONCLUSION: Altered levels of plasma esterified cholesterol which is in
      equilibrium with membrane cholesterol might have resulted in decreased membrane
      fluidity and an increase in the order of membrane lipid bilayer. This might
      impair the serotonergic neurotransmission, which has been implicated in the
      pathophysiology of suicide.

PMID- 29222986
TI  - A case report of pregabalin use disorder with co-morbid somatic symptom disorder
      and depression.

PMID- 29222987
TI  - Frequency and correlates of tardive dyskinesia in Indian patients with type I
      bipolar disorder.
AB  - BACKGROUND: Patients with Bipolar Disorder (BD) may have higher risk of Tardive
      Dyskinesia (TD). Theories for TD include inflammatory or oxidative stress and
      altered iron metabolism. The current frequency and clinical and biochemical
      correlates of TD in BD needs exploration. OBJECTIVES: To assess: (1) the
      frequency of TD in BD; (2) clinical correlates of TD in BD; (3) oxidative stress
      markers, inflammatory markers and hepcidin in TD in BD. MATERIALS & METHODS: In
      this cross-sectional study, 170 patients with BD were assessed for clinical
      characteristics using structured assessments. Inflammatory and oxidative markers
      like Interleukin-6 (IL-6), high sensitivity C-Reactive Protein (hsCRP),
      malondialdehyde (MDA), Total Antioxidant Status (TAS) and hepcidin were assessed
      by ELISA. RESULTS: Frequency of TD was 10.6% (95%C.I.=6.4%-16.2%). Compared to
      patients without TD, patients with TD were older (F=0.340;p=0.000), had more
      episodes of illness (U=962.5;p=0.044) higher rates of medical comorbidity
      (X2=6.924; p=0.009*), antipsychotic exposure (U=592.5;p=0.000), typical
      antipsychotic exposure (U=756.5;p=0.001) and cognitive deficits
      (F=1.129;p=0.001). The biomarkers levels did not differ between the groups.
      Hepcidin levels correlated with Abnormal involuntary Movements scale (AIMS) score
      (r=0.213;p=0.006). Patients treated with lithium were more likely to have TD, but
      also had greater exposure to antipsychotics than patients on valproate.
      CONCLUSION: About one-tenth of patients with BD-I have TD. The presence of TD is
      associated several clinical characteristics such as age, exposure to typical
      antipsychotics and chronicity of illness. Hepcidin was associated with greater
      severity of dyskinetic movements and needs further exploration.

PMID- 29222988
TI  - Medically unexplained physical symptoms in patients attending a medical
      outpatient clinic in a tertiary hospital in North India.
AB  - OBJECTIVE: Medically unexplained physical symptoms (MUPS) are commonly seen
      across health care settings. Earlier studies have focussed on prevalence, cost
      utilization and burden. Data from India is scarce. Patients with persistent MUPS
      have more impairment and psychological distress. This study was designed to
      assess psychological morbidity, health anxiety (HA), somatic symptom load,
      disability, quality of life (QOL) in patients with persistent MUPS presenting to
      a general medical outpatient service and compare it with patients with medically
      explained physical symptoms (MEPS). METHODS: The study was conducted in the
      outpatient service of the Department of Internal Medicine in a tertiary hospital
      in North India. Persistent MUPS was defined as physical symptoms of at least 3
      months duration leading to dysfunction and with no identifiable medical cause. 70
      patients with persistent MUPS and MEPS each were recruited. Psychiatric morbidity
      was assessed using the Mini International Neuropsychiatric interview, somatic
      symptom load with Patient Health Questionniare-15 (PHQ-15), HA with Whiteley
      Index, disability with WHODAS 2.0 and QOL with WHOQOL-Bref. RESULTS: Both the
      groups were comparable on socio-demography and length of symptoms. Prevalence of
      psychiatric disorders and HA was significantly greater in MUPS. Patients with
      persistent MUPS had significantly more health care utilization, number and burden
      of somatic symptoms, greater disability and worse QOL. CONCLUSIONS: Patients with
      persistent MUPS have a different profile when compared to MEPS. There is a need
      to screen and identify patients with MUPS and manage them keeping in mind the
      psychological factors and chronic nature and number of symptoms.

PMID- 29222989
TI  - Disrupted circuits in mouse models of autism spectrum disorder and intellectual
      disability.
AB  - Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a
      wide range of genetic mutations, a significant fraction of which reside in genes
      important for synaptic function. Studies have found that sensory, prefrontal,
      hippocampal, cerebellar, and striatal regions, as well as the circuits that
      connect them, are perturbed in mouse models of ASD and ID. Dissecting the
      disruptions in morphology and activity in these neural circuits might help us to
      understand the shared risk between the two disorders as well as their clinical
      heterogeneity. Treatments that target the balance between excitation and
      inhibition in these regions are able to reverse pathological phenotypes,
      elucidating this deficit as a commonality across models and opening new avenues
      for intervention.

PMID- 29222990
TI  - Rapid and irreversible sorption behavior of 7Be assessed to evaluate its use as a
      catchment sediment tracer.
AB  - Beryllium-7 (7Be) has been used as a sediment tracer to evaluate soil
      redistribution rates at hillslopes and as a tool to estimate sediment residence
      time in river systems. A key assumption for the use of 7Be as a sediment tracer
      is the rapid and irreversible sorption of 7Be upon contact with the soil
      particles. However, recent studies have raised questions about the validity of
      these assumptions. Seven soil types were selected to assess the adsorption rate
      of 7Be on the soil particles, subsequently an extraction experiment was performed
      to assess the rate of desorption. Next, different treatments were applied to
      assess the impact of soil pH, fertilizer, humic acid and organic matter on the
      adsorption of Be. Finally, the influence of regularly occurring cations present
      on the soil complex on the adsorption of Be on pure clay minerals was evaluated.
      The adsorption rate experiment showed a rapid and nearly complete sorption of Be
      for Luvisols and Cambisols under agriculture. For a temperate climate Stagnosol
      under forest and two highly weathered tropical Ferralsols sorption of Be was less
      rapid and less complete. This may result in an incomplete adsorption of 7Be on
      these three soils when runoff initiates, which could lead to an overestimation of
      erosion rates and sediment residence time. Additional observations were made
      during the extraction experiment, showing a significant loss of Be from the
      forest Stagnosol and a stable binding of Be to the arable soils. Of the different
      treatments applied, only pH showed to be of influence. Finally, Ca2+ and NH4+ on
      the soil complex had only a limited effect on the adsorption of Be, while Al3+ in
      combination with a low pH inhibits the adsorption of Be on the exchange complex
      of the pure clay minerals. All these findings more rigorously support the use of
      7Be as a soil redistribution tracer in arable soils in a temperate climate at a
      hillslope scale. The use of 7Be in highly weathered Ferralsols or forest rich
      environments should be limited to avoid overestimations of erosion rates. The
      spatially extended use of 7Be to evaluate residence times of sediments should be
      avoided in catchments with rapid changing environmental parameters as they might
      influence the sorption behavior of 7Be.

PMID- 29222991
TI  - Salivary immune proteins monitoring can help detection of binge and chronic
      alcohol drinkers: Preliminary findings.
AB  - BACKGROUND: We compared effects of binge and chronic alcohol drinking on oral
      health and salivary immunity proteins. METHODS: The study involved males: 13
      healthy social-drinking (C), 10 alcohol-dependent after chronic alcohol
      intoxication (A), and 8 binge-drinkers after a single binge-drinking session (B).
      We compared periodontal/dental state and salivary immune proteins (lactoferrin 
      Lf, lysozyme -Lz, oral peroxidase -OPO, immunoglobulin A -IgA) in all groups.
      RESULTS: Group A had worse dental and periodontal states than group C and B.
      Group B had a lower OPO activity and Lz concentration, and a higher IgA
      concentration in comparison to group C. Group A had a higher OPO activity than
      group C. Group B had a lower Lz and a higher LF and IgA outputs than C. Group A
      had a lower IgA output and a strong tendency of Lf and Lz outputs to be lower
      than in group C. Positive correlations were found between alcohol amounts and OPO
      and Lf output in group A, with no such correlations in group B. Only IgA
      concentration in group B and OPO activity in group A have potential to be markers
      that help to differentiate binge from chronic alcohol drinking, and OPO activity
      had better accuracy than IgA. CONCLUSION: Binge alcohol consumption resulted in
      specific disturbances in salivary innate immunity (Lz), whereas chronic drinking
      led to disturbances in both adaptive and innate immunity (IgA, Lz and Lf). There
      is potential applicability of raised salivary IgA concentration and especially
      OPO activity in binge and chronic drinking detection and differential-diagnosis.

PMID- 29222992
TI  - Inflammatory chemokine eotaxin-1 is correlated with age in heroin dependent
      patients under methadone maintenance therapy.
AB  - BACKGROUND: Degeneration of central neurons and fibers has been observed in
      postmortem brains of heroin dependent patients. However, there are no biomarkers
      to predict the severity of neurodegeneration related to heroin dependence. A
      correlation has been reported between inflammatory C-C motif chemokine ligand 11
      (CCL11, or eotaxin-1) and neurodegeneration in Alzheimer's disease. METHODS:
      Three-hundred-forty-four heroin dependent, Taiwanese patients under methadone
      maintenance treatment (MMT) were included with clinical assessment and genomics
      information. Eighty-seven normal control subjects were also recruited for
      comparison. RESULTS: Using receiver operating characteristics curve analyses,
      CCL11 showed the strongest sensitivity and specificity in correlation with age by
      a cut-off at 45 years (AUC = 0.69, P < 0.0001) in MMT patients, but not normal
      controls. Patients 45 years of age or older had significantly higher plasma
      levels of CCL11, fibroblast growth factor 2 (FGF-2), nicotine metabolite
      cotinine, and a longer duration of addiction. Plasma level of CCL11 was
      correlated with that of FGF-2 (partial r2 = 0.24, P < 0.0001). Carriers with the
      mutant allele of rs1129844, a functional single nucleotide polymorphism
      (Ala23Thr) in the CCL11 gene, showed a higher plasma level of Abeta42, ratio of
      Abeta42/Abeta40, and insomnia side effect symptom score than the GG genotype
      carriers among MMT responders with morphine-negative urine results. CONCLUSIONS:
      The results suggest possible novel mechanisms mediated through CCL11 involving
      neurotoxicity in heroin dependent patients.

PMID- 29222993
TI  - Supplementation of gamma-aminobutyric acid (GABA) affects temporal, but not
      spatial visual attention.
AB  - In a randomized, double-blind, and placebo-controlled experiment, the acute
      effects of gamma-aminobutyric acid (GABA) supplementation on temporal and spatial
      attention in young healthy adults were investigated. A hybrid two-target rapid
      serial visual presentation task was used to measure temporal attention and
      integration. Additionally, a visual search task was used to measure the speed and
      accuracy of spatial attention. While temporal attention depends primarily on the
      distribution of limited attentional resources across time, spatial attention
      represents the engagement and disengagement by relevant and irrelevant stimuli
      across the visual field. Although spatial attention was unaffected by GABA
      supplementation altogether, we found evidence supporting improved performance in
      the temporal attention task. The attentional blink was numerically, albeit not
      significantly, attenuated at Lag 3, and significantly fewer order errors were
      committed at Lag 1, compared to the placebo condition. No effect was found on
      temporal integration rates. Although there is controversy about whether oral GABA
      can cross the blood-brain barrier, our results offer preliminary evidence that
      GABA intake might help to distribute limited attentional resources more
      efficiently, and can specifically improve the identification and ordering of
      visual events that occur in close temporal succession.

PMID- 29222994
TI  - Supportive environments for physical activity in deprived communities in the
      United Kingdom: A qualitative study using photo elicitation.
AB  - The health benefits of regular physical activity are substantial and well
      established. However, population activity levels are insufficient to obtain
      health benefits in the United Kingdom (UK), and strategies to increase activity,
      particularly in income-deprived communities, are sought. Socioecological models
      of physical activity posit that activity levels are influenced by social,
      physical and wider environmental factors. In line with a growing evidence base,
      there is a need to understand the factors that contribute to an activity
      supportive neighbourhood within deprived settings within the UK. This study used
      photo-elicitation qualitative interviews to explore environmental facilitators
      and barriers to neighbourhood-based, outdoor physical activity in 23 adults
      living in two income-deprived neighbourhoods in Glasgow, UK. Data were collected
      between June and October 2015, and were explored using thematic analysis. Five
      themes were identified: 'diversity of destinations in the neighbourhood',
      'provision of services to support healthy environments', 'ownership of public
      space and facilities to encourage physical activity', 'collective control of
      public space to prevent disorder' and 'perceived value of the neighbourhood'.
      Findings highlighted the close interaction between these themes and more broadly
      between social and physical facets of neighbourhood environments that were
      unsupportive of physical activity. Discourse about economic aspects was pervasive
      and emerged as deeply affecting characteristics of the social and physical
      environment and upstream influences on physical activity. This study supports
      evidence that multi-faceted interventions addressing aspects of the social,
      physical and economic environment may be needed to support outdoor physical
      activity in deprived communities.

PMID- 29222995
TI  - Updating Edwin Chadwick's seminal work on geographical inequalities by
      occupation.
AB  - To honour the 175th anniversary of Edwin Chadwick's seminal 'Report on the
      Sanitary Conditions of the Labouring Poor', we update Chadwick's famous analysis
      of geographical differences in occupational based inequalities. Much of the field
      of Health Geography owes both its direction of development and its initial
      impetus to his 1842 report. The report presented evidence for the importance of
      local context to health, with individuals of the lowest occupations in Rutland
      living longer than individuals of the highest occupations in Liverpool. Here we
      update the 1842 analysis using data from the Office of National Statistics on
      individual mortality records by occupation (2010-12) and population data from the
      2011 Census. Sex-specific directly standardised premature (16-74) mortality rates
      were calculated for hierarchical occupational categories similar to Chadwick's
      categories, for the nearest equivalent areas to those used in Chadwick's report.
      Although there is no longer consistent evidence on individuals in the lowest
      occupational group having lower mortality rates than those in the highest group,
      there were clear social gradients in mortality within each area and the extent of
      these inequalities varied between areas. Individuals who live in Rutland had
      lower premature mortality rates across each occupational group compared to the
      other areas. Our results demonstrate that while life expectancy has nearly
      doubled since Chadwick's report, social and spatial inequalities in health have
      persisted. We suggest that Chadwick's legacy on the importance of locality
      continues.

PMID- 29222996
TI  - The consequence of "doing nothing": Family caregiving for Alzheimer's disease as
      non-action in the US.
AB  - This article adopts a discursive approach in order to examine how dominant US
      discourses shape both public and personal understandings of the caregiving work
      that families do, specifically in the context of Alzheimer's disease (AD). Family
      caregivers are an essential, increasingly recognized piece of the US health care
      system. Dominant discourses of AD and caregiving articulate family caregiving in
      contrast to biomedical intervention. The dichotomy privileges the ability to
      affect a biomedical outcome and, using that metric, minimizes caregiving's
      potential value as meaningful action. Family caregiving comes to be seen as what
      I term non-action, action that, while voluminous, is not perceived as meaningful
      in terms of its outcome. Drawing on over 26 months of ethnographic fieldwork in
      the Midwestern US with families living with early-onset AD (2011-2013), I focus
      on spousal caregivers to trace how these discourses shape the possibilities for
      family caregiving. I show how advocacy rhetoric is taken up and reproduced by
      family members, who learn to see their own caregiving labor through a biomedical
      lens. However, I also demonstrate that, obscured by dominant discourses,
      caregivers engage in relational labor, the continual work of making and unmaking
      social relations. Recognition of caregiving as part of longer-term relational
      endeavors, I argue, offers the potential to reframe caregiving discourses and
      reimagine the value the labor of caregiving as meaningful in its own right.

PMID- 29222997
TI  - "That wasn't really a place to worry about diabetes": Housing access and diabetes
      self-management among low-income adults.
AB  - Lack of affordable housing access represents a significant and growing problem
      for low-income households in the United States and these housing challenges may
      present barriers to the management of chronic diseases such as type 2 diabetes.
      In this qualitative study, we examined how both housing challenges and housing
      resources shaped diabetes self-management behaviors. We conducted semi-structured
      interviews with 40 low-income residents of one US city, New Haven, Connecticut,
      who had a diagnosis of type 2 diabetes and either resided in or qualified for
      subsidized housing. We purposively constructed our sample to include a range of
      housing experiences (subsidized, unsubsidized, homeless) and treatment regimes.
      We analyzed the data using grounded theory techniques of inductive coding and
      memo writing. Our findings suggest multiple ways that housing access can affect
      diabetes self-management with implications for blood glucose levels and future
      complications. Specifically, we describe the ways that housing access affected
      participants' ability to: 1) prioritize their diabetes care, 2) establish and
      maintain diabetes routines, and 3) afford diabetes-related expenses. Together,
      our findings show how housing challenges increased the cost of adherence to
      diabetes management regimes such that inadequately housed individuals had to both
      invest and sacrifice more for the same outcomes. Our findings suggest that
      improved affordable housing access may represent an opportunity to improve
      outcomes and reduce socioeconomic disparities among those living with type 2
      diabetes.

PMID- 29222998
TI  - Experiences of connectivity and severance in the wake of a new motorway:
      Implications for health and well-being.
AB  - The construction of new urban roads may cause severance, or the separation of
      residents from local amenities or social networks. Using qualitative data from a
      natural experimental study, we examined severance related to a new section of
      urban motorway constructed through largely deprived residential neighbourhoods in
      Glasgow, Scotland. Semi-structured and photo-elicitation interviews were used to
      better understand severance and connectivity related to the new motorway, and
      specifically implications for individual and community-level health and well
      being through active travel and social connections. Rather than a clear severance
      impact attributable to the motorway, a complex system of connection and severance
      was spoken about by participants, with the motorway being described by turns as a
      force for both connection and severance. We conclude that new transport
      infrastructure is complex, embedded, and plausibly causally related to
      connectedness and health. Our findings suggest the potential for a novel
      mechanism through which severance is enacted: the disruptive impacts that a new
      road may have on third places of social connection locally, even when it does not
      physically sever them. This supports social theories that urge a move away from
      conceptualising social connectedness in terms of the local neighbourhood only,
      towards an understanding of how we live and engage dynamically with services and
      people in a much wider geographical area, and may have implications for local
      active travel and health through changes in social connectedness.

PMID- 29222999
TI  - The symbolic affordances of a video-mediated gaze in emergency psychiatry.
AB  - While mental illness is a significant health challenge worldwide, the
      availability of specialists is limited, especially in rural areas and for
      psychiatric emergencies. Although tele-psychiatry, via real-time
      videoconferencing (VC), is used to provide consultative services in areas that
      lack psychiatrists, there are a paucity of studies on the use of VC for
      psychiatric emergencies. We examine how VC matters for patient involvement and
      professional practice in the first Norwegian emergency tele-psychiatric service.
      Through a decentralised on-call system, psychiatrists are accessible 24/7 by
      telephone and VC for patients and nurses in regional psychiatry centres. Based on
      29 interviews with patients, psychiatrists and nurses, this article addresses how
      participation is fostered by VC, and how it may change the social dynamics of
      therapeutic emergency encounters. We identified four contributions of the 'video
      mediated gaze' in the therapeutic encounter including those of the: (1) immediacy
      of assessment, (2) increased transparency, (3) sense of access to the 'real'
      expert, and (4) fostering of the patient's 'voice' in therapeutic decisions.
      These VC inflections of the therapeutic encounter are a mix of the pragmatic (1
      and 2) and the symbolic (3 and 4), assembling in these contexts to foster patient
      centeredness. With a sociological approach to video-conferenced emergency
      psychiatry, the identification of symbolic affordances adds necessary nuances to
      the application of new technologies into fragile therapeutic communication.

PMID- 29223000
TI  - Bilateral preictal signature of phase-amplitude coupling in canine epilepsy.
AB  - Seizure forecasting would improve the quality of life of patients with refractory
      epilepsy. Although early findings were optimistic, no single feature has been
      found capable of individually characterizing brain dynamics during transition to
      seizure. Cross-frequency phase amplitude coupling has been recently proposed as a
      precursor of seizure activity. This work evaluates the existence of a
      statistically significant difference in mean phase amplitude coupling
      distribution between the preictal and interictal states of seizures in dogs with
      bilaterally implanted intracranial electrodes. Results show a statistically
      significant change (p<0.05) of phase amplitude coupling during the preictal
      phase. This change is correlated with the position of implanted electrodes and is
      more significant within high-gamma frequency bands. These findings highlight the
      potential benefit of bilateral iEEG analysis and the feasibility of seizure
      forecasting based on slow modulation of high frequency amplitude.

PMID- 29223001
TI  - A content analysis of thinspiration images and text posts on Tumblr.
AB  - Thinspiration is content advocating extreme weight loss by means of images and/or
      text posts. While past content analyses have examined thinspiration content on
      social media and other websites, no research to date has examined thinspiration
      content on Tumblr. Over the course of a week, 222 images and text posts were
      collected after entering the keyword 'thinspiration' into the Tumblr search bar.
      These images were then rated on a variety of characteristics. The majority of
      thinspiration images included a thin woman adhering to culturally based beauty,
      often posing in a manner that accentuated her thinness or sexuality. The most
      common themes for thinspiration text posts included dieting/restraint, weight
      loss, food guilt, and body guilt. The thinspiration content on Tumblr appears to
      be consistent with that on other mediums. Future research should utilize
      experimental methods to examine the potential effects of consuming thinspiration
      content on Tumblr.

PMID- 29223003
TI  - Steroidogenic factor-1 inverse agonists as a treatment option for canine
      hypercortisolism: in vitro study.
AB  - Hypercortisolism is one of the most commonly diagnosed endocrinopathies in dogs,
      and new targeted medical treatment options are desirable. Steroidogenic factor-1
      (SF-1), an orphan nuclear hormone receptor, is a key regulator of adrenal
      steroidogenesis, development, and growth. In pituitary-dependent hypercortisolism
      (PDH), high plasma ACTH concentrations increase the transcriptional activity of
      SF-1. In adrenal-dependent hypercortisolism, SF-1 expression is significantly
      greater in dogs with recurrence after adrenalectomy than in those without
      recurrence. Inhibition of SF-1 could therefore be an interesting treatment option
      in canine spontaneous hypercortisolism. We determined the effects of 3 SF-1
      inverse agonists, compounds IsoQ A, #31, and #32, on cortisol production, on the
      messenger RNA (mRNA) expression of steroidogenic enzymes and SFs, and on cell
      viability, in primary adrenocortical cell cultures of 8 normal adrenal glands and
      of 3 cortisol-secreting adrenocortical tumors (ATs). To mimic PDH, the normal
      adrenocortical cell cultures were stimulated with ACTH. The results show that
      only compound #31 inhibited cortisol production and SF-1 target gene expression
      in non-ACTH-stimulated and ACTH-stimulated normal adrenocortical cells but did
      not affect cell viability. In the AT cell cultures, the effects of #31 on
      cortisol production and target gene expression were variable, possibly caused by
      a difference in the SF-1 mRNA expressions of the primary tumors. In conclusion,
      inhibition of SF-1 activity shows much promise as a future treatment for canine
      hypercortisolism.

PMID- 29223002
TI  - Basal and reactivity levels of cortisol in one-month-old infants born to
      overweight or obese mothers from an ethnically and racially diverse, low-income
      community sample.
AB  - Establishing typical values of the steroid hormone cortisol at rest and after
      challenge is critical for understanding how environmental factors impact stress
      regulation and overall development, beginning at birth. Yet most extant samples
      are small or based upon low-risk populations, and few studies address the
      potential role of maternal weight during pregnancy in their study designs or
      sampling strategy. Here we report basal and reactivity levels of salivary
      cortisol within a racially and ethnically diverse sample of 132 infants
      approximately one month of age (Age in days: M=37.61, SD=7.27) born to lower
      income overweight or obese mothers. Reactivity was assessed in response to a
      multi-domain infant stressor paradigm, which included assessment via the Newborn
      Behavioral Observation (NBO) system and extensive anthropometric measurements.
      Sample means for basal, post stressors, and reactivity to the NBO were
      significantly lower than those reported in reviews of low-risk samples. Parity
      was associated with cortisol levels such that first-born infants had lower
      resting cortisol and higher reactivity than infants born to multiparous women.
      Latino infants had lower basal cortisol. No other demographic characteristics
      significantly predicted cortisol. The variability in cortisol levels present in
      this sample suggests that considerable psychophysiological diversity may exist in
      samples of low-SES or high-risk participants. Findings provide useful ranges for
      samples of racially and ethnically diverse newborns from low-income families.

PMID- 29223004
TI  - Towards utilization of the human genome and microbiome for personalized
      nutrition.
AB  - Generalized dietary and lifestyle guidelines have been formulated and published
      for decades now from a variety of relevant agencies in an attempt to guide people
      towards healthy choices. As the pandemic rise in metabolic diseases continues to
      increase, it has become clear that the one-fit-for-all diet approach does not
      work and that there is a significant variation in inter-individual responses to
      diet and lifestyle interventions. Recent technological advances have given an
      unprecedented insight into the sources of this variation, pointing towards our
      genome and microbiome as potentially and previously under-explored culprits
      contributing to individually unique dietary responses. Variations in our genome
      influence the bioavailability and metabolism of nutrients between individuals,
      while inter-individual compositional variation of commensal gut microbiota leads
      to different microbe functional potential, metabolite production and metabolism
      modulation. Quantifying and incorporating these factors into a comprehensive
      personalized nutrition approach may enable practitioners to rationally
      incorporate individual nutritional recommendations in combating the metabolic
      syndrome pandemic.

PMID- 29223005
TI  - The emerging role of systems biology for engineering protein production in CHO
      cells.
AB  - To meet the ever-growing demand for effective, safe, and affordable protein
      therapeutics, decades of intense efforts have aimed to maximize the quantity and
      quality of recombinant proteins produced in CHO cells. Bioprocessing innovations
      and cell engineering efforts have improved product titer; however,
      uncharacterized cellular processes and gene regulatory mechanisms still hinder
      cell growth, specific productivity, and protein quality. Herein, we summarize
      recent advances in systems biology and data-driven approaches aiming to unravel
      how molecular pathways, cellular processes, and extrinsic factors (e.g. media
      supplementation) influence recombinant protein production. In particular, as the
      available omics data for CHO cells continue to grow, predictive models and
      screens will be increasingly used to unravel the biological drivers of protein
      production, which can be used with emerging genome editing technologies to
      rationally engineer cells to further control the quantity, quality and
      affordability of many biologic drugs.

PMID- 29223007
TI  - Examining health service utilization, hospital treatment cost, and mortality of
      individuals with epilepsy and status epilepticus in New South Wales, Australia
      2012-2016.
AB  - This study examined the health service utilization and hospital treatment cost of
      individuals with epilepsy by age group, mortality within 30days, and surgical
      outcomes for individuals with refractory epilepsy in New South Wales (NSW),
      Australia. A retrospective examination of linked hospitalization and mortality
      data for individuals hospitalized with a diagnosis of epilepsy during 2012-2016.
      Hospitalized incidence rates per 1000 population were calculated, and negative
      binomial regression was used to examine temporal trends. Mortality within 30days
      of hospitalization was identified, along with cause of death. There were 44,722
      hospitalizations during the five-year period, with a hospitalization rate of 85.6
      per 1000 population (95% confidence interval (CI): 84.7-86.4). Total hospital
      treatment costs were AUD$402.9 million. Children aged <=17years accounted for
      32.0% of hospitalizations. Just over half to two-thirds of hospitalizations for
      each age group were for a principal diagnosis of epilepsy, with 2976
      hospitalizations of individuals for status epilepticus. The overall mean hospital
      length of stay (LOS) for epilepsy hospitalizations was 5.1days (standard
      deviation (SD)=9.0). Thirty-day mortality was highest for individuals aged
      >=65years (6.7%), and epilepsy was identified as the underlying cause of death
      for 18.2% of deaths. This research has provided insight into the healthcare
      utilization profiles of individuals with epilepsy at different ages. Epilepsy
      hospitalizations constitute a substantial cost to the healthcare system, and
      better overall management of seizures and comorbid conditions is likely to lead
      to a reduction in the need for hospitalization.

PMID- 29223006
TI  - The Temple Star Transitional Model of Care for epilepsy; the outcome of a quality
      improvement project.
AB  - OBJECTIVE: The aim and objective of this study was to assess the knowledge and
      views of parents on transitional and adolescent care in young adults with
      epilepsy, and to develop a transitional and adolescent program for epilepsy.
      METHODS: Data were collected from questionnaires completed by parents during
      focus groups exploring transitional care and inherent issues for young adults,
      aged 12-18years, with epilepsy. The questionnaire assessed the current knowledge
      and views of parents of children with epilepsy on transitional care, and
      following a presentation on "Transition in Epilepsy" (including themes such as
      self-advocacy, independent healthcare behavior, sexual health, psychosocial
      support, educational and vocational planning, health and lifestyle issues)
      assessed feedback on the proposed model of care in transitional and adolescent
      care. RESULTS: Data were collected from 34 parents; the majority of parents, 74%
      (n=25), wish their children to be transitioned and transferred over to the adult
      epilepsy sites at the age of 18years. Over 82% (n=28) of parents believe the
      concept of transition should be introduced between the ages of 12-16years.
      CONCLUSION: This quality improvement initiative identified the need for
      transitional care to begin at an early age. This study engaged parents in a
      process to improve adolescent and transitional care for adolescents with
      epilepsy. This study also highlights the importance of introducing a detailed
      preparatory phase for a transitional and adolescent care in epilepsy.

PMID- 29223008
TI  - Single molecule force spectroscopy: a new tool for bioinorganic chemistry.
AB  - Metalloproteins are essential in biology. The incorporation of metal ion into
      metalloproteins significantly expands protein functionality and enhances protein
      stability. Over the last few years, atomic force microscopy-based single molecule
      force spectroscopy (SMFS) has evolved into a unique tool allowing for probing
      metalloproteins and metalligand bonds one molecule/bond at a time. Mechanical
      strength of a wide variety of metalligand bonds has been measured in metal-ligand
      complexes as well as in metalloproteins, providing detailed information of their
      underlying free energy profiles and the influence of the protein environment on
      the bond strength. SMFS experiments have directly demonstrated the effect of the
      metal binding on the mechanical stability of proteins. Moreover, SMFS has enabled
      the direct observation of the unfolding and folding of metalloproteins, revealing
      detailed mechanistic insight into the unfolding pathways modulated by the metal
      center.

PMID- 29223009
TI  - Influence of spermatozoal lipidomic profile on the cryoresistance of frozen
      spermatozoa from stallions.
AB  - The membrane of spermatozoa, which contributes to cellular cryoresistance,
      contains numerous lipids with a composition that directly affects membrane
      fluidity and the fertilization process. In light of variations in the degree of
      sensitivity in equine seminal freezing, this study aimed to correlate equine
      semen lipids with post-thawing characteristics of spermatozoa. We used ejaculates
      from 34 stallions, which were evaluated (total motility >= 60%), frozen and
      thawed and reevaluated for motility of spermatozoa, membrane integrity and lipid
      peroxidation. Lipid extraction of the fresh semen samples was performed by liquid
      liquid extraction, and fingerprinting lipid analysis was conducted by matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS). Based on the
      characteristics of spermatozoa after thawing, the animals could be separated into
      two groups: resistant (Good Freezers, n = 5) and sensitive (Bad Freezers, n = 6)
      to freezing, and their MALDI-MS data were then compared. The Good Freezers group
      showed a higher abundance of phosphatidylcholines (m/z 796.6, 846.6, 810.6, 854.6
      and 732.6). The ions of m/z 812.6, 832.6, 836.6 and 838.6 belonging to the
      phosphatidylcholine lipid class were also positively correlated with motility of
      spermatozoa, whereas that of m/z 794.6 was negatively correlated with lipid
      peroxidation in thawed semen. The Bad Freezer group, displayed higher abundance
      of one phosphatidylcholines (m/z 806.6), as well as a sphingomyelins (m/z 703.5),
      which were negatively correlated (univariate analysis) with kinetics of
      spermatozoa after thawing (m/z 703.5) and with membrane integrity (m/z 792.6).
      The ion of m/z 717.5, assigned to phosphatidic acid, was negatively correlated
      with lipid peroxidation. In general therefore, the phosphatidylcholines are
      associated with higher quality of spermatozoa after thawing, especially in
      functional capacity, and that lipid semen composition was found to influence the
      resistance of spermatozoa to cryopreservation and may interfere with motility,
      membrane integrity and lipid peroxidation in stallions.

PMID- 29223010
TI  - Pelvic abscess complicating sigmoid colon perforation by migrating intrauterine
      device: A case report and review of the literature.
AB  - INTRODUCTION: Intrauterine devices (IUDs) are commonly used as a contraceptive
      method. However, they may cause rare but potentially serious complications such
      as migration through the uterine wall and gastrointestinal perforation.
      PRESENTATION OF CASE: We report a case of a 26-year woman, carrying an IUD for 2
      years, who presented to the emergency with pelvic pain with breakthrough
      bleeding. Abdominal imaging revealed the presence of two devices the first of
      which was located in the uterine cavity and the other in the wall of the sigmoid
      colon associated with a 5-centimeter pelvic collection. Intraoperatively, the IUD
      was found to be embedded in the wall of the sigmoid colon which was removed by
      wedge resection of the involved segment followed by a closure of the puncture
      with drainage. DISCUSSION: The Intrauterine Device (IUD) is an effective method
      of contraception, relatively well tolerated, reversible, inexpensive and widely
      used. However, it is not without risk. Indeed, serious complications can occur
      such as uterine perforation and migration to adjacent abdomino-pelvic structures.
      Our observation illustrates its rarity given the fact that this complication has
      been observed the first time in our department over the last ten years.
      CONCLUSION: The migration of IUD must be treated even in asymptomatic patients
      due to the risk of severe complications.

PMID- 29223011
TI  - Veno-venous ECMO during surgical repair of tracheal perforation: A case report.
AB  - INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is used extensively in
      cardiothoracic surgery both for hemodynamic and respiratory support. It has
      proven to be a valuable tool to maintain adequate oxygenation during tracheal
      surgery. Airway lesion may be an indication for veno-venous ECMO both in case of
      conservative management and in case of surgical repair. Here we report the case
      of a patient with a iatrogenic tracheal injury, successfully operated with the
      support of veno-venous extracorporeal oxygenation. PRESENTATION OF CASE: A 39
      year-old female underwent an elective laparoscopic adhesiolysis. At the end of
      the procedure, the patient had developed subcutaneous emphysema. A CT-scan showed
      mediastinal and subcutaneous emphysema and left pneumothorax with a laceration of
      the membranous portion of the middle third of the trachea. A left pleural drain
      was inserted and a bronchoscopy showed a 2-cm long tear of the membranous portion
      in the middle third of the trachea. Veno-venous ECMO was established and surgical
      repair of the tracheal lesion was performed. Post-operative recovery was
      uneventful and the patient was discharged on 8th postoperative day. DISCUSSION:
      The use of Veno-venous ECMO allowed a safe intubation with optimal oxygenation. A
      selective intubation with a small tube was performed to prevent further tracheal
      injury and allow an adequate surgical space for tracheal repair. CONCLUSION: The
      use of ECMO support represents a safe and effective way to manage patients with
      ITI when surgical repair with minimally invasive ventilation is needed. Since
      this is a case report larger studies are needed to validate the technique.

PMID- 29223012
TI  - Support vector machine with Dirichlet feature mapping.
AB  - The Support Vector Machine (SVM) is a supervised learning algorithm to analyze
      data and recognize patterns. The standard SVM suffers from some limitations in
      nonlinear classification problems. To tackle these limitations, the nonlinear
      form of the SVM poses a modified machine based on the kernel functions or other
      nonlinear feature mappings obviating the mentioned imperfection. However,
      choosing an efficient kernel or feature mapping function is strongly dependent on
      data structure. Thus, a flexible feature mapping can be confidently applied in
      different types of data structures without challenging a kernel selection and its
      tuning. This paper introduces a new flexible feature mapping approach based on
      the Dirichlet distribution in order to develop an efficient SVM for nonlinear
      data structures. To determine the parameters of the Dirichlet mapping, a tuning
      technique is employed based on the maximum likelihood estimation and Newton's
      optimization method. The numerical results illustrate the superiority of the
      proposed machine in terms of the accuracy and relative error rate measures in
      comparison to the traditional ones.

PMID- 29223013
TI  - Effectiveness of flipped classrooms in Chinese baccalaureate nursing education: A
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: In recent years, the flipped classroom approach has been broadly
      applied to nursing courses in China. However, a systematic and quantitative
      assessment of the outcomes of this approach has not been conducted. OBJECTIVE:
      The purpose of the meta-analysis is to evaluate the effectiveness of the flipped
      classroom pedagogy in Chinese baccalaureate nursing education. DESIGN: Meta
      analysis of randomized controlled studies. DATA SOURCE: All randomized controlled
      trials relevant to the use of flipped classrooms in Chinese nursing education
      were retrieved from the following databases from their date of inception through
      September 23, 2017: PubMed, EMBASE, the Cochrane Central Register of Controlled
      Trials, CINAHL, the China National Knowledge Infrastructure, the Wanfang
      Database, and the Chinese Scientific Journals Database. Search terms including
      "flipp*", "inverted", "classroom", and "nurs*" were used to identify potential
      studies. We also manually searched the reference lists of the retrieved articles
      to identify potentially relevant studies. REVIEW METHODS: Two reviewers
      independently assessed the eligibility of each study and extracted the data. The
      Cochrane risk-of-bias tool was used to evaluate the quality of the studies.
      RevMan (Version 5.3) was used to analyze the data. Theoretical knowledge scores
      and skill scores (continuous data) were synthesized using the standardized mean
      difference (SMD) and 95% confidence interval (CI). The statistical heterogeneity
      of the included studies was analyzed by calculating the I2 statistic and applying
      a chi-square test. Publication bias was assessed by funnel plots. The quality of
      the combined results was evaluated using the Grading of Recommendations
      Assessment, Development and Evaluation system. RESULTS: Eleven randomized
      controlled trials published between 2015 and 2017 were selected. All the included
      studies had a moderate possibility of bias due to low methodological quality. The
      meta-analysis indicated that the theoretical knowledge scores and skill scores
      were significantly higher in the flipped classroom group than in the traditional
      lectures group (SMD=1.06, 95% CI: 0.70-1.41, P <0.001, and SMD=1.40, 95% CI: 0.46
      2.34, P <0.001). There was no significant publication bias indicated in the
      primary analysis. Sensitivity analysis showed that the results of our meta
      analysis were reliable. The evidence grades of the results regarding the
      theoretical knowledge and skill scores were low and very low, respectively.
      CONCLUSION: Flipped classroom pedagogy is more effective than traditional
      lectures at improving students' theoretical knowledge and skill scores. Given the
      limitations of the included studies, more robust randomized controlled trials are
      warranted in a variety of educational settings to confirm our findings.

PMID- 29223014
TI  - Differentiation of dry-cured hams from different processing methods by means of
      volatile compounds, physico-chemical and sensory analysis.
AB  - The aim of this study was to characterize dry-cured hams from four different
      processing methods (differences in primary leg treatment, salting and smoking
      phase). Volatile compounds were isolated by using headspace-solid phase
      microextraction and analysed by gas chromatography/mass spectrometry (GC/MS).
      Samples were also evaluated by sensory and physico-chemical characteristics
      (moisture, protein, fat and NaCl content, aw, colour). 149 volatile compounds of
      dry-cured hams were identified and 15 of them were quantified. Identified
      volatile compounds belonged to several classes of chemical: 25 aldehydes, 18
      phenols, 12 alcohols, 16 terpenes, 27 aromatic hydrocarbons, 18 aliphatic
      hydrocarbons, 17 ketones, 9 esters and 7 acids. Most abundant volatiles in ham
      samples were aldehydes (34.46-49.78%). Principal component analysis showed a good
      separation among groups. Smoked dry-cured hams showed a higher content of
      phenols, aromatic hydrocarbons, and acids and were characterized by smoky aroma,
      while non-smoked dry-cured hams showed higher content of terpenes, ketones,
      alcohols, esters, aliphatic hydrocarbons and were characterized with spicy aroma.

PMID- 29223015
TI  - Thiamine accumulation and thiamine triphosphate decline occur in parallel with
      ATP exhaustion during postmortem aging of pork muscles.
AB  - We aimed to clarify the mechanisms affecting postmortem thiamine and its
      phosphoester contents in major edible pork muscles, namely the longissimus
      lumborum (LL) in addition to vastus intermedius (VI). Metabolomic analysis by
      capillary electrophoresis-time of flight mass spectrometry revealed that the
      level of thiamine triphosphate (ThTP), approximately 1.8-fold higher in LL than
      in VI muscle at 0h postmortem, declined in the first 24hrs, resulting in an
      undetectable level at 168h postmortem in both muscles. In contrast, the thiamine
      content in both muscles increased after 24h postmortem during the aging process.
      The thiamine accumulation and ThTP decline progressed in parallel with a drastic
      reduction of the ATP level. The intermuscular differences in pH at 24h and in
      expression of thiamine transporter and thiamine pyrophosphokinase might result in
      delayed thiamine generation in LL. These results suggest that postmortem ATP
      exhaustion forced ThTP hydrolysis and further depyrophosphorylation of thiamine
      diphosphate in the porcine muscles, which resulted in thiamine accumulation.

PMID- 29223016
TI  - Application of single nucleotide extension and MALDI-TOF mass spectrometry in
      proofreading and DNA repair assay.
AB  - Proofreading and DNA repair are important factors in maintaining the high
      fidelity of genetic information during DNA replication. Herein, we designed a non
      labeled and non-radio-isotopic simple method to measure proofreading. An
      oligonucleotide primer is annealed to a template DNA forming a mismatched site
      and is proofread by Klenow fragment of Escherichia coli DNA polymerase I (pol I)
      in the presence of all four dideoxyribonucleotide triphosphates. The proofreading
      excision products and re-synthesis products of single nucleotide extension are
      subjected to MALDI-TOF mass spectrometry (MS). The proofreading at the mismatched
      site is identified by the mass change of the primer. We examined proofreading of
      Klenow fragment with DNAs containing various base mismatches. Single mismatches
      at the primer terminus can be proofread efficiently. Internal single mismatches
      can also be proofread at different efficiencies, with the best correction for
      mismatches located 2-4-nucleotides from the primer terminus. For mismatches
      located 5-nucleotides from the primer terminus there was partial correction and
      extension. No significant proofreading was observed for mismatches located 6-9
      nucleotides from the primer terminus. We also subjected primers containing 3'
      penultimate deoxyinosine (dI) lesions, which mimic endonuclease V nicked repair
      intermediates, to pol I repair assay. The results showed that T-I was a better
      substrate than G-I and A-I, however C-I was refractory to repair. The high
      resolution of MS results clearly demonstrated that all the penultimate T-I, G-I
      and A-I substrates had been excised last 2 dI-containing nucleotides by pol I
      before adding a correct ddNMP, however, pol I proofreading exonuclease tolerated
      the penultimate C-I mismatch allowing the primer to be extended by polymerase
      activity.

PMID- 29223018
TI  - Targeting oxidant-dependent mechanisms for the treatment of respiratory diseases
      and their comorbidities.
AB  - Oxidative stress is implicated in the pathogenesis of respiratory diseases, such
      as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and
      radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear
      erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been
      developed to target oxidant-dependent mechanisms. The therapeutic effects of
      antioxidants have been generally disappointing. A small number of antioxidants
      are approved for clinical use, such as the small molecule thiol N-acetyl-l
      cysteine for chronic obstructive pulmonary disease, and in the United States, the
      superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis. The
      future use of antioxidants for the treatment of chronic respiratory diseases may
      require a precision medicine approach to identify responsive patients.

PMID- 29223017
TI  - Biceps femoris fascicle length during passive stretching.
AB  - The purpose of this study was to quantify the relative changes in fascicle (FL)
      and muscle-tendon unit (LMTU) length of the long head of the biceps femoris
      (BFlh) at different combinations of hip and knee joint positions. Fourteen
      participants performed passive knee extension trials from 0 degrees , 45 degrees 
      and 90 degrees  of hip flexion. FL, LMTU, pennation angle (PA) and effective FL
      (FL multiplied by the cosine of the PA) of the BFlh were quantified using
      ultrasonography (US). Three-way analysis of variance designs indicated that at
      each hip angle, FL and LMTU increased and PA decreased from 90 degrees  to 0
      degrees  of knee flexion. Increasing hip flexion angle from 0 degrees  to 90
      degrees  led to a higher FL and LMTU and a lower PA (p < .05). The average
      lengthening of the LMTU and effective FL was 28.00 +/- 1.82% and 85.88 +/-
      21.92%, respectively. The average effective FL change accounted for 51.36 +/-
      7.39% of LMTU change. The relationship between effective FL and LMTU was almost
      linear with a slope equal to 0.49 +/- 0.06 (r2 = 0.52 to 0.97). To achieve
      greater lengthening of the fascicles of the BFlh, passive stretch with the hip
      flexed at least 45 degrees  and the knee reaching full extension is necessary.

PMID- 29223019
TI  - Are pathological high-risk features in locally advanced rectal cancer a useful
      selection tool for adjuvant chemotherapy?
AB  - BACKGROUND: Several histological high-risk factors are used as an indication for
      adjuvant therapy in stage II colon cancer. Those and other factors, including
      lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding
      are associated with decreased outcome. In this study, we evaluated the prognostic
      and predictive values of these biomarkers in a cohort of rectal cancer patients.
      MATERIALS AND METHODS: The trial-based cohort consisted of 221npTNM stage II-III
      rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre
      randomised phase III trial. Patients treated with neoadjuvant radiotherapy and
      TME surgery were randomised between adjuvant chemotherapy or observation.
      Lymphatic invasion, PNI, extramural venous invasion, intramural venous invasion
      and tumour budding were determined in standard tissue slides. RESULTS: The
      presence of PNI (HR 3.36; 95% CI 1.82-6.21), extramural vascular invasion (HR
      1.93; 95% CI 1.17-3.19) and tumour budding (HR 1.83, 95% CI 1.11-3.03) was
      associated with a significant worse overall survival. The presence of >=2 adverse
      biomarkers resulted in a stronger prediction of adverse outcome in terms of
      overall survival (HR 2.82; 95% CI 1.66-4.79), disease-free survival (HR 2.27; 95%
      CI 1.47-3.48), and distant recurrence (HR 2.51; 95% CI 1.56-4.02). None of these
      markers alone or combined predicted a beneficial effect of adjuvant chemotherapy.
      DISCUSSION: We confirmed that several stage-independent biomarkers were
      significantly associated with a decreased outcome in rectal cancer patients. More
      importantly, these markers did not have predictive value and are thus not useful
      to select for adjuvant therapy in rectal cancer.

PMID- 29223020
TI  - Depressive symptoms, impaired glucose metabolism, high visceral fat, and high
      systolic blood pressure in a subgroup of women with recent gestational diabetes.
AB  - Women with gestational diabetes (GDM) are a high risk group for early type 2
      diabetes (T2D). Depression is a risk factor for T2D in the general population. We
      investigated in women after a recent pregnancy with GDM and without a clinical
      diagnosis of depression, whether mild to moderate depressive symptoms associate
      with pathologic glucose metabolism. In a cross-sectional analysis, we examined
      173 women, 9 +/- 3 months after delivery with several psychopathological
      assessments, 5-point oral glucose tolerance test with insulin, anthropometrics,
      and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was
      quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed
      mild to moderate depressive symptoms, and the proportion of women with pathologic
      glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D)
      was higher in this group than in the women without depressive symptoms (59.1% vs.
      33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index
      (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal
      visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021
      6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal
      visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after
      adjustment for BMI, associated with the presence of depressive symptoms. Taken
      together, we found depressive symptoms at a level not generally diagnosed in
      clinical practice in a subgroup of women with recent GDM. This subgroup also
      showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may
      therefore help to identify this special subgroup.

PMID- 29223021
TI  - Pre-treatment of soybean plants with calcium stimulates ROS responses and
      mitigates infection by Sclerotinia sclerotiorum.
AB  - Considering the high incidence of white mold caused by Sclerotinia sclerotiorum
      in a variety of field crops and vegetables, different control strategies are
      needed to keep the disease under economical threshold. This study assessed the
      effect of foliar application of a calcium formulation on disease symptoms, oxalic
      acid production, and on the oxidative stress metabolism in soybean plants
      inoculated with each of two isolates of the pathogen that have contrasting
      aggressiveness (HA, highly-aggressive versus WA, weakly-aggressive). Changes in
      reactive oxygen species (ROS) levels in soybean plants inoculated with S.
      sclerotiorum isolates were assessed at 6, 24, 48 and 72 h post inoculation (hpi).
      Generation of ROS including hydrogen peroxide (H2O2), anion superoxide (O2-) and
      hydroxyl radical (OH) was evaluated. Inoculation with the WA isolate resulted in
      more ROS accumulation compared to the HA isolate. Pre-treatment with the calcium
      formulation restored ROS production in plants inoculated with the HA isolate. We
      also noted a marked decrease in oxalic acid content in the leaves inoculated with
      the HA isolate in presence of calcium, which coincided with an increase in plant
      ROS production. The expression patterns of genes involved in ROS detoxification
      in response to the calcium treatments and/or inoculation with S. Sclerotiorum
      isolates were monitored by RT-qPCR. All of the tested genes showed a higher
      expression in response to inoculation with the WA isolate. The expression of most
      genes tested peaked at 6 hpi, which preceded ROS accumulation in the soybean
      leaves. Overall, these data suggest that foliar application of calcium
      contributes to a decrease in oxalic acid production and disease, arguably via
      modulation of the ROS metabolism.

PMID- 29223022
TI  - Next generation industrial biotechnology based on extremophilic bacteria.
AB  - Industrial biotechnology aims to produce bulk chemicals including polymeric
      materials and biofuels based on bioprocessing sustainable agriculture products
      such as starch, fatty acids and/or cellulose. However, traditional bioprocesses
      require bioreactors made of stainless steel, complicated sterilization, difficult
      and expensive separation procedures as well as well-trained engineers that are
      able to conduct bioprocessing under sterile conditions, reducing the
      competitiveness of the bio-products. Amid the continuous low petroleum price,
      next generation industrial biotechnology (NGIB) allows bioprocessing to be
      conducted under unsterile (open) conditions using ceramic, cement or plastic
      bioreactors in a continuous way, it should be an energy, water and substrate
      saving technology with convenient operation procedure. NGIB also requires less
      capital investment and reduces demand on highly trained engineers. The foundation
      for the simplified NGIB is microorganisms that resist contaminations by other
      microbes, one of the examples is rapid growing halophilic bacteria inoculated
      under high salt concentration and alkali pH. They have been engineered to produce
      multiple products in various scales.

PMID- 29223023
TI  - Live cell imaging reveals different modes of cytotoxic action of extracts derived
      from commonly used luting cements.
AB  - OBJECTIVE: To compare cytotoxicity of extracts derived from commonly used luting
      cements: Hoffmann's Zinc Phosphate (ZPC), GC Fuji Plus Resin Modified Glass
      Ionomer (RMGIC) and 3M ESPE RelyX Unicem Resin Cement (RC) on primary human
      gingival fibroblasts (HGFs). DESIGN: HGFs were exposed to different
      concentrations of the ZPC, RMGIC and RC extracts. The cytotoxicity was assessed
      with the PrestoBlue Cell Viability Reagent and viable cells were counted by a
      haemocytometer using the trypan blue exclusion test. In order to determine the
      primary mechanism of the cell death induced by extracts from different luting
      cements, the real-time monitoring of caspase-3/-7 activity and membrane integrity
      of cells was employed. RESULTS: The extracts from the RMGIC and ZPC decreased the
      metabolic activity and numbers of viable cells. Unexpectedly, the extracts from
      the RC evoked only small effects on the metabolic activity of HGFs with a
      decreasing number of viable cells in a dose-and time-dependent manner. The live
      cell imaging revealed that the apoptosis was the primary mechanism of a cell
      death induced by the extracts derived from the RMGIC, whereas the extracts from
      the RC and ZPC induced a cell death through a necrotic and caspase-independent
      pathway. CONCLUSIONS: The apoptosis was the primary mechanism of the cell death
      induced by the extracts derived from the RMGIC, whereas the extracts from the RC
      and ZPC induced a cell death via a necrotic pathway. We suggest that metabolic
      assays commonly used to assess the cytotoxicity of luting cements should be
      validated by alternative methods.

PMID- 29223024
TI  - Genomic integration and expression of the Aggregatibacter actinomycetemcomitans
      catalase gene in Aggregatibacter aphrophilus.
AB  - OBJECTIVE: To test the hypothesis that virulence genes of Aggregatibacter
      actinomycetemcomitans can be expressed and confer fitness advantages in the
      closely related Aggregatibacter aphrophilus. DESIGN: Clinical isolates of A.
      aphrophilus were screened for natural competence with marked genomic DNA from A.
      actinomycetemcomitans and A. aphrophilus. The gene katA of A.
      actinomycetemcomitans D7S-1 and its flanking regions were constructed and
      inserted into a comparable locus in the genome of a naturally competent A.
      aphrophilus strain by a markerless protocol via natural transformation. Mutants
      of A. actinomycetemcomitans with or without katA were also constructed by a
      similar protocol. Discs soaked with either 0.03% hydrogen peroxide or broth
      culture of Streptococcus gordonii Challis were placed on the agar with cultures
      of A. actinomycetemcomitans or A. aphrophilus. The size of the growth inhibition
      zone associated with the disc was measured after 2-day culture. RESULTS: Five of
      the 13A. aphrophilus strains exhibited a transformation frequency of 10-6 or
      higher. The intra- and inter-species transformation frequencies were comparable.
      The inhibition zones for katA-negative strains of A. actinomycetemcomitans or A.
      aphrophilus were 3- to 7-fold larger than those associated with katA-positive
      strains (p<0.05). CONCLUSIONS: There was no apparent species barrier for the
      transfer and expression of A. actinomycetemcomitans katA in A. aphrophilus. The
      inserted A. actinomycetemcomitans-specific katA gene in A. aphrophilus strain
      NJ8700 conferred resistance to inhibition by hydrogen peroxide or S. gordonii.
      The potential to swap genes between these two closely related oral species may be
      an alternative approach for investigating the virulence determinants of A.
      actinomycetemcomitans.

PMID- 29223026
TI  - Mandatory helmet legislation as a policy tool for reducing motorcycle fatalities:
      Pinpointing the efficacy of universal helmet laws.
AB  - This study uses repeated cross-sections of individual level crash data to study
      the effectiveness of motorcycle helmet legislation. Results suggest that
      motorcycle helmet laws reduce average individual fatality risks by 20.5%. From a
      policy standpoint, large states such as Florida and Texas can reduce annual
      motorcycle fatalities by an average 100 deaths through reinstating universal
      helmet laws. Valuing these fatality reductions at the U.S. DOT suggested $9.4
      million value of a statistical life yields aggregate annual state benefits of
      approximately $940 million. The effectiveness of helmet legislation can be
      attributed to the technological efficacy of helmets as well as enhancing behavior
      in the form of reduced risk taking among motorcyclists. Specifically,
      motorcyclists who use helmets in order to comply with mandatory helmet laws are
      29.8% less likely to receive a traffic citation for risky driving behavior
      (speeding, alcohol, etc.), travel at a 6 mph lower average speed, and have a
      47.4% reduction in the probability of "severely" damaging their motorcycle in a
      crash.

PMID- 29223025
TI  - The intersection between response inhibition and substance use among adolescents.
AB  - Problems related to the capacity to successfully engage response inhibition are
      considered a risk factor for the development of substance use disorders (SUDs),
      but the evidence has been predominantly cross-sectional. In this commentary, we
      argue that recent longitudinal studies with multi-modal measures of response
      inhibition can improve understanding of how response inhibition may intersect
      with substance use among adolescents. Most Stop-Signal studies suggest that
      slower response inhibition predicts substance use progressions, with one multi
      site study showing greater fronto-parietal activity indicative of risk. Most Go
      NoGo studies suggest that blunted activation of prefrontal cortical areas during
      response inhibition predicts substance use progressions, while commission errors
      are less effective in identifying adolescents at risk. Studies differ in subject
      populations, outcome measures, statistical methods, and BOLD response contrasts,
      which challenge the capacity to compare and generalize findings. We encourage
      research teams throughout the globe to undertake multi-modal, longitudinal
      studies to assess brain functioning with large sample sizes, and when possible,
      before significant substance use potentially obscures interpretation of findings.
      Systematic review and meta-analysis of this growing literature are also important
      goals for future research.

PMID- 29223027
TI  - Burden of injury of serious road injuries in six EU countries.
AB  - BACKGROUND: Information about the burden of (non-fatal) road traffic injury is
      very useful to further improve road safety policy. Previous studies calculated
      the burden of injury in individual countries. This paper estimates and compares
      the burden of non-fatal serious road traffic injuries in six EU
      countries/regions: Austria, Belgium, England, The Netherlands, the Rhone region
      in France and Spain. METHODS: It is a cross-sectional study based on hospital
      discharge databases. POPULATION: of study are patients hospitalized with MAIS3+
      due to road traffic injuries. The burden of injury (expressed in years lived with
      disability (YLD)) is calculated applying a method that is developed within the
      INTEGRIS study. The method assigns estimated disability information to the
      casualties using the EUROCOST injury classification. RESULTS: The average burden
      per MAIS3+ casualty varies between 2.4 YLD and 3.2 YLD per casualty. About 90% of
      the total burden of injury of MAIS3+ casualties is due to lifelong consequences
      that are experienced by 19% to 33% of the MAIS3+ casualties. Head injuries,
      spinal cord injuries and injuries to the lower extremities are responsible for
      more than 90% of the total burden of MAIS3+ road traffic injuries. Results per
      transport mode differ between the countries. Differences between countries are
      mainly due to differences in age distribution and in the distribution over
      EUROCOST injury groups of the casualties. CONCLUSION: The analyses presented in
      this paper can support further improvement of road safety policy. Countermeasures
      could for example be focused at reducing skull and brain injuries, spinal cord
      injuries and injuries to the lower extremities, as these injuries are responsible
      for more than 90% of the total burden of injury of MAIS3+ casualties.

PMID- 29223028
TI  - Accident rates and the impact of daylight saving time transitions.
AB  - One-third of nations have adopted some form of Daylight Saving Time (DST).
      Associated costs and benefits include impacts on accident rates. Using data from
      12.6 million accident claims in New Zealand during 2005-2016, we model accident
      rates as a function of various date-based predictors including days before/after
      the start and end of DST, holidays, day of week, and month of year. This is the
      first study to consider multiple accident categories (Road, Work, Falls and Home
      & Community), and the first in the southern hemisphere. The start of DST is
      associated with significantly higher rates of road accidents (first day +16% and
      second day +12%). Evidence that accident rates for Falls and Home & Community
      decline (increase) prior to the start (end) of DST suggest potential behavioural
      adaption from anticipating the change. While Work accidents show limited impact
      from DST changes, they exhibit a significant decline over the course of the week
      (Friday 13% lower than Monday), whereas Road accidents exhibit a significant
      increase (Friday 19% higher than Monday). Our results have implications for both
      DST implementation and policy.

PMID- 29223029
TI  - Design, synthesis and evaluation of novel N-hydroxybenzamides/N
      hydroxypropenamides incorporating quinazolin-4(3H)-ones as histone deacetylase
      inhibitors and antitumor agents.
AB  - In our search for novel small molecules targeting histone deacetylases, we have
      designed and synthesized several series of novel N-hydroxybenzamides/N
      hydroxypropenamides incorporating quinazolin-4(3H)-ones (4a-h, 8a-d, 10a-d).
      Biological evaluation showed that these hydroxamic acids were generally cytotoxic
      against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23,
      lung cancer). It was found that the N-hydroxypropenamides (10a-d) were the most
      potent, both in term of HDAC inhibition and cytotoxicity. Several compounds, e.g.
      4e, 8b-c, and 10a-c, displayed up to 4-fold more potent than SAHA
      (suberoylanilide hydroxamic acid, vorinostat) in term of cytotoxicity. These
      compounds also comparably inhibited HDACs with IC50 values in sub-micromolar
      range. Docking experiments on HDAC2 isozyme revealed some important features
      contributing to the inhibitory activity of synthesized compounds, especially for
      propenamide analogues. Importantly, the free binding energy computed was found to
      have high quantitative correlation (R2 ~ 95%) with experimental results.

PMID- 29223030
TI  - First evaluation of organotellurium derivatives as carbonic anhydrase I, II, IV,
      VII and IX inhibitors.
AB  - A series of tellurides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1)
      inhibitors against the human (h) carbonic anhydrase isoforms hCA I, II, IV, VII
      and IX, involved in a variety of diseases, including glaucoma, retinitis
      pigmentosa, epilepsy, arthritis and tumors. These compounds, which are the first
      tellurium-containing derivatives acting as inhibitors of carbonic anhydrase
      enzymes, showed effective inhibition against all isoforms investigated and some
      of them were selective for inhibiting the cytosolic or the membrane-bound CAs.
      Thus, these carbonic anhydrase inhibitors are interesting leads for the
      development of isoform-selective inhibitors.

PMID- 29223031
TI  - Protonography and anion inhibition profile of the alpha-carbonic anhydrase
      (CruCA4) identified in the Mediterranean red coral Corallium rubrum.
AB  - CruCA4 is a secreted isoform of the alpha-carbonic anhydrase (CA, EC 4.2.1.1)
      family, which has been identified in the octocoral Corallium rubrum. This enzyme
      is involved in the calcification process leading to the formation of the coral
      calcium carbonate skeleton. We report here experiments performed on the
      recombinant CruCA4 with the technique of protonography that can be used to detect
      in a simple way the enzyme activity. We have also investigated the inhibition
      profile of CruCA4 with one major class of CA inhibitors, the inorganic anions. A
      range of weak and moderate inhibitors have been identified having KI in the range
      of 1-100 mM, among which the halides, pseudohalides, bicarbonate, sulfate,
      nitrate, nitrite, and many complex inorganic anions. Stronger inhibitors were
      sulfamide, sulfamate, phenylboronic acid, phenylarsonic acid, and
      diethylditiocarbamate, which showed a better affinity for this enzyme, with KI in
      the range of 75 MUM-0.60 mM. All these anions/small molecules probably coordinate
      to the Zn(II) ion within the CA active site as enzyme inhibition mechanism.

PMID- 29223033
TI  - The mediating role of cognitive ability on the relationship between motor
      proficiency and early academic achievement in children.
AB  - The aim of this study was to examine the relationship between motor proficiency
      and academic achievement in 7 years-old children. A mediating model in which the
      relation between motor proficiency and academic achievement is mediated by
      cognitive ability was tested. Participants included 152 children from the
      longitudinal study Jeunes enfants et leurs milieux de vie (Young Children and
      their Environments). Motor proficiency was evaluated with the Bruininks-Oseretsky
      Test of Motor Proficiency (BOT2), cognitive ability with the Wechsler
      Intelligence Scale for Children-Fourth Edition (WISC-IV) and academic achievement
      with the Wechsler Individual Achievement Test II (WIAT II). Results showed that
      motor proficiency, cognitive ability and academic achievement were positively
      correlated with each other. A structural equation modeling analysis revealed that
      motor proficiency had a positive effect on academic achievement through an
      indirect path via cognitive ability. These results highlight the fundamental
      importance of motor skills in children's academic achievement in early school
      years.

PMID- 29223032
TI  - DNA Replication and associated repair pathways are involved in the mutagenesis of
      methylated cytosine.
AB  - Transitions of cytosine to thymine in CpG dinucleotides are the most frequent
      type of mutations observed in cancer. This increased mutability is commonly
      explained by the presence of 5-methylcytosine (5mC) and its spontaneous
      hydrolytic deamination into thymine. Here, we describe observations that question
      whether spontaneous deamination alone causes the elevated mutagenicity of 5mC.
      Tumours with somatic mutations in DNA mismatch-repair genes or in the
      proofreading domain of DNA polymerase epsilon (Pol epsilon) exhibit more 5mC to T
      transitions than would be expected, given the kinetics of hydrolytic deamination.
      This enrichment is asymmetrical around replication origins with a preference for
      the leading strand template, in particular in methylated cytosines flanked by
      guanines (GCG). Notably, GCG to GTG mutations also exhibit strand asymmetry in
      mismatch-repair and Pol epsilon wild-type tumours. Together, these findings
      suggest that mis-incorporation of A opposite 5mC during replication of the
      leading strand might be a contributing factor in the mutagenesis of methylated
      cytosine.

PMID- 29223034
TI  - Effect of caliber size and fat level on the inactivation of E. coli O157:H7 in
      dry fermented sausages.
AB  - Dry fermented sausages (DFS) have been subject to numerous validation studies, as
      pathogen reduction heavily relies on both ingredients and processing. In this
      study the effect of product caliber size (32, 55, 80mm), and fat level (low,
      9.67%; high, 18.46% wt/wt) on the inactivation of E. coli O157:H7 during DFS
      production was examined. Sausages containing a five-strain cocktail of E. coli
      O157:H7 at 107CFU/g were manufactured and monitored for changes in
      physicochemical properties and inoculated E. coli O157:H7 numbers were enumerated
      during the DFS production stages and log reduction rates were calculated.
      Significant (P<0.01) reduction in pH from 5.9 to 4.9 was observed in all sausages
      within 72h of fermentation; however, the observed pH reduction was not
      significantly (P>0.05) different among sausages of different caliber size or fat
      levels. No significant (P>0.05) reduction in aw was observed during fermentation
      of the sausages. However, during the drying phase, sausages with larger caliber
      sizes required a significantly longer duration of drying to achieve the same aw
      of smaller caliber size sausages. For instance, to achieve an aw of <=0.9,
      following 5days of fermentation/curing, 80mm caliber sausages required up to
      27days of drying compared with 13 and 6days for 55 and 32mm caliber size
      sausages, respectively. Fat levels on the other hand did not significantly
      (P>0.05) effect the reduction of aw during drying of the sausages. During the
      fermentation stage there was a significant and rapid reduction in E. coli O157:H7
      counts by about 1.1- to 1.4-log units, but was not significantly different among
      sausages of different caliber size and fat levels. Considering the whole process,
      only caliber size had a significant effect on log reduction of E. coli O157:H7.
      ANOVA of log reduction rates of E. coli O157:H7 among sausages of different
      caliber size and fat levels revealed no significant differences during the
      fermentation, however, during the drying of the sausages, log reduction rate of
      E. coli O157:H7 was significantly (P<0.01) lower in sausages with larger caliber
      sizes and higher fat levels. For instance, log reduction rates for E. coli
      O157:H7 in high fat large caliber sausages was the lowest at -0.082+/-0.004 log
      CFU/g/day compared to all other fat and caliber size combinations. These results
      suggest that DFS manufacturers producing higher fat and large caliber size
      products need to consider longer drying periods to achieve the required 5-log
      inactivation of E. coli O157:H7.

PMID- 29223035
TI  - Use of hop extract as antifungal ingredient for bread making and selection of
      autochthonous resistant starters for sourdough fermentation.
AB  - Aiming at meeting the consumers' demand in terms of bio-preservation, the
      potential of the combination of the lactic acid bacteria fermentation and the
      addition of hop extract as natural preservative in breadmaking, was exploited.
      The antifungal properties of a hop (Humulus lupulus) extract were investigated,
      showing a significant inhibition of the hyphal growth of Aspergillus parasiticus,
      Penicillium carneum, Penicillium polonicum, Penicillium paneum, Penicillium
      chermesinum, Aspergillus niger, Penicillium roqueforti. Lactic acid bacteria
      belonging to species of Enterococcus feacium, Lactobacillus plantarum,
      Lactobacillus brevis, Lactobacillus helveticus, Lactobacillus curvatus,
      Pediococcus pentosaceus, and Pediococcus acidilactici were isolated from hop and
      subjected to selection based on kinetics of growth and acidification. The
      sourdough (hS) enriched with hop extract (hE), started with three selected
      strains, had phenols concentration and antioxidant activity higher than those
      obtained in the same condition but without the hE. Hop-sourdough used in
      breadmaking delayed the fungal growth (14 days), giving a bread characterized by
      free aminoacids concentration, antioxidant and phytase activities higher than
      bread started only with baker's yeast, with or without the addition of hE.
      Specific volume and cell-total area of the bread containing hE improved, and its
      sensory profile was characterized by typical sourdough attributes, and a moderate
      bitter/herbaceous perception.

PMID- 29223036
TI  - Study on temperature and near-infrared driving characteristics of hydrogel
      actuator fabricated via molding and 3D printing.
AB  - A hydrogel material system which was fit for molding and 3D printing was
      developed to fabricate bilayer hydrogel actuators with controllable temperature
      and near infrared laser responses. Polymerization on interface boundary of
      layered structure enhanced the bonding strength of hydrogel actuators. By
      utilizing anisotropic of microstructure along with thickness direction, bilayer
      hydrogel actuators fabricated via molding realized intelligent bending/shrinking
      responses, which guided the preparation of hydrogel ink for 3D printing. In-situ
      free radical polymerization under vacuum realized the solidification of printed
      hydrogel actuators with graphene oxide. Based on anisotropic swelling/deswelling
      behaviors of precise structure fabricated via 3D printing, the printed bilayer
      hydrogel actuators achieved temperature and near infrared laser responsive
      deformation. Changes of programmable printing path effectively resulted in
      corresponding deformation patterns. Combination of advantages of molding and 3D
      printing can promote the design and fabrication of hydrogel actuators with high
      mechanical strength, response speed and deformation ability.

PMID- 29223037
TI  - A microfabricated platform for the study of chondrogenesis under different
      compressive loads.
AB  - Microfluidic devices are beneficial in miniaturizing and multiplexing various
      cellular assays in a single platform. Chondrogenesis is known to pertain to
      chemical, topographical, and mechanical cues in the microenvironment. Mechanical
      cues themselves have numerous parameters such as strain magnitude, frequency, and
      stimulation time. Effects of different strain magnitudes on the chondrogenic
      differentiation of adult stem cells have not been explored thoroughly. Here, a
      new multilayer microdevice is presented for the unidirectional compressive
      stimulation of cells in a three-dimensional cell culture. Numerical simulations
      were performed to evaluate and optimize the design. Results showed a favorable
      highly uniform axial strain distribution and negligible radial and
      circumferential strain for the optimized design. Moreover, an experimental study
      was performed on rabbit adipose-derived stem cells encapsulated in-situ in
      alginate hydrogel. Strain levels of 20%, 15%, 10%, 5%, and 0% were studied
      simultaneously on a microfluidic platform. Dynamic mechanical compression
      positively influenced cellular viability and upregulated collagen II, Sox-9, and
      aggrecan expression in the absence of exogenous growth factors. The expression of
      collagen type II as specific marker for articular chondrocytes was further
      confirmed by immunofluorescence staining of collagen type II. Taking together,
      10% strain can be considered as optimal stimulation factor for chondrogenic
      differentiation of adipose derived stem cells.

PMID- 29223038
TI  - Polymer matrix of fiber-reinforced composites: Changes in the semi
      interpenetrating polymer network during the shelf life.
AB  - This laboratory study was aimed to characterize semi-interpenetrating polymer
      network (semi-IPN) of fiber-reinforced composite (FRC) prepregs that had been
      stored for up to two years before curing. Resin impregnated prepregs of everStick
      C&B (StickTech-GC, Turku, Finland) glass FRC were stored at 4 degrees C for
      various lengths of time, i.e., two-weeks, 6-months and 2-years. Five samples from
      each time group were prepared with a light initiated free radical polymerization
      method, which were embedded to its long axis in self-curing acrylic. The
      nanoindentation readings on the top surface toward the core of the sample were
      made for five test groups, which were named as "stage 1-5". To evaluate the
      nanohardness and modulus of elasticity of the polymer matrix, a total of 4 slices
      (100um each) were cut from stage 1 to stage 5. Differences in nanohardness values
      were evaluated with analysis of variance (ANOVA), and regression model was used
      to develop contributing effect of the material's different stages to the total
      variability in the nanomechanical properties. Additional chemical and thermal
      characterization of the polymer matrix structure of FRC was carried out. It was
      hypothesized that time of storage may have an influence on the semi-IPN polymer
      structure of the cured FRC. The two-way ANOVA test revealed that the storage time
      had no significant effect on the nanohardness of FRC (p = 0.374). However, a
      highly significant difference in nanohardness values was observed between the
      different stages of FRC (P<0.001). The regression coefficient suggests
      nanohardness increased on average by 0.039GPa for every storage group. The
      increased nanohardness values in the core region of 6-months and 2-years stored
      prepregs might be due to phase-segregation of components of semi-IPN structure of
      FRC prepregs before their use. This may have an influence to the surface bonding
      properties of the cured FRC.

PMID- 29223039
TI  - N-acetyl-l-cysteine ameliorates the PM2.5-induced oxidative stress by regulating
      SIRT-1 in rats.
AB  - Silent information regulator 1 (SIRT1), a class III histone deacetylase, plays a
      major role in combating cellular oxidative stress injury. However, the role of
      SIRT1 in oxidative stress induced by particulate matter remains unclear. A total
      of 32 healthy male Sprague-Dawley rats were divided into PM2.5, PM2.5+NAC,
      filtered air (control), and filtered air+NAC (NAC control) groups. The
      expressions of MnSOD, SIRT1, and FOXO3a were examined at both transcriptional and
      protein levels. The expression levels of MnSOD, SIRT1, and FOXO3a reduced
      significantly (P<0.05) in the PM2.5 group as compared to the control group.
      However, their expression levels were increased after NAC intervention. These
      results suggested that SIRT1 exerted a protective effect against PM2.5-induced
      respiratory oxidative damage by regulating the expression of FOXO3a. NAC can
      activate SIRT1 and exert an anti-oxidative role in PM2.5-induced oxidative
      injury.

PMID- 29223040
TI  - The Ascidian Embryo Teratogenicity assay in Ciona intestinalis as a new
      teratological screening to test the mixture effect of the co-exposure to ethanol
      and fluconazole.
AB  - The aim of this work was to evaluate the Ascidian Embryo Teratogenicity assay
      (AET) as new alternative invertebrate model to test the developmental effects of
      the co-exposure to ethanol and fluconazole. Ciona intestinalis embryos were
      exposed to the azolic fungicide fluconazole, (FLUCO, 7.8-250MUM), to ethanol
      (Eth, 0.01-0.5%) and to their mixture (0.01% Eth+FLUCO 7.8-250MUM) from neurula
      to larval stage. At the end of the exposure period, larvae were morphologically
      evaluated and benchmark analysis performed by using the PROAST modelling
      software. Both compounds were teratogenic in a concentration-related manner,
      particularly affecting the pigmented organs. The co-exposure to Eth enhanced the
      effects of FLUCO, the additive hypothesis was not rejected by the modelling. The
      results demonstrated that AET could be considered a good vertebrate-free
      alternative model for toxicological investigation in embryos.

PMID- 29223041
TI  - Understanding motivations for dietary supplementation during pregnancy: A focus
      group study.
AB  - OBJECTIVE: to increase understanding of psychosocial factors (behavioural,
      normative and control beliefs) motivating vitamin and mineral supplement use
      during pregnancy. DESIGN: ten focus group discussions and two in-depth interviews
      were conducted using a script comprising questions based on study objectives. All
      discussions were recorded, transcribed verbatim and analysed using a framework
      approach. SETTING: South Australia, Australia. SUBJECTS: 40 women aged 21-45
      years who were either pregnant or<12 months postpartum. Groups were stratified by
      education level (secondary education only vs. post-secondary) and gravidity
      (first vs. subsequent pregnancy). RESULTS: all women, except one, used dietary
      supplements during pregnancy. Most women took supplements to achieve peace of
      mind knowing that nutrient requirements were 'definitely' being met. Other common
      factors motivating supplement use were the beliefs that supplementation: benefits
      maternal and fetal health; corrects known nutritional deficiencies; and is a more
      efficient method of obtaining required nutrients relative to food. Advice
      received from healthcare providers and marketing of supplements also motivated
      supplementation, while forgetting to take supplements was the most common barrier
      to use. Cost was only a barrier when considering whether or not to continue
      supplementation post-birth. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: women
      believe that supplements are an easier and more reliable source of nutrients than
      food intake alone, and rely on dietary supplementation as an insurance policy
      during pregnancy. Further studies are needed in larger and more representative
      samples to validate these findings and to test the effectiveness of information
      and intervention strategies targeting appropriate supplement use during
      pregnancy.

PMID- 29223042
TI  - Experiences of early labour management from perspectives of women, labour
      companions and health professionals: A systematic review of qualitative evidence.
AB  - OBJECTIVES: to examine evidence of women's, labour companions' and health
      professionals' experiences of management of early labour to consider how this
      could be enhanced to better reflect women's needs. DESIGN: a systematic review of
      qualitative evidence. SETTING AND PARTICIPANTS: women in early labour with term,
      low risk singleton pregnancies, not booked for a planned caesarean birth or post
      dates induction of labour, their labour companions, and health professionals
      responsible for early labour care (e.g. midwives, nurse-midwives, obstetricians,
      family doctors). Studies from high and middle income country settings were
      considered. FINDINGS: 21 publications were included from the UK, Ireland,
      Scandinavia, USA, Italy and New Zealand. Key findings included the impact of
      communication with health professionals (most usually midwives) on women's
      decision making; women wanting to be listened to by sympathetic midwives who
      could reassure that symptoms and signs of early labour were 'normal' and offer
      clear advice on what to do. Antenatal preparation which included realistic
      information on what to expect when labour commenced was important and appreciated
      by women and labour companions. Views of the optimal place for women to remain
      and allow early labour to progress differed and the perceived benefit of support
      and help offered by labour companions varied. Some were supportive and helped
      women to relax, while others were anxious and encouraged women to seek early
      admission to the planned place of birth. Web-based sources of information are
      increasingly used by women, with mixed views of the value of information
      accessed. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: women, labour companions
      and health professionals find early labour difficult to manage well, with women
      unsure of how decisions about admission to their planned place of birth are
      taken. It is unclear why women are effectively left to manage this aspect of
      their labour with minimal guidance or support. Tailoring management to meet
      individual needs, with provision of effective communication could reassure women
      and facilitate timely admission from perspectives of women, their companions,
      midwives and other health professionals. Information on labour onset and
      progress, and approaches to pain management, should be shared with women's labour
      companions to enable them to feel more confident to better support women. Further
      research is needed of the impact of different models of care and increasing use
      of web-based information on women's approaches to self-management when labour
      commences. PROSPERO 2014 CRD 42014009745.

PMID- 29223043
TI  - Affect toward the self and self-injury stimuli as potential risk factors for
      nonsuicidal self-injury.
AB  - Few risk factors for nonsuicidal self-injury (NSSI) have been identified. This
      study investigated diminished aversion toward self-injury (i.e., NSSI,
      suicide/death stimuli) and self-criticism as unique NSSI risk factors. After
      terminating a treatment study, 154 adults with a recent and frequent NSSI history
      completed self-report and computer-based measures of psychopathology, implicit
      and explicit self-criticism, and implicit aversion to NSSI and suicide/death.
      Participants were then contacted 4 weeks later to test factors predicting NSSI
      frequency over this follow-up period. Diminished aversion toward NSSI stimuli and
      self-criticism significantly predicted NSSI 4 weeks later. These effects were
      unique from other theoretically important predictors, such as past week NSSI
      frequency and total number of NSSI methods used. Findings provide support that
      erosion of barriers to NSSI (e.g., aversion to self-injurious stimuli, decreased
      self-worth) may facilitate continued engagement in these dangerous behaviors.
      Results shed light on potential treatment targets for NSSI.

PMID- 29223044
TI  - Association between sleep disorder and panic disorder in South Korea: Nationwide
      nested case-control study of data from 2004 to 2013.
AB  - After 2010, panic disorders became relatively common in South Korea, with many
      celebrities confessing to the public that they have panic disorder. The annual
      number of patients with panic disorder and sleep disorder have been gradually
      increasing. In light of these increases, we analyzed the relationship between
      sleep disorder and panic disorder. We used national claim data to design a 1:3
      nested case-control study. The study included medical claims filed for 29,312
      patients during 2004-2013. We performed conditional logistic regression analysis
      to investigate the relationship between sleep disorder and panic disorder. There
      were 7436 patients who were diagnosed with panic disorder, and 21,876 patients
      who were gender- and age-matched as controls. Patients with sleep disorder had
      higher incidence of panic disorder. In particular, patients with insomnia had the
      strongest association with panic disorder (adjusted, OR, 1.386; 95% CI, 1.201
      1.599; p < 0.05). These associations were stronger in healthy patients and those
      with worse socioeconomic status. In conclusion, sleep disorder, in particular,
      insomnia was positively associated with panic disorder. Thus, healthcare
      professionals and policy makers should effectively control insomnia and consider
      strategies for early intervention for vulnerable patients with risk of panic
      disorder.

PMID- 29223045
TI  - Investigation of antioxidant ability of grape seeds extract to prevent
      oxidatively induced DNA damage by gas chromatography-tandem mass spectrometry.
AB  - Phenolic compounds have been studied elaborately for their efficacy to improve
      health and to protect against a wide variety of diseases. Herein this study,
      different analysis methods were implemented to evaluate the antioxidant
      properties of catechin and cyanidin using their standard substances and as they
      found in the grape seeds extracts. Total phenol contents were 107.39+/-8.94mg
      GAE/g dw of grape seeds for grape seed extract (GSE) and 218.32+/-10.66mg GAE/g
      dw of grape seeds for acid-hydrolyzed grape seed extract (AcGSE). The extracts
      were analyzed by HPLC-DAD system and the results showed the presence of catechin,
      gallic acid, chlorogenic acid and ellagic acid in the processed methanolic
      extract and cyanidin, gallic acid and ellagic acid in the processed acidified
      methanolic extract. The protective abilities of catechin and cyanidin were tested
      against the oxidation of DNA. The results showed that cyanidin has better
      protection of DNA against oxidation than catechin. GSE and AcGSE were revealed to
      inhibit the oxidatively induced DNA damage. GSE decreased about 57% of damage
      caused by the Fenton control sample. This study could show new aspects of the
      antioxidant profiles of cyanidin and catechin.

PMID- 29223046
TI  - Cohort-friendly protocol for a sensitive and fast method for trihalomethanes in
      urine using gas chromatography-Triple quadrupole mass spectrometry.
AB  - A cohort-friendly biomonitoring protocol has been developed for measuring
      biomarkers of exposure to disinfection by-products (trihalomethanes, THM) in
      urine using small initial volume (3mL) and short analysis time (~10min) that
      facilitates the throughput of a large number of samples. The objective of this
      study was to optimise a cohort-friendly biomonitoring protocol for the
      determination of four THM analytes in human urine using gas chromatography
      coupled with triple quadrupole mass spectrometry (GC-QqQ-MS/MS). The proposed
      methodology will facilitate the inclusion of such urinary THM measurements into
      large population health studies.

PMID- 29223047
TI  - Identification and analysis of a mercapturic acid conjugate of indole-3-methyl
      isothiocyanate in the urine of humans who consumed cruciferous vegetables.
AB  - Glucobrassicin, a quantitatively significant constituent of Brassica vegetables,
      gives rise to indole-3-carbinol (I3C) and its dimer di-indolylmethane (DIM) when
      the vegetables are chewed. I3C and DIM have been extensively studied with respect
      to their anti-carcinogenic properties. However, the presumed intermediate
      isothiocyanate in their formation, indole-3-methyl isothiocyanate (IMITC), has to
      our knowledge never been observed, despite the fact that isothiocyanates derived
      from cruciferous vegetables are known to have anti-carcinogenic properties.
      Therefore, we investigated the formation and presence in human urine of IMITC by
      analyzing for its N-acetylcysteine conjugate, IMITC-NAC, in order to gain a more
      complete understanding of the biochemical pathways leading to formation of I3C
      and DIM upon consumption of vegetables rich in glucobrassicin. Standard IMITC-NAC
      was synthesized and its structure confirmed by NMR and MS. IMITC-NAC was
      identified in extracts of Brussels sprouts chopped in the presence of N
      acetylcysteine. An LC-ESI-MS/MS-SRM method for analysis of IMITC-NAC, with
      [13C,15N]IMITC-NAC as internal standard, was developed and validated. Then, ten
      subjects (7 females) consumed a salad of Brussels sprouts and cabbage (containing
      100-500MUmol glucobrassicin) once daily for 3days. Urine was collected at
      intervals up to 24h after vegetable consumption. Levels of IMITC-NAC in the urine
      of these 10 subjects ranged from 0.2 to 30.2pmol/mL urine. These results provide
      the first evidence for the presumed intermediacy of IMITC in the formation of I3C
      and DIM in humans who consumed Brussels sprouts and cabbage as a source of
      glucobrassicin.

PMID- 29223048
TI  - Extraction protocol and liquid chromatography/tandem mass spectrometry method for
      determining micelle-entrapped paclitaxel at the cellular and subcellular levels:
      Application to a cellular uptake and distribution study.
AB  - Paclitaxel-loaded polymeric micelles (PTX-PM) are commonly used as tumor-targeted
      nanocarriers and display outstanding antitumor features in clinic, but its
      accumulation and distribution in vitro are lack of investigation. It is probably
      due to the complex micellar system and its low concentration at the cellular or
      subcellular levels. In this study, we developed an improved extraction method,
      which was a combination of mechanical disruption and liquid-liquid extraction
      (LLE), to extract the total PTX from micelles in the cell lysate and subcellular
      compartments. An ultra-performance liquid chromatography tandem mass spectroscopy
      (UPLC-MS/MS) method was optimized to detect the low concentration of PTX at
      cellular and subcellular levels simultaneously, using docetaxel as internal
      standard (IS). The method was proved to release PTX totally from micelles
      (>=95.93%) with a consistent and reproducible extraction recovery (>=75.04%).
      Good linearity was obtained at concentrations ranging from 0.2 to 20ng/mL. The
      relative error (RE%) for accuracy varied from 0.68 to 7.56%, and the intra- and
      inter-precision (relative standard deviation, RSD%) was less than 8.64% and
      13.14%, respectively. This method was fully validated and successfully applied to
      the cellular uptake and distribution study of PTX-loaded PLGA-PEG micelles in
      human breast cancer cells (MCF-7).

PMID- 29223049
TI  - Determination of blood concentrations of main active compounds in Zi-Cao-Cheng-Qi
      decoction and their total plasma protein binding rates based on hollow fiber
      liquid phase microextraction coupled with high performance liquid chromatography.
AB  - Oil-in-salt hollow fiber liquid phase microextraction coupled with high
      performance liquid chromatography ultraviolet detection (HPLC-UV) was developed
      for determination of the blood concentrations of the main active compounds,
      hesperidin, honokiol, shikonin, magnolol, emodin and beta,beta'
      dimethylacrylshikonin, after oral administration of Zi-Cao-Cheng-Qi decoction
      (ZCCQD) and their total plasma protein binding rates. In the procedure, a hollow
      fiber segment was immersed in organic solvent to fill the solvent in the fiber
      lumen and wall pore, and then the fiber was immersed into sodium chloride
      solution to cover a thin salt membrane on the fiber wall pore filling organic
      solvent. Various factors affecting the procedure, such as extraction solvent,
      sample phase pH, stirring rate, extraction time, NaCl concentration and fiber
      immersion time in the NaCl solution, were optimized. Under the optimum
      conditions, good linearities (r2>=0.9905), low limits of detection (0.7-2.5ng/mL)
      or quantitation (1.2-12ng/mL), satisfactory precision (2.6%-12.8%) and accuracy
      (81.0%-114.2%) of this method, were observed. The results showed that, after oral
      administration of a 25g/kg dose, (1) the blood concentrations (at 0.5h) of
      hesperidin, honokiol, shikonin, magnolol, emodin and beta,beta'
      dimethylacrylshikonin were 0.45, 0.40, 0.48, 0.74, 0.11 and 1.11MUg/mL,
      respectively; (2) the total plasma protein binding rates of the six active
      compounds were 42.0% (hesperidin), 71.8% (honokiol), 64.6% (shikonin), 77.7%
      (magnolol), 75.3% (emodin) and 75.7% (beta,beta'-dimethylacrylshikonin),
      respectively. The proposed procedure coupled with HPLC shows obvious advantages,
      such as low solvent consumption, simple operation, high sensitivity and strong
      purifying and can be used for the determination of both the blood concentrations
      and total plasma protein binding rates of active compounds in traditional Chinese
      medicine.

PMID- 29223050
TI  - A simple, rapid and stability indicating validated method for quantification of
      lamotrigine in human plasma and dry plasma spot using LC-ESI-MS/MS: Application
      in clinical study.
AB  - Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic
      drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of
      epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical
      tool in optimization of overall therapy. However, TDM is challenging due to the
      high biological samples (plasma/blood) storage/shipment costs and the limited
      availability of laboratories providing TDM services. Sampling in the form of dry
      plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome
      these issues. We developed and validated a new method for quantification of LTZ
      in human plasma and DPS. The extraction of LTZ from plasma and DPS was performed
      using liquid-liquid extraction with diethyl ether and an extraction solution
      composed of diethyl ether- methyl tert-butyl ether- acetone (50:30:20, v/v/v),
      respectively. Lamotrigine- 13C3, d3 was used as internal standard (ISTD) and the
      chromatographic separation was achieved on Hypurity Advance C18 column
      (150*4.6mm, 5MUm). Quantitative estimation of LTZ and ISTD was performed on a
      liquid chromatography tandem mass spectrometer coupled with electrospray
      ionization interface operated under positive mode of ionization. Calibration
      curves were linear (r2>0.99) over the concentration range of 10-3020ng/mL for
      both plasma and DPS. Statistical analysis provides insignificant difference
      between LTZ concentration extracted from plasma and DPS samples. The method is
      found suitable for application in clinical study and in therapeutic monitoring of
      LTZ. To the best of our knowledge this is the first report which describing a
      validated stability indicating assay for quantification of LTZ in dry plasma
      spot.

PMID- 29223051
TI  - Ultrasensitive colorimetric immunoassay for hCG detection based on dual catalysis
      of Au@Pt core-shell nanoparticle functionalized by horseradish peroxidase.
AB  - In this paper, an ultrasensitive colorimetric biosensor for human chorionic
      gonadotrophin (hCG) detection was designed from bottom-up method based on the
      dual catalysis of the horseradish peroxidase (HRP) and Au@Pt nanoparticles (NPs)
      relative to H2O2-TEM system. HRP and monoclonal mouse anti-hCG antibody (beta
      submit, mAb1) were co-immobilized onto the Au@Pt NP surface to improve catalytic
      efficiency and specificity, which formed a dual functionalized Au@Pt-HRP probe
      with the mean size of 42.8nm (D50). The colorimetric immunoassay was developed
      for the hCG detection, and the Au@Pt-HRP probe featured a higher sensitivity in
      the concentration range of 0.4-12.8IUL-1 with a low limit of detection (LOD) of
      0.1IUL-1 compared with the LODs of 0.8IUL-1 for BA-ELISA and of 2.0IUL-1 for
      Au@Pt, which indicated that the Au@Pt-HRP probe possessed higher catalytic
      efficiency with 2.8-fold increase over Au@Pt and 33.8-fold increase over HRP.
      Also, the Au@Pt-HRP probe exhibited good precision and reproducibility, high
      specificity and acceptable accuracy with CV being less than 15%. The dual
      functionalized Au@Pt-HRP probe as a type of signal amplified method was firstly
      applied in the colorimetric immunoassay for the hCG detection.

PMID- 29223052
TI  - Wavelength selection for portable noninvasive blood component measurement system
      based on spectral difference coefficient and dynamic spectrum.
AB  - Noninvasive blood component analysis by spectroscopy has been a hotspot in
      biomedical engineering in recent years. Dynamic spectrum provides an excellent
      idea for noninvasive blood component measurement, but studies have been limited
      to the application of broadband light sources and high-resolution spectroscopy
      instruments. In order to remove redundant information, a more effective
      wavelength selection method has been presented in this paper. In contrast to many
      common wavelength selection methods, this method is based on sensing mechanism
      which has a clear mechanism and can effectively avoid the noise from acquisition
      system. The spectral difference coefficient was theoretically proved to have a
      guiding significance for wavelength selection. After theoretical analysis, the
      multi-band spectral difference coefficient-wavelength selection method combining
      with the dynamic spectrum was proposed. An experimental analysis based on
      clinical trial data from 200 volunteers has been conducted to illustrate the
      effectiveness of this method. The extreme learning machine was used to develop
      the calibration models between the dynamic spectrum data and hemoglobin
      concentration. The experiment result shows that the prediction precision of
      hemoglobin concentration using multi-band spectral difference coefficient
      wavelength selection method is higher compared with other methods.

PMID- 29223053
TI  - Pressure-induced phase transition and fracture in alpha-MoO3 nanoribbons.
AB  - MoO3 nanoribbons were studied under different pressure conditions ranging from 0
      to 21GPa at room temperature. The effect of the applied pressure on the
      spectroscopic and morphologic properties of the MoO3 nanoribbons was investigated
      by means of Raman spectroscopy and scanning electron microscopy techniques. The
      pressure dependent Raman spectra of the MoO3 nanoribbons indicate that a
      structural phase transition occurs at 5GPa from the orthorhombic alpha-MoO3 phase
      (Pbnm) to the monoclinic MoO3-II phase (P21/m), which remains stable up to 21GPa.
      Such phase transformation occurs at considerably lower pressure than the critical
      pressure for alpha-MoO3 microcrystals (12GPa). We suggested that the applanate
      morphology combined with the presence of crystalline defects in the sample play
      an important role in the phase transition of the MoO3 nanoribbons. Frequencies
      and linewidths of the Raman bands as a function of pressure also suggest a
      pressure-induced morphological change and the decreasing of the nanocrystal size.
      The observed spectroscopic changes are supported by electron microscopy images,
      which clearly show a pressure-induced morphologic change in MoO3 nanoribbons.

PMID- 29223054
TI  - Optimizing adsorption of blue pigment from wastewater by nano-porous modified Na
      bentonite using spectrophotometry based on response surface method.
AB  - This work highlighted the effective activation of bentonite paste to produce nano
      porous powder for removal of cationic dye from wastewater. The effects of
      activation parameters such as soda and moisture contents, ageing time and
      temperature were analyzed using response surface methodology (RSM). The
      significance of independent variables and their interactions were tested by
      blending the obtained powders with wastewater and then the adsorption was
      evaluated, spectrophotometrically. The experiments were carried out by
      preparation of pastes according to response surface methodology and central
      composite design, which is the standard method, was used to evaluate the effects
      and interactions of four factors on the treatment efficiency. RSM was
      demonstrated as an appropriate approach for optimization of alkali activation.
      The optimal conditions obtained from the desirable responses were 5.0wt% soda and
      45.0wt% moisture, respectively in which the powder activation was carried out at
      150 degrees C. In order to well understand the role of nano-structured material
      on dye removal, the adsorbents were characterized through X-ray diffraction,
      Fourier transform infrared spectroscopy, scanning electron microscopy and
      Brunauer-Emmett-Teller surface area measurement. Finally, the analysis clearly
      demonstrates that the dye removal onto prepared adsorbent is well fitted with
      Langmuir isotherm compared to the other isotherm models. The low cost of material
      and facile process support the further development for commercial application
      purpose.

PMID- 29223055
TI  - Structure elucidation and degradation kinetic study of Ofloxacin using surface
      enhanced Raman spectroscopy.
AB  - A simple, fast and sensitive surface enhanced Raman spectroscopy (SERS) method
      for quantitative determination of fluoroquinolone antibiotic Ofloxacin (OFX) is
      presented. Also the stability behavior of OFX was investigated by monitoring the
      SERS spectra of OFX after various degradation processes. Acidic, basic and
      oxidative force degradation processes were applied at different time intervals.
      The forced degradation conditions were conducted and followed using SERS method
      utilizing silver nanoparticles (Ag NPs) as a SERS substrate. The Ag NPs colloids
      were prepared by reduction of silver nitrate using polyethyelene glycol (PEG) as
      a reducing and stabilizing agent. Validation tests were done in accordance with
      International Conference on Harmonization (ICH) guidelines. The calibration curve
      with a correlation coefficient (R=0.9992) was constructed as a relationship
      between the concentration range of OFX (100-500ng/ml) and SERS intensity at
      1394cm-1 band. LOD and LOQ values were calculated and found to be 23.5ng/ml and
      72.6ng/ml, respectively. The developed method was applied successfully for
      quantitation of OFX in different pharmaceutical dosage forms. Kinetic parameters
      were calculated including rate constant of the degradation of the studied
      antibiotic.

PMID- 29223056
TI  - Synthesis and fluorescence properties of some difluoroboron beta-diketonate
      complexes and composite containing PMMA.
AB  - A series of difluoroboron beta-diketonate complexes, containing the indon-beta
      diketonate ligand carrying methyl or methoxyl substituents was synthesized. The
      crystal structures of the complexes were confirmed by single crystal X-ray
      diffraction studies. The fluorescence properties of compounds were studied in
      solution state, solid state and on PMMA polymer matrix. The photophysical data of
      compounds 2a-2d exhibited strong fluorescence and photostability under the
      ultraviolet light (Hg lamp). The complex 2b showed higher fluorescence intensity
      in solution state as compared to other complexes of the series. The complexes 2c
      and 2d showed higher fluorescence intensity in the solid state, which are
      ascribed to the stronger pi-pi interactions between ligands in the solid state.
      The introduction of methoxyl or methyl groups on the benzene rings enhanced the
      absorption intensity, emission intensity, quantum yields and fluorescence
      lifetimes due to their electron-donating nature. Furthermore, the complex 2b was
      doped into the PMMA to produce hybrid materials, where the PMMA matrix acted as
      sensitizer for the central boron ion to enhance the fluorescence emission
      intensity and quantum yields.

PMID- 29223057
TI  - The ground and low-lying excited states and feasibility of laser cooling for GaH+
      and InH+ cations.
AB  - The potential energy curves and transition dipole moments of 12Sigma+ and 12Pi
      states of GaH+ and InH+ cations are performed by employing ab initio
      calculations. Based on the potential energy curves, the rotational and
      vibrational energy levels of the two states are obtained by solving the
      Schrodinger equation of nuclear movement. The spectroscopic parameters are
      deduced with the obtained rovibrational energy levels. The spin-orbit coupling
      effect of the 2Pi states for both the GaH+ and InH+ cations are also calculated.
      The feasibility of laser cooling of GaH+ and InH+ cations are examined by using
      the results of the electronic and spectroscopic properties. The highly diagonal
      Franck-Condon factors and appropriate radiative lifetimes are determined by using
      the potential energy curves and transition dipole moments for the 2Pi1/2, 3/2<
      >12Sigma+ transitions. The results indicate that the 2Pi1/2, 3/2<->12Sigma+
      transitions of both GaH+ and InH+ cations are appropriate for the close cycle
      transition of laser cooling. The optical scheme of the laser cooling is
      constructed for the GaH+ and InH+ cations.

PMID- 29223058
TI  - Discrimination of geographical origin and detection of adulteration of kudzu root
      by fluorescence spectroscopy coupled with multi-way pattern recognition.
AB  - In this work, fluorescence spectroscopy combined with multi-way pattern
      recognition techniques were developed for determining the geographical origin of
      kudzu root and detection and quantification of adulterants in kudzu root.
      Excitation-emission (EEM) spectra were obtained for 150 pure kudzu root samples
      of different geographical origins and 150 fake kudzu roots with different
      adulteration proportions by recording emission from 330 to 570nm with excitation
      in the range of 320-480nm, respectively. Multi-way principal components analysis
      (M-PCA) and multilinear partial least squares discriminant analysis (N-PLS-DA)
      methods were used to decompose the excitation-emission matrices datasets. 150
      pure kudzu root samples could be differentiated exactly from each other according
      to their geographical origins by M-PCA and N-PLS-DA models. For the adulteration
      kudzu root samples, N-PLS-DA got better and more reliable classification result
      comparing with the M-PCA model. The results obtained in this study indicated that
      EEM spectroscopy coupling with multi-way pattern recognition could be used as an
      easy, rapid and novel tool to distinguish the geographical origin of kudzu root
      and detect adulterated kudzu root. Besides, this method was also suitable for
      determining the geographic origin and detection the adulteration of the other
      foodstuffs which can produce fluorescence.

PMID- 29223059
TI  - A highly selective fluorescence sensing platform for nanomolar Hg(II) detection
      based on cytosine derived quantum dot.
AB  - Inspired by low toxicity and good biocompatibility of biomass derived quantum dot
      (QD), we herein developed a cytosine derived quantum dot, namely cyt-dot, via a
      one-step hydrothermal synthesis. The as-prepared cyt-dot emits blue fluorescence
      (FL) containing abundant oxygen (20.6at.%) and nitrogen (24.1at.%) contents. The
      cyt-dot based sensing platform shows exclusive selectivity for Hg(II) while being
      insensitive towards Fe(III) and Ag(I), which are important interference that
      usually cannot be ruled out. The detection limit for Hg(II) is of 11nM, which is
      very close to the guideline value of 10nM allowed by the U.S. Environmental
      Protection Agency in drinking water. In real water sample analyses, the present
      sensing platform can fulfil satisfied recoveries ranging from 100% to 108%.
      Besides, the acidity of solution has almost no effect on the sensing performance
      of the cyt-dot in a pH range of 5-8, suggesting its potential applications in
      sensing and bio-imaging.

PMID- 29223061
TI  - Impurity profiling of N,N'-ethylenebis-l-cysteine diethyl ester (Bicisate).
AB  - A HPLC-UV-CAD method with a HILIC column for impurity profiling of the 99mTc
      chelating agent bicisate has been developed and evaluated. Bicisate and its
      impurities were separated by means of isocratic elution on a zwitterionic
      stationary phase using a mixture of 7.5mmol/L trifluoroacetic acid and
      acetonitrile (47.5:52.5 V/V) as the mobile phase. Five different bicisate batches
      of a manufacturer were tested using the method. In addition LC-MS experiments
      were conducted in order to identify the impurities. The predominant impurities
      found were the oxidation product (disulfide), the monoester of ethylene
      dicysteine and an unknown compound with an m/z of 293 in ESI positive mode. A new
      degradation product of bicisate, bicisate lactam, was identified during sample
      solution stability assessment.

PMID- 29223060
TI  - Recent advances in lipid separations and structural elucidation using mass
      spectrometry combined with ion mobility spectrometry, ion-molecule reactions and
      fragmentation approaches.
AB  - Lipids are a vital class of molecules that play important and varied roles in
      biological processes, however, fully understanding these roles is extremely
      difficult due to the immense number and diversity of possible lipid species.
      While recent advances in chromatography and high resolution mass spectrometry
      have greatly progressed knowledge about distinct lipid species and functions,
      effectively separating many lipids still remains problematic. Isomeric lipids
      have made lipid characterization especially difficult and occur due to subclasses
      having the same chemical composition, or species having multiple acyl chain
      connectivities (sn-1, sn-2, or sn-3), double bond positions and orientations (cis
      or trans), and functional group stereochemistries (R versus S). To aid in isomer
      characterization, ion mobility spectrometry separations, ion-molecule reactions
      and fragmentation techniques have increasingly been added to lipid analysis
      workflows. In this manuscript, we review the current state of these approaches
      and their capabilities for improving the identification of lipid species.

PMID- 29223062
TI  - HPLC-MS/MS method optimisation for matrix metalloproteinase 3 and matrix
      metalloproteinase 9 determination in human blood serum using target analysis.
AB  - A quantitative analysis of zinc endopeptidases matrix metalloproteinase 9 (MMP9)
      and matrix metalloproteinase 3 (MMP3) from human blood serum are presented. Both
      matrix metalloproteinases (MMP) are present in human blood serum and can be used
      as biomarkers for different diseases. The analysis was performed using LC-MS/MS
      with a triple quadrupole mass spectrometer, based on two specific peptides of
      each MMP in comparison with an enzyme-linked immunosorbent assay (ELISA). While
      the conditions for the LC-MS/MS analysis of MMP9 peptides were previously
      reported for bronchoalveolar lavage fluid, the analysis of MMP3 peptides was
      newly quantified for human blood serum herein for the first time. For MMP3, the
      linear behaviour was determined in the concentration range from 1.0-200.0ng/mL
      (R2=0.997) with an LLOD of 0.5ng/mL. For MMP9, linearity was determined in the
      concentration range from 6.5-65.0ng/mL (R2=0.995) with an LLOD of 2.0ng/mL.

PMID- 29223063
TI  - Phytochemical study of the trunk bark of Citharexylum spinosum L. growing in
      Tunisia: Isolation and structure elucidation of iridoid glycosides.
AB  - A phytochemical investigation of the trunk bark ethyl acetate extract of
      Citharexylum spinosum L. has led to the isolation of four previously undescribed
      iridoid glycosides, tunispinosides A-D, and five known phenylethanoid glycosides,
      verbascoside, leucosceptoside A, martynoside, isoverbascoside and plantainoside
      C, together with 4-hydroxy-2,6-dimethoxyphenyl 6'-O-vanilloyl-beta-D
      glucopyranoside, two 8,3'-neolignan glycosides, plucheosides D1-D2, coniferyl
      aldehyde, vanillic acid, syringic acid, ferulic acid and tyrosol. All compounds
      were isolated for the first time from C. spinosum. Their isolation was carried
      out using silica gel column and high performance liquid chromatography (HPLC).
      Structures were established by spectroscopic means including 1D and 2D NMR
      experiments, and spectrometric ESI-HRMS analysis.

PMID- 29223064
TI  - Patient characteristics, incidence, technique, outcomes and early prediction of
      tracheostomy in the state of Victoria, Australia.
AB  - BACKGROUND: Tracheostomy is a relatively common procedure in Intensive Care Unit
      (ICU) patients. AIMS: To study the patient characteristics, incidence, technique,
      outcomes and prediction of tracheostomy in the State of Victoria, Australia.
      METHODS: We used data from the Australian and New Zealand Intensive Care Society
      Adult Patient Database (ANZICS APD) and the Victorian Admitted Episode Dataset
      (VAED) to identify and match patients who had received a tracheostomy from 2004
      to 2014. RESULTS: Between 1st January 2004 and 30th June 2014, 9750 patients
      received a tracheostomy with 7670 available for matching and 6010 (78.4%)
      successfully matched. Of the matched tracheostomy patients, median age was
      61years, median APACHE IIIJ score was 66 and overall hospital mortality was 21%.
      The incidence of tracheostomy almost halved over the decade with more than half
      of tracheostomies (53.5%) being percutaneous. Hospital mortality of patients
      receiving a tracheostomy decreased from 26.5% in 2004 to 16.5% in 2014 by an
      average decrease of 6%/year. No robust model could be developed to predict
      tracheostomy. CONCLUSION: The incidence of tracheostomy and the adjusted
      mortality rate of patients who received a tracheostomy have significantly
      decreased over a decade. Day of admission information could not be used to
      predict subsequent tracheostomy.

PMID- 29223065
TI  - Arabinogalactan proteins: Immunolocalization in the developing ovary of a
      facultative apomict Fragaria x ananassa (Duch.).
AB  - BACKGROUND AND AIMS: Arabinogalactan proteins are present in the extracellular
      matrix and their occurrence is developmentally regulated. The studies were
      carried out to localise arabinogalactan proteins in ovary cells of Fragaria x
      ananassa Duchesne (strawberry) during megasporogenesis, megagametogenesis, and
      formation of the embryo. METHODS: The research included studies of ovary
      histochemistry and immunofluorescence labelling of AGP epitopes was performed
      with antibodies JIM13, JIM15 and MAC207. The use of the immunogold labelling
      method allowed specific detection of AGP epitopes at the subcellular level. KEY
      RESULTS: The localization of AGPs was studied in the cells of the ovary wall and
      elements building the developing ovule i.e. the integument, nucellus, archespore,
      megaspores, embryo sac, and embryo of a facultative apomict Fragaria x ananassa
      cv. 'Mount Everest'. For the first time the presence of AGP epitopes at the stage
      of a multicellular archespore was described. The occurrence of AGPs in the
      functional megaspore walls is related to selection of a megaspore continuing
      development; during later stages of development, AGPs are also evident markers of
      the female gametophyte. The intense fluorescence indicates the presence of AGPs
      in the embryo sac wall as well as in the cytoplasm compartment of the egg
      apparatus and around the secondary nucleus of the central cell. The localization
      of AGPs in the ovule of F. x ananassa resembles the distribution of these
      proteins in amphimictic plants. CONCLUSIONS: Arabinogalactan proteins occur in
      similar parts of the ovule of amphimictic and apomictic plants. The results
      confirm the participation of AGPs in reproductive structures as a useful marker
      during development of female gametophyte.

PMID- 29223066
TI  - Overexpression of the maize E3 ubiquitin ligase gene ZmAIRP4 enhances drought
      stress tolerance in Arabidopsis.
AB  - Ubiquitin-mediated protein degradation plays a crucial role in enabling plants to
      effectively and efficiently cope with environmental stresses. The E3 ligases have
      emerged as a central component of the ubiquitination pathway and modulate plant
      response to abiotic stresses. However, few such studies have been reported in
      maize. In this study, a C3HC4-type RING finger E3 ligase in maize, ZmAIRP4 (Zea
      mays Abscisic acid [ABA]-Insensitive RING Protein 4), which is an ortholog of
      AtAIRP4, was isolated by reverse transcription polymerase chain reaction with
      specific primers, and its functions in tolerance to drought stress were
      described. ZmAIRP4 was upregulated by ABA, polyethylene glycol and sodium
      chloride. In vitro ubiquitination assays and subcellular localization indicated
      that ZmAIRP4 was an active E3 ligase predominantly localized in the cytoplasm and
      nucleus. Compared to wild type, ZmAIRP4-overexpressing Arabidopsis plants were
      hypersensitive to ABA during early seedling development, and showed enhanced
      drought tolerance. Moreover, the transcript levels of several drought-related
      downstream genes in transgenic plants were dramatically increased compared with
      wild type plants. Our results suggested that E3 ligase ZmAIRP4 is a positive
      regulator in the drought tolerance response pathway.

PMID- 29223067
TI  - Dissection of resistance to Microdochium nivale in Lolium multiflorum/Festuca
      arundinacea introgression forms.
AB  - The potential of resistance to Microdochium nivale is still not recognized for
      numerous plant species. The forage grasses of Lolium-Festuca complex are
      important for grass-biomass production in the temperate regions. Lolium
      multiflorum is a grass with a high forage quality and productivity but also a
      relatively low resistance to M. nivale. On the contrary, F. arundinacea has a
      higher potential of resistance but simultaneously a significantly lower forage
      quality. These two species cross with each other and the intergeneric hybrids
      possess complementary characters of both genera. Herein, for the first time, we
      perform the research on L. multiflorum/F. arundinacea introgression forms to
      decipher mechanisms of resistance to M. nivale in that group of plants. Two forms
      with distinct levels of resistance were used as models in cytogenetic and
      biochemical studies. The resistant plant was shown to be a tetraploid with 28 L.
      multiflorum chromosomes, including one with three F. arundinacea introgressions.
      The susceptible introgression form revealed the unbalanced genomic structure and
      only 25 chromosomes. Twenty four chromosomes were shown to be L. multiflorum
      chromosomes, including one chromosome with F. arundinacea segment. One Festuca
      chromosome with additional two interstitial F. arundinacea segments, was also
      revealed in the susceptible form. The selected introgression forms differed in
      the accumulation profiles of total soluble carbohydrates, phytohormones, and
      phenolics in the leaf and crown tissue under the control and infection
      conditions. The higher amount of carbohydrates and salicylic acid in the leaves
      and crowns as well as a lower amount of abscisic acid in both studied organs and
      jasmonic acid in the crowns, were shown to be crucial for the expression of
      resistance to M. nivale in the analyzed hybrids.

PMID- 29223068
TI  - Comprehensive analysis and transcript profiling of Arabidopsis thaliana and Oryza
      sativa catalase gene family suggests their specific roles in development and
      stress responses.
AB  - Stress induces the generation of Reactive Oxygen Species (ROS) that ultimately
      hampers the growth, development, and productivity of the plant. As an antioxidant
      enzyme, catalase converts hydrogen peroxide to water and keeps ROS level down to
      protect cells from stress-induced apoptosis. Here, a genome-wide analysis of
      catalase gene family has been performed in two model plants- Arabidopsis thaliana
      and Oryza sativa. Both Arabidopsis and rice has a small family of three and four
      genes, respectively; that code for seven proteins each. Detailed analysis of
      these members in terms of their structure, duplication, chromosomal position and
      proteins subcellular localization, as well as expression profiling under various
      developmental and environmental cues, was performed. Catalase proteins were
      mostly found to be localized in the cytoplasm, followed by peroxisome and
      mitochondria. Phylogenetically plant catalases showed strong divergence from
      their non-plant counterparts. Expression profiling revealed that AtCAT3 and
      OsCATA are the constitutively expressive member; while AtCAT2, OsCATA, and OsCATC
      are the stress-responsive members. Moreover, an altered level of total rice
      catalase enzyme activity and H2O2 level was observed under various abiotic stress
      conditions. This indicates the stress-responsive transcriptome as well as
      proteome alteration of catalase in the plant.

PMID- 29223069
TI  - Neuropsychological and clinical heterogeneity of cognitive impairment in patients
      with multiple system atrophy.
AB  - OBJECTIVE: We evaluated neuropsychological tests to compare cognitive impairment
      between two types of multiple system atrophy: predominant parkinsonism (MSA-P)
      and predominant cerebellar ataxia (MSA-C). PATIENTS AND METHODS: This cross
      sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten
      with MSA-P. Presence of motor symptoms was determined by using the Unified Rating
      MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health
      Survey (SF-36), Scales for Outcomes in Parkinson's disease Autonomic (SCOPA-AUT),
      Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory
      (BDI). Neuropsychological tests were used to evaluate general cognition, verbal
      and visual memory, working memory, constructional ability, visuospatial,
      language, and executive function. RESULTS: The median age of the patients was 62
      years, median disease duration was 3.5 years, and median education level was 10
      years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and
      median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the
      continuous data between the two MSA subtypes and observed that bodily pain
      reported in the quality of life questionnaire, SF-36, was worse in MSA-P
      (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA
      C than MSA-P (p<0.05). CONCLUSION: Our comparative study of cognitive impairment
      in MSA-P and MSA-C showed that both groups had impaired executive and
      visuospatial functions, while the attention deficit was predominant only in MSA
      C. These findings support the concept that cognitive deficit originates from
      striatofrontal dysfunction and cerebellar degeneration. Our study also suggests
      that cognitive impairment is relevant in MSA, and clinical neurologists should
      not neglect evaluation of these aspects in their daily clinical practice.

PMID- 29223070
TI  - Trusting others: shared reality in testimonial learning.
AB  - Much of early learning depends on others, and the transmission of testimony
      presents children with a range of opportunities to learn about and from other
      people. Much work has focused on children's ability to select or prefer
      particular sources of information based on various epistemic (e.g. accuracy,
      reliability, perceptual access, expertise) and moral (e.g. benevolence, group
      membership, honesty) characteristics. Understanding the mechanisms by which such
      selective preferences emerge has been couched primarily in frameworks that treat
      testimony as a source of inductive evidence, and that treat children's trust as
      an evidence-based inference. However, there are other distinct interpersonal
      considerations that support children's trust towards others, considerations that
      influence who children learn from as well as other practical decisions.
      Broadening our conception of trust and considering the interpersonal reasons we
      have to trust others can both strengthen our current understanding of the role
      that trust plays in children's learning and practical decisions as well as
      provide a more holistic picture of how children participate in a shared reality
      with their family, peers, and communities.

PMID- 29223071
TI  - Bioactive potential of silica coatings and its effect on the adhesion of proteins
      to titanium implants.
AB  - There is an ever-increasing need to develop dental implants with ideal
      characteristics to achieve specific and desired biological response in the scope
      of improve the healing process post-implantation. Following that premise,
      enhancing and optimizing titanium implants through superficial treatments, like
      silica sol-gel hybrid coatings, are regarded as a route of future research in
      this area. These coatings change the physicochemical properties of the implant,
      ultimately affecting its biological characteristics. Sandblasted acid-etched
      titanium (SAE-Ti) and a silica hybrid sol-gel coating (35M35G30T) applied onto
      the Ti substrate were examined. The results of in vitro and in vivo tests and the
      analysis of the protein layer adsorbed to each surface were compared and
      discussed. In vitro analysis with MC3T3-E1 osteoblastic cells, showed that the
      sol-gel coating raised the osteogenic activity potential of the implants (the
      expression of osteogenic markers, the alkaline phosphatase (ALP) and IL-6 mRNAs,
      increased). In the in vivo experiments using as model rabbit tibiae, both types
      of surfaces promoted osseointegration. However, the coated implants demonstrated
      a clear increase in the inflammatory activity in comparison with SAE-Ti. Mass
      spectrometry (LC-MS/MS) analysis showed differences in the composition of protein
      layers formed on the two tested surfaces. Large quantities of apolipoproteins
      were found attached predominantly to SAE-Ti. The 35M35G30T coating adsorbed a
      significant quantity of complement proteins, which might be related to the
      material intrinsic bioactivity, following an associated, natural and controlled
      immune response. The correlation between the proteomic data and the in vitro and
      in vivo outcomes is discussed on this experimental work.

PMID- 29223072
TI  - Alteration of autophagy-related proteins in peripheral blood mononuclear cells of
      patients with Parkinson's disease.
AB  - Previous postmortem studies demonstrated dysregulation of autophagy in patients
      with Parkinson's disease (PD). To clarify whether this alteration reflects a
      fundamental aspect of PD or represents the final stage of autophagy dysregulation
      resulting from a long neurodegenerative process, we focused on basal autophagy in
      peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls
      (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6
      core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg]
      2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6). Reverse transcription
      polymerase chain reaction and Western blot analysis confirmed significantly
      increased protein levels of upstream autophagy (ULK1, Beclin1, and
      autophagy/beclin1 regulator 1) with negative feedback of mRNA expression for
      these proteins in PD. These protein levels were correlated with increased levels
      of alpha-synuclein in PBMCs. The expression level of the oligomeric form of alpha
      synuclein in PBMCs paralleled the clinical severity of PD and the degeneration of
      cardiac sympathetic nerves. Basal activity of autophagy can be lower in patients
      with PD. Alteration of basal autophagy may be a fundamental aspect of PD.

PMID- 29223073
TI  - Evidence for pain attenuation by the motor system-based judgment of agency.
AB  - Pain is an integral part of our lives. Although the effect of 'control' on sensed
      pain has been extensively studied and discussed, recent findings seem to be at
      odds with the substantial evidence for a robust motor-based sensory attenuation
      effect - an indirect marker for one's sense of agency. The goal of the current
      study was to re-examine whether there is evidence for such an effect in the
      context of pain. In three experiments, human participants were aversively
      stimulated and the sensitivity of self-reported pain to factors previously shown
      to modulate the sensory attenuation effect was tested (control over parameters of
      the stimulation; temporal contiguity and predictability, and stimulation
      intensity). Two of three experiments found some evidence that objective control
      attenuates pain, but only when the painful stimulation immediately follows the
      motor response. We discuss the complex relations between having objective
      control, feeling helpless, predictability and sensed pain.

PMID- 29223074
TI  - Bioaccumulation and trophic transfer of cyclic volatile methylsiloxanes (cVMS) in
      the aquatic marine food webs of the Oslofjord, Norway.
AB  - The trophic transfer of cyclic methylsiloxanes (cVMS) in aquatic ecosystems is an
      important criterion for assessing bioaccumulation and ecological risk.
      Bioaccumulation and trophic transfer of cVMS, specifically
      octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and
      dodecamethylcyclohexasiloxane (D6), were evaluated for the marine food webs of
      the Inner and Outer Oslofjord, Norway. The sampled food webs included
      zooplankton, benthic macroinvertebrates, shellfish, and finfish species.
      Zooplankton, benthic macroinvertebrates, and shellfish occupied the lowest
      trophic levels (TL ~2 to 3); northern shrimp (Pandalus borealis) and Atlantic
      herring (Clupea harengus) occupied the middle trophic levels (TL ~3 to 4), and
      Atlantic cod (Gadus morhua) occupied the highest tropic level (TL>4.0). Trophic
      dynamics in the Oslofjord were best described as a compressed food web defined by
      demersal and pelagic components that were confounded by a diversity in prey
      organisms and feeding relationships. Lipid-normalized concentrations of D4, D5,
      and D6 were greatest in the lowest trophic levels and significantly decreased up
      the food web, with the lowest concentrations being observed in the highest
      trophic level species. Trophic magnification factors (TMF) for D4, D5, and D6
      were <1.0 (range 0.3 to 0.9) and were consistent between the Inner and Outer
      Oslofjord, indicating that exposure did not impact TMF across the marine food
      web. There was no evidence to suggest biomagnification of cVMS in the Oslofjord.
      Rather, results indicated that trophic dilution of cVMS, not trophic
      magnification, occurred across the sampled food webs.

PMID- 29223075
TI  - Mercury inputs and redistribution in the Penobscot River and estuary, Maine.
AB  - We examined total mercury (Hg) distributions in sediments from the Penobscot
      River and estuary, Maine, a site of extensive Hg releases from HoltraChem (1967
      2000). Our objectives were to quantify: (1) bottom sediment Hg inventories (upper
      ~1m; 50-100 y); (2) sediment accumulation rates; and (3) contemporary Hg fluxes
      to bottom sediments; by sampling the Penobscot River (PBR), Mendall Marsh (MM),
      the Orland River (OR) and the Penobscot estuary (ES). Hg was rapidly distributed
      here, and the cumulative total (9.28 metric tons) associated with sediments
      system-wide was within the range released (6-12 metric tons). Evidence of
      sediment/Hg remobilization was observed in cores primarily from the PBR, and to a
      lesser extent the ES, whereas cores from MM, most of the OR, the ES, and half
      from the PBR exhibited sharp peaks in Hg concentrations at depth, followed by
      gradual decreases towards the surface. Based on background PBR sediment Hg
      concentrations (100ngg-1), "elevated" (300ngg-1), or "highly elevated" (600ngg-1)
      Hg concentrations in sediments, and resulting inventories, we assessed impact
      levels ("elevated">=270, or "highly elevated">=540mgm-2). 71% of PBR stations had
      "elevated", and 29% had "highly elevated" Hg inventories; 45% of MM stations had
      "elevated", and 27% had "highly elevated" inventories; 80% of OR stations had
      "elevated" inventories only; and 17% of ES stations had "elevated" inventories
      only. Most "highly elevated" stations were located within 8km of HoltraChem, in
      MM, in the PBR, and in the OR. Near-surface sediments in the OR, PBR and MM were
      all "highly elevated", while those in the ES were "elevated", on average. Mean Hg
      fluxes to bottom sediments were greatest in the OR (554), followed by the PBR
      (469), then MM (452), and finally the ES (204ngcm-2y-1).

PMID- 29223076
TI  - The impact of soil erosion on soil fertility and vine vigor. A multidisciplinary
      approach based on field, laboratory and remote sensing approaches.
AB  - Soil erosion processes in vineyards, beyond surface runoff and sediment
      transport, have a strong effect on soil organic carbon (SOC) loss and
      redistribution along the slope. Variation in SOC across the landscape can
      determine differences in soil fertility and vine vigor. The goal of this research
      was to analyze the interactions among vines vigor, sediment delivery and SOC in a
      sloping vineyard located in Sicily. Six pedons were studied along the slope by
      digging 6 pits up to 60cm depth. Soil was sampled every 10cm and SOC, water
      extractable organic carbon (WEOC) and specific ultraviolet absorbance (SUVA) were
      analyzed. Erosion rates, detachment and deposition areas were measured by the
      pole height method which allowed mapping of the soil redistribution. The vigor of
      vegetation, expressed as Normalized Difference Vegetation Index (NDVI), derived
      from high-resolution satellite multispectral data, was compared with measured
      pruning weight. Results confirmed that soil erosion, sediment redistribution and
      SOC across the slope was strongly affected by topographic features, slope and
      curvature. The erosion rate was 16Mgha-1y-1 since the time of planting (6years).
      SOC redistribution was strongly correlated with the detachment or deposition
      areas as highlighted by pole height measurements. The off-farm SOC loss over six
      years amounted to 1.2MgCha-1. SUVA254 values, which indicate hydrophobic material
      rich in aromatic constituents of WEOC, decreased significantly along the slope,
      demonstrating that WEOC in the detachment site is more stable in comparison to
      deposition sites. The plant vigor was strongly correlated with WEOC constituents.
      Results demonstrated that high resolution passive remote sensing data combined
      with soil and plant analyses can survey areas with contrasting SOC, soil
      fertility, soil erosion and plant vigor. This will allow monitoring of soil
      erosion and degradation risk areas and support decision-makers in developing
      measures for friendly environmental management.

PMID- 29223077
TI  - Multiple linear regression based congener profile correlation to estimate the
      toxicity (TEQ) and dioxin concentration in atmospheric emissions.
AB  - The formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) is
      governed by complex chemical reactions with complex kinetic models. The
      simulation of Municipal Solid Waste incinerators, or other industrial thermal
      processes, is a powerful tool that can be used to optimize and control them, and
      reducing the number of components to simulate is mandatory for a proper use. In
      this study it has been determined that only the formation of 3 of the 17 main
      PCDD/F congeners can be considered as linearly independent. This fact has been
      used to establish linear regression models that are able to estimate properly the
      total amount and toxicity of a sample considering only the amount of 1,2,3,6,7,8
      HxCDD, OCDF and 2,3,7,8-TCDF. All models have been validated using new samples
      performing a close approach to the real values provided by complete analytical
      studies. The average relative error is 3.5% and the maximum relative error is
      below 9% for these new testing samples. The main goal of our investigation is to
      build a dynamic simulation process of a MSW facility and include the dioxins
      formation on it using these models.

PMID- 29223078
TI  - Impact on mortality of biomass combustion from wildfires in Spain: A regional
      analysis.
AB  - Studies that analyse the impact on mortality of particulate matter (PM) produced
      by biomass combustion from wildfires mostly focus on a single city or on cities
      in different countries, with very few concentrating on one country as a whole.
      Accordingly, the aim of this paper was to analyse the impact that PM has on daily
      mortality in Spain on days with biomass combustion from wildfires. To analyse
      natural PM advections the Ministry of Agriculture and Fishing, Food & Environment
      divides Spain into 9 geographical regions. One province representative of each
      region for was selected analysis purposes, with provincial daily natural-cause
      mortality across the period 2004-2009 as the dependent variable, and daily mean
      PM concentrations in the provincial capital as the independent variable. We
      controlled for the effect of other chemical pollutants (NO2 and O3), maximum
      daily temperature on heat-wave days, day of the week, trends, seasonalities and
      the autoregressive nature of the series, using generalised linear models with the
      Poisson regression link to calculate relative risks (RRs) and the increase in RR
      (IRR) of PM-related mortality. The analysis was performed for days with and
      without biomass advections (DBA and DNBA respectively), with a breakdown by year,
      summer, and the remainder of the year (i.e., excluding summer). The results
      indicated that daily mean PM concentrations were higher on DBA than on DNBA, with
      statistically significant differences in most provinces. Furthermore, PM10 was
      associated with higher daily mortality on DBA in regions where wildfires were
      most frequent, but not in the remaining provinces. This translated as an IRR per
      10MUg/m3 of PM of 7.93 (2.36-13.81) in the North-west, 3.76 (1.36-6.22) in the
      Centre and 4.46 (2.99-5.94) in the South-west, values which in all cases were
      statistically higher than those obtained on DNBA. The increase in PM caused by
      biomass advections from wildfires is linked to a significant IRR of mortality in
      Spain. Hence, the fact that wildfires are likely to become increasingly frequent
      in the context of climate change makes this type of analysis particularly
      necessary.

PMID- 29223079
TI  - Kaolinite adsorption-regeneration system for dyestuff treatment by Fenton based
      processes.
AB  - The regeneration and reuse of adsorbents is a subject of interest nowadays in
      order to reduce the pollution and the wastes generated in the adsorption
      wastewater treatment. In this work, the regeneration of the spent kaolinite by
      different advanced oxidation processes (Fenton, electro-Fenton and electrokinetic
      Fenton) was evaluated. Initially, it was confirmed the ability of a low cost
      clayey material, kaolinite, for the adsorption of model dye such as Rhodamine B
      showing Freundlich isotherm fitting. Then, the regeneration and consequent
      degradation of the pollutant in the adsorbent by Fenton based processes was
      carried out. The role of different parameters affecting the regeneration process
      (H2O2:Fe2+ ratio, liquid:solid ratio) were evaluated. Working at 100:1 H2O2:Fe2+
      ratio and 30min near complete dye removal (around 97%) from kaolinite was
      obtained by Fenton treatment. After that, a two-stage treatment for adsorption
      regeneration was evaluated during five treatment cycles demonstrating its
      viability for regeneration of the adsorbent through dye degradation. Based on the
      successful application of Fenton technique, the improvement of the treatment by
      electro-Fenton and electrokinetic-Fenton were studied for different solid:liquid
      ratios achieving satisfactory regeneration values.

PMID- 29223080
TI  - Glacial influence and stream macroinvertebrate biodiversity under climate change:
      Lessons from the Southern Alps.
AB  - The aim of this work was to highlight the main ecological predictors driving
      invertebrate distribution in eight glacier-fed streams in the Southern Alps.
      Thirty-five sites belonging to four stream types were sampled monthly during the
      ablation season of one, two or three years between 1996 and 2014. Taxa from
      glacial (kryal and glacio-rhithral) and non-glacial (kreno-rhithral and lake
      outlet) sites were separated by canonical correspondence analysis (CCA) along a
      glacial influence gradient and a hydrological-altitudinal gradient. High glacial
      influence was associated mainly with low maximum water temperature (Tmax), high
      Glacial Index (calculated as a function of glacier area and distance from the
      glacier), and the abundance of Diamesa species (D. steinboecki, D. goetghebueri,
      D. zernyi, and D. latitarsis). Change-point analysis and Threshold Indicator Taxa
      Analysis confirmed the CCA results in identifying these Diamesa species as the
      taxa with the strongest preference for high percent glacier cover in the
      catchment (change point~30%) and low Tmax (change point~6 degrees C). Temporal
      changes in community structure were highlighted in seven sites fed by glaciers
      under different retreat rates. Where the rate was faster and the remaining
      glacier smaller (?1km2), the most cold-stenothermal kryal inhabitant, D.
      steinboecki, almost disappeared or survived only as brachypterous populations,
      whereas other Diamesinae (Pseudokiefferiella parva), Orthocladiinae (e.g.
      Eukiefferiella, Orthocladius), Limoniidae, Baetidae, Nemouridae, and non-insect
      taxa (e.g. Oligochaeta, Hydracarina) became more abundant. Upstream migration was
      observed in Diamesa spp. which conquered new stream reaches left free by the
      retreating glacier, and euriecious taxa which colonized reaches with ameliorated
      environmental conditions, no longer the exclusive habitat of Diamesa spp. Co
      occurrence of stochastic and deterministic assembly processes seem to drive
      spatio-temporal changes in these invertebrate communities. Long-term ecological
      studies on the adaptive biology of kryal species will be useful to predict the
      fate of Alpine biodiversity.

PMID- 29223081
TI  - Dispersion of traffic derived air pollutants into urban parks.
AB  - Scarce land resources in dense cities means that small urban parks are important
      as a leisure and amenity resource for the urban population. However, streets with
      heavily traffic often surround these fragmented parks and increase the potential
      user exposure to air pollutants from vehicles. The dispersion profiles of PM2.5
      and black carbon from roadside into urban parks at pedestrian level, in Hong
      Kong, were measured using mobile high time resolution instruments. In the
      downwind direction, pollutant concentrations decreased rapidly from roadside and
      by some tens of metres reached relatively constant values. An even sharper
      gradient is found in the upwind direction, with a rapid increase detected within
      2m of the road edge. The distinct decay profiles were explained with an
      analytical dispersion model formulated based on the gradient transport theory
      using an Eulerian approach. The simulations using the dispersion model suggest
      17m as a typical halving distance under normal urban conditions, which is
      introduced to simplify the description of dispersion profiles. Using Hong Kong as
      an example, ~90% of urban parks, to different extent, overlap with the 17m
      halving distance from roads, which means few urban parks in Hong Kong avoid the
      impact from nearby traffic emissions. Thus, from the perspective of human
      exposure to air pollutants in urban parks, this study provides observations of
      relevance for future park design in dense cities.

PMID- 29223082
TI  - Deep rooted apple trees decrease groundwater recharge in the highland region of
      the Loess Plateau, China.
AB  - Unlike recharge in shallow rooted ecosystems, estimating the groundwater recharge
      beneath deep rooted plants that absorb water from deep soil remains difficult.
      The purpose of this research is to develop an approach to estimate the
      groundwater recharge beneath deep-rooted vegetation by combining water mass
      balance and chloride mass balance (CMB) and to quantify how the conversion of
      shallow-rooted cropland to deep-rooted apple orchards changes groundwater
      recharge. The proposed groundwater recharge rate under deep-rooted vegetation in
      this study is the difference between the groundwater recharge rate in a cropland
      (obtained using CMB) and the mean annual soil water storage deficit beneath an
      adjacent deep-rooted vegetation. The results show that the conversion from
      cropland (shallow-rooted) to apple orchard (deep-rooted) decreased soil water
      storage by 776, 1106, and 1117mm, corresponding to 19, 20, and 26-year-old apple
      orchards, respectively. Groundwater recharge beneath cropland, on average, was
      58mmyr-1, which amounts to 10% of the average annual precipitation. Groundwater
      recharge beneath the apple orchards were variable, but all being <3% of the
      average annual precipitation. The conversion of cropland to apple orchards lead
      to a substantial decrease in groundwater recharge, potentially threatening the
      sustainability of the land use change.

PMID- 29223083
TI  - Activity, toxicity, molecular docking, and environmental effects of three
      imidazolinone herbicides enantiomers.
AB  - All imidazolinone (IMI) herbicides are chiral consisting of two enantiomers;
      however, studies on the enantioselectivities of their interactions are limited.
      This study is a systematic assessment of the enantiomers and racemates of IMI
      herbicides, including semi-preparation and determination of absolute
      configurations, stereoselective bioactivity toward target organisms (Echinochloa
      crus-galli and Microcystis aeruginosa), and toxicity toward Michigan Cancer
      Foundation-7 (MCF-7) cells. R-imidazolinones were found to be more active than S
      IMIs in the inhibition of target organisms, and neither enantiomer had estrogenic
      activity. Moreover, the relationship between the molecular structures and the
      efficiency of target growth inhibition by the IMI herbicides was investigated.
      Molecular modeling provided the rational structural basis for the
      enantioselectivity of the acetohydroxyacid synthase (AHAS) activity of the IMIs.
      These findings encourage the application of enantiopure R-IMI herbicides to
      capitalize on their advantages over the racemates.

PMID- 29223084
TI  - Wetlands receiving water treated with coagulants improve water quality by
      removing dissolved organic carbon and disinfection byproduct precursors.
AB  - Constructed wetlands are used worldwide to improve water quality while also
      providing critical wetland habitat. However, wetlands have the potential to
      negatively impact drinking water quality by exporting dissolved organic carbon
      (DOC) that upon disinfection can form disinfection byproducts (DBPs) like
      trihalomethanes (THMs) and haloacetic acids (HAAs). We used a replicated field
      scale study located on organic rich soils in California's Sacramento-San Joaquin
      Delta to test whether constructed flow-through wetlands which receive water high
      in DOC that is treated with either iron- or aluminum-based coagulants can improve
      water quality with respect to DBP formation. Coagulation alone removed DOC (66
      77%) and THM (67-70%) precursors, and was even more effective at removing HAA
      precursors (77-90%). Passage of water through the wetlands increased DOC
      concentrations (1.5-7.5mgL-1), particularly during the warmer summer months,
      thereby reversing some of the benefits from coagulant addition. Despite this
      addition, water exiting the wetlands treated with coagulants had lower DOC and
      DBP precursor concentrations relative to untreated source water. Benefits of the
      coagulation-wetland systems were greatest during the winter months (approx. 50
      70% reduction in DOC and DBP precursor concentrations) when inflow water DOC
      concentrations were higher and wetland DOC production was lower. Optical
      properties suggest DOC in this system is predominantly comprised of high
      molecular weight, aromatic compounds, likely derived from degraded peat soils.

PMID- 29223085
TI  - Global platinum group element resources, reserves and mining - A critical
      assessment.
AB  - The platinum group elements (PGEs) are used in many technologies and products in
      modern society, especially auto-catalysts, chemical process catalysts and
      specialty alloys, yet supply is dominated by South Africa. This leads PGEs to be
      assessed as 'critical metals', signalling concern about the likelihood and
      consequences of social, environmental and economic impacts from disruptions to
      supply. In order to better understand the global PGE situation, this paper
      presents a comprehensive global assessment of PGE reserves and resources and the
      key mining trends which can affect supply. The data shows that global PGE
      resources have increased from 90,733t PGEs in 2010 to 105,682t PGEs in 2015, a
      16.4% increase - despite global production of 2243t PGEs over this period. This
      suggests that the key issues facing the PGE sector are not geological or resource
      depletion, but clearly social, economic and environmental in nature - as
      highlighted by recent social issues in South Africa and volatile global economic
      conditions. Concerns over PGE supply reliability and the implications of any
      supply disruption will therefore continue to see the PGEs labelled as critical
      metals - but certainly not due to resource depletion.

PMID- 29223086
TI  - Perceived versus actual water quality: Community studies in rural Oaxaca, Mexico.
AB  - Compromised water quality risks public health, which becomes particularly acute
      in economically marginalized communities. Although the majority of the clean
      water-deprived population resides in Sub-Saharan Africa and Asia, a significant
      portion (32 million) lives in Meso- and Latin-America. Oaxaca is one of the
      marginalized southern states of Mexico, which has experienced high morbidity from
      infectious diseases and also has suffered from a high rate of infant mortality.
      However, there has been a paucity of reports on the status of water quality of
      culturally diverse rural Oaxaca. This study follows community-based participatory
      research methods to address the data gap by reporting on water quality (chemical
      and microbiological) and by exploring social realities and water use practices
      within and among communities. Surveys and water quality analyses were conducted
      on 73 households in three rural communities, which were selected based on the
      choice of water sources (i.e., river water, groundwater, and spring water).
      Statistically significant variations among communities were observed including
      the sanitation infrastructure (p-value 0.001), public perception on water quality
      (p-value 0.007), and actual microbiological quality of water (p-value 0.001).
      Results indicate a high prevalence of diarrheal diseases, a desire to improve
      water quality and reduce the cost of water, and a need for education on water
      quality and health in all the surveyed communities. The complexities among the
      three studied communities highlight the need for undertaking appropriate policies
      and water treatment solutions.

PMID- 29223087
TI  - Oxidative stress in birds along a NOx and urbanisation gradient: An interspecific
      approach.
AB  - Urbanisation is regarded as one of the most threatening global issues for
      wildlife, however, measuring its impact is not always straight forward. Oxidative
      stress physiology has been suggested to be a useful biomarker of health and
      therefore, a potentially important indicator of the impact that urban
      environmental stressors, especially air pollution, can have on wildlife. For
      example, nitrogen oxides (NOx), released during incomplete combustion of fossil
      fuels, are highly potent pro-oxidants, thus predicted to affect either the
      protective antioxidants and/or cause oxidative damage to bio-molecules. To date,
      epidemiological modelling of the predicted association between oxidative stress
      and NOx exposure has not been performed in wild animals. Here, we address this
      short-coming, by investigating multiple oxidative stress markers in four common
      passerine bird species, the blue tit (Cyanistes caeruleus), great tit (Parus
      major), house sparrow (Passer domesticus) and tree sparrow (Passer montanus),
      living along a gradient of NOx and urbanisation levels in southern Sweden. First
      of all, the results revealed that long- and medium-term (one month and one week,
      respectively) NOx levels were highly correlated with the level of urbanisation.
      This confirms that the commonly used urbanisation index is a reliable proxy for
      urban air pollution. Furthermore, in accordance to our prediction, individuals
      exposed to higher long- and medium-term NOx levels/urbanisation had higher plasma
      antioxidant capacity. However, only tree sparrows showed higher oxidative damage
      (protein carbonyls) in relation to NOx levels and this association was absent
      with urbanisation. Lipid peroxidation, glutathione and superoxide dismutase
      levels did not co-vary with NOx/urbanisation. Given that most oxidative stress
      biomarkers showed strong species-specificity, independent of variation in
      NOx/urbanisation, the present study highlights the need to study variation in
      oxidative stress across contexts, seasons and life-stages in order to understand
      how the ecology and phylogeny of species interact to affect species resilience to
      urban environmental stress.

PMID- 29223088
TI  - Probing molecular interaction mechanisms of organic fouling on polyamide membrane
      using a surface forces apparatus: Implication for wastewater treatment.
AB  - Surface fouling is the dominant fouling mechanism of thin-film composite (TFC)
      membranes used in reverse osmosis (RO) technology. Understanding the complex
      interactions between foulant-membrane which drive the attachment and growth of
      foulants on membrane surface is of both fundamental and practical importance.
      This work aims to understand the molecular interaction mechanisms of organic
      fouling on RO-TFC membranes. A surface forces apparatus (SFA) was employed to
      directly measure the interaction forces and time-dependent adsorption behaviors
      between model organic foulants: humic acid (HA), bovine serum albumin (BSA), and
      lipopolysaccharides (LPS) and a polyamide (PA) thin film. PA thin film was
      prepared by interfacial condensation polymerization on mica substrates using m
      phenylenediamine and 1,3,5-benzenetricarbonyltrichloride. The interaction forces
      between PA films and different foulant (HA, BSA, LPS) were directly measured
      under controlled solution chemistries in an asymmetric configuration (foulant
      deposited PA films vs. PA films). The adsorption behaviors of these foulants on
      PA films were directly monitored in a symmetric configuration (PA films vs. PA
      films). These interactions were examined as a function of both contact time and
      solution chemistry (ionic strength). In asymmetrical configuration, both HA and
      BSA show repulsion with PA surface during approach and adhesion during
      separation, but LPS demonstrates repulsion only. In symmetrical configuration,
      all the foulants show adsorption on PA surface and the initial adsorption rate of
      foulant to PA surface follows the order of BSA>LPS>HA. The interaction mechanisms
      between PA films and foulants were discussed based on the interaction forces and
      interaction dynamics measurement.

PMID- 29223089
TI  - River water infiltration enhances denitrification efficiency in riparian
      groundwater.
AB  - Nitrate contamination in ground- and surface water is a persistent problem in
      countries with intense agriculture. The transition zone between rivers and their
      riparian aquifers, where river water and groundwater interact, may play an
      important role in mediating nitrate exports, as it can facilitate intensive
      denitrification, which permanently removes nitrate from the aquatic system.
      However, the in-situ factors controlling riparian denitrification are not fully
      understood, as they are often strongly linked and their effects superimpose each
      other. In this study, we present the evaluation of hydrochemical and isotopic
      data from a 2-year sampling period of river water and groundwater in the riparian
      zone along a 3rd order river in Central Germany. Based on bi- and multivariate
      statistics (Spearman's rank correlation and partial least squares regression) we
      can show, that highest rates for oxygen consumption and denitrification in the
      riparian aquifer occur where the fraction of infiltrated river water and at the
      same time groundwater temperature, are high. River discharge and depth to
      groundwater are additional explanatory variables for those reaction rates, but of
      minor importance. Our data and analyses suggest that at locations in the riparian
      aquifer, which show significant river water infiltration, heterotrophic microbial
      reactions in the riparian zone may be fueled by bioavailable organic carbon
      derived from the river water. We conclude that interactions between rivers and
      riparian groundwater are likely to be a key control of nitrate removal and should
      be considered as a measure to mitigate high nitrate exports from agricultural
      catchments.

PMID- 29223090
TI  - Oxidation of iopamidol with ferrate (Fe(VI)): Kinetics and formation of toxic
      iodinated disinfection by-products.
AB  - Presence of iodinated X-ray contrast media (ICMs) in source water is of high
      concern, because of their potential to form highly toxic iodinated disinfection
      by-products (I-DBPs). This study investigated kinetics, mechanisms and products
      for oxidation of one ICMs, iopamidol (IPM) by ferrate (Fe(VI)). The obtained
      apparent second-order rate constants for oxidation of IPM by Fe(VI) ranged from
      0.7 M-1 s-1 to 74.6 M-1 s-1 at pH 6.0-10.0, which were highly dependent on pH. It
      was found that the oxidation of IPM by Fe(VI) led to the formation of highly
      toxic I-DBPs. Iodoform (IF), iodoacetic acid and triiodoacetic acid formations
      were observed during the oxidation and IF dominated the formed I-DBPs. The
      formation of I-DBPs was also governed by pH and the maximum formation of I-DBPs
      occurred at pH 9.0. Transformation pathways of IPM by Fe(VI) oxidation were
      speculated to proceed through deiodination, amide hydrolysis and oxidation of
      amine reactions. The deiodination reaction during the oxidation of IPM by Fe(VI)
      contributed to the formation of I-DBPs. The formation of I-DBPs during the
      oxidation of IPM by Fe(VI) was significantly higher than those of iohexol,
      diatrizoate and iopromide, which was consistent with the lowest molecular orbital
      energy gap of IPM. Although Fe(VI) is considered as a green oxidant, the
      formation of highly toxic I-DBPs during the oxidation of IPM should receive great
      attention.

PMID- 29223091
TI  - Comparative analysis of vermicompost quality produced from rice straw and paper
      waste employing earthworm Eisenia fetida (Sav.).
AB  - Present study was undertaken to investigate the vermicomposting of two different
      organic wastes (rice straw and paper waste) employing, Eisenia fetida. Nine
      feedstocks were prepared with different ratios of wastes using cow dung as
      bulking substrate. After pre-composting, worms were allowed to feed on different
      feedstocks for 105 days under laboratory conditions. The results showed that NPK
      content was higher in the vermicompost. Heavy metal content was also higher in
      the vermicomposts. Whereas total organic carbon and C:N ratio were lower after
      vermicomposting, by 17.38-58.04% and 19-102% respectively. SEM images revealed
      changes in the morphology of vermicompost. Earthworm growth and reproduction was
      significant in different feedstocks except one containing 50% rice straw
      depicting that this ratio is not suitable for the earthworms. Results further
      demonstrated that proportion of bulking substrate affect the earthworm growth and
      reproduction.

PMID- 29223092
TI  - Treatment of dye wastewater using an ultrasonic aided nanoparticle stacked
      activated carbon: Kinetic and isotherm modelling.
AB  - The present work explains the biosorption of malachite green dye from aquatic
      systems by nano zero valent iron stacked activated carbon (NZVI-AC), which was
      prepared by dual surface modification strategy. NZVI-AC was characterized by
      using FTIR, SEM-EDX, XRD and TGA. NZVI-AC exhibited efficient performance in dye
      biosorption properties. Experimental variables such as time, pH, dye
      concentration, temperature and biosorbent dosage influenced Langmuir adsorption
      capacity of 187.3 mg/g. The present biosorption system was best described by
      pseudo-first order kinetics. The dye was completely knocked out of the solution
      within 60 min at equilibrium. The thermodynamic behaviour of NZVI-AC was
      exothermic, feasible and spontaneous. Experimental data was engaged to validate
      new solid-liquid phase equilibrium model, showing the average absolute relative
      deviation 7.72%. Hence the procedure was non-toxic, potential to retain
      biosorbent from the solution, applicable for multiple cycles. In context, NZVI-AC
      can be recommended for the treatment of dyes from industrial effluent.

PMID- 29223093
TI  - Combined SHARON and ANAMMOX processes for ammoniacal nitrogen stabilisation in
      landfill bioreactors.
AB  - Stabilisation of ammoniacal nitrogen from solid waste and leachate significantly
      improved by combining novel processes like SHARON (single reactor system for high
      activity ammonia removal over nitrite) and ANAMMOX (anaerobic ammonium oxidation)
      with advantages of lower carbon requirements, aeration and N2O emissions. This
      paper deals with establishing combined SHARON-ANAMMOX processes in situ pilot
      scale landfill bioreactors (LFBR). Molecular analysis in LFBR with changes in
      nitrogen, hydrazine, hydroxylamine confirmed aerobic and anaerobic ammonium
      oxidising bacteria (AOB & ANAMMOX) as key players in SHARON-ANAMMOX processes. In
      situ SHARON-ANAMMOX process was established in LFBR with total nitrogen and
      ammoniacal nitrogen removal efficiency of 84% and 71%, respectively at NLR of 1.2
      kgN/m3/d in 147 d, compared to ammoniacal nitrogen removal of 49% at NLR of 1.0
      kgNH4-N/m3/d in 336 d feasible in Control LFBR. Nitrogen massbalance demonstrated
      in situ SHARON-ANAMMOX advantageous than control LFBR with higher nitrogen
      transformation to N2 (50.8%) and lower residual nitrogen in solid waste (7.7%).

PMID- 29223094
TI  - Characterization of cellulase from Aspergillus tubingensis NKBP-55 for generation
      of fermentable sugars from agricultural residues.
AB  - The aim of this work was to characterize cellulase from Aspergillus tubingensis
      NKBP-55 for generation of fermentable sugars from agricultural residues. The
      strain produced high titres of cellulase (750 U/gds) on copra meal in solid state
      fermentation (SSF). The enzyme preparation also showed hemicellulolytic
      activities (U/gds) viz. endo-mannanase (1023), endo-xylanase (167), beta
      glucosidase (72) and alpha-galactosidase (54). Zymography revealed presence of
      six cellulases, six mannanases and one beta-glucosidase. It effectively degraded
      sugarcane bagasse (SCB) and rice straw (RS) releasing xylose, glucose and
      cellobiose. One cellulase (Cat 1, Mr ~65 kDa) was purified and characterized. It
      retained more than 50% activity at 70  degrees C after 150 mins and its activity
      was enhanced in the presence of Mn2+ ions (130%) and beta-mercaptoethanol (140%).
      FTIR and 13C CP/MAS NMR analysis of the enzyme treated SCB and RS revealed
      degradation of cellulose and hemicellulose, while 1H and 13C liquid state NMR
      experiments confirmed release of glucose.

PMID- 29223095
TI  - High-solid anaerobic digestion of corn straw for methane production and
      pretreatment of bio-briquette.
AB  - In this study, an integrated process was developed to produce methane and high
      quality bio-briquette (BB) using corn straw (CS) through high-solid anaerobic
      digestion (HS-AD). CS was anaerobic digested by using a leach bed reactor at four
      leachate recirculation strategies. After digesting for 28 days, highest methane
      yield of 179.6 mL/g-VS, which was corresponded to energy production of 5.55 MJ/kg
      CS, was obtained at a higher initial recirculation rate of 32 L-leachate per day.
      Compared with bio-briquette manufactured from raw CS and lignite, the
      compressive, immersion and falling strength properties of bio-briquette made from
      AD-treated CS (solid digestate) and lignite were significantly improved. A
      preferred BB can be obtained with side compressive strength of 863.8 +/- 10.8 N
      and calorific value of 20.21 MJ/kg-BB. The finding of this study indicated that
      the integrated process could be an alternative way to produce methane and high
      quality BB with CS.

PMID- 29223096
TI  - Discovery of aliphatic-chain hydroxamates containing indole derivatives with
      potent class I histone deacetylase inhibitory activities.
AB  - Histone deacetylase (HDAC) is a validated drug target for various diseases. This
      study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor
      used to treat cutaneous T-cell lymphoma (CTCL). The structure activity
      relationship of the resulting compounds that inhibited HDAC was disclosed as
      well. Some compounds exhibited much stronger inhibitory activities than SAHA. We
      identified two meta-series compounds 6j and 6k with a two-carbon linker had IC50
      values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented
      compounds with longer carbon chain linkers showed weaker inhibition. The result
      suggests that the linker chain length greatly contributed to enzyme inhibitory
      potency. In addition, comparison of enzyme-inhibiting activity between the
      compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting
      activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure
      analysis revealed structural differences with the inhibitor cap and metal-binding
      regions between the HDAC isozymes that affect interactions with the inhibitors
      and play a key role for selectivity. Further biological evaluation showed
      multiple cellular effects associated with compounds 6j- and 6k-induced HDAC
      inhibitory activity.

PMID- 29223097
TI  - Recent advances in microtubule-stabilizing agents.
AB  - Highly dynamic mitotic spindle microtubules are superb therapeutic targets for a
      group of chemically diverse and clinically successful anticancer drugs.
      Microtubule-targeted drugs disrupt microtubule dynamics in distinct ways, and
      they are primarily classified into two groups: microtubule destabilizing agents
      (MDAs), such as vinblastine, colchicine, and combretastatin-A4, and microtubule
      stabilizing agents (MSAs), such as paclitaxel and epothilones. Systematic
      discovery and development of new MSAs have been aided by extensive research on
      paclitaxel, yielding a large number of promising anticancer compounds. This
      review focuses on the natural sources, structural features, mechanisms of action,
      structure-activity relationship (SAR) and chemical synthesis of MSAs. These MSAs
      mainly include paclitaxel, taccalonolides, epothilones, FR182877 (cyclostreptin),
      dictyostatin, discodermolide, eleutherobin and sarcodictyins, zampanolide,
      dactylolide, laulimalides, peloruside and ceratamines from natural sources, as
      well as small molecular microtubule stabilizers obtained via chemical synthesis.
      Then we discuss the application prospect and development of these anticancer
      compounds.

PMID- 29223098
TI  - Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological
      evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti
      proliferative agents.
AB  - Barbituric and thiobarbituric acid derivatives have become progressively
      attractive to medicinal chemists due to their wide range of biological
      activities. Herein, different series of 1,3,5-trisubstituted barbiturates and
      thiobarbiturates were prepared in moderate to excellent yields and their activity
      as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti
      proliferative compounds was evaluated in vitro. Interesting bioactive
      barbiturates were found namely, 1,3-dimethyl-5-[1-(2
      phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3
      dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)
      trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50
      values of 24.3 and 27.9 MUM, respectively), and 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 MUM,
      respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine
      2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an
      IC50 value of 20.4 MUM. Moreover, relevant cytotoxicity against MCF-7 cells (IC50
      = 13.3 MUM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2
      thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5
      hydrazinylethylidenepyrimidines revealed antibacterial activity against
      Acinetobacter baumannii (MIC values between 12.5 and 25.0 MUM) which paves the
      way for developing new treatments for infections caused by this Gram-negative
      coccobacillus bacterium, known to be an opportunistic pathogen in humans with
      high relevance in multidrug-resistant nosocomial infections. The most promising
      bioactive barbiturates were studied in silico with emphasis on compliance with
      the Lipinski's rule of five as well as several pharmacokinetics and toxicity
      parameters.

PMID- 29223099
TI  - Nontoxic combretafuranone analogues with high in vitro antibacterial activity.
AB  - A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4
      and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was
      prepared. Cytotoxic effects on a panel of cancer and normal cell lines and
      antiinfective activity were evaluated, and the data were complemented with tests
      for the activation of caspase 3 and 7. High cytotoxicity was observed in some of
      the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5
      dihydrofuran-2-one with IC50 0.12-0.23 MUM, but the compounds were also highly
      toxic against non-malignant control cells. More importantly, notable
      antibacterial activity indicating G+ selectivity has been found in the 3,4
      diarylfuranone class of compounds for the first time. Hydroxymethylation of
      furanone C5 knocked out cytotoxic effects (up to 40 MUM) while maintaining
      significant activity against Staphylococcus strains in some derivatives. MIC95 of
      the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4
      methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98
      MUM (0.38 MUg/mL) and 3.9 MUM (1.52 MUg/mL) after 24 and 48 h, respectively.

PMID- 29223100
TI  - Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.
AB  - Inflammation and oxidative stress are common in many chronic diseases. Targeting
      signaling pathways that contribute to these conditions may have therapeutic
      potential. The transcription factor Nrf2 is a major regulator of phase II
      detoxification and anti-oxidant genes as well as anti-inflammatory and
      neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an
      important regulator of brain inflammation. The natural product curcumin exhibits
      numerous biological activities including ability to induce the expression of Nrf2
      dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a
      number of clinical studies with limited success, mainly owing to limited
      bioavailability and rapid metabolism. Enone analogues of curcumin were examined
      with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated
      into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon
      enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of
      Nrf2 were found in all three groups, many of which were more active than
      curcumin. Dose-response studies demonstrated that a range of substituents on the
      aromatic rings of these enones influenced not only the sensitivity to activation,
      reflected in EC50 values, but also the extent of activation, which suggests that
      multiple mechanisms are involved in the activation of Nrf2 by these analogues.

PMID- 29223101
TI  - Cognitive impairment measured by event-related potentials during early and late
      postoperative period following intravenous or inhalation anaesthesia.
AB  - OBJECTIVE: This study investigated modification in cognitive function following
      inhalation (IA) and total intravenous (TIVA) anaesthesia measured using auditory
      ERPs (Event Related Potentials). METHODS: Auditory ERPs examination with N1, P3a
      and P3b component registration was carried out one day before surgery (D-1) and
      on the first (D+1), sixth (D+6) and 42nd (D+42) days after surgery. Results were
      compared between two anaesthetic groups. RESULTS: On D+1, N1 latency was
      increased in the IA group. A significant reduction was observed in amplitude of
      the P3a component on D+6, which persisted up to D+42 for both IA and TIVA groups.
      A reduction in the amplitude of P3b on D+1 with normalization by D+6 was found in
      both groups as well. CONCLUSIONS: Intravenous and inhalation anaesthesia lead to
      similar changes in cognitive function as determined by ERPs, both during the
      early and late postoperative periods. It cannot be clearly confirmed whether the
      observed effects are due to anaesthesia or other unmonitored perioperative
      factors. SIGNIFICANCE: Post anaesthetic changes represent a subclinical
      impairment; nevertheless, they represent a potential risk for subsequent
      development of cognitive difficulties.

PMID- 29223102
TI  - Diagnosing Kernohan-Woltman notch phenomenon by somatosensory evoked potentials
      in intensive care unit.

PMID- 29223103
TI  - Bilateral early activity in the hip flexors associated with falls in stroke
      survivors: Preliminary evidence from laboratory-induced falls.
AB  - OBJECTIVE: Falls are the most common and expensive medical complication following
      stroke. Hypermetric reflexes have been suggested to impact post-stroke balance
      but no study has evaluated reflex amplitudes under real conditions of falls in
      this population. Our objective was to quantify the early reflexive responses
      during falls induced in the laboratory. METHODS: Sixteen stroke survivors were
      exposed to posteriorly directed treadmill perturbations that required a forward
      step to maintain a balance. Perturbations differed in terms of treadmill
      translation displacement, velocity, and acceleration. EMG amplitudes were
      compared between Fall/Recovery trials, as well as Fallers/Non-Fallers at two
      different time windows: 50-75 and 75-100 ms. RESULTS: Sixteen of 86 trials
      resulted in falls by nine subjects (Fallers). While no differences were found
      between 50 and 75 ms, EMG amplitude in the paretic rectus femoris muscle was
      larger between 75 and 100 ms during Fall trials. Further, a bilateral increase in
      RF activity was seen in Fallers but not Non-Fallers. Interestingly, the bilateral
      increase was related to perturbation intensity (larger EMG activity with larger
      perturbations) in Fallers, but again not in Non-Fallers. CONCLUSIONS: Heightened
      early recovery hip flexor activity between 75 and 100 ms is associated with falls
      and Fallers post-stroke. SIGNIFICANCE: Though requiring replication and expanded
      subject pools, these preliminary results reflect a possible clinically meaningful
      relationship between heightened reflexive responses and fall risk. Future work
      should evaluate the underlying mechanisms driving these heightened reflexes (e.g.
      stretch, startle) such that future rehabilitation techniques can address this
      abnormal response.

PMID- 29223104
TI  - Improvement of relative survival in elderly patients with acute myeloid leukaemia
      emerging from population-based cancer registries in Switzerland between 2001 and
      2013.
AB  - Acute Myeloid Leukaemia (AML) is a rare and heterogeneous haematological
      malignancy with increasing incidence in the elderly. We performed a population
      based, observational analysis of AML cases reported to the Cantonal Cancer
      Registries in Switzerland. Data was aggregated by the National Institute for
      Epidemiology and Cancer Registration and stratified for the two time periods 2001
      2007 and 2008-2013. Overall, 2351 new AML cases were registered with a stable age
      standardised incidence rate (3.0 [95 CI: 2.8-3.2] per 100,000 person-years). This
      indicates that our observed raise of annual AML cases (+10.9%) is mainly related
      to demographic ageing and not to an increase of age-specific risks. The fraction
      of non-classifiable AML cases decreased over time (54.6% to 41.8%) but remained
      high in elderly patients (65-74yrs: 44%; 75-84yrs: 54.2%, 85+yrs: 59.1%),
      suggesting less accurate diagnostics and reporting with increasing age. 5yrs
      relative survival (RS) correlated with AML risk class (favorable: 61.7%-68.4%;
      adverse risk: 11.4%-21.9%) and age (<65yrs: 42.6-43.3%; 75-84yrs: 2.0-3.0%), but
      improved only modestly overall (19.2% to 23.3%). Interestingly, we identified a
      significant improvement of RS in patients aged 65-74yrs (5yrs: 5.2% to 13.5%;
      p<0.001). As surrogate for changes in management, we found an increase of
      allogeneic haematopoietic stem cell transplantations (1.4 to 7%) and clinical
      trial activities (25 to 29%) for elderly AML patients during the observation
      period. Our analysis indicates that recent progress made in management of elderly
      AML patients results in an improvement of survival on a population-based level in
      Switzerland and that therapeutic nihilism is not justifiable.

PMID- 29223105
TI  - Towards a rapid assessment protocol for identifying pit lakes worthy of
      restoration.
AB  - Before the introduction of reclamation legislation in South Africa, final cut
      lakes in mining areas were left without any restoration while the final
      excavation was not back filled. Characteristics of these lacustrine water bodies
      vary considerably, but they are often linear in shape, large (1-30 ha), deep (2
      30 m) and have poorly developed littoral zones. With water tables often near the
      surface; a variety of vascular hydrophytes can colonize these bodies, thus
      establishing emerging wetland type ecosystems. These, man-made aquatic structures
      that are (unintentionally) created potentially offers some realistic and
      inexpensive mitigation options for some of the negative impacts associated with
      mining, i.e. these water bodies can become useful by yielding potentially
      valuable services. However, no method currently exists to compare and rank these
      water bodies according ecological integrity and the expected monetary value to be
      derived from them in order to select sites for restoration. To answer this need,
      we applied an index to determine the ability of these water bodies to provide
      useful services in their current state. The index was then used to derive
      estimates of the monetary value of potential services in order to allow
      comparison with the cost of restoring the water body in question or to compare
      with other pit lakes. We present a South African case study to illustrate the
      method. As far as could be established, this is the first attempt towards
      creating a rapid assessment tool as standardised way of comparing pit lakes that
      allows for the ranking and identification of those pit lakes worthy of
      restoration.

PMID- 29223106
TI  - Mechanochemical conversion of chrysotile/K2HPO4 mixtures into potential
      sustainable and environmentally friendly slow-release fertilizers.
AB  - Chrysotile fibers pose a threat to public health due to their association
      relation to respiratory malignant lung disease such as cancer. For this reason,
      they must be stored and discarded appropriately, including after treatment, which
      raises costs. In the present study, insoluble chrysotile fibers were milled in
      solid state with highly soluble K2HPO4, destroying both structures, making the
      chrysotile nontoxic and generating a new material with potential use as
      sustainable slow-release fertilizer (SSRF) containing mainly K and P. Based on
      the mills, milling conditions and chrysotile/K2HPO4 molar ratios used, Mg
      originating from chrysotile fibers reacted with K and P from dibasic potassium
      phosphate and were transformed into MgKPO4.H2O, MgKPO4.6H2O and probably a
      mixture of amorphous SiO2/MgO. In this study, a zirconia planetary mill and high
      energy ball mill were used, both of them produced SSRF. In conclusion, it was
      possible to synthesize high-value and extremely useful materials for agriculture
      using a harmful waste. The release rate can be tailored by controlling
      chrysotile/K2HPO4 molar ratios, grinding speed and time, which makes the process
      even more promising for farming applications.

PMID- 29223107
TI  - Recreation economics to inform migratory species conservation: Case study of the
      northern pintail.
AB  - Quantification of the economic value provided by migratory species can aid in
      targeting management efforts and funding to locations yielding the greatest
      benefits to society and species conservation. Here we illustrate a key step in
      this process by estimating hunting and birding values of the northern pintail
      (Anas acuta) within primary breeding and wintering habitats used during the
      species' annual migratory cycle in North America. We used published information
      on user expenditures and net economic values (consumer surplus) for recreational
      viewing and hunting to determine the economic value of pintail-based recreation
      in three primary breeding areas and two primary wintering areas. Summed
      expenditures and consumer surplus for northern pintail viewing were annually
      valued at $70M, and annual sport hunting totaled $31M (2014 USD). Expenditures
      for viewing ($42M) were more than twice as high than those for hunting ($18M).
      Estimates of consumer surplus, defined as the amount consumers are willing to pay
      above their current expenditures, were $15M greater for viewing ($28M) than for
      hunting ($13M). We discovered substantial annual consumer surplus ($41M)
      available for pintail conservation from birders and hunters. We also found
      spatial differences in economic value among the primary regions used by pintails,
      with viewing generally valued more in breeding regions than in wintering regions
      and the reverse being true for hunting. The economic value of pintail-based
      recreation in the Western wintering region ($26M) exceeded that in any other
      region by at least a factor of three. Our approach of developing regionally
      explicit economic values can be extended to other taxonomic groups, and is
      particularly suitable for migratory game birds because of the availability of
      large amounts of data. When combined with habitat-linked population models,
      regionally explicit values could inform development of more effective
      conservation finance and policy mechanisms to enhance environmental management
      and societal benefits across the geographically dispersed areas used by migratory
      species.

PMID- 29223108
TI  - Impacts of sugarcane agriculture expansion over low-intensity cattle ranch
      pasture in Brazil on greenhouse gases.
AB  - Sugarcane is a widespread bioenergy crop in tropical regions, and the growing
      global demand for renewable energy in recent years has led to a dramatic
      expansion and intensification of sugarcane agriculture in Brazil. Currently,
      extensive areas of low-intensity pasture are being converted to sugarcane, while
      management in the remaining pasture is becoming more intensive, i.e., includes
      tilling and fertilizer use. In this study, we assessed how such changes in land
      use and management practices alter emissions of greenhouse gases (GHG) such as
      CO2, N2O and CH4 by measuring in situ fluxes for one year after conversion from
      low-intensity pasture to conventional sugarcane agriculture and management
      intensive pasture. Results show that CO2 and N2O fluxes increased significantly
      in pasture and sugarcane with tillage, fertilizer use, or both combined.
      Emissions were highly variable for all GHGs, yet, cumulatively, it was clear that
      annual emissions in CO2-equivalent (CO2-eq) were higher in management-intense
      pasture and sugarcane than in unmanaged pasture. Surprisingly, tilled pasture
      with fertilizer (management-intensive pasture) resulted in higher CO2-eq
      emissions than conventional sugarcane. We concluded that intensification of
      pasture management and the conversion of pasture to sugarcane can increase the
      emission factor (EF) estimated for sugarcane produced in Brazil. The role of
      management practices and environmental conditions and the potential for reducing
      emissions are discussed.

PMID- 29223109
TI  - Genome-Wide Analysis of Barrett's Adenocarcinoma. A First Step Towards
      Identifying Patients at Risk and Developing Therapeutic Paths.
AB  - BACKGROUND: Barrett's esophagus metaplasia is the key precursor lesion of
      esophageal adenocarcinoma. The aim of this study was to find a subset of markers
      that may allow the identification of patients at risk for esophageal
      adenocarcinoma, and to determine genes differentially expressed in esophageal
      squamous cell carcinoma. METHODS: Laser capture microdissection technique was
      applied to procure cells from defined regions. Genome-wide RNA profiling was
      performed on esophageal adenocarcinoma (n = 21), Barrett's esophagus (n = 20),
      esophageal squamous carcinoma (n = 9) and healthy esophageal biopsies (n = 18)
      using the Affymetrix Human Genome U133plus 2.0 array. Microarray results were
      validated by quantitative real-time polymerase chain reaction in a second and
      independent cohort and by immunohistochemistry of two putative markers in a third
      independent cohort. RESULTS: Through unsupervised hierarchical clustering and
      principal component analysis, samples were separated into four distinct groups
      that match perfectly with histology. Many genes down-regulated in esophageal
      cancers belong to the epidermal differentiation complex or the related GO-group
      "cornified envelope" of terminally differentiated keratinocytes. Similarly,
      retinol metabolism was strongly down-regulated. Genes showing strong
      overexpression in esophageal carcinomas belong to the GO groups extracellular
      region /matrix such as MMP1, CTHRC1, and INHBA. According to an analysis of genes
      strongly up-regulated in both esophageal adenocarcinoma and Barrett's esophagus,
      REG4 might be of particular interest as an early marker for esophageal
      adenocarcinoma. CONCLUSIONS: Our study provides high quality data, which could
      serve for identification of potential biomarkers of Barrett's esophagus at risk
      of esophageal adenocarcinoma progression.

PMID- 29223110
TI  - Systemic inflammatory markers associated with cardiovascular disease and acute
      and chronic exposure to fine particulate matter air pollution (PM2.5) among US
      NHANES adults with metabolic syndrome.
AB  - BACKGROUND: There has been no investigation to date of adults with metabolic
      syndrome examining the association of short and long-term exposure to fine
      particulate matter (PM2.5) air pollution with cardiovascular-disease related
      inflammatory marker (WBC and CRP) levels in a nationally representative sample.
      The goal of this study is to assess the susceptibility of adults with metabolic
      syndrome to PM2.5 exposure as suggested by increased cardiovascular-disease
      related inflammatory marker levels. METHODS: A cross sectional analysis of adult
      National Health and Nutrition Examination Survey (NHANES) participants (2000
      2008) was carried out with linkage of CDC WONDER meteorological data and
      downscaler modeled USEPA air pollution data for census tracts in the continental
      United States. Participants were non-pregnant NHANES adults (2000-2008) with
      complete data for evaluating presence of metabolic syndrome and laboratory data
      on WBC and CRP. Exposures studied included short (lags 0-3 days and their
      averages), long-term (30 and 60 day moving and annual averages) PM2.5 exposure
      levels at the census tract level in the continental United States. The main
      outcomes included CRP and WBC levels the day of NHANES study visit analyzed using
      multiple linear regression, adjusting for age, gender, race, education, smoking
      status, history of any cardiovascular disease, maximum apparent temperature and
      ozone level, for participants with and without metabolic syndrome. RESULTS: A
      total of 7134 NHANES participants (35% with metabolic syndrome) met the inclusion
      criteria. After adjusting for confounders, we observed a significant effect of
      PM2.5 acutely at lag day 0 on CRP level; a 10ug/m3 rise in lag day 0 PM2.5 level
      was associated with a 10.1% increase (95% CI: 2.2-18.6%) in CRP levels for
      participants with metabolic syndrome. For those without metabolic syndrome, the
      change in CRP was -1.3% (95% CI -8.8%, 6.8%). There were no significant
      associations for WBC count. In this first national study of the effect of PM2.5
      air pollution on levels of cardiovascular-disease related inflammatory markers in
      adults with metabolic syndrome, CRP levels were found to be significantly
      increased in those with this condition with increased fine particulate matter
      levels at lag day 0. With one third of US adults with metabolic syndrome, the
      health impact of PM2.5 in this sensitive population may be significant.

PMID- 29223111
TI  - Consumer response to health and environmental sustainability information
      regarding seafood consumption.
AB  - Seafood consumption has an impact on both consumers' health and on the marine
      environment, making the integration of health and sustainability aspects in
      information and recommendation messages for consumers highly topical. This study
      presents the results of a consumer study in terms of the impact of exposure to a
      message about health and sustainability aspects of seafood on 986 participants
      from Belgium and Portugal. Possible drivers for behavioural change regarding
      seafood consumption frequency and sustainable seafood buying frequency are
      studied following exposure to the message. Initial behaviour emerges as the most
      important factor triggering a change in the intention to consume seafood twice
      per week and a change in the intention to buy sustainable seafood. A higher
      health benefit perception resulted in an increased intention to consume seafood
      twice per week. Attitude towards the message and the option to optimise
      consumers' choice of seafood species favouring sustainability were significant
      determinants of change in the intention to buy sustainable seafood. Different
      stakeholders may take the results of this communication strategy into account
      and, consequently, contribute to a seafood supply and related communication that
      supports public health and the marine environment.

PMID- 29223112
TI  - Development of the Handwriting Legibility Scale (HLS): A preliminary examination
      of Reliability and Validity.
AB  - BACKGROUND: Demands for the production of legible handwriting produced in a
      timely manner increase as children progress through school. Despite the
      considerable number of children faced with handwriting difficulties, there is no
      quick and practical tool to assess legibility in this population. AIM: The aim of
      this study was to develop the Handwriting Legibility Scale (HLS) and to establish
      the scale's reliability and validity. METHODS: The HLS is a non-language
      dependent scale which assesses global legibility, based on five criteria applied
      to samples of 'free writing'. Content validity, inter-rater reliability and
      internal consistency were initially examined using scripts from 20 children aged
      8-14 years. Construct validity was established by Principal Component Analysis
      (PCA) of data from 150 school children aged 9-14 years, with an additional
      examination of gender effects. Discriminant validity of the HLS score was
      examined in 29 children with Developmental Coordination Disorder (DCD) and 29
      typically developing (TD) children. RESULTS: The results indicated high internal
      consistency (alpha=0.92). The inter-rater reliability was acceptable but
      indicates the need to refine the scoring instructions. PCA of the five components
      revealed a one factor solution explaining 61% of the variance. In the
      discriminant analysis, 86.2% of the children with DCD and 89.7% of the TD
      children were correctly classified to their groups based on the total HLS score.
      CONCLUSIONS: The overall findings suggest that the HLS may be a useful tool to
      identify poor handwriting legibility, with application across different languages
      and writing scripts.

PMID- 29223113
TI  - Comparisons of severity classification systems for oropharyngeal dysfunction in
      children with cerebral palsy: Relations with other functional profiles.
AB  - This study aimed to investigate the relationships between various classification
      systems assessing the severity of oropharyngeal dysphagia and communication
      function and other functional profiles in children with cerebral palsy (CP). This
      is a prospective, cross-sectional, study in a university-affiliated, tertiary
      care hospital. We recruited 151 children with CP (mean age 6.11 years, SD 3.42,
      range 3-18yr). The Eating and Drinking Ability Classification System (EDACS) and
      the dysphagia scales of Functional Oral Intake Scale (FOIS), Swallow Function
      Scales (SFS), and Food Intake Level Scale (FILS) were used. The Communication
      Function Classification System (CFCS) and Viking Speech Scale (VSS) were employed
      to classify communication function and speech intelligibility, respectively. The
      Pediatric Evaluation of Disability Inventory (PEDI) with the Gross Motor Function
      Classification System (GFMCS) and the Manual Ability Classification System (MACS)
      level were also assessed. Spearman correlation analysis to investigate the
      associations between measures and univariate and multivariate logistic regression
      models to identify significant factors were used. Median GMFCS level of
      participants was III (interquartile range II-IV). Significant dysphagia based on
      EDACS level III-V was noted in 23 children (15.2%). There were strong to very
      strong relationships between the EDACS level with the dysphagia scales. The EDACS
      presented strong associations with MACS, CFCS, and VSS, a moderate association
      with GMFCS level, and a moderate to strong association with each domain of the
      PEDI. In multivariate analysis, poor functioning in EDACS were associated with
      poor functioning in gross motor and communication functions.

PMID- 29223114
TI  - Regional conduction velocity calculation from clinical multichannel electrograms
      in human atria.
AB  - BACKGROUND: During atrial fibrillation, heterogeneities and anisotropies result
      in a chaotic propagation of the depolarization wavefront. The
      electrophysiological parameter called conduction velocity (CV) influences the
      propagation pattern over the atrium. We present a method that determines the
      regional CV for deformed catheter shapes, which result due to the catheter
      movement and changing wall contact. METHODS: The algorithm selects stable
      catheter positions, finds the local activation times (LAT), considers the wall
      contact and calculates all CV estimates within the area covered by the catheter.
      The method is evaluated with simulated data and then applied to four clinical
      data sets. Both sinus rhythm activity as well as depolarization wavefronts
      initiated by stimulation are analyzed. The regional CV is compared with the
      fractionation duration (FD) and peak-to-peak (P2P) voltages. A speed of 0.5 m/s
      was defined to create the simulated LAT. RESULTS: After analyzing the simulated
      LAT with clinical catheter spatial coordinates, the median CV of 0.5 m/s with an
      interquartile range of 0.22 and exact CV direction vectors were obtained. For
      clinical cases, the CV magnitude range of 0.08 m/s to 1.0 m/s was obtained. The
      P2P amplitude of 0.7 mV to 3.7 mV and the mean FD from 40.79ms to 48.66ms was
      obtained. The correlation of 0.86 was observed between CV and P2P amplitude, and
      0.62 between CV and FD. CONCLUSION: In this paper, a method is presented and
      validated which calculates the CV for the deformed catheter and changing wall
      contact. In an exemplary clinical data set correlation between regional CV with
      FD and the P2P voltage was observed.

PMID- 29223115
TI  - Immobilization of hexavalent chromium in contaminated soils using biochar
      supported nanoscale iron sulfide composite.
AB  - Biochar supported carboxymethyl cellulose (CMC)-stabilized nanoscale iron sulfide
      (FeS) composite (CMC-FeS@biochar) was prepared and tested for immobilization of
      hexavalent chromium Cr(VI) in soil. Results of UV-vis and transmission electron
      microscopy (TEM) showed that the backbone of biochar suppressed the aggregation
      of FeS, resulting in smaller particle size and more sorption sites than bare FeS.
      The composite at a dosage of 2.5 mg per gram soil displayed an enhanced Cr(VI)
      immobilization efficiency (a 94.7% reduction in the toxicity characteristic
      leaching procedure (TCLP) based leachability and a 95.6% reduction in the CaCl2
      extraction) compared to plain biochar and bare FeS. Sequential extraction
      procedure (SEP) and X-ray photoelectron spectroscopy (XPS) analysis suggested
      that CMC-FeS@biochar promoted the conversion of more accessible Cr (exchangeable
      and carbonate-bound fractions) into the less accessible forms (iron-manganese
      oxides-bound, organic material-bound, and residual fractions) to reduce the
      toxicity of Cr(VI) and that surface sorption and reduction were dominant
      mechanisms for Cr(VI) immobilization. CMC-FeS@biochar greatly reduced the
      bioavailability of Cr(VI) to wheat and earthworms (Eisenia fetida). Moreover, the
      application of CMC-FeS@biochar enhanced soil organic matter content and microbial
      activity. This work highlighted the potential of CMC-FeS@biochar composite as a
      low-cost, "green", and effective amendment for immobilizing Cr(VI) in
      contaminated soils and improving soil properties.

PMID- 29223116
TI  - Effect of pre-pyrolysis mode on simultaneous introduction of nitrogen/oxygen
      containing functional groups into the structure of bagasse-based mesoporous
      carbon and its influence on Cu(II) adsorption.
AB  - A convenient effective microwave pre-pyrolysis treatment to synthesize biomass
      based mesoporous carbon with higher nitrogen/oxygen-chelating adsorption for
      Cu(II) is reported here, in which phosphoric acid impregnated bagasse was used as
      a microwave absorber and porogen. For comparison, conventional electric-heating
      pyrolyzed carbon was prepared and doped with nitrogen/oxygen groups. Nitrogen
      adsorption, scanning electron microscopy, Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy (XPS) and batch adsorption were
      employed to investigate the effects of the two pre-pyrolysis modes on the sample
      physicochemical and Cu(II) adsorptive properties. The 22-min-microwave-pyrolyzed
      bagasse mesoporous activated carbon (MBAC, 85.32% mesoporosity) contained 10.52%
      O, which is 3.94% more than electric-heating pyrolyzed mesoporous activated
      carbon (89.52% mesoporosity). After electrophilic aromatic substitutions of N/O
      doping, the former possessed more N (5.83%) and more O (21.40%), confirming that
      time-saving energy-efficient microwave pyrolysis favors the formation of
      defective C/O atoms in or at the edges of the graphite layer of MBAC, which are
      highly active and tend to act as preferred reactive positions for the doping of
      N/O-containing groups simultaneously compared with conventional electric-heating
      pyrolysis. These N and O species existed mainly as COOH, OH, NH and NH2
      functional groups, and were confirmed by XPS to be active sites for metal binding
      via electrostatic attraction, hydrogen bonding, a chelate effect and
      complexation, resulting in the great enhancement of Cu(II) adsorption. Langmuir
      isotherm and pseudo-second-order kinetic fitting further proved that Cu(II)
      adsorption by N/O-doped MBAC is ascribed mainly to chemisorption. Therefore,
      rapid microwave pre-pyrolysis provides a promising route to prepare excellent
      performance N/O-doped carbon adsorbents.

PMID- 29223117
TI  - Removal of veterinary antibiotics from wastewater by electrocoagulation.
AB  - The aim of this study was to assess the effectiveness of veterinary antibiotic
      removal from wastewater using an electrocoagulation method. The removal
      efficiency of ampicillin, doxycycline, sulfathiazole and tylosin; the antibiotic
      degradation degree after electrolysis; and the toxicity and qualitative
      composition of antibiotic solutions after electrocoagulation were determined in
      the experiments. HPLC-QTOF was used for quantitative and qualitative
      determination. The eco-toxicity was assessed using the MARA(r) assay. After
      electrocoagulation, the concentration of ampicillin, doxycycline, sulfathiazole
      and tylosin in wastewater decreased 3.6 +/- 3.2%, ~100%, 3.3 +/- 0.4% and 3.1 +/-
      0.3%, respectively. Doxycycline was the only antibiotic effectively removed from
      wastewater during electrocoagulation. Simultaneously, part of this antibiotic
      underwent oxidative degradation. As a result of this process, the eco-toxicity in
      the reaction environment decreased.

PMID- 29223118
TI  - Speciation of chromium compounds from humic acid-zeolite Y to an ionic liquid
      during extraction.
AB  - By synchrotron X-ray absorption spectroscopy, chemical structures of hexavalent
      chromium (Cr(VI))/trivalent chromium (Cr(III)) adsorbed on humic acid (HA)
      zeolite Y and extracted in an ionic liquid (1-butyl-3-methylimidazolium
      tetrafluoroborate ([C4mim][BF4])) have been studied. By combining the competitive
      adsorption results and reduction of Cr(VI)-HA with the carboxyl groups of HA,
      Cr(III)-HA (58%) was shown to be the major compound in HA-zeolite Y using
      synchrotron X-ray absorption near-edge structure (XANES) spectroscopy. In an
      ionic liquid phase, the reduction of Cr(VI)-HA to Cr(III)-HA and the desorption
      of Cr(III) from HA were caused by [C4mim][BF4]. The 9F nuclear magnetic resonance
      (NMR) spectra show that the perturbation of the [C4mim][BF4] anion was affected
      by the extractable chromium species. The formation of a Cr(III) ion affected the
      increase in the bond distance for the 1st shell CrO of the chromium species in
      [C4mim][BF4] using extended X-ray absorption fine structure (EXAFS) spectroscopy.
      The changes in the non-extractable chromium species remaining in HA-zeolite Y
      were also caused by [C4mim][BF4] during extraction. The desorption of the
      absorbed Cr(III) on HA and zeolite Y was observed to form Cr(III) ions. As the
      percentage of Cr(III) ions remaining in HA-zeolite Y increased, a slightly
      greater bond distance for CrO was found at 2.01 A. The enhanced reduction of
      Cr(VI)-HA and desorption of Cr(III) adsorbed on the HA and zeolite Y to form
      Cr(III) ions were affected by [C4mim][BF4]. Increased mobility of Cr(III) in the
      simulated soil can promote the migration of Cr(III) ions into the H2O during soil
      washing for remediation.

PMID- 29223119
TI  - Bio fabrication of silver nanoparticles as an effective wound healing agent in
      the wound care after anorectal surgery.
AB  - Nowadays biological mediated syntheses of metal nanoparticles were utilized for
      various life caring applications. Our research group utilized Delonix elata leaf
      aqueous extract for the synthesis of silver nanoparticles. Further the
      synthesized silver nanoparticles were subjected for various characterization
      techniques which resulted in spherically agglomerated with biological components
      entrapped in it and also with average particle size of 36nm were studied and
      reported. Later the synthesized silver nanoparticles were subjected for wound
      healing property by size of measured lessions and body weight which results in
      better wound healing property were studied and discussed.

PMID- 29223120
TI  - De-icing salt contamination reduces urban tree performance in structural soil
      cells.
AB  - Salts used for de-icing roads and sidewalks in northern climates can have a
      significant impact on water quality and vegetation. Sub-surface engineering
      systems, such as structural soil cells, can regulate water runoff and pollutants,
      and provide the necessary soil volume and irrigation to grow trees. However, the
      ability of such systems to manage de-icing salt contamination, and the impact of
      this contamination on the trees growing in them, have not been evaluated. We
      report on an field investigation of de-icing salt contamination in structural
      cells in two street-revitalization projects in Toronto, Canada, and the impact of
      this contamination on tree performance. We analyzed soil chemistry and collected
      tree attributes; these data were examined together to understand the effect of
      salinity on tree mortality rates and foliar condition. Data collected from
      continuous soil salinity loggers from April to June for one of the two sites were
      used to determine whether there was a long-term accumulation of salts in the
      soils. Results for both sites indicate that both sites displayed high salinity
      and alkalinity, with levels elevated beyond those suggested before those reported
      to cause negative tree effects. For one site, trees that were alive and trees
      that had a better foliar condition had significantly lower levels of soil
      salinity and alkalinity than other trees. High salinity and alkalinity in the
      soil were also associated with lower nutrient levels for both sites. Although
      tests for salinity accumulation in the soils of one site were negative, a longer
      monitoring of the soil conditions within the soil cells is warranted. Despite
      structural cells being increasingly utilized for their dual role in storm-water
      management and tree establishment, there may be a considerable trade-off between
      storm-water management and urban-forest function in northern climates where de
      icing salt application continues to be commonplace.

PMID- 29223121
TI  - From information to participation and self-organization: Visions for European
      river basin management.
AB  - The European Union Water Framework Directive (EU WFD, 2000) calls for active
      inclusion of the public in the governance of waterbodies to enhance the
      effectiveness and legitimacy of water management schemes across the EU. As
      complex socio-ecological systems, river basins in western Europe could benefit
      from further support for inclusive management schemes. This paper makes use of
      case studies from Germany, England and Spain to explore the potential
      opportunities and challenges of different participatory management approaches.
      Grounded in theoretical considerations around participation within ecological
      management schemes, including Arnstein's Ladder of Participation and commons
      theories, this work provides an evaluation of each case study based on key
      indicators, such as inclusivity, representativeness, self-organization, decision
      making power, spatial fit and temporal continuity. As investors and the public
      develop a heightened awareness for long-term sustainability of industrial
      projects, this analysis supports the suggestion that increased participatory
      river basin management is both desirable and economically feasible, and should
      thus be considered a viable option for future projects aiming to move beyond
      current requirements of the European Union Water Framework Directive.

PMID- 29223122
TI  - A comprehensive review of spatial allocation of LID-BMP-GI practices: Strategies
      and optimization tools.
AB  - Low-impact development (LID), best management practice (BMP), and green
      infrastructure (GI) are semi-engineered stormwater management practices that have
      been widely studied and implemented worldwide. Implemented in the complex
      environment of urban areas, LID-BMP-GI practices often intertwine with a very
      large number of hydro-environmental and socio-economic considerations and
      constraints. Therefore, they need to be carefully selected, designed, and
      allocated within an urban area. Both planning and optimization can lead to more
      systematic and strategic approaches to address this multi-scale, multi-parameter
      problem of practice allocation. In this review, we first identify the main
      components of the strategic planning cycle, their scope and inter-relationships,
      and their corresponding mathematical representations. We then present a
      comprehensive review of the existing literature on spatial allocation
      optimization tools (SAOTs) for LID-BMP-GI practices and summarize the generic
      structure and the systematic typology of the existing SAOTs. We conclude with a
      discussion of several current research gaps in the spatial allocation of LID-BMP
      GI practices. In this review, we aim to summarize the strategies and optimization
      tools for the spatial allocation of LID-BMP-GI practices that are beneficial to
      practitioners. The other aim is to provide recommendations for future research on
      the development of more advanced and comprehensive SAOTs.

PMID- 29223123
TI  - Differentiation of human blood from animal blood using Raman spectroscopy: A
      survey of forensically relevant species.
AB  - The identification of blood samples is a crucial facet of forensic
      investigations, particularly for violent crimes. One step in forensic serology
      (i.e., the analysis of bodily fluids) that is often skipped or overlooked is the
      determination that a bloodstain is of human or nonhuman origin. Typically,
      subsequent to identifying a stain as blood using a presumptive blood test, which
      have the propensity of providing false positive results, the stain is submitted
      for extraction of a DNA profile to compare with those in a database. It is
      extremely uncommon that evidentiary bloodstains are confirmed as being of human
      origin throughout the serological analysis. Therefore, time, money, and other
      resources can be wasted on obtaining a DNA profile from a bloodstain that may not
      be of human origin; if the intent was to obtain a human DNA profile and not that
      of an animal. This work demonstrates an important advancement of a previous study
      for nondestructive differentiation of human and animal blood using Raman
      spectroscopy coupled with partial least squares discriminant analysis (PLSDA).
      Raman spectra of blood from six species of animals, not previously accounted for,
      including chimpanzee, deer, elk, ferret, fish, and macaque were used to test a
      PLSDA classification method. These animal species are forensically relevant since
      they are (i) involved in wildlife crimes, (ii) consumed by humans, or (iii) known
      to produce a false positive result when their blood is tested with certain
      presumptive human blood tests. An external validation sensitivity of 1.00 and
      specificity of 0.93 for human class predictions was obtained from the PLSDA model
      constructed for this study. Using receiver operating characteristic (ROC)
      analysis of external human class predictions, the PLSDA model demonstrated 99%
      accuracy in being able to correctly classify any random blood sample as human or
      nonhuman. This is a significant advancement over the previous work and a very
      important finding as it demonstrates the superb selectivity of the developed
      method with high accuracy in being able to correctly predict the nonhuman origin
      of bloodstains from unknown animal species.

PMID- 29223124
TI  - Activation of mitochondrial KATP channels mediates neuroprotection induced by
      chronic morphine preconditioning in hippocampal CA-1 neurons following cerebral
      ischemia.
AB  - PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and
      mediators, can increase the tolerance of different tissues against
      ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine
      preconditioning has protective effects in different organs, especially in the
      heart. Nevertheless, its mechanisms are not well elucidated in the brain. The
      present study aimed to clarify whether the activation of mitochondrial KATP
      (mKATP) channels in chronic morphine (CM) preconditioning could decrease
      hippocampus damage following I/R injury. MATERIALS AND METHODS: CM
      preconditioning was performed by the administration of additive doses of morphine
      for 5days before I/R injury induction. I/R injury was induced by the occlusion of
      bilateral common carotid arteries. The possible role of mKATP channels was
      evaluated by the injection of 5-hydroxydecanoate (5-HD) before I/R injury.
      Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was
      performed to detect apoptosis in hippocampal neurons. The expressions of B-cell
      lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (BAX) and levels of
      malondialdehyde (MDA) and catalase (CAT) enzymes were assessed. RESULTS: CM
      attenuated apoptosis in the hippocampal CA1 neurons (P<0.001 vs I/R), and mKATP
      channel blocking with 5-HD significantly increased apoptosis (P<0.001 vs CM+I/R).
      CM increased CAT activity (P<0.05 vs I/R) and Bcl-2 protein expression (P<0.01 vs
      I/R), while it decreased MDA level (P<0.05 vs I/R) and BAX protein expression
      (P<0.05 vs I/R). Pretreatment with 5-HD abolished all the above-mentioned effects
      of CM. CONCLUSIONS: These findings describe novel evidence whereby CM
      preconditioning in hippocampal CA1 neurons can improve oxidative stress and
      apoptosis through the activation of mKATP channels and eventually protect the
      hippocampal tissue against I/R injury.

PMID- 29223125
TI  - TGF-beta and inflammatory blood markers in prediction of intraperitoneal
      adhesions.
AB  - PURPOSE: Intraperitoneal adhesions (IA) develop as a consequence of the healing
      process in peritoneum injured during surgeries. IA might be formed after all
      types of surgical interventions regardless the surgical approach with a higher
      incidence in obese individuals. Here we determine the diagnostic power of TGF
      beta and blood inflammatory parameters in the prediction of IA in obese patients
      undergoing second surgical intervention. MATERIALS AND METHODS: Eighty patients
      were divided into groups according to body mass index (BMI) values and presence
      of intraperitoneal adhesions (IA). Evaluation of peritoneal adhesion index (PAI),
      serum TGF-beta and blood inflammatory parameters was performed. RESULTS: Level of
      TGF-beta, C-reactive protein (CRP), leukocytes, neutrophil to lymphocyte ratio
      and platelet to lymphocyte ratio were significantly higher in obese patients
      while TGF-beta, CRP, and leukocytes were higher in patients with IA. There was a
      significant correlation between PAI values and TGF-beta concentration (p<0.001;
      r=0.869) in IA group. CONCLUSIONS: The preoperative TGF-beta concentration, BMI,
      CRP and NLR could be strong predictors of intraperitoneal adhesions in patients
      with the history of surgeries.

PMID- 29223126
TI  - HPeV-3 predominated among Parechovirus A positive infants during an outbreak in
      2013-2014 in Queensland, Australia.
AB  - BACKGROUND: Parechoviruses (HPeV) are endemic seasonal pathogens detected from
      the respiratory tract, gut, blood and central nervous system (CNS) of children
      and adults, sometimes in conjunction with a range of acute illnesses. HPeV CNS
      infection may lead to neurodevelopmental sequelae, especially following infection
      by HPeV-3, hence screening and genotyping are important to inform epidemiology,
      aetiology and prognosis. OBJECTIVES: To identify and characterise HPeVs
      circulating during an outbreak between November 2013 and April 2014 in
      Queensland, Australia. STUDY DESIGN: To perform PCR-based screening and
      comparative nucleotide sequence analysis on samples from children with clinically
      suspected infections submitted to a research laboratory for HPeV investigations.
      RESULTS: HPeVs were detected among 25/62 samples, identified as HPeV-3 from 23
      that could be genotyped. These variants closely matched those which have occurred
      worldwide and in other States of Australia. CONCLUSIONS: The inclusion of PCR
      based HPeV testing is not systematically applied but should be considered
      essential for children under 3 months of age with CNS symptoms as should long
      term follow-up of severe sepsis-like cases.

PMID- 29223127
TI  - Be my baby: patterning toward plant germ cells.
AB  - In flowering plants, germ cells are formed via tightly coordinated patterning
      processes that facilitate specification of spore mother cells and meiosis during
      sporogenesis, as well as functional differentiation of germ cells in
      gametogenesis. Studies using the conventional Arabidopsis system and the newly
      emerged bryophyte system have revealed novel interactions between regulatory
      factors that restrict the number of spore mother cells, and evolutionarily
      conserved factors that promote germ cell differentiation. This short review
      summarizes recent advances in our understanding of the cellular events that lead
      to the formation of germ cells in plants, and highlights questions that remain to
      be addressed in the field.

PMID- 29223128
TI  - Child protective services utilization of child abuse pediatricians: A mixed
      methods study.
AB  - Several children's hospitals and medical schools across Texas have child abuse
      pediatricians (CAPs) who work closely with child protection workers to help
      ensure accurate assessments of the likelihood of maltreatment in cases of
      suspected abuse and neglect. Since the state does not mandate which cases should
      be referred to a CAP center, we were interested in studying factors that may
      influence workers' decisions to consult a CAP. We used a mixed methods study
      design consisting of a focus group followed by a survey. The focus group
      identified multiple factors that impact workers' decision-making, including
      several that involve medical providers. Responses from 436 completed surveys were
      compared to employees' number of years of employment and to the state region in
      which they worked. Focus group findings and survey responses revealed frustration
      among many workers when dealing with medical providers, and moderate levels of
      confidence in workers' abilities to make accurate determinations in cases
      involving medical information. Workers were more likely to refer cases involving
      serious physical injury than other types of cases. Among workers who reported
      prior interactions with a CAP, experiences and attitudes regarding CAPs were
      typically positive. The survey also revealed significant variability in referral
      practices by state region. Our results suggest that standard guidelines regarding
      CAP referrals may help workers who deal with cases involving medical information.
      Future research and quality improvement efforts to improve transfers of
      information and to better understand the qualities that CPS workers appreciate in
      CAP teams should improve CAP-CPS coordination.

PMID- 29223130
TI  - The expression of the embryonic gene Cripto-1 is regulated by OCT4 in human
      embryonal carcinoma NCCIT cells.
AB  - Cripto-1 and OCT4, expressed in stem cells and cancers, play important roles in
      tumorigenesis. Here, we demonstrate that Cripto-1 expression is regulated by OCT4
      in human embryonic carcinoma NCCIT cells. The endogenous expression of Cripto-1
      and OCT4 is significantly reduced during differentiation. Cripto-1 expression is
      increased by OCT4 overexpression, but decreased by shRNA-mediated OCT4 knockdown.
      OCT4 overexpression significantly activates Cripto-1 transcriptional activity. A
      5'-upstream minimal promoter sequence in the gene-encoding Cripto-1 is
      significantly activated by OCT4 overexpression. Mutation of the putative OCT4
      binding site abolishes OCT4-mediated activation of the Cripto-1 promoter. The
      OCT4 transactivation domains mediate transcriptional activity of the Cripto-1
      minimal promoter through direct interaction. Taken together, OCT4 plays an
      important role as a transcriptional activator of Cripto-1 expression in NCCIT
      cells.

PMID- 29223129
TI  - The M458L missense mutation disrupts the catalytic properties of Parkin.
AB  - Parkin encodes an E3 ubiquitin ligase, and mutations affecting its catalytic
      potential are implicated in autosomal recessive Parkinson's disease (PD). The
      M458L mutation of parkin and its enzymatic effects require characterization.
      Therefore, we examined the enzymatic activity of Parkin with M458L mutation. We
      show that the M458L mutant retains its autoubiquitination potential in vitro but
      not in cells. Fas-associated factor 1 and p38 (substrates of Parkin) are able to
      bind to the M458L mutant in cells; however, these Parkin substrates are not
      ubiquitinated and degraded in M458L mutant-transfected cells. Moreover, M458L
      mutant fails to protect the mitochondria against hydrogen peroxide, leading to
      cell death. Considering the role of mitochondrial dysfunction in PD pathogenesis,
      our results imply a causative role for the M458L mutation in neurodegeneration.

PMID- 29223131
TI  - Photodynamic therapy in the treatment of symptomatic oral lichen planus: A
      systematic review.
AB  - BACKGROUND: The aim of this systematic review was to assess the efficacy of
      photodynamic therapy (PDT) in the treatment of symptomatic oral lichen planus
      (OLP). METHODS: This systematic review aimed to address the following focused
      question: "Is PDT effective in the treatment of symptomatic OLP?" Indexed
      databases such as MEDLINE, EMBASE, and CENTRAL were searched up to and including
      August 2017. RESULTS: Six clinical studies were included. The risk of bias was
      considered high in 5 studies and moderate in one study. Parameters of PDT such as
      wavelengths, energy fluence, power density and exposure time ranged between 320
      660 nm, 120 J/cm2 , 130 mW/cm2 , and 70-150 seconds, respectively. The follow-up
      period ranged from 4 to 48 weeks. All included studies reporting clinical scores
      showed that PDT was effective in the treatment of OLP in adult patients at follow
      up. However, PDT did not show significant improvement when compared with steroid
      therapy. CONCLUSION: Photodynamic therapy appears to have some effect in the
      symptomatic treatment of OLP in adult patients. However, further randomized
      controlled trials with long follow-up period, standardized PDT parameters, and
      comparing the efficacy of PDT with steroid therapy are warranted to obtain strong
      conclusions in this regard.

PMID- 29223132
TI  - Homelessness and Emergency Medicine: A Review of the Literature.
AB  - OBJECTIVES: We aimed to synthesize the available evidence on the demographics,
      prevalence, clinical characteristics, and evidence-based management of homeless
      persons in the emergency department (ED). Where appropriate, we highlight
      knowledge gaps and suggest directions for future research. METHODS: We conducted
      a systematic literature search following databases: PubMed, Ovid, and Google
      Scholar for articles published between January 1, 1990, and December 31, 2016. We
      supplemented this search by cross-referencing bibliographies of the retrieved
      publications. Peer-reviewed studies written in English and conducted in the
      United States that examined homelessness within the ED setting were included. We
      used a qualitative approach to synthesize the existing literature. RESULTS:
      Twenty-eight studies were identified that met the inclusion criteria. Based on
      our study objectives and the available literature, we grouped articles examining
      homeless populations in the ED into four broad categories: 1) prevalence and
      sociodemographic characteristics of homeless ED visits, 2) ED utilization by
      homeless adults, 3) clinical characteristics of homeless ED visits, and 4)
      medical education and evidence-based management of homeless ED patients.
      CONCLUSION: Homelessness may be underrecognized in the ED setting. Homeless ED
      patients have distinct care needs and patterns of ED utilization that are unmet
      by the current disease-oriented and episodic models of emergency medicine. More
      research is needed to determine the prevalence and characteristics of
      homelessness in the ED and to develop evidence-based treatment strategies in
      caring for this vulnerable population.

PMID- 29223133
TI  - How stress contributes to autoimmunity-lessons from Sjogren's syndrome.
AB  - A large body of clinical evidence on the association between stressful life
      events and autoimmune diseases suggests that stress may play an important role in
      the pathogenesis of these disorders. In this article, we discuss the effects of
      stress, not on the immune system but on specific cell populations against which
      the autoimmune reactivity is directed. Using Sjogren's syndrome as a model
      autoimmune disease, we review the role of stress in the initiation and
      perpetuation of autoimmune reactivity. We present data that reveal the effects of
      stress on salivary gland epithelial cells, suggesting that stress can become
      immunogenic through its various effects on salivary gland epithelium.

PMID- 29223134
TI  - Rapid soil formation after glacial retreat shaped by spatial patterns of organic
      matter accrual in microaggregates.
AB  - Global change contributes to the retreat of glaciers at unprecedented rates. The
      deglaciation facilitates biogeochemical processes on glacial deposits with
      initiating soil formation as an important driver of evolving ecosystems. The
      underlying mechanisms of soil formation and the association of soil organic
      matter (SOM) with mineral particles remain unclear, although further insights are
      critical to understand carbon sequestration in soils. We investigated the
      microspatial arrangement of SOM coatings at intact soil microaggregate structures
      during various stages of ecosystem development from 15 to >700 years after
      deglaciation in the proglacial environment of the Damma glacier (Switzerland).
      The functionally important clay-sized fraction (<2 MUm) was separated into two
      density fractions with different amounts of organo-mineral associations: light
      (1.6-2.2 g/cm3 ) and heavy (>2.2 g/cm3 ). To quantify how SOM extends across the
      surface of mineral particles (coverage) and whether SOM coatings are distributed
      in fragmented or connected patterns (connectivity), we developed an image
      analysis protocol based on nanoscale secondary ion mass spectrometry (NanoSIMS).
      We classified SOM and mineral areas depending on the 16 O- , 12 C- , and 12 C14 N
      distributions. With increasing time after glacial retreat, the microspatial
      coverage and connectivity of SOM increased rapidly. The rapid soil formation led
      to a succession of patchy distributed to more connected SOM coatings on soil
      microaggregates. The maximum coverage of 55% at >700 years suggests direct
      evidence for SOM sequestration being decoupled from the mineral surface, as it
      was not completely masked by SOM and retained its functionality as an ion
      exchange site. The chemical composition of SOM coatings showed a rapid change
      toward a higher CN:C ratio already at 75 years after glacial retreat, which was
      associated with microbial succession patterns reflecting high N assimilation. Our
      results demonstrate that rapid SOM sequestration drives the microspatial
      succession of SOM coatings in soils, a process that can stabilize SOM for the
      long term.

PMID- 29223135
TI  - Simultaneous anti-diabetic and anti-vascular calcification activity of Nocardia
      sp. UTMC 751.
AB  - : Alpha-amylase can act as a significant player in causing hyperglycaemia,
      leading to protein glycation, which is the main complication in this condition,
      besides causing vascular calcification (VC), an important vascular failure caused
      due to this. In order to find a natural source of the biocompounds with
      inhibitory effects on alpha-amylase, 15 fermentation broth extracts of
      actinobacteria (FBEA) (200 MUg ml-1 ) have been screened. Finally, the effects of
      the most efficient FBE have been investigated on osteopontin (OPN, a VC marker)
      mRNA level in the vascular smooth muscle cells under the calcification
      conditions, and the chemical constituents of the most efficient FBE were analysed
      using gas chromatography and mass spectrometry (GC-MS) analysis. The tested FBEA
      showed anti-amylase (7.2-21%) and anti-denaturation (7.5-37%) activities. Among
      the tested FBEA, Nocardia sp. UTMC 751 FBE showed the highest anti-amylase
      activity (21%). This treatment group also displayed the minimum fructosamine and
      the maximum thiol groups content. In addition, this FBE reduced the mRNA level of
      the OPN (fourfold). The GC-MS analysis demonstrated the existence of three
      volatile and known antioxidants including pyrrolo[1,2-a]pyrazine-1,4-dione,
      hexahydro-3-(2-methylpropyl)-, pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3
      (phenylmethyl)- and methyl ester of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)
      propionic acid in the FBE of Nocardia sp. UTMC 751. The results indicated that
      Nocardia sp. UTMC 751 is a considerable source of bioactive compounds that are
      effective against the direct and indirect pathological targets involved in
      diabetes. This study highlights the significant potential of rare Actinomycetes
      in producing pharmaceutically important biocompounds. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Actinobacteria are one of the best natural libraries for discovering
      drugs. Various commercial drugs have been developed against infectious and
      metabolic disorders from actinobacteria; however, there is no report on their
      simultaneous inhibitory effect against diabetes, a life-threatening disease, and
      its related pathological processes, like inflammation and vascular calcification
      (VC). In this research, after several screening, Nocardia sp. UTMC 751 was
      introduced as the first microbial source exhibiting a simultaneous inhibitory
      activity on the targets, including hyperglycaemia and protein glycation, and
      other involved pathological processes like inflammation and VC.

PMID- 29223136
TI  - Allele exchange at the EPSPS locus confers glyphosate tolerance in cassava.
AB  - Effective weed control can protect yields of cassava (Manihot esculenta) storage
      roots. Farmers could benefit from using herbicide with a tolerant cultivar. We
      applied traditional transgenesis and gene editing to generate robust glyphosate
      tolerance in cassava. By comparing promoters regulating expression of transformed
      5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) genes with various paired
      amino acid substitutions, we found that strong constitutive expression is
      required to achieve glyphosate tolerance during in vitro selection and in whole
      cassava plants. Using strategies that exploit homologous recombination (HR) and
      nonhomologous end-joining (NHEJ) DNA repair pathways, we precisely introduced the
      best-performing allele into the cassava genome, simultaneously creating a
      promoter swap and dual amino acid substitutions at the endogenous EPSPS locus.
      Primary EPSPS-edited plants were phenotypically normal, tolerant to high doses of
      glyphosate, with some free of detectable T-DNA integrations. Our methods
      demonstrate an editing strategy for creating glyphosate tolerance in crop plants
      and demonstrate the potential of gene editing for further improvement of cassava.

PMID- 29223137
TI  - Sysmex UF-1000i flow cytometer to screen urinary tract infections: the URISCAM
      multicentre study.
AB  - : The new Sysmex UF-1000i analyzer - which incorporates bacteria morphology
      distinction - allows to automatically screen samples to be cultured at
      microbiology laboratories. We have evaluated the feasibility and accuracy of
      Sysmex UF-1000i to screen urinary tract infections (UTIs). A total amount of 2468
      urine samples from six Spanish hospitals were analysed. Demographic and clinical
      data such as age, gender, source and sample type, preserving conditions,
      cytometer parameters (bacteria, leucocytes and bacteria morphology) as well as
      urine culture results (gold standard) were recorded. After applying data mining
      techniques, the variables of age, bacteria count and rod morphology were defined
      as predictive variables of UTIs. By using the UF-1000i in combination with a
      predictive algorithm of three decision rules, we could identify 94.9 and 47.4%
      positive and negative urine samples, respectively, with a negative predictive
      value of 97 and only 1.17% diagnostic error. This error was reduced down to 0.4%
      when contaminated samples were excluded. Our results show that flow cytometry
      parameters together with age, by means of a predictive algorithm model, can be
      used to screen UTIs. Its implementation would avoid culturing 38% of urine
      samples, and therefore, would reduce time to diagnosis with a discrete false
      negative ratio. SIGNIFICANCE AND IMPACT OF THE STUDY: Fluorescent flow cytometry
      performance has recently spread for urine screening. However, controversy about
      cytometer results can be drawn from medical literature. This study shows the
      diagnosis accuracy of Sysmex UF-1000i analyzer by means of a group of decision
      rules encompassing both demographic variables (age) and cytometer parameters
      (bacteria, leucocytes and bacteria morphology). After applying the predictive
      algorithm, the UF-1000i could optimally identify 95% urinary tract infections
      with high negative predictive value and low diagnostic error. Implementation of
      UF-1000i would avoid culturing almost 38% of urine samples, thus reducing time to
      diagnosis, unnecessary antibiotic treatments and consequently improving cost
      effectiveness.

PMID- 29223138
TI  - Plant-expressed Fc-fusion protein tetravalent dengue vaccine with inherent
      adjuvant properties.
AB  - Dengue is a major global disease requiring improved treatment and prevention
      strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not
      protect children under the age of nine, and additional vaccine strategies are
      thus needed to halt this expanding global epidemic. Here, we employed a molecular
      engineering approach and plant expression to produce a humanized and highly
      immunogenic poly-immunoglobulin G scaffold (PIGS) fused to the consensus dengue
      envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor
      targeted vaccine candidate was demonstrated in transgenic mice expressing human
      FcgammaRI/CD64, by induction of neutralizing antibodies and evidence of cell
      mediated immunity. Furthermore, these molecules were able to prime immune cells
      from human adenoid/tonsillar tissue ex vivo as evidenced by antigen-specific CD4+
      and CD8+ T-cell proliferation, IFN-gamma and antibody production. The purified
      polymeric fraction of dengue PIGS (D-PIGS) induced stronger immune activation
      than the monomeric form, suggesting a more efficient interaction with the low
      affinity Fcgamma receptors on antigen-presenting cells. These results show that
      the plant-expressed D-PIGS have the potential for translation towards a safe and
      easily scalable single antigen-based tetravalent dengue vaccine.

PMID- 29223139
TI  - Novel treatments for inflammatory bowel disease.
AB  - Increased understanding of the immunopathology of inflammatory bowel disease
      (IBD) has led to the development of targeted therapies and has unlocked a new era
      in IBD treatment. The development of treatment options aimed at a variety of
      pathological mechanisms offers new hope for customized therapies. Beyond anti
      tumor necrosis factor agents, selective lymphocyte trafficking inhibitors have
      been proposed as potent drugs for IBD. Among these, vedolizumab has recently been
      approved for both Crohn's disease and ulcerative colitis. Numerous other agents
      for IBD treatment are currently under investigation, including Janus kinase
      inhibitors, anti-mucosal vascular addressin cell adhesion molecule-1 agents, an
      anti-SMAD7 antisense oligonucleotide, an anti-interleukin-12/23 monoclonal
      antibody, and a sphingosine-1-phosphate receptor-1 selective agonist. These
      agents will likely expand the treatment options available for the management of
      IBD patients in the future. In this review, we discuss the efficacy and safety of
      novel agents currently under investigation in IBD clinical trials.

PMID- 29223140
TI  - Collagen-Induced Arthritis Analysis in Rhbdf2 Knockout Mouse.
AB  - Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential
      catalytic residues of rhomboid intramembrane serine proteases. The protein is
      necessary for maturation of tumor necrosis factor-alpha (TNF-alpha) converting
      enzyme, which is the molecule responsible for the release of TNF-alpha. In this
      study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects
      of the failure of TNF-alpha release induced by Rhbdf2 gene KO, collagen-induced
      arthritis (CIA), which is the representative TNF-alpha related disease, was
      induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity
      of the CIA was measured by traditional clinical scores and histopathological
      analysis of hind limb joints. A rota-rod test and grip strength test were
      employed to evaluate the severity of CIA based on losses of physical functions.
      The results indicated that Rhbdf2 mutant mice showed clear alleviation of the
      clinical severity of CIA as demonstrated by the significantly lower severity
      indexes. Moreover, a grip strength test was shown to be useful for the evaluation
      of physical functional losses by CIA. Overall, the results showed that the Rhbdf2
      gene has a significant effect on the induction of CIA, which is related to TNF
      alpha.

PMID- 29223141
TI  - Molecular and Functional Characterization of Choline Transporter-Like Proteins in
      Esophageal Cancer Cells and Potential Therapeutic Targets.
AB  - In this study, we examined the molecular and functional characterization of
      choline uptake in the human esophageal cancer cells. In addition, we examined the
      influence of various drugs on the transport of [3H]choline, and explored the
      possible correlation between the inhibition of choline uptake and apoptotic cell
      death. We found that both choline transporter-like protein 1 (CTL1) and CTL2
      mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE
      series). CTL1 and CTL2 were located in the plasma membrane and mitochondria,
      respectively. Choline uptake was saturable and mediated by a single transport
      system, which is both Na+-independent and pH-dependent. Choline uptake and cell
      viability were inhibited by various cationic drugs. Furthermore, a correlation
      analysis of the potencies of 47 drugs for the inhibition of choline uptake and
      cell viability showed a strong correlation. Choline uptake inhibitors and choline
      deficiency each inhibited cell viability and increased caspase-3/7 activity. We
      conclude that extracellular choline is mainly transported via a CTL1. The
      functional inhibition of CTL1 by cationic drugs could promote apoptotic cell
      death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which
      is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA
      methylation. Identification of this CTL1- and CTL2-mediated choline transport
      system provides a potential new target for esophageal cancer therapy.

PMID- 29223142
TI  - Designing Tyrosinase siRNAs by Multiple Prediction Algorithms and Evaluation of
      Their Anti-Melanogenic Effects.
AB  - Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has
      a protective role against UVB radiation-induced damage, it is also associated
      with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme
      in melanin synthesis, which regulates the rate-limiting step during conversion of
      tyrosine into DOPA and dopaquinone. To develop effective RNA interference
      therapeutics, we designed a melanin siRNA pool by applying multiple prediction
      programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target
      accessibility evaluation using the RNAxs program. Then we selected 34 siRNA
      sequences with DeltaG >=-34.6 kcal/mol, i-Score value >=65, and siRNA scales
      score <=30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3'
      overhang at the 3' end of the antisense strand. We tested if these siRNAs
      effectively reduced tyrosinase gene expression using qRT-PCR and found that 17
      siRNA sequences were more effective than commercially available siRNA. Three
      siRNAs further tested showed an effective visual color change in MNT-1 human
      cells without cytotoxic effects, indicating these sequences are anti-melanogenic.
      Our study revealed that human tyrosinase siRNAs could be efficiently designed
      using multiple prediction algorithms.

PMID- 29223145
TI  - Antibody biosensors for the measurement and characterization of soluble CD147
      molecules.
AB  - BACKGROUND: Soluble CD147 (sCD147) is the shed form of membrane-bound CD147,
      which is involved in the regulation of cellular functions. The presence of sCD147
      in body fluids is associated with several diseases. OBJECTIVE: In this study, we
      aimed to establish antibody (Ab) biosensors for the simultaneous differential
      detection of the general and truncated forms of sCD147. METHOD: By combining
      biolayer interferometry technology (BLItz) and different anti-CD147 monoclonal
      antibodies (mAbs) specific to different extracellular domains of the CD147
      molecule, Ab-based biosensors were established to rapidly measure and
      characterize sCD147 isoforms. RESULTS: Two types of Ab-biosensors, desginated the
      single Ab-biosensor and double Ab-biosensor, were established for the measurment
      and characterization of sCD147 isoforms. For the single Ab-biosensor system,
      monoclonal antibodies specific for CD147 domain 1 (D1) or domain 2 (D2) were
      immobilized on the sensor tips and used for the quantification of sCD147 using a
      BLItz optical interferometric biosensor. For the double Ab-biosensor system,
      following the single Ab-biosensor step, secondary anti-CD147 mAbs specific for
      each domain of the CD147 molecule were added and monitored by a BLItz biosensor.
      By combining the results obtained from the single Ab- and double Ab-biosensors,
      sCD147 isoforms including the general form (D1 linked to D2) and the truncated
      forms (sCD147 containing D1 or D2) could be determined. CONCLUSIONS: This method
      may be a beneficial tool for the determination of sCD147 isoforms for disease
      diagnosis and prognosis as well as for the definition of the cellular mechanisms
      of the immune system.

PMID- 29223144
TI  - Role of Carbon Monoxide in Neurovascular Repair Processing.
AB  - Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase
      (HO). Endogenous CO production occurring at low concentrations is thought to have
      several useful biological roles. In mammals, especially humans, a proper
      neurovascular unit comprising endothelial cells, pericytes, astrocytes,
      microglia, and neurons is essential for the homeostasis and survival of the
      central nervous system (CNS). In addition, the regeneration of neurovascular
      systems from neural stem cells and endothelial precursor cells after CNS diseases
      is responsible for functional repair. This review focused on the possible role of
      CO/HO in the neurovascular unit in terms of neurogenesis, angiogenesis, and
      synaptic plasticity, ultimately leading to behavioral changes in CNS diseases.
      CO/HO may also enhance cellular networks among endothelial cells, pericytes,
      astrocytes, and neural stem cells. This review highlights the therapeutic effects
      of CO/HO on CNS diseases involved in neurogenesis, synaptic plasticity, and
      angiogenesis. Moreover, the cellular mechanisms and interactions by which CO/HO
      are exploited for disease prevention and their therapeutic applications in
      traumatic brain injury, Alzheimer's disease, and stroke are also discussed.

PMID- 29223143
TI  - Neurobiological Functions of the Period Circadian Clock 2 Gene, Per2.
AB  - Most organisms have adapted to a circadian rhythm that follows a roughly 24-hour
      cycle, which is modulated by both internal (clock-related genes) and external
      (environment) factors. In such organisms, the central nervous system (CNS) is
      influenced by the circadian rhythm of individual cells. Furthermore, the period
      circadian clock 2 (Per2) gene is an important component of the circadian clock,
      which modulates the circadian rhythm. Per2 is mainly expressed in the
      suprachiasmatic nucleus (SCN) of the hypothalamus as well as other brain areas,
      including the midbrain and forebrain. This indicates that Per2 may affect various
      neurobiological activities such as sleeping, depression, and addiction. In this
      review, we focus on the neurobiological functions of Per2, which could help to
      better understand its roles in the CNS.

PMID- 29223146
TI  - Investigation of mast cell toll-like receptor 3 in Chronic Fatigue
      Syndrome/Myalgic Encephalomyelitis and Systemic Mastocytosis participants using
      the novel application of autoMACS magnetic separation and flow cytometry.
AB  - BACKGROUND: Viral infections and hypersensitivities are commonly reported by
      Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. Mast Cells
      (MC) uniquely mediate type 1 hypersensitivities and resolve viral infections via
      toll-like receptor 3 (TLR3). OBJECTIVE: To characterise and compare mast cell
      progenitors (MCPs) in CFS/ME participants with a known MC disorder, Systemic
      mastocytosis (SM), and secondly, to investigate the role of MC TLR3 in CFS/ME
      participants following Polyinosinic:polycytidylic acid (Poly I:C) stimulation.
      METHODS: A total of 11 International Consensus Criteria defined CFS/ME
      participants (40.42 +/- 10.31), 9 World Health Organisation defined systemic
      mastocytosis (SM) participants (47.00 +/- 10.37) and 12 healthy controls (HC)
      (36.36 +/- 9.88) were included. Following autoMACS magnetic separation,
      CD117+/Lin-MCPs were stimulated with Poly I:C for 24hr. MCP purity (CD117 and
      Lin2), maturity (CD34 and FcepsilonRI), interaction receptors and ligands (CD154
      and HLA-DR), and SM-specific (CD2 and CD25) markers were measured using flow
      cytometry. RESULTS: There was a significant decrease in HLA-DR+/CD154- expression
      between CFS/ME and SM groups pre and post Poly I:C stimulation. There were no
      significant differences in maturity MCPs, CD154, and CD2/CD25 expression between
      groups pre and post Poly I:C stimulation. CONCLUSION: This pilot investigation
      provides a novel methodology to characterise MCPs in a rapid, inexpensive and
      less invasive fashion. We report a significant decrease in HLA-DR+/CD154-
      expression between CFS/ME and SM participants, and an observed increase in HLA-DR
      /CD154+ expression post Poly I:C stimulation in CFS/ME participants. Peripheral
      MCPs may be present in CFS/ME pathophysiology, however further investigation is
      required to determine their immunological role.

PMID- 29223147
TI  - The unmet provision of allergy services in Hong Kong impairs capability for
      allergy prevention-implications for the Asia Pacific region.
AB  - There is a high and rising prevalence of many allergic diseases in the Asia
      Pacific, including Hong Kong, which is unmatched by a commensurate provision of
      clinical allergy services. In the last 3 years, the allergy profile in Hong Kong
      has increased due to greater public engagement and more frequent educational
      activities, scientific outputs and publication of local guidelines on allergy
      prevention, diagnosis and treatment. Two new drug allergy clinics have been
      established in public hospitals, and for the first time in 20 years, Hong Kong
      has its first trainee in adult allergy. The current ratio of allergists per head
      of population has improved slightly from 1:1.46 (in 2014) to 1:1.17 million, but
      it is still low compared to many countries. The Hong Kong community is well
      supported by allergy-related professional societies and patient organisations.
      While the recent developments indicated some progress, Hong Kong remains
      inadequately equipped to take advantage of the new discoveries that may prevent
      allergic diseases and improve public health. There are also 5-fold more
      paediatric allergists than adult allergists per head of population. If this
      unbalance remains uncorrected, continuing care for allergic children as they grow
      into adulthood will be an increasing problem. This review provides
      recommendations to improve allergy service provision and training, including the
      creation of Centres of Excellence in allergy to drive the growth of this
      specialty.

PMID- 29223148
TI  - Exhaled nitric oxide helps discriminating asthmatic children with and without
      positive specific IgE to aeroallergens.
AB  - BACKGROUND: Aeroallergen sensitization may predict higher fractional exhaled
      nitric oxide (FeNO) levels. OBJECTIVE: We evaluate cut-off values of FeNO in
      asthmatic children with and without positive specific immunoglobulin E (IgE) to
      at least one of 5 aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides
      farinae, cat, dog, and cockroach). METHODS: 564 patients with asthma and allergic
      rhinitis (AR) aged 5 to 18 years were enrolled into two groups. Sensitized group
      included 378 children with positive IgE to at least one of 5 inhaled allergens.
      Non-sensitized group included 186 children. Pulmonary function tests, FeNO,
      eosinophil counts, and IgE levels were examined. Patients were divided into
      preschool age (5~6 years old), elementary school children (7~11 years old) and
      adolescents (12~18 years old). RESULTS: In preschool children, FeNO>=15.5 ppb
      differentiates between non-sensitized and sensitized groups. (sensitivity 54.3%;
      specificity 87.5%; positive predictive value (PPV) 86.2%; negative predictive
      value (NPV) 57.1%; area under receiver operating characteristic curve (AUC) 0.72)
      Among elementary school children, the cut-off value of FeNO>=19.5 ppb showed
      sensitivity 66.4%; specificity 85.8%; PPV 90.5%; NPV 55.7%; AUC 0.81. In
      adolescents, FeNO>=27.5 ppb showed sensitivity 60.2%; specificity 85.4%; PPV
      91.2%; NPV 46.1%; AUC 0.76. CONCLUSION: In asthmatic children, aeroallergen
      sensitization appears to contribute to higher FeNO levels than those not
      sensitized. Cut-off values of FeNO which well discriminate asthmatic children
      with and without aeroallergen sensitization should be chose according to
      different ages.

PMID- 29223149
TI  - Accuracy of childhood asthma control test among Thai childhood asthma patients.
AB  - BACKGROUND: The Childhood Asthma Control Test (C-ACT) was developed to assess
      asthma control in children worldwide. A self-administered questionnaire for
      children translated into Thai language was used. OBJECTIVE: To validate the C-ACT
      cut-points for evaluating the level of asthma control among Thai children, using
      the Global Initiative for Asthma (GINA) guideline as a gold standard. METHODS: C
      ACT score, FEV1 and assessment of level of asthma control were recorded at
      baseline, 3-month, 6-month, and 1-year visits among children with asthma.
      Receiver operating characteristic (ROC) curves was used to determine the area
      under the curve (AUC) of C-ACT score for determining the level of asthma control.
      Validity indicators were calculated at different C-ACT cut-points to determine
      those most appropriate for predicting controlled and uncontrolled asthma.
      RESULTS: We enrolled 279 children, 64% males, with mean age 6.87+/-2.4 years. C
      ACT score was significantly correlated with FEV1 at 3-month, 6-month, and 1-year
      visits (p<0.001). The AUC of C-ACT score compared with GINA score were above 80%
      at all visits. The suggested C-ACT score cut-point of controlled asthma was >= 23
      (sensitivity 69.5%, specificity 73.3%, positive predictive value (PPV) 81.2%,
      negative predictive value (NPV) 63.8%); that of uncontrolled asthma was <= 18
      (sensitivity 54.2%, specificity 96.9%, PPV 61.9%, NPV 95.7%). CONCLUSIONS: The
      Thai version of the C-ACT is an accurate, simple, and useful tool for assessing
      asthma control among Thai children. The high AUC suggests that the Thai C-ACT is
      as good as the GINA guideline in predicting asthma control level.

PMID- 29223150
TI  - Modern Approaches for Identification of Modified Nucleotides in RNA.
AB  - This review considers approaches for detection of modified monomers in the RNA
      structure of living organisms. Recently, some data on dynamic alterations in the
      pool of modifications of the key RNA species that depend on external factors
      affecting the cells and physiological conditions of the whole organism have been
      accumulated. The recent studies have presented experimental data on relationship
      between the mechanisms of formation of modified/minor nucleotides of RNA in
      mammalian cells and the development of various pathologies. The development of
      novel methods for detection of chemical modifications of RNA nucleotides in the
      cells of living organisms and accumulation of knowledge on the contribution of
      modified monomers to metabolism and functioning of individual RNA species
      establish the basis for creation of novel diagnostic and therapeutic approaches.
      This review includes a short description of routine methods for determination of
      modified nucleotides in RNA and considers in detail modern approaches that enable
      not only detection but also quantitative assessment of the modification level of
      various nucleotides in individual RNA species.

PMID- 29223151
TI  - The Power and Limitations of Influenza Virus Hemagglutinin Assays.
AB  - Influenza virus hemagglutinins (HAs) are surface proteins that bind to sialic
      acid residues at the host cell surface and ensure further virus internalization.
      Development of methods for the inhibition of these processes drives progress in
      the design of new antiviral drugs. The state of the isolated HA (i.e. combining
      tertiary structure and extent of oligomerization) is defined by multiple factors,
      like the HA source and purification method, posttranslational modifications, pH,
      etc. The HA state affects HA functional activity and significantly impacts the
      results of numerous HA assays. In this review, we analyze the power and
      limitations of currently used HA assays regarding the state of HA.

PMID- 29223152
TI  - Electron Transfer through the Acceptor Side of Photosystem I: Interaction with
      Exogenous Acceptors and Molecular Oxygen.
AB  - This review considers the state-of-the-art on mechanisms and alternative pathways
      of electron transfer in photosynthetic electron transport chains of chloroplasts
      and cyanobacteria. The mechanisms of electron transport control between
      photosystems (PS) I and II and the Calvin-Benson cycle are considered. The
      redistribution of electron fluxes between the noncyclic, cyclic, and pseudocyclic
      pathways plays an important role in the regulation of photosynthesis.
      Mathematical modeling of light-induced electron transport processes is
      considered. Particular attention is given to the electron transfer reactions on
      the acceptor side of PS I and to interactions of PS I with exogenous acceptors,
      including molecular oxygen. A kinetic model of PS I and its interaction with
      exogenous electron acceptors has been developed. This model is based on
      experimental kinetics of charge recombination in isolated PS I. Kinetic and
      thermodynamic parameters of the electron transfer reactions in PS I are
      scrutinized. The free energies of electron transfer between quinone acceptors
      A1A/A1B in the symmetric redox cofactor branches of PS I and iron-sulfur clusters
      FX, FA, and FB have been estimated. The second-order rate constants of electron
      transfer from PS I to external acceptors have been determined. The data suggest
      that byproduct formation of superoxide radical in PS I due to the reduction of
      molecular oxygen in the A1 site (Mehler reaction) can exceed 0.3% of the total
      electron flux in PS I.

PMID- 29223153
TI  - Temperature Dependence of Tryptophan Fluorescence Lifetime in Aqueous Glycerol
      and Trehalose Solutions.
AB  - The temperature dependences of tryptophan fluorescence decay kinetics in aqueous
      glycerol and 1 M trehalose solutions were examined. The fluorescence decay
      kinetics were recorded in the spectral region of 292.5-417.5 nm with nanosecond
      time resolution. The kinetics curves were approximated by the sum of three
      exponential terms, and the spectral distribution (DAS) of these components was
      determined. An antisymbatic course of fluorescence decay times of two (fast and
      medium) components in the temperature range from -60 to +10 degrees C was
      observed. The third (slow) component showed only slight temperature dependence.
      The antisymbatic behavior of fluorescence lifetimes of the fast and medium
      components was explained on the assumption that some of the excited tryptophan
      molecules are transferred from a short-wavelength B-form with short fluorescence
      lifetime to a long-wavelength R-form with an intermediate fluorescence lifetime.
      This transfer occurred in the indicated temperature range.

PMID- 29223154
TI  - Antiinflammatory Effect of Rosiglitazone via Modulation of mRNA Stability of
      Interleukin 10 and Cyclooxygenase 2 in Astrocytes.
AB  - Investigation of molecular mechanisms of proinflammatory stimuli signaling in
      astrocytes is important for understanding their role in pathogenesis of central
      nervous system diseases as well as in functioning of the innate immunity system
      in non-immune cells. Here we show that lipopolysaccharide (LPS) stimulation of
      primary rat astrocytes led to conventional inflammatory response: increase in
      both proinflammatory (tumor necrosis factor, TNFalpha; prostaglandin E2, PGE2)
      and antiinflammatory marker (interleukin 10, IL-10) levels. The protein level of
      cyclooxygenase 2 (COX-2) was also increased. Rosiglitazone strengthened LPS
      induced mRNA expression of COX-2 and IL-10 but not TNFalpha. Rosiglitazone is an
      agonist of nuclear receptor PPARgamma, but its impact on IL-10 expression was not
      influenced by a PPARgamma antagonist, GW9662, suggesting PPARgamma-independent
      effect of rosiglitazone. The degradation of mRNA is one of the steps of
      inflammation regulation and might be affected by small molecules. In experiments
      with actinomycin D, we found that mRNA half-lives of IL-10, COX-2, and TNFalpha
      in naive astrocytes were 70, 44, and 19 min, respectively. LPS stimulation caused
      2-fold increase in IL-10 and COX-2 mRNA decay rates, whereas addition of
      rosiglitazone restored them to the initial level. TNFalpha decay rate was not
      changed by these stimulations. This suggests that mRNA decay rate could be
      regulated by small molecules. Moreover, rosiglitazone could be used as a
      substance stimulating the resolution of inflammation without influence on
      proinflammatory signals. These results open new perspectives in the search for
      inflammation resolution modulators.

PMID- 29223155
TI  - Recombinant Human Erythropoietin with Additional Processable Protein Domains:
      Purification of Protein Synthesized in Escherichia coli Heterologous Expression
      System.
AB  - Three variants of human recombinant erythropoietin (rhEPO) with additional N
      terminal protein domains were obtained by synthesis in an Escherichia coli
      heterologous expression system. These domains included (i) maltose-binding
      protein (MBP), (ii) MBP with six histidine residues (6His) in N-terminal
      position, (iii) s-tag (15-a.a. oligopeptide derived from bovine pancreatic
      ribonuclease A) with N-terminal 6His. Both variants of the chimeric protein
      containing MBP domain were prone to aggregation under nondenaturing conditions,
      and further purification of EPO after the domain cleavage by enterokinase proved
      to be impossible. In the case of 6His-s-tag-EPO chimeric protein, the products
      obtained after cleavage with enterokinase were successfully separated by column
      chromatography, and rhEPO without additional domains was obtained. Results of
      MALDI-TOF mass spectrometry showed that after refolding 6His-s-tag-EPO formed a
      structure similar to that of one of native EPO with two disulfide bonds. Both
      6His-s-tag-EPO and rhEPO without additional protein domains purified after
      proteolysis possessed the same biological activity in vitro in the cell culture.

PMID- 29223156
TI  - Biochemical Properties and Phylogeny of Hydroxypyruvate Reductases from
      Methanotrophic Bacteria with Different C1-Assimilation Pathways.
AB  - In the aerobic methanotrophic bacteria Methylomicrobium alcaliphilum 20Z,
      Methylococcus capsulatus Bath, and Methylosinus trichosporium OB3b, the
      biochemical properties of hydroxypyruvate reductase (Hpr), an indicator enzyme of
      the serine pathway for assimilation of reduced C1-compounds, were comparatively
      analyzed. The recombinant Hpr obtained by cloning and heterologous expression of
      the hpr gene in Escherichia coli catalyzed NAD(P)H-dependent reduction of
      hydroxypyruvate or glyoxylate, but did not catalyze the reverse reactions of D
      glycerate or glycolate oxidation. The absence of the glycerate dehydrogenase
      activity in the methanotrophic Hpr confirmed a key role of the enzyme in
      utilization of C1-compounds via the serine cycle. The enzyme from Ms.
      trichosporium OB3b realizing the serine cycle as a sole assimilation pathway had
      much higher special activity and affinity in comparison to Hpr from Mm.
      alcaliphilum 20Z and Mc. capsulatus Bath assimilating carbon predominantly via
      the ribulose monophosphate (RuMP) cycle. The hpr gene was found as part of gene
      clusters coding the serine cycle enzymes in all sequenced methanotrophic genomes
      except the representatives of the Verrucomicrobia phylum. Phylogenetic analyses
      revealed two types of Hpr: (i) Hpr of methanotrophs belonging to the
      Gammaproteobacteria class, which use the serine cycle along with the RuMP cycle,
      as well as of non-methylotrophic bacteria belonging to the Alphaproteobacteria
      class; (ii) Hpr of methylotrophs from Alpha- and Betaproteobacteria classes that
      use only the serine cycle and of non-methylotrophic representatives of
      Betaproteobacteria. The putative role and origin of hydroxypyruvate reductase in
      methanotrophs are discussed.

PMID- 29223157
TI  - Self-Organization of Recombinant Membrane Porin OmpF from Yersinia
      pseudotuberculosis in Aqueous Environments.
AB  - Recombinant porin OmpF (an integral protein of bacterial outer membrane) from
      Yersinia pseudotuberculosis was synthesized in Escherichia coli cells as
      inclusion bodies. By combining the methods of anion-exchange and gel filtration
      chromatographies, recombinant OmpF (rOmpF) was isolated as an individual protein
      in its denatured state, and its characteristic properties (molecular mass, N
      terminal amino acid sequence, and hydrodynamic radius of the protein in 8 M urea
      solution) were determined. According to the data of gel filtration, dynamic light
      scattering, optical spectroscopy, and binding of the hydrophobic fluorescent
      probe 8-anilino-1-naphthalenesulfonic acid, the rOmpF is fully unfolded in 8 M
      urea and exists in random coil conformation. In aqueous solutions, rOmpF
      undergoes conformational changes, reversible self-association, and aggregation.
      When transferred from 8 M urea into water, PBS (containing 0.15 M NaCl, pH 7.4),
      or buffer containing 0.8 M urea (pH 8.0), fully unfolded rOmpF forms relatively
      compact monomeric intermediates prone to self-association with formation of
      multimers. The oligomeric intermediates have high content of native protein-like
      secondary structure and pronounced tertiary structure. In acidic media (pH 5.0,
      close to the protein isoelectric point), rOmpF undergoes rapid irreversible
      aggregation. Therefore, we found that medium composition significantly affects
      both porin folding and processes of its self-association and aggregation.

PMID- 29223158
TI  - Salusin-alpha Attenuates Inflammatory Responses in Vascular Endothelial Cells.
AB  - Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have
      a critical role in acceleration or suppression of disease. Salusin-alpha presents
      a new class of bioactive peptides that can have anti-atherogenic properties.
      Therefore, the effects of salusin-alpha on the expression of some pro- and anti
      inflammatory cytokines and on TNF-alpha-induced inflammatory responses in human
      umbilical vein endothelial cells (HUVECs) were examined. The involvement of the
      NF-kappaB pathway in effects of salusin-alpha in HUVECs was checked using Bay 11
      7082 as an NF-kappaB inhibitor. The mRNA expression of pro-inflammatory cytokines
      including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was
      assessed by real-time PCR. The protein levels of cytokines were measured by the
      ELISA method. Salusin-alpha suppressed both mRNA and protein expression of pro
      inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in
      HUVECs. Salusin-alpha suppressed TNF-alpha-induced inflammatory responses in
      HUVECs. The down-regulatory or up-regulatory effects of salusin-alpha on
      expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our
      findings indicate anti-inflammatory effects of salusin-alpha and suggest a novel
      peptide-based therapeutic strategy for atherosclerosis.

PMID- 29223159
TI  - Factors beyond Enolase 2 and Mitochondrial Lysyl-tRNA Synthetase Precursor Are
      Required for tRNA Import into Yeast Mitochondria.
AB  - In yeast, the import of tRNALys with CUU anticodon (tRK1) relies on a complex
      mechanism where interaction with enolase 2 (Eno2p) dictates a deep conformational
      change of the tRNA. This event is believed to mask the tRNA from the cytosolic
      translational machinery to re-direct it towards the mitochondria. Once near the
      mitochondrial outer membrane, the precursor of the mitochondrial lysyl-tRNA
      synthetase (preMsk1p) takes over enolase to carry the tRNA within the
      mitochondrial matrix, where it is supposed to participate in translation
      following correct refolding. Biochemical data presented in this report focus on
      the role of enolase. They show that despite the inability of Eno2p alone to form
      a complex with tRK1, mitochondrial import can be recapitulated in vitro using
      fractions of yeast extracts sharing either recombinant or endogenous yeast Eno2p
      as one of the main components. Taken together, our data suggest the existence of
      a protein complex containing Eno2p that is involved in RNA mitochondrial import.

PMID- 29223160
TI  - Cathelicidin LL37 Promotes Epithelial and Smooth-Muscle-Like Differentiation of
      Adipose-Derived Stem Cells through the Wnt/beta-Catenin and NF-kappaB Pathways.
AB  - Ureter reconstruction is a difficult procedure in urology. Adipose-derived stem
      cells (ADSCs), along with multipotency and self-renewal capacity, are a preferred
      choice for tissue engineering-based ureteral reconstruction. We explored the
      synergic role of cathelicidin LL37 (LL37) in epithelial and smooth-muscle-like
      differentiation. ADSCs were separated from adipose tissues of mouse and
      characterized by flow cytometry. The ADSCs were then stably transfected with pGC
      FU-GFP (pGC) or pGC containing full-length LL37 (pGC-LL37), respectively. Cell
      viability and apoptosis were respectively estimated in the stably transfected
      cells and non-transfected cells. Then, qRT-PCR and Western blot analysis were
      used for determinations of epithelial marker expressions after induction by all
      trans retinoic acid as well as smooth-muscle-like marker expressions after
      induction by transforming growth factor-beta1. Then, possibly involved signaling
      pathways and extracellular expression of LL37 were detected. Cell viability and
      apoptosis were not changed after LL37 overexpression. Expression levels of
      epithelial and smooth-muscle-like markers were significantly upregulated by LL37
      overexpression. Moreover, expressions of key kinases involved in the Wnt/beta
      catenin pathway as well as epithelial marker were upregulated by the LL37
      overexpression, while it was reversed by Wnt/beta-catenin inhibitor. Likewise,
      expressions of key kinases involved in the nuclear factor kappaB (NF-kappaB)
      pathway as well as smooth-muscle-like markers were upregulated by LL37
      overexpression, which was reversed by NF-kappaB inhibitor. LL37 was found in the
      culture medium. LL37, which could be released into the medium, had no impact on
      cell proliferation and apoptosis of ADSCs. However, LL37 promoted epithelial and
      smooth-muscle-like differentiation through activating the Wnt/beta-catenin and NF
      kappaB pathways, respectively.

PMID- 29223161
TI  - Cell-Free Expression, Purification, and Characterization of the Functional beta2
      Adrenergic Receptor for Multianalyte Detection of beta-Agonists.
AB  - Large-scale expression of beta2-adrenergic receptor (beta2-AR) in functional form
      is necessary for establishment of receptor assays for detecting illegally abused
      beta-adrenergic agonists (beta-agonists). Cell-based heterologous expression
      systems have manycritical difficulties in synthesizing this membrane protein,
      such as low protein yields and aberrant folding. To overcome these challenges,
      the main objective of the present work was to synthesize large amounts of
      functional beta2-AR in a cell-free system based on Escherichia coli extracts. A
      codon-optimized porcine beta2-AR gene (codon adaptation index: 0.96) suitable for
      high expression in E. coli was synthesized and transcribed to the cell-free
      system, which contributed to increase the expression up to 1.1 mg/ml. After
      purification using Ni-affinity chromatography, the bioactivity of the purified
      receptor was measured by novel enzyme-linked receptor assays. It was determined
      that the relative affinities of the purified beta2-AR for beta-agonists in
      descending order were as follows: clenbuterol > salbutamol > ractopamine.
      Moreover, their IC50 values were 45.99, 60.38, and 78.02 ug/liter, respectively.
      Although activity of the cell-free system was slightly lower than activity of
      systems based on insect and mammalian cells, this system should allow production
      of beta2-AR in bulk amounts sufficient for the development of multianalyte
      screening methods for detecting beta-agonist residues.

PMID- 29223162
TI  - Spectral-Kinetic Analysis of Recombination Reaction of Heme Centers of bd-Type
      Quinol Oxidase from Escherichia coli with Carbon Monoxide.
AB  - Recombination of the isolated, fully reduced bd-type quinol oxidase from
      Escherichia coli with carbon monoxide was studied by pulsed absorption
      spectrophotometry with microsecond time resolution. Analysis of the kinetic
      phases of recombination was carried out using the global analysis of
      multiwavelength kinetic data ("Global fitting"). It was found that the unresolved
      photodissociation of CO is followed by a stepwise (with four phases)
      recombination with characteristic times (tau) of about 20 us, 250 us, 1.1 ms, and
      24 ms. The 20-us phase most likely reflects bimolecular recombination of CO with
      heme d. Two subsequent kinetic transitions, with tau ~ 250 us and 1.1 ms, were
      resolved for the first time. It is assumed that the 250-us phase is heterogeneous
      and includes two different processes: recombination of CO with ~7% of heme b595
      and transition of heme d from a pentacoordinate to a transient hexacoordinate
      state in this enzyme population. The 24-ms transition probably reflects a return
      of heme d to the pentacoordinate state in the same protein fraction. The 1.1-ms
      phase can be explained by recombination of CO with ~15% of heme b558. Possible
      models of interaction of CO with different heme centers are discussed.

PMID- 29223163
TI  - Neuroprotective Properties of Endocannabinoids N-Arachidonoyl Dopamine and N
      Docosahexaenoyl Dopamine Examined in Neuronal Precursors Derived from Human
      Pluripotent Stem Cells.
AB  - Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and
      N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells
      differentiated from human induced pluripotent stem cells and subjected to
      oxidative stress. Both compounds exerted neuroprotective activity, which was
      enhanced by elevating the concentration of the endocannabinoids within the 0.1-10
      uM range. However, both agents at 10 uM concentration showed a marked toxic
      effect resulting in death of ~30% of the cells. Finally, antagonists of
      cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system
      did not hamper the neuroprotective effects of these endocannabinoids.

PMID- 29223164
TI  - The Mitochondrial Genome of the Moss Brachythecium rivulare (Hypnales,
      Brachytheciaceae).
AB  - The mitochondrial genome of the pleurocarpous moss Brachythecium rivulare has
      been sequenced and annotated. The genome consists of 104,460 base pairs and has
      approximately the same gene set and organization as other bryophyte mitogenomes.
      Whole mitochondrial genome comparison between B. rivulare and Physcomitrella
      patens, Tetraphis pellucida, Anomodon rugelii, and Anomodon attenuatus was
      performed. The primary cause of bryophyte mitochondrial gene length variation was
      found to be numerous indels in the introns. Bryophyte mitochondrial gene
      conservation level was estimated, and it was in a good congruence with the
      overall phylogeny of bryophytes with the percentage of mitogenome similarity
      being proportional to the age estimated by phylochronologic analysis. Annotation
      discrepancies in the analyzed mitogenome sequences were identified. The simple
      sequence repeat (SSR) content was evaluated, and candidate sites of RNA editing
      were predicted in the B. rivulare mitochondrial genome.

PMID- 29223165
TI  - Role of microRNA in Development of Instability of Atherosclerotic Plaques.
AB  - MicroRNAs are small noncoding single-stranded RNAs that regulate gene expression.
      Today, we see an increasing number of studies highlighting the important role of
      microRNAs in the development and progression of cardiovascular diseases caused by
      atherosclerotic lesions of arteries. We review the available scientific data on
      association of the expression of these biomolecules with instability of
      atherosclerotic plaques in animal models and humans. We made special emphasis on
      miR-21, -100, -127, -133, -143/145, -221/222, and -494 because they were analyzed
      in more than one study. We discuss the possibility of microRNAs using in the
      diagnosis and therapy of atherosclerosis and its complications.

PMID- 29223166
TI  - Protein Poly(ADP-ribosyl)ation System: Changes in Development and Aging as well
      as due to Restriction of Cell Proliferation.
AB  - It is well known that the number of dividing cells in an organism decreases with
      age. The average rate of cell division in tissues and organs of a mature organism
      sharply decreases, which is probably a trigger for accumulation of damage leading
      to disturbance of genome integrity. This can be a cause for the development of
      many age-related diseases and appearance of phenotypic and physiological signs of
      aging. In this connection, the protein poly(ADP-ribosyl)ation system, which is
      activated in response to appearance of various DNA damage, attracts great
      interest. This review summarizes and analyzes data on changes in the poly(ADP
      ribosyl)ation system during development and aging in vivo and in vitro, and due
      to restriction of cell proliferation. Special attention is given to
      methodological aspects of determination of activity of poly(ADP-ribose)
      polymerases (PARPs). Analysis of relevant publications and our own data has led
      us to the conclusion that PARP activity upon the addition of free DNA ends (in
      this review referred to as stimulated PARP activity) is steadily decreasing with
      age. However, the dynamics of PARP activity measured without additional
      activation of the enzyme (in this review referred to as unstimulated activity)
      does not have such a clear trend: in many studies, the presented differences are
      statistically non-significant, although it is well known that the number of
      unrepaired DNA lesions steadily increases with aging. Apparently, the cell has
      additional regulatory systems that limit its own capability of reacting to DNA
      damage. Special attention is given to the influence of the cell proliferative
      status on PARP activity. We have systematized and analyzed data on changes in
      PARP activity during development and aging of an organism, as well as data on
      differences in the dynamics of this activity in the presence/absence of
      additional stimulation and on cellular processes that are associated with
      activation of these enzymes. Moreover, data obtained in different models of
      cellular aging are compared.

PMID- 29223167
TI  - Editorial: New Horizons in Controlled Ovarian Stimulation.

PMID- 29223168
TI  - Serious gastric perforation after second stereotactic body radiotherapy for
      peripheral lung cancer that recurred after initial stereotactic body
      radiotherapy: a case report.
AB  - BACKGROUND: In recent reports, re-irradiation with stereotactic body radiotherapy
      for lung tumors in patients previously treated with thoracic radiation therapy
      resulted in several serious toxicities. Serious non-lung toxicities were observed
      mostly in patients with central tumors, but we experienced a case of fatal
      gastric perforation after a second stereotactic body radiotherapy in a patient
      with a peripheral lung tumor. CASE PRESENTATION: An 83-year-old Asian man was
      diagnosed with T2N0M0 lung cancer in the form of squamous cell carcinoma in the
      lower lobe of his left lung. He was treated with stereotactic body radiotherapy
      of 40 Gy in 4 fractions and the tumor decreased in size in partial response. The
      local tumor recurred 8 months after the first stereotactic body radiotherapy, and
      he was re-irradiated with a second stereotactic body radiotherapy of 50 Gy in 4
      fractions. A Sengstaken-Blakemore tube was inserted below his diaphragm by
      laparoscopic surgery before the second stereotactic body radiotherapy in order to
      reduce the stomach dose by keeping his stomach apart from the tumor. Two months
      after the second stereotactic body radiotherapy, he developed fatal gastric
      perforation and gastropleural fistula penetrating his diaphragm. CONCLUSIONS: To
      the best of our knowledge, this is the first report about a gastric perforation
      after stereotactic body radiotherapy for lung tumors and it warns of serious
      complication of stereotactic body radiotherapy in not only centrally located but
      also peripherally located tumors like in this case.

PMID- 29223169
TI  - An overview on Leishmania (Mundinia) enriettii: biology, immunopathology, LRV and
      extracellular vesicles during the host-parasite interaction.
AB  - One of the Leishmania species known to be non-infective to humans is Leishmania
      (Mundinia) enriettii whose vertebrate host is the guinea pig Cavia porcellus. It
      is a good model for cutaneous leishmaniasis, chemotherapeutic and molecular
      studies. In the last years, an increased interest has emerged concerning the L.
      (Mundinia) subgenus after the finding of Leishmania (M.) macropodum in Australia
      and with the description of other new/putative species such as L. (M.)
      martiniquensis and 'L. (M.) siamensis'. This review focused on histopathology,
      glycoconjugates and innate immunity. The presence of Leishmania RNA virus and
      shedding of extracellular vesicles by the parasite were also evaluated.

PMID- 29223170
TI  - Changes in job strain and subsequent weight gain: a longitudinal study, based on
      the Danish Nurse Cohort.
AB  - OBJECTIVE: Obesity as well as job strain is increasing, and job strain might
      contribute to weight gain. The objective of the current study was to examine
      associations between longitudinal alterations in the components of job strain and
      subsequent weight gain. DESIGN: The study was designed as a prospective cohort
      study with three questionnaire surveys enabling measurement of job-strain
      alterations over 6 years and subsequent measurements of weight gain after further
      10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were
      measured as job busyness and speed, and control as amount of influence. SETTING:
      Employed nurses in Denmark. SUBJECTS: We included a sub-sample of 6188 female
      nurses from the Danish Nurse Cohort, which consisted of the nurses who
      participated in surveys in 1993, 1999 and 2009. RESULTS: A linear trend in weight
      gain was seen in nurses who were often busy in 1999 between those who were rarely
      v. sometimes v. often busy in 1993 (P=0.03), with the largest weight gain in
      individuals with sustained high busyness in both years. Loss of influence between
      1993 and 1999 was associated with larger subsequent weight gain than sustained
      high influence (P=0.003) or sustained low influence (P=0.02). For speed, no
      associations were found. CONCLUSIONS: Busyness, speed and influence differed in
      their relationship to subsequent weight gain. A decrease in job influence and a
      sustained burden of busyness were most strongly related to subsequent weight
      gain. Focus on job strain reduction and healthy diet is essential for public
      health.

PMID- 29223171
TI  - Caregiver burden, sleep quality, depression, and anxiety in dementia caregivers:
      a comparison of frontotemporal lobar degeneration, dementia with Lewy bodies, and
      Alzheimer's disease.
AB  - : ABSTRACTBackground:Very few recent studies are available that compare caregiver
      burden, sleep quality, and stress in caregivers of different types of dementia.
      We aimed to investigate caregiver burden, sleep quality, and stress in caregivers
      of patients with frontotemporal lobar degeneration and dementia with Lewy bodies,
      as compared with caregivers of patients with Alzheimer's disease. METHODS: This
      study was carried out from March 2011 to January 2014. In total, 492 dyads of
      patient and caregiver (frontotemporal lobar degeneration, n = 131; dementia with
      Lewy bodies, n = 36; Alzheimer's disease, n = 325) participated in this study. We
      compared patients with respect to the Neuropsychiatric Inventory and caregivers
      with respect to the Zarit Caregiver Burden Interview, Pittsburgh Sleep Quality
      Index, Patient Health Questionnaire-9, and Generalized Anxiety Disorder scale.
      RESULTS: Frontotemporal lobar degeneration and dementia with Lewy bodies patients
      presented significantly more neuropsychiatric symptoms compared to Alzheimer's
      disease patients. Caregivers of frontotemporal lobar degeneration and dementia
      with Lewy bodies patients experienced significantly more burden compared to
      Alzheimer's disease caregivers. Furthermore, among caregivers of both
      frontotemporal lobar degeneration and dementia with Lewy bodies patients burden
      was predicted by the neuropsychiatric symptoms, PHQ-9 scores, and GAD-7 scores.
      CONCLUSIONS: The frequency and severity of behavioral disturbances in patient and
      caregiver stress accounted for the increased caregiver burden, which suggests
      that frontotemporal lobar degeneration and dementia with Lewy bodies caregivers
      should receive more support than is currently available.

PMID- 29223172
TI  - Association between the use of benzodiazepines and opioids with the risk of falls
      and hip fractures in older adults.
AB  - : ABSTRACTBackground:To determine the association between the use of opioids and
      benzodiazepines and the risk of falls with hip fracture in populations older than
      65 years in Colombia. METHODS: A case-control study with patients older than 65
      years with diagnosis of hip fracture. Two controls were obtained per case. The
      drugs dispensed in the previous 30 days were identified. Sociodemographic,
      diagnostic, pharmacological (opioids and benzodiazepines), and polypharmacy
      variables were analyzed. A logistic regression model was used to analyze the risk
      of fall with hip fracture while using these drugs. RESULTS: We included 287
      patients with hip fractures and 574 controls. There was a female predominance
      (72.1%) and a mean age of 82.4 +/- 8.0 years. Of the patients, 12.7% had been
      prescribed with opioids and 4.2% with benzodiazepines in the previous month. The
      adjusted multivariate analysis found that using opioids (OR:4.49; 95%CI:2.72
      7.42) and benzodiazepines (OR:3.73; 95%CI:1.60-8.70) in the month prior to the
      event was significantly associated with a greater probability of suffering a fall
      with hip fracture. CONCLUSIONS: People who are taking opioids and benzodiazepines
      have increased risk for hip fracture in Colombia. Strategies to educate
      physicians regarding the pharmacology of older adults should be strengthened.

PMID- 29223173
TI  - The Worried Well? Characteristics of Cognitively Normal Patients Presenting to a
      Rural and Remote Memory Clinic.
AB  - INTRODUCTION: In an effort to better understand why cognitively normal patients
      were referred to a memory clinic, we sought to identify features of "worried
      well" patients to better identify those more likely to be cognitively normal.
      METHODS: In total, 375 consecutive patients referred by primary care
      practitioners to a Rural and Remote Memory Clinic were categorized into two
      groups based on their neurologic diagnosis, "worried well" (cognitively normal,
      N=81) or "other" (patients with any neurologic diagnosis, N=294). Data collected
      included: age, sex, years of formal education, Mini-Mental Status Examination
      score from initial visit, Center for Epidemiologic Studies Depression Scale
      score, Self-Rating of Memory Scale, alcohol consumption, marital status, hours
      per week of work, past medical history, sleep concerns, and family history of
      memory concerns. The two groups were compared using t-tests and chi2 tests. The
      same comparison was done between the same set of "worried well" patients
      (cognitively normal, N=81) and the subgroup of patients with a diagnosis of
      Alzheimer's disease (N=146) from the "other" group. RESULTS: Significant
      differences included younger age, more formal education, more frequently having
      previous psychiatric diagnosis and more self-reported alcohol consumption in the
      "worried well" group. The "worried well" and "Alzheimer's disease" comparison had
      the same significant differences as the "worried well" and "other" comparison.
      CONCLUSION: We observed a pattern of differences unfold between the "worried
      well" patients and those with cognitive disease. No one variable was
      pathognomonic of a "worried well" patient. However, taking all the above into
      account when evaluating a patient may help clinically.

PMID- 29223174
TI  - Relationships between the neighborhood environment and depression in older
      adults: a systematic review and meta-analysis.
AB  - : ABSTRACTBackground:While depression is a growing public health issue, the
      percentage of individuals with depression receiving treatment is low. Physical
      and social attributes of the neighborhood may influence the level of depressive
      symptoms and the prevalence of depression in older adults. METHODS: This review
      systematically examined the literature on neighborhood environmental correlates
      of depression in older adults. Findings were analyzed according to three
      depression outcomes: depressive symptoms, possible depression, and clinical
      depression. Based on their description in the article, environmental variables
      were assigned to one of 25 categories. The strength of evidence was statistically
      quantified using a meta-analytical approach with articles weighted for sample
      size and study quality. Findings were summarized by the number of positive,
      negative, and statistically non-significant associations by each combination of
      environmental attribute - depression outcome and by combining all depression
      outcomes. RESULTS: Seventy-three articles met the selection criteria. For all
      depression outcomes combined, 12 of the 25 environmental attribute categories
      were considered to be sufficiently studied. Three of these, neighborhood socio
      economic status, collective efficacy, and personal/crime-related safety were
      negatively associated with all depression outcomes combined. Moderating effects
      on associations were sparsely investigated, with 52 articles not examining any.
      Attributes of the physical neighborhood environment have been understudied.
      CONCLUSION: This review provides support for the potential influence of some
      neighborhood attributes on population levels of depression. However, further
      research is needed to adequately examine physical attributes associated with
      depression and moderators of both social and physical neighborhood environment
      attribute - depression outcome associations.

PMID- 29223175
TI  - The assessment of anxiety in aged care residents: a systematic review of the
      psychometric properties of commonly used measures.
AB  - : ABSTRACTBackground:Assessing anxiety among residential aged care facility
      (RACF) residents is challenging, and it cannot be assumed that valid and reliable
      measures used within the community are also appropriate for this setting. This
      review systematically examined the literature to identify which anxiety measures
      were most commonly used with older adults in RACFs, and determine whether
      psychometric data support their use within this population. METHODS: Using the
      PRISMA guidelines, five electronic databases were searched using key terms and
      subject headings. The search was limited to literature published in English.
      Eligible studies utilized an anxiety measure to assess anxiety symptoms among
      RACF residents. Based on the findings of this search, a critical review of the
      research into the reliability, validity, and administrative and respondent burden
      of the most commonly used measures (i.e. used in four or more studies) was
      conducted. RESULTS: In total, 1,771 articles were identified, with 50 studies
      included in this review. Overall, 22 measures were used, with the majority of
      studies utilizing a clinician-administered or self-report measure. The RAID,
      HADS, STAI, and GAI were the most commonly used measures. While overall there is
      a lack of research and consensus into the psychometric properties of these
      measures within RACFs, strongest evidence of reliability and validity was found
      for the GAI. CONCLUSION: Commonly used measures of anxiety within aged care
      populations are not well validated for this complex subsample of older adults.
      Strengths and weaknesses of each measure with regards to their usefulness in aged
      care settings are discussed, with future research areas highlighted.

PMID- 29223176
TI  - The Influence of Exposure to Natural Disasters on Depression and PTSD Symptoms
      among Firefighters.
AB  - : Introduction Firefighters represent an important population for understanding
      the consequences of exposure to potentially traumatic stressors.
      Hypothesis/Problem The researchers were interested in the effects of pre
      employment disaster exposure on firefighter recruits' depression and
      posttraumatic stress disorder (PTSD) symptoms during the first three years of
      fire service and hypothesized that: (1) disaster-exposed firefighters would have
      greater depression and PTSD symptoms than non-exposed overall; and (2) depression
      and PTSD symptoms would worsen over years in fire service in exposed
      firefighters, but not in their unexposed counterparts. METHODS: In a baseline
      interview, 35 male firefighter recruits from seven US cities reported lifetime
      exposure to natural disaster. These disaster-exposed male firefighter recruits
      were matched on age, city, and education with non-exposed recruits. RESULTS: A
      generalized linear mixed model revealed a significant exposure*time interaction
      (e coef =1.04; P<.001), such that depression symptoms increased with time for
      those with pre-employment disaster exposure only. This pattern persisted after
      controlling for social support from colleagues (e coefficient=1.05; P<.001),
      social support from families (e coefficient=1.04; P=.001), and on-the-job trauma
      exposure (coefficient=0.06; e coefficient=1.11; P<.001). Posttraumatic stress
      disorder symptoms did not vary significantly between exposure groups at baseline
      (P=.61). CONCLUSION: Depression symptoms increased with time for those with pre
      employment disaster exposure only, even after controlling for social support.
      Posttraumatic stress disorder symptoms did not vary between exposure groups.
      Pennington ML , Carpenter TP , Synett SJ , Torres VA , Teague J , Morissette SB ,
      Knight J , Kamholz BW , Keane TM , Zimering RT , Gulliver SB . The influence of
      exposure to natural disasters on depression and PTSD symptoms among firefighters.
      Prehosp Disaster Med. 2018;33(1):102-108.

PMID- 29223177
TI  - Well-being and distress of patients with Parkinson's disease: a comparative
      investigation.
AB  - BACKGROUND: Psychological resources, such as psychological well-being (PWB) and
      life satisfaction (LS) can aid individuals suffering from chronic illnesses to
      cope with their illness. The aim of this study was to investigate PWB, LS,
      quality of life (QoL), and distress in patients with Parkinson's disease (PD) and
      to compare them with healthy controls. METHODS: One hundred and thirteen
      individuals were recruited. Fifty of the participants suffered from PD, while 53
      individuals reported other non-neurological diseases. PD patients were assessed
      through medical routine examinations. All participants had to be devoid of severe
      cognitive impairment. They were administered self-report questionnaires to
      measure PWB, LS, QoL, and distress. A cross-sectional comparative design was
      applied. RESULTS: PD patients reported higher general PWB than controls with the
      exception of the autonomy subscale where the PD patients scored lower. However,
      they also reported higher distress (anxiety, depression, somatic symptoms, and
      hostility-irritability), lower LS, and poorer QoL compared to controls. In
      regressive models, general PWB and LS were significantly correlated to the
      presence of PD, to its functional impairments, and not to other socio-demographic
      variables. CONCLUSIONS: Findings confirmed previous literature on other
      neurological conditions, showing that PD may be associated with greater
      psychological distress, lower levels of LS and QoL. At the same time, PD patients
      may preserve their PWB, which is a protective factor for mental and physical
      health. The presence of these psychological resources is inversely related to
      functional impairments. Future studies should better investigate the pattern of
      PWB in PD.

PMID- 29223178
TI  - Relative influence of dietary protein and energy contents on lysine requirements
      and voluntary feed intake of rainbow trout fry.
AB  - The effect of dietary digestible protein (DP) and/or digestible energy (DE)
      levels on lysine (Lys) requirements, Lys utilisation efficiency and voluntary
      feed intake (VFI) were studied in rainbow trout fry when Lys was the first
      limiting indispensable amino acid or in excess in the diet. Two trials were
      conducted at 11.6 degrees C with eighty-one experimental diets, containing 280 g
      DP/kg DM (low protein (LP), trial 1), 600 g DP/kg DM (high protein (HP), trial 1)
      or 440 g DP/kg DM (medium protein (MP), trial 2), 17 MJ DE/kg (low energy (LE)),
      19.5 MJ DE/kg (medium energy (ME)) or 22 MJ DE/kg (high energy (HE)), and nine
      Lys levels from deeply deficient to large excess (2.3-36 g/kg DM). Each diet was
      given to apparent satiety to one group of fifty fry (initial body weight 0.85 g)
      for 24 (MP diets, trial 2) or 30 (LP and HP diets, trial 1) feeding days. Based
      on N gain data fitted with the broken-line model, the relative Lys requirement
      was significantly different with the dietary DP level, from 13.3-15.7 to 22.9
      26.5 g/kg DM for LP and HP diets, respectively, but did not significantly change
      with the DE level for a same protein level. The Lys utilisation efficiency for
      protein growth above maintenance was constant across diets, suggesting no effect
      of either dietary DE or DP levels. In Lys excess, the VFI was markedly decreased
      by the DP level but not by the extra DE supply. Our results suggest that the
      relative Lys need is best expressed in terms of percentage of protein content for
      optimum fish feed formulation, at least in rainbow trout fry.

PMID- 29223179
TI  - Intra- and inter-specific variation in alarm pheromone produced by Solenopsis
      fire ants.
AB  - Some fire ants of the genus Solenopsis have become invasive species in the
      southern United States displacing native species by competition. Although the
      displacement pattern seems clear, the mechanisms underlying competitive advantage
      remain unclear. The ability of ant workers to produce relatively larger amount of
      alarm pheromone may correspond to relative greater fitness among sympatric fire
      ant species. Here we report on quantitative intra-specific (i.e. inter-caste) and
      inter-specific differences of alarm pheromone component, 2-ethyl-3,6
      dimethylpyrazine (2E36DMP), for several fire ant species. The alarm pheromone
      component was extracted by soaking ants in hexane for 48 h and subsequently
      quantified by gas chromatography-mass spectrometry at single ion monitoring mode.
      Solenopsis invicta workers had more 2E36DMP than male or female alates by
      relative weight; individual workers, however, contained significantly less
      pyrazine. We thus believe that alarm pheromones may serve additional roles in
      alates. Workers of Solenopsis richteri, S. invicta, and hybrid (S. richteri * S.
      invicta) had significantly more 2E36DMP than a native fire ant species,
      Solenopsis geminata. The hybrid fire ant had significantly less 2E36DMP than the
      two parent species, S. richteri and S. invicta. It seems likely that higher alarm
      pheromone content may have favored invasion success of exotic fire ants over
      native species. We discuss the potential role of inter-specific variation in
      pyrazine content for the relationship between the observed shifts in the spatial
      distributions of the three exotic fire ant species in southern United States and
      the displacement of native fire ant species.

PMID- 29223181
TI  - Reduced cardiotoxicity and increased oral efficacy of artemether polymeric
      nanocapsules in Plasmodium berghei-infected mice.
AB  - Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability
      are the major limiting factors for its use to treat malaria. The purposes of this
      work were to study free-ATM and ATM-loaded poly-epsilon-caprolactone nanocapules
      (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice.
      ATM-NC was obtained by interfacial polymer deposition and ATM was associated with
      polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6
      uninfected or P. berghei-infected mice received, by oral route twice daily/4
      days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at
      doses 40, 80 or 120 mg kg-1. Electrocardiogram (ECG) lead II signal was obtained
      before and after treatment. For ATM efficacy evaluation, female P. berghei
      infected mice were treated the same way. ATM-NC improved antimalarial in vivo
      efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc
      intervals prolongation. ATM-NC (120 mg kg-1) given to uninfected mice reduced QT
      and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM.
      ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28
      and 27%, respectively. For the first time, the study showed a nanocarrier
      reducing cardiotoxicity of ATM given by oral route and it was more effective
      against P. berghei than free-ATM as monotherapy.

PMID- 29223180
TI  - The relationship between gait dynamics and future cognitive decline: a
      prospective pilot study in geriatric patients.
AB  - : ABSTRACTBackground:Walking ability recently emerged as a sub-clinical marker of
      cognitive decline. Hence, the relationship between baseline gait and future
      cognitive decline was examined in geriatric patients. Because a "loss of
      complexity" (LOC) is a key phenomenon of the aging process that exhibits in
      multiple systems, we propose the idea that age- and cognition-related LOC may
      also become manifested in gait function. The LOC theory suggests that even
      healthy aging is associated with a (neuro)physiological breakdown of system
      elements that causes a decline in variability and an overall LOC. We used
      coordination dynamics as a conceptual framework and hypothesized that a LOC is
      reflected in dynamic gait outcomes (e.g. gait regularity, complexity, stability)
      and that such outcomes could increase the specificity of the gait-cognition link.
      METHODS: 19 geriatric patients (age 80.0+/-5.8) were followed for 14.4+/-6.6
      months. An iPod collected three-dimensional (3D) trunk accelerations while
      patients walked for 3 minutes. Cognition was evaluated with the Mini-Mental State
      Examination (MMSE) and the Seven-Minute screen (7MS) test. The Reliable Change
      Index (RCI) quantified the magnitude of cognitive change. Spearman's Rho
      coefficients (rho) indexed correlations between baseline gait and future
      cognitive change. RESULTS: Seven patients showed reliable cognitive decline
      ("Cognitive Decline" group), and 12 patients remained cognitively stable
      ("Cognitive Stable" group) over time. Future cognitive decline was correlated
      with a more regular (rho = 0.579*) and predictable (rho = 0.486*) gait pattern,
      but not with gait speed. CONCLUSIONS: The increase in gait regularity and
      predictability possibly reflects a LOC due to age- and cognition-related
      (neuro)physiological decline. Because dynamic versus traditional gait outcomes
      (i.e. gait speed and (variability of) stride time) were more strongly correlated
      with future cognitive decline, the use of wearable sensors in predicting and
      monitoring cognitive and physical health in vulnerable geriatric patients can be
      considered promising. However, our results are preliminary and do require
      replication in larger cohorts.

PMID- 29223182
TI  - A randomized controlled trial examining the impact of aged care residents'
      written life-stories on aged care staff knowledge and attitudes.
AB  - : ABSTRACTBackground:The unprecedented increase in the number of older adults
      moving into aged care facilities has created a challenge for quality person
      centered care service provision. This study examined the impact of written life
      stories on knowledge and attitudes of care staff about the residents when
      compared to usual file notes. METHODS: A randomized controlled study was carried
      out with 40 staff working in an aged care residential facility. Staff were
      randomly assigned to a control condition, in which they read file notes (n = 21)
      or to an experimental condition, in which they read life stories (n = 19) about
      residents who they knew, and completed the Knowledge of Resident Scale (KRS)
      before and after their assigned reading. RESULTS: A main effect for time was
      found for eight of the ten questions on the KRS, suggesting that irrespective of
      whether a participant read life stories or file notes, there was a significantly
      positive impact on knowledge and attitudes toward residents. However,
      significantly greater improvement was shown for one item on the KRS in the
      experimental condition when compared to the control condition, indicating that
      historical knowledge of residents was greater when staff read life stories than
      when they read file notes, F (1,38) = 6.50, p = 0.02. CONCLUSION: These results
      provide preliminary evidence that knowledge and attitudes of care staff can
      increase about the residents for whom they care following reading file notes and
      life stories. The increase is similar, except in the area of historical
      information, where it is greater for the group who read life stories.

PMID- 29223183
TI  - Conversion between Addenbrooke's Cognitive Examination III and Mini-Mental State
      Examination.
AB  - : ABSTRACTBackground:We aim to provide a conversion between Addenbrooke's
      Cognitive Examination III (ACE-III) and Mini-Mental State Examination (MMSE)
      scores, to predict the MMSE result based on ACE-III, thus avoiding the need for
      both tests, and improving their comparability. METHODS: Equipercentile equating
      method was used to elaborate a conversion table using a group of 400 participants
      comprising healthy controls and Alzheimer's disease (AD) patients. Then,
      reliability was assessed in a group of 100 healthy controls and patients with AD,
      52 with primary progressive aphasia and 22 with behavioral variant frontotemporal
      dementia. RESULTS: The conversion table between ACE-III and MMSE denoted a high
      reliability, with intra-class correlation coefficients of 0.940, 0.922, and 0.902
      in the groups of healthy controls and AD, behavioral variant frontotemporal
      dementia, and primary progressive aphasia, respectively. CONCLUSION: Our
      conversion table between ACE-III and MMSE suggests that MMSE may be estimated
      based on the ACE-III score, which could be useful for clinical and research
      purposes.

PMID- 29223184
TI  - Older marijuana users' marijuana risk perceptions: associations with marijuana
      use patterns and marijuana and other substance use disorders.
AB  - : ABSTRACTBackground:Compared to their non-using age peers, older marijuana users
      are known to have lower marijuana risk perceptions. We examined associations of
      older marijuana users' risk perceptions with their marijuana use patterns and
      substance use disorders. METHODS: Data are from 2013 to 2015 National Survey of
      Drug Use and Health (N = 24,057 respondents aged 50+ years). Bivariate logistic
      regression was used to compare risk perceptions among never users, former users,
      and past-year users aged 50+ years. Multivariable logistic regression was used to
      test associations between risk perception and marijuana use status and between
      risk perception and marijuana use patterns. RESULTS: Among the total sample,
      former (AOR = 0.30, 95% CI = 0.27-0.32) and past-year (AOR = 0.05, 95% CI = 0.04
      0.06) marijuana users had significantly lower odds of moderate/great risk
      perception (as opposed to no/slight risk perception) than never users. Among past
      year users, odds of moderate/great risk perception were lower among those who
      used marijuana more frequently (AOR = 0.14, 95% CI = 0.07-0.28 for 300+ days of
      use compared to 1-11 days of use) and who reported any medical marijuana use (AOR
      = 0.27, 95% CI = 0.14-0.51). However, those who had marijuana use disorder were
      3.5 times more likely to report moderate/great risk perception (AOR = 3.50, 95%
      CI = 1.62-7.58). Those who had a college education, had higher incomes, and
      resided in states with medical marijuana laws also had lower risk perceptions.
      CONCLUSIONS: Public health education on scientific evidence about marijuana's
      benefits and harms and age-appropriate treatment for older adults with substance
      use problems are needed. Research on risk perception formation using longitudinal
      data among older adults is also needed.

PMID- 29223185
TI  - Aiding medical professionals in fitness-to-drive screenings for elderly drivers:
      development of an office-based screening tool.
AB  - : ABSTRACTBackground:Elderly drivers are an increasing group in society. Previous
      research has found that functional and cognitive abilities are more important for
      driving abilities than biological age. In an attempt to conserve independent
      mobility for elderly drivers, many researchers have focused on elderly drivers
      diagnosed with cognitive decline (mild cognitive impairment or mild Dementia).
      This study is the first to focus on elderly drivers with cognitive complaints or
      suspected of diminished fitness to drive by an (in)formal caregiver as an at-risk
      group. METHODS: The main objective of this study was to develop a fitness to
      drive screening tool for elderly drivers to be used in a doctor's office.
      Furthermore, this study investigated the additional value of driving simulator
      tests in the assessment of fitness to drive. Both screenings (functional
      abilities and driving simulator test) were benchmarked against the official
      Belgian fitness to drive licensing procedure. RESULTS: One-hundred thirty-six
      elderly drivers participated in a functional abilities screening, a driving
      simulator assessment and an on-road driving test. Sixty-five percent of the
      sample was considered fit to drive. Visual acuity, physical flexibility, and
      knowledge of road signs were found to be the best predictive set of tests for the
      on-road fitness to drive outcome. A performance based driving simulator
      assessment increased predictive accuracy significantly. CONCLUSION: The proposed
      screening procedure saves part of the at-risk elderly driver population from
      stressful and costly on-road driving evaluations. This procedure provides more
      information of an individual driver's specific driving parameters. This opens
      doors for personalized older driver training to maintain independent mobility in
      later life.

PMID- 29223186
TI  - Willingness of Firefighting Program Students to Work in Disasters-Turkey.
AB  - : Introduction Firefighting is an important profession during disasters.
      Firefighters are on duty for many vital functions, including fire extinguishing,
      search and rescue work, and evacuation of disaster victims to a safe zone. In
      case of a disaster situation, it is vital to have willing personnel to work in
      disasters. In the literature, type of disaster, individual demographic factors,
      family factors, and workplace factors have been identified as factors that
      influence health care personnel's willingness to work during a disaster. However,
      little is known about firefighters and firefighter candidates' willingness to
      work in a disaster. Hypothesis/Problem This study was aimed to identify the
      willingness of civil defense and firefighting program students to work in
      different disasters after graduation and the factors associated with their
      willingness. METHODS: The universe of this descriptive, epidemiological study was
      1,116 students of civil defense and firefighting programs in Turkey. They were
      from 11 different universities. In the research study, a sample was not chosen as
      it was aimed at reaching the whole universe. A standardized survey form of 58
      questions, prepared by researchers, was used to gather data. RESULTS: The rate of
      participation was 65.5%. Of the students, 82.8% said that after graduation they
      would like to work in disasters, whereas 16.2% were indecisive. The students were
      less willing to work in nuclear accidents (42.4%) and epidemic disasters (32.1%).
      In chi-square analysis, "willingness of students to work in disasters after
      graduation" (dependent variable) and the independent variables: "university of
      student," "exercising regularly," "having a hobby related to disaster," "having
      been educated about disaster," and "being satisfied from the received education"
      were found statistically significant. When students' willingness to work in
      disasters after graduation (ref=unwilling) was analyzed with multi-variate
      analysis, only "university of students" and "having a hobby related to disasters"
      were found statistically significant. CONCLUSION: Overall, 16.2% of the students
      stated that they were indecisive to work in disasters in the future, and 1.0% of
      them stated that they did not want to work in disasters. Moreover, willingness of
      students to work in nuclear accident and contagious disease disasters has been
      found to be lower compared to other disaster types. Kaya E , Altintas H .
      Willingness of firefighting program students to work in disasters-Turkey. Prehosp
      Disaster Med. 2018;33(1):13-22.

PMID- 29223187
TI  - Children's comprehension of contrastive connectives.
AB  - Production studies show connective acquisition by age 3;0, but comprehension
      studies show errors until 9;0 or older. To further investigate this gap, two
      comprehension tasks were carried out with 78 Dutch children between the ages of
      7;0 and 10;1, testing contrastive maar 'but' and causal want 'because'
      connectives for comparison. An existing context choice task and a task that
      tested children's ability to interpret pronouns dependent on the connective were
      used. Children did well on the context choice task for want 'because', but
      performed far below chance with maar 'but'. In the pronoun interpretation task
      the youngest children performed at or near chance with both connectives, but show
      gradual improvement with age. Task complexity may partially explain the results
      but in general, they are consistent with previous experiments showing contrastive
      connective comprehension is acquired very late compared to their correct
      production. Further, the pronoun interpretation task may give a more accurate
      picture of understanding.

PMID- 29223189
TI  - The evaluation of arterial stiffness of essential hypertension and white coat
      hypertension in children: a case-control study.
AB  - BACKGROUND: The aim of this study was to determine and compare cardiovascular
      risks by assessing arterial stiffness in children with essential hypertension and
      white coat hypertension. METHODS: Paediatric patients followed up with essential
      hypertension and white coat hypertension diagnoses and with no established end
      organ damage were involved in the study. Arterial stiffness in children included
      in the study was evaluated and compared by using the oscillometric device (Mobil
      O-Graph) method. RESULTS: A total of 62 essential hypertension (34 male, 28
      female), 38 white coat hypertension (21 male, 17 female), and 60 healthy controls
      (33 male, 27 female) were assessed in the present study. Pulse wave velocity of
      the essential hypertension, white coat hypertension, and control group was,
      respectively, as follows: 5.3+/-0.6 (m/s), 5.1+/-0.4 (m/s), 4.3+/-0.4 (m/s)
      (p<0.001); augmentation index outcomes were, respectively, determined as follows:
      21.3+/-6.5, 19.3+/-6.4, 16.0+/-0.3 (p<0.001). Pulse wave velocity and
      augmentation index values of children with essential hypertension and white coat
      hypertension were found to be higher compared with the control group. This level
      was identified as correlated with the duration of hypertension in both patient
      groups (p<0.01). CONCLUSION: Arterial stiffness in children with essential
      hypertension and white coat hypertension was impaired compared with healthy
      children. This finding has made us think that white coat hypertension is not an
      innocent clinical situation. This information should be taken into consideration
      in the follow-up and treatment approaches of the patients.

PMID- 29223188
TI  - Disordered eating in Sami and non-Sami Norwegian populations: the SAMINOR 2
      Clinical Survey.
AB  - OBJECTIVE: The present study aimed to investigate disordered eating (DE) among
      Sami compared with non-Sami residing in northern Norway. DESIGN: In a cross
      sectional design, stratified by sex and ethnicity, associations were tested
      between DE (Eating Disturbance Scale; EDS-5) and age, education level, BMI
      category, anxiety and depression, physical activity and consumption of snacks.
      SETTING: The SAMINOR 2 Clinical Survey (2012-2014) based on the population of ten
      municipalities in northern Norway. SUBJECTS: Adults aged 40-69 years; 1811 Sami
      (844 male, 967 female) compared with 2578 non-Sami (1180 male, 1398 female)
      individuals. RESULTS: No overall significant ethnic difference in DE was
      identified, although comfort eating was reported more often by Sami individuals
      (P=0.01). Regardless of ethnicity and sex, symptoms of anxiety and depression
      were associated with DE (P<0.001). Furthermore, DE was more common at lower age
      and higher BMI values. Education levels were protectively associated with DE
      among Sami men (P=0.01). DE was associated (OR, 95% CI) with low physical
      activity in men in general and in non-Sami women (Sami men: 2.4, 1.4, 4.0; non
      Sami men: 2.2, 1.4, 3.6; non-Sami women: 1.8, 1.2, 2.9) and so was the
      consumption of snacks (Sami men: 2.6, 1.3, 5.0; non-Sami men: 1.9, 1.1, 3.1; non
      Sami women: 2.1, 1.3, 3.4). CONCLUSIONS: There were no significant differences
      regarding overall DE comparing Sami with non-Sami, although Sami more often
      reported comfort eating. There were significant sex and ethnic differences
      related to DE and physical activity, snacking and education level.

PMID- 29223190
TI  - Educational effects on ascertain dementia 8-item informant questionnaire to
      detect dementia in the Taiwanese population.
AB  - : ABSTRACTBackground:Dementia screening is a public health priority in Taiwan,
      where the prevalence of dementia is increasing because of an aging population.
      However, the reasons affect community-dwelling people to accept a referral to
      memory specialist clinic after dementia screening was still unclear. To
      investigate the feasibility, acceptability, sensitivity, and specificity of the
      ascertain dementia 8-item informant questionnaire (AD8) to screen for patients
      with cognitive impairments in Taiwan's primary healthcare system. METHODS:
      Researchers invited community-dwelling people whose age was above 50-year-old to
      attend the Memory Screening Project. AD8 was used to perform the informant
      interview with adult patients who were attending the Memory Screening Project in
      Taiwan. Individuals who scored >=2 on the AD8 was suggested to accept referral
      for further cognitive performance evaluation tests, which included three
      validated dementia tests, i.e. the Mini-Mental Screening Examination (MMSE), the
      Cognitive Abilities Screening Instrument (CASI), and the Clinical Dementia Rating
      (CDR). RESULTS: Of the 102 participants who scored >=2 on the AD8, only 25.5%
      attended the referral appointment. In participants who had achieved six or more
      years of education, AD8 scores were not significantly different between groups
      and could not differentiate between the non-dementia and patients with dementia
      in the receiver-operator characteristics curve analysis. In contrast, in those
      participants who had received less than six years of education, the AD8 scores
      significantly differentiated between non-dementia and patients with dementia (p =
      0.03). CONCLUSIONS: There was a low rate of attendance at a specialist memory
      clinic following referral after the AD8 interview. Higher levels of education
      facilitated individuals to make a decision to accept the recommended referral
      appointment, while the AD8 showed a higher rate of differentiation between
      individuals who had received an education of less than six years.

PMID- 29223191
TI  - Iterating a framework for the prevention of caregiver depression in dementia: a
      multi-method approach.
AB  - : ABSTRACTBackground:Dementia caregiving is often stressful and depression in
      family caregivers is not uncommon. As caregiver depression can have significant
      effects, there is a need for preventive efforts which are consistent with the
      extensive literature. We sought to consolidate the wide range of evidence (using
      a multi-method approach) into a simple framework that can guide the prevention of
      caregiver depression. METHODS: Using multiple logistic regression, we derived the
      predictors of caregiver depression from an empirical dataset containing key
      information and depression scores (based on the Center-for-Epidemiological
      Studies-Depression-Scale) of 394 family caregivers. We then chose an underpinning
      theory as the foundation of the framework, and conducted an umbrella systematic
      review to find possible links between the derived predictors and the theory.
      Last, we compared the iterated framework with known interventions for caregiver
      depression in recent literature to assess whether the framework could map
      meaningfully with the known interventions. RESULTS: Significant predictors of
      caregiver depression included primary caregiver (odds ratio, OR = 1.53), severe
      dementia (OR = 1.40), and behavioral problems (OR = 3.23), lower education (OR =
      1.77), and spousal caregivers (OR = 1.98). The integrated framework derived
      focuses on four strategic areas: physical-care demands of persons with dementia
      (PWD), behavioral problems of PWD, caregiving competency, and loss and grief of
      caregivers. This framework is supported by known interventions for caregiver
      depression in recent literature. CONCLUSIONS: By consolidating a broad range of
      evidence, we iterated a framework to aid the understanding and prevention of
      caregiver depression in dementia. The framework offers an approach to prevention
      which is simple, systematic, and reflective of the extensive literature.

PMID- 29223192
TI  - Training needs for dementia care in China from the perspectives of mental health
      providers: who, what, and how.
AB  - : ABSTRACTBackground:Acknowledging increasing demand of dementia care for
      patients in China, this paper aims to understand the training needs of dementia
      care from the perspectives of mental health providers by examining who should be
      the trainees, what should be the contents of training, and how to deliver the
      training in China. METHODS: Using purposive sampling, data were gathered via four
      focus group discussions with 40 mental health providers in Beijing, China, in
      2011. Data were transcribed by independent investigators and then translated into
      English. Researchers used content analysis to separately identify themes and
      codes. Discrepancies were discussed until final agreement achieved. RESULTS: To
      improve the quality of dementia care, all participants agreed there is a
      significant need to train both formal or professional (physicians, nurses,
      hospital administrators, community workers) and informal caregivers (family,
      friends, or non-kin hired caregivers). For formal or professional caregivers,
      suggested training content included clinical knowledge of dementia (i.e.
      pathogenesis, approaches for preventing dementia deterioration) and clinical
      practice skills (i.e. diagnostic, treatment, caregiving, counseling,
      communicating skills). For informal caregivers, basic dementia knowledge and home
      based caregiving skills such as safety, restorative, stress management, and
      communication were identified as key training contents. Multilevel support from
      the government and community centers were considered crucial factors to
      delivering the training and educating the public to enhance awareness of
      dementia. CONCLUSIONS: Culturally, sensitive education and specific trainings for
      formal and informal dementia caregivers are urgently needed in China. Policy and
      program implications are discussed.

PMID- 29223193
TI  - Quality Indicators for Evaluating Prehospital Emergency Care: A Scoping Review.
AB  - : Introduction Historically, the quality and performance of prehospital emergency
      care (PEC) has been assessed largely based on surrogate, non-clinical endpoints
      such as response time intervals or other crude measures of care (eg, stakeholder
      satisfaction). However, advances in Emergency Medical Services (EMS) systems and
      services world-wide have seen their scope and reach continue to expand. This has
      dictated that novel measures of performance be implemented to compliment this
      growth. Significant progress has been made in this area, largely in the form of
      the development of evidence-informed quality indicators (QIs) of PEC. Problem
      Quality indicators represent an increasingly popular component of health care
      quality and performance measurement. However, little is known about the
      development of QIs in the PEC environment. The purpose of this study was to
      assess the development and characteristics of PEC-specific QIs in the literature.
      METHODS: A scoping review was conducted through a search of PubMed (National
      Center for Biotechnology Information, National Institutes of Health; Bethesda,
      Maryland USA); EMBase (Elsevier; Amsterdam, Netherlands); CINAHL (EBSCO
      Information Services; Ipswich, Massachusetts USA); Web of Science (Thomson
      Reuters; New York, New York USA); and the Cochrane Library (The Cochrane
      Collaboration; Oxford, United Kingdom). To increase the sensitivity of the
      literature, a search of the grey literature and review of select websites was
      additionally conducted. Articles were selected that proposed at least one PEC QI
      and whose aim was to discuss, analyze, or promote quality measurement in the PEC
      environment. RESULTS: The majority of research (n=25 articles) was published
      within the last decade (68.0%) and largely originated within the USA (68.0%).
      Delphi and observational methodologies were the most commonly employed for QI
      development (28.0%). A total of 331 QIs were identified via the article review,
      with an additional 15 QIs identified via the website review. Of all, 42.8% were
      categorized as primarily Clinical, with Out-of-Hospital Cardiac Arrest
      contributing the highest number within this domain (30.4%). Of the QIs
      categorized as Non-Clinical (57.2%), Time-Based Intervals contributed the
      greatest number (28.8%). Population on Whom the Data Collection was Constructed
      made up the most commonly reported QI component (79.8%), followed by a
      Descriptive Statement (63.6%). Least reported were Timing of Data Collection
      (12.1%) and Timing of Reporting (12.1%). Pilot testing of the QIs was reported on
      34.7% of QIs identified in the review. CONCLUSION: Overall, there is considerable
      interest in the understanding and development of PEC quality measurement.
      However, closer attention to the details and reporting of QIs is required for
      research of this type to be more easily extrapolated and generalized. Howard I ,
      Cameron P , Wallis L , Castren M , Lindstrom V . Quality indicators for
      evaluating prehospital emergency care: a scoping review. Prehosp Disaster Med.
      2018;33(1):43-52.

PMID- 29223194
TI  - Hospital-Confirmed Acute Myocardial Infarction: Prehospital Identification Using
      the Medical Priority Dispatch System.
AB  - : Introduction Early recognition of an acute myocardial infarction (AMI) can
      increase the patient's likelihood of survival. As the first point of contact for
      patients accessing medical care through emergency services, emergency medical
      dispatchers (EMDs) represent the earliest potential identification point for
      AMIs. The objective of the study was to determine how AMI cases were coded and
      prioritized at the dispatch point, and also to describe the distribution of these
      cases by patient age and gender. Hypothesis/Problem No studies currently exist
      that describe the EMD's ability to correctly triage AMIs into Advanced Life
      Support (ALS) response tiers. METHODS: The retrospective descriptive study
      utilized data from three sources: emergency medical dispatch, Emergency Medical
      Services (EMS), and emergency departments (EDs)/hospitals. The primary outcome
      measure was the distributions of AMI cases, as categorized by Chief Complaint
      Protocol, dispatch priority code and level, and patient age and gender. The EMS
      and ED/hospital data came from the Utah Department of Health (UDoH), Salt Lake
      City, Utah. Dispatch data came from two emergency communication centers covering
      the entirety of Salt Lake City and Salt Lake County, Utah. RESULTS: Overall,
      89.9% of all the AMIs (n=606) were coded in one of the three highest dispatch
      priority levels, all of which call for ALS response (called CHARLIE, DELTA, and
      ECHO in the studied system). The percentage of AMIs significantly increased for
      patients aged 35 years and older, and varied significantly by gender, dispatch
      level, and chief complaint. A total of 85.7% of all deaths occurred among
      patients aged 55 years and older, and 88.9% of the deaths were handled in the ALS
      recommended priority levels. CONCLUSION: Acute myocardial infarctions may present
      as a variety of clinical symptoms, and the study findings demonstrated that more
      than one-half were identified as having chief complaints of Chest Pain or
      Breathing Problems at the dispatch point, followed by Sick Person and
      Unconscious/Fainting. The 35-year age cutoff for assignment to higher priority
      levels is strongly supported. The Falls and Sick Person Protocols offer
      opportunities to capture atypical AMI presentations. Clawson JJ , Gardett I ,
      Scott G , Fivaz C , Barron T , Broadbent M , Olola C . Hospital-confirmed acute
      myocardial infarction: prehospital identification using the Medical Priority
      Dispatch System. Prehosp Disaster Med. 2018;33(1):29-35.

PMID- 29223195
TI  - Advanced Modeling Methods for Studying Individual Differences and Dynamics in
      Organizations: Introduction to the Special Issue.

PMID- 29223196
TI  - Application of Psychological Theories in Agent-Based Modeling: The Case of the
      Theory of Planned Behavior.
AB  - It is likely that computer simulations will assume a greater role in the next
      future to investigate and understand reality (Rand & Rust, 2011). Particularly,
      agent-based models (ABMs) represent a method of investigation of social phenomena
      that blend the knowledge of social sciences with the advantages of virtual
      simulations. Within this context, the development of algorithms able to recreate
      the reasoning engine of autonomous virtual agents represents one of the most
      fragile aspects and it is indeed crucial to establish such models on well
      supported psychological theoretical frameworks. For this reason, the present work
      discusses the application case of the theory of planned behavior (TPB; Ajzen,
      1991) in the context of agent-based modeling: It is argued that this framework
      might be helpful more than others to develop a valid representation of human
      behavior in computer simulations. Accordingly, the current contribution considers
      issues related with the application of the model proposed by the TPB inside
      computer simulations and suggests potential solutions with the hope to contribute
      to shorten the distance between the fields of psychology and computer science.

PMID- 29223197
TI  - An Estimation of a Nonlinear Dynamic Process Using Latent Class Extended Mixed
      Models: Affect Profiles After Terrorist Attacks.
AB  - Conceptualizing affect as a complex nonlinear dynamic process, we used latent
      class extended mixed models (LCMM) to understand whether there were unobserved
      groupings in a dataset including longitudinal measures. Our aim was to identify
      affect profiles over time in people vicariously exposed to terrorism, studying
      their relations with personality traits. The participants were 193 university
      students who completed online measures of affect during the seven days following
      two terrorist attacks (Paris, November 13, 2015; Brussels, March 22, 2016); Big
      Five personality traits; and antecedents of affect. After selecting students
      whose negative affect was influenced by the two attacks (33%), we analysed the
      data with the LCMM package of R. We identified two affect profiles, characterized
      by different trends over time: The first profile comprised students with lower
      positive affect and higher negative affect compared to the second profile.
      Concerning personality traits, conscientious-ness was lower for the first profile
      compared to the second profile, and vice versa for neuroticism. Findings are
      discussed for both their theoretical and applied relevance.

PMID- 29223198
TI  - Second-Order Growth Mixture Modeling in Organizational Psychology: An Application
      in the Study of Job Performance Using the Cusp Catastrophe Model.
AB  - In recent years, research in organizational psychology has witnessed a shift in
      attention from a mostly variable-focused approach, to a mostly person-focused
      approach. Indeed, it has been widely recognized that the study of worker's
      heterogeneity is a meaningful and necessary task of researchers dealing with
      human behavior in organizational contexts. As a consequence, there has been
      growing interest in the application of statistical analyses able to uncover
      latent sub-groups of workers. The present contribution was conceived as a
      tutorial for the application of one of these statistical analyses, namely second
      order growth mixture modeling, and to illustrate its inner links with concepts
      from non-linear dynamic models. Throughout the paper, we provided (a) a
      discussion on the relationships between growth mixture modeling and the cusp
      catastrophe model; (b) Mplus syntaxes and output excerpts of a longitudinal
      analysis conducted on job performance (N = 420 employees rated once a year for
      four consecutive years);

PMID- 29223199
TI  - The Influence of Homophilous Interactions on Diversity Effects in Group Problem
      Solving.
AB  - Increasingly diversity researchers call for further studies of group micro
      processes and dynamics to understand the paradoxical effects of diversity on
      group performance. In this study, based on analyses of in-group, networked,
      homophilous interactions, we aim to explain further the effects of diversity on
      group performance in a parallel problem-solving task, both experimentally and
      computationally. We developed a 'whodunit' problem-solving experiment with 116
      participants assigned to different-sized groups. Experimental results show that
      low diversity and high homophily levels are associated with lower performance
      while the effects of group size are not significant. To investigate this further,
      we developed an agent-based computational model (ABM), through which we inspected
      (a) the effect of different homophily and diversity strengths on performance, and
      (b) the robustness of such effects across group size variations. Overall,
      modeling results were consistent with our experimental findings, and revealed
      that the strength of homophily can drive diversity towards a positive or negative
      impact on performance. We also observed that increasing group size has a very
      marginal effect. Our work contributes to a better understanding of the
      implications of diversity in-group problem-solving by providing an integration of
      both experimental and computational perspectives in the analysis of group
      processes.

PMID- 29223200
TI  - Emotions as Proximal Causes of Word of Mouth: A Nonlinear Approach.
AB  - Service research tends to operationalize word of mouth (WOM) behavior as one of
      the many responses to service satisfaction. In this sense, little is known about
      its antecedents or moderators. The objective of this study was to investigate the
      role of customers' emotions during service experiences on WOM, applying nonlinear
      techniques and exploring the moderating role of customers' propensity for
      emotional contagion. Using the critical incidents technique, 122 customers
      recalled significant service experiences and the emotions they aroused, and
      reported if they shared said experiences with other individuals. We found that,
      whereas linear methods presented non-significant results in the emotions-WOM
      relationship, nonlinear ones (artificial neural networks) explained 46% of
      variance. Negative emotions were stronger predictors of WOM and the importance of
      emotions for WOM was significantly higher for individuals with high propensity
      for emotional contagion (R^2 = .79) than for those with lower levels (R^2 = .48).
      Theoretical and practical implications are discussed.

PMID- 29223201
TI  - Investigating Balance in Teacher Job Attitudes using Polynomial Regression and
      Response Surface Methodology.
AB  - Organizational theorists have long advocated the importance of attending to
      multiple stakeholders. However, limited empirical research has been devoted to
      the ways in which to identify balance, or imbalance, between stakeholder groups
      possibly due to methodological issues with modeling such complex nomological
      nets. The current study utilized the multiple stakeholder climate framework to
      test hypothesized relationships between perceptions of support and affectively
      based criteria using polynomial regression and response surface methodology to
      test discreet regression lines representing predictions. Results from 297
      teachers surveyed indicated that support for each group led to positive outcomes
      for teachers (higher job-specific positive affect and organiza-tional commitment,
      and lower negative affect). Further, when the support for teachers exceeded or
      fell short of the support for students, indicating imbalance, negative affect
      increased.

PMID- 29223202
TI  - Evidence of Chaos in a Routine Watchstanding Task.
AB  - Research into human performance on naval ships often emphasizes the significance
      of shaping factors, such as vigilance, fatigue and circadian rhythm. However, few
      report on the presence of complex nonlinear dynamics and fractal dimensionality.
      This study examines over 7000 routine topside security checks on a U.S. Navy
      Destroyer performed over a twelve-month period. Time series analysis (0-1 test,
      analysis of Lyapunov exponent, state space plots, and graphical analysis) reveal
      the presence of chaotic behavior, harmonics attractors, and fractal structures.
      The presence of this level of complexity in a simple task demonstrates the need
      to integrate previous findings in human performance with new discoveries in
      complexity and fractional dynamics.

PMID- 29223204
TI  - Civil Discourse and Peer Review.

PMID- 29223203
TI  - [Editorial].

PMID- 29223205
TI  - Dietary Approach to Reflux.

PMID- 29223206
TI  - A Call to Action to Address Barriers to Breastfeeding and Lactation Faced by
      Student-Mothers.
AB  - Many new mothers returning to school after childbirth face barriers within their
      academic settings to meeting their goals for exclusive breastfeeding. Potential
      barriers to breastfeeding faced by student-mothers include lack of legal
      protection, lack of breastfeeding-friendly university policies, inadequate
      availability of breastfeeding facilities, and insufficient awareness of the
      importance of breastfeeding among mothers, health care providers, and university
      administrators and faculty. Here we advocate for six action steps to help remove
      barriers to breastfeeding faced by student-mothers.

PMID- 29223207
TI  - Commentary on a Cochrane Review of Screening for Intimate Partner Violence in
      Health Care Settings.
AB  - Intimate partner violence is a universal phenomenon that warrants awareness by
      all health care providers. This article summarizes a Cochrane Review on screening
      women for intimate partner violence in health care settings. The review authors
      identified 13 randomized controlled trials and quasi-randomized controlled trials
      that assessed the effectiveness of screening for intimate partner violence. The
      authors concluded that there was insufficient evidence to justify implementation
      of universal screening for intimate partner violence.

PMID- 29223208
TI  - Implementing Evidence-Based Neonatal Skin Care With Parent-Performed, Delayed
      Immersion Baths.
AB  - There has been a recent trend toward delaying newborn baths because of mounting
      evidence that delayed bathing promotes breastfeeding, decreases hypothermia, and
      allows for more parental involvement with newborn care. A multidisciplinary team
      from a maternal-new-born unit at a military medical center designed and
      implemented an evidence-based practice change from infant sponge baths shortly
      after birth to delayed immersion baths. An analysis of newborn temperature data
      showed that newborns who received delayed immersion baths were less likely to be
      hypothermic than those who received a sponge bath shortly after birth.
      Furthermore, parents reported that they liked participating in bathing their
      newborns and that they felt prepared to bathe them at home.

PMID- 29223209
TI  - Nurse-Led Initiatives to Implement Universal Screening for Perinatal Emotional
      Complications.
AB  - Perinatal emotional complications are the most common pregnancy complications in
      the United States. This article reviews three recent studies that illustrate the
      prevalence of and risk factors for perinatal emotional complications and sheds
      light on the inconsistency of screening by health care providers in acute care
      and outpatient settings. Also presented is an example of nurse-led quality
      improvement initiatives aimed at implementing universal screening in a rural New
      England county, which resulted in 100% screening with the Edinburgh Postnatal
      Depression Scale across health care facilities within the community, as well as a
      system-wide change in the approach to identifying and treating perinatal
      emotional complications.

PMID- 29223210
TI  - Providing Evidence-Based Care During the Golden Hour.
AB  - The Golden Hour encompasses a set of evidence-based practices that contribute to
      the physiologic stabilization of the mother-newborn dyad after birth. Important
      elements of the Golden Hour include delayed cord clamping, skin-to-skin contact
      for at least an hour, the performance of newborn assessments on the maternal
      abdomen, delaying non-urgent tasks (e.g., bathing the newborn) for 60 minutes,
      and the early initiation of breastfeeding. The Golden Hour contributes to
      neonatal thermoregulation, decreased stress levels in a woman and her newborn,
      and improved mother-newborn bonding. Implementation of these actions is further
      associated with increased rates and duration of breastfeeding. This article
      explores the evidence supporting the Golden Hour and provides strategies for
      successfully implementing a Golden Hour protocol on a hospital-based labor and
      delivery unit.

PMID- 29223211
TI  - Perinatal and Neonatal Implications of Sickle Cell Disease.
AB  - Sickle cell disease is the genetic disorder most commonly detected with state
      mandated newborn screening. Women with sickle cell disease struggle with
      psychosocial, emotional, and physical challenges throughout their lives.
      Pregnancy for women with sickle cell disease brings greater risk for maternal and
      fetal morbidity and mortality and increased likelihood of hospitalization for
      complications, including sickle cell pain crisis. Chronic maternal opioid use for
      pain can place newborns at risk for neonatal abstinence syndrome. Care of a
      pregnant woman with sickle cell disease requires a collaborative,
      multidisciplinary team addressing the medical, social, and emotional needs of the
      woman and her family.

PMID- 29223212
TI  - How to Engage Your Team to Implement Delayed Cord Clamping.
AB  - This article describes how a health care team changed practice by implementing
      delayed cord clamping as standard practice. After administration of a survey to
      assess clinicians' knowledge and to discover barriers to this proposed practice
      change, members of a multidisciplinary committee used the results to create a
      guideline for delayed cord clamping and a plan for successful implementation.
      Integral to embedding and sustaining changes in practice was development of the
      Delivery Room Brief and Debrief Tool and inclusion of the process into nursing
      guidelines and the electronic health record. Through the use of these tools and
      teamwork, delayed cord clamping was implemented as standardized practice across
      six hospitals within this health care system.

PMID- 29223215
TI  - Confidentiality in Adolescent Health Care.

PMID- 29223214
TI  - Emergency Contraception.

PMID- 29223213
TI  - Immigration Basics for Nurses.
AB  - The United States is known as a nation of immigrants and a land of promise that
      welcomes the needy, poor, and oppressed. Immigrants represent some of the most
      vulnerable in society. It is vital that nurses and other health care providers
      possess knowledge of social, economic, and political factors related to health
      care for immigrant populations. This article provides definitions of the various
      immigrant populations, addresses health needs within this group, and offers
      suggestions for nursing practice and advocacy.

PMID- 29223216
TI  - Proud and Grateful to Be a Nurse and an Educator.

PMID- 29223217
TI  - Editorial overview.

PMID- 29223218
TI  - [New paradigms for endometrial cancers treatment!]

PMID- 29223219
TI  - The Intergenerational Impact of Prenatal Stress: Time to Focus on Prevention?

PMID- 29223220
TI  - Relevance of Psychological Symptoms in Pregnancy to Intergenerational Effects of
      Preconception Trauma.

PMID- 29223221
TI  - Gut Microbes and Brain Development Have Black Box Connectivity.

PMID- 29223222
TI  - From "Azalla" to Anandamide: Distilling the Therapeutic Potential of
      Cannabinoids.

PMID- 29223223
TI  - Cataract surgery in patients with diabetes.

PMID- 29223224
TI  - Combined interface tattooing and fibrin glue-assisted sutureless corneal
      resurfacing with donor lenticule obtained from small-incision lenticule
      extraction for limbal dermoid.
AB  - We describe a technique of small-incision lenticule extraction (SMILE)-assisted
      sutureless corneal resurfacing with interface tattooing for superficial limbal
      dermoids. After excision at a plane minimally below surrounding normal cornea and
      sclera, a corneal tattoo powder is carefully applied within an inked circular
      outline of the intended corneal margin. Circularity and cosmesis are assessed in
      natural light with the microscope light off. Fibrin glue-assisted corneal
      resurfacing is performed with the lenticule. The conjunctiva is closed with glue.
      The technique was performed in 3 patients, who had satisfactory cosmetic and
      refractive effects and decreased corneal astigmatism (follow-up 12 to 25 months).
      The technique is safe, effective, and fast with good cosmetic and refractive
      effects. It retains tectonic stability and decreases the risk for complications
      such as intraoperative perforation, postoperative limbal ectasia, and visible
      corneal scarring. A similar technique with a microkeratome-created thin flap on a
      donor cornea was alternatively performed by us in the absence of donor
      lenticules.

PMID- 29223225
TI  - Poor glycemic control as a risk factor for pseudophakic cystoid macular edema in
      patients with diabetes.
AB  - PURPOSE: To specify the risk factors for pseudophakic cystoid macular edema (CME)
      in patients with diabetes. SETTING: Kymenlaakso Central Hospital, Unit of
      Ophthalmology, Kotka, Finland. DESIGN: Prospective case series. METHODS: Patients
      with type 1 or type 2 diabetes having routine cataract surgery were evaluated.
      Spectral-domain optical coherence tomography imaging was performed before surgery
      and 1 month postoperatively. RESULTS: The study comprised 93 patients (95 eyes).
      The central retinal thickness increase was 9.7 MUm +/- 1.7 (SEM) in diabetic
      patients with no retinopathy, 22.7 +/- 8.6 MUm in those who had nonproliferative
      retinopathy, and 73.8 +/- 37.4 MUm in those who had proliferative retinopathy (P
      < .001). The central retinal thickness increase was greater in the eyes of
      diabetic patients with insulin dependence than in eyes of patients using
      noninsulin medication (21.9 +/- 5.9 MUm versus 8.3 +/- 1.8 MUm, P = .017). Serum
      hemoglobin A1c concentration and inversely, patient age, were associated with
      central retinal thickness increase, even after adjustment for confounding factors
      (r = 0.607, P < .001 and r = 0.417, P = .001, respectively). The central retinal
      thickness change was smaller in the eyes of patients who had a nonsteroidal
      antiinflammatory drug (NSAID) as their postoperative antiinflammatory medication
      than in eyes of patients who were not prescribed NSAID medication when
      retinopathy was analyzed as a covariant (8.2 +/- 3.6 MUm versus 13.6 +/- 2.9 MUm,
      P = .016). CONCLUSIONS: Young patient age and poor glycemic control were risk
      factors for postoperative central retinal thickness increase. This study showed
      it is necessary to identify, effectively treat, and follow-up with patients with
      diabetes who are at a greater risk for pseudophakic CME.

PMID- 29223226
TI  - Clinical implication of triamcinolone in aqueous humor after depository sub-Tenon
      application.
AB  - PURPOSE: To determine the triamcinolone concentration in the aqueous humor after
      anterior sub-Tenon injection versus posterior sub-Tenon injection and the
      possible association between the levels of triamcinolone in the aqueous and the
      elevation in intraocular pressure (IOP). SETTING: University teaching hospitals
      at Wenzhou and Shanghai, China. DESIGN: Prospective case series. METHODS: The
      aqueous humor was sampled and triamcinolone quantitated after anterior sub-Tenon
      injection or posterior sub-Tenon injection in a cohort of patients and in
      experimental rabbits. Patients' IOPs were measured before and up to 3 months
      after triamcinolone acetonide injection. RESULTS: The study comprised 46 patients
      and 18 rabbits. The mean aqueous humor triamcinolone concentration in rabbit eyes
      and human eyes was significantly higher after an anterior sub-Tenon injection
      than that after a posterior sub-Tenon injection (rabbit eye: anterior sub-Tenon
      injection, 2.67 ng/mL +/- 0.78 [SD] and posterior sub-Tenon injection 1.38 +/-
      0.48 ng/mL; human eye: 133.8 +/- 149.2 ng/mL and 10.2 +/- 10.9 ng/mL,
      respectively) (both P < .0001). After anterior sub-Tenon injection, the mean
      triamcinolone concentration in the aqueous humor was significantly higher in
      human eyes than in rabbit eyes (133.8 +/- 149.2 ng/mL versus 11.0 +/- 8.1 ng/mL)
      (P = .0003). The levels of triamcinolone in the human aqueous humor had a
      significant positive association with the elevation in IOP (beta = 0.12, P =
      .026). CONCLUSIONS: The triamcinolone level in aqueous humor was associated with
      IOP elevation after sub-Tenon application. Posterior sub-Tenon injection with a
      small injection volume of concentrated suspension offered a better targeted
      delivery and might significantly reduce steroid-associated IOP elevation.

PMID- 29223227
TI  - Cataract surgery and environmental sustainability: Waste and lifecycle assessment
      of phacoemulsification at a private healthcare facility.
AB  - PURPOSE: To measure the waste generation and lifecycle environmental emissions
      from cataract surgery via phacoemulsification in a recognized resource-efficient
      setting. SETTING: Two tertiary care centers of the Aravind Eye Care System in
      southern India. DESIGN: Observational case series. METHODS: Manual waste audits,
      purchasing data, and interviews with Aravind staff were used in a hybrid
      environmental lifecycle assessment framework to quantify the environmental
      emissions associated with cataract surgery. Kilograms of solid waste generated
      and midpoint emissions in a variety of impact categories (eg, kilograms of carbon
      dioxide equivalents). RESULTS: Aravind generates 250 grams of waste per
      phacoemulsification and nearly 6 kilograms of carbon dioxide-equivalents in
      greenhouse gases. This is approximately 5% of the United Kingdom's phaco carbon
      footprint with comparable outcomes. A majority of Aravind's lifecycle
      environmental emissions occur in the sterilization process of reusable
      instruments because their surgical system uses largely reusable instruments and
      materials. Electricity use in the operating room and the Central Sterile Services
      Department (CSSD) accounts for 10% to 25% of most environmental emissions.
      CONCLUSIONS: Surgical systems in most developed countries and, in particular
      their use of materials, are unsustainable. Results show that ophthalmologists and
      other medical specialists can reduce material use and emissions in medical
      procedures using the system described here.

PMID- 29223228
TI  - Endophthalmitis after cataract surgery: Effect of behind-the-lens washout.
AB  - PURPOSE: To analyze the outcomes of cataract surgery with emphasis on the
      relationship between surgery-related factors and the incidence of postoperative
      infectious endophthalmitis. SETTING: Ninety-three surgical sites in Japan.
      DESIGN: Prospective case series. METHODS: Eyes that were scheduled to have
      cataract surgery from January 20 to September 30, 2014, were included.
      Phacoemulsification and implantation of a single-piece hydrophobic acrylic
      foldable intraocular lens (IOL) were performed. Patients were followed for 2
      months. RESULTS: Of the 9720 eyes enrolled, 9100 (93.6%) completed a 2-month
      follow-up. Three cases (0.033%) developed infectious endophthalmitis (95%
      confidence interval [CI], 0.000-0.070). The incidence of endophthalmitis was
      significantly associated with the removal method of ophthalmic viscosurgical
      devices (OVDs) after IOL implantation. The incidences of endophthalmitis in cases
      with and without the behind-the-lens technique were 0% (0/6147; 95% CI, 0%) and
      0.084% (3/3570; 95% CI, 0.000-0.179), respectively, with a significant difference
      between them (P = .050, Fisher exact test). The incidence of infectious
      endophthalmitis did not correlate with any other patient-related and surgery
      related factors. CONCLUSION: The behind-the-lens technique to wash and clear the
      capsular bag for OVD removal significantly reduced the incidence of infectious
      endophthalmitis.

PMID- 29223229
TI  - Comparison of a new Scheimpflug imaging combined with partial coherence
      interferometry biometer and a low-coherence reflectometry biometer.
AB  - PURPOSE: To evaluate the repeatability of a new biometer using Scheimpflug
      technology combined with partial coherence interferometry (PCI) (Pentacam AXL)
      and its agreement with a device based on optical low-coherence reflectometry
      (OLCR), the Allegro Biograph. SETTING: Oftalvist Centro Integral Ocular Jerez,
      Jerez de la Frontera, Spain. DESIGN: Evaluation of a diagnostic test. METHODS:
      The mean keratometry (K), central corneal thickness (CCT), anterior chamber depth
      (ACD), and axial length (AL) were measured with the 2 devices 3 times by the same
      examiner in 2 groups (patients with cataract and patients without cataract). The
      repeatability was determined using the within-subject standard deviation, test
      retest repeatability, coefficient of variation, and intraclass correlation
      coefficient. The correlation was evaluated with the Pearson coefficient and
      interchangeability with the Bland-Altman plot. RESULTS: Eighty eyes (40 eyes in
      each group) of 80 patients were analyzed. Significant differences were found
      between the Scheimpflug-PCI device and the OLCR device for mean K in the normal
      group (P < .001) and for CCT in the normal group (P < .05) and the cataract group
      (P < .001). There were no differences between devices in ACD and AL in either
      group. The repeatability between devices was similar. Although a significant
      correlation between devices was found for all measurements (all P < .001), wide
      limits of agreement were found in both groups for all biometric parameters.
      CONCLUSIONS: The Scheimpflug-PCI and OLCR devices showed excellent intravisit
      repeatability and high correlation for mean K, CCT, ACD, and AL in healthy and
      cataractous eyes. No differences were found in AL; however, the 2 devices might
      not be interchangeable.

PMID- 29223230
TI  - Depth of focus after implantation of spherical or aspheric intraocular lenses in
      hyperopic and emmetropic patients.
AB  - PURPOSE: To evaluate whether hyperopic patients with short axial length and high
      dioptric intraocular lens (IOL) power can achieve a higher depth of focus after
      implantation of a monofocal spherical or aspheric IOL than emmetropic patients.
      SETTING: Department of Ophthalmology, Medical University Graz, Graz, Austria.
      DESIGN: Prospective case series. METHODS: Patients presenting for cataract
      surgery were divided by calculated IOL power into a hyperopic (>=22.0 diopters
      [D]) or emmetropic (18.0 to 21.5 D) groups and received an aspheric (Tecnis
      ZA9003) or a spherical IOL (Sensar AR40e). Postoperative measurements included
      corrected (CDVA) and uncorrected (UDVA) distance visual acuities, distance
      corrected intermediate (DCIVA) and near (DCNVA) visual acuities, root-mean-square
      values of corneal and total eye higher-order aberrations and spherical
      aberrations, and photopic and mesopic contrast sensitivity. RESULTS: Sixty-two
      eyes of 62 patients were enrolled in this study, 34 eyes (15 hyperopic, 19
      emmetropic) in the aspheric IOL group and 28 eyes (14 hyperopic, 14 emmetropic)
      in the spherical IOL group. The UDVA, CDVA, and contrast sensitivity did not
      differ significantly between the 2 IOL groups, whereas the DCIVA and DCNVA were
      significantly better in the spherical IOL group (P = .004 and P = .001,
      respectively). No significant differences were found in DCIVA and DCNVA between
      hyperopic patients and emmetropic patients with aspheric or spherical IOLs.
      CONCLUSIONS: Implantation of a monofocal spherical IOL resulted in an increased
      depth of focus without significant degradation of distance visual acuity or
      contrast sensitivity. There were no differences in the depth of focus between
      hyperopic eyes and emmetropic eyes.

PMID- 29223231
TI  - Pupil influence on the quality of vision in rotationally asymmetric multifocal
      IOLs with surface-embedded near segment.
AB  - PURPOSE: To evaluate the influences of preoperative pupil parameters on the
      visual outcomes of the SBL-3, a rotationally asymmetric multifocal intraocular
      lens (IOL) with a surface-embedded near segment. SETTING: Cathedral Eye Clinic,
      Belfast, Northern Ireland, United Kingdom. DESIGN: Retrospective comparative case
      series. METHODS: Postoperatively, patients divided into 4 groups according to
      their pupil size as follows: Group A: 2.50 to 2.99 mm, Group B: 3.00 to 3.50 mm,
      Group C: 3.51 to 4.00 mm, and Group D: 4.01 to 4.50 mm. The uncorrected distance
      (UDVA), intermediate (UIVA), and near (UNVA) visual acuities, IOL centration and
      tilt, and quality of vision (QoV) questionnaires were compared between the 4
      groups for 18 months postoperatively. RESULTS: The study comprised 90 patients
      (180 eyes). The mean preoperative pupil (photopic and mesopic) diameter was 4.3
      mm +/- 0.3 (SD) and 5.6 +/- 1.4 mm, respectively, which decreased to 3.8 +/- 0.7
      mm and 4.9 +/- 1.2 mm, respectively, at 18 months. Eighteen months
      postoperatively, both photopic and mesopic pupil groups had a statistically
      significant reduction in size from preoperative levels. No significant
      differences in UDVA, UIVA, and UNVA were found between the groups (P > .001).
      Significant differences in the QoV questionnaire day scores and night scores were
      found between the 4 groups (P < .001). CONCLUSIONS: The rotationally asymmetric
      multifocal IOL provided excellent optical performance during 18-months follow-up.
      The preoperative photopic pupil is an important parameter for consideration of
      this type of IOL because smaller pupils have a significant negative subjective
      impact on QoV.

PMID- 29223232
TI  - Morphologic features and surgically induced astigmatism of femtosecond laser
      versus manual clear corneal incisions.
AB  - PURPOSE: To compare the morphologic features and surgically induced astigmatism
      (SIA) between laser and manual clear corneal incisions (CCIs) after femtosecond
      laser-assisted cataract surgery. SETTING: Eye Center, 2nd Affiliated Hospital,
      Medical College of Zhejiang University, Hangzhou, China. DESIGN: Prospective case
      series. METHODS: Patients had femtosecond laser-assisted cataract surgery with a
      CCI created with the laser or manually after random allocation. The corrected
      distance visual acuity, corneal topography, and anterior segment optical
      coherence tomography were assessed at the 1-day, 1-week, 1-month, and 3-month
      follow-ups. RESULTS: The laser CCI group comprised 45 eyes and the manual CCI
      group, 48 eyes. The SIA was significantly lower in the manual CCI group than the
      laser CCI group at all visits (P < .05). At the 1-day and 1-week follow-ups, the
      mean CCI thickness was significantly smaller in the manual CCI group (P < .05).
      In the laser CCI group, the perpendicular linear distance between the external
      wound opening and the corneal vertex central line was statistically shorter than
      in the manual CCI group (P < .05). At 3 months, the SIA was correlated with the
      perpendicular linear distance with a Pearson correlation coefficient of -0.341 (P
      = .001). CONCLUSIONS: Femtosecond laser-created CCIs for cataract surgery caused
      more SIA than manually created CCIs, which could have resulted from inaccurate or
      uncertain corneal incision positioning of the femtosecond machine. Manual
      creation of CCIs is recommended in femtosecond laser-assisted cataract surgery
      until the locating system for the femtosecond laser incision is updated.

PMID- 29223233
TI  - Outcomes of retreatment after hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the efficacy, predictability, and safety of laser in situ
      keratomileusis (LASIK) retreatment in eyes with hyperopia. SETTING: Multicenter
      refractive surgery centers and University Hospital, Germany. DESIGN:
      Retrospective case series. METHODS: This multicenter study included hyperopic
      patients with a preoperative difference between cycloplegic and manifest
      refraction of 1.00 diopter (D) or less who had LASIK retreatment based on
      manifest refraction. The refractive outcome was analyzed according to standard
      graphs for reporting the efficacy, predictability, and safety of refractive
      surgery. RESULTS: One hundred thirteen eyes of 113 consecutive hyperopic patients
      were enrolled. Efficacy (P < .001) and safety (P = .004) were statistically
      significantly improved by retreatment without being negatively influenced by
      preoperative manifest spherical equivalent (SE), manifest cylinder, or
      keratometry. In cases still showing a trend toward undercorrection, retreatment
      resulted in 88 eyes (78.0%) being within +/-0.50 D of the attempted correction.
      The optical zone (OZ) diameter of the retreatment did not correlate with
      efficacy, predictability, or safety. CONCLUSIONS: Retreatment after hyperopic
      LASIK resulted in high efficacy, predictability, and safety outcomes. The
      efficacy and safety of the retreatment were not affected by preoperative manifest
      SE, manifest cylinder, keratometry, or OZ diameter.

PMID- 29223234
TI  - Corneal remodeling after implantation of a shape-changing inlay concurrent with
      myopic or hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To compare the induced addition (add)-power profile and epithelial
      remodeling between patients receiving hyperopic and myopic laser in situ
      keratomileusis (LASIK) concurrently with implantation of a corneal shape-changing
      inlay. SETTING: Specialty clinics in Monterrey and Tijuana, Mexico. DESIGN:
      Retrospective case series. METHODS: Preoperative hyperopic patients (mean
      spherical equivalent [SE] treatment +1.71 diopters [D] +/- 0.51 [SD]) and myopic
      patients (mean SE treatment -2.48 +/- 1.33 D) had implantation of a Raindrop Near
      Vision Inlay in the nondominant eye immediately after the excimer laser ablation
      in both eyes under a corneal flap. Monocular and binocular visual acuities were
      recorded at 6 m. Wavefront measurement analysis yielded the mean inlay add-power
      profile, and optical coherence tomography images yielded the mean epithelial
      remodeling profile. RESULTS: In the inlay eye in the hyperopic group (n = 34) and
      myopic group (n = 29), the mean uncorrected near visual acuity exceeded 20/25
      (85% 20/25 or better), the mean uncorrected distance visual acuity (UDVA) was
      20/32 (62% 20/32 or better), and the mean binocular UDVA was 20/18 (100% 20/25 or
      better). The add-power profiles for the hyperopic and myopic groups were similar.
      The epithelial thinning profiles were also the same, thinning centrally by
      approximately 19 MUm, and were uncorrelated with the treated refractive error.
      CONCLUSIONS: After concurrent LASIK and inlay implantation, the visual acuity,
      induced add-power profile, and epithelial remodeling were the same, regardless of
      hyperopic or myopic treatment.

PMID- 29223235
TI  - Determining total corneal power after small-incision lenticule extraction in
      myopic eyes.
AB  - PURPOSE: To evaluate the methods to correct corneal power after myopic small
      incision lenticule extraction (SMILE) and to estimate the preoperative corneal
      power based on postoperative values. SETTING: Tianjin Eye Hospital, Tianjin,
      China. DESIGN: Retrospective case series. METHODS: Equivalent keratometry (K) and
      mean K readings were obtained with the Pentacam HR. The clinical history method
      was used to calculate the theoretical postoperative K, which was then compared
      with equivalent K readings. In addition, the anterior-posterior (A-P) method was
      used to estimate the preoperative mean K. The agreement between computed and
      actual values was estimated using the Bland-Altman method. RESULTS: A significant
      correlation was observed between the theoretical postoperative K (38.52 diopters
      [D] +/- 1.57 [SD]) and mean K after surgery (39.44 +/- 1.43 D) (R2 = 0.9317, P <
      .001). The mean equivalent K readings at 4.0 mm, 4.5 mm, and 5.0 mm were not
      significantly different from the theoretical postoperative K values (P = .620, P
      = .514, and P = .622, respectively). Bland-Altman plots showed a high level of
      agreement when comparing the theoretical postoperative K with the clinical
      history K (-0.94 to +0.9 D, -0.83 to +0.88 D, and -0.84 to +0.88 D,
      respectively). In addition, the estimated preoperative mean K (43.28 +/- 1.31 D)
      derived by the A-P method was comparable to the measured mean K (P = .111).
      CONCLUSIONS: Equivalent K readings provided a relatively good estimation of
      corneal power in eyes after small-incision lenticule extraction. The A-P method
      might be an option to predict preoperative corneal power.

PMID- 29223237
TI  - Effect of chamber stabilization software on efficiency and chatter in a porcine
      lens model.
AB  - PURPOSE: To evaluate the effects of the use of programmable chamber stabilization
      software (Chamber Stabilization Environment) settings on efficiency and chatter
      in a porcine lens model. SETTING: John A. Moran Eye Center Laboratory, University
      of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Porcine
      eyes were dissected and the lenses extracted. The lenses were then hardened and
      processed for the experiment. Phacoemulsification of the lens fragments was
      performed with the Whitestar Signature Pro with the Whitestar handpiece and a 0.9
      mm straight Dewey tip with a 30-degree bevel. All arms of the study were run in
      peristaltic mode with 50 mL/minute aspiration, 100 cm bottle height, and on 100%
      power. The chamber stabilization software setting was used for each of the 4
      study arms with a maximum vacuum of 500 mm Hg. Arm 1 included 20 runs with the up
      time set to 2000 milliseconds. Arm 2 was performed with similar settings but with
      an up time of 0 millisecond. Arms 3 and 4 were run with up times of 1000
      milliseconds and 500 milliseconds, respectively. RESULTS: The mean efficiency
      time of each run was as follows: 0 millisecond = 1.4 seconds, 500 milliseconds =
      0.95 seconds, 1000 milliseconds = 0.88 seconds, 2000 milliseconds = 0.93 seconds.
      When compared with 0 millisecond, each of the other arms were significantly
      faster. Chatter events were comparable between the study arms. CONCLUSION: The
      chamber stabilization software does not decrease efficiency when compared with
      full vacuum on if at least 500 milliseconds of up time is maintained.

PMID- 29223236
TI  - Mechanical outcome of accelerated corneal crosslinking evaluated by Brillouin
      microscopy.
AB  - PURPOSE: To quantify corneal mechanical changes induced by corneal crosslinking
      (CXL) procedures of different ultraviolet-A (UVA) intensity and exposure time
      using Brillouin microscopy. SETTINGS: University of Maryland, College Park,
      Maryland, USA. DESIGN: Experimental study. METHODS: Porcine cornea samples were
      debrided of epithelia and soaked with riboflavin 0.1% solution. Samples were
      exposed to a standard 5.4 J/cm2 of UVA radiation with varying intensity and
      exposure time as follows: 3 mW/cm2 for 30.0 minutes, 9 mW/cm2 for 10.0 minutes,
      34 mW/cm2 for 2.65 minutes, and 50 mW/cm2 for 1.80 minutes. Using Brillouin
      microscopy, the Brillouin modulus for each sample was computed as a function of
      radiation intensity/exposure time. For validation, the Young's modulus was found
      with the stress-strain test and compared at each irradiation condition. RESULTS:
      The standard 3 mW/cm2 irradiance condition produced a significantly larger
      increase in corneal Brillouin modulus than the 9 mW/cm2 (P <= .05), 34 mW/cm2 (P
      <= .01), and 50 mW/cm2 (P <= .01) conditions. Depth analysis showed similar
      anterior sections of the standard and 9 mW/cm2 conditions but significantly less
      stiffening in the central and posterior of the 9 mW/cm2 condition. The stiffening
      of the standard protocol was significantly larger in all sections of the 34
      mW/cm2 and 50 mW/cm2 conditions (P <= .01). The overall change in Brillouin
      derived Brillouin modulus correlated with the increase in Young's modulus (R2 =
      0.98). CONCLUSIONS: At a constant UVA light dose, accelerating the irradiation
      process decreased CXL stiffening. Brillouin analysis showed that accelerated
      protocols were especially ineffective in the deeper portions of the cornea.

PMID- 29223238
TI  - Pupillary block glaucoma secondary to central port occlusion following insertion
      of a phakic implantable copolymer lens.
AB  - A 28-year-old woman had uneventful implantation of a phakic intraocular lens
      (pIOL) in her left eye (Visian ICL, EVO+ model, 13.2, -7.50 diopters) to correct
      myopia. Six days after the procedure, she presented with herniation of the iris.
      Surgical reduction was carried out successfully through the previous peripheral
      corneal paracentesis. On the following day, the patient reported ocular pain and
      blurry vision. Examination showed a shallow anterior chamber, moderate diffuse
      corneal edema, and ocular hypertension. The central port of the pIOL was blocked
      by iris pigment. The condition resolved completely after surgical iridectomy, and
      the postoperative course was uneventful. To our knowledge, this is the first
      reported case of pupillary block after implantation of a pIOL with a central
      hole. This uncommon complication should be taken into consideration when the iris
      is manipulated excessively after pIOL insertion.

PMID- 29223239
TI  - Phacoemulsification with intraocular lens implantation after previous
      descemetorhexis without endothelial keratoplasty.
AB  - A 58-year-old woman with bilateral Fuchs endothelial corneal dystrophy presented
      with predominantly central guttata in the left eye causing visually significant
      stromal edema. A 4.0 mm descemetorhexis without endothelial keratoplasty was
      performed. At the 6-week follow-up, the central cornea had cleared completely and
      the central endothelial cell density (ECD) was 541 cells/mm2. The central corneal
      clearing remained stable for 2 years after the procedure; however, vision
      declined because of a visually significant cataract in the left eye. Uneventful
      phacoemulsification with intraocular lens implantation was performed with a
      target refraction of -0.50 diopters. At 1.5 months postoperatively, the
      uncorrected distance visual acuity was 20/20 with a manifest refraction of -0.25 
      0.25 * 60 and the central ECD was 2373 cells/mm2 (increased from 1471 cells/mm2
      prior to phacoemulsification). Cataract surgery by phacoemulsification years
      after descemetorhexis without endothelial keratoplasty appears to be well
      tolerated, with good clinical and predictive refractive outcomes.

PMID- 29223240
TI  - Easy method for correcting misalignment of a toric phakic intraocular lens using
      vector analysis.

PMID- 29223241
TI  - November consultation #2.

PMID- 29223242
TI  - Decades-old windshield-glass perforating injury with limbal iris incarceration,
      zonular fiber defect, and equatorial lens capsule injury with capsule fibrosis
      and dense cataract: November consultation #1.

PMID- 29223243
TI  - November consultation #3.

PMID- 29223244
TI  - November consultation #4.

PMID- 29223245
TI  - November consultation #5.

PMID- 29223246
TI  - November consultation #6.

PMID- 29223247
TI  - November consultation #7.

PMID- 29223248
TI  - Editor's Comment.

PMID- 29223249
TI  - Population-based analysis of intraocular lens exchange and repositioning.

PMID- 29223250
TI  - Reply.

PMID- 29223251
TI  - Erratum.

PMID- 29223252
TI  - Erratum.

PMID- 29223254
TI  - Lessons from WINGS.

PMID- 29223253
TI  - Erratum.

PMID- 29223255
TI  - Bronchiectasis Management: The State of the Union.

PMID- 29223256
TI  - Prostacyclin Therapy for Pulmonary Arterial Hypertension Evolves Again With the
      Development of an Implantable Delivery System.

PMID- 29223257
TI  - Pulmonary Rehabilitation: The Lead Singer of COPD Therapy but Not a "One-Man
      Band".

PMID- 29223258
TI  - Fifty Years of Monocrotaline-Induced Pulmonary Hypertension: What Has It Meant to
      the Field?

PMID- 29223259
TI  - LESSONS.

PMID- 29223260
TI  - WATCHING OVER ME.

PMID- 29223261
TI  - Exploring the Art of Ciliary Beating: The Benefits of High-Speed Video Analysis.

PMID- 29223262
TI  - Response.

PMID- 29223263
TI  - Optimal Position for Intubation in the ICU: An Uneven Playing Field?

PMID- 29223264
TI  - Pleurodesis.

PMID- 29223265
TI  - Response.

PMID- 29223266
TI  - The Surgical Point of View About Persistent Air Leaks: Prevention First!

PMID- 29223267
TI  - Does the Time of Day a Pulmonary Embolism Response Team Is Activated Affect Time
      to Intervention or Outcome?

PMID- 29223268
TI  - Is Topographic Classification Effective for Lymph Node Metastasis in Patients
      Affected by Non-Small Cell Lung Cancer?

PMID- 29223269
TI  - Response.

PMID- 29223270
TI  - A 40-Year-Old Man With Cough, Shortness of Breath, and Suspected Pleural
      Effusion: "Catastrophe Averted".

PMID- 29223271
TI  - A Woman Admitted to the ED With Severe Acute Respiratory Failure.

PMID- 29223272
TI  - A 49-Year-Old Woman With Right Apical Thoracic Mass.
AB  - A 49-year-old woman with a medical history of essential hypertension presented to
      the ED with severe pain in the left superior chest and dull aching pain in the
      upper flank, lasting for the last 2 days.

PMID- 29223273
TI  - A 79-Year-Old Woman With Dyspnea and Hypoxemia That Worsened in an Upright
      Position.
AB  - CASE PRESENTATION: A 79-year-old woman presented to the ED with complaints of
      gradually worsening exertional dyspnea, dizziness, and chest discomfort. For
      several weeks she had not been able to perform light household work. The
      patient's medical history mentioned pulmonary embolism following immobilization
      (2012), several fractures after trauma, an ischemic cerebral vascular accident
      (2014), and curative treatment for breast cancer (1995). Her current medication
      included esomeprazole, clopidogrel, simvastatin, calcium/vitamin D,
      amitriptyline, and acetaminophen.

PMID- 29223274
TI  - A Woman in Her 60s With Lung Adenocarcinoma Presents With Copious Watery Sputum
      and Respiratory Failure.
AB  - CASE PRESENTATION: A woman in her 60s presented with 1 month of progressive
      dyspnea, watery rhinorrhea, and paroxysmal cough productive of clear, watery
      sputum. She was diagnosed with epidermal growth factor receptor (EGFR) mutation
      positive lung adenocarcinoma at another institution 1 week prior to presentation
      and 3 weeks after the onset of symptoms. She was a never-smoker. She denied
      fevers and had completed a course of antibiotics for presumed pneumonia, without
      clinical improvement. She presented to the hospital due to increasing severity of
      her shortness of breath.

PMID- 29223275
TI  - A 26-Year-Old Man From Mexico With Headaches, Dysuria, and a Right Scrotal Mass.
AB  - CASE PRESENTATION: A 26-year-old man with no medical history was admitted to the
      hospital for evaluation of his change in mental status. He was noted to be
      agitated at work and had difficulty walking for 2 days before being brought in to
      the ED by his family. According to his uncle, the patient had been complaining of
      a headache and pain with urination for approximately 1 week. He was born in
      Guerrero, Mexico (a small farm town), and moved to Los Angeles, California, in
      2008.

PMID- 29223276
TI  - A 51-Year-Old Woman With an Increasing Chest Wall Mass Years After Resection of
      an Early Stage Lung Cancer.
AB  - CASE PRESENTATION: A 51-year-old woman was found to have a new 14 * 6 mm soft
      tissue mass under the right serratus muscle on a CT scan of the chest performed
      for routine surveillance due to her history of stage I lung cancer. A follow-up
      CT scan performed 4 months later showed that the mass had increased in size to 22
      * 8 mm. The patient presents to the oncology clinic to discuss the results of the
      CT scan. She has no pain or swelling on the right lateral chest and no cough,
      fever, or shortness of breath. She is at her baseline health with good appetite
      and functional status.

PMID- 29223277
TI  - [Accuracy in the diagnosis of chronic obstructive pulmonary disease in primary
      care].

PMID- 29223278
TI  - Identification of molecules from non-targeted analysis.

PMID- 29223279
TI  - Circadian and endocrine rhythms.

PMID- 29223280
TI  - Circadian and ultradian patterns of HPA-axis activity in rodents: Significance
      for brain functionality.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis comprises interactions between the
      hypothalamus, the pituitary and the adrenal glands and its activation results in
      the release of corticosteroid hormones. Corticosteroids are secreted from the
      adrenal gland in a distinct 24-h circadian rhythm overarching an ultradian
      rhythm, which consists of hourly corticosteroid pulses exposing target tissues to
      rapidly changing steroid levels. On top of these rhythms surges can take place
      after stress. HPA-axis rhythms promote adaptation to predictable (i.e. the
      earth's rotation) and unpredictable (i.e. stressors) changes in environmental
      factors. Two steroid hormone receptors, the mineralocorticoid receptor (MR) and
      the glucocorticoid receptor (GR), are activated by corticosteroids and mediate
      effects at fast and slow timescales on e.g. glucose availability, gene
      transcription and synaptic plasticity. The current review discusses the origin of
      the circadian and ultradian corticosteroid rhythms and their relevance for gene
      regulation, neuroendocrine and physiological responses to stress and the
      involvement in the maintenance of brain functionality in rodents.

PMID- 29223281
TI  - Human studies on hypothalamo-pituitary-adrenal (HPA) axis.
AB  - The daily rhythm of the hypothalamo-pituitary-adrenal (HPA) axis is regulated by
      the central clock in the suprachiasmatic nucleus. Cortisol, a glucocorticoid,
      acts as a secondary messenger between the central clock and the peripheral
      tissues. Changes in clock time, as seen in shift workers, alters the HPA axis and
      results in metabolic disturbances associated with ill health. Depression,
      anorexia nervosa and obstructive sleep apnoea, are associated with cortisol
      rhythm phase shifts and increased cortisol exposure. Higher nocturnal cortisol
      exposure is observed in patients with Cushing's syndrome and adrenal
      incidentalomas with autonomous cortisol secretion and is associated with insulin
      resistance, and increased cardiovascular risk and mortality. A decrease in
      cortisol rhythm amplitude is seen in adrenal insufficiency, and despite
      replacement, patients have an impaired quality of life and increased mortality.
      Research on cortisol replacement has focused on replacing the cortisol daily
      rhythm by subcutaneous hydrocortisone infusions and oral modified release
      hydrocortisone formulations with the aim of improving disease control and quality
      of life.

PMID- 29223282
TI  - The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of
      TSH's unexpected role using animal models.
AB  - Thyroid hormones (TH) are important for development, growth, and metabolism. It
      is also clear that the synthesis and secretion of TH are regulated by the
      hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our
      understanding of the roles and regulatory mechanisms of TH. The animals' bodies
      develop through coordinated timing of cell division and differentiation. Studies
      of frog metamorphosis led to the discovery of TH and their role in development.
      However, to adapt to rhythmic environmental changes, animals also developed
      various endocrine rhythms. Studies of rodents clarified the neural and molecular
      mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds
      have a sophisticated seasonal adaptation mechanism, and recent studies of quail
      revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the
      seasonal regulation of reproduction. Interestingly, this mechanism is conserved
      in mammals. Thus, we review how animal studies have shaped our general
      understanding of the HPT axis in relation to biological rhythms.

PMID- 29223283
TI  - Regulatory aspects of the human hypothalamus-pituitary-thyroid axis.
AB  - Thyroid hormones are essential for growth, differentiation and metabolism during
      prenatal and postnatal life. The hypothalamus-pituitary-thyroid (HPT)-axis is
      optimized for these actions. Knowledge of this hormonal axis is derived from
      decades of experiments in animals and man, and more recently from spontaneous
      mutations in man and constructed mutations in mice. This review examines the HPT
      axis in relation to 24 h TSH profiles in men in various physiological and
      pathophysiological conditions, including obesity, age, longevity, and primary as
      well as central hypothyroidism. Hormone rhythms can be analyzed by quantitative
      methods, e.g. operator-independent deconvolution, approximate entropy and fitting
      the 24-h component by Cosinor analysis or related procedures. These approaches
      have identified some of the regulatory components in (patho)physiological
      conditions.

PMID- 29223284
TI  - Daily rhythms count for female fertility.
AB  - Female ovulation depends on a surge in circulating luteinizing hormone (LH) which
      occurs at the end of the resting period and requests high circulating estradiol.
      This fine tuning involves both an estradiol feedback as an indicator of oocyte
      maturation, and the master circadian clock of the suprachiasmatic nuclei as an
      indicator of the time of the day. This review describes the mechanisms through
      which daily time cues are conveyed to reproductive hypothalamic neurons to time
      the pre-ovulatory surge. In female rodents, neurotransmitters released by the
      suprachiasmatic nuclei activate the stimulatory kisspeptin neurons and reduce the
      inhibitory RFRP neurons precisely at the end of the afternoon of proestrus to
      allow a full surge in LH secretion. From these findings, the impact of circadian
      disruptions (during shift or night work) on female reproductive performance and
      fertility should now being investigated in both animal models and humans.

PMID- 29223285
TI  - Editorial overview: Seeds for a bioenergy future.

PMID- 29223286
TI  - Editorial overview: How to generate molecular diversity, the most important
      process in biology.

PMID- 29223287
TI  - Abdominal splenosis: Usefulness of 99mTc-phytate hepato-splenic scintigraphy in
      the differential diagnosis with tumor implantation.

PMID- 29223288
TI  - Prediction of Delayed Atrioventricular Block and Pacemaker Implantation After
      Transcatheter Aortic Valve Replacement With CoreValve.

PMID- 29223289
TI  - Frequency and Consequences of Right-Sided Heart Failure After Continuous-Flow
      Left Ventricular Assist Device Implantation.
AB  - Postoperative right-sided heart failure (RHF) is a common complication after
      continuous-flow left ventricular assist device implantation. Studies have
      examined RHF in the perioperative period, but few have assessed late-onset RHF.
      We analyzed the incidence of early and late RHF in patients with HeartMate II and
      HeartWare left ventricular assist devices and associated morbidity, mortality,
      and independent predictors of RHF. We retrospectively analyzed records of 526
      patients with chronic heart failure who underwent continuous-flow left
      ventricular assist device implantation; 147 (27.9%) developed RHF (early RHF, n =
      87, 16.5%; late RHF, n = 74, 14.4%). We examined demographics, postoperative
      complications, and long-term survival rate. Patients with RHF or late RHF had
      higher mortality (p <0.001) than those without RHF. Patients with RHF had a
      higher incidence of acute kidney injury (20.4% vs 11.9%, p = 0.01). Device type
      did not affect the incidence of early, late, or overall RHF. Patients with severe
      RHF requiring right ventricular assist device support had a low success of bridge
      to transplantation (11.1% vs 33.3%, p = 0.02). In Cox regression models, RHF was
      an independent predictor of mortality (hazard ratio = 1.69, 95% confidence
      interval = 1.28 to 2.22, p <0.001), but no predictive variables of RHF were
      identified. RHF was significantly associated with increased mortality and a
      higher incidence of postoperative acute kidney injury. RHF decreased the success
      rate of bridging patients to transplantation when a right ventricular assist
      device was required.

PMID- 29223290
TI  - Clinical research at territorial section meetings of the Spanish Academy of
      Dermatology and Venereology (AEDV).
AB  - INTRODUCTION: Clinical research is the study of patients with the aim of
      improving care. Our objectives were to calculate the percentage of presentations
      at territorial section meetings of the Spanish Academy of Dermatology and
      Venereology (AEDV) that described clinical research, to assess the level of
      evidence the research provided, and to analyze change in clinical research volume
      over time. MATERIAL AND METHODS: We reviewed supplements of the journal Actas
      Dermo-Sifiliograficas for 2000 through 2015 that contained abstracts of
      presentations given at the AEDV section meetings in Galicia; the area comprising
      Asturias, Cantabria, and Castile-Leon (ACCL); and Andalusia. We selected
      abstracts that met a previously validated definition of clinical research and
      categorized each according to level of evidence. We also analyzed how the weight
      of clinical research presentations changed over time. RESULTS: Of the total of
      1,188 presentations, 29.6% met the criteria that defined clinical research. Most
      provided level-4 evidence (95.2%); 44.2% of those presentations reported cross
      sectional studies and 55.8% analyzed case series. Clinical research accounted for
      26.6% of the presentations in Galicia (94.7% of them, level 4), 22.7% of those at
      the ACCL meeting (97.6%, level 4), and 37.2% of those in Andalusia (94.3%, level
      4). The proportion of clinical research increased significantly over the years
      studied. CONCLUSIONS: Clinical research accounted for 29.6% of the communications
      presented at the meetings we reviewed. Most of these presentations concerned case
      series or cross-sectional studies. The prevalence of clinical research
      presentations differed between the 3 territories studied, but the levels of
      evidence were similar. The proportion of clinical research in the programs of
      these meetings has increased over time.

PMID- 29223291
TI  - Reply.

PMID- 29223292
TI  - Can we refine body mass estimations based on femoral head breadth?
AB  - Femoral head breadth is widely used in body mass estimation in biological
      anthropology. Earlier research has demonstrated that reduced major axis (RMA)
      equations perform better than least squares (LS) equations. Although a simple RMA
      equation to estimate body size from femoral head breadth is sufficient in most
      cases, our experiments with male skeletons from European data (including late
      Pleistocene and Holocene skeletal samples) and the Forensic Anthropology Data
      Bank data (including the W. M. Bass Donated Skeletal Collection sample) show that
      including femoral length or anatomically estimated stature in an equation with
      femoral head breadth improves body mass estimation precision. More specifically,
      although directional bias related to body mass is not reduced within specific
      samples, the total estimation error range, directional bias related to stature,
      and temporal fluctuation in estimation error are markedly reduced. The overall
      body mass estimation precision of individuals representing different temporal
      periods and ancestry groups (e.g., African and European ancestry) is thus
      improved.

PMID- 29223293
TI  - Gradient measurements of gaseous elemental mercury (Hg0) in the marine boundary
      layer of the northwest Sea of Japan (East Sea).
AB  - Gaseous elemental mercury (Hg0) is a prolific and persistent contaminant in the
      atmosphere. Atmospheric concentrations of Hg0 were determined from 17 September
      to 7 October 2015 in the northwest Sea of Japan aboard the Russian research
      vessel Professor Gagarinsky. Simultaneous measurements of Hg0 concentrations were
      performed 2 m and 20 m above the sea surface using automatic Hg0 analysers RA
      915M and RA-915+, respectively. Concentrations ranged from 0.3 to 25.9 ng/m3 (n =
      5207) and from 0.3 to 27.8 ng/m3 (n = 4415), with medians of 1.7 and 1.6 ng/m3,
      respectively. Elevated Hg0 was observed during three episodes from 19 to 22
      September, likely caused by one or more of the following factors: 1) atmospheric
      transport of Hg0 from the west and south-west (from N. Korea, China, and the
      Yellow Sea region); 2) Hg0 emission from the sea due to pollution by water from
      the Tumannaya River; or 3) underwater geological activities. Increased Hg0
      concentration was observed during periods when air masses flowed from the south,
      and low concentrations were observed when air masses came from the north. A
      daytime increase of Hg0 concentrations at a height of 2 m occurred simultaneously
      with decreasing Hg0 at a height of 20 m. These diurnal variations suggest that
      two contrasting processes occur during the daytime in the marine boundary layer
      (MBL): Hg0 emission from the sea surface and Hg0 oxidation in the MBL by active
      halogens formed by photolysis.

PMID- 29223294
TI  - Glucocorticoid hormone treatment enhances the cytokine production of regulatory T
      cells by upregulation of Foxp3 expression.
AB  - OBJECTIVE: Despite the fact that glucocorticoids (GC) are important therapeutic
      tools, their effects on regulatory T cells (Treg) are not well defined. The aim
      of our work was to investigate how GCs influence in vivo the thymic (tTreg) and
      peripheral Treg (pTreg) differentiation, survival and cytokine production.
      METHODS: Tregs were detected with flow cytometry in lymphatic organs of 4-6 weeks
      old BALB/c mice after repeated (2-4days), high-dose in vivo GC treatment using
      CD4/CD25 cell surface and Foxp3/IL-10/TGFbeta/glucocorticoid receptor (GR)
      intracellular staining. Cytokine, Foxp3, and GR mRNA levels of sorted
      CD4+CD25high T cells were analyzed using RT-PCR. Foxp3 and GR localization in
      Treg cells was investigated with confocal microscopy. RESULTS: GC treatment of
      mice resulted in increased relative tTreg frequency in the thymus, which was due
      to decreased total thymocyte numbers with unchanged absolute tTreg cell count. In
      contrast the relative pTreg cell ratio in secondary lymphatic organs decreased or
      showed no changes after GC treatment, while the absolute number of pTregs
      decreased. Elevated intracellular IL-10+ and TGFbeta+ tTreg and pTreg ratios were
      measured in GC-treated animals, accompanied with elevated Foxp3 mRNA expression.
      In addition, GC treatment caused increased TGFbeta and IL-35 mRNA expression in
      CD4+CD25high+ splenic and elevated IL-10 mRNA level in thymic tTregs. GR
      expression of thymic tTreg cells was lower than in pTregs. GC treatment caused an
      opposite change in GR levels, elevating GR in tTregs but decreasing it in pTregs.
      We observed a nuclear localization of GR in both tTregs and pTregs, which showed
      high colocalization (~60%) with Foxp3 transcription factor. These data suggest an
      interaction of these two transcription factors with further increase due to GC
      treatment in splenic pTregs. CONCLUSION: Our data show selective survival of
      tTregs and elevated production of immunosuppressive cytokines by Treg cells after
      GC treatment, which may contribute to the immunosuppressive effects of GCs.

PMID- 29223295
TI  - Could calcium channel blockers treat 2 illnesses with 1 pill?

PMID- 29223296
TI  - Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated
      patients in PROSPERO.

PMID- 29223297
TI  - Increasing our knowledge base of asthma.

PMID- 29223299
TI  - Burden of skin pain in atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is associated with itch, skin inflammation and
      barrier disruption, and scratching, all of which may be associated with skin
      pain. OBJECTIVE: To characterize the patient burden of skin pain in AD. METHODS:
      We performed a prospective dermatology practice-based study using questionnaires
      and evaluation by a dermatologist. RESULTS: Overall, 305 patients (age range, 13
      97 years) were included in the study, with 564 encounters. The cohort included
      195 females (63.9%) and 193 whites (63.7%). The mean (SD) age at enrollment was
      42.3 (18.1) years, and the mean (SD) age of patient-reported AD onset was 29.6
      (31.9) years. At baseline, 144 patients (42.7%) reported skin pain in the past
      week, with 42 (13.8%) reporting severe or very severe pain. Twenty-four (16.8%)
      thought the skin pain was part of their itch, 16 (11.2%) from scratching, and 77
      (72.0%) from both. Patients with skin pain were more likely to describe their
      itch using terms that resembled neuropathic pain. Prevalence of skin pain was
      increased in patients with vs without excoriations (72.6% vs 57.6%; chi2 test P =
      .02) but not other morphologic characteristics. Skin pain severity was most
      strongly correlated with the Patient-Oriented Eczema Measure (Spearman rho =
      0.54), followed by ItchyQOL (rho = 0.52), 5-dimensions of itch scale (rho =
      0.47), Dermatology Life Quality Index (rho = 0.45), numeric rating scale for itch
      (rho = 0.43) and sleep (rho = 0.36), Patient Health Questionnaire 9 (rho = 0.36),
      patient-reported global AD severity (rho = 0.34), Eczema Area and Severity Index
      (rho = 0.23), and objective Scoring AD index (rho = 0.20) (P < .001 for all).
      Patients with both severe itch and pain vs those with only one or neither symptom
      being severe had significant increases in all these measures. CONCLUSION: Skin
      pain is a common and burdensome symptom in AD. Skin pain severity should be
      assessed with itch severity in AD patients and may be an important end point for
      monitoring treatment response.

PMID- 29223300
TI  - Toxocara species exposure, symptoms of asthma, and fractional exhaled nitric
      oxide in the US population.

PMID- 29223301
TI  - Spectrum and prevalence of reactions to marijuana in a Colorado allergy practice.

PMID- 29223298
TI  - Innate lymphoid cells and allergic disease.

PMID- 29223302
TI  - Modeling the target dose fall-off in IMRT and VMAT planning techniques for
      cervical SBRT.
AB  - There has been growing interest in the use of stereotactic body radiotherapy
      (SBRT) technique for the treatment of cervical cancer. The purpose of this study
      was to characterize dose distributions as well as model the target dose fall-off
      for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc
      therapy (VMAT) delivery techniques using 6 and 10 MV photon beam energies.
      Fifteen (n = 15) patients with non-bulky cervical tumors were planned in
      Pinnacle3 with a Varian Novalis Tx (HD120 MLC) using 6 and 10 MV photons with the
      following techniques: (1) IMRT with 10 non-coplanar beams (2) dual, coplanar 358
      degrees  VMAT arcs (4 degrees  spacing), and (3) triple, non-coplanar VMAT arcs.
      Treatment volumes and dose prescriptions were segmented according to University
      of Texas Southwestern (UTSW) Phase II study. All plans were normalized such that
      98% of the planning target volume (PTV) received 28 Gy (4 fractions). For the
      PTV, the following metrics were evaluated: homogeneity index, conformity index,
      D2cc, Dmean, Dmax, and dose fall-off parameters. For the organs at risk (OARs),
      D2cc, D15cc, D0.01cc, V20, V40, V50, V60, and V80 were evaluated for the bladder,
      bowel, femoral heads, rectum, and sigmoid. Statistical differences were evaluated
      using a Friedman test with a significance level of 0.05. To model dose fall-off,
      expanding 2-mm-thick concentric rings were created around the PTV, and doses were
      recorded. Statistically significant differences (p < 0.05) were noted in the dose
      fall-off when using 10 MV and VMAT3-arc, as compared with IMRT. VMAT3-arc
      improved the bladder V40, V50, and V60, and the bowel V20 and V50. All fitted
      regressions had an R2 >= 0.98. For cervical SBRT plans, a VMAT3-arc approach
      offers a steeper dose fall-off outside of the target volume. Faster dose fall-off
      was observed in smaller targets as opposed to medium and large targets, denoting
      that OAR sparing is dependent on target size. These improvements are further
      pronounced with the use of 10-MV photons.

PMID- 29223303
TI  - Influence of body habitus on dose parameters of nodal levels III to IV
      irradiation for breast cancer: comparison of 3 techniques.
AB  - This study aimed to investigate the effect of body habitus on supraclavicular
      (SC) dose-volume histogram (DVH) parameters among breast cancer patients
      according to 3 different techniques. Three SC irradiation plans were generated
      for 24 postoperative breast cancer patients: (1) direct antero-posterior field
      only (1fieldP), with dose prescribed to a 3-cm depth; (2) 3-cm depth plan (3cmP)
      using an antero-posterior field plus a posterior boost with the dose prescription
      defined to 3 cm; and (3) optimized plan (OptP) similar to 3cmP, with dose
      prescribed depending on the anatomy. The OptP plans had the least variation in
      DVH parameters with body habitus; 3cmP plans were the most varied. Conformity
      index among normal weight patients were 0.73, 0.78, and 0.87 (p = 0.02) and 0.61,
      0.6, and 0.82 among overweight-obese patients for 1fieldP, 3cmP, and OptP,
      respectively (p < 0.001). V95% of the planning target volume among normal weight
      patients were 72.63%, 78.03%, and 87.18% for 1fieldP, 3cmP, and OptP,
      respectively (p = 0.02). The corresponding values among overweight-obese patients
      were 60.5%, 59.62%, and 81.62%, respectively (p = 0.001). Fixed depth dose
      prescriptions caused greater SC under dose than plans optimized according to
      patient's anatomy.

PMID- 29223304
TI  - The relationship between perceived gender judgment and well-being among surgical
      residents.
AB  - BACKGROUND: Physician well-being is a significant problem. Here we explore
      whether one factor, a resident's concern for being judged by one's gender,
      influences well-being. METHODS: Over two years at one institution, we surveyed
      surgical residents on validated measures of well-being as well as the extent to
      which they felt they were judged because of their gender (gender judgment). We
      used correlations and linear regression to investigate the relationships between
      gender judgment and well-being. RESULTS: There were 193 unique respondents (87%
      response rate). Women had significantly more concerns about gender judgment than
      men (M = 2.39, SD = 0.73 vs. M = 1.46, SD = 0.62, t = -9.47, p < 0.00001). In
      regression analyses, gender judgment concerns were significantly associated with
      all three well-being outcomes (Bs -0.34, 0.50, and 0.39, respectively for well
      being, emotional exhaustion, and depersonalization, all p < 0.013). CONCLUSIONS:
      The degree to which residents, both male and female, are concerned about being
      judged for their gender is significantly associated with worse well-being.

PMID- 29223305
TI  - Usefulness of ultra-high resolution mapping for detecting epicardial atrial
      activation during mitral isthmus ablation.
AB  - We describe a patient with perimitral atrial flutter (PMF) following the atrial
      fibrillation ablation and the linear ablation at the mitral isthmus (MI). From
      both the activation and the voltage maps using ultra-high resolution mapping, we
      detected the epicardial connection through the coronary sinus (CS) within the
      entire reentrant circuit. Point ablation within the CS, not additional linear MI
      ablation from the endocardium terminates PMF, with a bidirectional block across
      the low voltage area at the MI.

PMID- 29223306
TI  - Diagnostic accuracy of multi-lead ECGs obtained using a pocket-sized bipolar
      handheld event recorder.
AB  - BACKGROUND: Handheld ECG event recorders are useful for rhythm monitoring but
      only record a single lead, which may limit interpretation. We sought to
      investigate if a multi-lead ECG may be reconstituted using this device, and aimed
      to evaluate diagnostic accuracy. METHODS: A commercially-available handheld
      bipolar ECG event recorder was used to reconstruct a 9-lead ECG (leads I, II and
      III, V1-6). Tracings were analyzed independently by a cardiologist and a fellow.
      RESULTS: A total of 52 patients were evaluated. Accuracy was excellent (85-98%)
      for identifying atrial fibrillation, atrioventricular block, bundle branch block
      and left ventricular hypertrophy, but lower (77-88%) for ST-segment changes and
      prolonged QTc. CONCLUSIONS: A 9-lead ECG can be reconstituted using a handheld
      single-lead ECG event recorder, and provides good diagnostic accuracy for common
      findings.

PMID- 29223307
TI  - Assessment of the innate immune response in the periparturient cow.
AB  - The transition period is the most critical phase in the life of high yielding
      dairy cows. Within a few weeks, cows are submitted to many challenges
      (physiological, nutritional, psychological, management) that require prompt and
      effective adaptive responses. The immune system is involved in this process, and
      many changes of the cow's immune system components have been observed around
      calving. Cows are considered to be immunosuppressed in late lactation, and
      available data suggest that the immune system is dysregulated around parturition.
      Significant attention has been focused on modification of cellular functions
      (e.g. the reduction of phagocytosis and diapedesis), but growing interest
      concerns the components of the innate immune system, which often exhibits
      increased responses such as susceptibility to inflammatory events and the related
      acute phase response (APR). Systemic inflammation plays a significant role in
      early lactation, affects many liver functions and has been associated with the
      impairment of cow performance (i.e. reduced feed intake, milk yield, fertility,
      welfare). The assessment of variations in immune-metabolic indices offers
      opportunities to predict the onset of the health troubles and to anticipate the
      proper therapies needed to guarantee health, good welfare and fertility in the
      following lactation. The frequency of diseases (metabolic and infectious) before
      calving is rare, but several clues suggest that various metabolic and immune
      variations can begin during the dry period. Interesting preliminary results
      encourage this perspective and possible candidates are suggested.

PMID- 29223309
TI  - Improving Quality of Life for Oral Cancer Patients.

PMID- 29223308
TI  - What we have lost: Mastitis resistance in Holstein Friesians and in a local
      cattle breed.
AB  - In Holstein Friesian dairy cows, selective pressure for increased milk production
      has led to a higher propensity to disease, including mastitis, when compared to
      less selected and lower producing dairy breeds. The biology underpinning the
      higher resistance to disease of such "local breeds" is not fully understood. With
      the aim of investigating the factors associated to this phenomenon, we applied a
      multidisciplinary approach to compare innate immune response patterns, metabolic
      parameters, milk protein profiles and the milk microbiota in Holstein Friesian
      and Rendena cows reared in the same farm and under the same management
      conditions. Quarter milk samples and blood plasma were collected from all cows at
      dry-off, 1day after calving, 7-10days after calving and 30days after calving.
      Quarter milk samples were subjected to bacteriological culture, characterization
      of the milk microbiota by 16S metagenomics, milk protein profiling by
      electrophoresis and densitometry, somatic cell counting, measurement of the
      inflammation marker cathelicidin and assessment of different innate immune
      related mediators such as lysozyme, CD45, IL-1beta, TNF-alpha, PTX3, IL-1R8. In
      parallel, the main inflammometabolic parameters were measured in blood plasma
      samples. Despite having relatively few animals (6 moderate-yielding Holstein
      Friesian and 4 low-yielding Rendena) some important differences were apparent.
      Holstein Friesian cows showed a more severe fat mobilization and systemic
      inflammatory response postpartum in comparison with Rendena cows, which had a
      greater postpartum muscle mass and an increased amino acid mobilization compared
      to Holstein Friesians. Upon bacteriological analysis, contagious bacteria such as
      Staphylococcus aureus and Streptococcus agalactiae were absent, but significant
      differences were seen in the general composition of the milk microbiota of the
      two breeds. Concerning the milk protein abundance profile, pronounced differences
      were seen in colostrum, with significantly higher amounts of immunoglobulins and
      other immune-related proteins in Rendena. Added to this, the expression of innate
      immune related genes such as PTX-3, IL-1beta, TNF-alpha, and KRT5 expression in
      milk epithelial and leukocyte cell components, respectively, was lower in
      Holstein Friesian colostrum compared with Rendena. In conclusion, several
      differences were observed in the two breeds, in spite of the same farming
      conditions. The observations reported in this work present numerous pointers to
      the factors that may provide autochthonous, more rustic breeds with a higher
      resistance to disease.

PMID- 29223310
TI  - Cystinuria: One Possible Reason for Kidney and Salivary Gland Lithiasis
      Relationship.
AB  - Salivary gland lithiasis affects 1 to 2% of adults. The submandibular glands are
      concerned in 87% of cases. An association between kidney and salivary lithiases,
      although often mentioned, has rarely been observed. We relate an exceptional case
      of parotid and submandibular cystine sialolithiasis with kidney cystine lithiasis
      in a patient with cystinuria. Cystine lithiasis occurs in 1% of kidney lithiasis
      cases. The purpose of this article is to discuss the arguments, diagnosis, and
      therapeutic attitude in front of salivary cystine lithiasis. The patient was a 56
      year-old woman treated for cystinuria undergoing a consultation for parotid
      lithiases. We obtained a panoramic view and performed a cervicofacial computed
      tomography scan, sialo-magnetic resonance imaging, and sialendoscopy. We found
      multiple lithiases in the distal portions of the Stensen duct, and 2 days after
      sialendoscopy, the patient expelled small sialoliths. Salivary lithiasis in
      patients with cystinuria has the same biochemical composition as kidney
      lithiasis. A computed tomography scan is efficient in most cases, but sialo
      magnetic resonance imaging may be the only noninvasive method to diagnose small
      cystine salivary lithiases, such as those that can be seen in patients with
      cystinuria. Sialendoscopy is still an efficient diagnostic and therapeutic method
      for every type of salivary lithiasis.

PMID- 29223311
TI  - A Comparative Clinical Evaluation of the Buccal Fat Pad and Extended Nasolabial
      Flap in the Reconstruction of the Surgical Defect in Oral Submucous Fibrosis
      Patients.
AB  - PURPOSE: The aim of this study was to compare the efficacy of locally available
      nasolabial and buccal fat pad flaps for increasing postoperative mouth opening in
      the reconstruction of the defect created after fiberotomy in surgically treated
      cases of oral submucous fibrosis (OSMF). MATERIALS AND METHODS: Of 32 patients
      selected for the study, 21 patients underwent closure of the surgical defect
      using the buccal fat pad (group 1) and 11 patients underwent closure of the
      surgical defect using a nasolabial flap (group 2). Histologically proven cases of
      OSMF with a mouth opening no larger than 25 mm were included in the study.
      Patients in groups 1 and 2 were evaluated at regular intervals and mouth opening
      was documented preoperatively, intraoperatively, and at 3 and 6 months of follow
      up. The results were analyzed by paired and unpaired t tests. RESULTS: In groups
      1 and 2, mouth opening differed substantially at all periods of follow-up from
      preoperative values. At 3-month follow-up, mean mouth opening increased to 32.41
      mm in group 2 compared with 30.47 in group 1. No relevant difference was observed
      in mouth opening between groups 1 and 2 at the end of 6 months. The effective
      increase in mouth opening at the end of 6 months compared with the preoperative
      value was statistically different in group 2 (mean increase, 24.2 mm) compared
      with group 1 (mean increase, 19.2 mm). CONCLUSION: Nasolabial flaps are a good
      option for the coverage of surgically treated defects in OSMF compared with the
      buccal fat pad.

PMID- 29223312
TI  - Bioprinting for Neural Tissue Engineering.
AB  - Bioprinting is a method by which a cell-encapsulating bioink is patterned to
      create complex tissue architectures. Given the potential impact of this
      technology on neural research, we review the current state-of-the-art approaches
      for bioprinting neural tissues. While 2D neural cultures are ubiquitous for
      studying neural cells, 3D cultures can more accurately replicate the
      microenvironment of neural tissues. By bioprinting neuronal constructs, one can
      precisely control the microenvironment by specifically formulating the bioink for
      neural tissues, and by spatially patterning cell types and scaffold properties in
      three dimensions. We review a range of bioprinted neural tissue models and
      discuss how they can be used to observe how neurons behave, understand disease
      processes, develop new therapies and, ultimately, design replacement tissues.

PMID- 29223313
TI  - Society of Pediatric Nurses' Core Competencies for the Pediatric Nurse.

PMID- 29223314
TI  - Child Physical Abuse, Non-anemic Iron Deficiency and Behavior Problems.
AB  - PURPOSE: Child abuse is regarded as a life-course social determinant of health
      problems. However, little is known about the nutritional status of physically
      abused children and their cumulative effect on child behavior. The present study
      aimed to examine the non-anemic iron deficiency status of abused children and the
      combined effect of physical abuse and non-anemic iron deficiency on child
      behavior in China. METHODS: This cross-sectional study comprised 314 children
      aged 11-14 (12.30+/-0.57) years old from Jintan, China. Children self-reported
      their physical abuse experiences and behavior problems. Blood iron and hemoglobin
      concentrations were also measured. RESULTS: Thirty-eight percent of children
      reported physical abuse experience, 17.5% had non-anemic iron deficiency, and the
      two risk factors co-occurred in 8.0% children. Physically abused children were
      more likely to be affected by non-anemic iron deficiency than their non-abused
      counterparts. Children who had experienced both physical abuse and non-anemic
      iron deficiency reported more behavior problems than children with neither or
      either risk factors. CONCLUSIONS: Physically abused children are more likely to
      have non-anemic iron deficiency. Children with the presence of both physical
      abuse experience and non-anemic iron deficiency have more behavior problems.
      There is a need to prevent both child abuse and non-anemic iron deficiency
      simultaneously to maintain normal child behavior development.

PMID- 29223315
TI  - Metal free, full arch, fixed prosthesis for edentulous mandible rehabilitation on
      four implants.
AB  - PURPOSE: The goal of this work is to describe an implant-prosthetic protocol for
      rehabilitation of edentulous mandible, by using a fixed prosthesis made of fiber
      reinforced composite material (FRC). The protocol contemplates a minimal invasive
      surgery and ensures predictable and safe results, with good aesthetic and
      performance combined to cost savings. METHODS: FRC material is used to build the
      substructure of a prosthetic framework supported by four short implants (5mm long
      and 4mm wide). The prosthesis substructure is made of Trinia immersed in a matrix
      of epoxy resin (FRC). It is supplied in milling blocks (pre-cured) for the
      CAD/CAM (computer-aided design/computer-aided manufacturing) technique. Implants
      are placed in lower edentulous jaw in position of first molar and canine, each
      side. Four month after, a resin bar is build based on a stone model, denture
      teeth are placed and the occlusion is checked. The resin bar and the stone model
      with milled abutments are scanned and a FRC bar is achieved with the CAD/CAM
      technique. The teeth are mounted to the substructure trough denture resin.
      Temporary cementation of framework is achieved on the abutments connected to the
      implants. CONCLUSION: A protocol for a fixed mandibular implant-prosthetic
      rehabilitation is described. The protocol contemplates a minimal invasive surgery
      and ensures predictable and safe results, with good aesthetic and performance
      combined to cost savings. In addition, this technique allows performing basic
      surgery also in presence of atrophy.

PMID- 29223316
TI  - A case of human ocular dirofilariasis in a patient with multiple endocrine
      neoplasia in Northwest Spain.

PMID- 29223317
TI  - Sequential strategy for the LTBI screening of newly-arrived immigrants in
      vulnerable social situations.
AB  - INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis
      infection (LTBI) in the immigrant population, which is relevant because 5-10% of
      cases will develop active tuberculosis. The objective of this study is to
      describe the results of a sequential strategy in the newly-arrived immigrant
      population for the diagnosis of LTBI using the tuberculin skin test (TST) and
      IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants
      between 6 and 35years of age from shelters, referred to an international health
      unit between July 2013 and June 2016. The TST was performed and when it was
      >=5mm, IGRAs were conducted. LTBI was defined as an IGRA >=0.35IU/ml and normal
      chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age.
      The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from
      Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was >=10mm in 79
      cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184
      (17.9%). Cohen's Kappa index (between TST>=10mm and IGRAs) was 0.226. CONCLUSION:
      Basing LTBI screening on the TST alone could give rise to an overestimation. Some
      studies show that sequential screening would be the most cost-effective; this
      seems most evident in BCG-vaccinated populations.

PMID- 29223318
TI  - A 7-year-old boy with preseptal cellulitis of torpid evolution.

PMID- 29223319
TI  - Tuberculosis in immunosuppressed patients.
AB  - Tuberculosis (TB) is one of the most significant infections in immunosuppressed
      patients due to its high frequency and high morbidity and mortality. TB is the
      leading cause of death among HIV-infected patients. The diagnosis and early
      treatment of latent tuberculosis infection is vital to preventing it progression
      to disease. Similarly, the early diagnosis of TB is key to improving the
      prognosis of patients and preventing its transmission. The clinical expression of
      TB in immunosuppressed patients is conditioned by the patient's degree of
      immunosuppression. It is important to keep this peculiarity in mind so as not to
      delay the diagnosis of suspected TB. TB treatment is basically the same in
      immunosuppressed patients as in the general population and any differences mainly
      derive from pharmacological interactions. We examined the diagnosis and treatment
      of TB and latent tuberculosis infection in immunosuppressed patients.

PMID- 29223320
TI  - Between-session and within-session intra-individual variability in attention in
      aphasia.
AB  - Persons with aphasia (PWA) have been found in many previous studies to exhibit
      impaired performance on attention processing tasks, even when these tasks do not
      contain linguistic stimuli. There is also some evidence that as individuals, PWA
      may show more intra-individual variability (i.e. time-based fluctuations) in
      attention than healthy controls. The current study systematically examines two
      types of intra-individual variability in attention in aphasia, between-session
      intra-individual variability (BS-IIV) and within-session intra-individual
      variability (WS-IIV), looking in particular at how task demands impact these
      dimensions of performance. We administered five novel attention tasks with
      varying processing demands, three non-linguistic and two linguistic, to 20 PWA
      and 20 similar-aged healthy controls. Results showed that PWA exhibited higher
      levels of WS-IIV than controls but that levels of BS-IIV were similar between the
      two groups. Increased task demands were found to result in increased BS-IIV and
      WS-IIV for both groups, and there was some evidence suggesting that the addition
      of language demands may further increase both WS-IIV and BS-IIV in the PWA group.
      In addition to these group differences, substantial inter-individual variability
      in WS-IIV and BS-IIV was observed within the PWA group. These findings have
      implications for better understanding attentional fluctuations in aphasia, as
      well as how it relates to language deficits in this population, and potentially
      for better understanding language treatment outcomes.

PMID- 29223321
TI  - Is there value in retrospective 90-day bundle payment models for shoulder
      arthroplasty procedures?
AB  - BACKGROUND: The Centers for Medicare & Medicaid Services Bundled Payments for
      Care Improvement (BPCI) initiative was implemented as part of the Affordable Care
      Act. We implemented a retrospective payment model 2 for a 90-day total shoulder
      arthroplasty (TSA) episode to assess the value of TSA BPCI at our private
      practice. METHODS: Expenditures and postacute event rates of 132 fee-for-service
      (FFS) patients who underwent a TSA operation between 2009 and 2012 were compared
      with 333 BPCI patients who had a TSA operation in 2015. The 90-day postacute
      events included an inpatient rehabilitation facility (IRF), skilled nursing
      facility (SNF), and home health (HH) admissions and readmissions. Expenditures
      were converted to 2016 dollars using the Consumer Price Index. Wilcoxon tests and
      multivariate generalized estimating equation were used to assess independent cost
      drivers. RESULTS: The median FFS expenditure was $21,157 (interquartile range,
      $16,894-$30,748) compared with $17,894 (interquartile range, $15,796-$20,894) for
      BPCI (P < .0001). The BPCI patients had significantly lower rates of SNF
      admissions (34% FFS vs. 16% BPCI; P < .001), IRF admissions (3% FFS vs. 0.6%
      BPCI; P = .05), HH utilization (49% FFS vs. 41% BPCI; P = .05), and readmissions
      (14% FFS vs. 7% BPCI; P = .01). After controlling for postacute events in the
      multivariate regression model, we found BPCI had a 4% decrease in expenditures (P
      = .08). All postacute events were independently associated with higher
      expenditures. CONCLUSIONS: Our private practice implemented cost-containment
      practices, including clinical guidelines, patient navigators, and a BPCI
      management team. IRF and SNF utilization and the 90-day readmission rate
      significantly decreased. As a result, we were able to control the postacute
      spending, which resulted in decreased costs of performing TSA surgery.

PMID- 29223322
TI  - Systemic administration of epothilone D improves functional recovery of walking
      after rat spinal cord contusion injury.
AB  - Central nervous system (CNS) injuries cause permanent impairments of sensorimotor
      functions as mature neurons fail to regenerate their severed axons. The poor
      intrinsic growth capacity of adult CNS neurons and the formation of an inhibitory
      lesion scar are key impediments to axon regeneration. Systemic administration of
      the microtubule stabilizing agent epothilone B promotes axon regeneration and
      recovery of motor function by activating the intrinsic axonal growth machinery
      and by reducing the inhibitory fibrotic lesion scar. Thus, epothilones hold
      clinical promise as potential therapeutics for spinal cord injury. Here we tested
      the efficacy of epothilone D, an epothilone B analog with a superior safety
      profile. By using liquid chromatography and mass spectrometry (LC/MS), we found
      adequate CNS penetration and distribution of epothilone D after systemic
      administration, confirming the suitability of the drug for non-invasive CNS
      treatment. Systemic administration of epothilone D reduced inhibitory fibrotic
      scarring, promoted regrowth of injured raphespinal fibers and improved walking
      function after mid-thoracic spinal cord contusion injury in adult rats. These
      results confirm that systemic administration of epothilones is a valuable
      therapeutic strategy for CNS regeneration and repair after injury and provides a
      further advance for potential clinical translation.

PMID- 29223323
TI  - Olanzapine, blonanserin, and aripiprazole associated with different
      frontostriatal reward system activation in patients with schizophrenia.

PMID- 29223324
TI  - Characterization of charged polymer self-assemblies by multidetector thermal
      field-flow fractionation in aqueous mobile phases.
AB  - Charged block copolymer self-assemblies, such as charged micelles, have attracted
      much attention as versatile drug delivery systems due to their readily tunable
      characteristics such as size and surface charge. However, current column-based
      analytical techniques are not suitable to fractionate and comprehensively
      characterize charged micelles in terms of size, molar mass, chemical composition
      and morphology. Multidetector thermal field-flow fractionation (ThFFF) is shown
      to be a unique characterization platform that can be used to characterize charged
      micelles in terms of size, molar mass, chemical composition and morphology in
      aqueous mobile phases with various ionic strengths and pH. This is demonstrated
      by the characterization of poly(methacrylic acid)-b-poly(methyl methacrylate)
      self-assemblies in high pH buffers as well as the characterization of cationic
      poly(2-vinyl pyridine)-b-polystyrene and poly(4-vinyl pyridine)-b-polystyrene
      self-assemblies in low pH buffers. Moreover, it is shown that ThFFF is capable of
      separating charged micelles according to the corona composition. These
      investigations prove convincingly that ThFFF is broadly applicable to the
      comprehensive characterization of amphiphilic self-assemblies even when aqueous
      mobile phases are used.

PMID- 29223325
TI  - Cochrane Qualitative and Implementation Methods Group guidance series-paper 4:
      methods for assessing evidence on intervention implementation.
AB  - OBJECTIVES: This article provides reviewers with guidance on methods for
      identifying and processing evidence to understand intervention implementation.
      STUDY DESIGN AND SETTING: Strategies, tools, and methods are applied to the
      systematic review process to illustrate how process and implementation can be
      addressed using quantitative, qualitative, and other sources of evidence (i.e.,
      descriptive textual and nonempirical). RESULTS: Reviewers can take steps to
      navigate the heterogeneity and level of uncertainty present in the concepts,
      measures, and methods used to assess implementation. Activities can be undertaken
      in advance of a Cochrane quantitative review to develop program theory and logic
      models that situate implementation in the causal chain. Four search strategies
      are offered to retrieve process and implementation evidence. Recommendations are
      made for addressing rigor or risk of bias in process evaluation or implementation
      evidence. Strategies are recommended for locating and extracting data from
      primary studies. The basic logic is presented to assist reviewers to make initial
      review-level judgments about implementation failure and theory failure.
      CONCLUSION: Although strategies, tools, and methods can assist reviewers to
      address process and implementation using quantitative, qualitative, and other
      forms of evidence, few exemplar reviews exist. There is a need for further
      methodological development and trialing of proposed approaches.

PMID- 29223326
TI  - Effects of Perceived Discrimination and Trust on Breast Cancer Screening among
      Korean American Women.
AB  - OBJECTIVE: Korean American (KA) women continue to have lower breast cancer
      screening rates than other racial groups. Perceived discrimination and trust have
      been associated with breast cancer screening adherence, but little is known about
      the associations in KA women. METHODS: Surveys were completed by 196 KA women in
      the Chicago metropolitan area. Multiple and Firth logistic regression analyses
      were performed to identify factors (perceived discrimination, trust,
      acculturation, cultural beliefs, health care access) influencing breast cancer
      screening adherence (mammogram). In addition, SPSS macro PROCESS was used to
      examine the mediating role of trust between perceived discrimination and breast
      cancer screening adherence. RESULTS: Ninety-three percent of the women surveyed
      had health insurance and 54% reported having a mammogram in the past 2 years.
      Predictors of having a mammogram were knowing where to go for a mammogram, having
      a regular doctor or usual place for health care, greater trust in health care
      providers, and lower distrust in the health care system. Perceived discrimination
      had an indirect effect on breast cancer screening through trust. CONCLUSIONS: The
      breast cancer screening rate among KA women is low. Perceived discrimination in
      health care, trust in health care providers, and distrust in the health care
      system directly or indirectly influenced breast cancer screening adherence in KA
      women. Trust is a factor that can be strengthened with educational interventions.

PMID- 29223327
TI  - Restoration of motor function after operative reconstruction of the acutely
      transected spinal cord in the canine model.
AB  - BACKGROUND: Cephalosomatic anastomosis or what has been called a "head
      transplantation" requires full reconnection of the respective transected ends of
      the spinal cords. The GEMINI spinal cord fusion protocol has been developed for
      this reason. Here, we report the first randomized, controlled study of the GEMINI
      protocol in large animals. METHODS: We conducted a randomized, controlled study
      of a complete transection of the spinal cord at the level of T10 in dogs at
      Harbin Medical University, Harbin, China. These dogs were followed for up to 8
      weeks postoperatively by assessments of recovery of motor function, somato
      sensory evoked potentials, and diffusion tensor imaging using magnetic resonance
      imaging. RESULTS: A total of 12 dogs were subjected to operative exposure of the
      dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy
      followed by a very sharp, controlled, full-thickness, complete transection of the
      spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to
      the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was
      applied to the site of transection in the remaining 5 control dogs. Dogs were
      selected randomly to receive polyethylene glycol or saline. All polyethylene
      glycol-treated dogs reacquired a substantial amount of motor function versus none
      in controls over these first 2 months as assessed on the 20-point (0-19), canine,
      Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials
      confirmed restoration of electrical conduction cranially across the site of
      spinal cord transection which improved over time. Diffusion tensor imaging, a
      magnetic resonance permutation that assesses the integrity of nerve fibers and
      cells, showed restitution of the transected spinal cord with polyethylene glycol
      treatment (at-injury level difference: P<.02). CONCLUSION: A sharply and fully
      transected spinal cord at the level of T10 can be reconstructed with restoration
      of many aspects of electrical continuity in large animals following the GEMINI
      spinal cord fusion protocol, with objective evidence of motor recovery and of
      electrical continuity across the site of transection, opening the way to the
      first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.).

PMID- 29223328
TI  - Shared decision-making during surgical consultation for gallstones at a safety
      net hospital.
AB  - BACKGROUND: Understanding patient perspectives regarding shared decision-making
      is crucial to providing informed, patient-centered care. Little is known about
      perceptions of vulnerable patients regarding shared decision-making during
      surgical consultation. The purpose of this study was to evaluate whether a
      validated tool reflects perceptions of shared decision-making accurately among
      patients seeking surgical consultation for gallstones at a safety-net hospital.
      METHODS: A mixed methods study was conducted in a sample of adult patients with
      gallstones evaluated at a safety-net surgery clinic between May to July 2016.
      Semi-structured interviews were conducted after their initial surgical
      consultation and analyzed for emerging themes. Patients were administered the
      Shared Decision-Making Questionnaire and Autonomy Preference Scale. Univariate
      analyses were performed to identify factors associated with shared decision
      making and to compare the results of the surveys to those of the interviews.
      RESULTS: The majority of patients (N = 30) were female (90%), Hispanic (80%),
      Spanish-speaking (70%), and middle-aged (45.7 +/- 16 years). The proportion of
      patients who perceived shared decision-making was greater in the Shared Decision
      Making Questionnaire versus the interviews (83% vs 27%, P < .01). Age, sex,
      race/ethnicity, primary language, diagnosis, Autonomy Preference Scale score, and
      decision for operation was not associated with shared decision-making.
      Contributory factors to this discordance include patient unfamiliarity with
      shared decision-making, deference to surgeon authority, lack of discussion about
      different treatments, and confusion between aligned versus shared decisions.
      CONCLUSION: Available questionnaires may overestimate shared decision-making in
      vulnerable patients suggesting the need for alternative or modifications to
      existing methods. Furthermore, such metrics should be assessed for correlation
      with patient-reported outcomes, such as satisfaction with decisions and health
      status.

PMID- 29223329
TI  - The impact of psychosis on brain anatomy in bipolar disorder: A structural MRI
      study.
AB  - BACKGROUND: Bipolar disorder (BD) is a major psychiatric illness characterized by
      heterogeneous symptoms including psychotic features. Up until now, neuroimaging
      studies investigating cerebral morphology in patients with BD have underestimated
      the potential impact of psychosis on brain anatomy in BD patients. In this
      regard, psychotic and non-psychotic BD may represent biologically different
      subtypes of the disorder, being possibly associated with specific cerebral
      features. METHODS: In the present study, magnetic resonance imaging (MRI) at 3T
      was used to identify the neuroanatomical correlates of psychosis in an
      International sample of BD patients. A large sample of structural MRI data from
      healthy subjects (HC) and BD patients was collected across two research centers.
      Voxel based morphometry was used to compare gray matter (GM) volume among
      psychotic and non-psychotic BD patients and HC. RESULTS: We found specific
      structural alterations in the two patient groups, more extended in the psychotic
      sample. Psychotic patients showed GM volume deficits in left frontal cortex
      compared to HC, and in right temporo-parietal cortex compared to both HC and non
      psychotic patients (p < 0.001, > 100 voxels). Psychotic patients also exhibited
      enhanced age-related GM volume deficits in a set of subcortical and cortical
      regions. LIMITATIONS: The integration of multiple datasets may have affected the
      results. CONCLUSIONS: Overall, our results confirm the importance of classifying
      BD based on psychosis. The knowledge of the neuronal bases of psychotic
      symptomatology in BD can provide a more comprehensive picture of the determinants
      of BD, in the light of the continuum characteristic of major psychoses.

PMID- 29223330
TI  - Expression of a populus histone deacetylase gene 84KHDA903 in tobacco enhances
      drought tolerance.
AB  - Histone deacetylases (HDACs) play a key role in regulating plant growth,
      development and stress responses. However, functions of HDACs in woody plants are
      largely unknown. In this study, a novel gene encoding a RPD3/HDA1-type histone
      deacetylase was cloned from 84K poplar (Populus alba*Populus glandulosa) and
      designated as 84KHDA903. The 84KHDA903 encodes a protein composed of 500 amino
      acid residues, which contains a conserved HDAC domain. Transient expression of
      84KHDA903 in onion epidermal cells suggested that it was exclusively localized in
      nucleus. The 84KHDA903 exhibited different expression patterns under drought,
      salt and ABA treatments. The expression of 84KHDA903 was responsive to drought
      and ABA but not to salt. To understand the function of 84KHDA903 in stress
      responses, the 84KHDA903 gene was transformed into tobacco. The expression of
      84KHDA903 in tobacco increased the tolerance of transgenic seeds to mannitol but
      not to salt. In adult stage, the 84KHDA903-expressing tobacco exhibited drought
      tolerance and showed strong capacity to recover after drought. During the
      recovery period, the stress-responsive genes including NtDREB4, NtDREB3 and
      NtLEA5 were induced to be highly expressed in the 84KHDA903 transgenic plants in
      contrast to wild-type plants. Taken together, for the first time, we reported a
      RPD3/HDA1-type histone deacetylase from poplar, 84KHDA903, which acted as a
      positive regulator in drought stress responses.

PMID- 29223331
TI  - The NOS-like protein from the microalgae Ostreococcus tauri is a genuine and
      ultrafast NO-producing enzyme.
AB  - The exponential increase of genomes' sequencing has revealed the presence of NO
      Synthases (NOS) throughout the tree of life, uncovering an extraordinary
      diversity of genetic structure and biological functions. Although NO has been
      shown to be a crucial mediator in plant physiology, NOS sequences seem present
      solely in green algae genomes, with a first identification in the picoplankton
      species Ostreococcus tauri. There is no rationale so far to account for the
      presence of NOS in this early-diverging branch of the green lineage and its
      absence in land plants. To address the biological function of algae NOS, we
      cloned, expressed and characterized the NOS oxygenase domain from Ostreococcus
      tauri (OtNOSoxy). We launched a phylogenetic and structural analysis of algae
      NOS, and achieved a 3D model of OtNOSoxy by homology modeling. We used a
      combination of various spectroscopies to characterize the structural and
      electronic fingerprints of some OtNOSoxy reaction intermediates. The analysis of
      OtNOSoxy catalytic activity and kinetic efficiency was achieved by stoichiometric
      stopped-flow. Our results highlight the conserved and particular features of
      OtNOSoxy structure that might explain its ultrafast NO-producing capacity. This
      integrative Structure-Catalysis-Function approach could be extended to the whole
      NOS superfamily and used for predicting potential biological activity for any new
      NOS.

PMID- 29223332
TI  - A wheat MYB transcriptional repressor TaMyb1D regulates phenylpropanoid
      metabolism and enhances tolerance to drought and oxidative stresses in transgenic
      tobacco plants.
AB  - MYB transcription factors are involved in the regulation of plant development and
      response to biotic and abiotic stress. In this study, TaMyb1D, a novel subgroup 4
      gene of the R2R3-MYB subfamily, was cloned from wheat (Triticum aestivum L.).
      TaMyb1D was localized in the nucleus and functioned as a transcriptional
      repressor. The overexpression of TaMyb1D in tobacco (Nicotiana tabacum) plants
      repressed the expression of genes related to phenylpropanoid metabolism and down
      regulated the accumulation of lignin in stems and flavonoids in leaves. These
      changes affected plant development under normal conditions. The expression of
      TaMyb1D was ubiquitous and up-regulated by PEG6000 and H2O2 treatments in wheat.
      TaMyb1D-overexpressing transgenic tobacco plants exhibited higher relative water
      content and lower water loss rate during drought stress, as well as higher
      chlorophyll content in leaves during oxidative stress. The transgenic plants
      showed a lower leakage of ions as well as reduced malondialdehyde and H2O2 levels
      during conditions of drought and oxidative stresses. In addition, TaMyb1D up
      regulated the expression levels of ROS- and stress-related genes in response to
      drought stress. Therefore, the overexpression of TaMyb1D enhanced tolerance to
      drought and oxidative stresses in tobacco plants. Our study demonstrates that
      TaMyb1D functions as a negative regulator of phenylpropanoid metabolism and a
      positive regulator of plant tolerance to drought and oxidative stresses.

PMID- 29223333
TI  - Constitutive expression of Brassica juncea annexin, AnnBj2 confers salt tolerance
      and glucose and ABA insensitivity in mustard transgenic plants.
AB  - Annexins belong to a plasma membrane binding (in a calcium dependent manner),
      multi-gene family of proteins, which play ameliorating roles in biotic and
      abiotic stresses. The expression of annexin AnnBj2 of Indian mustard is tissue
      specific with higher expression in roots and under treatments with sodium
      chloride and abscisic acid (ABA) at seedling stage. The effect of constitutive
      expression of AnnBj2 in mustard was analyzed in detail. AnnBj2 OE (over
      expression) plants exhibited insensitivity to ABA, glucose and sodium chloride.
      The insensitivity/tolerance of the transgenic plants was associated with enhanced
      total chlorophylls, relative water content, proline, calcium and potassium with
      reduced thiobarbituric acid reactive substances and sodium ion accumulation. The
      altered ABA insensitivity of AnnBj2 OE lines is linked to downregulation of ABI4
      and ABI5 transcription factors and upregulation of ABA catabolic gene CYP707A2.
      Furthermore, we found that overexpression of AnnBj2 upregulated the expression of
      ABA-dependent RAB18 and ABA-independent DREB2B stress marker genes suggesting
      that the tolerance phenotype exhibited by AnnBj2 OE lines is probably controlled
      by both ABA-dependent and -independent mechanisms.

PMID- 29223334
TI  - Expression of phytoglobin affects nitric oxide metabolism and energy state of
      barley plants exposed to anoxia.
AB  - Class 1 plant hemoglobins (phytoglobins) are upregulated during low-oxygen stress
      and participate in metabolism and cell signaling via modulation of the levels of
      nitric oxide (NO). We studied the effects of overexpression and knockdown of the
      class 1 phytoglobin gene in barley (Hordeum vulgare L.) under low-oxygen stress.
      The overexpression of phytoglobin reduced the amount of NO released, while
      knockdown significantly stimulated NO emission. It has previously been shown that
      NO inhibits aconitase activity, so decreased aconitase activity in knockdown
      plants acts as a biomarker for high internal NO levels. The overexpression of
      phytoglobin corresponded to higher ATP/ADP ratios, pyrophosphate levels and
      aconitase activity under anoxia, while knockdown of phytoglobin resulted in the
      increased level of protein nitrosylation, elevation of alcohol dehydrogenase and
      nitrosoglutathione reductase activities. The overexpressing plants showed various
      signs of stunted growth under normoxia, but were the only type to germinate and
      survive under hypoxia. The results show that overexpression of phytoglobin
      protects plant cells via NO scavenging and improves their low-oxygen stress
      survival. However, it may not be useful for cereal crop improvement since it
      comes with a significant interference with normoxic NO signalling pathways.

PMID- 29223335
TI  - Genome-wide identification of glycosyltransferases converting phloretin to
      phloridzin in Malus species.
AB  - Phloridzin (phloretin 2'-O-glucoside) is the most abundant phenolic compound in
      Malus species, accounting for up to 18% of the dry weight in leaves.
      Glycosylation of phloretin at the 2' position is the last and key step in
      phloridzin biosynthesis. It is catalyzed by a uridine diphosphate (UDP)
      glucose:phloretin 2'-O-glucosyltransferase (P2'GT), which directly determines the
      concentration of phloridzin. However, this process is poorly understood. We
      conducted a large-scale investigation of phloridzin accumulations in leaves from
      64 Malus species and cultivars. To identify the responsible P2'GT, we performed a
      genome-wide analysis of the expression patterns of UDP-dependent
      glycosyltransferase genes (UGTs). Two candidates were screened preliminarily in
      Malus spp. cv. Adams (North American Begonia). Results from further qRT-PCR
      analyses of the genotypes showed a divergence in phloridzin production. Our
      assays of enzyme activity also suggested that MdUGT88F4 and MdUGT88F1 regulate
      the conversion of phloretin to phloridzin in Malus plants. Finally, when they
      were silenced in 'GL-3' ('Royal Gala'), the concentrations of phloridzin and
      phloretin (and trilobatin) were significantly reduced and increased,
      respectively.

PMID- 29223336
TI  - Association of candidate genes with heading date in a diverse Dactylis glomerata
      population.
AB  - Flowering occurs in response to cues from both temperature and photoperiod
      elicitors in cool-season, long-day forage grasses, and genes involved in sensing
      the elicitors and inducing downstream flowering responses have been associated
      with heading date and flowering time in perennial forage grasses as well as
      cereal grasses. In this study we test for association between orchardgrass
      (Dactylis glomerata L.) heading date and polymorphisms in the CONSTANS (DgCO1),
      FLOWERING TIME (DgFT1), a VRN1 like MADS-box (DgMADS), and PHOTOPERIOD (DgPPD1
      like) containing genes. A diverse population of 150 genotypes was measured for
      heading date across three years, genotyped, and candidate genes sequenced.
      Although pairwise population kinship values were generally low, the genotypes fit
      into a two-group structure model. Linkage disequilibrium decayed rapidly,
      reaching r2 levels below 0.2 within the 500bp of each gene. SNPs significantly
      associated with heading date were detected in equal-dose and tetraploid dosage
      models. The DgCO1 gene had the most significant polymorphisms and those with the
      largest effects, while DgMADS had several significant polymorphisms in its first
      intron with smaller effects. These polymorphisms can be used for further
      validation, selection, and development of breeding lines of orchardgrass.

PMID- 29223337
TI  - An ERF transcription factor from Tamarix hispida, ThCRF1, can adjust osmotic
      potential and reactive oxygen species scavenging capability to improve salt
      tolerance.
AB  - Ethylene-Responsive Factors (ERFs) are plant-specific transcription factors (TFs)
      involved in multiple biological processes, especially in abiotic stress
      tolerance. However, the ERFs from woody halophytes that are involved in salt
      stress have been little studied. In the present investigation, we characterized a
      subfamily member of ERF TFs from Tamarix hispida, ThCRF1, which responds to salt
      stress. ThCRF1 is a nuclear protein that binds to the motifs including TTG, DRE
      and GCC-box. Transient transformation was performed to generate T. hispida
      overexpressing ThCRF1 and RNA interference (RNAi)-silenced ThCRF1 to analyze its
      function using gain- and loss-of-function methods. Overexpression of ThCRF1 in T.
      hispida significantly improved tolerance to salt-shock-induced stress; by
      contrast, RNAi-silence of ThCRF1 significantly decreased tolerance to salt-shock
      induced stress. Further experiments showed that ThCRF1 induces the expression of
      genes including those encoding pyrroline-5-carboxylate synthetase (P5CS),
      trehalose-6-phosphate synthase (TPS), trehalose-6-phosphate phosphatase (TPP),
      superoxide dismutase (SOD) and peroxidase (POD), which lead to enhanced proline
      and trehalose levels and increased SOD and POD activities. These results were
      further confirmed by studying transgenic Arabidopsis plants overexpressing
      ThCRF1. Therefore, the results suggested that ThCRF1 improves tolerance to salt
      shock-induced stress by enhancing trehalose and proline biosynthesis to adjust
      the osmotic potential, and by improving SOD and POD activities to increase
      reactive oxygen species scavenging capability.

PMID- 29223338
TI  - Molecular cloning and expression analysis of Aquaporin genes in pearl millet
      [Pennisetum glaucum (L) R. Br.] genotypes contrasting in their transpiration
      response to high vapour pressure deficits.
AB  - Pearl millet is a crop of the semi-arid tropics having high degree of genetic
      diversity and variable tolerance to drought stress. To investigate drought
      tolerance mechanism that possibly accounts for differences in drought tolerance,
      four recombinant inbred lines from a high resolution cross (HRC) were selected
      for variability in their transpiration rate (Tr) response to vapour pressure
      deficit (VPD) conditions. The differential Tr response of the genotypes to
      increased VPD conditions was used to classify the genotypes as sensitive or
      insensitive to high VPD. Aquaporin (AQP) genes PgPIP1;1, PgPIP1;2, PgPIP2;1,
      PgPIP2;3, PgPIP2;6, PgTIP1;1 and PgTIP2;2 were cloned. Phylogenetic analysis
      revealed that the cloned PgAQPs were evolutionarily closer to maize AQPs than to
      rice. PgAQP genes, including PgPIP1;1 and PgPIP2;6 in root tissue showed a
      significant expression pattern with higher expression in VPD-insensitive
      genotypes than VPD-sensitive genotypes under low VPD conditions (1.2kPa) i.e when
      there is no high evaporative demand from the atmosphere. PgAQP genes (PgPIP2;1 in
      leaf and root tissues; PgPIP1;2 and PgTIP2;2 in leaf and PgPIP2;6 in root)
      followed a diurnal rhythm in leaves and roots that have either higher or lower
      expression levels at different time intervals. Under high VPD conditions
      (4.21kPa), PgPIP2;3 showed higher transcript abundance in VPD-insensitive
      genotypes, and PgPIP2;1 in VPD-sensitive genotypes, while rest of the PgAQPs
      showed differential expression. Our current hypothesis is that these differences
      in the expression of AQP genes under different VPDs suggests a role of the AQPs
      in tuning the water transport pathways with variation between genotypes.

PMID- 29223339
TI  - MicroRNA396a-5p and -3p induce tomato disease susceptibility by suppressing
      target genes and upregulating salicylic acid.
AB  - Plants have evolved a variety of mechanisms to perceive and resist the assault of
      pathogens. The biotrophs, necrotrophs and hemibiotrophs are types of plant
      pathogens that activate diverse salicylic acid (SA) and jasmonic acid (JA)
      signaling pathways. In this study we showed that the expressions of miR396a-5p
      and -3p in Solanum lycopersicum (S. lycopersicum) were both down-regulated after
      infection by hemibiotroph Phytophthora infestans (P. infestans) and necrotroph
      Botrytis cinerea (B. cinerea) infection. Overexpression of miR396a-5p and -3p in
      transgenic tomato enhanced the susceptibility of S. lycopersicum to P. infestans
      and B. cinerea infection and the tendency to produce reactive oxygen species
      (ROS) under pathogen-related biotic stress. Additionally, miR396a regulated
      growth-regulating factor1 (GRF1), salicylic acid carboxyl methyltransferase
      (SAMT), glycosyl hydrolases (GH) and nucleotide-binding site-leucine-rich repeat
      (NBS-LRR) and down-regulated their levels. This ultimately led to inhibition of
      the expression of pathogenesis-related 1 (PR1), TGA transcription factors1 and 2
      (TGA1 and TGA2) and JA-dependent proteinase inhibitors I and II (PI I and II),
      but enhanced the endogenous SA content and nonexpressor of pathogenesis-related
      genes 1 (NPR1) expression. Taken together, our results showed that negative
      regulation of target genes and their downstream genes expressions by miR396a-5p
      and -3p are critical for tomato abiotic stresses via affecting SA or JA signaling
      pathways.

PMID- 29223340
TI  - Silencing of histone deacetylase SlHDT3 delays fruit ripening and suppresses
      carotenoid accumulation in tomato.
AB  - The acetylation levels of histones on lysine residues are regulated by histone
      acetyltransferases and histone deacetylases, which play an important but
      understudied role in the control of gene expression in plants. There is an
      increasing research focus on histone deacetylation in crops, but to date, there
      is little information regarding tomato. With the aim of characterizing the tomato
      HD2 family of histone deacetylases, an RNA interference (RNAi) expression vector
      of SlHDT3 was constructed and transformed into tomato plants. The time of fruit
      ripening was delayed and the shelf life of the fruit was prolonged in SlHDT3 RNAi
      lines. The accumulation of carotenoid was decreased by altering of the carotenoid
      pathway flux. Ethylene content was also reduced and expression of ethylene
      biosynthetic genes (ACS2, ACS4 and ACO1, ACO3) and ripening-associated genes
      (RIN, E4, E8, PG, Pti4 and LOXB) was significantly down-regulated in SlHDT3 RNAi
      lines. The expression of genes involved in fruit cell wall metabolism (HEX, MAN,
      TBG4, XTH5 and XYL) was inhibited compared with wild type. These results indicate
      that SlHDT3 functions as a positive regulator of fruit ripening by affecting
      ethylene synthesis and carotenoid accumulation and that SlHDT3 lies upstream of
      SlMADS-RIN in the fruit ripening regulatory network.

PMID- 29223341
TI  - Genetic resistance against viruses in Phaseolus vulgaris L.: State of the art and
      future prospects.
AB  - Viruses are obligate parasites that replicate intracellularly in many living
      organisms, including plants. Consequently, no chemicals are available that target
      only the virus without impacting host cells or vector organisms. The use of
      natural resistant varieties appears as the most reliable control strategy and
      remains the best and cheapest option in managing virus diseases, especially in
      the current ecological context of preserving biodiversity and environment in
      which the use of phytosanitary products becomes limited. Common bean is a grain
      legume cultivated mainly in Africa and Central-South America. Virus diseases of
      common bean have been extensively studied both by breeders to identify natural
      resistance genes in existing germplasms and by pathologists to understand the
      molecular bases of plant-virus interactions. Here we present a critical review in
      which we synthesize previous and recent information concerning 1) main viruses
      causing diseases in common bean, 2) genetic resistance to viruses in common bean,
      3) the different resistance phenotypes observed and more particularly the effect
      of temperature, 4) the molecular bases of resistance genes to viruses in common
      bean, and 5) future prospects using transgenic-engineered resistant lines.

PMID- 29223342
TI  - Enhanced resistance to rice blast and sheath blight in rice (oryza sativa L.) by
      expressing the oxalate decarboxylase protein Bacisubin from Bacillus subtilis.
AB  - Oxalate decarboxylase (OxDC), catalyzing the degradation of oxalic acid, is
      widely distributed in varieties of organisms. In this study, an oxalate
      decarboxylase gene from Bacillus subtilis strain BS-916, Bacisubin, was
      transformed into rice variety Nipponbare to generate transgenic rice with
      increased OxDC activity. Pathogenicity test revealed that the transgenic rice
      showed enhanced resistance to rice blast and sheath blight. Further RNA-seq
      analysis between Nipponbare WT (wild type) and transgenic rice identified 1764
      DEGs (Differentially expressed genes) including 723 up-regulated unigenes and
      1041 down-regulated unigenes. Five GO terms including single-organism process and
      oxidation-reduction process were significantly enriched in the up-regulated
      genes. Interestingly, five genes encoding glutaredoxin and one gene encoding MADS
      box were up- and down-regulated in the transgenic rice, respectively.
      Collectively, our study advances the understanding of OxDC in resistance to rice
      disease and its possible mechanisms. Our results also suggest that OxDC would be
      an effective antifungal protein preventing fungal infection in transgenic rice.

PMID- 29223344
TI  - Native vascular related NAC transcription factors are efficient regulator of
      multiple classes of secondary wall associated genes in banana.
AB  - Secondary-wall deposition in xylem vessel elements is regulated by vascular
      related NAC transcription factors (VNDs). We show that three banana VNDs
      (MusaVND1, MusaVND2 and MusaVND3) directly regulate multiple secondary-wall
      associated genes by binding to their 5'-upstream regulatory region. Transgenic
      banana harboring either PMusaVND1:GUS, PMusaVND2:GUS or PMusaVND3:GUS showed
      specific GUS staining in lignified tissues. MusaVND1, MusaVND2 and MusaVND3
      encodes transcriptional-activators as its C-terminal region drive expression of
      reporter genes in vivo in yeast. Purified MusaVND1, MusaVND2 and MusaVND3
      proteins in gel shift assay bind to 19-bp secondary-wall NAC binding element
      (SNBE) while it fails to bind mutated SNBE. Putative SNBE sites in the 5'
      upstream regulatory region of important secondary-wall associated genes related
      to programmed cell death (XCP1), cell-wall modification (IRX1/CesA8,
      IRX3/CesA7,IRX5/CesA4, IRX8, IRX10 and IRX12) and transcriptional regulation
      (MYB52, MYB48/59, MYB85, MYB58/72, MYB46, and MYB83) in banana was identified and
      mobility of these regulatory regions got retarded by MusaVND1, MusaVND2 and
      MusaVND3. Transcript level of these important secondary wall associated genes
      were elevated in transgenic banana overexpressing either MusaVND1, MusaVND2 or
      MusaVND3. Present study suggested promoters with prospective utilization in wall
      modification in banana (a potential biofuel crop) and suggest a complex
      transcriptional regulation of secondary wall deposition in plants.

PMID- 29223343
TI  - Biotic factors that induce the tomato Ve1 R-gene.
AB  - In tomato, Verticillium resistance is determined by the Ve gene locus encoding
      two leucine-rich repeat-receptor-like proteins (Ve1, Ve2). The resistance
      function usually is attributed to Ve1 alone, with two known alleles: Ve1,
      encoding a resistance protein, and ve1, with a premature stop codon encoding a
      truncated product. We have examined further Ve-gene expression in resistant and
      susceptible near-isolines of Verticillium-infected Craigella tomatoes, using both
      quantitative RT-PCR and an alternative RFLP assay. Ve1 is induced differentially
      in resistant and susceptible plants, while Ve2 is constitutively expressed
      throughout disease development. Contrary to their putative role in Verticillium
      resistance, these profiles were observed even with compatible Verticillium
      interactions, some bacterial pathogens, and transgenic tomato plants expressing
      the fungal Ave1 effector. This suggests broader roles in disease and/or stress.
      To determine the contribution of plant hormones, abscisic acid, methyl jasmonate,
      naphthaleneacetic acid or salicylic acid were infused independently via the
      tomato root and effects on Ve1 induction were confirmed using biosynthesis
      mutants. While all the hormones modulated Ve1-gene induction, abscisic acid and
      salicylic acid were not required while jasmonic acid appears to play a more
      direct role.

PMID- 29223345
TI  - Synergy between root hydrotropic response and root biomass in maize (Zea mays L.)
      enhances drought avoidance.
AB  - Roots of higher plants change their growth direction in response to moisture,
      avoiding drought and gaining maximum advantage for development. This response is
      termed hydrotropism. There have been few studies of root hydrotropism in grasses,
      particularly in maize. Our goal was to test whether an enhanced hydrotropic
      response of maize roots correlates with a better adaptation to drought and
      partial/lateral irrigation in field studies. We developed a laboratory bioassay
      for testing hydrotropic response in primary roots of 47 maize elite DTMA (Drought
      Tolerant Maize for Africa) hybrids. After phenotyping these hybrids in the
      laboratory, selected lines were tested in the field. Three robust and three weak
      hybrids were evaluated employing three irrigation procedures: normal irrigation,
      partial lateral irrigation and drought. Hybrids with a robust hydrotropic
      response showed growth and developmental patterns, under drought and partial
      lateral irrigation, that differed from weak hydrotropic responders. A correlation
      between root crown biomass and grain yield in hybrids with robust hydrotropic
      response was detected. Hybrids with robust hydrotropic response showed earlier
      female flowering whereas several root system traits, such as projected root area,
      median width, maximum width, skeleton width, skeleton nodes, average tip
      diameter, rooting depth skeleton, thinner aboveground crown roots, as well as
      stem diameter, were considerably higher than in weak hydrotropic responders in
      the three irrigation procedures utilized. These results demonstrate the benefit
      of intensive phenotyping of hydrotropism in primary roots since maize plants that
      display a robust hydrotropic response grew better under drought and partial
      lateral irrigation, indicating that a selection for robust hydrotropism might be
      a promising breeding strategy to improve drought avoidance in maize.

PMID- 29223346
TI  - [Combination of left atrial myxoma and retrocardiac liposarcoma with right atrial
      infiltration].

PMID- 29223347
TI  - [A predictive bacterial infection score according to eosinophil level: An
      observational study].
AB  - INTRODUCTION: Several studies have shown that eosinopenia less than 0.04g/L is a
      marker of bacterial infection in the presence of unexplained inflammatory
      syndrome. The aim of our study was to test this hypothesis and to propose a
      predictive score for bacterial infection (score CIBLE, C reactive protein,
      bacterial infections, levels of leucocytes and eosinophils). PATIENTS AND
      METHODS: This was a single-center observational study of patients admitted to an
      internal medicine department in the year 2015 and presenting with an inflammatory
      biological syndrome. Patients were divided into 2 groups: bacterial infections
      (group 1) and nonbacterial inflammatory diseases (group 2). RESULTS: One hundred
      and ninety patients were included: 92 men (48.4 %) and 98 women (51.6 %). Mean
      age was 73.5+/-18.2 years [19-104]. Group 1 consisted of 124 patients (65.2 %)
      and group 2 of 66 patients (34.8 %). ROC analysis confirmed a cut-off level for
      eosinophils count at 0.04g/L as discriminant to predict bacterial infection. In a
      multivariate analysis, the eosinophil/neutrophil ratio, a history of COPD, the C
      reactive protein concentration, patient age and initial temperature were the most
      significant variables. They were used to build the CIBLE score. For a score
      higher than or equal to 87, the probability of a bacterial infection is at least
      70 %. CONCLUSION: The CIBLE score appears to be a relevant and inexpensive tool
      to establish a probability for bacterial infection.

PMID- 29223348
TI  - Distinctive binding properties of the negative allosteric modulator,
      [3H]SB269,652, at recombinant dopamine D3 receptors.
AB  - Recently, employing radioligand displacement and functional coupling studies, we
      demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4
      tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts
      in an atypical manner with dopamine D3 receptor displaying a unique profile
      reminiscent of a negative allosteric ligand. Here, we characterized the binding
      of radiolabelled [3H]SB269,652 to human dopamine D3 receptor stably expressed in
      Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD
      value of ~ 1nM. Consistent with high selectivity for human dopamine D3 receptor,
      [3H]SB269,652 binding was undetectable in cells expressing human dopamine D1, D2L
      or D4 receptors and absent in synaptosomes from dopamine D3 receptor knockout vs.
      wild-type mice. In contrast to saturation binding experiments, the dissociation
      kinetics of [3H]SB269,652 from human dopamine D3 receptors initiated with an
      excess of unlabelled ligand were best fitted by a bi-exponential binding model.
      Supporting the kinetic data, competition experiments with haloperidol, S33084 (a
      dopamine D3 receptor antagonist) or dopamine, were best described by a two-site
      model. In co-transfection experiments binding of SB269,652 to dopamine D3
      receptor was able to influence the functional coupling of dopamine D2 receptor,
      supporting the notion that SB269,652 is a negative allosteric modulator across
      receptor dimers. However, because SB269,652 decreases the rate of [3H]nemonapride
      dissociation, the present data suggest that SB269,652 behaves as a bitopic
      antagonist at unoccupied dopamine D3 receptor, binding simultaneously to both
      orthosteric and allosteric sites, and as a pure negative allosteric modulator
      when receptors are occupied and it can solely bind to the allosteric site.

PMID- 29223349
TI  - The Effect of Cerebellar Transcranial Direct Current Stimulation on A Throwing
      Task Depends on Individual Level of Task Performance.
AB  - The effect of cerebellar transcranial direct current stimulation (tDCS) on motor
      performance remains controversial. Some studies suggest that the effect of tDCS
      depends upon task-difficulty and individual level of task performance. Here, we
      investigated whether the effect of cerebellar tDCS on the motor performance
      depends upon the individual's level of performance. Twenty-four naive
      participants practiced dart throwing while receiving a 2-mA cerebellar tDCS for
      20 min under three stimulus conditions (anodal-, cathodal-, and sham-tDCS) on
      separate days with a double-blind, counter-balanced cross-over design. Task
      performance was assessed by measuring the distance between the center of the
      bull's eye and the dart's position. Although task performance tended to improve
      throughout the practice under all stimulus conditions, improvement within a given
      day was not significant as compared to the first no-stimulus block. In addition,
      improvement did not differ among stimulation conditions. However, the magnitude
      of improvement was associated with an individual's level of task performance only
      under cathodal tDCS condition (p < 0.05). This resulted in a significant
      performance improvement only for the sub-group of participants with lower
      performance levels as compared to that with sham-tDCS (p < 0.05). These findings
      suggest that the facilitation effect of cerebellar cathodal tDCS on motor skill
      learning of complex whole-body movements depends on the level of an individual's
      task performance. Thus, cerebellar tDCS would facilitate learning of a complex
      motor skill task only in a subset of individuals.

PMID- 29223350
TI  - alpha6 and beta1 Integrin Heterodimer Mediates Schwann Cell Interactions with
      Axons and Facilitates Axonal Regeneration after Peripheral Nerve Injury.
AB  - Several isoforms of integrin subunits are expressed in Schwann cells and mediate
      Schwann cell interactions with axons. Here, we identify alpha6 and beta1
      integrins as heterodimeric proteins expressed in Schwann cells and define their
      functions in axonal regeneration. alpha6 and beta1 integrins are induced in
      Schwann cells in the sciatic nerve after a crush injury, and the blocking of
      integrin activity by siRNA expression and by treatment with anti-integrin
      antibodies attenuates Schwann cell contact with cultured neurons and decreases
      neurite outgrowth. After nerve transection, the levels of alpha6 and beta1
      integrins in the distal nerve stump are lower than those in the corresponding
      nerve area after a crush injury. Schwann cells prepared from the distal nerves 7
      days after transection are less supportive of neurite outgrowth in co-cultured
      neurons than those prepared from the nerves 7 days after a crush injury. When the
      transected nerves are reconnected after a delay of 1 to 2 weeks, the induced
      levels of alpha6 and beta1 integrins in the reconnected distal nerves are
      significantly reduced compared to those in the nerves after a crush injury. These
      changes correlate with retarded axonal regeneration in animals that have
      experienced nerve transections and delayed coaptation, which implies an
      attenuated Schwann cell capacity to support axonal regeneration due to delayed
      Schwann cell contact with axons. The present data suggest that alpha6 and beta1
      integrins induced in Schwann cells after nerve injury may play a role in
      mediating Schwann cell interactions with axons and promote axonal regeneration.

PMID- 29223351
TI  - CK2alpha promotes advanced glycation end products-induced expressions of
      fibronectin and intercellular adhesion molecule-1 via activating MRTF-A in
      glomerular mesangial cells.
AB  - Advanced glycation end products' (AGEs) modification of extracellular matrix
      proteins induces crosslinking, which results in thickening of the basement
      membrane and activating several intracellular signaling cascades, eventually
      promoting the pathological progression of diabetic nephropathy (DN). We have
      previously confirmed that casein kinase 2alpha (CK2alpha) activates the nuclear
      factor of kappaB (NF-kappaB) signaling pathway to enhance high glucose-induced
      expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in
      glomerular mesangial cells (GMCs). However, to date, the mechanism by which
      CK2alpha regulates diabetic renal fibrosis is not fully understood. In view of
      the regulation of inflammation and fibrosis by myocardin-related transcription
      factor A (MRTF-A), we are highly concerned whether CK2alpha promotes AGEs-induced
      expressions of FN and ICAM-1 in glomerular mesangial cells via activation of MRTF
      A, thus affecting the pathogenesis of DN. We found that CK2alpha and MRTF-A
      proteins were overexpressed in AGEs-induced diabetic kidneys. Inhibition of
      CK2alpha kinase activity or knockdown of CK2alpha protein expression suppressed
      the upregulation of FN and ICAM-1 expressions in GMCs induced by AGEs. MRTF-A
      knockdown compromised the expressions of FN and ICAM-1 in GMCs induced by AGEs.
      Moreover, inhibition of CK2alpha kinase activity or knockdown of CK2alpha protein
      expression restrained the protein expression and nuclear aggregation of MRTF-A.
      CK2alpha interacted with MRTF-A. Furthermore, knockdown of MRTF-A while
      overexpression of CK2alpha blocked the upregulation effect of CK2alpha on the
      protein expressions of FN and ICAM-1. These findings suggest that CK2alpha
      promotes diabetic renal fibrosis via activation of MRTF-A and upregulation of
      inflammatory genes.

PMID- 29223353
TI  - Editor's Choice - Late Open Surgical Conversion after Endovascular Abdominal
      Aortic Aneurysm Repair.
AB  - INTRODUCTION: Late open surgical conversion following endovascular aneurysm
      repair (EVAR) may occur more frequently after performing EVAR in anatomy outside
      the instructions for use (IFU). This study reviews predictors and outcomes of
      late open surgical conversion for failed EVAR. METHODS: This retrospective cohort
      study reviewed all EVARs performed at the Ottawa Hospital between January 1999
      and May 2015. Open surgical conversions >1 month post EVAR were identified.
      Variables analysed included indication for conversion, pre-intervention AAA
      anatomy, endovascular device and configuration, operative technique, re
      interventions, complications, and death. RESULTS: Of 1060 consecutive EVARs
      performed, 16 required late open surgical conversion. Endografts implanted were
      Medtronic Talent (n = 8, 50.0%), Medtronic Endurant (n = 3, 18.8%), Cook Zenith
      (n = 4, 25.0%), and Terumo Anaconda (n = 1, 6.2%). Eleven grafts were bifurcated
      (68.8%), five were aorto-uni-iliac (31.2%). The median time to open surgical
      conversion was 3.1 (IQR 1.0-5.2) years. There was no significant difference in
      pre-EVAR rupture status (1.4% elective, 2.1% ruptured, p = .54). Indications for
      conversion included: Type 1 endoleak with sac expansion (n = 4, 25.0%), Type 2
      endoleak with expansion (n = 2, 12.5%), migration (n = 3, 18.8%), sac expansion
      without endoleak (n = 2, 12.5%), graft infection (n = 3, 18.8%), rupture (n = 2,
      12.5%). Nine patients (56.2%) underwent stent graft explantation with in situ
      surgical graft reconstruction, seven had endograft preserving open surgical
      intervention. The 30 day mortality was 18.8% (n = 3, all of whom having had
      endograft preservation). Ten patients (62.5%) suffered major in hospital
      complications. One patient (6.5%) required post-conversion major surgical re
      intervention. IFU adherence during initial EVAR was 43.8%, versus 79.0% (p < .01)
      among uncomplicated EVARs. CONCLUSIONS: Open surgical conversion following EVAR
      results in significant morbidity and mortality. IFU adherence of EVARs later
      requiring open surgical conversion is markedly low. More data are required to
      elucidate the impact of increasing liberalisation of EVAR outside of IFU.

PMID- 29223354
TI  - Double Banana Technique: A Fruity Solution for Treating Iliac Aneurysms After
      Aortic Surgery.

PMID- 29223352
TI  - ATP-binding cassette transporter-2 (ABCA2) as a therapeutic target.
AB  - The ATP binding cassette transporter ABCA2 is primarily an endolysosomal membrane
      protein that demonstrates pleiotropic functionalities, coalescing around the
      maintenance of homeostasis of sterols, sphingolipids and cholesterol. It is most
      highly expressed in brain tissue and ABCA2 knockout mice express neurological
      defects consistent with aberrant myelination. Increased expression of the
      transporter has been linked with resistance to cancer drugs, particularly those
      possessing a steroid backbone and gene expression (in concert with other genes
      involved in cholesterol metabolism) was found to be regulated by sterols.
      Moreover, in macrophages ABCA2 is influenced by sterols and has a role in
      regulating cholesterol sequestration, potentially important in cardiovascular
      disease. Accumulating data indicate the critical importance of ABCA2 in mediating
      movement of sphingolipids within cellular compartments and these have been
      implicated in various aspects of cholesterol trafficking. Perhaps because the
      functions of ABCA2 are linked with membrane building blocks, there are reports
      linking it with human pathologies, including, cholesterolemias and cardiovascular
      disease, Alzheimer's and cancer. The present review addresses whether there is
      now sufficient information to consider ABCA2 as a plausible therapeutic target.

PMID- 29223355
TI  - Multisession anodal transcranial direct current stimulation induces motor cortex
      plasticity enhancement and motor learning generalization in an aging population.
AB  - OBJECTIVES: The present aging study investigated the impact of a multisession
      anodal-tDCS protocol applied over the primary motor cortex (M1) during motor
      sequence learning on generalization of motor learning and plasticity-dependent
      measures of cortical excitability. METHODS: A total of 32 cognitively-intact
      aging participants performed five consecutive daily 20-min sessions of the serial
      reaction time task (SRTT) concomitant with either anodal (n = 16) or sham (n =
      16) tDCS over M1. Before and after the intervention, all participants performed
      the Purdue Pegboard Test (PPT) and Transcranial Magnetic Stimulation (TMS)
      measures of cortical excitability were collected. RESULTS: Relative to sham,
      participants assigned to the anodal-tDCS intervention revealed significantly
      greater performance gains on both the trained SRTT and the untrained PPT as well
      as a greater disinhibition of long-interval cortical inhibition (LICI).
      Generalization effects of anodal-tDCS significantly correlated with LICI
      disinhibition. CONCLUSION: Anodal-tDCS facilitates motor learning generalisation
      in an aging population through intracortical disinhibition effects. SIGNIFICANCE:
      The current findings demonstrate the potential clinical utility of a multisession
      anodal-tDCS over M1 protocol as an adjuvant to motor training in alleviating age
      associated motor function decline. This study also reveals the pertinence of
      implementing brain stimulation techniques to modulate age-associated
      intracortical inhibition changes in order to facilitate motor function gains.

PMID- 29223356
TI  - Isolation of novel microsatellite markers and their application for genetic
      diversity and parentage analyses in sika deer.
AB  - Every part of the sika deer (Cervus nippon) body is valuable traditional Chinese
      medicine. And sika deer is the most important semi-domestic medicinal animal that
      is widely bred in Jilin province northeast of China. But few studies had been
      conducted to characterize the microsatellite markers derived from sika deer. We
      firstly used IlluminaHiSeqTM2500 sequencing technology obtained 125Mbp genomic
      data of sika deer. Using microsatellite identification tool (MISA), 22,479
      microsatellites were identified. From these data, 100 potential primers were
      selected for further polymorphic validation, finally, 76 primer pairs were
      successfully amplified and 29 primer pairs were found to be obvious polymorphic
      in 8 different individuals. Using those polymorphic microsatellite markers, we
      analyzed the genetic diversity of Jilin sika deer population. The mean number of
      alleles of the 29 loci is 9.31 based on genotyping blood DNA from 96 Jilin sika
      deer; The mean expected heterozygosity and polymorphic information content (PIC)
      value of the 29 loci is 0.72 and 0.68 respectively, and among which 26 loci are
      highly polymorphic (PIC>0.50). According to the electrophoretic results and PIC
      value of these 29 loci, 10 loci with combined paternity exclusion
      probabilities>99.99% were selected to use in parentage verification for 16 sika
      deer. All the offspring of a family could be successfully assigned to their
      biological father. These microsatellite markers generated in this study could
      greatly facilitate future studies of molecular breeding in sika deer.

PMID- 29223357
TI  - Phylogenomic detection and functional prediction of genes potentially important
      for plant meiosis.
AB  - Meiosis is a specialized type of cell division necessary for sexual reproduction
      in eukaryotes. A better understanding of the cytological procedures of meiosis
      has been achieved by comprehensive cytogenetic studies in plants, while the
      genetic mechanisms regulating meiotic progression remain incompletely understood.
      The increasing accumulation of complete genome sequences and large-scale gene
      expression datasets has provided a powerful resource for phylogenomic inference
      and unsupervised identification of genes involved in plant meiosis. By
      integrating sequence homology and expression data, 164, 131, 124 and 162 genes
      potentially important for meiosis were identified in the genomes of Arabidopsis
      thaliana, Oryza sativa, Selaginella moellendorffii and Pogonatum aloides,
      respectively. The predicted genes were assigned to 45 meiotic GO terms, and their
      functions were related to different processes occurring during meiosis in various
      organisms. Most of the predicted meiotic genes underwent lineage-specific
      duplication events during plant evolution, with about 30% of the predicted genes
      retaining only a single copy in higher plant genomes. The results of this study
      provided clues to design experiments for better functional characterization of
      meiotic genes in plants, promoting the phylogenomic approach to the evolutionary
      dynamics of the plant meiotic machineries.

PMID- 29223358
TI  - Genome-wide mining of perfect microsatellites and tetranucleotide orthologous
      microsatellites estimates in six primate species.
AB  - Advancement in genome sequencing and in silico mining tools have provided new
      opportunities for comparative primate genomics of microsatellites. The SSRs
      (simple sequence repeats) numbers were not correlated with the genome size
      (Pearson, r=0.310, p=0.550), and were positively correlated with the total length
      of SSRs (Pearson, r=0.992, p=0.00). A total of 224,289 tetranucleotide
      orthologous microsatellites families and 367 single-copy orthologous SSRs loci
      were found in six primate species by homologous alignment. The inner mutation
      types of single-copy orthologous SSRs loci included the copy number variance,
      point mutation, and chromosomal translocation. The accumulated repeat times and
      average length of tetranucleotide orthologous microsatellites in Rhinopithecus
      roxellana, Papio anubis and Macaca mulatta were longer than Homo sapiens and Pan
      troglodytes, which showed the tetranucleotide orthologous SSRs loci had more
      repeat times and longer average length on the branches with earlier divergence
      time, one exception may be Microcebus murinus as a primitive monkey with a
      smallest morphology in Malagasy. Our conclusion indicated that single-copy
      tetranucleotide orthologous SSRs sequences accumulated individual mutation more
      slowly through time in H. sapiens and P. troglodytes than in R. roxellanae, P.
      anubis and M. mulatta. However, such divergence wouldn't arise uniformly in all
      branches of the primate tree. A comparison of genomic sequence assemblages would
      offer remarkable insights about comparisons and contrasts, and the evolutionary
      processes of the microsatellites involved in human and nonhuman primate species.

PMID- 29223359
TI  - In Niemann-Pick C1 mouse models, glial-only expression of the normal gene extends
      survival much further than do changes in genetic background or treatment with
      hydroxypropyl-beta-cyclodextrin.
AB  - The Npc1nmf164 allele of Npc1 provides a mouse model for Niemann-Pick disease
      type C1 (NPC1), a genetic disease known to have a widely variable phenotype. The
      transfer of the Npc1nmf164 mutation from the C57BL/6J inbred strain to the
      BALB/cJ inbred strain increased the mean lifespan from 117.8days to 153.1days,
      confirming that the severity of the NPC1 phenotype is strongly influenced by
      genetic background. The transfer of another Npc1 allele, Npc1nih, to this
      background also extended survival of the homozygotes indicating that the
      modifying effect of BALB/cJ is not limited to a single allele of Npc1. The
      increased longevity due to the BALB/cJ background did not map to a previously
      mapped modifier on chromosome 19, indicating the presence of additional genes
      impacting disease severity. The previously studied Glial Fibrillary Acidic
      Protein promoter-Npc1 cDNA transgene (GFAP-Npc1) which only expresses NPC1 in
      astrocytes further extended the lifespan of Npc1nmf164 homozygotes on a BALB/cJ
      background (up to 600days). Hydroxypropyl-beta-cyclodextrin (HPbetaCD) treatment,
      not previously tested in the Npc1nmf164 mutant, extended life in the Npc1nmf164
      homozygotes but not the transgenic, Npc1nmf164 mice on the BALB/cJ background. In
      all cases, lack of weight gain and early cerebellar symptoms of loss of motor
      control were found. At termination, the one mouse sacrificed for histological
      studies showed severe, diffuse pulmonary alveolar proteinosis suggesting that
      pulmonary abnormalities in NPC1 mouse models are not unique to the Npc1nih
      allele.

PMID- 29223360
TI  - Impact of positive surgical margins on overall survival after partial nephrectomy
      A matched comparison based on the National Cancer Database.
AB  - INTRODUCTION: The impact of positive surgical margins (PSM) in partial
      nephrectomy (PN) has been a controversy. Previous studies on the relationship
      between PSM and overall survival (OS) were either underpowered or had highly
      dissimilar groups. We used the National Cancer Database with propensity score
      matching to determine the association between PSM and OS after PN. MATERIALS AND
      METHODS: We identified patients with T1/T2 N0M0 renal cancer treated with PN
      between 2004 and 2009, and divided them into 2 groups based on their margin
      status. We used propensity score matching to ensure similarities in age,
      comorbidity score (CCI), tumor size, histology, and grade between groups.
      Covariates were compared by chi2 test. Cox multiple regression was used to
      estimate the hazard ratios (HR) for all-cause mortality. OS between matched
      groups were compared by log-rank, Breslow and Tarone-Ware tests. RESULTS: After
      excluding those with missing data on margin or survival status, 20,762 patients
      were eligible for matching. Each matched group had 1,265 patients, similar in
      age, sex, race, CCI, tumor size, histology, and grade. There were 386 recorded
      all-cause mortalities over a median follow-up duration of 72.6 months. Cox
      multiple regression showed a higher risk of all-cause mortality among cases with
      PSM (HR: 1.393, P = 0.001). Old age, high CCI, and large tumors had higher risks,
      while papillary and chromophore histologic subtypes had lower risks. PSM was
      associated with significantly worse OS by log-rank, Breslow, and Tarone-Ware
      tests. CONCLUSION: PSM is associated with significantly worse OS after PN.

PMID- 29223361
TI  - Evidence Suggests Sphingosine 1-Phosphate Might Be Actively Generated, Degraded,
      and Transported to Extracellular Spaces With Increased S1P2 and S1P3 Expression
      in Colon Cancer.
AB  - BACKGROUND: A pivotal role of sphingosine 1-phosphate (S1P) in cancer has been
      suggested based on the ceramide-S1P rheostat theory that the intracellular
      balance between prosurvival S1P and proapoptotic ceramide determines cell fate.
      Upregulation of S1P-generating sphingosine kinases (SKs) and downregulation of
      S1P-degrading S1P lyase (SPL) might increase intracellular S1P levels to exert a
      prosurvival effect in cancer in general, such as colon cancer. However, we
      recently observed a distinct S1P metabolism in hepatocellular carcinoma tissues
      that increased SPL mRNA levels with reduced S1P levels. Thus, we investigated S1P
      metabolism in colon cancer. PATIENTS AND METHODS: We enrolled 26 consecutive
      colon cancer patients, who had undergone surgical treatment. RESULTS: Not only
      SK, but also SPL, mRNA levels were increased in colon cancer tissues compared
      with the adjacent nontumorous tissues. Furthermore, the mRNA levels of another
      S1P degrading enzyme, S1P phosphatase 1, S1P transporters, spinster homolog 2,
      adenosine triphosphate-binding cassette subfamily C member 1, and S1P receptors,
      S1P2 and S1P3 were also increased, but the S1P levels were not increased in the
      colon cancer tissues. The reduction of SPL expression by silencing led to reduced
      proliferation and invasion, and overexpression of SPL caused enhanced
      proliferation in colon cancer cell lines. CONCLUSION: In human colon cancer
      tissues, mRNA levels of S1P-generating and S1P-degrading enzymes, transporters
      from inside to outside the cells, and S1P receptors, S1P2 and S1P3 were elevated,
      suggesting active S1P metabolism and movement. This altered S1P metabolism might
      play a role in colon cancer pathophysiology.

PMID- 29223362
TI  - Autophagy Inhibition in Pancreatic Adenocarcinoma.
AB  - Although some progress has been made in recent years with the development of more
      effective chemotherapy regimens, new treatment approaches are needed to improve
      outcomes for patients with pancreatic adenocarcinoma. The cellular process of
      autophagy, a cell survival mechanism that allows cancer cells to survive the
      hazardous conditions of the tumor microenvironment and treatment, has emerged as
      a viable target in pancreatic cancer. We review the mechanism of autophagy, its
      role in pancreatic carcinogenesis, the preclinical and clinical evidence
      supporting targeting autophagy in patients with pancreatic adenocarcinoma, and
      areas of future investigation that hold promise for improving this treatment
      approach.

PMID- 29223363
TI  - Comprehensive determinants of growth trajectories and body composition in school
      children: A longitudinal cohort study.
AB  - OBJECTIVE: To fully explain the dynamic and comprehensive etiology of the
      trajectory associated with adiposity indices. METHODS: This study involved data
      of 5572 children, aged 6-11 years, as part of the Taiwan Children Health Study
      (TCHS). The present study introduced four distinct BMI trajectories, identified
      previously among children: persistently healthy weight; late-onset overweight or
      obesity; persistent overweight or obesity; and declining BMI class. Logistic
      regression was used to examine the effect of non-modifiable factors on BMI
      trajectory classes. Generalized estimating equations were used to examine the
      effect of dynamically modifiable factors on either BMI trajectory classes or
      adiposity indices. RESULTS: Compared with class 1 (persistently healthy weight),
      class 2 exhibited a significantly increased risk of weight gain and fat mass,
      affected by lower family incomes and poor-quality sleep. Class 3 had a higher
      risk of persistent obesity and abdominal obesity, affected by higher birthweight
      and sedentary lifestyle. Class 4 approached a healthy weight due to increased
      physical activity, which was associated with a decrease in body fat and central
      obesity. CONCLUSIONS: We found crucially non-modifiable and modifiable factors
      that could describe each high BMI growth pattern, and calculated their modifiable
      contributions to adiposity indices. Modifiable factors that focus on those
      crucially dynamic factors are recommended for preventing obese growth
      trajectories.

PMID- 29223364
TI  - Labial lesion in a Portuguese man returned from Brazil - The role of molecular
      diagnosis.

PMID- 29223365
TI  - Performance of spleen stiffness measurement in prediction of clinical significant
      portal hypertension: A meta-analysis.
AB  - AIM: Our purpose was to evaluate the correlation between spleen stiffness (SS)
      measured by ultrasound-based elastography and hepatic venous pressure gradient
      (HVPG) and assess the accuracy of SS in detecting clinical significant portal
      hypertension (CSPH) and severe portal hypertension. METHOD: Nine studies were
      included from thorough literature research and selection processes. A random
      model was used to analyze the correlation between HVPG and SS. We adopted the
      bivariate mixed effects model to assess the diagnostic performance. RESULTS:
      Regarding to correlation between SS and HVPG, the summary correlation coefficient
      was 0.72 (95% confidence interval [CI], 0.63-0.80). In detection of CSPH, the
      sensitivity, specificity, AUC and DOR were: 0.88 (0.70-0.96), 0.84 (0.72-0.92),
      0.92 (0.89-0.94) and 38 (17-84) for CSPH, respectively; and 0.92 (0.82-0.96),
      0.79 (0.72-0.85), 0.87 (0.84-0.90) and 41 (17-100) for severe portal
      hypertension, respectively. CONCLUSION: Correlation between SS and HVPG was good.
      Although SS showed good sensitivity and specificity, the different cut-off values
      and techniques among studies might limit the impact of our results on clinical
      practice. Therefore, more high-quality prospective studies are required to
      evaluate the role of SS in predicting portal hypertension.

PMID- 29223366
TI  - Therapeutic efficacy and safety of umbilical cord mesenchymal stem cell
      transplantation for liver cirrhosis in Chinese population: A meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Mesenchymal stem cells transfusion has been considered
      as a promising option for liver cirrhosis (LC). The aim of this study was to
      systematically evaluate the efficacy and safety of umbilical cord mesenchymal
      stem cells (UMSC) combined with traditional supportive therapy (TST) for the
      treatment of patients with LC. METHODS: Data was extracted from clinical trials
      published on Web of Science, PubMed, EMBASE, Cochrane Library, Wanfang and CNKI
      database. The evaluated outcome measurements included liver function, coagulation
      function, liver fibrosis indexes, clinical symptoms, quality of life (QOL) and
      adverse events. RESULTS: A total of 14 trials including 717 LC patients met our
      selection criteria were involved. The liver function of LC patients was
      significantly improved after combined therapy (UMSC plus TST), indicated by
      decreased total bilirubin, alanine aminotransferase and prothrombin time, and
      increased serum albumin, cholinesterase and prothrombin activity. The QOL of
      patients was also improved after UMSC therapy. Compared with TST alone, the
      combined therapy showed better treatment effect based on measurements of
      hyaluronic acid (OR=-143.20, CI=-181.58 to -104.82, P<0.00001), laminin (OR=
      50.65, CI=-53.70 to -47.61, P<0.00001), type III procollagen (OR=-8.68, CI=-9.00
      to -8.36, P<0.00001), type IV collagen (OR=-105.79, CI=-132.44 to -79.14,
      P<0.00001) and plasma prolidase (OR=-876.54, CI=-911.89 to -840.56, P<0.00001).
      Moreover, the patients' clinical symptoms including fatigue (4th, P=0.003; 8th,
      P=0.01), appetite (4th, P<0.0001; 8th, P=0.06), ascites (4th, P=0.03; 8th,
      P=0.17), and abdominal distension (4th, P=0.0008; 8th, P=0.64) were also improved
      in patients treated by combined therapy without adverse events observed.
      CONCLUSION: UMSC and TST combined therapy for LC patients improved their liver
      function, clinical symptoms and QOL without severe adverse events, therefore is
      safe and effective in LC therapy.

PMID- 29223367
TI  - Relationship Between Obesity and Survival in Patients Hospitalized for
      Hypertensive Emergency.

PMID- 29223368
TI  - Transport of polymer stabilized nano-scale zero-valent iron in porous media.
AB  - This study presents a set of laboratory-scale transport experiments and numerical
      simulations evaluating carboxymethyl cellulose (CMC) polymer stabilized nano
      scale zero-valent iron (nZVI) transport. The experiments, performed in a glass
      walled two-dimensional (2D) porous medium system, were conducted to identify the
      effects of water specific discharge and CMC concentration on nZVI transport and
      to produce data for model validation. The transport and movement of a tracer
      lissamine green B(r) (LGB) dye, CMC, and CMC-nZVI were evaluated through analysis
      of the breakthrough curves (BTCs) at the outlets, the time-lapsed images of the
      plume, and retained nZVI in the sandbox. The CMC mass recovery was >95% when
      injected alone and about 65% when the CMC-nZVI mixture was used. However, the
      mean residence time of CMC was significantly higher than that of LGB. Of
      significance for field implementation, viscous fingering was observed in water
      displacement of previously injected CMC and CMC-nZVI. The mass recovery of nZVI
      was lower (<50%) than CMC recovery due to attachment onto sand grain surfaces.
      Consecutive CMC-nZVI injections showed higher nZVI recovery in the second
      injection, a factor to be considered in field trials with successive CMC-nZVI
      injections. Transport of LGB, CMC, and nZVI were modeled using a flow and
      transport model considering LGB and CMC as solutes, and nZVI as a colloid, with
      variable solution viscosity due to changes in CMC concentrations. The simulation
      results matched the experimental observations and provided estimates of transport
      parameters, including attachment efficiency, that can be used to predict CMC
      stabilized nZVI transport in similar porous media, although the extent of viscous
      fingering may be underpredicted. The experimental and simulation results
      indicated that increasing specific discharge had a greater effect on decreasing
      CMC-nZVI attachment efficiency (corresponding to greater possible travel
      distances in the field) than increasing CMC concentration.

PMID- 29223369
TI  - A critical review of endpoints for non-cirrhotic NASH therapeutic trials.
AB  - Non-alcoholic steatohepatitis is a disease without a single, specific, diagnostic
      marker, hence multiple indicators are required to measure therapeutic efficacy.
      Moreover, drug candidates for non-alcoholic steatohepatitis target many distinct
      mechanisms that are believed to promote hepatic injury. Therefore, a wide range
      of endpoints must be reached, sequentially, as required by the drug development
      process. Some of these endpoints validate the mechanism of action, others are
      used to anticipate histological efficacy. Histological endpoints are still
      considered the best predictors of clinical outcome, but they can only be reliably
      tested in larger, late phase trials. Herein, we will review the rationale and
      clinical data supporting the use of specific endpoints at different stages of
      therapeutic trials. We will also discuss the validity and limitations of current
      phase IIb histological endpoints, particularly a one stage reduction in fibrosis,
      for their ability to predict progression to cirrhosis, which is the ultimate
      outcome measure in therapeutic trials.

PMID- 29223370
TI  - Four weeks of ledipasvir/sofosbuvir and ribavirin with or without pegylated
      interferon for chronic hepatitis C in non-cirrhotic people who inject drugs. A
      randomized trial.

PMID- 29223371
TI  - Planning and prioritizing direct-acting antivirals treatment for HCV patients in
      countries with limited resources: Lessons from the Egyptian experience.
AB  - BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C
      virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV
      treatment program becoming the largest in the world. The aim of this paper is to
      present the Egyptian experience in planning and prioritizing mass treatment for
      patients with HCV, highlighting the difficulties and limitations of the program,
      as a guide for other countries of similarly limited resources. METHODS: Baseline
      data of 337,042 patients, treated between October 2014 to March 2016 in
      specialized viral hepatitis treatment centers, were grouped into three equal time
      intervals of six months each. Patients were treated with different combinations
      of direct-acting antivirals, with or without ribavirin and pegylated interferon.
      Baseline data, percentage of patients with known outcome, and sustained
      virological response at week 12 (SVR12) were analyzed for the three cohorts. The
      outcomes of 94,258 patients treated in the subsequent two months are also
      included. RESULTS: For cohort-1, treatment was prioritized for patients with
      advanced fibrosis (F3-F4 fibrosis, liver stiffness >=9.5 kPa, or Fibrosis-4
      >=3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The
      prioritization strategy in the initial phase caused delays in enrollment and
      massive backlogs. Cohort-1 patients were significantly older, and more had
      advanced fibrosis compared to subsequent cohorts. The percentage of patients with
      known SVR12 results were low initially, and increased with each cohort, as
      several methods to capture patient results were adopted. Sofosbuvir-ribavirin
      therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies
      were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization
      based on fibrosis stage was not effective and enrollment increased greatly only
      after including all stages of fibrosis. The availability of generic drugs reduced
      costs, and helped massively increase uptake of the program. Post-treatment follow
      up was initially very low, and although this has increased, further improvement
      is still needed. LAY SUMMARY: We are presenting the largest national program for
      HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured
      efficiently in large scale real-life programs. This is a clear statement that
      global HCV eradication is foreseeable, providing a model for other countries with
      limited resources and prevalent HCV. Moreover, the availability of generic
      products has influenced the success of this program.

PMID- 29223373
TI  - Adverse Prognostic Factors for Morbidity and Mortality During Peripheral Blood
      Stem Cell Mobilization in Patients with Light Chain Amyloidosis.
AB  - Patients with immunoglobulin light chain (AL) amyloidosis undergoing peripheral
      blood hematopoietic stem cell (PBSC) mobilization for autologous hematopoietic
      stem cell transplantation (auto-HCT) can experience significant morbidity and
      mortality. The purpose of this study was to characterize the adverse events and
      identify prognostic factors associated with the development of morbidity and
      mortality in patients with AL amyloidosis who had begun PBSC mobilization for
      auto-HCT. A retrospective study was performed in 101 consecutive patients with AL
      amyloidosis who underwent PBSC mobilization for auto-HCT between January 2006 and
      December 2013. A composite primary endpoint of morbidity and mortality during
      PBSC mobilization was used. Forty-one patients (41%) experienced at least 1
      adverse event, including 4 deaths during PBSC mobilization. Adverse events
      included in this composite endpoint were cardiac events, thromboembolic events,
      bleeding events, unplanned hospitalization, weight gain >2% necessitating
      diuretic intervention, and death. Low serum albumin levels, elevated N-terminal
      pro-brain natriuretic peptide, and increased interventricular septal thickness
      were significantly associated with the composite primary endpoint (P = .024,
      .001, and .006, respectively). The median progression-free survival from the
      start of PBSC mobilization was 4.7 years, and the median overall survival was 6.5
      years. In general, PBSC mobilization is associated with minimal complications,
      but patients with AL amyloidosis can experience more frequent and severe
      complications, such as volume overload and weight gain. Careful patient selection
      is warranted in patients with AL amyloidosis before proceeding to PBSC
      mobilization and auto-HCT.

PMID- 29223374
TI  - Cardiac Involvement in a Patient Cohort With Val30Met Mutation Transthyretin
      Amyloidosis.

PMID- 29223372
TI  - Diagnostic and Prognostic Plasma Biomarkers for Idiopathic Pneumonia Syndrome
      after Hematopoietic Cell Transplantation.
AB  - Idiopathic pneumonia syndrome (IPS) is a noninfectious pulmonary complication
      after hematopoietic cell transplantation (HCT) and is difficult to diagnose. In
      41 patients with IPS, we evaluated 6 candidate proteins in plasma samples at day
      7 post-HCT and at onset of IPS to identify potential diagnostic or prognostic
      biomarkers for IPS. Samples at similar times from 162 HCT recipients without
      documented infections and 37 HCT recipients with respiratory viral pneumonia
      served as controls. In multivariable models, a combination of Stimulation-2 (ST2;
      odds ratio [OR], 2.8; P < .001) and IL-6 (OR, 1.4; P = .025) was the best panel
      for distinguishing IPS at diagnosis from unaffected controls, whereas tumor
      necrosis factor receptor 1 (TNFR1; OR, 2.9; P = .002) was the best marker when
      comparing patients with IPS and viral pneumonia. The areas under the curve of the
      receiver operating characteristic (ROC) curves for discriminating between IPS and
      unaffected controls at day 7 post-HCT were .8 for ST2, .75 for IL-6, and .68 for
      TNFR1. Using estimated sensitivity and specificity values from cutoffs determined
      with the ROC analysis (cutoff level: ST2, 21 ng/mL; IL-6, 61 pg/mL; TNFR1, 3421
      pg/mL), we calculated positive predictive values (PPV) for a range of estimated
      population prevalence values of IPS. Among the 3 markers, ST2 showed the highest
      PPV for IPS occurrence. Based on an assumed prevalence of 8%, a positive ST2 test
      increased likelihood of IPS to 50%. We conclude that a prospective validation
      study is warranted to determine whether a plasma biomarker panel can aid the
      noninvasive diagnosis and prognosis of IPS.

PMID- 29223375
TI  - Selection of the Best of 2017 in Heart Failure in Elderly Patients.

PMID- 29223376
TI  - Optical Coherence Tomography of Magnesium Bioresorbable Scaffold Restenosis.

PMID- 29223377
TI  - Analysis of Hospitalization Trends for Heart Failure in the Health Registries of
      Different Autonomous Communities. Response.

PMID- 29223378
TI  - Bioresorbable Vascular Scaffold Thrombosis: Clinical and Optical Coherence
      Tomography Findings.

PMID- 29223379
TI  - Pulmonary Valve Perforation and Stent Implantation in the Right Ventricle Outflow
      Tract Using a Hybrid Procedure as an Alternative to a Central Shunt.

PMID- 29223380
TI  - Large intramural hematoma and gastric ulcer after EMR of a small gastric polyp.

PMID- 29223381
TI  - A case of cecocolonic intussusception after endoscopic submucosal dissection of a
      cecal adenoma.

PMID- 29223382
TI  - Pharyngeal angina bullosa hemorrhagica due to EGD.

PMID- 29223383
TI  - Colon adenoma with 2 too-long stalks (with video).

PMID- 29223384
TI  - A case of hepatic Kaposi's sarcoma diagnosed by transgastric biopsy.

PMID- 29223385
TI  - Mucinous adenocarcinoma of unknown primary presenting with dysphagia.

PMID- 29223386
TI  - Extensive esophageal papillomatosis after chemoradiotherapy for squamous cell
      carcinoma.

PMID- 29223387
TI  - Tolerance levels of PLGA microspheres in the eyes.

PMID- 29223388
TI  - Transplantation in the Treatment of Primary Cutaneous Aggressive Epidermotropic
      Cytotoxic CD8-Positive T-Cell Lymphoma.
AB  - BACKGROUND: Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T
      cell lymphoma (CD8+ PCAETL) is a rare subtype of peripheral T-cell lymphoma with
      poor outcomes and without a standardized treatment strategy. Allogeneic
      hematopoietic stem cell transplantation (HSCT) has been suggested as a potential
      curative therapy. PATIENTS AND METHODS: We conducted a retrospective case series.
      We identified 8 patients with the diagnosis of CD8+ PCAETL, 4 of whom also
      underwent allogeneic HSCT. RESULTS: Eight patients were treated at our center
      with combination chemotherapy and several novel agents, including histone
      deacetylase inhibitors, brentuximab, and pralatrexate. Patients underwent a
      median of 8.5 treatments before HSCT. Six of the 8 patients examined, including
      all 4 who received an HSCT, were alive at their last follow-up. CONCLUSION:
      Allogeneic HSCT is a promising treatment modality for CD8+ PCAETL. Because of the
      aggressive nature of this disease and lack of sustained remission with currently
      available therapies, HSCT should be considered early in the course of treatment.
      Two novel agents, brentuximab and pralatrexate, showed significant activity
      against CD8+ PCAETL, and may be incorporated earlier in the treatment course.

PMID- 29223389
TI  - A Multi-Institutional Prospective Trial Confirms Noninvasive Blood Test Maintains
      Predictive Value in African American Men.
AB  - PURPOSE: The 4Kscore(r) test accurately detects aggressive prostate cancer and
      reduces unnecessary biopsies. However, its performance in African American men
      has been unknown. We assessed test performance in a cohort of men with a large
      African American representation. MATERIALS AND METHODS: Men referred for prostate
      biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the
      study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate
      biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer
      on biopsy. We assessed the discrimination, calibration and clinical usefulness of
      4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a
      base model consisting of age, digital rectal examination and prostate specific
      antigen. Additionally, we compared test performance in African American and
      nonAfrican American men. RESULTS: Of the 366 enrolled men 205 (56%) were African
      American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore
      test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical
      usefulness on decision curve analysis than the base model. Test prediction
      closely approximated the observed risk of Grade Group 2 or higher prostate
      cancer. There was no difference in test performance in African American and
      nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base
      model in each group. CONCLUSIONS: The 4Kscore test accurately predicts aggressive
      prostate cancer for biopsy decision making in African American and nonAfrican
      American men.

PMID- 29223390
TI  - Lymphatic Drainage from Renal Tumors In Vivo: A Prospective Sentinel Node Study
      Using SPECT/CT Imaging.
AB  - PURPOSE: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage
      studies of primary lymphatic landing sites may reveal the variability and
      dynamics of lymphatic connections. The purpose of this study was to investigate
      the lymphatic drainage pattern of renal tumors in vivo with single photon
      emission/computerized tomography after intratumor radiotracer injection.
      MATERIALS AND METHODS: We performed a phase II, prospective, single arm study to
      investigate the distribution of sentinel nodes from renal tumors on single photon
      emission/computerized tomography. Patients with cT1-3 (less than 10 cm) cN0M0
      renal tumors of any subtype were enrolled in analysis. After intratumor
      ultrasound guided injection of 0.4 ml 99mTc-nanocolloid we performed preoperative
      imaging of sentinel nodes with lymphoscintigraphy and single photon
      emission/computerized tomography. Sentinel and locoregional nonsentinel nodes
      were resected with a gamma probe combined with a mobile gamma camera. The primary
      study end point was the location of sentinel nodes outside the locoregional
      retroperitoneal templates on single photon emission/computerized tomography.
      Using a Simon minimax 2-stage design to detect a 25% extralocoregional
      retroperitoneal template location of sentinel nodes on imaging at alpha = 0.05
      and 80% power at least 40 patients with sentinel node imaging on single photon
      emission/computerized tomography were needed. RESULTS: Of the 68 patients 40
      underwent preoperative single photon emission/computerized tomography of sentinel
      nodes and were included in primary end point analysis. Lymphatic drainage outside
      the locoregional retroperitoneal templates was observed in 14 patients (35%).
      Eight patients (20%) had supradiaphragmatic sentinel nodes. CONCLUSIONS: Sentinel
      nodes from renal tumors were mainly located in the respective locoregional
      retroperitoneal templates. Simultaneous sentinel nodes were located outside the
      suggested lymph node dissection templates, including supradiaphragmatic sentinel
      nodes in more than a third of the patients.

PMID- 29223391
TI  - Effects of a hydroethanolic extract of Boophone disticha bulb on anxiety-related
      behaviour in naive BALB/c mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Boophone disticha is one of the most important
      medicinal bulbs of Southern Africa. Previous in vitro studies have shown that
      it's crude ethanolic extracts and some alkaloidal phytoconstituents possesses
      high affinity for the serotonin transporter protein (SERT) and serotonin receptor
      1a (5HT1a) which are both implicated in the pathogenesis and treatment of anxiety
      disorders. However, there are no in vivo studies that validates the anxiolytic
      actions of the plant. AIM OF THE STUDY: This study was therefore set to determine
      the anxiolytic-like activity of an orally administered hydroethanolic extract of
      B. disticha bulbs in naive mice using the behavioural tests of anxiety. MATERIALS
      AND METHODS: Naive adult male BALB/c mice were randomly placed into five
      treatment groups (n=6-10): vehicle control (10ml/kg 0.9% NaCl), positive control
      (1mg/kg diazepam) and the hydroethanolic extract of B. disticha (10, 25 and
      40mg/kg p.o.). Souk test, elevared plus maze and open field tests were used to
      evaluate the anxiolytic-like activity of the B. disticha extract. RESULTS:
      Diazepam-treated mice exhibited higher number of sector visits and line crossings
      in the ST, rearings in the OF and head dips in the EPM than the control (p<0.05).
      B. disticha extract treated groups expressed higher sector visits at 10mg/kg,
      and, unprotected head dips at 25mg/kg in the ST, as well as, open arm time
      entries at 10mg/kg dose, and unprotected head dips at all doses in the EPM than
      the control group (p<0.05). The 25mg/kg B. disticha dose group exhibited highest
      anxiolytic-like activity in both the ST and OF, while the 10mg/kg was most active
      in the EPM. CONCLUSION: The extract of B. disticha exerted good anxiolytic-like
      activity in both the ST and OF at medium dose (25mg/kg), while the low dose
      (10mg/kg) showed prominent anxiolytic-like activity in the EPM.

PMID- 29223392
TI  - Parkinson's disease-associated mutant LRRK2 phosphorylates Rab7L1 and modifies
      trans-Golgi morphology.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the major genetic cause of
      autosomal-dominantly inherited Parkinson's disease. LRRK2 is implicated in the
      regulation of intracellular trafficking, neurite outgrowth and PD risk in
      connection with Rab7L1, a putative interactor of LRRK2. Recently, a subset of Rab
      GTPases have been reported as substrates of LRRK2. Here we examine the kinase
      activity of LRRK2 on Rab7L1 in situ in cells. Phos-tag analyses and metabolic
      labeling assays revealed that LRRK2 readily phosphorylates Golgi-localized wild
      type Rab7L1 but not mutant forms that are distributed in the cytoplasm. In vitro
      assays demonstrated direct phosphorylation of Rab7L1 by LRRK2. Subsequent
      screening using Rab7L1 mutants harboring alanine-substitution for every single
      Ser/Thr residue revealed that Ser72 is a major phosphorylation site, which was
      confirmed by using a phospho-Ser72-specific antibody. Moreover, LRRK2 pathogenic
      Parkinson mutants altogether markedly enhanced the phosphorylation at Ser72. The
      modulation of Ser72 phosphorylation in Rab7L1 resulted in an alteration of the
      morphology and distribution of the trans-Golgi network. These data collectively
      support the involvement of Rab7L1 phosphorylation in the LRRK2-mediated cellular
      and pathogenetic mechanisms.

PMID- 29223393
TI  - Mersalyl prevents the Tl+-induced permeability transition pore opening in the
      inner membrane of Ca2+-loaded rat liver mitochondria.
AB  - It was earlier shown that the calcium load of rat liver mitochondria in medium
      containing TlNO3 and KNO3 resulted in the Tl+-induced mitochondrial permeability
      transition pore (MPTP) opening in the inner membrane. This opening was
      accompanied by an increase in swelling and membrane potential dissipation and a
      decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration. This
      respiratory decrease was markedly leveled by mersalyl (MSL), the phosphate
      symporter (PiC) inhibitor which poorly stimulated the calcium-induced swelling,
      but further increased the potential dissipation. All of these effects of Ca2+ and
      MSL were visibly reduced in the presence of the MPTP inhibitors (ADP, N
      ethylmaleimide, and cyclosporine A). High MSL concentrations attenuated the
      ability of ADP to inhibit the MPTP. Our data suggest that the PiC can participate
      in the Tl+-induced MPTP opening in the inner membrane of Ca2+-loaded rat liver
      mitochondria.

PMID- 29223394
TI  - Islet beta cell: An endocrine cell secreting miRNAs.
AB  - The pancreas is an important endocrine organ. Pancreatic beta (beta) cells
      secrete insulin to regulate the metabolism of glucose and maintain the stability
      of blood glucose. MicroRNAs (miRNAs), small (20-25 nt) non-coding RNA molecules,
      function in target gene silencing through post-transcriptional patterns, and
      multiple miRNAs regulate insulin secretion, insulin signaling pathways in
      pancreatic beta cells and islet activity. In recent years, it has been found that
      many types of cells can secrete regulatory miRNA, but whether islet cells can
      secrete miRNA has not been clarified yet. In this study, we detected miRNA
      expressions in cell culture medium of primary mouse islet cells and islet cell
      line MIN6. And we found that islet cells can selectively and actively secrete
      miRNAs, mainly through the way of exosome package, and that miRNA secretion
      profiling patterns vary according to different insulin secretion stimulating
      conditions (high Glucose, high Kcl, high Arginine and high Free fat acid (FFA)).
      Additionally, we found that these miRNAs secreted by islet cells can be
      transported and have gene-regulating functions on recipient tissue cells, such as
      liver and muscles. In conclusion, we find another secretory function of the islet
      beta cells: not only insulin, but also miRNAs.

PMID- 29223395
TI  - A novel mouse model for tracking the fate of CXCR5-expressing T cells.
AB  - The germinal center (GC) reaction, a critical process in the humoral immune
      response, requires follicular helper T (Tfh) cells. Tfh cells express the master
      transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to
      migrate from the T cell zone to B cell follicles and interact with GC B cells.
      However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it
      is difficult to track Tfh cells continuously in vivo. In this study, we generated
      a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato
      is inducibly expressed in CXCR5+ cells by tamoxifen administration. After the
      oral administration of tamoxifen, most Tfh cells in Peyer's patches (PP) from
      Cxcr5CreERT2R26Tomato mice were tdTomato+. To track antigen-specific Tfh cells in
      vivo, OVA-specific OT-II T cells derived from Cxcr5CreERT2R26Tomato mice were
      transferred to wild-type mice, and the recipient mice were immunized with OVA
      followed by tamoxifen administration. CXCR5+ T cells became tdTomato+ and were
      mainly located in B cell follicles and GC areas 8 days after immunization. Four
      weeks after immunization, tdTomato+ OT-II T cells migrated from B cell follicles
      to the T-B border area and T cell zone after CXCR5 downregulation and CCR7
      upregulation. These results indicate that Cxcr5CreERT2R26Tomato mice are a useful
      tool for studying the cell fate of differentiated Tfh cells in vivo and therefore
      have implications for the development of therapeutic strategies for infectious
      and autoimmune diseases.

PMID- 29223396
TI  - Accelerated dentinogenesis by inhibiting the mitochondrial fission factor,
      dynamin related protein 1.
AB  - Undifferentiated odontogenic epithelium and dental papilla cells differentiate
      into ameloblasts and odontoblasts, respectively, both of which are essential for
      tooth development. These differentiation processes involve dramatic functional
      and morphological changes of the cells. For these changes to occur, activation of
      mitochondrial functions, including ATP production, is extremely important. In
      addition, these changes are closely related to mitochondrial fission and fusion,
      known as mitochondrial dynamics. However, few studies have focused on the role of
      mitochondrial dynamics in tooth development. The purpose of this study was to
      clarify this role. We used mouse tooth germ organ cultures and a mouse dental
      papilla cell line with the ability to differentiate into odontoblasts, in
      combination with knockdown of the mitochondrial fission factor, dynamin related
      protein (DRP)1. In organ cultures of the mouse first molar, tooth germ developed
      to the early bell stage. The amount of dentin formed under DRP1 inhibition was
      significantly larger than that of the control. In experiments using a mouse
      dental papilla cell line, differentiation into odontoblasts was enhanced by
      inhibiting DRP1. This was associated with increased mitochondrial elongation and
      ATP production compared to the control. These results suggest that DRP1
      inhibition accelerates dentin formation through mitochondrial elongation and
      activation. This raises the possibility that DRP1 might be a therapeutic target
      for developmental disorders of teeth.

PMID- 29223397
TI  - (+)-Borneol suppresses conditioned fear recall and anxiety-like behaviors in
      mice.
AB  - Fear- and anxiety-related psychiatric disorders have been one of the major
      chronic diseases afflicting patients for decades, and new compounds for treating
      such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found
      in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety,
      pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (gamma
      aminobutyric acid) activity directly in recombinant GABAA receptors. The present
      study was to investigate the effects of (+)-Borneol on both contextual and cued
      fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal
      hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into
      ventral hippocampus only reduced 24 h cued fear responses. Moreover,
      microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed
      anxiety-like behaviors in the open field test, light/dark exploration and the
      elevated plus maze test. As selective GABAA receptor antagonist bicuculline
      reversed the effect of (+)-Borneol on contextual fear paradigm and the drug
      potentiated GABA-evoked currents in acute hippocampus slices, modulation of the
      GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings
      suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety
      related disorders.

PMID- 29223398
TI  - EphA7 regulates claudin6 and pronephros development in Xenopus.
AB  - Eph/ephrin molecules are widely expressed during embryonic development, and
      function in a variety of developmental processes. Here we studied the roles of
      the Eph receptor EphA7 and its soluble form in Xenopus pronephros development.
      EphA7 is specifically expressed in pronephric tubules at tadpole stages and
      knockdown of EphA7 by a translation blocking morpholino led to defects in tubule
      cell differentiation and morphogenesis. A soluble form of EphA7 (sEphA7) was also
      identified. Interestingly, the membrane level of claudin6 (CLDN6), a tetraspan
      transmembrane tight junction protein, was dramatically reduced in the translation
      blocking morpholino injected embryos, but not when a splicing morpholino was
      used, which blocks only the full length EphA7. In cultured cells, EphA7 binds and
      phosphorylates CLDN6, and reduces its distribution at the cell surface. Our work
      suggests a role of EphA7 in the regulation of cell adhesion during pronephros
      development, whereas sEphA7 works as an antagonist.

PMID- 29223399
TI  - Ectopic serotonin production in beta-cell specific transgenic mice.
AB  - Genetically modified mice have been widely used in the field of beta-cell
      research. However, analysis of results gathered using genetically modified
      organisms should be interpreted carefully as the results may be confounded by
      several factors. Here, we showed the ectopic serotonin (5-HT) production in beta
      cells of RIP-CreMgn, MIP-GFP, and MIP-Cre/ERT mice. These mice contained a human
      growth hormone (hGH) cassette to enhance transgene expression and hGH expression
      and Stat5 phosphorylation were detected in pancreatic islets of these mice. The
      expression level of tryptophan hydroxylase 1 (Tph1) was upregulated in pancreatic
      islets of transgenic mice with an hGH cassette but not in transgenic mice without
      an hGH cassette. Ectopic 5-HT production was not observed in beta-cell-specific
      prolactin receptor (Prlr) knockout mice or Stat5 knockout mice crossed with RIP
      CreMgn. We further confirmed that 5-HT production in beta-cells of several
      transgenic mice was induced by hGH expression followed by the activation of the
      Prlr-Stat5-Tph1 pathway. These findings indicate that results obtained using
      transgenic mice containing the hGH cassette should be interpreted with care.

PMID- 29223400
TI  - A new comprehensive method for detection of livestock-related pathogenic viruses
      using a target enrichment system.
AB  - We tested usefulness of a target enrichment system SureSelect, a comprehensive
      viral nucleic acid detection method, for rapid identification of viral pathogens
      in feces samples of cattle, pigs and goats. This system enriches nucleic acids of
      target viruses in clinical/field samples by using a library of biotinylated RNAs
      with sequences complementary to the target viruses. The enriched nucleic acids
      are amplified by PCR and subjected to next generation sequencing to identify the
      target viruses. In many samples, SureSelect target enrichment method increased
      efficiencies for detection of the viruses listed in the biotinylated RNA library.
      Furthermore, this method enabled us to determine nearly full-length genome
      sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value
      indicating the ratio of the mapping consensus length in the reference genome, in
      pig samples. Our data showed usefulness of SureSelect target enrichment system
      for comprehensive analysis of genomic information of various viruses in field
      samples.

PMID- 29223401
TI  - Palliative Care Need and Availability in Four Referral Hospitals in Senegal:
      Results from a Multicomponent Assessment.
AB  - CONTEXT: With prevalence of noncommunicable diseases and life expectancy rising
      in Senegal, the need for palliative care is likely growing. No national
      palliative care needs assessments have been carried out. OBJECTIVES: To assess
      the capacity and need for palliative care in Senegal. METHODS: A multicomponent
      assessment of availability and demand for palliative care was conducted in two
      tertiary and two regional hospitals in Senegal in 2015 with approval from
      Senegal's National Ethics Committee for Health Research. The assessment consisted
      of (1) an inpatient hospital census; (2, 3) surveys of inpatients and outpatients
      with life-limiting illness; (4) a knowledge, attitudes, and practices survey
      among health care workers; and (5) a facility survey to assess availability of
      palliative care medications. RESULTS: Nearly half (44.4%) of all inpatients (n =
      167) had an active life-limiting illness. Among them, 56.6% reported moderate-to
      severe pain in the past three days, 2.3% of whom received morphine, and 76.7%
      received weak or no pain medication. Inpatients also experienced moderate-to
      severe dyspnea (42.1%), fatigue (66.5%), nausea (16.5%), and drowsiness (42.1%).
      About 39.2% of all outpatients (n = 395) reported moderate-to-severe pain, and
      52.8% reported that the treatment they had received relieved their pain only
      partially or not at all. Two-thirds of all doctors reported feeling comfortable
      prescribing pain medicines; however, 83.0% rarely or never prescribed morphine.
      Two of four hospitals reported no use of morphine in 2014. CONCLUSION: There is
      significant need for palliative care in Senegal. Training of health care workers
      and ensuring availability of relevant medications should be prioritized.

PMID- 29223402
TI  - Genetic regulation mechanism of the yjdF riboswitch.
AB  - The yjdF riboswitch resides in potential 5' UTRs of homologues of protein-coding
      gene yjdF in Firmicutes. Unlike other 30 riboswitch classes previously validated,
      this riboswitch class, can sense and bind to a broad collection of azaaromatic
      ligands. Among these compounds, some do activate production of yjdF protein
      driven by the riboswitch, while others are out of riboswitch-mediated modulation
      possibly because of the toxicity at high ligand concentrations. By incorporating
      the structures with pseudoknots and ligand binding kinetics into the co
      transcriptional folding theory, we theoretically studied the co-transcriptional
      folding behaviors of the yjdF riboswitch from Bacillus subtilis at different
      transcription conditions. Like most riboswitches, the yjdF riboswitch can quickly
      fold into the aptamer structure without any trapped states during the
      transcription process. After the aptamer structure is formed, the riboswitch
      shows two main co-transcriptional folding pathways: aptamer->ON state->OFF state
      and aptamer -> the ligand bound aptamer -> the ligand bound ON state. Our results
      suggested that this translational riboswitch is coupled with the transcription
      process to exert its biological function and it is kinetically controlled. The
      threshold concentration for the ligand to activate the riboswitch depends on the
      transcription rate and the association rate of the ligand binding.

PMID- 29223403
TI  - Older Adults Undergoing Total Hip or Knee Arthroplasty: Chronicling Changes in
      Their Multimorbidity Profile in the Last Two Decades.
AB  - BACKGROUND: Despite the ubiquitous use of total hip arthroplasty (THA) and total
      knee arthroplasty (TKA) in older adults, little is known about the multimorbidity
      (MM) profile of this patient population. This study evaluates the temporal trends
      of MM, hypothesizing that patients with MM have had an increasingly greater
      representation in THA and TKA patients over time. METHODS: Data on a US
      representative sample of older adults from the linked Health and Retirement Study
      and Medicare data from 1993 to 2012 were used. The Health and Retirement Study is
      a biennial survey that collects data on a broad array of measures, including self
      reported chronic conditions and geriatric syndromes, which were used to account
      for MM. Medicare data were used to identify fee-for-service Medicare
      beneficiaries who underwent THA (n = 479) or TKA (n = 998) during the study
      years, which were grouped into 3 periods: 1993-1999, 2000-2006, and 2007-2012.
      Multivariable logistic regression analysis was conducted to obtain age-, gender-,
      and race-adjusted time trends for MM. RESULTS: Compared to the earliest study
      period, and for both THA and TKA patients, there were significantly fewer
      patients with stroke and/or poor cognitive performance in the most recent study
      period. In addition, more TKA than THA patients presented with 2+ chronic
      conditions. Nearly 70% presented with co-occurring chronic conditions and
      geriatric syndromes, and this percentage did not change significantly over time.
      CONCLUSION: The high representation of THA and TKA patients presenting with co
      occurring chronic conditions and geriatric syndromes in this patient population
      warrants detailed exploration of the effects of geriatric syndromes on
      postoperative outcomes.

PMID- 29223404
TI  - Computer-Assisted Total Knee Arthroplasty: Is There a Difference Between Image
      Based and Imageless Techniques?
AB  - BACKGROUND: Image-based and imageless computer-assisted total knee arthroplasty
      (CATKA) has become increasingly popular. This study aims to compare outcomes,
      including perioperative complications and transfusion rate, between CATKA and
      conventional total knee arthroplasty (TKA), as well as between image-based and
      imageless CATKA. METHODS: Using the 9th revision of the International
      Classification of Diseases codes, we queried the Nationwide Inpatient Sample
      database from 2005 to 2011 to identify unilateral conventional TKA, image-based,
      and imageless CATKAs as well as in-hospital complications and transfusion rates.
      RESULTS: A total of 787,809 conventional TKAs and 13,246 CATKAs (1055 image-based
      and 12,191 imageless) were identified. The rate of CATKA increased 23.13% per
      year from 2005 to 2011. Transfusion rates in conventional TKA and CATKA cases
      were 11.73% and 8.20% respectively (P < .001) and 6.92% in image-based vs 8.27%
      in imageless (P = .023). Perioperative complications occurred in 4.50%, 3.47%,
      and 3.41% of cases after conventional, imageless, and imaged-based CATKAs,
      respectively. Using multivariate analysis, perioperative complications were
      significantly higher in conventional TKA compared to CATKA (odds ratio = 1.17,
      95% confidence interval 1.03-1.33, P = .01). There was no significant difference
      between imageless and image-based CATKA (P = .34). Length of hospital stay and
      hospital charges were not significantly different between groups (P > .05).
      CONCLUSION: CATKA has low complication rates and may improve patient outcomes
      after TKA. CATKA, especially the image-based technique, may reduce in-hospital
      complications and transfusion without increasing hospital charges and length of
      hospital stay significantly. Large prospective studies with long follow-up are
      required to verify potential benefits of CATKA.

PMID- 29223405
TI  - Polished, Collarless, Tapered, Cemented Stems for Primary Hip Arthroplasty May
      Exhibit High Rate of Periprosthetic Fracture at Short-Term Follow-Up.
AB  - BACKGROUND: Cemented stems are designed to follow 1 of 2 principles of fixation:
      composite beams or slide taper. Stems in the latter category have a collarless,
      polished, tapered (CPT) design and subside into the cement mantle, creating hoop
      stresses. We compared the rate of periprosthetic fracture (PPF) of stem designed
      with these 2 principles of fixation. In addition, we examined radiographic
      factors that may predispose to the development of PPF. METHODS: We
      retrospectively reviewed all patients who underwent primary THA by a single
      surgeon using highly polished cemented stems. PPF rates were compared between CPT
      stems (follow-up, 21 months; standard deviation [SD], 22) and composite beam
      stems (follow-up, 21.7 months; SD, 26). Demographic data were compared between
      patients with and without a PPF. Three preoperative radiographic parameters
      (canal bone ratio [CBR], canal-calcar ratio, and canal flare index), stem
      alignment, and cement mantle were compared in match-paired patients with and
      without a PPF (1:34). RESULTS: Seven of 1460 THA patients developed a PPF
      (0.479%); 4 hips of 185 with a CPT stem (2.2%); and 3 of 1275 hips with a
      composite beam stem (0.23%; P = .0064). Three of the 4 PPFs in the CPT group and
      none in the composite beam group were classified as Vancouver B2. The CBR in
      patients with a PPF was 0.50 (SD, 0.07) and 0.43 (SD, 0.07) in the match cohort
      of hips without PPF (P = .013). CONCLUSION: CPT stems may be associated with a
      higher risk of PPF that often require reoperation. An increased CBR may be a risk
      factor for postoperative PPF.

PMID- 29223406
TI  - Chronic Granulomatous Disease in children: a single center experience.
AB  - Chronic Granulomatous Disease (CGD) is caused by the failure of the phagocytes to
      kill pathogens. We carried out a retrospective analysis of cellular, molecular
      and clinical features of 14 young patients (mean age at the onset of symptoms and
      diagnosis: 10 and 25months, respectively), 7 with autosomal recessive and 7 X
      linked form, referred to the Children's Hospital of Brescia between 1999 and
      2016. Two new mutations were found, one localized in the CYBB and one in the NCF1
      genes. Twelve patients were followed in our institution; the average length of
      their follow-up after diagnosis was 66months in X-linked patients and 126months
      in autosomal recessive inheritance. The overall survival was 67%, 40% in X-linked
      and 86% in autosomal recessive form. Eight patients were treated with HSCT. We
      did not find a clear correlation between the clinical symptoms and the type of
      mutation, but the fine characterization of the patients was mandatory for
      therapeutic option, genetic counseling and prenatal diagnosis.

PMID- 29223407
TI  - STAT3-mediated epigenetic silencing of FOXP3 in LADA T cells is regulated through
      HDAC5 and DNMT1.
AB  - In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4+ T cells,
      but the etiology remains unclear. Our study included in 20 LADA patients and 20
      healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1,
      DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4+ T cells than
      controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and
      DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR
      suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3
      acetylation at K9 and K14 of FOXP3 promoter were significantly lower than
      controls. Luciferase reporter assay showed that ectopic STAT3 expression
      significantly reduced FOXP3 promoter activities. The Foxp3 promoter was
      significantly hypermethylated in LADA than controls. LADA patients showed
      stronger binding of p-STAT3, HDAC5 and DNMT1 than controls using CHIP. These
      findings reveal a crucial role of STAT3 in regulating the epigenetic status of T
      cells in LADA.

PMID- 29223408
TI  - Clinical outcomes to exercise training in type 1 diabetes: A systematic review
      and meta-analysis.
AB  - AIMS: To establish the relationship between exercise training and clinical
      outcomes in people with type I diabetes. METHODS: Studies were identified through
      a MEDLINE search strategy, Cochrane Controlled Trials Registry, CINAHL,
      SPORTDiscus and Science Citation Index. The search strategy included a mix of key
      concepts related to trials of exercise training in people with type 1 diabetes;
      glycaemic control. Searches were limited to prospective randomized or controlled
      trials of exercise training in humans with type 1 diabetes lasting 12  weeks or
      more. RESULTS: In exercised adults there were significant improvements in body
      mass Mean Difference (MD): -2.20 kg, 95% Confidence Interval (CI) -3.79-0.61, p =
      .007; body mass index (BMI) MD: -0.39 kg/m2, 95% CI -0.75-0.02, p = .04; Peak VO2
      MD: 4.08 ml/kg/min, 95% CI -2.18-5.98, p < .0001; and, low-density lipoprotein
      cholesterol (LDL) MD: -0.21 mmol/L, 95% CI -0.33-0.08, p = .002. In exercised
      children there were significant improvements in insulin dose MD: -0.23 IU/kg, 95%
      CI -0.37-0.09, p = .002; waist circumference MD: -5.40 cm, 95% CI -8.45 to -2.35,
      p = .0005; LDL MD: -0.31 mmol/L, 95% CI -0.55 to -0.06, p = .02; and,
      triglycerides MD: -0.21 mmol/L, 95% CI -0.42 to -0.01, p = .04. There were no
      significant changes in glycosylated haemoglobin (HbA1C%), fasting blood glucose,
      resting heart rate, resting systolic blood pressure or high density lipoproteins
      in either group. CONCLUSIONS: Exercise training improves some markers of type 1
      diabetes severity; particularly body mass, BMI, Peak VO2 and LDL in adults and
      insulin dose, waist circumference, LDL and triglycerides in children.

PMID- 29223409
TI  - Obtaining Adequate Tension for Extensor Hallucis Longus Tendon Rupture Repair
      Using Wide-Awake Surgery: A Case Report.
AB  - Wide-awake surgery has potential advantages for treating extensor or flexor
      tendon injury. We present a case of chronic extensor hallucis longus injury
      treated with turn-down reconstruction using wide-awake surgery with a selective
      nerve block. To the best of our knowledge, this is the first such case reported.
      The patient had dropped a knife proximal to the right hallux metatarsophalangeal
      joint. Because direct suturing was thought to be difficult, turn-down
      reconstruction was performed under a selective nerve block. At 8 months
      postoperatively, the hallux had 75 degrees  of extension in the
      metatarsophalangeal joint and -5 degrees  of extension in the interphalangeal
      joint, similar to those of the healthy foot. The Japanese Society for Surgery of
      the foot objective hallux scale score had improved from 87 to 100, and the
      subjective scores in the subcategories of pain and pain-related, physical
      functioning and daily living, and shoe-related in the self-administered foot
      evaluation questionnaire had improved from 82.8 to 94.4, 97.7 to 100, and 50 to
      83.3, respectively. Turn-down reconstruction using wide-awake surgery with a
      selective nerve block can be used for chronic extensor hallucis longus rupture
      and can be expected to provide good results.

PMID- 29223411
TI  - Animal models in autism research: The legacy of Paul H. Patterson.

PMID- 29223412
TI  - Resident Education in Pediatric and Adolescent Gynecology.

PMID- 29223410
TI  - Characteristics of computed tomography perfusion parameters in non-small-cell
      lung-cancer and its relationship to histology, size, stage an treatment response.
AB  - OBJECTIVES: To analyze computed tomography perfusion (CTP) parameters in NSCLC.
      MATERIALS AND METHODS: Prospective study, 152 patients with NSCLC. CTP parameters
      were correlated with histology, stage, size and response to conventional
      chemotherapy/radiotherapy. RESULTS: Neuroendocrine tumours presented higher BV (p
      0.002). Negative correlation of PMB (p 0.003) and positive of MTT (p 0.046) with
      T stage was found. BF showed negative correlation with size. No differences were
      found with the RECIST levels of response to chemotherapy/radiotherapy.
      CONCLUSIONS: CTP parameters were highly variable. Neuroendocrine tumours
      presented higher BV and PMB values. Perfusion parameters do not differ depending
      on the stage and do not predict response to treatment.

PMID- 29223413
TI  - Predictors of pressure ulcer risk in adult intensive care patients: A
      retrospective case-control study.
AB  - OBJECTIVES: To evaluate the predictive power of risk factors for pressure ulcers
      in adult intensive care patients. METHOD: A retrospective case-control study was
      performed utilising a heterogeneous sample group allocated into a case group with
      pressure ulcers (n=90) and a control group without pressure ulcers (n=90). The
      analysis explored the predictive power of risk factors for pressure ulcers using
      a hierarchical logistic regression model. RESULTS: The risk factors that
      predicted pressure ulcers were friction (OR=5.97), previous history of pressure
      ulcers (OR=5.43), prolonged intensive care unit stay (OR=3.92), dehydration
      (OR=3.18), elevated skin temperature by 1-2 degrees C (OR=3.12) and treatment of
      other comorbidities (OR=2.79). CONCLUSION: Adult intensive care patients have an
      increased risk of developing a pressure ulcer. These risk factors are regarded as
      strong predictors for pressure ulceration. This study advances nursing knowledge
      in that it investigates additional risk factors for the development of pressure
      ulcers and it identifies a set of factors that best predict their occurrence,
      which may contribute to the nurses' diagnostic reasoning in the intensive care
      unit.

PMID- 29223414
TI  - Juvenile myoclonic epilepsy - An insider's guide.

PMID- 29223415
TI  - [Psychological impact of prostate cancer on patients receiving a 6-month androgen
      deprivation therapy].
AB  - BACKGROUND: Prostate cancer (PCa) is often associated with psychopathological
      symptoms such as anxiety. This study evaluated the effects of the luteinizing
      hormone-releasing hormone agonist therapy leuprorelin acetate (LA) on anxiety and
      quality of life (QoL) over time in men with PCa. METHODS: This observational, non
      interventional, multicenter study was conducted in France. Patients with PCa
      eligible for therapy with a 6-month LA depot were enrolled. Patients completed
      questionnaires assessing anxiety (memorial anxiety scale for prostate cancer [MAX
      PC] ; state trait anxiety inventory [STAI]) and QoL (medical outcomes study 12
      item short-form health survey [SF-12] physical summary component [PCS] and mental
      component summary [MSCS] subscales) at baseline and 6 months after 6-month LA
      depot administration. RESULTS: Questionnaires were completed by 575 men at
      baseline and 315 men at 6 months. Mean age was 75.5 years; median time since
      first diagnosis was 0.4 years. At baseline, the mean (+/-standard deviation [SD])
      MAX-PC score was 17.7+/-12.0, with anxiety primarily related to the PCa
      diagnosis. STAI-state and MAX-PC scores were consistent. Following 6 months of LA
      administration, the mean MAX-PC score decreased (-2.0+/-10.4 ; P<0.001). The PCa
      diagnosis negatively affected patients' QoL, as assessed by the SF-12 PCS and MCS
      subscores. At 6 months, the SF-12 vitality score significantly increased (1.2+/
      9.8; P=0.0142) vs baseline and the SF-12 PCS score decreased by -2.0+/-8.0 from
      baseline. CONCLUSION: After 6 months of leuprorelin 45mg therapy, prostate cancer
      patients appeared to be less anxious with a mental health improvement. LEVEL OF
      EVIDENCE: 3.

PMID- 29223416
TI  - Cost Variation Across Centers for the Norwood Operation.
AB  - BACKGROUND: The Norwood operation is associated with high health care
      utilization, and prior studies reported substantial variability in Norwood costs
      across centers. However, specific factors driving this cost variation are
      unclear. We assessed center variability in Norwood costs and underlying
      mechanisms in a multicenter cohort. METHODS: Clinical data from the Pediatric
      Heart Network Single Ventricle Reconstruction trial were linked with cost data
      from the Children's Hospital Association Inpatient Essentials database. Center
      variation was assessed by modeling Norwood costs adjusted for baseline patient
      characteristics, and the relationship with complications, length of stay (LOS),
      and specific cost categories was examined. Patients undergoing transplantation or
      stage 2 palliation during the Norwood admission were excluded. RESULTS: Nine
      centers (332 patients) were included. Adjusted mean cost/case varied 4.6-fold
      across centers (range: $50,559 to $230,851, p < 0.001). In addition, variation
      was found across centers in the adjusted mean number of complications/case (2.6
      fold variation) and adjusted mean LOS/case (1.9-fold variation). Differences in
      complications explained 63% of the cost variation across centers. After
      accounting for complications, differences in LOS explained 66% of the remaining
      cost variation. Seven specific complications were found to occur more frequently
      at high-cost centers: pleural effusion, seizures, wound infection, thrombus,
      liver dysfunction, sepsis, necrotizing enterocolitis (all p < 0.001). With regard
      to types of cost, room and board/supplies and laboratory costs were the primary
      drivers of cost variation across centers. CONCLUSIONS: This study identified
      several factors associated with center variation in Norwood costs, which may be
      targeted in subsequent initiatives aimed at both improving quality of care and
      reducing costs.

PMID- 29223417
TI  - Left-Ventricular Assist Device Impact on Aortic Valve Mechanics, Proteomics and
      Ultrastructure.
AB  - BACKGROUND: Aortic regurgitation is a prevalent, detrimental complication of left
      ventricular assist devices (LVADs). The altered hemodynamics of LVADs results in
      aortic valves (AVs) having distinct mechanical stimulation. Our hypothesis was
      that the altered AV hemodynamics modulates the valve cells and matrix, resulting
      in changes in valvular mechanical properties that then can lead to regurgitation.
      METHODS: AVs were collected from 16 LVAD and 6 non-LVAD patients at time of heart
      transplant. Standard demographic and preoperative data were collected and
      comparisons between the two groups were calculated using standard statistical
      methods. Samples were analyzed using biaxial mechanical tensile testing, mass
      spectrometry-based proteomics, and transmission electron microscopy to assess
      ultrastructure. RESULTS: The maximum circumferential leaflet strain in LVAD
      patients was less than in non-LVAD patients (0.35 +/- 0.10MPa versus 0.52 +/-
      0.18 MPa, p = 0.03) with a trend of reduced radial strain (p = 0.06) and a
      tendency for the radial strain to decrease with increasing LVAD duration (p =
      0.063). Numerous proteins associated with actin and myosin, immune signaling and
      oxidative stress, and transforming growth factor beta were increased in LVAD
      patients. Ultrastructural analysis showed a trend of increased fiber diameter in
      LVAD patients (46.2 +/- 7.2 nm versus 45.1 +/- 6.9 nm, p = 0.10), but no
      difference in fiber density. CONCLUSIONS: AVs in LVAD patients showed decreased
      compliance and increased expression of numerous proteins related to valve
      activation and injury compared to non-LVAD patients. Further knowledge of AV
      changes leading to regurgitation in LVAD patients and the pathways by which they
      occur may provide an opportunity for interventions to prevent and/or reverse this
      detrimental complication.

PMID- 29223418
TI  - Should Diabetes Be a Contraindication to Bilateral Internal Mammary Artery
      Grafting?
AB  - BACKGROUND: This study evaluates the influence of bilateral internal mammary
      artery (BIMA) versus single internal mammary artery (SIMA) grafting on
      postoperative morbidity and long-term survival among diabetic patients undergoing
      coronary artery bypass grafting (CABG). METHODS: A multicenter, retrospective
      analysis of 47,984 consecutive CABGs performed from 1992 to 2014 at 7 medical
      centers was conducted. Among the study population, 1,482 CABGs with BIMA were
      identified, and 1,297 BIMA patients were propensity-matched to 1,297 SIMA
      patients. The study cohort for this analysis, drawn from matched data, included
      430 diabetic patients: 217 SIMA and 213 BIMA. The primary endpoint was long-term
      survival. Secondary endpoints included postoperative morbidity, length of stay,
      and in-hospital mortality. RESULTS: The median duration of follow-up was 9.3
      (range, 4.3 to 13.9) years. Among propensity-matched diabetic patients, there was
      no significant difference in age, body mass index, or major baseline
      comorbidities. The groups were also well matched on the number of diseased
      coronary arteries and number of distal anastomoses performed. There was no
      difference in the rate of mediastinitis or sternal dehiscence (p = 0.503) or in
      hospital mortality (p = 0.758) between groups. Both groups had a similar median
      length of stay of 5 (range, 4 to 7) days. Diabetic patients who received a BIMA
      had significantly improved long-term survival when compared with SIMA patients
      (hazard ratio 0.75 [95% confidence interval 0.57 to 0.98], p = 0.034).
      CONCLUSIONS: Among diabetics undergoing CABG, use of BIMA grafting does not
      result in increased in-hospital morbidity or mortality and confers a long-term
      survival advantage when compared with SIMA grafting. Thus, diabetic patients
      should be considered for BIMA grafting more frequently.

PMID- 29223419
TI  - Posttransplant Lymphoproliferative Disorders in Epstein-Barr Virus Donor
      Positive/Recipient Negative Lung Transplant Recipients.
AB  - BACKGROUND: Epstein-Barr virus (EBV) donor positive/recipient negative (D+/R-)
      status is a significant risk factor for posttransplant lymphoproliferative
      disorder (PTLD) in lung transplant. There are, however, no studies that identify
      the risk factors for PTLD in the EBV D+/R- lung transplant population to guide
      the decision to proceed with an EBV-positive donor. METHODS: This was a
      retrospective cohort study of adults listed in the Scientific Registry of
      Transplant Recipients between May 5, 2005, and August 31, 2016. Cox proportional
      hazards models were used to assess the impact of EBV D+/R- status on the
      development of PTLD, the impact of PTLD on survival, and survival differences
      between EBV D+/R- and EBV D-/R- recipients. RESULTS: The incidence of PTLD was
      6.2% (79 of 1,281) versus 1.4% (145 of 10,352) in EBV D+/R- versus all other
      recipients (adjusted odds ratio 4.0; 95% confidence interval: 2.8 to 5.9, p <
      0.001). Among EBV D+/R- recipients, age less than 40 years and white race were
      associated with PTLD. The EBV D+/R- patients who had PTLD had increased adjusted
      risk of death (hazard ratio 1.91; 95% confidence interval: 1.35 to 2.71; p <
      0.001). Compared with EBV D+/R- recipients, EBV D-/R- recipients did not have
      improved adjusted survival (hazard ratio 0.82; 95% confidence interval: 0.57 to
      1.18; p = 0.30). CONCLUSIONS: Despite increased rates of PTLD and associated
      mortality in the EBV D+/R- population, EBV seronegative patients did not have
      worse mortality when transplanted with lungs from EBV seropositive donors
      compared with lungs from EBV seronegative donors. Consideration should be given
      for close monitoring for PTLD among EBV D+/R- recipients, particularly those who
      are white and less than 40 years of age.

PMID- 29223420
TI  - HER2 Confers Resistance to Foretinib Inhibition of MET-Amplified Esophageal
      Adenocarcinoma Cells.
AB  - BACKGROUND: Recent genomic studies indicated that esophageal adenocarcinoma (EAC)
      is driven by amplification of c-MET or HER2 or both in a subset of patients. We
      studied the effect of MET targeting by the small molecule inhibitor foretinib in
      EAC cells and the interplay between MET and HER2 signaling. METHODS: We measured
      the expression levels and phosphorylation status of MET and HER2 proteins in EAC
      cell lines using Western blot analysis. The expression levels of MET and HER2
      were manipulated by transfecting cells with specific siRNA or a plasmid
      expressing HER2. The small molecule inhibitors of c-MET and ERBB1/2 (foretinib
      and lapatinib, respectively) were tested for effect on growth, apoptosis, and
      downstream signaling pathways of EAC cells as single agents or in combination.
      The response to inhibitors was correlated to the levels of MET, HER2 expression,
      and amplification status. RESULTS: Foretinib inhibits phosphorylation of MET,
      which correlated with reduced EAC cell growth and inhibition of AKT and ERK
      phosphorylation. Cell growth inhibition by foretinib is most profound in the
      ESO51 cell line, which has MET gene amplification and overexpression. Inhibition
      of MET signaling by foretinib or siRNA-specific knock down of MET expression
      induces apoptosis in ESO51 cells. Ectopic expression of HER2 reduces foretinib
      mediated growth inhibition and downstream ERK phosphorylation in ESO51-HER2
      cells. The EAC OE33 cell line, with amplification and overexpression of both MET
      and HER2, demonstrated reduced sensitivity to foretinib or lapatinib and had a
      transient effect on downstream inhibition of phosphorylated AKT and ERK (p-AKT, p
      ERK). The coadministration of foretinib and lapatinib effectively blocked both
      MET and HER2 signaling through the p-AKT and p-ERK pathways, dramatically
      inhibited growth, and induced apoptosis to overcome single-agent resistance in
      OE33 cells. CONCLUSIONS: The mechanism for foretinib growth inhibition in MET
      amplified EAC tumor cells is demonstrated. The interplay of dual MET/HER2
      overexpression in the AKT and ERK pathways for esophageal cancer is described.
      Therefore, combination therapy could be a novel strategy for EAC with
      amplification of both MET and HER2.

PMID- 29223422
TI  - National Trends in the Epidemiology of Malignant Pleural Mesothelioma: A National
      Cancer Data Base Study.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) remains an aggressive malignancy
      that is difficult to cure. However, the treatment paradigm of MPM has evolved,
      and the national practice patterns are unknown. This study examined the national
      trends in the epidemiology, national treatment patterns, and survival of patients
      with this disease. METHODS: We identified all patients (n = 19,134) with MPM from
      the National Cancer Data Base from 2004 to 2013. We analyzed patient, tumor
      characteristics, and treatment patterns using descriptive statistics and used
      Kaplan-Meier and Cox proportional hazards models to estimate survival stratified
      by the type of therapy administered. RESULTS: Four histologic subtypes were
      represented in the National Cancer Data Base, these included sarcomatoid (n =
      2,355 [12.3%]), epithelioid (n = 6,858 [35.8%]), biphasic (n = 13,617 [11%]), and
      not otherwise specified (n = 8,560 [44.7%]). Across all subtypes, the prevalence
      of mesothelioma was highest among white men. Sarcomatoid had the worst survival
      (adjusted hazard ratio, 2.2; p < 0.001). Most patients did not receive any
      specific modality of treatment (40.2%). Chemotherapy alone was the most common
      treatment used (31.8%). Trimodality treatment with chemotherapy, surgical
      resection, and radiation therapy was associated with the best survival (adjusted
      hazard ratio, 0.43; p < 0.001), followed by combination chemotherapy and
      resection (adjusted hazard ratio, 0.49; p < 0.001). CONCLUSIONS: This is the
      first publication to date to analyze the mesothelioma National Cancer Data Base.
      Although survival remains poor, multimodality therapy with surgical resection is
      associated with the best survival for MPM. Further research is needed to improve
      survival and overall patient outcomes.

PMID- 29223421
TI  - A Prospective Multi-Institutional Cohort Study of Mediastinal Infections After
      Cardiac Operations.
AB  - BACKGROUND: Mediastinal infections are a potentially devastating complication of
      cardiac operations. This study analyzed the frequency, risk factors, and
      perioperative outcomes of mediastinal infections after cardiac operations.
      METHODS: In 2010, 5,158 patients enrolled in a prospective study evaluating
      infections after cardiac operations and their effect on readmissions and
      mortality for up to 65 days after the procedure. Clinical and demographic
      characteristics, operative variables, management practices, and outcomes were
      compared for patients with and without mediastinal infections, defined as deep
      sternal wound infection, myocarditis, pericarditis, or mediastinitis. RESULTS:
      There were 43 mediastinal infections in 41 patients (cumulative incidence, 0.79%;
      95% confidence interval [CI] 0.60% to 1.06%). Median time to infection was 20.0
      days, with 65% of infections occurring after the index hospitalization discharge.
      Higher body mass index (hazard ratio [HR] 1.06; 95% CI, 1.01 to 1.10), higher
      creatinine (HR, 1.25; 95% CI, 1.13 to 1.38), peripheral vascular disease (HR,
      2.47; 95% CI, 1.21 to 5.05), preoperative corticosteroid use (HR, 3.33; 95% CI,
      1.27 to 8.76), and ventricular assist device or transplant surgery (HR, 5.81; 95%
      CI, 2.36 to 14.33) were associated with increased risk of mediastinal infection.
      Postoperative hyperglycemia (HR, 3.15; 95% CI, 1.32 to 7.51) was associated with
      increased risk of infection in nondiabetic patients. Additional length of stay
      attributable to mediastinal infection was 11.5 days (bootstrap 95% CI, 1.88 to
      21.11). Readmission rates and mortality were five times higher in patients with
      mediastinal infection than in patients without mediastinal infection.
      CONCLUSIONS: Mediastinal infection after a cardiac operation is associated with
      substantial increases in length of stay, readmissions, and death. Reducing these
      infections remains a high priority, and improving post-operative glycemic
      management may reduce their risk in patients without diabetes.

PMID- 29223423
TI  - The Requirement of Sutures to Close Intercostal Drains Site Wounds in Thoracic
      Surgery.
AB  - BACKGROUND: Chest drains are used routinely in thoracic surgery. Often a
      pursestring or mattress suture is used to facilitate closure of the defect on
      removal of the drain. This stitch can cause an unsightly scar, increase drain
      removal pain, and necessitate that the patient attend a community health care
      center to have this removed. The objective of this study was to assess whether
      this stitch is necessary in modern thoracic surgical practice. METHODS: Data from
      a single surgeon's practice were collected over an 18-month period. During this
      time, all patients who underwent both emergency and elective thoracic surgery who
      had at least one postoperative chest drain of 28F or above inserted were included
      in the study. The surgeon did not routinely use a suture to close the drain site.
      RESULTS: In all, 312 patients underwent thoracic surgery during the 18-month
      period. Each patient had a range of 1 to 3 drains inserted of a size between 28F
      and 32F. No patients had drain sutures for closure of the drain site. Four
      patients had pneumothoraces after drain removal requiring further chest drain
      insertion. Five patients had superficial drain site infections. A single patient
      had to have a suture inserted at a local hospital owing to leakage from the drain
      site. CONCLUSIONS: The use of pursestring sutures in thoracic surgery is an
      outdated practice that causes not only unsightly scars but is also associated
      with increased pain. Furthermore, these unnecessary pursestring sutures place a
      burden on the patient and health care system to have them removed.

PMID- 29223424
TI  - Outcome After Lung Volume Reduction Surgery in Patients With Severely Impaired
      Diffusion Capacity.
AB  - BACKGROUND: Lung volume reduction surgery (LVRS) has been proven to be a
      successful procedure and can be performed with low mortality when defined
      selection criteria are met. We hypothesized good outcome and low mortality after
      LVRS for selected patients with severe hyperinflation and nonhomogeneous
      morphology even when diffusion capacity of the lung for carbon monoxide (Dlco) is
      less than 20%. METHODS: The study included all patients scheduled for LVRS
      between March 2005 and May 2014 with a preoperative Dlco of less than 20%.
      Postoperative 90-day mortality was the primary end point. Secondary end points
      were postoperative lung function and surgical morbidity at 3, 6, and 12 months.
      RESULTS: Included were 33 patients with a median forced expiratory volume in 1
      second of 23% (interquartile range, 19% to 28%), a median diffusion capacity of
      15% (interquartile range, 13% to 18%), and a median hyperinflation of 76%
      (residual volume-to-total lung capacity ratio of 70% to 76%). Mean follow-up was
      44.8 months (range, 10 to 141 months). Heterogeneous emphysema was present in 26
      patients, and 7 showed intermediately heterogeneous morphology. Sixteen
      procedures were bilateral, and 31 were performed by video-assisted thoracoscopic
      surgery. The 90-day mortality was 0%. Median forced expiratory volume in 1 second
      percentage predicted at 3 months increased from 23% to 29% (p < 0.001). Median
      Dlco increased from 15% to 24% (p < 0.001), and median hyperinflation decreased
      from 76% to 63% (p < 0.001). A prolonged air leak exceeding 7 days occurred in 16
      patients (48.5%), and 6 required reoperation for fistula closure. The 7 patients
      with intermediately heterogeneous emphysema showed a median increase in forced
      expiratory volume in 1 second from 20% preoperatively to 28% postoperatively (p =
      0.028). CONCLUSIONS: Selected patients with severely impaired Dlco of less than
      20% can cautiously be considered as potential candidates if hyperinflation is
      severe and the lungs show areas with advanced destruction as targets for
      resection.

PMID- 29223425
TI  - Assessing age-dependent multi-task functional co-activation changes using
      measures of task-potency.
AB  - It is being hypothesised that the developing adolescent brain is increasingly
      enlisting long-range connectivity, allowing improved communication between
      spatially distant brain regions. The developmental trajectories of such
      maturational changes remain elusive. Here, we aim to study how the brain engages
      in multiple tasks (working memory, reward processing, and inhibition) at the
      network-level and evaluate how effects of age across these tasks are related to
      each other. We characterise how the brain departs from its functional baseline
      architecture towards task-induced functional connectivity modulations using a
      novel measure called task potency, allowing direct comparison between tasks by
      defining sensitivity to one or multiple tasks. By applying this method in a
      sample of healthy participants (N = 218) aged 8-30 years, we demonstrate
      maturational changes in task-dependent functional co-activation over and above
      baseline connectivity maturation. Our results provide evidence for task-specific
      maturational windows with different cognitive systems probed by different tasks
      displaying specific age-range dependencies of strongest developmental change. Our
      results highlight the use of task potency for modelling developmental
      trajectories and the impact of differential maturation across tasks. This enables
      better characterisation of cognitive processes disrupted in neurodevelopmental
      disorders and may explain the increased level of heterogeneity observed in
      adolescent population studies.

PMID- 29223426
TI  - Application of solidifiers for oil spill containment: A review.
AB  - The need for new and/or improvement of existing oil spill remediation measures
      has increased substantially amidst growing public concern with the increased
      transportation of unconventional crudes, such as diluted bitumen products.
      Solidifiers may be a very good spill response measure to contain and mitigate the
      effects of oil discharge incidents, as these interact with the oil to limit
      hydrocarbon release into air and water, prevent it from adhering onto sediment
      and debris, and could allow for oil recovery and reuse. Solidifiers change the
      physical state of the spilled oil from liquid to a coherent mass by chemical
      interactions between the spilled oil and the solidifier. Currently, the use of
      solidifiers is limited to small spills near shorelines. To extend their use to
      large-scale spill containment operations, it is necessary to understand the
      mechanism of solidifier action and to establish consistent criteria for
      evaluation of their effectiveness. The research effort to date has been focused
      mainly on gelators and cross-linking agents, with particularly impressive
      advancements in the areas of phase-selective polymeric and small-molecule
      gelators. Substantial research efforts are needed to improve solidifier
      performance and integrate solidifiers as part of spill response procedures,
      particularly for acute oil spills involving unconventional petroleum products.

PMID- 29223427
TI  - Late outcome of percutaneous mitral commissurotomy: Randomized comparison of
      Inoue versus double-balloon technique.
AB  - BACKGROUND: Late prognosis after successful percutaneous mitral commissurotomy
      (PMC) is unclear. We compared late results of PMC using Inoue versus double
      balloon techniques up to 25 years in a randomized trial. METHODS: Between 1989
      and 1995, 302 patients (77 men, 41 +/- 11 years) with severe mitral stenosis were
      randomly assigned to undergo PMC using Inoue (n = 152; group I) or double-balloon
      technique (n = 150; group D). The end points were the composite events of death,
      mitral surgery, repeat PMC, or deterioration of New York Heart Association (NYHA)
      class >=3. RESULTS: During median follow-up of 20.7 years (maximum, 25.6),
      clinical events occurred in 82 (53.9%) patients in group I (37 deaths, 44 mitral
      surgeries, 9 repeat PMCs, 3 NYHA class >=3) and in 79 (52.7%) patients in group D
      (34 deaths, 51 mitral surgeries, 5 repeat PMCs, 4 NYHA class >=3). Event-free
      survival rates at 24 years were not significantly different between group I and
      group D (40.8% and 42.6%, respectively; hazard ratio [HR], 0.88; 95% confidence
      interval [CI], 0.65-1.20; P = .423). On multivariate analysis, absence of post
      PMC commissural mitral regurgitation (MR) (HR, 1.84; 95% CI, 1.28-2.63; P = .001)
      and immediate post-PMC mitral valve area (MVA) <1.8 cm2 (HR, 1.53; 95% CI, 1.04
      2.25; P = .031) were independently correlated with clinical events after
      successful PMC. CONCLUSIONS: The Inoue and double-balloon methods showed similar
      good clinical outcomes up to 25 years, and the achievement of effective
      commissurotomy to develop post-PMC commissural MR or immediate post-PMC MVA >=1.8
      cm2 is important in optimizing the late results of PMC.

PMID- 29223428
TI  - Enabling social listening for cardiac safety monitoring: Proceedings from a drug
      information association-cardiac safety research consortium cosponsored think
      tank.
AB  - This white paper provides a summary of the presentations and discussions from a
      think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials
      that was cosponsored by the Drug Information Association and the Cardiac Safety
      Research Consortium, and held at the White Oak headquarters of the US Food and
      Drug Administration on June 3, 2016. The meeting's goals were to explore current
      methods of collecting and evaluating social listening data and to consider their
      applicability to cardiac safety surveillance. Social listening is defined as the
      act of monitoring public postings on the Internet. It has several theoretical
      advantages for drug and device safety. First, these include the ability to detect
      adverse events that are "missed" by traditional sources and the ability to detect
      adverse events sooner than would be allowed by traditional sources, both by
      affording near-real-time access to data from culturally and geographically
      diverse sources. Social listening can also potentially introduce a novel patient
      voice into the conversation about drug safety, which could uniquely augment
      understanding of real-world medication use obtained from more traditional
      methodologies. Finally, it can allow for access to information about drug misuse
      and diversion. To date, the latter 2 of these have been realized. Although
      regulators from the Food and Drug Administration and the United Kingdom's
      Medicines and Healthcare Products Regulatory Agency participated in the think
      tank along with representatives from industry, academia, and patient groups, this
      article should not be construed to constitute regulatory guidance.

PMID- 29223429
TI  - Predicting risk of cardiac events among ST-segment elevation myocardial
      infarction patients with conservatively managed non-infarct-related artery
      coronary artery disease: An analysis of the Duke Databank for Cardiovascular
      Disease.
AB  - BACKGROUND: Recent randomized evidence has demonstrated benefit with complete
      revascularization during the index hospitalization for multivessel coronary
      artery disease ST-segment elevation myocardial infarction (STEMI) patients;
      however, this benefit likely depends on the risk of future major adverse
      cardiovascular events (MACE). METHODS: Using data from Duke University Medical
      Center (2003-2012), we identified those at high risk for 1-year MACE among 664
      STEMI patients with conservatively managed non-infarct-related artery (non-IRA)
      lesions. Using multivariable logistic regression, we identified clinical and
      angiographic characteristics associated with MACE (death, myocardial infarction,
      urgent revascularization) to 1 year and developed an integer-based risk
      prediction model for clinical use. RESULTS: In this cohort (median age 60 years,
      30% female), the unadjusted Kaplan-Meier rates for MACE at 30 days and 1 year
      were 10% and 28%, respectively. Characteristics associated with MACE at 1 year
      included reduced left ventricular ejection fraction, hypertension, heart failure,
      higher-risk non-IRA vessels (left main), renal insufficiency, and greater %
      stenosis of non-IRA lesions. A 15-point risk score including these variables had
      modest discrimination (C-index 0.67) across a spectrum of subsequent risk (4%
      88%) for 1-year MACE. CONCLUSIONS: There is a wide spectrum of risk following
      primary percutaneous coronary intervention for STEMI patients with multivessel
      disease. Using readily available clinical characteristics, the expected incidence
      of MACE by 1 year can be calculated with a simplified risk score, facilitating a
      tailored approach to clinical care.

PMID- 29223430
TI  - Rational and design of a randomized, double-blind, multicenter trial to evaluate
      the safety and tolerability of furosemide withdrawal in stable chronic
      outpatients with heart failure: The ReBIC-1 trial.
AB  - AIMS: Furosemide is commonly prescribed for symptom relief in heart failure (HF)
      patients. Although few data support the continuous use of loop diuretics in
      apparently euvolemic HF patients with mild symptoms, there is concern about
      safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed
      to evaluate the safety and tolerability of withdrawing furosemide in stable,
      euvolemic, chronic HF outpatients. This multicenter initiative is part of the
      Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical
      studies in HF and composed predominantly by university tertiary care hospitals.
      METHODS: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional
      class I-II, left ventricular ejection fraction <=45%, without a HF-related
      hospital admission within the last 6 months, receiving a stable dose of
      furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be
      randomized to maintain or withdraw furosemide in a double-blinded protocol. The
      trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue
      scale evaluated at 4 time points and (2) the proportion of patients maintained
      without diuretics during the follow-up period. Total sample size was calculated
      to be 220 patients. Enrolled patients will be followed up to 90 days after
      randomization, and diuretic will be restarted if clinical deterioration or signs
      of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP
      levels at baseline is planned. PERSPECTIVE: Evidence-based strategies aiming to
      simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial
      will determine the safety of withdrawing furosemide in stable chronic HF
      patients.

PMID- 29223431
TI  - International trends in clinical characteristics and oral anticoagulation
      treatment for patients with atrial fibrillation: Results from the GARFIELD-AF,
      ORBIT-AF I, and ORBIT-AF II registries.
AB  - : Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We
      aimed to provide comprehensive data on international patterns of AF stroke
      prevention treatment. METHODS: Demographics, comorbidities, and stroke risk of
      the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF
      II (n=11,602) registries were compared (overall N=73,004 from 35 countries).
      Stroke prevention therapies were assessed among patients with new-onset AF (<=6
      weeks). RESULTS: Patients from GARFIELD-AF were less likely to be white (63% vs
      89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19%
      vs 36% and 27%), but had similar stroke risk (85% CHA2DS2-VASc >=2 vs 91% and
      85%) and lower bleeding risk (11% with HAS-BLED >=3 vs 24% and 15%). Oral
      anticoagulant use was 46% and 57% for patients with a CHA2DS2-VASc=0 and 69% and
      87% for CHA2DS2-VASc >=2 in GARFIELD-AF and ORBIT-AF II, respectively, but with
      substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93%
      [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non
      vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016
      for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy
      decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II).
      CONCLUSIONS: Among new-onset AF patients, non-vitamin K antagonist oral
      anticoagulant use has increased and antiplatelet monotherapy has decreased.
      However, anticoagulation is used frequently in low-risk patients and
      inconsistently in those at high risk of stroke. Significant geographic
      variability in anticoagulation persists and represents an opportunity for
      improvement.

PMID- 29223432
TI  - Contemporary risk model for inhospital major bleeding for patients with acute
      myocardial infarction: The acute coronary treatment and intervention outcomes
      network (ACTION) registry(r)-Get With The Guidelines (GWTG)(r).
AB  - BACKGROUND: Major bleeding is a frequent complication for patients with acute
      myocardial infarction (AMI) and is associated with significant morbidity and
      mortality. OBJECTIVE: To develop a contemporary model for inhospital major
      bleeding that can both support clinical decision-making and serve as a foundation
      for assessing hospital quality. METHODS: An inhospital major bleeding model was
      developed using the Acute Coronary Treatment and Intervention Outcomes Network
      Registry-Get With the Guidelines (ACTION Registry-GWTG) database. Patients
      hospitalized with AMI between January 1, 2012 and December 31, 2013 across 657
      hospitals were used to create a derivation cohort (n=144,800) and a validation
      cohort (n=96,684). Multivariable hierarchal logistic regression was used to
      identify significant predictors of major bleeding. A simplified risk score was
      created to enable prospective risk stratification for clinical care. RESULTS: The
      rate of major bleeding in the overall population was 7.53%. There were 8
      significant, independent factors associated with major bleeding: presentation
      after cardiac arrest (OR 2.99 [2.77-3.22]); presentation in cardiogenic shock (OR
      2.22 [2.05-2.40]); STEMI (OR 1.72 [1.65-1.80]); presentation in heart failure (OR
      1.55 [1.47-1.63]); baseline hemoglobin less than 12 g/dL (1.55 [1.48-1.63]);
      heart rate (per 10 beat per minute increase) (OR 1.13 [1.12-1.14]); weight (per
      10 kilogram decrease) (OR 1.12 [1.11-1.14]); creatinine clearance (per 5-mL
      decrease) (OR 1.07 [1.07-1.08]). The model discriminated well in the derivation
      (C-statistic = 0.74) and validation (C-statistic = 0.74) cohorts. In the
      validation cohort, a risk score for major bleeding corresponded well with
      observed bleeding: very low risk (2.2%), low risk (5.1%), moderate risk (10.1%),
      high risk (16.3%), and very high risk (25.2%). CONCLUSION: The new ACTION
      Registry-GWTG inhospital major bleeding risk model and risk score offer a robust,
      parsimonious, and contemporary risk-adjustment method to support clinical
      decision-making and enable hospital quality assessment. Strategies to mitigate
      risk should be developed and tested as a means to lower costs and improve
      outcomes in an era of alternative payment models.

PMID- 29223433
TI  - Contemporary rates and correlates of statin use and adherence in nondiabetic
      adults with cardiovascular risk factors: The KP CHAMP study.
AB  - BACKGROUND: Statin therapy is highly efficacious in the prevention of fatal and
      nonfatal atherosclerotic events in persons at increased cardiovascular risk.
      However, its long-term effectiveness in practice depends on a high level of
      medication adherence by patients. METHODS: We identified nondiabetic adults with
      cardiovascular risk factors between 2008 and 2010 within a large integrated
      health care delivery system in Northern California. Through 2013, we examined the
      use and adherence of newly initiated statin therapy based on data from dispensed
      prescriptions from outpatient pharmacy databases. RESULTS: Among 209,704 eligible
      adults, 68,085 (32.5%) initiated statin therapy during the follow-up period, with
      90.4% receiving low-potency statins. At 12 and 24 months after initiating
      statins, 84.3% and 80.2%, respectively, were actively receiving statin therapy,
      but only 42% and 30%, respectively, had no gaps in treatment during those time
      periods. There was also minimal switching between statins or use of other lipid
      lowering therapies for augmentation during follow-up. Age>=50 years,
      Asian/Pacific Islander race, Hispanic ethnicity, prior myocardial infarction,
      prior ischemic stroke, hypertension, and baseline low-density lipoprotein
      cholesterol>100 mg/dL were associated with higher adjusted odds, whereas female
      gender, black race, current smoking, dementia were associated with lower adjusted
      odds, of active statin treatment at 12 months after initiation. CONCLUSIONS:
      There remain opportunities for improving prevention in patients at risk for
      cardiovascular events. Our study identified certain patient subgroups that may
      benefit from interventions to enhance medication adherence, particularly by
      minimizing treatment gaps and discontinuation of statin therapy within the first
      year of treatment.

PMID- 29223434
TI  - Durability of quality of life benefits of transcatheter aortic valve replacement:
      Long-term results from the CoreValve US extreme risk trial.
AB  - BACKGROUND: For patients with severe aortic stenosis (AS) at extreme surgical
      risk, transcatheter aortic valve replacement (TAVR) leads to improved survival
      and health status when compared with medical therapy. Whether the early health
      status benefits of TAVR in these patients are sustained beyond 1 year of follow
      up is unknown. METHODS AND RESULTS: Six hundred thirty-nine patients with severe
      AS at extreme surgical risk underwent TAVR in the CoreValve US Extreme Risk
      Pivotal trial. Health status was evaluated at baseline and at 1, 6, 12, 24, and
      36 months using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Short
      Form-12, and the EuroQoL-5D. Analyses were performed using pattern mixture models
      to account for both death and missing data and were stratified by iliofemoral
      (IF) and non-iliofemoral (non-IF) access. After TAVR, there was substantial
      health status improvement in disease-specific and generic scales by 6 to 12
      months. Although there were small declines in health status after 12 months, the
      initial benefits of TAVR were largely sustained through 3 years for both IF and
      non-IF cohorts (change from baseline in KCCQ Overall Summary score 19.0 points in
      IF patients and 14.9 points in non-IF patients; P<.01 for both comparisons).
      Among surviving patients, clinically meaningful (>=10 point) improvements in the
      KCCQ Overall Summary Score at 3 years were observed in 85.0% and 83.4% of IF and
      non-IF patients respectively. CONCLUSIONS: Among extreme risk patients with
      severe AS, TAVR resulted in large initial health status benefits that were
      sustained through 3-year follow-up. Although late mortality was high in this
      population, these findings demonstrate that TAVR offers substantial and durable
      health status improvements for surviving patients.

PMID- 29223436
TI  - Predictors of high cost after percutaneous coronary intervention: A review from
      Japanese multicenter registry overviewing the influence of procedural
      complications.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is widely used; however,
      factors of high-cost care after PCI have not been thoroughly investigated. We
      sought to evaluate the in-hospital costs related to PCI and identify predictors
      of high costs. METHODS: We extracted 2,354 consecutive PCI cases (1,243 acute
      cases, 52.8%) from 3 Japanese cardiovascular centers from 2011 to 2015. In
      hospital complications were predefined under consensus definitions (eg, acute
      kidney injury [AKI]). We extracted the facility cost data for each patient's
      resource under the universal Japanese insurance system. We classified the
      patients into total cost quartiles and identified predictors for the highest
      quartile ("high-cost" group). In addition, incremental costs for procedure
      related complications were calculated. RESULTS: During the study period, a total
      of 401 cases (17.0%) experienced procedure-related complications. The in-hospital
      acute and elective PCI costs per case were US $14,840 (interquartile range [IQR]
      11,370-20,070) and US $11,030 (IQR 8929-14,670), respectively. After adjusting
      for baseline differences, any of the procedure-related complications remained an
      independent predictor of high costs (acute: odds ratio 1.66, 95% CIs 1.13-2.43;
      elective: odds ratio 3.73, 95% CIs 1.96-7.11). Notably, incremental costs were
      mainly attributed to AKI, which accounted for 37.5% of all incremental costs; it
      increased by US $9,840 for each AKI event, and the total cost increase reached US
      $2,588,035. CONCLUSIONS: Procedure-related complications, particularly
      postprocedural AKI, were associated with higher costs in PCI. Further studies are
      required to evaluate prospectively whether the preventive strategy with a
      personalized risk stratification for AKI could save costs.

PMID- 29223435
TI  - Atrial fibrillation decision support tool: Population perspective.
AB  - BACKGROUND: Appropriate thromboprophylaxis for patients with atrial fibrillation
      or atrial flutter (AF) remains a national challenge. The recent availability of
      direct oral anticoagulants (DOACs) with comparable efficacy and improved safety
      compared with warfarin alters the balance between risk factors for stroke and
      benefit of anticoagulation. Our objective was to examine the impact of DOACs as
      an alternative to warfarin on the net benefit of oral anticoagulant therapy (OAT)
      in a real-world population of AF patients. METHODS: This is a retrospective
      cohort study of patients with paroxysmal or persistent nonvalvular AF. We updated
      an Atrial Fibrillation Decision Support Tool (AFDST) to include DOACs as
      treatment options. The tool generates patient-specific recommendations based upon
      individual patient risk factor profiles for stroke and major bleeding using
      quality-adjusted life-years (QALYs) calculated for each treatment strategy by a
      decision analytic model. The setting included inpatient and ambulatory sites in
      an academic health center in the midwestern United States. The study involved
      5,121 adults with nonvalvular AF seen for any ambulatory visit or inpatient
      hospitalization over the 1-year period (January through December 2016). Outcome
      measure was net clinical benefit in QALYs. RESULTS: When DOACs are a therapeutic
      option, the AFDST recommends OAT for 4,134 (81%) patients and no antithrombotic
      therapy or aspirin for 489 (9%). A strong recommendation for OAT could not be
      made in 498 (10%) patients. When warfarin is the only option, OAT is recommended
      for 3,228 (63%) patients and no antithrombotic therapy or aspirin for 973 (19%).
      A strong recommendation for OAT could not be made in 920 (18%) patients. In
      total, 1,508 QALYs could be gained if treatment were changed to that recommended
      by the AFDST. CONCLUSIONS: Availability of DOACs increases the proportion of
      patients for whom oral anticoagulation therapy is recommended in a real-world
      cohort of AF patients and increased projected QALYs by more than 1,500 when all
      patients are receiving thromboprophylaxis as recommended by the AFDST compared
      with current treatment.

PMID- 29223437
TI  - Outcomes in elderly and young patients with ST-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention with bivalirudin
      versus heparin: Pooled analysis from the EUROMAX and HORIZONS-AMI trials.
AB  - BACKGROUND: Since older age is a strong predictor of not only bleeding but also
      of ischemic events, understanding the risk:benefit profile of bivalirudin in the
      elderly undergoing primary percutaneous coronary intervention (pPCI) for ST
      segment elevation (STEMI) is important. For this, we aim to compare elderly with
      young patients, who all underwent pPCI for STEMI and randomly received either
      bivalirudin or heparin. METHODS: We performed a patient-level pooled analysis
      (n=5800) of two large randomized trials. A total of 2149 (37.1%) elderly patients
      (>65 years of age) with STEMI were enrolled and randomly assigned to either
      bivalirudin or heparin with or without a GPI (control group) before pPCI.
      Clinical outcomes at 30 days were analyzed. RESULTS: In elderly patients,
      bivalirudin significantly reduced non-CABG major bleeding (7.1% vs 10.4%; P<.01),
      subacute ST (0.4% vs 1.5%; P<.01), and net adverse clinical events (NACE;
      composite of all-cause mortality, reinfarction, IDR, stroke or protocol-defined
      non-CABG major bleeding [13.7% vs 17.2%; P=.03]) with comparable rates of stroke,
      MI, acute ST, or all-cause death, when compared with heparin with or without GPI.
      CONCLUSIONS: In a large group of elderly patients enrolled in the EUROMAX and
      HORIZONS-AMI trials, bivalirudin was associated with lower 30-day rates of non
      CABG major bleeding, subacute ST and NACE, with similar 30-day rates of acute ST
      and mortality.

PMID- 29223438
TI  - "Bringing on the light" in a complex clinical scenario: Optical coherence
      tomography-guided discontinuation of antiplatelet therapy in cancer patients with
      coronary artery disease (PROTECT-OCT registry).
AB  - BACKGROUND: Cancer patients with recently placed drug-eluting stents (DESs) often
      require premature dual antiplatelet therapy (DAPT) discontinuation for cancer
      related procedures. Optical coherence tomography (OCT) can identify risk factors
      for stent thrombosis such as stent malapposition, incomplete strut coverage and
      in-stent restenosis and may help guide discontinuation of DAPT. METHODS: We
      conducted a single-center prospective study in cancer patients with recently
      placed (1-12 months) DES who required premature DAPT discontinuation. Patients
      were evaluated with diagnostic coronary angiogram and OCT. Individuals with
      appropriate stent strut coverage, expansion, apposition, and absence of in-stent
      restenosis or intraluminal masses were considered low risk and transiently
      discontinued DAPT to allow optimal cancer therapy. Patients who did not meet all
      these criteria were considered high risk and underwent further endovascular
      treatment when appropriate and bridging with low-molecular weight heparin. The
      incidence of adverse cardiovascular events was assessed after the procedure and
      at 12 months. RESULTS: A total of 40 patients were included. Twenty-seven
      patients (68%) were considered low risk by OCT criteria and DAPT was transiently
      discontinued. Thirteen patients (32%) were considered high risk with one or more
      OCT findings: uncovered stent struts (4 patients, 10%); stent underexpansion (3
      patients, 8%); malapposition (8 patients, 20%); in-stent restenosis (2 patients,
      5%). The high-risk patients with uncovered stent struts and malapposition
      underwent additional stent dilatation. There were no cardiovascular events in the
      low-risk group. One myocardial infarction occurred in the high-risk group.
      Fourteen non-cardiac deaths were registered before 12 months due to cancer
      progression or cancer therapy. CONCLUSION: OCT imaging allows identification of
      low-risk cancer patients with DES placed who may safely discontinue DAPT and
      proceed with cancer-related surgery or procedures.

PMID- 29223439
TI  - A unique linkage of administrative and clinical registry databases to expand
      analytic possibilities in pediatric heart transplantation research.
AB  - BACKGROUND: Large clinical, research, and administrative databases are
      increasingly utilized to facilitate pediatric heart transplant (HTx) research.
      Linking databases has proven to be a robust strategy across multiple disciplines
      to expand the possible analyses that can be performed while leveraging the
      strengths of each dataset. We describe a unique linkage of the Scientific
      Registry of Transplant Recipients (SRTR) database and the Pediatric Health
      Information System (PHIS) administrative database to provide a platform to assess
      resource utilization in pediatric HTx. METHODS: All pediatric patients (1999
      2016) who underwent HTx at a hospital enrolled in the PHIS database were
      identified. A linkage was performed between the SRTR and PHIS databases in a
      stepwise approach using indirect identifiers. To determine the feasibility of
      using these linked data to assess resource utilization, total and post-HTx
      hospital costs were assessed. RESULTS: A total of 3188 unique transplants were
      identified as being present in both databases and amenable to linkage. Linkage of
      SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%)
      had complete cost data. Median total and post-HTx hospital costs were $518,906
      (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with
      significant differences based on patient demographics and clinical
      characteristics at HTx. CONCLUSIONS: Linkage of the SRTR and PHIS databases is
      feasible and provides an invaluable tool to assess resource utilization. Our
      analysis provides contemporary cost data for pediatric HTx from the largest US
      sample reported to date. It also provides a platform for expanded analyses in the
      pediatric HTx population.

PMID- 29223440
TI  - Outcomes of cardiac pacing in adult patients after a Fontan operation.
AB  - BACKGROUND: Cardiac pacing can be challenging after a Fontan operation, and
      limited data exist regarding pacing in adult Fontan patients. The objectives of
      our study were to determine risk factors for pacing and occurrence of device
      related complications (DRCs) and pacemaker reinterventions. METHODS: We performed
      a retrospective review of Fontan patients from 1994 through 2014. We defined DRCs
      as lead failure, lead recall, cardiac perforation, lead thrombus/vegetation, or
      device-related infection, and cardiovascular adverse events (CAEs) as venous
      thrombosis, stroke, death, or heart transplant. Pacemaker reintervention was
      defined as lead failure or recall. RESULTS: Of 439 patients, 166 (38%) had
      pacemakers implanted (79 during childhood; 87, adulthood); 114 patients (69%)
      received epicardial leads initially, and 52 (31%), endocardial leads. Pacing was
      initially atrial in 52 patients (31%); ventricular, 30 (18%); or dual chamber, 84
      (51%). There were 37 reinterventions (1.9% per year) and 48 DRCs (2.4% per year).
      Pacemaker implantation during childhood was a risk factor for DRCs (hazard ratio,
      2.01 [CI, 1.22-5.63]; P = .03). There were 70 CAEs (venous thrombosis, 5; stroke,
      11; transplant, 8; and death, 46), yielding a rate of 3.5% per year. DRCs, CAEs,
      and reintervention rates were comparable for patients with epicardial or
      endocardial leads. CONCLUSIONS: More than one-third of adult Fontan patients
      referred to Mayo Clinic had pacemaker implantation. Epicardial leads were
      associated with high rate of pacemaker reinterventions but similar DRC rates in
      comparison to endocardial leads.

PMID- 29223441
TI  - Edoxaban for the management of elderly Japanese patients with atrial fibrillation
      ineligible for standard oral anticoagulant therapies: Rationale and design of the
      ELDERCARE-AF study.
AB  - Edoxaban-a non-vitamin K antagonist oral anticoagulant (NOAC)- 60-mg and 30-mg
      once-daily dose regimens are noninferior versus well-managed warfarin for the
      prevention of stroke or systemic embolic events (SEE) with less major bleeding in
      patients with nonvalvular atrial fibrillation (NVAF). There are no published data
      from phase 3 clinical trials specifically evaluating the use of NOACs in elderly
      NVAF patients, especially those considered ineligible for available oral
      anticoagulants. The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF)
      study is a phase 3, randomized, double-blind, placebo-controlled, parallel-group,
      multicenter study that will compare the safety and efficacy of once-daily
      edoxaban 15 mg versus placebo in Japanese patients with NVAF >=80 years of age
      who are considered ineligible for standard oral anticoagulant therapy. A total of
      800 patients (400 in each treatment group) are planned for randomization (1:1) to
      either edoxaban or placebo using a stratified randomization method with CHADS2
      index score (2 points, >=3 points) as a factor. The primary efficacy end point is
      the time to first onset of stroke or SEE. The net clinical outcome is the
      composite of stroke, SEE, major bleeding, and all-cause mortality. The primary
      safety end point is the incidence of major bleeding. The treatment period will
      continue until 65 patients with the primary efficacy events (ie, stroke or SEE)
      have been observed (2- to 2.5-year expected mean treatment period). The results
      of ELDERCARE-AF may provide clarity as to the efficacy and safety of edoxaban for
      the prevention of stroke or SEE in this high-risk population.

PMID- 29223442
TI  - Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a
      horizontal transfer of drug-resistant trait by delivering miR-365.
AB  - Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic
      stem/progenitor cells. Majority of patients can be effectively treated with
      tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients
      will develop drug resistance. Accumulated evidences have identified exosomes in
      cancer as promoters of tumor progression. Herein, we found that exosomes derived
      from imatinib resistant CML cells can be internalized into sensitive CML cells
      and confer drug-resistance traits. We also demonstrated a significant higher
      level of miR-365 in exosomes derived from drug-resistant CML cells compared with
      those from sensitive ones using microarray and qRT-PCR. The imatinib sensitive
      CML cells transfected with pre-miR-365 displayed lower chemosensitivity and
      apoptosis rate compared with controls. We further confirmed that exosomal
      transfer of miR-365 induced drug resistance by inhibiting expression of pro
      apoptosis protein in sensitive CML cells. In conclusion, our study reveals that
      exosomes mediate a horizontal transfer of drug-resistant trait in chronic myeloid
      leukemia cell by delivering miR-365.

PMID- 29223443
TI  - Response to Pioglitazone in Patients With Nonalcoholic Steatohepatitis With vs
      Without Type 2 Diabetes.
AB  - BACKGROUND & AIMS: Pioglitazone is effective for long-term treatment of patients
      with nonalcoholic steatohepatitis (NASH) with prediabetes or type 2 diabetes.
      However, it is not clear how the presence of type 2 diabetes affects the drug's
      efficacy. We compared metabolic and histologic responses to pioglitazone in
      patients with NASH and prediabetes vs type 2 diabetes. METHODS: We performed a
      prospective study of adults with biopsy-proven NASH (52 with type 2 diabetes and
      49 with prediabetes), enrolled from the general population of San Antonio, Texas,
      from 2008 through 2014. After a run-in period of approximately 4 weeks, when all
      baseline measurements were made (liver magnetic resonance proton spectroscopy,
      euglycemic insulin clamp with glucose turnover measurements, dual-energy
      absorptiometry, and liver biopsy), subjects were randomly assigned to groups
      given pioglitazone or placebo (45 mg/d) for 18 months; all procedures performed
      at baseline were then repeated. The primary outcome was a reduction in
      nonalcoholic fatty liver disease activity score of 2 points or more (for at least
      2 components) without worsening of fibrosis (and expressed as difference vs
      placebo). Secondary outcomes included NASH resolution, individual histologic
      components, intrahepatic triglyceride content (measured by 1H magnetic resonance
      spectroscopy), and insulin sensitivity (measured by euglycemic insulin clamp).
      RESULTS: The primary outcome was met by 48% of patients with type 2 diabetes vs
      46% without diabetes. Resolution of NASH was achieved in 44% of patients with
      type 2 diabetes vs 26% without diabetes. A significant reduction in fibrosis,
      from baseline, was observed only in patients with type 2 diabetes (P = .035).
      Intrahepatic triglyceride content was reduced by 11% +/- 2% in patients with
      diabetes vs a reduction of 9% +/- 2% in patients without diabetes (P = .62); the
      plasma level of alanine aminotransferase was reduced by 50 +/- 10 U/L in patients
      with diabetes vs a reduction of 36 +/- 5 U/L in patients without diabetes (P =
      .22). Pioglitazone was associated with a significantly greater insulin
      sensitivity in adipose tissue of patients with diabetes vs without diabetes (P <
      .001), but nonsignificant differences in responses in hepatic (P = .49) and
      skeletal muscle (P = .32) insulin sensitivity. CONCLUSIONS: In a prospective
      study, we found pioglitazone to be effective in patients with and without type 2
      diabetes. However, pioglitazone reduced liver fibrosis and increased adipose
      tissue insulin sensitivity at significantly greater levels in patients with type
      2 diabetes than in patients with prediabetes. Further studies are needed to
      determine the mechanisms by which pioglitazone reduces liver disease in patients
      with type 2 diabetes. ClinicalTrials.gov: NCT00994682.

PMID- 29223444
TI  - Association of Vedolizumab Level, Anti-Drug Antibodies, and alpha4beta7 Occupancy
      With Response in Patients With Inflammatory Bowel Diseases.
AB  - BACKGROUND & AIMS: There are few data available on the real-life pharmacokinetic
      and pharmacodynamics features of vedolizumab, a monoclonal antibody against
      integrin alpha4beta7. We performed a prospective study of patients with
      inflammatory bowel diseases (IBDs) treated with vedolizumab to determine serum
      drug concentrations, formation of antivedolizumab antibodies (AVAs), and integrin
      alpha4beta7 saturation. METHODS: We performed a prospective study of 106 patients
      with IBD (67 with Crohn's disease and 39 with ulcerative colitis) treated with
      vedolizumab from September 2014 through March 2017 at 2 tertiary medical centers
      in Israel. Clinical data and serum samples were collected before and during
      induction and maintenance therapy. Clinical remission was defined as Harvey
      Bradshaw index scores below 5 or as Simple Clinical Colitis Activity Index scores
      of 3 or less. We measured serum levels of vedolizumab, AVAs, and markers of
      inflammation. Peripheral blood mononuclear cells were obtained from some patients
      at designated trough time points and CD3+ CD45RO+ T cells were isolated from 36
      samples. Cells were incubated with fluorescent-conjugated vedolizumab and flow
      cytometry was used to quantify alpha4beta7 integrin saturation. We also performed
      flow cytometry analyses of CD3+ CD45RO+ lamina propria T cells isolated from
      intestinal mucosa of patients without IBD (non-IBD controls, n = 6), patients
      with IBD not treated with vedolizumab (untreated IBD controls, n = 8), and
      patients with IBD treated with vedolizumab (n = 15). RESULTS: Clinical remission
      was achieved by 48 of 106 patients (45%) by week 6 and 50 of 106 patients (48%)
      by week 14 of treatment. The median level of vedolizumab at week 6 was higher in
      patients in clinical remission (40.2 MUg/mL) than in patients with active disease
      (29.7 MUg/mL; P = .05). The median serum level of vedolizumab was significantly
      higher in patients with a normal level of C-reactive protein (21.8 MUg/mL
      vedolizumab) vs the level in those with a high level of C-reactive protein (11.9
      MUg/mL vedolizumab) during maintenance treatment (P = .0006). The other clinical
      outcomes measured were not associated with median serum level of vedolizumab at
      any time point examined. AVAs were detected in 17% of patients during induction
      therapy and 3% of patients during maintenance therapy, but did not correlate with
      clinical outcomes. Flow-cytometry analysis of peripheral blood memory T cells (n
      = 36) showed near-complete occupancy of alpha4beta7 integrin at weeks 2 and 14
      and during the maintenance phase, regardless of response status or drug levels.
      Most intestinal CD3+CD45RO+ memory T cells of healthy and IBD controls expressed
      alpha4beta7 (72%; interquartile range, 56%-81%). In contrast, free alpha4beta7
      was detectable on only 5.6% of intestinal memory cells (interquartile range, 4.4%
      11.2%) (P < .0001) from vedolizumab-treated patients, regardless of response.
      CONCLUSIONS: In a prospective study of real-life patients with IBD, we associated
      vedolizumab drug levels with remission and inflammatory marker level. Integrin
      alpha4beta7 was blocked in almost all T cells from patients treated with
      vedolizumab, regardless of serum level of the drug or response to treatment.
      These findings indicate a need to explore alternative mechanisms that prevent
      response to vedolizumab.

PMID- 29223445
TI  - Brucella infection following total joint arthroplasty: A systematic review of the
      literature.
AB  - INTRODUCTION: The aim of this systematic review was to analyze the results of
      published treatment options in Brucella infection following total joint
      arthroplasty (TJA). METHODS: We performed a systematic review of the literature
      regarding outcomes of Brucella infection after TJA (hip and knee). We searched
      multiple databases for articles in the area published from 1950 to 2016. RESULTS:
      A total of 18 patients (12 male and 6 female; mean age 59 years) from 14
      published studies were identified. The minimum follow-up time was 6 months
      (range, 6-120 months). Seven patients were treated with debridement or
      antibrucella treatment only. Eleven patients (61%) underwent removal of the
      prosthesis and were treated with one or two-stage exchange arthroplasty. The mean
      duration of antibiotic therapy was 5.8 months. There was no relapse of infection.
      CONCLUSIONS: In the absence of loosening of the components of the prosthesis, an
      attempt to treat Brucella infection medically might be a reasonable choice. One
      or two-stage exchange arthroplasty could provide successful results without
      relapse of infection when combined with appropriate antibiotherapy. LEVEL OF
      EVIDENCE: Level III, therapeutic study.

PMID- 29223446
TI  - Structural and functional conservation of cis-acting RNA elements in coronavirus
      5'-terminal genome regions.
AB  - Structure predictions suggest a partial conservation of RNA structure elements in
      coronavirus terminal genome regions. Here, we determined the structures of stem
      loops (SL) 1 and 2 of two alphacoronaviruses, human coronavirus (HCoV) 229E and
      NL63, by RNA structure probing and studied the functional relevance of these
      putative cis-acting elements. HCoV-229E SL1 and SL2 mutants generated by reverse
      genetics were used to study the effects on viral replication of single-nucleotide
      substitutions predicted to destabilize the SL1 and SL2 structures. The data
      provide conclusive evidence for the critical role of SL1 and SL2 in HCoV-229E
      replication and, in some cases, revealed parallels with previously characterized
      betacoronavirus SL1 and SL2 elements. Also, we were able to rescue viable HCoV
      229E mutants carrying replacements of SL2 with equivalent betacoronavirus
      structural elements. The data obtained in this study reveal a remarkable degree
      of structural and functional conservation of 5'-terminal RNA structural elements
      across coronavirus genus boundaries.

PMID- 29223447
TI  - Clinical, laboratory and imaging findings in Castleman's disease - The subtype
      decides.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder with its distinct
      unicentric (uCD) and multicentric (mCD) entities. The present work aimed at
      characterizing CD in more detail. From the 775 articles found by a PubMed search,
      1133 cases were extracted. Two own cases were included. UCD was identified in 719
      (42% males) and mCD in 416 (63% males) cases. Age in uCD was 34+/-17 and in mCD
      48+/-18years. The hyaline-vascular type predominated in uCD and the plasma cell
      type in mCD. Clinical symptoms were more common in mCD. The head and neck region
      was most frequently affected in uCD and the axillary region in mCD. Prevalence of
      human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8) positivity was
      higher in mCD. In CT scans, high contrast enhancement and calcifications were
      more frequent in uCD (all p<0.0001). The two forms of CD not only differ markedly
      in their clinical, laboratory and imaging findings, but also in treatment
      response and prognosis.

PMID- 29223448
TI  - Understanding the reality of parental alienation.

PMID- 29223449
TI  - Anti HSV-2 activity of Peganum harmala (L.) and isolation of the active compound.
AB  - Genital herpes is a sexually transmitted disease caused by herpes simplex virus
      type 2 (HSV-2). Nucleoside analogues such as acyclovir (ACV) are the usual
      therapy for treating HSV infection. However, the overuse of this drug has led to
      the emergence of resistant strains. Therefore, the search for new alternative or
      complementary molecules to overcome this obstacle is needed. In this objective,
      Peganum harmala was investigated for its HSV-2 activity. The organic extracts of
      the different plant organs were evaluated for their cytotoxicity on Vero cells by
      the MTT test and anti HSV-2 activity by plaque reduction assay. Only the methanol
      seeds extract was active with a 50% inhibitory concentration (IC50) and a
      selectivity index (SI) of 161 and 13.2 MUg/mL, respectively. In addition, the
      study of the antiviral mode of action revealed that this extract exerts a
      virucidal action both during the entry of viruses and the release of the newly
      formed virions, whereas no cell protection effect was observed. The active
      compound was isolated by bio-guided purification using thin layer chromatography
      (TLC) and identified by GC-MS and HPLC-DAD-ESI-MSn as harmine. The combination of
      harmine standard compound with ACV showed a combination index (CI) of 0.5
      indicating that these two compounds have a synergic effect. This data suggests
      that harmine could be associated to ACV to improve the treatment of genital
      herpes essentially for the immunocompromised patients.

PMID- 29223450
TI  - Pesticide degrading natural multidrug resistance bacterial flora.
AB  - Multidrug-resistant (MDR) bacteria are a growing threat to humans across the
      world. Antibiotic resistance is a global problem that has developed through
      continuous antibiotic use, combinatorial antibiotic use, pesticide-antibiotic
      cross-resistance, and horizontal gene transfer, as well as various other modes.
      Pesticide-antibiotic cross-resistance and the subsequent expansion of drug
      resistant bacteria are critically documented in this review, the primary focus of
      which is to assess the impact of indiscriminate pesticide use on the development
      of microbial communities with parallel pesticide and multidrug resistance. The
      consumption of pesticide-contaminated food products and the use of broad-spectrum
      antibiotics by humans and in livestock animals have favored the development of
      both antibiotic and pesticide-resistant bacterial flora via natural selection.
      Pesticide resistance mainly develops through defensive bacterial adaptations such
      as biofilm formation, induced mutations, and horizontal/vertical gene transfer
      through plasmids or transposons, as well as through the increased expression of
      certain hydrolytic enzymes. Pesticide resistance genes are always transferred as
      gene clusters, and they may also carry genes essential for antibiotic resistance.
      Moreover, for some induced mutations, the mutated active site of the affected
      enzyme may allow degradation of both pesticides and antibiotics, resulting in
      cross-resistance. A few studies have shown that the sub-lethal exposure of wild
      type strains to herbicides induces antibiotic resistance. This review concludes
      that xenobiotic exposure leads to cross-resistance in wild microbial flora, which
      requires further study to develop therapeutic approaches to overcome the threats
      of MDR bacteria and superbugs.

PMID- 29223451
TI  - Mineralization in newborn calves contributes to health, improve the antioxidant
      system and reduces bacterial infections.
AB  - The first phase of life of dairy calves has elevated mortality indices linked
      with low immunity and sanitary challenges, mainly bacterial infections are
      involved in the pathogenesis of diarrhea, the leading cause of death. Also, other
      important problem is the nutritional deficiencies, such as the mineral
      deficiency. Thus, the aim of this study was to evaluate whether an intramuscular
      mineral supplementation based on selenium, copper, potassium, magnesium and
      phosphorus possess beneficial effects on health of dairy calves. For this, ten
      calves were divided in two groups: the group A was supplemented with injectable
      mineral, while the group B was used as control group (without mineral
      supplementation). The mineral complex was administrated via intramuscularly at
      dose of 3 mL/animal on days 2 and 14 post-birth. The total blood was collected on
      days 2, 10, 20 and 30 of life of animals in order to analyze the antioxidant
      enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase
      (GPx)), blood count and seric biochemistry linked with proteic, lipid and
      carbohydrate metabolism. Feces samples were also collected on days 10, 20 and 30
      of life of animals to perform the total bacterial count, parasitological exam and
      fecal consistency score. Moreover, the weight and corporal temperature were also
      evaluated. The mineral supplementation presented beneficial properties to calves
      from birth to the 30th of life through the increase on activity of antioxidant
      enzymes, improvement of immunity, and avoiding problems linked with diarrhea and
      anemia, can be considered an interesting approach to prevent these alterations
      linked with high mortality in the period of life.

PMID- 29223452
TI  - Antimicrobial activity of Bulbothrix setschwanensis (Zahlbr.) Hale lichen by cell
      wall disruption of Staphylococcus aureus and Cryptococcus neoformans.
AB  - In the present study, antimicrobial activity of a common Himalayan lichen viz.
      Bulbothrix setschwanensis (Zahlbr.) Hale extract in three common solvents
      (acetone, chloroform and methanol) was evaluated against six bacterial and seven
      fungal clinical strains. The acetone extract showed promising antimicrobial
      activity against S. aureus (1.56 mg/mL) and C. neoformans (6.25 mg/mL). Further,
      GC-MS analysis revealed 2,3-bis(2-methylpentanoyloxy)propyl 2-methylpentanoate
      and Ethyl 2-[(2R,3R,4aR,8aS)-3-hydroxy-2,3,4,4a,6,7,8,8a-octahydropyrano [3,2
      b]pyran-2-yl]acetate as the predominant compounds. The combination of acetone
      extract with antibacterial drugs [kanamycin (KAN), rifampicin (RIF)] and
      antifungal drugs [amphotericin B (Amp B) and fluconazole (FLC)] showed lysis of
      S. aureus and C. neoformans at non-inhibitory concentration (FICI values were
      0.31 for KAN, 0.18 for RIF, 0.37 for Amp B and 0.30 for FLC, respectively).
      Notably, the acetone extract confirmed cell wall damage of both S. aureus and C.
      neoformans cells and was clearly visualized under scanning electron microscopy
      (SEM), flow cytometry and confocal microscopy. Besides this, the three extracts
      also have less significant cytotoxic activity at MIC concentrations against
      mammalian cells (HEK-293 and HeLa). This study for the first time suggests that
      the chemical compounds present in the acetone extract of B. setschwanensis could
      be used against S. aureus and C. neoformans infections.

PMID- 29223453
TI  - HBV reactivation in rheumatic diseases patients under therapy: A meta-analysis.
AB  - BACKGROUND: Hepatitis B is one of the most common infectious diseases worldwide.
      In patients undergoing immunosuppressive therapy such as rheumatic diseases,
      reactivation of hepatitis B virus (HBV) is considered clinically important. This
      systematic review and meta-analysis were performed to determine the prevalence
      rate of HBV reactivation in rheumatic patients from different parts of the world.
      METHODS: The authors performed a systematic literature review from several
      reliable databases including Scopus, ISI Web of Science and PubMed. Furthermore,
      the keywords of this research were "Hepatitis B virus", "Rheumatic diseases",
      "HBV reactivation", "Anti-TNF", "DMARDs" and "Biologic agents". RESULTS: The
      authors selected 30 studies out of 983 for the present review. The overall
      estimation of the prevalence of HBV reactivation was 1.4 (95% confidence interval
      (CI): 1.3-1.6). Also, the heterogeneity in estimating the pooled prevalence among
      the studies was shown; Cochran Q test, P < 0.001, I2 = 99.9%. It should be noted
      that max and min reactivation rate of HBV were in Italy and France respectively.
      CONCLUSIONS: Rheumatic disease patients with resolved hepatitis B should be
      tightly monitored for possible HBV reactivation by elevation of liver enzymes and
      HBV DNA levels.

PMID- 29223454
TI  - Preparation, characterization and immunological evaluation of alginate
      nanoparticles loaded with whole inactivated influenza virus: Dry powder
      formulation for nasal immunization in rabbits.
AB  - It has become important to explore more efficient and feasible influenza
      vaccines, since epidemics of influenza virus cause hundreds of thousands of
      deaths all around the world. Improving immunogenicity of parentral influenza
      vaccines has given rise to mucosal delivery routes. In this study, alginate
      nanoparticles (NPs) were efficiently synthetized by ionic gelation method and
      influenza virus and CpG ODN or Quillaja Saponin (QS) adjuvants were actively
      incorporated into alginate NPs. The prepared particles were evaluated for both
      humoral and cellular immune responses in rabbits' nostrils. The vaccination
      started with a prime dose and followed by three boosters (two intranasal (IN) on
      days 45 and 60 and the last dose, intramuscular (IM) on day 75). HAI titer had
      increased in all the samples; although, only in the group received WV + CPG
      suspension reached to the protective HAI titer. All the immunized rabbits
      elicited significantly high sIgA levels on day 75, compared to the negative and
      the IM groups. At the end of the study, IN administration of CpG ODN adjuvant
      with virus antigen induced higher IgG level than the groups vaccinated with
      alginate NPs with or without CpG ODN (P < 0.001). As for the cellular immunity,
      CpG ODN was capable of inducing significant levels of IL-4 and TNF-alpha, either
      through inoculation along with the virus suspension or as incorporated in
      alginate NPs. According to the obtained data, CpG ODN adjuvant showed higher
      immunogenic potential as part of a vaccine delivery system than QS. Moreover,
      applying alginate polymer as a nasal delivery system carrier was not deemed
      immunogenic against influenza whole virus.

PMID- 29223455
TI  - Recyclable colorimetric sensor of Cr3+ and Pb2+ ions simultaneously using a
      zwitterionic amino acid modified gold nanoparticles.
AB  - In this work, a rapid, simple and sensitive colorimetric sensor for simultaneous
      (or respective) detection of Cr3+ and Pb2+ using tyrosine functionalized gold
      nanoparticles (AuNPsTyr) has been developed. Tyrosine, a natural and zwitterionic
      amino acid, could be as a reducing and capping agent to synthesise AuNPs and
      allow for the simultaneous and selective detection of Cr3+ and Pb2+. Upon the
      addition of Cr3+ or Pb2+ (a combination of them), the color of AuNPsTyr solution
      changes from red to blue grey and the characteristic surface plasmon resonance
      (SPR) band is red-shifted to 580nm due to the aggregation of AuNPs.
      Interestingly, the aggregated AuNPsTyr can be regnerated and recycled by removing
      Pb2+ and Cr3+. Even after 3 rounds, AuNPsTyr show almost the same A580nm/A520nm
      value for the assays of Pb2+ and Cr3+, indicating the good recyclability of the
      colorimetric sensor. The responding time (within 1min) and sensitivity of the
      colorimetric sensor are largely improved after the addition of 0.1M NaCl.
      Moreover, the AuNPsTyr aggregated by Cr3+ or Pb2+ (a combination of them) show
      excellent selectivity compared to other metal ions (Cr3+, Pb2+,
      Fe2+,Cu2+,Zn2+,Cr6+,Ni2+,Co2+,Hg2+,Mn2+,Mg2+,Ca2+,Cd2+). More importantly, the
      developed sensor manifests good stability at room temperature for 3months, which
      has been successfully used to determine Cr3+ and Pb2+ in the real water samples
      with a high sensitivity.

PMID- 29223456
TI  - Simplex optimization of the variables influencing the determination of pefloxacin
      by time-resolved chemiluminescence.
AB  - A new chemiluminescence (CL) detection system combined with flow injection
      analysis (FIA) for the determination of Pefloxacin is proposed. The determination
      is based on an energy transfer from Pefloxacin to terbium (III). The metal ion
      enhances the weak CL signal produced by the KMnO4/H2SO3/Pefloxacin system. A
      modified simplex method was used to optimize chemical and instrumental variables.
      The influence of the interaction of the permanganate, Tb (III), sodium sulphite
      and sulphuric acid concentrations, flow rate and injected sample volume was
      thoroughly investigated by using a modified simplex optimization procedure. The
      results revealed a strong direct relationship between flow rate and CL intensity
      throughout the studied range that was confirmed by a gamma test. The response
      factor for the CL emission intensity was used to assess performance in order to
      identify the optimum conditions for maximization of the response. Under such
      conditions, the CL response was proportional to the Pefloxacin concentration over
      a wide range. The detection limit as calculated according to Clayton's criterion
      13.7MUgL-1. The analyte was successfully determined in milk samples with an
      average recovery of 100.6+/-9.8%.

PMID- 29223457
TI  - Adsorption behavior and mechanism of acidic blue 25 dye onto cucurbit[8]uril: A
      spectral and DFT study.
AB  - The acidic blue 25 (AB25) dye was efficiently adsorbed by CB [8]; the saturated
      adsorption capacity (qexp) reached 434.8mg/g and was far higher than those of
      previous reported adsorbents. The Langmuir and Freundich isotherms were used to
      fit the equilibrium data, and the results showed that the Freundlich isotherm
      seemed to agree better with the AB25 adsorption. The adsorption kinetics followed
      the pseudo-second-order model. Calculated thermodynamic parameters showed that
      the adsorption of AB25 onto CB [8] was a spontaneous and enthalpy-driven process.
      The adsorption mechanism was explored by N2 adsorption-desorption, TG, FT-IR, UV
      vis as well as MD simulation and DFT calculations. TG analysis revealed that a
      new inclusion complex was produced, and FT-IR,UV-vis spectrum and DFT
      calculations verify its structure. In this inclusion complex, the AB25 dye
      molecule inserted into cavities of CB [8] from portal, and the sulfonate and
      phenyl groups stayed in the hydrophobic cavity. TDDFT calculations indicated that
      all excitation arisen from pi->pi* transition.

PMID- 29223458
TI  - Determination of zinc oxide content of mineral medicine calamine using near
      infrared spectroscopy based on MIV and BP-ANN algorithm.
AB  - Near-infrared (NIR) spectroscopy has been widely used in the analysis fields of
      traditional Chinese medicine. It has the advantages of fast analysis, no damage
      to samples and no pollution. In this research, a fast quantitative model for zinc
      oxide (ZnO) content in mineral medicine calamine was explored based on NIR
      spectroscopy. NIR spectra of 57 batches of calamine samples were collected and
      the first derivative (FD) method was adopted for conducting spectral
      pretreatment. The content of ZnO in calamine sample was determined using
      ethylenediaminetetraacetic acid (EDTA) titration and taken as reference value of
      NIR spectroscopy. 57 batches of calamine samples were categorized into
      calibration and prediction set using the Kennard-Stone (K-S) algorithm. Firstly,
      in the calibration set, to calculate the correlation coefficient (r) between the
      absorbance value and the ZnO content of corresponding samples at each wave
      number. Next, according to the square correlation coefficient (r2) value to
      obtain the top 50 wave numbers to compose the characteristic spectral bands
      (4081.8-4096.3, 4188.9-4274.7, 4335.4, 4763.6,4794.4-4802.1, 4809.9, 4817.6
      4875.4cm-1), which were used to establish the quantitative model of ZnO content
      using back propagation artificial neural network (BP-ANN) algorithm. Then, the 50
      wave numbers were operated by the mean impact value (MIV) algorithm to choose
      wave numbers whose absolute value of MIV greater than or equal to 25, to obtain
      the optimal characteristic spectral bands (4875.4-4836.9, 4223.6-4080.9cm-1). And
      then, both internal cross and external validation were used to screen the number
      of hidden layer nodes of BP-ANN. Finally, the number 4 of hidden layer nodes was
      chosen as the best. At last, the BP-ANN model was found to enjoy a high accuracy
      and strong forecasting capacity for analyzing ZnO content in calamine samples
      ranging within 42.05-69.98%, with relative mean square error of cross validation
      (RMSECV) of 1.66% and coefficient of determination (R2) of 95.75% in internal
      cross and relative mean square error of prediction (RMSEP) of 1.98%, R2 of 97.94%
      and ratio of performance to deviation (RPD) of 6.11 in external validation.

PMID- 29223459
TI  - Synthesis and studies of axial chiral bisbenzocoumarins: Aggregation-induced
      emission enhancement properties and aggregation-annihilation circular dichroism
      effects.
AB  - Axial chiral bisbenzocoumarins were synthesized for the first time by converting
      naphthanol units in 1,1'-binaphthol (BINOL) molecule to the benzocoumarin rings.
      The substitute groups on 3,3'-positions of bisbenzocoumarins showed significant
      influence on their aggregation-induced emission enhancement (AEE) properties. It
      was also found that BBzC1 with ester groups on 3,3'-positions exhibit an abnormal
      aggregation-annihilation circular dichroism (AACD) phenomenon, which could be
      caused by the decrease of the dihedral angle between adjacent benzocoumarin rings
      in the aggregation state. The single crystal structure of BBzC1 showed that the
      large dihedral angle in molecule prohibited the strong pi-pi stacking
      interactions, which could be main factors for its AEE properties.

PMID- 29223460
TI  - Investigation of anticancer properties of caffeinated complexes via computational
      chemistry methods.
AB  - Computational investigations were performed for 1,3,7-trimethylpurine-2,6-dione,
      3,7-dimethylpurine-2,6-dione, their Ru(II) and Os(III) complexes. B3LYP/6
      311++G(d,p)(LANL2DZ) level was used in numerical calculations. Geometric
      parameters, IR spectrum, 1H-, 13C and 15N NMR spectrum were examined in detail.
      Additionally, contour diagram of frontier molecular orbitals (FMOs), molecular
      electrostatic potential (MEP) maps, MEP contour and some quantum chemical
      descriptors were used in the determination of reactivity rankings and active
      sites. The electron density on the surface was similar to each other in studied
      complexes. Quantum chemical descriptors were investigated and the anticancer
      activity of complexes were more than cisplatin and their ligands. Additionally,
      molecular docking calculations were performed in water between related complexes
      and a protein (ID: 3WZE). The most interact complex was found as Os complex. The
      interaction energy was calculated as 342.9kJ/mol.

PMID- 29223461
TI  - Antenatal Consultations at Extreme Prematurity: A Systematic Review of Parent
      Communication Needs.
AB  - OBJECTIVE: To synthesize and describe parental expectations on how healthcare
      professionals should interact with them during a peripartum, antenatal
      consultation for extremely preterm infants. STUDY DESIGN: For this systematic
      literature review with textual narrative synthesis, we included studies that
      explored parental perspectives regarding the antenatal consultation for an
      extremely preterm infant. Electronic searches of Medline, CINAHL, PsycInfo, and
      Embase were conducted, along with a search of the grey literature. Quality
      appraisal was conducted using the guide by Walsh and Downe. Two independent
      reviewers reviewed 783 titles, of which 130 abstracts then 40 full-text articles
      were reviewed. Final data abstraction includes 19 studies. We predetermined 6
      topics of interest (setting, timing, preferred healthcare professional,
      information, resources, and parents-physician interaction) to facilitate thematic
      analysis. RESULTS: In consideration of the variability of parents' specific
      desires, six predetermined topics and additional overarching themes such as
      perception of support, degree of understanding, hope, spirituality, and decision
      making influences emerged. Studies suggest the quality of the antenatal
      consultation is not purely about information content, but also the manner in
      which it is provided. Limitations include thematic analysis that can potentially
      lead to the exclusion of important nuances. Relevant studies may have been missed
      if published outside the healthcare literature. CONCLUSIONS: The findings may
      inform clinical practice guidelines. This paper includes suggested strategies
      related to parents' perspectives that may facilitate communication during
      antenatal consultation for an extremely preterm infant. These strategies may also
      support parental engagement and satisfaction.

PMID- 29223462
TI  - Social identity and cooperation in cultural evolution.
AB  - I discuss the function of social identity signaling in facilitating cooperative
      group formation, and how the nature of that function changes with the structure
      of social organization. I propose that signals of social identity facilitate
      assortment for successful coordination in large-scale societies, and that the
      multidimensional, context-dependent nature of social identity is crucial for
      successful coordination when individuals have to cooperate in different contexts.
      Furthermore, the structure of social identity is tied to the structure of
      society, so that as societies grow larger and more interconnected, the landscape
      of social identities grows more heterogeneous. This discussion bears directly on
      the need to articulate the dynamics of emergent, ephemeral groups as a major
      factor in human cultural evolution.

PMID- 29223463
TI  - Terfenadine metabolism of human cytochrome P450 2J2 containing genetic variations
      (G312R, P351L and P115L).
AB  - The human cytochrome P450 2J2 is involved in several metabolic reactions,
      including the oxidation of important therapeutics and epoxidation of endogenous
      arachidonic acid. At least ten genetic variations of P450 2J2 have been
      identified, but their effects on enzymatic activity have not been clearly
      characterized. Here, we evaluated the functional effects of three genetic
      variations of P450 2J2 (G312R, P351L, and P115L). Recombinant enzymes of wild
      type and three variant P450 2J2 were heterologously expressed in Escherichia coli
      and purified. P450 expression levels in the wild-type and two variants (P351L and
      P115L) were 142-231 nmol per liter culture, while the G312R variant showed no
      holoenzyme peak in the CO-binding spectra. Substrate binding titrations to
      terfenadine showed that the wild-type and two variants displayed Kd values of
      0.90-2.2 MUM, indicating tight substrate binding affinities. Steady-state kinetic
      analysis for t-butyl methyl hydroxylation of terfenadine indicated that two
      variant enzymes had similar kcat and Km values to wild-type P450 2J2. The
      locations of mutations in three-dimensional structural models indicated that the
      G312R is located in the I-helix region near the formal active site in P450 2J2
      and its amino acid change affected the structural stability of the P450 heme
      environment.

PMID- 29223464
TI  - Data journeys: Identifying social and technical barriers to data movement in
      large, complex organisations.
AB  - Managers in complex organisations often have to make decisions on whether new
      software developments are worth undertaking or not. Such decisions are hard to
      make, especially at an enterprise level. Both costs and risks are regularly
      underestimated, despite the existence of a plethora of software and systems
      engineering methodologies aimed at predicting and controlling them. Our objective
      is to help managers and stakeholders of large, complex organisations (like the
      National Health Service in the UK) make better informed decisions on the costs
      and risks of planned new software systems that will reuse or extend their
      existing information infrastructure. We analysed case studies describing new
      software developments undertaken by providers of health care services in the UK,
      looking for common points of risk and high cost. The results highlighted the
      movement of data within and between organisations as a key factor. Data movement
      can be hindered by numerous technical barriers, but also by other challenges
      arising from social aspects of the organisation. These latter aspects are often
      harder to predict, and are ignored by many of the more common software
      engineering methodologies. In this paper, we propose data journey modelling, a
      new method aiming to predict places of high cost and risk when existing data
      needs to move to a new development. The method is lightweight and combines
      technical and social aspects, but relies only on information that is likely to be
      already known to key stakeholders, or will be cheap to acquire. To assess the
      effectiveness of our method, we conducted a retrospective evaluation in an NHS
      Foundation Trust hospital. Using the method, we were able to predict most of the
      points of high cost/risk that the hospital staff had identified, along with
      several other possible directions that the staff did not identify for themselves,
      but agreed could be promising.

PMID- 29223465
TI  - Biomedical applications of genome-scale metabolic network reconstructions of
      human pathogens.
AB  - The growing global threat of antibiotic resistant human pathogens has coincided
      with improved methods for developing and using genome-scale metabolic network
      reconstructions. Consequently, there has been an increase in the number of high
      quality reconstructions of relevant human and zoonotic pathogens. Novel
      biomedical applications of pathogen reconstructions focus on three key aspects of
      pathogen behavior: the evolution of antibiotic resistance, virulence factor
      production, and host-pathogen interactions. New methods using these
      reconstructions aim to improve understanding of microbe pathogenicity and guide
      the development of new therapeutic strategies. This review summarizes the latest
      ways that genome-scale metabolic network reconstructions have been used to study
      human pathogens and suggests future applications with the potential to mitigate
      infectious disease.

PMID- 29223467
TI  - Does insulin therapy matter? Determinants of diabetes care outcomes.
AB  - OBJECTIVE: To evaluate adherence to care standards for people with diabetes
      (PWDs) on insulin therapy versus PWDs who are not on insulin therapy, controlling
      for social determinants. RESEARCH DESIGN AND METHODS: Utilizing the United States
      2015 Behavioral Risk Factor Surveillance System Survey, this study used logistic
      regression analyses to estimate differences in self-care behaviors, healthcare
      provider quality of care, and diabetic complications for individuals on insulin
      therapy and individuals not on insulin therapy. RESULTS: PWDs on insulin therapy
      are more likely to adhere to self-care measures (self-glucose checks [OR: 7.57],
      self-foot checks [OR: 1.27], diabetes class participation [OR: 1.96]), adherence
      to provider care standards (diabetes-related doctor visits [OR: 1.24],
      comprehensive foot exam [OR: 1.80], dilated eye exam [OR: 1.34]), and to self
      report diabetic complications (retinopathy [OR: 2.77], kidney disease [OR:2.14]),
      controlling for sociodemographic variables. CONCLUSION: PWDs on insulin and their
      healthcare providers are more likely to meet the treatment goals set by the
      American Diabetes Association. PWDs on insulin therapy may have better overall
      relationships with providers due to a reduction in stigmatization based on the
      social construction of diabetes.

PMID- 29223466
TI  - Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure
      in mice.
AB  - Pulmonary hypertension (PH) frequently occurs in infants with bronchopulmonary
      dysplasia (BPD), causing increased mortality and right ventricular (RV)
      dysfunction that persists into adulthood. A first step in developing better
      therapeutic options is identifying and characterizing an appropriate animal
      model. Previously, we characterized the short-term morbidities of a model in
      which C57BL/6J wild-type (WT) mice were exposed to 70% O2 (hyperoxia) during the
      neonatal period. Here, we aimed to determine the long-term morbidities using lung
      morphometry, echocardiography (Echo), and cardiac magnetic resonance imaging
      (cMRI). The major highlight of this study is the use of the state-of-the art
      imaging technique, cMRI, in mice to characterize the long-term cardiac effects of
      neonatal hyperoxia exposure. To this end, WT mice were exposed to 21% O2
      (normoxia) or hyperoxia for two weeks of life, followed by recovery in normoxia
      for six weeks. Alveolarization, pulmonary vascularization, pulmonary
      hypertension, and RV function were quantified at eight weeks. We found that
      hyperoxia exposure resulted in persistent alveolar and pulmonary vascular
      simplification. Furthermore, the Echo and cMRI studies demonstrated that
      hyperoxia-exposed mice had signs of PH and RV dysfunction as indicated by
      increased RV pressure, mass, and end-systolic and -diastolic volumes, and
      decreased RV stroke volume and ejection fractions. Taken together, our results
      demonstrate that neonatal hyperoxia exposure in mice cause cardiopulmonary
      morbidities that persists into adulthood and provides evidence for the use of
      this model to develop novel therapies for BPD infants with PH.

PMID- 29223468
TI  - Postmastectomy radiation therapy: What factors are important in recommending
      treatment to patients undergoing "Sparing" mastectomies.

PMID- 29223469
TI  - Oncological and functional outcomes of elderly men treated with HIFU vs.
      minimally invasive radical prostatectomy: A propensity score analysis.
AB  - AIM: To assess outcomes of whole gland high-intensity focused ultrasound (HIFU)
      as compared with minimally-invasive radical prostatectomy (MIRP) in elderly
      patients. MATERIALS & METHODS: Patients aged >=70 years with, cT1-cT2 disease,
      biopsy Gleason score (GS) 3 + 3 or 3 + 4 and preoperative PSA <=10 ng/mL were
      submitted to either whole-gland HIFU or MIRP. Propensity-score matching analysis
      was performed to ensure the baseline equivalence of groups. Follow-up visits were
      routinely performed assessing PSA and urinary function according to the
      International Continence Score (ICS) and the International Prostatic Symptoms
      Score (IPSS) questionnaires. Estimated rates of salvage-treatment free survival
      (SFS) overall-survival (OS), cancer-specific survival (CSS) and metastasis-free
      survival (MTS) were assessed and compared. RESULTS: Overall, 84 (33.3%) and 168
      (66.7%) patients were treated with HIFU and MIRP, respectively. MIRP was
      associated with a 5-yrs SFS of 93.4% compared to 74.8% for HIFU (p < 0.01). The
      two groups did not differ in terms of OS and MTS. No cancer-related deaths were
      registered. Patients treated with HIFU showed better short-term (6-mos)
      continence outcomes [mean-ICS: 1.7 vs. 4.8; p = 0.005] but higher IPSS mean
      scores at 12-mos assessment. A comparable rate of patients experiencing post
      treatment Clavien-Dindo grade >=III complications was observed within the two
      groups. CONCLUSIONS: Whole-gland HIFU is a feasible treatment in elderly men with
      low-to intermediate-risk PCa and could be considered for patients either unfit
      for surgery, or willing a non-invasive treatment with a low morbidity burden,
      although a non-negligible risk of requiring subsequent treatment for recurrence
      should be expected.

PMID- 29223470
TI  - REVEAL risk scores applied to riociguat-treated patients in PATENT-2: Impact of
      changes in risk score on survival.
AB  - BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management
      (REVEAL) risk score (RRS) calculator was developed using data derived from the
      REVEAL registry, and predicts survival in patients with pulmonary arterial
      hypertension (PAH) based on multiple patient characteristics. Herein we applied
      the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label
      PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs
      placebo on RRS in PATENT-1, and investigated the prognostic implications of
      change in RRS during PATENT-1 on long-term outcomes in PATENT-2. METHODS: RRS was
      calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT
      2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were
      made for survival and clinical worsening-free survival in PATENT-2 to evaluate
      the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2.
      RESULTS: A total of 396 patients completed PATENT-1 and participated in PATENT-2.
      In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p
      = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and
      at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly
      associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675,
      0.705 and 0.804, respectively) and clinical worsening-free survival (hazard
      ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2.
      CONCLUSIONS: RRS at baseline and Week 12, and change in RRS, were significant
      predictors of both survival and clinical worsening-free survival. These data
      support the long-term predictive value of the RRS in a controlled study
      population.

PMID- 29223471
TI  - [Clinical-epidemiological study of Bordetella pertussis infection in the Gran
      Canaria island in the period, 2008-2016].
AB  - OBJECTIVE: Describe the epidemiological and clinical pattern of Bordetella
      pertussis infection (whooping cough) among hospitalised infants less than one
      year-old in a paediatric hospital in Gran Canaria. PATIENTS AND METHODS: A
      retrospective review of the patient hospital records was performed, and recording
      only those with a microbiological diagnosis of pertussis infection detected using
      polymerase chain reaction, from January 2008 to December 2016. RESULTS: A total
      of 110 patients were identified, of which 105 (95.4%) were less than 6 months
      old, and 59.1% were males. The annual incidence of hospital admissions was
      estimated between 13.7 to 425.0 cases per 100,000 infants <12 months old, with
      2peaks in 2011 and 2015. Household members were the main potential sources of
      infection. Main clinical features were pertussis cough associated with signs of
      catarrh, cyanosis, and lymphocytosis. Complications occurred in 15.4% of the
      patients (mainly pneumonia), but the outcome was favourable in all the cases. A
      lower age and non-vaccination were associated with an increased risk of
      developing complications (P<.05). Viral co-infection occurred in 31.6% of infants
      diagnosed with pertussis. CONCLUSIONS: The incidence of pertussis has increased
      in the last years in Gran Canaria, with a lower development of complications and
      mortality rates compared with the previous period. Lower age and non-vaccination
      status are considered risk factors for developing complications. Vaccination in
      pregnant women will probably lead to a decline in the incidence in the future,
      especially in infants younger than 6 months.

PMID- 29223472
TI  - [Excess weight and abdominal obesity in Galician children and adolescents].
AB  - INTRODUCTION AND OBJECTIVES: The excess of weight, mainly obesity, during
      childhood and adolescence increases morbimortality risk in adulthood. The aim of
      this article is to estimate both the overall prevalence, as well as according to
      age and gender, of underweight, overweight, obesity and abdominal obesity among
      schoolchildren aged between 6-15-years-old in the school year 2013-2014. MATERIAL
      AND METHODS: Data were taken from a cross-sectional community-based study carried
      out on a representative sample, by gender and age, of the Galician population
      aged between 6 and 15 years-old. The prevalence of underweight, overweight, and
      obese children (Cole's cut-off criteria) and abdominal obesity (Taylor's cut-off
      criteria) were estimated after performing objective measurements of height,
      weight and waist circumference at school. RESULTS: A total of 7,438 students were
      weighed and measured in 137 schools. The prevalence of overweight and obese
      individuals was 24.9% and 8.2%, respectively. The prevalence of abdominal obesity
      was 25.8%, with 4% of children with normal weight having abdominal obesity.
      CONCLUSIONS: These data highlight the need to promote primary prevention measures
      at early ages in order to decrease the occurrence of the premature onset of
      disease in the future. The prevalence of excess weight is underestimated if
      abdominal obesity is not taken into consideration.

PMID- 29223473
TI  - [Cryptogenic West syndrome: Clinical profile, response to treatment and
      prognostic factors].
AB  - INTRODUCTION: West syndrome (WS) is an age-dependent epileptic encephalopathy in
      which the prognosis varies according to the, not always identified, underlying
      origin. OBJECTIVES: To define the profile of cryptogenic (a least studied
      isolated sub-group) WS, in Spain. To study its outcome, response to different
      treatments, and to establish prognostic factors. PATIENTS AND METHODS: The study
      included a review of the medical records of 16 patients diagnosed with
      cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6
      years, with a minimum of 2 years. RESULTS: The large majority (11/16) were male.
      The mean age at onset was 6 months, and 6/16 had a family history of idiopathic
      epilepsy. The first line treatment with vigabatrin had an electrical-clinical
      response in 5/16 patients, with the remaining cases responding to
      adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed
      to other types of epilepsy, with no difference between those treated with
      vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH,
      with no retinal involvement being observed with vigabatrin. The aetiological
      cause was found in 2/16. Being female, late onset, and early control of the
      hypsarrhythmia, were factors of a good prognosis. CONCLUSIONS: The overall
      prognosis of cryptogenic WS was more serious than expected. Although the
      incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy
      was the most common, with it appearing within the first 2 years of the diagnosis.
      The initial response to vigabatrin was lower than expected, but the long-term
      result was comparable to ACTH.

PMID- 29223475
TI  - Insights from clinical experience in treating IVF poor responders.
AB  - 'Poor responders' is a term used to describe a subpopulation of IVF patients who
      do not respond well to ovarian stimulation with gonadotrophins. While there is no
      standard definition of a poor responder, these patients tend to be of advanced
      maternal age (>=40 years), have a history of poor ovarian response with
      conventional stimulation protocols, and/or have low ovarian reserve. Despite the
      heterogeneity of this patient group, there are characteristics and needs common
      to many poor responders that can be addressed through a holistic approach.
      Stimulation during the earlier stages of follicle maturation may help synchronize
      follicle development for improved response to later gonadotrophin stimulation,
      and supplementation with dehydroepiandrosterone or human growth hormone may
      promote early follicle development in poor responders. IVF protocols should be
      specifically tailored to poor responders to complement the patient's natural
      cycle. Because poor responders tend to have high levels of stress and anxiety,
      patients should receive psychological counselling and support, both prior to and
      during IVF cycles, to ensure optimal outcomes and improve patients' experience.
      It is important to set realistic expectations with poor responders and their
      partners to help patients make informed decisions and better manage their
      distress and anxiety.

PMID- 29223474
TI  - Fine-tuning of store-operated calcium entry by fast and slow Ca2+-dependent
      inactivation: Involvement of SARAF.
AB  - Store-operated Ca2+ entry (SOCE) is a functionally relevant mechanism for Ca2+
      influx present in electrically excitable and non-excitable cells. Regulation of
      Ca2+ entry through store-operated channels is essential to maintain an
      appropriate intracellular Ca2+ homeostasis and prevent cell damage. Calcium
      release activated channels exhibit Ca2+-dependent inactivation mediated by two
      temporally separated mechanisms: fast Ca2+-dependent inactivation takes effect in
      the order of milliseconds and involves the interaction of Ca2+ with residues in
      the channel pore while slow Ca2+-dependent inactivation (SCDI) develops over tens
      of seconds, requires a global rise in [Ca2+]cyt and is a mechanism regulated by
      mitochondria. Recent studies have provided evidence that the protein SARAF (SOCE
      associated regulatory factor) is involved in the mechanism underlying SCDI of
      Orai1. SARAF is an endoplasmic reticulum (ER) membrane protein that associates
      with STIM1 and translocate to plasma membrane-ER junctions in a STIM1-dependent
      manner upon store depletion to modulate SOCE. SCDI mediated by SARAF depends on
      the location of the STIM1-Orai1 complex within a PI(4,5)P2-rich microdomain.
      SARAF also interacts with Orai1 and TRPC1 in cells endogenously expressing STIM1
      and cells with a low STIM1 expression and modulates channel function. This review
      focuses on the modulation by SARAF of SOCE and other forms of Ca2+ influx
      mediated by Orai1 and TRPC1 in order to provide spatio-temporally regulated Ca2+
      signals.

PMID- 29223476
TI  - Fecundity in an infertile man with r(15) - a challenge to the current paradigm.
AB  - Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth
      failure, mental disabilities, cafe-au-lait spots, specific facial features,
      fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected
      individuals reported in the literature, none were assessed for the precise
      breakpoint positioning, which creates uncertainty in defining a specific
      phenotype for the deleted segment. This study reports for the first time the
      vertical transmission of r(15) in three consecutive generations of a family,
      including a subfertile man, his mother and his newborn infant. Array comparative
      genomic hybridization results revealed a 563 kb deletion of 15q26.3, overlapping
      the OMIM genes SNRP1, PCSK6 and TM2D3. The hemizygosity was confirmed with real
      time quantitative PCR. Regarding haploinsufficiency in 15q26.3, based on
      phenotypic characteristics of the carriers, the only rational conclusion is that
      SNRPA1, PCSK6 and TM2D3 are not gene-dosage sensitive and are probably inherited
      in an autosomal-recessive manner. Given growth deficiency in r(15) carriers, this
      shows that the growth retardation cannot be attributed entirely to IGF1R. The
      predominance of female patients with r(15) is the next as yet unanswered
      question; incomplete penetrance and/or variable expression of gene(s) in
      different genders may be involved, but further evidence is needed to support this
      idea.

PMID- 29223477
TI  - Immuno-oncology from the perspective of somatic evolution.
AB  - The past years have witnessed significant success for cancer immunotherapies that
      activate a patient's immune system against their cancer cells. At the same time
      our understanding of the genetic changes driving tumor evolution have progressed
      dramatically. The study of cancer genomes has shown that tumors are best
      understood as cell populations governed by the rules of evolution, leading to the
      emergence and spread of cell lineages with pathogenic mutations. Moreover,
      somatic evolution can explain the acquisition of mutations conferring drug
      resistance in the ever-lasting battle for reaching even fitter cell states. Here,
      we review the current state of the art of somatic cancer evolution and mechanisms
      of immune control and escape. We also revisit the principles of immunotherapy
      from the perspective of somatic evolution and discuss the basic rules of
      resistance to immunotherapies as dictated by evolution.

PMID- 29223478
TI  - Phase II trial of veliparib in patients with previously treated BRCA-mutated
      pancreas ductal adenocarcinoma.
AB  - PURPOSE: BRCA-associated cancers have increased sensitivity to poly(ADP-ribose)
      polymerase inhibitors (PARPis). This single arm, non-randomised, multicentre
      phase II trial evaluated the response rate of veliparib in patients with
      previously treated BRCA1/2- or PALB2-mutant pancreatic adenocarcinoma (PDAC).
      METHODS: Patients with stage III/IV PDAC and known germline BRCA1/2 or PALB2
      mutation, 1-2 lines of treatment, Eastern Cooperative Oncology Group 0-2, were
      enrolled. Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400
      mg twice-daily (N = 15) days 1-28. The primary end-point was to determine the
      response rate of veliparib; secondary end-points included progression-free
      survival (PFS), duration of response, overall survival (OS) and safety. RESULTS:
      Sixteen patients were enrolled; male N = 8 (50%). Median age was 52 years (range
      43-77). Five (31%) had a BRCA1 and 11 (69%) had a BRCA2 mutation. Fourteen (88%)
      patients had received prior platinum-based therapy. No confirmed partial
      responses (PRs) were seen: one (6%) unconfirmed PR was observed at 4 months with
      disease progression (PD) at 6 months; four (25%) had stable disease (SD), whereas
      11 (69%) had PD as best response including one with clinical PD. Median PFS was
      1.7 months (95% confidence interval [CI] 1.57-1.83) and median OS was 3.1 months
      (95% CI 1.9-4.1). Six (38%) patients had grade III toxicity, including fatigue (N
      = 3), haematology (N = 2) and nausea (N = 1). CONCLUSIONS: Veliparib was well
      tolerated, but no confirmed response was observed although four (25%) patients
      remained on study with SD for >= 4 months. Additional strategies in this
      population are needed, and ongoing trials are evaluating PARPis combined with
      chemotherapy (NCT01585805) and as a maintenance strategy (NCT02184195).

PMID- 29223479
TI  - Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety
      study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant
      anthracycline-containing and anthracycline-free chemotherapy regimens in patients
      with HER2-positive early breast cancer.
AB  - BACKGROUND: We report long-term efficacy and cardiac safety outcomes in patients
      with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus
      trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.
      METHODS: Descriptive efficacy analyses were conducted in patients randomised to
      group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance]
      plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5
      fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m2 5
      fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel
      [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 if well tolerated]), B (cycles 1-3:
      FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned
      previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75
      mg/m2, without dose escalation], and carboplatin [AUC 6]), five years after
      randomisation of the last patient. This study is registered with
      ClinicalTrials.gov, number NCT00976989. RESULTS: Three-year Kaplan-Meier survival
      estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79
      95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free
      survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard
      ratio for total pathological complete response (tpCR) versus no tpCR was 0.27
      (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76
      (5.4%) patients in groups A-C had any-grade left ventricular systolic
      dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left
      ventricular ejection fraction declines >=10% from baseline to <50%. CONCLUSIONS:
      Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had
      improved DFS. No new safety signals were identified.

PMID- 29223480
TI  - Enlisting the willing: A study of healthcare professional-initiated and opt-in
      biobanking consent reveals improvement opportunities throughout the registration
      process.
AB  - Biobanking consent processes should accord with patients' preferences and be
      offered in a consistent and systematic manner. However, these aims can be
      difficult to achieve under healthcare professionals' (HCPs) time-constrained
      workflows, resulting in low participation rates. This current perspective
      provides a brief overview of HCP involvement in consent and reports new data on
      participant attrition at each step of the biobanking consent process as
      experienced by 113 patients at an Australian tertiary cancer centre. To determine
      attrition in this HCP-driven consent process, we reviewed medical records for the
      following events: inclusion of biobanking consent forms; visible patient and HCP
      signatures; consent status selected (decline or accept) and specimen registration
      with local biobank. Accessible medical records revealed the following data: 75 of
      85 records included viewable forms; 22 of 85 records included patient and 19 of
      85 included HCP signatures; 15 of 85 records included signed and completed forms
      and 3 of 85 had samples banked with annotated clinical data. We compared these
      data with self-reported experiences of being approached to participate by HCPs.
      Of the 15 participants (17.6%) who successfully completed consent, only five
      could recall being asked and providing consent. The low enrolment rate is a
      considerable lost opportunity because most patients (59%) who were not asked to
      participate indicated they would have consented if asked. Furthermore, in
      comparing self-reported experiences with medical records, we believe cancer
      patients' preferences for participation are mismatched with actual biobanking
      enrolment, which has considerable attrition at each step in the consent process.

PMID- 29223481
TI  - Can breast cancer patients with HER2 dual-equivocal tumours be managed as HER2
      negative disease?
AB  - BACKGROUND: Increasing human epidermal growth factor receptor 2 (HER2)
      immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual
      equivocal breast tumours are reported after the 2013 American Society of Clinical
      Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of
      this study is to investigate the clinico-pathologic characteristics, treatment
      patterns and disease outcome of these patients with HER2 dual-equivocal tumours.
      PATIENTS AND METHODS: Patients with HER2 IHC 2+ and available FISH results were
      retrospectively analysed from the Comprehensive Breast Health Center, Shanghai
      Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive,
      dual-equivocal and -negative groups. Patient characteristics, systemic treatment
      patterns and survival were compared among these groups. Reverse transcriptase
      polymerase chain reaction-based assays were applied to test HER2 mRNA expression
      level. RESULTS: Among 691 patients included, 133 (19.25%) were HER2 positive, 25
      (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate
      and multivariate analyses stated that HER2 dual-equivocal tumours shared more
      similarity with HER2-negative tumours, whereas HER2-positive tumours had rather
      different clinico-pathologic features. HER2 dual-equivocal tumours had similar
      HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much
      less compared with HER2-positive breast cancer. Besides, adjuvant systemic
      treatment patterns were comparable between HER2-negative and dual-equivocal
      tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment.
      There was no survival difference among these three groups (P = 0.43). CONCLUSION:
      HER2 dual-equivocal tumours share more similarity with HER2-negative disease in
      terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic
      treatment patterns and disease outcome, which deserves further clinical
      evaluation.

PMID- 29223482
TI  - Reactor performance and energy analysis of solid state anaerobic co-digestion of
      dairy manure with corn stover and tomato residues.
AB  - Anaerobic co-digestion is commonly believed to be benefical for biogas
      production. However, additional of co-substrates may require additional energy
      inputs and thus affect the overall energy efficiency of the system. In this
      study, reactor performance and energy analysis of solid state anaerobic digestion
      (SS-AD) of tomato residues with dairy manure and corn stover were investigated.
      Different fractions of tomato residues (0, 20, 40, 60, 80 and 100%, based on
      volatile solid weight (VS)) were co-digested with dairy manure and corn stover at
      15% total solids. Energy analysis based on experimental data was conducted for
      three scenarios: SS-AD of 100% dairy manure, SS-AD of binary mixture (60% dairy
      manure and 40% corn stover, VS based), and SS-AD of ternary mixture (36% dairy
      manure, 24% corn stover, and 40% tomato residues, VS based). For each scenario,
      the energy requirements for individual process components, including feedstock
      collection and transportation, feedstock pretreatment, biogas plant operation,
      digestate processing and handling, and the energy production were examined.
      Results showed that the addition of 20 and 40% tomato residues increased methane
      yield compared to that of the dairy manure and corn stover mixture, indicating
      that the co-digestion could balance nutrients and improve the performance of
      solid-state anaerobic digestion. The energy required for heating substrates had
      the dominant effect on the total energy consumption. The highest volatile solids
      (VS) reduction (57.0%), methane yield (379.1 L/kg VSfeed), and net energy
      production were achieved with the mixture of 24% corn stover, 36% dairy manure,
      and 40% tomato residues. Thus, the extra energy input for adding tomato residues
      for co-digestion could be compensated by the increase of methane yield.

PMID- 29223484
TI  - A third dose of measles vaccine is needed in young Korean health care workers.

PMID- 29223483
TI  - Differences by sex in IgG levels following infant and childhood vaccinations: An
      individual participant data meta-analysis of vaccination studies.
AB  - BACKGROUND: If immune responses to vaccination differ between males and females,
      sex-specific vaccination schedules may be indicated. We systematically reanalysed
      childhood vaccination studies conducted in The Netherlands for sex-differences in
      IgG-responses. To assess the impact of potential sex-differences in IgG
      responses, we explored sex-differences in vaccine failure/effectiveness and
      reactogenicity. METHODS: Six studies with IgG-measurements for 1577 children
      following infant pneumococcal (PCV7/PCV10/PCV13) and/or DTaP-IPV-Hib(-HepB)
      vaccinations, or the pre-school DTaP-IPV booster were included. We performed one
      stage individual participant data meta-analyses per time-point of the effect of
      sex on IgG levels against pneumococcal serotypes, diphtheria toxoid, tetanus
      toxoid, pertussis Ptx/FHA/Prn and Hib-PRP using linear mixed models. Using
      existing study data, we compared reactogenicity after PCV7/PCV10 and DTaP-IPV
      Hib(-HepB) vaccination in girls and boys. Vaccine failure/effectiveness was
      compared between girls and boys for invasive pneumococcal disease (IPD), invasive
      Hib disease and pertussis using notification data. RESULTS: For pneumococcal
      vaccination, the geometric mean concentration ratio of IgG levels in girls versus
      boys pooled across serotypes was 1.15 (95%CI 0.91-1.45) 1 month following the
      primary series, 1.16 (1.02-1.32) at age 8 months, 1.12 (1.02-1.23) pre-booster
      (age 11 months) and 0.99 (0.89-1.10) post-booster (age 12 months). Diphtheria
      toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP IgG levels did not
      differ between girls and boys, except for Hib post-booster (1.24; 95%CI 1.01
      1.52) and tetanus before pre-school booster (0.71; 0.53-0.95). We found no
      difference between boys and girls in reactogenicity at age 4 or 11 months or in
      vaccine failure/effectiveness for IPD, invasive Hib disease or pertussis.
      CONCLUSION: For most vaccine antigens investigated, there were no consistent
      differences in vaccine-induced IgG levels. Vaccine-induced pneumococcal IgG
      levels were slightly higher in girls, but only between the primary series and the
      11-month booster. These results, along with similar reactogenicity and vaccine
      failure/effectiveness, support the uniform infant vaccination schedule in the
      Dutch national immunisation programme.

PMID- 29223485
TI  - Preventive effect of anti-VacA egg yolk immunoglobulin (IgY) on Helicobacter
      pylori-infected mice.
AB  - BACKGROUND: Helicobacter pylori, a gram-negative bacterium, is the causative
      agent of gastric disorders and gastric cancer in the human stomach. Vacuolating
      cytotoxin A (VacA) is among the multi-effect protein toxins released by H. pylori
      that enables its persistence in the human stomach. METHODS: To evaluate the
      effect of anti-VacA egg yolk immunoglobulin (anti-VacA IgY) on H. pylori
      infection, a highly specific anti-VacA IgY was produced from egg yolks of hens
      immunized with a mixture of two purified recombinant VacAs. Female C57BL/6 mice
      were supplemented anti-VacA IgY daily with drinking water for 2 weeks before and
      4 weeks after H. pylori ATCC 43504 inoculation. Anti-VacA IgY recognized both
      native and denatured structures of VacA by enzyme-linked immunosorbent assay and
      immunoblotting analyses, respectively. RESULTS: Oral administration of anti-VacA
      IgYs significantly (p < .05) reduced the serum levels of anti-H. pylori
      antibodies compared to those in the H. pylori-infected, untreated group. The
      reduction in the immune response was accompanied by a significant (p < .05)
      decrease in eosinophilic infiltration of the stomach in anti-VacA IgY treated
      group compared to other groups. Concomitantly, H. pylori-induced histological
      changes and H. pylori antigen-positivity in gastric tissues were decreased
      significantly (p < .05) in anti-VacA IgY treated group similar to the control
      group. CONCLUSIONS: Oral administration of anti-VacA IgY is correlated with a
      protective effect against H. pylori colonization and induced histological changes
      in gastric tissues. Our experimental study has proved that it is expected to be a
      new drug candidate of Hp infection by further study.

PMID- 29223486
TI  - Cost-effectiveness of rotavirus vaccination in Ghana: Examining impacts from 2012
      to 2031.
AB  - BACKGROUND: Diarrhea causes about 10% of all deaths in children under five years
      globally, with rotavirus causing about 40% of all diarrhea deaths. Ghana
      introduced rotavirus vaccination as part of routine immunization in 2012 and it
      has been shown to be effective in reducing disease burden in children under five
      years. Ghana's transition from low to lower-middle income status in 2010 implies
      fewer resources from Gavi as well as other major global financing mechanisms.
      Ghana will soon bear the full cost of vaccines. The aim of this study was to
      estimate the health impact, costs and cost-effectiveness of rotavirus vaccination
      in Ghana from introduction and beyond the Gavi transition. METHODS: The TRIVAC
      model is used to estimate costs and effects of rotavirus vaccination from 2012
      through 2031. Model inputs include demographics, disease burden, health system
      structure, health care utilization and costs as well as vaccine cost, coverage,
      and efficacy. Model inputs came from local data, the international literature and
      expert consultation. Costs were examined from the health system and societal
      perspectives. RESULTS: The results show that continued rotavirus vaccination
      could avert more than 2.2 million cases and 8900 deaths while saving US$6 to US$9
      million in costs over a 20-year period. The net cost of vaccination program is
      approximately US$60 million over the same period. The societal cost per DALY
      averted is US$238 to US$332 with cost per case averted ranging from US$27 to
      US$38. The cost per death averted is approximately US$7000. CONCLUSION: The
      analysis shows that continued rotavirus vaccination will be highly cost
      effective, even for the period during which Ghana will assume responsibility for
      purchasing vaccines after transition from Gavi support.

PMID- 29223487
TI  - Implementing a province-wide mandatory vaccinate-or-mask policy at healthcare
      facilities in British Columbia, Canada.
AB  - OBJECTIVES: In 2012, British Columbia (BC) became the first Canadian province to
      implement an influenza prevention policy requiring healthcare workers (HCW) to
      either be vaccinated annually against influenza or wear a mask in patient care
      areas during the influenza season. This study describes an evaluation of
      influenza policy implementation processes and identifies supports and challenges
      related to successful policy implementation at the level of healthcare
      facilities, during the second policy year (2013/14). METHODS: Implementation
      leaders from 262 long-term care (LTC) and acute care facilities, mostly in three
      of BC's five regional Health Authorities, were invited to participate in an
      online survey following the 2013/14 influenza season. Descriptive quantitative
      and qualitative analyses identified common and effective strategies for improving
      vaccination coverage and policy compliance. RESULTS: A total of 127 respondents
      completed the survey on behalf of 33 acute care and 99 LTC facilities,
      representing 36% of acute care and 27% of LTC facilities in BC. Respondents
      agreed that the policy was successfully implemented at 89% of facilities, and
      implementation was reported to be easy at 52% of facilities. The findings
      elaborate on communication and leadership strategies, campaign logistics and
      enforcement approaches involved in policy implementation. CONCLUSION:
      Implementation of a vaccinate-or-mask influenza policy is complex. This study
      provides insight for other jurisdictions considering implementing such a policy
      and offers practical recommendations for facilities and health authorities.

PMID- 29223488
TI  - Oral administration of PLGA-encapsulated CpG ODN and Campylobacter jejuni lysate
      reduces cecal colonization by Campylobacter jejuni in chickens.
AB  - Campylobacter jejuni (C. jejuni) is a major cause of bacterial food-borne illness
      in humans. It is considered a commensal organism of the chicken gut and infected
      chickens serve as a reservoir and shed bacteria throughout their lifespan.
      Contaminated poultry products are considered the major source of infection in
      humans. Therefore, to reduce the risk of human campylobacteriosis, it is
      essential to reduce the bacterial load in poultry products. The present study
      aimed to evaluate the protective effects of soluble and PLGA-encapsulated
      oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (E-CpG ODN) as
      well as C. jejuni lysate as a multi-antigen vaccine against colonization with C.
      jejuni. The results revealed that oral administration of a low (5 ug) or high (50
      ug) dose of CpG resulted in a significant reduction in cecal C. jejuni
      colonization by 1.23 and 1.32 log10 (P < .05) in layer chickens, respectively,
      whereas E-CpG significantly reduced cecal C. jejuni colonization by 1.89 and 1.46
      log10 in layer and broiler chickens at day 22 post-infection (slaughter age in
      broilers), respectively. Similar patterns were observed for C. jejuni lysate;
      oral administration of C. jejuni lysate reduced the intestinal burden of C.
      jejuni in layer and broiler chickens by 2.24 and 2.14 log10 at day 22 post
      infection, respectively. Moreover, the combination of E-CpG and C. jejuni lysate
      reduced bacterial counts in cecal contents by 2.42 log10 at day 22 post-infection
      in broiler chickens. Anti-C. jejuni IgG antibody (Ab) titers were significantly
      higher for broiler chickens receiving a low or high dose of E-CpG or a low dose
      of C. jejuni lysate than for chickens receiving the placebo. Furthermore, a
      positive correlation was observed between serum IgG Ab titers and cecal counts of
      C. jejuni in these groups. These findings suggest that PLGA-encapsulated CpG or
      C. jejuni lysate could be a promising strategy for control of C. jejuni in
      chickens.

PMID- 29223489
TI  - Platelet mass index can be a reliable marker in predicting the prognosis of
      retinopathy of prematurity in very preterm infants.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a proliferative vitreoretinopathy
      resulting from vascular defect of the retina. The present study evaluates
      platelets, which are involved in VEGF storage, transport and release, and their
      functions with regard to the prognosis of the disease. The objective was to
      suggest a simple minimal invasive method that will facilitate the management of
      the disease and help clinicians in predicting the prognosis. METHODS: In this
      single center, retrospective, case-control study, we included a control group
      consisting of very preterm newborns (n = 83) at risk of ROP and a laser
      photocoagulation group including infants (n = 63) who received laser therapy
      during their follow-up examinations. The employed assessments included platelet
      counts and platelet mass index (PMI) which provide guidance in understanding
      platelet activity. In doing so, consideration was given to the first and second
      phases of ROP. The accuracy of prognostication was assessed with receiver
      operating characteristic analyses. RESULTS: The study groups did not differ
      statistically significantly by platelet count during the first and second phases
      of ROP (p > 0.05) nor were the PMI measurements statistically significantly
      different between the study groups during the first phase of the disease (p >
      0.05). PMI values of the study groups, however, differed significantly in the
      second phase of ROP (p < 0.05). CONCLUSION: The present study found a significant
      difference between the two groups in PMI measurements which reflect increased
      VEGF levels during the neovascularization phase, which underlies the disease.
      This conclusion demonstrated that monitoring the PMI values in newborns at risk
      of ROP can be considered to be a minimally invasive method that by changing the
      retinal examination procedure in use today which is rather troublesome for both
      the physician and the newborn, can provide facilities in monitoring the disease
      for both the physician and the newborn.

PMID- 29223490
TI  - Implicit causality bias in adults with traumatic brain injury.
AB  - INTRODUCTION: Individuals with moderate or severe traumatic brain injury often
      experience impairments in pragmatic language functions. Pragmatic language has
      been studied primarily in connected language genres such as narratives. It may
      be, however, that individuals with traumatic brain injury also miss microscopic
      cues, such as social cues embedded in single word meanings or sentence structure.
      The current study examined one type of sentence-level pragmatic language cue:
      implicit causality bias. Implicit causality bias is the attribution of an
      interpersonal transitive verb action to either the subject noun phrase or object
      noun phrase of a sentence, and is an inherent property of English-language verbs.
      METHOD: In this study, 19 adults with traumatic brain injury and 18 typical
      adults were asked to provide sensible and spontaneous completions to 96 sentence
      fragments. Each fragment contained one interpersonal transitive verb and two noun
      phrases to which the cause of the verb could be attributed. RESULTS: Adults with
      traumatic brain injury showed significantly less implicit causality bias than
      typical adults, and also made more errors in assigning the causality of a clause.
      CONCLUSIONS: These results challenge assumptions regarding intact implicit
      processing in adults with traumatic brain injury, and reveal mechanisms by which
      communication could fail in everyday social interactions.

PMID- 29223491
TI  - A study of VHI scores and acoustic features in street vendors as occupational
      voice users.
AB  - PURPOSE: to investigate acoustic features of phonation and perception of voice
      handicap in street vendors. METHODS: Eighty-eight participants (44 street
      vendors, 44 controls) were recruited. The mean age of the group was 38.9+/-16.0
      years (range: 20-78 years). Scores of the Arabic version of the Voice Handicap
      Index (VHI-Arab) were used for analysis. Acoustic measures of fundamental
      frequency (F0), jitter, shimmer, and signal-to-noise ratio (SNR) were also
      analyzed. RESULTS: Analysis showed a significant difference between street
      vendors and controls in the total score of the VHI-Arab (p<0.001) as well as
      scores of all three VHI-Arab subsections: functional (p<0.001), physical
      (p<0.001), and emotional (p=0.025). Weak correlations were found among all of the
      VHI scores and acoustic measures (-0.219<= r<=0.355), except for SNR where a
      moderate negative correlations were found (r=-0.555; -0.4) between the VHI
      (physical and total) scores and SNR values. Significant differences also were
      found in F0, jitter, and SNR among specific subgroups of street vendors when
      stratified by weekly hours worked (p<0.05), and in jitter (p=0.39) when
      stratified by educational level. CONCLUSIONS: Perception of voice handicap and a
      possible effect on vocal quality in street vendors were noted. The effect of
      factors, namely work hours and educational level, on voice quality should be
      further studied.

PMID- 29223492
TI  - Young children's family history of stuttering and their articulation, language
      and attentional abilities: An exploratory study.
AB  - PURPOSE: The purpose of this study was to determine whether young children who do
      (CWS) and do not stutter (CWNS) with a positive versus negative family history of
      stuttering differ in articulation, language and attentional abilities and family
      histories of articulation, language and attention related disorders. METHOD:
      Participants were 25 young CWS and 50 young CWNS. All 75 participants' caregivers
      consistently reported a positive or negative family history of stuttering across
      three consecutive time points that were about 8 months apart for a total of
      approximately 16 months. Each participant's family history focused on the same,
      relatively limited number of generations (i.e., participants' parents &
      siblings). Children's family history of stuttering as well as articulation,
      language, and attention related disorders was obtained from one or two caregivers
      during an extensive interview. Children's speech and language abilities were
      measured using four standardized articulation and language tests and their
      attentional abilities were measured using caregiver reports of temperament.
      RESULTS: Findings indicated that (1) most caregivers (81.5% or 75 out 92) were
      consistent in their reporting of positive or negative history of stuttering; (2)
      CWNS with a positive family history of stuttering, compared to those with a
      negative family history of stuttering, were more likely to have reported a
      positive family history of attention deficit/hyperactivity disorder (ADHD), and
      (3) CWNS with a positive family history of stuttering had lower language scores
      than those with a negative family history of stuttering. However, there were no
      such significant differences in family histories of ADHD and language scores for
      CWS with a positive versus negative family history of stuttering. In addition,
      although 24% of CWS versus 12% of CWNS's caregivers reported a positive family
      history of stuttering, inferential analyses indicated no significant differences
      between CWS and CWNS in relative proportions of family histories of stuttering.
      CONCLUSION: Finding that a relatively high proportion (i.e., 81.5%) of caregivers
      consistently reported a positive or negative family history of stuttering across
      three consecutive time points should provide some degree of assurance to those
      who collect such caregiver reports. Based on such consistent caregiver reports,
      linguistic as well as attentional vulnerabilities appear associated with a
      positive family history of stuttering, a finding that must await further
      empirical study for confirmation or refutation.

PMID- 29223493
TI  - Comparison of Adjuvant Radiation Therapy Before or After Artificial Urinary
      Sphincter Placement: A Multi-Institutional, Retrospective Analysis.
AB  - OBJECTIVE: To determine if the timing of radiation therapy on artificial urinary
      sphincter (AUS) impacts complication rates, revision rates, and number of pads
      per day after placement. METHODS: A retrospective review was conducted of men
      with prostate cancer who underwent AUS placement and radiation therapy between
      1987 and 2016. RESULTS: Of 306 men, 292 (95.4%) received radiation before AUS
      placement (group 1) and 14 (4.6%) received radiation after AUS placement (group
      2). Median follow-up was 30 months after AUS placement. Group 1 had 32 of 292
      (11.0%) patients suffer from erosion, compared with 0 of 14 (0.0%) patients in
      group 2 (P = .191). None of the patients in group 2 had infection or mechanical
      failure. The number of patients who received revision in group 1 was 91 of 292
      (31.2%) and in group 2 was 2 of 14 (14.3%) (P = .180). The number of pads used
      per day in group 1 before and after AUS placement was 5.24 +/- 3.12 and 1.13 +/-
      1.31, respectively (P <.001). In group 2, the number of pads used per day before
      and after AUS placement was 6.09 +/- 1.97 and 1.53 +/- 0.99, respectively (P
      <.001). There was no significant difference in the average number of
      postoperative pads used per day between group 1 and group 2 (P = .907).
      CONCLUSION: The timing of radiation therapy does not appear to significantly
      affect complication rates or urinary continence, as measured in pads used after
      AUS placement. This multi-institutional retrospective analysis showed similar
      erosion and revision rates when radiation occurred after AUS placement and
      demonstrates preliminary safety and feasibility of the administration of
      radiation after AUS placement.

PMID- 29223494
TI  - Dental functional morphology predicts the scaling of chewing rate in mammals.
AB  - How food intake and mastication scale to satisfy the metabolic needs of mammals
      has been the subject of considerable scientific debate. Existing theory suggests
      that the negative allometric scaling of metabolic rate with body mass is
      compensated by a matching allometric scaling of the chewing rate. Why empirical
      studies have found that the scaling coefficients of the chewing rate seem to be
      systematically smaller than expected from theory remains unknown. Here we explain
      this imparity by decoupling the functional surface area of teeth from overall
      surface area. The functional surface area is relatively reduced in forms
      emphasizing linear edges (e.g., lophodont) compared with forms lacking linear
      structures (e.g., bunodont). In forms with reduced relative functional surface,
      the deficit in food processed per chew appears to be compensated for by increased
      chewing rate, such that the metabolic requirements are met. This compensation
      accounts for the apparent difference between theoretically predicted and observed
      scaling of chewing rates. We suggest that this reflects adaptive functional
      evolution to plant foods with different fracture properties and extend the theory
      to incorporate differences in functional morphology.

PMID- 29223495
TI  - Estimation of spinal joint centers from external back profile and anatomical
      landmarks.
AB  - Defining a subject-specific model of the human body is required for motion
      analysis in many fields, such as in ergonomics and clinical applications.
      However, locating internal joint centers from external characteristics of the
      body still remains a challenging issue, in particular for the spine. Current
      methods mostly require a set of rarely accessible (3D back or trunk surface) or
      operator dependent inputs (large number of palpated landmarks and landmarks-based
      anthropometrics). Therefore, there is a need to provide an alternative way to
      estimate joint centers only using a limited number of easily palpable landmarks
      and the external back profile. Two methods were proposed to predict the spinal
      joint centers: one using only 6 anatomical landmarks (ALs) (2 PSIS, T8, C7, IJ
      and PX) and one using both 6 ALs and the external back profile. Regressions were
      established using the X-ray based 3D reconstructions of 80 subjects and evaluated
      on 13 additional subjects of variable anthropometry. The predicted location of
      joint centers showed an average error 9.7 mm (+/-5.0) in the sagittal plane for
      all joints when using the external back profile. Similar results were obtained
      without using the external back profile, 9.5 mm (+/-5.0). Compared to other
      existing methods, the proposed methods offered a more accurate prediction with a
      smaller number of palpated points. Additional methods have to be developed for
      considering postures other than standing, such as a sitting position.

PMID- 29223496
TI  - Multi-modal imaging investigation of anterior cingulate cortex cytoarchitecture
      in neurodevelopment.
AB  - Multi-modal imaging may improve our understanding of the relationship between
      cortical morphology and cytoarchitecture. To this end we integrated the analyses
      of several magnetic resonance imaging (MRI) and spectroscopy (MRS) metrics within
      the anterior cingulate cortex (ACC). Considering the ACCs role in
      neurodevelopmental disorders, we also investigated the association between
      neuropsychiatric symptoms and the various metrics. T1 and diffusion-weighted MRI
      and 1H-MRS (ACC voxel) data along with phenotypic information were acquired from
      children (8-12 years) with various neurodevelopmental disorders (n=95) and
      healthy controls (n=50). From within the MRS voxel mean diffusivity (MD) of the
      grey matter fraction, intrinsic curvature (IC) of the surface and concentrations
      of creatine, choline, glutamate, N-acetylaspartate and myo-inositol were
      extracted. Linear models were used to investigate if the neurochemicals predicted
      MD and IC or if MD predicted IC. Finally, measures of various symptom severities
      were included to determine the influence of symptoms of neurodevelopmental
      disorders. All five neurochemicals inversely predicted MD (all puncorrected<0.04,
      beta=0.23-0.36). There was no association between IC and MD or IC and the
      neurochemicals (all p>0.05). Severity of autism symptoms related positively to MD
      (puncorrected=0.002, beta=0.39). Our findings support the notion that the
      neurochemicals relate to cytoarchitecture within the cortex. Additionally, we
      showed that autism symptoms across participants relate to the ACC
      cytoarchitecture.

PMID- 29223497
TI  - Older teen attitudes toward birth control access in pharmacies: a qualitative
      study.
AB  - OBJECTIVES: To examine adolescent attitudes toward accessing contraception
      through a new pharmacist prescribing model in the State of California. STUDY
      DESIGN: In-depth telephone interviews were conducted in summer 2015 with 30
      females ages 18 to 19 in California. Participants were recruited using a social
      media advertisement. Semi-structured interviews utilized open-ended questions to
      understand teens' experiences with pharmacies, experiences obtaining
      contraception, and views on pharmacist prescribing of contraception. Responses
      were transcribed and qualitatively analyzed using an independent-coder method to
      identify salient themes. RESULTS: Participants were ethnically diverse and
      primarily living in suburban areas. All participants had completed high school
      and many had completed one year of college. Nearly all participants were
      supportive of California's new law allowing pharmacist prescribing of
      contraception. Thematic analyses revealed that while participants were satisfied
      with traditional service providers and valued those relationships, they
      appreciated the benefit of increased access and convenience of going directly to
      a pharmacy. Participants expected increased access to contraception in pharmacies
      would lead to both personal and societal benefits. They expressed concerns
      regarding parental involvement, as well as confidentiality in the pharmacy
      environment and with insurance disclosures. CONCLUSION: Older teens in California
      are very supportive of pharmacies and pharmacists as direct access points for
      contraception, but confidentiality concerns were noted. Policy makers and
      pharmacies can incorporate study findings when designing policies, services, and
      physical pharmacy spaces to better serve teens. Further research is warranted
      after pharmacies implement this new service to assess teen utilization and
      satisfaction as well as outcomes. IMPLICATION STATEMENT: Several states recently
      passed legislation enabling pharmacists to prescribe contraception and other
      states are considering similar legislation. Older teens are interested in this
      additional method of contraceptive access and understanding their perspectives
      can help guide implementation by states and in individual pharmacies.

PMID- 29223498
TI  - Heparin-fibronectin interactions in the development of extracellular matrix
      insolubility.
AB  - During extracellular matrix (ECM) assembly, fibronectin (FN) fibrils are
      irreversibly converted into a detergent-insoluble form which, through FN's multi
      domain structure, can interact with collagens, matricellular proteins, and growth
      factors to build a definitive matrix. FN also has heparin/heparan sulfate (HS)
      binding sites. Using HS-deficient CHO cells, we show that the addition of soluble
      heparin significantly increased the amount of FN matrix that these cells
      assemble. Sulfated HS glycosaminoglycan (GAG) mimetics similarly increased FN
      assembly and demonstrated a dependence on GAG sulfation. The length of the
      heparin chains also plays a role in assembly. Chains of sufficient length to bind
      to two FN molecules gave maximal stimulation of assembly whereas shorter heparin
      had less of an effect. Using a decellularized fibroblast matrix for proteolysis,
      detergent fractionation, and mass spectrometry, we found that the predominant
      domain within insoluble fibril fragments is FN's major heparin-binding domain
      HepII (modules III12-14). Multiple HepII domains bind simultaneously to a single
      heparin chain in size exclusion chromatography analyses. We propose a model in
      which heparin/HS binding to the HepII domain connects multiple FNs together to
      facilitate the formation of protein interactions for insoluble fibril assembly.

PMID- 29223499
TI  - A comparison of standard versus low dose heparin on access-related complications
      after coronary angiography through radial access: A meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Transradial access (TRA) is preferred for coronary angiography (CA)
      or percutaneous coronary intervention due to reduced access-related
      complications, and mortality especially for patients with ST elevation myocardial
      infarction. Radial artery occlusion (RAO) is a known complication of TRA, and
      precludes its use as a future access site, conduit for coronary artery bypass
      grafting or for hemodialysis fistula placement. Although a standard dose (SD)
      heparin of 5000 Units is used during TRA, the risks of RAO and hematoma compared
      to lower dose (LD) remain unclear. To compare the risks of RAO and hematoma using
      SD vs. LD heparin after CA through TRA, we performed a meta-analysis of
      randomized controlled trials (RCT). METHODS: We searched PubMed, EMBASE, CINAHL
      and CENTRAL for RCTs since inception through 06/30/2017 and used random effects
      model for analysis. The outcomes analyzed were RAO, hematoma formation and radial
      artery compression time (RACT). RESULTS: We identified a total of 6 RCTs with a
      total of 2239 patients. SD heparin resulted in a trend toward a lower risk of RAO
      [4.2% vs. 10.7%; risk ratio (RR): 0.40, 95% confidence interval (CI): 0.16-1.0;
      P=0.05], a trend toward increased risk of hematoma [2.2% vs. 1.1%; 1.83 (0.91
      3.66); P=0.09], and a longer duration of RACT [mean difference: 9.64min (4.01
      15.28); P=0.0008] compared to LD. CONCLUSIONS: The current meta-analysis showed a
      trend towards reduction in the risk of RAO with the use of standard dose heparin.
      Larger randomized trials should explore the appropriate dosing of heparin to
      prevent radial artery occlusion.

PMID- 29223500
TI  - Impact of chronic kidney disease on mortality in adults undergoing balloon aortic
      valvuloplasty.
AB  - BACKGROUND: Balloon aortic valvuloplasty (BAV) is often utilized as a bridge
      prior to surgical or transcatheter aortic valve replacement. Chronic kidney
      disease (CKD) is commonly present in patients with aortic stenosis, however, its
      association with outcomes following BAV has not been well studied. Accordingly,
      we sought to assess the impact of CKD on mortality in adults undergoing BAV.
      METHODS: The Nationwide Inpatient Sample was screened for hospitalizations
      involving adults undergoing BAV from 2006 to 2012. Demographic data and clinical
      history were recorded. Patients were divided into those with and without CKD as a
      documented comorbidity and were compared for adjusted in-hospital mortality risk.
      RESULTS: Among a national cohort of 10,845 adults undergoing BAV, 3842 (35.4%)
      adults had CKD while 7003 (64.6%) did not. Patients with CKD were older, more
      often male, and had higher rates of coronary disease, heart failure, diabetes
      mellitus, hypertension, peripheral artery disease, obesity, obstructive sleep
      apnea, and atrial fibrillation. Adults with CKD undergoing BAV had significantly
      higher in-hospital mortality rates (10.2% vs 6.3%, p=0.0005). In multivariable
      analysis, CKD was independently associated with a nearly 2-fold higher odds of in
      hospital mortality (odds ratio 1.98, 95% confidence interval 1.45-2.70,
      p<0.0001). Other predictors of mortality included presence of atrial fibrillation
      and absence of prior myocardial infarction, hypertension, peripheral arterial
      disease, and smoking. CONCLUSIONS: CKD was independently associated with a nearly
      2-fold higher odds of in-hospital mortality in adults undergoing BAV. Further
      studies are warranted to determine whether preventive interventions can improve
      outcomes in this high-risk population.

PMID- 29223501
TI  - rAsp f3 and rAsp f4 are associated with bronchiectasis in allergic fungal airways
      disease.

PMID- 29223502
TI  - Hydroxyl radical production via NADPH oxidase in rat striatum due to carbon
      monoxide poisoning.
AB  - Severe poisoning induced by carbon monoxide (CO) at 3000 ppm, but not 1000 ppm,
      enhances hydroxyl radical (OH) production in rat striatum, which is greatly
      susceptible to inhibitors of NADPH oxidase (NOX), including diphenyleneiodonium
      (DPI), but not xanthine oxidase. The quantitative real-time PCR confirmed the
      previous microarray finding that CO at 3000 ppm, but not 1000 ppm, enhanced mRNA
      expression of dual oxidase 2 (DUOX2), but not DUOX1, in rat striatum, both of
      which are NOX family members producing reactive oxygen species. However, the
      protein levels of DUOX2 and DUOX1 were decreased by 3000 ppm CO. The CO-induced
      OH production was resistant to chelerythrine and SB230580, inhibitors of protein
      kinase C and p38MAPK, respectively, which are reported to mediate activation of
      DUOX1 and DUOX2, respectively. Deprivation of Ca2+, which is required for
      activation of both DUOXs, failed to suppress the CO-induced OH production. The CO
      induced OH production was strongly suppressed by EHT1864, an inhibitor of Rac
      (Ras-related C3 botulinum toxin substrate), which is a factor for activation of
      NOX1, NOX2 and NOX3 (the role of Rac on Nox3 activation is controversial) as much
      as that was suppressed by DPI. In addition, EHT1864 in combination with DPI
      further suppressed the CO-induced OH production. There were no significant
      changes in the protein levels of NOX1 through NOX4 and Rac1. It is likely that
      the CO-induced OH production is mediated through the activation of Rac-dependent
      NOX enzymes, such as Nox1, Nox2, and Nox3.

PMID- 29223503
TI  - Multiple collections of common carp Cyprinus carpio L. semen during the
      reproductive period and its effects on sperm quality.
AB  - Multiple collections of semen during the reproductive period of the common carp
      Cyprinus carpio L. were used to analyse changes in semen quality. Semen
      collection was performed on June 1 (first collection), 12 (second collection),
      and 19 (third collection) from individual males (n=11) by gentle abdominal
      massage. Semen quantity (semen volume and sperm count), quality (sperm motility
      and sperm viability), as well as seminal plasma parameters (pH of seminal plasma
      and seminal plasma osmotic pressure) and its enzymatic activity, e.g., lactate
      dehydrogenase (LDH) and beta-N-acetylglucosaminidase (beta-NAG) were determined.
      Moreover, for the first time, the percentage of live, dead, and apoptotic sperm,
      as well as the proteolytic activity of seminal plasma, were determined using flow
      cytometry and zymography, respectively, at specific times during the common carp
      reproductive period. The lowest volumes of semen and sperm concentration were
      noted during the first semen collection (June 1). Analysis of computer-assisted
      sperm analysis parameters revealed the greatest sperm motility, sperm velocity,
      as well as amplitude of lateral head displacement, were evident in the third
      collection (June 19). There were no differences in progressively motile sperm,
      movement linearity, wobbling index, and beat cross frequency between the
      different collection times. The lowest percentage of live sperm was found in the
      first collection, although with the passage of time values of this parameter
      increased. Seminal plasma pH and seminal plasma osmotic pressure were at the
      lowest values in the second collection (June 12), which corresponded with the
      lowest concentration of sperm. In the first collection, seminal plasma contained
      the highest values of LDH and beta-NAG activity, whereas there were no
      differences in the proteolytic activity of seminal plasma determined between the
      different collections of semen. The results presented here indicate that during
      the reproductive period, males of common carp produce a large amount of semen of
      moderate quality. Low sperm motility noted in the second collection might be
      explained by a significant increase in sperm production during this period,
      followed by a low seminal plasma pH and high hydration rate. The high LDH and
      beta-NAG activity noted in the first collection of semen may reflect a reduced
      stability of the sperm cell membrane and its viability. The significant
      difference in the percentage of live sperm at June 1 compared to that at June 19
      supports this hypothesis.

PMID- 29223504
TI  - Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN
      translation and/or RNA gain-of-function?
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited
      neurodegenerative disease caused by an expansion of 55-200 CGG repeats located in
      the FMR1 gene. The main clinical and neuropathological features of FXTAS are
      progressive intention tremor and gait ataxia associated with brain atrophy,
      neuronal cell loss and presence of ubiquitin-positive intranuclear inclusions in
      both neurons and astrocytes. At the molecular level, FXTAS is characterized by
      increased expression of FMR1 sense and antisense RNA containing expanded CGG or
      GGC repeats, respectively. Here, we discuss the putative molecular mechanisms
      underlying FXTAS and notably recent reports that expanded CGG and GGC repeats may
      be pathogenic through RAN translation into toxic proteins.

PMID- 29223505
TI  - Pakistan Genetic Mutation Database (PGMD); A centralized Pakistani mutome data
      source.
AB  - The development and advancement of next generation sequencing have not only sped
      up the process of identifying rare variants, but have also enabled scientists to
      explore all variants in a single individual. The Pakistani population has a high
      ratio of first degree consanguinity, which is why it is a rich source for various
      kinds of genetic disorders. Due to the heterogeneous composition of Pakistani
      population, the likelihood of genetic heterogeneity for each disorder is high.
      Therefore, the compilation and organization of such vast genetic data is
      necessary to facilitate access for analysis and interpretation to researchers and
      medical geneticists. The increased research on Pakistani ethnic families for
      disease gene identification has revealed many mutations, which has led us to
      develop a Pakistani mutome database entitled "Pakistan Genetic Mutation Database
      (PGMD)". In PGMD, the medico-genetic information about diseases are mainly
      compiled into Syndromic and Non-syndromic disorders. It is a public database,
      which can be freely accessed from http://www.pakmutation.com. At present, we have
      registered more than 1000 mutations, reported in about 130 different kinds of
      genetic disorders. Practically, PGMD will assist researchers, clinicians, and
      geneticists in genetic counseling and screening of population-specific mutations,
      which will also aid in personalized healthcare.

PMID- 29223506
TI  - Treatment planning considerations for permanent breast seed implant.
AB  - PURPOSE: To determine an optimal planning strategy for permanent breast seed
      implant that minimizes dose heterogeneity without degrading coverage and
      conformity. METHODS AND MATERIALS: A simple model was developed to investigate
      planning strategies incorporating a range of 103Pd seed activities, needle and
      seed spacings, and implants in which seed positions are either restricted to or
      permitted outside of spherical planning target volumes (PTVs). To address more
      realistic target geometries, model parameters were used to retrospectively replan
      a 10-patient cohort in MIM Symphony. RESULTS: We confirm that the current
      clinical modified uniform implantation pattern provides the most favorable dose
      distributions, given the resolution of the template grid and spacer length. We
      show that needle and seed counts for replans with seed placement permitted 0.3 cm
      outside of the PTV are most comparable to clinical preplans, but offer a 13 +/-
      11% average reduction in the VPTV150%. Replans produced with seed placement 0.5
      cm outside of the PTV provide the largest improvement in dose homogeneity, at the
      cost of a slight increase in irradiated volume and an increase in the number of
      needles and seeds. CONCLUSIONS: Implanting seeds beyond the PTV within a 0.3-0.5
      cm margin, and optimizing seed activity on a per patient basis, allows for
      improvement in dose homogeneity. However, these plans require higher needle and
      seed counts and result in a small increase in irradiated volume. Before planning
      recommendations can be made, the implications of these changes must be
      investigated in the context of clinical outcome for permanent breast seed
      implant.

PMID- 29223508
TI  - On the pharmacokinetics of two inhaled budesonide/formoterol combinations in
      asthma patients using modeling approaches.
AB  - Dry powder inhalers containing the budesonide/formoterol combination have
      currently a well-established position among other inhaled products. Even though
      their efficacy mainly depends on the local concentrations of the drug they
      deliver within the lungs, their safety profile is directly related to their total
      systemic exposure. The aim of the present investigation was to explore the
      absorption and disposition kinetics of the budesonide/formoterol combination
      delivered via two different dry powder inhalers in asthma patients. Plasma
      concentration-time data were obtained from a single-dose, crossover
      bioequivalence study in asthma patients. Non-compartmental and population
      compartmental approaches were applied to the available datasets. The non
      compartmental analysis allowed for an initial characterization of the primary
      pharmacokinetic (PK) parameters of the two inhaled drugs and subsequently the
      bioequivalence assessment of the two different dry powder inhalers. The
      population pharmacokinetic analysis further explored the complex absorption and
      disposition characteristics of the two drugs. In case of inhaled FOR, a five
      compartment PK model including an enterohepatic re-circulation process was
      developed. For inhaled BUD, the incorporation of two parallel first-order
      absorption rate constants (fast and slow) for lung absorption in a two
      compartment PK model emphasized the importance of pulmonary anatomical features
      and underlying physiological processes during model development. The role of
      potential covariates on the variability of the PK parameters was also
      investigated.

PMID- 29223507
TI  - Limitations in learning: How treatment verifications fail and what to do about
      it?
AB  - PURPOSE: The purposes of this study were: to provide dialog on why classic
      incident learning systems have been insufficient for patient safety improvements,
      discuss failures in treatment verification, and to provide context to the reasons
      and lessons that can be learned from these failures. METHODS AND MATERIALS:
      Historically, incident learning in brachytherapy is performed via database mining
      which might include reading of event reports and incidents followed by
      incorporating verification procedures to prevent similar incidents. A description
      of both classic event reporting databases and current incident learning and
      reporting systems is given. Real examples of treatment failures based on
      firsthand knowledge are presented to evaluate the effectiveness of verification.
      These failures will be described and analyzed by outlining potential pitfalls and
      problems based on firsthand knowledge. RESULTS: Databases and incident learning
      systems can be limited in value and fail to provide enough detail for physicists
      seeking process improvement. Four examples of treatment verification failures
      experienced firsthand by experienced brachytherapy physicists are described.
      These include both underverification and oververification of various treatment
      processes. CONCLUSIONS: Database mining is an insufficient method to affect
      substantial improvements in the practice of brachytherapy. New incident learning
      systems are still immature and being tested. Instead, a new method of shared
      learning and implementation of changes must be created.

PMID- 29223509
TI  - Neuropeptides and breathing in health and disease.
AB  - Regulatory neuropeptides control and regulate breathing in physiological and
      pathophysiological conditions. While they have been identified in the neurons of
      major respiratory areas, they can be active not only at the central level, but
      also at the periphery via chemoreceptors, vagal afferents, or locally within
      lungs and airways. Some neuropeptides, such as leptin or substance P, are
      respiratory stimulants; others, such as neurotensin, produce variable effects on
      respiration depending on the site of application. Some neuropeptides have been
      implicated in pathological states, such as obstructive sleep apnea or asthma.
      This article provides a concise review of the possible role and functions of
      several selected neuropeptides in the process of breathing in health and disease
      and in lung pathologies.

PMID- 29223510
TI  - Low-grade systemic inflammation: a partial mediator of the relationship between
      diabetes and lung function.
AB  - PURPOSE: An association has been consistently found between diabetes mellitus and
      decreased lung function. We evaluated to what extent low-grade inflammation (as
      measured by the level of high-sensitivity C-reactive protein [hs-CRP]) could
      explain this relationship. METHODS: A sample of 1878 middle-aged adults from the
      cross-sectional Enquete Littoral Souffle Air Biologie Environnement survey
      without self-reported pulmonary and atherosclerosis disease was included. A
      mediation analysis was performed to assess and quantify the hs-CRP level as a
      mediator of the relationship between diabetes and lung function. RESULTS:
      Diabetes was associated with higher hs-CRP level (+22.9%, 95% confidence interval
      = [5.1, 43.6]). The hs-CRP (>4 vs. <=1 mg/L) was associated with lower percentage
      predicted values for the forced expiratory volume in the first second (FEV1) (-4%
      [-6.1, -1.9]) and forced vital capacity (FVC) (-4.4% [-6.5, -2.3]). Diabetes was
      associated with FEV1 (-3.5% [-5.8, -1.3]) and FVC (-3.6% [-5.9, -1.3]). The
      proportion of the effect that is mediated by hs-CRP was 12% [2.4, 37] and 13%
      [3.7, 39.4] for FEV1 and FVC, respectively. CONCLUSIONS: Our results suggest that
      low-grade systemic inflammation could only explain a small part of the
      relationship between diabetes and lung function.

PMID- 29223511
TI  - Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view
      dynamic acquisition and image reconstruction: A feasibility study.
AB  - PURPOSE: We implemented and validated a compressed sensing (CS) based algorithm
      for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from
      sparsely sampled X-ray projections. METHODS: DCE CT imaging of the heart was
      performed on five normal and ischemic pigs after contrast injection. DCE images
      were reconstructed with filtered backprojection (FBP) and CS from all projections
      (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all
      projections (246-view). Myocardial perfusion (MP) measurements with each protocol
      were compared to those with the reference 984-view FBP protocol. RESULTS: Both
      the 984-view CS and 328-view CS protocols were in good agreements with the
      reference protocol. The Pearson correlation coefficients of 984-view CS and 328
      view CS determined from linear regression analyses were 0.98 and 0.99
      respectively. The corresponding mean biases of MP measurement determined from
      Bland-Altman analyses were 2.7 and 1.2ml/min/100g. When only 328 projections were
      used for image reconstruction, CS was more accurate than FBP for MP measurement
      with respect to 984-view FBP. However, CS failed to generate MP maps comparable
      to those with 984-view FBP when only 246 projections were used for image
      reconstruction. CONCLUSION: DCE heart images reconstructed from one-third of a
      full projection set with CS were minimally affected by aliasing artifacts,
      leading to accurate MP measurements with the effective dose reduced to just 33%
      of conventional full-view FBP method. The proposed CS sparse-view image
      reconstruction method could facilitate the implementation of sparse-view dynamic
      acquisition for ultra-low dose CT MP imaging.

PMID- 29223512
TI  - NAFLD: The evolving landscape.

PMID- 29223513
TI  - Study of first electronic transition and hydrogen bonding state of ultra-thin
      water layer of nanometer thickness on an alpha-alumina surface by far-ultraviolet
      spectroscopy.
AB  - The first electronic transition (A~<-X~) and the hydrogen bonding state of an
      ultra-thin water layer of nanometer thickness between two alpha-alumina surfaces
      (0.5-20nm) were studied using far-ultraviolet (FUV) spectroscopy in the
      wavelength range 140-180nm. The ultra-thin water layer of nanometer thickness was
      prepared by squeezing a water droplet (~1MUL) between a highly polished alpha
      alumina prism and an alpha-alumina plate using a high pressure clamp (~4.7MPa),
      and the FUV spectra of the water layer at different thicknesses were measured
      using the attenuated total reflection method. As the water layer became thinner,
      the A~<-X~ bands were gradually shifted to higher or lower energy relative to
      that of bulk water; at thicknesses smaller than 4nm, these shifts were
      substantial (0.1-0.2eV) in either case. The FUV spectra of the water layer with
      thickness <4nm indicate the formation of structured ice-like hydrogen bond (H
      bond) layers for the higher energy shifts or the formation of slightly weaker H
      bond layers as compared to those in the bulk liquid state for lower energy
      shifts. In either case, the H-bond structure of bulk liquid water is nearly lost
      at thicknesses below 4nm, because of steric hydration forces between the alpha
      alumina surfaces.

PMID- 29223514
TI  - Need for integrative thinking to fight against emerging infectious diseases.
      Proceedings of the 5th seminar on emerging infectious diseases, March 22, 2016 -
      current trends and proposals.
AB  - We present here the proceedings of the 5th seminar on emerging infectious
      diseases, held in Paris on March 22nd, 2016, with seven priority proposals that
      can be outlined as follows: encourage research on the prediction, screening and
      early detection of new risks of infection; develop research and surveillance
      concerning transmission of pathogens between animals and humans, with their
      reinforcement in particular in intertropical areas ("hot-spots") via public
      support; pursue aid development and support in these areas of prevention and
      training for local health personnel, and foster risk awareness in the population;
      ensure adapted patient care in order to promote adherence to treatment and to
      epidemic propagation reduction measures; develop greater awareness and better
      education among politicians and healthcare providers, in order to ensure more
      adapted response to new types of crises; modify the logic of governance, drawing
      from all available modes of communication and incorporating new information
      sharing tools; develop economic research on the fight against emerging infectious
      diseases, taking into account specific driving factors in order to create a
      balance between preventive and curative approaches.

PMID- 29223515
TI  - [Patients assaulted in psychiatric institutions: Literature review and clinical
      implications].
AB  - BACKGROUND: The psychiatric ward is a place where all forms of violence are
      treated. Occasionally, this violence involves acts of aggression between patients
      in emergency psychiatric units or hospital wards. Such events can lead to the
      development or worsening of posttraumatic stress disorder. METHODS: To establish
      the context, we first examined the epidemiology data concerning posttraumatic
      stress disorder in psychiatric patients who were frequently exposed to assaults.
      Secondly, we examined the issue of sexual and physical assaults between patients
      receiving treatment in a psychiatric ward. In this context, we studied possible
      occurrence of posttraumatic stress disorder associated with exposure to assaults
      of this kind. RESULTS: In certain cases, potentially traumatic exposure to
      violence was unknown to the medical staff or not taken into consideration. This
      would induce a risk of later development of posttraumatic stress disorder that
      would not be treated during the stay in psychiatry. CONCLUSION: To date, few
      scientific studies have focused on the proportion of patients assaulted by other
      patients during treatment in a psychiatric ward and the subsequent development of
      peritraumatic reactions and/or posttraumatic stress disorder associated with
      these assaults. We know that an insufficient number of public and private health
      institutions report the existence of such facts to the competent authorities.
      Also, a minority of clinicians and caregivers are trained in screening and
      management of trauma victims. Yet, these issues are particularly relevant in the
      scope of public health and health promotion.

PMID- 29223516
TI  - Antimicrobial activity of plazomicin against Enterobacteriaceae-producing
      carbapenemases from 50 Brazilian medical centers.
AB  - Plazomicin is a next-generation aminoglycoside with activity against
      Enterobacteriaceae, including carbapenemase-producing Enterobacteriaceae (CPE).
      The aim of this study was to evaluate the activity of plazomicin against CPE
      (Klebsiella spp., Escherichia coli, Serratia spp., Enterobacter spp., Citrobacter
      spp., Morganella spp., Proteus spp., Providencia spp.) from different Brazilian
      hospitals. A total of 4000 carbapenem-resistant Enterobacteriaceae isolates were
      collected from clinical samples in 50 Brazilian hospitals during 2013-2015. Of
      these, 499 carbapenem-resistant isolates (CLSI criteria) were selected for
      further evaluation via broth microdilution to assess for the activity of
      plazomicin, colistin, tigecycline, meropenem, amikacin, and gentamicin.
      Additionally, the isolates were assessed for the presence of carbapenemase genes
      (blaKPC, blaNDM, blaOXA-48-like, blaIMP, blaBKC, blaGES, and blaVIM) by
      polymerase chain reaction (PCR). When PCR was positive to blaOXA-48-like, blaIMP,
      blaGES, and blaVIM, the carbapenemase genes were sequenced. blaKPC was the most
      prevalent carbapenemase gene found (n=397), followed by blaNDM (n=81), blaOXA-48
      (n=12), and blaIMP-1 (n=3). Other genes were identified in only 1 isolate each:
      blaBKC-1, blaGES-16, blaGES-1, blaOXA-370, and blaVIM-1. One isolate had 2
      carbapenemase genes (blaKPC and blaNDM). Thirty-three percent of the isolates
      were nonsusceptible to colistin, 24% to tigecycline, 97% to meropenem, 51% to
      amikacin, and 81% to gentamicin (via EUCAST criteria). The plazomicin MIC50/90
      was 0.5/64mg/L, with 85% of MICs <=2mg/L and 87% of MICs <=4mg/L. Elevated MICs
      to plazomicin were not associated with a specific carbapenemase or bacterial
      species. The MICs of plazomicin against CPE were lower than those of other
      aminoglycosides. Plazomicin is a promising drug for the treatment of CPE
      infections.

PMID- 29223517
TI  - Combined Spinal Arteriovenous Malformation and Spinal Dysraphism.
AB  - BACKGROUND: Spinal vascular malformations as a group are rare, and coexistence of
      a spinal arteriovenous malformation (AVM) in or around the spinal dysraphism is
      extremely rare. We report 2 cases of combined spinal dysraphism and vascular
      malformations of the spinal cord. CASE DESCRIPTION: The first case was an AVM
      located in a filum terminale lipoma fed by the artery of the filum terminale.
      This case was managed by multiple endovascular embolizations followed by surgery.
      The second case was an AVM located in a lumbar lipomyelocele managed by
      endovascular embolization. These cases illustrate the imaging findings of a rare
      entity and present the diagnostic and therapeutic challenges. CONCLUSIONS:
      Endovascular embolization combined with surgical resection is the most commonly
      used treatment for spinal dysraphism with spinal cord AVM. Careful analysis of
      spinal angiography is necessary owing to the distorted vascular and surgical
      anatomy of the region affected by spinal dysraphism.

PMID- 29223518
TI  - Synchronous Central Nervous System Atypical Teratoid/Rhabdoid Tumor and Malignant
      Rhabdoid Tumor of the Kidney: Case Report of a Long-Term Survivor and Review of
      the Literature.
AB  - BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous
      system (CNS) with synchronous or metachronous extra-CNS disease is a rare
      childhood malignancy with a dismal prognosis. CASE DESCRIPTION: We report a 7
      week-old female with metastatic AT/RT and synchronous malignant rhabdoid tumor of
      the kidney who received an intensive multimodal approach combining surgical
      resection, intrathecal chemotherapy, and high-dose chemotherapy with autologous
      peripheral blood stem cell transplant (PBSCT). She is currently 24 months old
      without any evidence of disease. In addition, we completed an extensive
      literature review of cases with CNS AT/RT and synchronous or metachronous extra
      CNS primary tumors. To date, 31 pediatric cases have been reported, and the
      median overall-survival was 6 months after diagnosis. The only 3 survivors
      received autologous PBSCT, and 2 of these patients had complete resection of
      their CNS tumor. CONCLUSIONS: The rarity of CNS AT/RT with extra-CNS primary
      disease and the lack of standard treatment contribute to its reported dismal
      prognosis. We report a case of a long-term survivor with metastatic AT/RT and
      synchronous extra-CNS primary tumor. Maximal surgical resection, intrathecal
      chemotherapy, and consolidative autologous PBSCT may improve prognosis and avoid
      radiation.

PMID- 29223519
TI  - Efficacy of Reinforced Restriction of Physical Activity on Chronic Subdural
      Hematoma: Prospective Pilot Study.
AB  - BACKGROUND: Chronic subdural hematoma (CSDH) is a common entity in neurosurgical
      practice. However, as a result of the high rate in recurrence, morbidity, and
      mortality for surgical management, conservative management of CSDH is emerging as
      a new treatment strategy. Head trauma is a known risk factor of CSDH and plays as
      an initiator in the genesis of CSDH. We hypothesized that physical activity might
      also play an important role in the progression of an asymptomatic CSDH. METHODS:
      A prospective pilot study aiming to evaluate the efficacy of reinforced
      restriction of physical activity for the management of asymptomatic or mild
      symptomatic CSDH was conducted. Twenty-six patients were enrolled in this study.
      RESULTS: All 26 patients experienced complete resolution of the CSDH ranging from
      32 to 182 days (73.1 +/- 19.6 days) since the initiation of reinforced
      restriction of physical activity. Ages ranged from 43 to 84 years old (64.4 +/-
      9.6 years). No patient experienced recurrence of CSDH during the follow-up.
      CONCLUSIONS: According to our study, physical activity might play a role in the
      progression of CSDH. Further prospective randomized controlled study is warranted
      in stable patients without evident intracranial hypertension and impending
      cerebral herniation.

PMID- 29223520
TI  - Lumbar Microdiscectomy in Obese Patients: A Multicenter Observational Study.
AB  - OBJECTIVE: To evaluate the association between obesity and outcomes after
      microdiscectomy for lumbar disc herniation. METHODS: The primary outcome measure
      was change in Oswestry Disability Index (ODI) at 1 year after surgery. Obesity
      was defined as body mass index (BMI) >=30. Prospective data were retrieved from
      the Norwegian Registry for Spine Surgery. RESULTS: We enrolled 4932 patients,
      4018 nonobese and 914 obese. For patients with complete 1-year follow-up (n =
      3381) the mean improvement in ODI was 31.2 points (95% confidence interval 30.4
      31.9, P < 0.001). Improvement in ODI was 31.4 points in nonobese and 30.1 points
      in obese patients (P = 0.182). Obese and nonobese patients were as likely to
      achieve a minimal clinically important difference (84.2 vs. 82.7%, P = 0.336) in
      ODI (>=10 points improvement). Obesity was identified as a negative predictor for
      ODI improvement in a multiple regression analysis (BMI 30-34.99; P < 0.001, BMI
      >=35; P = 0.029). Obese and nonobese patients experienced similar improvement in
      Euro-Qol-5 scores (0.48 vs. 0.49 points, P = 0.441) as well as back pain (3.7 vs.
      3.5 points, P = 0.167) and leg pain (4.7 vs. 4.8 points, P = 0.654), as measured
      by the Numeric Rating Scale. Duration of surgery was shorter for nonobese
      patients (55.7 vs. 65.3 minutes, P <= 0.001). Nonobese patients experienced fewer
      complications compared with obese patients (6.1% vs. 8.3%, P = 0.017). Obese
      patients had slightly longer hospital stays (2.0 vs. 1.8 days, P = 0.004).
      CONCLUSIONS: Although they had more minor complications, obese individuals
      experienced improvement after lumbar microdiscectomy for lumbar disc herniation
      similar to that of nonobese individuals.

PMID- 29223521
TI  - Risk Factors Analysis for Foot Drop Associated with Lumbar Disc Herniation: An
      Analysis of 236 Patients.
AB  - OBJECTIVES: To identify the risk factors for foot drop in patients with lumbar
      disc herniation (LDH). METHODS: Two hundred thirty-six patients who underwent
      surgery for LDH were retrospectively reviewed. Foot drop was defined as tibialis
      anterior muscle strength of lower than grade 4 by the manual muscle test.
      Possible risk factors, including demographic and radiographic parameters, were
      evaluated by multivariate logistic regression analysis. RESULTS: Fifty-two
      patients (22.9%) suffered from foot drop. Multivariate logistic regression
      analysis revealed that diabetes mellitus, disc calcification, patients who had an
      acute episode or acute-on-chronic episode, and patients who presented with
      lateral recess or extraforaminal type of disc herniation were at greater risk of
      foot drop. Notably, patients who had a canal occupancy rate of more than 50% were
      at greater risk of foot drop compared with patients who had a canal occupy rate
      of less than 25%. With a 1.0-mm increase in anteroposterior diameter of the index
      spinal canal, the risk of developing foot drop decreased to 51.8% in these
      patients (P < 0.05). CONCLUSIONS: The following factors may affect the
      development of foot drop in patients with LDH: 1) diabetes mellitus; 2) patients
      with an acute episode or acute-on-chronic episode; 3) patients with lateral
      recess or foraminal type of herniation; 4) disc calcification; 5) canal occupancy
      rate greater than 50%; and 6) the anteroposterior diameter of canal. Surgical
      treatments for patients with those risk factors should be implemented positively
      during the follow-up period to reduce possible adverse outcomes.

PMID- 29223522
TI  - Custom-Made Titanium 3-Dimensional Printed Interbody Cages for Treatment of
      Osteoporotic Fracture-Related Spinal Deformity.
AB  - BACKGROUND: Advances in minimally invasive interbody fusion have greatly enhanced
      surgeons' capability to correct adult spinal deformity with reduced morbidity.
      However, the feasibility of such approaches is limited in patients with previous
      osteoporotic fractures as the resultant vertebral deformity renders the end plate
      geometry incongruous with conventional interbody implants. Current 3-dimensional
      (3D) printing technology offers a novel solution by fabricating custom-made
      implants tailored to individual anatomy. We present the results of a patient with
      osteoporotic lumbar fractures treated by such technology. CASE DESCRIPTION: A 74
      year-old woman, with previous osteoporotic fractures at L2 and L3 resulting in
      concave deformity of the end plates, presented with intractable radiculopathy
      secondary to lateral recess and foraminal stenosis (L2-3 and L3-4). A minimally
      invasive lateral lumbar interbody fusion at L2-3 and L3-4 was considered
      favorable, but due to the associated vertebral collapse, off-the-shelf implants
      were not compatible with patient anatomy. In silico simulation based on
      preoperative computed tomography (CT) imaging was thus conducted to design
      customized cages to cater for the depressed recipient end plates and vertebral
      loss. The design was converted to implantable titanium cages through 3D additive
      manufacturing. At surgery, a tight fit between the implants and the targeted disk
      space was achieved. Postoperative CT scan confirmed excellent implant-end plate
      matching and restoration of lost disk space. The patient began to ambulate from
      postoperative day 1 and at 6-month follow-up resolution of radicular symptoms and
      CT evidence of interbody fusion were recorded. CONCLUSIONS: 3D-printed custom
      made interbody cages can help overcome the difficulties in deformity correction
      secondary to osteoporotic fractures.

PMID- 29223523
TI  - Effect of Smoking Status on Successful Arthrodesis, Clinical Outcome, and
      Complications After Anterior Lumbar Interbody Fusion (ALIF).
AB  - BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a surgical technique
      indicated for the treatment of several lumbar pathologies. Smoking has been
      suggested as a possible cause of reduced fusion rates after ALIF, although the
      literature regarding the impact of smoking status on lumbar spine surgery is not
      well established. This study aims to assess the impact of perioperative smoking
      status on the rates of perioperative complications, fusion, and adverse clinical
      outcomes in patients undergoing ALIF surgery. METHODS: A retrospective analysis
      was performed on a prospectively maintained database of 137 patients, all of whom
      underwent ALIF surgery by the same primary spine surgeon. Smoking status was
      defined by the presence of active smoking in the 2 weeks before the procedure.
      Outcome measures included fusion rates, surgical complications, Short-Form 12,
      and Oswestry Disability Index. RESULTS: Patients were separated into nonsmokers
      (n = 114) and smokers (n = 23). Univariate analysis demonstrated that the
      percentage of patients with successful fusion differed significantly between the
      groups (69.6% vs. 85.1%, P = 0.006). Pseudarthrosis rates were shown to be
      significantly associated with perioperative smoking. Results for other
      postoperative complications and clinical outcomes were similar for both groups.
      On multivariate analysis, the rate of failed fusion was significantly greater for
      smokers than nonsmokers (odds ratio 37.10, P = 0.002). CONCLUSIONS: The rate of
      successful fusion after ALIF surgery was found to be significantly lower for
      smokers compared with nonsmokers. No significant association was found between
      smoking status and other perioperative complications or adverse clinical
      outcomes.

PMID- 29223524
TI  - Gamma Knife Stereotactic Radiosurgery for Nonvestibular Cranial Nerve
      Schwannomas.
AB  - BACKGROUND: Nonvestibular cranial schwannomas represent a rare type of benign
      intracranial tumor. Few studies have evaluated the use of stereotactic
      radiosurgery (SRS) as a primary management option for these lesions. We performed
      a retrospective review of our institution's experience focusing on efficacy with
      regard to tumor control and clinical symptom stabilization as well as treatment
      safety. METHODS: Patients were included if they underwent at least 1 SRS
      procedure for a nonvestibular schwannoma and had at least 6 months of available
      imaging follow-up. Demographic, SRS dose planning, clinical, and imaging data
      were collected from chart reviews of treated patients. chi2 and Kaplan-Meier
      analyses were performed. RESULTS: Between 2004 and 2016, 35 schwannomas were
      treated in 34 patients. Median follow-up was 48 months. Median age at time of
      treatment was 51 years. Three patients had neurofibromatosis 2. Schwannoma
      location was trigeminal (57%), facial (20%), jugular foramen (14%), abducens
      (6%), and trochlear (3%). Median margin dose delivered was 13 Gy. The 5-year and
      10-year tumor control rates were 94.4% and 88.5%, respectively. Presenting
      clinical symptoms stabilized or improved in 79% of cases after radiosurgery, and
      new or worsening symptoms were seen in 21%. CONCLUSIONS: SRS is a safe and
      effective modality for treatment of nonvestibular cranial nerve schwannomas.

PMID- 29223525
TI  - Rare Thymoma Metastases to the Spine: Case Reports and Review of the Literature.
AB  - BACKGROUND: We report a series of 3 cases of metastatic thymoma to the spine with
      spinal cord compression. An extensive literature review of thymic metastases to
      the spine was completed to provide a comprehensive appraisal of current
      prognostic indicators and potential treatment algorithms to help guide clinicians
      in treatment management. CASE DESCRIPTIONS: Between 2000 and 2017, 3 patients
      received diagnoses of thymic metastases to the spine at our institution.
      Metastasis presentation occurred from 2 to 8 years after the initial diagnosis
      with thymic cancer. All 3 patients presented with signs and symptoms of spinal
      cord/cauda equina compression, and underwent surgical intervention. Postoperative
      treatments varied among all 3 patients, 1 receiving chemotherapy, another
      undergoing radiation, and the third having had no further treatment because of
      extensive systemic disease. CONCLUSIONS: Upon review of the literature, 16 case
      reports/series described 28 total patients with spine metastases secondary to
      thymoma/thymic carcinoma. The presentations varied widely, including age,
      neurologic deficits, time from initial diagnosis to metastasis, and histologic
      grading. The only widely accepted prognostic factor is completeness of tumor
      resection, whereas clinical staging, histologic type, or both may also have
      prognostic value. Thus, gross total resection and spinal decompression should be
      prioritized in cases of surgical intervention. Chemotherapy and radiotherapy are
      generally recommended. However, given the lack of standardized treatment
      algorithms, individualized regimens should be formulated on a case-specific
      basis.

PMID- 29223526
TI  - Spontaneous Spinal Arthrodesis in Stand-Alone Percutaneous Pedicle Screw Fixation
      Without in Situ Fusion in Patients With Lumbar Segmental Instability: Long-Term
      Clinical, Radiologic, and Functional Outcomes.
AB  - BACKGROUND: No study to date has established how commonly spontaneous fusion
      occurs after stand-alone percutaneous pedicle screw fixation in adult population.
      In this retrospective single-center study, we investigated the effectiveness,
      long-term solidity and safety of stand-alone percutaneous pedicle screw fixation
      without in situ fusion and the influence of presence or absence of fusion on the
      clinical outcome of patients with low-grade lumbar segmental instability.
      METHODS: Eighty-eight patients with symptomatic low-grade spondylolisthesis were
      treated with posterior stand-alone percutaneous pedicle screw fixation without
      bone graft. Radiographic evaluation was used to determine if spontaneous fusion
      or absence of fusion was present. The solid fusion and absence of fusion groups
      were analyzed clinically (visual analog scale and Oswestry Disability Index) and
      with a validated self-administered questionnaire. RESULTS: The average duration
      of follow-up was 70.5 months (range, 48-120 months). Radiologic signs of
      spontaneous fusion were present in 45.5% of the cohort and absent in 54.5%.
      Clinical outcome was excellent to good in 73.8% of the cohort (in 70.9% of cases
      with spontaneous fusion and in 67.5% of cases with absence of fusion). No
      significant differences in visual analog scale scores for residual back and lower
      limb pain between the 2 groups were seen at the final follow-up. At the final
      follow-up, 5 of 88 patients (5.6%) underwent revision surgery. CONCLUSIONS:
      Percutaneous pedicle screw fixation offers several advantages that help minimize
      approach-related morbidity, while achieving similar clinical outcome as seen with
      more traditional invasive procedures. A solid fixation without bone graft
      provides long-term clinical benefits. In our patients, the appearance of a
      spontaneous solid fusion and the absence of fusion after stand-alone pedicle
      screw fixation were correlated with similar improved clinical outcomes at long
      term follow-up.

PMID- 29223527
TI  - Low doses of prenatal ethanol exposure and maternal separation alter HPA axis
      function and ethanol consumption in adult male rats.
AB  - Adverse maternal behaviors during pregnancy and unfavorable postnatal experiences
      during development are associated with an increased risk of developing
      psychiatric disorders, as well as, a vulnerability to alcohol addiction in
      adulthood. Here, we examined the effects of combined ethanol exposure during late
      pregnancy and postnatal maternal separation (MS) on HPA responsiveness, anxiety
      behavior and preference for alcohol consumption in adult male rats. Animals
      exposed to both conditions revealed a decrease in blood levels of
      allopregnanolone accompanied by increased anxiety behavior. In addition, basal
      blood levels of corticosterone were markedly decreased in all experimental groups
      while increases in the foot-shock-induced corticosterone levels were more
      pronounced in MS animals. Finally, evaluating EtOH drinking behavior, MS animals
      exhibited a remarkable EtOH preference even at low doses (0.1-1%). Altogether,
      these data suggest that adverse conditions, alone or in combination, may alter
      anxiety-like states as well as modify behavior towards alcohol consumption.

PMID- 29223528
TI  - GLP-1 receptor agonists downregulate aberrant GnT-III expression in Alzheimer's
      disease models through the Akt/GSK-3beta/beta-catenin signaling.
AB  - Alterations of glycoprotein glycans contribute to a wide variety of diseases.
      Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal
      fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N
      acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible
      for synthesizing a bisecting GlcNAc residue, were found highly expressed in the
      brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1)
      and its mimetics showed neuroprotective effects. Here, we confirmed that four
      weeks' treatment of exendin-4 could rescue memory deficits and neuropathological
      changes in APP/PS1 mice. We further explored the underlying mechanism and
      especially the role of GnT-III in it. We demonstrated for the first time that the
      levels of GnT-III and bisecting GlcNAc were increased in APP/PS1 mice and Abeta25
      35-treated PC12 cells, and GLP-1 receptor agonists (GLP-1RA) could downregulate
      aberrant neuronal expression of GnT-III and bisecting GlcNAc. We also found that
      GLP-1RA recovered the phosphorylation levels of Akt (Ser473) and GSK-3beta (Ser9)
      and the levels of beta-catenin in mice and cell models. Furthermore, the results
      indicated that inhibitor LY294002 attenuated these effects of GLP-1RA in PC12
      cells, and beta-catenin siRNA abolished the effect of GLP-1RA on GnT-III. In
      summary, our results suggest that GnT-III plays an important role in AD and GLP
      1RA could downregulate aberrant GnT-III expression through the Akt/GSK-3beta/beta
      catenin signaling pathway in neurons.

PMID- 29223530
TI  - Diet Quality of Chronic Kidney Disease Patients and the Impact of Nutritional
      Counseling.
AB  - OBJECTIVES: The aims of the study were to evaluate the quality of the diet of
      nondialysis-dependent patients with chronic kidney disease and to investigate the
      impact of dietary counseling in the quality of the diet of these patients.
      METHODS: In the cross-sectional analysis, 3-day food records of 100 nondialysis
      dependent patients with chronic kidney disease patients, in the first visit to
      the renal dietitians, were evaluated using the Diet Quality Index (DQI). Under
      reporters were excluded. DQI is comprised by 10 components: 6 are food groups
      (fruits, vegetables, cereals, milk and dairy, meats and eggs, and legumes); 3 are
      nutrients (total fat, sodium, and cholesterol), and the last one is the diet
      variety. Each component is scored from 0 to 10, according to the adequacy of the
      Brazilian dietary guideline, and an overall score ranging from 0 (poor) to 100
      (good) is obtained. In a subsample of 44 patients, a prospective analysis was
      performed to compare the DQI and its components before and after dietary
      counseling. RESULTS: The median DQI score was 68.6 (62.3-75.6; interquartile
      range), which means that most of the patients (92%) had a diet that "needs
      improvement" (DQI between 50 and 80 points). The DQI components with the lowest
      scores (lower adequacy) were sodium (0.0 [0.0-0.9]), dairy (3.9 [2.1-6.0]), and
      vegetables (6.0 [2.8-9.5]), whereas meat/egg, legumes, and cholesterol had the
      highest scores. Vegetables, legumes, and diet variety components were
      significantly lower in the lower tertiles of DQI. After a median follow-up of
      25.0 (17.0-35.8) months comprising 6 (5-10) visits to the dietitian, energy,
      protein, and micronutrients intake were significantly reduced. The dietary
      counseling did not improve the overall DQI (after: 69.0 [69.0-74.8]; P = .95)
      and, a significant reduction in the score of legumes (from 10.0 [2.7-10.0] to 7.8
      [4.7-10.0], P = .00) and diet variety (from 7.0 [5.3-10.0] to 6.0 [4.0-9.0], P =
      .02) components were observed. CONCLUSION: The diet of this cohort of patients
      needs to be improved, particularly regarding vegetables, food variety, and sodium
      intake. Dietary counseling had no positive impact on the diet quality. This
      result highlights the importance of focusing the dietary counseling not simply on
      nutrient or food restriction but providing healthy food choices aiming to improve
      the overall diet quality of the patients.

PMID- 29223529
TI  - Corticosterone impairs gap junctions in the prefrontal cortical and hippocampal
      astrocytes via different mechanisms.
AB  - Increasing evidence has implicated astrocyte pathology in the etiopathology of
      major depressive disorder (MDD). In particular, dysfunction of gap junctions in
      astrocytes is a potential target for MDD treatment. However, the mechanism
      underlying stress-induced dysfunction of gap junctions is still unknown. We
      therefore studied the mechanism of stress-induced dysfunction of gap junctions in
      prefrontal cortical and hippocampal astrocytes. Corticosterone (CORT) was used to
      induce stress conditions; CORT damaged the function of gap junctions, which
      resulted from less distribution of connexin43 (Cx43) on membranes and the
      enhanced phosphorylation of Cx43 at S368. Moreover, CORT downregulated the
      biosynthesis of Cx43 but increased the degradation of Cx43. Interestingly, both
      autophagy and the proteasome system were involved in the degradation of Cx43 in
      prefrontal cortical astrocytes, but only the proteasome system was involved in
      the degradation of Cx43 in hippocampal astrocytes. CORT significantly induced the
      formation of annular gap junction vesicles in prefrontal cortical astrocytes;
      however, Cx43 mainly presented as small dots in the hippocampal astrocytes.
      Furthermore, CORT increased N-Cadherin expression and the interactions of Cx43
      with ZO-1/drebrin in prefrontal cortical astrocytes, but these interactions were
      oppositely modulated in hippocampal astrocytes. In conclusion, this study
      clarified the alternations of the Cx43 life cycle in the prefrontal cortical and
      hippocampal astrocytes exposed to CORT, which may contribute to our understanding
      of the mechanisms underlying stress-induced dysfunction of gap junctions.

PMID- 29223531
TI  - Self-assembly regulated anticancer activity of platinum coordinated
      selenomethionine.
AB  - It is urgently desired that self-assembly methods can be used to develop smart
      nanomedicines with adjustable anticancer activity and concise structure. Herein,
      we design carrier-free small molecule assemblies of platinum coordinated
      selenomethionine, which exhibit adjustable anticancer activity regulated by their
      self-assembly behaviors. The small molecule assemblies are prepared by
      coordination of selenomethionine esters with cisplatin. Their self-assembly
      behaviors can be tuned by esterification between selenomethionine and alcohols
      with different alkyl lengths, which results in adjustable anticancer activities.
      The coordination assemblies exhibit high anticancer activity as well as low side
      effects. Mechanistic studies indicate that they can consume glutathione (GSH) and
      therefore induce high level of reactive oxygen species (ROS) in cancer cells,
      which further lead to cell apoptosis. Our findings provide new strategies and
      insights in developing small molecule assemblies for cancer treatment.

PMID- 29223532
TI  - New insights into the influence of monofluorination on
      dimyristoylphosphatidylcholine membrane properties: A solid-state NMR study.

PMID- 29223533
TI  - Atomic structure and enzymatic insights into the vancomycin-resistant
      Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C.
AB  - The Enterococcus faecalis alkyl hydroperoxide reductase complex (AhpR) with its
      subunits AhpC (EfAhpC) and AhpF (EfAhpF) are of paramount importance to restore
      redox homeostasis. Recently, the novel phenomenon of swapping of the catalytic
      domains of EfAhpF was uncovered. Here, we visualized its counterpart EfAhpC (187
      residues) from the vancomycin-resistant E. faecalis (V583) bacterium by electron
      microscopy and demonstrate, that in contrast to other bacterial AhpCs, EfAhpC
      forms a stable decamer-ring irrespective of the redox state. The first
      crystallographic structure (2.8A resolution) of the C-terminal truncated form
      (EfAhpC1-172) confirms the decamer ring and provides new insight into a
      transition state in-between a fully folded to a locally unfolded conformation in
      the catalytic center due to redox modulation. Amino acid substitutions of
      residues in the N- and C-termini as well as the oligomeric interphase of EfAhpC
      provide information into their structural and enzymatic roles. Mutagenesis,
      enzymatic and biophysical studies reveal the effect of the unusual existence of
      four cysteines in EfAhpC, which might optimize the functional adaptation of the
      E. faecalis enzyme under various physiological conditions.

PMID- 29223534
TI  - Systemic recovery and therapeutic effects of transplanted allogenic and xenogenic
      mesenchymal stromal cells in a rat blunt chest trauma model.
AB  - BACKGROUND: Effective therapy of Acute Lung Injury (ALI) is still a major
      scientific and clinical problem. To define novel therapeutic strategies for
      sequelae of blunt chest trauma (TxT) like ALI/Acute Respiratory Distress
      Syndrome, we have investigated the immunomodulatory and regenerative effects of a
      single dose of ex vivo expanded human or rat mesenchymal stromal cells
      (hMSCs/rMSCs) with or without priming, immediately after the induction of TxT in
      Wistar rats. METHODS: We analyzed the histological score of lung injury, the cell
      count of the broncho alveolar lavage fluid (BAL), the change in local and
      systemic cytokine level and the recovery of the administered cells 24 h and 5
      days post trauma. RESULTS: The treatment with hMSCs reduced the injury score 24 h
      after trauma by at least 50% compared with TxT rats without MSCs. In general, TxT
      rats treated with hMSCs exhibited a lower level of pro-inflammatory cytokines
      (interleukin [IL]-1B, IL-6) and chemokines (C-X-C motif chemokine ligand 1
      [CXCL1], C-C motif chemokine ligand 2 [CCL2]), but a higher tumor necrosis factor
      alpha induced protein 6 (TNFAIP6) level in the BAL compared with TxT rats after
      24 h. Five days after trauma, cytokine levels and the distribution of
      inflammatory cells were similar to sham rats. In contrast, the treatment with
      rMSCs did not reveal such therapeutic effects on the injury score and cytokine
      levels, except for TNFAIP6 level. CONCLUSION: TxT represents a suitable model to
      study effects of MSCs as an acute treatment strategy after trauma. However, the
      source of MSCs has to be carefully considered in the design of future studies.

PMID- 29223535
TI  - Corrigendum to "A consensus introduction to serum replacements and serum-free
      media for cellular therapies" [Cytotherapy 19 (2017) 155-169].

PMID- 29223536
TI  - Polymeric gels for intravaginal drug delivery.
AB  - Intravaginal drug delivery can elicit a local effect, or deliver drugs
      systemically without hepatic first pass metabolism. There are a number of
      emerging areas in intravaginal drug delivery, but the vagina is a challenging
      route of administration, due to the clearance mechanisms present which result in
      poor retention of dosage forms, and the potential for irritation and other
      adverse reactions. Gel formulations are desirable due to the ease of application,
      spreading and that they cause little to no discomfort to the patient. However,
      these dosage forms, in particular, are poorly retained and traditional gels
      typically have little control over drug release rates. This has led to a large
      number of studies on improving the retention of vaginal gels and modulating the
      controlled release of drugs from the gel matrix. This review outlines the anatomy
      and physiology of the vagina, focussing on areas relevant to drug delivery.
      Medical applications of vaginally administered medicines is then discussed,
      followed by an overview of polymeric gels in intravaginal drug delivery. The
      sensorial properties of intravaginal gels, and how these relate to user
      compliance are also summarised. Finally, some important barriers to marketing
      approval are described.

PMID- 29223537
TI  - RANKL Signaling Sustains Primary Tumor Growth in Genetically Engineered Mouse
      Models of Lung Adenocarcinoma.
AB  - INTRODUCTION: NSCLC is the leading cause of cancer mortality. Recent
      retrospective clinical analyses suggest that blocking the receptor activator of
      NF-kappaB (RANK) signaling pathway inhibits the growth of NSCLC and might
      represent a new treatment strategy. METHODS: Receptor activator of NF-kappaB gene
      (RANK) and receptor activator of NF-kappaB ligand gene (RANKL) expression in
      human lung adenocarcinoma was interrogated from publicly available gene
      expression data sets. Several genetically engineered mouse models were used to
      evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth
      measured longitudinally using microcomputed tomography. A combination of RANKL
      blockade with cisplatin was tested to mirror an ongoing clinical trial. RESULTS:
      In human lung adenocarcinoma data sets, RANKL expression was associated with
      decreased survival and KRAS mutation, with the highest levels in tumors with co
      occurring KRAS and liver kinase B1 gene (LKB1) mutations. In KrasLSL-G12D/WT,
      KrasLSL-G12D/WT; Lkb1Flox/Flox and KrasLSL-G12D/WT; p53Flox/Flox mouse models of
      lung adenocarcinoma, we monitored an impaired progression of tumors upon RANKL
      blockade. Despite elevated expression of RANKL and RANK in immune cells,
      treatment response was not associated with major changes in the tumor immune
      microenvironment. Combined RANK-Fc with cisplatin revealed increased efficacy
      compared with that of single agents in p53- but not in Lkb1-deficient tumors.
      CONCLUSIONS: RANKL blocking agents impair the growth of primary lung tumors in
      several mouse models of lung adenocarcinoma and suggest that patients with KRAS
      mutant lung tumors will benefit from such treatments.

PMID- 29223538
TI  - Curcumin induces osteoblast differentiation through mild-endoplasmic reticulum
      stress-mediated such as BMP2 on osteoblast cells.
AB  - AIMS: Curcumin (diferuloylmethane or [1E,6E]-1,7-bis[4-hydroxy-3-methoxyphenyl]
      1,6heptadiene-3,5-dione) is a phenolic natural product derived from the rhizomes
      of the turmeric plant, Curcuma longa. It is reported to have various biological
      actions such as anti-oxidative, anti-inflammatory, and anti-cancer effects.
      However, the molecular mechanism of osteoblast differentiation by curcumin has
      not yet been reported. MAIN METHODS: The cytotoxicity of curcumin was identified
      using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. Expression of osteogenic markers and endoplasmic reticulum (ER) stress
      markers in C3H1-T1/2 cells were measured using reverse-transcriptase polymerase
      chain reaction (RT-PCR) and Western blotting. Alkaline phosphatase (ALP) staining
      was performed to assess ALP activity in C3H10T1/2 cells. Transcriptional activity
      was detected using a luciferase reporter assay. KEY FINDINGS: Curcumin increased
      the expression of genes such as distal-less homeobox 5 (Dlx5), runt-related
      transcription factor 2 (Runx2), ALP, and osteocalcin (OC), which subsequently
      induced osteoblast differentiation in C3H10T1/2 cells. In addition, ALP activity
      and mineralization was found to be increased by curcumin treatment. Curcumin also
      induced mild ER stress similar to bone morphogenetic protein 2 (BMP2) function in
      osteoblast cells. Next, we confirmed that curcumin increased mild ER stress and
      osteoblast differentiation similar to BMP2 in C3H10T1/2 mesenchymal stem cells.
      Transient transfection studies also showed that curcumin increased ATF6-Luc
      activity, while decreasing the activities of CREBH-Luc and SMILE-Luc. In
      addition, similar to BMP2, curcumin induced the phosphorylation of Smad 1/5/9.
      SIGNIFICANCE: Overall, these results demonstrate that curcumin-induced mild ER
      stress increases osteoblast differentiation via ATF6 expression in C3H10T1/2
      cells.

PMID- 29223539
TI  - Losartan suppresses the kainate-induced changes of angiotensin AT1 receptor
      expression in a model of comorbid hypertension and epilepsy.
AB  - AIMS: Experimental and clinical studies have demonstrated that components of
      renin-angiotensin system are elevated in the hippocampus in epileptogenic
      conditions. In the present work, we explored the changes in the expression of
      angiotensin II receptor, type 1 (AT1 receptor) in limbic structures, as well as
      the effect of the AT1 receptor antagonist losartan in a model of comorbid
      hypertension and epilepsy. MAIN METHODS: The expression of AT1 receptors was
      compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using
      immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE).
      The effect of losartan was studied on AT1 receptor expression in epileptic rats
      that were treated for a period of 4weeks after status epilepticus. KEY FINDINGS:
      The naive and epileptic SHRs were characterized by stronger protein expression of
      AT1 receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and
      the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were
      immunostained in the piriform cortex. Increased AT1 immunostaining was observed
      in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats.
      Losartan exerted stronger and structure-dependent suppression of AT1 receptor
      expression in SHRs compared to Wistar rats. SIGNIFICANCE: Our results confirm the
      important role of AT1 receptor in epilepsy and suggest that the AT1receptor
      antagonists could be used as a therapeutic strategy for treatment of comorbid
      hypertension and epilepsy.

PMID- 29223540
TI  - Protective effect of coptisine free base on indomethacin-induced gastric ulcers
      in rats: Characterization of potential molecular mechanisms.
AB  - AIMS: The aim of this study was to comparatively investigate the potential
      gastroprotective effect and underlying mechanisms of coptisine free base (CFB, 8
      hydroxy-7, 8-dihydrocoptisine), berberine and lansoprazole against indomethacin
      induced gastric ulcer in rats. MATERIALS AND METHODS: CFB (10, 20 and 40mg/kg),
      berberine (20mg/kg) and lansoprazole (30mg/kg) were orally administrated to rats
      prior to indometacin ingestion, and gastric lesions were evaluated
      macroscopically and histologically, and further analyzed by ELISA, qRT-PCR and
      Western blot. KEY FINDINGS: CFB exerted comparable or superior gastroprotective
      effect to berberine in protecting against indomethacin-induced gastric injury.
      CFB pretreatment significantly enhanced the levels of superoxide dismutase (SOD)
      and glutathione (GSH), and markedly decreased the malonaldehyde (MDA) content.
      CFB administration effectively suppressed the levels of myeloperoxidase (MPO),
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and
      angiotensin II (Ang II). Besides, CFB substantially up-regulated the mRNA
      expressions of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and
      promoted gastric mucosal prostaglandin E2 level (PGE2). Furthermore, CFB
      pretreatment remarkably increased the translocation of nuclear factor erythroid 2
      related factor 2 (Nrf2) from cytosol into the nucleus, and the expression of heme
      oxygenase-1 (HO-1), while significantly decreased the expression of mitogen
      activated protein Kinase Kinase 6 (MKK6) and translocation of p38 mitogen
      activated protein kinase (p38 MAPK). SIGNIFICANCE: This was the first
      investigation reporting the anti-ulcer effect of protoberberine alkaloid free
      base on in vivo rodent model. The gastroprotective mechanism of CFB might involve
      favorable regulation of antioxidant and anti-inflammatory status mediated, at
      least partially, by the Nrf2 signaling pathway and p38 MAPK translocation.

PMID- 29223541
TI  - Functional role of lncRNA LOC101927497 in N-methyl-N'-nitro-N-nitrosoguanidine
      induced malignantly transformed human gastric epithelial cells.
AB  - AIMS: Evidence shows that aberrant expression of long non-coding RNA (lncRNA) is
      closely associated with tumor development and progression. However, the role of
      lncRNA in environmental carcinogen induced gastric tumorigenesis remains largely
      unknown. This study aimed at investigating the function role of lncRNA in N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) induce malignantly transformed human
      gastric epithelial cells. MAIN METHODS: In this study, high-throughput sequencing
      and qRT-PCR assay revealed marked downregulation of lncRNA LOC101927497 in the
      malignant transformed gastric epithelial cells induced by MNNG (GES-1-T cells),
      gain-of-function and loss-of-function assays showed that LOC101927497 can
      suppress the proliferation and migration of GES-1-T cells in vitro. RNA antisense
      purification experiment showed that LOC101927497 interacted with miR-574-5p in
      GES-1-T cells the most obvious. Further studies suggested that LOC101927497 may
      function as a tumor suppressor by interacting with miR-574-5p. KEY FINDINGS:
      LncRNA LOC101927497 functions as a suppressor by interacting with miR-574-5p,
      thus inhibiting the malignant phenotype of GES-1-T cells. SIGNIFICANCE: To the
      best of our knowledge, this is the first study to demonstrate the role of lncRNA
      in MNNG-induced gastric tumorigenesis, and it will provide new insights into the
      role of lncRNA in environmental carcinogen-induced gastric cancer.

PMID- 29223542
TI  - Interval exercise training increases LIF expression and prevents myocardial
      infarction-induced skeletal muscle atrophy in rats.
AB  - AIMS: Myocardial infarction (MI) is commonly associated with body weight loss and
      skeletal muscle atrophy. Studies have shown that exercise training could give
      beneficial effects on skeletal muscle growth. Leukemia inhibitory factor (LIF) is
      a key regulator of muscle growth and regeneration. The aim of this study was to
      investigate the effects of interval exercise training (IET) on the expression of
      LIF and the MI-induced skeletal muscle atrophy. MAIN METHODS: Male Sprague-Dawley
      rats were used to establish the MI model by ligation of the left anterior
      descending coronary artery. Infarcted Rats were divided into two groups:
      sedentary MI group (MI) and MI with interval exercise group (ME), and compared to
      sham-operated group (Sham). Exercise-trained animals were subjected to eight
      weeks of IET. Cardiac function, collagen volume fraction, expression of LIF and
      its receptor LIFR, myofiber size, apoptosis and proliferation in gastrocnemius
      muscle were analyzed. KEY FINDINGS: IET increased heart functional performance
      and was accompanied with reversing cardiac pathological remodeling. Moreover, IET
      increased the expression of LIF and LIFR, activated signal transducer and
      activator of transcription (STAT3), reduced apoptosis and promoted proliferation
      in gastrocnemius muscle compared with the MI group. In addition, there was a
      significant negative correlation between skeletal muscle atrophy and LIF
      expression which was stimulated by IET in infarcted rats. SIGNIFICANCE: IET
      reverses MI-induced cardiac dysfunction and skeletal muscle atrophy. In addition,
      IET up-regulates the expression of muscle LIF/LIFR and activates the STAT3.

PMID- 29223543
TI  - Metagenomic sequencing of environmental DNA reveals marine faunal assemblages
      from the West Antarctic Peninsula.
AB  - The West Antarctic Peninsula (WAP) is the fastest warming region in Antarctica
      where climate impact on the cold-adapted marine ecosystem is already visible. To
      monitor faunal changes in remote vast bodies of Antarctic waters, efficient and
      informative tools are essential. High-throughput sequencing of environmental DNA
      (eDNA) has emerged as one such tool for monitoring biodiversity and ecosystems,
      as it increases detection sensitivity of taxa, and sampling is often simpler and
      less costly than traditional collection methods. We collected water samples from
      four WAP shallow (<=300m) shelf regions, recovered the eDNA therein, and
      performed metagenomic shotgun sequencing and analyses to determine the
      effectiveness of this method to assess marine benthic faunal diversity; this
      includes the detection of deep-water predatory king crabs whose potential
      shoreward expansion to warming shelves has sparked much concern. Using a
      customized bioinformatics pipeline, we identified abundant signatures of common
      benthic invertebrate fauna, endemic notothenioid fishes, as well as lithodid king
      crabs. We also uncovered species richness and diversity comparable to biological
      inventories compiled by the use of traditional survey methods, supporting the
      efficacy of the eDNA shotgun sequencing approach. As the rate of eDNA degradation
      affects faunal detection sensitivity, we also quantified mitochondrial ND2 gene
      copies in eDNA derived from a WAP icefish and found ND2 copies persisted to at
      least 20days in the cold WAP water, much longer than values reported for
      temperate environments. We propose that eDNA metagenomic sequencing complements
      traditional sampling, and combining both will enable more inclusive biodiversity
      detection and faunal change monitoring in the vast Southern Ocean.

PMID- 29223544
TI  - Does clinic visit education within a multidisciplinary center improve health
      literacy scores in caregivers of children with complex colorectal conditions?
AB  - INTRODUCTION: Health literacy is low in an estimated one-third of the US
      population. Little is known about the health literacy of caregivers of children
      with colorectal conditions. The objective of this study was to investigate
      whether a timed health literacy intervention could improve health literacy in
      this population. METHODS: We used the BRIEF Health Literacy screening (BHLS) tool
      on caregivers of children who came to our colorectal clinic. Health literacy was
      categorized as inadequate, marginal, or adequate. The number of caregivers with
      adequate health literacy was compared to the number of clinic visits and
      socioeconomic status. RESULTS: We included 233 caregivers. The average number of
      clinic visits was 3.5 over 1.2years. At the first clinic visit, 70% (n=98) of
      caregivers had "adequate" health literacy. Scores improved to 88% (p=0.024) after
      the fourth visit. Socioeconomic factors were not associated with health literacy.
      Patients of caregivers with "adequate" health literacy visited our clinic 3.8
      times, compared to 2.7 times for those with lower literacy (p=0.006). CONCLUSION:
      Emphasis on providing an education-based approach at each visit increased health
      literacy significantly. As expected, health literacy was lowest during the first
      visit, which we believe is the optimal time to implement educational
      interventions. TYPE OF STUDY: Case Control/Retrospective Comparative Study. LEVEL
      OF EVIDENCE: Level III.

PMID- 29223545
TI  - The bowel function and quality of life of Hirschsprung disease patients who have
      reached 18 years of age or older - the long-term outcomes after undergoing the
      transabdominal soave procedure.
AB  - BACKGROUND/PURPOSE: Hirschsprung disease (HD) is considered curable, but the
      postoperative bowel function is not always satisfactory. In this study, we
      evaluated the general condition, bowel function, and social performance in adults
      who were older than 17years of age who had undergone definitive operations in
      childhood. METHOD: From 1984 to 2016, 110 patients with HD underwent definitive
      surgery at our institute. Sixty-three patients who had undergone the
      transabdominal Soave procedure reached 18years of age. Their present status and
      symptoms, anorectal function, genitourinary function, and social performance were
      evaluated during the clinical follow-up via a questionnaire survey. RESULT: The
      mean age of the questionnaire respondents was 25.0 (19-37) years. The bowel
      function was mostly good. However, 56% of patients had abdominal pain more than
      once a week. Regarding evacuation symptoms, incontinence and soiling occurred in
      18.7%. Among the respondents 33.3% were married, and 60% of those who were
      married had children. The respondents had achieved success in their education and
      professional careers. CONCLUSION: The bowel function of most patients was
      satisfactory, although some had chronic abdominal symptoms. Pediatric surgeons
      should continue trying to achieve complete bowel function after definitive
      surgery of HD. TYPE OF STUDY: Prospective Cohort Study. LEVEL OF EVIDENCE: Level
      III.

PMID- 29223546
TI  - Sigmoidocolocystoplasty for neurogenic bladder reviewed after 20 years.
AB  - BACKGROUND/PURPOSE: We report the current status of patients who underwent
      augmentation cystoplasty (AC) at least 20years previously. METHODS: Surgical
      history, incidence of urinary tract infection (UTI) and bladder stones,
      vesicoureteral reflux (VUR), urine cytology, renal function, a colon cancer tumor
      marker (carcinoembryonic antigen: CEA), and patient outcomes were assessed.
      RESULTS: Forty patients who underwent AC (mean age: 34.4years; mean follow-up
      time: 24.3years) were analyzed. Mean age at AC was 11years. Incidence of bladder
      stones was 30%. There were no incidences of carcinoma after AC, and CEA levels
      were not increased. Ureteral reimplantation (URI) was performed in 21 patients.
      URI performed at the same time as AC was successful in 14 cases (93%) and
      unsuccessful in 1 (7%) because of persistent VUR. UTI developed after AC in only
      1 patient (2.5%) with persistent VUR. This patient required unilateral
      nephrectomy 18years after the AC because of repeated UTIs. Thirty-four patients
      (85%) were employed, and 4 (10%) were married. Two of the 19 female patients
      (11%) had experienced pregnancy and delivery. Five patients (13%) had mental
      disorders. CONCLUSION: Ultra long-term follow-up suggests that AC is a safe
      procedure with manageable sequelae, although some mental health issues remain.
      TYPE OF STUDY: Case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

PMID- 29223548
TI  - Co-occurrence of early gut colonization in neonatal piglets with microbiota in
      the maternal and surrounding delivery environments.
AB  - The early development of gut microbiota plays a fundamental role in host health;
      so far, the main origins of the first colonization in newborn piglets are largely
      unclear. This study aimed to investigate the early development of gut microbiota
      in newborn piglets during lactation and their co-occurrence with microbes in the
      maternal and surrounding environments by Illumina MiSeq sequencing of 16S
      ribosomal RNA genes. The results showed that the microbial richness and diversity
      in piglets' feces (PF) significantly increased from birth to weaning (21 d). The
      composition and function of microbiota in the feces of piglets after birth tended
      to be similar to those from the slatted floor (FL), sow's milk (SM) and nipple
      surface (SN), and lacter, the fecal microbial communities of piglets later during
      lactation were more similar to their mother's. SourceTracker analysis showed that
      the microbiota from the FL, SM and SN were most likely the earliest passengers to
      the neonatal gastrointestinal tract, but did not have a long stay during
      lactation. The sow's fecal microbiota were easier to colonize in newborn piglet's
      guts via the co-occurrence effect with former settlers. This study suggests that
      microbes from the maternal and surrounding environments may play an important
      role in the microbial succession of newborn piglets after birth.

PMID- 29223549
TI  - The Relation between Blood Count Parameters and Stroke in Patients with
      Intermediate Carotid Artery Stenosis.

PMID- 29223550
TI  - Comparative Risks of Ischemic Stroke in Atrial Flutter versus Atrial
      Fibrillation.
AB  - INTRODUCTION: The aim of this study was to compare the risk of ischemic stroke in
      patients who have atrial fibrillation and patients who have atrial flutter.
      METHODS: Using inpatient and outpatient Medicare claims data from 2008 to 2014
      for a 5% sample of all beneficiaries 66 years of age or older, we identified
      patients diagnosed with atrial fibrillation and those diagnosed with atrial
      flutter. The primary outcome was ischemic stroke. In the primary analysis,
      patients with atrial flutter were censored upon converting to fibrillation; in a
      secondary analysis, they were not. Survival statistics were used to compare
      incidence of stroke in patients with flutter and patients with fibrillation. Cox
      proportional hazards analysis was used to compare the associations of flutter and
      fibrillation with ischemic stroke after adjustment for demographics and risk
      factors. RESULTS: We identified 14,953 patients with flutter and 318,138 with
      fibrillation. During a mean follow-up period of 2.8 (+/-2.3) years, we identified
      18,900 ischemic strokes. The annual incidence of ischemic stroke in patients with
      flutter was 1.38% (95% confidence interval [CI] 1.22%-1.57%) compared with 2.02%
      (95% CI 1.99%-2.05%) in patients with fibrillation. After adjustment for
      demographics and stroke risk factors, flutter was associated with a lower risk of
      stroke compared with fibrillation (hazard ratio .69; 95% CI .60-.79, P < .05).
      Within 1 year, 65.7% (95% CI 64.9%-66.4%) of patients with flutter converted to
      fibrillation but remained at a lower risk of ischemic stroke (hazard ratio .85;
      95% CI .78-.92). CONCLUSIONS: Patients with atrial flutter faced a lower risk of
      ischemic stroke than patients with atrial fibrillation.

PMID- 29223551
TI  - Recent advances in delivery of antifungal agents for therapeutic management of
      candidiasis.
AB  - Candidiasis is a fungal infection caused by yeasts that belong to the genus
      Candida. There are over twenty species of Candida yeasts that can cause infection
      in humans, the most common of which is Candida albicans. Candida yeasts normally
      reside in the intestinal tract and can be found on mucous membranes and skin
      without causing infection; however, overgrowth of these organisms can cause
      symptoms to develop. Presence of other diseases that compromises the patient's
      immunity makes it more difficult to treat. Candidiasis is majorly divided into
      superficial infections (oral or vaginal) and systemic infections, also known as
      invasive candidiasis. The conventional therapeutic modalities used to treat
      candidiasis are associated with several side effects that limits the dose and
      dosing frequency. Development of novel drug delivery systems for reduction in
      dose and alleviation of side effects is an important strategy to improve the
      clinical efficacy and patient acceptability. This review gives a bird's eye view
      of the classification and current therapeutic regime of candidiasis. It presents
      the varied types of drug delivery systems that have been exploited for delivery
      of antifungal agents with measurable benefits. It also touches upon echinocandins
      a relatively new class of drugs that are amenable for translation into novel
      dosage forms with application against biofilm producing and fluconazole resistant
      strains contributing to a better therapeutic management of candidiasis.

PMID- 29223552
TI  - Caffeine - rich infusion from Cola nitida (kola nut) inhibits major carbohydrate
      catabolic enzymes; abates redox imbalance; and modulates oxidative dysregulated
      metabolic pathways and metabolites in Fe2+-induced hepatic toxicity.
AB  - The antioxidative and antidiabetic effects and toxicity of caffeine-rich infusion
      of Cola nitida were investigated using in vitro, ex vivo and in silico models. C.
      nitida was infused in boiling water and allowed to cool before concentrating at
      <50 degrees C. HPLC analysis of the infusion revealed a caffeine content of
      80.08%. The infusion showed potent in vitro antioxidant activity by significantly
      (p<0.05) scavenging 2,2'-diphenyl-1-picrylhydrazyl (DPPH). It significantly
      (p<0.05) inhibited alpha-glucosidase and alpha-amylase activities. Treatment of
      Fe2+ induced oxidative hepatic tissues with the infusion led to increase
      Superoxide Dismutase (SOD) and catalase activities, and glutathione (GSH) level
      as well as decreased malondialdehyde (MDA) level. FTIR spectroscopy of hepatic
      metabolite revealed restoration of oxidative-induced depleted functional groups
      by the infusion. LC-MS analysis of the metabolite also revealed restoration of
      most depleted metabolites with concomitant generation of 4-O-Methylgallic, (-)
      Epicatechin sulfate, L-Arginine, L-tyrosine, Citric acid and Decanoic acid in
      infusion-treated tissues. Pathway analysis of the identified metabolites revealed
      the presence of 21 metabolic pathways involved in normal hepatic tissues, 12 in
      oxidative injured tissues and 17 in the treated tissues. Treatment with the
      infusion restored 4 metabolic pathways common to the normal tissue and further
      activated 4 additional pathways. Prediction of oral toxicity of caffeine showed
      it to belong to class 3, with a LD50 of 127mg/kg. Its toxicity target was
      predicted as Adenosine Receptor A2a. It was also predicted to be an inhibitor of
      CYP1A2. These results suggest the antioxidative and antidiabetic properties of C.
      nitida infusion, with caffeine as the major constituent.

PMID- 29223553
TI  - Lipopolysaccharide induces autophagy by targeting the AMPK-mTOR pathway in Human
      Nasal Epithelial Cells.
AB  - Chronic rhinosinusitis (CRS) is a well-known disease encountered in the
      department of otorhinolaryngology, yet little is known about its pathogenesis.
      Autophagy, a lysosome-dependent degradation process, has been reported to be
      involved in the process of many chronic inflammatory diseases. Here we tried to
      evaluate the function of autophagy in CRS as well as explore the related
      mechanisms. We first stained light chain 3B (LC3B) with immunohistochemistry in
      uncinate tissues (UT) from patients with and without CRS and found that its
      expression was up-regulated in CRS patients. Then, Human Nasal Epithelial Cells
      (HNEpC) were treated with lipopolysaccharide (LPS), one of the most common
      pathogenic elements in CRS, and we found that autophagy was induced in a dose-
      and time-dependent manner. This is supported by a rise in the expression of light
      chain 3B-II (LC3B-II), accumulation of GFP-LC3 vesicles, as well as decreased p62
      expression. Furthermore, we found that LPS promoted AMPK phosphorylation and
      inactived mTOR, while AMPK inhibition by compound C significantly attenuated LPS
      induced autophagy. Besides, treatment of HNEpC with LPS increased the amount of
      Toll-like receptor 4 (TLR4) while inhibiting TLR4 by Polymyxin B (PMB) declined
      autophagy caused by LPS. Taken together, our study first demonstrated that LPS
      caused autophagy in HNEpC, and this process was AMPK-mTOR dependent. These data
      suggested the relationship between LPS and autophagy in the pathogenesis of CRS.

PMID- 29223554
TI  - Oral administration of Nigella sativa oil and thymoquinone attenuates long term
      cisplatin treatment induced toxicity and oxidative damage in rat kidney.
AB  - Cisplatin (CP) is an effective anti-cancer drug which causes remarkable toxicity
      to the kidney, particularly to proximal tubules, by generating reactive oxygen
      species. Nigella sativa (NS), commonly known as "black cumin" reduces the
      progression of various kidney disorders. Thymoquinone (TQ), the major bioactive
      constituent of NS seeds, has been credited for various pharmacological effects of
      NS. Since, a typical clinical CP dosing regimen involves CP administration in
      multiple cycles over a long time duration, hence the present study aimed to
      evaluate the renoprotective efficacy of NS oil and TQ against multiple dose CP
      treatment induced deleterious biochemical and histological alterations in rat
      kidney. Adult male Wistar rats were divided into six groups viz. control, CP,
      CPNSO, CPTQ, NSO and TQ. Animals in CPNSO and CPTQ groups were pre-administered
      NSO (2ml/kg bwt, orally) and TQ (1.5mg/kg bwt, orally) respectively for 14 days
      and were then treated with CP (3mg/kg bwt, i.p), every fourth day for 20 days
      while still receiving NSO/TQ. NSO and TQ administration, prior to and along with
      CP treatment, attenuated CP induced renal functional impairment as evident by
      significantly restored serum creatinine and blood urea nitrogen levels. CP
      treatment alone led to significant decline in the specific activities of brush
      border membrane (BBM) marker enzymes viz. ALP (-46.64%), GGTase (-50.24%) and LAP
      (-42.15%), while NSO or TQ administration to CP treated rats significantly
      prevented the decline in the activities of these enzymes in isolated BBM vesicles
      (BBMVs) as well as in the homogenates of renal cortex and medulla. Furthermore,
      both NSO and TQ administration also mitigated the CP induced perturbations in
      renal metabolic and redox status. Histological studies supported these
      biochemical results showing significant attenuation of CP induced kidney damage
      in CPNSO and CPTQ cotreated groups. Thus, NSO and TQ have excellent scope for use
      as functional food or combinatorial nutraceuticals in CP chemotherapy to
      ameliorate the accompanying nephropathy in long term cancer chemotherapy.

PMID- 29223555
TI  - Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and
      metastasis of lung cancer.
AB  - Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous
      RNAs, can regulate gene expression in mammals. CircRNAs have recently been
      identified as microRNA sponges and involved in the development of some human
      diseases. However, the role of circRNAs in the process of tumorigenesis and
      development of lung cancer remains vague. The purpose of this study is to
      investigate the role of circRNAs in the lung cancer. In this study, we chose
      hsa_circ_0000064 as a targeted circRNA to investigate its clinical significances
      in lung cancer patients. The result indicated that hsa_circ_0000064 was up
      regulated in lung cancer tissues and lung cancer cell lines (A549 and H1229).
      Moreover, its aberrant expression was correlated with several clinical
      characteristics, including T stage, lymphatic metastasis, and TNM stage.
      Fluorescence in situ hybridization detected that hsa_circ_0000064 was mostly
      located in the cytoplasm in A549 and H1229 cells. In addition, knockdown of
      hsa_circ_0000064 with siRNA dramatically attenuated the proliferation, blocked
      cell cycle progression, and promoted cell apoptosis. Western blot analysis showed
      that the protein levels of caspase-3, caspase-9, bax, p21, CDK6 and cyclin D1
      significantly restrained by si-hsa_circ_0000064, while the expression of bcl-2
      notably increased in A549 and H1229 cells. Further, si-hsa_circ_0000064 also
      abated migration and invasion activities of A549 and H1229 cells, which may be
      associated with reduced expressions of MMP-2 and MMP-9. In general, our data
      suggest that hsa_circ_0000064 represents a novel potential biomarker and
      therapeutic target of lung cancer.

PMID- 29223556
TI  - Therapeutic effects of thymoquinone for the treatment of central nervous system
      tumors: A review.
AB  - BACKGROUND: The aim of this study is to review the effects of thymoquinone (TQ)
      against central nervous systems (CNS) tumors. METHODS: In this study, we
      extensively reviewed all articles on the terms of N. sativa, TQ, CNS tumors, and
      different disorders in PubMed, Science Direct, Scopus, and Google Scholar
      databases between the years 1990 and 2017. RESULTS: The present study found that
      TQ has many therapeutic effects due to its antioxidant, anti-inflammatory, and
      anti-proliferative activities. Experimental studies indicated the protective
      effects of TQ against CNS tumors. The anti-tumor effects of TQ are mainly caused
      by inducing G2/M cell cycle arrest, apoptotic pathways, inhibiting autophagy,
      angiogenesis, invasion, and migration and also by enhancing the efficacy of
      chemotherapeutic drugs. Although, the study observed no significant toxicity of
      TQ in the experimental models, more clinical studies are needed to confirm the
      safety and efficacy of TQ for human. CONCLUSIONS: The present review found that
      TQ treatment can be considered as a promising therapeutic strategy for human
      malignant CNS in future.

PMID- 29223557
TI  - Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with
      Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin-OMAcor iN residual
      hyperTrIglyCeridemia), a Randomized, Double-blind, and Placebo-controlled Trial.
AB  - PURPOSE: The purpose of this study was to examine the efficacy and safety of
      adding omega-3 fatty acids to rosuvastatin in patients with residual
      hypertriglyceridemia despite statin treatment. METHODS: This study was a
      multicenter, randomized, double-blind, placebo-controlled study. After a 4-week
      run-in period of rosuvastatin treatment, the patients who had residual
      hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus omega-3
      fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group)
      with a 1:1 ratio and were prescribed each medication for 8 weeks. FINDINGS: A
      total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7%
      male). After 8 weeks of treatment, the percentage change from baseline in
      triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group
      than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: 
      10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering
      effect of omega-3 fatty acids was greater when baseline TG or non-HDL-C levels
      were high and body mass index was low. The incidence of adverse events was not
      significantly different between the 2 groups. IMPLICATIONS: In patients with
      residual hypertriglyceridemia despite statin treatment, a combination of omega-3
      fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C
      than rosuvastatin alone. Further study is needed to determine whether the
      advantages of this lipid profile of omega-3 fatty acids actually leads to the
      prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

PMID- 29223559
TI  - Assessment of the stability of sheep sausages with the addition of different
      concentrations of Origanum vulgare extract during storage.
AB  - The aim of this study was to assess the stability of sheep sausages with the
      addition of different concentrations of Origanum vulgare extract during storage.
      Five treatments were prepared: without natural antioxidant (control), sodium
      erythorbate 500mg/kg (ER), and three amounts of extract (N1=4964.51mg/kg,
      N2=6630.98mg/kg and N3=8038.20mg/kg). From appearance sensory analysis, control
      treatment differed significantly compared to ER (P<0.05) and N3 (P<0.01) groups,
      with intense red color, agreeing with trend of a* values. On the other hand,
      oregano extract improved the lipid and protein stability of cooked sausages
      during the storage time. Regarding volatile compounds from lipid oxidation, the
      N2 group presented the lowest values at the end of chilled period. In conclusion,
      the oregano extract showed antioxidant potential equivalent to sodium erythorbate
      at intermediate and high levels, calculated by DPPH? and FRAP methods, and most
      of the parameters were not compromised, allowing synthetic antioxidants replaced
      while maintaining the nutritional and sensory quality of cooked sausages.

PMID- 29223558
TI  - Consumer acceptance of minced meat patties from boars in four European countries.
AB  - A consumer study was performed in four EU countries to further clarify the
      acceptability of meat with boar taint. In Denmark, France, Italy and Poland, a
      total of 476 female consumers evaluated 8 meat patties from boars with varying
      levels of skatole (0.10-0.40MUg/g fat tissue) and androstenone (0.47-2.00 MUg/g
      fat tissue), in a pair-wise comparison with patties from castrates. Boar meat
      patties were always less preferred than the castrate meat patties, regardless of
      the level of androstenone and skatole. Acceptability of the boar meat patties
      decreased with increasing skatole level. In samples with low skatole levels,
      higher levels of androstenone also reduced acceptability among androstenone
      sensitive consumers. No clear threshold levels for androstenone and skatole could
      be identified. Maps presenting the reduction in preference due to increasing
      levels of skatole and androstenone, and corrected for the general acceptance of
      the meat product were developed, taking into account androstenone sensitivity.
      Further work is needed, covering the whole range of androstenone and skatole
      levels found in entire male pigs and for a wider set of meat products.

PMID- 29223560
TI  - The relationship between intestinal and oral mucosa microcirculation in
      anaesthetized horses.
AB  - OBJECTIVE: To compare alteration in intestinal blood flow in anaesthetized horses
      with changes in oral mucosa blood flow. STUDY DESIGN: Prospective, randomized
      clinical study. ANIMALS: Eight warmblood horses. METHODS: After induction with
      guaifenesin and ketamine, anaesthesia was maintained with isoflurane at 1.5 vol%
      in oxygen. The tissue blood flow was measured using laser Doppler flowmetry at
      the jejunum, colon, rectal mucosa, oesophageal mucosa and the oral mucosa. After
      three baseline measurements, blood flow was first increased by dobutamine
      infusion and thereafter decreased by increasing isoflurane concentration and all
      measurements repeated twice. anova was used for comparing the measured parameters
      to baseline and correlation between the different measurement localizations was
      examined using Pearson correlation (p < 0.05). RESULTS: Microperfusion at all
      measurement sites increased significantly during dobutamine infusion and
      decreased significantly during high isoflurane concentration. There was a
      significant correlation between flow at the oral mucosa and flow at the jejunum
      (r2 = 0.77, p = 0.002), colon (r2 = 0.76, p < 0.001), rectal mucosa (r2 = 0.88, p
      < 0.001) and oesophageal mucosa (r2 = 0.83, p <0.001). CONCLUSIONS AND CLINICAL
      RELEVANCE: Oral mucosa blood flow can be used in isoflurane anaesthetized horses
      to reflect changes of intestinal microcirculation.

PMID- 29223561
TI  - Microglia and astrocyte activation in the spinal cord of lame horses.
AB  - OBJECTIVE: To determine the microglial and astrocyte response to painful lameness
      in horses. STUDY DESIGN: Ionized calcium binding adaptor molecule 1 (Iba-1) and
      glial fibrillary acidic protein (GFAP) expression, cell density and morphology
      were determined through immunofluorescence within the dorsal horn of equine
      spinal cord. ANIMALS: A total of five adult horses with acute or chronic
      unilateral lameness, previously scheduled for euthanasia. METHODS:
      Musculoskeletal lameness was evaluated in five horses through visual evaluation
      according to clinical guidelines. Spinal cord samples were obtained immediately
      after euthanasia, and distal limb lesions were confirmed through dissection and
      radiography. Iba-1 immunostaining was used for detection and characterization of
      dorsal horn microglia. GFAP was used for immunostaining of dorsal horn
      astrocytes. Iba-1 and GFAP labeled cells were quantified in the dorsal horn, and
      intensity of fluorescence was compared between the ipsi- and contralateral dorsal
      horn to the affected limb, and between dorsal horn segments of all horses.
      RESULTS: Iba-1 expression was higher in the ipsilateral dorsal horn of the
      affected limb in contrast to the contralateral side dorsal horn. GFAP markers did
      not demonstrate increased astrocytic activity on the dorsal horn ipsilateral side
      to the distal limb lesion of affected horses. Horses with acute lameness
      predominantly had a spherical shape microglial phenotype, while cells from
      chronic lameness cases had variable morphology. Astrocytes evidenced small somas
      and large processes in both acute and chronic lameness, with higher GFAP
      localization in the main branches. As in the case of rodents, the localization of
      microglia and astrocytes in horses was mainly situated within laminae I, II and
      III. CONCLUSIONS AND CLINICAL RELEVANCE: Iba-1 and GFAP are functional and
      morphological markers of spinal microglial cells and astrocytes in horses with
      lameness.

PMID- 29223562
TI  - Can Adolescent Drivers' Motor Vehicle Crash Risk Be Reduced by Pre-Licensure
      Intervention?
AB  - PURPOSE: Although motor vehicle crashes are the leading cause of death for
      adolescents, there is a scarcity of research addressing adolescents' lack of pre
      licensure practical driving experience, which is theorized to increase their post
      licensure crash risk. METHODS: Utilizing police-reported crashes and survey data
      from a randomized and quasi-randomized trial (n = 458 adolescents, 16 or 17 years
      of age at enrollment), the impact of a parent-directed supervised practice
      driving intervention and a comprehensive on-road driving assessment (ODA) with
      feedback was evaluated on adolescent drivers' motor vehicle crashes involvement.
      RESULTS: Compared with the control condition, a nonsignificant 20% relative
      reduction in risk was observed for the parent-directed intervention: adjusted
      hazard ratio  = .80 (95% confidence interval [CI] .44, 1.43); the unadjusted
      absolute risk reduction was 1.1% (95% CI -4.4, 7.1). Exposure to the ODA resulted
      in an 53% relative reduction of risk: adjusted hazard ratio  = .47 (95% CI .24,
      .91); the unadjusted absolute risk reduction was 5.4% (95% CI -.3, 10.7).
      CONCLUSIONS: Comprehensive ODA might be protective for adolescents; however,
      additional research is needed.

PMID- 29223563
TI  - Sexual Identity, Adverse Childhood Experiences, and Suicidal Behaviors.
AB  - PURPOSE: The objective of this study was to examine the influence of sexual
      identity and adverse childhood experiences (ACEs) on suicidal behaviors in a
      population-based sample of high school students. METHODS: A two-stage cluster
      random sampling design was used to recruit 5,108 students from 97 high schools. A
      total of 4,955 students (97%) provided information that allowed for
      classification of sexual identity into three groups: (1) lesbian, gay, or
      bisexual (LGB) (10%); (2) not sure (4.6%); and (3) heterosexual (85.4%). Five
      measures of childhood abuse and household dysfunction were summed, and the ACE
      score was categorized as 0, 1, 2, and 3-5 ACEs. Weighted logistic regression was
      used to assess the influence of sexual identity, ACEs, and their interaction on
      suicide ideation and attempts in the past 12 months. RESULTS: Compared with
      heterosexual students, those who were LGB and were not sure had higher odds of
      suicide ideation and attempts. There was also a graded relationship between
      cumulative ACE exposure and suicidal behaviors. Although sexual identity/ACE
      interaction was not observed, LGB/not sure students who experienced a high number
      of ACEs were disproportionately affected. Compared with heterosexual students
      with 0 ACE, LGB/not sure students with 0 ACE (adjusted odds ratio [AOR] = 3.32,
      95% confidence interval [CI] = 1.96-5.61), 1 ACE (AOR = 6.58, 95% CI = 4.05
      10.71), 2 ACEs (AOR 13.50, 95% CI = 8.45-21.58), and 3-5 ACEs (AOR = 14.04, 95%
      CI = 8.72, 22.62) had higher odds of suicide ideation. A similar pattern was
      observed for suicide attempts. CONCLUSIONS: LGB and students not sure of their
      sexual identity with greater exposure to ACEs have disproportionately high levels
      of suicide ideation and attempts. Trauma-informed interventions for these
      populations are warranted.

PMID- 29223564
TI  - Indocyanine green-assisted parametrial dissection during type C1 radical
      hysterectomy after sentinel lymph node biopsy in early stage cervical cancer.
AB  - OBJECTIVES: The standard treatment for FIGO stage 1B1 cervical cancer is radical
      hysterectomy (RH) [1]. Indocyanine-green (ICG) is a drug injected within the
      cervical stroma to detect the sentinel lymph node (SLN) in cervical cancer [2,3].
      ICG travels through the lymphatic channels in the lateral parametrium, which
      results enhanced with green, before reaching the SLNs. This could help
      identifying the surgical landmarks. The aim of this video is to propose a new
      approach to perform parametrial dissection as part of RH under the guidance of
      ICG. METHODS: The patient was a 49-years old woman diagnosed with a FIGO 1B1
      moderately-differentiated cervical squamous cell carcinoma. No evidence of
      lymphoadenopathy on pre-operative imaging. 0.25ml of ICG (1.25mg/ml) were
      injected superficially and deep at 3 and 9 o'clock in the cervix as first step of
      the operation. Bilateral SLN biopsy followed by type C1 RH with bilateral
      salpingo-oophorectomy and bilateral pelvic node dissection was performed. Near
      infrared camera (PINPOINT(r) - Novadaq Technologies) was used during parametrial
      dissection. RESULTS: ICG was used as a guide to demarcate the parametrial tissue
      and assist the dissection of the lateral (paracervix) and anterior (vesico
      uterine ligament) parametrium off the surrounding structures (bladder and
      ureter). Operation time was 150min and intraoperative estimated blood loss was 50
      mls. No intraoperative or postoperative complication was reported. CONCLUSIONS:
      ICG-assisted parametrial dissection during RH after SLN biopsy in early stage
      cervical cancer can be a useful tool to guide the surgeon to perform the
      procedure and potentially improve surgical outcomes.

PMID- 29223565
TI  - Compressively sampled MR image reconstruction using generalized thresholding
      iterative algorithm.
AB  - Compressed sensing (CS) is an emerging area of interest in Magnetic Resonance
      Imaging (MRI). CS is used for the reconstruction of the images from a very
      limited number of samples in k-space. This significantly reduces the MRI data
      acquisition time. One important requirement for signal recovery in CS is the use
      of an appropriate non-linear reconstruction algorithm. It is a challenging task
      to choose a reconstruction algorithm that would accurately reconstruct the MR
      images from the under-sampled k-space data. Various algorithms have been used to
      solve the system of non-linear equations for better image quality and
      reconstruction speed in CS. In the recent past, iterative soft thresholding
      algorithm (ISTA) has been introduced in CS-MRI. This algorithm directly cancels
      the incoherent artifacts produced because of the undersampling in k-space. This
      paper introduces an improved iterative algorithm based on p-thresholding
      technique for CS-MRI image reconstruction. The use of p-thresholding function
      promotes sparsity in the image which is a key factor for CS based image
      reconstruction. The p-thresholding based iterative algorithm is a modification of
      ISTA, and minimizes non-convex functions. It has been shown that the proposed p
      thresholding iterative algorithm can be used effectively to recover fully sampled
      image from the under-sampled data in MRI. The performance of the proposed method
      is verified using simulated and actual MRI data taken at St. Mary's Hospital,
      London. The quality of the reconstructed images is measured in terms of peak
      signal-to-noise ratio (PSNR), artifact power (AP), and structural similarity
      index measure (SSIM). The proposed approach shows improved performance when
      compared to other iterative algorithms based on log thresholding, soft
      thresholding and hard thresholding techniques at different reduction factors.

PMID- 29223566
TI  - Progress in proton-detected solid-state NMR (SSNMR): Super-fast 2D SSNMR
      collection for nano-mole-scale proteins.
AB  - Proton-detected solid-state NMR (SSNMR) spectroscopy has attracted much attention
      due to its excellent sensitivity and effectiveness in the analysis of trace
      amounts of amyloid proteins and other important biological systems. In this
      perspective article, we present the recent sensitivity limit of 1H-detected SSNMR
      using "ultra-fast" magic-angle spinning (MAS) at a spinning rate (nuR) of 80-100
      kHz. It was demonstrated that the high sensitivity of 1H-detected SSNMR at nuR of
      100 kHz and fast recycling using the paramagnetic-assisted condensed data
      collection (PACC) approach permitted "super-fast" collection of 1H-detected 2D
      protein SSNMR. A 1H-detected 2D 1H-15N correlation SSNMR spectrum for ~27 nmol of
      a uniformly 13C- and 15N-labeled GB1 protein sample in microcrystalline form was
      acquired in only 9 s with 50% non-uniform sampling and short recycle delays of
      100 ms. Additional data suggests that it is now feasible to detect as little as 1
      nmol of the protein in 5.9 h by 1H-detected 2D 1H-15N SSNMR at a nominal signal
      to-noise ratio of five. The demonstrated sensitivity is comparable to that of
      modern solution protein NMR. Moreover, this article summarizes the influence of
      ultra-fast MAS and 1H-detection on the spectral resolution and sensitivity of
      protein SSNMR. Recent progress in signal assignment and structural elucidation by
      1H-detected protein SSNMR is outlined with both theoretical and experimental
      aspects.

PMID- 29223567
TI  - Predictive ability of the EVARUCI scale and COMHON index for pressure injury risk
      in critically ill patients: A diagnostic accuracy study.
AB  - BACKGROUND: Hospital-acquired pressure injuries are a costly and largely
      preventable complication occurring in a variety of acute care settings. Patients
      admitted to the intensive care unit are at greater risk of developing pressure
      injuries. OBJECTIVE: To determine whether the efficiency of scales to measure
      pressure injury risk increase when a continuously updated 3-day moving average
      method is used. METHODS: With a retrospective cohort design we recruited 3085
      patients treated between June 2011 and February 2015 in the intensive care unit
      of a tertiary level university hospital. The present study included 2777 patients
      admitted to the Intensive Care Unit of the Hospital Universitario de Canarias,
      Spain. Patients were evaluated daily with two scales to measure pressure injury
      risk: the Current Risk Assessment Scale for Pressure injury in Intensive Care
      scale (EVARUCI scale) and the Conscious level-Mobility-Haemodynamics-Oxygenation
      Nutrition Index (COMHON). The moving average was used to create a series of three
      day averages from the complete time-data set. The moving average method was used
      to analyze data points by creating series of averages of three days subsets of
      the time-data set. We calculated the efficiency of the method as the product of
      positive (PPV) and negative predicted values (NPV) for each scale. RESULTS: The
      efficiency using the moving average method was: PPV x NPV=0.483*0.907=0.438
      (standard deviation=0.059), for EVARUCI Scale, and. PPV x NPV=0.552*0.806=0.445
      (standard deviation=0.075) for COMHON Index. CONCLUSIONS: The efficiency using
      the moving average method was higher, than the efficiency of other methods
      previously reported (0.360+/-0.009 on average). The present study provides a
      useful procedure for nurses in clinical practice to assess whether a particular
      patient is protected against the appearance of pressure injury. The instrument
      should be used focusing on negative predictive value to indicate protection
      against pressure injury.

PMID- 29223568
TI  - N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, affects
      cellular content of nonprotein thiol content in rat lymphocytes: Its relation
      with intracellular Zn2.
AB  - Cellular actions of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum
      sensing molecule of bacteria, were studied on rat thymocytes using a flow
      cytometer with appropriate fluorescent dyes to elucidate the effects of ODHL on
      host cells. A bell-shaped concentration-response relation was observed in the
      ODHL-induced changes in cellular glutathione content ([GSH]i). ODHL concentration
      dependently increased intracellular Zn2+ levels ([Zn2+]i) and cellular O2-
      content ([O2-]i). The bell-shaped relation induced by ODHL can be explained as
      follows: a low concentration of ODHL is expected to induce moderate oxidative
      stress that intracellularly releases Zn2+ by converting thiols to disulfides. A
      slight elevation of [Zn2+]i may increase the [GSH]i. On the other hand, it is
      likely that a high concentration of ODHL causes severe oxidative stress that
      further causes both the decrease in [GSH]i and the increase in [Zn2+]i. Excessive
      increase in [Zn2+]i may augment oxidative stress that further decreases the
      [GSH]i. Other notable actions induced by ODHL included the elevation of [Zn2+]i
      by Zn2+ influx and the increase in [GSH]i under Zn2+-free conditions. Therefore,
      it is suggested that ODHL elicits diverse actions on host cells.

PMID- 29223569
TI  - Isolated mangiferin and naringenin exert antidiabetic effect via PPARgamma/GLUT4
      dual agonistic action with strong metabolic regulation.
AB  - In this study, we isolated two compounds from the leaves of Salacia oblonga (SA1,
      mangiferin and SA2, naringenin), and their structures were confirmed by infrared
      spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and mass
      spectrometry. SA1 and SA2 were orally administered to streptozotocin-induced
      diabetic rats at 50 and 100 mg/kg daily for 15 days. Blood glucose level, serum
      lipid profile, oxidative stress parameters, histopathology, docking, molecular
      parameters, and NMR-based metabolic perturbation studies were performed to
      investigate the pharmacological activities of SA1 and SA2. Results suggested that
      both compounds reduced blood glucose level, restored body weight, and normalized
      lipid concentrations in the serum and oxidative stress biomarkers in the liver
      and pancreas. In addition, the docking study on several diabetes-associated
      targets revealed that both compounds had a strong binding affinity towards
      peroxisome proliferator-activated receptor gamma (PPARgamma) and glucose
      transporter type 4 (GLUT4). Further real-time reverse transcription polymerase
      chain reaction and western blot analyses were performed to confirm the gene and
      protein expression levels of PPARgamma and GLUT4 in the pancreatic tissues. Data
      obtained from the molecular studies showed that both compounds exhibited
      antidiabetic effects through dual activation of PPARgamma/GLUT4 signaling
      pathways. Finally, the NMR-based metabolic studies showed that both compounds
      normalized the diabetogenic metabolites in the serum. Altogether, we concluded
      that SA1 and SA2 might be potential antidiabetic lead compounds for future drug
      development.

PMID- 29223570
TI  - Regulation and role of nuclear factor-E2-related factor 2 (Nrf2) in multidrug
      resistance of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) chemoresistance, which is regarded as a kind of
      stress management reaction to chemotherapy drugs, severely hinders the therapy
      outcomes of HCC treatment. Stress management is generally achieved by activating
      certain signal pathways and chemical factors, among which, nuclear factor-E2
      related factor2 (Nrf2) is a key factor in HCC chemoresistance formation. Nrf2 is
      a nuclear factor that coordinates the induction and expression of a battery of
      genes encoding cytoprotective proteins when participating in the Nrf2antioxidant
      response element (Nrf2/ARE) pathway, which is one of the most important
      intracellular antioxidant stress pathways. This review summarizes the recent
      understanding of the involvement of Nrf2 in the chemoresistance of liver cancer,
      its target proteins, expression regulation and potential Nrf2 inhibitors that
      sensitize chemotherapy drugs in HCC.

PMID- 29223571
TI  - Novel nitroaromatic compound activates autophagy and apoptosis pathways in HL60
      cells.
AB  - N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a
      nitroaromatic bioreducible compound with cytotoxic effects in cancer cell lines.
      The aim of this work was to investigate the molecular mechanisms involved in cell
      death promoted by NBCN in HL60 cells. We observed that NBCN treatment increased
      intracellular ROS and reduced mitochondria membrane potential (DeltaPsim). NBCN
      treatment also induced morphological changes, phosphatidylserine exposure, cell
      cycle arrest in G2/M-phase, DNA condensation and fragmentation, but it did not
      show cytotoxic effects on normal human peripheral blood mononuclear cells
      (PBMCs). NBCN-induced caspase 3- and 9-dependent DNA fragmentation, which was
      blocked by pretreatment with the broad-spectrum caspase inhibitor, z-VAD-fmk.
      Flow cytometry analysis demonstrated that NBCN also increased of the number of
      autophagic vesicles in HL60 cells, which was not observed when cells were pre
      treated with bafilomycin A1. Taken together, these results indicate that NBCN
      triggered the mitochondrial apoptotic pathway and led to the onset of autophagic
      cell death, which contributed to its cytotoxic effects.

PMID- 29223572
TI  - Curcumin ameliorates the in vitro efficacy of carfilzomib in human multiple
      myeloma U266 cells targeting p53 and NF-kappaB pathways.
AB  - Multiple myeloma (MM) is a malignant B-cell neoplasm with accumulation of
      malignant plasma cells in bone marrow. Pharmacological therapy improves response
      frequency even if with various associated toxicities. Herein, we investigated if
      combination of curcumin with carfilzomib (CFZ) can induce a better cytotoxic
      effect on in vitro cultured U266 cells. Cell viability data showed that curcumin
      significantly ameliorates CFZ cytotoxic effect. Furthermore, curcumin alone did
      not affect proteasome at the tested dose, confirming the involvement of different
      mechanisms in the observed effects. U266 cells exposure to curcumin or CFZ
      increased reactive species (RS) levels, although their production did not appear
      further potentiated following drugs combination. Interestingly, NF-kappaB nuclear
      accumulation was reduced by treatment with CFZ or curcumin, and was more deeply
      decreased in cells treated with CFZ-curcumin combinations, very likely due to the
      different mechanisms through which they target NF-kappaB. Our results confirmed
      the induction of p53/p21 axis and G0/G1 cell cycle arrest in anticancer
      activities of both drugs, an effect more pronounced for the CFZ-curcumin tested
      combinations. Furthermore, curcumin addition enhanced CFZ proapoptotic effect.
      These findings evidence that curcumin can ameliorate CFZ efficacy, and lead us to
      hypothesize that this effect might be useful to optimize CFZ therapy in MM
      patients.

PMID- 29223573
TI  - Biocompatibility of designed MicNo-ZnO particles: Cytotoxicity, genotoxicity and
      phototoxicity in human skin keratinocyte cells.
AB  - Recently, designed platelet shaped micron particles that are composed of nano
      primary particles, called MicNo (=Micron+naNo) particles, have been developed to
      exploit the benefits of nano size, while removing the adverse effects of
      nanoparticles. It has been shown that MicNo-ZnO particles exhibit both micron and
      nanosized particle characteristics. Although physical and chemical properties of
      MicNo-ZnO particles have been studied, their biocompatibility has not yet been
      evaluated. Accordingly, the research objective of this study was to evaluate in
      vitro cytotoxicity, genotoxicity and phototoxicity behaviors of designed MicNo
      ZnO particles over human epidermal keratinocyte (HaCaT) cells. MicNo-ZnO
      particles exhibit much less cytotoxicity with IC50 concentrations between 40 and
      50MUg/ml, genotoxicity above 40MUg/ml and lower photo genotoxicity under UVA on
      HaCaT than the ZnO nanoparticles. Although their chemistries are the same, the
      source of this difference in toxicity values may be attributed to size
      differences between the particles that are probably due to their ability to
      penetrate into the cells. In the present study, the expansive and detailed in
      vitro toxicity tests show that the biocompatibility of MicNo-ZnO particles is
      much better than that of the ZnO nanoparticles. Consequently, MicNo-ZnO particles
      can be considered an important active ingredient alternative for sunscreen
      applications due to their safer characteristics with respect to ZnO
      nanoparticles.

PMID- 29223574
TI  - Evaluation of the effects of antiepileptic drugs on folic acid uptake by human
      placental choriocarcinoma cells.
AB  - Folate status during pregnancy is important for fetal development and health. The
      placenta plays an important role in supplying the fetus with folate. Most women
      with epilepsy continue their medication during pregnancy. In the present study,
      we aimed to evaluate the effects of 16 antiepileptic drugs, clinically used for
      treatment of epilepsy, on folic acid uptake in two in vitro placental models,
      BeWo and JEG-3 cells. Short-term exposure to antiepileptic drugs had no effects
      on [3H]-folic acid uptake by BeWo cells. However, long-term exposure (24h) to
      valproic acid (VPA) increased [3H]-folic acid uptake by BeWo and JEG-3 cells. VPA
      treatment for 24h increased folate receptor-alpha (FRalpha) and proton-coupled
      folate transporter (PCFT) mRNA expression; however, it did not affect reduced
      folate carrier expression. These results suggested that the increase in folic
      acid uptake after exposure to VPA can be attributed to the induction of FRalpha
      and PCFT expression. Furthermore, the present study showed that exposure to
      clinical concentrations of oxcarbazepine and stiripentol reduced the viability of
      BeWo cells. Therefore, the findings of the present study may contribute to better
      understanding of the mechanisms of toxicity of antiepileptic drugs, and
      estimation of their potential risk to fetus.

PMID- 29223575
TI  - A comparison between inhalational (Desflurane) and total intravenous anaesthesia
      (Propofol and dexmedetomidine) in improving postoperative recovery for morbidly
      obese patients undergoing laparoscopic sleeve gastrectomy: A double-blinded
      randomised controlled trial.
AB  - STUDY OBJECTIVE: Laparoscopic sleeve gastrectomy is commonly performed under
      total intravenous anaesthesia (TIVA) or balanced anaesthesia using an intravenous
      and inhalation agent. It is still unclear which anaesthesia regimen is better for
      this group of patients. The present study has been conducted to compare the use
      of the inhalation anaesthesia technique using desflurane with the TIVA technique,
      using propofol and dexmedetomidine. DESIGN: Prospective, randomised, double
      blinded study. SETTING: Menoufia Univeristy Hospital. PATIENTS: This randomised
      trial was carried out on 100 morbidly obese patients undergoing laparoscopic
      sleeve gastrectomy. The patients were randomised into two equally sized groups;
      one group received the inhalation anaesthesia technique and the other received
      the TIVA technique. INTERVENTIONS: All patients received general anaesthesia,
      which was induced by propofol, remifentanil, and rocuronium. Anaesthesia was
      maintained using desflurane in oxygen air mixture in the inhalation group, whilst
      anaesthesia was maintained by intravenous infusion of propofol and
      dexmedetomidine in the TIVA group. MEASUREMENTS: Intra-operative vital signs,
      anaesthesia recovery time, postoperative nausea and vomiting, pain score, post
      anaesthetic care unit (PACU) stay time, total first 24h post-operative analgesic
      needs and the onset of first bowel movement were recorded. Main results The TIVA
      group had lower intra-operative heart rates and mean arterial blood pressure
      (P<0.0001). The TIVA group also had a lower post-operative visual analogue score
      for pain assessment (VAS) (P<0.0001), lower total analgesic requirements
      (P<0.0001), a lower incidence of nausea (P=0.01) and vomiting (P=0.03), and
      shorter PACU stays (P=0.01). There was no significant difference between groups
      with regard to the onset of bowel movement (P=0.16). CONCLUSIONS: TIVA using
      propofol and dexmedetomidine is a better anaesthetic regimen than inhalation
      anaesthesia using desflurane for laparoscopic sleeve gastrectomy in morbidly
      obese patients. The TIVA technique provided better postoperative recovery with
      fewer postoperative side effects and analgesic requirements. CLINICAL TRIAL
      REGISTERY NUMBER: NCT03029715.

PMID- 29223576
TI  - Uptake of iron (III)-ethylenediamine-N,N,N',N'-tetraacetic acid complex by
      phosphatidylcholine lipid film: Part I. Effect of bulk pH.
AB  - We studied a ternary solutes aqueous solution of NaOH, iron (III)-ethylenediamine
      N,N,N',N'-tetraacetic acid complex (Fe-edta), and 1,2-diheptanoyl-sn-glycero-3
      phosphatidylcholine (DHPC)/air interface system to clarify the interactions
      between iron complexes and lipids with a phosphatidylcholine head group. The
      solution surface tension and pH were measured as functions of the total molality
      of NaOH, Fe-edta and DHPC, and the mole fractions of NaOH and DHPC. Rigorous
      thermodynamic equations were derived, in which the overall proton dissociation
      equilibria of Fe-edta and DHPC were taken into consideration, and applied to
      experimental data to obtain phase diagram of adsorption. It was found that (1)
      adsorption of Fe-edta at the solution/air interface with a DHPC monolayer was
      about 50-130 times higher than that without a DHPC monolayer and (2) when the
      bulk mole fraction of NaOH was high, Fe-edta tended to be expelled from the
      adsorbed film. The last finding suggests that the ambient pH significantly
      affects passive transport of the iron complex through a phospholipid-containing
      membrane into the cell interior.

PMID- 29223577
TI  - Race as a predictor of patient preferences for biopsy result communication.

PMID- 29223578
TI  - Generational influence on patient learning preferences in dermatology.

PMID- 29223579
TI  - Design considerations for handling dropouts in anti-depressant drug trials.
AB  - BACKGROUND: In clinical trials, statistical analysis often requires certain
      assumptions about missing data for a valid statistical inference. If the dropout
      rate is high, a wrong assumption about the missing data may compromise the
      validity of statistical inferences. PURPOSE: To mitigate the high dropout rates
      commonly observed in psychiatry clinical trials, we consider two design
      approaches for short-term controlled trials submitted in support of marketing
      applications for drug products for the major depressive disorder (MDD)
      indication: (1) shortening the trial duration and (2) treating time to treatment
      discontinuation as an alternative primary efficacy endpoint. METHODS: Subject
      level efficacy data from 45 trials for drugs approved for an MDD indication
      between 1997 and 2014 were collected. We analyzed change from baseline in
      Hamilton Depression Rating Scale (HAMD-17) total score using the mixed model
      repeated measures approach. We compared the least squares means and the 95%
      confidence intervals of the treatment effect among three different trial
      durations, 4, 6, and 8weeks. We considered two definitions of discontinuation:
      (i) all-cause discontinuation, (ii) discontinuation due to lack of efficacy. We
      compared the two-sided log-rank p-values with the p-values from the protocol
      specified primary analysis. CONCLUSIONS: Our findings suggest that MDD trials in
      the acute setting may be shortened to 6weeks provided that the treatment
      difference between drug and placebo on HAMD-17 total score reaches approximately
      2units at Week 6. However, our exploratory analyses of available data do not
      support the use of time to treatment discontinuation as an alternative primary
      efficacy endpoint.

PMID- 29223580
TI  - Modeling HIV disease progression and transmission at population-level: The
      potential impact of modifying disease progression in HIV treatment programs.
AB  - INTRODUCTION: Mathematical models that incorporate HIV disease progression
      dynamics can estimate the potential impact of strategies that delay HIV disease
      progression and reduce infectiousness for persons not on antiretroviral therapy
      (ART). Suppressive treatment of HIV-positive persons co-infected with herpes
      simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV
      viral load, but the impact of partially-suppressive valacyclovir relative to
      fully-suppressive ART on population HIV transmission has not been estimated.
      METHODS: We modeled HIV disease progression as a function of changes in viral
      load and CD4 count over time among ART naive persons. The disease progression
      Markov model was nested within a dynamic model of HIV transmission at population
      level. We assumed that valacyclovir reduced HIV viral load by 1.23 log
      copies/MUL, and that persons treated with valacyclovir initiated ART more rapidly
      when their CD4 fell below 500 due to retention in HIV care. We estimated the
      potential impact of valacyclovir on onward transmission of HIV in three scenarios
      of different ART and valacyclovir population coverage. RESULTS: The average
      duration of HIV infection was 9.5 years. The duration of disease before reaching
      CD4 200cells/MUL was 2.53 years longer for females than males. Relative to a
      baseline of ART initiation at CD4<=500cells/MUL, the valacyclovir scenario
      resulted in 167,000 fewer HIV infections over ten years, with an incremental cost
      effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat
      scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV
      infections at an ICER of $2822 and $812 per HIV infection averted and QALY
      gained, respectively. CONCLUSION: Even when compared with valacyclovir
      suppression, a drug that reduces HIV viral load, universal treatment for HIV is
      the optimal strategy for averting new infections and increasing public health
      benefit. Universal HIV treatment would most effectively and efficiently reduce
      the HIV burden.

PMID- 29223581
TI  - Toward new forms of meal sharing? Collective habits and personal diets.
AB  - This article sheds light on the fact that the commensality remains a fundamental
      aspect of eating in French culture. However, at the same time, the expansion of
      the individualisation and medicalisation of the act of eating during the latest
      decades impacted the social representations of food. We will first place dietary
      practices into a general context in which the relationship to food tends to be
      individualised and in which health-related issues remain an important aspect of
      the discourse about food on internet. Secondly, we will examine how these
      practices are (in)compatible with the defining dimensions of the French food
      model, in particular those relating to commensality (the practice of eating
      together) and food sharing. It seems that although a personalised diet restricts
      the objective possibilities of food sharing, it is still central in
      representations of food and, in some cases, leads to the emergence of associated
      practices to introduce new forms of social eating behaviours, such as those made
      possible by the spread of the Internet.

PMID- 29223582
TI  - Looking for relationships between the populations of Dothistroma septosporum in
      northern Europe and Asia.
AB  - Dothistroma septosporum, a notorious pine needle pathogen with an unknown
      historical geographic origin and poorly known distribution pathways, is nowadays
      found almost in all areas inhabited by pines (Pinus spp.). The main aim of this
      study was to determine the relationship between North European and East Asian
      populations. In total, 238 Eurasian D. septosporum isolates from 11 countries,
      including 211 isolates from northern Europe, 16 isolates from Russian Far East
      and 11 isolates from Bhutan were analysed using 11 species-specific
      microsatellite and mating type markers. The most diverse populations were found
      in northern Europe, including the Baltic countries, Finland and European Russia.
      Notably, D. septosporum has not caused heavy damage to P. sylvestris in northern
      Europe, which may suggest a long co-existence of the host and the pathogen. No
      indication was obtained that the Russian Far East or Bhutan could be the
      indigenous area of D. septosporum, as the genetic diversity of the fungus there
      was low and evidence suggests gene flow from northern Europe to Russian Far East.
      On the western coast of Norway, a unique genetic pattern was observed, which
      differed from haplotypes dominating other Fennoscandian populations. As an agent
      of dothistroma needle blight, only D. septosporum was documented in northern
      Europe and Asia, while D. pini was found in Ukraine and Serbia.

PMID- 29223584
TI  - Tuberculosis eradication: renewed commitment and global investment required.

PMID- 29223585
TI  - Influence of dietary nitrate food forms on nitrate metabolism and blood pressure
      in healthy normotensive adults.
AB  - Inorganic nitrate (NO3-) supplementation has been shown to improve cardiovascular
      health indices in healthy adults. The purpose of this study was to investigate
      how the vehicle of NO3- administration can influence NO3- metabolism and the
      subsequent blood pressure response. Ten healthy males consumed an acute equimolar
      dose of NO3- (~5.76 mmol) in the form of a concentrated beetroot juice drink (BR;
      55 mL), a non-concentrated beetroot juice drink (BL; 456 mL) and a solid beetroot
      flapjack (BF; 60 g). A drink containing soluble beetroot crystals (BC; ~1.40 mmol
      NO3-) and a control drink (CON; 70 mL deionised water) were also ingested. BP and
      plasma, salivary and urinary [NO3-] and [NO2-] were determined before and up to
      24 h after ingestion. All NO3--rich vehicles elevated plasma, salivary and
      urinary nitric oxide metabolites compared with baseline and CON (P<0.05). The
      peak increases in plasma [NO2-] were greater in BF (371 +/- 136 nM) and BR (369
      +/- 167 nM) compared to BL (283 +/- 93 nM; all P<0.05) and BC (232 +/- 51 nM).
      BR, but not BF, BL and BC, reduced systolic (~5 mmHg) and mean arterial pressure
      (~3-4 mmHg; P<0.05), whereas BF reduced diastolic BP (~4 mmHg; P < 0.05).
      Although plasma [NO2-] was elevated in all conditions, the consumption of a
      small, concentrated NO3--rich fluid (BR) was the most effective means of reducing
      BP. These findings have implications for the use of dietary NO3-supplements when
      the main objective is to maintain or improve indices of cardiovascular health.

PMID- 29223586
TI  - Reduction in human Lyme neuroborreliosis associated with a major epidemic among
      roe deer.
AB  - Lyme neuroborreliosis is the most severe clinical manifestation of Lyme
      borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme
      borreliosis seems to be stabilising. This is not the case on the island of Funen,
      Denmark, where the number of human Lyme neuroborreliosis cases has markedly
      declined throughout the last decade. We propose the reason for the decline is a
      major epidemic among roe deer, killing almost half of their population, resulting
      in a reduction in the tick population which make it less likely to get a tick
      bite and therefore to contract Lyme neuroborreliosis. This is the first time such
      a relationship is described as a naturally occurring phenomenon in Europe.

PMID- 29223583
TI  - The global burden of tuberculosis: results from the Global Burden of Disease
      Study 2015.
AB  - BACKGROUND: An understanding of the trends in tuberculosis incidence, prevalence,
      and mortality is crucial to tracking of the success of tuberculosis control
      programmes and identification of remaining challenges. We assessed trends in the
      fatal and non-fatal burden of tuberculosis over the past 25 years for 195
      countries and territories. METHODS: We analysed 10 691 site-years of vital
      registration data, 768 site-years of verbal autopsy data, and 361 site-years of
      mortality surveillance data using the Cause of Death Ensemble model to estimate
      tuberculosis mortality rates. We analysed all available age-specific and sex
      specific data sources, including annual case notifications, prevalence surveys,
      and estimated cause-specific mortality, to generate internally consistent
      estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian
      meta-regression tool. We assessed how observed tuberculosis incidence,
      prevalence, and mortality differed from expected trends as predicted by the Socio
      demographic Index (SDI), a composite indicator based on income per capita,
      average years of schooling, and total fertility rate. We also estimated
      tuberculosis mortality and disability-adjusted life-years attributable to the
      independent effects of risk factors including smoking, alcohol use, and diabetes.
      FINDINGS: Globally, in 2015, the number of tuberculosis incident cases (including
      new and relapse cases) was 10.2 million (95% uncertainty interval 9.2 million to
      11.5 million), the number of prevalent cases was 10.1 million (9.2 million to
      11.1 million), and the number of deaths was 1.3 million (1.1 million to 1.6
      million). Among individuals who were HIV negative, the number of incident cases
      was 8.8 million (8.0 million to 9.9 million), the number of prevalent cases was
      8.9 million (8.1 million to 9.7 million), and the number of deaths was 1.1
      million (0.9 million to 1.4 million). Annualised rates of change from 2005 to
      2015 showed a faster decline in mortality (-4.1% [-5.0 to -3.4]) than in
      incidence (-1.6% [-1.9 to -1.2]) and prevalence (-0.7% [-1.0 to -0.5]) among HIV
      negative individuals. The SDI was inversely associated with HIV-negative
      mortality rates but did not show a clear gradient for incidence and prevalence.
      Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV
      negative tuberculosis burden than expected given their SDI. Alcohol use accounted
      for 11.4% (9.3-13.0) of global tuberculosis deaths among HIV-negative individuals
      in 2015, diabetes accounted for 10.6% (6.8-14.8), and smoking accounted for 7.8%
      (3.8-12.0). INTERPRETATION: Despite a concerted global effort to reduce the
      burden of tuberculosis, it still causes a large disease burden globally.
      Strengthening of health systems for early detection of tuberculosis and
      improvement of the quality of tuberculosis care, including prompt and accurate
      diagnosis, early initiation of treatment, and regular follow-up, are priorities.
      Countries with higher than expected tuberculosis rates for their level of
      sociodemographic development should investigate the reasons for lagging behind
      and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes
      could also substantially reduce the burden of tuberculosis. FUNDING: Bill &
      Melinda Gates Foundation.

PMID- 29223587
TI  - Molecular characterization of Theileria equi in horses from the state of Rio de
      Janeiro, Brazil.
AB  - Theileria equi is one of the etiologic agents of the equine piroplasmosis. This
      infectious disease is transmitted by ticks and is a worldwide problem in the
      international horse movement. The 18S rRNA gene of T. equi is often used for
      genotyping and phylogenetic purpose. This study aimed to analyze the degree of
      the heterogeneity of the 18S rRNA gene of T. equi in horses from the state of Rio
      de Janeiro, Brazil. The complete T. equi 18S rRNA sequences were obtained from
      twenty naturally infected horses. The PCR amplicons were cloned and sequenced.
      The phylogenetic analyses were performed using a set of T. equi 18S rRNA
      sequences and other related organisms available in ARB-Silva database. There were
      twelve distinct T. equi 18S rRNA gene sequences circulating in horses in the
      state of Rio de Janeiro, Brazil. Monophyletic clades with 2% evolutionary
      divergence between clades and high bootstrap value were the support to divide T.
      equi sequences in three distinct clades. The sequences from this study grouped
      into clades I (70%, n=14/20) and II (30%, n=6/20). All of the T. equi sequences
      grouped within a node other than the theileriids. This study reported a clear
      division of two distinct genotypes of T. equi 18S rRNA sequences in state of Rio
      de Janeiro, Brazil, and it demonstrates that distinct isolates of T. equi can
      coexist in the same geographic region.

PMID- 29223588
TI  - (-)-9'-O-(alpha-l-Rhamnopyranosyl)lyoniresinol from Lespedeza cuneata suppresses
      ovarian cancer cell proliferation through induction of apoptosis.
AB  - Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae), known as Chinese bushclover
      or sericea lespedeza, has been used in traditional medicine to treat diabetes,
      hematuria, and insomnia, and it has been reported that bioactive compounds from
      L. cuneata possess various pharmacological properties. However, there has been no
      study to determine the active compounds from L. cuneata with potential activity
      against ovarian cancer. This study aimed to isolate cytotoxic compounds from L.
      cuneata and identify the molecular mechanisms underlying the apoptosis pathway in
      ovarian cancer cells. Based on cytotoxic activity identified in the screening
      test, chemical investigation of the active fraction of L. cuneata led to the
      isolation of nine compounds including four lignanosides (1-4), three flavonoid
      glycosides (5-7), and two phenolics (8-9). Cytotoxicity and the molecular
      mechanism were examined by methyl thiazolyl tetrazolium (MTT) assay and Western
      blot analysis. Of the isolated compounds, (-)-9'-O-(alpha-l
      rhamnopyranosyl)lyoniresinol (3) demonstrated the strongest effect in suppressing
      A2780 human ovarian carcinoma cell proliferation in a dose-dependent manner, with
      an IC50 value of 35.40 +/- 2.78 MUM. Control A2780 cells had normal morphology,
      whereas cell blebbing, shrinkage, and condensation were observed after treatment
      with compound 3. Western blotting analysis showed that compound 3 inhibited A2780
      human ovarian cancer cell viability by activating caspase-8, caspase-3, and PARP,
      which contributed to apoptotic cell death. These results suggest that (-)-9'-O
      (alpha-l-rhamnopyranosyl)lyoniresinol (3) has potent anticancer activities
      against A2780 human ovarian carcinoma cells through the extrinsic apoptotic
      pathway. Therefore, (-)-9'-O-(alpha-l-rhamnopyranosyl)lyoniresinol is an
      excellent candidate for the development of novel chemotherapeutics.

PMID- 29223589
TI  - Breakthroughs in neuroactive steroid drug discovery.
AB  - Endogenous and synthetic neuroactive steroids (NASs) or neurosteroids are
      effective modulators of multiple signaling pathways including receptors for the
      gamma-aminobutyric acid A (GABAA) and glutamate, in particular N-methyl-d
      aspartate (NMDA). These receptors are the major inhibitory and excitatory
      neurotransmitters in the central nervous system (CNS), and there is growing
      evidence suggesting that dysregulation of neurosteroid production plays a role in
      numerous neurological disorders. The significant unmet medical need for treatment
      of CNS disorders has increased the interest for these types of compounds. In this
      review, we highlight recent progress in the clinical development of NAS drug
      candidates, in addition to preclinical breakthroughs in the identification of
      novel NASs, mainly for GABAA and NMDA receptor modulation.

PMID- 29223590
TI  - Recent encounters with atropisomerism in drug discovery.
AB  - Atropisomerism is stereochemistry arising from restricted bond rotation that
      creates a chiral axis. Atropisomers are subject to time-dependent inversion of
      chirality via bond rotation, a property which in drug molecules introduces
      complexity and challenges for drug discovery and development processes. Greater
      recognition of the occurrence of atropisomerism and improved characterization
      techniques have helped medicinal chemists successfully advance atropisomeric drug
      molecules. This review provides recent examples of atropisomerism encountered in
      medicinal chemistry efforts and the strategies used to address the accompanying
      challenges.

PMID- 29223591
TI  - Mild hypothermia protects hippocampal neurons from oxygen-glucose deprivation
      injury through inhibiting caspase-3 activation.
AB  - Mild hypothermia (MH) is thought to be one of the most effective therapeutic
      methods to treat hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA).
      However, its precise mechanisms remain unclear. In this research, hippocampal
      neurons were cultured and treated with mild hypothermia and Ac-DEVD-CHO after
      oxygen-glucose deprivation (OGD). The activity of caspase-3 was detected, in
      order to find the precise concentration of Ac-DEVD-CHO with the same protective
      role in OGD injury as MH treatment. Western blot and immunofluorescence staining
      were conducted to analyze the effects of MH and Ac-DEVD-CHO on the expressions of
      caspase-3, caspase-8, and PARP. The neuronal morphology was observed with an
      optical microscope. The lactic acid dehydrogenase (LDH) release rate, neuronal
      viability, and apoptotic rate were also detected. We found that MH (32  degrees
      C) and Ac-DEVD-CHO (5.96 MUMol/L) had equal effects on blocking the activation of
      caspase-3 and the OGD-induced cleavage of PARP, but neither had any effect on the
      activation of caspase-8, which goes on to activate caspase-3 in the apoptotic
      pathway. Meanwhile, both MH and Ac-DEVD-CHO had similar effects in protecting
      cell morphology, reducing LDH release, and inhibiting OGD-induced apoptosis in
      neurons. They also similarly improved neuronal viability after OGD. In
      conclusion, caspase-3 serves as a key intervention point of the key modulation
      site or regulatory region in MH treatment that protects neuronal apoptosis
      against OGD injury. Inhibiting the expression of caspase-3 had a protective
      effect against OGD injury in MH treatment, and caspase-3 activation could be
      applied to evaluate the neuroprotective effectiveness of MH on HIE.

PMID- 29223592
TI  - Concentration dependence of the cell membrane permeability to cryoprotectant and
      water and implications for design of methods for post-thaw washing of human
      erythrocytes.
AB  - For more than fifty years the human red blood cell (RBC) has been a widely
      studied model for transmembrane mass transport. Existing literature spans myriad
      experimental designs with varying results and physiologic interpretations. In
      this review, we examine the kinetics and mechanisms of membrane transport in the
      context of RBC cryopreservation. We include a discussion of the pathways for
      water and glycerol permeation through the cell membrane and the implications for
      mathematical modeling of the membrane transport process. In particular, we
      examine the concentration dependence of water and glycerol transport and provide
      equations for estimating permeability parameters as a function of concentration
      based on a synthesis of literature data. This concentration-dependent transport
      model may allow for design of improved methods for post-thaw removal of glycerol
      from cryopreserved blood. More broadly, the consideration of the concentration
      dependence of membrane permeability parameters may be important for other cell
      types as well, especially for design of methods for equilibration with the highly
      concentrated solutions used for vitrification.

PMID- 29223593
TI  - Far cortical locking and active plating concepts: New revolutions of fracture
      fixation in the waiting?

PMID- 29223594
TI  - Femoral neck fractures after removal of hardware in healed trochanteric
      fractures.
AB  - INTRODUCTION: Hardware removal in healed trochanteric fractures (TF) in the
      absence of infection or significant mechanical complications is rarely indicated.
      However, in patients with persistent pain, prominent material and discomfort in
      the activities of daily living, the implant is eventually removed. Publications
      of ipsilateral femoral neck fracture after removal of implants from healed
      trochanteric fractures (FNFARIHTF) just because of pain or discomfort are rare.
      The purpose of this systematic review of the literature is to report on the
      eventual risk factors, the mechanisms, the clinical presentation, and frequency,
      and to pay special emphasis in their prevention. MATERIALS AND METHODS: A
      comprehensive review of the literature was undertaken using the PRISMA guidelines
      with no language restriction. Case reports of FNFARIHTF and series of TF with
      cases of FNFARIHTF due to pain or discomfort published between inception of
      journals to December 2016 were eligible for inclusion. Relevant information was
      divided in two parts. Part I included the analysis of cases of FNFARIHTF, with
      the objective of establishing the eventual risk factors, mechanisms and
      pathoanatomy, clinical presentation and diagnosis, treatment and prevention. Part
      II analyzed series of TF which included cases of FNFARIHTF for assessing the
      incidence of femoral neck fractures in this condition. RESULTS: Overall 24
      publications with 45 cases of FNFARIHTF met the inclusion criteria. We found that
      the only prevalent factors for FNFARIHTF were: 1) preexisisting systemic
      osteoporosis, as most patients were older and elder females, with lower bone
      mineral density and bone mass; 2) local osteoporosis as a result of preloading by
      the fixation device in the femoral neck, leading to stress protection, reducing
      the strain at the neck, and increasing bone loss and weakness; and 3) the removal
      of hardware from the femoral neck, with reduction of the failure strength of the
      neck. The femoral neck fractures were spontaneous, i.e. not related to trauma or
      fall, in 87.5% of the cases, mostly subcapital, and with no prevalence between
      displaced and undisplaced fractures. The clinical presentation was that of a
      spontaneous fracture, and most of the patients consulted because of hip pain and
      presented in the emergency room walking by themselves which led to delayed
      diagnosis in several instances. Radiological diagnosis was mostly with
      radiographs, though in some cases CT scans or MRI were necessary. The overall
      median incidence of this complication was 14.5% after hardware removal because of
      pain or discomfort in healed trochanteric fractures. CONCLUSION: The risk factors
      for FNFARIHTF seem to be preexisisting systemic osteoporosis, local osteoporosis
      as a result of preloading by the fixation device in the femoral neck, and the
      removal of hardware from the femoral neck, with reduction of the strength of the
      neck. The clinical presentation may be obscure as most of the patients complain
      of hip pain of some days or weeks, and arrive in the hospital walking. Therefore,
      the attending physician should be alert in order to request the appropriate
      radiological investigation and if this is not clear CT scan or MRI should be done
      in order to diagnose promptly these "spontaneous" fractures. Treatment should be
      replacement surgery in most cases; however, there is some place for internal
      fixation especially in undisplaced fractures or younger patients. The occurrence
      of the femoral neck fracture after hardware removal may be prevented with re
      osteosynthesis and the use of bone chips or bone substitutes. Finally, the
      relatively high incidence of this complication should alert orthopaedic surgeons
      to reduce the removal of hardware in healed trochanteric fractures to very
      selected cases.

PMID- 29223595
TI  - Modulation of cartilage's response to injury: Can chondrocyte apoptosis be
      reversed?
AB  - Osteoarthritis is characterized by a chronic, progressive and irreversible
      degradation of the articular cartilage associated with joint inflammation and a
      reparative bone response. More than 100 million people are affected by this
      condition worldwide with significant health and welfare costs. Our available
      treatment options in osteoarthritis are extremely limited. Chondral or
      osteochondral grafts have shown some promising results but joint replacement
      surgery is by far the most common therapeutic approach. The difficulty lies on
      the limited regeneration capacity of the articular cartilage, poor blood supply
      and the paucity of resident progenitor stem cells. In addition, our poor
      understanding of the molecular signalling pathways involved in the senescence and
      apoptosis of chondrocytes is a major factor restricting further progress in the
      area. This review focuses on molecules and approaches that can be implemented to
      delay or even rescue chondrocyte apoptosis. Ways of modulating the physiologic
      response to trauma preventing chondrocyte death are proposed. The use of several
      cytokines, growth factors and advances made in altering several of the
      degenerative genetic pathways involved in chondrocyte apoptosis and degradation
      are also presented. The suggested approaches can help clinicians to improve
      cartilage tissue regeneration.

PMID- 29223596
TI  - Presence and persistence of the amnesic shellfish poisoning toxin, domoic acid,
      in octopus and cuttlefish brains.
AB  - Domoic acid (DA) is a neurotoxin that causes degenerative damage to brain cells
      and induces permanent short-term memory loss in mammals. In cephalopod mollusks,
      although DA is known to accumulate primarily in the digestive gland, there is no
      knowledge whether DA reaches their central nervous system. Here we report, for
      the first time, the presence of DA in brain tissue of the common octopus (Octopus
      vulgaris) and the European cuttlefish (Sepia officinalis), and its absence in the
      brains of several squid species (Loligo vulgaris, L. forbesi and Todarodes
      sagittatus). We argue that such species-specific differences are related to their
      different life strategies (benthic/nektobenthic vs pelagic) and feeding
      ecologies, as squids mainly feed on pelagic fish, which are less prone to
      accumulate phycotoxins. Additionally, the temporal persistence of DA in octopus'
      brain reinforces the notion that these invertebrates can selectively retain this
      phycotoxin. This study shows that two highly-developed invertebrate species, with
      a complex central nervous system, where glutamatergic transmission is involved in
      vertebrate-like long-term potentiation (LTP), have the ability of retaining and
      possibly tolerating chronic exposure to DA, a potent neurotoxin usually acting at
      AMPA/kainate-like receptors. Here, we filled a gap of information on whether
      cephalopods accumulated this neurotoxin in brain tissue, however, further studies
      are needed to determine if these organisms are neurally or behaviourally impaired
      by DA.

PMID- 29223597
TI  - Missed opportunities for HPV immunization among young adult women.
AB  - BACKGROUND: Despite the availability of a safe and efficacious vaccine against
      human papillomavirus, uptake of the vaccine in the United States is low. Missed
      clinical opportunities to recommend and to administer human papillomavirus
      vaccine are considered one of the most important reasons for its low uptake in
      adolescents; however, little is known about the frequency or characteristics of
      missed opportunities in the young adult (18-26 years of age) population.
      OBJECTIVE: The objective of the study was to assess both the rates of and the
      factors associated with missed opportunities for human papillomavirus
      immunization among young adult women who attended an urban obstetrics and
      gynecology clinic. STUDY DESIGN: In this cross-sectional study, medical records
      were reviewed for all women 18-26 years of age who were underimmunized (<3 doses)
      and who sought care from Feb. 1, 2013, to January 31, 2014, at an urban, hospital
      based obstetrics and gynecology clinic. A missed opportunity for human
      papillomavirus immunization was defined as a clinic visit at which the patient
      was eligible to receive the vaccine and a dose was due but not administered.
      Multivariable logistic regression was used to test associations between
      sociodemographic variables and missed opportunities. RESULTS: There were 1670
      vaccine-eligible visits by 1241 underimmunized women, with a mean of 1.3 missed
      opportunities/person. During the study period, 833 of the vaccine eligible women
      (67.1%) had at least 1 missed opportunity. Overall, the most common types of
      visits during which a missed opportunity occurred were postpartum visits (17%) or
      visits for either sexually transmitted disease screening (21%) or contraception
      (33%). Of the patients with a missed opportunity, 26.5% had a visit at which an
      injectable medication or a different vaccine was administered. Women who
      identified their race as black had higher adjusted odds of having a missed
      opportunity compared with white women (adjusted odds ratio, 1.61 [95% confidence
      interval, 1.08-2.41], P < .02). Women who reported a non-English- or non-Spanish
      preferred language had lower adjusted odds of having a missed opportunity
      (adjusted odds ratio, 0.25 [95% confidence interval, 0.07-0.87], P = .03). No
      other patient characteristics assessed in this study were significantly
      associated with having a missed opportunity. CONCLUSION: A majority of young
      adult women in this study had missed opportunities for human papillomavirus
      immunization, and significant racial disparity was observed. The greatest
      frequency of missed opportunities occurred with visits for either contraception
      or for sexually transmitted disease screening.

PMID- 29223598
TI  - Prognosis and treatment of positive peritoneal cytology in early endometrial
      cancer: matched cohort analyses from the National Cancer Database.
AB  - BACKGROUND: While positive peritoneal cytology is no longer included among the
      endometrial cancer staging criteria, Federation International de Gynecologie et
      Obstetrique recommends continued collection of pelvic washings for cytology to
      produce additional data that may be used to determine the significance of
      positive cytology for prognosis and treatment of endometrial cancer. OBJECTIVES:
      The objectives of the study was to validate that positive cytology is a predictor
      of decreased survival in early endometrial cancer and to test whether adjuvant
      chemotherapy for positive cytology is associated with increased survival. STUDY
      DESIGN: We performed an observational retrospective cohort analysis of the 2010
      2013 National Cancer Database including women with cytology status and Federation
      International de Gynecologie et Obstetrique stage IA-II endometrial cancer.
      Overall cohort and matched cohort survival analyses were performed with and
      without imputation of missing data. We also performed survival analyses of women
      with positive cytology grouped by chemotherapy exposure. Multivariable Cox
      proportional-hazards regressions were performed to adjust for possible
      confounders. A variety of sensitivity analyses, including robustness of results
      to possible unmeasured confounding, were reported. RESULTS: A total of 16,851
      women including 953 with positive cytology were included. Four-year overall
      survival was 79.5% (range, 76.2-83.0%) for women with stage I/II with positive
      cytology vs 92.2% (range, 91.5-92.9%), 83.3% (range, 81.6-84.9%), and 86.8%
      (range, 85.1-88.5%) for stage IA, IB, and II with negative cytology, respectively
      (P <= .001). Positive cytology was associated with decreased survival (hazard
      ratio [95% confidence interval], 1.85 [range, 1.54-2.21], P < .001). For women
      with Federation International de Gynecologie et Obstetrique grade 1/2
      endometrioid adenocarcinoma, the hazard of death associated with positive
      cytology was similar (hazard ratio [95% confidence interval], 1.85 [1.28-2.67], P
      < .001). Use of adjuvant chemotherapy by women with positive cytology was
      associated with increased survival (hazard ratio [95% confidence interval], 0.62
      [0.40-0.95], P = .03). CONCLUSION: Positive peritoneal cytology was associated
      with decreased overall survival of women with Federation International de
      Gynecologie et Obstetrique stage I/II endometrial cancer, including low-grade
      endometrioid endometrial cancer. Treatment of women with stage I/II endometrial
      cancer and positive cytology with adjuvant chemotherapy was associated with
      increased survival.

PMID- 29223600
TI  - Trans epsilon-viniferin is an amyloid-beta disaggregating and anti-inflammatory
      drug in a mouse primary cellular model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is marked by several cellular and molecular damage.
      Therefore, the therapeutic interest of multi-target molecules is increasingly
      justified. Polyphenols presenting multiple pharmacological effects would be more
      efficient. In this study, beneficial effects of trans epsilon-viniferin, a
      natural polyphenol were thus evaluated. This study reported that this stilbenoid
      (1) induced the disaggregation of amyloid beta (Abeta) peptide and (2) rescued
      inflammation in murine primary neuronal cultures. These both effects are higher
      than those of resveratrol, and so, trans epsilon-viniferin could be a good
      therapeutic multi-target candidate.

PMID- 29223599
TI  - Pharmacological intervention and abstinence in smokers undergoing cessation
      treatment: A psychophysiological study.
AB  - As a composite concept, negative affect comprises various aversive emotional
      experiences, such as irritability and nervousness. It is a critical motivational
      factor that helps maintain smoking behavior, and contributes significantly to
      smoking cessation failure as a core withdrawal symptom. Prior research has
      indicated an important role of nicotinic mechanisms in negative affect
      processing. The most effective smoking cessation medication, varenicline, targets
      nicotinic acetylcholine receptors (nAChRs) as a partial agonist, while another
      first-line cessation medication, bupropion, has shown antagonistic effects on
      nAChRs. Therefore, it is possible that both medications work to reduce smoking
      behavior through modulating negative affect processing. To evaluate this
      hypothesis, we examined the impact of varenicline tartrate and bupropion
      hydrochloride sustained-release on electrophysiological responses to affective,
      cigarette-related, and neutral cues before and during smoking cessation treatment
      in a randomized placebo-controlled clinical trial. The participants were 206
      smokers, a subset of 294 participants that were enrolled in a larger smoking
      cessation clinical trial who were randomly assigned to one medication group for
      12weeks. Orbicularis oculi (startle eyeblink response) and corrugator supercilii
      facial electromyographic (EMG) reactivity toward emotional pictures (i.e.,
      pleasant and unpleasant) in a picture-viewing task were measured before treatment
      and 2 and 6weeks after treatment was started. The startle and corrugator EMG
      activities increase with the exposure to unpleasant cues, and served as indices
      for negative emotional reactivity (NER). We found that after 6weeks, drug reduced
      startle-related NER in the varenicline group, but not in the bupropion or placebo
      group. Independent of medication treatment, lower baseline NER, as measured by
      the corrugator EMG activity, predicted a higher likelihood of smoking abstinence
      1 and 3months after quitting smoking. These findings indicate the important roles
      of varenicline in negative affect processing and negative emotional reactivity in
      the course of smoking cessation.

PMID- 29223601
TI  - Early coronary angiography and percutaneous coronary intervention are associated
      with improved outcomes after out of hospital cardiac arrest.
AB  - AIM: Early coronary angiography (CAG) and percutaneous coronary intervention
      (PCI) are associated with better outcomes in subjects resuscitated from out-of
      hospital cardiac arrest (OHCA). We sought to determine the relative contributions
      of early CAG and PCI to outcomes and adverse events after OHCA. METHODS: We
      analyzed 599 OHCA subjects from a prospective two-center registry. Hospital
      survival, functional outcomes and adverse events were compared between subjects
      undergoing early CAG (within 24h) with or without PCI and subjects not undergoing
      early CAG. We adjusted for propensity to perform early CAG and PCI and for post
      resuscitation illness severity and care. RESULTS: Early CAG subjects had improved
      rates of hospital survival (56.2% versus 31.0%, OR 2.85 [95% CI 2.04-4.00];
      p<0.0001) and better functional outcomes compared to no early CAG. Early PCI was
      associated with improved survival compared to early CAG without PCI (65.6% versus
      45.5%, OR 2.29 [95% CI 1.41-3.69]; p<0.001). After multivariate adjustment and
      propensity matching, early PCI remained significantly associated with improved
      survival compared with early CAG without PCI and no early CAG, but early CAG
      without PCI was no longer significantly associated with improved outcome compared
      with no early CAG. Early CAG and early PCI were not associated with an increase
      in transfusions or acute kidney injury. CONCLUSIONS: Early CAG and PCI are
      associated with improved survival and functional outcomes after OHCA, but only
      early PCI was associated with a significant benefit after statistical adjustment.
      Our analysis supports the performance of immediate CAG to determine the need for
      PCI in selected patients following resuscitation from OHCA.

PMID- 29223602
TI  - Prognostic significance of shockable and non-shockable cardiac arrest in ST
      segment elevation myocardial infarction patients undergoing primary angioplasty.
AB  - OBJECTIVE: To determine, in patients with ST-segment Elevation Myocardial
      Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI),
      the prognostic weight of cardiac arrest (CA) according to the type of rhythm
      (shockable vs. non-shockable). METHODS: We prospectively enrolled 3278
      consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used
      to establish the relation to 1-year cardiac mortality of both type of CA. In
      patients suffering from CA we identified predictors of both poor neurological
      outcome (cerebral performance categories 3-5) and cardiac mortality at 1year.
      RESULTS: The incidence of CA was 7.26% (n=238). Of these, 196 (5.98%) had an
      initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year
      follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm
      (adjusted-HR=1.61; 95%CI 1.08-2.43, p=0.02) and non-shockable rhythm (adjusted
      HR=3.83; 95%CI 2.36-6.22, p<0.001) were independently associated with 1-year
      cardiac mortality. Among patients with CA those with shockable rhythm had a lower
      risk of poor neurological outcome at 1year follow up (adjusted OR=0.22: 95%CI;
      0.08-0.55, p=0.001). Independent predictors of 1-y cardiac mortality were: non
      shockable rhythm (adjusted HR=2.6; 95%CI; 1.48-4.5, p=0.001), crew-witnessed CA,
      diabetes mellitus, left ventricle ejection fraction and creatinine on admission.
      There was a significant interaction between type of rhythm and crew-witnessed CA
      (p=0.026). CONCLUSIONS: In patients with STEMI undergoing PPCI patients with both
      shockable and non shockable CA are at increased risk of 1-year cardiac mortality.
      Among patients with CA those with non shockable rhythm have an higher risk of
      both poor neurological outcome and cardiac mortality at 1year.

PMID- 29223603
TI  - Factors predicting quality of life and societal participation after survival of a
      cardiac arrest: A prognostic longitudinal cohort study.
AB  - AIM: For those patients who suffer unfavourable outcome after survival of cardiac
      arrest, it is important to know whether this can be predicted at an early stage.
      Support can subsequently be provided. This study aimed to identify early
      prognostic factors of quality of life (QOL) and societal participation at one
      year post-cardiac arrest. METHODS: The design was a prospective longitudinal
      cohort study following cardiac arrest survivors up to one year. Prognostic
      personal, injury-related, function-related and subjective outcome factors were
      selected and entered into a hierarchical regression model to assess whether they
      were predictive of QOL and societal participation at one year post-cardiac
      arrest. RESULTS: Hundred and ten cardiac arrest survivors were included. Not
      having a partner, more functional limitations (at two weeks) and cognitive
      complaints were significantly predictive of lower physical QOL, while higher
      levels of anxiety and depression symptoms (at three months) were significant
      predictors of mental QOL. A neurological history and higher levels of anxiety and
      depression symptoms were significantly predictive of lower brain injury-specific
      QOL. Societal participation was only predicted by premorbid functioning.
      CONCLUSION: This study identified prognostic factors of QOL and societal
      participation one year after survival of cardiac arrest. Screening of these
      factors in early stages can identify those survivors with possibly unfavourable
      QOL at one year post cardiac arrest. For those survivors, preventive and targeted
      interventions may be offered.

PMID- 29223604
TI  - Robot-assisted Retrohepatic Inferior Vena Cava Thrombectomy: First or Second
      Porta Hepatis as an Important Boundary Landmark.
AB  - BACKGROUND: Robot-assisted retrohepatic inferior vena cava (IVC) thrombectomy (RA
      R-IVCTE) has been reported only for limited series. OBJECTIVE: To describe in
      detail the techniques for RA-R-IVCTE with regard to the relationship of a
      proximal thrombus to either the first porta hepatis (FPH) or second porta hepatis
      (SPH). DESIGN, SETTING, AND PARTICIPANTS: From May 2013 to July 2016, 22 patients
      with R-IVC tumor thrombi were admitted to our hospital. SURGICAL PROCEDURE: RA-R
      IVCTE was performed using the Rummel tourniquet technique. For a proximal
      thrombus inferior to the FPH, we ligated some short hepatic veins (SHVs;
      typically 1-3). For a thrombus between the FPH and SPH, we mobilized the right
      lobe of the liver from the IVC by ligating additional SHVs. For a thrombus near
      or above the SPH but below the diaphragm, we mobilized both the right and left
      lobes of the liver to obtain high proximal control of the suprahepatic and
      infradiaphragmatic IVC, and simultaneously clamped the FPH. MEASUREMENTS:
      Detailed techniques were described for various scenarios and perioperative
      outcomes were recorded. RESULTS AND LIMITATIONS: The median operation time was
      285min (interquartile range [IQR] 191-390). Intraoperative estimated blood loss
      was 1350ml (IQR 1000-2075ml). Some 63.6% of patients required an intraoperative
      blood transfusion and 68% were transferred to the intensive care unit after
      surgery. Grade IV complications developed in five cases. Vascular injuries (4
      cases) were treated with intraoperative endoscopic sutures. An intestinal fistula
      was found on postoperative day 7 in one case; treatment with gastrointestinal
      decompression and drainage resolved the condition by 1 mo. CONCLUSIONS: Even
      though the risks involved are high, RA-R-IVCTE is feasible for selected patients.
      The FPH/SPH is an important boundary landmark for RA-R-IVCTE. The location of
      proximal IVC tumor thrombi in relation to the FPH or SPH should determine the
      technique used. PATIENT SUMMARY: Robot-assisted thrombectomy for retrohepatic
      inferior vena cava tumor thrombus is feasible in selected patients.

PMID- 29223605
TI  - Updated European Association of Urology Guidelines Recommendations for the
      Treatment of First-line Metastatic Clear Cell Renal Cancer.
AB  - : The randomised phase III clinical trial Checkmate-214 showed a survival
      superiority for the combination of ipilimumab and nivolumab when compared with
      the previous standard of care in first-line metastatic/advanced clear cell renal
      cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214:
      efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naive
      advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1
      expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline
      standard of care for this disease and have implications for the selection of
      subsequent therapies. For this reason the European Association of Urology RCC
      guidelines have been updated. PATIENT SUMMARY: The European Association of
      Urology guidelines will be updated based on the results of the phase III
      Checkmate-214 clinical trial. The trial showed superior survival for a
      combination of ipilimumab and nivolumab (IN), compared with the previous standard
      of care, in intermediate- and poor-risk patients with metastatic clear cell renal
      cell carcinoma. When IN is not safe or feasible, alternative agents such as
      sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at
      present, the data from the trial are immature in favourable-risk patients.
      Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of
      patients.

PMID- 29223606
TI  - Re: Availability of Evidence of Benefits on Overall Survival and Quality of Life
      of Cancer Drugs Approved by European Medicines Agency: Retrospective Cohort Study
      of Drug Approvals 2009-2013.

PMID- 29223607
TI  - Re: Positive Surgical Margins and Local Recurrence After Simple Enucleation and
      Standard Partial Nephrectomy for Malignant Renal Tumors: Systematic Review of the
      Literature and Meta-analysis of Prevalence.

PMID- 29223608
TI  - Gastrointestinal colonisation with three different NDM-1-producing
      enterobacterial species isolated from an inpatient in Tehran, Iran.

PMID- 29223609
TI  - [Recurrent postpartum pyoderma gangrenosum and fatal cardiomyopathy].
AB  - BACKGROUND: We report a case of recurrent post-partum pyoderma gangrenosum (PG)
      complicated by post-partum cardiomyopathy (PPCM). PATIENTS AND METHODS: A 23-year
      old woman presented with a previous medical history of aseptic abscess of the
      left breast in her fourth pregnancy, which developed after surgical drainage of
      an inflammatory ulceration treated by atraumatic topical care. During her fifth
      pregnancy, the patient presented a large and painful ulceration in relation to
      the scar of the Caesarean section, despite the introduction of broad-spectrum
      antibiotic therapy. Bacteriological samples were negative. Histological
      examination militated in favor of PG. One week after initiation of corticosteroid
      therapy, the patient suddenly showed signs of heart failure. Based on trans
      thoracic echocardiography PPCM was diagnosed, and the outcome was fatal.
      DISCUSSION: This observation raises the question of the relationship between PG
      and pregnancy and describes the association of PG and PPCM. PG occurs rarely
      during pregnancy and it may be induced by the rise in G-CSF levels found in
      pregnant women. The association with PPCM seen in our patient could have been due
      to the development of an anti-angiogenic climate at the end of pregnancy,
      together with inflammatory myocardial aggression linked to the PG.

PMID- 29223610
TI  - [Attractiveness of a university hospital career in France: Analysis of
      perceptions among young dermatologists in 2016].

PMID- 29223611
TI  - Individuals exhibit consistent differences in their metabolic rates across
      changing thermal conditions.
AB  - Metabolic rate has been linked to growth, reproduction, and survival at the
      individual level and is thought to have far reaching consequences for the ecology
      and evolution of organisms. However, metabolic rates must be consistent (i.e.
      repeatable) over at least some portion of the lifetime in order to predict their
      longer-term effects on population dynamics and how they will respond to
      selection. Previous studies demonstrate that metabolic rates are repeatable under
      constant conditions but potentially less so in more variable environments. We
      measured the standard (=minimum) metabolic rate, maximum metabolic rate, and
      aerobic scope (=interval between standard and maximum rates) in juvenile brown
      trout (Salmo trutta) after 5weeks acclimation to each of three consecutive test
      temperatures (10, 13, and then 16 degrees C) that simulated the warming
      conditions experienced throughout their first summer of growth. We found that
      metabolic rates are repeatable over a period of months under changing thermal
      conditions: individual trout exhibited consistent differences in all three
      metabolic traits across increasing temperatures. Initial among-individual
      differences in metabolism are thus likely to have significant consequences for
      fitness-related traits over key periods of their life history.

PMID- 29223612
TI  - Predictive value of focused assessment with sonography for trauma (FAST) for
      laparotomy in unstable polytrauma Egyptians patients.
AB  - PURPOSE: The emergency physicians face significant clinical uncertainty when
      multiple trauma patients arrive in the emergency department (ED). The priorities
      for assessment and treatment of polytrauma patients are established in the
      primary survey. Focused assessment with sonography for trauma (FAST) is very
      essential clinical skill during trauma resuscitation. Use of point of care
      ultrasound among the trauma team working in the primary survey in emergency care
      settings is lacking in Suez Canal University Hospitals even ultrasound machine
      not available in ED. This study aims to evaluate the accuracy of FAST in
      hemodynamically unstable polytraumatized patients and to determine its role as an
      indication of laparotomy. METHODS: This study is a cross-sectional study included
      150 polytrauma patients with a blunt mechanism admitted in Suez Canal University
      Hospital. Firstly primary survey by airway check, cervical spine securing with
      neck collar, maintenance of breathing/circulation and management of life
      threading conditions if present were conducted accordingly to ATLS (advanced
      trauma life support) guidelines. The patients were assessed in the primary survey
      using the FAST as a tool to determine the presence of intra-abdominal collection.
      RESULTS: A total of 150 patients, and FAST scans were performed in all cases. The
      sensitivity and specificity were 92.6% and 100%, respectively. The negative
      predictive value was 92%, while the positive predictive value of FAST was 100%.
      The accuracy of FAST was 96%. CONCLUSION: FAST is an important method to detect
      intra-abdominal fluid in the initial assessment in hemodynamically unstable
      polytrauma patients with high accuracy.

PMID- 29223613
TI  - 18F-NaF PET/CT for the evaluation of temporomandibular joint disorder.
AB  - AIM: To investigate the usefulness of a quantitative parameter (maximum
      standardised uptake value [SUVmax]) of 18F-sodium fluoride (NaF) positron
      emission tomography (PET)/computed tomography (CT) for the evaluation of
      temporomandibular joint (TMJ) disorder (TMD). MATERIALS AND METHODS: Seventy-six
      TMD patients (male: female=14:62, age=40.3+/-17.1 years, bilateral:
      unilateral=40:36) with 152 TMJs were enrolled. The 18F-NaF PET/CT parameter
      (SUVmax) was compared with the presence of TMJ arthralgia (arthralgic=86, non
      arthralgic=66) and clinical subtypes based on the Research Diagnostic Criteria
      for TMD Axis I (TMD osteoarthritis=49, non-TMD osteoarthritis=67, and
      asymptomatic TMJ=36). Splint therapy was applied to 48 patients for 6 months
      without considering 18F-NaF PET/CT findings. Post-splint therapy 18F-NaF PET/CT
      was performed in 32 patients and clinical responses to the therapy were
      classified into improvement (n=33), no change (n=10), or aggravation (n=7) for 50
      TMJs excluding asymptomatic TMJs (n=14). RESULTS: SUVmax was significantly
      greater in arthralgic TMJs than in non-arthralgic TMJs (6.62+/-3.56 versus 4.32+/
      1.53, p<0.0001). SUVmax was also significantly greater in TMD osteoarthritis
      (6.75+/-3.85) than in non-TMD osteoarthritis (5.21+/-2.70) and asymptomatic TMJs
      (4.86+/-1.99; p=0.0386). After splint therapy, SUVmax was significantly increased
      in aggravated TMJs (from 7.80+/-3.72 to 11.00+/-5.74, p=0.0156), whereas no
      significant change in SUVmax was observed in improved (from 6.16+/-2.68 to 6.09+/
      2.60, p=0.4915) and unchanged (from 6.46+/-4.19 to 6.77+/-4.32, p=0.3223) TMJs.
      CONCLUSIONS: 18F-NaF PET/CT is a useful imaging tool for TMD evaluation because
      SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD
      osteoarthritis, and a correlation with the therapeutic response.

PMID- 29223614
TI  - Host susceptibility to MERS-CoV infection, a retrospective cohort study of the
      2015 Korean MERS outbreak.
AB  - To evaluate host susceptibility factors to Middle East respiratory syndrome
      coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from
      the single largest exposure event of the 2015 Korean MERS outbreak. A total of
      175 patients were closely exposed to a super-spreader, 26 of which were infected
      (14.9%). In a multivariate analysis, history of autologous stem cell
      transplantation (HR, 31.151; 95% CI, 5.447-178.145; P < 0.001) and tachypnea at
      ED (HR, 4.392; 95% CI, 1.402-13.761; P = 0.011) were significantly associated
      with MERS-CoV infection.

PMID- 29223615
TI  - Differences in drug susceptibility pattern between Mycobacterium avium and
      Mycobacterium intracellulare isolated in respiratory specimens.
AB  - Mycobacterium avium complex (MAC) is the most common etiologic organisms of
      nontuberculous mycobacteria (NTM) lung disease. In this study, we aimed to
      retrospectively investigate the differences in drug susceptibility patterns of
      two major MAC species; Mycobacterium avium and Mycobacterium intracellulare. A
      total of 1883 major two MAC isolates (1060 M. avium and 823 M. intracellulare)
      from respiratory specimens were included in this study during the period
      2011?2016. The minimum inhibitory concentrations (MICs) were determined by broth
      microdilution method and MIC50/MIC90 values were derived from MIC distribution.
      M. intracellulare had generally low susceptible rates than M. avium for almost
      all tested antimicrobials except ethambutol and amikacin. The susceptible rate to
      clarithromycin was >94% of the MAC without significant differences between the
      two species. The MIC50 values of ciprofloxacin, clarithromycin, linezolid,
      moxifloxacin, and rifampicin were higher in M. intracellulare than in M. avium,
      contrary to the results of ethambutol with a higher MIC50 in M. avium. In
      general, M. intracellulare showed a higher resistance rate and higher MIC50
      values than M. avium. Differences between this study and previous reports suggest
      regional differences in drug susceptibility profile of MAC species.

PMID- 29223617
TI  - Silicone lip implant for augmentation in cleft lip.

PMID- 29223616
TI  - Three new highly oxygenated sterols and one new dihydroisocoumarin from the
      marine sponge-derived fungus Cladosporium sp. SCSIO41007.
AB  - Three new highly oxygenated sterols (1-3) and a new dihydroisocoumarin (7)
      together with six known compounds were isolated from the extracts of the culture
      of a sponge-derived fungus Cladosporium sp. SCSIO41007. The structures of all new
      compounds (1-3, 7) were determined by the extensive spectroscopic analysis
      including NMR, MS, IR, and UV. Their absolute configurations were determined by X
      ray single-crystal and CD data analysis. Compound 2 exhibited weak inhibitory
      activity against H3N2 with the IC50 value of 16.2 MUM.

PMID- 29223618
TI  - Post-operative care of VRAM flaps for perineal reconstruction.

PMID- 29223621
TI  - Does observation of a disabled child's action moderate action execution?
      Implication for the use of Action Observation Therapy for patient rehabilitation.
AB  - BACKGROUND: Research investigating action observation-execution priming has
      mainly manipulated congruent versus incongruent action, and aspects of action
      expertise/capability. More specifically, the literature suggests enhanced
      performance priming following action observation by actors closely matched to
      participant expertise. The aim of the present study was to extend the
      understanding of action expertise effects by investigating action priming in
      healthy participants after observing a mild hemiparetic child actor versus a
      neurologically healthy child actor. METHODS: 16 healthy right-handed children,
      aged 6-13 years were tested. Several motor assessments were performed, including
      gross and fine manual motor ability, and upper limb kinematics measured using a
      precise robotic device. A cross-over design consisted in two experimental
      conditions (observing actions performed by a child with hemiparesis versus
      observing actions performed by a healthy child) and a pre-observation double
      baseline control condition, with the data analyzed using repeated measures ANOVA.
      RESULTS: Relative to baseline, both types of action observation conditions
      enhanced fine manual dexterity, but observing the hemiparetic child enhanced
      gross manual dexterity and upper limb velocity kinematics relative to observing
      actions performed by a healthy child. No effects were shown on measures of
      smoothness and accuracy. DISCUSSION: Contradictorily to hypotheses discussed in
      the literature, results here showed evidence of enhanced action execution when
      healthy children observed hemiparetic compared to healthy child actions. These
      results are discussed in terms of how patient compared to healthy actors may be
      useful for clinical action observation priming therapy.

PMID- 29223619
TI  - Differential effects of hepatic cirrhosis on the intrinsic clearances of
      sorafenib and imatinib by CYPs in human liver.
AB  - The tyrosine kinase inhibitors sorafenib and imatinib are important in the
      treatment of a range of cancers but adverse effects in some patients necessitate
      dosage modifications. CYP3A4 has a major role in the oxidation of sorafenib to
      its N-oxide and N-hydroxymethyl metabolites and also acts in concert with CYP2C8
      to mediate imatinib N-demethylation. CYP3A4 expression and function are impaired
      in patients with advanced liver disease, whereas the functions of CYP2C enzymes
      are relatively preserved. We evaluated the biotransformation of sorafenib and
      imatinib in well-characterized microsomal fractions from 17 control subjects and
      19 individuals with hepatic cirrhosis of varying severity. The principal findings
      were that liver disease impaired the microsomal oxidation of sorafenib to its
      major metabolites to 40-44% of control (P<0.01), whereas the N-demethylation of
      imatinib was relatively unimpaired. The impairments in sorafenib
      biotransformation were correlated with decreased serum albumin concentrations and
      increased serum bilirubin concentrations in patients with liver disease, but not
      with the overall grade of liver disease according to the Child-Pugh system. In
      contrast, there was no relationship between imatinib N-demethylation and
      clinicopathologic factors in liver disease patients. These findings were
      accounted for in terms of the differential roles of CYPs 3A4 and 2C8 in the
      intrinsic clearance of the drugs. CYP3A4 has the major role in the intrinsic
      clearance of sorafenib but plays a secondary role to CYP2C8 in the intrinsic
      clearance of imatinib. In agreement with these findings CYP2C protein expression
      and CYP2C8-mediated paclitaxel 6alpha-hydroxylation were unimpaired in cirrhotic
      livers. This information could be adapted in individualized approaches such as in
      vivo CYP3A4 phenotyping to optimize sorafenib safety and efficacy in cancer
      patients with liver dysfunction.

PMID- 29223620
TI  - Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis,
      and Survival Among Incident Peritoneal Dialysis Patients.
AB  - BACKGROUND: The prevalence of severe obesity, often considered a contraindication
      to peritoneal dialysis (PD), has increased over time. However, mortality has
      decreased more rapidly in the PD population than the hemodialysis (HD) population
      in the United States. The association between obesity and clinical outcomes among
      patients with end-stage kidney disease remains unclear in the current era. STUDY
      DESIGN: Historical cohort study. SETTING & PARTICIPANTS: 15,573 incident PD
      patients from a large US dialysis organization (2007-2011). PREDICTOR: Body mass
      index (BMI). OUTCOMES: Modality longevity, residual renal creatinine clearance,
      peritonitis, and survival. RESULTS: Higher BMI was significantly associated with
      shorter time to transfer to HD therapy (P for trend < 0.001), longer time to
      kidney transplantation (P for trend < 0.001), and, with borderline significance,
      more frequent peritonitis-related hospitalization (P for trend = 0.05). Compared
      with lean patients, obese patients had faster declines in residual kidney
      function (P for trend < 0.001) and consistently achieved lower total Kt/V over
      time (P for trend < 0.001) despite greater increases in dialysis Kt/V (P for
      trend < 0.001). There was a U-shaped association between BMI and mortality, with
      the greatest survival associated with the BMI range of 30 to < 35kg/m2 in the
      case-mix adjusted model. Compared with matched HD patients, PD patients had lower
      mortality in the BMI categories of < 25 and 25 to < 35kg/m2 and had equivalent
      survival in the BMI category >= 35kg/m2 (P for interaction = 0.001 [vs < 25
      kg/m2]). This attenuation in survival difference among patients with severe
      obesity was observed only in patients with diabetes, but not those without
      diabetes. LIMITATIONS: Inability to evaluate causal associations. Potential
      indication bias. CONCLUSIONS: Whereas obese PD patients had higher risk for
      complications than nonobese PD patients, their survival was no worse than matched
      HD patients.

PMID- 29223622
TI  - Airway changes following labor and delivery in preeclamptic parturients: a
      prospective case control study.
AB  - BACKGROUND: Preeclampsia is associated with greater narrowing of the airway than
      normal pregnancy, but it is not known if these changes worsen during labor and
      delivery. The aim of the study was to evaluate the airway during and after labor
      in women with or without preeclampsia. METHODS: Twenty-five normal and 25
      severely preeclamptic pregnant women in early labor were recruited in this single
      center, prospective, case-control study. Airway assessment was performed (a)
      before active labor (b) within one hour of delivery and (c) 24-48 h postpartum.
      The Mallampati grade was the primary outcome. Sonographic measurements of tongue
      thickness, anterior neck soft tissue at the level of the hyoid bone and the vocal
      cords, thyromental distance, and neck circumference, were secondary outcomes.
      RESULTS: The Mallampati score increased from the pre-labor to the post-labor
      period in both preeclamptic and normotensive patients (P=0.001 and P=0.002
      respectively). A significant difference in tissue thickness at the hyoid level
      was observed between preeclamptic and normotensive patients pre-labor (P=0.035),
      post-labor (P=0.05) and postpartum (P=0.05). There was no significant difference
      in thyromental distance or neck circumference between groups at any time. The
      total duration of labor and a Mallampati change by one grade correlated (Spearman
      correlation coefficient 0.473). CONCLUSION: Airway sonography may provide useful
      bedside anatomical information for prediction of difficult laryngoscopy. The
      change in airway dimensions and the Mallampati score during labor may persist for
      48 h postpartum in both groups. Those with prolonged labor are more susceptible
      to changes in airway dimensions.

PMID- 29223623
TI  - Gene-Indexed Mutations in Maize.
AB  - The availability of the B73 inbred reference genome sets the stage for high
      throughput functional characterization of maize genes on a whole-genome scale.
      Among the 39 324 protein-coding genes predicted, the vast majority are untapped
      due to the lack of suitable high-throughput reverse genetic resources. We have
      generated a gene-indexed maize mutant collection through ethyl methanesulfonate
      mutagenesis and detected the mutations by combining exome capture and next
      generation sequencing. A total of 1086 mutated M1 plants were sequenced, and 195
      268 CG>TA-type point mutations, including stop gain/loss, missplice, start
      gain/loss, and various non-synonymous protein mutations as well as 4610 InDel
      mutations, were identified. These mutations were distributed on 32 069 genes,
      representing 82% of the predicted protein-coding genes in the maize genome. We
      detected an average of 180 mutations per mutant line and 6.1 mutations per gene.
      As many as 27 214 mutations of start codons, stop codons, or missplice sites were
      identified in 14 101 genes, among which 6232 individual genes harbored more than
      two such mutations. Application of this mutant collection is exemplified by the
      identification of the ent-kaurene synthase gene, which encodes a key enzyme in
      the gibberellin biosynthesis pathway. This gene-indexed genome-wide mutation
      collection provides an important resource for functional analysis of maize genes
      and may bring desirable allelic variants for genetic breeding in maize.

PMID- 29223624
TI  - Implementation of the Alarm Distress Baby Scale as a universal screening
      instrument in primary care: feasibility, acceptability, and predictors of
      professionals' adherence to guidelines.
AB  - BACKGROUND: Infant socioemotional development is often held under informal
      surveillance, but a formal screening program is needed to ensure systematic
      identification of developmental risk. Even when screening programs exist, they
      are often ineffective because health care professionals do not adhere to
      screening guidelines, resulting in low screening prevalence rates. OBJECTIVES: To
      examine feasibility and acceptability of implementing universal screening for
      infant socioemotional problems with the Alarm Distress Baby Scale in primary
      care. The following questions were addressed: Is it possible to obtain acceptable
      screening prevalence rates within a 1-year period? How do the primary care
      workers (in this case, health visitors) experience using the instrument? Are
      attitudes toward using the instrument related to screening prevalence rates?
      DESIGN: A longitudinal mixed-method study (surveys, data from the health
      visitors' digital filing system, and qualitative coding of answers to open-ended
      questions) was undertaken. SETTING AND PARTICIPANTS: Health visitors in three of
      five districts of the City of Copenhagen, Denmark (N=79). METHODS: We describe
      and evaluate the implementation process from the date the health visitors started
      the training on how to use the Alarm Distress Baby Scale to one year after they
      began using the instrument in practice. To monitor screening prevalence rates and
      adherence to guidelines, we used three data extractions (6, 9, and 12 months post
      implementation) from the electronic filing system. Surveys including both
      quantitative and open-ended questions (pre- and post-implementation) were used to
      examine experiences with and attitudes towards the instrument. Descriptive and
      inferential statistical and qualitative content analyses were used. RESULTS:
      Screening prevalence rates increased during the first year: Six months after
      implementation 47% (n=405) of the children had been screened; 12 months after
      implementation 79% (n=789) of the children were screened (the same child was not
      counted more than once). Most (92%) of the health visitors reported that the
      instrument made a positive contribution to their work. The majority (81%) also
      reported that it posed a challenge in their daily work at least to some degree.
      The health visitors' attitudes (positive and negative) toward the Alarm Distress
      Baby Scale, measured 7 months post-implementation, significantly predicted
      screening prevalence rates 12 months post-implementation. CONCLUSIONS: Adding the
      Alarm Distress Baby Scale to an established surveillance program is feasible and
      accepTable Screening prevalence rates may be related to the primary care worker's
      attitude toward the instrument, i.e. successful implementation relies on an
      instrument that adds value to the work of the screener.

PMID- 29223626
TI  - Sleep and quality of life of patients with glycogen storage disease on standard
      and modified uncooked cornstarch.
AB  - BACKGROUND: Glycemic control in hepatic glycogen storage diseases (GSDs) relies
      on specific nutritional recommendations, including strict avoidance of a fasting
      period. Uncooked cornstarch (UCCS) is an important therapeutic component. A new
      modified UCCS, GlycosadeTM, was created with the objective of prolonging
      euglycemia. We aimed to determine the length of euglycemia on GlycosadeTM using a
      continuous glucose monitor (CGM) and to evaluate whether longer euglycemia and
      thus less nighttime interruptions would improve sleep and quality of life (QoL)
      after the introduction of the modified cornstarch. METHODS: We conducted a
      prospective cohort study to assess quality and quantity of sleep and quality of
      life (QoL) in patients with GSDs on standard UCCS and after the introduction of
      GlycosadeTM. Sleep and QoL evaluation was done for patients using validated
      questionnaires, a standardized sleep diary and actigraphy. Length of fast and
      glucose variability were determined with CGM. RESULTS: Nine adults with GSD Ia
      took part in the study. GlycosadeTM introduction was done under close supervision
      during a hospital admission. Comparison of sleep in 9 patients showed sleep
      disturbances on standard UCCS that were improved with GlycosadeTM. QoL was normal
      both pre and post GlycosadeTM. The CGM confirmed maintenance of a longer fasting
      period with GlycosadeTM at home. CONCLUSION: GlycosadeTM represents an
      alternative option for GSD patients. We showed possible benefits in terms of
      sleep quality. We also confirmed the longer length of fast on GlycosadeTM.
      SYNOPSIS: A new modified form of uncooked starch for patients with glycogen
      storage disease represents an alternative option as it showed a longer length of
      fast and improvements in sleep quality.

PMID- 29223625
TI  - Development and validation of a predictive model for excessive postpartum blood
      loss: A retrospective, cohort study.
AB  - BACKGROUND: postpartum haemorrhage is one of the leading causes of maternal
      morbidity and mortality worldwide. Despite the use of uterotonics agents as
      preventive measure, it remains a challenge to identify those women who are at
      increased risk of postpartum bleeding. OBJECTIVE: to develop and to validate a
      predictive model to assess the risk of excessive bleeding in women with vaginal
      birth. DESIGN: retrospective cohorts study. SETTING: "Mancha-Centro Hospital"
      (Spain). PARTICIPANTS: the elaboration of the predictive model was based on a
      derivation cohort consisting of 2336 women between 2009 and 2011. For validation
      purposes, a prospective cohort of 953 women between 2013 and 2014 were employed.
      Women with antenatal fetal demise, multiple pregnancies and gestations under 35
      weeks were excluded METHODS: we used a multivariate analysis with binary logistic
      regression, Ridge Regression and areas under the Receiver Operating
      Characteristic curves to determine the predictive ability of the proposed model.
      RESULTS: there was 197 (8.43%) women with excessive bleeding in the derivation
      cohort and 63 (6.61%) women in the validation cohort. Predictive factors in the
      final model were: maternal age, primiparity, duration of the first and second
      stages of labour, neonatal birth weight and antepartum haemoglobin levels.
      Accordingly, the predictive ability of this model in the derivation cohort was
      0.90 (95% CI: 0.85-0.93), while it remained 0.83 (95% CI: 0.74-0.92) in the
      validation cohort. CONCLUSIONS: this predictive model is proved to have an
      excellent predictive ability in the derivation cohort, and its validation in a
      latter population equally shows a good ability for prediction. This model can be
      employed to identify women with a higher risk of postpartum haemorrhage.

PMID- 29223628
TI  - Five- and 10-Year Follow-Up of Nonvascularized Toe Phalanx Transfers.
AB  - PURPOSE: The purpose of this study was to evaluate long-term outcomes of
      nonvascularized toe phalanx transfer. METHODS: We retrospectively reviewed 54
      nonvascularized toe phalanx transfers in 29 children with symbrachydactyly. Forty
      seven transfers in 24 children were evaluated at 5-year follow-up and 27
      transfers in 14 children were evaluated at 10-year follow-up. We recorded the
      incidence of the early physeal closure and the length of the transferred toe
      phalanx on plain radiographs at 5- and 10-year follow-up. Growth rate in the
      first 5 years and the following 5 years were calculated. Function of the
      metacarpophalangeal joint (motion, stability, and alignment) was also evaluated.
      RESULTS: The mean age at surgery was 1.5 years. Seven toe phalanges were trimmed
      because the skin pocket was tight. Five transfers required revision surgery for
      partial necrosis of the skin pocket. At 5-year follow-up, the physis was closed
      in 23%, and at 10 years, 78% of physes were closed. The phalanx length was 87% of
      expected at 5-year follow-up and 71% at 10-year follow-up. Growth rate was 0.83
      mm/y in the first 5 years and 0.22 mm/y in the following 5 years. Active motion
      was rated as good in 24, fair in 7, and poor in 16. Stability and alignment were
      rated as good in 37 and 33, fair in 8 and 5, and poor in 2 and 9, respectively.
      CONCLUSIONS: Nonvascularized toe phalanx transfer offered a relatively simple
      method to lengthen short digits and to provide satisfactory function. The
      transferred toe phalanges grew at a near-normal rate in the first 5 years, but
      the growth rate decreased between 5 and 10 years. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 29223629
TI  - A New Clinical Sign of Lumbrical Plus Finger.
AB  - Paradoxical finger extension is the classical clinical presentation of the
      lumbrical plus syndrome. We report a new additional sign, increased
      metacarpophalangeal flexion of the involved finger when the patient tries to make
      a fist. Three cases of lumbrical tightness are discussed, illustrating this new
      sign in 3 different clinical settings. The new sign was present in all 3 cases.
      Lumbrical tenotomy corrected the paradoxical interphalangeal extension and partly
      the increased metacarpophalangeal flexion. The lumbrical tendon has a relatively
      high moment arm relative to the metacarpophalangeal joint, which could explain
      the basis of this clinical sign. This new physical examination sign may help in
      diagnosing the lumbrical plus syndrome, a subtle complication of flexor digitorum
      profundus lesions that is not easily diagnosed but which is easily addressed.

PMID- 29223630
TI  - Postoperative Loss of Midline Function in Brachial Plexus Birth Palsy.
AB  - PURPOSE: To identify the rate of and predictive variables for functionally
      limited shoulder internal rotation in postoperative patients with brachial plexus
      birth palsy. METHODS: Records of patients with brachial plexus birth palsy who
      had surgery on the affected upper extremity during a 10-year period were
      retrospectively reviewed. Patient demographics, physical examinations, and all
      upper extremity procedures were recorded. Loss of midline function (LOM) was
      defined as a Modified Mallet Scale or Active Movement Scale (AMS) internal
      rotation score <3. Exclusion criteria were <1-year follow-up after the most
      recent procedure, insufficient documentation, or preexisting LOM. Multivariable
      logistic regression was performed on 3 different scenarios of candidate variables
      to identify those associated with LOM. All scenarios included each procedure as a
      candidate variable. Scenario A additionally analyzed preprocedural AMS scores.
      Scenario B additionally analyzed preprocedural Modified Mallet Scale scores.
      Scenario C isolated the surgical pathway without preprocedural examination
      scores. RESULTS: Among 172 included patients, 34 (19.8%) developed LOM.
      Predictive variables associated with LOM included severity of initial palsy (C5
      7, odds ratio 3.6; C5-T1, odds ratio 4.9), poor recovery of upper trunk motor
      function before the patient's first surgery (specifically Modified Mallet Scale
      abduction < 4, AMS elbow flexion < 3, and AMS wrist extension < 3), and patients
      who ultimately required surgical glenohumeral reduction (odds ratio 3.6). Age,
      number of procedures, closed shoulder reduction with casting, shoulder tendon
      transfers, and external rotation humeral osteotomies were not predictive of LOM.
      CONCLUSIONS: Approximately 1 in every 5 patients with brachial plexus birth palsy
      will develop LOM after entering a surgical algorithm designed to improve shoulder
      external rotation. Patients with a more severe initial palsy (C5-7 or global),
      poor spontaneous recovery of upper trunk motor function (elbow flexion or wrist
      extension) before their first procedure, and those who ultimately require
      surgical glenohumeral joint reduction should be counseled as having a higher odds
      of LOM development. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 29223631
TI  - Nontuberculous Mycobacterial Infections of the Upper Extremity: 15-Year
      Experience at a Tertiary Care Medical Center.
AB  - PURPOSE: To present our experience with culture-positive, nontuberculous
      mycobacterial infections (NTMI) of the upper extremity and to compare the
      clinical features and outcomes of treatment among immunocompetent and
      immunocompromised patients. METHODS: All patients at our medical center diagnosed
      with NTMI of the upper extremity from December 1, 2000, through December 31,
      2015, were included. We performed a retrospective analysis of patient demographic
      characteristics, delay to diagnosis, risk factors, clinical presentation,
      specific location, diagnostic testing, treatment regimens, and outcomes. These
      variables were compared between immunocompetent and immunocompromised patients.
      RESULTS: Forty-four patients were identified with culture-positive NTMI of the
      upper extremity. Of the patients, 27 (61%) were men (median age, 59 years [range,
      23-83 years]). Twenty (45%) patients were immunocompromised. Immunocompromised
      patients had fewer known inoculation injuries compared with immunocompetent
      patients (45% vs 92%). A significant difference existed in the treatment regimens
      selected for immunocompetent versus immunocompromised patients: immunocompetent
      patients were more often treated with both antibiotics and surgery (88% vs 50%),
      whereas immunocompromised patients were more often treated with antibiotics alone
      (45% vs 4%). Overall, 24% experienced treatment failure and 9% died. Outcomes
      were relatively similar between immunocompetent and immunocompromised patients. A
      shorter delay to diagnosis was associated with a lower failure rate. CONCLUSIONS:
      Diagnosis of upper-extremity NTMI is often delayed because of indolent
      presentation and lack of clinical suspicion. The clinical presentation,
      diagnostic delay, and diagnostic testing results are similar between
      immunocompetent and immunocompromised patients. Although treatment varied
      significantly between patient groups, outcomes were similar. Timely diagnosis has
      the greatest impact on patient outcome. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 29223632
TI  - Comparative Morbidity of Cubital Tunnel Surgeries: A Prospective Cohort Study.
AB  - PURPOSE: Randomized controlled trials have not identified a superior surgical
      approach to cubital tunnel syndrome surgery. This study evaluates the early
      morbidity of open in situ decompression and transposition. METHODS: This
      prospective cohort study enrolled 125 adult patients indicated for cubital tunnel
      surgery at a tertiary institution. Exclusion criteria included preoperative use
      of narcotics and concurrent elbow procedures. In situ decompressions (n = 47) and
      ulnar nerve transpositions (n = 78) were performed. Data were collected by
      independent clinicians at 3 postoperative intervals: 1 to 3 weeks, 4 to 8 weeks,
      and longer than 8 weeks. Postoperative data quantified surgical morbidity: visual
      analog scale (0-10) surgical site pain, narcotic consumption, patient-reported
      disability (Levine-Katz, Patient-Reported Elbow Evaluation [PREE] scores).
      Olecranon paresthesia and wound complications (hematoma, drainage, infection)
      were recorded. RESULTS: No preoperative differences in age, sex, or the presence
      of pain existed between the surgical groups. Surgical site pain was not
      significantly different at any time. Following transposition, a significantly
      greater percentage of patients were using narcotics at 4 to 8 weeks after surgery
      and the average total morphine equivalents consumed per patient was significantly
      greater. Both Levine-Katz and PREE scores indicated greater disability at 1 to 3
      and 4 to 8 weeks after transposition, but this significant difference resolved by
      final follow-up. Olecranon paresthesias occurred after both procedures but were
      significantly less frequent at 4 to 8 weeks and longer than 8 weeks after
      decompression. Twelve hematomas occurred following transposition (15%) with 1
      requiring operative debridement and 5 hematomas resolved with nonsurgical
      treatment after in situ decompression (11%). CONCLUSIONS: Ulnar nerve
      transposition imparts greater surgical morbidity than decompression with greater
      narcotic consumption, more patient-reported disability up to 8 weeks after
      surgery, and more persistent olecranon paresthesia. However, most differences in
      surgical morbidity are transient with resolution after 8 weeks following surgery.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 29223633
TI  - Effectiveness of irrigation with chlorhexidine after removal of mandibular third
      molars: a randomised controlled trial.
AB  - To evaluate the effect of postoperative irrigation with chlorhexidine on
      inflammatory complications after the extraction of lower third molars under local
      anaesthesia, we recruited 100 patients to participate in a controlled, single
      blind, randomised clinical trial. They were assigned to one of two groups: the
      intervention group (postoperative irrigation of the surgical site with
      chlorhexidine for seven days) or the control group (postoperative chlorhexidine
      mouth rinse for seven days). The primary outcome variables were pain, swelling,
      trismus, infection, and alveolar osteitis. The secondary outcome variables were
      wound dehiscence and food impaction. A total of 95 participants completed the
      study (47 in the irrigation group and 48 in the rinse group). In the irrigation
      group, alveolar osteitis and facial swelling had reduced significantly at seven
      days postoperatively (both p<0.01). Pain scores had also reduced significantly at
      seven days (p<0.01), but not at 48hours, and patients had lower levels of food
      impaction (p<0.01) and less severe symptoms (p=0.02). Routine irrigation with
      chlorhexidine after the extraction of third molars helps to reduce pain and
      lowers the incidence of alveolar osteitis.

PMID- 29223634
TI  - The composite palatal island flap: modification of an existing technique to
      reconstruct the maxillary alveolus.

PMID- 29223635
TI  - Three-dimensional superimposition for patients with facial palsy: an innovative
      method for assessing the success of facial reanimation procedures.
AB  - Facial palsy is a severe condition that may be ameliorated by facial reanimation,
      but there is no consensus about how to judge its success. In this study we aimed
      to test a new method for assessing facial movements based on 3-dimensional
      analysis of the facial surfaces. Eleven patients aged between 42 and 77 years who
      had recently been affected by facial palsy (onset between 6 and 18 months) were
      treated by an operation based on triple innervation: the masseteric to
      temporofacial nerve branch, 30% of the hypoglossal fibres to the cervicofacial
      nerve branch, and the contralateral facial nerve through two cross-face sural
      nerve grafts. Each patient had five stereophotogrammetric scans: at rest, smiling
      on the healthy side (facial stimulus), biting (masseteric stimulus), moving the
      tongue (hypoglossal stimulus), and corner-of-the-mouth smile (Mona Lisa). Each
      scan was superimposed onto the facial model of the "rest" position, and the point
      to-point root mean square (RMS) value was automatically calculated on both the
      paralysed and the healthy side, together with an index of asymmetry. One-way and
      two-way ANOVA tests, respectively, were applied to verify the significance of
      possible differences in the RMS and asymmetry index according to the type of
      stimulus (p=0.0329) and side (p<0.0001). RMS differed significantly according to
      side between the facial stimulus and the masseteric one on the paralysed side
      (p=0.0316). Facial stimulus evoked the most asymmetrical movement, whereas the
      masseteric produced the most symmetrical expression. The method can be used for
      assessing facial movements after facial reanimation.

PMID- 29223636
TI  - Revisiting lip shave: a solution for disorders of the vermilion border.
AB  - Actinic keratosis, leukoplakia, carcinoma in situ, and superficially invasive
      carcinomas of the lower lip are caused mainly by the cumulative effects of
      exposure of the vermilion of the lower lip to ultraviolet radiation. Current
      treatments all have limitations: cryosurgery or electrosurgery is suitable to
      treat only focal lesions; topical chemotherapy, which is an option for diffuse
      actinic damage, yields unreliable results; and laser treatment fails to
      rejuvenate the vermilion. However, "lip shave", which involves full-thickness
      excision of the damaged vermilion and reconstruction with an advancement labial
      mucosal flap, will produce a fresh mucosal lining to the vermilion border. We
      describe our experience of the technique and evaluate the functional and
      aesthetic outcomes in 20 patients treated between January 2011 and January 2016.
      The follow-up period ranged from 24 to 60 months. Three-quarters of the patients
      had dysplasia or superficially invasive malignancy. Resected lesions were about
      63mm long, 13.7mm wide, and 3.9mm deep. No patients had recurrence or secondary
      lesions during follow up, functional disturbance was minimal, and the cosmetic
      outcome pleasing. Lip shave can efficiently reconstruct the vermilion of the
      lower lip with minimum deformity.

PMID- 29223637
TI  - The role of striatal Galphaq/11 protein in methamphetamine-induced behavioral
      sensitization in mice.
AB  - Galphaq/11 protein transduces signals from neurotransmitter receptors and has
      been implicated in several functions of the central nervous system. In this
      study, the role of Galphaq/11 protein in methamphetamine (METH)-induced
      behavioral sensitization was investigated using neurochemical and behavioral
      approaches. Repeated treatment with METH (2mg/kg, intraperitoneally)
      significantly increased behavioral sensitization as well as Galphaq/11 protein
      expression and Galpha protein activity in the striata of mice, while a single
      treatment of METH at the same dose did not affect these parameters. Repeated
      intrastriatal injections of a Galphaq/11 inhibitor, [D-Trp7,9,10]-substance P,
      significantly reduced behavioral sensitization and striatal dopamine (DA) level
      in response to METH, with no effect on striatal tyrosine hydroxylase expression.
      These results suggest that Galphaq/11 protein facilitates METH-induced behavioral
      sensitization by modulating DA release in the mouse striatum.

PMID- 29223638
TI  - PD-L1 Expression in a Non-Small Cell Lung Cancer Specimen Obtained by EBUS-TBNA.

PMID- 29223639
TI  - Extensive phenotyping of the orofacial and dental complex in Crouzon syndrome.
AB  - OBJECTIVES: Fibroblast growth factor receptor 2 (FGFR2) C342Y/+ mutation is a
      known cause of Crouzon syndrome that is characterised by craniosynostosis and
      midfacial hypoplasia. Our aim was to conduct extensive phenotyping of the
      maxillary, mandibular and dental morphology associated with this mutation.
      MATERIALS AND METHODS: Morphometric data were obtained from 40 mice, representing
      two genotypes (Crouzon and wild-type) and two sexes (males and females) (n=10 in
      each group). Dental analysis further categorised the first molars into the two
      jaws (maxillary and mandibular) (n=20 in each group). Maxillary, mandibular and
      dental morphology was compared by analysing 23 linear landmark-based dimensions
      in three-dimensional micro-computed tomography reconstructions. RESULTS: Compared
      with wild-type, Crouzon (FGFR2C342Y/+) maxillae were significantly shorter in
      maximum height, anterior and posterior lengths and middle width, but larger in
      posterior width (p<0.05 for height; p<0.001 for other comparisons). In the
      Crouzon mandible, the ascending and descending heights, effective and mandibular
      lengths, and intercoronoid and intercondylar widths were significantly shorter,
      whereas intergonial width was larger (p<0.01 for intercondylar width; p<0.001 for
      other comparisons). Crouzon teeth were significantly smaller mesiodistally, but
      larger in crown height (p<0.001 for each comparison). All Crouzon mice presented
      with bifid mandibular condyles and a quarter presented with expansive bone
      lesions in the mandibular incisor alveolus. CONCLUSIONS: Our findings of
      hypoplasia in all three planes in Crouzon maxillae and mandibles, together with
      the presence of bifid mandibular condyles and expansive bone lesions, may be
      relevant to maxillofacial surgery and orthodontics. Beyond skeletal effects, the
      FGFR2C342Y/+ mutation is now implicated in affecting tooth development. This
      study's skeletal phenomics data also provides baseline data against which the
      effect of various treatments can now be assessed.

PMID- 29223640
TI  - Dentin sialophosphoprotein expression in enamel is regulated by Copine-7, a
      preameloblast-derived factor.
AB  - OBJECTIVE: Dentin sialophosphoprotein (Dspp) is expressed in odontoblasts and
      transiently expressed in early ameloblasts. However, the origin of Dspp in
      ameloblasts remains unclear. Our previous studies demonstrated that copine-7
      (CPNE7), a molecule that is secreted by the dental epithelium, is expressed in
      early ameloblasts and is then translocated to differentiating odontoblasts; its
      expression levels correlate with odontoblast differentiation under the control of
      Dspp expression. The objective of this study is to figure out the relationship
      between CPNE7 and Dspp during amelogenesis. DESIGN: The gene expression patterns
      of CPNE7 and dentin sialoprotein (DSP) were examined by immunohistochemistry,
      western blot analysis, and real-time polymerase chain reaction. The effects of
      CPNE7 on Dspp regulation were investigated using luciferase and chromatin
      immunoprecipitation assays in ameloblastic HAT-7 cells. RESULTS: The gene
      expression pattern of Cpne7 was similar to that of Dspp during ameloblast
      differentiation. Moreover, Gene expression omnibus profiles indicated that there
      is a close correlation between Cpne7 and Dspp expression in various normal human
      tissues. We also confirmed the effects of CPNE7 on the induction of Dspp in
      ameloblastic HAT-7 cells. Cpne7 overexpression promoted Dspp expression, whereas
      Dspp expression was down-regulated by Cpne7 inactivation. CONCLUSIONS: These
      results suggest that the expression of Dspp in early amelogenesis is linked to
      CPNE7, a preameloblast-derived factor.

PMID- 29223641
TI  - Re-irradiation for Locally Recurrent Lung Cancer: Evidence, Risks and Benefits.
AB  - In spite of recent improvements in both the technical delivery of radiotherapy
      and systemic therapy in the treatment of non-small cell lung cancer, local
      recurrence rates after radiotherapy remain a significant challenge. In the
      setting of local relapse after radiotherapy, treatments such as surgical
      resection or radiofrequency ablation are often not appropriate owing to disease
      and patient factors. Re-irradiation may be a potential treatment option. This
      overview considers the published evidence and potential treatment strategies.

PMID- 29223642
TI  - Fighting Resilient Cancers with Iron.
AB  - Tumor progression and resistance to treatment are often accompanied by the
      polarization of malignant cells towards a mesenchymal or poorly differentiated
      state. Such a transition generates an accrued vulnerability to the induction of
      ferroptosis, potentially paving the way to novel therapeutic strategies for
      targeting residual disease in patients with cancer.

PMID- 29223643
TI  - Povidone iodine soaked gelfoam for the treatment of recalcitrant otomycosis - Our
      experiences at a tertiary care teaching hospital of eastern India.
AB  - INTRODUCTION: Otomycosis is a common clinical condition seen in outpatient
      department of otorhinolaryngology. The treatment of the otomycosis is also very
      simple. However, sometime it is difficult to treat otomycosis along with mastoid
      cavity, chronic suppurative otitis media, immunocompromised patient, etc. with
      conventional treatment, called recalcitrant otomycosis. Here, we describe a
      technique of treatment for recalcitrant otomycosis. MATERIALS AND METHODS: This
      is a prospective observational study/clinical trial carried out on 44 patients of
      recalcitrant otomycosis. They are divided into two groups, each of 22. One group
      treated with routine clotrimazole topical eardrops whereas other group treated
      with povidone iodine soaked gelfoam, placed in the external auditory canal.
      RESULTS: There was no significance difference according to the age (P=0.134),
      gender (P=0.760) and causative agents (P=0.750) between treatment groups. The
      resolution of the symptoms showed statistically significant on itching
      (P=0.0001), otorrhoea (P=0.0033), fullness (P=0.0432) and earache (P=0.0259),
      whereas no statistical significant on hearing loss (P=0.0683), when treating with
      povidone iodine soaked gelfoam as compared to routine (clotrimazole) treatment.
      Resolution of signs like canal wall erythema (P=0.0045), tragal tenderness
      (P=0.0012) and congestion of tympanic membrane (P=0.0088) is statistically
      significant when comparing clotrimazole with povidone iodine. Apart from these,
      we did not reveal any adverse effects from the study populations treated with
      povidone iodine soaked gelfoam. CONCLUSION: Use of the povidone iodine soaked
      gelfoam at the external auditory canal in recalcitrant otomycosis is an effective
      and well-tolerated treatment.

PMID- 29223644
TI  - Functional significance of O-GlcNAc modification in regulating neuronal
      properties.
AB  - Post-translational modifications (PTMs) covalently modify proteins and diversify
      protein functions. Along with protein phosphorylation, another common PTM is the
      addition of O-linked beta-N-acetylglucosamine (O-GlcNAc) to serine and/or
      threonine residues. O-GlcNAc modification is similar to phosphorylation in that
      it occurs to serine and threonine residues and cycles on and off with a similar
      time scale. However, a striking difference is that the addition and removal of
      the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless
      of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. O
      GlcNAcylation can interact or potentially compete with phosphorylation on serine
      and threonine residues, and thus serves as an important molecular mechanism to
      modulate protein functions and activation. However, it has been challenging to
      address the role of O-GlcNAc modification in regulating protein functions at the
      molecular level due to the lack of convenient tools to determine the sites and
      degrees of O-GlcNAcylation. Studies in this field have only begun to expand
      significantly thanks to the recent advances in detection and manipulation methods
      such as quantitative proteomics and highly selective small-molecule inhibitors
      for OGT and OGA. Interestingly, multiple brain regions, especially hippocampus,
      express high levels of both OGT and OGA, and a number of neuron-specific proteins
      have been reported to undergo O-GlcNAcylation. This review aims to discuss the
      recent updates concerning the impacts of O-GlcNAc modification on neuronal
      functions at multiple levels ranging from intrinsic neuronal properties to
      synaptic plasticity and animal behaviors.

PMID- 29223645
TI  - Amino acid supplements in critically ill patients.
AB  - Observational studies have associated a low amino acid intake with adverse
      outcome of critical illness. Although this finding could theoretically be
      explained by differences in feeding tolerance related to illness severity,
      guidelines have recommended to administer sufficient amounts of amino acids from
      early onwards in the disease course. Recently, however, several high quality
      randomized controlled trials have not shown benefit by early amino acid
      supplementation and some trials even found potential harm, thus questioning this
      recommendation. These negative results could be related to amino acid-induced
      suppression of autophagy, to the inability to suppress bulk catabolism by
      exogenous amino acids, or to the administration of an amino acid mixture with an
      inappropriate composition. Currently, there is no evidence supporting
      administration of individual amino acid supplements during critical illness and
      glutamine administration may be harmful. The optimal timing, dose and composition
      of the amino acid mixture for critically ill patients remain unclear.

PMID- 29223646
TI  - Exploring the effects of DPP-4 inhibitors on the kidney from the bench to
      clinical trials.
AB  - Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non
      insulin glucose-lowering agents, belonging to the incretin family, which are able
      to improve glycemic control with a favorable safety profile, since they are
      associated with a low risk of hypoglycemia, no weight gain, and good tolerability
      in patients with chronic renal failure. Some experimental and clinical studies
      suggest that these drugs may exert significant pleiotropic effects, in particular
      on chronic kidney disease (CKD) progression, but data from clinical trials are
      still controversial. In an effort to clarify the effects of DPP-4 inhibitors (DPP
      4is) on diabetes-related renal damage, we performed a narrative review of
      available clinical trials and other experimental studies focusing on renal
      effects of DPP-4is. Currently, there is no conclusive evidence proving the
      usefulness of this drug class for improving diabetes-related renal damage.
      However, our literature review suggests that DPP-4is are safe and well tolerated
      in type 2 diabetes mellitus (T2DM) patients with CKD. More importantly, results
      from the reviewed studies indicate that DPP-4 inhibitor therapy may improve two
      major risk factors for diabetic nephropathy, such as hyperglycemia and
      albuminuria, resulting in potential renal benefits beyond glycemic control.
      Despite several limitations, the conclusions of our review corroborate previous
      evidence on the potential renal benefits of DPP-4is, highlighting the urgent need
      of future trials adequately powered and designed on hard renal outcomes to
      ascertain (or contradict) the therapeutic benefit of DPP-4is in T2DM and CKD
      patients.

PMID- 29223647
TI  - TAT-conjugated chitosan cationic micelle for nuclear-targeted drug and gene co
      delivery.
AB  - We developed a high-efficiency nucleus-targeted co-delivery vector that delivers
      genes and drugs directly into the nucleus of cancer cells. The system is based on
      grafted poly-(N-3-carbobenzyloxy-lysine) (CPCL) with transactivator of
      transcription (TAT)- chitosan on the surface. It is designed to perform highly
      efficient nucleus- targeted gene and drug co-delivery. Confocal laser scanning
      microscopy (CLSM) revealed that more TAT-CPCL entered the nucleus than does CPCL
      alone. The TAT-modified vector serves as a gene and drug co-delivery mechanism to
      achieve high gene transfection efficiency, high apoptosis and low viability in
      HeLa cells. TAT-CPCL may become a vector for cancer gene treatment and a template
      for designing better co-deliver systems.

PMID- 29223648
TI  - Antimicrobial eugenol-loaded electrospun membranes of poly(epsilon
      caprolactone)/gelatin incorporated with REDV for vascular graft applications.
AB  - Confronted with the risk of stenosis and bacterial infection, vascular grafts are
      necessarily required with rapid endothelialization and antibacterial activity. In
      this work, dual-functional electrospun membranes of poly(epsilon-caprolactone)
      (PCL)/gelatin were developed. A short active peptide, REDV, was covalently
      conjugated with a low molecular weight PCL to obtain REDV-PCL-REDV, which was
      introduced into the electrospun fibers to improve the adhesion and proliferation
      of vascular endothelial cells (VECs) on the electrospun membranes. Additionally,
      a plant-extracted antibacterial agent, eugenol, was loaded for the antibacterial
      purpose. Results suggested that the electrospun membranes demonstrated acceptable
      mechanical properties and release profiles. The electrospun membrane containing
      30% of eugenol could inhibit Escherichia coli and Staphylococcus aureus with
      71.6+/-3.3% and 78.6+/-2.5% of growth inhibition rates, respectively. Further
      results showed all the electrospun membranes exhibited lower cytotoxicity towards
      L929 fibroblasts with more than 80% of relative cell viability. The VEC culture
      assays indicated that the REDV-modified electrospun membranes by the
      incorporation of REDV-PCL-REDV could significantly promote VEC adhesion and
      proliferation. Therefore, the dual-functional electrospun membranes with
      endothelialization and antibacterial abilities by incorporating REDV and eugenol
      could be potentially applied as promising vascular grafts.

PMID- 29223649
TI  - Novel liposome-based and in situ gelling artificial tear formulation for dry eye
      disease treatment.
AB  - PURPOSE: Artificial tears are widely used in the treatment of dry eye disease,
      although current formulations do not closely resemble natural tears. The purpose
      of this study was the design and characterization of a novel in situ gelling
      artificial tear formulation, containing both lipid and aqueous components, in
      order to resemble natural tears and replenish the tear film. METHODS: Liposomes,
      containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by
      the thin-film hydration method. The aqueous phase of the formulation was
      comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine,
      electrolytes (sodium chloride and potassium chloride), trehalose, and borates.
      The artificial tear was characterized in terms of liposome size, pH, surface
      tension, and viscosity. In vitro tolerance studies were performed in a human
      epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774).
      In vivo tolerance was assessed in rabbits. RESULTS: Liposomes presented a
      unimodal distribution with a mean size of 200.1 +/- 4.4 nm. The resulting surface
      tension was 53.4 +/- 1.1 mN/m (at 33  degrees C) and the pH was 7.6 +/- 0.1. The
      viscosity of the formulation presented a mean value of 4.0 +/- 0.1 mPa s within
      the shear rate interval of 200-1000 s-1 at 33  degrees C. Cell viability remained
      higher than 90% in both cell lines. No discomfort or clinical signs were observed
      in rabbits. CONCLUSIONS: The liposome-based and in situ gelling artificial tear
      formulation presented good tolerance and suitable properties for topical
      ophthalmic administration. It may be beneficial in the treatment of dry eye
      disease.

PMID- 29223650
TI  - Dry eye following cataract surgery: The effect of light exposure using an in
      vitro model.
AB  - PURPOSE: Cataract surgery can lead to the temporary development or worsening of
      dry eye symptoms. Contributing factors may include corneal incisions, agents used
      before, during or after surgery, light from the operating microscope, disruption
      of ocular surface tissues and inflammatory processes. The purpose of this study
      was to observe the effect of light exposure on conjunctival fibroblasts in order
      to determine whether light has an effect on wound healing closure, assuming that
      operating microscopes might have an effect on the ocular surface. METHOD: An in
      vitro scratch assay was performed on porcine conjunctival fibroblasts. Ten
      minutes of light exposure from a light microscope with a halogen bulb was
      performed after the scratch assay. Fibroblasts were kept in culture for 48 hours
      post-exposure and the wound closure rates were visualized by live/dead staining.
      The fibroblasts which were exposed to light were compared to those without light
      exposure. Cell viability was also analysed by MTT assay. RESULTS: A Slower wound
      closure rate was found when fibroblasts were exposed to light compared to the non
      light exposed controls. Cell viability reduced by 20% with light exposure
      compared to controls in p3 cells (p = 0.04; however, the trend was not observed
      with p4 and p5 cells (p > 0.05). CONCLUSIONS: These results suggest that light
      exposure might be one of the possible contributory factors for dry eye after
      ophthalmic surgery. Further evaluation of light effects should be carried out
      with different ocular surface cells.

PMID- 29223651
TI  - Effects of the rigid gas permeable contact lense use on tear and ocular surface
      among keratoconus patients.
AB  - PURPOSE: To investigate changes in tear and ocular surface of patients with
      keratoconus using rigid gas permeable contact lenses (RGPCL) and compare them
      against keratoconus patients who were not using lenses as well as a control group
      of healthy subjects. METHODS: 24 keratoconus patients using RGPCL (Group 1) 22
      patients who were not using lenses (Group 3) and 21 healthy subjects (Group 3)
      were included in the study. Subjective complaints about the subjects' eyes have
      been investigated using the ocular-surface disease index (OSDI). After the
      control of best-corrected visual acuity, anterior chamber and fundus examinations
      were performed. RESULTS: Schirmer (p-value=0.01) and tear break up mean
      comparison tests (p-value=0.002) revealed significant differences across
      different groups but tear osmolarity analysis did not (p-value >0.05). Oxford and
      OSDI scores were compatible with Schirmer and tear break up test comparisons.
      (for both p-value=0.001) Moreover, no statistical differences were seen in
      impression cytology measures between groups. (p-value >0.05) CONCLUSIONS: The
      erosion in the tear film stability is in line with the erosion in the ocular
      surface epithelium. Taking into account the statistical indifference between the
      impression cytology measures across groups, the break up time differences may be
      attributed to the collagen destruction in tear.

PMID- 29223652
TI  - No effect of fampridine on real-life physical activity in people with multiple
      sclerosis.

PMID- 29223653
TI  - Heart rate recovery of individuals undergoing cardiac rehabilitation after acute
      coronary syndrome.
AB  - BACKGROUND: An efficient cardiac rehabilitation programme (CRP) can improve the
      functional ability of patients after acute coronary syndrome (ACS). OBJECTIVE: To
      examine the effect of a CRP on parasympathetic reactivation and heart rate
      recovery (HRR) measured after a 6-min walk test (6MWT), and correlation with 6MWT
      distance and well-being after ACS. METHODS: Eleven normoweight patients after ACS
      (BMI<25kg/m2; 10 males; mean [SD] age 61 [9] years) underwent an 8-week CRP.
      Before (pre-) and at weeks 4 (W4) and 8 (W8) during the CRP, they performed a
      6MWT on a treadmill, followed by 10-min of seated passive recovery, with HRR and
      HR variability (HRV) recordings. HRR was measured at 1, 3, 5 and 10min after the
      6MWT (HRR1, HRR3, HRR5, HRR10), then modelized by a mono-exponential function.
      Time-domain (square root of the mean of the sum of the squares of differences
      between adjacent normal R-R intervals [RMSSD]) and frequency-domain (with high-
      and low-frequency band powers) were used to analyse HRV. Participants completed a
      mental and physical well-being questionnaire at pre- and W8. Exhaustion after
      tests was assessed by the Borg scale. Pearson correlation was used to assess
      correlations. RESULTS: HRR3, HRR5 and HRR10 increased by 37%, 36% and 28%,
      respectively, between pre- and W8 (P<0.05), and were positively correlated with
      change in 6MWT distance (r=0.58, 0.66 and 0.76; P<0.05). Percentage change in
      HRR3 was positively correlated with change in well-being (r=0.70; P=0.01).
      Parasympathic reactivation (RMSSD) was improved only during the first 30sec of
      recovery (P=0.04). CONCLUSION: Among patients undergoing a CRP after ACS,
      increased HRR after a 6MWT, especially at 3min, was positively correlated with
      6MWT distance and improved well-being. HRR raw data seem more sensitive than post
      exercise HRV analysis for monitoring functional and autonomic improvement after
      ACS.

PMID- 29223654
TI  - Formulation, physical, in vitro and ex vivo evaluation of nanomedicine-based
      chemosterilant for non-surgical castration of male animals.
AB  - The overpopulation of free-roaming companion animals has become the global
      crisis. The development and application of a suitable, effective, non-surgical
      approach for animal sterilization would have an enormous advantage over the
      current surgical method. The main purpose of this study was to develop and
      evaluate a novel nanomedicine-based chemosterilant for non-surgical castration of
      male companion animals. In this study, we first sought to investigate the
      testicular toxicity of different apoptosis-inducing agents. We next synthesized
      and characterized nano-sized particles which encapsulated the most potent
      testicular toxicants and evaluated in vitro sterilant properties. Our result
      showed that doxorubicin exhibited the highest cytotoxic activity against mouse
      spermatogenic cells. We therefore synthesized and characterized doxorubicin
      encapsulated nanoemulsion. The negatively charged particle of doxorubicin
      encapsulated nanoemulsion exhibited the anti-proliferative activity towards
      spermatogetic cells. Apoptosis studies revealed activation of Caspases 3 and 7 as
      well as annexin V expression. In addition, doxorubicin-encapsulated nanoemulsion
      exhibited anti-inflammatory activity in lipopolysaccharide-stimulated
      macrophages. Cell death was observed following treatment of isolated and cultured
      rat seminiferous tubules with doxorubicin-encapsulated nanoemulsion. In
      conclusion, nanoemulsion can be a potential carrier for prolonged release and to
      enhance activity of doxorubicin that may have utility in non-surgical castration
      of male animals.

PMID- 29223655
TI  - In vitro cultured bovine endometrial cells recognize embryonic sex.
AB  - Endometrial cell co-culture (ECC) with single embryo may reflect endometrium
      responses in vivo. Bovine Day-6 in vitro-produced morulae were cultured until Day
      8 in modified synthetic oviductal fluid (mSOF), or on the epithelial side of ECC.
      Expression of epithelial- and stromal-cell transcripts was analyzed by RT-PCR in
      ECC with one male (ME) or female embryo (FE). Concentrations of ARTEMIN (ARTN)
      and total protein were determined in epithelial cell-conditioned medium. ECCs
      yielded embryos with more cells in the inner cell mass than embryos cultured in
      mSOF. Embryos altered transcript expression only in epithelial cells, not in
      stromal ones. Thus, ME induced larger reductions than FE and controls (i.e., no
      embryos cultured) in hexose transporter solute carrier family 2 member 1 (SLC2A1)
      and member 5 (SLC2A5), connective tissue growth factor (CTGF), artemin (ARTN),
      and interferon alpha and beta receptors subunit IFNAR1 and IFNAR2. FE reduced
      SLC2A1 and SLC2A5, and increased ARTN expression with respect to controls. ME
      tended to reduce total protein concentration (P < 0.082) in ECC-conditioned
      medium, while ARTN protein and gene expressions strongly correlated (R > 0.90; P
      < 0.05) in the group of ME or FE, but not in controls (without embryo). Isolated
      male and female embryos may differentially release signaling factors that induce
      sexually dimorphic responses in endometrial cells.

PMID- 29223656
TI  - Endometrial expression of estrogen and progesterone receptors in non-cyclic mares
      treated only with long-acting progesterone.
AB  - Administration of progesterone (P4) after estradiol is usually performed to
      prepare non-cyclic mares as embryo recipients. However, there are successful
      pregnancy reports after embryo transfer in non-cyclic mares treated only with
      progestins. The objective of this study was to evaluate endometrial gene
      expression and immunostaining for estrogen receptor alpha (ERalpha), beta
      (ERbeta) and progesterone receptor (PR) in seasonal anestrous mares treated with
      long acting P4 (LA P4). Endometrial tissue from eight seasonal anestrous mares
      was collected immediately before administration of 1.5 g of LA P4 and five days
      after. The receptors protein expression was evaluated by immunohistochemistry and
      the percentage of the immunostained area was determined by ImageJ software.
      Transcripts abundance for ERalpha, ERbeta and PR were determined by RT-qPCR.
      Blood samples were collected daily to measure plasma P4 concentrations. Protein
      expression for ERalpha was greater (p < 0.05) after LA P4 administration,
      although gene expression was not affected by treatment (p > 0.05). There was no
      difference for ERbeta protein expression (p = 0.07) and ERbeta gene expression
      was reduced (p < 0.05) after treatment. Gene and protein expression for PR was
      not altered (p > 0.05). In conclusion, endometrial PR and ERalpha expression
      patterns after LA P4 administration were similar to those previously found in
      protocols using estradiol prior to LA P4 to prepare non-cyclic mares as embryo
      recipients.

PMID- 29223657
TI  - The "evolutionary field" hypothesis. Non-Mendelian transgenerational inheritance
      mediates diversification and evolution.
AB  - Epigenetics is increasingly regarded as a potential contributing factor to
      evolution. Building on apparently unrelated results, here I propose that RNA
      containing nanovesicles, predominantly small regulatory RNAs, are released from
      somatic tissues in the bloodstream, cross the Weismann barrier, reach the
      epididymis, and are eventually taken up by spermatozoa; henceforth the
      information is delivered to oocytes at fertilization. In the model, a LINE-1
      encoded reverse transcriptase activity, present in spermatozoa and early embryos,
      plays a key role in amplifying and propagating these RNAs as extrachromosomal
      structures. It may be conceived that, over generations, the cumulative effects of
      sperm-delivered RNAs would cross a critical threshold and overcome the buffering
      capacity of embryos. As a whole, the process can promote the generation of an
      information-containing platform that drives the reshaping of the embryonic
      epigenetic landscape with the potential to generate ontogenic changes and
      redirect the evolutionary trajectory. Over time, evolutionary significant, stably
      acquired variations could be generated through the process. The interplay between
      these elements defines the concept of "evolutionary field", a self-consistent,
      comprehensive information-containing platform and a source of discontinuous
      evolutionary novelty.

PMID- 29223658
TI  - Can technology really help to reduce underage drinking? New evidence on the
      effects of false ID laws with scanner provisions.
AB  - In Volume 36 of this journal, Yoruk (2014) uses data from the National
      Longitudinal Survey of Youth 1997 and finds that false ID laws with scanner
      provisions have large impacts on binge drinking participation, frequency of
      alcohol consumption and binge drinking frequency among minors. This paper
      reexamines how false ID laws with scanner provisions affect underage drinking. I
      first demonstrate that analyses based on NLSY97 data fail falsification exercises
      testing for significant pre-intervention effects, and that the estimated effects
      based on these data are highly sensitive to the inclusion of a lead term and to
      sample selection, which weakens confidence in the large estimated effects
      reported in Yoruk (2014). I then use data from the Youth Risk Behavior
      Surveillance System to show that false ID laws with scanner provisions have no
      effect on underage drinking behavior.

PMID- 29223659
TI  - Complications in the treatment of mandibular condylar fractures: Surgical versus
      conservative treatment.
AB  - OBJECTIVES: In the present article, we aim to review the main intra- and post
      operative complications associated with two different therapeutic approaches for
      treating mandibular condylar fractures: conservative (CTR) and surgical treatment
      (ORIF, Open Reduction and Internal Fixation). MATERIAL AND METHODS: We have
      carried out a retrospective, meta-analytic, observational study using literature
      review, covering the period between 2000- September 2017. The data obtained were
      processed using statistical software SPSS v.0.18 and R v.2.11.1. The chi-squared
      test was used for comparison of relative frequencies for independent samples.
      RESULTS: A total of 2458 patients with 2810 fractures were collected for study.
      Patients treated with CTR and ORIF were an average of 29 years old, of those
      treated with CTR, 72.37% and 27.63% were male or female respectively and, of
      those treated with ORIF, 70.36% and 29.64% were male or female respectively. The
      main complications suffered by CTR and ORIF patients were: asymmetry
      (10.2%/6.4%), residual pain (6.5%/5.6%), temporomandibular joint and articular
      imbalance (15.9%/10.3%) and malocclusion (11.1%/4.0%), respectively. We only
      found significant differences between CTR and ORIF in the number of cases of
      temporomandibular joint and articular imbalance and malocclusion. Facial nerve
      damage was found exclusively among ORIF patients (8.6%) of which 8.3% were
      temporary and 0.3% permanent. CONCLUSIONS: The complications associated with
      either technique are minimal and infrequent, resulting in successful outcomes
      with minimal morbidity. CTR are associated with complications deriving from
      delayed mobilization leading to functional limitation, whereas the main
      complication associated with ORIF treatment was facial nerve damage.

PMID- 29223660
TI  - Developing nursing and midwifery students' capacity for coping with bullying and
      aggression in clinical settings: Students' evaluation of a learning resource.
AB  - An innovative blended learning resource for undergraduate nursing and midwifery
      students was developed in a large urban Australian university, following a number
      of concerning reports by students on their experiences of bullying and aggression
      in clinical settings. The blended learning resource included interactive online
      learning modules, comprising film clips of realistic clinical scenarios, related
      readings, and reflective questions, followed by in-class role-play practice of
      effective responses to bullying and aggression. On completion of the blended
      learning resource 210 participants completed an anonymous survey (65.2% response
      rate). Qualitative data was collected and a thematic analysis of the
      participants' responses revealed the following themes: 'Engaging with the blended
      learning resource'; 'Responding to bullying' and 'Responding to aggression'. We
      assert that developing nursing and midwifery students' capacity to effectively
      respond to aggression and bullying, using a self-paced blended learning resource,
      provides a solution to managing some of the demands of the clinical setting. The
      blended learning resource, whereby nursing and midwifery students were introduced
      to realistic portrayals of bullying and aggression in clinical settings,
      developed their repertoire of effective responding and coping skills for use in
      their professional practice.

PMID- 29223661
TI  - [Is cancer incidence different between type 2 diabetes patients compared to non
      diabetics in hemodialysis? A study from the REIN registry].
AB  - BACKGROUND AND OBJECTIVES: In France, diabetes mellitus is now the second cause
      of end stage renal disease. In a large previous French national study, we
      observed that dialyzed diabetics have a significant lower risk of death by
      cancer. This first study was focused on cancer death but did not investigate
      cancer incidence. In this context, the aim of this second study was to compare
      the incidence of cancer in diabetic dialyzed patients compared to non-diabetic
      dialyzed patients in a French region. METHODS: This epidemiologic multicentric
      study included 588 diabetic and non-diabetic patients starting hemodialysis
      between 2002 and 2007 in Bretagne. Data were issued from REIN registry and cancer
      incidence were individually collected from medical records. Diabetics and non
      diabetics were matched one by one on age, sex and year of dialysis initiation.
      RESULTS: During the follow-up, we observed 28 cancers (9.4%) in diabetic patients
      and 26 cancers (8.9%) in non-diabetics patients. The cumulative incidence to
      develop a cancer 2 years after the dialysis start was approximately 6% in both
      diabetics and non-diabetics patients. In univariate Fine and Gray analysis, BMI,
      hemoglobin, statin use had P-value<0.2. However, in the adjusted model, these
      variables were not significantly associated with cancer incidence. CONCLUSION:
      This study lead on a little number of dialyzed patients did not show any
      significant difference on cancer incidence between diabetic and non-diabetic
      patients after hemodialysis start.

PMID- 29223662
TI  - [Discrepancies (and confluences) in perception between patients and nephrologists
      of chronic kidney disease impact on vital impetus in adults not undergoing
      hemodialysis: Results of the French MAEVA study].
AB  - RATIONALE: The impact of chronic kidney disease (CKD) on vital impetus is poorly
      documented in patients not undergoing renal dialysis and discrepancies can be
      observed between patients and physicians in perception of QoL and impact of the
      disease. METHODS: A self-questionnaire was sent to 1282 French nephrologists and
      a mirrored self-questionnaire was given to patients (CKD stage 3, 4 or 5) by
      their nephrologist. Data were collected prospectively and anonymously. RESULTS: A
      total of 261 nephrologists and 172 patients participated in the survey. Sixty-six
      percent of patients reported a negative impact of the disease on their quality of
      life, which is also identified by nephrologists: important impact 22% vs 27%,
      mild or inconstant 44% vs 47%, mild or absent 34% vs 31% in patients and
      nephrologists, respectively. They had different perceptions about factors
      contributing to vital force; in particular, nephrologists underestimated their
      key role in psychological support. Indeed, the optimism and encouragements of
      nephrologists were considered to be a key factor of vital force for 60% of
      patients vs 20% of nephrologists (P<0,001). During consultations, nephrologists
      were primarily focused on biological abnormalities and adherence to treatment
      while mood or sexual disorders were rarely investigated. The main objective of
      treatment was to maintain a normal life for patients and to delay dialysis for
      nephrologists. CONCLUSION: Nephrologists have a relative knowledge of CKD impact
      on the vital impetus of patients, but there are differences of perception. It
      could be improved through specific trainings.

PMID- 29223663
TI  - Patch esophagoplasty using an in-body-tissue-engineered collagenous connective
      tissue membrane.
AB  - AIM: Although many approaches to esophageal replacement have been investigated,
      these efforts have thus far only met limited success. In-body-tissue-engineered
      connective tissue tubes have been reported to be effective as vascular
      replacement grafts. The aim of this study was to investigate the usefulness of an
      In-body-tissue-engineered collagenous connective tissue membrane, "Biosheet", as
      a novel esophageal scaffold in a beagle model. METHODS: We prepared Biosheets by
      embedding specially designed molds into subcutaneous pouches in beagles. After 1
      2months, the molds, which were filled with ingrown connective tissues, were
      harvested. Rectangular-shaped Biosheets (10*20mm) were then implanted to replace
      defects of the same size that had been created in the cervical esophagus of the
      beagle. An endoscopic evaluation was performed at 4 and 12weeks after
      implantation. The esophagus was harvested and subjected to a histological
      evaluation at 4 (n=2) and 12weeks (n=2) after implantation. The animal study
      protocols were approved by the National Cerebral and Cardiovascular Centre
      Research Institute Committee (No. 16048). RESULTS: The Biosheets showed
      sufficient strength and flexibility to replace the esophagus defect. All animals
      survived with full oral feeding during the study period. No anastomotic leakage
      was observed. An endoscopic study at 4 and 12weeks after implantation revealed
      that the anastomotic sites and the internal surface of the Biosheets were smooth,
      without stenosis. A histological analysis at 4weeks after implantation
      demonstrated that stratified squamous epithelium was regenerated on the internal
      surface of the Biosheets. A histological analysis at 12weeks after implantation
      showed the regeneration of muscle tissue in the implanted Biosheets. CONCLUSION:
      The long-term results of patch esophagoplasty using Biosheets showed regeneration
      of stratified squamous epithelium and muscular tissues in the implanted sheets.
      These results suggest that Biosheets may be useful as a novel esophageal
      scaffold.

PMID- 29223664
TI  - Summary of the British Association of Paediatric Surgeons 64th Annual Congress.
AB  - : This is a review of the joint 64th British Association of Paediatric Surgeons
      (BAPS) and 26th International Pediatric Endosurgery Group (IPEG) Annual
      Conference, which was held in July 2017, in London, UK. More than 200 papers were
      presented either orally or as posters in the BAPS section, and it was the largest
      paediatric surgical conference in Europe in 2017. The congress issue contains
      papers and posters presented during the open sessions and transcripts based on
      invited lectures. LEVEL OF EVIDENCE: IV.

PMID- 29223665
TI  - Guidelines and checklists for short-term missions in global pediatric surgery:
      Recommendations from the American Academy of Pediatrics Delivery of Surgical Care
      Global Health Subcommittee, American Pediatric Surgical Association Global
      Pediatric Surgery Committee, Society for Pediatric Anesthesia Committee on
      International Education and Service, and American Pediatric Surgical Nurses
      Association, Inc. Global Health Special Interest Group.
AB  - INTRODUCTION: Pediatric surgeons, anesthesia providers, and nurses from North
      America and other high-income countries (HICs) are increasingly engaged in
      resource-limited areas, with short-term missions (STMs) as the most common form
      of involvement. However, consensus recommendations currently do not exist for
      STMs in pediatric general surgery and associated perioperative care. METHODS: The
      American Academy of Pediatrics (AAP) Delivery of Surgical Care Subcommittee and
      American Pediatric Surgical Association (APSA) Global Pediatric Surgery
      Committee, with the American Pediatric Surgical Nurses Association, Inc. (APSNA)
      Global Health Special Interest Group, and the Society for Pediatric Anesthesia
      (SPA) Committee on International Education and Service generated consensus
      recommendations for STMs based on extensive experience with STMs. RESULTS: Three
      distinct, but related areas were identified: 1) Broad goals of surgical
      partnerships between HICs- and low and middle-income countries (LMICs). A
      previous set of guidelines published by the Global Paediatric Surgery Network
      Collaborative (GPSN), was endorsed by all groups; 2) Guidelines for the conduct
      of STMs were developed, including planning, in-country perioperative patient
      care, post-trip follow-up, and sustainability; 3) travel and safety
      considerations critical to STM success were enumerated. CONCLUSION: A diverse
      group of stakeholders developed these guidelines for STMs in LMICs. These
      guidelines may be a useful tool to ensure safe, responsible, and ethical STMs
      given increasing engagement of HIC providers in this work. LEVEL OF EVIDENCE: 5.

PMID- 29223666
TI  - Laparoscopic versus open appendectomy in children: a randomized controlled trial
      from a developing country.
AB  - BACKGROUND: Acute appendicitis is a common surgical emergency. This study was
      conducted to compare the outcome in terms of duration of surgery, length of
      hospital stay, and wound infection rate following laparoscopic versus open
      appendectomy in children with acute appendicitis. METHODS: A prospective
      randomized controlled trial was conducted. Patients with the diagnosis of acute
      appendicitis were randomly assigned to Group A: Laparoscopic appendectomy (LA)
      and Group B: Open appendectomy (OA). Age and sex of patients, signs, and symptoms
      were noted. Duration of surgery, length of hospital stay (LOS), and postoperative
      wound infection were recorded. RESULTS: A total of 126 patients were operated,
      with 63 in each group. Mean age of the patients was 9.7+/-2.1years in LA group
      and 9.8+/-2.3years in OA group. In LA group, inflamed appendix was found in 68%
      patients, perforated in 17%, gangrenous in 9%, and suppurative in 5%. In OA
      group, inflamed appendix was found in 60% patients, perforated in 22%, gangrenous
      in 5%, and suppurative in 13%. The mean duration of operation was 56+/-24min in
      LA group and 39+/-8min in OA group (p<0.0001 in favor of OA group). The mean
      length of hospital stay was 34+/-13h in LA group and 40+/-11h in OA group (p=0.01
      in favor of LA group). The results showed no significant association of wound
      infection between the two groups (p=0.31). CONCLUSION: There was no difference in
      terms of LOS and rate of wound infection among the groups. However, the
      laparoscopic procedure was technically demanding. LEVEL OF EVIDENCE: Level I
      Randomized Controlled Trial.

PMID- 29223667
TI  - Selective versus routine patch metal allergy testing to select bar material for
      the Nuss procedure in 932 patients over 10years.
AB  - AIM OF THE STUDY: The aim of the study was to determine the role of patch metal
      allergy testing to select bar material for the Nuss procedure. METHODS: An IRB
      approved (11-04-WC-0098) single institution retrospective, cohort study comparing
      selective versus routine patch metal allergy testing to select stainless steel or
      titanium bars for Nuss repair was performed. In Cohort A (9/2004-1/2011),
      selective patch testing was performed based on clinical risk factors. In Cohort B
      (2/2011-9/2014), all patients were patch tested. The cohorts were compared for
      incidence of bar allergy and resultant premature bar loss. Risk factors for
      stainless steel allergy or positive patch test were evaluated. MAIN RESULTS:
      Cohort A had 628 patients with 63 (10.0%) selected for patch testing, while all
      304 patients in Cohort B were tested. Over 10years, 15 (1.8%) of the 842
      stainless steel Nuss repairs resulted in a bar allergy, and 5 had a negative
      preoperative patch test. The incidence of stainless steel bar allergy (1.8% vs
      1.7%, p=0.57) and resultant bar loss (0.5% vs 1.3%, p=0.23) was not statistically
      different between cohorts. An allergic reaction to a stainless steel bar or a
      positive patch test was more common in females (OR=2.3, p<0.001) and patients
      with a personal (OR=24.8, p<0.001) or family history (OR=3.1, p<0.001) of metal
      sensitivity. CONCLUSION: Stainless steel bar allergies occur at a low incidence
      with either routine or selective patch metal allergy testing. If selective
      testing is performed, it is advisable in females and patients with a personal or
      family history of metal sensitivity. A negative preoperative patch metal allergy
      test does not preclude the possibility of a postoperative stainless steel bar
      allergy. LEVEL OF EVIDENCE: Level III Treatment Study and Study of Diagnostic
      Test.

PMID- 29223668
TI  - Transumbilical extracorporeal laparoscopic-assisted appendectomy.
AB  - AIM OF THE STUDY: The perfect balance between safety, cosmesis, and cost
      effectiveness in a world with ever growing healthcare costs has yet to be found
      for nonperforated appendicitis. The aim is to present our data regarding safety
      and cost effectiveness of the transumbilical extracorporeal laparoscopic-assisted
      appendectomy technique. METHODS: A retrospective review was performed for all
      laparoscopic appendectomies for acute appendicitis from October 2014 to October
      2016. All cases of perforated appendicitis were excluded (visible
      hole/abscess/free pus). Included cases were divided into two groups by operative
      technique: transumbilical (TU) or laparoscopic 3-port (L3P). Operating room
      charges were billed in 30-min intervals, and hospital charges billed per night in
      house. The technique was that the appendix is identified with the laparoscope,
      grabbed with a grasper that is inserted parallel to the laparoscope, and
      exteriorized through the umbilicus. The appendectomy is completed
      extracorporeally. RESULTS: A total of 494 cases of nonperforated appendicitis
      were included in the study. One surgeon attempted all cases with the TU technique
      (n=161), and all other surgeons used the L3P technique (n=333), which required an
      endostapler and a vascular sealing device. The TU technique was successful in 99
      of the attempted cases. The mean operative time of the TU cases and the L3P cases
      was 21 (8-43) and 37 (12-73) min, respectively (P<0.001). The mean hospital stay
      for the TU and the L3P cases was 1.6 (1-5) days (one-night admission) and 2.4 (1
      14) days (two-night admission), respectively (P<0.001). There were no operative
      complications or readmissions in either group. The overall cost of the L3P cases
      was 30% higher than the cost of the TU cases. CONCLUSION: The transumbilical
      extracorporeal laparoscopic-assisted technique was as safe as the laparoscopic 3
      port technique. It offered all the advantages of a minimally invasive procedure,
      was associated with a significantly shorter hospital stay, and was remarkably
      more cost effective than the standard laparoscopic 3-port technique. LEVEL OF
      EVIDENCE: III.

PMID- 29223669
TI  - Experimental use of new absorbable tracheal stent.
AB  - BACKGROUND/PURPOSE: Silicone and metallic stents are not effective in children
      with tracheobronchial stenosis or tracheomalacia. Herein, we aimed to evaluate
      the clinical manifestations and histological reaction of rabbit trachea to the
      presence of a new poly(lactic-co-glycolic acid) with polyisoprene (PLGA/PI)
      polymer absorbable stent. METHODS: Fourteen adult white rabbits (weight, 3.0
      3.5kg) were randomly assigned to three groups: Group I (n=6): PLGA/PI spiral
      stent; Group II (n=6): PLGA/PI fragment; and Group III (n=2): controls. After a
      longitudinal incision on three cervical tracheal rings, the stents and fragments
      were inserted into the trachea and fixed onto the lateral wall with nonabsorbable
      sutures. RESULTS: The stented group showed significantly more stridor at rest
      (p=0.0041), agitation (p=0.014), and use of accessory muscles (p=0.0002) and
      required more emergency endoscopies than the fragment group. Further, it showed
      significantly more remarkable histological inflammatory damage than the fragment
      and control groups (p=0.002). CONCLUSIONS: The new PLGA/PI polymeric stent
      implanted into the trachea of rabbits caused more clinical manifestations and
      histologically verified inflammatory reaction than the PLGA/PI polymeric
      fragment. Future studies should be aimed at reducing the stent-wall thickness.

PMID- 29223671
TI  - Reply to letter to the editor.

PMID- 29223670
TI  - Cystourethroscopy versus contrast studies in urogenital sinus and cloacal
      anomalies in children.
AB  - BACKGROUND: Cloacal malformation is a spectrum of diseases affecting females,
      resulting in abnormal confluence of the urinary system, genital system, and/or
      gastrointestinal system. Proper reconstruction depends mainly on accurate
      preoperative illustration of the abnormal anatomy. Among the various modalities
      to delineate the urogenital sinus and the distances to confluence, lies the
      radiological contrast study, as well as the preoperative diagnostic
      cystourethroscopy. AIM OF THE STUDY: The aim of this study was to compare the
      accuracy of the contrast study and diagnostic cystourethroscopy in the
      demonstration of the exact changes in anatomy resulting from urogenital sinus /
      cloacal abnormalities. METHODS: Sixteen girls with median age 21 (11-27) months
      were studied. They included 4 girls with complete cloacal anomalies and 12 girls
      with persistent urogenital sinus secondary to congenital adrenal hyperplasia
      (CAH). Contrast studies and diagnostic cystourethroscopy were applied to all
      cases. Accuracy of both methods in delineating the abnormal anatomy was evaluated
      by comparison against intraoperative findings. Data are presented as median
      (range) or %. RESULTS: Contrast studies accurately delineated the abnormal
      anatomy in 12 (75%), cases with 50% and 85% accuracy in cases of cloacal
      anomalies and persistent urogenital sinus, respectively. Cystourethroscopy was
      overall accurate in 15 cases (94%), with accuracy of 75% in cloacal anomalies and
      100% in persistent urogenital sinus. CONCLUSION: Although the presented series is
      small, it suggests that cystourethroscopy is superior to contrast studies in
      preoperative illustration of the abnormal anatomy in cases of cloacal
      malformations. These findings warrant confirmation in larger series. TYPE OF
      STUDY: Diagnostic study. LEVEL OF EVIDENCE: II.

PMID- 29223672
TI  - Education and the pediatric surgeon.
AB  - : There have been many changes in the domain of clinical surgery over the last 2
      decades, but probably none more so than in education. The British Association of
      Pediatric Surgeons recognizes the importance of this topic and has commissioned a
      special session on this subject jointly with the International Pediatric
      Endosurgery Group. Free papers presented on a number of educational subjects and
      specific topics of recruitment and simulation were covered in invited lectures.
      The session was completed with a keynote lecture from the renowned educationalist
      Professor Roger Kneebone. LEVEL OF EVIDENCE: 5 (Expert Opinion).

PMID- 29223673
TI  - Risk stratification in pediatric perforated appendicitis: Prospective correlation
      with outcomes and resource utilization.
AB  - PURPOSE: Despite a wide spectrum of severity, perforated appendicitis in children
      is typically considered a single entity in outcomes studies. We performed a
      prospective cohort study to define a risk stratification system that correlates
      with outcomes and resource utilization. METHODS: A prospective study was
      conducted of all children operated for perforated appendicitis between May 2015
      and December 2016 at a tertiary free-standing university children's hospital.
      Surgical findings were classified into one of four grades of perforation: I.
      localized or contained perforation, II. Contained abscess with no generalized
      peritonitis, III. Generalized peritonitis with no dominant abscess, IV.
      Generalized peritonitis with one or more dominant abscesses. All patients were
      treated on a clinical pathway that involved all points of care from admission to
      final follow-up. Outcomes and resource utilization measures were analyzed using
      Fisher's exact test, Kruskal-Wallis test, One-way ANOVA, and logistic regression.
      RESULTS: During the study period, 122 patients completed treatment, and 100% had
      documented follow-up at a median of 25days after operation. Grades of perforation
      were: I, 20.5%; II, 37.7%; III, 10.7%; IV, 31.1%. Postoperative abscesses
      occurred in 12 (9.8%) of patients, almost exclusively in Grade IV perforations.
      Hospital stay, duration of antibiotics, TPN utilization, and the incidence of
      postoperative imaging significantly increased with increasing grade of
      perforation. CONCLUSION: Outcomes and resource utilization strongly correlate
      with increasing grade of perforated appendicitis. Postoperative abscesses,
      additional imaging, and additional invasive procedures occur disproportionately
      in patients who present with diffuse peritonitis and abscess formation. The
      current stratification allows risk-adjusted outcome reporting and appropriate
      assignment of resource burden. LEVEL OF EVIDENCE: I (Prognosis Study).

PMID- 29223674
TI  - Prediction of need for intervention in posterior urethral valves: Use of urine
      osmolality.
AB  - AIM: Renal tubular dysfunction (RTD) causing obligate production of hypoosmolar
      urine in boys with posterior urethral valves (PUVs) has been described. It is not
      known how clinically significant this is. We hypothesize that a feedback loop is
      present in many PUV boys who suffer deterioration of their lower urinary tract
      (LUT). RTD results in hypoosmolar urine, obligate polyuria, and bladder stretch
      injury. The increasing back-pressure worsens RTD, thus exacerbating the injury.
      Coexisting renal dysplasia and acquired renal scarring exacerbate this. We
      compared the concentrating ability (random clinic urine osmolality) of PUV boys
      who had no LUT deterioration to those who required intervention, examining the
      confounding effect of renal impairment with a subgroup analysis comparing those
      with plasma creatinine <=80MUmol/l. METHODS: A retrospective review of our PUV
      database was performed. Age, intervention, and highest recorded random clinic
      urine osmolality (>1year) with concurrent plasma creatinine were recorded (normal
      urine osmolality 500-850 mOsm/kg). Data are given as median values, analyzed by
      Mann-Whitney u-test, with P<0.05 deemed significant. MAIN RESULTS: Urine
      osmolality was available in 77 boys with PUV out of 125 in our series. Of these,
      34 required subsequent intervention (e.g., Mitrofanoff procedure, bladder
      augmentation). Age at testing trended towards being higher in the intervention
      group [7.9 (4.3-10.9) years vs. nonintervention 6.3 (4-8.4); P=0.06]. Urine
      osmolality was significantly reduced in the intervention group [411(293-547) vs.
      631 (441-805) mOsm/kg; P<0.001]. Subgroup analysis comparing only those with
      creatinine <=80MUmol/l was respectively 451 (322-567) mOsm/kg (n=22) vs. 645 (469
      810) mOsm/kg (n=40), P<0.01. CONCLUSION: This study confirms that hypoosmolar
      urine is highly associated with progression of LUT dysfunction, requiring
      intervention. Even boys with normal creatinine values have a greater risk of LUT
      deterioration if they have a RTD and produce hypoosmolar urine. LEVEL OF
      EVIDENCE: IV (retrospective service development project).

PMID- 29223675
TI  - Long term outcome of the Bascom cleft lift procedure for adolescent pilonidal
      sinus.
AB  - PURPOSE: The purpose of this study was to assess whether adolescent patients who
      heal their pilonidal sinus disease with the Bascom cleft lift have a sustained
      result, or if younger age puts them at increased risk of relapse. METHODS: Twenty
      two consecutive patients (18 male, median age 16years at surgery) who underwent
      Bascom procedures were contacted regarding long term outcomes following surgery.
      Additional clinical data were collected from the medical records of the subjects.
      RESULTS: Seventeen of 22 (77%) patients studied were completely healed at median
      27 (range 9-268) days after a single procedure. Three of 22 (14%) required a
      second procedure during follow up. Of these, all three healed fully after the
      second procedure. Based on intention to treat, 20 of 22 (91%) patients had
      complete healing documented at a median of 31days after initial surgery. Half of
      the patients were fully healed and back to normal activities by one month and 68%
      by two months. Two patients (9%) failed surgery and had ongoing pilonidal
      disease. Fifteen of 22 (68%) patients completed a follow-up survey at a median of
      44months elapsed from surgery. All responders were fully healed, and none
      reported relapse or further surgeries. CONCLUSIONS: Excision of pilonidal sinus
      disease by the Bascom procedure resulted in lasting cure for most adolescent
      patients studied. A small proportion of patients failed to heal in the first year
      and had ongoing pilonidal disease. No late failures occurred. LEVEL OF EVIDENCE:
      Level III, nonexperimental observational study.

PMID- 29223676
TI  - Influenza vaccination and heart failure. A prioritary field of improvement.

PMID- 29223677
TI  - The hypothalamus-pituitary-gonad axis: Tales of mice and men.
AB  - Reproduction is controlled by the hypothalamic-pituitary-gonadal (HPG) axis.
      Gonadotropin-releasing hormone (GnRH) neurons play a central role in this axis
      through production of GnRH, which binds to a membrane receptor on pituitary
      gonadotrophs and stimulates the biosynthesis and secretion of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH). Multiple factors affect
      GnRH neuron migration, GnRH gene expression, GnRH pulse generator, GnRH
      secretion, GnRH receptor expression, and gonadotropin synthesis and release.
      Among them anosmin is involved in the guidance of the GnRH neuron migration, and
      a loss-of-function mutation in its gene leads to a failure of their migration
      from the olfactory placode to the hypothalamus, with consequent anosmic
      hypogonadotropic hypogonadism (Kallmann syndrome). There are also cases of
      hypogonadotropic hypogonadim with normal sense of smell, due to mutations of
      other genes. Another protein, kisspeptin plays a crucial role in the regulation
      of GnRH pulse generator and the pubertal development. GnRH is the main
      hypothalamic regulator of the release of gonadotropins. Finally, FSH and LH are
      the essential hormonal regulators of testicular functions, acting through their
      receptors in Sertoli and Leydig cells, respectively. The main features of the
      male HPG axis will be described in this review.

PMID- 29223679
TI  - Striking a chord with healthy aging: memory system cooperation is related to
      preserved configural response learning in older adults.
AB  - Evidence from tasks that primarily tap either hippocampal- or striatal-based
      memory systems suggests that although these systems often compete for control of
      behavior, aging is associated with greater cooperation between them. This may
      stem from altered prefrontal cortex function. Here, we use a configural response
      task designed to engage both memory systems to test how age affects their
      interaction with cortical regions including the prefrontal cortex. We found that
      although older and younger adults learned just as well, older adults showed
      greater initial activation in cortical networks associated with visuospatial
      action mapping and resolving conflict for competing memory representations. Older
      adults also showed greater functional coupling of the striatum with the left
      inferior frontal gyrus, in parallel with similar hippocampal coupling to ventral
      visual regions as young adults. Overall, our results support the proposal that
      aging is associated with more cooperative memory systems, but we did not find
      that greater cooperation is associated with less interaction between the
      prefrontal cortex and core memory system structures during learning.

PMID- 29223678
TI  - Protein sparing therapies in acute illness and obesity: a review of George
      Blackburn's contributions to nutrition science.
AB  - Protein sparing therapies were developed to mitigate the harms associated with
      protein-calorie malnutrition and nitrogen losses induced by either acute illness
      or hypocaloric diets in patients with obesity. We review the development of
      protein sparing therapies in illness and obesity with a focus on the pioneering
      contributions of George Blackburn, MD, PhD. He recognized that protein-calorie
      malnutrition is a common and serious clinical condition and developed new
      approaches to its treatment in hospitalized patients. His work with stable
      isotopes and with animal models provided answers about the physiological
      nutritional requirements and metabolic changes across a spectrum of conditions
      with varying degrees of stress and catabolism. This led to improvements in
      enteral and parenteral nutrition for patients with acute illness. Blackburn also
      demonstrated that lean body mass can be preserved during weight loss with
      carefully designed very low calorie treatments which became known as the protein
      sparing modified fast (PSMF). We review the role of the PSMF as part of the
      comprehensive management of obesity.

PMID- 29223680
TI  - Dysregulation of C-X-C motif ligand 10 during aging and association with
      cognitive performance.
AB  - Chronic low-grade inflammation during aging (inflammaging) is associated with
      cognitive decline and neurodegeneration; however, the mechanisms underlying
      inflammaging are unclear. We studied a population (n = 361) of healthy young and
      old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine
      ligand 10 (CXCL10) was found to be higher in older adults, compared with young,
      and negatively associated with working memory performance. This coincided with an
      age-related reduction in blood DNA methylation at specific CpGs within the CXCL10
      gene promoter. In vitro analysis supported the role of DNA methylation in
      regulating CXCL10 transcription. A polymorphism (rs56061981) that altered
      methylation at one of these CpG sites further associated with working memory
      performance in 2 independent aging cohorts. Studying prefrontal cortex samples,
      we found higher CXCL10 protein levels in those with Alzheimer's disease, compared
      with aged controls. These findings support the association of peripheral
      inflammation, as demonstrated by CXCL10, in aging and cognitive decline. We
      reveal age-related epigenetic and genetic factors which contribute to the
      dysregulation of CXCL10.

PMID- 29223681
TI  - Language processing in age-related macular degeneration associated with unique
      functional connectivity signatures in the right hemisphere.
AB  - Age-related macular degeneration (AMD) is a retinal disease associated with
      significant vision loss among older adults. Previous large-scale behavioral
      studies indicate that people with AMD are at increased risk of cognitive deficits
      in language processing, particularly in verbal fluency tasks. The neural
      underpinnings of any relationship between AMD and higher cognitive functions,
      such as language processing, remain unclear. This study aims to address this
      issue using independent component analysis of spontaneous brain activity at rest.
      In 2 components associated with visual processing, we observed weaker functional
      connectivity in the primary visual cortex and lateral occipital cortex in AMD
      patients compared with healthy controls, indicating that AMD might lead to
      differences in the neural representation of vision. In a component related to
      language processing, we found that increasing connectivity within the right
      inferior frontal gyrus was associated with better verbal fluency performance
      across all older adults, and the verbal fluency effect was greater in AMD
      patients than controls in both right inferior frontal gyrus and right posterior
      temporal regions. As the behavioral performance of our patients is as good as
      that of controls, these findings suggest that preservation of verbal fluency
      performance in AMD patients might be achieved through higher contribution from
      right hemisphere regions in bilateral language networks. If that is the case,
      there may be an opportunity to promote cognitive resilience among seniors with
      AMD or other forms of late-life vision loss.

PMID- 29223683
TI  - A method to combine target volume data from 3D and 4D planned thoracic
      radiotherapy patient cohorts for machine learning applications.
AB  - BACKGROUND AND PURPOSE: The gross tumour volume (GTV) is predictive of clinical
      outcome and consequently features in many machine-learned models. 4D-planning,
      however, has prompted substitution of the GTV with the internal gross target
      volume (iGTV). We present and validate a method to synthesise GTV data from the
      iGTV, allowing the combination of 3D and 4D planned patient cohorts for
      modelling. MATERIAL AND METHODS: Expert delineations in 40 non-small cell lung
      cancer patients were used to develop linear fit and erosion methods to synthesise
      the GTV volume and shape. Quality was assessed using Dice Similarity Coefficients
      (DSC) and closest point measurements; by calculating dosimetric features; and by
      assessing the quality of random forest models built on patient populations with
      and without synthetic GTVs. RESULTS: Volume estimates were within the magnitudes
      of inter-observer delineation variability. Shape comparisons produced mean DSCs
      of 0.8817 and 0.8584 for upper and lower lobe cases, respectively. A model
      trained on combined true and synthetic data performed significantly better than
      models trained on GTV alone, or combined GTV and iGTV data. CONCLUSIONS: Accurate
      synthesis of GTV size from the iGTV permits the combination of lung cancer
      patient cohorts, facilitating machine learning applications in thoracic
      radiotherapy.

PMID- 29223684
TI  - Thromboelastometry as guidance for blood management in patients undergoing
      cardiac surgery.
AB  - OBJECTIVE: Thromboelastometry is a viscoelastometric method for haemostasis
      testing in a whole blood sample. The aim of this study was to assess the results
      of using thromboelastometry as guidance for blood management in cardiac surgery,
      postoperative adverse events and ICU stay. MATERIAL AND METHOD: Analytical and
      comparative non-randomised quasi-experimental prospective study with a
      retrospective control group. The inclusion criteria for the 80 patients were:
      patients undergoing cardiac surgery who had had prior cardiac surgery,
      endocarditis surgery or aortic arch surgery. Thirty-one patients were treated
      following routine transfusion practice during surgery (group A). The other 49
      patients were treated with thromboelastometrically guided transfusion algorithms
      (group B). The main objective was blood products transfused, and postoperative
      adverse events and ICU stay were the secondary objectives. RESULTS: Statistical
      analysis showed lower transfusion rates of fresh-frozen plasma in group B
      compared to group A (P<.001), as well as red blood cell transfusion during
      surgery with an average transfusion rate of 3.9 units in group A in comparison to
      2.67 units in group B (P=.125). Moreover, fibrinogen infusion was increased in
      group B compared to group A (P=.019). In addition, a lower rate of respiratory
      adverse events was found in group B (P=.019). There was a significant decrease in
      ICU stays over 7 days in group B compared to group A (P=.031). CONCLUSIONS: Using
      thromboelastometry guidance for blood management led to a meaningful reduction of
      fresh frozen plasma transfusion during surgery. This probably resulted in a
      reduction in respiratory adverse events after surgery and length of ICU stay in
      our patients.

PMID- 29223682
TI  - Neocortical origin and progression of gray matter atrophy in nonamnestic
      Alzheimer's disease.
AB  - Amnestic Alzheimer's disease (AD) is characterized by early atrophy of the
      hippocampus and medial temporal lobes before spreading to the neocortex. In
      contrast, nonamnestic Alzheimer's patients have relative sparing of the
      hippocampus, but the pattern in which the disease spreads is unclear. We examined
      spreading disease in nonamnestic AD using a novel magnetic resonance imaging
      based analysis adapted from pathologic staging studies, applied here to cross
      sectional imaging data. We selected 240 T1-weighted scans from 129 patients with
      pathology confirmed by autopsy or cerebrospinal fluid, and atrophy maps were
      computed relative to 238 scans from 115 elderly controls. For each phenotype, the
      frequency of atrophy in 116 brain regions was used to infer the anatomical origin
      of disease and its progression across 4 phases of atrophy. Results from the
      amnestic cohort were used to determine appropriate parameter settings for the
      phase assignment algorithm, based on correspondence to Braak pathology staging.
      Phase 1 regions, which represent the origin of disease, included the hippocampus
      for the amnestic group (comprising 33 scans); left lateral temporal lobe for
      logopenic-variant primary progressive aphasia (88 scans); occipitoparietal cortex
      for posterior cortical atrophy (51 scans); temporoparietal cortex for
      corticobasal syndrome (31 scans); and frontotemporal cortex for
      behavioral/dysexecutive variant AD (37 scans). In nonamnestic patients, atrophy
      spread to other neocortical areas in later phases, but the hippocampus exhibited
      only late-phase atrophy in posterior cortical atrophy and corticobasal syndrome.
      Region-specific phase values were also associated with regional measures of tau,
      beta amyloid, neuronal loss, and gliosis for the subset of patients (n = 17) with
      neuropathology findings; this comparison represented a first validation of the
      phase assignment algorithm. We subsequently assigned a phase to each patient scan
      based on the similarity of regional atrophy patterns with atrophy predicted for
      the corresponding phenotype at each phase. Scan-specific phases were correlated
      with disease duration as well as global and domain-specific cognition, supporting
      these phase values as global estimates of patients' disease progression. Logistic
      regression models based on spatial overlap with model-predicted atrophy patterns
      reliably discriminated nonamnestic phenotypes from each other and from amnestic
      AD. The frequency-based phase assignment algorithm used in the present study thus
      represents a promising approach for studying the neocortical origin and spread of
      disease in nonamnestic AD.

PMID- 29223685
TI  - The effect of partners' education on women's reproductive and maternal health in
      developing countries.
AB  - The effect of partners' education on women's and children's health in developing
      countries has received relatively little attention to date. This study uses
      couple data from 37 recent Demographic and Health Surveys fielded in sub-Saharan
      African and Asian countries to assess the effect of partners' schooling on
      women's modern contraceptive use, frequency of antenatal care visits, and skilled
      birth attendance. Using multilevel logistic regressions, the study shows that
      partners' schooling has strong effects on their spouses' maternal healthcare
      utilization; especially when partners had secondary or higher levels of
      schooling. Overall, women whose partners had an above secondary level of
      education were 32% more likely to use modern contraceptives, 43% more likely to
      attend at least four antenatal care visits, and 55% more likely to deliver their
      most recent baby with a health professional, compared to women whose partner had
      no education, after controlling for individual and community-level covariates.
      Finally, interacting the partners' years of schooling, we found that an
      additional year of partners' schooling was 1) positively associated with modern
      contraceptive use when the women had low educational attainment (substitution
      effect), but negatively associated when women were better educated, 2) positively
      and increasingly associated with the frequency of antenatal care visits as
      women's education increased (multiplicative effect), and 3) positively and
      significantly associated with skilled birth attendance for less educated women
      (substitution effect). This study highlights the importance of male education in
      shaping their wife's health behaviours in developing countries and provides
      strong impetus for male education beyond primary level (as well as for women),
      something that has been neglected in past policy discourse.

PMID- 29223686
TI  - Nourishing networks: A social-ecological analysis of a network intervention for
      improving household nutrition in Western Kenya.
AB  - RATIONALE: A growing body of research emphasizes the need to engage social
      networks in maternal and child nutrition interventions. However, an understanding
      of how interventions functionally engage not only mothers but fathers,
      grandparents, friends, and other social network members remains limited.
      OBJECTIVE: This study uses an adaptation of a social-ecological model to analyze
      the multiple levels at which the Kanyakla Nutrition Program operates to change
      behavior. METHODS: This study analyzes focus group data (four groups; n = 35, 7
      men and 28 women) following the implementation of the Kanyakla Nutrition Program,
      a novel nutrition intervention engaging social networks to increase nutrition
      knowledge, shift perceptions, and promote positive practices for infant and young
      child feeding and community nutrition in general. RESULTS: Participant
      perspectives indicate that the Kanyakla Nutrition Program contributed to
      nutrition knowledge and confidence, changed perceptions, and supported infant and
      child feeding practices at the individual, interpersonal, and institutional
      levels. However, many respondents report challenges in transcending barriers at
      the broader community and systems levels of influence, where environmental and
      economic constraints continue to affect food access. CONCLUSION: Analysis of the
      Kanyakla Nutrition Program suggests that for interventions addressing household
      level determinants of nutrition, simultaneously engaging the household's network
      of interpersonal and community relationships can play a role in building momentum
      and consensus to address persistent structural barriers to improved nutrition.

PMID- 29223687
TI  - Effect of control samples and listener attributes on speech naturalness ratings
      of people who stutter.
AB  - PURPOSE: Speech restructuring treatment can effectively reduce stuttering but the
      resultant speech may sound unnatural. Martin et al. (1984) speech naturalness
      scale is widely used by clinicians and researchers, yet little is known about
      whether including normally fluent speech samples alters the judgement of the
      naturalness of speech samples of people who stutter, and whether attributes of
      listeners - specifically training and sex - influence ratings. METHODS: In this
      study 20 untrained listeners (male and female) and 19 speech language pathology
      students (female only) rated either the naturalness of 21 speech samples from
      adults who stutter obtained post-treatment, or the same 21 post-treatment samples
      randomly mixed with samples of 21 samples from normally fluent speakers matched
      for age and sex. The independent variables were sample composition (addition of
      fluent controls) and listener training. The dependent variable was listener
      naturalness rating. RESULTS: A two-factor ANOVA with listener training and sample
      composition as independent variables and naturalness ratings as the dependent
      variable was performed. Untrained listeners rated samples as significantly less
      natural than trained listeners. The addition of control samples did not
      significantly impact scores assigned to post-treatment samples. A comparison of
      male and female listeners was completed using the Mann Whitney U Test. A
      significant group difference was observed with female listeners rating the
      samples more leniently (more natural) than male listeners. CONCLUSION: Based on
      this preliminary research, the addition of controls does not appear necessary in
      evaluating speech naturalness, however the composition of the listener group may
      affect results.

PMID- 29223688
TI  - Comparison of color flow with standard ultrasound for the detection of
      endotracheal intubation.
AB  - INTRODUCTION: Intubation is a frequently performed procedure in emergency
      medicine that is associated with significant morbidity and mortality when
      unrecognized esophageal intubation occurs. However, it may be difficult to
      visualize the endotracheal tube (ETT) in some patients. This study assessed
      whether the addition of color Doppler was able to improve the ability to
      visualize the ETT location. METHODS: This study was performed in a cadaver lab
      using three different cadavers chosen to represent varying neck circumference.
      Cadavers were randomized to tracheal or esophageal intubation. Blinded
      sonographers then assessed the location of the ETT using either grayscale or
      color Doppler imaging. Accuracy of sonographer identification of ETT location,
      time to identification, and operator confidence were assessed. RESULTS: One
      hundred and fifty intubations were performed and each was assessed by both
      standard and color Doppler techniques. There were 78 tracheal intubations and 72
      esophageal intubations. The standard technique was 99.3% (95% CI 96.3 to 99.9%)
      accurate. The color flow technique was also 99.3% (95% CI 96.3 to 99.9%)
      accurate. The mean operator time to identification was 3.24s (95% CI 2.97 to
      3.51s) in the standard approach and 5.75s (95% CI 5.16 to 6.33s) in the color
      flow technique. The mean operator confidence was 4.99/5.00 (95% CI 4.98 to 5.00)
      in the standard approach and 4.94/5.00 (95% CI 4.90 to 4.98) in the color flow
      technique. CONCLUSION: When added to standard ultrasound imaging, color flow did
      not improve accuracy or operator confidence for identifying ETT location and
      resulted in a longer examination time.

PMID- 29223689
TI  - Point-of-care hip ultrasound in a pediatric emergency department.

PMID- 29223690
TI  - Retrograde parotidectomy and facial nerve outcomes: A case series of 44 patients
      (Letter to Editor).

PMID- 29223691
TI  - Genome-wide association analysis of ear rot resistance caused by Fusarium
      verticillioides in maize.
AB  - The identification of causal regions associated with resistance to Fusarium
      verticillioides can be useful to understand resistance mechanisms and further be
      used in breeding programs. In this study, a genome-wide association study (GWAS)
      was conducted to identify candidate markers associated with resistance to the ear
      rot caused by the fungus F. verticillioides. A total of 242 maize inbred lines
      were genotyped with 23,153 DArT-seq markers. A total of 12 DArTs were associated
      with ear rot resistance. Some DArTs were localized close to genes with functions
      directly related to ear rot resistance, such as a gene responsible for the innate
      immune response that belongs to the class of NBS-LRR receptors. Some markers were
      also found to be closely associated with genes that synthesize transcription
      factors (nactf11 and nactf61), genes responsible for the oxidation-reduction
      process and peroxidase activity. These results are encouraging since some
      candidate markers can present functional relationship with ear rot resistance in
      maize.

PMID- 29223693
TI  - Atraumatic lumbar puncture needles: practice needs to change.

PMID- 29223692
TI  - Recent technological advancements in cardiac ultrasound imaging.
AB  - About 92.1 million Americans suffer from at least one type of cardiovascular
      disease. Worldwide, cardiovascular diseases are the number one cause of death
      (about 31% of all global deaths). Recent technological advancements in cardiac
      ultrasound imaging are expected to aid in the clinical diagnosis of many
      cardiovascular diseases. This article provides an overview of such recent
      technological advancements, specifically focusing on tissue Doppler imaging,
      strain imaging, contrast echocardiography, 3D echocardiography, point-of-care
      echocardiography, 3D volumetric flow assessments, and elastography. With these
      advancements ultrasound imaging is rapidly changing the domain of cardiac
      imaging. The advantages offered by ultrasound imaging include real-time imaging,
      imaging at patient bed-side, cost-effectiveness and ionizing-radiation-free
      imaging. Along with these advantages, the steps taken towards standardization of
      ultrasound based quantitative markers, reviewed here, will play a major role in
      addressing the healthcare burden associated with cardiovascular diseases.

PMID- 29223694
TI  - Atraumatic versus conventional lumbar puncture needles: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Atraumatic needles have been proposed to lower complication rates
      after lumbar puncture. However, several surveys indicate that clinical adoption
      of these needles remains poor. We did a systematic review and meta-analysis to
      compare patient outcomes after lumbar puncture with atraumatic needles and
      conventional needles. METHODS: In this systematic review and meta-analysis, we
      independently searched 13 databases with no language restrictions from inception
      to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic
      needles and conventional needles for any lumbar puncture indication. Randomised
      trials comparing atraumatic and conventional needles in which no dural puncture
      was done (epidural injections) or without a conventional needle control group
      were excluded. We screened studies and extracted data from published reports
      independently. The primary outcome of postdural-puncture headache incidence and
      additional safety and efficacy outcomes were assessed by random-effects and fixed
      effects meta-analysis. This study is registered with the International
      Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS: We
      identified 20 241 reports; after exclusions, 110 trials done between 1989 and
      2017 from 29 countries, including a total of 31 412 participants, were eligible
      for analysis. The incidence of postdural-puncture headache was significantly
      reduced from 11.0% (95% CI 9.1-13.3) in the conventional needle group to 4.2%
      (3.3-5.2) in the atraumatic group (relative risk 0.40, 95% CI 0.34-0.47,
      p<0.0001; I2=45.4%). Atraumatic needles were also associated with significant
      reductions in the need for intravenous fluid or controlled analgesia (0.44, 95%
      CI 0.29-0.64; p<0.0001), need for epidural blood patch (0.50, 0.33-0.75;
      p=0.001), any headache (0.50, 0.43-0.57; p<0.0001), mild headache (0.52, 0.38
      0.70; p<0.0001), severe headache (0.41, 0.28-0.59; p<0.0001), nerve root
      irritation (0.71, 0.54-0.92; p=0.011), and hearing disturbance (0.25, 0.11-0.60;
      p=0.002). Success of lumbar puncture on first attempt, failure rate, mean number
      of attempts, and the incidence of traumatic tap and backache did not differ
      significantly between the two needle groups. Prespecified subgroup analyses of
      postdural-puncture headache revealed no interactions between needle type and
      patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient
      position, indication for lumbar puncture, bed rest after puncture, or clinician
      specialty. These results were rated high-quality evidence as examined using the
      grading of recommendations assessment, development, and evaluation.
      INTERPRETATION: Among patients who had lumbar puncture, atraumatic needles were
      associated with a decrease in the incidence of postdural-puncture headache and in
      the need for patients to return to hospital for additional therapy, and had
      similar efficacy to conventional needles. These findings offer clinicians and
      stakeholders a comprehensive assessment and high-quality evidence for the safety
      and efficacy of atraumatic needles as a superior option for patients who require
      lumbar puncture. FUNDING: None.

PMID- 29223695
TI  - The Role of Space in Patients' Experience of an Emergency Department: A
      Qualitative Study.
AB  - INTRODUCTION: Nurses are increasingly involved in the design of health care
      facilities. Although their experience differs from that of patients, they are
      often expected to represent patients in design processes. Especially in the
      context of an emergency department, patients' states of mind alter their
      experiences. Knowledge about the role of space in ED patients' experience is
      limited. Our study aims to gain insight into this role and thus provide ED nurses
      with information to better represent ED patients' perspectives in design.
      METHODS: We conducted qualitative interviews with 22 patients. The interviews
      were supported by visual material collected through ethnographic methods to
      facilitate participants' reflections on the role of space in their experience.
      Participants were selected during their stays at the emergency department by
      convenience sampling. Interviews were audio-recorded, transcribed, and analyzed
      in combination with the visual material through open and axial coding. RESULTS:
      We found that the role of space in ED patients' experiences is affected by their
      altered sensory awareness and shaped by material, social, and time-related
      aspects. These aspects are intertwined and influenced by the transient character
      of the emergency department. DISCUSSION: The study indicates that paying
      attention to the role of space yields a nuanced understanding of ED patients'
      experiences. The challenge for hospital designers and staff lies in taking into
      account patients' altered sensory awareness and in designing interventions that
      support staff in emphasizing a human approach without counteracting the medical
      technical aspect of emergency care.

PMID- 29223696
TI  - Key Players in Key Roles: The Baystate Patient Progress Initiative to Improve
      Emergency Department Efficiency and Productivity.
AB  - BACKGROUND: The percentage of patients who leave the emergency department without
      being seen by a provider is a measure of efficiency and presents risk-management
      concerns. The number of patients actually "seen" by a provider is a measure of
      productivity. The opening of our new emergency department in December 2012,
      resulted in increases in both demand and the percentage of patients who left
      without being seen. Operational nursing leadership managed ED patient flow, but
      the structure was loosely organized on an ad hoc basis. METHODS: Operational
      nursing leadership roles were re-assigned to personnel with management aptitude
      and interest. The charge nurse coordinated care throughout all sections (pods) of
      the department while the pod lead nurse coordinated care in each pod. The flow
      coordinator nurse accepted transfers and emergency medical services arrivals.
      Nursing and physician staffing remained unchanged, and measures were calculated
      over a 3-year period (December 3, 2012, to December 2, 2015). The number of
      patients seen per day was analyzed using simple linear regression. The percentage
      of patients who left without being seen was analyzed using fractional logistic
      regression; P< 0.05 was considered statistically significant. RESULTS: The weekly
      mean number of patients seen per day rose 13% from 265 to 299 patients. The
      weekly mean percentage of patients who left without being seen declined 45% from
      8.2% to 4.5%. The regression lines for both measures were significant at P <
      0.001. CONCLUSION: Measures of efficiency and productivity can be improved
      significantly with a dedicated operational nursing leadership structure without
      adding nursing or physician staffing.

PMID- 29223697
TI  - A Case of Unilateral Endometriosis Coexisting with Struma Ovarii in Bilateral
      Ovarian Teratoma.

PMID- 29223698
TI  - Risk Factors for Unsuccessful Office-Based Endometrial Biopsy: A Comparative
      Study of Office-Based Endometrial Biopsy (Pipelle) and Diagnostic Dilation and
      Curettage.
AB  - STUDY OBJECTIVE: To determine the risk factors for Pipelle diagnostic failure,
      which might help healthcare providers choose the appropriate protocol for
      endometrial evaluation individually. DESIGN: A single-center prospective study
      (Canadian Task Force classification II). SETTING: The Obstetrics and Gynecology
      Hospital of Fudan University. PATIENTS: Patients (n = 466) with an indication for
      endometrial biopsy. INTERVENTIONS: All patients received Pipelle and then
      diagnostic dilation and curettage. The samples were sent for histopathologic
      diagnosis separately. MEASUREMENTS AND MAIN RESULTS: The Pipelle procedure failed
      in 10 of 466 patients (2.146%). The general sample inadequacy and histopathologic
      diagnosis inconsistency of Pipelle was 5.921% (27/456) and 14.254% (65/456),
      respectively. Upon multivariate analysis, history of cervical operation(s) (odds
      ratio [OR], 26.510; 95% coefficient interval [CI], 2.932-239.784; p = .004),
      prior intrauterine procedure(s) (OR, .096; 95% CI, .017-.554; p = .009), and
      pinpoint cervical os (OR, 5.939; 95% CI, 1.134-31.108; p = .035) were
      significantly associated with Pipelle procedure failure. Meanwhile, uterine
      volume < 43 cm3 (OR, 8.229; 95% CI, 1.902-35.601; p = .005) and uneven
      endometrium detected by ultrasound (OR, .176; 95% CI, .042-.734; p = .017) had
      significant correlation with sample inadequacy. Pipelle detected all endometrial
      cancer cases, whereas only 50.000% (7/14) of endometrial hyperplasia with atypia,
      26.471% (9/34) of polyps, and 18.182% (2/11) of polyps with endometrial
      hyperplasia without atypia cases were detected by Pipelle. CONCLUSION: Although
      Pipelle is the first-line method for endometrial biopsy, it might fail in women
      with risk factors identified in this study. More considerations should be taken
      when choosing Pipelle.

PMID- 29223699
TI  - Definitive Management of Persistent Vaginal Discharge Caused by Leiomyoma
      endometrial Fistulas after Uterine Artery Embolization.

PMID- 29223700
TI  - Unilateral sagittal split ramus osteotomy: an alternative for some cases of
      asymmetric mandibular prognathism.
AB  - The objective of this study was to propose a treatment protocol for patients with
      lateral prognathism based on the unilateral sagittal split ramus osteotomy
      (USSRO). This was a prospective study involving 31 patients with lateral
      prognathism, who required a bilateral sagittal split ramus osteotomy (BSSRO). Two
      groups were formed using the proposed protocol, with specific inclusion criteria
      for each group: BSSRO (n=17) and USSRO (n=14). Occlusal parameters (dental
      midline deviation, overbite, and overjet) were measured preoperatively (T0), at
      model surgery (T1), 1 month postoperative (T2), and 1year after surgery (T3) and
      compared. P-values of <0.05 were considered significant. No significant
      difference was found between the USSRO and BSSRO groups for all occlusal
      parameters (T0, T1, T2, and T3). In both groups, there was a significant
      difference between T0 and T1 and no significant difference between T1 and T2 or
      T1 and T3 in all of the occlusal parameters; the exception was overbite between
      T1 and T2 in the BSSRO group, which showed a significant difference. No patient
      in either group showed signs or symptoms of temporomandibular joint dysfunction
      at T0 or T3. USSRO was found to be a stable alternative in patients with
      asymmetric mandibular prognathism. At the same time, it reduced the operating
      time and morbidity when compared to BSSRO.

PMID- 29223701
TI  - Vector Flow Imaging Compared with Pulse Wave Doppler for Estimation of Peak
      Velocity in the Portal Vein.
AB  - The study described here investigated whether angle-independent vector flow
      imaging (VFI) technique estimates peak velocities in the portal vein comparably
      to pulsed wave Doppler (PWD). Furthermore, intra- and inter-observer agreement
      was assessed in a substudy. VFI and PWD peak velocities were estimated with from
      intercostal and subcostal views for 32 healthy volunteers, and precision analyses
      were conducted. Blinded to estimates, three physicians rescanned 10 volunteers
      for intra- and inter-observer agreement analyses. The precision of VFI and PWD
      was 18% and 28% from an intercostal view and 23% and 77% from a subcostal view,
      respectively. Bias between VFI and PWD was 0.57 cm/s (p = 0.38) with an
      intercostal view and 9.89 cm/s (p <0.001) with a subcostal view. Intra- and inter
      observer agreement was highest for VFI (inter-observer intra-class correlation
      coefficient: VFI 0.80, PWD 0.3; intra-observer intra-class correlation
      coefficient: VFI 0.90, PWD 0.69). Regardless of scan view, VFI was more precise
      than PWD.

PMID- 29223702
TI  - Rapid and highly efficient capture and release of cancer cells using polymeric
      microfibers immobilized with enzyme-cleavable peptides.
AB  - : Circulating tumor cells (CTCs) are tumor cells present in the blood. CTCs have
      attracted much attention as a new tumor marker, because their analysis provides
      useful information for monitoring cancer progress. In this study, we developed
      cell-capture and release methods using three-dimensional (3D) microfiber fabrics
      without damaging the cells. Using functional peptides containing sequences from a
      polystyrene-binding site and a cleavable site for collagenase type IV,
      immobilized antibodies on the peptides were able to specifically capture MCF-7
      cells in a few minutes and release the captured cells from 3D microfiber fabrics
      incorporating a vacuum system. The efficiency of cell capture was around 80% and
      that of the cell release was over 90%. The released cells proliferated normally
      in culture medium, suggesting that our system will be applicable for the culture
      and analysis of CTCs. STATEMENT OF SIGNIFICANCE: In this paper, we report cell
      capture and release methods using enzyme-cleavable peptides immobilized on
      microfiber fabrics which has microporous polymeric three-dimensional structures.
      Detachment and collection of the selectively captured cancer cells are required
      for ex vivo culture and their further analysis, whereas the cell detachment
      methods developed so far might cause cell damage, even if cell viability is high
      enough. Therefore, specific attachment and gentle detachment from the device are
      required for the accurate analysis of cells. In this study, for capture and
      release of cancer cells we designed the peptide cleavable by collagenase type IV,
      which has no target molecule in cells. Our system will be useful for further CTC
      analysis and might lead to more accurate cancer diagnosis.

PMID- 29223703
TI  - The foreign body response and morphometric changes associated with mesh-style
      peripheral nerve cuffs.
AB  - : Nerve cuffs have been used to anchor and protect penetrating electrodes in
      peripheral nerves and have been used as non-penetrating electrodes for neural
      recording and nerve stimulation. The material of choice for such applications is
      silicone, an inert synthetic biomaterial which elicits a minimal chronic foreign
      body response (FBR). While histological studies of solid silicone cuffs are
      available, to the best of our knowledge a comparison to other cuff designs is not
      well documented. Here, we describe the FBR and morphological changes that
      accompany nerve cuff implantation in the rat sciatic nerve by comparing a
      metallic mesh with and without a parylene coating to one made of silicone. Two
      months after implantation, we observed that such implants, irrespective of the
      cuff type, were associated with a persistent inflammatory response consisting of
      activated macrophages attached to the implant surfaces, which extended into the
      endoneurial space of the encapsulated nerve. We also observed foreign body giant
      cells in the epineurial space that were more prevalent in the mesh cohorts. The
      mesh cuff groups showed significant changes in several morphometric parameters
      that were not seen in the silicon group including reductions in nerve fiber
      packing density and a greater reduction of large diameter fibers. High
      magnification microscopy also showed greater evidence of foamy macrophages in the
      endoneurial space of the mesh implanted cohorts. Although the precise mechanisms
      are unknown, the results showed that mesh style nerve cuffs show a greater
      inflammatory response and had greater reductions in morphometric changes in the
      underlying nerve compared to silicone in the absence of a penetrating injury.
      STATEMENT OF SIGNIFICANCE: While traditional silicone cuffs have been in use for
      decades, the inflammatory and morphometric effects of these cuffs on the
      underlying nerve have not been deeply studied. Further, manipulation of the
      foreign body response to nerve cuffs by using various materials and/or designs
      has not been well reported. Therefore, we report the inflammatory response around
      nerve cuffs of various materials and designs, as well as report morphometric
      parameters of the underlying nerve. These data provide important information
      regarding the potential for quantitative morphometric changes associated with the
      use of nerve cuffs, and, importantly, suggests that these changes are associated
      with the degree of inflammation associated with the cuff.

PMID- 29223704
TI  - Decellularized heart ECM hydrogel using supercritical carbon dioxide for improved
      angiogenesis.
AB  - : Initial angiogenesis within the first 3 days is critical for healing ischemic
      diseases such as myocardial infarction. Recently, decellularized extracellular
      matrix (dECM) has been reported to provide tissue-derived ECM components and can
      be used as a scaffold for cell delivery for angiogenesis in tissue engineering.
      Decellularization by various detergents such as sodium dodecyl sulfate (SDS) and
      triton X-100 can remove the cell nuclei in tissue organs. However, this leads to
      ECM structure denaturation, decreased presence of various ECM proteins and
      cytokines, and loss of mechanical properties. To overcome these limitations, in
      this study, we developed a supercritical carbon dioxide and ethanol co-solvent
      (scCO2-EtOH) decellularization method, which is a detergent-free system that
      prevents ECM structure disruption and retains various angiogenic proteins in the
      heart dECM, and tested on rat heart tissues. The heart tissue was placed into the
      scCO2 reactor and decellularized at 37  degrees C and 350 bar. After scCO2-EtOH
      treatment, the effects were evaluated by DNA, collagen, and glycosaminoglycan
      (GAG) quantification and hematoxylin and eosin and immunofluorescence staining to
      determine the absence of nucleic acids and preservation of heart ECM components.
      Similar to the native group, the scCO2-EtOH group contained more ECM components
      such as collagen, GAGs, collagen I, laminin, and fibronectin and angiogenic
      factors including vascular endothelial growth factor, fibroblast growth factor,
      and platelet-derived growth factor and others in comparison to the detergent
      group. In addition, to estimate angiogenesis of the dECM hydrogels, the
      neutralized dECM solution was injected in a rat subcutaneous layer (n = 6 in each
      group: collagen, scCO2-EOH, and detergent group), after which the solution
      naturally formed gelation in the subcutaneous layer. After 3 days, the gels were
      harvested and estimated by immunofluorescence staining and the ImageJ program for
      angiogenesis analysis. Consequently, blood vessel formation and density of vWF
      and alpha-SMA in the scCO2-EtOH group were significantly greater than that in the
      collagen group. Here we suggest that heart-derived decellularized extracellular
      matrix (dECM) with scCO2-EtOH treatment is a highly promising angiogenic material
      for healing in ischemic disease. STATEMENT OF SIGNIFICANCE: Supercritical carbon
      dioxide (scCO2) in a supercritical phase has low viscosity and high diffusivity
      between gas and liquid properties and is known to be affordable, non-toxic, and
      eco-friendly. Therefore, scCO2 extraction technology has been extensively used in
      commercial and industrial fields. Recently, decellularized extracellular matrix
      (dECM) was applied to tissue engineering and regenerative medicine as a scaffold,
      therapeutic material, and bio-ink for 3D printing. Moreover, the general
      decellularization method using detergents has limitations including eliminating
      tissue-derived ECM components and disrupting their structures after
      decellularization. To overcome these limitations, heart tissues were treated with
      scCO2-EtOH for decellularization, resulting in preserving of tissue due to the
      various ECM and angiogenic factors derived. In addition, initiation of
      angiogenesis was highly induced even after 3 days of injection.

PMID- 29223705
TI  - Functional hepatocyte clusters on bioactive blend silk matrices towards
      generating bioartificial liver constructs.
AB  - : The creation of in vitro functional hepatic tissue simulating micro
      environmental niche of native liver is a keen area of research due to its demand
      in bioartificial liver (BAL) and cell-based tissue engineering. Here, we
      investigated the potential of novel blend (BA) silk scaffold fabricated by
      blending mulberry (Bombyx mori, BM) silk fibroin with cell adhesion motif (RGD)
      rich non-mulberry (Antheraea assamensis, AA) silk fibroin, in generating a
      functional liver construct. Three-dimensional (3D) porous silk scaffolds (BM, AA
      and BA) were physico-chemically characterized and functionally evaluated using
      human hepatocarcinoma cells (HepG2) and primary neonatal rat hepatocytes. The
      growth and distribution of hepatocytes within the scaffolds were tracked by
      FESEM, alamar blue proliferation assay and live/dead staining. Hemocompatible BA
      scaffolds supported the formation of high density hepatocyte clusters,
      facilitating cell-matrix and cell-cell interactions. Blend scaffolds evinced
      enhanced liver-specific functions of cultured hepatocytes in terms of albumin
      synthesis, urea synthesis and cytochrome P450 enzyme activity over 21 days.
      Subcutaneous implantation of scaffolds demonstrated minimal macrophage
      infiltration in blend scaffolds. These findings substantiate that the integral
      property of blend (BA) scaffold offers a befitting environment by influencing
      spheroidal growth of hepatocytes with enhanced biological activity. Collectively,
      the present study provides a new 3D bio-matrix niche for growing functional liver
      cells that would have future prospects in BAL as well as regenerative medicine.
      STATEMENT OF SIGNIFICANCE: An end stage liver disease called cirrhosis perturbs
      the self-healing ability and physiological functions of liver. Due to the
      scarcity of healthy donors, a functional in vitro hepatic construct retaining the
      liver-specific functions is in great demand for its prospects in bioartificial
      liver (BAL) and cell-based tissue engineering. Physicochemical attributes of a
      matrix influence the behavior of cultured hepatocytes in terms of attachment,
      morphology and functionality. Mulberry and non-mulberry silk fibroin presents
      unique amino acid sequence with difference in hydrophobicity and crystallinity.
      Considering this, the present study focuses on the development of a suitable
      three-dimensional (3D) bioactive matrix incorporating both mulberry silk fibroin
      and cell adhesion motif (RGD) rich non-mulberry silk fibroin. Porous silk blend
      scaffolds facilitated the formation of hepatocyte clusters with enhanced liver
      specific functions emphasizing both cell-cell and cell-matrix interactions.
      Hemocompatibility and integral property of blend scaffolds offers a biological
      niche for seeding functional liver cells that would have future prospects in
      biohybrid devices.

PMID- 29223707
TI  - Reliability of two techniques and training level of the observer in measuring the
      correction angle when planning a high tibial osteotomy.
AB  - BACKGROUND: In high tibial osteotomy, planning is critical for achieving
      successful realignment. Any method selected needs to be reliable, with inter
      observer and intra-observer correlation. A literature review demonstrated two
      distinct methods of planning for high tibial osteotomy. HYPOTHESIS: Both methods
      are precise and show excellent inter and intra-observer correlation. METHOD:
      Fifty consecutive weight-bearing long leg alignment antero-posterior (AP)
      radiographs were identified and planning undertaken on suitable radiographs using
      the methods of Puddu (method 1) and Miniaci (method 2). Two observers, one junior
      trainee and one Specialist Knee Fellow, recorded measurements to calculate inter
      and intra-observer correlation. RESULTS: Thirty-two radiographs were included.
      Inter-observer and intra-observer correlation, and correlation between the two
      methods were all greater than 0.97 (p<0.0001). CONCLUSION: Our results show
      excellent correlation between both methods and both observers. Both methods are
      reliable for planning and can be performed by both junior trainees and
      subspecialists. Further work should consider how planning can ensure adequate
      intraoperative correction.

PMID- 29223706
TI  - Cross-over clinical trial for evaluating the safety of camel's milk intake in
      patients who are allergic to cow's milk protein.
AB  - BACKGROUND: Cow's milk protein allergy (CMPA) affects between 0.6 and 0.9% of the
      general population, and its treatment implies the total elimination of the intake
      of this protein. Camel's milk has been suggested as an alternative for patients
      over one year of age who suffer from CMPA due to the difference in the amino acid
      sequence from that of cow's milk. The objective of this study was to evaluate the
      safety and tolerability of camel's milk in children with CMPA. METHODS: Crossed
      clinical trial for the use of camel's milk vs. amino acid formula, carried out at
      the Dr. Federico Gomez Children's Hospital of Mexico (HIMFG) on patients between
      one and 18 years of age with diagnosed CMPA confirmed through double-blind,
      placebo-controlled food challenges (DBPCFCs). Only those whose allergies were
      confirmed were randomly placed into two groups: those to be administered camel's
      milk and those to be administered the amino-acid formula for two weeks, followed
      by a six-week wash-out period, and then a group crossing for a further two weeks.
      RESULTS: 49 patients with suspected CMPA were included in the study; the
      diagnosis was confirmed through DBPCFCs in 15 patients, who were those who
      participated in the study. After having been administered camel's milk, none of
      the patients presented adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE:
      Camel's milk is safe and tolerable in patients above one year of age with CMPA
      and can be considered as a good alternative given the benefit of its taste
      compared to other formulas.

PMID- 29223708
TI  - Comparison of Neuroplastic Responses to Cathodal Transcranial Direct Current
      Stimulation and Continuous Theta Burst Stimulation in Subacute Stroke.
AB  - OBJECTIVE: To investigate the effects of cathodal transcranial direct current
      stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural
      network connectivity and motor recovery in individuals with subacute stroke.
      DESIGN: Double-blinded, randomized, placebo-controlled study. SETTING: University
      hospital rehabilitation unit. PARTICIPANTS: Inpatients with stroke (N=41; mean
      age, 65y; range, 28-85y; mean weeks poststroke, 5; range, 2-10) with resultant
      paresis in the upper extremity (mean Fugl-Meyer score, 14; range, 3-48).
      INTERVENTIONS: Subjects with stroke were randomly assigned to neuronavigated cTBS
      (n=14), cathodal tDCS (n=14), or sham transcranial magnetic stimulation/sham tDCS
      (n=13) over the contralesional primary motor cortex (M1). Each subject completed
      9 stimulation sessions over 3 weeks, combined with physical therapy. MAIN OUTCOME
      MEASURES: Brain function was assessed with directed and nondirected functional
      connectivity based on high-density electroencephalography before and after
      stimulation sessions. Primary clinical end point was the change in slope of the
      multifaceted motor score composed of the upper extremity Fugl-Meyer Assessment
      score, Box and Block test score, 9-Hole Peg Test score, and Jamar dynamometer
      results between the baseline period and the treatment time. RESULTS: Neither
      stimulation treatment enhanced clinical motor gains. Cathodal tDCS and cTBS
      induced different neural effects. Only cTBS was able to reduce transcallosal
      influences from the contralesional to the ipsilesional M1 during rest.
      Conversely, tDCS enhanced perilesional beta-band oscillation coherence compared
      with cTBS and sham groups. Correlation analyses indicated that the modulation of
      interhemispheric driving and perilesional beta-band connectivity were not
      independent mediators for functional recovery across all patients. However,
      exploratory subgroup analyses suggest that the enhancement of perilesional beta
      band connectivity through tDCS might have more robust clinical gains if started
      within the first 4 weeks after stroke. CONCLUSIONS: The inhibition of the
      contralesional M1 or the reduction of interhemispheric interactions was not
      clinically useful in the heterogeneous group of subjects with subacute stroke. An
      early modulation of perilesional oscillation coherence seems to be a more
      promising strategy for brain stimulation interventions.

PMID- 29223709
TI  - Bone Marrow Edema Syndrome of the Medial Femoral Condyle Treated With
      Extracorporeal Shock Wave Therapy: A Clinical and MRI Retrospective Comparative
      Study.
AB  - OBJECTIVE: To determine the validity of extracorporeal shock wave therapy (ESWT)
      in the treatment of bone marrow edema (BME) of the medial condyle of the knee.
      DESIGN: Retrospective. SETTING: Orthopedic Surgery outpatient clinic.
      PARTICIPANTS: Symptomatic patients (N=56) affected by BME of the medial condyle
      of the knee. Patients were equally divided into an ESWT-treated group and a
      control group, which was managed conservatively. INTERVENTIONS: ESWT delivery to
      the medial condyle of the affected knee. MAIN OUTCOME MEASURES: Clinical and
      functional assessment of the knee was performed with the use of the clinical and
      functional scores of the Knee Society Score (KSS). Pain was measured with the
      visual analog scale (VAS). BME area was measured with magnetic resonance imaging
      (MRI) before treatment and at 4 months' follow-up. RESULTS: Clinical evaluation
      of patients at final follow-up of 4 months posttreatment showed a significant
      improvement (P<.0001) of symptoms and knee functionality, both for range of
      motion and strength in both groups. VAS values were significantly improved
      (P<.0001) in both groups, with 3 patients in the ESWT group being pain-free
      (VAS=0) at 4 months' follow-up. At 4 months, MRI assessments on both sagittal and
      coronal views showed a significant reduction in BME in the ESWT group compared
      with the control group. CONCLUSIONS: Our findings show that ESWT is a valid
      nonpharmacologic and noninvasive therapy for spontaneous BME of the medial
      condyle that improves the affected vascular and metabolic state present in this
      pathologic disorder through its metabolic mechanisms of action.

PMID- 29223710
TI  - Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors
      and to a blood odor component.
AB  - The odor of blood may have both aversive and attractive properties for mammals,
      depending on the species of the odor donor and the species perceiving the odor.
      To better understand the informational content of blood odor for a prey species
      we assessed behavioral responses of male CD-1 mice (n=60) to the odor of blood of
      same-sex and opposite-sex conspecifics, of a natural predator of mice (cat), and
      of a herbivore (horse) and an omnivore (human) non-predator of mice. Further, we
      assessed their behavior towards the mammalian blood odor component trans-4,5
      epoxy-(E)-2-decenal which recent studies have shown to be as attractive to
      mammalian predators as the odor of real blood. A two-compartment test arena was
      used to record approach/avoidance behavior when the animals were presented with
      an odor in one compartment and a blank control in the other compartment. We found
      that both conspecific and heterospecific blood odors elicited significant
      avoidance behavior in the mice whereas a control odor (n-pentyl acetate) did not.
      The blood odor component trans-4,5-epoxy-(E)-2-decenal was also significantly
      avoided and thus appears to play an important role in the perception of mammalian
      blood odor in this prey species. These results support the notion that mammalian
      blood odor contains an olfactory warning signal which elicits an adaptive
      behavioral avoidance response in a prey species, the mouse. Our finding that the
      mice avoided the mammalian blood odor component trans-4,5-epoxy-(E)-2-decenal to
      the same degree as the odor of real blood suggests that this volatile compound
      might be (part of) this warning signal.

PMID- 29223712
TI  - Correlated colour temperature of morning light influences alertness and body
      temperature.
AB  - Though several studies have reported human alertness to be affected by the
      intensity and spectral composition of ambient light, the mechanism behind this
      effect is still largely unclear, especially for daytime exposure. Alerting
      effects of nocturnal light exposure are correlated with melatonin suppression,
      but melatonin levels are generally low during the day. The aim of this study was
      to explore the alerting effect of light in the morning for different correlated
      colour temperature (CCT) values, as well as its interaction with ambient
      temperature. Body temperature and perceived comfort were included in the study as
      possible mediating factors. In a randomized crossover design, 16 healthy females
      participated in two sessions, once under 2700K and once under 6500K light (both
      55lx). Each session consisted of a baseline, a cool, a neutral and a warm thermal
      environment. Alertness as measured in a reaction time task was lower for the
      6500K exposure, while subjective sleepiness was not affected by CCT. Also, core
      body temperature was higher under 6500K. Skin temperature parameters and
      perceived comfort were positively correlated with subjective sleepiness. Reaction
      time correlated with heat loss, but this association did not explain why the
      reaction time was improved for 2700K.

PMID- 29223711
TI  - An automated method to detect and quantify fungiform papillae in the human
      tongue: Validation and relationship to phenotypical differences in taste
      perception.
AB  - Determination of the number of fungiform papillae (FP) on the human tongue is an
      important measure that has frequently been associated with individual differences
      in oral perception, including taste sensitivity. At present, there is no
      standardised method consistently used to identify the number of FP, and primarily
      scientists manually count papillae over a small region(s) of the anterior tip of
      a stained tongue. In this study, a rapid automated method was developed to
      quantify the number of FP across the anterior 2cm of an unstained tongue from
      high resolution digital images. In 60 participants, the automated method was
      validated against traditional manual counting, and then used to assess the
      relationship between the number of FP and taste phenotype (both 6-n
      propylthiouracil (PROP) and Thermal Taster Status). FP count on the anterior 2cm
      of the tongue was found to correlate significantly with PROP taster status. PROP
      supertasters (PSTs) had a significantly higher FP count compared with PROP non
      tasters (PNTs). Conversely, the common approach used to determine the number of
      FP in a small 6mm diameter circle on the anterior tongue tip, did not show a
      significant correlation irrespective of whether it was determined via automated
      or manual counting. The regional distribution of FP was assessed across PROP
      taster status groups. PSTs had a significantly higher FP count within the first
      centimetre of the anterior tongue compared with the PNT and PROP medium-tasters
      (PMT), with no significant difference in the second centimetre. No significant
      relationship was found with Thermal Taster Status and FP count, or interaction
      with PROP taster status groups, supporting previous evidence suggesting these
      phenomena are independent. The automated method is a valuable tool, enabling
      reliable quantification of FP over the anterior 2cm surface of the tongue, and
      overcomes subjective discrepancies in manual counting.

PMID- 29223713
TI  - Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade
      and Low-grade Gliomas: A Comprehensive Meta-analysis.
AB  - RATIONALE AND OBJECTIVES: This study aimed to collect the studies on the role of
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic
      susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas,
      and evaluate the diagnostic performances of relevant quantitative parameters in
      glioma grading. MATERIALS AND METHODS: We systematically searched studies on the
      diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National
      Knowledge Infrastructure database, Cochrane Library, and Embase published between
      January 2005 and December 2016. Standardized mean differences and 95% confidence
      intervals were calculated for volume transfer coefficient (Ktrans), volume
      fraction of extravascular extracellular space (Ve), rate constant of backflux
      (Kep), relative cerebral blood volume (rCBV), and relative cerebral blood flow
      (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under
      the curve (AUC), and Begg test were calculated by Stata 12.0. RESULTS: Twenty-two
      studies with available outcome data were included in the analysis. The
      standardized mean difference of Ktrans values between high-grade glioma and low
      grade glioma were 1.18 (0.91, 1.45); Ve values were 1.43 (1.06, 1.80); Kep values
      were 0.65 (-0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were
      1.17 (0.68, 1.67), respectively. The results were all significant statistically
      (P < .05) except Kep values (P = .07), and high-grade glioma had higher Ktrans,
      Ve, rCBV, and rCBF values than low-grade glioma. AUC values of Ktrans, Ve, rCBV,
      and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC
      among the four parameters (P < .05). CONCLUSION: Both DCE-MRI and DSC-MRI are
      reliable techniques in differentiating the grades of gliomas, and rCBV was found
      to be the most sensitive one.

PMID- 29223714
TI  - Ayurveda: The future in the tradition.

PMID- 29223715
TI  - Development of two fluorine-18 labeled PET radioligands targeting PDE10A and in
      vivo PET evaluation in nonhuman primates.
AB  - INTRODUCTION: Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family
      that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP).
      Based on the successful development of [11C]T-773 as PDE10A positron emission
      tomography (PET) radioligand, in this study our aim was to develop and evaluate
      fluorine-18 analogs of [11C]T-773. METHODS: [18F]FM-T-773-d2 and [18F]FE-T-773-d4
      were synthesized from the same precursor used for 11C-labeling of T-773 in a two
      step approach via 18F-fluoromethylation and 18F-fluoroethylation, respectively,
      using corresponding deuterated synthons. A total of 12 PET measurements were
      performed in seven non-human primates. First, baseline PET measurements were
      performed using High Resolution Research Tomograph system with both [18F]FM-T-773
      d2 and [18F]FE-T-773-d4; the uptake in whole brain and separate brain regions, as
      well as the specific binding and tissue ratio between putamen and cerebellum, was
      examined. Second, baseline and pretreatment PET measurements using MP-10 as the
      blocker were performed for [18F]FM-T-773-d2 including arterial blood sampling
      with radiometabolite analysis in four NHPs. RESULTS: Both [18F]FM-T-773-d2 and
      [18F]FE-T-773-d4 were successfully radiolabeled with an average molar activity of
      293 +/- 114 GBq/MUmol (n=8) for [18F]FM-T-773-d2 and 209 +/- 26 GBq/MUmol (n=4)
      for [18F]FE-T-773-d4, and a radiochemical yield of 10% (EOB, n=12, range 3%-16%).
      Both radioligands displayed high brain uptake (~5.5% of injected radioactivity
      for [18F]FM-T-773-d2 and ~3.5% for [18F]FE-T-773-d4 at the peak) and a fast
      washout. Specific binding reached maximum within 30 min for [18F]FM-T-773-d2 and
      after approximately 45 min for [18F]FE-T-773-d4. [18F]FM-T-773-d2 data fitted
      well with kinetic compartment models. BPND values obtained indirectly through
      compartment models were correlated well with those obtained by SRTM. BPND
      calculated with SRTM was 1.0-1.7 in the putamen. The occupancy with 1.8 mg/kg of
      MP-10 was approximately 60%. CONCLUSIONS: [18F]FM-T-773-d2 and [18F]FE-T-773-d4
      were developed as fluorine-18 PET radioligands for PDE10A, with the [18F]FM-T-773
      d2 being the more promising PET radioligand warranting further evaluation.

PMID- 29223716
TI  - Alkaline degradation of lyophilized DMSA prior to labeling with 99mTc:
      Identification and development of the degradation pathway by HPLC and MS.
AB  - INTRODUCTION: Complexes of technetium-99m (99mTc) with meso-dimercaptosuccinic
      acid (DMSA) have been widely used as diagnostic agents in nuclear medicine. The
      degradation products (DP) of DMSA formed under different forced conditions have
      been identified through HPLC-DAD and LC-MSn studies. In this study, the DMSA kit
      was subjected to forced degradation under hydrolysis conditions as prescribed by
      the International Conference on Harmonization (ICH) guideline Q1A. METHODS:
      Chromatographic separation was accomplished on a reverse phase Shim-Pack VP-ODS
      (150 mm * 4.6 mm; 5 MUm) analytical column using the gradient elution method. LC
      MSn analysis was performed using an Esquire 3000 Plus ion trap mass spectrometer,
      operating under electrospray ionization (ESI). RESULTS: No products were found
      under acidic or neutral stress conditions. All the products found were identified
      through LC-MSn analyses and their fragmentation pathways were proposed. The DMSA
      standard degraded into an adduct DMSA dimer (2DMSA[-2H+Na]+) and adduct DMSA
      bound to fumaric acid and dithioglucolic acid (DTGA). In the DMSA kit, the
      degradation products were dimers and trimers of DMSA with tin. A possible
      degradation pathway is presented. CONCLUSIONS: This method proved to be
      convenient and effective since it provided fast and efficient separation of DMSA
      from its degradation products. The degradation studies carried out were able to
      delineate the stability of the DMSA standard and the DMSA kit.

PMID- 29223717
TI  - Synthesis and biological evaluation of novel synthetic chalcone derivatives as
      anti-tumor agents targeting Cat L and Cat K.
AB  - A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties
      were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and
      143B cell lines in vitro. SAR analysis showed that compounds bearing a
      benzenesulfonamide group had greater potency than those bearing a benzamide
      group. It was also shown that compounds with a mono-methyl or mono-halogen group
      at the 3-position on the terminal phenyl ring were more effective than those with
      trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti
      tumor activities against HCT116, MCF7 and 143B cell lines, with IC50 values of
      0.597, 0.886 and 0.791MUM, respectively. Molecular docking studies and enzymatic
      assays demonstrated that the anti-tumor activity of compound 8e might be
      regulated by Cat L and Cat K.

PMID- 29223718
TI  - Complete genome sequence of the highly Mn(II) tolerant Staphylococcus sp. AntiMn
      1 isolated from deep-sea sediment in the Clarion-Clipperton Zone.
AB  - Staphylococcus sp. AntiMn-1 is a deep-sea bacterium inhabiting seafloor sediment
      in the Clarion-Clipperton Zone (CCZ) that is highly tolerant to Mn(II) and
      displays efficient Mn(II) oxidation. Herein, we present the assembly and
      annotation of its genome.

PMID- 29223719
TI  - Physical Activity and Weight Loss Reduce the Risk of Breast Cancer: A Meta
      analysis of 139 Prospective and Retrospective Studies.
AB  - BACKGROUND: Physical activity and weight loss have been shown to reduce breast
      cancer incidence in numerous observational studies. The aim of this meta-analysis
      was to assess the effect of both physical activity and weight loss on breast
      cancer incidence. Specifically, we aimed to complete subgroup analyses by the
      intensity of physical activity and menopausal status at breast cancer diagnosis
      to further elucidate the relationship between physical activity, weight loss, and
      breast cancer incidence. MATERIALS AND METHODS: Studies were obtained from a
      database search of MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google
      Scholar through November 5, 2017. A random-effects model was used for pooled
      data. RESULTS: There were 139 studies included in the meta-analysis, including
      236,955 cases and 3,963,367 controls. Physical activity significantly reduced the
      risk of breast cancer (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.76
      0.81; P < .001), with high-intensity physical activity being slightly more
      protective (OR, 0.73; 95% CI, 0.65-0.81; P < .001) than low-intensity exercise
      (OR, 0.79; 95% CI, 0.72-0.86; P < .001). The effect size for general exercise was
      similar in both premenopausal (OR, 0.79; 95% CI, 0.73-0.87; P < .001) and
      postmenopausal (OR, 0.82; 95% CI, 0.78-0.86; P < .001) women. Additionally,
      weight loss reduced the risk of breast cancer incidence (OR, 0.82; 95% CI, 0.67
      0.97). CONCLUSION: Physical activity and weight loss significantly reduce the
      risk of breast cancer, irrespective of the timing and intensity of the exercise.

PMID- 29223720
TI  - Serum periostin is associated with body mass index and allergic rhinitis in
      healthy and asthmatic subjects.
AB  - BACKGROUND: Many studies have attempted to clarify the factors associated with
      serum periostin levels in asthmatic patients. However, these results were based
      on studies of subjects mainly characterized by high eosinophil counts, which may
      present as an obstacle for clarification in the identification of other factors
      associated with serum periostin levels. The aim of this study was to determine
      the factors associated with serum periostin levels in healthy subjects. We also
      assessed some factors in asthmatic subjects to confirm their extrapolation for
      management of asthma. METHODS: Serum periostin levels were measured in 230
      healthy subjects. Clinical factors of interest included body mass index (BMI) and
      allergic rhinitis (AR). Additionally, we confirmed whether these factors were
      associated with serum periostin in 206 asthmatic subjects. We further evaluated
      several obesity-related parameters, such as abdominal fat distribution and
      adipocytokine levels. RESULTS: Smoking status, blood eosinophil count, total
      immunoglobulin E, and the presence of AR were associated with serum periostin in
      healthy subjects. There was a negative association between BMI and serum
      periostin in both healthy and asthmatic subjects, while there was a tendency of a
      positive association with AR in asthmatic subjects. There were no differential
      associations observed for subcutaneous and abdominal fat in relation to serum
      periostin in asthmatic subjects. Serum periostin was significantly associated
      with serum levels of adiponectin, but not with leptin. CONCLUSIONS: Our results
      provided clarity as to the factors associated with serum periostin levels, which
      could be helpful in the interpretation of serum periostin levels in clinical
      practice.

PMID- 29223721
TI  - Dynamic Shunting Across a Patent Foramen Ovale in Adult Cardiac Surgery
      Perioperative Challenges and Management.

PMID- 29223722
TI  - The Effectiveness of Intravenous Parecoxib on the Incidence of Ipsilateral
      Shoulder Pain After Thoracotomy: A Randomized, Double-Blind, Placebo-Controlled
      Trial.
AB  - OBJECTIVES: To determine the incidence of ipsilateral shoulder pain (ISP) with
      the therapeutic use of parecoxib compared with a placebo after thoracotomy.
      DESIGN: A prospective, randomized, double-blind, placebo-controlled trial.
      SETTING: A tertiary-care university hospital. PARTICIPANTS: Adult patients
      undergoing an elective thoracotomy between June 2011 and February 2015.
      INTERVENTIONS: Patients were allocated randomly into the parecoxib group (n = 80)
      and the control group (n = 80). In the parecoxib group, 40 mg of parecoxib was
      diluted into 2 mL and given intravenously 30 minutes before surgery and then
      every 12 hours postoperatively for 48 hours. In the control group, 2 mL of normal
      saline was given to the patients at the same intervals. MEASUREMENTS AND MAIN
      RESULTS: A numerical rating scale was used to assess the intensity of ISP at 2,
      6, 12, 24, 48, 72, and 96 hours after surgery. Intravenous morphine (0.05 mg/kg)
      was used as the rescue medication for ISP during the 96-hour period. Baseline
      characteristics of patients in both groups were comparable. Patients in the
      parecoxib group had a significantly lower incidence of ISP, both overall (42.5% v
      62.0%, p = 0.014) and of moderate-to-severe ISP when compared with the control
      group (26.2% v 49.4%, p = 0.003). Parecoxib reduced the risk of ISP by a
      statistically significant 32% (risk ratio, 0.68; 95% confidence interval, 0.50
      0.93, p = 0.016). There were no significant differences in the occurrence of
      adverse effects between the groups. CONCLUSIONS: Intravenous parecoxib
      significantly can reduce the incidence and severity of ISP after thoracotomy.

PMID- 29223723
TI  - Aortic Regurgitation in Acute Type A Dissection.

PMID- 29223724
TI  - Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy.
AB  - Vasoplegic syndrome, characterized by low systemic vascular resistance and
      hypotension in the presence of normal or supranormal cardiac function, is a
      frequent complication of cardiovascular surgery. It is associated with a diffuse
      systemic inflammatory response and is mediated largely through cellular
      hyperpolarization, high levels of inducible nitric oxide, and a relative
      vasopressin deficiency. Cardiopulmonary bypass is a particularly strong
      precipitant of the vasoplegic syndrome, largely due to its association with
      nitric oxide production and severe vasopressin deficiency. Postoperative
      vasoplegic shock generally is managed with vasopressors, of which catecholamines
      are the traditional agents of choice. Norepinephrine is considered to be the
      first-line agent and may have a mortality benefit over other drugs. Recent
      investigations support the use of noncatecholamine vasopressors, vasopressin in
      particular, to restore vascular tone. Alternative agents, including methylene
      blue, hydroxocobalamin, corticosteroids, and angiotensin II, also are capable of
      restoring vascular tone and improving vasoplegia, but their effect on patient
      outcomes is unclear.

PMID- 29223725
TI  - Transfusion-associated circulatory overload: A survey among Dutch intensive care
      fellows.
AB  - OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a severe
      pulmonary transfusion reaction and leading cause of transfusion-related morbidity
      and mortality in Europe. TACO is of particular importance in critically ill
      patients, since they often receive blood transfusions and have multiple risk
      factors for TACO. This study investigates transfusion practices in patients at
      risk of developing TACO, and furthermore knowledge concerning risk factors,
      diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows.
      MATERIAL AND METHODS: An unannounced paper-based survey was conducted among Dutch
      ICU fellows during an educational conference. The survey consisted of 16 multiple
      and open choice questions. RESULTS: Of all 65 Dutch ICU fellows 56.8% completed
      the survey; of respondents 88.9% identified the correct constellation of symptoms
      for TACO. In total, 29.7% of the respondents are aware they are obligated to
      report TACO cases to the blood bank. Major risk factors for TACO that respondents
      identified were reduced left ventricular function, infusion volume and infusion
      rate. In a non-emergency setting, 45.9% of fellows start red blood cell
      transfusion with 2 units or more. Transfusion rates exceeded national guidelines
      in 15.4% of fictitious cases. TACO is treated with furosemide by 94.5% of the
      fellows, however goals of the therapy varied greatly. CONCLUSION: Dutch ICU
      fellows are knowledgeable of TACO symptoms, risk factors and treatment, however
      knowledge on reporting and transfusion practice in the setting of at risk
      patients for TACO should be improved.

PMID- 29223726
TI  - Computed tomography measurement of the left atrial appendage for optimal sizing
      of the Watchman device.
AB  - INTRODUCTION: Percutaneous left atrial appendage (LAA) occlusion is an emerging
      treatment option for patients with non-valvular atrial fibrillation who cannot
      tolerate oral anticoagulation. The Watchman device (Boston Scientific
      Corporation, Natick, MA, USA) is deployed at the ostium of the LAA, and an
      appropriately sized device is critical for successful occlusion. However,
      standardized imaging protocols for device sizing have not been established.
      OBJECTIVES: We investigated the clinical utility of a standardized imaging
      protocol, with pre-procedural multi-detector cardiac computed tomography (MDCT),
      and intra-procedural transesophageal echocardiography (TEE), for Watchman device
      sizing. METHODS: Patients who underwent Watchman device implantation between 2010
      and 2016 at our center, and who had pre-procedural MDCT and intra-procedural TEE
      were included. MDCT measurements (CTmax, CTmin, CTmean), and TEE measurement
      (TEEmax) of the LAA ostium were determined for each case, and correlated with the
      final size of the Watchman device implanted. Demographic data and clinical
      outcomes were collected. RESULTS: The study included 80 patients (mean age: 75 +/
      9.6 years; male: 68%; mean CHA2DS2-VASc score: 4.5 +/- 1.4). CTmax of the LAA
      ostium correlated strongly with the final deployed Watchman device size
      (Spearman's rho: 0.81, p < 0.001), while TEEmax of the LAA ostium showed only
      moderate correlation with the final deployed Watchman device size (Spearman's
      rho: 0.61, p < 0.001). Implantation success rate was 100%. At a mean duration of
      follow-up of 197 days, there were no device-related complications (device
      embolization, cardiac perforation and pericardial tamponade). At follow-up, the
      vast majority of patients (76 patients; 95%) had either no or trivial (<=3 mm)
      residual peri-device leak on TEE. CONCLUSIONS: A standardized imaging protocol
      for assessment of Watchman device implantation incorporating pre-procedural MDCT
      and intra-procedural TEE, was associated with excellent procedural outcomes at a
      mean duration of follow-up of 197 days.

PMID- 29223727
TI  - Urodynamic characteristics might be variable in bladder pain
      syndrome/interstitial cystitis patients with different non-bladder co-morbid
      conditions.
AB  - BACKGROUND: The aim of the study was to identify the impact of non-bladder co
      morbid conditions on the urodynamic characteristics of patients with bladder pain
      syndrome/interstitial cystitis. METHODS: Patients with bladder pain
      syndrome/interstitial cystitis completed the screening questionnaires for chronic
      fatigue syndrome, irritable bowel syndrome, fibromyalgia, temporo-mandibular
      disorders, multiple chemical sensitivities, tension/migraine headache, and
      localized myofascial pain disorder. They underwent either conventional pressure
      flow urodynamic studies or video-urodynamic studies. Urodynamic variables were
      compared between patients with and those without co-morbid conditions. RESULTS:
      Of 111 patients (16 males and 95 females) with bladder pain syndrome/interstitial
      cystitis, 87 (78.4%) had at least one co-morbid condition (62% males vs 82%
      females, p = 0.005). Those with concomitant irritable bowel syndrome were younger
      and had urodynamic characteristics of smaller catheter-free voided volume, lower
      catheter-free average flow rate, smaller bladder volume on the first desire to
      void, and more prevalent dysfunctional voiding than those without irritable bowel
      syndrome. Patients with concomitant localized myofascial pain disorder also had
      larger bladder volume at the first desire to void and lower pressure at maximum
      flow than those without co-morbid myofascial pain disorder. There were no
      significant differences in urodynamic parameters between bladder pain
      syndrome/interstitial cystitis patients with and those without other co
      morbidities. CONCLUSION: Bladder pain syndrome/interstitial cystitis patients,
      especially females, are more likely to have non-bladder co-morbidities,
      especially tension/migraine headache and localized myofascial pain. Bladder pain
      syndrome/interstitial cystitis Patients with co-morbid irritable bowel syndrome
      are younger and more likely to have abnormal urodynamic findings.

PMID- 29223728
TI  - Reply.

PMID- 29223729
TI  - Structure-Function Analysis of the C-Terminal Domain of the Type VI Secretion
      TssB Tail Sheath Subunit.
AB  - The type VI secretion system (T6SS) is a specialized macromolecular complex
      dedicated to the delivery of protein effectors into both eukaryotic and bacterial
      cells. The general mechanism of action of the T6SS is similar to the injection of
      DNA by contractile bacteriophages. The cytoplasmic portion of the T6SS is
      evolutionarily, structurally and functionally related to the phage tail complex.
      It is composed of an inner tube made of stacked Hcp hexameric rings, engulfed
      within a sheath and built on a baseplate. This sheath undergoes cycles of
      extension and contraction, and the current model proposes that the sheath
      contraction propels the inner tube toward the target cell for effector delivery.
      The sheath comprises two subunits: TssB and TssC that polymerize under an
      extended conformation. Here, we show that isolated TssB forms trimers, and we
      report the crystal structure of a C-terminal fragment of TssB. This fragment
      comprises a long helix followed by a helical hairpin that presents surface
      exposed charged residues. Site-directed mutagenesis coupled to functional assay
      further showed that these charges are required for proper assembly of the sheath.
      Positioning of these residues in the extended T6SS sheath structure suggests that
      they may mediate contacts with the baseplate.

PMID- 29223730
TI  - Characterization of a new decellularized bovine pericardial biological mesh:
      Structural and mechanical properties.
AB  - Implants made from naturally-derived biomaterials, also called biological meshes
      or biomeshes, typically derive from decellularized extracellular matrix of either
      animal or human tissue. Biomeshes have many biomedical applications such as
      ligament repair, bone and cartilage regeneration and soft tissue replacement.
      Bovine collagen is one of the most widely used and abundantly available xenogenic
      materials. In particular, bovine pericardium is widely used as extracellular
      matrix bioprosthetic tissue. The efficiency of a pericardial mesh to function as
      scaffold depends on the quality of the decellularization protocol used. Moreover,
      the biomesh mechanical features are critical for a successful surgical repair
      process, as they must reproduce the biological properties of the autologous
      tissue. Different methods of physical, chemical, or enzymatic decellularization
      exist, but no one has proved to be ideal. Therefore, in the present study, we
      developed a novel decellularization protocol for a bovine pericardium-derived
      biomesh. We characterized the biomesh obtained by comparing some ultrastructural,
      physical and mechanical features to a reference commercial biomesh.
      Quantification revealed that our novel decellularization process removed about
      90% of the native pericardial DNA. Microscopic and ultrastructural analysis
      documented the maintenance of the physiological structure of the pericardial
      collagen. Moreover, mechanical tests showed that both the extension and
      resilience of the new biomesh were statistically higher than the commercial
      control ones. The results presented in this study demonstrate that our protocol
      is promising in preparing high quality bovine pericardial biomeshes, encouraging
      further studies to validate its use in tissue engineering and regenerative
      medicine protocols.

PMID- 29223731
TI  - Permeability of expander breast implants: In vitro and in vivo analyses.
AB  - INTRODUCTION: The biocompatibility of the polysiloxane breast implant has been
      studied moderately. The aging of these implants due to lipid penetration and the
      release of polymerization impurities, such as Platine or
      octamethylcyclotetrasiloxane (named D4), has already been documented. Since these
      studies, manufacturing procedures have been improved; thus, the security of
      breast implants has also improved. Although polymerization and the choice of
      monomer influence the shell properties, few studies have compared these together
      in breast implants. Our study compares the permeability and mechanical resistance
      of 3 breast expander shells after in vivo and in vitro aging. RESULTS: In vitro,
      all tested shells quickly sorbed linear molecules, such as fatty acids, and
      released siloxane impurities. The penetration of a molecule with steric
      hindrance, such as cholesterol, is slower. Allergan shells have the highest rates
      of molecule sorption and siloxane release. In vivo, after implantation, Allergan
      shells lost their initial mechanical properties over time. This observation was
      not found for mentor shells. For all brands, many biological molecules penetrate
      the shells, among which cholesterol and fatty acids are always present.
      DISCUSSION: The aging of polysiloxane shells depends on the sorption of many
      biological molecules and the release of siloxane impurities. The siloxanes are
      impurities and / or degradation products that are due to aging. Moreover,
      according to our results, the shells act as matrices that separate molecules
      according to their chemical and physical properties. CONCLUSION: Not all
      polysiloxane expander shells have the same properties during aging. The
      manufacturing procedures and the choice of siloxane monomers are the two most
      probative factors that explain the observed differences.

PMID- 29223732
TI  - A comparison of 4D flow MRI-derived wall shear stress with computational fluid
      dynamics methods for intracranial aneurysms and carotid bifurcations - A review.
AB  - BACKGROUND: 4D flow MRI is a relatively quick method for obtaining wall shear
      stress (WSS) in vivo, a hemodynamic parameter which has shown promise in risk
      stratification for rupture of cerebrovascular diseases such as intracranial
      aneurysms and atherosclerotic plaques. The accuracy of such measurements is still
      largely unknown. OBJECTIVE: To quantify the accuracy of 4D flow MRI-derived wall
      shear stress values for intracranial aneurysms and carotid bifurcations. METHOD:
      We performed a review of all original research articles which compared the
      magnitudes of WSS derived from 4D flow MRI with corresponding values derived from
      computational fluid dynamics (CFD) within both intracranial aneurysms and carotid
      bifurcations. RESULT: For intracranial aneurysms and carotid bifurcations, 4D
      flow MRI-derived WSS estimations are generally lower in magnitude compared to WSS
      derived by CFD methods. These differences are more pronounced in regions of
      higher WSS. However, the relative distributions of WSS derived from both methods
      are reasonably similar. CONCLUSION: Pooled analysis suggests that WSS magnitudes
      obtained by 4D flow MRI are underestimated, while the relative distribution is
      reasonably accurate, the latter being an important factor for determining the
      natural history of intracranial aneurysms and other cerebrovascular diseases. 4D
      flow MRI shows enormous potential in providing new risk stratification parameters
      which could have significant impact on individualized treatment decisions and
      improved patient outcomes.

PMID- 29223733
TI  - Mitochondrial pore opening and loss of Ca2+ exchanger NCLX levels occur after
      frataxin depletion.
AB  - Frataxin-deficient neonatal rat cardiomyocytes and dorsal root ganglia neurons
      have been used as cell models of Friedreich ataxia. In previous work we show that
      frataxin depletion resulted in mitochondrial swelling and lipid droplet
      accumulation in cardiomyocytes, and compromised DRG neurons survival. Now, we
      show that these cells display reduced levels of the mitochondrial calcium
      transporter NCLX that can be restored by calcium-chelating agents and by external
      addition of frataxin fused to TAT peptide. Also, the transcription factor NFAT3,
      involved in cardiac hypertrophy and apoptosis, becomes activated by
      dephosphorylation in both cardiomyocytes and DRG neurons. In cardiomyocytes,
      frataxin depletion also results in mitochondrial permeability transition pore
      opening. Since the pore opening can be inhibited by cyclosporin A, we show that
      this treatment reduces lipid droplets and mitochondrial swelling in
      cardiomyocytes, restores DRG neuron survival and inhibits NFAT dephosphorylation.
      These results highlight the importance of calcium homeostasis and that targeting
      mitochondrial pore by repurposing cyclosporin A, could be envisaged as a new
      strategy to treat the disease.

PMID- 29223734
TI  - Activation of the EPOR-beta common receptor complex by cibinetide ameliorates
      impaired wound healing in mice with genetic diabetes.
AB  - Diabetes is characterized by poor wound healing which currently lacks an
      efficacious treatment. The innate repair receptor (IRR) is a master regulator of
      tissue protection and repair which is expressed as a response injury or metabolic
      stress, including in diabetes. Activation of the IRR might provide benefit for
      diabetic wound healing. A specific IRR agonist cibinetide was administered in an
      incisional wound healing model performed mice with genetic diabetes (db+/db+) and
      compared to the normal wild-type. Animals were treated daily with cibinetide
      (30MUg/kg/s.c.) or vehicle and euthanized 3, 7, and 14days after the injury to
      quantitate vascular endothelial growth factor (VEGF), malondialdehyde (MAL),
      phospho-Akt (pAkt), phospho e-NOS (p-eNOS), and nitrite/nitrate content within
      the wound. Additional evaluations included quantification of skin histological
      change, angiogenesis, scar strength, and time to complete wound closure.
      Throughout the wound healing process diabetic animals treated with vehicle
      exhibited increased wound MAL with reduced VEGF, pAkt, peNOS and nitrite/nitrate,
      all associated with poor re-epitheliziation, angiogenesis, and wound breaking
      strength. Cibenitide administration significantly improved these abnormalities.
      The results suggest that cibinetide-mediated IRR activation may represent an
      interesting strategy to treat diabetes-associated wound healing.

PMID- 29223736
TI  - Transepithelial transfer of phenanthrene, but not of benzo[a]pyrene, is inhibited
      by fatty acids in the proximal intestine of rainbow trout (Oncorhynchus mykiss).
AB  - The inclusion of vegetable oils in aquafeeds introduces contaminating polycyclic
      aromatic hydrocarbons (PAHs) in salmonids. Since lipophilic PAHs solubilize in
      micelles composed of lipids, bile salts and fatty acids, dietary lipid
      composition can alter intestinal transepithelial PAH transfer. We studied the
      uptake of two PAHs, viz. benzo[a]pyrene (BaP) and phenanthrene (PHE), in rainbow
      trout (Oncorhynchus mykiss) intestine. We also investigated the effects of two
      fatty acids, viz. fish oil-derived eicosapentaenoic acid (EPA, 20:5n-3) and
      vegetable oil-derived oleic acid (18:1n-9) on intestinal uptake. Radiolabeled
      PAHs were solubilized in micelles composed of tritiated EPA and oleic acid,
      respectively, and administrated to intestinal segments mounted in Ussing
      chambers. In the absence of micelles, PHE accumulation was two times higher than
      BaP in the mucosal and serosal layers of proximal and distal intestine.
      Administration of PHE in micelles composed of oleic acid resulted in a 50% lower
      accumulation of PHE in the mucosal layers of the proximal intestine compared to
      EPA-composed micelles. Accumulation of EPA and oleic acid in the proximal
      intestinal mucosa correlated negatively with the transepithelial transfer of
      these fatty acids across the proximal intestinal epithelium. Transepithelial PHE
      transfer across the proximal intestine was reduced by 30% in co-exposure with EPA
      composed micelles compared to 80% with oleic acid micelles. BaP was not
      transferred across the intestine. We conclude that the lipid composition of an
      aquafeed is an important determinant of PAH bioavailability. Therefore, lipid
      composition should be an important consideration in choosing vegetable oils as
      alternatives for fish oil in aquafeeds.

PMID- 29223735
TI  - Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis.
AB  - Liver fibrosis is overly exuberant wound healing that leads to portal
      hypertension or liver cirrhosis. Recent studies have demonstrated the functions
      of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting
      liver-specific BMP9 abnormalities will become an attractive approach for
      developing therapeutics to treat liver fibrosis. Here, we reveal that BMP9 serves
      as a valuable serum diagnostic indicator and efficient therapeutic target to
      attenuate liver fibrogenesis. Our analysis of biopsies from liver fibrotic
      patients revealed that higher BMP9 levels accompanied advanced stages of liver
      fibrosis. In mouse models, recombinant Bmp9 overexpression accelerated liver
      fibrosis, and adenovirus-mediated Bmp9 knockdown attenuated liver fibrogenesis.
      Intriguingly, BMP9 directly stimulated hepatic stellate cell activation via the
      SMAD signaling pathway to enhance hepatic fibrosis. Moreover, an inhibitory
      monoclonal antibody targeting Bmp9 was efficacious in treatment of mice with
      liver fibrosis. These observations delineate a novel model in which BMP9 directly
      drives SMAD/ID1 signaling in hepatic stellate cells, which modulates liver
      fibrogenesis development. Moreover, the findings unveil a promising surrogate
      biomarker for the diagnosis of hepatic fibrosis, thereby representing an
      efficient "BMP9 neutralization" approach in alleviating hepatic fibrosis.

PMID- 29223737
TI  - Synthesis and characterization of small-sized gold nanoparticles coated by bovine
      serum albumin (BSA) for cancer photothermal therapy.
AB  - In the present study, small gold nanoparticles <5 nm coated with natural protein
      Bovine Serum Albumin (BSA) was synthesized and characterized using UV-vis
      spectrophotometer, Dynamic Light Scattering (DLS), Transmission Electron
      Microscopy (TEM), zeta potential and scanning electron microscopy (SEM). Three
      types of cancer cell lines; Rhabdomyosarcoma (RD), Murine fibroblast (L20B) and
      RAW 264.7 monocyte-macrophage (MQ) were tested and treated by photothermal
      strategy, in vitro, by conjugating BSA-AuNPs complex of (0.125, 0.25, 0.5 and 1
      mg/ml) concentrations with continuous low power laser irradiation, green (532 nm)
      and near-infrared (NIR) (800 nm) at 0.5, 1, 2 and 3 min, separately. Cytotoxicity
      effect was determined by MTT assay. The vital impact of photothermal technique
      has investigated at 1 mg/ml and 3 min irradiation period as identified in RD cell
      line in comparison with other types; where cytotoxicity more than 74% was
      reached. Prominent results were demonstrated in the green and NIR region by pH 
      induced aggregation effect of small nanoparticles inside the cancer cells, which
      make the small-sized BSA-AuNPs are promising agents for cancer photothermal
      therapy.

PMID- 29223738
TI  - The applicability of fluorescence guided detection to epithelial dysplasia and
      oral cancer.

PMID- 29223740
TI  - Statistical models for brain signals with properties that evolve across trials.
AB  - Most neuroscience cognitive experiments involve repeated presentations of various
      stimuli across several minutes or a few hours. It has been observed that brain
      responses, even to the same stimulus, evolve over the course of the experiment.
      These changes in brain activation and connectivity are believed to be associated
      with learning and/or habituation. In this paper, we present two general
      approaches to modeling dynamic brain connectivity using electroencephalograms
      (EEGs) recorded across replicated trials in an experiment. The first approach is
      the Markovian regime-switching vector autoregressive model (MS-VAR) which treats
      EEGs as realizations of an underlying brain process that switches between
      different states both within a trial and across trials in the entire experiment.
      The second is the slowly evolutionary locally stationary process (SEv-LSP) which
      characterizes the observed EEGs as a mixture of oscillatory activities at various
      frequency bands. The SEv-LSP model captures the dynamic nature of the amplitudes
      of the band-oscillations and cross-correlations between them. The MS-VAR model is
      able to capture abrupt changes in the dynamics while the SEv-LSP directly gives
      interpretable results. Moreover, it is nonparametric and hence does not suffer
      from model misspecification. For both of these models, time-evolving connectivity
      metrics in the frequency domain are derived from the model parameters for both
      functional and effective connectivity. We illustrate these two models for
      estimating cross-trial connectivity in selective attention using EEG data from an
      oddball paradigm auditory experiment where the goal is to characterize the
      evolution of brain responses to target stimuli and to standard tones presented
      randomly throughout the entire experiment. The results suggest dynamic changes in
      connectivity patterns over trials with inter-subject variability.

PMID- 29223739
TI  - Domain-general and domain-specific neural changes underlying visual expertise.
AB  - Visual expertise induces changes in neural processing for many different domains
      of expertise. However, it is unclear how expertise effects for different domains
      of expertise are related. In the present fMRI study, we combine large-scale
      univariate and multi-voxel analyses to contrast the expertise-related neural
      changes associated with two different domains of expertise, bird expertise
      (ornithology) and mineral expertise (mineralogy). Results indicated distributed
      expertise-related neural changes, with effects for both domains of expertise in
      high-level visual cortex and effects for bird expertise even extending to low
      level visual regions and the frontal lobe. Importantly, a multivariate
      generalization analysis showed that effects in high-level visual cortex were
      specific to the domain of expertise. In contrast, the neural changes in the
      frontal lobe relating to expertise showed significant generalization, signaling
      the presence of domain-independent expertise effects. In conclusion, expertise is
      related to a combination of domain-specific and domain-general changes in neural
      processing.

PMID- 29223741
TI  - Predict, then simplify.
AB  - The desire to understand a given phenomenon is at the core of a scientist's
      mission. Yet what is meant by "understanding"? As soon as we try to
      operationalize this concept, I argue that understanding amounts to building
      models of a set of related empirical phenomena. In this commentary, I discuss
      three such criteria, namely, predictability, simplicity, and computability, that
      I find useful in guiding the quest for better models and what they imply for the
      use of deep nets in brain research.

PMID- 29223742
TI  - Network analysis reveals disrupted functional brain circuitry in drug-naive
      social anxiety disorder.
AB  - Social anxiety disorder (SAD) is a common and disabling condition characterized
      by excessive fear and avoidance of public scrutiny. Psychoradiology studies have
      suggested that the emotional and behavior deficits in SAD are associated with
      abnormalities in regional brain function and functional connectivity. However,
      little is known about whether intrinsic functional brain networks in patients
      with SAD are topologically disrupted. Here, we collected resting-state fMRI data
      from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed
      functional networks with 34 predefined regions based on previous meta-analytic
      research with task-based fMRI in SAD, and performed network-based statistic and
      graph-theory analyses. The network-based statistic analysis revealed a single
      connected abnormal circuitry including the frontolimbic circuit (termed the "fear
      circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal
      cortex and insula) and posterior cingulate/occipital areas supporting perceptual
      processing. In this single altered network, patients with SAD had higher
      functional connectivity than HC. At the global level, graph-theory analysis
      revealed that the patients exhibited a lower normalized characteristic path
      length than HC, which suggests a disorder-related shift of network topology
      toward randomized configurations. SAD-related deficits in nodal degree,
      efficiency and participation coefficient were detected in the parahippocampal
      gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the
      calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety
      symptoms. These findings highlight the aberrant topological organization of
      functional brain network organization in SAD, which provides insights into the
      neural mechanisms underlying excessive fear and avoidance of social interactions
      in patients with debilitating social anxiety.

PMID- 29223743
TI  - Early vs. late tracheostomy in intensive care settings: Impact on ICU and
      hospital costs.
AB  - INTRODUCTION: Up to 12% of the 800,000 patients who undergo mechanical
      ventilation in the United States every year require tracheostomies. A recent
      systematic review showed that early tracheostomy was associated with better
      outcomes: more ventilator-free days, shorter ICU stays, less sedation and reduced
      long-term mortality. However, the financial impact of early tracheostomies remain
      unknown. OBJECTIVES: To conduct a cost-analysis on the timing of tracheostomy in
      mechanically ventilated patients. METHODS: We extracted individual length of
      hospital stay and length of ICU stay data from the studies included in the
      systematic review from Hosokawa et al. We also searched for any recent randomized
      control trials on the topic that were published after this review. The weighted
      length of stay was estimated using a random effects model. Average daily hospital
      and ICU costs per patients were obtained from a cost study by Kahn et al. We
      estimated hospital and ICU costs by multiplying LOS with respective average daily
      cost per patient. We calculated difference in costs by subtracting hospital
      costs, ICU costs and total direct variable costs from early tracheotomy to late
      tracheotomy. 95% confidence intervals were estimated using bootstrap re-sampling
      procedures with 1000 iterations. RESULTS: The average weighted cost of ICU stay
      in patients with an early tracheostomy was $4316 less when compared to patients
      with late tracheostomy (95% CI: 403-8229). Subgroup analysis revealed that very
      early tracheostomies (<4days) cost on average $3672 USD less than late
      tracheostomies (95% CI: -1309, 10,294) and that early tracheostomies (<10days but
      >4) cost on average $6385 USD less than late tracheostomies (95% CI: -4396
      17,165). CONCLUSION: This study shows that early tracheostomy can significantly
      reduce direct variable and likely total hospital costs in the intensive care unit
      based on length of stay alone. This is in addition to the already shown benefits
      of early tracheostomy in terms of ventilator dependent days, reduced length of
      stays, decreased pain, and improved communication. Further prospective studies on
      this topic are needed to prove the cost-effectiveness of early tracheostomy in
      the critically ill population.

PMID- 29223744
TI  - Effect of various antipsychotic regimens on incidence of delirium in critically
      ill adults.
AB  - PURPOSE: Delirium is common during critical illness but it is unknown whether the
      choice of antipsychotic or dosing strategy impacts delirium outcomes. We
      evaluated the incidence of delirium in critically ill adults receiving different
      antipsychotic regimens. MATERIALS AND METHODS: Single center retrospective cohort
      study of adult patients admitted to the intensive care unit (ICU). Patients who
      received haloperidol or quetiapine and scored negative on the Confusion
      Assessment Method for the ICU (CAM-ICU) prior to initiation were included.
      Patients were divided into four groups based on dosing schedule of the
      antipsychotic. The primary outcomes were the incidence and duration of delirium.
      RESULTS: Eighty patients were included in the study. Patients received scheduled
      quetiapine (35%), PRN haloperidol (55%), and PRN quetiapine (10%). The overall
      incidence of delirium in patients receiving antipsychotics was 39%. The incidence
      of delirium was similar between the scheduled quetiapine group, PRN haloperidol
      and PRN quetiapine groups, at 39%, 50% and 36%, respectively (p=0.79). The
      scheduled quetiapine group had a longer time to first episode of delirium, but
      this was not statistically significant (11days vs 4.8days vs 5.6days; p=0.20).
      CONCLUSIONS: There was no difference in incidence or duration of delirium between
      quetiapine and haloperidol regimens.

PMID- 29223746
TI  - BCAP promotes osteoclast differentiation through regulation of the p38-dependent
      CREB signaling pathway.
AB  - Many studies have determined that PI3K-Akt signaling pathways play important
      roles in osteoclast differentiation and function. In the present study, we
      investigated the roles of B-cell adaptor for PI3K (BCAP), which is a PI3K binding
      molecule, in osteoclasts. Overexpression of BCAP in osteoclast precursor cells
      enhanced osteoclast differentiation induced by tumor necrosis factor alpha (TNF
      alpha) as well as receptor activator of nuclear factor-kappaB ligand (RANKL).
      Conversely, osteoclast differentiation mediated by both cytokines was attenuated
      when BCAP expression was downregulated using small interfering RNA. Notably, BCAP
      induced Akt activation only upon stimulation by RANKL, but not by TNF-alpha.
      However, BCAP activated p38-dependent cAMP response element-binding protein
      (CREB) phosphorylation induced by both RANKL and TNF-alpha. Collectively, we
      showed that BCAP plays an important role in osteoclast differentiation by
      regulating the p38-dependent CREB signaling pathway, and that BCAP might be a new
      therapeutic target for bone diseases.

PMID- 29223745
TI  - Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor
      positive, HER2-negative, advanced breast cancer progressing on or after mTOR
      inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3
      trial.
AB  - BACKGROUND: Activation of the PI3K/AKT/mTOR pathway occurs frequently in breast
      cancer that is resistant to endocrine therapy. Approved mTOR inhibitors
      effectively inhibit cell growth and proliferation but elicit AKT phosphorylation
      via a feedback activation pathway, potentially leading to resistance to mTOR
      inhibitors. We evaluated the efficacy and safety of buparlisib plus fulvestrant
      in patients with advanced breast cancer who were pretreated with endocrine
      therapy and mTOR inhibitors. METHODS: BELLE-3 was a randomised, double-blind,
      placebo-controlled, multicentre, phase 3 study. Postmenopausal women aged 18
      years or older with histologically or cytologically confirmed hormone-receptor
      positive, HER2-negative, locally advanced or metastatic breast cancer, who had
      relapsed on or after endocrine therapy and mTOR inhibitors, were recruited from
      200 trial centres in 22 countries. Eligible patients were randomly assigned (2:1)
      via interactive response technology (block size of six) to receive oral
      buparlisib (100 mg per day) or matching placebo starting on day 1 of cycle 1,
      plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1 and on day 1
      of subsequent 28-day cycles. Randomisation was stratified by visceral disease
      status. The primary endpoint was progression-free survival by local investigator
      assessment as per the Response Evaluation Criteria In Solid Tumors (RECIST)
      version 1.1 in the full analysis population (all randomised patients, by
      intention-to-treat). Safety was analysed in all patients who received at least
      one dose of treatment and at least one post-baseline safety assessment. This
      study is registered with ClinicalTrials.gov, number NCT01633060, and is ongoing
      but no longer enrolling patients. FINDINGS: Between Jan 15, 2013, and March 31,
      2016, 432 patients were randomly assigned to the buparlisib (n=289) or placebo
      (n=143) groups. Median progression-free survival was significantly longer in the
      buparlisib versus placebo group (3.9 months [95% CI 2.8-4.2] vs 1.8 months [1.5
      2.8]; hazard ratio [HR] 0.67, 95% CI 0.53-0.84, one-sided p=0.00030). The most
      frequent grade 3-4 adverse events in the buparlisib versus placebo group were
      elevated alanine aminotransferase (63 [22%] of 288 patients vs four [3%] of 140),
      elevated aspartate aminotransferase (51 [18%] vs four [3%]), hyperglycaemia (35
      [12%] vs none), hypertension (16 [6%] vs six [4%]), and fatigue (ten [3%] vs two
      [1%]). Serious adverse events were reported in 64 (22%) of 288 patients in the
      buparlisib group versus 23 (16%) of 140 in the placebo group; the most frequent
      serious adverse events (affecting >=2% of patients) were elevated aspartate
      aminotransferase (six [2%] vs none), dyspnoea (six [2%] vs one [1%]), and pleural
      effusion (six [2%] vs none). On-treatment deaths occurred in ten (3%) of 288
      patients in the buparlisib group and in six (4%) of 140 in the placebo group;
      most deaths were due to metastatic breast cancer, and two were considered
      treatment-related (cardiac failure [n=1] in the buparlisib group and unknown
      reason [n=1] in the placebo group). INTERPRETATION: The safety profile of
      buparlisib plus fulvestrant does not support its further development in this
      setting. Nonetheless, the efficacy of buparlisib supports the rationale for the
      use of PI3K inhibitors plus endocrine therapy in patients with PIK3CA mutations.
      FUNDING: Novartis Pharmaceuticals Corporation.

PMID- 29223747
TI  - An automated high-throughput system for phenotypic screening of chemical
      libraries on C. elegans and parasitic nematodes.
AB  - Parasitic nematodes infect hundreds of millions of people and farmed livestock.
      Further, plant parasitic nematodes result in major crop damage. The pipeline of
      therapeutic compounds is limited and parasite resistance to the existing
      anthelmintic compounds is a global threat. We have developed an INVertebrate
      Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical
      screening, and an algorithm (Paragon) which allows screening for compounds that
      have an effect on motility and development of parasitic worms. We have validated
      its utility by determining the efficacy of a panel of known anthelmintics against
      model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus,
      Teladorsagia circumcincta, and Trichuris muris. We then applied the system to
      screen the Pathogen Box chemical library in a blinded fashion and identified
      compounds already known to have anthelmintic or anti-parasitic activity,
      including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously
      undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes.
      This system offers an effective, high-throughput system for the discovery of
      novel anthelmintics.

PMID- 29223749
TI  - No. 356-Egg Freezing for Age-Related Fertility Decline.
AB  - OBJECTIVE: To provide a comprehensive review and evidence based recommendations
      for Canadian fertility centres that offer social egg freezing. OUTCOMES: In
      social egg freezing cycles we evaluated thawed oocyte survival rates,
      fertilization rates, embryo quality, pregnancy rates, and live birth rates. We
      also review how these outcomes are impacted by age, ovarian reserve, and the
      number of eggs cryopreserved. Finally, we discuss the risks of social egg
      freezing, the alternatives, the critical elements for counselling and informed
      consent, and future reporting of egg freezing outcome data. EVIDENCE: Published
      literature was reviewed through searches of MEDLINE and CINAHL using appropriate
      vocabulary and using key words ("oocyte cryopreservation," "egg freezing," "egg
      vitrification," "social egg freezing," and "elective egg freezing"). Results
      included systematic reviews, randomized controlled trials, controlled clinical
      trials, and observational studies. Expert opinion based on clinical experience,
      descriptive studies, or reports of expert committees was also included to discuss
      aspects of egg freezing not currently rigorously studied. VALUES: The evidence
      obtained was reviewed and evaluated by the Clinical Practice Guideline (CPG)
      Committees of the Canadian Fertility and Andrology Society (CFAS) under the
      leadership of the principal authors. BENEFITS, HARMS, AND COSTS: Implementation
      of this guideline should assist the clinician to develop an optimal approach in
      providing counselling for egg freezing while minimizing harm and improving
      patient outcomes during treatment. VALIDATION: These guidelines have been
      reviewed and approved by the membership of the CFAS and by the CPG Committees of
      CFAS and The Society of Obstetricians and Gynaecologists of Canada (SOGC).
      SPONSORS: CFAS and SOGC. RECOMMENDATIONS: 

PMID- 29223748
TI  - Is tricuspid annuloplasty increasing surgical mortality and morbidity during
      mitral valve replacement? A single-centre experience.
AB  - BACKGROUND: Performance of tricuspid annuloplasty (TA) in patients undergoing
      mitral valve surgery is recommended based on the degree of tricuspid
      regurgitation and tricuspid annulus size, but is often underused. AIM: To
      evaluate the impact of combined TA on in-hospital outcome in patients undergoing
      mitral valve replacement (MVR). METHODS: We selected all consecutive patients who
      underwent MVR for native valve disease. Clinical, echocardiographic and in
      hospital complications were obtained from chart review. RESULTS: We identified
      287 patients (mean age 62+/-17 years; 44% men). Combined TA was performed in 165
      patients (57%), who had more rheumatic disease (71% vs. 24%; P<0.0001) and mitral
      stenosis (55% vs. 22%; P<0.0001), but less endocarditis (4% vs. 31%; P<0.0001),
      were more often in atrial fibrillation (54% vs. 22%; P<0.0001), were more
      severely symptomatic (80% vs. 57%; P<0.0001), presented with a higher systolic
      pulmonary artery pressure (SPAP) (53+/-16 vs. 45+/-15mmHg; P=0.0002) and were
      less likely to have required emergency surgery (17% vs. 38%; P<0.0001). Despite
      this higher risk profile, in-hospital mortality was slightly lower (5% vs. 13%;
      P=0.02) and complication rates were similar (redo surgery 22% vs. 16% [P=0.18]
      and tamponade 20% vs. 15% [P=0.15]). After adjustment for age, sex, functional
      class, SPAP, emergency surgery and concomitant coronary artery bypass graft or
      aortic valve replacement surgery, combined TA was not associated with an
      increased rate of in-hospital death (P=0.08) or major complications (P=0.89).
      CONCLUSIONS: In a consecutive series of patients who underwent MVR, TA did not
      seem to have a negative impact on immediate outcome. Hence, additional
      performance of TA at the time of MVR should not be declined on the basis of an
      increased surgical risk.

PMID- 29223750
TI  - Choosing Pre-conception Planning for Women/Families: Counselling and Informed
      Consent (Part 2) - Pre-conception Reproductive Planning, Lifestyle, Immunization,
      and Psychosocial Issues.
AB  - OBJECTIVE: To inform reproductive and other health care providers about pre
      conception evaluation, including considerations for reproductive planning,
      lifestyle modification, immunization status and attitudes, and psychosocial
      issues. OPTIONS: This counselling information can be used for patient education
      and planning and possible pre-conception and/or prenatal testing. OUTCOMES: This
      information may allow for improved risk assessment when pre-conception
      counselling for individual patients and their families is used. CONSIDERATIONS
      FOR PRE-CONCEPTION CARE (PART 2) REGARDING PRE-CONCEPTION REPRODUCTIVE PLANNING,
      LIFESTYLE, IMMUNIZATIONS, AND PSYCHOSOCIAL ISSUES: CONSIDERATION FOR CARE
      STATEMENTS: For this review article, the Consideration for Care Statements use
      the Grading of Recommendations, Assessment, Development and Evaluations strength
      and quality principles because they are comparable for the clinician and the
      patient/public user. For example, "Strong" for clinicians is defined as "the
      recommendation would apply to most individuals. Formal discussion aids are not
      likely to be needed to help individuals make decisions consistent with their
      values and preferences." For patients/the public, "Strong" is defined as, "we
      believe most people in this situation would want the recommended course of
      actions and only a small number would not." Quality of evidence (High, Moderate,
      Low) is based on the confidence that the true effect lies close to that of the
      estimate of the effect. In addition, the Canadian Task Force on Preventive Health
      Care key to evidence statements and grading of recommendations are included.
      EVIDENCE: PubMed, Medline, and the Cochrane Database were searched until May
      2017, using appropriate key words (i.e., preconception, reproductive planning,
      lifestyle modification, immunization risks and benefits, psychosocial pregnancy
      factors/issues). Grey (unpublished) literature was identified through searching
      websites of health technology assessment and health technology assessment-related
      agencies, clinical practice guideline collections, and national and international
      medical specialty societies. BENEFITS, HARMS, AND COSTS: The benefits for the
      patient and her family from receiving this pre-conception counseling would
      include an increased understanding of the relevant issues for both pre-conception
      and in early pregnancy as well as better pregnancy outcomes. Harm includes
      potential increased anxiety or psychological stress associated with the
      possibility of identifying maternal pregnancy risks.

PMID- 29223751
TI  - Preparation, deproteinization, characterisation, and antioxidant activity of
      polysaccharide from cucumber (Cucumis saticus L.).
AB  - Preparation, deproteinization and antioxidant activity of polysaccharide from
      cucumber (Cucumis saticus L.) were investigated. The crude cucumber
      polysaccharide was extracted by hydrothermal method. It showed that the
      trichloroacetic acid (TCA) method had the higher deproteinization percentage, but
      a little higher polysaccharide loss percentage than the CaCl2 method. The
      cucumber polysaccharide is linked by the beta-glycosidic linkage. It consisted of
      d-glucose, d-mannose, d-galactose, l-rhamnose, d-xylose, l-arabinose, d
      glucuronic acid, and d-galacturonic acid. Their mole ratio was
      6.00:4.03:8.31:2.82:2.75:6.60:1.05:5.79. Moreover, it proved that the cucumber
      polysaccharide had high scavenging ability to superoxide anions.

PMID- 29223752
TI  - A novel low molecular weight Enteromorpha polysaccharide-iron (III) complex and
      its effect on rats with iron deficiency anemia (IDA).
AB  - Iron deficiency anemia (IDA) is a common nutritional disease that affects normal
      erythropoiesis. Traditional iron supplements usually cause gastrointestinal
      irritation. In this study, a novel low-molecular-weight polysaccharide from
      Enteromorpha prolifera (LPE) was prepared by oxidation degradation, and LPE-iron
      (III) complex was synthesized and characterized. The molecular weight of LPE-iron
      (III) complex was 21.25kDa, and iron content was 25%. The therapeutic effects of
      LPE-iron (III) complex on IDA were investigated in rats. The hematological
      indices and organ coefficients of the rats were analyzed. Results showed a dose
      dependent relationship, and a prior intragastric administration of LPE-iron (III)
      complex (2mg Fe/kg body weight) exhibited considerable effect when compared with
      the positive control. Therefore, LPE-iron (III) complex could be exploited as a
      new iron fortifier.

PMID- 29223753
TI  - Preparation and characterization of biocomposite film based on chitosan and
      kombucha tea as active food packaging.
AB  - An active film composed of chitosan and kombucha tea (KT) was successfully
      prepared using the solvent casting technique. The effect of incorporation of KT
      at the levels 1%-3% w/w on the physical and functional properties of chitosan
      film was investigated. The antimicrobial activity of chitosan/KT film against
      Escherichia coli and Staphylococcus aureus was evaluated using agar diffusion
      test, and its antioxidant activity was determined using DPpH assay. The results
      revealed that incorporation of KT into chitosan films improved the water vapor
      permeability (from 256.7 to 132.1gcm-2h-1KPa-1mm) and enhanced the antioxidant
      activity of the latter up to 59% DPpH scavenging activity. Moreover, the
      incorporation of KT into the chitosan film increased the protective effect of the
      film against ultra violet (UV). Fourier transform infrared spectroscopic analysis
      revealed the chemical interactions between chitosan and the polyphenol groups of
      KT. In a minced beef model, chitosan/KT film effectively served as an active
      packaging and extended the shelf life of the minced beef as manifested in the
      retardation of lipid oxidation and microbial growth from 5.36 to 2.11logcfugr-1
      in 4days storage. The present work demonstrates that the chitosan/KT film not
      only maintains the quality of the minced beef but also, retards microbial growth
      significantly, extending the shelf life of the minced beef meat up to 3days;
      thus, chitosan/KT film is a potential material for active food packaging.

PMID- 29223754
TI  - The application of magnetically modified bacterial cellulose for immobilization
      of laccase.
AB  - The usefulness of bacterial cellulose (BC), obtained from the cultures of
      Komagataeibacter xylinus exposed to rotating magnetic field (RMF), as a carrier
      for laccase immobilization was investigated in this study. It was found that the
      highest yield of laccase immobilization (>70%) was achieved in pH of 4.0 and this
      value was optimal in the case of both types of cellulose carriers applied. The pH
      equals 4.0 was also the optimal one with regard to immobilized enzymes' activity,
      while in case of free laccase, optimal pH value was 3.0. Process of
      immobilization had an impact on enzyme's optimal temperatures: while free laccase
      and laccase bound to RMF-unexposed cellulose was the most effective at 60 degrees
      C, optimal activity of enzyme immobilized on RMF-exposed carrier was reached at
      70 degrees C. Laccase immobilized on both type of carriers had also better
      thermal stability at 70 degrees C compared to free laccase. After 8 cycles of
      use, laccase immobilized on RMF-exposed BC remained more active than laccase
      immobilized on RMF-unexposed BC (65% vs. 50% of initial activity, respectively).
      Our results indicate that RMF-modified BC may be successfully used as a carrier
      for the laccase immobilization.

PMID- 29223755
TI  - In situ biomineralization by silkworm feeding with ion precursors for the
      improved mechanical properties of silk fiber.
AB  - Possessing excellent biocompatibility, biodegradability and good reactive
      activity, silk fiber has been attracting great attention in biomedicine including
      surgical suture, drug delivery and tissue engineering. So far, several protocols
      have been developed to further improve the mechanical properties of the silk
      fiber. In current study, a novel in suit biomineralization strategy was developed
      to produce nano-hydroxyapatite (HA) strengthened silk fiber based on the natural
      alkaline condition in the body of silkworm by feeding the silkworm with ion
      precursors of Ca2+ and PO43- ions. Our observation proved that nanocomposite silk
      fiber contained more alpha-helix and random coil structures and fewer beta
      sheets. Tensile test showed that such obtained silk fiber has superior mechanical
      properties compared to normal silk fiber. To the best of our knowledge, no
      attempts have been made to fabricate the nanocomposite SF by in situ
      biomineralization and such protocol established in the current study may shed
      light on the investigation of nanoparticles reinforced silk fiber organisms of
      Bombyx mori.

PMID- 29223756
TI  - Microneedles: A versatile strategy for transdermal delivery of biological
      molecules.
AB  - Human skin is made up of multiple layers and is designed to protect the human
      body. The stratum corneum (SC), specifically, is a keratinized layer of skin
      through which molecules heavier than 500 Da cannot penetrate. Traditional methods
      of transdermal drug delivery through the SC, such as hypodermic needles, are less
      than ideal because their size and appearance can cause fear and pain, creating
      hesitation, limiting self-administration, and preventing their use in some
      patients altogether. A new technology has been developed to address these
      limitations, in which an array of needles, each microns in diameter and length,
      called microneedles, are able to pierce the skin's SC to deliver therapeutic
      agents without stimulating the proprioceptive pain nerves. These needles provide
      a strong advantage because they are capable of being incorporated into patches
      that can be conveniently self-administered by patients, while also offering the
      same bioabsorption and bioavailability currently provided by hypodermic needles.
      There have been many advancements in microneedle fabrication, and there are
      currently many variations of microneedle technology. Therefore, the purpose of
      this review is to provide a broad, introductory summary of current microneedle
      technology.

PMID- 29223757
TI  - Recent advances in carbon nanotube based electrochemical biosensors.
AB  - There is an increasing need for rapid, low cost, reusable, reliable and sensitive
      detection systems for diagnosing infectious diseases, metabolic disorders,
      rapidly advancing cancers and detecting the presence of environmental pollutants.
      Most traditional methods are invasive, slow, expensive and laborious, requiring
      highly specialized instruments. Introduction of biosensors with nanomaterials as
      transducers of signals have helped in removing the disadvantages associated with
      traditional detectors. The properties of high mechanical strength, better
      electrical conductivity and ability to serve as efficient signal transducers make
      carbon nanotubes (CNTs) ideal material for biosensor applications among the gamut
      of nanomaterials. Further, CNTs with their high surface areas, easily
      functionalizable surfaces for receptor immobilization are gaining importance in
      the construction of biosensors. The expanding field of CNTs bridges the physical
      sciences with biology, as chemical methods are employed to develop novel tools
      and platforms for understanding biological systems, in disease diagnosis and
      treatment. This review presents recent advances in surface functionalization of
      CNTs necessary for immobilization of enzymes and antibodies for biosensor
      applications and the methodologies used for the detection of a number of chemical
      and biological species. The review ends with a speculation on future prospects
      for CNTs in biology and medicine.

PMID- 29223758
TI  - Biosynthesis and structural characterization of polyhydroxyalkanoates produced by
      Pseudomonas aeruginosa ATCC 27853 from long odd-chain fatty acids.
AB  - Pseudomonas aeruginosa ATCC 27853 was cultured on media containing long odd-chain
      fatty acids. Heptadecanoic, nonadecanoic, and heneicosanoic acids sustained cell
      growth and resulted in polyhydroxyalkanoate (PHA) accumulation when culturing was
      conducted under nitrogen starvation conditions. No PHA was produced using a
      complete or magnesium-deprived medium. The isolated polyesters were characterized
      by gas chromatography and liquid chromatography-electrospray ionization mass
      spectrometry (ESI-MS) of methanolyzed samples, 1H and 13C NMR spectroscopy, gel
      permeation chromatography, ESI MS of partially pyrolyzed samples, and
      differential scanning calorimetry. These PHAs are composed of seven different odd
      chain repeating units starting from 3-hydroxyvalerate, with the highest species
      being the, to date, unreported constituent 3-hydroxyheptadecanoate, and minor
      amounts of 2 or 3 even-chain comonomers. The PHAs are soft, sticky, rubber-like
      materials having glass transition temperatures between -45 and -39 degrees C,
      melting temperatures between 48 and 52 degrees C, enthalpies of melting around
      11J/g, and molar masses ranging from 77 to 188kg/mol. Statistical analysis of the
      ESI mass spectra of the products of their partial pyrolysis showed that they are
      pure copolymers and not a blend of copolymers or homopolymers.

PMID- 29223759
TI  - Methotrexate loaded gellan gum microparticles for drug delivery.
AB  - Recently, polysaccharides based microparticles have been found to offer an
      attractive potential as a carrier in drug delivery field. In this study, bare
      gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum
      microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion
      solvent diffusion method. The developed microparticles (MPs) were found
      discretely distributed in a spherical shape. MTX has been encapsulated in
      microparticles with 84.8 +/- 1.68% encapsulation efficiency (%EE) and 6.45 +/-
      0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR)
      characterization of the MPs clearly indicated the physical encapsulation of MTX
      into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization
      showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG
      MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h.
      The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs)
      showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX
      GG MPs are biocompatible.

PMID- 29223760
TI  - Down the local: A qualitative case study of daytime drinking spaces in the London
      Borough of Islington.
AB  - BACKGROUND: Recognising the lack of research on daytime drinking practices in
      areas with managed night-time economies (NTEs), this qualitative study explores
      the phenomena in the London Borough of Islington; a rapidly gentrifying area with
      a highly regulated night-time economy (NTE). The objectives were to (i)
      Characterise the daytime drinking spaces of the local alcohol environment and
      (ii) Theorise the ways in which these spaces, and the practices and
      performativities within them, are situated within broader social and economic
      trends. METHODS: Adopting a legitimate peripheral participation approach to data
      collection, 39 licensed premises were visited in Islington and on-site
      observations carried out between the hours of 12 pm and 6 pm using a semi
      structured observation guide. Observations were written-up into detailed
      fieldnotes, uploaded to NVivo and subject to a thematic analysis. FINDINGS: The
      daytime on-premises alcohol environment was characterised by two main trends: the
      decline of traditional pubs and a proliferation of hybrid establishments in which
      alcohol was framed as part of a suite of attractions. The consumption trends that
      the latter exemplify are implicated in processes of micro-cultural production and
      'hipster capitalism'; and it is via this framing that we explore the way the
      diverse local drinking spaces were gendered and classed. Hybrid establishments
      have been regarded as positive in terms of public health, crime and safety.
      However, they could also help introduce drinking within times and contexts where
      it was not previously present. CONCLUSION: The intersection of an expanding
      hipster habitus with Local Authority efforts to tackle 'determined drunkenness'
      create very particular challenges. The operating practices of hybrid venues may
      feed into current alcohol industry strategies of promoting 'new moments' in which
      consumers can drink. They blur the divisions between work and play and produce
      temporal and classed divisions of drinking.

PMID- 29223761
TI  - Chemsex, risk behaviours and sexually transmitted infections among men who have
      sex with men in Dublin, Ireland.
AB  - BACKGROUND: Drug use for or during sex ('chemsex') among MSM has caused concern,
      because of the direct effects of the drugs themselves, and because of an
      increased risk of transmission of sexually transmitted infections (STIs). This
      study aimed to assess the prevalence of chemsex, associated behaviours and STIs
      among attendees at Ireland's only MSM-specific sexual health clinic in Dublin
      over a six week period in 2016. METHODS: The questionnaire collected demographic
      data, information on sexuality and sexual practice, self-reported history of
      treatment for STIs, and chemsex use. Key variables independently associated with
      treatment for STIs over the previous 12 months were identified using
      multivariable logistic regression. RESULTS: The response rate was 90% (510/568).
      One in four (27%) reported engaging in chemsex within the previous 12 months.
      Half had taken >=2 drugs on his last chemsex occasion. One in five (23%) reported
      that they/their partners had lost consciousness as a result of chemsex. Those
      engaging in chemsex were more likely to have had more sexual partners(p<0.001),
      more partners for anal intercourse (p<0.001) and to have had condomless anal
      intercourse(p=0.041). They were also more likely to report having been treated
      for gonorrhoea over the previous 12 months (adjusted OR 2.03, 95% CI 1.19-3.46,
      p=0.009). One in four (25%) reported that chemsex was impacting negatively on
      their lives and almost one third (31%) reported that they would like help or
      advice about chemsex. CONCLUSION: These results support international evidence of
      a chemsex culture among a subset of MSM. They will be used to develop an
      effective response which simultaneously addresses addiction and sexual ill-health
      among MSM who experience harm/seek help as a consequence of engagement in
      chemsex.

PMID- 29223762
TI  - Radioactivity levels in the atomic mineral occurrences along Dharmapuri Shear
      zone in parts of Vellore, Krishnagiri, Dharmapuri and Salem districts of Tamil
      Nadu, India.
AB  - The aim of this study was to evaluate the concentrations of naturally occurring
      radioactive nuclides 226Ra, 232Th and 40K and corresponding dose rates over
      atomic mineral occurrences of Dharmapuri shear zone in parts of Salem,
      Dharmapuri, Krishnagiri, and Vellore districts of Tamilnadu, India. In this
      paper, area-wise ternary diagrams of Ra, Th and K were plotted to study their
      relative concentration in the samples. Correlation study was also carried out to
      delineate the contribution of individual radionuclides toward the measured gamma
      dose rate. The concentrations of Ra, Th and K were determined by gamma ray
      spectrometry system using a 5" * 4" NaI (Tl) detector assembly. The geometric
      mean values of the estimated annual effective outdoor dose equivalent (AEDE) in
      mSv/y in the four areas were 2.35, 0.72, 1.88 and 0.36. A good linear correlation
      was observed between the estimated and measured annual effective dose equivalent.

PMID- 29223763
TI  - DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile
      seizures.
AB  - Mutations and copy number variants affecting DYRK1A gene encoding the dual
      specificity tyrosine phosphorylation-regulated kinase 1A are among the most
      frequent genetic causes of neurodevelopmental disorders including autism spectrum
      disorder (ASD) associated with microcephaly, febrile seizures and severe speech
      acquisition delay. Here we developed a mouse model harboring a frame-shift
      mutation in Dyrk1a resulting in a protein truncation and elimination of its
      kinase activity site. Dyrk1a+/- mice showed significant impairments in cognition
      and cognitive flexibility, communicative ultrasonic vocalizations, and social
      contacts. Susceptibility to hyperthermia-induced seizures was also significantly
      increased in these mice. The truncation leading to haploinsufficiency of DYRK1A
      in mice thus recapitulates the syndromic phenotypes observed in human patients
      and constitutes a useful model for further investigations of the mechanisms
      leading to ASD, speech delay and febrile seizures.

PMID- 29223764
TI  - Hypoxia-induced and HIF1alpha-VEGF-mediated tight junction dysfunction in
      choriocarcinoma cells: Implications for preeclampsia.
AB  - INTRODUCTION: Accumulated data indicate that placental hypoxia is implicated in
      the pathogenesis of preeclampsia (PE). Tight junction (TJ) is important structure
      that sustains normal placental barrier function, its dysregulation under hypoxia
      has been observed. This study was designed to explore hypoxia-induced TJ
      dysfunction in trophoblast cells and its possible involvement in PE
      pathophysiology. METHODS: Choriocarcinoma cells were grown in a monolayer and
      treated with cobalt chloride (CoCl2) to induce hypoxia. TJ architecture was
      assessed using transmission electron microscopy, and locations of TJ proteins
      were determined by immunofluorescence. TJ functions were assessed by
      transepithelial electrical resistance (TER) and increased cell paracellular
      permeability (CPP), and the expression of TJ-related proteins, HIF-1alpha and
      VEGF was measured. RESULTS: The TJ functions of trophoblast cells were
      significantly altered by hypoxia; TER decreased and CPP increased in a time- and
      concentration-dependent manner. Significant alterations in TJ protein expression
      and increases in HIF1alpha and VEGF expression were observed in hypoxic cells,
      and these effects were attenuated by pretreatment with YC-1. Moreover,
      corresponding changes in TJ protein expression were also detected in preeclamptic
      placentas. CONCLUSION: These data demonstrate that trophoblast cells undergo
      significant changes in TJ protein expression under hypoxic conditions and
      highlight the potential significance of the HIF1alpha-VEGF axis in the regulation
      of TJ structure and function in the preeclamptic placenta.

PMID- 29223765
TI  - Prognostic role of serum total cholesterol and high-density lipoprotein
      cholesterol in cancer survivors: A systematic review and meta-analysis.
AB  - BACKGROUND: The alterations of lipid profile in cancer has been reported to be
      associated with cancer development. However, the prognostic value of serum lipid
      markers level in cancer is currently under debate. Here we performed a meta
      analysis to investigate the prognostic significance of serum blood total
      cholesterol (TC), Triglycerides (TG), high-density lipoprotein cholesterol (HDL
      C) and low-density lipoprotein cholesterol (LDL-C) for cancer. METHODS: We
      systematically searched in PubMed and EMBASE for follow-up studies to evaluate
      the association between blood TC, TG, HDL-C, LDL-C and overall survival (OS) or
      disease-free survival (DFS) in patients with cancer. Pooled hazard ratio (HR) and
      95% CIs were pooled using the random models. Subgroup and sensitivity analyses
      were also performed. RESULTS: Twenty-six studies including 24655 individuals were
      identified. For patients with higher TC before diagnosis, the summary HR were
      0.82 (95% CI 0.75-0.90) for OS, 0.920 (95% CI, 0.849-0.997) for DFS. Patients
      with higher HDL-C had a 37% reduced risk of death compared with lower HDL-C (HR
      0.63, 95%CI 0.47-0.86, P<0.001). As for DFS, patients with higher HDL-C level had
      the risk of disease relapse reduced by 35% (HR 0.65, 95% CI, 0.48-0.89, P<0.001)
      compared with patients with lower levels. CONCLUSIONS: After pooled analysis,
      only TC and HDL-C were significantly associated with cancer survival. Our
      findings demonstrate for the first time that serum TC and HDL-C was identified as
      a protective factor for overall survival in cancer patients.

PMID- 29223766
TI  - Developing a value proposition for high-sensitivity troponin testing.
AB  - Laboratories are looking for ways that they can identify and deliver value
      through their service rather than just provide high quality test results. One way
      to demonstrate value has been described in the form of a value proposition where
      the application of a laboratory test is described explicitly in terms of the
      process of care and the patient outcomes. We have applied this concept to the use
      of high sensitivity troponin assays for the assessment of patients with suspected
      acute coronary syndrome. From a previously described framework we use a checklist
      to describe the various steps in the complete intervention or clinical pathway,
      demonstrating how the test should be used, highlighting key evidence in the
      literature that supports the intervention and list some of the measures which can
      be used to assess how well the intervention is being adopted and implemented.
      While the value proposition concept is based on the foundations of evidence based
      medicine it also requires collaboration between the laboratory and other
      stakeholders including clinicians to ensure that appropriate resources are
      applied across the complete clinical pathway in order to ensure its
      effectiveness.

PMID- 29223767
TI  - Evaluation of a National Pediatric Subinternship Curriculum Implemented Through
      Individual Learning Plans.
AB  - OBJECTIVE: The Council on Medical Student Education in Pediatrics and Association
      of Pediatric Program Directors developed a Pediatric Subinternship (CAPS)
      curriculum for use with an individualized learning plan (ILP). The authors
      determined which learning objectives (LOs) pediatric subinterns selected when
      provided the CAPS curriculum, summarized students' self-reported progress, and
      determined feasibility of ILPs in subinternship. METHODS: Students from 10
      medical schools completed a standardized ILP during pediatric subinternship.
      Students listed >=3 LOs using CAPS curriculum as a guide and self-assessed their
      progress. Students reviewed ILPs with faculty preceptors; preceptors completed
      questionnaires on time and effort spent. Authors mapped student LOs to CAPS
      curriculum objectives and grouped in Accreditation Council for Graduate Medical
      Education competency domains. RESULTS: Two hundred four students documented 850
      LOs. Authors mapped student LOs to 61 of the 69 CAPS objectives (88%). Students
      most commonly chose Patient Care LOs, with the top 3 related to oral
      presentations, time management, and management plans. Student LOs not in CAPS
      addressed nutrition, child development, test interpretation, and cost. No
      students chose LOs related to health disparities, shared decision making,
      informed consent, or patient safety. Students self-reported significant progress
      on most LOs (73%). Faculty met with students >=1 time and 93% met for a total of
      <=1 hour. According to faculty, students required little or no help completing
      ILPs. CONCLUSIONS: Students chose a wide range of LOs when provided the CAPS
      curriculum. Revision to include additional student-identified LOs would enhance
      CAPS curriculum's comprehensiveness. Using this curriculum with an ILP during
      subinternship is feasible, but gaps between educator-identified and student
      identified objectives require further exploration.

PMID- 29223769
TI  - Obstructive sleep apnoea and Alzheimer's disease: In search of shared
      pathomechanisms.
AB  - Alzheimer's disease (AD) is a significant public health concern. The incidence
      continues to rise, and it is set to be over one million in the UK by 2025. The
      processes involved in the pathogenesis of AD have been shown to overlap with
      those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA).
      Currently, the standard treatment for OSA is Continuous Positive Airway Pressure.
      Adherence to treatment can, however, be an issue, especially in patients with
      dementia. Also, not all patients respond adequately, necessitating the use of
      additional treatments. Based on the body of data, we here suggest that excessive
      and prolonged neuronal activity might contribute to genesis and acceleration of
      both AD and OSA in the absence of appropriately structured sleep. Further, we
      argue that external factors, including systemic inflammation and obesity, are
      likely to interfere with immunological processes of the brain, and further
      promote disease progression. If this hypothesis is proven in future studies, it
      could have far-reaching clinical translational implications, as well as
      implications for future treatment strategies in OSA.

PMID- 29223768
TI  - Verbal learning and hippocampal dysfunction in schizophrenia: A meta-analysis.
AB  - This meta-analysis summarizes research examining whether deficits in verbal
      learning are related to bilateral hippocampal volume reductions in patients with
      or at risk for schizophrenia and in healthy controls. 17 studies with 755
      patients with schizophrenia (SCZ), 232 Genetic High Risk (GHR) subjects and 914
      healthy controls (HC) were included. Pooled correlation coefficients were
      calculated between hemisphere (left, right or total) and type of recall
      (immediate or delayed) for each diagnostic group individually (SCZ, GHR and HC).
      In SCZ, left and right hippocampal volume positively correlated with immediate
      (r=0.256, 0.230) and delayed (r=0.132, 0.231) verbal recall. There was also a
      correlation between total hippocampal volume and delayed recall (r=0.233). None
      of these correlations were significant in healthy controls. There was however, a
      positive correlation between left hippocampal volume and immediate recall in the
      GHR group (r=0.356). The results suggest that hippocampal volume affects
      immediate and delayed verbal learning capacity in schizophrenia and provides
      further evidence of hippocampal dysfunction in the pathophysiology of
      schizophrenia.

PMID- 29223770
TI  - Rhythmic facilitation of sensory processing: A critical review.
AB  - Here we review the role of brain oscillations in sensory processing. We examine
      the idea that neural entrainment of intrinsic oscillations underlies the
      processing of rhythmic stimuli in the context of simple isochronous rhythms as
      well as in music and speech. This has been a topic of growing interest over
      recent years; however, many issues remain highly controversial: how do
      fluctuations of intrinsic neural oscillations-both spontaneous and entrained to
      external stimuli-affect perception, and does this occur automatically or can it
      be actively controlled by top-down factors? Some of the controversy in the
      literature stems from confounding use of terminology. Moreover, it is not
      straightforward how theories and findings regarding isochronous rhythms
      generalize to more complex, naturalistic stimuli, such as speech and music. Here
      we aim to clarify terminology, and distinguish between different phenomena that
      are often lumped together as reflecting "neural entrainment" but may actually
      vary in their mechanistic underpinnings. Furthermore, we discuss specific caveats
      and confounds related to making inferences about oscillatory mechanisms from
      human electrophysiological data.

PMID- 29223773
TI  - A Promise to Our Patients to Mind Neurodevelopment.

PMID- 29223772
TI  - Problem Delayed Does Not Mean Solution Denied.

PMID- 29223774
TI  - Physiological and proteomic responses to corticosteroid treatments in Eurasian
      perch, Perca fluviatilis: Investigation of immune-related parameters.
AB  - The comparative effects of cortisol and 11-deoxycorticosterone (DOC), two major
      corticosteroids in fish, have yet received little attention in teleosts. We
      evaluated the proteomic and immune responses of Eurasian perch to chronic
      corticosteroid treatments. We implanted immature perch with cortisol (80mg/kg) or
      DOC (4mg/kg) and measured the proportions of blood leucocytes, immune indices in
      the plasma, spleen and liver (complement and lysozyme activity, total
      immunoglobulin and immune gene expression in the tissues) and differential
      proteome expression (corticosteroid versus control) in the liver and the spleen
      on days 2, 4 and 14 post-treatment. Implantation of cortisol decreased the ratio
      of blood leucocytes and depressed Ig levels in both organs while DOC modulated
      the proportion of leucocyte sub-populations (increase in lymphocytes and decrease
      in granulocytes). In contrast, the innate humoral immunity was not strongly
      influenced by any of corticosteroid implants. The only immune parameter that was
      significantly affected was lysozyme, after DOC treatment. A number of proteins
      were differentially regulated by these hormones and some were identified in the
      liver (21 for cortisol and 8 for DOC) and in the spleen (10 for cortisol and 10
      for DOC). None of the proteins was directly linked to immunity, except the
      natural killer enhancing factor, which was repressed by cortisol in the spleen.
      Our results also confirm that the proteins involved in energetic and glucose
      metabolism are affected by corticosteroids. Furthermore, these corticosteroids
      differently regulate immune status in Eurasian perch and they primarily impact
      leucocytes, as opposed to innate immune function.

PMID- 29223771
TI  - Comparative studies of social buffering: A consideration of approaches,
      terminology, and pitfalls.
AB  - KIYOKAWA, Y. and HENNESSY, M.B. Comparative studies of social buffering: A
      consideration of approaches, terminology, and pitfalls...NEUROSCI BIOBEHAV REV
      XXX-XXX, .- Over the past decades, there has been an increasing number of
      investigations of the impact of social variables on neural, endocrine, and immune
      outcomes. Among these are studies of "social buffering"-or the phenomenon by
      which affiliative social partners mitigate the response to stressors. Yet, as
      social buffering studies have become more commonplace, the variety of approaches
      taken, definitions employed, and divergent results obtained in different species
      can lead to confusion and miscommunication. The aim of the present paper,
      therefore, is to address terminology and approaches and to highlight potential
      pitfalls to the study of social buffering across nonhuman species. We review and
      categorize variables currently being employed in social buffering studies and
      provide an overview of responses measured, mediating sensory modalities and
      underlying mechanisms. It is our hope that the paper will be useful to those
      contemplating examination of social buffering in the context of their own
      research.

PMID- 29223775
TI  - Association between prenatal bisphenol A and phthalate exposures and fetal
      metabolic related biomarkers: The Hokkaido study on Environment and Children's
      Health.
AB  - Bisphenol A and phthalates are widely detected in human urine, blood, breast
      milk, and amniotic fluid. Both bisphenol A and phthalates have been suggested as
      playing a role in obesity epidemics. Exposure to these chemicals during fetal
      development, and its consequences should be concerning because they can cross the
      placenta. Thus, this study aimed to assess the association between prenatal
      exposure to bisphenol A and phthalates, and cord blood metabolic-related
      biomarkers. Maternal serum was used during the first trimester, to determine
      prenatal exposure to bisphenol A and phthalates. Levels of metabolic-related
      biomarkers in the cord blood were also determined. Linear regression models were
      applied to the 365 participants with both, exposure and biomarker assessments,
      adjusted for maternal age, pre-pregnancy body mass index, parity, education, and
      sex of the child. The level of bisphenol A was negatively associated with the
      leptin level (beta = -0.06, 95% confidence interval [CI]: -0.11, -0.01), but was
      positively associated with the high-molecular-weight adiponectin level, with
      marginal significance (beta = 0.03, 95%CI: 0.00, 0.06). The mono-isobutyl
      phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate
      (MEHP), and summation of MEHP and MECPP to represent DEHP exposure (?DEHPm)
      levels were inversely associated with the leptin levels (beta=-0.14, 95%CI: 
      0.27, -0.01; beta = -0.12, 95%CI: -0.24, 0.00 with marginal significance;
      beta=0.08, 95%CI: -0.14, -0.03; and beta = -0.09, 95%CI: -0.16, -0.03,
      respectively). The present study provided some evidence that prenatal exposure to
      bisphenol A and certain phthalates may modify fetal adiponectin and leptin
      levels.

PMID- 29223776
TI  - Impact of edaphic factors and nutrient management on the hepatoprotective
      efficiency of Carlinoside purified from pigeon pea leaves: An evaluation of
      UGT1A1 activity in hepatitis induced organelles.
AB  - Carlinoside is a unique compound well-known for its excellent curative potential
      in hepatitis. There is a substantial research gap regarding the medicinal use of
      carlinoside, as its concentrations are greatly variable (depending on locality).
      We cultivated Cajanus cajan using vermicompost as a major organic amendment at
      two locations (Sonitpur and Birbhum) with different soil types, but identical
      climate conditions. Sonitpur soils were richer in soil organic C (SOC), enzyme
      activation, and N/P content than Birbhum. However, vermi-treatment improved many
      soil properties (bulk density, water retention, pH, N/P/K, and enzyme activity)
      to narrow the locational gap in soil quality by 15-28%. We also recorded a many
      fold increment in SOC storage capacities in both locations, which was
      significantly correlated with carlinoside, total phenol, and flavonoid contents
      in Cajanus leaves. This significantly up-regulated the carlinoside induced
      expression of the bilirubin-solubilizing UGT1A1enzyme in HepG2 cell and rat
      liver. Leaf extracts of vermicompost-aided plants could cure hepatitis in
      affected rat livers and in the HepG2 cell line. Accordingly, vermi-treatment is
      an effective route for the growth of Cajanus as a cash crop for biomedical
      applications and can produce a concurrent improvement in soil quality.

PMID- 29223778
TI  - Differences in trochlear parameters between native and prosthetic kinematically
      or mechanically aligned knees.
AB  - INTRODUCTION: Kinematic (KA) and mechanical (MA) alignment techniques are two
      different philosophies of implant positioning that use the same TKA implants.
      This might generate differences in the resulting prosthetic trochleae parameters
      between the two techniques of alignment. Our study aim was to test the following
      hypotheses : (1) mechanically or kinematically aligned femoral implant
      understuffs the native trochlear articular surface and poorly restores the native
      groove orientation, and (2) the orientation of the prosthetic trochlear groove
      and trochlear fill are different between MA and KA. METHODS: Three-dimensional
      models of the femur were made from segmentation of preoperative Magnetic
      Resonance Imaging scans (MRIs) of ten subjects with isolated medial tibiofemoral
      osteoarthritis. In-house planning and analysis software kinematically and
      mechanically aligned a modern cruciate retaining femoral component and determined
      differences in parameters of the trochlear fit between native and prosthetic
      trochleae, and between KA and MA prosthetic trochleae. RESULTS: The MA prosthetic
      trochleae did not fill (understuffed) the entire length of the native medial
      facet and the proximal 70% of the native groove and lateral facet, and oriented
      the trochleae groove 8 degrees  more valgus than native. The KA prosthetic
      trochleae understuffed the proximal 70% of the native trochleae, and had a groove
      6 degrees  more valgus than native. The KA trochleae understuffed the medial
      facet distally and oriented the groove 2 degrees  less valgus and 3 degrees  more
      internally rotated than the MA trochleae. CONCLUSION: MA and KA prosthetic
      trochleae substantially understuff and create a prosthetic groove more valgus
      compared to native trochlear anatomy, and they also differed between each other
      regarding trochleae stuffing and groove alignment. Although randomized trials
      have not shown differences in patellofemoral complications between KA and MA, a
      femoral component designed specifically for KA that more closely restores the
      native trochlear anatomy might improve patient reported satisfaction and
      function. LEVEL OF EVIDENCE: Level 2 controlled laboratory study.

PMID- 29223777
TI  - Child care centre adherence to infant physical activity and screen time
      recommendations in Australia, Canada and the United States: An observational
      study.
AB  - OBJECTIVE: The aim of this study was to compare adherence to physical activity
      and sedentary behaviour recommendations within the 2011 Institute of Medicine
      Early Childhood Obesity Prevention Policies as well as screen time
      recommendations from the 2013 American Academy of Pediatrics for samples of
      infants in child care centres in Australia, Canada, and the United States (US).
      METHODS: This cross-sectional study used data from: the Australian 2013 Standing
      Preschools (N=9) and the 2014-2017 Early Start Baseline (N=22) studies; the 2011
      Canadian Healthy Living Habits in Pre-School Children study (N=14); and the
      American 2008 (N=31) and 2013-2017 (N=31) Baby Nutrition and Physical Activity
      Self-Assessment for Child Care (NAP SACC) trials. Data were compared on the above
      infant recommendations. Percentages were used to describe compliance to the
      recommendations and chi-square tests to determine whether compliance differed by
      country. RESULTS: Child care centres were most compliant (74%-95%) with
      recommendations to: provide daily indoor opportunities for infants to move freely
      under adult supervision, daily tummy time for infants less than 6 months of age,
      indoor and outdoor recreation areas that encourage infants to be physically
      active, and discourage screen time. Centres were least compliant (38%-41%) with
      adhering to recommendations to: limit the use of equipment that restricts an
      infant's movement and provide education about physical activity to families.
      Compared with Canadian and US centres, Australian centres were less compliant
      (46%) with the recommendation to engage with infants on the ground each day, to
      optimize adult-infant interactions and to limit the use of equipment that
      restricts the infant's movement. Canadian centres were less compliant (39%) with
      the recommendation to provide training to staff and education to parents about
      children's physical activity. US centres were less compliant (25%-41%) with the
      recommendations to provide daily opportunities for infants to explore their
      outdoor environment, limit the use of equipment that restricts the infant's
      movement and provide education to families about children's physical activity.
      CONCLUSIONS: Assisting child care centres on limiting the use of equipment that
      restricts an infant's movement, and providing education about children's physical
      activity to families may be important targets for future interventions.

PMID- 29223779
TI  - Female verbal memory advantage in temporal, but not frontal lobe epilepsy.
AB  - Women show better performance than men on a range of episodic memory tasks.
      Evidence regarding a neuroanatomical localization of this effect remains
      ambiguous. It has been suggested that anterior temporal lobe structures are
      responsible for sex differences in verbal memory, yet temporal lobe epilepsy
      (TLE) and TLE surgery do not affect women's verbal memory advantage. Instead,
      frontal lobe regions may be relevant for female verbal memory superiority, i.e.
      by enabling more efficient encoding and retrieval strategies in women. The aim of
      the present study was to investigate whether women's verbal memory advantage can
      be found in patients with frontal lobe epilepsy (FLE), and how patients with FLE
      and those with TLE differ with regard to sex differences in verbal memory. Fifty
      patients with unilateral FLE (26 women, 24 men) were compared with 183 patients
      with unilateral TLE (90 women, 93 men) on both verbal learning and delayed
      memory. We found that women showed better verbal memory than men in the TLE
      group, but not in the FLE group. In addition, we found that patients with TLE
      showed worse verbal learning than those with FLE. Our findings support the idea
      that women's advantage in verbal memory may be related to frontal lobe function.

PMID- 29223780
TI  - Drug-resistant epilepsy in MELAS: safety and potential efficacy of lacosamide.

PMID- 29223781
TI  - Enhanced sludge solubilization and dewaterability by synergistic effects of
      nitrite and freezing.
AB  - In this study, nitrite was added into sludge during freezing process to evaluate
      its role in waste activated sludge (WAS) solubilization and effect on sludge
      dewatering characteristics. The results showed that the introduction of 100 mg L
      1 of nitrite could increase dissolved organic carbon (DOC) concentration from
      29.5 to 48.8 mg DOC g-1 VSS under freezing conditions. More DOC was released with
      the increase of nitrite concentration. Freezing temperature, or freezing speed,
      also played a role in sludge solubilization. It was found that some readily
      biodegradable low molecular weight (LMW) compounds, e.g. LMW protein, LMW
      polysaccharide, LMW neutrals, building blocks and LMW acids, were mainly released
      during the freezing process with the presence of nitrite. Interestingly, nitrite
      could also improve the sludge filterability at the lower nitrite concentration as
      a result of the increased sludge particle size. However, electrolytes (sodium
      nitrite) addition effects may mask such enhancement when nitrite concentration
      was high (800 mg L-1). The rheological characteristics of sludge could be well
      modeled by Herchel-Bulkley model and the introduction of nitrite into freezing
      process further increased sludge flowability and decreased sludge viscosity.
      These results indicated that freezing with the presence of suitable concentration
      of nitrite could promote sludge solubilization and dewaterability. As such, good
      liquid and solid separation can be achieved with the recovery of liquid stream as
      carbon source.

PMID- 29223782
TI  - The influence of precursors and treatment process on the formation of Iodo-THMs
      in Canadian drinking water.
AB  - The National Survey of Disinfection By-Products and Selected Emerging
      Contaminants investigated the formation of various disinfection by-products and
      contaminants in 65 water treatment systems (WTSs) across Canada. Results for six
      iodo-trihalomethanes (iodo-THMs) are reported in this paper. The participating
      water treatment systems included large, medium and small systems using water
      sources and treatment processes which were representative of Canadian drinking
      water. Five water samples (source water, treated water and three water samples
      along the distribution system) were collected from each treatment system, both
      under winter and summer conditions. Samples were stabilized, shipped cold and
      analysed for six iodo-THMs (dichloroiodomethane-DCIM; dibromoiodomethane-DBIM;
      bromochloroiodomethane-BCIM; chlorodiiodomethane-CDIM; bromodiiodomethane-BDIM
      and triiodomethane or iodoform-TIM), using a SPME-GC-ECD method developed in our
      laboratory (MDLs from 0.02 MUg/L for iodoform to 0.06 MUg/L for
      bromodiiodomethane). Concentrations of relevant precursors like dissolved organic
      carbon (DOC), bromide, iodide and total iodine, as well as other water quality
      parameters, were also determined. Detailed information about the treatment
      process used at each location was recorded using a questionnaire. The survey
      showed that one or more iodo-THMs were detected at 31 out of 64 water treatment
      systems (WTSs) under winter conditions and in 46 out of 64 WTSs under summer
      conditions (analytical results from one site were excluded due to sampling
      challenges). Total iodo-THM concentrations measured during this survey ranged
      from 0.02 MUg/L to 21.66 MUg/L. The highest total iodo-THM concentration was
      measured in WTS 63 where all six iodo-THMs were detected and iodoform was present
      in the highest concentration. The highest iodo-THM formation was found to occur
      in treatment systems where water sources had naturally occurring ammonium as well
      as high bromide, high iodide and/or total iodine concentrations. In two such
      water systems the total concentration of iodo-THMs exceeded the concentration of
      regulated THMs.

PMID- 29223783
TI  - Prior stress promotes the generalization of contextual fear memories: Involvement
      of the gabaergic signaling within the basolateral amygdala complex.
AB  - Fear generalization occurs when a response, previously acquired with a
      threatening stimulus, is transferred to a similar one. However, it could be
      maladaptive when stimuli that do not represent a real threat are appraised as
      dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a
      major risk factor for the occurrence of anxiety disorders and it is well
      established that it influences different phases of fear memory; nevertheless, its
      impact on the generalization of contextual fear memories has been less studied.
      In the present work, we have characterized the impact of acute restraint stress
      prior to contextual fear conditioning on the generalization of this fear memory,
      and the role of the GABAergic signaling within the basolateral amygdala complex
      (BLA) on the stress modulatory effects. We have found that a single stress
      exposure promoted the generalization of this memory trace to a different context
      that was well discriminated in unstressed conditioned animals. Moreover, this
      effect was dependent on the formation of a contextual associative memory and on
      the testing order (i.e., conditioning context first vs generalization context
      first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA
      midazolam administration prior to the stressful session exposure prevented the
      generalization of fear memory, whereas intra-BLA administration of the GABA-A
      antagonist (Bicuculline), prior to fear conditioning, induced the generalization
      of fear memory in unstressed rats. We concluded that stress exposure, prior to
      contextual fear conditioning, promotes the generalization of fear memory and that
      the GABAergic transmission within the BLA has a critical role in this phenomenon.

PMID- 29223784
TI  - Thalidomide attenuates development of morphine dependence in mice by inhibiting
      PI3K/Akt and nitric oxide signaling pathways.
AB  - Morphine dependence and the subsequent withdrawal syndrome restrict its clinical
      use in management of chronic pain. The precise mechanism for the development of
      dependence is still elusive. Thalidomide is a glutamic acid derivative, recently
      has been reconsidered for its clinical use due to elucidation of different
      clinical effects. Phosphoinositide 3-kinase (PI3K) is an intracellular transducer
      enzyme which activates Akt which in turns increases the level of nitric oxide. It
      is well established that elevated levels of nitric oxide has a pivotal role in
      the development of morphine dependence. In the present study, we aimed to explore
      the effect of thalidomide on the development of morphine dependence targeting
      PI3K/Akt (PKB) and nitric oxide (NO) pathways. Male NMRI mice and human
      glioblastoma T98G cell line were used to study the effect of thalidomide on
      morphine dependence. In both models the consequent effect of thalidomide on
      PI3K/Akt and/or NO signaling in morphine dependence was determined. Thalidomide
      alone or in combination with PI3K inhibitor, Akt inhibitor or nitric oxide
      synthase (NOS) inhibitors significantly reduced naloxone induced withdrawal signs
      in morphine dependent mice. Also, the levels of nitrite in hippocampus of
      morphine dependent mice were significantly reduced by thalidomide in compared to
      vehicle treated morphine dependent mice. In T98G human glioblastoma cells,
      thalidomide alone or in combination with PI3K and Akt inhibitors significantly
      reduced iNOS expression in comparison to the morphine treated cells. Also,
      morphine-induced p-Akt was suppressed when T98G cells were pretreated with
      thalidomide. Our results suggest that morphine induces Akt, which has a crucial
      role in the induction of NOS activity, leading to morphine dependence. Moreover,
      these data indicate that thalidomide attenuates the development of morphine
      dependence in vivo and in vitro by inhibition of PI3K/Akt and nitric oxide
      signaling pathways.

PMID- 29223785
TI  - Cortical thickness of planum temporale and pars opercularis in native language
      tone processing.
AB  - The present study investigated the relationship between linguistic tone
      processing and cortical thickness of bilateral planum temporale (PT) and pars
      opercularis of the inferior frontal gyrus (IFGpo). Swedish tones on word stems
      function as cues to upcoming endings. Correlating structural brain imaging data
      with participants' response time patterns for suffixes, we found that thicker
      cortex in the left PT was associated with greater reliance on tones to anticipate
      upcoming inflections on real words. On inflected pseudoword stems, however, the
      cortical thickness of left IFGpo was associated with tone-suffix processing. Thus
      cortical thickness of the left PT might play a role in processing tones as part
      of stored representations for familiar speech segments, most likely when
      inflected forms are accessed as whole words. In the absence of stored
      representations, listeners might need to rely on morphosyntactic rules specifying
      tone-suffix associations, potentially facilitated by greater cortical thickness
      of left IFGpo.

PMID- 29223786
TI  - The eukaryotic translation initiation factor 3 subunit E binds to classical swine
      fever virus NS5A and facilitates viral replication.
AB  - Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein,
      playing critical roles in viral RNA replication, translation and assembly. To
      further explore its functions in viral replication, interaction of NS5A with host
      factors was assayed using a his-tag "pull down" assay coupled with shotgun LC
      MS/MS. Host protein translation initiation factor 3 subunit E was identified as a
      binding partner of NS5A, and confirmed by co-immunoprecipitation and co
      localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic
      replication, viral protein expression and production of progeny virus, and
      downregulation of eIF3E by siRNA significantly decreased viral proliferation in
      PK-15 cells. Luciferase reporter assay showed an enhancement of translational
      activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in
      cellular translation by NS5A. These data indicate that eIF3E plays an important
      role in CSFV replication, thereby identifying it as a potential target for
      inhibition of the virus.

PMID- 29223787
TI  - A novel peptide-based vaccine candidate with protective efficacy against
      influenza A in a mouse model.
AB  - Current influenza vaccines mainly induce antibody responses to the variable
      hemagglutinin proteins of the virus strains included in the vaccine. Instead, a
      broadly protective influenza vaccine should aim at inducing antibody- and/or cell
      mediated immunity against conserved viral proteins. Vacc-FLU is a peptide based
      vaccine combining conserved B and T cell epitopes. Peptide selection was done
      using a proprietary peptide design platform technology focusing on responses to
      human leukocyte antigen (HLA)-restricted epitopes. Immunization of wild-type mice
      and mice transgenic for HLA-A2.1 with the peptide mix successfully induced both
      humoral and cell mediated immune responses. Partial protection from severe weight
      loss upon challenge was observed in both mouse strains but was stronger and
      observed at lower vaccine doses in transgenic mice. Our results show that the
      Vacc-FLU peptide mix is capable of inducing IFNgamma-producing T cells and
      antibody-producing B cells which can protect from severe disease symptoms upon
      infection.

PMID- 29223788
TI  - A multiplex real-time RT-PCR for simultaneous detection of four most common avian
      respiratory viruses.
AB  - A one-step multiplex real-time reverse transcription-PCR (rRT-PCR) assay was
      developed for simultaneous detection and quantification of four avian respiratory
      viruses: avian influenza virus (AIV), infectious bronchitis virus (IBV),
      Newcastle disease virus (NDV) and infectious laryngotracheitis virus (ILTV). In
      comparison with the singleplex rRT-PCR, the specificity, the sensitivity and the
      reproducibility of the new assay were evaluated and validated using 70 clinical
      samples. The optimal cutoff point, the corresponding limit of quantification
      (LoQ) and the limit of detection (LoD) were statistical established based on
      receiver operating characteristic (ROC) curve analysis. The results showed that
      the multiplex assay presents higher sensitivity and specificity. Correlation
      coefficients (R2) and amplification efficiencies (E) of all singleplex and
      multiplex rRT-PCR reactions are within the acceptable range. The 95% LoDs of
      multiplex assay were in the range [3-19] copies genomic/ ul, and its
      corresponding cutoff cycles were in the range [34.16-36.59]. No competitive
      inhibition for the detection of the four targets and no specific amplification or
      cross reactivity with other tested viruses was observed. Excellent results were
      attained in the inter-assay and intra-assay reproducibility evaluation. All
      identified samples by the multiplex rRT-PCR assay proved to be 100% concordant
      with the results of the singleplex assays. The results achieved showed that the
      multiplex assay is very suitable as a routine laboratory test for rapid and
      specific detection and quantification of co-infections in field samples.

PMID- 29223789
TI  - Medical and developmental outcomes of bevacizumab versus laser for retinopathy of
      prematurity.
AB  - BACKGROUND: Infants with stage 3+ retinopathy of prematurity (ROP) in zone I or
      zone II posterior were randomized to initial treatment with bevacizumab or laser
      in a multicenter trial (BEAT-ROP). The purpose of this study was to assess the
      effects of bevacizumab on nonophthalmologic outcomes. METHODS: At one study site,
      inborn infants of <27 weeks' gestational age underwent medical and standardized
      neurologic and developmental assessments at 18-22 months' corrected age (age
      after expected date of full-term delivery). RESULTS: Of the 18 infants enrolled
      at our site, 16 (7 bevacizumab, 9 laser) were evaluated for medical and
      neurodevelopmental outcomes at 18-28 months' corrected age. For each of the
      groups, the medians and ranges of growth percentiles were low compared with norms
      for healthy infants. The ranges for Bayley III developmental scores were also low
      relative to expected norms for healthy infants. There were no significant
      differences between the bevacizumab and laser therapy groups in weight (median
      percentile: bevacizumab, 18; laser, 7), length, head circumference, cerebral
      palsy, or Bayley scores (median Cognitive Composite Score: bevacizumab, 85;
      laser, 65). There was a significant difference in length of hospital stay (median
      days, 98 vs 140 days) favoring the bevacizumab group. CONCLUSIONS: In this
      patient cohort 2-year follow-up evaluation of infants treated with bevacizumab
      versus laser therapy for retinopathy of prematurity showed no adverse effects on
      medical or neurodevelopmental outcomes.

PMID- 29223790
TI  - Temporal and bi-directional associations between sleep duration and physical
      activity/sedentary time in children: An international comparison.
AB  - The purpose of this multinational and cross-sectional study was to investigate
      whether nighttime sleep duration was associated with physical activity (PA) and
      sedentary time (SED) the following day, whether daytime PA/SED were associated
      with sleep duration the subsequent night, and whether the associations were
      modified by sex and study sites. Data from 5779 children aged 9-11years were
      analyzed. A waist-worn Actigraph GT3X+ accelerometer was used to assess
      children's 24-h movement behaviours for 7days, i.e. sleep duration, total SED,
      light-intensity physical activity (LPA), and moderate- to vigorous-intensity
      physical activity (MVPA). Multilevel linear regression models were used to
      account for the repeated measures nested within participants (there were up to 7
      sleep->PA/SED and PA/SED->sleep pairings per participant) and schools, and
      adjusted for covariates. To facilitate interpretation, all sleep and PA/SED
      variables were standardized. Results showed that the relationship between sleep
      and PA/SED is bi-directional in this international sample of children.
      Specifically, for each one standard deviation (SD) unit increase in sleep
      duration, SED the following day decreased by 0.04 SD units, while LPA and MVPA
      increased by 0.04 and 0.02 SD units, respectively. Sleep duration decreased by
      0.02 SD units and increased by 0.04 SD units for each one SD unit increase in SED
      and MVPA, respectively. Sleep duration was not affected by changes in LPA. These
      associations differed across sex and study sites in both directions. However,
      since the observed effect sizes are subtle, public health initiatives should
      consider the clinical and practical relevance of these findings.

PMID- 29223791
TI  - Towards more effective online information support for mammography screening
      decisions.
AB  - We sought to determine the extent to which web-based patient-directed resources
      of U.S. public health agencies and professional groups offer consistent and
      relevant information on the benefits and harms of mammography screening. Between
      August 2016-February 2017, we identified, collected and analyzed information
      about mammography screening from the websites of 14 well-known governmental
      public health agencies and professional groups. We recorded and compared the
      qualitative and quantitative information the sites offered on (1) breast cancer
      mortality; (2) false-positive results; (3) unnecessary biopsy; and (4)
      overdetection. Our results show considerable variation on which benefits and
      harms are mentioned, whether they are discussed in qualitative and/or
      quantitative terms, and how this information is delivered and framed. We argue
      that it is ethically problematic that benefit and harm information is presented
      in inconsistent and incomplete ways, and we suggest that organizations work
      towards the adoption of uniform categories to genuinely support preference
      sensitive decision making.

PMID- 29223792
TI  - Prediction of persistent hemodynamic depression after carotid angioplasty and
      stenting using artificial neural network model.
AB  - OBJECTIVES: To assess and compare predictive factors for persistent hemodynamic
      depression (PHD) after carotid artery angioplasty and stenting (CAS) using
      artificial neural network (ANN) and multiple logistic regression (MLR) or support
      vector machines (SVM) models. PATIENTS AND METHODS: A retrospective data set of
      patients (n=76) who underwent CAS from 2007 to 2014 was used as input (training
      cohort) to a back-propagation ANN using TensorFlow platform. PHD was defined when
      systolic blood pressure was less than 90mmHg or heart rate was less 50 beats/min
      that lasted for more than one hour. The resulting ANN was prospectively tested in
      33 patients (test cohort) and compared with MLR or SVM models according to
      accuracy and receiver operating characteristics (ROC) curve analysis. RESULTS: No
      significant difference in baseline characteristics between the training cohort
      and the test cohort was observed. PHD was observed in 21 (27.6%) patients in the
      training cohort and 10 (30.3%) patients in the test cohort. In the training
      cohort, the accuracy of ANN for the prediction of PHD was 98.7% and the area
      under the ROC curve (AUROC) was 0.961. In the test cohort, the number of
      correctly classified instances was 32 (97.0%) using the ANN model. In contrast,
      the accuracy rate of MLR or SVM model was both 75.8%. ANN (AUROC: 0.950; 95% CI
      [confidence interval]: 0.813-0.996) showed superior predictive performance
      compared to MLR model (AUROC: 0.796; 95% CI: 0.620-0.915, p<0.001) or SVM model
      (AUROC: 0.885; 95% CI: 0.725-0.969, p<0.001). CONCLUSIONS: The ANN model seems to
      have more powerful prediction capabilities than MLR or SVM model for persistent
      hemodynamic depression after CAS. External validation with a large cohort is
      needed to confirm our results.

PMID- 29223793
TI  - Overexpression of G-protein-coupled receptors 65 in glioblastoma predicts poor
      patient prognosis.
AB  - OBJECTIVE: G-protein-coupled receptors 65 (GPR65), identified as an acid-sensing
      receptor, is overexpressed in several malignancies and promote tumor development.
      Our aim was to investigate the expression and prognostic value of GPR65 in
      glioblastoma. MATERIALS AND METHODS: We determined the expression of GPR65
      protein using immunohistochemistry in tissue microarrays containing 11 Grade I,
      107 Grade II, 47 Grade III, and 102 Grade IV gliomas and 16 normal brains. Then
      we evaluated its association with pathological grades, prognosis, and recurrence.
      The Cancer Genome Atlas (TCGA) group (N=528) was further employed to examine
      transcriptional level of GPR65 in glioblastoma and the correlation between GPR65
      expression and clinical outcome. RESULTS: In our cohort, GPR65 expression was
      positively related to glioma pathological grade (p<0.01) and elevated in
      glioblastoma (p<0.01). High expression of GPR65 was associated with significantly
      short overall survival (OS) (p=0.013) and progression-free survival (PFS)
      (p=0.029), and could be identified as an independent risk factor for OS of
      glioblastoma patients (Hazard Ratio [HR]=1.596, p=0.037). As an aiding evidence,
      increased GPR65 mRNA expression was also found in TCGA glioblastoma group
      (p<0.001) and its high level predicted a poor clinical outcome (OS, p=0.003; PFS,
      p=0.001). CONCLUSION: Our findings suggest that GPR65 is overexpressed in
      glioblastoma and its high expression predicts unfavorable clinical outcome for
      patients. Targeting GPR65 may serve as a potential therapy for treating
      glioblastoma.

PMID- 29223794
TI  - A new T2 lesion in a patient with the clinically isolated syndrome does not
      necessarily imply a conversion to multiple sclerosis.
AB  - In the follow-up of patients with the clinically isolated syndrome, both clinical
      and MRI findings should be carefully evaluated by clinicians to avoid
      misinterpretation and inappropriate diagnosis of multiple sclerosis. We describe
      a case of a patient with a previous diagnosis of clinically isolated syndrome who
      developed a new asymptomatic brain lesion at the MRI follow-up. The careful
      evaluation of clinical history and radiological findings allowed the correct
      diagnosis of cocaine-associated ischemic stroke. Our case highlights that, in
      patients with the clinically isolated syndrome, the appearance of a new lesion on
      MRI does not necessarily imply a conversion to multiple sclerosis. Among "better
      explanations", ischemic lesions are of relevance and, in patients without typical
      risk factors for stroke, rarer causes such as cocaine assumption should be
      considered.

PMID- 29223795
TI  - Good distractions: Testing the effects of listening to an audiobook on driving
      performance in simple and complex road environments.
AB  - Distracted driving (driving while performing a secondary task) causes many
      collisions. Most research on distracted driving has focused on operating a cell
      phone, but distracted driving can include eating while driving, conversing with
      passengers or listening to music or audiobooks. Although the research has focused
      on the deleterious effects of distraction, there may be situations where
      distraction improves driving performance. Fatigue and boredom are also associated
      with collision risk and it is possible that secondary tasks can help alleviate
      the effects of fatigue and boredom. Furthermore, it has been found that
      individuals with high levels of executive functioning as measured by the OSPAN
      (Operation Span) task show better driving while multitasking. In this study,
      licensed drivers were tested in a driving simulator (a car body surrounded by
      screens) that simulated simple or complex roads. Road complexity was manipulated
      by increasing traffic, scenery, and the number of curves in the drive.
      Participants either drove, or drove while listening to an audiobook. Driving
      performance was measured in terms of braking response time to hazards (HRT): the
      time required to brake in response to pedestrians or vehicles that suddenly
      emerged from the periphery into the path of the vehicle, speed, standard
      deviation of speed, standard deviation of lateral position (SDLP). Overall,
      braking times to hazards were higher on the complex drive than the simple one,
      though the effects of secondary tasks such as audiobooks were especially
      deleterious on the complex drive. In contrast, on the simple drive, driving while
      listening to an audiobook lead to faster HRT. We found evidence that individuals
      with high OSPAN scores had faster HRTs when listening to an audiobook. These
      results suggest that there are environmental and individual factors behind
      difference in the allocation of attention while listening to audiobooks while
      driving.

PMID- 29223796
TI  - Species specific RNA A-to-I editing of mosquito RDL modulates GABA potency and
      influences agonistic, potentiating and antagonistic actions of ivermectin.
AB  - The insect GABA receptor, RDL, is the target of several classes of pesticides.
      The peptide sequences of RDL are generally highly conserved between diverse
      insects. However, RNA A-to-I editing can effectively alter amino acid residues of
      RDL in a species specific manner, which can affect the potency of GABA and
      possibly insecticides. We report here that RNA A-to-I editing alters the gene
      products of Rdl in three mosquito disease vectors, recoding five amino acid
      residues in RDL of Aedes aegypti and six residues in RDLs of Anopheles gambiae
      and Culex pipiens, which is the highest extent of editing in RDL observed to
      date. Analysis of An. gambiae Rdl cDNA sequences identified 24 editing isoforms
      demonstrating a considerable increase in gene product diversity. RNA editing
      influenced the potency of the neurotransmitter, GABA, on An. gambiae RDL editing
      isoforms expressed in Xenopus laevis oocytes, as demonstrated by EC50s ranging
      from 5 +/- 1 to 246 +/- 41 MUM. Fipronil showed similar potency on different
      editing isoforms, with IC50s ranging from 0.18 +/- 0.08 to 0.43 +/- 0.09 MUM. In
      contrast, editing of An. gambiae RDL affected the activating, potentiating and
      inhibiting actions of ivermectin. For example, ivermectin potentiated currents
      induced by GABA at the EC20 concentration in the unedited isoform but not in the
      fully edited variant. Editing of a residue in the first transmembrane domain or
      the cys-loop influenced this potentiation, highlighting residues involved in the
      allosteric mechanisms of cys-loop ligand-gated ion channels. Understanding the
      interactions of ivermectin with molecular targets may have relevance to mosquito
      control in areas where people are administered with ivermectin to treat parasitic
      diseases.

PMID- 29223797
TI  - Clinical impact of adjuvant radiation therapy delay after neoadjuvant
      chemotherapy in locally advanced breast cancer.
AB  - BACKGROUND: and Purpose: Post-operative radiation therapy (PORT) is usually
      indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy
      (NAC) and surgery. However, the optimal timing to initiation of PORT is currently
      unknown. MATERIAL AND METHODS: We retrospectively evaluated data from patients
      with BC who received PORT after NAC and surgery at our institution from 2008 to
      2014. Patients were categorized into three groups according to the time between
      surgery and PORT: <8 weeks, 8-16 weeks and >16 weeks. RESULTS: A total of 581
      patients were included; 74% had clinical stage III. Forty-three patients started
      PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from
      surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks
      after surgery was associated with better disease-free survival (DFS) (<8 weeks
      versus 8-16 weeks: HR 0.33; 95% CI 0.13-0.81; p = 0.02; <8 weeks versus >16
      weeks: HR 0.38; 95% CI 0.15-0.96; p = 0.04) and better overall survival (OS) (<8
      weeks versus 8-16 weeks: HR 0.22; 95% CI 0.05-0.90; p = 0.036; <8 weeks versus
      >16 weeks: HR 0.28; 95% CI 0.07-1.15; p = 0.08). CONCLUSION: PORT started up to 8
      weeks after surgery was associated with better DFS and OS in locally-advanced BC
      patients submitted to NAC. Our findings suggest that early initiation of PORT is
      critically important for these patients. However, the low numbers of patients and
      events in this study prevent us from drawing firm conclusions.

PMID- 29223798
TI  - Self-reported volitional control in adolescents and young adults from a community
      cohort: Associations with current, past and future mental disorders.
AB  - Alterations in volitional control have been found for various mental disorders.
      However, it remains unclear to which degree such alterations vary by type of
      psychopathology and constitute preceding vulnerabilities or correlates of mental
      disorders. DSM-IV mental disorders were assessed among adolescents and young
      adults from the community at baseline (age 14-24) and in up to 3 follow-up
      assessments over 10 years (n = 2515) using a standardized diagnostic interview
      (DIA-X/M-CIDI). Self-reported volitional control was assessed at second follow-up
      (T2) when subjects were aged 17-28 using the German version of the Short Form of
      the Volitional Components Inventory. Linear regressions adjusted for sex, age and
      lifetime disorders revealed that anxiety and affective disorders were associated
      with widespread alterations in self-reported volitional control (lower self
      regulation, higher self inhibition and volitional inhibition), while substance
      use disorders were specifically associated with higher volitional inhibition.
      Logistic regressions adjusted for sex, age and prior lifetime psychopathology
      revealed that lower self-reported volitional control at T2 predicted incident
      panic, social phobia and substance use at T3 (follow-up interval M = 4.8 years).
      Findings point toward at least partly disorder-specific alterations in volitional
      control in mental disorders, which might be antecedent vulnerability factors and
      thus useful to guide early recognition and prevention.

PMID- 29223799
TI  - Association between housing, personal capacity factors and community
      participation among persons with psychiatric disabilities.
AB  - There is a need to understand which housing and personal capacity factors
      facilitate and hinder maximum community participation among people with
      psychiatric disabilities. The present study examined housing and personal
      capacity factors associated with community participation in a large sample of
      persons with psychiatric disabilities living in the same neighborhoods (defined
      by specified zip codes). Three hundred and forty-three persons with psychiatric
      disabilities were recruited from congregate and independent scatter-site housing
      programs in 3 New York City-area neighborhoods with high concentrations of
      housing for persons with psychiatric disabilities. Participants completed
      measures of community participation, psychiatric symptoms, substance use,
      independent living-skill, self-efficacy, and coping style. Community
      participation measures grouped into 3 factors: social community participation,
      physical community participation, and vocational involvement. Social community
      participation was associated with negative symptoms and active coping, but not by
      housing. Independent living-skill moderated the relationship between independent
      scatter-site housing and social community participation. Physical community
      participation was associated with negative symptoms, active coping, independent
      living-skill, and residence in independent scatter-site housing. Vocational
      involvement was only associated with negative symptoms. Findings suggest that a
      complex array of personal capacity and housing factors are associated with
      community participation among persons with psychiatric disabilities.

PMID- 29223800
TI  - Total and differential white blood cell counts and hemodynamic parameters in
      first-episode psychosis.
AB  - There is evidence for blood inflammatory abnormalities in patients with first
      episode psychosis (FEP). The monocyte- and neutrophil-to-lymphocyte ratios (MLR;
      NLR) are markers of inflammation and endothelial dysfunction, and predictors of
      cardiovascular disease, the leading cause of death in schizophrenia. We
      investigated relationships between white blood cell (WBC) counts and hemodynamic
      parameters associated with cardiovascular disease risk in 25 subjects age 18-50
      hospitalized for FEP and 44 controls. Subjects had a blood draw, vital signs, and
      medical history. Patients with FEP had significantly higher NLR, MLR, pulse
      pressure, and rate pressure product (RPP) than controls (p < 0.05 for each),
      after controlling for potential confounders. In linear regression analyses,
      higher monocytes were a significant predictor of higher pulse pressure (p =
      0.033) and higher MLR predicted RPP at the trend level (p = 0.051) in FEP, after
      controlling for potential confounders. To our knowledge, ours is the first report
      of increased RPP, a measure of myocardial workload, in FEP. We also replicated
      findings of increased NLR, MLR and pulse pressure in FEP. Our findings underscore
      that measurement of routine vital signs and blood total and differential WBC
      counts are germane to the clinical care of patients with psychosis as markers of
      cardiovascular disease risk.

PMID- 29223801
TI  - The external face of Candida albicans: A proteomic view of the cell surface and
      the extracellular environment.
AB  - : The cell surface and secreted proteins are the initial points of contact
      between Candida albicans and the host. Improvements in protein extraction
      approaches and mass spectrometers have allowed researchers to obtain a
      comprehensive knowledge of these external subproteomes. In this paper, we review
      the published proteomic studies that have examined C. albicans extracellular
      proteins, including the cell surface proteins or surfome and the secreted
      proteins or secretome. The use of different approaches to isolate cell wall and
      cell surface proteins, such as fractionation approaches or cell shaving, have
      resulted in different outcomes. Proteins with N-terminal signal peptide, known as
      classically secreted proteins, and those that lack the signal peptide, known as
      unconventionally secreted proteins, have been consistently identified. Existing
      studies on C. albicans extracellular vesicles reveal that they are relevant as an
      unconventional pathway of protein secretion and can help explain the presence of
      proteins without a signal peptide, including some moonlighting proteins, in the
      cell wall and the extracellular environment. According to the global view
      presented in this review, cell wall proteins, virulence factors such as adhesins
      or hydrolytic enzymes, metabolic enzymes and stress related-proteins are
      important groups of proteins in C. albicans surfome and secretome. BIOLOGICAL
      SIGNIFICANCE: Candida albicans extracellular proteins are involved in biofilm
      formation, cell nutrient acquisition and cell wall integrity maintenance.
      Furthermore, these proteins include virulence factors and immunogenic proteins.
      This review is of outstanding interest, not only because it extends knowledge of
      the C. albicans surface and extracellular proteins that could be related with
      pathogenesis, but also because it presents insights that may facilitate the
      future development of new antifungal drugs and vaccines and contributes to
      efforts to identify new biomarkers that can be employed to diagnose candidiasis.
      Here, we list more than 570 C. albicans proteins that have been identified in
      extracellular locations to deliver the most extensive catalogue of this type of
      proteins to date. Moreover, we describe 16 proteins detected at all locations
      analysed in the works revised. These proteins include the
      glycophosphatidylinositol (GPI)-anchored proteins Ecm33, Pga4 and Phr2 and
      unconventional secretory proteins such as Eft2, Eno1, Hsp70, Pdc11, Pgk1 and
      Tdh3. Furthermore, 13 of these 16 proteins are immunogenic and could represent a
      set of interesting candidates for biomarker discovery.

PMID- 29223802
TI  - Proteogenomic insights into uranium tolerance of a Chernobyl's Microbacterium
      bacterial isolate.
AB  - : Microbacterium oleivorans A9 is a uranium-tolerant actinobacteria isolated from
      the trench T22 located near the Chernobyl nuclear power plant. This site is
      contaminated with different radionuclides including uranium. To observe the
      molecular changes at the proteome level occurring in this strain upon uranyl
      exposure and understand molecular mechanisms explaining its uranium tolerance, we
      established its draft genome and used this raw information to perform an in-depth
      proteogenomics study. High-throughput proteomics were performed on cells exposed
      or not to 10MUM uranyl nitrate sampled at three previously identified phases of
      uranyl tolerance. We experimentally detected and annotated 1532 proteins and
      highlighted a total of 591 proteins for which abundances were significantly
      differing between conditions. Notably, proteins involved in phosphate and iron
      metabolisms show high dynamics. A large ratio of proteins more abundant upon
      uranyl stress, are distant from functionally-annotated known proteins,
      highlighting the lack of fundamental knowledge regarding numerous key molecular
      players from soil bacteria. BIOLOGICAL SIGNIFICANCE: Microbacterium oleivorans A9
      is an interesting environmental model to understand biological processes engaged
      in tolerance to radionuclides. Using an innovative proteogenomics approach, we
      explored its molecular mechanisms involved in uranium tolerance. We sequenced its
      genome, interpreted high-throughput proteomic data against a six-reading frame
      ORF database deduced from the draft genome, annotated the identified proteins and
      compared protein abundances from cells exposed or not to uranyl stress after a
      cascade search. These data show that a complex cellular response to uranium
      occurs in Microbacterium oleivorans A9, where one third of the experimental
      proteome is modified. In particular, the uranyl stress perturbed the phosphate
      and iron metabolic pathways. Furthermore, several transporters have been
      identified to be specifically associated to uranyl stress, paving the way to the
      development of biotechnological tools for uranium decontamination.

PMID- 29223803
TI  - Fine electron biprism on a Si-on-insulator chip for off-axis electron holography.
AB  - Off-axis electron holography allows both the amplitude and the phase shift of an
      electron wavefield propagating through a specimen in a transmission electron
      microscope to be recovered. The technique requires the use of an electron biprism
      to deflect an object wave and a reference wave to form an interference pattern.
      Here, we introduce an approach based on semiconductor processing technology to
      fabricate fine electron biprisms with rectangular cross-sections. By performing
      electrostatic calculations and preliminary experiments, we demonstrate that such
      biprisms promise improved performance for electron holography experiments.

PMID- 29223804
TI  - Oxindole based oxadiazole hybrid analogs: Novel alpha-glucosidase inhibitors.
AB  - Inhibition of alpha-glucosidase is an effective strategy for controlling post
      prandial hyperglycemia in diabetic patients. Beside these alpha-glucosidase
      inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in
      view the greater importance of alpha-glucosidase inhibitors here in this study we
      are presenting oxindole based oxadiazoles hybrid analogs (1-20) synthesis,
      characterized by different spectroscopic techniques including 1H NMR and EI-MS
      and their alpha-glucosidase inhibitory activity. All compounds were found potent
      inhibitors for the enzyme with IC50 values ranging between 1.25 +/- 0.05 and
      268.36 +/- 4.22 uM when compared with the standard drug acarbose having IC50
      value 895.09 +/- 2.04 uM. Our study identifies novel series of potent alpha
      glucosidase inhibitors and further investigation on this may led to the lead
      compounds. A structure activity relationship has been established for all
      compounds. The interactions of the active compounds and enzyme active site were
      established with the help of molecular docking studies.

PMID- 29223805
TI  - Development of pyrrolo[2,1-c][1,4]benzodiazepine beta-glucoside prodrugs for
      selective therapy of cancer.
AB  - Cancer chemotherapy has several limitations such as often insufficient
      differentiation between malign tissue and benign tissue. The clinical utility of
      the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are inadequate because of the lack
      of selectivity for tumor tissues, high reactivity of the pharmacophoric imine
      functionality, low water solubility, and stability. To address these limitations
      two new beta-glucoside prodrugs of PBDs have been synthesized and evaluated for
      their potential use in selective therapy of solid tumors by ADEPT. The
      preliminary studies reveal the prodrugs are much less toxic compared to the
      parent moieties. These prodrugs are activated by beta-glucosidase to produce the
      active cytotoxic moiety signifying their utility in ADEPT of cancer. The prodrugs
      1a and 1b were evaluated for their cytotoxic activity in three human cancer cell
      lines, i.e., A375, MCF-7 and HT-29 by employing MTT assay. The results reveal
      that the prodrugs have shown significant cytotoxic activity in the presence of
      enzyme. Another important property of these molecules is their enhanced water
      solubility and stability, which are essential for a molecule to be an effective
      drug.

PMID- 29223806
TI  - Preventing the N-terminal processing of human interferon alpha-2b and its
      chimeric derivatives expressed in Escherichia coli.
AB  - We have previously shown that human interferon alpha-2b (IFN) produced in
      Escherichia coli (E. coli) is heterogeneous at the N-terminal, with three major
      species (Ahsan et al., 2014). These are: (a) the direct translation product of
      the gene retaining the N-terminal methionine, (b) a species from which the
      methionyl residue has been removed by E. coli methionyl aminopeptidase to give
      the native interferon alpha-2b and (c) in which the N-terminal Cys residue of the
      latter contains an acetyl group. In this paper we overcome this heterogeneity,
      using engineered interferon derivatives with phenylalanine residue directly
      downstream of the N-terminal methionine (Met-Phe-IFN). This modification not only
      prevented the removal of the N-terminal methionine by E. coli methionyl
      aminopeptidase but also the subsequent N-acetylation. Critically, Met-Phe-IFN had
      enhanced activity in a biological assay. N-terminal stabilization was also
      achieved by fusing human cytochrome b5 at the N-terminal of interferon (b5-IFN
      chimera). In this case also, the protein was more active than a reciprocal
      chimera with cytochrome b5 at the C-terminal of interferon (Met-IFN-b5-chimera).
      This latter protein also had a heterogeneous N-terminal but addition of
      phenylalanine following Met, (Met-Phe-IFN-b5-chimera), resolved this problem and
      gave enhanced biological activity.

PMID- 29223807
TI  - Design, synthesis, and biological evaluation of deuterated phenylpropionic acid
      derivatives as potent and long-acting free fatty acid receptor 1 agonists.
AB  - The free fatty acid receptor 1 (FFA1) is a potential target due to its function
      in enhancement of glucose-stimulated insulin secretion. Takeda's compound 1 has
      robustly in vitro activity for FFA1, but it has been suffered from poor
      pharmacokinetic (PK) profiles because the phenylpropanoic acid is vulnerable to
      beta-oxidation. To identify orally available agonists, we tried to interdict the
      metabolically labile group by incorporating two deuterium atoms at the alpha
      position of phenylpropionic acid. Interestingly, the differences of
      physicochemical properties between hydrogen and deuterium are quite small, but
      there are many differences in the structure-activity relationship between
      phenylpropionic acid series and present deuterated series. Further optimizations
      of deuterated series led to the discovery of compound 18, which exhibited a
      superior balance in terms of in vitro activity, lipophilicity, and solubility.
      Better still, compound 18 revealed a lower clearance (CL = 0.44 L/h/kg), higher
      maximum concentration (Cmax = 7584.27 MUg/L), and longer half-life (T1/2 = 4.16
      h), resulting in a >23-fold exposure than compound 1. In subsequent in vivo
      pharmacodynamic studies, compound 18 showed a robustly glucose-lowering effect in
      rodent without the risk of hypoglycemia.

PMID- 29223808
TI  - Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight
      gain and growth.
AB  - We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the
      time of delivery are associated with birth outcome and if early life exposure (in
      utero/nursing) is associated with early childhood growth and weight gain.
      Maternal PFAA body burdens were estimated by analysis of serum samples from
      mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after
      delivery between 1996 and 2011. Data on child length and weight were collected
      from medical records and converted into standard deviation scores (SDS). Multiple
      linear regression models with appropriate covariates were used to analyze
      associations between maternal PFAA levels and birth outcomes (n=381). After birth
      Generalized Least Squares models were used to analyze associations between
      maternal PFAA and child growth (n=200). Inverse associations were found between
      maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA),
      and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of 
      0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA.
      After birth, weight and length SDS were not significantly associated with
      maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and
      PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal,
      these associations suggest that PFAA affects fetal and childhood body development
      in different directions.

PMID- 29223809
TI  - Cadmium induces BNIP3-dependent autophagy in chicken spleen by modulating miR-33
      AMPK axis.
AB  - Cadmium (Cd), a widespread environmental pollutant, has toxic effects on organs
      including spleen. However, the underlying mechanisms of Cd induced spleen
      toxicity and the roles of micro-RNA (miRNA) in this process remain poorly
      understood. To investigate this, cadmium chloride (CdCl2, 10 mg/kg) was
      administered in the diet of chickens for 90 days. Electron microscopy, qPCR and
      Western blot were performed. Results showed that Cd exposure suppressed miR-33-5q
      which increased the levels of AMPK. Subsequently, significant decrease in
      AKT/mTOR signaling and HSP70 were observed. Concurrently, levels of NF-kappaB, p
      JNK/JNK increased significantly. Moreover, the expression of BNIP3 and other
      autophagy markers (LC3-I, LC3-II, Beclin-1) increased significantly.
      Additionally, the levels of ions (Ca, Cr, Se, Sr, Sn, Ba) and (Na, Mg, V, Fe, Mo,
      Cu, Zn, Cd) significantly decreased and increased, respectively. Taken together,
      we conclude that Cd induced the deregulation of miR-33-AMPK axis led to BNIP3
      dependent autophagy in chicken spleen through AKT/mTOR and HSP70-NF-kappaB/JNK
      signal pathways. In-addition Cd could affect ion homeostasis in chicken spleen.

PMID- 29223810
TI  - Response to the comments on ''Changes in activation energy and kinetics of heat
      activated persulfate oxidation of phenol in response to changes in pH and
      temperature'' by Ma, J., Li, H., Chi, L., Chen, H., & Chen, C. [Chemosphere 189
      (2017) 86-93].

PMID- 29223811
TI  - Predicting apparent singlet oxygen quantum yields of dissolved black carbon and
      humic substances using spectroscopic indices.
AB  - Dissolved black carbon (DBC) is ubiquitous in aquatic systems, being an important
      subgroup of the dissolved organic matter (DOM) pool. Nevertheless, its aquatic
      photoactivity remains largely unknown. In this study, a range of spectroscopic
      indices of DBC and humic substance (HS) samples were determined using UV-Vis
      spectroscopy, fluorescence spectroscopy, and proton nuclear magnetic resonance.
      DBC can be readily differentiated from HS using spectroscopic indices. It has
      lower average molecular weight, but higher aromaticity and lignin content. The
      apparent singlet oxygen quantum yield (Phisinglet oxygen) of DBC under simulated
      sunlight varies from 3.46% to 6.13%, significantly higher than HS, 1.26%-3.57%,
      suggesting that DBC is the more photoactive component in the DOM pool. Despite
      drastically different formation processes and structural properties, the
      Phisinglet oxygen of DBC and HS can be well predicted by the same simple linear
      regression models using optical indices including spectral slope coefficient
      (S275-295) and absorbance ratio (E2/E3) which are proxies for the abundance of
      singlet oxygen sensitizers and for the significance of intramolecular charge
      transfer interactions. The regression models can be potentially used to assess
      the photoactivity of DOM at large scales with in situ water spectrophotometry or
      satellite remote sensing.

PMID- 29223812
TI  - Could saponins be used to enhance bioremediation of polycyclic aromatic
      hydrocarbons in aged-contaminated soils?
AB  - Polycyclic aromatic hydrocarbons (PAH) are persistent organic compounds of major
      concern that tend to accumulate in the environment, threatening ecosystems and
      health. Brownfields represent an important tank for PAHs and require remediation.
      Researches to develop bioremediation and phytoremediation techniques are being
      conducted as alternatives to environmentally aggressive, expensive and often
      disruptive soil remediation strategies. The objectives of the present study were
      to investigate the potential of saponins (natural surfactants) as extracting
      agents and as bioremediation enhancers on an aged-contaminated soil. Two
      experiments were conducted on a brownfield soil containing 15 PAHs. In a first
      experiment, soil samples were extracted with saponins solutions (0; 1; 2; 4 and 8
      g.L-1). In a second experiment conducted in microcosms (28  degrees C), soil
      samples were incubated for 14 or 28 days in presence of saponins (0; 2.5 and 5 mg
      g-1). CO2 emissions were monitored throughout the experiment. After the
      incubation, dehydrogenase activity was measured as an indicator of
      microbiological activity and residual PAHs were determined. In both experiments
      PAHs were determined using High-Performance Liquid Chromatography and
      Fluorimetric Detection. The 4 g.L-1 saponins solution extracted significantly
      more acenaphtene, fluorene, phenanthrene, anthracene, and pyrene than water. PAHs
      remediation was not enhanced in presence of saponins compared to control samples
      after 28 days. However CO2 emissions and dehydrogenase activities were
      significantly more important in presence of saponins, suggesting no toxic effect
      of these surfactants towards soil microbiota.

PMID- 29223813
TI  - Facile and eco-friendly fabrication of AgNPs coated silk for antibacterial and
      antioxidant textiles using honeysuckle extract.
AB  - Recently, there is a growing trend towards the functionalization of silk through
      nanotechnology for the prevention of fiber damage from microbial attack and the
      enhancement of hygienic aspects. Considering sustainable development and
      environmental protection, the eco-friendly fabrication of silver nanoparticles
      (AgNPs)-modified silk using natural extracts has currently become a hot research
      area. This study presents a facile strategy for the fabrication of colorful and
      multifunctional silk fabric using biogenic AgNPs prepared by honeysuckle extract
      as natural reductant and stabilizing agents. The influences of pH and reactant
      concentrations on the AgNPs synthesis were investigated. The color
      characteristics and functionalities of AgNPs treated silk were evaluated. The
      results revealed that the particle size of AgNPs decreased with increasing pH.
      The diameter of AgNPs decreased with increasing amount of honeysuckle extract and
      reducing amount of silver nitrate. The transmission electron microscopy image
      showed that the AgNPs were spherical in shape with a narrow size distribution.
      The treated silk showed excellent antibacterial activities against E. coli and S.
      aureus, and certain antioxidant activity. Both of the antibacterial and
      antioxidant activities were well maintained even after 30 washing cycles. This
      work provides a sustainable and eco-friendly approach to the fabrication of AgNPs
      coated silk for colorful and long-term multifunctional textiles using honeysuckle
      extract.

PMID- 29223814
TI  - A metabolomics strategy to assess the combined toxicity of polycyclic aromatic
      hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs).
AB  - The combined toxicity of mixed chemicals is usually evaluated according to
      several specific endpoints, and other potentially toxic effects are disregarded.
      In this study, we provided a metabolomics strategy to achieve a comprehensive
      understanding of toxicological interactions between mixed chemicals on
      metabolism. The metabolic changes were quantified by a pseudotargeted analysis,
      and the types of combined effects were quantitatively discriminated according to
      the calculation of metabolic effect level index (MELI). The metabolomics strategy
      was used to assess the combined effects of polycyclic aromatic hydrocarbons
      (PAHs) and short-chain chlorinated paraffins (SCCPs) on the metabolism of human
      hepatoma HepG2 cells. Our data suggested that exposure to a combination of PAHs
      and SCCPs at human internal exposure levels could result in an additive effect on
      the overall metabolism, whereas diverse joint effects were observed on various
      metabolic pathways. The combined exposure could induce a synergistic up
      regulation of phospholipid metabolism, an additive up-regulation of fatty acid
      metabolism, an additive down-regulation of tricarboxylic acid cycle and
      glycolysis, and an antagonistic effect on purine metabolism. SCCPs in the mixture
      acted as the primary driver for the acceleration of phospholipid and fatty acid
      metabolism. Lipid metabolism disorder caused by exposure to a combination of PAHs
      and SCCPs should be an important concern for human health.

PMID- 29223815
TI  - Attenuation of bacterial cytotoxicity of carbon nanotubes by riverine suspended
      solids in water.
AB  - The impact of solid particles on ecotoxicity of nanomaterials in water
      environments is poorly understood. This study investigated the effect of natural
      riverine suspended solids (SPS) on the cytotoxicity of single-walled carbon
      nanotubes (SWCNTs) towards a bacterium, Ochrobactrum sp. in water. Compared with
      SWCNT suspension without SPS, the presence of SPS at different concentrations
      ranging from 20 to 400 mg L-1 markedly increased the survival rates of bacteria
      exposed to 50 mg L-1 SWCNTs and bacterial survival rates increased with SPS
      concentrations by a power law. Sedimentation experiments and field emission
      scanning electron microscopy revealed the occurrence of heteroaggregation between
      SWCNTs and SPS, probably responsible for the reduced SWCNT toxicity. Furthermore,
      the extended Derjaguin-Landau-Verwey-Overbeek (ExDLVO) calculation showed the
      mitigated toxicity might also result from the decreased SWCNT-bacterium
      interaction energy with the increased SPS concentrations and the stronger SPS
      SWCNT interaction than the SWCNT-bacterium interaction. This work provides new
      insights into our understanding of environmental hazards of engineered
      nanomaterials in aquatic systems.

PMID- 29223816
TI  - Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure
      via drinking water.
AB  - The neurotoxicity of arsenic is a serious health problem, especially for
      children. DNA epigenetic change may be an important pathogenic mechanism, but the
      molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly
      (SD) rats were treated with arsenic trioxide via drinking water for 6 months,
      simulating real developmental exposure situation of children. Arsenic exposure
      impaired the cognitive abilities, and altered the expression of neuronal activity
      regulated genes. Total arsenic concentrations of cortex and hippocampus tissues
      were significantly increased in a dose-dependent manner. The reduction in 5
      methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the
      down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations
      (TETs) expression suggested that DNA methylation/demethylation processes were
      significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level
      wasn't changed, but the expression of the important indicators of oxidative/anti
      oxidative balance and tricarboxylic acid (TCA) cycle was significantly
      deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance,
      further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (alpha
      KG) pathway, and consequently cause DNA methylation/demethylation disruption. The
      present study implies oxidative stress but not SAM depletion may lead to DNA
      epigenetic alteration and arsenic neurotoxicity.

PMID- 29223817
TI  - Elevated inflammatory Lp-PLA2 and IL-6 link e-waste Pb toxicity to cardiovascular
      risk factors in preschool children.
AB  - Cardiovascular toxicity of lead (Pb) manifests primarily as an effect on blood
      pressure and eventual increased risk of atherosclerosis and cardiovascular
      events. Therefore, we investigated vascular inflammatory biomarkers and
      cardiovascular effects of Pb-exposed children. A total of 590 children (3-7 years
      old) were recruited from Guiyu (n = 337), an electronic waste (e-waste)-exposed
      group, and Haojiang (n = 253), a reference group, from November to December 2016.
      We measured child blood Pb levels (BPbs), and systolic and diastolic blood
      pressure. Pulse pressure was calculated for the latter two. Serum biomarkers
      including lipid profiles and inflammatory cytokines, and plasma lipoprotein
      associated phospholipase A2 (Lp-PLA2) were detected. Unadjusted regression
      analysis illustrated that higher ln-transformed BPb associated with lower
      systolic blood pressure and pulse pressure. After adjustment for various
      confounders, the relational degree of lnBPb and blood pressure measures became
      slightly attenuated or not significant. Elevated BPb was associated with higher
      Lp-PLA2, interleukin (IL)-6, triglycerides (TG) and lower high-density
      lipoprotein (HDL). Lp-PLA2 remained inversely associated with pulse pressure and
      HDL, but positively with ratios of total cholesterol to HDL (Tc/HDL) and low
      density lipoprotein to HDL (LDL/HDL). IL-6 was associated negatively with
      systolic blood pressure, pulse pressure and HDL, and positively associated with
      TG, Tc/HDL and LDL/HDL. The mediation effect of biomarkers on the association of
      BPb with pulse pressure was insignificant except for Lp-PLA2. Available data
      supports the conclusion that e-waste-exposed children with higher BPbs and
      concomitant abnormal measures of cardiovascular physiology have an augmented
      prevalence of vascular inflammation, as well as lipid disorder.

PMID- 29223818
TI  - Application of airborne photogrammetry for the visualisation and assessment of
      contamination migration arising from a Fukushima waste storage facility.
AB  - Airborne systems such as lightweight and highly portable unmanned aerial vehicles
      (UAVs) are becoming increasingly widespread in both academia and industry - with
      an ever-increasing range of applications, including (but not limited to), air
      quality sampling, wildlife monitoring and land-use mapping. In this work, high
      resolution airborne photogrammetry obtained using a multi-rotor system operating
      at low survey altitudes, is combined with ground-based radiation mapping data
      acquired at an interim storage facility for wastes removed as part of the large
      scale Fukushima clean-up program. The investigation aimed to assess the extent to
      which the remediation program at a specific site has contained the stored
      contaminants, as well as present a new methodology for rapidly surveying
      radiological sites globally. From the three-dimensional rendering of the site of
      interest, it was possible to not only generate a powerful graphic confirming the
      elevated radiological intensity existing at the location of the waste bags, but
      also to also illustrate the downslope movement of contamination due to species
      leakage from the large 1m3 storage bags. The entire survey took less than 1 h to
      perform, and was subsequently post-processed using graphical information software
      to obtain the renderings. The conclusions within this study not only highlight
      the usefulness of incorporating three-dimensional renderings within radiation
      mapping protocols, but also conclude that current methods of monitoring these
      storage facilities in the long term could be improved through the integration of
      UAVs within the standard protocol.

PMID- 29223819
TI  - Global occurrence of polybrominated diphenyl ethers and their hydroxylated and
      methoxylated structural analogues in an important animal feed (fishmeal).
AB  - Polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH) and
      methoxylated (MeO) structural analogues have been found widely distributed in
      aquatic ecosystems, and may exhibit potential adverse effects to humans due to
      their bioaccumulative behavior through food chain. Fishmeal is an important
      animal feed applied around the world and is generally of marine origin. However,
      the levels and sources of PBDEs in fishmeal have not been thoroughly evaluated
      and their structural analogues have not been reported to date. The present study
      collected ninety-two fishmeal samples from world main fishmeal producing area to
      determine 27 PBDEs, 10 MeO-PBDEs and 11 OH-PBDEs. The concentrations of
      Sigma27PBDEs, Sigma10MeO-PBDEs and Sigma11OH-PBDEs were in the ranges of 0.1-1498
      (mean: 75.8), 1.14-881 (37.4) and 1.00-47.5 (8.17) ng/g lipid, respectively.
      PBDEs were found primarily correlated with the historically commercial
      production, meaning higher production of certain commercial product in a country,
      higher corresponding PBDE congeners in local fishmeal. A market shift from penta-
      and octa-formulations toward deca-formulation was observed. BDE209 was identified
      as a major congener in fishmeal. Both the MeO-PBDEs and the OH-PBDEs were
      influenced by fishmeal producing areas (p < 0.001). High MeO-PBDEs were
      identified in the Southeast Asian fishmeal, which might be due to the suitable
      environmental conditions for the generation of bromoperoxidase-contained algae in
      local area. The ratio of two major MeO-PBDE congeners, 6-MeO-BDE47/2'-MeO-BDE68,
      were generally >1 in the northern hemisphere and <1 in the southern hemisphere in
      the present study, which was consistent with the results obtained from previous
      published papers. Both MeO-PBDEs and OH-PBDEs were in accordance with the
      specialties of naturally produced halogenated compounds.

PMID- 29223820
TI  - Arsenic mobility and characterization in lakes impacted by gold ore roasting,
      Yellowknife, NWT, Canada.
AB  - The controls on the mobility and fate of arsenic in lakes impacted by historical
      gold ore roasting in northern Canada have been examined. A detailed
      characterization of arsenic solid and aqueous phases in lake waters, lake
      sediments and sediment porewaters as well as surrounding soils was conducted in
      three small lakes (<200ha) downwind and within 5 km of the historic mining and
      roasting operations of Giant Mine (Northwest Territories). These lakes are marked
      by differing limnological characteristics such as area, depth and organic
      content. Radiometric age-dating shows that the occurrence of arsenic trioxide in
      lake sediments coincides with the regional onset of roasting activities.
      Quantification by advanced electron microscopy shows that arsenic trioxide
      accounts for up to 6 wt% of the total arsenic in sediments. The bulk (>80 wt%) of
      arsenic is contained in the form of secondary sulphide precipitates, with iron
      oxy-hydroxides hosting a minimal amount of arsenic (<1 wt%). Soluble arsenic
      trioxide particles act as the primary source of arsenic into sediment porewaters.
      Dissolved arsenic in reducing porewaters both precipitates in-situ as secondary
      sulphides, and diffuses upwards into the overlying lake waters. Geogenic arsenic
      phases are present in sediments in low concentrations and are not considered a
      significant source of arsenic to porewaters or lake waters. Sediment-water
      interface diffusive flux calculations suggest that the diffusion of dissolved
      arsenic from porewaters, combined with lake water residence time, are the
      predominant mechanisms controlling arsenic concentrations in lake waters.

PMID- 29223822
TI  - Exposure to acrylamide induces cardiac developmental toxicity in zebrafish during
      cardiogenesis.
AB  - Acrylamide (AA), an environmental pollutant, has been linked to neurotoxicity,
      genotoxicity and carcinogenicity. AA is widely used to synthesize polymers for
      industrial applications, is widely found in Western-style carbohydrate-rich foods
      and cigarette smoke, and can also be detected in human umbilical cord blood and
      breast milk. This is the first study that demonstrated the cardiac developmental
      toxicity of AA in zebrafish embryos. Post-fertilization exposure to AA caused a
      clearly deficient cardiovascular system with a shrunken heart and abortive
      morphogenesis and function. Disordered expression of the cardiac genes, myl7,
      vmhc, myh6, bmp4, tbx2b and notch1b, as well as reduced number of myocardial
      cells and endocardial cells, indicated the collapsed development of ventricle and
      atrium and failed differentiation of atrioventricular canal (AVC). Although cell
      apoptosis was not affected, the capacity of cardiomyocyte proliferation was
      significantly reduced by AA exposure after fertilization. Further investigation
      showed that treatment with AA specifically reduced the expressions of nkx2.5,
      myl7 and vmhc in the anterior lateral plate mesoderm (ALPM) during the early
      cardiogenesis. In addition, AA exposure disturbed the restricted expressions of
      bmp4, tbx2b and notch1b during atrioventricular (AV) valve development and
      cardiac chambers maturation. Our results showed that AA-induced cardiotoxicity
      was related to decreased cardiac progenitor genes expression, reduced myocardium
      growth, abnormal cardiac chambers morphogenesis and disordered AVC
      differentiation. Our study demonstrates that AA exposure during a time point
      analogous to the first trimester in humans has a detrimental effect on early
      heart development in zebrafish. A high ingestion rate of AA-containing products
      may be an underlying risk factor for cardiogenesis in fetuses.

PMID- 29223821
TI  - Germination, physiological and biochemical responses of acacia seedlings (Acacia
      raddiana and Acacia tortilis) to petroleum contaminated soils.
AB  - Along the arid Arava, southern Israel, acacia trees (Acacia raddiana and Acacia
      tortilis) are considered keystone species. Yet they are threatened by the ongoing
      aquifer depletion for agriculture, the conversion of natural land to agricultural
      land, seed infestation by bruchid beetles, and the reduction in precipitation
      level in the region. In the acacia dominated Evrona reserve (southern Arava),
      adding to these threats are recurrent oil spills from an underground pipeline. We
      report here a study of the effects of contaminated soils, from a recent (December
      2014) and a much older (1975) oil spills. The effects of local petroleum oil
      contaminated soils on germination and early growing stages of the two acacia
      species were studied by comparisons with uncontaminated (control) soils from the
      same sites. For both acacia species, germination was significantly reduced in the
      2014 oil-contaminated soils, whereas delayed in the 1975 oil-contaminated soil.
      There was no significant effect of oil volatile compounds on seed germination. At
      105 days post transplanting (DPT), height, leaf number, stem diameter, and root
      growth were significantly smaller in the oil-contaminated soils. While
      photosynthetic performance (quantum yield of photosystem II) did not differ
      considerably between treatments, reductions of chlorophylls content and protein
      content were found in seedlings growing in the contaminated soils. Significant
      increases in superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities
      were found in roots of seedlings growing in oil-contaminated soils. These results
      demonstrate that seed germination and seedling growth of both acacia species were
      strongly restricted by oil contamination in soils, from both recent (2014) and a
      40-year old (1975) oil spills. Such long-term effects of oil spills on local
      acacia seedlings could shift the structure of local acacia communities. These
      results should be taken into account by local authorities aiming to clean up and
      restore such polluted areas.

PMID- 29223823
TI  - The effect of reducing EEG electrode number on the visual interpretation of the
      human expert for neonatal seizure detection.
AB  - OBJECTIVES: To measure changes in the visual interpretation of the EEG by the
      human expert for neonatal seizure detection when reducing the number of recording
      electrodes. METHODS: EEGs were recorded from 45 infants admitted to the neonatal
      intensive care unit (NICU). Three experts annotated seizures in EEG montages
      derived from 19, 8 and 4 electrodes. Differences between annotations were
      assessed by comparing intra-montage with inter-montage agreement (K). RESULTS:
      Three experts annotated 4464 seizures across all infants and montages. The inter
      expert agreement was not significantly altered by the number of electrodes in the
      montage (p = 0.685, n = 43). Reducing the number of EEG electrodes altered the
      seizure annotation for all experts. Agreement between the 19-electrode montage
      (K19,19 = 0.832) was significantly higher than the agreement between 19 and 8
      electrode montages (dK = 0.114; p < 0.001, n = 42) or 19 and 4-electrode montages
      (dK = 0.113, p < 0.001, n = 43). Seizure burden and number were significantly
      underestimated by the 4 and 8-electrode montage (p < 0.001). No significant
      difference in agreement was found between 8 and 4-electrode montages (dK = 0.002;
      p = 0.07, n = 42). CONCLUSIONS: Reducing the number of EEG electrodes from 19
      electrodes resulted in slight but significant changes in seizure detection.
      SIGNIFICANCE: Four-electrode montages for routine EEG monitoring are comparable
      to eight electrodes for seizure detection in the NICU.

PMID- 29223824
TI  - Correlating motor unit morphology with bioelectrical activity - A simulation
      study.
AB  - OBJECTIVES: The aim was to determine motor unit morphology underpinning the
      various MUP waveforms using MUP analysis. METHOD: The simulation method is based
      on the decomposition of MUP into single fiber potentials. Number of fibers, fiber
      diameters and fiber to electrode distances were determined. The impact of each
      muscle fiber on the MUP waveform was determined and quantified by its percentage
      contribution. RESULTS: The origin of the four examined MUPs of distinct waveforms
      have been explained by showing the histograms of fiber diameters and their
      distance to the electrode. In the case of a low amplitude MUP it was found that
      it originated from fibers of smaller than normal diameters with no dominant
      fiber. In another case of a MUP of short duration its shape was due to a single
      fiber close to the electrode which contributed to about 80% of the MUP. In case
      of polyphasic MUP, muscle fiber diameters variability was responsible for MUP
      characteristic. MUP from normal muscle originated from few fibers of similar
      diameters. Correlation between MUP's characteristic and morphological features
      has been indicated. Our findings are consistent with the neurophysiological
      knowledge about the origins of MUP. The approximation method enables MUP analysis
      that provides quantitative description of motor unit morphology. CONCLUSION: MUP
      analysis using an approximation method enables to get an insight into motor unit
      morphology and therefore increases understanding of the way the motor unit
      structure correlates with MUP waveform. SIGNIFICANCE: Extending the amount of
      information available from EMG examinations.

PMID- 29223825
TI  - Theranostic liposomes as a bimodal carrier for magnetic resonance imaging
      contrast agent and photosensitizer.
AB  - The present study is focused on the development of liposomes bearing gadolinium
      chelate (GdLip) providing two functionalities for magnetic resonance imaging
      (MRI) and photodynamic therapy of cancer. A lipid derivative of gadolinium(III)
      diethylenetriamine pentaacetic acid salt (GdDTPA1) was inserted in the liposomal
      membrane and served as MRI contrast agent whereas a zinc phthalocyanine (ZnPc)
      was used as a model photosensitizer. In addition to conventional liposomes,
      pegylated lipids were used for the preparation of "stealth" liposomes. The
      characterization of different GdLip formulations involved evaluation of the
      liposomes size by nanoparticle tracking analysis, thermal phase behavior by
      differential scanning calorimetry and ZnPc-mediated singlet oxygen production.
      Furthermore, relaxivity measurements were performed as well as cytotoxicity and
      photodynamic activity against cancerous and normal cell lines was studied. Size
      and thermal behavior were only slightly influenced by GdLip composition, however
      it distinctly affected singlet oxygen production of ZnPc-loaded GdLip. The
      quantum yields of singlet oxygen generation by zinc phthalocyanine incorporated
      in GdLip containing cationic or/and pegylated lipids were smaller than those
      obtained for non-pegylated carriers with l-alpha-phosphatidylglycerol. In
      general, all formulations of GdLip, irrespectively of composition, were
      characterized by relaxivities higher than those of commercially used contrast
      agents (e.g. Magnevist(r)). NMR study has shown that the incorporation of ZnPc
      into the formulations of GdLip increases the relaxation parameters r1 and r2,
      compared to the values for the non-loaded vesicles. GdDTPA1 did not influence the
      photodynamic activity of ZnPc against HeLa cells.

PMID- 29223826
TI  - Modulation effect of double strand DNA on the self-assembly of N-terminal domain
      of Euplotes octocarinatus centrin.
AB  - Centrin is a member of the EF-hand super family of calcium-binding proteins,
      which can behave as a part of damage detector initiated the initiation of
      nucleotide excision repair (NER). Its self-assembly plays a causative role in
      fiber contraction associated with the cell division cycle and ciliogenesis. To
      explore the possible role of DNA in the process of centrin self-assembly, the
      aggregation properties of N-terminal domain of Euplotes octocarinatus centrin (N
      EoCen) in the presence of DNA with or without metal ions are investigated. It is
      verified that metal ions, such as Ca2+ and Tb3+, can bind to N-EoCen with 2:1
      stoichiometry by isothermal titration calorimetry (ITC). Importantly, this study
      reports that double strand DNA (dsDNA) is capable of binding N-EoCen, changing
      conformation of protein and modulating centrin aggregation, as demonstrated by
      extensive biophysical assays. Interestingly, the open conformation of protein
      induced by metal ions may be favour of the interaction of protein with dsDNA.
      Nevertheless, the randomly coiled single strand DNA (ssDNA) is completely
      inefficient to the aggregation regulation. Furthermore, results reveal that
      hydrophobic site could play important role in the process. This finding may link
      to the potent roles of centrin in the NER process.

PMID- 29223827
TI  - Colonic aberrant crypt formation accompanies an increase of opportunistic
      pathogenic bacteria in C57BL/6 mice fed a high-fat diet.
AB  - The increasing worldwide incidence of colon cancer has been linked to obesity and
      consumption of a high-fat Western diet. To test the hypothesis that a high-fat
      diet (HFD) promotes colonic aberrant crypt (AC) formation in a manner associated
      with gut bacterial dysbiosis, we examined the susceptibility to azoxymethane
      (AOM)-induced colonic AC and microbiome composition in C57/BL6 mice fed a
      modified AIN93G diet (AIN, 16% fat, energy) or an HFD (45% fat, energy) for 14
      weeks. Mice receiving the HFD exhibited increased plasma leptin, body weight,
      body fat composition and inflammatory cell infiltration in the ileum compared
      with those in the AIN group. Consistent with the gut inflammatory phenotype, we
      observed an increase in colonic AC, plasma interleukin-6, tumor necrosis factor
      alpha, monocyte chemoattractant protein-1 and inducible nitric oxide synthase in
      the ileum of the HFD-AOM group compared with the AIN-AOM group. Although the HFD
      and AIN groups did not differ in bacterial species number, the HFD and AIN diets
      resulted in different bacterial community structures in the colon. The abundance
      of certain short-chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella)
      and fecal SCFA (e.g., acetic acid) content were lower in the HFD-AOM group
      compared with the AIN and AIN-AOM groups. Furthermore, we identified a high
      abundance of Anaeroplasma bacteria, an opportunistic pathogen in the HFD-AOM
      group. Collectively, we demonstrate that an HFD promotes AC formation concurrent
      with an increase of opportunistic pathogenic bacteria in the colon of C57BL/6
      mice.

PMID- 29223828
TI  - Rationale for combination of therapeutic antibodies targeting tumor cells and
      immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1
      isotype immune effector stimulation.
AB  - Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated
      cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a
      standard-of-care treatment for locally advanced and recurrent and/or metastatic
      squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal
      cancer (CRC). Here we review evidence regarding the clinical relevance of
      cetuximab-mediated ADCC and other immune functions and provide a biological
      rationale concerning why this property positions cetuximab as an ideal partner
      for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We
      performed a nonsystematic review of available preclinical and clinical data
      involving cetuximab-mediated immune activity and combination approaches of
      cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed,
      cetuximab mediates ADCC activity in the intratumoral space and primes adaptive
      and innate cellular immunity. However, counterregulatory mechanisms may lead to
      immunosuppressive feedback loops. Accordingly, there is a strong rationale for
      combining ICIs with cetuximab for the treatment of advanced tumors, as targeting
      CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter
      mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other
      immunotherapies) with cetuximab is a promising strategy for boosting immune
      response and enhancing response rates and durability of response. Cetuximab
      immune activity-including, but not limited to, ADCC-provides a strong rationale
      for its combination with ICIs or other immunotherapies to synergistically and
      fully mobilize the adaptive and innate immunity against tumor cells. Ongoing
      prospective studies will evaluate the clinical effect of these combination
      regimens and their immune effect in CRC and SCCHN and in other indications.

PMID- 29223829
TI  - Is Depression with increased antithyroid autoantibodies a mere chance finding or
      Hashimoto's Encephalopathy?

PMID- 29223830
TI  - Being 80% female and 20% male: Delusional pseudotransexualism in a case of
      Schizophrenia.

PMID- 29223831
TI  - Braid cut anxiety in females: A newly emerged epidemic of mass hysteria in North
      India.

PMID- 29223832
TI  - Surgery for mesothelioma: Less is more, more or less.

PMID- 29223833
TI  - Valve-sparing repair with intraoperative balloon dilation in tetralogy of Fallot:
      Midterm results and therapeutic implications.
AB  - OBJECTIVES: The significant morbidity of long-term pulmonary regurgitation (PR)
      has driven the development of pulmonary valve (PV) sparing repair strategies in
      patients with tetralogy of Fallot (ToF). We assessed mid-term PV function in
      patients who underwent primary ToF repair with valve-sparing intraoperative
      balloon dilation (IBD) technique. METHODS: We evaluated 162 consecutive patients
      with ToF and pulmonary stenosis (ToF-PS) who underwent valve-sparing repair with
      IBD under 1 year of age. RESULTS: Median age at surgery was 98 days
      (interquartile range [IQR], 72-126) and median follow-up was 2.5 years (IQR, 0.6
      4.9). Median preoperative PV annulus z score was -2.2 (IQR, -2.5 to -1.8). Twenty
      five patients (15.4%) required reintervention for residual valvular stenosis.
      Multivariable analysis demonstrated preoperative annulus z score less than -2.45
      (P = .036) and younger age at surgery (P = .001) were independent risk factors
      for early reintervention for stenosis. Freedom from at least moderate PR was 77%,
      61%, and 43% at 1, 3, and 5 years postrepair. Right ventricular dimensions were
      not significantly different compared with a matched cohort of patients undergoing
      transannular patch repair at midterm follow-up. CONCLUSIONS: Patients with ToF-PS
      who undergo valve-sparing repair with IBD develop progressive PR. Compared with
      transannular patch repair, the extent of RV dilation at midterm follow-up is not
      significantly different. Patients younger than 3 months of age and those with an
      annulus z score less than -2.45 experience higher rates of early reintervention
      for PV stenosis. In these patient subgroups, alternative strategies should be
      considered. This study suggests valve-sparing repair with IBD does not preserve
      long-term PV function in patients with ToF-PS.

PMID- 29223834
TI  - Prognostic significance and adjuvant chemotherapy survival benefits of a solid or
      micropapillary pattern in patients with resected stage IB lung adenocarcinoma.
AB  - OBJECTIVE: To evaluate the prognostic significance and beneficiaries of adjuvant
      chemotherapy (ACT) in various histological patterns of stage IB lung
      adenocarcinoma according to the 8th tumor-node-metastasis (TNM) classification.
      METHODS: A total of 1131 patients with pathological stage IB lung adenocarcinoma
      according to the 8th TNM classification who underwent lobectomy or segmentectomy
      were enrolled in this study. Based on the proportion of solid/micropapillary
      components, the patients were classified into 3 groups: solid/micropapillary
      negative (SMPN) (n = 719; median survival, 49.7 months; interquartile range
      [IQR]. 35.1-67.0 months), solid/micropapillary-minor (SMPM; >5% but not
      predominant) (n = 272; median survival, 38.8 months; IQR, 26.6-51.5 months) and
      solid/micropapillary-predominant (SMPP; >5% and the most dominant) (n = 140;
      median survival, 39.6 months; IQR, 26.8-52.5 months). The predictors of disease
      specific survival and recurrence-free survival were investigated. To reduce
      selection bias, propensity score-matching analysis was implemented before
      survival data were compared. RESULTS: Our data show significant differences in
      survival rates based on the proportion of solid/micropapillary patterns. The SMPM
      group had significantly higher cumulative incidences of lung cancer-specific
      death (P = .000) and recurrence (P = .000) compared with the SMPN group, so did
      the SMPP group when compared with SMPM patients (P = .000 for both). Multivariate
      analysis showed that the SMPM and SMPP patterns were poor prognostic factors for
      disease-specific survival (hazard ratio [HR], 1.86; 95% confidence interval [CI],
      1.12-3.09 and HR, 4.56; 95% CI, 2.69-7.71, respectively) and recurrence-free
      survival (HR, 1.64; 95% CI, 1.20-2.24 and HR, 2.43; 95% CI, 1.64-3.60,
      respectively), as were older age, male sex, smoking history, larger tumor size,
      necrosis, and abnormal pulmonary function. Survival analysis stratified by
      histological pattern showed that patients with the SMPP pattern who received ACT
      had obviously lower cumulative incidences of lung cancer-specific death (HR,
      0.46; 95% CI, 0.22-0.93; P = .031) and recurrence (HR, 0.48; 95% CI, 0.26-0.88; P
      = .017). CONCLUSIONS: Solid/micropapillary patterns were associated with poor
      prognosis, even if they were not predominant. ACT contributed to survival
      benefits in the SMPP subgroup of patients with stage IB lung adenocarcinoma.

PMID- 29223835
TI  - Discussion.

PMID- 29223836
TI  - Everybody is different: A plea for individualizing treatment of aortopathy.

PMID- 29223837
TI  - Quadricuspid aortic valve surgical repair.

PMID- 29223838
TI  - Time to celebrate!

PMID- 29223839
TI  - Sequential segmentectomy: Known knowns, known unknowns, and unknown unknowns.

PMID- 29223840
TI  - All the small things: The impact of central venous catheters in neonates
      undergoing cardiac surgery.

PMID- 29223841
TI  - Adjuvant chemotherapy for resected earlier stage adenocarcinomas with unfavorable
      architecture. Should we incorporate histologic findings to the decision tree?

PMID- 29223842
TI  - Interstage evaluation of homograft-valved right ventricle to pulmonary artery
      conduits for palliation of hypoplastic left heart syndrome.
AB  - OBJECTIVE: Palliation of hypoplastic left heart syndrome with a standard
      nonvalved right ventricle to pulmonary artery conduit results in an inefficient
      circulation in part due to diastolic regurgitation. A composite right ventricle
      pulmonary artery conduit with a homograft valve has a hypothetical advantage of
      reducing regurgitation, but may differ in the propensity for stenosis because of
      valve remodeling. METHODS: This retrospective cohort study included 130 patients
      with hypoplastic left heart syndrome who underwent a modified stage 1 procedure
      with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite
      valved conduit (cryopreserved homograft valve anastomosed to a
      polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32
      pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was
      used in 30 patients. Echocardiographic functional parameters were evaluated
      before and after stage 1 palliation and before the bidirectional Glenn procedure,
      and interstage interventions were assessed. RESULTS: On competing risk analysis,
      survival over time was better in the valved conduit group (P = .040), but this
      difference was no longer significant after adjustment for surgical era. There was
      no significant difference between groups in the cumulative incidence of
      bidirectional Glenn completion (P = .15). Patients with a valved conduit
      underwent more interventions for conduit obstruction in the interstage period,
      but this difference did not reach significance (P = .16). There were no
      differences between groups in echocardiographic parameters of right ventricle
      function at baseline or pre-Glenn. CONCLUSIONS: In this cohort of patients with
      hypoplastic left heart syndrome, inclusion of a valved right ventricle to
      pulmonary artery conduit was not associated with any difference in survival on
      adjusted analysis and did not confer an identifiable benefit on right ventricle
      function.

PMID- 29223843
TI  - Robotic surgery: Maximizing the potential of a minimally invasive platform.

PMID- 29223844
TI  - Bicuspid aortopathy: Seeing the forest for the trees.

PMID- 29223845
TI  - Seeing is believing: A call for routine early postoperative hemodynamic
      transesophageal echocardiography monitoring after left ventricular assist device
      implantation?

PMID- 29223846
TI  - Clinical features and surgical outcomes of pulmonary artery sarcoma.
AB  - OBJECTIVE: Pulmonary artery sarcoma is an exceedingly rare malignancy. There is a
      lack of consensus regarding its diagnosis and treatment. We reviewed our
      experience in the surgical management of pulmonary artery sarcoma over an 11-year
      period. METHODS: From January 2005 to February 2016, 12 patients with pulmonary
      artery sarcoma (age 51 +/- 14 years, 5 male) underwent surgical treatment at our
      center. Nine patients (75%) exhibited pulmonary trunk involvement on computed
      tomography angiography. Six patients (50%) were initially misdiagnosed with
      pulmonary embolism. RESULTS: Ten patients underwent pulmonary endarterectomy, and
      3 of these patients required additional unilateral pneumonectomy. The remaining 2
      patients underwent exploratory thoracotomy. One patient (8.3%) died in the
      hospital. The median length of postoperative intensive care unit and hospital
      stay were 1 day (range, 1-15 days) and 8 days (range, 5-21 days), respectively.
      The median postoperative survival of the total series was 18 months. Patients who
      received postoperative combined chemo- and radiotherapy were associated with
      improved survival compared with those who had isolated adjuvant therapy or
      surgery alone (median survival 28 vs 8 months, P = .042). CONCLUSIONS: Although
      pulmonary artery sarcoma has a very poor prognosis, surgical treatment offers a
      chance for symptom relief and better long-term outcome. Aggressive postoperative
      adjuvant treatment may be necessary to improve survival.

PMID- 29223847
TI  - Funding breakthrough therapies: A systematic review and recommendation.
AB  - BACKGROUND: Advanced therapy medicinal products (ATMPs) are innovative therapies
      likely associated with high prices. Payers need guidance to create a balance
      between ensuring patient access to breakthrough therapies and maintaining the
      financial sustainability of the healthcare system. OBJECTIVE: The aims of this
      study were to identify, define, classify and compare the approaches to funding
      high-cost medicines proposed in the literature, to analyze their appropriateness
      for ATMP funding and to suggest an optimal funding model for ATMPs. RESULTS:
      Forty-eight articles suggesting new funding models for innovative high-cost
      therapies were identified. The models were classified into 3 groups: financial
      agreement, health outcomes-based agreement and healthcoin. Financial agreement
      encompassed: discounts, rebates, price and volume caps, price-volume agreements,
      loans, cost-plus price, intellectual-based payment and fund-based payment. Health
      outcomes-based agreements were defined as agreements between manufacturers and
      payers based on drug performance, and were divided into performance-based payment
      and coverage with evidence development. Healthcoin described a new suggested
      tradeable currency used to assign monetary value to incremental outcomes.
      CONCLUSION: With a large number of ATMPs in development, it is time for
      stakeholders to start thinking about new pathways and funding strategies for
      these innovative high-cost therapies. An "ATMP-specific fund" may constitute a
      reasonable solution to ensure rapid patient access to innovation without
      threatening the sustainability of the health care system.

PMID- 29223848
TI  - Foliar spraying of salicylic acid induced accumulation of phenolics, increased
      radical scavenging activity and modified the composition of the essential oil of
      water stressed Thymus vulgaris L.
AB  - Polyphenolic compounds are considered valuable secondary plant metabolites owing
      to the myriad of biological activities they exert. This study aimed to
      investigate the effect of applying various concentrations of the plant growth
      regulator, salicylic acid (SA), on Thymus vulgaris L. while subjecting the plant
      to decreasing amounts of irrigation water. The following parameters were
      monitored; total polyphenolic and flavonoid content, yield and composition of the
      essential oil, and antioxidant activity of the alcoholic extracts. Drought alone
      significantly (P < 0.05) increased the polyphenolic and flavonoid content, yield
      of the essential oil and antioxidant activity. The total flavonoid content in
      control plants was 6.1 +/- 0.3 mg/gm dry weight calculated in terms of rutin
      equivalent. However, in drought stressed plants, (irrigated at 25% of the field
      capacity) sprayed with 3 mM SA, the flavonoid content increased to 32.1 +/- 0.1
      mg/gm dry weight calculated in terms of rutin equivalent. Moreover, the total
      phenolic content increased from 8.5 +/- 0.3 to 68.5 +/- 1.2 mg/gm dry weight
      calculated in terms of gallic acid in the same test plants. Radical scavenging
      activity, using DPPH assay, was measured for the different plant treatments. A
      decrease from 74.4 +/- 0.4 MUg/ml to 36.6 +/- 0.9 MUg/ml of IC50 was recorded in
      the drought stressed plants (25% FC) sprayed with 3 mM SA compared with the
      control plants. The variability in polyphenolic composition between the control
      plants and plants with the highest total polyphenolic content was investigated by
      UPLC-ESI-MS/MS. Rosmarinic acid was detected as the major component in samples
      from both treatments, with a higher percentage observed upon subjecting the plant
      to the test conditions (25% FC and sprayed with 3 mM SA). The highest yield of
      the essential oil (1 +/- 0.06 %v/w) was obtained from drought stressed plants
      (25% FC) sprayed with 2 mM SA. GC/MS analysis of oil samples revealed that the
      Thymol content increased with drought stress, while that of p-cymene decreased.
      However, an increase of p-cymene was witnessed as a result of SA spraying.

PMID- 29223849
TI  - Subcellular distribution of molybdenum, ultrastructural and antioxidative
      responses in soybean seedlings under excess molybdenum stress.
AB  - Some studies have shown that excess molybdenum (Mo) could produce toxic effects
      on plants. However, little is known about the subcellular distribution of Mo and
      cell ultrastructure within plants under excess Mo stress. Here, we
      comprehensively analyzed the changes of Mo distribution in subcellular fractions,
      cell ultrastructure and antioxidant enzymes in leaves and roots of soybean
      seedlings in response to excess Mo stress. The results showed that roots
      exhibited higher Mo accumulation than leaves at the 100 mg L-1 Mo level, about
      38.58-, 171.48- and 52.99-fold higher in cell walls, cell organelles and soluble
      fractions, respectively. Subcellular fractionations of Mo-containing tissues
      indicated that approximately 90% of Mo was accumulated in the soluble fractions
      and cell walls of the roots and leaves, and soluble fractions (accumulated 66.3
      72.2% Mo) might serve as an effective storage site for excess Mo. Furthermore,
      excess Mo caused ultrastructural alterations in roots and leaves of soybean
      seedlings, leading to structural abnormality of chloroplast in leaf cells,
      plasmolysis, cellular deformity, vacuole enlargement and the swelling of cell
      wall and cytoplasm in root cells. Meanwhile, under excess Mo stress, the activity
      of POD, CAT and APX enzymes in roots was 1.43, 2.35 and 1.23 times that under
      standard Mo condition, while that of SOD and CAT enzymes in leaves was 1.23 and
      1.94 times, respectively. This study provided novel insights into the mechanisms
      of excess Mo toxicity in soybean seedlings.

PMID- 29223850
TI  - Genome-wide analysis of carotenoid cleavage oxygenase genes and their responses
      to various phytohormones and abiotic stresses in apple (Malus domestica).
AB  - Carotenoid cleavage oxygenases (CCOs) are able to cleave carotenoids to produce
      apocarotenoids and their derivatives, which are important for plant growth and
      development. In this study, 21 apple CCO genes were identified and divided into
      six groups based on their phylogenetic relationships. We further characterized
      the apple CCO genes in terms of chromosomal distribution, structure and the
      presence of cis-elements in the promoter. We also predicted the cellular
      localization of the encoded proteins. An analysis of the synteny within the apple
      genome revealed that tandem, segmental, and whole-genome duplication events
      likely contributed to the expansion of the apple carotenoid oxygenase gene
      family. An additional integrated synteny analysis identified orthologous
      carotenoid oxygenase genes between apple and Arabidopsis thaliana, which served
      as references for the functional analysis of the apple CCO genes. The net
      photosynthetic rate, transpiration rate, and stomatal conductance of leaves
      decreased, while leaf stomatal density increased under drought and saline
      conditions. Tissue-specific gene expression analyses revealed diverse
      spatiotemporal expression patterns. Finally, hormone and abiotic stress
      treatments indicated that many apple CCO genes are responsive to various
      phytohormones as well as drought and salinity stresses. The genome-wide
      identification of apple CCO genes and the analyses of their expression patterns
      described herein may provide a solid foundation for future studies examining the
      regulation and functions of this gene family.

PMID- 29223851
TI  - Additional value of anaerobic threshold in a general mortality prediction model
      in a urban patient cohort with Chagas cardiomyopathy.
AB  - BACKGROUND: Anaerobic threshold (AT) is recognized as objective and direct
      measurement that reflects variations in metabolism of skeletal muscles during
      exercise. Its prognostic value in heart diseases of non-chagasic etiology is well
      established. However, the assessment of risk of death in Chagas heart disease is
      relatively well established by Rassi score. But, the added value that AT can
      bring to Rassi score has not been studied yet. OBJECTIVES: To assess whether AT
      presents additional effect to Rassi score in patients with chronic Chagas' heart
      disease. METHODS: Prospective research of dynamic cohort by review of 150 medical
      records of patients. Were selected for cohort 45 medical records of patients who
      underwent cardiopulmonary exercise testing between 1996-1997 and followed until
      September 2015. Data analysis to detect association between studied variables can
      be seen using a logistic regression model. The suitability of the models was
      verified using ROC curves and the coefficient of determination R2. RESULTS: 8
      patients (17.78%) died by September 2015, with 7 of them (87.5%) from
      cardiovascular causes, of which 4 (57.14%) were considered on high risk by Rassi
      score. With Rassi score as independent variable, and death being the outcome, we
      obtained an area under the curve (AUC)=0.711, with R2=0.214. Instituting AT as
      independent variable, we found AUC=0.706, with R2=0.078. When we define Rassi
      score and AT as independent variables, it was obtained AUC=0.800 and R2=0.263.
      CONCLUSION: when AT is included in logistic regression, it increases by 5% the
      explanation (R2) to the death estimation.

PMID- 29223852
TI  - More effective prediction of mortality in Chagas heart disease patients?
      Importance of cardiopulmonary stress testing.

PMID- 29223853
TI  - Role of miR-195 in cigarette smoke-induced chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is regarded as a persistent
      respiratory symptom, mainly caused by cigarette smoking. Recent data have
      suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we
      found that miR-195 was significantly upregulated in the lung tissues of patients
      with COPD compared to in never smokers. miR-195 expression was also upregulated
      in cigarette smoke (CS)-exposed mice. Lentivirus-mediated knockdown of miR-195
      alleviated CS-induced lung pathological changes and reduced inflammatory cell
      infiltration as well as production of interleukin-6 and tumor necrosis factor
      alpha in bronchoalveolar lavage fluid. Mechanically, a positive correlation was
      found between miR-195 and phosphorylation of Akt in lung tissues of COPD
      patients. PHLPP2 was confirmed as a direct downstream target of miR-195 and
      negative regulator of miR-195 expression. Inhibition of PHLPP2 enhanced Akt
      phosphorylation and increased interleukin-6 and tumor necrosis factor-alpha
      production in BEAS-2B cells, resembling the effects of miR-195 overexpression.
      Collectively, our data indicate that miR-195 has a pathogenetic role in CS
      induced COPD and regulates Akt signaling by suppressing PHLPP2 expression. miR
      195 may be an effective therapeutic target in COPD.

PMID- 29223854
TI  - Baicalein improves liver inflammation in diabetic db/db mice by regulating
      HMGB1/TLR4/NF-kappaB signaling pathway.
AB  - The current study was designed to investigate the hepatoprotective effects and
      possible mechanisms of Baicalein (BA) on the diabetic liver injury in vivo and in
      vitro. The results exhibited that BA significantly restored the blood glucose in
      oral glucose tolerance test (OGTT) and inhibited the levels of insulin, alanine
      aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC)
      and triglyceride (TG) in C57BL/KsJ-db/db mice. Moreover, BA strikingly attenuated
      the extent of steatosis in the liver tissues of diabetic mice. These results
      confirmed the hepatoprotective effects of BA on diabetic liver injury. Further in
      vivo investigations revealed that the hepatoprotective activities of BA was due
      to the effects on remarkably suppressing the inflammatory cascade, including
      attenuating the expressions of HMGB1, TLR4, Myd88, NF-kappaB and IkappaB proteins
      and inhibiting the production of interleukin (IL)-1beta, IL-6 and tumor necrosis
      factor (TNF)-alpha in diabetic mice. Finally, the hepatoprotective effects of BA
      were characterized in human hepatic HepG2 cells. With response to palmitic acid
      challenge, increased amount of insulin, ALT, AST, TG, TC were observed, whereas
      BA pretreatment significantly restored these changes in HepG2 cells. Inflammation
      condition was also recovered with BA treatment as shown by the changes of HMGB1,
      TLR4, Myd88, NF-kappaB and IkappaB expressions and the levels of IL-1beta, IL-6
      and TNF-alpha. These findings elucidated that BA exhibited prominent
      hepatoprotective activities in diabetic live injury.

PMID- 29223855
TI  - Increased ADAM10 expression in patients with immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease, which is characterized by
      abnormal of T immunity. A disintegrin and metalloproteinase (ADAM) 10, a member
      of proteinase family, has been demonstrated to regulate T cell proliferation and
      effector function. Considering the closely association of dysregulation of T cell
      function with ITP, whether ADAM10 involves in the pathogenesis of ITP remains
      unclear. In this study, 54 active ITP patients, 18 ITP in remission and 24 age
      and gender matched healthy control were enrolled. Peripheral blood mononuclear
      cells (PBMCs) were isolated from patients and control for isolation of RNA and
      plasma which were used to measure mRNA level of ADAM10 and tissue inhibitor of
      metalloproteinase 3 (TIMP3) by quantitative real-time PCR and soluble level of
      FasL and lymphocyte activation gene-3 (LAG-3) in plasma by ELISA. Meanwhile, T
      cell activation was measured by flow cytometry. Our results showed significantly
      higher expression of ADAM10 and lower expression of TIMP3 in active ITP patients
      compared with control, which were all restored into normal level in remission
      patients. Consistent with the expression profile of ADAM10, increased soluble
      plasma level of FasL and LAG-3 were observed in active ITP patients and reduced
      to normal level in patients in remission. Furthermore, increased T cell
      activation as demonstrated by higher expression of HLA-DR and CD69 were found in
      active ITP patients. In conclusion, elevated expression of ADAM10 was associated
      with the pathogenesis and development of ITP and therapeutically targeting it
      might be a novel approach for the treatment of ITP.

PMID- 29223856
TI  - Modulation of glutathione peroxidase activity by age-dependent carbonylation in
      glomeruli of diabetic mice.
AB  - AIMS: Low levels of reactive oxygen species and resulting oxidative protein
      modifications may play a beneficial role in cellular function under stress
      conditions. Here we studied the influence of age-dependent protein carbonylation
      on expression and activity of the anti-oxidative selenoenzyme glutathione
      peroxidase (GPx) in insulin-deficient Ins2Akita mice and type 2 diabetic obese
      db/db mice in context of diabetic nephropathy. METHODS: Protein carbonylation,
      GPx expression and activity were examined in kidney tissue and lysates by common
      histological and protein biochemical methods. RESULTS: In kidneys of Ins2Akita
      mice, carbonylated proteins, GPx-1 and GPx-4 expression were mainly detected in
      podocytes and mesangial cells. GPx activity was increased in kidney cortex
      homogenates of these mice. Remarkably, young animals did not show a concomitant
      increase in GPx expression but enhanced GPx carbonylation. No carbonylation
      dependent modification of GPx activity was detected in db/db mice. In cultured
      podocytes hyperglycemia induced an increase in GPx expression but had no effect
      on activity or carbonylation. In kidney tissue sections of type 1 or type 2
      diabetes patients, GPx-1 and GPx-4 expression but not overall protein
      carbonylation was significantly decreased. CONCLUSIONS: These results indicate
      the existence of a threshold for beneficial carbonylation-dependent redox
      signaling during the progression of diabetic nephropathy.

PMID- 29223857
TI  - When it is apt to adapt: Flexible reasoning guides children's use of talker
      identity and disfluency cues.
AB  - An eye-tracking methodology was used to examine whether children flexibly engage
      two voice-based cues, talker identity and disfluency, during language processing.
      Across two experiments, 5-year-olds (N = 58) were introduced to two characters
      with distinct color preferences. These characters then used fluent or disfluent
      instructions to refer to an object in a display containing items bearing either
      talker-preferred or talker-dispreferred colors. As the utterance began to unfold,
      the 5-year-olds anticipated that talkers would refer to talker-preferred objects.
      When children then encountered a disfluency in the unfolding description, they
      reduced their expectation that a talker was about to refer to a preferred object.
      The talker preference-related predictions, but not the disfluency-related
      predictions, were attenuated during the second half of the experiment as evidence
      accrued that talkers referred to dispreferred objects with equal frequency. In
      Experiment 2, the equivocal nature of talkers' referencing was made more apparent
      by removing neutral filler trials, where objects' colors were not associated with
      talker preferences. In this case, children ceased making all talker-related
      predictions during the latter half of the experiment. Taken together, the results
      provide insights into children's use of talker-specific cues and demonstrate that
      flexible and adaptive forms of reasoning account for the ways in which children
      draw on paralinguistic information during real-time processing.

PMID- 29223858
TI  - How to review an abstract for a scientific meeting.

PMID- 29223859
TI  - Outcome of pediatric renal transplantation in urological versus non-urological
      causes of end stage renal disease: Does it matter?
AB  - INTRODUCTION: Causes for end stage renal disease (ESRD) in children can be
      categorized into urological causes or non-urological causes. We sought to compare
      the outcomes of urological and non-urological causes of ESRD in children.
      METHODS: Patients were divided into two groups: urological causes of ESRD versus
      non-urological causes of ESRD. All patients and donors had at least 6 months of
      follow-up. The main outcomes included the effect on complications and renal
      function. Comparisons were carried out using the chi-square test or the Student t
      test. Multivariate logistic regression analysis was used to define the effect of
      different variables on the outcome of renal transplantation (Table). RESULTS: Our
      study included 123 patients, 91 males. The mean age was 9 years and mean follow
      up was 46 months. Two-thirds of the patients had non-urological causes of ESRD.
      Overall survival was 100%, and only one patient needed a graft nephrectomy 3
      months after the transplant. The mean estimated glomerular filtration rate was
      117 mL/min, and did not differ significantly between the two groups (p = 0.13).
      Multivariable regression showed that female gender (OR 8.7, 95% CI 2.9-26, p = 0
      0.0001) was associated with better renal function, while having a urological
      cause of ESRD (OR 0.28, CI 0.08-0.98, p = 0 0.05) was associated with worse renal
      function. Non-urological causes of ESRD were significantly less likely to develop
      complications following renal transplantation (OR 0.28, CI 0.09-0.89, p = 0
      0.03). CONCLUSION: Female patients with non-urological causes of ESRD are more
      likely to have better long-term renal functions, and less liable to develop
      complications following renal transplant.

PMID- 29223860
TI  - Time resolution requirements for civilian radioxenon emission data for the CTBT
      verification regime.
AB  - The capability of the noble gas component of the International Monitoring System
      as a verification tool for the Comprehensive Nuclear-Test-Ban Treaty is
      deteriorated by a background of radioxenon emitted by civilian sources. One of
      the possible approaches to deal with this issue, is to simulate the daily
      radioxenon concentrations from these civilian sources at noble gas stations by
      using atmospheric transport models. In order to accurately quantify the
      contribution from these civilian sources, knowledge on the releases is required.
      However, such data are often not available and furthermore it is not clear what
      temporal resolution such data should have. In this paper, we assess which
      temporal resolution is required to best model the 133Xe contribution from
      civilian sources at noble gas stations in an operational context. We consider
      different sampling times of the noble gas stations and discriminate between
      nearby and distant sources. We find that for atmospheric transport and dispersion
      problems on a scale of 1000 km or more, emission data with subdaily temporal
      resolution is generally not necessary. However, when the source-receptor distance
      decreases, time-resolved emission data become more important. The required
      temporal resolution of emission data thus depends on the transport scale of the
      problem. In the context of the Comprehensive Nuclear-Test-Ban Treaty, where forty
      noble gas stations will monitor the whole globe, daily emission data are
      generally sufficient, but for certain meteorological conditions, better
      temporally resolved emission data are required.

PMID- 29223861
TI  - How lack of physiotherapist out-of-hours led to nurses developing their role: A
      UK case study.
AB  - The aim of this article is to share the experience of how a multi-disciplinary
      team worked together to develop the nursing role to incorporate the practitioners
      supporting mobilisation of a patient. The role developed nurses' competence,
      ensuring that the information and instruction patients received were consistent
      between therapists and nursing staff, but also supported the Enhanced Recovery
      Programme (2010). There were issues with the level of therapy support, especially
      out of hours. The team agreed a vision together, with a solution to the problem
      on how the mobilisation of patients post-surgery could be achieved. This would
      ensure postoperative complications were reduced and that there was continuity in
      education for the patients. This experience is an example of how staff can be
      empowered to provide patients with a positive experience through challenging
      practices and behaviours and resulting in innovative practice and role
      development.

PMID- 29223863
TI  - What can predict and prevent the long-term use of benzodiazepines?
AB  - Although benzodiazepines (BZDs) are commonly prescribed for insomnia or anxiety,
      long-term use of BZDs causes serious adverse effects such as daytime drowsiness
      and cognitive decline. In the current study, we evaluated the predictors and
      preventers of long-term usage of BZDs from a retrospective survey by utilizing
      the 12-year prescription record of a university hospital. From the prescription
      data of 92,005 people, users of BZDs (n = 3,470, male = 39.2%, mean age = 60 +/-
      17.5) were analyzed. During this period, both the number of prescriptions (2722
      in 2004 to 1019 in 2016) and the number of BZDs (1.73 in 2004 to 1.36 in 2016)
      gradually decreased, although more than half of the patients continued to take
      BZDs for over three years. High risk factors for long-term use of BZDs include
      elderly patients (>65 years old), high dosage (>5 mg diazepam per day),
      psychiatrist-prescribers, and users with polytherapy. Discontinuation is
      significantly found in users of hypnotic BZDs and alternative psychotropic
      medical drugs (including antipsychotics, serotonergic drugs, or newer types of
      sleep medicine). Future studies should focus on elucidating interventions that
      are more effective against long-term usage of BZDs.

PMID- 29223864
TI  - Involuntary top-down control by search-irrelevant features: Visual working memory
      biases attention in an object-based manner.
AB  - Many everyday tasks involve successive visual-search episodes with changing
      targets. Converging evidence suggests that these targets are retained in visual
      working memory (VWM) and bias attention from there. It is unknown whether all or
      only search-relevant features of a VWM template bias attention during search.
      Bias signals might be configured exclusively to task-relevant features so that
      only search-relevant features bias attention. Alternatively, VWM might maintain
      objects in the form of bound features. Then, all template features will bias
      attention in an object-based manner, so that biasing effects are ranked by
      feature relevance. Here, we investigated whether search-irrelevant VWM template
      features bias attention. Participants had to saccade to a target opposite a
      distractor. A colored cue depicted the target prior to each search trial. The
      target was predefined only by its identity, while its color was irrelevant. When
      target and cue matched not only in identity (search-relevant) but also in color
      (search-irrelevant), saccades went more often and faster directly to the target
      than without any color match (Experiment 1). When introducing a cue-distractor
      color match (Experiment 2), direct target saccades were most likely when target
      and cue matched in the search-irrelevant color and least likely in case of a cue
      distractor color match. When cue and target were never colored the same
      (Experiment 3), cue-colored distractors still captured the eyes more often than
      different-colored distractors despite color being search-irrelevant. As
      participants were informed about the misleading color, the result argues against
      a strategical and voluntary usage of color. Instead, search-irrelevant features
      biased attention obligatorily arguing for involuntary top-down control by object
      based VWM templates.

PMID- 29223862
TI  - WAVE regulates Cadherin junction assembly and turnover during epithelial
      polarization.
AB  - Actin is an integral component of epithelial apical junctions, yet the
      interactions of branched actin regulators with apical junction components are
      still not clear. Biochemical data have shown that alpha-catenin inhibits Arp2/3
      dependent branched actin. These results suggested that branched actin is only
      needed at earliest stages of apical junction development. We use live imaging in
      developing C. elegans embryos to test models for how WAVE-induced branched actin
      collaborates with other apical junction proteins during the essential process of
      junction formation and maturation. We uncover both early and late essential roles
      for WAVE in apical junction formation. Early, as the C. elegans intestinal
      epithelium becomes polarized, we find that WAVE components become enriched
      concurrently with the Cadherin components and before the DLG-1 apical
      accumulation. Live imaging of F-actin accumulation in polarizing intestine
      supports that the Cadherin complex components and branched actin regulators work
      together for apical actin enrichment. Later in junction development, the apical
      accumulation of WAVE and Cadherin components is shown to be interdependent:
      Cadherin complex loss alters WAVE accumulation, and WAVE complex loss increases
      Cadherin accumulation. To determine why Cadherin levels rise when WVE-1 is
      depleted, we use FRAP to analyze Cadherin dynamics and find that loss of WAVE as
      well as of the trafficking protein EHD-1/RME-1 increases Cadherin dynamics. EM
      studies in adults depleted of branched actin regulators support that WVE-1
      maintains established junctions, presumably through its trafficking effect on
      Cadherin. Thus we propose a developmental model for junction formation where
      branched actin regulators are tightly interconnected with Cadherin junctions
      through their previously unappreciated role in Cadherin transport.

PMID- 29223865
TI  - Prevention of ischemia-induced hearing loss by intravenous administration of
      hydrogen-rich saline in gerbil.
AB  - OBJECTIVE: Hydrogen-rich water, which is a potent antioxidant agent, was
      investigated for its protective effects against ischemic damage of the cochlea in
      gerbils. METHODS: The animals were subjected to transient cochlear ischemia by
      occluding the bilateral vertebral arteries for l5min. Five milliliters of
      hydrogen-rich saline was then intravenously administered immediately after the
      insult. Saline without hydrogen was used as a control. Effects of hydrogen were
      evaluated using the auditory brainstem response (ABR) and histological studies of
      the inner ear. RESULTS: In non-ischemia animals, ABR thresholds and histological
      findings of the cochlea did not change by administration of saline or hydrogen
      rich saline. In contrast, transient cochlear ischemia caused a 24.2+/-3.8dB
      increase in the ABR threshold at 8kHz, and a decrease of 14.1%+/-1.8% in the
      number of inner hair cells (IHCs) at the basal turn on day 7. Ischemic damage was
      more severe at 16 and 32kHz. When the animals were treated with hydrogen-rich
      saline, cochlear damage was significantly reduced: the increase in ABR threshold
      was 11.7+/-2.6dB at 8kHz and the IHC loss was 7.5%+/-2.1% at the basal turn on
      day 7. The effects of hydrogen-rich saline were more prominent at higher
      frequencies. CONCLUSIONS: Intravenous administration of hydrogen-rich saline was
      effective in preventing acute hearing loss due to transient cochlear ischemia.

PMID- 29223866
TI  - Phase delays between tone pairs reveal interactions in scalp-recorded envelope
      following responses.
AB  - Evoked potentials to envelope periodicity in sounds, such as vowels, are
      dependent on the stimulus spectrum. We hypothesize that phase differences between
      responses elicited by multiple frequencies spread tonotopically across the
      cochlear partition may contribute to variation in scalp-recorded amplitude. The
      present study evaluated this hypothesis by measuring envelope following responses
      (EFRs) to two concurrent tone pairs, p1 and p2, that approximated the first and
      second formant frequencies of a vowel, while controlling their relative envelope
      phase. We found that the scalp-recorded amplitude of EFRs changed significantly
      in phase and amplitude when the envelope phase of p2, the higher frequency tone
      pair, was delayed. The maximum EFR amplitude occurred at the p2 envelope phase
      delay of 90 degrees , likely because the stimulus delay compensated for the
      average phase lead of 73.57 degrees  exhibited by p2-contributed EFRs relative to
      p1-contributed EFRs, owing to earlier cochlear processing of higher frequencies.
      Findings suggest a linear superimposition of independently generated EFRs from
      tonotopically separated pathways. This suggests that introducing frequency
      specific delays may help to optimize EFRs to broadband stimuli like vowels.

PMID- 29223867
TI  - The comprehensive analysis of sorghum cultivated in Poland for energy purposes:
      Separate hydrolysis and fermentation and simultaneous saccharification and
      fermentation methods and their impact on bioethanol effectiveness and volatile by
      products from the grain and the energy potential of sorghum straw.
AB  - The aim of this work was to study the potential of sorghum crop cultivated in
      European climate as an energy material. The investigation showed strong
      interaction between the fermentation method and the sorghum cultivar. It was also
      noted that the cultivar with the highest grain yield showed the highest yield of
      ethanol per hectare, achieving 1269 L/ha in SHF (separate hydrolysis and
      fermentation) and 1248 L/ha in SSF (simultaneous saccharification and
      fermentation). Chromatographic analysis of raw spirits showed that smaller
      amounts of impurities are formed in the SSF process than in the SHF process. The
      calorific value of sorghum straw was also measured, and amounted to 16,050-16,840
      kJ/kg. The results have demonstrated the high value of sorghum as grain for
      bioethanol production and as straw as a valuable feedstock for forming pellets or
      briquettes.

PMID- 29223868
TI  - Recirculation of gas emissions to achieve advanced denitrification of the
      effluent from the anaerobic treatment of domestic wastewater.
AB  - A denitrifying pilot plant was designed, constructed and operated for more than
      five months. The plant treated domestic wastewater with high ammonium nitrogen
      concentration, which had previously undergone an anaerobic process at 18  degrees
      C. The process consisted of one biofilter with 2 h of hydraulic retention time
      for denitritation. Different synthetic nitrite concentrations were supplied to
      the anoxic reactor to simulate the effluent of a nitritation process. This work
      investigates the advanced denitritation of wastewater using the organic matter
      and other alternative electron donors present in an anaerobic treatment process
      effluent: methane and sulfide. The denitrifying bacteria were able to treat
      wastewater at an inlet nitrite concentration of 75 mg NO2--N/L with a removal
      efficiency of 92.9%. When the inlet nitrite concentration was higher, the
      recirculation of the gas from the top of the anoxic reactor was successful to
      enhance the nitrite removal, achieving a NO2- elimination efficiency of 98.3%.

PMID- 29223869
TI  - Nonlinear recurrent neural networks for finite-time solution of general time
      varying linear matrix equations.
AB  - In order to solve general time-varying linear matrix equations (LMEs) more
      efficiently, this paper proposes two nonlinear recurrent neural networks based on
      two nonlinear activation functions. According to Lyapunov theory, such two
      nonlinear recurrent neural networks are proved to be convergent within finite
      time. Besides, by solving differential equation, the upper bounds of the finite
      convergence time are determined analytically. Compared with existing recurrent
      neural networks, the proposed two nonlinear recurrent neural networks have a
      better convergence property (i.e., the upper bound is lower), and thus the
      accurate solutions of general time-varying LMEs can be obtained with less time.
      At last, various different situations have been considered by setting different
      coefficient matrices of general time-varying LMEs and a great variety of computer
      simulations (including the application to robot manipulators) have been conducted
      to validate the better finite-time convergence of the proposed two nonlinear
      recurrent neural networks.

PMID- 29223870
TI  - Validation of an algorithm to detect severe MS relapses in administrative health
      databases.
AB  - BACKGROUND: Severe relapses that required treatment were important outcomes in
      the sentinel trials of disease-modifying therapy (DMT). Identifying such relapses
      in administrative data would allow comparative-effectiveness studies of DMTs to
      be conducted in real-world clinical settings. METHODS: All relapsing-remitting
      (RRMS) and secondary-progressive (SPMS) patients living in Manitoba between 1999
      and 2015 were identified using a validated case definition and linkage to the
      Manitoba MS Clinic database. All healthcare interactions potentially due to
      relapses were extracted from population-based administrative (hospital, physician
      claims and prescription) databases. These "relapse markers" included varying
      thresholds of outpatient prednisone scripts, day hospital or emergency room (ER)
      codes for intravenous (IV) methylprednisolone therapy, family physician,
      neurologist or ER physician billing codes and hospital admissions due to MS.
      Algorithms using combinations of these markers were compared with a reference
      standard of neurologist-defined relapses. The most useful algorithms were also
      examined on a biannual basis over the study period to assess for trends in the
      sensitivity of relapse detection. RESULTS: 1131 participants with RRMS or SPMS
      were linked to administrative databases. Analysis of potential relapse markers
      over the whole 1999-2015 time period was limited by inconsistent coding of same
      day or ER admissions for IV methylprednisolone administration. Widespread
      adoption of high-dose oral outpatient prednisone for relapses since 2009 resulted
      in a progressive improvement in relapse marker sensitivity. The best algorithm
      consisted of oral prednisone prescriptions >50mg/day for 3-60 days and same day
      hospital or ER assessment codes with MS as the most responsible diagnosis
      (sensitivity 70%, specificity 100%, PPV 100%, NPV 96%, kappa 0.8 in 2013-2015).
      CONCLUSIONS: Severe relapses can be identified from administrative datasets with
      reasonable accuracy. The trend since 2009 toward outpatient relapse treatment
      will improve the sensitivity of relapse detection with longitudinal follow-up of
      this cohort and will allow comparison of severe relapse rates between different
      DMTs, supporting future comparative effectiveness studies.

PMID- 29223872
TI  - Relationship between thrombus age in aspirated coronary material and mid-term
      major adverse cardiac and cerebrovascular events in patients with acute
      myocardial infarction.
AB  - BACKGROUND AND AIMS: Recent studies have shown that coronary thrombus
      histopathology is associated with impaired myocardial reperfusion and poor
      clinical outcome in patients with acute myocardial infarction (AMI). We sought to
      investigate the age of thrombi aspirated during percutaneous coronary
      intervention (PCI) in patients with AMI and evaluate the relationship between
      histopathologic findings and major adverse cardiac and cerebrovascular events
      (MACCEs) defined as all-cause death, stroke, or myocardial infarction within 6
      months of PCI. METHODS: In this prospective 2-center observational study,
      coronary material was obtained during PCI from 305 patients with AMI within 24 h
      of symptom onset. Thrombi were morphologically classified as either only fresh or
      older (lytic changes or organization). RESULTS: MACCE occurred in 38 (12.5%)
      patients. Only fresh thrombi were observed in 114 (37%) of 305 patients; older
      thrombi were identified in 191 (63%). The rate of MACCE was significantly higher
      among patients with older thrombus (p = 0.011). Multivariate analysis also showed
      the presence of older thrombus [odds ratio (OR) 3.03, 95% confidence interval
      (CI) 1.122-9.522] is an independent predictor of MACCE within 6 months of PCI, as
      well as age (OR 1.051, 95% CI 1.013-1.094) and creatine kinase concentration (OR
      1.025, 95% CI 1.013-1.037). The prevalence of slow flow or distal embolization
      during PCI and peak creatine kinase concentration were significantly higher in
      the older thrombus group (p < 0.05, respectively). CONCLUSIONS: Older thrombus
      found in aspirated coronary material is associated with impaired myocardial
      reperfusion and is an independent predictor of mid-term MACCE in patients with
      AMI.

PMID- 29223871
TI  - Intensity ratio to improve black hole assessment in multiple sclerosis.
AB  - BACKGROUND: Improved imaging methods are critical to assess neurodegeneration and
      remyelination in multiple sclerosis. Chronic hypointensities observed on T1
      weighted brain MRI, "persistent black holes," reflect severe focal tissue damage.
      Present measures consist of determining persistent black holes numbers and
      volumes, but do not quantitate severity of individual lesions. OBJECTIVE: Develop
      a method to differentiate black and gray holes and estimate the severity of
      individual multiple sclerosis lesions using standard magnetic resonance imaging.
      METHODS: 38 multiple sclerosis patients contributed images. Intensities of
      lesions on T1-weighted scans were assessed relative to cerebrospinal fluid
      intensity using commercial software. Magnetization transfer imaging, diffusion
      tensor imaging and clinical testing were performed to assess associations with
      T1w intensity-based measures. RESULTS: Intensity-based assessments of T1w
      hypointensities were reproducible and achieved > 90% concordance with expert
      rater determinations of "black" and "gray" holes. Intensity ratio values
      correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor
      imaging metrics (R values ranging from 0.283 to -0.531) that have been associated
      with demyelination and axon loss. Intensity ratio values incorporated into T1w
      hypointensity volumes correlated with clinical measures of cognition.
      CONCLUSIONS: This method of determining the degree of hypointensity within
      multiple sclerosis lesions can add information to conventional imaging.

PMID- 29223873
TI  - Molecular characterization and expression profiles of LPXRFa at the brain
      pituitary-gonad axis of half-smooth tongue sole (Cynoglossus semilaevis) during
      ovarian maturation.
AB  - Gonadotropin-inhibitory hormone (GnIH) has been characterized by its ability to
      inhibit either basal or gonadotropin-releasing hormone (GnRH)-induced
      gonadotropin synthesis and release in birds and mammals. However, the
      physiological role of GnIH on the reproductive axis in fish remains inconclusive,
      with most studies focusing on the orders Cypriniformes and Perciformes. To gain
      insight into the role of GnIH in the regulation of reproduction in the order
      Pleuronectiformes, we first cloned the LPXRFa gene, the piscine ortholog of GnIH,
      in the half-smooth tongue sole. The full-length cDNA of LPXRFa was 918bp in size
      with an open reading frame (ORF) of 585bp that encoded a 194 amino acids
      preprohormone with a calculated molecular mass and isoelectric point of 21.73kDa
      and 6.52, respectively. The LPXRFa precursor encoded two putative peptide
      sequences that included -MPMRF or -MPQRF motifs at the C-terminal. Tissue
      distribution analysis showed that LPXRFa transcripts could be detected at high
      levels in the brains of both sexes and to a lesser extent in the ovary, heart and
      stomach of females, while a noteworthy expression was observed in the kidney and
      muscle of males. Furthermore, the expression patterns of LPXRFa mRNA during
      ovarian maturation were also investigated. In the brain, the mRNA expression of
      LPXRFa increased significantly at stage III, declined at stage V and reached a
      maximum at stage VI. In the pituitary, the levels of LPXRFa mRNA remained stable
      during ovarian maturation and increased significantly to the top level at stage V
      and then declined back to basal levels. In contrast, the ovarian LPXRFa mRNA
      levels declined sharply at stage III and remained depressed over the course of
      ovarian maturation. Taken together, our results provide further evidence for the
      existence of LPXRFa in the order Pleuronectiformes and suggest its possible
      involvement in the regulation of reproduction in the female tongue sole.

PMID- 29223874
TI  - The hypoxia-tolerant vertebrate brain: Arresting synaptic activity.
AB  - The ion channel arrest hypothesis has been the foundation of three decades of
      research into the underlying mechanisms of hypoxia/anoxia tolerance in several
      key species, including: painted turtles, goldfish, crucian carp, naked mole rats,
      and arctic and ground squirrels. The hypothesis originally stated that
      hypoxia/anoxia tolerant species ought to have fewer ion channels per area
      membrane and/or mechanisms to regulate the conductance of ion channels. Today we
      can add to this and include mechanisms to remove channels from membranes and the
      expression of low conductance isoforms. Furthermore, possible oxygen sensing
      mechanisms in brain include a link to mitochondrial function, changes in the
      concentration of intracellular Ca2+ and reactive oxygen species, and activation
      of protein kinase C and a phosphatase. Importantly ion channel arrest leads to a
      decrease in metabolic rate that is fundamental to survival without oxygen and in
      brain is reflected in decreased action potential frequency or spike arrest. This
      results not only from a decrease in excitatory glutamatergic receptor currents
      but also by an increase in inhibitory GABAergic receptor currents. The surprising
      finding that ionic conductance through some ion channels increases is novel and
      contrary to the ion channel arrest hypothesis. The major insight that this offers
      is that key regulatory events are occurring at the level of the synapse and we
      therefore propose the "synaptic arrest hypothesis".

PMID- 29223875
TI  - Snakes exhibit tissue-specific variation in cardiotonic steroid sensitivity of
      Na+/K+-ATPase.
AB  - Toads are among several groups of organisms chemically defended with lethal
      concentrations of cardiotonic steroids. As a result, most predators that prey on
      amphibians avoid toads. However, several species of snakes have gained resistance
      conferring mutations of Na+/K+-ATPase, the molecular target of cardiotonic
      steroids, and can feed on toads readily. Despite recent advances in our
      understanding of this adaptation at the genetic level, we have lacked functional
      evidence for how mutations of Na+/K+-ATPase account for cardiotonic steroid
      resistance in snake tissues. To address this issue, it is necessary to determine
      how the Na+/K+-ATPases of snakes react to the toxins. Some tissues might have
      Na+/K+-ATPases that are more susceptible than others and can thus provide clues
      about how the toxins influence organismal function. Here we provide a mechanistic
      link between observed Na+/K+-ATPase substitutions and observed resistance using
      actual snake Na+/K+-ATPases. We used an in vitro approach to determine the tissue
      specific levels of sensitivity to cardiotonic steroids in select resistant and
      non-resistant snakes. We compared the sensitivities of select tissues within and
      between species. Our results suggest that resistant snakes contain highly
      resistant Na+/K+-ATPases in their heart and kidney, both of which rely heavily on
      the enzymes to function, whereas tissues that do not rely as heavily on Na+/K+
      ATPases or might be protected from cardiotonic steroids by other means (liver,
      gut, and brain) contain non-resistant forms of the enzyme. This study reveals
      functional evidence that tissue-level target-site insensitivity to cardiotonic
      steroids varies not only among species but also across tissues within resistant
      taxa.

PMID- 29223876
TI  - Joint moments required to hold a posture while somersaulting.
AB  - A pure somersault is a key skill in diving and gymnastics, and involves rotation
      about the transverse axis of the body. As the rotational speed increases the
      effort required to maintain a specified posture increases. This paper derives
      equations for the joint moments required for an athlete to hold three sport
      specific postures as a function of rotational speed. The joint moment is related
      to the isometric muscular strength and is the limiting factor of an athlete in
      their ability to hold a fixed posture while somersaulting. One inertial property
      data set was used to explore the joint moments required for three sport specific
      postures -tuck, pike and layout-. Even though the joint moments are proportional
      to the square of angular velocity, the constant of proportionality differs for
      each joint, and so greater isometric strength is required at some joints;
      especially the hips and through the torso. The situation when the hands were
      allowed to hold the legs and when they did not has been considered. It was found
      that the arms holding an observed point on the lower legs could reduce the joint
      moments required through the legs and torso. The direction of the pull of the
      hands against the legs is critical for effectiveness. For the tuck this included
      a large component tangential to the shank and so emphasises the need to maximise
      friction between the shank and hands. For the pike the pull normal to the shank
      was more important.

PMID- 29223877
TI  - Transcriptomic analyses reveal complex and interconnected sucrose signaling
      cascades in developing seeds of castor bean.
AB  - Seeds are highly specific organs that strongly sink sucrose resources from leaf
      and stem tissues to trigger seed metabolism and development. In particular, for
      heterotrophic non-green seeds, the potential molecular mechanism underlying
      sucrose-driven seed development remains unanswered. Castor bean (Ricinus communis
      L.), a typical non-green seed, has been considered as a model plant for seed
      biology study in dicotyledonous plants due to its heterotrophic seeds with
      persistent endosperms. In the present study, the fast-developing castor bean
      seeds were treated with exogenous sucrose and mannitol for four hours. The global
      transcriptomic data were obtained by high-throughput RNA-seq technique, resulting
      in 468 differentially expressed genes (DGEs). Further analyses revealed that
      sucrose functioned as both metabolic substrates and signal molecules.
      Specifically, 73 DGEs involved in carbohydrate and nitrogen metabolism, 42
      differentially expressed transcription factors, and 35 DGEs involved in diverse
      signaling pathways such as auxin, brassinosteroid, ethelyene, cytokinin,
      gibberellin, and calcium signals, were identified, suggesting that the sucrose
      signaling pathway might have complex and multi-connected cross-talks with other
      signals to regulate castor bean seed development. Taken together, this study
      provides novel data to improve understanding of the potential molecular
      mechanisms of sucrose in regulating non-green seed development and storage
      reservoir accumulation during seed development.

PMID- 29223878
TI  - Constitutive gibberellin response in grafted tomato modulates root-to-shoot
      signaling under drought stress.
AB  - Plants are sessile organisms that must perceive and respond to various
      environmental constraints throughout their life cycle. Among these constraints,
      drought stress has become the main limiting factor to crop production around the
      world. Water deprivation is perceived primarily by the roots, which efficiently
      signal the shoot to trigger drought responses in order to maximize a plant's
      ability to survive. In this study, the tomato (Solanum lycopersicum L.) mutant
      procera (pro), with a constitutive response to gibberellin (GA), and its near
      isogenic line cv. Micro-Tom (MT), were used in reciprocal grafting under well
      watered and water stress conditions to evaluate the role of GA signaling in root
      to-shoot communication during drought stress. Growth, oxidative stress, gene
      expression, water relations and hormonal content were measured in order to
      provide insights into GA-mediated adjustments to water stress. All graft
      combinations with pro (i.e. pro/pro, MT/pro and pro/MT) prevented the reduction
      of growth under stress conditions without a reduction in oxidative stress. The
      increase of oxidative stress was followed by upregulation of SlDREB2, a drought
      tolerance related gene, in all drought-stressed plants. Scions harboring the pro
      mutation tended to increase the abscisic acid (ABA) content, independent of the
      rootstock. Moreover, the GA sensitivity of the rootstock modulated stomatal
      conductance and water use efficiency under drought stress, indicating GA and ABA
      crosstalk in the adjustment of growth and water economy.

PMID- 29223879
TI  - Internalization of a sunflower mannose-binding lectin into phytopathogenic fungal
      cells induces cytotoxicity.
AB  - Lectins are carbohydrate-affinity proteins with the ability to recognize and
      reversibly bind specific glycoconjugates. We have previously isolated a bioactive
      sunflower mannose-binding lectin belonging to the jacalin-related family called
      Helja. Despite of the significant number of plant lectins described in the
      literature, only a small group exhibits antifungal activity and the mechanism by
      which they kill fungi is still not understood. The aim of this work was to
      explore Helja activity on plant pathogenic fungi, and provide insights into its
      mechanism of action. Through cellular and biochemical experimental approaches,
      here we show that Helja exerts an antifungal effect on Sclerotinia sclerotiorum,
      a sunflower pathogen. The lectin interacts with the fungal spore surface,
      permeabilizes its plasma membrane, can be internalized into the cell and induces
      oxidative stress, finally leading to the cell death. On the other hand, Helja is
      inactive towards Fusarium solani, a non-pathogen of sunflower, showing the
      selective action of the lectin. The mechanistic basis for the antifungal activity
      of an extracellular jacalin lectin is presented, suggesting its initial
      interaction with fungal cell wall carbohydrates and further internalization. The
      implication of our findings for plant defense is discussed.

PMID- 29223880
TI  - Tomato plants use non-enzymatic antioxidant pathways to cope with moderate UV-A/B
      irradiation: A contribution to the use of UV-A/B in horticulture.
AB  - Plants developed receptors for solar UV-A/B radiation, which regulate a complex
      network of functions through the plant's life cycle. However, greenhouse grown
      crops, like tomato, are exposed to strongly reduced UV radiation, contrarily to
      their open-field counterparts. A new paradigm of modern horticulture is to
      supplement adequate levels of UV to greenhouse cultures, inducing a positive mild
      stress necessary to stimulate oxidative stress pathways and antioxidant
      mechanisms. Protected cultures of Solanum (cv MicroTom) were supplemented with
      moderate UV-A (1h and 4h) and UV-B (1min and 5min) doses during the
      flowering/fruiting period. After 30days, flowering/fruit ripening synchronization
      were enhanced, paralleled by the upregulation of blue/UV-A and UV-B receptors'
      genes cry1a and uvr8. UV-B caused moreover an increase in the expression of hy5,
      of HY5 repressor cop1 and of a repressor of COP1, uvr8. While all UV-A/B
      conditions increased SOD activity, increases of the generated H2O2, as well as
      lipid peroxidation and cell mebrane disruption, were minimal. However, the
      activity of antioxidant enzymes downstream from SOD (CAT, APX, GPX) was not
      significant. These results suggest that the major antioxidant pathways involve
      phenylpropanoid compounds, which also have an important role in UV screening.
      This hypothesis was confirmed by the increase of phenolic compounds and by the
      upregulation of chs and fls, coding for CHS and FLS enzymes involved in the
      phenylpropanoid synthesis. Overall, all doses of UV-A or UV-B were beneficial to
      flowering/fruiting but lower UV-A/B doses induced lower redox disorders and were
      more effective in the fruiting process/synchronization. Considering the benefits
      observed on flowering/fruiting, with minimal impacts in the vegetative part, we
      demonstrate that both UV-A/B could be used in protected tomato horticulture
      systems.

PMID- 29223881
TI  - Time of return back to work and complications following cross-finger flaps in
      industrial workers: Comparison between immediate post operative mobilization
      versus immobilization until flap division.
AB  - INTRODUCTION: Previous authors have immobilized the injured hand or digits
      following cross finger flaps. PATIENTS AND METHODS: About 3 years ago, the author
      adopted a protocol of immediate postoperative active and passive mobilization
      (without a splint) following cross finger flap surgery in industrial workers. The
      current study is a retrospective audit comparing postoperative complications and
      time of return back to work following cross-finger flaps in two groups of injured
      industrial workers: Group I (n=12) had immediate postoperative mobilization; and
      Group II (n=12) had immobilization till the time of flap division. RESULTS: The
      complication rate was similar in both groups. However, patients in Group I
      returned to work earlier than those in group II and the difference was
      statistically significant. CONCLUSION: Immediate postoperative mobilization
      following cross-finger flaps in industrial workers does not increase the risk of
      complications and has the advantage of early return to work.

PMID- 29223882
TI  - Recurrent renal cancer in Birt-Hogg-Dube syndrome: A case report.
AB  - INTRODUCTION: Birt-Hogg-Dube syndrome (BHDS) is a rare autosomal dominant
      disease. It is caused by constitutional mutations in the FLCN gene. Since BHDS is
      a rare syndrome therefore it is unknown to many physicians. However, it is
      important to identify this rare syndrome at early stages because incidence of
      renal cancer in BHD patients is very high and its detection at early stages can
      prevent its metastasis. Hence, we want to present a case of BHDS and draw the
      attention of the treating physician to this rare inherited disorder and discuss
      its appropriate diagnosis and management. CASE PRESENTATION: We present a case of
      a 50-year old male presented to the consulting clinics of a University Hospital
      with right flank pain since the last 2 months. The Computed Tomography (CT) and
      biopsy on the right renal mass indicated clear cell type renal cell carcinoma
      with significant lymphadenopathy. Past history of cystic lung disease and
      pneumothorax along with positive finding of renal cell carcinoma on CT and biopsy
      suggested Birt-Hogg-Dube (BHD) syndrome. The patient underwent right radical
      nephrectomy and lymph node dissection. His 3 months post- surgery follow up CT
      scan indicated disease recurrence. CONCLUSION: In conclusion, it is important to
      identify this rare syndrome at early stages. Diagnosis for the patients with a
      positive family history for renal cell cancer and pneumothorax should be
      considered. FLCN sequencing should also be taken into account in patients and
      their families because incidence of renal cancer in BHD patients is very high and
      detection at early stages can prevent its metastasis.

PMID- 29223883
TI  - Analysis of mainland Japanese and Okinawan Japanese populations using the
      precision ID Ancestry Panel.
AB  - We typed 165 AIMs in 49 mainland Japanese and 47 Okinawa Japanese using the
      Precision ID Ancestry Panel (Thermo Fisher Scientific). None of the 165 SNPs
      showed significant deviation from Hardy-Weinberg equilibrium in the mainland
      Japanese. One SNP (rs3943253) showed significant deviation from Hardy-Weinberg
      equilibrium in Okinawa Japanese. Fisher's exact tests showed that the genotype
      frequencies of 14 loci were significantly different (p<0.05) between the two
      populations before correction for multiple testing. After Bonferroni correction,
      only rs671 remained statistically significant (p<0.0003). This SNP is located in
      the ALDH2 gene. The mutant A allele is associated with increased side effects
      after alcohol intake. The frequency of the GG genotype (wild type) was higher in
      the Okinawa Japanese (78.7%) than in mainland Japanese (34.7%; Bonferroni
      corrected P<0.001). For 31 (63.3%) of the mainland Japanese and 42 (89.4%) of
      Okinawa Japanese, the highest population likelihood was obtained with the
      Japanese reference population. However, only in a few individuals, the
      likelihoods were significantly different from those calculated using reference
      data from neighboring populations. The likelihoods for mainland Japanese and
      Okinawa Japanese were not significantly different from each other for any of the
      investigated individuals. STRUCTURE and PCA analyses showed that mainland
      Japanese, Okinawa Japanese, and East Asians could not be differentiated with the
      Precision ID Ancestry Panel.

PMID- 29223884
TI  - Chronic effect of different types of stretching on ankle dorsiflexion range of
      motion: Systematic review and meta-analysis.
AB  - The calf muscles are one of the muscle groups that have the most need for
      adequate flexibility since they are deeply related to normal lower limb function.
      When the goal is to increase flexibility, the most commonly used technique is
      stretching. However, it remains unknown which stretching technique and parameters
      are the most effective to increase flexibility. Hence, the aim of the current
      review was to investigate the influence of chronic stretching on ankle
      dorsiflexion range of motion (DFROM) of healthy individuals. The search strategy
      included MEDLINE, PEDro, Cochrane CENTRAL, LILACS, and manual search from
      inception to February 2017. Randomized and controlled clinical trials that have
      analyzed the influence of chronic stretching on DFROM were included. On the other
      hand, studies with special populations (children, and people with any
      dysfunction/disease), and articles with no control group were excluded. Twenty
      studies were included out of 493 identified. The meta-analysis was performed
      according to the stretching technique used in the study. The results show that
      static stretching (5.17 degrees ; 95% CI: 4.39-5.95; I2: 0%) and proprioceptive
      neuromuscular facilitation (4.32 degrees ; 95% CI: 1.59-7.04; I2: 46%) are
      effective in increasing DFROM. Ballistic stretching did not show positive results
      to increase DFROM (3.77 degrees ; 95% CI: -0.03 to 7.56; I2: 46%). In conclusion,
      chronic stretching is an effective way of improving ankle mobility in healthy
      individuals, especially when it contains a static component.

PMID- 29223885
TI  - Three novel SLC2A1 mutations in Bulgarian patients with different forms of
      genetic generalized epilepsy reflecting the clinical and genetic diversity of
      GLUT1-deficiency syndrome.
AB  - PURPOSE: GLUT1-deficiency syndrome (GLUT1-DS) is a metabolic brain disorder with
      a great clinical heterogeneity underlined by various mutations in the SLC2A1 gene
      which make the clinical and genetic diagnosis complicated. The purpose of our
      study is to investigate the genetic defects affecting the SLC2A1 gene in a group
      of Bulgarian patients with genetic generalized epilepsy (GGE), and to bring new
      insights into the molecular pathology of GLUT1-DS that would strengthen the
      genotype-phenotype correlations and improve the diagnostic procedure. METHODS: We
      have performed sequencing analysis of the SLC2A1 gene in thirty-eight Bulgarian
      patients with different forms of GGE having emerged in childhood followed by
      array comparative genome (aCGH) hybridization in patients with severe forms of
      GLUT1-DS who display extraneurological features. RESULTS: We have detected three
      novel SLC2A1 gene mutations that are predicted to have different impacts on the
      GLUT1 protein structure and function - one being to cause the amino acid
      substitution p.H160Q, another leading to the truncation p.Q360*, and also a
      1p34.2 microdeletion. The overall frequency of the SLC2A1 mutations in the
      studied group is 8.1%. They have been found in clinical cases that differ notably
      by their severity. CONCLUSION: Our study enriches the mutation spectrum of the
      SLC2A1 gene by 3 novel cases that reflect the genetic and phenotypic diversity of
      GLUT1-DS and brings new insights into the molecular pathology of that disorder.
      The clinical data showed that the SLC2A1 genetic defects should be considered
      equally in the entire range of the clinical manifestations of GGE paying
      attention to the extraneurological features. The aCGH analysis should be
      considered as an ultimate step during the diagnostic procedure of GLUT1-DS in
      patients with a complex clinical picture of intractable epilepsy involving
      neuropsychological impairments and accompanied by extraneurological features.

PMID- 29223888
TI  - Neighborhood crime undermines parenting: Violence in the vicinity of households
      as a predictor of aggressive discipline.
AB  - Child discipline is a central component of parent-child interactions. Evidence
      suggests corporal discipline impairs children's physical, cognitive, and
      socioemotional development and compromises their future chances, especially since
      it is more frequently used against at-risk children. Using geocoded data for 1209
      children under the age of five and their mothers, this study analyses the
      relation between the occurrence of crimes in close proximity to households in
      four major urban municipalities of Colombia and a particularly violent corporal
      discipline practice: hitting children with objects. Results indicate that
      exposure to violent crimes, such as homicides and personal injuries, predicts a
      higher probability of hitting children with objects, even after controlling for a
      set of individual, family, and neighborhood characteristics. Sensitivity analyses
      suggest violent crimes are not related to other discipline methods, and less
      threatening crimes, such as robbery and drug trafficking, are not associated with
      hitting children with objects. These findings suggest households' walls are
      permeable, and outside threats may interfere with families' dynamics and well
      being. Future directions and implications are discussed.

PMID- 29223886
TI  - Electrocatalytic CO2 reduction catalyzed by nitrogenase MoFe and FeFe proteins.
AB  - Nitrogenases catalyze biological dinitrogen (N2) reduction to ammonia (NH3), and
      also reduce a number of non-physiological substrates, including carbon dioxide
      (CO2) to formate (HCOO-) and methane (CH4). Three versions of nitrogenase are
      known (Mo-, V-, and Fe-nitrogenase), each showing different reactivities towards
      various substrates. Normally, electrons for substrate reduction are delivered by
      the Fe protein component of nitrogenase, with energy coming from the hydrolysis
      of 2 ATP to 2 ADP+2 Pi for each electron transferred. Recently, it has been
      demonstrated that energy and electrons can be delivered from an electrode to the
      catalytic nitrogenase MoFe-protein without the need for Fe protein or ATP
      hydrolysis. Here, it is demonstrated that both the MoFe- and FeFe-protein can be
      immobilized as a polymer layer on an electrode and that electron transfer
      mediated by cobaltocene can drive CO2 reduction to formate in this system. It was
      also found that the FeFe-protein diverts a greater percentage of electrons to CO2
      reduction versus proton reduction compared to the MoFe-protein. Quantification of
      electron flow to products exhibited Faradaic efficiencies of CO2 conversion to
      formate of 9% for MoFe protein and 32% for FeFe-protein, with the remaining
      electrons going to proton reduction to make H2.

PMID- 29223887
TI  - A minimalistic approach to develop new anti-apicomplexa polyamines analogs.
AB  - The development of new chemical entities against the major diseases caused by
      parasites is highly desired. A library of thirty diamines analogs following a
      minimalist approach and supported by chemoinformatics tools have been prepared
      and evaluated against apicomplexan parasites. Different member of the series of
      N,N'-disubstituted aliphatic diamines shown in vitro activities at submicromolar
      concentrations and high levels of selectivity against Toxoplasma gondii and in
      chloroquine-sensitive and resistant-strains of Plasmodium falciparum. In order to
      demonstrate the importance of the secondary amines, ten N,N,N',N'
      tetrasubstituted aliphatic diamines derivatives were synthesized being
      considerably less active than their disubstituted counterpart. Theoretical
      studies were performed to establish the electronic factors that govern the
      activity of the compounds.

PMID- 29223889
TI  - From dead leaves to sustainable organic resistive switching memory.
AB  - An environmental-friendly, sustainable, pollution-free, biodegradable, flexible
      and wearable electronic device hold advanced potential applications. Here, an
      organic resistive switching memory device with Ag/Leaves/Ti/PET structure on a
      flexible polyethylene terephthalate (PET) substrate was fabricated for the first
      time. We observed an obvious resistive switching memory characteristic with large
      switching resistance ratio and stable cycle performance at room temperature. This
      work demonstrates that leaves, a useless waste, can be properly treated to make
      useful devices. Furthermore, the as-fabricated devices can be degraded naturally
      without damage to the environment.

PMID- 29223890
TI  - Gold core/ceria shell-based redox active nanozyme mimicking the biological
      multienzyme complex phenomenon.
AB  - Catalytically active individual gold (Au) and cerium oxide (CeO2) nanoparticles
      (NPs) are well known to exhibit specific enzyme-like activities, such as natural
      catalase, oxidase, superoxide dismutase, and peroxidase enzymes. These activities
      have been maneuvered to design several biological applications such as
      immunoassays, glucose detection, radiation and free radical protection and tissue
      engineering. In biological systems, multienzyme complexes are involved in
      catalyzing important reactions of essential metabolic processes such as
      respiration, biomolecule synthesis, and photosynthesis. It is well known that
      metabolic processes linked with multienzyme complexes offer several advantages
      over reactions catalyzed by individual enzymes. A functional nanozyme depicting
      multienzyme like properties has eluded the researchers in the nanoscience
      community for the past few decades. In the current report, we have designed a
      functional multienzyme in the form of Gold (core)-CeO2 (shell) nanoparticles
      (Au/CeO2 CSNPs) exhibiting excellent peroxidase, catalase, and superoxide
      dismutase enzyme-like activities that are controlled simply by tuning the pH. The
      reaction kinetic parameters reveal that the peroxidase-like activity of this core
      shell nanozyme is comparable to natural horseradish peroxidase (HRP) enzyme.
      Unlike peroxidase-like activity exhibited by other nanomaterials, Au/CeO2 CSNPs
      showed a decrease in hydroxyl radical formation, suggesting that the biocatalytic
      reactions are performed by efficient electron transfers. A significant enzyme
      like activity of this core-shell nanoparticle was conserved at extreme pH (2-11)
      and temperatures (up to 90  degrees C), clearly suggesting the superiority over
      natural enzymes. Further, the utility of peroxidase-like activity of this core
      shell nanoparticles was extended for the detection of glucose, which showed a
      linear range of detection between (100 uM to 1 mM). It is hypothesized that the
      proximity of the redox potentials of Au+/Au and Ce (III)/Ce (IV) may result in a
      redox couple promoting the multienzyme activity of core-shell nanoparticles.
      Au/CeO2 CSNPs may open new directions for development of single platform sensors
      in multiple biosensing applications.

PMID- 29223891
TI  - Fallen leaves derived honeycomb-like porous carbon as a metal-free and low-cost
      counter electrode for dye-sensitized solar cells with excellent tri-iodide
      reduction.
AB  - Utilizing carbon-based counter electrodes (CEs) in dye-sensitized solar cells
      (DSSCs) have received much attention in recent times, owing to their low cost,
      good electrochemical activity, natural abundance and eco-friendly nature. Herein,
      we have facilely prepared quince leaves derived porous carbon (QLPC) using fallen
      quince leaves (QLs) and it was used as a cost-effective CE for the fabrication of
      DSSCs. By means of alkali treatment and pyrolysis process (at different
      temperatures of 700, 800 and 900  degrees C), the QLs powder undergoes chemical
      activation and carbonization, which results in a honeycomb-like QLPC with
      abundant micro/mesopores and large surface area. Simple and straightforward
      coating of QLPC samples onto fluorine doped tin oxide glass substrates led to
      improved electrocatalytic activity and good tri-iodide reduction in DSSCs. When
      the DSSCs were illuminated under 1 sun condition (AM 1.5; 100 mW cm-2), the
      device assembled with QLPC-based CE (prepared at 800  degrees C) showed a higher
      current density of ~14.99 mA/cm2 and power conversion efficiency of ~5.52% among
      the other QLPC-based CEs, which are comparable with the platinum-based CE in
      DSSCs. This facile process for the preparation of biomass derived carbon-based CE
      provides an alternative to the noble metal-free CE in DSSCs.

PMID- 29223892
TI  - Liquid chromatography quadrupole time-of-flight mass spectrometry determination
      of six pharmaceuticals in vegetal biota. Uptake study in Lavandula dentata.
AB  - A procedure based on microwave assisted extraction for the determination of 6
      pharmaceuticals in samples of Lavandula dentata, Salicornia ramosissima and
      Juncus sp. by liquid chromatography-quadrupole time of flight mass spectrometry
      (LC-QTOF/MS) was optimized and validated. Best results were obtained using
      microwave assisted extraction of 1.0g of homogeneous lyophilized samples and 5mL
      of a mixture ACN:H2O (1:1 v/v) as extracting solvent. Analytical recoveries
      ranged from 60 to 107% with relative standard deviation (RSD) lower than 15%.
      Limits of quantitation (LOQ) for the 6 pharmaceuticals flumequine (FLM),
      carbamazepine (CBZ), ciprofloxacin (CPR), enrofloxacin (ENR), diclofenac (DCL),
      and ibuprofen (IBU) were in the range 20.8-125ngg-1. The method was satisfactory
      applied for an uptake study in Lavandula dentata samples finding quantifying
      concentrations of FLM and CBZ in roots, leaf and stem.

PMID- 29223893
TI  - Biogeographic distribution of bacterial, archaeal and methanogenic communities
      and their associations with methanogenic capacity in Chinese wetlands.
AB  - Natural wetlands and anthropogenic paddy fields are the dominant biogenic sources
      of atmospheric methane emission which have been speculated as the most probable
      sources for the increase of post-2006 atmospheric methane. Regional differences
      in CH4 emission is possibly due to microbial biogeographic distribution. Here we
      collected soils from 19 wetlands from different regions in China. The methane
      production capacity (MPC) was measured for each soil samples and varied from 1.11
      to 841.94mg/kg dry soil. High throughput sequencing was employed to investigate
      the diversity and composition of bacterial, archaeal and methanogenic
      communities. Similar biogeographic patterns for bacterial, archaeal and
      methanogenic communities along the latitudinal gradient were observed, and the
      biogeographic assemblies of different microbial groups were driven by concurrent
      factors, including edaphic variables (total organic carbon, total phosphorus and
      pH) and climatic variables (annual frost days, mean annual temperature, direct
      solar radiation and mean annual precipitation). MPC was significantly correlated
      with TOC concentration, and in addition, various functional taxa were positively
      correlated with MPC (P<0.05), for example, Sphingomonas, Syntrophomonas,
      Methanospirillum and Methanoregula, indicating their potential contributions in
      the methanogenic process, and many of them were fermentative bacteria and
      methanogens. Network analysis showed that some syntrophs, sulfate-reducers and
      methanogens were tightly co-occurred in one module, suggesting their involvements
      in cross-linked functional processes. Our study implicated both temperature and
      substrate availability altered the biogeographic patterns of microbial community
      as well as methane production potential in Chinese wetlands.

PMID- 29223894
TI  - A model-based fish bioassessment index for Eastern Mediterranean rivers:
      Application in a biogeographically diverse area.
AB  - In ecosystems with high fish species endemicity, such as Mediterranean-type
      rivers, biogeographical differences among ecoregions present serious obstacles to
      developing broadly-applicable river bioassessment indices. This impediment has
      contributed to a serious time-lag in developing EU policy-relevant fish-based
      indices in the Eastern Mediterranean countries. Here we present the first model
      based fish index for the Eastern Mediterranean (the Hellenic Fish Index, HeFI) in
      an effort to overcome biogeographic differences among the area's biotically
      heterogeneous rivers. The index is based on modelled reference conditions and
      employs site-specific electrofished fish samples from an extensive dataset from
      Greece that covers six freshwater ecoregions, including five transboundary river
      basins flowing through six countries. Environmental and anthropogenic pressure
      data were procured from 403 sampled river sites and ecologically-relevant traits
      were defined for 103 collected fish species. For the development of the index, we
      first diagnosed least degraded sites forming a calibrated reference site dataset
      and secondly quantified differences of fish metrics between the reference and
      impaired sites. Four trait-based fish metrics showed the best ability to
      discriminate between impaired and reference sites. The index performed well in
      discriminating anthropogenic pressure classes, giving a significant negative
      linear response to a gradient of anthropogenic degradation. HeFI successfully
      assessed both small and large rivers in different freshwater ecoregions. This
      geographically broad-scale index development shows that key trait-based reference
      conditions can be produced by a predictive model in remarkably heterogeneous
      rivers where range-restricted fishes dominate. This index promotes a screening
      level bioassessment application that may be further developed and refined with
      relevant monitoring.

PMID- 29223895
TI  - Effects of land use and sampling distance on water quality in tropical headwater
      springs (Pimenta creek, Sao Paulo State, Brazil).

PMID- 29223896
TI  - Environmental status of livestock and poultry sectors in China under current
      transformation stage.
AB  - Intensive animal husbandry had aroused great environmental concerns in many
      developed countries. However, some developing countries are still undergoing the
      environmental pollution from livestock and poultry sectors. Driven by the large
      demand, China has experienced a remarkable increase in dairy and meat production,
      especially in the transformation stage from conventional household breeding to
      large-scale industrial breeding. At the same time, a large amount of manure from
      the livestock and poultry sector is released into waterbodies and soil, causing
      eutrophication and soil degradation. This condition will be reinforced in the
      large-scale cultivation where the amount of manure exceeds the soil nutrient
      capacity, if not treated or utilized properly. Our research aims to analyze
      whether the transformation of raising scale would be beneficial to the
      environment as well as present the latest status of livestock and poultry sectors
      in China. The estimation of the pollutants generated and discharged from
      livestock and poultry sector in China will facilitate the legislation of manure
      management. This paper analyzes the pollutants generated from the manure of the
      five principal commercial animals in different farming practices. The results
      show that the fattening pigs contribute almost half of the pollutants released
      from manure. Moreover, the beef cattle exert the largest environmental impact for
      unitary production, about 2-3 times of pork and 5-20 times of chicken. The
      animals raised with large-scale feedlots practice generate fewer pollutants than
      those raised in households. The shift towards industrial production of livestock
      and poultry is easier to manage from the environmental perspective, but adequate
      large-scale cultivation is encouraged. Regulation control, manure treatment and
      financial subsidies for the manure treatment and utilization are recommended to
      achieve the ecological agriculture in China.

PMID- 29223897
TI  - Agricultural drought prediction using climate indices based on Support Vector
      Regression in Xiangjiang River basin.
AB  - Drought can have a substantial impact on the ecosystem and agriculture of the
      affected region and does harm to local economy. This study aims to analyze the
      relation between soil moisture and drought and predict agricultural drought in
      Xiangjiang River basin. The agriculture droughts are presented with the
      Precipitation-Evapotranspiration Index (SPEI). The Support Vector Regression
      (SVR) model incorporating climate indices is developed to predict the
      agricultural droughts. Analysis of climate forcing including El Nino Southern
      Oscillation and western Pacific subtropical high (WPSH) are carried out to select
      climate indices. The results show that SPEI of six months time scales (SPEI-6)
      represents the soil moisture better than that of three and one month time scale
      on drought duration, severity and peaks. The key factor that influences the
      agriculture drought is the Ridge Point of WPSH, which mainly controls regional
      temperature. The SVR model incorporating climate indices, especially ridge point
      of WPSH, could improve the prediction accuracy compared to that solely using
      drought index by 4.4% in training and 5.1% in testing measured by Nash Sutcliffe
      efficiency coefficient (NSE) for three month lead time. The improvement is more
      significant for the prediction with one month lead (15.8% in training and 27.0%
      in testing) than that with three months lead time. However, it needs to be
      cautious in selection of the input parameters, since adding redundant information
      could have a counter effect in attaining a better prediction.

PMID- 29223898
TI  - Exposure to low concentrations of air pollutants and adverse birth outcomes in
      Brisbane, Australia, 2003-2013.
AB  - BACKGROUND: It's unclear whether exposures to low-level air pollution have
      adverse effects on birth outcomes, and which trimester-specific pregnant exposure
      is sensitive. OBJECTIVES: To investigate the effects of maternal exposure during
      each trimester and the whole pregnancy to particles with aerodynamic
      diameter<2.5MUm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone
      (O3) on preterm birth (PTB) and low birth weight (LBW). METHODS: Daily data on
      birth records, air quality, and weather conditions were collected in Brisbane,
      Australia during 2003-2013. Mean concentrations of air pollutants were calculated
      for each trimester of pregnancy. Cox proportional hazards models were used to
      examine the associations between air pollution and birth outcomes. Multi
      pollutant models and stratified analyses by ambient temperature were performed.
      RESULTS: Exposures to PM2.5, SO2, NO2, and O3 during the whole pregnancy were
      associated with increased risk of PTB [IQR HRs (hazard ratios with an
      interquartile range increase in air pollutants) and 95% confidence intervals
      (CIs): 1.05 (1.02, 1.08), 1.12 (1.09, 1.16), 1.07 (1.01, 1.13), and 1.13 (1.10,
      1.16), respectively] and LBW [IQR HRs and 95% CIs: 1.06 (1.02, 1.10), 1.12 (1.08,
      1.16), 1.11 (1.03, 1.18), and 1.13 (1.09, 1.17), respectively]. Highest HRs were
      observed during trimester 3, and lowest in trimester 1. For each air pollutant,
      stronger effects on PTB and LBW were present for exposure to low and moderate
      temperatures than exposure to high ambient temperature. CONCLUSIONS: Exposures to
      low-level air pollutants are related to adverse birth outcomes. More effective
      policies for air quality control could contribute to improving neonatal health.

PMID- 29223899
TI  - Nighttime NOx loss and ClNO2 formation in the residual layer of a polluted
      region: Insights from field measurements and an iterative box model.
AB  - The heterogeneous reaction of dinitrogen pentoxide (N2O5) on aerosols is an
      important sink of nitrogen oxides (NOx) in the polluted boundary layer, and the
      production of nitryl chloride (ClNO2) can have significant effects on the
      atmospheric oxidative capacity. However, the heterogeneous loss of N2O5 and the
      formation of ClNO2 are still not well quantified, especially in China. In a
      previous study, we measured ClNO2 and N2O5 concentrations in several air masses
      at a high-elevation site in Hong Kong, and found the highest levels ever reported
      at one night. The present study employed an iterative box model to investigate
      five N2O5/ClNO2-laden nights. We first estimated the N2O5 uptake coefficient and
      ClNO2 yield and then calculated the relative importance of N2O5 heterogeneous
      reactions to NOx loss and the accumulated ClNO2 production over the entire night.
      The average uptake coefficient was 0.004+/-0.003, and the average yield was
      0.42+/-0.26. As the air masses aged, the accumulated ClNO2 reached up to 6.0ppbv,
      indicating significant production of ClNO2 in the polluted air from the Pearl
      River Delta. ClNO2 formation (N2O5+Cl-), N2O5 hydrolysis (N2O5+H2O), and NO3
      reactions with volatile organic compounds (NO3+VOCs) consumed 23%, 27%, and 47%
      of the produced NO3, respectively, as the average for five nights. A significant
      portion of the NOx in the air masses (70%+/-10%) was removed during the night via
      NO3 reactions with VOCs (~40%) and N2O5 heterogeneous loss (~60%).

PMID- 29223900
TI  - Driving factors of soil carbon accumulation in Oxisols in long-term no-till
      systems of South Brazil.
AB  - In a climate change scenario, it is important to understand the factors that lead
      to changes in a soil carbon (C) sink. It is recognized that such process is
      highly dependent on climate, soil properties, topography, and vegetation.
      However, few studies demonstrate how these mechanisms operate in highly weathered
      Oxisols. Therefore, this study evaluated the driving factors for C recovery and
      accumulation and its relations with fertility attributes in the soil profile (0
      to 1m depth) in no-till (NT) croplands of south Brazil. The adoption of NT in the
      studied fields started between 1978 (pioneer areas) and 1990 and represent a
      range of textural and mineralogical characteristics South Brazil main croplands.
      Soil samples were collected in paired fields of native vegetation and NT (NV vs.
      long-term NT) to a depth of 1m. The studied NT areas of Rio Grande do Sul State
      were managed according to the principles of conservation agriculture (minimum
      soil disturbance, permanent soil cover and diverse crop rotation). The processes
      that drove SOC recovery in the studied sites were soil fertility management
      allied with high C input through intense crop rotation. The C recovery was were
      for areas with the predominance of soybean in the cropping system, higher levels
      of Al3+ and lower levels of Mg2+ and P. Sites with medium/high cropping
      intensity, lower levels of Al3+ and higher levels of P, Ca2+, Mg2+, and K+
      resulted in higher C recovery.

PMID- 29223901
TI  - Thermally enhanced in situ bioremediation of groundwater contaminated with
      chlorinated solvents - A field test.
AB  - In situ bioremediation (ISB) using reductive dechlorination is a widely accepted
      but relatively slow approach compared to other technologies for the treatment of
      groundwater contaminated by chlorinated ethenes (CVOCs). Due to the known
      positive kinetic effect on microbial metabolism, thermal enhancement may be a
      viable means of accelerating ISB. We tested thermally enhanced ISB in aquifers
      situated in sandy saprolite and underlying fractured granite. The system
      comprised pumping, heating and subsequent injection of contaminated groundwater
      aiming at an aquifer temperature of 20-30 degrees C. A fermentable substrate
      (whey) was injected in separate batches. The test was monitored using
      hydrochemical and molecular tools (qPCR and NGS). The addition of the substrate
      and increase in temperature resulted in a rapid increase in the abundance of
      reductive dechlorinators (e.g., Dehalococcoides mccartyi, Dehalobacter sp. and
      functional genes vcrA and bvcA) and a strong increase in CVOC degradation. On day
      34, the CVOC concentrations decreased by 87% to 96% in groundwater from the wells
      most affected by the heating and substrate. On day 103, the CVOC concentrations
      were below the LOQ resulting in degradation half-lives of 5 to 6days. Neither an
      increase in biomarkers nor a distinct decrease in the CVOC concentrations was
      observed in a deep well affected by the heating but not by the substrate. NGS
      analysis detected Chloroflexi dechlorinating genera (Dehalogenimonas and GIF9 and
      MSBL5 clades) and other genera capable of anaerobic metabolic degradation of
      CVOCs. Of these, bacteria of the genera Acetobacterium, Desulfomonile, Geobacter,
      Sulfurospirillum, Methanosarcina and Methanobacterium were stimulated by the
      substrate and heating. In contrast, groundwater from the deep well (affected by
      heating only) hosted representatives of aerobic metabolic and aerobic cometabolic
      CVOC degraders. The test results document that heating of the treated aquifer
      significantly accelerated the treatment process but only in the case of an
      abundant substrate.

PMID- 29223902
TI  - People, pollution and pathogens - Global change impacts in mountain freshwater
      ecosystems.
AB  - Mountain catchments provide for the livelihood of more than half of humankind,
      and have become a key destination for tourist and recreation activities globally.
      Mountain ecosystems are generally considered to be less complex and less species
      diverse due to the harsh environmental conditions. As such, they are also more
      sensitive to the various impacts of the Anthropocene. For this reason, mountain
      regions may serve as sentinels of change and provide ideal ecosystems for
      studying climate and global change impacts on biodiversity. We here review
      different facets of anthropogenic impacts on mountain freshwater ecosystems. We
      put particular focus on micropollutants and their distribution and redistribution
      due to hydrological extremes, their direct influence on water quality and their
      indirect influence on ecosystem health via changes of freshwater species and
      their interactions. We show that those changes may drive pathogen establishment
      in new environments with harmful consequences for freshwater species, but also
      for the human population. Based on the reviewed literature, we recommend
      reconstructing the recent past of anthropogenic impact through sediment analyses,
      to focus efforts on small, but highly productive waterbodies, and to collect data
      on the occurrence and variability of microorganisms, biofilms, plankton species
      and key species, such as amphibians due to their bioindicator value for ecosystem
      health and water quality. The newly gained knowledge can then be used to develop
      a comprehensive framework of indicators to robustly inform policy and decision
      making on current and future risks for ecosystem health and human well-being.

PMID- 29223903
TI  - Application rate affects the degradation rate and hence emissions of chloropicrin
      in soil.
AB  - Increasingly stringent regulations to control soil-air emissions of soil
      fumigants has led to much research effort aimed at reducing emission potential.
      Using laboratory soil columns, we aimed to investigate the relationship between
      chloropicrin (CP) application rate and its emissions from soil across a wide
      range of CP applications (equivalent to 56-392kgha-1). In contrast to the known
      behavior of other fumigants, total emission percentages were strongly and
      positively related to application rate (i.e., initial mass), ranging from 4 to
      34% across the application rate range. When combined, data from a previous study
      and the present study showed good overall comparability in terms of CP
      application rate vs. emission percentage, yielding a second-order polynomial
      relationship with an R2 value of 0.93 (n=12). The study revealed that mass losses
      of CP were strongly disproportional to application rate, also showing a
      polynomial relationship. Based on degradation studies, we consider that a shorter
      half-life (faster degradation) at lower application rates limited the amount of
      CP available for emission. The non-linear relationship between CP application
      rate and CP emissions (both as % of that applied and as total mass) suggests that
      low application rates likely lead to disproportionally low emission losses
      compared with higher application rates; such a relationship could be taken into
      account when assessing/mitigating risk, e.g., in the setting of buffer zone
      distances.

PMID- 29223904
TI  - Spatiotemporal variations of hydrogeochemistry and its controlling factors in the
      Gandaki River Basin, Central Himalaya Nepal.
AB  - The characterization and assessment of water quality in the head water region of
      Himalaya is necessary, given the immense importance of this region in sustaining
      livelihoods of people and maintaining ecological balance. A total of 165 water
      samples were collected from 55 sites during pre-monsoon, monsoon and post-monsoon
      seasons in 2016 from the Gandaki River Basin of the Central Himalaya, Nepal. The
      pH, EC values and TDS concentrations were measured in-situ and the concentrations
      of major ions (Ca2+, Mg2+, K+, Na+, Cl-, SO42-, NO3-) and Si were analyzed in
      laboratory. Correlation matrices, paired t-test, cluster analysis, principal
      component analysis (PCA), the Piper, Gibbs, and Mixing plots, and saturation
      index were applied to the measurements for evaluating spatiotemporal variation of
      the major ions. The results reveal mildly alkaline pH values and the following
      pattern of average ionic dominance: Ca2+>Mg2+>Na+>K+ for cations and HCO3->SO42
      >Cl->NO3- for anions. The results of PCA, Gibbs plot and the ionic relationships
      displayed the predominance of geogenic weathering processes in areas with
      carbonate dominant lithology. This conclusion is supported by geochemically
      different water facies identified in the Piper plot as Ca-HCO3 (83.03%), mixed Ca
      Mg-Cl (12.73.0%) and Ca-Cl (4.24%). Pronounced spatiotemporal heterogeneity
      demonstrates the influence of climatic, geogenic and anthropogenic conditions.
      For instance, the Ca2+-SO42-, Mg2+-SO42- and Na+-Cl- pairs exhibit strong
      positive correlation with each other in the upstream region, whereas relatively
      weak correlation in the downstream region, likely indicating the influence of
      evapo-crystallization processes in the upstream region. Analyses of the
      suitability of the water supply for drinking and irrigation reveal that the river
      has mostly retained its natural water quality but poses safety concern at a few
      locations. Knowledge obtained through this study can contribute to the
      sustainable management of water quality in the climatically and lithologically
      distinct segments of the Himalayan river basins.

PMID- 29223905
TI  - Litter removal does not compensate detrimental fire effects on biodiversity in
      regularly burned semi-natural grasslands.
AB  - Regulation of plant biomass accumulation is a key issue in effective grassland
      conservation in Europe. Burning is an alternative tool to regulate biomass
      dynamics in semi-natural grasslands even in the absence of grazing or mowing. We
      tested the effects of regular spring burning on the biomass fractions and fine
      scale plant species composition of species-rich foothill grasslands in North
      Hungary. There were five regularly burned and five control grasslands in the
      study; we collected twenty 20*20-cm sized biomass samples from each. We analyzed
      the main fractions (litter, graminoid and forb biomass), and the species-level
      biomass scores, and flowering success in the control and burned grasslands. We
      revealed that fire increased the amount of forb biomass and decreased the amount
      of litter, which suggested that regular burning might be feasible for regulating
      biomass dynamics. The non-metric multi-dimensional scaling (NMDS) showed a high
      similarity of the control and burned grasslands in species composition. However,
      plant diversity, and the number of flowering shoots decreased significantly in
      the burned grasslands. In regularly burned sites we found a significant decline
      of specialist species, as well as of steppic flora elements. Our results showed
      that besides its positive effect on biomass dynamics, high-frequency burning
      threatens the overall diversity and specialist plant species in semi-natural
      grasslands. We recommend that proper fire regimes should be first studied
      experimentally, to provide a scientific basis for the application of prescribed
      burning management in such habitats.

PMID- 29223906
TI  - Comparison of real-world and certification emission rates for light duty gasoline
      vehicles.
AB  - U.S. light duty vehicles are subject to the U.S. Environmental Protection Agency
      (EPA) emission standards. Emission compliance is determined by certification
      testing of selected emissions from representative vehicles on standard driving
      cycles using chassis dynamometers. Test results are also used in many emission
      inventories. The dynamometer based emission rates are adjusted to provide the
      certification levels (CL), which must be lower than the standards for compliance.
      Although standard driving cycles are based on specific observations of real-world
      driving, they are not necessarily real-world representative. A systematic
      comparison of the real-world emission rates of U.S. light duty gasoline vehicles
      (LDGVs) versus CL, and emission standards has not been previously reported. The
      purpose of this work is to compare regulatory limits (both CLs and emission
      standards) and the real-world emissions of LDGVs. The sensitivity of the
      comparisons to cold start emission was assessed. Portable Emission Measurement
      Systems (PEMS) were used to measure hot stabilized exhaust emissions of 122 LDGVs
      on a specified 110 mile test route. Cold start emissions were measured with PEMS
      for a selected vehicle sample of 32 vehicles. Emissions were measured for carbon
      dioxide (CO2), carbon monoxide (CO), hydrocarbons (HC) and nitrogen oxides (NOx).
      For each vehicle, a Vehicle Specific Power (VSP) modal emission rate model was
      developed. The VSP modal rates were weighted by the standard driving cycles and
      real-world driving cycles to estimate the respective cycle average emission rates
      (CAERs). Measured vehicles were matched with certification test vehicles for
      comparison. For systematic trends in comparison, vehicles were classified into
      four groups based on the Tier 1 and Tier 2 emission regulation, and the vehicle
      type such as passenger car and passenger truck. Depending on the cycle-pollutant
      and the vehicle groups, hot stabilized CAERs are on average either statistically
      significantly higher than or significantly not different from the CLs, with the
      exception of CO on the US06 cycle, for which real-world rates are lower than CLs.
      Compared to the emission standards, hot stabilized CAERs are on average
      significantly lower. However, comparisons of CAERs and standards are sensitive to
      cold start emissions. For some combinations of pollutants and vehicle groups,
      cold start inclusive CAERs are higher than the corresponding CLs and as high as
      the standards. The CLs, which are based on standard driving cycles, tend to
      underestimate real-world emission rates. Therefore, emission inventory estimates
      using certification test results are potentially underestimated.

PMID- 29223907
TI  - Analytical indicators to characterize Particulate Organic Matter (POM) and its
      evolution in French Vertical Flow Constructed Wetlands (VFCWs).
AB  - The design of French VFCWs leads to the formation of a sludge layer at the
      surface of the first filters due to the retention of suspended solids from the
      percolation of unsettled wastewater. This layer plays a major role in the system
      but still little is known on its characteristics and evolutions. In this study,
      suspended solids and sludge deposits sampled from two French VFCW plants were
      analyzed by different methods in the objective to assess the evolution of
      particulate organic matter (POM) along the treatment chain and within the sludge
      layer, and identify relevant analytical indicators of these phenomena. The
      treatment chain included an aerobic trickling filter followed by FeCl3 injection
      and two successive stages of filters. Thermal analyses showed that OM contents of
      suspended solids decreased along the treatment chain. POM in inflow suspended
      solids was predominantly composed of reactive, biodegradable compounds which were
      partly hydrolyzed and mineralized notably at the trickling filter stage. 3D
      fluorescence spectra collected from aqueous POM extracts confirmed the evolution
      of organic matter from low-molecular reactive compounds to more complex and
      stable structures such as humic-like substances. FTIR confirmed the
      mineralization of POM's reactive constituents along the treatment chain by the
      decrease in the intensities of the characteristics bands of aliphatic compounds
      or proteins, and its humification in the sludge deposits through the relative
      increase of the bands at 1634cm-1 (vC=O) and 1238cm-1 (deltaC=O and/or deltaOH).
      Isotopic ratios delta2H/1H and delta15N/14N were found to be good indicators of
      POM evolutions. The higher values of delta2H/1H and delta15N/14N ratios measured
      in sludge deposits as compared to inflow suspended solids were related to POM
      humification and to microbial processes of POM hydrolysis and mineralization,
      respectively.

PMID- 29223908
TI  - The role of groundwater discharge fluxes on Si:P ratios in a major tributary to
      Lake Erie.
AB  - Groundwater discharge can be a major source of nutrients to river systems.
      Although quantification of groundwater nitrate loading to streams is common, the
      dependence of surface water silicon (Si) and phosphorus (P) concentrations on
      groundwater sources has rarely been determined. Additionally, the ability of
      groundwater discharge to drive surface water Si:P ratios has not been
      contextualized relative to riverine inputs or in-stream transformations. In this
      study, we quantify the seasonal dynamics of Si and P cycles in the Grand River
      (GR) watershed, the largest Canadian watershed draining into Lake Erie, to test
      our hypothesis that regions of Si-rich groundwater discharge increase surface
      water Si:P ratios. Historically, both the GR and Lake Erie have been considered
      stoichiometrically P-limited, where the molar Si:P ratio is greater than the
      ~16:1 phytoplankton uptake ratio. However, recent trends suggest that eastern
      Lake Erie may be approaching Si-limitation. We sampled groundwater and surface
      water for dissolved and reactive particulate Si as well as total dissolved P for
      12months within and downstream of a 50-km reach of high groundwater discharge.
      Our results indicate that groundwater Si:P ratios are lower than the
      corresponding surface water and that groundwater is a significant source of
      bioavailable P to surface water. Despite these observations, the watershed
      remains P-limited for the majority of the year, with localized periods of Si
      limitation. We further find that groundwater Si:P ratios are a relatively minor
      driver of surface water Si:P, but that the magnitude of Si and P loads from
      groundwater represent a large proportion of the overall fluxes to Lake Erie.

PMID- 29223909
TI  - Implications of alteration processes on radon emanation, radon production rate
      and W-Sn exploration in the Panasqueira ore district.
AB  - Alteration processes have strong impacts on the chemical and physical properties
      of rock masses. Because they can affect the contents and the distribution of U as
      well as enhance the permeability of the bedrock, they may lead to a significant
      increase of radon release to the environment. However, their influence on radon
      emanation and radon production rate has yet to be properly assessed. To
      investigate the impact of alteration processes on the radiological properties,
      samples were collected in the Panasqueira region under the influence of surface
      weathering, deuteric, hydrothermal and fault related alteration. Major and trace
      elements (U, Th), physical, and radiological properties were measured in
      metasedimentary and fault rocks. The degree of alteration and weathering progress
      were assessed through indices of alteration, porosity and bulk density. Overall,
      an increase of the radon emanation coefficient from (approximately) 0.1 to 0.4
      and radon production rate (from 40 to over 160Bq.m-3.h-1) is observed with the
      progress of physicochemical alteration. Decoupling of physical and chemical
      alteration however implies both must be quantified towards a proper assessment of
      the degree of alteration. The behavior of radiogenic elements upon alteration is
      shown to be complex and contingent upon the alteration process. An atypical
      increase of radon emanation in the ore district due to U mobilization was caused
      by hydrothermal alteration. Because radon emanation is not dependent upon the
      pelitic nature of the metasedimentary rocks, it may thus become a proxy for W-Sn
      exploration. The dependency of radon production rate from the latter constrains
      its use for exploration. Nevertheless, it may provide a reliable estimation of
      the bedrock contribution to indoor radon concentrations. Higher indoor radon
      concentrations, hence, a higher risk of exposure to radon are expected in the ore
      district as well as within fault zones.

PMID- 29223910
TI  - Analysis of the interactions between environmental and food contaminants, cadmium
      and deoxynivalenol, in different target organs.
AB  - Cadmium (Cd), a common and widespread toxic heavy metal, and mycotoxins such as
      deoxynivalenol (DON) are frequent contaminants of the food supply. Most of the
      data on their toxicity concern their effects when present alone. However,
      consumers can be exposed to a cocktail of DON and Cd. To improve the
      understanding of their combined toxicity, the effects of DON and Cd alone or in
      combination were investigated in different human cell lines from the kidney (HEK
      293), intestine (Caco-2), blood (HL-60) and liver (HepG2). Cytotoxicity was
      assessed through ATP measurement and types of interactions determined by the
      Isobologram-Combination index method. HEK-293 cells were exposed to increasing
      doses of DON, Cd and their combination at different ratios (DON/Cd of 2/1; 1/1;
      1/2 and 1/8). Regardless of the ratio, the type of interaction observed in HEK
      293 cells ranged from moderate antagonism to nearly additive with increasing
      cytotoxicity. In Caco-2 cells, the interactions ranged from nearly additive to
      antagonism whatever the ratio. At ratio 1/1, in HL-60 and HepG2 cells,
      interactions ranged from synergy to antagonism depending on the cytotoxicity
      level. Using human cells lines, this study indicates that the consequences of
      combined exposure to environmental and food contaminants are specific to the
      target organ. Further studies are needed to confirm these data in vivo.

PMID- 29223911
TI  - PCBs and PCDD/Fs in soil from informal e-waste recycling sites and open dumpsites
      in India: Levels, congener profiles and health risk assessment.
AB  - Growth of informal electronic waste (e-waste) recycling sector is an emerging
      problem for India. The presence of halogenated compounds in e-wastes may result
      in the formation of persistent organic pollutants like polychlorinated biphenyls
      (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during
      recycling processes. We therefore investigated PCBs and PCDD/Fs in surface soils
      explicitly from the informal e-waste recycling sites and nearby open dumpsites of
      major metropolitan cities from four corners of India, viz., New Delhi (North),
      Kolkata (East), Mumbai (West) and Chennai (South). In the informal e-waste
      recycling sites, the range of Sigma26PCBs (0.4-488ng/g) and ?PCDD/Fs (1.0
      10.6ng/g) were higher than ?26PCBs (0.3-21ng/g) and ?PCDD/Fs (0.15-7.3ng/g) from
      open dumpsites. In the e-waste sites, ?PCDDs were found with increasing trend
      from ?TetraCDD to OctaCDD, whereas ?PCDFs showed a reverse trend. The dominance
      of PCDF congeners and maximum toxicity equivalents (TEQ) for both PCDDs (17pg
      TEQ/g) and PCDFs (82pg TEQ/g) at Mandoli in New Delhi has been related to
      intensive precious metal recovery process using acid bath. Among dumpsites,
      highest TEQ for PCDD/Fs was observed at Kodangaiyur dumpsite of Chennai (CNDS-02,
      45pg TEQ/g). Positive Matrix Factorization (PMF) model identified distinct
      congener pattern based on the functional activities, such as e-waste dismantling,
      shredding, precious metal recovery and open burning in dumpsites. E-waste metal
      recovery factor was loaded with 86-91% of PCB-77, -105, -114, -118 and 30% of PCB
      126, possibly associated with the burning of wires during the copper extraction
      process. Almost 70% of the ?26PCB concentrations was comprised of the dioxin-like
      PCB congeners with a maximum concentration of 437ng/g at New Moore market in
      Chennai, followed by Wire Lane (102ng/g), in Mumbai. We speculate that PCB-126
      might have resulted from combustion of plastic materials in e-waste stream and
      dumped waste.

PMID- 29223912
TI  - Prenatal buprenorphine exposure and neonatal neurobehavioral functioning.
AB  - AIMS: Assessments of effects of prenatal opioid exposure on the neonate have
      consisted principally of evaluations of neonatal abstinence syndrome (NAS) to
      determine the need for pharmacotherapy. The purpose of this study was to
      comprehensively evaluate the effects of gestational maternal buprenorphine
      maintenance on newborn neurobehavioral functioning. STUDY DESIGN: Maternal
      substance use history and psychosocial demographics that can contribute to the
      neurobehavioral functioning of the infant were explored. Infants were assessed
      using the NICU Network Neurobehavioral Scale (NNNS) to measure their neurologic
      and behavioral functioning and signs of stress/abstinence on days 3, 14 and 30 of
      life. SUBJECTS: Participants were 41 pregnant buprenorphine-maintained women and
      their infants. RESULTS: Maternal buprenorphine dose at delivery was negatively
      correlated with infant quality of movement and self-regulation, and positively
      correlated with the central nervous system parameters of stress/abstinence at day
      3 of life. As maternal buprenorphine dose increased, the mean morphine dose that
      the infant required for NAS treatment significantly increased. No differences
      were found when comparing the NNNS domain scores between infants who required
      pharmacotherapy for NAS versus those who did not at day 3 of life. CONCLUSIONS:
      Buprenorphine exposure during pregnancy can alter neonatal neurobehavioral and
      physiological responses to stimuli. A systematic evaluation of the newborn's
      functional domains above NAS assessment alone is crucial to address the
      challenges created by neurobehavioral dysregulation associated with substance
      exposure, improve caregiver/infant interaction and developmental trajectory.
      Comprehensive pre/postnatal treatment of buprenorphine-maintained mothers can
      lead to healthier outcomes for the dyad.

PMID- 29223913
TI  - Prevalence of childhood trauma and correlations between childhood trauma,
      suicidal ideation, and social support in patients with depression, bipolar
      disorder, and schizophrenia in southern China.
AB  - BACKGROUND: Childhood trauma has long-term adverse effects on physical and
      psychological health. Previous studies demonstrated that suicide and mental
      disorders were related to childhood trauma. In China, there is insufficient
      research available on childhood trauma in patients with mental disorders.
      METHODS: Outpatients were recruited from a psychiatric hospital in southern
      China, and controls were recruited from local communities. The demographic
      questionnaire, the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the
      Social Support Rating Scale (SSRS) were completed by all participants, and the
      Self-rating Idea of Suicide Scale (SIOSS) were completed only by patients.
      Prevalence rates of childhood trauma were calculated. Kruskal-Wallis test and
      Dunnett test were used to compare CTQ-SF and SSRS scores between groups. Logistic
      regression was used to control demographic characteristics and examine
      relationships between diagnosis and CTQ-SF and SSRS scores. Spearman's rank
      correlation test was conducted to analyze relationships between suicidal ideation
      and childhood trauma and suicidal ideation and social support. RESULTS: The final
      sample comprised 229 patients with depression, 102 patients with bipolar, 216
      patient with schizophrenia, and 132 healthy controls. In our sample, 55.5% of the
      patients with depression, 61.8% of the patients with bipolar disorder, 47.2% of
      the patients with schizophrenia, and 20.5% of the healthy people reported at
      least one type of trauma. In patient groups, physical neglect (PN) and emotional
      neglect (EN) were most reported, and sexual abuse (SA) and physical abuse (PA)
      were least reported. CTQ-SF and SSRS total scores, and most of their subscale
      scores in patient groups were significantly different from the control group.
      After controlling demographic characteristics, mental disorders were associated
      with higher CTQ-SF scores and lower SSRS scores. CTQ-SF scores and number of
      trauma types were positively correlated with the SIOSS score. Negative
      correlations existed between SSRS scores and the SIOSS score. LIMITATIONS: Our
      sample may not be sufficiently representative. Some results might have been
      interfered by demographic characteristics. The SIOSS was not completed by
      controls. Data from self-report scales were not sufficiently objective.
      CONCLUSIONS: In southern China, childhood trauma is more severe and more
      prevalent in patients with mental disorders (depression, bipolar disorder and
      schizophrenia) than healthy people. Among patients with mental disorders in
      southern China, suicidal ideation is associated with childhood trauma and poor
      social support.

PMID- 29223915
TI  - Marijuana buyers in the United States, 2010-2014.
AB  - BACKGROUND: Obtaining or purchasing marijuana in the U.S. can be done only in
      certain states via a lawful market for medical or non-medical (recreational)
      purposes, or via an unlawful market ("black market") by home cultivation and
      unlicensed vendors and individuals. Given the evolving U.S. state marijuana
      legislation landscape, the objective of this study is to describe individuals who
      report buying marijuana in the past year by selected characteristics and U.S.
      geographical location. METHODS: Using data from the 2010-2014 National Survey on
      Drug Use and Health (NSDUH), we conducted bivariate chi-square tests to examine
      sociodemographic and selected behavioral indicators associated with buying
      marijuana and analyzed these factors in a multivariable logistic regression
      model. NSDUH participants were the noninstitutionalized civilian population aged
      12+ (approximately 62,100 individuals per year) who reported using marijuana in
      the past year (approximately 12,400 annual average). RESULTS: A weighted estimate
      of approximately 18.5 million individuals aged 12+ reported buying marijuana in
      the past year (59% of marijuana users). Overall, buyers of marijuana were more
      likely to be male, report using marijuana for a greater number of days, and to
      meet the criteria for substance use disorder and marijuana dependence. Data
      showed differences of proportion of marijuana buyers by state of residence.
      CONCLUSIONS: Given recent changes in state laws and policies and the increased
      demand for marijuana products, continued monitoring of the U.S. marijuana market
      in coming years is important in order to understand consumption and buying
      patterns among at-risk segments of the population, especially youth.

PMID- 29223914
TI  - Cannabis use disorder and male sex predict medical cannabis card status in a
      sample of high risk adolescents.
AB  - OBJECTIVE: To examine if a substance use disorder (SUD), especially cannabis use
      disorder in adolescence, predicts future medical cannabis card status among high
      risk youth. METHODS: Data collection occurred in Denver and San Diego. We
      recruited adolescents, with or at high risk for SUD and conduct problems
      (hereafter probands) and their siblings (n=654). Baseline (Wave 1) assessments
      took place between 1999 and 2008, and follow-up (Wave 2) took place between 2010
      and 2013. In initial bivariate analyses, we examined whether baseline DSM-IV
      cannabis abuse/dependence (along with other potential predictors) was associated
      with possessing a medical cannabis card in young adulthood (Wave 2). Significant
      predictors were then included in a multiple binomial regression. Self-reported
      general physical health was also evaluated at both time points. Finally, within
      Wave 2, we tested whether card status was associated with concurrent substance
      dependence. RESULTS: About 16% of the sample self-reported having a medical
      cannabis card at follow-up. Though bivariate analyses demonstrated that multiple
      predictors were significantly associated with Wave 2 card status, in our multiple
      binomial regression only cannabis abuse/dependence and male sex remained
      significant. At Wave 2, those with a medical cannabis card were significantly
      more likely to endorse criteria for concurrent cannabis dependence. There was no
      significant difference in self-reported general physical health. CONCLUSIONS:
      Cannabis abuse/dependence and male sex positively predicted future medical
      cannabis card holder status among a sample of high risk adolescents. Physicians
      conducting evaluations for medical cannabis cards should carefully evaluate and
      consider past and concurrent cannabis addiction.

PMID- 29223917
TI  - Molecular dynamics simulations suggest changes in electrostatic interactions as a
      potential mechanism through which serine phosphorylation inhibits DNA Polymerase
      beta's activity.
AB  - DNA polymerase beta is a 39kDa enzyme that is a major component of Base Excision
      Repair in human cells. The enzyme comprises two major domains, a 31kDa domain
      responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and
      has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase beta was shown
      to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55
      (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its
      ability to bind ssDNA. In this study, we investigate the potential
      phosphorylation-induced structural changes for DNA polymerase beta using
      molecular dynamics. The simulations show drastic conformational changes of the
      polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced
      conformational changes transform the closed (active) enzyme structure into an
      open one. Further analysis of the results points to a key hydrogen bond and newly
      formed salt bridges as potential drivers of these structural fluctuations. The
      changes observed with S44/55 and S55 phosphorylation were less dramatic than S44
      and the integrity of the H-bond was not compromised. Thus the phosphorylation of
      S44 is likely the major contributor to structural fluctuations that lead to loss
      of enzymatic activity.

PMID- 29223916
TI  - Performance of cigarette susceptibility index among e-cigarette and hookah users.
AB  - OBJECTIVE: Susceptibility to cigarette smoking has been used since the mid-1990s
      as a measure to identify youth at risk of cigarette initiation. However, it is
      unclear how well this measure predicts future smoking among electronic (e
      )cigarette or hookah users, or among those in tobacco-friendly social
      environments. METHODS: We used prospective data from the Southern California
      Children's Health Study to evaluate the performance (sensitivity, specificity,
      predictive value) of a composite index assessing susceptibility to smoking, and
      to evaluate whether performance of the measure differed by use of e-cigarettes or
      hookah, or immersion in a tobacco-friendly social environment. Susceptibility to
      cigarette smoking was measured in 11th/12th grade (2014) among never cigarette
      smokers (N=1266); follow-up data on smoking initiation were obtained
      approximately 16 months later. RESULTS: Overall, 16.4% of youth initiated smoking
      between baseline and follow-up. The sensitivity of the susceptibility to smoking
      index was low (46.4%), and specificity was high (79.0%). No difference in
      sensitivity was observed by baseline e-cigarette use; specificity was higher
      among never e- cigarette users. Differences in negative predictive value (NPV)
      and positive predictive value (PPV) were also observed by baseline e-cigarette
      and hookah use. Specificity was generally lower, and sensitivity was generally
      higher for those in tobacco-friendly social environments. CONCLUSIONS: Our
      findings suggest that use of the susceptibility to smoking index in cross
      sectional studies of older adolescents to identify those likely to begin smoking
      may be inappropriate for those using alternative tobacco products (e.g., e
      cigarettes or hookah).

PMID- 29223918
TI  - Postmortem computed tomography findings in cases of bath-related death:
      Applicability and limitation in forensic practice.
AB  - PURPOSE: Bath-related deaths occur frequently in Japan, and many of these deaths
      are diagnosed as death from disease without autopsy in the current Japanese death
      investigation system. Therefore, we aimed to examine the postmortem computed
      tomography (PMCT) findings of bath-related deaths to determine if PMCT can
      differentiate between real cases of drowning and sudden deaths not related to
      drowning. METHODS: Bath-related deaths were sampled from all autopsies conducted
      at the Tokyo Medical Examiner's Office from September 2015 to August 2016. A
      total of 90 bath-related deaths (77 drowning cases and 13 non-drowning cases) and
      50 controls (sudden cardiac deaths non-related to bathing) were included in this
      study. We investigated factors contributing to drowning and measured PMCT
      parameters (presence/density of fluid in the maxillary sinus/trachea, distance
      between the lungs, lung patterns [ground glass opacities, consolidation],
      position of the right diaphragmatic dome, density in the right atrium, stomach
      volume, and density of the gastric/duodenal contents). RESULTS: The analysis of
      the factors contributing to drowning showed that alcohol intoxication was the
      most frequent (n=25), followed by cardiac pathology (n=22), and psychotropic drug
      intoxication (n=6). Radiological evaluation showed that measurements of all
      parameters differed significantly between the drowning group and the controls. In
      addition, significant differences were observed between drowning and non-drowning
      cases in three radiological parameters (i.e., distance between lungs, stomach
      volume, and density of gastric contents). CONCLUSIONS: Majority of bath-related
      deaths in this study showed signs of drowning at autopsy, and we observed a range
      of factors that contributed to drowning. By using several radiological parameters
      (e.g., the distance between the lungs, stomach volume, and the density of the
      gastric contents), PMCT for the investigation of bath-related deaths might
      indicate that drowning as opposed to other factors unrelated to drowning (e.g.,
      sudden cardiac death) was the cause of death. This might allow for calculation of
      accurate mortality statistics on bath-related deaths.

PMID- 29223920
TI  - Streptococcus agalactiae bacteremia in non-pregnant adult patients at two
      teaching hospitals.
AB  - Streptococcus agalactiae or group B streptococcus (GBS) is a frequent pathogen in
      immunocompromised adults. The aim of this study was to determine the relative
      frequency, clinical presentation, antimicrobial susceptibility profile, and risk
      factors associated with GBS bacteremia in non-pregnant adult patients. We
      conducted a retrospective analysis of blood cultures performed in two hospitals
      between the years 2009-2013. From 1110 bacteremia episodes, 13 were caused by
      GBS, all of which were susceptible to ampicillin. GBS bacteremia was more
      frequent in females and in patients older than 60 years of age. The most frequent
      comorbidities were chronic kidney disease, cardiac failure and neoplasia. History
      of appendectomy was detected in 53.8% of the patients, being the most relevant
      comorbidity for GBS bacteremia in the multivariate analysis (OR 4.13, p=0.012).
      The main presentations were primary bacteremia and soft tissue infection. GBS
      bacteremia was infrequent in our institution, and a history of appendectomy might
      be related to bacteremia occurrence.

PMID- 29223919
TI  - [Temporal diversity dynamics of the arbuscular mycorrhizal fungi of Larrea
      tridentata (Sesse & Mocino ex DC) Coville in a semi-arid ecosystem].
AB  - Arbuscular mycorrhizal fungi (AMF) of arid and semiarid ecosystems are important
      for the development of plants that grow under biotic stress in wild or in agro
      ecosystems. There is little information on the temporal diversity of these
      organisms in perennial plants from arid ecosystems in northern Mexico. On this
      study, the mycorrhizal colonization and the temporal diversity of AMF in the
      rhizosphere of Larrea tridentata, perennial plant abundant in the Chihuahuan
      Desert region were explored. Samples of the rhizosphere and roots of fifteen
      plants in each of the three sampling dates during the 2015 year were obtained. A
      total of 17 species of HMA belonging to 12 genera and 7 families within the
      phylum Glomeromycota in all three sampling dates were found. Funneliformis
      geosporum was the dominant species belonging to the family Glomeraceae which
      possess the highest genera number on L. tridentata. The highest mycorrhization
      percentage was in February with 83.22, followed by September and May with 75.27
      and 65.27%, respectively. A maximum of 16 AM fungal species were isolated and
      identified from L. tridentata rhizosphere in February, 15 species in May and 12
      species in September. Statistical analysis showed significant differences between
      sampling dates in the spores number.

PMID- 29223921
TI  - Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats:
      Thiol conjugation as a potential metabolic pathway.
AB  - Alantolactone (AL) and isoalantolactone (IAL), two major active sesquiterpene
      lactones isolated from Radix Inulae extract, have a wide range of pharmacological
      activities. The predominant metabolic pathway of AL and IAL observed was
      glutathione (GSH) conjugation in vitro, which could occur in the absence of
      metabolic enzymes. Non-enzymatic conjugation with cysteine (Cys) couldalso be
      observed. Four metabolites (AL-GSH, AL-Cys, IAL-GSH, IAL-Cys) were subsequently
      isolated and confirmed by nuclear magnetic resonance (NMR). The results indicated
      that the thiol of GSH or Cys can be reacted with the exomethylene carbon atoms of
      alpha, beta-unsaturated carbonyl of AL and IAL. After intravenous administration
      in rats, AL and IAL were extensively metabolized, and the exposure, as measured
      by area under the concentration-time curve (AUC), for AL-GSH, AL-Cys, IAL-GSH,
      and IAL-Cys was approximately 1.54-, 0.96-, 1.50-, and 0.91-fold that of the
      parent drug, respectively. The AUC ratio of metabolites to parent compounds of
      oral administration was 3.66-, 9.19-, 12.97-, and 9.92-fold that of the parent
      drug for the above metabolites, respectively. The bioavailability of AL-total
      (AL, AL-GSH, AL-Cys) and IAL-total (IAL, IAL-GSH, IAL-Cys) was, respectively,
      8.39% and 13.07%, which was 3.62- and 6.95- fold that of AL (2.32%) and IAL
      (1.88%), respectively. The oral exposure will be underestimated if the parent
      drugs are tested alone. These findings provide useful information for preclinical
      safety evaluation, and for predicting AL and IAL metabolism in humans.

PMID- 29223922
TI  - Iso/Anisohydry: A Plant-Environment Interaction Rather Than a Simple Hydraulic
      Trait.
AB  - Plants are frequently classified as isohydric or anisohydric in an attempt to
      portray their water relations strategy or ecological niche. However, despite the
      popularity of the iso/anisohydric classification, the underlying biology remains
      unclear. We use here a simple hydraulic model and the extensive literature on
      grapevine hydraulics to illustrate that the iso/anisohydric classification of a
      plant depends on the definition used and the environment in which it is grown,
      rather than describing an intrinsic property of the plant itself. We argue that
      abandoning the iso/anisohydric terminology and returning to a more fundamental
      hydraulic framework would provide a stronger foundation for species comparisons
      and ecological predictions.

PMID- 29223923
TI  - Plant Defenses against Herbivory: Closing the Fitness Gap.
AB  - Many morphological and chemical features of plants are classified as plant
      defenses against herbivores. By definition, plant defenses should increase a
      plant's fitness (i.e., its contribution to the gene pool of the next generation)
      as a function of herbivory. Over the past years, substantial progress has been
      made in understanding and manipulating the mechanistic basis of many putative
      plant defense traits. However, most plant defenses are still characterized by
      proximate variables such as herbivore performance or plant damage rather than
      actual fitness. Determining fitness benefits as a function of herbivory therefore
      remains a major knowledge gap that must be filled to understand the ecology and
      evolution of plant defenses.

PMID- 29223924
TI  - UTR-Dependent Control of Gene Expression in Plants.
AB  - Throughout their lives, plants sense many developmental and environmental
      stimuli, and activation of optimal responses against these stimuli requires
      extensive transcriptional reprogramming. To facilitate this activation, plant
      mRNA contains untranslated regions (UTRs) that significantly increase the coding
      capacity of the genome by producing multiple mRNA variants from the same gene. In
      this review we compare UTRs of arabidopsis (Arabidopsis thaliana) and rice (Oryza
      sativum) at the genome scale to highlight their complexity in crop plants. We
      discuss different modes of UTR-based regulation with emphasis on genes that
      regulate multiple plant processes, including flowering, stress responses, and
      nutrient homeostasis. We demonstrate functional specificity in genes with
      variable UTR length and propose future research directions.

PMID- 29223925
TI  - Characterizing interaction forces between actin and proteins of the tropomodulin
      family reveals the presence of the N-terminal actin-binding site in leiomodin.
AB  - Tropomodulin family of proteins includes several isoforms of tropomodulins (Tmod)
      and leiomodins (Lmod). These proteins can sequester actin monomers or nucleate
      actin polymerization. Although it is known that their actin-binding properties
      are isoform-dependent, knowledge on how they vary in strengths of interactions
      with G-actin is missing. While it is confirmed in many studies that Tmods have
      two actin-binding sites, information on number and location of actin-binding
      sites in Lmod2 is controversial. We used atomic force microscopy to study
      interactions between G-actin and proteins of the tropomodulin family. Unbinding
      forces between G-actin and Tmod1, Tmod2, Tmod3, or Lmod2 were quantified. Our
      results indicated that Tmod1 and Tmod3 had unimodal force distributions, Tmod2
      had a bimodal distribution and Lmod2 had a trimodal distribution. The number of
      force distributions correlates with the proteins' abilities to sequester actin or
      to nucleate actin polymerization. We assigned specific unbinding forces to the
      individual actin-binding sites of Tmod2 and Lmod2 using mutations that destroy
      actin-binding sites of Tmod2 and truncated Lmod2. Our results confirm the
      existence of the N-terminal actin-binding site in Lmod2. Altogether, our data
      demonstrate how the differences between the number and the strength of actin
      binding sites of Tmod or Lmod translate to their functional abilities.

PMID- 29223927
TI  - Biochemical characterization of the YBPCI miniprotein, the first carboxypeptidase
      inhibitor isolated from Yellow Bell Pepper (Capsicum annuum L). A novel
      contribution to the knowledge of miniproteins stability.
AB  - The cystine-knot metallocarboxypeptidase inhibitors (MCPIs) are peptides that
      contribute to control proteolytic activity, involved in storage, growth and
      maintenance of plants. Lately studies reported several MCPIs with potential use
      in biomedical applications; as anti-cancer, anti-thrombotic, anti-malaric and
      anti-angiogenic agents. We report the isolation, purification, chemical stability
      and biochemical characterization of a novel carboxypeptidase A inhibitor (YBPCI)
      isolated from Capsicum annuum L. var. Yellow Bell Pepper, the first cystine-knot
      miniprotein (CKM) of the species. We demonstrate the stability of YBPCI (IC50 =
      0.90 MUg/ml) to high temperatures, high salt concentration and extreme pH values.
      MALDI-TOF/MS analysis detected a molecular weight of 4057 Da, and peptide mass
      fingerprint resulted in no matches with other protease inhibitors. In vitro
      gastrointestinal digestion subjecting YBPCI to pH 2 incubation and proteolytic
      attack resulted in complete inhibitory activity. To summarize, there are no
      reports to date of carboxypeptidase inhibitors in C. annuum species, giving our
      report much more relevance.

PMID- 29223928
TI  - Are there risk factors for false-positive malformation diagnoses on obstetric
      ultrasound? A nested case-control study.
AB  - INTRODUCTION: In a population-based study, we found an overall false-positive
      rate of 8.8% for the second and third trimester ultrasounds. Although numerous
      studies have been performed to examine factors which lead to false negatives, the
      same is not true for the factors associated with false positives. The principal
      objective of this study was to look for risk factors for false-positive diagnoses
      of fetal malformations on obstetric ultrasound scans. MATERIAL AND METHODS: In
      this nested case-control study, the case infants were those whose mother had a
      false-positive antenatal ultrasound diagnosis of a malformation during the second
      or third trimester (ultrasound false-positives) and who were live - or stillborn
      in Auvergne in 2006-2010. The control group comprised all children who were
      ultrasound true-negatives in 2005 and 2007. The study included 46 cases and 184
      controls, matched according to the level of the maternity unit in which they were
      born. RESULTS: Most false-positive diagnoses were minor malformations. The mean
      term at this false-positive diagnosis was 27.7+/-5.4 weeks; in 46.8% of cases,
      the diagnosis was made during the second-trimester ultrasound. A single
      malformation was suspected in 95.7% of the cases. In 97.9% of cases, only one
      anatomical system was affected. In all, 49 malformations were identified among
      the 46 cases and their distribution differed according to anatomical system. The
      only risk factor identified was a body mass index (BMI)<25 (ORa=1.7; 95%CI: 1.2
      2.4). DISCUSSION: A maternal BMI<25 was the only risk factor identified for a
      false-positive ultrasound diagnosis of a fetal malformation.

PMID- 29223926
TI  - An update on factor XI structure and function.
AB  - Factor XI (FXI) is the zymogen of a plasma protease, factor XIa (FXIa), that
      contributes to thrombin generation during blood coagulation by proteolytic
      activation of several coagulation factors, most notably factor IX (FIX). FXI is a
      homolog of prekallikrein (PK), a component of the plasma kallikrein-kinin system.
      While sharing structural and functional features with PK, FXI has undergone
      adaptive changes that allow it to contribute to blood coagulation. Here we review
      current understanding of the biology and enzymology of FXI, with an emphasis on
      structural features of the protein as they relate to protease function.

PMID- 29223929
TI  - The minimum monitoring signal-to-noise ratio for off-axis signals and its
      implications for directional hearing aids.
AB  - The signal-to-noise ratio (SNR) benefit of hearing aid directional microphones is
      dependent on the angle of the listener relative to the target, something that can
      change drastically and dynamically in a typical group conversation. When a new
      target signal is significantly off-axis, directional microphones lead to slower
      target orientation, more complex movements, and more reversals. This raises the
      question of whether there is an optimal design for directional microphones. In
      principle an ideal microphone would provide the user with sufficient
      directionality to help with speech understanding, but not attenuate off-axis
      signals so strongly that orienting to new signals was difficult or impossible. We
      investigated the latter part of this question. In order to measure the minimal
      monitoring SNR for reliable orientation to off-axis signals, we measured head
      orienting behaviour towards targets of varying SNRs and locations for listeners
      with mild to moderate bilateral symmetrical hearing loss. Listeners were required
      to turn and face a female talker in background noise and movements were tracked
      using a head-mounted crown and infrared system that recorded yaw in a ring of
      loudspeakers. The target appeared randomly at +/- 45, 90 or 135 degrees  from the
      start point. The results showed that as the target SNR decreased from 0 dB to -18
      dB, first movement duration and initial misorientation count increased, then
      fixation error, and finally reversals increased. Increasing the target angle
      increased movement duration at all SNRs, decreased reversals (above -12 dB target
      SNR), and had little to no effect on initial misorientations. These results
      suggest that listeners experience some difficulty orienting towards sources as
      the target SNR drops below -6 dB, and that if one intends to make a directional
      microphone that is usable in a moving conversation, then off-axis attenuation
      should be no more than 12 dB.

PMID- 29223930
TI  - Frequency selectivity in macaque monkeys measured using a notched-noise method.
AB  - The auditory system is thought to process complex sounds through overlapping
      bandpass filters. Frequency selectivity as estimated by auditory filters has been
      well quantified in humans and other mammalian species using behavioral and
      physiological methodologies, but little work has been done to examine frequency
      selectivity in nonhuman primates. In particular, knowledge of macaque frequency
      selectivity would help address the recent controversy over the sharpness of
      cochlear tuning in humans relative to other animal species. The purpose of our
      study was to investigate the frequency selectivity of macaque monkeys using a
      notched-noise paradigm. Four macaques were trained to detect tones in noises that
      were spectrally notched symmetrically and asymmetrically around the tone
      frequency. Masked tone thresholds decreased with increasing notch width. Auditory
      filter shapes were estimated using a rounded exponential function. Macaque
      auditory filters were symmetric at low noise levels and broader and more
      asymmetric at higher noise levels with broader low-frequency and steeper high
      frequency tails. Macaque filter bandwidths (BW3dB) increased with increasing
      center frequency, similar to humans and other species. Estimates of equivalent
      rectangular bandwidth (ERB) and filter quality factor (QERB) suggest macaque
      filters are broader than human filters. These data shed further light on
      frequency selectivity across species and serve as a baseline for studies of
      neuronal frequency selectivity and frequency selectivity in subjects with hearing
      loss.

PMID- 29223931
TI  - Prevalence of anxiety disorders in epilepsy.
AB  - OBJECTIVE: Anxiety disorders (ADs) are common in patients with epilepsy (PWE).
      The aim of this study was to estimate the prevalence of specific ADs in
      outpatients with epilepsy. METHODS: A group of 118 consecutive outpatients with
      epilepsy were screened, and 96 patients meeting inclusion criteria were examined
      by a trained psychiatrist using Structured Clinical Interview (SICD-I) for
      Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text
      Revision) (DSM-IV-TR). RESULTS: A diagnosis of any current AD was established in
      16 (16.7%) out of 96 participants. Furthermore, panic disorder (PD) was the most
      frequent AD; it was observed in 13.5% of PWE and constituted 81.2% of the
      identified ADs in the study group. Older age and later age of seizure onset were
      associated with increased odds of AD diagnosis. STUDY LIMITATIONS: The cross
      sectional study design, a consecutive sample of patients presenting to a tertiary
      referral center, and small sample size of the population could have affected the
      results. CONCLUSIONS: Panic disorder and other forms of AD are common among PWE.
      Age and age of seizure onset are important factors associated with AD among PWE.

PMID- 29223932
TI  - Pregnancy-related knowledge of women with epilepsy - An internet-based survey in
      German-speaking countries.
AB  - There are several issues, which have to be acknowledged, when treating women with
      epilepsy (WWE). The need for counseling WWE in Germany with epilepsy on pregnancy
      related matters was stressed in several papers and medical guidelines. Physicians
      treating WWE in Germany therefore should be aware of the information needs of
      their patients. We aimed to determine the level of pregnancy-related knowledge of
      WWE and their informational needs concerning pregnancy and childbirth issues in
      German-speaking countries by an internet-based survey. The questionnaire
      consisted of 18 questions addressing the characteristics of the epilepsy
      syndromes, the patients' experience with pregnancy, and the sources of their
      pregnancy-related knowledge. Another 20 items addressed the level of pregnancy
      related knowledge. One hundred ninety-two women (179 patients, 13 relatives; age:
      30.5+/-10.8years) participated. Most of the women got information and advice on
      the treatment of epilepsy from a neurologist (81%). Most of the women had
      obtained information concerning driving license (72%) followed by information
      about pregnancy and delivery (60%). The women, who remembered being counseled
      about pregnancy-related matters gave more correct answers to the pregnancy
      related questions than the others (51+/-17% vs. 38+/-24%, p<0.011). Thirty-eight
      percent of WWE taking enzyme inducing antiepileptic drugs (AEDs) were unaware of
      the interaction with oral contraception. Forty-one percent of WWE taking
      valproate were unaware of its high teratogenicity, and 89% of WWE had not been
      counseled about potentially reduced bone mineral density. Forty-six percent of
      participants did not believe that the majority of WWE have healthy children. The
      findings of this survey reveal considerable information needs of WWE concerning
      pregnancy-related matters in German-speaking countries.

PMID- 29223933
TI  - Task-based and resting-state fMRI reveal compensatory network changes following
      damage to left inferior frontal gyrus.
AB  - Damage to left inferior prefrontal cortex in stroke aphasia is associated with
      semantic deficits reflecting poor control over conceptual retrieval, as opposed
      to loss of knowledge. However, little is known about how functional recruitment
      within the semantic network changes in patients with executive-semantic deficits.
      The current study acquired functional magnetic resonance imaging (fMRI) data from
      14 patients with semantic aphasia, who had difficulty with flexible semantic
      retrieval following left prefrontal damage, and 16 healthy age-matched controls,
      allowing us to examine activation and connectivity in the semantic network. We
      examined neural activity while participants listened to spoken sentences that
      varied in their levels of lexical ambiguity and during rest. We found group
      differences in two regions thought to be good candidates for functional
      compensation: ventral anterior temporal lobe (vATL), which is strongly implicated
      in comprehension, and posterior middle temporal gyrus (pMTG), which is
      hypothesized to work together with left inferior prefrontal cortex to support
      controlled aspects of semantic retrieval. The patients recruited both of these
      sites more than controls in response to meaningful sentences. Subsequent analysis
      identified that, in control participants, the recruitment of pMTG to ambiguous
      sentences was inversely related to functional coupling between pMTG and anterior
      superior temporal gyrus (aSTG) at rest, while the patients showed the opposite
      pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was
      associated with better performance on a test of verbal semantic association,
      suggesting that this temporal lobe connection supports comprehension in the face
      of damage to left inferior prefrontal cortex. These results characterize network
      changes in patients with executive-semantic deficits and converge with studies of
      healthy participants in providing evidence for a distributed system underpinning
      semantic control that includes pMTG in addition to left inferior prefrontal
      cortex.

PMID- 29223934
TI  - [Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin
      therapy. Results of the global HAT study in Argentina].
AB  - We describe the results of the HAT study in 433 Argentinean patients with type 1
      diabetes (T1D) and 823 with type 2 diabetes (T2D). HAT was an international non
      interventional study assessing severe and non-severe hypoglycaemia in patients
      with T1D and T2D under insulin treatment through a two-part self-assessment
      questionnaire (retrospective and prospective). The annual incidence of at least
      one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D
      (retrospective), 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively
      (prospective). Hypoglycaemia affected quality of life (on a scale of 0-10 for
      fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10), daily life,
      occupational or academic performance (2.1% with T1D and 3.2% with T2D did not
      attend to their work after hypoglycaemia), and induced an increased use of health
      resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51%
      consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9%
      exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6%
      food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended
      exercises). Greater numbers of episodes were recorded in the prospective period.
      An instrument to assess hypoglycaemia in clinical practice and strategies to
      reduce their risk are required. It is also important to ask about the episodes
      and reinforce the education of patients and close relatives on hypoglycaemia
      prevention and treatment.

PMID- 29223935
TI  - [Iron intake and HFE gen in male adults from Buenos Aires].
AB  - Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene
      may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors
      (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI),
      hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA
      Computer Program and Food Composition Table, USDA). Serum ferritin and
      transferrin saturation were determined; criteria for Fe overload was serum
      ferritin > 300 ng/ml and transferrin saturation = 50%. HFE genotypes C282Y, H63D
      and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI
      lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the
      upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and
      47.7% of daily Fe intake, respectively. A significant association was observed
      between the increase in serum ferritin (ng/ml) and the increase in FeI (p =
      0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin
      saturation = 50%. Genotypes associated with hereditary hemochromatosis (H63D,
      S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin
      saturation was higher in subjects carrying mutation than in wild type subjects (p
      = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group
      was only 1.2%, an excessive Fe intake could enhance adverse effects in
      individuals unaware of any family history of Fe overload.

PMID- 29223936
TI  - [Relationship between crowding and community acquired skin and soft tissues
      infections].
AB  - The association of the spread of community infections with poverty and
      overcrowding is well known. In our hospital, located in Jose C. Paz, we assist
      sporadic cases of post-cesarean infections caused by community acquired
      methicillin-resistant Staphylococcus aureus (CaMRSA). In a prospective study of
      families treated at our hospital, we investigated the relationship between a
      history of skin and soft tissue infections (SSTI) and extreme overcrowding
      defined as households with unsatisfied basic needs type 3 (NBI 3). A total of 264
      households were included in the study; 109 (41.3%) had a history of SSTI and 59
      (22.3%) were NBI 3. A total of 61.0% of the NBI 3 households and 35.6% of the non
      NBI 3 households reported SSTI (p = 0.00047). Using Google Maps, we georeferenced
      households and identified them on a NBI map adapted from the 2010 demographic
      census. In neighborhoods with NBI > 9.7%, 51.2% of the households had a history
      of SSTI. When NBI was < 9.7%, the percentage fell to 31.1% (p = 0.0019). These
      results are suggestive of an association of SSTI acquired in the community with
      overcrowding and poverty. The presence of CaMRSA in community SSTIs should be
      suspected. Vancomycin or clindamycin prophylaxis could be considered when
      cesarean deliveries are performed in women from areas with high NBI or with a
      history of SSTI.

PMID- 29223937
TI  - Echinococcosis and other parasitic infections in domestic dogs from urban areas
      of an Argentinean Patagonian city.
AB  - In urban populations of South America, dogs with free access to public areas
      represent a public health concern. The primary consequence of roaming dogs on
      human health is the transmission of infectious and parasitic diseases mainly
      through feces contamination. The main diseases likely to be transmitted are
      hydatidosis or echinococcosis, larva migrans, and giardiasis. In Argentina,
      hydatidosis ranks among the most prevalent zoonosis. Although it is considered a
      rural disease, the circulation of this parasite in urban areas has been
      documented. The aim of this work was to survey intestinal parasites in canine
      feces from two low-income urban neighborhoods of Bariloche city, Argentina, and
      to assess their seasonal variation. During 2016, 188 fresh dog feces were
      collected from sidewalks in 40 randomly selected blocks from the neighborhoods.
      Each sample was processed by Sheater flotation and tested for a coproantigen
      (CAg) by ELISA. The percentage of parasitized feces was 65.3% (95% CI: 55.9%
      73.8%). Eleven parasite species were found, 3 protozoan, 3 cestodes, and 5
      nematodes. Echinococcus sp. was present in 9.3% of the samples (95% CI: 4.7%
      16.1%). Canine echinococcosis rates resulted similar to rates found previously in
      other neighborhoods of the city. The life cycle of Echinococcus sp. is sustained
      in urban areas by the entry of parasitized livestock, domiciliary slaughtering,
      and inadequate deposition of offal. The risk of Echinococcus sp. transmission to
      people in these neighborhoods is very high, due to high density of free-roaming
      dogs and high percentages of infected feces, similar to percentages observed in
      rural areas.

PMID- 29223938
TI  - [Prevalence of anti-Toxoplasma gondii antibodies in blood donors in Buenos Aires
      city, from 1967 to 2017].
AB  - A prevalence study of antibodies anti Toxoplasma gondii in voluntary blood donors
      who attended the hemotherapy service at the Hospital Aleman during the first four
      months of the years 1997, 2007 and 2017 was carried out and the results were
      compared to the study carried out in 1967. The sera where processed with the
      Sabin Feldman Dye Test. The global average seroprevalence in 1967 was 67.0%
      (CI95%, 64.4%-69.6%); in 1997, 35.0% (CI95%, 33.3%-38.3%); in 2007, 31.9% (CI95%,
      29.6%-34.2%) and in 2017, 21.2% (CI95%, 19.0%-23.3%). In the fifty years covered
      by the study the decline in prevalence was 45.8%, which represents an average
      annual decline of 0.9%.The decline was statistically significant between 1967 and
      1997, and between 2007 and 2017. The four studies demonstrate that infection
      prevalence increased depending on age. The infection rate for 1967 was 1.0% per
      year and declined in the next studies to 0.8% in 1997, 0.8% in 2007, and 0.5% in
      2017. Donors from the last study responded to a survey that showed a
      statistically significant correlation between seroprevalence of Toxoplasma gondii
      antibodies and lack of tap water, unfinished secondary studies or residence in
      the western or southern part of the Buenos Aires metropolitan area. No
      significant association was found with having a cat as a pet, the consumption of
      undercooked meat or the practice of gardening.

PMID- 29223939
TI  - [Papillary fibroelastoma: retrospective analysis. Clinical presentation and
      surgical results].
AB  - Papillary ibroelastomas are small benign intracardiac tumors known for their
      embolic potential. Since the introduction of echocardiography with improved
      resolution and transesophageal imaging techniques, they are being increasingly
      detected in clinical practice. In recent series, papillary fibroelastoma is
      considered the most frequent benign tumor of the heart. Our objective was to
      analyze characteristics and midterm surgical outcome of histologically-confirmed
      cases of papillary fibroelastoma. We conducted a retrospective study on patients
      with cardiac tumors submitted to surgical excision between June 1992 and February
      2017. Out of 108 patients, 18 had papillary fibroelastomas. Their mean age was 58
      years (22-77); 10 were men. The most frequent localizations were the aortic valve
      (7) and the mitral valve (5). None had significant valvular dysfunction. By
      transesophageal echocardiography, the tumor size (larger diameter) was 13.33 +/-
      5.55 mm (6.6-28.0). Two patients, both with tumor in the aortic valve, had
      suffered a stroke; other two had dyspnoea and atrial flutter, respectively. The
      remaining 14 patients were asymptomatic and their tumors were incidental
      findings. In 15 patients the valve was preserved. There was neither surgical
      mortality nor recurrence after 2.6 years of follow-up. In conclusion, most
      papillary fibroelastomas can be surgically removed with valve preservation and
      favorable clinical outcome. However, until the results of randomized trials
      support the decision, an aggressive surgical approach in asymptomatic patients
      needs to be defined in the context of surgical expertise.

PMID- 29223940
TI  - [When to consult the institutional bioethics committee? The deliberative method
      for resolving possible dilemmas].
AB  - In healthcare, an ethical concern that arises during the decision making process
      is considered to be a bioethical dilemma. It is often the case that in the
      absence of proper deliberation, the problem is transferred to a bioethics
      committee, not even representing precisely a dilemma. Bioethics emerged as a
      discipline in the mid-20th century. It is defined as a support to decision-making
      in ethical dilemmas centered on two aspects: ethics of clinical investigation,
      focused on protecting the rights of research subjects, and bioethics in medical
      practice, of an advisory nature. To recognize the difference among difficult or
      complex clinical circumstances and ethical dilemmas could allow knowing when it
      is necessary to request for advice of a committee. It is not so much a question
      of deciding what is right or wrong, but which is the most advisable solution to a
      problem. We review the history of Bioethics Committees in Argentina that are
      facing today the challenge of promoting social responsibility and opening
      deliberations to community and health professionals. In the 20th century two
      historical moments are recognized: a pioneering and slow first period, and a
      second one of legal regulatory framework. Considering deliberation as a method of
      ethics, this article proposes a case analysis procedure and the deliberative
      method to elucidate dilemmas, with or without the help of a Committee.

PMID- 29223941
TI  - [Medical futility and family obstinacy in intensive therapy. When to stop and
      when to keep going?]
AB  - There have been several recent publications related to therapeutic obstinacy and
      futility in the Intensive Care Unit. However, little has been published about
      "the family obstinacy" in persisting with invasive measures in seriously ill
      patients, despite the appropriate information provided to them about the
      patient's poor short-term prognosis. On certain occasions, these critical
      patients are unable to make decisions on the proposed treatments and,
      unfortunately, many of them have not previously indicated their preferences in
      terms of limits to invasive measures (advanced directives). Thus, the patient's
      relatives are the ones who finally assume this arduous task and, in several
      occasions, they make decisions that do not correspond with the patient's actual
      wishes. Palliative medicine is of invaluable help in the difficult goal of
      improving communication among doctors, patients and patients relatives. Limits to
      intervention can be difficult and vague, generating multiple problems in the
      decision-making process. On certain occasions and despite adequate information
      provided by therapists and palliative care doctors, patients' relatives do not
      accept professional directives indicating to stop invasive interventions.
      Understanding futility justification may be relevant to the appropriate
      resolution of these disputes. In this article, we intend to discuss the subject
      "futility in Intensive Care Unit" and how to face the seldom addressed "family
      obstinacy" issue in potentially unrecoverable situations, despite adequate
      medical information.

PMID- 29223942
TI  - [Rho GTPases as molecular targets in cancer. Strategies and therapeutic
      opportunities].
AB  - Rho GTPases are molecular switches that control the different cellular processes.
      Deregulation of these proteins is associated to transformation and malignant
      progression in several cancer types. Given the evidence available of the role of
      Rho GTPases in cancer it is suggested that these proteins can serve as potential
      therapeutic targets. This review focuses on the strategies used to develop Rho
      GTPases modulators and their potential use in therapeutic settings.

PMID- 29223943
TI  - [Pulmonary thromboembolism and aortic dissection: an infrequent presentation].

PMID- 29223944
TI  - [Pancreatic arteriovenous malformation as cause of acute pancreatitis treated by
      endovascular access].
AB  - Arteriovenous malformation in the pancreas is a rare anatomic abnormality that
      may produce acute pancreatitis. The diagnosis was suspected by computed
      tomography with intravenous contrast and by magnetic resonance imaging and it was
      confirmed by arteriography of the celiac trunk and superior mesenteric artery.
      The treatment received was endovascular, although the other valid option for the
      treatment of this disease is the surgical resection. The objective of this
      communication is to present a case of acute pancreatitis due to arteriovenous
      malformation treated by endovascular approach.

PMID- 29223945
TI  - [Heart transplantation in an HIV-infected patient].
AB  - Because of its own unfavourable evolution, HIV infection was until recently
      considered a contraindication for organ transplantation. The introduction of
      highly active antiretroviral therapy prolonged the life expectancy of these
      patients and allowed the manifestation of disorders directly or indirectly
      related to HIV infection, mainly liver, kidney and cardiovascular diseases. We
      present a case of cardiac transplantation due to dilated cardiomyopathy that was
      performed in a patient with a recently detected HIV infection. At 24 month follow
      up, the patient is in very good health status, his CD4 are increasing and the
      viral load is undetectable. He did not present transplant rejection or any other
      complication. To our knowledge, there is no previous publication on heart
      transplantation in patients with HIV in South America. In view of the successful
      outcome of our case and of the few cases reported in the international
      literature, we consider that heart transplantation is a therapeutic option in
      correctly selected HIV patients.

PMID- 29223946
TI  - [Quality of the exo-endocervical sampling in the prevention of uterine cervix
      cancer].
AB  - Cervical and vaginal cytology, Papanicolaou test (PAP), is the most effective
      test for screening of preneoplastic lesions, and cervical cancer prevention. Its
      sensitivity goes from 50 to 98%, according to different statistics, and this
      variation is related to the sampling procedure. A satisfactory smear should be
      taken from the transformation zone, the junction between endocervix and
      exocervix. According to Bethesda, metaplastic and/or endocervical cells should be
      observed under the microscope. The traditional PAP smear includes an exo
      endocervical sampling using the Ayre spatula; however, only near 50% of the
      smears are representative of the transformation zone. In this case report, we
      present the case of a 40-year-old woman who had negative cytology in five
      consecutive annual PAP smears, none of which showed metaplastic or endocervical
      cells. A new sample evidenced a carcinoma in situ (HSIL: high-grade squamous
      intraepithelial lesion). We emphasize the importance of performing a correct exo
      endocervical sampling to allow prompt detection of all premalignant lesions and
      to prevent cervical cancer, which still persists with high mortality worldwide.

PMID- 29223947
TI  - [Trigeminy of ventricular bigeminy caused by reentrant mechanism: reentry of
      reentry].
AB  - The process that follows an acute myocardial infarction generates an appropriate
      substrate for the formation of reentry circuits, considered to be the most
      frequent mechanism of ventricular extrasystoles and tachyarrhythmias. We present
      the case of a patient with an acute myocardial infarction unusually concurring
      with ventricular trigeminy coupled to ventricular bigeminated extrasystoles
      giving rise to a trigeminy sequence over the bigeminy, which indicates the
      existence of two reentry circuits (reentry of reentry) that trigger ventricular
      flutter.

PMID- 29223948
TI  - [Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy].
AB  - In a series of nine patients with histopathological diagnosis of hypersensitivity
      pneumonitis, we retrospectively evaluated clinical data, exposure related
      factors, pulmonary function tests and chest computed tomography scans. A
      restrictive abnormality with reduction of diffusion capacity for carbon monoxide
      was mainly found. Chest scans showed fibrotic patterns in most cases; ground
      glass attenuation areas with mosaic pattern and consolidation in the rest.
      Exposure to avian antigens, cereal grains and air conditioners contaminated with
      fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the
      cases. Since there are no unique features that allow differentiation from other
      interstitial lung diseases, a high clinical suspicion is required and a careful
      search of environmental exposure to possible antigens is needed that, together
      with clinical, radiological and pathological data, may lead to diagnosis.

PMID- 29223949
TI  - [Will the CRISPR / CAS9 system change the genome of humanity?]

PMID- 29223950
TI  - [Nobel Prize in Physiology or Medicine 2017. Our complex inner rhythms].

PMID- 29223951
TI  - Heart rate variability in bipolar disorder and borderline personality disorder: a
      clinical review.
AB  - Heart rate variability (HRV) in psychiatric disorders has become an increasing
      area of interest in recent years following technological advances that enable non
      invasive monitoring of autonomic nervous system regulation. However, the clinical
      interpretation of HRV features remain widely debated or unknown. Standardisation
      within studies of HRV in psychiatric disorders is poor, making it difficult to
      reproduce or build on previous work. Recently, a Guidelines for Reporting
      Articles on Psychiatry and Heart rate variability checklist has been proposed to
      address this issue. Here we assess studies of HRV in bipolar disorder and
      borderline personality disorder against this checklist and discuss the
      implication for ongoing research in this area.

PMID- 29223952
TI  - Isolated myeloperoxidase expression in pediatric B/myeloid mixed phenotype acute
      leukemia is linked with better survival.

PMID- 29223953
TI  - Potential role for acupuncture in the treatment of food addiction and obesity.
AB  - Addressing the global obesity epidemic requires innovative approaches that are
      also acceptable to affected individuals. There is growing evidence suggesting
      that food addiction, one contributor to obesity, bears many similarities to drug
      and alcohol addiction, presenting a potential role for addiction-focused
      acupuncture as a novel treatment modality. In this perspective article, we begin
      by briefly reviewing the evidence linking food and drug/alcohol addiction. We
      then describe the development of an acupuncture-based protocol for treating
      opioid addiction in Hong Kong in the 1970s and discuss the evidence base for
      acupuncture's efficacy in treating a range of substance use disorders. Next, we
      describe acupuncture's proposed mechanism of action in attenuating withdrawal and
      promoting abstinence. Finally, we note the dearth of studies specifically
      examining the effectiveness of acupuncture in treating food addiction and suggest
      that more research should focus in this area as part of the effort to combat
      rising rates of obesity worldwide.

PMID- 29223955
TI  - High-Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After
      Cardiac Surgery.
AB  - BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with
      increased short- and long-term mortality. Inflammation, oxidative stress, and
      endothelial dysfunction and damage play important roles in the development of
      AKI. High-density lipoproteins (HDLs) have anti-inflammatory and antioxidant
      properties and improve endothelial function and repair. Statins enhance HDL's
      anti-inflammatory and antioxidant capacities. We hypothesized that a higher
      preoperative HDL cholesterol concentration is associated with decreased AKI after
      cardiac surgery and that perioperative statin exposure potentiates this
      association. METHODS AND RESULTS: We tested our hypothesis in 391 subjects from a
      randomized clinical trial of perioperative atorvastatin to reduce AKI after
      cardiac surgery. A 2-component latent variable mixture model was used to assess
      the association between preoperative HDL cholesterol concentration and
      postoperative change in serum creatinine, adjusted for known AKI risk factors and
      suspected confounders. Interaction terms were used to examine the effects of
      preoperative statin use, preoperative statin dose, and perioperative atorvastatin
      treatment on the association between preoperative HDL and AKI. A higher
      preoperative HDL cholesterol concentration was independently associated with a
      decreased postoperative serum creatinine change (P=0.02). The association between
      a high HDL concentration and an attenuated increase in serum creatinine was
      strongest in long-term statin-using patients (P=0.008) and was further enhanced
      with perioperative atorvastatin treatment (P=0.004) and increasing long-term
      statin dose (P=0.003). CONCLUSIONS: A higher preoperative HDL cholesterol
      concentration was associated with decreased AKI after cardiac surgery.
      Preoperative and perioperative statin treatment enhanced this association,
      demonstrating that pharmacological potentiation is possible during the
      perioperative period. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

PMID- 29223954
TI  - Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With
      Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials.
AB  - BACKGROUND: We sought to examine the efficacy and safety of 2 PCSK9 (proprotein
      convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab.
      METHODS AND RESULTS: We performed a systematic review and meta-analysis of
      randomized controlled trials comparing treatment with and without PCSK9
      inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean
      follow-up: 85.5 weeks) were included. Mean age was 61.0+/-2.8 years, and mean
      baseline low-density lipoprotein cholesterol was 106+/-22 mg/dL. Compared with no
      PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a
      lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95%
      confidence interval (CI), 0.64-0.81]; P<0.001), stroke (1.0% versus 1.4%; OR:
      0.80 [95% CI, 0.67-0.96]; P=0.02), and coronary revascularization (4.2% versus
      5.8%; OR: 0.78 [95% CI, 0.71-0.86]; P<0.001). Overall, no significant change was
      observed in all-cause mortality (OR: 0.71 [95% CI, 0.47-1.09]; P=0.12) or
      cardiovascular mortality (OR: 1.01 [95% CI, 0.85-1.19]; P=0.95). A significant
      association was observed between higher baseline low-density lipoprotein
      cholesterol and benefit in all-cause mortality (P=0.038). No significant change
      was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88-1.42];
      P=0.37), myalgia (OR: 0.95 [95% CI, 0.75-1.20]; P=0.65), new onset or worsening
      of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95-1.17]; P=0.32), and
      increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70-1.01]; P=0.06) or
      alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82-1.12]; P=0.61).
      CONCLUSIONS: Treatment with a PCSK9 inhibitor is well tolerated and improves
      cardiovascular outcomes. Although no overall benefit was noted in all-cause or
      cardiovascular mortality, such benefit may be achievable in patients with higher
      baseline low-density lipoprotein cholesterol.

PMID- 29223956
TI  - Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions
      in Very-Low-Density Lipoproteins.
AB  - BACKGROUND: It is uncertain whether pharmacological reductions in very-low
      density lipoproteins (VLDLs), and their component triglyceride and cholesterol
      could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD)
      events among individuals in whom low-density lipoprotein cholesterol (LDL-C) has
      been adequately lowered. We examined whether individuals with greater on-statin
      reductions in VLDL-related measures-beyond reductions in LDL-C-were at further
      reduced risk of ASCVD. METHODS AND RESULTS: In 9423 participants in the JUPITER
      (Justification for the Use of Statins in Prevention) trial (NCT00239681), at
      baseline and on statin we measured standard lipids, 400-MHz proton nuclear
      magnetic resonance spectroscopy-measured VLDL particle subclasses (small, medium,
      and large VLDL lipoprotein particle concentration), and total VLDL cholesterol
      mass. Compared with individuals allocated to placebo, we examined risk of
      incident ASCVD (N=211) among statin-allocated participants who achieved minimal
      (<median) or greater (>=median) marker reductions using adjusted Cox models. On
      statin changes in VLDL-related markers were only modestly correlated (Spearman
      r<=0.29) with change in LDL-C. On-statin median LDL-C was 54 mg/dL and
      triglyceride was 101 mg/dL. Dose-response reductions in ASCVD risk were observed
      for greater reductions in LDL-C, VLDL cholesterol mass, and small VLDL
      lipoprotein particle concentration; the latter 2 remained significant after
      incremental adjustment for change in LDL-C (P<=0.006). Conversely, there was no
      further risk reduction with greater reductions in triglycerides or large/medium
      VLDL lipoprotein particle concentration. CONCLUSIONS: Pharmacological reduction
      in small, cholesterol-enriched, triglyceride-depleted VLDL was associated with
      reduction in ASCVD risk. Chemically measured triglycerides may not sufficiently
      capture risk related to VLDL pathways. These findings also support broader
      profiling of lipid and lipoprotein changes in response to statins as prognostic
      markers of individual benefit, supporting more precision-medicine, individualized
      approaches to cardiovascular risk reduction. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT00239681.

PMID- 29223957
TI  - Prognostic Utility of Morning Blood Pressure Surge for 20-Year All-Cause and
      Cardiovascular Mortalities: Results of a Community-Based Study.
AB  - BACKGROUND: Morning blood pressure (BP) surge (MS), defined by the MS amplitude,
      is an independent prognostic factor of cardiovascular outcomes in some, but not
      all, populations. METHOD AND RESULTS: We enrolled 2020 participants (1029 men;
      aged 30-79 years) with 24-hour ambulatory BP data. During a median 19.7-year
      follow-up, 607 deaths (182 by cardiovascular causes) were confirmed from the
      National Death Registry. The amplitude of sleep-trough MS (STMS) was derived from
      the difference between morning systolic BP (SBP) and lowest nighttime SBP. The
      rate of STMS was derived as the slope of linear regression of sequential SBP
      measures on time intervals within the STMS period. Thresholds for high STMS
      amplitude and rate were determined by the 95th percentiles (43.7 mm Hg and 11.3
      mm Hg/h, respectively). Multivariable Cox models, adjusting for age, sex, body
      mass index, smoking, alcohol, low-density lipoprotein cholesterol, 24-hour SBP,
      night:day SBP ratio, and antihypertensive treatment, revealed that a high STMS
      rate (hazard ratio, 1.666; 95% confidence interval, 1.185-2.341), but not STMS
      amplitude (hazard ratio, 1.245; 95% confidence interval, 0.984-1.843), was
      significantly associated with a greater mortality risk. Similarly, STMS rate
      (hazard ratio, 2.608; 95% confidence interval, 1.554-4.375), but not STMS
      amplitude, was significantly associated with the risk of cardiovascular mortality
      (hazard ratio, 0.966; 95% confidence interval, 0.535-1.747). Moreover, the
      prognostic values of STMS rate were comparable in subjects with or without
      morning and nocturnal hypertension (P>0.05 for interaction for all). In
      simulation studies, STMS rate was less susceptible to measurement errors of the
      sleep-trough SBP than STMS amplitude. CONCLUSIONS: STMS rate could independently
      help identify subjects with an increased cardiovascular risk.

PMID- 29223958
TI  - Point-of-care tests for STIs: the way forward.

PMID- 29223959
TI  - Performance and operational characteristics of point-of-care tests for the
      diagnosis of urogenital gonococcal infections.
AB  - BACKGROUND: In 2012, there was an estimated 78 million new cases of gonorrhoea
      globally. Untreated infection may lead to reproductive and neonatal morbidity and
      facilitate HIV transmission. Diagnosis and treatment are a priority for control
      and prevention, yet use of point-of-care tests (POCTs) for Neisseria gonorrhoeae
      (NG) is limited. OBJECTIVES: To review the performance and operational
      characteristics of NG POCTs for diagnosis of urogenital gonorrhoea. METHODS: We
      compiled and synthesised findings from two separate systematic reviews which
      included evaluations published until August 2015. RESULTS: Six tests were
      included: five were immunochromatographic tests (ICTs) or optical immunoassay
      (OIAs) based on antigen detection; with 5-7 steps and results in 25-40 min, and
      one (GeneXpert CT/NG) was a 'near-patient test' based on nucleic acid
      amplification technique (NAAT); with three steps, electricity required, and
      results in 90 min. When compared with laboratory-based NAATs as the reference
      tests, sensitivities of ICT and OIA-based POCTs ranged from 12.5% to 70% when
      cervical/vaginal swabs were tested. Specificities ranged from 89% to 99.8%. The
      near-patient NAAT had sensitivities of >95% and specificities of >99.8%
      consistently across all specimen types (urine, cervical and vaginal swabs).
      CONCLUSIONS: Based on a limited number of evaluations, antigen detection POCTs
      for NG lacked sufficient sensitivity to be used for screening. A near-patient
      NAAT has acceptable performance, only involved a few steps, but needs
      electricity, a temperature-controlled environment and has a 90 min run time. To
      achieve wider scale up of NG POCTs, we need strong evidence of cost
      effectiveness, which should inform guidelines and ultimately increase test
      development, demand and reduce costs.

PMID- 29223960
TI  - Systematic reviews of point-of-care tests for the diagnosis of urogenital
      Chlamydia trachomatis infections.
AB  - BACKGROUND: WHO estimates that 131 million new cases of urogenital Chlamydia
      trachomatis (CT) infections occur globally every year. Most infections are
      asymptomatic. Untreated infection in women can lead to severe complications.
      Screening and treatment of at-risk populations is a priority for prevention and
      control. OBJECTIVES: To summarise systematic reviews of the performance
      characteristics of commercially available point-of-care tests (POCT) for
      screening and diagnosis of urogenital CT infection. METHODS: Two separate
      systematic reviews covering the periods 2004-2013 and 2010-2015 were conducted on
      rapid CT POCTs. Studies were included if tests were evaluated against a valid
      reference standard. RESULTS: In the first review, 635 articles were identified,
      of which 11 were included. Nine studies evaluated the performance of eight
      antigen detection rapid POCTs on 10 280 patients and two studies evaluated a near
      patient nucleic acid amplification test (NAAT) on 3518 patients. Pooled
      sensitivity of antigen detection tests was 53%, 37% and 63% for cervical swabs,
      vaginal swabs and male urine, and specificity was 99%, 97% and 98%, respectively.
      The pooled sensitivity and specificity of the near-patient NAAT for all specimen
      types were >98% and 99.4%, respectively. The second review identified two
      additional studies on four antigen detection POCTs with sensitivities and
      specificities of 22.7%-37.7% and 99.4%-100%, respectively. A new two-step 15 min
      rapid POCT using fluorescent nanoparticles showed performance comparable to that
      of near-patient NAATs. CONCLUSIONS: The systematic reviews showed that antigen
      detection POCTs for CT, although easy to use, lacked sufficient sensitivity to be
      recommended as a screening test. A near-patient NAAT shows acceptable performance
      as a screening or diagnostic test but requires electricity, takes 90 min and is
      costly. More affordable POCTs are in development.

PMID- 29223961
TI  - A systematic review and meta-analysis of studies evaluating the performance of
      point-of-care tests for human papillomavirus screening.
AB  - BACKGROUND: High-risk human papillomavirus (HPV) is a necessary cause of high
      grade cervical intraepithelial neoplasia (grade 2 or higher, CIN2+). Simplified
      and rapid HPV DNA assays designed for use in resource-limited settings have
      recently become available. METHODS: We performed a systematic review and meta
      analysis by searching Medline, Embase, Global Health and CINAHL databases for
      studies from 1 January 2004 to 25 February 2017 that reported the performance of
      careHPV or OncoE6 for the detection of histological CIN2+ in cervical cancer
      screening. We used bivariate models to estimate pooled sensitivity and
      specificity for CIN2+ and CIN3+. RESULTS: A total of 29 657 women were included
      from seven studies evaluating the performance of careHPV for the detection of
      CIN2+ and four studies among 27 845 women for the detection of CIN3+. The pooled
      prevalence for CIN2+ and CIN3+ was 2.3% and 1.1%, respectively. careHPV had
      sensitivity and specificity of 88.1% (95% CI 81.4 to 92.7) and 83.7% (95% CI 74.9
      to 89.8), respectively, for CIN2+ and 90.3% (95% CI 83.4 to 94.5) and 85.3% (95%
      CI 73.1 to 92.5), respectively, for CIN3+, using clinician-collected cervical
      specimen. The corresponding pooled estimates using self-collected vaginal swabs
      were 73.6% (95% CI 64.9 to 80.8) and 88.0% (95% CI 79.1 to 93.5) for CIN2+ and
      75.2% (95% CI 66.8 to 82.0) and 90.6% (95% CI 83.4 to 94.9) for CIN3+. Two
      studies using OncoE6 reported sensitivity and specificity ranging from 31.3% to
      42.4% and 99.1%-99.4% for CIN2+, and 53.5% and 98.9% for CIN3+ for one study.
      CONCLUSION: CareHPV has good sensitivity and specificity for the detection of
      CIN2+ and CIN3+, but sensitivity was lower using self-collected vaginal samples.
      The specificity is lower in high HPV prevalence populations such as women living
      with HIV. OncoE6 assay warrants further evaluation.

PMID- 29223962
TI  - Evaluation of seven rapid tests for syphilis available in Brazil using
      defibrinated plasma panels.
AB  - OBJECTIVES: In 2012, the WHO estimated that 6 million new cases of syphilis per
      year would occur worldwide, including 937 000 in Brazil. Early diagnosis and
      treatment of syphilis are essential to reduce morbidity and prevent transmission.
      The availability of rapid tests (RTs) for this diagnosis means that testing can
      be performed more quickly, as a point-of-care test, even in non-laboratory
      environments and requires only simple technical training to antibodies detection.
      The objective of this study was to evaluate the performance and operational
      aspects of seven commercially available RTs for syphilis in Brazil. METHODS:
      Seven rapid treponemal tests were evaluated for sensitivity, specificity,
      accuracy and Kappa value, according to a panel composed of 493 members. The
      operational performance of the assay was also determined for these tests.
      RESULTS: The seven RTs showed sensitivity ranging from 94.5% to 100% when
      compared with the reference tests and specificity of between 91.5% and 100%. All
      the RTs evaluated presented good operational performance, and only one failed to
      present the minimum specificity as defined by Brazil's Ministry of Health.
      CONCLUSION: All the tests presented good operational performance, and the
      professionals who performed them considered them to be easy to use and interpret.
      This evaluation is important for making informed choices of tests to be used in
      the Brazilian Unified Health System.

PMID- 29223963
TI  - Field evaluation of two point-of-care tests for syphilis among men who have sex
      with men, Verona, Italy.
AB  - OBJECTIVES: The incidence of HIV and syphilis among men who have sex with men
      (MSM) in Europe has recently increased. Rapid point-of-care tests (POCTs) for
      syphilis can improve access to screening. The purpose of this study was to
      evaluate the performance of two syphilis POCTs compared with laboratory tests
      among MSM. METHODS: The study was undertaken in Verona, Italy. Asymptomatic MSM,
      potentially exposed to syphilis, were enrolled prospectively. The POCTs evaluated
      were SD Bioline Syphilis 3.0 and Chembio DPP Syphilis Screen & Confirm Assay on
      both serum and fingerprick blood. The results of the POCTs were read by the naked
      eye by two independent readers and their concordance assessed. RESULTS: A total
      of 289 MSM were enrolled in the study. Based on laboratory tests, 35 MSM (12.1%)
      were TPPA-positive alone and 16 (5.5%) were both Treponema pallidum particle
      agglutination test (TPPA) and rapid plasma reagin (RPR)-positive. The
      specificities of both POCTs were above 99% on both serum and fingerstick blood
      specimens, while sensitivities varied considerably. The sensitivity of the SD
      Bioline test was lower on fingerprick blood (51.4% and 54.3%, readers 1 and 2,
      respectively) compared with that on serum (80.0% and 82.9%). In contrast, the
      Chembio test exhibited similar sensitivity values for serum and fingerprick
      samples (57.7% and 64.0% on serum vs 65.4% and 69.2% on fingerprick for the
      treponemal component; 63.6% on both samples by both readers for the non
      treponemal component). The positive predictive value ranged between 100% and
      93.9% for the treponemal component of both syphilis POCTs, but was lower (76.3%
      100%)%) for the non-treponemal component of the Chembio POCT. The negative
      predictive value surpassed 90% for both tests on both samples. The agreement
      between readers was very high (>99%). CONCLUSION: The diagnostic performance of
      the syphilis POCTs was lower than expected; however, considering the prevalence
      of syphilis among MSM, POCTs should be recommended to improve syphilis detection
      among MSM.

PMID- 29223964
TI  - Assessing stakeholder perceptions of the acceptability and feasibility of
      national scale-up for a dual HIV/syphilis rapid diagnostic test in Malawi.
AB  - OBJECTIVES: The WHO recommends pregnant women receive both HIV and syphilis
      testing at their first antenatal care visit, as untreated maternal infections can
      lead to severe, adverse pregnancy outcomes. One strategy for increasing testing
      for both HIV and syphilis is the use of point-of-care (rapid) diagnostic tests
      that are simple, proven effective and inexpensive. In Malawi, pregnant women
      routinely receive HIV testing, but only 10% are tested for syphilis at their
      first antenatal care visit. This evaluation explores stakeholder perceptions of a
      novel, dual HIV/syphilis rapid diagnostic test and potential barriers to national
      scale-up of the dual test in Malawi. METHODS: During June and July 2015, we
      conducted 15 semistructured interviews with 25 healthcare workers, laboratorians,
      Ministry of Health leaders and partner agency representatives working in
      prevention of mother-to-child transmission in Malawi. We asked stakeholders about
      the importance of a dual rapid diagnostic test, concerns using and procuring the
      dual test and recommendations for national expansion. RESULTS: Stakeholders
      viewed the test favourably, citing the importance of a dual rapid test in
      preventing missed opportunities for syphilis diagnosis and treatment, improving
      infant outcomes and increasing syphilis testing coverage. Primary technical
      concerns were about the additional procedural steps needed to perform the test,
      the possibility that testers may not adhere to required waiting times before
      interpreting results and difficulty reading and interpreting test results.
      Stakeholders thought national scale-up would require demonstration of cost
      savings, uniform coordination, revisions to testing guidelines and algorithms,
      training of testers and a reliable supply chain. CONCLUSIONS: Stakeholders
      largely support implementation of a dual HIV/syphilis rapid diagnostic test as a
      feasible alternative to current antenatal testing. Scale-up will require
      addressing perceived barriers; negotiating changes to existing algorithms and
      guidelines; and Ministry of Health approval and funding to support training of
      staff and procurement of supplies.

PMID- 29223965
TI  - Advancing prevention of sexually transmitted infections through point-of-care
      testing: target product profiles and landscape analysis.
AB  - OBJECTIVES: Advancing the field of point-of-care testing (POCT) for STIs can
      rapidly and substantially improve STI control and prevention by providing
      targeted, essential STI services (case detection and screening). POCT enables
      definitive diagnosis and appropriate treatment in a single visit and home and
      community-based testing. METHODS: Since 2014, the WHO Department of Reproductive
      Health and Research, in collaboration with technical partners, has completed four
      landscape analyses of promising diagnostics for use at or near the point of
      patient care to detect syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis,
      Trichomonas vaginalis and the human papillomavirus. The analyses comprised a
      literature review and interviews. Two International Technical Consultations on
      STI POCTs (2014 and 2015) resulted in the development of target product profiles
      (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management,
      public health and epidemiology participated in the consultations with
      representation from all WHO regions. RESULTS: The landscape analysis identified
      diagnostic tests that are either available on the market, to be released in the
      near future or in the pipeline. The TPPs specify 28 analytical and operational
      characteristics of POCTs for use in different populations for surveillance,
      screening and case management. None of the tests that were identified in the
      landscape analysis met all of the targets of the TPPs. CONCLUSION: More efforts
      of the global health community are needed to accelerate access to affordable
      quality-assured STI POCTs, particularly in low- and middle-income countries, by
      supporting the development of new diagnostic platforms as well as strengthening
      the validation and implementation of existing diagnostics according to
      internationally endorsed standards and the best available evidence.

PMID- 29223966
TI  - Advancing point of care diagnostics for the control and prevention of STIs: the
      way forward.
AB  - WHO recognises the global impact of sexually transmitted infections (STIs) on
      global public health and individual sexual and reproductive health and well
      being. As a component of the WHO Global Health Sector Strategy for the control
      and prevention of STIs, there has been a growing recognition of the importance of
      integrating point-of-care tests (POCTs) into overall strategic planning. The
      process of integrating STI POCTs, in addition to providing a definitive diagnosis
      and appropriate treatment in a single visit, also includes innovative delivery
      options, such as on-site delivery, community-based testing (including screening),
      as well as self-testing at home after purchase of a test online or over-the
      counter. WHO organised two technical consultations in May 2014 and July 2015.
      This article summarises the discussions of the meeting participants on advancing
      the use of POCTs to control and prevent STIs. The following priorities were
      identified: the need for pathogens' target discovery; encouragement of
      multiplexing, miniaturisation, simplification and connectivity; promotion of
      standardisation of evaluation of new diagnostic platforms across all stages of
      the evaluation pipeline; the need for an investment case, modelling and scenarios
      to ensure buy-in among key stakeholders, including developers and the private
      sector; the need for norms and standards, including guidelines, to support
      introduction of STI POCTs in programmes; anticipating potential tensions between
      different parties at the implementation level; and leveraging on the global
      initiative, Sustainable Development Goals (SDGs)/global health sector STI
      strategy, to sustain investment in STI POCT programmes. There is a rich pipeline
      of diagnostic products, but some have stalled in development. An approach to
      accelerate the evaluation of new diagnostics is to set up a competent network of
      evaluation sites ahead of time, harmonise regulatory approval processes with
      development of models to estimate cost-effectiveness, informed by better STI
      data. This should result in accelerating policy development. Although it may be
      some time before good POCTs can be widely implemented in low resource settings,
      it is important to be a catalyst for continued development and use of these
      essential tools as an integral part of both the WHO Global Health Sector Strategy
      and the agenda for 2030.

PMID- 29223967
TI  - Questionnaire-based algorithm for assessing occupational noise exposure of
      construction workers.
AB  - OBJECTIVES: Occupational noise exposure is a major cause of hearing loss
      worldwide. In order to inform preventative strategies, we need to further
      understand at a population level which workers are most at risk. METHODS: We have
      developed a new questionnaire-based algorithm that evaluates an individual
      worker's noise exposure. The questionnaire and supporting algorithms are embedded
      into the existing software platform, OccIDEAS. Based on the tasks performed by a
      worker during their most recent working shift and using a library of task-based
      noise exposure levels, OccIDEAS estimates whether a worker has exceeded the full
      shift workplace noise exposure limit (LAeq,8h>=85 dBA). We evaluated the validity
      of the system in a sample of 100 construction workers. Each worker wore a
      dosimeter for a full working shift and was then interviewed using the OccIDEAS
      software. RESULTS: The area under the receiver operating characteristic curve was
      0.81 (95% CI 0.72 to 0.90) indicating that the ability of OccIDEAS to identify
      construction workers with an LAeq,8h>=85 dBA was excellent. CONCLUSION: This
      validated noise questionnaire may be useful in epidemiological studies and for
      workplace health and safety applications.

PMID- 29223968
TI  - Do regulations protect workers from occupational exposures to carcinogenic,
      mutagenic and reprotoxic (CMR) agents in France?
AB  - OBJECTIVE: This article explores the impact of regulations on the implementation
      of collective protections in France to occupational exposure to carcinogenic,
      mutagenic and reprotoxic (CMR) agents. METHODS: Individual data from the French
      national cross-sectional survey of occupational hazards conducted in 2010 were
      analysed. We investigated whether stricter regulations and longer exposures were
      associated with higher level of collective protection using multivariate logistic
      regressions. RESULTS: General ventilation, for which effect is limited as
      collective protection for CMR products, was present in 19% of situations
      involving CMR agents while isolation chambers, the most effective form of
      protection, were only very rarely implemented. Multilevel logistic regressions
      show that exposure situations to products classified as category 1 or 2 by the
      European Union do not have a higher probability of benefiting from a collective
      protection measures. Exposures to products with a Binding Occupational Exposure
      Limit Value selectively benefited from a better level of protection. Exposures to
      agents entered on the International Agency for Research on Cancer (IARC) list of
      proven or probable carcinogens benefited more from effective collective
      protections than products suspected to be carcinogens but not yet classified by
      IARC. CONCLUSIONS: These results suggest that the dissemination of evaluations of
      carcinogens by the IARC translate into improved protective measures even though
      the IARC classification has no mandatory impact on regulations.

PMID- 29223970
TI  - Sea Changes.

PMID- 29223969
TI  - It is unclear whether specialist palliative care teleconsultation leads to an
      improvement in patient symptom scores.

PMID- 29223971
TI  - Keeping Pace with the Red Queen: Identifying the Genetic Basis of Susceptibility
      to Infectious Disease.
AB  - Genome-wide association studies are widely used to identify "disease genes"
      conferring resistance/susceptibility to infectious diseases. Using a combination
      of mathematical models and simulations, we demonstrate that genetic interactions
      between hosts and parasites [genotype-by-genotype (G * G) interactions] can
      drastically affect the results of these association scans and hamper our ability
      to detect genetic variation in susceptibility. When hosts and parasites coevolve,
      these G * G interactions often make genome-wide association studies unrepeatable
      over time or across host populations. Reanalyzing previously published data on
      Daphnia magna susceptibility to infection by Pasteuria ramosa, we identify
      genomic regions consistent with G * G interactions. We conclude by outlining
      possible avenues for designing more powerful and more repeatable association
      studies.

PMID- 29223972
TI  - Intravaginal boric acid: is it an alternative therapeutic option for vaginal
      trichomoniasis?
AB  - OBJECTIVES: Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most
      common curable sexually transmitted infection worldwide. Current guidance in the
      UK is to treat TV with a nitroimidazole antibiotic. The high prevalence of TV,
      high rate of antibiotic resistance and limited tolerability to nitroimidazoles
      suggest that alternative treatment regimens are needed. Intravaginal boric acid
      (BA) has been used safely for the treatment of candida vulvovaginitis and
      bacterial vaginosis, and in vitro studies suggest BA is active against TV. We
      review the evidence for the efficacy of BA in patients with TV. METHODS: MEDLINE,
      EMBASE, CINAHL, AMED, HMIC and BNI and Grey literature databases, The Cochrane
      Library, Trial Registers, conference abstracts and proceedings were searched.
      Inclusion criteria were women aged 16 years or over with microbiological
      confirmation of TV infection and using BA as treatment. There were no
      restrictions on language, publication date or study design. The in vitro evidence
      for BA activity against TV was also reviewed. RESULTS: No randomised controlled
      trials or case series were found. Four case reports demonstrated TV clearance
      with BA using a variety of dose regimens (dose 600 mg alternate nights to 600 mg
      two times per day; duration 1-5 months). In vitro studies suggest that BA has
      activity against TV which is independent of its effect on pH. DISCUSSION: Further
      evaluation of BA for the treatment of uncomplicated TV is required, but it may be
      useful when therapeutic options are limited. If shown to be safe and effective,
      intravaginal BA might provide a well-tolerated alternative anti-infective
      treatment which reduces community exposure to systemic antibiotics.

PMID- 29223974
TI  - Media use in children: American Academy of Pediatrics recommendations 2016.

PMID- 29223973
TI  - Chromosomal rearrangements in the 11p15 imprinted region: 17 new 11p15.5
      duplications with associated phenotypes and putative functional consequences.
AB  - BACKGROUND: The 11p15 region contains two clusters of imprinted genes. Opposite
      genetic and epigenetic anomalies of this region result in two distinct growth
      disturbance syndromes: Beckwith-Wiedemann (BWS) and Silver-Russell syndromes
      (SRS). Cytogenetic rearrangements within this region represent less than 3% of
      SRS and BWS cases. Among these, 11p15 duplications were infrequently reported and
      interpretation of their pathogenic effects is complex. OBJECTIVES: To report
      cytogenetic and methylation analyses in a cohort of patients with SRS/BWS
      carrying 11p15 duplications and establish genotype/phenotype correlations.
      METHODS: From a cohort of patients with SRS/BWS with an abnormal methylation
      profile (using ASMM-RTQ-PCR), we used SNP-arrays to identify and map the 11p15
      duplications. We report 19 new patients with SRS (n=9) and BWS (n=10) carrying de
      novo or familial 11p15 duplications, which completely or partially span either
      both telomeric and centromeric domains or only one domain. RESULTS: Large
      duplications involving one complete domain or both domains are associated with
      either SRS or BWS, depending on the parental origin of the duplication. Genotype
      phenotype correlation studies of partial duplications within the telomeric domain
      demonstrate the prominent role of IGF2, rather than H19, in the control of
      growth. Furthermore, it highlights the role of CDKN1C within the centromeric
      domain and suggests that the expected overexpression of KCNQ1OT1 from the
      paternal allele (in partial paternal duplications, excluding CDKN1C) does not
      affect the expression of CDKN1C. CONCLUSIONS: The phenotype associated with 11p15
      duplications depends on the size, genetic content, parental inheritance and
      imprinting status. Identification of these rare duplications is crucial for
      genetic counselling.

PMID- 29223975
TI  - Auras and the risk of seizures with impaired consciousness following epilepsy
      surgery: implications for driving.
AB  - OBJECTIVE: To calculate the chance of a seizure in the next year (COSY) for
      seizures with impaired awareness in those experiencing auras only, those with no
      seizures and those with continuing seizures. Epilepsy surgery is an effective
      treatment for refractory focal epilepsy. Driving is an important factor affecting
      quality of life. In the UK, driving is not permitted if focal seizures with no
      impairment of awareness (auras, simple partial seizures) continue, if there is a
      prior history of seizures with impaired awareness, as will invariably be the case
      in those having epilepsy surgery. Current UK driving regulations allow driving if
      COSY is less than 20%. METHOD: We calculated COSY in 819 epilepsy surgery
      patients with up to 25 years follow-up. Each patient year was graded on the The
      International League against Epilepsy surgery outcome scale. RESULTS: Patients
      who were entirely seizure-free for 1, 2 and 3 years had COSY of 4.9%, 3.5% and
      2.4% respectively. Patients with only auras within the last 1, 2 or 3 years had a
      COSY of 11.3%, 9.2% and 7.8% respectively. CONCLUSIONS: Individuals with auras
      only after epilepsy surgery had a higher COSY than those who were seizure-free.
      If a COSY of below 20% is regarded as an acceptable risk, it may be suggested
      that those with auras only in a given year be allowed to drive. The relative risk
      of these patients causing accidents is lower than population groups such as those
      aged <25 or >75 years, who are permitted to drive.

PMID- 29223976
TI  - Zinc Detoxification: A Functional Genomics and Transcriptomics Analysis in
      Drosophila melanogaster Cultured Cells.
AB  - Cells require some metals, such as zinc and manganese, but excess levels of these
      metals can be toxic. As a result, cells have evolved complex mechanisms for
      maintaining metal homeostasis and surviving metal intoxication. Here, we present
      the results of a large-scale functional genomic screen in Drosophila cultured
      cells for modifiers of zinc chloride toxicity, together with transcriptomics data
      for wild-type or genetically zinc-sensitized cells challenged with mild zinc
      chloride supplementation. Altogether, we identified 47 genes for which knockdown
      conferred sensitivity or resistance to toxic zinc or manganese chloride
      treatment, and >1800 putative zinc-responsive genes. Analysis of the 'omics data
      points to the relevance of ion transporters, glutathione (GSH)-related factors,
      and conserved disease-associated genes in zinc detoxification. Specific genes
      identified in the zinc screen include orthologs of human disease-associated genes
      CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that
      knockdown of red dog mine (rdog; CG11897), a candidate zinc detoxification gene
      encoding an ABCC-type transporter family protein related to yeast cadmium factor
      (YCF1), confers sensitivity to zinc intoxication in cultured cells, and that rdog
      is transcriptionally upregulated in response to zinc stress. As there are many
      links between the biology of zinc and other metals and human health, the 'omics
      data sets presented here provide a resource that will allow researchers to
      explore metal biology in the context of diverse health-relevant processes.

PMID- 29223977
TI  - Growth of Caenorhabditis elegans in Defined Media Is Dependent on Presence of
      Particulate Matter.
AB  - Caenorhabditis elegans are typically cultured in a monoxenic medium consisting of
      live bacteria. However, this introduces a secondary organism to experiments, and
      restricts the manipulation of the nutritional environment. Due to the intricate
      link between genes and environment, greater control and understanding of
      nutritional factors are required to push the C. elegans field into new areas. For
      decades, attempts to develop a chemically defined, axenic medium as an
      alternative for culturing C. elegans have been made. However, the mechanism by
      which the filter feeder C. elegans obtains nutrients from these liquid media is
      not known. Using a fluorescence-activated cell sorting based approach, we
      demonstrate growth in all past axenic C. elegans media to be dependent on the
      presence of previously unknown particles. This particle requirement of C. elegans
      led to development of liposome-based, nanoparticle culturing that allows full
      control of nutrients delivered to C. elegans.

PMID- 29223979
TI  - It's About Time!

PMID- 29223980
TI  - Behavioral Economics and the Future of Biosimilars.

PMID- 29223981
TI  - Champions Rising to the Challenge of Ensuring High-Quality Cancer Care.

PMID- 29223978
TI  - PRC2 Is Dispensable in Vivo for beta-Catenin-Mediated Repression of
      Chondrogenesis in the Mouse Embryonic Cranial Mesenchyme.
AB  - A hallmark of craniofacial development is the differentiation of multiple cell
      lineages in close proximity to one another. The mouse skull bones and overlying
      dermis are derived from the cranial mesenchyme (CM). Cell fate selection of the
      embryonic cranial bone and dermis in the CM requires Wnt/beta-catenin signaling,
      and loss of beta-catenin leads to an ectopic chondrogenic cell fate switch. The
      mechanism by which Wnt/beta-catenin activity suppresses the cartilage fate is
      unclear. Upon conditional deletion of beta-catenin in the CM, several key
      determinants of the cartilage differentiation program, including Sox9, become
      differentially expressed. Many of these differentially expressed genes are known
      targets of the Polycomb Repressive Complex 2 (PRC2). Thus, we hypothesized that
      PRC2 is required for Wnt/beta-catenin-mediated repression of chondrogenesis in
      the embryonic CM. We find that beta-catenin can physically interact with PRC2
      components in the CM in vivo However, upon genetic deletion of Enhancer of Zeste
      homolog 2 (EZH2), the catalytic component of PRC2, chondrogenesis remains
      repressed and the bone and dermis cell fate is preserved in the CM. Furthermore,
      loss of beta-catenin does not alter either the H3K27me3 enrichment levels genome
      wide or on cartilage differentiation determinants, including Sox9 Our results
      indicate that EZH2 is not required to repress chondrogenesis in the CM downstream
      of Wnt/beta-catenin signaling.

PMID- 29223982
TI  - Pazopanib Sensitivity in a Patient With Breast Cancer and FGFR1 Amplification.
AB  - Treatment options for patients with hormone receptor-positive (HR+), HER2
      negative (HER2-) breast cancer and resistance to endocrine therapy remain
      limited. An interesting therapeutic target in these patients is fibroblast growth
      factor receptor 1 (FGFR1). FGFR1 is amplified in approximately 11% of patients
      with breast cancer, especially those with HR+ disease. This report presents a
      patient with metastatic HR+ HER2- breast cancer harboring an FGFR1 amplification
      who was resistant to endocrine therapy but responded to pazopanib, a multi
      tyrosine kinase inhibitor with FGFR-inhibiting activity. Upon pazopanib
      treatment, the patient's brain lesions nearly disappeared, and she experienced
      therapeutic changes in the lung and an improvement of liver function. This case
      suggests that pazopanib may be a promising agent for the treatment of patients
      with breast cancer and FGFR1 amplifications.

PMID- 29223983
TI  - Ensuring Patient Safety and Access in Cancer Care.
AB  - The inability to obtain the right high-quality cancer care in a timely and safe
      manner can have devastating results for patients. As cancer care becomes
      inundated with cutting edge and novel treatments, such as personalized medicine,
      oral chemotherapy, biosimilars, and immunotherapy, new safety challenges are
      emerging at increasing speed and complexity. Moreover, shifting federal
      healthcare policies could have significant implications for the safety and access
      to high-quality and effective cancer care for millions of patients with cancer.
      Challenges and opportunities in ensuring patient access to safe, affordable, and
      high-quality cancer care remain significant within the policy landscape. To
      address these concerns, NCCN hosted the Ensuring Safety and Access in Cancer Care
      Policy Summit in June 2017 to discuss pertinent patient safety issues and access
      implications under the Trump administration, as well as policy and advocacy
      strategies to address these gaps and build on opportunities moving forward.

PMID- 29223985
TI  - External Validation of Generic and Cancer-Specific Risk Stratification Tools in
      Patients With Pulmonary Embolism and Active Cancer.
AB  - Background: Numerous risk stratification tools exist to predict early post
      pulmonary embolism (PE) mortality; however, few were specifically designed for
      use in patients with cancer. This study sought to evaluate the performance of 3
      cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia,
      Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk
      stratification tools for predicting 30-day post-PE mortality in patients with
      active cancer. Methods: We identified consecutive, adult, objectively confirmed
      patients with PE and active cancer presenting to our institution from November
      2010 to January 2014. We calculated the proportion of patients categorized as low
      or high risk by each of the 6 risk stratification tools and determined each
      tools' accuracy for predicting 30-day all-cause mortality. Results: A total of
      124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0%
      with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%,
      16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively).
      Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools
      (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients
      as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and
      38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities
      >96.0%, but classified <19% of patients as low risk; specificity of these tools
      were low (PESI, 6.1%; Hestia, 23.2%). Although the final noncancer tool, GPS,
      classified 43.5% of patients as low risk, it did so with a sensitivity of 52.0%
      and specificity of 42.4%. Conclusions: When risk-stratifying PE in patients with
      active cancer, cancer-specific tools appeared to exhibit better prognostic
      accuracy than their generic counterparts. POMPE-C, RIETE, and the Font criteria
      identified a substantially greater proportion of patients with PE likely to
      survive to 30 days with comparable sensitivity to the generic tools.

PMID- 29223984
TI  - NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal,
      Version 3.2017.
AB  - The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide
      recommendations for the management of patients with high-risk syndromes
      associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for
      Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to
      assess comments from reviewers within their institutions, examine relevant data,
      and reevaluate and update their recommendations. These NCCN Guidelines Insights
      focus on genes newly associated with CRC risk on multigene panels, the associated
      evidence, and currently recommended management strategies.

PMID- 29223986
TI  - KRAS Testing, Tumor Location, and Survival in Patients With Stage IV Colorectal
      Cancer: SEER 2010-2013.
AB  - Purpose:KRAS mutations and tumor location have been associated with response to
      targeted therapy among patients with stage IV colorectal cancer (CRC) in various
      trials. This study performed the first population-based examination of
      associations between KRAS mutations, tumor location, and survival, and assessed
      factors associated with documented KRAS testing. Methods: Patients with stage IV
      adenocarcinoma of the colon/rectum diagnosed from 2010 to 2013 were extracted
      from SEER data. Analyses of patient characteristics, KRAS testing, and tumor
      location were conducted using logistic regression. Cox proportional hazards
      models assessed relationships between KRAS mutations, tumor location, and risk of
      all-cause death. Results: Of 22,542 patients, 30% received KRAS testing, and 44%
      of these had mutations. Those tested tended to be younger, married, and
      metropolitan area residents, and have private insurance or Medicare. Rates of
      KRAS testing also varied by registry (range, 20%-46%). Patients with right-sided
      colon cancer (vs left-sided) tended to be older, female, and black; have
      mucinous, KRAS-mutant tumors; and have a greater risk of death (hazard ratio
      [HR], 1.27; 95% CI, 1.22-1.32). KRAS mutations were not associated with greater
      risk of death in the overall population; however, they were associated with
      greater risk of death among patients with left-sided colon cancer (HR, 1.19; 95%
      CI, 1.05-1.33). Conclusions: This large population-based study showed that among
      patients initially diagnosed with stage IV CRC, right-sided colon cancer was
      associated with greater risk of death compared with left-sided cancer, and KRAS
      mutations were only associated with risk of death in left-sided colon cancer. An
      unexpected finding was that among patients with stage IV disease, right-sided
      cancer was more commonly seen in black patients versus whites. Future studies
      should further explore these associations and determine the role of biology
      versus treatment differences. In addition, use of KRAS testing is increasing, but
      there is wide geographic variation wherein disparities related to insurance
      coverage and rurality may warrant further study.

PMID- 29223987
TI  - Radiosurgery for Brain Metastases: Changing Practice Patterns and Disparities in
      the United States.
AB  - Background: Management of brain metastases typically includes radiotherapy (RT)
      with conventional fractionation and/or stereotactic radiosurgery (SRS). However,
      optimal indications and practice patterns for SRS remain unclear. We sought to
      evaluate national practice patterns for patients with metastatic disease
      receiving brain RT. Methods: We queried the National Cancer Data Base (NCDB) for
      patients diagnosed with metastatic non-small cell lung cancer, breast cancer,
      colorectal cancer, or melanoma from 2004 to 2014 who received upfront brain RT.
      Patients were divided into SRS and non-SRS cohorts. Patient and facility-level
      SRS predictors were analyzed with chi-square tests and logistic regression, and
      uptake trends were approximated with linear regression. Survival by diagnosis
      year was analyzed with the Kaplan-Meier method. Results: Of 75,953 patients,
      12,250 (16.1%) received SRS and 63,703 (83.9%) received non-SRS. From 2004 to
      2014, the proportion of patients receiving SRS annually increased (from 9.8% to
      25.6%; P<.001), and the proportion of facilities using SRS annually increased
      (from 31.2% to 50.4%; P<.001). On multivariable analysis, nonwhite race,
      nonprivate insurance, and residence in lower-income or less-educated regions
      predicted lower SRS use (P<.05 for each). During the study period, SRS use
      increased disproportionally among patients with private insurance or who resided
      in higher-income or higher-educated regions. From 2004 to 2013, 1-year actuarial
      survival improved from 24.1% to 49.6% for patients selected for SRS and from
      21.0% to 26.3% for non-SRS patients (P<.001). Conclusions: This NCDB analysis
      demonstrates steadily increasing-although modest overall-brain SRS use for
      patients with metastatic disease in the United States and identifies several
      progressively widening sociodemographic disparities in the adoption of SRS.
      Further research is needed to determine the reasons for these worsening
      disparities and their clinical implications on intracranial control,
      neurocognitive toxicities, quality of life, and survival for patients with brain
      metastases.

PMID- 29223988
TI  - Prevalence of Physical Problems Detected by the Distress Thermometer and Problem
      List in Patients With Myeloproliferative Disorders.
AB  - Background: Patients with myeloproliferative neoplasms (MPNs) can have a severe
      physical symptom burden over an extended disease trajectory that contributes to
      decreased quality of life. Few studies, however, have characterized which
      patients most frequently consider physical symptoms a problem. This study
      describes the physical symptoms of patients with MPNs and the relationship of
      these symptoms to patient characteristics. Methods: Patients with MPNs (N=117)
      completed questionnaires in a dedicated academic medical center MPN clinic.
      Patients reported demographics (age, race/ethnicity, sex, marital status,
      employment status), disease characteristics (MPN type, time with MPN), and
      whether they were bothered by any of 22 variables in the "Physical Problems" list
      in the Distress Thermometer and Problem List (DT&PL). Results: The median number
      of physical problems endorsed by patients was 2 (median, 2.26; SD, 3.18), with a
      range from 0 to 20. Two-fifths endorsed no physical problems, one-fifth endorsed
      1 problem, and two-fifths endorsed >=2 problems, with fatigue (35.5%), sleep
      (27.1%), pain (21.5%), dry skin/pruritus (18.7%), and memory/concentration
      (16.8%) being the most commonly reported. Non-Caucasian participants reported
      more problems with sleep (P=.050), pain (P=.016), and tingling (P=.026). Patients
      with polycythemia vera (PV) reported more issues with tingling (P=.046) and
      sexual problems (P=.032). Conclusions: Patients with MPNs are more likely to
      report physical symptom bother than to report no bother with multiple physical
      problems on the DT&PL. Patients of minority race/ethnicity and those with PV,
      however, showed heightened prevalence of physical problems-characteristics which
      may be used to triage patients for more intensive symptom management.

PMID- 29223989
TI  - Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United
      States: Lessons From Medicare Part D.
AB  - Background: Drug utilization under Medicare Part D varies significantly by
      geographic region. This study examined the extent to which geographic variation
      in Part D plan characteristics contributes to the variation in choice of initial
      endocrine therapy agent among women with incident breast cancer. Methods: Two
      stage multivariate regression analyses were applied to the 16,541 women
      identified from Medicare claims as having incident breast cancer in 2006-2007.
      The first stage determined the effect of state of residence on the probability of
      having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine
      therapy. The second stage provided estimates of the impact of state-specific Part
      D plan characteristics on variation in choice of initial therapy. Results: There
      was substantial residual geographic variation in the likelihood of using an AI as
      initial endocrine therapy, despite controlling for socioeconomic status, breast
      cancer treatment, and other factors. Regression-adjusted probabilities of
      starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia.
      Results from the second stage revealed that variation in characteristics of Part
      D plans across states explained approximately one-third (30%) of the state-level
      variability in endocrine therapy. A higher number of plans with cost-sharing
      above the mean, greater spread in deductibles, and a greater spread in monthly
      drug premiums were associated with lower adjusted state probabilities of
      initiating an AI. In contrast, a higher number of drug plans with monthly
      premiums above the state mean and higher mean cost-sharing (in dollars) were both
      positively associated with likelihood of starting on an AI. Conclusions: Study
      findings suggest that variation in benefit design of Part D plans accounts for an
      important share of the large and persisting variability in use of AIs-the
      preferred oral therapy for breast cancer.

PMID- 29223990
TI  - Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in
      Oncology.
AB  - Myeloid growth factors (MGFs) are given as supportive care to patients receiving
      myelosuppressive chemotherapy to reduce the incidence of neutropenia. This
      selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen-
      and patient-specific risk factors for the development of febrile neutropenia
      (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN,
      and assessing the risks and benefits of MGF use in clinical practice.

PMID- 29223991
TI  - A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned
      From the ANC Study Group.
AB  - Neutropenia and its complications, including febrile neutropenia (FN), represent
      major toxicities associated with cancer chemotherapy, resulting in considerable
      morbidity, mortality, and costs. The myeloid growth factors such as granulocyte
      colony-stimulating factor (G-CSF) have been shown to reduce the risk of
      neutropenia complications while enabling safe and effective chemotherapy dose
      intensity. Concerns about the high costs of these agents along with limited
      physician adherence to clinical practice guidelines, resulting in both overuse
      and underuse, has stimulated interest in models for individual patient risk
      assessment to guide appropriate use of G-CSF. In a model developed and validated
      by the ANC Study Group, half of patients were classified as high risk and half as
      low risk based on patient-, disease-, and treatment-related factors. This model
      has been further validated in an independent patient population. Physician
      assessed risk of FN, as well as the decision to use prophylactic CSF, has been
      shown to correlate poorly with the FN risk estimated by the model. Additional
      modeling efforts in both adults and children receiving cancer treatment have been
      reported. Identification of patients at a high individual risk for FN and its
      consequences may offer the potential for optimal chemotherapy delivery and
      patient outcomes. Likewise, identification of patients at low risk for
      neutropenic events may reduce costs when such supportive care is not warranted.
      This article reviews and summarizes FN modeling studies and the opportunities for
      personalizing supportive care in patients receiving chemotherapy.

PMID- 29223992
TI  - Controversies Regarding Use of Myeloid Growth Factors in Leukemia.
AB  - This review focuses on the data supporting the use of myeloid growth factors
      (MGFs) in patients being treated for acute myeloid leukemia, acute lymphoblastic
      leukemia, chronic myeloid leukemia, and hairy cell leukemia, for which
      neutropenia is a common complication of treatment. However, due to the lack of
      randomized trial data or conflicting results of clinical studies, comprehensive
      guidelines have been difficult to formulate. Moreover, to date, these diagnoses
      have not been addressed in the NCCN Clinical Practice Guidelines in Oncology
      (NCCN Guidelines) for MGFs. However, in most cases, the general principles have
      been included in the applicable NCCN Guidelines for each individual cancer site.

PMID- 29223993
TI  - Disparities in Adjuvant Endocrine Therapy.

PMID- 29223996
TI  - Metabolic myopathies: a practical approach.
AB  - Metabolic myopathies are a diverse group of rare genetic disorders and their
      associated muscle symptoms may be subtle. Patients may present with indolent
      myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic
      delays are common and clinicians need a high index of suspicion to recognise and
      differentiate metabolic myopathies from other conditions that present in a
      similar fashion. Standard laboratory tests may be normal or non-specific,
      particularly between symptomatic episodes. Targeted enzyme activity measurement
      and next-generation genetic sequencing are increasingly used. There are now
      specific enzyme replacement therapies available, and other metabolic strategies
      and gene therapies are undergoing clinical trials. Here, we discuss our approach
      to the adult patient with suspected metabolic myopathy. We outline key features
      in the history and examination and discuss some mimics of metabolic myopathies.
      We highlight some disorders of glycogen and fatty acid utilisation that present
      in adulthood and outline current recommendations on management.

PMID- 29223997
TI  - More than meets the eye in a 'migraine'.

PMID- 29223998
TI  - Cryptococcal meningitis in apparently immunocompetent patients: association with
      idiopathic CD4+ lymphopenia.
AB  - We present two cases of cryptococcal meningitis in people subsequently diagnosed
      with idiopathic CD4+ lymphopenia. Both presented with new onset headaches without
      sinister features and were sent home on multiple occasions from emergency
      departments. Cryptococcal meningitis in HIV-negative patients poses major
      diagnostic and management problems; the associated mortality is 9%-27%. We
      suggest performing blood and cerebrospinal fluid cryptococcal antigen tests in
      all people with lymphocytic meningitis.

PMID- 29223999
TI  - Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of
      the Levonorgestrel-Releasing Intrauterine System.
AB  - AIM: To evaluate the efficacy and safety of levonorgestrel-releasing intrauterine
      system (LNG-IUS) in the long-term treatment of heavy menstrual blood loss in
      women unrelated to intrauterine pathology. METHODS: One hundred and six parous
      women aged 33-48 years with recurrent heavy menstrual bleeding (HMB) participated
      in this study. The women were followed up for 24 months and were assessed for
      intensity of bleeding both for pre- and post-insertion periods. An LNG-IUS was
      inserted in each patient within 7 days of the start of menstrual flow. The women
      were followed up at 1, 3, 6, 12, 18, and 24 months following the insertion of the
      intrauterine device. RESULTS: One hundred and two women completed the follow-up
      period and had a significant reduction in the amount of menstrual blood loss. The
      LNG-IUS was well tolerated by all women. Pre-treatment of the use of the LNG-IUS,
      endometrial biopsy patterns for irregular proliferative endometrium and for
      atypical simple hyperplasia were 34/106 (32.08%) and 61/106 (57.55%) respectively
      and after treatment no abnormal pathologic findings were determined (p < 0.001).
      CONCLUSION: Our findings indicate that the LNG-IUS is effective for significantly
      reducing the amount of menstrual blood loss in women with HMB.

PMID- 29224000
TI  - The Depression, Anxiety and Stress Scale (DASS-21) as a Screener for Depression
      in Substance Use Disorder Inpatients: A Pilot Study.
AB  - Depression is a common co-morbid disorder in substance use disorder (SUD)
      patients. Hence, valid instruments are needed to screen for depression in this
      subpopulation. In this study, the predictive validity of the Depression, Anxiety
      and Stress Scale (DASS-21) for the presence of a depressive disorder was
      investigated in SUD inpatients. Furthermore, differences between DASS-21 scores
      at intake and those recorded one week after inpatient detoxification were
      assessed in order to determine the measurement point of the assessment of the
      DASS-21 leading to the best predictive validity. The DASS-21 was administered to
      47 patients at intake and shortly after inpatient detoxification. The results of
      the DASS-21 were compared to the Mini International Neuropsychiatric Interview
      (MINI), which served as the gold standard. Levels of sensitivity and specificity
      of 78-89% and 71-76% were found for the DASS-21 assessed after detoxification,
      satisfactorily predicting depression as diagnosed with the MINI. Total DASS-21
      scores as well as the DASS subscale for depression were significantly reduced at
      the second measurement, compared to the DASS at intake. We conclude that the DASS
      21 may be a suitable instrument to screen for depressive disorders in SUD
      patients when administered (shortly) after detoxification. Future research is
      needed to support this conclusion.

PMID- 29224001
TI  - Dental Caries and Developmental Defects of Enamel in the Primary Dentition of
      Preterm Infants: Case-Control Observational Study.
AB  - AIM: Assessment of dental health in the primary dentition of preterm infants
      (PTI) including investigation of mother- and infant-related risk factors in a
      case-control study design. MATERIAL AND METHODS: One hundred twenty-eight infants
      aged 3-4 years were included. Sixty-four PTI (27 males) were randomly selected
      from the preterm registry of the Jena University Hospital. As a control group
      served 64 full-term infants (FTI) recruited from the Department of Paediatric
      Dentistry, matched for age and sex. Dental examinations were provided by one
      dentist under standard clinical conditions. Caries was scored using the
      International Caries Detection and Assessment System (ICDAS II) and the DMFT,
      gingival health using the Periodontal Screening Index, and developmental defects
      of enamel using the DDE index. Mother- and infant-related factors were collected
      via a questionnaire and from medical records. RESULTS: The caries prevalence was
      50.0% (ICDAS II >0) in PTI and 12.5% (ICDAS II >0) in FTI. The caries experience
      was higher in PTI (DMFT 1.0 +/- 3.1) than in FTI (DMFT 0.3 +/- 1.0). PTI had a
      higher risk of caries (OR 7.0), initial lesions (OR 6.2), DDE (OR 7.5), and
      gingivitis (OR 6.5) than FTI. The highest risk occurred in PTI with an extremely
      low birth weight (<1,000 g). A higher risk of DDE was present when mothers
      suffered from illness during pregnancy (OR 3.9). A higher risk of caries was
      revealed in infants with respiratory syndrome (OR 6.2) or when their mothers had
      a lower socioeconomic status (OR 6.3). CONCLUSIONS: PTI had less healthy teeth
      than FTI and are at a higher risk for DDE, caries, and gingivitis. The poorer
      dental health in PTI is associated with a low birth weight, a low socioeconomic
      status, and mothers' illness during pregnancy.

PMID- 29224002
TI  - The Protective Effects of Kappa-Opioid Receptor Stimulation in Hypoxic Pulmonary
      Hypertension Involve Inhibition of Autophagy Through the AMPK-MTOR Pathway.
AB  - BACKGROUND/AIMS: In a previous study, we showed that kappa-opioid receptor
      stimulation with the selective agonist U50,488H ameliorated hypoxic pulmonary
      hypertension (HPH). However, the roles that pulmonary arterial smooth muscle cell
      (PASMC) proliferation, apoptosis, and autophagy play in kappa-opioid receptor
      mediated protection against HPH are still unknown. The goal of the present study
      was to investigate the role of autophagy in U50,488H-induced HPH protection and
      the underlying mechanisms. METHODS: Rats were exposed to 10% oxygen for three
      weeks to induce HPH. After hypoxia, the mean pulmonary arterial pressure (mPAP)
      and the right ventricular pressure (RVP) were measured. Cell viability was
      monitored using the Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was
      detected by flow cytometry and Western blot. Autophagy was assessed by means of
      the mRFP-GFP-LC3 adenovirus transfection assay and by Western blot. RESULTS:
      Inhibition of autophagy by the administration of chloroquine prevented the
      development of HPH in the rat model, as evidenced by significantly reduced mPAP
      and RVP, as well as decreased autophagy. U50,488H mimicked the effects of
      chloroquine, and the effects of U50,488H were blocked by nor-BNI, a selective
      kappa-opioid receptor antagonist. In vitro experiments showed that the inhibition
      of autophagy by chloroquine was associated with decreased proliferation and
      increased apoptosis of PASMCs. Under hypoxia, U50,488H also significantly
      inhibited autophagy, reduced proliferation and increased apoptosis of PASMCs.
      These effects of U50,488H were blocked by nor-BNI. Moreover, exposure to hypoxic
      conditions significantly increased AMPK phosphorylation and reduced mTOR
      phosphorylation, and these effects were abrogated by U50,488H. The effects of
      U50,488H on PASMC autophagy were inhibited by AICAR, a selective AMPK agonist, or
      by rapamycin, a selective mTOR inhibitor. CONCLUSION: Our data provide evidence
      for the first time that kappa-opioid receptor stimulation protects against HPH by
      inhibiting PASMCs autophagy via the AMPK-mTOR pathway.

PMID- 29224004
TI  - ORCA Priorities and State of Play in 2017.

PMID- 29224003
TI  - Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells
      via Immunoglobulin-Like Transcript 2 in Gastric Cancer.
AB  - BACKGROUND/AIMS: Human leukocyte antigen-G (HLA-G) plays an important role in
      inhibiting natural killer (NK) cell function and promoting immune escape.
      However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not
      well understood. This study investigated the expression of HLA-G in GC and the
      role of HLA-G-effected NK cells in GC progression. METHODS: HLA-G expression in
      GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry
      and western blot. The number of tumor-infiltrating NK cells and the expression of
      their surface receptors were analyzed by immunohistochemistry and flow cytometry,
      respectively. The effect of HLA-G on NK cell proliferation was examined by Cell
      Counting Kit-8 (CCK8) assay. LDH release assay was used to evaluate the effect of
      HLA-G on the cytotoxic activity of NK cells, and the levels of IFN-gamma and TNF
      alpha in the co-cultured supernatant were detected by ELISA. Mice bearing a
      xenograft tumor model were used to examine the effect of HLA-G on the anti-tumor
      effect of NK cells. RESULTS: HLA-G positive expression was detected in most of
      the GC tissues, and was correlated with the adverse prognosis of the disease. The
      expression of HLA-G was negatively associated with the number of tumor
      infiltrating NK cells. Furthermore, GC cell lines with overexpressed HLA-G
      revealed their ability to inhibit the cell proliferation and cytotoxic activity
      of NK-92MI cells, and reduce the secretion of IFN-gamma and TNF-alpha through
      immunoglobulin-like transcript 2 (ILT2). Finally, this in vivo experiment was
      able to prove that HLA-G can inhibit the anti-tumor effect of NK cells through
      ILT2. CONCLUSION: The expression of HLA-G was strongly correlated with the
      adverse prognosis of GC. The reason may be that it inhibits the proliferation and
      cytotoxic activity of infiltrating NK cells through ILT2.

PMID- 29224005
TI  - Evidence of Osteoclastic Activity in the Human Temporal Bone.
AB  - Bone remodeling within the otic capsule has been reported to be inhibited
      especially at or near the cochlea, except under some pathological conditions such
      as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur.
      Microcavitations found in periosteal and endosteal layers of human temporal bone
      specimens without otosclerosis, Paget's disease, or inflammation as reported in
      the current study are consistent with osteoclastic bone resorption. Thirty-three
      temporal bones from 33 patients were prepared for light microscopy and classified
      into 4 groups: histologically proven dehiscence of the superior semicircular
      canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90
      years or older and with otosclerosis (n = 10, group 3), and age 90 years or older
      without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic
      locations in the temporal bone in all 4 groups, but not in the cochlea or
      vestibule. Microcavitation within the temporal bone is likely due to osteoclastic
      activity, and it is seen in both young and old patients, patients with and
      without otosclerosis, and in cases with SSCD.

PMID- 29224007
TI  - Coronary Disease Survival with Diabetes.

PMID- 29224006
TI  - Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth
      Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.
AB  - AIMS: The nerve growth factor (NGF) and the vascular endothelial growth factor-A
      (VEGF-A) may be of importance for psychiatric diseases including substance use
      disorders. The aim of the study was to identify differences in the regulation of
      both neuropeptides via the DNA-methylation status of the promotor regions of NGF
      and VEGF-A in different forms of maintenance therapy for opioid dependence and
      the related stress regulation via the hypothalamic-pituitary-adrenal axis.
      METHODS: We compared methylation levels of opioid-dependent patients receiving
      treatment with diamorphine (n = 28) or levomethadone (n = 54) and similar levels
      in a healthy control group (n = 72). RESULTS: There was a significantly higher
      methylation of VEGF-A in opioid-maintained patients with levomethadone compared
      to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003]
      vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting
      up the results in 4 clusters. We found significant changes in methylation rates
      of the opioid-maintained patients compared to the controls in cluster I ([EMM]
      [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133
      [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014]
      vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS: The results are of importance, as
      they indicate that long-term changes in stress regulation regulated by
      neurotrophines are a crucial part of the symptomatology of opioid dependence,
      thus influencing drug consumption and the different forms of opioid-maintenance
      therapies.

PMID- 29224008
TI  - MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells.
AB  - BACKGROUND/AIMS: Glial cell line-derived neurotrophic factor (GDNF) is an
      important factor promoting invasive glioma growth. This study was performed to
      reveal a unique mechanism of glioma cell proliferation and migration. METHODS:
      Human U251 glioma cells were used to screen the optimal GDNF concentration and
      treatment time to stimulate proliferation and migration. MicroRNA (MiRNA)
      expression profiles were detected by microarray and confirmed by real-time
      polymerase chain reaction (PCR). The target genes of differentially expressed
      miRNAs were predicted by miRWalk, and those targeted by multiple miRNAs were
      screened with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway analyses. A regulatory miRNA network was constructed using
      ingenuity pathway analysis (IPA). Target gene expression of differentially
      expressed miRNAs was examined by real-time PCR or mRNA microarray. RESULTS: The
      results show that 50 ng/mL GDNF for 24 h significantly promotes U251 glioma cell
      proliferation and migration (P < 0.05). Seven miRNAs (hsa-miR-194-5p, hsa-miR-152
      3p, hsa-miR-205-5p, hsa-miR-629-5p, hsa-miR-3609, hsa-miR-183-5p, and hsa-miR
      487b-3p) were significantly up-regulated after GDNF treatment (P < 0.05). These
      miRNAs are primarily involved in signal transduction, cell adhesion and cell
      cycle through mitogen-activated protein kinase (MAPK) signaling, focal adhesion
      and glioma signal pathways. Five of these miRNAs (hsa-miR-194-5p, hsa-miR-152-3p,
      hsa-miR-205-5p, hsa-miR-183-5p, and hsa-miR-487b-3p) co-regulate TP53 and Akt.
      mRNA expression levels of four genes co-targeted by two or more up-regulated
      miRNAs were significantly decreased after GDNF treatment (P < 0.05). CONCLUSION:
      GDNF treatment of U251 glioma cells significantly increased the expression of
      seven miRNAs involved in cell adhesion and the cell cycle.

PMID- 29224009
TI  - ITRAQ-Based Proteomics Analysis of Acute Lung Injury Induced by Oleic Acid in
      Mice.
AB  - BACKGROUND/AIMS: This study was conducted to investigate the relationship between
      differentially expressed proteins (DEPs) and the pathogenesis of oleic acid (OA)
      induced acute lung injury (ALI) in mice. METHODS: Eight-week-old male C57BL/6
      mice were injected with OA through the tail vein and sacrificed 6 hours after OA
      administration to identify protein expression levels in lung tissue using
      isobaric tags for relative and absolute quantification (iTRAQ) technology. Then,
      DEPs such as antithrombin III (AT III), 12-lipoxygenase (12-LO), dedicator of
      cytokinesis 2 (DOCK2), polycystin-2 and plasminogen were identified by western
      blotting. Subsequently, we focused on investigating the effect of AT III on
      endothelial integrity using siRNA interference technology. The levels of IL-6, IL
      1beta, TNF-alpha and TGF-beta expression were detected using an enzyme-linked
      immunosorbent assay (ELISA). Alterations in the tight junction component ZO-1 and
      the phosphorylation of myosin light chain (pMLC) were determined by western
      blotting. The stress fiber F-actin were also detected by immunofluorescence
      staining. In addition, endothelial permeability was determined via a transwell
      permeability assay. RESULTS: A total of 5152 proteins were found to be expressed
      in lung tissues from the OA-treated and saline-treated mice. Among these
      proteins, 849 were differentially expressed between the two groups, including 545
      upregulated and 304 downregulated proteins. After AT III knockdown, the levels of
      inflammatory factors and endothelial permeability were elevated, the expression
      of ZO-1 was decreased, and the expression of F-actin and pMLC was increased. All
      these results illustrated that AT III knockdown exaggerated the disruption of
      endothelial integrity mediated by OA. CONCLUSION: These findings using iTRAQ
      technology demonstrate, for the first time, differences in the lung tissue
      expression levels of proteins between OA-treated mice and saline-treated mice.
      This study reveals that 12-LO, DOCK2 and especially AT III may be candidate
      biomarkers for OA-induced acute lung injury.

PMID- 29224010
TI  - MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1.
AB  - BACKGROUND/AIMS: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor
      specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays
      an important role in many types of tumors. However, the roles of DCLK1 in cancer
      and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of
      this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify
      the regulating mechanism of miR-195-DCLK1 in PC cells. METHODS: The expression of
      DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues
      was detected by Western blot and quantitative reverse transcription polymerase
      chain reaction (qRT-PCR), respectively and the correlation between overall
      survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier
      analysis. Bioinformatics tools were used to identify the target gene of miR-195.
      Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were
      analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound
      healing experiments were employed to examine the cellular migration and invasion.
      A xenograft mouse model was also used to test the effects of miR-195 on tumor
      growth and metastasis in vivo. RESULTS: The expression level of DCLK1 and miR-195
      shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level
      is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of
      lymph node metastasis, and poor survival. Luciferase reporter assay shows that
      miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation,
      migration and invasion of PC cells, whereas downregulation of miR-195 has an
      opposite role. These actions were similar to the effects of knockdown and
      overexpression of DCLK1, respectively. CONCLUSIONS: These data suggest that miR
      195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway
      may provide insight into PC progression and represent a novel, promising
      diagnostic and therapeutic target for PC.

PMID- 29224012
TI  - Editorial.

PMID- 29224011
TI  - GLP-1 and Ghrelin Attenuate High Glucose/High Lipid-Induced Apoptosis and
      Senescence of Human Microvascular Endothelial Cells.
AB  - BACKGROUND/AIMS: GLP-1 and ghrelin are common appetite-regulating hormones. Both
      have multiple functions beyond metabolic regulation. However, the effects of GLP
      1 and ghrelin on endothelial biology are not fully understood. Here, we
      investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis
      and senescence. METHODS: Human microvascular endothelial cells (HMECs) were
      exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or
      ghrelin. Cellular apoptosis, senescence, and mitochondrial function were
      measured. In addition, the MAPK and Akt signaling pathways were examined.
      RESULTS: Both GLP-1 and ghrelin treatment decreased the number of TUNEL-positive
      cells and inhibited caspase-3 and PARP cleavage and mitochondrial dysfunction in
      HG/HL-exposed HMECs. GLP-1, but not ghrelin decreased the number of beta
      galactosidase (beta-gal)-positive cells. Furthermore, GLP-1 and ghrelin inhibited
      ERK1/2, JNK1/2, and p38 signaling. GLP-1 suppressed Akt signaling, but ghrelin
      had no effect. Moreover, JNK1/2 and p38 inhibitors, but not ERK1/2 and Akt
      inhibitors, decreased the number of TUNEL-positive cells. Additionally, only the
      Akt inhibitor decreased the number of beta-gal-positive cells. CONCLUSION: These
      results demonstrate that GLP-1 and ghrelin inhibit mitochondrial dysfunction
      under HG/HL conditions, and suppress endothelial apoptosis via inhibiting JNK1/2
      and p38 signaling; moreover, GLP-1 alleviates endothelial senescence via
      inactivating Akt signaling.

PMID- 29224013
TI  - Response of Renal Podocytes to Excessive Hydrostatic Pressure: a Pathophysiologic
      Cascade in a Malignant Hypertension Model.
AB  - BACKGROUND/AIMS: Renal injuries induced by increased intra-glomerular pressure
      coincide with podocyte detachment from the glomerular basement membrane (GBM). In
      previous studies, it was demonstrated that mesangial cells have a crucial role in
      the pathogenesis of malignant hypertension. However, the exact pathophysiological
      cascade responsible for podocyte detachment and its relationship with mesangial
      cells has not been fully elucidated yet and this was the aim of the current
      study. METHODS: Rat renal mesangial or podocytes were exposed to high hydrostatic
      pressure in an in-vitro model of malignant hypertension. The resulted effects on
      podocyte detachment, apoptosis and expression of podocin and integrinbeta1 in
      addition to Angiotensin-II and TGF-beta1 generation were evaluated. To simulate
      the paracrine effect podocytes were placed in mesangial cell media pre-exposed to
      pressure, or in media enriched with Angiotensin-II, TGF-beta1 or receptor
      blockers. RESULTS: High pressure resulted in increased Angiotensin-II levels in
      mesangial and podocyte cells. Angiotensin-II via the AT1 receptors reduced
      podocin expression and integrinbeta1, culminating in detachment of both viable
      and apoptotic podocytes. Mesangial cells exposed to pressure had a greater
      increase in Angiotensin-II than pressure-exposed podocytes. The massively
      increased concentration of Angiotensin-II by mesangial cells, together with
      increased TGF-beta1 production, resulted in increased apoptosis and detachment of
      non-viable apoptotic podocytes. Unlike the direct effect of pressure on
      podocytes, the mesangial mediated effects were not related to changes in adhesion
      proteins expression. CONCLUSIONS: Hypertension induces podocyte detachment by
      autocrine and paracrine effects. In a direct response to pressure, podocytes
      increase Angiotensin-II levels. This leads, via AT1 receptors, to structural
      changes in adhesion proteins, culminating in viable podocyte detachment.
      Paracrine effects of hypertension, mediated by mesangial cells, lead to higher
      levels of both Angiotensin-II and TGF-beta1, culminating in apoptosis and
      detachment of non-viable podocytes.

PMID- 29224014
TI  - Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy for Upper Tract
      Urothelial Carcinoma Increased the Risk of Intravesical Recurrence.
AB  - OBJECTIVE: To assess the impact of diagnostic ureteroscopy (URS) prior to radical
      nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper
      tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A systematic literature
      search of the Medline, Embase, PubMed, and Cochrane library was performed in
      August 2017. Cumulative analyses of available hazard ratios (HRs) and their 95%
      CI were conducted using Stata version 12.0. RESULTS: Eleven studies including
      4,057 participants were included, with a total of 1,403 patients diagnosed with
      IVR during the follow-up period. The pooled HRs of eight studies suggested that
      diagnostic URS prior to RNU significantly increased the IVR risk after RNU (HR
      1.53, 95% CI 1.31-1.77; p < 0.001). However, the preoperative diagnostic URS was
      not associated with cancer-specific survival (HR 0.72; p = 0.11), metastasis-free
      survival (HR 1.09; p = 0.60) or overall survival (HR 1.12; p = 0.73). No
      publication bias was observed (Begg, p = 0.90; Egger, p = 0.71). CONCLUSIONS:
      Regardless, the diagnostic URS prior to RNU might increase the IVR risk in
      patients with UTUC. As ureteroscopy provides important prognostic and therapeutic
      value and guides decisions in UTUC, more future studies should be performed to
      find a novel way to mitigate the potential risk of IVR after RNU, such as
      chemoprophylaxis after endoscopy.

PMID- 29224015
TI  - Renal Resistive Index as a Novel Indicator for Renal Complications in High-Fat
      Diet-Fed Mice.
AB  - BACKGROUND/AIMS: The renal resistive index (RI) is a novel candidate as a renal
      injury prognostic indicator, but it remains unclear how renal RI levels
      correspond to renal injury in diabetic nephropathy. METHODS: To examine this
      issue, we compared 8-week-old male C57BL/6 mice fed with high-fat diet (HFD)
      versus chow diet (CHD) for 16 weeks. At 8 and 12 weeks, the glomerular filtration
      rate (GFR), urinary albumin-to-creatinine ratio (UACR), and inflammatory factors
      (IL-1beta, IL-6, TNFalpha, and MCP-1) were measured, along with the increase in
      renal RI. RESULTS: Our study suggests RI values positively correlate with GFR for
      the first 12 weeks of HFD feeding. In contrast, the GFR of 16-week HFD feeding is
      lower than that of 12-week HFD feeding, whereas RI levels are significantly
      increased. Additionally, our study suggests RI values accurately indicate the
      renal fibrosis and renal injury in HFD-fed mice treated with lovastatin.
      CONCLUSION: This study seems to confirm the utility of a noninvasive and
      repeatable ultrasound parameter to rapidly evaluate renal fibrosis in a HFD
      induced type 2 diabetic mouse model in vivo. This highly sensitive and comparable
      renal RI measurement could monitor the whole procedure of disease development in
      real-time. RI measurement of the renal artery is capable of differentiating
      responses to standard therapy with lovastatin in HFD-fed mice from the CHD group.

PMID- 29224016
TI  - Survival in Type 1 and Type 2 Diabetes in a Population Referred for Invasive
      Evaluation of Coronary Disease.
AB  - OBJECTIVES: To evaluate long-term and time trends of survival in patients with a
      clinical diagnosis of type 1 and type 2 diabetes compared to patients without
      diabetes in a population referred for invasive treatment of coronary disease.
      METHODS: Patients examined for heart disease at the Feiring LHL Clinics from
      March 1999 until December 2014 were followed for survival until 20 September,
      2015. This yielded 43,872 patients with a known survival status including 1,326
      (3.0%) patients with type 1 diabetes and 4,564 (10.9%) with type 2 diabetes.
      RESULTS: Cox regression revealed a hazard ratio (HR) in type 1 and type 2
      diabetes, respectively, of 1.78 (95% confidence interval [CI] 1.60-1.99) and 1.29
      (95% CI 1.21-1.37). Comparing survival in the treatment periods before and after
      2007, patients without diabetes and with type 2 diabetes had a reduced HR of 0.78
      (95% CI 0.72-0.84) and 0.76 (95% CI 0.63-0.91), respectively, but there was no
      reduction in type 1 diabetes (HR 1.03; 95% CI 0.74-1.42). CONCLUSIONS: Type 1 and
      type 2 diabetes have excess long-term mortality. In the nondiabetic and type 2
      diabetic patients, a reduction in mortality has been noted in recent years, but
      has not been observed in type 1 diabetic patients.

PMID- 29224017
TI  - The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury
      Through Expansion of Regulatory T Cells.
AB  - BACKGROUND/AIMS: Regulatory T cells (Tregs) can suppress immunologic damage in
      myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex
      vivo expansion of these cells for clinical application remains challenging. Here,
      we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg
      expansion, can attenuate MIRI in mice. METHODS: Myocardial I/R was surgically
      induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1)
      sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab
      complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8)
      IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-beta1 mAbs, 11) IL-2C+anti
      IL-10 mAbs. The following parameters were measured at different time points:
      infarct area, myocardial apoptosis, splenocytes, the inhibitory function of
      Tregs, and presence of inflammatory factors. In addition, immunohistochemistry
      analysis was performed. RESULTS: We observed that Tregs were activated in
      response to MIRI. IL-2C administered before MIRI induced Treg expansion in both
      spleen and heart, attenuated Th1 and Th17 cell numbers, improved myocardial
      function, and attenuated both infiltration of inflammatory cells and apoptosis
      after MIRI. Furthermore, IL-2C administration reduced expression of inflammatory
      cytokines in the heart and attenuated proliferation of splenic cells. Depletion
      of Tregs with anti-CD25 mAb abrogated the beneficial effects of IL-2C. However,
      IL-2C-mediated myocardial protection was not dependent on either IL-10 or TGF
      beta. In addition, IL-2C administration after MIRI did not reduce infarct area,
      but did improve myocardial function slightly and reduced myocardial fibrosis.
      CONCLUSION: Our results demonstrate that IL-2C-induced Treg expansion attenuates
      MIRI and improves myocardial recovery in vivo, suggesting that IL-2C is a
      promising therapeutic target for myocardial IRI.

PMID- 29224018
TI  - Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in
      a Rat Model.
AB  - BACKGROUND/AIMS: To explore the effect of sulforaphane (SFN) treatment in rats
      through the induction of Stress Urinary Incontinence (SUI) via the Nrf2-ARE
      pathway. METHODS: A total of 18 female rats (Sprague-Dawley) were assigned to
      three groups: a control group, an SUI group, and an SUI+SFN group (six rats per
      group). Rats in the treatment groups were induced via postpartum vaginal balloon
      dilation and bilateral ovariectomy. Rats in the SUI+SFN group were treated via
      intraperitoneal injection once per day for a total of one month. Urethral
      sphincter muscle histological was observed by HE and Masson staining. Peak
      voiding pressure and interval of micturition were measured by cystometry.
      Oxidative stress markers and protein expression in the Nrf2-ARE pathway were
      examined by immunohistochemical staining and western blotting. RESULTS: Prolonged
      micturition interval and higher peak voiding pressure were observed in the
      SUI+SFN group. Disturbance of muscle morphology was ameliorated, muscle content
      was elevated, and collagen content was restrained in response to SFN treatment.
      The SOD, GSH-Px, and CAT activities were elevated in the SUI+SFN group compared
      to those in the control group. The level of cell apoptosis was decreased in SUI
      rats after SFN treatment; however, apoptosis was mainly located in the urethral
      mucosa instead of the muscle layer. SFN reduced the Bax/Bcl-2 expression ratio.
      Nrf2 and Nrf2 target antioxidant proteins were elevated in the SFN group.
      CONCLUSIONS: SFN was effective for SUI treatment via decreasing oxidative stress
      and activating the Nrf2-ARE pathway.

PMID- 29224019
TI  - The MiR-495/Annexin A3/P53 Axis Inhibits the Invasion and EMT of Colorectal
      Cancer Cells.
AB  - BACKGROUND/AIMS: More and more reports have shown that the dysregulation of
      miRNAs can contribute to the progression and metastasis of human cancers. Many
      studies have shown that the down-regulation of the miR-495 level occurs in a
      variety of cancers, including colorectal cancer (CRC). However, the precise
      molecular mechanisms of miR-495 in CRC have not been well clarified. In the
      current study, we investigated the biological functions and molecular mechanisms
      of miR-495 in CRC cell lines. METHODS: qRT-PCR was used to determine the level of
      miR-495 in CRC cell lines and tissues. A miR-495 mimic and inhibitor were
      transfected into CRC cells, and the effects of miR-495 on the invasion and EMT
      were explored by qRT-PCR as well as transwell and Western blot assays. Meanwhile,
      luciferase assays were performed to validate Annexin A3 as a miR-495 target in
      CRC cells. RESULTS: In our study, we found that miR-495 is down-regulated in CRC
      tissues and cell lines. Moreover, the low level of miR-495 was associated with
      increased expression of Annexin A3 in CRC tissues and cell lines. The invasion
      and EMT of CRC cells were suppressed by the overexpression of miR-495. However,
      the down-regulation of miR-495 promoted the invasion and EMT of CRC cells.
      Bioinformatics analysis predicted that Annexin A3 was a potential target gene of
      miR-495. Next, the luciferase reporter assay confirmed that miR-495 could
      directly target Annexin A3. Consistent with the effect of miR-495, the down
      regulation of Annexin A3 by siRNA inhibited the invasion and EMT of CRC cells
      through the up-regulation of p53. The introduction of Annexin A3 in CRC cells
      partially blocked the effects of the miR-495 mimic. CONCLUSION: The introduction
      of miR-495 directly targeted Annexin A3 to inhibit the invasion and EMT of CRC
      cells by up-regulating p53, and the down-regulation of Annexin A3 was essential
      for inhibiting the invasion and EMT of CRC cells by overexpressing miR-495.
      Overall, the re-activation of the miR-495/Annexin A3/ p53 axis may represent a
      new strategy for overcoming metastasis of CRC.

PMID- 29224020
TI  - Association Between GLCCI1 Promoter Polymorphism (Rs37972) and Post-Transplant
      Hypertension in Renal Transplant Recipients.
AB  - BACKGROUND/AIMS: Post-transplant hypertension is highly prevalent in renal
      transplant recipients and is a risk factor for graft loss, cardiovascular disease
      and death. Glucocorticoid is used to prevent rejection, but simultaneously
      increases the risk of post-transplant hypertension. The glucocorticoid-induced
      transcript 1 (GLCCI1) promoter polymorphism (rs37972) has been reported to be
      associated with response to glucocorticoid therapy in asthma. We therefore
      examined the association between GLCCI1 promoter polymorphism and post-transplant
      hypertension in renal transplant recipients. METHODS: We conducted a
      retrospective cohort study of renal transplantation at a single university
      hospital from October 2003 to January 2014. Fifty consecutive adult recipients
      were analyzed, with clinical data retrieved from a prospectively collected
      database. Genotyping was carried out using genomic DNA derived from recipient's
      blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively
      analyzed by immunohistochemical staining of recipients' native kidney biopsy
      specimens. The primary outcome measure was post-transplant hypertension. RESULTS:
      Post-transplant hypertension was observed in 14/17 (82%) of recipients with CC,
      18/20 (90%) with CT, and 2/13 (15%) with TT genotype. CC/CT genotype was
      significantly associated with post-transplant hypertension, even after adjustment
      for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P =
      0.026). In addition, we observed that GLCCI1 immunoreactivity in arteriolar
      endothelial cells was higher in kidney specimens obtained from recipients with a
      CC/CT genotype than a TT genotype (P = 0.021). CONCLUSION: GLCCI1 promoter
      polymorphism rs37972 may be associated with post-transplant hypertension.

PMID- 29224022
TI  - Bladder Fetal Rhabdomyoma Intermediate Type.
AB  - INTRODUCTION: Rhabdomyomas are benign tumors of striated muscle, the bladder
      localization is very rare. CLINICAL CASE: We present an 87-year-old male
      consulting for gross hematuria. Cystoscopy was done with evidence of bulged
      bladder mucosa in right side wall and dome. Post-transurethral resection of the
      bladder (TURB) pathological anatomy was negative for malignancy. As extension
      study abdominopelvic computed tomography was performed identifying a bladder
      thickening of right posterior sidewall and an increased density of the adjacent
      fat. Second TURB was performed and a fetal bladder rhabdomyoma intermediate type
      was obtained. We performed another biopsy to confirm this rare pathology, with
      the same diagnosis. Subsequently, the patient continues with hematuria deciding
      on hemostatic radiotherapy (not candidate for cystectomy or arterial
      embolization). Currently, the patient is asymptomatic. DISCUSSION: Bladder
      rhabdomyomas are rare tumors, and, in fact, there have been only 5 papers
      published. Some cases are only isolation cited in the bladder mesenchymal tumors,
      and other polemic cases in which clinical and macroscopic characteristics
      remembered a rhabdomyosarcoma. The importance of this publication case is the
      macro- and microscopic images that can corroborate the final diagnosis, helping
      us to differentiate between rhabdomyoma, rhabdomyofibroma, or the malignant
      rhabdomyosarcoma, and shows the treatment possibilities of these tumors.

PMID- 29224021
TI  - Comparison of Muscle Mass Indices Using Computed Tomography or Dual X-Ray
      Absorptiometry for Predicting Physical Performance in Hemodialysis Patients.
AB  - BACKGROUND/AIMS: Our study aims to evaluate the association between thigh muscle
      cross-sectional area (TMA) using computed tomography (CT), or appendicular
      skeletal muscle mass (ASM) using dual energy X-ray absorptiometry (DEXA), and
      physical performance levels in hemodialysis (HD) patients. METHODS: Patients were
      included if they were on HD for >=6 months (n = 84). ASM and TMA were adjusted to
      body weight (BW, kg) or height2 (Ht2, m2). Each participant performed a short
      physical performance battery test (SPPB), a sit-to-stand for 30 second test
      (STS30), a 6-minute walk test (6-MWT), a timed up and go test (TUG), and hand
      grip strength (HGS) test. RESULTS: Correlation coefficients for SPPB, GS, 5STS,
      STS30, 6-MWT, and TUG were highest in TMA/BW. Results from partial correlation or
      linear regression analyses displayed similar trends to those derived from
      Pearson's correlation analyses. An increase in TMA/BW or TMA/Ht2 was associated
      with a decreased odds ratio of low SPPB, GS, or HGS in multivariate analyses.
      Indices using DEXA were associated with a decreased odds ratio of a low HGS only
      in multivariate analysis. CONCLUSION: TMA indices using CT may be more valuable
      in predicting physical performance or strength in HD patients.

PMID- 29224023
TI  - Negative Symptoms and Avoidance of Social Interaction: A Study of Non-Verbal
      Behaviour.
AB  - BACKGROUND: Non-verbal behaviour is fundamental to social interaction. Patients
      with schizophrenia display an expressivity deficit of non-verbal behaviour,
      exhibiting behaviour that differs from both healthy subjects and patients with
      different psychiatric diagnoses. The present study aimed to explore the
      association between non-verbal behaviour and symptom domains, overcoming
      methodological shortcomings of previous studies. SAMPLING AND METHODS:
      Standardised interviews with 63 outpatients diagnosed with schizophrenia were
      videotaped. Symptoms were assessed using the Clinical Assessment Interview for
      Negative Symptoms (CAINS), the Positive and Negative Syndrome Scale (PANSS) and
      the Calgary Depression Scale. Independent raters later analysed the videos for
      non-verbal behaviour, using a modified version of the Ethological Coding System
      for Interviews (ECSI). RESULTS: Patients with a higher level of negative symptoms
      displayed significantly fewer prosocial (e.g., nodding and smiling), gesture, and
      displacement behaviours (e.g., fumbling), but significantly more flight
      behaviours (e.g., looking away, freezing). No gender differences were found, and
      these associations held true when adjusted for antipsychotic medication dosage.
      CONCLUSIONS: Negative symptoms are associated with both a lower level of actively
      engaging non-verbal behaviour and an increased active avoidance of social
      contact. Future research should aim to identify the mechanisms behind flight
      behaviour, with implications for the development of treatments to improve social
      functioning.

PMID- 29224024
TI  - Association of the TG/HDL-C and Non-HDL-C/HDL-C Ratios with Chronic Kidney
      Disease in an Adult Chinese Population.
AB  - BACKGROUND/AIMS: Evidence indicates a role for dyslipidemia in the development of
      chronic kidney disease (CKD). However, the association of lipid abnormalities and
      their ratios with kidney disease using the new CKD Epidemiology Collaboration
      (CKD-EPI) equation is not well understood. METHODS: This cross-sectional study
      included 48,054 adult subjects. CKD was defined as an estimated glomerular
      filtration rate <60 ml/min/1.73 m2 or dipstick-positive proteinuria. Logistic
      regression models were used to examine the relationship between lipid variables
      and CKD. RESULTS: The prevalence of CKD in this study was 3.7%. When the
      participants exhibited higher serum triglyceride (TG), a higher TG/high-density
      lipoprotein cholesterol (TG/HDL-c) ratio or a higher non-HDL-c/HDL-c ratio or HDL
      c in a lower quartile, the prevalence of CKD tended to be higher. The
      multivariate adjusted odds ratios for CKD per 1 standard deviation increase in
      lipid level were 1.17 (1.10-1.23) for TG, 0.86 (0.79-0.93) for HDL-c, 1.21 (1.13
      1.31) for the TG/HDL-c ratio, and 1.14 (1.06-1.22) for the non-HDL-c/HDL-c ratio.
      No significant association was detected between CKD and total cholesterol (TC),
      non-HDL-c or the low-density lipoprotein cholesterol/HDL-c (LDL-c/HDL-c) ratio.
      CONCLUSION: In this relatively healthy adult Chinese population, the CKD-EPI
      equation determined that the TG/HDL-c and non-HDL-c/HDL-c ratios as well as TG
      and HDL-c correlate with the prevalence of CKD.

PMID- 29224025
TI  - Alterations in Adiposity and Glucose Homeostasis in Adult Gasp-1 Overexpressing
      Mice.
AB  - BACKGROUND/AIMS: Myostatin is known as a powerful negative regulator of muscle
      growth playing a key role in skeletal muscle homeostasis. Recent studies revealed
      that myostatin-deficient mice lead to an increase of insulin sensitivity, a
      decrease of adiposity and a resistance to obesity, showing that myostatin can
      also impact on metabolism. Thus, myostatin appeared as a potential therapeutic
      target to treat insulin resistance. METHODS: We generated transgenic mice
      overexpressing Gasp-1, a myostatin inhibitor. RESULTS: Surprisingly, we found
      that these mice gained weight with age due to an increase in fat mass associated
      with ectopic fat accumulation. In addition, these mice developed an adipocyte
      hypertrophy, hyperglycemia, hyperinsulinemia, muscle and hepatic insulin
      resistance. Understanding the molecular networks controlling this insulin
      resistance responsiveness in overexpressing Gasp-1 mice is essential. Molecular
      analyses revealed a deregulation of adipokines and muscle cytokines expression,
      but also an increase in plasma myostatin levels. The increase in myostatin
      bioactivity by a positive feedback mechanism in the Tg(Gasp-1) transgenic mice
      could lead to this combination of phenotypes. CONCLUSION: Altogether, these data
      suggested that overexpressing Gasp-1 mice develop most of the symptoms associated
      with metabolic syndrome and could be a relevant model for the study of obesity or
      type 2 diabetes.

PMID- 29224026
TI  - Heminephrectomy in Adults: A Systematic Review with Cumulative Analysis.
AB  - INTRODUCTION: Duplex collecting system of the kidney is a relatively common
      abnormality, with the majority of symptomatic cases discovered in childhood.
      Treatment is commonly a heminephrectomy of the affected moiety. We aimed to
      conduct a systematic review of the literature to provide the best available
      evidence for heminephrectomy for duplex kidneys in the adult population.
      MATERIALS AND METHODS: A literature search was conducted in September 2017 with
      no limitations being placed on language, region, date or publication type. Data
      were represented numerically and analysed cumulatively. RESULTS: Seven
      retrospective studies with 66 patients were included. Of which, 56/66 operations
      were performed laparoscopically, 5/66 were robot-assisted and 5/66 were open
      procedures. Complete resolution of symptoms was reported in 53/55 (96.4%) of
      patients in five studies providing outcome data. Of the 6 studies reporting
      complications, there were a total of 9 complications (9/62, 14.5%), however 5 of
      these were found to be in one study alone. CONCLUSIONS: This review emphasises
      the scarcity of evidence for heminephrectomy in adults. Nonetheless, it has been
      shown that this operation may be effective in alleviating patients' symptoms in
      addition to being safe in experienced hands.

PMID- 29224029
TI  - Lasers, Lights, and Energy Devices: State of the Art; Introduction.

PMID- 29224028
TI  - ATP Binding Cassette Subfamily A Member 2 (ABCA2) Expression and Methylation are
      Associated with Alzheimer's Disease.
AB  - BACKGROUND ABCA2 has been genetically linked to Alzheimer's disease (AD) risk,
      but its mRNA expression and epigenetics in AD have not been investigated.
      MATERIAL AND METHODS To explore the diagnosis value of ABCA2 mRNA expression in
      AD, 2 datasets GES15222 and GSE33000 containing expression profile of brain
      cortex tissues and 2 datasets GSE63063 (Cohort 1) and GSE63063 (Cohort 2)
      containing expression profile of blood were downloaded from the NCBI GEO database
      and analyzed by receiver operating characteristic curve (ROC) analyses and
      logistic regression. The ABCA2 co-expressed genes were also analyzed by GO
      annotation to investigate the potential molecular mechanisms. RESULTS The
      analyses results suggested ABCA2 mRNA expression was upregulated significantly in
      AD compared with controls in all datasets. ROC analysis suggested that ABCA2 was
      associated with AD in all datasets, which were also proved by univariate and
      multivariate analyses. Next, the dataset GSE80970 containing methylation profiles
      of prefrontal cortex tissues from AD patients were downloaded and analyzed.
      Methylation of 2 of 36 CpG islands in ABCA2 gene with high diagnostic accuracy of
      AD from controls in ROC analyses were found to be negatively associated with AD
      risk in univariate analysis. One was still associated with AD risk after
      adjustment of confounding factors. Additional analyses indicated that ACBA2 mRNA
      expression could be used to diagnose mild cognitive impairment (MCI) and
      Huntington's disease (HD) from controls and to distinguish HD from AD, but not AD
      from MCI. Furthermore, the genes involved in AD during ABCA2 alteration were
      analyzed by GO analysis. CONCLUSIONS ABCA2 mRNA expression and methylation is
      associated AD risk. ABCA2 may be used as a biomarker for AD diagnosis and may be
      a potential therapeutic target of AD.

PMID- 29224027
TI  - A Clinical Scoring System for Diagnosis of Ocular Demodicosis.
AB  - BACKGROUND Demodex may cause chronic and refractory blepharitis with associated
      ocular surface problems, and its diagnosis and treatment can be quite
      challenging. In this study, our aim was to assess the efficacy of tea tree oil in
      Demodex treatment on caucasian patients in an industrialized region of Turkey,
      and to develop a systematic scoring system for extremely accurate diagnosis in
      the absence of advanced facilities. MATERIAL AND METHODS Charts of 412 patients
      with blepharitis were reviewed. A group of 39 out of 412 cases were identified as
      chronic and treatment-refractory, and therefore were enrolled in this study.
      Eyelashes from each of the lower and upper eyelids of both eyes were evaluated at
      *40 and *100 magnification using light microscopy. Treatment was started with 4%
      tea tree oil eyelid gel and 10% eyelash shampoo. Symptoms and findings were
      scored according to the most common complaints. RESULTS The mean age of the
      patients was 54.1+/-15.4 years. Seventeen (43.5%) patients were male and 22
      (56.5%) patients were female. In 30 out of the 39 patients (76.9%) D.
      folliculorum was detected. Symptoms disappeared in 25 patients. The mean score of
      patients who were Demodex-negative was 2.7+/-1.0, and the mean score of patients
      who were Demodex-positive was 3.8+/-1.6 (p=0.047). Ninety-four percent of those
      with a score of 4 and over were found to be Demodex-positive (p=0.025).
      CONCLUSIONS Treatment with tea tree oil can be successful. If there is no
      facility to identify Demodex under light microscopy, we recommend starting
      treatment for patients who have scores of 4 and over using the scoring chart
      developed in this study.

PMID- 29224030
TI  - Advances in fractional technology for skin rejuvenation, skin tightening, drug
      delivery, and treating scars and skin defects.
AB  - The development of fractional photothermolysis has revolutionized the treatment
      of skin scarring, rejuvenation, and tightening. By creating targeted microthermal
      zones and leaving surrounding tissue intact, this concept has provided the field
      with efficacious results, with less downtime and a better safety profile. This
      has started to change the paradigm of what is considered first-line treatment for
      scarring and rejuvenation. While originally applied to nonablative lasers,
      fractionation has now been employed in ablative, quality-switched, picosecond,
      and novel hybrid fractional lasers. Furthermore, other energy-based technologies,
      such as radiofrequency, have adopted the concept of fractionation in an attempt
      to optimize the balance of efficacy, downtime, and side effects. Herein, we
      describe how the ever-expanding repertoire of fractional devices is applied to
      the treatment of scarring, skin rejuvenation, and tightening. In addition, newer
      applications, such as transdermal drug delivery, are being developed by using
      fractional devices. Growing experience with these devices has broadened their
      relevance to more skin types and body sites than ever. Ultimately, the knowledge
      of appropriate treatment parameters is paramount and allows for the safe and
      effective treatment of a variety of patients with numerous devices.

PMID- 29224031
TI  - Short-pulsed laser for the treatment of tattoos, pigmented lesions, scars and
      rejuvenation.
AB  - This review describes the use of picosecond lasers for the treatment of tattoos,
      pigmented lesions, scars, and their use in rejuvenation. These devices have
      delivered enhanced efficacy for the treatment of tattoos and pigmented lesions
      when compared to the older 40-50 nanosecond devices. The fractional delivery with
      the picosecond devices have opened up a new method of rejuvenation for
      photodamaged skin and the treatment of scars. The delivery of these high-energy
      short pulses have created zones of injury in the skin referred to as areas of
      laser-induced optical breakdown. These areas of damage appear to produce
      cytokines and chemokines which result in epidermal and dermal repair and
      remodeling. The dual use of these devices with the flat and the fractional optics
      have made these devices useful in many ways that have been unanticipated.

PMID- 29224032
TI  - Microneedling: a new approach for treating textural abnormalities and scars.
AB  - Microneedling is a minimally invasive procedure wherein small holes are created
      across the stratum corneum while keeping the epidermis partially intact. This
      produces microchannels that increase skin permeability and simultaneously
      stimulate growth factor release. Since the epidermis is retained, microneedling
      has less risk of infection, postinflammatory hyperpigmentation, and scarring
      compared to other resurfacing modalities. This is a review of the literature on
      microneedling in the treatment of textural abnormalities, specifically rhytides,
      scars, and striae.

PMID- 29224033
TI  - Noninvasive approach to treatment of submental fullness.
AB  - A recent survey done by the American Society for Dermatologic Surgery indicated
      that 67% of respondents were bothered by "excess fat under the chin/neck."
      Accumulation of fat in the preplatysmal compartment of the neck is a common cause
      for fullness in the submental area. In the past, surgical liposuction was the
      only option to remove fat in the submental area. Although effective, liposuction
      does have risks and downtime. Recently, noninvasive options for treatment of
      submental fat have been introduced. These include treatment with deoxycholic
      acid, known as Kybella(r), and cryolipolysis using the CoolMiniTM handpiece. Both
      of these treatments offer less downtime fewer potential risks than the surgical
      counterpart. This article summarizes these two procedures and describes
      noninvasive approaches to treatment of submental fat.

PMID- 29224034
TI  - Noninvasive body contouring.
AB  - In a society where stigma surrounds cosmetic procedures and yet a thin and
      sculpted physique is idealized, noninvasive body contouring satisfies the demand
      to reduce excess and undesired body fat in areas that persist despite exercise
      and diet. Numerous devices are available to meet this need; however, choosing the
      "perfect" device is challenging because the science and data are often limited
      with variable results. In this paper, we review 7 US Food and Drug Administration
      approved noninvasive body contouring therapies in hopes of providing some clarity
      to this area.

PMID- 29224035
TI  - Cellulite: a review of pathogenesis-directed therapy.
AB  - Cellulite is a condition that affects the majority of postpubertal women and can
      negatively impact quality of life. This review discusses several proposed
      pathophysiologies of cellulite, and examines treatment options that have been
      utilized, focusing on the etiologic factor targeted by the therapies. This
      approach aims to help clarify the pathogenesis of cellulite and provide a road
      map for developing effective treatment paradigms for patients.

PMID- 29224036
TI  - Laser advances in the treatment of burn and traumatic scars.
AB  - The realm of scar management is constantly changing. Many factors need to be
      considered when developing a comprehensive treatment plan, including the nature
      of the scar and the patient. Scar characteristics can be divided by color, scar
      type and thickness, and body location. Topical and intralesional agents and light
      and laserbased treatments can be used to revitalize and restore damaged skin in
      atrophic and hypertrophic scars. The most commonly used lasers are the pulsed-dye
      laser (PDL) and fractional lasers. Ideally, a combination approach using topical
      and intralesional medications along with pulsed-dye laser and a fractional laser
      should be considered in all patients wishing to undergo treatment of their
      hypertrophic and atrophic scars. Keloidal scars tend to be resistant to standard
      therapy so other modalities should be considered.

PMID- 29224037
TI  - Opportunities for laser-assisted drug delivery in the treatment of cutaneous
      disorders.
AB  - Fractional laser-assisted drug delivery (LADD) is increasingly finding its way
      into clinical practice as a new means to enhance topical drug uptake and improve
      treatment of cutaneous disorders. To date, LADD has been used for a wide range of
      conditions, including photodamaged skin, neoplastic lesions, scars, cutaneous
      infections, and vitiligo as well as for topical anesthetic and aesthetic
      procedures. Substantiated by randomized controlled clinical trials, strong
      evidence is available for LADD's usefulness for photodynamic therapy (PDT), for
      which improved efficacy using laser-assisted photosensitizer treatment is
      established for actinic keratosis compared with conventional PDT. Over time, the
      modality has undergone increasing refinement and offers the potential advantages
      of reduced treatment durations, shortened incubation times, and the replacement
      of cumbersome, patient-dependent treatment regimens with quick, in-office
      procedures. Notwithstanding, LADD is still a new enhancement technique, and risks
      of both local and systemic adverse events are insufficiently explored. With
      conscientious development, however, LADD promises to improve existing regimens
      and make new pharmacological treatments a reality for a wide range of cutaneous
      disorders.

PMID- 29224038
TI  - Skin tightening-does it really exist?
AB  - Skin tightening is one of the cornerstones of skin rejuvenation and is defined as
      the improvement of skin laxity and crepiness of the skin. There are several
      energy-based devices that can produce significant skin tightening without
      surgery, both on and off the face. The mechanisms of skin tightening involve
      collagen denaturation resulting in collagen shrinkage and tissue tightening, and
      the wound healing response that generates new collagen and elastin. These
      hypothesized mechanisms of skin contraction leading to clinical skin tightening
      have been derived from histological, immunohistochemical, and electron microscope
      analysis, as well as in vitro and in vivo experiments. This review is aimed at
      evaluating and analyzing the literature on the proposed mechanisms for skin
      tightening by minimally invasive energy-based technologies.

PMID- 29224039
TI  - State-of-the-art lasers and light treatments for vascular lesions: from red faces
      to vascular malformations.
AB  - Notable milestones in the treatment of vascular lesions have been achieved over
      the past century. Many cutaneous vascular lesions can be successfully treated
      with lightbased devices. In this review, we will discuss the treatment of port
      wine birthmarks, lymphatic malformations, infantile hemangiomas, rosacea, venous
      lakes, pyogenic granulomas, cherry angiomas, and angiofibromas using lasers,
      total reflection amplification of spontaneous emission of radiation, intense
      pulsed light, and photodynamic therapy. In addition, for several of these
      diagnoses, we will review medical therapies that can be combined with light-based
      devices to provide enhanced results.

PMID- 29224040
TI  - Treatment of auditory hallucinations with bilateral theta burst stimulation
      (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter
      trial.
AB  - : Auditory verbal hallucinations (AH) are core symptoms of schizophrenia. They
      are often severely distressing and refractory to therapy. Their perception is
      associated with increased activity in temporoparietal areas of the brain.
      Repetitive transcranial magnetic stimulation (rTMS) can reduce focal brain
      hyperactivity and has been shown to ameliorate AH. However, controlled
      multicenter clinical trials are still missing, effect sizes are moderate, and the
      treatment with rTMS is time consuming. Continuous theta burst stimulation (cTBS)
      is a quicker and potentially more effective technique to reduce cortical
      hyperactivity. First case and pilot studies indicate effectiveness in the
      treatment of AH. In this randomized, sham-controlled, double-blind multicenter
      clinical trial, 86 patients with schizophrenia spectrum disorder will be
      randomized to either cTBS or sham to the left and right temporoparietal cortex
      during three consecutive weeks (15 sessions totally). In each session, both
      hemispheres will be stimulated sequentially. The order in the first session (left
      right or right-left, respectively) will be determined by randomization and
      alternated in all following sessions. Primary outcome is the reduction of mean
      PSYRATS-AH score after cTBS as compared to sham treatment. Follow-up measurements
      will be performed 1, 3 and 6 months after the end of the treatment. Statistical
      analysis will be based on the intention-to-treat population including all
      randomized patients using an analysis of covariance. This multicenter-controlled
      clinical trial will be able to provide decisive evidence for the efficacy of cTBS
      in the treatment of AH. The results will be suitable to clarify the role of this
      innovative, pathophysiology-based therapeutic approach in treatment guidelines
      for AH. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT02670291.

PMID- 29224041
TI  - Identifying and monitoring neurons that undergo metamorphosis-regulated cell
      death (metamorphoptosis) by a neuron-specific caspase sensor (Casor) in
      Drosophila melanogaster.
AB  - Activation of caspases is an essential step toward initiating apoptotic cell
      death. During metamorphosis of Drosophila melanogaster, many larval neurons are
      programmed for elimination to establish an adult central nervous system (CNS) as
      well as peripheral nervous system (PNS). However, their neuronal functions have
      remained mostly unknown due to the lack of proper tools to identify them. To
      obtain detailed information about the neurochemical phenotypes of the doomed
      larval neurons and their timing of death, we generated a new GFP-based caspase
      sensor (Casor) that is designed to change its subcellular position from the cell
      membrane to the nucleus following proteolytic cleavage by active caspases.
      Ectopic expression of Casor in vCrz and bursicon, two different peptidergic
      neuronal groups that had been well-characterized for their metamorphic programmed
      cell death, showed clear nuclear translocation of Casor in a caspase-dependent
      manner before their death. We found similar events in some cholinergic neurons
      from both CNS and PNS. Moreover, Casor also reported significant caspase
      activities in the ventral and dorsal common excitatory larval motoneurons shortly
      after puparium formation. These motoneurons were previously unknown for their
      apoptotic fate. Unlike the events seen in the neurons, expression of Casor in non
      neuronal cell types, such as glial cells and S2 cells, resulted in the formation
      of cytoplasmic aggregates, preventing its use as a caspase sensor in these cell
      types. Nonetheless, our results support Casor as a valuable molecular tool not
      only for identifying novel groups of neurons that become caspase-active during
      metamorphosis but also for monitoring developmental timing and cytological
      changes within the dying neurons.

PMID- 29224042
TI  - Association between continuous positive airway pressure and serum
      aminotransferases in patients with obstructive sleep apnea.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) has been suggested to be a potential
      contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the
      association between continuous positive airway pressure (CPAP) and NAFLD in OSA
      patients are limited and controversial. OBJECTIVES: The aim of this study was to
      assess the relationship between OSA and NAFLD and the effect of CPAP therapy on
      serum aminotransferase levels in OSA patients. METHODS: A total of 160
      consecutive patients who underwent standard polysomnography were enrolled. Blood
      samples were obtained in the morning after sleep for biological profile
      measurements. Non-invasive ultrasound techniques were used to assess liver
      steatosis and fibrosis. Within the OSA group, serum aminotransferases were
      detected before and after CPAP treatment. RESULTS: Alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver
      steatosis score increased significantly with an increase in OSA severity.
      Stepwise multiple regression with liver steatosis score, ALT, AST as dependent
      variable, respectively, apnea-hypopnea index (beta = 0.447, p = 0.020; beta =
      0.266, p = 0.001; beta = 0.351, p = 0.020, respectively) significantly predicted
      the liver steatosis score, ALT, AST after adjustment for confounders. After 3
      months of CPAP treatment, there was a significant decrease in both ALT (54.20 +/-
      24.34 vs. 46.52 +/- 24.95, p = 0.000) and AST (31.82 +/- 8.91 vs. 29.00 +/- 8.34,
      p = 0.039). CONCLUSIONS: OSA severity was independently associated with liver
      steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were
      associated with a statistically significant improvement on liver injury in OSA
      patients.

PMID- 29224043
TI  - Identification of human papillomavirus (HPV) subtype in oral cancer patients
      through microarray technology.
AB  - PURPOSE: Human papilloma virus (HPV) is the main source of cervical cancer. Many
      recent studies have revealed the prevalence and prognosis of HPV associated with
      oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in
      oral squamous cell carcinoma (OSCC). The purpose of this study was to determine
      the prevalence and prognosis of HPV associated with OSCC according to HPV and
      tumor types. MATERIALS AND METHODS: We used a DNA chip kit (MY-HPV chip kit (r),
      Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45,
      51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187
      patients. The prevalence was determined by Chi-square and Fisher's exact tests,
      and the prognosis was calculated by the Kaplan-Meier method and the log-rank
      test. RESULTS: The overall prevalence of HPV in OSCC was 7.0% for all HPV
      positives and 4.3% for high-risk HPV positives. The prevalence of HPV was
      significantly higher in individuals under 65 years old and in those with tumors
      in the tongue and gum regions. The prognosis did not differ between the HPV
      positive and -negative groups. Although the prevalence of HPV-positive cases in
      OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV
      associated OSCC should be considered in the evaluation and treatment of oral
      cancer patients. In addition, separating high- and low-risk groups based on the
      HPV status of other body parts might not be appropriate. DISCUSSION: The DNA
      microarray method can accurately detect known HPV subtypes simultaneously, but
      has limitations in detecting new subtypes. Vaccines can also be used to prevent
      HPV-associated OSCC in patients, so further studies on the prognosis and efficacy
      of vaccines should be undertaken.

PMID- 29224044
TI  - Pattern of care and impact of prognostic factors on the outcome of head and neck
      extramedullary plasmacytoma: a systematic review and individual patient data
      analysis of 315 cases.
AB  - INTRODUCTION: Head and neck extramedullary plasmacytoma is a rare localized
      plasma cell neoplasm. We intended to perform this review of the published
      literature to assess the demographic profile, pattern of care and survival
      outcomes. METHODS: Two authors independently searched PubMed, Google search and
      Cochrane library for eligible studies from 1950 till July 1, 2016, published in
      English language. RESULTS: Median age of the cohort was 57 years (range 11-85).
      Site-wise distributions were paranasal sinuses 22.3% (70), nasal cavity 17.5%
      (55), nasopharynx 10.8% (34). Median size of SEMP was 3 cm (range 0.3-12 cm).
      Treatment distribution was radiotherapy (RT) in 52% (164), surgery (S) 19% (60),
      chemotherapy (C) 5% (16), S + RT 23.49% (74),CRT 1.9% (6), S + C 0.6% (2), S + RT
      + C 0.95% (3).Radiation was used as a modality in 78.4%(247), surgery in
      44.1%(139), chemotherapy in 4.8%(15). Median radiation dose used was 45 Gy with
      range 20-61 Gy. Median overall survival (OS) was 40 months (range 0.5-298).
      Median local progression-free survival was 36 months (range 0-298). Median
      myeloma relapse-free survival was 36 months (range 0.5-298). Five- and 10-year OS
      was 78.33 and 68.61%. Five-year cause-specific survival (CSS) and 10-year CSS was
      90.15 and 83.31%. Five-year LPFS was 94.78%, and 10-year LPFS was 88.43%. Five
      year myeloma progression-free survival was 84.46%, and 10-year myeloma PFS was
      80.44%. The factors associated with risk of local relapse were site of disease
      (sinonasal), secretory EMP, type of treatment received (surgery + RT > RT alone >
      surgery on univariate analysis). Risk factors for myeloma relapse were coexisting
      diseases, site of disease (sinonasal), bony erosion, size of lesion > 5 cm and
      type of treatment received on univariate analysis. CONCLUSION: Our study shows
      that combined modality S + RT is superior compared to uni-modality in preventing
      local recurrence. Radiation dose of 45 Gy is optimal. Nodal irradiation has no
      impact on local recurrence.

PMID- 29224045
TI  - Association of Adolescent- and Caregiver-Reported Antiretroviral Therapy
      Adherence with HIV Viral Load Among Perinatally-infected South African
      Adolescents.
AB  - Accurate measurement of antiretroviral therapy (ART) adherence remains
      challenging and there are few data assessing the validity of self-reported
      adherence among perinatally HIV-infected adolescents. We examined adolescent and
      caregiver reports of adolescent adherence among perinatally-infected adolescents
      aged 9-14 years in Cape Town, South Africa, and explored factors that may modify
      associations between reported adherence and elevated viral load (VL). Among 474
      adolescents (median age 12.0 years; median duration of ART use 7.5 years),
      elevated VL and caregiver- and adolescent-report of missed ART doses were common.
      Elevated VL was particularly prevalent among older, male adolescents. Low
      moderate concordance was observed between caregiver and adolescent report. Among
      adolescents aged >= 12 years, caregiver- and adolescent-reported adherence was
      associated with elevated VL across most items assessed, but few significant
      associations were observed among adolescents < 12 years of age. Refined adherence
      measures and tools to identify adolescents who require adherence interventions
      are needed in this context.

PMID- 29224046
TI  - Impacts and Policy Implications of Metals Effluent Discharge into Rivers within
      Industrial Zones: A Sub-Saharan Perspective from Ethiopia.
AB  - Kombolcha, a city in Ethiopia, exemplifies the challenges and problems of the sub
      Saharan countries where industrialization is growing fast but monitoring
      resources are poor and information on pollution unknown. This study monitored
      metals Cr, Cu, Zn, and Pb concentrations in five factories' effluents, and in the
      effluent mixing zones of two rivers receiving discharges during the rainy seasons
      of 2013 and 2014. The results indicate that median concentrations of Cr in the
      tannery effluents and Zn in the steel processing effluents were as high as 26,600
      and 155,750 ug/L, respectively, much exceeding both the USEPA and Ethiopian
      emission guidelines. Cu concentrations were low in all effluents. Pb
      concentrations were high in the tannery effluent, but did not exceed emission
      guidelines. As expected, no metal emission guidelines were exceeded for the
      brewery, textile and meat processing effluents. Median Cr and Zn concentrations
      in the Leyole river in the effluent mixing zones downstream of the tannery and
      steel processing plant increased by factors of 52 (2660 compared with 51 ug Cr/L)
      and 5 (520 compared with 110 ug Zn/L), respectively, compared with stations
      further upstream. This poses substantial ecological risks downstream. Comparison
      with emission guidelines indicates poor environmental management by industries
      and regulating institutions. Despite appropriate legislation, no clear measures
      have yet been taken to control industrial discharges, with apparent mismatch
      between environmental enforcement and investment policies. Effluent management,
      treatment technologies and operational capacity of environmental institutions
      were identified as key improvement areas to adopt progressive sustainable
      development.

PMID- 29224047
TI  - Magnetic resonance imaging of cardiovascular thrombi in children.
AB  - Cardiovascular thrombosis is rare in children and usually occurs in the presence
      of predisposing conditions, such as indwelling vascular catheters, tumors,
      aneurysms, ventricular dysfunction, or after surgery. Clots can occur in the
      cardiac chambers, arteries or veins, or inside conduits. Detection of thrombi is
      feasible with a variety of magnetic resonance imaging (MRI) techniques, including
      unenhanced methods but also contrast-enhanced MR angiography. In this essay we
      illustrate the MRI appearance of cardiovascular thrombosis in children and
      suggest an imaging protocol based on our clinical experience.

PMID- 29224048
TI  - Comparison between whole-body and head and neck neurovascular coils for 3-T
      magnetic resonance proton resonance frequency shift thermography guidance in the
      head and neck region.
AB  - The purpose of this study is to compare the image quality of magnetic resonance
      (MR) treatment planning images and proton resonance frequency (PRF) shift
      thermography images and inform coil selection for MR-guided laser ablation of
      tumors in the head and neck region. Laser ablation was performed on an agar
      phantom and monitored via MR PRF shift thermography on a 3-T scanner, following
      acquisition of T1-weighted (T1W) planning images. PRF shift thermography images
      and T2-weighted (T2W) planning images were also performed in the neck region of
      five normal human volunteers. Signal-to-noise ratios (SNR) and temperature
      uncertainty were calculated and compared between scans acquired with the
      quadrature mode body integrated coil and a head and neck neurovascular coil. T1W
      planning images of the agar phantom produced SNRs of 4.0 and 12.2 for the
      quadrature mode body integrated coil and head and neck neurovascular coil,
      respectively. The SNR of the phantom MR thermography magnitude images obtained
      using the quadrature mode body integrated coil was 14.4 versus 59.6 using the
      head and neck coil. The average temperature uncertainty for MR thermography
      performed on the phantom with the quadrature mode body integrated coil was 1.1
      versus 0.3  degrees C with the head and neck coil. T2W planning images of the
      neck in five human volunteers produced SNRs of 28.3 and 91.0 for the quadrature
      mode body integrated coil and head and neck coil, respectively. MR thermography
      magnitude images of the neck in the volunteers obtained using the quadrature mode
      body integrated coil had a signal-to-noise ratio of 8.3, while the SNR using the
      head and neck coil was 16.1. The average temperature uncertainty for MR
      thermography performed on the volunteers with the body coil was 2.5 versus 1.6 
      degrees C with the head and neck neurovascular coil. The quadrature mode body
      integrated coil provides inferior image quality for both basic treatment planning
      sequences and MR PRF shift thermography compared with a neurovascular coil, but
      may nevertheless be adequate for clinical purposes.

PMID- 29224049
TI  - Enchondromatosis-associated oligodendroglioma: case report and literature review.
AB  - Enchondromatosis is a rare skeletal disorder characterized by the development of
      multiple enchondromas, which can also manifest non-cartilage tumors including
      gliomas. Here, we describe a genetic analysis of a low-grade glioma that
      developed in an enchondromatosis case. A 32-year-old man with a long history of
      enchondromatosis developed a left frontal tumor. The histopathological findings
      of his surgical specimen revealed characteristics of a low-grade glioma with an
      IDH1 c.395G>A (R132H) mutation and 1p/19q codeletion, which led to a definitive
      diagnosis of oligodendroglioma. A common point mutation in IDH1 (R132H) was
      detected in the patient's enchondroma and glioma-matched pair specimens. To the
      best of our knowledge, this is the first case of molecularly confirmed
      oligodendroglioma associated with enchondromatosis. Furthermore, identification
      of a common IDH1 mutation in enchondroma and oligodendroglioma-matched pair
      specimens supports the hypothesis that IDH1/2 mosaicism initiates tumorigenesis.

PMID- 29224050
TI  - MALDI Imaging Combined with Laser Microdissection-Based Microproteomics for
      Protein Identification: Application to Intratumor Heterogeneity Studies.
AB  - Matrix-assisted laser desorption ionization (MALDI) imaging is widely used for in
      situ proteomic mapping and finds multiple applications in pathology. However, low
      fragmentation yields in MALDI avoid an optimal identification of peptides from
      tissues. On the other hand, LMD-based microproteomic analyses allow for the
      identification of hundreds to thousands of proteins from small tissue regions.
      Herein, we present the combination of MALDI imaging and LMD-based microproteomic
      approaches for parallel identification. We illustrate the workflow with an
      application to intratumor heterogeneity studies.

PMID- 29224051
TI  - Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and
      Apoptotic Stress and Extends Chronological Lifespan.
AB  - The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase
      proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes
      cathepsin D. Mutation of CTSD gene in human resulted in a number of
      neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant
      cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen
      peroxide and acetic acid, respectively. pep4? cells also showed accumulation of
      reactive oxygen species (ROS), apoptotic markers, and reduced chronological
      lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from
      oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing
      apoptotic markers. The percentage viability of quercetin-treated pep4? cells was
      more pronounced and increased stress resistance against oxidant, apoptotic, and
      heat stress during chronological aging. From our experimental results, we
      concluded that quercetin protects yeast pep4 mutant cells from oxidative stress
      and apoptosis, thereby increasing viability during chronological aging.

PMID- 29224052
TI  - Arterial input function in a dedicated slice for cerebral perfusion measurements
      in humans.
AB  - OBJECT: We aimed to modify our previously published method for arterial input
      function measurements for evaluation of cerebral perfusion (dynamic
      susceptibility contrast MRI) such that it can be applied in humans in a clinical
      setting. MATERIALS AND METHODS: Similarly to our previous work, a conventional
      measurement sequence for dynamic susceptibility contrast MRI is extended with an
      additional measurement slice at the neck. Measurement parameters at this slice
      were optimized for the blood signal (short echo time, background suppression,
      magnitude and phase images). Phase-based evaluation of the signal in the carotid
      arteries is used to obtain quantitative arterial input functions. RESULTS: In all
      pilot measurements, quantitative arterial input functions were obtained. The
      resulting absolute perfusion parameters agree well with literature values (gray
      and white matter mean values of 46 and 24 mL/100 g/min, respectively, for
      cerebral blood flow and 3.0% and 1.6%, respectively, for cerebral blood volume).
      CONCLUSIONS: The proposed method has the potential to quantify arterial input
      functions in the carotid arteries from a direct measurement without any
      additional normalization.

PMID- 29224053
TI  - Spontaneous bacteremia and spontaneous bacterial peritonitis share similar
      prognosis in patients with cirrhosis: a cohort study.
AB  - BACKGROUND AND AIMS: Spontaneous bacteremia is a poorly characterized infection
      in patients with cirrhosis. We compared the incidence of mortality and acute
      kidney injury in patients with spontaneous bacterial peritonitis and spontaneous
      bacteremia, and identified risk factors for mortality and acute kidney injury in
      patients with spontaneous bacteremia. METHODS: We performed a retrospective
      cohort study of patients with cirrhosis and spontaneous bacteremia or spontaneous
      bacterial peritonitis from 2008 to 2016 at Hospital Italiano, Buenos Aires. We
      compared the cumulative incidence of acute kidney injury and death between the
      two infections, and identified risk factors for these outcomes in patients with
      spontaneous bacteremia. RESULTS: Seventy-one patients with spontaneous bacteremia
      and 55 patients with spontaneous bacterial peritonitis were included. Most
      infections were nosocomial. Overall, 26% of bacteria were resistant and 11% multi
      resistant. We found no significant association between acute kidney injury
      [subhazard ratio (sHR) 1.05 (95% confidence interval, CI 0.67-1.63, p = 0.83)] or
      death [sHR 1.15 (95% CI 0.60-2.20, p = 0.68)] and type of spontaneous infection
      in multivariate analyses adjusting for basal Model for End-Stage Liver Disease
      (MELD) score. In patients with spontaneous bacteremia, baseline MELD score was
      independently associated with acute kidney injury [sHR 1.07 (95% CI 1.03-1.11, p
      = 0.001)] and death [sHR 1.07 (95% CI 1.02-1.15, p = 0.03)]. CONCLUSIONS: Short
      term acute kidney injury and mortality rates were similar in patients with
      spontaneous bacteremia and spontaneous bacterial peritonitis. Risk assessment of
      patients with spontaneous bacteremia can be performed with baseline MELD score.

PMID- 29224054
TI  - Lesion characteristics and procedural outcomes of re-attempted percutaneous
      coronary interventions for chronic total occlusion.
AB  - This study was performed to investigate lesion characteristics and procedural
      outcomes of re-attempted percutaneous coronary intervention (PCI) for chronic
      total occlusion (CTO). Prior failure of percutaneous revascularization of CTO has
      been identified as an independent predictor of failure at subsequent attempts.
      However, procedural outcomes of re-attempted PCI for CTO have not been
      elucidated. We evaluated lesion characteristics and procedural outcomes in 310
      consecutive patients undergoing CTO-PCI, and compared the results between re
      attempted (n = 59) and initial procedures (n = 251). Overall, 266 CTO lesions
      (85.8%) were treated successfully. In addition, the technical success rate in the
      re-attempted CTO lesions was 69.5% (41 of 59), although this was lower than for
      initially attempted lesions (89.6%, 225 of 251; P = 0.0021). In the details of
      reasons of previous failures, treatment devices failed to cross even after
      guidewire cross and procedure discontinuation due to management of complications
      achieved higher rates of technical success compared to those with the inability
      of guidewire crossing in re-attempted CTO-PCI (87.5 and 85.7 vs. 65.9%,
      respectively). CTO lesions in which PCI was re-attempted had more complex
      features, including calcification, tortuous morphology, and long lesion length,
      whereas patient demographics were similar. Re-attempted CTO lesions required
      complex procedures, including the retrograde approach (55.9 vs. 13.9%, P <
      0.001), longer fluoroscopic time, and larger radiation dose. Meanwhile, rates of
      complications and in-hospital MACCE were similarly low in both groups. The
      technical success rates of re-attempted CTO-PCI lesions were acceptable.
      Furthermore, CTO-PCIs in re-attempted lesions were as safe as initially attempted
      CTO-PCI. However, re-attempted CTO-PCI lesions showed features of high anatomical
      complexity that required more complex and longer procedures, including the
      retrograde approach, for successful interventional revascularization. Re
      attempted CTO-PCI due to treatment devices failed to cross even after guidewire
      cross and procedure discontinuation due to management of complications in
      previous attempt had higher success rates that those with the inability of
      guidewire crossing.

PMID- 29224055
TI  - Peri-operative antibiotic treatment of bacteriuria reduces early deep surgical
      site infections in geriatric patients with proximal femur fracture.
AB  - PURPOSE: The aim of this study was to conduct a re-evaluation of current
      strategies for peri-operative prophylaxis of infections in orthopaedic surgery of
      geriatric patients (>=65 years) with proximal femoral fractures (PFF). METHODS:
      Between 01/2010 and 08/2014 all post-operative infections after stabilization of
      PFF of 1,089 geriatric patients were recorded retrospectively. All patients pre
      operatively received a single dose of 1.5 g cefuroxime (group 1). These were
      compared to prospectively determined post-operative rates of surgical site
      infection (SSI) of 441 geriatric patients, which were operated on between 09/2014
      and 03/2017 due to PFF. In this second group we investigated the urinary tract on
      admission. Bacteriuria was treated with the pre-operative single dose of 1.5 g
      cefuroxime along with ciprofloxacin for five days, beginning on admission. Level
      of significance was set to p < 0.05. RESULTS: A total of 141 patients of group 2
      had a bacteriuria. Seventy-seven of these patients revealed biochemical signs of
      manifest urinary tract infection. Multi-resistant pathogens were found in 15
      patients and pathogens were cefuroxime-resistant in 37. The differences of SSI
      after at least three months were 2.1% in group 1 and 0.45% in group 2 for all
      patients with surgery of PFF (p < 0.02) and for those with arthroplasty (p <
      0.037) significant. CONCLUSIONS: The immediate antibiotic therapy of a prevalent
      bacteriuria for five days decreases the risk of SSI after surgery of PFF. Our
      single-centre study can only point out the problem of prevalent reservoirs of
      pathogens and the need for treatment. Evidence-based therapy concepts
      (indications of antibiotics, classes, duration) have to be developed in multi
      centric and prospective studies.

PMID- 29224056
TI  - A 5-year multicenter prospective cohort study on the long-term visual prognosis
      and predictive factors for visual outcome in Japanese patients with age-related
      macular degeneration: the AMD2000 study.
AB  - PURPOSE: In this study (AMD2000), we aimed to determine the visual prognosis of
      Japanese patients with age-related macular degeneration (AMD). METHODS: This was
      a multicenter prospective observational cohort study. In total, 460 patients with
      AMD were recruited from April 2006 to March 2009 from 18 clinical trial sites in
      Japan. They were followed up for 5 years, as they continued to receive medical
      treatment. RESULTS: Of the 409 study eyes followed up for at least 1 year, 243
      eyes (59.4%) were treated with photodynamic therapy (PDT) using verteporfin, and
      58 eyes (14.2%) were treated with intravitreal injections of antivascular
      endothelial growth factor agents as the initial treatment. The mean best
      corrected visual acuities (BCVA) for typical AMD (tAMD; 0.688 +/- 0.498) and
      polypoidal choroidal vasculopathy (PCV; 0.451 +/- 0.395) were significantly less
      at 2 years (tAMD, 0.779 +/- 0.632, P < 0.05; PCV, 0.534 +/- 0.618, P < 0.05) and
      at 5 years (AMD, 0.873 +/- 0.718, P < 0.05; PCV, 0.635 +/- 0.668, P < 0.05) than
      at baseline. In eyes with tAMD, absence of blocked fluorescence was associated
      with 5-year maintenance of the baseline BCVA. Regarding PCV, the presence of
      polypoidal lesions and cystoid macular edema as well as the lesion size was
      associated with 5-year maintenance of the baseline BCVA. In some patients, the
      diagnosis changed: of the 192 eyes initially diagnosed with typical AMD, 19 were
      newly diagnosed with PCV during follow-up. CONCLUSION: Maintaining the baseline
      BCVA over the long term is difficult in Japanese eyes with wet AMD.

PMID- 29224057
TI  - Identifying factors associated with need for flexible ureteroscope repair: a
      Western Endourology STone (WEST) research consortium prospective cohort study.
AB  - Maintenance of flexible ureteroscopes can involve high costs and administrative
      burden. Instrument fragility necessitates eventual repair, rendering scopes
      inaccessible during refurbishment. We conducted a multi-institutional prospective
      cohort study to identify perioperative factors influencing flexible ureteroscope
      durability. Patients undergoing flexible ureteroscopy (URS) at six United States
      endourology centers were enrolled between August 2014 and June 2015. Surgeon self
      reported concern and satisfaction with scope performance as well as upward and
      downward angles of deflection for each scope tip were measured before and after
      each procedure. The need for scope repair was determined by the operating surgeon
      at the time of the procedure and recorded. 424 URS cases using 74 flexible
      ureteroscopes were identified. Scope repair was required in 28 cases (6.6%)
      involving 26 scopes (35.1%). Upon univariate analysis, shorter patient height,
      absence of guidewire use, presence of a ureteral access sheath (UAS), longer
      procedure time, larger stone size, lithotrite type, surgeon training level, and
      self-reported concern were associated with scope repair. Upon multivariate
      analysis, UAS use (OR = 2.53, p = 0.005) and degree loss of scope upward flexion
      during a case (OR = 1.02, p = 0.03) increased the odds of a scope needing repair
      while the use of safety guidewire decreased the odds of a scope repair (OR =
      0.50, p = 0.045). Lithotrite use and surgeon concern were associated with degree
      loss of scope upward flexion. The use of a UAS, absence of a safety guidewire,
      and the loss of upward ureteroscope flexion should be considered when evaluating
      means of optimizing reusable ureteroscope durability.

PMID- 29224058
TI  - Systematic assessment and characterization of chronic pain in multiple sclerosis
      patients.
AB  - Pain is one of the most disabling clinical symptoms in patients with multiple
      sclerosis (MS). Several studies have already assessed the prevalence of pain in
      MS patients, reporting variable results, probably due to methodological
      differences. The aim of this single-centre cross-sectional study was to define
      the prevalence and characteristics of chronic pain in a population of MS patients
      using validated tools, and to analyse these data in relation to demographic and
      clinical features, including disease duration and disability (EDSS and its single
      functional system scores). Of 397 enrolled patients, 23 were excluded due to a
      Beck's Depression Inventory Score > 19. In the remaining 374 patients, the
      overall prevalence of chronic pain was 52.1%, most frequently affecting the lower
      limbs (36.9%). Neuropathic pain was the most frequent type of chronic pain (89
      patients, overall prevalence of 23.7%) and was associated with a sensory
      functional system involvement. Pain intensity was significantly higher in
      patients with neuropathic pain as opposed to patients with non-neuropathic pain.
      Patients with chronic pain and, in particular, patients with neuropathic pain had
      significantly higher EDSS scores than those without pain. Only 24% of patients
      with chronic pain and 33% of patients with neuropathic pain were on a specific
      long-lasting treatment for pain. The present study supports the routine
      assessment of neuropathic pain in MS patients, especially in those with a sensory
      functional system involvement, in order to avoid underdiagnosing and
      undertreating a potentially disabling condition.

PMID- 29224059
TI  - Lower complication rate and faster return to sports in patients with acute
      syndesmotic rupture treated with a new knotless suture button device.
AB  - PURPOSE: Suture button devices for tibiofibular syndesmosis injuries provide
      semirigid dynamic stabilization, but complications including knot irritation have
      been reported. No randomized trials of the new knotless suture button devices
      have been performed. We hypothesized that knotless suture button devices
      eliminate knot irritation and facilitate quicker return to sports. This study was
      performed to compare the clinical outcomes, complication rates, and time to
      return to sports between a new knotless suture button device and syndesmotic
      screw fixation. METHODS: This study included 54 patients treated for ankle
      syndesmotic injury from 2012 to 2014 with a knotless suture button device or
      syndesmotic screw fixation. Clinical outcomes were measured using the American
      Orthopaedics Foot and Ankle Society score, Foot and Ankle Disability Index,
      Olerud and Molander score, and visual analog scale for pain and function.
      Secondary outcome measures were the complication rate and time required to return
      to sports. Patients underwent clinical and radiological evaluations
      preoperatively and three times during the 1-year postoperative follow-up.
      RESULTS: 54 of 62 eligible patients were analyzed, median age 37 (18-60) and
      underwent the 1-year follow-up. The screw fixation and knotless suture button
      groups comprised 26 and 28 patients, respectively. The complication rate was
      significantly lower (p = 0.03) and time to return to sports was significantly
      shorter in the knotless suture button than screw fixation group (average, 14
      versus 19 weeks, respectively; p = 0.006). No significant differences were
      identified in clinical outcomes or visual analog scale scores for pain and
      function between the groups. Age, injury mechanism, and body mass index did not
      significantly affect the time required to return to sports activities. The type
      of fixation was the only independent variable that reached statistical
      significance (p = 0.006). CONCLUSION: Syndesmotic screw fixation and the new
      knotless suture button device both resulted in good clinical results. Lower
      complication rate and the earlier time to return to sports make the new knotless
      suture button device recommendable especially for highly active patients. LEVEL
      OF EVIDENCE: Randomized controlled trial, Level I.

PMID- 29224060
TI  - Differences between osteoradionecrosis and medication-related osteonecrosis of
      the jaw.
AB  - PURPOSE: The appearance of osteoradionecrosis (ORN) and medication-related
      osteonecrosis of the jaw (MRONJ) is similar, but clinically important differences
      between ORN and MRONJ exist. The aim of this study was to compare the clinical
      data between ORN and MRONJ and to reveal the critical differences between these
      diseases. METHODS: We retrospectively reviewed the epidemiological data, clinical
      findings, and treatment in 27 ORN and 61 MRONJ patients. Radiographic signs
      before the initiation of treatment were also assessed. RESULTS: The median age (P
      = 0.0474) and the ratio of female to male patients (P < 0.0001) were
      significantly higher in MRONJ patients. There were significantly more MRONJ
      patients who reported a history of pain when compared with ORN patients (P =
      0.0263). As an aetiological factor, tooth extraction was significantly more
      relevant to MRONJ than ORN (P = 0.0352). When assessing the radiographic signs on
      computed tomographic images, periosteal reaction was found only in MRONJ patients
      (P = 0.0158). Minimal debridement was performed significantly more frequently for
      MRONJ (P = 0.0093), and by contrast, surgical resection was performed more
      frequently for ORN (P = 0.0002). CONCLUSIONS: Understanding the clinical and
      underlying pathological differences between ORN and MRONJ probably contributes to
      the selection of appropriate treatment for each patient.

PMID- 29224061
TI  - Cyclic fatigue and torsional strength of three different thermally treated
      reciprocating nickel-titanium instruments.
AB  - OBJECTIVES: The aim of this study was to evaluate the cyclic and torsional
      fatigue resistance of the reciprocating single-file systems Reciproc Blue 25.08
      (VDW GmbH, Munich, Germany), Prodesign R 25.06 (Easy Dental Equipment, Belo
      Horizonte, Brazil), and WaveOne Gold 25.07 (Dentsply/Tulsa Dental Specialties,
      Tulsa, OK, USA). MATERIALS AND METHODS: Sixty reciprocating instruments of the
      systems Reciproc Blue R25 (RB #25 .08 taper), Prodesign R (PDR #25 .06 taper),
      and WaveOne Gold (WOG #25 .07 taper) (n = 20) were used. Cyclic fatigue
      resistance testing was performed by measuring the time to failure in an
      artificial stainless steel canal with a 60 degrees  angle of curvature and a 5-mm
      radius located 5 mm from the tip (n = 10). The torsional test (ISO 3630-1)
      evaluated the torque and angle of rotation at failure of new instruments (n = 10)
      in the portion 3 mm from the tip. The fractured surface of each fragment was also
      observed using scanning electron microscopy (SEM). In addition, a supplementary
      examination was performed to measure the cross-sectional area of each instrument
      3 and 5 mm from the tip. The data were analyzed using one-way ANOVA and Tukey's
      test, and the level of significance was set at 5%. RESULTS: The cyclic fatigue
      resistance values of PDR 25.06 were significantly higher (P < 0.05). RB 25.08
      showed higher fatigue resistance than WOG 25.07 (P < 0.05). The torsional test
      showed that PDR 25.06 had lower torsional strength (P < 0.05). No differences
      were observed between RB 25.08 and WOG 25.07 (P > 0.05). PDR 25.06 showed higher
      angular rotation values than RB 25.08 and WOG 25.07 (P < 0.05). RB 25.08
      presented higher angular rotation than WOG 25.07 (P < 0.05). The cross-sectional
      area analysis showed that PDR 25.06 presented the smallest cross-sectional areas
      at 3 and 5 mm from the tip (P < 0.05). CONCLUSION: PDR 25.06 presented the
      highest cyclic fatigue resistance and angular rotation until fracture compared to
      RB 25.08 and WOG 25.07. In addition, RB 25.08 and WOG 25.07 had higher torsional
      strength than PDR 25.06. CLINICAL RELEVANCE: In endodontic practice, thermally
      treated reciprocating instruments have been used for the root canal preparation
      of curved and constricted canals; therefore, these instruments should present
      high flexibility and suitable torsional strength to minimize the risk of
      instrument fracture.

PMID- 29224062
TI  - Relationship between caries experience and demarcated hypomineralised lesions
      (including MIH) in the permanent dentition of 15-year-olds.
AB  - OBJECTIVE: This cross-sectional study compared the caries experience in 15-year
      olds with and without demarcated hypomineralised lesions (DHL) in permanent
      teeth. MATERIAL AND METHODS: One thousand three hundred and two 15-year-old
      adolescents from two ongoing birth cohorts (GINIplus15 and LISAplus15) were
      examined to determine non-cavitated carious lesions (NCCL) and the DMF index.
      Furthermore, DHL was scored on all permanent teeth/surfaces according to the
      molar-incisor hypomineralisation criteria of the European Academy of Paediatric
      Dentistry (MIH/EAPD). Adolescents with DHL were categorised into those with a
      minimum of one DHL in the permanent dentition (DHL >= 1), with DHL on at least
      one first permanent molar (MIH/EAPD) and with DHL on at least one first permanent
      molar and permanent incisor (MIH/Severe). The study was conducted in the
      metropolitan area of Munich. RESULTS: The proportion of children without caries
      amounted to 63.7% (DMF > 0) and 26.0% (D1-4MF > 0); the caries experience was
      mean = 4.0(SD = 5.2) NCCL/T and 0.9(1.7) DMF/T. Existence of DHL >= 1, MIH/EAPD
      and MIH/Severe was detected in 40.2, 17.2 and 9.8% of all adolescents,
      respectively. The corresponding DMF/T values were: no DHL 0.9(1.7); DHL >= 1
      1.0(1.7); MIH/EAPD 1.1(1.6); MIH/Severe 1.1(1.7). The group of adolescents with
      MIH/EAPD and MIH/Severe were found to have statistically higher caries rates in
      comparison to those with no DHL. CONCLUSIONS: Caries and DHL are prevalent and
      influenced the dental health of 15-year-old adolescents. A significant positive
      association existed between the presence of caries and DHL. CLINICAL RELEVANCE:
      Children with MIH/EAPD or MIH/Severe had a higher probability to develop carious
      lesions in the permanent dentition.

PMID- 29224063
TI  - An efficient scheme for mental task classification utilizing reflection
      coefficients obtained from autocorrelation function of EEG signal.
AB  - Classification of different mental tasks using electroencephalogram (EEG) signal
      plays an imperative part in various brain-computer interface (BCI) applications.
      In the design of BCI systems, features extracted from lower frequency bands of
      scalp-recorded EEG signals are generally considered to classify mental tasks and
      higher frequency bands are mostly ignored as noise. However, in this paper, it is
      demonstrated that high frequency components of EEG signal can provide
      accommodating data for enhancing the classification performance of the mental
      task-based BCI. Instead of using autoregressive (AR) parameters considering AR
      modeling of EEG data, reflection coefficients obtained from EEG signal are
      proposed as potential features. From a given frame of EEG data, reflection
      coefficients are directly extracted by using the autocorrelation values in a
      recursive fashion, which avoids matrix inversion and computation of AR
      parameters. Use of reflection coefficients not only provides an effective feature
      vector for EEG signal classification but also offers very low computational
      burden. Support vector machine classifier is deployed in leave-one-out cross
      validation manner to carry out classification process. Extensive simulation is
      done on an openly accessible dataset containing five different mental tasks. It
      is found that the proposed scheme can classify mental tasks with a very high
      level of accuracy as well as low time complexity in contrast with some of the
      existing strategies.

PMID- 29224064
TI  - An Integrated Polysome Profiling and Ribosome Profiling Method to Investigate In
      Vivo Translatome.
AB  - Recent advances in global translatome analysis technologies enable us to
      understand how translational regulation of gene expression modulates cellular
      functions. In this chapter, we present an integrated method to measure various
      aspects of translatome by polysome profiling and ribosome profiling using
      purified B cells. We standardized our protocols to directly compare the results
      from these two approaches. Parallel assessment of translatome with these two
      approaches can generate a comprehensive picture on how translational regulation
      determines protein output.

PMID- 29224065
TI  - Measuring Nascent Transcripts by Nascent-seq.
AB  - A complete understanding of transcription and co-transcriptional RNA processing
      events by polymerase requires precise and robust approaches to visualize
      polymerase progress and quantify nascent transcripts on a genome-wide scale.
      Here, we present a transcriptome-wide method to measure the level of nascent
      transcribing RNA in a fast and unbiased manner.

PMID- 29224066
TI  - Genome-Wide Copy Number Alteration Detection in Preimplantation Genetic
      Diagnosis.
AB  - Shallow whole genome sequencing has recently been introduced for genome-wide
      detection of chromosomal copy number alterations (CNAs) in preimplantation
      genetic diagnosis (PGD), using only 4-7 trophectoderm cells biopsied from day-5
      embryos. This chapter describes the complete method, starting from whole genome
      amplification (WGA) on isolated blastomere(s), up to data analysis for CNA
      detection. The process is described generically and can also be used to perform
      CNA analysis on a limited number of cells (down to a single cell) in other
      applications. This unique description also includes some tips and tricks to
      increase the chance of success.

PMID- 29224067
TI  - Multiplexed Targeted Sequencing for Oxford Nanopore MinION: A Detailed Library
      Preparation Procedure.
AB  - MinION is a small form factor sequencer recently retailed by Oxford Nanopore
      technologies. This lighter-sized USB3.0-interfaced device uses innovative
      nanotechnology to generate extra-long reads from libraries prepared using only
      standard molecular biology lab equipment. The flexibility and the portability of
      the platform makes it ideal for point-of-interest and real-time surveillance
      applications. However, MinION's limited capacity is not enough for the study of
      specific targets within larger genomes. Apart from just PCR-amplifying regions of
      interest, the capture of long reads spanning the edges of known-unknown genomic
      regions is of great importance for structural studies, such as the identification
      of mobile elements' integrations sites, bridging over low complexity repetitive
      regions etc.In this study, using MinION-kit-included and commercially available
      reagents, we have developed an easy and versatile wet-lab procedure for the
      targeted enrichment of MinION libraries, capturing DNA fragments of interest
      before the ligation of the sensitive MinION sequencing-adapters. This method
      allows for simultaneous target-enrichment and barcode-multiplexing of up to 12
      libraries, which can be loaded in the same sequencing run.

PMID- 29224068
TI  - Hi-Plex for Simple, Accurate, and Cost-Effective Amplicon-based Targeted DNA
      Sequencing.
AB  - Hi-Plex is a suite of methods to enable simple, accurate, and cost-effective
      highly multiplex PCR-based targeted sequencing (Nguyen-Dumont et al.,
      Biotechniques 58:33-36, 2015). At its core is the principle of using gene
      specific primers (GSPs) to "seed" (or target) the reaction and universal primers
      to "drive" the majority of the reaction. In this manner, effects on amplification
      efficiencies across the target amplicons can, to a large extent, be restricted to
      early seeding cycles. Product sizes are defined within a relatively narrow range
      to enable high-specificity size selection, replication uniformity across target
      sites (including in the context of fragmented input DNA such as that derived from
      fixed tumor specimens (Nguyen-Dumont et al., Biotechniques 55:69-74, 2013; Nguyen
      Dumont et al., Anal Biochem 470:48-51, 2015), and application of high-specificity
      genetic variant calling algorithms (Pope et al., Source Code Biol Med 9:3, 2014;
      Park et al., BMC Bioinformatics 17:165, 2016). Hi-Plex offers a streamlined
      workflow that is suitable for testing large numbers of specimens without the need
      for automation.

PMID- 29224069
TI  - ClickSeq: Replacing Fragmentation and Enzymatic Ligation with Click-Chemistry to
      Prevent Sequence Chimeras.
AB  - We recently reported a fragmentation-free method for the synthesis of Next
      Generation Sequencing libraries called "ClickSeq" that uses biorthogonal click
      chemistry in place of enzymes for the ligation of sequencing adaptors. We found
      that this approach dramatically reduces artifactual chimera formation, allowing
      the study of rare recombination events that include viral replication
      intermediates and defective-interfering viral RNAs. ClickSeq illustrates how
      robust, bio-orthogonal chemistry can be harnessed in vitro to capture and dissect
      complex biological processes. Here, we describe an updated protocol for the
      synthesis of "ClickSeq" libraries.

PMID- 29224070
TI  - Genome-Wide Analysis of DNA Methylation in Single Cells Using a Post-bisulfite
      Adapter Tagging Approach.
AB  - DNA methylation is an epigenetic mark implicated in the regulation of key
      biological processes. Using high-throughput sequencing technologies and bisulfite
      based approaches, it is possible to obtain comprehensive genome-wide maps of the
      mammalian DNA methylation landscape with a single-nucleotide resolution and
      absolute quantification. However, these methods were only applicable to bulk
      populations of cells. Here, we present a protocol to perform whole-genome
      bisulfite sequencing on single cells (scBS-Seq) using a post-bisulfite adapter
      tagging approach. In this method, bisulfite treatment is performed prior to
      library generation in order to both convert unmethylated cytosines and fragment
      DNA to an appropriate size. Then DNA fragments are pre-amplified with concomitant
      integration of the sequencing adapters, and libraries are subsequently amplified
      and indexed by PCR. Using scBS-Seq we can accurately measure DNA methylation at
      up to 50% of individual CpG sites and 70% of CpG islands.

PMID- 29224071
TI  - Sequencing of Genomes from Environmental Single Cells.
AB  - Sequencing of single bacterial and archaeal cells is an important methodology
      that provides access to the genetic makeup of uncultivated microorganisms. We
      here describe the high-throughput fluorescence-activated cell sorting-based
      isolation of single cells from the environment, their lysis and strand
      displacement-mediated whole genome amplification. We further outline 16S rRNA
      gene sequence-based screening of single-cell amplification products, their
      preparation for Illumina sequencing libraries, and finally propose computational
      methods for read and contig level quality control of the resulting sequence data.

PMID- 29224072
TI  - SNP Discovery from Single and Multiplex Genome Assemblies of Non-model Organisms.
AB  - Population genetic studies of non-model organisms often rely on initial
      ascertainment of genetic markers from a single individual or a small pool of
      individuals. This initial screening has been a significant barrier to beginning
      population studies on non-model organisms (Aitken et al., Mol Ecol 13:1423-1431,
      2004; Morin et al., Trends Ecol Evol 19:208-216, 2004). As genomic data become
      increasingly available for non-model species, SNP ascertainment from across the
      genome can be performed directly from published genome contigs and short-read
      archive data. Alternatively, low to medium genome coverage from shotgun NGS
      library sequencing of single or pooled samples, or from reduced-representation
      libraries (e.g., capture enrichment; see Ref. "Hancock-Hanser et al., Mol Ecol
      Resour 13:254-268, 2013") can produce sufficient new data for SNP discovery with
      limited investment. We describe protocols for assembly of short read data to
      reference or related species genome contig sequences, followed by SNP discovery
      and filtering to obtain an optimal set of SNPs for population genotyping using a
      variety of downstream high-throughput genotyping methods.

PMID- 29224073
TI  - CleanTag Adapters Improve Small RNA Next-Generation Sequencing Library
      Preparation by Reducing Adapter Dimers.
AB  - Next-generation small RNA sequencing is a valuable tool which is increasing our
      knowledge regarding small noncoding RNAs and their function in regulating genetic
      information. Library preparation protocols for small RNA have thus far been
      restricted due to higher RNA input requirements (>10 ng), long workflows, and
      tedious manual gel purifications. Small RNA library preparation methods focus
      largely on the prevention or depletion of a side product known as adapter dimer
      that tends to dominate the reaction. Adapter dimer is the ligation of two
      adapters to one another without an intervening library RNA insert or any useful
      sequencing information. The amplification of this side reaction is favored over
      the amplification of tagged library since it is shorter. The small size
      discrepancy between these two species makes separation and purification of the
      tagged library very difficult. Adapter dimer hinders the use of low input samples
      and the ability to automate the workflow so we introduce an improved library
      preparation protocol which uses chemically modified adapters (CleanTag) to
      significantly reduce the adapter dimer. CleanTag small RNA library preparation
      workflow decreases adapter dimer to allow for ultra-low input samples (down to
      approx. 10 pg total RNA), elimination of the gel purification step, and
      automation. We demonstrate how to carry out this streamlined protocol to improve
      NGS data quality and allow for the use of sample types with limited RNA material.

PMID- 29224074
TI  - Sampling, Extraction, and High-Throughput Sequencing Methods for Environmental
      Microbial and Viral Communities.
AB  - The emergence of high-throughput sequencing technologies has deepened our
      understanding of complex microbial communities and greatly facilitated the study
      of as-yet uncultured microbes and viruses. Studies of complex microbial
      communities require high-quality data to generate valid results. Here, we detail
      current methods of microbial and viral community sample acquisition, DNA
      extraction, sample preparation, and sequencing on Illumina high-throughput
      platforms. While using appropriate analytical tools is important, it must not
      overshadow the need for establishing a proper experimental design and obtaining
      sufficient numbers of samples for statistical purposes. Researchers must also
      take care to sample biologically relevant sites and control for potential
      confounding factors (e.g., contamination).

PMID- 29224075
TI  - A Bloody Primer: Analysis of RNA-Seq from Tissue Admixtures.
AB  - RNA sequencing is a powerful technology that allows for unbiased profiling of the
      entire transcriptome. The analysis of transcriptome profiles from heterogeneous
      tissues, cell admixtures with relative proportions that can vary several fold
      across samples, poses a significant challenge. Blood is perhaps the most
      egregious example. Here, we describe in detail a computational pipeline for RNA
      Seq data preparation and statistical analysis, with development of a means of
      estimating the cell type composition of blood samples from their bulk RNA-Seq
      profiles. We also illustrate the importance of adjusting for the potential
      confounding effect of cellular heterogeneity in the context of statistical
      inference in a whole blood RNA-Seq dataset.

PMID- 29224076
TI  - Next-Generation Sequencing of Genome-Wide CRISPR Screens.
AB  - Genome-wide functional genomic screens utilizing the clustered regularly
      interspaced short palindromic repeats (CRISPR)-Cas9 system have proven to be a
      powerful tool for systematic genomic perturbation in mammalian cells and provide
      an alternative to previous screens utilizing RNA interference technology. The
      wide availability of these libraries through public plasmid repositories as well
      as the decreasing cost and speed in quantifying these screens using high
      throughput next-generation sequencing (NGS) allows for the adoption of the
      technology in a variety of laboratories interested in diverse biologic questions.
      Here, we describe the protocol to generate next-generation sequencing libraries
      from genome-wide CRISPR genomic screens.

PMID- 29224077
TI  - Gene Profiling and T Cell Receptor Sequencing from Antigen-Specific CD4 T Cells.
AB  - The paucity of pathogenic T cells in circulating blood limits the information
      delivered by bulk analysis. Toward diagnosis and monitoring of treatments of
      autoimmune diseases, we have devised single-cell analysis approaches capable of
      identifying and characterizing rare circulating CD4 T cells.

PMID- 29224078
TI  - Investigate Global Chromosomal Interaction by Hi-C in Human Naive CD4 T Cells.
AB  - Hi-C is a methodology developed to reveal chromosomal interactions from a genome
      wide perspective. Here, we described a protocol for generating Hi-C sequencing
      libraries in resting and activated human naive CD4 T cells to investigate
      activation-induced chromatin structure re-arrangement in T cell activation
      followed by a section reviewing the general concepts of Hi-C data analysis.

PMID- 29224079
TI  - Primer Extension, Capture, and On-Bead cDNA Ligation: An Efficient RNAseq Library
      Prep Method for Determining Reverse Transcription Termination Sites.
AB  - In this chapter, we describe a method for making Illumina-compatible sequencing
      libraries from RNA. This protocol can be used for standard RNAseq analysis for
      detecting differentially expressed genes. In addition, this protocol is ideally
      suited for adapting to RIPseq, 5'-RACE, RNA structural probing, nascent RNA
      sequencing, and other protocols where polymerase termination sites need to be
      profiled. The utilization of solid-phase bead chemistries facilitates simple
      workflow and efficient library yields.

PMID- 29224081
TI  - Electrochemical Applications in Metal Bioleaching.
AB  - Biohydrometallurgy comprises the recovery of metals by biologically catalyzed
      metal dissolution from solids in an aqueous solution. The application of this
      kind of bioprocessing is described as "biomining," referring to either
      bioleaching or biooxidation of sulfide metal ores. Acidophilic iron- and sulfur
      oxidizing microorganisms are the key to successful biomining. However, minerals
      such as primary copper sulfides are recalcitrant to dissolution, which is
      probably due to their semiconductivity or passivation effects, resulting in low
      reaction rates. Thus, further improvements of the bioleaching process are
      recommendable. Mineral sulfide dissolution is based on redox reactions and can be
      accomplished by electrochemical technologies. The impact of electrochemistry on
      biohydrometallurgy affects processing as well as analytics. Electroanalysis is
      still the most widely used electrochemical application in mineralogical research.
      Electrochemical processing can contribute to bioleaching in two ways. The first
      approach is the coupling of a mineral sulfide to a galvanic partner or
      electrocatalyst (spontaneous electron transfer). This approach requires only low
      energy consumption and takes place without technical installations by the
      addition of higher redox potential minerals (mostly pyrite), carbonic material,
      or electrocatalytic ions (mostly silver ions). Consequently, the processed
      mineral (often chalcopyrite) is preferentially dissolved. The second approach is
      the application of electrolytic bioreactors (controlled electron transfer). The
      electrochemical regulation of electrolyte properties by such reactors has found
      most consideration. It implies the regulation of ferrous and ferric ion ratios,
      which further results in optimized solution redox potential, less passivation
      effects, and promotion of microbial activity. However, many questions remain open
      and it is recommended that reactor and electrode designs are improved, with the
      aim of finding options for simplified biohydrometallurgical processing. This
      chapter focuses on metal sulfide dissolution via bioleaching and does not include
      other biohydrometallurgical processes such as microbial metal recovery from
      solution.

PMID- 29224080
TI  - Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult
      Population: a Nation-Wide, Health and Nutrition Survey.
AB  - Previous studies have shown that there is a controversial relationship between
      iron homeostasis and obesity. This study aims to explore the relationship of
      anemia and iron status with different body size phenotypes in adult Chinese
      population. Using information on iron status-related parameters and lifestyle
      data from 8462 participants of the 2009 wave of China Health and Nutrition Survey
      (2009 CHNS), we performed multivariable logistic regression analyses to estimate
      the odds ratios (ORs) for the risk of anemia and iron parameters according to
      different body size phenotypes. Participants with higher body mass index (BMI)
      had a lower anemia prevalence with significant trends in both metabolic status
      groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor
      (sTfR)/log ferritin index were significant in different metabolic status groups
      and in different body size phenotypes, respectively. The ORs for higher ferritin
      and transferrin increased across different body size phenotypes in both genders,
      and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association
      was still statistically significant after adjustment for multiple confounders. We
      found an inverse association of BMI levels with the prevalence of anemia and
      strong association of serum ferritin and transferrin with higher risk of obesity
      or overweight in both metabolic status groups.

PMID- 29224082
TI  - Generating Electric Current by Bioartificial Photosynthesis.
AB  - Abundant solar energy can be a sustainable source of energy. This chapter
      highlights recent advancements, challenges, and future scenarios in bioartificial
      photosynthesis, which is a new subset of bioelectrochemical systems (BESs) and
      technologies. BES technologies exploit the catalytic interactions between
      biological moieties and electrodes. At the nexus of BES and photovoltaics, this
      review focuses on light-harvesting technologies based on bioartificial
      photosynthesis. Such technologies are promising because electrical energy is
      generated from sunlight and water without the need for additional organic
      feedstock. This review focuses on photosynthetic electron generation and transfer
      and compares the current status of bioartificial photosynthesis with other
      artificial systems that mimic the chemistry of photosynthetic energy
      transformation.The fundamental principles and the operation of functional units
      of bioartificial photosynthesis are addressed. Selected photobioelectrochemical
      systems employed to obtain light-driven electric currents from photosynthetic
      organisms are presented. The achievable current output and theoretical maxima are
      revisited by conceptualizing operational and process window techniques. Factors
      affecting overall photocurrent efficiency, performance limitations, and scaleup
      bottlenecks are highlighted in view of enhancing the energy conversion efficiency
      of photobioelectrochemical systems. To finish, the challenges associated with
      bioartificial photosynthetic technologies are outlined. Graphical Abstract
      Operational window for (bio-)artificial photosynthesis. Green circle in the upper
      right corner: development objective for research and engineering efforts.

PMID- 29224083
TI  - Electron Transfer Between Enzymes and Electrodes.
AB  - Efficient electron transfer between redox enzymes and electrocatalytic surfaces
      plays a significant role in development of novel energy conversion devices as
      well as novel reactors for production of commodities and fine chemicals. Major
      application examples are related to enzymatic fuel cells and electroenzymatic
      reactors, as well as enzymatic biosensors. The two former applications are still
      at the level of proof-of-concept, partly due to the low efficiency and obstacles
      to electron transfer between enzymes and electrodes. This chapter discusses the
      theoretical backgrounds of enzyme/electrode interactions, including the main
      mechanisms of electron transfer, as well as thermodynamic and kinetic aspects.
      Additionally, the main electrochemical methods of study are described for
      selected examples. Finally, some recent advancements in the preparation of enzyme
      modified electrodes as well as electrodes for soluble co-factor regeneration are
      reviewed. Graphical Abstract.

PMID- 29224084
TI  - Bipolar dual-lead spinal cord stimulation between two electrodes on the ventral
      and dorsal sides of the spinal cord: consideration of putative mechanisms.
AB  - We have applied bipolar dual-lead spinal cord stimulation (SCS) between two
      cylinder-type electrodes placed on the ventral and dorsal sides of the spinal
      cord (dual-VD-SCS). A 36-year-old man suffered from burning pain from his right
      elbow down to his hand after brachial plexus avulsion. The areas with paresthesia
      induced by conventional SCS did not include the painful hand area. However, dual
      VD-SCS completely induced paresthesia in the painful hand area. We speculate that
      dual-VD-SCS can be applied to stimulate deeper sites of the dorsal column and
      dorsal horn than conventional SCS and is useful for pain reduction.

PMID- 29224085
TI  - Aphasia and cognitive impairment decrease the reliability of rnTMS language
      mapping.
AB  - BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive
      mapping tool to locate functional areas of the brain. While gaining importance in
      the preoperative planning process in motor eloquent regions, its usefulness for
      reliably identifying language areas is still being discussed. The aim of this
      study was to identify biometric factors which might influence and therefore bias
      the results of repetitive nTMS (rnTMS) over cortex areas relevant for language.
      METHOD: We included data of 101 patients with language eloquent brain lesions who
      underwent preoperative rnTMS examination bihemispherically. Prior to rnTMS
      mapping, all patients performed two to three baseline runs of a picture-naming
      paradigm without stimulation, and only promptly and correctly named objects were
      retained for TMS mapping. Nine biometric factors (age, gender, baseline dataset,
      cognitive performance score, aphasia score, histology of lesion, affected
      hemisphere, location of lesion on the hemisphere, pain caused by examination)
      were included in the statistical analysis measuring their correlation with the
      incidence of errors during baseline naming as well as during rnTMS mapping.
      RESULTS: The incidence of baseline errors correlated with aphasia (p < 0.0001)
      and cognitive impairment (p < 0.0001). No significant correlation was observed
      between most biometric factors and errors during rnTMS mapping. Factors
      significantly affecting the incidence of errors during rnTMS mapping were again
      aphasia (p < 0.023) and cognitive impairment (p < 0.038). Patients affected by
      those factors showed a significantly higher baseline error rate, starting at 28%
      error rate. CONCLUSIONS: Patients with pre-existing aphasia or severe cognitive
      impairment did still make significantly more mistakes during rnTMS mapping than
      non-aphasic patients despite baseline stratification, rendering the question of
      whether the procedure is reliable in those patient groups. Baseline testing
      revealed a cut-off point at 28% error rate. Interestingly, age or pain (caused by
      the examination) did not bias the results.

PMID- 29224086
TI  - Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases.
AB  - NLRP3 inflammasome is a key multiprotein signaling platform that tightly controls
      inflammatory responses and coordinates antimicrobial host defenses by activating
      caspase-1 for the subsequent maturation of pro-inflammatory cytokines, IL-1beta
      and IL-18, and induces pyroptosis. The assembly and activation of NLRP3
      inflammasome are linked to the pathogenesis of several cardiovascular disease
      risk factors, such as hypertension and diabetes, and their major consequences
      myocardial remodeling. The study of the NLRP3 inflammasome in these
      cardiovascular disease states may uncover important triggers and endogenous
      modulators of the disease, and lead to new treatment strategies. This review
      outlines current insights into NLRP3 inflammasome research associated with
      cardiovascular diseases and discusses the questions that remain in this field.

PMID- 29224087
TI  - Epidemiology of Gender Differences in Diabetes and Obesity.
AB  - Some aspects of glucose homeostasis and energy balance are regulated differently
      in males and females. This review discusses the most fundamental gender
      differences in diabetes and obesity, including the prevalence of impaired fasting
      glucose and impaired glucose tolerance, the prevalence and incidence of type 2
      and type 1 diabetes, as well as the prevalence of metabolic syndrome and obesity.
      These gender-specific differences in glucose homeostasis and energy balance
      represent a source of factors that should be studied to develop gender-based
      therapeutic avenues for diabetes.

PMID- 29224088
TI  - Sex Differences in Body Composition.
AB  - Body composition differs between men and women. Men have more lean mass, and
      women have more fat mass than men. Men are more likely to accumulate adipose
      tissue around the trunk and abdomen, whereas women usually accumulate adipose
      tissue around the hips and thighs. Less is known about sex differences in ectopic
      fat depots. Advances in imaging allow the noninvasive assessment of abdominal and
      femorogluteal fat compartments, intramyocellular lipids, intrahepatic lipids,
      pericardial adipose tissue, and neck adipose tissue including brown adipose
      tissue and tongue adipose tissue. In this review, sex differences of regional
      adipose tissue, muscle mass, ectopic lipids, and brown adipose tissue and their
      effects on cardiometabolic risk will be discussed. In addition, novel imaging
      techniques to quantify these body composition compartments noninvasively will be
      described.

PMID- 29224089
TI  - Cellular Mechanisms Driving Sex Differences in Adipose Tissue Biology and Body
      Shape in Humans and Mouse Models.
AB  - Sex differences in adipose tissue distribution and the metabolic, endocrine, and
      immune functions of different anatomical fat depots have been described, but they
      are incompletely documented in the literature. It is becoming increasingly clear
      that adipose depots serve distinct functions in males and females and have
      specific physiological roles. However, the mechanisms that regulate the size and
      function of specific adipose tissues in men and women remain poorly understood.
      New insights from mouse models have advanced our understanding of depot
      differences in adipose growth and remodeling via the proliferation and
      differentiation of adipose progenitors that can expand adipocyte number in the
      tissue or simply replace dysfunctional older and larger adipocytes. A limited
      ability of a depot to expand or remodel can lead to excessive adipocyte
      hypertrophy, which is often correlated with metabolic dysfunction. However, the
      relationship of adipocyte size and function varies by depot and sex. For example,
      femoral adipose tissues of premenopausal women appear to have a greater capacity
      for adipose expansion via hyperplasia and hypertrophy; although larger, these
      gluteal-femoral adipocytes remain insulin sensitive. The microenvironment of
      specific depots, including the composition of the extracellular matrix and
      cellular composition, as well as cell-autonomous genetic differences, influences
      sex- and depot-dependent metabolic and growth properties. Although there are some
      species differences, studies of the molecular and physiological determinants of
      sex differences in adipocyte growth and function in humans and rodents are both
      needed for understanding sex differences in health and disease.

PMID- 29224090
TI  - Men Are from Mars, Women Are from Venus: Sex Differences in Insulin Action and
      Secretion.
AB  - Sex difference plays a substantial role in the regulation of glucose metabolism
      in healthy glucose-tolerant humans. The factors which may contribute to the sex
      related differences in glucose metabolism include differences in lifestyle (diet
      and exercise), sex hormones, and body composition. Several epidemiological and
      observational studies have noted that impaired glucose tolerance is more common
      in women than men. Some of these studies have attributed this to differences in
      body composition, while others have attributed impaired insulin sensitivity as a
      cause of impaired glucose tolerance in women. We studied postprandial glucose
      metabolism in 120 men and 90 women after ingestion of a mixed meal. Rates of meal
      glucose appearance, endogenous glucose production, and glucose disappearance were
      calculated using a novel triple-tracer isotope dilution method. Insulin action
      and secretion were calculated using validated physiological models. While rate of
      meal glucose appearance was higher in women than men, rates of glucose
      disappearance were higher in elderly women than elderly men while young women had
      lower rates of glucose disappearance than young men. Hence, sex has an impact on
      postprandial glucose metabolism, and sex differences in carbohydrate metabolism
      may have important implications for approaches to prevent and manage diabetes in
      an individual.

PMID- 29224091
TI  - The Role of Sex and Sex Hormones in Regulating Obesity-Induced Inflammation.
AB  - Metabolic and non-metabolic complications due to obesity are becoming more
      prevalent, yet our understanding of the mechanisms driving these is not. This is
      due to individual risk factor variability making it difficult to predict disease
      outcomes such as diabetes and insulin resistance. Gender is a critical factor in
      obesity outcomes with women having more adiposity but reduced metabolic
      complications compared to men. The role of immune system activation during
      obesity is an emerging field that links adiposity to metabolic syndrome.
      Furthermore, evidence from animal models suggests that sex differences exist in
      immune responses and, therefore, could be a possible mechanism leading to sex
      differences in metabolic disease. While there is still much to learn in the area
      of sex-differences research, this chapter will review the current knowledge and
      literature detailing the role of sex and sex hormones on adiposity and
      metabolically induced inflammation in obesity.

PMID- 29224092
TI  - Sex Differences in Leptin Control of Cardiovascular Function in Health and
      Metabolic Diseases.
AB  - Leptin, the adipocyte-derived hormone identified in 1994 for its major role in
      the control of satiety and body weight regulation, is an adipokine secreted in a
      sex-specific manner. Although it has clearly been established that females
      secrete three to four times more leptin than males and that this sexual
      dimorphism in leptin secretion is exacerbated with overweight and obesity, the
      origin and the physiological consequences of this sexual dimorphism remain ill
      defined. The adipose tissue is the major site of leptin secretion; however,
      leptin receptors are ubiquitously expressed, conferring to leptin, and indirectly
      to the adipose tissue, a potential role in the control of numerous physiological
      functions. Besides its major role in the control of food intake and energy
      expenditure, leptin has been shown to contribute to the control of immune, bone,
      reproductive, and cardiovascular functions. The goal of the present chapter is to
      review and discuss the current knowledge on the contribution of leptin to the
      control of cardiovascular function while focusing on the impact of the sexual
      dimorphism in leptin secretion and of the pathological increases in leptin levels
      induced by overweight and obesity.

PMID- 29224093
TI  - Sex Effects at the Ramparts: Nutrient- and Microbe-Mediated Regulation of the
      Immune-Metabolic Interface.
AB  - The relationships between dietary compounds, derivative metabolites, and host
      metabolism and immunity are controlled by diverse molecular mechanisms. Essential
      contributions to these dynamics come from the community of microbes (the
      microbiome) inhabiting the human digestive tract. The composition and function of
      the microbiome are shaped by available nutrients, and reciprocally, these
      organisms produce an as yet poorly defined repertoire of molecules that
      communicate with the epithelial barrier and the mucosal immune system. We present
      evidence that diet-derived vitamins and lipids regulate immunity and metabolic
      function and highlight the diverse mechanisms through which these effects are
      impacted by sex. We discuss exciting new data emerging from studies using high
      throughput sequencing technology, specialized mouse models, and bio-specimens,
      and clinical data from human subjects that have begun to reveal the complexity of
      these interactions. Also profiled in this chapter are the striking sex
      differences in pathways by which dietary nutrients and gut microbes modify
      metabolism, immunity, and immune- and inflammation-mediated diseases. Although
      the incidence, severity, and therapeutic responses of many autoimmune diseases
      differ by sex, the molecular mechanisms of these effects remain poorly
      understood.

PMID- 29224094
TI  - Sexual Dimorphism and Estrogen Action in Mouse Liver.
AB  - Recent studies have demonstrated that in mice, the estrogen receptor alpha
      (ERalpha) is expressed in the liver and has a direct effect on the regulation of
      the hepatic genes relevant for energy metabolism and drug metabolism. The sex
      related differential expression of the hepatic ERalpha raises the questions as to
      whether this receptor is responsible for the sexual differences observed in the
      physiopathology of the liver.

PMID- 29224095
TI  - Sex Differences in Muscle Wasting.
AB  - With aging and other muscle wasting diseases, men and women undergo similar
      pathological changes in skeletal muscle: increased inflammation, enhanced
      oxidative stress, mitochondrial dysfunction, satellite cell senescence, elevated
      apoptosis and proteasome activity, and suppressed protein synthesis and myocyte
      regeneration. Decreased food intake and physical activity also indirectly
      contribute to muscle wasting. Sex hormones also play important roles in
      maintaining skeletal muscle homeostasis. Testosterone is a potent anabolic factor
      promoting muscle protein synthesis and muscular regeneration. Estrogens have a
      protective effect on skeletal muscle by attenuating inflammation; however, the
      mechanisms of estrogen action in skeletal muscle are less well characterized than
      those of testosterone. Age- and/or disease-induced alterations in sex hormones
      are major contributors to muscle wasting. Hence, men and women may respond
      differently to catabolic conditions because of their hormonal profiles. Here we
      review the similarities and differences between men and women with common wasting
      conditions including sarcopenia and cachexia due to cancer, end-stage renal
      disease/chronic kidney disease, liver disease, chronic heart failure, and chronic
      obstructive pulmonary disease based on the literature in clinical studies. In
      addition, the responses in men and women to the commonly used therapeutic agents
      and their efficacy to improve muscle mass and function are also reviewed.

PMID- 29224096
TI  - Origins and Functions of the Ventrolateral VMH: A Complex Neuronal Cluster
      Orchestrating Sex Differences in Metabolism and Behavior.
AB  - The neuroendocrine brain or hypothalamus has emerged as one of the most highly
      sexually dimorphic brain regions in mammals, and specifically in rodents. It is
      not surprising that hypothalamic nuclei play a pivotal role in controlling sex
      dependent physiology. This brain region functions as a chief executive officer or
      master regulator of homeostatic physiological systems to integrate both external
      and internal signals. In this review, we describe sex differences in energy
      homeostasis that arise in one area of the hypothalamus, the ventrolateral
      subregion of the ventromedial hypothalamus (VMHvl) with a focus on how male and
      female neurons function in metabolic and behavioral aspects. Because other
      chapters within this book provide details on signaling pathways in the VMH that
      contribute to sex differences in metabolism, our discussion will be limited to
      how the sexually dimorphic VMHvl develops and what key regulators are thought to
      control the many functional and physiological endpoints attributed to this
      region. In the last decade, several exciting new studies using state-of-the-art
      genetic and molecular tools are beginning to provide some understanding as to how
      specific neurons contribute to the coordinated physiological responses needed by
      male and females. New technology that combines intersectional spatial and genetic
      approaches is now allowing further refinement in how we describe, probe, and
      manipulate critical male and female neurocircuits involved in metabolism.

PMID- 29224097
TI  - Menopause, Estrogens, and Glucose Homeostasis in Women.
AB  - Randomized trials suggest that menopausal hormone therapy (MHT) prevents type 2
      diabetes. Still, the mechanisms of these antidiabetic effects are a matter of
      controversy. This chapter provides an analysis of epidemiological and clinical
      evidence and proposes a mechanism for the effect of menopause and MHT on type 2
      diabetes development and prevention. It discusses the beneficial role of
      estradiol on glucose homeostasis that is lost at menopause and improved by MHT,
      which delays type 2 diabetes. This chapter aims to reconcile differences among
      studies of the effect of menopause and MHT formulations on type 2 diabetes and
      argues that discrepancies arise from physiological differences in methods used to
      assess glucose homeostasis.

PMID- 29224099
TI  - The Role of Skeletal Muscle Estrogen Receptors in Metabolic Homeostasis and
      Insulin Sensitivity.
AB  - Women in the modern era are challenged with facing menopausal symptoms as well as
      heightened disease risk associated with increasing adiposity and metabolic
      dysfunction for up to three decades of life. Treatment strategies to combat
      metabolic dysfunction and associated pathologies have been hampered by our lack
      of understanding regarding the biological causes of these clinical conditions and
      our incomplete understanding regarding the effects of estrogens and the tissue
      specific functions and molecular actions of its receptors. In this chapter we
      provide evidence supporting a critical and protective role for skeletal muscle
      estrogen receptor alpha in the maintenance of metabolic homeostasis and insulin
      sensitivity. Studies identifying the critical ER-regulated pathways essential for
      disease prevention will lay the important foundation for the rational design of
      novel therapeutic strategies to improve the health of women while limiting
      secondary complications that have plagued traditional hormone replacement
      interventions.

PMID- 29224098
TI  - Role of Estrogens in the Regulation of Liver Lipid Metabolism.
AB  - Before menopause, women are protected from atherosclerotic heart disease
      associated with obesity relative to men. Sex hormones have been proposed as a
      mechanism that differentiates this risk. In this review, we discuss the
      literature around how the endogenous sex hormones and hormone treatment
      approaches after menopause regulate fatty acid, triglyceride, and cholesterol
      metabolism to influence cardiovascular risk.The important regulatory functions of
      estrogen signaling pathways with regard to lipid metabolism have been in part
      obscured by clinical trials with hormone treatment of women after menopause, due
      to different formulations, routes of delivery, and pairings with progestins. Oral
      hormone treatment with several estrogen preparations increases VLDL triglyceride
      production. Progestins oppose this effect by stimulating VLDL clearance in both
      humans and animals. Transdermal estradiol preparations do not increase VLDL
      production or serum triglycerides.Many aspects of sex differences in
      atherosclerotic heart disease risk are influenced by the distributed actions of
      estrogens in the muscle, adipose, and liver. In humans, 17beta-estradiol (E2) is
      the predominant circulating estrogen and signals through estrogen receptor alpha
      (ERalpha), estrogen receptor beta (ERbeta), and G-protein-coupled estrogen
      receptor (GPER). Over 1000 human liver genes display a sex bias in their
      expression, and the top biological pathways are in lipid metabolism and genes
      related to cardiovascular disease. Many of these genes display variation
      depending on estrus cycling in the mouse. Future directions will likely rely on
      targeting estrogens to specific tissues or specific aspects of the signaling
      pathways in order to recapitulate the protective physiology of premenopause
      therapeutically after menopause.

PMID- 29224101
TI  - Estradiol Regulation of Brown Adipose Tissue Thermogenesis.
AB  - Physiologically, estrogens carry out a myriad of functions, the most essential
      being the regulation of the reproductive axis. Currently, it is also dogmatic
      that estrogens play an important role modulating energy balance and metabolism.
      In this sense, it is well known that low estrogens levels, occurring due to
      ovarian insufficiency, in conditions such as menopause or ovariectomy (OVX), are
      associated with increased food intake and decreased energy expenditure, leading
      to weight gain and obesity at long term. Concerning energy expenditure, the main
      effect of estradiol (E2) is on brown adipose tissue (BAT) thermogenesis. Thus,
      acting through a peripheral or a central action, E2 activates brown fat activity
      and increases body temperature, which is negatively associated with body weight.
      Centrally, the hypothalamic AMP-activated protein kinase (AMPK) mediates the E2
      action on BAT thermogenesis. In this chapter, we will summarize E2 regulation of
      BAT thermogenesis and how this can influence energy balance and metabolism in
      general.

PMID- 29224102
TI  - Brain Estrogens and Feeding Behavior.
AB  - Estrogens play essential roles in suppressing food intake and preventing body
      weight gain. Tremendous research efforts have been focused on estrogen physiology
      in the context of feeding control. Estrogen receptors and the related signals
      have been attractive targets for development of new obesity therapies. This
      chapter focuses on the functional interactions between brain estrogens and other
      appetite-regulatory signals, the critical estrogen receptor isoforms and distinct
      brain regions that mediate effects of estrogens on feeding, and the intracellular
      signals that are involved.

PMID- 29224100
TI  - Estrogens and Body Weight Regulation in Men.
AB  - Our understanding of the metabolic roles of sex steroids in men has evolved
      substantially over recent decades. Whereas testosterone once was believed to
      contribute to metabolic risk in men, the importance of adequate androgen exposure
      for the maintenance of metabolic health has been demonstrated unequivocally. A
      growing body of evidence now also supports a critical role for estrogens in
      metabolic regulation in men. Recent data from clinical intervention studies
      indicate that estradiol may be a stronger determinant of adiposity than
      testosterone in men, and even short-term estradiol deprivation contributes to fat
      mass accrual. The following chapter will outline findings to date regarding the
      mechanisms, whereby estrogens contribute to the regulation of body weight and
      adiposity in men. It will present emergent clinical data as well as preclinical
      findings that reveal mechanistic insights into estrogen-mediated regulation of
      body composition. Findings in both males and females will be reviewed, to draw
      comparisons and to highlight knowledge gaps regarding estrogen action
      specifically in males. Finally, the clinical relevance of estrogen exposure in
      men will be discussed, particularly in the context of a rising global prevalence
      of obesity and expanding clinical use of sex steroid-based therapies in men.

PMID- 29224103
TI  - Sex Differences and Role of Estradiol in Hypoglycemia-Associated Counter
      Regulation.
AB  - Vital nerve cell functions, including maintenance of transmembrane voltage and
      information transfer, occur at high energy expense. Inadequate provision of the
      obligate metabolic fuel glucose exposes neurons to risk of dysfunction or injury.
      Clinical hypoglycemia rarely occurs in nondiabetic individuals but is an
      unfortunate regular occurrence in patients with type 1 or advanced insulin
      treated type 2 diabetes mellitus. Requisite strict glycemic control, involving
      treatment with insulin, sulfonylureas, or glinides, can cause frequent episodes
      of iatrogenic hypoglycemia due to defective counter-regulation, including reduced
      glycemic thresholds and diminished magnitude of motor responses. Multiple
      components of the body's far-reaching energy balance regulatory network,
      including the hindbrain dorsal vagal complex, provide dynamic readout of cellular
      energetic disequilibrium, signals that are utilized by the hypothalamus to shape
      counterregulatory autonomic, neuroendocrine, and behavioral outflow toward
      restoration of glucostasis. The ovarian steroid hormone 17beta-estradiol acts on
      central substrates to preserve nerve cell energy stability brain-wide, thereby
      providing neuroprotection against bio-energetic insults such as neurodegenerative
      diseases and acute brain ischemia. The current review highlights recent evidence
      implicating estrogen in gluco-regulation in females by control of hindbrain
      metabolic sensor screening and signaling of hypoglycemia-associated neuro
      energetic instability. It is anticipated that new understanding of the
      mechanistic basis of how estradiol influences metabolic sensory input from this
      critical brain locus to discrete downstream regulatory network substrates will
      likely reveal viable new molecular targets for therapeutic simulation of hormone
      actions that promote positive neuronal metabolic state during acute and recurring
      hypoglycemia.

PMID- 29224104
TI  - The Role of Estrogens in Pancreatic Islet Physiopathology.
AB  - In rodent models of insulin-deficient diabetes, 17beta-estradiol (E2) protects
      pancreatic insulin-producing beta-cells against oxidative stress, amyloid
      polypeptide toxicity, gluco-lipotoxicity, and apoptosis. Three estrogen receptors
      (ERs)-ERalpha, ERbeta, and the G protein-coupled ER (GPER)-have been identified
      in rodent and human beta-cells. This chapter describes recent advances in our
      understanding of the role of ERs in islet beta-cell function, nutrient
      homeostasis, survival from pro-apoptotic stimuli, and proliferation. We discuss
      why and how ERs represent potential therapeutic targets for the maintenance of
      functional beta-cell mass.

PMID- 29224105
TI  - Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the
      Regulation of Energy and Glucose Homeostasis.
AB  - Estrogen receptor alpha (ERalpha) has been demonstrated to play a key role in
      reproduction but also to exert numerous functions in nonreproductive tissues.
      Accordingly, ERalpha is now recognized as a key regulator of energy homeostasis
      and glucose metabolism and mediates the protective effects of estrogens against
      obesity and type 2 diabetes. This chapter attempts to summarize our current
      understanding of the mechanisms of ERalpha activation and their involvement in
      the modulation of energy balance and glucose metabolism. We first focus on the
      experimental studies that constitute the basis of the understanding of ERalpha as
      a nuclear receptor and more specifically on the key roles played by its two
      activation functions (AFs). We depict the consequences of the selective
      inactivation of these AFs in mouse models, which further underline the prominent
      role of nuclear ERalpha in the prevention of obesity and diabetes, as on the
      reproductive tract and the vascular system. Besides these nuclear actions, a
      fraction of ERalpha is associated with the plasma membrane and activates
      nonnuclear signaling from this site. Such rapid effects, called membrane
      initiated steroid signals (MISS), have been characterized in a variety of cell
      lines and in particular in endothelial cells. The development of selective
      pharmacological tools that specifically activate MISS as well as the generation
      of mice expressing an ERalpha protein impeded for membrane localization has just
      begun to unravel the physiological role of MISS in vivo and their contribution to
      ERalpha-mediated metabolic protection. Finally, we discuss novel perspectives for
      the design of tissue-selective ER modulators.

PMID- 29224106
TI  - G-Protein-Coupled Estrogen Receptor (GPER) and Sex-Specific Metabolic
      Homeostasis.
AB  - Obesity and metabolic syndrome display disparate prevalence and regulation
      between males and females. Human, as well as rodent, females with regular
      menstrual/estrous cycles exhibit protection from weight gain and associated
      chronic diseases. These beneficial effects are predominantly attributed to the
      female hormone estrogen, specifically 17beta-estradiol (E2). E2 exerts its
      actions via multiple receptors, nuclear and extranuclear estrogen receptor (ER)
      alpha and ERbeta, and the G-protein-coupled estrogen receptor (GPER, previously
      termed GPR30). The roles of GPER in metabolic homeostasis are beginning to emerge
      but are complex and remain unclear. The discovery of GPER-selective
      pharmacological agents (agonists and antagonists) and the availability of GPER
      knockout mice have significantly enhanced our understanding of the functions of
      GPER in normal physiology and disease. GPER action manifests pleiotropic effects
      in metabolically active tissues such as the pancreas, adipose, liver, and
      skeletal muscle. Cellular and animal studies have established that GPER is
      involved in the regulation of body weight, feeding behavior, inflammation, as
      well as glucose and lipid homeostasis. GPER deficiency leads to increased
      adiposity, insulin resistance, and metabolic dysfunction in mice. In contrast,
      pharmacologic stimulation of GPER in vivo limits weight gain and improves
      metabolic output, revealing a promising novel therapeutic potential for the
      treatment of obesity and diabetes.

PMID- 29224107
TI  - Sex-Dependent Role of Estrogen Sulfotransferase and Steroid Sulfatase in
      Metabolic Homeostasis.
AB  - Sulfonation and desulfation are two opposing processes that represent an
      important layer of regulation of estrogenic activity via ligand supplies.
      Enzymatic activities of families of enzymes, known as sulfotransferases and
      sulfatases, lead to structural and functional changes of the steroids, thyroids,
      xenobiotics, and neurotransmitters. Estrogen sulfotransferase (EST) and steroid
      sulfatase (STS) represent negative and positive regulation of the estrogen
      activity, respectively. This is because EST-mediated sulfation deactivates
      estrogens, whereas STS-mediated desulfation converts the inactive estrogen
      sulfates to active estrogens. In addition to the known functions of estrogens,
      EST and STS in reproductive processes, regulation of estrogens and other signal
      molecules especially at the local tissue levels has gained increased attention in
      the context of metabolic disease in recent years. EST expression is detectable in
      the subcutaneous adipose tissue in both obese women and men, and the expression
      of EST is markedly induced in the livers of rodent models of obesity and type 2
      diabetes. STS was found to be upregulated in patients with chronic inflammatory
      liver diseases. Interestingly, the tissue distribution and the transcriptional
      regulation of EST and STS exhibit obvious sex and species specificity. EST
      ablation produces completely opposite metabolic phenotype in female and male
      obese mice. Adipogenesis is also differentially regulated by EST in murine and
      human adipocytes. This chapter focuses on the recent progress in our
      understanding of the expression and regulation EST and STS in the context of
      metabolic homeostasis.

PMID- 29224108
TI  - Negative Impact of Testosterone Deficiency and 5alpha-Reductase Inhibitors
      Therapy on Metabolic and Sexual Function in Men.
AB  - Androgens are steroid hormones with pleotropic and diverse biochemical and
      physiological functions, and androgen deficiency exerts a negative impact on
      human health. Testosterone (T) either directly or via its transformation into the
      more potent metabolite 5alpha-dihydrotestosterone (5alpha-DHT) or via
      aromatization into estradiol (E2) modulates important biochemical signaling
      pathways of human physiology and plays a critical role in the growth and/or
      maintenance of functions in a host of tissues and organs. T and 5alpha-DHT play
      an important role in regulating physiology of the muscle, adipose tissue, liver,
      bone, and central nervous system, as well as reproductive and sexual functions.
      Thus, androgen deficiency (also referred to as hypogonadism) is a well-recognized
      medical condition and if remained untreated will have a negative impact on human
      health and quality of life.In this chapter, we have summarized the negative
      impact of T deficiency (TD) on a host of physiological functions including
      reduced lean body mass (LBM), increased fat mass (FM), increased insulin
      resistance (IR), metabolic syndrome (MetS) and adiposity, reduced bone mineral
      density (BMD), anemia, sexual dysfunction, and reduced quality of life and
      increased mortality. In addition, we discuss another critical aspect of
      unrecognized form of androgen deficiency resulting from inhibition of 5alpha
      reductases with drugs, such as finasteride and dutasteride, to block
      transformation of T into 5alpha-DHT in the course of treatment of benign
      prostatic hyperplasia (BPH) and male pattern hair loss, also known as
      androgenetic alopecia (AGA). The negative impact of drugs that inhibit
      transformation of T to 5alpha-DHT by 5alpha-reductases on metabolic function is
      manifested in fat accumulation in the liver, which may predispose to nonalcoholic
      fatty liver disease (NAFLD). Also, inhibition of 5alpha-DHT formation increases
      glucose synthesis and reduces glucose disposal potentially contributing to
      hyperglycemia, IR, and elevated activities of liver function enzymes concomitant
      with reduction in circulating T levels, worsening erectile dysfunction (ED), and
      reduced quality of life.Although we have attempted to summarize the current
      literature pertaining to this critical topic "androgen deficiency" and its impact
      on men's health and quality of life, there remain many gaps in the knowledge
      regarding the biochemical pathways that are involved in the pathophysiology of
      androgen deficiency. We wish to clearly state that there are areas of
      controversies, including whether age-related androgen deficiency (functional
      hypogonadism) merits treatment and whether T therapy provided real proven
      benefits. Finally, considerable debate exists with respect to the potential and
      purported cardiovascular (CV) risks of treating TD with exogenous T. For brevity
      sake, we will not discuss in detail the benefits of T therapy in men with TD
      since this topic is comprehensively covered by Dr. F. Saad's chapter in this
      book, entitled "Testosterone Therapy and Glucose Homeostasis in Men with
      Testosterone Deficiency (Hypogonadism)."We have made a concerted effort to
      address the controversy of T therapy in men with TD in the discussion. However,
      we wish to acknowledge that these issues will remain a matter of debate for some
      time to come. Only with advances in fundamental basic science and clinical
      research, some of these controversial issues may be laid to rest. Nevertheless,
      we believe that there is considerable body of credible evidence to suggest that T
      therapy of men with TD is safe and effective and provides a host of health
      benefits and therefore merits considerations in men with TD, irrespective of the
      underlying cause or etiology. An additional aspect of androgen deficiency is the
      drug-induced reduction in 5alpha-DHT levels by the use of 5alpha-reductase
      inhibitors. We also believe that physicians prescribing 5alpha-reductase
      inhibitors (i.e., finasteride or dutasteride) for relief of BPH symptoms or
      treatment of hair loss should engage their patients in a productive discussion
      regarding the potential adverse side effects of these medications on their
      overall health and quality of life.

PMID- 29224109
TI  - Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency
      (Hypogonadism).
AB  - Since the early 1990s, it has been recognized that testosterone (T) levels are
      lower in men with type 2 diabetes mellitus (T2DM) compared with nondiabetic men
      (controls). Hypogonadism has been reported in approximately 50% of men with T2DM
      with robust correlations with measures of obesity, such as waist circumference
      and body mass index (BMI). In longitudinal studies, hypogonadism has been
      identified as a predictor of incident T2DM. Experimental withdrawal of T led to
      acute decreased insulin sensitivity, which can be reversed by normalization of T
      concentrations. Androgen deprivation therapy, commonly used in men with advanced
      prostate cancer, increases the risk of incident T2DM significantly.While short
      term studies of T therapy in hypogonadal men with T2DM show only minor effects,
      long-term administration of T leads to meaningful and sustained improvements of
      glycemic control with parallel reductions in body weight and waist circumference.
      The more insulin-resistant and obese a patient is at the time of initiation of T
      therapy, the more improvements are noted. The observed effects are likely
      mediated by the increase in lean body mass invariably achieved by T therapy, as
      well as the improvement in energy and motivation, referred to as the psychotropic
      effects of T. As recommended by various guidelines, measuring T levels and, if
      indicated, restoring men's T levels into the normal physiological range can have
      a substantial impact on ameliorating T2DM in hypogonadal men.

PMID- 29224111
TI  - Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep.
AB  - Insulin resistance, a common feature of metabolic disorders such as obesity,
      nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary
      syndrome, is a risk factor for development of diabetes. Because sex hormones
      orchestrate the establishment of sex-specific behavioral, reproductive, and
      metabolic differences, a role for them in the developmental origin of insulin
      resistance is also to be expected. Female sheep exposed to male levels of
      testosterone during fetal life serve as an excellent translational model for
      delineating programming of insulin resistance. This chapter summarizes the
      ontogeny of insulin resistance, the tissue-specific changes in insulin
      sensitivity, and the various factors that are involved in the programming and
      maintenance of the insulin resistance in adult female sheep that were
      developmentally exposed to fetal male levels of testosterone during the sexual
      differentiation window.

PMID- 29224110
TI  - Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates.
AB  - The in-depth characterization of sex differences relevant to human physiology
      requires the judicious use of a variety of animal models and human clinical data.
      Nonhuman primates (NHPs) represent an important experimental system that bridges
      rodent studies and clinical investigations. NHP studies have been especially
      useful in understanding the role of sex hormones in development and metabolism
      and also allow the elucidation of the effects of pertinent dietary influences on
      physiology pertinent to disease states such as obesity and diabetes. This chapter
      summarizes the current state of our understanding of androgen effects on male and
      female NHP metabolism relevant to hypogonadism in human males and polycystic
      ovary syndrome in human females. This review will also focus on the interaction
      between altered androgen levels and dietary restriction and excess, in particular
      the Western-style diet that underlies significant human pathophysiology.

PMID- 29224112
TI  - The Role of Androgen Excess in Metabolic Dysfunction in Women : Androgen Excess
      and Female Metabolic Dysfunction.
AB  - Polycystic ovary syndrome (PCOS) is characterized by the association of androgen
      excess with chronic oligoovulation and/or polycystic ovarian morphology, yet
      metabolic disorders and classic and nonclassic cardiovascular risk factors
      cluster in these women from very early in life. This chapter focuses on the
      mechanisms underlying the association of PCOS with metabolic dysfunction,
      focusing on the role of androgen excess on the development of visceral adiposity
      and adipose tissue dysfunction.

PMID- 29224113
TI  - Sex, Gender, and Transgender: Metabolic Impact of Cross Hormone Therapy.
AB  - Most preclinical and clinical, animal, and human research has been biased with
      respect to sex and even more so with respect to gender. In fact, little is known
      about the impact of sex and even less about the influence of gender on overall
      metabolic processes. The National Institutes of Health has recognized this gap in
      scientific knowledge and now mandates that studies be conducted in both sexes and
      to include gender as variables influencing physiological processes such as
      metabolism. It is therefore critical to understand and appreciate how to
      incorporate sex and gender in preclinical and clinical research in order to
      enhance our understanding of the mechanisms by which metabolic processes differ
      by sex and gender. In this chapter, we define sex and gender and discuss when sex
      and gender are not aligned, such as that which occurs in transgender individuals,
      and how this impacts metabolic processes. We discuss the importance of
      understanding the influence and interactions between sex hormones and sex
      chromosomes rather than focusing on their relative contributions to metabolism in
      isolation. This knowledge will optimize therapies specific for individuals which
      need to encompass sex and gender.

PMID- 29224114
TI  - Coated-Platelet Trends Predict Short-Term Clinical OutcomeAfter Subarachnoid
      Hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high socio-economic
      burden. Prothrombotic states of early brain injury (EBI) and delayed cerebral
      ischemia (DCI) after aSAH determine morbidity and mortality. To understand how
      activated platelets might contribute to such prothrombotic states, we studied
      trends in coated-platelets during EBI and DCI periods. Serial blood samples from
      a prospective cohort of aSAH patients were collected and assayed for coated
      platelet levels. Patient's coated-platelet level during post-hospital discharge
      follow-up served as an estimate of baseline. Occurrence of DCI, Montreal
      cognitive assessment (MOCA) score of < 26, and modified Rankin scale (mRS) of 3-6
      were considered poor clinical outcomes. Non-linear regression analysis detected a
      transition between periods of rising and declining coated-platelet levels at day
      4. Additional regression analyses of coated-platelet trends before day 4 showed
      differences among patients with modified Fisher 3-4 [4.2% per day (95% CI 2.4,
      6.1) vs. - 0.8% per day (95% CI - 3.4, 1.8); p = 0.0023] and those developing DCI
      [4.6% per day (95% CI 2.8, 6.5) vs. - 1.9% per day (95% CI - 4.5, 0.5); p <
      0.001]. Differences between peak coated-platelet levels and baseline levels were
      larger, on average for those with DCI [18.1 +/- 9.6 vs. 10.6 +/- 8.0; p = 0.03],
      MOCA < 26 [17.0 +/- 7.8 vs. 10.7 +/- 7.4; p = 0.05] and mRS 3-6 [24.8 +/- 10.5
      vs. 11.9 +/- 7.6; p = 0.01]. Coated-platelet trends after aSAH predict DCI and
      short-term clinical outcomes. The degree of rise in coated-platelets is also
      associated with adverse clinical outcomes.

PMID- 29224115
TI  - CT features for diagnosing acute torsion of uterine subserosal leiomyoma.
AB  - PURPOSE: To evaluate the usefulness of computed tomographic (CT) features for
      identifying acute torsion of uterine subserosal leiomyoma (USL). SUBJECTS AND
      METHODS: We analyzed contrast-enhanced CT examinations of 7 USLs with torsion and
      44 USLs without torsion. Two radiologists evaluated the CT features, which
      consisted of poor contrast enhancement inside the USL, thin rim enhancement
      around the USL, calcification within the USL, a beak sign between the uterus and
      USL, fan-shaped poor contrast enhancement in the uterus area adjacent to the USL
      (dark fan sign), and ascites. We analyzed the frequencies of these CT features in
      the USLs with versus without torsion using Fisher's exact test. RESULTS: The
      respective frequencies of CT features in USLs with and without torsion were as
      follows: poor contrast enhancement, 86 and 5% (P = 0.001); thin rim enhancement,
      71 and 9% (P = 0.001); calcification, 29 and 18% (P = 0.61); beak sign, 57 and
      86% (P = 0.10); dark fan sign, 57 and 0% (P = 0.001); and ascites, 100 and 20% (P
      = 0.01). CONCLUSIONS: The CT features of poor contrast enhancement, thin rim
      enhancement, and dark fan sign are valuable for identifying acute torsion of USL.

PMID- 29224116
TI  - Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.
AB  - Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules
      involved in regulating the activity of many proteins such as tyrosine kinases and
      phosphatases by respective recognition of phosphotyrosine and proline-rich
      regions. In the Src family kinases, the inactive state of the protein is the
      direct result of the interaction of the SH2 and the SH3 domain with intra
      molecular regions, leading to a closed structure incompetent with substrate
      modification. Here, we report the 1H, 15N and 13C backbone- and side-chain
      chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and
      structural differences between tandem and single domains. The BMRB accession
      number is 27165.

PMID- 29224117
TI  - Heated communities: large inter- and intraspecific variation in heat tolerance
      across trophic levels of a soil arthropod community.
AB  - Temperature extremes are predicted to increase in frequency, intensity and
      duration under global warming and are believed to significantly affect community
      composition and functioning. However, the effect of extreme climatic events on
      communities remains difficult to predict, especially because species can show
      dissimilar responses to abiotic changes, which may affect the outcome of species
      interactions. To anticipate community responses we need knowledge on within and
      among species variation in stress tolerance. We exposed a soil arthropod
      community to experimental heat waves in the field and measured heat tolerance of
      species of different trophic levels from heated and control plots. We measured
      the critical thermal maximum (CTmax) of individuals to estimate inter- and
      intraspecific variation in heat tolerance in this community, and how this was
      affected by experimental heat waves. We found interspecific variation in heat
      tolerance, with the most abundant prey species, the springtail Isotoma riparia,
      being more sensitive to high temperatures than its predators (various spider
      species). Moreover, intraspecific variation in CTmax was substantial, suggesting
      that individuals within a single species were unequally affected by heat
      extremes. However, heat tolerance of species did not increase after being exposed
      to an experimental heat wave. We conclude that interspecific variation in
      tolerance traits potentially causes trophic mismatches during extreme events, but
      that intraspecific variation could lessen these effects by enabling partial
      survival of populations. Therefore, ecophysiological traits can provide a better
      understanding of abiotic effects on communities, not only within taxonomic or
      functional groups, but also when comparing different trophic levels.

PMID- 29224118
TI  - Testing the hypothesis of hierarchical predictability in ecological restoration
      and succession.
AB  - To advance predictive ecology, the hypothesis of hierarchical predictability
      proposes that community measures for which species are interchangeable (e.g.,
      structure and species richness) are more predictable than measures for which
      species identity matters (e.g., community composition). Predictability is
      hypothesized to decrease for response measures in order of the following
      categories: structure, species richness, function, and species composition. We
      tested this hypothesis using a 14-year, oak savanna-prairie restoration
      experiment that removed non-native pine plantations at 24 sites in northwestern
      Ohio, USA. Based on 24 response measures, the data showed minimal support for the
      hypothesis, because response measures varied in predictability within categories.
      Half of response measures had over half their variability modeled using fixed
      (restoration treatment and year) and random plot effects, and these "predictable"
      measures occurred in all four categories. Pine basal area, environment (e.g.,
      soil texture), and antecedent vegetation accounted for over half the variation in
      change within the first three post-restoration years for 77% of response
      measures. Change between the 3rd and 14th years was less predictable, but most
      restoration measures increased favorably via sites achieving them in unique ways.
      We propose that variation will not conform with the hypothesis of hierarchical
      predictability in ecosystems with vegetation dynamics driven by stochastic
      processes such as seed dispersal, or where vegetation structure and species
      richness are influenced by species composition. The ability to predict a
      community measure may be more driven by the number of combinations of casual
      factors affecting a measure than by the number of values it can have.

PMID- 29224119
TI  - Effects of diurnal temperature range on mortality in Hefei city, China.
AB  - Although several studies indicated an association between diurnal temperature
      range (DTR) and mortality, the results about modifiers are inconsistent, and few
      studies were conducted in developing inland country. This study aims to evaluate
      the effects of DTR on cause-specific mortality and whether season, gender, or age
      might modify any association in Hefei city, China, during 2007-2016. Quasi
      Poisson generalized linear regression models combined with a distributed lag non
      linear model (DLNM) were applied to evaluate the relationships between DTR and
      non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped
      relationship between DTR and cause-specific mortality. With a DTR of 8.3  degrees
      C as the reference, the cumulative effects of extremely high DTR were
      significantly higher for all types of mortality than effects of lower or moderate
      DTR in full year. When stratified by season, extremely high DTR in spring had a
      greater impact on all cause-specific mortality than other three seasons. Male and
      the elderly (>= 65 years) were consistently more susceptible to extremely high
      DTR effect than female and the youth (< 65 years) for non-accidental and
      cardiovascular mortality. To the contrary, female and the youth were more
      susceptible to extremely high DTR effect than male and the elderly for
      respiratory morality. The study suggests that extremely high DTR is a potential
      trigger for non-accidental mortality in Hefei city, China. Our findings also
      highlight the importance of protecting susceptible groups from extremely high DTR
      especially in the spring.

PMID- 29224120
TI  - Spontaneous cervical artery dissection is accompanied by a hypercoagulable state
      and simultaneous inflammatory condition.
AB  - BACKGROUND: Spontaneous cervical artery dissections (sCAD) are often preceded by
      infections. However, existing data about inflammatory parameters remained
      inconsistent. Remarkably, concurrent information about the coagulation system,
      whose affection seems also reasonable to cause ischaemic events, are still
      lacking in sCAD patients. Thus, this study explores the association between the
      inflammatory and coagulation system in patients with sCAD. METHODS: The
      parameters leukocyte and thrombocyte count, C-reactive protein, fibrinogen, D
      dimer, activated partial thromboplastin time (aPTT) and prothrombin time were
      extracted from hospital-based medical records of patients (n = 60) with sCAD and
      compared with those of a control group (n = 97) from a prospective observational
      stroke study. Univariate analyses were added by multiple regression analyses.
      RESULTS: As compared with the control group, patients with sCAD had an increased
      leucocyte count (9.2 +/- 3.2 vs. 7.9 +/- 2.2 * 109/l; p = 0.003), an increased
      thrombocyte count (252 +/- 52 vs. 229 +/- 64 * 109/l; p = 0.021), a shortened
      aPTT 28.0 +/- 3.5 vs. 29.9 +/- 3.6 s; p = 0.001) and decreased D-dimer values
      (0.44 +/- 0.29 vs. 0.76 +/- 0.73 mg/l; p = 0.002). However, in multiple
      regression analyses adjusted for age, sex, initial stroke severity, arterial
      hypertension, diabetes mellitus and smoking only the shortened aPTT remained
      statistically significant (p = 0.045) between groups, while differences on
      leucocyte count (p = 0.087), thrombocyte count (p = 0.234) and D-dimer (p =
      0.321) failed statistical significance. CONCLUSION: We found evidence for a
      hypercoagulable state in patients with sCAD as indicated by a shortened aPTT,
      which was associated with a trend to an increased leucocyte count at the same
      time. Our findings first strengthen the hypothesis that inflammation critically
      impacts on the occurrence of sCAD, and second linked this condition with a marked
      affection of the coagulation system.

PMID- 29224121
TI  - High-definition infrared thermography of ice nucleation and propagation in wheat
      under natural frost conditions and controlled freezing.
AB  - MAIN CONCLUSION: An extremely high resolution infrared camera demonstrated
      various freezing events in wheat under natural conditions. Many of those events
      shed light on years of misunderstanding regarding freezing in small grains.
      Infrared thermography has enhanced our knowledge of ice nucleation and
      propagation in plants through visualization of the freezing process. The majority
      of infrared analyses have been conducted under controlled conditions and often on
      individual organs instead of whole plants. In the present study, high-definition
      (1280 * 720 pixel resolution) infrared thermography was used under natural
      conditions to visualize the freezing process of wheat plants during freezing
      events in 2016 and 2017. Plants within plots were found to freeze one at a time
      throughout the night and in an apparently random manner. Leaves on each plant
      also froze one at a time in an age-dependent pattern with oldest leaves freezing
      first. Contrary to a common assumption that freezing begins in the upper parts of
      leaves; freezing began at the base of the plant and spread upwards. The high
      resolution camera used was able to verify that a two stage sequence of freezing
      began within vascular bundles. Neither of the two stages was lethal to leaves,
      but a third stage was demonstrated at colder temperatures that was lethal and was
      likely a result of dehydration stress; this stage of freezing was not detectable
      by infrared. These results underscore the complexity of the freezing process in
      small grains and indicate that comprehensive observational studies are essential
      to identifying and selecting freezing tolerance traits in grain crops.

PMID- 29224122
TI  - Overfeed the Bold, Starve the Cowardly: A Legend or Reality?
AB  - Although the negative effects of overconfidence are more likely to be mentioned
      in the literature, some researchers have argued that the benefits of
      overconfidence may outweigh its costs. We attempted to explore the positive
      effects of overconfidence in competitive situations. We had participants compete
      against fake opponents who were overconfident and then measured their competitive
      performance in two studies. In Study 1 we examined the effects of overconfidence
      on competitive performance in a competitive situation and the possible mechanism
      for this overconfidence. In Study 2 we investigated the characteristics of the
      performance in a competition after a mismatch between the level of confidence and
      the fake opponent's actual competence was revealed. Our results indicated that
      overconfident individuals tend to be perceived as more competent and more likely
      to benefit in the process of competition. Even after a mismatch between the level
      of confidence and the real competence was revealed, the overconfident individuals
      were not punished in that they made as much money as the less overconfident and
      still got higher competence ratings. Together those studies suggested that
      overconfidence has its advantages in competitive situations.

PMID- 29224124
TI  - Underestimated effects of sediments on enhanced startup performance of biofilm
      systems for polluted source water pretreatment.
AB  - In order to evaluate the enhancement mechanisms of enhanced startup performance
      in biofilm systems for polluted source water pretreatment, three lab-scale
      reactors with elastic stereo media (ESM) were operated under different enhanced
      sediment and hydraulic agitation conditions. It is interesting to found the
      previously underestimated or overlooked effects of sediment on the enhancement of
      pollutants removal performance and enrichment of functional bacteria in biofilm
      systems. The maximum NH4+-N removal rate of 0.35 mg L-1 h-1 in sediment enhanced
      condition was 2.19 times of that in control reactor. Sediment contributed to 42.0
      56.5% of NH4+-N removal and 15.4-41.2% of total nitrogen removal in different
      reactors under different operation conditions. The enhanced hydraulic agitation
      with sediment further improved the operation performance and accumulation of
      functional bacteria. Generally, Proteobacteria (48.9-52.1%), Bacteroidetes (18.9
      20.8%) and Actinobacteria (15.7-18.5%) were dominant in both sediment and ESM
      bioiflm at  phylum level. The potentially functional bacteria found in sediment
      and ESM biofilm samples with some functional bacteria mainly presented in
      sediment samples only (e.g., Genera Bacillus and Lactococcus of Firmicutes
      phylum) may commonly contribute to the removal of nitrogen and organics.

PMID- 29224123
TI  - Shear wave sonoelastography of skeletal muscle: basic principles, biomechanical
      concepts, clinical applications, and future perspectives.
AB  - Imaging plays an important role in the diagnosis and therapeutic response
      evaluation of muscular diseases. However, one important limitation is its
      incapacity to assess the in vivo biomechanical properties of the muscles. The
      emerging shear wave sonoelastography technique offers a quantifiable spatial
      representation of the viscoelastic characteristics of skeletal muscle.
      Elastography is a non-invasive tool used to analyze the physiologic and
      biomechanical properties of muscles in healthy and pathologic conditions.
      However, radiologists need to familiarize themselves with the muscular
      biomechanical concepts and technical challenges of shear wave elastography. This
      review introduces the basic principles of muscle shear wave elastography,
      analyzes the factors that can influence measurements and provides an overview of
      its potential clinical applications in the field of muscular diseases.

PMID- 29224126
TI  - Perception of Community on Attachment and Resilience According to Closing of
      Hospitals.
AB  - This study includes a comparison analysis of how community resilience and its
      influence factor of community attachment were changed before and after the
      closing of the hospital in the rural community. In order to analyze the influence
      factors of healthcare and medical vulnerability on community resilience, as well
      as the mean difference from before and after the closing of the hospital, this
      study conducted matching sample t test, hierarchical regression analysis,
      difference in differences (DID) analysis. The results indicate that community
      attachment consists of such factors as closeness, preference, affective bond, and
      identity, and they showed significance in confidence. It showed that resilience
      and community attachment are lower after closing than before closing. Moreover,
      as a result of DID analysis where the variation of community attachment affects
      community resilience, closeness together with closeness had an influence on the
      community resilience. It needs to expand public projects to improve the
      settlement environment of the basic local government, and in particular, it
      should consider various support measures to overcome vulnerabilities in the
      healthcare and medical sector.

PMID- 29224125
TI  - Substitution of soybean meal with fermented Jatropha kernel meal: effect on
      growth performance, body composition, and metabolic enzyme activity of Labeo
      rohita.
AB  - A 60-day feeding trial was conducted to evaluate the nutritional potential of
      fermented Jatropha kernel meal (FJKM) in the diets of rohu, Labeo rohita,
      fingerlings. Four iso-nitrogenous (336 g kg-1) and iso-energetic (20 MJ kg-1)
      diets containing 0, 100, 200, and 300 g kg-1 FJKM in replacement of 0, 33.3,
      66.7, and 100% soybean meal protein, respectively, were prepared and designated
      as control, T1, T2, and T3, respectively. A total of 180 acclimatized fish
      (average weight 6.05 +/- 0.04 g) were equally distributed into four experimental
      groups in triplicates, and were fed their respective diets to satiation twice
      daily at 10:00 h and 18:00 h. Higher percent weight gain (%WG); specific growth
      rate (SGR); protein efficiency ratio (PER); protease, aspartate amino transferase
      (AST), and alanine amino transferase (ALT) activities; and lower feed conversion
      ratio (FCR) were recorded in T2 and T3 groups compared to other groups. Whereas
      hepatosomatic index (HSI), intestinal somatic index (ISI), and amylase, lactate
      dehydrogenase (LDH), malate dehydrogenase (MDH), superoxide dismutase (SOD), and
      catalase activities among the various dietary groups did not vary significantly
      (P > 0.05). Whole body composition of fish analyzed at the end of the feeding
      trial exhibited significantly (P < 0.05) higher ether extract and lower crude
      protein in the control group compared to the FJKM-fed groups. These results
      indicated that rohu fingerlings can efficiently utilize FJKM without any
      detrimental effect on growth performance, nutrient utilization, and metabolic
      response.

PMID- 29224128
TI  - Identification of a new begomovirus infecting Duranta repens in Pakistan.
AB  - Ornamental perennial plants may serve as reservoirs for viruses that infect field
      crops. Duranta repens is an ornamental shrub that frequently exhibits leaf curl
      symptoms typical of begomoviral infection. Two begomoviruses or DNA-A components
      (isolates 57SA and 58SA) along with a DNA-B component (31SA) were identified in a
      symptomatic D. repens plant. Isolates 57SA and 58SA showed the highest nucleotide
      sequence identity of 90% and 92.2% to catharanthus yellow mosaic virus (CaYMV)
      and chilli leaf curl India virus (ChiLCINV), respectively, whereas 31SA shared
      the highest nucleotide sequence identity of 95.2% with the DNA-B component of
      tomato leaf curl New Delhi Virus (ToLCNDV). Isolate 57SA (showing < 91% highest
      nucleotide sequence identity) may thus be considered a member of a distinct
      species, and we propose the name "duranta leaf curl virus" (DLCV) for this virus.
      In addition, isolate 58SA (showing highest nucleotide sequence identity < 94%) is
      a newly identified strain of ChiLCINV for which the name "Duranta" strain is
      proposed. Further analysis showed that 57SA, 58SA and 31SA are recombinant, again
      highlighting the importance of recombination in begomovirus evolution. This is
      the first identification of DLCV. Also, a mixed infection with two viruses (or
      DNA-A components) and one DNA-B is reported.

PMID- 29224127
TI  - Defining and characterizing sustained remission in patients with rheumatoid
      arthritis.
AB  - The objective of this study is to characterize stability and clinical features of
      patients with rheumatoid arthritis (RA) in sustained remission. Combination
      therapy with methotrexate and tumor necrosis factor inhibitors (TNFi) has
      increased remission rates in RA but optimal regimens to maintain remission are
      unknown. We describe Study of Etanercept And Methotrexate in Combination or as
      Monotherapy in Subjects with Rheumatoid Arthritis (SEAM-RA) and data from a run
      in period of longitudinal observation. Patients in Simplified Disease Activity
      Index (SDAI) remission (score <= 3.3) receiving etanercept and methotrexate were
      screened and had to maintain remission over 3 run-in visits/24 weeks before
      randomization to combination therapy or withdrawal of etanercept or methotrexate.
      Baseline characteristics were examined for predictive factors for maintaining
      remission. As of November 2016, 141 patients have enrolled; of these, 64 have
      been randomized, 34 were ineligible after run-in, and 43 are in run-in period;
      70% have completed run-in. Enrolled and randomized patients, respectively, had
      mean (standard deviation [SD]) disease duration 11.0 (8.6) and 12.6 (9.7) years;
      mean (SD) duration of etanercept use 4.2 (3.8) and 4.9 (4.2) years; mean (SD)
      methotrexate dose 15.9 (4.8) and 15.5 (4.9) mg/week; and mean (SD) SDAI scores
      1.5 (0.9) and 1.4 (0.8). At enrollment, 73% and 63% were in Boolean remission
      based on 28 joints and 66/68 joints, respectively. No enrollment characteristic
      predicted successful completion of run-in. Two-thirds of patients considered to
      be in remission at enrollment sustained remission through 24 weeks. Baseline
      characteristics of enrolled patients and those who completed run-in were
      comparable.

PMID- 29224129
TI  - Rymovirus: a cautionary tale.
AB  - A recent proposal that the genus Rymovirus be assimilated into the genus
      Potyvirus is examined, discussed, and rejected. It illustrates the danger of
      using 'sequence identity' as a proxy for phylogenetic relatedness to distinguish
      closely related but distinct groups of viruses.

PMID- 29224130
TI  - Molecular epidemiology and characterization of bovine leukemia virus in domestic
      yaks (Bos grunniens) on the Qinghai-Tibet Plateau, China.
AB  - Bovine leukemia virus (BLV) is a member of the genus Deltaretrovirus of the
      family Retroviridae and cause a chronic lymphosarcoma, which is extensive in
      cattle. In yaks (Bos grunniens), the distribution, strains and genetic
      characteristics of BLV have rarely been studied. The aim of our study was to
      investigate BLV infections in domestic yaks and determine the genetic variability
      of BLV circulating in a region of the Qinghai Tibet Plateau, China. Blood samples
      were collected from 798 yaks, which were from different farms from Gansu, Qinghai
      and Sichuan provinces surrounding the Qinghai-Tibet Plateau. Nested PCR targeting
      BLV long terminal repeats was used to detect the BLV provirus. The highest
      prevalence of BLV infection was in Gansu province, where it was 18.93% (39/206)
      in white yaks from Tianzhu City and 19.14% (31/162) in black yaks from Gannan
      City. In Qinghai and Sichuan provinces, the prevalence of BLV in black yaks was
      14.83% (35/236) and 14.94% (29/194), respectively. The prevalence of BLV was not
      significantly different in yaks up to one year old than in older animals.
      Phylogenetic analysis was performed using 16 different env-gp51 (497-bp) gene
      sequences from the three provinces and 71 known BLV strains, which revealed that
      in both Gansu and Qinghai provinces, genotypes 6 and 10 of the BLV strains were
      at high levels, whereas only genotype 10 was prevalent in Sichuan Province.
      Phylogenetic analysis and sequence comparisons revealed 95.7-99.8% sequence
      identity among the full-length env genes of 16 strains, nearly full-length genome
      sequences of six BLV strains, and those of the known genotypes 6 and 10 of BLV.
      This study provides comprehensive information is regarding the widespread
      infection of domestic yaks with BLV on the Qinghai-Tibet Plateau of China, and
      shows that at least two BLV genotypes (genotypes 6 and 10) are circulating in
      this population.

PMID- 29224131
TI  - Characterization of tomato leaf curl purple vein virus, a new monopartite New
      World begomovirus infecting tomato in Northeast Brazil.
AB  - A new begomovirus species was identified from tomato plants with upward leaf
      curling and purple vein symptoms, which was first identified in the Piaui state
      of Northeast (NE) Brazil in 2014. Tomato leaf samples were collected in 2014 and
      2016, and PCR with degenerate primers revealed begomovirus infection. Rolling
      circle amplification and restriction enzyme digestion indicated a single genomic
      DNA of ~ 2.6 kb. Cloning and sequencing revealed a genome organization similar to
      DNA-A components of New World (NW) bipartite begomoviruses, with no DNA-B. The
      complete nucleotide sequence had the highest identity (80%) with the DNA-A of
      Macroptilium yellow spot virus (MacYSV), and phylogenetic analyses showed it is a
      NW begomovirus that clusters with MacYSV and Blainvillea yellow spot virus, also
      from NE Brazil. Tomato plants agroinoculated with a dimeric clone of this genomic
      DNA developed upward leaf curling and purple vein symptoms, indistinguishable
      from those observed in the field. Based on agroinoculation, this virus has a
      narrow host range, mainly within the family Solanaceae. Co-inoculation
      experiments with tomato severe rugose virus and tomato mottle leaf curl virus,
      the two predominant begomoviruses infecting tomato in Brazil, revealed a
      synergistic interaction among these begomoviruses. The name Tomato leaf curl
      purple vein virus (ToLCPVV) is proposed for this new begomovirus.

PMID- 29224132
TI  - Treatment of mild-to-moderate hypoglycemia in patients with type 1 diabetes
      treated with insulin pump therapy: are current recommendations effective?
AB  - AIMS: Mild-to-moderate hypoglycemia (blood glucose < 4.0 mmol/L) is recommended
      to be treated with 15 g of carbohydrates and to repeat the treatment if
      hypoglycemia persists after 15 min. This recommendation was established before
      intensive insulin therapy and based on studies using insulin with different
      pharmacokinetic profiles from actual insulin analogs showing that 15 g of glucose
      increases blood glucose by ~ 1.5 mmol/L in 15 min. We aimed to explore the effect
      of current recommended treatment of mild-to-moderate hypoglycemia in type 1
      diabetes (T1D) participants and factors associated with treatment effectiveness.
      METHODS: This is a secondary analysis from three observational inpatient studies
      with a standardized and supervised treatment (16 g carbohydrates) of hypoglycemia
      (< 3.3 mmol/L with symptoms or < 3.0 mmol/L without symptom) in participants (47
      adults-10 adolescents) with T1D using continuous subcutaneous insulin infusion
      ("insulin pumps"; CSII)). RESULTS: Twenty-seven participants presented a total of
      48 hypoglycemia episodes treated by a single intake of 16 g of carbohydrates.
      Time required for normoglycemia recovery was 19.5 +/- 12.0 min. The rise in
      plasma glucose following treatment was 0.85 +/- 0.66 mmol/L in 15 min. Eighteen
      episodes (38%) were resolved (> 4.0 mmol/L) 15-min post-treatment. Glycemia at
      the time of treatment (< 3.2 mmol/L; p < 0.001) and a higher proportion of total
      daily insulin from basal doses (p = 0.03) were associated with a slower post
      treatment plasma glucose rise. CONCLUSIONS: These results raise the possibility
      that sixteen grams of carbohydrates could be insufficient to treat a large
      proportion of hypoglycemia episodes in T1D patients treated with CSII. Factors
      affecting treatment effectiveness need to be investigated.

PMID- 29224133
TI  - Epidemiology of chronic hepatitis B virus in Ireland using routinely collected
      surveillance and administrative data, 2004-2014.
AB  - BACKGROUND: Ireland has a low prevalence of chronic hepatitis B virus (HBV)
      infection; however, there are limited recently published epidemiological data.
      This study aimed to describe the epidemiology of chronic HBV in Ireland between
      2004 and 2014 using routine surveillance data and identify and interrogate
      additional data sources in Ireland to complement the interpretation of HBV
      surveillance data. METHODS: Routinely collected passive surveillance data of
      notified cases of HBV infection were collated for 2004-2014. Additional data
      sources relating to primary liver cancer and cirrhosis were collated, including
      hospital discharge data (2005-2013), diagnoses of primary liver cancer (2004
      2013), and deaths (2007-2014). Publicly available immigration (2004-2014) data
      were also collated. RESULTS: Between 2004 and 2014, a total of 7463 notifications
      of HBV were made in Ireland; the majority (91%) were classified as chronic cases.
      Notifications peaked in 2008 and decreased until 2013. Hospital discharges, new
      cancer registrations, and deaths from primary liver cancer and hospital
      discharges from cirrhosis have increased each year. DISCUSSION: The epidemiology
      of HBV in Ireland mirrors immigration patterns. Without a coordinated screening
      and care programme for priority populations, particularly for immigrants from
      high prevalence countries, it is likely that hospitalisations and deaths from HBV
      attributable cirrhosis and primary liver cancer will continue to rise, with
      considerable associated public health expense.

PMID- 29224134
TI  - Tree-like colour Doppler in diagnosing pneumonia in critically ill: a picture is
      worth a thousand words.

PMID- 29224135
TI  - Serum ferritin and obstructive sleep apnea-epidemiological study.
AB  - PURPOSE: Ferritin is an intracellular iron storage protein and a marker of
      inflammation. Studies have shown that subjects with obstructive sleep apnea (OSA)
      have higher levels of circulating pro-inflammatory cytokines, but little is known
      about the association between ferritin and OSA. The aims of the study were to
      evaluate serum ferritin (S-Ferritin) levels in OSA patients compared to levels in
      the general population and also examine the effect of obesity level and treatment
      with positive airway pressure (PAP) on S-Ferritin levels. METHODS: The OSA
      subjects (n = 796) were part of the Icelandic Sleep Apnea Cohort. The control
      subjects (n = 637) were randomly chosen Icelanders who participated in an
      epidemiological study. Propensity score (PS) methodologies were employed to
      minimize selection bias and strengthen causal inferences when comparing non
      randomized groups. S-Ferritin levels were measured and all participants answered
      the same detailed questionnaire about sleep and health. Only OSA patients
      underwent a sleep study and were re-invited for a 2-year follow-up. RESULTS: S
      Ferritin levels were significantly higher in OSA males than controls (213.3 vs.
      197.3 MUg/L, p = 0.007). However, after adjusting for confounders and using our
      PS methodology, no significant difference was found. S-Ferritin levels were not
      correlated with severity of OSA, obesity level, or clinical symptoms. Also, no
      significant change in S-Ferritin levels was found with 2 years of PAP treatment.
      CONCLUSIONS: S-Ferritin levels are comparable in OSA patients and controls and do
      not change consistently with obesity level or PAP treatment in our sample.

PMID- 29224136
TI  - A Summary of the Biological Processes, Disease-Associated Changes, and Clinical
      Applications of DNA Methylation.
AB  - DNA methylation at cytosines followed by guanines, CpGs, forms one of the
      multiple layers of epigenetic mechanisms controlling and modulating gene
      expression through chromatin structure. It closely interacts with histone
      modifications and chromatin remodeling complexes to form the local genomic and
      higher-order chromatin landscape. DNA methylation is essential for proper
      mammalian development, crucial for imprinting and plays a role in maintaining
      genomic stability. DNA methylation patterns are susceptible to change in response
      to environmental stimuli such as diet or toxins, whereby the epigenome seems to
      be most vulnerable during early life. Changes of DNA methylation levels and
      patterns have been widely studied in several diseases, especially cancer, where
      interest has focused on biomarkers for early detection of cancer development,
      accurate diagnosis, and response to treatment, but have also been shown to occur
      in many other complex diseases. Recent advances in epigenome engineering
      technologies allow now for the large-scale assessment of the functional relevance
      of DNA methylation. As a stable nucleic acid-based modification that is
      technically easy to handle and which can be analyzed with great reproducibility
      and accuracy by different laboratories, DNA methylation is a promising biomarker
      for many applications.

PMID- 29224137
TI  - Considerations for Design and Analysis of DNA Methylation Studies.
AB  - The number of epigenetic studies is exponentially increasing. There is
      anticipation that DNA methylation may close gaps in our understanding of disease
      etiology, and how certain risk factors affect health and disease, but also that
      it has potential as a biomarker for disease. Human DNA methylation studies
      require careful considerations for design and analysis including population and
      tissue selection, population stratification, cell heterogeneity, confounding,
      temporality, sample size, appropriate statistical analysis, and validation of
      results. In this chapter, we discuss relevant aspects for the design of DNA
      methylation studies and delineate essential steps for their analysis.
      Specifically, we summarize methods used to extricate biologic signals from
      technical noise, and statistical approaches to capture meaningful variability
      based on the research hypothesis.

PMID- 29224138
TI  - Quantification of Global DNA Methylation Levels by Mass Spectrometry.
AB  - Global DNA methylation was classically considered the relative percentage of 5
      methylcysine (5mC) with respect to total cytosine (C). Early approaches were
      based on the use of high-performance separation technologies and UV detection.
      However, the recent development of protocols using mass spectrometry for the
      detection has increased sensibility and permitted the precise identification of
      peak compounds based on their molecular masses. This allows work to be conducted
      with much less genomic DNA starting material and also to quantify 5-hydroxymethyl
      cytosine (5hmC), a recently identified form of methylated cytosine that could
      play an important role in active DNA demethylation. Here, we describe the
      protocol that we currently use in our laboratory to analyze 5mC and 5hmC by mass
      spectrometry. The protocol, which is based on the method originally developed by
      Le and colleagues using Ultra Performance Liquid Chromatography (UPLC) and mass
      spectrometry (triple Quadrupole (QqQ)) detection, allows for the rapid and
      accurate quantification of relative global 5mC and 5hmC levels starting from just
      1 MUg of genomic DNA, which allows for the rapid and accurate quantification of
      relative global 5mC and 5hmC levels.

PMID- 29224139
TI  - Antibody-Based Detection of Global Nuclear DNA Methylation in Cells, Tissue
      Sections, and Mammalian Embryos.
AB  - Immunostaining is widely used in cell biology for the in situ detection of
      proteins in fixed cells. The method is based on the specificity of antibodies for
      recognizing and binding to a selected target, combined with immunolabeling
      techniques for microscopic imaging. Antibodies with high specificities for
      modified nucleotides have also been widely developed, and among those, antibodies
      that recognize modified cytosine: 5-methylcytosine (5mC), and more recently, its
      derivates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5
      carboxylcytosine (5caC). To allow for their detection, primary antibody signals
      can be amplified using secondary antibodies coupled to fluorophores for
      immunofluorescence, or other molecules for immunocytochemistry.Immunostaining can
      be used to gain information on the spatial distribution and levels of DNA
      methylation states within the nucleus. Although the resolution remains quite low
      in genomic terms, advanced microscopy techniques and image analysis can obtain
      detailed spatial information content from immunostained sites. The technique
      complements genomic approaches that permit the assessment of DNA methylation on
      specific sequences, but that cannot provide global nuclear spatial context.
      Immunostaining is an accessible method of great benefit in several cases: when
      working with limited material (such as embryos or primary cells), to quickly
      assess at the level of individual cells the effect of siRNA, drugs, or biological
      processes that promote or inhibit DNA methylation or demethylation, or to study
      the 3D nuclear organization of regions with high DNA methylation, such as
      constitutive heterochromatin.Here, we review and outline protocols for the
      fluorescent and enzymatic immunodetection of DNA methylation in the nuclei of
      cells, tissue sections, and mammalian embryos.

PMID- 29224140
TI  - Whole-Genome Bisulfite Sequencing Using the Ovation(r) Ultralow Methyl-Seq
      Protocol.
AB  - The analysis of genome-wide epigenomic alterations including DNA methylation has
      become a subject of intensive research for many complex diseases. Whole-genome
      bisulfite sequencing (WGBS) using next-generation sequencing technologies can be
      considered the gold standard for a comprehensive and quantitative analysis of
      cytosine methylation throughout the genome. Several approaches including
      tagmentation- and post bisulfite adaptor tagging (PBAT)-based WGBS have been
      devised. Here, we provide a detailed protocol based on a commercial kit for the
      preparation of libraries for WGBS from limited amounts of input DNA (50-100 ng)
      using the classical approach of WGBS by ligation of methylated adaptors to the
      fragmented DNA prior to bisulfite conversion. The converted library is then
      amplified with an optimal number of PCR cycles to ensure high sequence diversity
      and low duplicate rates. Spike-in of unmethylated DNA allows for the precise
      estimation of bisulfite conversion rates. We also provide a step-by-step
      description of the data analysis using publicly available bioinformatic tools.
      The described protocol has been successfully applied to different human samples
      as well as DNA extracted from plant tissues and yields robust and reproducible
      results.

PMID- 29224141
TI  - Tagmentation-Based Library Preparation for Low DNA Input Whole Genome Bisulfite
      Sequencing.
AB  - Aberrations of the DNA methylome contribute to onset and progression of diseases.
      Whole genome bisulfite sequencing (WGBS) is the only analytical method covering
      the complete methylome. Alternative methods requiring less DNA than WGBS analyze
      only a minor portion of the methylome and do not cover important regulatory
      features like enhancers and noncoding RNAs. In tagmentation-based WGBS (TWGBS),
      several DNA and time-consuming steps of the conventional WGBS library preparation
      are circumvented by the use of a hyperactive transposase, which simultaneously
      fragments DNA and appends sequencing adapters. TWGBS requires only nanogram
      amounts of DNA and, thus, is well suited to study precious biological specimens
      such as sorted cells or micro-dissected tissue samples.

PMID- 29224142
TI  - Post-Bisulfite Adaptor Tagging for PCR-Free Whole-Genome Bisulfite Sequencing.
AB  - Post-bisulfite adaptor tagging (PBAT) is a highly efficient procedure to
      construct libraries for whole-genome bisulfite sequencing (WGBS). PBAT attaches
      adaptors to bisulfite-converted genomic DNA to circumvent bisulfite-induced
      degradation of library DNA inherent to conventional WGBS protocols. Consequently,
      it enables PCR-free WGBS from nanogram quantities of mammalian DNA, thereby
      serving as an invaluable tool for methylomics.

PMID- 29224143
TI  - Multiplexed Reduced Representation Bisulfite Sequencing with Magnetic Bead
      Fragment Size Selection.
AB  - Reduced representation bisulfite sequencing (RRBS) is a technique for assessing
      genome-wide DNA methylation in an organism whose genome has been fully sequenced.
      It allows researchers to target gene regions with particular CpG densities,
      thereby selecting the desired genomic contexts. Here, we describe an approach
      that uses magnetic beads to accomplish this selection. In addition, the use of
      indexed, methylated adapters enables up to 12 samples to be pooled, and subjected
      to multiplexed RRBS in a single-sequencing lane. First, genomic DNA is fragmented
      via restriction endonuclease digestion that ensures at least two CpG loci per
      fragment. The fragmented DNA is then end-repaired and A-tailed. Indexed,
      methylated adapters are ligated to the A-tailed DNA fragments to create a DNA
      library. A combination of negative and positive selections, using magnetic beads
      that preferentially bind to larger DNA fragments, ensures that only the desired
      sizes of adapter-ligated DNA fragments are included in a library. This allows
      researchers to dictate what types of genomic regions will be sequenced, since
      fragment size depends on the proximity of restriction sites. The DNA libraries
      are then quantified, and up to 12 libraries are pooled in order to be sequenced
      on a single lane of an Illumina HiSeq2500. The pools are next treated with sodium
      bisulfite, and then PCR amplified. A final bead cleanup removes any residual
      contaminants prior to sequencing, which is followed by base calling and alignment
      to a sequenced genome.

PMID- 29224144
TI  - Low Input Whole-Genome Bisulfite Sequencing Using a Post-Bisulfite Adapter
      Tagging Approach.
AB  - The epigenetic mark 5-methylcytosine confers heritable regulation of gene
      expression that can be dynamically modulated during transitions in cell fate.
      With the development of high-throughput sequencing technologies, it is now
      possible to obtain comprehensive genome-wide maps of the mammalian DNA
      methylation landscape, but the application of these techniques to limited
      material remains challenging. Here, we present an optimized protocol to perform
      whole-genome bisulfite sequencing on low inputs (100-5000 somatic cells) using a
      post-bisulfite adapter tagging approach. In this strategy, bisulfite treatment is
      performed prior to library generation in order to both convert unmethylated
      cytosines and fragment DNA to an appropriate size. Then sequencing adapters are
      added by complementary strand synthesis using random tetramer priming, and
      libraries are subsequently amplified by PCR.

PMID- 29224145
TI  - Methyl-CpG-Binding Domain Sequencing: MBD-seq.
AB  - Detailed biological knowledge about the potential importance of the methylome is
      typically lacking for common diseases. Therefore, methylome-wide association
      studies (MWAS) are critical to detect disease relevant methylation sites. Methyl
      CpG-binding domain sequencing (MBD-seq) offers potential advantages compared to
      antibody-based enrichment, but performance depends critically on using an optimal
      protocol. Using an optimized protocol, MBD-seq can approximate the
      sensitivity/specificity obtained with whole-genome bisulfite sequencing, but at a
      fraction of the costs and time to complete the project. Thus, MBD-seq offers a
      comprehensive first pass at the CpG methylome and is economically feasible with
      the samples sizes required for MWAS.

PMID- 29224146
TI  - The HELP-Based DNA Methylation Assays.
AB  - Restriction enzymes have been valuable tools for representing the genome for DNA
      methylation assays, whether by using methylation-dependent enzymes or by sampling
      a reduced representation of the genome using a methylation-insensitive enzyme.
      These survey assays have remained mainstays of genome-wide approaches even with
      the development of more comprehensive shotgun genome-wide bisulphite sequencing
      based assays, as they are significantly more affordable. DNA methylation survey
      assays are numerous and include reduced representation bisulphite sequencing
      (RRBS), the Illumina HumanMethylation450K and EPIC microarray system, and our
      evolving series of HELP-based assays. The HELP (HpaII tiny fragment Enrichment by
      Ligation-mediated PCR) assays initially involved microarray-based reporting of
      DNA methylation, but have now migrated to the use of massively parallel
      sequencing. In this chapter, we describe the latest HELP-tagging assay that uses
      Illumina Tru-Seq adapters, and mention the extension of the HELP-tagging assay to
      quantify 5-hydroxymethylation using the HELP-GT assay.

PMID- 29224148
TI  - Digital Restriction Enzyme Analysis of Methylation (DREAM).
AB  - Digital Restriction Enzyme Analysis of Methylation (DREAM) is a method for
      quantitative mapping of DNA methylation across genomes using next-generation
      sequencing (NGS) technology. The method is based on sequential cuts of genomic
      DNA with a pair of restriction enzymes (SmaI and XmaI) at CCCGGG target sites.
      Unmethylated sites are first digested with SmaI. This enzyme cuts the sites in
      the middle at CCC^GGG, leaving behind blunt ended fragments. CpG methylation
      completely blocks SmaI; therefore, only unmethylated sites are cleaved. The
      remaining methylated sites are digested with XmaI in the next step. This enzyme
      is not blocked by CpG methylation. It cuts the recognition site sideways at
      C^CCGGG forming 5'-CCGG overhangs. The sequential cuts thus create distinct
      methylation-specific signatures at the ends of restriction fragments: 5'-GGG for
      unmethylated CpG sites and 5'-CCGGG for methylated sites. The DNA fragments
      resulting from the digestions are ligated to NGS adapters. Sequencing libraries
      are prepared using hexanucleotide barcodes for sample identification. Individual
      libraries with distinct barcodes are pooled and sequenced using a paired ends
      protocol. The sequencing reads are aligned to the genome and mapped to unique
      CCCGGG target sites. Methylation at individual CpG sites is calculated as the
      ratio of sequencing reads with the methylated signature to the total number of
      reads mapping to the site. Sequencing of 25 million reads per sample typically
      yields 50,000 unique CpG sites covered with hundreds of reads enabling accurate
      determination of DNA methylation levels. DREAM does not require bisulfite
      conversion, has a very low background, and has high sensitivity to low levels of
      methylation. The method is simple, cost-effective, quantitative, highly
      reproducible, and can be applied to any species.

PMID- 29224147
TI  - Comprehensive Whole DNA Methylome Analysis by Integrating MeDIP-seq and MRE-seq.
AB  - Understanding the role of DNA methylation often requires accurate assessment and
      comparison of these modifications in a genome-wide fashion. Sequencing-based DNA
      methylation profiling provides an unprecedented opportunity to map and compare
      complete DNA CpG methylomes. These include whole genome bisulfite sequencing
      (WGBS), Reduced-Representation Bisulfite-Sequencing (RRBS), and enrichment-based
      methods such as MeDIP-seq, MBD-seq, and MRE-seq. An investigator needs a method
      that is flexible with the quantity of input DNA, provides the appropriate balance
      among genomic CpG coverage, resolution, quantitative accuracy, and cost, and
      comes with robust bioinformatics software for analyzing the data. In this
      chapter, we describe four protocols that combine state-of-the-art experimental
      strategies with state-of-the-art computational algorithms to achieve this goal.
      We first introduce two experimental methods that are complementary to each other.
      MeDIP-seq, or methylation-dependent immunoprecipitation followed by sequencing,
      uses an anti-methylcytidine antibody to enrich for methylated DNA fragments, and
      uses massively parallel sequencing to reveal identity of enriched DNA. MRE-seq,
      or methylation-sensitive restriction enzyme digestion followed by sequencing,
      relies on a collection of restriction enzymes that recognize CpG containing
      sequence motifs, but only cut when the CpG is unmethylated. Digested DNA
      fragments enrich for unmethylated CpGs at their ends, and these CpGs are revealed
      by massively parallel sequencing. The two computational methods both implement
      advanced statistical algorithms that integrate MeDIP-seq and MRE-seq data. M&M is
      a statistical framework to detect differentially methylated regions between two
      samples. methylCRF is a machine learning framework that predicts CpG methylation
      levels at single CpG resolution, thus raising the resolution and coverage of
      MeDIP-seq and MRE-seq to a comparable level of WGBS, but only incurring a cost of
      less than 5% of WGBS. Together these methods form an effective, robust, and
      affordable platform for the investigation of genome-wide DNA methylation.

PMID- 29224149
TI  - Nucleosome Occupancy and Methylome Sequencing (NOMe-seq).
AB  - Various methodologies are available to interrogate specific components of
      epigenetic mechanisms such as DNA methylation or nucleosome occupancy at both the
      locus-specific and the genome-wide level. It has become increasingly clear,
      however, that comprehension of the functional interactions between epigenetic
      mechanisms is critical for understanding how cellular transcription programs are
      regulated or deregulated during normal and disease development. The Nucleosome
      Occupancy and Methylome sequencing (NOMe-seq) assay allows us to directly measure
      the relationship between DNA methylation and nucleosome occupancy by taking
      advantage of the methyltransferase M.CviPI, which methylates unprotected GpC
      dinucleotides to create a footprint of chromatin accessibility. This assay
      generates dual nucleosome occupancy and DNA methylation information at a single
      DNA molecule resolution using as little as 200,000 cells and in as short as 15
      min reaction time. DNA methylation levels and nucleosome occupancy status of
      genomic regions of interest can be subsequently interrogated by cloning PCR
      amplified bisulfite DNA and sequencing individual clones. Alternatively, NOMe-seq
      can be combined with next-generation sequencing in order to generate an
      integrated global map of DNA methylation and nucleosome occupancy, which allows
      for comprehensive examination as to how these epigenetic components correlate
      with each other.

PMID- 29224150
TI  - Bisulphite Sequencing of Chromatin Immunoprecipitated DNA (BisChIP-seq).
AB  - Epigenetic regulation plays a critical role in gene expression, cellular
      differentiation, and disease. There is a complex interplay between the different
      layers of epigenetic information, including DNA methylation, nucleosome
      positions, histone modifications, histone variants, and other important
      epigenetic regulators. The different modifications do not act independently of
      each other and their relationship plays an important role in governing the
      regulation of the epigenome. Of these, DNA methylation is the best-studied
      epigenetic modification in mammals. However, the direct relationship between DNA
      methylation and chromatin modifications has been difficult to unravel with
      existing technologies, with epigenome-wide integration studies still based on
      "overlaying" independent chromatin modification and DNA methylation maps.
      Bisulphite sequencing enables the methylation state of every cytosine residue to
      be analyzed across a given molecule in a strand-specific context. Here, we
      describe a direct approach to interrogating the DNA methylation status of
      specific chromatin-marked DNA, using high-throughput sequencing of bisulphite
      treated chromatin immunoprecipitated DNA (BisChIP-seq). This combined approach
      enables the exquisite relationship between chromatin-modified DNA or
      transcription factor-associated DNA and the methylation state of each targeted
      allele to be directly interrogated. BisChIP-Seq can now be widely applied genome
      wide to further understand the molecular relationship between DNA methylation and
      other important epigenetic regulators.

PMID- 29224151
TI  - A Guide to Illumina BeadChip Data Analysis.
AB  - The Illumina Infinium BeadChips are a powerful array-based platform for genome
      wide DNA methylation profiling at approximately 485,000 (450K) and 850,000 (EPIC)
      CpG sites across the genome. The platform is used in many large-scale population
      based epigenetic studies of complex diseases, environmental exposures, or other
      experimental conditions. This chapter provides an overview of the key steps in
      analyzing Illumina BeadChip data. We describe key preprocessing steps including
      data extraction and quality control as well as normalization strategies. We
      further present principles and guidelines for conducting association analysis at
      the individual CpG level as well as more sophisticated pathway-based association
      tests.

PMID- 29224152
TI  - Microdroplet PCR for Highly Multiplexed Targeted Bisulfite Sequencing.
AB  - Many methods exist for examining CpG DNA methylation. However, many of these are
      qualitative, laborious to apply to a large number of genes simultaneously, or are
      not easy to target to specific regions of interest. Microdroplet PCR-based
      bisulfite sequencing allows for quantitative single base resolution analysis of
      investigator selected regions of interest. Following bisulfite conversion of
      genomic DNA, targeted microdroplet PCR is conducted with custom primer libraries.
      Samples are then fragmented, concatenated, and sequenced by high-throughput
      sequencing. The most recent technology allows for this method to be conducted
      with as little as 250 ng of bisulfite-converted DNA. The primary advantage of
      this method is the ability to hand-select the targeted regions covered by up to
      10,000 amplicons of 500-600 bp. Moreover, the nature of microdroplet PCR
      virtually eliminates PCR bias and allows for the amplification of all targets
      simultaneously in a single tube.

PMID- 29224153
TI  - Multiplexed DNA Methylation Analysis of Target Regions Using Microfluidics
      (Fluidigm).
AB  - Whole genome shotgun bisulfite sequencing is a method used to generate genome
      wide methylation profiles. There are many available protocols to validate the
      results of this genome-wide method, but they mostly share the limitation of
      measuring methylation at a small number of CpG positions in small numbers of
      samples. We developed a multiplexed DNA methylation analysis protocol, which
      allows for the simultaneous quantitative measurement of cytosine methylation at
      single nucleotide resolution in 48 PCR amplicons and 48 samples utilizing the
      microfluidic system established by Fluidigm. Following bisulfite conversion of
      500 ng of the target DNA, a PCR reaction is performed using a 48.48 Access Array,
      which allows parallel amplification of 48 samples by 48 primer pairs. The
      products of each reaction are labeled with individual, sample specific tags,
      pooled in a single library and sequenced using the Illumina MiSeq sequencer. The
      advantages of this system are: speed, small amount of input material, single
      nucleotide resolution, high coverage of each locus, low cost of simultaneously
      assaying multiple CpG loci in multiple DNA samples and high reproducibility.

PMID- 29224154
TI  - Large-Scale Targeted DNA Methylation Analysis Using Bisulfite Padlock Probes.
AB  - Bisulfite padlock probes (BSPP) are a method for the targeted quantification of
      DNA methylation in mammalian genomes. They can simultaneously characterize the
      level of methylcytosine modification in a large number of targeted regions at
      single-base resolution. A major advantage of BSPP is that it allows the flexible
      capture of an arbitrary subset of genomic regions (hundreds to hundreds of
      thousands of genomic loci) in single-tube reactions. Large number of samples can
      be processed efficiently and converted into multiplexed sequencing libraries with
      only three enzymatic steps, without the conventional library preparation
      procedures. BSPP are applicable to clinical studies, screening cell lines, and
      for quantifying low abundance regions using deep sequencing.

PMID- 29224155
TI  - Targeted Bisulfite Sequencing Using the SeqCap Epi Enrichment System.
AB  - Cytosine methylation has been shown to have a role in a host of biological
      processes. In mammalian biology these include stem cell differentiation,
      embryonic development, genomic imprinting, inflammation, and silencing of
      transposable elements. Given the central importance of these processes, it is not
      surprising to find aberrant cytosine methylation patterns associated with many
      disorders in humans, including cancer, cardiovascular disease, and neurological
      disease. While whole genome shotgun bisulfite sequencing (WGBS) has recently
      become feasible, generating high sequence coverage data for the entire genome is
      expensive, both in terms of money and analysis time, when generally only a small
      subset of the genome is of interest to most researchers. This report details a
      procedure for the targeted enrichment of bisulfite treated DNA via SeqCap Epi,
      allowing high resolution focus of next generation sequencing onto a subset of the
      genome for high resolution cytosine methylation analysis. Regions ranging in size
      from only a few kb up to over 200 Mb may be targeted, including the use of the
      SeqCap Epi CpGiant design which is designed to target 5.5 million CpGs in the
      human genome. Finally, multiple samples may be multiplexed and sequenced together
      to provide an inexpensive method of generating methylation data for a large
      number of samples in a high throughput fashion.

PMID- 29224156
TI  - Multiplexed and Sensitive DNA Methylation Testing Using Methylation-Sensitive
      Restriction Enzymes "MSRE-qPCR".
AB  - DNA methylation is a chemically stable key-player in epigenetics. In the
      vertebrate genome the 5-methyl cytosine (5mC) has been found almost exclusively
      in the CpG dinucleotide context. CpG dinucleotides are enriched in CpG islands
      very frequently located within or close to gene promoters. Analyses of DNA
      methylation changes in human diagnostics have been conducted classically using
      methylation-sensitive restriction enzymes (MSRE). Since the discovery of
      bisulfite conversion-based sequencing and PCR assays, MSRE-based PCR assays have
      been less frequently used, although especially in the field of cancer epigenetics
      MSRE-based genome-wide discovery and targeted screening applications have been
      and are still performed successfully. Even though epigenome-wide discovery of
      altered DNA methylation patterns has found its way into various fields of human
      disease and molecular genetics research, the validation of findings upon
      discovery is still a bottleneck. Usually several multiples of 10 up to 100
      candidate biomarkers from discovery have to be confirmed or are of interest for
      further work. In particular, bisulfite PCR assays are often limited in the number
      of candidates which can be analyzed, due to their low multiplexing capability,
      especially, if only small amounts of DNA are available from for example clinical
      specimens. In clinical research and diagnostics a similar situation arises for
      the analyses of cell-free DNA (cfDNA) in body fluids or circulating tumor cells
      (CTCs). Although tissue- or disease- (e.g., cancer) specific DNA methylation
      patterns can be deduced very efficiently in a genome-wide manner if around 100 ng
      of DNA are available, confirming these candidates and selecting target-sequences
      for studying methylation changes in liquid biopsies using cfDNA or CTCs remains a
      big challenge. Along these lines we have developed MSRE-qPCR and introduce here
      method details, which have been found very suitable for the efficient
      confirmation and testing of DNA methylation in a quantitative multiplexed manner
      (e.g., 48-96 plex) from ng amounts of DNA. The method is applicable in a standard
      qPCR setting as well for nanoliter scaled high-throughput qPCR, enabling
      detection of <10 copies of targets, thus suitable to pick up 0.1-1% of specific
      methylated DNA in an unmethylated background.

PMID- 29224158
TI  - Methylation-Specific PCR.
AB  - Cytosine methylation is a DNA modification generally associated with
      transcriptional silencing. Factors that regulate methylation have been linked to
      human disease, yet how they contribute to malignancies remains largely unknown.
      Methylation of DNA can change the functional state of regulatory regions, but
      does not change the Watson-Crick base pairing of cytosine. Moreover, sequence
      symmetry of CpGs enables propagation of the methyl mark through cell division.
      This potential for inheritance coupled with the fact that DNA methylation
      patterns change during development and disease partially explains the interest in
      DNA methylation as a memory module. DNA methylation analysis also provides an
      opportunity to discover new and more powerful biomarkers that can help in
      clinical practice.Methylation-Specific PCR (MSP) is likely the most widely used
      technique to study DNA methylation of a locus of interest. MSP can rapidly detect
      the methylation status of any group of CpG sites within a CpG island, not
      requiring methylation-sensitive restriction enzymes. It also requires minute
      amounts of DNA, is very sensitive as it can detect <0.1% of methylated alleles in
      a specific locus, and can be used in different samples, including bodily fluids,
      and paraffin-embedded samples.

PMID- 29224157
TI  - Quantitative DNA Methylation Analysis at Single-Nucleotide Resolution by
      Pyrosequencing(r).
AB  - Many protocols for gene-specific DNA methylation analysis are either labor
      intensive, not quantitative and/or limited to the measurement of the methylation
      status of only one or very few CpG positions. Pyrosequencing is a real-time
      sequencing technology that overcomes these limitations. After bisulfite
      modification of genomic DNA, a region of interest is amplified by PCR with one of
      the two primers being biotinylated. The PCR generated template is rendered single
      stranded and a pyrosequencing primer is annealed to analyze quantitatively
      cytosine methylation. In comparative studies, pyrosequencing has been shown to be
      among the most accurate and reproducible technologies for locus-specific DNA
      methylation analyses and has become a widely used tool for the validation of DNA
      methylation changes identified in genome-wide studies as well as for locus
      specific analyses with clinical impact such as methylation analysis of the MGMT
      promoter. Advantages of the Pyrosequencing technology are the ease of its
      implementation, the high quality and the quantitative nature of the results, and
      its ability to identify differentially methylated positions in close proximity.

PMID- 29224159
TI  - Quantitation of DNA Methylation by Quantitative Multiplex Methylation-Specific
      PCR (QM-MSP) Assay.
AB  - The defining feature of the Quantitative Multiplex Methylation-Specific PCR (QM
      MSP) method to sensitively quantify DNA methylation is the two-step PCR approach
      for a multiplexed analysis of a panel of up to 12 genes in clinical samples with
      minimal quantities of DNA. In the first step, for up to 12 genes tested, one pair
      of gene-specific primers (forward and reverse) amplifies the methylated and
      unmethylated copies of the same gene simultaneously and in multiplex, in one PCR
      reaction. This methylation-independent amplification step produces amplicons of
      up to 109 copies per MUL after 36 cycles of PCR. In the second step, the
      amplicons of the first reaction (STEP 1) are quantified with a standard curve
      using real-time PCR and two independent fluorophores to detect
      methylated/unmethylated DNA of each gene in the same well (e.g., 6FAM and VIC).
      One methylated copy is detectable in 100,000 reference gene copies. Methylation
      is reported on a continuous scale. For the gene panel, the highest level of
      normal DNA methylation above which a sample would be called positive is derived
      by using Receiver Operating Characteristic (ROC), maximizing assay specificity
      and sensitivity to distinguish between normal/benign versus tumor DNA. QM-MSP can
      be applied to clinical samples of fresh or fixed ductal cells, ductal fluid,
      nipple fluid, fine needle aspirates, core biopsies, and tumor tissue sections.

PMID- 29224160
TI  - MethyLight and Digital MethyLight.
AB  - MethyLight is a quantitative, fluorescence-based, real-time PCR method to
      sensitively detect and quantify DNA methylation of candidate regions of the
      genome. MethyLight is uniquely suited for detecting low-frequency methylated DNA
      regions against a high background of unmethylated DNA, as it combines methylation
      specific priming with methylation-specific fluorescent probing. The quantitative
      accuracy of real-time PCR and the ability to design bisulfite-dependent, DNA
      methylation-independent control reactions together allow for a quantitative
      assessment of these low frequency methylation events. Here we describe the
      experimental steps of MethyLight analysis in detail. Furthermore, we present
      principles and design examples for three types of quality control reactions. QC-1
      reactions are methylation-independent reactions to monitor sample quantity and
      integrity. QC-2 reactions are bisulfite-independent reactions to monitor recovery
      efficiencies of the bisulfite conversion methodology used. QC-3 reactions are
      bisulfite-independently primed reactions with variable bisulfite-dependent
      probing to monitor completeness of the sodium bisulfite treatment. We show that
      these control reactions perform as expected in a time course experiment
      interrupting sodium bisulfite conversion at various timepoints. Finally, we
      describe Digital MethyLight, in which MethyLight is combined with Digital PCR,
      for the highly sensitive detection of individual methylated molecules, with use
      in disease detection and screening.

PMID- 29224161
TI  - Quantitative Region-Specific DNA Methylation Analysis by the EpiTYPERTM
      Technology.
AB  - DNA methylation plays a profound role in development and health as well as
      development and progression of disease. High-throughput quantitative DNA
      methylation analysis is therefore crucial for the study of the normal physiology
      of the epigenome and its dysregulation in disease. Many target areas are
      identified by a range of emerging genome-wide cytosine methylation techniques,
      but these whole genome scans usually only provide methylation data for a few
      individual CpG sites (CpGs) within a region. The EpiTYPERTM assay is a region
      specific method for the detection and quantitative analysis of DNA methylation
      that allows performing a high-resolution scan of selected regions. It thus
      enables a more detailed analysis of single CpGs and the surrounding area and can,
      in addition to candidate gene methylation analysis, be used to validate CpGs
      detected by genome wide techniques. The EpiTYPERTM assay allows a fast and
      reproducible targeted quantification of individual CpGs in a high throughput
      manner and is based on base-specific cleavage of bisulfite-converted genomic DNA
      and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS). Up to 85% of the CpGs within a target region can be analyzed and
      the detection precision allows quantifying methylation differences as low as 5
      7%.

PMID- 29224162
TI  - Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA).
AB  - This chapter describes a method for the rapid assessment of promoter
      hypermethylation levels or methylation of imprinted regions in human genomic DNA
      extracted from various sources using methylation-specific multiplex ligation
      dependent probe amplification (MS-MLPA). Multiplex ligation-dependent probe
      amplification (MLPA) is a powerful and easy-to-perform PCR-based technique that
      can identify gains, amplifications, losses, deletions, methylation and mutations
      of up to 55 targets in a single reaction, while requiring only minute quantities
      of DNA (about 50 ng) extracted from blood, fresh frozen or formalin-fixed
      paraffin-embedded materials. Methylation-specific MLPA (MS-MLPA) is a variant of
      MLPA, which does not require sodium bisulfite conversion of unmethylated cytosine
      residues, but instead makes use of the methylation-sensitive endonuclease HhaI.
      MS-MLPA probes are designed to contain a HhaI recognition site (GCGC) and thus
      target one CpG dinucleotide within a CpG island. If the HhaI recognition site is
      not methylated, HhaI will cut the probe-sample DNA hybrid and no PCR product will
      be formed. If the target DNA is methylated, HhaI is not able to cut, and the
      fragment will be amplified during subsequent PCR. For data analysis, MS-MLPA peak
      patterns of the HhaI-treated and -untreated reactions are compared, leading to
      calculation of a methylation percentage. The methylation profile of a test sample
      is assessed by comparing the probe methylation percentages obtained on the test
      sample to the percentages of the reference samples. MS-MLPA can be combined with
      copy number and point mutation detection in the same reaction.

PMID- 29224163
TI  - Methylation-Sensitive High Resolution Melting (MS-HRM).
AB  - Methylation-Sensitive High Resolution Melting (MS-HRM) is an in-tube, PCR-based
      method to detect methylation levels at specific loci of interest. A unique primer
      design facilitates a high sensitivity of the assays enabling detection of down to
      0.1-1% methylated alleles in an unmethylated background.Primers for MS-HRM assays
      are designed to be complementary to the methylated allele, and a specific
      annealing temperature enables these primers to anneal both to the methylated and
      the unmethylated alleles thereby increasing the sensitivity of the assays.
      Bisulfite treatment of the DNA prior to performing MS-HRM ensures a different
      base composition between methylated and unmethylated DNA, which is used to
      separate the resulting amplicons by high resolution melting.The high sensitivity
      of MS-HRM has proven useful for detecting cancer biomarkers in a noninvasive
      manner in urine from bladder cancer patients, in stool from colorectal cancer
      patients, and in buccal mucosa from breast cancer patients. MS-HRM is a fast
      method to diagnose imprinted diseases and to clinically validate results from
      whole-epigenome studies. The ability to detect few copies of methylated DNA makes
      MS-HRM a key player in the quest for establishing links between environmental
      exposure, epigenetic changes, and disease.

PMID- 29224164
TI  - Hairpin Bisulfite Sequencing: Synchronous Methylation Analysis on Complementary
      DNA Strands of Individual Chromosomes.
AB  - The accurate and quantitative detection of 5-methylcytosine is of great
      importance in the field of epigenetics. The method of choice is usually bisulfite
      sequencing because of the high resolution and the possibility to combine it with
      next generation sequencing. Nevertheless, also this method has its limitations.
      Following the bisulfite treatment DNA strands are no longer complementary such
      that in a subsequent PCR amplification the DNA methylation patterns information
      of only one of the two DNA strand is preserved. Several years ago Hairpin
      Bisulfite sequencing was developed as a method to obtain the pattern information
      on complementary DNA strands. The method requires fragmentation (usually by
      enzymatic cleavage) of genomic DNA followed by a covalent linking of both DNA
      strands through ligation of a short DNA hairpin oligonucleotide to both strands.
      The ligated covalently linked dsDNA products are then subjected to a conventional
      bisulfite treatment during which all unmodified cytosines are converted to
      uracils. During the treatment the DNA is denatured forming noncomplementary ssDNA
      circles. These circles serve as a template for a locus specific PCR to amplify
      chromosomal patterns of the region of interest. As a result one ends up with a
      linearized product, which contains the methylation information of both
      complementary DNA strands.

PMID- 29224165
TI  - Helper-Dependent Chain Reaction (HDCR) for Selective Amplification of Methylated
      DNA Sequences.
AB  - Over the last few years a number of restriction enzymes that cut DNA only if
      cytosines within their recognition sequences are methylated have been
      characterized and become commercially available. Cleavage with these enzymes to
      release DNA fragments in a methylation-dependent manner can be combined with a
      novel method of amplification, Helper Dependent Chain Reaction (HDCR), to
      selectively amplify these fragments. HDCR uses "Helper" oligonucleotides as
      templates for extension of the free 3' end of target fragments to incorporate tag
      sequences at the ends of fragments. These tag sequences are then used for priming
      of amplification of target fragments. Modifications to the amplification primers
      (Drivers) and the Helpers ensure that there is selection for the sequences within
      target fragments with each cycle of amplification. The combination of methylation
      dependent enzymes and HDCR allows the sensitive and selective amplification of
      methylated DNA sequences without the need for bisulfite treatment.

PMID- 29224166
TI  - DNA Methylation Analysis from Blood Spots: Increasing Yield and Quality for
      Genome-Wide and Locus-Specific Methylation Analysis.
AB  - Blood represents an easily accessible human tissue for numerous research and
      clinical applications, including surrogate roles for biomarkers of other tissues.
      Dried blood spots (DBS) are space- and cost-efficient storage forms of blood
      while stably retaining many of its chemical constituents. Consequently, neonatal
      DBS are routinely collected in many countries, and their biobanks represent gold
      mines for research. However, the utility of DBS is restricted by the limited
      amount and quality of extractable biomolecules (including DNA), especially for
      genome-wide profiling. In particular, DNA methylome analysis in DBS has proven to
      be technically challenging, mainly due to the requirement for stringent
      preprocessing, such as bisulfite conversion. Moreover, DNA amplification,
      required to increase its yield, often leads to a bias in the analysis,
      particularly in methylome profiles. Thus, it is important to develop
      methodologies that maximize both the yield and quality of DNA from DBS for
      downstream analyses. Using a combination of in-house-derived and modified
      commercial extraction methods, we developed two robust protocols that produced
      increased DNA yield and quality from DBS. Though both protocols are more
      efficient relative to other published methods, one protocol yields less DNA
      compared to the other, but shows improved 260/280 spectrophotometric ratios,
      which are useful for sample quality assessment. Both protocols consist of two
      sequential phases, each involving several critical steps. Phase I comprises blood
      extraction off the filter papers, cell lysis, and protein digestion. Phase II
      involves DNA precipitation, purification, and elution. Results from subsequent
      locus-specific and genome-wide DNA methylation analyses demonstrate the high
      quality, reproducibility, and consistency of the data. This work may prove useful
      to meet the increased demand for research on DBS, particularly with a focus on
      the epigenetic origins of human diseases and newborn screening programs.

PMID- 29224167
TI  - DNA Methylation Analysis of Free-Circulating DNA in Body Fluids.
AB  - Circulating cell-free DNA in body fluids is an analyte of great interest in basic
      and clinical research. The analyses of DNA methylation and hydroxymethylation
      patterns in body fluids might allow one to determine the certain state of a
      disease, in particular of cancer. DNA methylation biomarkers in liquid biopsies,
      i.e. blood plasma samples, may help optimizing personalized therapy for
      individual patients. DNA methylation analyses of specific loci usually require a
      bisulfite conversion of the DNA, which requires a sufficiently high amount of DNA
      at the appropriate concentration. However, free-circulating DNA is generally low
      concentrated. Therefore, high volumes of body fluids need to be analyzed. This
      high volume needs to be reduced in order to facilitate the bisulfite conversion.
      In addition, disease-related free-circulating DNA is even less abundant than
      normal DNA in the total amount of free-circulating DNA. Accordingly, analytical
      and pre-analytical methods are needed, which permit an accurate and sensitive
      quantification of single methylated DNA copies in the presence of unmethylated
      DNA in abundance.This protocol describes two methods for DNA enrichment from body
      fluids: DNA extraction by means of magnetic beads and polymer-mediated enrichment
      of DNA. Subsequent bisulfite conversion is achieved by means of a high-speed
      conversion protocol. Adaptions of the workflow required for the analysis of
      hydroxymethylation via oxidation 5-hydroxymethylcytosines to 5-formylcytosines
      prior to the bisulfite conversion are introduced. A quantitative real-time PCR
      based on the methylation-specific and HeavyMethyl PCR methodologies is
      introduced. This qPCR assay allows for an accurate and sensitive quantification
      of single copies of the DNA methylation biomarkers SHOX2 and SEPT9 in blood
      plasma. Specific issues regarding the analysis of body fluids and respective
      trouble shooting approaches are discussed.

PMID- 29224168
TI  - Tet-Assisted Bisulfite Sequencing (TAB-seq).
AB  - 5-Hydroxymethylcytosine (5hmC) is a modified form of cytosine, which has recently
      been found in mammalian cells and tissues. 5hmC is derived from 5-methylcytosine
      (5mC) by Ten-eleven translocation (TET) family protein-mediated oxidation and may
      regulate gene expression. Numerous affinity-based profiling methods have been
      developed to help understand the exact function of 5hmC in the genome. However,
      these methods have a relatively low resolution (~100 bp) without quantitative
      information of the modification percentage on each site. Here we demonstrated the
      detailed procedure of Tet-Assistant Bisulfite Sequencing (TAB-Seq), which can
      detect 5hmC at single-base resolution and quantify its abundance at each site. In
      this protocol, the genomic DNA is first treated with betaGT and recombinant mTet1
      consecutively to convert 5hmC to 5gmC and 5mC to 5caC, respectively. The treated
      genomic DNA can be directly applied to bisulfite treatment to detect 5hmC on
      specific loci or applied to whole-genome bisulfite sequencing as needed.

PMID- 29224169
TI  - Multiplexing for Oxidative Bisulfite Sequencing (oxBS-seq).
AB  - DNA modifications, especially methylation, are known to play a crucial part in
      many regulatory processes in the cell. Recently, 5-hydroxymethylcytosine (5hmC)
      was discovered, a DNA modification derived as an intermediate of 5-methylcytosine
      (5mC) oxidation. Efforts to gain insights into function of this DNA modification
      are underway and several methods were recently described to assess 5hmC levels
      using sequencing approaches. Here we integrate adaptation based multiplexing and
      high-efficiency library prep into the oxidative Bisulfite Sequencing (oxBS-seq)
      workflow reducing the starting amount and cost per sample to identify 5hmC levels
      genome-wide.

PMID- 29224170
TI  - Affinity-Based Enrichment Techniques for the Genome-Wide Analysis of 5
      Hydroxymethylcytosine.
AB  - Since its initial characterization in 2009 there has been a great degree of
      interest in comparative profiling of 5-hydroxymethylcytosine (5hmC) nucleotides
      in vertebrate DNA. Through a host of genome-wide studies the distribution of 5hmC
      has been mapped in a range of cell lines, tissue types and organisms; the
      majority of which have been generated through affinity-based methods for 5hmC
      enrichment. Although recent advances in the field have resulted in the ability to
      investigate the levels of both methylated and hydroxymethylated cytosines at
      single base resolution, such studies are still relatively cost-prohibitive as
      well as technically challenging. As such affinity-based methods for the
      enrichment of 5hmC-modified DNA fragments represent a cost-effective and highly
      informative method for profiling 5hmC residency in genomic DNA. Here we will
      outline protocols for two independent affinity based methods to generate 5hmC
      enriched fractions for subsequent locus specific and genome-wide analysis;
      immunoprecipitation using highly specific 5hmC antibodies as well as a chemical
      capture based method.

PMID- 29224171
TI  - Genetic mapping and validation of the loci controlling 7S alpha' and 11S A-type
      storage protein subunits in soybean [Glycine max (L.) Merr.].
AB  - KEY MESSAGE: Four soybean storage protein subunit QTLs were mapped using bulked
      segregant analysis and an F2 population, which were validated with an F5 RIL
      population. The storage protein globulins beta-conglycinin (7S subunit) and
      glycinin (11S subunits) can affect the quantity and quality of proteins found in
      soybean seeds and account for more than 70% of the total soybean protein.
      Manipulating the storage protein subunits to enhance soymeal nutrition and for
      desirable tofu manufacturing characteristics are two end-use quality goals in
      soybean breeding programs. To aid in developing soybean cultivars with desired
      seed composition, an F2 mapping population (n = 448) and an F5 RIL population (n
      = 180) were developed by crossing high protein cultivar 'Harovinton' with the
      breeding line SQ97-0263_3-1a, which lacks the 7S alpha', 11S A1, 11S A2, 11S A3
      and 11S A4 subunits. The storage protein composition of each individual in the F2
      and F5 populations were profiled using SDS-PAGE. Based on the presence/absence of
      the subunits, genomic DNA bulks were formed among the F2 plants to identify
      genomic regions controlling the 7S alpha' and 11S protein subunits. By utilizing
      polymorphic SNPs between the bulks characterized with Illumina SoySNP50K iSelect
      BeadChips at targeted genomic regions, KASP assays were designed and used to map
      QTLs causing the loss of the subunits. Soybean storage protein QTLs were
      identified on Chromosome 3 (11S A1), Chromosome 10 (7S alpha' and 11S A4), and
      Chromosome 13 (11S A3), which were also validated in the F5 RIL population. The
      results of this research could allow for the deployment of marker-assisted
      selection for desired storage protein subunits by screening breeding populations
      using the SNPs linked with the subunits of interest.

PMID- 29224172
TI  - Evaluation of clinical risk factors for osteoporosis and applicability of the
      FRAX tool in Joinville City, Southern Brazil.
AB  - : Clinical risk factors for fracture in Southern Brazil are similar to those used
      in Fracture Risk Assessment Tool (FRAX(r)). Age-dependent intervention thresholds
      had higher accuracy than a fixed cut-off point. INTRODUCTION: Access to bone
      mineral density testing is wanted for a large part of the Brazilian population.
      The FRAX(r) has an option to calculate the risk of fracture without this costly
      evaluation but relies on the clinical risk factors (CRFs) identified in the
      source cohorts used to generate FRAX. OBJECTIVE: The aims of this study were to
      determine whether the CRFs used in FRAX are also risk indicators for individuals
      in Southern Brazil and to evaluate possible intervention thresholds for treatment
      in Brazil. METHODS: We determined the CRFs for hip fractures in women and men
      aged 50 years and more with a hip fracture and controls in Joinville, Southern
      Brazil (April 1, 2010, and March 31, 2012). For intervention thresholds, we
      determined the accuracy of using the fixed thresholds of National Osteoporosis
      Foundation (NOF), USA, compared with the age-dependent thresholds of the National
      Osteoporosis Guideline Group (NOGG), UK. RESULTS: CRFs that were significant for
      hip fracture were very similar to FRAX, apart from chronic obstructive pulmonary
      disease and malabsorptive intestinal disease. FRAX based on the NOGG and NOF
      models had an accuracy of 64.2 and 58.7%, respectively. CONCLUSION: CRFs used in
      FRAX(r) were similar to those in the Southern Brazil. The NOGG model seems to be
      more accurate to discriminate patients with increased fracture risk in this
      population compared to the NOF model, but not significantly.

PMID- 29224173
TI  - Testing the specificity of executive functioning impairments in adolescents with
      ADHD, ODD/CD and ASD.
AB  - Current diagnostic systems conceptualise attention deficit hyperactivity disorder
      (ADHD), oppositional defiant/conduct disorder (ODD/CD) and autism spectrum
      disorder (ASD) as separate diagnoses. However, all three demonstrate executive
      functioning (EF) impairments. Whether these impairments are trans-diagnostic or
      disorder-specific remains relatively unexplored. Four groups of 10-16 year-olds
      [typically developing (TD; N = 43), individuals clinically diagnosed with ADHD (N
      = 21), ODD/CD (N = 26) and ASD (N = 41)] completed Go/NoGo and Switch tasks.
      Group differences were tested using analysis of co-variance (ANCOVA) including
      age, IQ, sex, conduct problems and ADHD symptoms as co-variates. Results
      indicated some disorder-specificity as only the ASD group demonstrated decreased
      probability of inhibition in the Go/NoGo task compared to all other groups.
      However, shared impairments were also found; all three diagnostic groups
      demonstrated increased reaction time variability (RTV) compared to the TD group,
      and both the ODD/CD and the ASD group demonstrated increased premature responses.
      When controlling for ADHD symptoms and conduct problems, group differences in RTV
      were no longer significant; however, the ASD group continued to demonstrate
      increased premature responses. No group differences were found in cognitive
      flexibility in the Switch task. A more varied response style was present across
      all clinical groups, although this appeared to be accounted for by sub-threshold
      ODD/CD and ADHD symptoms. Only the ASD group was impaired in response inhibition
      and premature responsiveness relative to TD adolescents. The findings suggest
      that some EF impairments typically associated with ADHD may also be found in
      individuals with ASD.

PMID- 29224175
TI  - Thalamic interactions of cerebellum and basal ganglia.
AB  - Cerebellum and basal ganglia are reciprocally interconnected with the neocortex
      via oligosynaptic loops. The signal pathways of these loops predominantly
      converge in motor areas of the frontal cortex and are mainly segregated on
      subcortical level. Recent evidence, however, indicates subcortical interaction of
      these systems. We have reviewed literature that addresses the question whether,
      and to what extent, projections of main output nuclei of basal ganglia (reticular
      part of the substantia nigra, internal segment of the globus pallidus) and
      cerebellum (deep cerebellar nuclei) interact with each other in the thalamus. To
      this end, we compiled data from electrophysiological and anatomical studies in
      rats, cats, dogs, and non-human primates. Evidence suggests the existence of
      convergence of thalamic projections originating in basal ganglia and cerebellum,
      albeit sparse and restricted to certain regions. Four regions come into question
      to contain converging inputs: (1) lateral parts of medial dorsal nucleus (MD);
      (2) parts of anterior intralaminar nuclei and centromedian and parafascicular
      nuclei (CM/Pf); (3) ventromedial nucleus (VM); and (4) border regions of
      cerebellar and ganglia terminal territories in ventral anterior and ventral
      lateral nuclei (VA-VL). The amount of convergences was found to exhibit marked
      interspecies differences. To explain the rather sparse convergences of projection
      territories and to estimate their physiological relevance, we present two
      conceivable principles of anatomical organization: (1) a "core-and-shell"
      organization, in which a central core is exclusive to one projection system,
      while peripheral shell regions intermingle and occasionally converge with other
      projection systems and (2) convergences that are characteristic to distinct
      functional networks. The physiological relevance of these convergences is not yet
      clear. An oculomotor network proposed in this work is an interesting candidate to
      examine potential ganglia and cerebellar subcortical interactions.

PMID- 29224174
TI  - Cost-Effectiveness of Treatments for the Management of Bone Metastases: A
      Systematic Literature Review.
AB  - BACKGROUND: Metastatic cancers occur when cancer cells break away from the
      primary tumour. One of the most common sites of metastasis is the bone, with
      several therapeutic options currently available for managing bone metastases. In
      a resource-constrained environment, policy makers and practitioners need to know
      which options are cost effective. OBJECTIVE: The aim of this systematic review
      was to review and appraise published economic evaluations on treatments for the
      management of bone metastases. METHODS: We searched eight bibliographic databases
      (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant
      economic evaluations published from each database's inception date until March
      2017. Study selection, quality assessment and data extraction were carried out
      according to published guidelines. RESULTS: Twenty-four relevant economic
      analyses were identified. Seventeen of these studies focused on bone metastases
      resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n =
      7), lung (n = 1) or renal (n = 1), while seven report results for various primary
      tumours. Across types of cancer, evidence suggests that bisphosphonates result in
      lower morbidity and improved quality of life, for an additional cost, which is
      typically below conventional cost-effectiveness thresholds. While denosumab leads
      to health gains compared with zoledronic acid, it also results in substantial
      additional costs and is unlikely to represent value for money. The limited
      literature on the radiopharmaceutical strontium-89 (Sr89) and external beam
      radiotherapy (EBR) suggest that these treatments are cost effective compared with
      no treatment. CONCLUSIONS: The reviewed evidence suggests that bisphosphonate
      treatments are cost-effective options for bone metastases, while denosumab is
      unlikely to represent value for money. Evidence on EBR and Sr89 is limited and
      less conclusive.

PMID- 29224176
TI  - Validation of a method for estimating energy expenditure during walking in middle
      aged adults.
AB  - PURPOSE: The aim of this study was to test the validity of a method using an
      inertial measurement unit for estimating activity-related energy expenditure
      (AEE) during walking in middle-aged adults. METHODS: Twenty healthy middle-aged
      participants completed different treadmill walking trials with an inertial
      measurement unit adhered to their lower back. Gas exchange was monitored with
      indirect calorimetry. Mechanical data were used to estimate AEE from an algorithm
      developed by Bouten et al. (Med Sci Sport Exer 26(12):1516-1523, 1994). Three
      methods for removing the gravitational component were proposed and tested: mean
      subtraction method (MSM), high-pass filter method (HPM) and free acceleration
      method (FAM). RESULTS: The three methods did not differ significantly from the
      indirect calorimetry [bias = - 0.08 kcal min-1; p = 0.47 (MSM), bias = - 0.08
      kcal min-1; p = 0.48 (HPM) and bias = - 0.15 kcal min-1; p = 0.23 (FAM)]. Mean
      root mean square errors were 0.43, 0.42 and 0.51 kcal min-1 for MSM, HPM and FAM,
      respectively. CONCLUSION: This study proposed an accurate method for estimating
      AEE in middle-aged adults for a large range of walking intensities, from slow to
      brisk walking, based on Bouten's algorithm.

PMID- 29224177
TI  - Thinking about one's own death after prostate-cancer diagnosis.
AB  - BACKGROUND: Prostate-cancer diagnosis increases the risk for psychiatric
      morbidity and suicide. Thoughts about one's own death could indicate need for
      psychiatric care among men with localized prostate cancer. We studied the
      prevalence and predictors of thoughts about own death among men with prostate
      cancer. METHODS: Of the 3930 men in the prospective, multi-centre LAPPRO-trial,
      having radical prostatectomy, 3154 (80%) answered two study-specific
      questionnaires, before and three months after surgery. Multivariable prognostic
      models were built with stepwise regression and Bayesian Model Averaging. RESULTS:
      After surgery 46% had thoughts about their own death. Extra-prostatic tumor
      growth [Adjusted Odds-Ratio 2.06, 95% Confidence Interval 1.66-2.56], university
      education [OR 1.66, CI 1.35-2.05], uncertainty [OR 2.20, CI 1.73-2.82], low
      control [OR 2.21, CI 1.68-2.91], loneliness [OR 1.75, CI 1.30-2.35], being a
      burden [OR 1.59, CI 1.23-2.07], and crying [OR 1.55, CI 1.23-1.96] before surgery
      predicted thoughts about one's own death after surgery. CONCLUSIONS: We
      identified predictors for thoughts about one's own death after prostate cancer
      diagnosis and surgery. These factors may facilitate the identification of
      psychiatric morbidity and those who might benefit from psychosocial support
      already during primary treatment.

PMID- 29224178
TI  - Evaluation of the anti-inflammatory and urotoxicity ameliorative effects of gamma
      humulene containing active fraction of Emilia sonchifolia (L.) DC.
AB  - In folklore medicine, the plant Emilia sonchifolia, belonging to the family
      Asteraceae, is used for treating tumour and inflammation. In our previous
      studies, we have done a thorough phytochemical investigation of E. sonchifolia
      with a report on its potent antimetastatic activity. Further, we isolated and
      characterised its active fraction (AFES) containing the major compound gamma
      humulene with an evaluation of the antiangiogenic effect of AFES (5 mg/kg b.wt.).
      In the first part of the present study, AFES in different concentrations was used
      for the assessment of its possible anti-inflammatory effect employing three in
      vivo inflammatory models. Further using the most effective concentration of AFES
      5 mg/kg b.wt, its effect on proinflammatory cytokine levels was recorded along
      with a confirmatory gene expression analysis. The results manifested with a
      reduction in the paw oedema significantly decreased levels of proinflammatory
      cytokines, C-reactive protein, nitric oxide and also there was an efficient
      downregulation of cyclooxygenase-2 and inducible nitric oxide. Urotoxicity is one
      of the major side effects of conventional chemotherapy. So in the second part of
      the study, we used AFES in combination with the conventional therapeutic agent
      cyclophosphamide in vivo in mice. The effect of AFES on urotoxicity was assessed
      from various biochemical parameters, cytokine markers and finally with a
      histopathology of the bladder. The current study revealed the protective effects
      of AFES, implicating reduced levels of urea nitrogen, by revamping of glutathione
      and marker cytokine levels towards positive amelioration. The results obtained
      altogether proved the safeguarding effect of AFES in murine experimental models.

PMID- 29224180
TI  - Evaluation of a rapid immunochromatographic test for the detection of low burden
      Dirofilaria immitis (heartworm) in dogs and cats.
AB  - The performance of a rapid immunochromatographic test for the detection of
      Dirofilaria immitis antigens (Speed DiroTM; BVT-Virbac, France) was assessed in
      49 experimentally infected dogs and in 244 naturally infected animals; 142 dogs
      and 102 cats. In experimentally infected dogs, Speed DiroTM showed a sensitivity
      of 90.9% in dogs infected with one adult female worm and 100% in dogs infected
      with more than one female worm. Specificity was 100%. For naturally infected
      dogs, the Knott test and PetChek(r) HTWM PF served as reference methods for
      microfilaremia and antigenemia, respectively. All microfilaemic dogs (55/142)
      were positive with Speed DiroTM. Importantly, none of the 21 dogs infected with
      D. repens were positive. The results of Speed DiroTM for the detection of
      antigenemia were compared with two in-house tests, SNAP(r) HTWM and Witness(r)
      Dirofilaria, and all three tests were 100% specific and sensitive in comparison
      to PetChek(r) HTWM PF. For the evaluation of feline samples, 102 cats were
      examined by echocardiography. Sera from 87 heartworm-infected cats were tested by
      Speed DiroTM and SNAP(r) HTWM. The results of Speed DiroTM were equivalent to
      SNAP(r) HTWM, with a sensitivity of 98.9% and a specificity of 100%.

PMID- 29224179
TI  - Antidiabetic Polypill Improves Central Pathology and Cognitive Impairment in a
      Mixed Model of Alzheimer's Disease and Type 2 Diabetes.
AB  - Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being
      Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely
      related to aging and with a growing elderly population it might be of relevance
      to explore new therapeutic approaches that may slow or prevent central
      complications associated with metabolic disorders. Therefore, we propose the use
      of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by
      T2D patients that include metformin, aspirin, simvastatin, and an angiotensin
      converting enzyme inhibitor. In order to test the effects of PP at the central
      level, we have long-term treated a new mixed model of AD-T2D, the APP/PS1xdb/db
      mouse. We have analyzed AD pathological features and the underlying specific
      characteristics that relate AD and T2D. As expected, metabolic alterations were
      ameliorated after PP treatment in diabetic mice, supporting a role for PP in
      maintaining pancreatic activity. At central level, PP reduced T2D-associated
      brain atrophy, showing both neuronal and synaptic preservation. Tau and amyloid
      pathologies were also reduced after PP treatment. Furthermore, we observed a
      reduction of spontaneous central bleeding and inflammation after PP treatment in
      diabetic mice. As consequence, learning and memory processes were improved after
      PP treatment in AD, T2D, and AD-T2D mice. Our data provide the basis to further
      analyze the role of PP, as an alternative or adjuvant, to slow down or delay the
      central complications associated with T2D and AD.

PMID- 29224181
TI  - Social cognition and aggression in methamphetamine dependence with and without a
      history of psychosis.
AB  - In substance use and psychotic disorders, socially problematic behaviours, such
      as high aggression may, in part, be explained by deficits in social cognition
      skills, like the detection of emotions or intentions in others. The aim of this
      study was to assess the magnitude of social cognition impairment and its
      association with aggression in individuals with methamphetamine (MA) dependence,
      methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total
      of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21
      CTRL participants performed a facial morphing emotion recognition task (ERT)
      across four basic emotions (anger, fear, happiness and sadness) and the reading
      the mind in the eyes task (RMET), and completed the aggression questionnaire.
      Both MA-dependent groups showed impairment in social cognition in terms of lower
      RMET scores relative to CTRL participants (MA; p = .047; MAP: p < .001).
      Additionally, performance decrements were significantly greater in MAP (p =
      .040), compared to MA-dependent participants. While deficits in recognising
      emotional expressions were restricted to anger in the MA group (p = .020), a
      generalized impairment across all four emotions was observed in MAP (all p <=
      .001). Additionally, both patient groups demonstrated higher levels of aggression
      than CTRLs, yet no association was found with social cognition. This study
      supported the notion of deficits in recognising facial emotional expressions and
      inferring mental states of others in MA dependence, with additional impairments
      in MAP. Failure to detect an association between social cognitive impairment and
      aggressive behaviour may implicate independent disturbances of the two phenomena
      in MA dependence.

PMID- 29224182
TI  - Stable and rigid DTPA-like paramagnetic tags suitable for in vitro and in situ
      protein NMR analysis.
AB  - Organic synthesis of a ligand with high binding affinities for paramagnetic
      lanthanide ions is an effective way of generating paramagnetic effects on
      proteins. These paramagnetic effects manifested in high-resolution NMR
      spectroscopy are valuable dynamic and structural restraints of proteins and
      protein-ligand complexes. A paramagnetic tag generally contains a metal chelating
      moiety and a reactive group for protein modification. Herein we report two new
      DTPA-like tags, 4PS-PyDTTA and 4PS-6M-PyDTTA that can be site-specifically
      attached to a protein with a stable thioether bond. Both protein-tag adducts form
      stable lanthanide complexes, of which the binding affinities and paramagnetic
      tensors are tunable with respect to the 6-methyl group in pyridine. Paramagnetic
      relaxation enhancement (PRE) effects of Gd(III) complex on protein-tag adducts
      were evaluated in comparison with pseudocontact shift (PCS), and the results
      indicated that both 4PS-PyDTTA and 4PS-6M-PyDTTA tags are rigid and present high
      quality PREs that are crucially important in elucidation of the dynamics and
      interactions of proteins and protein-ligand complexes. We also show that these
      two tags are suitable for in-situ protein NMR analysis.

PMID- 29224184
TI  - Experimental validation of the diffusion model based on a slow response time
      paradigm.
AB  - The diffusion model (Ratcliff, Psychol Rev 85(2):59-108, 1978) is a stochastic
      model that is applied to response time (RT) data from binary decision tasks. The
      model is often used to disentangle different cognitive processes. The validity of
      the diffusion model parameters has, however, rarely been examined. Only few
      experimental paradigms have been analyzed with those being restricted to fast
      response time paradigms. This is attributable to a recommendation stated
      repeatedly in the diffusion model literature to restrict applications to fast RT
      paradigms (more specifically, to tasks with mean RTs below 1.5 s per trial). We
      conducted experimental validation studies in which we challenged the necessity of
      this restriction. We used a binary task that features RTs of several seconds per
      trial and experimentally examined the convergent and discriminant validity of the
      four main diffusion model parameters. More precisely, in three experiments, we
      selectively manipulated these parameters, using a difficulty manipulation (drift
      rate), speed-accuracy instructions (threshold separation), a more complex motoric
      task (non-decision time), and an asymmetric payoff matrix (starting point). The
      results were similar to the findings from experimental validation studies based
      on fast RT paradigms. Thus, our experiments support the validity of the
      parameters of the diffusion model and speak in favor of an extension of the model
      to paradigms based on slower RTs.

PMID- 29224183
TI  - Effects of Acute Alcohol Exposure on Layer 5 Pyramidal Neurons of Juvenile Mice.
AB  - Early-onset drinking during childhood or preadolescence is a serious social
      problem. Yet, most of the basic neurobiological research on the acute effects of
      ethanol has been carried out on adult or early postnatal animals. We studied the
      effect of alcohol exposure on the basic electrophysiological properties and cell
      viability of layer 5 pyramidal neurons from the somatosensory cortex of juvenile
      (P21-P23) C57BL/6N mice. After bath application of 50 mM ethanol to acute slices
      of the somatosensory cortex, no adverse effects were detected on cells survival,
      whereas the input resistance and firing rate of layer 5 neurons were
      significantly reduced. While the effect on the input resistance was reversible,
      the depressing effect on cell firing remained stable after 6 min of alcohol
      exposure. Ethanol application did not result in any significant change of mIPSC
      frequency, amplitude, and rise time. A slight increase of mIPSC decay time was
      observed after 6 min of ethanol exposure. The molecular mechanisms leading to
      these alterations and their significance for the physiology of the cerebral
      cortex are briefly discussed.

PMID- 29224185
TI  - Tension force-induced bone formation in orthodontic tooth movement via modulation
      of the GSK-3beta/beta-catenin signaling pathway.
AB  - Orthodontic force-induced osteogenic differentiation and bone formation at
      tension sites play a critical role in orthodontic tooth movement. However, the
      molecular mechanism underlying this phenomenon is poorly understood. In the
      current study, we investigated the involvement of the GSK-3beta/beta-catenin
      signaling pathway, which is critical for bone formation during tooth movement. We
      established a rat tooth movement model to test the hypothesis that orthodontic
      force may stimulate bone formation at the tension site of the moved tooth and
      promote the rate of tooth movement via regulation of the GSK-3beta/beta-catenin
      signaling pathway. Our results showed that continued mechanical loading increased
      the distance between the first and second molar in rats. In addition, the loading
      force increased bone formation at the tension site, and also increased phospho
      Ser9-GSK-3beta expression and beta-catenin signaling pathway activity.
      Downregulation of GSK-3beta activity further increased bone parameters, including
      bone mineral density, bone volume to tissue volume and trabecular thickness, as
      well as ALP- and osterix-positive cells at tension sites during tooth movement.
      However, ICG-001, the beta-catenin selective inhibitor, reversed the positive
      effects of GSK-3beta inhibition. In addition, pharmaceutical inhibition of GSK
      3beta or local treatment with beta-catenin inhibitor did not influence the rate
      of tooth movement. Based on these results, we concluded that GSK-3beta/beta
      catenin signaling contributes to the bone remodeling induced by orthodontic
      forces, and can be used as a potential therapeutic target in clinical dentistry.

PMID- 29224186
TI  - Secondhand smoke is associated with heavy metal concentrations in children.
AB  - : Secondhand smoke (SHS) has adverse effects on health, particularly for
      children. Our purpose was to analyze the correlation between SHS exposure and
      heavy metal concentrations in children. The investigation was conducted in
      Xinxiang County, Henan Province, China, from August 2015 to December 2015. In
      total, 821 students (433 boys and 388 girls) were recruited, and the contents of
      heavy metals in their hair-including chromium, manganese, nickel, arsenic, lead,
      and cadmium-were detected by ICP-MS. The children's parents were informed, and a
      questionnaire was conducted, which included questions about smoking habits and
      demographic characteristics. Our results indicate that all parent smokers are
      fathers, 48.9% of fathers who are smokers, but 25.2% of fathers smoke in front of
      their children. The levels of chromium (median girls vs boys, MUg/g) (2.36 vs
      2.06, p < 0.001), nickel (1.28 vs 0.97, p < 0.001), arsenic (0.55 vs 0.49, p <
      0.001), and lead (2.73 vs 2.16, p < 0.001) in girls were significantly higher
      than in boys. The levels of cadmium (median, SHS group vs control: 0.43 vs 0.29
      (MUg/g), p < 0.001) and lead (median, SHS group vs control: 2.71 vs 2.27 (MUg/g),
      p = 0.007) in the SHS group were significantly higher than in the control. Multi
      linear regression analysis indicated that SHS exposure in children is very likely
      to be correlated with increasing levels of lead (beta (95% CI): 0.53 (0.99-5.14),
      p = 0.023) and cadmium (beta (95% CI): 0.43 (0.14-0.73), p = 0.003) in their
      hair. In conclusion, children exposed to SHS have increased lead and cadmium
      accumulations in the body. CONCLUSION: In our study, 821 students (433 boys and
      388 girls) were recruited, and the contents of heavy metals in their hair
      including chromium, manganese, nickel, arsenic, lead, and cadmium-were detected
      by ICP-MS. And the secondhand smoking (SHS) exposure was inquired by face-to-face
      investigation of their parents. We illustrated that children exposed to SHS have
      increased lead and cadmium accumulations in the body. What is Known: * Secondhand
      smoke (SHS) has adverse effects on health, particularly for children. * There
      might be correlation between SHS exposure and heavy metal concentrations in
      children. What is New: * The levels of chromium, nickel, arsenic, and lead in
      girls were significantly higher than in boys. * SHS exposure in children was
      correlated with increasing levels of lead and cadmium in their hair because of
      exposure to SHS.

PMID- 29224187
TI  - Surma eye cosmetic in Afghanistan: a potential source of lead toxicity in
      children.
AB  - : Surma is a traditional eye cosmetic used as an eyeliner for infants in
      Afghanistan, as well as in many other countries in Asia, the Middle East, and
      Africa. Surma has been reported to contain lead and to be a potential source of
      lead toxicity in children, which can lead to permanent damage to multiple organ
      systems. To our knowledge, assessment for lead in surma found in Afghanistan has
      not been performed. We determined the quantitative lead content of a convenience
      sample of 10 surma products acquired in Afghanistan. Analysis revealed that 70%
      of surma samples contained high levels of lead (range 35-83%). The remaining
      samples contained low levels of lead (range 0.04-0.17%). CONCLUSION: The majority
      of surma samples contained very high levels of lead, a troubling finding that
      could potentially correlate with lead toxicity in Afghan children. Making
      available lead-free surma alternatives and providing health education, for both
      healthcare professionals and the general population, in locations where surma use
      is prevalent and for those involved in care of refugees and immigrants from
      Afghanistan, may be strategies to prevent lead poisoning in children. What is
      Known: * Surma is a traditional cosmetic used as an eyeliner for infants in
      Afghanistan as well as in many countries in Asia, the Middle East, and Africa. *
      Surma has been reported to contain lead and to be a source of lead toxicity in
      children. What is New: * Assessment for lead content in surma found in
      Afghanistan has not been performed. * In this convenience sample of 10 surma
      products acquired in Afghanistan, 70% contained very high levels of lead.

PMID- 29224188
TI  - An Evaluation of a Social Skills Intervention for Adults with Autism Spectrum
      Disorder and Intellectual Disabilities preparing for Employment in Ireland: A
      Pilot Study.
AB  - Individuals with autism spectrum disorder (ASD) are faced with significant
      barriers relating to employment opportunities and workplace participation. This
      study evaluated the effectiveness of the Walker social skills curriculum: the
      ACCESS program and video modeling to increase social communication skills
      necessary for workplace inclusion. Participants attended two sessions (i.e., 3 h)
      per week across a period of 20 weeks. A multiple-probe design was used to
      demonstrate social skills outcomes across three broad curricular areas (i.e.,
      peer-related, adult-related, and self-related social skills). Pre-and post
      intervention standardized assessments were also taken. Results showed significant
      increases in target social skills and a significant decrease in problem behaviors
      following intervention. Evidence of maintenance and generalization were also
      demonstrated. Implications for practice and research are discussed.

PMID- 29224193
TI  - Screening of yeasts for the production of 2-phenylethanol (rose aroma) in organic
      waste-based media.
AB  - : In this study, we isolated 28 yeast strains from samples of plant material and
      fermented food and evaluated the possibility of efficient production of 2
      phenylethanol (2-PE) in the organic waste-based media supplemented with l
      phenylalanine (l-Phe). We used whey, a by-product from milk processing, as a base
      for media, and either glucose or three by-products from sugar beet processing as
      a fermentable carbon source. Ten newly isolated yeast strains were capable of
      producing over 2 g l-1 2-PE through the l-Phe biotransformation in a batch mode
      in standard medium. Among them, we selected eight strains producing 2-PE in a
      range of 1.17-3.28 g l-1 in 72 h batch cultures in shaking flasks in whey-based
      media. The strains were assigned to five species of Meyerozyma caribbica,
      Metschnikowia chrysoperlae, Meyerozyma guilliermondii, Pichia fermentans and
      Saccharomyces cerevisiae. While S. cerevisiae is known to be a promising producer
      of 2-PE, the four latter species are poorly studied on this application. Results
      presented here are better than other reported values for batch cultures of
      unmodified yeast strains. Therefore, it seems that whey and by-products from
      sugar beet processing might be a good feedstock for 2-PE bioproduction.
      SIGNIFICANCE AND IMPACT OF THE STUDY: 2-Phenylethanol (2-PE) is an alcohol with a
      pleasant rosy scent, which is commonly used in the food, fragrance and cosmetic
      industries as an aroma compound and preservative. Promising sources of 2-PE are
      yeasts, but still the biotechnological route has not been economically
      competitive to chemical synthesis. Thus, the first challenging goal to develop
      biotechnological production of 2-PE is the identification of highly productive
      yeasts and cheap feedstock. This study demonstrates for the first time the
      promising production of 2-PE by selected yeasts in organic waste-based media.
      This could pave the way for development of a cheaper method of 2-PE
      bioproduction.

PMID- 29224189
TI  - Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic
      deterioration in mice.
AB  - AIM/HYPOTHESIS: Adiponectin (APN), a circulating hormone secreted by mature
      adipocytes, has been extensively studied because it has beneficial metabolic
      effects. While many studies have focused on the congenital loss of APN and its
      effects on systemic body glucose and lipid metabolism, little is known about the
      effects triggered by acute loss of APN in the adult mouse. We anticipated that
      genetically induced acute depletion of APN in adult mice would have a more
      profound effect on systemic metabolic health than congenital deletion of Adipoq,
      the gene encoding APN, with its associated potential for adaptive responses that
      may mask the phenotypes. METHODS: Mice carrying loxP-flanked regions of Adipoq
      were generated and bred to the Adipoq (APN) promoter-driven reverse tetracycline
      controlled transactivator (rtTA) (APN-rtTA) gene and a tet-responsive Cre line
      (TRE-Cre) to achieve acute depletion of APN. Upon acute removal of APN in adult
      mice, systemic glucose and lipid homeostasis were assessed under basal and
      insulinopenic conditions. RESULTS: The acute depletion of APN results in more
      severe systemic insulin resistance and hyperlipidaemia than in mice with
      congenital loss of APN. Furthermore, the acute depletion of APN in adult mice
      results in a much more dramatic reduction in survival rate, with 50% of inducible
      knockouts dying in the first 5 days under insulinopenic conditions compared with
      0% of congenital Adipoq knockout mice under similar conditions.
      CONCLUSIONS/INTERPRETATION: Acute systemic removal of APN results in a much more
      negative metabolic phenotype compared with congenital knockout of Adipoq.
      Specifically, our data demonstrate that acute depletion of APN is especially
      detrimental to lipid homeostasis, both under basal and insulinopenic conditions.
      This suggests that compensatory mechanisms exist in congenital knockout mice that
      offset some of the metabolic actions covered by APN.

PMID- 29224197
TI  - Collecting patient-reported outcome measures.
AB  - Patient-reported outcome measures (PROM) are potentially useful outcome measures
      that may be reported at the individual clinical, health service and/or health
      system level. PROM require clearly defined patient populations to enable
      comparisons, and are most meaningful when integrated with clinical data sets.
      Where possible PROM should be measured pre- and post-intervention using reliable
      and validated tools. A variety of PROM collection methods exist which each have
      strengths and limitations, with selection depending on their purpose and patient
      factors. PROM programmes should be developed with high levels of clinician
      support and patient input to maximise collection of clinically relevant
      information.

PMID- 29224191
TI  - Bilateral choroiditis as the only sign of persistent Mycobacterium intracellulare
      infection following haematogenous spread in an immunocompromised patient.
AB  - An immunocompromised patient had positive blood cultures for Mycobacterium
      intracellulare and no identifiable organ seeding was started on treatment. One
      month later, the patient was clinically well with negative blood cultures but
      drug-induced myelotoxicity had developed. Ocular fundus examination at this time
      revealed bilateral choroidal granulomas which changed patient management.

PMID- 29224196
TI  - Diagnostic accuracy of posterior cervical angle and cervical length in the
      prediction of successful induction of labor.
AB  - OBJECTIVE: To determine the accuracy of the posterior cervical angle (PCA)
      compared with the cervical length and the Bishop score in predicting the outcome
      of induction of labor (IOL). METHODS: The present prospective observational study
      included IOL candidates who had their PCA and cervical length assessed by
      transvaginal ultrasonography and the Bishop score at the Obstetrics and
      Gynecology Department, Kasr El-Aini Hospital, Cairo University, Cairo, Egypt,
      between April 1 and July 31, 2017. The accuracy of these tests in predicting
      successful IOL (defined as vaginal delivery) was compared. RESULTS: The analysis
      included 49 women with successful IOL and 21 women with unsuccessful IOL. The
      suggested cutoffs for the prediction of successful IOL were a PCA of more than
      99.5 degrees , a cervical length of less than 34 mm, and a Bishop score of more
      than five. The areas under the receiver operating characteristics curves for
      these three measures were not significantly different. However, a PCA of more
      than 99.5 degrees  had the best sensitivity (91.84%), specificity (90.48),
      positive predictive value (95.7%), negative predictive value (82.6%), positive
      likelihood ratio (9.64), and negative likelihood ratio (0.09) compared with the
      other two predictors. CONCLUSION: A PCA of more than 99.5 degrees  yielded the
      best accuracy in predicting successful IOL compared with the cervical length and
      the Bishop score. CLINICALTRIALS.GOV: NCT03113227.

PMID- 29224192
TI  - Short-term outcomes of arthroscopic TightRope(r) fixation are better than hook
      plate fixation in acute unstable acromioclavicular joint dislocations.
AB  - AIM: The aim of this study was to compare the short-term outcomes of arthroscopic
      TightRope(r) fixation with that of hook plate fixation in patients with acute
      unstable acromioclavicular joint dislocations. PATIENTS AND METHODS: We conducted
      a prospective case-control study of twenty-six patients with an acute ACJ
      dislocation who underwent surgical repair with either an arthroscopic
      TightRope(r) fixation or a hook plate from 2013 to 2016. Clinical and
      radiological data were collected prospectively. Clinical outcomes were evaluated
      using the Constant Score, the University of California at Los Angeles (UCLA)
      Shoulder Score, Oxford Shoulder Score as well as the visual analogue scale.
      Radiological outcomes were assessed with the coracoclavicular distance (CCD).
      RESULTS: Sixteen patients underwent arthroscopic TightRope(r) fixation, while 10
      patients underwent hook plate fixation. There were no significant differences in
      the preoperative variables except for the mean UCLA 4b infraspinatus score
      (TightRope(r) 2.8 vs. hook plate 3.8; p = 0.030). Duration of surgery was
      significantly longer in the TightRope(r) group. At 1 year post-operatively, the
      TightRope(r) group had a significantly better Constant Score and CCD with no
      complications. All patients with hook plate fixation had to undergo a second
      procedure for removal of implant, and 3 patients had complications. CONCLUSIONS:
      Arthroscopic TightRope(r) fixation is a good option for the treatment of acute
      unstable ACJ dislocations. It has better short-term clinical and radiological
      outcomes as well as lesser complications when compared to hook plate fixation.
      LEVEL OF EVIDENCE: Therapeutic, Level III.

PMID- 29224190
TI  - Metabolic surgery for the treatment of type 2 diabetes in obese individuals.
AB  - Several bariatric operations originally designed to promote weight loss have been
      found to powerfully treat type 2 diabetes, causing remission in most cases,
      through diverse mechanisms additional to the secondary consequences of weight
      loss. These observations have prompted consideration of such operations as
      'metabolic surgery', used expressly to treat diabetes, including among patients
      who are only mildly obese or merely overweight. Large, long-term observational
      studies consistently demonstrate that bariatric/metabolic surgery is associated
      with reductions in all cardiovascular risk factors, actual cardiovascular events,
      microvascular diabetes complications, cancer and death. Numerous recent
      randomised clinical trials, directly comparing various surgical vs non-surgical
      interventions for diabetes, uniformly demonstrate the former to be superior for
      improvements in all glycaemic variables, as well as other metabolic endpoints.
      These benefits are similar among individuals with type 2 diabetes and a
      preoperative BMI of 30-35 kg/m2 compared with traditional bariatric surgery
      patients with a BMI >35 kg/m2. The safety profiles of modern laparoscopic
      bariatric/metabolic operations are similar to those of elective laparoscopic
      hysterectomy and knee arthroplasty. However, more evidence regarding the risks,
      benefits and costs of surgery is needed from very long-term (>5 year) randomised
      clinical trials powered to observe 'hard' clinical endpoints following the
      operations most commonly used today. Given the efficacy, safety and cost
      effectiveness of metabolic surgery, the second Diabetes Surgery Summit (DSS-II)
      consensus conference recently placed surgery squarely within the overall diabetes
      treatment algorithm, recommending consideration of this approach for patients
      with inadequately controlled diabetes and a BMI as low as 30 kg/m2, or 27.5 kg/m2
      for Asian individuals. These new guidelines have been formally ratified by 53
      leading diabetes and surgery societies worldwide. Given this broad level of
      endorsement, we feel that the DSS-II recommendations should now replace the
      outdated National Institutes of Health (NIH) suggestions that have governed
      bariatric surgery practice and insurance compensation worldwide since 1991.

PMID- 29224194
TI  - Establishment and evaluation of an indirect immunofluorescence assay for the
      detection of salmonid alphavirus.
AB  - : Salmonid alphaviruses (SAV) severely infect farmed salmonids and rainbow trout.
      Owing to the recent increase in fish import trade, several SAV unreported
      countries, such as China, may face serious threat of this infection. Thus, it is
      necessary to develop efficient detection methods for the prevention and diagnosis
      of SAV infection. In this study, we selected a conserved segment of the SAV E1
      protein as a target immunogen for the preparation of monoclonal antibodies (mAbs)
      specific to SAV. A sensitive indirect immunofluorescence (IF) method was
      developed using 26E9C2 mAb that detected E1 protein and identified subtypes 1, 2
      and 5 of SAV. Thus, this assay provides a sensitive and specific detection
      method, and an improved technical support for the clinical diagnosis and
      epidemiological study of SAV. SIGNIFICANCE AND IMPACT OF THE STUDY: In this
      study, we successfully prepared two monoclonal antibodies (mAbs) against three
      subtypes of salmonid alphavirus (SAV), and established an indirect
      immunofluorescence assay that can be used to diagnose and prevent SAV from
      entering SAV unreported countries, such as China, through international trade.
      The application of this method will contribute to controlling SAV infection and
      reducing economic losses.

PMID- 29224195
TI  - Prevalence of soft tissue calcifications in the maxillofacial region detected by
      cone beam CT.
AB  - OBJECTIVE: To determine the prevalence of soft tissue calcifications in cone beam
      computed tomography (CBCT) scans with different fields of view (FOV) and to
      assess its relation with the clinical relevance of the CBCT findings. MATERIAL
      AND METHODS: One thousand CBCT scans were grouped according to FOV's size and
      region scanned (MX-FOV, maxilla; MD-FOV, mandible; and MM-FOV, maxilla/mandible)
      and evaluated for the presence of soft tissue calcifications. Laterality and
      length of the elongated styloid processes (ESP) were also assessed. RESULTS:
      Eight hundred and eighty-two soft tissue calcifications were detected in 626
      (62.6%) patients. MM-FOV presented the highest prevalence (76.8%), followed by MD
      FOV (60.6%) and MX-FOV (57.2%). ESP and tonsillolith were the most frequent
      calcifications. Calcifications requiring treatment or not and those in need of
      follow-up accounted for 6.9%, 92.7%, and 0.3% of cases, respectively. There was
      no association between calcifications and subjects' gender or age (p > .05). Most
      cases of ESP occurred bilaterally and were longer in males (p < .05).
      CONCLUSIONS: There is a high prevalence of soft tissue calcifications in CBCT,
      and ESP and tonsilloliths are the most common types in all evaluated FOVs. While
      most cases do not require treatment, we emphasize the importance of detailed CBCT
      assessment for its diagnosis.

PMID- 29224198
TI  - Interpreting insulin immunoassays during investigation of apparent spontaneous
      hypoglycaemia and insulin overdose.
AB  - We report two cases of hypoglycaemia; one with apparently spontaneous
      hypoglycaemia and one with presumed insulin overdose. In both cases insulin
      concentration was normal when measured with the Roche immunoassay, but elevated
      when remeasured with the Advia Centaur immunoassay and a diagnosis of
      hypoglycaemia secondary to insulin analogue administration was made. These cases
      highlight that physicians need to understand the binding characteristics of the
      insulin immunoassay they use.

PMID- 29224199
TI  - Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in
      inflammatory bowel disease patients.
AB  - Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in
      inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis
      or psoriasiform-like reactions are among the most common adverse reactions. We
      retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform
      manifestations in IBD patients at a tertiary centre in Australia. A total of 10
      (six females) of 270 (3.7%) IBD patients treated with anti-TNF therapy developed
      drug-induced psoriatic or psoriasiform-like reactions: five patients were treated
      with infliximab and five with adalimumab; nine had Crohn disease. The time from
      initiation of anti-TNF agent to onset of rash was 7.5 months on average. The most
      frequent distributions were the scalp (7/10) and extremities (6/10). Three
      patients discontinued anti-TNF treatment with resolution of the rash. Topical
      treatment of the lesions allowed continued use of biological agent in the
      majority. Paradoxical psoriatic lesions are recognised adverse events associated
      with anti-TNF therapy, but discontinuation of therapy due to dermatological
      complications is required only rarely, even in patients with psoriasiform
      lesions.

PMID- 29224200
TI  - Mortality in acute non-invasive ventilation.
AB  - A prospective study of non-invasive ventilation at The Prince Charles Hospital
      outside of the intensive care unit from March 2015 to March 2016 was performed.
      Overall 69 patients were included. Acute hypercapnic respiratory failure was the
      most common indication (n = 59; 85%). 49 (71%) had multifactorial respiratory
      failure. 15 (22%) patients died. Premorbid inability to perform self-care (P =
      0.001) and the combination of mean pH < 7.25 and mean PaCO2 >= 75 mmHg within 2 h
      of NIV initiation (P = 0.037) were significantly associated with mortality. There
      was a non-significant association between older age and mortality.

PMID- 29224201
TI  - Changing trends for diagnostic methods in Graves disease in Australia: an
      immunological diagnosis as the emerging preference.

PMID- 29224203
TI  - Temporal artery biopsy: time matters!

PMID- 29224204
TI  - Pleuroperitoneal Denver shunt insertion for the treatment of refractory
      chylothorax in a patient with tuberous sclerosis complex and
      lymphangioleiomyomatosis.

PMID- 29224205
TI  - Healthcare-acquired infections: prevention strategies.
AB  - Healthcare-acquired infections (HAI) impact on patient care and have cost
      implications for the Australian healthcare system. The management of HAI is
      exacerbated by rising rates of antimicrobial resistance (AMR). Health-care
      workers and a contaminated hospital environment are increasingly implicated in
      the transmission and persistence of multi-resistant organisms (MRO), as well as
      other pathogens, such as Clostridium difficile. This has resulted in a timely
      focus on a range of HAI prevention actions. Core components include antimicrobial
      stewardship, to reduce overuse and ensure evidence-based antimicrobial use;
      infection prevention strategies, to control MRO - particularly methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp.
      (VRE) and, more recently, multi-resistant Gram-negative bacteria; enhanced
      institutional investment in hand hygiene; hospital cleaning and disinfection; and
      the development of prescribing guidelines and standards of care. AMR surveillance
      and comparisons of prescribing are useful feedback activities once effectively
      communicated to end users. Successful implementation of these strategies requires
      cultural shifts at local hospital level and, to tackle the serious threat posed
      by AMR, greater co-ordination at a national level. HAI prevention needs to be
      multi-modal, requires broad healthcare collaboration, and the strong support and
      accountability of all medical staff.

PMID- 29224206
TI  - Author reply.

PMID- 29224207
TI  - Acute kidney injury is under-recognised and under-reported in hospitalised
      patients in Australia.
AB  - Acute kidney injury (AKI) in hospitalised patients is associated with adverse
      outcomes; however, it remains unrecognised and under-reported. A total of 48 045
      serum creatinine results from 8129 tertiary hospital inpatients were reviewed.
      The prevalence of AKI was 4.33%. Mortality was significantly higher in patients
      with AKI (16.76%) compared to those without AKI (1.88%, P < 0.001). Documentation
      of AKI in discharge summaries was poor.

PMID- 29224208
TI  - Time to resurrect hypertension.

PMID- 29224209
TI  - SIRCLE: a randomised controlled cost comparison of self-administered short-course
      isoniazid and rifapentine for cost-effective latent tuberculosis eradication.
AB  - BACKGROUND: Currently, treatment of latent tuberculosis infection (LTBI) in
      Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month
      course of weekly isoniazid and rifapentine (3HP) has been shown to be as
      effective as 9 months of daily isoniazid, and associated with less
      hepatotoxicity; however, rifapentine is not currently available in Australia.
      Introduction of this regimen would have apparent advantages for people with LTBI
      in Victoria by safely shortening duration of LTBI therapy. However, the cost
      benefit of this new therapeutic approach is uncertain. AIM: Cost-analysis of
      standard and short-course therapy for LTBI in an Australian context. METHODS:
      Single-centre randomised controlled trial conducted between December 2013-March
      2016. Participants underwent 1:1 randomisation to either a 9-month course of
      daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The
      primary outcome measure was total healthcare system costs (in Australian dollars;
      AUD) per completed course of LTBI therapy. Secondary cost analyses were performed
      to consider varying assumptions regarding commercial cost of rifapentine.
      RESULTS: Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in
      the 3HR group completed therapy. One patient in the 3HP group was hospitalised
      for a febrile illness; no hospitalisations were recorded in the 9H group. The
      cost per completed course of 9H was 601 AUD, while that of 3HP was significantly
      lower at 511 AUD (P < 0.01). CONCLUSIONS: This study provides cost analysis
      evidence to support the use of 3HP for the treatment of LTBI in Australia.

PMID- 29224210
TI  - Medical toxicology in the Old Testament. The poisonous pottage.

PMID- 29224211
TI  - Medication reconciliation at two teaching hospitals in Australia: a missed
      opportunity?
AB  - Medication reconciliation prevents medication related harm at patient
      hospitalisation. This cross-sectional study demonstrated that the Hunter New
      England Health Admission Medication History Form that supports the two processes
      is underutilised in two hospitals in New South Wales with many doctors unaware of
      the form and pharmacists facing understaffing and time constraints for completing
      it. Triaging of patients and, more collaboration between doctors and pharmacists
      are required for efficient in-hospital medication reconciliation.

PMID- 29224212
TI  - The utility of FDG-PET in complex neurological conditions.

PMID- 29224213
TI  - The threat among us: significance and scale of diabetic chronic kidney disease in
      Australia.

PMID- 29224214
TI  - Facial swelling and foreign body granulomatous reaction to hyaluronic acid filler
      in the setting of tyrosine kinase inhibitor therapy.

PMID- 29224215
TI  - Deleterious variants in DCHS1 are prevalent in sporadic cases of mitral valve
      prolapse.
AB  - BACKGROUND: A recent study identified DCHS1 as a causal gene for mitral valve
      prolapse. The goal of this study is to investigate the presence and frequency of
      known and novel variants in this gene in 100 asymptomatic patients with moderate
      to severe organic mitral regurgitation. METHODS: DNA sequencing assays were
      developed for two previously identified functional missense variants, namely
      p.R2330C and p.R2513H, and all 21 exons of DCHS1. Pathogenicity of variants was
      evaluated in silico. RESULTS: p.R2330C and p.R2513H were not identified in this
      cohort. Sequencing all coding regions revealed eight missense variants including
      six considered deleterious. This includes one novel variant (p.A2464P) and two
      rare variants (p.R2770Q and p.R2462Q). These variants are predicted to be
      deleterious with combined annotation-dependent depletion (CADD) scores greater
      than 25, which are in the same range as p.R2330C (CADD = 28.0) and p.R2513H (CADD
      = 24.3). More globally, 24 of 100 cases were carriers of at least one in silico
      predicted deleterious missense variant in DCHS1, suggesting that this single gene
      may account for a substantial portion of cases. CONCLUSION: This study reveals an
      important contribution of germline variants in DCHS1 in unrelated patients with
      mitral valve prolapse and supports genetic testing of this gene to screen
      individuals at risk.

PMID- 29224216
TI  - Association of School-Based Physical Activity Opportunities, Socioeconomic
      Status, and Third-Grade Reading.
AB  - BACKGROUND: Socioeconomic status (SES) is the most accurate predictor of academic
      performance in US schools. Third-grade reading is highly predictive of high
      school graduation. Chronic physical activity (PA) is shown to improve cognition
      and academic performance. We hypothesized that school-based PA opportunities
      (recess and physical education) would moderate the negative association between
      SES and third-grade reading. METHODS: Schools serving third-grade students were
      surveyed (N = 1279) for minutes/week of PA opportunities. Allotted weekly PA time
      and achievement data from participating schools (N = 784) were recorded and
      analyzed. To test the moderator hypothesis, moderated multiple regression
      analysis was conducted. RESULTS: The interaction of PA opportunities and SES
      explained a significant increase in variance in third-grade reading (b = .053, p
      < .001), thus moderating the relationship between SES and third-grade reading.
      Further analysis showed that schools offering greater than 225 minutes/week of PA
      opportunities experienced a greater (+5%) moderating effect. CONCLUSION: School
      based PA opportunities positively moderate the relationship between SES and third
      grade reading, and lowest SES schools experience greater moderating effects.
      Future research should consider PA opportunities as a moderator of the SES
      academic achievement relationship, and school policy makers should consider the
      influence that PA opportunities have on student achievement at varying SES
      levels.

PMID- 29224217
TI  - Longitudinal Trajectory of the Relationship Between Self-Esteem and Substance Use
      From Adolescence to Young Adulthood.
AB  - BACKGROUND: We examined the longitudinal trajectory of substance use (binge
      drinking, marijuana use, and cocaine use) in relation to self-esteem from
      adolescence to young adulthood. METHODS: Generalized estimating equation models
      were fit using SAS to investigate changes in the relation between self-esteem and
      each substance use (binge drinking, marijuana use, and cocaine use) from
      adolescence to young adulthood. Data were drawn from the 3 waves of the National
      Longitudinal Study of Adolescent Health, a nationally representative sample of
      middle and high school students in the United States (N = 6504). RESULTS: Self
      esteem was a significant predictor for the use of all 3 substances at 15 years of
      age (ps < .001). However, at age 21, self-esteem no longer predicted binge
      drinking and marijuana use in the controlled model. CONCLUSIONS: It appears that
      self-esteem loses its protective role against substance use except cocaine use as
      adolescents transition to young adulthood.

PMID- 29224218
TI  - Researchers Supporting Schools to Improve Health: Influential Factors and
      Outcomes of Knowledge Brokering in the COMPASS Study.
AB  - BACKGROUND: Although schools are considered opportune settings for youth health
      interventions, a gap between school health research and practice exists. COMPASS,
      a longitudinal study of Ontario and Alberta secondary students and schools (2012
      2021), used integrated knowledge translation to enhance schools' uptake of
      research findings. Schools received annual summaries of their students' health
      behaviors and suggestions for action, and were linked with COMPASS knowledge
      brokers to support them in making changes to improve student health. This
      research examines the factors that influenced schools' participation in knowledge
      brokering and associated outcomes. METHODS: School- and student-level data from
      the first 3 years of the COMPASS study (2012-2013; 2013-2014; 2014-2015) were
      used to examine factors that influenced knowledge brokering participation, school
      level changes, and school-aggregated student health behaviors. RESULTS: Both
      school characteristics and study-related factors influenced schools'
      participation in knowledge brokering. Knowledge brokering participation was
      significantly associated with school-level changes related to healthy eating,
      physical activity, and tobacco programming, but the impact of those changes was
      not evident at the aggregate student level. CONCLUSIONS: Knowledge brokering
      provided a platform for collaboration between researchers and school
      practitioners, and led to school-level changes. These findings can inform future
      researcher-school practitioner partnerships to ultimately enhance student health.

PMID- 29224219
TI  - Measuring School Functioning in Students With Chronic Fatigue Syndrome: A
      Systematic Review.
AB  - BACKGROUND: It is often surmised that school functioning is significantly
      impacted in chronic fatigue syndrome (CFS); however, how this phenomenon
      manifests itself has rarely been characterized. METHODS: This systematic review
      synthesized and critically appraised methods, constructs, and instruments used to
      assess school functioning in students with CFS. Searches were conducted in
      electronic databases (CINAHL, MEDLINE, PubMed, ERIC, and PsycINFO) to locate
      empirical studies that measured school functioning in children and adolescents
      with CFS. RESULTS: A total of 36 papers met the inclusion criteria. By far the
      most commonly reported school functioning construct measured related to school
      attendance. This was followed by academic functioning, achievement motivation,
      and educational services received. Little consistency was found in the
      measurement of these constructs across studies. CONCLUSIONS: The current review
      revealed that the school experiences of children and adolescents with CFS have
      rarely been characterized beyond school absenteeism. Improvements in current
      assessment methods are required to comprehensively understand the impact of CFS
      on school functioning. Completely understanding the multiple aspects of school
      functioning will help to inform targeted strategies to optimize educational
      outcomes for students with CFS.

PMID- 29224220
TI  - Why and How Schools Make Nutrition Education Programs "Work".
AB  - BACKGROUND: There are many potential health benefits to having nutrition
      education programs offered by expert outside sources in schools. However, little
      is known about why and how schools initiate, implement, and institutionalize
      them. Gaining this understanding may allow the impact and reach of nutrition and
      other health education programs in schools to be extended. METHODS: A total of 22
      school community members from 21 purposefully selected New York City public
      elementary schools were interviewed using a semistructured interview protocol
      about their schools' experiences initiating, implementing, and institutionalizing
      nutrition education programs. Interviews were audiotaped and transcribed.
      Chronological narratives were written detailing each school's experience and
      passages highlighting key aspects of each school's experience were identified.
      These passages (N = 266) were sorted into domains and themes which were
      regrouped, resorted, and adjusted until all researchers agreed the domains and
      themes represented the collective experiences of the schools. RESULTS: The
      interviews elicited 4 broad domains of action: building motivation, choosing
      programs, developing capacity, and legitimizing nutrition education. Within each
      domain, themes reflecting specific actions and thoughts emerged. CONCLUSIONS: The
      identified domains of action and their themes highlight specific, practical
      actions that school health advocates can use to initiate, implement, and
      institutionalize nutrition education programs in schools.

PMID- 29224221
TI  - Exploring the Associations Among Nutrition, Science, and Mathematics Knowledge
      for an Integrative, Food-Based Curriculum.
AB  - BACKGROUND: Explore associations between nutrition, science, and mathematics
      knowledge to provide evidence that integrating food/nutrition education in the
      fourth-grade curriculum may support gains in academic knowledge. METHODS:
      Secondary analysis of a quasi-experimental study. Sample included 438 students in
      34 fourth-grade classrooms across North Carolina and Ohio; mean age 10 years old;
      gender (I = 53.2% female; C = 51.6% female). Dependent variable = post-test
      nutrition knowledge; independent variables = baseline-nutrition knowledge, and
      post-test science and mathematics knowledge. Analyses included descriptive
      statistics and multiple linear regression. RESULTS: The hypothesized model
      predicted post-nutrition knowledge (F(437) = 149.4, p < .001; Adjusted R = .51).
      All independent variables were significant predictors with positive association.
      CONCLUSIONS: Science and mathematics knowledge were predictive of nutrition
      knowledge indicating use of an integrative science and mathematics curriculum to
      improve academic knowledge may also simultaneously improve nutrition knowledge
      among fourth-grade students. Teachers can benefit from integration by meeting
      multiple academic standards, efficiently using limited classroom time, and
      increasing nutrition education provided in the classroom.

PMID- 29224222
TI  - Chronic Pain in the School Setting: The Teachers' Point of View.
AB  - BACKGROUND: The aims of this study were to (1) examine the reactions of teachers
      and student teachers to children experiencing pain, (2) identify the most common
      challenges and potential resources that are associated to dealing with them, and
      (3) examine whether their responses differed as a function of their experience or
      sex. METHODS: Forty teachers and 318 student teachers completed a survey which
      included descriptive information, a questionnaire that assesses different
      responses of participants to children who experience pain, and provides a list of
      problems and resources that participants might encounter and implement,
      respectively, when dealing with these children. RESULTS: The study participants
      most often endorsed use of coping and health-promoting responses. Experienced
      teachers endorsed solicitous responses significantly more often than student
      teachers. Women reported responding more with solicitous responses than men.
      Absenteeism and the negative effect of pain on the ability of students to engage
      in school activities were the most common pain-related challenges mentioned by
      the study participants overall. CONCLUSIONS: The findings emphasize (1) the need
      for developing guidelines to help teachers to help students experiencing chronic
      pain, and (2) the importance of including information about pediatric chronic
      pain in teachers training.

PMID- 29224223
TI  - Altering the School Breakfast Environment Reduces Barriers to School Breakfast
      Participation Among Diverse Rural Youth.
AB  - BACKGROUND: The purpose is to determine if altering school breakfast policies and
      the school breakfast environment will positively impact adolescent beliefs of the
      barriers and benefits of eating breakfast. METHODS: There were 904 adolescents
      from 16 rural high schools, Minnesota, in the BreakFAST Study who reported eating
      breakfast fewer than 4 times per week at baseline. Schools were randomized to
      intervention (N = 8 schools) or delayed intervention (N = 8) condition. The
      intervention lasted 1 school year. Students completed an online survey of beliefs
      of barriers and benefits to eating breakfast at baseline and follow-up. Summative
      scales were created. Bivariate and multivariate linear regression, accounting for
      clustering by school, was performed using SAS. Sex interaction was tested. Models
      tested the effect of the intervention on change in summative scales from baseline
      to follow -up. RESULTS: Participants were 54% female, 69.1% white, 36.6% eligible
      for free or reduced-price meals (FRM) and 13.1% of families received public
      assistance. The change in reported barriers was significantly different in
      intervention versus control schools (Net difference = 1.0, p = .03). There was no
      intervention effect of perceived benefits. CONCLUSIONS: A school-based policy and
      environmental change intervention can successfully reduce perceived barriers to
      eating school breakfast.

PMID- 29224224
TI  - Healthy and Ready to Learn: Effects of a School-Based Public Health Insurance
      Outreach Program for Kindergarten-Aged Children.
AB  - BACKGROUND: Rates of child insurance coverage have increased due to expansions in
      public programs, but many eligible children remain uninsured. Uninsured children
      are less likely to receive preventative care, which leads to poorer health and
      achievement in the long term. This study is an evaluation of a school-based
      health insurance outreach initiative, "Healthy and Ready to Learn," aiming to
      identify and enroll uninsured kindergarteners in areas of high economic need in
      16 counties in North Carolina. METHODS: Regression discontinuity design and
      difference-in-differences analyses were used to estimate the effect of the
      initiative on Medicaid and CHIP enrollment (primary outcome) and preventive care
      use (well-child visits; secondary outcome). Focus groups and key-informant
      interviews were conducted to assess best practices and identify barriers to
      outreach for child enrollment. RESULTS: The initiative increased enrollment rates
      by 12.2% points and increased well-child exam rates by 8.6% points in the RD
      models, but not differences-in-differences, and did not significantly increase
      well-child visits. CONCLUSIONS: Findings demonstrate the potential benefits of
      using schools as a point of intervention in enrolling young children in public
      health insurance and as a source of trusted information for low-income parents.

PMID- 29224226
TI  - Bizarre appearance of chronic cutaneous lupus erythematosus of face mimicking
      factitial dermatitis.

PMID- 29224225
TI  - Downregulation of 15-hydroxyprostaglandin dehydrogenase by interleukin-1beta from
      activated macrophages leads to poor prognosis in pancreatic cancer.
AB  - Chronic inflammation has a crucial role in cancer development and the progression
      of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The
      arachidonate cascade is a major inflammatory pathway that produces several
      metabolites, such as prostaglandin E2. The enzyme 15-hydroxyprostaglandin
      dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in
      several types of cancer; however, the molecular mechanisms of 15-PGDH suppression
      are unclear. The current study was carried out to elucidate the molecular
      mechanisms and clinical significance of 15-PGDH suppression in PDAC. Here, we
      showed that interleukin-1beta (IL-1beta), a pro-inflammatory cytokine,
      downregulates 15-PGDH expression in PDAC cells, and that IL-1beta expression was
      inversely correlated with 15-PGDH levels in frozen PDAC tissues. We also found
      that activated macrophages produced IL-1beta and reduced 15-PGDH expression in
      PDAC cells. Furthermore, the number of CD163-positive tumor-associated
      macrophages was shown to be inversely correlated with 15-PGDH levels in PDAC
      cells by immunohistochemical staining of 107 PDAC samples. Finally, we found that
      low 15-PGDH expression was significantly associated with advanced tumors,
      presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC
      patients. Our results indicate that IL-1beta derived from TAMs suppresses 15-PGDH
      expression in PDAC cells, resulting in poor prognosis of PDAC patients.

PMID- 29224227
TI  - Capacity-oriented approaches to developing childhood obesity interventions: a
      systematic review.
AB  - Capacity-oriented approaches to health interventions seek to empower the target
      population or community to manage the health issue themselves using resources
      they can control. Positive deviance, resilience and asset-based approaches are
      three such methods of developing and implementing health interventions. This
      study aimed to review the efficacy of interventions explicitly applying these
      methods in addressing childhood obesity using adiposity as the primary outcome,
      measured by standardized body mass index. The search strategy was developed and
      implemented across four electronic databases. Of the 181 records identified and
      screened, 11 studies were identified as using a capacity-oriented approach
      overall. Asset-based approaches (n = 8 studies) consisted of 47 880 participants,
      positive deviance (n = 2 studies) consisted of 781 participants, and resilience
      based interventions (n = 1 study) consisted of 35 participants. The asset-based
      approaches were mixed, with three of the eight studies showing a significant
      reduction in adiposity, while the other five did not find a difference. The
      positive deviance and resilience-based studies showed signs of efficacy in
      reducing adiposity. There was significant design heterogeneity across studies,
      and varied interpretations and definitions of the approaches were used. Further
      work should attempt to achieve some consensus on the use of these approaches to
      facilitate comparison and advance the science of capacity-oriented interventions
      for childhood obesity.

PMID- 29224229
TI  - Power Doppler ultrasound assessment of vascularization in hidradenitis
      suppurativa lesions.
AB  - BACKGROUND: Ultrasound (US) and Power Doppler (PD) US are useful tools to study
      and monitor the patients with hidradenitis suppurativa (HS). OBJECTIVE: Describe
      the PD signal of HS nodules, abscesses and fistulas. METHODS: A retrospective
      analysis of PD in mild, moderate and severe HS patients, collecting all
      demographic and clinical data. The lesions were classified according to their US
      morphology, describing the vascular degree - high, moderate and minimal - and
      distribution - peripheral, internal and mixed. Statistical analysis was performed
      using odds ratio and bivariate regression. RESULTS: A total of 241 lesions, 62
      nodules, 64 abscesses, 99 simple fistulas and 16 complex fistulas, from 61
      patients with HS, were included. Vascular distribution was defined peripheral in
      143/241, mixed in 55/241 and internal in 0/241 lesions, regardless the clinical
      type. Qualitative Doppler showed high vascularization in 44/241 lesions, moderate
      in 79/241 and minimal in 75/241, despite the clinical type. All lesions showed
      resistive index <0.7. Age, disease's duration, size of the lesions, high
      Sartorius score and high BMI showed positive statistical correlation with both PD
      signal and mixed vascular distribution. No statistical significance was evidenced
      for vascular degree measurements. LIMITATIONS: US cannot detect lesions <0.1 mm.
      CONCLUSION: Vascular distribution of HS lesions can be evaluated by PD with
      additional relevant information for earlier and better disease management.

PMID- 29224228
TI  - Newcastle disease virus co-expressing interleukin 7 and interleukin 15 modified
      tumor cells as a vaccine for cancer immunotherapy.
AB  - Interleukin 15 (IL15) and IL7 are two cytokines essential for T cell development
      and homeostasis. In order to improve the antitumor activity by Newcastle disease
      virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing
      IL15 and IL7 (LX/IL(15+7)) through incorporation of a 2A self-processing peptide
      into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7)
      expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine
      melanoma cells modified with LX/IL(15+7) could significantly enhance the
      antitumor immune response in vitro. Then, the antitumor effects of tumor vaccine
      modified with recombinant virus were tested in the murine tumor models. We
      observed strong antitumor responses induced by LX/IL(15+7)-modified tumor cells
      both in prophylaxis and therapeutic models. Although the tumor-infiltrating CD4+
      T cells and CD8+ T cells were both increased, the antitumor activity of the tumor
      vaccine modified with LX/IL(15+7) was dependent on CD8+ T cells. Taken together,
      our data strongly indicated that tumor vaccine modified with NDV strain
      LX/IL(15+7) is a promising agent for cancer immunotherapy.

PMID- 29224230
TI  - Is neutrophilic desquamative erythroderma a form of acute generalized
      exanthematous pustulosis?

PMID- 29224231
TI  - Ultrastructural aspects of hairs of Chediak-Higashi syndrome.

PMID- 29224232
TI  - Physical activity and family-based obesity treatment: a review of expert
      recommendations on physical activity in youth.
AB  - Targeting physical inactivity in children is pertinent to aiding in the decrease
      of childhood obesity rates. Only 33% of adolescents are obtaining the recommended
      goal of at least 60 min of physical activity per day. The objectives of this
      review are to summarize professional recommendations for physical activity and
      exercise in children and adolescents, and identify family-centred strategies that
      can be implemented by weight management clinicians. Clinically oriented
      recommendations and policy statements from professional organizations were
      identified through literature and internet searches, summarized using rubrics of
      aerobic, muscle strengthening and bone strengthening exercise, then examined for
      details on family-based focus, inclusion of child developmental stage and age,
      and application to the prevention and treatment of obesity. Current
      recommendations give guidelines for the amount of physical activity that children
      should acquire and how many days a week activities should occur. However,
      available guidelines need an improved approach to addressing the role of the
      parents and caregivers in targeting physical activity and weight management in
      youth. Efforts must be taken in order to make sure that the types of physical
      activity offered are both suitable and enjoyable. Sports, games, free play and
      other age appropriate activities are adequate ways to increase moderate to
      vigorous physical activity in children. Differentiating physical activities types
      in accordance with developmental stage, level of enjoyment, and family
      characteristics is needed to establish sustainable habits. One paediatric obesity
      program has developed approaches to teaching families fun and engaging ways to be
      active together.

PMID- 29224233
TI  - Review article: Methodology for the 'rapid review' series on musculoskeletal
      injuries in the emergency department.
AB  - Musculoskeletal injuries are a common presentation to the ED, with significant
      costs involved in the management of these injuries, variances in care within the
      ED and associated morbidity. A series of rapid review papers were completed to
      guide best practice for the assessment and management of common musculoskeletal
      injuries presenting to the ED. This paper presents the methodology used across
      the rapid reviews. PubMed, CINAHL, EMBASE, TRIP and the grey literature,
      including relevant organisational websites, were searched in 2015. The search was
      repeated consistently for each topic area (injuries of the foot and ankle, knee,
      hand and wrist, elbow, shoulder, lumbar spine and cervical spine). English
      language primary studies, systematic reviews and guidelines that were published
      in the last 10 years and addressed acute musculoskeletal injury management were
      considered for inclusion. Data extraction of each included article was conducted,
      followed by a quality appraisal. The extracted data from each article was
      synthesised to group similar evidence together. For each rapid review, the
      evidence has been organised in a way that a clinician can direct their attention
      to a specific component of the clinical cycle of care in the ED, such as the
      assessment, diagnostic tests, management and follow-up considerations from ED.
      The series of rapid reviews are designed to foster evidence-based practice within
      the ED, targeting the injuries most commonly presenting. The reviews provide
      clinicians in EDs with rapid access to the best current evidence, which has been
      synthesised and organised to assist decision-making.

PMID- 29224235
TI  - Long-term cardiovascular reprogramming by short-term perinatal exposure to
      nicotine's main metabolite cotinine.
AB  - AIM: Gather 'proof-of-concept' evidence of the adverse developmental potential of
      cotinine (a seemingly benign biomarker of recent nicotine/tobacco smoke
      exposure). METHODS: Pregnant C57 mice drank nicotine- or cotinine-laced water for
      6 wks from conception (NPRE = 2% saccharin + 100 MUg nicotine/mL; CPRE = 2%
      saccharin + 10 MUg cotinine/mL) or 3 wks after birth (CPOST = 2% saccharin + 30
      MUg cotinine/mL). Controls drank 2% saccharin (CTRL). At 17 +/- 1 weeks (male
      pups; CTRL n = 6; CPOST n = 6; CPRE n = 8; NPRE n = 9), we assessed (i)
      cardiovascular control during sleep; (ii) arterial reactivity ex vivo; and (iii)
      expression of genes involved in arterial constriction/dilation. RESULTS: Blood
      cotinine levels recapitulated those of passive smoker mothers' infants. Pups
      exposed to cotinine exhibited (i) mild bradycardia - hypotension at rest (p <
      0.001); (ii) attenuated (CPRE , p < 0.0001) or reverse (CPOST ; p < 0.0001) BP
      stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein
      kinase C (p < 0.001) and elevated adrenergic receptor mRNA (p < 0.05; all drug
      treated arteries); and (iv) endothelial dysfunction (NPRE only). CONCLUSION:
      Cotinine has subtle, enduring developmental consequences. Some cardiovascular
      effects of nicotine can plausibly arise via conversion into cotinine. Low-level
      exposure to this metabolite may pose unrecognised perinatal risks. Adults must
      avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.

PMID- 29224234
TI  - An observational study of benzodiazepine prescription during inpatient alcohol
      detoxification for patients with vs. without chronic pretreatment with high
      dosage baclofen.
AB  - High-dose baclofen is prescribed as a maintenance treatment to reduce alcohol use
      in patients with alcohol use disorder. Nevertheless, some patients still have
      massive alcohol intakes and require inpatient alcohol withdrawal. To compare the
      oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in
      patients with vs. without steady-state pretreatment with high-dose baclofen.
      Retrospective chart review study. Prescribed benzodiazepine dose expressed in
      diazepam-equivalent was compared between groups. Thirty-one patients were
      assessed in the high-dose maintenance baclofen group and compared to 31 matched
      patients not receiving baclofen. No statistically significant difference was
      evident between groups regarding levels of benzodiazepines prescribed. The mean
      diazepam-equivalent dose during the first 7 days was 294 +/- 149 mg in the
      baclofen group vs. 310 +/- 133 mg (t-test = 0.440, P = 0.661) in matched
      controls. Steady-state high-dose baclofen before an inpatient alcohol cessation
      hospitalization does not lower the needed benzodiazepine dose in the management
      of alcohol withdrawal symptoms.

PMID- 29224236
TI  - Prognostic factors of prostate cancer mortality in a Finnish randomized screening
      trial.
AB  - OBJECTIVES: To identify the prognostic factors of prostate cancer death among
      patients enrolled in a Finnish prostate cancer screening trial. METHODS: Data on
      TNM stage, Gleason score, serum prostate-specific antigen at diagnosis,
      comorbidity and primary treatment were collected from medical records, as well as
      date and cause of death from Statistics Finland. Four prognostic risk groups were
      defined based on TNM stage, Gleason score and prostate-specific antigen at
      diagnosis. Hazard ratios and their 95% confidence intervals for prostate cancer
      death were calculated using Cox regression and competing-risk analysis with
      follow up from randomization. The differences in the effects of prognostic
      factors were assessed using interaction terms. RESULTS: The 15-year survival was
      significantly lower among cases in the control arm compared with the screening
      arm (0.90 vs 0.92). However, the survival advantage was limited to screen
      detected cases (0.94 vs 0.91 in cases detected outside screening). The prognostic
      risk group was the strongest factor predicting survival in the control arm, but
      weaker in screen-detected cases. Advanced disease was associated with
      substantially poorer outcome in cases detected outside screening than in screen
      detected disease. Primary treatment had a similar effect in all groups.
      Comorbidity had a small prognostic effect in the control arm only. CONCLUSIONS:
      Prognostic factors had a different effect on the outcome of cases detected
      through screening as those diagnosed otherwise. A high diagnostic prostate
      specific antigen and advanced disease carried a poor prognosis, especially among
      the cases detected outside screening, even when lead-time was eliminated. This
      shows that the screening resulted in earlier treatment among the cases in the
      screening arm.

PMID- 29224238
TI  - Laparoscopic splenectomy with selective intra-corporeal ligation of splenic hilar
      vessels for high grade splenic injury - video vignette.
AB  - A 59-year-old hemodynamically stable female is admitted following a domestic fall
      with blunt left sided thoraco-abdominal trauma. She lived alone and had multiple
      comorbidities including hepatitis C virus positive splenomegaly, chronic
      psychosis with a history of opioid and alcohol abuse. A CT-scan of thorax and
      abdomen with IV contrast showed left lung contusions and multiple left rib
      fractures with no pneumothorax, a high grade splenic injury with intra
      parenchymal hematoma and small arterial blushes in the superior splenic pole
      associated with celiac trunk stenosis, mild intra-abdominal free fluid and grade
      II injury to the left kidney. This article is protected by copyright. All rights
      reserved.

PMID- 29224237
TI  - Major haemorrhage fatalities in the Australian national coronial database.
AB  - OBJECTIVE: The aim of the study is to describe the epidemiology of major bleeding
      fatalities. METHODS: A case series analysis of Australia's National Coronial
      Information System was conducted. Keywords were used to search for closed cases
      of major haemorrhage in the state of Victoria for the period 1 January 2009 to 31
      December 2011. Coroners' findings, autopsy reports and police reports of cases
      were reviewed. Demographic data were extracted, and cases were assigned to a
      clinical bleeding context. RESULTS: A total of 427 cases of major bleeding
      causing death were identified. The cohort was predominately men (69%), with a
      median age of 63 years (interquartile range 45-77 years). Trauma accounted for
      38%, gastrointestinal haemorrhage 28%, surgical/procedural bleeding 14%,
      ruptured/leaking aneurysms 12% and other 8%. Most events began in homes (46%),
      hospitals (22%) and at the roadside (17%). Of those whose haemorrhage began in
      the community, 69% did not survive to hospital. CONCLUSIONS: Major bleeding
      fatalities occurred across a diverse range of contexts, with trauma and
      gastrointestinal bleeding accounting for most deaths. The majority of patients
      did not survive to reach hospital. Major haemorrhage occurring entirely outside
      hospital may be underrecognised from analyses of datasets based primarily on
      traumatic or in-hospital bleeding. These findings have implications for
      management of pre-hospital resuscitation and development of clinical practice
      guidelines for identification and management of major bleeding in the community.

PMID- 29224239
TI  - Personalized stepwise vascular control during complex hepatectomy involving
      hepatocaval confluence.
AB  - BACKGROUND: This study introduces an innovative stepwise vascular control
      technique to address the high risk of massive bleeding from main hepatic veins
      and the retro-hepatic inferior vena cava during hepatectomy involving hepatocaval
      confluence. METHODS: From January 2010 to July 2016, 80 patients underwent
      stepwise vascular occlusion during complex liver resection involving hepatocaval
      confluence. Relevant clinical data were collected and compared with those
      obtained in parallel studies. The protocol has been registered in the Protocol
      Registration and Results System as protocol NCT02996006. RESULTS: All 80 patients
      underwent portal triad (PT), infra-hepatic inferior vena cava (IIVC) and supra
      hepatic inferior vena cava (SIVC) preparation for occlusion in that order; PT, PT
      + SIVC and PT + IIVC + SIVC occlusions were performed during liver resection for
      six, 42 and 32 patients, respectively. The PT, IIVC and SIVC clamping times were
      12.9 +/- 2.5, 9.1 +/- 2.1 and 5.1 +/- 1.4 min, respectively. The mean blood loss
      was 504.1 +/- 234.5 mL. Sixteen patients received blood transfusions.
      Haemodynamic parameters remained stable. No patients had life-threatening
      complications or died (Clavien-Dindo grade IV or V). Compared with other
      techniques used in parallel studies, this technique has the advantage of
      decreased blood loss in less warm ischaemia time. CONCLUSION: For complex
      hepatectomy involving hepatocaval confluence, this newly described stepwise
      vascular control technique was efficacious and feasible for controlling
      intraoperative bleeding.

PMID- 29224240
TI  - Phototherapy in France: quantitative data (2007-2016) from the National Health
      Insurance Register.

PMID- 29224241
TI  - Cost-effectiveness of bariatric surgery in adolescents with severe obesity in the
      UK.
AB  - Evidence shows that surgery for severe obesity in adults improves health and
      psychological functioning, and is cost-effective. Data on bariatric surgery for
      adolescents with severe obesity are extremely limited, with no evidence on cost
      effectiveness. We evaluated the lifetime cost-effectiveness of bariatric surgery
      compared with no surgery in adolescents with severe obesity from the UK's
      National Health Service perspective. Eighteen adolescents with body mass index
      >=40 kg m-2 who underwent bariatric surgery (laparoscopic Roux en Y Gastric
      Bypass [RYGB] [N = 9], and laparoscopic Sleeve Gastrectomy [SG] [N = 9]) at
      University College London Hospitals between January 2008 and December 2013 were
      included. We used a Markov cohort model to compare the lifetime expected costs
      and quality-adjusted life years (QALYs) between bariatric surgery and no surgery.
      Mean cost of RYGB and SG procedures were L7100 and L7312, respectively. For RYGB
      vs. no surgery, the incremental cost/QALY was L2018 (95% CI L1942 - L2042) for
      males and L2005 (95% CI L1974 - L2031) for females. For SG vs. no surgery, the
      incremental cost/QALY was L1978 (95% CI L1954 - L2002) for males and L1941 (95%
      CI L1915 - L1969) for females. Bariatric surgery in adolescents with severe
      obesity is cost-effective; it is more costly than no surgery however it markedly
      improved quality of life.

PMID- 29224242
TI  - Dermoscopic observations in disseminated cryptococcosis with cutaneous
      involvement.

PMID- 29224243
TI  - Discovery of a novel thermostable Zn2+ -dependent alcohol dehydrogenase from
      Chloroflexus aurantiacus through conserved domains mining.
AB  - AIMS: The purpose of the study was to demonstrate feasibility of the Conserved
      Domains Database (CDD) for identification of novel biocatalysts with desirable
      properties from a class of well-characterized biocatalysts. METHODS AND RESULTS:
      The thermostable ADH from Sulfolobus solfataricus with a broad substrate range
      was applied as a template for the search for novel thermostable ADHs via CDD.
      From the resulting hits, a putative ADH gene from the thermophilic organism
      Chloroflexus aurantiacus was cloned and expressed in Escherichia coli. The
      resulting enzyme was purified and characterized. With a temperature activity
      optimum of 70 degrees C and a broad substrate spectrum especially for diketones,
      a versatile new biocatalyst was obtained. CONCLUSIONS: Database-based mining in
      CDD is a suitable approach to obtain novel biocatalysts with desirable
      properties. Thereby, the available diversity of similar but not equal enzymes
      within this class can be increased. SIGNIFICANCE AND IMPACT OF THE STUDY: For
      industrial applications, there is a demand for larger diversity of similar well
      characterized enzymes in order to test them for a given process (biodiversity
      screening). For fundamental science, the comparison of enzymes with similar
      function but different sequence can provide insight into structure function
      relationships or the evolution of enzymes. This study gives a good example on how
      this demand can be efficiently met.

PMID- 29224244
TI  - A histopathological classification system of Tyr::NRASQ61K murine melanocytic
      lesions: A reproducible simplified classification.
AB  - Genetically engineered mouse models offer essential opportunities to investigate
      the mechanisms of initiation and progression in melanoma. Here, we report a new
      simplified histopathology classification of mouse melanocytic lesions in
      Tyr::NRASQ61K derived models, using an interactive decision tree that produces
      homogeneous categories. Reproducibility for this classification system was
      evaluated on a panel of representative cases of murine melanocytic lesions by
      pathologists and basic scientists. Reproducibility, measured as inter-rater
      agreement between evaluators using a modified Fleiss' kappa statistic, revealed a
      very good agreement between observers. Should this new simplified classification
      be adopted, it would create a robust system of communication between researchers
      in the field of mouse melanoma models.

PMID- 29224245
TI  - Regulation of c-MYC transcriptional activity by transforming growth factor-beta 1
      stimulated clone 22.
AB  - c-MYC stimulates cell proliferation through the suppression of cyclin-dependent
      kinase (CDK) inhibitors including P15 (CDKN2B) and P21 (CDKN1A). It also
      activates E-box-mediated transcription of various target genes including
      telomerase reverse transcriptase (TERT) that is involved in cellular immortality
      and tumorigenesis. Transforming growth factor-beta 1 (TGF-beta1)-stimulated clone
      22 (TSC-22/TSC22D1) encodes a highly conserved leucine zipper protein that is
      induced by various stimuli, including TGF-beta. TSC-22 inhibits cell growth in
      mammalian cells and in Xenopus embryos. However, underlying mechanisms of growth
      inhibition by TSC-22 remain unclear. Here, we show that TSC-22 physically
      interacts with c-MYC to inhibit the recruitment of c-MYC on the P15 (CDKN2B) and
      P21 (CDKN1A) promoters, effectively inhibiting c-MYC-mediated suppression of P15
      (CDKN2B) and also P21 (CDKN1A) promoter activities. In contrast, TSC-22 enhances
      c-MYC-mediated activation of the TERT promoter. Additionally, the expression of
      TSC-22 in embryonic stem cells inhibits cell growth without affecting its
      pluripotency-related gene expression. These results indicate that TSC-22
      differentially regulates c-MYC-mediated transcriptional activity to regulate cell
      proliferation.

PMID- 29224247
TI  - Cortisol and blood pressure levels decreased in fathers during the first hour of
      skin-to-skin contact with their premature babies.
AB  - AIM: Premature birth is an extremely stressful experience. In 2013 to 2014, we
      explored the physiological stress responses of fathers during their first skin-to
      skin contact (SSC) with their new baby. METHODS: We recruited 49 fathers whose
      partners had given birth to a premature baby of up to 33 weeks and three days.
      The study, in the neonatal intensive care unit (NICU) of a Quebec hospital,
      measured the physiological stress responses of the fathers before and after they
      first experienced SSC with their new baby. Cortisol levels and blood pressure
      were measured, and a generalised estimating equation was used for the data
      analysis. RESULTS: The fathers' cortisol levels decreased from 10.55 nmol/L, with
      a 95% confidence interval (95% CI) of 9.61-11.59 at the beginning of the
      experiment to 8.26 nmol/L (95% CI: 7.51-9.07) after 75 minutes. Meanwhile, their
      systolic blood pressure decreased from 135.16 mmHg (95% CI: 130-140) to 125.25
      mmHg (95% CI: 121-129). CONCLUSION: Fathers who held their baby in SSC for the
      first time showed a significant reduction in physiological stress responses. Our
      findings support hospital practices that enable fathers to experience their first
      intimate contact with their newborn infant in the NICU.

PMID- 29224248
TI  - Is there a pathogenetic link between frontal fibrosing alopecia, androgenetic
      alopecia and fibrosing alopecia in a pattern distribution?

PMID- 29224246
TI  - Circadian peak dopaminergic activity response at the biological clock pacemaker
      (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high
      fat diet.
AB  - Among vertebrate species of the major vertebrate classes in the wild, a seasonal
      rhythm of whole body fuel metabolism, oscillating from a lean to obese condition,
      is a common biological phenomenon. This annual cycle is driven in part by annual
      changes in the circadian dopaminergic signalling at the suprachiasmatic nuclei
      (SCN), with diminution of circadian peak dopaminergic activity at the SCN
      facilitating development of the seasonal obese insulin-resistant condition. The
      present study investigated whether such an ancient circadian dopamine-SCN
      activity system for expression of the seasonal obese, insulin-resistant phenotype
      may be operative in animals made obese amd insulin resistant by high-fat feeding
      and, if so, whether reinstatement of the circadian dopaminergic peak at the SCN
      would be sufficient to reverse the adverse metabolic impact of the high-fat diet
      without any alteration of caloric intake. First, we identified the
      supramammillary nucleus as a novel site providing the majority of dopaminergic
      neuronal input to the SCN. We further identified dopamine D2 receptors within the
      peri-SCN region as being functional in mediating SCN responsiveness to local
      dopamine. In lean, insulin-sensitive rats, the peak in the circadian rhythm of
      dopamine release at the peri-SCN coincided with the daily peak in SCN
      electrophysiological responsiveness to local dopamine administration. However, in
      rats made obese and insulin resistant by high-fat diet (HFD) feeding, these
      coincident circadian peak activities were both markedly attenuated or abolished.
      Reinstatement of the circadian peak in dopamine level at the peri-SCN by its
      appropriate circadian-timed daily microinjection to this area (but not outside
      this circadian time-interval) abrogated the obese, insulin-resistant condition
      without altering the consumption of the HFD. These findings suggest that the
      circadian peak of dopaminergic activity at the peri-SCN/SCN is a key modulator of
      metabolism and the responsiveness to adverse metabolic consequences of HFD
      consumption.

PMID- 29224249
TI  - Pili annulati in a case of Rothmund-Thomson syndrome with a novel frameshift
      mutation in RECQL4.

PMID- 29224251
TI  - Efficacy and safety of fesoterodine treatment for overactive bladder symptoms in
      elderly women with and without hypertension.
AB  - OBJECTIVE: To assess fesoterodine treatment in elderly women with overactive
      bladder with and without hypertension. METHODS: Data for 2527 elderly women with
      overactive bladder symptoms, including urgency urinary incontinence, were pooled
      from 10 double-blind, placebo-controlled fesoterodine studies. RESULTS: A total
      of 1523 elderly women (60.3%) had a history of hypertension, and 1004 women
      (39.7%) had no hypertension history. Overactive bladder symptoms, mean bodyweight
      and mean body mass index at baseline were significantly higher in women with
      overactive bladder and hypertension versus those without hypertension (P < 0.05).
      Statistically significant improvements in overactive bladder symptoms at week 12
      were observed for fesoterodine treatment versus placebo in women with
      hypertension and those without (P < 0.05). The diary-dry rate (no urgency urinary
      incontinence episodes), the proportion with less than eight micturitions/24 h,
      overactive bladder symptom bother and health-related quality of life were also
      statistically significantly improved by fesoterodine treatment in both
      populations. Incidence of treatment-related adverse events with fesoterodine was
      similar in women with hypertension (39.3%) and without hypertension (44.6%). Dry
      mouth and constipation were the most common treatment-related adverse events with
      fesoterodine in women with hypertension (26.2% and 5.2%, respectively) and
      without hypertension (30.5% and 8.0%). CONCLUSIONS: A relationship among the
      severity of overactive bladder symptoms, hypertension and obesity in elderly
      women is suggested. Fesoterodine provides significantly greater improvements in
      overactive bladder symptoms and health-related quality of life versus placebo in
      women with or without hypertension. Hypertension does not appear to affect the
      efficacy and safety of fesoterodine in elderly women with overactive bladder
      symptoms, including urgency urinary incontinence.

PMID- 29224250
TI  - Multiple Autologous Bone Marrow-Derived CD271+ Mesenchymal Stem Cell
      Transplantation Overcomes Drug-Resistant Epilepsy in Children.
AB  - There is a need among patients suffering from drug-resistant epilepsy (DRE) for
      more efficient and less toxic treatments. The objective of the present study was
      to assess the safety, feasibility, and potential efficacy of autologous bone
      marrow cell transplantation in pediatric patients with DRE. Two females and two
      males (11 months to 6 years) were enrolled and underwent a combined therapy
      consisting of autologous bone marrow nucleated cells (BMNCs) transplantation
      (intrathecal: 0.5 * 109 ; intravenous: 0.38 * 109 -1.72 * 109 ) followed by four
      rounds of intrathecal bone marrow mesenchymal stem cells (BMMSCs) transplantation
      (18.5 * 106 -40 * 106 ) every 3 months. The BMMSCs used were a unique population
      derived from CD271-positive cells. The neurological evaluation included magnetic
      resonance imaging, electroencephalography (EEG), and cognitive development
      assessment. The characteristics of BMMSCs were evaluated. Four intravenous and 20
      intrathecal transplantations into the cerebrospinal fluid were performed. There
      were no adverse events, and the therapy was safe and feasible over 2 years of
      follow-up. The therapy resulted in neurological and cognitive improvement in all
      patients, including a reduction in the number of epileptic seizures (from 10 per
      day to 1 per week) and an absence of status epilepticus episodes (from 4 per week
      to 0 per week). The number of discharges on the EEG evaluation was decreased, and
      cognitive improvement was noted with respect to reactions to light and sound,
      emotions, and motor function. An analysis of the BMMSCs' characteristics revealed
      the expression of neurotrophic, proangiogenic, and tissue remodeling factors, and
      the immunomodulatory potential. Our results demonstrate the safety and
      feasibility of BMNCs and BMMSCs transplantations and the considerable
      neurological and cognitive improvement in children with DRE. Stem Cells
      Translational Medicine 2018;7:20-33.

PMID- 29224252
TI  - Are inhaled steroids safe and effective for prevention or treatment of
      bronchopulmonary dysplasia?

PMID- 29224254
TI  - Appendicitis diagnosed on positron emission tomography scan: an 'incidentalitis'.

PMID- 29224253
TI  - Phytochemical Composition and Biological Activities of Dyssodia tagetiflora Lag.
AB  - While plants of the genus Dyssodia are used by man to a certain extent, few
      phytochemical and pharmacological studies have been performed with species of
      this genus. D. tagetiflora is an endemic plant of Mexico and has been used as
      fodder. The aim of this research was to isolate and identify the main bioactive
      components and evaluate the insecticidal, antioxidant, genotoxic and
      cytoprotective activities of D. tagetiflora. The isolated substances included an
      essential oil composed of six monoterpenes, and extracts containing two
      flavonols, three flavonol-glycosides and four thiophenes. The compounds were
      characterized using spectroscopic and spectrometric methods, including GC/MS, MS
      and NMR. The essential oil showed insecticidal activity against Drosophila
      melanogaster larvae. The methanolic extract of D. tagetiflora (DTME) had strong
      antioxidant activity against DPPH and ABTS radicals; DTME showed no evidence of
      genotoxic or cytotoxic effects. In contrast, DTME showed a cytoprotective effect
      attenuating the formation of H2 O2 -induced micronuclei in Vicia faba roots. This
      report is the first to describe the phytochemical and biological activity of D.
      tagetiflora.

PMID- 29224255
TI  - The highest mortality rates in childhood dilated cardiomyopathy occur during the
      first year after diagnosis.
AB  - AIM: The aim of the study was to assess the incidence, mortality and morbidity of
      dilated cardiomyopathy (DCM) and noncompaction of the left ventricle (LVNC) in
      Swedish children. METHODS: We reviewed hospital records of all children with
      dilated cardiomyopathy (DCM) or left ventricular noncompaction cardiomyopathy
      (LVNC) up to the age of 18 in the healthcare region of western Sweden from 1991
      to 2015. RESULTS: In total, 69 cases (61% males) were identified. The combined
      incidence of DCM and LVNC was 0.77 (95% CI 0.59-0.96) per 100 000 person years.
      Children were divided into six groups, and their outcomes were analysed depending
      on their aetiology. Idiopathic DCM was reported in 43%, and familial dilated and
      left ventricular noncompaction aetiology was present in 32%. DCM due to various
      diseases occurred in 8%. DCM associated with neuromuscular diseases was present
      in 16%. The overall risk of death or receiving transplants in children with
      idiopathic and familial DCM was 30% over the study period, and 21% died in the
      first year after diagnosis. CONCLUSION: The combined incidence of DCM and LVNC
      was similar to previous reports. Most children with idiopathic DCM presented
      during infancy, and mortality was highest during the first year after diagnosis.

PMID- 29224256
TI  - Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with
      Myxomatous Mitral Valve Disease.
AB  - BACKGROUND: Right ventricular (RV) dysfunction independently predicts outcomes in
      human myxomatous mitral valve disease (MMVD). There is limited information
      regarding RV systolic function in dogs with MMVD. HYPOTHESIS: Right ventricular
      systolic function differs among stages of disease, decreasing in decompensated
      MMVD. ANIMALS: Thirty-sixclient-owned dogs with MMVD not receiving oral
      cardiovascular medications. METHODS: Prospective clinical study. Dogs were
      categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven
      echocardiographic indices of RV systolic function were measured. Groups were
      compared by 1-way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac
      remodeling falling outside previously established reference intervals were
      compared using Fisher's exact test. Intra- and interobserver measurement
      variability was calculated for each RV function index. RESULTS: The indices TAPSE
      (P = 0.029), RV StL (P = 0.012), and RV StRL (P = 0.041) were significantly
      different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE
      values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs
      (P = 0.027). Measurement variability of TAPSE, RV S', and RV StG was clinically
      acceptable. CONCLUSIONS AND CLINICAL IMPORTANCE: Right ventricular systolic
      function differs between stages of MMVD, increasing in stage B2, and declining in
      stage C. The prognostic importance of RV function indices, particularly TAPSE,
      might be worth evaluating in dogs with MMVD.

PMID- 29224258
TI  - Progressive osseous heteroplasia in a Chinese infant and a novel mutation in the
      GNAS gene.

PMID- 29224257
TI  - Models of care for non-invasive ventilation in the Acute COPD Comparison of three
      Tertiary hospitals (ACT3) study.
AB  - BACKGROUND AND OBJECTIVE: Non-invasive ventilation (NIV) improves clinical
      outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal
      model of care remains unknown. METHODS: We conducted a prospective observational
      non-inferiority study comparing three models of NIV care: general ward (Ward)
      (1:4 nurse to patient ratio, thrice weekly consultant ward round), a high
      dependency unit (HDU) (1:2 ratio, twice daily ward round) and an intensive care
      unit (ICU) (1:1 ratio, twice daily ward round) model in three similar teaching
      tertiary hospitals. Changes in arterial blood gases (ABG) and clinical outcomes
      were compared and corrected for differences in AECOPD severity (Blood urea > 9
      mmol/L, Altered mental status (Glasgow coma scale (GCS) < 14), Pulse > 109 bpm,
      age > 65 (BAP-65)) and co-morbidities. An economic analysis was also undertaken.
      RESULTS: There was no significant difference in age (70 +/- 10 years), forced
      expiratory volume in 1 s (FEV1 ) (0.84 +/- 0.35 L), initial pH (7.29 +/- 0.08),
      partial pressure of CO2 in arterial blood (PaCO2 ) (72 +/- 22 mm Hg) or BAP-65
      scores (2.9 +/- 1.01) across the three models. The Ward achieved an increase in
      pH (0.12 +/- 0.07) and a decrease in PaCO2 (12 +/- 18 mm Hg) that was equivalent
      to HDU and ICU. However, the Ward treated more patients (38 vs 28 vs 15, P <
      0.001), for a longer duration in the first 24 h (12.3 +/- 4.8 vs 7.9 +/- 4.1 vs
      8.4 +/- 5.3 h, P < 0.05) and was more cost-effective per treatment day ($AUD 1231
      +/- 382 vs 1745 +/- 2673 vs 2386 +/- 1120, P < 0.05) than HDU and ICU. ICU had a
      longer hospital stay (9 +/- 11 vs 7 +/- 7 vs 13 +/- 28 days, P < 0.002) compared
      with the Ward and HDU. There was no significant difference in intubation rate or
      survival. CONCLUSION: In acute hypercapnic Chronic obstructive pulmonary disease
      (COPD) patients, the Ward model of NIV care achieved equivalent clinical
      outcomes, whilst being more cost-effective than HDU or ICU models.

PMID- 29224259
TI  - [Expert consensus of precise diagnosis and treatment for pancreatic head cancer
      using three-dimensional visualization technology].
AB  - Three-dimensional (3D) visualization technology in pancreatic head cancers could
      offer decision-making support to preoperative diagnosis, resectability assessment
      and individualized surgical planning. In addition, the pancreas 3D printing helps
      to realize the leapfrog development from 3D images to 3D physical models and
      provides better guidance of the precise surgery of complicated cancers of the
      pancreatic head. In order to standardize the application of 3D visualization and
      3D printing technology in the diagnosis and treatment of pancreatic head cancer,
      Chinese experts in relevant fields were organized by four committees to formulate
      this expert consensus. This consensus give the suggestion from ten aspects on the
      treatment of pancreatic head cancer, such as the preoperative evaluation,
      acquisition method of CT data, the construction of three-dimensional
      visualization model, clinical classification of resectability assessment based on
      the 3D visualization technology, simulation surgery, 3D printing, the guidance
      with 3D visualization technology on pancreatic cancer surgery, intraoperative
      examination of resectability assessment, and the other treatment based on 3D
      visualization technology with pancreatic head cancer. The consensus will give the
      reference to the doctors who is developing or is going to develop the 3D
      visualization technology on pancreatic head cancer.

PMID- 29224260
TI  - [Ten years retrospective review of the application of digital medical technology
      in general surgery in China].
AB  - Digital medical technology is a powerful tool which has forcefully promoted the
      development of general surgery in China. In this article, we reviews the
      application status of three-dimensional visualization and three-dimensional
      printing technology in general surgery, introduces the development situation of
      surgical navigation guided by optical and electromagnetic technology and
      preliminary attempt to combined with mixed reality applied to complicated
      hepatectomy, looks ahead the development direction of digital medicine in the era
      of artificial intelligence and big data on behalf of surgical robot and
      radiomics. Surgeons should proactively master these advanced techniques and
      accelerate the innovative development of general surgery in China.

PMID- 29224261
TI  - [Current situation and prospect of diagnosis and treatment of tuberous sclerosis
      related renal angiomyolipoma].
AB  - Tuberous sclerosis complex is an autosomal dominant disease involving multiple
      organs and multiple systems. The main manifestation is renal angiomyolipoma in
      the kidney. It is the most common cause of death in adults, because of its high
      incidence, rapid growth and bleeding. The incidence of this disease is low and
      the cognition is not enough, so the diagnosis and treatment are lack of
      standardization. Recently, the expert consensus of the diagnosis and treatment of
      tuberous sclerosis related renal angiomyolipoma has been established in China.
      This content fills the gap in this field in China. With the development of
      precision medicine, the diagnosis and treatment of such diseases are also
      progressing.

PMID- 29224262
TI  - [Discussion of N staging category of the eighth edition of The AJCC Esophageal
      Cancer Staging System].
AB  - AJCC Esophageal Cancer Staging System, 8(th) edition will be implemented on
      January 1, 2018. The N staging in 8(th) edition of staging system remains
      following 7(th) edition based on the number of metastatic nodes, except the
      limited revision of the regional lymph node map. N staging revision was reviewed
      from the simple definition of negative (N0) and positive (N1) lymph node(s) to
      the positive node number based proposal (7(th) edition). The 7(th) edition
      staging system, especially the N staging, were proved with more advantages on
      distinguishing disease progression and predicting prognosis of the esophageal
      cancer. On other hand, the disadvantages of 7(th) edition N staging are
      discussed. The refined N staging based on the number of metastatic node station
      is introduced. The extent and station of metastatic node could better reflect the
      disease progression and prognosis according to our research. The controversy on N
      staging of esophagogastric junction cancer is discussed as well. Other reported N
      staging associated index including lymph node ratio, lymphatic vessel invasion
      and biomarkers are reviewed and evaluated.

PMID- 29224263
TI  - [Strategies for the prevention and control of bleeding due to vascular injury in
      thoracoscopic lung surgery].
AB  - The technique of thoracoscopic lung surgery has gradually matured. Nowadays,
      thoracoscope is recommended as the most preferred approach for surgical treatment
      of early stage non-small cell lung cancer in different guidelines. However, there
      are still some cases of accidential major bleeding due to vascular injury during
      thoracoscopic lung surgery. The wall of the hilum vessels is relatively thin.
      These vessels often involve a great portion of the cardiac output blood flow.
      Once the injury happened, the emergent condition may be life-threatening due to
      massive blood loss. Therefore, this became an important factor which hindered the
      development of thoracoscopic lung surgery. In this review, details of the
      vascular injury in thoracoscopic lung surgery were summarized, including the
      incidence of vascular injury, commonly injured sites and reasons of the injuries.
      Among all the cases of thoracoscopic major pulmonary resection, 2.9% to 9.2% may
      suffer from vascular injury during the operation. The most commonly injuried
      sites are pulmonary artery and the branches, and this is also the most critical
      situation during thoracoscopic lung surgery. Hilum adhesion is the most important
      risk factor for vascular injury. On the one hand, the suction-compressing
      angiorrhaphy technique was developed for bleeding control and angioplasty. On the
      other hand, the strategies like pre-control of the pulmonary, cut the bronchus in
      advance, and fire the bronchus and pulmonary artery together may decrease the
      incidence of vascular injury in patients with risk factors.

PMID- 29224264
TI  - [Comparison of the prognostic value of the seventh and eighth edition of The AJCC
      Esophageal Cancer Staging System for the patients with stage II and IIIesophageal
      squamous cell carcinoma].
AB  - Objective: To compare and evaluate the prognostic value of the 7(th) and 8(th)
      edition of The AJCC Esophageal Cancer Staging System for patients with stage II
      and III esophageal squamous cell carcinoma. Methods: The clinical data of 328
      esophageal cancer patients who received operation at Department of Esophageal
      Cancer, Tianjin Tumour Hospital from January 2006 to December 2010 were
      restrospectively analyzed. There were 63 female and 265 male patients. The mean
      age was 65 (range: 33 to 87) years. Univariate and multivariate analysis were
      performed to identify the prognosis factors. Results: The five years overall
      survival rates among patients with stage II and III were both significantly
      different (chi(2)=87.035, 84.730, all P=0.000) according to the 7(th) and 8(th)
      editions of the TNM staging systems. The five years overall survival rate among
      patients with stage IIB and IIIA were significantly different (39.6% vs 23.4%,
      P=0.001) according to the 7(th) edition of the esophageal cancer staging
      systems.According to the 8(th) edition of the esophageal cancer staging system,
      the 5 years survival rate of patients with stage IIA and IIB, IIIB and IV was
      statistically significant (58.5% vs. 35.5%, P=0.040; 18.9% vs. 0, P=0.000). In
      multivariate analysis, tumor size, T staging, N staging and tumor differentiation
      (HR=1.592, 95%CI: 1.185 to 2.139, P=0.002; HR=1.519, 95% CI: 1.236 to 1.867,
      P=0.000; HR=1.647, 95% CI: 1.448 to 1.874, P=0.000; HR=1.404, 95% CI: 1.059 to
      1.861, P=0.018) were the main independent prognosis factors affecting the
      prognosis of esophageal squamous cell carcinoma patients. Conclusions: Both the
      7(th) and the 8(th) editions of TNM staging systems are able to reflect the
      clinical prognosis of patients receiving radical resection of esophageal cancer,
      and the factors of tumor size, differentiaton, invasion depth and lymph node
      metastases are the independent predictors of prognosis. The 8(th) edition
      provides a more detailed and more reasonable for the staging of stage II and III
      for esophageal cancer patients than the 7(th) edition, and it is more accurate
      for the prognosis of patients with esophageal cancer after surgery.

PMID- 29224265
TI  - [Analysis on the clinical therapeutic effects of arterial first approach
      pancreatoduodenectomy in the treatment of borderline resectable pancreatic
      adenocarcinoma].
AB  - Objective: To compare the clinical therapeutic effects of arterial first approach
      pancreaticoduodenectomy(AFA-PD) with standard approach
      pancreaticoduodenectomy(SPD) in the treatment of borderline resectable pancreatic
      cancer (BRPC). Methods: A retrospective analysis of the clinical data of 113
      cases of pancreatic cancer patients from January 2014 to August 2015 at
      Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital, the Second
      Military Medical University, including 43 cases in AFA-PD group and 70 cases in
      SPD group.Every patient had gone high-resolusion computed tomography before the
      surgery, when BRPC was definitely diagnosed by both experienced radiologist and
      pancreatic surgeon.There were 24 males and 19 females in the AFA-PD group, with
      average age of (61.6+/-10.2)years.And in the SPD group, there were 47 males and
      23 females, with average age of (62.7+/-9.4)years. Results: The operation time
      was (210.7+/-31.5)minutes in AFA-PD group, (187.9+/-27.4)minutes in SPD group,
      and peroperative bleeding volume was (1 007.1+/-566.3)ml in AFA-PD group,
      (700.0+/-390.0)ml in the other group.Those two indicators of AFA-PD group,
      compared with SPD group, were relatively higher, the difference was statistically
      significant(all P<0.01). And with regard to postoperative diarrhea(9.3% vs.5.7%),
      postoperative 1, 3 days of white blood cells(postoperative 1 day: (13.3+/
      1.1)*10(9)/L vs.(12.4+/-2.4)*10(9)/L; postoperative 3 days: (12.7+/-1.6)*10(9)/L
      vs.(11.7+/-2.5)*10(9)/L), postoperative 1, 3, 5 days of peritoneal drainage fluid
      volume(postoperative 1 day: (184+/-42)ml vs.(156+/-54)ml; postoperative 3 days:
      (155+/-48)ml vs.(133+/-35)ml; postoperative 5 days: (66+/-20)ml vs.(47+/-31)ml),
      the differences between the two groups were statistically significant (all
      P<0.05). One patient in the SPD group was treated with unplanned secondary
      surgery for postoperative intraperitoneal hemorrhage, and the patient was cured
      and discharged.There was no death in the two groups within 30 days after surgical
      operation and no patient with positive gastric margin, duodenal margin, or
      anterior margin.The resection rate of superiormesenteric artery(SMA) margin R0 in
      AFA-PD group was higher than that in SPD group (P=0.019). The two groups were
      followed up for 14 to 30 months.As for AFA-PD group, the average survival time,
      progression free survival time and median survival time was respectively (20.4+/
      1.2)months, (21.5+/-1.4)months and 20 months.There were 3 cases(7.0%) with local
      recurrence and 8 cases(18.6%) with liver metastasis or distant metastasis.In the
      SPD group, the average survival time, progression free survival time and median
      survival time was (17.1+/-1.1)months, (16.4+/-1.3)months and 16 months,
      respectively.There were 13 cases(18.6%) with local recurrence and 25 cases(35.7%)
      with liver metastasis or distant metastasis.As a result, the AFA-PD group had
      longer survival time(P=0.001)and progression free survival time(P=0.002).
      However, the lower local recurrence and distant metastasis rate in AFA-PD group
      did not reach statistical standard (P>0.05). Conclusion: The arterial first
      approach pancreaticoduodenectomy is safe and effective in the treatment of
      borderline resectable pancreatic cancer, which can improve the resection rate of
      SMA margin R0, and prolong patient survival time.

PMID- 29224266
TI  - [Application of liver three-dimensional visualization technologies in the
      treatment planning of hepatic malignant tumor].
AB  - Objective: To discuss the application of three dimentional(3D)visualization
      technologies in treatment plan of hepatic malignant tumor. Methods: The clinical
      data of 300 patients with liver malignant tumor who received treatment from
      January 2016 to January 2017 in the Third Department of Hepatic Surgery of
      Eastern Hepatobiliary Surgery Hospital was retrospectively analyzed in this
      study, including 221 male and 79 female patients aged from 7 to 76 years with
      median age of 54 years. The median height was 168 cm (115-183 cm), the median
      weight was 65 kg (20-105 kg) and the median tumor volume was 142 ml (23-2 493
      ml). Three-dimensional visualization technology was used in all patients to
      reconstruct liver three-dimensional graphics. Also, two and three-dimensional
      methods were taken respectively to evaluate patients and develop treatment
      strategy. The change of treatment strategy caused by 3D evaluation, actual
      surgical plan, operation time, time of hepatic vascular occlusion, intraoperative
      blood loss, volumes of blood transfusion and postoperative complications was
      observed. Results: After three-dimensional visualization technology was applied,
      75(25%) of 300 patients' treatment strategies had been changed. The range of
      hepatectomy was extended in 25 patients. And 7 of them were due to hepatic venous
      variation, which resulted in increasing drainage area. In other 4 patients, liver
      resections were extended due to lack of perfusion of the liver parenchyma after
      the removal of portal vein. And hepatectomy was expanded in 14 patients in order
      to increase the surgical margin. The range of hepatectomy was reduced in 8
      patients, 4 of which were due to hepatic venous variation, such as hepatic vein
      of segment 4 or lower right posterior hepatic vein. The remaining 4 cases were
      because of insufficient residual liver volume.The surgical resection was
      performed in 278 cases, 257 of which received operation directly. Left
      hepatectomy was performed in 24 patients and right hepatectomy was performed in
      33 patients. Left trisectionectomy was carried out in 12 patients and right
      trisectionectomy was carried out in 11 patients. Caudate lobectomy was applied in
      10 patients. There were 18 cases of left lateral sectionectomy, 7 cases of right
      anterior sectionectomy, 25 cases of right posterior sectionectomy and 18 cases of
      mesohepatectomy. Single or multi segment resection was performed in 99 patients.
      The treatment strategy of thirty-six patients was converted to staged hepatectomy
      (ALPPS 11 cases and portal vein embolization 25 cases). The median operation time
      was 130 minutes (90-360 minutes) and the median inflow blood occlusion time was
      20 minutes (0-75 minutes). Median blood loss volume was 200 ml (20-1 600 ml).
      Thirty-seven of 278 patients received transfusions, and the average red blood
      transfusion volume was (4.4+/-1.7)units (0-8 units). Median hepatic resection
      volume was 530 ml(30-2 600 ml). There were 117 cases of pleural effusion after
      operation, including 3 patients needing invasive therapy. Ascites occurred in 23
      patients, 6 of whom needed invasive therapy. Biliary leakage was observed in 30
      patients. Eight patients occurred hepatic cutting surface hemorrhage, 6 of whom
      received blood transfusion, and 4 of whom underwent laparotomy to stop bleeding.
      Three patients had pulmonary infection after surgery and 3 patients appeared
      biliary obstruction. Deep vein thrombosis took place in 2 patients and portal
      vein thrombosis was observed in 4 patients. No postoperative liver failure and
      death ever happened in our study group. Conclusion: Three-dimensional
      visualization technique can optimize the treatment strategy of patients with
      liver malignant tumor, improve surgical safety.

PMID- 29224267
TI  - [Clinical outcomes of cervical disc herniation treated by posterior percutaneous
      endoscopic cervical discectomy].
AB  - Objective: To evaluate the clinical outcomes of posterior percutaneous endoscopic
      cervical discectomy (PPECD) for cervical disc herniation. Methods: A total of 23
      patients who underwent PPECD for cervical disc herniation at Department of Spine
      Surgery, Guangdong Provincial Hospital of Chinese Medicine from August 2014 to
      April 2016 were reviewed. The mean age of the 17 males and 6 females was 49.5
      years (range from 31 to 61 years). All patients had unilateral upper limb
      radiating symptoms, 13 patients with right upper limb radiating pain and 10
      patients with left upper limb radiation pain, 17 patients with neck pain
      symptoms. Responsible segment: left C(4-5) 1 case, right C(4-5) 2 cases, left C(5
      6) 4 cases, right C(5-6) 8 cases, left C(6-7) 5 cases, right C(6-7) 3
      example.Operating time, length of hospitalization, complications, neck and arm
      Visual analog scale(VAS), and Neck Disability Index(NDI) were evaluated. The
      excellent and good rate of surgery was evaluated by using the Odom criteria.
      Harrison method was used to measure cervical curvature. The Cobb angle of the
      surgical segment was measured on the X-ray, and the range of motion (ROM) was
      calculated. The changes of the cervical curvature and the surgical segment ROM
      were compared pre- and post-operation. Results: The operation time was 94.1 min
      (range from 80 to 150 min). The average length of hospital stay was 4.8 days. The
      mean follow-up period was 23.5 months (range from 15 to 35 months). The
      preoperative arm VAS score was 6.95+/-0.88, 1-week postoperative arm VAS score
      was 2.09+/-0.67, the last follow-up arm VAS score was 1.04+/-0.98. The
      preoperative neck VAS score was 3.04+/-0.77, 1-week postoperative neck VAS score
      was 1.52+/-0.51 and the last follow-up neck VAS score was 0.61+/-0.78. The 1-week
      postoperative and last follow-up arm and neck VAS scores were significantly
      reduced compared with pre-operation (P<0.01). Compared with 1 week after surgery,
      the last follow-up of the arm and neck VAS score further reduced, the difference
      was statistically significant (P<0.01). The preoperative NDI was (58.52+/-4.98)%,
      the 1-week postoperative NDI was (33.74+/-4.72)%, the last follow-up NDI was
      (19.22+/-3.23)%. The 1-week postoperative and last follow-up NDI was
      significantly improved compared with pre-operation (P<0.01). Compared with 1 week
      after surgery, the last follow-up of the NDI further improved, the difference was
      statistically significant (P<0.01). The 1-week postoperative cervical curvature
      was (14.65+/-2.89) degrees , and it was improved compared with
      preoperative(14.23+/-3.06) degrees , the difference was statistically significant
      (P<0.05) . The last follow-up was cervical curvature(14.64+/-2.68) degrees ,
      there was no significant difference compared with preoperative (P> 0.05). The
      preoperative surgical ROM was(5.37+/-1.83) degrees , 1-week postoperative
      was(5.53+/-1.52) degrees , and the last follow-up was (5.62+/-1.48) degrees ,
      there was no significant difference pre-operative and post-operation (P> 0.05).
      The excellent and good rate was 91.3% (excellent in 16 cases, good in 5 cases, 2
      cases). There was no nerve root injury, cerebrospinal fluid leakage, wound
      infection, and other complications. Conclusions: PPECD is a sufficient and safe
      supplement for cervical disc herniation, its recent clinical efficacy was good.
      And it has no significant effect on cervical stability.

PMID- 29224268
TI  - [Applied anatomy study of posterior approach via sacrectomy for reaching the deep
      intrapelvic sacral plexus].
AB  - Objective: To observe the possibility of posterior approach via sacrectomy for
      reaching intrapelvic sacral plexus and expose the deep intrapelvic origin of
      sciatic nerve from sacral plexus in order to perform nerve graft. Methods: Five
      adult cadaver specimens were used in the study with prone position in May 2012.
      Cut off the gluteus maximus along the origins and lift to the lateral side, the
      piriformis was lay beneath. The sciatic nerve and the inferior gluteal nerve
      pierced from the infrapiriformis foramen in the operative field. Excise the
      origin of the piriformis via sacrectomy with osteotome and the length and width
      of the insertion on sacrum were measured. The piriformis was resected and then
      the sacral nerve roots beneath were exposed. The S2-S4 sacral nerve roots and the
      deep intrapelvic origin of sciatic nerve from sacral plexus were revealed after
      carefully dissecting. From July 2012 to June 2016, nine patients with lumbosacral
      plexus injury were performed surgery through the posterior approach in Department
      of Hand Surgery, Beijing Jishuitan Hospital.There were 6 male and 3 female
      patients, with a mean age of 29 years. All patients were diagnosed as upper and
      lower sacral plexus injury, in one of them combing with contralateral lower
      sacral plexus injury. The average time from injury to operation was 8.3 months.
      Results: The length and width of the piriformis insertion on sacrum were (3.44+/
      0.15) cm and (2.42+/-0.11) cm, respectively. The deep intrapelvic origin of
      sciatic nerve from sacral plexus in all nine patients can be revealed clearly and
      there was enough operative space that nerve transfer or graft can be performed
      through the posterior approach via sacrectomy. The total blood loss during
      operation was (1 822+/-1 523) ml. Conclusion: The piriformis and part of sacrum
      it attached can be resected safely through the posterior approach and the deep
      intrapelvic sacral plexus and the origin of sciatic nerve can be well exposed.

PMID- 29224269
TI  - [Surgical treatment and early-mid follow-up results of complete atrioventricular
      septal].
AB  - Objective: To discuss the surgical treatment and early-mid follow-up results of
      complete atrioventricular septal defect (CAVSD). Methods: The clinic data of 235
      cases of CAVSD underwent surgical treatment at Department of Cardiac Surgery,
      Guangdong General Hospital from June 2009 to June 2016 was analyzed
      retrospectively (104 male and 131 female patients). The patients were aged 18
      days to 58 years (mid age 8.9 months) at surgery, and 2 cases of newborns (0.9%),
      24 cases of 1 to 3 months (10.2%), 56 cases of 4 to 6 months (23.8%), 66 cases of
      7 to 12 months (28.1%), 36 cases of 1 to 3 years (15.3%), 37 cases of 4 to 18
      years (15.7%), and 14 cases above 18 years (6.0%). There were 129 cases of
      Rastelli type A (54.89%), 16 cases of type B (6.8%), 25 cases of type C (10.6%)
      and 65 cases of transitional type (27.7%). The patients were combined with 7
      cases of unroofed coronary sinus syndrome, 5 cases of coarctation of aorta, 4
      cases of tetralogy of Fallot, 3 cases of double outlet right ventricle, 1 case of
      transposition of the great arteries, 1 case of multiple ventricular septal
      defect, 1 case of pulmonary artery sling. The CAVSD correction operations were
      performed in 199 cases with modified single patch technique (84.7%), 26 cases
      with two patch technique (11.1%), 10 cases with conventional single patch
      technique (4.3%), and the corrective surgeries of other anomalies were performed
      in the meantime. Generalized Estimated Equation was used to statistical analysis
      of postoperative regurgitation level of mitral valve and tricuspid valve.
      Results: Followed-up for 1 to 7 years, 18 cases (7.7%) died overall and 15 cases
      (6.4%) died within 30 days post-operation.The mortality of little infant
      (operation age <=3 months) was much highest(26.9%). The mortality of different
      operation age had significant difference(P=0.007). There was no difference among
      the mortality with three techniques. Seven cases (3.0%) suffered from the re
      operation for severe mitral regurgitation. A total of 217 patients survived more
      than 1 year after initial surgery, and there were 11 cases (5.1%) with severe
      mitral regurgitation and 7 cases (3.2%) with severe tricuspid valve regurgitation
      at 1 year post-operation.The degree of mitral regurgitation after operation
      decreased at 1 week to 6 months, and slightly higher after 1 year
      postoperatively.The ratios of severe mitral regurgitation in different operative
      age group was statistically significant difference(P=0.017), mainly from 3 months
      group and 1 to 3 years group.The degree of tricuspid regurgitation decreased
      significantly after operation, and decreased gradually in the follow-up period.
      The ratio of postoperative residual severe tricuspid regurgitation was the
      highest in surgical aged >18 years old, less in 3 years group, the lowest in 3 to
      18 years group. Conclusions: The mortality and the ratio of patients with serious
      mitral regurgitation were higher in infants less 3 months than elder patients.
      The infants need more frequently follow-up and medicine treatment after
      operation. The modified one patch technique is effective for all age groups.

PMID- 29224270
TI  - [Diagnosis and treatment of adrenal ganglioneuroma: a report of 80 cases].
AB  - Objective: To review and discuss the experience of diagnosis and treatment of
      adrenal ganglioneuroma. Methods: Clinical data of 80 cases of adrenal
      ganglioneuroma undergoing surgery during January 1982 to May 2017 at Peking Union
      Medical College Hospital were retrospectively analyzed. There were 36 male and 44
      female patients. Age ranged from 8 to 69 years old (mean 37.7 years old). The
      tumor diameter were 1.5 to 18.0 cm (mean 4.3 cm). There were 61 cases of adrenal
      ganglioneuroma diagnosed by imaging examination. All patients underwent
      adrenalectomy. Results: All procedures were performed successfully without
      serious complication. Including 15 open surgery and 64 retroperitoneal
      laparoscopic surgery. One laparoscopic case conversion to open surgery. The
      pathological diagnosis was adrenal ganglioneuroma. Fifteen cases were mixed with
      other tumor components. No recurrence or metastasis was observed during the
      follow-up of 2 months to 35 years. Conclusions: The diagnostic techniques for
      adrenal ganglioneuroma are helpful to judge the tumor property before operation.
      The laparoscopic surgery has become the current method for resecting tumors. It
      shows advantages of small trauma and speedy recovery. The relationship between
      tumor and surrounding tissues should be understand clearly before operation. Full
      preparation must be made before operation if adrenal ganglioneuroma mixed with
      other tumor components.

PMID- 29224271
TI  - [Clinical features and prognosis of rare subtypes of renal cell carcinoma].
AB  - Objective: To investigate the clinical features and prognosis of rare subtypes of
      renal cell carcinoma. Methods: This retrospective study collected the data of 52
      rare subtypes of renal cell carcinoma of patients who underwent surgery from
      January 2002 to December 2014 at Department of Urology, Peking University First
      Hospital. There were 12 patients with collecting duct carcinoma, 5 patients with
      Xp11.2 translocation renal cell carcinoma, 5 patients with mucinous tubular and
      spindle cell carcinoma, 30 patients with unclassified renal cell carcinoma. The
      study group included 25 male and 27 female patients, with mean age of 52 years.
      The mean tumour size was (6.5+/-3.9) cm (range: 1.5 to 21.0 cm). The basic
      clinical features, gross appearance, Fuhrman nuclear grade, TNM staging and
      prognosis of rare subtypes of RCC were studied. The OS curves were obtained for
      rare subtypes of renal cell carcinoma using the Kaplan-Meier method and compared
      using a Log-rank test. Results: The rate of lymph node and distant metastasis
      were 34.6% (18/52) and 17.3% (9/52). Malignancies were screened and detected by
      color Doppler ultrasonography or CT scan, however, no case was diagnosed before
      operation or aspiration, all cases were confirmed by the pathological
      examination. The average period of postoperative follow-up process was 65 months,
      and the mean survival time was (34+/-23) months. Conclusion: The clinical
      features of rare subtypes of renal cell carcinoma are similar to those of clear
      cell renal cell carcinoma, while the imaging changes will be helpful for
      diagnosis before operation.

PMID- 29224272
TI  - [The development and status of bioartificial liver].
AB  - Liver failure is a serious stage during liver disease development of which
      mobidity is high. There is no effective treatment at present.Artificial liver
      support system is one of the important methods to treat liver failure which
      includes non-biological artificial liver, biological artificial liver and hybrid
      artificial liver. Among the artificial liver devices. The bioartificial liver is
      the most similar artifical liver device to human liver in terms of
      detoxification, synthesis and metabolism currently.The complexity of human liver
      function makes the biological artificial liver facing great challenges in
      selection of liver seed cells, construction of bioreactor and the best
      combination with auxiliary device, which leads to the slow development of
      bioartificial liver. In order to provide theoretical support for the study of
      bioartificial liver, the current status and its development are reviewed in the
      following aspects, the source of seed cells, the construction of bioreactor, the
      combination of auxiliary devices and the clinical application of bioartificial
      liver in this article.

PMID- 29224273
TI  - [Ki-67 expression and its effect on response to neo-adjuvant chemotherapy in
      invasive breast cancer].
AB  - Objective: To investigate the response to neoadjuvant chemotherapy (NAC) among
      different molecular subtypes of breast cancers using molecular classification
      with Ki-67 (ER+ PR+ HER2+ Ki-67) or without Ki-67 (ER+ PR+ HER2). Methods: One
      hundred and twenty-seven cases of invasive breast cancer confirmed by core needle
      biopsy before NAC were collected from January 2007 to December 2009 and diagnosed
      at West China Hospital, Sichuan University. The cases were classified into
      different molecular subtypes using molecular classifications with or without Ki
      67. Their clinical and pathological response to NAC was evaluated and compared.
      Results: The different subtypes using both molecular classifications showed
      significant difference in clinical response(with Ki-67: chi(2)=22.40, P<0.01;
      without Ki-67: chi(2)=9.202, P=0.027)but not pathological(P>0.05) response to
      NAC. By multivariate analysis, Ki-67 was predictive for a clinical complete
      response (P=0.041) and clinical overall response (P<0.01); also Ki-67 was the
      only clinicopathological factor predictive of pathological response(P=0.041).
      Conclusion: The molecular classification with Ki-67 is better to predict breast
      cancers responsiveness to NAC than the molecular classification without Ki-67.

PMID- 29224274
TI  - [Correlation analysis of PD-L1 expression and prognosis in triple-negative breast
      cancers].
AB  - Objective: To investigate the relationship between PD-L1 expression and the
      clinicopathologic features and prognosis in triple-negative breast carcinomas
      (TNBC). Methods: All 142 cases of TNBC were collected from the First Affiliated
      Hospital of Nanjing Medical University from February 2011 to December 2014, and
      the surgical excision or biopsy specimens from patients without chemotherapy and
      radiotherapy were included. Histopathologic analysis of stromal tumor
      infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1
      immunohistochemical staining was done with MaxVision. Results: The PD-L1
      expression rate was 34.5% (49/142) in tumor cells, and was 62.0% (88/142) in
      sTIL. The PD-L1 expression in tumor cells was positively correlated with tumor
      size (r=0.181, P=0.031), Ki-67 index (r=0.211, P=0.012), sTIL (r=0.380, P<0.01)
      and PD-L1 expression in sTIL (r=0.447, P<0.01). The PD-L1 expression in sTIL was
      positively correlated with tumor grade (r=0.215, P=0.01), Ki-67 index (r=0.253,
      P=0.002) and sTIL (r=0.370, P<0.01). The high stromal CD8(+) /FOXP3(+) ratio was
      significantly associated with improved overall survival (chi(2)=4.186, P=0.041).
      The high percentage of sTIL was significantly associated with improved overall
      survival (chi(2)=12.427, P<0.01) and progression-free survival (chi(2)=4.057,
      P=0.044). Conclusions: In TNBC, PD-L1 expression is positively correlated with Ki
      67 and sTIL; the stromal CD8(+) /FOXP3(+) ratio and sTIL are significantly
      associated with prognosis. The PD-L1 expression, stromal CD8(+) /FOXP3(+) ratio
      and sTIL are biologically important in TNBC, and all these correlative factors
      are important potential parameters in assessing immunotherapy for TNBC.

PMID- 29224275
TI  - [Clinicopathologic study of infiltrating epitheliosis of the breast].
AB  - Objective: To evaluate the morphological and immunohistochemical features of
      infiltrating epitheliosis and its differential diagnosis. Methods: Nine
      consultation and routine cases of infiltrating epitheliosis diagnosed from
      January 2015 to December 2016 in Fudan University Shanghai Cancer Center were
      collected. All tissues were formalin-fixed paraffin-embedded and routinely HE
      stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7,
      CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein
      was performed using Ventana BenchMark automated immunostainer. Results: The
      morphological features of infiltrating epitheliosis included: (1) Florid
      proliferation of epithelial cells forming solid nests or papillary, glandular and
      cord-like pattern. The proliferative cells possessed nuclei of varying size and
      shape without atypia. (2) The stroma was altered, showing varying degrees of
      fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the
      spaces within small ducts and lobules at the periphery of the lesion, resulting
      in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non
      uniformly positive for ER/PR, and was positive for high molecular weight CK5/6
      and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact,
      partial or entire loss of myoepithelial cells around the epithelial nests. The
      loss of myoepithelial markers staining was more frequent at the periphery of the
      lesion. The most important differential diagnoses included invasive ductal
      carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous
      carcinoma, etc. Conclusions: Infiltrating epitheliosis is an important pseudo
      infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity
      for high molecular weight cytokeratins, and the intact to partial to entire loss
      of myoepithelial markers around the proliferating cell nests are the key points
      to differentiate it from invasive carcinomas and DCIS.

PMID- 29224276
TI  - [Expression and mechanism of Twist2 in glioma].
AB  - Objective: To investigate the significance of Twist2 in glioma and whether it is
      involved in the malignant transformation of glioma by epithelial-mesenchymal
      transition (EMT). Methods: Using immunohistochemical method detected the
      expression level of Twist2 in 60 cases of gliomas (including WHO grades II, III
      and IV, each for 20 cases) and 20 cases of non-tumor brain tissues. Real-time
      fluorescence quantitative PCR and Western blot were used to detect the expression
      level of Twist2 mRNA and protein in 61 cases of fresh glioma tissue (WHO grade II
      16 cases, III 21 cases, IV 24 cases) and 12 cases of adjacent tissues, and the
      expression levels of E-cadherin, N-cadherin and vimentin were also investigated
      in fresh glioma tissue. Results: Immunohistochemistry results showed that the
      percentages of Twist2 expression in glioma was 90%(54/60) compared with 30%(6/20)
      in non-tumor brain tissues(P<0.01). The percentages of Twist2 expression were 75%
      (15/20), 95% (19/20), and 100% (20/20) in the WHO gradesII, III and IV gliomas,
      respectively. WHO grades IV and III were significantly higher than that of WHO
      grade II (P<0.01). There was no significant difference between WHO grade IVand
      WHO III glioma (P>0.05). Real-time fluorescence quantitative PCR and Western blot
      showed that the expression level of Twist 2 in gliomas was significantly higher
      than that in para-cancerous tissues (P<0.01), and those in WHO grades IV and III
      gliomas were significantly higher than that in WHO grade II glioma (P<0.01).
      There was no significant difference between WHO grade IVand grade III glioma
      (P>0.05). Detection of key protein expression in EMT by Western blot displayed
      that the expression of E-cadherin was negatively associated with Twist2 in glioma
      (r=-0.972, P<0.01). The expression of N-cadherin and vimentin was positively
      associated with Twist2 in glioma(r=0.971, P<0.01; r=0.968, P<0.01). Conclusions:
      The expression of Twist2 in human glioma is positively correlated with the
      malignant grade of glioma, which may be involved in the malignant progression of
      glioma by EMT.

PMID- 29224277
TI  - [Clinicopathologic analysis of micronodular thymoma with lymphoid stroma].
AB  - Objective: To investigate the clinicopathologic features of micronodular thymoma
      with lymphoid stroma(MNT). Methods: Five cases of MNT diagnosed from January 2007
      to December 2016 in Henan Provincial People's Hospital were collected.Hematoxylin
      Eosin staining and immunohistochemistry were used to evaluate the histological
      and immunophenotypic characteristics in 5 MNT cases. Epstein-Barr virus (EBV)
      status was detected by in situ hybridization for EBV-encoded small RNA (EBER).
      Polymerase chain reaction was used to detect the rearrangement of immunoglobulin
      genes. Results: Five cases were MNT, including 3 male and 2 female patients, mean
      aged 59 years (from 43 to 63 years). All patients had ananterior mediastinal
      mass, with no myasthenia gravis and autoimmune diseases, and underwent surgical
      resection.Half to ten years follow-up showed no recurrence.Grossly, the tumors
      were solid in 4 cases, and cystic and solid in 1 case; the border was clear.
      Histologically, the tumors presented as a distribution of micronodules separated
      by abundant lymphoid stroma with prominent germinal centers. The nodules were
      composed of neoplastic spindle, oval cells containing bland, oval
      nuclei.Immunohistochemical study showed strong positivity of the tumor cells for
      CKpan, CK19, CK5/6 and p63. Stains for EMA, CD117, calretinin, TTF1 were negative
      in the tumor cells.Scattered CD3, CD1a, and TdT positive immature T lymphocytes
      were noted in and around tumor nodules. Many lymphocytes in the stroma, including
      germinal centers, were positive for CD20.The bcl-2 was also detected in
      lymphocytes in the stroma, mantle and marginal zone of lymphoid follicles, and in
      part of tumor cells. Tumor cells and lymphocytes were negative for EBER.
      Immunoglobulin genes rearrangement analysis showed that B lymphocytes were
      polyclonal. Conclusions: MNT is a rare thymoma, which occurs in the elderly and
      has no obvious symptom. After complete resection, the prognosis is very good. The
      diagnosis should be based on a combination of clinicopathologic features, and
      other types of thymoma should be excluded.

PMID- 29224278
TI  - [Clinicopathologic and molecular genetic characterizations of biphenotypic
      sinonasal sarcoma].
AB  - Objective: To investigate the clinicopathologic characteristics,
      immunophenotypes, molecular genetics, and diagnostic and differential diagnostic
      features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS
      were retrieved, the histomorphology, immunophenotype and molecular genetics were
      analyzed with review of literature. Results: There were 2 male and 1 female
      patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic
      resonance imaging examinations showed a large polypoid mass occupying the
      sinonasal cavity in all 3 patients. Microscopically, these tumors were un
      circumscribed and composed of cellular spindle-shaped cells arranged in long and
      interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently
      identified. The overlying hyperplastic respiratory epithelium invaginated down
      into the tumor forming a cystic (2 cases), glandular (1 case) structures and
      inverted in a papilloma-like (1 case)pattern, and foci of eosinophilic metaplasia
      were also noted in 2 of the three cases. The tumor nuclei were bland-appearing,
      mitoses were scarce and necrosis was absent. Immunohistochemically, the tumor
      cells showed co-expression of neural and myogenic markers in all the 3 cases,
      including that 3/3 showed diffuse and strong positivity of S-100 protein, 3/3
      positivity of smooth muscle actin (1 diffuse and 2 focal), 1/2 diffuse positivity
      of calponin, 1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In
      addition, 1 detected for beta-catenin showed focal nuclear positivity. None of
      the 3 showed positivity to cytokeratin, CD34 or SOX10 in the tumor cells.Ki-67
      showed an index <5%, 10% and <2%, respectively. Fluorescence in situ
      hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case
      3, reverse transcription polymerase chain reaction, followed by Sanger
      sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up
      information (range 3-15 months)showed no evidence of local recurrence or distant
      metastasis in three cases. Conclusions: BSNS is a newly described entity which
      can be readily confused with a variety of benign and malignant spindle cell
      tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of
      neural and myogenic markers and PAX3 gene rearrangement can help distinguish this
      tumor from its many mimickers.

PMID- 29224280
TI  - [Invasive papillary carcinoma of breast: clinicopathologic analysis of 6 cases].

PMID- 29224279
TI  - [Overexpression of TRPV1 after periphery nerve injury attenuates nerve
      regeneration in rats].
AB  - Objective: To observe the effect of the expressive or functional blockage of
      TRPV1 on nerve regeneration after sciatic trans-section injury. Methods: AMG-517,
      a kind of TRPV1 inhibitor, was injected into the surrounding area of the
      ipsilateral lumbar dorsal root ganglia while unilateral sciatic nerve was
      transected. A total of 24 healthy male Sprague-Dawley rats were divided into 4
      groups: control group, injury only group, injury+ AMG-517 150 MUg/kg group,
      injury+ AMG-517 300 MUg/kg group. The injury only group was injected the same
      volume of medium. The release of CGRP from dorsal-horn of spinal cord, the number
      of axons at proximal stem of sciatic nerve after transection, and the expression
      of TRPV1 in dorsal root ganglion were detected using the methods of ELISA,
      Western blot and semi-thin section (1 MUm)- toluidine blue staining 2 weeks after
      injury. Results: The release of CGRP in lumbar spinal dorsal horn was obviously
      decreased after AMG-517 treatment, which was the evidence of TRPV1 functional
      inhibition. CGRP in the control group was 0.15 ng/g, the injury only group 0.17
      ng/g, AMG-517 150 MUg/kg group 0.09 ng/g, and AMG-517 300 MUg/kg group 0.11
      ng/g(P<0.01). The number of axons which were myelinated or unmyelinated increased
      after the TRPV1 was inhibited by AMG-517(P<0.01). In addition, the injection of
      AMG-517 into surrounding dorsal root ganglion decreased the expression of TRPV1
      in dorsal root ganglion(P<0.01). Conclusions: Over expression or activation of
      TRPV1 after periphery nerve injury has negative effect on nerve regeneration in
      fact; Inhibiting the over-expression or over-activation of TRPV1 after nerve
      injury facilitates axonal regeneration and nerve repair.

PMID- 29224281
TI  - [Clinicopathologic characteristics of 64 patients with AFP-producing gastric
      cancer].

PMID- 29224283
TI  - [Spindle-shaped diffuse large B-cell lymphoma of ovary: report of a case].

PMID- 29224282
TI  - [Clinicopathologic characteristics of pancreatoblastoma].

PMID- 29224284
TI  - [Clinicopathologic features of Lynch syndrome with endometrial carcinoma combined
      with gastric cancer, colon cancer and rectal cancer: report of a case].

PMID- 29224285
TI  - [Severe diarrhea associated with ganglioneuromatosis in elderly: report of a
      case].

PMID- 29224286
TI  - [Primary malignant melanoma of trachea: report of a case].

PMID- 29224287
TI  - [Mycobacterium marinum infection: report of a case].

PMID- 29224288
TI  - [Indolent lymphoproliferative disorder and lymphoma].

PMID- 29224289
TI  - [Ets transcription factors in pathogenesis of breast cancer].

PMID- 29224290
TI  - [Clinicopathologic characteristics of peripheral squamous cell carcinoma of
      lung].

PMID- 29224291
TI  - [Advances in relationship between PTEN and myocardial fibrosis].

PMID- 29224292
TI  - [Roles of osteogenic niche in malignant tumor with bone metastasis].

PMID- 29224293
TI  - [Development of diagnosis and treatment of chronic obstructive pulmonary disease
      needs participatory and personalized].

PMID- 29224296
TI  - [Lung function test in Chinese COPD patients: challenge and strategy].

PMID- 29224294
TI  - [Analysis of COPD management in China based on health insurance data].

PMID- 29224295
TI  - [Respiratory support strategy and mode selection in acute exacerbation of COPD].

PMID- 29224297
TI  - [Tobacco cessation is the most effective intervention for the prevention and
      treatment of obstructive pulmonary disease].

PMID- 29224298
TI  - [Smoking abstinence rate and its associated factors between abrupt and gradual
      smoking cessation].
AB  - Objective: To analyze and compare the abstinence rate of smoking quitting methods
      and its associated factors between abrupt and gradual smoking cessation in
      smokers with drug-based therapy. Methods: A prospective clinical study was
      conducted in patients undergoing quitting smoking intervention in Ruijin Hospital
      smoking cessation clinic between June 2013 and May 2016. All the subjects were
      randomized in a 1?1 ratio into the abrupt smoking cessation group (smoking as
      usual over 3 weeks before a planned quit day, and then stopping smoking abruptly)
      and the gradual smoking cessation group (gradually reducing tobacco use over 3
      weeks before a planned quit day, and then stopping smoking totally). The primary
      outcome was the complete abstinence rate, and the secondary outcomes included 1
      month, 3-month and 6 month 7-day point prevalence of abstinence rates and 3 month
      sustained abstinence rates. Changes of body weight and drug adverse events were
      also compared. Results: A total of 314 moderate to severe nicotine-dependent
      patients were admitted in the study, including 157 patients in the abrupt smoking
      cessation and 157 patients in the gradual smoking cessation group. Fourteen
      patients fell off during the follow-up. For the complete abstinence rate, the
      gradual smoking cessation group was higher than the abrupt smoking cessation
      group(55.0% vs. 36.9%, chi(2)=9.841, P=0.002) .For 7-d smoking abstinence rate in
      the 1st, 3rd, 6th month, there was no significant difference between the 2 groups
      (all P>0.05). As for the 3-month sustained abstinence rate, a higher smoking
      quitting rate was seen in the gradual smoking cessation group compared to the
      abrupt smoking cessation group in the 6-month follow-up (17.9% vs.8.7%,
      chi(2)=5.441, P=0.020). The adverse drug reaction incidence was higher in the
      abrupt smoking cessation group than the gradual smoking cessation group
      (Gastrointestinal discomfort: 39.2% vs. 17.7%, chi(2)=12.336, P=0.000;
      Dreaminess: 40.2% vs. 13.3%, chi(2)=20.172, P=0.000). Conclusions: For moderate
      to severe nicotine-dependent patients, the gradual smoking cessation could serve
      to enhance the abstinence rate and mitigate the withdrawal symptoms.

PMID- 29224299
TI  - [Correlation analysis of serum secreted frizzled-related protein 5 levels with
      airway inflammation and insulin resistance in chronic obstructive pulmonary
      disease patients].
AB  - Objective: To investigate the relationship between serum secreted frizzled
      related protein 5(sfrp5) levels, insulin resistance, and airway inflammation in
      patients with chronic obstructive pulmonary disease(COPD). Method: A total of 178
      COPD patients visiting our respiratory outpatient clinic from February 2015 to
      January 2017 were enrolled, and 99 healthy control subjects from the same time
      period were selected. Serum sfrp5 levels were compared between the 2 groups.
      Serum sfrp5 and inflammatory cytokines in induced sputum were observed in the 4
      subgroups: insulin resistant COPD group [homeostasis model assessment of insulin
      resistance (HOMA-IR)>=2.29], non-insulin resistant COPD group, non-COPD insulin
      resistant group, and healthy control group. Results: Serum sfrp5 levels were
      found to be significantly higher in the COPD group as compared to the healthy
      control group (t=-14.29, P<0.001). Serum sfrp5 levels in the insulin resistant
      COPD group [(8+/-3)ng/ml] were significantly lower than that of the non-insulin
      resistant COPD group [(10+/-5)ng/ml], non-COPD insulin resistant group [(13+/
      3)ng/ml], and normal control group [(14+/-4)ng/ml, F=35.85, P<0.01]. The insulin
      resistant COPD group had higher levels of In(Homa-IR), as well as tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in induced sputum as compared
      to the non-insulin resistant COPD group, non-COPD insulin resistant group, and
      healthy control group (F values were 64.968, 41.40, 64.15, respectively, P value
      <0.01 for all items). The non-insulin resistant COPD group had higher levels of
      In(HOMA-IR) as well as TNF-alpha and IL-6 in induced sputum as compared to the
      non-COPD insulin resistant group and healthy control group. FEV(1)/FVC and
      FEV(1)% predicted were significantly lower in the insulin resistant COPD group as
      compared to those of non-insulin resistant COPD group and non-COPD insulin
      resistant group, and healthy control group (F values were 2.481 and 8.37,
      respectively, P value<0.05 for all items). FEV(1)/FVC and FEV(1)% predicted were
      significantly lower in the non-insulin resistant COPD group as compared to those
      of the healthy control group and non-COPD insulin-resistant group. Serum sfrp5
      levels were positively correlated to FEV(1)/FVC and FEV(1) predicted (r values
      were 0.466 and 0.412, respectively; P values were <0.001 and 0.007, respectively)
      and inversely correlated to In(HOMA-IR) and TNF-alpha and IL-6 in induced sputum
      (r values were -0.304, -0.459, -0.517, respectively; P values were <0.001, 0.002,
      <0.001, respectively). BMI, ln(HOMA-IR), and IL-6 in induced sputum were
      independent related factors (r(2) values were 0.286, 0.176, 14.69, respectively;
      P values were <0.01 for all items) Conclusion: Sfrp5 may be concurrently
      associated with COPD and insulin resistance; insulin resistance may be associated
      with airway inflammation and airflow limitation. Sfrp5 may be involved in the
      development of COPD and may be the key link by which insulin resistance exerts
      its effects on airway inflammation.

PMID- 29224300
TI  - [Etiological analysis and establishment of a discriminant model for lower
      respiratory tract infections in hospitalized patients].
AB  - Objective: To analyze the pathogens of lower respiratory tract infection(LRTI)
      including bacterial, viral and mixed infection, and to establish a discriminant
      model based on clinical features in order to predict the pathogens. Methods: A
      total of 243 hospitalized patients with lower respiratory tract infections were
      enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The
      clinical data and airway (sputum and/or bronchoalveolar lavage) samples were
      collected. Microbes were identified by traditional culture (for bacteria), loop
      mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and
      atypical pathogen), or Real-time quantitative polymerase chain reaction (Real
      time PCR)for viruses. Finally, a discriminant model was established by using the
      discriminant analysis methods to help to predict bacterial, viral and mixed
      infections. Results: Pathogens were detected in 53.9% (131/243) of the 243
      cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1
      case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and
      Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with
      the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia.
      Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma
      pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly
      Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus,
      human parainfluenza virus, respiratory syncytial virus, human metapneumovirus,
      human boca virus were also detected fewly. Seven parameters including mental
      status, using antibiotics prior to admission, complications, abnormal breath
      sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index
      (PSI) score and CRUB-65 score were enrolled after univariate analysis, and
      discriminant analysis was used to establish the discriminant model by applying
      the identified pathogens as the dependent variable. The total positive predictive
      value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral
      infection and 33.3% for the mixed infection. Conclusions: The mostly detected
      pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella
      pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients
      with LRTI in this hospital. The discriminant diagnostic model established by
      clinical features may contribute to predict the pathogens of LRTI.

PMID- 29224301
TI  - [Application of bispectral index monitoring in sedation and analgesia for
      flexible bronchoscopy].
AB  - Objective: To investigate the feasibility of using bispectral index monitoring in
      sedation and analgesia for bronchoscopy. Methods: Totally 285 patients admitted
      to the Respiratory Medicine Department of Nanjing First Hospital for bronchoscopy
      between June 2016 and December 2016 were assigned, according to their own wishes,
      into a conscious sedation group (171 cases receiving local anesthesia and
      conscious sedation, 89 males, 82 females, mean age 59+/-10 years) and a control
      group (114 cases undergoing local anesthesia, 59 males, 55 females, average age
      61+/-12 years). The 2 groups were compared in terms of operation time, blood
      pressure, heart rate and other indicators during bronchoscopy including incidence
      of adverse events, memory of the procedure, willingness to be re-examined, safety
      of sedation and analgesia for bronchoscopy under bispectral index monitoring, and
      patient satisfaction in the postoperative follow-up. Results: The conscious
      sedation group and the control group had no difference in age and sex
      ratio(P>0.05). Compared with the patients in the control group(operation time
      16+/-5 min and systolic blood pressure 153+/-21 mmHg, 1 mmHg=0.133 kPa), those in
      the conscious sedation group had a shorter operation time(14+/-5 min) and a lower
      systolic blood pressure(144+/-22 mmHg), with statistically significant difference
      (P<0.01). There was no significant difference in diastolic blood pressure and
      heart rate (89+/-14 mmHg and 84+/-17 times/min in the conscious sedation group
      and 92+/-12 mmHg and 87+/-14 times/min in the control group, P>0.05). Adverse
      events, overall intraoperative cough and bleeding were found to be significantly
      reduced in the conscious sedation group (27%, 4% and 13% and 60%, 13% and 35% in
      the control group, P<0.01), but transient hypoxia was not (12% in the conscious
      sedation group, and 14% in the control group, P=0.72). Patient satisfaction and
      willingness to be re-examined were markedly higher in the conscious sedation
      group (97%) than in the controls (4%, P<0.01). Conclusions: Bispectral index
      monitoring is safe in sedation and analgesia for bronchoscopy and has higher
      patient satisfaction, suggesting that it is a potential tool for use in clinical
      practice.

PMID- 29224302
TI  - [Clinical and radiological features of adult patients with different
      antisynthetase syndrome based on serum anti-aminoacyl-tRNA synthetase antibody
      type].
AB  - Objective: To describe the clinical and radiological characteristics of
      antisynthetase syndrome associated interstitial lung disease in patients with
      different serum anti-aminoacyl-tRNA synthetase antibodies. Methods: We conducted
      a retrospective analysis of 5 adult patients with antisynthetase syndrome
      associated interstitial lung disease in Peking Union Medical College Hospital.
      Their clinical and chest radiological data were analyzed and relevant literatures
      were reviewed. Results: Among these 5 patients, there were 1 male and 4 females,
      aged from 32 y to 67 y, with a mean age of 53 y. Cough and exertional dyspnea
      were the main clinical complaints. Four cases showed mechanic's-like hands, and
      all of the 5 cases had Velcro rales in the basal lungs. None of them showed
      clubbing. Creatine kinase was elevated in 1 case with anti-Jo-1 synthetase
      antibody, and anti-nuclear antibody was positive in 4 cases, with different
      titers from 1?80 to 1?320, and anti-Ro-52 antibody was positive in 3 cases. Anti
      aminoacyl-tRNA synthetase antibody spectrum analysis showed 1 case with anti-Jo
      1, 1 anti-PL-7, 1 anti PL-12, 1 anti-EJ and 1 anti-OJ synthetase antibody,
      respectively. Chest high resolution CT showed nonspecific interstitial pneumonia
      pattern in 1 case, and nonspecific interstitial pneumonia pattern with organizing
      pneumonia pattern in 4 cases. All the cases responded to immunosuppressive
      therapy including corticosteroids (with starting prednisone dosage more than 1
      mg.kg(-1).d(-1)) plus azathioprine or Mycophenolate mofetil. Conclusions:
      Antisynthetase syndrome associated interstitial lung disease, characterized by
      the presence of different anti-tRNA synthetase antibodies, is an increasingly
      recognized clinical entity. Clinical and radiological features of different
      subtypes of antisynthetase syndrome are relatively heterogeneous. Nonspecific
      interstitial pneumonia pattern, nonspecific interstitial pneumonia pattern with
      organizing pneumonia pattern and organizing pneumonia pattern were common chest
      HRCT patterns. Prednisone plus immunosuppressive agents are the recommended first
      line therapy.

PMID- 29224303
TI  - [Atypical computed tomography manifestations of thoracic sarcoidosis].
AB  - Objective: This study evaluated the atypical computed tomography (CT)
      manifestations of thoracic sarcoidosis. Methods: Medical data of 190 patients
      with thoracic sarcoidosis were retrospectively reviewed. Results: The atypical CT
      manifestations of thoracic sarcoidosis observed were unilateral hilar
      lymphadenopathy with or without mediastinal lymphadenopathy(n=12, 6.3%),
      mediastinal lymphadenopathy without hilar lymphadenopathy(n=9, 4.7%), patchy
      consolidation (n=23, 12.1%), sarcoid galaxy sign (n=22, 11.6%), reversed halo
      sign (n=1, 0.5%), and ground-glass opacities (n=52, 27.4%). Air trapping was
      found in 8 of 10 patients who underwent both inspiratory and expiratory CT. Post
      treatment CT scans showed improvements in most patients. Of the 12 patients with
      unilateral hilar lymphadenopathy with or without mediastinal lymphadenopathy,
      10(83.3%) improved. Of the 9 patients with mediastinal lymphadenopathy without
      hilar lymphadenopathy, 8(88.9%) improved. Of the 23 patients with patchy
      consolidation, 15(65.2%) improved. Of the 22 patients with the sarcoid galaxy
      sign, 16(72.7%) improved. The patient with the reversed halo sign improved
      completely. Of the 52 patients with ground-glass opacities, 31(59.6%) improved.
      Of the 8 patients with air trapping, 7(87.5%) improved. Conclusions: The atypical
      imaging manifestations of thoracic sarcoidosis included unilateral hilar
      lymphadenopathy with or without mediastinal lymphadenopathy, mediastinal
      lymphadenopathy without hilar lymphadenopathy, patchy consolidation, the sarcoid
      galaxy sign, the reversed halo sign, ground-glass opacity, and air trapping.
      These lesions mostly improved after treatment. Familiarity with these atypical
      signs will help increase the diagnostic accuracy of imaging studies for thoracic
      sarcoidosis.

PMID- 29224305
TI  - [Recent advance in impacts of pulmonary rehabilitation on inflammation and
      oxidative stress in chronic obstructive pulmonary disease].

PMID- 29224304
TI  - [Method for recording tension changes of small pulmonary artery and vein using
      the isolated vessel tension measurement system].
AB  - Objective: To establish a standardized method for isolated pulmonary artery and
      vein rings with different diameter, pressure and length, which could provide a
      more scientific method for in vitro study of pulmonary vessel diseases. Methods:
      Male SD rats were anesthetized, and the right ventricular systolic pressure were
      measured. Small pulmonary artery and vein rings with 200-400 MUm in diameter and
      2 mm in length were prepared by dissecting pulmonary arteries and veins. The
      pulmonary vessel rings were mounted in the organ bath by 2 stainless steel wires
      with diameter of 40 MUm. Then the internal circumference of the vessel rings was
      increased gradually with 100 MUm per step. At the same time the vascular tension
      was recorded by the Myograph System and Acknowledgement data acquisition system,
      and subsequently the passive length-tension exponential curve was made. The
      initial tension of the rings was set, equilibrated for another 30 min, and then
      stimulated with 60 mmol/L KCl 3 times, and the best contractile reactivity was
      achieved. The contractile reactivity of pulmonary artery rings and endothelial
      integrity were detected by exposure to 1 MUmol/L phenylephrine(PE) and 10 MUmol/L
      acetylcholine(Ach), while the contractile reactivity of pulmonary vein rings was
      detected by exposure to 1 MUmol/L U46619 and 10 MUmol/L papaverine. Results: The
      contraction and relaxation effects of the pulmonary artery rings reached 0.39 mg
      and 92% when they were stimulated by 1 MUmol/L PE and 10 MUmol/L Ach. The
      contraction and relaxation effects of pulmonary vein rings were up to 0.13 mg and
      84% when they were exposed to 1 MUmol/L U46619 and 10 MUmol/L papaverine,
      respectively. Conclusion: Pulmonary artery and vein rings with appropriate basal
      tension and optimal vasodilator activity were prepared, and a standardized method
      of tension experiment for isolated pulmonary artery and vein rings established.

PMID- 29224306
TI  - [Early pulmonary rehabilitation research progress in patients with mechanical
      ventilation].

PMID- 29224307
TI  - [The advances in aerosol durg therapy research].

PMID- 29224308
TI  - [The development and application of digital PCR used in Mycobacterium
      tuberculosis detection].

PMID- 29224309
TI  - [Promote laboratory methods to improve the diagnosis for invasive fungal
      disease].

PMID- 29224310
TI  - [How I manage cytomegalovirus infection after hematopoietic stem cell
      transplantation].

PMID- 29224311
TI  - [How I treat febrile neutropenic patients with acute leukemia after
      chemotherapy].

PMID- 29224312
TI  - [How I diagnose and treat post-transplant lymphoproliferative disorders after
      allogeneic hematopoietic stem cell transplantation].

PMID- 29224313
TI  - [Incidence of blood stream infections of 1265 patients with hematopoietic stem
      cell transplantation and analysis of pathogenic bacteria].
AB  - Objective: To analyze the incidence and microbiological features of blood stream
      infections (BSI) of patients with hematopoietic stem cell transplantation (HSCT)
      and to provide laboratory data for empirical use of antibiotic for the HSCT
      patients with BSI. Methods: The incidence of bloodstream infection, the positive
      rate of blood culture, bacterial spectrum and drug resistance were analyzed in 1
      265 HSCT recipients during 2013 and 2015 were retrospectively studied. Results:
      Of 1265 patients undergoing HSCT, 1 422 cases of suspected BSI occurred in 784
      patients (61.98%) , and 464 patients (59.2%) were in the stage of agranulocytosis
      (ANC<0.5*10(9)/L) . The detection rate of pathogens in 2013-2015 was about 20%
      and increase year after year. Of the 401 strains detected, 221 were Gram-negative
      (G(-)) bacteria (55.1%) , 165 Gram-positive (G(+)) bacteria (41.2%) and 15 fungi
      (3.7%) . Escherichia coli (16.0%) , Staphylococcus epidermidis (15.5%) and
      Klebsiella pneumoniae (11.2%) were listed the top three. The proportion of
      multidrug resistant Acinetobacter Bauman and Stenotrophomonas maltophilia was
      64.70% and 63.64% respectively, and methicillin resistant Staphylococcus aureus
      (MRSA) was more than half (57.14%) . The ratio of vancomycin resistant
      Enterococci (VRE) and carbapenem resistant Enterobacteriaceae (CRE) was 14.29%
      and 6.78% respectively. More than 40% Enterobacteriaceae bacteria were resistant
      to three or four generation cephalosporin antibiotics, and less were resistant to
      the carbapenems (6.4%) . However, many non-fermentating bacteria were highly
      resistant to these antibiotics and showed diversity among different strains, with
      a rate of 47.8% resistance to carbapenems. All the Staphylococcus were sensitive
      to vancomycin, teicoplanin and linezolid. Conclusions: The incidence of BSI in
      patients with HSCT was high, and the pathogens were mainly G(-) bacteria. In
      addition to Enterobacteriaceae, the proportion of non-fermentative bacteria was
      quite high. No Staphylococcus detected were resistant to vancomycin, teicoplanin
      and linezolid.

PMID- 29224314
TI  - [Clinical value of PCR for viral detection of bronchoalveolar lavage fluid in the
      diagnosis and treatment of pneumonia after allogeneic hematopoietic stem cell
      transplantation].
AB  - Objective: To analyze the clinical value of real-time PCR for virus detection in
      the diagnosis and treatment of patients after allo-HSCT who had no infection
      evidence of pneumonia using routine pathogen detection panel. Methods: The
      clinical data of 71 episodes with acute lung injury from May 2015 to March 2017
      after allo-HSCT in hematology department of Peking University People's Hospital
      (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine
      pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF)
      samples. Results: Among 71 episodes with acute lung injury, a total of 15
      patients were diagnosed as lower respiratory tract disease merely associated with
      virus (detection rate of 21.13%) , 19 episodes were absent of lower respiratory
      tract infection. The median time from allo-HSCT to the occurrence of lung injury
      were 176 (49-1 376) d and 196 (57-457) d respectively (z=-0.191, P=0.864) . There
      were no statistical differences for baseline characteristics and clinical
      features between two groups. The 100-day attributable mortalities were 13.3%
      (2/15) and 26.3% (5/19) (chi(2)=0.864, P=0.426) . Patients with low-dose steroids
      treatment had favorable outcome than those with high-dose steroids treatment (the
      dose of methylprednisolone >=250 mg/d as standard) [4.2% (1/24) vs 60.0% (6/10)
      ]. In patients with detectable virus in BALF, 2 patients died with early high
      dose steroids treatment, while 11 patients survived with no steroids treatment or
      late application. Conclusions: Virus infection should be considered in post-HSCT
      pneumonia patient with negative result using routine pathogen detection panel.
      Expanding virus detection panel by PCR in BALF could increase diagnostic
      precision and might be instructive to treatment.

PMID- 29224315
TI  - [Identification of a novel ANKI gene mutation in hereditary spherocytosis].

PMID- 29224316
TI  - [Effects of NPM1 gene expression on acute myeloid leukemia cell lines and its
      mechanism].
AB  - Objective: To investigate the impact and mechanism of NPM1 gene expression on
      acute myeloid leukemia (AML) cell lines. Methods: Human AML cell line U937 and HL
      60 cells were transfected with NPM1 plasmid to establish stable clones, and the
      high NPM1 protein expression (NPM1(hi)) clones were screened by Western blot. The
      cell proliferation was assayed by methylthiazolyl tetrazolium bromide (MTT) ,
      cell cycle and cell apoptosis by flow cytometric, cell colony formation by
      microscope count, the molecular pathways related to cell cycle by Western blot.
      The expression of NPM1 gene in primary AML bone marrow mononuclear cells (BMMC)
      was investigated by RQ-PCR. Results: 1The proliferation of NPM1(hi) U937 and HL
      60 cells was similar with that of control cells (4.68+/-1.28 vs 3.89+/-0.81,
      3.34+/-0.37 vs 2.68+/-0.29, P>0.05) . 2The percentage of S phase in NPM1(hi) U937
      and HL-60 cells was higher than that in control cells[ (50.22+/-3.42) % vs
      (39.78+/-3.80) %, (59.01+/-3.27) % vs (43.94+/-2.08) %, P<0.05]. 3The anti
      apoptosis capacity and colony formation abilities of NPM1(hi) U937 cells
      increased than that of control cells[ (68.8+/-10.2) % vs (48.7+/-3.22) %, and
      (772.7+/-24.0) vs (652.3+/-16.5) , P<0.05], but the above abilities of NPM1(hi)
      HL60 cells were similar with that of control cells. 4 The expressions of CDK4,
      Cyclin D1, Cyclin D2 and Cyclin E in NPM1(hi) leukemia cells were higher than
      that of control cells, but the expression of Cyclin D3 was lower. 5The NPM1
      expression levels in AML patients with favorable cytogenetic prognosis were lower
      than that of patients with intermediate prognosis. Conclusions: NPM1 protein
      could promote more cells to enter S phase, enhance the ability of antiapoptosis
      and colony formation in AML cell lines. The quantitative level of NPM1 may
      predict the cytogenetic risk of AML patients.

PMID- 29224317
TI  - [A multicenter, retrospective study of pathogenic bacteria distribution and drug
      resistance in febrile neutropenic patients with hematological diseases in
      Shanghai].
AB  - Objective: To investigate the pathogen spectrum distribution and drug resistance
      of febrile neutropenic patients with hematological diseases in Shanghai. Methods:
      A retrospective study was conducted on the clinical isolates from the febrile
      neutropenic patients hospitalized in the departments of hematology in 12 general
      hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility
      test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to
      analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1
      260 clinical isolates were collected from the febrile neutropenic patients. Gram
      positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for
      66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) ,
      Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii
      (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked
      in the first 7 of all pathogens. In the respiratory tract secretions specimens,
      non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted
      for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for
      42.3% (104/246) and 32.6% (85/246) respectively in blood samples.
      Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and
      28.5% (55/193) respectively in pus specimens. The detection rates of methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase
      negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus
      bacterial strain was not found to be resistant to linezolid, vancomycin and
      teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was
      8.9%. Enterococcus was not detected resistance to oxazolidinone strains.
      Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance
      rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%,
      respectively. Stenotrophomonas maltophilia was more sensitive to minocycline
      hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of
      Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The
      antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas
      maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common
      antibiotics was lower than that of the CHINET surveillance. Conclusions: The
      pathogenic strain distribution in common infection sites of febrile neutropenic
      patients was characterized. Bacterial resistance surveillance was better than the
      CHINET nationwide large sample surveillance in China.

PMID- 29224318
TI  - [Distribution and drug resistance of pathogens of blood stream infection in
      patients with hematological malignancies after chemotherapy].
AB  - Objective: To investigate the distribution and resistance of pathogens isolated
      from blood cultures in patients with hematological malignancies after
      chemotherapy in Union Hospital of Fujian Medical University so as to understand
      the real situation of blood stream infection (BSI) and provide the basis for
      rational use of antibiotics in clinic. Methods: The data of 657 strains isolated
      from blood culture specimens of patients with hematological malignancies from
      January 2013 to December 2016 were collected analyzed. Results: A total of 657
      cases of blood culture positive bacterial strains were included in the study,
      involving 410 cases (62.4%) with single Gram-negative bacteria (G(-) bacteria) ,
      163 cases (24.8%) with single Gram-positive bacteria (G(+) bacteria) , 50 cases
      (7.6%) with single fungi. The most common 5 isolates in blood culture were
      Klebsiella pneumoniae (17.5%) , Escherichia coli (17.2%) , Coagulase negative
      staphylococci (CNS) (14.9%) , Pseudomonas aeruginosa (14.2%) and Staphylococcus
      aureus (3.5%) . The extended-spectrum beta-lactamase (ESBL) production rates of
      Klebsiella pneumoniae and Escherichia coli were 25.2% and 55.8%, respectively.
      ESBL producing strains were almost more resistant than non-ESBL producing
      strains. The resistance rates of Enterobacteriaceae to carbapenems,
      piperacillin/tazobactam and tigecycline were lower than 14.0%. The resistance
      rates of Pseudomonas aeruginosa to a variety of drugs were lower than 12.0%.
      Tigecycline-resistant Acinetobacter baumannii bacteria were not detected, and the
      resistance rates of Acinetobacter baumannii to cefixime and cefotaxime were 7.1%.
      Methicillin-resistant strains in CNS (MRCNS) and in Staphylococcus aureus (MRSA)
      accounted for 84.7% and 43.5%, respectively. Vancomycin, linezolid and
      tigecycline-resistant G(+) bacteria were not detected. Conclusion: The pathogens
      isolated from blood culture were widely distributed. Most of them were G(-)
      bacteria, and the resistance to antibiotics was quite common. Furhermore,
      vancomycin, linezolid and tigecycline can be chosen empirically to treat patiens
      who ar suspected to have G(+) bacterial BSI.

PMID- 29224319
TI  - [Screening of adult Ph-like acute lymphoblastic leukemia by multiplex real-time
      quantitative PCR].
AB  - Objective: To investigate the feasibility of multiplex real-time RT-PCR with
      fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia
      (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult
      B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in
      this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion
      gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients.
      The clinical features, treatment response and prognosis were analyzed in Ph-like
      fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58
      patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes
      positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were
      statistical differences in age, WBC count, immunophenotypes, cytogenetics and
      risk stratification among Ph-like fusion gene positive or CRLF2 over-expression
      patients, Ph(+) patients, MLL(+) patients and B-other patients. The 2-year
      overall survival rates were 65%, 47%, 64% and 74% respectively among these four
      groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and
      70% respectively among these four groups (P=0.010) . Conclusion: Routine
      screening of Ph-like ALL by multiplex RTPCR is feasible.

PMID- 29224321
TI  - [Acute myeloid leukemia treated with chidamide combined regimens: two cases
      report].

PMID- 29224320
TI  - [Comparative study of cytogenetic response evaluated by conventional banding
      analysis and fluorescence in situ hybridization in chronic myeloid leukemia
      patients during tyrosine kinase inhibitor treatment].
AB  - Objective: To compare the cytogenetic response detected by conventional banding
      analysis (CBA) and fluorescence in situ hybridization (FISH) and to explore the
      correlation between the cytogenetic and molecular response in chronic myeloid
      leukemia (CML) patients during tyrosine kinase inhibitor (TKI) treatment.
      Methods: CBA, FISH and real-time quantitative reverse transcriptase polymerase
      chain reaction (RQ-PCR) methods were performed to detect the cytogenetic and
      molecular response simultaneously in 504 bone marrow samples from 367 CML
      patients who received TKI treatment. Results: Among 504 samples, 344 were
      detected to reach complete cytogenetic response (CCyR) by CBA, while 297 samples
      reached CCyR by FISH which were considered to carry BCR-ABL positive cells<1%.
      When the results of CBA, FISH and RQ-PCR were compared in 493 samples at the same
      time, it showed that in 337 samples with CBA-CCyR, 273 (81.0%) reached FISH-CCyR
      and 289 (85.8%) were BCR-ABL(IS) (International Scale, IS) <=1% by RQ-PCR,
      compared to 9.0 (261/290) were BCR-ABL(IS) <=1% among 290 samples with FISH-CCyR.
      There was no significant difference in the median value of BCR-ABL(IS) between
      samples in CBA-CCyR and FISH-CCyR (0.21% vs 0.13%, z=-1.875, P=0.061) .
      Furthermore, when the samples were divided into three groups according to BCR-ABL
      positive cells (0,>0~<1%, 1%~5%) by FISH, the statistical difference was
      observed, the proportion of samples with BCR-ABL(IS) <=1% in the three groups
      were 94.1%, 57.6% and 27.7% respectively (chi(2)=43.499, P<0.001; chi(2)=9.734,
      P=0.003) , while the median value of BCR-ABL(IS) were 0.10%, 0.64% and 1.80%
      respectively (z=-5.864, P<0.001; z=-4.787, P<0.001) . Conclusion: FISH results
      were in good concordance with CBA in identify samples in CCyR, FISH was more
      sensitive and had better correlation with RQ-PCR results than CBA, but how to
      define FISH-CCyR need further study.

PMID- 29224322
TI  - [alpha1-antitrypsin Pittsburg mutations: report of two cases in the same family].
AB  - Objective: To analyze the clinical and laboratory abnormalities of two patients
      with alpha1-antitrypsin (alpha1-AT) Pittsburgh in a family and review the
      literatures. Methods: Both plasma clotting time and factor activities were
      performed using clotting or substrate methods. Platelet aggregation was evaluated
      using an optical aggregometer. The serum protein electrophoresis was performed on
      Sebia HYDRASYS by using Agarose gel. The exons of alpha1-AT were amplified by
      using polymerase chain reaction (PCR) and then sequenced and compared with NCBI
      GenBank records. Results: The proband had several ruptures of corpus luteum and
      bleeding after operation, while her daughter had no bleeding history. Both of
      them showed prolonged coagulation tests which could not be corrected by mixing
      with the normal plasma. They also showed low levels of plasma coagulation
      factors, undetected protein C and S activity and abnormal bands of alpha1
      globulin. The results of gene sequencing demonstrated that they were heterozygous
      for g.T17132G (p.Met358Arg) mutation of alpha1-antitrypsin gene (NG_008290.1) .
      Conclusions: Comparing with the data of previously reported cases, our results
      confirmed the obvious abnormality of coagulation test and the discrepancy of
      bleeding tendency of alpha1-antitrypsin Pittsburgh patients, and suggested that
      the rupture of corpus luteum would be a specific characteristic in women of child
      bearing age.

PMID- 29224323
TI  - [Effects of ICAT silencing in Wnt signaling pathway and NSC67657 induced cell
      differentiation of HL-60 cells].
AB  - Objectives: To investigate the effect of beta-catenin interacting protein 1
      (ICAT) silence in Wnt signaling pathway and sterol drug NSC67657 induced cell
      differentiation of HL60 cell. Methods: HL-60 cells were treated with NSC67657,
      the cell surface antigen CD14 expression was detected by flow cytometry.
      Lentivirus LV-ICAT-RNAi vector was constructed and infected HL-60 cells. Then the
      ICAT gene and protein expression were analyzed using real-time qPCR and Western
      blot technique. Furthermore, Co-immunoprecipitation assay was used to confirm the
      interaction of beta-catenin/ICAT proteins, and Western blot was employed to
      compare the expressions of Wnt signaling pathway downstream targets Cyclin D1,
      TCF-1 and c-Jun between Lentivirus LV-ICAT-RNAi vector infected HL-60 (HL-60i)
      cells and un-infected HL-60 (HL-60v) cells. The cellular differentiation of HL
      60i and HL-60v cells treated with NSC67657 for 24 h was evaluated by Wright's
      staining, transmission electron microscopy and flow cytometry analysis. Results:
      HL-60 cells could be induced to differentiate into monocytes by 10 MUmol/L
      NSC67657. The CD14 positive cells could reach to (92.30+/-5.14) % after NSC67657
      treatment for 5d. The co- immunoprecipitation assay demonstrated that ICAT
      protein did interact with beta-catenin protein, and the absorbance of protein
      electrophoresis bands increased in differentiated cells. The expressions of Wnt
      signaling pathway downstream target proteins in HL-60i cells were higher than
      that in HL-60v cells when they were treated by 10 MUmol/L NSC67657, but lower
      than NSC67657 untreated cells. CD14 positive HL-60i cells were significantly
      lower than that of HL-60v cells[ (8.33+/-3.14) % vs (19.08+/-4.73) %]when treated
      with NSC67657, but still higher than that of uninfected and untreated HL60 cells[
      (0.60+/-0.03) %] (F=119.24, P=0.010) . The results of cellular morphology and
      ultrastructure observation were also in accord with that of cell surface antigen
      analysis. Conclusions: ICAT does participate in HL-60 cells monocytic
      differentiation induced by NSC67657, and Wnt/beta-catenin signaling pathway might
      play a bridge role.

PMID- 29224324
TI  - [Clinical analysis of lung transplantation in eight patients with obstructive
      bronchiolitis syndrome after hematopoietic stem cell transplantation].
AB  - Objective: To investigate the efficacy and prognosis of lung transplantation (LT)
      for end-stage bronchiolitis obliterans syndrome (BOS) after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data
      of eight cases with end-stage BOS after allo-HSCT who were treated by LT in our
      hospital were retrospectively analyzed. Results: Eight patients with
      hematological malignancy underwent allo-HSCT, and the median age was 23 (12-40)
      years. The donors are parents or siblings. Severe BOS occurred in 8 patients
      after allo-HSCT, the median age for LT was 27.5 (13-47) years. The median
      interval between allo-HSCT and LT was 69 (21-132) months. The median follow-up
      time for 8 patients after LT was 15 (6-63) months, 7 patients survived, 1 patient
      died of pulmonary hemorrhage 15 months after LT treatment. Of the survivors,
      three had BOS again, and one of them received reduplicated lung transplantation.
      Conclusion: LT is an effective treatment for patients with severe BOS after HSCT.

PMID- 29224325
TI  - [Clinical analysis of 32 patients with acquired pure red cell aplasia].

PMID- 29224326
TI  - [Analysis of the gene in a hereditary coagulation factor VII deficiency
      pedigree].

PMID- 29224327
TI  - [Umbilical cord blood transplantation in the treatment of Chediak-Higashi
      syndrome with hemophagocytic syndrome: a case report and literature review].

PMID- 29224328
TI  - [Clinical characteristics and prognostic analysis of monoclonal IgM-related AL
      amyloidosis].

PMID- 29224330
TI  - [Mechanisms and management of thrombosis and bleeding in antiphospholipid
      syndrome].

PMID- 29224329
TI  - [Allogeneic hematopoietic stem cell transplantation for the treatment of severe
      aplastic anemia complicated with hepatocellular carcinoma: a case report and
      literature review].

PMID- 29224331
TI  - [Long non-coding RNA and lymphoma].

PMID- 29224333
TI  - Ferroelectricity and Piezoelectricity in Free-Standing Polycrystalline Films of
      Plastic Crystals.
AB  - Plastic crystals represent a unique compound class that is often encountered in
      molecules with globular structures. The highly symmetric cubic crystal structure
      of plastic crystals endows these materials with multiaxial ferroelectricity that
      allows a three-dimensional realignment of the polarization axes of the crystals,
      which cannot be achieved using conventional molecular ferroelectric crystals with
      low crystal symmetry. In this work, we focused our attention on malleability as
      another characteristic feature of plastic crystals. We have synthesized the new
      plastic/ferroelectric ionic crystals tetramethylammonium tetrachloroferrate(III)
      and tetramethylammonium bromotrichloroferrate(III), and discovered that free
      standing translucent films can be easily prepared by pressing powdered samples of
      these compounds. The thus obtained polycrystalline films exhibit ferroelectric
      polarization switching and a relatively large piezoelectric response at room
      temperature. The ready availability of functional films demonstrates the
      practical utility of such plastic/ferroelectric crystals, and considering the
      vast variety of possible constituent cations and anions, a wide range of
      applications should be expected for these unique and attractive functional
      materials.

PMID- 29224332
TI  - Statistical Coupling Analysis-Guided Library Design for the Discovery of Mutant
      Luciferases.
AB  - Directed evolution has proven to be an invaluable tool for protein engineering;
      however, there is still a need for developing new approaches to continue to
      improve the efficiency and efficacy of these methods. Here, we demonstrate a new
      method for library design that applies a previously developed bioinformatic
      method, Statistical Coupling Analysis (SCA). SCA uses homologous enzymes to
      identify amino acid positions that are mutable and functionally important and
      engage in synergistic interactions between amino acids. We use SCA to guide a
      library of the protein luciferase and demonstrate that, in a single round of
      selection, we can identify luciferase mutants with several valuable properties.
      Specifically, we identify luciferase mutants that possess both red-shifted
      emission spectra and improved stability relative to those of the wild-type
      enzyme. We also identify luciferase mutants that possess a >50-fold change in
      specificity for modified luciferins. To understand the mutational origin of these
      improved mutants, we demonstrate the role of mutations at N229, S239, and G246 in
      altered function. These studies show that SCA can be used to guide library design
      and rapidly identify synergistic amino acid mutations from a small library.

PMID- 29224334
TI  - Nitrogen-Deficient Graphitic Carbon Nitride with Enhanced Performance for Lithium
      Ion Battery Anodes.
AB  - Graphitic carbon nitride (g-C3N4) behaving as a layered feature with graphite was
      indexed as a high-content nitrogen-doping carbon material, attracting increasing
      attention for application in energy storage devices. However, poor conductivity
      and resulting serious irreversible capacity loss were pronounced for g-C3N4
      material due to its high nitrogen content. In this work, magnesiothermic
      denitriding technology is demonstrated to reduce the nitrogen content of g-C3N4
      (especially graphitic nitrogen) for enhanced lithium storage properties as
      lithium ion battery anodes. The obtained nitrogen-deficient g-C3N4 (ND-g-C3N4)
      exhibits a thinner and more porous structure composed of an abundance of
      relatively low nitrogen doping wrinkled graphene nanosheets. A highly reversible
      lithium storage capacity of 2753 mAh/g was obtained after the 300th cycle with an
      enhanced cycling stability and rate capability. The presented nitrogen-deficient
      g-C3N4 with outstanding electrochemical performances may unambiguously promote
      the application of g-C3N4 materials in energy-storage devices.

PMID- 29224335
TI  - Structure-Activity Relationship (SAR) of Phenolics for 2-Amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) Formation in Phenylalanine/Creatinine
      Reaction Mixtures Including (or Not) Oxygen and Lipid Hydroperoxides.
AB  - Phenolics can act as either promoters or inhibitors in 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) formation. In an attempt to clarify the
      structure-activity relationship (SAR) of phenolics for this reaction, the
      formation of PhIP in mixtures of phenylalanine, creatinine, 13-hydroperoxide of
      linoleic acid (LOOH) or 4-oxo-2-nonenal, and a wide array of phenolics was
      studied in the presence and in the absence of oxygen. The obtained results
      suggested that those phenolics having a high carbonyl scavenging ability
      inhibited the formation of PhIP. On the other hand, those phenolics that mainly
      acted as free radical scavengers and, therefore, were easily converted into
      quinones promoted the formation of PhIP. Phenolics of the first type were m
      diphenols and 1,3,5-triphenols. Phenolics of the second type were o- and p
      diphenols. Other phenolics, like 1,2,3- and 1,2,4-triphenols, exhibited a
      behavior either as carbonyl scavengers or as free radical scavengers depending on
      ring substitutions. Among the studied derivatives, the presence of a carboxylic
      or a methoxyl group at certain positions inhibited their behavior as carbonyl
      scavengers and, therefore, promoted the formation of PhIP. A procedure to
      classify phenolics as either carbonyl or free radical scavengers is proposed.

PMID- 29224336
TI  - Chemical Imprinting of Crystalline Silicon with Catalytic Metal Stamp in Etch
      Bath.
AB  - Conventional lithography using photons and electrons continues to evolve to scale
      down three-dimensional nanoscale patterns, but the complexity of technology and
      equipment is increasing due to diffraction and scattering problems. Physical
      contact lithography methods, such as nanoimprint and soft lithography, have been
      developed as an alternative technique. These techniques imprint predefined
      structures on a stamp to the polymer resist and use the polymer resist as a mask
      to dry etch the nanostructure on the substrate. In this study, we introduce a
      method of chemically imprinting crystalline silicon (Si) with a catalytic stamp
      to enable the direct etching of the Si without using a polymer mask. A metal
      catalyst is deposited on the predefined structure of the stamp. The stamp
      physically contacts the Si in the etching bath, and metal-assisted chemical
      etching occurs on the semiconductor surface. Since the metal catalyst is mounted
      on a stamp, it can be used repeatedly. This is a technology that combines
      conventional lithography and etching without using a polymer resist. This
      technology not only produced nano/microscale arrays of circular and square holes
      and trench structures but also successfully produced complex eagle-shaped
      structures that contained such structures.

PMID- 29224337
TI  - Spermidine-Activated Satellite Cells Are Associated with Hypoacetylation in
      ACVR2B and Smad3 Binding to Myogenic Genes in Mice.
AB  - Spermidine is an acetyltransferase inhibitor and a specific inducer of autophagy.
      Recently, spermidine is identified as a potential therapeutic agent for age
      related muscle atrophy and inherited myopathies. However, the effect of
      spermidine on nonpathological skeletal muscle remains unclear. In this study,
      long-term spermidine administration in mice lowered the mean cross-sectional area
      of the gastrocnemius muscle and reduced the expression of myosin heavy chain
      isoforms in the muscle, which was associated with ubiquitination. Moreover,
      spermidine supplementation induced autophagy in satellite cells and enhanced
      satellite cell proliferation. ChIP assay revealed that spermidine repressed
      H3K56ac in the promoter of ACVR2B and lowered the binding affinity of Smad3 to
      the promoters of Myf5 and MyoD. Altogether, our results indicate that long-term
      administration of spermidine can activate satellite cells, as well as enhance
      autophagy, eventually resulting in muscle atrophy. In addition, H3K56ac and Smad3
      emerged as key determinants of satellite cell activation.

PMID- 29224338
TI  - Dynamic Behavior of Rh Species in Rh/Al2O3 Model Catalyst during Three-Way
      Catalytic Reaction: An Operando X-ray Absorption Spectroscopy Study.
AB  - The dynamic behavior of Rh species in 1 wt% Rh/Al2O3 catalyst during the three
      way catalytic reaction was examined using a micro gas chromatograph, a NOx meter,
      a quadrupole mass spectrometer, and time-resolved quick X-ray absorption
      spectroscopy (XAS) measurements at a public beamline for XAS, BL01B1 at SPring-8,
      operando. The combined data suggest different surface rearrangement behavior,
      random reduction processes, and autocatalytic oxidation processes of Rh species
      when the gas is switched from a reductive to an oxidative atmosphere and vice
      versa. This study demonstrates an implementation of a powerful operando XAS
      system for heterogeneous catalytic reactions and its importance for understanding
      the dynamic behavior of active metal species of catalysts.

PMID- 29224339
TI  - Immobilization of Aluminum Hydroxide Particles on Quartz Crystal Microbalance
      Sensors to Elucidate Antigen-Adjuvant Interaction Mechanisms in Vaccines.
AB  - Aluminum hydroxide (AH) salts are the most widely used adjuvants in vaccine
      formulation. They trigger immunogenicity from antigenic subunits that would
      otherwise suffer from a lack of efficiency. Previous studies focusing on antigen
      AH interaction mechanisms, performed with model proteins, suggested that
      electrostatic interactions and phosphate-hydroxyl ligand exchanges drive protein
      adsorption on AH. We however recently evidenced that NaCl, used in vaccine
      formulation, provokes AH particle aggregation. This must be taken into account to
      interpret data related to protein adsorption on AH. Here, we report on the
      successful development and use of a stable AH-coated surface to explore the
      mechanisms of protein adsorption by means of ultrasensitive surface analysis
      tools. Bovine serum albumin (BSA) adsorption was studied at different pHs and
      ionic strengths (I) using quartz crystal microbalance. The results show that
      protein adsorption on the AH adjuvant cannot be explained solely by electrostatic
      interactions and ligand exchanges. Hence, a higher adsorption was observed at pH
      3 compared to pH 7, although AH and BSA respectively undergo repulsive and
      attractive electrostatic interactions at these pH values. Almost no effect of I
      on adsorption was moreover noted at pH 7. These new developments and observations
      not only suggest that other mechanisms govern protein adsorption on AH but also
      offer a new platform for the study of antigen adsorption in the context of
      vaccine formulation. Immobilizing particles on QCM sensors also enriches the
      range of applications for which QCM can be exploited, especially in colloid
      science.

PMID- 29224340
TI  - Atomic-Scale Influence of Grain Boundaries on Li-Ion Conduction in Solid
      Electrolytes for All-Solid-State Batteries.
AB  - Solid electrolytes are generating considerable interest for all-solid-state Li
      ion batteries to address safety and performance issues. Grain boundaries have a
      significant influence on solid electrolytes and are key hurdles that must be
      overcome for their successful application. However, grain boundary effects on
      ionic transport are not fully understood, especially at the atomic scale. The Li
      rich anti-perovskite Li3OCl is a promising solid electrolyte, although there is
      debate concerning the precise Li-ion migration barriers and conductivity. Using
      Li3OCl as a model polycrystalline electrolyte, we apply large-scale molecular
      dynamics simulations to analyze the ionic transport at stable grain boundaries.
      Our results predict high concentrations of grain boundaries and clearly show that
      Li-ion conductivity is severely hindered through the grain boundaries. The
      activation energies for Li-ion conduction traversing the grain boundaries are
      consistently higher than that of the bulk crystal, confirming the high grain
      boundary resistance in this material. Using our results, we propose a
      polycrystalline model to quantify the impact of grain boundaries on conductivity
      as a function of grain size. Such insights provide valuable fundamental
      understanding of the role of grain boundaries and how tailoring the
      microstructure can lead to the optimization of new high-performance solid
      electrolytes.

PMID- 29224341
TI  - Iron-Mediated Synthesis of Isoxazoles from Alkynes: Using Iron(III) Nitrate as a
      Nitration and Cyclization Reagent.
AB  - A simple and direct method for the iron(III) nitrate-mediated synthesis of
      isoxazoles from alkynes has been developed; both self-coupling and cross-coupling
      products could be successfully prepared from alkynes. Meanwhile, for the cross
      coupling and cyclizing of two different alkynes examined, the iron-mediated
      system shows a good chemoselectivity for the synthesis of corresponding
      isoxazoles. In our method, cheap and eco-friendly iron(III) nitrate is used as
      the nitration and cyclization reagent, and KI is used as the additive; they both
      play a positive role in this transformation. Furthermore, a different mechanism
      for the formation of isoxazoles from alkynes has been proposed.

PMID- 29224342
TI  - Lycosides, Unusual Carotenoid-Derived Terpenoid Glycosides from a Vegetable
      Juice, Inhibit Asexual Reproduction of the Plant Pathogen Phytophthora.
AB  - Vegetable juices, typical culture media for the plant pathogen Phytophthora,
      effectively induce its asexual reproduction (zoosporangia formation). However,
      some chromatographic fractions from a vegetable juice were found to inhibit
      asexual reproduction. Bioassay-guided chromatographic steps led to the isolation
      of four novel compounds, named lycosides A-D, 1-4, that could be metabolic
      products from a carotenoid. They showed 50% inhibitory activity against the
      asexual reproduction of P. capsici at 2.1-7.6 MUM. The structure-activity
      relationship and the universality of the inhibitory activity within the
      Phytophthora genus were also investigated. In addition, the quantitative analysis
      of lycosides in fresh vegetables and vegetable juices revealed that tomato is the
      source of these active substances. These food-derived chemicals could help
      provide safe agents to control the outbreak of the agricultural pest Phytophthora
      in fields.

PMID- 29224343
TI  - The Molecular Mechanism of Nanodroplet Stability.
AB  - Mixtures of nano- and microscopic oil droplets in water have recently been
      rediscovered as miniature reaction vessels in microfluidic environments and are
      important constituents of many environmental systems, food, personal care, and
      medical products. The oil nanodroplet/water interface stabilized by surfactants
      determines the physicochemical properties of the droplets. Surfactants are
      thought to stabilize nanodroplets by forming densely packed monolayers that
      shield the oil phase from the water. This idea has been inferred from droplet
      stability measurements in combination with molecular structural data obtained
      from extended planar interfaces. Here, we present a molecular level investigation
      of the surface structure and stability of nanodroplets and show that the surface
      structure of nanodroplets is significantly different from that of extended planar
      interfaces. Charged surfactants form monolayers that are more than 1 order of
      magnitude more dilute than geometrically packed ones, and there is no
      experimental correlation between stability and surfactant surface density.
      Moreover, dilute negatively charged surfactant monolayers produce more stable
      nanodroplets than dilute positively charged and dense geometrically packed
      neutral surfactant monolayers. Droplet stability is found to depend on the
      relative cooperativity between charge-charge, charge-dipole, and hydrogen-bonding
      interactions. The difference between extended planar interfaces and nanoscale
      interfaces stems from a difference in the thermally averaged total charge-charge
      interactions in the two systems. Low dielectric oil droplets with a size smaller
      than the Debye length in oil permit repulsive interactions between like charges
      from opposing interfaces in small droplets. This behavior is generic and extends
      up to the micrometer length scale.

PMID- 29224344
TI  - Hydrogen Shifts in Aryl Radicals and Diradicals: The Role of m-Benzynes.
AB  - Density functional and coupled cluster results are presented for hydrogen shifts
      in radicals derived from polycyclic aromatic hydrocarbons (PAHs) and for
      rearrangement mechanisms for several phenylenes. RCCSD(T)/cc-pVDZ//UBLYP/cc-pVDZ
      free energy barriers for 1,4-H shifts at 298 K are consistently predicted to be
      ca. 25 kcal/mol, whereas barriers for 1,5- and 1,6-shifts range from 6 to 28
      kcal/mol. The barriers correlate reasonably well with the distance from the
      radical center to the shifting hydrogen in the reactant. Proposed mechanisms (via
      diradical intermediates) of known rearrangements of linear [3]phenylene,
      benzo[b]biphenylene, and angular [4]phenylene have BD(T)/cc-pVDZ//(U)BLYP/cc-pVDZ
      computed barriers of 74-82 kcal/mol, consistent with pyrolysis temperatures of
      900 to 1100  degrees C. Hydrogen shift reactions in most of the aryl diradicals
      arising from phenylenes produce m-benzyne intermediates which, despite being 8-15
      kcal/mol more stable than other diradicals involved in the pathways, do not
      significantly lower the computed overall free energies of activation.

PMID- 29224345
TI  - NH Tautomerism of a Quadruply Fused Porphyrin: Rigid Fused Structure Delays the
      Proton Transfer.
AB  - We report herein NH tautomerism of a freebase derivative of a quadruply fused
      porphyrin (H2QFP-Mes, 3), which has one mesityl group at one of the beta
      positions of the nonfused pyrroles to lower the structural symmetry, allowing us
      to observe the NH tautomerism with 1H NMR spectroscopy. Compound 3 was revealed
      to have the two inner NH protons on the two nonfused pyrroles, and the NH
      tautomerism of 3 was evidenced by variable-temperature (VT) 1H NMR experiments in
      various deuterated solvents. The VT-NMR studies revealed that the activation
      barrier for the NH tautomerism of 3 was larger than that of tetraphenylporphyrin.
      The positive activation entropy (DeltaS? = 89 J mol-1 K-1), determined for the NH
      tautomerism, can be explained by dissociation of the pi-pi stacked dimer
      structure of 3 in the ground state, as evidenced by the crystal structure and NMR
      measurements. On the basis of the kinetic studies and density functional theory
      calculations, the stability of intermediates in the NH tautomerism of 3 and the
      transition states have been discussed in detail.

PMID- 29224346
TI  - Speciation of Mercury in Selected Areas of the Petroleum Value Chain.
AB  - Petroleum, natural gas, and natural gas condensate can contain low levels of
      mercury (Hg). The speciation of Hg can affect its behavior during processing,
      transport, and storage so efficient and safe management of Hg requires an
      understanding of its chemical form in oil, gas and byproducts. Here, X-ray
      absorption spectroscopy was used to determine the Hg speciation in samples of
      solid residues collected throughout the petroleum value chain including
      stabilized crude oil residues, sediments from separation tanks and condensate
      glycol dehydrators, distillation column pipe scale, and biosludge from wastewater
      treatment. In all samples except glycol dehydrators, metacinnabar (beta-HgS) was
      the primary form of Hg. Electron microscopy on particles from a crude sediment
      showed nanosized (<100 nm) particles forming larger aggregates, and confirmed the
      colocalization of Hg and sulfur. In sediments from glycol dehydrators, organic
      Hg(SR)2 accounted for ~60% of the Hg, with ~20% present as beta-HgS and/or
      Hg(SR)4 species. beta-HgS was the predominant Hg species in refinery biosludge
      and pipe scale samples. However, the balance of Hg species present in these
      samples depended on the nature of the crude oil being processed, i.e. sweet (low
      sulfur crudes) vs sour (higher sulfur crudes). This information on Hg speciation
      in the petroleum value chain will inform development of better engineering
      controls and management practices for Hg.

PMID- 29224347
TI  - Synthesis of Carbo[6]helicene Derivatives Grafted with Amino or Aminoester
      Substituents from Enantiopure [6]Helicenyl Boronates.
AB  - Enantiopure carbo[6]helicenyl boronates were synthesized using a photocyclization
      reaction as the key step. These compounds were further converted to various amino
      derivatives using copper-catalyzed azidation or amination and reductive
      alkylation of benzylazide by a helicenyl dichloroborane. Asymmetric Petasis
      condensation with glyoxylic acid and morpholine controlled by the helical
      chirality afforded the corresponding amino esters.

PMID- 29224348
TI  - Stereoselective Total Synthesis of Macrophage-Produced Prohealing 14,21-Dihydroxy
      Docosahexaenoic Acids.
AB  - Synthesis of 14S,21R- and 14S,21S-dihydroxy-DHA (diHDHA) among the four possible
      stereoisomers of 14,21-diHDHA was studied. Methyl (R)-lactate (>97% ee), selected
      as a C20-C22 fragment (DHA numbering), was converted to the C17-C22 phosphonium
      salt, which was subjected to a Wittig reaction with racemic C16-aldehyde of the
      C12-C16 part with the TMS and TBS-oxy groups at C12 and C14, yielding the C12-C22
      derivative with 14R/S and 21R chirality. Kinetic resolution using Sharpless
      asymmetric epoxidation of the TBS-deprotected allylic alcohol with l-(+)
      DIPT/Ti(O-i-Pr)4 afforded 14S-epoxy alcohol and 14R-allylic alcohol with >99%
      diastereomeric excess (de) for both. The CN group was introduced to the epoxy
      alcohol by reaction with Et2AlCN. The 14R-allylic alcohol was also converted to
      the nitrile via Mitsunobu inversion. Reduction of the nitrile with DIBAL afforded
      the key aldehyde corresponding to the C11-C22 moiety. The Wittig reaction of this
      aldehyde with a phosphonium salt of the remaining C1-C10 part followed by
      functional group manipulation gave 14S,21R-diHDHA. Similarly, ethyl (S)-lactate
      (>99% ee) was converted to 14S,21S-diHDHA. The chiral LC-UV-MS/MS analysis
      demonstrated that each of these two 14,21-diHDHAs synthesized using the presented
      total organic synthesis was highly stereoselective and identical to the
      macrophage-produced counterpart.

PMID- 29224349
TI  - Identification and Quantitation of the Bioactive Components in Osmanthus fragrans
      Fruits by HPLC-ESI-MS/MS.
AB  - Information on the chemical composition of Osmanthus fragrans fruits is still
      limited because there are many compounds present in low concentrations in the
      plant. In this work, the bioactive components in O. fragrans fruit extract were
      investigated by a new high-performance liquid chromatography electrospray
      ionization tandem mass spectrometry method, which allows sensitive analysis both
      in identification and quantitation. A total of 28 compounds were tentatively
      identified, and 16 components were discovered in O. fragrans fruits for the first
      time. The validated quantitative methods for the determination of the bioactive
      components were subsequently applied to analyze batches of O. fragrans fruits
      from different cultivars, which is beneficial for the comprehensive utilization
      of O. fragrans fruits.

PMID- 29224350
TI  - Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic
      Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic CuI
      Intermediates.
AB  - A series of experimental studies, along with DFT calculations, are reported that
      provide a detailed view into the mechanism of Ullmann coupling of phenols with
      aryl halides in the presence of catalysts generated from Cu(I) and bidentate,
      anionic ligands. These studies encompass catalysts containing anionic ligands
      formed by deprotonation of 8-hydroxyquinoline, 2-pyridylmethyl tert-butyl ketone,
      and 2,2,6,6-tetramethylheptane-3,5-dione. Three-coordinate, heteroleptic species
      [Cu(LX)OAr]- were shown by experiment and DFT calculations to be the most stable
      complexes in catalytic systems containing 8-hydroxyquinoline or 2-pyridylmethyl
      tert-butyl ketone and to be generated reversibly in the system containing 2,2,6,6
      tetramethylheptane-3,5-dione. These heteroleptic complexes were characterized by
      a combination of 19F NMR, 1H NMR, and UV-vis spectroscopy, as well as ESI-MS. The
      heteroleptic complexes generated in situ react with iodoarenes to form biaryl
      ethers in high yields without evidence for an aryl radical intermediate.
      Measurements of 13C/12C isotope effects showed that oxidative addition of the
      iodoarene occurs irreversibly. This information, in combination with the kinetic
      data, shows that oxidative addition occurs to the [Cu(LX)OAr]- complexes and is
      turnover-limiting. A Hammett analysis of the effect of phenoxide electronic
      properties on the rate of the reaction of [Cu(LX)OAr]- with iodotoluene also is
      consistent with oxidative addition of the iodoarene to an anionic phenoxide
      complex. Calculations by DFT suggest that this oxidative addition is followed by
      dissociation of I- and reductive elimination of the biaryl ether from the
      resulting neutral Cu(III) complex.

PMID- 29224351
TI  - Cellulose-Based Composite Macrogels from Cellulose Fiber and Cellulose Nanofiber
      as Intestine Delivery Vehicles for Probiotics.
AB  - Cellulose-based composite macrogels made by cellulose fiber/cellulose nanofiber
      (CCNM) were used as an intestine delivery vehicle for probiotics. Cellulose
      nanofiber (CNF) was prepared by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical
      (TEMPO)-mediated oxidation system, and the carboxyl groups in CNF acted as pore
      size and pH responsibility regulators in CCNMs to regulate the probiotics loading
      and controlled release property. The macrogel presented a porosity of 92.68% with
      a CNF content of 90%, and the corresponding released viable Lactobacillus
      plantarum (L. plantarum) was up to 2.68 * 108 cfu/mL. The porous structure and
      high porosity benefited L. plantarum cells to infiltrate into the core of
      macrogels. In addition, the macrogels made with high contents of CNF showed
      sustainable release of L. plantarum cells and delivered enough viable cells to
      the desired region of intestine tracts. The porous cellulose macrogels prepared
      by a green and environmental friendly method show potential in the application of
      fabricating targeted delivery vehicles of bioactive agents.

PMID- 29224353
TI  - Curcumin Protects against Atherosclerosis in Apolipoprotein E-Knockout Mice by
      Inhibiting Toll-like Receptor 4 Expression.
AB  - Toll-like receptor 4 (TLR4) has been reported to play a critical role in the
      pathogenesis of atherosclerosis, the current study aimed to investigate whether
      curcumin suppresses atherosclerosis development in ApoE-knockout (ApoE-/-) mice
      by inhibiting TLR4 expression. ApoE-/- mice were fed a high-fat diet supplemented
      with or without curcumin (0.1% w/w) for 16 weeks. Curcumin supplementation
      significantly reduced TLR4 expression and macrophage infiltration in
      atherosclerotic plaques. Curcumin also reduced aortic interleukin-1beta (IL
      1beta), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule
      1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression, nuclear
      factor-kappaB (NF-kappaB) activity, and plasma IL-1beta, TNF-alpha, soluble VCAM
      1 and ICAM-1 levels. In addition, aortic sinus sections revealed that curcumin
      treatment reduced the extent of atherosclerotic lesions and inhibited
      atherosclerosis development. In vitro, curcumin inhibited NF-kappaB activation in
      macrophages and reduced TLR4 expression induced by lipopolysaccharide. Our
      results indicate that curcumin protects against atherosclerosis at least
      partially by inhibiting TLR4 expression and its related inflammatory reaction.

PMID- 29224352
TI  - Functional Characterization of Human Peptide/Histidine Transporter 1 in Stably
      Transfected MDCK Cells.
AB  - The proton-coupled oligopeptide transporter PHT1 (SLC15A4), which facilitates
      cross-membrane transport of histidine and small peptides from inside the
      endosomes or lysosomes to cytosol, plays an important role in intracellular
      peptides homeostasis and innate immune responses. However, it remains a challenge
      to elucidate functional properties of the PHT1 transporter because of its
      subcellular localization. The purpose of this study was to resort hPHT1 protein
      from the subcellular to outer cell membrane of MDCK cells stably transfected with
      human PHT1 mutants, and to characterize its functional activity in these cells.
      Using this model, the functional activity of hPHT1 was evaluated by cellular
      uptake studies with d3-l-histidine, GlySar, and the bacterial peptidoglycan
      products MDP and Tri-DAP. We found that the disruption of two dileucine motifs
      was indispensable for hPHT1 transporter being preferentially targeting to plasma
      membranes. hPHT1 showed high affinity for d3-l-histidine and low affinity for
      GlySar, with Km values of 16.3 +/- 1.9 MUM and 1.60 +/- 0.30 mM, respectively.
      Moreover, the bacterial peptidoglycan components MDP and Tri-DAP were shown
      conclusively to be hPHT1 substrates. The uptake of MDP by hPHT1 was inhibited by
      di/tripeptides and peptide-like drugs, but not by glycine and acyclovir. The
      functional activity of hPHT1 was also pH-dependent, with an optimal cellular
      uptake in buffer pH 6.5. Taken together, we established a novel cell model to
      evaluate the function of hPHT1 in vitro, and confirmed that MDP and Tri-DAP were
      substrates of hPHT1. Our findings suggest that PHT1 may serve as a potential
      target for reducing the immune responses and for drug treatment of inflammatory
      diseases.

PMID- 29224354
TI  - High-Speed Counter-Current Chromatography (HSCCC) Purification of Antifungal
      Hydroxy Unsaturated Fatty Acids from Plant-Seed Oil and Lactobacillus Cultures.
AB  - Hydroxy unsaturated fatty acids (HUFA) can function as antifungal agents. To
      investigate the antifungal spectrum, that is, the scope of the in vitro fungal
      inhibition activities of HUFA and their potential applications, three HUFA were
      produced by microbial transformation or extracted from plant-seed oils; these
      compounds included coriolic acid (13-hydroxy-9,11-octadecadienoic acid) from
      Coriaria seed oil, 10-hydroxy-12-octadecenoic acid from cultures of Lactobacillus
      hammesii, and 13-hydroxy-9-octadecenoic acid from cultures of Lactobacillus
      plantarum TMW1.460Deltalah. HUFA were purified by high-speed counter-current
      chromatography (HSCCC), characterized by LC-MS and MS/MS, and their antifungal
      activities were evaluated with 15 indicator fungal strains. The HUFA had
      different antifungal spectra when compared with unsaturated fatty acids with
      comparable structures but without hydroxy groups. The inhibitory effects of HUFA
      specifically targeted filamentous fungi, including Aspergillus niger and
      Penicillium roqueforti, whereas yeasts, including Candida spp. and Saccharomyces
      spp., were resistant to HUFA. The findings here support the development of food
      applications for antifungal HUFA.

PMID- 29224356
TI  - Heating and Soaking Influence in Vitro Hindgut Fermentation of Tropical Legume
      Grains in Pigs.
AB  - The effects of different thermal (raw versus autoclaving or boiling for 5 and 20
      min) and soaking (with or without) treatments on the in vitro hindgut
      fermentation in pigs of undigested residue collected after in vitro foregut
      digestion of tropical legumes' grains (Canavalia brasiliensis; Lablab purpureus;
      pink, red and white Vigna unguiculata) were investigated. The undigested residue
      was fermented with a pig fecal inoculum to determine fermentability, gas, and
      short-chain fatty acid (SCFA) productions. Soaked raw legumes increased the
      production of SCFAs (e.g., butyric acid) and fermentability, while autoclaving
      reduced them. The productions of butyric acid and energy derived from SCFAs
      differed between legumes, with canavalia and lablab having the lowest and highest
      values, respectively. SCFAs and energy productions were highly related to the
      predicted nutrients entering the hindgut. In conclusion, different heating and
      soaking treatments can be applied to legumes to modulate the production of target
      SCFAs.

PMID- 29224355
TI  - Structural Features and Domain Movements Controlling Substrate Binding and
      Cofactor Specificity in Class II HMG-CoA Reductase.
AB  - The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the
      production of countless metabolites and natural products. Although inhibition of
      HMGR by statin drugs is well-understood, several mechanistic details of HMGR
      catalysis remain unresolved, and the structural basis for the wide range of
      cofactor specificity for either NADH or NADPH among HMGRs from different
      organisms is also unknown. Here, we present crystal structures of HMGR from
      Streptococcus pneumoniae (SpHMGR) alongside kinetic data of the enzyme's cofactor
      preferences. Our structure of SpHMGR bound with its kinetically preferred NADPH
      cofactor suggests how NADPH-specific binding and recognition are achieved. In
      addition, our structure of HMG-CoA-bound SpHMGR reveals large, previously unknown
      conformational domain movements that may control HMGR substrate binding and
      enable cofactor exchange without intermediate release during the catalytic cycle.
      Taken together, this work provides critical new insights into both the HMGR
      reaction mechanism and the structural basis of cofactor specificity.

PMID- 29224357
TI  - Investigation of the Nucleophilic Attack of Dichlorvos by Reduced Sulfur Species
      Using 1H NMR.
AB  - The mechanism of the reaction of dichlorvos through hydrolysis reactions and
      through the reaction with polysulfide (Sn2-) and thiophenolate (PhS-) was
      investigated by proton nuclear magnetic resonance (1H NMR). The study confirmed
      product identities of an organophosphorus insecticide reacting with reduced
      sulfur species using 1H NMR in oxygen sensitive solutions. The experiments of
      dichlorvos with polysulfide led to the detection of a previously undetected
      product. The thiophenolate experiments were further advanced to investigate
      second-order rate kinetics using an internal standard. The experiments provide
      new evidence for a nucleophilic attack by the reduced sulfur species at the
      methoxy carbon of dichlorvos. In addition, the observation of in situ reaction
      dynamics illustrates the applicability of 1H NMR spectroscopy toward kinetic
      investigations in environmental science.

PMID- 29224358
TI  - Extracellular versus Intracellular Degradation of Nanostructured Silica
      Particles.
AB  - Silica nanoparticles appear as promising drug carriers for intracellular
      delivery. However, the mechanisms by which they are degraded within cells remain
      largely unknown. In this context, we have prepared three types of PEGylated
      fluorescent silica nanoparticles with various internal structures (core-shell
      biocomposite, multilayered, and hollow mesoporous) and studied their degradation
      in a buffer, in a culture medium, and in contact with human dermal fibroblasts.
      All particles were prone to dissolve in solution, leading to an increase of
      porosity and/or the precipitation of new colloids and eventually fragmentation,
      with a faster rate in the medium compared to that in the buffer. All particles
      were also uptaken by the cells without significant cytotoxic effect. Their
      intracellular degradation occurred faster than in suspension, but following
      almost similar dissolution mechanisms. These results strongly suggest that in
      these conditions, silica nanoparticles must be primarily considered as
      hydrolytically degraded and not biodegraded, a point of importance for their
      future applications in drug delivery.

PMID- 29224361
TI  - Precision medicine strategies in oncology: mixed approaches to matched therapies.

PMID- 29224359
TI  - A Reduced Transcriptome Approach to Assess Environmental Toxicants Using
      Zebrafish Embryo Test.
AB  - Omics approaches can monitor responses and alterations of biological pathways at
      genome-scale, which are useful to predict potential adverse effects by
      environmental toxicants. However, high throughput application of transcriptomics
      in chemical assessment is limited due to the high cost and lack of "standardized"
      toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was
      developed to represent the whole transcriptome and to profile bioactivity of
      chemical and environmental mixtures in zebrafish embryo. RZT gene set of 1637
      zebrafish Entrez genes was designed to cover a wide range of biological
      processes, and to faithfully capture gene-level and pathway-level changes by
      toxicants compared with the whole transcriptome. Concentration-response modeling
      was used to calculate the effect concentrations (ECs) of DEGs and corresponding
      molecular pathways. To validate the RZT approach, quantitative analysis of gene
      expression by RNA-ampliseq technology was used to identify differentially
      expressed genes (DEGs) at 32 hpf following exposure to seven serial dilutions of
      reference chemical BPA (10-10E-5MUM) or each of four water samples ranging from
      wastewater to drinking water (relative enrichment factors 10-6.4 * 10-4). The RZT
      ampliseq-embryo approach was both sensitive and able to identify a wide spectrum
      of biological activities associated with BPA exposure. Water quality was
      benchmarked based on the sensitivity distribution curve of biological pathways
      detected using RZT-ampliseq-embryo. Finally, the most sensitive biological
      pathways were identified, including those linked with adverse reproductive
      outcomes, genotoxicity and development outcomes. RZT-ampliseq-embryo approach
      provides an efficient and cost-effective tool to prioritize toxicants based on
      responsiveness of biological pathways.

PMID- 29224360
TI  - Predicting Intelligibility Deficit in Dysphonic Speech with Cepstral Peak
      Prominence.
AB  - OBJECTIVES: The aim of this study was to examine the potential of cepstral peak
      prominence (CPP) for predicting the intelligibility deficit in dysphonic speech.
      METHODS: Sentences from Hearing-in-Noise Test were recorded from 18 speakers with
      dysphonia and 18 speakers with normal voice. These samples were presented to 60
      adults with normal hearing in quiet and noise at signal to noise ratio of +0 dB.
      Intelligibility was measured by orthographic transcription. Cepstral peak
      prominence was measured for all samples. Correlation between CPP and
      intelligibility score was examined. RESULTS: Intelligibility was significantly
      lower in dysphonic speech than normal speech in the presence of background noise.
      The correlation between CPP and intelligibility score was moderate when the
      intelligibility scores were averaged per speaker. CONCLUSIONS: Cepstral peak
      prominence only moderately predicts intelligibility deficit in dysphonic speech.
      Accordingly, CPP alone is not sufficient for describing the deficit.

PMID- 29224362
TI  - Structure determination and quantification of a new flavone glycoside with anti
      acetylcholinesterase activity from the herbs of Elsholtzia ciliata.
AB  - Three acacetin triglycosides (compounds 1, 2 and 3) were isolated from the herbs
      of Elsholtzia ciliata (Labiatae). The structure were identified as 7-O-beta-D
      glucopyranosyl-(1 -> 2)[alpha-L-rhamnopyranosyl-(1 -> 6)]-beta-D-glucopyranoside
      (compound 1), 7-O-(6-O-acetyl)-beta-D-glucopyranosyl-(1 -> 2)[alpha-L
      rhamnopyranosyl-(1 -> 6)]-beta-D-glucopyranoside (compound 2) and 7-O-(6-O
      acetyl)-beta-D-glucopyranosyl-(1 -> 2)[(4-O-acetyl)-alpha-L-rhamnopyranosyl-(1 ->
      6)]-beta-D-glucopyranoside (compound 3) of acacetin. The structures of these
      compounds were determined on the basis of 2D-NMR spectroscopic data. Compound 3
      has not been isolated from a natural source. In addition, the three compounds
      were quantitatively analysed by HPLC. Acetylcholinesterase (AChE) inhibition
      activity was assayed to find anti-Alzheimer's activity, since this enzyme
      increases the concentration of acetylcholine (ACh), a neurotransmitter,
      responsible for brain's memory. Acacetin, the aglycone of the three compounds,
      exhibited a potent anti-cholinesterase activity (IC50, 50.33 +/- 0.87), though
      its glycosides (1, 2 and 3) were less active. HPLC analysis demonstrated that the
      three compounds were contained in the MeOH extract in the order of compounds 2
      (12.63 mg/g extract) > 3 (3.10 mg/g) > 1 (2.92 mg/g).

PMID- 29224363
TI  - A new cadinane sesquiterpenoid from cultures of the Basidiomycete Panus
      conchatus.
AB  - A new cadinane sesquiterpenoid, named panutorulon A (1), was isolated from
      cultures of the basidiomycete Panus conchatus. The new structure was elucidated
      by means of spectroscopic methods. Compound 1 was tested for its cytotoxicity
      against five human cancer cell lines and for its inhibitory activity against
      isozymes of 11beta-hydroxysteroid dehydrogenases (11beta-HSD).

PMID- 29224364
TI  - New anticoagulants for venous thromboembolism and atrial fibrillation: what the
      future holds.
AB  - INTRODUCTION: The field of anticoagulation has seen impressive progress over the
      last decade. The introduction of the Non Vitamin K Oral Anticoagulants (NOACs)
      has revolutionized practice surrounding thromboprophylaxis, treatment of
      thromboembolic disease and stroke prevention in atrial fibrillation (AF).
      However, the search for the 'holy grail' of anticoagulation, an agent that
      combines optimal efficacy with minimal bleeding diathesis, continues. Areas
      covered: In this paper we aim to summarize the current evidence from pre-clinical
      studies and early phase clinical trials, presenting the pharmacodynamic and
      pharmacokinetic properties as well as the safety and efficacy profiles of the
      most important antithrombotic agents in development. Expert opinion: Research
      focused on the development of new anticoagulation agents is rapidly expanding.
      Although the exploration of antithrombotic agents that act on well-established
      targets such factor Xa and thrombin remains the mainstay, attention has also
      shifted to other factors in the coagulation cascade. The evidence emerging from
      clinical research is growing, generating exciting possibilities in the field of
      anticoagulation.

PMID- 29224365
TI  - Evaluation of genotoxic and modulatory effects of Nyctanthes arbor-tristis calyx
      extract and the isolated crocin in Ames' assay.
AB  - Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the
      traditional medicinal systems of several Asian countries. In the present study,
      potential genotoxicity and modulatory effects of ethanolic extract of NAT flower
      calyx (NAT FCE) and crocin, a carotenoid principle were evaluated employing
      standard Salmonella assay. Experiments evaluating the genotoxic potential of NAT
      FCE and crocin, with and without the S9-activation in TA 98, TA 100 and TA 102
      showed a lack of increase in revertant mutants. Evaluation of modulatory effects
      of NAT FCE and crocin, without the S9, showed significant decrease in the number
      of 4-nitro-o-phenylenediamine-, sodium azide- and ethyl methanesulfonate-induced
      revertants. However, with S9, NAT FCE and crocin moderately increased the 2
      aminoanthracene-induced revertants in TA 98; they moderately decreased revertants
      in TA 100 and TA 102. Both NAT FCE and crocin have been shown to be non-genotoxic
      and to be able to modulate responses of standard mutagens.

PMID- 29224366
TI  - Biotransformation of soy flour isoflavones by Aspergillus niger NRRL 3122 beta
      glucosidase enzyme.
AB  - beta-glucosidase enzyme produced from Aspergillus niger NRRL 3122 has been
      partially purified and characterised. Its molecular weight was 180 KDa. The
      optimal pH and temperature were 3.98 and 55  degrees C, respectively. It promoted
      the hydrolysis of soy flour isoflavone glycosides to their aglycone. Two-level
      Plackett-Burman design was applied and effective variables for genistein
      production were determined. Reaction time had a significant positive effect, and
      pH had a significant negative effect. They were further evaluated using Box
      Behnken model. Accordingly, the optimal combination of the major reaction
      affecting factors was reaction time, 5 h and pH, 4. The concentration of
      genistein increased by 11.73 folds using this optimal combination. The
      antioxidant activity of the non-biotransformed and biotransformed soy flour
      extracts was determined by DPPH method. It was found that biotransformation
      increased the antioxidant activity by four folds.

PMID- 29224367
TI  - Effect of ruxolitinib therapy on the quality-of-life of Japanese patients with
      myelofibrosis.
AB  - OBJECTIVES: Myelofibrosis (MF) is associated with a significant symptom burden
      that severely impacts patient quality-of-life (QoL). Ruxolitinib, a potent Janus
      kinase 1 (JAK1)/JAK2 inhibitor, led to substantial improvements in splenomegaly,
      MF-associated symptoms, and QoL in the phase 3 COMFORT studies, proving superior
      to placebo and best available therapy. This study evaluated the effect of
      ruxolitinib on symptoms and QoL in Japanese patients with MF. METHODS: A pooled
      analysis of studies A2202 (NCT01392443) and AJP01 (NCT02087059) of ruxolitinib in
      Japanese patients with MF (n = 81) was conducted. Changes in total symptom score
      (TSS) and the European Organisation for Research and Treatment of Cancer Quality
      of Life Questionnaire Core 30 were summarized. RESULTS: Most patients received a
      starting dose of 15 or 20 mg twice daily (BID) and had a final titrated dose of
      >=10 mg BID. Overall, 67.7% (44/65) achieved a >=50% reduction from baseline in
      TSS at week 24. Reductions in TSS were seen in every dose group; the greatest
      reductions occurred in patients with a final titrated dose of 20 or 25 mg BID.
      Improvements in QoL were seen in patients who achieved a >=50% reduction in TSS.
      Generally, improvements in TSS and individual symptoms correlated with reductions
      in spleen size, with those having a >=35% reduction in spleen volume having the
      greatest improvements. CONCLUSIONS: Consistent with COMFORT-I, ruxolitinib
      provided substantial improvements in symptoms and QoL in Japanese patients with
      MF, with higher doses of ruxolitinib associated with better responses.

PMID- 29224369
TI  - Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid
      derivatives.
AB  - A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was
      synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending
      alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at
      the end of the side chain. Their antiproliferative activities were evaluated in
      vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3).
      The results showed that all the target compounds exhibited antiproliferative
      activities against investigated cancer cells with IC50 values of 9.51-53.33 MUM.
      Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited
      more potency as compared to positive control cis-Platin.

PMID- 29224368
TI  - Immune response proteins as predictive biomarkers of doxorubicin-induced
      cardiotoxicity in breast cancer patients.
AB  - Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent
      cardiotoxicity. Currently, there are no specific biomarkers that can identify
      patients at risk during the initial doses of chemotherapy. The aim of this study
      was to examine plasma cytokines/chemokines and potential cardiovascular
      biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were
      collected before (T0), and after the first (T1) and the second (T2) cycles of DOX
      based chemotherapy of 27 breast cancer patients, including five patients who
      presented with >10% decline of left ventricular ejection fraction (LVEF), five
      patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF
      at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of
      treatment). Multiplex immunoassays were used to screen plasma samples for 40
      distinct chemokines, nine matrix metalloproteinases, 33 potential markers of
      cardiovascular diseases, and the fourth-generation cardiac troponin T assay. The
      results showed that the patients with abnormal decline of LVEF (>10%) had lower
      levels of CXCL6 and sICAM-1 and higher levels of CCL23 and CCL27 at T0; higher
      levels of CCL23 and lower levels of CXCL5, CCL26, CXCL6, GM-CSF, CXCL1, IFN
      gamma, IL-2, IL-8, CXCL11, CXCL9, CCL17, and CCL25 at T1; and higher levels of
      MIF and CCL23 at T2 than the patients who maintained normal LVEF. Patients with
      LVEF decline of 5-10% had lower plasma levels of CXCL1, CCL3, GDF-15, and
      haptoglobin at T0; lower levels of IL-16, FABP3, and myoglobin at T1; and lower
      levels of myoglobin and CCL23 at T2 as compared to the patients who maintained
      normal LVEF. This pilot study identified potential biomarkers that may help
      predict which patients are vulnerable to DOX-induced cardiotoxicity although
      further validation is needed in a larger cohort of patients. Impact statement
      Drug-induced cardiotoxicity is one of the major concerns in drug development and
      clinical practice. It is critical to detect potential cardiotoxicity early before
      onset of symptomatic cardiac dysfunction or heart failure. Currently there are no
      qualified clinical biomarkers for the prediction of cardiotoxicity caused by
      cancer treatment such as doxorubicin (DOX). By using multiplex immunoassays, we
      identified proteins with significantly changed plasma levels in a group of breast
      cancer patients who were treated with DOX-based chemotherapy and produced
      cardiotoxicity. These proteins were associated with immune response and were
      identified before DOX treatment or at early doses of treatment, thus they could
      be potential predictive biomarkers of cardiotoxicity although further validation
      is required to warrant their clinical values.

PMID- 29224370
TI  - Authenticating apple cider vinegar's home remedy claims: antibacterial,
      antifungal, antiviral properties and cytotoxicity aspect.
AB  - These are the days when one would go online first seeking home remedies before
      seeing a doctor. Apple cider vinegar (ACV) is one such popular yet scientifically
      under-validated remedy. Our results prove the unequivocal antimicrobial activity
      of ACV to be true at full strength concentrations. However, the activity cannot
      be generalised because although strong antibacterial activity was observed at 25%
      concentrations, in terms of antifungal activity, yeasts, especially Candida were
      found to be less susceptible. The antimicrobial/antioxidant properties are
      ascertained to the total phenolic contents of ACV, as confirmed by our
      characterisation of the bioactive compounds and antioxidant activity. When
      checking for its cytotoxicity, ACV exhibited toxicity even at concentrations as
      low as 0.7%. These results indicate that there is no question of generalising the
      idea of ACV usage, instead more in vitro and in vivo validations are necessary in
      order to precisely weigh the pros and cons of ACV.

PMID- 29224372
TI  - Do condensed tannins from Lysiloma latisiliquum have a role in its anthelmintic
      activity?
AB  - We would like to comment on a recent paper by Hernandez-Bolio et al. (2017, Nat.
      Prod. Res. DOI: 10.1080/14786419.2017.1317774) where an extract free of condensed
      tannin (CT) was evaluated and concluded that Lysiloma latisiliquum CT does not
      have a role in its anthelmintic (AH) activity. This letter discusses the AH
      potential of L. latisiliquum based on previously published evidence of a partial
      role of CT using different AH assays and Haemonchus contortus isolates. Because
      the experimental design employed in the above-mentioned paper did not allow a
      clear-cut conclusion regarding the role of CT, this suggests that a specific
      experiment must be designed to confirm or reject the involvement of CT
      fraction(s) on L. latisiliquum AH activity.

PMID- 29224371
TI  - Electrostatic interaction of tumor-targeting adenoviruses with aminoclay acquires
      enhanced infectivity to tumor cells inside the bladder and has better cytotoxic
      activity.
AB  - In a previous report, 3-aminopropyl functionalized magnesium phyllosilicate
      (aminoclay) improved adenovirus transduction efficiency by shielding the negative
      surface charges of adenovirus particles. The present study analyzed the
      physicochemical characterization of the electrostatic complex of adenoviruses
      with aminoclay and explored whether it could be utilized for enhancing tumor
      suppressive activity in the bladder. As a result of aminoclay-adenovirus
      nanobiohybridization, its transduction was enhanced in a dose-dependent manner,
      increasing transgene expression in bladder cancer cells and in in vivo animal
      models. Physicochemical studies demonstrated that positively charged aminoclay
      led to the neutralization of negative surface charges of adenoviruses, protection
      of adenoviruses from neutralizing antibodies and lowered transepithelial
      electrical resistance (TEER). As expected from the physicochemical properties,
      the aminoclay enabled tumor-targeting adenoviruses to be more potent in killing
      bladder cancer cells and suppressing tumor growth in orthotopic bladder tumors,
      suggesting that aminoclay would be an efficient, versatile and biocompatible
      delivery carrier for intravesical instillation of adenoviruses.

PMID- 29224373
TI  - Pharmacotherapy and treatment options for HIV-associated nephropathy.
AB  - INTRODUCTION: Human immunodeficiency virus (HIV) remains a worldwide disease with
      significant mortality and morbidity. There are a multitude of HIV-related kidney
      diseases including HIV-associated nephropathy (HIVAN) most prominently. The risk
      of developing HIVAN increases with decreasing CD4 count, higher viral load, and
      based on genetic factors. The mortality rate for those with HIVAN-end stage renal
      disease (ESRD) remains 2.5-3 times higher than ESRD patients without HIVAN. Areas
      covered: The epidemiology of HIVAN, particularly risk assessment, will be
      explored in this review. Further, the pathogenesis of HIVAN, from viral-specific
      renal expression to the role of genetics as well as characteristic renal
      pathology will be described. Diagnosis and management of HIVAN will be addressed,
      with an emphasis on various treatment strategies including medication, dialysis,
      and kidney transplantation. Expert opinion: HIVAN is associated with a high risk
      for progression to ESRD and increased mortality. The backbone of HIVAN therapy
      remains combined anti-retroviral therapy (cART), while adjunctive therapies
      including RAAS blockade and prednisone, should be considered. In those who
      progress to ESRD, dialysis remains the mainstay of management, though increasing
      evidence has demonstrated that kidney transplantation can be effective in those
      with controlled HIV disease.

PMID- 29224374
TI  - Chemical characterisation and hepatoprotective potential of Cosmos sulphureus
      Cav. and Cosmos bipinnatus Cav.
AB  - This study was conducted to validate the hepatoprotective activity of Cosmos
      sulphureus and Cosmos bipinnatus. Aqua-methanolic extracts of both plants were
      evaluated for the presence of various phyto-constituents through HPLC. Different
      doses of both plant extracts were administered to rats for nine days. Standard
      control was silymarin 100 mg/kg. Paracetamol 1 gm/kg was administered 3 h post
      treatment on 9th day for induction of hepatotoxicity. Blood was collected for the
      evaluation of liver biochemical markers and livers were removed for
      histopathological evaluation 24 h post-paracetamol treatment. HPLC analysis
      revealed the presence of quercetin, gallic acid, caffeic acid and chlorogenic
      acid in both plant extracts. The extracts of both plants decreased the level of
      alanine aminotransaminase and total bilirubin significantly (p < 0.05), dose
      dependently and protected hepatocytes from paracetamol-induced hepatotoxicity. It
      can be concluded that both plants may possess hepatoprotective activity possibly
      due to the presence of quercetin and phenolic compounds.

PMID- 29224375
TI  - Autoimmune rheumatic diseases and the risk of Parkinson disease: a nationwide
      population-based cohort study in Taiwan.
AB  - BACKGROUNDS: In autoimmune rheumatic diseases (ARDs), the levels of inflammatory
      mediators are increased and microglia may be activated, resulting in an
      inflammatory state and the degeneration of dopaminergic neurons. We investigated
      the association between ARDs and Parkinson disease (PD). METHODS: We identified
      ARD patients through the Taiwan National Health Insurance Research Database from
      2001 to 2012. From the general population, we randomly selected a comparison
      cohort that was frequency-matched by age (in 5-year increments), sex and index
      year. We analysed the risk of PD, stratified by sex, age and comorbidities, by
      using a Cox regression model. RESULTS: The risk of PD was 1.37 times greater in
      ARD patients than in controls after adjustment for age, sex, and comorbidities.
      ARD subgroups, such as the rheumatoid arthritis and Sjogren syndrome (SS)
      cohorts, were associated with a significantly higher risk of PD (adjusted hazard
      ratio [HR], 1.14; 95% confidence interval [CI], 1.03-1.2 and adjusted HR, 1.56;
      95% CI, 1.35-1.79, respectively). Furthermore, primary and secondary SS patients
      had significantly higher risks of PD (adjusted HR, 1.58; 95% CI, 1.32-1.88 and
      adjusted HR, 1.53, 95% CI, 1.23-1.90, respectively). CONCLUSIONS: The risk of PD
      was significantly higher in the ARD patients. Prospective studies are needed to
      confirm whether ARDs indeed increase the risk of PD.

PMID- 29224376
TI  - Regulation of follicle growth through hormonal factors and mechanical cues
      mediated by Hippo signaling pathway.
AB  - The ovary is an interesting organ that shows major structural changes within a
      short period of time during each reproductive cycle. Follicle development is
      controlled by local paracrine and systemic endocrine factors. Many hormonal and
      molecular analyses have been conducted to find the mechanisms underlying
      structural changes in ovaries, However, exact mechanisms still remain to be
      determined. Recent development of mechanobiology facilitates the understanding on
      the contribution of physical forces and changes in the mechanical properties of
      cells and tissues to physiology and pathophysiology. The Hippo signaling pathway
      is one of the key players in mechanotransduction, providing an understanding of
      the molecular mechanisms by which cells sense and respond to mechanical signals
      to regulate cell proliferation and apoptosis for maintaining optimal organ sizes.
      Our group recently demonstrated the involvement of the Hippo signaling pathway in
      the regulation of ovarian follicle development. Fragmentation of ovarian cortex
      into small cubes changed cytoskeletal actin dynamics and induced disruption of
      the Hippo signaling pathway, leading to the production of CCN growth factors and
      anti-apoptotic BIRC. These factors, in turn, stimulated secondary follicle growth
      in vitro and in vivo. In this review, we summarized hormonal regulation of
      follicular structural changes and further focused on the role of Hippo signaling
      in the regulation of follicle development. We also suggest a new strategy of
      infertility treatments in patients with polycystic ovary syndrome and primary
      ovarian insufficiency based on mechanobiology.

PMID- 29224377
TI  - Two new secolignans from the roots of Urtica fissa.
AB  - Two new secolignans, 3,4-trans-3-hydroxymethyl-4-[bis(4-hydroxy-3-
      methoxyphenyl)methyl]butyrolactone (1) and 3,4-trans-3-hydroxymethyl-4- [bis(3,4
      dimethoxyphenyl)methyl]butyrolactone (2) have been isolated from the roots of
      Urtica fissa E.Pritz. Their structures were determined on the basis of
      spectroscopic methods, especially 1H NMR, 13C NMR, 2D NMR, and HR-ESI-MS. The
      inhibitory effects on N1 and N2, two subtypes of neuraminidases (NAs), of these
      two compounds were assayed.

PMID- 29224378
TI  - Carotane-type sesquiterpenes from cultures of the insect pathogenic fungus Isaria
      fumosorosea.
AB  - Two new carotane-type sesquiterpenes named trichocaranes E (1) and F (2), along
      with two known ones CAF-603 (3) and trichocarane C (4), were isolated from
      cultures of the insect pathogenic fungus Isaria fumosorosea. Their structures and
      relative configurations were elucidated by extensive spectroscopic analysis and X
      ray crystallography. Compounds 1-3 showed potent cytotoxic activities against six
      tumor cell lines MDA, MCF-7, SKOV-3, Hela, A549, HepG2 with IC50 values in a
      concentration range of 0.1-6.0 MUg/ml.

PMID- 29224379
TI  - Just-in-time consent: The ethical case for an alternative to traditional informed
      consent in randomized trials comparing an experimental intervention with usual
      care.
AB  - Informed consent for randomized trials often causes significant and persistent
      anxiety, distress and confusion to patients. Where an experimental treatment is
      compared to a standard care control, much of this burden is potentially avoidable
      in the control group. We propose a "just-in-time" consent in which consent
      discussions take place in two stages: an initial consent to research from all
      participants and a later specific consent to randomized treatment only from those
      assigned to the experimental intervention. All patients are first approached and
      informed about research procedures, such as questionnaires or tests. They are
      also informed that they might be randomly selected to receive an experimental
      treatment and that, if selected, they can learn more about the treatment and
      decide whether or not to accept it at that time. After randomization, control
      patients undergo standard clinical consent whereas patients randomized to the
      experimental procedure undergo a second consent discussion. Analysis would be by
      intent-to-treat, which protects the trial from selection bias, although not from
      poor acceptance of experimental treatment. The advantages of just-in-time consent
      stem from the fact that only patients randomized to the experimental treatment
      are subject to a discussion of that intervention. We hypothesize that this will
      reduce much of the patient's burden associated with the consent process, such as
      decisional anxiety, confusion and information overload. We recommend well
      controlled studies to compare just-in-time and traditional consent, with
      endpoints to include characteristics of participants, distress and anxiety and
      participants' understanding of research procedures.

PMID- 29224380
TI  - Ethics and practice of Trials within Cohorts: An emerging pragmatic trial design.
AB  - BACKGROUND: With increasing emphasis on pragmatic trials, new randomized clinical
      trial designs are being proposed to enhance the "real world" nature of the data
      generated. We describe one such design, appropriate for unmasked pragmatic
      clinical trials in which the control arm receives usual care, called "Trials
      within Cohorts" that is increasingly used in various countries because of its
      efficiency in recruitment, advantages in reducing subject burden, and ability to
      better mimic real-world consent processes. METHODS: Descriptive, ethical, and US
      regulatory analysis of the Trials within Cohorts design. RESULTS: Trials within
      Cohorts design involves, after recruitment into a cohort, randomization of
      eligible subjects, followed by an asymmetric treatment of the two arms: those
      selected for the experimental arm provide informed consent for the intervention
      trial, while the data from the control arm are used based on prior broad
      permission. Thus, unlike the traditional Zelen post-randomization consent design,
      the cohort participants are informed about future research within the cohort;
      however, the extent of this disclosure currently varies among studies. Thus,
      ethical analysis is provided for two types of situations: when the pre
      randomization disclosure and consent regarding the embedded trials are fairly
      explicit and detailed versus when they consist of only general statements about
      future data use. These differing ethical situations could have implications for
      how ethics review committees apply US research rules regarding waivers and
      alterations of informed consent. CONCLUSION: Trials within Cohorts is a promising
      new pragmatic randomized controlled trial design that is being increasingly used
      in various countries. Although the asymmetric consent procedures for the
      experimental versus control arm subjects can initially raise ethical concerns, it
      is ethically superior to previous post-randomization consent designs and can have
      important advantages over traditional trial designs.

PMID- 29224381
TI  - Natural aldehyde extraction and direct preparation of new blue light-emitting
      imidazo[1,5-a]pyridine fluorophores.
AB  - This work describes the extraction of natural aldehydes and the use of extracts
      to synthesise new fluorescent imidazo[1,5-a]pyridine derivatives. The
      characterisation of the extracted aldehydes by different techniques and the
      optical study of the fluorescent products allow the design of new compounds
      suitable for pharmaceutical, down-shifting, microscopy and electronic
      applications. The fluorophores are generated by an easy one-pot cyclisation
      reaction in mild conditions without catalyst and with only water as by-product.

PMID- 29224382
TI  - Chemical and pharmacological comparison of modern and traditional dosage forms of
      Joshanda.
AB  - Recently, a traditional remedy (Joshanda) has been replaced largely by modern
      ready-to-use dosage forms, which have not been compared to the original remedy.
      Therefore, the present study aimed to compare a number of modern dosage forms
      with traditional remedy. Seven brands, 3 batches each, were compared with a Lab
      made formulation with reference to analytical (proximate analyses, spectroscopic
      and chromatographic metabolomes) and pharmacological profiles (anti-inflammatory
      and antibacterial activities). Chemical and pharmacological differences were
      found between Lab-made Joshanda and modern dosage forms. Such variations were
      also found within the brands and batches of modern formulations (p < 0.05). The
      Lab-made Joshanda showed significantly higher pharmacological activities as
      compared to modern brands (p ). The results of the present study indicate that
      modern dosage forms are unstandardised and less effective than the traditional
      remedy. Characteristic profiles obtained from Lab-made Joshanda may be used as
      reference to produce comparable dosage forms.

PMID- 29224383
TI  - ABCB1: is there a role in the drug treatment of Parkinson's disease?

PMID- 29224386
TI  - Sexual Homicides in China: Exploring the Offender, Victim, and Offense
      Characteristics.
AB  - Nearly all information available on sexual homicides are limited to studies
      conducted in the West. Little is known about sexual homicides that occurred in
      China. The current study is arguably the first to explore the offender, victim,
      and offense characteristics of Chinese sexual homicides. Over a period of 23
      years (1994 to 2016), the data of 59 cases collected from two data sources (i.e.,
      published Chinese case reports and police data) are examined. Findings indicate
      that heterosexual assaults are far more prevalent in Chinese sexual homicides.
      Sexual murderers who averagely aged 32.44 years are mostly males (97%), single
      (67%), secondary school educated (68%), and with no prior overall (80%) and
      sexual (88%) convictions. The victims are mostly females (83%) with mean age of
      35.35 years. The frequently observed offending patterns include strangers as
      victim choice (63%), con tactics as victim approach method (57%), sexual pleasure
      as primary motivation (49%), and personal weapons as murder weapon of choice
      (41%). Vaginal penetration is a commonly observed sexual assault (88%) and victim
      body mutilation is also not uncommon (47%). Three case examples are also
      presented to illustrate the diverse nature and offending patterns of Chinese
      sexual homicide offenders.

PMID- 29224384
TI  - New coumarin from the roots of Prangos pabularia.
AB  - The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3
      methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O
      beta-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-beta-D-glucopyranoside
      (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7),
      heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose
      (11), have been isolated from the roots of Prangos pabularia, and the structures
      of these isolated compounds were elucidated by spectroscopic means, especially,
      UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic
      effect of yuganin A and its inhibitory effect on B16 cells were evaluated.
      Yuganin A may be useful in the treatment of hyperpigmentation and as a skin
      whitening agent in the cosmetics industry.

PMID- 29224387
TI  - It is Written in Your Eyes: Hostile Attributions and Self-Directed Gaze
      Perception in Incarcerated Violent Adolescent Male Offenders.
AB  - To date, we have frugal knowledge about the hostile attribution bias (HAB) and
      the biased gaze perception in violent adolescent offenders. This however is a
      major contributing factor in understanding delinquent behavior. Using a computer
      based approach, presenting faces modulated in gaze direction (0 degrees , 2
      degrees , 4 degrees , 6 degrees , 8 degrees ) and valence (angry, fearful, happy,
      neutral), the present study examined the impact of HAB of the feeling of being
      stared at in a sample of 27 adolescent offenders (aged 17-24 years). The study
      was conducted institution-intern in the Department for Social Therapy of a German
      correctional facility. Results showed that in comparison with faces with negative
      expressions, happy faces were more likely to be perceived as self-directed.
      Interestingly, emotion showed significant influence of the gaze perception in
      only two viewing angles (2 degrees  and 6 degrees ), revealing the role of the
      facial expression in highly ambiguous conditions. Furthermore, hostility did not
      modulate the relationship between the self-referential gaze perception and
      (negative) facial expression. Possible frameworks and limitations of the study
      are discussed.

PMID- 29224388
TI  - Toughing out the business climate.

PMID- 29224385
TI  - Serum glycosylation characterization of osteonecrosis of the femoral head by mass
      spectrometry.
AB  - Osteonecrosis of the femoral head is a recalcitrant and paralyzing disease often
      discovered in the end stage at the time of diagnosis, which is often performed by
      physical examination and diagnostic imaging. Osteonecrosis of the femoral head is
      typically caused by trauma or long-term steroid use. There are over 30 million
      patients in the US taking steroids, and roughly 40% will develop osteonecrosis of
      the femoral head. However, the exact pathophysiological process is not well
      understood. This study aims to examine the alteration in serum glycosylation of
      osteonecrosis of the femoral head using the state-of-the-art analytical tools to
      provide more chemical data for pathophysiology research and possibly biomarker
      discovery. A training set containing 27 serum samples from steroid-induced
      osteonecrosis of the femoral head patients and 25 from gender- and age-matched
      controls was collected and analyzed. Glycosylation of whole serum and site
      specific glycosylation of immunoglobulins are characterized using electrospray
      ionization-Q-time of flight and electrospray ionization-Triple-Quadruple via
      multiple reaction monitoring, respectively. The whole serum glycosylation
      analysis yielded 14 N-glycan compositions and multiple reaction monitoring
      yielded eight glycopeptides that were altered between cases and controls with
      statistical significance. The increase of nonsialylated, nonfucosylated N-glycans
      and decrease of fucosylated N-glycans are associated with the development of
      osteonecrosis of the femoral head. Glycosylation is a posttranslational protein
      modification and is apparently affected by osteonecrosis of the femoral head.
      Future studies with a larger cohort and patients from earlier stage will be
      performed to assess these potential markers' value in disease onset.

PMID- 29224389
TI  - Is a single-payer system the answer for the uninsured?

PMID- 29224390
TI  - Hope in the face of reform.

PMID- 29224391
TI  - Does a medical degree matter anymore?

PMID- 29224392
TI  - The $16 office visit: a preview of change?

PMID- 29224393
TI  - Satisfaction after reform? No guarantees.

PMID- 29224394
TI  - Physician Satisfaction Index.

PMID- 29224395
TI  - A fighting chance for solo practice.

PMID- 29224396
TI  - 'Post office' medicine: the end of first-class service?

PMID- 29224397
TI  - Flexibility: ticket to survival.

PMID- 29224398
TI  - Ready and set for change.

PMID- 29224399
TI  - Your hotline to the players in Washington.

PMID- 29224401
TI  - To keep quality care, keep the profit motive.

PMID- 29224400
TI  - Managed care: hassle-free medical practice?

PMID- 29224402
TI  - Decoding health policy jargon.
AB  - Along with policy, healthcare analysts are inventing a vocabulary that is as
      cryptic as it is paradoxical. In an effort to keep readers informed about the
      fast-paced evolution of healthcare reform, the editors of POSTGRADUATE MEDICINE
      have compiled this summary of some of the key concepts that are currently under
      discussion.

PMID- 29224403
TI  - 'Unnatural' selection: prodding doctors into primary care.

PMID- 29224404
TI  - EDiP: the Epitope Dilution Phenomenon. Lessons learnt from a malaria vaccine
      antigen and its applicability to polymorphic antigens.
AB  - INTRODUCTION: Polymorphism in vaccine antigens poses major challenges to
      vaccinologists. The Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) poses
      such a challenge. We found that immunization with a mixture of three variants
      yielded functional antibody levels to all variants comparable to levels induced
      by monovalent immunization. The mechanism behind the observed broadening was
      shown to be an increase in the fraction of cross-reactive antibodies, most likely
      because strain-specific epitopes are present at lower frequency relative to
      conserved epitopes. Areas covered: We hereby introduce the Epitope Dilution
      Phenomenon (EDiP) as a practical strategy for the induction of broad, cross
      variant antibody responses against polymorphic antigens and discuss the utility
      and applicability of this phenomenon for the development of vaccines against
      polymorphic antigens of pathogens like Influenza, HIV, Dengue and Plasmodium.
      Expert commentary: EDiP can be used to broaden antibody responses by immunizing
      with a mixture of at least 3 antigenic variants, where the variants included can
      differ, yet yield broadened responses.

PMID- 29224405
TI  - Phylogeography and genetic population structure of the spadenose shark (Scoliodon
      macrorhynchos) from the Chinese coast.
AB  - The population structure of Scoliodon macrorhynchos from the Chinese coast was
      investigated using the mitochondrial control region. All 19 mtDNA haplotypes from
      219 sequences were identified. Relatively high average haplotype diversity
      (0.797) and relatively low average nucleotide diversity (0.0013) were found
      together with a recent and sudden population expansion. Analysis of the mismatch
      distributions, neutrality tests and Bayesian skyline plot showed a pattern
      consistent with a recent population expansion event that may have taken place
      during the last glacial maximum (LGM). The analysis of molecular variance (AMOVA)
      showed the low genetic differentiation between the populations, which may be a
      general feature of sharks living in coastal areas. The phylogenetic and cluster
      analysis of the mtDNA indicates that two putative groups (K = 2) existed in S.
      macrorhynchos, showing that the Taiwan Strait acted as a biogeographic barrier
      during major drops in the sea level in the late Pliocene epoch.

PMID- 29224406
TI  - Novel psychotherapeutics - a cautiously optimistic focus on Hallucinogens.

PMID- 29224407
TI  - Quantification of regional aerosol deposition patterns as a function of
      aerodynamic particle size in rhesus macaques using PET/CT imaging.
AB  - Aerosol aerodynamic particle size is known to affect deposition patterns of
      inhaled aerosol particles, as well as the virulence of inhaled bioaerosol
      particles. While a significant amount of work has been performed to describe the
      deposition of aerosol particles in the human respiratory tract, only a limited
      amount of work has been performed to describe the deposition of aerosol particles
      in the respiratory tract of nonhuman primates, an animal model commonly utilized
      in pharmacological and toxicological studies, especially in the biodefense field.
      In this study, anesthetized rhesus macaques inhaled radiolabeled aerosols with
      MMADs of 1.7, 3.6, 7.4 and 11.8 um to characterize regional deposition patterns.
      The results demonstrate that the regional deposition pattern shifts as particle
      size increases, with greater deposition in more proximal regions of the
      respiratory tract and decreased deposition in the pulmonary region. The results
      of this study extend the findings of previous studies which demonstrated a
      similar shift in the deposition pattern as a function of particle size by
      providing greater resolution of deposition patterns. These data on regional
      deposition patterns provide a starting point to begin to explore potential
      mechanisms responsible for the differences in virulence of infectious bioaerosols
      as a function of particle size and deposition pattern reported in previous
      studies. Additionally, the data are useful to assess the performance of various
      deposition models that have been published in the literature.

PMID- 29224408
TI  - Oral anticoagulation therapy upon discharge in hospitalized patients with
      nonvalvular atrial fibrillation: a retrospective cohort study.
AB  - OBJECTIVES: Availability of direct oral anticoagulants and CHA2DS2VASc/HAS-BLED
      scoring tools underscore the importance of appropriate and safe use of oral
      anticoagulation therapy (OACT). The purpose of this study was to evaluate stroke
      prevention pharmacotherapy in adult patients with nonvalvular atrial fibrillation
      (NVAF) discharged from a large, community-based hospital. METHODS: A
      retrospective cohort study was conducted using a de-identified data collection
      sheet for data extraction (demographics, admitting diagnosis, OACT prior to
      admission and at discharge, concomitant medications that could increase bleed
      risk and/or acid-suppressive therapies). CHA2DS2VASc and HAS-BLED scores were
      calculated. Descriptive statistics were generated to describe all parameters.
      Frequency counts and percentages summarized categorical variables while mean +/-
      standard deviation were determined for continuous variables. RESULTS: Data from
      180 patients were evaluated and of these 177 (98.3%) received OACT regardless of
      stroke risk upon discharge, as determined by CHA2DS2VASc scoring tool. The mean
      CHA2DS2VASc and HAS-BLED scores were 3.61 +/- 1.7 and 2.13 +/- 1.26,
      respectively. At discharge, eight patients at low-stroke risk received OACT for
      unclear reasons, one intermediate-stroke risk patient received aspirin only, and
      two patients at high-stroke risk did not receive OACT due to concerns about
      bleeds. In 66 patients at high-bleed risk, only half received concomitant acid
      suppressive therapy. CONCLUSIONS: Decision to add OACT is often guideline-driven,
      however, individualized circumstances in which clinicians and patients find
      themselves are also important considerations. Determination of ischemic stroke
      risk should be performed with CHA2DS2VASc scoring tool to exclude patients who
      may not benefit from OACT. HAS-BLED scoring tool should be used to identify any
      modifiable bleeding risk factors present with subsequent initiation of management
      strategies. Availability of complete medical histories and meticulous
      documentation are necessary for multiple clinicians to continuously determine
      optimal pharmacotherapy during follow-up visits.

PMID- 29224409
TI  - Intellectual property considerations for molecular diagnostic development with
      emphasis on companion diagnostics.
AB  - INTRODUCTION: The development of molecular diagnostics is a complex endeavor,
      with multiple regulatory pathways to consider and numerous approaches to
      development and commercialization. Companion diagnostics, devices which are
      "essential for the safe and effective use of a corresponding drug or diagnostic
      product" (see U.S. Food & Drug Administration, In Vitro Diagnostics - Companion
      Diagnostics, U.S. Dept. of Health & Human Services(2016), available at
      https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostic
      /ucm407297.htm ) and complementary diagnostics, which are more broadly associated
      with a class of drug, are becoming increasingly important as integral components
      of the implementation of precision medicine. Areas covered: The following article
      will highlight the intellectual property ('IP') considerations pertinent to
      molecular diagnostics development with special emphasis on companion diagnostics.
      Expert opinion/commentary Summary: For all molecular diagnostics, intellectual
      property (IP) concerns are of paramount concern, whether the device will be
      marketed only in the United States or abroad. Taking steps to protect IP at each
      stage of product development is critical to optimize profitability of a
      diagnostic product. Also the legal framework around IP protection of diagnostic
      technologies has been changing over the previous few years and can be expected to
      continue to change in the foreseeable near future, thus, a comprehensive IP
      strategy should take into account the fact that changes in the law can be
      expected.

PMID- 29224410
TI  - Reduction of opioid use and improvement in chronic pain in opioid-experienced
      patients after topical analgesic treatment: an exploratory analysis.
AB  - OBJECTIVE: There is a need to identify safe and effective opioid-sparing
      multimodal alternative treatment strategies and approaches, including topical
      analgesics, for opioid-experienced chronic pain patients to mitigate the risk of
      addiction, misuse, and abuse of opioids. METHODS: This subset analysis from a
      prospective, observational study evaluated changes in opioid use, other
      concurrent medication use, and pain severity and interference in opioid
      experienced patients (OEP) treated with topical analgesics for chronic pain with
      measures obtained at baseline and 3- and 6- month follow-up. RESULTS: The 3-month
      opioid-experienced patient (3-month OEP) group included 121 patients who
      completed baseline and 3-month follow-up assessments; 27 opioid-experienced
      patients completed baseline and 6-month follow-up assessments (6-month OEP).
      Demographic characteristics, and mean pain severity and interference scores were
      similar between groups at baseline. After treatment with topical analgesics, 49%
      of patients in the 3-month and 56% of patients in the 6-month group reported they
      had completely discontinued use of opioids. In addition, 31% of patients at the 3
      month assessment and 30% at the 6-month assessment reported that they were no
      longer taking any pain medication. Other concurrent medications decreased by 65%
      after 3 months, and 74% after 6 months. There were statistically significant
      decreases from baseline in pain severity and interference scores within the 3-
      (CI:0.7-1.4, 1.4-2.2) and 6-month (CI:0.7-2.4 (severity); CI:1.2-3.5
      (interference)) OEP groups. CONCLUSIONS: Opioid use and other concurrent
      medications decreased among opioid-experienced chronic pain patients after 3- and
      6- months of treatment with topical analgesics. Pain severity and interference
      scores also decreased. The topical analgesics were reported to be effective and
      safe for the treatment of chronic pain, with randomized controlled trials needed
      to confirm these findings.

PMID- 29224411
TI  - Change in Quantitative EEG Theta Cordance as a Potential Predictor of Repetitive
      Transcranial Magnetic Stimulation Clinical Outcome in Major Depressive Disorder.
AB  - Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in
      major depressive disorder (MDD), although clinical outcome is variable. Change in
      the resting-state quantitative electroencephalogram (qEEG), particularly in theta
      cordance early in the course of treatment, has been linked to antidepressant
      medication outcomes but has not been examined extensively in clinical rTMS. This
      study examined change in theta cordance over the first week of clinical rTMS and
      sought to identify a biomarker that would predict outcome at the end of 6 weeks
      of treatment. Clinically stable outpatients (n = 18) received nonblinded rTMS
      treatment administered to the dorsolateral prefrontal cortex (DLPFC). Treatment
      parameters (site, intensity, number of pulses) were adjusted on an ongoing basis
      guided by changes in symptom severity rating scale scores. qEEGs were recorded at
      pretreatment baseline and after 1 week of left DLPFC (L-DLPFC) rTMS using a 21
      channel dry-electrode headset. Analyses examined the association between week 1
      regional changes in theta band (4-8 Hz) cordance, and week 6 patient- and
      physician-rated outcomes. Theta cordance change in the central brain region
      predicted percent change in Inventory of Depressive Symptomology-Self-Report (IDS
      SR) score, and improvement versus nonimprovement on the Clinical Global
      Impression-Improvement Inventory (CGI-I) ( R2 = .38, P = .007; and Nagelkerke R2
      = .78, P = .0001, respectively). The cordance biomarker remained significant when
      controlling for age, gender, and baseline severity. Treatment-emergent change in
      EEG theta cordance in the first week of rTMS may predict acute (6-week) treatment
      outcome in MDD. This oscillatory synchrony biomarker merits further study in
      independent samples.

PMID- 29224412
TI  - A Cure for Hemophilia within Reach.

PMID- 29224414
TI  - Using Photovoice to Explore Quality of Life Factors of Adults With Crouzon
      Syndrome.
AB  - In the United States, one in 60,000 adults live with Crouzon Syndrome (CS) and
      facial malformations. Phenomenological studies about their lived experiences and
      quality of life are lacking. The purpose of this participatory action research
      study was to gain a richer understanding of the perceived biopsychosocial and
      socioecological factors that impact quality of life for adults living with CS
      using Photovoice. Another aim was to develop a conceptual framework of quality of
      life for those experiencing CS to enhance tailored health education and services.
      A purposeful sample of nine adults with CS were recruited from U.S. national
      surgery centers and support groups. Participants used photography to represent
      their experiences and participated in individual interviews and focus groups.
      Data were analyzed with the participants using thematic analysis, and 44 themes
      emerged which informed the development of a quality of life conceptual framework
      and action plan described in this article.

PMID- 29224413
TI  - Low HOX gene expression in PML-RARalpha-positive leukemia results from suppressed
      histone demethylation.
AB  - Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies
      have shown that aberrant HOX gene expression accompanies leukemogenesis and
      affects disease progression and leukemia patient survival. Patients with acute
      myeloid leukemia (AML) bearing PML-RARalpha fusion gene have distinct HOX gene
      signature in comparison to other subtypes of AML patients, although the mechanism
      of transcription regulation is not completely understood. We previously found an
      association between the mRNA levels of HOX genes and those of the histone
      demethylases JMJD3 and UTX in PML-RARalpha- positive leukemia patients. Here, we
      demonstrate that the release of the PML-RARalpha-mediated block in PML-RARalpha
      positive myeloid leukemia cells increased both JMJD3 and HOX gene expression,
      while inhibition of JMJD3 using the specific inhibitor GSK-J4 reversed the
      effect. This effect was driven specifically through PML-RARalpha fusion protein
      since expression changes did not occur in cells with mutated RARalpha and was
      independent of differentiation. We confirmed that gene expression levels were
      inversely correlated with alterations in H3K27me3 histone marks localized at HOX
      gene promoters. Furthermore, data from chromatin immunoprecipitation followed by
      sequencing broaden a list of clustered HOX genes regulated by JMJD3 in PML
      RARalpha-positive leukemic cells. Interestingly, the combination of GSK-J4 and
      all-trans retinoic acid (ATRA) significantly increased PML-RARalpha-positive cell
      apoptosis compared with ATRA treatment alone. This effect was also observed in
      ATRA-resistant NB4 clones, which may provide a new therapeutic opportunity for
      patients with acute promyelocytic leukemia (APL) resistant to current treatment.
      The results of our study reveal the mechanism of HOX gene expression regulation
      and contribute to our understanding of APL pathogenesis.

PMID- 29224415
TI  - Preclinical evaluation of saroglitazar magnesium, a dual PPAR-alpha/gamma agonist
      for treatment of dyslipidemia and metabolic disorders.
AB  - 1. Saroglitazar, a novel peroxisome proliferator-activated receptor (PPAR)
      agonist, regulates lipid and glucose metabolism. The objective of this report is
      to provide a preclinical evaluation (in vitro/in vivo) of ADME properties of
      saroglitazar. In vitro studies included determination of permeability, metabolic
      stability, plasma protein binding, CYP reaction phenotyping and CYP inhibitory
      liability. In vivo studies included oral bioavailability and pharmacokinetic
      assessment in mouse, rat and dog. The excretion of saroglitazar was determined in
      rats. Exploratory metabolism of saroglitazar was evaluated using in vitro and in
      vivo samples. 2. Saroglitazar was metabolically more stable in human liver
      microsomes as compared to rat and dog liver microsomes, highly protein bound (98
      99.6%) with high Caco2 permeability (104 nm/s) with <2 efflux ratio. In vitro
      metabolism in rat, dog and human liver microsomes revealed three putative
      metabolites corresponding to di-hydroxylation, mono-oxygenation and
      dehydrogenation moieties. 3. Oral bioavailability was 100%, 72% and 47% in mouse,
      rat and dog, respectively. The intravenous clearance and volume of distribution
      of saroglitazar were 3.6, 8.5 and 6.9 mL/min/kg and 1.3, 4.8 and 1.8 L/kg for
      mouse, rat and dog, respectively. The elimination half-life of saroglitazar
      ranged between 6 and 15 h. Saroglitazar appeared to be eliminated via
      hepatobiliary route with negligible renal excretion.

PMID- 29224416
TI  - Utilising three-dimensional printing techniques when providing unique assistive
      devices: A case report.
AB  - BACKGROUND: The evolution of three-dimensional printing into prosthetics has
      opened conversations about the availability and cost of prostheses. This report
      will discuss how a prosthetic team incorporated additive manufacture techniques
      into the treatment of a patient with a partial hand amputation to create and test
      a unique assistive device which he could use to hold his French horn. Case
      description and methods: Using a process of shape capture, photogrammetry,
      computer-aided design and finite element analysis, a suitable assistive device
      was designed and tested. The design was fabricated using three-dimensional
      printing. Patient satisfaction was measured using a Pugh's MatrixTM, and a cost
      comparison was made between the process used and traditional manufacturing.
      Findings and outcomes: Patient satisfaction was high. The three-dimensional
      printed devices were 56% cheaper to fabricate than a similar laminated device.
      CONCLUSION: Computer-aided design and three-dimensional printing proved to be an
      effective method for designing, testing and fabricating a unique assistive
      device. Clinical relevance CAD and 3D printing techniques can enable devices to
      be designed, tested and fabricated cheaper than when using traditional
      techniques. This may lead to improvements in quality and accessibility.

PMID- 29224417
TI  - Parental Responses to Temper Outbursts in Children With ADHD: The Role of
      Psychological Factors.
AB  - OBJECTIVE: Children with ADHD frequently exhibit temper outbursts (TO). One
      related factor may be parental responses, such as harsh discipline and
      accommodation. This study tests the hypotheses that these responses will be
      associated with greater TO, and parental characteristics of higher anger and
      lower sense of competence, in children with ADHD. METHOD: Participants included
      79 5- to 9-year-old children with ADHD (77.22% boys). Regressions were used to
      determine the association between parental psychological factors and responses to
      TO while covarying for TO frequency, severity, and duration. RESULTS: Parental
      anger and sense of competence were not significantly related to any discipline
      responses after covarying for TO characteristics, although sense of competence
      predicted spanking at trend-level significance. Both parental anger and sense of
      competence significantly predicted accommodation over and above TO
      characteristics. CONCLUSION: Results underscore the importance of parental anger
      and sense of competency in predicting parental behavior, specifically parental
      accommodation.

PMID- 29224418
TI  - The Characteristics and Age Effects of Emotional Lability in ADHD Children With
      and Without Oppositional Defiant Disorder.
AB  - OBJECTIVE: This study evaluated the concurrent validity of emotional lability
      (EL) in children with ADHD. METHOD: A total of 2,015 children with ADHD and 745
      typically developed controls (TDCs) were assessed and compared on EL. RESULTS:
      ADHD participants expressed higher EL scores than TDCs, not influenced by gender
      or IQ. Higher levels of EL symptoms were found in children with comorbid
      oppositional defiant disorder (ODD) and with ADHD-combined subtype. Receiver
      operating characteristic (ROC) analyses showed a strong screening efficacy of EL
      symptoms on ADHD. The effect of developmental age on EL showed a desisting
      pattern in TDCs, as opposed to a persisting pattern in ADHD (not influenced by
      ODD comorbid status). ODD symptoms in ADHD showed an ascending pattern.
      CONCLUSION: EL can potentially serve as a sentinel index for the presence of
      ADHD, especially when the ADHD presentation is atypical. ODD may embody a
      developmental entity distinct from EL.

PMID- 29224419
TI  - Expanding the Phenotype of ALK-positive Histiocytosis: A Report of 2 Cases.
AB  - ALK-positive histiocytosis is a recently described rare histiocytic proliferative
      disorder of early infancy. When infants present with anemia, thrombocytopenia,
      and hepatosplenomegaly, this entity should be included in the differential
      diagnosis along with hemophagocytic lymphohistiocytosis, metabolic/storage
      diseases, hematopoietic malignancies, and autoimmune thrombocytopenia. We report
      2 new cases of ALK-positive histiocytosis, one with kidney involvement and the
      other with extensive bone marrow involvement in addition to an overt liver
      disease. Renal involvement by ALK-positive histiocytosis has not been reported.
      The infiltrating histiocytes in this case showed Rosai-Dorfman disease-like
      morphology including emperipolesis. The histiocytes in the second case with
      extensive bone marrow involvement had foamy cytoplasm initially suggesting
      storage disease. Our 2 cases highlight previously unrecognized diversity of ALK
      positive histiocytosis in clinical manifestation, organ involvement, and
      cytomorphologic features and further elucidate the diagnostic challenges of this
      rare entity.

PMID- 29224420
TI  - Plaque-like Myofibroblastic Tumor: 2 Cases of This Unusual Dermal Tumor Which
      Occurs in Infancy and Early Childhood.
AB  - Plaque-like myofibroblastic tumor (PLMT) is a rare dermal spindle cell tumor
      which occurs in infancy or childhood within the first 4 years of life. The tumor
      is often pruritic and mostly presents on the lower back. We describe 2 cases with
      characteristic clinical and histological features of this entity, thus adding to
      the 10 cases which have so far been reported. Histologically, the lesion
      resembles a dermatofibroma. However, diffuse and uniform immunohistochemical
      staining with smooth muscle actin favors a myofibroblastic lineage. PLMT should
      be considered in the differential diagnosis of a dermal spindle cell tumor in the
      pediatric age-group.

PMID- 29224421
TI  - Hydrolysis, setting properties and in vitro characterization of
      wollastonite/newberyite bone cement mixtures.
AB  - Bone cements based on magnesium phosphates such as newberyite (N; MgHPO4.3H2O)
      have been shown as potential bone substitutes due to their biocompatibility,
      biodegradability and ability to support osteoblast differentiation and
      proliferation. Newberyite can hydrolyze to hydrated magnesium phosphate compounds
      (e.g. bobierite (Mg3(PO4)2.8H2O)) at alkaline conditions. In this study, 25 and
      50 wt% of crystalline beta -wollastonite (woll; CaSiO3) was admixed to newberyite
      powder in order to both enhance the acid-base hydrolysis of newberyite and to
      produce a functional bone cement. The setting process of wollastonite/newberyite
      cement mixtures started with the hydrolysis of the wollastonite with further
      transformation of newberyite into bobierite and the formation of magnesium
      silicate phase. The results demonstrated that 25 wollastonite/newberyite and 50
      wollastonite/newberyite cement pastes at optimal powder/liquid ratios had final
      setting times of ~34 and 25 min and compressive strength values of 18 and 32 MPa
      after seven days setting, respectively. The tests of cytotoxicity of cement
      extracts on osteoblastic cells and contact cytotoxicity of the cement substrates
      showed different results. The osteoblasts cultured in cement extracts readily
      proliferated which confirmed the non-cytotoxic concentration of ions released
      from both cements. On the other hand, a strong cytotoxic character of 25
      wollastonite/newberyite sample surface in contrary to high (~80%) proliferation
      activity of cells on the 50 wollastonite/newberyite cement substrate was
      observed. The differences in cell proliferation activity was attributed to
      different surface topographies of cement substrates, where needle-like
      precipitated microcrystals of magnesium phosphate phase (in 25
      wollastonite/newberyite cement) prevented the adhesion and proliferation of
      osteoblasts contrary to the smoother surface covered by extremely fine
      nanoparticles in the 50 wollastonite/newberyite cement.

PMID- 29224422
TI  - Thyroiditis.
AB  - Preview How does subacute thyroiditis differ from silent thyroiditis? What is an
      important clue in the diagnosis of Hashimoto's thyroiditis? Why is it difficult
      to distinguish the various inflammatory conditions of the thyroid gland? The
      authors of this article offer a useful guide to sorting out the signs and
      symptoms of the five types of thyroiditis.

PMID- 29224423
TI  - Perioperative management of thyroid disease.
AB  - Preview In discussions of the perioperative management of patients with thyroid
      disease, the wise axiom "an ounce of prevention is worth a pound of cure" remains
      especially applicable. Mortality rates with thyroid storm and myxedema coma, the
      most extreme complications, are still exceedingly high. In this article, the
      authors discuss the physiologic effects of thyroid disorders that adversely
      affect surgical risk. They also recommend preventive measures.

PMID- 29224424
TI  - Antibiotic prophylaxis for medical and dental procedures.
AB  - Preview Are prophylactic antibiotics really needed to prevent endocarditis and
      prosthetic joint infection when patients at risk undergo medical and dental
      procedures likely to cause bacteremia? Although animal studies seem to support
      such prophylaxis, clinical trials in humans are lacking, and some authorities
      believe it is unethical to give antibiotics without more evidence of benefit. Dr
      Uyemura examines the problem in this article.

PMID- 29224425
TI  - Preparticipation sports examinations.
AB  - Preview In most states, an examination is required before school-aged youngsters
      are allowed to play recreational and competitive sports. Examining physicians are
      responsible for conducting a thorough yet cost-effective evaluation to detect
      disqualifying or restricting conditions. The authors summarize the aspects to
      consider during history taking and physical examination and provide guidelines
      approved by the American Academy of Pediatrics.

PMID- 29224427
TI  - Giardiasis.
AB  - Preview Although infection with Giardia lamblia is common, identifying it can be
      a challenge. Laboratory testing is not always definitive, even in patients with
      characteristic gastrointestinal symptoms. Fortunately, antiprotozoal therapy is
      effective in most cases. In this article, Dr Babb discusses current diagnostic
      methods and outlines an effective approach to treatment.

PMID- 29224426
TI  - Allergic drug reactions.
AB  - Preview With most drugs, the risk of an allergic reaction is small, but not
      insignificant. What factors increase the risk? Do certain groups of patients have
      inherent risk factors for particular reactions? What should clinicians keep in
      mind about reactions to penicillins? sulfonamides? aspirin and NSAIDs? Dr
      Bernstein answers these and other questions and provides an algorithm for
      managing the care of patients with a history of drug allergy.

PMID- 29224428
TI  - Niacin for lipid disorders.
AB  - Preview Of the lipid-lowering agents, niacin (nicotinic acid) has been available
      the longest. Its efficacy in lowering LDL cholesterol and triglyceride levels and
      in raising HDL cholesterol levels makes it very useful for many patients.
      However, the frequency of adverse reactions in persons taking niacin has
      inhibited physicians from using the agent optimally in practice. In this article,
      Dr Brown examines its current role in the treatment of dyslipidemia.

PMID- 29224429
TI  - Is your patient using cocaine?
AB  - Preview Cocaine may bring a feeling of euphoria, but the short-lived high often
      comes with lasting adverse consequences. Because use of the drug is on the rise,
      primary care physicians should be familiar with its attendant medical
      complications. How does cocaine affect the heart? The lungs? The nervous system?
      Which bodily functions does it inhibit? Or enhance? Dr Warner answers these and
      other questions in this overview of the medical consequences of cocaine use.

PMID- 29224430
TI  - Thyroid screening.
AB  - Preview The ultrasensitive third-generation assay for thyrotropin (TSH) is now
      the "gold standard" for measuring thyroid activity. Who should be screened with
      it, and what further studies should be done if results are abnormal? Which
      patients with subclinical disease should receive treatment? Drs Brody and
      Reichard discuss these and other issues and provide an algorithm for thyroid
      screening.

PMID- 29224431
TI  - Endoscopic evaluation of iron deficiency anemia.
AB  - Preview Iron deficiency occurs in about 2% of US adults over age 50 and is a
      common cause of anemia. Opinions differ on the approach to evaluation of iron
      deficiency anemia in older patients, and studies have yielded conflicting
      results. What is the best diagnostic strategy? The authors review study results
      for the various options and recommend a stepwise, systematic approach to
      evaluation.

PMID- 29224432
TI  - When to worry about headache.
AB  - Preview Nine of 10 patients who seek medical attention for head pain have a
      migraine, tension-type, or cluster headache. Sometimes, however, head pain is a
      symptom of a more serious condition requiring prompt diagnosis and treatment. How
      can you determine if a headache is potentially dangerous? Drs Perkins and Ondo
      tell you how to avoid misdiagnosis with directed history taking and physical
      examination, as well as appropriate neurologic evaluation and diagnostic testing.

PMID- 29224433
TI  - Solitary thyroid nodules.
AB  - Preview Diagnostic evaluation of a thyroid nodule is an important undertaking but
      need not be complex. Often, physicians can rapidly categorize a nodule as benign
      or malignant with reasonable accuracy through history taking, physical
      examination, laboratory studies, and diagnostic imaging. Results of fine-needle
      aspiration biopsy can then guide further steps in diagnosis and treatment. The
      authors describe key elements in the evaluation process.

PMID- 29224434
TI  - Percutaneous intervention to correct central venous port catheter malposition.
AB  - The use of central venous port access is increasing due to the requirements of
      multimodal intravenous therapy.1 However, catheter malposition in smaller veins
      can lead to vein thrombosis, phlebitis and pain. Herein, we report our experience
      with the use of percutaneous interventions to correct migrated port catheter
      malposition. Minimally invasive percutaneous interventional correction of
      malposition could be an alternative to extraction and re-implantation of
      malpositioned port catheters.

PMID- 29224435
TI  - Pediculosis and scabies.
AB  - Preview The thought of parasites usually triggers revulsion and horror, and lice
      infestations have generated many words and phrases with unpleasant connotations
      (eg, feeling lousy, dirty louse, nit-picker). Still, humans too often find
      themselves sharing their bodies and living quarters with lice and mites. Dr
      Foreman describes how to accurately diagnose infestations, what to include in
      patient education to calm fears, and how to ensure successful treatment.

PMID- 29224436
TI  - Diaper dermatitis.
AB  - Preview Skin eruptions in the diaper area in infants bring many new parents to
      the primary care physician's office. Which topical agents and diapering
      strategies work best to clear lesions? And how can recurrence be avoided? The
      authors answer these questions and discuss common skin disorders in the diaper
      region as well as several rare disorders that may require dermatologic
      consultation.

PMID- 29224437
TI  - New oral agents for type II diabetes.
AB  - Preview Status quo obviously is not optimal in the management of patients with
      non-insulin-dependent diabetes, given the fact that the average hemoglobin A1c
      value in this diabetic population is between 9% and 10%. There is an impetus,
      therefore, to move up the treatment ladder more quickly than at present. The
      availability of new oral hypoglycemic agents provides the potential for expanding
      the role of this category of agents and for improving overall glycemic control in
      these patients.

PMID- 29224438
TI  - Variceal bleeding.
AB  - Preview The high mortality rate of variceal hemorrhage poses a management
      challenge. A severe bleeding episode requires emergency repletion of blood
      volume. If pharmacologic therapy fails to control bleeding, various endoscopic
      and surgical procedures must be considered. In this article, Drs Stein and Korula
      explore the various options available for managing this difficult medical
      problem.

PMID- 29224439
TI  - Variceal bleeding.
AB  - Preview Prevention of variceal hemorrhage in patients with chronic liver disease
      has been a primary concern for many researchers and practitioners. Because this
      complication is life-threatening, effective prophylaxis may improve survival
      rates by reducing the risk or delaying the onset of bleeding. In this article, Dr
      Korula discusses the likely causes of hemorrhage and explores current options for
      controlling acute bleeding and preventing rebleeding.

PMID- 29224440
TI  - Chronic stable angina pectoris.
AB  - Preview In most patients with stable angina pectoris, symptoms can be controlled
      successfully with drug therapy. Revascularization procedures should be reserved
      for those at high risk for cardiac events and those who do not respond to optimal
      therapy with any of the three classes of antianginal agents. In this article, the
      authors describe tailoring of medical therapy on the basis of concomitant
      disease, outcome of risk stratification, and response to individual agents.

PMID- 29224442
TI  - Skin disorders and primary care.

PMID- 29224441
TI  - Unstable angina pectoris.
AB  - Preview Patients with angina that occurs increasingly often, for longer periods,
      with less and less exertion, or during periods of rest are of particular concern.
      These traits are all characteristic of unstable angina. Unlike stable angina,
      which has a relatively benign course, unstable angina has the capability of
      progressing to acute myocardial infarction or death. The authors summarize
      patient evaluation, with emphasis on identification of those at risk.

PMID- 29224443
TI  - The Christmas Card.

PMID- 29224444
TI  - Superficial fungal infections.
AB  - Preview Didn't mother always tell you to wear shower shoes in the locker room?
      She was right. Athlete's foot is one of several fungal diseases that thrive in
      hot, humid environments. The human body itself can create warm, damp conditions
      where skin folds or rubs. The authors describe clinical presentations of fungal
      infections commonly seen by primary care physicians, treatment regimens to
      relieve patient discomfort, and tips for daily routine care to prevent
      recurrence.

PMID- 29224445
TI  - Nonmelanoma skin cancer.
AB  - Preview Heightened awareness and early diagnosis of skin cancer are vital for
      timely treatment. Primary care physicians who can recognize malignant and
      premalignant lesions of the skin have an important role in improving cure rates,
      limiting morbidity, and decreasing healthcare costs. The authors discuss
      management of basal cell and squamous cell carcinomas, emphasizing risk factors
      and patient education.

PMID- 29224446
TI  - Audio Facilitates the Perception of Cinematic Continuity by First-Time Viewers.
AB  - Previous studies concluded that first-time film viewers often had difficulty
      integrating shots into a coherent representation of the depicted events in the
      absence of a familiar action through the film cuts or a salient eye-gazing of a
      character in the film. In this study, we investigated whether diegetic sound
      (i.e., sound that seems to originate from the depicted cinematic space) could
      effectively bridge shots for first-time viewers. Across a range of films, both
      dialog, and salient environmental sound (e.g., barking dogs) helped first-time
      viewers connect shots. However, sound was not always successful in supporting
      first-time viewers' interpretations. While experienced viewers were able to
      understand less-familiar linking sounds and environments, first-time viewers
      found this difficult. Overall, a range of diegetic sounds helped first-time
      viewers understand spatiotemporal relations between shots, but these viewers
      still had difficulty integrating views of unfamiliar environments.

PMID- 29224447
TI  - Arthritis of recent onset.
AB  - Preview Physicians as well as patients tend to think of arthritis as a chronic,
      slowly progressive disorder. However, it can also first present as a new, acute
      symptom of infection, crystal disease, trauma, and many other joint and systemic
      diseases. Dr Schumacher summarizes how to narrow the possibilities with careful
      history taking and physical examination and what to do and not do until the
      diagnosis is established.

PMID- 29224448
TI  - Systemic lupus erythematosus.
AB  - Preview Although systemic lupus erythematosus affects primarily young and middle
      aged women, a percentage of cases occur in all age-groups and both sexes. That
      fact, coupled with the diversity of clinical presentations, can make diagnosis a
      challenge. This article discusses epidemiologic and pathogenetic factors and
      describes the many manifestations of the disease. A brief overview of current
      treatment is presented.

PMID- 29224449
TI  - Laboratory tests for rheumatic diseases.
AB  - Preview Laboratory testing to aid the diagnosis of rheumatic disease represents
      an area of considerable controversy in the United States. There is growing
      recognition that "overtesting" contributes to the rising costs of healthcare and
      that strategies need to be developed to optimize use of the increasing number of
      available tests. In this article, the authors discuss some of the commonly
      ordered tests for rheumatic diseases, focusing on their usefulness, sensitivity,
      and specificity.

PMID- 29224450
TI  - Physical examination of substance abusers.
AB  - Preview How can physicians make appropriate treatment decisions in substance
      abusers who have serious medical illness, especially when patients may not offer
      the information needed? Drs Westreich and Rosenthal summarize common physical
      findings that suggest abuse of specific substances. Recognizing these signs
      allows physicians to reliably diagnose chemical use, leads to improved outcomes,
      and lends weight to recommendations for substance-abuse therapy.

PMID- 29224451
TI  - Psoriatic arthritis.
AB  - Preview Psoriatic arthritis can precede the onset of psoriatic skin lesions and
      has myriad presentations. Familiarity with its guises allows early institution of
      therapy to control its destructive potential. The authors describe the clinical
      features of psoriatic arthritis in all their variety, indicate what laboratory
      abnormalities and radiographic findings can be expected, and provide an update on
      agents used in therapy.

PMID- 29224452
TI  - Migraine and women.
AB  - Preview Successful management of migraine in women requires an understanding of
      the effects changing sex hormone levels have on headache patterns. In this
      article, Dr Silberstein explains the modulating and triggering effects of the sex
      hormones during significant hormonal phases of the female life cycle, including
      menarche and menstruation, pregnancy, oral contraceptive use, and menopause.
      Pharmacologic management and prophylaxis of migraine are the focus of his
      discussion.

PMID- 29224453
TI  - Erectile dysfunction.
AB  - Preview More than half of men over 40 may have some form of sexual dysfunction,
      and erectile dysfunction is by far their most common presenting symptom. What are
      the risk factors that suggest an organic cause for erectile dysfunction? Which
      diagnostic tests are appropriate for which patients? Dr Guay answers these and
      other questions, providing a thorough guide to medical evaluation of the problem,
      and discusses specific and nonspecific therapies.

PMID- 29224454
TI  - Acute lower gastrointestinal bleeding.
AB  - Preview Where are bleeding angiodysplastic lesions and diverticula most commonly
      found? What are the uses of radionuclide bleeding scans and selective mesenteric
      angiography? When is surgical intervention warranted for patients with acute
      lower gastrointestinal bleeding? Drs Manten and Green provide practical answers
      to these and other questions in this overview of diagnostic and therapeutic
      options.

PMID- 29224455
TI  - Pulmonary tuberculosis.
AB  - Preview Rather than nearing eradication as health officials hoped, "consumption"
      is a growing concern. It does not merit the adjective "galloping" as in past
      centuries but does deserve the attention of practicing physicians. Dr Colice
      summarizes studies of the current spread of tuberculosis; findings suggest that
      person-to-person transmission is increasing, that resistance is low in native
      born Americans, and that infectivity may be changing because of resistant
      strains.

PMID- 29224456
TI  - How Real is TV's Er?

PMID- 29224457
TI  - Treatment of vincristine-induced ileus with metoclopramide: A case report.
AB  - Introduction Acute lymphoblastic leukemia is an invasive malignancy which ought
      to be treated with several cytotoxic medications. Vincristine-based regimen is
      among the most commonly used regimens for the treatment of adult acute
      lymphoblastic leukemia. Peripheral neuropathy caused by vincristine provides a
      limitation in dose administration and can influence the treatment outcome and
      patient's quality of life. Case presentation Ileus and constipation occurred as a
      result of autonomic neuropathy in a 58-year-old man who underwent vincristine
      based regimen for acute lymphoblastic leukemia treatment. Despite the
      administration of several laxative agents for constipation, the complication did
      not improve. So metoclopramide as a prokinetic agent was administered
      intravenously, and patient bowel movement and defecation started after 24 h.
      Conclusions There is no approved protocol for vincristine-induced autonomic
      neuropathy treatment; thus, prokinetic agents such as metoclopramide can be
      considered as an option for ileus treatment after ruling out the possibility of
      bowel obstruction. Prophylactic stool softeners should be administrated in all
      patients undergoing chemotherapy with vincristine to prevent gastrointestinal
      motility disorders.

PMID- 29224458
TI  - Corticosteroids for the management of immune-related adverse events in patients
      receiving checkpoint inhibitors.
AB  - Introduction Due to enhanced T-cell activity, immune checkpoint inhibitors cause
      immune-related adverse effects. Corticosteroids are the mainstay of immune
      related adverse effect management but the optimal strategy has not been
      determined, putting patients at risk for steroid-related adverse effects and
      potentially decreased efficacy of immunotherapy. This study aims to characterize
      the use of corticosteroids for the management of immune-related adverse effect.
      Methods and materials A retrospective, single-center evaluation of patients
      receiving checkpoint inhibitors was conducted. The primary objective was to
      evaluate corticosteroid use for immune-related adverse effects, including
      starting dose, taper strategy, total duration, and resumption of immunotherapy.
      Secondary objective was to describe the incidence and significance of
      hyperglycemia. Results One hundred and three patients met inclusion criteria and
      experienced 123 immune-related adverse effects. Prednisone was used most commonly
      (67%) at an average starting dose of 0.88 mg/kg (range 0.07-17.0). On average,
      steroid tapers began 9.2 days after initiation (range 0-89) and were continued
      for a total of 84.2 days (range 3-693). In 21.1% of cases, checkpoint inhibitor
      therapy was not delayed and 68.6% resumed checkpoint inhibitors, while the
      patient was taking steroids (30.4 mg prednisone on average, range 5-80). On
      average, checkpoint inhibitor therapy was resumed 18.6 days after detection of
      immune-related adverse effect (range 0-150). Clinically relevant hyperglycemia
      occurred in 8.9%. Conclusion Utilization of steroids for immune-related adverse
      effect at our institution is highly variable. The majority of patients received
      prolonged courses of steroids and resumed checkpoint inhibitor therapy with
      concomitant steroids above recommended doses. Additional monitoring for
      hyperglycemia and other steroid associated adverse effects should be considered.

PMID- 29224459
TI  - Dietary patterns of households in Scotland: Differences by level of deprivation
      and associations with dietary goals.
AB  - BACKGROUND: Foods tend to be consumed in combinations, and dietary pattern
      analysis and diet-quality scores are often more appropriate methods of assessing
      overall diet quality than is intakes of individual foods or nutrients. AIM: The
      aim of this study was to evaluate dietary patterns from the food and drink
      purchases of households in Scotland, and to identify any dietary patterns that
      were associated with closer adherence to the Revised Dietary Goals for Scotland
      (RDGS). METHODS: We carried out a cross-sectional study of estimated food and
      drink intakes using Kantar WorldPanel household purchase data in Scotland
      collected during 2012. The amounts of food and drink purchased were converted to
      estimated amounts available for consumption per person by adjusting for household
      waste, household size and composition ( n = 720). Dietary patterns were
      identified using principal components analysis. A Diet Quality Index (DQI), based
      on the RDGS, was calculated. RESULTS: The mean DQI score was low at 38 out of a
      possible maximum of 100, indicating that, on average, few of the dietary goals
      were being met. Six dietary patterns were identified, which explained 35% of the
      total variance in estimated food and drink intake. Three dietary patterns showed
      statistically significant associations with lower DQI scores (less healthy
      diets), and one with significantly higher DQI scores (healthier diets).
      CONCLUSIONS: Investigating dietary patterns to show which foods tend to be
      purchased together may assist in targeting dietary habits by focussing on key
      food groups, and in gaining the greatest improvement in diet quality from the
      most achievable change in diet.

PMID- 29224460
TI  - Implementation of Rocking Chair Therapy for Veterans in Residential Substance Use
      Disorder Treatment [Formula: see text].
AB  - BACKGROUND: Substance use disorder (SUD) and mental health diagnosis negatively
      affect Veteran homelessness. OBJECTIVE: Assess the acceptance and feasibility of
      rocking chair therapy as a self-implemented intervention for mood and substance
      cravings. PICOT: For homeless Veterans in SUD treatment, how does adding
      vestibular stimulation by use of a rocking chair compared with treatment as usual
      affect levels of anxiety and substance cravings? RESULTS: Two significant
      findings were observed. First, a greater number of minutes spent rocking was
      associated with significantly greater scores on the Expectancy scale of the
      Alcohol Craving Questionnaire (ACQ; p = .05), suggesting participants
      experiencing higher urges and desires to drink rocked to self-soothe. Second, a
      significant association was observed between a greater number of minutes spent
      rocking and lower scores on the ACQ Purposefulness subscale ( p = .03),
      indicating greater time rocking was associated with fewer urges and desires that
      are connected with the intent and plan to drink. CONCLUSION: Vestibular
      stimulation by rocking in a rocking chair may increase the ability to self
      regulate mood and substance cravings, thereby potentially reducing risk of
      relapse and recurrent chronic homelessness.

PMID- 29224462
TI  - Home Healing.

PMID- 29224461
TI  - A Qualitative Inquiry Addressing the Experience of Depression in Impoverished
      Ethnically Diverse Women: Implications for Developing a Community-Based Model.
AB  - BACKGROUND: Literature suggests that a disparity exists relative to the higher
      prevalence of depression among the population of impoverished ethnically diverse
      women, the services available, and care received resulting in a significant
      health issue for women. OBJECTIVES: An exploratory-descriptive qualitative study
      explored the experiences of depression among the population and key stakeholders
      to inform the development of a community-based program to reduce depression and
      improve the quality of life of ethnically diverse women residing in an urban
      community. DESIGN: Data were collected using focus groups and individual
      interviews with members of the population and key community representatives,
      transcribed verbatim, reviewed for accuracy, coded, and analyzed for themes.
      RESULTS: Compassion, ease, and hope emerged as the three overarching foundational
      themes. CONCLUSION: An intentional infrastructure and strategies to create an
      experience of compassion, ease, and hope appear to be essential core components
      of a successful community mental health program model for impoverished women
      experiencing depression.

PMID- 29224463
TI  - Prostatitis.
AB  - Preview Prostatitis is four diseases rather than one, and successful management
      depends on accurately classifying the condition according to systemic signs and
      symptoms and the results obtained by examination of expressed prostatic
      secretions and urine cultures. In this article, Dr Moul summarizes the
      characteristics of each type of prostatitis, with a special focus on diagnosis
      and treatment by the primary care physician.

PMID- 29224464
TI  - Myasthenia gravis.
AB  - Preview What are some simple diagnostic tests for myasthenia gravis? When is a
      patient considered too young or too old for thymectomy? How can a cholinergic
      crisis brought on by drug therapy be differentiated from an exacerbation of
      myasthenia gravis? Should prednisone be given in a high or a low dose? Dr Juhn
      addresses these and other questions.

PMID- 29224465
TI  - Osteomyelitis.
AB  - Preview Infection of bone remains difficult to treat, despite recent advances in
      antimicrobial therapy and refinements in surgical technique. To add to the
      challenge, studies have been inconclusive in establishing the best method of
      obtaining a culture specimen, comparing the effectiveness of one drug regimen
      versus another, and determining the proper duration of antibiotic therapy. Dr
      Bamberger summarizes his experience with hematogenous osteomyelitis and
      osteomyelitis secondary to a contiguous focus of infection.

PMID- 29224466
TI  - Advanced congestive heart failure.
AB  - Preview When do patients with congestive heart failure (CHF) need to be
      hospitalized? What levels of therapy should be provided in the hospital? Which
      patients should be referred for transplantation? These types of questions,
      discussed by Dr Stevenson, are the ones that need to be addressed when CHF
      reaches its advanced stages.

PMID- 29224468
TI  - Chemotherapy-induced nausea and vomiting.
AB  - Preview Modem chemotherapy provides meaningful palliation for cancer and even
      cures some forms. Unfortunately, it causes numerous adverse reactions. Nausea and
      vomiting are the most feared and debilitating for many patients; in fact, some
      patients refuse potentially beneficial chemotherapy to avoid these side effects.
      The authors discuss antiemetic drugs that are often effective in alleviating
      discomfort, especially when used in combination.

PMID- 29224467
TI  - Pneumonia in the elderly.
AB  - Preview The risks of pneumonia are greater in older patients even if they are
      relatively healthy. Which patients require hospitalization? Is the search for a
      pathogen worth the cost and effort involved? Which agents should be used for
      empirical broad- spectrum therapy? Dr McCue addresses these and other questions.

PMID- 29224469
TI  - 'The dwindles'.
AB  - Preview Elderly patients who for no immediately obvious reason lose weight,
      decline in physical and psychological function, and withdraw socially are said to
      have failure to thrive. Dr Egbert analyzes the factors that can contribute to
      this condition and offers advice on how to arrest the downward spiral in which
      these patients are caught.

PMID- 29224470
TI  - Poor sleep is related to lower general health, increased stress and increased
      confusion in elite Gaelic athletes.
AB  - OBJECTIVES: Persistent poor sleep is associated with a range of adverse health
      outcomes. Sleep is considered the main method of recovery in athletes; however,
      studies report that a significant number of athletes are getting insufficient
      sleep. The purpose of this study was to assess the sleep profiles of elite Gaelic
      athletes and to compare wellbeing in those with poor sleep and those with good
      sleep. METHODS: 69 elite Gaelic athletes completed questionnaires, including the
      Pittsburgh Sleep Quality Index (PSQI), Subjective Health Complaints Inventory
      (SHC), Nordic Musculoskeletal Questionnaire (NMQ), stress subscale of the
      Depression Anxiety Stress Scale (DASS), the tension-anxiety, anger-hostility and
      confusion-bewilderment subscales of the Profile of Mood States (POMS) as well as
      the catastrophising subscale of the Coping Strategies Questionnaire (CSQ).
      Participants were categorised into poor sleepers (PSQI >=5) and good sleepers
      (PSQI <5) and outcome measures of health and wellbeing were analysed between the
      two groups. RESULTS: 47.8% of athletes were poor sleepers. Self-reported sleep
      duration was 7.5 +/- 0.6 h per night. 63.7% of poor sleepers took >30 min to fall
      asleep, compared to 5.6% of good sleepers. Poor sleepers had significantly lower
      general health (SHC) (p = 0.029), increased stress (DASS) (p = 0.035) and
      increased confusion (POMS-subscale) (p = 0.005). There was no significant
      difference between groups for number of painful body parts (NMQ) (p = 0.052),
      catastrophising (CSQ) (p = 0.287), overall mood (POMS) (p = 0.059), or POMS
      subscales of anger (p = 0.346) or tension (p = 0.593). CONCLUSION: Nearly 50% of
      elite Gaelic athletes report poor sleep. There is a significant relationship
      between poor sleep and lower general health, increased stress and increased
      confusion, and these factors may interact with each other. Monitoring of and
      interventions to enhance sleep may be required to improve athletes' wellbeing.

PMID- 29224471
TI  - Clinical relevance of liver histopathology and different histological
      classifications of NASH in adults.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) encompasses simple
      steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and
      hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world,
      contributes to cardiovascular events and liver-related mortality and therefore
      exacts a major economic toll. Areas covered: Here we summarize what clinicians
      should know about NAFLD histopathology in adults. We report on the individual
      histological features and scoring systems of NAFLD: the NAFLD activity score
      (NAS) introduced by the NASH-Clinical Research Network, the 'Fatty Liver
      Inhibition of Progression' algorithm and Steatosis, Activity, and Fibrosis (SAF)
      score. Pros and cons of histological classifications in NASH are discussed.
      Special emphasis is given to liver histopathology in some high-risk patient
      groups, such as those with severe obesity and type 2 diabetes. Moreover, we also
      examine the relationship between liver histopathology and clinical features, and
      the impact of liver histopathology on the long-term prognosis of NAFLD. Finally,
      we propose an integrated diagnostic approach which utilizes both non-invasive
      tools and liver biopsy in those individual patients with suspected NAFLD. Expert
      commentary: Based on expert opinions, we conclude with a research agenda on NAFLD
      which focuses on the most burning topics to be addressed over the next five
      years.

PMID- 29224473
TI  - Smell impairment.
AB  - Preview People born without a sense of smell may not miss it, but those who have
      enjoyed and lost the sense certainly do. For some reason, however, the problem is
      often dismissed or not even sought during evaluation. The authors compile from
      their experience at a nasal dysfunction clinic information pertinent to primary
      care physicians and suggestions for management. They describe reversible and
      nonreversible causes of olfactory impairment and provide simplified algorithms to
      use in patient evaluation.

PMID- 29224472
TI  - Preoperative assessment of computerized tomography angiography to predict success
      for crossing long Trans-Atlantic Inter-Society Consensus D lesions using the
      optical coherence tomography catheter.
AB  - Objectives Optical coherence tomography chronic total occlusion catheter, the
      Ocelot (Avinger Inc., Redwood City, CA), has been utilized to cross Trans
      Atlantic Inter-Society Consensus D lesions. This study evaluated the preoperative
      computerized tomography angiography of chronic total occlusions in the
      superficial femoral artery to predict clinical success. Methods We reviewed all
      patients who underwent lower extremity procedures with the Ocelot catheter from
      June 2014 to August 2016. Patients who had a preoperative computerized tomography
      angiography were evaluated. Final outcomes, plaque morphology, lesion length,
      calcium surface area, lesion location, and patient characteristics were analyzed.
      Results A total of 107 patients underwent lower extremity interventions with the
      Ocelot catheter. Seventy patients had a preoperative computerized tomography
      angiography scan prior to lower extremity intervention and 77% (54) had Trans
      Atlantic Inter-Society Consensus D lesions that were crossed. Mean age was 62.8
      years and 68.6% were male. Mean chronic total occlusion length was 182.7 mm
      (170.8 mm crossed vs. 222.6 mm uncrossed, p = 0.03). Calcium distribution
      differed significantly ( p<.01): circumferential (14.8 vs. 12.5%); eccentric (85
      vs. 62.5%); and complete calcium occlusion (0 vs. 25%) for lesions that were
      crossed and uncrossed, respectively. Significant differences ( p<.0001) were
      found when calcium occlusion was less than 50% (87 vs. 31%), 51-75% (9.3 vs.
      31.2%), and 76-100% (3.7 vs. 37.5%). Total calcium length in crossed lesion was
      51.6 mm, and 92.8 mm in uncrossed lesions ( p = 0.10). No significant differences
      were noted for patient gender, occlusion location (proximal, middle, and distal
      superficial femoral artery), and kidney function. Conclusion The Ocelot catheter
      is an effective method to cross long Trans-Atlantic Inter-Society Consensus D
      lesions. Superficial femoral artery lesions longer than 17 cm and focal plaque
      morphology, specifically a total cross-sectional area of calcium and a calcium
      surface area greater than 50% were most predictive of failure to cross Trans
      Atlantic Inter-Society Consensus D superficial femoral artery lesions.
      Computerized tomography angiography is an effective tool to predict success for
      crossing chronic total occlusions using optical coherence tomography technology
      and a critical consideration for patient selection.

PMID- 29224474
TI  - Aortic valvular disease in adults.
AB  - Preview How common is sudden death in patients with aortic valvular disease? Is
      medical therapy ever helpful? When is valve replacement indicated, and what type
      of prosthesis should be used? In this article, Drs Mangion and Tighe review
      current recommendations on these problems and discuss overall management of both
      aortic stenosis and aortic regurgitation.

PMID- 29224475
TI  - Nonimmunologic adverse drug reactions.
AB  - Preview How can morbidity and mortality from adverse drug reactions be reduced
      and associated costs be minimized? What predictable reactions are commonly
      encountered in primary care? What should you watch for in terms of unpredictable
      reactions in susceptible patients? Dr Bernstein answers these and other questions
      and outlines a system for classifying adverse drug reactions.

PMID- 29224476
TI  - Complications of blood transfusion.
AB  - Preview Severe, life-threatening reactions to blood transfusion are rare but may
      be clinically similar to minor reactions, which are fairly common. The authors
      describe the manifestations of various noninfectious reactions and the laboratory
      workup necessary to discriminate among them. They also discuss the mechanisms of
      these transfusion reactions and tell how to treat and prevent them.

PMID- 29224477
TI  - The Mission Continues.

PMID- 29224478
TI  - Heatstroke and other heat-related illnesses.
AB  - Preview Victims of high heat and humidity may be young and healthy or old and
      debilitated. In either case, severe heatstroke may present a life-threatening
      situation if treatment is delayed. In this article, the authors examine the
      various therapeutic options, including physical cooling methods and supportive
      measures. They also describe therapy for the less serious summer ailments of heat
      edema, heat cramps, and heat syncope.

PMID- 29224480
TI  - Making The Grade.

PMID- 29224479
TI  - Prevention of atherosclerosis.
AB  - Preview How strong is evidence that antioxidants such as vitamins C and E and
      beta carotene prevent atherosclerosis? What effect do smoking, hypertension, and
      diabetes have on LDL cholesterol? Should we all be eating a "Mediterranean" diet?
      The authors examine the answers to these questions and make recommendations on
      the basis of current knowledge.

PMID- 29224481
TI  - Viral hepatitis.
AB  - Preview The incidence of viral hepatitis in the United States has remained fairly
      constant for several decades, despite the availability of vaccines and
      prophylactic measures and improved sanitation nationwide. However, epidemiologic
      findings, including risk factors for acquisition, are changing, probably because
      of changes in human ecology and behavior. Dr Becherer discusses this evolution in
      viral hepatitis and its effect on serologic screening.

PMID- 29224482
TI  - Common blood tests for liver disease.
AB  - Preview Detection of clinicaHy silent liver disease and determination of the
      causes of acute and chronic liver disease often require a panoply of blood tests
      and, occasionally, liver biopsy. Knowing when to order tests and which tests to
      order not only facilitates diagnosis but also leads to earlier intervention with
      appropriate therapy. This article reviews the most common blood tests for
      detecting liver disease, including viral hepatitis.

PMID- 29224483
TI  - Chronic hepatitis B.
AB  - Preview Many persons with chronic hepatitis B have no signs of the illness, and
      it is important to identify those who are at risk for progressive liver disease,
      cirrhosis, and hepatocellular carcinoma. Counseling by primary care physicians is
      recommended to help patients prevent transmission of the disease and to advise
      them of its long-term consequences. The author expresses hope that vaccination
      programs now in effect will bring this potentially lethal disease under control.

PMID- 29224484
TI  - Hepatitis C.
AB  - Preview Infection with the hepatitis C virus (HCV) is fairly common and often
      serious: Significant liver disease develops in up to 50% of cases. What are the
      risk factors for HCV infection, and how likely is it to become chronic? How
      effective is interferon therapy, and what factors influence response? What new
      treatment strategies are being evaluated? Drs Olynyk and Bacon answer these and
      other questions as they bring readers up to date on the recent explosion of
      knowledge about hepatitis C.

PMID- 29224485
TI  - Assessment of dietary factors, dietary practices and exercise on mental distress
      in young adults versus matured adults: A cross-sectional study.
AB  - : The importance of the diet in modulating mental health is uncovering as many
      dietary factors have been described to alter brain chemistry. Brain maturation
      may not complete until the age of 30 which may explain the differential emotional
      control, mindset, and resilience between young adults and matured adults. As a
      result, dietary factors may influence mental health differently in these two
      populations. OBJECTIVES: To study dietary intake, dietary practices and exercise
      in young adults (YA) (18-29 years) versus matured adults (MA) (30 years and
      older) in relation to mental distress. Another aim was to assess whether mental
      well-being potentially stimulates healthy eating, healthy practices, and
      exercising. METHODS: An anonymous internet-based survey was sent through social
      media platforms to different professional and social group networks. Best-fit
      models were constructed using the backward regression analysis to assess the
      relationship between dietary variables, exercise, and mental distress in YA
      versus MA. RESULTS: YA mood seems to be dependent on food that increases
      availability of neurotransmitter precursors and concentrations in the brain (such
      as frequent meat consumption and exercise, respectively). However, MA mood may be
      more reliant on food that increases availability of antioxidants (fruits) and
      abstinence of food that inappropriately activates the sympathetic nervous system
      (coffee, high glycemic index, and skipping breakfast). DISCUSSION AND CONCLUSION:
      Level of brain maturation and age-related changes in brain morphology and
      functions may necessitate dietary adjustments for improving mental well-being.

PMID- 29224486
TI  - Vaccination update.
AB  - Preview Although the incidence of many vaccine-preventable diseases has fallen
      dramatically, routine vaccination should be a goal of all primary care
      physicians. Childhood immunization programs alone will not eliminate these
      diseases, which are still responsible for substantial illness and death in
      infants, young adults, and the elderly. In this article, Drs Vetter and Johnson
      discuss recent developments in immunization against six common infectious
      diseases.

PMID- 29224487
TI  - Stress ulcer prophylaxis.
AB  - Preview Which critically ill patients are at increased risk for gastrointestinal
      hemorrhage from stress ulcers? Do prophylactic agents effectively reduce the
      morbidity and mortality associated with stress-related hemorrhage? The author,
      former director of a medical intensive care unit, reviews recent literature on
      stress ulcer prophylaxis and outlines the risks and benefits of providing
      preventive therapy.

PMID- 29224488
TI  - Chronic testicular pain.
AB  - Preview The complex pathways of testicular pain and referred pain are becoming
      better understood. Still, the precise physical source can be elusive, and
      advances in medical knowledge mean nothing to the patient if his pain cannot be
      relieved. Most patients can be examined and treated in the primary care office
      with readily available techniques. The authors summarize important aspects of
      evaluation and provide a practical treatment algorithm.

PMID- 29224489
TI  - Lower extremity injuries in runners.
AB  - Preview Recreational and competitive runners alike are vulnerable to lower
      extremity injuries, depending on such factors as how much ground they cover
      weekly. Knowing how to recognize and treat common running injuries is important
      to prevent further injury and severe long-term complications. Dr Wexler discusses
      the primary causes and mechanisms involved in such injuries and the appropriate
      methods for achieving optimal rehabilitation.

PMID- 29224490
TI  - Looking for Silver Linings.

PMID- 29224491
TI  - Preoperative cardiac evaluation.
AB  - Preview Medical clearance for patients who need surgery is commonly requested of
      primary care physicians. A focused evaluation of the cardiovascular and other
      major body systems is the key to assessing preoperative risk. Which diagnostic
      tools and laboratory tests are most helpful? And which findings are most
      significant? The authors answer these questions and suggest ways primary care
      doctors can help minimize complications in the perioperative period.

PMID- 29224492
TI  - Breathlessness.
AB  - Preview Dyspnea can be a terrifying sensation that requires prompt medical
      intervention. Like pain, dyspnea is not well understood and may have many causes.
      It is usually due to underlying cardiac or pulmonary diseases, but these are
      often difficult to distinguish, and they may coexist in the same patient. In this
      article, Drs Seamens and Wrenn give a comprehensive review of the condition and
      recommend diagnostic and treatment strategies.

PMID- 29224493
TI  - Screening and diagnostic breast imaging procedures.
AB  - Preview Although primary care physicians may not actually read patients'
      mammography films, they play a crucial role in detection and management of breast
      disease by abiding by screening guidelines. Patient education, reassurance, and
      guidance in decision making are all important aspects, as pointed out in this
      article. The authors describe and provide illustrations of findings on breast
      imaging studies and discuss options for follow-up.

PMID- 29224494
TI  - Hearing loss.
AB  - Preview When faced with a patient complaining of hearing loss, how do you quickly
      determine whether the situation is urgent and requires otolaryngologic referral?
      Dr Ruckenstein discusses ways to distinguish between types of hearing loss, such
      as use of simple tuning fork tests, and arrive at an appropriate individualized
      treatment plan.

PMID- 29224495
TI  - Breast cancer and primary care.

PMID- 29224496
TI  - Adjuvant systemic therapy for breast cancer.
AB  - Preview A variety of prognostic factors that offer guidelines for adjuvant
      systemic therapy must be confronted by breast cancer patients and their
      physicians. However, many questions regarding the most effective approach remain
      unanswered. In this article, the authors examine this complex field and review
      recommendations for posttreatment follow-up.

PMID- 29224497
TI  - Local and regional therapy for primary breast tumors.
AB  - Preview Few subjects in modern medicine stir the emotions and invite such
      scrutiny as breast cancer does. Important questions must be answered in its
      primary treatment: Can the breast be preserved, or is a complete mastectomy
      necessary? Should axillary node dissection be done? Will radiation therapy be
      useful? Should reconstruction be part of initial treatment? In this article, the
      authors first discuss issues that most directly affect the primary care physician
      and then review management from the perspective of the surgical oncologist.

PMID- 29224498
TI  - Hypercholesterolemia.
AB  - Preview Many patients think they have to exclude meat (beef, pork, lamb, veal,
      and processed meats) from their diet to lower their lipid levels. This
      restriction is unnecessary and deprives them of the valuable nutrients found in
      meat. Instead, they should concentrate on selecting lean cuts, controlling
      portions, and reducing consumption of high-fat foods. The authors examine the
      typical American diet and offer practical guidelines for making choices that
      include meat and reduce cholesterol levels.

PMID- 29224499
TI  - Psychosocial issues in breast cancer.
AB  - Preview No matter what the woman's age, removal of a breast or even a lump has a
      profound emotional impact. In addition to facing cancer, the patient must adjust
      to changes in her self-image. At the same time, she is often being asked to make
      stressful decisions about her treatment program from a long and growing continuum
      of options. The authors describe natural reactions in these patients, factors
      that add to their anxiety, and the important role of primary care physicians in
      support and referral.

PMID- 29224500
TI  - Transition phase clothing strategies and their effect on body temperature and 100
      m swimming performance.
AB  - OBJECTIVE: Effective warm-ups are attributed to several temperature-related
      mechanisms. Strategies during the transition phase, preceding swimming
      competition, have been shown to prolong temperature-related warm-up effects. The
      purpose of this study was to evaluate the effects of two different clothing
      strategies during the transition phase, on subsequent 100-m maximal swimming
      performance. METHODS: Nine competitive swimmers (3 female, 21 +/- 3 yrs; 6 male
      20 +/- 2 yrs, mean performance standard 702 FINA Points, mean 100-m seasons best
      time 61.54 s) completed their own 30-min individual pool warm-up, followed by 7
      min changing time and a 30-min transition phase, straight into a 100-m maximal
      effort time-trial. During the transition phase, swimmers remained seated, either
      wearing warm or limited clothing. Swimmers returned 1 week later, where clothing
      conditions were alternated. RESULTS: Post-transition phase skin and core
      temperature remained higher in the warm clothing condition compared to the
      limited clothing condition (Mean Core: 36.90 +/- 0.17 degrees C, 36.61 +/- 0.15
      degrees C, P < .01; Mean Skin: 33.49 +/- 0.59 degrees C, 31.94 +/- 0.59 degrees
      C, P < .01). One hundred-metre finish times were 0.6% faster in the warm clothing
      condition compared to the limited clothing condition (62.63 +/- 7.69 s, 63.00 +/-
      7.75 s, P < .01). CONCLUSION: Wearing warm clothing during a 30-min transition
      phase improved swimming performance by 0.6%, compared to limited clothing.

PMID- 29224501
TI  - Experimental validation of a subject-specific maximum endurance time model.
AB  - This study aimed at experimentally validating a subject-specific maximum
      endurance time (MET) model. Thirty health participants (15 males and 15 females;
      Age: mean = 21.5 years, SD = 1.6 years) volunteered to conduct an isometric elbow
      flexion task until exhaustion. The endurance times of each participant were
      measured under relative exertion levels ranging from 30% MVC (Maximum Voluntary
      Contraction) to 70% MVC at 10% intervals. Assessment of the model showed that the
      intensity-endurance time relationship for each studied individual could be well
      fitted by the subject-specific MET model (R2 > 0.89). The fatigue rates
      identified from the model fitting were normally distributed (Mean = 0.96 min-1,
      SD = 0.29 min-1). In addition, the fatigue rates of the male group were
      significantly higher than the female group. The subject-specific MET model can be
      used to predict the MET for individual workers, and further support physical task
      design, based on the fatigability data of a targeted worker population.
      Practitioner Summary: Ergonomists have extensively used MET models in physical
      fatigue assessment and physical task design. A subject-specific MET model could
      be used to predict the MET at individual levels, and also to support work design
      for a target worker population, based on the fatigability data distribution
      obtained from sampled workers.

PMID- 29224503
TI  - Cochrane's risk of bias tool in the context of psychotherapy outcome research.
AB  - The Cochrane risk of bias tool (RoB) is a widely used measure for methodological
      quality of randomized controlled trials. This paper discusses RoB's rationale and
      risk of bias domains, reports on its application in current psychotherapy meta
      analyses, and offers comments regarding the application of RoB in the context of
      psychotherapy outcome research. Our suggestions include focusing on patient's and
      therapist's expectations when judging the domain "blinding of personnel and
      participants" and paying greater attention to the domain "selective outcome
      reporting" and to matters of "treatment implementation."

PMID- 29224504
TI  - Mechanisms of carnosine-induced activation of neuronal cells.
AB  - Carnosine (beta-Ala-l-His), an imidazole dipeptide, is known to have many
      functions. Recently, we demonstrated in a double-blind randomized controlled
      trial that carnosine is capable of preserving cognitive function in elderly
      people. In the current study, we assessed the ability of carnosine to activate
      the brain, and we tried to clarify the molecular mechanisms behind this
      activation. Our results demonstrate that carnosine permeates the blood brain
      barrier and activates glial cells within the brain, causing them to secrete
      neurotrophins, including BDNF and NGF. These results point to a novel mechanism
      of carnosine-induced neuronal activation. Our results suggest that carnosine
      should be recognized as a functional food factor that helps achieve anti-brain
      aging.

PMID- 29224505
TI  - Progress in the Treatment of Hodgkin's Lymphoma.

PMID- 29224506
TI  - AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.
AB  - BACKGROUND: Patients with hemophilia A rely on exogenous factor VIII to prevent
      bleeding in joints, soft tissue, and the central nervous system. Although
      successful gene transfer has been reported in patients with hemophilia B, the
      large size of the factor VIII coding region has precluded improved outcomes with
      gene therapy in patients with hemophilia A. METHODS: We infused a single
      intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5)
      vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men
      with severe hemophilia A. Participants were enrolled sequentially into one of
      three dose cohorts (low dose [one participant], intermediate dose [one
      participant], and high dose [seven participants]) and were followed through 52
      weeks. RESULTS: Factor VIII activity levels remained at 3 IU or less per
      deciliter in the recipients of the low or intermediate dose. In the high-dose
      cohort, the factor VIII activity level was more than 5 IU per deciliter between
      weeks 2 and 9 after gene transfer in all seven participants, and the level in six
      participants increased to a normal value (>50 IU per deciliter) that was
      maintained at 1 year after receipt of the dose. In the high-dose cohort, the
      median annualized bleeding rate among participants who had previously received
      prophylactic therapy decreased from 16 events before the study to 1 event after
      gene transfer, and factor VIII use for participant-reported bleeding ceased in
      all the participants in this cohort by week 22. The primary adverse event was an
      elevation in the serum alanine aminotransferase level to 1.5 times the upper
      limit of the normal range or less. Progression of preexisting chronic arthropathy
      in one participant was the only serious adverse event. No neutralizing antibodies
      to factor VIII were detected. CONCLUSIONS: The infusion of AAV5-hFVIII-SQ was
      associated with the sustained normalization of factor VIII activity level over a
      period of 1 year in six of seven participants who received a high dose, with
      stabilization of hemostasis and a profound reduction in factor VIII use in all
      seven participants. In this small study, no safety events were noted, but no
      safety conclusions can be drawn. (Funded by BioMarin Pharmaceutical;
      ClinicalTrials.gov number, NCT02576795 ; EudraCT number, 2014-003880-38 .).

PMID- 29224507
TI  - Three Anastomotic Techniques Following Laparoscopic Rectal Cancer Resection: Our
      Experience in 155 Patients.
AB  - PURPOSE: This study aimed to assess the impact of 3 anastomotic techniques after
      laparoscopic rectal cancer resection. METHODS: In a cross-sectional study, the
      data of 155 patients who underwent surgery for rectal cancer were retrieved. An
      anastomosis was created between the left colon and anal canal with 3 different
      methods: coloanal anastomosis with protective ileostomy (group A), coloanal
      anastomosis without ostomy (group B), and delayed coloanal anastomosis (group C).
      The rates of anastomotic problems (leakage, peritonitis, and collection) were
      calculated for each treatment method. Multivariate analysis was used to verify
      the effect of anastomosis techniques. RESULTS: In 5 (3.2%) patients, peritonitis
      was observed in which 3 (9.7%) of them belonged to group B and 2 (4.1%) belonged
      to group C. In 9 (5.8%) patients, presacral collection and anastomotic leakage
      were observed; 4 (8.2%) patients belonged to group C, 4 (12.9%) patients to group
      B, and 1 (1.3%) patient to group A. Postoperative obstructions occurred in 5
      (10.2%) patients of group C, 2 (6.5%) patients of group B, and 2 (2.7%) patients
      of group A. Rectovaginal fistula was detected in 2 patients from group B.
      CONCLUSIONS: Laparoscopic surgery of rectal cancer with transanal method is
      reliable and acceptable in terms of oncologic and surgical results. This study
      showed the best results in patients who had protective ostomy.

PMID- 29224508
TI  - Linear and cyclic oligomers in polybutylene terephthalate for food contact
      materials.
AB  - Polybutylene terephthalate (PBT) is a polyester (PES) gaining more importance on
      the food contact material (FCM) market. However, little is known about the
      potential migration of PBT oligomers which are formed during polymer production.
      In this work, PBT pellets and a slotted spoon manufactured from this material by
      injection moulding were analysed on extractable oligomers and their migration
      potential into hydrophilic foods. Overall 27 oligomers (cycles and linears) could
      be identified in different extracts by HPLC-DAD/ESI-MS data, but without
      confirmation by reference substances. The oligomers were quantified by HPLC-DAD
      using bis(2-hydroxyethyl) terephthalate (BHET) as external standard and the total
      amount of oligomers isolated by reprecipitation from the pellets and the spoon
      were 0.69 and 0.71%, respectively. While cyclic oligomers made up for
      approximately 90% of the extractable oligomers, linear oligomers proved to be
      more relevant for migration into aqueous foodstuffs. Furthermore, it was shown
      that hydrolysis of oligomers can take place in water at elevated temperatures.
      Consequently, the qualitative and quantitative composition of PBT oligomers in
      aqueous foods from FCMs does not only depend on migration but also on hydrolysis.
      Migration testing of the PBT spoon under repeat use conditions with water at 100
      degrees C for 2 h resulted in 0.29 mg item-1 of linear oligomers and 0.05 mg item
      1 of the cyclic PBT dimer in the third migrate.

PMID- 29224509
TI  - Algorithms used to identify ventricular arrhythmias and sudden cardiac death in
      retrospective studies: a systematic literature review.
AB  - Drug-induced QT interval prolongation may increase the risk of sudden cardiac
      death or ventricular arrhythmias (SCD/VA), and therefore affects the safety
      profile of medications. Administrative databases can be used to inform
      pharmacoepidemiologic drug safety studies for such rare events. In order to
      compare event rates between studies, validated operational definitions of these
      events are needed. We conducted a systematic literature review in PubMed to
      identify algorithms for SCD/VA. Twenty-two studies were included in the review.
      Fifteen (68%) studies evaluated International Classification of Diseases, 9th
      revision (ICD-9) based medical data, of which six utilized a common, validated
      operational definition. This algorithm was based on principal hospitalization
      discharge diagnosis or first-listed emergency department visit diagnosis, with an
      average positive predictive value (PPV) of 85%. Four studies evaluated ICD-9
      based death data, of which three utilized a common algorithm with an average PPV
      of 88%. Further validation of ICD, 10th revision algorithms are needed. In
      conclusion, we identified a validated algorithm for SCD/VA in medical data, as
      well as in death data. As such, to ensure comparability between new research and
      the existing literature, pharmacoepidemiologic research in this area should
      utilize common, validated algorithms, such as the ones identified in our review,
      to operationally define these events.

PMID- 29224510
TI  - Researcher Self-Care in Emotionally Demanding Research: A Proposed Conceptual
      Framework.
AB  - Researchers are emotionally and psychologically affected by emotionally demanding
      research that demands a tremendous amount of mental, emotional, or physical
      energy and potentially affects or depletes the researcher's well-being. Little
      attention has been given to preparing doctoral students and novice researchers
      engaged in such studies. Four possible types of emotionally demanding research
      experiences are presented: sensitive issues, personal trauma previously
      experienced, experience of traumatic life events during research, and unexpected
      events that arise during research in what was previously not identified as a
      sensitive issue. The need for self-care is highly relevant to each type, despite
      their different impacts on researcher well-being. This conceptual article
      furthers conversation in the field about how researchers and educators can
      address the need for self-care to prepare novice researchers and proposes a
      conceptual framework for researcher self-care in emotionally demanding research,
      with an aim for future empirical study.

PMID- 29224511
TI  - Measuring and improving student engagement in clinical training.
AB  - PURPOSE: Volunteer service learning activities, including Student Run Clinics
      (SRCs), are becoming an increasingly popular extracurricular component of medical
      education. While there are reports that student clinicians generally enjoy their
      educational experiences at SRCs, it is not understood how to optimize and measure
      student engagement in them. To identify key drivers of student engagement a tool
      was created to measure volunteer experience at the Crimson Care Collaborative
      (CCC), a primary care SRC. METHODS: CCC volunteers were asked to complete an
      online engagement survey. Cross-sectional survey data were collected for 149 CCC
      volunteers (53% response rate). RESULTS: Multivariate linear regression showed
      that overall 'likelihood to recommend CCC to a friend' was significantly
      associated with students' perception of the clarity of their role within the
      clinic, frequency of interprofessional interactions, and overall quality of
      medical education. Students who volunteer more frequently and for longer periods
      of time had higher engagement scores. CONCLUSIONS: Measuring engagement is
      feasible in volunteer settings. Engagement appears to be dependent on both
      structural and experiential components. Easily modifiable components of job
      design (role definition, expected frequency of volunteering), are key drivers of
      volunteer engagement.

PMID- 29224502
TI  - Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma.
AB  - BACKGROUND: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has
      been approved for relapsed and refractory Hodgkin's lymphoma. METHODS: We
      conducted an open-label, multicenter, randomized phase 3 trial involving patients
      with previously untreated stage III or IV classic Hodgkin's lymphoma, in which
      664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and
      dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin,
      vinblastine, and dacarbazine (ABVD). The primary end point was modified
      progression-free survival (the time to progression, death, or noncomplete
      response and use of subsequent anticancer therapy) as adjudicated by an
      independent review committee. The key secondary end point was overall survival.
      RESULTS: At a median follow-up of 24.6 months, 2-year modified progression-free
      survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval
      [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference
      of 4.9 percentage points (hazard ratio for an event of progression, death, or
      modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths
      with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95%
      CI, 0.45 to 1.18]; P=0.20)  [corrected]. All secondary efficacy end points
      trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving
      A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile
      neutropenia was lower among the 83 patients who received primary prophylaxis with
      granulocyte colony-stimulating factor than among those who did not (11% vs. 21%).
      Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43%
      of patients in the ABVD group; 67% of patients in the A+AVD group who had
      peripheral neuropathy had resolution or improvement at the last follow-up visit.
      Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients
      receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred
      during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and
      11 of 13 in the ABVD group were associated with pulmonary-related toxicity.
      CONCLUSIONS: A+AVD had superior efficacy to ABVD in the treatment of patients
      with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower
      combined risk of progression, death, or noncomplete response and use of
      subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals
      and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT
      number, 2011-005450-60 .).

PMID- 29224512
TI  - Analytical validation of cardiac troponin I assays in horses.
AB  - Human cardiac troponin I (cTnI) assays have been used in equine medicine, often
      without prior analytical validation for equine use. In the absence of appropriate
      validation, the clinical significance of assay results is uncertain and can lead
      to misdiagnosis. We followed the American Society for Veterinary Clinical
      Pathology guidelines and investigated linearity, precision, limit of
      quantification (LoQ), and comparative recovery for 6 commercial cTnI assays
      developed for use in human medicine. Clinically acceptable linearity was observed
      in assays A-D, whereas assay E did not detect equine cTnI in any sample.
      Comparative recovery revealed 1-3-fold differences between assay results, and low
      analyte recoveries (2.2-3.4%) were observed in assay F. Precision was
      investigated in assays A and B, and found to be within acceptable limits. The LoQ
      was 1.53 ng/L for assay A, and 0.031 ug/L for assay B. Assays A and B performed
      within clinically acceptable limits and were deemed suitable for use in equine
      medicine. Assays C and D did not undergo full validation but had acceptable
      linearity, which demonstrates their potential for use in equine medicine. Assays
      E and F are unsuitable for use in horses given issues with detection of equine
      cTnI. The variability in results between assays indicates that reference
      intervals and cutoffs for diagnostic decision-making are assay specific and
      should be established prior to adoption by diagnostic laboratories.

PMID- 29224513
TI  - Infectious necrotic hepatitis caused by Clostridium novyi type B in a horse: case
      report and review of the literature.
AB  - A 14-y-old bay Quarter Horse gelding was presented with progressive neurologic
      signs, elevated rectal temperature, and icterus for 3 d prior to death.
      Postmortem examination revealed icterus, large amounts of serosanguineous fluid
      in the abdominal cavity, widespread petechiae and ecchymoses in several organs,
      and a large, pale, and well-demarcated focus of necrosis in the liver.
      Histologically, there was coagulative necrosis surrounded by a rim of
      inflammatory cells and large numbers of gram-positive rods, which were identified
      as Clostridium novyi by immunohistochemistry. Liver samples tested by PCR were
      positive for C. novyi type B flagellin and alpha toxin genes, but negative for
      Clostridium haemolyticum and other clostridia. Based on postmortem findings and
      ancillary tests, a definitive diagnosis of infectious necrotic hepatitis (INH)
      was made. Mostly a disease of ruminants, also known as black disease, INH has
      rarely been reported in horses, and a definitive etiologic diagnosis has not been
      achieved previously; the etiology of all cases reported to date was identified as
      C. novyi but the type was not determined. Animals are predisposed to clostridial
      hepatitis when hepatic anaerobiosis is established. Such conditions allow
      germination and proliferation of bacterial spores, resulting in production and
      release of toxins. INH, caused by C. novyi type B, and bacillary hemoglobinuria,
      caused by C. haemolyticum, are mechanistically and pathologically almost
      indistinguishable. Because these 2 microorganisms are closely related,
      differentiation requires molecular tools.

PMID- 29224514
TI  - The similar to RCD-one 1 protein SRO1 interacts with GPX3 and functions in plant
      tolerance of mercury stress.
AB  - Heavy metals in the environment are one of the major limiting factors affecting
      plant growth and development. However, the mechanisms of the heavy metal-induced
      physiological processes remain to be fully dissected. Here, we explored that SRO1
      can physically interact with Glutathione Peroxidase 3 (GPX3) in Arabidopsis.
      Under Hg treatment, similar to the sro1, the growth of the gpx3/sro1 was
      repressed more seriously and the number of true leaves was more reduced and
      etiolated than that of the wild type and gpx3 plants. The electrolyte leakage
      rates showed that cell membrane integrity in gpx3/sro1 was damaged more severely
      than in the wild type and gpx3 mutant. The Real-time PCR results have shown that
      the expression of the APX1 and CAT3 was reduced under mercury stress in the sro1
      and sro1/gpx3. Our results suggested that the combination of the SRO1 and GPX3
      may be contributed to plant response to mercury stress by regulating ROS
      intracellular oxidative homeostasis.

PMID- 29224515
TI  - Return to Babel.
AB  - End of life and beginning of life are surprisingly similar. What can we learn
      about the value and nature of our lives from dementia and aging?

PMID- 29224516
TI  - Eternal Life.

PMID- 29224517
TI  - A day in the life of a Mayo chaplain ....

PMID- 29224518
TI  - Grief as a Mystical Journey: Fowler's Stages of Faith Development and Their
      Relation to Post-Traumatic Growth.
AB  - This paper explores the relationship between embedded theological assumptions and
      the ways in which one copes with loss and bereavement. Based on James Fowler's
      research on Stages of Faith Development, the paper examines common Western psycho
      spiritual beliefs related to loss, trauma, and grief, and proposes that profound
      loss experiences have the potential to lead the griever to a shift in theological
      thinking. It addresses the ways in which a "crisis of faith" triggered by loss or
      trauma prompts the questioning of closely-held beliefs, which can lead to an
      expanded spiritual perspective that can be beneficial to the healing process.

PMID- 29224519
TI  - Frames for the Future: Developing Continuing Education & Professional Development
      Programs for Spiritual Care Practitioners: A Perspective from Victoria,
      Australia.
AB  - This article examines the educational issues in ongoing professional education
      for spiritual care practitioners. A meta-evaluation of registration and
      evaluation data over four years (between 2013 and 2016) of one such monthly
      program conducted by Spiritual Health Victoria (Australia) will be examined.
      Recommendations are made to support healthcare managers and spiritual care
      educators in designing and developing continuing education programs for spiritual
      care practitioners in a variety of other professional health and care contexts.

PMID- 29224520
TI  - The Role of the Pastoral Practitioner in Health Outcomes and Wellbeing During
      Acute Illness: Exploring the Patient Experience of a Pastoral Visit.
AB  - The role of the pastoral practitioner is embedded in many health care services
      and organizations. Despite this, there is little evidence to describe the impact
      of this role on patient outcomes, in particular how visits by a pastoral
      practitioner influence patient healing and recovery. This paper describes a small
      study that explored the patient experience of pastoral practitioner visits in an
      acute care facility.

PMID- 29224521
TI  - Towards a faith-based understanding of moral injury.
AB  - In recent years, the issue of moral injury (MI) has garnered considerable
      attention, especially as related to the military experiences of Service Members
      and Veterans. This brief communication is intended to provide an overview of
      Christian, Jewish, and Islamic understandings of MI. The intent is to draw
      attention to a faith-based etiology for MI, thereby facilitating dialogue and
      discussion on the relevance of spiritual and pastoral care to supporting those
      affected by MI.

PMID- 29224522
TI  - The Journal of Pastoral Care & Counseling Quiz.

PMID- 29224523
TI  - The Effect of Religious Involvement on Life Satisfaction among Korean Christians:
      Focused on the Mediating Effect of Spiritual Well-Being and Self-Esteem.
AB  - The present study examined the relationship between two categories of religious
      involvement, namely religious belief and religious behavior, and life
      satisfaction among Korean Christians (N = 278) with spiritual well-being and self
      esteem as potential mediators in this relationship by using structural equation
      modeling (SEM). The results supported the full mediated structural model and
      indicated that religious belief had a significant indirect effect on life
      satisfaction through the mediators, spiritual well-being and self-esteem.
      Religious behavior did not have an indirect or direct effect on life satisfaction
      among Korean Christians. The significance, implications, and limitations of the
      study were discussed.

PMID- 29224524
TI  - Cultural Resilience.

PMID- 29224525
TI  - Assessing Transcendental Experiences vs Mental Illnesses.
AB  - In our experience, being able to differentiate between mental illness and
      transcendent experiences has led patients to remain engaged in treatment. This is
      important since those who have experienced religious preoccupation are the least
      likely to seek out mental health care. We have developed a "Transcendent
      Assessment Tool" to assist clinicians and clients in discerning whether an
      experience is a delusion or part of a transcendent experience.

PMID- 29224526
TI  - Handling Stereotypes of Religious Professionals: Strategies Hospice Chaplains Use
      When Interacting with Patients and Families.
AB  - Stereotypes of religious professionals can create barriers for those who provide
      spiritual/pastoral care. Through interviews and journal entries, hospice
      chaplains ( n = 45) identified the following stereotypes that affected their
      work: chaplains as people whom others try to impress, who only talk about
      spiritual and religious topics, who are male, and who try to convert others.
      Participants reported using a variety of communication strategies to counteract
      stereotypes and make meaningful connections with the people they serve.

PMID- 29224529
TI  - Hyperprolactinemia.
AB  - Preview An elevated serum prolactin level has many causes, including pituitary
      tumors, hypothalamic disease, and certain drugs. Dr Kaye reviews the various
      causes of hyperprolactinemia and discusses evaluation and treatment options for
      this common metabolic disorder.

PMID- 29224527
TI  - Church Services in a Complex Continuing Care Hospital: Why Bother?
AB  - This research aimed to explore patient motivation for attending hospital-run
      church services in a complex continuing care hospital setting, as well as the
      perceived spiritual benefits as categorized by Fitchett's 7 * 7 Model for
      Spiritual Assessment. Invitations to participate in one-to-one interviews were
      offered to all patient attendees at both an ecumenical and a Roman Catholic
      service over the course of several weeks. We collected 20 interviews before
      performing a qualitative analysis, at which point we determined that saturation
      of content had been reached. The key findings were that participants identified
      the strongest perceived benefits in Experiences and Emotions, and Rituals and
      Practice, suggesting that access to the ritual of Sunday church services
      contributes meaningfully to participants' coping strategies and overall quality
      of life.

PMID- 29224530
TI  - Functional assessment in older patients.
AB  - Preview Practical assessment of the functional and support factors affecting
      quality of life in older patients should be an integral part of medical
      management. This approach allows physicians to focus on remediable problems that
      compromise patients' daily functioning and may hinder them from living
      independently. In this overview, Drs Paist and Jafri discuss the key concerns of
      functional assessment and present an illustrative case of an 86-year-old man with
      multiple problems.

PMID- 29224531
TI  - Recognizing glaucoma.
AB  - Preview A better understanding of the pathophysiology of glaucoma, a principal
      cause of blindness in the United States, has resulted in refined methods of
      diagnosis and treatment. The most common form of the disease in adults- primary
      open-angle glaucoma- is slowly progressive and initially asymptomatic, and its
      diagnosis relies on regular screening procedures. In this article, the authors
      review management of the various types of glaucoma, including emergency treatment
      of angle-closure disease.

PMID- 29224532
TI  - Geriatric issues.

PMID- 29224533
TI  - Acute epistaxis.
AB  - Preview Acute anterior nosebleeds are frightening because bleeding is often so
      copious and seemingly unstoppable. But, ironically, this type is usually less
      severe than posterior epistaxis, in which blood may run briskly but unseen down
      the throat. The choice among the many treatment methods available depends on the
      source and cause of epistaxis. The authors present a methodical approach to
      patient evaluation and describe the best therapy for various situations.

PMID- 29224535
TI  - Do We Really Have A Doctor Glut?

PMID- 29224534
TI  - Ready, set, go!
AB  - Preview Event and team physicians reap many rewards working with highly skilled
      and motivated athletes. The rewards are greatest when problems are anticipated
      and prevented. As discussed by Drs Leonard and Townsend, the key to success for
      both physicians and athletes is careful and specific planning. One might say that
      the Boy Scout motto, "Be prepared," cannot be overemphasized in this setting.

PMID- 29224536
TI  - Otitis externa.
AB  - Preview Although mild cases of otitis externa often respond quickly to
      appropriate therapy, primary care physicians need to be alert to more severe
      infection, particularly in diabetic and immunocompromised patients. In these
      cases, uncomplicated infection may progress to deep invasion of bone and become
      potentially fatal if cranial nerves are affected. Prompt referral to an
      otolaryngologist is recommended.

PMID- 29224537
TI  - Urinary incontinence.
AB  - Preview Many older patients with urinary incontinence hesitate to tell their
      healthcare providers, and even if they do, the condition may not be properly
      assessed or treated. As a result, patients may restrict or even totally avoid
      social activities. In this article, Drs Yim and Peterson stress the need for
      greater awareness of the problem and describe basic types of incontinence,
      diagnostic studies, and treatment options that can improve the quality of life of
      affected patients.

PMID- 29224538
TI  - Brain failure in older patients.
AB  - Preview Abrupt changes in consciousness or attention span are not normal at any
      age. No healthcare professional would ignore these signs of delirium in a 30-year
      old, but the authors note that such changes are often ignored (or worse, treated
      with tranquilizers) in older patients. A gradually decreasing ability to reason,
      to remember, and to exercise appropriate judgment is not normal either. The
      authors describe careful evaluation of patients exhibiting such changes, with
      particular emphasis on seeking potentially reversible causes.

PMID- 29224539
TI  - Use of urokinase in pregnancy.
AB  - Preview Urokinase thrombolytic therapy has had limited use in pregnancy because
      of concerns about teratogenic effects and potential bleeding. However, reports of
      successful use are encouraging. Here, the authors describe their experience in
      effective use of low-dosage urokinase to treat deep venous thrombosis in two
      pregnant women.

PMID- 29224540
TI  - The aging process.
AB  - Preview Although no one theory on aging explains satisfactorily why or how this
      process occurs, we know that aging causes physiologic changes and a progressive
      decline of functional organ reserve. The implications of these changes are
      increasingly important as the elderly segment of the population grows. In this
      article, Dr Troncale discusses the aging process and its effects, particularly in
      regard to drug therapy.

PMID- 29224541
TI  - Ebola virus disease.
AB  - Preview For many Americans, the movie Outbreak was our first introduction to
      Ebola virus. However, we may have dismissed it as mere cinematic sensationalism
      until the deadly outbreak of Ebola virus disease occurred in Zaire last May.
      Fortunately, few cases have been seen in the United States, but primary care
      physicians should nonetheless be aware of the signs and symptoms. In this
      article, Dr Sodhi reviews the history of the virus, manifestations of the
      infection, and appropriate management and preventive measures.

PMID- 29224542
TI  - Hepatotoxic effects of tuberculosis therapy.
AB  - Preview The recent resurgence of tuberculosis in the United States- fueled in
      part by its increased incidence among those infected with HIV, substance abusers,
      and recent immigrants- necessitates a fresh look at tuberculosis therapy.
      Management is tricky because the first-line antituberculosis drugs can be
      hepatotoxic, particularly in the presence of underlying liver disease. Patient
      compliance and close follow-up are essential to achieving a cure while avoiding
      the pitfalls. Dr Ali describes some of the most commonly used antituberculosis
      drugs, discusses ways to avoid or minimize hepatotoxicity, and presents a useful
      algorithm.

PMID- 29224543
TI  - Vancomycin-resistant enterococci.
AB  - Preview New antimicrobial pathogens resistant to vancomycin are wreaking havoc in
      medical centers throughout the nation. Their tendency to colonize or infect
      severely ill, hospitalized patients who have undergone invasive procedures and
      received prolonged courses of antimicrobial therapy is alarming. The most potent
      weapon in the physician's arsenal against these enemies is familiarity with their
      key features, with the guidelines for prudent use of drug therapy, and with the
      precautionary measures necessary to limit contact and spread.

PMID- 29224544
TI  - Interstitial cystitis.
AB  - Preview Although it's not a malignant or infectious condition, interstitial
      cystitis can be as disabling and sometimes even more difficult to manage. Many
      women undergo ineffective gynecologic surgery, and some men have inappropriate
      transurethral prostatectomy in a desperate attempt to subdue their pain. The
      authors provide tips for primary care physicians on making a presumptive
      diagnosis and suggest symptomatic relief methods to try before referral.

PMID- 29224545
TI  - Bringing your office into the computer age.

PMID- 29224546
TI  - Management of depression.
AB  - Preview Although depression is an eminently treatable illness, it is often
      overlooked. When it is detected, it can be difficult to manage because of the
      adverse effects of antidepressant therapy. Dr Kuzel presents recommendations for
      better detection and treatment of this common clinical problem in the primary
      care setting.

PMID- 29224547
TI  - Helping Smokers Quit.

PMID- 29224548
TI  - Nasogastric and feeding tubes.
AB  - Preview The authors' experience in a radiology department suggested to them that
      there is a wide range of beliefs among practitioners regarding proper placement
      of nasogastric and feeding tubes. Improper positioning can cause serious
      problems, as they explain. Indications for different tube positions,
      complications of incorrect tube placement, and directions for proper positioning
      are discussed and illustrated.

PMID- 29224549
TI  - Why we need a golden rule for peer review.

PMID- 29224552
TI  - Factors Influencing the Eating Practices of Hospital Nurses During Their Shifts.
AB  - The purpose of this study was to identify factors influencing hospital nurses'
      dietary practices during their shifts. Semistructured interviews grounded in the
      Social Ecological Model focused on individual, interpersonal, organizational, and
      public policy factors affecting intake. Responses from 20 female nurses were
      qualitatively coded and categorized based on common themes. Four major themes
      emerged: occupational characteristics, hesitation to take breaks, influence of
      unhealthy food, and organizational and industry policies. Of note, nurses'
      perceived inability to take breaks was due to patient load, unpredictability of
      patient needs, reluctance to burden other nurses, a tendency to prioritize
      patient care over self-care, and the repercussions of working longer hours to
      complete work. Other influential factors included the presence of unhealthy food
      options, regulations restricting nurses' ability to eat and drink in the
      workplace, and the need for more staff. Multilevel interventions are necessary to
      ensure nurses take appropriate meal breaks and maintain satisfactory dietary
      habits.

PMID- 29224553
TI  - Arteriosclerosis obliterans.
AB  - Preview With improvement in noninvasive assessment methods in recent years,
      therapeutic options for arteriosclerosis obliterans have expanded. Much can be
      done to control symptoms of intermittent claudication and improve overall
      functioning before angioplasty or bypass surgery need be considered. Here Drs Ku
      and Nagler discuss the options in evaluation and management of this costly
      medicosocial problem.

PMID- 29224554
TI  - Anorectal disorders.
AB  - Preview Both patients and physicians tend to ascribe all anorectal symptoms to
      hemorrhoids, but many are caused by other common conditions. Anal fissure,
      perianal abscess, pruritus ani, and condylomata acuminata that have reached a
      large size also cause considerable discomfort. Dr Metcalf summarizes identifying
      characteristics of the disorders, treatments that can be performed in an office
      visit, and circumstances that may warrant more extensive surgical procedures.

PMID- 29224555
TI  - Fingertip and nail bed injuries.
AB  - Preview A moment of distraction is all it takes for a kitchen knife, power tool,
      or piece of industrial or farm equipment to crush or slice off a fingertip. In
      children, slamming doors, bicycle chains, and folding chairs are common threats
      to tiny fingers and nails. The authors, who are plastic surgeons, explain that an
      understanding of fingertip anatomy and basic surgical skills are needed to treat
      these wounds. They describe the most common types of fingertip injuries,
      assessment of the damage, and options for surgical treatment.

PMID- 29224556
TI  - Inflammatory diseases of the colon.
AB  - Preview Symptoms of inflammatory diseases of the colon can be numerous and
      varied, ranging from the slight rectal bleeding of proctitis to the abdominal
      tenderness, bloody diarrhea, fever, dehydration, and orthostasis of fulminant
      colitis. The authors discuss how symptoms and other findings guide the diagnosis
      of ulcerative colitis, Crohn's disease, infectious colitis, colonic ischemia and
      vasculitis, and other types of colitis. They also summarize treatment methods.

PMID- 29224557
TI  - Functional colonic and anorectal disorders.
AB  - Preview They are problems no one wants to talk about. But like most disorders,
      constipation and fecal incontinence probably won't disappear by being ignored. To
      discover the specific type of problem present and the possible causes, physicians
      must overcome reluctance to discuss defecation disorders and pursue thorough
      history taking. Dr Rao summarizes methods for determining the underlying cause.
      In addition, he describes approaches to management that are often successful and
      help restore confidence and dignity to patients.

PMID- 29224558
TI  - Colorectal neoplasms.
AB  - Preview Colorectal neoplasms occur in many forms, but two are of primary clinical
      significance to physicians-adenoma and adenocarcinoma. Among the challenges these
      lesions present are accurate diagnosis, effective therapy, practical and
      affordable screening and surveillance, and primary prevention. Of key importance
      in designing workable management strategies is identification of factors that
      define higher-risk patient groups.

PMID- 29224559
TI  - Vaccination update.
AB  - Preview Inadequate immunization of infants, children, and persons at high risk
      for certain infectious diseases continues to result in excess deaths every year
      in the United States. With improved vaccination rates, many of these deaths could
      be prevented. This article focuses on current immunization guidelines and recent
      developments in the battle against seven vaccine-preventable diseases.

PMID- 29224560
TI  - Congestive heart failure.
AB  - Preview Congestive heart failure (CHF) is a common and serious problem, and its
      diagnosis and treatment should not be the exclusive province of the cardiologist.
      Primary care physicians can very adequately manage most cases in a cost-effective
      manner. In this article, Dr Seager gives guidelines for a standard approach to
      CHF and discusses special management problems, including treatment failures.

PMID- 29224561
TI  - Chronic schizophrenia.
AB  - Preview Perhaps one fourth of patients with schizophrenia respond only partially
      to standard neuroleptic therapy. Until recently, the only pharmacologic option
      for such patients was adjunctive treatment with other psychotropic drugs. Now two
      newer drugs-clozapine and risperidone-offer hope to patients with treatment
      resistant schizophrenia. This article provides an up-to-date look at effective
      treatment of this troubling disorder.

PMID- 29224562
TI  - Recurrent corneal erosions.
AB  - Preview Recurrent corneal erosion presents a diagnostic challenge because of its
      similarity to other common corneal conditions, such as herpetic ulcer. Primary
      care physicians can make the diagnosis (and earn the gratitude of their patients)
      if they have a high index of suspicion, take a careful history, and look for
      objective findings. In this article, the authors focus on the role of the primary
      care physician in the diagnosis and treatment of post-traumatic recurrent corneal
      erosions.

PMID- 29224563
TI  - Glad to Be Alive.

PMID- 29224564
TI  - Fetal alcohol syndrome.
AB  - Preview Most women know that alcohol consumption and pregnancy do not mix. But
      some pregnant women choose to drink anyway, and the effects on the fetus can be
      devastating. In this article, Dr Bratton discusses the clinical manifestations
      and economic impact of fetal alcohol syndrome and emphasizes the importance of
      screening for alcohol use and counseling against it during routine prenatal care.

PMID- 29224566
TI  - Diseases of the colon.

PMID- 29224565
TI  - Pitfalls in HIV testing.
AB  - Preview Inaccurate results on HIV tests are rare, but they do occur. Therefore,
      it is important that primary care physicians understand the laboratory techniques
      involved. Which assays are used for detection of the virus? How are results of
      such tests interpreted? What factors cause false-positive and falsenegative
      results? Drs Cordes and Ryan answer these questions and clarify the uncertainty
      surrounding HIV testing.

PMID- 29224568
TI  - Internal herniation through lesser omentum hiatus and gastrocolic ligament with
      malrotation: a case report.
AB  - BACKGROUND: Internal herniation through lesser omentum hiatus and gastrocolic
      ligament with malrotation is extremely rare. This type of internal hernia has
      rarely been described before. Preoperative diagnosis is difficult and prone to
      misdiagnosis. CASE PRESENTATION: A 38-year-old Chinese woman was an emergency
      admission to our hospital with a sudden onset of acute epigastralgia for the past
      14 hours. We made a presumptive diagnosis of gastrointestinal perforation and
      septic shock. Due to the acute onset and rapid progress, she received timely
      surgical treatment. During operation, we observed that her small intestine
      herniated into the hepatogastric ligament and ligamentum gastrocolicum hiatus
      accompanied with intestinal malrotation that resulted in internal hernia. We
      found a diverticulum of approximately 3.0 * 6.0 cm sited at a distance of 80 cm
      from the ileocecal intestine. We resected the strangulated intestinal loop and
      the diverticulum, performed an appendicectomy, and closed the ligamentous
      fissure. Postoperation, she recovered smoothly, without any complications, and
      was discharged on day 6. CONCLUSIONS: A case of internal hernia formation is
      quite rare; accurate preoperative diagnosis and timely surgery are essential
      because it can cause strangulation of the ileus. However, the incidence of this
      internal herniation is low and preoperative diagnosis is difficult. An accurate
      preoperative diagnosis of internal hernia is still a challenge.

PMID- 29224569
TI  - Humanitarian and primary healthcare needs of refugee women and children in
      Afghanistan.
AB  - This Commentary describes the situation and healthcare needs of Afghans returning
      to their country of origin. With more than 600,000 Afghans returned from Pakistan
      and approximately 450,000 Afghans returned from Iran in 2016, the movement of
      people, which has been continuing in 2017, presents additional burden on the weak
      health system and confounds new health vulnerabilities especially for women and
      children. Stewardship and response is required at all levels: the central
      Ministry of Public Health, Provincial Health Departments and community leaders
      all have important roles, while continued support from development partners and
      technical experts is needed to assist the health sector to address the emergency
      and primary healthcare needs of returnee and internally displaced women, children
      and families.

PMID- 29224570
TI  - Mapping the evidence on pharmacological interventions for non-affective psychosis
      in humanitarian non-specialised settings: a UNHCR clinical guidance.
AB  - BACKGROUND: Populations exposed to humanitarian emergencies are particularly
      vulnerable to mental health problems, including new onset, relapse and
      deterioration of psychotic disorders. Inadequate care for this group may lead to
      human rights abuses and even premature death. The WHO Mental Health Gap Action
      Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian
      settings (mhGAP-HIG), provides guidance for management of mental health
      conditions by non-specialised healthcare professionals. However, the
      pharmacological treatment of people with non-affective psychosis who do not
      improve with mhGAP first-line antipsychotic treatments is not addressed. In order
      to fill this gap, UNHCR has formulated specific guidance on the second-line
      pharmacological treatment of non-affective psychosis in humanitarian, non
      specialised settings. METHODS: Following the Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) methodology, a group of
      international experts performed an extensive search and retrieval of evidence on
      the basis of four scoping questions. Available data were critically appraised and
      summarised. Clinical guidance was produced by integrating this evidence base with
      context-related feasibility issues, preferences, values and resource-use
      considerations. RESULTS: When first-line treatments recommended by mhGAP (namely
      haloperidol and chlorpromazine) are not effective, no other first-generation
      antipsychotics are likely to provide clinically meaningful improvements.
      Risperidone or olanzapine may represent beneficial second-line options. However,
      if these second-line medications do not produce clinically significant beneficial
      effects, there are two possibilities. First, to switch to the alternative
      (olanzapine to risperidone or vice versa) or, second, to consider clozapine,
      provided that specialist supervision and regular laboratory monitoring are
      available in the long term. If clinically relevant depressive, cognitive or
      negative symptoms occur, the use of a selective serotonin reuptake inhibitor may
      be considered in addition or as an alternative to standard psychological
      interventions. CONCLUSIONS: Adapting scientific evidence into practical guidance
      for non-specialised health workers in humanitarian settings was challenging due
      to the paucity of relevant evidence as well as the imprecision and inconsistency
      of results between studies. Pragmatic outcome evaluation studies from low
      resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance
      is based on best available evidence and can help to address the compelling issue
      of undertreated, non-affective psychosis in humanitarian settings.

PMID- 29224571
TI  - 'Worried to death': the assessment and management of anxiety in patients with
      advanced life-limiting disease, a national survey of palliative medicine
      physicians.
AB  - BACKGROUND: Anxiety adversely affects quality of life and is common in adults
      with advanced life-limiting disease. There are no UK-wide guidelines on the
      assessment and management of anxiety in this specific population and there is
      little evidence regarding drug treatments. This study aimed to explore how
      palliative care physicians assess and manage anxiety in their patients, and to
      identify barriers encountered. METHODS: A cross-sectional survey was undertaken
      of all physicians working in specialist palliative care in the UK who were
      members of the Association for Palliative Medicine. This was conducted in
      February 2014 using an online questionnaire. RESULTS: The response rate was 23%
      (230/980) and 61% of respondents were consultants. Most did not use tools to
      screen for anxiety (87%) and almost all used the clinical interview to diagnose
      anxiety (99%). Only 8% used psychiatric criteria. Most physicians reported
      difficulties managing anxiety (93%). Only 33% thought they had adequate training
      in this area. Most had difficulty accessing psychological and/or psychiatric
      services (71%, 64% respectively). The majority used a combination of
      pharmacological and non-pharmacological treatments for anxiety. The most
      frequently prescribed first-line medications for patients with a prognosis of
      days to weeks were benzodiazepines (93%), usually lorazepam. The use of
      benzodiazepines over antidepressants was statistically significant (p < 0.001).
      For patients with a prognosis of months, antidepressants were most frequently
      prescribed first-line (60%), significantly more than benzodiazepines (p < 0.001).
      However, benzodiazepine use was still common in this prognostic group with 47%
      prescribing it first-line, sometimes in combination with an antidepressant.
      CONCLUSION: This is the first national survey on the assessment and management of
      anxiety in palliative care. Findings demonstrate the infrequent use of screening
      tools, variation in prescribing practice, potentially inappropriate use of
      benzodiazepines for patients with a prognosis of months, training gaps and poor
      access to psychological and psychiatric services in the UK. This highlights the
      need for formal training, further research into the pharmacological management of
      anxiety in this population and evidence-based national guidance to support
      clinical decision-making and service development.

PMID- 29224572
TI  - Individual, collective, and transgenerational traumatization in the Yazidi.
AB  - In recent years, Islamic terrorism has manifested itself with an unexpectedly
      destructive force. Despite the fact that Islamic terrorism commences locally in
      most cases, it has spread its terror worldwide. In August 2014, when troops of
      the self-proclaimed 'Islamic State' conquered areas of northern Iraq, they turned
      on the long-established religious minorities in the area with tremendous
      brutality, especially towards the Yazidis. Vast numbers of men were executed, and
      women and children were abducted and willfully subjected to sexual violence. With
      the aim of systematic destruction of the Yazidi community, the religious minority
      was to be eliminated and the will of the victims broken. The medical and mental
      health issues arising from the combination of subjective, collective, and
      cultural traumatization, as well as the subsequent migrant and refugee crisis,
      are therefore extraordinary and require novel and wise concepts of integrated
      medical care.

PMID- 29224573
TI  - Brain glutamate in medication-free depressed patients: a proton MRS study at 7
      Tesla.
AB  - BACKGROUND: The possible role of glutamate in the pathophysiology and treatment
      of depression is of intense current interest. Proton magnetic resonance
      spectroscopy (MRS) enables the detection of glutamate in the living human brain
      and meta-analyses of previous MRS studies in depressed patients have suggested
      that glutamate levels are decreased in anterior brain regions. Nevertheless, at
      conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to
      separate glutamate from its metabolite and precursor, glutamine, with the two
      often being measured together as Glx. In contrast, MRS at 7 T allows clear
      spectral resolution of glutamate and glutamine. METHOD: We studied 55 un
      medicated depressed patients and 50 healthy controls who underwent MRS scanning
      at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and
      putamen (PUT). Neurometabolites were calculated using the unsuppressed water
      signal as a reference. RESULTS: Compared with controls, depressed patients showed
      no significant difference in glutamate in any of the three voxels studied;
      however, glutamine concentrations in the patients were elevated by about 12% in
      the PUT (p < 0.001). CONCLUSIONS: The increase in glutamine in PUT is of interest
      in view of the postulated role of the basal ganglia in the neuropsychology of
      depression and is consistent with elevated activity in the descending cortical
      glutamatergic innervation to the PUT. The basal ganglia have rarely been the
      subject of MRS investigations in depressed patients and further MRS studies of
      these structures in depression are warranted.

PMID- 29224574
TI  - Joint associations of dietary pattern and television viewing with CVD risk
      factors among urban men and women in China: a cross-sectional study.
AB  - The purpose of this study was to investigate the joint associations of dietary
      pattern and television viewing with risk factors of CVD among urban adults in
      China. A community-based cross-sectional study was conducted among urban adults
      in Nanjing, China. Five dietary patterns were identified based on a FFQ.
      Television time was obtained from a standard questionnaire and further classified
      into two categories (<=7, >7 h/week). Multiple logistic regression was used to
      calculate the OR and 95 % CI for the separate and joint associations of dietary
      patterns and television viewing with CVD risk factors. Compared with other
      dietary patterns, participants who followed the healthy traditional pattern had a
      lower likelihood of abdominal obesity (AO) (OR 0.52; 95 % CI 0.41, 0.67).
      Participants watching television no more than 7 h/week presented a 19 and 21 %
      lower likelihood for hypertension (HT) and elevated total cholesterol (ETC) than
      those with television time >7 h/week. Individuals who had less television time
      and a healthy dietary pattern had a lower OR for the presence of AO (OR 0.48; 95
      % CI 0.36, 0.65), HT (OR 0.71; 95 % CI 0.66, 0.77), ETC (OR 0.72; 95 % CI 0.57,
      0.91) and elevated TAG (OR 0.76; 95 % CI 0.61, 0.95), compared with those who
      followed other dietary patterns and television time >7 h/week. In conclusion,
      both healthy traditional pattern and less television time are jointly associated
      with reduced levels of CVD risk factors. It has important public health
      implications regarding the precision prevention of CVD at population level.

PMID- 29224575
TI  - A systematic review of patient-reported outcome measures in paediatric
      otolaryngology.
AB  - BACKGROUND: Recently, there has been increased emphasis on the development and
      application of patient-reported outcome measures. This drive to assess the impact
      of illness or interventions, from the patient's perspective, has resulted in a
      greater number of available questionnaires. The importance of selecting an
      appropriate patient-reported outcome measure is specifically emphasised in the
      paediatric population. The literature on patient-reported outcome measures used
      in paediatric otolaryngology was reviewed. METHODS: A comprehensive literature
      search was conducted using the databases Medline, Embase, Cumulative Index to
      Nursing and Allied Health Literature, and PsycInfo, using the terms: 'health
      assessment questionnaire', 'structured questionnaire', 'questionnaire', 'patient
      reported outcome measures', 'PROM', 'quality of life' or 'survey', and 'children'
      or 'otolaryngology'. The search was limited to English-language articles
      published between 1996 and 2016. RESULTS: The search yielded 656 articles, of
      which 63 were considered relevant. This included general paediatric patient
      reported outcome measures applied to otolaryngology, and paediatric
      otolaryngology disease-specific patient-reported outcome measures. CONCLUSION: A
      large collection of patient-reported outcome measures are described in the
      paediatric otolaryngology literature. Greater standardisation of the patient
      reported outcome measures used in paediatric otolaryngology would assist in
      pooling of data and increase the validation of tools used.

PMID- 29224576
TI  - Using structural equation modelling to assess factors influencing children's
      growth and nutrition in rural China.
AB  - OBJECTIVE: Children's poor growth and nutrition status has serious consequences
      and therefore it is important to understand its contributing factors. DESIGN: A
      community-based interventional study focusing on child feeding was conducted in a
      rural community in China. Data from the intervention group at baseline (1-4
      months of age) and follow-up visits (12 and 18 months of age) were used in the
      present study (n 236). A structural equation model was generated to explore the
      effects of family wealth, household food safety, dietary intake, diseases and
      other factors on the growth and nutrition of young children. RESULTS: Mother's
      knowledge and behaviours on household food safety had positive effects on
      children's weight-for-age Z-score (WAZ; beta direct=0.03 and 0.15, respectively,
      at 12 months of age; beta direct=0.02 and 0.08, respectively, at 18 months;
      P<0.05) and weight-for-length Z-score (WLZ; beta direct=0.04 and 0.21,
      respectively, at 12 months of age; beta direct=0.01 and 0.06, respectively, at 18
      months; P<0.05). While mothers' feeding behaviours and children's dietary intake
      at 12 months of age were positively associated with WAZ and/or WLZ at current and
      later ages, children's diseases were negatively associated with WAZ and WLZ cross
      sectionally. CONCLUSIONS: Caregiver's knowledge and feeding behaviours, and
      children's dietary intake and diseases, are factors influencing the WAZ and WLZ
      of children. Promoting feeding and health knowledge and behaviours at early
      stages of childhood can improve children's physical growth at later ages.

PMID- 29224577
TI  - Long-term implications of feed energy source in different genetic types of
      reproductive rabbit females. II. Immunologic status.
AB  - Genetic selection and nutrition management have played a central role in the
      development of commercial rabbitry industry over the last few decades, being able
      to affect productive and immunological traits of the animals. However, the
      implication of different energy sources in animals from diverse genetic lines
      achieving such evolutionary success remains still unknown. Therefore, in this
      work, 203 female rabbits housed and bred in the same conditions were used from
      their first artificial insemination until their fifth weaning. The animals
      belonged to three different genetic types diverging greatly on breeding goals (H
      line, hyper-prolific (n=66); LP line, robust (n=67) and R line, selected for
      growth rate (n=67), and were assigned to two experimental diets, promoting major
      differences in energy source (cereal starch or animal fat)). The aims of this
      work were to: (1) characterize and describe blood leucocyte populations of three
      lines of rabbit does in different physiological stages during their reproductive
      period: first artificial insemination, first weaning, second parturition and
      fifth weaning; and (2) study the possible influence of two different experimental
      diets on the leucocyte populations in peripheral blood. Flow cytometry analyses
      were performed on blood samples taken from females at each different sampling
      stade. Lymphocyte populations at both weanings were characterized by
      significantly lower counts of total, CD5+ and CD8+ lymphocytes (-19.8, -21.7 and 
      44.6%; P<0.05), and higher counts of monocytes and granulocytes (+49.2 and
      +26.2%; P<0.05) than in the other stages. Females had higher blood counts of
      lymphocytes B, CD8+ and CD25+ and lower counts of CD4+ at first than at fifth
      weaning (+55.6, +85.8, +57.5, -14.5%; P<0.05). G/L ratio was higher at both
      weanings (P<0.05), and CD4+/CD8+ ratio increased progressively from the 1AI to
      the 5 W (P<0.001). Regarding the effect of genetic type in blood leucocyte
      counts, LP animals presented the highest counts for total, B, CD5+ and CD8+
      lymphocytes (+16.7, +31.8, +24.5 and +38.7; P<0.05), but R rabbits showed the
      highest counts for monocytes and granulocytes (+25.3 and +27.6; P<0.05). The type
      of diet given during the reproductive life did not affect the leucocyte
      population counts. These results indicate that there are detectable variations in
      the leucocyte profile depending on the reproductive stage of the animal
      (parturition, weaning or none of them). Moreover, foundation for reproductive
      longevity criteria allows animals to be more capable of adapting to the
      challenges of the reproductive cycle from an immunological viewpoint.

PMID- 29224578
TI  - Isolating the cow-specific part of residual energy intake in lactating dairy cows
      using random regressions.
AB  - The ability to properly assess and accurately phenotype true differences in feed
      efficiency among dairy cows is key to the development of breeding programs for
      improving feed efficiency. The variability among individuals in feed efficiency
      is commonly characterised by the residual intake approach. Residual feed intake
      is represented by the residuals of a linear regression of intake on the
      corresponding quantities of the biological functions that consume (or release)
      energy. However, the residuals include both, model fitting and measurement errors
      as well as any variability in cow efficiency. The objective of this study was to
      isolate the individual animal variability in feed efficiency from the residual
      component. Two separate models were fitted, in one the standard residual energy
      intake (REI) was calculated as the residual of a multiple linear regression of
      lactation average net energy intake (NEI) on lactation average milk energy
      output, average metabolic BW, as well as lactation loss and gain of body
      condition score. In the other, a linear mixed model was used to simultaneously
      fit fixed linear regressions and random cow levels on the biological traits and
      intercept using fortnight repeated measures for the variables. This method split
      the predicted NEI in two parts: one quantifying the population mean intercept and
      coefficients, and one quantifying cow-specific deviations in the intercept and
      coefficients. The cow-specific part of predicted NEI was assumed to isolate true
      differences in feed efficiency among cows. NEI and associated energy expenditure
      phenotypes were available for the first 17 fortnights of lactation from 119
      Holstein cows; all fed a constant energy-rich diet. Mixed models fitting cow
      specific intercept and coefficients to different combinations of the
      aforementioned energy expenditure traits, calculated on a fortnightly basis, were
      compared. The variance of REI estimated with the lactation average model
      represented only 8% of the variance of measured NEI. Among all compared mixed
      models, the variance of the cow-specific part of predicted NEI represented
      between 53% and 59% of the variance of REI estimated from the lactation average
      model or between 4% and 5% of the variance of measured NEI. The remaining 41% to
      47% of the variance of REI estimated with the lactation average model may
      therefore reflect model fitting errors or measurement errors. In conclusion, the
      use of a mixed model framework with cow-specific random regressions seems to be a
      promising method to isolate the cow-specific component of REI in dairy cows.

PMID- 29224579
TI  - Wilder Penfield, Sir Arthur Currie, and the Montreal Neurological Institute.
AB  - Wilder Penfield and the Montreal Neurological Institute (MNI) are inextricably
      linked. It was Penfield's unique idea to create a building with an academic
      atmosphere wherein basic neuroscience and clinical care of neurological patients
      would benefit from interaction and mutual support. It is clear that without
      Penfield that there would be no MNI; however, the role of another Canadian icon,
      Sir Arthur Currie, in the development of the MNI has heretofore been barely
      mentioned. The thesis of this paper is that Currie had a critical role in the
      gestation of the MNI that has generally been ignored.

PMID- 29224580
TI  - The neural correlates of Childhood Trauma Questionnaire scores in adults: A meta
      analysis and review of functional magnetic resonance imaging studies.
AB  - Childhood maltreatment, including abuse and neglect, may have sustained effects
      on the integrity and functioning of the brain, alter neurophysiological
      responsivity later in life, and predispose individuals toward psychiatric
      conditions involving socioaffective disturbances. This meta-analysis aims to
      quantify associations between self-reported childhood maltreatment and brain
      function in response to socioaffective cues in adults. Seventeen functional
      magnetic resonance imaging studies reporting on data from 848 individuals
      examined with the Childhood Trauma Questionnaire were included in a meta-analysis
      of whole-brain findings, or a review of region of interest findings. The spatial
      consistency of peak activations associated with maltreatment exposure was tested
      using activation likelihood estimation, using a threshold of p < .05 corrected
      for multiple comparisons. Adults exposed to childhood maltreatment showed
      significantly increased activation in the left superior frontal gyrus and left
      middle temporal gyrus, and decreased activation in the left superior parietal
      lobule and the left hippocampus. Although hyperresponsivity to socioaffective
      cues in the amygdala and ventral anterior cingulate cortex in correlation with
      maltreatment severity is a replicated finding in region of interest studies, null
      results are reported as well. The findings suggest that childhood maltreatment
      has sustained effects on brain function into adulthood, and highlight potential
      mechanisms for conveying vulnerability to development of psychopathology.

PMID- 29224581
TI  - Executive function and other cognitive deficits are distal risk factors of
      generalized anxiety disorder 9 years later.
AB  - OBJECTIVE: The cognitive model (Hirsch & Mathews, 2012) and attentional control
      theory (Eysenck & Derakshan, 2011) postulate that compromised executive function
      (EF) and other cognitive constructs are negatively linked to increased excessive
      and uncontrollable worry, the core symptom of generalized anxiety disorder (GAD).
      However, the prospective link between neuropsychological constructs and GAD are
      not well understood. METHODS: A nationally representative sample of 2605
      community-dwelling adults whose average age was 55.20 (s.d. = 11.41, range 33-84;
      56.31% females) participated at baseline and 9-year follow-up. Baseline
      neuropsychological function and symptoms were measured using the Brief Test of
      Adult Cognition by Telephone and Composite International Diagnostic Interview -
      Short Form. Multivariate Poisson and negative binomial regression analyses were
      conducted with 11 baseline covariates entered simultaneously: age, gender, years
      of formal education, perceived control, hypertension/diabetes, body mass index,
      exercise status, as well as GAD severity, panic disorder severity, and depression
      severity. Those with baseline GAD were also removed. RESULTS: Lower Time 1
      composite global cognition z-score independently predicted higher Time 2 GAD
      severity and diagnosis [odds ratio (OR) 0.60, 95% confidence interval (CI) 0.40
      0.89, p = 0.01]. Poor inhibition, set-shifting, working memory (WM) updating,
      inductive reasoning, and global cognition sequentially forecasted heightened GAD.
      However, processing speed, verbal WM, verbal fluency, and episodic memory did not
      predict future GAD. CONCLUSION: Global cognition, inductive reasoning,
      inhibition, set-shifting, and WM updating EF impairments may be distal risk
      factors for elevated GAD nearly a decade later.

PMID- 29224582
TI  - A Simple Preparation Method for Full-Range Electron Tomography of Nanoparticles
      and Fine Powders.
AB  - Electron tomography has become a valuable and widely used tool for studying the
      three-dimensional nanostructure of materials and biological specimens. However,
      the incomplete tilt range provided by conventional sample holders limits the
      fidelity and quantitative interpretability of tomographic images by leaving a
      "missing wedge" of unknown information in Fourier space. Imaging over a complete
      range of angles eliminates missing wedge artifacts and dramatically improves
      tomogram quality. Full-range tomography is usually accomplished using needle
      shaped samples milled from bulk material with focused ion beams, but versatile
      specimen preparation methods for nanoparticles and other fine powders are
      lacking. In this work, we present a new preparation technique in which powder
      specimens are supported on carbon nanofibers that extend beyond the end of a
      tungsten needle. Using this approach, we produced tomograms of platinum fuel cell
      catalysts and gold-decorated strontium titanate photocatalyst specimens. Without
      the missing wedge, these tomograms are free from elongation artifacts, supporting
      straightforward automatic segmentation and quantitative analysis of key materials
      properties such as void size and connectivity, and surface area and curvature.
      This approach may be generalized to other samples that can be dispersed in
      liquids, such as biological structures, creating new opportunities for high
      quality electron tomography across disciplines.

PMID- 29224583
TI  - Nutrients for neurocognition in health and disease: measures, methodologies and
      mechanisms.
AB  - Effective pharmaceutical treatments for age-related cognitive decline have proved
      elusive. There is, however, compelling evidence that nutritional status and
      supplementation could play crucial roles in modifying the expression of cognitive
      change through the lifespan. Subjective memory impairment and mild cognitive
      impairment can be harbingers of dementia but this is by no means inevitable.
      Neurocognitive change is influenced by a variety of processes, many of which are
      involved in other aspects of systemic health, including cardiovascular function.
      Importantly, many of these processes are governed by mechanisms which may be
      modified by specific classes of bioactive nutrients. There is increasing,
      converging evidence from controlled trials that nutritional interventions can
      improve mood and cognitive function in both clinical and healthy populations.
      Specific examples include selected botanical extracts such as the flavonoids.
      Some nutritional supplements (e.g. broad-spectrum micronutrient supplementation)
      appear to support improved cognitive function, possibly through redressing
      insufficient nutrient status (i.e. suboptimal but above the threshold for frank
      deficiency). Recent mechanistic research has unveiled physiologically plausible,
      modifiable, cognition-relevant targets for nutrition and nutraceuticals. These
      include processes involved in both systemic and central vascular function,
      inflammation, metabolism, central activation, improved neural efficiency and
      angiogenesis. The advent and development of human neuroimaging methodology have
      greatly aided our understanding of the core central mechanisms of cognitive
      change. Different imaging modalities can provide insights into modifiable central
      mechanisms which may be targeted by bioactive nutrients. The latter may
      contribute to slowing age-related decline through supporting neurocognitive
      scaffolding mechanisms.

PMID- 29224584
TI  - Long-term implications of feed energy source in different genetic types of
      reproductive rabbit females: III. Fitness and productivity.
AB  - The specialization process associated with genetic selection could be associated
      with functional disorders, affecting the reproductive success of females
      (fitness). We hypothesized that by modulating energy acquisition and allocation
      of females we could balance productivity and reproductive success. To test this
      hypothesis, we used 203 rabbit females belonging to three genetic types: H (n=66)
      maternal line specialized in prolificacy, LP (n=67) generalist maternal line, R
      (n=70) paternal line specialized in growth rate. We fed each genetic type with
      two diets specifically designed to promote milk yield (AF) or body reserves
      recovery (CS). We controlled females between their first and fifth reproductive
      cycles, recording traits related with productivity and fitness of females. H
      females fed CS had on average 11.2+/-0.43 kits with an individual weight of 54+/
      1.2 g at birth and 525+/-11 g at weaning. Their conception rate when multiparous
      was 44% and their survival rate at the end of the experiment 30%. When they were
      fed AF, the individual weight of kits was 3.8 g heavier (P<0.05) at birth and 38
      g heavier at weaning (P<0.05), the conception rate when multiparous increased 23
      percentage points (P<0.05) and the survival rate at the end of the experiment 25
      percentage points (P<0.05). LP females fed CS had on average 10.8+/-0.43 kits
      with an individual weight of 52+/-1.2 g at birth and 578+/-11 g at weaning. Their
      conception rate when multiparous was 79% and their survival rate at the end of
      the experiment 75%. When they were fed AF, it only increased individual weight of
      kits at weaning (+39 g; P<0.05). R females fed CS had on average 8.4+/-0.43 kits
      with an individual weight of 60+/-1.2 g at birth and 568+/-11 g at weaning. Their
      conception rate when multiparous was 60% and their survival rate at the end of
      the experiment 37%. When they were fed AF, they presented 1.4 kits less at birth
      (P<0.05) but heavier at birth (+4.9 g; P<0.05) and at weaning (+37 g; P<0.05).
      Therefore, we observed that genetic types prioritized different fitness
      components and that diets could affected them. In this sense, seems that more
      specialized genetic types, were more sensitive to diets than the more generalist
      type.

PMID- 29224585
TI  - Long-term implications of feed energy source in different genetic types of
      reproductive rabbit females: I. Resource acquisition and allocation.
AB  - To achieve functional but also productive females, we hypothesised that it is
      possible to modulate acquisition and allocation of animals from different genetic
      types by varying the main energy source of the diet. To test this hypothesis, we
      used 203 rabbit females belonging to three genetic types: H (n=66), a maternal
      line characterised by hyper-prolificacy; LP (n=67), a maternal line characterised
      by functional hyper-longevity; R (n=79), a paternal line characterised by growth
      rate. Females were fed with two isoenergetic and isoprotein diets differing in
      energy source: animal fat (AF) enhancing milk yield; cereal starch (CS) promoting
      body reserves recovery. Feed intake, weight, perirenal fat thickness (PFT), milk
      yield and blood traits were controlled during five consecutive reproductive
      cycles (RCs). Females fed with CS presented higher PFT (+0.2 mm, P0.05),
      particularly for those fed with AF. Moreover, LP females fed with AF
      progressively increased PFT across the RC, whereas those fed with CS increased
      PFT during early lactation (+7.3%; P<0.05), but partially mobilised it during
      late lactation (-2.8%; P<0.05). Independently of the diet offered, LP females
      reached weaning with similar PFT. H females fed with either of the two diets
      followed a similar trajectory throughout the RC. For milk yield, the effect of
      energy source was almost constant during the whole experiment, except for the
      first RC of females from the maternal lines (H and LP). These females yielded
      +34.1% (P<0.05) when fed with CS during this period. Results from this work
      indicate that the resource acquisition capacity and allocation pattern of rabbit
      females is different for each genetic type. Moreover, it seems that by varying
      the main energy source of the diet it is possible to modulate acquisition and
      allocation of resources of the different genetic types. However, the response of
      each one depends on its priorities over time.

PMID- 29224586
TI  - A scoping review of the evidence for efficacy of acupuncture in companion
      animals.
AB  - Acupuncture has become increasingly popular in veterinary medicine. Within the
      scientific literature there is debate regarding its efficacy. Due to the complex
      nature of acupuncture, a scoping review was undertaken to identify and categorize
      the evidence related to acupuncture in companion animals (dogs, cats, and
      horses). Our search identified 843 relevant citations. Narrative reviews
      represented the largest proportion of studies (43%). We identified 179
      experimental studies and 175 case reports/case series that examined the efficacy
      of acupuncture. Dogs were the most common subjects in the experimental trials.
      The most common indication for use was musculoskeletal conditions, and the most
      commonly evaluated outcome categories among experimental trials were pain and
      cardiovascular parameters. The limited number of controlled trials and the
      breadth of indications for use, outcome categories, and types of acupuncture
      evaluated present challenges for future systematic reviews or meta-analyses.
      There is a need for high-quality randomized controlled trials addressing the most
      common clinical uses of acupuncture, and using consistent and clinically relevant
      outcomes, to inform conclusions regarding the efficacy of acupuncture in
      companion animals.

PMID- 29224587
TI  - The prevalence of Behcet's disease in the north of Jordan: a hospital-based
      epidemiological survey.
AB  - OBJECTIVES: To estimate the prevalence of Behcet's disease (BD) in Jordan, with
      the additional aim of comparing this prevalence among hospital workers in other
      geographical areas. METHODS: In the first stage of our survey, 2,569 employees
      from 6 hospitals in north Jordan were interviewed using a screening questionnaire
      to identify individuals with recurrent oral ulcers (ROU), a previous diagnosis of
      BD (PDBD) and/or any major symptom related to BD. In the second stage, all
      individuals with ROU or PDBD identified at stage 1, were examined by 2
      rheumatologists for the presence/confirmation of BD according to the
      International Study Group (ISG) criteria. Pathergy test was performed according
      to recommendations. RESULTS: ROU were present in 210 (8.2%) individuals. BD was
      confirmed in 10 employees with PDBD. Seven more BD patients were found. Mean age
      of 17 BD patients was 38.6+/-10.7 (range 26-65 y). M: F was 2.4:1. Pathergy test
      was positive in 8/17. A family history of ROU or BD was noted in 9 (52%) and 3
      (25.0%), respectively, compared to 227 (8.9%) and 62 (2.6%) in the whole group,
      excluding the BD patients (p<0.001 and 0.008, respectively). The prevalence rate
      of BD in the north of Jordan was estimated as 66:10.000 (95% CI 34.8 to
      97.5:10000). CONCLUSIONS: The results of this first ever survey indicated that
      the prevalence of BD in the north of Jordan is among the highest in the world.
      This prevalence can now be compared to hospital workers in other geographical
      areas.

PMID- 29224588
TI  - Alteration of the microRNA expression profile in familial Mediterranean fever
      patients.
AB  - OBJECTIVES: Phenotypic heterogeneity in familial Mediterranean fever (FMF)
      disease indicated that FMF is not a simple monogenic disease. Therefore it has
      been suggested that epigenetic factors can be one of the reason for the
      variations. We undertook this study to test potential involvement of miRNAs in
      the pathogenesis of FMF. METHODS: miRNA array was performed on whole blood RNA
      samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers
      who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-).
      The raw data was analysed by Multi Experiment Viewer (MeV) and candidate miRNAs
      were determined according to fold change (more than 2.0 or less than -2.0). The
      validation of differentially expressed miRNAs was done by qRT-PCR. Then we
      performed pathway analyses with using bioinformatics tools. RESULTS: 14 miRNAs
      were found to be significant among groups through the analysis with MeV. miR-20a
      5p, miR-197-3p, let-7d-3p and miR-574-3p were found to be associated with
      inflammatory pathway related genes according to DAVID analysis. MiR-20a-5p (FDR:
      0,00, FCH: 5.55) was significantly up regulated whereas miR-197-3p (FDR: 0,00,
      FCH: -2.27) was down regulated in homozygotes patients. Both let-7d-3p (FDR:
      0.00, FCH: 28.75) and miR-574-3p (FDR: 0.00, FCH: 3.95) were up regulated in
      heterozygote patients group. CONCLUSIONS: We showed that there are several
      differentially expressed miRNAs both in homozygote and heterozygote FMF patients
      compared to controls and healthy carriers. Thus we suggest that these miRNAs,
      related with inflammatory pathways may be responsible for the expression of the
      disease in FMF.

PMID- 29224589
TI  - A wake-up call for physical activity promotion in Australia: results from a
      survey of Australian nursing and allied health professionals.
AB  - Objective Nursing and allied health professionals (AHPs) are in an ideal position
      to promote physical activity (PA) as part of their health care provision. The aim
      of this study was to investigate current promotion and knowledge of PA among
      people in these disciplines.Methods A cross-sectional online survey of practicing
      Australian physiotherapists, nurses, exercise physiologists, occupational
      therapists, dietitians and pharmacists was conducted in 2016.Results A total of
      433 nurses and AHPs completed the survey. All disciplines agreed that providing
      PA advice was part of their role, although nurses were less likely to agree. All
      disciplines felt they had the skills to promote PA but nurses were more likely to
      report a lack of time as a barrier. Physiotherapists and exercise physiologists
      were more confident giving PA advice to patients. Most health professionals (68%)
      were aware of the PA guidelines, although only 16% were accurately able to
      describe all relevant components. In logistic regression modelling, women and
      those working in public hospitals were less likely to encourage PA. Awareness of
      the PA guidelines doubled the odds of encouraging PA in patients (odds ratio
      2.01, 95% confidence interval 1.18-3.43).Conclusions Australian nurses and AHPs
      perceive that PA promotion is part of their role, however few have specific
      knowledge of the PA guidelines. To increase PA promotion by nurses and AHPs
      awareness of the PA guidelines appears to be essential.What is known about the
      topic? Nurses and AHPs are in an ideal position to promote PA, although there is
      limited evidence of their PA promotion and knowledge.What does the paper add?
      Australian nurses and AHPs are confident and think it is feasible to promote PA
      to patients in several healthcare settings but many lack sufficient PA knowledge,
      limiting their PA promotion.What are the implications for practitioners?
      Increasing PA knowledge of nurses and AHPs could generate increased levels of PA
      in the Australian population and improve national health and wellbeing.

PMID- 29224596
TI  - Improving Health Services: Background, Method and Applications.

PMID- 29224590
TI  - Comparative emergency department resource utilisation across age groups.
AB  - Objectives The aim of the present study was to assess comparative emergency
      department (ED) resource utilisation across age groups.Methods A retrospective
      analysis of data collected in the National Non-admitted Patient Emergency
      Department Care Database was undertaken to assess comparative ED resource
      utilisation across six age groups (0-14, 15-35, 36-64, 65-74, 75-84 and >=85
      years) with previously used surrogate markers of ED resource utilisation.Results
      Older people had significantly higher resource utilisation for their individual
      ED episodes of care than younger people, with the effect increasing with
      advancing age.Conclusion With ED care of older people demonstrated to be more
      resource intensive than care for younger people, the projected increase in older
      person presentations anticipated with population aging will have a magnified
      effect on ED services. These predicted changes in demand for ED care will only be
      able to be optimally managed if Australian health policy, ED funding instruments
      and ED models of care are adjusted to take into account the specific care and
      resource needs of older people.What is known about the topic? Current Australian
      ED funding models do not adjust for patient age. Several regional studies have
      suggested higher resource utilisation of ED patients aged >=65 years. Anticipated
      rapid population aging mandates that contribution of age to ED visit resource
      utilisation be further explored.What does this paper add? The present study of
      national Australian ED presentations compared ED resource utilisation across age
      groups using surrogate markers of ED cost. Older people were found to have
      significantly higher resource utilisation in the ED, with the effect increasing
      further with advancing age.What are the implications for practitioners? The
      higher resource utilisation of older people in the ED warrants a review of
      current ED funding models to ensure that they will continue to meet the needs of
      an aging population.

PMID- 29224597
TI  - Corrigendum to: Public sector residential aged care: identifying novel
      associations between quality indicators and other demographic and health-related
      factors.
AB  - To explore associations among quality indicators (QI; e.g. pressure ulcers, falls
      and/or fractures, physical restraint, use of multiple medications, unplanned
      weight loss) of the Victorian Public Sector Residential Aged Care Services
      (VPSRACS) with other demographic and health-related factors. Data for 380
      residents over a 3-month period were extracted retrospectively from client
      databases at four VPSRAC facilities. Four significant logistic regression models
      were developed. The strongest models related to falls and polypharmacy.
      Significant associations for these models included the following: (1) residents
      with a higher body mass index were 6% less likely (95% confidence interval (CI)
      1%-11%) to fall, whereas high levels of cognitive impairment increased the risk
      of falling by 8% (95% CI 2%-14%); (2) being ambulant with a gait aid more than
      doubled the risk of falling compared with non-ambulant residents (95% CI 19%
      546%); and (3) higher cognitive impairment was associated with a 6% (95% CI 1%
      11%) reduction in the likelihood of polypharmacy. Identification of significant
      relationships between the VPSRACS QI and other demographic and health-related
      factors is a preliminary step towards a more in-depth understanding of the
      factors that influence the QI and predict adverse events. Currently, the VPSRACS
      report on five QI. Previous research has shown associations between several of
      these indicators, but not all. This paper examines associations between the five
      VPSRAC QI as well as other key demographic and health-related factors. Novel
      findings from regression analyses included an increased risk of falls associated
      with recommended body mass index and using gait aids, but no association between
      pressure ulcers and the Norton score. Regression models for other QI were limited
      by the small occurrences of the QI. However, significant associations were
      identified indicating that residents using a gait aid had a lower level of
      unplanned weight loss and residents with polypharmacy had higher unplanned weight
      loss. This paper reinforces the value of collecting VPSRAC QI data to enable
      facilities to consider how these variables could impact on care quality and to
      proactively plan to reduce the risk of adverse events. Although QI data can be
      used to benchmark with other settings, this paper shows how QI data can be used
      to inform practice within a facility and help identify patient-related factors
      that may warrant further investigation.

PMID- 29224600
TI  - Evaluation of an integrated housing and recovery model for people with severe and
      persistent mental illnesses: the Doorway program.
AB  - Objective The Doorway program is a 3-year pilot integrated housing and recovery
      support program aimed at people with a severe and persistent mental illness who
      are 'at risk' or actually homeless. Participants source and choose properties
      through the open rental market, with appropriate rental subsidy and brokerage
      support. This arrangement is highly innovative, differing from widely favoured
      arrangements internationally involving congregate and scattered-site housing
      owned or managed by the support program. The aim of the present study was to
      determine the effects of the Doorway program on participants' health, housing,
      service utilisation and costs. Methods A pre-post study design was used with
      outcome measures consisting of a number of question inventories and their costs
      (where relevant). The principal inventories were the Behaviour and Symptom
      Identification Scale 32 (BASIS-32), a consumer-oriented, self-report measure of
      behavioural symptoms and distress, the Health of the Nation Outcome Scale
      (HoNOS), an interviewer-administered measurement tool designed to assess general
      health and social functioning of mentally ill people and the Outcomes Star
      (Homelessness) system which measures various aspects of the homelessness
      experience. Baseline measurements were performed routinely by staff at entry to
      the program and then at 6-monthly intervals across the evaluation period. Results
      For 55 of 59 participants, total mean BASIS-32 scores (including as well three of
      five subscale scores) improved significantly and with moderate effect size. Four
      of the 10 domain scores on the Outcome Star (Homelessness) inventory also
      improved significantly, with effect sizes ranging from small-medium (three
      domains) to large (one domain). Mean usage of bed-based mental health clinical
      services and general hospital admissions both significantly decreased (with
      overall net savings of A$3096 per participant per annum). Overall cost savings
      (including housing) to government ranged from A$1149 to A$19837 depending on the
      housing type comparator. Conclusion The Doorway program secured housing for this
      vulnerable group with additional benefits in client outcomes, including reduced
      use and cost of health services. These findings, if confirmed in larger studies,
      should have widespread applicability internationally. What is known about the
      topic? Beneficial effects of housing and recovery programs (Housing First) on
      people with severe and persistent mental illness and who are 'at risk', or
      actually homeless, are being demonstrated in Northern America. These effects
      include housing security, well being, health service utilisation and cost effects
      on government. However, these beneficial effects can only be regarded as settled
      for housing security. The highly innovative Doorway care model in which
      participants source and choose properties through the open rental market, with
      appropriate rental subsidy and brokerage support, has not been investigated
      previously. What does this paper add? This paper adds new data on the Doorway
      care models, it's effects and costs, particularly with regard to participant
      behavioural distress and social functioning. What are the implications for
      practitioners? The beneficial effects of this innovative model, if confirmed in
      larger studies, should have widespread applicability internationally.

PMID- 29224609
TI  - Lead...Leader...Leadership.

PMID- 29224610
TI  - Perceptions of interactions between staff members calling, and those responding
      to, rapid response team activations for patient deterioration.
AB  - Objectives The aim of the present study was to investigate experiences of staff
      interactions and non-technical skills (NTS) at rapid response team (RRT) calls,
      and their association with repeat RRT calls. Methods Mixed-methods surveys were
      conducted of RRT members and staff who activate the RRT (RRT users) for their
      perceptions and attitudes regarding the use of NTS during RRT calls. Responses
      within the survey were recorded as Likert items, ranked data and free comments.
      The latter were coded into nodes relating to one of four NTS domains: leadership,
      communication, cooperation and planning. Results Two hundred and ninety-seven
      (32%) RRT users and 79 (73.8%) RRT members provided responses. Of the RRT user
      respondents, 76.5% had activated the RRT at some point. Deficits in NTS at RRT
      calls were revealed, with 36.9% of users not feeling involved during RRT calls
      and 24.7% of members perceiving that users were disinterested. Unresolved user
      clinical concerns, or persistence of RRT calling criteria, were reasons cited by
      37.6% and 23%, respectively, of RRT users for reactivating an RRT to the same
      patient. Despite recollections of conflict at previous RRT calls, 92% of users
      would still reactivate the RRT. The most common theme in the free comments
      related to deficiencies in cooperation (52.9%), communication (28.6%) and
      leadership (14.3%). Conclusions This survey of RRT users and members revealed
      problems with RRT users' and members' interactions at the time of an RRT call.
      Both users and members considered NTS to be important, but lacking. These
      findings support NTS training for RRT members and users. What is known about the
      topic? Previous surveying has related experiences of criticism and conflict
      between clinical staff at RRT activations. This leads to reluctance to call the
      RRT when indicated, with risks to patient safety, especially if subsequent RRT
      activation is necessary. Training in NTS has improved clinician interactions in
      simulated emergencies, but the exact role of NTS during RRT calls has not yet
      been established. What does this paper add? The present survey examined
      experienced clinicians' perceptions of the use of NTS at RRT calls and the effect
      on subsequent calling. A key finding was a disparity between perceptions of how
      RRT members interact with those activating the RRT (RRT users) and their
      performance of NTS. This was reflected with unresolved RRT user clinical concern
      at the time of a call. In turn, this affected RRT users' attitudes and intentions
      to reactivate the RRT. Formal handover was considered desirable by both RRT users
      and members. What are the implications for practitioners? The interface between
      the RRT and those who call the RRT is crucial. This survey shows that RRT users
      desire to be included in the management of the deteriorating patient and have
      their concerns addressed before completion of RRT attendance. Failure to do so
      results in repeat activations to the same patient, with the potential for adverse
      patient outcomes. Training to include NTS, especially around handover, for RRT
      members may address this issue and should be explored further.

PMID- 29224613
TI  - An Elderly Physician's Plea.

PMID- 29224614
TI  - The Reply.

PMID- 29224615
TI  - Does Digital Rectal Examination Reduce Subsequent Hospitalizations and
      Endoscopies or Vice Versa?

PMID- 29224616
TI  - Does Digital Rectal Examination Predict Hospital Admission and Resource
      Utilization Rate in Patients with Acute Gastrointestinal Bleeding with Bright Red
      Blood Per Rectum?

PMID- 29224617
TI  - Will Physicians Stop Performing Physical Examinations?

PMID- 29224619
TI  - Physicians Should Always Perform a Physical Examination.

PMID- 29224618
TI  - The Reply.

PMID- 29224620
TI  - Exploring Trichoderma and Aspergillus secretomes: Proteomics approaches for the
      identification of enzymes of biotechnological interest.
AB  - Filamentous fungal secretomes comprise highly dynamic sets of proteins, including
      multiple carbohydrate active enzymes (CAZymes) which are able to hydrolyze plant
      biomass polysaccharides into products of biotechnological interest such as
      fermentable sugars. In recent years, proteomics has been used to identify and
      quantify enzymatic and non-enzymatic polypeptides present in secretomes of
      several fungi species. The resulting data have widened the scientific
      understanding of the way filamentous fungi perform biomass degradation and
      offered novel perspectives for biotechnological applications. The present review
      discusses proteomics approaches that have been applied to the study of fungal
      secretomes, focusing on two of the most studied filamentous fungi genera:
      Trichoderma and Aspergillus.

PMID- 29224621
TI  - Functional expression enhancement of Bacillus pumilus CotA-laccase mutant WLF
      through site-directed mutagenesis.
AB  - Bacterial laccases are potential enzymes for biotechnological applications, such
      as detoxification of industrial effluents, decolorization of textile, and
      dimerization of phenolic acids, due to their remarkable advantages, including
      broad substrate spectrum, high thermostability, wide pH scope, and tolerance to
      alkaline environments. L386W/G417L/G57F (abbreviated as WLF), a good mutant of
      CotA-laccase from Bacillus pumilus W3, has been constructed and reported by our
      laboratory with highly improved catalytic efficiency. However, the low-functional
      expression level of mutant WLF in Escherichia coli was a shortcoming. Three
      mutants, namely, K317N/WLF, D501G/WLF, and K317N/D501G/WLF, were constructed
      through site-directed mutagenesis to improve the functional expression of WLF in
      this study. The soluble and active expression of D501G/WLF and K317N/D501G/WLF in
      E. coli enhanced 4.48-fold and 3.63-fold level, respectively. The K317N/WLF
      failed to increase the soluble expression level, but slightly improved the
      stability of CotA-laccase. Results showed that not only the position 501 is
      significant for functional expression of B. pumilus W3 CotA, but also these
      mutants still remained its high thermostability, resistance of alkaline with
      salt, and conspicuous decolorizing efficiency. This work is the first to improve
      the soluble expression of B. pumilus CotA-laccase in E. coli by site-directed
      mutagenesis. The D501G/WLF and K317N/D501G/WLF will be suitable candidates for
      biotechnological applications.

PMID- 29224622
TI  - Increased activity of beta-glucuronidase variants produced by site-directed
      mutagenesis.
AB  - beta-glucuronidase (BGus) is an essential glycosyl hydrolase which has been
      widely used in biological and biomedical applications. In this paper, we report
      the construction and screening of nineteen Escherichia coli BGus (EBGus) mutants
      using site-directed mutagenesis. The mutants G559N, G559S and G559T showed a 3-5
      fold increase in enzyme activity in comparison to wild type EBGus. In particular,
      G559S, with the highest activity, showed 2-6 fold enhanced activity compared to
      abalone and snail BGus extracts. Moreover, the glycine to serine mutagenesis for
      the same site in Staphylococcus sp. RLH1 BGus (StBGus) exhibited significantly
      enhanced activity, which indicated the importance of the G559->S mutation on BGus
      function. Based on this structural analysis, we postulate that the mutation at
      G559 plays an important role in the stabilization of the enzyme conformation, and
      thereby facilitates the effective binding of substrate.

PMID- 29224623
TI  - Deactivation and activation of lignocellulose degrading enzymes in the presence
      of laccase.
AB  - Cellulase and hemicellulase activities in a 1:1 ratio of enzymes extracted from
      Chrysoporthe cubensis and Penicillium pinophilum were evaluated in the presence
      of known monocomponent phenolic inhibitors and also with phenol mixtures derived
      from alkali pretreated sugarcane bagasse. The cellulolytic activities from C.
      cubensis:P. pinophilum displayed a much higher tolerance to phenolic inhibitors
      than equivalent enzyme activities obtained from Trichoderma reesei and
      Aspergillus niger. Enzymes from T. reesei and A. niger were deactivated at 0.3
      and 1.5mg phenols/mg protein, respectively, as reported previously, while enzymes
      from C. cubensis:P. pinophilum resisted deactivation at 35mg phenols/mg protein.
      However, tolerance of xylanase with respect to phenols required the presence of
      laccase. Removal of laccase (enzyme) activity using sodium azide resulted in a 2x
      higher xylanase deactivation (from 40% to 80%). This paper identifies enzymes
      that are phenol tolerant, and whose adoption for lignocellulose hydrolysis could
      contribute to reductions in enzyme loading needed to hydrolyze alkali pretreated
      lignocellulosic substrates in the presence of lignin derived phenols.

PMID- 29224624
TI  - Baeyer-Villiger monooxygenases from Yarrowia lipolytica catalyze preferentially
      sulfoxidations.
AB  - Nine new putative Baeyer-Villiger monooxygenase encoding genes were identified in
      the eukaryote Yarrowia lipolytica and eight were subsequently cloned and
      expressed. These enzymes, Yarrowia monooxygenases A-H (YMOA-H), were used in
      biocatalysis reactions with ketones, sulfides and sulfoxides as substrates. YMOB
      converts ketones and sulfides, albeit with low activities. However, YMOA did not
      convert any of the tested ketone substrates, but showed activity towards sulfides
      and sulfoxides and also showed very high stereoselectivity. This enzyme produced
      high amounts of sulfones and even converted dimethylsulfoxide (DMSO). Therefore,
      the sulfoxidation activity of YMOA was investigated in a mutational study.
      Variants with increased and reduced sulfone yields were created, indicating
      relevant amino acid positions for the control of sulfoxidation activity. This
      work expands the set of eukaryotic BVMOs and explores the Yarrowia monooxygenase
      A, which might belong to a new class of BVMOs as indicated by its unique activity
      and a phylogenetic analysis.

PMID- 29224625
TI  - Peroxidase chemically attached on polymeric micelle and its reaction with
      phenolic compounds.
AB  - Horseradish peroxidase was chemically modified with comb-shaped polymaleic
      anhydride-alt-1-tetradecene (PMA-TD) in microemulsion systems to produce surface
      active peroxidase that has capability to form micellar structures in aqueous
      solutions and can be concentrated at liquid/liquid interfaces without unfolding
      of the enzyme. For chemical modification oil-in-water (O/W) and water-in-oil
      (W/O) microemulsion systems composed of n-butyl acetate and a buffer solution
      were prepared because n-butyl acetate turned out to be less detrimental to the
      activity of peroxidase at high degree of modification compared to other organic
      solvents. The modification degree of amine groups on the surface of peroxidase by
      maleic anhydride groups on PMA-TD was reached at equilibrium after 1h reaction at
      0 degrees C, and 42% of amine groups were modified with 7-fold amount of PMA-TD
      to peroxidase (wt/wt). The activity of the PMA-TD-modified peroxidase measured
      with 2,4-dichlorophenol at pH 7.0 was increased by approximately 2-fold compared
      to native peroxidase. There was no significant shift in optimum pH after
      modification, and optimum pH measured with 2,4-dichlorophenol was observed at pH
      7.0. For all six phenolic compounds tested, there was a significant increase in
      the reaction efficiency with the PMA-TD-modified peroxidase. The remarkable
      enhancement of the reaction efficiency by the modification was presumably because
      of micellar structures of PMA-TD that could concentrate hydrophobic phenolic
      oligomers into the core of the micelles. Overall, horseradish peroxidase
      chemically attached to the surface of PMA-TD micelles was found to be
      significantly effective for the oxidative polymerization of phenolic compounds.

PMID- 29224626
TI  - Development of a bacterial propionate-biosensor for anaerobic digestion
      monitoring.
AB  - Monitoring anaerobic digestion (AD) leachate for changes in acetate and
      propionate concentrations is essential for effective AD operation. In this paper
      the development of a novel propionate cell-based biosensor is described. A
      previously designed E. coli mutant (IMD Wldgy) that could selectively determine
      acetate concentrations in synthetic leachates, based on oxygen uptake
      measurements, was used as a starting point in the development of a propionate
      biosensor. However, the propionate-grown IMD Wldgy cells exhibited extremely low
      propionate:acetate O2 consumption ratios (1:2.4). Screening for alternative
      propionate-grown E. coli strains naturally possessing a more favourable
      propionate:acetate O2 consumption ratio identified strain IMD 1, which exhibited
      a positive ratio (1.6:1). To improve the selectivity of the strain, successive
      gene knockouts were performed generating the IMD 1 hldgyep mutant. However,
      propionate-grown IMD 1hdlgyep's O2 consumption ratio was deemed too low to be
      considered as a propionate detecting bio-element. It was reasoned that the
      mechanisms by which E. coli activates acetate had to be removed. Deleting acs
      (acetyl-CoA synthesase) and ackA (acetate kinase) from IMD Wldgyep, resulted in
      an E. coli IMD Wldgyepak knockout mutant that, when grown on propionate, produced
      a mean propionate:acetate O2 consumption ratio of approx. 13:1. The resulting IMD
      Wldgyep and IMD Wldgyepak strains, which formed the acetate- and propionate
      biosensor, respectively, were capable of detecting acetate and propionate
      concentrations ranging from 0.05mM to 4.5mM within two-phase AD synthetic
      leachates.

PMID- 29224627
TI  - Metabolic engineering of Escherichia coli for acetaldehyde overproduction using
      pyruvate decarboxylase from Zymomonas mobilis.
AB  - For the sustainable production of acetaldehyde, a key raw-material for a large
      number of chemical products, microbial production is a promising alternative. We
      have engineered an Escherichia coli strain for acetaldehyde production from
      glucose by introducing the pyruvate decarboxylase (Pdc) from Zymomonas mobilis
      and NADH oxidase (Nox) from Lactococcus lactis. Acetaldehyde production was
      systematically improved by knocking out the competing metabolic pathways.
      Multiple knockout strains were created and a final acetaldehyde titre of 0.73g/L
      was achieved using a quadruple knockout strain E. coli MC4100 DeltaadhE DeltaldhA
      DeltafrdC DeltaackA-pta. In addition to acetaldehyde, about 0.37g/L acetoin was
      produced by these strains due to the additional carboligase activity exhibited by
      pyruvate decarboxylase resulting in a total carbon yield of 0.27g/g glucose.

PMID- 29224628
TI  - Co-immobilization of enoate reductase with a cofactor-recycling partner enzyme.
AB  - Herein we established co-immobilized methods for enoate reductases (ERs) and
      glucose dehydrogenase (GDH), forming a cofactor regeneration system. In cross
      linked enzyme aggregates (CLEAs), ammonium sulfate and oxidized dextran were
      selected as a precipitant and a cross-linker, respectively. In biomimetic
      immobilization (BI), ER-GDH-silica particles (ER-GDH-SPs) were rapidly formed
      through a one-step approach by using a silicic acid precursor. Under the optimal
      conditions, the ER activity recovery in ER-GDH-CLEAs and ER-GDH-SPs were 44.9+/
      1.8% and 44.5+/-2.1%, and the immobilization efficiency was 93.5+/-1.2% and
      92.4+/-1.2%, respectively. ER-GDH-CLEAs and ER-GDH-SPs exhibit excellent thermal
      and pH stability, and superior reusability. The activity of ER-GDH-SPs toward the
      substrate is also better than that of free ER and GDH in reduction of 4-(4
      Methoxyphenyl)-3-buten-2-one. This study introduces simple and inexpensive co
      immobilization strategies to construct novel and efficient ER-GDH-CLEAs and ER
      GDH-SPs with high activity and stability.

PMID- 29224629
TI  - Heterologous expression and characterization of a putative glycoside hydrolase
      family 43 arabinofuranosidase from Clostridium thermocellum B8.
AB  - An extensive list of putative cellulosomal enzymes from C. thermocellum is now
      available in the public databanks, however, most of these remain unvalidated with
      regard to their activity and expression control mechanisms. This is particularly
      true of those enzymes putatively involved in hemicellulose deconstruction. Our
      research group has been working on mapping and characterization of glycoside
      hydrolases produced by C. thermocellum B8, that are critical for lignocellulosic
      biomass deconstruction. One of the identified genes expressed during growth on
      sugar cane bagasse and straw is axb8, which encodes a putative cellulosomal
      GH43_29 alpha-arabinofuranosidase (EC 3.2.1.55) that has not previously been
      characterized at the molecular or kinetic levels. The AxB8 predicted amino acid
      sequence presented GH43 and dockerin domains, as well as a family 6 carbohydrate
      binding module (CBM6). Also, it is a close homologue of Firmicutes putatives
      alpha-arabinofuranosidases, including cellulosomal proteins. Multiple alignment
      analysis grouped AxB8 in a cluster with four uncharacterized putative GH43_29
      subfamily enzymes, all containing dockerin type I domain and CBM6 modules.
      Purified heterologously expressed AxB8 showed activity against the synthetic
      substrates pNPX (p-nytrophenyl-beta-d-xylopyranoside) and pNPA (p-nytrophenyl
      alpha-l-arabinofuranoside), as well as against the natural substrate wheat
      arabinoxylan (WAX), with maximal activity at 50 degrees C and pH between 5.0 and
      6.0. The WAX degradation profile by AxB8 is different from those typically seen
      for alpha-arabinofuranosidases, presenting mainly xylose as a hydrolysis product,
      instead of arabinose. In addition, unlike other GH43_29 enzymes already
      characterized, AxB8 did not present activity against arabinan. Kinetic parameters
      using pNPA as a substrate were Km of 23+/-3mM and kcat of 104+/-7s-1. Despite its
      activity against pNPX, we did not observe AxB8 saturation with this substrate.
      AxB8 is the first member in its clade to be characterized regarding kinetic
      parameters, and together with its closest homologues could represent a large
      group of glycoside hydrolases with particular properties within the GH43_29
      subfamily.

PMID- 29224630
TI  - TIME in the Context of Emerging Evidence Regarding Training Interventions for
      Dementia in Nursing Homes.

PMID- 29224631
TI  - Treatment outcomes of rifabutin-containing regimens for rifabutin-sensitive
      multidrug-resistant pulmonary tuberculosis.
AB  - OBJECTIVES: The aim of this study was to evaluate whether rifabutin can improve
      treatment outcomes in patients with rifabutin-sensitive MDR-TB. METHODS: A
      retrospective cohort study was performed on 76 patients with rifabutin-sensitive
      MDR-TB who were treated with or without rifabutin between 2006 and 2011. RESULTS:
      Overall, 75% (57/76) of patients achieved favorable outcomes, including cure
      (53/76, 70%) and treatment completion (4/76, 5%). In contrast, 25% (19/76) had
      unfavorable treatment outcomes, which included treatment failure (6/76, 8%),
      death (2/76, 3%), loss to follow-up (4/76. 5%), and no evaluation due to transfer
      to other institutions (7/76, 9%). Rifabutin was given to 52 (68%) of the 76
      patients with rifabutin-sensitive MDR-TB. Although favorable treatment outcomes
      were more frequent in patients who received rifabutin [81% (42/52)] than in those
      who did not receive rifabutin [63% (15/24)], this difference was not
      statistically significant (P=0.154). However, in multivariable regression
      logistic analysis, use of rifabutin was significantly associated with favorable
      treatment outcomes in patients with rifabutin-sensitive MDR-TB (adjusted odds
      ratio=9.80, 95% confidence interval=1.65-58.37, P=0.012). CONCLUSIONS: These
      results suggest that the use of rifabutin can improve treatment outcomes in
      patients with rifabutin-sensitive MDR-TB.

PMID- 29224632
TI  - Pharmacy Practice and Diabetes Care.

PMID- 29224633
TI  - Over-the-Counter Medicines and Diabetes Care.
AB  - OBJECTIVES: People with diabetes turn to over-the-counter (OTC) medicines for
      many ailments. The focus of this brief review is the impact common OTC medicines
      might have on this group of patients. METHODS: Three types of OTC medicines were
      selected as most deserving of attention: 3 herbal agents, nonsteroidal anti
      inflammatory drugs (NSAIDs) and cough/cold products. Existing literature was used
      to determine precautions that might be in order. RESULTS: Herbal/natural agents
      with the potential to impact blood sugar have been identified in various reports.
      In discussing 3, glucosamine and cinnamon (at doses recommended on commercial
      products) should have minimal impact on diabetic management, whereas St. John's
      wort is a concern involving potential drug interactions. For colds, of about 11
      active ingredients, only decongestants (primarily oral) need be considered for
      their possible effects on blood sugar. Finally, NSAIDs (even at OTC doses) must
      be used with caution, given their cardiovascular, renal and gastrointestinal
      risks. Care guidelines do encourage patients to take ownership of their
      condition. Yet the ability to self-medicate safely is not a certainty. In spite
      of easy access and a reasonable level of safety, OTC medicines still can
      negatively impact a user. NSAIDs available without prescription continue to cause
      concern. CONCLUSIONS: Before the use of any medicine, a person must ensure it
      will be safe. A health-care provider can be asked for assistance, but that option
      may not always be employed. Package information is there to provide critical
      information in lieu of that, something the self-medicating patient will, it is
      hoped, embrace.

PMID- 29224634
TI  - Creation of a Diabetes Pharmacists Network in Canada.

PMID- 29224635
TI  - Community Pharmacists' Perspectives of a Decision Aid for Managing Type 2
      Diabetes in Ontario.
AB  - OBJECTIVES: Decision aids are tools designed to help patients make choices about
      their health care. We explored pharmacists' perceptions of an evidence-based
      diabetes decision aid developed by the Mayo Clinic, Diabetes Medication Choice
      (DMC). Using DMC as a reference, we aimed to explore pharmacists' perspectives on
      decision aids, their place in a community pharmacy setting and the implementing
      of a decision aid, such as DMC, in Ontario. METHODS: We used semistructured
      interviews with a convenience sample of community pharmacists from Ontario. We
      applied a thematic analysis to the data. RESULTS: We conducted 16 interviews with
      pharmacists, of whom 9 were certified diabetes educators, and 10 were female.
      Three themes emerged from the data: pharmacists' knowledge and awareness of
      decision aids; pharmacists' perceptions of the DMC decision aids, and
      implementation of the DMC decision aids in Ontario pharmacies. Participants
      discussed their limited experience with and training in the use of decision aids.
      Although many participants agreed that the DMC decision aids may contribute to
      patient-centred care, all agreed that significant changes were needed to be made
      to implement this tool in practice. CONCLUSIONS: Pharmacists felt that the use of
      decision aids in community pharmacies in Ontario may improve patient-centred
      care. Modifications, however, are needed to improve the applicability to their
      context and fit into their workflow. Empirical data concerning the impact of
      decision aids in community pharmacy is needed.

PMID- 29224636
TI  - Effects of Pharmacy-Based Interventions on the Control and Management of Diabetes
      in Adults: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate
      the effects of pharmacy-based interventions on clinical outcomes associated with
      diabetes-related complications as well as on nonclinical outcomes in people with
      diabetes. METHODS: We searched 4 main databases (MEDLINE, EMBASE, CINAHL and
      Cochrane Central Register of Controlled Trials) for studies that considered
      clinical and nonclinical outcomes of pharmacy-based interventions among people
      with diabetes. Clinical outcomes included patients' mean reductions of glycated
      hemoglobin (A1C) levels and body mass indexes (BMIs). Nonclinical outcomes
      included patients' healthcare utilization and quality of life. A meta-analysis
      was conducted to estimate the pooled net mean difference in clinical outcomes
      between the pharmacy-intervention and the control groups. RESULTS: Of the 44
      studies included in the systematic review, 32 studies reported results from
      randomized controlled trials measuring reductions of A1C levels in 4,132
      patients. Meta-analysis revealed that the standardized absolute mean difference
      in reduction of A1C levels from baseline to the time of the last follow up
      significantly favoured the pharmacy intervention versus the control group (0.96%;
      95% CI 0.71 to 1.22; p<0.001). Of the studies, 13 reported BMI kg/m2 in 1,827
      patients. The estimation of standardized absolute mean difference in reduction of
      BMI unit calculated through meta-analysis was 0.61 (95% CI 0.20 to 1.03; p=0.000)
      in favour of the pharmacy-intervention group. CONCLUSIONS: Pharmacy-based
      interventions have significant positive effects on controlling 2 major risks
      factors associated with diabetes-related complications: A1C levels and BMI.
      However, there is a dearth of evidence about the effects of pharmacy-based
      intervention on nonclinical outcomes, including healthcare utilization and
      quality of life.

PMID- 29224637
TI  - Valve hemodynamic deterioration and cardiovascular outcomes in TAVR: A report
      from the STS/ACC TVT Registry.
AB  - BACKGROUND: Recent reports of leaflet abnormalities (detected using advanced
      imaging) have raised questions regarding transcatheter aortic valve replacement
      (TAVR) durability. We sought to determine the incidence of valve hemodynamic
      deterioration (VHD) and its association with cardiovascular outcomes. METHODS AND
      RESULTS: Consecutive cases with paired postimplant and follow-up echocardiograms
      from November 2011 to March 2015 in the STS/ACC TVT Registry were allocated into
      2 overlapping cohorts: early (paired echocardiograms at 0 and 30 days) and late
      (paired echocardiograms at 30 days and 1 year). VHD was defined as an increase in
      mean aortic valve gradient >=10 mm Hg. Eighteen-month cardiovascular outcomes
      were determined via linkage with Centers for Medicare & Medicaid Services claims.
      Backwards selection logistic regression was performed to determine predictors of
      VHD. Among 10,099 TAVRs with paired echocardiograms, the median age was 84 years
      and 48.7% were female, with Society of Thoracic Surgeons score distributions of
      <8% (61.7%), 8%-15% (28.8%), and >15% (9.5%). The incidence of VHD was 2.1% in
      the early cohort and 2.5% in the late cohort. There was no significant difference
      between those with and without VHD in either cohort in the combined end point of
      death/stroke/aortic valve reintervention or heart failure hospitalization or
      myocardial infarction. Independent predictors of VHD included chronic lung
      disease, valve-in-valve procedure, 23-mm TAVR valve, severe patient-prosthesis
      mismatch, increasing body mass index, and increasing baseline aortic valve
      gradient. CONCLUSIONS: The incidence of VHD in US clinical practice is low, and
      VHD is not associated with increased cardiovascular events at 18 months. Patient
      and procedural predictors may help to identify patients at risk for VHD in whom
      surveillance or preventive strategies may be considered.

PMID- 29224638
TI  - Predictors of perioperative major bleeding in patients who interrupt warfarin for
      an elective surgery or procedure: Analysis of the BRIDGE trial.
AB  - BACKGROUND: The use of low-molecular weight heparin bridge therapy during
      warfarin interruption for elective surgery/procedures increases bleeding. Other
      predictors of bleeding in this setting are not well described. METHODS: BRIDGE
      was a randomized, double-blind, placebo-controlled trial of bridge therapy with
      dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring
      warfarin interruption. Bleeding outcomes were documented from the time of
      warfarin interruption until up to 37 days postprocedure. Multiple logistic
      regression and time-dependent hazard models were used to identify major bleeding
      predictors. RESULTS: We analyzed 1,813 patients of whom 895 received bridging and
      918 received placebo. Median patient age was 72.6 years, and 73.3% were male.
      Forty-one major bleeding events occurred at a median time of 7.0 days
      (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline
      predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a
      history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk
      procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9).
      Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure
      international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent
      predictors of major bleeding. Major bleeding was most common in the first 10 days
      compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). CONCLUSIONS: In
      addition to bridge therapy, perioperative aspirin use, postprocedure
      international normalized ratio >3.0, a history of renal failure, and having a
      high-bleeding risk procedure increase the risk of major bleeding around the time
      of an elective surgery/procedure requiring warfarin interruption.

PMID- 29224639
TI  - A multinational clinical approach to assessing the effectiveness of catheter
      based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study
      designs.
AB  - Catheter-based renal denervation is a new approach to treat hypertension via
      modulation of the renal sympathetic nerves. Although nonrandomized and small,
      open-label randomized studies resulted in significant reductions in office blood
      pressure 6months after renal denervation with monopolar radiofrequency catheters,
      the first prospective, randomized, sham-controlled study (Symplicity HTN-3)
      failed to meet its blood pressure efficacy end point. New clinical trials with
      new catheters have since been designed to address the limitations of earlier
      studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter,
      blinded, randomized, sham-controlled trials designed to assess the blood pressure
      lowering efficacy of the ultrasound-based renal denervation system (Paradise) in
      patients with established hypertension either on or off antihypertensive
      medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the
      United States and Europe. The SOLO cohort includes patients with essential
      hypertension, at low cardiovascular risk, and either controlled on 1 to 2
      antihypertensive medications or uncontrolled on 0 to 2 antihypertensive
      medications. Patients undergo a 4-week medication washout period before
      randomization to renal denervation (treatment) or renal angiogram (sham). The
      TRIO cohort includes patients with hypertension resistant to at least 3
      antihypertensive drugs including a diuretic. Patients will be stabilized on a
      single-pill, triple-antihypertensive-drug combination for 4weeks before
      randomization to treatment or sham. Reduction in daytime ambulatory systolic
      blood pressure (primary end point) will be assessed at 2months in both cohorts. A
      predefined medication escalation protocol, as needed for blood pressure control,
      is implemented between 2 and 6months in both cohorts by a study staff member
      blinded to the randomization process. At 6months, daytime ambulatory blood
      pressure and antihypertensive treatment score will be assessed. REQUIRE is
      designed to evaluate patients with resistant hypertension on standard of care
      medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood
      pressure will be assessed at 3months (primary end point). Both studies are
      enrolling patients, and their results are expected in 2018.

PMID- 29224640
TI  - Return to the workforce following infective endocarditis-A nationwide cohort
      study.
AB  - BACKGROUND: The ability to return to work after infective endocarditis (IE) holds
      important socioeconomic consequences for both patients and society, yet data on
      this issue are sparse. We examined return to the workforce and associated factors
      in IE patients of working age. METHODS: Using Danish nationwide registries, we
      identified 1,065 patients aged 18-60 years with a first-time diagnosis of IE
      (1996-2013) who were part of the workforce prior to admission and alive at
      discharge. RESULTS: One year after discharge, 765 (71.8%) patients had returned
      to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received
      disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6
      (0.6%) had emigrated. Factors associated with return to the workforce were
      identified using multivariable logistic regression. Younger age (18-40 vs 56-60
      years; odds ratio, 2.85; 95% CI, 1.71-4.76) and higher level of education (higher
      educational level vs basic school; 5.47, 2.05-14.6) and income (highest quartile
      vs lowest; 3.17, 1.85-5.46) were associated with return to the workforce. Longer
      length of hospital stay (>90 vs 14-30 days; 0.16, 0.07-0.38); stroke during IE
      admission (0.38, 0.21-0.71); and a history of chronic kidney disease (0.29, 0.11
      0.75), chronic obstructive pulmonary disease (0.31, 0.13-0.71), and malignancy
      (0.39, 0.22-0.69) were associated with a lower likelihood of returning to the
      workforce. CONCLUSIONS: Seven of 10 patients who were part of the workforce prior
      to IE and alive at discharge were part of the workforce 1 year later. Younger
      age, higher socioeconomic status, and absence of major comorbidities were
      associated with return to the workforce.

PMID- 29224641
TI  - Design of a bilevel clinical trial targeting adherence in heart failure patients
      and their providers: The Congestive Heart Failure Adherence Redesign Trial
      (CHART).
AB  - BACKGROUND: Socioeconomically disadvantaged patients are at an increased risk for
      adverse heart failure (HF) outcomes based upon nonadherence to medications and
      diet. Physicians are also suboptimally adherent to prescribing evidence-based
      therapy for HF. METHODS: Congestive Heart Failure Adherence Redesign Trial
      (CHART) (NCT01698242) is a multicenter, bilevel, cluster randomized behavioral
      efficacy trial designed to assess the impact of intervening simultaneously on
      physicians and their socioeconomically disadvantaged patients (annual income
      <$30,000) having HF with reduced ejection fraction. Treatment arm physicians
      received individualized feedback on their adherence to prescribing evidence-based
      therapy. Their patients received weekly home visits from community health workers
      aimed at promoting understanding of HF and integrating adherence into daily life.
      Control arm physicians received regular updates on advances in HF management, and
      patients received monthly HF educational tip sheets produced by the American
      Heart Association. The primary outcome was all-cause hospital days over 30
      months. RESULTS: A total of 72 physicians (treatment, 35; control, 37) and their
      320 patients (treatment, 157; control, 163) were recruited within 2 years.
      Randomization of physicians with all of their patients being assigned to the same
      arm was feasible and did not compromise the comparability of patients by arm.
      Using 5 recruiting hospitals located within disadvantaged neighborhoods produced
      a cohort that was primarily African American and representative of low-income
      urban patients with HF with reduced ejection fraction. CONCLUSION: CHART will
      determine the value of intervening on low adherence simultaneously in physicians
      and their socioeconomically disadvantaged patients in reducing all-cause
      hospitalization days.

PMID- 29224642
TI  - Drug-induced cardiac abnormalities in premature infants and neonates.
AB  - The Cardiac Safety Research Consortium (CSRC) is a transparent, public-private
      partnership that was established in 2005 as a Critical Path Program and
      formalized in 2006 under a Memorandum of Understanding between the United States
      Food and Drug Administration and Duke University. Our continuing goal is to
      advance paradigms for more efficient regulatory science related to the
      cardiovascular safety of new therapeutics, both in the United States and
      globally, particularly where such safety questions add burden to innovative
      research and development. This White Paper provides a summary of discussions by a
      cardiovascular committee cosponsored by the CSRC and the US Food and Drug
      Administration (FDA) that initially met in December 2014, and periodically
      convened at FDA's White Oak headquarters from March 2015 to September 2016. The
      committee focused on the lack of information concerning the cardiac effects of
      medications in the premature infant and neonate population compared with that of
      the older pediatric and adult populations. Key objectives of this paper are as
      follows: Provide an overview of human developmental cardiac electrophysiology, as
      well as the electrophysiology of premature infants and neonates; summarize all
      published juvenile animal models relevant to drug-induced cardiac toxicity;
      provide a consolidated source for all reported drug-induced cardiac toxicities by
      therapeutic area as a resource for neonatologists; present drugs that have a
      known cardiac effect in an adult population, but no reported toxicity in the
      premature infant and neonate populations; and summarize what is not currently
      known about drug-induced cardiac toxicity in premature infants and neonates, and
      what could be done to address this lack of knowledge. This paper presents the
      views of the authors and should not be construed to represent the views or
      policies of the FDA or Health Canada.

PMID- 29224643
TI  - Implications of the FDA approval of PCSK9 inhibitors and FOURIER results for
      contemporary cardiovascular practice: An NCDR Research to Practice (R2P) project.

PMID- 29224644
TI  - The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe
      aortic stenosis (AVATAR trial): A protocol update.

PMID- 29224645
TI  - Global geographical variation in patient characteristics in percutaneous coronary
      intervention clinical trials: A systematic review and meta-analysis.
AB  - BACKGROUND: We sought to determine whether there are differences in enrolled
      patients' risk factors in published percutaneous coronary intervention (PCI)
      trials between various continents. METHODS: We systematically identified clinical
      trials evaluating PCI interventions through PubMed. We reviewed 701 studies
      between 1990 and 2014 from North America (N=135), Europe (N=403), and Asia
      (N=163), examining the prevalence of cardiovascular risk factors-hypertension
      (HTN), diabetes mellitus (DM), hyperlipidemia (HL), smoking, sex, and body mass
      index. We performed meta-regression with random- and mixed-effects models to
      compare patient baseline characteristics between continents and linear meta
      regression analysis to test trends over time. RESULTS: In meta-regression with
      random-effects model, North American trials recruited the lowest proportion of
      male participants (71.32%), followed by Asian (74.41%) and European trials
      (76.47%; P<.0001). North American trials enrolled the highest proportion of
      patients with HTN (63.17%, P=.0035) and HL (63.72%, P<.0001), whereas Asia
      enrolled the highest proportion of DM patients (29.64%, P<.0001) and smoking
      (38.41%, P=.0144). When adjusting for other moderators such as publication date,
      body mass index, and sex in meta-regression with mixed-effects model, age was
      significantly positively correlated with HTN, HL, DM, and smoking (P<.001). Body
      mass index was significantly higher in Europe and North America than in Asia. All
      enrollment risk factors demonstrated (beta<0.02) statistically significant
      temporal trends over time, except for sex. CONCLUSIONS: There are major
      continental differences in risk factors among patients enrolled in PCI trials
      from various continents. Clinical trial results may not be applicable to patient
      populations from another region.

PMID- 29224646
TI  - Association of insurance type with receipt of oral anticoagulation in insured
      patients with atrial fibrillation: A report from the American College of
      Cardiology NCDR PINNACLE registry.
AB  - BACKGROUND: It is poorly understood whether insurance type may be a major
      contributor to the underuse of oral anticoagulation (OAC) among patients with
      atrial fibrillation (AF), particularly for novel oral anticoagulants (NOACs).
      METHODS: We performed a retrospective cohort registry study of patients with
      insurance, AF, CHA2DS2-VASc >=2, and at least one outpatient encounter recorded
      in the ACC NCDR's PINNACLE Registry between January 1, 2011 and December 31,
      2014. We used hierarchical regression, adjusting for patient characteristics and
      clustering by physician, to evaluate the association of insurance type (Private,
      Military, Medicare, Medicaid, Other) with receipt of OAC (any OAC, warfarin, or
      NOAC). RESULTS: In 363,309 patients (age 75+/-10; 48% female), we found a
      significant difference in proportions of OAC and NOAC prescription across
      insurance types (OAC: Military 53%, Private 53%, Medicare 52%, Other 41%,
      Medicaid 41%, P<.001; NOAC: Military 24%, Private 19%, Medicare 17%, Other 17%,
      Medicaid 8%, P<.001). After adjustment for patient characteristics and facility,
      private, Medicaid, and other insurance were independently associated with a lower
      odds of OAC prescription relative to Medicare, but military insured patients were
      not significantly different. After adjustment, military and private insurance
      were independently associated with a higher odds of NOAC prescription relative to
      Medicare, while Medicaid and other insurance were associated with a lower odds of
      NOAC prescription. CONCLUSIONS: In a contemporary US AF population, there was
      significant variation of OAC prescription across insurance plans, with the
      highest among private and Medicare insured patients. These differences may
      indicate that insurance plan, and its associated pharmacy benefits, affect the
      pace of diffusion of new therapies.

PMID- 29224647
TI  - Mineralocorticoid receptor antagonists in patients with acute myocardial
      infarction - A systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: Although mineralocorticoid antagonists (MRAs) reduce mortality in
      patients with heart failure complicating myocardial infarction (MI), it is
      unclear if they could be beneficial to all patients with MI. To evaluate the
      utility of MRAs in MI patients, we performed a systematic review and meta
      analysis. METHODS: MEDLINE, EMBASE, and Cochrane CENTRAL were searched from 1965
      to June 2016. Conference abstracts were searched from 2000 to June 2016.
      Randomized trials evaluating the effect of MRA after MIs were included. Two
      reviewers independently extracted data and assessed study quality. Data were
      combined using fixed-/random-effects models. RESULTS: Eleven randomized clinical
      trials (N = 11,258) were included; 1 trial (N = 6,642) included patients with
      apparent heart failure (Killip class III-IV). Administration of MRA versus
      placebo or standard therapy (no-MRA) after MI reduced overall and cardiovascular
      mortality (odds ratio [OR] 0.82, 95% CI 0.73-0.93, P = .002, and OR 0.82, 95% CI
      0.71-0.93, P = .003, respectively; I2 for both = 0%). In the subgroup of trials
      with patients with heart failure, the mortality was 14.4% in MRA group versus
      16.7% in no-MRA group (OR 0.84, 95% CI 0.73-0.96), and among those without heart
      failure, it was 2.5% with MRA versus 3.5% without MRA (OR 0.72, 95% CI 0.51-1.02,
      P for interaction = .43). Patients receiving MRA had fewer new or worsening heart
      failure events (OR 0.74, 95% CI 0.66-0.84, P < .0001; I2 = 14%). Nevertheless,
      MRA therapy increased risk for hyperkalemia (>=5.5 mmol/L) (OR 2.52, 95% CI 1.36
      4.65, P = .003; I2 = 63%). CONCLUSIONS: Administration of MRA may reduce
      mortality after acute MI. However, this is largely based on post-MI patients with
      heart failure. Further data are needed in MI patients without heart failure.

PMID- 29224648
TI  - Effect of high-dose oral multivitamins and minerals in participants not treated
      with statins in the randomized Trial to Assess Chelation Therapy (TACT).
AB  - IMPORTANCE: In a prespecified subgroup analysis of participants not on statin
      therapy at baseline in the TACT, a high-dose complex oral multivitamins and
      multimineral regimen was found to have a large unexpected benefit compared with
      placebo. The regimen tested was substantially different from any vitamin regimen
      tested in prior clinical trials. OBJECTIVE: To explore these results, we
      performed detailed additional analyses of participants not on statins at
      enrollment in TACT. DESIGN: TACT was a factorial trial testing chelation
      treatments and a 28-component high-dose oral multivitamins and multiminerals
      regimen versus placebo in post-myocardial infarction (MI) patients 50 years or
      older. PARTICIPANTS: There were 460 (27%) of 1,708 TACT participants not taking
      statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%)
      were in the placebo group. SETTING: Patients were enrolled at 134 sites around
      the United States and Canada. INTERVENTION: Daily high-dose oral multivitamins
      and multiminerals (6 tablets, active or placebo). MAIN OUTCOME: The primary end
      point of TACT was time to the first occurrence of any component of the composite
      end point: all-cause mortality, MI, stroke, coronary revascularization, or
      hospitalization for angina. RESULTS: The primary end point occurred in 137
      nonstatin participants (30%), of which 51 (23%) of 224 were in the active group
      and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence
      interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a
      combination of cardiovascular mortality, stroke, or recurrent MI, was consistent
      in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence
      interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with
      these results. CONCLUSION AND RELEVANCE: High-dose oral multivitamin and
      multimineral supplementation seem to decrease combined cardiac events in a
      stable, post-MI population not taking statin therapy at baseline. These
      unexpected findings are being retested in the ongoing TACT2.

PMID- 29224649
TI  - Efficacy and safety of potent platelet P2Y12 receptor inhibitors in elderly
      versus nonelderly patients with acute coronary syndrome: A systematic review and
      meta-analysis.
AB  - BACKGROUND: The use of the potent oral P2Y12 inhibitors prasugrel and ticagrelor
      in patients with acute coronary syndromes (ACS) has a favorable net clinical
      effect compared with clopidogrel and is recommended as first-line therapy.
      However, the impact of these agents on ischemic and bleeding events in elderly
      ACS patients is not well defined. METHODS: We performed a systematic review of
      articles comparing potent P2Y12 inhibitors to clopidogrel in elderly and
      nonelderly patients (defined according to each study) with ACS in terms of
      efficacy (composite of cardiovascular death, myocardial infarction, or stroke)
      and safety (major bleeding) end points. RESULTS: A total of 7,860 elderly and
      37,857 nonelderly patients from 7 studies (5 randomized control trials and 2
      observational studies) were included. Potent P2Y12 inhibitors significantly
      reduced efficacy end point in nonelderly patients (relative risk [RR] 0.85, 95%
      CI 0.79-0.93) and less so in elderly patients (RR 0.95, 95% CI 0.86-1.05). No
      significant differences were found between potent P2Y12 inhibitors and
      clopidogrel in terms of safety end point in both elderly (RR 1.19, 95% CI 0.95
      1.49) and nonelderly patients (RR 1.16, 95% CI 0.95-1.41). There were no
      significant interactions between age and treatment effect in both analyses
      (efficacy Pint=.16; safety Pint=.83). CONCLUSIONS: The effect of more potent
      P2Y12 inhibitors compared with clopidogrel on efficacy and safety end points is
      consistent in elderly and younger patients. These data imply that potent P2Y12
      inhibitors should not be withheld from eligible patients solely because of
      advanced age.

PMID- 29224650
TI  - Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a
      meta-analysis.
AB  - BACKGROUND: Chocolate consumption has been inconsistently associated with risk of
      atrial fibrillation (AF). We investigated the association between chocolate
      consumption and risk of AF in Swedish adults from two cohort studies and
      conducted a meta-analysis to summarize available evidence from cohort studies on
      this topic. METHODS: Our study population comprised 40,009 men from the Cohort of
      Swedish Men and 32,486 women from the Swedish Mammography Cohort. Incident AF
      cases were ascertained through linkage with the Swedish National Patient
      Register. Published cohort studies of chocolate consumption in relation to risk
      of AF were identified by a PubMed search through September 14, 2017. RESULTS:
      During a mean follow-up of 14.6 years, AF was diagnosed in 9978 Swedish men and
      women. Compared with non-consumers, the multivariable hazard ratio of AF for
      those in the highest category of chocolate consumption (>=3-4 servings/week) was
      0.96 (95% CI 0.88-1.04). In a random-effects meta-analysis of 5 cohort studies,
      including 180,454 participants and 16,356 AF cases, the hazard ratios of AF were
      0.97 (95% CI 0.94-1.01) per 2 servings/week increase in chocolate consumption and
      0.96 (95% CI 0.90-1.03) for the highest versus lowest category of chocolate
      consumption. CONCLUSION: Available data provide no evidence of an association of
      chocolate consumption with risk of AF.

PMID- 29224651
TI  - Role of Doppler echocardiography for cardiac output assessment in Fontan
      patients.
AB  - BACKGROUND: To determine (1) correlation between Doppler stroke volume index
      (SVI) and cardiac magnetic resonance imaging (CMRI) SVI and (2) association
      between Doppler SVI and Fontan-associated diseases (FAD) and Fontan failure.
      METHODS: Review of Fontan patients who underwent same-day CMRI and transthoracic
      echocardiography (TTE), 2005 to 2015. We defined FAD as cardiac thrombus, protein
      losing enteropathy, arrhythmia, and hospitalization for heart failure. Fontan
      failure was defined as Fontan conversion or revision, heart transplantation or
      listing, or death. RESULTS: Fifty-three patients with systemic left ventricle
      (LV) underwent 86 sets of TTE/CMRI. Mean (SD) age 31 (6) years. SVI (45 [16] vs
      42 [13] mL/m2), CI (3.0 [1.1] vs 2.8 [0.8] L min-1 m-2), and ejection fraction
      (53 [4]% vs 51 [5]%) were similar for both modalities (P>.05 for all). Doppler
      SVI correlated with CMRI (r=0.68; P<.001). Sixteen patients had cirrhosis, and
      these patients had a higher CI (3.9 [0.9] vs 2.8 [1.0] L min-1 m-2; P<.01). Among
      the 37 patients without cirrhosis, Doppler SVI <39 mL/m2 was associated with FAD
      (odds ratio [OR], 2.11; 95% confidence limit, 1.26-3.14; P=.02); Fontan failure
      was more common in patients with CI was <2.5 L min-1 m-2 (3/9 [33%] vs 0/28 [0%],
      P=.01). Another 11 patients with systemic right ventricle (RV) underwent 17 sets
      of TTE/CMRI, mean (SD) age 17 (3) years, and CMRI SVI also correlated with
      Doppler SVI (r=0.75; P<.001). CONCLUSION: Doppler SVI correlated with CMRI SVI in
      patients with systemic LV and systemic RV. The association between output
      measures (SVI and CI) and FAD were seen only in single LV patients (single RV
      patients not assessed for this outcome due to small numbers). An association
      between low Doppler CI and Fontan failure was suggested in a small number of
      single LV patients.

PMID- 29224652
TI  - Primary percutaneous coronary intervention at centers with and without on-site
      surgical support: Insights from the Blue Cross Blue Shield of Michigan
      Cardiovascular Consortium (BMC2).
AB  - BACKGROUND: Primary percutaneous coronary intervention (PPCI) is being
      increasingly performed nationally at sites without on-site cardiac surgery;
      however, recent guidelines only provide a Class IIa recommendation for this
      practice. The state of Michigan has permitted PPCI without on-site surgery under
      a closely monitored system that mandates auditing of all procedures and quarterly
      feedback on quality and outcomes. This study sought to compare outcomes of
      patients undergoing PPCI at centers with and without on-site surgery in the state
      of Michigan. METHODS: Consecutive patients who underwent PPCI at 47 hospitals in
      Michigan from January 2010 to December 2015 were included. From this cohort,
      4,091 patients from sites with and without on-site cardiac surgery were
      propensity matched in a 1:1 fashion to compare baseline characteristics,
      procedural details, and in-hospital outcomes. RESULTS: Of the 25,886 PPCIs
      performed at 47 hospitals in Michigan from 2010 to 2015, 21,610 (83.5%) were
      performed at sites with on-site surgery and 4,276 (16.5%) at sites without on
      site surgery. Using propensity score matched cohorts (4,091 patients for each
      site type), we found no significant differences in baseline characteristics.
      Overall mortality (5.4% vs 5.8%; P=.442); composite outcome of in-hospital
      mortality, contrast-induced nephropathy, bleeding, and stroke (13.8% vs 12.8%;
      P=.152); and individual outcomes within the composite group showed no significant
      differences. Additionally, there were no clinically meaningful differences in
      rates of urgent/emergent coronary artery bypass graft or length of stay.
      Significant differences, however, were found in procedural access site,
      antiplatelet therapy, contrast volume, and anticoagulant strategy. CONCLUSIONS:
      Primary PCI performed at centers with and without cardiac surgery have comparable
      outcomes and complication rates when performed with close monitoring of quality
      and outcomes.

PMID- 29224653
TI  - Introduction.

PMID- 29224654
TI  - Evaluation and Management of Blunt Solid Organ Trauma.
AB  - Trauma is a leading cause of death in patients under the age of 45 and generally
      associated with a high kinetic energy event such as a motor vehicle accident or
      fall from extreme elevations. Blunt trauma can affect every organ system and
      major vascular structure with potentially devastating effect. When we consider
      abdominal solid organ injury from blunt trauma, we usually think of the liver,
      spleen, and kidneys. However, all of the abdominal organs, including the pancreas
      and adrenal glands, may be involved. Blunt hepatic trauma is more commonly
      associated with venous bleeding rather than arterial injury. Stable venous injury
      is often managed conservatively; when the patient is hemodynamically unstable
      from venous hepatic injury, operative management should be first-line therapy.
      When the injury is arterial, endovascular therapy should be initiated. Blunt
      trauma to the spleen is the most common cause of traumatic injury to the spleen.
      Management is controversial. In our institution unstable patients are taken to
      the operating room, and stable patients with Grades IV-V injuries and patients
      with active arterial injury are taken for endovascular treatment. Renal injuries
      are less common, and evidence of arterial injury such as active extravasation or
      pseudoaneurysm is warranted before endovascular therapy. Pancreatic trauma is
      uncommon and usually secondary to steering wheel/handlebar mechanism injuries.
      Adrenal injuries are rare in the absence of megatrauma or underlying adrenal
      abnormality.

PMID- 29224655
TI  - Evaluation and Treatment of Blunt Pelvic Trauma.
AB  - Trauma is a significant contributor to mortality, especially in the young. Pelvic
      trauma with pelvic ring fractures may result in associated arterial injury,
      necessitating endovascular intervention. As a result, interventional radiology
      plays a critical role in partnering with trauma providers in the care of these
      patients. Management is determined by the acuity of the patient's clinical
      status, radiographs, ultrasound, and the results of computed tomography imaging
      when available. Numerous embolic agents are available for treatment of arterial
      hemorrhage.

PMID- 29224656
TI  - Emergent Endovascular Treatment of Penetrating Trauma: Solid Organ and Extremity.
AB  - Penetrating injuries can result in acute or subacute arterial injuries of the
      solid organs or extremities. Although most penetrating injuries are managed
      conservatively, some patients require endovascular or surgical treatment. Often,
      the best method for management is controversial and the level of urgency for
      clinical decision-making is high. Once the decision has been made to intervene,
      the operator must also determine the best embolization material and technique to
      use. Not unfrequently, these decisions are made during the course of the
      procedure. There are numerous embolization agents, each of which serves a very
      specific purpose, depending on the clinical scenario. Within this article, we
      will review endovascular treatment indications, contraindications, and
      endovascular techniques for the treatment of penetrating trauma of the solid
      organs or extremities.

PMID- 29224657
TI  - CTA As an Adjuvant Tool for Acute Intra-abdominal or Gastrointestinal Bleeding.
AB  - Hematemesis and acute postsurgical upper gastrointestinal hemorrhage are common
      emergent on-call consultations for the interventional radiologist. Upper GI
      bleleding (UGIB) is a relatively frequent problem. The incidence and mortality
      vary among patient populations, but studies have shown an overall incidence
      ranging from 36-172 cases per 100,000 adults per year, with a mortality rate of
      5%-14%. The incidence is significantly higher in men. Peptic ulcer disease is the
      predominant etiology, responsible for 28%-59% of UGIB. Other causes include
      varices, mucosal erosive disease, Mallory-Weiss syndrome, and malignancy. After
      assessment of hemodynamic status and airway stability with resuscitative efforts
      as needed, initial consultation with gastroenterology for endoscopic evaluation
      and treatment is well regarded as the initial therapeutic strategy. Angiography
      with embolization and interventional techniques directed at managing variceal
      hemorrhage have emerged as very capable second-line strategies for patients who
      have failed endoscopic therapy. In certain circumstances, the interventional
      radiologist may be called upon as the first line, notably for patients who have
      had recent surgical intervention or who have extraluminal hemorrhage. As the role
      of the interventional radiologist in the evaluation and treatment of UGIB
      continues to evolve, familiarity and knowledge of how to deal with these urgent
      and emergent clinical scenarios becomes paramount.

PMID- 29224658
TI  - Management of Acute Lower Gastrointestinal Bleeding.
AB  - Acute lower gastrointestinal bleeding (LGIB), defined as hemorrhage into the
      gastrointestinal tract distal to the ligament of Treitz, is a major cause of
      morbidity and mortality among adults. Overall, mortality rates are estimated
      between 2.4% and 3.9%. The most common etiology for LGIB is diverticulosis,
      implicated in approximately 30% of cases, with other causes including
      hemorrhoids, ischemic colitis, and postpolypectomy bleeding. Transcatheter
      visceral angiography has begun to play an increasingly important role in both the
      diagnosis and treatment of LGIB. Historically, transcatheter visceral angiography
      has been used to direct vasopressin infusion with embolization reserved for
      treatment of upper gastrointestinal bleeding. However, advances in microcatheter
      technology and embolotherapy have enabled super-selective embolization to emerge
      as the treatment of choice for many cases of LGIB.

PMID- 29224659
TI  - Bronchial Artery Embolization for the Treatment of Acute Hemoptysis.
AB  - Massive hemoptysis is a life-threatening condition often defined as coughing up
      300-600mL of blood in 24 hours in an adult, or >8mL/kg in 24 hours in a child.
      Although the definition is controversial, one should view massive hemoptysis as
      any volume of expectorated blood that can cause respiratory failure. This is
      because mortality in the setting of hemoptysis is usually associated with
      asphyxiation, rather than exsanguination. Massive hemoptysis accounts for only
      about 5% of cases of hemoptysis, but when treated conservatively, has a reported
      mortality rate between 50% and 85%. Etiologies vary widely based on demographics.
      In children, infectious causes predominate in developing countries, and cystic
      fibrosis predominates among children of European descent. In adults, malignancy,
      bronchiectasis, and chronic infection are the most common causes. Treatment
      begins with resuscitation and airway protection, followed by minimally invasive
      bronchoscopic and endovascular techniques. Surgical interventions are considered
      last line therapy due to mortality rates of 37%-43% in the setting of massive
      hemoptysis. Bronchial artery embolization is now considered the treatment of
      choice for massive hemoptysis.

PMID- 29224660
TI  - Postpartum Hemorrhage.
AB  - Interventional radiologists are often called for emergent control of abnormal
      uterine bleeding. Bleeding, even heavy bleeding as a result of uterine fibroids
      is not a common emergent procedure; instead, pregnancy and pregnancy related
      conditions, trauma and malignancy associated with bleeding can be the source of
      many interventional radiology on call events or procedures. Postpartum hemorrhage
      (PPH) is the most common cause, and is defined as blood loss of 500mL after
      vaginal delivery or 1000mL after cesarean section. Several authors have suggested
      a simpler definition of any amount of blood loss that creates hemodynamic
      instability in the mother. Regardless, PPH can be a life-threatening emergency
      and is a leading cause of maternal mortality requiring prompt action. Primary PPH
      is bleeding within the first 24 hour of delivery and secondary PPH is hemorrhage
      that occurs more than 24 hour after delivery. In addition to death, other serious
      morbidity resulting from postpartum bleeding includes shock, adult respiratory
      distress syndrome, coagulopathy, and loss of fertility due to hysterectomy.
      Transcatheter uterine artery embolization was first introduced as a treatment for
      PPH in 1979. It is a nonsurgical, minimally invasive, extremely safe and
      effective treatment for controlling excessive bleeding of the female reproductive
      track usually after conservative measures have failed, yet somewhat underused.
      Referring providers have limited awareness of the procedure. In hospitals where
      interventional radiologists have the experience and technical expertise to
      perform pelvic arteriography and embolization, this therapeutic option can play a
      pivotal role in the management of emergent obstetric hemorrhage.

PMID- 29224661
TI  - Acute Limb Ischemia.
AB  - Acute limb ischemia is technically defined as ischemia of the lower extremities
      lasting 14 days or less. The condition affects between 15 and 26 persons per
      100,000 each year in the United States. The associated morbidity and mortality is
      extremely high, with 1-year mortality rates reported at over 40%. Acute limb
      ischemia is 20 times more common in the lower extremities than the upper
      extremities. Both interventional radiologists and vascular surgeons bring unique
      skills to the table in caring for these patients, and therefore should approach
      the care of these patients in a multidisciplinary manner to ensure the best
      outcomes for each patient. Patients should be classified according to the
      Rutherford classification scale for acute limb ischemia. Catheter-directed
      thrombolysis can be a viable treatment alternative for these patients, offering a
      minimally invasive option to patients with outcomes similar to surgery. It is
      important to know the presentation, physical examination, risks and benefits, as
      well as the techniques and equipment required to treat patients with acute lower
      limb ischemia.

PMID- 29224662
TI  - Managing Venous Thromboembolic Disease On-Call.
AB  - Managing venous thromboembolic disease on-call requires the interventional
      radiologist consider not only potential risk and benefit to the patient but also
      available resources in the IR suite as well as throughout the hospital, such as
      intensive care monitoring during treatment. We demonstrate how our practice
      manages these on-call cases ranging from deep venous thrombosis to acute
      pulmonary embolism and decide which patients need emergent treatment and which
      can undergo delayed intervention during working hours. In all cases, an adequate
      preprocedural clinical assessment is crucial.

PMID- 29224664
TI  - Preface - Part 2: Circadian and endocrine rhythms.

PMID- 29224663
TI  - Obstruction of the Biliary and Urinary System.
AB  - Biliary and urinary obstructions can be managed endoscopically or
      cystoscopically, surgically or by percutansous intervention or drainage. If the
      obtructed system is infected, emergent decompression is needed. Early recognition
      and treatment is paramount in both conditions. Acute cholangitis can present many
      different ways, from mild symptoms to fulminant sepsis. It is usually a result of
      ascending bacterial colonization and biliary obstruction resulting in bacterial
      overgrowth. Therefore, those patients with recent biliary instrumentation or
      previous biliary modification are at higher risk. Charcot's triad of fever, right
      upper quadrant abdominal pain, and jaundice is only seen in 50%-70% of patients.
      Fever is seen in over 90% of cases, pain is seen in 70% of cases, and jaundice is
      seen in 60% of cases. Altered mental status and hypotension are associated with
      severe cases. All 5 symptoms of fever, right upper quadrant abdominal pain,
      jaundice, altered mental status, and hypotension are referred to as Reynold's
      Pentad. Acute pyonephrosis can also present many different ways, from minimal
      symptoms to fulminant sepsis. Fever, chills, and flank pain are the classic
      symptoms, although some patients may be relatively asymptomatic. Pyonephrosis may
      present with a classic triad of fever, flank pain, and hydronephrosis, or simply
      hydronephrosis and sepsis. Pyonephrosis usually occurs as a result of urinary
      obstruction with either an ascending infection of the urinary tract or
      hematogenous spread of a bacterial pathogen as the culprit. Up to 75% of cases
      are related to urinary stone disease. Patients are at increased risk for
      pyonephrosis when they haven anatomic urinary tract obstruction, certain chronic
      diseases (diabetes meliitus and AIDS), or are immunosuppressed due to
      immunodeficiency or medications, (chronic steroid therapy).

PMID- 29224665
TI  - Endocrine rhythms of growth hormone release: Insights from animal studies.
AB  - Growth hormone (GH) secretory patterns emerge following birth, and changes in
      patterning occur throughout life. These secretory patterns are coupled to growth,
      reproduction and metabolism. Comparing human and animal studies, this review will
      highlight ultradian patterning of GH release and the mechanisms that contribute
      to this. Discussions will focus on the emergence in variations in the number and
      frequency of GH secretory events, and the amounts of GH released (peak and
      basal). Animal studies have contributed significantly to our understanding of the
      processes that regulate GH release. However, translation of knowledge from animal
      models to benefit our understanding of human physiology is sometimes limited. To
      overcome these limitations, it is critical that we reconcile the cause and
      consequences of differences in GH release between humans and model organisms. In
      doing so, we can embrace emerging technologies that will rapidly advance our
      knowledge of endogenous process that control GH release.

PMID- 29224666
TI  - Central and peripheral roles of vasopressin in the circadian defense of body
      hydration.
AB  - Vasopressin is a neuropeptide synthesized by specific subsets of neurons within
      the eye and brain. Studies in rats and mice have shown that vasopressin produced
      by magnocellular neurosecretory cells (MNCs) that project to the neurohypophysis
      is released into the blood circulation where it serves as an antidiuretic hormone
      to promote water reabsorption from the kidney. Moreover vasopressin is a
      neurotransmitter and neuromodulator that contributes to time-keeping within the
      master circadian clock (i.e. the suprachiasmatic nucleus, SCN) and is also used
      as an output signal by SCN neurons to direct centrally mediated circadian
      rhythms. In this chapter, we review recent cellular and network level studies in
      rodents that have provided insight into how circadian rhythms in vasopressin
      mediate changes in water intake behavior and renal water conservation that
      protect the body against dehydration during sleep.

PMID- 29224667
TI  - The hormone melatonin: Animal studies.
AB  - The Melatonin (MLT), secreted rhythmically by the pineal, is an efferent hormonal
      signal of the circadian clock. MLT presents overall pleitropic effects but it is
      the role of MLT as a hormonal circadian signal which is the best documented. MLT
      receptors are present in numerous structures/organs and the MLT is now considered
      as an endogenous synchronizer within the circadian system. The presence of MLT
      receptors within the circadian clock, explains that exogenous MLT is a
      chronobiotic drug. Trials in humans, have confirmed the efficacy of MLT in
      circadian rhythm disorders. Subtypes of MLT-receptors have been characterized
      (MT1 and MT2). Striking differences are observed in the distribution pattern of
      these 2 subtypes. Up to now, MTL-analogues commercialized as drugs, are all non
      specific MT1/MT2 agonists acting on the SCN. The development of new specific
      agonists/antagonists for both subtypes, the identification of the link between
      MLT target sites within different parts of the brain or the body and the
      association of specific MLT receptor subtypes and particular physiological
      effects open great therapeutic potential.

PMID- 29224668
TI  - Circadian clock-gastrointestinal peptide interaction in peripheral tissues and
      the brain.
AB  - Food intake and sleep are two mutually exclusive behaviors and both are normally
      confined to opposing phases of the diurnal cycle. The temporal coordination of
      behavior and physiology along the 24-h day-night cycle is organized by a network
      of circadian clocks that orchestrate transcriptional programs controlling
      cellular physiology. Many of the peptide hormones of the gastrointestinal tract
      are not only secreted in a circadian fashion, they can also affect circadian
      clock function in peripheral metabolic tissues and the brain, thus providing
      metabolic feedback to metabolic and neurobehavioral circuits. In this review, we
      summarize the current knowledge on this gastrointestinal peptide crosstalk and
      its potential role in the coordination of nutrition and the maintenance of
      metabolic homeostasis.

PMID- 29224669
TI  - Circadian aspects of adipokine regulation in rodents.
AB  - Most hormones display daily fluctuations of secretion during the 24-h cycle. This
      is also the case for adipokines, in particular the anorexigenic hormone, leptin.
      The temporal organization of the endocrine system is principally controlled by a
      network of circadian clocks. The circadian network comprises a master circadian
      clock, located in the suprachiasmatic nucleus of the hypothalamus, synchronized
      to the ambient light, and secondary circadian clocks found in various peripheral
      organs, such as the adipose tissues. Besides circadian clocks, other factors such
      as meals and metabolic status impact daily profiles of hormonal levels. In turn,
      the precise daily pattern of hormonal release provides temporal signaling
      information. This review will describe the reciprocal links between the circadian
      clocks and rhythmic secretion of leptin, and discuss the metabolic impact of
      circadian desynchronization and altered rhythmic leptin.

PMID- 29224670
TI  - Editorial: Determinants of mammalian feeding system design.

PMID- 29224671
TI  - Systemic lupus erythematosus.

PMID- 29224672
TI  - SLE redefined on the basis of molecular pathways.
AB  - The implementation of precision medicine requires the recruiting of patients in
      statistically enough numbers, the possibility of obtaining enough materials, and
      the integration of data from various platforms, which are all real limitations.
      These types of studies have been performed extensively in cancer but barely on
      systemic lupus erythematosus (SLE) or other rheumatic diseases. To consider the
      practical use of the information obtained from such studies, we have to take into
      account the best biological fluid to use, the ease to perform the analysis in
      clinical practice, and its relevance to clinical practice. Here we review the
      most relevant studies that have performed analyses that attempt to classify or
      stratify SLE. We focus on two types of studies: those that stratify individuals
      diagnosed with SLE and those that compare SLE with other autoimmune diseases,
      defining differences and similarities that may be clinically relevant in the
      future.

PMID- 29224674
TI  - Drivers of the immunopathogenesis in systemic lupus erythematosus.
AB  - This review summarises a number of current insights into the pathogenesis of SLE.
      On the basis of the interaction of environmental factors within a predisposed
      host, a chronic autoimmune process gains function with a positive feed-forward
      loop between innate and adaptive immunity. A current focus of SLE pathogenesis is
      on the enhanced production of certain cytokines, such as type I interferons and
      BLyS/BAFF, suggesting continuous plasmacytoid dendritic and myeloid cell activity
      together with disturbances of B lineage cells (increased autoantibodies,
      including anti-dsDNA and plasmablasts, which correlate with SLE activity and
      memory B-cell abnormalities). Recent studies provided evidence that CD4+ and CD8+
      T cells and B cells are hyporesponsive in SLE, likely reflecting their 'post
      activation status'. Data of enhanced protein tyrosine phosphatase activity of
      lymphocytes in SLE require consideration if they represent a disease
      characteristic. Better understanding of the chronic autoimmune phase is needed in
      addition to those phases during flares and will permit improved treatment of SLE.

PMID- 29224675
TI  - Mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid
      syndrome.
AB  - The presence of antiphospholipid antibodies is one of the most common acquired
      risk factors for thrombosis. Antiphospholipid antibodies is a collective term for
      a set of autoantibodies with closely related but different specificity.
      Experiments in which isolated patient antibodies were injected into mice have
      shown that a specific subset of autoantibodies, those directed against the first
      domain of plasma protein beta2-glycoprotein I, can explain the increased risk of
      thrombosis. Experiments performed with these mice have shown that autoantibodies
      against beta2-glycoprotein I bind to and activate cells such as endothelial
      cells, monocytes, and platelets. Activation of these cells, all involved in the
      regulation of hemostasis, results in a shift towards a prothrombotic state. How
      this process is regulated, whether this is the only mechanism involved, and
      whether this is the only subpopulation responsible for the increased thrombotic
      risk is unknown. In this review, we will critically discuss what is known and
      what is debatable on the pathophysiology of antiphospholipid syndrome.

PMID- 29224673
TI  - Understanding the role of environmental factors in the development of systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disease with a complex
      etiology. Its risk is higher among women, racial and ethnic minorities, and
      individuals with a family history of SLE or related autoimmune diseases. It is
      believed that genetic factors interact with environmental exposures throughout
      the lifespan to influence susceptibility to developing SLE. The strongest
      epidemiologic evidence exists for increased risk of SLE associated with exposure
      to crystalline silica, current cigarette smoking, use of oral contraceptives, and
      postmenopausal hormone replacement therapy, while there is an inverse association
      with alcohol use. Emerging research results suggest possible associations of SLE
      risk with exposure to solvents, residential and agricultural pesticides, heavy
      metals, and air pollution. Ultraviolet light, certain infections, and
      vaccinations have also been hypothesized to be related to SLE risk. Mechanisms
      linking environmental exposures and SLE include epigenetic modifications
      resulting from exposures, increased oxidative stress, systemic inflammation and
      inflammatory cytokine upregulation, and hormonal effects. Research needs to
      include new studies of environmental risk factors for SLE in general, with a
      focus on lifetime exposure assessment. In addition, studies in susceptible
      subgroups, such as family members, studies based on genetic risk profiles, and
      studies in individuals with evidence of pre-clinical autoimmunity based on the
      detection of specific auto-antibodies are also required. Understanding the role
      of environmental exposures in the development of SLE may help identify modifiable
      risk factors and potential etiological mechanisms.

PMID- 29224676
TI  - Treat to target, remission and low disease activity in SLE.
AB  - Despite improvements in survival, outcomes of contemporary treatment of systemic
      lupus erythematosus (SLE) are unacceptable. Unlike in many diseases, treat-to
      target (T2T) approaches have not been adopted in SLE, owing to a lack of
      validated targets to treat towards. Therefore, it is a key goal to validate
      target state definitions such as low disease activity and remission, and test
      their implementation in clinical practice and clinical trials. In this article,
      we review recent advances in T2T approaches in SLE, and emerging evidence-based
      consensus on definitions of remission and low disease activity that are needed to
      underpin such approaches. We conclude that, while more work is needed, much has
      been achieved and at least for low disease activity the lupus low disease
      activity state definition appears to have utility and validity for the study of
      SLE. Application to routine clinical care awaits validation of improved outcomes
      from T2T studies based on these targets.

PMID- 29224678
TI  - Atherosclerosis in systemic lupus erythematosus.
AB  - Cardiovascular disease (CVD), comprising coronary heart disease and stroke, is
      one of the most important causes of death in patients with systemic lupus
      erythematosus (SLE). The risks of developing both clinical CVD and sub-clinical
      atherosclerosis are increased in patients with SLE. This increase is not fully
      explained by traditional cardiovascular risk factors such as smoking,
      hypertension and elevated cholesterol, and it is believed that immune dysfunction
      also contributes to CVD risk in SLE. In particular, recent studies have shown
      that abnormalities in both serum lipid profile and the autoantibody and T
      lymphocyte response to lipids may play a role in development of atherosclerosis.
      The standard CVD risk calculation algorithms based on traditional risk factors
      underestimate the risk of developing CVD in patients with SLE. Thus, novel
      algorithms incorporating new biomarkers such as pro-inflammatory high-density
      lipoprotein and use of imaging techniques such as carotid ultrasound scanning may
      become increasingly valuable.

PMID- 29224679
TI  - A review on SLE and malignancy.
AB  - Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease
      characterized by autoantibody production, complement activation, and immune
      complex deposition. It predominantly affects young and middle-aged women. While
      improvements in the diagnosis and treatment of SLE have altered prognosis,
      morbidity and mortality rates remain higher than the general population. In
      addition to renal injury, cardiovascular disease, and infection, malignancy is
      known to be a significant cause of death in this population. There is increasing
      evidence to suggest that patients with SLE have a slightly higher overall risk of
      malignancy. The risk of malignancy in SLE is of considerable interest because the
      immune and genetic pathways underlying the pathogenesis of SLE and the
      immunosuppressant drugs (ISDs) used in its management may mediate this altered
      risk. Our current understanding of these and other risk factors and the
      implications for treating SLE and screening for malignancy is still evolving.
      This review summarizes the association between SLE and malignancy. The first
      section discusses the risk of overall and site-specific malignancies in both
      adult- and pediatric-onset SLE. Next, we evaluate the risk factors and possible
      mechanisms underlying the link between malignancy and SLE, including the use of
      ISDs, presence of certain SLE-related autoantibodies, chronic immune
      dysregulation, environmental factors, and shared genetic susceptibility. Finally,
      we review guidelines regarding cancer screening and vaccination for human
      papilloma virus.

PMID- 29224677
TI  - Diagnostic and prognostic tests in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease
      characterized by autoantibodies directed against numerous self-nuclear antigens.
      Because of the heterogeneous nature of lupus, it has been challenging to identify
      markers that are sensitive and specific enough for its diagnosis and monitoring.
      However, with the sequencing of the human genome, rapid development of high
      throughput approaches has allowed for a better understanding of the
      etiopathogenesis of complex diseases, including SLE. Here we present a review of
      the latest advancements in biomarker discovery during the "omics" era, using
      these novel technologies, for assisting in the diagnosis and prognosis of
      patients with SLE.

PMID- 29224680
TI  - Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease
      with a high prevalence in females of childbearing age. Pregnancy in SLE nowadays
      has favorable outcomes for the majority of women. However, flares of disease
      activity, preeclampsia, fetal loss, and preterm birth are well-known risks in
      such pregnancies. Anti-SS-A(Ro)/SS-B(La) antibodies put fetuses at risk for
      congenital heart block and neonatal lupus. Several risk factors for adverse
      pregnancy outcomes have been identified. Women with antiphospholipid antibodies
      or antiphospholipid syndrome and lupus nephritis represent a group with high risk
      for obstetric complications. Factors such as appropriate preconception counseling
      and medication adjustment, strict disease control prior to pregnancy, and
      intensive surveillance during and after pregnancy are essential to improve
      pregnancy outcome. The aim of this review article is to update on the medical
      care of pregnancy in these women to ensure the best maternal and fetal prognosis.

PMID- 29224681
TI  - Role of interferons in SLE.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease
      that affects many different organ systems, with excessive production of type I
      interferons (IFNs) and autoantibodies against nucleic acids as hallmarks.
      Activation of the type I IFN system in SLE is due to continuous stimulation of
      plasmacytoid dendritic cells by endogenous nucleic acids, leading to sustained
      type I IFN production. This is reflected by an overexpression of type I IFN
      regulated genes or an IFN signature. Type I IFNs have effects on both the innate
      and adaptive immune systems, which contribute to both loss of tolerance and the
      autoimmune disease process. In this review, we discuss the current understanding
      of IFNs in SLE, focusing on their regulation, the influence of genetic
      background, and environmental factors and therapies that are under development
      aiming to inhibit the type I IFN system in SLE.

PMID- 29224682
TI  - Calcineurin inhibitors in systemic lupus erythematosus.
AB  - The calcineurin inhibitors (CNIs) belong to a group of immunosuppressive agents
      that block T-cell activation through the suppression of the calcium/calcimodulin
      dependent phosphatase calcineurin. Agents such as cyclosporine A (CSA) and
      tacrolimus (TAC) have long been used in patients with systemic lupus
      erythematosus (SLE). TAC is preferred to CSA in SLE because of the lower
      frequency of cosmetic, hypertensive and dyslipidemic adverse effects. Recent
      randomised controlled trials have demonstrated noninferiority of TAC to
      mycophenolate mofetil (MMF) or cyclophosphamide (CYC) for induction therapy of
      lupus nephritis. Low-dose combination of TAC and MMF has also been shown to
      outperform CYC pulses in inducing remission of lupus nephritis in Chinese
      patients. TAC does not affect fertility and is relatively safe in pregnancy. In
      SLE patients who are intolerant or refractory to conventional immunosuppressives,
      or where contraindications to other immunosuppressive agents exist, TAC is an
      alternative option. However, the therapeutic window of TAC is narrow, and drug
      level monitoring is required to ensure drug exposure and minimise toxicities.
      Current evidence of TAC in lupus nephritis is limited to 6 months, and its long
      term safety as maintenance therapy of SLE is yet to be determined. Newer chemical
      analogues of CNIs, such as voclosporin, with less variable plasma concentration
      are being tested in lupus nephritis.

PMID- 29224683
TI  - Reply.

PMID- 29224684
TI  - Risk Factors for Rapid Glaucoma Disease Progression.

PMID- 29224685
TI  - Spending Money to Save Money on Patient Care-The Development of Optical Coherence
      Tomography.

PMID- 29224686
TI  - Estimating Public and Patient Savings From Basic Research-A Study of Optical
      Coherence Tomography in Managing Antiangiogenic Therapy.
AB  - PURPOSE: To compare patient and Medicare savings from the use of optical
      coherence tomography (OCT) in guiding therapy for neovascular age-related macular
      degeneration (nvAMD) to the research investments made in developing OCT by the
      National Institutes of Health (NIH) and the National Science Foundation (NSF).
      DESIGN: Observational cohort study. METHODS: Main outcome measures were spending
      by Medicare as tracked by Current Procedural Terminology codes on intravitreal
      injections (67028), retinal OCT imaging (92134), and anti-vascular endothelial
      growth factor (anti-VEGF) treatment-specific J-codes (J0178, J2778, J9035, J3490,
      and J3590). These claims were identified from the Medicare Provider Utilization
      and Payment Data from the Centers for Medicare and Medicaid Services among fee
      for-service (FFS) Medicare beneficiaries from 2012 to 2015; 2008 claims were
      acquired from the 100% FFS Part B Medicare Claims File. OCT research costs were
      determined by searching for grants awarded by NIH and NSF from inception to 2015.
      All costs and savings were discounted by 3% annually and adjusted for inflation
      to 2015 dollars. RESULTS: From 2008 to 2015, the United States government and
      nvAMD patients have accrued an estimated savings of $9.0 billion and $2.2
      billion, respectively, from the use of OCT to guide personalized anti-VEGF
      treatment. The $9.0 billion represents a 21-fold return on government investment
      into developing the technology through NIH and NSF grants. CONCLUSIONS: Although
      an overall cost-benefit ratio of government-sponsored research is difficult to
      estimate because the benefit may be diffuse and delayed, the investment in OCT
      over 2 decades has been recouped many times over in just a few years through
      better personalized therapy.

PMID- 29224687
TI  - Reply.

PMID- 29224688
TI  - [Colorectal adenocarcinoma: Universal screening for MSI!]

PMID- 29224689
TI  - [The MSI status: An almost ideal marker!]

PMID- 29224690
TI  - Importance of musculoskeletal health and functional capacity through the life
      course.

PMID- 29224691
TI  - Musculoskeletal health conditions among older populations in urban slums in sub
      Saharan Africa.
AB  - BACKGROUND: Debate on the burden of musculoskeletal (MSK) conditions in lower and
      middle income countries is intensifying; yet, little knowledge so far exists on
      patterns and impacts of such conditions among general or older adult populations
      in sub-Saharan Africa (SSA). The objectives of this study are to examine the
      prevalence, potential predictors, and sequelae of MSK among older adults residing
      in two low resource informal urban settlements or "slums" in Nairobi Kenya.
      METHODS: Data on older adults aged 60 years and over from two unrelated cross
      sectional surveys on the older slum populations are used: a 2006/7 survey on the
      social, health, and overall well-being of older people (sample N = 831), and a
      2016 survey on realities and impacts of long-term care and social protection for
      older adults (sample n = 1026). Uni and multivariate regressions on the 2006/7
      data are employed to examine relationships of back pain and symptoms of arthritis
      with sex, age, wealth, unemployment, diagnoses of hypertension, and diabetes; and
      with indicators of subjective well-being and functional ability. Descriptive
      frequencies and chi-squared tests of association are used on 2016 data to
      identify the overall prevalence and locations of activity limiting MSK pain, and
      sex differences in these. RESULTS: Prevalence of past month back pain and past 2
      week symptoms of arthritis was 44% and 42.6%, respectively. Respective prevalence
      of past month activity limiting back pain and joint pain was 13.9% and 22.7%. A
      total of 42.6% of slum residents with a current health problem report MSK as the
      most severe problem. In multivariate regressions, female sex, unemployment, and
      diagnosis of hypertension are predictive of back pain and symptoms of arthritis.
      Both conditions are associated with raised odds of having lower quality of life,
      poorer life satisfaction, and depressive symptoms, and with mobility impairments
      and self-care difficulties. CONCLUSIONS: MSK conditions are salient, and a likely
      key cause of impaired subjective well-being and functioning among older slum
      populations in SSA. Further research on determinants and consequences of such
      conditions in older slum populations is required to inform debate on responses to
      MSK as part of efforts to reorient SSA health systems to aging and to improve
      slum health.

PMID- 29224692
TI  - The contribution of musculoskeletal disorders in multimorbidity: Implications for
      practice and policy.
AB  - People frequently live for many years with multiple chronic conditions
      (multimorbidity) that impair health outcomes and are expensive to manage.
      Multimorbidity has been shown to reduce quality of life and increase mortality.
      People with multimorbidity also rely more heavily on health and care services and
      have poorer work outcomes. Musculoskeletal disorders (MSDs) are ubiquitous in
      multimorbidity because of their high prevalence, shared risk factors, and shared
      pathogenic processes amongst other long-term conditions. Additionally, these
      conditions significantly contribute to the total impact of multimorbidity, having
      been shown to reduce quality of life, increase work disability, and increase
      treatment burden and healthcare costs. For people living with multimorbidity,
      MSDs could impair the ability to cope and maintain health and independence,
      leading to precipitous physical and social decline. Recognition, by health
      professionals, policymakers, non-profit organisations, and research funders, of
      the impact of musculoskeletal health in multimorbidity is essential when planning
      support for people living with multimorbidity.

PMID- 29224693
TI  - Musculoskeletal health and frailty.
AB  - Frailty is a consequence of advanced aging, where the frailty phenotype tries to
      capture overall decline in health. Frailty involves multiple physiological
      systems that are intrinsically inter-related and with highly complex
      interactions. Frailty is closely linked to musculoskeletal health;
      musculoskeletal functioning is a key component in quantifying frailty, while at
      the same time, frailty is associated with the most common age-related
      musculoskeletal conditions: osteoporosis, fractures, falls, osteoarthritis, and
      spinal conditions. Beyond that, frailty includes additional physical domains such
      as nutrition and energy, psychological, and social factors. Despite its
      recognized role in aging health, there is still a lack of consensus on a core set
      of variables and how to best define clinically relevant thresholds. This would be
      of utmost importance for additional use to evaluate many aspects associated with
      musculoskeletal health, progression and personalized interventions, and
      rehabilitation.

PMID- 29224694
TI  - Chronic musculoskeletal pain and its impact on older people.
AB  - Musculoskeletal conditions are the leading cause of disability worldwide and also
      have a large impact on many other aspects of older people's health such as low
      physical activity level, poor mobility, frailty, depression, cognitive
      impairment, falls and poor sleep quality. Clustering of musculoskeletal pain with
      other pain conditions is also common, and the number of pain sites is an
      important prognostic factor. While musculoskeletal pain is usually nociceptive in
      origin, older people with musculoskeletal conditions may also experience
      neuropathic pain and central pain syndromes. Musculoskeletal burden of disease is
      increasing because of rapid ageing of populations, especially in developing
      countries. Interaction of musculoskeletal pain with co-existing conditions,
      including other types of pain, needs to be studied in longitudinal studies to
      identify modifiable targets for intervention. Additionally, potential impacts of
      musculoskeletal pain and prognostic factors need to be investigated in developing
      countries where evidence is scarce.

PMID- 29224695
TI  - Fragility Fractures & Their Impact on Older People.
AB  - Osteoporotic fractures, in particular hip and vertebral, are a major health
      burden worldwide. The majority of these fractures occur in the elderly
      population, resulting in one of the most important causes of mortality and
      disability in older ages. Their cost for societies is enormous and is forecast to
      steadily increase over the coming decades globally. Low bone mineral density
      (BMD) remains a key preventable risk factor for fractures. Screening and
      treatment of individuals with high risk of fracture is cost-effective. Predictive
      tools including clinical risk factors, minimisation of falls risk and public
      authorities' support to create Fracture Liaison Services are paramount
      strategies.

PMID- 29224696
TI  - Spinal pain and its impact on older people.
AB  - The term 'spinal pain' collectively includes the cervical, thoracic and
      lumbosacral regions of the spine. The majority of older people experience spinal
      pain, and with an increasing proportion of older people, the prevalence of spinal
      conditions are expected to increase in the coming decades. Musculoskeletal
      conditions of the spine in the older patient commonly include osteoarthritis and
      spinal stenosis, and the result of these degenerative diseases includes pain,
      stiffness and a decreased ability to engage in everyday activities. More than
      just the burden of pain, spinal pain has a significant considerable impact on the
      wellbeing and independence of older people within the community. Spinal pain is
      poorly managed, and knowledge of safe and effective treatment strategies are
      lacking because of the exclusion of older people in clinical research. Spinal
      pain in older people is a global health problem; the physical and personal impact
      of spinal directly threatens efforts to support healthy ageing.

PMID- 29224697
TI  - Physiology of ageing of the musculoskeletal system.
AB  - This review aims to provide a summary of current concepts of ageing in relation
      to the musculoskeletal system, highlighting recent advances in the understanding
      of the mechanisms involved in the development of age-related changes in bone,
      skeletal muscle, chondroid and fibrous tissues. The key components of the
      musculoskeletal system and their functions are introduced together with a general
      overview of the molecular hallmarks of ageing. A brief description of the normal
      architecture of each of these tissue types is followed by a summary of
      established and developing concepts of mechanisms contributing to the age-related
      alterations in each. Extensive detailed description of these changes is beyond
      the scope of this review; instead, we aim to highlight some of the most
      significant processes and, where possible, the molecular changes underlying these
      and refer the reader to in-depth, subspecialist reviews of the individual
      components for further details.

PMID- 29224699
TI  - Measuring physical capacity and performance in older people.
AB  - We highlight the important differences between the concepts of capacity and
      performance and highlight the development of measures and their application in
      common conditions encountered in health care practice with older people. A number
      of expert consensus projects have concluded that mobility, balance, muscle
      strength and dexterity are core domains for capacity measurement in older people.
      Instruments with evidence of adequate psychometric properties for the evaluation
      of capacity in response to intervention programmes include the Short Physical
      Performance Battery, hand grip strength, mini-BEST and 9-hole pegboard test.
      Measures that can track individual change and convey information that can be used
      to inform clinical decision-making, individual prognosis or prediction of events
      require greater precision. However, few such measures are available. Performance
      measurement usually focuses on basic or instrumental (advanced) Activities of
      Daily Living performed by people in their usual environments. Finally, we discuss
      the limitations of physical performance and capacity measures and future
      developments that may enhance the use of these measures in health and clinical
      care.

PMID- 29224700
TI  - Preventing weakness and stiffness - A top priority for health and social care.
AB  - With growing evidence that sarcopenia, disability and frailty can be prevented
      with physical activity, people living with pain, stiffness and weakness due to a
      musculoskeletal condition should be offered physical activity as a preventive
      strategy. By changing beliefs and attitudes towards ageing and raising the value
      and importance of physical activity, disability can be avoided or delayed and the
      costly burden of social care lessened. The effects of ageing and the effects of
      muscle strength loss are often confused. Older people can increase their strength
      and decrease their fitness to that of an average person a decade younger by
      regular exercise by decreasing the fitness gap. For illustration, the inability
      to get up from a chair and get to the toilet on time is often trigger for social
      care. People who are homebound are especially at risk of inactivity, and we need
      to be innovative and creative with ways to get them out of their homes, engaged
      within the community and using technology to interact with them at home. We need
      a ubiquitous call to action and cultural shift throughout the health and social
      care ecosystem to bring all the elements together, providing a platform and tools
      to be more active and signpost to activity as a therapy for weakness and joint
      stiffness. Behaviour change and stratified approaches to identify complex cases,
      and one-to-one interventions are key to the success of this approach. Local
      leisure centres remain at the very heart of communities and should be wellness
      centres for our ageing populations making them the frontline of the NHS.

PMID- 29224701
TI  - Physical activity in older people - Case studies of how to make change happen.
AB  - Enhancing physical activity (PA) is recognized as a powerful intervention for the
      prevention and treatment of chronic diseases and disability in older people.
      Furthermore, there is an agreement that increased PA in daily life is a key
      determinant of active and healthy ageing and should be recommended for frail and
      sedentary older people. Unfortunately, relatively few older people engage in
      regular PA or stay active in the long term. This article summarizes and discusses
      PA recommendations for older adults without focussing on specific diseases,
      presents the main barriers and facilitators for increasing PA levels, and
      considers the implementation of these recommendations on the basis of the
      existing evidence. Finally, we provide case studies of PA programmes for older
      people that were successfully implemented and highlight the current lessons
      learned.

PMID- 29224698
TI  - Sarcopenia.
AB  - Sarcopenia is a condition that is characterized by loss of muscle mass, muscle
      strength and muscle functional impairment with ageing. The definition of
      sarcopenia has been through various permutations; however, an enormous recent
      breakthrough is the inclusion of the condition in the ICD-10 classification of
      diseases. This chapter covers the background issues regarding definition before
      describing the epidemiology of the disease according to human and environmental
      factors. It then provides a practical guide for the assessment of sarcopenia in a
      clinical setting and finishes with advice on present treatment and the exciting
      frontiers of future therapies.

PMID- 29224702
TI  - Early intervention to restore function and maintain healthy trajectory.
AB  - The health of the global population has undergone rapid transformation. Life
      expectancy and chronic conditions are increasing, and persons aged 65 years or
      older have become the fastest growing segment of population. The worldwide
      picture of disease burden is increasingly defined by disability instead of
      premature mortality. Population growth, ageing and sedentary lifestyles,
      particularly in developing countries, will result in a crisis for the population
      health that requires a multi-system response. The growing awareness of the
      diseases burden increases the need for accurate measurement and assessment of the
      burden and measurement of the impact of any public health action. Musculoskeletal
      (MSK) diseases are increasingly recognised as a major and important group of
      diseases, which requires more attention from society and health care systems. The
      epidemiological evidence confirms the dramatic increase in the majority of MSK
      disorders with age, a phenomenon that is occurring in all parts of the world,
      particularly among females. There is a necessity to ensure global health policies
      to recognise the importance of disability burden for overall health, well-being
      and economic prosperity for the individual and society. It is important to
      promote a common goal between public health, primary care, specialised health and
      social services to reduce disability; to encourage health programs or models of
      care addressing chronic conditions, including the importance of primary and
      secondary prevention, early intervention, care coordination, access to a
      multidisciplinary team to address the bio-psychosocial aspects of chronic
      conditions. There is an identified need to develop a Health Care Systems response
      to enable the implementation of early intervention as an effective strategy to
      reduce the burden of MSK disorders with particular importance and potential gains
      for the target population of older people who have shown an acute loss of
      function due to MSK diseases. It will contribute to meeting the 'triple aim'
      goals in health systems of improving patient's care experience (satisfaction,
      confidence and trust), improving the health of people and populations (mortality,
      disability and quality of life) and improving the societal costs of diseases.

PMID- 29224703
TI  - [Plague: A regular reemergence but not a past scourge].

PMID- 29224704
TI  - [How to improve endometriosis management].

PMID- 29224705
TI  - ?

PMID- 29224706
TI  - Prophylactic placement of permanent synthetic mesh at the time of ostomy closure
      prevents formation of incisional hernias.
AB  - BACKGROUND: Reversal of an enterostomy results in a high rate of incisional
      hernia at the ostomy site. Prophylactic mesh reinforcement of the fascial defect
      is typically not considered due to the contaminated nature of the case. We
      present the outcomes of a series of prophylactic mesh reinforcements with
      retromuscular, large-pore polypropylene at the time of enterostomy reversal.
      METHODS: Retrospective review of all ostomy reversals was performed. All cases
      with placement of synthetic mesh reinforcement were identified from a
      prospectively maintained, hernia database. Primary end points were surgical site
      occurrence, surgical site infection, and hernia occurrence. RESULTS: Ostomy
      reversal was performed in 359 patients; 91 were reinforced with mesh and 268
      without mesh. Colostomy reversal was performed in 56.5% and ileostomy in 43.5%.
      The mesh group had a greater body mass index and a greater incidence of chronic
      obstructive pulmonary disease, but groups were otherwise similar. A midline
      incisional hernia was present in 45% of the mesh group vs 4.5% in the controls.
      Incidence of surgical site occurrence and surgical site infection were similar
      for mesh and control groups (21 vs 22.8%; P = .82 and 20 vs 19.8%; P = 1.000,
      respectively). Superficial surgical site infection was less with mesh (8 vs
      16.4%; P = .039). Incidence of a hernia developing at the stoma site was
      decreased markedly with mesh (1% vs 17.2%; P < .001), as was the occurrence of a
      midline hernia (6% vs 19%; P = .004). Mesh was placed across the midline
      prophylactically in 29.7% of cases, which decreased midline hernia formation from
      24.1% to 4% (P = .019). CONCLUSION: Retromuscular placement of permanent
      synthetic mesh at the time of enterostomy reversal is effective in preventing
      development of incisional hernia without increased risk of surgical site
      occurrence or surgical site infection.

PMID- 29224707
TI  - Wide variation in cost of surgical care for parathyroidectomy: is there a need
      for standardization of practice?
AB  - BACKGROUND: Identifying hospital and provider variation in surgical cost is a
      potent method for controlling rising healthcare expenditure and delivering cost
      effective care. The purpose of this study was to examine the variation of
      hospital cost by providers for parathyroidectomy in a single academic
      institution. METHODS: We retrospectively evaluated 894 consecutive
      parathyroidectomies under 8 surgeons in our institution between September 2011
      and July 2016. Total duration of stay and cost were evaluated using nonparametric
      tests. Categorical variables were evaluated with chi2. RESULTS: The median total
      hospital cost for parathyroidectomy was $4,863.28 (interquartile range: 4,196
      5,764), but the median costs per provider varied widely from $4,522.30 to
      $12,072.87. The median duration of stay was 0 days (IQR: 0-1) and demonstrated a
      wide variation among providers. Longer duration of practice was associated with
      lower cost. Despite the variation, only 2% was readmitted after discharge with no
      patient mortality. CONCLUSION: We found substantial variation in hospital cost
      among providers for parathyroidectomy despite practicing in the same academic
      institution, with some surgeons spending 4 time more for the same operation.
      Implementing institutional standards of practice could be a method to decrease
      variation and costs of surgical care.

PMID- 29224708
TI  - The effects of hearing loss on person-centred care in residential aged care: a
      narrative review.
AB  - Person-centred care is achieved through strategies such as effective
      communication and shared decision-making. Hearing loss can lead to communication
      breakdown and social isolation in residential aged care. The review aimed to
      address how hearing loss affects person-centred care in residential aged care
      settings. Empirical literature was identified through a systematic search of
      academic databases. Articles were reviewed against an inclusion criteria and
      general inductive analysis was employed to identify recurring factors across
      included studies. Six common factors emerged from the data: communication
      breakdown, the overlap between hearing loss and cognitive impairment, social
      isolation and reduced social participation, limited access to hearing services,
      inadequate training provided to care staff, and strategies to improve
      communication. Recommended strategies to facilitate person-centred care for
      residents with hearing loss are presented. Further investigation is needed to
      understand the effects of hearing loss on residents' autonomy and shared decision
      making.

PMID- 29224709
TI  - Prevalence and Prognostic Significance of Nonsustained Ventricular Tachycardia in
      Patients With a Left Ventricular Ejection Fraction from 35% to 50.
AB  - The risk of life-threatening ventricular arrhythmias in patients with mild-to
      moderately reduced left ventricular ejection fraction (LVEF) is unknown. This
      retrospective case-control study aims to identify the prevalence, risk factors,
      and outcomes associated with the development of nonsustained ventricular
      tachycardia (NSVT) as documented on permanent pacemakers or implantable loop
      recorders in tertiary care center patients with an LVEF of 35% to 50%. Data
      pertaining to patient demographics, previous medical history, heart failure
      functional class, echocardiographic parameters, and survival were compared
      between the groups. Of the 326 patients with an LVEF within the target range, 90
      patients (27.6%) had NSVT recorded on their device and 236 patients (72.4%) did
      not. Compared with patients without NSVT, patients with NSVT had a higher body
      mass index (28.4 kg/m2 vs 26.8 kg/m2, p = 0.02), more ischemic heart disease
      (57.8% vs 32.8%, p < 0.0001), higher left atrial volume index (45.8 ml/m2 vs 42.0
      ml/m2, p = 0.04), and lower use of antiarrhythmic medications (4.4% vs 11.9%, p =
      0.04). The presence of NSVT and the duration of NSVT had no relation to survival,
      supporting the notion that NSVT is a benign finding in patients with an LVEF of
      35% to 50%.

PMID- 29224710
TI  - SPM-1-producing Pseudomonas aeruginosa ST277 clone recovered from microbiota of
      migratory birds.
AB  - The production of Sao Paulo metallo-beta-lactamase (SPM-1) is the most common
      carbapenem resistance mechanism detected among multidrug-resistant Pseudomonas
      aeruginosa clinical isolates in Brazil. Dissemination of SPM-1-producing P.
      aeruginosa has been restricted to the nosocomial settings, with sporadic reports
      of environmental isolates due to contamination by hospital sewage. Herein, we
      described the detection and molecular characterization of SPM-1-producing P.
      aeruginosa recovered from the microbiota of migratory birds in Brazil. Three
      hundred gram-negative bacilli were recovered from cloacal and choanal swabs of
      Dendrocygna viduata during a surveillance study for detection of carbapenem
      resistant isolates. All isolates were identified by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry. Molecular typing was
      performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence
      typing. MICs were determined by agar dilution, except for polymyxin B. Antibiotic
      resistance genes were detected by polymerase chain reaction (PCR) followed by DNA
      sequencing. Transcriptional levels of oprD and efflux system encoding genes were
      also carried out by quantitative real-time PCR. Nine imipenem-resistant P.
      aeruginosa isolates were recovered with 7 of them carrying blaSPM-1. Additional
      resistance genes (rmtD-1, blaOXA-56,aacA4, and aac(6')-Ib-cr) were also detected
      in all 9 isolates. The SPM-1-producing isolates showed high MICs for all beta
      lactams, fluoroquinolones, and aminoglycosides, being susceptible only to
      polymyxin B. Interestingly, all isolates showed the same PFGE pattern and
      belonged to ST277. Overexpression of MexXY-OprM and MexAB-OprM was observed in
      those isolates that did not harbor blaSPM-1. Our results suggest that migratory
      birds might have played a role in the dissemination of SPM-1-producing P.
      aeruginosa within the Brazilian territory.

PMID- 29224711
TI  - [Risk factors associated with anesthesia emergence delirium in children
      undergoing outpatient surgery].
AB  - INTRODUCTION: Anesthesia emergence delirium is a self-limiting clinical
      phenomenon very common in children. Although pathophysiology is still uncertain,
      some factors seem to be involved, such as rapid awakening in an unknown
      environment, agitation during anesthetic induction, preoperative anxiety,
      environmental disorders, use of preanesthetic medication, use of inhalational
      anesthetics, and postoperative pain. OBJECTIVE: To determine the prevalence and
      risk factors associated with anesthesia emergence delirium in children undergoing
      outpatient surgery. METHODS: A prospective observational study was carried out
      with 100 children aged 2 to 10 years, who underwent surgery on an outpatient
      basis. The study variables were: anesthesia emergence delirium and the associated
      risk factors (preoperative anxiety, child impulsive behavior, use of pre
      anesthetic medication, traumatic induction, type of anesthesia, and postoperative
      pain). Multivariate Poisson's logistic regression was used to analyze the
      possible explanatory variables, where the prevalence ratios were estimated with
      the respective 95% confidence intervals, considering a significance level of 5%.
      RESULTS: Delirium and pain were observed in 27% and 20% of children,
      respectively. Only postoperative pain after Poisson's regression, was shown to be
      associated with anesthesia emergence delirium, with a prevalence ratio of 3.91
      (p<0.000). CONCLUSION: The present study showed 27% prevalence of anesthesia
      emergence delirium in the study population. The incidence of anesthesia emergence
      delirium was higher in children who had postoperative pain.

PMID- 29224712
TI  - Superior semicircular canal dehiscence: Diagnosis and management.
AB  - The authors provide an update on the clinical manifestations, diagnosis and
      various approaches to the treatment of superior semicircular canal dehiscence
      (SSCD). SSCD is a rare condition where the bone overlying the superior
      semicircular canal thins or dehisces causing characteristic clinical findings.
      Since this was first reported in 1998 by Minor and colleagues, there has been
      much advancement made in terms of diagnosis and treatment. Signs and symptoms
      include a wide variation of both vestibular and auditory manifestations.
      Diagnosis made solely on clinical signs is difficult due to how varied the
      presentations can be and the overlap with other otologic pathologies. High
      resolution CT temporal scans have been the standard in confirming superior
      semicircular canal dehiscence, however, MRI FIESTA scans have recently been used
      to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential
      (VEMP) testing are useful screening tools. Currently, the middle fossa approach
      is the most common and standard surgical approach to repair SSCD. The
      transmastoid, endoscopic and transcanal or endaural approaches have also been
      recently utilized. Presently, there is no consensus as to the best approach,
      material or technique for repair of SSCD. As we learn more, newer and less
      invasive approaches and techniques are being used to treat SSCD. We present a
      comprehensive review of SSCD, including clinical symptoms and presentation,
      histopathology, diagnosis, treatment strategies and outcomes of intervention.

PMID- 29224713
TI  - Veterinary Oncology Immunotherapies.
AB  - The ideal cancer immunotherapy agent should be able to discriminate between
      cancer and normal cells, be potent enough to kill small or large numbers of tumor
      cells, and be able to prevent recurrence of the tumor. Tumor immunology and
      immunotherapy are among the most exciting and rapidly expanding fields; cancer
      immunotherapy is now recognized as a pillar of treatment alongside traditional
      modalities. This article highlights approaches that seem to hold particular
      promise in human clinical trials and many that have been tested in veterinary
      medicine.

PMID- 29224714
TI  - Corrigendum to "Impact of childhood adversities on depression in early adulthood:
      A longitudinal cohort study of 478,141 individuals in Sweden" [J. Affect. Disord.
      223 (2017) 95-100].

PMID- 29224715
TI  - Ebola virus disease: Biological and diagnostic evolution from 2014 to 2017.
AB  - The Ebola virus disease outbreak observed in West Africa from March 2014 to June
      2016 has led to many fundamental and applied research works. Knowledge of this
      virus has substantially increased. Treatment of many patients in epidemic
      countries and a few imported cases in developed countries led to developing new
      diagnostic methods and to adapt laboratory organization and biosafety precautions
      to perform conventional biological analyses. Clinical and biological monitoring
      of patients infected with Ebola virus disease helped to determine severity
      criteria and bad prognosis markers. It also contributed to showing the
      possibility of viral sanctuaries in patients and the risk of transmission after
      recovery. After a summary of recent knowledge of environmental and clinical viral
      persistence, we aimed to present new diagnostic methods and other biological
      tests that led to highlighting the pathophysiological consequences of Ebola virus
      disease and its prognostic markers. We also aimed to describe our lab experience
      in the care of Ebola virus-infected patients, especially technical and logistical
      changes between 2014 and 2017.

PMID- 29224716
TI  - The role of constructed wetlands in a new circular economy, resource oriented,
      and ecosystem services paradigm.
AB  - Wastewater management is included in one of the 17 Sustainable Development Goals
      (SDGs): SDG 6 is dedicated to water and sanitation and sets out to "ensure
      availability and sustainable management of water and sanitation for all". SDG 6
      expands the Millennium Development Goals (MDGs) focus on drinking water and basic
      sanitation to now cover the entire water cycle, including the management of
      water, wastewater and ecosystem resources. A UN report in 2017 states that likely
      over 80% of the wastewater worldwide is still discharged without adequate
      treatment. In several countries the wastewater management is nowadays a norm, but
      still there are open discussions about the kind of approach to be adopted, i.e.
      centralisation vs. decentralisation. The choice of the adopted technologies is
      strictly linked to environmental performances and economical aspects; one of the
      possible causes for the still enormous amount of untreated wastewater discharged
      into the environment can be the low "willingness to pay" for this kind of service
      and therefore a great focus should be given to all the technologies that are able
      to lower the treatment costs still maintaining reliable and robust performances
      in the long term. When considering wastewater as a carrier of valuable primary
      chemicals that can be easily converted to marketable products (fertilisers, bio
      plastics, soil conditioners, biofuels, etc.), and as well as a relevant source of
      "new water" to be used for specific purposes, wastewater and runoff management
      can be highlighted as one of the most exciting challenges and occasions for a
      sustainable development in the near future. The paper aims to clarify the future
      role of CWs in circular economy, resource-oriented, and ecosystem services
      approaches, which want to respond to sanitation worldwide and the future research
      needs. We give an overview on how the conventional wastewater treatment scheme
      (what we call "waste paradigm") should move towards more sustainable water and
      biogeochemical cycles following the new resource-oriented, circular economy and
      ecosystem service views. On this basis, we review the potential application of
      CWs within this new, and needed, paradigm. Finally, a meta-analysis shows that
      the scientific community involved in CWs should put more effort in making CWs
      more suitable for these new tasks.

PMID- 29224717
TI  - Fronto-parietal organization for response times in inhibition of return: The
      FORTIOR model.
AB  - Inhibition of Return (IOR) refers to a slowing of response times (RTs) for visual
      stimuli repeated at the same spatial location, as compared to stimuli occurring
      at novel locations. The functional mechanisms and the neural bases of this
      phenomenon remain debated. Here we present FORTIOR, a model of the cortical
      control of visual IOR in the human brain. The model is based on known facts about
      the anatomical and functional organization of fronto-parietal attention networks,
      and accounts for a broad range of behavioral findings in healthy participants and
      brain-damaged patients. FORTIOR does that by combining four principles of
      asymmetry: FORTIOR accounts for spatial asymmetries in the occurrence of IOR
      after brain damage and after non-invasive transcranial magnetic stimulation on
      parietal and frontal regions. It also provides a framework to understand
      dissociations between manual and saccadic IOR, and makes testable predictions for
      future experiments to assess its validity.

PMID- 29224718
TI  - Bionic Manufacturing: Towards Cyborg Cells and Sentient Microbots.
AB  - Bio-inspired engineering applies biological design principles towards developing
      engineering solutions but is not practical as a manufacturing paradigm. We
      advocate 'bionic manufacturing', a synergistic fusion of biotic and abiotic
      components, to transition away from bio-inspiration toward bio-augmentation to
      address current limitations in bio-inspired manufacturing.

PMID- 29224719
TI  - Cyberbiosecurity: From Naive Trust to Risk Awareness.
AB  - The cyber-physical nature of biotechnology raises unprecedented security
      concerns. Computers can be compromised by encoding malware in DNA sequences, and
      biological threats can be synthesized using publicly available data. Trust within
      the biotechnology community creates vulnerabilities at the interface between
      cyberspace and biology. Awareness is a prerequisite to managing these risks.

PMID- 29224720
TI  - CTNNB1 mutations in basal cell adenoma of the salivary gland.
AB  - BACKGROUND/PURPOSE: Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC)
      are uncommon salivary gland tumors comprising proliferation of basaloid cells.
      Nuclear beta-catenin expression and mutations in its encoding gene (CTNNB1) are
      reported to be specific to BCA. PIK3CA mutations are only found in BCAC not in
      BCA. However, in previous studies the number of cases was relatively small. The
      present study analyzed 44 cases of basal cell neoplasms to identify the CTNNB1
      and PIK3CA mutation profiles in this rare salivary gland tumor. METHODS: The
      basic clinical features and detailed histological patterns of 41 BCA and three
      BCAC cases were analyzed. All basal cell neoplasms and a tissue microarray of
      adenoid cystic carcinoma (AdCC) were tested for beta-catenin
      immunohistochemistry. CTNNB1, PIK3CA, and CYLD mutations were detected by PCR and
      Sanger sequencing in each case. RESULTS: Nuclear beta-catenin expression was
      present in 97.6% of BCA and 66.7% of BCAC cases but not in AdCC cases. CTNNB1
      mutations were found in 60% of BCA but not in BCAC. None of the tested cases had
      PIK3CA mutations. CTNNB1 mutation trended to be more common in those cases having
      a predominant tubular or tubulotrabecular patterns (p = 0.059). CONCLUSION: beta
      catenin immunohistochemistry is very useful for the differential diagnosis
      between BCA/BCAC and AdCC. CTNNB1 mutations are common in BCA, especially those
      with tubular or tubulotrabecular patterns.

PMID- 29224721
TI  - Synergistic Processing of Visual Contours across Cortical Layers in V1 and V2.
AB  - Visual cortical areas are interconnected via layer-specific feedforward and
      feedback projections. Such intricate connections are thought to be essential for
      parsing complex visual images, but the synergy among different layers in
      different cortical areas remains unclear. By simultaneously mapping neuronal
      activities across cortical depths in V1 and V2 of behaving monkeys, we identified
      spatiotemporally dissociable processes for grouping contour fragments and
      segregating background components. These processes generated and amplified
      contour signals within specific layers in V1 and V2. Contour-related inter-areal
      interactions, measured as Granger causality, were also dominant between these
      cortical layers within a time window when the contour signals were rapidly
      augmented. The grouping process became much faster for isolated contour elements
      compared with visual contours embedded in a complex background. Our results
      delineate the mode whereby image components are grouped and segmented through
      synergistic inter-laminar and inter-areal processes that are dynamically adjusted
      during interpretation of sensory inputs.

PMID- 29224722
TI  - NRAP-1 Is a Presynaptically Released NMDA Receptor Auxiliary Protein that
      Modifies Synaptic Strength.
AB  - NMDA receptors (NMDARs) are a subtype of postsynaptic ionotropic glutamate
      receptors that function as molecular coincidence detectors, have critical roles
      in models of learning, and are associated with a variety of neurological and
      psychiatric disorders. To date, no auxiliary proteins that modify NMDARs have
      been identified. Here, we report the identification of NRAP-1, an auxiliary
      protein in C. elegans that modulates NMDAR function. NMDAR-mediated currents were
      eliminated in nrap-1 mutants, as was NMDA-dependent behavior. We show that
      reconstitution of NMDA-gated current in Xenopus oocytes, or C. elegans muscle
      cells, depends on NRAP-1 and that recombinant NRAP-1 can convert silent NMDARs to
      functional channels. Our data indicate that NRAP-1, secreted from presynaptic
      neurons, localizes to glutamatergic synapses, where it associates with
      postsynaptic NMDARs to modify receptor gating. Thus, our studies reveal a novel
      mechanism for synaptic regulation via pre-synaptic control of NMDAR-mediated
      synaptic transmission.

PMID- 29224723
TI  - Neural Basis of Cognitive Control over Movement Inhibition: Human fMRI and
      Primate Electrophysiology Evidence.
AB  - Executive control involves the ability to flexibly inhibit or change an action
      when it is contextually inappropriate. Using the complimentary techniques of
      human fMRI and monkey electrophysiology in a context-dependent stop signal task,
      we found a functional double dissociation between the right ventrolateral
      prefrontal cortex (rVLPFC) and the bi-lateral frontal eye field (FEF). Different
      regions of rVLPFC were associated with context-based signal meaning versus
      intention to inhibit a response, while FEF activity corresponded to success or
      failure of the response inhibition regardless of the stimulus response mapping or
      the context. These results were validated by electrophysiological recordings in
      rVLPFC and FEF from one monkey. Inhibition of a planned behavior is therefore
      likely not governed by a single brain system as had been previously proposed, but
      instead depends on two distinct neural processes involving different sub-regions
      of the rVLPFC and their interactions with other motor-related brain regions.

PMID- 29224724
TI  - Injecting Instructions into Premotor Cortex.
AB  - The premotor cortex (PM) receives inputs from parietal cortical areas
      representing processed visuospatial information, translates that information into
      programs for particular movements, and communicates those programs to the primary
      motor cortex (M1) for execution. Consistent with this general function,
      intracortical microstimulation (ICMS) in the PM of sufficient frequency,
      amplitude, and duration has been shown to evoke complex movements of the arm and
      hand that vary systematically depending on the locus of stimulation. Using
      frequencies and amplitudes too low to evoke muscle activity, however, we found
      that ICMS in the PM can provide instructions to perform specific reach, grasp,
      and manipulate movements. These instructed actions were not fixed but rather were
      learned through associations between the arbitrary stimulation locations and
      particular movements. Low-amplitude ICMS at different PM locations thus evokes
      distinguishable experiences that can become associated with specific movements
      arbitrarily, providing a novel means of injecting information into the nervous
      system.

PMID- 29224726
TI  - Decoding a Decision Process in the Neuronal Population of Dorsal Premotor Cortex.
AB  - When trained monkeys discriminate the temporal structure of two sequential
      vibrotactile stimuli, dorsal premotor cortex (DPC) showed high heterogeneity
      among its neuronal responses. Notably, DPC neurons coded stimulus patterns as
      broader categories and signaled them during working memory, comparison, and
      postponed decision periods. Here, we show that such population activity can be
      condensed into two major coding components: one that persistently represented in
      working memory both the first stimulus identity and the postponed informed choice
      and another that transiently coded the initial sensory information and the result
      of the comparison between the two stimuli. Additionally, we identified relevant
      signals that coded the timing of task events. These temporal and task-parameter
      readouts were shown to be strongly linked to the monkeys' behavior when
      contrasted to those obtained in a non-demanding cognitive control task and during
      error trials. These signals, hidden in the heterogeneity, were prominently
      represented by the DPC population response.

PMID- 29224725
TI  - RORbeta Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure
      a Fluid Walking Gait.
AB  - Animals depend on sensory feedback from mechanosensory afferents for the dynamic
      control of movement. This sensory feedback needs to be selectively modulated in a
      task- and context-dependent manner. Here, we show that inhibitory interneurons
      (INs) expressing the RORbeta orphan nuclear receptor gate sensory feedback to the
      spinal motor system during walking and are required for the production of a fluid
      locomotor rhythm. Genetic manipulations that abrogate inhibitory RORbeta IN
      function result in an ataxic gait characterized by exaggerated flexion movements
      and marked alterations to the step cycle. Inactivation of RORbeta in inhibitory
      neurons leads to reduced presynaptic inhibition and changes to sensory-evoked
      reflexes, arguing that the RORbeta inhibitory INs function to suppress the
      sensory transmission pathways that activate flexor motor reflexes and interfere
      with the ongoing locomotor program. VIDEO ABSTRACT.

PMID- 29224728
TI  - Social Media, Open Science, and Data Science Are Inextricably Linked.
AB  - Should scientists use social media? Why practice open science? What is data
      science? Ten years ago, these phrases hardly existed. Now they are ubiquitous.
      Here I argue that these phenomena are inextricably linked and reflect similar
      underlying social and technological transformations.

PMID- 29224727
TI  - High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of
      Cortical Input and Output in Human M1.
AB  - Layer-dependent fMRI allows measurements of information flow in cortical
      circuits, as afferent and efferent connections terminate in different cortical
      layers. However, it is unknown to what level human fMRI is specific and sensitive
      enough to reveal directional functional activity across layers. To answer this
      question, we developed acquisition and analysis methods for blood-oxygen-level
      dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used
      these to discriminate four different tasks in the human motor cortex (M1). In
      agreement with anatomical data from animal studies, we found evidence for
      somatosensory and premotor input in superficial layers of M1 and for cortico
      spinal motor output in deep layers. Laminar resting-state fMRI showed directional
      functional connectivity of M1 with somatosensory and premotor areas. Our findings
      demonstrate that CBV-fMRI can be used to investigate cortical activity in humans
      with unprecedented detail, allowing investigations of information flow between
      brain regions and outperforming conventional BOLD results that are often buried
      under vascular biases.

PMID- 29224729
TI  - Different Cognitive Complaint Profiles in Memory Clinic and Depressive Patients.
AB  - OBJECTIVE: Cognitive complaints are considered early indicators of incipient
      Alzheimer's disease (AD) but are very common in geriatric patients, especially in
      patients with major depressive disorder (MDD). The clinical assessment of
      cognitive complaints is still poorly operationalized. Recent qualitative research
      suggests that certain phenomenologic complaint themes may have some specificity
      for prodromal AD. The aim of the study was to replicate and explore their
      occurrence in a clinical setting. METHODS: In a cross-sectional, case-control
      study using a mixed-methods approach, 23 memory clinic (cognitive complainers
      [CC]) patients, 21 psychiatric inpatients with MDD, and 21 healthy control
      subjects, aged 55-86 years, were assessed at the Department of Psychiatry and
      Psychotherapy and German Center for Neurodegenerative Diseases, Bonn. A newly
      developed semistructured interview addressing 12 complaint themes was used, and
      transcribed open format responses were coded by qualitative expert rating (theme
      absent versus present) and compared between the groups. RESULTS: Seven complaint
      themes (e.g., sense of predomination, progression) were significantly more often
      endorsed by the CC group, together with a novel theme of "distractible speech."
      Complaint themes in those with depression aligned with the depressive symptoms
      and appeared to be partly different from the complaint pattern of the CC group.
      CONCLUSION: Previously established themes were found to be feasible for
      conversion into a semistructured interview. Several complaint phenotypes were
      confirmed and previous themes significantly expanded by providing first evidence
      for a qualitatively different complaint profile in MDD compared with CC. Future
      investigations may benefit from better characterizing the phenomenologic and
      qualitative characteristics of AD-related complaints.

PMID- 29224731
TI  - Highly specific real-time quantification of diverse microRNAs in human samples
      using universal primer set frame.
AB  - In this study, one group of universal primer set frame, composed by one reverse
      transcription (RT) primer frame and a pair of quantitative real-time polymerase
      chain reaction (qRT-PCR) primer frames, was elaborately screened and designed by
      homebuilt software for sensitive and specific quantification of diverse miRNAs.
      The universal primer set frame can be applied for multiplex miRNAs detection by
      simply changing the RT-X part of RT primer frame and RP-Y part of qRT-PCR reverse
      primer frame based on target sequence. The maximum similarity of RT-Y, RT-Z and
      qRT-PCR forward primer to the human genome and human transcriptome is less than
      76%, ensuring the high specificity in human sample detection. The high
      sensitivity and broad dynamic linear range of the developed approaches by using
      designed primer set frame were demonstrated on the in vitro detection of miR-21
      and miR-155, with dynamic range of 10 fM to 10 nM and detection limit of 3.74 *
      10-15 M and 5.81 * 10-15 M for miR-21 and miR-155, respectively. In particular,
      the developed assays also have high sequence specificity which could clearly
      discriminate a single base difference in miRNA sequence. The contents of miR-21
      and miR-155 in tissue and serum samples have been successfully detected using the
      developed assays. Results indicated that miR-21 and miR-155 were elevated in
      cancer tissue and serum specimens than that of normal samples, implying the
      developed assays hold a great promise for further application in biomedical
      research and early clinical diagnosis. More importantly, the primer set frame can
      be universally used in any miRNA investigation.

PMID- 29224730
TI  - A validated calculator to estimate risk of cesarean after an induction of labor
      with an unfavorable cervix.
AB  - BACKGROUND: Induction of labor occurs in >20% of pregnancies, which equates to
      approximately 1 million women undergoing an induction in the United States
      annually. Regardless of how common inductions are, our ability to predict
      induction success is limited. Although multiple risk factors for a failed
      induction have been identified, risk factors alone are not enough to quantify an
      actual risk of cesarean for an individual woman undergoing a cesarean. OBJECTIVE:
      The objective of this study was to derive and validate a prediction model for
      cesarean after induction with an unfavorable cervix and to create a Web-based
      calculator to assist in patient counseling. STUDY DESIGN: Derivation and
      validation of a prediction model for cesarean delivery after induction was
      performed as part of a planned secondary analysis of a large randomized trial. A
      predictive model for cesarean delivery was derived using multivariable logistic
      regression from a large randomized trial on induction methods (n = 491) that took
      place from 2013 through 2015 at an academic institution. Full-term (>=37 weeks)
      women carrying a singleton gestation with intact membranes and an unfavorable
      cervix (Bishop score <=6 and dilation <=2 cm) undergoing an induction were
      included in this trial. Both nulliparous and multiparous women were included.
      Women with a prior cesarean were excluded. Refinement of the prediction model was
      performed using an observational cohort of women from the same institution who
      underwent an induction (n = 364) during the trial period. An external validation
      was performed utilizing a publicly available database (Consortium for Safe Labor)
      that includes information for >200,000 deliveries from 19 hospitals across the
      United States from 2002 through 2008. After applying the same inclusion and
      exclusion criteria utilized in the derivation cohort, a total of 8466 women
      remained for analysis. The discriminative power of each model was assessed using
      a bootstrap, bias-corrected area under the curve. RESULTS: The cesarean delivery
      rates in the derivation and external validation groups were: 27.7% (n = 136/491)
      and 26.4% (n = 2235/8466). In multivariable modeling, nulliparity, gestation age
      >=40 weeks, body mass index at delivery, modified Bishop score, and height were
      significantly associated with cesarean. A nomogram and calculator were created
      and found to have an area under the curve in the external validation cohort of
      0.73 (95% confidence interval, 0.72-0.74). CONCLUSION: A nomogram and user
      friendly Web-based calculator that incorporates 5 variables known at the start of
      induction has been developed and validated. It can be found at:
      http://www.uphs.upenn.edu/obgyn/labor-induction-calculator/. This calculator can
      be used to augment patient counseling for women undergoing an induction with an
      unfavorable cervix.

PMID- 29224732
TI  - Handheld isothermal amplification and electrochemical detection of DNA in
      resource-limited settings.
AB  - This paper demonstrates a new method for electrochemical detection of specific
      sequences of DNA present in trace amounts in serum or blood. This method is
      designed for use at the point-of-care (particularly in resource-limited
      settings). By combining recombinase polymerase amplification (RPA)- an isothermal
      alternative to the polymerase chain reaction - with an electroactive mediator,
      this electrochemical methodology enables accurate detection of DNA in the field
      using a low-cost, portable electrochemical analyzer (specifically designed for
      this type of analysis). This handheld device has four attributes: (1) It uses
      disposable, paper-based strips that incorporate screen-printed carbon electrodes;
      (2) It accomplishes thermoregulation with +/-0.1  degrees C temperature accuracy;
      (3) It enables electrochemical detection using a variety of pulse sequences,
      including square-wave and cyclic voltammetry, and coulometry; (4) It is
      operationally simple to use. Detection of genomic DNA from Mycobacterium
      smegmatis (a surrogate for M. tuberculosis-the main cause of tuberculosis), and
      from M. tuberculosis itself down to ~0.040 ng/MUL provides a proof-of-concept for
      the applicability of this method of screening for disease using molecular
      diagnostics. With minor modifications to the reagents, this method will also
      enable field monitoring of food and water quality.

PMID- 29224733
TI  - Validated MALDI-TOF-MS method for anthrax lethal factor provides early diagnosis
      and evaluation of therapeutics.
AB  - Anthrax lethal factor (LF) is a zinc-dependent endoprotease and a critical
      virulence factor for Bacillus anthracis, the causative agent of anthrax. The mass
      spectrometry (MS) method for total-LF quantification includes three steps; 1) LF
      specific antibody capture/concentration, 2) LF-specific hydrolysis of a peptide
      substrate, and 3) detection and quantification of LF-cleaved peptides by isotope
      dilution MALDI-TOF/MS. Recombinant LF spiked plasma was used for calibration and
      quality control (QC) materials. Specificity was 100% from analysis of serum and
      plasma from 383 non-infected humans, 31 rabbits, and 24 rhesus macaques.
      Sensitivity was 100% from 32 human clinical anthrax cases including infections by
      inhalation, ingestion, cutaneous and injection exposures and experimental
      infections for 29 rabbits and 24 rhesus macaques with inhalation anthrax.
      Robustness evaluation included sample storage, serum and plasma, antimicrobial
      and antitoxin effects and long-term performance. Data from 100 independent runs
      gave detection limits 0.01 ng/mL (111 amol/mL) for the 4-h method and 0.0027
      ng/mL (30 amol/mL) for an alternate 20-h method. QC precision ranged from 7.7 to
      14.8% coefficient of variation and accuracy from 0.2 to 9.8% error. The validated
      LF MS method provides sensitive quantification of anthrax total-LF using a robust
      high throughput platform for early diagnosis and evaluation of therapeutics
      during an anthrax emergency.

PMID- 29224734
TI  - Optimization of the quenching and extraction procedures for a metabolomic
      analysis of Lactobacillus plantarum.
AB  - This study evaluated the quenching and extraction procedures using different
      solvents at different temperatures for Lactobacillus plantarum ZS2058. Eight
      quenching methods that used readily available organic solvents (methanol and
      ethanol) or cryoprotectants (glycerol and dimethyl sulfoxide) were evaluated
      quantitatively, and their effects on cell membrane integrity and metabolic
      inactivation were assessed by propidium iodide and energy charge assays,
      respectively. The combination of 20% methanol and 0.9% sodium chloride (-4 
      degrees C), with the lowest propidium iodide labelling rate of 3.06 +/- 0.16% and
      the highest energy charge value of 0.849 +/- 0.003, outperformed most of its
      counterparts and was adopted for further use. To retrieve most of the cellular
      metabolites, four extraction solvent systems, including methyl tert-butyl
      ether/methanol/water, methanol/water, acetonitrile/water and
      acetonitrile/methnol/water, were evaluated. And acetonitrile/methnol/water was
      found to be the most efficient one as, among other solvents, it yielded the
      highest metabolite abundances for most of the metabolites. Furthermore, the
      protocol was subjected to analytical validation using a series of selected
      representative metabolites and yielded a linear range of 0.00128-100 MUg mL-1
      with coefficients of 0.9953-0.9999 and recovery levels of 90%-110%. These results
      suggest the reliability of the proposed method for L. plantarum ZS2058.

PMID- 29224735
TI  - A novel three-dimensional cell culture method enhances antiviral drug screening
      in primary human cells.
AB  - Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR)
      and FDA approved for treatment of non-small cell lung cancer. In a previous study
      we could show the in vitro efficacy of gefitinib for treatment of poxvirus
      infections in monolayer (2D) cultivated cell lines. Permanent cell lines and 2D
      cultures, however, are known to be rather unphysiological; therefore it is
      difficult to predict whether determined effective concentrations or the drug
      efficacy per se are transferable to the in vivo situation. 3D cell cultures,
      which meanwhile are widely distributed across all fields of research, are a
      promising tool for more predictive in vitro investigations of antiviral
      compounds. In this study the spreading of cowpox virus and the antiviral efficacy
      of gefitinib were analyzed in primary human keratinocytes (NHEK) grown in a novel
      3D extracellular matrix-based cell culture model and compared to the respective
      monolayer culture. 3D-cultivated NHEK grew in a polarized and thus a more
      physiological manner with altered morphology and close cell-cell contact.
      Infected cultures showed a strongly elevated sensitivity towards gefitinib. EGFR
      phosphorylation, cell proliferation, and virus replication were significantly
      reduced in 3D cultures at gefitinib concentrations which were at least 100-fold
      lower than those in monolayer cultures and well below the level of cytotoxicity.
      Our newly established 3D cell culture model with primary human cells is an easy
      to-handle alternative to conventional monolayer cell cultures and previously
      described more complex 3D cell culture systems. It can easily be adapted to other
      cell types and a broad spectrum of viruses for antiviral drug screening and many
      other aspects of virus research under more in vivo-like conditions. In
      consequence, it may contribute to a more targeted realization of necessary in
      vivo experiments.

PMID- 29224736
TI  - A natural small molecule inhibitor corilagin blocks HCV replication and modulates
      oxidative stress to reduce liver damage.
AB  - Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads
      to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of
      the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against
      viral hepatitis. Here, we report identification of a principal bioactive
      component 'corilagin', which showed significant inhibition of the HCV key
      enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound
      could effectively inhibit viral replication in the infectious cell culture
      system, displayed strong antioxidant activity by blocking HCV induced generation
      of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-beta mRNA
      levels. Oral administration of corilagin in BALB/c mice demonstrated its better
      tolerability and systemic bioavailability. More importantly, corilagin could
      restrict serum HCV RNA levels, decrease collagen deposition and hepatic cell
      denaturation in HCV infected chimeric mice harbouring human hepatocytes. Taken
      together, results provide a basis towards developing a pure natural drug as an
      alternate therapeutic strategy for restricting viral replication and prevent
      liver damage towards better management of HCV induced pathogenesis.

PMID- 29224737
TI  - Staging Computed Tomography in Patients With Noncurative Laparotomy for
      Periampullary Cancer: Does Nonstructured Reporting Adequately Communicate
      Resectability?

PMID- 29224738
TI  - Uncertainty about the intensity of impending pain increases ensuing pain
      responses in congenital blindness.
AB  - We have shown that congenitally blind individuals are more sensitive to painful
      heat compared to their sighted counterparts. This hypersensitivity might be at
      least partly mediated by psychological and cognitive factors, such as pain
      expectation and anxiety. Here we investigate whether uncertainty about the
      intensity of a pending painful stimulus affects pain differently in congenitally
      blind and sighted control subjects. We measured pain and anxiety in a group of 11
      congenitally blind and 11 age- and sex-matched normal sighted control
      participants. Painful stimuli were delivered under two psychological conditions,
      whereby participants were either certain or uncertain about the intensity of a
      pending noxious stimuli. Although both blind and sighted participants had
      increased anxiety ratings in the uncertain condition, pain ratings increased only
      in the congenitally blind participants. Our data therefore indicate that
      increased anxiety levels have a stronger influence on the perceived pain
      intensity in blind individuals, possibly because they allocate greater attention
      to signals of external threat.

PMID- 29224739
TI  - The Frequency of Unnecessary Testing in Hospitalized Patients.

PMID- 29224740
TI  - Chest Pain and Mental Stress-Induced Myocardial Ischemia: Sex Differences.
AB  - BACKGROUND: Mental stress-induced myocardial ischemia is a frequent phenomenon in
      patients with coronary artery disease. Women with coronary artery disease tend to
      have more mental stress-induced myocardial ischemia and more chest pain/anginal
      symptoms than men, but whether the association between mental stress-induced
      myocardial ischemia and angina burden differs in women and men is unknown.
      METHODS: This was a cross-sectional study with experimental manipulation of 950
      individuals with stable coronary artery disease. Chest pain/angina frequency in
      the previous 4 weeks was assessed with the Seattle Angina Questionnaire's angina
      frequency subscale. Mental stress-induced myocardial ischemia was assessed with
      myocardial perfusion imaging during mental stress (standardized public speaking
      task). Presence of mental stress-induced myocardial ischemia was based on expert
      readers and established criteria. A conventional (exercise or pharmacologic)
      stress test was used as a control condition. RESULTS: Overall, 338 individuals
      (37%) reported angina; 112 (12%) developed mental stress-induced myocardial
      ischemia, and 256 (29%) developed conventional stress ischemia. Women who
      reported angina had almost double the probability to develop mental stress
      induced myocardial ischemia (19% vs 10%, adjusted prevalence rate ratio, 1.90;
      95% confidence interval, 1.04-3.46), whereas there was no such difference in men
      (11% vs 11%, adjusted prevalence rate ratio, 1.09; 95% confidence interval, 0.66
      1.82). No association was found between angina symptoms and conventional stress
      ischemia for women or men. Results for ischemia as a continuous variable were
      similar. CONCLUSIONS: In women, but not in men, anginal symptoms may be a marker
      of vulnerability toward ischemia induced by psychologic stress. These results
      highlight the psychosocial origins of angina in women and may have important
      implications for the management and prognosis of women with angina.

PMID- 29224741
TI  - Identification of d-seco modified steroid derivatives with affinity for estrogen
      receptor alpha and beta isoforms using a non-transcriptional fluorescent cell
      assay in yeast.
AB  - Synthesis and biological evaluation of steroidal derivatives with anticancer
      properties is an active area of drug discovery. Here we measured the relative
      affinities of d-seco modified steroidal derivatives for estrogen receptor alpha,
      estrogen receptor beta or androgen receptor ligand binding domains using an
      optimized non-transcriptional fluorescent cell assay in yeast. Ligand binding
      domains of steroid receptors were expressed in-frame with yellow fluorescent
      protein in the yeast Saccharomyces cerevisiae. Addition of known steroid ligands
      to yeast expressing the appropriate cognate receptor results in increased
      fluorescence intensity, enabling estimation of receptor binding affinities in a
      dose-response and time-dependent manner. Relative binding affinities of d-seco
      modified steroidal derivatives 1-4 were then evaluated using this yeast system by
      live cell fluorimetry and fluorescence microscopy, coupled with in vitro
      cytotoxicity and in silico molecular docking studies. d-Seco estratriene
      derivative 2displayed strong affinity for both estrogen receptor alpha and beta
      ligand binding domains and negligible affinity for the androgen receptor ligand
      binding domain. Compound 2 also showed moderate cytotoxicity against estrogen
      receptor positive MCF-7 breast adenocarcinoma cells. In addition to
      identification of new ligands for steroid receptors, this assay could also be
      used to filter out compounds with potential for off-target interactions with
      steroid receptors during the early stages of compound screening.

PMID- 29224742
TI  - The importance of synovial inflammation in osteoarthritis: current evidence from
      imaging assessments and clinical trials.
AB  - Synovial abnormalities have been observed at multiple stages of osteoarthritis
      (OA). Increasing evidence suggests that it may play an important role in the OA
      pathological process. Many assessment systems using magnetic resonance imaging
      (MRI) and ultrasound have been established to detect synovial inflammation in OA.
      These have been used to inform the current investigation of OA disease phenotypes
      and progression and can be utilised in the future for clinical trials developing
      potential treatments. This narrative review aims to illustrate the importance of
      synovial tissue in OA and provide an overview of imaging assessments and possible
      therapies targeting synovial abnormalities.

PMID- 29224743
TI  - Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in
      Spontaneous Intracerebral Hemorrhage Patients.
AB  - BACKGROUND AND PURPOSE: Nowadays, researchers had begun to focus on the use of
      antiplatelet and statins in patients with spontaneous intracerebral hemorrhage
      (sICH), but atherosclerosis treatment remains uncertain in these patients. We
      aimed to investigate the incidence and characteristics of intracranial and
      extracranial atherosclerotic stenosis in these patients and analyze its related
      risk factors. METHODS: Intracranial and extracranial arteries of consecutive
      patients with sICH were studied retrospectively with computed tomography
      angiography of head and neck. The risk factors, severity, and distribution of
      atherosclerotic stenosis were examined and analyzed. RESULTS: We included 226
      patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of
      the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple
      stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had
      atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis.
      Intracranial and extracranial atherosclerosis was more likely to be found in
      patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep
      hemorrhage (P = .011). CONCLUSIONS: Atherosclerotic stenosis is common in
      patients with sICH, and is characterized by mild stenosis and the involvement of
      multiple sites. The stenosis of the vertebrobasilar system is relatively severe.
      Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.

PMID- 29224744
TI  - Low- versus Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Acute
      Ischemic Stroke: An Updated Meta-Analysis.
AB  - BACKGROUND: We performed a meta-analysis to compare the efficacy and safety
      between low- and standard-dose intravenous (IV) tissue-type plasminogen activator
      (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset.
      METHODS: We searched PubMed and EMBASE for relevant studies from inception to
      June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of
      symptom onset with comparison between low-dose and standard-dose tPA were
      included. The primary efficacy end point was favorable functional outcome
      (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end
      point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The
      secondary end points were independent functional outcome (mRS scores of 0-2) and
      mortality. RESULTS: A total of 11 studies were pooled in this meta-analysis. The
      low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus
      45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38)
      in primary efficacy outcome. The secondary efficacy outcome produced similar
      results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P= .33). There was no
      evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66
      1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92)
      at 90 days between low- and standard-dose therapy. In a subgroup analysis by
      ethnicity, there was no significant difference between patients of Asian and non
      Asian descent for any of the end points. CONCLUSIONS: This study showed that AIS
      patients receiving low-dose IV-tPA had comparably efficacy and safety to those
      receiving standard-dose IV-tPA. However, the effect is especially pronounced
      within the Asian population, which limits the generalizability of these results.

PMID- 29224745
TI  - Cranial MRI in a young child with cochlear implants after bilateral magnet
      removal.
AB  - A young bilateral cochlear implant (CI) user required magnetic resonance imaging
      (MRI) to determine the cause of hydrocephalus. The images obtained with the CIs
      in place were not diagnostically useful due to large artefacts generated by the
      CI magnets. We obtained useful images by bilaterally explanting the CI-magnets
      and replacing them with non-magnetic placeholder dummies then conducted the
      imaging. The artefact in the new images was greatly reduced and the images were
      diagnostically useful. Lastly, we explanted the dummies and reimplanted the CI
      magnets. This procedure should be useful to obtain useful images in CI users.

PMID- 29224746
TI  - Spontaneous regression of laryngeal carcinoma in 10 year old boy: A case report
      and review of literature.
AB  - Laryngeal carcinoma is a rare pathology in children, with only 92 cases reported.
      Spontaneous regression of laryngeal carcinoma is even more unique clinical event,
      so far only observed in adults. In this report we present an extraordinary case
      of a 10 year old patient with laryngeal squamous cell carcinoma that underwent
      spontaneous regression.

PMID- 29224747
TI  - Next-generation sequencing identifies three novel missense variants in ILDR1 and
      MYO6 genes in an Iranian family with hearing loss with review of the literature.
AB  - OBJECTIVES: Hearing impairment is the most common sensorineural disorder and is
      genetically heterogeneous. Identification of the pathogenic mutations underlying
      hearing impairment is difficult, since causative mutations in 127 different genes
      have so far been reported. METHODS: In this study, we performed Next-generation
      sequencing (NGS) in 2 individuals from a consanguineous family with hearing loss.
      RESULTS: Three novel mutations in known deafness genes were identified in the
      family; MYO6-p.R928C and -p.D1223N in heterozygous state and ILDR1-p.Y143C in
      homozygous state. Sanger sequencing confirmed co-segregation of the three
      mutations with deafness in the family. The identified mutation in ILDR1 gene is
      located in the immunoglobulin-type domain of the ILDR1 protein and the detected
      mutations in MY06 are located in the tail domain of the MYO6 protein. The
      mutations are predicted to be pathogenic by SIFT, PolyPhen and Mutation Taster.
      CONCLUSIONS: Our results suggest that either the homozygous ILDR1-p.Y143C
      mutation might be the pathogenic variant for ARNSHL or heterozygous MYO6-
      p.R928C, -p.D1223N might be involved in these patient's disorder due to compound
      heterozygousity. To our knowledge, this is the first ILDR1 and MYO6 mutations
      recognized in the southwest Iran. Our data expands the spectrum of mutations in
      ILDR1 and MYO6 genes.

PMID- 29224749
TI  - Supraglottoplasty for laryngomalacia: The experience from Concepcion, Chile.
AB  - OBJECTIVE: To review the clinical manifestations and outcomes of
      supraglottoplasty in patients with moderate to severe laryngomalacia at Guillermo
      Grant Benavente Hospital between January 2015 and January 2017. METHODS:
      Retrospective study of patients with laryngomalacia who underwent CO2 laser
      supraglottoplasty at a tertiary referral center. A review of medical records of
      these patients was performed. Epidemiological data along with symptoms,
      comorbidities, morphological type of laryngomalacia, synchronous airway lesions,
      surgery outcomes and satisfaction of parents after the procedure were recorded.
      Surgical success was defined as the resolution of the criteria of severity of
      laryngomalacia. RESULTS: Twenty-four patients were operated, 1 was excluded due
      to prior tracheostomy. Twenty-three patients were included, the median age at the
      time of surgery was 5.5 months. All the patients had stridor, 87% presented
      feeding difficulties, 34.8 % had cyanosis and 21.7% had failure to thrive. Six
      cases had congenital anomalies and four cases had nongenetic comorbidities.
      Fifteen patients (65.2%) had synchronous airway lesions. 17.4% had type I
      laryngomalacia and 82.6% were type 2. The postoperative average hospital stay was
      1.3 days. The average follow-up was 14 months and no complications were reported.
      The overall success rate of surgery was 95%. CONCLUSIONS: Patients with
      laryngomalacia and any symptom of severity should undergo a full airway
      evaluation, to rule out synchronous airway lesions, and supraglottoplasty if
      needed, as it has been shown to be a safe and effective technique for the
      management of these patients.

PMID- 29224748
TI  - Audiological findings in a de novo mutation of ANKRD11 gene in KBG syndrome:
      Report of a case and review of the literature.
AB  - KBG syndrome is a rare genetic disorder, due to a mutation of ANKRD11,
      characterized by specific craniofacial dysmorphism, short stature and macrodontia
      of upper central incisors, intellectual disability and skeletal anomalies. We
      report a de novo mutation of ANKRD11 gene in a 7-years old girl, affected by KBG
      syndrome with bilateral conductive hearing loss. The aim of this article was to
      review the audiological findings of this syndrome.

PMID- 29224750
TI  - Blood transfusion in children with sickle cell disease undergoing tonsillectomy.
AB  - INTRODUCTION: Tonsillectomy is the second most common surgery in children with
      sickle cell disease. These children are at an increased risk of perioperative
      complications due to vaso-occlusive events. Although controversial, preoperative
      blood transfusions are sometimes given in an effort to prevent such
      complications. The purpose of this study is to analyze trends in the use of blood
      transfusion for management of children with sickle cell disease (SCD) undergoing
      tonsillectomy in a national database. METHODS: Patients in the 1997-2012 KID with
      a primary procedure matching the ICD-9 procedure code for tonsillectomy (28.2
      28.3) and diagnosis code for SCD (282.60-282.69) were examined. Patients were
      split into groups by blood transfusion status and compared across variables
      including complication rate, length of stay (LOS), and hospital charges.
      Statistical analysis included chi-square test for trend, Mann-Whitney U test, and
      independent t-test. RESULTS: 1133 patients with SCD underwent tonsillectomy.
      There was a strong positive correlation between increasing chronologic year and
      the proportion of patients receiving blood transfusions, 47 (30.1%) in 1997 to 78
      (42.5%) in 2012 (r = 0.94, p = 0.005). During this period, there was no
      significant change in the rate of complications (r = -0.1, p = 0.87). Overall,
      patients receiving blood transfusion had a longer mean LOS (3.1 +/- 2.4 days vs.
      2.5 +/- 2.2 days, p < 0.005) and higher mean charge ($17,318 +/- 13,191 vs.
      $13,532 +/- 12,124, p < 0.005) compared to patients who did not receive blood
      transfusion. The rate of complications in the transfusion group, 18 of 352(5.1%),
      was not significantly different (p = 0.48) from the group without transfusion, 40
      of 626 (6.4%). CONCLUSIONS: From 1997 to 2012, there was a significant increase
      in the proportion of patients with SCD receiving perioperative blood transfusions
      for tonsillectomy. While the frequency of transfusion rose, those who received a
      transfusion had similar complication rates with increased charges and length of
      hospital stays compared to those who did not receive a transfusion.

PMID- 29224751
TI  - Epidemiological characteristics of pediatric epistaxis presenting to the
      emergency department.
AB  - OBJECTIVE: Investigate the epidemiological characteristics of pediatric epistaxis
      in the emergency department setting. STUDY DESIGN: Cross-sectional study using
      national databases. METHODS: Children (age <18 years) presenting with a diagnosis
      of epistaxis were extracted from the State Emergency Department Databases for New
      York, Florida, Iowa, and California for the calendar year 2010. Associated
      diagnoses, procedures, encounter characteristics, and demographic data were
      examined. RESULTS: There were 18,745 cases of pediatric epistaxis (mean age 7.54
      years, 57.4% male). Overall, 6.9% of patients underwent procedures to control
      epistaxis, of which 93.5% had simple anterior epistaxis control. The distribution
      of pediatric epistaxis was highest in spring and summer months (p < 0.001).
      Children from the lowest income quartile comprised a higher proportion of
      epistaxis presentations (38.8%, p < 0.001), yet were least likely to have an
      epistaxis control procedure performed (p < 0.001). Most patients had either
      Medicaid (43.8%) or private insurance (41.3%). Patients with Medicaid and those
      without healthcare coverage were least likely to undergo an epistaxis control
      procedure (p < 0.001). White children were more likely to undergo an epistaxis
      control procedure compared to those of minority backgrounds (p < 0.001).
      CONCLUSIONS: Most emergency department presentations of pediatric epistaxis are
      uninvolved cases that do not require procedural intervention. The
      overrepresentation of low socioeconomic status patients may suggest an
      overutilization of emergency services for minor cases of epistaxis, and perhaps a
      lack of access to primary care providers. This is the first study to evaluate
      racial and socioeconomic factors in relationship to pediatric epistaxis. Further
      investigation is needed to better elucidate these potential disparities.

PMID- 29224752
TI  - Incidence and factors associated with revision adenoidectomy: A retrospective
      study.
AB  - INTRODUCTION: Adenoidectomy is one of the most commonly performed pediatric
      operations worldwide. There are a proportion of children who require revision
      adenoidectomy. Yet there is little in the literature about the incidence,
      associated factors and etiology of adenoidal regrowth. The aim of this
      retrospective cohort study was to determine incidence and factors associated with
      revision adenoidectomy. METHODS: An extraction of all hospital morbidity records
      belonging to patients under the age of 18 years who underwent one or more
      adenoidectomy procedures (with or without tonsillectomy) between January 1, 2000
      and June 2016 at a tertiary care children's hospital was performed. Demographic,
      diagnostic, and procedural data were included in the analysis. Community
      prescribing information was examined for the number of courses of antibiotics
      prescribed to each patient prior to initial adenoidectomy. RESULTS: There were
      8260 patients under the age of 18 years who underwent primary adenoidectomy from
      2000 to 2016 at a tertiary pediatric hospital. 2.5% (n = 212) of patients
      underwent revision adenoidectomy in our cohort during the same time period. A
      higher proportion of females underwent revision adenoidectomy when compared to
      male counterparts (p = 0.007). Patients who were prescribed more than five
      courses of antibiotics prior to initial adenoidectomy were more likely to undergo
      revision adenoidectomy (p = 0.003). Patients with a diagnosis of otitis media
      with effusion were more likely to undergo revision adenoidectomy (p=<0.001). A
      diagnosis of asthma (p=<0.001), gastroesophageal reflux disease (GERD)
      (p=<0.001), and allergic rhinitis (p=<0.001) was associated with revision
      adenoidectomy. An age of over 4 years at the time of initial adenoidectomy was
      associated with revision adenoidectomy (p=<0.001). Adenoids that obstructed over
      75% of the nasal choanae were associated with revision adenoidectomy in this
      cohort (p=<0.001). CONCLUSION: This study has identified several factors
      associated with revision adenoidectomy.

PMID- 29224753
TI  - Castillo Morales Appliance Therapy in the treatment of drooling children.
AB  - OBJECTIVE: To evaluate the efficacy of Castillo Morales Appliance Therapy (CMAT)
      in reducing the severity and frequency of problematic drooling in children.
      METHODS: A de-identified extraction of all hospital morbidity records belonging
      to patients with drooling who underwent treatment with CMAT was performed between
      June 22, 2000 and April 12, 2016. Data were obtained from Starship Children's
      Hospital clinical records department. Demographic, diagnostic, and procedural
      data were included. Severity and frequency of drooling was quantified using the
      Thomas-Stonell and Greenberg classification method. RESULTS: There were fifty
      three children less than 17 years of age who were treated with CMAT for the
      indication of problematic drooling between June 22, 2000 and April 12, 2016. 72%
      (n = 38) of patients had a reduction in the severity and frequency of drooling
      with CMAT. Mean follow up was 51 months. These patients did not require further
      treatment for drooling with botulinum toxin or surgery. Within this group, 63% (n
      = 24) of patients had significant improvement in drooling as per the Thomas
      Stonell and Greenberg classification method (p = 0.024). CONCLUSIONS: Children
      who underwent CMAT for drooling were less likely to require further treatment
      with botulinum toxin or surgery. This result suggests that the use of CMAT in
      children with problematic drooling confers benefit.

PMID- 29224754
TI  - Prevalence of chronic ear disease among HIV+ children in Sub-Saharan Africa.
AB  - OBJECTIVES: To determine the prevalence of chronic ear disease in HIV+, highly
      active anti-retroviral therapy (HAART)-treated children and compare this to the
      prevalence in healthy children of similar age living in a similar setting.
      INTRODUCTION: From previous clinical work in Ethiopia, we suspected that chronic
      middle ear disease was common both in the general pediatric population and
      especially among children with HIV/AIDS. Few studies have examined the prevalence
      of chronic ear disease in HIV + children, particularly in those treated with
      HAART. METHODS: Full examination of the head and neck was performed by
      otolaryngologists. This including cleaning of cerumen, otoscopy and microscopic
      otoscopy when needed. Patient's medical records were reviewed. Presence or
      absence of tympanic membrane (TM) perforation (unilateral or bilateral),
      tympanosclerosis, TM atrophy, otorrhea and/or cholesteatoma was documented.
      RESULTS: 112 HIV+ and 162 healthy (HIVU) children were included. Prevalence of TM
      perforations was 17% in the HIV + infected versus 3% in the HIVU (Fisher's-Exact
      Test; OR: 7.2, 95% CI 2.5-20, p-value <0.0001). Presence of unilateral TM
      perforations was 12% in the HIV + population and 2% in the HIVU population
      (Fisher's-Exact-Test; OR: 6.8, 95% CI 2.0-22, p-value 0.002). The presence of
      bilateral perforations was 4% in the HIV + population and 1% in the HIVU
      population (Fisher's-Exact-Test; OR: 6.8, 95% CI 1.1-42, p-value 0.088). In the
      HIV + cohort, 2% were diagnosed with cholesteatoma compared to 0% in the HIVU
      population (95% CI HIV+ 0.002-0.06; HIVU 0.0-0.02) and 8% of HIV + subjects had
      active middle ear discharge, compared to 0% in the HIVU population (95% CI HIV+
      0.04-0.1; HIVU 0.0-0.02). Neither tympanosclerosis nor tympanic membrane atrophy
      was more frequent in the HIV + population compared to the HIVU population.
      Persistent or recurrent TM perforation was not more frequent in children with
      prior tympanoplasty in the HIV + population compared to the HIVU population.
      CONCLUSION: TM perforations are significantly more common in HAART-treated HIV +
      children than in healthy, age-matched HIVU population. Otorrhea and cholesteatoma
      were found only in the HIV + cohort.

PMID- 29224755
TI  - Factors associated with 30-day all-cause hospital readmission after tracheotomy
      in pediatric patients.
AB  - OBJECTIVE: To determine factors associated with post-tracheotomy hospital
      readmission within 30 days of discharge. METHODS: Children 18 years and younger
      who underwent tracheotomy at Children's Hospital Los Angeles (CHLA) between
      1/1/2005 and 12/31/2013 with at least 30 days of follow-up at CHLA were
      identified through ICD-9 procedure codes. Patient characteristics and covariates
      were obtained by linking manual chart review and administrative data. We used
      multivariate logistic regression to identify the independent association between
      risk factors and the primary outcome of 30-day all-cause same-hospital
      readmission. RESULTS: Of the 273 patients included, the median age at admission
      was 6 months [interquartile range (IQR): 1-51 months]. Among this primarily male
      (60.8%) and Hispanic (66.3%) cohort with a high proportion of discharge on
      positive pressure ventilation (47.1%), the 30-day readmission rate was 22% (n =
      60). Of the readmissions, 92% (n = 55) were unplanned and 64% (n = 35) were
      associated with acute respiratory illnesses. Multivariate regression analysis
      demonstrated that, among patients <=12 months, discharge on positive pressure
      ventilation [adjusted odds ratio (aOR) = 2.88, 95% confidence interval (CI) =
      1.19-6.97] was associated with increased odds of readmission, while gastrostomy
      tube placement during the tracheotomy hospitalization (aOR = 0.42, 95% CI = 0.19
      0.96) and prematurity (aOR = 0.35, 95% CI = 0.15-0.83) were associated with
      decreased odds of readmission. In patients >1 year of age, increased length of
      hospitalization (aOR = 1.01 per hospital day, 95% CI = 1-1.02) and presence of
      comorbid malignancy (aOR = 6.03, 95% CI = 1.25-29.16) were associated with
      increased odds of readmission. CONCLUSIONS: Over one-fifth of children undergoing
      tracheotomy had an unplanned hospital readmission within 30 days after discharge.
      Because the majority of readmissions were unplanned and due to acute respiratory
      illnesses, future research should investigate how discharge procedures and
      improved care coordination may lower readmission rates in high-risk patients
      (e.g., patients discharged on positive pressure ventilation).

PMID- 29224756
TI  - Novel PAX3 mutations causing Waardenburg syndrome type 1 in Tunisian patients.
AB  - Waardenburg syndrome (WS) is an auditory-pigmentary disease characterized by a
      clinical and genetic variability. WS is classified into four types depending on
      the presence or absence of additional symptoms: WS1, WS2, WS3 and WS4. Type 1 and
      3 are mostly caused by PAX3 mutations, while type 2 and type 4 are genetically
      heterogeneous. The aims of this study are to confirm the diagnostic of WS1 by the
      sequencing of PAX3 gene and to evaluate the genotype phenotype correlation. A
      clinical classification was established for 14 patients WS, as proposed by the
      Waardenburg Consortium, and noted a predominance of type 1 and type 2 with 6
      patients WS1, 7 patients WS2 and 1 patient WS3. A significant inter and intra
      familial clinical heterogeneity was also observed. A sequencing of PAX3 gene in
      the 6 patients WS1 confirmed the diagnosis in 4 of them by revealing three novel
      mutations that modify two functional domains of the protein: the c.942delC; the
      c.933_936dupTTAC and the c.164delTCCGCCACA. These three variations are most
      likely responsible for the phenotype, however their pathogenic effects need to be
      confirmed by functional studies. The MLPA analysis of the 2 patients who were
      sequence negative for PAX3 gene revealed, in one of them, a heterozygous deletion
      of exons 5 to 9 confirming the WS1 diagnosis. Both clinical and molecular
      approaches led to the conclusion that there is a lack of genotype-phenotype
      correlation in WS1, an element that must be taken into account in genetic
      counseling. The absence of PAX3 mutation in one patient WS1 highlights the fact
      that the clinical classification is sometimes insufficient to distinguish WS1
      from other types WS hence the interest of sequencing the other WS genes in this
      patient.

PMID- 29224757
TI  - Reproducing severe acute subglottic stenosis in a rabbit model.
AB  - OBJECTIVES: The objectives of this study were to develop an animal model with
      consistent, severe subglottic stenosis (SGS), and to develop the timeline needed
      for intervention to limit rabbit mortality. METHODS: Subglottic stenosis was
      created endoscopically using either a nylon or polypropylene brush in sixteen New
      Zealand White rabbits. The subglottic cross-sectional area was measured
      endoscopically using a right-angled probe and an open source image analysis
      software The cross-sectional areas of the stenotic and native airways were
      compared to calculate the subglottic stenosis percentage and Myer-Cotton grade
      classification. RESULTS: The average diameter of the native subglottis was 4.7 mm
      (SD 0.4). The mean subglottic stenosis percentage was 73% (SD 32) for all
      rabbits. The three rabbits injured with the nylon brush had 30, 52, and 76%
      stenosis. Nine of the 12 surviving rabbits (75%) injured with the polypropylene
      brush had a >86% subglottic stenosis. Four rabbits in the polypropylene brush
      cohort died from procedural complications. CONCLUSION: This study demonstrates a
      reliable model using a polypropylene brush to create severe acute subglottic
      stenosis. Cartilage exposure after creating the injury was associated with more
      severe stenosis. Mortality rate may have been reduced if endoscopic balloon
      dilation was performed electively seven days after injury, rather than emergently
      nine days after injury. LEVEL OF EVIDENCE: 4.

PMID- 29224758
TI  - Pediatric tinnitus: Incidence of imaging anomalies and the impact of hearing
      loss.
AB  - OBJECTIVE: Guidelines exist for evaluation and management of tinnitus in adults;
      however lack of evidence in children limits applicability of these guidelines to
      pediatric patients. Objective of this study is to determine the incidence of
      inner ear anomalies detected on imaging studies within the pediatric population
      with tinnitus and evaluate if presence of hearing loss increases the rate of
      detection of anomalies in comparison to normal hearing patients. METHODS:
      Retrospective review of all children with diagnosis of tinnitus from 2010 to 2015
      ;at a tertiary care academic center. RESULTS: 102 pediatric patients with
      tinnitus were identified. Overall, 53 patients had imaging studies with 6
      abnormal findings (11.3%). 51/102 patients had hearing loss of which 33 had
      imaging studies demonstrating 6 inner ear anomalies detected. This is an
      incidence of 18.2% for inner ear anomalies identified in patients with hearing
      loss (95% confidence interval (CI) of 7.0-35.5%). 4 of these 6 inner ear
      anomalies detected were vestibular aqueduct abnormalities. The other two
      anomalies were cochlear hypoplasia and bilateral semicircular canal dysmorphism.
      51 patients had no hearing loss and of these patients, 20 had imaging studies
      with no inner ear abnormalities detected. There was no statistical difference in
      incidence of abnormal imaging findings in patients with and without hearing loss
      (Fisher's exact test, p ;= ;0.072.) CONCLUSION: There is a high incidence of
      anomalies detected in imaging studies done in pediatric patients with tinnitus,
      especially in the presence of hearing loss.

PMID- 29224759
TI  - Dysphagia and feeding difficulties post-pediatric ingestion injury: Perspectives
      of the primary caregiver.
AB  - PURPOSE: To explore the experiences of children with dysphagia and/or feeding
      difficulties post-chemical or button battery ingestion injury from the
      perspective of the primary caregiver. METHOD: Five primary caregivers of children
      with a history of dysphagia and/or feeding difficulties post-ingestion injury (4
      chemical, 1 button battery) completed the Children's Picky Eating Questionnaire
      (CPEQ), and participated in a semi-structured interview. Interviews explored
      experiences of caring for a child with dysphagia and/or feeding difficulties,
      impressions of services and supports, and additional impacts to the child and
      family. Content analysis was used to identify key themes. RESULT: Primary
      caregiver report and CPEQ results confirmed all children had some degree of
      persisting dysphagia and/or feeding difficulties at time of interview (mean 4.13
      years' post-injury). Interviews identified five key themes: 1) The initial trauma
      of the injury, 2) The experience of associated and ongoing medical issues, 3)
      Managing altered oral intake, 4) Experiences of services and support, and 5)
      Impacts on the child, primary caregiver, and wider family unit. All caregivers
      reported significant challenges and concerns, and potential areas of service
      improvement were highlighted. CONCLUSION: The current data highlights specific
      issues experienced by primary caregivers, and poses areas for improving primary
      caregiver and family supports. Family-centered models of care are needed to
      support the whole family unit in caring for a child with dysphagia and/or feeding
      difficulties post-ingestion injury.

PMID- 29224760
TI  - Post-tonsillectomy dietary advice and haemorrhage risk: Systematic review.
AB  - OBJECTIVES: Tonsillectomy remains one of the commonest operations performed in
      children. Post-operative diet may affect post-tonsillectomy haemorrhage rate,
      although post-operative dietary advice varies. We undertook a systematic review
      of the published literature to assess if and how different post-operative diets
      were associated with differences in PTH rates following paediatric tonsillectomy,
      to provide an evidence base to inform individual otorhinolaryngologists' practice
      and for future guideline development. METHODS: A systematic review of the
      published English literature of the PubMed, Medline and Cochrane Collaboration
      databases, using search terms used included 'post-tonsillectomy', 'diet',
      'dietary advice', 'bleeding', 'haemorrhage', 'paediatric' &'children'. RESULTS:
      Eight publications were included in the review, including 5 randomised controlled
      trials, 2 case-control studies and 1 cohort study. These involved 1039 patients
      with 545 patients following a restricted/non-additive diet after tonsillectomy
      and 494 patients following an unrestricted/additive diet. The average reported
      PTH rate of patients in the restricted diet groups was 2.3% and 0.8% in patients
      in the unrestricted diet groups, which is not statistically significant (p =
      0.12, one tailed t-test). CONCLUSION: PTH following paediatric surgery does not
      appear to be affected by different post-operative diets or regimes followed by
      patients. Clinicians should not change the advice provided regarding oral intake
      and diet following tonsillectomy surgery in children.

PMID- 29224761
TI  - Direct tracheobronchopexy via left lateral thoracotomy for severe
      tracheobronchomalacia.
AB  - An infant with pulmonary atresia/ventricular septal defect/major aortopulmonary
      collateral arteries underwent unifocalization, ventriculoseptal defect closure
      and placement of a right ventricle to pulmonary artery conduit via median
      sternotomy. Aortopexy and pulmonary arteriopexy via redo sternotomy were
      insufficient to allow weaning of continuous positive airway pressure and he
      required direct tracheobronchopexy via left lateral thoracotomy to alleviate
      posterior trachealis intrusion along the length of the trachea and left main
      bronchus. He also underwent laryngotracheoplasty with placement of a posterior
      costal cartilage graft for bilateral vocal cord paralysis. The patient was weaned
      from positive pressure and discharged in stable condition.

PMID- 29224762
TI  - Outcomes of tympanoplasty in children with down syndrome.
AB  - INTRODUCTION: The prevalence of chronic otitis media with effusion (COME), and
      Eustachian tube dysfunction (ETD) is high in Down syndrome (DS) patients. This
      often necessitates multiple tympanostomy tube (TT) placements resulting in a
      higher rate of persistent tympanic membrane (TM) perforation requiring
      tympanoplasty for repair. OBJECTIVES: To assess risk factors for persistent
      perforation and outcomes of tympanoplasty in DS patients. METHODS: Retrospective
      case series of 91 ears in 69 DS patients with TM perforations, who were either
      observed or underwent tympanoplasty. Clinical features, surgical outcomes, and
      hearing outcomes were assessed. RESULTS: 91 ears were evaluated. Sixty
      perforations were observed, and 31 perforations were repaired. The closure rate
      was 54.8% for primary surgery, and 70.9% after secondary surgical interventions
      in the Tympanoplasty Group, compared to 33.0% spontaneous closure rate in the
      Observation Group (p < 0.001). The only risk factor for failed tympanoplasty
      repair was persistent COME/ETD (OR 27.2, p = 0.001). In the Observation Group
      perforations diagnosed at an older age, with >3 TT insertions, and with
      persistent COME/ETD were less likely to close spontaneously. Patients undergoing
      tympanoplasty had worse preoperative pure tone averages than those being
      observed, but significant improvement in air-bone gaps were noted in the
      Tympanoplasty Group (p = 0.02) post-operatively. Patients were often
      rehabilitated with hearing aids regardless of intervention (53.3% Observation
      Group, 48.4% Tympanoplasty Group). CONCLUSIONS: Persistent TM perforation in
      children with Down syndrome was associated with a history of COME/ETD, and
      multiple prior TT insertions. Tympanoplasty was successful for repair in most
      patients who underwent surgical intervention, but residual hearing loss was
      common.

PMID- 29224763
TI  - Tonsillectomy or tonsillotomy? A systematic review for paediatric sleep
      disordered breathing.
AB  - BACKGROUND: Recent evidence has challenged the practice of tonsillectomy in
      children with sleep-disordered breathing. Tonsillotomy
      (subtotal/partial/intracapsular tonsillectomy) has been proposed as an
      alternative with equivalent effectiveness and decreased post-operative morbidity,
      thus improving cost-effectiveness. OBJECTIVE: To systematically review the
      literature comparing clinical efficacy, post-operative morbidity, and cost
      effectiveness of tonsillotomy and tonsillectomy in paediatric (<16yo) patients
      with sleep-disordered breathing. DATA SOURCES: A systematic search of MEDLINE,
      EMBASE, and CENTRAL (1984-July 2014) was conducted. Papers in English directly
      comparing post-operative outcomes in tonsillectomy and tonsillotomy in children
      undergoing surgery for sleep-disordered breathing were included. REVIEW METHODS:
      Two authors independently assessed abstracts for relevance, with disagreements
      resolved by a third author. Selected studies were independently assessed
      regarding inclusion and exclusion criteria. RESULTS: Thirty-two studies satisfied
      inclusion and exclusion criteria (19 randomised, 13 non-randomised). Patient
      satisfaction, quality-of-life, and polysomnographic improvement post-surgery did
      not vary between tonsillotomy and tonsillectomy. Tonsillotomy reduced the odds of
      a secondary haemorrhage by 79% (OR 0.21, 95% CI 0.17-0.27, p < 0.01), decreased
      post-operative pain and reduced return to normal oral intake by 2.8 days (95% CI
      1.08-4.52, p < 0.01). The odds of readmission were decreased by 62% (OR 0.38, 95%
      CI 0.23-0.60, p < 0.01). Tonsillotomy had a slightly higher rate of symptom
      recurrence (4.51%) than tonsillectomy (2.55%), the long-term impact of which was
      unclear. CONCLUSION: Current evidence supports tonsillotomy in children with
      obstructive surgical indications. It is likely to reduce post-operative
      haemorrhage, pain, and facilitate a faster return to normal diet and activity.
      Healthcare burden is decreased due to fewer post-operative complications and
      reduced need for medical re-contact. More research is necessary to assess the
      risk of recurrence, and further classification of secondary haemorrhage severity
      is required to fully clarify the clinical benefit of tonsillotomy.

PMID- 29224764
TI  - Recalcitrant chronic rhinosinusitis in the setting of fucosidosis, a rare
      lysosomal storage disorder.
AB  - Fucosidosis is an autosomal recessive lysosomal storage disorder caused by the
      deficiency of alpha-L-fucosidase. We present the case of an affected female in
      the second decade of life with chronic rhinosinusitis (CRS) including
      recalcitrant polypoid inflammation, which has not been previously reported in the
      literature. With the advancement of life-prolonging measures, children with
      lysosomal storage disorders may suffer increasingly from CRS due to the
      lymphohistiocytic and macrophage infiltrate of the paranasal sinus mucosa that
      resembles severe polypoid inflammation.

PMID- 29224765
TI  - Pre- and post-operative application of acoustic rhinometry in children with
      otitis media with effusion and with or without adenoid hypertrophy-a
      retrospective analysis.
AB  - BACKGROUND: There is no standardized scheme for preoperative evaluation of
      adenoid hypertrophy or a consensus on surgical indications for adenoidectomy in
      children with otitis media with effusion (OME), especially for young children
      intolerant to nasal endoscopic assessment. The aim of this study was to evaluate
      the efficacy and reliability of acoustic rhinometry (AR) in evaluating benefits
      from adenoidectomy in children with OME. METHOD: Children with OME who were
      scheduled for surgical intervention were reviewed and AR tests performed
      preoperatively and postoperatively. The patients were divided into two groups
      based on the surgical strategy (Group I: tympanostomy tube placement alone; Group
      II: tympanostomy tube placement plus adenoidectomy). Correlation and regression
      analyses were performed to assess the relationship between findings of AR and
      nasal endoscopy. AR parameters including minimal nasal cross-sectional area
      (MCA), and nasopharyngeal volume (NPV), as well as scores of subjective symptoms
      were obtained to evaluate the utility of AR pre- and post-surgery. RESULTS: Sixty
      five children aged 4-10 years who met the inclusion criteria were included. No
      significant differences in gender or age distribution were observed between Group
      I and Group II. MCA, as well as NPV significantly decreased in Group II when
      compared with Group I (p = 0.000). A significant inverse correlation was observed
      between NPV and choanal obstruction ratio in both groups I (r = -0.625, p <
      0.001) and II (r = -0.570, p < 0.001). A significant difference between
      preoperative and postoperative NPV and subjective symptom scores was observed in
      group II after adenoidectomy (p = 0.000). CONCLUSION: AR parameters showed a good
      clinical correlation with findings of nasal endoscopy and thus may be useful for
      evaluating candidacy for surgical adenoidectomy among children with OME,
      especially in whom preoperative nasal endoscopic examination is not feasible.
      Additionally, AR can reveal the changes occurring within the nasopharyngeal
      passage before and after adenoidectomy.

PMID- 29224766
TI  - Reversible profound sensorineural hearing loss due to propranolol sensitive
      hemangioma in an infant with PHACE syndrome.
AB  - PHACE syndrome is the association of large or segmental infantile hemangiomas of
      the face or scalp with abnormalities within the posterior fossa, arteries,
      cardiovascular system, and eyes. We present a case of reversible profound
      sensorineural hearing loss due to a cerebellopontine angle infantile hemangioma
      that was successfully treated with propranolol.

PMID- 29224767
TI  - Lugol's solution eradicates Staphylococcus aureus biofilm in vitro.
AB  - OBJECTIVES: The aim of the study was to evaluate the antibacterial efficacy of
      Lugol's solution, acetic acid, and boric acid against Staphylococcus aureus
      biofilm. METHODS: The efficacy of Lugol's solution 1%, 0.1%, and 0.05%, acetic
      acid 5% or boric acid 4.7% for treatment of Staphylococcus aureus biofilm in
      vitro was tested using 30 clinical strains. Susceptibility in the planktonic
      state was assessed by disk diffusion test. Antiseptic effect on bacteria in
      biofilm was evaluated by using a Biofilm-oriented antiseptic test (BOAT) based on
      metabolic activity, a biofilm bactericidal test based on culturing of surviving
      bacteria and confocal laser scanning microscopy combined with LIVE/DEAD staining.
      RESULTS: In the planktonic state, all tested S. aureus strains were susceptible
      to Lugol's solution and acetic acid, while 27 out of 30 tested strains were
      susceptible to boric acid. In biofilm the metabolic activity was significantly
      reduced following exposure to Lugol's solution and 5% acetic acid, while boric
      acid exposure led to no significant changes in metabolic activities. In biofilm,
      biocidal activity was observed for Lugol's solution 1% (30/30), 0.1% (30/30), and
      0.05% (26/30). Acetic acid and boric acid showed no bactericidal activity in this
      test. Confocal laser scanning microscopy, assessed in 4/30 strains, revealed
      significantly fewer viable biofilm bacteria with Lugol's solution (1% p < 0.001,
      0.1% p = 0.001 or 0.05% p = 0.001), acetic acid 5% for 10 min (p = 0.001) or 30
      min (p = 0.015), but not for acetic acid for 1 min or boric acid. CONCLUSION:
      Lugol's solution 1.0% and 0.1% effectively eradicated S. aureus in biofilm and
      could be an alternative to conventional topical antibiotics where S. aureus
      biofilm is suspected such as external otitis, pharyngitis and wounds.

PMID- 29224768
TI  - Newborn hearing screening failure and maternal factors during pregnancy.
AB  - OBJECTIVE: Temporary conductive hearing loss due to amniotic fluid accumulation
      in the middle ear cavity may lead to failure (false positive) in newborn hearing
      screening tests. The aim of this study was to identify whether amniotic fluid
      index has association with failure of the initial newborn otoacoustic emission
      (OAE) screening test. METHODS: A cohort study in a tertiary hospital center
      (Royal Victoria Hospital, Montreal) was constructed from 70 newborns that failed
      the OAE test, but passed a subsequent auditory brainstem response (ABR) test, and
      75 randomly selected newborns that passed initial otoacoustic emission testing.
      Maternal (including the amniotic fluid index in the third trimester) and newborn
      clinical data were extracted from medical records. Statistical association models
      were built to determine variables that influenced hearing screen passage or
      failure. RESULTS: The two arms of the cohort had no significant differences in
      maternal or child clinical indices, including in amniotic fluid index. Calculated
      as individual odds ratios, maternal tobacco [95% CI of odds ratio: 0.04, 0.59, p
      = 0.0078], and drug use [95% CI of odds ratio: 0.0065, 0.72, p = 0.058]
      [borderline significance] were associated with failing the otoacoustic emission
      testing. CONCLUSIONS: Amniotic fluid index was not found to be associated with
      failure of otoacoustic emission screening in newborns. However, our study
      unveiled an interesting unexpected association of OAE failure with maternal
      smoking and/or drug use. This finding can help alleviate some of the time, cost
      and parental anxiety related to failed OAE screening. In selected cases of
      maternal smoking or drug use we might want to replace or add OAE to the ABR test
      in newborn hearing screening protocols, that don't perform both tests before
      discharge.

PMID- 29224769
TI  - Evaluation of speech reception threshold in noise in young CochlearTM Nucleus(r)
      system 6 implant recipients using two different digital remote microphone
      technologies and a speech enhancement sound processing algorithm.
AB  - OBJECTIVE: Children affected by hearing loss can experience difficulties in
      challenging and noisy environments even when deafness is corrected by Cochlear
      implant (CI) devices. These patients have a selective attention deficit in
      multiple listening conditions. At present, the most effective ways to improve the
      performance of speech recognition in noise consists of providing CI processors
      with noise reduction algorithms and of providing patients with bilateral CIs. The
      aim of this study was to compare speech performances in noise, across increasing
      noise levels, in CI recipients using two kinds of wireless remote-microphone
      radio systems that use digital radio frequency transmission: the Roger Inspiro
      accessory and the Cochlear Wireless Mini Microphone accessory. METHODS: Eleven
      Nucleus Cochlear CP910 CI young user subjects were studied. The signal/noise
      ratio, at a speech reception threshold (SRT) value of 50%, was measured in
      different conditions for each patient: with CI only, with the Roger or with the
      MiniMic accessory. The effect of the application of the SNR-noise reduction
      algorithm in each of these conditions was also assessed. The tests were performed
      with the subject positioned in front of the main speaker, at a distance of 2.5 m.
      Another two speakers were positioned at 3.50 m. The main speaker at 65 dB issued
      disyllabic words. Babble noise signal was delivered through the other speakers,
      with variable intensity. RESULTS: The use of both wireless remote microphones
      improved the SRT results. Both systems improved gain of speech performances. The
      gain was higher with the Mini Mic system (SRT = -4.76) than the Roger system (SRT
      = -3.01). The addition of the NR algorithm did not statistically further improve
      the results. CONCLUSION: There is significant improvement in speech recognition
      results with both wireless digital remote microphone accessories, in particular
      with the Mini Mic system when used with the CP910 processor. The use of a remote
      microphone accessory surpasses the benefit of application of NR algorithm.

PMID- 29224770
TI  - Pain control following tonsillectomy in children: A survey of patients.
AB  - OBJECTIVE: This prospective study aimed to survey pediatric patients and their
      parents after tonsillectomy to assess their pain management utilization and
      satisfaction. INTRODUCTION: Tonsillectomy is the second most common surgical
      procedure performed in pediatric patients. Postoperative recovery is often
      associated with high levels of pain and severe functional limitations. There is
      currently no consensus on pain control regimens. Additionally, a recent FDA Black
      Box Warning on narcotic use has caused more uncertainty in appropriate pain
      control regimens. METHODS: 111 pediatric patients (<=18 years) included in this
      study underwent tonsillectomy with or without adenoidectomy between October 2013
      and August 2015. Postoperatively, each patient/parent was counseled to alternate
      on an over-the-counter regimen of acetaminophen and ibuprofen and given an
      additional as-needed acetaminophen with hydrocodone prescription. A survey was
      administered during the patient's 2-week follow-up that included questions
      regarding pain levels, worst post-op pain day, pain medications taken during
      recovery, and patient/parental perceived satisfaction of having the acetaminophen
      with hydrocodone prescription. RESULTS: 84 patients/parents (75.7%) felt that OTC
      medications were not adequate for pain control and used hydrocodone at least
      once. Between those who took hydrocodone versus those who did not, there was no
      significant difference in mean age (6.7 +/- 2.9 vs. 6.0 +/- 2.4 years),
      percentage of patients with severe pain (36.9% vs. 22.2%) and worst post-op pain
      day (4.3 +/- 1.5 vs. 3.9 +/- 1.9 days) (p > 0.05). However, regardless of pain
      control regimen followed, the majority of patients/parents found it valuable to
      have the hydrocodone prescription (p = 0.004). CONCLUSION: Post-tonsillectomy
      patients and their parents find being provided with an acetaminophen-hydrocodone
      prescription is therapeutically valuable, and many find it necessary in their
      postoperative pain management. However, further studies are needed to determine
      patient factors that influence narcotic utilization.

PMID- 29224771
TI  - Revision repair of type IV laryngotracheoesophageal cleft using multiple long
      tapered engaging grafts.
AB  - An 8 year-old female with esophageal atresia and a type IV
      laryngotracheoesophageal cleft underwent tracheostomy, gastric pull-up and
      fundoplication with G-tube insertion at birth. She remained nil per os due to
      aspiration. The trachealis was separated from the esophagus that was
      reapproximated and clavicular periosteum was placed. A long posterior costal
      cartilage graft that engaged behind the cricoid plate and tapered inferiorly was
      inserted. A second thin cartilage graft was sutured to it distally to extend the
      length of the repair. This allowed for removal of the tracheostomy and oral
      feeding while providing a four-layer closure to prevent aspiration.

PMID- 29224772
TI  - Resolution of vocal fold immobility in preterm infants.
AB  - INTRODUCTION: Vocal fold immobility (VFI) is an important sequela of preterm
      birth due to patent ductus arteriosus (PDA) ligation and invasive ventilation. A
      minority of these patients experience VFI resolution. The purpose of this study
      is to determine factors associated with VFI resolution in preterm infants.
      METHODS: This is a case control study of preterm (<37 weeks gestation) infants
      admitted to a metropolitan Level IV neonatal intensive care unit from 2006 to
      2012. All patients diagnosed with VFI by flexible nasolaryngoscopy were divided
      into 2 cohorts: those with and without laryngoscopic resolution of VFI during
      follow-up. Univariate and multivariate analyses were performed to determine
      factors associated with VFI resolution. RESULTS: Of 71 patients with VFI and
      adequate follow-up, 17 (23.9%) experienced resolution. Median (range) follow-up
      was 25.7 (0.4-91.3) months and time to resolution 4.4 (0.4-38.8) months. Compared
      to the ongoing-VFI cohort, those who experienced resolution had higher median
      gestational age (31 vs 25 weeks, p = 0.006) and birth weight (1550 vs 765 g, p =
      0.02), and lower likelihood of undergoing PDA ligation (47.1% vs 77.8%, p =
      0.02). On multivariate analysis, history of PDA ligation remained independently
      associated with a lower likelihood of VFI resolution (p = 0.02, OR 0.2, 95% CI
      0.1-0.8). Among PDA ligation patients, birth weight >1000 g was more common in
      the resolution cohort compared to the ongoing-VFI cohort (62.5% vs 24.4%, p =
      0.047). CONCLUSION: While lower birth weight and gestational age are known risk
      factors for VFI following PDA ligation, in this study, these factors were also
      associated with a decreased likelihood of VFI resolution. Furthermore, PDA
      ligation appears to be a risk for both the development and persistence of VFI.
      This evidence should inform prognosis and intervention decisions for preterm
      infants with VFI.

PMID- 29224773
TI  - Parental knowledge and attitudes to childhood hearing loss and hearing services
      in the Solomon Islands.
AB  - OBJECTIVE: An understanding of parental knowledge and attitudes towards childhood
      hearing loss is essential to the successful implementation of audiology services.
      The present study aimed to investigate parental knowledge and attitudes among
      parents in the Solomon Islands. METHODS AND MATERIALS: A total of 100 mothers and
      50 fathers were administered a questionnaire via semi-structured interviews.
      RESULTS: Highest parental awareness of aetiology of childhood hearing loss was
      noted for otitis media (94%), noise exposure (87.3%), and family history (72.7%).
      The highest parental awareness concerning public health initiatives to
      reduce/prevent otitis media was noted for routine childhood immunizations (84%)
      and breast-feeding (76%). Higher rates of knowledge in fathers than in mothers
      included otitis media (p = 0.038), noise exposure (p = 0.007), and breast-feeding
      (p = 0.031). Approximately half of parents (56%) agreed that curses may cause
      hearing loss. Overall parental responses showed positive support for infant
      hearing screening programs (96%) and school-based ear and hearing health
      examinations (99.3%). CONCLUSIONS: High levels of parental readiness and support
      for childhood hearing services in the Solomon Islands was evident. Knowledge of
      aetiology of childhood hearing loss was highest for otitis media, noise exposure,
      and family history. Knowledge and attitudes of fathers to childhood hearing loss
      and hearing services was either the same or better than that of mothers.

PMID- 29224774
TI  - Australian children with cleft palate achieve age-appropriate speech by 5 years
      of age.
AB  - INTRODUCTION: Children with cleft palate demonstrate atypical speech sound
      development, which can influence their intelligibility, literacy and learning.
      There is limited documentation regarding how speech sound errors change over time
      in cleft palate speech and the effect that these errors have upon mono-versus
      polysyllabic word production. The objective of this study was to examine the
      phonetic and phonological speech skills of children with cleft palate at ages 3
      and 5. METHODS: A cross-sectional observational design was used. Eligible
      participants were aged 3 or 5 years with a repaired cleft palate. The Diagnostic
      Evaluation of Articulation and Phonology (DEAP) Articulation subtest and a non
      standardised list of mono- and polysyllabic words were administered once for each
      child. The Profile of Phonology (PROPH) was used to analyse each child's speech.
      RESULTS: N = 51 children with cleft palate participated in the study. Three-year
      old children with cleft palate produced significantly more speech errors than
      their typically-developing peers, but no difference was apparent at 5 years. The
      5-year-olds demonstrated greater phonetic and phonological accuracy than the 3
      year-old children. Polysyllabic words were more affected by errors than
      monosyllables in the 3-year-old group only. CONCLUSIONS: Children with cleft
      palate are prone to phonetic and phonological speech errors in their preschool
      years. Most of these speech errors approximate typically-developing children by 5
      years. At 3 years, word shape has an influence upon phonological speech accuracy.
      Speech pathology intervention is indicated to support the intelligibility of
      these children from their earliest stages of development.

PMID- 29224775
TI  - Photopigments and the dimensionality of animal color vision.
AB  - Early color-matching studies established that normal human color vision is
      trichromatic. Subsequent research revealed a causal link between trichromacy and
      the presence in the retina of three classes of cone photopigments. Over the
      years, measurements of the photopigment complements of other species have
      expanded greatly and these are frequently used to predict the dimensionality of
      an animal's color vision. This review provides an account of how the linkage
      between the number of active photopigments and the dimensions of human color
      vision developed, summarizes the various mechanisms that can impact photopigment
      spectra and number, and provides an across-species survey to examine cases where
      the photopigment link to the dimensionality of color vision has been claimed. The
      literature reveals numerous instances where the human model fails to account for
      the ways in which the visual systems of other animals exploit information
      obtained from the presence of multiple photopigments in support of their
      behavior.

PMID- 29224776
TI  - Development of a SYBR Green I real-time PCR for detection and quantitation of
      orthopoxvirus by using Ectromelia virus.
AB  - Ectromelia virus (ECTV) is the causative agent of mousepox, which has devastating
      effects in laboratory-mouse colonies and causes economic loss in biomedical
      research. More importantly, ECTV has been extensively used as an excellent model
      for studies of the pathogenesis and immunobiology of human smallpox. A rapid and
      sensitive SYBR Green I-based real-time PCR assay was developed and used for the
      detection and quantitation of orthopoxvirus by using ECTV in this study. Primers
      targeted to the highly conserved region of major core protein P4b gene of
      orthopoxvirus were designed and the standard plasmid was constructed. This assay
      was able to detect a minimum of 10 copies of standard DNA and 5 TCID50 units of
      ECTV. In addition, no cross-reactions were observed with two DNA viruses, such as
      herpes simplex virus and swine pseudorabies virus, and one RNA virus, vesicular
      stomatitis virus. Furthermore, intra- and inter-assay variability data showed
      that this method had a highly reproducibility and reliability. Moreover, the
      current assay was faster and had a higher sensitivity for detection of ECTV
      genomic DNA in cell cultured and clinical test samples. Therefore, the high
      sensitivity and reproducibility of this SYBR Green real-time PCR approach is a
      more effective method than the conventional PCR for ECTV diagnosis and
      quantitation.

PMID- 29224778
TI  - Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell.
AB  - Hematopoietic stem cell transplantation is a potential curative therapy for
      malignant and nonmalignant diseases. Improving the efficiency of stem cell
      collection and the quality of the cells acquired can broaden the donor pool and
      improve patient outcomes. We developed a rapid stem cell mobilization regimen
      utilizing a unique CXCR2 agonist, GRObeta, and the CXCR4 antagonist AMD3100. A
      single injection of both agents resulted in stem cell mobilization peaking within
      15 min that was equivalent in magnitude to a standard multi-day regimen of
      granulocyte colony-stimulating factor (G-CSF). Mechanistic studies determined
      that rapid mobilization results from synergistic signaling on neutrophils,
      resulting in enhanced MMP-9 release, and unexpectedly revealed genetic
      polymorphisms in MMP-9 that alter activity. This mobilization regimen results in
      preferential trafficking of stem cells that demonstrate a higher engraftment
      efficiency than those mobilized by G-CSF. Our studies suggest a potential new
      strategy for the rapid collection of an improved hematopoietic graft.

PMID- 29224777
TI  - YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
AB  - There is considerable evidence that chromosome structure plays important roles in
      gene control, but we have limited understanding of the proteins that contribute
      to structural interactions between gene promoters and their enhancer elements.
      Large DNA loops that encompass genes and their regulatory elements depend on CTCF
      CTCF interactions, but most enhancer-promoter interactions do not employ this
      structural protein. Here, we show that the ubiquitously expressed transcription
      factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions
      in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active
      enhancers and promoter-proximal elements and forms dimers that facilitate the
      interaction of these DNA elements. Deletion of YY1 binding sites or depletion of
      YY1 protein disrupts enhancer-promoter looping and gene expression. We propose
      that YY1-mediated enhancer-promoter interactions are a general feature of
      mammalian gene control.

PMID- 29224779
TI  - Combined Social and Spatial Coding in a Descending Projection from the Prefrontal
      Cortex.
AB  - Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL,
      part of medial prefrontal cortex) has been implicated in social behavior, it is
      not clear which neurons are relevant or how they contribute. We found that PL
      contains anatomically and molecularly distinct subpopulations that target three
      downstream regions that have been implicated in social behavior: the nucleus
      accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc
      projecting PL neurons (PL-NAc), but not the other subpopulations, decreased the
      preference for a social target. To determine what information PL-NAc neurons
      convey, we selectively recorded from them and found that individual neurons were
      active during social investigation, but only in specific spatial locations.
      Spatially specific manipulation of these neurons bidirectionally regulated the
      formation of a social-spatial association. Thus, the unexpected combination of
      social and spatial information within the PL-NAc may contribute to social
      behavior by supporting social-spatial learning.

PMID- 29224780
TI  - A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity.
AB  - Breast cancer (BC) comprises multiple distinct subtypes that differ genetically,
      pathologically, and clinically. Here, we describe a robust protocol for long-term
      culturing of human mammary epithelial organoids. Using this protocol, >100
      primary and metastatic BC organoid lines were generated, broadly recapitulating
      the diversity of the disease. BC organoid morphologies typically matched the
      histopathology, hormone receptor status, and HER2 status of the original tumor.
      DNA copy number variations as well as sequence changes were consistent within
      tumor-organoid pairs and largely retained even after extended passaging. BC
      organoids furthermore populated all major gene-expression-based classification
      groups and allowed in vitro drug screens that were consistent with in vivo xeno
      transplantations and patient response. This study describes a representative
      collection of well-characterized BC organoids available for cancer research and
      drug development, as well as a strategy to assess in vitro drug response in a
      personalized fashion.

PMID- 29224781
TI  - Structural Basis for Regulated Proteolysis by the alpha-Secretase ADAM10.
AB  - Cleavage of membrane-anchored proteins by ADAM (a disintegrin and
      metalloproteinase) endopeptidases plays a key role in a wide variety of
      biological signal transduction and protein turnover processes. Among ADAM family
      members, ADAM10 stands out as particularly important because it is both
      responsible for regulated proteolysis of Notch receptors and catalyzes the non
      amyloidogenic alpha-secretase cleavage of the Alzheimer's precursor protein
      (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain,
      which, together with biochemical and cellular studies, reveals how access to the
      enzyme active site is regulated. The enzyme adopts an unanticipated architecture
      in which the C-terminal cysteine-rich domain partially occludes the enzyme active
      site, preventing unfettered substrate access. Binding of a modulatory antibody to
      the cysteine-rich domain liberates the catalytic domain from autoinhibition,
      enhancing enzymatic activity toward a peptide substrate. Together, these studies
      reveal a mechanism for regulation of ADAM activity and offer a roadmap for its
      modulation.

PMID- 29224782
TI  - Mfd Dynamically Regulates Transcription via a Release and Catch-Up Mechanism.
AB  - The bacterial Mfd ATPase is increasingly recognized as a general transcription
      factor that participates in the resolution of transcription conflicts with other
      processes/roadblocks. This function stems from Mfd's ability to preferentially
      act on stalled RNA polymerases (RNAPs). However, the mechanism underlying this
      preference and the subsequent coordination between Mfd and RNAP have remained
      elusive. Here, using a novel real-time translocase assay, we unexpectedly
      discovered that Mfd translocates autonomously on DNA. The speed and processivity
      of Mfd dictate a "release and catch-up" mechanism to efficiently patrol DNA for
      frequently stalled RNAPs. Furthermore, we showed that Mfd prevents RNAP
      backtracking or rescues a severely backtracked RNAP, allowing RNAP to overcome
      stronger obstacles. However, if an obstacle's resistance is excessive, Mfd
      dissociates the RNAP, clearing the DNA for other processes. These findings
      demonstrate a remarkably delicate coordination between Mfd and RNAP, allowing
      efficient targeting and recycling of Mfd and expedient conflict resolution.

PMID- 29224784
TI  - Ethics-based global health research for all, including women, children,
      indigenous people, LGBTQI, people with disabilities, refugees and other relevant
      stakeholders, especially in least developing countries and small island
      developing states in the Global South.

PMID- 29224783
TI  - In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic
      Modulation.
AB  - Current genome-editing systems generally rely on inducing DNA double-strand
      breaks (DSBs). This may limit their utility in clinical therapies, as unwanted
      mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has
      recently been repurposed to enable target gene activation, allowing regulation of
      endogenous gene expression without creating DSBs. However, in vivo implementation
      of this gain-of-function system has proven difficult. Here, we report a robust
      system for in vivo activation of endogenous target genes through trans-epigenetic
      remodeling. The system relies on recruitment of Cas9 and transcriptional
      activation complexes to target loci by modified single guide RNAs. As proof-of
      concept, we used this technology to treat mouse models of diabetes, muscular
      dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9
      mediated target gene activation can be achieved in vivo, leading to measurable
      phenotypes and amelioration of disease symptoms. This establishes new avenues for
      developing targeted epigenetic therapies against human diseases. VIDEO ABSTRACT.

PMID- 29224785
TI  - Incongruence between molecules and morphology: A seven-gene phylogeny of Dacini
      fruit flies paves the way for reclassification (Diptera: Tephritidae).
AB  - Molecular and morphological research often suggest conflicting results. Selective
      pressure on certain morphologies can confound understanding of evolutionary
      relationships. Dacini is one of the most diverse tribes of tephritid flies and
      contains many economically important pest species. Their black and yellow
      patterned body markings are presumed to act as wasp mimicry, and the characters
      separating species and groups are limited and in some cases phenotypically
      plastic. The traditional taxonomy of the tribe is controversial because groupings
      are based on unique combinations of morphological characters without the use of
      cladistic methods, though recent phylogenetic and taxonomic analyses have
      resulted in significant changes to their taxonomy. The monophyly of the three
      largest genera in the tribe has been tested with only small numbers of
      representatives per genus and a limited number of genes. To further understand
      the taxonomy and evolution of Dacini we sequenced seven genes from 167 Dacini
      species and five dipteran outgroups to construct a robust phylogeny and test
      phylogenetic relationships between genera, subgenera, and species complexes. Our
      phylogeny confirms the monophyly of Dacus, Bactrocera, and Zeugodacus. However,
      most groups below the genus level are not monophyletic, and only through further
      revision will we be able to understand their evolution and clarify the taxonomy
      within this tribe.

PMID- 29224786
TI  - Multi-locus reassessment of a striking discord between mtDNA gene trees and
      taxonomy across two congeneric species complexes.
AB  - Resolving relationships among members of the yellow and citrine wagtail species
      complexes is among the greatest challenges in avian systematics due to arguably
      the most dramatic disagreements between traditional taxonomy and mtDNA phylogeny.
      Each species complex is divided into three geographically cohesive mtDNA clades.
      Each clade from one species complex has a sister from the other complex.
      Furthermore, one cross-complex pair is more distantly related to the remaining
      two pairs than are several other wagtail species. To test mtDNA gene tree
      topology, we sequenced the mtDNA ND2 gene and 11 nuclear introns for seven
      wagtail species. Our mtDNA gene tree reconstruction supported the results of
      previous studies, thereby confirming the disagreement between mtDNA phylogeny and
      taxonomy. However, our multi-locus species tree which used mtDNA clades as "taxa"
      was consistent with traditional taxonomy regardless of whether mtDNA was included
      in the analysis or not. Our multi-locus data suggest that despite the presence of
      strongly supported, geographically structured mtDNA variation, the mtDNA gene
      tree misrepresents the evolutionary history of the yellow and citrine wagtail
      complexes. This mito-nuclear discord results from mtDNA representing the
      biogeographic, but not evolutionary history of these recently radiated Palearctic
      wagtails.

PMID- 29224787
TI  - Global research output in antimicrobial resistance among uropathogens: A
      bibliometric analysis (2002-2016).
AB  - OBJECTIVES: Antimicrobial resistance (AMR) among uropathogens contributes to
      treatment failure. Research in AMR among uropathogens is important to establish
      treatment options. This study assessed global research trends in AMR among
      uropathogens. METHODS: SciVerse Scopus was used to retrieve relevant documents
      for the period 2002-2016. Only journal articles were included in the analysis.
      Analysis of author keywords was carried out using VOSviewer. RESULTS: A total of
      1087 journal articles were retrieved with an h-index of 50. The number of
      publications increased noticeably in the past decade. Analysis of subject areas
      of retrieved documents showed that 275 (25.3%) articles were in molecular
      biology/genetics/microbiology/immunology, 197 (18.1%) were in
      pharmacological/therapeutic approaches for treatment of urinary tract infections
      and 615 (56.6%) were in epidemiology/public health. Terms such as multidrug
      resistant and extended-spectrum beta-lactamases (ESBLs) appeared more frequently
      in documents published in the period 2012-2016. The mean number of authors per
      article was 5.3. Most active authors in this field were from Japan. The USA
      ranked first with 148 documents (13.6%), followed by India (97; 8.9%) and Iran
      (84; 7.7%). The top productive institution was Tehran University of Medical
      Sciences (21 publications), followed by Kobe University in Japan (20
      publications). The Journal of Antimicrobial Chemotherapy ranked first with 33
      publications. CONCLUSION: Research in AMR among uropathogens showed a noticeable
      increase in the past decade. Reports of increasing incidence of resistance among
      uropathogens were published from different parts of the world. Empirical therapy
      should be based on updated research in AMR.

PMID- 29224788
TI  - Long-term intestinal obstruction sequelae and growth in children with cystic
      fibrosis operated for meconium ileus: expectancies and surprises.
AB  - BACKGROUND/PURPOSE: In the few studies on intestinal complications and growth of
      cystic fibrosis (CF) patients with a history of meconium ileus (MI), operated MI
      has not been investigated separately. We aimed to investigate the incidence of
      long-term intestinal obstruction sequelae [constipation, distal intestinal
      obstruction syndrome (DIOS)] and growth in CF patients operated for MI. METHODS:
      Retrospective study (1989-2016) including operative diagnoses and procedures,
      constipation and DIOS events, yearly Body Mass Index (BMI) measurements. Outcomes
      were examined in subgroups operated for MI only and for MI with atresia and/or
      volvulus. RESULTS: Of 49 patients followed-up for 15 (mean) years, 5 (10.2%)
      developed constipation and 14 (28.6%) DIOS. BMI was within normal percentiles in
      53 patients over a 10-year follow-up. MI only and MI with atresia and/or volvulus
      did not differ in constipation and/or DIOS incidence (11/34 vs. 7/15, p=0.39) or
      in BMI (p=0.47). Cases with ileocecal valve resection (ICV-R) showed lower
      constipation and/or DIOS incidence than those without ICV-R (0/6 vs. 11/28,
      p=0.02) and no different BMI (p>0.05). CONCLUSIONS: CF patients operated for MI
      were in long-term risk for constipation/DIOS; their growth was normal.
      Interestingly, underlying atresia/volvulus neither increased constipation/DIOS
      risk nor affected growth. Strikingly, ICV-R showed no constipation/DIOS risk and
      no impact on growth. TYPE OF STUDY: Retrospective comparative study. LEVEL OF
      EVIDENCE: III.

PMID- 29224789
TI  - Pediatric surgical capacity building - a pathway to improving access to pediatric
      surgical care in Haiti.
AB  - PURPOSE: Lack of human resources is a major barrier to accessing pediatric
      surgical care globally. Our aim was to establish a model for pediatric surgical
      training of general surgery residents in a resource constrained region.
      MATERIALS/METHODS: A pediatric surgical program with a pediatric surgical
      rotation for general surgery residents in a tertiary hospital in Haiti in 2015
      was established. We conducted twice daily patient rounds, ran an outpatient
      clinic, and provided emergent and elective pediatric surgical care, with tasks
      progressively given to residents until they could run clinic and perform the most
      common elective and emergent procedures. We conducted baseline and post
      intervention knowledge exams and dedicated 1 day a week to teaching and research
      activities. We measured the following outcomes: number of residents that
      completed the rotation, mean pre and post intervention test scores, patient
      volume in clinic and operating room, postoperative outcomes, resident ability to
      perform most common elective and emergent procedures, and resident participation
      in research. RESULTS: Nine out of 9 residents completed the rotation; 987
      patients were seen in outpatient clinic, and 564 procedures were performed in
      children <15years old. There was a 50% increase in volume of pediatric cases and
      a 100% increase in procedures performed in children <4years old. Postoperative
      outcomes were: 0% mortality for elective cases and 18% mortality for emergent
      cases, 3% complication rate for elective cases and 6% complication rate for
      emergent cases. Outcomes did not change with increased responsibility given to
      residents. All senior residents (n=4) could perform the most common elective and
      emergent procedures without changes in mortality and complication rates.
      Increases in mean pre and post intervention test scores were 12% (PGY1), 24%
      (PGY2), and 10% (PGY3). 75% of senior residents participated in research
      activities as first or second authors. CONCLUSIONS: Establishing a program in
      pediatric surgery with capacity building of general surgery residents for
      pediatric surgical care provision is feasible in a resource constrained setting
      without negative effects on patient outcomes. This model can be applied in other
      resource constrained settings to increase human resources for global pediatric
      surgical care provision. LEVEL OF EVIDENCE: III.

PMID- 29224790
TI  - Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse
      model of Hirschsprung disease.
AB  - PURPOSE: Semaphorins are guidance cues for developing neurons, implicated in the
      determination of the migratory pathway of neural crest-derived neural precursors
      during enteric nervous system development. Recently, it has been reported that
      Semaphorin 3A (SEMA3A) expression is up-regulated in the aganglionic colon in
      Hirschsprung disease (HD) patients, suggesting that increased SEMA3A expression
      may be a risk factor for HD. Thus, the aim of our study was to determine the
      expression of SEMA3A using Sox10-Venus mice gut. METHODS: We harvested the gut on
      postnatal day 2 (P2). SOX10-Venus+/EDNRB-/- mice were compared with SOX10
      Venus+/EDNRB+/+ mice as controls. QRT-PCR was performed to determine gene
      expression of SEMA3A (n=8). Fluorescent immunohistochemistry was performed to
      assess protein distribution. RESULTS: On P2, gene expression levels of SEMA3A
      were significantly increased in the HD group compared to controls in the proximal
      and distal colon (p<0.05). Laser scanning microscopy revealed SEMA3A expression
      was localized within the submucosa and muscle layer of the gut in both HD and
      controls. In HD, SEMA3A was highly expressed in the proximal and distal colon.
      CONCLUSIONS: In the present study, we demonstrated that SEMA3A expression is
      increased in the EDNRB-/- HD model on P2, suggesting that SEMA3A may interfere
      with ENCC migration, resulting in an absence of enteric neurons.

PMID- 29224791
TI  - Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation
      abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug
      methotrexate in rats.
AB  - BACKGROUND: Methotrexate (MTX) is an efficacious anticancer agent constrained in
      clinical use due to its toxicity on non-targeted tissue, a considerable source of
      worry to clinicians. Because the toxicity is associated with oxidative stress and
      inflammation, the study explored antioxidant and anti-inflammatory effect of
      virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in
      rats. METHODS: Rats were randomized into 4 groups (n=6) as follows: Control
      group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO
      (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected
      with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection,
      serum kidney markers, renal activities of antioxidant enzymes and glutathione
      (GSH) content were determined. Lipid peroxidation level and inflammatory markers-
      interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were
      estimated in kidney. Histopathological alterations were examined for kidney
      damage. RESULTS: MTX nephrotoxicity was evidenced by markedly elevated serum
      renal markers along with significant decreases in renal GSH and activities of
      antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6,
      NO and CRP markedly increased compared to control. VCO supplementation prior to
      MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent
      increases in GSH and antioxidant enzyme activities in a dose-dependent manner.
      The renal inflammatory markers and MDA depleted considerably compared to MTX
      control group. Histopathological alterations were mitigated to confirm the
      biochemical indices. CONCLUSION: VCO supplementation demonstrates
      nephroprotective activity by attenuating MTX oxidative nephrotoxicity via
      antioxidant and anti-inflammatory activities in kidney. Our results suggested
      that VCO may benefit cancer patients on MTX chemotherapy against kidney injury.

PMID- 29224792
TI  - White butterfly (Clerodendrum volubile) leaf extract protects against carbon
      tetrachloride-induced hepatotoxicity in rats.
AB  - Currently, there is increasing attention towards flavonoids and phenolic
      compounds of plant origin because of their association with decrease in the
      incidence of cardiovascular diseases and different types of cancer. The present
      study investigates the protective effect of Clerodendrum volubile (C. volubile)
      methanolic extracts against carbon tetrachloride (CCl4)-induced hepatotoxicity in
      rats. Control rats (group I) received olive oil (1 mL/kg, i.p.), group II
      received CCl4 in olive oil (1 ml/kg, i.p.) to induce hepatotoxicity, groups III,
      IV and V were pretreated with leaf extract of C. volubile at 125 mg/kg, 250 mg/kg
      and 500 mg/kg body weight respectively for 14 days prior to CCl4 administration,
      group VI received vitamin E (100 mg/kg, p.o.) as standard antioxidant to compare
      with antioxidant effects of the extract. CCl4 hepatotoxicity, characterized by
      significant (P < 0.05) increase in the levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), and alkaline phosphatase (ALP), hepatic
      degeneration, and inflammation was attenuated by C. volubile methanolic extracts.
      The serum lipid parameters which include high density lipoprotein (HDL) and low
      density lipoprotein (LDL) were significantly (P < 0.05) decreased, and increased
      respectively by CCl4. Methanolic extracts of C. volubile significantly prevented
      the decrease in the level of HDL and the increase in LDL in a dose-dependent
      manner (P < 0.05). Decrease in total protein induced by CCl4 was moderately
      increased following administration of methanolic extracts of C. volubile. Lipid
      peroxidation was significantly (P < 0.05) reduced while the reduced glutathione
      (GSH) level and the activities of hepatic antioxidant enzymes (catalase,
      superoxide dismutase, and glutathione peroxidase) were significantly elevated by
      C. volubile extract in the CCl4-treated rats. Our findings indicate that C.
      volubile extract has a significant protective effect against CCl4-induced
      hepatotoxicity in rats which may be due to its antioxidant properties which is
      comparable to the reference antioxidant, vitamin E, used in this study.

PMID- 29224793
TI  - Validity of the toddler feeding questionnaire for measuring parent authoritative
      and indulgent feeding practices which are associated with stress and health
      literacy among Latino parents of preschool children.
AB  - Understanding the contribution of parental feeding practices to childhood obesity
      among Latino children is a solution-oriented approach that can lead to
      interventions supporting healthy childhood growth and lowering rates of obesity.
      The purpose of this study was to confirm the reliability and validity of the
      Toddler Feeding Questionnaire (TFQ) to measure parental feeding practices among a
      sample of Spanish-speaking parent-preschool child pairs (n = 529), and to test
      the hypothesis that parent characteristics of body mass index (BMI), stress, and
      health literacy are associated with more indulgent and less authoritative feeding
      practices. Standardized parent-report questionnaires were completed during
      baseline interviews in a randomized controlled trial of an obesity prevention
      intervention. The TFQ includes subscales for indulgent practices (11 items),
      authoritative practices (7 items), and environmental influences (6 items) with
      response options scored on a 5-point Likert scale and averaged. Factor analysis
      confirmed a three-factor structure. Internal consistency was good for indulgent
      (alpha = 0.66) and authoritative (alpha = 0.65) practices but lower for
      environmental (alpha = 0.48). Spearman correlation showed indulgent practices and
      environmental influences were associated with unhealthy child diet patterns,
      whereas authoritative practices were associated with a healthier child diet.
      Multivariate linear regression showed higher parent stress was associated with
      higher indulgent and lower authoritative scores; higher parent health literacy
      was positively associated with indulgent scores. These results indicate the TFQ
      is a valid measure of authoritative and indulgent parent feeding practices among
      Spanish-speaking parents of preschool-age children and that stress and health
      literacy, potentially modifiable parent characteristics, could be targeted to
      support healthy feeding practices.

PMID- 29224795
TI  - Best Practices for Surgeons' Social Media Use: Statement of the Resident and
      Associate Society of the American College of Surgeons.

PMID- 29224794
TI  - External Validation of the European Hernia Society Classification for
      Postoperative Complications after Incisional Hernia Repair: A Cohort Study of
      2,191 Patients.
AB  - BACKGROUND: Incisional hernia is a frequent complication after midline
      laparotomy. Surgical hernia repair is associated with complications, but no clear
      predictive risk factors have been identified. The European Hernia Society (EHS)
      classification offers a structured framework to describe hernias and to analyze
      postoperative complications. Because of its structured nature, it might prove to
      be useful for preoperative patient or treatment classification. The objective of
      this study was to investigate the EHS classification as a predictor for
      postoperative complications after incisional hernia surgery. STUDY DESIGN: An
      analysis was performed using a registry-based, large-scale, prospective cohort
      study, including all patients undergoing incisional hernia surgery between
      September 1, 2011 and February 29, 2016. Univariate analyses and multivariable
      logistic regression analysis were performed to identify risk factors for
      postoperative complications. RESULTS: A total of 2,191 patients were included, of
      whom 323 (15%) had 1 or more complications. Factors associated with complications
      in univariate analyses (p < 0.20) and clinically relevant factors were included
      in the multivariable analysis. In the multivariable analysis, EHS width class,
      incarceration, open surgery, duration of surgery, Altemeier wound class, and
      therapeutic antibiotic treatment were independent risk factors for postoperative
      complications. Third recurrence and emergency surgery were associated with fewer
      complications. CONCLUSIONS: Incisional hernia repair is associated with a 15%
      complication rate. The EHS width classification is associated with postoperative
      complications. To identify patients at risk for complications, the EHS
      classification is useful.

PMID- 29224796
TI  - Residents' Impressions of the Impact of Advanced Practice Providers on Surgical
      Training.
AB  - BACKGROUND: To ensure that residents are appropriately trained in the era of the
      80-hour work-week, training programs have restructured resident duties and hired
      advanced practice providers (APPs). However, the effect of APPs on surgical
      training remains unknown. STUDY DESIGN: We created a survey using a modified
      Delphi technique to examine the interaction between residents and APPs across
      practice settings (inpatient, outpatient, and operating room). We identified the
      following domains: administrative tasks, clinical experience, operative
      experience, and overall impressions. We administered the survey to residents
      across 7 surgical training programs at a single institution and assessed internal
      reliability with Cronbach's alpha. RESULTS: Fifty residents responded (77%
      participation rate). The majority reported APPs reduced the time spent on
      administrative tasks, such as completing documentation (96%) and answering pages
      (88%). For clinical experience, 62% of residents thought that APPs had no impact
      on the amount of time spent evaluating consult patients, and 80% reported no
      difference in the number of bedside procedures performed. However, 77% of
      residents reported a reduction in the time spent counseling patients. When APPs
      worked in the inpatient setting, 90% of residents reported leaving the operating
      room less frequently to manage patients. When APPs were present in the operating
      room, 34% of residents thought they were less likely to perform key parts of the
      case. Cronbach's alpha showed excellent to good reliability for the
      administrative tasks (0.96), clinical experience (0.76), operative experience
      (0.69), and overall impressions (0.66) domains. CONCLUSIONS: Most residents
      report that the integration of APPs has decreased the administrative burden. The
      reduction in patient counseling might be an unrecognized and unintended
      consequence of implementing APPs. The perceived effect on operative experience is
      dependent on the role of the APPs.

PMID- 29224797
TI  - Kidney Transplantation With and Without Native Nephrectomy for Polycystic Kidney
      Disease: Results of the National Inpatient Sample and the Rationale for a 2
      Staged Procedure.
AB  - BACKGROUND: Polycystic kidney disease (PKD) is one of the most common causes of
      end-stage renal disease requiring hemodialysis or transplantation. In patients
      requiring transplantation, there are several indications for native nephrectomy,
      including recurrent cyst infection, bleeding, or to provide room for the graft.
      There is disagreement about whether it is advisable to perform kidney
      transplantation alone (KT), or to perform KT with simultaneous native nephrectomy
      (KTN). We compared postoperative outcomes of KTN and KT in a large national
      cohort. STUDY DESIGN: The Nationwide Inpatient Sample (NIS) between 2000 and 2014
      was examined for a diagnosis of PKD with evidence for KT or KTN. Logistic
      regression, adjusting for age, sex, comorbidity, and hospital region, was used to
      compare groups for the need for blood transfusion, need for critical care
      interventions, and development of postoperative complications. RESULTS: A total
      of 4,003 hospitalizations were identified, which was representative of 19,302
      weighted discharges nationally. In adjusted logistic regression models, KTN
      demonstrated significantly higher risk for blood transfusion (odds ratio [OR]
      2.06; 95% CI 1.44 to 2.96; p < 0.0001), postoperative complications (OR 1.44; 95%
      CI 1.05 to 1.96; p = 0.02), and critical care interventions (OR 1.44; 95% CI 1.07
      to 1.95; p = 0.02). Other significant predictors for blood transfusion included
      female sex (OR 1.76; 95% CI 1.45 to 2.13; p < 0.0001), age older than 61 years
      (OR 1.60; 95% CI 1.21 to 2.10; p = 0.001), and Charlson comorbidity score >=2 (OR
      1.52; 95% CI 1.10 to 2.09; p = 0.01). CONCLUSIONS: Among patients with PKD, in
      comparison with KTN, KT alone represents a decreased risk for negative
      postoperative outcomes. A 2-staged procedure should be considered, when feasible,
      to minimize adverse patient outcomes.

PMID- 29224798
TI  - Slide Esophagoplasty vs End-to-End Anastomosis for Recalcitrant Esophageal
      Stricture after Esophageal Atresia Repair.
AB  - BACKGROUND: Anastomotic stricture is a common complication after esophageal
      atresia (EA) repair. Patients with a recalcitrant stricture may require surgical
      intervention. The technique of reanastomosis after stricture resection can affect
      patient outcomes. STUDY DESIGN: Patients with EA who underwent anastomotic
      stricture resection, from July 2010 to February 2017, were reviewed. After
      stricture resection, patients who had slide esophagoplasty performed were
      compared with those having conventional end-to-end anastomosis. RESULTS: Fifty
      patients underwent stricture repair surgery by slide esophagoplasty (n = 12) or
      end-to-end (n = 38) anastomosis technique at a median age of 14 months
      (interquartile range [IQR] 6 to 23 months). Significantly fewer patients required
      dilation therapy after slide esophagoplasty: 6 of 12 (50%) compared with 32 of 38
      (84%) in the end-to-end group (p = 0.02). The number of dilation sessions was
      significantly lower in the slide group vs the end-to-end (p = 0.004) group, with
      a risk ratio confirming the approximately half the number of dilations for the
      slide approach (risk ratio 0.57, 95% CI 0.38 to 0.86). Steroid injection was
      combined with dilation in 3 of 12 (25%) vs 22 of 38 (58%) in the slide and end-to
      end groups, respectively (p = 0.10). Stent placement was used in none of slide
      cases vs 8 of 38 (21%) in the end-to-end group (p = 0.17). Stricture incision was
      performed in 1 of 12 (8%) in the slide group and 11 of 38 (29%) in the end-to-end
      group (p = 0.25). There were leak complications in fewer patients after slide
      esophagoplasty compared with end-to-end anastomosis: 1 of 12 (8%) vs 8 of 38
      (21%) (p = 0.43). CONCLUSIONS: Slide esophagoplasty may be a useful technique of
      anastomotic configuration for selected patients with recalcitrant esophageal
      stricture, offering more favorable outcomes compared with end-to-end anastomosis.

PMID- 29224799
TI  - Editorial overview: Gastrointestinal: New frontiers in therapeutics for GI
      diseases and disorders-from microRNAs to novel pharmaceutics, to low FODMAP diets
      and microbiome.

PMID- 29224800
TI  - Editorial overview: Endocrine and metabolic diseases: Busting BMI: new strategies
      for the treatment of obesity and metabolic disease.

PMID- 29224801
TI  - Abraham Lilienfeld Award address: 2017 Annual Meeting of the American College of
      Epidemiology.
AB  - The address was delivered by Roberta B. Ness, MD MPH at the Annual Meeting of the
      American College of Epidemiology in New Orleans, Louisiana on September 26, 2017.
      Dr. Ness is James W. Rockwell Professor of Public Health and Vice-President for
      Innovation at the University of Texas School of Public Health. Recognized
      nationally and internationally for her expertise in women's health research, Dr.
      Ness pioneered the area of "gender-based biology". In more recent years, she
      developed an innovative program at the UT School of Public Health aimed at
      cultivating "outside the box" thinking among training scientists. Dr. Ness has
      authored a range of books on her work, including Health and Disease among Women
      (1999), Innovation Generation (2012), Genius Unmasked (2013) and The Creativity
      Crisis: Reinventing Science to Unleash Possibility (2014). Dr. Ness is Past
      President of both the American College of Epidemiology and American
      Epidemiological Society, an honorary society of epidemiologists. She is also
      former Dean of UTHealth School of Public Health and former Interim Dean at the
      University of Pittsburgh Graduate School of Public Health. Dr. Ness is a frequent
      advisor to the National Institutes of Health (NIH), Centers for Disease Control
      and Prevention (CDC), Agency for Healthcare Research and Quality (AHRQ), and US
      Department of Defense (DOD). She has an MD from Cornell University and MPH from
      Columbia University. Dr. Ness is an elected member of the National Academy of
      Medicine, American Society of Clinical Investigation (ASCI), and Delta Omega
      honorary society.

PMID- 29224802
TI  - Digestive Disorders of the Abomasum and Intestines.

PMID- 29224803
TI  - Salmonella in Dairy Cattle.
AB  - As an infectious, contagious pathogen, Salmonella is probably rivaled by only
      bovine viral diarrhea virus in its ability to cause clinical disease, such as
      enteritis, septicemia, pneumonia, and reproductive losses. The increasing
      prevalence of Salmonella, particularly Salmonella Dublin, on dairies presents new
      challenges to producers and veterinarians. No current discussion of bovine
      salmonellosis is complete without acknowledging the increasing public health
      concern. Increasing antimicrobial resistance among enteric pathogens brings the
      use of antimicrobials by veterinarians and producers under ever stricter
      scrutiny. This article provides a comprehensive review of Salmonella etiology,
      prevalence, pathogenesis, diagnostics, treatment, and control.

PMID- 29224804
TI  - Clinical implications of pathologic factors after thyroid lobectomy in patients
      with papillary thyroid carcinoma.
AB  - OBJECTIVE: We evaluated the clinical and prognostic significance of pathologic
      factors by analyzing the treatment results of patients who underwent thyroid
      lobectomy. MATERIALS AND METHODS: We retrospectively analyzed data from 734
      patients diagnosed with papillary thyroid cancer who underwent thyroid lobectomy
      at Korea University Hospital from January 2004 to December 2016. RESULTS: A total
      of 734 patients were included in the study and their mean age was 44.5 years
      (range, 15-83). On univariate analysis, tumor size and recurrence-free survival
      were significantly related. The 10-year recurrence-free survival was 98.3% for
      tumors <=1cm, 77.8% for >1cm and <=2cm, and 66.7% for >2cm (p = 0.014).
      Recurrence-free survival was significantly different between patients with and
      without microscopic extrathyroidal extension (p=0.002). The 10-year recurrence
      free survival rate was 99.2% for patients without extrathyroidal extension and
      92.2% for patients with microscopic extrathyroidal extension. Multivariate
      analysis showed only microscopic extrathyroidal extension was significantly
      correlated with recurrence-free survival (p=0.029). CONCLUSION: In patients
      undergoing thyroid lobectomy for low-risk papillary thyroid cancer, microscopic
      extrathyroidal extension was an important prognostic factor associated with
      recurrence-free survival. However, in cases with microscopic extrathyroidal
      extension findings on postoperative pathologic examination, appropriate
      ultrasonographic follow-up of the contralateral thyroid lobe and cervical lymph
      node to facilitate early detection and prompt treatment of recurrence can control
      the disease without a deterioration of survival rate.

PMID- 29224805
TI  - Prognostic value of masticatory muscle involvement in nasopharyngeal carcinoma
      patients treated with intensity-modulated radiation therapy.
AB  - BACKGROUND AND PURPOSE: In 2017, the 8th edition of the nasopharyngeal carcinoma
      (NPC) staging manual published by the Union for International Cancer
      Control/American Joint Committee on Cancer (UICC/AJCC) defined new rules
      regarding the involvement of anatomical masticatory muscles (MM). The purpose of
      this study is to evaluate the validity of the current T-staging system after the
      addition of revisions regarding MM involvement. METHODS: We performed a
      retrospective review of 608 patients, who were newly diagnosed with NPC and
      treated with intensity-modulated radiotherapy (IMRT) between January 2008 and
      March 2010. RESULTS: We found MM involvement in 398 NPC cases (65.4%). We
      observed a significant difference in overall survival (OS; 75.6% vs. 86.7%, P =
      .043) and in local relapse-free survival (LRFS; 81.5% vs. 88.6%, P = .048)
      between patients with and without MM involvement, but no difference in distant
      metastasis-free survival (DMFS; 80.3% vs. 85.0%, P = .147) or disease-free
      survival (DFS; 77.9% vs. 81.6%, P = .081). Significant differences in OS and LRFS
      were also found among different types of MM involvement. Compared with patients
      who had concurrent involvement of the lateral pterygoid muscle (LP), patients
      with tumors invading only the medial pterygoid muscle (MP) had a higher OS and
      LRFS rates, according to univariate and multivariate analysis (P < .05).
      CONCLUSIONS: MM involvement is an independent prognostic factor for OS and LRFS.
      We conclude that the decision to down-stage MP as T2 in the 8th edition staging
      system is valid. However, tumors with LP involvement were more rational
      classified into a higher T-staging category than tumors with only-MP involvement.

PMID- 29224806
TI  - Oncogenic DNA viruses found in salivary gland tumors.
AB  - BACKGROUND: Previous investigations studying the association of DNA viruses with
      salivary gland tumors (SGTs) have led to conflicting results. The aim of this
      study was to determine the prevalence of different DNA viruses by using a highly
      sensitive assay in a multi-center series of over 100 fresh frozen salivary gland
      samples. METHODS: DNA was isolated from 84 SGTs (80 parotid tumors and 4
      submandibular gland tumors) and 28 normal salivary tissue samples from 85
      patients in Northeast Italy. Using a highly sensitive type-specific multiplex
      genotyping assay, we analyzed the samples for the presence of DNA from 62
      different viruses including 47 papillomaviruses, 10 polyomaviruses, and 5
      herpesviruses. RESULTS: We observed a high prevalence of beta human
      papillomavirus DNA in malignant tumors. In contrast, polyomavirus DNA was present
      in benign, malignant, and non-tumor control samples. Most striking was the
      significant distribution of herpesvirus DNA in the SGT samples, in particular the
      high prevalence of Epstein-Barr type 1 and type 2 DNA in Warthin's tumor samples.
      CONCLUSION: Our data provides evidence for the presence of DNA viruses in SGTs.
      Mechanistic studies are needed to further attribute tumor formation to these
      viruses.

PMID- 29224807
TI  - Construction of mass spectra database and diagnosis algorithm for head and neck
      squamous cell carcinoma.
AB  - OBJECTIVES: Intraoperative identification of tumor margins is essential to
      achieving complete tumor resection. However, the process of intraoperative
      pathological diagnosis involves cumbersome procedures, such as preparation of
      cryosections and microscopic examination, thus requiring more than 30 min.
      Moreover, intraoperative diagnoses made by examining cryosections are
      occasionally inconsistent with postoperative diagnoses made by examining paraffin
      embedded sections because the former are of poorer quality. We sought to
      establish a more rapid accurate method of intraoperative assessment. MATERIALS
      AND METHODS: A diagnostic algorithm of head and neck squamous cell carcinoma
      (HNSCC) using machine learning was constructed by mass spectra obtained from 15
      non-cancerous and 19 HNSCC specimens by probe electrospray ionization mass
      spectrometry (PESI-MS). The clinical validity of this system was evaluated using
      intraoperative specimens of HNSCC and normal mucosa. RESULTS: A total of 114 and
      141 mass spectra were acquired from non-cancerous and cancerous specimens,
      respectively, using both positive- and negative-ion modes of PESI-MS. These data
      were fed into partial least squares-logistic regression (PLS-LR) to discriminate
      tumor-specific spectral patterns. Leave-one-patient-out cross validation of this
      algorithm in positive- and negative-ion modes showed accuracies in HNSCC
      diagnosis of 90.48% and 95.35%, respectively. In intraoperative specimens of
      HNSCC, this algorithm precisely defined the borders of the cancerous regions;
      these corresponded with those determined by examining histologic sections. The
      procedure took approximately 5 min. CONCLUSION: This diagnostic system, based on
      machine learning, enables accurate discrimination of cancerous regions and has
      the potential to provide rapid intraoperative assessment of HNSCC margins.

PMID- 29224808
TI  - Delayed clinical complete response to intensity-modulated radiotherapy in
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: Twelve weeks after radiotherapy is the recommended time-point for
      assessing tumor response in nasopharyngeal carcinoma (NPC); however, regression
      after 12 weeks remains unclear. We explored NPC regression and the prognosis of
      patients with delayed clinical complete response (cCR). MATERIALS AND METHODS:
      MRI images of 556 NPC patients treated with intensity-modulated radiotherapy
      (IMRT) between 2009 and 2012 were retrospectively reviewed. Clinical tumor
      response was assessed at 3-4 (assessment 1) and 6-9 months (assessment 2) after
      IMRT, and survival rates were compared. RESULTS: Of the 556 patients, 463 (83.3%)
      had cCR at assessment 1 (early cCR). Of the 93 patients with partial response at
      assessment 1, 45 (48.4%) achieved cCR at assessment 2 (delayed cCR), and 48 did
      not have cCR at assessment 2 (non-cCR). Locoregional failure rate was lower in
      patients with a cCR than those without a cCR at assessment 1 (7.1% vs. 26.9%, P <
      .001) and assessment 2 (7.1% vs. 45.8%, P < .001). Multivariate analysis showed
      cCR was a favorable prognostic factor for locoregional failure-free survival
      (LRFFS), failure-free survival (FFS), and overall survival (OS). Early and
      delayed cCR groups had better 5-year LRFFS (92.6% vs. 93.3% vs. 54.2%), FFS
      (83.8% vs. 84.4% vs. 48.5%) and OS (92.1% vs. 90.6% vs. 65.4%) than the non-cCR
      group (all P < .001). CONCLUSIONS: Nearly half of the patients with partial
      response at 3-4 months achieve cCR by 6-9 months; delayed cCR is not a poor
      prognosticator. We suggest later assessment of cCR at 6-9 months after IMRT is
      acceptable in responding NPC.

PMID- 29224809
TI  - Unplanned readmission following transoral robotic surgery.
AB  - OBJECTIVES: To determine the rate of unplanned readmission after transoral
      robotic surgery (TORS), and to determine which patient or surgical factors
      increase the likelihood of readmission. MATERIALS AND METHODS: Retrospective
      chart review of all patients who underwent TORS for squamous cell carcinoma at
      our institution from March 2010 through July 2016. Primary outcome was unplanned
      readmission to the hospital within 30 days of discharge. Univariable and
      multivariable logistic regression were performed to identify risk factors for
      unplanned readmission. RESULTS: 297 patients met eligibility criteria. 23
      patients (7.7%) had unplanned readmissions within 30 days. Most common reasons
      for readmission were oropharyngeal bleed (n = 13) and pain/dehydration (n = 10).
      Average time to unplanned readmission was 6.52 days (range 0-25 days). Discharge
      on clopidogrel was the only variable independently associated with an increased
      risk of 30-day unplanned readmission on multivariable analysis with an OR = 6.85
      (95% CI 1.59-26.36). Unplanned return to the operating room during initial
      hospitalization (OR = 7.55, 95% CI 1.26-38.50) and discharge on clopidogrel (OR =
      10.45, 95% CI 1.06-82.69) were associated with increased risk of postoperative
      bleeding. Bilateral neck dissection (OR = 5.17, 95% CI 1.15-23.08) was associated
      with significantly increased odds of unplanned readmission secondary to pain and
      dehydration. CONCLUSION: Unplanned readmission following TORS occurs in a small
      but significant number of patients. Oropharyngeal bleeding and dehydration were
      the most common reasons for unplanned readmission following TORS.

PMID- 29224810
TI  - Utilization of a pre-bent plate-positioning surgical guide system in precise
      mandibular reconstruction with a free fibula flap.
AB  - OBJECTIVES: We evaluated the effects of three-dimensional virtual planning and
      the use of a plate-embedded surgical guide in mandibular reconstruction with
      microvascular fibula flaps. MATERIALS AND METHODS: We retrospectively reviewed 35
      patients who underwent primary mandibular reconstruction with a free fibula flap.
      They were divided into three groups according to the therapy they received. In
      group A, 12 patients underwent reconstruction using the modified surgical guide
      system, including virtual surgeries, pre-bent titanium plates, screw
      predesignated cutting guides for mandibular and fibular osteotomies, and plate
      embedded shaping guides. In group B, 14 patients underwent reconstruction using
      the common surgical guide system, including virtual surgeries, cutting guides and
      pre-bent plates. In group C, 9 patients underwent reconstruction based on the
      surgeon's experience. All cases were reviewed for the total operative time,
      ischemia time of the fibula flaps, accuracy of surgery, and postoperative
      complications. RESULTS: All of the fibula flaps survived. In group A, the
      ischemia time was shorter than that of groups B and C (P < .05). The average
      gonion and condyle shift was lower in group A than in groups B and C (P < .01).
      CONCLUSIONS: Application of the screw-predesignated and plate-embedded surgical
      guide system can reduce the ischemia time and operation time in mandibular
      reconstruction with a fibula flap, and can increase reconstruction accuracy. This
      method is a precise and highly reliable technique for improving the clinical
      outcome of mandibular reconstruction.

PMID- 29224811
TI  - Cancer stem cell and its niche in malignant progression of oral potentially
      malignant disorders.
AB  - OBJECTIVE: The purpose of this study was to determine association between cancer
      stem cells (CSCs) and their niche with progression of oral potentially malignant
      disorders. MATERIALS AND METHODS: Patients with histologically confirmed oral
      potentially malignant disorders, stratified into high/low risk lesions based on
      the degree of dysplasia and oral cancer were included in this study.
      Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31)
      and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical
      analysis was performed to correlate the relationship of markers with
      histopathology grade (ANOVA, and chi2 test, unpaired t test) using GraphPad
      InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis
      showed progressive increase in expression levels of CSC and its niche markers
      with increase in grade of dysplasia as compared to the normal cohort (p < 0.05).
      Co-expression analysis revealed that, in comparison to the normal cohort, a
      larger percentage of patients showed increased expression of CD31 and CD44
      (CD31high/CD44high; p < 0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; p =
      0.04), suggesting an association of the CSCs and the vascular niche. Further,
      distribution of patients with CD44high/CXCR4high (p < 0.05) and CD31high/SDF1high
      (p = 0.01) was significantly increased in the high-risk group (18%), suggesting a
      correlation between CD44+/CXCR4+ cells, the vascular niche and progression of
      oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the
      vascular niche and their cross talk markers are associated with increase in
      severity of dysplasia suggesting their role in the progression of oral
      potentially malignant disorders and may hence be used in identifying high-risk
      OPMD.

PMID- 29224813
TI  - Psychometric validation of the Center for Epidemiological Studies Depression
      Scale in Head and Neck Cancer patients.
AB  - OBJECTIVE: The Center for Epidemiological Studies Depression Scale (CES-D) is a
      20-item tool developed to screen for depression in the general population. To
      psychometrically evaluate and validate the CES-D scale for use in head and neck
      cancer (HNC) patients. METHODS: The CES-D was applied to 130 subjects at onset of
      radiation treatment and 3-months following treatment. Analysis was conducted via
      face and content validity using two expert raters, internal consistency was
      applied using Cronbach's alpha, test retest reliability comparing baseline to 3
      month application, concurrent validity was performed against the FACT-H&N and
      Pain Disability Index, construct validity was conducted via exploratory factor
      analysis. RESULTS: The sample was predominantly male receiving chemo radiation.
      Face validity was strong (alpha = 0.85). Significant difference was found in the
      mean score between depressed (CES-D cut point >= 16) vs. non-depressed (t = 
      15.84, p = .00) (95% CI = -17.18, -13.33). Internal consistency of the scale was
      high (alpha = 0.84). Test retest reliability (p < .001) showed moderate-strong
      correlations (0.51), however was not sensitive to change in this sample across
      the study time period. Concurrent validity was strong (r = -0.77, 0.51). Factor
      analysis at baseline explained 54.92% of variance, with 3 distinct factors;
      depressed affect, somatic/retarded activity, and positive affect. In contrast to
      general populations, the factor 'disturbed interpersonal skill' was not retained.
      CONCLUSION: Results confirm the reliability and validity of the CES-D as a
      measure of depression in HNC populations. Proposed cut off scores remain stable
      but scale responsiveness suggests caution when evaluating change over time in
      this population.

PMID- 29224812
TI  - Differential roles of kallikrein-related peptidase 6 in malignant transformation
      and DeltaNp63beta-mediated epithelial-mesenchymal transition of oral squamous
      cell carcinoma.
AB  - We previously reported that epithelial-to-mesenchymal transition (EMT) was
      mediated by DeltaNp63beta in oral squamous cell carcinoma (OSCC). In this study,
      DNA microarray analyses were performed using DeltaNp63beta-overexpressing OSCC
      cells to identify genes associated with DeltaNp63beta-mediated EMT. Thereby, we
      focused on kallikrein-related peptidase (KLK) 6, most up-regulated following
      DeltaNp63beta-overexpression, that activates protease-activated receptors (PARs).
      In RT-PCR analyses, DeltaNp63 was positively associated with KLK6 and PAR2 and
      negatively with PAR1 in OSCC cells. By DeltaNp63 knockdown, KLK6 and PAR2
      expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led
      to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT
      phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK
      was reduced, it was restored in the KLK6 knockdown OSCC cells treated with
      recombinant KLK6 proteins. Immunohistochemistry showed DeltaNp63, KLK6, and PAR2
      were more strongly expressed in the epithelial dysplasia and central region of
      OSCC than normal oral epithelium, whereas PAR1 expression was undetectable.
      Interestingly, at the invasive front of OSCC, DeltaNp63, KLK6, and PAR2 were
      reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing
      KLK6 expression at the invasive front had more unfavourable prognosis. These
      results suggested differential roles of KLK6 in malignant transformation and EMT;
      high DeltaNp63beta expression up-regulates KLK6-PAR2 and down-regulates PAR1,
      inducing malignant transformation in oral epithelium with stimulating
      proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is
      down-regulated and PAR1 is up-regulated when DeltaNp63beta expression is
      decreased, leading to EMT with enhancing migration and invasion through ERK
      signal reduction at the invasive front.

PMID- 29224814
TI  - Transoral robotic surgery-based therapy in patients with stage III-IV
      oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVE: TORS-based therapy including chemotherapy or RTx was administered to
      patients with stage III-IV OPSCC. We analyzed the oncological and functional
      outcomes of stage III-IV OPSCC patients who underwent TORS-based therapy.
      MATERIALS AND METHODS: Between May 2008 and May 2016, 80 patients participated in
      this clinical trial. RESULTS: A negative margin was identified in 66 patients
      (82.5%) and a positive margin in 14 (17.5%). TNM stages were III in 13 patients
      (16.3%) and IV in 67 patients (83.8%). Of the patients, 13 received surgery
      alone, 28 had adjuvant RTx and 39 had adjuvant CCRTx. At last follow-up, 67
      patients had no evidence of disease, seven were alive with disease, and six had
      died. Local recurrence developed in 2 patients and regional recurrence in 10.
      Five-year overall survival was 88.8%, disease-specific survival was 89.9%, and
      recurrence-free survival was 78.3%. The 5-year disease-specific survival of OPSCC
      patients with p16+ disease was 93.2%, which was higher than 89.0% of patients
      with p16- disease, but the difference was not statically significant. On
      multivariate analysis, only extranodal extension showed a significant
      relationship with recurrence-free survival on Cox regression analysis.
      CONCLUSION: TORS-based therapy showed excellent oncological and functional
      outcomes for treatment of stage III-IV OPSCC. For advanced T stage OPSCC, clear
      margins were obtained using TORS-based therapy and patients with clear margins
      showed good local control. Risk stratification of patients based on pathological
      information obtained after surgery and decision about additional treatment based
      on the information helped improve OS and DSS of OPSCC patients.

PMID- 29224815
TI  - Definitive (chemo)radiotherapy is a curative alternative for standard of care in
      advanced stage squamous cell carcinoma of the oral cavity.
AB  - OBJECTIVE: To compare outcome after definitive (chemo)radiotherapy (CRT group)
      with standard of care (surgery group) for advanced stage oral cavity carcinoma
      (OCC). Although definitive (chemo)radiotherapy is assumed to be inferior to
      surgery with regard to disease control, data on outcome of this approach are
      scarce. METHODS: Retrospective analysis by chart review (2000-2013). Endpoints
      were locoregional control (LRC), disease-free survival (DFS), disease specific
      survival (DSS) and overall survival (OS). RESULTS: Between the CRT-group (n =
      100) and Surgery-group (n = 109), baseline characteristics were equally
      distributed except stage and local tumor diameter (all p <= .001). In the CRT
      group, at 5 years the LRC rate was 49%, DFS 22%, DSS 39% and OS 22%. In the
      surgery group, at 5 years the LRC rate was 77%, DFS 45%, DSS 64% and OS 45%. The
      survival curves of the two groups significantly differed for LRC (p < .001), DFS
      and DSS (p = .001) and OS (p = .002). After adjusting for confounders and
      prognostic factors, we found a significant difference between the treatment
      groups in LRC (adjusted HR = 2.88, 95%CI 1.35-6.16, p = .006). Within 100 days, 5
      patients (5%) died from treatment-related toxicity in CRT group and 1 patient
      after surgery (p = .21). CONCLUSIONS: Although surgery with adjuvant radiotherapy
      for advanced stage OCC results in favorable locoregional control, definitive
      (chemo)radiotherapy is a curative alternative in patients often considered beyond
      cure and should be considered when surgery is not feasible.

PMID- 29224817
TI  - Reconstruction Special Edition, Issue 2.

PMID- 29224816
TI  - Hypermethylated ZNF582 and PAX1 genes in oral scrapings collected from cancer
      adjacent normal oral mucosal sites are associated with aggressive progression and
      poor prognosis of oral cancer.
AB  - OBJECTIVE: This study assessed whether hypermethylated ZNF582 and PAX1 genes in
      oral scrapings are correlated with the progression and prognosis of oral squamous
      cell carcinoma (OSCC). MATERIALS AND METHODS: Methylation levels of ZNF582 and
      PAX1 genes in oral scrapings, collected from the cancer and adjacent normal oral
      mucosal sites of 80 OSCC patients before surgical cancer excision, were
      quantified using real-time methylation-specific PCR after bisulfite conversion.
      RESULTS: Both the mean methylation (M)-indices of ZNF582 and PAX1 genes in oral
      scrapings were significantly higher at the cancer sites than at the adjacent
      normal oral mucosal sites (both P < .001). In the oral scrapings collected from
      the adjacent normal oral mucosal sites, the higher M-index of methylated ZNF582
      (ZNF582m) was significantly correlated with a more advanced clinical stage (P =
      .04). Moreover, the higher M-index of methylated PAX1 (PAX1m) was significantly
      related to larger tumor size (P = .046). When the 80 OSCC patients were
      classified based on gene methylation tests, using the oral scrapings collected
      from the adjacent normal oral mucosal sites, we found a significantly shorter 3
      year overall survival in ZNF582m-positive, PAX1m-positive, and ZNF582m/PAX1m
      positive OSCC patients than in ZNF582m-negative (P = .02), PAX1m-negative (P =
      .04), and ZNF582m/PAX1m-negative OSCC patients (P = .02), respectively.
      Multivariate Cox regression analyses identified ZNF582m and ZNF582m/PAX1m as
      independent unfavorable prognostic factors. CONCLUSION: Hypermethylated ZNF582
      and PAX1 genes in the oral scrapings collected from adjacent normal oral mucosal
      sites rather than cancer sites are associated with aggressive progression and
      poor prognosis of OSCC.

PMID- 29224818
TI  - Reconstruction after salvage laryngectomy.
AB  - Both early and advanced stage laryngeal cancers are treated with organ-preserving
      strategies including radiation alone or concurrent chemoradiotherapy. While organ
      preserving modalities have proven effective in eradicating cancer while also
      preserving laryngeal function, there remains a proportion of cases where residual
      or recurrent cancer prevails, or conversely, where radiotherapy renders a larynx
      dysfunctional. In these circumstances, salvage total laryngectomy is often the
      surgical treatment. The effects of radiotherapy to the neck, amplified by
      chemotherapy, can create an inhospitable surgical environment, making the salvage
      laryngectomy an operation fraught with the potential for major complications such
      as the dreaded pharyngocutaneous fistula. The introduction of vascularized tissue
      from outside the irradiated field decreases the risk of major wound
      complications. Free tissue transfer, with a variety of donor sites available, is
      commonly employed to reconstruct either a patch or a circumferential segment of
      the pharynx. When there is enough pharyngeal mucosa for primary closure, a
      vascularized onlay graft or a pharyngeal interposition graft can be used to
      reinforce the closure. This has been demonstrated to both reduce the severity of
      pharyngocutaneous fistula and decrease the risk of developing a pharyngocutaneous
      fistula compared to primary closure alone. Beyond mitigating the risk for
      perioperative complications, flap selection may have implications on the long
      term outcomes after salvage total laryngectomy and these must be considered
      preoperatively. The purpose of this review is to examine the various options for
      reconstruction after salvage total laryngectomy and to examine some of their
      advantages and disadvantages in the short and long-term.

PMID- 29224819
TI  - Outcome by treatment modality in sinonasal undifferentiated carcinoma (SNUC): A
      case-series, systematic review and meta-analysis.
AB  - OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is an aggressive
      malignancy first described by Frierson et al. in 1986. As the tumor is very rare,
      current treatment recommendations are based on institutional case reports. We
      thus felt the need to perform a comprehensive systematic review and meta-analysis
      to investigate how treatment modalities are associated with survival. DESIGN:
      Case-series, systematic review and meta-analysis METHODS: We searched the
      OvidMedline, OvidEmbase, Web of Science, Biosis, Scopus and the Cochrane Library
      database libraries. We extracted aggregate and individual patient data for
      statistical analysis. To study the association between treatment modalities and
      survival, we used random-effects meta-regression for the aggregate- and cox mixed
      effects models. RESULTS: 379 citations were found; 29 case series could be
      included in the final analysis, including a total number of 390 single patients
      (34.6% female). Median age at diagnosis was 52 years. 80.9% of patients presented
      with a T4 tumor and 16.0% with nodal metastasis at diagnosis. In individual
      patient data (IPD) meta-analysis, single modality (surgery alone or radiation
      alone) treatment was associated with reduced survival compared to double modality
      (surgery & radiation or chemoradiation) treatment (adjusted Hazard Ratio [aHR]
      2.97, 95% ConfidenceInterval [1.41-6.27]) and compared to triple modality
      (surgery & radiation & chemotherapy) treatment (aHR 2.80 95%-CI 1.29-6.05 for
      triple vs. single modality). Triple modality treatment was not superior to double
      modality treatment. (aHR 1.06, 95%-CI 0.59-1.92). CONCLUSION: Double and triple
      modality treatment are associated with improved survival over single modality but
      there is no evidence that triple modality is superior to double modality
      treatment.

PMID- 29224820
TI  - Risk of contralateral nodal failure following ipsilateral IMRT for node-positive
      tonsillar cancer.
AB  - PURPOSE: To determine the risk of contralateral nodal failure following
      ipsilateral radiotherapy in a series of patients with node-positive tonsillar
      squamous cell carcinoma. METHODS: Retrospective review was used to identify 34
      patients with well-lateralized node-positive tonsillar squamous cell carcinoma
      treated with definitive or adjuvant radiation to the primary site and ipsilateral
      neck between 2005 and 2015. Contralateral nodal failure, locoregional recurrence,
      distant metastasis, and overall survival were calculated using actuarial and/or
      cumulative incidence statistics. RESULTS: At last follow-up, contralateral nodal
      failure was only observed in 1 patient (3%) with N1 disease. At median follow-up
      of 34 months for surviving patients, the 3-year overall survival probability was
      87%, and the 3 year cumulative incidences of locoregional failure and distant
      metastasis were 6.5% and 7.2%, respectively. No disease-free patient was
      permanently gastrostomy-dependent. CONCLUSION: Ipsilateral radiation treatment
      with IMRT is effective in node-positive patients with well-lateralized tonsillar
      cancer, resulting in a low risk of contralateral regional recurrence, even in
      patients with N2b disease.

PMID- 29224821
TI  - A multicenter study of malignant oral and maxillofacial lesions in children and
      adolescents.
AB  - OBJECTIVES: To investigate the frequency of malignant oral and maxillofacial
      lesions among children and adolescents from representative geographic regions of
      Brazil. MATERIALS AND METHODS: A retrospective study was conducted on biopsies
      obtained from 1990 to 2016 at six Brazilian oral and maxillofacial pathology
      referral centers. A total of 85,105 biopsy specimens from children and
      adolescents were analyzed. Gender, age, anatomical location, symptomatology and
      histopathological diagnosis were evaluated. Data were analyzed using descriptive
      statistical methods. RESULTS: Fifty-eight (0.06%) malignant oral and
      maxillofacial lesions were diagnosed in children (19%) and adolescents (81%). The
      lesions were more frequent among females (60.3%) and adolescents. The most
      prevalent lesions were mucoepidermoid carcinomas (22.4%), osteosarcomas (13.8%),
      squamous cell carcinomas (12.1%), and Burkitt's lymphomas (12.1%). The most
      commonly affected sites were the palate (19%), mandible (13.8%), and maxilla
      (13.8%). Almost half the patients were asymptomatic. CONCLUSION: Pediatric oral
      and maxillofacial malignant lesions were infrequent and showed wide diversity,
      with a prevalence of mucoepidermoid carcinomas. Analysis of malignant lesions in
      children and adolescents helps pediatric dentists and oncologists to obtain a
      better understanding of such lesions and to reduce the time for diagnosis, with a
      consequent improvement of prognosis.

PMID- 29224822
TI  - Head and neck reconstruction with free flaps based on the thoracodorsal system.
AB  - The advent or micro-vascular free tissue transfer has facilitated the
      reconstruction of increasingly complex head and neck defects. There are multiple
      donor sites available, each with its' own advantages and disadvantages. However,
      the subscapular system, including the thoracodorsal system, provides the widest
      array of soft tissue and osseous flaps, as well as chimeric options. Its
      advantages include a long pedicle, independently mobile tissue components,
      relative sparing from atherosclerosis, and minimal donor site morbidity. The soft
      tissue flaps available from the thoracodorsal system include the Latissimus
      Dorsi, and Thoracodorsal Artery Perforator flaps, while the Tip of Scapula
      provides the osseous component. This review paper outlines the anatomical basis
      for these flaps, as well as describing their utility in head and neck
      reconstruction.

PMID- 29224823
TI  - Results of a phase II randomized controlled clinical trial comparing efficacy of
      Cabazitaxel versus Docetaxel as second line or above therapy in recurrent head
      and neck cancer.
AB  - BACKGROUND: Cabazitaxel has shown activity in squamous cancer cell lines and in
      taxane resistant cell lines. Hence we planned a phase 2 study to evaluate the
      efficacy of cabazitaxel against Docetaxel in recurrent head and neck cancer, post
      first line treatment. METHODS: This was a phase 2, investigator initiated,
      randomized controlled trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20
      mg/m2), in patients with head and neck cancer with ECOG performance status 0-2
      who have been exposed to at least one line of chemotherapy, involving a sample
      size of 92 (46 per group)(CTRI/2015/06/005848). Disease control rate at 6 weeks
      was assessed and compared using the chi-square test. RESULTS: The disease control
      rate at 6 weeks was better in the Docetaxel arm over the cabazitaxel arm (52.3%
      versus 13.6%, p = 0.017). The median progression free survival was 21 days (95%
      CI 5.28 to 36.72 days) in the cabazitaxel arm versus 61 days (95% CI 21.39 to
      100.60 days) in the Docetaxel arm (HR-1.455, 95% CI 0.919-2.304, p = 0.100). The
      median overall survival was 115 days (95% CI 74.04 to 155.95 days) in the
      cabazitaxel arm versus 155 days (95% CI 148.6 to 161.40 days) in the Docetaxel
      arm (HR-1.464, 95% CI 0.849-2.523, p = 0.170). CONCLUSION: Docetaxel had a
      superior disease control rate at 6 weeks compared to cabazitaxel.

PMID- 29224824
TI  - Circulating tumour cell PD-L1 test for head and neck cancers.
AB  - Immune checkpoint inhibitors have gained traction over the last few years in the
      treatment of metastatic/recurrent head and neck squamous cell carcinoma (HNSCC)
      patients. Monoclonal antibodies that block the programmed death 1 (PD-1) receptor
      and its major ligand, PD-L1, have shown durable responses and low toxicity
      profiles. There are currently no validated predictive biomarkers to select
      patients likely to respond to anti-PD-1/PD-L1 therapy to avoid unwanted side
      effects and to reduce healthcare expenditure. A circulating tumour cell (CTC) PD
      L1 assay could be developed as a companion diagnostic tool to potentially predict
      the efficacy of immune checkpoint blockade treatments.

PMID- 29224825
TI  - Head and neck free flap reconstruction: What is the appropriate post-operative
      level of care?
AB  - Patients undergoing head and neck reconstruction require complex,
      multidisciplinary postoperative care which may include wound care, flap
      monitoring, tracheostomy management, and management of comorbid conditions.
      Historically, patients undergoing major resection of a head and neck or
      aerodigestive tract malignancy with regional or free flap reconstruction were
      routinely admitted to the ICU. Although head and neck cancer patients may have
      multiple medical comorbidities that may require postoperative critical care, the
      current trend in many institutions is to transfer stable and less medically
      complex patients to non-intensive care-level units with specialty trained nursing
      staff. These units have been shown to decrease the total cost of care without
      compromising the quality of care, length of stay, or postoperative complications.

PMID- 29224826
TI  - Evaluation of the diagnostic efficacy and spectrum of autofluorescence of benign,
      dysplastic and malignant lesions of the oral cavity using VELscope.
AB  - OBJECTIVES: Conventional oral examination and biopsy are the only reliable
      methods for the early detection of oral cancer at present. Autofluorescence
      examination of oral tissues using the VELscope has been suggested as an
      adjunctive tool for cancer detection and diagnosis. The aim of our study was to
      evaluate the efficacy of the VELscope in recognizing dysplastic and/or neoplastic
      changes in oral mucosal lesions that were identified on conventional oral
      examination. MATERIALS AND METHODS: Two hundred patients with oral mucosal
      lesions were subjected to conventional oral examination followed by VELscope
      examination and their autofluorescence characteristics were compared with the
      histopathological diagnosis. The sensitivity, specificity, positive and negative
      predictive values of the VELscope examination was calculated. RESULTS: The
      VELscope examination showed sensitivity and specificity values of 76% (95% CI:
      54.87-90.64%) and 66.29% (95% CI: 58.76-73.24%) respectively while the positive
      and negative predictive values were 24.36% (95% CI: 19.22-30.36%) and 95.08% (95%
      CI: 90.52-97.51%) respectively. CONCLUSION: The VELscope examination alone cannot
      provide a definitive diagnosis as to the presence of dysplastic tissue change. In
      spite of having a reasonable sensitivity, the high number of false-positive
      results limits its efficiency as an adjunct. However, a high negative predictive
      value can serve to alleviate patient anxiety regarding suspicious mucosal lesions
      in a general practice setting.

PMID- 29224827
TI  - Humidification mitigates acute mucosal toxicity during radiotherapy when
      factoring volumetric parameters. Trans Tasman Radiation Oncology Group (TROG)
      RadioHUM 07.03 substudy.
AB  - PURPOSE/OBJECTIVE(S): To model in a subset of patients from TROG 07.03 managed at
      a single site the association between domiciliary based humidification use and
      mucositis symptom burden during radiotherapy (RT) for head and neck cancer (HNC)
      when factoring in volumetric radiotherapy parameters derived from tumour and
      normal tissue regions of interest. MATERIALS/METHODS: From June 2008 through June
      2011, 210 patients with HNC receiving RT were randomised to either a control arm
      or humidification using the Fisher & Paykel Healthcare MR880 humidifier. This
      subset analysis involves patients recruited from Auckland City Hospital treated
      with a prescribed dose of >=70 Gy. Regression models included control variables
      for Planning Target Volume 70 GY (PTV70Gy); Equivalent Uniform Dose (EUD) MOIST
      and TSV (surrogates of total mucosal and total swallowing volumes respectively).
      RESULTS: The analysis included 39 patients (humidification 20, control 19). There
      was a significant odds reduction in CTCAE v3.0 functional mucositis score of 0.29
      associated with the use of humidification (p<.001). Within the parameters of the
      model therefore, the risk of a humidification patient being scored as
      experiencing a one-step increase in functional mucositis was 3.45 times lower
      (1/0.29) than for control patients. A control patient was 4.17 times more likely
      to receive an unfavourable nutritional mode score (p<.001). The risk of being
      admitted to hospital decreased by a factor of 11.11 for humidification patients
      (p=.013). CONCLUSION: The results support the hypothesis that humidification can
      help mitigate mucositis symptom burden. Radiotherapy dosimetric parameters assist
      in the evaluation of toxicity interventions.

PMID- 29224828
TI  - Cell-free nucleic acids in body fluids as biomarkers for the prediction and early
      detection of recurrent head and neck cancer: A systematic review of the
      literature.
AB  - Liquid biopsy is a minimally invasive detection method for molecular biomarkers
      in body fluids which may serve as a novel tool in management of head and neck
      cancer. The purpose of this systematic review is to outline the current status of
      liquid biopsy in head and neck squamous cell carcinoma (HNSCC) patients by
      systematically identifying and qualifying all published studies on the diagnostic
      or prognostic value of cell-free nucleic acids detection for posttreatment
      disease monitoring and/or disease outcome. A search was performed in PubMed,
      EMBASE, and Cochrane Library. Thirty articles met the inclusion criteria for
      further analysis. Study and patient characteristics, molecular analysis method
      and treatment or prognostic outcomes were extracted. Seventeen studies
      investigated circulating miRNAs in blood. Of these studies, 16 found
      statistically significant results for a total of 24 different candidate miRNAs
      for prognostication or treatment monitoring. The remaining studies investigated
      circulating tumor DNA by targeting somatic mutations, allelic imbalances,
      hypermethylation, or HPV-DNA. Of these studies, 2 found a statistically
      significant association between nucleic acid levels (tumor DNA targeted by
      allelic imbalances and HPV-DNA) in blood and/or saliva and prognostic outcome.
      One study found significantly different pre- and posttreatment levels of
      mitochondrial DNA in serum. Despite large differences among these studies in both
      design and results, individual results are promising and provide ground for more
      large-scale studies with standardized serial assessment of patient samples in the
      future.

PMID- 29224829
TI  - Plasticity of oral mucosal cell sheets for accelerated and scarless skin wound
      healing.
AB  - OBJECTIVES: Wound healing is generally faster and associated with less scarring
      in the oral mucosa than in the skin. Although rarely studied, oral mucosa
      equivalents may contribute to rapid, scarless cutaneous wound healing. Therefore,
      we examined the potential utility of our newly developed oral mucosal cell sheet
      in skin wound healing. MATERIALS AND METHODS: Oral mucosa and skin samples were
      obtained from surgical patients and Sprague-Dawley rats. Keratinocytes and
      fibroblasts were primarily cultured for in vitro cell expansion. Mucosa and skin
      equivalents were produced with a mixture of cultured fibroblasts and autologous
      fibrin from plasma and seeding keratinocytes. Mucosal and skin cell sheets were
      transplanted in full-thickness excisional wounds of rat skin with control wounds.
      Gross, histological, and molecular characteristics of wound healing according to
      different postsurgical days were compared in control and cell sheet-covered
      wounds. RESULTS: Keratinocytes and fibroblasts derived from the oral mucosa were
      cultured faster than those derived from the skin. The in vitro-engineered oral
      mucosa and skin equivalents were successfully produced using complete autologous
      mucosa or skin and plasma fibrin, showing similarity to the histological
      characteristics of the skin or mucosa. In the in vivo rat model, the oral mucosal
      and skin cell sheet promoted wound healing with early wound closure and less
      scarring. The cell sheet-treated wounds showed lower TGF-beta1, alpha-smooth
      muscle actin, and fibronectin mRNA expression than the control wounds.
      CONCLUSIONS: The oral mucosal cell sheet demonstrated in vivo tissue plasticity
      through good adaptation to skin wounds, contributing to accelerated and scarless
      healing.

PMID- 29224830
TI  - A network meta-analysis in comparing prophylactic treatments of radiotherapy
      induced oral mucositis for patients with head and neck cancers receiving
      radiotherapy.
AB  - OBJECTIVES: The objective of this network meta-analysis is to optimize the
      prophylactic treatment for radiotherapy-induced oral mucositis in patients with
      head and neck cancer (HNSCC) receiving postoperative or definitive radiotherapy
      with or without chemotherapy. MATERIALS AND METHODS: We searched electronic
      databases to identify all eligible randomized clinical trials on oral mucositis.
      The endpoint was grade 0-2 oral mucositis. Odds ratios (OR) and the corresponding
      95% confidence intervals (CI) were extracted. Network meta-analysis was performed
      using the frequentist approach to conduct multiple treatment comparisons.
      RESULTS: In total, 57 trials with 5261 patients were eligible for this study.
      Both direct and network meta-analysis revealed that low-level laser additional to
      standard oral care (SOC) was better than most of the other treatments and
      achieved the highest effect on grade 0-2 oral mucositis, with a surface under the
      cumulative ranking curve (SUCRA) of 95.8%; however, SOC with or without placebo
      had worse effect than most of the other treatments and was ranked worst (SUCRA =
      0.4%). Moreover, sensitivity analysis performed after we had combined the SOC and
      placebo groups (non-medication treatment, NMT) yielded similar results, with
      SUCRA of 91.3% and 3.5% for low-level laser and NMT, respectively. CONCLUSIONS:
      Low-level laser additional to SOC may be a more effective prophylactic treatment
      for reducing severe radiotherapy-induced oral mucositis; SOC alone is
      insufficient for patients with HNSCC receiving postoperative or definitive
      radiotherapy with or without chemotherapy.

PMID- 29224831
TI  - Reconstruction of oral cavity defect using versatile buccinator myomucosal flaps
      in the treatment of cT2-3, N0 oral cavity squamous cell carcinoma: Feasibility,
      morbidity, and functional/oncological outcomes.
AB  - OBJECTIVES: To evaluate the results of oral cavity reconstruction using various
      types of buccinator myomucosal flap (BMMF) for the treatment of cT2-3 oral cavity
      squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: Twenty-two consecutive
      patients who underwent surgical management for OCSCC and reconstruction using
      various types of BMMF were enrolled. Surgical results, complications,
      speech/swallowing outcomes, and recurrence were evaluated. RESULTS: The mean flap
      harvest time was 28.6 min. Complete flap necrosis occurred in one (4.5%) patient
      in whom an island flap was used. There were no other major complications. All
      patients demonstrated normal speech and swallowing functions, with articulation
      correctness >90% and a mean swallowing satisfaction score of 9.6. Occult neck
      lymph node metastasis was found in three (13.6%) patients; however, no recurrence
      at level I was observed. CONCLUSIONS: Reconstruction of the oral cavity using
      various types of BMMF is feasible for treatment of cT2-3 OCSCC, and yields
      favorable outcomes with minimal morbidity.

PMID- 29224832
TI  - The Pathogenesis of Pulmonary Sarcoidosis and Implications for Treatment.
AB  - Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a
      heterogeneous group of patients with a wide range of clinical features and
      associated outcomes. The distinction between isolated thoracic lymphadenopathy
      and pulmonary involvement matters. Morbidity is often higher, and long-term
      outcomes are worse for the latter. Although inflammatory infiltrates in pulmonary
      sarcoidosis may resolve, persistent disease activity is common and can result in
      lung fibrosis. Given the distinct clinical features and natural history of
      pulmonary sarcoidosis, its pathogenesis may differ in important ways from other
      sarcoidosis manifestations. This review highlights recent advances in the
      pathogenesis of pulmonary sarcoidosis, including the nature of the sarcoidosis
      antigen, the role of serum amyloid A and other host factors that contribute to
      alterations in innate immunity, factors that shape adaptive T-cell profiles in
      the lung, and how these mechanisms influence the maintenance of granulomatous
      inflammation in sarcoidosis. We discuss questions raised by recent findings,
      including the role of innate immunity in the pathogenesis, the meaning of immune
      cell exhaustion, and mechanisms that may contribute to lung fibrosis in
      sarcoidosis. We conclude with a reflection on when and how immunosuppressive
      therapies may be helpful for pulmonary sarcoidosis, a consideration of
      nonpharmacologic management strategies, and a survey of potential novel
      therapeutic targets for this vexing disease.

PMID- 29224833
TI  - Hemostasis and Lipoprotein Indices Signify Exacerbated Lung Injury in TB With
      Diabetes Comorbidity.
AB  - BACKGROUND: Exacerbated immunopathology is a frequent consequence of TB that is
      complicated by diabetes mellitus (DM); however, the underlying mechanisms are
      still poorly defined. METHODS: In the two groups of age- and sex-matched patients
      with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated
      the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in
      lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast
      bacilli in sputum smear-positive (SP) patients and compiled CT scan data from
      both the SN and SP patients. We compared inflammatory biomarkers and routine
      hematologic and biochemical parameters. Binary logistic regression analyses were
      applied to define the indices associated with the extent of lung injury. RESULTS:
      Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were
      found in SN patients with DM-TB, consistent with the higher ratio of thick-walled
      cavities and more bacilli in the sputum from SP patients with DM-TB. Larger
      necrotic foci were detected in men compared with women within the SN TB groups.
      Significantly higher fibrinogen and lower high-density lipoprotein cholesterol
      (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed
      that diabetes, activation of the coagulation pathway (shown by increased platelet
      distribution width, decreased mean platelet volume, and shortened prothrombin
      time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol,
      HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN
      and SP patients with TB. CONCLUSIONS: Hemostasis and dyslipidemia are associated
      with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB,
      especially in patients with DM-TB.

PMID- 29224835
TI  - For a better landing.

PMID- 29224836
TI  - Single ventricle i-simulation.

PMID- 29224834
TI  - HDAC1 localizes to the mitochondria of cardiac myocytes and contributes to early
      cardiac reperfusion injury.
AB  - RATIONALE: Recent evidence indicates that histone deacetylase enzymes (HDACs)
      contribute to ischemia reperfusion (I/R) injury, and pan-HDAC inhibitors have
      been shown to be cardioprotective when administered either before an ischemic
      insult or during reperfusion. We have shown previously that selective inhibition
      of class I HDACs provides superior cardioprotection when compared to pan-HDAC
      inhibition in a pretreatment model, but selective class I HDAC inhibition has not
      been tested during reperfusion, and specific targets of class I HDACs in I/R
      injury have not been identified. OBJECTIVE: We hypothesized that selective
      inhibition of class I HDACs with the drug MS-275 (entinostat) during reperfusion
      would improve recovery from I/R injury in the first hour of reperfusion. METHODS
      AND RESULTS: Hearts from male Sprague-Dawley rats were subjected to ex vivo I/R
      injury+/-MS-275 class I HDAC inhibition during reperfusion alone. MS-275
      significantly attenuated I/R injury, as indicated by improved LV function and
      tissue viability at the end of reperfusion. Unexpectedly, we observed that HDAC1
      is present in the mitochondria of cardiac myocytes, but not fibroblasts or
      endothelial cells. We then designed mitochondria-restricted and mitochondria
      excluded HDAC inhibitors, and tested both in our ex vivo I/R model. The selective
      inhibition of mitochondrial HDAC1 attenuated I/R injury to the same extent as MS
      275, whereas the mitochondrial-excluded inhibitor did not. Further assays
      demonstrated that these effects are attributable to a decrease in SDHA activity
      and subsequent metabolic ROS production in reperfusion. CONCLUSIONS: We
      demonstrate for the first time that HDAC1 is present within the mitochondria of
      cardiac myocytes, and mitochondrial HDAC1 contributes significantly to I/R injury
      within the first hour of reperfusion.

PMID- 29224837
TI  - Keep it simple: Repair of atrioventricular valve regurgitation in patients with a
      single ventricle.

PMID- 29224838
TI  - Aortic coarctation decision making comes of age.

PMID- 29224840
TI  - Discussion.

PMID- 29224839
TI  - Intraoperative costs of video-assisted thoracoscopic lobectomy can be
      dramatically reduced without compromising outcomes.
AB  - OBJECTIVE: To determine whether surgeon selection of instrumentation and other
      supplies during video-assisted thoracoscopic lobectomy (VATSL) can safely reduce
      intraoperative costs. METHODS: In this retrospective, cost-focused review of all
      video-assisted thoracoscopic surgery anatomic lung resections performed by 2
      surgeons at a single institution between 2010 and 2014, we compared VATSL
      hospital costs and perioperative outcomes between the surgeons, as well as costs
      of VATSL compared with thoracotomy lobectomy (THORL). RESULTS: A total of 100
      VATSLs were performed by surgeon A, and 70 were performed by surgeon B. The
      preoperative risk factors did not differ significantly between the 2 groups of
      surgeries. Mean VATSL total hospital costs per case were 24% percent greater for
      surgeon A compared with surgeon B (P = .0026). Intraoperative supply costs
      accounted for most of this cost difference and were 85% greater for surgeon A
      compared with surgeon B (P < .0001). The use of nonstapler supplies, including
      energy devices, sealants, and disposables, drove intraoperative costs, accounting
      for 55% of the difference in intraoperative supply costs between the surgeons.
      Operative time was 25% longer for surgeon A compared with surgeon B (P < .0001),
      but this accounted for only 11% of the difference in total cost. Surgeon A's
      overall VATSL costs per case were similar to those of THORLs (n = 100) performed
      over the same time period, whereas surgeon B's VATSL costs per case were 24% less
      than those of THORLs. On adjusted analysis, there was no difference in VATSL
      perioperative outcomes between the 2 surgeons. CONCLUSIONS: The costs of VATSL
      differ substantially among surgeons and are heavily influenced by the use of
      disposable equipment/devices. Surgeons can substantially reduce the costs of
      VATSL to far lower than those of THORL without compromising surgical outcomes
      through prudent use of costly instruments and technologies.

PMID- 29224841
TI  - Metal ion-improved complexation countercurrent chromatography for
      enantioseparation of dihydroflavone enantiomers.
AB  - Cu(II) ion was selected as an additive to improve the enantioseparation
      efficiency of three dihydroflavone enantiomers in high-speed counter-current
      chromatography (HSCCC), using hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) as
      the chiral selector. The influences of important parameters, including the metal
      ion, the concentrations of HP-beta-CyD and the Cu(II) ion, and the sample size
      were investigated. Under optimal conditions, three dihydroflavone enantiomers,
      including (+/-)-hesperetin, (+/-)-naringenin, and (+/-)-farrerol, were
      successfully enantioseparated. The chiral recognition mechanism was investigated.
      The enantioseparation was attributed to the different thermodynamic stabilities
      of the binary complexes of HP-beta-CyD and (+/-)-hesperetin, and Cu(II) ion could
      enhance this difference by forming ternary complexes with the binary complexes.
      This Cu(II) ion-improved complexation HSCCC system exhibited improved performance
      for chiral separation, and therefore it has great application potential in the
      preparative enantioseparation of other compounds with similar skeletons.

PMID- 29224842
TI  - M13 bacteriophage purification using poly(ionic liquids) as alternative
      separation matrices.
AB  - M13 is a filamentous, non-lytic bacteriophage that infects Escherichia coli via
      the F pilus. Currently, phage M13 is widely used in phage display technology and
      bio-nanotechnology, and is considered a possible antibacterial therapeutic agent,
      among other applications. Conventional phage purification involves 5-7
      operational steps, with high operational costs and significant product loss
      (approximately 60%). In this work, we propose a scalable purification process for
      M13 bacteriophage using a novel stationary phase based on a polymeric ionic
      liquid (PIL) with a positively charged backbone structure. Poly (1-vinyl-3-ethyl
      imidazolium bis(trifluoromethylsulfonyl) imide) - poly(VEIM-TFSI) predominantly
      acted as an anion exchanger under binding-elution mode. This revealed to be a
      rapid and simple method for the recovery of phage M13 with an overall separation
      yield of over 70% after a single downstream step. To the best of our knowledge,
      PILs have never been used as separation matrices for biological products and the
      results obtained, together with the large number of cations and anions available
      to prepare PILs, illustrate well the large potential of the proposed methodology.

PMID- 29224843
TI  - Evaluation of the impact of preoperative education in ambulatory laparoscopic
      cholecystectomy. A prospective, double-blind randomized trial.
AB  - INTRODUCTION: Outpatient laparoscopic cholecystectomy is a safe procedure and
      provides a better use of health resources and perceived satisfaction without
      affecting quality of care. Preoperative education has shown less postoperative
      stress, pain and nausea in some interventions. The principal objective of this
      study is to assess the impact of preoperative education on postoperative pain in
      patients undergoing ambulatory laparoscopic cholecystectomy. Secondary objectives
      were: to evaluate presence of nausea, morbidity, hospital admissions,
      readmissions rate, quality of life and satisfaction. METHODS: Prospective,
      randomized, and double blind study. Between April 2014 and May 2016, 62 patients
      underwent outpatient laparoscopic cholecystectomy. INCLUSION CRITERIA: ASA I-II,
      age 18-75, outpatient surgery criteria, abdominal ultrasonography with
      cholelithiasis. Patient randomization in two groups, group A: intensified
      preoperative education and group B: control. RESULTS: Sixty-two patients
      included, 44 women (71%), 18 men (29%), mean age 46,8 years (20-69). Mean BMI
      27,5. Outpatient rate 92%. Five cases required admission, two due to nausea. Pain
      scores obtained using a VAS was at 24-hour, 2,9 in group A and 2,7 in group B.
      There were no severe complications or readmissions. Results of satisfaction and
      quality of life scores were similar for both groups. CONCLUSIONS: We did not find
      differences due to intensive preoperative education. However, we think that a
      correct information protocol should be integrated into the patient's preoperative
      preparation. Registered in ISRCTN number ISRCTN83787412.

PMID- 29224844
TI  - Social management of laboratory rhesus macaques housed in large groups using a
      network approach: A review.
AB  - Biomedical facilities across the nation and worldwide aim to develop cost
      effective methods for the reproductive management of macaque breeding groups,
      typically by housing macaques in large, multi-male multi-female social groups
      that provide monkey subjects for research as well as appropriate socialization
      for their psychological well-being. One of the most difficult problems in
      managing socially housed macaques is their propensity for deleterious aggression.
      From a management perspective, deleterious aggression (as opposed to less intense
      aggression that serves to regulate social relationships) is undoubtedly the most
      problematic behavior observed in group-housed macaques, which can readily
      escalate to the degree that it causes social instability, increases serious
      physical trauma leading to group dissolution, and reduces psychological well
      being. Thus for both welfare and other management reasons, aggression among
      rhesus macaques at primate centers and facilities needs to be addressed with a
      more proactive approach.Management strategies need to be instituted that maximize
      social housing while also reducing problematic social aggression due to
      instability using efficacious methods for detection and prevention in the most
      cost effective manner. Herein we review a new proactive approach using social
      network analysis to assess and predict deleterious aggression in macaque groups.
      We discovered three major pathways leading to instability, such as unusually high
      rates and severity of trauma and social relocations.These pathways are linked
      either directly or indirectly to network structure in rhesus macaque societies.
      We define these pathways according to the key intrinsic and extrinsic variables
      (e.g., demographic, genetic or social factors) that influence network and
      behavioral measures of stability (see Fig. 1). They are: (1) presence of natal
      males, (2) matrilineal genetic fragmentation, and (3) the power structure and
      conflict policing behavior supported by this power structure. We discuss how
      these three major pathways leading to greater understanding and predictability of
      deleterious aggression in macaque social groups.

PMID- 29224845
TI  - Expanding roles for the Tbet+ B cell subset in health and disease.

PMID- 29224846
TI  - Laparoscopic sentinel node detection with ICG for early ovarian cancer:
      Description of a technique and literature review.

PMID- 29224847
TI  - Familial deep endometriosis: A rare monogenic disease?
AB  - Endometriosis is a frequent cause of pelvic pain and subfertility in women of
      reproductive age. Presence of extra-uterine endometrial-like tissue is
      responsible for non-specific symptoms such as chronic pelvic pain, dysmenorrhea,
      dyspareunia, dyschesia and sometimes infertility. Three different phenotypes
      according to the location of the lesions are described, namely peritoneal,
      ovarian and deep infiltrating endometriosis. Deep endometriosis is considered as
      a distinct homogeneous disease. Heritability of endometriosis has been previously
      demonstrated. Despite extensive efforts to characterize candidate alleles
      contributing to genetic basis of endometriosis, these factors relevant to
      endometriosis pathophysiology remain unclear. No high penetrance pathogenic
      variant could be identified. We report herein two families with familial
      aggregation of severe deep infiltrating endometriosis, providing further evidence
      for monogenic mendelian inheritance of this form of endometriosis.

PMID- 29224848
TI  - Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss
      using second-generation enzyme immunoassay: A retrospective, multi-institutional
      investigation in Hokkaido, Japan.
AB  - OBJECTIVE: Although elevated anti-mumps IgM antibody levels were reported in 5.7%
      7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there
      were several reports of false-positive cases, such as the continually IgM
      positive case and the IgM positive case in normal adults. To improve specificity,
      the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was
      introduced in December 2009. This study re-examined the frequency of anti-mumps
      IgM antibody test positivity with SSNHL using the new measurement kit and
      compared the results with those from a previous report that used old kit.
      METHODS: This is a retrospective multi-institutional study involving patients
      diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the
      positive rate of anti-mumps IgM antibody and the annual average number of mumps
      cases per sentinel in Hokkaido between the patients in the present study and
      patients previously evaluated. RESULTS: Overall, 100 patients with SSNHL were
      enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69
      patients evaluated in the previous study, 5 cases (7.2%) were positive for anti
      mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the
      present cases was significantly lower than that previously reported (p=0.042).
      The annual average number of mumps cases per sentinel in Hokkaido of the present
      and previous surveillance period was 34.47 and 42.77, respectively; no
      significant difference was seen in these data (p=0.4519). CONCLUSION: The present
      study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody
      using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM
      measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly
      decreased, indicating that the proportion of asymptomatic mumps among etiology of
      SSNHL may be lower than those previously reported.

PMID- 29224849
TI  - Aptamers as potential therapeutic agents for ovarian cancer.
AB  - Current therapy for ovarian cancer typically involves indiscriminate
      chemotherapies that can have severe off target effects on healthy tissue and are
      still plagued by aggressive recurrence. Recent shifts towards targeted therapies
      offer the possibility of circumventing the obstacles experienced by these
      traditional treatments. While antibodies are the pioneering agents in targeted
      therapies, clinical experience has demonstrated that their antitumor efficacy is
      limited due to their high immunogenicity, large molecular size, and costly and
      laborious production. In contrast, nucleic acid based chemical antibodies, also
      known as aptamers, are ideal for this application given their small size, lack of
      immunogenicity and in vitro production. As aptamers have begun to demonstrate
      their promise through targeting Epithelial Cell Adhesion Molecule (EpCAM), as
      well as a number of ovarian cancer biomarkers, in in vivo and in vitro models,
      their clinical applicability is slowly being realised. This review explores some
      of the current progress of aptamers targeting cancer biomarkers and their
      potential role as ovarian cancer therapeutics.

PMID- 29224850
TI  - The minimal ESCRT machinery of Giardia lamblia has altered inter-subunit
      interactions within the ESCRT-II and ESCRT-III complexes.
AB  - The ESCRT pathway functions at different subcellular membranes to induce their
      negative curvature, and it has been largely characterized in model eukaryotes
      belonging to Opisthokonta. But searches of the genomes of many nonopisthokonts
      belonging to various supergroups indicate that some of them may harbour fewer
      ESCRT components. Of the genomes explored thus far, one of the most minimal set
      of ESCRT components was identified in the human pathogen Giardia lamblia, which
      belongs to Excavata. Here we report that an ESCRT-mediated pathway most likely
      operates at the peripheral vesicles, which are located at the cell periphery and
      the bare zone of this protist. Functional comparison of all the identified
      putative giardial ESCRT components, with the corresponding well-characterized
      orthologues from Saccharomyces cerevisiae, indicated that only some of the ESCRT
      components could functionally substitute for the corresponding yeast proteins.
      While GlVps25, GlVps2, and all three paralogues of GlVps4, tested positive in
      functional complementation assays, GlVps22, GlVps20, and GlVps24 did not. Binary
      interactions of either GlVps22 or GlVps25, with other ESCRT-II components from
      Giardia or yeast indicate that the giardial Vps36 orthologue is either completely
      missing or highly diverged. Interactions within the giardial ESCRT-III components
      also differ from those in yeast; while GlVps46a interacts preferentially with
      Vps24 compared to Vps2, GlVps46b, like the yeast orthologue, interacts with both.

PMID- 29224851
TI  - The effects of exercise on depressive- and anxiety-like behaviors as well as lung
      and hippocampus oxidative stress in ovalbumin-sensitized juvenile rats.
AB  - Allergic asthma during early life period has been reported to be associated with
      neurochemical and behavioral disorders, including anxiety and depression. We
      aimed to determine the effects of exercise on depressive- and anxiety-like
      behaviors as well as lung and hippocampus oxidative stress in ovalbumin (OVA)
      sensitized juvenile rats. Animals were divided into 4 groups including control
      (non-exercised and non-sensitized), Exe (exercise and non-sensitized); OVA (non
      exercised and OVA-sensitized); and OVA+Exe (exercised and OVA-sensitized). The
      rats were subjected to chronic OVA sensitization followed by 4 weeks of treadmill
      exercise training. Compared to the control group, the OVA group had an increase
      in anxiety- and depressive-like behavior, lung inflammation, and oxidative stress
      index in the lung and hippocampus. Compared to the OVA group, the OVA+Exe group
      had a decline in anxiety- and depressive-like behavior, lung inflammation, and
      oxidative stress index in the lung and hippocampus. No significant difference in
      terms of the above-mentioned parameters, were found between the control group and
      the Exe group. Exercise decreased depressive- and anxiety-like behaviors in OVA
      sensitized juvenile rats; this effect might have been mainly mediated by
      improvement in antioxidant system.

PMID- 29224852
TI  - Structured Spontaneity: Building Circuits in the Human Prenatal Brain.
AB  - Early brain activity is crucial for neurogenesis and the development of brain
      networks. However, it has been challenging to localize regions in the developing
      human brain that contribute to spontaneous waves of neuronal activity. Recently,
      Arichi and colleagues reported that the temporal and heteromodal insular cortices
      have a central role in propagating these neural instructional signals.

PMID- 29224853
TI  - Adaptive sliding mode control for finite-time stability of quad-rotor UAVs with
      parametric uncertainties.
AB  - Adaptive control methods are developed for stability and tracking control of
      flight systems in the presence of parametric uncertainties. This paper offers a
      design technique of adaptive sliding mode control (ASMC) for finite-time
      stabilization of unmanned aerial vehicle (UAV) systems with parametric
      uncertainties. Applying the Lyapunov stability concept and finite-time
      convergence idea, the recommended control method guarantees that the states of
      the quad-rotor UAV are converged to the origin with a finite-time convergence
      rate. Furthermore, an adaptive-tuning scheme is advised to guesstimate the
      unknown parameters of the quad-rotor UAV at any moment. Finally, simulation
      results are presented to exhibit the helpfulness of the offered technique
      compared to the previous methods.

PMID- 29224855
TI  - Finding representative electrocardiogram beat morphologies with CUR.
AB  - In this paper, we use the CUR matrix factorization as a means of dimension
      reduction to identify important subsequences in electrocardiogram (ECG) time
      series. As opposed to other factorizations typically used in dimension reduction
      that characterize data in terms of abstract representatives (for example, an
      orthogonal basis), the CUR factorization describes the data in terms of actual
      instances within the original data set. Therefore, the CUR characterization can
      be directly related back to the clinical setting. We apply CUR to a synthetic ECG
      data set as well as to data from the MIT-BIH Arrhythmia, MGH-MF, and Incart
      databases using the discrete empirical interpolation method (DEIM) and an
      incremental QR factorization. In doing so, we demonstrate that CUR is able to
      identify beat morphologies that are representative of the data set, including
      rare-occurring beat events, providing a robust summarization of the ECG data. We
      also see that using CUR-selected beats to label the remaining unselected beats
      via 1-nearest neighbor classification produces results comparable to those
      presented in other works. While the electrocardiogram is of particular interest
      here, this work demonstrates the utility of CUR in detecting representative
      subsequences in quasiperiodic physiological time series.

PMID- 29224856
TI  - Controlled searching in reversibly de-identified medical imaging archives.
AB  - Nowadays, digital medical imaging in healthcare has become a fundamental tool for
      medical diagnosis. This growth has been accompanied by the development of
      technologies and standards, such as the DICOM standard and PACS. This environment
      led to the creation of collaborative projects where there is a need to share
      medical data between different institutions for research and educational
      purposes. In this context, it is necessary to maintain patient data privacy and
      provide an easy and secure mechanism for authorized personnel access. This paper
      presents a solution that fully de-identifies standard medical imaging objects,
      including metadata and pixel data, providing at the same time a reversible de
      identifier mechanism that retains search capabilities from the original data. The
      last feature is important in some scenarios, for instance, in collaborative
      platforms where data is anonymized when shared with the community but searchable
      for data custodians or authorized entities. The solution was integrated into an
      open source PACS archive and validated in a multidisciplinary collaborative
      scenario.

PMID- 29224854
TI  - Encephalitis in US Children.
AB  - Encephalitis is an uncommon but severe disease characterized by neurologic
      dysfunction with central nervous system inflammation. Children with encephalitis
      should receive supportive care and empiric therapies for common and treatable
      causes while prioritizing diagnostic evaluation for common, treatable, and high
      risk conditions. Even with an extensive diagnostic workup, an infectious cause is
      identified in less than half of cases, suggesting a role for postinfectious or
      noninfectious processes.

PMID- 29224857
TI  - Nutritional depletion of total mixed rations by European starlings: Projected
      effects on dairy cow performance and potential intervention strategies to
      mitigate damage.
AB  - European starlings are an invasive bird species in North America that are known
      to cause damage to commercial dairies through the consumption of total mixed
      rations (TMR) destined for dairy cows. We hypothesized that large foraging flocks
      of starlings alter the physical composition of TMR, and that this change may be
      significant enough to affect milk production. To better determine if production
      losses could potentially occur in commercial dairies as a consequence of feed
      consumption by foraging flocks of starlings, we conducted controlled feeding
      experiments using a TMR sourced from a commercial dairy that is chronically
      plagued with seasonal starling damage. European starlings selected the high
      energy fraction of the TMR and reduced starch and crude fat availability. Using
      the dairy National Research Council production model equations, the nutritional
      changes measured in the controlled feeding experiments could potentially reduce
      the productivity of dairies. Model output suggests that for Holsteins producing
      32 kg of milk/d, total required net energy intake (NEI) was 31.5 Mcal/d. Within
      the reference TMR, NEI supplied was 29.3 Mcal/d, whereas within the starling
      consumed TMR NEI supplied was 27.7 Mcal/d. Following our nutrition experiments,
      we assessed the efficacy of pelleted feed as a deterrent strategy for bird damage
      management in commercial dairies. Six different pelleted feed treatments of
      differing diameter were offered to starlings. All pellets of 0.95 cm diameter or
      larger inhibited starling consumption by >=79%.

PMID- 29224858
TI  - A resynchronization of ovulation program based on ovarian structures present at
      nonpregnancy diagnosis reduced time to pregnancy in lactating dairy cows.
AB  - Our objective was to evaluate time to pregnancy after the first service
      postpartum and pregnancy per artificial insemination (P/AI) in dairy cows managed
      with 2 resynchronization of ovulation programs. After first service, lactating
      Holstein cows were blocked by parity (primiparous vs. multiparous) and randomly
      assigned to the d 32 Resynch (R32; n = 1,010) or short Resynch (SR; n = 1,000)
      treatments. Nonpregnancy diagnosis (NPD) was conducted 32 +/- 3 d after AI by
      transrectal ultrasonography. Nonpregnant cows in R32 received the Ovsynch
      protocol: GnRH, PGF2alpha 7 d later, GnRH 56 h later, and timed AI (TAI) 16 to 18
      h later. Cows in SR with a corpus luteum (CL) >=15 mm and a follicle >=10 mm at
      NPD received PGF2alpha, PGF2alpha 24 h later, GnRH 32 h later, and TAI 16 to 18 h
      later. Cows in SR without a CL >=15 mm or a follicle >=10 mm at NPD received a
      modified Ovsynch protocol with 2 PGF2alpha treatments and progesterone (P4)
      supplementation (GnRH plus CIDR, PGF2alpha and CIDR removal 7 d later, PGF2alpha
      24 h later, GnRH 32 h later, and TAI 16 to 18 h later). Blood samples were
      collected from a subgroup of cows at the GnRH before TAI (R32 = 114; SR = 121) to
      measure P4 concentration. Binomial outcomes were analyzed with logistic
      regression and hazard of pregnancy (R32 = 485; SR = 462) with Cox's proportional
      regression in SAS (SAS Institute, Cary, NC). For P/AI analysis, the TAI service
      was the experimental unit (R32 = 720; SR = 819). Models included treatment and
      parity as fixed effects and farm as random effect. The hazard of pregnancy was
      greater for the SR treatment (hazard ratio = 1.18; 95% confidence interval: 1.01
      1.37). Median time to pregnancy was 95 and 79 d for the R32 and SR treatments,
      respectively. At NPD, 71.3 and 71.2% of cows had a CL for the R32 and SR
      treatments, respectively. Treatment did not affect overall P/AI 32 +/- 3 d after
      AI (R32 = 31.0% vs. SR = 33.9%) or for cows with a CL at NPD (R32 = 32.7% vs. SR
      = 32.8%). For cows with no CL at NPD, P/AI was greater for the SR treatment
      (36.9%) than for the R32 treatment (28.6%). Pregnancy loss from 32 to 63 d after
      AI was similar for all services combined (R32 = 8.3% vs. SR = 10.4%) and for cows
      with no CL at NPD (R32 = 13.2% vs. SR = 7.2%) but tended to be affected by
      treatment for cows with a CL at NPD (R32 = 6.8% vs. SR = 11.9%). Treatment
      affected the proportion of cows with P4 <=0.5 ng/mL at the GnRH before TAI for
      all cows (R32 = 68.4% vs. SR = 81.8%), tended to have an effect among cows with a
      CL (R32 = 70.0% vs. SR = 81.8%), and had no effect for cows with no CL (R32 =
      64.7% vs. SR = 81.8%). We concluded that the SR program reduced time to pregnancy
      because of a reduction of the interbreeding interval for cows with a CL at NPD
      and greater P/AI in cows with no CL at NPD.

PMID- 29224859
TI  - Effects of rumen-degradable protein:rumen-undegradable protein ratio and corn
      processing on production performance, nitrogen efficiency, and feeding behavior
      of Holstein dairy cows.
AB  - This study was conducted to investigate the effects of the ratio of rumen
      degradable protein (RDP) to rumen-undegradable protein (RUP) and corn processing
      method on production performance, nitrogen (N) efficiency, and feeding behavior
      of high-producing Holstein dairy cows. Twelve multiparous Holstein cows (second
      parity; milk yield = 48 +/- 3 kg/d) were assigned to a replicated 4 * 4 Latin
      square design with a 2 * 2 factorial arrangement of treatments. Factor 1 was corn
      processing method [ground corn (GC) or steam flaked corn (SFC) with a flake
      density of about 390 g/L], and factor 2 was RDP:RUP ratio [low ratio (LR) =
      60:40; high ratio (HR) = 65:35] based on crude protein (%). The crude protein
      concentrations were kept constant across the treatments (16.7% of DM). No
      significant interactions of main treatment effects occurred for lactation
      performance data. Cows fed 2 different RDP:RUP ratios exhibited similar dry
      matter intake (DMI), but those fed SFC showed decreased feed intake compared with
      those receiving GC (25.1 +/- 0.48 vs. 26.2 +/- 0.47 kg/d, respectively). Cows fed
      HR diets produced more milk than did those fed LR diets (44.4 +/- 1.05 vs. 43.2
      +/- 1.05 kg/d, respectively). Milk fat content decreased but milk protein content
      increased in cows fed SFC compared with those fed GC. Feed efficiency (i.e., milk
      yield/DMI) was enhanced with increasing ratio of RDP:RUP (1.68 +/- 0.04 vs. 1.74
      +/- 0.04 for LR and HR, respectively). Apparent N efficiency was higher in cows
      fed HR than in those fed LR (30.4 +/- 0.61 vs. 29.2 +/- 0.62, respectively).
      Compared with cows fed the GC-based diet, those receiving SFC exhibited lower
      values of N intake, N-NH3 concentration, and fecal N excretion. Cows receiving
      SFC-based diets spent more time ruminating (min/kg of DMI) than did those fed GC.
      Although these results showed no interaction effects of RDP:RUP ratio and corn
      processing method on performance, higher RDP:RUP ratios and ground corn can be
      effective feeding strategies for feed to lactating cows receiving high
      concentrate diets.

PMID- 29224860
TI  - Estrous detection intensity and accuracy and optimal timing of insemination with
      automated activity monitors for dairy cows.
AB  - The objectives of this observational study were to assess the ability of
      automated activity monitoring (AAM) to detect estrus for first insemination, the
      accuracy of detection, and the optimum interval from the estrus alert from the
      AAM system to insemination. Four commercial farms using 1 of 2 commercial AAM
      systems were studied over 1 yr. Cows were inseminated between 55 and 80 d in milk
      (DIM) based on AAM only, then by a combination of AAM and timed artificial
      insemination (AI). Blood progesterone was measured in 1,014 cows at wk 5, 7, and
      9 postpartum; purulent vaginal discharge (PVD) was assessed at wk 5; and lameness
      and BCS at wk 7. Overall, AAM detected 83% of cows in estrus by 80 DIM. Cows that
      had 3 serum progesterone <1 ng/mL, had PVD, or were both lame and had BCS <=2.5
      has lesser odds of being detected in estrus by 80 DIM (62, 68, and 53%,
      respectively). Blood samples were collected on the day of 445 AI based on AAM and
      323 timed AI. The proportion of cows not in estrus (progesterone >1 ng/mL) on the
      day of AI was similar between AAM (4 +/- 1.8%) and timed AI (3 +/- 1.2%).
      Managers elected, based on subjective criteria, not to inseminate 17% of cows for
      which an AAM estrus alert was issued, of which 43% were not in estrus. Activity
      data were extracted from AAM software for 1,399 AI. Onset of estrus was
      calculated using the same or similar data processing criteria as the AAM system.
      Producers recorded the time of AI. The interval from onset of estrus to AI was
      categorized as 0 to 8, 8 to 16, or 16 to 24 h. We found no effect of AAM system
      on the probability of pregnancy per AI, but noted an interaction of interval with
      parity. For multiparous cows, the probability of pregnancy per AI was 31%, which
      did not differ with the interval to AI. For primiparous cows, the odds of
      pregnancy were greater if AI occurred 0 to 8 h (49%) than 8 to 16 (36%) or 16 to
      24 h (31%) after the estrus alert from the AAM. Automated activity monitoring can
      detect estrus for first AI in just over the length of 1 estrous cycle for over
      80% of cows, but the remainder would likely require intervention for timely
      insemination. For multiparous cows, performing AI based on AAM once per day would
      not affect pregnancy per AI, but for primiparous cows AI within 8 h of the onset
      of estrus may be advantageous.

PMID- 29224861
TI  - A survey of selected animal-based measures of dairy cattle welfare in the Eastern
      Alps: Toward context-based thresholds.
AB  - In the Alps, traditional dairy farms are small-scale operations where vertical
      transhumance from valley indoor housing systems to highland pasture-based systems
      is still practiced in summer. Vertical transhumance implies a substantial change
      of environment, available resources, and management practices from one season to
      another. In such systems, animal-based welfare measures need to be monitored
      throughout the year to capture the variation of welfare outcomes, based on which
      targeted welfare management plans can be implemented. Because the Welfare Quality
      assessment approach has been tailored to indoor housing and intensive farming
      systems, the European Food Safety Authority recently developed a welfare
      assessment protocol for small-scale dairy cattle farms adapted after the Welfare
      Quality framework. The aim of this study was to assess nonbehavioral animal-based
      measures as defined by this protocol at different time points for transhumant
      systems in the Alps. In total, 18 animal-based measures were assessed before,
      during, and after the mountain pasture period in a sample of 67 small-scale dairy
      cattle farms practicing vertical transhumance in neighboring provinces of
      Austria, Italy, and Slovenia. Significant differences between assessments were
      identified for dirtiness of legs and teats, hairless patches, lesions and
      swellings, claw condition, ocular discharge, and diarrhea whereas BCS,
      lameness/severe lameness, vulvar discharge, nasal discharge, and hampered
      respiration were unchanged between seasons. In addition, a benchmarking exercise
      was carried out to identify relative boundaries (worst quartile thresholds) for
      each animal-based measure and to contribute to the discussion about achievable
      welfare outcomes for the 2 husbandry conditions that characterize a transhumant
      system. Worst quartile thresholds indicated a high prevalence of dirtiness (>80%)
      when cows were kept indoors, high prevalence of hairless patches (65%) before
      pasture turnout, and high prevalence of very lean cows (>13%) throughout the
      assessments. On the other hand, the best quartile thresholds for most clinical
      conditions suggested that high welfare standards (zero prevalence) are widely
      achievable in mountain farms practicing vertical transhumance during all
      assessments. The thresholds identified through benchmarking should serve as the
      basis for an effective context-based welfare management strategy promoting
      continuous welfare improvement on-farm.

PMID- 29224862
TI  - In vitro investigation of anticancer, antihypertensive, antidiabetic, and
      antioxidant activities of camel milk fermented with camel milk probiotic: A
      comparative study with fermented bovine milk.
AB  - This study aimed to investigate in vitro anticancer activity by antiproliferative
      activity, antihypertensive activity by angiotensin-converting enzyme inhibition,
      antidiabetic activity by alpha-amylase and alpha-glucosidase inhibitions, and
      antioxidant activities of camel milk fermented with camel milk probiotic compared
      with fermented bovine milk. The camel milk probiotic strain Lactococcus lactis
      KX881782 (Lc.K782) and control Lactobacillus acidophilus DSM9126 (La.DSM) were
      used to prepare fermented camel and bovine milks separately. The proteolytic
      activities of water-soluble extract (WSE) in all fermented camel milk were higher
      than those in fermented bovine milk. The alpha-glucosidase inhibitions in both
      milk types fermented by Lc.K782 ranged from 30 to 40%. Camel milk fermented by
      Lc.K782 had the highest antioxidant activity by 2,2'-azino-bis(3-ethylbenzo
      thiazoline-6-sulphonic acid). The highest angiotensin-converting enzyme
      inhibition of WSE in camel milk fermented by Lc.K782 was >80%. The proliferations
      of Caco-2, MCF-7, and HELA cells were more inhibited when treated with WSE of
      fermented camel milk extracts.

PMID- 29224863
TI  - Quantifying fecal shedding of Mycobacterium avium ssp. paratuberculosis from
      calves after experimental infection and exposure.
AB  - Johne's disease, a chronic enteritis caused by Mycobacterium avium ssp.
      paratuberculosis (MAP), causes large economic losses to the dairy industry
      worldwide. Fecal shedding of MAP contaminates the environment, feed, and water
      and contributes to new infections on farm, yet there is limited knowledge
      regarding mechanisms of shedding, extent of intermittent shedding, and numbers of
      MAP bacteria shed. The objectives were to (1) compare (in an experimental
      setting) the frequency at which intermittent shedding occurred and the quantity
      of MAP shed among pen mates that were inoculated or contact-exposed (CE); and (2)
      determine whether an association existed between inoculation dose and quantity of
      MAP shed. In the first experiment, 32 newborn Holstein-Friesian bull calves were
      allocated to pens in groups of 4, whereby 2 calves were inoculated with a
      moderate dose (MD; 5 * 108 cfu) of MAP and 2 calves acted as CE. Calves were
      group-housed for 3 mo, fecal samples were collected and cultured, and culture
      positive samples were quantified. In the second experiment, 6 calves were
      inoculated with either a low (LD) or high (HD) dose of MAP (1 * 108 or 1 * 1010
      cfu, respectively), and fecal samples were collected for 3 mo and cultured for
      detection of MAP. The amount of MAP was quantified using direct extraction (DE)
      of DNA from fecal samples and F57-specific quantitative PCR. In experiment 1, the
      average amount of MAP in all culture-positive samples did not differ between MD
      and CE calves. In experiment 2, when comparing inoculation doses, LD calves had
      the lowest proportion of MAP-positive culture samples and HD had the highest, but
      no difference was detected in the average quantity of MAP shed. This study
      provided new information in regards to Johne's disease research and control
      regarding shedding from various inoculation doses and from CE animals; these data
      should inform future trials and control programs.

PMID- 29224864
TI  - Symposium review: Breeding a better cow-Will she be adaptable?
AB  - Adaption is a process that makes an individual or population more suited to their
      environment. Long-term adaptation is predicated on ample usable genetic
      variation. Evolutionary forces influencing the extent and dynamics of genetic
      variation in a population include random drift, mutation, recombination,
      selection, and migration; the relative importance of each differs by population
      (i.e., drift is likely to be more influential in smaller populations) and number
      of generations exposed to selection (i.e., mutation is expected to contribute
      substantially to genetic variability following many generations of selection).
      The infinitesimal model, which underpins most genetic and genomic evaluations,
      assumes that each quantitative trait is controlled by an infinitely large number
      of unlinked and non-epistatic loci, each with an infinitely small effect. Under
      the infinitesimal model, selection is not expected to noticeably alter the allele
      frequencies, despite a potential substantial change in the population mean; the
      exception is in the first few generations of selection when genetic variance is
      expected to decline, after which it stabilizes. Despite the common use of the
      heritability statistic in quantitative genetics as a descriptor of adaption or
      response to selection, it is arguably the coefficient of genetic variation that
      is more informative to gauge adaptation potential and should, therefore, always
      be cited in such studies; for example, the heritability of fertility traits in
      dairy cows is generally low, yet the coefficient of genetic variation for most
      traits is comparable to many other performance traits, thus supporting the
      observed rapid genetic gain in fertility performance in dairy populations.
      Empirical evidence from long-term selection studies, across a range of animal and
      plant species, fails to support the premise that selection will deplete genetic
      variability. Even after 100 yr (synonymous with 100 generations) of selection in
      corn for high protein or oil content, there appears to be no obvious plateauing
      in the response to selection. Although populations in several selection
      experiments did reach a selection limit after multiple generations of directional
      selection, this does not equate to an exhaustion of genetic variance; such a
      declaration is supported by the observed rapid responses to reverse selection
      once implemented in long-term selection studies. New technologies such as genome
      wide enabled selection and genome editing, as well as having the potential to
      accelerate genetic gain, could also increase the genetic variation, or at least
      reduce the erosion of genetic variance over time. In conclusion, there is no
      evidence, either theoretical or empirical, to indicate that dairy cow breeding
      programs will be unable to adapt to evolving challenges and opportunities, at
      least not because of an absence of ample genetic variability.

PMID- 29224865
TI  - Effects of supplementation with ruminally protected choline on performance of
      multiparous Holstein cows did not depend upon prepartum caloric intake.
AB  - Objectives were to evaluate the effect of prepartum energy intake on performance
      of dairy cows supplemented with or without ruminally protected choline (RPC; 0 or
      17.3 g/d of choline chloride; 0 or 60 g/d of ReaShure, Balchem Corp., New
      Hampton, NY). At 47 +/- 6 d before the expected calving date, 93 multiparous
      Holstein cows were assigned randomly to 1 of 4 dietary treatments in a 2 * 2
      factorial arrangement. Cows were fed energy to excess [EXE; 1.63 Mcal of net
      energy for lactation/kg of dry matter (DM)] or to maintenance (MNE; 1.40 Mcal of
      net energy for lactation/kg of DM) in ad libitum amounts throughout the
      nonlactating period. The RPC was top-dressed for 17 +/- 4.6 d prepartum through
      21 d postpartum (PP). After calving, cows were fed the same methionine-balanced
      diet, apart from RPC supplementation, through 15 wk PP. Liver was biopsied at 
      14, 7, 14, and 21 d relative to parturition. Cows fed EXE or MNE diets,
      respectively, consumed 40 or 10% more Mcal/d than required at 15 d before
      parturition. Cows fed the MNE compared with the EXE diet prepartum consumed 1.2
      kg/d more DM postpartum but did not produce more milk (41.6 vs. 43.1 kg/d). Thus,
      PP cows fed the EXE diet prepartum were in greater mean negative energy balance,
      tended to have greater mean concentrations of circulating insulin, fatty acids,
      and beta-hydroxybutyrate, and had greater triacylglycerol in liver tissue (8.3
      vs. 10.7% of DM) compared with cows fed the MNE diet prepartum. Cows fed RPC in
      transition tended to produce more milk (43.5 vs. 41.3 kg/d) and energy-corrected
      milk (44.2 vs. 42.0 kg/d) without increasing DM intake (23.8 vs. 23.2 kg/d)
      during the first 15 wk PP, and tended to produce more milk over the first 40 wk
      PP (37.1 vs. 35.0 kg/d). Energy balance of cows fed RPC was more negative at wk
      2, 3, and 6 PP, but mean circulating concentrations of fatty acids and beta
      hydroxybutyrate did not differ from those of cows not fed RPC. Despite
      differences in energy balance at 2 and 3 wk PP, mean concentration of hepatic
      triacylglycerol did not differ between RPC treatments. Feeding RPC reduced the
      daily prevalence of subclinical hypocalcemia from 25.5 to 10.5%, as defined by
      concentrations of total Ca of <8.0 mg/dL in serum in the first 7 d PP. Pregnancy
      at first artificial insemination tended to be greater for cows fed RPC (41.3 vs.
      23.6%), but the proportion of pregnant cows did not differ by 40 wk PP. Heifers
      born from singleton calvings from cows fed RPC tended to experience greater daily
      gain between birth and 50 wk of age than heifers from cows not supplemented with
      RPC. Feeding RPC for approximately 38 d during the transition period tended to
      increase yield of milk for 40 wk regardless of amount of energy consumed during
      the pregnant, nonlactating period.

PMID- 29224866
TI  - The effects of L-type amino acid transporter 1 on milk protein synthesis in
      mammary glands of dairy cows.
AB  - The mammary gland requires the uptake of AA for milk protein synthesis during
      lactation. The L-type amino acid transporter 1 (LAT1, encoded by SLC7A5), found
      in many different types of mammalian cells, is indispensable as a transporter of
      essential AA to maintain cell growth and protein synthesis. However, the function
      of LAT1 in regulating milk protein synthesis in the mammary gland of the dairy
      cow remains largely unknown. For the current study, we characterized the
      relationship between LAT1 expression and milk protein synthesis in lactating
      dairy cows and investigated whether the mammalian target of rapamycin complex 1
      (mTORC1) signaling controls the expression of LAT1 in their mammary glands. We
      found that LAT1 and the heavy chain of its chaperone, 4F2, were expressed in
      mammary tissues of lactating cows, with the expression levels of LAT1 and the 4F2
      heavy chain being significantly greater in lactating mammary tissues with high
      milk protein content (milk yield, 33.8 +/- 2.1 kg/d; milk protein concentration
      >3%, wt/vol,; n = 3) than in tissues from cows with low-milk protein content
      (milk yield, 33.7 +/- 0.5 kg/d; milk protein concentration <3%, wt/vol; n = 3).
      Immunofluorescence staining of sectioned mammary tissues from cows with high and
      low milk protein content showed that LAT1 was located on the whole plasma
      membrane of alveolar epithelial cells, suggesting that LAT1 provides essential AA
      to the mammary gland. In cultured mammary epithelial cells from the dairy cows
      with high-milk protein content, knockdown of LAT1 expression decreased cell
      viability and beta-casein expression; in contrast, overexpression of LAT1 had the
      opposite effect. Inhibition of mTORC1 by rapamycin attenuated the phosphorylation
      of molecules related to mTORC1 signaling and caused a marked decrease in LAT1
      expression in the cultured cells; expression of beta-casein also decreased
      significantly. These results suggest that LAT1 is involved in milk protein
      synthesis in the mammary glands of lactating dairy cows and that the mTORC1
      signaling pathway might be a control point for regulation of LAT1 expression,
      which could ultimately be used to alter milk protein synthesis.

PMID- 29224867
TI  - Dairy system, parity, and lactation stage affect enteric methane production,
      yield, and intensity per kilogram of milk and cheese predicted from gas
      chromatography fatty acids.
AB  - Ruminants (and milk production) contribute to global climate change through
      enteric methane emissions (EME), and any attempt to reduce them is complicated by
      the fact that they are difficult and expensive to measure directly. In the case
      of dairy cows, a promising indirect method of estimating EME is to use the milk
      fatty acid profile as a proxy, as a relationship exists between microbial
      activity in the rumen and the molecules available for milk synthesis in the
      mammary gland. In the present study, we analyzed the detailed fatty acid profiles
      (through gas chromatography) of a large number of milk samples from 1,158 Brown
      Swiss cows reared on 85 farms with the aim of testing in the field 2 equations
      for estimating EME taken from a published meta-analysis. The average estimated
      methane yield (CH4 emission per kg of dry matter intake, 21.34 +/- 1.60 g/kg) and
      methane intensity (per kg of corrected milk, 14.17 +/- 1.78 g/kg), and the
      derived methane production (CH4 emissions per day per cow, 357 +/- 109 g/d) were
      similar to those previously published. Using data from model cheese makings from
      individual cows, we also calculated estimated methane intensity per kilogram of
      fresh cheese (99.7 +/- 16.4 g/kg) and cheese solids (207.5 +/- 30.9 g/kg). Dairy
      system affected all EME estimates. Traditional dairy farms, and modern farms
      including corn silage in the TMR exhibited greater estimated methane intensities.
      We found very wide variability in estimated EME traits among different farms
      within dairy system (0.33 to 0.61 of total variance), suggesting the need to
      modify the farms' feeding regimens and management practices to mitigate
      emissions. Among the individual factors, parity order affected all estimated EME
      traits excepted methane yield, with an increase from first lactation to the
      following ones. Lactation stage exhibited more favorable estimated EME traits
      during early lactation, concomitant with the availability of nutrients from body
      tissue mobilization for mammary synthesis of milk. Our results showed a coherence
      between the EME traits estimated from the analysis of milk fatty acids and the
      expectations according to current knowledge. Further research is needed to
      validate the results obtained in this study in other breeds and populations, to
      assess the magnitude of the genetic variation and the potential of these
      phenotypes to be exploited in breeding programs with the aim to mitigate
      emissions.

PMID- 29224868
TI  - Technical note: Validation of the BHBCheck blood beta-hydroxybutyrate meter as a
      diagnostic tool for hyperketonemia in dairy cows.
AB  - Accurate cow-side blood beta-hydroxybutyrate (BHB) detection meters are valuable
      tools for rapid diagnosis of hyperketonemia. The main objective of this study was
      to compare the blood BHB measured in whole blood by the BHBCheck meter
      (PortaCheck, Moorestown, NJ) to a previously validated meter, Precision Xtra
      meter (Abbott Laboratories, Abbott Park, IL) and a colorimetric laboratory assay.
      Samples (n = 426) were collected from postpartum primiparous and multiparous
      Holstein cows (n = 79 cows) enrolled in 1 of 2 experiments (Exp) with different
      sampling schedules (Exp 1: n = 39 cows, 58 samples; Exp 2: n = 40 cows, 368
      samples). In both Exp, whole-blood samples were collected from the coccygeal
      vessels after morning milking, before morning feeding. Blood samples were used
      immediately for BHB quantification via the BHBCheck meter and the Precision Xtra
      meter. Blood was also collected into evacuated tubes containing no additive (Exp
      1) or potassium oxalate/sodium fluoride (Exp 2), which were centrifuged for serum
      or plasma separation and stored at -20 degrees C for subsequent analysis.
      Laboratory quantification of BHB concentration was done by the BHB LiquiColor
      Assay (EKF Diagnostics-Stanbio, Boerne, TX; certified for serum and plasma). Data
      were analyzed by UNIVARIATE, CORR, FREQ, REG, and LOGISTIC procedures of SAS 9.4
      (SAS Institute Inc., Cary, NC). Within this sample set, average parity was 3.3
      lactations and DIM was 14 d. The proportion of samples classified as
      hyperketonemia (BHB >=1.2 mmol/L) was 25, 28, and 31% as determined by the
      colorimetric assay, BHBCheck meter, and Precision Xtra meter, respectively. The
      correlation for BHBCheck meter BHB concentration compared with the colorimetric
      assay concentrations was r = 0.96, with a sensitivity of 91% and specificity of
      93%. Correlation, sensitivity, and specificity of the Precision Xtra meter
      concentrations were 0.97, 98%, and 92%, respectively. Bland-Altman plots
      demonstrated minimal bias for both meters. Area under the receiver operator
      characteristic curve suggests adequate diagnostic accuracy of both meters.
      Overall, accuracy, sensitivity, and specificity of the BHBCheck meter was similar
      to the Precision Xtra meter and laboratory assay, indicating the BHBCheck meter
      is appropriate for use as a cow-side diagnostic test for hyperketonemia in dairy
      cows.

PMID- 29224869
TI  - Effects of straw processing and pen overstocking on the growth performance and
      sorting characteristics of diets offered to replacement Holstein dairy heifers.
AB  - Our objectives were to evaluate the effects of pen-stocking density and straw
      processing on the growth performance, feed-bunk sorting behaviors, and hygiene of
      Holstein dairy heifers. Two corn silage-alfalfa haylage diets diluted with wheat
      straw were offered; diet composition was identical, except that one diet
      contained short (well-processed) straw (SS; 46.0% neutral detergent fiber, 12.9%
      crude protein, 60.7% total digestible nutrients, TDN), and the other long (poorly
      processed) straw (LS; 46.5% neutral detergent fiber, 12.6% crude protein, 60.0%
      TDN; % of dry matter basis). A 2 * 3 factorial arrangement of straw-processing
      (SS or LS) and pen-stocking-density [100, 125, or 150% of capacity] treatments
      was evaluated with 240 Holstein dairy heifers (410 +/- 56.3 kg) that were blocked
      by weight, and then assigned to 24 pens with 4 pens/interactive treatment. For 91
      d, diets were dispersed at 1100 h daily, and bunks were sampled subsequently at
      1300, 1600, 1900, 2200, 0100, and 0600 h during 3 evaluation periods throughout
      the trial. Diets were offered for ad libitum intake, but with minimal orts (<3%);
      as such, particle-size concentration factors were calculated as bunk
      concentration/initial concentration. For the LS diet, particle-size concentration
      factors for large (>19 mm) particles increased linearly from 1.26 to 2.82 across
      sampling times, differing from the SS diet at 2200, 0100, 0600, and 0900 h
      (orts). Similar factors calculated for the SS diet also increased linearly across
      sampling times, but these responses were less severe (1.27 to 1.97). Overall,
      particle-size concentration factors for physically effective fiber exhibited
      responses similar to those observed for large particles, except they were limited
      to narrower ranges for both the SS (1.04 to 1.14) and LS (1.03 to 1.26) diets.
      Despite these differences, daily dry matter intake was not affected by treatment
      (mean = 9.65 kg of dry matter/d), nor was daily intake of TDN (mean = 5.92 kg of
      TDN/d). For SS, heifers housed within overstocked pens exhibited reduced average
      daily gain (ADG) compared with the 100% stocking rate (0.93 vs. 0.99 kg/d). With
      LS processing, ADG differed between the 125 and 150% stocking rates (0.96 vs.
      0.88 kg/d), as did the within-pen coefficient of variation for ADG (10.7 vs.
      18.6%). Hygiene scores (1 = clean, 4 = caked-on manure) for legs (range = 2.1 to
      2.3) and flanks (range = 1.6 to 1.9) indicated heifers stayed acceptably clean,
      but the within-pen coefficient of variation for legs (14.4 vs. 9.0%) and flanks
      (34.2 vs. 23.8%) was greater for overstocked pens compared with the 100% stocking
      density, thereby suggesting hygiene scores were more variable without a free
      stall for each heifer.

PMID- 29224870
TI  - Effect of dose and timing of prostaglandin F2alpha treatments during a Resynch
      protocol on luteal regression and fertility to timed artificial insemination in
      lactating Holstein cows.
AB  - Our objective was to evaluate the effect of a second PGF2alpha treatment (25 mg
      of dinoprost) or a double dose of PGF2alpha (50 mg of dinoprost) during a Resynch
      protocol on luteal regression and pregnancies per artificial insemination (P/AI)
      in lactating dairy cows. Lactating Holstein cows (n = 1,100) were randomly
      assigned at a nonpregnancy diagnosis to receive (1) Ovsynch (control: 100 ug of
      GnRH; 7 d, 25 mg of PGF2alpha; 56 h, 100 ug of GnRH), (2) Ovsynch with a second
      PGF2alpha treatment (GPPG: 100 ug of GnRH; 7 d, 25 mg of PGF2alpha; 24 h, 25 mg
      of PGF2alpha; 32 h, 100 ug of GnRH), or (3) Ovsynch with a double dose of
      PGF2alpha (GDDP: 100 ug of GnRH; 7 d, 50 mg of PGF2alpha; 56 h, 100 ug of GnRH).
      All cows received timed artificial insemination (TAI) approximately 16 h after
      the second GnRH treatment (G2). Pregnancy diagnosis was performed by transrectal
      palpation 39 +/- 3 d after TAI, and pregnancy status was reconfirmed 66 d after
      TAI. Blood samples collected from a subset of cows in each treatment at the first
      PGF2alpha treatment (n = 394) and at G2 (n = 367) were assayed for progesterone
      (P4). Data were analyzed by logistic regression using the GLIMMIX procedure of
      SAS (SAS Institute Inc., Cary, NC). At 39 d after TAI, GPPG cows tended to have
      more P/AI than control cows [35% (137/387) vs. 31% (107/349)], whereas P/AI for
      GDDP cows [32% (118/364)] did not differ from that for control cows. Pregnancy
      loss from 38 to 66 d did not differ among treatments and was 8% (30/362). The
      percentage of cows with complete luteal regression (P4 <0.4 ng/mL at G2) tended
      to differ among treatments and was greater for GPPG cows than for GDDP and
      control cows (94% vs. 88% vs. 88%, respectively). Overall, cows with P4 <1 ng/mL
      at the first PGF2alpha treatment had fewer P/AI than cows with P4 >=1 ng/mL (27%
      vs. 38%), whereas cows with P4 >=0.4 ng/mL at G2 had fewer P/AI than cows with P4
      <0.4 ng/mL (15% vs. 38%). We conclude that adding a second PGF2alpha treatment 24
      h after the first within a Resynch protocol tended to increase the proportion of
      cows undergoing complete luteal regression and P/AI, whereas treatment with a
      double dose of PGF2alpha at a single time did not.

PMID- 29224871
TI  - Short communication: Stall occupancy behavior of Nili Ravi buffaloes (Bubalus
      bubalis) when first introduced to freestall housing.
AB  - The aim of the present study was to assess stall occupancy of Nili Ravi buffaloes
      when first introduced to freestall housing. Thirty Nili Ravi buffaloes of
      different parity, weight, and pregnancy status were enrolled from the dairy farm
      of the University of Veterinary and Animal Sciences, Lahore, Pakistan. All of the
      enrolled animals had no previous experience with freestalls. The selected
      buffaloes were introduced to the freestall shed. During an adaptation period of 7
      d, all buffaloes had 24 h of free access to lie down in 1 of 3 areas: (1)
      freestalls, (2) alleys, and (3) an outside open area. After the adaptation
      period, all buffaloes were housed indoors during nighttime (restricted period) to
      ensure that only freestalls or alleys were available as lying areas. An observer
      monitored animals at 0100 h and recorded the number of animals lying in
      freestalls, in alleys, and in the outside open area. The results indicated that
      during the adaptation period, herd-level freestall occupancy in buffaloes
      remained below 10%. During the restricted period, herd-level stall occupancy was
      0, 13, 50, and 90% on d 1, 2, 5, and 17, respectively. Buffaloes with parity >=3
      took fewer days (6.6 +/- 1.0; mean +/- standard error of the mean) to occupy
      stalls than buffaloes with parity 2, 1, and heifers (13.2 +/- 1.5, 16.7 +/- 2.1,
      and 13.5 +/- 2.1 d, respectively). Body weight and pregnancy status of buffaloes
      did not have any effect on stall occupancy. Buffaloes showed adjacent stall
      occupancy, filling opposite stalls first. The results indicated that older
      buffaloes occupied freestalls earlier than younger buffaloes. Our findings would
      help better manage buffaloes in freestall housing.

PMID- 29224872
TI  - Greenhouse gas emissions from liquid dairy manure: Prediction and mitigation.
AB  - The handling and use of manure on livestock farms contributes to emissions of the
      greenhouse gases (GHG) CH4 and N2O, especially with liquid manure management.
      Dairy farms are diverse with respect to manure management, with practices ranging
      from daily spreading to long-term storage for more efficient recycling of manure
      nutrients for crop production. Opportunities for GHG mitigation will depend on
      the baseline situation with respect to handling and storage, and therefore
      prediction and mitigation at the farm level requires a dynamic description of
      housing systems and storage conditions, and use of treatment technologies. Also,
      effects of treatment and handling on the properties of field-applied manure must
      be taken into account. Storage conditions and manure composition importantly
      define carbon and nitrogen transformations, and the resulting emissions of CH4
      and N2O, as well as CO2 and NH3, which are all important for the GHG balance.
      Currently, inventories for CH4 and N2O emissions from manure are based on
      emission factors for a limited number of production systems, together with
      average annual temperature, but the inherent uncertainty of this approach is a
      barrier toward prediction and mitigation. Although more representative emission
      factors may be determined at country level, this is both challenging and costly,
      and effects of management changes for GHG mitigation are not easily quantified.
      An empirical model of CH4 emissions during storage is discussed that is based on
      daily time steps, and a parameterization based on measurements. A distinction
      between emissions from manure in barns and outside storage facilities is
      important for assessing effects of treatment technologies, such as anaerobic
      digestion, where only posttreatment emissions are affected. Upon field
      application, manure and soil together define the equilibrium distribution of
      labile carbon and nitrogen between bulk soil and manure hotspots. This introduces
      heterogeneity with respect to potential for N2O emissions, which is not
      represented in existing prediction models. Manure treatment and management
      options for GHG mitigation are discussed with emphasis on effects on manure
      volatile solids and N availability. Anaerobic digestion and acidification
      represent treatment technologies that are relevant for GHG mitigation on dairy
      farms.

PMID- 29224873
TI  - A clinical and histopathological comparison of the effectiveness of salicylic
      acid to a compound of inorganic acids for the treatment of digital dermatitis in
      cattle.
AB  - Bovine digital dermatitis (DD) is a painful infectious disease, causing lameness,
      reduced animal welfare, and production losses in dairy herds. The main factors
      contributing to DD are an infection with Treponema spp. and poor hygiene. Topical
      treatment has primarily consisted of antibiotics; however, the demand for
      effective nonantibiotic alternatives is increasing. The objective was to evaluate
      the performance of 3 nonantibiotic topical treatments (salicylic acid and a
      compound of inorganic acids in a 20% solution and in a dry form) on DD in a
      commercial dairy herd. Within the 30-d test period, 42 DD lesions on 33 Holstein
      cows were assigned to receive 1 of the 3 treatments. Lesions were biopsied before
      and after treatment and were clinically evaluated 5 times. Improved lesions were
      clinically defined as either healed (regeneration of the skin) or healing (dry
      lesions covered by a scab). Unhealed lesions were defined as either active [with
      a raw, moist, strawberry-like (granulating) surface] or mature (with a raised
      papillomatous appearance). The effectiveness of treatment was evaluated
      histopathologically using the following scores: 0 (no spirochetes present), 1
      (small number of spirochetes present in the epidermis), 2 (moderate number of
      spirochetes present and reaching an intermediary level in the epidermis), and 3
      (large number of spirochetes present and reaching the deepest part of the
      epidermis or the superficial dermis). The improvement rate was 10/14 (71%) for
      salicylic acid, 11/15 (73%) for the inorganic acid solution, and 8/13 (62%) for
      the inorganic acid powder. The analysis showed no difference among treatments.
      The association between clinical score and histopathological score was determined
      by an odds ratio. The odds ratio of a healed lesion having spirochetes in the
      epidermis was 0.58 and that of an active DD lesion having spirochetes in the
      epidermis was 26.5.

PMID- 29224874
TI  - Prepartum application of internal teat sealant or intramammary amoxicillin on
      dairy heifers: Effect on udder health, survival, and performance.
AB  - Intramammary infusion of antimicrobials (IA) and application of an internal teat
      sealant (ITS) at the end of the lactation is a common strategy to prevent and
      treat intramammary infections during the dry period. In heifers, precalving IA
      has been reported to improve udder health and milk quality; however, the effect
      of ITS in heifers housed in freestall barns is still unknown. The objective of
      this study was to investigate the effect of prepartum application of ITS or IA on
      udder health of dairy heifers. A total of 886 heifers were randomly allocated
      into 1 of 4 treatment groups when they were 245 +/- 3 d pregnant. Control heifers
      (CON) did not receive any treatment. Heifers in the ITS group received the
      application of ITS containing 2.6 g of bismuth subnitrate. Animals in the IA
      group received intramammary administration of 62.5 mg of amoxicillin. Heifers in
      IA+ITS group received intramammary administration of amoxicillin followed by ITS
      application. The follow-up period was 270 d in milk (DIM). Clinical mastitis was
      diagnosed and treated by trained farm personnel throughout the study period.
      Composite milk somatic cell counts (SCC) were determined monthly for the first 9
      mo of lactation by Dairy Herd Improvement Association. Subclinical mastitis was
      defined as a cow having a SCC >200,000 cells/mL for at least 1 test day and not
      diagnosed with clinical mastitis during the study period. At 7 +/- 3 DIM,
      composite milk samples were collected for bacteriological analysis for a subset
      of the study animals. The presence of pathogens in milk at 7 +/- 3 DIM was more
      frequently detected in the CON heifers compared with animals enrolled in the
      treatment groups. Heifers in IA+ITS group had a decreased incidence of clinical
      mastitis compared with CON heifers (12.9 vs. 21.4%). Additionally, the incidence
      of subclinical mastitis was decreased for IA+ITS heifers compared with CON
      counterparts (20.1 vs. 43.8%). During the first 9 mo of lactation, IA and IA+ITS
      heifers had lower SCC linear scores compared with ITS and CON counterparts.
      Although IA+ITS treatment successfully improved udder health, it did not result
      in better milk yield, fertility, and survivability. In conclusion, ITS alone was
      not effective in improving udder health; however, the combination of ITS and IA
      decreased the incidence of clinical and subclinical mastitis during the first 9
      mo of lactation. Additionally, IA+ITS had a long-term effect on the SCC linear
      score throughout the study period.

PMID- 29224875
TI  - Dairy cow preference for different types of outdoor access.
AB  - Dairy cows display a partial preference for being outside, but little is known
      about what aspects of the outdoor environment are important to cows. The primary
      aim of this study was to test the preference of lactating dairy cattle for
      pasture versus an outdoor sand pack during the night. A secondary aim was to
      determine whether feeding and perching behavior changed when cows were provided
      outdoor access. A third objective was to investigate how the lying behavior of
      cows changed when given access to different outdoor areas. Ninety-six lactating
      pregnant cows were assigned to 8 groups of 12 animals each. After a baseline
      phase of 2 d in which cows were kept inside the freestall barn, cows were
      habituated to the outdoor areas by providing them access to each of the 2 options
      for 24 h. Cows were then given access, in random order by group, to either the
      pasture (pasture phase) or the sand pack (sand phase). As we tested the 2 outdoor
      options using space allowances consistent with what would be practical on
      commercial dairy farms, the space provided on pasture was larger (21,000 m2) than
      that provided on the sand pack (144 m2). Cows were tested at night (for 2 nights
      in each condition), from 2000 h until morning milking at approximately 0800 h, as
      preference to be outdoors is strongest at this time. During the next 3 nights
      cows were given access to both outside options simultaneously (choice phase).
      Feeding and perching behaviors were recorded when cows were indoors during the
      day and night periods. Lying behavior was automatically recorded by HOBO data
      loggers (Onset, Bourne, MA). Cows spent more time outside in the pasture phase
      (90.0 +/- 5.9%) compared with the sand phase (44.4 +/- 6.3%). When provided
      simultaneous access to both options, cows spent more time on pasture than on the
      sand pack (90.5 +/- 2.6% vs. 0.8 +/- 0.5%, respectively). Time spent feeding
      indoors during the day did not change regardless of what type of outdoor access
      was provided, but there was a decline in perching during the day when cows were
      provided access to either outdoor option at night. Lying time in the pasture
      phase was lower than in the baseline or sand phase. During the nighttime, lying
      time outside was not different between the sand (55.4 +/- 7.9%) and pasture (52.0
      +/- 7.4%) phases. In summary, cows spent a considerable amount of time outside
      during the night when given the opportunity and showed a preference for a large
      pasture versus a small sand pack as an outdoor area.

PMID- 29224876
TI  - Effect of different forage types on the volatile and sensory properties of bovine
      milk.
AB  - The effect of 3 diets (grass, grass/clover, and total mixed ration) on the
      volatile and sensory properties of bovine milk was assessed over an entire
      lactation season. Little evidence was found of direct transfer of terpenes into
      raw milk from the different diets, and it is likely that the monocultures of
      ryegrass used with and without white clover were factors as these contained very
      few terpenes. Evidence of direct transfer of nonterpene volatiles from forage to
      the subsequent raw milks was probable; however, differences in the protein
      carbohydrate availability and digestion in the rumen appeared to have a greater
      contribution to volatile profiles. Pasteurization significantly altered the
      volatile profiles of all milks. A direct link between the milk fatty acid
      content, forage, and volatile products of lipid oxidation was also evident and
      differences in fatty acid content of milk due to forage may also have influenced
      the viscosity perception of milk. Irish sensory assessors preferred pasteurized
      milk produced from grass-fed cows, with least preference from milk produced from
      total mixed ration diets. beta-Carotene content was significantly higher in milks
      derived from grass or grass/clover and appears to have directly influenced color
      perception. Toluene and p-cresol are both degradation products of beta-carotene
      and along with beta-carotene were identified as potential biomarkers for milk
      derived from pasture. The only correlation that appeared to influence the flavor
      of milk as determined using ranked descriptive analysis was p-cresol. P-Cresol
      appears to be responsible for the barnyard aroma of milk and is also likely
      derived from the deamination and decarboxylation of tryptophan and tyrosine due
      to the higher levels of available protein in the grass and grass/clover diets.
      The highest levels of p-cresol were in the grass/clover diets and are likely due
      to the degradation of the isoflavone formononetin in the rumen, which is present
      in white clover swards.

PMID- 29224877
TI  - Effects of early postpartum sodium salicylate treatment on long-term milk,
      intake, and blood parameters of dairy cows.
AB  - Previous research has shown that cows who receive treatment with nonsteroidal
      anti-inflammatory drugs after calving may have increased milk yield beginning
      near peak lactation, resulting in greater 305-d milk production. It has not been
      demonstrated whether this response is associated with greater feed intake
      following the first 3 wk of lactation. Dry matter intake (DMI) and milk yield
      were measured daily for 56 cows over the first 120 d in milk. Cows in their
      second parity and greater were blocked by parity and alternately enrolled 12 to
      36 h after calving into 1 of 2 treatments: either 3 daily drenches of water or 3
      daily drenches of a similar volume of water containing 125 g of sodium salicylate
      (SAL) beginning 12 to 36 h after calving. Cows were housed in individual stalls
      to monitor DMI. Blood samples were collected before calving and on the last day
      of treatment, as well as at 7, 11, 14, 18, 21, 35, 49, 63, 77, 91, 105, and 120 d
      in milk. The SAL treatment did not affect estimated 305-d milk, fat, or protein
      yields (from monthly test days), daily milk yield or components, energy-corrected
      milk, fat-corrected milk, or DMI; however, an interaction between parity and
      treatment was observed for DMI, where second-parity SAL cows had decreased intake
      with no differences observed in older cows. This resulted in a parity by
      treatment interaction for the ratio of energy-corrected milk to DMI. Similarly,
      no main effects of treatment were observed for plasma glucose, beta
      hydroxybutyrate (BHB), or fatty acid concentrations, but we noted interactions
      between treatment and parity for glucose, BHB, and insulin. Older cows had
      greater plasma glucose and insulin concentrations and decreased plasma BHB
      following SAL but no differences were observed in second parity animals.
      Alterations in glucose and insulin resulted in a tendency for a treatment by time
      interaction for the revised quantitative insulin sensitivity check index. Feeding
      behavior was also altered following SAL administration, resulting in fewer but
      longer meals, as well as a tendency for greater meal weight. A tendency for a
      treatment by week interaction for inter-meal interval was observed, as well as a
      parity by treatment interaction for meal weight. Despite the lack of a milk yield
      response, SAL had a prolonged programming effect on feeding behavior and blood
      variables over the first 120 DIM, with responses largely dependent on parity.

PMID- 29224878
TI  - Short communication: Variability in milk urea nitrogen and dairy total mixed
      ration composition in the northeastern United States.
AB  - The main objective of this survey was to examine variability in milk urea
      nitrogen (MUN) for Dairy Herd Improvement Association (DHIA) herds in the
      northeastern United States (the Northeast), examine trends in dairy cow diet
      composition, and determine potential relationships for MUN and diet composition.
      Trends in milk fat and protein concentrations, milk yield, days in milk on test
      day, and lactation number of the cows were also evaluated. The data set for the
      survey included 10,839,461 DHIA dairy cow records from 2004 to 2015 for 13 states
      (CT, DE, MA, MD, ME, NH, NJ, NY, PA, RI, VA, VT, and WV) and was retrieved from
      Dairy Records Management Systems (Raleigh, NC). Average (across states and years)
      milk yield, milk fat, and milk protein were 31.6 +/- 0.24 kg/d, 3.85 +/- 0.021%,
      and 3.13 +/- 0.013%, respectively. No obvious trends were observed for milk fat
      or protein content, but milk yield steadily increased during the survey period.
      Milk urea N concentration averaged 13.3 +/- 0.13 mg/dL, with no obvious or
      consistent trends. Examination of variability in dairy feed cost and all milk
      price for the Northeast indicated that high MUN generally coincided with high
      feed cost and high milk price. For the diet composition survey, 9,707 records of
      total mixed ration (TMR) analyses, unrelated to the milk composition data set,
      from the Cumberland Valley Analytical Service (Maugansville, MD) database were
      examined. Concentration of TMR crude protein (CP) decreased from 17.1% in 2007 to
      16.4% in 2015, but there was not an obvious trend in soluble protein
      concentration. Concentration of TMR neutral detergent fiber (NDF) and 24-h in
      vitro NDF degradability declined steadily during the survey period and was
      accompanied by a steady increase in TMR starch concentration. Examination of
      these unrelated data sets revealed lack of correlation between MUN and diet
      chemical composition. Thus, we conclude that individual cow MUN in Northeast
      dairy herds fluctuated between 2004 and 2015. It appeared that MUN followed
      variability in feed cost; however, ration feed ingredient data were not available
      to better define the reasons for the variations in MUN.

PMID- 29224879
TI  - Plant oil supplements reduce methane emissions and improve milk fatty acid
      composition in dairy cows fed grass silage-based diets without affecting milk
      yield.
AB  - Four lipid supplements varying in chain length or degree of unsaturation were
      examined for their effects on milk yield and composition, ruminal CH4 emissions,
      rumen fermentation, nutrient utilization, and microbial ecology in lactating
      dairy cows. Five Nordic Red cows fitted with rumen cannulas were used in a 5 * 5
      Latin square with five 28-d periods. Treatments comprised total mixed rations
      based on grass silage with a forage-to-concentrate ratio of 60:40 supplemented
      with no lipid (CO) or 50 g/kg of diet dry matter (DM) of myristic acid (MA),
      rapeseed oil (RO), safflower oil (SO), or linseed oil (LO). Feeding MA resulted
      in the lowest DM intake, and feeding RO reduced DM intake compared with CO.
      Feeding MA reduced the yields of milk, milk constituents, and energy-corrected
      milk. Plant oils did not influence yields of milk and milk constituents, but
      reduced milk protein content compared with CO. Treatments had no effect on rumen
      fermentation characteristics, other than an increase in ammonia-N concentration
      due to feeding MA, RO, and SO compared with CO. Lipid supplements reduced daily
      ruminal CH4 emission; however, the response was to some extent a result of lower
      feed intake. Lipids modified microbial community structure without affecting
      total counts of bacteria, archaea, and ciliate protozoa. Dietary treatments had
      no effect on the apparent total tract digestibility of organic matter, fiber, and
      gross energy. Treatments did not affect either energy secreted in milk as a
      proportion of energy intake or efficiency of dietary N utilization. All lipids
      lowered de novo fatty acid synthesis in the mammary gland. Plant oils increased
      proportions of milk fat 18:0, cis 18:1, trans and monounsaturated fatty acids,
      and decreased saturated fatty acids compared with CO and MA. Both SO and LO
      increased the proportion of total polyunsaturated fatty acids, total conjugated
      linolenic acid, and cis-9,trans-11 conjugated linoleic acid. Feeding MA clearly
      increased the Delta9 desaturation of fatty acids. Our results provide compelling
      evidence that plant oils supplemented to a grass silage-based diet reduce ruminal
      CH4 emission and milk saturated fatty acids, and increase the proportion of
      unsaturated fatty acids and total conjugated linoleic acid while not interfering
      with digestibility, rumen fermentation, rumen microbial quantities, or milk
      production.

PMID- 29224880
TI  - The effect of different treatments for early-lactation hyperketonemia on liver
      triglycerides, glycogen, and expression of key metabolic enzymes in dairy cattle.
AB  - Despite the widespread use of treatments for postpartum hyperketonemia in dairy
      cows, there is currently a lack of evidence comparing their effects on both the
      resolution of hyperketonemia and the potential effects on the liver of affected
      animals. The objective of our work was to investigate the effect of commonly used
      hyperketonemia treatments on hepatic triglyceride and glycogen content as well as
      on the mRNA and protein abundance of key enzymes involved in gluconeogenesis,
      ketogenesis, and lipid metabolism. Multiparous Holstein cows between 3 and 9 d in
      milk were screened 3 times per week and enrolled in the study when whole-blood
      beta-hydroxybutyrate concentrations measured >=1.2 mmol/L. Cows were randomly
      allocated to 1 of 4 groups: (1) 500 mL of a 50% d-glucose solution intravenously
      once a day for 3 d (n = 8), (2) 300 mL of propylene glycol orally once a day for
      3 d (n = 8), (3) 500 mL of a 50% d-glucose solution intravenously and 300 mL of
      propylene glycol orally once a day for 3 d (n = 8), or (4) an untreated control
      group (n = 8). Liver biopsies were taken on the day of enrollment as well as on
      the day following completion of treatments. Liver triglyceride and glycogen
      content were determined by colorimetric and fluorometric methods, respectively.
      Gene and protein expression of pyruvate carboxylase, phosphoenolpyruvate
      carboxykinase 1, glucose-6-phosphatase, 3-hydroxy-3-methylglutaryl-CoA synthase
      2, acetyl-CoA carboxylase, and carnitine palmitoyltransferase 1A were compared
      between groups and time points using quantitative reverse transcriptase PCR and
      Western blotting techniques, respectively. In addition, the ratio of light chain
      3B II:I was determined by Western blotting. Plasma samples from both time points
      for each enrolled cow were submitted for chemistry analysis. Data were analyzed
      using a repeated-measures ANOVA taking into account the paired nature of the
      data, and differences between all groups and time points were controlled for
      multiple comparisons using the Tukey procedure. No difference was found in
      triglyceride or glycogen concentration between treatment groups. The gene
      expression of pyruvate carboxylase decreased in the group receiving both
      treatments, whereas protein expression of this enzyme increased in all groups
      over time. The autophagy marker light chain 3B II:I decreased in the group
      receiving both glucose and propylene glycol. No other changes in gene or protein
      expression of key hepatic enzymes were associated with treatments. We conclude
      that intravenous glucose and oral propylene glycol, commonly used treatments for
      ketosis in postpartum dairy cows, administered alone or in combination for a
      duration of 3 d did not have important beneficial or detrimental effects on
      selected indicators of liver composition and function in cows with
      hyperketonemia.

PMID- 29224881
TI  - Early-lactation extended pirlimycin therapy against naturally acquired
      Staphylococcus aureus intramammary infections in heifers: A randomized controlled
      trial.
AB  - The primary objective of the current study was to evaluate cure rate following an
      early-lactation extended intramammary pirlimycin treatment on heifers naturally
      infected by Staphylococcus aureus. The secondary objective was to assess
      Petrifilm Staph Express (3M Microbiology, St. Paul, MN) count plate
      characteristics when used in a protocol for early-lactation detection of infected
      quarters in heifers. Milk samples were collected from heifers (n = 946) in the
      first few days following calving (mean = 5 d). Heifers with laboratory-confirmed
      S. aureus intramammary infection (n = 72) were randomly allocated into 2 groups.
      The treatment group (n = 54 quarters from 38 heifers) received an intramammary
      infusion of 50 mg of pirlimycin once per day for 8 consecutive days in infected
      quarters. The control group (n = 44 quarters from 34 heifers) did not receive any
      treatment. Treatment success was defined as having negative culture results for
      S. aureus in all 3 post-treatment quarter milk samples collected on d 17, 24, and
      31 post-treatment. Treatment group mammary quarters showed a statistically
      significant higher cure rate (64.8%) compared with the control group (34.1%). A
      total of 38% of quarters identified as S. aureus-positive using the Petrifilm
      Staph Express count plate were in fact identified as non-aureus staphylococci on
      routine laboratory-based bacteriological culture. The current study demonstrates
      that a higher cure rate for S. aureus IMI can be achieved in dairy heifers if an
      extended treatment protocol is put in place soon after calving. Use of Petrifilm
      Staph Express count plate for identification of S. aureus-infected heifers could
      lead to unnecessary treatments because of false-positive results.

PMID- 29224882
TI  - Genetic parameters for alphaS1-casein and alphaS2-casein phosphorylation isoforms
      in Dutch Holstein Friesian.
AB  - Relative concentrations of alphaS1-casein and alphaS2-casein (alphaS1-CN and
      alphaS2-CN) phosphorylation isoforms vary considerably among milk of individual
      cows. We estimated heritabilities for alphaS2-CN phosphorylation isoforms,
      determined by capillary zone electrophoresis from 1,857 morning milk samples, and
      genetic correlations among alphaS2-CN phosphorylation isoforms in Dutch Holstein
      Friesian. To investigate if phosphorylation of alphaS1-CN and alphaS2-CN are due
      to the same genetic mechanism, we also estimated genetic correlations between
      alphaS1-CN and alphaS2-CN phosphorylation isoforms as well as the genetic
      correlations between the phosphorylation degrees (PD) of alphaS1-CN and alphaS2
      CN defined as the proportion of isoforms with higher degrees of phosphorylation
      in total alphaS1-CN and alphaS2-CN, respectively. The intra-herd heritabilities
      for the relative concentrations of alphaS2-CN phosphorylation isoforms were high
      and ranged from 0.54 for alphaS2-CN-10P to 0.89 for alphaS2-CN-12P. Furthermore,
      the high intra-herd heritabilities of alphaS1-CN PD and alphaS2-CN PD imply a
      strong genetic control of the phosphorylation process, which is independent of
      casein production. The genetic correlations between alphaS2-CN phosphorylation
      isoforms are positive and moderate to high (0.33-0.90). Furthermore, the strong
      positive genetic correlation (0.94) between alphaS1-CN PD and alphaS2-CN PD
      suggests that the phosphorylation processes of alphaS1-CN and alphaS2-CN are
      related. This study shows the possibility of breeding for specific alphaS1-CN and
      alphaS2-CN phosphorylation isoforms, and relations between the phosphorylation
      degrees of alphaS1-CN and alphaS2-CN and technological properties of milk need to
      be further investigated to identify potential benefits for the dairy industry.

PMID- 29224884
TI  - A genome-wide association study for left-sided displacement of the abomasum using
      a high-density single nucleotide polymorphism array.
AB  - Left-sided displacement of the abomasum (LDA) is a frequent disease in dairy
      cattle causing significant financial losses for dairy farmers. Heritability (h2)
      of this complex disease was estimated at up to 0.5 in German Holstein (GH)
      cattle. Using the Bovine High Density BeadChip (Illumina Inc., San Diego, CA)
      comprising 588,753 single nucleotide polymorphisms (SNP) after quality control
      for 126 LDA cases and 280 population-based controls, we used a mixed linear model
      analysis in a genome-wide association study (GWAS). We identified 6 genomic
      regions for LDA on bovine chromosomes 2, 8, 13, 20, 24, and X that were
      significantly associated with LDA. Each of these regions was covered by 4 to 12
      LDA-associated SNP. Single SNP within these regions explained up to 7.3% of the
      phenotypic variance. An independent sample of 1,554 GH cows, including 539
      controls and 1,015 cases, were genotyped for 8 SNP highly associated with LDA on
      Bos taurus autosomes (BTA) 2, 8, 13, and 24, as well as 6 SNP located in
      previously identified LDA regions on BTA1, 5, 11, and 27 using competitive allele
      specific PCR genotyping technology (KASP). The analysis using the KASP genotypes
      confirmed LDA-associated loci on BTA2, 8, 13, and 27. These genomic regions may
      contribute to the susceptibility to LDA in Holstein cows and may harbor
      functional variants for LDA.

PMID- 29224883
TI  - Utilization of protein in red clover and alfalfa silages by lactating dairy cows
      and growing lambs.
AB  - Feeding trials were conducted with lactating cows and growing lambs to quantify
      effects of replacing dietary alfalfa silage (AS) with red clover silage (RCS) on
      nutrient utilization. The lactation trial had a 2 * 4 arrangement of treatments:
      AS or RCS fed with no supplement, rumen-protected Met (RPM), rumen-protected Lys
      (RPL), or RPM plus RPL. Grass silage was fed at 13% of dry matter (DM) with AS to
      equalize dietary neutral detergent fiber (NDF) and crude protein contents. All
      diets contained (DM basis) 5% corn silage and 16% crude protein. Thirty-two
      multiparous (4 ruminally cannulated) plus 16 primiparous Holstein cows were
      blocked by parity and days in milk and fed diets as total mixed rations in an
      incomplete 8 * 8 Latin square trial with four 28-d periods. Production data (over
      the last 14 d of each period) and digestibility and excretion data (at the end of
      each period) were analyzed using the MIXED procedure of SAS (SAS Institute Inc.,
      Cary, NC). Although DM intake was 1.2 kg/d greater on AS than RCS, milk yield and
      body weight gain were not different. However, yields of fat and energy-corrected
      milk as well as milk content of fat, true protein, and solids-not-fat were
      greater on AS. Relative to AS, feeding RCS increased milk and energy-corrected
      milk yield per unit of DM intake, milk lactose content, and apparent N efficiency
      and reduced milk urea. Relative to AS, apparent digestibility of DM, organic
      matter, NDF, and acid detergent fiber were greater on RCS, whereas apparent and
      estimated true N digestibility were lower. Urinary N excretion and ruminal
      concentrations of ammonia, total AA, and branched-chain volatile fatty acids were
      reduced on RCS, indicating reduced ruminal protein degradation. Supplementation
      of RPM increased intake, milk true protein, and solids-not-fat content and tended
      to increase milk fat content. There were no silage * RPM interactions, suggesting
      that RPM was equally limiting on both AS and RCS. Supplementation of RPL did not
      influence any production trait; however, a significant silage * RPL interaction
      was detected for intake: RPL reduced intake of AS diets but increased intake of
      RCS diets. Duplicated metabolism trials were conducted with lambs confined to
      metabolism crates and fed only silage. After adaptation, collections of silage
      refusals and excreta were made during ad libitum feeding followed by feeding DM
      restricted to 2% of body weight. Intake of DM was not different when silages were
      fed ad libitum. Apparent digestibility of DM, organic matter, NDF, and
      hemicellulose was greater in lambs fed RCS on both ad libitum and restricted
      intake; however, acid detergent fiber digestibility was only greater at
      restricted intake. Apparent and estimated true N digestibility was substantially
      lower, and N retention was reduced, on RCS. Results confirmed greater DM and
      fiber digestibility in ruminants and N efficiency in cows fed RCS. Specific loss
      of Lys bioavailability on RCS was not observed. Based on milk composition, Met
      was the first-limiting AA on both silages; however, Met was not limiting based on
      production and nutrient efficiency. Depressed true N digestibility suggested
      impaired intestinal digestibility of rumen-undegraded protein from RCS.

PMID- 29224885
TI  - Economic optimization of selective dry cow treatment.
AB  - The objective of this study was to develop a mathematical model to identify a
      scenario with the lowest costs for mastitis associated with the dry period while
      restricting the percentage of cows to be dried off with dry cow antimicrobials.
      Costs of clinical and subclinical mastitis as well as antimicrobial use were
      quantified. Based on data from a large field trial, a linear programming model
      was built with the goal to minimize the costs associated with antimicrobial use
      at drying off. To enable calculations on minimizing costs of dry cow treatment on
      herd-level by drying-off decisions in an "average" herd, we created an example
      herd. Cows were projected on 3 different types of herds, based on bulk tank
      somatic cell count, and were categorized in groups based on parity and somatic
      cell count from the last test recording before drying-off. Economically optimal
      use of antimicrobials was determined while restricting the maximum percentage of
      cows dried off with antimicrobials from 100 to 0%. This restriction reveals the
      relationship between the maximum percentage of cows dried off with antibiotics
      and the economic consequences. A sensitivity analysis was performed to evaluate
      the effect of variation in the most important input variables, with the effect of
      dry cow antimicrobials resulting in a lower or higher percentage of clinical and
      subclinical mastitis depending on being dried off with or without dry cow
      antimicrobials, respectively, and the milk price. From an economic perspective,
      blanket dry cow treatment seems not to be the optimal approach of dry cow
      therapy, although differences between approaches were small. With lower bulk tank
      somatic cell counts, more dry cow antimicrobials can be omitted without economic
      consequences. The economic impact of reducing the percentage of clinical mastitis
      was found to be much larger than reducing the bulk tank somatic cell count. The
      optimal percentage of cows to be dried off with antimicrobials depends on the
      udder health situation, expressed as the bulk tank somatic cell count and the
      incidence of clinical mastitis. For all evaluated types of herds, selective dry
      cow treatment was economically more beneficial than blanket dry cow treatment.
      Economic profits of selective dry cow treatment are greater if bulk tank somatic
      cell count and clinical mastitis incidence are lower. Economics is not an
      argument against reduction of dry cow antimicrobials by applying selective dry
      cow treatment.

PMID- 29224886
TI  - [Spheroids: A reference model for in vitro culture of solid tumors?]
AB  - The recognition that solid tumors are complex entities composed of the tumor cell
      mass itself and a stromal micro-environnement providing a variety of cells from
      the host (fibroblasts, endothelial cells, immune cells) led to recognize that
      this heterogeneity could not be recapitulated in vitro by conventional
      bidimensional (2-D) cultures. This justified numerous attempts to develop
      tridimensional (3-D) cultures that provided better tools for approaching tumor
      complexity and more convincing drug testing systems. Among various 3-D
      technologies, tumor spheroids are more likely suited to provide in vitro
      platforms for apprehending specific aspects of different processes specifically
      defining each tumor category as well as testing drug delivery systems. This
      review summarizes current features of multicellular tumor spheroids and their
      suitability for studying different aspects of cancer cell biology, patient
      specific therapies and drug treatment.

PMID- 29224887
TI  - Ambient air pollution: How much of estimated "prenatal exposure" is truly
      attributable to pre-birth exposures?

PMID- 29224888
TI  - Anthropogenic eutrophication affects the body size of Cymodocea nodosa in the
      North Aegean Sea: A long-term, scale-based approach.
AB  - The variation of eleven Cymodocea nodosa metrics was studied along two
      anthropogenic gradients in the North Aegean Sea, in two separate periods (July
      2004 and July 2013). The aim was to specify existing monitoring programs on
      different kind of human-induced or natural stress for a better decision-making
      support. Key water variables (N-NO2, N-NO3, N-NH4, P-PO4, Chl-a, attenuation
      coefficient-K, and suspended solids) along with the stress index MALUSI were also
      estimated in each sampling effort. All metrics (except one) showed significant
      differences (p<0.05) and highest variation at the meadows scale in both sampling
      periods. The body size, e.g., CymoSkew, total and maximum leaf length, and leaf
      area (cm2/shoot), rather than the abundance, e.g., shoot density (shoots/m2),
      leaf area index (m2/m2), metrics were related to anthropogenic eutrophication
      variables represented by N-NH4, N-NO3, N/P and MALUSI. The temporal analysis was
      restricted to two (2) meadows and water variables that were common between the
      two periods. PERMANOVA and PCA of common meadows and metrics within nine years
      showed significant but not consistent differences. While the most impacted
      studied site of Viamyl remained unchanged, a significant improvement of water
      quality was observed in the second most impacted meadow of Nea Karvali, which
      however was reduced to half of its previous area. On the one hand that was the
      result of combined management practices in nearby aquacultures and lower
      industrial activities due to the economic crisis. On the contrary, dredging and
      excess siltation from changes in land catchments and construction of permanent
      structures may decrease seagrass abundance.

PMID- 29224889
TI  - Perioperative Internal Iliac Artery Balloon Occlusion, In the Setting of Placenta
      Accreta and Its Variants: The Role of the Interventional Radiologist.
AB  - Placenta accreta and its variants (increta and percreta) are conditions of
      abnormal placentation that are encountered with increasing frequency. The
      spectrum of placenta accreta (including placenta increta and percreta) involves
      an abnormal attachment of the placental chorionic villi to the uterine
      myometrium. This abnormal attachment leads to increased adherence of the placenta
      to the uterus and abnormal placental-uterine separation at the time of delivery.
      Placental invasion into, or through the myometrium is associated with increased
      postpartum morbidity and mortality as a result of uterine hemorrhage during and
      following cesarean section. A multidisciplinary clinical approach to the
      treatment of patients with placenta accreta is recommended by the American
      College of Obstetricians and Gynecologists. As potential members of an
      interdisciplinary team, interventional radiologists can perform prophylactic
      internal iliac arterial balloon occlusion as an adjunctive therapy for reducing
      potentially life-threatening postpartum hemorrhage. The procedure involves
      placement of a balloon catheter into the internal iliac or common iliac arteries
      bilaterally prior to cesarean section. Following delivery, and prior to placental
      separation, the catheter balloons are inflated with a pre-determined volume of
      saline leading to transient occlusion of the internal iliac arteries and reduced
      uterine blood flow.

PMID- 29224890
TI  - Advances in breast intervention: where are we now and where should we be?
AB  - In the past four decades, a variety of methods for minimal or non-invasive
      diagnosis and treatment of breast cancer have been introduced. Although breast
      imaging has become more and more specific for diagnosis, specimen biopsy with
      histopathological confirmation is still necessary. Core-needle biopsy under
      ultrasound guidance is the appropriate first choice for the diagnosis of most
      lesions. Fine-needle aspiration is of interest for identification of the presence
      of metastatic disease in abnormal lymph nodes. For microcalcifications, vacuum
      assisted biopsy is recommended, especially with stereotactic guidance. In recent
      years different therapeutic techniques have been developed for the treatment of
      solid lesions, including breast cancer. Certainly, with the improvement of
      technology and medical scientific progress, it is becoming more common to use
      minimal- or non-invasive therapies. The proposed minimally invasive techniques
      may offer complete treatment of breast cancer, with better cosmetic results, less
      psychological stress, and shorter hospital stays. In this article, the strengths
      and weaknesses of the different diagnostic and therapeutic techniques are
      presented, and promising techniques for the future are discussed.

PMID- 29224891
TI  - The Bmp signaling pathway regulates development of left-right asymmetry in
      amphioxus.
AB  - Establishment of asymmetry along the left-right (LR) body axis in vertebrates
      requires interplay between Nodal and Bmp signaling pathways. In the basal
      chordate amphioxus, the left-sided activity of the Nodal signaling has been
      attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal
      organs, however the role of Bmp signaling in LR asymmetry establishment has not
      been addressed to date. Here, we show that Bmp signaling is necessary for the
      development of LR asymmetric morphogenesis of amphioxus larvae through regulation
      of Nodal signaling. Loss of Bmp signaling results in loss of the left-sided
      expression of Nodal, Gdf1/3, Lefty and Pitx and in gain of ectopic expression of
      Cerberus on the left side. As a consequence, the larvae display loss of the
      offset arrangement of axial structures, loss of the left-sided pharyngeal organs
      including the mouth, and ectopic development of the right-sided organs on the
      left side. Bmp inhibition thus phenocopies inhibition of Nodal signaling and
      results in the right isomerism. We conclude that Bmp and Nodal pathways act in
      concert to specify the left side and that Bmp signaling plays a fundamental role
      during LR development in amphioxus.

PMID- 29224892
TI  - How glucose, glutamine and fatty acid metabolism shape blood and lymph vessel
      development.
AB  - Recently, endothelial cell metabolism has emerged as an essential driver and
      regulator of both blood and lymph vessel development. Evidence rapidly builds
      that metabolism is not only necessary for endothelial cell function, but moreover
      controls several aspects of the (lymph)-angiogenic process. So far, the best
      characterized metabolic pathways to have an impact on angiogenesis are
      glycolysis, fatty acid oxidation and glutamine metabolism. Glycolysis regulates
      tip cell behavior by providing ATP, fatty acid oxidation controls stalk cell
      proliferation by producing nucleotide biomass, and glutamine metabolism is
      critical for tip and stalk cell dynamics by supporting Krebs cycle anaplerosis,
      protein production and redox homeostasis, and links to asparagine metabolism.
      During lymphangiogenesis, glycolysis and fatty acid oxidation are key metabolic
      pathways. Glycolysis provides energy for growing lymph vessels, while fatty acid
      oxidation is a critical metabolic regulator of lymphangiogenesis, in part by
      promoting nucleotide synthesis as well as by mediating epigenetic changes of
      histone acetylation, which promotes transcription of key lymphatic genes, and
      hence venous-to-lymphatic endothelial cell differentiation. On the whole,
      increasing knowledge on the metabolic landscape of endothelial cells offers a
      fresh impetus to future treatment possibilities of vascular related diseases.

PMID- 29224893
TI  - External validation of equations to estimate resting energy expenditure in 14952
      adults with overweight and obesity and 1948 adults with normal weight from Italy.
AB  - BACKGROUND & AIMS: We cross-validated 28 equations to estimate resting energy
      expenditure (REE) in a very large sample of adults with overweight or obesity.
      METHODS: 14952 Caucasian men and women with overweight or obesity and 1498 with
      normal weight were studied. REE was measured using indirect calorimetry and
      estimated using two meta-regression equations and 26 other equations. The correct
      classification fraction (CCF) was defined as the fraction of subjects whose
      estimated REE was within 10% of measured REE. RESULTS: The highest CCF was 79%,
      80%, 72%, 64%, and 63% in subjects with normal weight, overweight, class 1
      obesity, class 2 obesity, and class 3 obesity, respectively. The Henry weight and
      height and Mifflin equations performed equally well with CCFs of 77% vs. 77% for
      subjects with normal weight, 80% vs. 80% for those with overweight, 72% vs. 72%
      for those with class 1 obesity, 64% vs. 63% for those with class 2 obesity, and
      61% vs. 60% for those with class 3 obesity. The Sabounchi meta-regression
      equations offered an improvement over the above equations only for class 3
      obesity (63%). CONCLUSIONS: The accuracy of REE equations decreases with
      increasing values of body mass index. The Henry weight & height and Mifflin
      equations are similarly accurate and the Sabounchi equations offer an improvement
      only in subjects with class 3 obesity.

PMID- 29224894
TI  - The biology of language?.

PMID- 29224895
TI  - In sailing the fun is in the travelling!

PMID- 29224896
TI  - Special Section: Biological Waste to Energy.

PMID- 29224897
TI  - Foot exercise and orthotics more effective than knee exercise in PFJ pain.

PMID- 29224898
TI  - Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated
      Phase I Unit.
AB  - AIMS: Advanced biliary tract carcinomas (ABC) are malignancies with limited
      effective therapies for advanced disease. There is little published evidence of
      outcomes of ABC patients participating in phase I clinical trials. MATERIALS AND
      METHODS: Patient characteristics, treatment details and outcomes of ABC patients
      treated at a dedicated phase I unit were captured and analysed from case and
      trial records. RESULTS: In total, 123 ABC patients were included in the study, of
      which 48 patients participated in 41 different phase I trials; 75 (61%) did not
      participate due to rapid disease progression or patient choice. Molecular
      characterisation of tumours using a targeted panel was conducted in 15 (31%),
      yielding several potentially actionable mutations, including BRCA, PIK3CA, FGFR,
      AKT and PTEN loss. Of the 39 evaluable patients there was one exceptional
      responder. Eighteen (46%) other patients achieved stable disease as their best
      response, with a clinical benefit rate at 4 months of 10%. Treatment was
      generally well tolerated with grade 3 or 4 adverse events only observed in eight
      patients (17 %), of which six were drug related and led to trial discontinuation
      in one (3%), with no toxicity-related deaths. CONCLUSION: Carefully selected ABC
      patients have been found to tolerate experimental phase I clinical trials without
      excess toxicity. The aggressive nature of this disease warrants consideration of
      early referral to a phase I unit. Future work will require comprehensive
      molecular profiling in an attempt to understand the biology underlying the
      exceptional responders and to match patients in real-time to targeted therapies.

PMID- 29224899
TI  - Re-irradiation and Hyperthermia in Breast Cancer.
AB  - Half of locoregional recurrences after breast cancer treatment are isolated
      events. Restaging should be carried out to select patients for curative salvage
      treatment. The approach depends on the characteristics of the primary and
      recurrent cancer, previous locoregional and systemic treatments, site of
      recurrence, comorbidities and the patient's wishes. A multidisciplinary
      discussion should be associated with the shared decision-making process. In view
      of the potential long-term disease-free survival, meticulous target volume
      delineation and selection of the most appropriate techniques should be used to
      decrease the risk of toxicity. This overview aims to provide clinicians with
      tools to manage the different scenarios of breast cancer patients with
      locoregional recurrences in the context of re-irradiation.

PMID- 29224900
TI  - Single Fraction Stereotactic Ablative Body Radiotherapy for Oligometastasis:
      Outcomes from 132 Consecutive Patients.
AB  - AIMS: Stereotactic ablative body radiotherapy (SABR) is currently used to treat
      oligometastases, but the optimum dose/fractionation schedule is unknown. In this
      study, we evaluated outcomes after single fraction SABR in patients with
      oligometastatic disease. MATERIALS AND METHODS: Single institutional
      retrospective review of patients treated with single fraction SABR for one to
      three oligometastases between 2010 and 2015. The primary outcome was freedom from
      widespread disease defined as distant recurrence not amenable to surgery or SABR;
      or recurrence with four or more metastases. RESULTS: In total, 186 treatments
      were delivered in 132 patients. The two most common target sites were lung (51%)
      and bone (40%). The most frequent single fraction prescription dose was 26 Gy
      (47%). The most common primary malignancy was genitourinary (n = 46 patients).
      Freedom from widespread disease was 75% at 1 year (95% confidence interval 67
      83%) and 52% at 2 years (95% confidence interval 42-63%). Freedom from local
      progression at 1 year was 90% (95% confidence interval 85-95%) and at 2 years was
      84% (95% confidence interval 77-91%). A compression fracture of the lumbar
      vertebra was the only grade 3+ treatment-related toxicity. CONCLUSIONS: Single
      fraction SABR is associated with a high rate of freedom from widespread disease,
      favourable local control and low toxicity comparable with historic multi-fraction
      SABR reports.

PMID- 29224901
TI  - External Beam Re-irradiation in Rectal Cancer.
AB  - Locally recurrent rectal cancer results in significant symptoms and is associated
      with prognosis of less than 1 year unless radical resection can be offered.
      Unfortunately, radical resection rates are low and therefore strategies to
      palliate symptoms and to maximise downstaging are of significant interest. As the
      majority of those presenting with locally recurrent rectal cancer will have
      received previous irradiation for their primary tumour, re-irradiation may offer
      benefit in this setting. The literature to date is considered in both palliative
      patients and those with potentially operable disease. Palliative patients gain
      significant symptomatic relief from standard dose fractionations of up to 30 Gy.
      In potentially operable patients, the evidence is discussed in the context of key
      questions; including indications for treatment, dose and fractionation,
      radiotherapy technique, margins and constraints. Finally, we highlight some
      additional areas of interest for consideration in future research and
      development.

PMID- 29224902
TI  - Positron emission tomography/computed tomography evaluation of oncolytic virus
      therapy efficacy in melanoma.

PMID- 29224903
TI  - Eighth American Joint Committee on Cancer (AJCC) melanoma classification: Let us
      reconsider stage III.

PMID- 29224904
TI  - Comment on predictors of daily life suicidal ideation in adults recently
      discharged after a serious suicide attempt: A pilot study.

PMID- 29224905
TI  - The mechanics of corneal deformation and rupture for penetrating injury in the
      human eye.
AB  - Penetrating eye injuries are surgical emergencies with guarded visual prognosis.
      The purpose of the current study was to determine the force required to rupture
      the cornea with a penetrating object, and to study how this force is affected by
      the object geometry. Thirty-six human cadaveric eyes from donors of various ages
      were characterized for diameter, axial length, and pre-test intraocular pressure.
      In order to investigate the effects of specimen storage time on the tissue
      response, half of the specimens were tested within two weeks of donor expiration,
      and half of the specimens were stored at -4 degrees C for 12-18 months. Indenters
      of three different diameters (1.0, 1.5, and 2.0mm) were lowered into the apex of
      the cornea until rupture. Resistance to displacement (stiffness), displacement at
      failure, and the force at failure were determined. Multi-variable regression
      analysis was used to determine associations of the input variables (indenter
      size, test speed, and tissue postmortem time) on the mechanics of the tissue
      response. Twenty-nine of the 36 specimens failed at the indenter location in the
      cornea, four failed at the limbus, and three failed in the sclera near sites of
      muscle attachment. The average force at failure caused by the 1.0mm, 1.5mm, and
      2.0mm indenters increased from 30.5+/-5.5N to 40.5+/-8.3N to 58.2+/-14.5N,
      respectively (p<0.002). The force at failure was associated with the donor age
      (p<0.001), and globe diameter (p<0.041), but was not associated with pre-test
      intraocular pressure, tissue postmortem time, axial length, or speed of the
      indenter. This study has quantified the force-displacement and failure response
      of a large series of human cadaveric eyes subjected to penetrating indentation
      loads on the cornea. The results provide useful data for characterizing the
      relationship between corneal rupture and the geometry of a penetrating object.

PMID- 29224906
TI  - Horse-related injuries in children - unmounted injuries are more severe: A
      retrospective review.
AB  - INTRODUCTION: Horse-related injuries account for one quarter of all paediatric
      sports fatalities. It is not known whether the pattern of injury spectrum and
      severity differ between children injured whilst mounted, compared with those
      injured unmounted around horses. We aimed to identify any distinctions between
      the demographic features, spectrum and severity of injuries for mounted versus
      unmounted patients. PATIENTS AND METHODS: Trauma registry data were reviewed for
      505 consecutive paediatric patients (aged<16years) admitted to a large paediatric
      trauma centre with horse-related injuries over a 16-year period. Patients were
      classified into mounted and unmounted groups, and demographics, injury spectrum,
      injury severity, and helmet usage compared using odds ratios and Wilcoxon rank
      sum tests. RESULTS: More patients (56%) were injured in a private setting than in
      a sporting or supervised context (23%). Overall, head injuries were the most
      common horse-related injury. Mounted patients comprised 77% of the cohort.
      Mounted patients were more likely to sustain upper limb fractures or spinal
      injuries, and more likely to wear helmets. Unmounted were more likely to be
      younger males, and more likely to sustain facial or abdominal injuries.
      Strikingly, unmounted children had significantly more severe and critical Injury
      Severity Scores (OR 2.6; 95% CI 1.5, 4.6) and longer hospital stay (2.0days vs
      1.1days; p<0.001). Unmounted patients were twice as likely to require intensive
      care or surgery, and eight times more likely to sustain a severe head injury.
      CONCLUSIONS: Horse-related injuries in children are serious. Unmounted patients
      are distinct from mounted patients in terms of gender, age, likelihood of
      personal protective equipment use, severity of injuries, and requirement for
      intensive or invasive care. This study highlights the importance of vigilance and
      other safety behaviours when unmounted and around horses, and proposes specific
      targets for future injury prevention campaigns, both in setting of organised and
      private equestrian activity.

PMID- 29224907
TI  - Quantitative Postural Analysis of Children With Congenital Visual Impairment.
AB  - OBJECTIVES: The aim of this study was to compare the postural alignment of
      children with visual impairment with that of children without visual impairment.
      METHODS: The sample studied was 74 children of both sexes ages 5 to 12 years. Of
      these, 34 had visual impairment and 40 were control children. Digital photos from
      the standing position were used to analyze posture. Postural variables, such as
      tilt of the head, shoulder position, scapula position, lateral deviation of the
      spine, ankle position in the frontal plane and head posture, angle of thoracic
      kyphosis, angle of lumbar lordosis, pelvis position, and knee position in the
      frontal and sagittal planes, were measured with the Postural Assessment Software
      0.63, version 36 (SAPO, Sao Paulo, Brazil), with markers placed in predetermined
      bony landmarks. RESULTS: The main results of this study showed that children with
      visual impairment have increased head tilt (P < .001), shoulder deviation in
      frontal plane (P = .004), lateral deviation of the spine (P < .001), changes in
      scapula position (P = .012), higher thoracic kyphosis (P = .004), and lower
      lumbar lordosis (P < .001). CONCLUSIONS: Visual impairment influences postural
      alignment. Children with visual impairment had increased head tilt, uneven
      shoulders, greater lateral deviation of the spine, thoracic kyphosis, lower
      lumbar lordosis, and more severe valgus deformities on knees.

PMID- 29224908
TI  - Mortality hospital of nonagenarian patients in Internal Medicine.
AB  - OBJECTIVES: To describe the predictors of hospital mortality in nonagenarian
      patients. PATIENTS AND METHOD: We retrospectively studied 421 patients aged 90
      years or older hospitalised in a department of internal medicine. Using logistic
      regression, we analysed the association between demographic, clinical and
      functional parameters and hospital mortality. RESULTS: The mean age was 92.5
      years (SD+/-2.5), and 265 (62.9%) of the patients were women. The main diagnoses
      were infectious diseases (257 patients, 61%) and heart failure (183, 43.5%), and
      the mean stay was 11.9 days (SD+/-8.6). During the hospitalisation, 96 patients
      died (22.8%). The predictors of mortality were age (P=.002), functional state
      (P=.006), comorbidity (P=.018) and diagnoses of pneumonia (P=.001), sepsis
      (P=.012) and respiratory failure (P<.001). CONCLUSION: The hospital mortality of
      nonagenarian patients treated in internal medicine exceeds 20% and is associated
      with pneumonia, comorbidity burden and functional impairment.

PMID- 29224909
TI  - Hygiene Hypothesis in Asthma Development: Is Hygiene to Blame?
AB  - Industrialized countries have registered epidemic rates on allergic diseases,
      such as hay fever, asthma, eczema, and food allergies. The Hygiene Hypothesis was
      born from work made by Dr. David Strachan, who observed that younger siblings
      were less susceptible to eczema and asthma, and proposed that this was a result
      of increased transmission of infectious agents via unhygienic practices within a
      household. This initial hypothesis was then reframed as the old
      friends/microbiota hypothesis, implicating non-pathogenic commensal
      microorganisms as the source of immunomodulatory signals necessary to prevent
      immune-mediated chronic disorders. Although the hygiene hypothesis is supported
      by epidemiological research of allergic diseases in certain industrialized
      settings, it often fails to explain the incidence of asthma in less affluent
      regions of the world. In this review, we summarize up-to-date information on
      genetic and environmental factors associated with asthma in different human
      populations, and present evidence that calls for caution when associating hygiene
      with the pathogenesis of asthma and other allergic conditions.

PMID- 29224910
TI  - Regulation of SIRT3/FOXO1 Signaling Pathway in Rats with Non-alcoholic
      Steatohepatitis by Salvianolic Acid B.
AB  - AIMS: To explore the effect of salvianolic acid B (Sal B) on regulation of
      SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis (NASH).
      METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into control, model
      and treatment groups. After 12 weeks of successful model establishment with high
      fat diet, treatment group was given Sal B by intragastric administration. After
      12 weeks of treatment, rats were sacrificed and livers were taken to test
      indicators such as liver index, TG, TC, ALT, AST, reactive oxygen species (ROS)
      by DCFH-DA probe, SOD2 activity by WST-8 test. mRNA and protein expression of
      SIRT3, SOD2, catalase were detected by real time PCR and western blot,
      respectively. The acetylation level of FOXO1 and SOD2 was detected by immuno
      precipitation (IP). RESULT: Liver index, ALT, AST, TG, TC, and ROS of model group
      were higher than those of control and treatment groups, which the difference was
      statistically significant (p <0.01). SOD2 activity of model group was lower than
      that of control and treatment groups. In treatment group, HE staining and
      electron microscopy showed hepatic tissue pathological change and mitochondrial
      structure damage alleviate. mRNA and protein expression of SIRT3, SOD2, catalase
      were lower in model group and the difference was statistically significant (p
      <0.05), which was opposite in the acetylation level of FOXO1 and SOD2 by IP.
      CONCLUSION: Sal B can decrease oxidative stress reaction by regulating
      SIRT3/FOXO1 signaling pathway and play a therapeutic role in the treatment of
      NASH in rats.

PMID- 29224911
TI  - The hands and head of a surgeon: Modeling operative competency with multimodal
      epistemic network analysis.
AB  - BACKGROUND: This paper explores a method for assessing intraoperative performance
      by modeling how surgeons integrate psychomotor, procedural, and cognitive skills
      to manage errors. METHODS: Audio-video data were collected from general surgery
      residents (N = 45) performing a simulated laparoscopic ventral hernia repair.
      Errors were identified using a standard checklist, and speech was coded for
      elements related to error recognition and management. Epistemic network analysis
      (ENA) was used to model the integration of error management skills. RESULTS:
      There was no correlation between number or type of errors committed and operative
      outcome. However, ENA models showed significant differences in the integration of
      error management skills between high-performing and low-performing residents.
      CONCLUSION: These results suggest that error checklists and surgeons' speech can
      be used to model the integration of psychomotor, procedural, and cognitive
      aspects of intraoperative performance. Moreover, ENA can identify and quantify
      this integration, providing insight on performance gaps in both individuals and
      populations.

PMID- 29224912
TI  - Response to Claire Vale, David Fisher, Jayne Tierney, Ian White, Matthew Sydes,
      and James Carpenter's Letter to the Editor re: Christopher J.D. Wallis, Zachary
      Klaassen, Bimal Bhindi, et al. Comparison of Abiraterone Acetate and Docetaxel
      with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naive
      Prostate Cancer: A Systematic Review and Network Meta-analysis. Eur Urol. In
      press. https://doi.org/10.1016/j.eururo.2017.10.002.

PMID- 29224913
TI  - Re: Is Preoperative Assessment and Treatment of Asymptomatic Bacteriuria
      Necessary for Reducing the Risk of Postoperative Symptomatic Urinary Tract
      Infection After Urologic Surgical Procedures?

PMID- 29224914
TI  - Nodal Metastases at Radical Prostatectomy: More Aggressive Disease Warrants
      Consideration of Multimodal Treatment.

PMID- 29224915
TI  - Re: Active Surveillance for Low-risk Nonmuscle Invasive Bladder Cancer (NMIBC): a
      Confirmatory and Resource Consumption Study from Bladder Cancer Italian Active
      Surveillance (BIAS) Project.

PMID- 29224916
TI  - Cancer Radiosensitizers.
AB  - Radiotherapy (RT) is a mainstay treatment for many types of cancer, although it
      is still a large challenge to enhance radiation damage to tumor tissue and reduce
      side effects to healthy tissue. Radiosensitizers are promising agents that
      enhance injury to tumor tissue by accelerating DNA damage and producing free
      radicals. Several strategies have been exploited to develop highly effective and
      low-toxicity radiosensitizers. In this review, we highlight recent progress on
      radiosensitizers, including small molecules, macromolecules, and nanomaterials.
      First, small molecules are reviewed based on free radicals, pseudosubstrates, and
      other mechanisms. Second, nanomaterials, such as nanometallic materials,
      especially gold-based materials that have flexible surface engineering and
      favorable kinetic properties, have emerged as promising radiosensitizers.
      Finally, emerging macromolecules have shown significant advantages in RT because
      these molecules can be combined with biological therapy as well as drug delivery.
      Further research on the mechanisms of radioresistance and multidisciplinary
      approaches will accelerate the development of radiosensitizers.

PMID- 29224917
TI  - Ectopic Intrathoracic Liver Tissue.

PMID- 29224918
TI  - The regulatory network behind MHC class I expression.
AB  - The MHC class I pathway, presenting endogenously derived peptides to T
      lymphocytes, is hijacked in many pathological conditions. This affects MHC class
      I levels and peptide presentation at the cell surface leading to immune escape of
      cancer cells or microbes. It is therefore important to identify the molecular
      mechanisms behind MHC class I expression, processing and antigen presentation.
      The identification of NLRC5 as regulator of MHC class I transcription was a huge
      step forward in understanding the transcriptional mechanism involved.
      Nevertheless, many questions concerning MHC class I transcription are yet
      unsolved. Here we illuminate current knowledge on MHC class I and NLRC5
      transcription, we highlight some remaining questions and discuss the use of
      quickly developing high-content screening tools to reveal unknowns in MHC class I
      transcription in the near future.

PMID- 29224919
TI  - Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion
      and Addiction-Related Surveillance System.
AB  - : Tapentadol, a Schedule II opioid with a combination of u-opioid activity and
      norepinephrine reuptake inhibition, is used for the management of moderate to
      severe acute and chronic pain. Its dual mechanism of action is thought to reduce
      opioid-related side effects that can complicate pain management. Since approval,
      tapentadol has been tracked across multiple outcomes suggesting abuse liability,
      and a pattern of relatively low, although not absent, abuse liability has been
      found. This retrospective cohort study further details the abuse liability of
      tapentadol as an active pharmaceutical ingredient (API) when immediate-release as
      well as extended-release formulations were on the market together (fourth quarter
      of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol,
      hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison
      Center, Drug Diversion, and Treatment Center Programs Combined data streams from
      the Researched Abuse, Diversion and Addiction-Related Surveillance system.
      Findings suggest the public health burden related to tapentadol to date is low,
      but present. Event rates of abuse per population-level denominators were
      significantly lower than all other opioids examined. However, when adjusted for
      drug availability, event rates of abuse were lower than most Schedule II opioids
      studied, but were not the lowest. Disentangling these 2 sets of findings further
      by examining various opioid formulations, such as extended-release and the role
      of abuse-deterrent formulations, is warranted. PERSPECTIVE: This article presents
      the results from an examination of tapentadol API across the Researched Abuse,
      Diversion and Addiction-Related Surveillance System: a broad and carefully
      designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion,
      and Treatment Centers combined suggest a low, but present public health burden
      related to tapentadol.

PMID- 29224920
TI  - [Pharmaceutical cognitive doping in students: a chimeric way to get-a-head?]
AB  - For students, the pressing demands for memorization, top-level performance, and
      peer competition create an environment favorable for pharmaceutical cognitive
      doping behavior. We aimed to describe recent practices and the benefit / risk
      ratio of such behavior and to discuss the issues at stake. The prevalence of
      pharmaceutical cognitive doping among students has been reported from 1.3% to 33%
      across studies, with variations depending on country and definition of
      pharmaceutical cognitive doping. The therapeutic classes most frequently cited as
      being diverted for doping purposes are psychostimulants and nootropics
      (methylphenidate, modafinil, piracetam), corticosteroids, sedative drugs and beta
      blockers. Some illegal substances such as cannabis, amphetamines and cocaine are
      also consumed in order to boost mental function. Finally, over-the-counter
      products, such as caffeine-based tablets or energy drinks, or alcohol, are also
      widely used by students whose motivations involve enhanced performance,
      concentration, memory, and staying awake during the revision and exam period.
      However, the expected (often fantasized) effectiveness of these products does not
      correspond to the reality of a modest controversial impact on cognitive
      performance. There appears to be an emerging profile of the student more inclined
      to doping behavior. Cognitive doping thus raises the question of its regulation,
      opening a debate opposing, on one hand, individual freedom and supposed
      collective benefits and, on the other hand, health consequences, educational
      (in)equality, and the risk of tarnished academic success. Strengthening school
      and university medicine, through prevention campaigns and the identification of
      subjects at risk, is essential to limit the extent, risk, and damages associated
      with such practices.

PMID- 29224921
TI  - Effects of acrylamide on oxidant/antioxidant parameters and CYP2E1 expression in
      rat pancreatic endocrine cells.
AB  - Oxidative stress is one of the principle mechanism of acrylamide-induced
      toxicity. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to
      glycidamide or by direct conjugation with glutathione. Bearing in mind that up to
      now the effects of acrylamide on oxidative stress status and CYP2E1 level in
      endocrine pancreas have not been studied we performed qualitative and
      quantitative immunohistochemical evaluation of inducible nitric oxide synthase
      (iNOS), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase
      (CAT) and CYP2E1 expression in islets of Langerhans of rats subchronically
      treated with 25 or 50mg/kg bw of acrylamide. Since the majority of cells (>80%)
      in rodent islets are beta cells, in parallel studies, we employed the Rin-5F beta
      cell line to examine effects of acrylamide on redox status and the activity of
      CAT, SOD and glutathione-S-transferase (GST), their gene expression, and CYP2E1,
      NF-E2 p45-related factor 2 (Nrf2) and iNOS expression. Immunohistochemically
      stained pancreatic sections revealed that acrylamide induced increase of iNOS and
      decrease of CYP2E1 protein expression, while expression of antioxidant enzymes
      was not significantly affected by acrylamide in islets of Langerhans. Analysis of
      Mallory-Azan stained pancreatic sections revealed increased diameter of blood
      vessels lumen in pancreatic islets of acrylamide-treated rats. Increase in the
      GST activity, lipid peroxidation and nitrite level, and decrease in GSH content,
      CAT and SOD activities was observed in acrylamide-exposed Rin-5F cells. Level of
      mRNA was increased for iNOS, SOD1 and SOD2, and decreased for GSTP1, Nrf2 and
      CYP2E1 in acrylamide-treated Rin-5F cells. This is the first report of the
      effects of acrylamide on oxidant/antioxidant parameters and CYP2E1 expression in
      pancreatic endocrine cells.

PMID- 29224922
TI  - Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express
      connexin 36.
AB  - Previous studies have shown that following peripheral nerve injury there was a
      downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord;
      however, it is not known whether Cx36 protein is expressed in the dorsal root
      ganglia (DRGs), nor if its levels are altered following peripheral nerve
      injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA
      was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using
      immunohistochemistry (IHC) and immunofluorescence (IF). Double staining revealed
      that Cx36 co-localizes with both anti-beta-III tubulin, a neuronal marker, and
      anti-glutamine synthetase, a satellite glial cell (SGC) marker. In neurons, Cx36
      staining was mostly uniform in somata and fibers of all sizes and its intensity
      increased at the cell membranes. This labeling pattern was in contrast with Cx36
      IF dots mainly found at junctional membranes in islet beta cells used as a
      control tissue. Co-staining with anti-Cx43 and anti-Cx36 showed that whereas
      mostly uniform staining of Cx36 was found throughout neurons and SGCs, Cx43 IF
      puncta were localized to SGCs. Cx36 mRNA was expressed in normal lumbar DRG, and
      it was significantly down-regulated in L4 DRG of rats that underwent sciatic
      nerve injury resulting in persistent hypersensitivity. Collectively, these
      findings demonstrated that neurons and SGCs express Cx36 protein in normal DRG,
      and suggested that perturbation of Cx36 levels may contribute to chronic
      neuropathic pain resulting from a peripheral nerve injury.

PMID- 29224923
TI  - Allele-specific methylation of type 1 diabetes susceptibility genes.
AB  - The susceptibility to autoimmune diseases is influenced by genes encoding major
      histocompatibility complex (MHC) proteins. By examining the epigenetic
      methylation maps of cord blood samples, we found marked differences in the
      methylation status of CpG sites within the MHC genes (cis-metQTLs) between
      carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201
      (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were
      found in children and adults, and were accompanied by reduced HLA-DR protein
      expression in immune cells with the HLA-DR3-DQ2 haplotype. Extensive cis-metQTLs
      were identified in all 45 immune and non-immune type 1 diabetes susceptibility
      genes analyzed in this study. We observed and validated a novel association
      between the methylation status of CpG sites within the LDHC gene and the
      development of insulin autoantibodies in early childhood in children who are
      carriers of the highest type 1 diabetes risk genotype. Functionally relevant
      epigenetic changes in susceptibility genes may represent therapeutic targets for
      type 1 diabetes.

PMID- 29224924
TI  - Prevalence of spontaneous Brugada ECG pattern recorded at standard intercostal
      leads: A meta-analysis.
AB  - OBJECTIVE: Typical Brugada ECG pattern is the keystone in the diagnosis of
      Brugada syndrome. However, the exact prevalence remains unclear, especially in
      Asia. The present study was designed to systematically evaluate the prevalence of
      spontaneous Brugada ECG pattern recorded at standard leads. METHODS: We searched
      the Medline, Embase and Chinese National Knowledge Infrastructure (CNKI) for
      studies of the prevalence of Brugada ECG pattern, published between Jan 1, 2003,
      and September 1, 2016. Pooled prevalence of type 1 and type 2-3 Brugada ECG
      pattern were estimated in a random-effects model, and group prevalence data by
      the characteristic of studies. Meta-regression analyses were performed to explore
      the potential sources of heterogeneity, and sensitivity analyses were conducted
      to assess the effect of each study on the overall prevalence. RESULTS: Thirty
      nine eligible studies involving 558,689 subjects were identified. Pooled
      prevalence of type 1 and 2-3 Brugada ECG pattern was 0.03% (95%CI, 0.01%-0.06%),
      and 0.42% (95%CI, 0.28%-0.59%), respectively. Regions, sample size, year of
      publication were the main source of heterogeneity. The prevalence of type 1
      Brugada ECG pattern was higher in male, Asia, adult, patient, and fever subjects;
      but the relation between fever and type 2-3 Brugada ECG pattern was not
      significant. Sensitivity analysis showed that each study did not lonely affect
      the prevalence of type 1 and type 2-3 Brugada ECG pattern. CONCLUSION: Brugada
      ECG pattern is not rare, especially preponderant in adult Asian males, and fever
      subjects. Clinical screening and further examination of Brugada syndrome in
      potential population need to be highlighted.

PMID- 29224925
TI  - Incidence and clinical characteristics of sudden cardiac death in adult
      congenital heart disease.
AB  - BACKGROUND: The life expectancy of adults with congenital heart disease (CHD) has
      significantly improved in recent decades, with non-cardiovascular causes of death
      now competing with traditional cardiovascular causes. The risk of sudden cardiac
      death (SCD), a devastating event, still remains elevated above that of the
      general population. METHODS: We reviewed 2935 patients in our adult CHD database
      (age>=16years, seen at least once in our centre) and documented all cases of SCD
      between 2000-2015. Incidence and characteristics of SCD cases by congenital
      defect and complexity of disease were determined. RESULTS: We documented 35 cases
      of SCD, with an incidence of 0.4 deaths/1000patientyears (py). Incidence in
      simple, moderate and complex congenital categories was 0.04/1000py, 0.57/1000py
      and 2.0/1000py respectively. The highest risk category was Eisenmenger syndrome,
      with an incidence of 4.8 deaths/1000py. Moderate risk lesions included
      transposition of the great arteries (atrial switch surgery or congenitally
      corrected) and Fontan circulations. Repaired tetralogy, atrial septal defect and
      left ventricular outflow tract lesions were all relatively low risk. We observed
      a high prevalence of atrial arrhythmias (43%) and QRS prolongation (mean 132ms)
      in our SCD cases. CONCLUSIONS: The adult CHD population remains at an elevated
      risk for SCD, particularly in the setting of complex underlying defects. Moderate
      to high risk lesions include Eisenmenger syndrome, transposition of the great
      arteries (atrial switch or congenitally corrected) and Fontan circulations.

PMID- 29224926
TI  - Fully Automated Detection and Quantification of Macular Fluid in OCT Using Deep
      Learning.
AB  - PURPOSE: Development and validation of a fully automated method to detect and
      quantify macular fluid in conventional OCT images. DESIGN: Development of a
      diagnostic modality. PARTICIPANTS: The clinical dataset for fluid detection
      consisted of 1200 OCT volumes of patients with neovascular age-related macular
      degeneration (AMD, n = 400), diabetic macular edema (DME, n = 400), or retinal
      vein occlusion (RVO, n = 400) acquired with Zeiss Cirrus (Carl Zeiss Meditec,
      Dublin, CA) (n = 600) or Heidelberg Spectralis (Heidelberg Engineering,
      Heidelberg, Germany) (n = 600) OCT devices. METHODS: A method based on deep
      learning to automatically detect and quantify intraretinal cystoid fluid (IRC)
      and subretinal fluid (SRF) was developed. The performance of the algorithm in
      accurately identifying fluid localization and extent was evaluated against a
      manual consensus reading of 2 masked reading center graders. MAIN OUTCOME
      MEASURES: Performance of a fully automated method to accurately detect,
      differentiate, and quantify intraretinal and SRF using area under the receiver
      operating characteristics curves, precision, and recall. RESULTS: The newly
      designed, fully automated diagnostic method based on deep learning achieved
      optimal accuracy for the detection and quantification of IRC for all 3 macular
      pathologies with a mean accuracy (AUC) of 0.94 (range, 0.91-0.97), a mean
      precision of 0.91, and a mean recall of 0.84. The detection and measurement of
      SRF were also highly accurate with an AUC of 0.92 (range, 0.86-0.98), a mean
      precision of 0.61, and a mean recall of 0.81, with superior performance in
      neovascular AMD and RVO compared with DME, which was represented rarely in the
      population studied. High linear correlation was confirmed between automated and
      manual fluid localization and quantification, yielding an average Pearson's
      correlation coefficient of 0.90 for IRC and of 0.96 for SRF. CONCLUSIONS: Deep
      learning in retinal image analysis achieves excellent accuracy for the
      differential detection of retinal fluid types across the most prevalent exudative
      macular diseases and OCT devices. Furthermore, quantification of fluid achieves a
      high level of concordance with manual expert assessment. Fully automated analysis
      of retinal OCT images from clinical routine provides a promising horizon in
      improving accuracy and reliability of retinal diagnosis for research and clinical
      practice in ophthalmology.

PMID- 29224927
TI  - Central Visual Field Damage and Parapapillary Choroidal Microvasculature Dropout
      in Primary Open-Angle Glaucoma.
AB  - PURPOSE: To determine whether microvasculature dropout (MvD) in the parapapillary
      choroid is related to the presence of central visual field defects in primary
      open-angle glaucoma (POAG). DESIGN: Cross-sectional observational study.
      PARTICIPANTS: Thirty-two POAG patients with an initial parafoveal scotoma (IPFS)
      within a 10 degrees  radius in 1 hemifield and 42 POAG patients with an initial
      nasal step (INS) within the nasal periphery outside 10 degrees  of fixation in 1
      hemifield. METHODS: The peripapillary choroidal microvasculature was evaluated on
      en face images obtained using swept-source OCT angiography. Microvasculature
      dropout was defined as a focal sectoral capillary dropout with no visible
      microvascular network identified in the choroidal layer. Factors associated with
      IPFS, compared with INS, were assessed using logistic regression analyses. MAIN
      OUTCOME MEASURES: Factors associated with IPFS rather than INS. RESULTS:
      Microvasculature dropout was observed in 25 of 32 eyes (78.1%) in the IPFS group,
      but in only 1 of 42 eyes (2.4%) in the INS group (P < 0.001). In logistic
      regression analyses, only MvD was a significant factor influencing the presence
      of IPFS. Systemic risk factors such as cold extremities (P = 0.026), migraine (P
      = 0.044), lower mean arterial pressure (P = 0.037), and lower ocular perfusion
      pressure (P = 0.024) were associated significantly with the presence of MvD.
      CONCLUSIONS: The presence of MvD in the parapapillary choroid was a strong
      predictor for IPFS.

PMID- 29224929
TI  - Anaerobic biodegradation of dissolved ethanol in a pilot-scale sand aquifer:
      Variability in plume (redox) biogeochemistry.
AB  - The use of ethanol in alternative fuels has led to contamination of groundwater
      with high concentrations of this easily biodegradable organic compound. Previous
      laboratory and field studies have shown vigorous biodegradation of ethanol
      plumes, with prevalence of reducing conditions and methanogenesis. The objective
      of this study was to further our understanding of the dynamic biogeochemistry
      processes, especially dissolved gas production, that may occur in developing and
      aging plume cores at sites with ethanol or other organic contamination of
      groundwater. The experiment performed involved highly-detailed spatial and
      temporal monitoring of ethanol biodegradation in a 2-dimensional (175cm
      high*525cm long) sand aquifer tank for 330days, with a vertical shift in plume
      position and increased nutrient inputs occurring at ~Day 100. Rapid onset of
      fermentation, denitrification, sulphate-reduction and iron(III)-reduction
      occurred following dissolved ethanol addition, with the eventual widespread
      development of methanogenesis. The detailed observations also demonstrate a redox
      zonation that supports the plume fringe concept, secondary reactions resulting
      from a changing/moving plume, and time lags for the various biodegradation
      processes. Additional highlights include: i) the highest dissolved H2
      concentrations yet reported for groundwater, possibly linked to vigorous
      fermentation in the absence of common terminal electron-acceptors (i.e.,
      dissolved oxygen, nitrate, and sulphate, and iron(III)-minerals) and
      methanogenesis; ii) evidence of phosphorus nutrient limitation, which stalled
      ethanol biodegradation and perhaps delayed the onset of methanogenesis; and iii)
      the occurrence of dissimilatory nitrate reduction to ammonium, which has not been
      reported for ethanol biodegradation to date.

PMID- 29224930
TI  - Transport of dissolved organic matter in Boom Clay: Size effects.
AB  - A coupled experimental-modelling approach was developed to evaluate the effects
      of molecular weight (MW) of dissolved organic matter (DOM) on its transport
      through intact Boom Clay (BC) samples. Natural DOM was sampled in-situ in the BC
      layer. Transport was investigated with percolation experiments on 1.5cm BC
      samples by measuring the outflow MW distribution (MWD) by size exclusion
      chromatography (SEC). A one-dimensional reactive transport model was developed to
      account for retardation, diffusion and entrapment (attachment and/or straining)
      of DOM. These parameters were determined along the MWD by implementing a
      discretisation of DOM into several MW points and modelling the breakthrough of
      each point. The pore throat diameter of BC was determined as 6.6-7.6nm. Below
      this critical size, transport of DOM is MW dependent and two major types of
      transport were identified. Below MW of 2kDa, DOM was neither strongly trapped nor
      strongly retarded. This fraction had an averaged capacity factor of 1.19+/-0.24
      and an apparent dispersion coefficient ranging from 7.5*10-11 to 1.7* 10-11m2/s
      with increasing MW. DOM with MW>2kDa was affected by both retardation and
      straining that increased significantly with increasing MW while apparent
      dispersion coefficients decreased. Values ranging from 1.36 to 19.6 were
      determined for the capacity factor and 3.2*10-11 to 1.0*10-11m2/s for the
      apparent dispersion coefficient for species with 2.2kDa<MW<9.3kDa. Straining
      resulted in an immobilisation of in average 49+/-6% of the injected 9.3kDa
      species. Our findings show that an accurate description of DOM transport requires
      the consideration of the size effects.

PMID- 29224928
TI  - Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with
      Sub-Phenotypes in Age-Related Macular Degeneration.
AB  - PURPOSE: To investigate the association of rare predicted loss-of-function (pLoF)
      variants within age-related macular degeneration (AMD) risk loci and AMD sub
      phenotypes. DESIGN: Case-control study. PARTICIPANTS: Participants of AREDS,
      AREDS2, and Michigan Genomics Initiative. METHODS: Whole genome sequencing data
      were analyzed for rare pLoF variants (frequency <0.1%) in the regions of
      previously identified 52 independent risk variants known to be associated with
      AMD. Frequency of the rare pLoF variants in cases with intermediate or advanced
      AMD was compared with controls. Variants were assigned to the complement,
      extracellular matrix (ECM), lipid, cell survival, immune system, metabolism, or
      unknown/other pathway. Associations of rare pLoF variant pathways with AMD sub
      phenotypes were analyzed using logistic and linear regression, and Cox
      proportional hazards models. MAIN OUTCOME MEASURES: Differences in rare pLoF
      variant pathway burden and association of rare pLoF variant pathways with sub
      phenotypes within the population with AMD were evaluated. RESULTS: Rare pLoF
      variants were found in 298 of 1689 cases (17.6%) and 237 of 1518 controls (15.6%)
      (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.91-1.36; P = 0.310). An
      enrichment of rare pLoF variants in the complement pathway in cases versus
      controls (OR, 2.94; 95% CI, 1.49-5.79; P = 0.002) was observed. Within cases,
      associations between all rare pLoF variants and choroidal neovascularization
      (CNV) (OR, 1.34; 95% CI, 1.04-1.73; P = 0.023), calcified drusen (OR, 1.33; 95%
      CI, 1.04-1.72; P = 0.025), higher scores on the AREDS Extended AMD Severity Scale
      (Standardized Coefficient Beta (beta)=0.346 [0.086-0.605], P = 0.009), and
      progression to advanced disease (hazard ratio, 1.25; 95% CI, 1.01-1.55; P =
      0.042) were observed. At the pathway level, there were associations between the
      complement pathway and geographic atrophy (GA) (OR, 2.17; 95% CI, 1.12-4.24; P =
      0.023), the complement pathway and calcified drusen (OR, 3.75; 95% CI, 1.79-7.86;
      P < 0.001), and the ECM pathway and more severe levels in the AREDS Extended AMD
      Severity Scale (beta = 0.62; 95% CI, 0.04-1.20; P = 0.035). CONCLUSIONS: Rare
      pLoF variants are associated with disease progression. Variants in the complement
      pathway modify the clinical course of AMD and increase the risk of developing
      specific sub-phenotypes.

PMID- 29224932
TI  - Department of Error.

PMID- 29224933
TI  - Improving access to psychological therapies in England.

PMID- 29224931
TI  - Transparency about the outcomes of mental health services (IAPT approach): an
      analysis of public data.
AB  - BACKGROUND: Internationally, the clinical outcomes of routine mental health
      services are rarely recorded or reported; however, an exception is the English
      Improving Access to Psychological Therapies (IAPT) service, which delivers
      psychological therapies recommended by the National Institute for Health and Care
      Excellence for depression and anxiety disorders to more than 537 000 patients in
      the UK each year. A session-by-session outcome monitoring system ensures that
      IAPT obtains symptom scores before and after treatment for 98% of patients.
      Service outcomes can then be reported, along with contextual information, on
      public websites. METHODS: We used publicly available data to identify predictors
      of variability in clinical performance. Using beta regression models, we analysed
      the outcome data released by National Health Service Digital and Public Health
      England for the 2014-15 financial year (April 1, 2014, to March 31, 2015) and
      developed a predictive model of reliable improvement and reliable recovery. We
      then tested whether these predictors were also associated with changes in service
      outcome between 2014-15 and 2015-16. FINDINGS: Five service organisation features
      predicted clinical outcomes in 2014-15. Percentage of cases with a problem
      descriptor, number of treatment sessions, and percentage of referrals treated
      were positively associated with outcome. The time waited to start treatment and
      percentage of appointments missed were negatively associated with outcome.
      Additive odd ratios suggest that moving from the lowest to highest level on an
      organisational factor could improve service outcomes by 11-42%, dependent on the
      factor. Consistent with a causal model, most organisational factors also
      predicted between-year changes in outcome, together accounting for 33% of
      variance in reliable improvement and 22% for reliable recovery. Social
      deprivation was negatively associated with some outcomes, but the effect was
      partly mitigated by the organisational factors. INTERPRETATION: Traditionally,
      efforts to improve mental health outcomes have largely focused on the development
      of new and more effective treatments. Our analyses show that the way
      psychological therapy services are implemented could be similarly important.
      Mental health services elsewhere in the UK and in other countries might benefit
      from adopting IAPT's approach to recording and publicly reporting clinical
      outcomes. FUNDING: Wellcome Trust.

PMID- 29224934
TI  - Department of Error.

PMID- 29224936
TI  - Bilateral Pulmonary Sequestration in a Preterm Infant.

PMID- 29224937
TI  - Gut Transit in Duchenne Muscular Dystrophy Is Not Impaired: A Study Utilizing
      Wireless Motility Capsules.
AB  - We examined gut transit in 7 young adults (18-24 years of age) with Duchenne
      muscular dystrophy using wireless motility capsules. Total and segmental gut
      transit times were normal in essentially all patients. Our study using a
      validated tool suggests normal transit constipation as the pathophysiologic basis
      for constipation in Duchenne muscular dystrophy.

PMID- 29224938
TI  - Subclinical Atherosclerosis in Pediatric Liver Transplant Recipients: Carotid and
      Aorta Intima-Media Thickness and Their Predictors.
AB  - OBJECTIVE: To investigate prevalence and predictors of cardiovascular risk in
      pediatric liver transplant recipients using noninvasive markers of subclinical
      atherosclerosis: carotid intima-media thickness (cIMT) and aorta intima-media
      thickness (aIMT). STUDY DESIGN: Cross-sectional study of 88 pediatric liver
      transplant recipients. The cIMT and aIMT were measured by ultrasound imaging
      using standardized protocol. RESULTS: Participants were 15.4 +/- 4.8 years of
      age, and 11.2 +/- 5.6 years post-transplantation. The cIMT and aIMT were both
      higher in males than females. In analyses adjusted for sex, age, and height, the
      cIMT was higher in subjects transplanted for chronic/cirrhotic liver disease and
      lower in subjects on cyclosporine (n = 9) than tacrolimus (n = 71). The cIMT was
      not associated with rejection history or current corticosteroid use. The cIMT
      increased with increasing diastolic blood pressure and triglycerides. The aIMT (n
      = 83) also increased with age, and its rate of increase post-transplant varied by
      age at transplantation. In adjusted analyses, aIMT was higher in subjects with
      glucose intolerance. In analysis of patients <=20 years of age for whom blood
      pressure percentiles could be calculated (n = 66), aIMT increased with increasing
      diastolic blood pressure percentile (0.010 mm per 5-percentile; 95% CI, 0.000
      0.021; P = 0.05). Neither the cIMT nor the aIMT was associated with obesity,
      systolic hypertension, or other dyslipidemia at study visit. CONCLUSION: Measures
      of long-term cardiovascular risk were associated with conditions that are more
      common in pediatric liver transplant recipients than nontransplanted peers,
      namely, diastolic hypertension and glucose intolerance. Larger, longitudinal
      studies are warranted to investigate whether cIMT could be useful for stratifying
      these patients' cardiovascular risk-and potential need for proactive intervention
      during long-term follow-up.

PMID- 29224935
TI  - Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey
      in Japan.
AB  - OBJECTIVE: To assess the safety and efficacy of infliximab (IFX) for the
      treatment of patients with Kawasaki disease (KD). STUDY DESIGN: This was a
      nationwide survey of 274 Japanese institutions exploring how IFX was used to
      treat patients with KD. The patients' sex, age, treatment course, pre- and post
      IFX therapy blood test results, coronary artery lesions (CALs), and adverse
      events (AEs) were evaluated. RESULTS: We analyzed 434 patients with KD who
      received IFX between March 2005 and November 2014. The median age at onset was 33
      months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all
      cases, IFX was administered as additional treatment. The median days of illness
      at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was
      administered as third-line treatment, and in 106 patients (24.4%), IFX was
      administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered
      to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2
      days, and the white blood cell count, percentage of neutrophils, and serum C
      reactive protein levels significantly decreased (P < .001), although 119 patients
      (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had
      already developed CALs. In patients without CALs before IFX, 31 patients (10.3%)
      newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX
      showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%);
      however, serious AEs were few and reversible. CONCLUSIONS: IFX might be an
      effective and tolerable treatment for refractory KD.

PMID- 29224939
TI  - The association of statin therapy with the primary patency of femoral and
      popliteal artery stents.
AB  - OBJECTIVE: It has long been known that hydroxymethylglutaryl-coenzyme A reductase
      inhibitors (statins) broadly reduce cardiovascular events in patients with
      peripheral vascular disease. It was the goal of this study to determine whether
      there is an association between statin therapy and primary patency after stenting
      of superficial femoral and popliteal arteries. METHODS: The records of all
      patients undergoing primary nitinol stenting of the femoral and popliteal
      arteries at a single institution and by a single surgeon during a 10-year period
      were reviewed. Demographic characteristics of the patients and risk factors were
      identified. TransAtlantic Inter-Society Consensus (TASC II) classifications were
      determined for all stented lesions. Analysis was performed to determine whether
      the use of statins at the time of stent placement was associated with a change in
      rates of primary patency. Loss of primary patency was said to have occurred when
      an intrastent occlusion or a >=70% stenosis was identified by arterial duplex
      ultrasound or angiography. Kaplan-Meier survival curves were plotted, and
      differences between groups were tested by log-rank method. RESULTS: Between 2004
      and 2014, primary femoral or popliteal stenting was performed on 308 limbs in 250
      patients. At the time of intervention, 52.4% of these patients were being treated
      with statin therapy; 137 interventions were done for claudication and 113 for
      critical limb ischemia. Of the lesions treated, 165 were TASC A or B and 85 were
      TASC C or D. Primary patency rates for all stented lesions were 75%, 54%, and 35%
      at 12, 24, and 36 months. The patency rates at 12, 24, and 36 months,
      respectively, were 80%, 55%, and 40% for those taking statins and 68%, 49%, and
      28% for those not taking statins (P = .178). Statin therapy demonstrated a trend
      toward an association with improved primary patency rates in TASC A/B lesions but
      had no association in TASC C/D lesions (TASC A/B, P = .056; TASC C/D, P = .537).
      Statin compliance was found to be 87% at a mean follow-up of 24.1 months.
      CONCLUSIONS: Although the use of statins has been shown to reduce cardiovascular
      morbidity and mortality in patients with peripheral vascular disease, overall
      there is not an association of these drugs with improved primary patency after
      primary stenting of femoral and popliteal artery lesions. However, when limbs are
      stratified for severity, less severe (TASC A/B) lesions demonstrated a trend
      toward a significant association between statin use and improved primary patency.
      This finding was not seen in more severe (TASC C/D) disease.

PMID- 29224940
TI  - Results of nonoperative management of acute limb ischemia in infants.
AB  - OBJECTIVE: Acute limb ischemia (ALI) in infants poses a challenge to the
      clinician secondary to poor operative outcomes, limb loss risk, and lifelong
      morbidity. This retrospective study reviewed a 10-year institutional experience
      with the nonoperative management of ALI in infants. METHODS: Infants (aged <=12
      months) diagnosed with ALI by duplex ultrasound and treated with initial
      nonoperative management at a tertiary care children's hospital were identified
      through vascular laboratory arterial duplex ultrasound records and International
      Classification of Diseases and Current Procedural Terminology codes associated
      with ALI. Demographics of the patients, injury characteristics, treatment
      administered, and outcomes were abstracted by chart review and presented using
      descriptive statistics. RESULTS: During the study period, a total of 25 (28%
      female) infant patients were diagnosed with ALI. The average age for this cohort
      was 3.5 +/- 3.2 months (standard deviation). Most cases were secondary to
      iatrogenic injury (88%) from arterial cannulation. Injury sites were more
      concentrated to the lower extremities (84%) compared with the upper. Absence of
      Doppler signals was noted in 64% of infants, whereas limb cyanosis was observed
      in 60% at the time of presentation. Infants were initially treated with
      anticoagulation (80%) when possible. Two patients failed to respond to
      nonoperative management and required thrombolysis secondary to progression of
      thrombus burden while anticoagulated. There were no major (above-ankle)
      amputations at 30 days. Three deaths occurred within 30 days; all were unrelated
      to limb ischemia. In the 30-day survivors, overall duration of follow-up was 53.5
      +/- 38.5 months. One infant required above-knee amputation 6 weeks after
      diagnosis, resulting in an overall limb salvage rate of 96% on follow-up. Long
      term morbidity included two patients with a chronic wound of the affected limb
      and one patient with limb length discrepancy. No subjects reported claudication
      at the latest follow-up appointment. In addition, all patients were independently
      ambulatory except for one adolescent girl who was using a walker with leg braces.
      CONCLUSIONS: In contrast to the adult population, ALI in infants can be managed
      with anticoagulation alone with good results. Long-term follow-up continues to
      demonstrate excellent functional results and minimal disability.

PMID- 29224941
TI  - Open surgery versus endovascular approach in treatment of extracranial carotid
      artery aneurysms.
AB  - OBJECTIVE: The objective of this study was to investigate and to compare the
      early and long-term results of open surgery with endovascular intervention in the
      treatment of extracranial carotid artery aneurysms (ECCAs). METHODS: A
      retrospective review of patients diagnosed with ECCAs who underwent open surgical
      or endovascular treatment from 1997 to 2017 was performed. Clinical
      characteristics, aneurysm profile, and treatment outcomes were recorded. Early
      results (<30 days) were evaluated in terms of mortality, perioperative stroke or
      transient ischemic attack, and cranial nerve injury. Late results were analyzed
      in terms of both overall and stroke-free survival and freedom from
      reinterventions. RESULTS: A total of 48 patients with ECCAs including 34 (70.8%)
      true aneurysms and 14 (29.2%) pseudoaneurysms were treated. The median age was 51
      years, and 19 patients (39.6%) were men; 41 patients (85.4%) had symptoms,
      whereas 7 (14.6%) were asymptomatic. Among 48 patients, 32 patients (66.7%)
      underwent open surgery; endovascular repair was performed on 16 patients (33.3%).
      The 30-day stroke or transient ischemic attack rate was not significantly
      different between the open group (6.3% [2/32]) and the endovascular group (0%
      [0/16]; P = .307). Cranial nerve injuries occurred in eight patients in the open
      group (25%) and in no patient in the endovascular group (0%; P = .029). Median
      length of stay was significantly longer in the open group than in the
      endovascular group (20 vs 14 days, respectively; P = .013). Median follow-up was
      46 months (range, 0-20 years), and no aneurysm-related death occurred during this
      period. Overall survival rates at 5 years were 88.7% (standard error [SE], 0.08)
      in the open group and 91.7% (SE, 0.08) in the endovascular group (P = .319; log
      rank, .992). For the same time interval, stroke-free survival rates were 85.2%
      (SE, 0.10) in the open group and 92.2% (SE, 0.07) in the endovascular group (P =
      .653; log-rank, .201). One patient (1/28 [3.6%]) in the open group and two
      patients (2/16 [12.5%]) in the endovascular group underwent endovascular
      reinterventions because of restenosis during the follow-up period. Reintervention
      free survival rates were 90.9% in the open group (SE, 0.09) and 69.2% in the
      endovascular group (SE, 0.21; P = .082; log-rank, 3.016). CONCLUSIONS: In this
      single-institutional experience, both operative and endovascular interventions
      for ECCAs provided acceptable early and 5-year results. The endovascular approach
      had significantly less cranial nerve injury and shorter length of hospital stay.

PMID- 29224942
TI  - Fenestrated endovascular aortic aneurysm repair using physician-modified
      endovascular grafts versus company-manufactured devices.
AB  - OBJECTIVE: Fenestrated endografts are customized, patient-specific endovascular
      devices with potential to reduce morbidity and mortality of complex aortic
      aneurysm repair. With approval from the U.S. Food and Drug Administration, our
      center began performing fenestrated endovascular aneurysm repair through a
      physician-sponsored investigational device exemption (IDE #G130210), using both
      physician-modified endografts (PMEGs) and company-manufactured devices (CMDs).
      Because these techniques are associated with specific advantages and
      disadvantages, we sought to investigate differences in outcomes between PMEG and
      CMD cases. METHODS: A single-institution retrospective review of all fenestrated
      endovascular aneurysm repairs was performed. The cohort was analyzed by device
      type (PMEG or CMD) after matching of cases on the basis of (1) number of target
      vessels intended for treatment, (2) extent of aneurysm, (3) aneurysm diameter,
      (4) device configuration, and (5) date of operation. Outcomes of ruptures, common
      iliac artery aneurysms, and aortic arch aneurysms were excluded. Demographics,
      operative details, perioperative complications, length of stay, and
      reinterventions were compared. For patients with >1 year of follow-up time,
      survival, type I or type III endoleak rate, target artery patency, and
      reintervention rate were estimated using the Kaplan-Meier method. RESULTS:
      Between November 30, 2010, and July 30, 2016, 82 patients were identified and
      matched. The cohort included 41 PMEG and 41 CMD patients who underwent repair of
      38 juxtarenal (PMEG, 17; CMD, 21; P = .38), 14 pararenal (PMEG, 6; CMD, 8; P =
      .56), and 30 thoracoabdominal type I to type IV (PMEG, 18; CMD, 12; P = .17)
      aneurysms. There were significant differences in presentation requiring urgent
      aneurysm repair (PMEG, 9; CMD, 0; P = .002), total fluoroscopy time (PMEG, 76
      minutes; CMD, 61 minutes; P = .02), volume of contrast material used (PMEG, 88
      mL; CMD, 70 mL; P = .02), in-operating room to out-of-operating room time (PMEG,
      391 minutes; CMD, 319 minutes; P = .001), incision to surgery end time (PMEG, 276
      minutes; CMD, 224 minutes; P = .002), and 1-year reintervention rate (PMEG, 37%;
      CMD, 13%; log-rank P = .04). No differences in perioperative complications,
      overall length of stay, type I or type III endoleak, or survival were observed
      between PMEG and CMD. For the entire cohort including both PMEG and CMD, the
      overall rate of any 30-day postoperative complication was 39%, and the Kaplan
      Meier estimate of survival at 1 year was 86%. CONCLUSIONS: In this single
      institution experience of fenestrated endovascular aneurysm repair, the primary
      differences between PMEG and CMD related only to operative metrics and the need
      for postoperative reinterventions. No statistically significant advantage was
      found for one approach over the other; we therefore cannot conclude that one
      approach is better than the other. Both remain viable options that may compare
      favorably with open repair of complex aortic aneurysms. Further studies are
      necessary to determine whether this relative equivalence represents a type II
      error or lack of long-term durability data or whether true equivalence between
      PMEG and CMD approaches exists.

PMID- 29224943
TI  - Outcomes after early and delayed carotid endarterectomy in patients with
      symptomatic carotid artery stenosis.
AB  - OBJECTIVE: The objective of this study was to define outcomes after carotid
      endarterectomy (CEA) in patients with symptomatic carotid artery stenosis (CAS)
      when patients are operated on within 14 days after onset of symptoms. METHODS:
      Clinical data of consecutive patients who underwent CEA between 2003 and 2012 for
      symptomatic CAS were reviewed. Patients were classified into group 1, CEA <=14
      days of minor stroke or transient ischemic attack, and group 2, CEA >14 days.
      Primary end point was stroke/death; secondary end points were stroke, death, and
      myocardial infarction. RESULTS: There were 233 patients (32% female; mean age, 72
      +/- 9.1 years) who underwent 238 CEAs. Group 1 included 57 CEAs in 56 patients;
      11 CEAs were performed at 0 to 2 days, 23 at 3 to 7 days, and 23 at 8 to 14 days.
      Group 2 included 181 CEAs in 177 patients. One death (group 2) and five strokes
      (group 1, four; group 2, one) occurred at 30 days (stroke/death, 2.6%), more in
      group 1 vs group 2 (7.1% vs 1.1%; P = .03). In group 1, three strokes occurred
      when the patients were operated on within 2 days (27% [3/11]), more than at 3 to
      7 days (0% [0/22]) or 8 to 14 days (4.3% [1/23]; P = .008). Patients operated on
      between days 3 and 14 had similar stroke/death rate to those operated on after 14
      days (2.2% vs 1.1%; P = .49). Myocardial infarction occurred in six patients
      (2.5%; group 1, 0% [0/57]; group 2, 3.3% [6/177]; P = .34). Median follow-up was
      7.0 years (interquartile range, 4.6-9.9 years). Freedoms from stroke/death were
      similar between groups (hazard ratio [HR], 1.22; 95% confidence interval [CI],
      0.75-1.99; P = .42), 69% for group 1 and 76% for group 2 at 5 years. Age >=80
      years, high surgical risk, and no preoperative P2Y12 antagonist use predicted
      stroke/death. Freedoms from any stroke were similar in groups (HR, 2.46; 95% CI,
      0.95-6.41; P = .06); survivals were also similar (HR, 1.12; 95% CI, 0.67-1.87; P
      = .67) at 5 years. CONCLUSIONS: In this single-center study, CEA in symptomatic
      patients had a 30-day stroke/death rate of 2.6%. Age >=80 years and high surgical
      risk predicted late stroke or death; taking P2Y12 antagonists was associated with
      late stroke. High stroke rates when patients were operated on immediately support
      CEA after 2 days in symptomatic patients with CAS.

PMID- 29224944
TI  - Use of the Wound, Ischemia, foot Infection classification system in hemodialysis
      patients after endovascular treatment for critical limb ischemia.
AB  - OBJECTIVE: The Wound, Ischemia, foot Infection (WIfI) classification system is
      used to predict the amputation risk in patients with critical limb ischemia
      (CLI). The validity of the WIfI classification system for hemodialysis (HD)
      patients with CLI is still unknown. This single-center study evaluated the
      prognostic value of WIfI stages in HD patients with CLI who had been treated with
      endovascular therapy (EVT). METHODS: A retrospective analysis was performed of
      collected data on CLI patients treated with EVT between April 2007 and December
      2015. All patients were classified according to their wound status, ischemia
      index, and extent of foot infection into the following four groups: very low
      risk, low risk, moderate risk, and high risk. Comorbidities and vascular lesions
      in each group were analyzed. The prognostic value of the WIfI classification was
      analyzed on the basis of the wound healing rate and amputation-free survival at 1
      year. RESULTS: This study included 163 consecutive CLI patients who underwent HD
      and successful endovascular intervention. The rate of the high-risk group (36%)
      was the highest among the four groups, and the proportions of very-low-risk, low
      risk, and moderate-risk patients were 10%, 18%, and 34%, respectively. The mean
      follow-up duration was 784 +/- 650 days. The wound healing rates at 1 year were
      92%, 70%, 75%, and 42% in the very-low-risk, low-risk, moderate-risk, and high
      risk groups, respectively (P <.01). A similar trend was observed for the 1-year
      amputation-free survival among the groups (76%, 58%, 61%, and 46%, respectively;
      P = .02). CONCLUSIONS: The WIfI classification system predicted the wound healing
      and amputation risks in a highly selected group of HD patients with CLI treated
      with EVT, with a statistically significant difference between high-risk patients
      and other patients.

PMID- 29224945
TI  - An age-based comparison of fistula location, patency, and maturation for elderly
      renal failure patients.
AB  - OBJECTIVE: Current Kidney Disease Outcomes Quality Initiative guidelines do not
      incorporate age in determining autogenous arteriovenous hemodialysis access
      placement, and the optimal initial configuration in elderly patients remains
      controversial. We compared patency, maturation, survival, and complications
      between several age cohorts (<65 years, 65-79 years, >80 years) to determine
      whether protocols should be modified to account for advanced age. METHODS: All
      patients at two teaching hospitals undergoing a first autogenous arteriovenous
      access creation in either arm between 2007 and 2013 were retrospectively analyzed
      from a prospectively maintained database. Kaplan-Meier survival and Cox hazards
      models were used to compare access patency and risk factors for failure. RESULTS:
      There were 941 autogenous arteriovenous accesses (median follow-up, 23 months;
      range, 0-89 months) eligible for inclusion; 152 (15.3%) accesses were created in
      those >80 years, 397 (42.2%) in those 65 to 79 years, and 392 (41.8%) in those
      <65 years. Primary patencies in patients >80 years, 65 to 79 years, and <65 years
      were 40% +/- 4%, 38% +/- 3%, and 51% +/- 3% at 12 months and 12% +/- 5%, 13% +/-
      3%, and 27% +/- 3% at 36 months (P < .001). Primary assisted patencies were 72%
      +/- 4%, 70% +/- 2%, and 78% +/- 2% at 12 months and 52% +/- 5%, 52% +/- 3%, and
      67% +/- 3% at 36 months (P < .001). Secondary patencies were 72% +/- 4%, 71% +/-
      2%, and 79% +/- 2% at 12 months and 54% +/- 5%, 55% +/- 3%, and 72% +/- 3% at 36
      months (P < .001). Radiocephalic patencies were lowest among older cohorts; in
      those >80 years, 65 to 79 years, and <65 years, they were 65% +/- 7%, 67% +/- 4%,
      and 77% +/- 3% at 12 months and 41% +/- 8%, 51% +/- 5%, and 68% +/- 4% at 36
      months (P = .019). Secondary brachiocephalic access patencies in these cohorts
      were 78% +/- 5%, 80% +/- 3%, and 82% +/- 3% at 12 months and 68% +/- 7%, 66% +/-
      5%, and 77% +/- 4% at 36 months (P = .206). Both the age groups 65 to 79 years
      and >80 years demonstrated superior brachiocephalic vs radiocephalic secondary
      patencies (P = .048 and P = .015, respectively); however, no differences between
      configuration and secondary patency were observed within the cohort <65 years.
      Radiocephalic access maturation failure at 12 and 24 months was 25% +/- 3% and
      29% +/- 4% in those <65 years, 32% +/- 3% and 39% +/- 4% in those 65 to 79 years,
      and 40% +/- 7% and 48% +/- 8% in those >80 years (P = .006). Brachiocephalic
      access maturation failures were 17% +/- 3% and 20% +/- 3% at 12 and 24 months in
      those <65 years, 21% +/- 3% and 25% +/- 4% in those 65 to 79 years, and 18% +/-
      5% and 21% +/- 5% in those >80 years (P = .740). On multivariate analysis,
      coronary disease, female sex, previous ipsilateral or bilateral catheters,
      radiocephalic configuration, and age >65 years were associated with secondary
      patency loss. CONCLUSIONS: Patients aged 65 to 79 years and >80 years had
      inferior primary, primary assisted, and secondary patency and maturation compared
      with those <65 years. When stratified by configuration, radiocephalic accesses
      demonstrated lower patency and maturation compared with brachiocephalic accesses
      for patients aged 65 to 79 years and >80 years and were an independent predictor
      of secondary patency loss.

PMID- 29224946
TI  - Revision Arthroplasty of the Wrist in Patients With Rheumatoid Arthritis, Mean
      Follow-Up 6.6 Years.
AB  - PURPOSE: Management of failed total wrist arthroplasty (TWA) can be challenging;
      surgical treatment options include salvage arthrodesis, revision arthroplasty,
      and resection arthroplasty. There are few studies regarding salvage arthrodesis,
      and revision arthroplasty has been infrequently investigated. The aim of the
      study was to report the outcome after revision arthroplasty of the wrist.
      METHODS: A retrospective cohort of 16 revision TWAs was evaluated between 2003
      and 2016. Data were collected before surgery and 1 and 5 years after surgery. The
      indication for revision arthroplasty was failed TWA. The primary end point was
      implant survival. Secondary outcome measures included visual analog scale (VAS)
      pain scores, range of motion, handgrip strength, and functional scoring with the
      Canadian Occupational Performance Measure (COPM), Patient-Rated Wrist Evaluation
      (PRWE), and Disabilities of the Arm, Shoulder, and Hand (DASH). RESULTS: Mean
      follow-up was 6.6 years. Synthetic bone graft was used in 9 cases, allograft
      corticocancellous bone graft in 1 case, and cement in 6 cases. Of the 16 revision
      TWAs, 4 were re-revised, 1 because of infection, and 3 cases underwent total
      wrist arthrodesis. In the non-re-revised cases, range of motion and grip strength
      was preserved compared with preoperative results. The VAS pain score in activity
      improved, but not significantly, at 1 (median, 1; range, 0-4.5) and 5 years after
      surgery (median, 0) compared with before surgery (median, 5). The COPM
      performance and satisfaction as well as PRWE scores improved significantly at 1
      year (median COPM performance, 4.8; COPM satisfaction, 5.6; and PRWE, 24) and
      improved, but not significantly, at the 5-year follow (median COPM performance,
      4.8; COPM satisfaction, 5.0; and PRWE, 37) in the non-re-revised cases.
      CONCLUSIONS: Revision arthroplasty of the wrist is a valid motion-preserving
      option to wrist arthrodesis in the management of failed TWA. However, the outcome
      is uncertain and as many as 25% require additional surgery. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic IV.

PMID- 29224947
TI  - Functional Outcomes of Compression Plating and Bone Grafting for Operative
      Treatment of Nonunions About the Forearm.
AB  - PURPOSE: To describe one center's experience with nonunion of one or both bones
      of the forearm and report on the functional recovery of patients treated for a
      single- or 2-bone forearm nonunion. METHODS: We performed a retrospective
      analysis of 23 patients who presented to our institution over an 11-year period
      and underwent surgical repair of a forearm nonunion (radius, ulna, or both
      bones). The main outcome measurements included time to union, visual analog scale
      pain scores, range of motion, Short Musculoskeletal Function Assessment scores,
      and postoperative complications. RESULTS: Of the 23 patients, 21 (91.3%) healed
      their nonunion after a single surgical procedure. All patients ultimately healed
      their nonunion; 7 patients were healed at 3-month follow-up, 11 healed at 6-month
      follow-up, and 5 healed at 12-month follow-up. Mean visual analog scale pain
      scores improved considerably from presentation to latest follow-up. The mean
      range of motion at the latest follow-up was as follows: elbow 130.9 degrees 
      flexion-extension arc, forearm 78.5 degrees  pronation/77.8 degrees  supination,
      and wrist 76.1 degrees  palmar flexion/74.3 degrees  dorsiflexion. Mean Short
      Musculoskeletal Function Assessment arm and hand index scores improved
      significantly from baseline to the latest follow-up. Mean Short Musculoskeletal
      Function Assessment function, activity, and bothersome indices demonstrated
      improvement, though this was not statistically significant. Two patients required
      further surgery to achieve osseous union. One patient sustained an iatrogenic
      posterior interosseous nerve palsy, which resolved spontaneously. CONCLUSIONS:
      Repair of forearm nonunion with compression plating and bone grafting provides
      reliable clinical and functional outcomes. Patients treated surgically for
      nonunion of one or both of the forearm bones can expect to heal with the
      potential for considerable improvements in pain and function postoperatively.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 29224948
TI  - A Modified Foot and Ankle Score for Assessing Patient Outcomes After First
      Metatarsophalangeal Arthrodesis.
AB  - First metatarsophalangeal (MTP) arthrodesis is commonly used to treat many end
      stage first MTP diseases. The most widely used scale for measuring the clinical
      outcomes after this procedure, the American Orthopaedic Foot and Ankle Society
      Hallux Metatarsophalangeal-Interphalangeal scale, has not been adequately
      validated and does not measure specific foot functions. Another outcome measure,
      the patient-reported Foot and Ankle Outcome Score (FAOS) has acceptable construct
      validity but poor content validity. The FAOS scale has 42 questions, many of
      which are unrelated to the hallux. We designed a short-form FAOS (sf-FAOS)
      consisting of 11 questions that are more relevant to first MTP arthrodesis. The
      sf-FAOS includes a pain subscale and a function subscale, and the score of each
      subscale ranges from 0 (worst outcome) to 100 (best outcome). Our study has shown
      that the sf-FAOS scale has acceptable validity, reliability, and responsiveness.
      In 21 feet (16 patients) with hallux valgus after >1 year of follow-up, the mean
      sf-FAOS pain score had improved by 44.9 points after surgery (from 51.2 to 96.0;
      p < .001), and the mean sf-FAOS function score had improved by 22.5 points (from
      47.3 to 69.8; p <.001). The improvement in the function score for running and
      jumping was limited.

PMID- 29224949
TI  - Endoscopic Plantar Fasciotomy Through Two Medial Portals for the Treatment of
      Recalcitrant Plantar Fasciopathy.
AB  - Plantar fasciopathy is a common cause of heel pain. Endoscopic plantar fasciotomy
      has the advantage of less surgical trauma and rapid recovery. The aim of the
      present prospective study was to delineate the results of endoscopic plantar
      fascia release through 2 medial portals. The present study included 2 groups. The
      first group included 27 feet in 25 patients that had undergone endoscopic plantar
      fascia release followed up for 19.7 (range 12 to 33) months. The second group,
      the control group, included 20 feet in 16 patients treated conservatively and
      followed up for 16.4 (range 12 to 24) months. The results of endoscopic plantar
      fascia release were superior to the conservative methods. The surgically treated
      group experienced significantly less pain, activity limitations, and gait
      abnormality. The presence of a calcaneal spur had no effect on the final
      postoperative score. In conclusion, endoscopic plantar fascia release through 2
      medial portals is an effective procedure for treatment of resistant plantar
      fasciopathy that fails to respond to conservative management options.

PMID- 29224950
TI  - mRNA, microRNA and lncRNA as novel bladder tumor markers.
AB  - Early detection of bladder cancer (BC) is essential for improvement of the
      patient's prognosis and general survival rates. Current diagnostic methods are
      still limited, so new specific and cost-effective biomarkers are emerging as the
      noninvasive tools in treatment decisions in recurrent BC. Gene expression and
      epigenetic profile can be analysed using quantitative real-time-PCR (qRT-PCR)
      method in urine, blood and tissue. This review provides an update of recent
      findings on BC molecular profile as novel markers in diagnosis and prognosis of
      bladder tumors. We describe mRNA-, microRNA- and lncRNA-based biomarkers involved
      in the BC detection, diagnosis, prediction of recurrence and monitoring after
      treatment.

PMID- 29224951
TI  - Design and synthesis of sulfonamidophenylethylureas as novel cardiac myosin
      activator.
AB  - To optimize the lead urea scaffold 1 and 2 as selective cardiac myosin ATPase
      activator, a series of urea derivatives have been synthesized to explore its
      structure activity relationship. Among them N,N-dimethyl-4-(2-(3-(3
      phenylpropyl)ureido)ethyl)benzenesulfonamide (13, CMA = 91.6%, FS = 17.62%; EF =
      11.55%), N,N-dimethyl-4-(2-(1-methyl-3-(3-phenylpropyl)ureido)ethyl)benzene
      sulfonamide (40, CMA = 52.3%, FS = 38.96%; EF = 24.19%) and N,N-dimethyl-4-(2-(3
      methyl-3-(3-phenylpropyl)ureido)ethyl)benzenesulfonamide (41, CMA = 47.6%, FS =
      23.19%; EF = 15.47%) proved to be efficient to activate the cardiac myosin in
      vitro and in vivo. Further the % change in ventricular cell contractility at 5
      MUM of 13 (47.9 +/- 3.2), 40 (45.5 +/- 2.4) and 41 (63.5 +/- 2.2) showed positive
      inotropic effect in isolated rat ventricular myocytes. The potent compounds 13,
      40, 41 were highly selective for cardiac myosin over skeletal and smooth muscle
      myosin, thus proving them these new urea derivatives is a novel scaffold for
      discovery of cardiac myosin activators for the treatment of systolic heart
      failure.

PMID- 29224952
TI  - MUL+DO: a multicomponent index for the quick diagnosis of peritonitis in
      peritoneal dialysis patients.
AB  - Peritoneal infection is a common problem that has a negative impact on the
      survival of patients and the technique. The early administration of peritoneal
      infection treatment reduces complications. The goal of this study is to propose a
      multicomponent index (MUL+DO) for the quick and efficient diagnosis of peritoneal
      infection. We selected a training cohort of peritoneal effluent samples which
      were analysed by Multistix (r) 10 SG Siemens test strips for leukocyte detection.
      Then, each sample was examined according to the gold standard: number of
      leukocytes, polymorphonuclear percentage and microbiological culture. We
      constructed the MUL+DO index by adding one point to the MULTISTIX [0-1-2-3]
      modified chromatic scale if the patient reported pain. The MUL+DO index ranged
      from 0 to 4. A model validation cohort was then created. MUL+DO was applied to
      each sample and leukocytes and polymorphonuclear percentage were also assessed.
      The training cohort ultimately included 134 samples, 34 of which with infection
      (25.4% [17.6-33.1]). Samples with a MUL+DO value greater than 1 presented a
      sensitivity and specificity of 100%. The validation cohort included 100 samples
      with 16 infections (16% [8.3-23.7]). Assuming a sample with a MUL+DO value
      greater than 1 to be positive, we obtained a sensitivity of 100% and a
      specificity of 95.2%. The MUL+DO index applied to the training cohort showed a
      perfect separation of the positive and negative populations. All positive
      patients presented a score >=2. In the validation cohort, the MUL+DO reported a
      sensitivity of 100% and a specificity of 95.2%.

PMID- 29224953
TI  - Nephropathology and nephrology. The need for a change.

PMID- 29224954
TI  - Reference ranges of thromboelastography in premature neonates? Still a long way
      to go.

PMID- 29224955
TI  - Reference intervals of citrated-native whole blood thromboelastography in
      premature neonates.

PMID- 29224956
TI  - Bidirectional shift of group III metabotropic glutamate receptor-mediated
      synaptic depression in the epileptic hippocampus.
AB  - A common function of group III metabotropic glutamate receptors (mGluRs) located
      at the presynaptic site of a glutamatergic synapse is synaptic depression. Here,
      we studied synaptic depression mediated by group III mGluR activation at Schaffer
      collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3)
      synapses by recording field excitatory postsynaptic potentials in the in vitro
      brain slice preparation. In order to gauge the impact of synaptic depression in
      chronically epileptic tissue, we compared rats after pilocarpine-induced status
      epilepticus (post-SE) with control animals. We observed that synaptic
      transmission at control AC-CA3 synapses was sensitive to the group III mGluR
      agonist L-AP4 (10MUM), while there was no effect of this compound at SC-CA1
      synapses in the same tissue. In contrast, synaptic depression at AC-CA3 synapses
      by L-AP4 was lost in chronically epileptic tissue, and we found a significant
      synaptic depression at SC-CA1 synapses in post-SE tissue by L-AP4 and by the
      mGluR8-selective agonist DCPG. The depression by L-AP4 and DCPG in CA1 was also
      demonstrated in immature control tissue suggesting developmental down-regulation
      of mGluR8 at this synapse as well as re-appearance of this isoform under
      pathological conditions. Quantitative real-time RT-PCR was used to identify mGluR
      isoforms and to assess their transcriptional changes in post-SE tissue. These
      analyses revealed down-regulation of mGluR4 and mGluR6 at AC-CA3 and up
      regulation of mGluR8 at SC-CA1 synapses. We conclude that group III mGluR
      mediated synaptic depression is differentially altered in chronically epileptic
      tissue by a bidirectional shift of the transcriptional level.

PMID- 29224957
TI  - Stuck in a Bind With Phosphate Binders.

PMID- 29224958
TI  - Renal Involvement in Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) Syndrome: A
      Case Report.
AB  - We report a case of a patient who had the mitochondrial cytopathy complex of
      neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome diagnosed at age 11
      years with a biopsy-proven kidney involvement that progressed to end-stage renal
      disease at age 21 years. Mutations of mitochondrial DNA (mtDNA) are maternally
      inherited and lead to mitochondrial cytopathies with predominant neurologic
      manifestations: psychomotor retardation, epilepsy, ataxia, neuropathy, and
      myopathy. Given the ubiquitous nature of mitochondria, cellular dysfunction can
      also appear in tissues with high metabolic turnover; thus, there can be cardiac,
      digestive, ophthalmologic, and kidney complications. Mutations in the MT-ATP6
      gene of mtDNA have been shown to cause NARP syndrome without renal involvement.
      We report a patient who had NARP syndrome diagnosed at age 11 years in whom
      glomerular proteinuria was present very early after diagnosis. Although
      neurologic manifestations were stable over time, he developed worsening
      proteinuria and kidney function. He started dialysis therapy at age 21 years.
      Kidney biopsy confirmed the mitochondrial cytopathy histologically, with abnormal
      mitochondria seen on electron microscopy. The MT-ATP6 gene mutation was detected
      in the kidney biopsy specimen.

PMID- 29224959
TI  - Metabolomics approaches in experimental allergic encephalomyelitis.
AB  - A myelin basic protein (MBP)-induced experimental allergic encephalomyelitis
      (EAE) involves paraplegia due to a reversible thoracolumbar spinal cord
      impairment. The aims of this study were thus to find significant metabolic
      biomarkers of inflammation and identify the site of inflammation in the central
      nervous system (CNS) during the acute signs in of the disease using metabolomics.
      All the EAE samples were associated with higher levels of lactate, ascorbate,
      glucose and amino acids, and decreased level of N-acetyl-aspartate (NAA) compared
      to the control group. A decreased NAA level has been particularly shown in lumbar
      spinal cord in relationship with the clinical signs.

PMID- 29224960
TI  - Persons with secondary progressive and relapsing remitting multiple sclerosis
      reveal different responses of tryptophan metabolism to acute endurance exercise
      and training.
AB  - Disturbances in Tryptophan metabolism play a crucial role in multiple sclerosis
      (MS). Exercise is suspected to counteract the progress of MS and its side
      effects. Current research suggests alterations of Tryptophan metabolism in
      healthy individuals in response to exercise. We investigated the influence of
      acute aerobic exercise and training on Tryptophan metabolism in 57 inpatients
      with relapsing remitting ((RRMS) n=33) and secondary progressive ((SPMS) n=24)
      MS. Serotonin increased after training, whereas the kynurenine pathway was only
      activated in persons with RRMS. Further research is warranted to investigate
      whether these changes are associated with clinical measures (e.g. depressions and
      immune function).

PMID- 29224961
TI  - Effective combination of methylprednisolone and interferon beta-secreting
      mesenchymal stem cells in a model of multiple sclerosis.
AB  - Methylprednisolone (MP) has been recommended as a standard drug in MS therapies.
      We previously demonstrated that IFNbeta-secreting human bone marrow-derived
      mesenchymal stem cells (MSCs-IFNbeta) exert immunomodulatory effects in
      experimental autoimmune encephalomyelitic (EAE) mice. In this study, we evaluated
      whether a combined treatment of MP and MSCs-IFNbeta had enhanced therapeutic
      effects on EAE mice. The combination treatment resulted in enhanced
      immunomodulatory effects, including reduced production of pro-inflammatory
      cytokines and increased production of anti-inflammatory cytokines. Thus, our
      results provide a framework for designing novel experimental protocols to enhance
      the therapeutic effects of existing MS treatments.

PMID- 29224962
TI  - Incidence of invasive pneumococcal disease before and during an era of use of
      three different pneumococcal conjugate vaccines in Quebec.
AB  - BACKGROUND: In Quebec, 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13)
      pneumococcal conjugate vaccines were successively used for the immunization of
      children according to a 2+1 doses schedule. OBJECTIVE: Our aim was to assess the
      impact of this program on the epidemiology of invasive pneumococcal disease (IPD)
      in children and adults. METHODS: Notification and laboratory surveillance data
      were analyzed and the immunization status of IPD cases in children was checked.
      RESULTS: In children < 5 years, the IPD rate decreased from 69/100,000 in 2003 to
      12/100,000 in 2016 (83% reduction). Following PCV7 introduction in 2004, there
      has been a rapid decline in PCV7-type IPD cases and 6A. 7F and 19A serotypes
      emerged but their incidence decreased following PCV10 introduction in 2009 and
      PCV13 in 2011, whereas decrease in serotype 3 IPD was modest. Non-PCV13 types
      increased and represented 79% of cases in 2016. The same pattern was seen in
      adults but replacement was complete and there was no decrease in overall IPD
      rate. In those 65 years and over, PCV13 serotypes represented 28% of cases in
      2016 and 62% were serotypes included in the 23-valent polysaccharide vaccine. Out
      of 10 IPD cases caused by serotype 3 in children vaccinated with PCV13 in 2011
      2016, 6 occurred more than one year following the booster dose, which suggests
      short-term protection. Out of 31 breakthrough 19A cases, 19 occurred in children
      aged between 8 and 14 months who had received the 2 primary PCV13 doses but not
      the toddler booster dose, which suggests a window of susceptibility in a 2+1
      schedule. CONCLUSION: PCVs had a major impact on the IPD rate in children but not
      in adults. Among elderly adults, the proportion of cases caused by serotypes
      included in PCV13 is diminishing year after year but a majority of cases remains
      covered by the 23-valent polysaccharide vaccine.

PMID- 29224963
TI  - Meeting report: Initial World Health Organization consultation on herpes simplex
      virus (HSV) vaccine preferred product characteristics, March 2017.
AB  - The development of vaccines against herpes simplex virus (HSV) is an important
      global goal for sexual and reproductive health. A key priority to advance
      development of HSV vaccines is the definition of preferred product
      characteristics (PPCs), which provide strategic guidance on World Health
      Organization (WHO) preferences for new vaccines, specifically from a low- and
      middle-income country (LMIC) perspective. To start the PPC process for HSV
      vaccines, the WHO convened a global stakeholder consultation in March 2017, to
      define the priority public health needs that should be addressed by HSV vaccines
      and discuss the key considerations for HSV vaccine PPCs, particularly for LMICs.
      Meeting participants outlined an initial set of overarching public health goals
      for HSV vaccines in LMICs, which are: to reduce the acquisition of HIV associated
      with HSV-2 infection in high HIV-prevalence populations and to reduce the burden
      of HSV-associated disease, including mortality and morbidity due to neonatal
      herpes and impacts on sexual and reproductive health. Participants also
      considered the role of prophylactic versus therapeutic vaccines, whether both HSV
      2 and HSV-1 should be targeted, important target populations, and infection and
      disease endpoints for clinical trials. This article summarizes the main
      discussions from the consultation.

PMID- 29224965
TI  - Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in
      formation of pyroglutamate-modified amyloid peptides in vitro.
AB  - Compelling evidence suggests a crucial role of amyloid beta peptides (Abeta(1
      40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of
      Abeta(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is
      expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass
      spectrometry application proved N-terminal cleavage of Abeta(1-40/42) by purified
      dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent
      transformation of resulted Abeta(3-40/42) to pE-Abeta(3-40/42) in QC catalyzed
      glutamate cyclization was manifested. Hence, consecutive conversion of Abeta(1
      40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of
      non-degrading pyroglutamated pE-Abeta(3-40/42), which might accumulate and
      contribute to AD progression. The in vitro acceleration of Abeta(1-40)
      aggregation in the simultaneous presence of DPPIV and QC was shown also.

PMID- 29224964
TI  - One or two doses of live varicella virus-containing vaccines: Efficacy,
      persistence of immune responses, and safety six years after administration in
      healthy children during their second year of life.
AB  - BACKGROUND: This phase III B follow-up of an initial multicenter study
      (NCT00226499) will evaluate the ten-year efficacy of two doses of the combined
      measles-mumps-rubella-varicella vaccine (MMRV) and one dose of the live
      attenuated varicella vaccine (V) versus a measles-mumps-rubella control group
      (MMR) for the prevention of clinical varicella disease. Here we present efficacy
      results for six years post-vaccination. METHODS: In phase A of the study, healthy
      children aged 12-22 months from ten European countries were randomized (3:3:1)
      and received either two doses of MMRV, or one dose of combined MMR and one dose
      of monovalent varicella vaccine (MMR+V), or two doses of the MMR vaccine
      (control), 42 days apart. Vaccine efficacy against all and against moderate or
      severe varicella (confirmed by detection of viral DNA or epidemiological link)
      was assessed from six weeks up to six years post-dose 2 for the MMRV and MMR+V
      groups, and was calculated with 95% confidence intervals (CI). The severity of
      varicella was calculated using the modified Vazquez scale (mild <= 7; moderately
      severe = 8-15; severe >= 16). Herpes zoster cases were also recorded. RESULTS:
      5289 children (MMRV = 2279, mean age = 14.2, standard deviation [SD] = 2.5; MMR+V
      = 2266, mean age = 14.2, SD = 2.4; MMR = 744, mean age = 14.2, SD = 2.5 months)
      were included in the efficacy cohort. 815 varicella cases were confirmed.
      Efficacy of two doses of MMRV against all and against moderate or severe
      varicella was 95.0% (95% CI: 93.6-96.2) and 99.0% (95% CI: 97.7-99.6),
      respectively. Efficacy of one dose of varicella vaccine against all and against
      moderate or severe varicella was 67.0% (95% CI: 61.8-71.4) and 90.3% (95% CI:
      86.9-92.8), respectively. There were four confirmed herpes zoster cases (MMR+V =
      2, MMR = 2), all were mild and three tested positive for the wild-type virus.
      CONCLUSIONS: Two doses of the MMRV vaccine and one dose of the varicella vaccine
      remain efficacious through six years post-vaccination.

PMID- 29224966
TI  - Variations in follicle-diameter deviation and a growth spurt in the dominant
      follicle at deviation in Bos taurus heifers.
AB  - Follicle diameter deviation during a follicular wave in cattle is preceded by a
      common-growth phase and begins with continued growth rate of the future dominant
      follicle (DF or F1) and reduced growth rate of the future largest subordinate
      follicle (SF or F2). Follicle diameters were analyzed daily for wave 1 (n=100)
      and wave 2 (n=91). The beginning of expected deviation was designated day 0 and
      was defined as the day the largest follicle was closest to 8.5mm. Conventional
      classification of deviation (F2>=7.0mm at expected deviation) was more frequent
      (P<0.0001) in wave 1 (59%) than in wave 2 (35%); deviation began abruptly. An F2
      undersized classification (F2<7.0mm at expected deviation) was greater (P<0.0001)
      for wave 2 (40%) than for wave 1 (15%); separation of diameters of F1 and F2
      occurred gradually during the last 2days of the common-growth phase. The growth
      rate of F1 in conventional deviations of wave 1 was greater (P<0.002) on days 0
      to 1 (1.8+/-0.1mm/day) than on days -1 to 0 (1.5+/-0.1mm/day). Several other
      novel growth spurts of F1 were observed in association with deviation including
      during switching of diameter rank between F1 and F2 in each of waves 1 and 2.
      Hypotheses were supported that (1) conventional deviation is more common during
      wave 1 whereas F2-undersized deviation is more common during wave 2 and (2) a
      transient growth spurt occurs in F1 of wave 1 at the beginning of diameter
      deviation.

PMID- 29224967
TI  - Ovarian follicular dynamics and conception rate in Bos indicus cows with
      different antral follicle counts subjected to timed artificial insemination.
AB  - Two experiments in Nelore cows subjected to timed artificial insemination (TAI)
      were designed to compare the influence of the antral follicle count (AFC/AFCs) on
      (1) ovarian follicular dynamics and (2) conception rates. First, multiparous cows
      with high (>=45 follicles; n=43) or low (<=15 follicles; n=32) AFCs were selected
      to undergo a TAI protocol to monitor ovarian follicular dynamics. Second, the
      AFCs of 962 cows also subjected to TAI were determined and classified as groups
      of high (G-high; >=45 follicles; n=194), intermediate (G-intermediate; >=20<=40
      follicles, n=397) or low (G-low; <=15 follicles; n=243) AFCs. In study I, the
      ovarian measurements (diameter, perimeter and area) were greater (P<=0.05) and
      there was a greater consistency in number of antral follicles during the period
      of synchronization for TAI in the high than low group. Effects of the AFC and
      ultrasonic evaluation interval on the follicular diameter were observed
      (P<=0.05); however, there was no interaction (P>0.05). Dominant follicles had
      greater diameters (P<=0.05) in the G-low than in the G-high at D4 (7.3+/-2.2 vs.
      6.2+/-1.4mm, respectively, P=0.06), D8 (11.2+/-1.8 vs. 9.5+/-1.8mm,
      respectively), D9 (12.3+/-1.7 vs. 10.6+/-1.7mm, respectively), and D10 (13.4+/
      1.3 vs. 12.2+/-1.8mm, respectively), as well as greater estimated diameters of
      ovulatory follicles (14.4+/-1.5 vs. 13.4+/-2.1mm, respectively, P=0.08). In study
      II, the cows with fewer AFCs had greater (P<=0.05) conception rates (61.7%) than
      the cows with the intermediate (52.9%) and greater (49.5%) AFCs. Nelore cows with
      fewer AFCs subjected to synchronization of time of ovulation had a larger
      follicular diameter and a greater conception rate than the groups with
      intermediate and a greater AFCs.

PMID- 29224968
TI  - Adjunctive treatment with brexpiprazole and escitalopram reduces behavioral
      stress responses and increase hypothalamic NPY immunoreactivity in a rat model of
      PTSD-like symptoms.
AB  - The study explored effects of brexpiprazole (partial D2/5-HT1A agonist, 5-HT2A
      and alpha1B/2C-adrenoceptor antagonist) in rats exposed to predator scent stress
      (PSS), a proposed model of PTSD-like phenotype. Brexpiprazole (3.0mg/kg, PO),
      escitalopram (5.0mg/kg, IP) and their combination were administered twice daily
      for 14 days, starting 14 days after exposure to PSS or sham-PSS, shortly after a
      situational stress reminder. One day after last treatment behavioral responsivity
      was assessed. Brexpiprazole+escitalopram-treated rats spent more time in open
      arms, entered open arms more often and exhibited a lower anxiety index in the
      elevated plus maze than vehicle-treated, PSS-exposed rats. Adjunct
      brexpiprazole+escitalopram treatment reduced startle amplitude, compared with
      vehicle-treated, PSS-exposed rats. Treatment with either drug alone did not
      attenuate anxiety-like behaviors following PSS exposure. Use of cut-off
      behavioral criteria confirmed that adjunct treatment shifted prevalence of PSS
      exposed rats from extreme towards minimal behavioral responders. One day
      following behavioral tests, brains were prepared for immunohistochemical analysis
      of number of BDNF-positive cells and of NPY-positive cells/fibers. PSS exposure
      decreased BDNF levels in hippocampus, but this was not affected by drug
      treatments. PSS exposure decreased number of NPY positive cells/fibers in
      paraventricular and arcuate nuclei of hypothalamus. Adjunct treatment with
      brexpiprazole+escitalopram increased NPY in PSS- and sham-exposed rats. Treatment
      with brexpiprazole alone had no effects, while treatment with escitalopram alone
      increased NPY in the arcuate nucleus of PSS-exposed rats. In conclusion,
      treatment with brexpiprazole+escitalopram may be an effective intervention for
      the attenuation of PTSD-like stress responses, which in part may be mediated by
      activating NPY function.

PMID- 29224969
TI  - Aberrant development of the asymmetry between hemispheric brain white matter
      networks in autism spectrum disorder.
AB  - Atypical brain asymmetry/lateralization has long been hypothesized for autism
      spectrum disorder (ASD), and this model has been repeatedly supported by various
      neuroimaging studies. Recently, hemispheric network topologies have been found to
      be asymmetric, thereby providing a new avenue for investigating brain asymmetries
      under various conditions. To date, however, how network topological asymmetries
      are altered in ASD remains largely unexplored. To clarify this, the present study
      included ASD individuals from the newly released Autism Brain Imaging Data
      Exchange II database (58 right-handed male ASD individuals aged 5 to 26 years and
      70 age- and IQ-matched typically developing (TD) individuals). Diffusion and
      structural magnetic resonance imaging were used to construct hemispheric white
      matter networks, and graph-theory approaches were applied to quantify topological
      efficiencies for hemispheric networks. Statistical analyses revealed a decreased
      rightward asymmetry of network efficiencies with increasing age in the TD group,
      but not in the ASD group. More specifically, the TD group did not exhibit an age
      related increase in network efficiency in the right hemisphere, but the ASD group
      did. For the left hemisphere, no difference between the groups was observed for
      the developmental trajectory of network efficiencies. Intriguingly, within the
      ASD group, more severe restricted and repetitive behavior in ASD was found to be
      correlated with less rightward asymmetry of network local efficiency. These
      findings provide suggestive evidence of atypical network topological asymmetries
      and offer important insights into the abnormal development of ASD brains.

PMID- 29224970
TI  - Management of conjunctival perforation and late Seidel after XEN(r) surgery.
AB  - CLINICAL CASE: The case concerns a 78 year-old woman with a history of XEN(r)
      surgery, in whom a conjunctival perforation was observed at the implant level at
      18-months of follow-up, for which surgical intervention was decided. During
      surgery a short subconjunctival portion was found (0.5mm). An unsuccessful
      attempt was made to extract it by traction, but the XEN(r) broke easily. Finally,
      it was decided to cut it to scleral level, and suture the conjunctiva. During the
      first week there was a decrease in intraocular pressure (6mmHg), to subsequently
      increase to 25, and deciding to start medical treatment. DISCUSSION: Conjunctival
      exposure of the XEN(r) stent is a rare but potentially serious complication. To
      avoid it, a meticulous surgical technique is important when implanting it. If
      this occurs, it is important to identify the cause. If it is due to a short
      subconjunctival portion, a therapeutic alternative is to cut the implant at this
      level to avoid further complications.

PMID- 29224971
TI  - Biomechanical effects of a mandibular advancement device on the temporomandibular
      joint.
AB  - PURPOSE: Mandibular advancement devices are commonly used in the treatment of
      patients with mild to moderate obstructive sleep apnea (OSA). Designed to
      maintain the mandible in forced protrusion while being worn, mandibular
      advancement devices (MADs) are intended to increase the upper airway during
      sleep, thereby reducing OSA symptoms. Depending on the extent of mandibular
      protrusion, side effects including temporomandibular joint dysfunction are
      frequently reported. These are likely to reduce overall treatment success by
      affecting therapeutic adherence. MATERIAL AND METHODS: To investigate the
      biomechanical effects of an MAD on the temporomandibular joints, we used a
      biomechanical model of the human masticatory system. Alterations to the model
      were applied to mimic the effects of a titratable duoblock MAD. The extent of
      mandibular protrusion was simulated up to 10 mm in steps of 1 mm. Compression and
      shear stresses on the temporomandibular structures were predicted during an open
      close maneuver and in neutral position. RESULTS: As the extent of mandibular
      advancement increased, the mandibular condyle migrated anteriorly until passing
      the articular tubercle. Stress on the temporomandibular joint structures did not
      considerably increase in rest whatever the extent of mandibular advancement.
      However, closure of the jaw required extra muscle force as mandibular advancement
      increased. CONCLUSION: Results from this study suggest that temporomandibular
      dysfunction following MAD wearing might be related to altered muscle dynamics
      rather than changes due to increased stress in the temporomandibular joint
      itself.

PMID- 29224972
TI  - Immunohistochemistry, carcinomas of unknown primary, and incidence rates.
AB  - Pathologists use immunohistochemistry is their day-to-day practices to assist in
      distinguishing site of origin of metastatic carcinomas. Here, the work-up is
      discussed neuroendocrine carcinomas, squamous cell carcinomas and adenocarcinomas
      with particular attention to tumor incident rates and predictive values of the
      best-performing immunohistochemical markers.

PMID- 29224973
TI  - Residual pulmonary embolism as a predictor for recurrence after a first
      unprovoked episode: Results from the REVERSE cohort study.
AB  - BACKGROUND: The optimal duration of oral anticoagulant therapy after a first,
      unprovoked venous thromboembolism is controversial due to tightly balanced risks
      and benefits of indefinite anticoagulation. Risk stratification tools may assist
      in decision making. OBJECTIVES: We sought to determine the relationship between
      residual pulmonary embolism assessed by baseline ventilation-perfusion scan after
      completion of 5-7months of oral anticoagulant therapy and the risk of recurrent
      venous thromboembolism in patients with the first episode of unprovoked pulmonary
      embolism. METHODS: We conducted a multicentre prospective cohort study of
      participants with a first, unprovoked venous thromboembolism enrolled after the
      completion of 5-7months of oral anticoagulation therapy. The participants
      completed a mean 18-month follow-up. Participants with pulmonary embolism had
      baseline ventilation-perfusion scan before discontinuation of oral anticoagulant
      therapy and the percentage of vascular obstruction on baseline ventilation
      perfusion scan was determined. During follow-up after discontinuation of oral
      anticoagulant therapy, all episodes of suspected recurrent venous thromboembolism
      were independently adjudicated with reference to baseline imaging. MEASUREMENTS
      AND MAIN RESULTS: During follow-up, 24 of 239 (10.0%) participants with an index
      event of isolated pulmonary embolism or pulmonary embolism associated with deep
      vein thrombosis and central assessment of percentage of vascular obstruction on
      baseline ventilation-perfusion scan had confirmed recurrent venous
      thromboembolism. As compared to participants with no residual pulmonary embolism
      on baseline ventilation-perfusion scan, the hazard ratio for recurrent venous
      thromboembolism was 2.0 (95% CI 0.5-7.3) for participants with percentage of
      vascular obstruction of 0.1%-4.9%, 2.1 (95% CI 0.5-7.8) for participants with
      percentage vascular obstruction of 5.0%-9.9% and 5.3 (95% CI 1.8-15.4) for
      participants with percentage vascular obstruction greater than or equal to 10%.
      CONCLUSIONS: Residual pulmonary embolism assessed by pulmonary vascular
      obstruction on baseline ventilation-perfusion performed after 5-7months of oral
      anticoagulant therapy for the first episode of unprovoked pulmonary embolism was
      associated with a statistically significant higher risk of subsequent recurrent
      venous thromboembolism. Percentage of pulmonary vascular obstruction assessment
      by ventilation-perfusion scans maybe a useful tool to help guide the duration of
      oral anticoagulant therapy after a first unprovoked pulmonary embolism. TRIAL
      REGISTRATION: Registered at www.clinicaltrials.gov identifier: NCT00261014.

PMID- 29224974
TI  - Evaluation of the potential of pelletized biomass from different municipal solid
      wastes for use as solid fuel.
AB  - Four different municipal solid wastes (dog manure, horse manure, apple pomace
      waste and tea waste) and an industrial by-product (NovoGro) were used to produce
      solid fuel pellets. The mixtures followed a raw material to NovoGro ratio of
      50:1. The pellets diameters varied between 4 and 5 mm, and the average length was
      20 mm. The dog manure, horse manure, apple pomace waste and tea waste pellets
      were denoted as DN, HN, AN and TN, respectively. The combustion characteristics
      of the pelletized fuels were investigated, such as total moisture, ash content,
      calorific value and ash fusion point, etc. The physicochemical properties were
      analyzed by using a number of analytical techniques including X-ray fluorescence
      spectrometry (XRF), X-ray diffraction spectrometry (XRD), scanning electron
      microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The results
      of the mechanical, thermal and morphological properties show that the raw
      materials were effectively combined with the NovoGro binder; furthermore, the DN,
      HN and TN pellets exhibited excellent mechanical and thermal properties,
      including high calorific values (>16.30 MJ/kg), high resistance to mechanical
      shock (>99%), high volatile matter contents, optimal softening temperatures and
      optimal ash contents. However, the high K, Ca, and Si contents of the AN can form
      low-melting-point eutectics, which can cause slagging. Moreover, the AN materials
      had large particle sizes, and high cellulose and hemicellulose contents led to
      high total moistures, low softening temperatures and low calorific values. The AN
      was not suitable for use as a fuel. The results suggested that NG is an effective
      binder for pelletization of biomass and showed the feasibility of using municipal
      solid wastes for energy production.

PMID- 29224975
TI  - Metarhizium alvesii sp. nov.: A new member of the Metarhizium anisopliae species
      complex.
AB  - A strain within the Metarhizium anisopliae species complex was isolated in 2009
      from a soil sample in a banana plantation in the municipality of Quixere,
      Northeastern region of Brazil. Previous studies showed that this insect
      pathogenic strain does not fit with any current taxon within the M. anisopliae
      species complex, as determined by both genomic and by mass spectrometric
      analyses. In the present study, CG1123 (=ARSEF 13308) is shown to be
      morphologically indistinguishable from most species in this cosmopolitan species
      complex, whereas multilocus phylogeny confirmed its uniqueness and supports its
      recognition as a new species, Metarhizium alvesii, in honor of Sergio Batista
      Alves, one of the founders of insect pathology in Brazil.

PMID- 29224976
TI  - Body composition and clinical symptoms in patients with hip or knee
      osteoarthritis: Results from the KHOALA cohort.
AB  - OBJECTIVE: To analyze the associations between body composition, notably low lean
      mass, and clinical symptoms [pain, physical function, quality of life (QoL)] in
      patients with symptomatic hip and/or knee OA. METHODS: Cross-sectional study
      using data from the 3-year follow-up visit of the Knee and Hip OsteoArthritis
      Long-term assessment (KHOALA) cohort. Skeletal muscle and fat mass were measured
      by dual X-ray absorptiometry (DXA). Fat mass index (FMI) was defined as total fat
      mass/height2. Appendicular lean mass was adjusted on body mass index (ALM/BMI),
      and low lean mass was defined according to the definition of FNIH Sarcopenia
      Project recommendations. Pain and function were measured by the WOMAC index and
      QoL by the SF-36. RESULTS: In total, 358 patients underwent DXA (67% women, mean
      [SD] age 63.4 [8.4] years, mean BMI 29.5 [5.6]kg/m2). The visual analog scale (0
      100) pain score was 38.0 [24.7] and 25.4% had hip and 74.6% knee OA. Low lean
      mass and ALM/BMI were associated with impaired QoL and WOMAC scores on bivariate
      analysis (all p <= 0.001) but not on multivariate analysis after adjustment for
      FMI. For patients with normal BMI, mean [SD] WOMAC scores were higher (greater
      impairment) with low lean mass than normal body composition (WOMAC function 33.4
      [23.3] and 24.0 [17.4], p = 0.02), and mean SF-36 physical component score was
      lower (greater impairment) 40.3 [10.2] and (44.3 [8.4], p = 0.04). Among patients
      with obesity, low lean mass had no additional effect. CONCLUSION: For patients
      with OA and normal BMI, QoL and function were more impaired for those with than
      without low lean mass. Conserving muscle mass in people with OA could have
      functional and antalgic benefits especially for those with normal BMI.

PMID- 29224977
TI  - Corrigendum to "Molecular and phylogenetic analyses of Salmonella Gallinarum
      trace the origin and diversification of recent outbreaks of fowl typhoid in
      poultry farms" [Vet. Microbiol. 212 (2017) 80-86].

PMID- 29224978
TI  - Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador: the vector
      Lutzomyia sand flies and reservoir mammals.
AB  - The vector Lutzomyia sand flies and reservoir host mammals of the Leishmania
      parasites, causing the Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru
      and Ecuador were thoroughly reviewed, performing a survey of literatures
      including our unpublished data. The Peruvian L. (V.) peruviana, a principal
      Leishmania species causing Andean-CL in Peru, possessed three Lutzomyia species,
      Lu. peruensis, Lu. verrucarum and Lu. ayacuchensis as vectors, while the
      Ecuadorian L. (L.) mexicana parasite possessed only one species Lu. ayacuchensis
      as the vector. Among these, the Ecuadorian showed a markedly higher rate of
      natural Leishmania infections. However, the monthly and diurnal biting activities
      were mostly similar among these vector species was in both countries, and the
      higher rates of infection (transmission) reported, corresponded to sand fly's
      higher monthly-activity season (rainy season). The Lu. tejadai sand fly
      participated as a vector of a hybrid parasite of L. (V.) braziliensis/L. (V.)
      peruviana in the Peruvian Andes. Dogs were considered to be principal reservoir
      hosts of the L. (V.) peruviana and L. (L.) mexicana parasites in both countries,
      followed by other sylvatic mammals such as Phyllotis andium, Didelphis
      albiventris and Akodon sp. in Peru, and Rattus rattus in Ecuador, but information
      on the reservoir hosts/mammals was extremely poor in both countries. Thus, the
      Peruvian disease form demonstrated more complicated transmission dynamics than
      the Ecuadorian. A brief review was also given to the control of vector and
      reservoirs in the Andes areas. Such information is crucial for future development
      of the control strategies of the disease.

PMID- 29224979
TI  - Perceptions, knowledge, attitudes and practices for the prevention and control of
      lymphatic filariasis in Conakry, Republic of Guinea.
AB  - Little is known about the perceptions, attitudes and practices of lymphatic
      filariasis in Conakry, Republic of Guinea. Yet, such knowledge is important for
      an optimal design and implementation of setting-specific prevention and control
      measures. We conducted a cross-sectional study using a mixed methods approach.
      Qualitative data related to people's general experience with lymphatic
      filariasis, their perception of the causes of the disease, the onset of
      elephantiasis, care-seeking behaviour and the socioeconomic impact of lymphatic
      filariasis were collected through in-depth interviews with 85 respondents.
      Quantitative data related to strategies for prevention and the knowledge of the
      causes of the disease were collected by interviewing 429 people. A total of 514
      individuals (313 females and 201 males), aged 10-84 years, participated. Most
      participants were well aware of lymphatic filariasis and they recognized the
      disease mainly by its disfiguring manifestation, collectively termed
      "elephantiasis" or "leg-swelling disease". Morbidity patterns due to filarial
      infection showed an increase with age (from 30 to 50 years) independent of sex.
      Most patients with lymphatic filariasis abandoned their jobs (73.9%) or sought
      other work (21.7%). The main perceived causes of acquiring lymphatic filariasis
      were of supernatural origin (as stated by 8.7% of patients and 5.7% of healthy
      subjects), while mosquito bites were mentioned by fewer participants (4.3% of
      patients and 4.2% of healthy subjects). A number of other causes were reported
      that relate to both medical and non-medical conceptions. The study also
      identified socioeconomic impairments and stigmatization due to elephantiasis.
      Taken together, community perception of lymphatic filariasis in Conakry is
      influenced by sociocultural conceptions. Appropriate health education campaigns
      aimed at enhancing community understanding of the transmission of lymphatic
      filariasis are required to increase the success of mass drug administration
      implemented for the elimination of this disease. There is a need for a morbidity
      management programme to alleviate lymphatic filariasis-related physical and
      emotional burden in Conakry.

PMID- 29224980
TI  - Factors responsible for the post-slaughter loss of carcass and offal's in
      abattoirs in South Africa.
AB  - Global demand for food is surging upward due to the expansion of human
      population. Hence food production and supply need to double with little or no
      waste to meet this demand. Food loss at any point in the farm to fork chain
      inhibits the stability of food security at household and national level. A
      retrospective (AR) and a post mortem meat inspection (PMMI) study to identify
      major causes of offal and carcass condemnation was conducted in three abattoirs
      namely, Adeliade, Queenstown and East London abattoirs represented as AD, QT, and
      EL respectively. The retrospective study revealed the main causes of tongue
      condemnation as abscess (0.08%, 0.03% and 0.05%) and actinobacillosis (0.02%, 0%
      and 0.02%) respectively. The spleen was condemned due to abscess (0.35%, 0.94%
      and 0.17%) and splenomegaly (0.21%, 0.55% and 0.2%). The heart was condemned due
      to cyst (0.24%, 0.36% and 0.2%) and inflammation (0.9%, 1.85%, and 0.75%). While
      the kidney, was condemned due to cyst (0.08%, 0.23% and 0.16%) and nephritis
      (0.94%, 1.01% and 1.18%). However, a greater percentage of condemnation was
      recorded during the active abattoir study. During the same period, partial
      carcass condemnations were mainly due to bruises (63.3%, 50.4% and 41.0%),
      abscess (7%, 6% and 14%) and improper evisceration (19%, 31% and 27%). The
      combined monetary loss due to offal's and carcass condemnation during the AR and
      PMMI study was estimated as ZAR 255194.4 (34191.5 USD) and ZAR 25958.8 (2570.2
      USD) respectively. This study identified major causes of offals and carcass
      condemnation as abscess, bruises, actinobacillosis, cyst, inflammatory conditions
      and improper evisceration. It can be used as starting point information for early
      warning on livestock diseases of economic loss in South Africa.

PMID- 29224981
TI  - Visuomotor mental rotation of a saccade: The contingent negative variation scales
      to the angle of rotation.
AB  - The visuomotor mental rotation (VMR) of a saccade requires a response to a region
      of space that is dissociated from a stimulus by a pre-specified angle, and work
      has shown a monotonic increase in reaction times as a function of increasing
      oblique angles of rotation. These results have been taken as evidence of a
      continuous process of rotation and have generated competing hypotheses. One
      hypothesis asserts that rotation is mediated via frontoparietal structures,
      whereas a second states that a continuous shift in the activity of direction
      specific neurons in the superior colliculus (SC) supports rotation. Research to
      date, however, has not examined the neural mechanisms underlying VMR saccades and
      both hypotheses therefore remain untested. The present study measured the
      behavioural data and event-related brain potentials (ERP) of standard (i.e., 0
      degrees  of rotation) and VMR saccades involving 35 degrees , 70 degrees  and 105
      degrees  of rotation. Behavioural results showed that participants adhered to
      task-based rotation demands and ERP findings showed that the amplitude of the
      contingent negative variation (CNV) linearly decreased with increasing angle of
      rotation. The cortical generators of the CNV are linked to frontoparietal
      structures supporting movement preparation. Although our ERP design does not
      allow us to exclude a possible role of the SC in the rotation of a VMR saccade,
      they do demonstrate that such actions are supported by a continuous and
      cortically based rotation process.

PMID- 29224982
TI  - Perceptual learning induces changes in early and late visual evoked potentials.
AB  - Studies of visual cortical responses following visual perceptual learning (VPL)
      have produced diverse results, revealing neural changes in early and/or higher
      level visual cortex as well as changes in regions responsible for higher
      cognitive processes such as attentional control. In this study, we investigated
      substrates of VPL in the human brain by recording visual evoked potentials with
      high-density electroencephalography (hdEEG) before (Session 1) and after (Session
      2) training on a texture discrimination task (TDT), with two full nights of sleep
      between sessions. We studied the following event-related potential (ERP)
      components: C1 (early sensory processing), P1 and N1 (later sensory processing,
      modulated by top-down spatial attention), and P3 (cognitive processing). Our
      results showed a significant decrease in C1 amplitude at Session 2 relative to
      Session 1 that was positively correlated with the magnitude of improvement in
      behavioral performance. Although we observed no significant changes in P1
      amplitude with VPL, both N1 amplitude and latency were significantly decreased in
      Session 2. Moreover, the difference in N1 latency between Session 1 and Session 2
      was negatively correlated with behavioral improvement. We also found a
      significant increase in P3 amplitude following training. Our results suggest that
      VPL of the TDT task may be due to plasticity in early visual cortical areas as
      well as changes in top-down attentional control and cognitive processing.

PMID- 29224983
TI  - Comparison of sensory structures on the antenna of different species of
      Philopotamidae (Insecta: Trichoptera).
AB  - Structure and distribution of sensilla were studied in sixteen species of the
      caddisfly family Philopotamidae. Their antennae bear numerous curved trichoid and
      pseudoplacoid sensilla and fewer coronal, styloconic and chaetoid sensilla on the
      flagellar segments. The most numerous pseudoplacoid sensilla have non-specific
      localization. The curved trichoid sensilla form clusters ventrally on each
      antennal segment. Sensilla belonging to coronal, styloconic and chaetoid types
      have specific positions. Long grooved trichoid sensilla are located
      nonspecifically in all the studied species. The average number of sensilla per
      segment decreases from the proximal to distal part of the flagellum. Scapus and
      pedicellum are devoid of most types of sensilla, however, they bear the Bohm
      bristles and long trichoid sensilla. A positive correlation between antenna
      dimensions and its cuticular structures is found.

PMID- 29224984
TI  - Variations in the opinion of breast surgeons and radiation oncologist regarding
      indications for radiation therapy after NSM: The need for prospective studies.

PMID- 29224985
TI  - Management and prognosis of locally recurrent rectal cancer - A national
      population-based study.
AB  - BACKGROUND: The rate of local recurrence of rectal cancer (LRRC) has decreased
      but the condition remains a therapeutic challenge. This study aimed to examine
      treatment and prognosis in patients with LRRC in Sweden. Special focus was
      directed towards potential differences between geographical regions and time
      periods. METHOD: All patients with LRRC as first event, following primary surgery
      for rectal cancer performed during the period 1995-2002, were included in this
      national population-based cohort-study. Data were collected from the Swedish
      Colorectal Cancer Registry and from medical records. The cohort was divided into
      three time periods, based on the date of diagnosis of the LRRC. RESULTS: In
      total, 426 patients fulfilled the inclusion criteria. Treatment with curative
      intent was performed in 149 patients (35%), including 121 patients who had a
      surgical resection of the LRRC. R0-resection was achieved in 64 patients (53%).
      Patients with a non-centrally located tumour were more likely to have positive
      resection margins (R1/R2) (OR 5.02, 95% CI:2.25-11.21). Five-year survival for
      patients resected with curative intent was 43% after R0-resection and 14% after
      R1-resection. There were no significant differences in treatment intention or R0
      resection rate between time periods or regions. The risk of any failure was
      significantly higher in R1-resected patients compared with R0-resected patients
      (HR 2.04, 95% CI:1.22-3.40). CONCLUSION: A complete resection of the LRRC is
      essential for potentially curative treatment. Time period and region had no
      influence on either margin status or prognosis.

PMID- 29224986
TI  - The effectiveness of a modified Metaizeau technique in fixation of adult radial
      neck fractures: a prospective study with a modification of the Broberg-Morrey
      classification.
AB  - BACKGROUND: The incidence of adult radial neck fractures is lower compared with
      its pediatric counterpart. The literature on adult radial neck fracture
      management is limited; also, there is a lack of a detailed fracture
      classification system. In our study, we are evaluating the modified Metaizeau
      technique for the treatment of adult radial neck fractures. We also describe a
      modification to the existing fracture classification proposed by Broberg and
      Morrey to make it more inclusive of different fracture patterns. MATERIALS AND
      METHODS: This is a prospective case series in which we included all the patients
      who presented to us with adult radial neck fractures. We used a modified
      Metaizeau technique to treat these fractures. Postoperatively, patients were
      followed up for a minimum duration of 1 year with a visual analog scale score,
      the Mayo Elbow Performance Score, the Oxford Elbow Score, the Disabilities of the
      Arm, Shoulder, and Hand score, and a subjective satisfaction questionnaire.
      RESULTS: We included a total of 7 patients who had completed follow-up of 1 year.
      Of the total 7 cases, 3 cases had an associated radial head fracture
      (undisplaced), and 1 had an associated radial shaft fracture (segmental pattern).
      Elastic nails were removed at 6 weeks, and all fractures united. The subjects
      returned to their preinjury activity levels by the end of 3 months and had
      excellent outcomes as measured by various outcome scores. CONCLUSION: The
      modified Metaizeau technique for closed reduction and internal fixation of adult
      radial neck fractures is effective and simple and has no complications compared
      with other treatment methods. However, further studies with larger sample sizes
      are needed to arrive at a more meaningful conclusion.

PMID- 29224987
TI  - Tobacco Smoke Exposure Association With Lipid Profiles and Adiposity Among U.S.
      Adolescents.
AB  - PURPOSE: We investigated the association between tobacco smoke exposure (TSE) as
      measured by serum cotinine and lipoprotein cholesterols and adiposity in
      adolescents. METHODS: We performed a secondary analysis of 1999-2012 National
      Health and Nutrition Examination Survey data including participants 12-19 years
      old. We examined TSE: unexposed (<.05 ng/mL), passively exposed (.05-2.99 ng/mL),
      and actively exposed (>=3 ng/mL); lipid profiles: total cholesterol, high-density
      lipoprotein cholesterol (HDL-C), non-HDL-C, low-density lipoprotein cholesterol
      (LDL-C), and triglycerides; and adiposity: body mass index z-score (BMIZ), waist
      circumference (WC), and waist-to-height ratio (WHtR). Covariates were age, sex,
      race/ethnicity, income, diet, and physical activity. Multiple regression models
      were used to assess the association between TSE and lipid profile variables
      separately, and then TSE and adiposity measures separately, adjusting for
      covariates. We performed logistic regression to examine the association of TSE
      with body mass index and WHtR classifications. RESULTS: Of the 11,550
      participants, 41.7% were unexposed to tobacco smoke, 40.5% were passively
      exposed, and 17.8% were actively exposed. Compared with unexposed, participants
      with active TSE had lower total cholesterol, lower HDL-C, and higher
      triglycerides; higher BMIZ, higher WC, and higher WHtR; participants with passive
      TSE had lower HDL-C, higher total cholesterol, and higher LDL-C; higher BMIZ,
      higher WC, and higher WHtR. Participants actively exposed were at increased odds
      of being obese or WHtR >=.65, and those passively exposed were at increased odds
      of being overweight, obese, or WHtR >=.65. CONCLUSIONS: Active TSE and passive
      TSE are differentially associated with factors within the lipid profile and
      adiposity, independent of covariates. TSE prevention efforts should start as
      early as childhood and continue throughout adolescence and adulthood.

PMID- 29224988
TI  - Linking HIV-Negative Youth to Prevention Services in 12 U.S. Cities: Barriers and
      Facilitators to Implementing the HIV Prevention Continuum.
AB  - PURPOSE: Linkage of HIV-negative youth to prevention services is increasingly
      important with the development of effective pre-exposure prophylaxis that
      complements behavioral and other prevention-focused interventions. However,
      effective infrastructure for delivery of prevention services does not exist,
      leaving many programs to address HIV prevention without data to guide program
      development/implementation. The objective of this study was to provide a
      qualitative description of barriers and facilitators of linkage to prevention
      services among high-risk, HIV-negative youth. DESIGN: Thematic analysis of
      structured interviews with staff implementing linkage to prevention services
      programs for youth aged 12-24 years. METHODS: Twelve adolescent medicine HIV
      primary care programs as part of larger testing research program focused on young
      sexual minority men of color. The study included staff implementing linkage to
      prevention services programs along with community-based HIV testing programs. The
      main outcomes of the study were key barriers/facilitators to linkage to
      prevention services. RESULTS: Eight themes summarized perspectives on linkage to
      prevention services: (1) relationships with community partners, (2) trust between
      providers and youth, (3) youth capacity to navigate prevention services, (4) pre
      exposure prophylaxis specific issues, (5) privacy issues, (6) gaps in health
      records preventing tailored services, (7) confidentiality of care for youth
      accessing services through parents'/caretakers' insurance, and (8) need for
      health-care institutions to keep pace with models that prioritize HIV prevention
      among at-risk youth. Themes are discussed in the context of factors that
      facilitated/challenged linkage to prevention services. CONCLUSIONS: Several
      evidence-based HIV prevention tools are available; infrastructures for
      coordinated service delivery to high-risk youth have not been developed.
      Implementation of such infrastructures requires attention to community-, provider
      , and youth-related issues.

PMID- 29224990
TI  - The Shift to Same-Day Outpatient Joint Arthroplasty: A Systematic Review.
AB  - BACKGROUND: Hip and knee arthroplasties length of stay continues to shorten after
      advances in perioperative and intraoperative management, as well as financial
      incentives. Some authors have demonstrated good results with outpatient
      arthroplasty, but safety and general feasibility of such procedures remain
      unclear. Our hypothesis is that outpatient arthroplasty would demonstrate higher
      readmission and complication rates than inpatient arthroplasty. METHODS: We
      performed a systematic review of all publications on outpatient arthroplasty
      between January 1, 2000 and June 1, 2016. Included publications had to
      demonstrate a specific outpatient protocol and have reported perioperative
      complications and unplanned readmissions. Patient demographics, surgical
      variables, and protocol details were recorded in addition to complications,
      readmission, and reoperation. RESULTS: Ten manuscripts accounting for 1009
      patients demonstrated that 955 (94.7%) were discharged the same day as planned,
      with the majority of failures to discharge being secondary to pain, hypotension,
      and nausea. There were no deaths and only 1 major complication. Only 20 patients
      (1.98%) required reoperation and 20 (1.98%) had readmission or visited the
      emergency room within 90 days of their operation. In the 2 series recording
      patient outcomes, 80% and 96% of patients reported that they would choose to
      undergo outpatient arthroplasty again. CONCLUSION: For carefully selected
      patients with experienced surgeons in major centers, outpatient arthroplasty may
      be a safe and effective procedure. Although our data is promising, further study
      is required to better elucidate the differences between inpatient and outpatient
      arthroplasty outcomes.

PMID- 29224989
TI  - Synovial Calprotectin: An Inexpensive Biomarker to Exclude a Chronic Prosthetic
      Joint Infection.
AB  - BACKGROUND: To diagnose or exclude a chronic prosthetic joint infection (PJI) can
      be a clinical challenge. Therefore, sensitive and specific biomarkers are needed
      in the diagnostic work-up. Calprotectin is a protein with antimicrobial
      properties and is released by activated neutrophils, making it a specific marker
      for infection. Because of its low costs and ability to obtain a quantitative
      value as a point of care test, it is an attractive marker to use in clinical
      practice. In addition, the test is already used in routine care in most hospitals
      for other indications and therefore easy to implement. METHODS: Between June 2015
      and June 2017 we collected synovial fluid of all consecutive patients who
      underwent revision surgery of a prosthetic joint because of chronic pain with or
      without prosthetic loosening. Synovial calprotectin was measured using a lateral
      flow immunoassay. A PJI was defined by the diagnostic criteria described by the
      Musculoskeletal Infection Society. RESULTS: Fifty-two patients with chronic pain
      were included. A PJI was diagnosed in 15 of 52 (29%) patients. The median
      calprotectin in the PJI group was 859 mg/L (interquartile range 86-1707) vs 7
      mg/L (interquartile range 3-25) in the control group (P < .001). With a cut-off
      value of 50 mg/L, synovial calprotectin showed a sensitivity, specificity,
      positive predictive value, and negative predictive value of 86.7%, 91.7%, 81.3%,
      and 94.4%, respectively. CONCLUSION: Synovial calprotectin is a useful and cheap
      biomarker to use in the diagnostic work-up of patients with chronic pain,
      especially to exclude a PJI prior to revision surgery.

PMID- 29224991
TI  - Femoral Component Axial Rotation in the Gap-Balancing Approach to Total Knee
      Arthroplasty: Measurement by Computed Tomography.
AB  - BACKGROUND: Rotational malalignment of total knee arthroplasty (TKA) is a
      potential cause for revision surgery; therefore, it is important to have valid
      criteria for evaluation of normal component rotational alignment. Because
      computed tomography (CT) is considered the most accurate method to assess the
      rotational alignment of prosthetic components, the objectives in this study were
      define the femoral component (FC) rotation by measuring the posterior condylar
      angle (PCA) and the condylar twist angle (CTA) in a patient population that
      underwent gap-balancing TKA; determine the reliability of the FC rotation by
      using these measurements; evaluate the inter-relationship between the PCA and
      CTA; and finally evaluate the frequency and agreement in identification of the
      medial epicondyle sulcus (MES). METHODS AND RESULTS: In this retrospective study,
      2 radiologists examined 50 CT scans. Mean PCA values of -2.26 degrees  and -2.56
      degrees  (internal rotation) and CTA values of -5.54 degrees  and -6.28 degrees 
      (internal rotation) were attained by 2 observers with a higher interobserver
      concordance for the PCA. Both measurements were considered to be reliable. There
      was moderate interobserver agreement for MES identification, with the MES present
      in 64% and 78% of patients, as identified by 2 observers. CONCLUSION: Mean FC
      rotation values as evaluated by PCA were -2.26 degrees  and -2.56 degrees  and as
      evaluated by CTA were -5.54 degrees  and -6.28 degrees . PCA and CTA measurement
      by CT is reliable; however, the use of PCA is preferable because of the higher
      observer concordance. PCA can be inferred by subtracting 3 degrees  or 4 degrees 
      from the CTA. MES was identified in 64% and 78% of patients, with only moderate
      interobserver agreement.

PMID- 29224992
TI  - Experience Influences the Agreement and Reliability of Tibial Component
      Positioning in Total Knee Arthroplasty.
AB  - BACKGROUND: Poor rotation of the tibial component is associated with unfavorable
      total knee arthroplasty outcomes. Some surgeons utilize the tibial tubercle (TT
      method), while others utilize the femoral cam (Box method) as a rotational
      landmark during total knee arthroplasty. Our purpose is to determine the
      reproducibility of 2 methods for establishing intra-operative tibial component
      rotation, while also comparing the effect of level of training. METHODS: Twelve
      surgeons positioned and sized a symmetric tibial component on 7 cadaver knees.
      Surgeons were allowed to utilize their preferred method for establishing tibial
      component rotation. Seven surgeons selected the TT method, 4 utilized the Box
      method, and 1 used both methods depending on the specimen. Repeat measurements
      were completed by each surgeon after a rest period. The differences between
      tibial tray positions were assessed using computer-assisted optoelectronic
      measurements. Intra-class correlation coefficients were calculated to determine
      inter-observer agreement (IOA) and intra-rater reliability (IRR). RESULTS:
      Overall, both the Box method and the TT method demonstrated high IRR for tibial
      component rotation. Experienced surgeons were more consistent at establishing
      component rotation regardless of technique. Trainees were more consistent when
      utilizing the Box method (IRR 0.96, IOA 0.94) than the TT method (IRR 0.71, IOA
      0.72). CONCLUSION: Surgeon experience influences the agreement and reliability of
      tibial component position. For less experienced surgeons, the Box method was more
      effective than the TT method for consistently reproducing tibial component
      rotation.

PMID- 29224993
TI  - Embolization of the Geniculate Arteries Is an Effective Treatment of Recurrent
      Hemarthrosis Following Total Knee Arthroplasty That Can Be Safely Repeated.
AB  - BACKGROUND: Recurrent hemarthrosis is a late complication in up to 1.6% of
      patients following total knee arthroplasty (TKA). In the absence of intrinsic
      coagulopathy, one etiology is bleeding of hypertrophic vascular synovium. The aim
      of this study is to evaluate the clinical outcome of patients referred to our
      center for angiographic embolization of geniculate arteries for recurrent
      hemarthrosis following TKA. METHODS: We retrospectively studied a cohort of
      patients who were referred for geniculate artery embolization following TKA
      between August 2011 and September 2016. RESULTS: A total of 24 embolization
      procedures were performed on 14 patients. Seven (50%) of these 14 patients
      underwent one embolization procedure. Due to symptom recurrence, 4 patients
      underwent a repeated procedure and 3 patients a third procedure. All embolization
      procedures were technically successful at the time of the procedure. Two patients
      reported an inguinal hematoma that healed without further treatment. At follow-up
      of mean 26.8 months, clinical success was achieved in 12 of the 14 patients
      (86%). CONCLUSION: Embolization of the geniculate arteries in our study was a
      safe and effective treatment of recurrent spontaneous hemarthrosis following TKA.
      Although we have performed a substantial number of reinterventions, results of
      this study show that this procedure can be safely repeated without adverse
      events. Our results indicate that embolization could possibly be the treatment of
      choice when conservative measures fail and can be repeated in the event of
      recurrent or persistent symptoms.

PMID- 29224995
TI  - Evaluation of alkylating pyrrole-imidazole polyamide conjugates by a novel method
      for high-throughput sequencer.
AB  - N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove
      binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are
      attractive candidates as anticancer drugs acting through DNA damage and its
      subsequent inhibition of cell proliferation. One example is a chlorambucil-PI
      polyamide conjugate targeting the runt-related transcription factor (RUNX)
      family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and
      recently the chlorambucil-PI polyamide conjugate was demonstrated to have
      anticancer effects. Herein, we apply another DNA-alkylating agent, seco-CBI, to
      target the consensus sequence of the RUNX family. Two types of CBI conjugates
      were prepared and their binding properties were characterized by Bind-n-Seq
      analysis using a high-throughput sequencer. The sequencing data were analyzed by
      two methods, MERMADE and our new MR (motif identification with a reference
      sequence), and the resultant binding motif logos were as predicted from the
      pairing rules proposed by Dervan et al. This is the first report to employ the MR
      method on alkylating PI polyamide conjugates. Moreover, cytotoxicity of
      conjugates 3 and 4 against a human non-small cell lung cancer, A549, were
      examined to show promising IC50s of 120 nm and 63 nm, respectively. These
      findings suggest seco-CBI-PI polyamide conjugates are candidates for oncological
      therapy.

PMID- 29224994
TI  - Antitussive and expectorant activities of licorice and its major compounds.
AB  - Licorice has been used as an antitussive and expectorant herbal medicine for a
      long history. This work evaluated the activities of 14 major compounds and crude
      extracts of licorice, using the classical ammonia-induced cough model and phenol
      red secretion model in mice. Liquiritin apioside (1), liquiritin (2), and
      liquiritigenin (3) at 50 mg/kg (i.g.) could significantly decrease cough
      frequency by 30-78% (p < .01). The antitussive effects could be partially
      antagonized by the pretreatment of methysergide or glibenclamide, but not
      naloxone. Moreover, compounds 1-3 showed potent expectorant activities after 3
      days treatment (p < .05). The water and ethanol extracts of licorice, which
      contain abundant 1 and 2, could decrease cough frequency at 200 mg/kg by 25-59%
      (p < .05), and enhance the phenol red secretion (p < .05), while the ethyl
      acetate extract showed little effect. These results indicate liquiritin apioside
      and liquiritin are the major antitussive and expectorant compounds of licorice.
      Their antitussive effects depend on both peripheral and central mechanisms.

PMID- 29224996
TI  - Cost-effectiveness of the non-laboratory based Framingham algorithm in primary
      prevention of cardiovascular disease: A simulated analysis of a cohort of African
      American adults.
AB  - The non-lab Framingham algorithm, which substitute body mass index for lipids in
      the laboratory based (lab-based) Framingham algorithm, has been validated among
      African Americans (AAs). However, its cost-effectiveness and economic tradeoffs
      have not been evaluated. This study examines the incremental cost-effectiveness
      ratio (ICER) of two cardiovascular disease (CVD) prevention programs guided by
      the non-lab versus lab-based Framingham algorithm. We simulated the World Health
      Organization CVD prevention guidelines on a cohort of 2690 AA participants in the
      Atherosclerosis Risk in Communities (ARIC) cohort. Costs were estimated using
      Medicare fee schedules (diagnostic tests, drugs & visits), Bureau of Labor
      Statistics (RN wages), and estimates for managing incident CVD events. Outcomes
      were assumed to be true positive cases detected at a data driven treatment
      threshold. Both algorithms had the best balance of sensitivity/specificity at the
      moderate risk threshold (>10% risk). Over 12years, 82% and 77% of 401 incident
      CVD events were accurately predicted via the non-lab and lab-based Framingham
      algorithms, respectively. There were 20 fewer false negative cases in the non-lab
      approach translating into over $900,000 in savings over 12years. The ICER was 
      $57,153 for every extra CVD event prevented when using the non-lab algorithm. The
      approach guided by the non-lab Framingham strategy dominated the lab-based
      approach with respect to both costs and predictive ability. Consequently, the non
      lab Framingham algorithm could potentially provide a highly effective screening
      tool at lower cost to address the high burden of CVD especially among AA and in
      resource-constrained settings where lab tests are unavailable.

PMID- 29224997
TI  - In vitro assessment of the anti-biofilm activity of ethanol alone and in
      combination with enoxaparin 60IU.
AB  - INTRODUCTION: Catheter-related bloodstream infection (C-RBSI) can sometimes be
      managed without catheter removal by combining systemic therapy with catheter lock
      therapy. Most antiseptic lock solutions are made up of ethanol combined with an
      anticoagulant. However, data regarding the anti-biofilm activity of ethanol
      combined with enoxaparin are scarce. We aimed to assess the efficacy of ethanol
      at different concentrations combined with enoxaparin 60IU as a lock solution for
      eradication of the biofilm of different microorganisms. METHODS: Using a static
      96-well plate in vitro model, we tested 30%, 35%, and 40% ethanol alone and
      combined with 60IU of enoxaparin against 24-h-old biofilm from the following
      microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus
      faecalis, Escherichia coli, and Candida albicans. Time of exposure was assessed
      during a 2-h and 24-h regimen. We analysed the percentage reduction in metabolic
      activity using the XTT assay. We considered therapy to be successful when
      metabolic activity was reduced by >90%. RESULTS: In the 2-h regimen, the therapy
      was successful against all microorganisms at 35% and 40% ethanol without
      enoxaparin (p<0.001). In the 24-h regimen, the therapy was successful against all
      microorganisms at all ethanol solutions without enoxaparin (p<0.001). When
      ethanol was combined with enoxaparin, the therapy was only successful in the 24-h
      regimen in biofilms of S. epidermidis, C. albicans and E. coli at all
      concentrations of ethanol assessed. CONCLUSIONS: Our in vitro model demonstrated
      that when ethanol is combined with enoxaparin in a lock solution, it negatively
      affects ethanol anti-biofilm activity after both short and long exposures.

PMID- 29224998
TI  - Neonatal epididymo-orchitis with pyocele caused by Escherichia coli: Successful
      treatment with antimicrobial therapy alone.

PMID- 29224999
TI  - [Anemia of chronic kidney disease: Protocol of study, management and referral to
      Nephrology].
AB  - The objective of this protocol is to know which test are needed to study an
      anaemia in a patient with chronic kidney disease, the differential diagnosis of
      renal anaemia, to know and correct other deficiency anaemias, and the criteria
      for referral to Nephrology or other specialties of the anaemic patient with
      chronic kidney disease.

PMID- 29225000
TI  - [Validity of the abdominal ecography in primary care for detection of aorta
      abdominal aneurism in male between 65 and 75 years].
AB  - OBJECTIVE: To determine the usefulness of ultrasound examination in Primary Care
      (PC) for the detection of abdominal aortic aneurysm (AAA) in male patients from
      65-75 years old, as well as the consistency between observers on the diagnosis
      between general practitioners and the reference specialty in this area, Vascular
      Surgery. To estimate the prevalence of AAA in that population and its association
      with risk factors. DESIGN: Cross-sectional descriptive study. LOCATION:
      Healthcare Centres of Coto and Calzada II (Gijon, Spain). PARTICIPANTS: Males
      born between 1 January 1939 and 31 December 1950. INTERVENTIONS: From the 2,511
      males found, 407 were selected using stratified random sampling. Aortic diameter
      was measured, with those >=3cm and 20% from the <3cm being referred for a second
      measurement by a vascular surgeon. VARIABLES: Dependent: presence/absence of
      aneurism. Independent: age, abdominal perimeter, smoking, arterial hypertension,
      diabetes, dyslipidaemia, familial cases of AAA, cerebrovascular accident, and
      coronary disease. The analysis was performed using Bayesian inference with models
      for proportions and a multivariate logistic regression. RESULTS: From 304
      ultrasound scans performed, 13 were referred with suspicion of AAA, and 63 with
      were within normal. The sensitivity was 93.3% and specificity 98.5% with a 95%
      credibility interval (CredI) of 75.4-99.9%, and 94.3-100%, respectively. The
      prevalence was 4.6% (95% CredI: 2.5-7.2%, and the intraclass correlation
      coefficient between PC and Vascular Surgery was 0.88 (95% CredI: 0.79-0.94). Age,
      smoking, dyslipidaemia, and diabetes tended to increase the odds of prevalence of
      AAA. CONCLUSION: The ultrasound performed by GPs for the detection of AAA had
      high diagnostic validity. Further studies on the effectiveness should be
      conducted in order to assess the appropriateness of introducing a system of early
      detection of AAA in the risk population.

PMID- 29225001
TI  - Dorsal hippocampal cannabinergic and GABAergic systems modulate memory
      consolidation in passive avoidance task.
AB  - In the present research, we examined the possible interaction between the
      hippocampal CB2 and GABAA receptors on modulation of memory consolidation. In
      this research, step-down passive a . voidance task was used to evaluate memory
      consolidation in adult male NMRI mice. The results showed that post-training
      intra-CA1 administration of muscimol (0.05 and 0.1 MUg/mouse) impaired memory
      consolidation as evidenced by a decrease in step-down latency on the test day,
      which was suggestive of drug-produced amnesia. However co-administration of
      different doses of muscimol (0.01, 0.05 and 0.1 MUg/mouse) along with a not
      effect dose of AM630 (1 MUg/mouse) or GP1a (1 MUg/mouse) had no significant
      effect on impairment of memory consolidation induced by muscimol. Although post
      training intra-CA1 administration of the cannabinoid CB2 receptor antagonist,
      AM630 (1, 10 and 100 MUg/mouse) alone had no effect, its co-administration with
      an effective dose of muscimol (0.05 MUg/mouse) impaired memory consolidation.
      Furthermore, post-training intra-CA1 microinjection of cannabinoid CB2 receptor
      agonist, GP1a (100 MUg/mouse) impaired memory consolidation. Interestingly, post
      training intra-CA1 co-injection of different doses of GP1a (1, 10 and 100
      MUg/mouse) along with an effect dose of muscimol (0.05 MUg/mouse) significantly
      intensified impairment of memory consolidation induced by GP1a (10 MUg/mouse).
      Moreover, all above doses of drugs did not significantly change locomotor
      activity. These findings suggest possible interaction between the CA1 cannabinoid
      CB2 and GABAA mechanisms on modulation of memory consolidation in mice.

PMID- 29225002
TI  - Documentation of 'Plant Drugs' dispensed via local weekly shanties of Madurai
      City, India.
AB  - BACKGROUND: The Valaiyar (Moopanar) communities of Tamil Nadu are traditionally
      known for catching rats and snakes from the agricultural fields. Prior to
      independence, some of these families have faced socio-economic changes and chosen
      to become herbalists in Madurai city. They are mainly engaged in collecting and
      dispensing fresh and dried plant drugs in its 'natural form' at Tilagar tidal
      market of Madurai city. Their business is unique, because customers receive
      'prescriptions' and 'plant drugs', unlike the conventional dispensaries. Their
      world view is: 'to cure the ailing in natural way'. OBJECTIVES: To document plant
      drugs collected and dispensed by some of the families belonging to Valaiyar
      (Moopanar) community in the Tilagar tidal market. MATERIALS AND METHODS:
      Ethnobotanical tools were employed to document various aspects of the practices
      including resource and knowledge base, medicinal uses, dosage, collection of
      herbarium and raw drug specimens. Integrative approach was adapted to document
      the trade dynamics. RESULTS: During the study, 133 medicinal plant species
      belonging to 50 families were documented. 71% of species were sourced from wild
      and non-forest areas. 272 simple and compound remedies were recorded. CONCLUSION:
      Local markets/shanties like these are 'Traditional Medicine (TM) health care
      services at door step'. They cater to local health care needs along with
      conventional system in a synergistic manner and provide adaptable, local
      solutions using local resources.

PMID- 29225003
TI  - Improving patient safety during procedural sedation via respiratory volume
      monitoring: A randomized controlled trial.
AB  - STUDY OBJECTIVE: Assess the utility of a respiratory volume monitor (RVM) to
      reduce the incidence of low minute ventilation events in procedural sedation.
      DESIGN: Randomized control trial SETTING: Endoscopy suite PATIENTS: Seventy-three
      total patients (ASA Physical Status 1-3) undergoing upper endoscopies were
      analyzed. INTERVENTION: Patients were randomized into two groups using a computer
      generated randomization table: Control (n=41): anesthesia provider was unable to
      see the screen of the RVM; RVM (n=32): anesthesia provider had access to RVM data
      to assist with management of the case. MEASUREMENTS: Minute ventilation (MV),
      tidal volume, and respiratory rate were continuously recorded by the RVM. MV is
      presented as percent of Baseline MV (MVBaseline), defined during a 30s period of
      quiet breathing prior to sedation. We defined Low MV as MV<40% MVBaseline, and
      calculated the percentage of procedure spent with Low MV. Patients in the RVM
      group were stratified based on whether the anesthesiologist rated the RVM as "not
      useful", "somewhat useful", or "very useful" during the case. MAIN RESULTS:
      Control patients experienced twice as much Low MV compared to RVM patients
      (15.3+/-2.8% vs. 7.1+/-1.4%, P=0.020). The "not useful" (13.7+/-3.8%) group
      showed no improvement over the Control group (p=0.81). However, both the "very
      useful" (4.7+/-1.4%) and "somewhat useful" (4.9+/-1.7%) groups showed significant
      improvement over the "not useful" group (p<0.05). CONCLUSIONS: Patients in the
      Control group spent more than double the amount of time with Low MV compared to
      the RVM group. This difference became more pronounced when the anesthesiologist
      found the RVM useful for managing care, lending credibility to the usage of
      minute ventilation monitoring in procedural sedation.

PMID- 29225004
TI  - Suppressor of cytokine signaling 6 can enhance epidermal growth factor receptor
      signaling pathway in Bombyx mori (Dazao).
AB  - The SOCS (Suppressor of cytokine signaling) family members are a potential
      negative regulator of cytokine signaling pathway and play a key role to maintain
      immunological functions in animals. SOCS-6 is an important member of the SOCS
      family, however the functions of this gene have rarely been explored among
      eukaryotes. Herein, we cloned and expressed SOCS-6 gene from Bombyx mori (Dazao)
      (BmSOCS-6), and anti-rabbit antibodies were prepared using purified recombinant
      BmSOCS-6 protein. Under normal physiological conditions, the BmSOCS-6 expression
      was observed at varied levels in six tissues, with most greatly expressed in fat
      body and hemocytes. After immune challenge with viral, fungal and bacterial
      pathogens, the BmSOCS-6 showed distinctly varied expression patterns in tissue,
      time and microbe dependent manner. By contrast, recombinant BmSOCS-6 protein
      strongly enhanced the expression of epidermal growth factor receptor (EGFR)
      pathway related genes, while the depletion of BmSOCS-6 by double stranded RNA
      suppressed their production. Altogether we concluded that BmSOCS-6 may improve
      the efficiency of EGFR signaling pathway in B. mori (Dazao).

PMID- 29225005
TI  - Eicosanoid-mediated immunity in insects.
AB  - Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated
      fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating
      various physiological processes, including immune responses, in insects. Upon
      microbial pathogen infection, non-self recognition signals are propagated to
      nearly immune effectors such as hemocytes and fat body using various immune
      mediators, in which eicosanoid signals act as the ultimate downstream mediator.
      The chemical diversity of eicosanoids may operate to mediate various immune
      responses. Some entomopathogenic bacteria suppress eicosanoid biosynthesis, which
      inhibits host insect immunity and promotes their pathogenicity. This review
      introduces immune responses mediated by various eicosanoids. Then it explains the
      cross-talks of eicosanoids with other immune mediators including cytokines,
      biogenic monoamines, and nitric oxide to clarify the complexity of insect immune
      mediation. Finally, we highlight the biological significance of eicosanoids by
      demonstrating bacterial pathogenicity inhibiting a key enzyme - phospholipase A2 
      in eicosanoid biosynthesis using their secondary metabolites to defend host
      insect immune attack.

PMID- 29225007
TI  - High-sensitivity quantitative analysis reveals the non-linear relationship
      between the dose and deposition of diphenylarsinic acid in the rat central
      nervous system following its subchronic exposure.
AB  - In the year 2003, the residents of Kamisu, Japan, were exposed to pentavalent
      organic arsenic diphenylarsinic acid (DPAA[V]) via their normal drinking water.
      Following the exposure, they developed cerebellar and brainstem symptoms.
      Although the relatively high dose of DPAA(V) is assumed to have caused their
      symptoms, the relationship between the exposed dose of DPAA(V) and the level of
      their deposition in the central nervous system (CNS) remains unclear. Using
      liquid chromatography-tandem mass spectrometry, we examined the deposition of
      DPAA(V) and its pentavalent metabolites in the CNS tissues of Crl:CD(SD) rats
      following the administration of DPAA(V) for 28days. We found that the
      concentrations of DPAA(V) in the CNS were very high, given a dose of
      5.0mg/kg/day. However, very low concentrations of DPAA(V) were detected at a dose
      of 0.3 or 1.2mg/kg/day, suggesting the absence of a linear dose-response
      relationship between the dose and deposition of DPAA(V). We also found that this
      non-linear relationship was commonly observed in various non-CNS tissues,
      including the excretory system. Our study showed for the first time the exact
      relationship between the dose and tissue deposition of the organic arsenic
      following its subchronic administration.

PMID- 29225006
TI  - Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish
      embryos.
AB  - Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+-permeable N
      methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic
      and has been implicated in developmental neurotoxicity. Ketamine has also been
      shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl
      l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity
      in zebrafish embryos. Based on our finding that ALCAR's protective effect was
      blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated
      the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in
      zebrafish embryos. The results demonstrated that ketamine reduced ATP levels in
      the embryos but not in the presence of ALCAR. Ketamine reduced total
      mitochondrial protein levels and mitochondrial potential, which were prevented
      with ALCAR co-treatment. To determine the cause of ketamine-induced ATP
      deficiency, we explored the status of ATP synthase. The results showed that a
      subunit of ATP synthase, atp5alpha1, was transcriptionally down-regulated by
      ketamine, but not in the presence of ALCAR, although ketamine caused a
      significant upregulation in another ATP synthase subunit, atp5beta and total ATP
      synthase protein levels. Most of the ATP generated by heart mitochondria are
      utilized for its contraction and relaxation. Ketamine-treated embryos showed
      abnormal heart structure, which was abolished with ALCAR co-treatment. This study
      offers evidence for a potential mechanism by which ketamine could cause ATP
      deficiency mediated by mitochondrial dysfunction.

PMID- 29225008
TI  - Soft palate functional reconstruction with buccinator myomucosal island flaps.
AB  - Oropharyngeal reconstruction after ablative surgery is a challenge. The results
      of a retrospective study of 17 patients who underwent total or sub-total soft
      palate reconstruction with a buccinator myomucosal island flap, between 2008 and
      2016, are reported herein. An analysis of flap type and size, harvesting time,
      and postoperative complications was performed. Patients underwent standardized
      tests to assess the recovery of sensitivity, deglutition, quality of life (QoL),
      and donor site morbidity, at >6 months after surgery or the end of adjuvant
      therapy, if performed. All flaps were transposed successfully. Only minor donor
      and recipient site complications occurred. The sensitivity assessment showed that
      touch, two-point discrimination, and pain sensations were recovered in all
      patients. Significant differences between the flap and native mucosa were
      reported for tactile (P=0.004), pain (P=0.001), and two-point discrimination
      (P=0.001) thresholds. The average deglutition score reported was 6.1/7, with only
      minimal complaints regarding deglutition. The QoL assessment showed high physical
      (24.6/28), social (25/28), emotional (19.1/24), and functional (24.6/28) scores.
      No major donor site complications were noted in any patient; the average donor
      site morbidity score was 8.1/9. Buccinator myomucosal island flaps represent a
      valuable functional oropharyngeal option for reconstruction, requiring a short
      operating time and presenting a low donor site morbidity rate.

PMID- 29225009
TI  - Anatomic implications of lesser trochanterplasty.
AB  - OBJECTIVE: The aim of this study was to measure the area of iliopsoas tendon
      attachment and the distance of sciatic nerve, medial circumflex femoral artery
      (MCFA) and quadratus muscle to lesser trochanter tip, before and after 5, 10, 15
      mm depth excision of lesser trochanter. METHODS: A total 15 hips of 8 adult male
      cadavers were evaluated. Distances between lesser trochanter tip, sciatic nerve,
      the lower edge of quadratus muscle and MCFA; length and width of quadratus muscle
      insertion; area of iliopsoas muscle and quadratus muscle insertion was measured
      before and after sequential 5,10 and 15 mm depth trochanterplasties using 5 mm
      wide burr parallel to the posterior cortex. RESULTS: Each incremental 5 mm depth
      bone removal led to significant decrease of tendon area (p=0.001) at each stage.
      Mean decreases of iliopsoas tendon attachment area with incremental 5 mm burring
      were 22%+/-10 with 5 mm, 50%+/-13 with 10 mm, and 76% +/-13 with 15 mm of
      burring. CONCLUSION: Up to 15 mm lesser trochanter removal did not result in
      complete detachment of the iliopsoas tendon. Lesser trochanter tip was detected
      at least 20 mm away from important anatomic structures including quadratus
      tendon, sciatic nerve, and the medial circumflex femoral artery.

PMID- 29225010
TI  - Initiation and outcomes with Class Ic antiarrhythmic drug therapy.
AB  - BACKGROUND: Expert opinion recommends performing exercise testing with initiation
      of Class Ic antiarrhythmic medication. OBJECTIVE: To evaluate the rate and reason
      for discontinuation of Ic agent within the first year of follow up, with
      particular attention to rate of proarrhythmia and the value of routine treadmill
      testing. METHODS: This is a single center retrospective cohort study including
      consecutive patients with atrial arrhythmias who were initiated on a Class Ic
      agent from 2011 to 2016. Data was collated from chart review and pharmacy
      database. RESULTS: The study population included 300 patients (55% male, mean age
      61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and
      propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on
      telemetry and the staff electrophysiologists directed dosing. There was one
      proarrhythmic event during initiation (0.3%). The primary reason for not being
      discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia
      (n = 1) with treadmill testing (5.3%). Exercise testing was the single
      significant variable to affect the decision to discontinue Ic drug, p < 0.0001
      (95% CI: 1.89-6.08%). During follow up, the primary reason for discontinuation of
      Ic agent was lack of efficacy, 32%. CONCLUSIONS: With proper screening,
      initiation of Class Ic agent is associated with very low rate of proarrhythmia.
      Treadmill testing is of incremental value and should be completed in all patients
      after loading Class Ic antiarrhythmic.

PMID- 29225011
TI  - Effect of platelet-lymphocyte ratio and lactate levels obtained on mortality with
      sepsis and septic shock.
AB  - BACKGROUND: Sepsis is a potentially fatal condition with high treatment costs,
      and is especially common among the elderly population. The emergency management
      of septic patients has gained importance. OBJECTIVE: Herein, we investigated the
      effect of admission lactate levels and the platelet-lymphocyte ratio (PLR) on the
      30-day mortality among patients older than 65years who were diagnosed with sepsis
      and septic shock according to the qSOFA criteria at our hospital's emergency
      department. METHODS: This observational study was conducted retrospectively. We
      obtained information regarding patients' demographic characteristics, comorbid
      conditions, hemodynamic parameters at admission, initial treatment needs at the
      emergency department. RESULTS: 131 patients received a diagnosis of sepsis and
      septic shock at our emergency department in two years. Among these, 45% (n=59) of
      the patients died within 30days of admission. Forty (30.5%) patients required
      mechanical ventilation. There was a significant difference between the survival
      and non-survival groups with regard to systolic and diastolic blood pressures
      (p=0.013 and 0.045, respectively). There were significant differences between the
      two groups with respect to the Glasgow Coma Scale score (p<0.001) and BUN levels
      (p<0.001). The mortality status according to qSOFA scores was revealed a
      significant difference between the two groups (p<0.001). CONCLUSION: Our results
      showed that the patients who died within 30days of admission and those who did
      not had comparable PLR and lactate levels (p=0.821 and 0.120, respectively). We
      opine that serial lactate measurements would be more useful than a single
      admission lactate measurement for the prediction of mortality.

PMID- 29225012
TI  - Comparison of 3 techniques in percutaneous tracheostomy: Traditional landmark
      technique; ultrasonography-guided long-axis approach; and short-axis approach -
      Randomised controlled study.
AB  - INTRODUCTION: The aim of this study is to compare the reliabilities of the
      traditional landmark method, ultrasonography-guided long-axis in-plane
      application, and ultrasonography-guided short-axis out-of-plane application in
      percutaneous dilatational tracheostomy. PATIENTS AND METHODS: A total of 60
      patients were divided in 3 random groups undergoing percutaneous tracheostomy by
      using landmark method, ultrasonography-guided out-of-plane method, and
      ultrasonography-guided in-plane method. While demographic data of the patients
      were recorded before the procedure, number of punctures, success rate at the
      first entry, rate of successful tracheostomy tube placement, total tracheostomy
      time, and complications were recorded during and after the procedure. RESULTS AND
      DISCUSSION: It was found that 23 women and 37 men were included in the study, the
      average age of the cases was 68.0+/-15.5; mean body mass index was 27.9+/-4.3;
      mean APACHE II scores were 27.4+/-4.6 and there was no significant difference
      between the groups in terms of demographic data. The ultrasonography-guided out
      of-plane application had significantly lower number of punctures, higher first
      entry success, and fewer complications compared to the other groups.
      Independently from the groups, first entry success was significantly low in
      advanced age and number of punctures significantly increased the complication
      rate. CONCLUSION: In this randomised controlled study, it was found that
      ultrasonography-guided out-of-plane application had lower number of punctures,
      higher first entry success rate, and less complications. It was observed that
      advanced age negatively affected the first entry success and as number of
      punctures increased, the complication rate increased. ClinicalTrials.gov ID:
      NCT02855749.

PMID- 29225013
TI  - Succinate dehydrogenase: Prospect for neurodegenerative diseases.
AB  - Onset of Alzheimer's, Parkinson's and Huntington's diseases as neurodegenerative
      disorders is increased by age. Alleviation of clinical symptoms and protection of
      neurons against degeneration are the main aspects of researches to establish new
      therapeutic strategies. Many studies have shown that mitochondria play crucial
      roles in high energy demand tissues like brain. Impairments in mitochondrial
      activity and physiology can makes neurons vulnerable to stress and degeneration.
      Succinate dehydrogenase (SDH) connects tricarboxylic cycle to the electron
      transport chain. Therefore, dysfunction of the SDH could impair mitochondrial
      activity, ATP generation and energy hemostasis in the cell. Exceed lipid
      synthesis, induction of the excitotoxicity in neurodegenerative disorders could
      be controlled by SDH through direct and indirect mechanism. In addition, mutation
      in SDH correlates with the onset of neurodegenerative disorders. Therefore, SDH
      could behave as a key regulator in neuroprotection. This review will present
      recent findings which are about SDH activity and related pathways which could
      play important roles in neuronal survival. Additionally, we will discuss about
      all possibilities which candidate SDH as a neuroprotective agent.

PMID- 29225014
TI  - Leber's hereditary optic neuropathy caused by a mutation in mitochondrial tRNAThr
      in eight Chinese pedigrees.
AB  - PURPOSE: The purpose of this study was to investigate the pathophysiology
      underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial
      tRNA mutation. METHODS: Severn hundred ninety-seven Han Chinese subjects
      underwent clinical and genetic evaluation and analysis of mitochondrial DNA
      (mtDNA). The cybrid cell lines were constructed by transferring mitochondria from
      lymphoblastoid cell lines derived from a Chinese family into mtDNA-less (rhoo)
      cells. These cell lines were assayed by tRNA Northern blot and Western blot
      analyses, respiratory enzymatic activities, the rate of ATP production and the
      generation of reactive oxygen species. RESULTS: The tRNAThr 15927G>A mutation was
      identified in eight probands with suggestively maternal inheritance among 352 Han
      Chinese probands lacking these known LHON-associated mtDNA mutations. The
      m.15927G>A mutation affected a highly conserved guanine at position 42 at the
      anticodon-stem of tRNAThr, destabilizing the conservative base pairing (28C-42G).
      We therefore hypothesized that the m.15927G>A mutation, and altered the structure
      and function of tRNAThr. Northern blot analysis revealed 60% decrease in the
      steady-state level of tRNAThr in the mutant cell lines. Western blot analysis
      showed the variable reductions of 4 mtDNA encoding proteins, especially for
      marked decrease of ND1 and CYTB observed in mutant cell lines. Furthermore, we
      demonstrated that the m.15927G>A mutation decreased the activities of
      mitochondrial complexes I and III, markedly diminished mitochondrial ATP levels,
      and increased the production of reactive oxygen species in the mutant cells.
      CONCLUSIONS: Our data demonstrated the first mitochondrial tRNA mutation leading
      to LHON. Our findings may provide new insights into the understanding of
      pathophysiology of LHON.

PMID- 29225015
TI  - Symptomatic Focal Knee Chondral Injuries in National Football League Combine
      Players Are Associated With Poorer Performance and Less Volume of Play.
AB  - PURPOSE: To (1) describe the magnetic resonance imaging (MRI) characteristics of
      knee chondral injuries identified at the National Football League (NFL) Combine
      and (2) assess in-game performance of prospective NFL players with previously
      untreated knee chondral injuries and compare it with matched controls. METHODS:
      All players with knee chondral injuries identified at the NFL Combine (2009-2015)
      were retrospectively reviewed. Players with prior knee surgery were excluded. A
      knee MRI for each player was reviewed; location, modified International Cartilage
      Repair Society (ICRS) grade (I-IV), and associated compartment subchondral edema
      were documented. Position, respective NFL Draft pick selection number, games
      started, played, snap percentage, and position-specific performance metrics
      during the first 2 NFL seasons were recorded for the injury and injury-free
      control group composed of players with (1) no prior knee injury, (2) no
      significant missed time prior to the NFL (<=2 total missed games in college), (3)
      no history of knee surgery, and (4) drafted in the respective NFL Draft following
      the NFL Combine. RESULTS: Of the 2,285 players reviewed, 101 (4.4%) had an injury
      without prior knee surgery. The patella (63.4%) and trochlea (34%) were most
      commonly affected. Defensive linemen were at highest risk for unrecognized
      injuries (odds ratio 1.8, P = .015). Players with previously untreated injuries,
      compared with controls, were picked later (mean pick: 125.8) and played (mean:
      23) and started (mean: 10.4) fewer games during the initial 2 NFL seasons (P <
      .001 for all). Particularly, subchondral bone edema and full-thickness cartilage
      injuries were associated with fewer games played (P = .003). CONCLUSIONS: The
      patellofemoral joint was most commonly affected in NFL Combine participants.
      Previously untreated knee articular injuries in players at the NFL Combine are
      associated with poorer early NFL performance in comparison to uninjured players.
      Subchondral bone edema and full-thickness cartilage injury on MRI were associated
      with fewer games played during the initial NFL career. LEVEL OF EVIDENCE: Level
      III, case-control study.

PMID- 29225016
TI  - Posterior Cruciate Ligament Injuries of the Knee at the National Football League
      Combine: An Imaging and Epidemiology Study.
AB  - PURPOSE: To determine the epidemiology by player position, examination, imaging
      findings, and associated injuries of posterior cruciate ligament (PCL) injuries
      in players participating in the National Football League (NFL) Combine. METHODS:
      All PCL injuries identified at the NFL Combine (2009-2015) were reviewed. Data
      were obtained from the database organized by the NFL medical personnel for the
      compilation of the medical and physical performance examination results of NFL
      Draftees participating in the NFL Combine from 2009 to 2015. Inclusion criteria
      were any player with clinical findings or a previous surgery consistent with a
      PCL injury who participated in the NFL Combine. RESULTS: Of the 2,285 players who
      participated in the NFL Combine between 2009 and 2015, 69 (3%) had evidence of a
      PCL injury, of which 11 players (15.9%) were managed surgically. On physical
      examination, 35 players (52%) had a grade II or III posterior drawer. Concomitant
      injuries were present frequently and included medial collateral ligament (MCL;
      42%), anterior cruciate ligament (ACL; 11.6%), and chondral injuries (31.8%),
      especially in the lateral tibiofemoral compartment. CONCLUSIONS: Three percent of
      the players at the NFL Combine presented with a PCL injury, with a significant
      amount being either running backs (14/69, 20.2%) or offensive linemen (14/69,
      20.2%). Approximately half of the players with a PCL tear had a residual grade II
      or III posterior drawer after sustaining a PCL injury. Concomitant injuries were
      present frequently and included MCL (42%), ACL (11.6%), and chondral injuries
      (31.8%), especially in the lateral tibiofemoral compartment. For those players
      with clinical concern for PCL ligamentous laxity, there should be a complete
      comprehensive workup that includes plain and PCL stress view radiographs, and
      magnetic resonance imaging. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29225017
TI  - Qualitative and Quantitative Anatomy of the Proximal Humerus Muscle Attachments
      and the Axillary Nerve: A Cadaveric Study.
AB  - PURPOSE: To provide a quantitative and qualitative anatomic analysis of the
      pectoralis major, teres major, and latissimus dorsi on the humerus, as well as
      the deltoid tendinous attachments on the proximal humerus and acromion, and to
      quantitatively characterize the humeral course of the axillary nerve. METHODS:
      Ten nonpaired, fresh-frozen human cadaveric shoulders were analyzed. A portable
      coordinate-measuring device quantified the location of bony landmarks and tendon
      attachment areas. The tendon footprints were recorded by tracing their outlines
      and center points. The footprint areas of the tendons, the distances between the
      footprint areas and pertinent osseous and soft-tissue landmarks, and the distance
      between where the axillary nerve courses across the humerus relative to the
      acromion and greater tuberosity were measured. RESULTS: Of the 10 specimens, 9
      (90%) had 5 distinct tendinous bands attaching the deltoid to the acromion; 1
      specimen had 4 bands. The distances between the center of the deltoid footprint
      on the humerus and the centers of the pectoralis major, latissimus dorsi, and
      teres major tendon footprints on the humerus were 43.5 mm, 58.5 mm, and 49.4 mm,
      respectively. The shortest distances from the perimeter of the pectoralis major
      to the latissimus dorsi and teres major tendon footprints were 3.9 mm and 9.5 mm,
      respectively. The distance from the superior aspect of the greater tuberosity to
      the axillary nerve on the humeral shaft was 50.3 mm (95% confidence interval,
      47.0-53.5 mm). The distance from the lateral acromion to the axillary nerve was
      69.3 mm (95% confidence interval, 64.1-74.5 mm). CONCLUSIONS: The deltoid muscle
      had 4 to 5 tendinous insertions on the acromion, and the axillary nerve was 50.3
      mm from the tip of the greater tuberosity. The distance between the lower border
      of the pectoralis major and the axillary nerve was 9.4 mm. CLINICAL RELEVANCE:
      Knowledge of the quantitative anatomy of the tendons of the proximal humerus and
      axillary nerve can aid in identifying structures of interest during open shoulder
      surgery and in avoiding iatrogenic axillary nerve injury. Furthermore, this study
      provides direction to avoid injury to the deltoid tendons during open surgery.

PMID- 29225018
TI  - Incidence and Changing Trends of Shoulder Stabilization in the United States.
AB  - PURPOSE: To determine the incidence and demographic characteristics of shoulder
      stabilization in the United States, with particular focus on age, sex, and
      inpatient versus outpatient treatment. METHODS: The National Hospital Discharge
      Survey and the National Survey of Ambulatory Surgery databases were searched
      using a combination of International Classification of Diseases, Ninth Revision
      diagnosis and procedure codes, encompassing open and arthroscopic shoulder
      stabilization procedures. Incidence was determined using National Survey of
      Ambulatory Surgery, National Hospital Discharge Survey, and US census data, and
      the results were stratified by age, sex, facility, and concomitant diagnoses.
      Data were analyzed between 1994 and 2006, the most recent year for which data are
      available within these sources. RESULTS: The incidence of shoulder stabilization
      in the United States was 5.84 per 100,000 person-years (n = 15,514; 95%
      confidence interval, 11,975-19,053) in 1994 to 1996 and 6.89 per 100,000 person
      years (n = 20,588; 95% confidence interval, 16,254-24,922) in 2006 (P = .0697).
      The number of inpatient procedures decreased significantly whereas the number of
      outpatient procedures increased significantly over the same period (P < .0001 for
      both). The incidence of stabilization increased in patients aged 45 to 64 years
      (P < .0001) and patients aged 65 years or older (P = .0008) but was unchanged in
      patients aged 44 years or younger (P = .4745). The average age of patients
      undergoing stabilization increased over the study period, from 30 years to 47
      years for inpatients (P = .01) and from 27 years to 34 years for ambulatory
      patients (P = .05). The incidence of stabilization increased significantly in
      male patients (P = .0075) but remained stable in female patients (P = .8057) over
      the same period. Diagnoses related to rotator cuff pathology and shoulder
      derangement were the most common concurrent diagnosis codes. CONCLUSIONS: The
      overall incidence of shoulder stabilization in the United States is 6.89 per
      100,000 person-years. The incidence increased by 18% between 1994 and 2006.
      During the study period, shoulder stabilization shifted to become a largely
      outpatient procedure, and the average age increased significantly. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 29225019
TI  - Primary Versus Revision Anterior Cruciate Ligament Reconstruction: Patient
      Demographics, Radiographic Findings, and Associated Lesions.
AB  - PURPOSE: The purpose of this study was to evaluate the differences in intra
      articular pathology, demographic characteristics, and radiographic
      characteristics of the knee associated with primary anterior cruciate ligament
      reconstruction (ACLR) versus revision ACLR at the time of initial presentation
      with either a native anterior cruciate ligament tear or an anterior cruciate
      ligament graft tear. Secondarily, we aimed to investigate risk factors for
      concomitant medial and lateral meniscal tears and cartilage injuries at the time
      of ACLR. METHODS: This was a retrospective review of patients who underwent
      primary or revision ACLR by a single surgeon. The exclusion criteria were as
      follows: skeletally immature patients; patients with an intra-articular fracture;
      patients with an ipsilateral knee infection; or patients who underwent an
      osteotomy, cartilage restoration procedure, or meniscal transplantation either
      previously or concomitantly with the ACLR. Detailed patient demographic data,
      radiographic long-standing alignment, tibial slope, and intraoperative findings
      including articular cartilage injury grade and meniscus integrity were documented
      at surgery. RESULTS: There were 487 patients included in this study (363 with
      primary ACLR and 124 with revision ACLR). There were no significant differences
      in age (P = .119), sex (P = .917), body mass index (P = .468), allograft versus
      autograft reconstruction (P = .916), or prevalence of meniscal tears (P = .142)
      between the primary and revision groups. Patients who underwent revision ACLR had
      a significantly increased medial tibial slope (P = .048) and a higher prevalence
      of chondral defects on both the medial (P < .001) and lateral (P = .003) femoral
      condyles when compared with primary ACLR patients. Logistic regression showed
      that a decreased tibial slope was correlated with femoral medial-sided chondral
      injuries and that varus or valgus coronal-plane malalignment was correlated with
      lateral meniscal tears in both groups. CONCLUSIONS: The findings of this study
      show that patients undergoing a revision ACLR have significantly more chondral
      lesions, as well as higher-grade chondral lesions, at the time of presentation.
      Furthermore, coronal malalignment and a decreased tibial slope may contribute to
      injury patterns of the lateral meniscus and medial compartment cartilage,
      respectively. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

PMID- 29225020
TI  - Arthroscopic Wafer Procedure Versus Ulnar Shortening Osteotomy as a Surgical
      Treatment for Idiopathic Ulnar Impaction Syndrome.
AB  - PURPOSE: To compare clinical and radiologic outcomes and complication rates of
      the arthroscopic wafer procedure (AWP) and ulnar shortening osteotomy (USO) for
      idiopathic ulnar impaction syndrome (UIS). METHODS: From May 2009 to June 2014,
      42 patients who were aged 45 years or older with idiopathic UIS underwent either
      the AWP or USO under the following identical surgical indications: (1) less than
      4 mm of positive ulnar variance, (2) Palmer classification 2C or 2D lesion of the
      triangular fibrocartilage complex, (3) stable distal radioulnar joint (DRUJ)
      and/or lunotriquetral joint, and (4) no evidence of osteoarthritis of the DRUJ or
      ulnocarpal joint. The patient assignment was not randomized. Were used a visual
      analog scale for ulnar wrist pain; grip strength; range of motion; the Mayo Wrist
      Score (MWS); and the Disabilities of the Arm, Shoulder and Hand (DASH) score at
      3, 6, 12, and 24 months after surgery to compare clinical outcomes. Ulnar
      variance, cystic changes of the lunate and triquetrum, and DRUJ arthritis on
      radiographs and operation-related complications were compared. RESULTS: This
      study evaluated 19 patients after the AWP and 23 patients after USO. At 3 months,
      the AWP produced significantly better outcomes than USO regarding grip strength
      (79.6% +/- 14.3% vs 62.7% +/- 12.6%, P < .001), MWS (81.8 +/- 7.9 points vs 71.3
      +/- 14.2 points, P = .005), and DASH score (19.4 +/- 8.4 vs 31.5 +/- 14.0, P =
      .001); clinical outcomes were similar at 6, 12, and 24 months. The complication
      rates were 34.8% for USO and 10.5% for the AWP; complications included DRUJ
      arthritis (n = 4), implant irritation (n = 6), and refracture after implant
      removal (n = 2) in the USO group and secondary surgery (n = 1) and tendinopathy
      (n = 1) in the AWP group. CONCLUSIONS: The AWP and USO for idiopathic UIS with
      subtle positive ulnar variance achieved similar clinical and radiologic outcomes
      at 2 years after surgery. However, compared with USO, the AWP showed lower
      complication rates and better grip strength, MWS values, and DASH scores at 3
      months after surgery. LEVEL OF EVIDENCE: Level III, comparative trial.

PMID- 29225021
TI  - Implications of Core and Hip Injuries on Major League Baseball Pitchers on the
      Disabled List.
AB  - PURPOSE: To investigate the frequency of core and hip injuries in Major League
      Baseball (MLB) pitchers and their impact on performance, workload, and pitch
      type. METHODS: Demographic, performance data, and injury data were acquired for
      330 MLB pitchers with 454 injuries placed on the disabled list (DL) from 2014 to
      2015 seasons. Core and hip/groin injuries were analyzed in which injury year data
      were compared with career data and against other injury groups. RESULTS: Core
      injuries represented 14% of all injuries and hip/groin injuries represented 7%.
      Average days on the DL for core injuries were 47.0 (standard deviation 5.6) days
      and 37.7 (standard deviation 8.1) days for hip/groin injuries. Return from the DL
      the same season for core injuries was 78% and 73% for hip/groin injuries. Core
      injuries returned to the DL 46% of the time (73% for noncore injuries) and
      hip/groin returned 56% of the time (60% for nonhip/groin injuries). No changes in
      workload were noted except starters with core injuries pitched less innings/game
      (5.3 vs 4.9 innings/game, P = .031) and more pitches/game (85.5 vs 78.4 pitches,
      P = .026). Fastball velocity decreased in the core injury group the year of
      injury (91.6 vs 92.2 mph, P = .001). Core injuries had slightly fewer home runs/9
      innings and fewer strikeouts/9 innings; hip/groin injuries had slightly more
      strikeouts/9 innings, with all other performance statistics no different between
      the groups including earned run average and wins above replacement. CONCLUSIONS:
      Core and hip injuries in MLB pitchers result in similar time on the DL compared
      with other injuries. Pitching workload during the year of injury does not seem to
      have a significant impact on sustaining a core or hip injury. Although there is a
      high rate of return to play from the DL, there is a high rate of reinjury in
      these pitchers more often for other injuries. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 29225022
TI  - The Mitotic Function of Augmin Is Dependent on Its Microtubule-Associated Protein
      Subunit EDE1 in Arabidopsis thaliana.
AB  - The augmin complex plays an essential role in microtubule (MT)-dependent MT
      nucleation by recruiting the gamma-tubulin complex to MT walls to generate new
      MTs [1]. The complex contains eight subunits (designated AUG) including AUG8,
      which is an MT-associated protein (MAP). When this complex is isolated from
      etiolated seedlings consisting of primarily interphase cells in Arabidopsis
      thaliana, AUG8 is an integral component [2]. EDE1 (Endosperm DEfective 1) is
      homologous to AUG8 [3]. Here, we demonstrate that EDE1, but not AUG8, is
      associated with acentrosomal spindle and phragmoplast MT arrays in patterns
      indistinguishable from those of the AUG1-7 subunits and the gamma-tubulin complex
      proteins (GCPs) that exhibit biased localization toward MT minus ends. Consistent
      with this colocalization, EDE1 directly interacts with AUG6 in vivo. Moreover, a
      partial loss-of-function mutation, ede1-1, compromises the localization of augmin
      and gamma-tubulin on the spindle and phragmoplast MT arrays and leads to serious
      distortions in spindle MT remodeling during mitosis. However, mitosis continues
      even when kinetochore fibers are not obviously discernable, and cytokinesis takes
      place following the formation of elongated bipolar phragmoplast MT arrays in the
      mutant. Hence, we conclude that the mitotic function of augmin is dependent on
      its MAP subunit EDE1, which cannot be replaced by AUG8, and that the cell-cycle
      dependent function of augmin can be differentially regulated by employing
      distinct MAP subunits. Our results also illustrate that plant cells can respond
      flexibly to serious challenges of compromised MT-dependent MT nucleation to
      complete mitosis and cytokinesis.

PMID- 29225023
TI  - Origins and Specification of the Drosophila Wing.
AB  - The insect wing is a key evolutionary innovation that was essential for insect
      diversification. Yet despite its importance, there is still debate about its
      evolutionary origins. Two main hypotheses have been proposed: the paranotal
      hypothesis, which suggests that wings evolved as an extension of the dorsal
      thorax, and the gill-exite hypothesis, which proposes that wings were derived
      from a modification of a pre-existing branch at the dorsal base (subcoxa) of the
      leg. Here, we address this question by studying how wing fates are initially
      specified during Drosophila embryogenesis, by characterizing a cis-regulatory
      module (CRM) from the snail (sna) gene, sna-DP (for dorsal primordia). sna-DP
      specifically marks the early primordia for both the wing and haltere,
      collectively referred to as the DP. We found that the inputs that activate sna-DP
      are distinct from those that activate Distalless, a marker for leg fates.
      Further, in genetic backgrounds in which the leg primordia are absent, the DP are
      still partially specified. However, lineage-tracing experiments demonstrate that
      cells from the early leg primordia contribute to both ventral and dorsal
      appendage fates. Together, these results suggest that the wings of Drosophila
      have a dual developmental origin: two groups of cells, one ventral and one more
      dorsal, give rise to the mature wing. We suggest that the dual developmental
      origins of the wing may be a molecular remnant of the evolutionary history of
      this appendage, in which cells of the subcoxa of the leg coalesced with dorsal
      outgrowths to evolve a dorsal appendage with motor control.

PMID- 29225024
TI  - At Birth, Humans Associate "Few" with Left and "Many" with Right.
AB  - Humans use spatial representations to structure abstract concepts [1]. One of the
      most well-known examples is the "mental number line"-the propensity to imagine
      numbers oriented in space [2, 3]. Human infants [4, 5], children [6, 7], adults
      [8], and nonhuman animals [9, 10] associate small numbers with the left side of
      space and large numbers with the right. In humans, cultural artifacts, such as
      the direction of reading and writing, modulate the directionality of this
      representation, with right-to-left reading cultures associating small numbers
      with right and large numbers with left [11], whereas the opposite association
      permeates left-to-right reading cultures [8]. Number-space mapping plays a
      central role in human mathematical concepts [12], but its origins remain unclear:
      is it the result of an innate bias or does it develop after birth? Infant humans
      are passively exposed to a spatially coded environment, so experience and culture
      could underlie the mental number line. To rule out this possibility, we tested
      neonates' responses to small or large auditory quantities paired with geometric
      figures presented on either the left or right sides of the screen. We show that 0
      to 3-day-old neonates associate a small quantity with the left and a large
      quantity with the right when the multidimensional stimulus contains discrete
      numerical information, providing evidence that representations of number are
      associated to an oriented space at the start of postnatal life, prior to
      experience with language, culture, or with culture-specific biases.

PMID- 29225026
TI  - Differential Effects of Climate on Survival Rates Drive Hybrid Zone Movement.
AB  - Climate change has been implicated as driving shifts of hybridizing species'
      range limits [1, 2]. Whether and how much hybrid zones move depends on the
      relative fitness of hybridzing species under changing conditions [3, 4]. However,
      fitness is rarely linked to both climatic conditions and movement of hybrid
      zones, such that the relationship between climate change and hybrid zone dynamics
      remains tenuous [5]. Here we report how interactions between climate (seasonal
      precipitation) and competitor densities result in steep differentials in
      survival, which in turn drive hybrid zone movement for two woodrat species
      (Neotoma fuscipes and N. macrotis) in central California, USA. Using 6 years of
      capture-mark-recapture data, we found that the smaller-bodied species, N.
      macrotis, and hybrids had survival advantages over the larger-bodied N. fuscipes
      in the contact region during dry winters and wet springs. This pattern of
      differential survival, with N. macrotis having a consistent advantage over N.
      fuscipes during our study period, matched the spatial dynamics of the hybrid
      zone, which moved steadily north into N. fuscipes territory, with its estimated
      center moving ~150 m north in 6 years. Our findings provide a unique
      demonstration of range movements emerging from a complex interplay between
      climate and competition. Although all study site areas experienced the same
      climatic conditions, competitive effects created a complex spatial pattern of
      survival differentials, which in turn influenced hybrid zone movement.
      Characterization of fitness differentials derived from replicated demographic
      studies of contact regions between competitors should greatly improve our ability
      to understand and forecast climate-driven range dynamics.

PMID- 29225027
TI  - Evolution of the Sauropterygian Labyrinth with Increasingly Pelagic Lifestyles.
AB  - Sauropterygia, a successful clade of marine reptiles abundant in aquatic
      ecosystems of the Mesozoic, inhabited nearshore to pelagic habitats over >180
      million years of evolutionary history [1]. Aquatic vertebrates experience strong
      buoyancy forces that allow movement in a three-dimensional environment, resulting
      in structural convergences such as flippers and fish-like bauplans [2, 3], as
      well as convergences in the sensory systems. We used computed tomographic scans
      of 19 sauropterygian species to determine how the transition to pelagic
      lifestyles influenced the evolution of the endosseous labyrinth, which houses the
      vestibular sensory organ of balance and orientation [4]. Semicircular canal
      geometries underwent distinct changes during the transition from nearshore
      Triassic sauropterygians to the later, pelagic plesiosaurs. Triassic
      sauropterygians have dorsoventrally compact, anteroposteriorly elongate
      labyrinths, resembling those of crocodylians. In contrast, plesiosaurs have
      compact, bulbous labyrinths, sharing some features with those of sea turtles.
      Differences in relative labyrinth size among sauropterygians correspond to
      locomotory differences: bottom-walking [5, 6] placodonts have proportionally
      larger labyrinths than actively swimming taxa (i.e., all other sauropterygians).
      Furthermore, independent evolutionary origins of short-necked, large-headed
      "pliosauromorph" body proportions among plesiosaurs coincide with reductions of
      labyrinth size, paralleling the evolutionary history of cetaceans [7].
      Sauropterygian labyrinth evolution is therefore correlated closely with both
      locomotory style and body proportions, and these changes are consistent with
      isolated observations made previously in other marine tetrapods. Our study
      presents the first virtual reconstructions of plesiosaur endosseous labyrinths
      and the first large-scale, quantitative study detailing the effects of
      increasingly aquatic lifestyles on labyrinth morphology among marine reptiles.

PMID- 29225025
TI  - Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling.
AB  - Sleep is an essential and evolutionarily conserved behavioral state whose
      regulation remains poorly understood. To identify genes that regulate vertebrate
      sleep, we recently performed a genetic screen in zebrafish, and here we report
      the identification of neuropeptide Y (NPY) as both necessary for normal daytime
      sleep duration and sufficient to promote sleep. We show that overexpression of
      NPY increases sleep, whereas mutation of npy or ablation of npy-expressing
      neurons decreases sleep. By analyzing sleep architecture, we show that NPY
      regulates sleep primarily by modulating the length of wake bouts. To determine
      how NPY regulates sleep, we tested for interactions with several systems known to
      regulate sleep, and provide anatomical, molecular, genetic, and pharmacological
      evidence that NPY promotes sleep by inhibiting noradrenergic signaling. These
      data establish NPY as an important vertebrate sleep/wake regulator and link NPY
      signaling to an established arousal-promoting system.

PMID- 29225028
TI  - Causes and Consequences of Tool Shape Variation in New Caledonian Crows.
AB  - Hominins have been making tools for over three million years [1], yet the
      earliest known hooked tools appeared as recently as 90,000 years ago [2]. Hook
      innovation is likely to have boosted our ancestors' hunting and fishing
      efficiency [3], marking a major transition in human technological evolution. The
      New Caledonian crow is the only non-human animal known to craft hooks in the wild
      [4, 5]. Crows manufacture hooked stick tools in a multi-stage process, involving
      the detachment of a branch from suitable vegetation; "sculpting" of a terminal
      hook from the nodal joint; and often additional adjustments, such as length
      trimming, shaft bending, and bark stripping [4, 6, 7]. Although tools made by a
      given population share key design features [4, 6, 8], they vary appreciably in
      overall shape and hook dimensions. Using wild-caught, temporarily captive crows,
      we experimentally investigated causes and consequences of variation in hook-tool
      morphology. We found that bird age, manufacture method, and raw-material
      properties influenced tool morphology, and that hook geometry in turn affected
      crows' foraging efficiency. Specifically, hook depth varied with both detachment
      technique and plant rigidity, and deeper hooks enabled faster prey extraction in
      the provided tasks. Older crows manufactured tools of distinctive shape, with
      pronounced shaft curvature and hooks of intermediate depth. Future work should
      explore the interactive effects of extrinsic and intrinsic factors on tool
      production and deployment. Our study provides a quantitative assessment of the
      drivers and functional significance of tool shape variation in a non-human
      animal, affording valuable comparative insights into early hominin tool crafting
      [9].

PMID- 29225030
TI  - A Rare Cause of Critical Limb Ischaemia: An Aneurysmal Persistent Sciatic Artery.

PMID- 29225029
TI  - Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5
      Expression and Time of Axon Initiation.
AB  - Many networks throughout the nervous system are organized into topographic maps,
      where the positions of neuron cell bodies in the projecting field correspond with
      the positions of their axons in the target field. Previous studies of topographic
      map development show evidence for spatial patterning mechanisms, in which
      molecular determinants expressed across the projecting and target fields are
      matched directly in a point-to-point mapping process. Here, we describe a novel
      temporal mechanism of topographic map formation that depends on spatially
      regulated differences in the timing of axon outgrowth and functions in parallel
      with spatial point-to-point mapping mechanisms. We focus on the vagus motor
      neurons, which are topographically arranged in both mammals and fish. We show
      that cell position along the anterior-posterior axis of hindbrain rhombomere 8
      determines expression of hox5 genes, which are expressed in posterior, but not
      anterior, vagus motor neurons. Using live imaging and transplantation in
      zebrafish embryos, we additionally reveal that axon initiation is delayed in
      posterior vagus motor neurons independent of neuron birth time. We show that hox5
      expression directs topographic mapping without affecting time of axon outgrowth
      and that time of axon outgrowth directs topographic mapping without affecting
      hox5 expression. The vagus motor neuron topographic map is therefore determined
      by two mechanisms that act in parallel: a hox5-dependent spatial mechanism akin
      to classic mechanisms of topographic map formation and a novel axon outgrowth
      dependent temporal mechanism in which time of axon formation is spatially
      regulated to direct axon targeting.

PMID- 29225031
TI  - Re: "Catheter Foam Sclerotherapy of Great Saphenous Vein, with Peri-saphenous
      Tumescence Infiltration and Saphenous Irrigation".

PMID- 29225032
TI  - Editor's Choice - Calcification of Thoracic and Abdominal Aneurysms is Associated
      with Mortality and Morbidity.
AB  - INTRODUCTION: Cardiovascular events are common in people with aortic aneurysms.
      Arterial calcification is a recognised predictor of cardiovascular outcomes in
      coronary artery disease. Whether calcification within abdominal and thoracic
      aneurysm walls is correlated with poor cardiovascular outcomes is not known.
      PATIENTS AND METHODS: Calcium scores were derived from computed tomography (CT)
      scans of consecutive patients with either infrarenal (AAA) or descending thoracic
      aneurysms (TAA) using the modified Agatston score. The primary outcome was
      subsequent all cause mortality during follow-up. Secondary outcomes were
      cardiovascular mortality and morbidity. RESULTS: A total of 319 patients (123 TAA
      and 196 AAA; median age 77 [71-84] years, 72% male) were included with a median
      follow-up of 30 months. The primary outcome occurred in 120 (37.6%) patients. In
      the abdominal aortic aneurysm group, the calcium score was significantly related
      to both all cause mortality and cardiac mortality (odds ratios (OR) of 2.246 (95%
      CI 1.591-9.476; p < 0.001) and 1.321 (1.076-2.762; p = 0.003)) respectively. In
      the thoracic aneurysm group, calcium score was significantly related to all cause
      mortality (OR 6.444; 95% CI 2.574-6.137; p < 0.001), cardiac mortality (OR 3.456;
      95% CI 1.765-4.654; p = 0.042) and cardiac morbidity (OR 2.128; 95% CI 1.973
      4.342; p = 0.002). CONCLUSIONS: Aortic aneurysm calcification, in either the
      thoracic or the abdominal territory, is significantly associated with both higher
      overall and cardiovascular mortality. Calcium scoring, rapidly derived from
      routine CT scans, may help identify high risk patients for treatment to reduce
      risk.

PMID- 29225034
TI  - Cytosolic Iron-Sulfur Assembly Is Evolutionarily Tuned by a Cancer-Amplified
      Ubiquitin Ligase.
AB  - The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway functions to
      incorporate inorganic Fe-S cofactors into a variety of proteins, including
      several DNA repair enzymes. However, the mechanisms regulating the CIA pathway
      are unknown. We describe here that the MAGE-F1-NSE1 E3 ubiquitin ligase regulates
      the CIA pathway through ubiquitination and degradation of the CIA-targeting
      protein MMS19. Overexpression or knockout of MAGE-F1 altered Fe-S incorporation
      into MMS19-dependent DNA repair enzymes, DNA repair capacity, sensitivity to DNA
      damaging agents, and iron homeostasis. Intriguingly, MAGE-F1 has undergone
      adaptive pseudogenization in select mammalian lineages. In contrast, MAGE-F1 is
      highly amplified in multiple human cancer types and amplified tumors have
      increased mutational burden. Thus, flux through the CIA pathway can be regulated
      by degradation of the substrate-specifying MMS19 protein and its downregulation
      is a common feature in cancer and is evolutionarily controlled.

PMID- 29225033
TI  - Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at
      Serine 249 and Consequent PIN1 Binding.
AB  - TP53 missense mutations significantly influence the development and progression
      of various human cancers via their gain of new functions (GOF) through different
      mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S
      (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma
      (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK
      inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts
      with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its
      nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans
      isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with
      mutations of four serines/threonines previously shown to be crucial for PIN1
      binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent
      rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1
      p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC.

PMID- 29225035
TI  - Cockayne's Syndrome A and B Proteins Regulate Transcription Arrest after
      Genotoxic Stress by Promoting ATF3 Degradation.
AB  - Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB
      proteins have been linked to both promoting transcription-coupled repair and
      restoring transcription following DNA damage. We show that UV stress arrests
      transcription of approximately 70% of genes in CSA- or CSB-deficient cells due to
      the constitutive presence of ATF3 at CRE/ATF sites. We found that CSB,
      CSA/DDB1/CUL4A, and MDM2 were essential for ATF3 ubiquitination and degradation
      by the proteasome. ATF3 removal was concomitant with the recruitment of RNA
      polymerase II and the restart of transcription. Preventing ATF3 ubiquitination by
      mutating target lysines prevented recovery of transcription and increased cell
      death following UV treatment. Our data suggest that the coordinate action of CSA
      and CSB, as part of the ubiquitin/proteasome machinery, regulates the recruitment
      timing of DNA-binding factors and provide explanations about the mechanism of
      transcription arrest following genotoxic stress.

PMID- 29225036
TI  - Transcription and Remodeling Produce Asymmetrically Unwrapped Nucleosomal
      Intermediates.
AB  - Nucleosomes are disrupted during transcription and other active processes, but
      the structural intermediates during nucleosome disruption in vivo are unknown. To
      identify intermediates, we mapped subnucleosomal protections in Drosophila cells
      using Micrococcal Nuclease followed by sequencing. At the first nucleosome
      position downstream of the transcription start site, we identified unwrapped
      intermediates, including hexasomes that lack either proximal or distal contacts.
      Inhibiting topoisomerases or depleting histone chaperones increased unwrapping,
      whereas inhibiting release of paused RNAPII or reducing RNAPII elongation
      decreased unwrapping. Our results indicate that positive torsion generated by
      elongating RNAPII causes transient loss of histone-DNA contacts. Using this
      mapping approach, we found that nucleosomes flanking human CTCF insulation sites
      are similarly disrupted. We also identified diagnostic subnucleosomal particle
      remnants in cell-free human DNA data as a relic of transcribed genes from
      apoptosing cells. Thus identification of subnucleosomal fragments from nuclease
      protection data represents a general strategy for structural epigenomics.

PMID- 29225037
TI  - Understanding and Sensitizing Density-Dependent Persistence to Quinolone
      Antibiotics.
AB  - Physiologic and environmental factors can modulate antibiotic activity and thus
      pose a significant challenge to antibiotic treatment. The quinolone class of
      antibiotics, which targets bacterial topoisomerases, fails to kill bacteria that
      have grown to high density; however, the mechanistic basis for this persistence
      is unclear. Here, we show that exhaustion of the metabolic inputs that couple
      carbon catabolism to oxidative phosphorylation is a primary cause of growth phase
      dependent persistence to quinolone antibiotics. Supplementation of stationary
      phase cultures with glucose and a suitable terminal electron acceptor to
      stimulate respiratory metabolism is sufficient to sensitize cells to quinolone
      killing. Using this approach, we successfully sensitize high-density populations
      of Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis to
      quinolone antibiotics. Our findings link growth-dependent quinolone persistence
      to discrete impairments in respiratory metabolism and identify a strategy to kill
      non-dividing bacteria.

PMID- 29225038
TI  - Cell Cycle Control by Nuclear Sequestration of CDC20 and CDH1 mRNA in Plant Stem
      Cells.
AB  - In eukaryotes, most RNA molecules are exported into the cytoplasm after
      transcription. Long noncoding RNAs (lncRNAs) reside and function primarily inside
      the nucleus, but nuclear localization of mRNAs has been considered rare in both
      animals and plants. Here we show that Arabidopsis anaphase-promoting
      complex/cyclosome (APC/C) coactivator genes CDC20 and CCS52B (CDH1 ortholog) are
      co-expressed with their target cyclin B genes (CYCBs) during mitosis. CYCB
      transcripts can be exported and translated; however, CDC20 and CCS52B mRNAs are
      confined to the nucleus at prophase, and the cognate proteins are not translated
      until the redistribution of the mRNAs to the cytoplasm after nuclear envelope
      breakdown (NEBD) at prometaphase. The 5' untranslated region (UTR) plays dual
      roles in CDC20 mRNA nuclear localization and translation. Mitotic accumulation of
      CDC20 and CCS52B transcripts enables the timely and rapid activation of APC/C,
      while the nuclear sequestration of these transcripts at prophase appears to
      protect cyclins from precocious degradation.

PMID- 29225039
TI  - A Massively Parallel Reporter Assay of 3' UTR Sequences Identifies In Vivo Rules
      for mRNA Degradation.
AB  - The stability of mRNAs is regulated by signals within their sequences, but a
      systematic and predictive understanding of the underlying sequence rules remains
      elusive. Here we introduce UTR-seq, a combination of massively parallel reporter
      assays and regression models, to survey the dynamics of tens of thousands of 3'
      UTR sequences during early zebrafish embryogenesis. UTR-seq revealed two temporal
      degradation programs: a maternally encoded early-onset program and a late-onset
      program that accelerated degradation after zygotic genome activation. Three
      signals regulated early-onset rates: stabilizing poly-U and UUAG sequences and
      destabilizing GC-rich signals. Three signals explained late-onset degradation:
      miR-430 seeds, AU-rich sequences, and Pumilio recognition sites. Sequence-based
      regression models translated 3' UTRs into their unique decay patterns and
      predicted the in vivo effect of sequence signals on mRNA stability. Their
      application led to the successful design of artificial 3' UTRs that conferred
      specific mRNA dynamics. UTR-seq provides a general strategy to uncover the rules
      of RNA cis regulation.

PMID- 29225040
TI  - Differential neuromodulatory role of endocannabinoids in the rodent trigeminal
      sensory ganglion and cerebral cortex relevant to pain processing.
AB  - Endocannabinoids are suggested to control pain, even though their clinical use is
      not fully validated and the underlying mechanisms are incompletely understood. To
      clarify the targets of endocannabinoid actions, we studied how activation of the
      endocannabinoid CB1 receptor (CB1R) affects neuronal responses in two in vitro
      preparations of rodents, namely the trigeminal sensory ganglion (TG) in culture
      and a coronal slice of the cerebral cortex. On TG small-medium size neurons, we
      tested whether submicromolar concentrations of the endogenous CB1R agonist
      anandamide (AEA) modulated inhibitory GABAA receptors and excitatory ATP-gated
      P2X3 receptors. AEA reversibly depressed GABA-mediated membrane currents without
      altering P2X3 receptor responses. The AEA antagonism was non-competitive,
      prevented by the CB1R antagonist AM-251, mimicked by the other cannabinoids 2
      arachidonylglycerol and WIN 55,212-2, and insensitive to TRPV1 blocker
      capsazepine. AEA inhibited the potentiation of GABAergic responses by the cAMP
      activator forskolin, in line with the canonical inhibition of cAMP synthesis by
      CB1Rs. In the cerebral cortex, AEA or WIN 55,212-2 did not affect electrically
      evoked local field potentials or characteristics of cortical spreading
      depolarization (CSD) elicited by high potassium application. The GABAA receptor
      blocker gabazine, however, strongly enhanced field potentials without affecting
      CSD properties, suggesting that CSD was not dominantly controlled by GABAergic
      mechanisms. Our data propose that, despite the widespread expression of CB1Rs
      peripherally and centrally, the functional effects of AEA are region-specific and
      depend on CB1R coupling to downstream effectors. Future studies concerned with
      the mechanisms of AEA analgesia should perhaps be directed to discrete
      subcortical nuclei processing trigeminal inputs.

PMID- 29225041
TI  - Syringaresinol suppresses excitatory synaptic transmission and picrotoxin-induced
      epileptic activity in the hippocampus through presynaptic mechanisms.
AB  - Many neuromodulating drugs acting on the nervous system originate from botanical
      sources. These plant-derived substances modulate the activity of receptors, ion
      channels, or transporters in neurons. Their properties make the substances useful
      for medicine and research. Here, we show that the plant lignan (+)-syringaresinol
      (SYR) suppresses excitatory synaptic transmission via presynaptic modulation.
      Bath application of SYR rapidly reduced the slopes of the field excitatory
      postsynaptic potentials (fEPSPs) at the hippocampal Schaffer collateral (SC)-CA1
      synapse in a dose-dependent manner. SYR preferentially affected excitatory
      synapses, while inhibitory synaptic transmission remained unchanged. SYR had no
      effect on the conductance or the desensitization of AMPARs but increased the
      paired-pulse ratios of synaptic responses at short (20-200 ms) inter-stimulus
      intervals. These presynaptic changes were accompanied by a reduction of the
      readily releasable pool size. Pretreatment of hippocampal slices with the Gi/o
      protein inhibitor N-ethylmaleimide (NEM) abolished the effect of SYR on
      excitatory synaptic transmission, while the application of SYR significantly
      decreased Ca2+ currents and hyperpolarized the resting membrane potentials of
      hippocampal neurons. In addition, SYR suppressed picrotoxin-induced epileptiform
      activity in hippocampal slices. Overall, our study identifies SYR as a new
      neuromodulating agent and suggests that SYR suppresses excitatory synaptic
      transmission by modulating presynaptic transmitter release.

PMID- 29225042
TI  - Endogenous dopamine and endocannabinoid signaling mediate cocaine-induced
      reversal of AMPAR synaptic potentiation in the nucleus accumbens shell.
AB  - Repeated exposure to drugs of abuse alters the structure and function of neural
      circuits mediating reward, generating maladaptive plasticity in circuits critical
      for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated
      exposure to cocaine induces progressive alterations in AMPAR-mediated
      glutamatergic synaptic transmission. During a 10-14 day period of abstinence from
      cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc)
      medium spiny neurons (MSNs), promoting a state of heightened synaptic
      excitability. Re-exposure to cocaine during abstinence, however, rapidly reverses
      and depotentiates enhanced AMPAR signaling. To understand how re-exposure to
      cocaine alters AMPAR synaptic transmission, we investigated the roles of dopamine
      and endocannabinoid (eCB) signaling in modifying synaptic strength in the NAc
      shell. Using patch-clamp recordings from NAc slices prepared after 10-14 days of
      abstinence from repeated cocaine, we found that AMPAR-mediated depotentiation is
      rapidly induced in the NAc shell within 20 min of cocaine re-exposure ex vivo,
      and persists for up to five days before synapses return to levels of potentiation
      observed during abstinence. In cocaine-treated animals, global dopamine receptor
      activation was both necessary and sufficient for the cocaine-evoked
      depotentiation of AMPAR synaptic function. Additionally, we identified that CB1
      receptors are engaged by endogenous endocannabinoids (eCBs) during re-exposure to
      cocaine ex vivo. Overall, these results indicate the central role that dopamine
      and eCB signaling mechanisms play in modulating cocaine-induced AMPAR plasticity
      in the NAc shell.

PMID- 29225043
TI  - Neurogranin in the nucleus accumbens regulates NMDA receptor tolerance and
      motivation for ethanol seeking.
AB  - Dysfunction of N-methyl-d-aspartate receptor (NMDAR) signaling in the nucleus
      accumbens (NAc) has been implicated in the pathophysiology of alcohol use
      disorders (AUD). Neurogranin (Ng), a calmodulin-binding protein, is exclusively
      expressed in the post-synapse, and mediates NMDAR driven synaptic plasticity by
      regulating the calcium-calmodulin (Ca2+-CaM) pathway. To study the functional
      role of Ng in AUD, we administrated behavior tests including Pavlovian instrument
      transfer (PIT), operant conditioning, and rotarod test using Ng null mice (Ng-/-
      mice). We used adeno-associated virus (AAV)-mediated Ng expression and
      pharmacological manipulation to validate behavioral responses in Ng-/- mice. The
      results from our multidisciplinary approaches demonstrated that deficit of Ng
      increases tolerance to NMDAR inhibition and elicit faster cue reactivity during
      PIT without changes in ethanol reward. Operant conditioning results demonstrated
      that Ng-/- mice self-administered significantly more ethanol and displayed
      reduced sensitivity to aversive motivation. We identified that ethanol exposure
      decreases mGluR5 (metabotropic glutamate receptor 5) expression in the NAc of Ng
      /- mice and pharmacological inhibition of mGluR5 reverses NMDAR desensitization
      in Ng-/- mice. Together these findings specifically suggest that accumbal Ng
      plays an essential role in the counterbalance between NMDAR and mGluR5 signaling;
      which alters NMDAR resistance, and thereby altering aversive motivation for
      ethanol and may ultimately contribute to susceptibility for alcohol addiction.

PMID- 29225044
TI  - Fear extinction in an obsessive-compulsive disorder animal model: Influence of
      sex and estrous cycle.
AB  - Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition that affects
      men and women equally, but with a sexually dimorphic pattern of development.
      Reproductive cycle events can influence symptom severity of OCD in females,
      indicating that ovarian hormones or their interaction with distinct
      neurotransmitter systems may play a role in OCD pathophysiology. Clinical studies
      and animal models have confirmed the importance of the serotonergic (5-HT) system
      in the neurobiology and treatment of OCD. Accordingly, the non-selective 5-HT2c
      agonist, meta-chlorophenylpiperazine (mCPP), exacerbates symptoms in untreated
      OCD patients. In rodents, it evokes repetitive behaviors that engage brain areas
      that are homologous with those found to be dysfunctional in OCD patients. These
      regions, including the medial prefrontal and anterior cingulate cortices, are
      also involved in fear inhibition, which is impaired in OCD. Here, we treated rats
      with mCPP (0.5 and 3.0 mg/kg) to evaluate its influence on self-grooming behavior
      and assess potential fear extinction retention deficits, taking into account sex
      differences and females' estrous cycle. We found that mCPP exacerbated grooming
      in male and female rats, irrespective of the estrous cycle phase. Fear extinction
      retention, however, was impaired only in females. Moreover, females undergoing
      fear extinction training during the metestrus/diestrus phases of the estrous
      cycle were more sensitive to the impairments induced by mCPP. Our results
      indicate that mCPP can induce OCD-like symptoms, exacerbating self-grooming and
      impairing fear extinction. It suggests that changes in 5-HT signaling through 5
      HT2c receptors may have an important role in the OCD pathophysiology and that the
      influence of gonadal hormones in OCD should be further investigated.

PMID- 29225045
TI  - Post-reexposure administration of riluzole attenuates the reconsolidation of
      conditioned fear memory in rats.
AB  - Recently, we demonstrated that riluzole, which has been shown to block the
      glutamatergic system, facilitates fear extinction in rats. Here, we undertook
      experiments on contextual fear conditioning to clarify the actions of riluzole on
      the reconsolidation of fear memory in rats. We used the fast-acting
      benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We
      demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the
      reconsolidation of contextual fear memory. Results from spontaneous recovery
      experiments also suggested that riluzole attenuated reconsolidation. Indeed,
      conditioned fear did not recover spontaneously 4 weeks after a short (3 min)
      reexposure and riluzole administration, whereas it recovered after a long (10
      min) reexposure. Using western blotting, we demonstrated that a short reexposure
      increased the phosphorylation of cyclic adenosine monophosphate response element
      binding protein significantly in the dorsal part of hippocampus, but not in the
      medial prefrontal cortex. Interestingly, this phosphorylation was attenuated by
      riluzole with short reexposure. In addition, bilateral microinjection of riluzole
      (2 MUM/0.2 MUl/side) directly into the dorsal hippocampus clearly attenuated the
      reconsolidation. These findings suggested that the attenuating effect of riluzole
      on the reconsolidation of fear memory involves, at least in part, the dorsal part
      of the hippocampus. In conclusion, we demonstrated that riluzole attenuates the
      reconsolidation of fear memory in rats.

PMID- 29225046
TI  - High-level expression and immunogenicity of porcine circovirus type 2b capsid
      protein without nuclear localization signal expressed in Hansenula polymorpha.
AB  - Currently, porcine circovirus type 2b (PCV2b) is the dominant PCV2 genotype
      causing postweaning multisystemic wasting disease (PMWS) in pigs worldwide.
      Efforts have been made to develop various recombinant capsid proteins of PCV2b
      used in vaccines against PCV2b. However, the nuclear localization signal (NLS) of
      PCV2b capsid protein (CP) was found to inhibit the expression of the whole length
      capsid protein in E.coli. Here, we expressed a NLS-deleted capsid protein
      (DeltaCP) of PCV2b in Hansenula polymorpha based on the capsid protein of PCV2b
      strain Y-7 isolated in China. Comparatively, the DeltaCP was expressed at a
      higher level than the CP. The purified DeltaCP could self-assemble into virus
      like particles (VLPs) with similar morphology of the VLPs formed by CP. The
      purified DeltaCP could be recognized by the anti-sera derived from the mice
      immunized by inactivated PCV2b particles. Furthermore, it induced higher levels
      of PCV2b specific antibodies than the purified CP in mice. These results showed
      that the DeltaCP, a recombinant PCV2b capsid protein without nuclear localization
      signal sequence, could be efficiently expressed in Hansenula polymorpha, and used
      as a candidate antigen for the development of PCV2b vaccines.

PMID- 29225047
TI  - MALDI-TOF MS analysis as a useful tool for an identification of Legionella
      pneumophila, a facultatively pathogenic bacterium interacting with free-living
      amoebae: A case study from water supply system of hospitals in Bratislava
      (Slovakia).
AB  - Legionellae, i.e. Legionella pneumophila, are human bacterial hydrophilic
      facultative pathogens causing pneumonia (Legionnaires' disease). Free-living
      amoebae (FLA) can serve as natural hosts and thus as reservoirs of many amoebae
      resistant bacteria. An encysted amoeba can contribute to the resistance of
      intracellular L. pneumophila to various chemical and physical treatments. Humans
      can be infected by droplets containing bacteria from an environmental source or
      human-made devices such as shower heads, bathtubs, air-conditioning units or
      whirlpools. In this study, we were investigating the presence of FLA and L.
      pneumophila in plumbing systems of healthcare facilities in Bratislava (Slovakia)
      by standard diagnostic methods, while the presence of L. pneumophila was verified
      also by MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry) analysis. The results showed the occurrence of L. pneumophila
      and FLA in 62.26% and 66.4% of samples taken from four paediatric clinics,
      respectively. Both standard methods and MALDI-TOF MS showed comparable results
      and they can be successfully applied for the identification of L. pneumophila
      strains in environmental samples. Our approach could be useful for further
      monitoring, prevention and decreasing risk of Legionella infection also in other
      hospitals.

PMID- 29225048
TI  - De novo assembly and functional annotations of the transcriptome of Metorchis
      orientalis (trematoda: Opisthorchiidae).
AB  - Metorchis orientalis is a neglected zoonotic parasite, living in the gallbladder
      and bile duct of poultry and some mammals as well as humans. In spite of its
      economic and medical importance, the information known about the transcriptome
      and genome of M. orientalis is limited. In this study, we performed de novo
      sequencing, transcriptome assembly and functional annotations of the adult M.
      orientalis, obtained about 77.4 million high-quality clean reads, among which the
      length of the transcript contigs ranged from 100 to 11,249 nt with mean length of
      373 nt and N50 length of 919 nt. We then assembled 31,943 unigenes, of which
      20,009 (62.6%) were annotated by BLASTn and BLASTx searches against the available
      database. Among these unigenes, 19,795 (62.0%), 3407 (10.7%), 10,620 (33.2%) of
      them had significant similarity in the NR, NT and Swiss-Prot databases,
      respectively; 5744 (18.0%) and 4678 (14.6%) unigenes were assigned to GO and COG,
      respectively; and 9099 (28.5%) unigenes were identified and mapped onto 256
      pathways in the KEGG Pathway database. Furthermore, we found that 98 (1.08%)
      unigenes were related to bile secretion and 5 (0.05%) to primary bile acid
      biosynthesis pathways category. The characterization of these transcriptomic data
      has implications for the better understanding of the biology of M. orientalis,
      and will facilitate the development of intervention agents for this and other
      pathogenic flukes of human and animal health significance.

PMID- 29225049
TI  - Oxidative stress and Na,K-ATPase activity differential regulation in brainstem
      and forebrain of Wistar Audiogenic rats may lead to increased seizure
      susceptibility.
AB  - The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred
      rodent strain that, when acutely stimulated with high-intensity sounds, develops
      brainstem-dependent tonic-clonic seizures that can evolve to limbic-like,
      myoclonic (forebrain) seizures when the acoustic stimuli are presented
      chronically (audiogenic kindling). In order to investigate possible mechanisms
      underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca
      ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative
      stress markers in whole forebrain and whole brainstem samples of naive WAR, as
      compared to samples from control Wistar rats. We also evaluated the expression
      levels of alpha1 and alpha3 isoforms of Na,K-ATPase in forebrain samples. We
      observed increased Na,K-ATPase activity in forebrain samples and increased
      oxidative stress markers (lipid peroxidation, glutathione peroxidase and
      superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg
      ATPase activity, lipid membrane composition and expression levels of alpha1 and
      alpha3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing
      that the membrane potentials from naive WAR's neurons are less negative than that
      from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity
      might be involved in a compensatory mechanism necessary to maintain WAR's brains
      normal activity. Additionally, ongoing oxidative stress in the brainstem could
      bring Na,K-ATPase activity back to normal levels, which may explain why WAR's
      present increased susceptibility to seizures triggered by high-intensity sound
      stimulation.

PMID- 29225050
TI  - Inhibition of the mitochondrial calcium uniporter prevents IL-13 and allergen
      mediated airway epithelial apoptosis and loss of barrier function.
AB  - Mitochondria are increasingly recognized as key mediators of acute cellular
      stress responses in asthma. However, the distinct roles of regulators of
      mitochondrial physiology on allergic asthma phenotypes are currently unknown. The
      mitochondrial Ca2+ uniporter (MCU) resides in the inner mitochondrial membrane
      and controls mitochondrial Ca2+ uptake into the mitochondrial matrix. To
      understand the function of MCU in models of allergic asthma, in vitro and in vivo
      studies were performed using models of functional deficiency or knockout of MCU.
      In primary human respiratory epithelial cells, MCU inhibition abrogated
      mitochondrial Ca2+ uptake and reactive oxygen species (ROS) production, preserved
      the mitochondrial membrane potential and protected from apoptosis in response to
      the pleiotropic Th2 cytokine IL-13. Consequently, epithelial barrier function was
      maintained with MCU inhibition. Similarly, the endothelial barrier was preserved
      in respiratory epithelium isolated from MCU-/- mice after exposure to IL-13. In
      the ovalbumin-model of allergic airway disease, MCU deficiency resulted in
      decreased apoptosis within the large airway epithelial cells. Concordantly,
      expression of the tight junction protein ZO-1 was preserved, indicative of
      maintenance of epithelial barrier function. These data implicate mitochondrial
      Ca2+ uptake through MCU as a key controller of epithelial cell viability in acute
      allergic asthma.

PMID- 29225051
TI  - gamma-Taxilin temporally regulates centrosome disjunction in a Nek2A-dependent
      manner.
AB  - Never in mitosis A-related kinase 2A (Nek2A), a centrosomal serine/threonine
      kinase, is involved in mitotic progression by regulating the centrosome cycle.
      Particularly, Nek2A is necessary for dissolution of the intercentriole linkage
      between the duplicated centrosomes prior to mitosis. Nek2A activity roughly
      parallels its cell cycle-dependent expression levels, but the precise mechanism
      regulating its activity remains unclear. In this study, we found that gamma
      taxilin co-localized with Nek2A at the centrosome during interphase and
      interacted with Nek2A in yeast two-hybrid and pull-down assays and that gamma
      taxilin regulated centrosome disjunction in a Nek2A-dependent manner. gamma
      Taxilin depletion increased the number of cells with striking splitting of
      centrosomes. The precocious splitting of centrosomes induced by gamma-taxilin
      depletion was attenuated by Nek2A depletion, suggesting that gamma-taxilin
      depletion induces the Nek2A-mediated dissolution of the intercentriole linkage
      between the duplicated centrosomes nevertheless mitosis does not yet begin. Taken
      together with the result that gamma-taxilin protein expression levels were
      decreased at the onset of mitosis, we propose that gamma-taxilin participates in
      Nek2A-mediated centrosome disjunction as a negative regulator through its
      interaction with Nek2A.

PMID- 29225053
TI  - Electronic consults for improving vancomycin use.

PMID- 29225052
TI  - Supersulfated low-molecular weight heparin synergizes with IGF1R/IR inhibitor to
      suppress synovial sarcoma growth and metastases.
AB  - Synovial sarcoma (SS) is an aggressive tumor with propensity for lung metastases
      which significantly impact patients' prognosis. New therapeutic approaches are
      needed to improve treatment outcome. Targeting the heparanase/heparan sulfate
      proteoglycan system by heparin derivatives which act as heparanase
      inhibitors/heparan sulfate mimetics is emerging as a therapeutic approach that
      can sensitize the tumor response to chemotherapy. We investigated the therapeutic
      potential of a supersulfated low molecular weight heparin (ssLMWH) in preclinical
      models of SS. ssLMWH showed a potent anti-heparanase activity, dose-dependently
      inhibited SS colony growth and cell invasion, and downregulated the activation of
      receptor tyrosine kinases including IGF1R and IR. The combination of ssLMWH and
      the IGF1R/IR inhibitor BMS754807 synergistically inhibited proliferation of cells
      exhibiting IGF1R hyperactivation, also abrogating cell motility and promoting
      apoptosis in association with PI3K/AKT pathway inhibition. The drug combination
      strongly enhanced the antitumor effect against the CME-1 model, as compared to
      single agent treatment, abrogating orthotopic tumor growth and significantly
      repressing spontaneous lung metastatic dissemination in treated mice. These
      findings provide a strong preclinical rationale for developing drug regimens
      combining heparanase inhibitors/HS mimetics with IGF1R antagonists for treatment
      of metastatic SS.

PMID- 29225055
TI  - Surgical antisepsis of hands: a two-step procedure with chlorhexidine to surpass
      the EN 12791.

PMID- 29225054
TI  - Clinical efficacy of seasonal influenza vaccination: characteristics of two
      outbreaks of influenza A(H1N1) in immunocompromised patients.
AB  - BACKGROUND: Influenza A(H1N1) causes serious complications in immunocompromised
      patients. The efficacy of seasonal vaccination in these patients has been
      questioned. AIM: To describe two outbreaks of influenza A(H1N1) in
      immunocompromised patients. METHODS: Two outbreaks of influenza A(H1N1) occurred
      in our institution: on the kidney transplant ward in 2014 including patients
      early after kidney or simultaneous pancreas-kidney transplantation, and on the
      oncology ward in 2016 including patients receiving chemotherapy for malignant
      tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal
      influenza vaccination were analysed. FINDINGS: Altogether 86 patients were
      exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal
      influenza vaccination status was unknown in 10. Only three out of 38 vaccinated
      patients were infected with influenza A(H1N1), compared with 20 out of 38
      unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients
      was associated with influenza, compared with seven out of 38 unvaccinated
      patients (P = 0.06). Shared factors behind the two outbreaks included outdated
      facilities not designed for the treatment of immunosuppressed patients.
      Vaccination coverage among patients was low, between 40% and 70% despite
      vaccination being offered to all patients free of charge. Vaccination coverage of
      healthcare workers on the transplant ward was low (46%), but, despite high
      coverage on the oncology ward (92%), the outbreak occurred. CONCLUSION: Seasonal
      influenza vaccination was clinically effective with both a reduced risk of
      influenza infection and a trend towards reduced mortality in these
      immunocompromised patients. Several possible causes were identified behind these
      two outbreaks, requiring continuous awareness in healthcare professionals to
      prevent further outbreaks.

PMID- 29225056
TI  - Radical Nephrectomy with or without Lymph Node Dissection for High Risk
      Nonmetastatic Renal Cell Carcinoma: A Multi-Institutional Analysis.
AB  - PURPOSE: Lymph node dissection may benefit patients at increased risk for lymph
      node metastases from renal cell carcinoma. Therefore, we evaluated the
      association of lymph node dissection with survival in patients at high risk
      undergoing radical nephrectomy for renal cell carcinoma. MATERIALS AND METHODS:
      We identified 2,722 patients with M0 renal cell carcinoma who underwent radical
      nephrectomy with or without lymph node dissection at 2 international centers from
      1990 to 2010. The associations of lymph node dissection with the development of
      distant metastases, and cancer specific and all cause mortality were evaluated
      using propensity score techniques and traditional multivariable Cox regression.
      Subset analyses were done to examine patients at increased risk of lymph node
      metastases. RESULTS: Overall 171 patients (6.3%) had pN1 disease. Median followup
      was 9.6 years. Clinicopathological features were well balanced after propensity
      score adjustment. Lymph node dissection was not significantly associated with a
      reduced risk of distant metastases, or cancer specific or all cause mortality in
      the overall cohort, among patients with preoperative radiographic lymphadenopathy
      (cN1), or across an increasing probability of pN1 disease from 0.10 or greater to
      0.50 or greater. Neither extended lymph node dissection nor the extent of lymph
      node dissection was associated with improved oncologic outcomes. CONCLUSIONS: The
      current analysis of a large, international cohort indicates that lymph node
      dissection is not associated with improved oncologic outcomes among patients at
      high risk who undergo radical nephrectomy for M0 renal cell carcinoma. This
      includes patients with radiographic lymphadenopathy (cN1) and across increasing
      probability thresholds of pN1 disease.

PMID- 29225057
TI  - Comparison of Pathological and Oncologic Outcomes of Favorable Risk Gleason Score
      3 + 4 and Low Risk Gleason Score 6 Prostate Cancer: Considerations for Active
      Surveillance.
AB  - PURPOSE: Recent NCCN(r) (National Comprehensive Cancer Network(r)) Guidelines(r)
      show that patients with biopsy Gleason score 3 + 4/Grade Group 2 but otherwise
      favorable features are active surveillance candidates. However, little is known
      about the long-term outcomes compared to that in men in the low risk Gleason
      score 6/Grade Group 1 group. We sought to clarify the risk of adverse features
      and oncologic outcomes in surgically treated, favorable Grade Group 2 vs 1 cases.
      MATERIALS AND METHODS: We queried our prospectively maintained radical
      prostatectomy database for all 8,095 patients with biopsy Grade Group 1 or 2
      prostate cancer who otherwise fulfilled the NCCN low risk definition of prostate
      specific antigen less than 10 ng/ml and cT2a or less, and who underwent radical
      prostatectomy from 1987 to 2014. Multivariable logistic regression and Kaplan
      Meier methods were used to compare pathological and oncologic outcomes. RESULTS:
      Organ confined disease was present in 93.9% and 82.6% of Grade Group 1 and
      favorable intermediate risk Grade Group 2 cases while seminal vesicle invasion
      was noted in 1.7% and 4.7%, and nodal disease was noted in 0.3% and 1.8%,
      respectively (all p <0.0001). On multivariable logistic regression biopsy proven
      Grade Group 2 disease was associated with a threefold greater risk of nonorgan
      confined disease (OR 3.1, 95% CI 1.7-5.7, p <0.001). The incidence of late
      treatment (more than 90 days from surgery) in Grade Group 1 vs 2 was 3.1% vs 8.5%
      for hormonal therapy and 6.0% vs 12.2% for radiation (p <0.001). In the Grade
      Group 1 vs 2 cohorts the 10-year biochemical recurrence-free survival rate was
      88.9% vs 81.2% and the 10-year systemic progression-free survival rate was 99% vs
      96.5% (each p <0.001). CONCLUSIONS: Men at favorable risk with Grade Group 2
      disease who are considering active surveillance should be informed of the risks
      of harboring adverse pathological features which impact secondary therapies and
      an increased risk of cancer progression.

PMID- 29225058
TI  - Impact of Comorbidities on Functional Recovery from Partial Nephrectomy.
AB  - PURPOSE: Parenchymal mass preservation, and ischemia type and/or duration can
      influence functional recovery after partial nephrectomy. Some groups have
      hypothesized that relevant comorbidities may also impact nephron stability and
      functional recovery but this has not been adequately investigated. MATERIALS AND
      METHODS: At our center 405 patients treated with partial nephrectomy from 2007 to
      2015 had the necessary data to determine the function and parenchymal mass
      preserved in the ipsilateral kidney. Comorbidities potentially associated with
      renal functional status were reviewed, including various degrees of hypertension,
      diabetes, cardiovascular disease, obesity, smoking status and related
      medications. Multivariable linear regression was done to assess factors
      associated with functional recovery, defined as the percent of preserved
      ipsilateral glomerular filtration rate. RESULTS: Median tumor size was 3.5 cm and
      the median R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor
      to collecting system or sinus, anterior/posterior, location relative to polar
      lines and tumor touching main renal artery or vein) score was 8. Warm and cold
      ischemia were done in 264 (65%) and 141 patients for a median duration of 21 and
      27 minutes, respectively. The median preserved ipsilateral glomerular filtration
      rate was 79%. Patient age, comorbidity index, hypertension and proteinuria were
      each associated with the preoperative glomerular filtration rate (all p <0.01).
      On univariable and multivariable analyses the preserved parenchymal mass, and
      ischemia type and duration were significantly associated with functional recovery
      (all p <0.001). On univariable analysis of comorbidities only hypertension was
      significantly associated with functional recovery. However, on multivariable
      analysis none of the analyzed comorbidities were associated with functional
      recovery. CONCLUSIONS: Recovery of function after partial nephrectomy depends
      primarily on parenchymal mass preservation and ischemia characteristics.
      Comorbidities failed to be associated with functional outcomes. Comorbidities can
      impact function, leading to surgery, and may influence long-term functional
      stability. However, our data suggest that they do not influence short-term
      recovery after partial nephrectomy.

PMID- 29225059
TI  - Effect of Music on Outpatient Urological Procedures: A Systematic Review and Meta
      Analysis from the European Association of Urology Section of Uro-Technology.
AB  - PURPOSE: Music is a practical, inexpensive and harmless analgesic and anxiolytic.
      An increasing number of original studies have been performed to investigate its
      potential application in urology. Our aim was to identify the effect of music on
      outpatient based urological procedures. MATERIALS AND METHODS: We systematically
      reviewed the effect of using music during all reported outpatient urology
      procedures, including transrectal ultrasound guided prostate biopsy, shock wave
      lithotripsy, urodynamic studies, percutaneous nephrostomy tube placement and
      cystoscopy. Data were included on all randomized trials from 1980 to 2017 and no
      language restrictions were applied. RESULTS: Included in analysis were 16
      randomized studies in which 972 of 1,950 patients (49.8%) were exposed to music
      during an outpatient procedure. The procedures included transrectal ultrasound
      guided prostate biopsy in 4 studies in a total of 286 patients, shock wave
      lithotripsy in 6 studies in a total of 1,023, cystoscopy in 3 studies in a total
      of 331, urodynamics in 2 studies in a total of 210 and percutaneous nephrostomy
      in 1 study in a total of 100. All studies incorporated a visual analog score to
      measure pain. Anxiety was measured by STAI (State-Trait Anxiety Inventory) in 13
      studies and by a visual analog scale in 2. While 14 of the 16 studies showed a
      reduction in self-reported pain, a reduction in anxiety was seen in 14. When
      using music, overall procedural satisfaction was better in 9 studies and patient
      willingness to repeat the procedure was also higher in 7. Our meta-analysis
      revealed a significant reduction in visual analog scale and STAI findings across
      all studies (p <0.001). CONCLUSIONS: Our systematic review demonstrated a
      beneficial effect of music on urological outpatient procedures. Music seemed to
      decrease anxiety and pain. It might serve as a useful adjunct to increase
      procedural satisfaction and patient willingness to undergo the procedure again.

PMID- 29225060
TI  - Functional Recovery, Oncologic Outcomes and Postoperative Complications after
      Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the
      Retzius Sparing and Standard Approaches.
AB  - PURPOSE: We report a 1-year update of functional urinary and sexual recovery,
      oncologic outcomes and postoperative complications in patients who completed a
      randomized controlled trial comparing posterior (Retzius sparing) with anterior
      robot-assisted radical prostatectomy. MATERIALS AND METHODS: A total of 120
      patients with clinically low-intermediate risk prostate cancer were randomized to
      undergo robot-assisted radical prostatectomy via the posterior and anterior
      approach in 60 each. Surgery was performed by a single surgical team at an
      academic institution. An independent third party ascertained urinary and sexual
      function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic
      outcomes consisted of positive surgical margins and biochemical recurrence-free
      survival. Biochemical recurrence was defined as 2 postoperative prostate specific
      antigen values of 0.2 ng/ml or greater. RESULTS: Median age of the cohort was 61
      years and median followup was 12 months. At 12 months in the anterior vs
      posterior prostatectomy groups there were no statistically significant
      differences in the urinary continence rate (0 to 1 security pad per day in 93.3%
      vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection
      sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health
      Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs
      anterior prostatectomy groups a nonfocal positive surgical margin was found in
      11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93
      and postoperative complications developed in 18.3% vs 11.7%. CONCLUSIONS: Among
      patients with clinically low-intermediate risk prostate cancer randomized to
      anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical
      prostatectomy the differences in urinary continence seen at 3 months were muted
      at the 12-month followup. Sexual function recovery, postoperative complication
      and biochemical recurrence rates were comparable 1 year postoperatively.

PMID- 29225061
TI  - Crowdsourcing Disease Biomarker Discovery Research: The IP4IC Study.
AB  - PURPOSE: Biomarker discovery is limited by readily assessable, cost efficient
      human samples available in large numbers that represent the entire heterogeneity
      of the disease. We developed a novel, active participation crowdsourcing method
      to determine BP-RS (Bladder Permeability Defect Risk Score). It is based on
      noninvasive urinary cytokines to discriminate patients with interstitial
      cystitis/bladder pain syndrome who had Hunner lesions from controls and patients
      with interstitial cystitis/bladder pain syndrome but without Hunner lesions.
      MATERIALS AND METHODS: We performed a national crowdsourcing study in cooperation
      with the Interstitial Cystitis Association. Patients answered demographic,
      symptom severity and urinary frequency questionnaires on a HIPAA (Health
      Insurance Portability and Accountability Act) compliant website. Urine samples
      were collected at home, stabilized with a preservative and sent to Beaumont
      Hospital for analysis. The expression of 3 urinary cytokines was used in a
      machine learning algorithm to develop BP-RS. RESULTS: The IP4IC study collected a
      total of 448 urine samples, representing 153 patients (147 females and 6 males)
      with interstitial cystitis/bladder pain syndrome, of whom 54 (50 females and 4
      males) had Hunner lesions. A total of 159 female and 136 male controls also
      participated, who were age matched. A defined BP-RS was calculated to predict
      interstitial cystitis/bladder pain syndrome with Hunner lesions or a bladder
      permeability defect etiology with 89% validity. CONCLUSIONS: In this novel
      participation crowdsourcing study we obtained a large number of urine samples
      from 46 states, which were collected at home, shipped and stored at room
      temperature. Using a machine learning algorithm we developed BP-RS to quantify
      the risk of interstitial cystitis/bladder pain syndrome with Hunner lesions,
      which is indicative of a bladder permeability defect etiology. To our knowledge
      BP-RS is the first validated urine biomarker assay for interstitial
      cystitis/bladder pain syndrome and one of the first biomarker assays to be
      developed using crowdsourcing.

PMID- 29225062
TI  - Systematic review of the empirical investigation of resources to support decision
      making regarding BRCA1 and BRCA2 genetic testing in women with breast cancer.
AB  - OBJECTIVE: Identify existing resources developed and/or evaluated empirically in
      the published literature designed to support women with breast cancer making
      decisions regarding genetic testing for BRCA1/2 mutations. METHODS: Systematic
      review of seven electronic databases. Studies were included if they described or
      evaluated resources that were designed to support women with breast cancer in
      making a decision to have genetic counselling or testing for familial breast
      cancer. Outcome and process evaluations, using any type of study design, as well
      as articles reporting the development of decision aids, were eligible for
      inclusion. RESULTS: Total of 9 publications, describing 6 resources were
      identified. Resources were effective at increasing knowledge or understanding of
      hereditary breast cancer. Satisfaction with resources was high. There was no
      evidence that any resource increased distress, worry or decisional conflict. Few
      resources included active functionalities for example, values-based exercises, to
      support decision-making. CONCLUSION: Tailored resources supporting decision
      making may be helpful and valued by patients and increase knowledge of hereditary
      breast cancer, without causing additional distress. PRACTICE IMPLICATIONS:
      Clinicians should provide supportive written information to patients where it is
      available. However, there is a need for robustly developed decision tools to
      support decision-making around genetic testing in women with breast cancer.

PMID- 29225063
TI  - The infant motor system predicts actions based on visual statistical learning.
AB  - Motor theories of action prediction propose that our motor system combines prior
      knowledge with incoming sensory input to predict other people's actions. This
      prior knowledge can be acquired through observational experience, with
      statistical learning being one candidate mechanism. But can knowledge learned
      through observation alone transfer into predictions generated in the motor
      system? To examine this question, we first trained infants at home with videos of
      an unfamiliar action sequence featuring statistical regularities. At test, motor
      activity was measured using EEG and compared during perceptually identical time
      windows within the sequence that preceded actions which were either predictable
      (deterministic) or not predictable (random). Findings revealed increased motor
      activity preceding the deterministic but not the random actions, providing the
      first evidence that the infant motor system can use knowledge from statistical
      learning to predict upcoming actions. As such, these results support theories in
      which the motor system underlies action prediction.

PMID- 29225064
TI  - Intracranial high-gamma connectivity distinguishes wakefulness from sleep.
AB  - Neural synchrony in the gamma-band is considered a fundamental process in
      cortical computation and communication and it has also been proposed as a crucial
      correlate of consciousness. However, the latter claim remains inconclusive,
      mainly due to methodological limitations, such as the spectral constraints of
      scalp-level electroencephalographic recordings or volume-conduction confounds.
      Here, we circumvented these caveats by comparing gamma-band connectivity between
      two global states of consciousness via intracranial electroencephalography
      (iEEG), which provides the most reliable measurements of high-frequency activity
      in the human brain. Non-REM Sleep recordings were compared to passive-wakefulness
      recordings of the same duration in three subjects with surgically implanted
      electrodes. Signals were analyzed through the weighted Phase Lag Index
      connectivity measure and relevant graph theory metrics. We found that
      connectivity in the high-gamma range (90-120 Hz), as well as relevant graph
      theory properties, were higher during wakefulness than during sleep and
      discriminated between conditions better than any other canonical frequency band.
      Our results constitute the first report of iEEG differences between wakefulness
      and sleep in the high-gamma range at both local and distant sites, highlighting
      the utility of this technique in the search for the neural correlates of global
      states of consciousness.

PMID- 29225065
TI  - An unbiased data-driven age-related structural brain parcellation for the
      identification of intrinsic brain volume changes over the adult lifespan.
AB  - This study aims to elucidate age-related intrinsic brain volume changes over the
      adult lifespan using an unbiased data-driven structural brain parcellation.
      Anatomical brain images from a cohort of 293 healthy volunteers ranging in age
      from 21 to 86 years were analyzed using independent component analysis (ICA). ICA
      based parcellation identified 192 component images, of which 174 (90.6%) showed a
      significant negative correlation with age and with some components being more
      vulnerable to aging effects than others. Seven components demonstrated a convex
      slope with aging; 3 components had an inverted U-shaped trajectory, and 4 had a U
      shaped trajectory. Linear combination of 86 components provided reliable
      prediction of chronological age with a mean absolute prediction error of
      approximately 7.2 years. Structural co-variation analysis showed strong
      interhemispheric, short-distance positive correlations and long-distance, inter
      lobar negative correlations. Estimated network measures either exhibited a U- or
      an inverted U-shaped relationship with age, with the vertex occurring at
      approximately 45-50 years. Overall, these findings could contribute to our
      knowledge about healthy brain aging and could help provide a framework to
      distinguish the normal aging processes from that associated with age-related
      neurodegenerative diseases.

PMID- 29225066
TI  - Perturbation of whole-brain dynamics in silico reveals mechanistic differences
      between brain states.
AB  - Human neuroimaging research has revealed that wakefulness and sleep involve very
      different activity patterns. Yet, it is not clear why brain states differ in
      their dynamical complexity, e.g. in the level of integration and segregation
      across brain networks over time. Here, we investigate the mechanisms underlying
      the dynamical stability of brain states using a novel off-line in silico
      perturbation protocol. We first adjust a whole-brain computational model to the
      basal dynamics of wakefulness and deep sleep recorded with fMRI in two
      independent human fMRI datasets. Then, the models of sleep and awake brain states
      are perturbed using two distinct multifocal protocols either promoting or
      disrupting synchronization in randomly selected brain areas. Once perturbation is
      halted, we use a novel measure, the Perturbative Integration Latency Index
      (PILI), to evaluate the recovery back to baseline. We find a clear distinction
      between models, consistently showing larger PILI in wakefulness than in deep
      sleep, corroborating previous experimental findings. In the models, larger
      recoveries are associated to a critical slowing down induced by a shift in the
      model's operation point, indicating that the awake brain operates further from a
      stable equilibrium than deep sleep. This novel approach opens up for a new level
      of artificial perturbative studies unconstrained by ethical limitations allowing
      for a deeper investigation of the dynamical properties of different brain states.

PMID- 29225068
TI  - Lysophosphatidylcholine and its phosphorothioate analogues potentiate insulin
      secretion via GPR40 (FFAR1), GPR55 and GPR119 receptors in a different manner.
AB  - Lysophosphatidylcholine (LPC) is an endogenous ligand for GPR119 receptor,
      mediating glucose-stimulated insulin secretion (GSIS). We demonstrate that LPC
      facilitates GSIS in MIN6 pancreatic beta-cell line and murine islets of
      Langerhans by recognizing not only GPR119 but also GPR40 (free fatty acid
      receptor 1) and GPR55 activated by lysophosphatidylinositol. Natural LPCs are
      unstable when administered in vivo limiting their therapeutic value and
      therefore, we present phosphorothioate LPC analogues with increased stability.
      All the modified LPCs under study (12:0, 14:0, 16:0, 18:0, and 18:1)
      significantly enhanced GSIS. The 16:0 sulfur analogue was the most potent,
      evoking 2-fold accentuated GSIS compared to the native counterpart.
      Interestingly, LPC analogues evoked GPR40-, GPR55-and GPR119-dependent [Ca2+]i
      signaling, but did not stimulate cAMP accumulation as in the case of unmodified
      molecules. Thus, introduction of a phosphorothioate function not only increases
      LPC stability but also modulates affinity towards receptor targets and evokes
      different signaling pathways.

PMID- 29225067
TI  - The dynamics of native Atoh7 protein expression during mouse retinal
      histogenesis, revealed with a new antibody.
AB  - The Atoh7 transcription factor catalyzes the rate-limiting step in the
      specification of retinal ganglion cells (RGCs). As a tool to study vertebrate
      retinal development, we validate an antibody that recognizes human and mouse
      Atoh7 polypeptide, using informative knockout and transgenic mouse tissues and
      overexpression experiments. The transient features of Atoh7 protein expression
      during retinal neurogenesis match the expected pattern at the tissue and cellular
      level. Further, we compare endogenous Atoh7 to established RGC markers, reporter
      mouse lines and cell cycle markers, demonstrating the utility of the antibody to
      investigate molecular mechanisms of retinal histogenesis.

PMID- 29225069
TI  - Stimulation of B-Raf increases c-Jun and c-Fos expression and upregulates AP-1
      regulated gene transcription in insulinoma cells.
AB  - Stimulation of pancreatic beta-cells with glucose activates the protein kinases B
      Raf and extracellular signal-regulated protein kinase that participate in glucose
      sensing. Inhibition of both kinases results in impairment of glucose-regulated
      gene transcription. To analyze the signaling pathway controlled by B-Raf, we
      expressed a conditionally active form of B-Raf in INS-1 insulinoma cells. Here,
      we show that stimulation of B-Raf strongly activated the transcription factor AP
      1 which is accompanied by increased c-Jun and c-Fos promoter activities, an
      upregulation of c-Jun and c-Fos biosynthesis, and elevated transcriptional
      activation potentials of c-Jun and c-Fos. Mutational analysis identified the AP-1
      sites within the c-Jun promoter and the serum response element (SRE) within the c
      Fos promoter as the essential genetic elements connecting B-Raf stimulation with
      AP-1 activation. In line with this, the transcriptional activation potential of
      the SRE-binding protein Elk-1 was increased following B-Raf activation. The
      signal pathway from B-Raf to AP-1 required the activation of c-Jun. We identified
      the cyclin D1 gene as a delayed response gene for AP-1 following stimulation of B
      Raf in insulinoma cells. Moreover, MAP kinase phosphatase-1 and the
      Ca2+/calmodulin-dependent protein phosphatase calcineurin were identified to
      function as shut-off-devices for the signaling cascade connecting B-Raf
      stimulation with the activation of AP-1. The fact that stimulation with glucose,
      activation of L-type voltage-gated Ca2+ channels, and stimulation of B-Raf all
      trigger an activation of AP-1 indicates that AP-1 is a point of convergence of
      signaling pathways in beta-cell.

PMID- 29225070
TI  - Escherichia coli spontaneous community-acquired meningitis in adults: A case
      report and literature review.
AB  - Gram-negative bacillary meningitis occurring post-trauma and following
      neurosurgical procedures has been described widely. However, reports of
      spontaneous cases are sparse, particularly community-acquired cases. Spontaneous
      community-acquired Escherichia coli meningitis is a rare (although increasingly
      seen) and specific entity that is poorly reported in the literature. A review of
      the literature identified only 43 cases of community-acquired E. coli meningitis
      reported between 1946 and 2016. This article describes two new cases of
      spontaneous community-acquired E. coli meningitis encountered in Marseille,
      France, and presents the results of a literature review on spontaneous community
      acquired E. coli meningitis.

PMID- 29225071
TI  - Clinical characteristics of pulmonary Mycobacterium lentiflavum disease in adult
      patients.
AB  - BACKGROUND: Mycobacterium lentiflavum is a slow-growing non-tuberculous
      Mycobacterium that is often associated with an immunocompromised state and
      cervical lymphadenitis in young children. However, little is known about the
      clinical importance of pulmonary infection with M. lentiflavum in adults.
      METHODS: The medical records of all adults who met the diagnostic criteria of
      pulmonary M. lentiflavum disease at Keio University Hospital and Fukujuji
      Hospital from 2001 to 2015 were reviewed. In addition, the PubMed database was
      searched to identify further reported cases in non-HIV adults. RESULTS: Five
      cases of pulmonary M. lentiflavum disease were identified in the medical records
      search and 11 additional cases were identified in the literature review. Eleven
      of the total 16 cases were female, and 15 of 16 cases showed a
      nodular/bronchiectatic pattern on chest computed tomography imaging. No cases
      showed an aggressive clinical course of pulmonary M. lentiflavum disease,
      although one patient died of an exacerbation of underlying vasculitis and
      bacterial pneumonia. CONCLUSIONS: The clinical characteristics of pulmonary M.
      lentiflavum disease in adult patients were identified. This disease mainly
      affects females, displays a nodular/bronchiectatic pattern on chest computed
      tomography imaging, and does not demonstrate an aggressive clinical course.
      Further larger studies are needed to reveal detailed clinical features.

PMID- 29225072
TI  - Intraventricular neurocysticercosis with interventricular foramen and generalized
      ventriculitis.

PMID- 29225073
TI  - Corrigendum to "131I-labeled chitosan hydrogels for radioembolization: a
      preclinical study in small animals" [Nucl Med Biol 52 (2017) 16-23].

PMID- 29225074
TI  - The effect of fish gender on susceptibility to acute Streptococcus agalactiae
      infection in Javanese medaka Oryzias javanicus.
AB  - This study describes the susceptibility of different fish gender following acute
      Streptococcus agalactiae infection by using Javanese medaka Oryzias javanicus as
      test fish. The fish were grouped into four groups, which were: (1) all-male; (2)
      all-female; (3) mixed-gender (1 male: 1 female ratio); and (4) control non
      infected (1 male: 1 female ratio). The fish in group 1, 2 and 3 were
      intraperitoneally exposed to 5.4 * 108 CFU/ml of S. agalactiae, while for group
      4, the fish were exposed using sterile broth. The main clinical signs and
      histopathological changes of infected Javanese medaka were commonly observed in
      S. agalactiae infected fishes. However, no difference on clinical signs and
      histopathological changes of fish in group 1, 2 and 3 were noticed. The Javanese
      medaka mortality in group 1, 2 and 3 were observed from 4 h post infection (hpi)
      to 6 hpi, with the cumulative mortality from 3% to 30%. Then, the mortality
      increased at 12 hpi, with the range from 53% to 80%. However, 100% of the
      infected fish dead at 24 hpi. No clinical signs, histopathological changes and
      fish mortality recorded in group 4. Generally, the clinical signs, mortality
      patterns, cumulative mortality and histopathological changes of Javanese medaka
      infected by S. agalactiae did not show any difference between the all-male, all
      female and mixed-gender groups. This indicates that the susceptibility of fish to
      S. agalactiae infection is not influenced by their gender.

PMID- 29225075
TI  - Multivalent Interactions with Fbw7 and Pin1 Facilitate Recognition of c-Jun by
      the SCFFbw7 Ubiquitin Ligase.
AB  - Many regulatory proteins, including the transcription factor c-Jun, are highly
      enriched in disordered protein regions that govern growth, division, survival,
      differentiation, and response to signals. The stability of c-Jun is controlled by
      poorly understood regulatory interactions of its disordered region with both the
      E3 ubiquitin ligase SCFFbw7 and prolyl cis-trans isomerase Pin1. We use nuclear
      magnetic resonance and fluorescence studies of c-Jun to demonstrate that
      multisite c-Jun phosphorylation is required for high-affinity interaction with
      Fbw7. We show that the Pin1 WW and PPIase domains interact in a dynamic complex
      with multiply phosphorylated c-Jun. Importantly, Pin1 isomerizes a pSer-Pro
      peptide bond at the c-Jun N terminus that affects binding to Fbw7 and thus
      modulates the ubiquitin-mediated degradation of c-Jun. Our findings support the
      general principle that multiple weak binding motifs within disordered regions can
      synergize to yield high-affinity interactions and provide rapidly evolvable means
      to build and fine-tune regulatory events.

PMID- 29225076
TI  - Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective
      Antagonist EMPA.
AB  - Orexin peptides in the brain regulate physiological functions such as the sleep
      wake cycle, and are thus drug targets for the treatment of insomnia. Using serial
      femtosecond crystallography and multi-crystal data collection with a synchrotron
      light source, we determined structures of human orexin 2 receptor in complex with
      the subtype-selective antagonist EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)
      (toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) at 2.30-A and 1.96-A
      resolution. In comparison with the non-subtype-selective antagonist suvorexant,
      EMPA contacted fewer residues through hydrogen bonds at the orthosteric site,
      explaining the faster dissociation rate. Comparisons among these OX2R structures
      in complex with selective antagonists and previously determined OX1R/OX2R
      structures bound to non-selective antagonists revealed that the residue at
      positions 2.61 and 3.33 were critical for the antagonist selectivity in OX2R. The
      importance of these residues for binding selectivity to OX2R was also revealed by
      molecular dynamics simulation. These results should facilitate the development of
      antagonists for orexin receptors.

PMID- 29225077
TI  - Structural Insights into the pH-Dependent Conformational Change and Collagen
      Recognition of the Human Mannose Receptor.
AB  - Mannose receptor (MR, CD206) is an endocytic receptor on microphages and
      dendritic cells. It recognizes multiple ligands and plays important roles in
      regulating immune responses and maintaining glycoprotein homeostasis. However,
      the structure and functional mechanism of MR remain unclear. Here we determine
      the crystal structures of the N-terminal fragments of MR and reveal the potential
      binding mode of collagen on the fibronectin II domain. The SAXS and other
      biophysical data suggest that MR adopts an extended conformation at physiological
      pH and undergoes conformational changes as pH decreases, resulting in a compact
      conformation in an acidic environment. Moreover, biochemical data show that MR
      binds to collagen in a Ca2+-enhanced manner at physiological pH, whereas Ca2+ has
      no effect on the binding at acidic pH. These results provide a model for the
      dynamic mechanism of MR regarding its ligand binding and release during the
      recycling between cell surface and endosomes.

PMID- 29225079
TI  - Structural Basis for the Recruitment of Ctf18-RFC to the Replisome.
AB  - Ctf18-RFC is an alternative PCNA loader which plays important but poorly
      understood roles in multiple DNA replication-associated processes. To fulfill its
      specialist roles, the Ctf18-RFC clamp loader contains a unique module in which
      the Dcc1-Ctf8 complex is bound to the C terminus of Ctf18 (the Ctf18-1-8 module).
      Here, we report the structural and functional characterization of the
      heterotetrameric complex formed between Ctf18-1-8 and a 63 kDa fragment of DNA
      polymerase E. Our data reveal that Ctf18-1-8 binds stably to the polymerase and
      far from its other functional sites, suggesting that Ctf18-RFC could be
      associated with Pol E throughout normal replication as the leading strand clamp
      loader. We also show that Pol E and double-stranded DNA compete to bind the same
      winged-helix domain on Dcc1, with Pol E being the preferred binding partner, thus
      suggesting that there are two alternative pathways to recruit Ctf18-RFC to sites
      of replication.

PMID- 29225078
TI  - Regulation of Androgen Receptor Activity by Transient Interactions of Its
      Transactivation Domain with General Transcription Regulators.
AB  - The androgen receptor is a transcription factor that plays a key role in the
      development of prostate cancer, and its interactions with general transcription
      regulators are therefore of potential therapeutic interest. The mechanistic basis
      of these interactions is poorly understood due to the intrinsically disordered
      nature of the transactivation domain of the androgen receptor and the generally
      transient nature of the protein-protein interactions that trigger transcription.
      Here, we identify a motif of the transactivation domain that contributes to
      transcriptional activity by recruiting the C-terminal domain of subunit 1 of the
      general transcription regulator TFIIF. These findings provide molecular insights
      into the regulation of androgen receptor function and suggest strategies for
      treating castration-resistant prostate cancer.

PMID- 29225081
TI  - Enteral nutrition and quality of life in patients undergoing chemoradiotherapy
      for esophageal carcinoma: a comparison of nasogastric tube, esophageal stent, and
      ostomy tube feeding.
AB  - BACKGROUND AND AIMS: This study prospectively recruited esophageal squamous cell
      carcinoma patients who received esophageal stent, nasogastric tube (NGT), or
      jejunostomy/gastrostomy feeding to compare the changes in nutritional status and
      quality of life during chemoradiation therapy (CRT). METHODS: In total, 81
      patients were analyzed (stent, 7; surgical ostomy, 26; NGT, 19; oral intake, 29).
      An NGT was inserted when, despite medication, dysphagia or pain worsened with
      oral feeding during CRT. Serial body weight and daily narcotic demand were
      recorded. Changes in serum albumin level and quality of life were also assessed.
      In subgroup analysis comparing NGT and prophylactic surgical ostomy feeding, 5
      patients with total occlusion in the ostomy group were excluded. RESULTS:
      Patients in all groups had similar decreases in mean body weight with an overall
      change of -6.41% +/- 5.21% at the end of CRT. The stent group had significantly
      worse pain, decreased albumin (-1.03 +/- .9 mg/dL), and decreased quality of life
      across CRT compared with the other groups. In subgroup analysis the stent group
      had significantly higher weight loss, whereas the NGT group had higher narcotic
      demand and slightly worse quality of life. Two patients (7.7%) had ileus days
      after jejunostomy creation. Five patients (23.8%) among those received
      prophylactic ostomy creation and scarcely used it. CONCLUSIONS: These preliminary
      results raise concerns that use of esophageal stents may be less suitable in
      patients undergoing CRT. Tube feeding by means of transnasal or percutaneous
      routes appear to be comparably effective during CRT, but both have advantages and
      disadvantages. We suggest a careful endoscopic evaluation to select the
      population more appropriate for NGT feeding on an as-needed basis during CRT.

PMID- 29225080
TI  - Second-Shell Basic Residues Expand the Two-Metal-Ion Architecture of DNA and RNA
      Processing Enzymes.
AB  - Synthesis and scission of phosphodiester bonds in DNA and RNA regulate vital
      processes within the cell. Enzymes that catalyze these reactions operate mostly
      via the recognized two-metal-ion mechanism. Our analysis reveals that basic amino
      acids and monovalent cations occupy structurally conserved positions nearby the
      active site of many two-metal-ion enzymes for which high-resolution (<3 A)
      structures are known, including DNA and RNA polymerases, nucleases such as Cas9,
      and splicing ribozymes. Integrating multiple-sequence and structural alignments
      with molecular dynamics simulations, electrostatic potential maps, and mutational
      data, we found that these elements always interact with the substrates,
      suggesting that they may play an active role for catalysis, in addition to their
      electrostatic contribution. We discuss possible mechanistic implications of this
      expanded two-metal-ion architecture, including inferences on medium-resolution
      cryoelectron microscopy structures. Ultimately, our analysis may inspire future
      experiments and strategies for enzyme engineering or drug design to modulate
      nucleic acid processing.

PMID- 29225082
TI  - Comparison of EUS with MRCP in idiopathic acute pancreatitis: a systematic review
      and meta-analysis.
AB  - BACKGROUND AND AIMS: Idiopathic acute pancreatitis (IAP) poses a diagnostic
      challenge for gastroenterologists, because confirmation of the disease etiology
      has important implications for the selection of the best possible treatment and
      the prevention of possible recurrence or the development of chronic pancreatitis
      (CP). ERCP, EUS, and MRCP typically are used to diagnose IAP when conventional
      radiologic methods fail. However, their exact role in the diagnosis of IAP has
      not yet been determined. METHODS: We searched the PubMed, EMBASE, OVID, Cochrane
      Library (including CENTRAL), China National Knowledge Infrastructure (CNKI), and
      Wanfang databases from inception to April 2017. Studies involving the use of EUS
      and/or MRCP for the etiologic diagnosis of IAP were included. A meta-analysis was
      performed by using Review Manager Version 5.2 for comparative studies and R
      software 3.3.3 to determine diagnostic yield of the studies. RESULTS: Among the
      34 studies that met the inclusion criteria (n = 2338), 7 studies used a
      combination of EUS and MRCP and totaled 249 patients. The results comparing EUS
      with MRCP showed a diagnostic yield of 153 of the 239 patients (64%) in the EUS
      group, which was higher than the yield of 82 of 238 patients (34%) in the MRCP
      group (P < .001) in the 7 studies, and the diagnostic yield was 60% in the EUS
      group, 24% in the MRCP group, and 43% in the MRCP after secretin stimulation (S
      MRCP) group. In our subgroup analysis of CP and biliary disease, EUS was superior
      to MRCP (P < .001), but when comparing the efficacy of the modalities in the
      diagnosis of pancreatic divisum, S-MRCP was obviously superior to MRCP and EUS
      (12% vs 2% vs 2%). CONCLUSION: EUS and MRCP should both be used in the diagnostic
      work-up of IAP as complementary techniques. EUS had a higher diagnostic accuracy
      than MRCP (64% vs 34%) in the etiologic diagnosis of IAP and should be preferred
      for establishing a possible biliary disease and CP diagnosis, whereas S-MRCP was
      superior to EUS and MRCP in diagnosing a possible anatomic alteration in the
      biliopancreatic duct system, such as pancreatic divisum.

PMID- 29225083
TI  - Computer-aided diagnosis for identifying and delineating early gastric cancers in
      magnifying narrow-band imaging.
AB  - BACKGROUND AND AIMS: Magnifying narrow-band imaging (M-NBI) is important in the
      diagnosis of early gastric cancers (EGCs) but requires expertise to master. We
      developed a computer-aided diagnosis (CADx) system to assist endoscopists in
      identifying and delineating EGCs. METHODS: We retrospectively collected and
      randomly selected 66 EGC M-NBI images and 60 non-cancer M-NBI images into a
      training set and 61 EGC M-NBI images and 20 non-cancer M-NBI images into a test
      set. After preprocessing and partition, we determined 8 gray-level co-occurrence
      matrix (GLCM) features for each partitioned 40 * 40 pixel block and calculated a
      coefficient of variation of 8 GLCM feature vectors. We then trained a support
      vector machine (SVMLv1) based on variation vectors from the training set and
      examined in the test set. Furthermore, we collected 2 determined P and Q GLCM
      feature vectors from cancerous image blocks containing irregular microvessels
      from the training set, and we trained another SVM (SVMLv2) to delineate cancerous
      blocks, which were compared with expert-delineated areas for area concordance.
      RESULTS: The diagnostic performance revealed accuracy of 96.3%, precision
      (positive predictive value [PPV]) of 98.3%, recall (sensitivity) of 96.7%, and
      specificity of 95%, at a rate of 0.41 +/- 0.01 seconds per image. The performance
      of area concordance, on a block basis, demonstrated accuracy of 73.8% +/- 10.9%,
      precision (PPV) of 75.3% +/- 20.9%, recall (sensitivity) of 65.5% +/- 19.9%, and
      specificity of 80.8% +/- 17.1%, at a rate of 0.49 +/- 0.04 seconds per image.
      CONCLUSIONS: This pilot study demonstrates that our CADx system has great
      potential in real-time diagnosis and delineation of EGCs in M-NBI images.

PMID- 29225084
TI  - Autophagy deficiency in myeloid cells exacerbates eosinophilic inflammation in
      chronic rhinosinusitis.
AB  - BACKGROUND: Eosinophilic inflammation is a major pathologic feature of chronic
      rhinosinusitis (CRS) and is frequently associated with severe refractory disease.
      Prostaglandin (PG) D2 levels are increased in patients with CRS, and PGD2 is an
      important contributing factor to eosinophilic inflammation. Autophagy has a
      pleiotropic effect on immune responses and disease pathogenesis. Recent studies
      suggest the potential involvement of autophagy in patients with CRS and the PG
      pathway. OBJECTIVE: We sought to investigate whether altered function of
      autophagy is associated with eosinophilic inflammation and dysregulated
      production of PGD2 in patients with CRS. METHODS: We used myeloid cell-specific
      deletion of autophagy-related gene 7 (Atg7), which is vital for autophagy, and
      investigated the effects of impaired autophagy on eosinophilic inflammation in a
      murine model of eosinophilic chronic rhinosinusitis (ECRS). The effect of
      autophagy on PGD2 production and gene expression profiles associated with allergy
      and the PG pathway were assessed. RESULTS: We found that impaired autophagy in
      myeloid cells aggravated eosinophilia, epithelial hyperplasia, and mucosal
      thickening in mice with ECRS. This aggravation was associated with gene
      expression profiles that favor eosinophilic inflammation, TH2 response, mast cell
      infiltration, and PGD2 dysregulation. Supporting this, PGD2 production was also
      increased significantly by impaired autophagy. Among other myeloid cells,
      macrophages were associated with autophagy deficiency, leading to increased IL
      1beta levels. Macrophage depletion or blockade of IL-1 receptor led to
      alleviation of eosinophilic inflammation and sinonasal anatomic abnormalities
      associated with autophagy deficiency. CONCLUSION: Our results suggest that
      impaired autophagy in myeloid cells, particularly macrophages, has a causal role
      in eosinophilic inflammation and ECRS pathogenesis.

PMID- 29225085
TI  - Anticytokine autoantibodies in a patient with a heterozygous NFKB2 mutation.

PMID- 29225086
TI  - Circulating allergen-specific TH2 lymphocytes: CCR4+ rather than CLA+ is the
      predominant phenotype in peanut-allergic subjects.

PMID- 29225088
TI  - Risk Factors, Clinical Presentation, and Outcomes for Abdominal Wall
      Endometriosis.

PMID- 29225087
TI  - Activation of ACE2/angiotensin (1-7) attenuates pancreatic beta cell
      dedifferentiation in a high-fat-diet mouse model.
AB  - OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) has been identified in
      pancreatic islets and can preserve beta cells. In this study, we aimed to examine
      the possible role of ACE2 and its end product, angiotensin 1-7 (A1-7), in
      reducing beta cell dedifferentiation during metabolic stress. METHODS: First, a
      lineage-tracing experiment was performed to track beta cells in mice fed a high
      fat diet (HFD). Second, the ACE2/A1-7 axis was evaluated in the HFD mouse model.
      Intraperitoneal glucose tolerance tests (IPGTTs) and intraperitoneal insulin
      tolerance tests (IPITTs) were conducted. Phenotypic changes in beta cells were
      detected by immunohistochemistry and quantitative real-time PCR. Pancreatic
      sections were immunostained for vascular endothelial growth factor (VEGF) and
      inducible nitric oxide synthase (iNOS). Finally, the effects of the ACE2/A1-7
      axis were explored in isolated mouse islets exposed to different concentrations
      of glucose. Glucose-stimulated insulin release and levels of insulin mRNA and
      OCT4 mRNA were measured. RESULTS: Pancreatic beta cell dedifferentiation occurred
      both in vitro and in vivo in response to metabolic stress and was accompanied by
      ACE2 reduction. HFD-induced insulin resistance and glucose intolerance were
      exacerbated in ACE2-knockout (ACE2KO) mice but were alleviated by exogenous A1-7
      in C57BL/6J mice. Approximately 20% of beta cells were dedifferentiated in ACE2KO
      mice fed a standard rodent chow diet (SD). A higher percentage of
      dedifferentiated beta cells was detected in ACE2KO mice than in wild-type (WT)
      mice under HFD conditions. In contrast, the administration of A1-7 alleviated HFD
      induced beta cell dedifferentiation in C57BL/6J mice. Moreover, the exogenous
      injection of A1-7 improved microcirculation in islets and decreased the
      production of iNOS in islets of C57BL/6J mice fed an HFD. Additionally, ACE2 was
      found to be mainly expressed in alpha cells of mice, while Mas, the receptor of
      A1-7, was distributed in beta cells. CONCLUSIONS: Overall, this study is the
      first to demonstrate that the ACE2/A1-7/Mas axis may be one of the intra-islet
      paracrine mechanisms of communication between alpha and beta cells. Enhancing the
      ACE2/A1-7 axis exerts a protective effect by ameliorating beta cell
      dedifferentiation, and this effect might be partially mediated through
      improvements in islet microcirculation and suppression of islet iNOS.

PMID- 29225089
TI  - Author's Reply.

PMID- 29225090
TI  - Transcriptome analysis of Trichophyton mentagrophytes-induced rabbit (Oryctolagus
      cuniculus) dermatophytosis.

PMID- 29225091
TI  - Gene expression profiling of the TRIM protein family reveals potential biomarkers
      for indicating tuberculosis status.
AB  - Tripartite motif (TRIM) family proteins play important regulatory roles in innate
      immune responses, the dysregulation of which cause several infectious diseases.
      However, the role and function of TRIM family proteins during tuberculosis (TB)
      infection remains unclear. In this study, we employed real-time quantitative PCR
      to profile the transcript levels of 72 TRIM genes from a cohort of 5 active TB
      patients, 5 latent tuberculosis infection (LTBI) subjects, and 5 healthy controls
      (HCs) in an initial discovery phase. The notable TRIM genes were assessed by in
      vitro cell infection experiments and further validated in another independent
      cohort (36 active TB, 24 LTBI and 28 HCs). The receiver operating characteristic
      (ROC) was used to analyze the diagnostic power of these TRIM genes. Our results
      revealed that 20 TRIM genes were decreased in active TB compared to LTBI and HCs.
      In addition, TRIM4, 16, 27, 32, 35, 46, 47, 65 and 68 were further shown to be
      downregulated in Mycobacterium smegmatis-infected macrophages and were found to
      be closely correlated with infection time and initial bacteria loads.
      Furthermore, the ROC analyses showed that TRIM4, 27 and 65 all exhibited the
      highest areas under the curve (AUC) values of 1.00 in discriminating active TB
      from LTBI and HCs. Moreover, TRIM27 combined with TRIM32 for an improved AUC
      value of 0.81 in discriminating LTBI from HCs. These results suggest that TRIM
      gene dysregulation might be involved in the pathogenesis of TB and that these
      genes could serve as potential biomarkers for indicating TB status.

PMID- 29225092
TI  - Molecular and phenotypic characterization of Photobacterium damselae among some
      marine fishes in Lake Temsah.
AB  - Photobacterium damselae species are one of the most devastating bacterial
      pathogens in mariculture worldwide. Some species of Photobacterium are pathogenic
      for marine animals and human. They are the causative agents of photobacteriosis,
      formerly known as pasteurellosis. A total of (202) marine fishes of three
      different species were represented as: seabass (Dicentrarchus labrax), seabream
      (Sparus aurata) and gray mullet (Mugil capitus) randomly collected from Lake
      Temsah at Ismailia governorate along the parallel Pelagic road to the lake in the
      governorate from August 2015 to July 2016. The clinical picture and gross lesions
      of the diseased fishes were recorded. Isolation and identification of suspected
      bacteria using traditional and molecular methods. Samples from affected organs
      were collected for studying the histopathological alterations of these pathogens.
      Fifty one fishes were found to be infected with Photobacterium damselae subsp.
      Piscicida. Seabass (Dicentrarchus labrax) was the most infected fish species
      (23), followed by seabream (Sparus aurata) (18) finally gray mullet (Mugil
      capitus) was (10). 91fishes were found to be infected with P. damselae subsp.
      damselae, seabass (Dicentrarchus labrax) was the most infected fish sp. (36),
      followed by seabream (Sparus aurata) (32), then gray mullet (Mugil capitus) (23).
      The results indicated that, the total prevalence of P. damselae subsp. piscicida
      in all examined species (25.24%), the highest seasonal prevalence was recorded in
      summer season (37.09%) followed by autumn (26%) then spring (20.37%) and winter
      (11.11%). On the other hand, the total prevalence of P. damselae subsp. damselae
      in all examined species (45.04%), the highest seasonal prevalence was recorded in
      summer season (67.74%) followed by autumn (52%) then spring (29.62%) and winter
      (19.44%). Molecular diagnosis with conventional PCR used to confirm the
      traditional isolation was applied by using specific primers of two genes
      (polycapsular saccharide gene and urease C gene). The histopathological studies
      of naturally infected marine fishes showed severe inflammatory reactions in
      different organs with accumulation of melanomacrophages and necrosis. The results
      confirm that P. damselae subspecies damsalea is the most prevalent pathogen
      between marine fishes, and seabass (Dicentrarchus labrax) was the highly affected
      marine fishes in this study.

PMID- 29225093
TI  - Effects of the antidepressant mirtazapine and zinc on nicotinic acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) and zinc are associated with
      regulation of mood and related disorders. In addition, several antidepressants
      inhibit muscle and neuronal nAChRs and zinc potentiates inhibitory actions of
      them. Moreover, mirtazapine (a noradrenergic, serotonergic and histaminergic
      antidepressant) inhibits muscarinic AChRs and its effects on nAChRs are unknown.
      Therefore, we studied the modulation of muscle alpha1beta1gammad nAChRs expressed
      in oocytes and native alpha7-containing nAChRs in hippocampal interneurons by
      mirtazapine and/or zinc, using voltage-clamp techniques. The currents elicited by
      ACh in oocytes (at -60 mV) were similarly inhibited by mirtazapine in the absence
      and presence of 100 MUM zinc (IC50 ~15 MUM); however, the ACh-induced currents
      were stronger inhibited with 20 and 50 MUM mirtazapine in the presence of zinc.
      Furthermore, the potentiation of ACh-induced current by zinc in the presence of 5
      MUM mirtazapine was 1.48 +/- 0.06, and with 50 MUM mirtazapine zinc potentiation
      did not occur. Interestingly, in stratum radiatum interneurons (at -70 mV), 20
      MUM mirtazapine showed less inhibition of the current elicited by choline (Ch)
      than at 10 MUM (0.81 +/- 0.02 and 0.74 +/- 0.02 of the Ch-induced current,
      respectively). Finally, the inhibitory effects of mirtazapine depended on
      membrane potential: 0.81 +/- 0.02 and 0.56 +/- 0.05 of the control Ch-induced
      current at -70 and -20 mV, respectively. These results indicate that mirtazapine
      interacts with muscle and neuronal nAChRs, possibly into the ion channel; that
      zinc may increase the sensitivity of nAChRs to mirtazapine; and that mirtazapine
      decreases the sensitivity of nAChRs to zinc.

PMID- 29225094
TI  - The "sweet" effect: Comparative assessments of dietary sugars on cognitive
      performance.
AB  - In recent years there has been increasing interest in studying cognitive effects
      associated with sugar consumption. Neuro-cognitive research has confirmed that
      glucose, as a main energy substrate for the brain, can momentarily benefit
      cognitive performances, particularly for memory functioning. However, there is
      still limited understanding of relative effects of other common sugars (e.g.,
      fructose and sucrose) on cognitive performance. The present study tested in 49
      people the effects of three common dietary sugars against a placebo sweetener
      (i.e., sucralose), on performance of three well-studied cognitive tasks - simple
      response time, arithmetic, and Stroop interference, all of which are suggested to
      rely on the prefrontal lobe. A double-blind, placebo-controlled, cross-over
      experimental design was used. Results revealed that ingestion of glucose and
      sucrose led to poorer performances on the assessed tasks as opposed to fructose
      and the placebo (p<0.05); these effects were particularly pronounced under the
      fasting condition in comparison to the non-fasting condition (p<0.001). Overall,
      these results indicate that cognitive effects of sugar are unlikely to be
      mediated by the perception of sweetness. Rather, the effects are mediated by
      glucose. Further research should systematically assess effects of dietary sugars
      on other cognitive domains, such as memory, to give further insights on general
      cognitive effects of sugar consumption.

PMID- 29225095
TI  - Restriction of dietary protein leads to conditioned protein preference and
      elevated palatability of protein-containing food in rats.
AB  - The mechanisms by which intake of dietary protein is regulated are poorly
      understood despite their potential involvement in determining food choice and
      appetite. In particular, it is unclear whether protein deficiency results in a
      specific appetite for protein and whether influences on diet are immediate or
      develop over time. To determine the effects of protein restriction on
      consumption, preference, and palatability for protein we assessed patterns of
      intake for casein (protein) and maltodextrin (carbohydrate) solutions in adult
      rats. To induce a state of protein restriction, rats were maintained on a low
      protein diet (5% casein) and compared to control rats on non-restricted diet (20%
      casein). Under these dietary conditions, relative to control rats, protein
      restricted rats exhibited hyperphagia without weight gain. After two weeks, on
      alternate conditioning days, rats were given access to either isocaloric casein
      or maltodextrin solutions that were saccharin-sweetened and distinctly flavored
      whilst consumption and licking patterns were recorded. This allowed rats to learn
      about the post-ingestive nutritional consequences of the two different solutions.
      Subsequently, during a preference test when rats had access to both solutions, we
      found that protein-restricted rats exhibited a preference for casein over
      carbohydrate whereas non-restricted rats did not. Analysis of lick microstructure
      revealed that this preference was associated with an increase in cluster size and
      number, reflective of an increase in palatability. In conclusion, protein
      restriction induced a conditioned preference for protein, relative to
      carbohydrate, and this was associated with increased palatability.

PMID- 29225096
TI  - Triglycerides and glycated hemoglobin for screening insulin resistance in obese
      patients.
AB  - OBJECTIVE: Assessment of insulin resistance (IR) is essential in non-diabetic
      patients with obesity. Thus study aims to identify the best determinants of IR
      and to propose an original approach for routine assessment of IR in obesity.
      DESIGN AND PATIENTS: All adult with obesity defined by a body mass index
      >=30kg/m2, evaluated in the Nutrition Department between January 2010 and January
      2015 were included in this cross-sectional study. Patients with diabetes were
      excluded. IR was diagnosed according to the HOMA-IR. Based on a logistic
      regression, we determined a composite score of IR. We then tested the variables
      with a principal component analysis and a hierarchical clustering analysis.
      RESULTS: A total of 498 patients with obesity were included. IR was associated
      with grade III obesity (OR=2.6[1.6-4.4], p<0.001), HbA1c>=5.7% (OR=2.6[1.7-4.0],
      p<0.001), hypertriglyceridemia >1.7mmol/l (OR=3.0[2.0-4.5], p<0.001) and age
      (OR=0.98[0.96-0.99], p=0.002). Exploratory visual analysis using factor map and
      clustering analysis revealed that lipid and carbohydrates metabolism
      abnormalities were correlated with insulin resistance but not with excessive fat
      accumulation and low-grade inflammation. CONCLUSIONS: Our results highlight the
      interest of simple blood tests such as HbA1c and triglyceride determination,
      which associated with BMI, may be widely available tools for screening IR in
      obese patients.

PMID- 29225097
TI  - Vitrification of two active pharmaceutical ingredients by fast scanning
      calorimetry: From structural relaxation to nucleation phenomena.
AB  - Cinchonidine and Theophylline vitrification abilities have been investigated by
      differential and fast scanning calorimetry. These active pharmaceutical compounds
      are known in the literature to have a very high tendency to crystallize which has
      been confirmed by classical differential scanning calorimetry. Due to the growing
      interest in amorphous pharmaceutical compounds, their possible vitrifications
      have been investigated by fast scanning calorimetry. This work shows the high
      potential of this advanced thermal analysis technique to investigate the
      vitrification of active pharmaceutical compounds by melt-quenching protocol. For
      the first time, glass transitions of Cinchonidine and Theophylline were measured.
      From Cinchonidine, it has been shown that complete glassy state can be obtained
      by cooling from the melt at 2000K/s. Crystallization has also been suppressed by
      cooling down from the melt at 2K/s. However, such rate does not avoid the
      formation of nuclei. Theophylline crystallization process has been suppressed by
      a melt-quenching protocol carried out with a cooling rate of 4000K/s. However,
      the phenomenon of nuclei formation upon cooling seems unavoidable at this cooling
      rate. For both active pharmaceutical compounds, physical aging has been observed
      to play a role on the nuclei formation below the glass transition leading to
      modify the subsequent crystallization.

PMID- 29225098
TI  - Xanthan gum as a rate-controlling polymer for the development of alcohol
      resistant matrix tablets and mini-tablets.
AB  - The vulnerability of controlled release formulations when co-ingested with
      alcohol represents a current major concern of regulatory agencies. Dose dumping
      might occur when drugs and/or excipients exhibit higher solubility in ethanolic
      solutions compared to water. In this study, xanthan gum was chosen as rate
      controlling polymer for the development of alcohol resistant matrix formulations
      and theophylline as model drug. Two polymer particle sizes (75 and 180MUm) and
      concentrations (30 and 60% w/w) were used to assess their influence on the in
      vitro drug release from directly compressed tablets and mini-tablets, in 0% and
      40% ethanol for 2h (pH 1.2). For both, tablets and mini-tablets, by using 60%
      xanthan gum similar dissolution profiles in hydrous and hydroalcoholic media were
      obtained, independently of the polymer particle size. By decreasing the polymer
      concentration a risk of alcohol-induced dose dumping was recognised, however only
      when larger polymer particles were used. In particular, mini-tablets underwent
      disintegration and released the entire dose within 5min in alcohol. Nevertheless,
      finer polymer particles used at lower concentration led to the formation of a
      more coherent and less porous gel layer and alcohol resistance could be tailored
      in regard to both matrix tablets and mini-tablets.

PMID- 29225099
TI  - Point of use production of liposomal solubilised products.
AB  - With the progression towards personalised and age-appropriate medicines, the
      production of drug loaded liposomes at the point of care would be highly
      desirable. In particular, liposomal solubilisation agents that can be produced
      rapidly and easily would provide a new option in personalised medicines. Such a
      process could also be used as a rapid tool for the formulation and pre-clinical
      screening of low soluble drugs. Within this paper, we outline a novel easy-to-use
      production method for point of use production of liposome solubilised drugs. Our
      results demonstrate that pre-formed multilamellar liposomes, stored in a fresh or
      frozen format, can be bilayer loaded with low solubility drugs using a simple
      bath sonication process. Sonication is undertaken in a sealed vial allowing the
      contents to remain sterile. Liposomes around 100 nm were prepared and these
      liposomes were able to increase the amount of drug dissolved by up to 10 fold.
      These liposomal solubilisation agents were stable in terms of size and drug
      solubilisation for up to 8 days when stored in the fridge making them an easy to
      use and robust small-scale tool for drug solubilisation.

PMID- 29225101
TI  - A poor outcome after surgical aortic replacement.

PMID- 29225100
TI  - Controllable encapsulation of alpha-mangostin with quaternized beta-cyclodextrin
      grafted chitosan using high shear mixing.
AB  - In this study, the inclusion complex formation between alpha-mangostin and water
      soluble quaternized beta-CD grafted-chitosan (QCD-g-CS) was investigated.
      Inclusion complex formation with encapsulation efficiency (%EE) of 5, 15 and 75%
      can be varied using high speed homogenizer. Tuning %EE plays a role on
      physicochemical and biological properties of alpha-mangostin/QCD-g-CS complex.
      Molecular dynamics simulations indicate that alpha-mangostin is included within
      the hydrophobic beta-CD cavity and being absorbed on the QCD-g-CS surface, with
      these results being confirmed by Fourier transform infrared (FTIR) spectroscopy.
      Probing the release characteristics of the inclusion complex at various %EE (5%,
      15% and 75%) in simulated saliva (pH 6.8) demonstrated that alpha-mangostin
      release rates were dependent on % EE (order 5% > 15% > 75%). Additionally, higher
      antimicrobial and anti-inflammation activities were observed for the inclusion
      complex than those of free alpha-mangostin due to enhance the solubility of alpha
      mangostin through the inclusion complex with QCD-g-CS.

PMID- 29225102
TI  - Always look at the sinus rhythm electrocardiogram in patients with ventricular
      tachycardia.

PMID- 29225103
TI  - What happens to non-responders in cardiac resynchronization therapy?
AB  - INTRODUCTION AND OBJECTIVES: Left ventricular reverse remodeling (LVRR) is
      strongly related to the long-term prognosis of patients undergoing cardiac
      resynchronization therapy (CRT). The aim of this study was to assess the long
      term clinical outcome of patients without LVRR at six months after CRT
      implantation and to determine the prognostic impact of clinical response in this
      population. METHODS: We analyzed 178 consecutive patients who underwent
      successful CRT device implantation (age 64+/-11 years; 69% male; 89% in New York
      Heart Association [NYHA] functional class III; 35% with ischemic cardiomyopathy).
      Clinical status and echocardiographic parameters were determined before and six
      months after CRT implantation. We identified those without criteria for LVRR
      (>=10% increase in left ventricular ejection fraction with >=15% reduction in
      left ventricular end-systolic diameter compared to baseline). Clinical responders
      were defined by a sustained improvement of at least one NYHA functional class.
      RESULTS: At six-month assessment after CRT, 109 (61%) patients showed LVRR.
      During a mean follow-up of 56+/-21 months, 47 (26%) patients died, with higher
      mortality in the group without LVRR (36% vs. 20%, p=0.023). Clinical response was
      greater in patients with LVRR (88% vs. 55%, p<0.001). In patients without LVRR,
      clinical response to CRT was the strongest independent predictor of survival
      (hazard ratio: 0.120; 95% confidence interval: 0.039-0.366; p<0.001). CONCLUSION:
      Although patients without LVRR six months after CRT implantation had a worse
      prognosis, with higher all-cause mortality, clinical response can be an
      independent predictor of survival in this population.

PMID- 29225104
TI  - Evaluation of QT dispersion and T-peak to T-end interval in patients with early
      stage sarcoidosis.
AB  - INTRODUCTION AND AIM: Sarcoidosis increases inhomogeneity in ventricular
      repolarization due to the presence of sarcoid granuloma, which significantly
      correlates with ventricular fibrillation. Various studies have suggested that the
      interval from the peak to the end of the electrocardiographic T wave (T-peak to T
      end [Tpe] interval) may correspond to the transmural dispersion of repolarization
      and that increased Tpe interval and Tpe/QT ratio are associated with malignant
      ventricular arrhythmias. The present study hypothesized that QT and Tpe intervals
      are significantly prolonged in sarcoidosis patients without apparent cardiac
      involvement. METHODS: The study population consisted of 54 patients (37 female;
      mean age 43.4+/-10.6 years) under follow-up for sarcoidosis and 56 healthy
      subjects (37 female; mean age 42.4+/-8.6 years). RESULTS: There was no
      statistically significant difference between the groups in maximum QT interval,
      QT dispersion or corrected QT (QTc) interval, but QTc dispersion and Tpe interval
      were significantly prolonged in the sarcoidosis group compared to the control
      group (QTc dispersion 59.9+/-22.5 and 44.4+/-23.8, respectively, p=0.001; Tpe
      interval 79.4+/-9.3 and 70.7+/-7.03, respectively, p<0.001). We also found that
      the Tpe/QT ratio was significantly higher in sarcoidosis patients compared to the
      control group (0.21+/-0.02 and 0.18+/-0.23, respectively, p<0.001). CONCLUSION:
      Our study revealed that QTc dispersion, Tpe and Tpe/QT ratio were greater in
      sarcoidosis patients compared to the control group. To our knowledge, the present
      study is the first to use Tpe interval analysis in patients without cardiac
      involvement in sarcoidosis. Tpe interval and Tpe/QT ratio may be promising
      markers for cardiovascular morbidity and mortality due to ventricular arrhythmias
      in patients with and without cardiac involvement in sarcoidosis.

PMID- 29225105
TI  - Interpretation of B-type natriuretic peptides in the era of angiotensin receptor
      neprilysin inhibitors.
AB  - Assessment of serum levels of natriuretic peptides, especially the amino-terminal
      portion (NT-proBNP) and the carboxy-terminal portion (BNP) of pro-B-type
      natriuretic peptide, has had a highly significant clinical impact on the
      diagnosis and prognostic stratification of patients with heart failure (HF). They
      are now an instrument with recognized value in this context and several studies
      have demonstrated their value in tailoring therapy for these patients. Following
      the recent advent of angiotensin receptor-neprilysin inhibitors (ARNIs), there is
      a need to review how these two biomarkers are interpreted in HF. The use of ARNIs
      is associated with a reduction in NT-proBNP but an increase in BNP levels. The
      authors of this concise article review the interpretation of natriuretic peptide
      levels in the light of the most recent evidence.

PMID- 29225106
TI  - Tannic acid (TA): A molecular tool for chelating and imaging labile iron.
AB  - This report presents the potential utilization of tannic acid (TA) as a natural
      iron chelator. TA is capable of binding with small ferric complexes without
      competitive binding with endogenous iron-containing molecules such as ferritin
      and transferrin. It was observed that the extracellular iron binding of TA
      resulted in the formation of self-assembled Fe3+-TA complexes, which were then
      taken up by HepG2 cells via phagocytosis pathway with autophagy-inducing
      properties. Obviously, TA was found to inhibit iron-induced HepG2 cell growth.
      However, cellular interactions and biological responses to the treatment were
      found to depend on availability of iron. Based on the results of the iron efflux
      experiment, it can be stated that TA has the capability to mobilize iron from
      cells in the form of assembled Fe3+-TA complexes. Interestingly, TA-mediated
      cellular iron influx and efflux were successfully monitored via MRI. The results
      of this study suggest that TA can be used as a molecular tool for chelating and
      imaging labile iron. This might be a promising approach for prevention and
      treatment of iron-associated cancer or other iron overload disorders.

PMID- 29225107
TI  - Comparison of blood-brain barrier penetration efficiencies between linear and
      cyclic all-d-enantiomeric peptides developed for the treatment of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD), until now, is an incurable progressive
      neurodegenerative disease. To target toxic amyloid beta oligomers in AD patients'
      brains and to convert them into non-toxic aggregation-incompetent species, we
      designed peptides consisting solely of d-enantiomeric amino acid residues. The
      original lead compound was named D3 and several D3 derivatives were designed to
      enhance beneficial properties. Here, we compare four d-peptides concerning their
      efficiencies to pass the blood-brain barrier (BBB). We demonstrate that the d
      peptides' concentrations in murine brain directly correlate with concentrations
      in cerebrospinal fluid. The cyclic d-enantiomeric peptide cRD2D3 is characterized
      by the highest efficiency to pass the BBB. For in total three cyclic peptides we
      show that administration of cyclic peptides resulted in up to tenfold higher peak
      concentrations in brain as compared to their linear equivalents which have
      partially been characterized before (Jiang et al., 2015; Leithold et al., 2016a).
      These results suggest that cyclic peptides pass the murine BBB more efficiently
      than their linear equivalents. cRD2D3's proteolytic stability, oral
      bioavailability, long duration of action and its favorable brain/plasma ratio
      reveal that it may become a suitable drug for long-term AD-treatment from a
      pharmacokinetic point of view.

PMID- 29225108
TI  - K-space trajectories in 3D-GRASE sequence for high resolution structural imaging.
AB  - PURPOSE: To propose and evaluate new k-space trajectories for 3D-GRASE to improve
      scan time over 3D-FSE/TSE for high resolution structural imaging. METHODS: Five
      different Cartesian k-space trajectories were developed and evaluated. They
      combine ideas of existing k-space trajectories for 3D-GRASE and 3D-FSE/TSE. T2
      and T2* are linearly or radially modulated in k-space to achieve the desired
      contrast while including the autocalibration region needed for the parallel
      imaging reconstruction technique. Phase modulation among echoes was corrected in
      reconstruction to remove remaining artefacts. Simulation and in-vivo experiments
      on a 3T scanner were conducted to evaluate the performance of the different k
      space trajectories. RESULTS: Two of the proposed k-space trajectories for high
      resolution structural imaging with 3D-GRASE obtained images comparable to 3D-FSE
      with lower specific absorption rate (PD/T2: 41%/75%) and shorter acquisition time
      (PD/T2: 27%/20%). CONCLUSIONS: 3D-GRASE image quality strongly depends on the k
      space trajectory. With an optimal trajectory, 3D-GRASE may be preferable over 3D
      FSE/TSE for structural high-resolution MRI.

PMID- 29225109
TI  - Raspberry ketone protects against isoproterenol-induced myocardial infarction in
      rats.
AB  - AIM: The cardioprotective role of raspberry ketone (RK) against isoproterenol
      (ISO)-induced myocardial infarction (MI) in rats was assessed. MATERIALS AND
      METHODS: Rats were randomly divided into Group I - Vehicle control; Group II -
      Toxic control ISO (85mg/kg, s.c.); Group III, IV and V - RK (50, 100 and
      200mg/kg, respectively) with ISO; Group VI- RK (200mg/kg) alone; Group VII -
      Propranolol (10mg/kg) with ISO; and Group VIII - Propranolol (10mg/kg) alone.
      After twenty-four hours of the last dose, animals were sacrificed and creatine
      kinase-MB, lactate dehydrogenase, total cholesterol, triglycerides, high-density
      lipoprotein, low-density-lipoprotein, very-low-density-lipoprotein,
      malondialdehyde, reduced glutathione, superoxide dismutase, catalase, Na+, K+
      ATPase, nitric oxide, histopathological and immunohistochemical analysis (tumor
      necrosis factor-alpha and inducible nitric oxide synthase) were performed. KEY
      FINDINGS: Treatment with ISO significantly deviated the biochemical parameters
      from the normal levels, which were considerably restored by RK at 100 and
      200mg/kg doses. 50mg/kg dose, however, did not demonstrate any significant
      cardioprotective action. The histopathological and immunohistochemical analysis
      further substantiated these findings. SIGNIFICANCE: Our study showed a dose
      dependent reduction in oxidative stress, inflammation and dyslipidemia by RK in
      ISO-intoxicated rats, which signifies that RK from the European red raspberry
      plant might be a valuable entity for the management of MI.

PMID- 29225110
TI  - Assessment of the cerebellar neurotoxic effects of nicotine in prenatal alcohol
      exposure in rats.
AB  - The adverse effects of prenatal nicotine and alcohol exposure on human
      reproductive outcomes are a major scientific and public health concern. In the
      United States, substantial percentage of women (20-25%) of childbearing age
      currently smoke cigarettes and consume alcohol, and only a small percentage of
      these individuals quit after learning of their pregnancy. However, there are very
      few scientific reports on the effect of nicotine in prenatal alcohol exposure on
      the cerebellum of the offspring. Therefore, this study was conducted to
      investigate the cerebellar neurotoxic effects of nicotine in a rodent model of
      Fetal Alcohol Spectrum Disorder (FASD). In this study, we evaluated the
      behavioral changes, biochemical markers of oxidative stress and apoptosis,
      mitochondrial functions and the molecular mechanisms associated with nicotine in
      prenatal alcohol exposure on the cerebellum. Prenatal nicotine and alcohol
      exposure induced oxidative stress, did not affect the mitochondrial functions,
      increased the monoamine oxidase activity, increased caspase expression and
      decreased ILK, PSD-95 and GLUR1 expression without affecting the GSK-3beta. Thus,
      our current study of prenatal alcohol and nicotine exposure on cerebellar
      neurotoxicity may lead to new scientific perceptions and novel and suitable
      therapeutic actions in the future.

PMID- 29225111
TI  - Liraglutide regulates the viability of pancreatic alpha-cells and pancreatic beta
      cells through cAMP-PKA signal pathway.
AB  - AIMS: As a glucagon-like peptide-1 receptor agonist, liraglutide could
      effectively increase insulin secretion from pancreatic beta-cells and suppress
      glucagon secretion from pancreatic alpha-cells in the treatment of hyperglycemia
      in type 2 diabetes patients. However, the mechanisms for the different regulation
      of pancreatic alpha-cells and beta-cells are still unclear. In this study, we
      mainly explored the different effects of liraglutide on mouse pancreatic alpha
      cell line and beta-cell line in vitro. MAIN METHODS: Herein, mouse pancreatic
      alpha-cell line, alpha-TC1-6, and mouse pancreatic beta-cell line, beta-TC-tet,
      were used to analyze the biological effects of liraglutide in different
      concentrations. Cell proliferation, cell apoptosis and cell secretion ability
      were detected in different groups. Besides, the level of miR-375 and cAMP-PKA
      signal pathway were further evaluated using qPCR and western blot. KEY FINDINGS:
      The results indicated that liraglutide could increase the level of miR-375 and
      cell apoptosis in pancreatic alpha-cells through inhibiting the cAMP-PKA signal
      pathway, but activate cAMP-PKA signal pathway in pancreatic beta-cells, and
      further lead to the down-regulation of miR-375 and improve cell viability.
      Therefore, the treatment with liraglutide could down-regulate the glucagon
      secretion ability of alpha-TC1-6 cells, and the insulin secretion ability of beta
      TC-tet cells was enhanced with the liraglutide treatment in a dose-dependent
      manner. SIGNIFICANCE: In conclusion, we mainly found that liraglutide could
      regulate the viability of pancreatic alpha-cells and pancreatic beta-cells
      through inhibiting and activating cAMP-PKA signal pathway respectively. The
      better understanding of the mechanism could help us to develop more novel therapy
      methods for diabetes in the future.

PMID- 29225113
TI  - Experimental periodontitis in rats potentiates inflammation at a distant site:
      Role of B1 kinin receptor.

PMID- 29225112
TI  - Fisetin: A bioactive phytochemical with potential for cancer prevention and
      pharmacotherapy.
AB  - A wide variety of chronic diseases, such as neurodegenerative and cardiovascular
      disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are
      now being treated with cost effective phytomedicines. Since synthetic medicines
      are very expensive, concerted efforts are being made in developing and poor
      countries to discover cost effective medicines for the treatment of non
      communicable diseases (NCDs). Understanding the underlying mechanisms of
      bioactive medicines from natural sources would not only open incipient avenues
      for the scientific community and pharmaceutical industry to discover new drug
      molecules for the therapy of NCDs, but also help to garner knowledge for
      alternative therapeutic approaches for the management of chronic diseases.
      Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the
      bioactive phytochemicals that have potential to block multiple signaling pathways
      associated with NCDs such as cell division, angiogenesis, metastasis, oxidative
      stress, and inflammation. The emerging evidence suggests that fisetin may be
      useful for the prevention and management of several types of human malignancies.
      Efforts are being made to enhance the bioavailability of fisetin after oral
      administration to prevent and/or treat cancer of the liver, breast, ovary and
      other organs. The intent of this review is to highlight the in vitro and in vivo
      activities of fisetin and to provide up-to-date information about the molecular
      interactions of fisetin with its cellular targets involved in cancer initiation,
      promotion and progression as well as to focus on strategies underway to increase
      the bioavailability and reduce the risk of deleterious effects, if any,
      associated with fisetin administration.

PMID- 29225115
TI  - Thoracic disc herniation: Surgical treatment.
AB  - Thoracic disc herniation is rare and mainly occurs between T8 and L1. The
      herniation is calcified in 40% of cases and is labeled as giant when it occupies
      more than 40% of the spinal canal. A surgical procedure is indicated when the
      patient has severe back pain, stubborn intercostal neuralgia or neurological
      deficits. Selection of the surgical approach is essential. Mid-line calcified
      hernias are approached from a transthoracic incision, while lateralized soft
      hernias can be approached from a posterolateral incision. The complication rate
      for transthoracic approaches is higher than that of posterolateral approaches;
      however, the former are performed in more complex herniation cases. The
      thoracoscopic approach is less invasive but has a lengthy learning curve.
      Retropleural mini-thoracotomy is a potential compromise solution. Fusion is
      recommended in cases of multilevel herniation, herniation in the context of
      Scheuermann's disease, when more than 50% bone is resected from the vertebral
      body, in patients with preoperative back pain or herniation at the thoracolumbar
      junction. Along with complications specific to the surgical approach, the
      surgical risks are neurological worsening, dural breach and subarachnoid-pleural
      fistulas. Giant calcified herniated discs are the largest contributor to
      myelopathy, intradural extension and postoperative complications. Some of the
      technical means that can be used to prevent complications are explored, along
      with how to address these complications.

PMID- 29225114
TI  - Fructose-induced inflammation and increased cortisol: A new mechanism for how
      sugar induces visceral adiposity.
AB  - Traditionally, the leading hypothesis regarding the development of obesity
      involves caloric imbalance, whereby the amount of calories consumed exceeds the
      amount of calories burned which causes obesity. Another hypothesis for why we get
      fat has surfaced in the last decade which is the idea that the overconsumption of
      added sugars and refined carbohydrates induce insulin resistance and high insulin
      levels causing obesity. While insulin is a fat-storing hormone, this hypothesis
      does not explain visceral adiposity, or why certain people are found to have fat
      stored in and around their organs. We propose a new mechanism for body fattening,
      particular visceral adiposity. This hypothesis involves the overconsumption of
      fructose, which leads to inflammation in all cells that metabolize it rapidly.
      When fructose is metabolized in subcutaneous adipocytes, the subsequent
      inflammation leads to an increase in intracellular cortisol in order to help
      squelch the inflammation. Unfortunately, the increase in intracellular cortisol
      leads to an increased flux of fatty acids out of the subcutaneous adipocytes
      allowing more substrate for fat storage into visceral fat tissue. Moreover
      fructose-induced inflammation in the liver also leads to increased intracellular
      cortisol via an upregulation of 11-B hydroxysteroid dehydrogenase type 1 causing
      increased fat storage in the liver (i.e., fatty liver). In essence, the fructose
      induced inflammatory cortisol response causes "thin on the outside, fat on the
      inside" (TOFI). Furthermore, fructose in the brain, either from fructose uptake
      via the blood brain barrier or endogenous formation from glucose via the polyol
      pathway stimulates an increased release of cortisol causing hepatic
      gluconeogenesis leading to overall insulin resistance and further body fattening.
      This review paper will discuss in detail the hypothesis that fructose-induced
      inflammation and cortisol activation causes visceral adiposity.

PMID- 29225116
TI  - HLA-A, -B, -C and -DRB1 allele and haplotype frequencies in the Macedonian
      population based on a family study.
AB  - AIM: The aim of this study was to determine HLA allele and 2-, 3- and 4-loci
      haplotype frequencies in a sample from Macedonian population with defined
      haplotypes based on family history. MATERIAL AND METHODS: We analysed 286
      unrelated individuals with Macedonian origin, parents of patients who needed stem
      cell transplantation, in the period of 01.01.2003 till 31.12.2016. Allele and
      haplotype frequencies, as well as Hardy-Weinberg equilibrium were calculated
      using the Arlequin3.5 software. Population comparison was calculated using the
      PHYLIP software. RESULTS: We identified 18 HLA-A, 26 HLA-B, 13 HLA-C and 13 HLA
      DRB1 allele group families. The most frequent allele groups in our population
      were HLA-A*02 (29.0%), HLA-A*24 (13.8%), HLA-B*35 (16.1%), HLA-B*51 (14.7%), HLA
      B*18 (14.7%), HLA-C*07 (27.9%), HLA-DRB1*11 (25.5%) and HLA-DRB1*16 (14.8%). The
      most frequent four loci haplotype was HLA-A*01-B*08-C*07-DRB1*03 (2.7%). Our
      comparison showed that the Macedonian population is closely related to the
      neighbouring countries in the Balkan Peninsula. CONCLUSION: This study provides
      data about the HLA diversity in the Macedonian population, which can be very
      important in the process of unrelated donor search, and in addition yields
      control group for future disease association studies in our population.

PMID- 29225117
TI  - Rapid Response Events in Hospitalized Patients: Patient Symptoms and Clinician
      Communication.
AB  - CONTEXT: Patients triggering rapid response team (RRT) intervention are at high
      risk for adverse outcomes. Data on symptom burden of these patients do not
      currently exist, and current symptom management and communication practices of
      RRT clinicians are unknown. OBJECTIVES: We sought to identify the symptom
      experience of RRT patients and observe how RRT clinicians communicate with
      patients and their families. METHODS: We conducted a prospective observational
      study from August to December 2015. Investigators attending RRT events measured
      frequencies of symptom assessment, communication, and supportive behaviors by RRT
      clinicians. As the rapid response event concluded, investigators measured patient
      reported pain, dyspnea, and anxiety using a numeric rating scale of 0 (none) to
      10 (most severe), with uncontrolled symptoms defined as numeric rating scale
      score of >=4. RESULTS: We observed a total of 52 RRT events. RRT clinicians
      assessed for pain during the event in 62% of alert patients, dyspnea in 38%, and
      anxiety in 21%. Goals of care were discussed during 3% of events and within 24
      hours in 13%. For the primary outcome measure, at the RRT event conclusion, 44%
      of alert patients had uncontrolled pain, 39% had uncontrolled dyspnea, and 35%
      had uncontrolled anxiety. CONCLUSION: Hospitalized patients triggering RRT events
      have a high degree of uncontrolled symptoms that are infrequently assessed and
      treated. Although these patients experience an acute change in medical status and
      are at high risk for adverse outcomes, goals-of-care discussions with RRT
      patients or families are rarely documented in the period after the events.

PMID- 29225118
TI  - Cardioprotective effect of Asphodelus tenuifolius Cav. on blood pressure and
      metabolic alterations in glucose-induced metabolic syndrome rats-An
      ethnopharmacological approach.

PMID- 29225119
TI  - D-chiro-inositol enriched Fagopyrum tataricum (L.) Gaench extract alleviates
      mitochondrial malfunction and inhibits ER stress/JNK associated inflammation in
      the endothelium.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tartary buckwheat is a food medicine dual-use
      crop with healing effects on cardiovascular diseases and type2 diabetes. It has
      been proposed that endothelial dysfunction is the initial lesion in these
      diseases and it's associated with mitochondrial dysfunction, endoplasmic
      reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive
      compound of Tartary buckwheat and is always deficit in type2 diabetes. However,
      it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate
      mitochondrial dysfunction, ER stress and inflammation in the endothelium.
      MATERIAL AND METHODS: Endothelial cells were treated with palmitic acid (PA) and
      mice were fed with high fat diet (HFD). The effects of DCI-enriched Tartary
      buckwheat bran extract (TBBE) on superoxide anion generation, dynamin-related
      protein 1 (Drp1), mitofusin2 (Mfn2), inositol-requiring enzyme-1alpha (IRE1alpha)
      and Jun n-terminal kinase (JNK) activation and inflammation in the endothelium
      against lipotoxicity were investigated. RESULTS: In endothelial cells, TBBE
      significantly inhibited oxidative stress. Meanwhile, in HFD-fed mice and PA
      induced cells, TBBE regulated Drp1 phosphorylation and inhibited its activation,
      implying the protective effect of TBBE on mitochondrial morphology. As a result,
      TBBE protected mitochondrial function. Additionally, TBBE inhibited ER stress and
      reduced the production of IL-6 and VCAM-1, associated with JNK pathway, thereby
      inhibiting the caspase-3 activation in vivo and in vitro. CONCLUSIONS: Taken
      together, this study indicated the beneficial role of TBBE in endothelial
      inflammation, with emphasis on mitochondrial dysfunction, ER stress and JNK
      activation.

PMID- 29225120
TI  - Retained Bullet in the Kidney: Imaging and Conservative Management.
AB  - Renal gunshot wounds resulting in a grade IV injury (AAST) should be explored
      only if they involve the hilum or if there are signs of suspected renal pelvis or
      ureteral laceration, active hemorrhage, peritonitis, or hemodynamically unstable
      patients (Kitrey et al, 2017).1 However, because of the paucity of cases reported
      in the literature, it is not clear what the best management of patients with a
      retained bullet is, which have been traditionally treated with surgical retrieval
      in other organs. We present the radiological findings and a clinical case summary
      of a patient with grade IV kidney injury and retained bullet managed
      conservatively.

PMID- 29225121
TI  - Anatomical Control of Adenoma Technique: An Accurate Surgical Approach to Thulium
      Laser Enucleation of the Prostate.
AB  - OBJECTIVE: To present our 2-lobe technique of thulium laser transurethral
      enucleation of the prostate. Transurethral resection of prostate and open
      prostatectomy have been traditionally considered as the gold standard for benign
      prostatic enlargement surgical treatment. Laser has been recently made available
      for benign prostatic enlargement surgery to minimize morbidity of traditional
      surgery.1 In 2009, Bach et al introduced the use of thulium laser,2 describing
      the 3-lobe technique, which overlaps open prostatectomy but with a greater
      control of hemostasis.3 Two techniques have been recently published that differ
      from the original one.4,5 Kim et al described the "All-in-One" technique,4
      whereas Wolters et al described a 2-lobe enucleation (left lobe first, then
      combined enucleation of the right and median lobe).5 We developed a different en
      block enucleation technique. METHODS: In our 2-lobe enucleation technique, the
      median lobe is enucleated first, whereas the lateral lobes are dissected and
      enucleated en bloc. Once the medial lobe is moved into the bladder lumen, the
      dissection is carried out at 4-o'clock position toward the bladder neck,
      enucleating the left lobe in an anticlockwise direction. At 12-o'clock position,
      dissection keeps going beneath the right lobe toward the 9-o'clock position. At
      this point, an incision is made at 8-o'clock position and enucleation is
      completed in a clockwise direction toward the 9-o'clock position. The 2
      enucleated tissues are finally morcellated. RESULTS: Preoperative prostate volume
      was 55 cc. Operative time was 36 minutes. The decrease in hemoglobin was 1.1 g/dL
      24 hours after surgery. Catheter was removed in first postoperative day and the
      patient was discharged home. Removed tissue weighed 45 g and showed <5% Gleason
      score 3 + 3 adenocarcinoma. CONCLUSION: Our enucleation technique may offer
      perioperative outcomes comparable with other approaches in medium-sized prostates
      (up to 100 mL), and we believe that is helpful in following correctly the
      surgical capsule plane. This technique speeds up the procedure and helps to leave
      no tissue behind.

PMID- 29225122
TI  - Dual Pathology Causing Congenital Bladder Outlet Obstruction.
AB  - Anterior urethral syringocele is an uncommon congenital deformity characterised
      by cystic dilatation of bulbo-urethral gland ducts and is usually asymptomatic.
      We present a case on 4-day-old male neonate who presented with bilateral
      antenatal hydroureteronephrosis and renal impairment and found to have urethral
      syringocele and posterior urethral valves (PUV).

PMID- 29225123
TI  - Clinical Utility and Biologic Implications of Phosphatase and Tensin Homolog
      (PTEN) and ETS-related Gene (ERG) in Prostate Cancer.
AB  - Phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) mutations are
      commonly found in prostate cancer. Although mouse studies have demonstrated that
      PTEN and ERG cooperatively interact during tumorigenesis, human studies examining
      these genes have been inconclusive. A systematic PubMed search including original
      articles assessing the pathogenesis of PTEN and ERG in prostate cancer was
      performed. Studies examining ERG's prognostic significance have conflicting
      results. Studies examining PTEN and ERG simultaneously found these genes are
      likely to occur together, but cooperative tumorigenesis functions have not been
      conclusively established. PTEN mutations are associated with a range of
      prognostic features. However, the practical clinical utility of this information
      remains to be determined.

PMID- 29225124
TI  - Time delays in the diagnosis and treatment of malaria in non-endemic countries: A
      systematic review.
AB  - BACKGROUND: Delays in diagnosis and treatment for malaria are associated with an
      increased risk for severe disease and mortality. Identifying the extent of
      patient and health system delay can provide a benchmark against which
      interventions to reduce delays can be measured. METHODS: We performed an
      electronic search in PubMed, EMBASE, Web of Science and LILACS for studies
      reporting time to diagnosis and treatment after return from travel, onset of
      symptoms and seeking healthcare in non-endemic countries. Additionally, theses,
      conference proceedings and nationally reported surveillance data were also
      searched for information on time delays. There were no language restrictions and
      all the studies were assessed for methodological quality. RESULTS: Data from 69
      papers out of 1719 identified records published between 2005 and 2017 were
      extracted; our findings show that median diagnosis delays of four or more days
      are common and patient delays accounted for a large proportion of diagnostic
      delay. There were limited data available on medical diagnostic delay. CONCLUSION:
      Patient delays accounted for a large proportion of the overall diagnostic delay;
      however the retrospective nature of the studies could have overestimated patient
      delay since previous healthcare contacts were not included. Additionally, the
      high frequency of studies reporting a clinically significant delay is a major
      concern.

PMID- 29225125
TI  - Interdependence of GLO I and PKM2 in the Metabolic shift to escape apoptosis in
      GLO I-dependent cancer cells.
AB  - Many cancer cells undergo metabolic reprogramming known as the Warburg effect,
      which is characterized by a greater dependence on glycolysis for ATP generation,
      even under normoxic conditions. Glyoxalase I (GLO I) is a rate-limiting enzyme
      involved in the detoxification of cytotoxic methylglyoxal formed in glycolysis
      and which is known to be highly expressed in many cancer cells. Thus, specific
      inhibitors of GLO I are expected to be effective anticancer drugs. We previously
      discovered a novel GLO I inhibitor named TLSC702. Although the strong inhibitory
      activity of TLSC702 was observed in the in vitro enzyme assay, higher
      concentrations were required to induce apoptosis at the cellular level. One of
      the proposed reasons for this difference is that cancer cells alter the energy
      metabolism leading them to become more dependent on mitochondrial respiration
      than glycolysis (Metabolic shift) to avoid apoptosis induction. Thus, we assumed
      that combination of TLSC702 with shikonin-a specific inhibitor of pyruvate kinase
      M2 (PKM2) that acts as a driver of TCA cycle by supplying pyruvate and which is
      known to be specifically expressed in cancer cells-would have anticancer effects.
      We herein show the anticancer effects of combination treatment with TLSC702 and
      shikonin, and a possible anticancer mechanism.

PMID- 29225126
TI  - Mutational analysis and dynamic simulation of S-limonene synthase reveal the
      importance of Y573: Insight into the cyclization mechanism in monoterpene
      synthases.
AB  - Monoterpene synthases carry out complex reactions to produce multiple products
      from a sole substrate, geranyl pyrophosphate (GPP). S-limonene synthase (LS) is a
      model monoterpene synthase that can be explored to understand the catalytic
      mechanism of these enzymes. In this study, we have identified an active site
      tyrosine residue (Y573) is crucial for the enzyme activity and mutational
      analysis indicates that both the aromatic ring and hydroxyl group are essential
      for the catalysis. Dynamic simulations found a hydrogen bond between Y573 and
      D496 and also a significant conformational change in the helical form of the LPP
      intermediate. Further mutagenesis suggested that this hydrogen bond is essential
      for catalysis. Sequence analysis suggested Y573 is completely conserved among
      cyclic monoterpene synthases but variable in acyclic enzymes, indicating this
      residue may be involved in cyclization. Subsequent studies by using neryl
      diphosphate (NPP) as the substrate ruled out the possibility that Y573 functions
      solely at the substrate isomerization step. Therefore, a more complicated role
      may be played by this residue. We proposed that Y573 may be involved in the
      earlier steps of the reaction, probably by controlling the conformation of the
      helical LPP intermediate. Our study provides important insights not only on the
      catalytic mechanism of LS, but also on the cyclization of monoterpene synthases
      in general.

PMID- 29225127
TI  - Simultaneous Endovascular Repair of a Thoracic Aortic Injury during Posterior
      Pedicle Screw Removal: A Case Report.
AB  - Posterior spinal stabilization is a technically demanding procedure which is
      increasing in popularity. Since this increase in popularity, complications,
      including screws misplacement, are being highlighted. Accuracy rates are higher
      when imaging modalities are used intraoperatively. Vascular injuries following
      posterior spinal stabilization are rare and are usually discovered late on
      subsequent imaging. Immediate perioperative compromise is rare, but nonetheless,
      resultant vascular injuries can be life threatening. A 72-year-old woman had a
      posterior spinal stabilization for severe pain caused by discitis. Routine
      computed tomography scan, 2 weeks postoperatively, detected an incidental
      thoracic aortic injury due to a misplaced pedicle screw. Given the rarity of this
      complication, there is no guideline for the management of resultant aortic
      injuries. Options described in the literature include thoracotomy with open
      vascular repair and newer endovascular techniques. We describe a novel method of
      simultaneous endovascular repair of a thoracic aortic injury during posterior
      pedicle screw removal with the patient in the right decubitus position. Surgeons
      operating near high-risk vascular structures should use intraoperative imaging
      modalities to guide screw placement and reduce subsequent complication rates.
      During endovascular repair of resultant aortic injuries, several factors must be
      considered. In particular, the challenge of turning a patient with open groin
      access and an endovascular stent in place. This must be carried out with extreme
      care to avoid the following risks: loss of access, damage to the access vessels
      and bleeding, displacement of the stent or deployment wires, and loss of the
      sterile field.

PMID- 29225128
TI  - Aortic Anatomy and Complications of the Proximal Sealing Zone after Endovascular
      Treatment of the Thoracic Aorta.
AB  - BACKGROUND: Technical and clinical success of thoracic aortic endovascular
      procedures relies mainly on the choice of the proximal sealing zone (PSZ). The
      latter can be affected by multiple complications, all of them having a potential
      gravity and a direct link with the quality of the PSZ. The objective of this
      study was to analyze the risk factors of PSZ complications occurrence. METHODS:
      Between 2007 and 2015, all the patients treated by a thoracic stent graft in
      zones 2, 3, or 4 were retrospectively reviewed, with analysis of the preoperative
      and postoperative angio-computed tomography. Proximal sealing zone complications
      are type Ia endoleaks, bird beak >=20 mm, malposition >=11 mm, migration >=10 mm,
      and retrograde dissection. Three types of potential risk factors were analyzed:
      (1) related to the patients (age, gender, pathology, urgency, hybrid surgery);
      (2) related to the stent graft (bare or covered proximal stent, degree of
      oversizing, number of stents, generation); (3) related to the morphology (radius
      of curvature, diameter, degree of conicity, calcifications and thrombus of the
      neck, depth of the arch, angulation of the proximal sealing zone, and tortuosity
      index of the arch and the thoracic aorta. RESULTS: Seventy-six patients (mean
      age: 54 years, 17-93 years) were treated for traumatic aortic rupture (n = 27,
      35.5%), aortic dissection (n = 26, 34%), aneurysm (n = 15, 20%), and other
      diseases (floating thrombus, aortoesophageal fistula) (n = 8, 10.5%). A hybrid
      surgery was carried out in 18 patients (24%). Primary technical success was 93.5%
      (n = 71). With a mean follow-up of 29 months, 30 PSZ complications were observed
      in 21 patients (28%): type Ia endoleaks (n = 3, 4%), bird beak (n = 7, 9%),
      malposition (n = 3, 4%), migration (n = 1, 1.5%), retrograde dissection (n = 1,
      1.5%), or several complications (n = 6, 7.8%). Among the morphological factors, 2
      parameters were significantly associated with the occurrence of complications:
      tortuosity index (group without PSZ complications 1.62 +/- 0.2 vs. group with PSZ
      complications 1.72 +/- 0.2, P = 0.042), and the diameter of the proximal neck
      (group without PSZ complications 25.7 +/- 5 vs. group with PSZ complications 31
      +/- 6.0, P = 0.001). Neither the demographic factors nor those related to the
      stent graft presented a statistically significant relation with the occurrence of
      complications. CONCLUSIONS: This work clearly highlights the relation between PSZ
      complications, independently of their type, and the local and global aortic
      morphology. A wide proximal neck, > 34 mm, and an important aortic tortuosity, >
      1.8, are situations at risk.

PMID- 29225129
TI  - Hydrogen sulfide as a regulatory factor in kidney health and disease.
AB  - Hydrogen sulfide (H2S) is synthesized in nearly all organ systems including the
      kidney. Recent findings have revealed that H2S functions as a gasotransmitter
      affecting a wide range of physiologic functions similar to other gasotransmitters
      nitric oxide (NO) and carbon monoxide (CO). Research on H2S regulation of kidney
      function is still in early stages. H2S increases glomerular filtration rate (GFR)
      and inhibits sodium absorption by the tubules. There is burgeoning evidence that
      H2S generation by kidney cells is reduced in acute and chronic disease states and
      that H2S donors ameliorate injury. However, there are hints that the gas could
      also mediate kidney injury in specific models suggesting that its participation
      in kidney pathology is context-dependent. Expanding investigation of H2S in
      kidney physiology and disease will not only help us understand its regulatory
      role but it may also give us a potential new target for therapeutic intervention.

PMID- 29225131
TI  - Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and
      HBV infections.
AB  - Tenofovir (TFV) is the cornerstone of the treatment and prophylaxis of HIV
      infections. It has been routinely used in its prodrug form TDF (tenofovir
      disoproxil fumarate) combined with emtricitabine ((-)FTC) and other
      antiretroviral agents. TDF has now been replaced by TAF (tenofovir alafenamide)
      which allows better uptake by the lymphoid tissue. In combination with
      elvitegravir (E), cobicistat (C), emtricitabine (F), TAF can be advocated as an
      STR (single tablet regimen, Genvoya(r)) for the treatment of HIV infections. In
      this combination, E and C may in the future be replaced by bictegravir. The
      prophylaxis of HIV infection is momentarily based upon Truvada(r), the
      combination of F with TDF, which in the future may also be replaced by TAF. TAF
      (Vemlidy(r)) has also replaced TDF (Viread(r)) for the treatment of hepatitis B
      virus (HBV) infections. Both TDF and TAF offer little or no risk for virus-drug
      resistance. As compared to TDF, TAF limits the risk for nephrotoxicity and loss
      of bone mineral density. What remains to be settled, however, before the
      universal use of TAF could be recommended, is its safety during pregnancy and its
      applicability in the treatment of tuberculosis, in combination with rifampicin.

PMID- 29225130
TI  - On the G protein-coupling selectivity of the native A2B adenosine receptor.
AB  - A2B adenosine receptor (A2BAR) activation induces Gs-dependent cyclic AMP
      accumulation. However, A2BAR G protein-coupling to other signaling events, e.g.
      ERK1/2 and calcium, is not well documented. We explored Gi, Gq/11 and Gs coupling
      in 1321 N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously
      expressing human A2BAR, using NECA or nonnucleoside BAY60-6583 as agonist,
      selective Gi, Gs and Gq/11 blockers, and CRISPR/Cas9-based Gq- and Gs-null HEK293
      cells. In HEK293 cells, A2BAR-mediated ERK1/2 activity occurred via both Gi and
      Gs, but not Gq/11. However, HEK293 cell calcium mobilization was completely
      blocked by Gq/11 inhibitor UBO-QIC and by Gq/11 knockout. In T24 cells, Gi was
      solely responsible for A2BAR-mediated ERK1/2 stimulation, and Gs suppressed
      ERK1/2 activity. A2BAR-mediated intracellular calcium mobilization in T24 cells
      was mainly via Gi, although Gs may also play a role, but Gq/11 is not involved.
      In 1321 N1 astrocytoma cells A2BAR activation suppressed rather than stimulated
      ERK1/2 activity. The ERK1/2 activity decrease was reversed by Gs downregulation
      using cholera toxin, but potentiated by Gi inhibitor pertussis toxin, and UBO-QIC
      had no effect. EPACs played an important role in A2BAR-mediated ERK1/2 signaling
      in all three cells. Thus, A2BAR may: couple to the same downstream pathway via
      different G proteins in different cell types; activate different downstream
      events via different G proteins in the same cell type; activate Gi and Gs, which
      have opposing or synergistic roles in different cell types/signaling pathways.
      The findings, relevant to drug discovery, address some reported controversial
      roles of A2BAR and could apply to signaling mechanisms in other GPCRs.

PMID- 29225132
TI  - Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of
      the ROS/JNK/p53 pathway in colorectal cancer cells.
AB  - The use of ginsenosides in cancer therapy has been intensively investigated. The
      ginsenoside Rh4 (Rh4), a rare saponin obtained from Panax notoginseng, dissolves
      in water more readily than total saponins, making this compound easier to use in
      anti-cancer pharmaceutics. Here, we investigated the antiproliferative activity
      and mechanisms of Rh4 in colorectal cancer, both in vivo and in vitro. A
      colorectal cancer xenograft model showed that Rh4 significantly inhibited tumor
      growth with few side effects. CCK-8 assays, flow cytometric analysis, Western
      blotting and immunohistochemistry revealed that Rh4 effectively suppressed
      colorectal cancer cell proliferation via inducing G0/G1 phase arrest, caspase
      dependent apoptosis and autophagic cell death but was not significantly cytotoxic
      to normal colon epithelial cells. Furthermore, apoptosis played a dominant role
      in Rh4-induced cell death, as the pan-caspase inhibitor Z-VAD-FMK blocked cell
      death to a greater extent than the autophagy inhibitor 3-methyladenine. Moreover,
      Rh4 increased reactive oxygen species (ROS) accumulation and subsequently
      activated the JNK-p53 pathway. An ROS scavenger and JNK and p53 inhibitors
      significantly attenuated Rh4-induced apoptosis and autophagy. Thus, the present
      study is the first to illustrate that Rh4 triggers apoptosis and autophagy via
      activating the ROS/JNK/p53 pathway in colorectal cancer cells, providing basic
      scientific evidence that Rh4 shows great potential as an anti-cancer agent.

PMID- 29225133
TI  - Medicaid in Transition: Proposed Changes in Funding Mechanisms and Their
      Consequences.

PMID- 29225134
TI  - Severe Facial Fracture is Related to Severe Traumatic Brain Injury.
AB  - BACKGROUND: Facial fractures frequently occur with traumatic brain injury (TBI).
      The relationship between facial fractures and brain trauma remains controversial.
      The objective of this study was to analyze the correlation between facial
      fracture and TBI. METHODS: Clinical and radiologic data of a total of 206
      patients were retrospectively collected from May 2011 to December 2015 in a
      single institute. Facial fracture was classified by the Facial Injury Severity
      Scale (FISS). TBI was grouped according to the Glasgow Coma Scale. Outcome was
      measured with the Glasgow Outcome Scale Extended 3, 6, and 12 months after
      trauma. RESULTS: There were 206 TBI patients with concomitant facial fracture
      including 166 (78.1%) males and 40 (19.4%) females. Mean age of all patients was
      46 +/- 19 years. Contusion and brain swelling were more frequent in higher FISS
      patients. Cranial surgery was done in 63 cases while facial fracture surgery was
      performed in 89 cases. There were 33 expired cases, including 6 cases due to
      multi-organ failure. High FISS was significantly associated with severe TBI and
      less favorable outcome 3 months after trauma. Concomitant surgical treatment for
      TBI and facial fracture was done in 21 cases without achieving more improved
      outcome compared with staged operations for 41 cases. CONCLUSION: Severity of
      facial fracture might be correlated with severity of TBI. Surgical timing of
      facial fracture with TBI patients does not affect the outcome of TBI.

PMID- 29225135
TI  - Adult Spinal Ependymomas: An Epidemiologic Study.
AB  - OBJECTIVE: In adults, spinal ependymomas constitute only 3% to 6% of central
      nervous system tumors. Because of their rarity and poor prognosis, large
      population-based studies are needed to assess the epidemiology and survival risk
      factors associated with these tumors in the hope of improving outcome. The
      authors undertook this retrospective study to explore factors that may influence
      survival in adult patients with spinal ependymomas. METHODS: Using the
      Surveillance, Epidemiology, and End Results database, a prospective cancer
      registry, the authors retrospectively assessed survival in histologically
      confirmed spinal ependymomas in patients 18 years of age and older. Survival was
      described with Kaplan-Meier curves, and a multivariate regression analysis was
      used to assess the association of several variables with survival while
      controlling for confounding variables. RESULTS: Overall survival at 1 year, 3
      years, and 5 years after diagnosis was 97.0%, 94.3%, and 93.3%, respectively.
      Patient age at diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI]
      1.04-1.07, P < 0.001), tumor grade IV (HR 11.11, 95% CI 1.27-97.02, P = 0.032),
      and the use of radiation therapy during the course of treatment (HR 4.42, 95% CI
      1.69-11.57, P = 0.003) were each associated with decreased survival. Gross total
      resection (HR 0.42, 95% CI 0.20-1.10, P = 0.026) was associated with improved
      overall survival. Gender, tumor size, and tumor extension were not found to
      impact survival. CONCLUSIONS: High-grade ependymomas occurring in the spine have
      a much worse prognosis than do those with lower grades. Early diagnosis and
      surgery appear to be associated with improved survival and outcomes, whereas
      radiation therapy has an unclear role.

PMID- 29225136
TI  - In vitro apoptotic mechanism of a novel synthetic Quinazolinyl derivative:
      Induces caspase-dependent intrinsic pathway on THP-1, leukemia cell line.
AB  - Several quinazoline derivatives have been found to possess a broad spectrum of
      biological activities. Previously our research group has synthesized and studied
      the anti-proliferative effects of N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine
      (DMQA). The current study evaluated the cytotoxic and apoptotic properties of
      DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay
      on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A
      549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's).
      Preliminary data revealed that the highest cytotoxic activity was against THP-1
      leukemia cell line (IC50=0.66 MUg/ml). The apoptotic properties of DMQA on THP-1
      cells were characterized by change in nuclear morphology, DNA fragmentation,
      reduction of pro-caspases-3, 9, Bax/Bcl-2 levels, cleavage of poly (ADP-ribose)
      polymerase and cytosolic release of cytochrome c. Further investigation revealed
      a sub-G1 peak, phosphatidyl serine exposure and loss of mitochondrial membrane
      potential (MMP) in THP-1 cells. The role of caspases was crucial and was
      demonstrated by the inhibitors Z-VAD-FMK and Z-DEVD-FMK. Moreover DMQA was
      markedly less effective in inhibiting the growth of normal cells (PBMC's, IC50
      =62.17 MUg/ml). Based on the results we suggest that DMQA induced apoptosis via
      intrinsic pathway and could be a promising anticancer agent.

PMID- 29225138
TI  - 9-Hydroxycanthin-6-one isolated from stem bark of Ailanthus altissima induces
      ovarian cancer cell apoptosis and inhibits the activation of tumor-associated
      macrophages.
AB  - The stem bark of Ailanthus altissima is used in traditional medicine in Asia to
      treat a variety of diseases, including cancer. The aim of this study was to
      identify compounds with tumoricidal activity from A. altissima stem bark and to
      investigate their mechanisms of action. Among the 13 compounds isolated from the
      ethyl acetate fraction of A. altissima stem bark, the beta-carboline alkaloid 9
      hydroxycanthin-6-one had potent cytotoxicity in all three ovarian cancer cell
      types examined. 9-Hydroxycanthin-6-one induced apoptosis through the activation
      of caspases-3, -8, and -9. 9-Hydroxycanthin-6-one increased the intracellular
      levels of reactive oxygen species (ROS), and pre-treatment with the antioxidant N
      acetyl-l-cysteine (NAC) attenuated the pro-apoptotic activity of 9-hydroxycanthin
      6-one. Additionally, 9-hydroxycanthin-6-one was found to decrease the expressions
      of MCP-1 and RANTES, major determinants of macrophage recruitment at tumor sites,
      in ovarian cancer cells. Treatment with 9-hydroxycanthin-6-one inhibited the
      levels of M2 phenotype markers and some cancer-promoting factors, such as MMP-2,
      MMP-9, and VEGF, in macrophages educated in ovarian cancer conditioned medium.
      Taken together, these data suggest that 9-hydroxycanthin-6-one isolated from A.
      altissima stem bark induces apoptosis in human ovarian cancer cells through the
      caspase- and ROS-dependent pathways and inhibits the activation of tumor
      associated macrophages.

PMID- 29225137
TI  - Valproic acid, a histone deacetylase inhibitor, induces apoptosis in breast
      cancer stem cells.
AB  - Cancer stem-like cells (CSCs) are a cell subpopulation that can reinitiate
      tumors, resist chemotherapy, give rise to metastases and lead to disease relapse
      because of an acquired resistance to apoptosis. Especially, epigenetic
      alterations play a crucial role in the regulation of stemness and also have been
      implicated in the development of drug resistance. Hence, in the present study, we
      examined the cytotoxic and apoptotic activity of valproic acid (VPA) as an
      inhibitor of histone deacetylases (HDACs) against breast CSCs (BCSCs). Increased
      expression of stemness markers were determined by western blotting in
      mammospheres (MCF-7s, a cancer stem cell-enriched population) propagated from
      parental MCF-7 cells. Anti-growth activity of VPA was determined via ATP
      viability assay. The sphere formation assay (SFA) was performed to assess the
      inhibitory effect of VPA on the self-renewal capacity of MCF-7s cells.
      Acetylation of histon H3 was detected with ELISA assay. Cell death mode was
      performed by Hoechst dye 33342 and propidium iodide-based flouresent stainings
      (for pyknosis and membrane integrity), by M30 and M65 ELISA assays (for apoptosis
      and primary or secondary necrosis) as well as cytofluorimetric analysis (caspase
      3/7 activity and annexin-V-FITC staining for early and late stage apoptosis). VPA
      exhibited anti-growth effect against both MCF-7 and MCF-7s cells in a dose (0.6
      20 mM) and time (24, 48, 72 h) dependent manner. As expected, MCF-7s cells were
      found more resistant to VPA than MCF-7 cells. It was observed that VPA prevented
      mammosphere formation at relatively lower doses (2.5 and 5 mM) while the
      acetylation of histon H3 was increased. At the same doses, VPA increased the M30
      levels, annexin-V-FITC positivity and caspase 3/7 activation, implying the
      induction of apoptosis. The secondary necrosis (late stage of apoptosis) was also
      evidenced by nuclear pyknosis with propidium iodide staining positivity. Taken
      together, inhibition of HDACs is cytotoxic to BCSCs by apoptosis. Our results
      suggested that targeting the epigenetic regulation of histones may be a novel
      approach and hold significant promise for successful treatment of breast cancer.

PMID- 29225139
TI  - Astrocytes and ischemic tolerance.
AB  - A mild non-lethal ischemic episode can induce resistance to a subsequent severe
      ischemic injury in the brain. This phenomenon is termed ischemic tolerance or
      ischemic preconditioning, and is an endogenous mechanism that can provide robust
      neuroprotection. Because of its neuroprotective effects against cerebral ischemia
      or stroke, ischemic tolerance has been widely studied. However, almost all
      studies have been performed from the viewpoint of neurons. Accumulating evidence
      suggests that glial cells have various roles in regulation of brain function,
      including modulation of synaptic transmission, neuronal excitation, and neuronal
      structure. In addition, astrocytes are closely related to homeostasis, stability
      of brain function, and protection of neurons. However, glial cells have received
      only limited attention with regard to ischemic tolerance. Cross-ischemic
      preconditioning is a phenomenon whereby non-ischemic preconditioning such as
      mechanical, thermal, and chemical treatment can induce ischemic tolerance. Of
      these, chemical treatments that affect the immune system can strongly induce
      ischemic tolerance, suggesting that glial cells may have important roles in this
      process. Indeed, we and others have demonstrated that glial cells, especially
      astrocytes, play a pivotal role in the induction of ischemic tolerance. This
      glial-mediated ischemic tolerance provides a robust and long-lasting
      neuroprotection against ischemic injury. In this review, we discuss the
      mechanisms underlying glial-mediated ischemic tolerance, as well as its potential
      benefits, problems, and therapeutic application.

PMID- 29225140
TI  - Reactive astrocytes in Alzheimer's disease: A double-edged sword.
AB  - Alzheimer's disease (AD) is a chronic and fatal disease, in which neuronal damage
      at its late stage cannot be easily reversed. Because AD progression is caused by
      multiple factors including diverse cellular processes, studies on AD pathogenesis
      at the molecular and cellular level are challenging. Based on the lessons from
      unsuccessful neuron-focused research for an AD cure, non-cell autonomous
      mechanisms including brain inflammation and reactive astrocytes have recently
      been in the spotlight as potential therapeutic targets for AD. Studies have shown
      that reactive astrocytes are not only the result of inflammatory defense
      reactions, but also an active catabolic decomposer that acts by taking up amyloid
      beta toxins. Here, we give an overview of the characteristics of reactive
      astrocytes as pathological features of AD. Reactive astrocytes exert biphasic
      effects, that is, beneficial or detrimental depending on multiple factors. Many
      efforts have been put forth for defining and characterizing molecular signatures
      for the beneficial and detrimental reactive astrocytes. In the foreseeable
      future, manipulating and targeting each established molecular signature should
      have profound therapeutic implications for the treatment of AD.

PMID- 29225141
TI  - Effects of healthcare professional delivered early feeding interventions on
      feeding practices and dietary intake: A systematic review.
AB  - BACKGROUND: Childhood obesity is a global public health challenge. Parental
      feeding practices, such as responsive feeding, are implicated in the etiology of
      childhood obesity. PURPOSE: This systematic review aimed to examine of effects of
      healthcare professional-delivered early feeding interventions, on parental
      feeding practices, dietary intake, and weight outcomes for children up to 2
      years. The role of responsive feeding interventions was also specifically
      examined. METHODS: Databases searched included: CINAHL, the Cochrane Library,
      EMBASE, Medline, PubMed, PsycINFO, and Maternity and Infant Care. INCLUSION
      CRITERIA: participants are parents of children <=2 years; intervention includes
      focus on early child feeding to prevent overweight and obesity; intervention
      delivered by healthcare professionals. RESULTS: Sixteen papers, representing 10
      trials, met inclusion criteria for review. Six interventions included responsive
      feeding components. Interventions demonstrated inconsistent effects on feeding
      practices, dietary intake, and weight outcomes. Findings suggest some reductions
      in pressure to eat and infant consumption of non-core beverages. Responsive
      feeding based interventions demonstrate greater improvements in feeding
      approaches, and weight outcomes. CONCLUSIONS: The findings of this review
      highlight the importance of incorporating responsive feeding in healthcare
      professional delivered early feeding interventions to prevent childhood obesity.
      Observed inconsistencies across trials may be explained by methodological
      limitations.

PMID- 29225142
TI  - Ethical concerns regarding animal use mediate the relationship between variety of
      pets owned in childhood and vegetarianism in adulthood.
AB  - Plant-based and vegetarian diets have been shown to have diverse health and
      environmental benefits and also serve to reduce farmed animal exploitation. It is
      therefore worthwhile to gain a better understanding of the factors that play a
      role in the decision to refrain from animal products. Past studies have shown
      that childhood pet ownership predicts the likelihood of adherence to a vegetarian
      diet in adulthood. Building on this research, we tested the hypothesis that the
      number of different types of pets owned in childhood is positively associated
      with degree of restriction of animal products in adulthood, and that this
      relationship is mediated by pro-animal attitudes. A self-selected convenience
      sample of 325 participants (77.2% female; mean age = 30.23 +/- 12.5) reported on
      their vegetarian status and completed the Animal Advocacy Scale and Child Pet
      Ownership Questionnaire. The number of different pets owned in childhood was
      positively correlated with degree of vegetarianism in adulthood (p < 0.001), but
      was no longer a significant predictor when controlling for moral opposition to
      animal exploitation. A significant Sobel test (z = 4.36; p < 0.001) confirmed the
      presence of full mediation. Findings support the hypothesis that individuals who
      owned a greater variety of pets in childhood endorse more concerns regarding
      animal use. This, in turn, appears to predict the decision to refrain from animal
      products in adulthood. The possibility that an enhanced ability to generalize
      empathy from companion to laboratory, farm, and wildlife animals underlies this
      relationship should be examined in future research.

PMID- 29225143
TI  - Valproic acid disrupts the biomechanics of late spinal neural tube closure in
      mouse embryos.
AB  - Failure of neural tube closure in the early embryo causes neural tube defects
      including spina bifida. Spina bifida lesions predominate in the distal spine,
      particularly after exposure to the anticonvulsant valproic acid (VPA). How VPA
      specifically disturbs late stages of neural tube closure is unclear, as
      neurulation is usually viewed as a uniform 'zippering' process along the spine.
      We recently identified a novel closure site ("Closure 5") which forms at the
      caudal extremity of the mouse posterior neuropore (PNP) when completion of
      closure is imminent. Here we investigated whether distal spina bifida in VPA
      exposed embryos involves disruption of Closure 5. Exposure of E8.5 mouse embryos
      to VPA in whole embryo culture had marked embryotoxic effects, whereas toxic
      effects were less pronounced in more developmentally advanced (E9) embryos. Only
      33% of embryos exposed to VPA from E9 to E10.5 achieved PNP closure
      (control=90%). Short-term (8h) VPA treatment diminished supra-cellular F-actin
      cables which normally run along the lateral neural folds, and prevented caudal
      PNP narrowing normally characteristic of Closure 5 formation. Laser ablation of
      Closure 5 caused rapid neuropore widening. Equivalent ablations of the caudal PNP
      in VPA treated embryos resulted in significantly less widening, suggesting VPA
      prevents formation of Closure 5 as a biomechanically active structure. Thus, VPA
      exposure prevents morphological and biomechanical conversion of the caudal
      extreme of the PNP during late spinal closure. Closure 5 facilitates neural fold
      apposition when completion of closure is imminent, such that its disruption in
      VPA-exposed embryos may lead to distal spina bifida.

PMID- 29225144
TI  - Copy number variants in people with autism spectrum disorders and co-morbid
      psychosis.
AB  - The genetic association between autism spectrum disorder (ASD) and psychotic
      disorders such as schizophrenia is complicated and mirrors the clinical overlap
      between these conditions to some degree. However, no studies to date have
      examined the genetics of individuals dually diagnosed with both ASD and
      psychosis. In this study, we present findings of copy number variants (CNVs) from
      a study of 116 well-characterised individuals with this dual diagnosis. DNA was
      extracted and arrayed using the Affymetrix CytoScan HD 2.8M array or the
      Affymetrix Cytogenetics arrays and compared with existing samples from the
      Database of Genomic Variants and the Simons Simplex Collection of CNVs from
      individuals with ASD and their families. Twenty-seven novel CNVs >=20k base pairs
      were identified in the sample, most occurring in only a single individual,
      although two were found in two female participants. Forty-nine rare CNVs (<1.5%
      rate in general population) were also found at significantly higher frequencies
      than expected. The findings may provide evidence for areas of further study in
      the understanding of the development of both ASD and psychosis due to the number
      of affected genetic regions that have not previously been linked to these
      conditions.

PMID- 29225145
TI  - Surprisingly good outcome in antenatal diagnosis of severe hydrocephalus related
      to CCDC88C deficiency.
AB  - Non-syndromic congenital hydrocephalus is aetiologically diverse and while a
      genetic cause is frequently suspected, it often cannot be confirmed. The most
      common genetic cause is L1CAM-related X-linked hydrocephalus and that explains
      only 5%-10% of all male cases. This underlines a current limitation in our
      understanding of the genetic burden of non-syndromic congenital hydrocephalus,
      especially for those cases with likely autosomal recessive inheritance.
      Additionally, the prognosis for most cases of severe congenital hydrocephalus is
      poor, with most of the surviving infants displaying significant intellectual
      impairment despite surgical intervention. It is for this reason that couples with
      an antenatal diagnosis of severe hydrocephalus are given the option, and may opt,
      for termination of the pregnancy. We present two families with CCDC88C-related
      recessive congenital hydrocephalus with children who had severe hydrocephalus.
      Those individuals who were shunted within the first few weeks of life, who did
      not require multiple surgical revisions, and who had a more distal truncating
      variant of the CCDC88C gene met their early childhood developmental milestones in
      some cases. This suggests that children with CCDC88C-related autosomal recessive
      hydrocephalus can have normal developmental outcomes under certain circumstances.
      We recommend CCDC88C analysis in cases of severe non-syndromic congenital
      hydrocephalus, especially when aqueduct stenosis with or without a medial
      diverticulum is seen, in order to aid prognosis discussion.

PMID- 29225147
TI  - Host specificity in the Giardia duodenalis species complex.
AB  - Giardia duodenalis is a unicellular flagellated parasite that infects the
      gastrointestinal tract of a wide range of mammalian species, including humans.
      Investigations of protein and DNA polymorphisms revealed that G. duodenalis
      should be considered as a species complex, whose members, despite being
      morphologically indistinguishable, can be classified into eight groups, or
      Assemblages, separated by large genetic distances. Assemblages display various
      degree of host specificity, with Assemblages A and B occurring in humans and many
      other hosts, Assemblage C and D in canids, Assemblage E in hoofed animals,
      Assemblage F in cats, Assemblage G in rodents, and Assemblage H in pinnipeds. The
      factors determining host specificity are only partially understood, and clearly
      involve both the host and the parasite. Here, we review the results of in vitro
      and in vivo experiments, and clinical observations to highlight relevant
      biological and genetic differences between Assemblages, with a focus on human
      infection.

PMID- 29225146
TI  - Microbial diversity within the airway microbiome in chronic pediatric lung
      diseases.
AB  - The study of the airway microbiome in children is an area of emerging research,
      especially in relation to the role microbial diversity may play in acute and
      chronic inflammation. Three such pediatric airway diseases include cystic
      fibrosis, asthma, and chronic lung disease of prematurity. In cystic fibrosis,
      the presence of Pseudomonas spp. is associated with decreased microbial
      diversity. Decreasing microbial diversity is also associated with poor lung
      function. In asthma, early viral infections appear to drive changes in bacterial
      diversity which may be associated with asthma risk. Premature infants with
      Ureaplasma spp. are at higher risk for chronic lung disease due to inflammation.
      Microbiome changes due to prematurity also appear to affect the inflammatory
      response to viral infections post-natally. Importantly, microbial diversity can
      be measured using metataxonomic (e.g., 16S rRNA sequencing) and metagenomic
      (e.g., shotgun sequencing) approaches. A metagenomics approach may be preferable
      as it can provide further granularity of the sample composition, identifying the
      bacterial species or strain, information on additional microbial components,
      including fungal and viral components, information about functional genomics of
      the microbiome, and information about antimicrobial resistance mutations. Future
      studies of pediatric airway diseases incorporating these techniques may provide
      evidence for new treatment approaches for these vulnerable patient populations.

PMID- 29225148
TI  - Phylogeny and antimicrobial resistance in Neisseria gonorrhoeae isolates from Rio
      de Janeiro, Brazil.

PMID- 29225149
TI  - Detection and characterization of molecular-level collagen damage in
      overstretched cerebral arteries.
AB  - : It is well established that overstretch of arteries alters their mechanics and
      compromises their function. However, the underlying structural mechanisms behind
      these changes are poorly understood. Utilizing a recently developed collagen
      hybridizing peptide (CHP), we demonstrate that a single mechanical overstretch of
      an artery produces molecular-level unfolding of collagen. In addition, imaging
      and quantification of CHP binding revealed that overstretch produces damage
      (unfolding) among fibers aligned with the direction of loading, that damage
      increases with overstretch severity, and that the onset of this damage is closely
      associated with tissue yielding. These findings held true for both axial and
      circumferential loading directions. Our results are the first to identify stretch
      induced molecular damage to collagen in blood vessels. Furthermore, our approach
      is advantageous over existing methods of collagen damage detection as it is non
      destructive, readily visualized, and objectively quantified. This work opens the
      door to revealing additional structure-function relationships in arteries. We
      anticipate that this approach can be used to better understand arterial damage in
      clinically relevant settings such as angioplasty and vascular trauma.
      Furthermore, CHP can be a tool for the development of microstructurally-based
      constitutive models and experimentally validated computational models of arterial
      damage and damage propagation across physical scales. STATEMENT OF SIGNIFICANCE:
      Arteries play a critical role by carrying oxygen and essential nutrients
      throughout the body. However, trauma to the head and neck, as well as surgical
      interventions, can overstretch arteries and alter their mechanics. In order to
      better understand the cause of these changes, we employ a novel collagen
      hybridizing peptide (CHP) to study collagen damage in overstretched arteries. Our
      approach is unique in that we go beyond the fiber- and fibril-level and
      characterize molecular-level disruption. In addition, we image and quantify
      fluorescently-labeled CHP to reveal a new structure-property relationship in
      arterial damage. We anticipate that our approach can be used to better understand
      arterial damage in clinically relevant settings such as angioplasty and vascular
      trauma.

PMID- 29225150
TI  - Decellularised conjunctiva for ocular surface reconstruction.
AB  - : Conjunctival reconstruction is an integral component of ocular surface
      restoration. Decellularised tissues are frequently used clinically for tissue
      engineering. This study identifies porcine decellularised conjunctiva (PDC) and
      human decellularised conjunctiva (HDC) as promising substitutes for conjunctival
      reconstruction. PDC and HDC were nearly DNA-free, structurally intact and showed
      no cytotoxic effects in vitro, which was confirmed by DNA quantification,
      histology, transmission electron microscopy, collagen quantification and
      cytotoxicity assay. Comparing the biomechanical properties to amniotic membrane
      (AM), the most frequently applied matrix for ocular surface reconstruction today,
      the decellularised conjunctiva was more extensible and elastic but exhibited less
      tensile strength. The in vivo application in a rabbit model proofed significantly
      enhanced transplant stability and less suture losses comparing PDC and HDC to AM
      while none of the matrices induced considerable inflammation. Ten days after
      implantation, all PDC, 4 of 6 HDC but none of the AM transplants were completely
      integrated into the recipient conjunctiva with a partially multi-layered
      epithelium. Altogether, decellularised conjunctivas of porcine and human origin
      were superior to AM for conjunctival reconstruction after xenogeneic application
      in vivo. STATEMENT OF SIGNIFICANCE: Conjunctival integrity is essential for a
      healthy ocular surface and clear vision. Its reconstruction is required in case
      of immunological diseases, after trauma, chemical or thermal burns or surgery
      involving the conjunctiva. Due to limitations of currently used substitute
      tissues such as amniotic membrane, there is a need for the development of new
      matrices for conjunctival reconstruction. Decellularised tissues are frequently
      applied clinically for tissue engineering. The present study identifies porcine
      and human decellularised conjunctiva as biocompatible and well tolerated
      scaffolds with superior integration into the recipient conjunctiva compared to
      amniotic membrane. Decellularised conjunctiva depicts a promising substitute for
      conjunctival reconstruction in ophthalmology.

PMID- 29225151
TI  - Injectable in situ forming gel based on lyotropic liquid crystal for persistent
      postoperative analgesia.
AB  - : Local anesthetics have been widely used for postoperative analgesia. However,
      multiple injections or local infiltration is required due to the short half-lives
      of local anesthetics after single injection, which results in poor compliance and
      increasing medical expense. In this study, an in situ forming gel (ISFG) based on
      lyotropic liquid crystal was developed to deliver bupivacaine hydrochloride (BUP)
      for long-acting postoperative analgesia. BUP-ISFG was designed to be
      administrated as a precursor solution which would spontaneously transform into
      gel with well-defined internal nanostructures for sustained drug release at the
      site of administration when exposed to physiological fluid. A lamellar-hexagonal
      cubic phase transition occurred during the in situ gelation. The lamellar phase
      of the precursor solution endows it with low viscosity for good syringeability
      while the unique nanostructures of hexagonal and cubic phases of the in situ gel
      provide sustained drug release. Persistent analgesia effect in vivo was achieved
      with BUP-ISFG, and the plasma BUP concentration was found to be steadier compared
      to commercially available BUP for injection. In addition, the ISFG displayed
      acceptable biocompatibility and good biodegradability. The findings are positive
      about ISFG as a sustained release system for persistent postoperative analgesia.
      STATEMENT OF SIGNIFICANCE: To address the issue of insufficient postoperative
      analgesia associated with short half-lives of local anesthetics after single
      injection, an in situ forming gel (ISFG) based on lyotropic liquid crystal was
      developed to deliver bupivacaine hydrochloride (BUP) for postoperative analgesia
      over three days. The results demonstrated that persistent analgesia effect in
      vivo was achieved with single injection of BUP-ISFG, and the plasma BUP
      concentration was found to be steadier compared to commercially available BUP
      injection. The BUP-ISFG possessed a lamellar-hexagonal-cubic phase transition
      with corresponding crystal change in 3D nanostructure during the in situ
      gelation. The relationship between crystal nanostructure and carrier function,
      might provide some insights to the design and clinical applications of the drug
      delivery systems based on lyotropic liquid crystal.

PMID- 29225152
TI  - A Randomized Controlled Trial of Intra-Aortic Adenosine Infusion Before Release
      of the Aortic Cross-Clamp During Coronary Artery Bypass Surgery.
AB  - OBJECTIVES: To assess the feasibility, safety, and potential useful effect of
      adenosine as a postconditioning agent in patients undergoing coronary artery
      bypass grafting surgeries. DESIGN: Prospective randomized controlled study.
      SETTING: University hospital. PARTICIPANTS: The study comprised 60 patients
      scheduled for coronary artery bypass grafting surgery. INTERVENTIONS: Adenosine
      (postconditioning group) or placebo (control group). Adenosine infusion (150
      ug/kg/min) for 10 minutes via a cardioplegia needle into the aortic root was
      started 10 minutes before aortic cross-clamp removal. MEASUREMENTS AND MAIN
      RESULTS: Compared with the control group, ejection fraction, fractional
      shortening, cardiac index (2.9 +/- 0.3 v 2.2 +/- 0.3 L/min/m2, p = 0.032 at 60
      min postbypass) and diastolic function indices were significantly better in the
      postconditioning group at most time points in the postbypass period. Cardiac
      troponin I and creatine kinase-MB release and the inotropic score were
      significantly lower in the postconditioning group at most time points in the
      postoperative period. The need for intra-aortic balloon and epicardial pacing
      were comparable in both groups, whereas incidence of arrhythmia, duration of
      postoperative mechanical ventilation, and intensive care unit and total hospital
      stays were significantly lower in the postconditioning group. CONCLUSIONS:
      Adenosine postconditioning provided cardiac protection as evidenced by a
      favorable outcome on systolic and diastolic function indices, less cardiac
      troponin I and creatine kinase-MB release, lower incidence of arrhythmia, lower
      inotropic score, and shorter duration of postoperative mechanical ventilation and
      intensive care unit stay.

PMID- 29225153
TI  - Ipsilateral Shoulder Pain After Thoracotomy: Multifactorial in Cause, New
      Treatment Option.

PMID- 29225154
TI  - Development of a Predictive Model for Blood Transfusions and Bleeding During
      Liver Transplantation: An Observational Cohort Study.
AB  - OBJECTIVE: Orthotopic liver transplantation (OLT) frequently is associated with
      major blood loss and considerable transfusion requirements. The goal of this
      study was to define the risk factors for multiple transfusions and major bleeding
      during OLT and to help identify higher risk patients that could benefit from
      targeted interventions. DESIGN: OLTs were studied for this observational cohort
      study. SETTING: Community hospital. PARTICIPANTS: A total of 800 consecutive OLTs
      were studied. INTERVENTION: No intervention. MEASUREMENTS AND MAIN RESULTS:
      Baseline and intraoperative data were gathered. Multivariate logistic regression
      analyses were performed to find variables associated with 2 outcomes: transfusion
      of more than 2 units of red blood cells (RBC) and bleeding >=900 mL. Two
      nomograms were developed to predict individual risks. The overall intraoperative
      RBC transfusion was 0.6 +/- 1.4 units on average, and 61 surgeries (7.6%)
      received more than 2 units of RBC (4.5 +/- 1.9). Some variables were associated
      with the outcomes: 5 were associated with transfusion of more than 2 units of RBC
      (patient's height, starting hemoglobin concentration, starting bilirubin value,
      the use of a phlebotomy, and central venous pressure [CVP] at the time of vena
      cava clamping) and 3 with blood loss of >=900 mL (starting hemoglobin value,
      Child-Turcotte-Pugh score, and CVP at the time of vena cava clamping).
      Preclamping CVP showed the strongest association with both outcomes. Nomograms
      were developed to predict the individual OLT recipients' risk of requiring more
      than 2 units RBC and suffering from major bleeding. Among the variables
      associated with multiple RBC transfusions and major bleeding, 3 can lead to
      interventions: baseline hemoglobin value, the use of a phlebotomy, and the
      preclamping CVP. CONCLUSION: Some variables were able to predict the risk of
      multiple transfusions and major bleeding in this low bleeding liver
      transplantation population. Further studies based on these variables should be
      done to better define the role of targeted interventions in higher risk liver
      transplant recipients.

PMID- 29225155
TI  - Sufentanil Sublingual Tablet System for theManagement of Postoperative Pain
      afterVideo-Assisted Thoracic Surgery: APreliminary Clinical Experience.

PMID- 29225156
TI  - Performance of TCI Propofol Using the Schnider Model for Cardiac Surgery on
      Cardiopulmonary Bypass-A Pilot Study.
AB  - OBJECTIVE: This pilot study aimed to evaluate the performance of target
      controlled infusion (TCI) of propofol using the Schnider pharmacokinetic model in
      patients undergoing cardiac surgery requiring cardiopulmonary bypass. DESIGN:
      This was a prospective pharmacokinetic study. SETTING: A tertiary care hospital.
      PARTICIPANTS: This study is comprised of 10 patients, aged between 46 and 81, who
      underwent elective cardiac surgery requiring the use of cardiopulmonary bypass.
      INTERVENTIONS: Anesthetic technique was standardized. Hypnosis was maintained
      using TCI of propofol, titrated to achieve a bispectral index of 30 to 60.
      Calculated plasma propofol concentrations were recorded at 5 time points in
      total, before, during, and after cardiopulmonary bypass. Blood propofol
      concentration was measured at each of these time points. MEASUREMENTS AND MAIN
      RESULTS: The prediction errors and absolute prediction errors were calculated for
      each sample. From these, the median prediction error (MDPE) and its absolute
      value (MDAPE) were derived. Agreement between predicted and measured propofol
      concentrations was assessed using a Bland-Altman plot. Mean prediction errors
      were also compared pre-, on, and post-bypass using the generalized linear latent
      and mixed model. The MDPE and MDAPE were both found to be 45%, indicating
      significant bias toward under-prediction in the Schnider pharmacokinetic model.
      This bias was increased at an average propofol concentration of 4.5 MUg/mL and
      above. A significant decrease in mean prediction error was noted while on bypass
      (45.6%, 95% confidence intervals 9.2-82.1). CONCLUSIONS: The performance of the
      Schnider pharmacokinetic model for TCI propofol was poor, with a tendency toward
      under-prediction of blood propofol concentration, especially at higher average
      concentrations of propofol. While mitigating the risk of awareness, the risk of
      other adverse effects like hypotension and cardiorespiratory depression is
      increased. Patients should therefore be adequately monitored, and predicted
      plasma propofol concentrations taken in context with other patient parameters. A
      lower target concentration of propofol is probably sufficient to maintain an
      adequate depth of anesthesia as measured by BIS.

PMID- 29225157
TI  - The effect of amniotic membrane grafting on healing and wound strength after
      strabismus surgery in a rabbit model.
AB  - BACKGROUND: Amniotic membrane grafts (AMGs) are used, with mixed results, as a
      platform for ocular healing and to reduce pathologic scarring. This study
      evaluated wound tensile strength and histopathologic changes after strabismus
      surgery with AMGs in 20 New Zealand white rabbits. METHODS: All subjects
      underwent 4 mm inferior rectus hang-back recessions to both eyes. The right eyes
      served as controls. Ten left eyes (group 1) received processed dehydrated
      amniotic membrane allografts (Ambiodry2, IOP Inc, Costa Mesa, CA) and ten left
      eyes (group 2) received cryopreserved human amniotic membrane allografts
      (AmnioGraft, Bio-Tissue, Miami, FL) between the sclera and muscle insertion and
      between the muscle and repositioned conjunctiva. At postoperative month 1,
      tensile strengths of the muscle-globe and conjunctiva-globe attachments were
      measured, and histopathologic analysis of each eye was performed. RESULTS: In
      group 1 the mean tensile strength of the muscle-globe attachments was 441.4 +/-
      274.4 g; of the conjunctiva-globe attachments, 640.3 +/- 266.4 g. In the control
      eyes, the comparable values were 365.8 +/- 199.8 g and 595.2 +/- 315.3 g,
      respectively (P = 0.19, P = 0.13). In group 2 the mean tensile strengths were 456
      +/- 297.5 g and 608.2 +/- 306.7 g, compared with control values of 352.7 +/-
      114.8 g and 583.8 +/- 347.1 g (P = 0.43, P = 0.45). CONCLUSIONS: There was no
      significant change in tensile strength of the muscle insertion using AMGs. In a
      rabbit model, AMGs do not reduce inflammation or improve scar formation 1 month
      after strabismus surgery.

PMID- 29225158
TI  - Exendin-4 partly ameliorates - hyperglycemia-mediated tissue damage in lungs of
      streptozotocin-induced diabetic mice.
AB  - Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, - plays anti
      inflammatory role in atherosclerosis, and has surfactant-releasing effects in
      lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to
      investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in
      diabetic mice. BALB/c male mice were divided into four groups. The first group
      was given only citrate buffer, the second group was given only exendin-4, the
      third group was given only streptozotocin (STZ), and the fourth group was given
      both exendin-4 and STZ. Exendin-4 (3MUg/kg) was administered daily by
      subcutaneous injection for 30days after mice were rendered diabetic with a single
      dose of STZ (200mg/kg). Structural alterations, oxidative stress, apoptosis,
      insulin signaling and expressions of prosurfactant-C, alpha-smooth muscle actin,
      collagen-I and fibronectin were evaluated in lung tissue. Diabetic mice lungs
      were characterized by induced oxidative stress, apoptosis, edema, and cell
      proliferation. They had honeycomb-like alveoli, thicker alveolar walls, and
      hypertrophic pneumocytes. Although exendin-4 treatment improved pulmonary edema,
      apoptosis, oxidative stress, and lung injury, it led to the disrupted insulin
      signaling and interstitial collagen accumulation in the lungs of diabetic mice.
      Exendin-4 ameliorates hyperglycemia-mediated lung damage by reducing glucose, 
      oxidative stress and stimulating cell proliferation. However, exendin-4 led to
      increased lung injury partly by reducing insulin signaling - and collagen
      accumulation around pulmonary vasculature in diabetic mice.

PMID- 29225159
TI  - Histopathology of periarticular non-hereditary heterotopic ossification.
AB  - In the mature adult skeleton, new bone formation is normally restricted to
      regeneration of osseous tissue at sites of fracture. However, heterotopic
      ossification, or the formation of bone outside the normal skeleton, can occur
      within muscle, adipose, or fibrous connective tissue. Periarticular non
      hereditary heterotopic ossification (NHHO) may occur after musculoskeletal
      trauma, following CNS injury, with certain arthropathies, or following injury or
      surgery that is often sustained in the context of age-related pathology. The
      histological mechanism of bone development in these forms of heterotopic
      ossification has thus far been uncharacterized. We performed a histological
      analysis of 90 bone specimens from 18 patients with NHHO secondary to defined
      precipitating conditions, including traumatic brain injury, spinal cord injury,
      cerebrovascular accident, trauma without neurologic injury, and total hip or knee
      arthroplasty. All bone specimens revealed normal endochondral osteogenesis at
      heterotopic sites. We defined the order of sequence progression in NHHO lesion
      formation as occurring through six distinct histological stages: (1) perivascular
      lymphocytic infiltration, (2) lymphocytic migration into soft tissue, (3)
      reactive fibroproliferation, (4) neovascularity, (5) cartilage formation, and (6)
      endochondral bone formation. This study provides the first systematic evaluation
      of the predominant histopathological findings associated with multiple forms of
      NHHO and shows that they share a common mechanism of lesion formation.

PMID- 29225160
TI  - Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through
      the SRC3/IGF1R/AKT pathway.
AB  - Steroid receptor co-activator3 (SRC3) has been known to severe as an androgen
      receptor (AR) coactivator and is involved in the prostate cancer progression. Non
      coding RNA (ncRNA) plays an important role in the cancer progression. However,
      the mechanism underlying the relationship between ncRNA and AR coactivators is
      still unclear. Here, we found a ncRNA, Nuclear Enriched Abundant Transcript 1
      (NEAT1), was able to interact with SRC3 in the prostate cancer cell lines. NEAT1
      can upregulate the AKT phosphorylation via a SRC3/IGF1R pathway. In function,
      NEAT1 promoted the prostate cancer cell growth through IGF1R/AKT signaling
      pathway. The NEAT1, SRC3, and IGF1R were highly expressed in the patients'
      samples of prostate cancer. Therefore, we found a novel SRC3 binding ncRNA that
      can promote the prostate cancer cell growth through SRC3/IGF1R/AKT pathway.

PMID- 29225161
TI  - Self-Efficacy and Pressure Ulcer Prevention After Spinal Cord Injury-Results From
      a Nationwide Community Survey in Switzerland (SwiSCI).
AB  - BACKGROUND: Pressure ulcers (PUs) are a common and severe health condition in
      persons with spinal cord injury (SCI). Skin-care strategies for PU prevention are
      usually provided during initial rehabilitation. However, individuals with SCI
      often do not perform these strategies continuously, especially after discharge.
      The influence of psychological factors such as general self-efficacy (GSE) on the
      performance of PU prevention behavior has not yet been sufficiently explored.
      OBJECTIVE: To investigate whether persons with greater levels of GSE are more
      likely to perform skin-care strategies for PU prevention regularly. DESIGN:
      Nationwide cross-sectional survey within the Swiss Spinal Cord Injury Cohort
      Study. SETTING: Community setting, data collection between 2011 and 2013.
      PARTICIPANTS: A total of 456 subjects with a traumatic or nontraumatic SCI living
      in Switzerland. METHODS: Associations between GSE and PU prevention behavior were
      analyzed by multivariate proportional odds regression models, including potential
      sociodemographic, lesion-related, and lifestyle-related confounders without and
      with interaction terms between GSE and potential effect modifiers. MAIN OUTCOME
      MEASUREMENTS: Self-efficacy was assessed by the GSE scale comprising 10 items. PU
      preventive behavior was operationalized using 5 items of an adapted version of
      the Spinal Cord Injury Lifestyle scale. Both measurements were components of a
      self-administered questionnaire. RESULTS: Based on the regression model without
      interaction terms, GSE levels were not associated with skin-care PU prevention.
      After we included interaction terms, the final model showed statistically
      significant associations between GSE and 3 skin-care items with odds ratios
      ranging from 1.09 to 1.17 (all P < .001). The slightly positive effect of GSE on
      PU prevention behavior was restricted to persons who sustained their SCI at a
      younger age. CONCLUSIONS: GSE was generally not associated with skin-care PU
      prevention behavior among persons with SCI in this study. In further research, it
      might be of interest to assess SCI-specific concepts of self-efficacy. LEVEL OF
      EVIDENCE: III.

PMID- 29225162
TI  - Can Ultrasound Be Used to Improve the Palpation Skills of Physicians in Training?
      A Prospective Study.
AB  - BACKGROUND: Accurate diagnosis of musculoskeletal disorders relies heavily on the
      physical examination, including accurate palpation of musculoskeletal structures.
      The literature suggests that there has been a deterioration of physical
      examination skills among medical students and residents, in part due to increased
      reliance on advanced imaging. It has been shown that knowledge of musculoskeletal
      anatomy and physical examination skills improve with the use of ultrasound;
      however, the literature is limited. OBJECTIVE: To determine whether ultrasound
      can improve the ability of physicians in training (residents) to palpate the long
      head of the biceps tendon (LHBT) in the bicipital groove. DESIGN: Prospective
      study design. SETTING: Tertiary care center. PARTICIPANTS: Ten physical medicine
      and rehabilitation residents served as subjects. Exclusion criteria included the
      presence of any condition that precluded their ability to palpate. Three
      volunteers were used as models. Model exclusion criteria included anything that
      distorted normal shoulder anatomy or inhibited examiner palpation. Three
      investigators with experience performing diagnostic musculoskeletal ultrasound
      were used to confirm palpation attempts. METHODS: Subjects attempted to palpate
      the LHBT bilaterally in the bicipital groove of each model. Investigators
      assessed the accuracy of the palpation attempt using real-time ultrasonography.
      Subjects participated in a 30-minute ultrasound-assisted training session
      learning how to palpate the LHBT in the bicipital groove with ultrasound
      confirmation. After the ultrasound training session, subjects again attempted to
      palpate the LHBT in the bicipital groove of each model with investigator
      confirmation. MAIN OUTCOME MEASUREMENTS: LHBT palpation accuracy rates
      preintervention versus postintervention. RESULTS: Pretraining LHBT palpation
      accuracy was 20% (12/60 attempts). Post-ultrasound training session accuracy was
      51.7% (31/60 attempts; P <= .001). CONCLUSIONS: Our findings demonstrate that
      palpation accuracy improves after ultrasound assisted LHBT palpation training.
      These data suggest that the use of ultrasound may be beneficial when teaching
      musculoskeletal palpation skills to health care professionals. LEVEL OF EVIDENCE:
      II.

PMID- 29225163
TI  - Impact of Dose-Adjusted Melphalan in Obese Patients Undergoing Autologous Stem
      Cell Transplantation.
AB  - Limited guidance exists for dosing melphalan for autologous stem cell
      transplantation (ASCT) in the obese patient population, because the current
      literature reports conflicting clinical outcomes between obese and nonobese
      patients. In 2014, the American Society for Blood and Marrow Transplantation
      published conditioning chemotherapy dosing guidelines for obese patients and
      recommended dosing of melphalan using actual body weight (ABW) in the body
      surface area calculation. The practice at Barnes-Jewish Hospital has consistently
      been to dose melphalan using adjusted body weight (AdBW), with a 20% correction
      when a patient weighs >=120% of his or her ideal body weight (IBW). The purpose
      of this study was to compare outcomes of melphalan ASCT in patients with multiple
      myeloma between obese (>=120% IBW) and nonobese (<120% IBW) populations. This
      retrospective, single-center study included adult patients with multiple myeloma
      undergoing first ASCT with melphalan conditioning between January 2009 and
      December 2012. Patient demographic data, transplantation characteristics, and
      clinical outcomes were collected. The primary outcome was 3-year event-free
      survival (EFS). Secondary outcomes included response at 100 days post
      transplantation, 3-year overall survival, treatment-related mortality (TRM), time
      to neutrophil engraftment, and hospital length of stay (LOS). To ensure that
      melphalan dosage adjustment in the obese population did not impact efficacy, the
      primary outcome was assessed using a noninferiority design, with a predetermined
      noninferiority margin of 7%. Assuming a 70% 3-year EFS in the nonobese
      population, a noninferiority margin of 7%, a power of 80%, and an alpha value of
      .05, an analysis of 280 patients was required. A total of 270 patients, including
      171 (63%) obese patients and 99 (37%) nonobese patients, met our inclusion
      criteria. Baseline characteristics were well matched between the 2 cohorts,
      including high-risk cytogenetics, disease severity at diagnosis, and use of
      maintenance therapy, with the only detectable differences related to weight
      itself. The 3-year EFS was 41% for the total cohort, with fewer events occurring
      in the obese cohort compared with the nonobese cohort (51% versus 40%; P =
      .0025). The 95% lower confidence limit established noninferiority. High-risk
      cytogenetics, disease severity at diagnosis, and therapy response pre- and post
      ASCT were all associated with significantly shorter EFS. No between-group
      differences in TRM, time to engraftment, or hospital LOS were noted. This
      retrospective, single-center study found that using AdBW to dose melphalan in
      obese patients was not inferior to the nonobese population in terms of 3-year
      EFS. This study adds to the limited evidence on melphalan dosing and suggests
      that transplantation efficacy is not affected by AdBW dosing in obese patients.
      Further studies are needed to provide additional insight into the pharmacokinetic
      differences and best dosing practices for obese patients.

PMID- 29225164
TI  - Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation
      in Gray Zone Lymphoma: A US Multicenter Collaborative Study.
AB  - High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto
      HCT) has been anecdotally prescribed in gray zone lymphoma (GZL), showing
      encouraging efficacy. We conducted a multicenter retrospective study aimed at
      assessing outcomes after auto-HCT in 32 patients with GZL treated at 9
      transplantation centers in the United States. The median age of patients at
      transplantation was 38 years (range, 18 to 70 years), and the majority were male
      (n = 21; 66%). The median number of lines of therapy before transplantation was 2
      (range, 1 to 4). BEAM was the most commonly prescribed regimen (n = 23; 72%). The
      median duration of follow-up for surviving patients was 34 months (range, 1 to
      106 months). Median overall survival (OS) was not reached. The 3-year progression
      free survival (PFS) and OS for all patients were 69% and 78%, respectively. Three
      year PFS and OS were 100% for patients who received only 1 line of therapy before
      auto-HCT versus 65% (PFS, P = .25) and 75% (OS, P = .39) for those receiving >1
      line. The cumulative incidence of relapse/progression was 4% at 1 year post
      transplantation and 31% at 3 years post-transplantation. The 3-year nonrelapse
      mortality was 0%. These findings suggest that HDT and auto-HCT is an effective
      treatment in patients with GZL. Our findings ideally require confirmation in a
      larger cohort of patients, preferably in the setting of large prospective
      multicenter randomized controlled trials. However, we acknowledge that such
      studies could be difficult to conduct in patients with GZL owing to the disease's
      rarity. Alternatively, a multicenter prospective study that includes tissue
      banking and a data registry is warranted to help better understand the biology
      and natural history of the disease.

PMID- 29225165
TI  - Cross talk between TP53 and c-Myc in the pathophysiology of Diamond-Blackfan
      anemia: Evidence from RPL11-deficient in vivo and in vitro models.
AB  - Mutations in genes encoding ribosomal proteins have been identified in Diamond
      Blackfan anemia (DBA), a rare genetic disorder that presents with a prominent
      erythroid phenotype. TP53 has been implicated in the pathophysiology of DBA with
      ribosomal protein (RP) L11 playing a crucial role in the TP53 response.
      Interestingly, RPL11 also controls the transcriptional activity of c-Myc, an
      oncoprotein that positively regulates ribosome biogenesis. In the present study,
      we analyzed the consequences of rpl11 depletion on erythropoiesis and ribosome
      biogenesis in zebrafish. As expected, Rpl11-deficient zebrafish exhibited defects
      in ribosome biogenesis and an anemia phenotype. However, co-inhibition of Tp53
      did not alleviate the erythroid aplasia in these fish. Next, we explored the role
      of c-Myc in RPL11-deficient cellular and animal models. c-Myc and its target
      nucleolar proteins showed upregulation and increased localization in the head
      region of Rpl11-deficient zebrafish, where the morphological abnormalities and
      tp53 expression were more pronounced. Interestingly, in blood cells derived from
      DBA patients with mutations in RPL11, the biogenesis of ribosomes was defective,
      but the expression level of c-Myc and its target nucleolar proteins was
      unchanged. The results suggest a model whereby RPL11 deficiency activates the
      synthesis of c-Myc target nucleolar proteins, which subsequently triggers a p53
      response. These results further demonstrate that the induction of Tp53 mediates
      the morphological, but not erythroid, defects associated with RPL11 deficiency.

PMID- 29225166
TI  - Apatinib inhibits migration and invasion as well as PD-L1 expression in
      osteosarcoma by targeting STAT3.
AB  - The cure rate of osteosarcoma has not improved in the past 30 years. The new
      treatments and drugs is urgently needed, especially for metastatic osteosarcoma.
      Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects
      in various tumors. It is hypothesised that combining checkpoint inhibitor
      immunotherapies with antiangiogenic treatment may have a synergistic effect and
      enhance the efficacy of both treatments. However, its underlying mechanism remain
      largely uninvestigated. To investigate the clinical significance of vascular
      endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD
      L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma
      specimens by immunohistochemistry. Meanwhile, we analyzes their correlation with
      the metastatic behavior and overall survival (OS). We also investigate the
      effects of Apatinib on migration and invasion of osteosarcoma cells and its
      underlying mechanism in vitro and in vivo. In our study, the positive rates of
      the VEGFR2 and PD-L1 expression are 64.5% (60/93) and 35.5% (33/93),
      respectively. A significant correlation is detected between VEGFR2 and PD-L1
      expression (P = 0.009). Receiver-operating characteristic (ROC) curves analysis
      indicates the predictive value of the two markers in tumor metastasis, and both
      PD-L1 and VEGFR2 are negatively correlated with OS. Transwell assays reveals that
      VEGFR2 inhibition attenuates migration and invasion of osteosarcoma cells.
      Mechanistically, we demonstrate that Apatinib attenuates migration and invasion
      by suppressing epithelial-mesenchymal transition (EMT) and inactivating STAT3.
      Additionally, Apatinib reduces PD-L1 expression in osteosarcoma cells. Apatinib
      markedly weakens pulmonary metastatic potential of osteosarcoma in vivo. In
      conclusion, our study reveals a pro-metastatic functional mechanism for VEGFR2 in
      osteosarcoma. Furthermore, we demonstrate that Apatinib exerts anti-tumor effect
      not only through antiangiogenic effect, but also via suppressing immune escape,
      which may represent a potential therapeutic target for metastatic osteosarcoma.

PMID- 29225167
TI  - Adenovirus infection induces HuR relocalization to facilitate virus replication.
AB  - HuR is an RNA-binding protein of the embryonic lethal abnormal vision (ELAV)
      family, which binds to the AU-rich element (ARE) in the 3'-untranslated region
      (UTR) of certain mRNAs and is involved in the nucleo-cytoplasmic export and
      stabilization of ARE-mRNAs. The cytoplasmic relocalization of ARE-mRNAs with
      several proteins such as HuR and pp32 increases in cells transformed by the
      adenovirus oncogene product E4orf6. Additionally, these ARE-mRNAs were stabilized
      and acquired the potential to transform cells. Although, the relocalization of
      HuR and the stabilization of ARE-mRNAs are crucial for cell transformation,
      evidence regarding the relationship of HuR and ARE-mRNAs with adenovirus
      replication is lacking. In this report, we demonstrate that adenovirus infection
      induces the relocation of HuR to the cytoplasm of host cells. Analysis using the
      luciferase-ARE fusion gene and the tetracycline (tet)-off system revealed that
      the process of stabilizing ARE-mRNAs is activated in adenovirus-infected cells.
      Heat shock treatment or knockdown-mediated depletion of HuR reduced adenovirus
      production. Furthermore, expression of ARE-including viral IVa2 mRNA, decreased
      in HuR-depleted infected cells. These results indicate that HuR plays an
      important role in adenovirus replication, at least in part, by up-regulating IVa2
      mRNA expression and that ARE-mRNA stabilization is required for both
      transformation and virus replication.

PMID- 29225168
TI  - Cortistatin attenuates angiotensin II-induced abdominal aortic aneurysm through
      inactivation of the ERK1/2 signaling pathways.
AB  - Abdominal aortic aneurysm (AAA) is a fatal disease that is associated with
      chronic inflammation in the vessel wall. Cortistatin is implicated in
      inflammation, vascular smooth muscle cell migration and other cardiovascular
      pathologies. But, the hypothetical effect of cortistatin on AAA remains
      uncertain. We investigated the effect of cortistatin administration to
      angiotensin (Ang) II-induced AAA formation in apolipoprotein E deficient (Apoe-/
      ) mice. We showed that cortistatin administration significantly suppresses
      incidence and severity of AAA in Apoe-/- mice. A significant increase in
      macrophage infiltration, excretion of inflammatory cytokines, activities and
      expression levels of MMP2 and MMP9, reactive oxygen species levels and cell
      apoptosis in aneurysmal aortic wall of Apoe-/- mice infused with Ang-II, and
      these events were significantly alleviated by co-treatment with cortistatin.
      Mechanistic studies showed that the protective effects of cortistatin were
      related to the blocking of ERK1/2 signaling pathways, while does not was not
      actually affect JNK, P38 phosphorylation. In conclusion, cortistatin appears to
      play an essential role in the formation of AAA and indicate cortistatin may as
      novel therapeutic option for AAA.

PMID- 29225169
TI  - Inhibition of Orai1-mediated Ca2+ entry limits endothelial cell inflammation by
      suppressing calcineurin-NFATc4 signaling pathway.
AB  - Orai1-dependent Ca2+ entry plays an essential role in inflammatory response
      through regulating T cell and macrophage activation and neutrophil infiltration.
      However, whether Orai1 Ca2+ entry contributes to endothelial activation, one of
      the early steps of vascular inflammation, remains elusive. In the present study,
      we observed that knockdown of Orai1 reduced, whereas overexpression of Orai1
      potentiated, TNFalpha-induced expression of adhesion molecules such as ICAM-1 and
      VCAM-1 in HUVECs, and subsequently blocked adhesion of monocyte to HUVECs. In
      vivo, Orai1 downregulation attenuated TNFalpha-induced ICAM-1 and VCAM-1
      expression in mouse aorta and the levels of pro-inflammatory cytokines in the
      serum. In addition, Orai1 knockdown also dramatically decreased the expression of
      pro-inflammatory cytokines and neutrophil infiltration in the lung after TNFalpha
      treatment, and thus protected lung tissue injury. Notably, among all isoforms of
      nuclear factor of activated T cells (NFATs), TNFalpha only triggered NFATc4
      nuclear accumulation in HUVECs. Knockdown of Orai1 or inhibition of calcineurin
      prevented TNFalpha-induced NFATc4 nuclear translocation and reduced ICAM-1 and
      VCAM-1 expression in HUVECs. Overexpression of NFATc4 further enhanced ICAM-1 and
      VCAM-1 expression induced by TNFalpha. Our study demonstrates that Orai1-Ca2+
      calcineurin-NFATc4 signaling is an essential inflammatory pathway required for
      TNFalpha-induced endothelial cell activation and vascular inflammation.
      Therefore, Orai1 may be a potential therapeutic target for treatment of
      inflammatory diseases.

PMID- 29225170
TI  - Dihydromyricetin sensitizes human acute myeloid leukemia cells to retinoic acid
      induced myeloid differentiation by activating STAT1.
AB  - The success of all-trans retinoic acid (ATRA) in differentiation therapy for
      patients with acute promyelocytic leukemia (APL) highly encourages researches to
      apply a new combination therapy based on ATRA. Therefore, research strategies to
      further sensitize cells to retinoids are urgently needed. In this study, we
      showed that Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, exhibited a
      strong synergy with ATRA to promote APL NB4 cell differentiation. We observed
      that DMY sensitized the NB4 cells to ATRA-induced cell growth inhibition, CD11b
      expression, NBT reduction and myeloid regulator expression. PML-RARalpha might
      not be essential for DMY-enhanced differentiation when combined with ATRA, while
      the enhanced differentiation was dependent on the activation of p38-STAT1
      signaling pathway. Taken together, our study is the first to evaluate the synergy
      of DMY and ATRA in NB4 cell differentiation and to assess new opportunities for
      the combination of DMY and ATRA as a promising approach for future
      differentiation therapy.

PMID- 29225171
TI  - CtBP represses Dpp signaling as a dimer.
AB  - C-terminal binding protein (CtBP) is a highly conserved transcriptional co
      repressor in animal development and human diseases. In Drosophila, CtBP is
      critical for fly development and is thought to exert its repressive roles in many
      signaling pathways including Dpp/BMP pathway. Here we provide evidence that
      although wild type CtBP negatively and dominantly influences Dpp signaling in fly
      presumptive wings, mutant CtBP unable to form dimer does not, indicating that
      dimerization is required for the repression role of CtBP in Dpp signaling in
      vivo.

PMID- 29225172
TI  - Role of allograft inflammatory factor-1 in bleomycin-induced lung fibrosis.
AB  - Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages
      infiltrating the area around the coronary arteries in a rat ectopic cardiac
      allograft model. We previously reported that AIF-1 is associated with the
      pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft
      versus-host disease mice. Here, we used an animal model of bleomycin-induced lung
      fibrosis to analyze the expression of AIF-1 and examine its function in lung
      fibrosis. The results showed that AIF-1 was expressed on lung tissues,
      specifically macrophages, from mice with bleomycin-induced lung fibrosis.
      Recombinant AIF-1 increased the production of TGF-beta which plays crucial roles
      in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant
      AIF-1 also increased both the proliferation and migration of lung fibroblasts
      compared with control group. These results suggest that AIF-1 plays an important
      role in the mechanism underlying lung fibrosis, and may provide an attractive new
      therapeutic target.

PMID- 29225173
TI  - New insights into the membrane association mechanism of the glycosyltransferase
      WaaG from Escherichia coli.
AB  - Monotopic glycosyltransferases (GTs) interact with membranes via electrostatic
      interactions. The N-terminal domain is permanently anchored to the membrane while
      the membrane interaction of the C-terminal domain is believed to be weaker so
      that it undergoes a functionally relevant conformational change upon donor or
      acceptor binding. Here, we studied the applicability of this model to the
      glycosyltransferase WaaG. WaaG is involved in the synthesis of
      lipopolysaccharides (LPS) in Gram-negative bacteria and was previously
      categorized as a monotopic GT. We analyzed the binding of WaaG to membranes by
      stopped-flow fluorescence and NMR diffusion experiments. We find that
      electrostatic interactions are required to bind WaaG to membranes while mere
      hydrophobic interactions are not sufficient. WaaG senses the membrane's surface
      charge density but there is no preferential binding to specific anionic lipids.
      However, the binding is weaker than expected for monotopic GTs but similar to
      peripheral GTs. Therefore, WaaG may be a peripheral GT and this could be of
      functional relevance in vivo since LPS synthesis occurs only when WaaG is
      membrane-bound. We could not observe a C-terminal domain movement under our
      experimental conditions.

PMID- 29225174
TI  - Photopolymerized maleilated chitosan/methacrylated silk fibroin
      micro/nanocomposite hydrogels as potential scaffolds for cartilage tissue
      engineering.
AB  - Hydrogels composed of natural materials exhibit great application potential in
      artificial scaffolds for cartilage repair as they can resemble the extracellular
      matrices of cartilage tissues comprised of various glycosaminoglycan and
      collagen. Herein, the natural polymers with vinyl groups, i.e. maleilated
      chitosan (MCS) and methacrylated silk fibroin (MSF) micro/nanoparticles, were
      firstly synthesized. The chemical structures of MCS and MSF micro/nanoparticles
      were investigated using Fourier transform infrared (FTIR) spectroscopy, proton
      nuclear magnetic resonance (1H NMR) spectroscopy, and X-ray photoelectron
      spectroscopy (XPS). Then MCS/MSF micro/nanocomposite hydrogels were prepared by
      the photocrosslinking of MCS and MSF micro/nanoparticles in aqueous solutions in
      the presence of the photoinitiator Darocur 2959 under UV light irradiation. A
      series of properties of the MCS/MSF micro/nanocomposite hydrogels including
      rheological property, equilibrium swelling, sol content, compressive modulus, and
      morphology were examined. The results showed that these behaviors could be
      tunable via the control of MSF content. When the MSF content was 0.1%, the
      hydrogel had the compressive modulus of 0.32+/-0.07MPa, which was in the range of
      that of articular cartilage. The in vitro cytotoxic evaluation and cell culture
      of the micro/nanocomposite hydrogels in combination with mouse articular
      chondrocytes were also investigated. The results demonstrated that the
      micro/nanocomposite hydrogels with TGF-beta1 was biocompatible to mouse articular
      chondrocytes and could support cells attachment well, indicating their potential
      as tissue engineering scaffolds for cartilage repair.

PMID- 29225175
TI  - PgTeL, the lectin found in Punica granatum juice, is an antifungal agent against
      Candida albicans and Candida krusei.
AB  - The pomegranate (Punica granatum) sarcotesta contains a chitin-binding lectin
      (PgTeL) with antibacterial activity against human pathogenic species. In this
      work, the structural stability of PgTeL was evaluated by fluorimetric analysis
      and the lectin was evaluated for cytotoxicity to human peripheral blood
      mononuclear cells (PBMCs) and antifungal activity against Candida albicans and
      Candida krusei. PgTeL folding was impaired when lectin was incubated at pH>=6.0.
      On the other hand, the lectin did not undergo unfolding even when heated at 100
      degrees C. PgTeL (1, 10, and 100MUg/mL) was not cytotoxic to PBMCs. Antifungal
      activity was detected for C. albicans (MIC: 25MUg/mL; MFC: 50MUg/mL) and C.
      krusei (MIC and MFC of 12.5MUg/mL). Treatment of yeast cells with PgTeL resulted
      in decrease of intracellular ATP content even at sub-inhibitory concentrations
      (1/2MIC and 1/4MIC) and induced lipid peroxidation. In addition, PgTeL damaged
      the integrity of fungal cell wall of both species, with more pronounced effects
      in C. krusei. The lectin showed significant antibiofilm activity on C. albicans
      at sub-inhibitory concentrations (0.195 and 0.39MUg/mL). In conclusion, PgTeL is
      an anti-Candida agent whose action mechanism involves oxidative stress, energetic
      collapse, damage to the cell wall and rupture of yeast cells.

PMID- 29225176
TI  - Synthesis of biaryls using palladium nanoparticles immobilized on metformine
      functionalized polystyrene resin as a reusable and efficient nanocatalyst.
AB  - This study includes the procedure performed for the Pd@PS-Met preparation as a
      novel polymeric nanocatalyst, in which to entrapped palladium nanoparticles (Pd
      NPs) without agglomeration, metformine groups are applied (as linkers). The
      obtained catalyst could be evaluated using transmission electron microscopy
      (TEM), wavelength-dispersive X-ray spectroscopy (WDX), scanning electron
      microscopy (SEM), X-ray powder diffraction (XRD), inductively coupled plasma
      (ICP), fourier transform infrared (FTIR), and Energy-dispersive X-ray
      spectroscopy (EDS). For Suzuki cross-coupling reaction, the catalyst showed an
      excellent catalytic stability and activity in water under ambient condition.
      Additionally, this novel entrapped palladium catalyst was recovered by an easy
      filtration and reapplied several times without considerable activity loss.

PMID- 29225177
TI  - Chitosan based hydrogel assisted spongelike calcium phosphate mineralization for
      in-vitro BSA release.
AB  - New chitosan-g- poly (3-sulfopropyl methacrylate), CHI-g-P(SPMA), hydrogel was
      prepared by free radical polymerization process and investigated as a template
      for biomimetic spongelike calcium phosphate mineralization in a solution
      mimicking physiological condition. Infrared spectroscopy, scanning electron
      microscopy, X-ray diffraction and transmission electron microscopy confirmed the
      predominant formation of rod-like hydroxyapatite. The swelling behavior of the
      nanocomposite was evaluated at different pHs and different saline concentrations.
      Bovine serum albumin (BSA), as a model protein drug, was loaded in the CHI-g
      P(SPMA)/calcium phosphate hybrid. The BSA release behavior was investigated and
      the results suggested CHI-g-P(SPMA)/calcium phosphate hybrid as controlled
      release carrier. These results suggest that next generation of polysaccharides
      based hybrid materials could be interesting for biomedical applications.

PMID- 29225178
TI  - Network formation of Moringa oleifera gum by radiation induced crosslinking:
      Evaluation of drug delivery, network parameters and biomedical properties.
AB  - The present article is an attempt to explore the potential of the Moringa
      oleifera gum polysaccharides in network formation with poly(acrylic acid) by
      radiation induced crosslinking to develop the hydrogel for slow drug delivery
      applications. Polymers were characterized by Cryo-SEM, AFM and 13C NMR
      techniques. Furthermore, drug delivery, network formation and some biomedical
      properties like blood compatibility, antioxidant activity, mucoadhesion and gel
      strength of the hydrogels were also determined. The release of ciprofloxacin
      occurred through non-Fickian diffusion mechanism and release profile best fitted
      in Korsmeyer-Peppas kinetic model. The hydrogels were found to be pH responsive,
      mucoadhesive non-thrombogenic, non-haemolytic, and antioxidant in nature. The
      crosslink density (rho) and the mesh size (xi) of the polymer network was
      observed 3.81*10-5mol/cm3 and 38.77nm respectively in pH 7.4 solution.

PMID- 29225179
TI  - Synthesis of novel benzodioxane midst piperazine moiety decorated chitosan silver
      nanoparticle against biohazard pathogens and as potential anti-inflammatory
      candidate: A molecular docking studies.
AB  - Nanoparticles (NPs) are currently being investigated along with the use of
      biodegradable polymer containing active agents in many areas of medicine for
      targeted applications. The present study was aimed to synthesize novel compound
      Benzodioxane midst piperazine (BP) and characterization of a BP decorated
      chitosan silver nanoparticles (BP*C@AgNPs) and shown effective against hazardous
      pathogens, and also having anti-inflammatory property. It was further evaluated
      for molecular docking proofs, and toxicity. The BP*C@AgNPs had spherical shape
      with size of 36.6nm with wide biocidal activity against hazardous Gram-positive
      and Gram-negative bacteria with excellent inhibition at 100MUg/mL for S. aureus
      (10.08+/-0.05mm ZOI), and E. coli (10.03+/-0.04mm ZOI) compared to antibiotic
      Streptomycin. The anti-inflammatory activity exhibited IC50 value of 71.61+/
      1.05MUg/mL for BP*C@AgNPs compared to indomethacin (IC50=40.15+/-1.21MUg/mL).
      Also, the docking study of BP showed excellent score for COX1 and DNA gyrase.
      This in silico study confirmed the achieved efficacy of BP, with less toxicity
      against normal PMBCs in vitro and in vivo studies. This study concludes that, the
      novel synthesized BP*C@AgNPs had excellent biocidal property and as anti
      inflammatory candidate revealed by docking studies, it confirms BP*C@AgNPs for
      first-class therapeutic applications in the area of medicinal nanotechnology for
      the coming days.

PMID- 29225180
TI  - Influence of drying of chara cellulose on length/length distribution of
      microfibrils after acid hydrolysis.
AB  - Chara is a genus of freshwater alga that is evolutionarily observed at the
      aquatic-terrestrial boundary, whose cellulose microfibrils are similar to those
      of terrestrial plants regarding the crystallinity and biosynthesis of cellulose.
      Oven-dried and never-dried celluloses samples were prepared from chara.
      Terrestrial plant cellulose samples were used as references. The lengths and
      length distributions of oven-dried and never-dried chara cellulose microfibrils
      after acid hydrolysis with or without pretreatment by 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation, which was used for
      efficient fibrillation of acid-hydrolyzed products, were observed by transmission
      electron microscopy. All terrestrial plant celluloses and oven-dried chara
      cellulose had short nanocrystal-like morphologies of 100-300 nm in length after
      acid hydrolysis. In contrast, the never-dried chara cellulose had much longer
      microfibrils of ~970 nm in length after acid hydrolysis. These results indicated
      that disordered regions present periodically along the cellulose microfibrils,
      which cause the formation of cellulose nanocrystals after acid hydrolysis, are
      not present in inherent chara cellulose microfibrils in water, but are formed
      artificially under drying or dehydration conditions.

PMID- 29225181
TI  - The effect of green synthesis silver nanoparticles (AgNPs) from Pulicaria
      undulata on the amyloid formation in alpha-lactalbumin and the chaperon action of
      alpha-casein.
AB  - The formation and deposition of protein fibrillar aggregates in the tissues is
      associated with several neurodegenerative diseases such as Alzheimer's and
      Parkinson's disease. Molecular chaperones are a family of proteins that are
      believed to have the ability to inhibit protein aggregation. The present study
      examines the effect of different concentrations of green synthesis silver
      nanoparticles (AgNPs) from Pulicaria undulata L. on the aggregation of alpha
      lactalbumin (alpha-LA) and the chaperone action of alphas-casein. The effects of
      the AgNPs were determined by measuring light scattering absorption, fluorescence
      (ThT assay, intrinsic fluorescence assay and ANS binding assay), TEM, CD
      spectroscopy and SDS-PAGE. The results showed that AgNPs have the ability to
      prevent the aggregation of alpha-LA in a concentration-dependent manner. In fact,
      by increasing the concentration of AgNPs within a specified range, the adsorption
      and interaction between AgNPs and protein have increased and protein
      conformational changes and self-association decreased, thus amyloid aggregation
      is prevented. Our results also showed that alpha-casein effectively prevented the
      aggregation of the alpha-lactalbumin which increased in the presence of the
      AgNPs. Standard experimental results, however, proved that nanoparticles had no
      effect on the structure and hence the chaperone ability of alpha-casein. Our
      findings showed that AgNPs can prevent protein aggregation and have no effect on
      the chaperone ability of alphas-casein. In the main, results of this study show
      that biosynthesized AgNPs mediated by Pulicaria undulata L. has the capability in
      inhibiting amyloid fibril formation and thus could be consider as a therapeutic
      agent in the treatment of amyloidosis disorders.

PMID- 29225182
TI  - Hydrophobization of cashew gum by acetylation mechanism and amphotericin B
      encapsulation.
AB  - Cashew gum (GC) is a polysaccharide whose structural modification has the
      potential to extend its applications on varied fields such as to the formation of
      self-organized nanoparticulated systems. In this work, a 23 factorial design was
      carried out, aiming at evaluation of the influence of the reactional parameters
      of an acetylation reaction on the final properties of cashew gum. The effects of
      temperature, reaction time and amount of acetylating agent on the reaction yield
      and degree of GC acetylation were investigated. Data obtained revealed that the
      aforementioned parameters influenced both yield and degree of acetylation.
      Statistical analysis showed that the different derivatives had their variables
      influenced mainly by temperature and interaction effect between the factors time
      and quantity of acetylating agent. Acetylated derivatives were obtained with
      yield higher than 90% and degrees of acetylation above 2.42. Data on the
      formation of self-organized systems, revealed particle sizes in the range 190
      300nm, where smaller particle sizes were obtained for derivatives with
      acetylation degrees lower than 1.5. Release profiles of Amphotericin-B
      incorporated in derivative nanoparticles, yielded 70% encapsulation efficiency
      and long release profiles, corroborating their potential application to delivery
      of hydrophobic active principles.

PMID- 29225183
TI  - Ca2+ mediates axotomy-induced necrosis and apoptosis of satellite glial cells
      remote from the transection site in the isolated crayfish mechanoreceptor.
AB  - Severe nerve injury such as axotomy induces neuron degeneration and death of
      surrounding glial cells. Using a crayfish stretch receptor that consists of a
      single mechanoreceptor neuron enveloped by satellite glia, we showed that axotomy
      not only mechanically injures glial cells at the transection location, but also
      induces necrosis or apoptosis of satellite glial cells remote from the
      transection site. We studied Ca2+role in spontaneous or axotomy-induced death of
      remote glial cells. Stretch receptors were isolated using the original technique
      that kept the neuron connected to the ventral cord ganglion (control
      preparations). Using Ca2+-sensitive fluorescence probe fluo-4, we showed Ca2+
      accumulation in neuronal perikarion and glial envelope. Ca2+ gradually
      accumulated in glial cells after axotomy. In saline with triple Ca2+
      concentration the axotomy-induced apoptosis of glial cells increased, but
      spontaneous or axotomy-induced necrosis was unexpectedly reduced. Saline with
      1/3[Ca2+], oppositely, enhanced glial necrosis. Application of ionomycin, CdCl2,
      thapsigargin, and ryanodine showed the involvement of Ca2+ influx through ionic
      channels in the plasma membrane, inhibition of endoplasmic reticulum Ca2+-ATPase,
      and Ca2+ release from endoplasmic reticulum through ryanodine receptors in
      axotomy-induced glial necrosis. Apoptosis of glial cells surrounding axotomized
      neurons was promoted by ionomycin and thapsigargin. Possibly, other Ca2+ sources
      such as penetration through the plasma membrane contributed to axotomy-induced
      apoptosis and necrosis of remote glial cells. Thus, modulating different pathways
      that maintain calcium homeostasis, one can modulate axotomy-induced death of
      glial cells remote from the transection site.

PMID- 29225184
TI  - Control of polarization and tumoricidal activity of macrophages by multicellular
      spheroid formation.
AB  - Immune cell-based therapy is a promising approach for cancer immunotherapy.
      Macrophages can be used for this purpose if their tumoricidal activity and
      viability are properly controlled. In the present study, we aimed to enhance
      these properties of macrophages by constructing uniformly sized multicellular
      spheroids. Mouse macrophage-like J774.1 cells were selected as model macrophages,
      and poly(N-isopropylacrylamide)-coated polydimethylsiloxane-based microwell
      plates with an approximate diameter of 750MUm were used to prepare J774.1
      spheroids. J774.1 spheroids were successfully generated, and the viability of
      cells in the spheroids was over 95%. J774.1 spheroids showed higher mRNA
      expression of induced nitric oxide synthase, a marker of M1-type activated
      macrophages, than monolayered J774.1 cells. The production of reactive oxygen
      species was also high in J774.1 spheroids, suggesting the existence of hypoxic
      regions in the spheroids. J774.1 spheroids released more tumor necrosis factor
      alpha than monolayered cells upon stimulation with lipopolysaccharide. Moreover,
      J774.1 spheroids in the upper compartment of the Transwell system more
      efficiently inhibited the proliferation of mouse adenocarcinoma colon 26 cells in
      its lower compartment than monolayered J774.1 cells did. These results indicate
      that spheroid formation can be used to increase the tumoricidal activity of
      macrophages for use in cell-based cancer immunotherapy.

PMID- 29225185
TI  - Reactive oxygen species metabolism and plant-fungal interactions.
AB  - Fungal interactions with plants can involve specific morphogenetic developments
      to access host cells, the suppression of plant defenses, and the establishment of
      a feeding lifestyle that nourishes the colonizer often-but not always-at the
      expense of the host. Reactive oxygen species (ROS) metabolism is central to the
      infection process, and the stage-specific production and/or neutralization of ROS
      is critical to the success of the colonization process. ROS metabolism during
      infection is dynamic-sometimes seemingly contradictory-and involves endogenous
      and exogenous sources. Yet, intriguingly, molecular decision-making involved in
      the spatio-temporal control of ROS metabolism is largely unknown. When also
      considering that ROS demands are similar between pathogenic and beneficial fungal
      plant interactions despite the different outcomes, the intention of our review is
      to synthesize what is known about ROS metabolism and highlight knowledge gaps
      that could be hindering the discovery of novel means to mediate beneficial plant
      microbe interactions at the expense of harmful plant-microbe interactions.

PMID- 29225186
TI  - Hinokitiol inhibits compound action potentials in the frog sciatic nerve.
AB  - Hinokitiol (beta-thujaplicin) is a natural tropolone derivative contained in
      Chamaecyparis taiwanensis that has various actions including anti-inflammatory
      activities. Various plant-derived compounds inhibit compound action potentials
      (CAPs) in a manner dependent on the chemical structure of the compounds; however,
      the effects of hinokitiol on nerve conduction have not been examined. To
      determine whether hinokitiol inhibits CAPs and, if so, the chemical structure of
      hinokitiol that is important in this inhibition, we examined the effects of
      hinokitiol and its related compounds on fast-conducting CAPs using the frog
      sciatic nerve and the air-gap method. Hinokitiol concentration-dependently
      reduced the peak amplitude of CAPs with a half-maximal inhibitory concentration
      (IC50) value of 0.54mM. A stereoisomer of hinokitiol, gamma-thujaplicin, also
      inhibited CAPs. Although hinokitiol has hydroxyl, carbonyl and isopropyl groups,
      all of which are bound to its seven-membered ring, tropolone, which lacks the
      isopropyl group, had no effects on CAPs. Moreover, CAPs were unaffected by kojic
      acid, which lacks an isopropyl group, and also by guaiazulene, which has an
      isopropyl group but not carbonyl or hydroxyl groups. Biosol and 4
      isopropylphenol, which have isopropyl and hydroxyl groups bound to their six
      membered ring, reduced CAP peak amplitudes. This 4-isopropylphenol's activity was
      more effective than 4-isopropylcyclohexanol and phenol, and less effective than 4
      tert-butylphenol and 4-tert-amylphenol; isopropylbenzene had no effects on CAPs.
      These results indicate that hinokitiol inhibits frog CAPs, possibly through
      interaction involving its isopropyl, carbonyl and hydroxyl groups. Hinokitiol,
      therefore, has an ability to inhibit nerve conduction, which contributes partly
      to the pharmacological actions of hinokitiol.

PMID- 29225187
TI  - Prostaglandin D2 generation from human lung mast cells is catalysed exclusively
      by cyclooxygenase-1.
AB  - Mast cells are an exceptionally rich source of prostaglandin D2 (PGD2). PGD2 is
      pro-inflammatory and can cause bronchoconstriction. The enzyme cyclooxygenase
      (COX) is central to the generation of prostanoids such as PGD2. Non-steroidal
      anti-inflammatory drugs (NSAIDs) inhibit COX. COX exists as two isoforms, COX-1
      and COX-2. The principal aim of this study was to establish whether COX-1 and/or
      COX-2 mediates PGD2 generation from human lung mast cells. Mast cells were
      isolated from human lung tissue and purified by flotation over Percoll and
      immunomagnetic bead separations. The cells were activated with anti-IgE or Stem
      Cell Factor (SCF). The generation of PGD2 was determined by ELISA. The effects of
      NSAIDs (aspirin, ibuprofen, diclofenac, naproxen, indomethacin), COX-1 selective
      (FR122047), and COX-2 selective (celecoxib) inhibitors on PGD2 generation were
      determined. The expression of COX-1 and COX-2 in mast cells was determined by
      Western blotting. All the NSAIDs tested abrogated stimulated PGD2 generation from
      mast cells except aspirin which was only weakly effective. FR122047 was an
      effective inhibitor of PGD2 generation (EC50 ~25nM) from mast cells whereas
      celecoxib was ineffective. Immunoblotting indicated that COX-1 was strongly
      expressed in all mast cell preparations while COX-2 expression was weak. No
      induction of COX-2 was observed following activation of mast cells. These
      findings indicate that COX-1 is the principal isoform involved in generating PGD2
      from human lung mast cells. These studies provide insight into the potential
      behaviour of NSAIDs in the context of respiratory diseases.

PMID- 29225188
TI  - Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload
      via regulating the crosstalk of Nrf2/ARE and TGF-beta/ smads pathways in rat
      heart.
AB  - Left ventricular hypertrophy is more commonly associated with hemodynamic
      overload imposed by hypertension or volume overload. Transforming growth factor
      beta (TGF-beta) is involved in the cardiac hypertrophy and fibrosis of the left
      ventricle. The fact that TGF-beta1 and the nuclear factor erythroid 2-related
      factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests
      that these two factors may virtually impact on their signaling pathways. In this
      research, 40 rats were divided into sham group, model group, rosuvastatin low and
      high dose group. Rat models were established by incomplete constriction of
      abdominal aorta. After five weeks treatment, blood pressure, heart mass index
      (HMI), hemodynamic parameters and the average diameter of myocardium cell and
      collagen volume fraction (CVF) improved significantly in rosuvastatin groups,
      compared with the model group. Both rosuvastatin groups, increased in expression
      of Smad7, Nrf2, NAD (P) H dehydrogenase [quinone] 1 (Nqo1) and heme oxygenase
      1(Ho1),and decreased in expression of TGF-betal,Smad3 compared with the model
      group. Results from co-immunoprecipitation and GST pull down showed that Nrf2
      interacts with Smad7. Our results revealed the crosstalk between TGF-beta1/Smads
      and Nrf2/ antioxidant response elements (ARE) pathways in myocardial remodeling
      through the interaction between Smad7 and Nrf2. Rosuvastatin can improve cardiac
      function and hypertrophy by regulating the crosstalk of the two signaling
      pathways.

PMID- 29225189
TI  - Luteolin attenuates airway inflammation by inducing the transition of CD4+CD25-
      to CD4+CD25+ regulatory T cells.
AB  - Regulatory T cells play an important role in autoimmunity and have been shown to
      exert anti-inflammatory effects in allergic asthma. Mouse model of airway
      inflammation was used to examine the suppressive activity of luteolin-induced
      CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were
      sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various
      biological processes were examined, including airway eosinophilia; mucus
      hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and
      chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper
      responsiveness (AHR). Luteolin significantly inhibited OVA-induced increase in
      immune cell and eosinophil counts as well as IL-4, IL-5, IL-13, and eotaxin
      levels in bronchoalveolar lavage fluid (BAL Fluid). Luteolin and cyclosporine A
      (CsA) which was a positive control also substantially reduced OVA-specific IgE
      levels, eotaxin 2 levels, and CCR3 expression in BAL Fluid. In contrast, luteolin
      significantly increased IL-10 and IFN-gamma protein levels, as well as IL-10 and
      TGF-beta1 mRNA expression in the lung. In vitro studies showed that the number of
      luteolin-induced CD4+CD25+ Treg (iTreg) cells was higher, with elevated levels of
      TGF-beta1 and foxp3 mRNA expression in lungs tissue. Transfer of iTreg cells into
      OVA-sensitized mice reduced AHR, eosinophil recruitment, eotaxin, IgE, and Th2
      cytokine expressions, and increased IFN-gamma production in BAL Fluid after
      allergen challenge. Furthermore, adoptive transfer of iTreg cells prevented
      disease in a CD25-depleted mouse asthma model. Luteolin via induction of foxp3
      and CD4+CD25+ Treg cells may represent a new strategy in the development of
      therapies for managing asthma.

PMID- 29225190
TI  - Scopolamine-induced passive avoidance memory retrieval deficit is accompanied
      with hippocampal MMP2, MMP-9 and MAPKs alteration.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive loss of memory and cognitive deficit. The observed amnesia in the
      early stages of AD is suggested to be a retrieval problem, rather than encoding
      and consolidation deficit. According to the cholinergic hypothesis of AD,
      scopolamine is used to induce an animal model of amnesia. Howbeit the effect of
      scopolamine on memory retrieval is contradictory. This study aimed to assess the
      effect of scopolamine on passive avoidance memory retrieval. Additionally
      according to the reported changes of MMP-2, MMP-9 and MAPKs (ERK, P38 and JNK) in
      AD pathology the hippocampal contents of these proteins were determined. Male
      NMRI mice weighing 20-25g were trained in passive avoidance apparatus. The drug
      or its vehicle was injected 24h after training (30min before retention test). The
      hippocampal tissue was isolated and western blot analysis was done for MMP-2, MMP
      9 and MAPKs (ERK, P38 and JNK). The results indicated that scopolamine (1mg/kg)
      disrupts passive avoidance memory retrieval. This scopolamine treatment resulted
      in hippocampal MMP-2 and MMP-9 decline while increased MAPKs in the hippocampus.
      These results suggest that cholinergic system has an important role in learnt
      memory retrieval. It might also suggest the positive role of MMP-2 and MMP-9 in
      this phase of memory while propose that MAPKs affect negatively the reactivation
      of memory which is compatible with MAPKs activation in AD.

PMID- 29225191
TI  - The comprehensive electrophysiological study of curcuminoids on delayed-rectifier
      K+ currents in insulin-secreting cells.
AB  - Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic
      beta-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and
      bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents
      inherently in insulin-secreting cells remains largely unclear. The effects of CUR
      and other structurally similar curcuminoids on ion currents in rat insulin
      secreting (INS-1) insulinoma cells were therefore investigated in this study. The
      effects of these compounds on ionic currents and membrane potential were studied
      by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K+
      current (IK(DR)) in a time-, state- and concentration-dependent manner in these
      cells and the inhibition was not reversed by diazoxide, nicorandil or
      chlorotoxin. The value of dissociation constant for CUR-induced suppression of
      IK(DR) in INS-1 cells was 1.26MUM. Despite the inability of CUR to alter the
      activation rate of IK(DR), it accelerated current inactivation elicited by
      membrane depolarization. Increasing CUR concentrations shifted the inactivation
      curve of IK(DR) to hyperpolarized potential and slowed the recovery of IK(DR)
      inactivation. CUR, DMC, and BDMC all exerted depressant actions on IK(DR)
      amplitude to a similar magnitude, although DMC and BDMC did not increase current
      inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated
      Na+ current. CUR, DMC and BDMC depolarized the resting potential and increased
      firing frequency of action potentials. The CUR-mediated decrease of IK(DR) and
      the increase of current inactivation also occurred in betaTC-6 INS-1 cells. Taken
      these results together, these effects may be one of the possible mechanisms
      contributing their insulin-releasing effect.

PMID- 29225192
TI  - Effects of the new psychoactive substances diclofensine, diphenidine, and
      methoxphenidine on monoaminergic systems.
AB  - Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances
      (NPSs) that recently appeared on the illicit drug market. Pharmacological
      profiling of such newly emerged drugs is crucial for a better understanding of
      their psychotropic effects and toxicity. We therefore investigated the potential
      of these NPSs to inhibit the norepinephrine, dopamine, and serotonin transporters
      in human embryonic kidney cells stably transfected with the respective
      transporters. In addition, we determined monoamine transporter and receptor
      affinities for the substances. Diclofensine potently bound to the monoamine
      transporters in the submicromolar range and had similar inhibition potential for
      all three transporters in the range of 2.5-4.8MUM. Moreover, diclofensine bound
      to adrenergic, dopamine, serotonin, and trace amine-associated receptors.
      Diphenidine was an equipotent inhibitor of the norepinephrine and dopamine
      transporters in the low micromolar range and a very weak inhibitor of the
      serotonin transporter. Besides binding to transporters, diphenidine bound to
      adrenergic alpha1A and alpha2A receptors and serotonin 5-hydroxytryptamine 1A (5
      HT1A) and 5-HT2A receptors in the range of 4-11MUM. Methoxphenidine bound to all
      transporters, but considerable inhibition (IC50 < 10MUM) was observed only for
      the norepinephrine transporter. Moreover, methoxphenidine bound to adrenergic
      alpha2A and serotonin 5-HT2A and 5-HT2C receptors in the range of 2.5-8.2MUM.
      None of the test drugs mediated substrate-type efflux of monoamines. These data
      demonstrate that the monoamine transporter inhibition and receptor interactions
      most likely mediate the psychoactive effects of diclofensine and possibly play a
      contributory role for diphenidine and methoxphenidine.

PMID- 29225194
TI  - 57R2A, a newly established monoclonal antibody against mouse GPR56, marks long
      term repopulating hematopoietic stem cells.
AB  - GPR56 molecule, a G-protein-coupled receptor, was suggested to be expressed in
      mouse hematopoietic stem cells (HSCs) by gene expression analyses. However,
      little is known about the cell surface expression of GPR56 protein in mouse HSCs
      due to the absence of an appropriate monoclonal antibody against GPR56 for flow
      cytometry analyses. In the present study, we established a novel monoclonal
      antibody against mouse GPR56 (57R2A) to examine the expression and distribution
      of GPR56 protein in HSCs. A flow cytometry analysis using 57R2A showed that GPR56
      was highly expressed in the CD34-, c-Kit+, Sca-1+, lineage-negative (Lin-)
      fraction, which are highly enriched with HSCs. The competitive long-term
      repopulation (LTR) assay showed that LTR cells were included only within the
      GPR56+ fraction (<=15%) of bone marrow mononuclear cells (BMMNCs), but not within
      the remaining GPR56- fraction (85%), suggesting that all HSCs express GPR56
      protein on their surface. Furthermore, we showed that double staining of BMMNCs
      with only 57R2A and AMM2 (monoclonal antibody against the HSC marker MPL) enabled
      enrichment of all LTR cells in the double-positive fraction (0.8% of BMMNCs),
      within which the LTR potency was consistent with the expression of both GPR56 and
      MPL. In conclusion, these findings for 57R2A suggest that all HSCs in mouse
      BMMNCs express GPR56 protein on their surface and that GPR56 is a positive marker
      for HSCs.

PMID- 29225193
TI  - Synthesis and in vitro characterization of a P2X7 radioligand [123I]TZ6019 and
      its response to neuroinflammation in a mouse model of Alzheimer disease.
AB  - The purinergic receptor P2X ligand-gated ion channel 7 (P2X7 receptor) is a
      promising imaging target to detect neuroinflammation. Herein, we report
      development of a potent iodinated radiotracer for P2X7 receptor, [123I]TZ6019.
      The radiosynthesis of [123I]TZ6019 was accomplished by allylic-tin precursor
      iodination using [123I]NaI with good radiochemical yield of 85% and high
      radiochemical purity of > 99%. Human embryonic kidney 293 (HEK-293) cell line
      stably transfected with the human P2X7 receptor was used to characterize the
      binding affinity of TZ6019 by fluorescence, radioactive competitive, and
      saturation binding assays. A radioligand competitive binding assay with
      [123I]TZ6019 demonstrated that the nonradioactive compound TZ6019 has an IC50
      value of 9.49 +/- 1.4nM, and the known P2X7 receptor compound GSK1482160 has an
      IC50 value of 4.30 +/- 0.86nM, consistent with previous reports. The radioligand
      saturation binding assay and competitive assay revealed that [123I]TZ6019
      specifically bound to the human P2X7 receptor with high affinity (Ki = 6.3 +/-
      0.9nM). In vitro autoradiography quantification with brain slices collected from
      9-month old P301S tau transgenic mice along with wild type controls, revealed
      higher binding of [123I]TZ6019 (35% increase) in the brain of P301S transgenic
      mice (n = 3, p = 0.04) compared to wild type controls. The immunofluorescence
      microscopy confirmed that expression of P2X7 receptor was colocalized with
      astrocytes in the tauopathy P301S transgenic mice. [123I]TZ6019 has specific
      binding for P2X7 receptor and has great potential to be a radiotracer for
      screening new compounds and quantifying expression of P2X7 receptor in
      neuroinflammation related diseases.

PMID- 29225195
TI  - Strengthening integration of clinical and public health systems to prevent
      maternal-child obesity in the First 1,000Days: A Collective Impact approach.
AB  - INTRODUCTION: Obesity interventions may be most effective if they begin in the
      earliest stages of life, support changes across family, clinical, and public
      health systems, and address socio-contextual factors. METHODS: The First 1000Days
      is a systematic program starting in early pregnancy lasting through the first
      24months of infancy to prevent obesity among low-income mother-infant pairs in
      three community health centers in Massachusetts. The program uses a Collective
      Impact approach to create the infrastructure for sustained, system-wide changes
      for obesity prevention across early life clinical and public health services,
      including Obstetrics, Pediatrics, Adult Medicine, Behavioral Health, Nutrition,
      Community Health, the Women, Infants and Children (WIC) program, and the
      Maternal, Infant and Childhood Home Visiting program. Program components include
      1) staff and provider training; 2) enhanced gestational weight gain and infant
      overweight tracking; 3) universal screening of adverse health behaviors and socio
      contextual factors; 4) universal patient navigation to support individual
      behavior change and social needs, while strengthening integration of clinical and
      public health services; 5) individualized health coaching for mother-infant pairs
      at high risk of obesity; and 6) educational materials to support behavior change.
      RESULTS: A quasi-experimental evaluation design will examine changes, between
      2015 and 2019, in gestational weight gain and prevalence of infant overweight
      from 0 to 24months of age. CONCLUSIONS: The First 1000Days program will examine
      the effectiveness of an early life obesity prevention program for mother-infant
      pairs. If successful, the program could provide a model for chronic disease
      prevention and health promotion among vulnerable families starting in early life.

PMID- 29225196
TI  - In the Neighborhood of 18 Million: Estimating How Many People Live Near Oil and
      Gas Wells.

PMID- 29225197
TI  - Percutaneous transgastrostomic interventional radiology-operated endoscopy
      facilitates foreign body removal using rigid endobronchial forceps.
AB  - Retained foreign bodies within the stomach and proximal small bowel may be
      problematic in patients with prior cerebrovascular injury or head, neck and
      esophageal malignancy, given the increased vulnerability of this patient
      population to complications from aspiration and increased difficulty of
      esophagogastroduodenoscopy in cases of tumoral obstruction. This article presents
      an alternative method for foreign body retrieval through an existing gastrostomy
      tract, which offers the benefits of fast procedure times, reduction in radiation
      dose and fluoroscopy time, and allows for safer retrieval of foreign bodies by
      using direct visualization. This technique may be performed entirely by
      interventional radiologists.

PMID- 29225198
TI  - Perspective in optimization of stem cell therapies for heart regeneration.
AB  - There is a variety of mechanisms(s) factor(s) that may influence stem cell
      therapies for heart regeneration. Among the best candidates for stem cell source
      are: mesenchymal stem cells (also those isolated from adipose tissue), cardiac
      cell progenitors (CPC) and descendants of iPSC cells. iPSC/s can be potentially
      beneficial although their pluripotent induction has been still in question due
      to: low propagation efficacy, danger of genomic integration/instability,
      biological risk of current vector system teratoma formation etc. which have been
      discussed in this review. Optimization protocols are required in order to enhance
      stem cells resistance to pathological conditions that they may encounter in
      pathological organ and to increase their retention. Combination between gene
      transfer and stem cell therapy is now more often used in pre-clinical studies
      with the prospect of subsequent clinical trials. Complementary substances have
      been contemplated to support stem cell viability (mainly anti-inflammatory and
      anti- apoptotic agents), which have been tested in animal models with promising
      results. Integration of nanotechnology both for efficient stem cell imaging as
      well as with the aim to provide cell supporting scaffolds seem to be inevitable
      for further development of cellular therapies. The whole organ (heart)
      reconstruction as well as biodegradable scaffolds and scaffold-free cell sheets
      have been also outlined.

PMID- 29225199
TI  - Structure of bacterial chromosome: An analysis of DNA-protein interactions in
      vivo.
AB  - According to recent reports, bacterial chromosomes exhibit a hierarchical
      organization. The number of proteins that bind DNA are responsible for local and
      global organization of the DNA ensuring proper chromosome compaction. Advanced
      molecular biology techniques combined with high-throughput DNA sequencing methods
      allow a precise analysis of bacterial chromosome structures on a local and global
      scale. Methods such as in vivo footprinting and ChIP-seq allow to map binding
      sites of analyzed proteins in certain chromosomal regions or along the whole
      chromosome while analysis of the spatial interactions on global scale could be
      performed by 3C techniques. Additional insight into complex structures created by
      chromosome-organizing proteins is provided by high-resolution fluorescence
      microscopy techniques.

PMID- 29225200
TI  - SUMO proteases as potential targets for cancer therapy.
AB  - Sumoylation is one of the post-translational modifications of proteins,
      responsible for the regulation of many cellular processes, such as DNA
      replication and repair, transcription, signal transduction and nuclear transport.
      During sumoylation, SUMO proteins are covalently attached to the epsilon-amino
      group of lysine in target proteins via an enzymatic cascade that requires the
      sequential action of E1, E2 and E3 enzymes. An important aspect of sumoylation is
      its reversibility, which involves SUMO-specific proteases called SENPs. SENPs
      (sentrin/SUMO-specific proteases) catalyze the deconjugation of SUMO proteins
      using their isopeptidase activity. These enzymes participate through hydrolase
      activity in the reaction of SUMO protein maturation, which involves the removal
      of a short fragment on the C-terminus of SUMO inactive form and exposure two
      glycine residues. SENPs are important for maintaining the balance between
      sumoylated and desumoylated proteins required for normal cellular physiology. Six
      SENP isoforms (SENP1, SENP2, SENP3, SENP5, SENP6 and SENP7) have been identified
      in mammals. These SENPs can be divided into three subfamilies based on their
      sequence homology, substrate specificity and subcellular localization. Results of
      studies indicate the role of SUMO proteases in the development of human diseases
      including cancer, suggesting that these proteins may be attractive targets for
      new drugs.

PMID- 29225201
TI  - 3-Bromopyruvate as a potential pharmaceutical in the light of experimental data.
AB  - 3-Bromopyruvate (3-BrPA) is an halogenated analogue of pyruvic acid known for
      over four decades as an alkylating agent reacting with thiol groups of many
      proteins. It enters animal cells like a lactate: via monocarboxylic acid
      transporters. Increasing interest in this compound, in recent times, is mainly
      due to hopes associated with its anticancer action. It is based on the impairment
      of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis
      pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase,
      phosphoglycerate kinase) and the oxidative phosphorylation (succinate
      dehydrogenase). Two cases of clinical application of this compound in the
      treatment of advanced cancers were reported. By using 3-BrPA, rheumatoid
      arthritis in SKG mice has been reduced. This compound has also antiparasitic
      activity: lowers cell viability of Trypanosoma brucei, decreases intracellular
      proliferation of Toxoplasma gondii and reduces the metabolic activity of
      Schistosoma mansoni. It also has antifungal properties; particularly it acts
      strongly on Cryptococcus neoformans, as well as Saccharomyces cerevisiae. An
      inhibitory effect on bacterial enzymes was also described on: isocitrate lyase
      from Escherichia coli, Mycobacterium tuberculosis, Pseudomonas indigofera and 2
      methylisocitrate lyase, succinate dehydrogenase and acetohydroxylic acid synthase
      from Escherichia coli. Wherever undesirable (cancer, parasitic) cells differ from
      normal by more intense glycolysis and higher energy needs, there is a good chance
      of successful 3-BrPA use. However, this compound acts on all cells and it,
      therefore, seems that its future as a pharmaceutical is dependent upon the
      development of appropriate methods for its effective and safe application.

PMID- 29225202
TI  - Epigenetic modifications: An important mechanism in diabetic disturbances.
AB  - In the search for explanations of diabetes pathomechanisms, especially the
      development of its vascular complications (micro- and macrovascular ), although
      current, good metabolic control of diabetes, attention was drawn to the role of
      epigenetic inheritance associated with epigenetic modifications of histone
      proteins and DNA in hyperglycemia conditions. This study showed the significant
      role of DNA methylation and histone epigenetic modifications (a different nature
      and a different degree) in the transmission of information that is not connected
      with gene inheritance but concerns the persistent changes induced by
      hyperglycemia..Attention was paid to the role of DNA methylation of pancreatic
      cells in the pathogenesis of type 1 diabetes, but also type 2. The important role
      of DNA methylation changes in a so-called intrauterine growth restriction (IUGR)
      as reason of subsequent development of diabetes was particularly emphasized. In
      the pathogenesis of type 2 diabetes and its complications, especially
      microvascular complications, the greatest share and importance of epigenetic
      modifications on mitochondrial DNA metylation are the most important. The
      multidirectionality Complicaand complexity of epigenetic modifications of histone
      proteins indicate their importance in the development of diabetic disturbances.
      An especially important role is attributed to methylation and acetylation of
      histone proteins, in particular on arginine and lysine, whose changes occur most
      frequently. Moreover, epigenetic modifications of the enzymes, especially
      methylases, responsible for these processes are the underlying. It has been
      indicated that the identification of epigenetic differences within the DNA or
      histone proteins may be a useful prognostic biomarker of susceptibility to the
      disease development in the future. Moreover, they may become a potential target
      for future therapeutic interventions for clinical disorders in diabetes.

PMID- 29225203
TI  - Stigmatization in dermatology with a special focus on psoriatic patients.
AB  - A stigma is currently defined as a discrediting mark, biological or social, that
      sets a person off from others and disrupts interactions with them. People who
      differ from social norms in some respect are often negatively labeled. A number
      of medical conditions are recognized at present as stigmatizing their sufferers
      and certain skin diseases are among them. The article aimed to analyze the
      current understanding about stigmatization among dermatological patients,
      especially those with psoriasis. We performed our search on PubMed up to November
      2016 and utilized combinations of key phrases containing such words as
      stigmatization, skin, dermatology, names of various skin conditions (psoriasis,
      vitiligo, acne, etc.). Following a precise selection process, 58 articles
      remained. Stigmatization seems to be a common and important problem in
      dermatology. Psoriasis appears as the most frequently studied skin disease (37.2%
      of articles). It was followed by vitiligo (13.7%) and leprosy (8.6%). Mainly, the
      visibility of skin lesions as well as cultural factors contribute to the feeling
      of stigmatization. There is a need for more research in the field of
      stigmatization in dermatological conditions and an urgent need for the creation
      of special anti-stigmatization program/programs for patients suffering from
      dermatoses.

PMID- 29225204
TI  - New theories of relativistic hydrodynamics in the LHC era.
AB  - The success of relativistic hydrodynamics as an essential part of the
      phenomenological description of heavy-ion collisions at RHIC and the LHC has
      motivated a significant body of theoretical work concerning its fundamental
      aspects. Our review presents these developments from the perspective of the
      underlying microscopic physics, using the language of quantum field theory,
      relativistic kinetic theory, and holography. We discuss the gradient expansion,
      the phenomenon of hydrodynamization, as well as several models of hydrodynamic
      evolution equations, highlighting the interplay between collective long-lived and
      transient modes in relativistic matter. Our aim to provide a unified presentation
      of this vast subject-which is naturally expressed in diverse mathematical
      languages-has also led us to include several new results on the large-order
      behaviour of the hydrodynamic gradient expansion.

PMID- 29225205
TI  - Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis
      in adolescent rat.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and
      consumer products, which has resulted in widespread human exposure. Limited
      studies have suggested that exposure to DEHP may affect thyroid function, but
      little is known about the effect and mechanisms of DEHP exposure on the
      hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to
      elucidate the potential mechanisms in which DEHP disrupts the function of the
      HPTA. Wistar rats were administered DEHP by gavage at 0, 5, 50, and 500 mg/kg/day
      for 28 days and then sacrificed within 24 h following the last dose. Hormones of
      HPTA was quantified with radioimmunoassay and enzyme-linked immunosorbent assay,
      protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid
      stimulating hormone receptor (TSHR) were analyzed by Western blot and
      immunohistochemistry, expression levels of TRHR and TSHR mRNA were measured by
      quantitative real-time PCR. Rats treated with DEHP resulted in increased
      bodyweight, on the HPTA, down-regulated the protein levels of TRH in the
      hypothalamus, up-regulated the protein and mRNA levels of TRHR in the pituitary,
      down-regulated mRNA expression of TSHR in the thyroid, while the difference of
      TSH in various dose groups was not statistically significant and T3, T4, FT3, FT4
      levels in serum were decreased compared with control. DEHP could interfere with
      the balance of HPTA of adolescent rats, and increase the body weight, down
      regulate the homeostasis of thyroid related hormones and receptors expression
      levels.

PMID- 29225206
TI  - Prevalence of central fatness in 1992-1994: 40% of Japanese boys 6-17 years.
AB  - Obesity in children is a serious public health problem in Japan. However, the
      prevalence of central fatness has not been well determined in Japanese youth. We
      studied the relationship between body mass index (BMI) and waist circumference
      (WC) using line of equality analysis in 5,787 boys and 4,639 girls aged 6 to 17
      years who participated in the 1992-1994 national survey on body sizes. WC was
      measured at the level of maximum waist narrowing in girls (WC1) and at the level
      of the top of iliac crest in boys (WC2). Using the 1978-1981 national survey data
      as baseline reference, excess fatness was defined as measurements exceeding the
      90th centile in WC or in BMI. Among boys, 2,466 (42.6%) had WC2 >90th centile and
      1,029 (17.8%) BMI >90th centile; whereas among girls, 895 (19.3%) had WC1 >90th
      centile and 673 (14.5%) BMI >90th centile. WC2-standard deviation scores (SDS)
      exceeded BMI-SDS in 5,060 (87.4%) boys and WC1-SDS exceeded BMI-SDS in 3,168
      (68.3%) girls, respectively. Our results suggested a much higher prevalence of
      central fatness than generally recognized for Japanese children and adolescents,
      in particular, in Japanese boys.

PMID- 29225207
TI  - Parathyroid carcinoma occurred in two glands in multiple endocrine neoplasia 1: a
      report on a rare case.
AB  - Primary hyperparathyroidism is the most common hormonal manifestation associated
      with multiple endocrine neoplasia 1 (MEN1). It is generally caused by parathyroid
      hyperplasia, and parathyroid carcinoma is rare. Here, we report a case of MEN1
      with parathyroid carcinoma in two parathyroid glands causing primary
      hyperparathyroidism. A 40-year-old man with primary hyperparathyroidism due to
      MEN1 underwent a total parathyroidectomy. His corrected calcium and intact PTH (i
      PTH) serum levels were 10.8 mg/dL and 203 pg/mL, respectively. Although three
      glands were successfully removed, the left upper parathyroid gland could not be
      detected. Since the right lower parathyroid lesion had invaded into the thyroid,
      right lobectomy was performed. A portion of the left lower parathyroid tissue was
      transplanted into his forearm. The histological findings of the left lower and
      the right upper parathyroid glands were consistent with hyperplasia while that of
      the right lower parathyroid gland was parathyroid carcinoma. Since the post
      surgical i-PTH levels remained high, the intrathyroidal lesion of the left lobe,
      which was initally diagnosed as an adenomatous nodule, was suspected to contain
      parathyroid tumor. A fine needle aspiration of the tumor revealed a high
      concentration of i-PTH. One week after the first surgery, a left thyroid
      lobectomy was performed. The pathological diagnosis of the tumor was parathyroid
      carcinoma. After the surgery, calcium and i-PTH levels were normal. Although it
      is rare, parathyroid carcinoma should be considered as a cause of
      hyperparathyroidism in MEN1 patients. Since it is difficult to diagnose
      parathyroid carcinoma before surgery, intraoperative findings are important for
      the appropriate treatment.

PMID- 29225208
TI  - Dietary Calcium and Serum 25OHD Protect Chinese Women from Type 2 Diabetes.
AB  - The Chinese dietary structure is different from Western and Mediterranean diets.
      This study aimed to assess the association of dietary calcium, serum 25
      hydroxyvitamin D (25OHD), and other macronutrients with type 2 diabetes (T2D) in
      Chinese patients. This case-control study enrolled 605 patients (males, 337;
      females, 268) with T2D and 724 healthy subjects (males, 405; females, 319) at Sir
      Run Run Shaw Hospital from February to April 2014. Dietary calcium, total energy,
      fat to energy ratio, glucose administration, 2-h postprandial blood glucose,
      serum total cholesterol and high density lipoprotein (HDL)-cholesterol, and serum
      25OHD level were assessed. Logistic regression was used to assess the
      associations of various parameters with T2D. Total energy, fat, and the fat-to
      energy ratio were significantly higher in healthy male and female controls than
      in T2D patients (p<0.05). In addition, significant differences were obtained
      between the T2D and control groups in glucose management, 2-h postprandial blood
      glucose, serum total cholesterol, and HDL-cholesterol (all p<0.05).
      Interestingly, statistically significant inverse associations of dietary calcium
      and total energy intake with the risk of T2D were obtained in women; binary
      logistic regression analysis showed diet calcium and serum 25OHD were protecting
      factors against T2D (OR=0.40, p=0.034; OR=0.50, p=0.019). Dietary calcium and
      serum 25OHD may independently protect Chinese women from T2D. These findings
      highlight the importance of vitamin D and calcium in daily diet or supplement in
      the early period of T2D, meanwhile indicators associated with bone metabolism
      should be assessed in clinical nutrition. It is possible that dietary education
      and guidance should be implemented based clinical bone metabolism data.

PMID- 29225210
TI  - Inhibitory role of Munc13-1 in antigen-induced mast cell degranulation.
AB  - Secretory granules (SGs) of mast cells are lysosome-related organelles that
      contain various inflammatory molecules such as histamine, which are stored in the
      cytoplasm. Mast cell degranulation is the regulated exocytosis of SGs in response
      to external stimuli, such as the antigen-mediated cross-linking of the high
      affinity IgE receptor, FcepsilonRI. Upon stimulation, SGs undergo priming to
      become fusion-competent prior to fusing with the plasma membrane, which is
      mediated by Munc13-4, one of the five members of the vesicle-priming Munc13
      protein family. Although Munc13-4 is shown to be crucial for mast cell
      degranulation, the functional involvement of other Munc13 isoform(s) remains
      unknown. Herein, this was investigated using the RBL-2H3 mast cell line. We found
      that Munc13-1 and Munc13-4 are the only Munc13 isoforms that are expressed in the
      RBL-2H3 cells, and Munc13-1 is distributed in the cytoplasm, but highly
      concentrated on the late endosome and/or lysosome. Unexpectedly, antigen-induced
      degranulation was considerably increased by Munc13-1 knockdown, but decreased by
      its overexpression. Further, we found that the hypersecretion phenotype of the
      Munc13-1-knockdown cells was attenuated by simultaneous Munc13-4 knockdown. These
      results suggested that Munc13-1 has an inhibitory role in antigen-induced mast
      cell degranulation, which is performed in a Munc13-4-dependent manner.

PMID- 29225209
TI  - Dapagliflozin Reduces Fat Mass without Affecting Muscle Mass in Type 2 Diabetes.
AB  - AIM: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been
      demonstrated to improve glycemic control and reduce body weight and fat mass in
      type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of
      SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in
      patients with T2DM. METHODS: We prospectively recruited uncontrolled (hemoglobin
      A1c [HbA1c] >7%) Japanese T2DM patients who had a body mass index (BMI) <35
      kg/m2. Patients were treated with dapagliflozin (5 mg/day) or non-SGLT2i
      medicines for six months to improve HbA1c. We investigated changes in body
      composition using bioelectrical impedance analysis and changes in psoas muscle
      mass using abdominal computed tomography (CT). RESULTS: Subjects were 50 T2DM
      patients (72% male) with a mean age of 56.1 years, mean BMI of 27.1 kg/m2 and
      mean HbA1c of 7.9%. HbA1c, body weight, and BMI were significantly decreased in
      both treatment groups, and the HbA1c decrease was not significantly different
      between groups. Dapagliflozin treatment significantly decreased body weight and
      total fat mass without affecting skeletal muscle mass. The absolute change in
      soft lean mass and skeletal muscle mass was not significantly different between
      groups. Dapagliflozin treatment did not significantly decrease psoas muscle
      index, and the absolute change in this index was not significantly different
      between groups. Dapagliflozin therapy also produced a significant increase in CT
      radiation attenuation in the third lumbar paraspinal muscles compared with non
      SGLT2i therapy. CONCLUSIONS: Treatment with dapagliflozin for six months
      significantly improved glycemic control and reduced body weight without reducing
      muscle mass in T2DM patients.

PMID- 29225211
TI  - Changes in FOXO and proinflammatory cytokines in the late stage of immobilized
      fast and slow muscle atrophy.
AB  - The present study aimed to examine the changes in the expression of Forkhead box
      protein O (FOXO) and proinflammatory cytokines in both slow-twitch soleus and
      fast-twitch plantaris muscles following cast immobilization. Male C57BL/6 mice
      were subjected to cast immobilization for 7 and 21 days. Cast immobilization
      increased FOXO3a mRNA and total protein expression in both the soleus and
      plantaris muscles. Although FOXO3a phosphorylation tended to increase in response
      to cast immobilization in both muscles, a significant increase was evident after
      21 days of immobilization only in the soleus muscle. The degree of the response
      of FOXO3a was very different between the soleus and plantaris muscles; however,
      the kinetics of FOXO3a in both muscles were similar. Thus, the regulation of
      muscle atrophy by FOXO might act via a common mechanism in both slow-twitch
      soleus and fast-twitch plantaris muscles. Gene expression of proinflammatory
      cytokines tended to increase in response to cast immobilization, and a
      significant increase was evident after 21 days of immobilization in the soleus
      muscle. However, in the plantaris muscle, proinflammatory cytokine gene
      expression remained unchanged throughout the immobilization period; nevertheless,
      immobilization induced greater reduction in muscle fiber cross-sectional area in
      the plantaris than in the soleus muscle. Thus, these observations indicate that
      regulation of muscle atrophy by proinflammatory cytokines might contribute to
      muscle fiber type-specific mechanisms.

PMID- 29225212
TI  - Iron deficiency induces autophagy and activates Nrf2 signal through modulating
      p62/SQSTM.
AB  - Iron is an essential trace metal in almost all organisms and plays an important
      role in the redox system. We previously reported that iron deficiency activated
      autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling for
      oxidative stress. However, regulatory mechanisms underlying the association
      between autophagy and Nrf2 signaling are unclear. In this study, we found that
      treatment of cells with an iron-specific chelator deferoxamine (DFO) increased
      reactive oxidative species (ROS) production by elevating the expression of
      p47phox and p67phox compared with that in untreated cells. The DFO treatment also
      induced protein aggregation and formed aggresome, which is a cellular response to
      misfolded protein. In addition, DFO treatment upregulated the expression of the
      autophagic gene p62/SQSTM1, which in turn activated intracellular proteolysis
      during autophagy. DFO treatment phosphorylated p62/SQSTM1 (Thr351) to activate
      Nrf2. However, silencing of p62/SQSTM1 followed by DFO treatment attenuated Nrf2
      activation and resulted in the accumulation of carboxyl proteins compared with
      DFO treatment alone. These results indicated that iron deficiency activates Nrf2
      signaling by modulating p62/SQSTM1 during autophagy.

PMID- 29225213
TI  - Fish protein hydrolysate exhibits anti-obesity activity and reduces hypothalamic
      neuropeptide Y and agouti-related protein mRNA expressions in rats.
AB  - Fish protein is a source of animal protein that is consumed worldwide. Although
      it has been reported that the intake of Alaska pollack protein (APP) reduces body
      fat accumulation and increases muscle weight in rats, the mechanisms underlying
      these effects are poorly understood. As a possibility, peptides released from APP
      in the gastrointestinal tract are important to the functions of APP. In the
      present study, we examined the effects of APP hydrolysate digested artificially
      with pepsin and pancreatin on white adipose tissue and skeletal muscle. We found
      that APP hydrolysate group shows significantly lower weight of white adipose
      tissue and higher weight of soleus muscle than the control group. We also found
      that APP hydrolysate group reduces food intake and mRNA expressions of
      neuropeptide Y and agouti-related protein in the hypothalamus compared with the
      control group. These results may imply that APP hydrolysate exhibits anti-obesity
      activity by the reduction of appetite and the enhancement of basal energy
      expenditure by skeletal muscle hypertrophy in rats. The downregulation of
      orexigenic gene by APP hydrolysate in the hypothalamus may contribute to the
      reduction of appetite. These results suggest that the effect of APP on anti
      obesity and muscle hypertrophy may be induced by peptides released from APP in
      the gastrointestinal tract.

PMID- 29225214
TI  - Noradrenergic effects in rat sacral autonomic nucleus using in vitro slice patch
      clamp recordings.
AB  - Noradrenergic modulation has been frequently discussed in the context of neural
      activities that are related to pelvic organs. The sacral preganglionic nucleus
      (SPN) is a spinal nucleus containing parasympathetic preganglionic neurons that
      send fibers to pelvic nerves. In spite of the abundant presence of noradrenergic
      fibers around the SPN, the effects of noradrenaline (NA) remain obscure. To
      explore this issue, NA (50 MUM) was applied to parasympathetic preganglionic
      neurons in the SPN during whole-cell patch clamp recording. The SPN was labeled
      with the retrograde tracer, DiI. These neurons demonstrated two classes of firing
      patterns (delayed and regular) in terms of initiation of firing. Independent of
      these firing patterns, NA induced inward (56%) or outward (32%) currents in
      labeled SPN neurons. Phenylephrine, an alpha1 receptor agonist, induced an inward
      current, and clonidine, an alpha2 receptor agonist, induced an outward current,
      indicating the existence of both alpha1 and alpha2 adrenoreceptors in DiI-labeled
      SPN neurons. NA also modulated synaptic currents according to the firing
      patterns. In delayed firing neurons, NA inhibited both spontaneous excitatory
      post-synaptic currents (sEPSCs) and spontaneous inhibitory post-synaptic currents
      (sIPSCs). Hence, NA facilitated sEPSCs and sIPSCs in about a half of regular
      firing neurons. Bath application of phenylephrine facilitated sEPSCs and sIPSCs,
      and clonidine inhibited them. These results support the hypothesis of multiple
      effects of NA in the SPN, and may suggest functional differences among SPN
      neurons.

PMID- 29225215
TI  - Cognitive impairment with interferon treatment in patients with chronic hepatitis
      C.
AB  - Interferon (IFN) has various side effects, including psychiatric symptoms. Event
      related potentials are used as an electrophysiologic index of cognitive
      disorders. Auditory event-related potentials (P300) are often used in conditions
      in which cognitive ability is affected. In this study, we evaluated the
      association between P300, used to assess cognitive impairment, and
      neuropsychological side effects of IFN treatment in patients with chronic
      hepatitis C. Subjects were 20 patients with chronic hepatitis C; 13 patients were
      treated with peg IFN-alpha2b and ribavirin (riba group), and 7 patients were
      treated with peg IFN-alpha2a (alone group). P300 was performed on all patients
      before treatment and after 1 week, 4 weeks, 2 months, and 3 months of treatment.
      In addition, 10 patients of them completed the self-rating depression scale
      (SDS). P300 latency was significantly prolonged at all points of measurement
      during IFN treatment. No correlation between the change of SDS score and the
      change rate of P300 latency was shown. Six patients with neuropsychological
      symptom had a significantly increased change rate of P300 latency compared with
      patients without neuropsychological symptoms (P < 0.05). Based on P300 findings,
      this study suggests that patients with chronic hepatitis C treated with IFN may
      experience significant cognitive impairment.

PMID- 29225217
TI  - Molecularly Imprinted Materials in Analytical Chemistry.

PMID- 29225218
TI  - A Proposal for Automated Background Removal of Bio-Raman Data.
AB  - The subtraction of background components from observed spectra is essential in
      performing multivariable analysis, frequently applied to Raman spectra of cells.
      The subtraction procedure, however, is manual and time consuming, especially for
      big data. Here, we propose an automated method for removing background
      information from measured spectra of cells, exhibiting the theoretical framework
      and an experimental application.

PMID- 29225216
TI  - Depressive symptoms and risk of absence among workers in a manufacturing company:
      a 12-month follow-up study.
AB  - Depression is a leading cause of reduced work ability and absence due to
      sickness. The objective of this study was to investigate how depressive symptoms
      are prospectively associated with subsequent absence, whether caused by illness
      or accidents, among manufacturing workers. This prospective study was conducted
      on 2,349 male and female employees that underwent a regular health examination at
      a university hospital. Depressive symptoms were measured at baseline using the
      Center for Epidemiologic Studies Depression (CES-D) Scale. Data on self-reported
      absence due to illness and accidents were obtained during a follow up of 1 yr.
      The incidences of sickness absence were 6.0% for men and 17.3% for women. Men and
      women with depressive symptoms (CES-D >=16) were found to have higher odds of
      sickness absence during follow up (men: OR=4.06; 95% CI: 2.32-7.11; women:
      OR=1.75; 95% CI: 1.02-2.98), after adjustment for demographic and occupational
      factors. When depressive symptoms were divided into quartiles, significantly
      higher ORs of sickness absence were observed only among employees with the
      highest quartile of depressive symptoms. The study shows that depressive symptoms
      are a risk factor for future absence due to illness or accidents among
      manufacturing workers.

PMID- 29225219
TI  - Layer Caused an Anisotropic Terahertz Response of a 3D-printed Simulative Shale
      Core.
AB  - Energy demands have motivated the development of shale formations as significant
      unconventional reservoirs. The anisotropy of shales plays a significant role in
      both the mechanical behavior and engineering activities. Alternating layers
      presented in shales affect the propagation of waves, causing anisotropy at
      various frequencies. Simplifying the complicated interior structures of shales is
      conducive to characterize the anisotropic properties. Therefore, simulative shale
      core samples were designed and fabricated using additive manufacturing processes,
      and layer-caused dielectric anisotropy was investigated by terahertz (THz) time
      domain spectroscopy. On the basis of effective medium theory, the change of the
      optical length caused by refraction of rays was discussed and modeled. It is
      believed that the refraction of rays at the interfaces is the source of THz
      propagation anisotropy in the multilayered structure, and the anisotropy degree
      is mainly influenced by the layer thickness as well as the refractive index.

PMID- 29225220
TI  - Amplified Fluorescent Detection of Mercuric Ions by Conjugation of the ThT
      induced G-Quadruplex Based Hybridization Chain Reaction.
AB  - A sensitive fluorescent method for the detection of Hg2+ was developed based on
      triple-helix molecular switch (THMS)-induced hybridization chain reaction (HCR)
      amplification. THMS was composed of a T-rich mercury-specific probe and an
      initiator probe, designed by the Watson-Crick and Hoogsteen base pairings and
      employed as a signal trigger. Two hairpin probes containing the G-quadruplex
      sequence were used as signal amplification elements. In the presence of Hg2+, the
      T-Hg2+-T mismatch resulted in disassembling the THMS and releasing the initiator
      probe. One of the hairpins was opened by the released initiator probe, which
      triggered a successive cross-opening of two hairpins based the strand
      displacement principle, resulting in the formation of long-chain DNA with
      multiple G-quadruplex. When thioflavin T (ThT), a fluorophore, was bound to the G
      quadruplex, an obvious fluorescence enhancement would occur. This sensing system
      enabled the highly sensitive and selective detection of aqueous Hg2+ with a limit
      of-detection of 10.2 pM.

PMID- 29225221
TI  - A New Kinetic, Automated Assay to Determine the Ferroxidase Activity of
      Ceruloplasmin.
AB  - A new kinetic and automated assay was developed to determine ceruloplasmin
      ferroxidase activity. Ferrous ions are turned into ferric ions via catalytic
      activity of the ferroxidase enzyme. Acetohydroxamic acid, a chromogen, forms a
      colored complex with ferric ions. This reaction was measured kinetically.
      Significant and strong correlations were obtained between the new acetohydroxamic
      method and the p-phenylenediamine oxidase (r = 0.988, p <0.001), o-dianisidine
      oxidase (r = 0.981, p <0.001), norfloxacine oxidase (r = 0.989, p <0.001) and
      nephelometric methods (r = 0.861, p <0.001). This reliable, applicable, user
      friendly, and low-priced method can be performed fully automatically or with
      manual spectrophotometry, and can be used to measure the ferroxidase activity of
      ceruloplasmin.

PMID- 29225222
TI  - Autofluorescent Hyperbranched Poly(amide amine) as Effective Fluorescent Probe
      for Label-free Detection of Copper(II) Ions.
AB  - A label-free fluorescent probe based on autofluorescent hyperbranched poly(amide
      amine) (HPAMAM) for copper ions was designed. HPAMAM is a cationic polymer
      containing many amino groups, which could bind Cu2+ ions to form cupric amine
      complexes, leading to a selective quenching of the fluorescence intensity of
      HPAMAM via inner filter effect. The fluorescence intensity of HPAMAM decreased
      with increasing concentration of Cu2+ ions and the linear response ranged from
      0.05 to 25 MUM (R2 = 0.995), with the corresponding detection limit (3sigma/k) of
      17.15 nM. The HPAMAM fluorescent probe provided a simple, rapid, selective and
      sensitive fluorometric method for detecting Cu2+ ions, which could be also
      applied for detection of Cu2+ ions in real water samples.

PMID- 29225223
TI  - pH-Independent Recognition of Polyhydroxy Compounds by Niobium(V) Porphyrin
      Complex with Unique Sugar Selectivity.
AB  - The niobium(V) complex with tetraphenylporphin having OH- as an auxilliay ligand
      exists as a dimeric complex, [Nb2(tpp)2O3] at a total concentration >10-4.5 mol
      dm-3, and reacts with an aliphatic or aromatic polyhydroxy compound to form a
      monomeric complex containing chelate rings by coordination of the deprotonated
      species, and to cause an appreciable UV-Vis spectral change. In contrast to
      phenylboronic acid (PBA), the reactivity of [Nb2(tpp)2O3] is independent of pH at
      least between 4 and 8. Aliphatic comounds are more reactive than aromatic
      compounds in dioxane-water, while the reactivity order is reversed in the two
      phase reaction. The sugar selectivity order of [Nb2(tpp)2O3] in dioxane-water
      (10:1) (sorbose > fructose >> mannose > arabinose, galactose > glucose) is
      appreciably different from that of PBA (fructose > sorbose >> arabinose >
      galactose > mannose > glucose). This may be related to the difference in size of
      the Lewis acidic center.

PMID- 29225224
TI  - Characterization of Melanin Radicals in Paraffin-embedded Malignant Melanoma and
      Nevus Pigmentosus Using X-band EPR and EPR Imaging.
AB  - Continuous wave electron paramagnetic resonance (CW EPR) and X-band (9 GHz) EPR
      imaging (EPRI) were used to nondestructively investigate the possible
      differentiation between malignant melanoma (MM) and nevus pigmentosus (NP)
      melanin radicals in paraffin-embedded specimens. The EPR spectra of both samples
      were analyzed using linewidth, spectral pattern, and X-band EPRI. The CW-EPR
      spectra of the MM showed an additional signal overlap. Eumelanin- and pheomelanin
      related radicals were observed in the MM specimens. The EPR results revealed that
      the peak-to-peak linewidths (DeltaHpp) of paraffin-embedded MM and NP samples
      were 0.65 +/- 0.01 and 0.69 +/- 0.01 mT, respectively. The g-value was 2.005 for
      both samples. Moreover, the two-dimensional (2D) EPRI of the MM showed different
      signal intensities at the different tumor stages, unlike the NP, which displayed
      fewer variations in signal intensity. Thus, the present results suggest that EPR
      and 2D EPRI can be useful for characterization of the two melanin radicals in the
      MM and for determination of their size and concentration.

PMID- 29225225
TI  - Internal Standard-Amplitude Modulated Multiplexed Flow Analysis.
AB  - A new concept of flow analysis, internal standard-amplitude modulated multiplexed
      flow analysis, is proposed. A proof of concept was verified by applying it to the
      determination of ferrous ion (Fe2+) by 1,10-phenanthroline (o-Phen)
      spectrophotometry. The flow rates of sample solutions containing Methylene Blue
      (MB) as an internal standard substance were sinusoidally varied at different
      frequencies. The solutions were merged with a color reagent (o-Phen) solution,
      while the total flow rate was held constant. Downstream, analytical signals were
      monitored at the maximum absorption wavelengths of Fe2+-o-Phen complex and of MB
      (510 and 644 nm, respectively). The signals were respectively analyzed by fast
      Fourier transform. The concentrations of the analytes in respective samples were
      simultaneously determined from the amplitudes of the corresponding wave
      components. The precision, linearity of the calibration curve, limit of detection
      and robustness against deliberate fluctuation in flow rate were greatly improved
      by introducing the internal standard method. Good recoveries of around 100% were
      obtained for Fe2+ spiked into real water samples.

PMID- 29225226
TI  - A Novel Biosensor Based on Terminal Protection and Fluorescent Copper
      Nanoparticles for Detecting Potassium Ion.
AB  - A novel biosensor for sensitively detecting potassium ion (K+) has been developed
      based on fluorescent copper nanoparticles (Cu NPs). In our design, we employ a
      label-free single-strand DNA (ssDNA) that contains two parts. One is 3'-terminus
      structure-switching aptamers (SSAs) that can fold into G-quadruplex after binding
      with its target K+. The other is 5'-terminus poly thymine (polyT) which works as
      a template to construct fluorescent Cu NPs. After incubating with K+, the part
      SSAs go through target-induced conformational changes. Benifiting from the
      exceptional digestion ability of exonuclease I (Exo I), the G-quadruplexes
      display effective resistance to nuclease digestion, so that 5'-terminus polyT
      remains and the in situ formation of Cu NPs provides a turn-on fluorescent signal
      that is used to evaluate the concentration of K+. The recovery of the
      fluorescence intensity is linearly correlated with the K+ concentration in the
      range of 0.05 to 1 mM with a detection limit of 0.05 mM. Compared with some
      methods, this assay is cost-effective and facile with high specificity.
      Meanwhile, this excellent strategy shows a great potentiality in other sensing
      approaches that can study the interaction between similar SSAs and different
      specific targets.

PMID- 29225227
TI  - Selective Detection of Carcinogenic Aromatic Diamines in Aqueous Solutions Using
      4-(N-Chloroformylmethyl-N-methylamino)-7-nitro-2,1,3-benzoxadiazole (NBD-COCl) by
      HPLC.
AB  - Reaction conditions for the selective derivatization of three types of aromatic
      diamines without clean-up in an aqueous solution using 4-(N-chloroformylmethyl-N
      methylamino)-7-nitro-2,1,3-benzoxadiazole (NBD-COCl) have been developed for
      simple, fast, and selective analysis by HPLC. The aromatic amines were
      derivatized to give di-NBD-CO-aromatic amines at 35 degrees C for 5 min in a
      buffer solution at pH 5 containing a low acetonitrile concentration (0 - 400
      ng/mL, n = 5, r >0.998). The retention times of these di-NBD-CO-aromatic amines
      were <5 min. Sample solutions containing aromatic amines, phenols, and an
      aliphatic amine were also prepared. Under the optimized reaction conditions
      (i.e., low acetonitrile content and acidic conditions), no derivatization of the
      phenols and the aliphatic amine was observed. These were related to the
      differences in the pKa values of the target substances, the organic solvent
      concentration, and the reaction solution pH. For the model system, a sulfuric
      acid-impregnated filter was spiked with the aromatic amines, phenols, and
      aliphatic amine prior to extraction, derivatization, and measurement by HPLC.
      Only aromatic amines were detected quantitatively, with no other compounds being
      observed.

PMID- 29225228
TI  - Zinc Ion-immobilized Magnetic Microspheres for Enrichment and Identification of
      Multi-phosphorylated Peptides by Mass Spectrometry.
AB  - The selective isolation of phosphorylated peptides and subsequent analysis using
      mass spectrometry is important for understanding how protein kinase and
      phosphatase signals can precisely modulate the on/off states of signal
      transduction pathways. However, the isolation and detection of multi
      phosphorylated peptides is still limited due to their distinct affinity to
      various materials and their poor ionization efficiency. Here, we report a highly
      efficient and selective enrichment of phosphorylated peptides using binuclear
      Zn2+-dipicolylamine complex-coated magnetic microspheres (ZnMMs). ZnMMs can
      utilize the rapid and selective isolation/enrichment of phosphorylated peptides
      and the subsequent mass spectrometric analysis, given the intrinsic magnetic
      property of magnetic microspheres and the highly selective binding ability of the
      binuclear Zn2+-dipicolylamine complex to phosphate groups. alpha-Casein and beta
      casein were chosen for a proof-of-concept demonstration. We contemplated that
      phosphopeptides were selectively isolated and enriched from both the tryptic
      digests of casein proteins and mixed samples with a high degree of sensitivity by
      facilitating ZnMMs. Especially, ZnMMs showed high efficiency with multi
      phosphopeptides, which are in general difficult to be examined by mass analysis
      on account of their poor ionization efficiency. For the model protein alpha, beta
      casein mixture of the tryptic digest, 17 phosphopeptides were identified with
      ZnMMs and 82% of the enriched phosphopeptides were multi-phosphorylated peptides,
      indicating that ZnMMs have excellent enrichment efficiency and strong affinity
      towards multi-phosphorylated peptides.

PMID- 29225229
TI  - NHS-based Tandem Mass Tagging of Proteins at the Level of Whole Cells: A Critical
      Evaluation in Comparison to Conventional TMT-Labeling Approaches for Quantitative
      Proteome Analysis.
AB  - Tandem mass tags (TMT) are usually introduced at the levels of isolated proteins
      or peptides. Here, for the first time, we report the labeling of whole cells and
      a critical evaluation of its performance in comparison to conventional labeling
      approaches. The obtained results indicated that TMT protein labeling using intact
      cells is generally possible, if it is coupled to a subsequent enrichment using
      anti-TMT antibody. The quantitative results were similar to those obtained after
      labeling of isolated proteins and both were found to be slightly complementary to
      peptide labeling. Furthermore, when using NHS-based TMT, no specificity towards
      cell surface proteins was observed in the case of cell labeling. In summary, the
      conducted study revealed first evidence for the general possibility of TMT cell
      labeling and highlighted limitations of NHS-based labeling reagents. Future
      studies should therefore focus on the synthesis and investigation of membrane
      impermeable TMTs to increase specificity towards cell surface proteins.

PMID- 29225230
TI  - In situ Measurement of the pH-dependent Transmission Infrared Spectra of Aqueous
      Lactic Acid Solutions.
AB  - The transmission infrared absorption spectra of an aqueous lactic acid solution
      was measured over a pH range of 2.66 - 1.59 using a cell with an optical path
      length of 12 MUm. Absorption peaks were then identified by density functional
      theory (DFT) calculations. The observed pH-dependent changes in the absorbance
      spectra were consistent with the properties of the assigned functional groups. We
      therefore believe that the present method can be applied to the contactless and
      non-invasive quantitative evaluation of pH values in aqueous systems, such as
      bioprocesses and bioimaging.

PMID- 29225231
TI  - Kinetic Determination of Lanthanum(III) by the Catalytic Effect on the Oxidation
      of Fluorescent Safranine Dyes with Potassium Bromate.
AB  - Two simple and sensitive kinetic-fluorometric methods have been developed for the
      determination of lanthanum(III): fluorescence quenching generated by the
      oxidation of safranine T or phenosafranine with potassium bromate in an acetate
      buffer solution. The rate of the oxidation reaction is significantly accelerated
      after adding lanthanum(III). A good linearity between the relative fluorescence
      intensity and lanthanum(III) is observed in the range of both 0.04 - 2.0 and 4.0 
      16 MUg/mL. The detection limits have been 3.6 * 10-3 and 0.334 MUg/mL
      respectively. The accuracy and reliability of the methods are further validated
      by recovery studies via a standard-addition method, with percentage recoveries
      ranging from 98 to 102%. Comparing the results of two measured reaction systems,
      we find that the safranine T reaction system provides high sensitivity and a
      wider linear range. In consequence, we have chosen the safranine T system to
      detect sample water, and explored the reaction mechanism.

PMID- 29225232
TI  - Effect of Ultraviolet Irradiation on Proton Transfer Facilitated by 5,10,15,20
      Tetraphenyl-21H,23H-porphine and Its Metal Complexes at a Water/1,2
      Dichloroethane Interface.
AB  - We examined photochemical effects by ultraviolet irradiation on facilitated
      proton transfer at a water/1,2-dichloroethane (W/DCE) interface by ion-transfer
      voltammetry using a Xe flash lamp. 5,10,15,20-Tetraphenyl-21H,23H-porphine
      (H2TPP) or its metal complex, such as cobalt (Co(II)TPP), zinc (Zn(II)TPP), and
      nickel (Ni(II)TPP) complexes, was added into the DCE phase as an ionophore for
      the facilitated proton transfer. After we irradiated the W/DCE interface through
      the W phase, the voltammetric waves for proton transfer facilitated by H2TPP and
      Co(II)TPP were remarkably enhanced and shifted to the lower potential region,
      compared to those before irradiation. We confirmed from the pH and argentometric
      titrations that such enhancements and shifts of the waves were caused by hydrogen
      chloride (HCl) produced by photodecomposition of DCE. On the other hand, the
      waves for proton transfer facilitated by Zn(II)TPP and Ni(II)TPP were very small
      from the beginning, and showed neither enhancement nor any shift upon
      irradiation.

PMID- 29225233
TI  - Copper Nanoparticles for Ascorbic Acid Sensing in Water on Carbon Screen-printed
      Electrodes.
AB  - A carbon screen-printed electrode was modified with copper nanoparticles from
      their dispersion obtained via pulsed laser ablation of a copper target in
      ethanol. The modified electrode exhibited activity in ascorbic acid
      electrochemical oxidation, giving an anodic current peak on voltammograms. Linear
      sweep and cyclic voltammetry have shown a linear dependence of the signal (both
      peak height and peak area) on the ascorbic acid concentration. The linear range
      from 1 to 250 MUM of ascorbic acid was studied, and the detection limit was
      experimentally found to be 0.5 MUM. The amperometric response to the addition of
      ascorbic acid portions into the solution was recorded. For the case of the
      simultaneous presence of ascorbic acid and glucose, two separate signal were
      obtained. Thus, the modified electrodes are characterized by the following
      advantages: disposable use; small amount of the samples required for the
      analysis; lower price (cheap copper is used); simple and easy modification
      procedure; good metrological characteristics; selectivity.

PMID- 29225234
TI  - A Planar Bilayer Lipid Membrane Sensor Using a Miniaturized Auto-patch System.
AB  - A bilayer lipid membrane sensor was constructed with a miniaturized auto-patch
      system. The performance of the patch system was optimized to obtain an
      analytically relevant signal. A biosensor based on an anti-BSA-antibody as a
      receptor and gramicidin as a signal transduction element was demonstrated. The
      sensor for BSA exhibited a detection limit of pg/mL level for BSA.

PMID- 29225235
TI  - Solid Phase Extraction of Trace Al(III), Fe(II), Co(II), Cu(II), Cd(II) and
      Pb(II) Ions in Beverages on Functionalized Polymer Microspheres Prior to Flame
      Atomic Absorption Spectrometric Determinations.
AB  - In this study, poly(glycidyl methacrylate-methyl methacrylate-divinylbenzene) was
      synthesized in the form of microspheres, and then functionalized by 2
      aminobenzothiazole ligand. The sorption properties of these functionalized
      microspheres were investigated for separation, preconcentration and determination
      of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions using flame atomic
      absorption spectrometry. The optimum pH values for quantitative sorption were 2 -
      4, 5 - 8, 6 - 8, 4 - 6, 2 - 6 and 2 - 3 for Al(III), Fe(II), Co(II), Cu(II),
      Cd(II) and Pb(II), respectively, and also the highest sorption capacity of the
      functionalized microspheres was found to be for Cu(II) with the value of 1.87
      mmol g-1. The detection limits (3sigma; N = 6) obtained for the studied metals in
      the optimal conditions were observed in the range of 0.26 - 2.20 MUg L-1. The
      proposed method was successfully applied to different beverage samples for the
      determination of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions, with
      the relative standard deviation of <3.7%.

PMID- 29225236
TI  - Microfluidic Platform for Analyzing the Thermotaxis of C. elegans in a Linear
      Temperature Gradient.
AB  - Caenorhabditis elegans (C. elegans), which shares a considerable amount of
      characteristics with human genes is one of the important model organisms for the
      study of behavioral responses. Thermotaxis is a representative behavior response
      of C. elegans; C. elegans stores the cultivation temperature in thermosensory
      neurons and moves to the cultivation temperature region in a temperature
      variation. In this study, we developed a microfluidic system for effective
      thermotaxis analysis of C. elegans. The microfluidic channel was fabricated using
      polydimethylsiloxane (PDMS) by soft lithography process. The temperature gradient
      (15 - 20 degrees C) was generated in the microchannel and controlled by Peltier
      modules attached to the bottom of the channel. The thermotaxis of wild type (N2),
      tax-4(p678) and ttx-7(nj50) mutants were effectively analyzed using this
      microfluidic system. We believe that this system can be employed as a basic
      platform for studying the neural circuit of C. elegans responding to external
      stimuli.

PMID- 29225237
TI  - A Biotin-streptavidin-enhanced Carbon Nanotube Amplification Strategy for an
      Ultrasensitive Immunodetection of Polybrominated Diphenyl Ethers.
AB  - The extensive use of polybrominated diphenyl ethers (PBDEs) has resulted in its
      increasingly widespread presence. Especially the lower halogenated PBDEs
      accumulate to a greater degree than the higher halogenated PBDEs in house dust,
      sewage sludge, pets, or even humans. In the present work, we developed an
      ultrasensitive biotin-streptavidin-enhanced carbon nanotube amplification
      strategy for the immunodetection of PBDEs, in which single-walled carbon
      nanotubes were used to immobilize numerous streptavidin. Meanwhile, we used
      biotin conjugated horseradish peroxidase (B-HRP) and biotin conjugated Goat anti
      rabbit (B-IgG) to link the HRP and IgG to CNTs by using a biotin-streptavidin
      system. The sensitivity of the streptavidin-biotin-IgG-CNTs-HRP bioconjugate was
      compared with a commercial HRP-labelled IgG by using indirect competitive ELISA.
      The limit of this proposed ELISA detection (IC10) was 0.0059 ng/mL, showing a 20
      time lower detection limit over the commercial one (IC10 = 0.1193 ng/mL).
      Finally, we applied the assay to the detection of PBDEs in dust samples. The
      results were consistent with those using GC-ECD, which confirmed that the
      proposed amplification strategy was accurate and receptive. This proposed biotin
      streptavidin-enhanced carbon nanotube amplification strategy would be useful for
      ultrasensitive immunodetection in environmental studies.

PMID- 29225238
TI  - Distribution Equilibria of Amphoteric 8-Quinolinol between 1-Alkyl-3
      methylimidazolium Bis(trifluoromethanesulfonyl)imide and Aqueous Phases and Their
      Effect on Ionic Liquid Chelate Extraction Behavior of Iron(III).
AB  - The distribution behavior of amphoteric 8-quinolinol (HQ) between ionic liquid
      (IL) phase and aqueous phase and ionic liquid chelate extraction behavior of
      iron(III) with HQ were investigated using four 1-alkyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide (CnmimTf2N, n = 2, 4, 6 and 8) ILs. Not only
      neutral HQ but also cationic H2Q+ were distributed into the IL phase, and the
      latter distribution based on cation-exchange with Cnmim+ was pronounced in the
      use of IL having a less-hydrophobic cation, such as C2mim+. In the IL chelate
      extraction of iron(III), the extractability increased with the increase in the
      hydrophobicity of IL as the extraction phase. Nevertheless, the determined
      equilibrium constants for the extraction as the neutral complex FeQ3 were similar
      to one another. The difference in the extractability among the ILs was due to the
      difference in the distribution of H2Q+ into the extraction phase. In addition,
      the cationic coordinatively-unsaturated complex FeQ2+ was also extracted in use
      of less-hydrophobic C2mimTf2N.

PMID- 29225239
TI  - Rapid Plasma Etching for Fabricating Fused Silica Microchannels.
AB  - In order to advance the performances of micro chemical and biochemical systems on
      a chip, the fabrication of microstructures such as channels and pillars is an
      essential basic technology. However, conventional fabrication methods based on
      wet etching have limitations in their applications for device engineering. In
      this study, we report on a new microchannel fabrication process on a fused silica
      substrate using photoresist and plasma etching based on C3F8, CHF3, and Ar gases.
      Deep, rectangular microchannels, having vertical angles close to 90 degrees , 10
      MUm-scale deep and low surface roughness of less than 1 nm, could be fabricated
      on a fused silica substrate at high etching rates on the order of 5 - 7 nm s-1.
      This metal-free fabrication methodology is expected to be a low-cost, easy, and
      simple technique for a fused silica microstructure applications.

PMID- 29225240
TI  - A Fluorescence Quenching Assay Based on Molecular Beacon Formation through a
      Ligase Detection Reaction for Facile and Rapid Detection of Point Mutations.
AB  - A fluorescence quenching assay based on a ligase detection reaction was developed
      for facile and rapid detection of point mutations present in a mixed population
      of non-variant DNA. If the test DNA carried a targeted mutation, then the two
      allele-specific primers were ligated to form a molecular beacon resulting in the
      expected fluorescence quenching signatures. Using this method, we successfully
      detected as low as 5% mutant DNA in a mixture of wild-type DNA (t test at 99%
      confidence level).

PMID- 29225241
TI  - Effect of the Elemental Composition of Precursors from Amino Acids and Their
      Binary Mixtures on the Photoluminescent Intensity of Carbon Nanodots.
AB  - We report on the photoluminescent (PL) properties of carbon nanodots (CNDs) doped
      with nitrogen and sulfur obtained by the pyrolytic carbonization of amino acids
      as precursors. Prepared CNDs exhibit stable PL emission under a wide variety of
      aqueous conditions. The results also provided the way to tune a PL intensity of
      CNDs by varying the amount of heteroatoms in precursors with a binary mixture of
      amino acids. The PL quantum yields of the obtained CNDs were determined to be
      from 0.079 to 0.571.

PMID- 29225242
TI  - Newly Developed Friction Tester for in situ Soft X-Ray Absorption Measurements of
      Frictional Engine-Oil/Metals Interfaces.
AB  - A novel friction tester has been developed to clarify the friction mechanism
      between engine oil and metals by in situ/operando measurements of the X-ray
      absorption near edge structure (XANES) using the total electron yield (TEY)
      method. The tester can perform frictional motion with engine oil and metals in a
      vacuum chamber under a vacuum of 10-7 Torr during TEY-XANES measurements in BL
      6.3.2 at the Advanced Light Source (ALS). From in situ XANES measurements in the
      C K and Fe L regions, the organic molecule layers at the oil/metals interfaces
      have been successfully observed.

PMID- 29225244
TI  - Trousseau's Syndrome Causing Refractory Deep Venous Thrombosis.
AB  - A 66-year-old man, who had been diagnosed with deep venous thrombosis (DVT), and
      who was treated with a vitamin K antagonist (VKA) and who had undergone the
      implantation of an inferior vena cava filter, was admitted due to an exacerbation
      of DVT. VKA was administered again; however, the patient's DVT worsened. Further
      examinations revealed colon cancer, which led to a diagnosis of Trousseau's
      syndrome. The regression of the thrombi was confirmed after the administration of
      heparin and the resection of the tumors. Trousseau's syndrome should always be
      kept in mind when patients present with refractory venous thrombosis. The
      administration of heparin, and cancer control are necessary for the effective
      treatment of thrombosis in such cases.

PMID- 29225245
TI  - Oral Methotrexate-related Lymphoproliferative Disease Presenting with Severe
      Osteonecrosis of the Jaw: A Case Report and Literature Review.
AB  - Long-term methotrexate (MTX) treatment can cause MTX-related lymphoproliferative
      disorder (MTX-LPD). We experienced a case of MTX-LPD that was associated with
      severe osteonecrosis of the jaw mimicking medication-related osteonecrosis of the
      jaw. The patient was an 81-year-old woman with rheumatoid arthritis (RA) who was
      treated with MTX and bisphosphonate. After 7 years, she was referred to our
      department for the assessment of giant ulcer and exposure of the alveolar bone of
      the left maxilla. Histopathological and immunological analyses confirmed a
      diagnosis of MTX-LPD. At seven months after the cessation of MTX treatment, the
      ulcerative and necrotic lesions had markedly decreased in size. A 1-year follow
      up examination showed no evidence of recurrence and good RA control.

PMID- 29225246
TI  - Acute Arterial Thrombosis during Postoperative Adjuvant Cisplatin-based
      Chemotherapy for Completely Resected Lung Adenocarcinoma.
AB  - A malignant tumor can cause hypercoagulation and it also often coexists with
      thrombosis. Cisplatin-based chemotherapy can also induce adverse vascular
      effects, including arterial thrombosis. We herein report a case of acute arterial
      thrombosis in a patient undergoing postoperative adjuvant cisplatin-based
      chemotherapy for completely resected lung cancer. The patient complained of acute
      leg pain after chemotherapy, and computed tomography revealed multiple thrombi
      from the thoracic to popliteal arteries. Arterial thrombosis during adjuvant
      chemotherapy is extremely rare; however, careful clinical observation of patients
      receiving cisplatin-based chemotherapy is important, because arterial thrombosis,
      even in the absence of the primary malignant tumor, is possible.

PMID- 29225247
TI  - Hypercalcemia after the Discontinuation of Medroxyprogesterone Acetate.
AB  - A 39-year-old woman was admitted to our hospital with symptoms of general
      fatigue, nausea, and vomiting that appeared three months after she stopped seven
      years of medroxyprogesterone acetate (MPA) medication for endometrial stromal
      sarcoma. Laboratory tests demonstrated moderate hypercalcemia. Several tests
      demonstrated that she was suffering from adrenal insufficiency. Glucocorticoid
      supplementation decreased her calcium level to a normal range, indicating that
      hypercalcemia was induced by adrenal insufficiency. It was suggested that she was
      suffering from MPA-induced adrenal insufficiency, but hypocortisolemia was being
      compensated by a high dose of MPA; hypocortisolemia and hypercalcemia then became
      evident after MPA treatment was discontinued.

PMID- 29225248
TI  - Reversible Left Ventricular Wall Thickening with Takotsubo Syndrome Sequentially
      Detected by Cardiac Magnetic Resonance Imaging.
AB  - Recently, it has been reported that spontaneous left ventricular wall thickening
      occurs among patients with takotsubo syndrome, which affects the long-term
      prognosis of such patients due to cerebral and cardiac complications. We herein
      report two cases of transient left ventricular wall thickening with takotsubo
      syndrome in which sequential cardiac magnetic resonance imaging revealed the
      existence of edematous changes in the thickened wall. Notably, a left ventricular
      aneurysm was detected during the course of ventricular wall thickening and may
      have played a role in the development of serious complications accompanied by
      takotsubo syndrome. This is the first case report of left ventricular aneurysm
      occurring with ventricular wall thickening due to takotsubo syndrome.

PMID- 29225249
TI  - Acute Tetraparesis with Respiratory Failure after Steroid Administration in a
      Patient with a Dural Arteriovenous Fistula at the Craniocervical Junction.
AB  - A 63-year-old man developed vomiting, paraparesis, dysuria, bulbar palsy, and
      orthostatic hypotension over a period of 5 months. Neuroradiological examinations
      showed a swollen lower brainstem with a dural arteriovenous fistula at the
      craniocervical junction (DAVF-CCJ). A steroid was administered intravenously in
      the hospital to relieve brainstem edema. A few hours later, however, the patient
      developed acute tetraparesis with respiratory failure. Recently, there have been
      several reports describing the acute worsening of paraparesis in patients with a
      spinal dural arteriovenous fistula after steroid treatment. In addition to these
      reports, the present case suggests the risk of administering steroids to patients
      with DAVF-CCJ, especially those with brainstem dysfunction.

PMID- 29225250
TI  - Importance of the Average Glucose Level and Estimated Glycated Hemoglobin in a
      Diabetic Patient with Hereditary Hemolytic Anemia and Liver Cirrhosis.
AB  - Glycated hemoglobin (HbA1c) is a widely used marker of glycemic control but can
      be affected by hemolytic anemia. Glycated albumin (GA) is also affected in
      patients with liver cirrhosis. We herein report the assessment of glycemic
      control in a 41-year-old man with dehydrated hereditary stomatocytosis and a
      PIEZO1 gene mutation complicated by diabetes mellitus and liver cirrhosis due to
      hemochromatosis. The estimated HbA1c calculated from the average glucose level
      obtained by continuous glucose monitoring or by self-monitoring of blood glucose
      was useful for evaluating the glycemic control in this patient, as HbA1c and GA
      were unreliable due to the coexisting conditions.

PMID- 29225251
TI  - Successful Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion
      Associated with Neuro-Sweet Disease in Myelodysplastic Syndrome.
AB  - Sweet disease may occur in several organs, and central nervous system
      involvement, known as Neuro-Sweet disease (NSD), is rare. The clinical features
      of NSD include recurrent encephalomeningitis accompanied by fever and
      erythematous plaques; systemic corticosteroid therapy is highly effective.
      Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an important
      electrolyte abnormality because it can be life-threatening. We describe the first
      case of SIADH and NSD associated with low-risk myelodysplastic syndrome that was
      successfully treated with corticosteroids and cyclosporine. The patient has
      remained stable for 1 year without any recurrence.

PMID- 29225252
TI  - Reactivation of Hemophagocytic Lymphohistiocytosis Triggered by Antithymocyte
      Globulin.
AB  - A 16-year-old boy with Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis (HLH) underwent allogeneic hematopoietic stem cell
      transplantation after conditioning with fludarabine, melphalan, total body
      irradiation, and rabbit antithymocyte globulin (ATG). A severe, persistent
      infusion reaction occurred after the initial administration of ATG.
      Investigations showed a rapid increase in the levels of liver enzymes and
      ferritin, and the reactivation of HLH was confirmed by marked hemophagocytosis in
      the bone marrow. Treatment with pulse glucocorticoid therapy resulted in the
      improvement of HLH. This is the first case of HLH reactivation triggered by ATG.
      Physicians should therefore be cautious of HLH reactivation, especially when a
      severe and prolonged infusion reaction occurs.

PMID- 29225253
TI  - An Analysis of the Neuropathic Pain Components in Rheumatoid Arthritis Patients.
AB  - Objective To analyze the neuropathic pain (NeP) components in patients with
      rheumatoid arthritis (RA). Methods The painDETECT questionnaire (PD-Q) was
      completed by 300 RA patients (79 men, 221 women). Results Nine patients (3.0%)
      were categorized as likely NeP, 33 (11.0%) were categorized as possible NeP, and
      258 (86.0%) were categorized as unlikely NeP. When we excluded patients with
      diabetes mellitus, spinal diseases, neurological diseases, and herpes zoster
      infection (conditions associated with NeP), 5 of the patients (1.7%) had likely
      NeP, and 23 (7.7%) had possible NeP without any underlying conditions.
      Furthermore, there were no marked differences in the percentages of these
      underlying conditions among the patients with likely, possible, and unlikely NeP.
      When we compared patients with likely and possible NeP (n=42) and unlikely NeP
      (n=258), the body mass index (BMI), disease activity score-28 based on the
      erythrocyte sedimentation rate, C-reactive protein level, pain visual analogue
      scale (VAS), and PD-Q score were significantly higher in the patients with likely
      and possible NeP than in those with unlikely NeP. A multivariate analysis showed
      that BMI >=22 and not being in clinical remission were associated with NeP.
      Conclusion Although RA pain has usually been classified as nociceptive pain, the
      present study clarified that a significant number of patients might have NeP. The
      present findings suggest that high disease activity and being overweight are
      related to NeP in RA patients.

PMID- 29225254
TI  - Observational Study of Infective Endocarditis at a Community-based Hospital:
      Dominance of Elderly Patients with Comorbidity.
AB  - Objective The purpose of this study was to present the recent clinical profiles
      and the real-world management of infective endocarditis (IE). Methods All medical
      records of patients with IE were reviewed retrospectively for their clinical
      data, including clinical presentation, laboratory results, blood cultures,
      echocardiographic findings, treatments and complications. Using the clinical data
      collected, we calculated the EuroSCORE II, the European risk score for adult
      cardiac surgery, the Charlson Comorbidity Index as a surrogate of comordibity,
      and the Katz Index as a surrogate of frailty. Results Thirty-eight patients were
      identified as having IE (24 men, age: 71.8+/-13.1 years). Congestive heart
      failure occurred in 16 patients (42%), stroke in 14 (50%), and systemic embolism
      in 5 (13%). The EuroSCORE II and Charlson Comorbidity Index were high (7.7+/-5.8%
      and 5.5+/-2.8%, respectively). The Katz Index was fair (5.5+/-1.4) before the
      onset but deteriorated to 2.8+/-2.7 at the time of establishing the diagnosis of
      IE (p<0.001). Early surgery was performed in 22 cases (61%). In-hospital death
      occurred in 10 cases (26%). A EuroSCORE II >=9%, Staphylococcus aureus etiology,
      and a Charlson Comorbidity Index were suggested as determinants of in-hospital
      death (hazard ratios: 173.60, 9.31, 1.57, respectively). In contrast, early
      surgery was suggested as a determinant of the survival (hazard ratio: 0.04). The
      Charlson Comorbidity Index was also suggested as a determinant for selecting
      conservative management (odds ratio: 1.40). Conclusion Comorbidity may influence
      the treatment selection and outcome of elderly patients with IE.

PMID- 29225255
TI  - Edwardsiella tarda Bacteremia with Psoas and Epidural Abscess as a Food-borne
      Infection: A Case Report and Literature Review.
AB  - Edwardsiella tarda is commonly isolated from aquatic environments and a variety
      of animals. We present the first case of E. tarda bacteremia with psoas and
      epidural abscess. The patient was a 65-year-old woman with recurrent gastric
      cancer who had frequently consumed raw fish and grilled eel. She was successfully
      treated with antimicrobials and surgery. We also review reports published in
      English regarding E. tarda bacteremia in Japan and the experience at our
      hospital. On the basis of this review, we conclude that the major underlying
      disease leading to E. tarda bacteremia is malignancy and that the
      gastrointestinal tract is the most commonly affected organ. The overall mortality
      rate due to E. tarda bacteremia in our review was 38.1% (8/21). Although E. tarda
      bacteremia is rare, clinicians should be aware of this fatal food-borne
      infection.

PMID- 29225257
TI  - Isolated Dissection of the Superior Mesenteric Artery.

PMID- 29225256
TI  - Gastric Adenocarcinoma of the Fundic Gland Type after Endoscopic Therapy for
      Metachronous Gastric Cancer.
AB  - A 78-year-old man underwent endoscopic submucosal dissection (ESD) for early
      gastric adenocarcinoma twice in 2009 and 2014. Between the procedures, he
      successfully completed Helicobacter pylori eradication therapy. In May 2015,
      upper endoscopy screening showed two elevated lesions on the gastric fundus, and
      en bloc resection by ESD was performed. We histopathologically diagnosed the
      patient to have gastric adenocarcinoma of the fundic gland type. In this case,
      the two lesions of gastric adenocarcinoma of the fundic gland type multifocally
      developed after ESD for metachronous gastric tubular adenocarcinoma. Furthermore,
      they appeared in the gastric fundus, where atrophy had been improved due to
      eradication therapy.

PMID- 29225258
TI  - Isolated Cardiac Sarcoidosis Mimicking Arrhythmogenic Right Ventricular
      Cardiomyopathy.
AB  - The diagnosis of cardiac sarcoidosis (CS) has become easier due to advances in
      imaging modalities, but we sometimes encounter difficult-to-diagnose patients. We
      herein report the case of a 60-year-old Japanese woman who was diagnosed with
      isolated CS, although she also met the diagnostic criteria of arrhythmogenic
      right ventricular cardiomyopathy (ARVC). A histological examination by an
      endomyocardial biopsy of the right ventricle revealed the typical findings of
      granulomatous change for CS. Although she did not show any characteristics of
      systemic sarcoidosis, oral prednisolone treatment was introduced, and she
      achieved a good response. This case shows that the characteristics of CS can
      overlap with the diagnostic criteria of ARVC, and that a histological examination
      is essential for the correct diagnosis of CS.

PMID- 29225259
TI  - The Diagnostic Yield of Urine Cultures with Liquid Media in Cases of Miliary
      Tuberculosis.

PMID- 29225260
TI  - Hyperparathyroidism-jaw Tumor Syndrome Confirmed by Preoperative Genetic Testing.
AB  - We herein report the case of a young woman who was diagnosed with primary
      hyperparathyroidism and in whom genetic testing confirmed a diagnosis of
      hyperparathyroidism-jaw tumor syndrome. Familial hyperparathyroidism was
      suspected based on the patient's young age at the onset of the disease. Thus,
      genetic testing was performed. It showed a germline mutation in the HRPT2/CDC73
      gene and confirmed the diagnosis of hyperparathyroidism-jaw tumor syndrome. Total
      parathyroidectomy was performed to prevent recurrence. In patients with early
      onset hyperparathyroidism, genetic testing should be considered to facilitate the
      selection of a proper surgical procedure based on the consideration of future
      life expectancy.

PMID- 29225261
TI  - Isolated Left Atrial Infective Mural Endocarditis.
AB  - A 52-year-old man presented with a fever and malaise. Transthoracic
      echocardiogram was performed because of a holosystolic murmur, which showed
      mitral valve prolapse and a regurgitation jet toward the posterior wall of the
      left atrium. There was no apparent vegetation at any valves. Blood cultures were
      positive for Streptococcus mitis/oralis. Transesophageal echocardiogram revealed
      vegetation only at the posterior wall of the left atrium exposed to the mitral
      regurgitant jet. We diagnosed this condition as infective mural endocarditis.
      This case highlighted the need for a detailed observation of the valves and the
      atrial wall when infective endocarditis is suspected.

PMID- 29225262
TI  - The Effectiveness of Afatinib in a Patient with Advanced Lung Adenocarcinoma
      Harboring Rare G719X and S768I Mutations.
AB  - The uncommon mutations in the EGFR (the epithelial growth factor receptor) gene
      include a heterogeneous group of genomic alterations within exons 18-21. The
      clinical response of patients with such mutations to EGFR tyrosine kinase
      inhibitor (EGFR-TKI) treatment, however, remains unclear. We herein report a case
      of advanced lung adenocarcinoma harboring complex exon 18 G719X (Gly719Xaa) and
      exon 20 S768I (Ser768Ile) mutations. The patient started to receive afatinib and
      has exhibited good response without progression for 12 months. Second-generation
      EGFR-TKIs might be an optimal treatment option for non-small cell lung cancers
      harboring these types of rare EGFR mutation.

PMID- 29225263
TI  - A Phase I/II Study for Dose-finding, and to Investigate the Safety,
      Pharmacokinetics and Preliminary Efficacy of NK012, an SN-38-Incorporating
      Macromolecular Polymeric Micelle, in Patients with Multiple Myeloma.
AB  - Objective Multiple myeloma (MM) is the second most common hematological cancer.
      An attempt to treat MM using a topoisomerase I inhibitor was made based on our
      previous non-clinical studies suggesting the usefulness of an SN-38 derivative.
      Our aim was to conduct a phase I/II study of NK012, a micelle-forming SN-38
      conjugate, in patients with relapsed/refractory multiple myeloma (RRMM). Methods
      NK012 was administered at doses of 12-24 mg/m2 and the safety, pharmacokinetics
      and preliminary efficacy were evaluated. Results Neutropenia was the most common
      grade 3 or 4 adverse drug reaction. Grade 4 neutropenia accounted for the
      majority of dose-limiting toxicities and only appeared at a dose of 24 mg/m2. The
      maximum concentrations and the area under the concentration-time curves from time
      zero to infinity for both NK012 and its active metabolite SN-38 increased in a
      dose-dependent manner. The best overall response was stable disease, which was
      achieved in 12 out of 16 patients. Conclusion The recommended dose of NK012
      monotherapy for RRMM patients was concluded to be 20 mg/m2. However, this phase
      I/II study was terminated at the end of the phase I stage because no patients
      showed an objective response. Additional clinical studies of combination therapy
      with NK012 and other agents are warranted.

PMID- 29225264
TI  - A Homozygous LAMA2 Mutation of c.818G>A Caused Partial Merosin Deficiency in a
      Japanese Patient.
AB  - A complete loss of merosin, which is encoded by LAMA2, causes congenital muscular
      dystrophy with leukoencephalopathy. Partial merosin deficiency can be caused not
      only by primarily LAMA2 mutations, but also secondarily by dystroglycanopathy.
      Although it can be molecularly diagnosed based on a genetic analysis, this method
      is labor-intensive because of its huge genome size. A 26-year-old male patient
      presented with mild muscular weakness, joint contractures, and epilepsy. Double
      immunofluorescence staining of a muscle biopsy specimen showed mislocalization of
      merosin, and a genetic analysis revealed a homozygous c.818G>A (p.Arg273Lys)
      mutation in LAMA2. Double immunofluorescence staining and whole exome sequencing
      were useful for the diagnosis of partial merosin deficiency.

PMID- 29225265
TI  - Posterior Reversible Encephalopathy Syndrome after Lenvatinib Therapy in a
      Patient with Anaplastic Thyroid Carcinoma.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a rare reversible
      neurological syndrome that causes subcortical vasogenic brain edema and which is
      associated with the use of target-specific agents. Lenvatinib is a target
      specific agent that was recently approved for inoperable thyroid cancer. We
      herein describe the case of a 66-year-old woman with anaplastic thyroid cancer
      (ATC) who was treated with lenvatinib and who subsequently developed PRES. The
      clinical and radiological findings improved after suspending therapy for 1 week,
      and there was no recurrence with intermittent lower-dose lenvatinib treatment.
      Lenvatinib may prolong survival in patients with ATC and can be administered
      intermittently, even after PRES onset.

PMID- 29225266
TI  - Aortic Regurgitation Presenting with Recurrent Detachment of a Prosthetic Valve,
      as the First Presenting Symptom of Cardiovascular Behcet's Disease.
AB  - A 33-year-old man with severe aortic regurgitation underwent initial aortic valve
      replacement (AVR). During the 2 years after AVR, 3 reoperations for prosthetic
      valve detachment were required. During hospitalization, he had no typical
      clinical findings, with the exception of a persistent inflammatory reaction; a
      pseudo-aneurysm around the Bentall graft developed 27 days after the 4th
      operation. This unique clinical course suggested the possibility of Behcet's
      disease. In the 8 years of follow-up after the administration of prednisolone,
      the pseudo-aneurysm did not become enlarged and the detachment of the prosthetic
      valve was not observed. We herein present a case of cardiovascular Behcet's
      disease, with a review of the literature.

PMID- 29225267
TI  - A Rare Combination of Dermatomyositis, Interstitial Pneumonia, and Lung Cancer in
      a Patient Treated with Immunosuppressive Therapy and Chemotherapy.
AB  - We herein report the rare case of co-occurring dermatomyositis (DM), interstitial
      pneumonia (IP), and lung cancer in a 59-year-old man. Computed tomography (CT)
      and positron emission tomography-CT showed the presence of a left lung tumor with
      IP, which was diagnosed as lung adenocarcinoma by a CT-guided tumor biopsy. We
      diagnosed DM based on the presence of myalgia, Gottron's papules, and anti
      aminoacyl-tRNA synthetase antibody positivity in the patient. Co-occurrence of
      the above-mentioned three diseases is rare, and acute exacerbation of IP is a
      major cause of death in such cases. These patients can be treated with
      immunosuppressive therapy followed by chemotherapy.

PMID- 29225268
TI  - Lanthanum Deposition in the Stomach in the Absence of Helicobacter pylori
      Infection.
AB  - In this case report, we describe two patients who showed a diffusely whitish
      mucosa in the posterior wall and the lesser curvature of the gastric body. The
      patients were serologically- and histopathologically-negative for Helicobacter
      pylori. Random biopsy specimens from the stomach revealed no regenerative
      changes, intestinal metaplasia, and/or foveolar hyperplasia in either of the
      patients. Although lanthanum deposition in the gastric mucosa has been reported
      to occur in close association with H. pylori-associated gastritis, our patients
      tested negative for H. pylori. These cases suggest that lanthanum deposition
      presents as whitish lesions in the gastric body in H. pylori-negative patients.

PMID- 29225269
TI  - Late Relapse after a Sustained Virologic Response at 24 Weeks after Treatment
      with Daclatasvir and Asunaprevir Combination Therapy for Chronic Hepatitis C
      Virus Genotype 1b Infection with Liver Cirrhosis.
AB  - There have been few studies on relapse after a sustained virological response in
      hepatitis C virus (HCV) patients treated with interferon-free regimens. Thus, the
      risk of late relapse in patients treated with interferon-free therapy remains
      unclear. A 67-year-old woman with HCV genotype 1b and liver cirrhosis received
      oral daclatasvir and asunaprevir. Combination therapy was stopped after 4 weeks
      because of an episode of encephalopathy. Nonetheless, an HCV polymerase chain
      reaction at 24 weeks posttreatment was negative. However, HCV ribonucleic acid
      was detectable at approximately 62 weeks posttreatment. Very late HCV relapses
      may occur in patients with liver cirrhosis who receive an interferon-free regimen
      when the treatment period is insufficient.

PMID- 29225270
TI  - IgA Vasculitis with Simultaneous Cardiopulmonary Involvement.
AB  - A 60-year-old man with a history of hypertension, type 2 diabetes, and reflux
      esophagitis was admitted to our hospital with hemoptysis, dyspnea, and leg edema.
      We diagnosed him with adult IgA vasculitis based on the presence of purpura,
      elevated serum IgA fibronectin complexes, pathophysiological findings, a skin
      biopsy showing leukocytoclastic vasculitis, and immunofluorescence studies
      demonstrating granular IgA and C3 deposits in the blood vessel wall. He showed
      concurrent cardiopulmonary involvement without involvement of the
      gastrointestinal system and kidneys, which are commonly affected in IgA
      vasculitis patients. Following treatment with prednisolone, the patient recovered
      with improvement in cardiopulmonary manifestations.

PMID- 29225271
TI  - Clinical Relapse of Anti-AMPAR Encephalitis Associated with Recurrence of
      Thymoma.
AB  - We report a rare case of anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor (AMPAR) encephalitis presenting clinical relapse in association
      with recurrence of thymoma. Anti-AMPAR encephalitis is an autoimmune-mediated
      neurological disease, frequently accompanied by the presence of neoplasms, thus
      comprising the spectrum of paraneoplastic syndrome. A patient had been in
      remission for 34 months showed clinical relapse 3 months after the detection of
      recurrent thymoma. Clinical relapse of anti-AMPAR encephalitis after the
      recurrence of an initially detected neoplasm has not been previously reported.
      Our case therefore highlights the pathogenic relevance of specific tumor antigens
      as a trigger of anti-AMPAR antibody production and induction of the disease.

PMID- 29225272
TI  - Tumor Emboli from Aortic Metastasis.

PMID- 29225273
TI  - Acquired Long-QT Syndrome: Mild but Abnormal?

PMID- 29225274
TI  - Pseudomelanosis Duodeni and Duodenal Polyp.

PMID- 29225275
TI  - Jackhammer Esophagus Accompanied by Esophageal Intramural Pseudodiverticulosis.

PMID- 29225276
TI  - Mitral Regurgitation and Heart Failure as the First Presentation in a Patient
      with Features of Two Connective Tissue Disorders: A Rare Combination of
      Mucopolysaccharidosis and Osteogenesis Imperfecta?
AB  - Connective tissue disorders sometimes involve cardiovascular systems. This report
      describes the case of a middle-aged man with mitral regurgitation and heart
      failure. He had distinctive features of mucopolysaccharidosis type (MPS) III, but
      no gene mutations that were known to be associated with MPS. Meanwhile, he had a
      COL1A2 gene mutation that is associated with osteogenesis imperfecta (OI), and
      had some features that were compatible with OI. The patient might have had a rare
      connective tissue disorder with the characteristics of MPS III and OI, which was
      initially detected as a result of the cardiovascular manifestations.

PMID- 29225277
TI  - Evaluation of residual monomer release and toxicity of self-adhesive resin
      cements.
AB  - The aim of this study was to evaluate the amount of leached residual monomers
      from self-adhesive resin cements and evaluate their toxicity in-vitro. A total of
      60 disk-shaped specimens (5 mm in diameter and 0.5 mm in thickness) were prepared
      from each cement (RelyX U200, SpeedCEM, G-Cem) (n=20). Specimens were immersed in
      artificial saliva and the amount of released monomers [urethane dimethacrylate
      (UDMA) and triethyleneglycol dimethacrylate (TEGDMA)] was identified. Then, the
      cytotoxicity and genotoxicity effect on cells were evaluated using the defined
      amounts of released monomers from cements. The highest monomer release was
      detected in G-Cem (p<0.05). The highest cytotoxicity value was identified from
      SpeedCEM (p<0.01) and the highest genotoxicity values were calculated from RelyX
      U200 (p<0.05). Released UDMA and TEGDMA from self-adhesive resin cements induced
      cytotoxicity and genotoxicity effect on cells.

PMID- 29225278
TI  - Physiochemical properties and resorption progress of porcine skin-derived
      collagen membranes: In vitro and in vivo analysis.
AB  - The aim of the present study was to evaluate the physiochemical properties and
      resorption progress of two cross-linked, porcine skin-derived collagen membranes
      and compare their features with those of a membrane without cross-linking (Bio
      Gide(r) [BG], Geistlich Biomaterials, Wolhusen, Switzerland). Three porcine skin
      derived collagen membranes, dehydrothermally (DHT) cross-linked (experimental),
      DHT and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (DHT/EDC) cross-linked
      (experimental) and BG were investigated for their morphology, enzyme resistance,
      and tensile strength in vitro and biodegradation in vivo. DHT and DHT/EDC
      membranes exhibited irregular, interconnected macro- and micropores that formed a
      3D mesh, whereas BG exhibited individual collagen fibrils interlaced to form
      coarse collagen strands. In enzyme resistance and tensile strength tests, DHT and
      DHT/EDC membranes demonstrated good resistance and mechanical properties compared
      with BG. In vivo, all three membranes were well integrated into the surrounding
      connective tissue. Thus, the DHT membrane exhibited its potential as a barrier
      membrane for guided bone and tissue regeneration.

PMID- 29225279
TI  - Influence of enamel prism orientations on color shifting at the border of resin
      composite restorations.
AB  - This study aimed to investigate the influence of enamel prism orientations on
      color adjustment of resin composite restoration. The color measurements (L*, C*,
      or h* values) at the restored bovine enamel disk (1.0 mm-thick) with resin
      composite (Estelite Asteria, Estelite Pro, Kalore, Clearfil Majesty) were
      performed using a CIE XYZ camera (RC500). The color shifting rate and range at
      the coronal and cervical border were calculated. The coronal border was
      significantly lower L* and C* color shifting rate than the cervical border
      (p<0.05). The L* color shifting range was significantly affected by regions in
      the 3-mm cavity group (p<0.05), but not in the 1-mm cavity group (p>0.05), while
      the C* color shifting range was not significantly affected by regions (p>0.05).
      The coronal enamel border with diagonal-cut of enamel prisms would have an
      advantage for color adjustment of resin composite restorations compared to the
      cervical border with longitudinal-cut of enamel prisms.

PMID- 29225280
TI  - Quaternary ammonium compounds in dental restorative materials.
AB  - Quaternary ammonium compounds (QACs) have been used widely in medicine, owing to
      their antimicrobial properties. They also have strong permeability, stable
      performance, low skin irritation, low toxicity, low corrosion, lasting biological
      effects and so on, comparing with other antimicrobial agents. At the end of last
      century, polymerizable quaternary ammonium antimicrobial monomers had been
      synthesized and applied in dentistry, in order to reduce or prevent microbial
      biofilm formation on dental materials surfaces. This review aims to discuss the
      current progress of QACs applied in composite resin, adhesive systems, acrylic
      resin, glass ionomer cement and endodontic materials, regarding to their
      antimicrobial potential, mechanical properties, and biocompatibility.

PMID- 29225281
TI  - Effect of electrolyzed water produced using carbon electrodes on HeLa cell
      proliferation.
AB  - We developed electrolyzed water (EW) using carbon electrodes and investigated the
      ability of the developed EW to inhibit the proliferation of human cervical
      carcinoma HeLa cells. We observed that EW-containing media inhibited HeLa cell
      proliferation. Many very small black dots were produced in EW and these were
      associated with the inhibitory effect on the cell proliferation. Furthermore, the
      very small black dots that could inhibit cell proliferation were produced only at
      pH 3 to 3.5 of EW. Additional experiments showed that this inhibition of
      proliferation is reversible. These results suggest that the effect of EW on HeLa
      cells is cytostatic and not cytotoxic. Thus, our results indicate that the EW
      developed in this study may be used to inhibit cell proliretation.

PMID- 29225282
TI  - The impact of population aging on medical expenses: A big data study based on the
      life table.
AB  - This study shed light on the amount and structure of utilization and medical
      expenses on Shanghai permanent residents based on big data, simulated lifetime
      medical expenses through combining of expenses data and life table model, and
      explored the dynamic pattern of aging on medical expenditures. 5 years were taken
      as the class interval, the study collected and did the descriptive analysis on
      the medical services utilization and medical expenses information for all ages of
      Shanghai permanent residents in 2015, simulated lifetime medical expenses by
      using current life table and cross-section expenditure data. The results showed
      that in 2015, outpatient and emergency visits per capita in the elderly group
      (aged 60 and over) was 4.1 and 4.5 times higher than the childhood group (aged 1
      14), and the youth and adult group (aged 15-59); hospitalization per capita in
      the elderly group was 3.0 and 3.5 times higher than the childhood group, and the
      youth and adult group. People survived in the 60-64 years group, their expected
      whole medical expenses (105,447 purchasing power parity Dollar) in the rest of
      their lives accounted for 75.6% of their lifetime. A similar study in Michigan,
      US showed that the expenses of the population aged 65 and over accounted for 1/2
      of lifetime medical expenses, which is much lower than Shanghai. The medical
      expenses of the advanced elderly group (aged 80 and over) accounted for 38.8% of
      their lifetime expenses, including 38.2% in outpatient and emergency, and 39.5%
      in hospitalization, which was slightly higher than outpatient and emergency.
      There is room to economize in medical expenditures of the elderly people in
      Shanghai, especially controlling hospitalization expenses is the key to saving
      medical expenses of elderly people aged over 80 and over.

PMID- 29225283
TI  - Gene cloning and expression of fungal lignocellulolytic enzymes from the rumen of
      gayal (Bos frontalis).
AB  - A total of 6,219 positive clones were obtained by constructing a BAC library of
      uncultured ruminal fungi of gayal, and two clones (xynF1 and eglF2) with
      lignocellulolytic enzyme activity were selected. The sequencing results showed
      that xynF1 and eglF2 had 903-bp, and 1,995-bp, open reading frames likely to
      encode beta-xylanase (XynF1) and beta-glucosidase (EglF2), respectively. The
      amino acid sequence of XynF1 had 99% coverage and 95% homology to the endo-beta
      1,4-xylanase encoded by the cellulase gene of Orpinomyces sp. LT-3 (GenBank
      accession No. AEO51791.1). The amino acid sequence of EglF2 had 99% coverage and
      93% homology to the beta-glucosidase encoded by the cellulase gene of Piromyces
      sp. E2 (GenBank accession No. CAC34952.1). Analysis using the SMART software
      showed that XynF1 contains a glycoside hydrolase family 11 functional module and
      a carbohydrate-binding module, while EglF2 contains a glycoside hydrolase family
      1 functional module. XynF1 showed the highest relative enzymatic activity, up to
      95%, at 45 degrees C and pH 4.2, while EglF2 showed the highest relative
      enzymatic activity, up to 95%, at 55 degrees C and pH 6.2. In this study, we
      achieved efficient expression of the xynF1 and eglF2 genes in Pichia pastoris,
      which laid a foundation for the practical application of the lignocellulolytic
      enzymes.

PMID- 29225284
TI  - Characterization of extracellular matrix components from the desiccation-tolerant
      cyanobacterium Nostoc commune.
AB  - The terrestrial cyanobacterium Nostoc commune forms macroscopic colonies in its
      natural habitats, and these colonies consist of both cellular filaments and
      massive extracellular matrixes. In this study, the biochemical features of the
      extracellular matrix components were investigated. Naturally growing N. commune
      was tolerant to desiccation, and produced massive extracellular polysaccharides
      that contained both neutral sugars and glucuronic acid as constituent
      monosaccharides. The extracellular polysaccharide contents and desiccation
      tolerance were compared in laboratory culture strains of Nostoc species. The
      laboratory culture of N. commune strain KU002 was sensitive to desiccation and
      produced smaller amounts of extracellular polysaccharides, unlike the field
      isolated naturally growing colonies. Nostoc punctiforme strain M-15, which is
      genetically closed to N. commune, was able to tolerate desiccation, although the
      other Nostoc strains were desiccation-sensitive. A laboratory culture strain of
      the aquatic cyanobacterium Nostoc sphaericum produced massive extracellular
      polysaccharides but was sensitive to desiccation, suggesting that extracellular
      matrix production is not enough to make this strain tolerant to desiccation. WspA
      (water stress protein) and SodF (superoxide dismutase) were found to be
      characteristic protein components of the extracellular matrix of N. commune.
      Because the WspA proteins were heterogeneous, the wspA genes were highly diverse
      among the different genotypes of N. commune, although the sodF gene was rather
      conservative. The heterogeneity of the WspA proteins suggests their complex roles
      in the environmental adaptation mechanism in N. commune.

PMID- 29225286
TI  - J. Gen. Appl. Microbiol., 62, 266-271 (2016) doi 10.2323/jgam.2016.04.001.

PMID- 29225285
TI  - Evaluation of probiotic and prebiotic-like effects of Bacillus subtilis BN on
      growth of lactobacilli.
AB  - The aim of this study was to determine the probiotic and the prebiotic-like
      properties of Bacillus subtilis BN, a spore-forming bacterium, also known as
      "natto-kin", which is used for making the Japanese fermented food, natto. We used
      the spores and vegetative cells of this strain and compared their effects on the
      growth of lactobacilli. Culture supernatant from B. subtilis BN was added to a
      glucose-free MRS medium used to culture lactobacilli. When lactobacilli were
      cultured in the supernatant-containing medium, growth was improved. This effect
      resulted from the digestion of starch by amylase, which was secreted by B.
      subtilis. Moreover, improved amylase-independent growth was also observed. Co
      culture with B. subtilis improved the growth of lactobacilli, and this effect was
      only observed with vegetative cells; spores did not improve the growth of
      lactobacilli. This effect on growth was lost upon heat treatment of the
      vegetative cells. These results suggest that the surface protein of B. subtilis
      BN vegetative cells participates in the improved growth effect of lactobacilli.
      It is possible that B. subtilis BN could improve the intestinal flora. In
      addition, B. subtilis BN inhibited the growth of Salmonella enterica. Thus, it
      was shown that B. subtilis BN has both a probiotic and prebiotic potential. This
      is the first study demonstrating the selective growth improvement of indigenous
      intestinal lactobacilli using B. subtilis BN.

PMID- 29225287
TI  - Lysogenisation of Shiga toxin-encoding bacteriophage represses cell motility.
AB  - Bacteriophages are genetic elements that play key roles in the evolution and
      diversification of bacterial genomes. The Shiga toxin (Stx)-encoding phage plays
      an important role in the horizontal transfer of the stx gene. However, the
      influence of the Stx phage integration on the physiological properties and gene
      expression pattern of the host have not been clearly resolved. In this study, we
      constructed the Sp5 lysogen through lysogenisation of E. coli K-12 by Sp5, an
      Stx2 phage in enterohaemorrhagic E. coli (EHEC) O157:H7 Sakai, and examined the
      effect of the resulting lysogen on cell motility under various growth conditions.
      Sp5 lysogenisation decreased cell motility and the expression of fliC, which
      encodes flagellin, under anaerobic conditions at 37 degrees C. Sp5 also lowered
      the expression of fliA, which encodes the FliA-sigma factor responsible for the
      transcription of fliC, and flhD, which facilitates the expression of fliA. Sp5
      lysogenisation reduced the amount of FlhD and FlhC expressed from the araBAD
      promoter, suggesting that one or more genes present in Sp5 represses flhDC at the
      post-transcriptional level. Flagellin is highly antigenic and triggers an immune
      response in the host. Thus, Sp5 might enhance its viability by repressing the
      expression of the flagellar regulon to circumvent the immune response of host
      cells.

PMID- 29225288
TI  - [Microglia and cellular differentiation - possibility of microglia as drug
      discovery target].

PMID- 29225289
TI  - [Heart repair using direct cardiac reprogramming].

PMID- 29225290
TI  - [Neural differentiation from induced pluripotent stem cells for disease modelling
      and drug discovery].

PMID- 29225291
TI  - [Novel function of axon guidance molecule as a regulator of tumor
      microenvironment].

PMID- 29225292
TI  - [Experimental techniques for animal models of retinal vein occlusion in mice].

PMID- 29225293
TI  - [Involvement of G-quadruplexes in neurodegenerative diseases].

PMID- 29225294
TI  - [Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 37, Number 11,
      November 25, 2017].

PMID- 29225295
TI  - Effect of Smoking Status on Monocyte Tissue Factor Activity, Carotid
      Atherosclerosis and Long-Term Prognosis in Metabolic Syndrome.
AB  - BACKGROUND: Smoking increases the risk of atherothrombotic events. Tissue factor
      (TF) mainly expressed on monocytes plays an important role in thrombosis and
      atherosclerosis. Metabolic syndrome (MetS) is being increasingly recognized as a
      major atherothrombotic risk factor, but the effects of smoking on monocyte TF
      activity (MTFA), carotid atherosclerosis estimated on carotid intima-media
      thickness (CIMT), and long-term prognosis in MetS remain unclear.Methods and
      Results:A total of 301 MetS patients lacking any known cardiovascular disease
      were prospectively investigated and classified into 4 groups according to smoking
      status at entry and at 12 months as follows: never smokers, past smokers,
      quitters, and persistent smokers. Peripheral blood mononuclear cells (PBMC) were
      isolated, and MTFA was measured using a coagulation assay. Linear trends for
      higher baseline MTFA and CIMT were observed among persistent smokers, quitters,
      and past smokers compared with never smokers. At 12 months, MTFA and CIMT
      decreased in never and past smokers and quitters but increased in persistent
      smokers. Six acute myocardial infarctions and 8 strokes occurred during a median
      follow-up of 66.0 months. Persistent smoking was associated with an increased
      risk of events (P<0.001). CONCLUSIONS: Smoking is associated with upregulated
      MTFA and progression of CIMT, which may be related to the risk of
      atherothrombotic events in MetS patients.

PMID- 29225296
TI  - Who Will Achieve Stable Anticoagulation Therapy With Warfarin?

PMID- 29225297
TI  - Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine
      Population-Based Cohort Studies With More Than 340,000 Japanese Subjects.
AB  - BACKGROUND: A high body mass index (BMI) has been proposed as an important risk
      factor for pancreatic cancer. However, this association of BMI with pancreatic
      cancer risk has not been confirmed in Asian populations. METHODS: We evaluated
      the association between BMI (either at baseline or during early adulthood) and
      pancreatic cancer risk by conducting a pooled analysis of nine population-based
      prospective cohort studies in Japan with more than 340,000 subjects. Summary
      hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI
      categories with a random-effects model. RESULTS: Among Japanese men, being obese
      at baseline was associated with a higher risk of pancreatic cancer incidence
      (>=30 kg/m2 compared with 23 to <25 kg/m2, adjusted HR 1.71; 95% confidence
      interval [CI], 1.03-2.86). A J-shaped association between BMI during early
      adulthood and pancreatic cancer incidence was seen in men. In contrast, we
      observed no clear association among women, although there may be a positive
      linear association between BMI at baseline and the risk of pancreatic cancer (per
      1 kg/m2, adjusted HR 1.02; 95% CI, 1.00-1.05). CONCLUSIONS: Pooling of data from
      cohort studies with a considerable number of Japanese subjects revealed a
      significant positive association between obesity and pancreatic cancer risk among
      men. This information indicates that strategies that effectively prevent obesity
      among men might lead to a reduced burden of pancreatic cancer, especially in
      Asian populations.

PMID- 29225299
TI  - Predictors of a Persistent Status of Pulmonary Vein Electrical Isolation by a
      Cryoballoon Application for Drug-Refractory Atrial Fibrillation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) using a cryoballoon (CB) is utilized
      for treating atrial fibrillation. This study aimed to assess the effect of the
      procedural characteristics of CB-based PVI (CB-PVI) on late PV
      reconnections.Methods and Results:A total of 389 consecutive patients underwent
      the CB-PVI as their index procedure; 45 consecutive patients underwent re-do
      procedures (184+/-87 days after the index CB-PVI). A total of 146 of 178 PVs
      (82%) remained isolated. The occlusion grade was evaluated in 171 PVs. Complete
      PV occlusion by the CB (grade 4) was obtained in 122 of 171 PVs (71%) during the
      index CB-PVI and the PVI status was maintained in 111 PVs (91%). Among the
      remaining 49 CB-PVIs without complete PV occlusion (grades 1-3), 20 PVs (41%) had
      late PV reconnections despite successful PVI during the index CB-PVI. A "pull
      down maneuver" was performed in 20 PVs because of leakage of blood at the
      inferior aspect of the PVs, and all those PVs with a successful pull-down
      maneuver maintained their PVI status. A multivariate analysis demonstrated that
      the presence of complete PV occlusion was the only independent predictor for
      persistence of PVI. CONCLUSIONS: The occlusion grade was a reliable predictor of
      the long-term durability of PVI.

PMID- 29225298
TI  - Long-term Impact of Cardiorespiratory Fitness on Type 2 Diabetes Incidence: A
      Cohort Study of Japanese Men.
AB  - BACKGROUND: We sought to examine the association between cardiorespiratory
      fitness (CRF) and incidence of type 2 diabetes considering the follow-up period
      in a cohort of Japanese men with a maximum follow-up period of 23 years. METHODS:
      This study enrolled 7,804 male workers free of diabetes in 1986. CRF was measured
      using a cycle ergometer, and maximal oxygen uptake was estimated. During 1986
      2009, participants were followed for development of type 2 diabetes, which was
      diagnosed using fasting blood tests, self-administered questionnaires, or oral
      glucose tolerance tests after urinary tests from annual health checkups. Hazard
      ratios for the incidence of type 2 diabetes were estimated using Cox proportional
      hazards models. RESULTS: During the follow-up period, 1,047 men developed type 2
      diabetes. In analyses by follow-up periods (1986-1993, 1994-2001, and 2002-2009),
      there was an inverse dose-response relationship between CRF and the development
      of type 2 diabetes for all three follow-up periods (P for trend 0.019, <0.001,
      and 0.001, respectively), and the association between CRF at baseline and the
      incidence of type 2 diabetes did not weaken with longer follow-up period.
      Compared with the lowest CRF group, hazard ratios of developing type 2 diabetes
      were 0.69 (95% confidence interval [CI], 0.49-0.97) for the highest CRF group in
      1986-1993, 0.57 (95% CI, 0.42-0.79) for the highest CRF in 1994-2001, and 0.47
      (95% CI, 0.30-0.74) for the highest CRF in 2002-2009. CONCLUSION: High CRF is
      associated with a lower risk of the incidence of type 2 diabetes over an extended
      period of >20 years among men.

PMID- 29225300
TI  - Metabolomic Analysis in Heart Failure.
AB  - It is thought that at least 6,500 low-molecular-weight metabolites exist in
      humans, and these metabolites have various important roles in biological systems
      in addition to proteins and genes. Comprehensive assessment of endogenous
      metabolites is called metabolomics, and recent advances in this field have
      enabled us to understand the critical role of previously unknown metabolites or
      metabolic pathways in the cardiovascular system. In this review, we will focus on
      heart failure and how metabolomic analysis has contributed to improving our
      understanding of the pathogenesis of this critical condition.

PMID- 29225301
TI  - Paralysis of the Rectus Abdominis Muscle after a Video-Assisted Thoracoscopic
      Surgery.
AB  - The rectus abdominis muscle is innervated by intercostal nerves T7-T12, and most
      thoracotomies are performed through the fourth to sixth intercostal spaces, so
      direct nerve damage to the rectus abdominis seems unlikely. However, at least one
      trocar is inserted below the seventh intercostal space in most multi-port video
      assisted thoracoscopic surgeries (VATSs), and injury of the seventh or lower
      intercostal nerve with related paralysis of the rectus abdominis is possible,
      albeit rare. Only two cases of rectus abdominis paralysis caused by after VATSs
      have been reported, and these cases were not permanent injuries. This is the
      first report of permanent paralysis of the rectus abdominis after VATSs.

PMID- 29225302
TI  - Role of Surgery in the Treatment of Masaoka Stage IVa Thymoma.
AB  - PURPOSE: To analyze the role of surgery in patients with Masaoka stage IVa
      thymoma treated with multimodality therapy. METHODS: Of 191 patients undergoing
      surgery for thymoma in our department between January 2002 and December 2015, 39
      (20.4%) had Masaoka stage IVa. Histopathological tumor type, myasthenic status of
      the Osserman-Genkins score, Masaoka stage at the first surgery, neoadjuvant
      treatment, number and type of surgeries, and survival rates were recorded.
      RESULTS: Thymoma B2 was the most common histopathological tumor type (n = 16,
      41%). Twenty-six (66.7%) patients underwent primary surgeries for Masaoka stage
      IVa thymoma, whereas nine (23.1%) underwent secondary surgeries and four (10.3%)
      underwent tertiary surgeries for pleural or pericardial recurrences. Median
      survival was 132 +/- 25 (82-181; 95% confidence interval [CI]) months. Overall 3
      , 5-, and 10-year survival rates were 93%, 93%, and 56%, respectively.
      CONCLUSION: Surgical treatment should be considered as a completion modality to
      oncological therapy and has the potential to provide long-term survival of
      Masaoka stage IVa in patients with thymoma. The type of surgery should be
      determined based on the invasiveness of the lesion.

PMID- 29225303
TI  - Evaluation of heat stress response in crossbred dairy cows under tropical climate
      by analysis of heart rate variability.
AB  - The present study aims to examine the effect of tropical temperatures on
      autonomic nervous activity in Cambodian dairy cattle by analyzing heart rate
      variability (HRV). Holter-type electrocardiograms were recorded in adult
      crossbred cows (Cambodian native * Holstein) either in a sheltered area or under
      direct sunlight. Rectal temperatures and heart rates increased in animals under
      direct sunlight as compared to those in the shelter. The power spectral analysis
      of HRV revealed that three out of the five cows studied underwent a decrease in
      parasympathetic nervous activity under direct sunlight with the remaining two
      cows showing no apparent change. The HRV analysis would prove to be a useful tool
      to reveal information about heat tolerance in dairy cows.

PMID- 29225304
TI  - Investigation of the synergistic effects of haloperidol combined with Calculus
      Bovis Sativus in treating MK-801-induced schizophrenia in rats.
AB  - Clinical studies that focused on treating schizophrenia showed that Calculus
      Bovis Sativus (CBS), a substitute of Calculus Bovis, when used in combination
      with haloperidol could significantly lower the dosage of haloperidol compared
      with treatment with haloperidol alone, whereas efficacy was maintained. The aim
      of this study was to investigate the synergetic anti-schizophrenia effects in
      rats using CBS in combination with haloperidol. An open field test was conducted
      to verify the pharmacodynamic effects of a combination treatment of CBS and
      haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of
      intragastric haloperidol and intravenous haloperidol were determined after oral
      administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg).
      The pharmacodynamic data showed a significant decrease in locomotor activity and
      an increase in the percentage of the central distance when haloperidol was
      concomitantly administered with CBS compared with haloperidol administration
      alone. The AUC0-infinity and Cmax of haloperidol in the orally coadministered
      groups were significantly higher compared with the oral treatment with
      haloperidol alone. In conclusion, oral coadministration of CBS with haloperidol
      resulted in a synergistic effect in rats. The enhanced oral bioavailability of
      haloperidol when combined with CBS might be attributed to the interaction between
      them.

PMID- 29225305
TI  - The past, present, and future of disease-modifying therapies for Alzheimer's
      disease.
AB  - The development of disease-modifying therapies for Alzheimer's disease (AD) is an
      urgent issue. Progress in the understanding of AD pathophysiology based on the
      amyloid hypothesis has led to the development of numerous candidate disease
      modifying therapies over the past 15 years. The therapeutic target, amyloid beta
      (Abeta), starts to accumulate in AD brains long before the onset of cognitive
      decline. gamma-secretase inhibitors, gamma-secretase modulators, and beta
      secretase inhibitors aim to reduce the production of toxic Abeta species by
      modifying the processing of amyloid precursor protein. Another strategy is to
      eliminate accumulated Abeta by active or passive immunotherapeutic approaches.
      Therapeutic strategies targeting tau protein are also currently emerging. Despite
      these efforts, successful disease-modifying therapies for AD have not yet been
      developed. Recently, very early interventional trials targeting preclinical
      stages of AD have begun; the paradigm shift in AD therapies from cure to
      prevention could be key to the success of disease modification.

PMID- 29225308
TI  - Evaluation of radioactivity in the bodies of mice induced by neutron exposure
      from an epi-thermal neutron source of an accelerator-based boron neutron capture
      therapy system.
AB  - This study aimed to evaluate the residual radioactivity in mice induced by
      neutron irradiation with an accelerator-based boron neutron capture therapy
      (BNCT) system using a solid Li target. The radionuclides and their activities
      were evaluated using a high-purity germanium (HP-Ge) detector. The saturated
      radioactivity of the irradiated mouse was estimated to assess the radiation
      protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr,
      82Br, 56Mn, and 42K were identified, and their saturated radioactivities were
      (1.4 +/- 0.1) * 102, (2.2 +/- 0.1) * 101, (3.4 +/- 0.4) * 102, 2.8 +/- 0.1, 8.0
      +/- 0.1, and (3.8 +/- 0.1) * 101 Bq/g/mA, respectively. The 24Na activation rate
      at a given neutron fluence was found to be consistent with the value reported
      from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide
      can be estimated by entering the saturated activity of each nuclide, sample mass,
      irradiation time, and proton current into the derived activation equation in our
      accelerator-based BNCT system.

PMID- 29225306
TI  - What do eye movements tell us about patients with neurological disorders? - An
      introduction to saccade recording in the clinical setting.
AB  - Non-invasive and readily implemented in the clinical setting, eye movement
      studies have been conducted extensively not only in healthy human subjects but
      also in patients with neurological disorders. The purpose of saccade studies is
      to "read out" the pathophysiology underlying neurological disorders from the
      saccade records, referring to known primate physiology. In the current review, we
      provide an overview of studies in which we attempted to elucidate the patterns of
      saccade abnormalities in over 250 patients with neurological disorders, including
      cerebellar ataxia and brainstem pathology due to neurodegenerative disorders, and
      what they tell about the pathophysiology of patients with neurological disorders.
      We also discuss how interventions, such as deep brain stimulation, affect saccade
      performance and provide further insights into the workings of the oculomotor
      system in humans. Finally, we argue that it is important to understand the
      functional significance and behavioral correlate of saccade abnormalities in
      daily life, which could require eye tracking methodologies to be performed in
      settings similar to daily life.

PMID- 29225309
TI  - Cell size for commitment to cell division and number of successive cell divisions
      in multicellular volvocine green algae Tetrabaena socialis and Gonium pectorale.
AB  - Volvocine algae constitute a green algal lineage comprising unicellular
      Chlamydomonas, four-celled Tetrabaena, eight to 32-celled Gonium, and others up
      to Volvox spp., which consist of up to 50,000 cells. These algae proliferate by
      multiple fissions with cellular growth up to several fold in size and subsequent
      successive cell divisions. Chlamydomonas reinhardtii cells produce two to 32
      daughter cells by one to five divisions, depending on cellular growth in the G1
      phase. By contrast, in this study, we found that Tetrabaena socialis and Gonium
      pectorale cells mostly produced four and eight daughter cells by two and three
      successive divisions, respectively. In contrast to C. reinhardtii, which is
      committed to cell division when the cell has grown two-fold, T. socialis and G.
      pectorale are committed only when the cells have grown four- and eight-fold,
      respectively. Thus, our results suggest that evolutionary changes in cellular
      size for commitment largely contributes to the emergence and evolution of
      multicellularity in volvocine algae.

PMID- 29225310
TI  - Molecular chirality: A new approach from a dynamical point of view.
AB  - The double minimum potential (DMP), which Hund assumed to explain the quantum
      mechanical stability of enantiomers, was discussed, by citing three typical
      examples of DMP: inversion, internal rotation, and puckering. They expanded the
      classical scope of chirality, as defined by Kelvin, and indicated that a new
      bridge could be formed between the three low-frequency DMP modes and the
      asymmetric syntheses of chiral molecules.

PMID- 29225307
TI  - Millisecond Ca2+ dynamics activate multiple protein cascades for synaptic vesicle
      control.
AB  - For reliable transmission at chemical synapses, neurotransmitters must be
      released dynamically in response to neuronal activity in the form of action
      potentials. Stable synaptic transmission is dependent on the efficacy of
      transmitter release and the rate of resupplying synaptic vesicles to their
      release sites. Accurate regulation is conferred by proteins sensing Ca2+ entering
      through voltage-gated Ca2+ channels opened by an action potential. Presynaptic
      Ca2+ concentration changes are dynamic functions in space and time, with wide
      fluctuations associated with different rates of neuronal activity. Thus,
      regulation of transmitter release includes reactions involving multiple Ca2+
      dependent proteins, each operating over a specific time window. Classically,
      studies of presynaptic proteins function favored large invertebrate presynaptic
      terminals. I have established a useful mammalian synapse model based on
      sympathetic neurons in culture. This review summarizes the use of this model
      synapse to study the roles of presynaptic proteins in neuronal activity for the
      control of transmitter release efficacy and synaptic vesicle recycling.

PMID- 29225311
TI  - Inhibition of Oxidative Stress by Antioxidant Supplementation Does Not Limit
      Muscle Mitochondrial Biogenesis or Endurance Capacity in Rats.
AB  - The objective of the present study was to analyze the activation and expression
      patterns of upstream and downstream factors of PGC-1alpha to determine whether
      antioxidant (AO) supplementation inhibits mitochondrial biogenesis in skeletal
      muscles as an adaptation to endurance training, as well as to analyze changes in
      endurance capacity based on such findings. For this objective, 24 male Sprague
      Dawley (SD) rats were allocated into 4 groups (vehicle-sedentary, V-Sed; vehicle
      exercise, V-EX; antioxidant-sedentary, AO-Sed; antioxidant-exercise, AO-EX) of 6
      rats each. The rats were then treated with vitamin C (500 mgkg-1 body weightd-1)
      or a placebo for 8 wk, and a swimming program was implemented in some rats during
      the last 4 wk of this period. Immediately after the last training session, blood
      was collected from the tail of each rat, and TBARS was measured to test the
      effect of vitamin C as an AO. As a result, increased oxidative stress from
      exercise was inhibited by vitamin C supplementation. Analysis of whether reduced
      oxidative stress by vitamin C supplementation also inhibited mitochondrial
      biogenesis within skeletal muscles showed that phosphorylation of p38 MAPK and
      AMPK, along with levels of PGC-1alpha, NRF-1, mtTFA, and mitochondrial electron
      transport enzymes, increased after endurance training in spite of vitamin C
      supplementation. Moreover, running time, distance, and total work increased
      significantly in the exercise group as compared to those in the sedentary group,
      regardless of vitamin C supplementation. These results indicate that
      mitochondrial biogenesis and endurance capacity increase as a result of endurance
      training, regardless of AO supplementation.

PMID- 29225312
TI  - Prevalence and Trends of Vitamin D Deficiency among Iranian Adults: A
      Longitudinal Study from 2001-2013.
AB  - Vitamin D deficiency/insufficiency is currently considered to be a re-emerging
      public health problem globally. This study was designed to determine the
      prevalence of vitamin D deficiency and insufficiency and to investigate its trend
      from 2001 to 2013 in a longitudinal study of Iranian adults. This study was part
      of a population-based, longitudinal ongoing study of Iranian healthy adults aged
      35 y and older at baseline. Serum vitamin D level was assessed in a sub-sample of
      370 subjects, who were apparently healthy at the time of recruitment in 2001 and
      were free from MetS, in three phases (2001, 2007 and 2013) during the 12-y study
      period. Adjusted prevalence and trend of vitamin D deficiency were calculated.
      Mean serum vitamin D levels increased over the time of the study (52.12, 54.27
      and 62.28 nmol/L, respectively) and the prevalence of vitamin D deficiency
      decreased (30.5, 27.0 and 24.4, respectively). However, the prevalence of vitamin
      D insufficiency did not change over this time period. The risk of vitamin D
      deficiency decreased significantly in 2007 [OR: 0.73 (95% CI: 0.53, 0.99)] and
      2013 [OR: 0.50 (95% CI: 0.36, 0.70)] compared to the baseline. The present study
      demonstrated some improvement in serum vitamin D levels, while the prevalence of
      vitamin D inadequacy was still high. Considering the possible health consequences
      of vitamin D deficiency, there is an urgent need for developing population-wide
      strategies, such as supplementation and fortification, to prevent or control
      vitamin D deficiency.

PMID- 29225313
TI  - Ingestion of Coffee Polyphenols Improves a Scaly Skin Surface and the Recovery
      Rate of Skin Temperature after Cold Stress: A Randomized, Controlled Trial.
AB  - Coffee polyphenols (CPPs) derived from coffee beans have beneficial effects on
      blood pressure and vascular endothelial function. In addition, CPPs suppress
      ultraviolet light induced erythema. However, the effects of CPPs on dry skin and
      cutaneous vascular function have not been clarified. We investigated the effects
      of CPPs on dry skin and the recovery rate (RR) of skin temperature after a cold
      stress test as a measure of vascular function in subjects with visible scaliness
      in a double-blind, placebo-controlled, randomized study. The subjects were
      divided into two groups, the CPP group and the Placebo group. In the CPP group,
      the subjects ingested a beverage containing 297.8 mg CPPs every day for 4 wk. The
      degree of skin dryness was assessed quantitatively using a Visioscan to evaluate
      skin scaliness and smoothness. A subjective evaluation using a visual analog
      scale (VAS) of skin smoothness was also used. As a result, the scaliness and
      smoothness of cheek skin was significantly improved after 4 wk in the CPP group
      compared to the Placebo group. The improvements of the VAS score on 'skin
      smoothness' and the RR were also observed in the CPP group but the difference was
      not statistically significant. However, when the CPP group was divided into
      subgroups of high RR and low RR, the improvement of the RR was significant in the
      low RR subgroup. In conclusion, our results suggest that CPPs improve skin
      scaliness and play a role in cutaneous blood flow regulation after cold stress.

PMID- 29225314
TI  - Validity and Reliability of a General Nutrition Knowledge Questionnaire for
      Japanese Adults.
AB  - Nutrition knowledge is necessary for individuals to adopt appropriate dietary
      habits, and needs to be evaluated before nutrition education is provided.
      However, there is no tool to assess general nutrition knowledge of adults in
      Japan. Our aims were to determine the validity and reliability of a general
      nutrition knowledge questionnaire for Japanese adults. We developed the pilot
      version of the Japanese general nutrition knowledge questionnaire (JGNKQ) and
      administered the pilot study to assess content validity and internal reliability
      to 1,182 Japanese adults aged 18-64 y. The JGNKQ was further modified based on
      the pilot study and the final version consisted of 5 sections and 147 items. The
      JGNKQ was administered to female undergraduate Japanese students in their senior
      year twice in 2015 to assess construct validity and test-retest reliability.
      Ninety-six students majoring in nutrition and 44 students in other majors who
      studied at the same university completed the first questionnaire. Seventy-five
      students completed the questionnaire twice. The responses from the first
      questionnaire and both questionnaires were used to assess construct validity and
      test-retest reliability, respectively. The students in nutrition major had
      significantly higher scores than the students in other majors on all sections of
      the questionnaire (p=0.000); therefore, the questionnaire had good construct
      validity. The test-retest reliability correlation coefficient value of overall
      and each section except "The use of dietary information to make dietary choices"
      were 0.75, 0.67, 0.67, 0.68 and 0.61, respectively. We suggest that the JGNKQ is
      an effective tool to assess the nutrition knowledge level of Japanese adults.

PMID- 29225315
TI  - Comparison of the Effects of Three Tea Cultivars (Camellia sinensis L.) on Nitric
      Oxide Production and Aortic Soluble Guanylate Cyclase Expression in High-Salt
      Diet-Fed Spontaneously Hypertensive Rats.
AB  - Studies have suggested that the consumption of green tea reduces the risk of
      cardiovascular diseases. Although epigallocatechin gallate (EGCG) is the best
      studied active substance characteristic of green tea, previous results on EGCG do
      not appear sufficient to explain completely the mechanism of cardiovascular
      protection by green tea. Therefore, we investigated the effect of three different
      tea cultivars, "Yabukita," "Sofu," and "Sunrouge," which have characteristic
      flavonoid compositions, on the nitric oxide (NO) production and the related
      protein expression in the aorta of spontaneously hypertensive rats (SHRs) fed a
      high-salt diet. As a result, the reduction of urinary NO metabolite (NOx) levels,
      which reflect whole-body NO production, caused by the high-salt diet were
      significantly prevented by all three tea infusions. The improvement of NOx
      reduction in the tea-intake groups was unlikely to be caused by the changes in
      oxidative damage. On the other hand, as a partial effect, only "Yabukita" or
      "Sofu" increased the expression of the soluble guanylate cyclase, a receptor for
      NO, in the thoracic aorta. In the present study, the differences in the
      composition of these three cultivars led to partially different effects on NO
      signaling in SHRs, suggesting the physiological significance of subdominant
      ingredients besides EGCG.

PMID- 29225316
TI  - Milk Basic Protein Facilitates Increased Bone Mass in Growing Mice.
AB  - Milk basic protein (MBP) comprises a group of basic whey proteins and is
      effective in preventing bone loss by promoting bone deposition (bone formation)
      and suppressing withdrawn (bone resorption). We previously revealed the bone
      protective effects of MBP during life phases involving excessive bone resorption,
      such as in adults and postmenopausal women, and in animal models (ovariectomized
      rats and mice). However, it was unclear whether MBP increases bone mass during
      the growth stage, when there is more bone formation than resorption. We therefore
      investigated the effect of MBP supplementation on bone mass in 6-wk-old mice
      provided water supplemented with MBP [0.01%, 0.1%, 1.0% (w/w)] or deionized water
      (control) ad libitum for 10 wk. Analysis by micro-computerized tomography showed
      that MBP significantly increased tibia cortical bone mineral density and femur
      trabecular bone volume to tissue volume compared with mice provided deionized
      water. Next, the function of MBP in bone remodeling (bone formation and
      resorption) was evaluated using an in vitro system and the results demonstrated
      that MBP directly promoted osteoblast proliferation and inhibited
      osteoclastogenesis. Moreover, the plasma level of insulin-like growth factor-1
      was increased by MBP supplementation, suggesting that MBP indirectly promoted
      osteoblast proliferation/differentiation. These effects enhance bone formation
      and/or inhibit bone resorption, resulting in increased bone mass in growing mice.

PMID- 29225317
TI  - Pre-Exercise High-Fat Diet for 3 Days Affects Post-Exercise Skeletal Muscle
      Glycogen Repletion.
AB  - Previous studies have shown that the short-term intake of a high-fat diet (HFD)
      impairs glucose metabolism. In this study, we investigated the influences of pre
      exercise HFD intake for 3 d on post-exercise glycogen repletion in skeletal
      muscle in ICR mice. Mice received either an HFD (57% kcal from fat, 23% kcal from
      carbohydrate; HFD group) or standard laboratory chow (13% kcal from fat, 60% kcal
      from carbohydrate; Con group) for 3 d before exercise. Mice performed treadmill
      running at 25 m/min for 60 min and were orally administered a glucose (2 mg/g
      body weight) solution immediately after and at 60 min after exercise. A negative
      main effect of pre-exercise HFD intake was observed for skeletal muscle glycogen
      concentration from the pre-exercise phase to 120 min of post-exercise recovery
      (p<0.01). Blood glucose concentration in the HFD group was significantly higher
      than in the Con group at 120 min after exercise (p<0.01). No significant
      difference was observed in plasma insulin concentration. There were no
      significant between-group differences in the phosphorylation state of Akt Thr308,
      AMPK Thr172, AS160 Thr642, or glycogen synthase Ser641 or in glucose transporter
      4 protein levels during post-exercise recovery. Our results suggest that the
      intake of a pre-exercise HFD for 3 d affects post-exercise glycogen repletion in
      skeletal muscle without impairing the insulin signaling cascade.

PMID- 29225318
TI  - Caffeine-Stimulated Intestinal Epithelial Cells Suppress Lipid Accumulation in
      Adipocytes.
AB  - Caffeine is a methylxanthine derived from plant foods such as coffee beans and
      tea leaves, and has multiple biological activities against physiological response
      and several diseases. Although there are some reports about the direct effect of
      caffeine against anti-lipid accumulation in vitro, the effect of caffeine on
      lipid accumulation in adipocytes through stimulating intestinal epithelial cells
      is unknown. Since direct treatment with caffeine to 3T3-L1 cells did not affect
      lipid accumulation, we determined whether caffeine-stimulated intestinal
      epithelial Caco-2 cells influence the lipid accumulation in 3T3-L1 adipocytes.
      Caco-2 cells were cultured on a transwell insert with or without caffeine for 24
      h. Subsequently, the basolateral component of the Caco-2 cell culture on the
      transwell was collected and termed caffeine-conditioning medium (CCM). When 3T3
      L1 adipocytes were incubated with CCM, CCM decreased lipid accumulation and
      suppressed gene expression of proliferator activated receptor (PPAR) gamma and
      CCAAT/enhancer binding protein (C/EBP) alpha in 3T3-L1 adipocytes. Furthermore,
      CCM decreased the expression of C/EBPbeta and C/EBPdelta at the protein level,
      but not at the mRNA level. We observed that a proteasome inhibitor, MG132,
      inhibited CCM-caused down-expression of C/EBPbeta and C/EBPdelta proteins, and
      that CCM promoted the ubiquitination level of C/EBPbeta and C/EBPdelta proteins.
      Protein microarray analysis showed caffeine suppresses the secretion of
      inflammatory cytokines, interleukin-8 and plasminogen activator inhibitor-1 from
      Caco-2 cells. These results suggest that caffeine indirectly suppresses lipid
      accumulation in 3T3-L1 adipocytes through decreasing secretion of inflammatory
      cytokines from Caco-2 cells.

PMID- 29225319
TI  - Effects of Aerobic Exercise Combined with Panaxatriol Derived from Ginseng on
      Insulin Resistance and Skeletal Muscle Mass in Type 2 Diabetic Mice.
AB  - Insulin resistance reduces insulin-induced muscle protein synthesis and
      accelerates muscle protein degradation. Ginseng ingestion has been reported to
      improve insulin resistance through the phosphoinositide 3-kinase (PI3K)/Akt
      signaling pathway. We hypothesized that panaxatriol (PT) derived from ginseng in
      combination with aerobic exercise (EX) may further promote protein synthesis and
      suppress protein degradation, and subsequently maintain muscle mass through the
      amelioration of insulin resistance. KKAy insulin-resistant mice were divided into
      control, panaxatriol only (PT), exercise only (EX), and EX+PT groups. EX and
      EX+PT ran on the treadmill for 45 min at 15 m/min 5 d/wk for 6 wk. PT and EX+PT
      groups were fed a standard diet containing 0.2% PT for 6 wk. Homeostasis model
      assessment for insulin resistance (HOMA-R) values was significantly improved
      after exercise for 6 wk. Moreover, EX+PT mice showed improved HOMA-R as compared
      to EX mice. p70S6K phosphorylation after a 4 h fast was significantly higher in
      EX than in the non-exercise control, and it was higher in EX+PT mice than in EX
      mice. Atrogin1 mRNA expression was significantly lower in EX than in the non
      exercise control, and was significantly lowered further by PT treatment. EX and
      EX+PT mice showed higher soleus muscle mass and cross-sectional area (CSA) of the
      soleus myofibers than control animals, with higher values noted for both
      parameters in EX+PT than in EX. These results suggest that aerobic exercise and
      PT ingestion may contribute to maintain skeletal muscle mass through the
      amelioration of insulin resistance.

PMID- 29225321
TI  - Errata.

PMID- 29225320
TI  - Combination Effect of delta-Tocotrienol and gamma-Tocopherol on Prostate Cancer
      Cell Growth.
AB  - Tocotrienols (T3s) and tocopherols (Tocs) are both members of the vitamin E
      family. It is known that delta-tocotrienol (delta-T3) has displayed the most
      potent anti-cancer activity amongst the tocotrienols. On the other hand, gamma
      tocopherol (gamma-Toc) is reported to have a protective effect against prostate
      cancer. Therefore, we investigated whether the combination of gamma-Toc and delta
      T3 could strengthen the inhibitory effect of delta-T3 on prostate cancer cell
      growth. In this study the effect of combined delta-T3 (annatto T3 oil) and gamma
      Toc (Tmix, gamma-Toc-rich oil) therapy was assessed against human androgen
      dependent prostate cancer cells (LNCaP). We found that combined treatment of
      delta-T3 (10 MUM) and gamma-Toc (5 MUM) resulted in reinforced anti-prostate
      cancer activity. Specifically, cell cycle phase distribution analysis revealed
      that in addition to G1 arrest caused by the treatment with delta-T3, the
      combination of delta-T3 with gamma-Toc induced G2/M arrest. Enhanced induction of
      apoptosis by the combined treatment was also observed. These findings indicate
      that combination of delta-T3 and gamma-Toc significantly inhibits prostate cancer
      cell growth due to the simultaneous cell cycle arrest in the G1 phase and G2/M
      phase.

PMID- 29225322
TI  - Immunohistochemical study on the secretory host defense system with lysozyme and
      secretory phospholipase A2 throughout rat respiratory tract.
AB  - The host defense system with lysozyme and secretory phospholipase A2 (sPLA2) was
      immunohistochemically investigated in rat respiratory tract under healthy
      conditions. In the nasal epithelium, a large number of non-ciliated and non
      microvillous cells (NC) and a small number of goblet cells (GC) were
      immunopositive for lysozyme and sPLA2. A few acinar cells and almost all
      epithelial cells of intercalated ducts were immunopositive for both bactericidal
      substances in the nasal glands. In the laryngeal and tracheal epithelia, few NC
      and GC were immunopositive for both bactericidal substances. In the laryngeal and
      tracheal glands, a few acinar cells and most ductal epithelial cells were
      immunopositive for both bactericidal substances. In extra-pulmonary bronchus,
      small numbers of NC and GC were immunopositive for lysozyme and sPLA2, whereas
      few NC and no GC were immunopositive in the intra-pulmonary bronchus. No
      secretory source of either bactericidal substance was located in the bronchioles.
      In the alveolus, many glandular epithelial cells and alveolar macrophages were
      immunopositive for lysozyme but immunonegative for sPLA2. Moreover, lysozyme and
      sPLA2 were detected in the mucus layer and in the periciliary layer from the nose
      to the extra-pulmonary bronchus. These findings suggest that secretory sources of
      lysozyme and sPLA2 are distributed in almost all the respiratory tract. Their
      secretory products are probably transported to the pharynx and contribute to form
      the first line of defense against inhaled bacteria throughout the respiratory
      tract.

PMID- 29225323
TI  - Mancozeb impairs the ultrastructure of mouse granulosa cells in a dose-dependent
      manner.
AB  - Mancozeb, an ethylene bis-dithiocarbamate, is widely used as a fungicide and
      exerts reproductive toxicity in vivo and in vitro in mouse oocytes by altering
      spindle morphology and impairing the ability to fertilize. Mancozeb also induces
      a premalignant status in mouse granulosa cells (GCs) cultured in vitro, as
      indicated by decreased p53 expression and tenuous oxidative stress. However, the
      presence and extent of ultrastructural alterations induced by mancozeb on GCs in
      vitro have not yet been reported. Using an in vitro model of reproductive
      toxicity, comprising parietal GCs from mouse antral follicles cultured with
      increasing concentrations of mancozeb (0.001-1 ug/ml), we sought to ascertain the
      in vitro ultrastructural cell toxicity by means of transmission (TEM) and
      scanning (SEM) electron microscopy. The results showed a dose-dependent toxicity
      of mancozeb on mouse GCs. Ultrastructural data showed intercellular contact
      alterations, nuclear membrane irregularities, and chromatin marginalization at
      lower concentrations, and showed chromatin condensation, membrane blebbing, and
      cytoplasmic vacuolization at higher concentrations. Morphometric analysis
      evidenced a reduction of mitochondrial length in GCs exposed to mancozeb 0.01-1
      ug/ml and a dose-dependent increase of vacuole dimension. In conclusion, mancozeb
      induced dose-dependent toxicity against GCs in vitro, including ultrastructural
      signs of cell degeneration compatible with apoptosis, likely due to the toxic
      breakdown product ethylenethiourea. These alterations may represent a major cause
      of reduced/delayed/missed oocyte maturation in cases of infertility associated
      with exposure to pesticides.

PMID- 29225324
TI  - Effects of Cilnidipine, an L/N-Type Calcium Channel Blocker, on Carotid
      Atherosclerosis in Japanese Post-Stroke Hypertensive Patients: Results from the
      CA-ATTEND Study.
AB  - AIMS: Although several antihypertensive agents reduced the carotid intima-media
      thickness (IMT), it remains unclear whether those agents affect the
      interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N
      type calcium channel blocker, reduced the common carotid IMT or IAD in post
      stroke hypertensive patients. METHODS: The common carotid IMT and IAD were
      measured at the start of cilnidipine treatment and 12 months from that. The
      changes in the mean max-IMT or IAD between baseline and the 12-month follow-up
      were evaluated and compared between the thick group (max-IMT >=1.1 mm) and the
      normal group (max-IMT <1.1 mm). RESULTS: A total of 603 post-stroke hypertensive
      subjects (mean age=69.3 yr, 378 males) were included in the analysis. At
      baseline, IAD was increased stepwise according to the value of max-IMT (p for
      trend <0.001). Among them, 326 subjects were followed up for 12 months. The mean
      max-IMT from baseline to 12 months did not change in the normal group (-0.01 mm,
      95% confidence interval [CI] -0.03 to 0.01, n=170), whereas a significant
      reduction was observed in the thick group (-0.09 mm, 95% CI -0.13 to -0.05,
      n=156). The mean IAD was significantly reduced during the study period in the
      normal group (-0.14 mm, 95% CI -0.22 to -0.05) as well as in the thick group (
      0.12 mm, 95% CI -0.21 to -0.03). CONCLUSIONS: Cilnidipine promoted the regression
      of common carotid IMT in post-stroke hypertensive patients, especially in the
      thick group. Cilnidipine also reduced the IAD in both normal and thick groups.

PMID- 29225325
TI  - Omentin-1 is Associated with Carotid Plaque Instability among Ischemic Stroke
      Patients.
AB  - AIMS: Omentin-1 was proved to be associated with ischemic stroke clinical
      functional outcome. It also predicted carotid atherosclerosis among metabolic
      syndrome subjects and type 2 diabetes patients. Our aim was to examine the
      association of omentin-1 levels with carotid plaque instability and stenosis
      degree among ischemic stroke patients. METHODS: A total of 173 acute ischemic
      stroke patients were included in this study. Serum omentin-1 levels were assayed.
      Carotid ultrasound examinations were performed to evaluate the carotid plaque
      instability and stenosis degree. Multivariable logistic analyses were used to
      examine the association of serum omentin-1 levels with carotid plaque instability
      and stenosis degree. RESULTS: Ischemic stroke patients with unstable carotid
      plaque had significantly lower levels of serum omentin-1 than patients with
      stable plaque (53 [40.2-64.1] vs 61.8 [52.4-77.2] ng/ml, P<0.01). Subjects in the
      highest tertile of serum omentin-1 levels had a 0.31-fold risk of having unstable
      plaque compared with those in the lowest tertile (P<0.05), and its trend test was
      significant (P for trend=0.03). The integrated discrimination improvement was
      significantly improved in predicting carotid plaque instability when omentin-1
      data was added to the multivariable logistic regression model. No significant
      association was detected between omentin-1 and moderate-severe carotid stenosis
      or occlusion. CONCLUSIONS: Among ischemic stroke patients, higher omentin-1
      levels were inversely associated with carotid plaque instability, but not
      associated with moderate-severe carotid stenosis or occlusion. Omentin-1 may
      represent a biomarker for predicting carotid plaque instability of acute ischemic
      stroke patients.

PMID- 29225327
TI  - Plasma fibrin clot structure and thromboembolism: clinical implications.
AB  - Fibrin formed as a result of fibrinogen polymerization is the main protein
      component of a clot in a test tube and intravascular thrombi in vivo. Fibrin clot
      structure characterized by fiber diameter and pore size differs between healthy
      persons and those with thromboembolic diseases, in part due to the quality and
      quantity of fibrinogen and the magnitude of thrombin generation. A key measure of
      plasma clot structure is its permeability, reflected by the Darcy constant (Ks).
      Reduced Ks is a typical feature of the prothrombotic fibrin clot phenotype, which
      is associated with faster formation of denser fibrin mesh, relatively resistant
      to lysis. Low Ks has been reported in patients with prior or acute myocardial
      infarction (MI), stroke, or venous thromboembolism (encompassing deep vein
      thrombosis [DVT] and pulmonary embolism [PE]), as well as in those with
      prothrombotic conditions (eg, in several thrombophilic states) and in the
      presence of cardiovascular risk factors (eg, obesity). Antithrombotic and
      anticoagulant agents, along with statins, have been shown to increase Ks. Growing
      evidence indicates associations between the properties of plasma fibrin clots and
      morphology of intravascular thrombi in patients with MI. Recently, reduced Ks has
      been shown to predict recurrent thromboembolic episodes in patients with a
      history of stroke, PE, DVT, and their serious complications, including
      postthrombotic syndrome and thromboembolic pulmonary hypertension. We discuss the
      current evidence for the significance of clot density measured in vitro as a
      prognostic marker in a number of clinical conditions associated with elevated
      thromboembolic risk.

PMID- 29225326
TI  - Noninvasive Coronary Plaque Imaging.
AB  - Early identification of high-risk or vulnerable atherosclerotic plaques prone to
      rupture and performing preemptive therapy prior to catastrophic cardiovascular
      events are optimal goals of plaque imaging. Despite the advances in imaging
      modalities to identify vulnerable characteristics, the predictive value of the
      imaging techniques in the clinical setting is still developing. In this regard,
      reliable and high-sensitive imaging modalities identifying vulnerable plaque
      characters that may lead to future cardiovascular events will be useful. In this
      review article, we describe a current non-invasive plaque imaging technique to
      identify high-risk coronary plaque features.

PMID- 29225328
TI  - Gallbladder Hypoplasia, a Congenital Abnormality of the Gallbladder: A Case
      Report.
AB  - BACKGROUND There are different variations in the anatomy of the gallbladder.
      Congenital abnormalities of the gallbladder such as agenesis and hypoplasia are
      rare conditions and difficult to diagnose with imaging studies. Patients are
      usually asymptomatic or have symptoms that mimic gallstone disease. The diagnosis
      is often made intraoperatively and is established by histopathological
      examination. CASE REPORT We report a case of a 62-year-old male who had
      cholelithiasis symptoms and was falsely diagnosed with gallstone disease by
      abdominal ultrasound scan. The patient underwent an operation which revealed a
      rudimentary gallbladder. The histology result showed hypoplastic gallbladder
      tissue. CONCLUSIONS This case suggests that surgeons need to take into
      consideration congenital anomalies of the gallbladder intraoperatively in order
      to avoid any iatrogenic injury to biliary tract during a routine laparoscopic
      cholecystectomy. Intraoperative cholangiography can be a useful tool to avoid
      unnecessary surgical risky interventions.

PMID- 29225329
TI  - Medial Patellofemoral Ligament Reconstruction with Semi-Patellar Tunnel Fixation:
      Surgical Technique and Mid-Term Follow-Up.
AB  - BACKGROUND The present study aimed to describe a new safe and economical
      technique for medial patellofemoral ligament (MPFL) reconstruction with
      satisfactory clinical outcomes, and present the results of a four-year follow-up.
      MATERIAL AND METHODS Thirty-two patients with recurrent patella dislocation, who
      underwent MPFL reconstruction with two semi-patellar tunnels and hardware-free
      patellar fixation between 2011 and 2013, were included in the study. Patella
      stability was tested by an apprehension test preoperatively and at follow-up.
      Knee function was evaluated using the Kujala score, Lysholm score, and Crosby
      Insall grading system. Patellar congruence angle and patellar tilt angle were
      measured using an axial computed tomography scan. Furthermore, objective feelings
      of patients and complications were recorded. RESULTS Thirty knees (30 patients)
      were followed for a minimum of 48 months. The apprehension test was positive in
      all patients preoperatively, but negative at follow-up. Kujala and Lysholm scores
      increased from 58.9+/-9.6 to 92.0+/-4.8 (p<0.001) and 53.3+/-5.6 to 91.6+/-3.5
      (p<0.001), respectively, at the last follow-up. Seventeen patients were graded as
      excellent and 13 were graded as good by the Crosby-Insall grading system. The
      patellar congruence angle and patellar tilt angle also improved significantly. No
      patient experienced patellar re-dislocation, subluxation, or patella fracture.
      Most patients (93%) were satisfied with the surgery. CONCLUSIONS MPFL
      reconstruction with two semi-patellar tunnels and hardware-free patellar fixation
      was described and the study observations indicated it was a safe and economical
      surgical procedure for recurrent patella dislocation with satisfactory results.
      It could be an alternative surgery method for patients with patella recurrent
      dislocation.

PMID- 29225330
TI  - Huntingtin gene repeat size variations affect risk of lifetime depression.
AB  - Huntington disease (HD) is a severe neuropsychiatric disorder caused by a
      cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is
      frequently complicated by depression, it is still unknown to what extent common
      HTT CAG repeat size variations in the normal range could affect depression risk
      in the general population. Using binary logistic regression, we assessed the
      association between HTT CAG repeat size and depression risk in two well
      characterized Dutch cohorts?the Netherlands Study of Depression and Anxiety and
      the Netherlands Study of Depression in Older Persons?including 2165 depressed and
      1058 non-depressed persons. In both cohorts, separately as well as combined,
      there was a significant non-linear association between the risk of lifetime
      depression and HTT CAG repeat size in which both relatively short and relatively
      large alleles were associated with an increased risk of depression (beta = -0.292
      and beta = 0.006 for the linear and the quadratic term, respectively; both P <
      0.01 after adjustment for the effects of sex, age, and education level). The odds
      of lifetime depression were lowest in persons with a HTT CAG repeat size of 21
      (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average
      odds in the total cohort. In conclusion, lifetime depression risk was higher with
      both relatively short and relatively large HTT CAG repeat sizes in the normal
      range. Our study provides important proof-of-principle that repeat polymorphisms
      can act as hitherto unappreciated but complex genetic modifiers of depression.

PMID- 29225331
TI  - Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine
      treated schizophrenia patients.
AB  - Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has
      been reported in schizophrenia, primarily in post-mortem brain tissue. In this
      study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I(Ig2),
      type II, type III, type IV, EGFalpha, EGFbeta, pan-NRG1) in whole blood, and NRG1
      beta1 protein in serum of clozapine-treated schizophrenia patients (N = 71) and
      healthy controls (N = 57). In addition, using cultured peripheral blood
      mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of
      clozapine on NRG1 mRNA isoform and protein expression. We found elevated levels
      of NRG1 mRNA, specifically the EGFalpha (P = 0.0175), EGFbeta (P = 0.002) and
      type I(Ig2) (P = 0.023) containing transcripts, but lower NRG1-beta1 serum
      protein levels (P = 0.019) in schizophrenia patients compared to healthy
      controls. However, adjusting for smoking status attenuated the difference in NRG1
      beta1 serum levels (P = 0.050). Examination of clinical factors showed NRG1
      EGFalpha (P = 0.02) and EGFbeta (P = 0.02) isoform expression was negatively
      correlated with age of onset. However, we found limited evidence that NRG1 mRNA
      isoform or protein expression was associated with current chlorpromazine
      equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC
      clozapine exposure experiment. Our SNP analysis found no robust expression
      quantitative trait loci. Our results represent the first comprehensive
      investigation of NRG1 isoforms and protein expression in the blood of clozapine
      treated schizophrenia patients and suggest levels of some NRG1 transcripts are
      upregulated in those with schizophrenia.

PMID- 29225333
TI  - Technique: A miniature living recording device.

PMID- 29225332
TI  - Effects of acute systemic inflammation on the interplay between sad mood and
      affective cognition.
AB  - Experimental endotoxemia is a translational model to study inflammatory
      mechanisms involved in the pathophysiology of mood disorders including
      depression. Disturbed affective cognition constitutes a core aspect in
      depression, but has never been studied in the context of inflammation. We
      combined experimental endotoxemia with an established experimental mood induction
      procedure to assess the interaction between acute inflammation and sad mood and
      their effects on affective cognition. In this randomized cross-over study, N = 15
      healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study
      day and placebo an otherwise identical study day. The affective Go/Nogo task was
      conducted after experimental induction of neutral and sad mood. Inflammatory
      markers were assessed hourly. Endotoxin application induced a transient systemic
      inflammation, characterized by increased leukocyte counts, TNF-alpha and
      interleukin-6 plasma concentrations (all p < 0.01, interaction effects). Mood
      induction led to greater sadness ratings, with highest ratings when sad mood was
      induced during inflammation (p < 0.05, interaction effect). Based on a 2
      (endotoxin vs. placebo) * 2 (sad vs. neutral mood) * 2 (sad vs. happy Go/Nogo
      target words) factorial design, we observed a significant target * endotoxin
      condition interaction (p < 0.01) reflecting slower responses to sad targets
      during endotoxemia. Additionally, we found a valence * mood interaction (p <
      0.05), reflecting slower reaction times to sad targets in sad mood. In summary,
      acute inflammation and sad mood are risk factors for disturbed affective
      cognition. The results may reflect a mood-congruency effect, with prolonged and
      sustained processing of mood-congruent information during acute inflammation,
      which may contribute to depression risk.

PMID- 29225334
TI  - A change of view: homologous recombination at single-molecule resolution.
AB  - Genetic recombination occurs in all organisms and is vital for genome stability.
      Indeed, in humans, aberrant recombination can lead to diseases such as cancer.
      Our understanding of homologous recombination is built upon more than a century
      of scientific inquiry, but achieving a more complete picture using ensemble
      biochemical and genetic approaches is hampered by population heterogeneity and
      transient recombination intermediates. Recent advances in single-molecule and
      super-resolution microscopy methods help to overcome these limitations and have
      led to new and refined insights into recombination mechanisms, including a
      detailed understanding of DNA helicase function and synaptonemal complex
      structure. The ability to view cellular processes at single-molecule resolution
      promises to transform our understanding of recombination and related processes.

PMID- 29225335
TI  - Genetic architecture: the shape of the genetic contribution to human traits and
      disease.
AB  - Genetic architecture describes the characteristics of genetic variation that are
      responsible for heritable phenotypic variability. It depends on the number of
      genetic variants affecting a trait, their frequencies in the population, the
      magnitude of their effects and their interactions with each other and the
      environment. Defining the genetic architecture of a complex trait or disease is
      central to the scientific and clinical goals of human genetics, which are to
      understand disease aetiology and aid in disease screening, diagnosis, prognosis
      and therapy. Recent technological advances have enabled genome-wide association
      studies and emerging next-generation sequencing studies to begin to decipher the
      nature of the heritable contribution to traits and disease. Here, we describe the
      types of genetic architecture that have been observed, how architecture can be
      measured and why an improved understanding of genetic architecture is central to
      future advances in the field.

PMID- 29225337
TI  - Divergent effects of acute and repeated quetiapine treatment on dopamine neuron
      activity in normal vs. chronic mild stress induced hypodopaminergic states.
AB  - Clinical evidence supports the use of second-generation dopamine D2 receptor
      antagonists (D2RAs) as adjunctive therapy or in some cases monotherapy in
      patients with depression. However, the mechanism for the clinical antidepressant
      effect of D2RAs remains unclear. Specifically, given accumulating evidence for
      decreased ventral tegmental area (VTA) dopamine system function in depression, an
      antidepressant effect of a medication that is expected to further reduce dopamine
      system activity seems paradoxical. In the present paper we used
      electrophysiological single unit recordings of identified VTA dopamine neurons to
      characterize the impact of acute and repeated administration of the D2RA
      quetiapine at antidepressant doses in non-stressed rats and those exposed to the
      chronic mild stress (CMS) rodent depression model, the latter modeling the
      hypodopaminergic state observed in patients with depression. We found that acute
      quetiapine increased dopamine neuron population activity in non-stressed rats,
      but not in CMS-exposed rats. Conversely, repeated quetiapine increased VTA
      dopamine neuron population activity to normal levels in CMS-exposed rats, but had
      no persisting effects in non-stressed rats. These data suggest that D2RAs may
      exert their antidepressant actions via differential effects on the dopamine
      system in a normal vs. hypoactive state. This explanation is supported by prior
      studies showing that D2RAs differentially impact the dopamine system in animal
      models of schizophrenia and normal rats; the present results extend this
      phenomenon to an animal model of depression. These data highlight the importance
      of studying medications in the context of animal models of psychiatric disorders
      as well as normal conditions.

PMID- 29225336
TI  - Psychiatric polygenic risk associates with cortical morphology and functional
      organization in aging.
AB  - Common brain abnormalities in cortical morphology and functional organization are
      observed in psychiatric disorders and aging, reflecting shared genetic
      influences. This preliminary study aimed to examine the contribution of a
      polygenetic risk for psychiatric disorders (PRScross) to aging brain and to
      identify molecular mechanisms through the use of multimodal brain images,
      genotypes, and transcriptome data. We showed age-related cortical thinning in
      bilateral inferior frontal cortex (IFC) and superior temporal gyrus and
      alterations in the functional connectivity between bilateral IFC and between
      right IFC and right inferior parietal lobe as a function of PRScross.
      Interestingly, the genes in PRScross, that contributed most to aging
      neurodegeneration, were expressed in the functioanlly connected cortical regions.
      Especially, genes identified through the genotype-functional connectivity
      association analysis were commonly expressed in both cortical regions and formed
      strong gene networks with biological processes related to neural plasticity and
      synaptogenesis, regulated by glutamatergic and GABAergic transmission,
      neurotrophin signaling, and metabolism. This study suggested integrating genotype
      and transcriptome with neuroimage data sheds new light on the mechanisms of aging
      brain.

PMID- 29225338
TI  - Early-life adversity and cortisol response to social stress: a meta-analysis.
AB  - Early-life adversity has been associated with a life-long increased risk for
      psychopathology and chronic health problems. These long-term negative effects
      have been explained through stress sensitization, which may involve dysregulation
      of the hypothalamic-pituitary-adrenal (HPA) axis through either increased or
      decreased reactivity. The present meta-analysis assessed for the first time the
      effect of early-life adversity on cortisol response to social stress. Thirty data
      sets were included in the meta-analysis, in which early-life adversity and
      salivary cortisol response to social stress were assessed in 4292 individuals of
      different ages. Results indicated a moderate effect size (g = -0.39) in overall
      cortisol levels across studies. Separate analyses of cortisol at different stages
      of response showed large effect sizes at peak and recovery, and a moderate effect
      at baseline. Heterogeneity was large in this sample of studies and several
      moderators were identified. The effect size was larger in studies that focused on
      maltreatment compared to those that included other adversities, and in adults
      compared to children and adolescents. Percent of women in each sample and
      methodological quality were positive predictors of the effect size. Publication
      bias may be present, but the analysis was hampered by the high heterogeneity.
      Therefore, these results support the association between early-life adversity and
      blunted cortisol response to social stress, and they suggest that the long-term
      negative effects of early-life adversity may reach maximum levels in adults.

PMID- 29225339
TI  - Early speech development in Koolen de Vries syndrome limited by oral praxis and
      hypotonia.
AB  - Communication disorder is common in Koolen de Vries syndrome (KdVS), yet its
      specific symptomatology has not been examined, limiting prognostic counselling
      and application of targeted therapies. Here we examine the communication
      phenotype associated with KdVS. Twenty-nine participants (12 males, 4 with KANSL1
      variants, 25 with 17q21.31 microdeletion), aged 1.0-27.0 years were assessed for
      oral-motor, speech, language, literacy, and social functioning. Early history
      included hypotonia and feeding difficulties. Speech and language development was
      delayed and atypical from onset of first words (2; 5-3; 5 years of age on
      average). Speech was characterised by apraxia (100%) and dysarthria (93%), with
      stuttering in some (17%). Speech therapy and multi-modal communication (e.g.,
      sign-language) was critical in preschool. Receptive and expressive language
      abilities were typically commensurate (79%), both being severely affected
      relative to peers. Children were sociable with a desire to communicate, although
      some (36%) had pragmatic impairments in domains, where higher-level language was
      required. A common phenotype was identified, including an overriding 'double hit'
      of oral hypotonia and apraxia in infancy and preschool, associated with severely
      delayed speech development. Remarkably however, speech prognosis was positive;
      apraxia resolved, and although dysarthria persisted, children were intelligible
      by mid-to-late childhood. In contrast, language and literacy deficits persisted,
      and pragmatic deficits were apparent. Children with KdVS require early,
      intensive, speech motor and language therapy, with targeted literacy and social
      language interventions as developmentally appropriate. Greater understanding of
      the linguistic phenotype may help unravel the relevance of KANSL1 to child speech
      and language development.

PMID- 29225341
TI  - Humoral immunity, the underestimated player in hepatitis B.

PMID- 29225340
TI  - Genetic and experimental evidence for the involvement of the CD6 lymphocyte
      receptor in psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease with a strong genetic background
      and is triggered by environmental factors. Available evidence supports CD6, a
      lymphocyte surface receptor mostly expressed by T cells, as a putative target in
      autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the
      treatment of certain autoimmune disorders, including psoriasis. Here, we present
      novel evidence in mice and humans for a direct involvement of CD6 in psoriasis
      pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like
      skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower
      epidermal thickness and local reduced production of pro-inflammatory cytokines,
      namely, interleukin-17A. Thus, isolated CD4+CD62L+ T cells from CD6-deficient
      mice displayed decreased in vitro T-helper type 17 polarization. Second, a
      statistically significant association between CD6 single-nucleotide polymorphisms
      (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was
      demonstrated in a cohort of 304 patients at three public hospitals from the
      metropolitan area of Barcelona. Taken together, these results provide new
      supportive evidence of the contribution of the CD6 lymphocyte receptor in
      psoriasis at both experimental and clinical levels.Cellular and Molecular
      Immunology advance online publication, 11 December 2017;
      doi:10.1038/cmi.2017.119.

PMID- 29225344
TI  - Thrombosis: Reducing thrombosis in CKD.

PMID- 29225342
TI  - Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA
      sequencing.
AB  - Characterising the hierarchy of mammary epithelial cells (MECs) and how they are
      regulated during adult development is important for understanding how breast
      cancer arises. Here we report the use of single-cell RNA sequencing to determine
      the gene expression profile of MECs across four developmental stages;
      nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184
      cells identifies 15 clusters, few of which could be fully characterised by a
      single marker gene. We argue instead that the epithelial cells-especially in the
      luminal compartment-should rather be conceptualised as being part of a continuous
      spectrum of differentiation. Furthermore, our data support the existence of a
      common luminal progenitor cell giving rise to intermediate, restricted alveolar
      and hormone-sensing progenitors. This luminal progenitor compartment undergoes
      transcriptional changes in response to a full pregnancy, lactation and
      involution. In summary, our results provide a global, unbiased view of adult
      mammary gland development.

PMID- 29225343
TI  - Advances in the understanding and treatment of sepsis-induced immunosuppression.
AB  - Sepsis is defined as a life-threatening organ dysfunction that is caused by a
      dysregulated host response to infection. Sepsis can induce acute kidney injury
      and multiple organ failures and represents the most common cause of death in the
      intensive care unit. Sepsis initiates a complex immune response that varies over
      time, with the concomitant occurrence of both pro-inflammatory and anti
      inflammatory mechanisms. As a result, most patients with sepsis rapidly display
      signs of profound immunosuppression, which is associated with deleterious
      consequences. Scientific advances have highlighted the role of metabolic failure,
      epigenetic reprogramming, myeloid-derived suppressor cells, immature suppressive
      neutrophils and immune alterations in primary lymphoid organs (the thymus and
      bone marrow) in sepsis. An improved understanding of the mechanisms underlying
      this immunosuppression as well as of the similarities between sepsis-induced
      immunosuppression and immune defects in cancer or immunosenescence has led to
      novel therapeutic strategies aimed at stimulating immune function in patients
      with sepsis. Trials assessing the therapeutic benefit of IL-7, granulocyte
      macrophage colony-stimulating factor (GM-CSF) and antibodies against programmed
      cell death protein 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) for the
      treatment of sepsis are in progress. The reappraisal of sepsis pathophysiology
      has also resulted in a novel approach to the design of clinical trials evaluating
      sepsis treatments, based on an evaluation of the immune status and biomarker
      based stratification of patients.

PMID- 29225346
TI  - Actin polymerization is reduced in the anterior cingulate cortex of elderly
      patients with schizophrenia.
AB  - Recent reports suggest abnormalities in the regulation of actin cytoskeletal
      dynamics in schizophrenia, despite consistent evidence for normal actin
      expression. We hypothesized that this may be explained by changes in the
      polymerization state of actin, rather than in total actin expression. To test
      this, we prepared filamentous actin (F-actin, polymeric) and globular actin (G
      actin, monomeric) fractions from postmortem anterior cingulate cortex from 16
      patients with schizophrenia and 14 comparison subjects. Additionally, binding of
      fluorescently-labeled phalloidin, a selectively F-actin-binding peptide, was
      measured in unfractionated samples from the same subjects. Western blot analysis
      of fractions revealed decreased F-actin, increased G-actin, and decreased ratios
      of F-actin/total actin and F-actin/G-actin in schizophrenia. Decreased phalloidin
      binding to F-actin in parallel experiments in the same subjects independently
      supports these findings. These results suggest a novel aspect of schizophrenia
      pathophysiology and are consistent with previous evidence of reduced dendritic
      spine density and altered synaptic plasticity in schizophrenia, both of which
      have been linked to cytoskeletal abnormalities.

PMID- 29225345
TI  - Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood
      disorders.
AB  - Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood
      disorders. Recent studies suggest that they share certain psychopathological
      features and common risk genes, but unraveling the full genetic architecture
      underlying the risk of major mood disorders remains an important scientific task.
      The public genome-wide association study (GWAS) data sets offer the opportunity
      to examine this topic by utilizing large amounts of combined genetic data, which
      should ultimately allow a better understanding of the onset and development of
      these illnesses. Genome-wide meta-analysis was performed by combining two GWAS
      data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by
      replication analyses for the loci of interest in independent 12,364 cases and
      76,633 controls from additional samples that were not included in the two GWAS
      data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was
      significant in both discovery and replication samples. When combining all
      samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3
      (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant
      association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel
      risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD
      with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide
      significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA
      expression of certain nearby genes in cerebellum. In conclusion, we have
      identified several novel loci associated with major mood disorders, adding
      further support for shared genetic risk between BPD and MDD. Our study highlights
      the necessity and importance of mining public data sets to explore risk genes for
      complex diseases such as mood disorders.

PMID- 29225347
TI  - Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar
      disorder.
AB  - Bipolar disorder (BD) has been previously associated with accelerated aging; yet,
      the mechanisms underlying this association are largely unknown. The epigenetic
      clock has been increasingly recognized as a valuable aging marker, although its
      association with other biological clocks in BD patients and high-risk subjects,
      such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been
      investigated. We included 22 patients with BD I, 16 siblings of BD patients, and
      20 healthy controls in this analysis. DNA was isolated from peripheral blood and
      interrogated for genome-wide DNA methylation, mtDNA copy number, and telomere
      length. DNA methylation age (DNAm age) and accelerated aging were calculated
      using the Horvath age estimation algorithm in blood and in postmortem brain from
      BD patients and nonpsychiatric controls using publicly available data. Older BD
      patients presented significantly accelerated epigenetic aging compared to
      controls, whereas no difference was detected among the younger subjects. Patients
      showed higher levels of mtDNA copy number, while no difference was found between
      controls and siblings. mtDNA significantly correlated with epigenetic age
      acceleration among older subjects, as well and with global functioning in our
      sample. Telomere length did not show significant differences between groups, nor
      did it correlate with epigenetic aging or mtDNA copy number. These results
      suggest that BD may involve an accelerated epigenetic aging, which might
      represent a novel target for treating BD and subjects at risk. In particular, our
      results suggest a complex interplay between biological clocks to determine the
      accelerated aging and its consequences in BD.

PMID- 29225349
TI  - Tau haplotypes support the Asian ancestry of the Roma population settled in the
      Basque Country.
AB  - We examined tau haplotype frequencies in two different ethnical groups from the
      Basque Country (BC): Roma people and residents of European ancestry (general
      population). In addition, we analyzed the spatial distribution of tau haplotypes
      in Eurasian populations to explore the genetic affinities of the Romani groups
      living in Europe in a broader scope. The 17q21.31 genomic region was
      characterized through the genotyping of two diagnostic single nucleotide
      polymorphisms, SNPs (rs10514879 and rs199451), which allow the identification of
      H1 and H2 haplotypes. A significant heterozygous deficit was detected in the
      Romani for rs10514879. The H2 haplotype frequency proved to be more than twice in
      the BC general population (0.283) than in the Roma people (0.127). In contrast,
      H2 frequency proved to be very similar between Basque and Hungarian Romani, and
      similar to the H2 frequencies found in northwestern India and Pakistan as well.
      Several statistical analyses unveiled genetic structuring for the MAPT diversity,
      mirrored in a significant association between geography and genetic distances,
      with an upward trend of H2 haplotype frequencies from Asia to Europe. Yet, Roma
      samples did not fit into this general spatial patterning because of their
      discrepancy between geographical position and H2 frequency. Despite the long
      spatial coexistence in the Basque region between the residents of European
      ancestry and the Roma, the latter have preserved their Asian genetic ancestry.
      Bearing in mind the lack of geographical barriers between both ethnical groups,
      these findings support the notion that sociocultural mores might promote
      assortative matings in human populations.

PMID- 29225348
TI  - A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals
      susceptibility loci in humans.
AB  - The etiology of individual differences in human anxiousness is complex and
      includes contributions from genetic, epigenetic (i.e., DNA methylation) and
      environmental factors. Past genomic approaches have been limited in their ability
      to detect human anxiety-related differences in these factors. To overcome these
      limitations, we employed both a multi-dimensional characterization method, to
      select monozygotic twin pairs discordant for anxiety, and whole genome DNA
      methylation sequencing. This approach revealed 230 anxiety-related differentially
      methylated loci that were annotated to 183 genes, including several known stress
      related genes such as NAV1, IGF2, GNAS, and CRTC1. As an initial validation of
      these findings, we tested the significance of an overlap of these data with
      anxiety-related differentially methylated loci that we previously reported from a
      key neural circuit of anxiety (i.e., the central nucleus of the amygdala) in
      young monkeys and found a significant overlap (P-value < 0.05) of anxiety-related
      differentially methylated genes, including GNAS, SYN3, and JAG2. Finally,
      sequence motif predictions of all the human differentially methylated regions
      indicated an enrichment of five transcription factor binding motifs, suggesting
      that DNA methylation may regulate gene expression by mediating transcription
      factor binding of these transcripts. Together, these data demonstrate
      environmentally sensitive factors that may underlie the development of human
      anxiety.

PMID- 29225350
TI  - Maternal-by-environment but not genotype-by-environment interactions in a fish
      without parental care.
AB  - The impact of environmental conditions on the expression of genetic variance and
      on maternal effects variance remains an important question in evolutionary
      quantitative genetics. We investigate here the effects of early environment on
      variation in seven adult life history, morphological, and secondary sexual traits
      (including sperm characteristics) in a viviparous poeciliid fish, the
      mosquitofish Gambusia holbrooki. Specifically, we manipulated food availability
      during early development and then assessed additive genetic and maternal effects
      contributions to the overall phenotypic variance in adults. We found higher
      heritability for female than male traits, but maternal effects variance for
      traits in both sexes. An interaction between maternal effects variance and
      rearing environment affected two adult traits (female age at maturity and male
      size at maturity), but there was no evidence of trade-offs in maternal effects
      across environments. Our results illustrate (i) the potential for pre-natal
      maternal effects to interact with offspring environment during development,
      potentially affecting traits through to adulthood and (ii) that genotype-by
      environment interactions might be overestimated if maternal-by-environment
      interactions are not accounted for, similar to heritability being overestimated
      if maternal effects are ignored. We also discuss the potential for dominance
      genetic variance to contribute to the estimate of maternal effects variance.

PMID- 29225351
TI  - Metabolome-wide association studies for agronomic traits of rice.
AB  - Identification of trait-associated metabolites will advance the knowledge and
      understanding of the biosynthetic and catabolic pathways that are relevant to the
      complex traits of interest. In the past, the association between metabolites
      (treated as quantitative traits) and genetic variants (e.g., SNPs) has been
      extensively studied using metabolomic quantitative trait locus (mQTL) mapping.
      Nevertheless, the research on the association between metabolites with agronomic
      traits has been inadequate. In practice, the regular approaches for QTL mapping
      analysis may be adopted for metabolites-phenotypes association analysis due to
      the similarity in data structure of these two types of researches. In the study,
      we compared four regular QTL mapping approaches, i.e., simple linear regression
      (LR), linear mixed model (LMM), Bayesian analysis with spike-slab priors (Bayes
      B) and least absolute shrinkage and selection operator (LASSO), by testing their
      performances on the analysis of metabolome-phenotype associations. Simulation
      studies showed that LASSO had the higher power and lower false positive rate than
      the other three methods. We investigated the associations of 839 metobolites with
      five agronomic traits in a collection of 533 rice varieties. The results implied
      that a total of 25 metabolites were significantly associated with five agronomic
      traits. Literature search and bioinformatics analysis indicated that the
      identified 25 metabolites are significantly involved in some growth and
      development processes potentially related to agronomic traits. We also explored
      the predictability of agronomic traits based on the 839 metabolites through cross
      validation, which showed that metabolomic prediction was efficient and its
      application in plant breeding has been justified.

PMID- 29225352
TI  - Response to Janecka et al. 2017.

PMID- 29225353
TI  - Urban landscape genomics identifies fine-scale gene flow patterns in an avian
      invasive.
AB  - Invasive species exert a serious impact on native fauna and flora and have been
      the target of many eradication and management efforts worldwide. However, a lack
      of data on population structure and history, exacerbated by the recency of many
      species introductions, limits the efficiency with which such species can be kept
      at bay. In this study we generated a novel genome of high assembly quality and
      genotyped 4735 genome-wide single nucleotide polymorphic (SNP) markers from 78
      individuals of an invasive population of the Javan Myna Acridotheres javanicus
      across the island of Singapore. We inferred limited population subdivision at a
      micro-geographic level, a genetic patch size (~13-14 km) indicative of a
      pronounced dispersal ability, and barely an increase in effective population size
      since introduction despite an increase of four to five orders of magnitude in
      actual population size, suggesting that low population-genetic diversity
      following a bottleneck has not impeded establishment success. Landscape genomic
      analyses identified urban features, such as low-rise neighborhoods, that
      constitute pronounced barriers to gene flow. Based on our data, we consider an
      approach targeting the complete eradication of Javan Mynas across Singapore to be
      unfeasible. Instead, a mixed approach of localized mitigation measures taking
      into account urban geographic features and planning policy may be the most
      promising avenue to reducing the adverse impacts of this urban pest. Our study
      demonstrates how genomic methods can directly inform the management and control
      of invasive species, even in geographically limited datasets with high gene flow
      rates.

PMID- 29225354
TI  - History-driven population structure and asymmetric gene flow in a recovering
      large carnivore at the rear-edge of its European range.
AB  - Understanding the mechanisms and patterns involved in population recoveries is
      challenging and important in shaping conservation strategies. We used a
      recovering rear-edge population of brown bears at their southernmost European
      range in Greece as a case study (2007-2010) to explore the recovery genetics at a
      species' distribution edge. We used 17 microsatellite and a mitochondrial markers
      to evaluate genetic structure, estimate effective population size and genetic
      diversity, and infer gene flow between the identified subpopulations. To
      understand the larger picture, we also compared the observed genetic diversity of
      each subpopulation with other brown bear populations in the region. The results
      indicate that the levels of genetic diversity for bears in western Greece are the
      lowest recorded in southeastern Europe, but still higher than those of other
      genetically depauperate bear populations. Apart from a complete separation of
      bear populations in eastern and western Greece, our results also indicate a
      considerable genetic sub-structuring in the West. As bear populations in Greece
      are now recovering, this structure is dissolving through a "recovery cascade" of
      asymmetric gene flow from South to North between neighboring subpopulations,
      mediated mainly by males. Our study outlines the importance of small, persisting
      populations, which can act as "stepping stones" that enable a rapid population
      expansion and recovery. This in turn makes their importance much greater than
      their numeric or genetic contribution to a species as a whole.

PMID- 29225357
TI  - Marine microbiology: Illuminating the importance of nitrite oxidation.

PMID- 29225356
TI  - Quantitative neurobiological evidence for accelerated brain aging in alcohol
      dependence.
AB  - The premature aging hypothesis of alcohol dependence proposes that the
      neurobiological and behavioural deficits in individuals with alcohol dependence
      are analogous to those of chronological aging. However, to date no systematic
      neurobiological evidence for this hypothesis has been provided. To test the
      hypothesis, 119 alcohol-dependent subjects and 97 age- and gender-matched healthy
      control subjects underwent structural MRI. Whole-brain grey matter volume maps
      were computed from structural MRI scans using voxel-based morphometry and
      parcelled into a comprehensive set of anatomical brain regions. Regional grey
      matter volume averages served as the basis for cross-regional similarity analyses
      and a brain age model. We found a striking correspondence between regional
      patterns of alcohol- and age-related grey matter loss across 110 brain regions.
      The brain age model revealed that the brain age of age-matched AD subjects was
      increased by up to 11.7 years. Interestingly, while no brain aging was detected
      in the youngest AD subjects (20-30 years), we found that alcohol-related brain
      aging systematically increased in the following age decades controlling for
      lifetime alcohol consumption and general health status. Together, these results
      provide strong evidence for an accelerated aging model of AD and indicate an
      elevated risk of alcohol-related brain aging in elderly individuals.

PMID- 29225355
TI  - Evolutionary conservation and functional divergence of the LFK gene family play
      important roles in the photoperiodic flowering pathway of land plants.
AB  - ZEITLUPE (ZTL), LOV KELCH PROTEIN 2 (LKP2), and FLAVIN-BINDING KELCH REPEAT F-BOX
      1 (FKF1)-blue-light photoreceptors-play important roles in regulating the
      circadian clock and photoperiodic flowering pathway in plants. In this study,
      phylogenetic analysis revealed that the LOV (Light, Oxygen, or Voltage) and Kelch
      repeat-containing F-box (LFK) gene family can be classified into two clades,
      ZTL/LKP2 and FKF1, with clear differentiation between monocots and dicots within
      each clade. The LFK family genes underwent strong purifying selection; however,
      signatures of positive selection to adapt to local conditions still existed in 18
      specific codons. In 87 diverse maize inbred lines, significant differences were
      identified (P <= 0.01) for days to female flowering between the haplotypes
      consisting of eight positive selection sites at ZmFKF1b corresponding to tropical
      and temperate maize groups of the phylogenetic tree, indicating a key role of
      ZmFKF1b in maize adaptive evolution. In addition, positive coevolution was
      detected in the domains of the LFK family for long-term cooperation to targets.
      The Type-I and Type-II functional divergence analysis revealed
      subfunctionalization or neofunctionalization of the LFKs, and the ZTL subfamily
      is most likely to maintain the ancestral function of LFKs. Over 50% of critical
      amino acid sites involved in the functional divergence were identified in the
      Kelch repeat domain, resulting in the distinction of substrates for
      ubiquitination and degradation. These results suggest that evolutionary
      conservation contributes to the maintenance of critical physiological functions,
      whereas functional divergence after duplication helps to generate diverse
      molecular regulation mechanisms.

PMID- 29225358
TI  - Effect of Margin Designs on the Marginal Adaptation of Zirconia Copings.
AB  - Objective: The aim of this in vitro study was to investigate the effect of
      Shoulder versus Chamfer margin design on the marginal adaptation of zirconia (Zr)
      copings. Materials and Methods: 40 extracted molar teeth were mounted in resin
      and prepared for zirconia crowns with two margin preparation designs (20=Shoulder
      and 20=Chamfer). The copings were manufactured by Cercon(r) (DeguDent GmbH,
      Germany) using the CAD/CAM system for each tooth. They were tried on each tooth,
      cemented, thermocycled, re-embedded in resin and were subsequently cross
      sectioned centrally into two equal mesial and distal halves. They were examined
      under electron microscope at 200 X magnification and the measurements were
      recorded at 5 predetermined points in micrometers (um). Results: The overall mean
      marginal gap for the two groups was found to be 206.98+42.78um with Shoulder
      margin design (Marginal Gap=199.50+40.72um) having better adaptation compared to
      Chamfer (Marginal Gap=214.46+44.85um). The independent-samples t-test showed a
      statistically non-significant difference (p=.113) between the means of marginal
      gap for Shoulder and Chamfer margin designs and the measurements were recorded at
      5 predetermined points for the two groups. Conclusions: The Chamfer margin design
      appeared to offer the same adaptation results as the Shoulder margin design.

PMID- 29225359
TI  - Psychometric Properties of the Croatian Language Version of the Dental
      Environment Stress Questionnaire on Dental Medicine Students.
AB  - Objective: To develop the Croatian version of the 41-item Dental Environment
      Stress questionnaire (DES) for stress assessment of dental students in both,
      preclinical and clinical years of study and to test its psychometric properties
      in Croatian dental student population. Materials and Methods: The English version
      of the 41-Item DES questionnaire was first translated into the Croatian language.
      Subsequently, it was set on the google drive and filled out by a total of 202
      students from the School of Dental Medicine, University of Zagreb and 30
      additional students from other Faculties. Students also assessed their overall
      level of stress on the Likert scale (1=no stress, 5=highest level of stress).
      Internal consistency was tested on 202 dental students; test-retest reliability
      on 30 dental students who filled out the same questionnaire twice; convergent
      validity on 202 dental students; and divergent validity on 202 dental students
      and 30 students from faculties not belonging to the biomedicine group. Results:
      Internal consistency showed high Cronbach alpha coefficient (0.9) and test-retest
      reliability showed no significant difference (P>0.05) within the period of 14
      days when stress level had not changed (vacation). Convergent validity was
      confirmed by the significant association between the DES summary scores and the
      self- perceived level of stress (Spearman's rho=0.881; P<0.001). Divergent
      validity was confirmed by significantly lower DES summary scores in students not
      belonging to the Biomedicine group (t=7.5, P<0.001). Conclusion: Excellent
      psychometric properties of the Croatian version of the DES questionnaire enable
      its utilization for assessment of stress level in Croatian dental students.

PMID- 29225360
TI  - Facial Anthropometric Norms among Kosovo - Albanian Adults.
AB  - Background: The development of an anthropometric craniofacial database is a
      necessary multidisciplinary proposal. Aim: The aim of this study was to establish
      facial anthropometric norms and to investigate into sexual dimorphism in facial
      variables among Kosovo Albanian adults. Materials and Methods: The sample
      included 204 students of Dental School, Faculty of Medicine, University of
      Pristina. Using direct anthropometry, a series of 8 standard facial measurements
      was taken on each subject with digital caliper with an accuracy of 0.01 mm (Boss,
      Hamburg-Germany). The normative data and percentile rankings were calculated.
      Gender differences in facial variables were analyzed using t- test for
      independent samples (p<0.05). The index of sexual dimorphism (ISD) and percentage
      of sexual dimorphism were calculated for each facial measurement. Results N:
      ormative data for all facial anthropometric measurements in males were higher
      than in females. Male average norms compared with the female average norms
      differed significantly from each other (p>0.05).The highest index of sexual
      dimorphism (ISD) was found for the lower facial height 1.120, for which the
      highest percentage of sexual dimorphism, 12.01%., was also found. The lowest ISD
      was found for intercanthal width, 1.022, accompanied with the lowest percentage
      of sexual dimorphism, 2.23%. Conclusion: The obtained results have established
      the facial anthropometric norms among Kosovo Albanian adults. Sexual dimorphism
      has been confirmed for each facial measurement.

PMID- 29225361
TI  - Comparison of Shaping Ability of 10 Rotary and Reciprocating Systems: an In Vitro
      Study with AutoCad.
AB  - Objective: The aim of this study was to compare the cutting are, root canal
      anatomy preservation and non-instrumented areas of F360(r), F6-SkyTaper(r),
      Hyflex-EDM(r), iRACE(r), Neoniti(r), O.Shape(r), P.Next(r), Reciproc(r), Revo
      S(r) and Wave-One-Gold(r) size 25 files. Materials and Methods: 300 teeth with a
      single straight root and a circular or elliptical root canal were divided into 10
      groups (1-F360(r), 2- F6-SkyTaper(r), 3-Hyflex-EDM(r), 4-iRACE(r), 5-Neoniti(r),
      6-O.Shape(r), 7-P.Next(r), 8-Reciproc(r), 9-Revo-S(r) and 10-Wave-One-Gold(r))
      cut into 3 cross sections using an ultrafine cutting disc. They were photographed
      under a stereo microscope and preinstrumentation analyses were made before
      rebuilding the teeth with# 10 K- File and epoxy glue. A glide path was created
      with #10 and #15 K files and each group was instrumented using rotary or
      reciprocating systems. Cutting areas, root canal anatomy preservation and non
      instrumented areas were analyzed using the AutoCAD 2015 Levene's test, the
      Welch's test, and the Games-Howell's test. The Pearson's chi-squared test was
      used for statistical analysis. Results: Levene's test showed no equality of
      variances (P<0.05), therefore Welch's and Games-Howell's tests were applied to
      cutting areas, showing significant differences in all thirds and overall
      (P<0.05). No differences in root canal anatomy preservation were observed
      (P>0.05). In non-instrumented areas, significant differences were found (P<0.05)
      in middle third being better in Reciproc(r), Neoniti(r) and WaveOneGold(r), and
      in apical thirds being higher P.Next(r), Reciproc(r), HyflexEDM(r), Neoniti(r)
      and WaveOneGold(r). Conclusions: In cutting area, P.Next(r) and Reciproc(r) were
      superior in coronal third, Neoniti(r) and Hyflex EDM(r) medially and apically and
      Neoniti(r) and Reciproc(r) overall. Regarding the root canal anatomy
      preservation, all systems were similar. For non-instrumented areas, all systems
      achieved similar results coronally, but Reciproc(r), Neoniti(r) and Wave One
      Gold(r) were superior in middle third and P.Next(r), Reciproc(r), Hyflex EDM(r),
      Neoniti(r) and Wave One Gold(r) were superior in apically.

PMID- 29225362
TI  - Frequency of bacetrial content finding in persistant periapical lesions.
AB  - Objectives: To determine the percentage of persistant apical lesions positive for
      bacterial nucleic acids, to detect microorganisms difficult to cultivate in
      persistant apical lesions by PCR and relate them to endodontic failure, clinical
      symptoms and diabetes mellitus. Materials and methods: The samples of persistent
      apical lesions were collected during apicoectomy. Bacterial ubiquitous primer 16S
      rRNA was used to detect 16S ribosomal RNA in 36 samples. A species-specific PCR
      was performed with primers targeted to the bacterial 16S rRNA genes of Prevotella
      Nigrescens, Pseudoramibacter alactolyticus, and Propionobacterium propionicum.
      Results: Six samples (16.67%) were positive for bacterial ribosomal RNA.
      Pseudoramibacter alactolyticus was detected in three samples. Propionibacterium
      propionicum and Prevotella nigrescens were detected in one sample each. The
      prevalence of infection of such lesions with P. intermedia, P. propionicum and P.
      alactolyticus is low. Conslusion: The study we conducted gave insufficient data
      about extraradicular infection and its connection with diabetes mellitus and
      clinical symptoms. Conclusions: Apical lesions persisting after endodontic
      treatment could harbor microorganisms other than Actinomyces and Propionicum
      species.

PMID- 29225363
TI  - Forensic Identification of Decomposed Human Body through Comparison between Ante
      Mortem and Post-Mortem CT Images of Frontal Sinuses: Case Report.
AB  - Objective: The aim of this paper is to report on a case of positive human
      identification of a decomposed body after the comparison of ante-mortem (AM) and
      port-mortem (PM) computed tomography images of frontal sinus. Case report: An
      unknown, highly decomposed human body, aged between 30 and 40 years, was found in
      a forest region in Brazil. The dental autopsy revealed several teeth missing AM
      and the presence of removable partial prostheses. The search for AM data resulted
      in a sequence of 20 axial images of the paranasal sinuses obtained by Multislice
      Computed Tomography (MSCT). PM reproduction of the MSCT images was performed in
      order to enable a comparative identification. After a direct confrontation
      between AM/PM MSCT, the data were collected for morphological findings,
      specifically for the lateral expansion of the left lobe, the anteroposterior
      dimension, and the position of median and accessory septa of the sinuses.
      Conclusion: The importance of storing and interpreting radiographic medical data
      properly is highlighted in this text, thus pointing out the importance of
      application of forensic radiology in the field of law.

PMID- 29225364
TI  - A Young Patient with Temporomandibular Joint Osteoarthritis: Case Report.
AB  - This paper describes a case of a young patient who sought help because of pain in
      the right temporomandibular joint (TMJ). She also reported increasing of pain
      during chewing. Clinical examination revealed limited mouth opening with
      uncorrected deviation to the ipsilateral side. Palpation of the lateral pole of
      the right condyle discovered crepitus, and maximum assisted opening elicited a
      report of "familiar pain". The diagnosis of osteoarthritis of the TMJ (RDC / TMD
      criteria, Axis I, Group III) was confirmed by CBCT of TMJ. There is no "gold
      standard" for the management of TMD, but the need for TMD treatment has to be
      based on precise indications related to the presence of pain, limitation in
      function of the lower jaw and signs of degenerative joint disease. Conservative,
      reversible therapeutic procedures are considered as the first choice for TMD
      treatment and their task is to improve the function of the entire masticatory
      system. In this case patient was treated with the combination of physical therapy
      and stabilization splint, in order to reduce the pain and restore the normal
      function of the lower jaw. At 6 months' follow-up symptoms have almost completely
      disappeared, while 3 years later, the patient still has no significant subjective
      symptoms. In the present case non-invasive therapy was sufficient to bring,
      otherwise recurrent nature of osteoarthritis, in complete remission and keep it
      like that for years.

PMID- 29225365
TI  - A Review of the Effectiveness and Side-Effects of Fluocinolone Acetonide 0.1% in
      the Treatment of Oral Mucosal Diseases.
AB  - Topical steroids have been widely used in the treatment of symptomatic oral
      lesions to reduce pain and inflammation. Potent topical steroids such as
      clobetasol propionate, fluocinolone acetonide (FA), and fluocinonide have been
      widely used in the treatment of severe oral mucosal lesions. Many reports have
      demonstrated that these steroids were effective in treating oral lesions with
      only minor side-effects. This review describes the effectiveness and side-effects
      of using FA 0.1% in the treatment of symptomatic oral lichen planus (OLP), oral
      lichenoid drug reaction (OLDR), oral pemphigus, and herpes associated erythema
      multiforme (HAEM). FA 0.1% was effective and safe in the treatment of patients
      with multiple systemic diseases and a pregnant patient with HAEM. Moreover, this
      topical steroid rapidly reduced pain, inflammation, and enhanced lesion healing
      with no serious side-effects other than pseudomembranous candidiasis, which is
      easily treated. In some cases, a long-term treatment with FA 0.1% resulted in
      hyperpigmentation at the areas of previously healed oral lesions; however, this
      hyperpigmentation was gradually resolved after discontinuing topical steroid
      treatment.

PMID- 29225366
TI  - Solvent Dependence of Cyanoindole Fluorescence Lifetime.
AB  - Several cyanotryptophans have been shown to be useful biological fluorophores.
      However, how their fluorescence lifetimes vary with solvent has not been
      examined. In this regard, herein we measure the fluorescence decay kinetics as
      well as the absorption and emission spectra of six cyanoindoles in different
      solvents. In particular, we find, among other results, that only 4-cyanoindole
      affords a long fluorescence lifetime and hence high quantum yield in H2O.
      Therefore, our measurements provide not only a guide for choosing which
      cyanotryptophan to use in practice but also data for computational modeling of
      the substitution effect on the electronic transitions of indole.

PMID- 29225367
TI  - The Impact of Organic Additives on Copper Trench Microstructure.
AB  - Organic additives are typically used in the pulse electrodeposition of copper
      (Cu) to prevent void formation during the filling of high aspect ratio features.
      In this work, the role of bath chemistry as modified by organic additives was
      investigated for its effects on Cu trench microstructure. Polyethylene glycol
      (PEG), bis(3-sulfopropyl) disulfide (SPS), and Janus green b (JGB) concentrations
      were varied in the Cu electrodeposition bath. Results indicated a correlation
      between the JGB/SPS ratio and the surface roughness and residual stresses in the
      Cu. Electron backscattering diffraction (EBSD) and transmission Kikuchi
      diffraction (TKD) were used to study the cross-sectional microstructure in the
      trenches. Finer grain morphologies appeared in trenches filled with organic
      additives as compared to additive-free structures. Cu trench (111) texture also
      decreased with increasing organic additive concentrations due to more pronounced
      influence of sidewall seed layers on trench features. Twin density in the
      microstructure closely tracked calculated stresses in the Cu trenches. A
      comprehensive microstructural analysis was conducted in this study, on an area of
      focus that has garnered little attention from the literature, yet can have a
      major impact on microelectronic reliability.

PMID- 29225368
TI  - Rates, intrinsic linkages, and multistate population dynamics.
AB  - Demographic analyses of multistate populations are commonplace, as are situations
      where population stocks are known but population flows are not. Still,
      demographic models for multistate populations with changing rates remain at an
      early stage of development, limiting dynamic analyses and analytical projections.
      Here, a new approach, the Intrinsic Linkage-Rate Ratio (IL-RR) model, is
      presented and explored. The key IL parameter, w, is a simple weight for
      projecting populations. Using the ultimate state composition implied by the
      prevailing rates, the IL-RR model provides new relationships that connect
      multistate populations over time and allow analytical population projections.
      Parameter w reflects population metabolism and scales the level of the transfer
      rates. Compositional change is driven by the sequence of implicit stable
      population compositions. The IL-RR approach also provides a new method for
      estimating transfer rates within an interval from population numbers at the
      beginning and end of the interval. The new relationships developed advance the
      ability of demographers to model multistate populations with changing rates and
      to relate population stocks and flows.

PMID- 29225369
TI  - Embracing uncertainty in applied ecology.
AB  - Applied ecologists often face uncertainty that hinders effective decision
      making.Common traps that may catch the unwary are: ignoring uncertainty,
      acknowledging uncertainty but ploughing on, focussing on trivial uncertainties,
      believing your models, and unclear objectives.We integrate research insights and
      examples from a wide range of applied ecological fields to illustrate advances
      that are generally underused, but could facilitate ecologists' ability to plan
      and execute research to support management.Recommended approaches to avoid
      uncertainty traps are: embracing models, using decision theory, using models more
      effectively, thinking experimentally, and being realistic about
      uncertainty.Synthesis and applications. Applied ecologists can become more
      effective at informing management by using approaches that explicitly take
      account of uncertainty.

PMID- 29225370
TI  - Macrophyte Community Response to Nitrogen Loading and Thermal Stressors in
      Rapidly Flushed Mesocosm Systems.
AB  - A mesocosm system was developed to simulate estuarine conditions characteristic
      of short water-residence time ecosystems of the Pacific Coast of North America,
      and used to evaluate the response of multiple macrophyte metrics to gradients of
      NO3 loading and temperature. Replicated experiments found that few responses
      could be directly attributed to NO3 loading up to 6 x ambient. Some response
      metrics exhibited weak relationships with nutrient loading but could not be
      resolved with available statistical power. While direct nutrient responses were
      found for some species-specific metrics (e.g. green macroalgal growth and
      biomass, tissue N%, etc.), many patterns were confounded with temperature.
      Temperature generally had a larger effect on response metrics than did nutrient
      load. Experimental macrophyte communities exhibited community shifts consistent
      with the predicted effects of nutrient loading at 20  degrees C, but there was no
      evidence of other eutrophication symptoms (phytoplankton blooms or hypoxia) due
      to the short system-residence time. The Z. marina Nutrient Pollution Index (NPI)
      tracked the NO3 gradient at 10  degrees C, but exhibited no response at 20 
      degrees C, which may limit the utility of this metric in areas with marked
      thermal seasonality. Results suggest that teasing apart the influence of
      temperature and nutrients on the expression of eutrophication symptoms will
      require complex multi-stressor experiments and the use of indicators that are
      sensitive across a broad range of conditions.

PMID- 29225372
TI  - Demystifying Spasticity: Reply to Dietz.

PMID- 29225371
TI  - Breaking the prejudice habit: Mechanisms, timecourse, and longevity.
AB  - The prejudice habit-breaking intervention (Devine et al., 2012) and its offshoots
      (e.g., Carnes et al., 2012) have shown promise in effecting long-term change in
      key outcomes related to intergroup bias, including increases in awareness,
      concern about discrimination, and, in one study, long-term decreases in implicit
      bias. This intervention is based on the premise that unintentional bias is like a
      habit that can be broken with sufficient motivation, awareness, and effort. We
      conducted replication of the original habit-breaking intervention experiment in a
      sample more than three times the size of the original (N = 292). We also measured
      all outcomes every other day for 14 days and measured potential mechanisms for
      the intervention's effects. Consistent with previous results, the habit-breaking
      intervention produced a change in concern that endured two weeks post
      intervention. These effects were associated with increased sensitivity to the
      biases of others and an increased tendency to label biases as wrong. Contrasting
      with the original work, both control and intervention participants decreased in
      implicit bias, and the effects of the habit-breaking intervention on awareness
      declined in the second week of the study. In a subsample recruited two years
      later, intervention participants were more likely than control participants to
      object on a public online forum to an essay endorsing racial stereotyping. Our
      results suggest that the habit-breaking intervention produces enduring changes in
      peoples' knowledge of and beliefs about race-related issues, and we argue that
      these changes are even more important for promoting long-term behavioral change
      than are changes in implicit bias.

PMID- 29225373
TI  - Line intensities and temperature-dependent line broadening coefficients of Q
      branch transitions in the v2 band of ammonia near 10.4 MUm.
AB  - We report measured line intensities and temperature-dependent broadening
      coefficients of NH3 with Ar, N2, O2, CO2, H2O, and NH3 for nine sQ(J,K)
      transitions in the nu2 fundamental band in the frequency range 961.5-967.5 cm-1.
      This spectral region was chosen due to the strong NH3 absorption strength and
      lack of spectral interference from H2O and CO2 for laser-based sensing
      applications. Spectroscopic parameters were determined by multi-line fitting
      using Voigt lineshapes of absorption spectra measured with two quantum cascade
      lasers in thermodynamically-controlled optical cells. The temperature dependence
      of broadening was measured over a range of temperatures between 300 and 600 K.
      These measurements aid the development of mid-infrared NH3 sensors for a broad
      range of gas mixtures and at elevated temperatures.

PMID- 29225374
TI  - Theory of Biopolymer Stretching at High Forces.
AB  - We provide a unified theory for the high force entropic elasticity of biopolymers
      solely in terms of the persistence length, xip , and the monomer spacing, a. When
      the force f>F h ~ kBTxip /a2 the biopolymers behave as freely jointed chains
      (FJCs) while in the range F l ~ kBT/xip <f<F h the worm-like chain (WLC) is a
      better model. We show that xip can be estimated from the force extension curve
      (FEC) at the extension x ~ 1/2 (normalized by the contour length of the
      biopolymer). After validating the theory using simulations, we provide a
      quantitative analysis of the FECs for a diverse set of biopolymers (dsDNA, ssRNA,
      ssDNA, polysaccharides, and unstructured PEVK domain of titin) for x >= 1/2. The
      success of a specific polymer model (FJC or WLC) to describe the FEC of a given
      biopolymer is naturally explained by the theory. Only by probing the response of
      biopolymers over a wide range of forces can the f-dependent elasticity be fully
      described.

PMID- 29225375
TI  - Folded concave penalized sparse linear regression: sparsity, statistical
      performance, and algorithmic theory for local solutions.
AB  - This paper concerns the folded concave penalized sparse linear regression
      (FCPSLR), a class of popular sparse recovery methods. Although FCPSLR yields
      desirable recovery performance when solved globally, computing a global solution
      is NP-complete. Despite some existing statistical performance analyses on local
      minimizers or on specific FCPSLR-based learning algorithms, it still remains open
      questions whether local solutions that are known to admit fully polynomial-time
      approximation schemes (FPTAS) may already be sufficient to ensure the statistical
      performance, and whether that statistical performance can be non-contingent on
      the specific designs of computing procedures. To address the questions, this
      paper presents the following threefold results: (i) Any local solution
      (stationary point) is a sparse estimator, under some conditions on the parameters
      of the folded concave penalties. (ii) Perhaps more importantly, any local
      solution satisfying a significant subspace second-order necessary condition
      (S3ONC), which is weaker than the second-order KKT condition, yields a bounded
      error in approximating the true parameter with high probability. In addition, if
      the minimal signal strength is sufficient, the S3ONC solution likely recovers the
      oracle solution. This result also explicates that the goal of improving the
      statistical performance is consistent with the optimization criteria of
      minimizing the suboptimality gap in solving the non-convex programming
      formulation of FCPSLR. (iii) We apply (ii) to the special case of FCPSLR with
      minimax concave penalty (MCP) and show that under the restricted eigenvalue
      condition, any S3ONC solution with a better objective value than the Lasso
      solution entails the strong oracle property. In addition, such a solution
      generates a model error (ME) comparable to the optimal but exponential-time
      sparse estimator given a sufficient sample size, while the worst-case ME is
      comparable to the Lasso in general. Furthermore, to guarantee the S3ONC admits
      FPTAS.

PMID- 29225376
TI  - Heterodyne detection with mismatch correction based on array detector.
AB  - Based on an array detector, a new heterodyne detection system, which can correct
      the mismatches of amplitude and phase between signal and local oscillation (LO)
      beams, is presented in this paper. In the light of the fact that, for a
      heterodyne signal, there is a certain phase difference between the adjacent two
      samples of analog-to-digital converter (ADC), we propose to correct the spatial
      phase mismatch by use of the time-domain phase difference. The corrections can be
      realized by shifting the output sequences acquired from the detector elements in
      the array, and the steps of the shifting depend on the quantity of spatial phase
      mismatch. Numerical calculations of heterodyne efficiency are conducted to
      confirm the excellent performance of our system. Being different from previous
      works, our system needs not extra optical devices, so it provides probably an
      effective means to ease the problem resulted from the mismatches.

PMID- 29225377
TI  - OCT imaging with temporal dispersion induced intense and short coherence laser
      source.
AB  - Lower coherence length and higher intensity are two indispensable requirements on
      the light source for high resolution and large penetration depth OCT imaging.
      While tremendous interest is being paid on engineering various laser sources to
      enlarge their bandwidth and hence lowering the coherence length, here we
      demonstrate another approach by employing strong temporal dispersion onto the
      existing laser source. Cholesteric liquid crystal (CLC) cells with suitable
      dispersive slope at the edge of 1-D organic photonic band gap have been designed
      to provide maximum reduction in coherence volume while maintaining the intensity
      higher than 50%. As an example, the coherence length of a multimode He-Ne laser
      is reduced by more than 730 times.

PMID- 29225378
TI  - Intensive ground vegetation growth mitigates the carbon loss after forest
      disturbance.
AB  - Aims: Slow or failed tree regeneration after forest disturbance is increasingly
      observed in the central European Alps, potentially amplifying the carbon (C) loss
      from disturbance. We aimed at quantifying C dynamics of a poorly regenerating
      disturbance site with a special focus on the role of non-woody ground vegetation.
      Methods: Soil CO2 efflux, fine root biomass, ground vegetation biomass, tree
      increment and litter input were assessed in (i) an undisturbed section of a ~ 110
      years old Norway spruce stand, (ii) in a disturbed section which was clear-cut
      six years ago (no tree regeneration), and (iii) in a disturbed section which was
      clear-cut three years ago (no tree regeneration). Results: Total soil CO2 efflux
      was similar across all stand sections (8.5 +/- 0.2 to 8.9 +/- 0.3 t C ha-1 yr.
      1). The undisturbed forest served as atmospheric C sink (2.1 t C ha-1 yr.-1),
      whereas both clearings were C sources to the atmosphere. The source strength
      three years after disturbance (-5.5 t C ha-1 yr.-1) was almost twice as high as
      six years after disturbance (-2.9 t C ha-1 yr.-1), with declining heterotrophic
      soil respiration and the high productivity of dense graminoid ground vegetation
      mitigating C loss. Conclusions: C loss after disturbance decreases with time and
      ground vegetation growth. Dense non-woody ground vegetation cover can hamper tree
      regeneration but simultaneously decrease the ecosystem C loss. The role of ground
      vegetation should be more explicitly taken into account in forest C budgets
      assessing disturbance effects.

PMID- 29225380
TI  - Performance of Anaerobic Biotrickling Filter and its Microbial Diversity for the
      Removal of Stripped Disinfection Byproducts.
AB  - The objective of this research was to evaluate the biodegradation of chloroform
      by using biotrickling filter (BTF) and determining the dominant bacteria
      responsible for the degradation. The research was conducted in three phases under
      anaerobic condition, namely, in the presence of co-metabolite (Phase I), in the
      presence of co-metabolite and surfactant (Phase II) and in the presence of
      surfactant but no co-metabolite (Phase III). The results showed that the presence
      of ethanol as a co-metabolite provided 49% removal efficiency. The equivalent
      elimination capacity (EC) was 0.13 g/(m3.hr). The addition of Tomadol 25 - 7 as a
      surfactant in the nutrient solution increased the removal efficiency of
      chloroform to 64% with corresponding EC of 0.17 g/(m3.hr). This research also
      investigated the overall microbial ecology of the BTF utilizing culture
      independent gene sequencing alignment of the 16S rRNA allowing identification of
      isolated species. Taxonomical composition revealed the abundance of
      deltaproteobacteria and deltaproteobacteria with species level of 97%. A. oryzae
      (formally dechlorosoma suillum), A. restrica and Geobacter spp. together with
      other similar groups were the most valuable bacteria for the degradation of
      chloroform.

PMID- 29225379
TI  - Tailoring Trehalose for Biomedical and Biotechnological Applications.
AB  - Trehalose is a non-reducing sugar whose ability to stabilize biomolecules has
      brought about its widespread use in biological preservation applications.
      Trehalose is also an essential metabolite in a number of pathogens, most
      significantly the global pathogen Mycobacterium tuberculosis, though it is absent
      in humans and other mammals. Recently, there has been a surge of interest in
      modifying the structure of trehalose to generate analogues that have applications
      in biomedical research and biotechnology. Non-degradable trehalose analogues
      could have a number of advantages as bioprotectants and food additives. Trehalose
      based imaging probes and inhibitors are already useful as research tools and may
      have future value in the diagnosis and treatment of tuberculosis, among other
      uses. Underlying the advancements made in these areas are novel synthetic methods
      that facilitate access to and evaluation of trehalose analogues. In this review,
      we focus on both aspects of the development of this class of molecules. First, we
      consider the chemical and chemoenzymatic methods that have been used to prepare
      trehalose analogues and discuss their prospects for synthesis on commercially
      relevant scales. Second, we describe ongoing efforts to develop and deploy
      detectable trehalose analogues, trehalose-based inhibitors, and non-digestible
      trehalose analogues. The current and potential future uses of these compounds are
      discussed, with an emphasis on their roles in understanding and combatting
      mycobacterial infection.

PMID- 29225381
TI  - Linking bacterial community structure to advection and environmental impact along
      a coast-fjord gradient of the Sognefjord, western Norway.
AB  - Here we present novel data on bacterial assemblages along a coast-fjord gradient
      in the Sognefjord, the deepest (1308 m) and longest (205 km) ice-free fjord in
      the world. Data were collected on two cruises, one in November 2012, and one in
      May 2013. Special focus was on the impact of advective processes and how these
      are reflected in the autochthonous and allochthonous fractions of the bacterial
      communities. Both in November and May bacterial community composition, determined
      by Automated Ribosomal Intergenic Spacer Analyses (ARISA), in the surface and
      intermediate water appeared to be highly related to bacterial communities
      originating from freshwater runoff and coastal water, whereas the sources in the
      basin water were mostly unknown. Additionally, the inner part of the Sognefjord
      was more influenced by side-fjords than the outer part, and changes in bacterial
      community structure along the coast-fjord gradient generally showed higher
      correlation with environmental variables than with geographic distances. High
      resolution model simulations indicated a surprisingly high degree of temporal and
      spatial variation in both current speed and direction. This led to a more
      episodic/discontinuous horizontal current pattern, with several vortices (10-20
      km wide) being formed from time to time along the fjord. We conclude that during
      periods of strong wind forcing, advection led to allochthonous species being
      introduced to the surface and intermediate layers of the fjord, and also appeared
      to homogenize community composition in the basin water. We also expect vortices
      to be active mixing zones where inflowing bacterial populations on the southern
      side of the fjord are mixed with the outflowing populations on the northern side.
      On average, retention time of the fjord water was sufficient for bacterial
      communities to be established.

PMID- 29225382
TI  - Associations between Responsible Beverage Service Laws and Binge Drinking and
      Alcohol-Impaired Driving.
AB  - We explored potential associations between the strength of state Responsible
      Beverage Service (RBS) laws and self-reported binge drinking and alcohol-impaired
      driving in the U.S. A multilevel logistic mixed-effects model was used, adjusting
      for potential confounders. Analyses were conducted on the overall BRFSS sample
      and drinkers only. Seven percent of BRFSS respondents lived in states with the
      strongest RBS laws, 15% reported binge drinking and 2% reported driving after
      having too much to drink at least once in the past 30 days. There was no evidence
      of a significant association between RBS law strength and self-reported binge
      drinking or alcohol-impaired driving. Future studies should include additional
      information about RBS laws and use a prospective research design.

PMID- 29225383
TI  - Assessment of Risk and Protection in Native American Youth: Steps Toward
      Conducting Culturally Relevant, Sustainable Prevention in Indian Country.
AB  - Background: This study constitutes a building block in the cultural adaptation of
      Communities That Care (CTC), a community-based prevention system that has been
      found to be effective in reducing youth problem behaviors. Methods: Using the
      data from the CTC normative survey dataset that consists of more than quarter
      million youth nationwide, this study examines the reliability and validity of
      scores derived from the Communities That Care Youth Survey (CTC-YS), one of the
      primary assessment tools for gathering community data on risk and protective
      factors related to problem behaviors including substance use. The reliability and
      criterion validity analyses are conducted overall for the nationwide sample of
      youth as well as for the student subsample of Native American youth. Results: The
      results of this study indicate that the existing CTC-YS assessments of risk and
      protective factors in the domains of community, family, school, and peer groups
      as well as within individuals yield scores that are reliable and valid within the
      Native American sample of youth. Conclusions: This study informs the third step
      in the CTC prevention planning process, which involves the assessment of risk and
      protective factors to be targeted in preventive interventions. The question of
      how the assessment of risk and protective factors among Native American youth
      might be further improved and a description of efforts related to the cultural
      adaptation of the CTC program currently underway are also addressed in the
      discussion.

PMID- 29225384
TI  - The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In
      Situ Measurements in the Tropical Lower Stratosphere.
AB  - Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that
      may be intentionally enhanced in the future to offset greenhouse gases
      (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in
      maintaining background SAs has been debated for decades without in-situ
      measurements of SO2 at the tropical tropopause to inform this issue. Here we
      clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements
      to evaluate climate models and satellite retrievals. We then use the observed
      tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across
      the tropical tropopause. These analyses show that the tropopause background SO2
      is about 5 times smaller than reported by the average satellite observations that
      have been used recently to test atmospheric models. This shifts the view of SO2
      as a dominant source of SAs to a near-negligible one, possibly revealing a
      significant gap in the SA budget.

PMID- 29225385
TI  - Extrinsic local regression on manifold-valued data.
AB  - We propose an extrinsic regression framework for modeling data with manifold
      valued responses and Euclidean predictors. Regression with manifold responses has
      wide applications in shape analysis, neuroscience, medical imaging and many other
      areas. Our approach embeds the manifold where the responses lie onto a higher
      dimensional Euclidean space, obtains a local regression estimate in that space,
      and then projects this estimate back onto the image of the manifold. Outside the
      regression setting both intrinsic and extrinsic approaches have been proposed for
      modeling i.i.d manifold-valued data. However, to our knowledge our work is the
      first to take an extrinsic approach to the regression problem. The proposed
      extrinsic regression framework is general, computationally efficient and
      theoretically appealing. Asymptotic distributions and convergence rates of the
      extrinsic regression estimates are derived and a large class of examples are
      considered indicating the wide applicability of our approach.

PMID- 29225386
TI  - "I don't want to grow up, I'm a [Gen X, Y, Me] kid": Increasing maturity fears
      across the decades.
AB  - The current studies examined the hypothesis that maturity fears are increasing
      among undergraduate men and women from the United States over time. Study 1 used
      a time-lag method to assess generational effects of maturity fears among a large
      sample (n = 3,291) of undergraduate men and women assessed in 1982, 1992, 2002,
      and 2012. Results revealed that both men and women reported significantly higher
      rates of maturity fears across time. Study 2 replicated these findings, and used
      a more restricted time frame to more closely examine the rate of change.
      Undergraduate women (n = 554) were assessed in 2001, 2003, 2009, and 2012.
      Maturity fears were again found to increase from 2001 to 2012. Recent cohorts of
      emerging adults seem more reluctant to mature than previous cohorts. Many
      contributing factors may be at play, including challenging economic times, social
      pressures to remain youthful, and/or internal fears of assuming increased
      responsibility.

PMID- 29225387
TI  - Exploiting soft organic optical resonant structure towards large range electro
      optic tunable devices.
AB  - Very fine molecular arrangement of cholesteric liquid crystal (CLC), can be
      compressed by applying an external electric field in the liquid crystal cell
      geometry. This enables very fine tuning of the wavelength of the reflected light.
      The compression of the periodic dielectric molecular arrangement continues till
      the chiral energy density meets its repulsive-type excluded volume interaction
      and hence the corresponding resonant wavelength jumps back to the original
      spectral position. Experimentally, the tuning range is observed to be highly
      affected by the concentration of the chiral dopant in the mixture. Analytically,
      it is shown that, use of chiral molecules with higher helical twisting power
      (HTP) can reduce the concentration of the chiral dopant for a desired pitch
      length in visible range and hence, the spectral tuning can be exploited over the
      entire visible range.

PMID- 29225388
TI  - Latent classes of older foster youth: Prospective associations with outcomes and
      exits from the foster care system during the transition to adulthood.
AB  - Youth in the foster care system face considerable challenges during the
      transition to adulthood. However, there is significant variability within this
      population. This study uses person-oriented methods and a longitudinal dataset of
      youth aging out of foster care to examine differences in how subgroups of foster
      youth fare during the transition to adulthood. We identified four distinct latent
      classes, consistent with prior person-oriented studies of this population, and
      validated these classes by examining differences on additional relevant factors
      at age 17. After establishing these classes, we tested their predictive validity
      by examining differences in outcomes at age 19 in domains relevant to the
      transition to adulthood, including education and employment, problem behaviors,
      and mental health problems. Finally, given the importance of extended foster care
      in promoting better outcomes, we used survival analysis to prospectively examine
      whether class membership was associated with differences in the rates at which
      youth left foster care between ages 17 and 19. One large group of youth exhibited
      moderate behavior problems and left care quickly, while another large group of
      resilient youth had favorable outcomes and left care relatively slowly. A small
      group exhibited considerable behavior and mental health problems, but left care
      more slowly, and a very small group was characterized by a history of pregnancy.
      Findings suggest considerable variability in service need among older foster
      youth. Implications for service provision during the transition to adulthood are
      discussed.

PMID- 29225389
TI  - Parenting Attitudes, Family Environments, Depression, and Anxiety in Caregivers
      of Maltreated Children.
AB  - This study evaluated parenting attitudes, family environments, depression, and
      anxiety in a sample of primarily minority urban mothers to better understand
      maltreating mothers (n = 83), who retain custody of their children and how they
      are similar to and different from foster mothers (n = 50), kin caregivers (n =
      52) of maltreated children, and comparison mothers (n = 100) from the same
      communities. Maltreating mothers were distinguished by their much higher levels
      of depression and anxiety from other mothers. In addition, like foster mothers,
      maltreating mothers were less likely to approve of corporal punishment. Foster
      mothers were higher in organization and lower in empathy than other groups. There
      were no differences by race/ethnicity on study dimensions. Higher education,
      however, was related to more favorable parenting attitudes and family
      environments. Practice implications related to appropriate services are
      suggested.

PMID- 29225390
TI  - Immigrant Bilingualism in Spain: An Asset or a Liability?
AB  - This study contributes to the ongoing debate about bilingual advantage and
      examines whether bilingual immigrant youths fare better, as well as, or worse
      academically than the matching group of monolinguals. Using data from Spain,
      where close to half of immigrants speak Spanish as their native language, we
      found no evidence of costs of bilingualism: bilingual youths did benefit from
      their linguistic skills. Their advantage, however, manifested itself not
      uniformly across discrete outcomes, but in a direct trajectory toward higher
      educational attainment. Bilingualism neutralized the possible negative effect of
      ethnic origins and extended the positive effect of high parental ambition.
      Implications for theory and practice are discussed.

PMID- 29225391
TI  - Early Intervention for Preschoolers at Risk for Attention-Deficit/Hyperactivity
      Disorder: Preschool First Step to Success.
AB  - This study evaluated the efficacy of the Preschool First Step (PFS) to Success
      early intervention for children at risk for attention deficit hyperactivity
      disorder (ADHD). PFS is a targeted intervention for children 3-5 years old with
      externalizing behavior problems and addresses secondary prevention goals and
      objectives. As part of a larger multisite, randomized controlled trial, the
      efficacy of the PFS program was evaluated on a subsample of 45 children who also
      had elevated comorbid ADHD symptoms as rated by parents and teachers. The PFS
      program was found to produce significantly higher social skills, and
      significantly fewer behavior problems across a variety of teacher-and parent
      reported measures at postintervention. Effect sizes for teacher-reported effects
      were large across a variety of social competency indicators, including those
      specific to ADHD. Effect sizes for parent-reported social skills and problem
      behaviors were medium. Although not specifically designed for preschoolers at
      risk for comorbid ADHD, this generic behavioral intervention appeared to be
      successful for this population. Implications and limitations of the study are
      discussed.

PMID- 29225392
TI  - A COMPUTATIONAL ANALYSIS OF BONE FORMATION IN THE CRANIAL VAULT USING A COUPLED
      REACTION-DIFFUSION-STRAIN MODEL.
AB  - Bones of the murine cranial vault are formed by differentiation of mesenchymal
      cells into osteoblasts, a process that is primarily understood to be controlled
      by a cascade of reactions between extracellular molecules and cells. We assume
      that the process can be modeled using Turing's reaction-diffusion equations, a
      mathematical model describing the pattern formation controlled by two interacting
      molecules (activator and inhibitor). In addition to the processes modeled by
      reaction-diffusion equations, we hypothesize that mechanical stimuli of the cells
      due to growth of the underlying brain contribute significantly to the process of
      cell differentiation in cranial vault development. Structural analysis of the
      surface of the brain was conducted to explore the effects of the mechanical
      strain on bone formation. We propose a mechanobiological model for the formation
      of cranial vault bones by coupling the reaction-diffusion model with structural
      mechanics. The mathematical formulation was solved using the finite volume
      method. The computational domain and model parameters are determined using a
      large collection of experimental data that provide precise three dimensional (3D)
      measures of murine cranial geometry and cranial vault bone formation for specific
      embryonic time points. The results of this study suggest that mechanical strain
      contributes information to specific aspects of bone formation. Our
      mechanobiological model predicts some key features of cranial vault bone
      formation that were verified by experimental observations including the relative
      location of ossification centers of individual vault bones, the pattern of
      cranial vault bone growth over time, and the position of cranial vault sutures.

PMID- 29225393
TI  - Implicit and Explicit Communal Coping in Couples with Recently Diagnosed Type 2
      Diabetes.
AB  - When an individual in a close relationship is diagnosed with a chronic illness,
      coping can be the responsibility of the patient, or couple-members can cope
      communally. Communal coping reflects a shared appraisal of a stressor (our
      problem instead of my problem) and collaborative efforts to address the stressor.
      The current study examined whether patients' and partners' communal coping levels
      were associated with relational and health functioning among 70 couples in which
      one member was recently diagnosed with type 2 diabetes. We assessed explicit
      communal coping with self-reported "inclusion of the other in the self" in regard
      to diabetes management and implicit communal coping with first person plural
      pronoun usage during a diabetes discussion. We also assessed patient reports of
      support received from partners, patient and partner psychological distress, and
      patient self-care behavior. Results showed that patient explicit communal coping
      was related to better patient relationship quality and greater support receipt
      from partners. Patient and partner explicit communal coping also were related to
      reduced partner distress but not patient distress. Instead, partner implicit
      communal coping was related to reduced patient distress. Most noteworthy, partner
      implicit communal coping was related to better patient self-care behavior. These
      results suggest that communal coping may be beneficial for both relationships and
      health, but that the effects of explicit measures differ from those of implicit
      measures. Patients might benefit especially from partner communal coping efforts
      that are less obvious.

PMID- 29225395
TI  - Review: Water recovery from brines and salt-saturated solutions: operability and
      thermodynamic efficiency considerations for desalination technologies.
AB  - BACKGROUND: When water is recovered from a saline source, a brine concentrate
      stream is produced. Management of the brine stream can be problematic,
      particularly in inland regions. An alternative to brine disposal is recovery of
      water and possibly salts from the concentrate. RESULTS: This review provides an
      overview of desalination technologies and discusses the thermodynamic
      efficiencies and operational issues associated with the various technologies
      particularly with regard to high salinity streams. CONCLUSION: Due to the high
      osmotic pressures of the brine concentrates, reverse osmosis, the most common
      desalination technology, is impractical. Mechanical vapor compression which, like
      reverse osmosis, utilizes mechanical work to operate, is reported to have the
      highest thermodynamic efficiency of the desalination technologies for treatment
      of salt-saturated brines. Thermally-driven processes, such as flash evaporation
      and distillation, are technically able to process saturated salt solutions, but
      suffer from low thermodynamic efficiencies. This inefficiency could be offset if
      an inexpensive source of waste or renewable heat could be used. Overarching
      issues posed by high salinity solutions include corrosion and the formation of
      scales/precipitates. These issues limit the materials, conditions, and unit
      operation designs that can be used.

PMID- 29225394
TI  - Parents and partners: Moderating and mediating influences on intimate partner
      violence across adolescence and young adulthood.
AB  - Prior work examining intimate partner violence (IPV) among young adults often has
      emphasized familial characteristics, such as parent-child physical aggression
      (PCPA), and romantic relationship dynamics, such as jealousy and controlling
      behaviors, but has not considered these two domains simultaneously. Likewise,
      research examining how these two domains affect IPV perpetration over time for
      young adults is still limited. Using five waves of data from the Toledo
      Adolescent Relationships Study (N = 950), the present study examined the
      influence of parent-child relationship factors and romantic relationship dynamics
      in both their main and interactive effects on IPV perpetration spanning
      adolescence through young adulthood. Results from random-effects analyses
      indicated that both familial and romantic relationship dynamics should be taken
      into account when predicting IPV perpetration. Importantly, these two domains
      interacted to produce cumulatively different risk for engaging in violence
      against a romantic partner. Individuals were more likely to perpetrate IPV when
      their romantic relationship was characterized by verbal aggression if they
      reported PCPA experiences.

PMID- 29225396
TI  - New Students' Peer Integration and Exposure to Deviant Peers: Spurious Effects of
      School Moves?
AB  - School moves during adolescence predict lower peer integration and higher
      exposure to delinquent peers. Yet mobility and peer problems have several common
      correlates, so differences in movers' and non-movers' social adjustment may be
      due to selection rather than to causal effects of school moves. Drawing on survey
      and social network data from a sample of 7th and 8th graders, this study compared
      the structure and behavioral content of new students' friendship networks to
      those of not only non-movers, but also of students about to move schools; the
      latter should resemble new students in both observed and unobserved ways. The
      results suggest that the association between school moves and friends'
      delinquency is due to selection, but the association between school moves and
      peer integration may not be entirely due to selection.

PMID- 29225397
TI  - Concurrent OCT imaging of stimulus evoked retinal neural activation and
      hemodynamic responses.
AB  - It is well established that major retinal diseases involve distortions of the
      retinal neural physiology and blood vascular structures. However, the details of
      distortions in retinal neurovascular coupling associated with major eye diseases
      are not well understood. In this study, a multi-modal optical coherence
      tomography (OCT) imaging system was developed to enable concurrent imaging of
      retinal neural activity and vascular hemodynamics. Flicker light stimulation was
      applied to mouse retinas to evoke retinal neural responses and hemodynamic
      changes. The OCT images were acquired continuously during the pre-stimulation,
      light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical
      signals (IOSs) and hemodynamic changes were observed over time in blood-free and
      blood regions, respectively. Rapid IOSs change occurred almost immediately after
      stimulation. Both positive and negative signals were observed in adjacent retinal
      areas. The hemodynamic changes showed time delays after stimulation. The signal
      magnitudes induced by light stimulation were observed in blood regions and did
      not show significant changes in blood-free regions. These differences may arise
      from different mechanisms in blood vessels and neural tissues in response to
      light stimulation. These characteristics agreed well with our previous
      observations in mouse retinas. Further development of the multi-modal OCT may
      provide a new imaging method for studying how retinal structures and metabolic
      and neural functions are affected by age-related macular degeneration (AMD),
      glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel
      noninvasive biomarkers for early disease detection and reliable treatment
      evaluations of eye diseases.

PMID- 29225398
TI  - Update on Bio-Refining and Nanocellulose Composite Materials Manufacturing.
AB  - Nanocellulose is a high value material that has gained increasing attention
      because of its high strength, stiffness, unique photonic and piezoelectric
      properties, high stability and uniform structure. One of the factors limiting the
      potential of nanocellulose and the vast array of potential new products is the
      ability to produce high-volume quantities of this nano-material. However, recent
      research has demonstrated that nanocellulose can be efficently produced in large
      volumes from wood at relatively low cost by the incorporation of ionizing
      radiation in the process stream. Ionizing radiation causes significant break down
      of the polysaccharides and leads to the production of potentially useful gaseous
      products such as H2 and CO. Ionizing radiation processing remains an open field,
      ripe for innovation and application. This presentation will review the strong
      collaboration between the National Institute of Standards and Technology (NIST)
      and its academic partners pursuing the demonstration of applied ionizing
      radiation processing to plant materials for the manufacturing and
      characterization of novel nanomaterials.

PMID- 29225399
TI  - Endoscopic-CT: Learning-Based Photometric Reconstruction for Endoscopic Sinus
      Surgery.
AB  - In this work we present a method for dense reconstruction of anatomical
      structures using white light endoscopic imagery based on a learning process that
      estimates a mapping between light reflectance and surface geometry. Our method is
      unique in that few unrealistic assumptions are considered (i.e., we do not assume
      a Lambertian reflectance model nor do we assume a point light source) and we
      learn a model on a per-patient basis, thus increasing the accuracy and
      extensibility to different endoscopic sequences. The proposed method assumes
      accurate video-CT registration through a combination of Structure-from-Motion
      (SfM) and Trimmed-ICP, and then uses the registered 3D structure and motion to
      generate training data with which to learn a multivariate regression of observed
      pixel values to known 3D surface geometry. We demonstrate with a non-linear
      regression technique using a neural network towards estimating depth images and
      surface normal maps, resulting in high-resolution spatial 3D reconstructions to
      an average error of 0.53mm (on the low side, when anatomy matches the CT
      precisely) to 1.12mm (on the high side, when the presence of liquids causes scene
      geometry that is not present in the CT for evaluation). Our results are exhibited
      on patient data and validated with associated CT scans. In total, we processed
      206 total endoscopic images from patient data, where each image yields
      approximately 1 million reconstructed 3D points per image.

PMID- 29225400
TI  - Image-Based Navigation for Functional Endoscopic Sinus Surgery Using Structure
      From Motion.
AB  - Functional Endoscopic Sinus Surgery (FESS) is a challenging procedure for
      otolaryngologists and is the main surgical approach for treating chronic
      sinusitis, to remove nasal polyps and open up passageways. To reach the source of
      the problem and to ultimately remove it, the surgeons must often remove several
      layers of cartilage and tissues. Often, the cartilage occludes or is within a few
      millimeters of critical anatomical structures such as nerves, arteries and ducts.
      To make FESS safer, surgeons use navigation systems that register a patient to
      his/her CT scan and track the position of the tools inside the patient. Current
      navigation systems, however, suffer from tracking errors greater than 1 mm, which
      is large when compared to the scale of the sinus cavities, and errors of this
      magnitude prevent from accurately overlaying virtual structures on the endoscope
      images. In this paper, we present a method to facilitate this task by 1)
      registering endoscopic images to CT data and 2) overlaying areas of interests on
      endoscope images to improve the safety of the procedure. First, our system uses
      structure from motion (SfM) to generate a small cloud of 3D points from a short
      video sequence. Then, it uses iterative closest point (ICP) algorithm to register
      the points to a 3D mesh that represents a section of a patients sinuses. The
      scale of the point cloud is approximated by measuring the magnitude of the
      endoscope's motion during the sequence. We have recorded several video sequences
      from five patients and, given a reasonable initial registration estimate, our
      results demonstrate an average registration error of 1.21 mm when the endoscope
      is viewing erectile tissues and an average registration error of 0.91 mm when the
      endoscope is viewing non-erectile tissues. Our implementation SfM + ICP can
      execute in less than 7 seconds and can use as few as 15 frames (0.5 second of
      video). Future work will involve clinical validation of our results and
      strengthening the robustness to initial guesses and erectile tissues.

PMID- 29225401
TI  - Weight Smoothing for Generalized Linear Models Using a Laplace Prior.
AB  - When analyzing data sampled with unequal inclusion probabilities, correlations
      between the probability of selection and the sampled data can induce bias if the
      inclusion probabilities are ignored in the analysis. Weights equal to the inverse
      of the probability of inclusion are commonly used to correct possible bias. When
      weights are uncorrelated with the descriptive or model estimators of interest,
      highly disproportional sample designs resulting in large weights can introduce
      unnecessary variability, leading to an overall larger mean square error compared
      to unweighted methods. We describe an approach we term 'weight smoothing' that
      models the interactions between the weights and the estimators as random effects,
      reducing the root mean square error (RMSE) by shrinking interactions toward zero
      when such shrinkage is allowed by the data. This article adapts a flexible
      Laplace prior distribution for the hierarchical Bayesian model to gain a more
      robust bias-variance tradeoff than previous approaches using normal priors.
      Simulation and application suggest that under a linear model setting, weight
      smoothing models with Laplace priors yield robust results when weighting is
      necessary, and provide considerable reduction in RMSE otherwise. In logistic
      regression models, estimates using weight-smoothing models with Laplace priors
      are robust, but with less gain in efficiency than in linear regression settings.

PMID- 29225402
TI  - Behavioral assay and chemical characters of female sex pheromones in the hermit
      crab Pagurus filholi.
AB  - Males of the hermit crab Pagurus filholi perform assessment behavior toward
      females, as a preliminary step of precopulatory guarding, during the reproductive
      season. It is known that such behavior is elicited by female sex pheromones, but
      the compounds involved have never been characterized in this species. Several
      experiments were conducted to develop a reliable bioassay along with purification
      procedures to identify potential compounds with pheromonal activity in Pagurus
      filholi. We developed a bioassay protocol to assess pheromonal activity by using
      an empty shell with cotton containing either artificial seawater (control) or
      test water. We measured and compared the time duration of male assessment
      behavior toward each shell if the test water contained female sex pheromones.
      Ultra-filtering of seawater samples potentially containing pheromones showed that
      the compound was <1 kDa in molecular weight. Males showed precopulatory
      assessment behavior toward "female conditioned" water samples treated with open
      column purification and eluted with MeOH, suggesting that compounds triggering
      male behavior were low polar molecules. Molecules with pheromonal activity were
      not volatile after freeze drying, effective even after heating to 90  degrees C,
      and remained active in seawater at 12  degrees C even after 6 days from sample
      collection, which suggests a rather stable characteristic of the female sex
      pheromones of this species.

PMID- 29225403
TI  - Male mate choice in a sexually cannibalistic species: male escapes from hungry
      females in the praying mantid Tenodera angustipennis.
AB  - While competing males and choosy females may be common in animal mating systems,
      male choice can evolve under certain conditions. Sexual cannibalism is such a
      condition because of the high mortality risk for males. In mantids, female body
      condition is associated with male mate preference, with fat females preferred,
      due to at least two reasons: females in poor nutritional condition are likely to
      attack and predate males, and fat females can potentially increase the number of
      offspring. Thus, the risk of cannibalism and female fecundity can influence male
      mating behavior. In this study, we attempted to separate these factors by using
      the praying mantid Tenodera angustipennis to examine whether male preference for
      fat female mantids was based on avoiding sexual cannibalism (cannibalism
      avoidance hypothesis) or preference for female fecundity (fecundity preference
      hypothesis). The feeding regimes were experimentally manipulated to discriminate
      between the effects of female fecundity and female hunger status on male and
      female mating behaviors. We found that recently starved females more frequently
      locomoted toward the male, and that male abdominal bending was less intensive and
      escape was sooner from recently starved females. These female and male behavioral
      responses to female hunger condition may reveal male avoidance of dangerous
      females in this mantid.

PMID- 29225404
TI  - Setting an evolutionary trap: could the hider strategy be maladaptive for white
      tailed deer?
AB  - An evolutionary trap occurs when an organism makes a formerly adaptive decision
      that now results in a maladaptive outcome. Such traps can be induced by
      anthropogenic environmental changes, with nonnative species introductions being a
      leading cause. The recent establishment of coyotes (Canis latrans) into the
      southeastern USA has the potential to change white-tailed deer (Odocoileus
      virginianus) population dynamics through direct predation and behavioral
      adaptation. We used movement rate and bedsite characteristics of radiocollared
      neonates to evaluate their antipredator strategies in the context of novel
      predation risk in a structurally homogeneous, fire-maintained ecosystem. Neonate
      bedsites had greater plant cover values compared with random sites (t = 30.136; p
      < 0.001), indicating bedsite selection was consistent with the hider strategy
      used to avoid predation. We determined selection gradients of coyote predation on
      neonate movement rate and plant cover and diversity at bedsites during the first
      10 days of life. Interestingly, neonates that moved less and bedded in denser
      cover were more likely to be depredated by coyotes, meaning that greater neonate
      movement rate and bedsites located in less dense cover were favored by natural
      selection. These results are counter to expected antipredator strategies in white
      tailed deer and exemplify how an adaptive response could be maladaptive in novel
      contexts.

PMID- 29225405
TI  - Sometimes noise is beneficial: stream noise informs vocal communication in the
      little torrent frog Amolops torrentis.
AB  - Many kinds of environmental noise can interfere with acoustic communication and
      efficient decision making in terrestrial species. Here we identified an exception
      to this generalization in a streamside species, the little torrent frog (Amolops
      torrentis) which communicates in a stream noise environment. To determine whether
      stream noise can act as a cue regarding the microhabitat characteristics of
      senders, we performed phonotaxis experiments using stimulus pairs constructed
      with synthetic male calls (high or low dominant frequency) and stream noise with
      varied signal-to-noise ratios. We found that females prefer calls with high
      amplitude stream noise added compared to those with low amplitude stream noise
      added for both high and low dominant frequency stimulus pairs; however, stream
      noise itself was not attractive in the absence of calls. These results show that
      stream noise can function as a cue that may be used by females for enhancing the
      attractiveness of calls. Stream noise associates closely with rocks, topographies
      and vegetation and may thus provide useful microhabitat information for signal
      receivers, thereby acting on sexual selection. These data therefore contribute to
      our understanding of how the perception of mate attractiveness in heterogeneous
      ecological environments can evolve.

PMID- 29225406
TI  - Unique arm-flapping behavior of the pharaoh cuttlefish, Sepia pharaonis: putative
      mimicry of a hermit crab.
AB  - Cephalopods are able to control their arms sophisticatedly and use them for
      various behaviors, such as camouflage, startling predators and hunting prey.
      Here, we report a previously undescribed arm-flapping behavior of the pharaoh
      cuttlefish, Sepia pharaonis, observed in captivity. S. pharaonis raised the first
      pair of arms and wrinkled the parts near the distal end, where the skin color was
      darkened. Additionally, S. pharaonis spread the second and third pairs of arms
      and bent them as if they were jointed, and flapped the distal ends. S. pharaonis
      showed this behavior in two different situations: after being introduced into a
      large space, and during hunting. We discuss the putative functions of this
      behavior, including possible mimicry of a hermit crab, considering the situations
      in which the behavior was observed.

PMID- 29225407
TI  - Assessing type I error and power of multistate Markov models for panel data-A
      simulation study.
AB  - Ordinal outcomes collected at multiple follow-up visits are common in clinical
      trials. Sometimes, one visit is chosen for the primary analysis and the scale is
      dichotomized amounting to loss of information. Multistate Markov models describe
      how a process moves between states over time. Here, simulation studies are
      performed to investigate the type I error and power characteristics of multistate
      Markov models for panel data with limited non-adjacent state transitions. The
      results suggest that the multistate Markov models preserve the type I error and
      adequate power is achieved with modest sample sizes for panel data with limited
      non-adjacent state transitions.

PMID- 29225408
TI  - A simulation based method for assessing the statistical significance of logistic
      regression models after common variable selection procedures.
AB  - Classification models can demonstrate apparent prediction accuracy even when
      there is no underlying relationship between the predictors and the response.
      Variable selection procedures can lead to false positive variable selections and
      overestimation of true model performance. A simulation study was conducted using
      logistic regression with forward stepwise, best subsets, and LASSO variable
      selection methods with varying total sample sizes (20, 50, 100, 200) and numbers
      of random noise predictor variables (3, 5, 10, 15, 20, 50). Using our critical
      values can help reduce needless follow-up on variables having no true association
      with the outcome.

PMID- 29225409
TI  - School Context and American Indian Substance Use.
AB  - The present study extends prior research exploring the role of school contextual
      factors in predicting individual adolescent substance use by examining how a
      school's racial composition is associated with American Indian adolescent tobacco
      and marijuana use. Using a subsample of 523 American Indian students from the
      restricted use Add Health data, we consider both individual and school contextual
      factors across 99 schools. Our results suggest that a school's racial composition
      is associated with individual tobacco and marijuana use among American Indian
      youth, but in different ways depending upon the substance. Our findings
      illustrate the importance of extending research on the correlates of substance
      use for racial and ethnic minorities beyond studies examining African-Americans
      and/or Hispanics.

PMID- 29225410
TI  - Conformational Differentiation of alpha-Cyanohydroxycinnamic Acid Isomers: A
      Raman Spectroscopic Study.
AB  - Two alpha-cyanohydroxycinnamic acid positional isomers, alpha-cyano-4
      hydroxycinnamic acid (CHCA4) and alpha-cyano-3-hydroxycinnamic acid (CHCA3), were
      characterized using Raman spectroscopy. We analyzed the implications of the
      collected Raman spectral shifts, and verified them through other spectroscopic
      techniques, to arrive at plausible three dimensional structures of CHCA3 and
      CHCA4. The positions of these groups were mapped by systematically analyzing the
      orientation and type of interactions functional groups make in each CHCA isomer.
      We determined whether or not the carboxylic moieties are forming dimeric links
      and ascertained the existence of ring-ring pi-stacking interactions. We also
      assessed the nature of the hydrogen bonding between -CN and -OH groups. The
      results were then taken together to model plausible three dimensional structures
      for each compound. The data revealed a structure for CHCA4 that matches the
      published x-ray crystallographic structure. We then applied the same spectral
      analysis to CHCA3 to reveal its plausible three dimensional structure. The
      structural details revealed may account for the functional properties of the two
      alpha-cyanohydroxycinnamic acid positional isomers.

PMID- 29225411
TI  - Key Strategies for Building Research Capacity of University Faculty Members.
AB  - Universities are under pressure to increase external research funding, and some
      federal agencies offer programs to expand research capacity in certain kinds of
      institutions. However, conflicts within faculty roles and other aspects of
      university operations influence the effectiveness of particular strategies for
      increasing research activity. We review conventional approaches to increasing
      research, focusing on outcomes for individual faculty members and use one
      federally-funded effort to build cancer-related research capacity at a public
      university as an example to explore the impact of various strategies on research
      outcomes. We close with hypotheses that should be tested in future formal
      studies.

PMID- 29225412
TI  - Identity, Victimization, and Support: Facebook Experiences and Mental Health
      Among LGBTQ Youth.
AB  - The rise of social networking sites (SNSs) has created new contexts within which
      lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth and young adults
      manage their social identities and relationships. On one hand, SNSs provide
      important social support; on the other, they comprise another realm for
      victimization and discrimination. Context collapse refers to the ways diverse
      subgroups (e.g., family, co-workers) are often united in Facebook networks, which
      presents unique challenges related to outness. In this study, we examine the
      Facebook contexts of a cohort of LGBTQ youth and young adults with regard to
      outness, victimization, social support, and psychological distress by first
      examining descriptive statistics and correlations, and then testing a series of
      multiple regressions in an analytic sample of 175 (Mage = 24.02 years) LGBTQ
      youth. Participants reported levels of daily Facebook use comparable to other
      samples of non-LGBTQ youth; however, they reported greater use of security
      controls, which may function as a tool for managing outness. Participants
      reported slightly lower outness across relational subgroups on Facebook, and
      associations between outness to relational subgroups were slightly stronger on
      Facebook, illustrating the potential impact of context collapse. Regression
      results showed that great victimization, cyberbullying, and the offering of
      support online were positively associated with psychological distress. Study
      findings illuminate how LGBTQ youth use and manage their identities on Facebook
      and highlight the importance of online contexts in shaping wellbeing for LGBtQ
      outh and young adults.

PMID- 29225413
TI  - Outbreak of Hospital Infection from Biofilm-embedded Pan Drug-resistant
      Pseudomonas aeroginosa, Due to a Contaminated Bronchoscope.
AB  - Background: Colistin-resistant Pseudomonas aeruginosa (P. aeruginosa) has been
      defined as pandrug-resistant (PDR) strain. Outbreaks of PDR P. aeruginosa
      especially in pulmonary tract infections due to contaminated bronchoscopes have
      rarely been reported. The emergence of pandrug-resistant strains in both CF
      (Cystic Fibrosis) and non-CF clinical isolates over recent years remains of a
      great concern. Hospital wards contaminated with PDR P. aeruginosa infection, must
      be shot down until their eradication. Health Authorities must be informed
      immediately and infection control strategies must be implemented. Aim: To report
      such an outbreak and modify the infection control strategy in an academic
      hospital in Ankara Turkey. Methods: From October to December 2013, PDR
      Pseudomonas aerogionsa were identified from bronchial cultures of 15 patients who
      had undergone bronchoscopy prior to the infection. Three batches of surveillance
      cultures were obtained from the environmental objects and healthcare workers
      related to the procedures. Pulsed-field gel electrophoresis (PFGE) was used for
      bacterial typing. Antimicrobial susceptibility was assessed by disc diffusion and
      E-test methods. Findings: A total of 70 specimens were obtained during the first
      surveillance operation. One Colistin-resistant P. aeroginosa was isolated from a
      bronchoscope. Although the disinfection protocols for bronchoscope were revised
      and implemented, seven additional bronchial cases were identified thereafter. The
      pathogen was identified from two subsequent surveillance cultures and was not
      eliminated until Ethylene oxide sterilization was added to the disinfection
      protocol. PFGE revealed that all 15 isolates from the patients and the three
      isolates from the bronchoscope shared a common pattern with minor variance. XbaI
      restriction enzyme turned out better than SpeI in interpreting bacterial pulse
      types with BioNumerics 6.0. The most suitable cut off value for SpeI was above
      80% Dice similarity while for XbaI above 95%Dice similarity with BioNumerics 6.0.
      Conclusion: The outbreak of "Colistin" pan drug-resistant Pseudomonas aeroginosa
      was caused by a contaminated bronchoscope and was terminated by the
      implementation of a revised disinfection protocol for bronchoscope.

PMID- 29225414
TI  - Residual Sleep Problems Predict Reduced Response to Prolonged Exposure among
      Veterans with PTSD.
AB  - Objectives: While evidence-based treatments exist for posttraumatic stress
      disorder (PTSD), a significant sub-set of veterans continue to meet criteria for
      PTSD after treatment. Sleep problems may affect treatment retention and predict
      efficacy for PTSD treatments. Methods: The present study used data from a
      clinical trial of Prolonged Exposure therapy (PE) administered to veterans
      (N=154) to evaluate whether residual sleep symptoms remained after treatment
      completion, and if so, whether these residual sleep symptoms were associated with
      higher levels of PTSD and comorbid depression at the end of treatment.
      Participants (ages 20 to 75 years old; 35.7% Black; 54.5% married) completed
      demographic questions, symptom assessments, and engagement-related surveys.
      Results: Hierarchical multiple linear regression models demonstrated that changes
      in sleep were significant predictors of PTSD and depression symptom reduction
      above and beyond the influence of demographic and engagement factors (e.g.,
      therapy satisfaction). Conclusions: Greater residual sleep symptoms were
      predictive of smaller treatment gains. Findings illustrate the potential
      significance of sleep during the course of PTSD treatment, leading to several
      important clinical assessment and treatment implications.

PMID- 29225415
TI  - A Co-flow Structure for Goal-Directed Internal Change.
AB  - We describe a co-flow structure that models internal, goal-directed changes to an
      attribute (e.g., employee loyalty) of fundamental material (e.g., employees).
      This co-flow accommodates problems not adequately modeled with an existing,
      generic structure. Our structure builds on the co-flow proposed by Hines, which
      uses an information delay to model external change to an attribute. We use a
      first-order information delay to model both external changes to the attribute
      from the material stock and internal changes from an internal goal for the
      attribute. We provide an exact, dynamic solution for this co-flow enabling us to
      precisely describe its equilibrium and non-equilibrium behavior. Several examples
      are provided and discussed, including a situation where a management program is
      designed to increase average employee loyalty. In addition, we review
      applications of traditional and Hines co-flow structures to provide background
      and to describe our evolutionary path towards design of the new co-flow.

PMID- 29225416
TI  - Getting PEEK to Stick to Bone: The Development of Porous PEEK for Interbody
      Fusion Devices.
AB  - Interbody fusion cages are routinely implanted during spinal fusion procedures to
      facilitate arthrodesis of a degenerated or unstable vertebral segment. Current
      cages are most commonly made from polyether-ether-ketone (PEEK) due to its
      favorable mechanical properties and imaging characteristics. However, the smooth
      surface of current PEEK cages may limit implant osseointegration and may inhibit
      successful fusion. We present the development and clinical application of the
      first commercially available porous PEEK fusion cage (COHERE(r), Vertera, Inc.,
      Atlanta, GA) that aims to enhance PEEK osseointegration and spinal fusion
      outcomes. The porous PEEK structure is extruded directly from the underlying
      solid and mimics the structural and mechanical properties of trabecular bone to
      support bone ingrowth and implant fixation. Biomechanical testing of the
      COHERE(r) device has demonstrated greater expulsion resistance versus smooth PEEK
      cages with ridges and greater adhesion strength of porous PEEK versus plasma
      sprayed titanium coated PEEK surfaces. In vitro experiments have shown favorable
      cell attachment to porous PEEK and greater proliferation and mineralization of
      cell cultures grown on porous PEEK versus smooth PEEK and smooth titanium
      surfaces, suggesting that the porous structure enhances bone formation at the
      cellular level. At the implant level, preclinical animal studies have found
      comparable bone ingrowth into porous PEEK as those previously reported for porous
      titanium, leading to twice the fixation strength of smooth PEEK implants.
      Finally, two clinical case studies are presented demonstrating the effectiveness
      of the COHERE(r) device in cervical spinal fusion.

PMID- 29225417
TI  - Comparison of RAFT derived Poly(vinylpyrolidone) verses Poly(oligoethyleneglycol
      methacrylate) for the Stabilization of Glycosylated Gold Nanoparticles.
AB  - Carbohydrates dictate many biological processes including infection by pathogens.
      Glycosylated polymers and nanomaterials which have increased affinity due to the
      cluster glycoside effect, are therefore useful tools to probe function, but also
      as prophylactic therapies or diagnostic tools. Here, the effect of polymer
      structure on the coating of gold nanoparticles is studied in the context of
      grafting density, buffer stability and in a lectin binding assay. RAFT
      polymerization is used to generate poly(oligoethyleneglycol methacrylates) and
      poly(N-vinyl pyrolidones) with a thiol end-group for subsequent immobilization
      onto the gold. It is observed that poly(oligoethylene glycol methacrylates),
      despite being widely used particle coatings, lead to low grafting densities which
      in turn resulted in lower stability in biological buffers. A depression of the
      cloud point upon nanoparticle immobilization is also seen, which might compromise
      performance. In comparison poly(vinyl pyrolidones) resulted in stable particles
      with higher grafting densities due to the compact size of each monomer unit. The
      higher grafting density also enabled an increase in the number of carbohydrates
      which can be installed per nanoparticle at the chain ends, and gave increased
      binding in a lectin recognition assay. These results will guide the development
      of new nanoparticle biosensors with enhanced specificity, affinity and stability.

PMID- 29225418
TI  - Influence of Inbreeding on Female Mate Choice in Two Species of Drosophila.
AB  - Many organisms have been reported to choose their mates in order to increase the
      heterozygosity of their offspring by avoiding mating with relatives or homozygous
      individuals. Most previous studies using Drosophila melanogaster have used
      artificial chromosomes or extreme inbreeding treatments, situations unlikely to
      be matched in nature. Additionally, few studies have examined the interaction
      between female inbreeding status and her choice of mate. Using females and males
      from populations that had experienced either random mating or one generation of
      sib-sib inbreeding, we measured the preferences of females for males. Our results
      indicate that outbred males were chosen more often than inbred males and that
      this preference may be more pronounced in outbred females than in inbred ones.

PMID- 29225419
TI  - Colloidal Synthesis of Strongly Fluorescent CsPbBr3 Nanowires with Width Tunable
      down to the Quantum Confinement Regime.

PMID- 29225420
TI  - Projection-based stabilization of interface Lagrange multipliers in
      immersogeometric fluid-thin structure interaction analysis, with application to
      heart valve modeling.
AB  - This paper discusses a method of stabilizing Lagrange multiplier fields used to
      couple thin immersed shell structures and surrounding fluids. The method retains
      essential conservation properties by stabilizing only the portion of the
      constraint orthogonal to a coarse multiplier space. This stabilization can easily
      be applied within iterative methods or semi-implicit time integrators that avoid
      directly solving a saddle point problem for the Lagrange multiplier field. Heart
      valve simulations demonstrate applicability of the proposed method to 3D unsteady
      simulations. An appendix sketches the relation between the proposed method and a
      high-order-accurate approach for simpler model problems.

PMID- 29225421
TI  - Flow-through microfluidic immunosensors with refractive index-matched silica
      monoliths as volumetric optical detection elements.
AB  - A sensitive and rapid absorbance based immunosensor that utilizes ex situ
      functionalized porous silica monoliths as volumetric optical detection elements
      is demonstrated in this study. The porous monolith structure facilitates high
      capture probe density and short diffusion length scales, enabling sensitive and
      rapid assays. Silica monoliths, synthesized and functionalized with immunocapture
      probes off-chip before integration into a sealed thermoplastic microfluidic
      device, serve to capture target antigens during perfusion through the porous
      structure. Gold nanoparticle immunoconjugates are combined with silver
      enhancement to create microscale silver clusters, followed by perfusion of an
      aqueous sucrose solution to limit light scattering and enhance optical signal.
      Using this approach, detection limits as low as 1 ng/mL are achieved for a
      sandwich assay, with a dynamic range of at least 4 logs. The results confirm that
      the combination of on-chip index matching with functionalized porous silica
      monoliths can enables simple and practical flow-through immunoassays for the
      sensitive and rapid detection of target antigens.

PMID- 29225422
TI  - A mangrove creek restoration plan utilizing hydraulic modeling.
AB  - Despite the valuable ecosystem services provided by mangrove ecosystems they
      remain threatened around the globe. Urban development has been a primary cause
      for mangrove destruction and deterioration in south Florida USA for the last
      several decades. As a result, the restoration of mangrove forests has become an
      important topic of research. Using field sampling and remote-sensing we assessed
      the past and present hydrologic conditions of a mangrove creek and its connected
      mangrove forest and brackish marsh systems located on the coast of Naples Bay in
      southwest Florida. We concluded that the hydrology of these connected systems had
      been significantly altered from its natural state due to urban development. We
      propose here a mangrove creek restoration plan that would extend the existing
      creek channel 1.1 km inland through the adjacent mangrove forest and up to an
      adjacent brackish marsh. We then tested the hydrologic implications using a
      hydraulic model of the mangrove creek calibrated with tidal data from Naples Bay
      and water levels measured within the creek. The calibrated model was then used to
      simulate the resulting hydrology of our proposed restoration plan. Simulation
      results showed that the proposed creek extension would restore a twice-daily
      flooding regime to a majority of the adjacent mangrove forest and that there
      would still be minimal tidal influence on the brackish marsh area, keeping its
      salinity at an acceptable level. This study demonstrates the utility of combining
      field data and hydraulic modeling to aid in the design of mangrove restoration
      plans.

PMID- 29225423
TI  - Adiposity Measures and Plasma Adipokines in Females with Rheumatoid and
      Osteoarthritis.
AB  - The objective of this study was to examine the relationship between adipokines
      and adiposity in individuals with rheumatoid and osteoarthritis in the Atlantic
      PATH cohort. Using a nested case-control analysis, participants in the Atlantic
      PATH cohort with rheumatoid or osteoarthritis were matched for measures of
      adiposity with participants without a history of arthritis. Both measured and
      self-reported data were used to examine disease status, adiposity, and lifestyle
      factors. Immunoassays were used to measure plasma markers. BMI was positively
      correlated with percentage body fat, fat mass index (FMI), and a change in BMI
      from 18 years of age in all 3 groups. There were no statistical differences
      between levels of plasma adipokines; adiponectin levels were 6.6, 7.9, and 8.2
      MUg/ml, leptin levels were 10.3, 13.7, and 11.5 ng/ml, and resistin levels were
      10.0, 12.1, and 10.8 ng/ml in participants without arthritis, with rheumatoid
      arthritis, and with osteoarthritis, respectively. Those with higher levels of
      adiponectin were more likely to have osteoarthritis (but not rheumatoid
      arthritis). No association was found between arthritis types and leptin or
      resistin. This study demonstrates differences in measures of adiposity and
      adipokines in specific types of arthritis and highlights the need for more
      research targeting specific adipokines during arthritic disease progression.

PMID- 29225424
TI  - Parametric analysis of electromechanical and fatigue performance of total knee
      replacement bearing with embedded piezoelectric transducers.
AB  - Total knee arthroplasty (TKA) is a common procedure in the United States; it has
      been estimated that about 4 million people are currently living with primary knee
      replacement in this country. Despite huge improvements in material properties,
      implant design, and surgical techniques, some implants fail a few years after
      surgery. A lack of information about in vivo kinetics of the knee prevents the
      establishment of a correlated intra- and postoperative loading pattern in knee
      implants. In this study, a conceptual design of an ultra high molecular weight
      (UHMW) knee bearing with embedded piezoelectric transducers is proposed, which is
      able to measure the reaction forces from knee motion as well as harvest energy to
      power embedded electronics. A simplified geometry consisting of a disk of UHMW
      with a single embedded piezoelectric ceramic is used in this work to study the
      general parametric trends of an instrumented knee bearing. A combined finite
      element and electromechanical modeling framework is employed to investigate the
      fatigue behavior of the instrumented bearing and the electromechanical
      performance of the embedded piezoelectric. The model is validated through
      experimental testing and utilized for further parametric studies. Parametric
      studies consist of the investigation of the effects of several dimensional and
      piezoelectric material parameters on the durability of the bearing and electrical
      output of the transducers. Among all the parameters, it is shown that adding
      large fillet radii results in noticeable improvement in the fatigue life of the
      bearing. Additionally, the design is highly sensitive to the depth of
      piezoelectric pocket. Finally, using PZT-5H piezoceramics, higher voltage and
      slightly enhanced fatigue life is achieved.

PMID- 29225425
TI  - Free Market Ideology and Deregulation in Colorado's Oilfields: Evidence for
      triple movement activism?
AB  - Unconventional oil and gas extraction (UOGE) has spurred an unprecedented boom in
      on-shore production in the U.S. Despite a surge in related research, a void
      exists regarding inquiries into policy outcomes and perceptions. To address this,
      support for federal regulatory exemptions for UOGE is examined using survey data
      collected in 2015 from two northern Colorado communities. Current regulatory
      exemptions for UOGE can be understood as components of broader societal processes
      of neoliberalization. Free market ideology increases public support for federal
      regulatory exemptions for UOGE. Perceived negative impacts do not necessarily
      drive people to support increased federal regulation. Utilizing neo-Polanyian
      theory, interaction between free market ideology and perceived negative impacts
      is explored. Free market ideology appears to moderate people's views of
      regulation: increasing the effect of perceived negative impacts while
      simultaneously increasing support for deregulation. To conclude, the ways in
      which free market ideology might normalize the impacts of UOGE activity are
      discussed.

PMID- 29225426
TI  - Incidence and predictors of total knee arthroplasty following knee arthroscopy.
AB  - Objective: The purpose of this study was to determine the effectiveness of knee
      arthroscopy (KA) in patients with symptomatic meniscal tears or mechanical
      symptoms and OA, by using conversion to TKA as a final outcome measure. Methods:
      Retrospective review of all patients with OA who underwent KA in our practice.
      Results: 1215 KAs were reviewed; 3.9% underwent conversion to TKA at an average
      of 3.2 years. Conclusion: KA plays a role in delaying TKA in knees with meniscal
      tears and mechanical symptoms with concurrent OA.

PMID- 29225427
TI  - Molecular docking analysis of curcumin analogues with COX-2.
AB  - Curcumin analogues were evaluated for COX-2 inhibitory as anti-inflammatory
      activities. The designed analogues significantly enhance COX-2 selectivity. The
      three compounds could dock into the active site of COX-2 successfully. The
      binding energies of -8.2, - 7.6 and -7.5 kcal/mol were obtained for three
      analogues of curcumin respectively. Molecular docking study revealed the binding
      orientations of curcumin analogues in the active sites of COX-2 towards the
      design of potent inhibitors.

PMID- 29225428
TI  - Ymr210wp leads to the accumulation of phospholipids and steryl esters in yeast.
AB  - Ymr210w was identified as a MAG (Monoacylglycerol) lipase. The accumulation of
      the phospholipids in the ymr210wDelta was not clearly understood. It was
      expressed in S. cerevisiae using pYES2/CT vector and His-tag purified recombinant
      protein confirmed TAG lipase activity. To further evaluate the role of YMR210w,
      ester hydrolase activity was also confirmed with pNP-acetate, pNP-butyrate and
      pNP - palmitate. GC-MS lipid profiling of ymr210wDelta showed an increase in the
      15:0 Pentadecanoic acid by 76% among the total lipids. Phospholipid, Erucic acid
      22:1 (Delta13) showed 43% increase while steryl esters showed significant changes
      with 16:0 hexadecanoic acid augmentations by 80% and 18:0 Octadecanoic acid by
      165% when compared to wild type (WT). Increase in the steryl ester and TAG
      content supports the accumulation of lipid bodies in ymr210wDelta strain when
      compared with WT cells.

PMID- 29225429
TI  - In Silico Validation of D7 Salivary Protein-derived B- and T-cell Epitopes of
      Aedes aegypti as Potential Vaccine to Prevent Transmission of Flaviviruses and
      Togaviruses to Humans.
AB  - Mosquito (Aedes aegyptii) salivary proteins play a crucial role in facilitating
      viral transmission from vector-to-host due to their role in facilitating the
      "blood meal" of the vector. Three main proteins, D7, aegyptin and Sialokinin play
      a role in this process. Using in-silico programs, we identified B- and T-cell
      epitopes in the mosquito salivary proteins D7 long and short form. T-cell
      epitopes with high affinity to the most prevalent HLA MHC class-I supertypes
      among different population groups was chosen. It is our postulate that these
      epitopes could be successful in eliciting B and T cell responses, which would
      decrease the vector blood meal efficiency and hence protect against host
      infection by certain viruses. These include causative agents like Dengue viruses,
      Chikungunya virus, Zika and Yellow fever viruses. These viruses are of major
      public health importance in several countries in the Americas, Asia and Africa.
      Experimental evidence exists in previously published literature showing the
      protective effect of antibodies to certain salivary proteins in susceptible
      hosts. A novel approach of immunizing humans against the vector proteins to
      reduce transmission of viruses is now under investigation in several
      laboratories. We have identified the following two B cell epitopes
      LAALHVTAAPLWDAKDPEQF one from D7L and the other TSEYPDRQNQIEELNKLCKN from D7S.
      Likewise, two T cell epitopes MTSKNELDV one from D7L and the other YILCKASAF from
      D7S with affinity to the predominant MHC class-I supertypes were identified
      towards evaluation as potential vaccine.

PMID- 29225430
TI  - Insights from the Molecular dynamics simulation of BcsD Subunit from K. xylinus.
AB  - Biofilms are bacteria living in micro-colonies with a protective coating in
      sessile form. The biofilm protects bacteria from harsh surroundings as well as
      help in antibiotics resistance using a semi-fluid substance. Cellulose is the
      major component of biofilm, which provides the sticky appearance to bacteria for
      attaching to the substratum. The bacteria communicate in biofilm with the help of
      quorum sensing hormones Acylated Homoserine Lactones (AHL's). In Komagataeibacter
      xylinus the four genes Bcs A, Bcs B, Bcs C, Bcs D are associated with cellulose
      biosynthesis. The Bcs D subunits have a hypothetical octamer pore-like structure
      through which glucan molecule pass to form the cellulose. Therefore, it is of
      interest to document a structural understanding of Bcs D. Hence a homology model
      of Bcs D was simulated and analyzed further to gain functional insight towards
      biofilm formation.

PMID- 29225431
TI  - Insights from the protein-protein interaction network analysis of Mycobacterium
      tuberculosis toxin-antitoxin systems.
AB  - Protein-protein interaction (PPI) network analysis is a powerful strategy to
      understand M. tuberculosis (Mtb) system level physiology in the identification of
      hub proteins. In the present study, the PPI network of 79 Mtb toxin-antitoxin
      (TA) systems comprising of 167 nodes and 234 edges was investigated. The
      topological properties of PPI network were examined by 'Network analyzer' a
      cytoscape plugin app and STRING database. The key enriched biological processes
      and the molecular functions of Mtb TA systems were analyzed by STRING. Manual
      curation of the PPI data identified four proteins (i.e. Rv2762c, VapB14, VapB42
      and VapC42) to possess the highest number of interacting partners. The top 15%
      hub proteins were identified in the PPI network by employing two statistical
      measures, i.e. betweenness and radiality by employing cytohubba. Insights gained
      from the molecular protein models of VapC9 and VapC10 are also documented.

PMID- 29225432
TI  - Molecular docking based screening of a simulated HIF-1 protein model for
      potential inhibitors.
AB  - Hypoxia inducible factor-1(HIF-1) is a bHLH-family transcription factor that
      control genes involved in glucolysis, angiogenesis, migration, as well as
      invasion factors that are important for tumor progression and metastasis. HIF-1,
      a hetero dimer of HIF-1alpha and HIF-1beta, binds to the hypoxia responsive
      genes, such as vascular endothelial growth factor (VEGF). It is one the molecular
      target for angiogenesis. A series of Chalcone - like compounds described that
      preferentially inhibit HIF-1 dimer, which can interact with amino acids within
      the active site of the protein. It is of interest model the HIF-1 dimer protein
      and protein was subjected to molecular dynamics simulations using NAMD 2.9
      software with CHARMM27 force field in water and the protein structure was
      minimized with 25000 steps for 500 ps and simulation with 1000000 steps for 2ns.
      2500 compounds were screened from Zinc database through structure based virtual
      screening with references to Chalcone natural drug compound. The screened
      compounds were docked into the active site of the protein using AutoDock Vina in
      PyRx Virtual screening tool. The docking result showed the compounds
      Zinc04280532, Zinc04280533, Zinc04280469, Zinc04280534, Zinc16405915,
      Zinc04277060, Zinc04280538, Zinc04582923, Zinc05280554 and Zinc05943723 have high
      binding affinities then query compound. The lead hit compounds were also testing
      for toxicity and bioavailability using Osiris and Molinspiration online server.
      The active site amino acids such as TYR-21, ASN-34, VAL-35, MET-18, LYS-17, SER
      36, ARG- 46 and ARG-14 are key role in the inhibitors activity. This is useful in
      the design of small molecule therapeutics or the treatment of different
      abnormalities associated with impaired HIF-1alpha.

PMID- 29225433
TI  - Supervoxels for Graph Cuts-Based Deformable Image Registration Using Guided Image
      Filtering.
AB  - In this work we propose to combine a supervoxel-based image representation with
      the concept of graph cuts as an efficient optimization technique for 3D
      deformable image registration. Due to the pixels/voxels-wise graph construction,
      the use of graph cuts in this context has been mainly limited to 2D applications.
      However, our work overcomes some of the previous limitations by posing the
      problem on a graph created by adjacent supervoxels, where the number of nodes in
      the graph is reduced from the number of voxels to the number of supervoxels. We
      demonstrate how a supervoxel image representation, combined with graph cuts-based
      optimization can be applied to 3D data. We further show that the application of a
      relaxed graph representation of the image, followed by guided image filtering
      over the estimated deformation field, allows us to model 'sliding motion'.
      Applying this method to lung image registration, results in highly accurate image
      registration and anatomically plausible estimations of the deformations.
      Evaluation of our method on a publicly available Computed Tomography lung image
      dataset (www.dir-lab.com) leads to the observation that our new approach compares
      very favorably with state-of-the-art in continuous and discrete image
      registration methods achieving Target Registration Error of 1.16mm on average per
      landmark.

PMID- 29225434
TI  - Estimation of Sobolev embedding constant on a domain dividable into bounded
      convex domains.
AB  - This paper is concerned with an explicit value of the embedding constant from
      [Formula: see text] to [Formula: see text] for a domain [Formula: see text]
      ([Formula: see text]), where [Formula: see text]. We previously proposed a
      formula for estimating the embedding constant on bounded and unbounded Lipschitz
      domains by estimating the norm of Stein's extension operator. Although this
      formula can be applied to a domain Omega that can be divided into a finite number
      of Lipschitz domains, there was room for improvement in terms of accuracy. In
      this paper, we report that the accuracy of the embedding constant is
      significantly improved by restricting Omega to a domain dividable into bounded
      convex domains.

PMID- 29225435
TI  - Perspective: Cardiovascular Disease among Young African American Males.

PMID- 29225436
TI  - Perspective: Late-Stage (T4) Translation Research and Implementation Science: The
      National Heart, Lung, and Blood Institute Strategic Vision.
AB  - In August 2016, the National Heart, Lung, and Blood Institute (NHLBI) released
      its Strategic Vision for charting a course for research over the next decade.
      This vision was the culmination of an unprecedented process that engaged diverse
      stakeholders from across the United States and around the globe. The process
      resulted in four mission-oriented goals and eight strategic objectives that
      provide an overall framework for advancing research in heart, lung, and blood
      diseases and sleep disorders. In this perspective, we address opportunities that
      NHLBI has identified to advance late-stage (T4) translation research,
      implementation science, health inequities research, global health research, and
      related research workforce development. Additionally, we highlight the importance
      of continued active engagement of the clinical and public health research
      community and the strategic, transdisciplinary, cross-sector partnerships
      necessary for advancing research priorities to maximize the population-level
      outcomes and health impact of scientific discoveries.

PMID- 29225437
TI  - Inequalities in Hypertension and Diabetes in Canada: Intersections between Racial
      Identity, Gender, and Income.
AB  - A growing body of research from the United States informed by intersectionality
      theory indicates that racial identity, gender, and income are often entwined with
      one another as determinants of health in unexpectedly complex ways. Research of
      this kind from Canada is scarce, however. Using data pooled from ten cycles (2001
      2013) of the Canadian Community Health Survey, we regressed hypertension (HT) and
      diabetes (DM) on income in subsamples of Black women (n = 3,506), White women (n
      = 336,341), Black men (n = 2,806) and White men (n = 271,260). An increase of one
      decile in income was associated with lower odds of hypertension and diabetes
      among White men (ORHT = .98, 95% CI (.97, .99); ORDM = .93, 95% CI (.92, .94))
      and White women (ORHT = .95, 95% CI (.95, .96); ORDM = .90, 95% CI (.89, .91)).
      In contrast, an increase of one decile in income was not associated with either
      health outcome among Black men (ORHT = .99, 95% CI (.92, 1.06); ORDM = .99, 95%
      CI (.91, 1.08)) and strongly associated with both outcomes among Black women
      (ORHT = .86, 95% CI (.80, .92); ORDM = .83, 95% CI (.75, .92)). Our findings
      highlight the complexity of the unequal distribution of hypertension and
      diabetes, which includes inordinately high risks of both outcomes for poor Black
      women and an absence of associations between income and both outcomes for Black
      men in Canada. These results suggest that an intersectionality framework can
      contribute to uncovering health inequalities in Canada.

PMID- 29225438
TI  - Influence of Language and Culture in the Primary Care of Spanish-Speaking Latino
      Adults with Poorly Controlled Diabetes: A Qualitative Study.
AB  - Background: We examined the role of language and culture in the interactions
      between Spanish-speaking Latino patients with poorly controlled diabetes - a fast
      growing population in the United States - and their primary care providers.
      Methods: We conducted four focus groups with 36 non-US born Spanish-speaking
      patients with elevated HbA1c. Participants were insured health plan members with
      either English-speaking (2 groups) or Spanish-speaking (2 groups) primary care
      providers. Moderated discussions focused on visit preparation, communication
      during visit, and role of other care team members. Key themes derived from these
      discussions were then linked to corresponding Latino cultural constructs.
      Results: Patients had a mean age of 57.9 (+/-11.2) years and last measured HbA1c
      was 8.6% (1.5%). Two communication-related themes (reluctance to switch providers
      and use of intermediaries) and two visit-related themes (provider-driven visit
      agendas and problem-based visits) emerged from our analyses. These themes
      reflected the cultural constructs of confianza (trust), familismo (family),
      respeto (deference), and simpatia (harmonious relationship). Trust in the patient
      provider relationship led many participants to remain with English-speaking
      providers who treated them well. Patients with either language concordant and
      discordant providers reported reliance on family or other intermediaries to close
      communication gaps. Deference to physician expertise and authority led to visit
      expectations that it is the doctor's job to know what to ask and that visits were
      intended to address specific, often symptom-driven problems. Conclusions: Spanish
      speaking Latino patients' cultural expectations play an important role in framing
      their primary care interactions. Recognizing culturally influenced visit
      expectations is an important step toward improving patient-provider
      communication.

PMID- 29225439
TI  - Exploring the "Obesity Paradox" as a Correlate of Cognitive and Physical Function
      in Community-dwelling Black and White Older Adults.
AB  - Objective: The obesity paradox has been documented in aged populations, yet it
      remains unclear if this paradox persists for physical and cognitive outcomes in
      community-dwelling older adult populations. Our study examines associations
      between body mass index (BMI) classification, cognitive function, and physical
      function. We also investigate whether these associations are modified by race or
      age. Design: Cross-sectional study. Setting: Senior residential sites and
      community centers in Saint Louis, Missouri. Participants: Study participants
      included 331 adults, aged >55 years. Age was stratified into young-old (aged 55
      74 years) and older (aged >=75 years). Outcome Measures: Physical function was
      measured using the mini-Physical Performance Test (mini-PPT) and grip strength.
      Cognitive function was assessed with the Short Blessed Test (SBT) and the Trail
      Making Tests (TMT-A and TMT-B) performance. Results: Older adults who were obese
      had significantly better cognitive flexibility (TMT-B) performance than normal
      weight older adults (P=.02), and this association was not influenced by age or
      race. Adiposity was not associated with psychomotor speed (TMT-A), general
      cognition (SBT), or measures of physical function (Ps>.05). Conclusion: In a
      diverse sample of community-dwelling older adults, we found partial support for
      the controversial obesity paradox. Our results suggest excess adiposity may be
      protective for executive function processes. Future research is needed to examine
      the underlying physiological processes linking adiposity to executive function in
      older adults.

PMID- 29225440
TI  - Smoking Urges During Treatment and Long-Term Cessation among Low-Income African
      Americans.
AB  - Objective: The urge to smoke is a predictor of smoking relapse. Little research
      has focused on the impact of acute urges during treatment among African
      Americans. This study examined the relationship between smoking urges and long
      term abstinence among treatment seekers. Design: Longitudinal prospective
      investigation. Urges to smoke were assessed at the initial (session 1) and final
      (session 8) sessions among adult smokers (N=308) enrolled in a 4-week group
      intervention trial. Nicotine patch use was assessed over 30 days. Main Outcome
      Measures: Biochemically verified 7-day point prevalence abstinence (7-day ppa)
      was assessed immediately post-intervention, and at 3-, 6-, and 12-month follow
      ups. Hierarchical logistic regressions tested associations between session 1 and
      session 8 urges and 7-day ppa at each smoking status assessment. Results: There
      was a significant overall decrease in smoking urges (M=29, SD=15 at session 1;
      M=17, SD=11 at session 8). After controlling for covariates, urges to smoke at
      session 1 were unrelated to 7-day ppa at any of the assessment points. However,
      session 8 urges were inversely associated with 7-day ppa post-intervention
      (AOR=.94, CI:.92-.97), at 3-months (AOR=.93, CI: .89-.97), 6-months (AOR=.93, CI:
      .90-.97), and 12-months (AOR=.96, CI: .96-.99). Nicotine patch use was positively
      associated with 7-day ppa at each assessment. Conclusions: The most robust
      predictors of abstinence through 12-months post-intervention were decreased urges
      over the 4-week, 8-session group intervention and the frequency of nicotine patch
      use. Interventions aimed at addressing the needs of African American smokers
      should address urges and encourage nicotine replacement adherence to increase
      abstinence rates.

PMID- 29225441
TI  - A Racial Comparison of Differences between Self-Reported and Objectively Measured
      Physical Activity among US Adults with Diabetes.
AB  - Objective: To investigate: 1) the racial/ethnic disparities in meeting the
      recommended physical activity as measured by subjective vs objective measures in
      a national sample of individuals with type 2 diabetes mellitus; and 2) the
      racial/ethnic differences with respect to the magnitude of the discrepancy
      between self-reported and objectively measured moderate-to-vigorous intensity
      aerobic physical activity (MVPA). Methods: We used data from the National Health
      and Nutrition Examination Survey (NHANES) 2003-06 to calculate and compare the
      percentage of individuals with diabetes who achieved the recommended levels of
      physical activity as measured by subjective self-report (500 metabolic
      equivalents (MET)-minutes/week) and objective accelerometer measurement (150
      minutes per week of MVPA) across racial/ethnic groups. Results: 71.2%, 15.7%, and
      13.1% of participants were White, African American, and Hispanic, respectively.
      Based on self-report, 67.1%, 39.2%, and 55.1% of Whites, African Americans, and
      Hispanics, respectively, met the 500 MET-minutes/week threshold of physical
      activity (P<.0001). Objective measurement by accelerometer showed that 44.2%,
      42.6%, and 65.1% of Whites, African Americans, and Hispanics, respectively, met
      the threshold (P<.0003). Conclusions: Many individuals with type 2 diabetes
      mellitus did not meet the recommended physical activity thresholds. African
      Americans had the lowest proportion of meeting both the self-reported and
      objectively measured thresholds. White patients with diabetes overestimated
      frequency of their physical activity, while their Hispanic counterparts
      significantly underestimated it. Also, the gap between the two measures of MVPA
      was largest among Hispanics.

PMID- 29225442
TI  - Increasing Physical Activity in Black Women: Results from a Randomized Trial
      Conducted in Faith-Based Settings.
AB  - Objective: The Learning and Developing Individual Exercise Skills (L.A.D.I.E.S.)
      for a Better Life study compared a faith-integrated (FI) and a secular (SEC)
      intervention for increasing physical activity with a self-guided (SG) control
      group among African American women. Design/Setting/Participants: L.A.D.I.E.S. was
      a cluster randomized, controlled trial. Churches (n=31) were randomized and women
      within each church (n=12 - 15) received the same intervention. Interventions: FI
      and SEC participants received 24 group-based sessions, delivered over 10 months.
      SG participants received printed materials to review independently for 10 months.
      Participants were followed for 12-months post-intervention to assess long-term
      intervention impact. Main Outcome Measures: Data on participant characteristics,
      physical activity, and intervention-related constructs were collected at
      baseline, 10 months, and 22 months. Results: Intervention session attendance was
      greater for FI compared with SEC participants (15.7 + 5.7 vs 12.4 + 7.3 sessions,
      respectively, P<.01). After 10 months, FI and SEC participants significantly
      increased daily walking (+1,451 and +1,107 steps/day, respectively) compared with
      SG participants (-128 steps/day). Increases were maintained after 22 months in
      the FI group compared with the SG group (+1092 vs. +336 daily steps, P<.01).
      Between-group changes in accelerometer-assessed physical activity were not
      statistically significant at any time point. Conclusions: The FI intervention is
      a feasible strategy for short- and long-term increases in physical activity among
      African American women. Additional dissemination and evaluation of the strategy
      could be useful for reducing chronic disease in this high-risk population.

PMID- 29225443
TI  - Perceived Stress in Black and Latino Male Firefighters: Associations with Risk
      and Protective Factors.
AB  - Objective: To compare the prevalence of work-related protective and risk factors
      among Black and Latino male firefighters and to examine the association of these
      factors to perceived stress among both ethnic groups. Design Setting
      Participants: Participants included 1,036 male, career firefighters who self
      identified as Black (n=477) or Latino (n=559) from a large fire department in a
      major metropolitan city in the southwestern United States. As part of a
      department-wide suicide prevention program conducted in 2008, participants
      completed an anonymous and voluntary mental health needs survey. Measures: The
      needs survey included questions regarding prevalence of work-related protective
      and risk factors, the RAPS-4 to assess substance abuse problems, and the 10-item
      Perceived Stress Scale. Results: Results of regression analyses indicated that
      for both Black and Latino male firefighters, alcohol abuse (beta =.13, beta
      =.22), self-reported good health (beta = -.23, beta =-.24) and a positive
      partner/spouse relationship (beta =-.14, beta = -.15) were related to perceived
      stress. In addition, having a second job (beta = .12) and a sense of life calling
      (beta =-.10) were related to perceived stress only among Latino firefighters. All
      associations were in the expected direction as indicated by the signs of the
      standardized beta coefficients (beta). Conclusion: Black and Latino male
      firefighters reported relatively high levels of perceived stress. However, there
      were both differences and similarities in the factors associated to perceived
      stress among the ethnic groups. Therefore, interventions to help firefighters
      reduce or manage stress need to take into account that factors associated with
      perceived stress may vary by ethnic group.

PMID- 29225444
TI  - Prevalence and Correlates of Major Depressive Symptoms among Black Men with
      Prostate Cancer.
AB  - Objectives: The objectives of our study were to determine the prevalence of major
      depressive symptoms and identify factors that are associated with major
      depressive symptoms among Black men with prostate cancer (PCa). Design: This
      study consisted of 415 Black men aged 40-81 years that entered the North Carolina
      Central Cancer Registry during the years 2007-2008. The primary outcome variable
      was depressive symptoms (CES-D). Factors included age, income, education,
      insurance status, treatment received, time between diagnosis and treatment,
      Gleason score, medical mistrust and experience with racism/discrimination.
      Logistic regression models were used to assess factors associated with the odds
      of having major depressive symptoms. Results: The prevalence of major depressive
      symptoms (>=16 on CES-D) among our sample of Black men with PCa was approximately
      33%. Approximately 15% of the study participants underwent radiation beam
      treatment. Age was significantly associated with the odds of reporting major
      depressive symptoms (OR= .95, CI .91-.99) among Black men. In addition, compared
      with all other forms of treatment, Black men who underwent radiation beam
      treatment had higher odds (OR=2.38, CI 1.02- 5.51) of reporting major depressive
      symptoms. Conclusion: Nearly one-third of Black men with PCa in this study
      reported major depressive symptoms. Clinicians should pay closer attention to the
      mental health status of Black men with PCa, especially those who are younger and
      those who have undergone radiation beam treatment. Cancer survivorship,
      particularly quality of life, may be enhanced by opportunities for assessment,
      evaluation and intervention of depressive symptoms among these men
      disproportionately affected by PCa.

PMID- 29225445
TI  - "They have said that I was slightly depressed but there are circumstances that
      bring that on": How Middle-Aged and Older African American Men Describe Perceived
      Stress and Depression.
AB  - Objective: Few studies have focused on how men perceive stress and depression,
      and even fewer have examined how men of a specific racial or ethnic group
      describe their experiences of these conditions. African American men tend to
      define health in ways that are inclusive of their physical health, health
      behaviors, and mental health, but research has largely failed to explore how men
      put their health and mental health in social contexts. The objective of this
      article is to explore how middle-aged and older African American men who self
      identify as having depression: 1) differentiate stress from depression; and 2)
      describe depression. Design: Using data from semi-structured, individual
      interviews conducted between March and April 2014, we used a phenomenological
      approach to examine how men describe, experience, and perceive stress and
      depression. Setting: Nashville, Tennessee. Participants: 18 African American men
      aged 35-76 years who self-reported a previous or current diagnosis of depression.
      Results: Men talked about the experiences of stress and how many of them viewed
      chronic stress as expected and depression as a normal part of life. They used
      phrases like being "slightly depressed" or "I take a light antidepressant" to
      describe how they feel and what they are doing to feel better. Within these
      narratives, men had difficulty distinguishing between stress and depression and
      they primarily explained that depression was the result of external stressors and
      strains. Conclusions: Men may have difficulty distinguishing between stress and
      depression and they may frame the causes of depression in ways that decrease
      their perceived culpability for its causes and limit their perceived control over
      the causes of depression.

PMID- 29225446
TI  - Use of Internet for General and Dental Health along Acculturation Features in a
      Sample of Mexican Americans.
AB  - The objectives of this study were to explore self-reported Internet and
      electronic platforms used to search for and store medical and dental information
      among people of Mexican origin. A sample of adults self-identified as European
      American (250) and as Mexican American (255), residing in Central Indiana,
      answered a one-time survey that included technology use questions and measured
      acculturation via the Psychological-Behavioral Acculturation Scale. Overall use
      of information technologies was estimated through an Information and
      Communication Technology score. Overall, participants with higher scores searched
      online for general and oral health information at higher rates than those with
      lower scores. Younger Mexican Americans and those with higher use scores were
      more likely to search online for general health information, as were those more
      psychologically and behaviorally acculturated. Interestingly, Mexican Americans
      were more likely than European Americans to search online for dental health
      information. All participants demonstrated high interest in accessing and storing
      their own health information especially on paper format; storage in other places,
      such as personal computers, smartphones, or USB flash drives, was less endorsed.
      Most participants would allow spouses access to their health records; however,
      there were significant differences between both population groups regarding
      access given to physicians, dentists and other family members, with Mexican
      Americans reporting more restrictions. Our findings provide initial information
      on differential use pattern of electronic health resources among Mexican
      Americans and suggest that new information technologies reach population groups
      traditionally underserved; such features may help address disparities in general
      and dental health.

PMID- 29225447
TI  - Engaging African Americans in Research: The Recruiter's Perspective.
AB  - Purpose: To examine barriers recruiters encounter when enrolling African American
      study participants, identify motivating factors to increase research
      participation, and provide recommendations to facilitate successful minority
      recruitment. Background: Recruiters are often the first point of contact between
      the research study and potential African American participants. While challenges
      in enrolling African Americans into clinical and epidemiologic research has been
      reported in numerous studies the non-physician recruiter's role as a determinant
      of overall participation rates has received minimal attention. Methods: We
      conducted four 90-minute teleconference focus groups with 18 recruiters
      experienced in enrolling African Americans for clinical and epidemiologic studies
      at five academic/medical institutions. Participants represented diverse racial
      and ethnic backgrounds and were asked to reflect on barriers preventing African
      Americans from participating in research studies, factors that motivated
      participation, and recommendations to increase participation of African Americans
      in research. Multi-coder and thematic data analysis was implemented using the
      Braun and Clarke method. Results: Prominent concerns in recruitment of African
      Americans in research include fear and mistrust and inflexible research
      protocols. The participants suggest that improved recruitment could be achieved
      through cross-cultural and skillset building training opportunities for
      recruiters, greater community engagement among researchers, and better engagement
      with clinic staff and research teams.

PMID- 29225448
TI  - Commentary: De-implementation Science: A Virtuous Cycle of Ceasing and Desisting
      Low-Value Care Before Implementing New High Value Care.
AB  - Implementation science has traditionally focused on increasing the delivery of
      evidence-based care. The science of systematically stopping low-value and
      wasteful care is substantially under-recognized, and if successful, may decrease
      the workload of clinicians. De-implementation science identifies problem areas of
      low-value and wasteful practice, carries out rigorous scientific examination of
      the factors that initiate and maintain such behaviors, and then employs evidence
      based interventions to cease these practices. In this commentary, we describe how
      this approach for de-implementation might require a different set of health
      systems supports, economic and non-economic levers, and behavior change
      techniques that can lead to a virtuous cycle, ie, a complex chain of events that
      positively reinforce themselves through a feedback loop of removing low-value
      care to make room for high quality care.

PMID- 29225449
TI  - Action Centered Contextual Bandits.
AB  - Contextual bandits have become popular as they offer a middle ground between very
      simple approaches based on multi-armed bandits and very complex approaches using
      the full power of reinforcement learning. They have demonstrated success in web
      applications and have a rich body of associated theoretical guarantees. Linear
      models are well understood theoretically and preferred by practitioners because
      they are not only easily interpretable but also simple to implement and debug.
      Furthermore, if the linear model is true, we get very strong performance
      guarantees. Unfortunately, in emerging applications in mobile health, the time
      invariant linear model assumption is untenable. We provide an extension of the
      linear model for contextual bandits that has two parts: baseline reward and
      treatment effect. We allow the former to be complex but keep the latter simple.
      We argue that this model is plausible for mobile health applications. At the same
      time, it leads to algorithms with strong performance guarantees as in the linear
      model setting, while still allowing for complex nonlinear baseline modeling. Our
      theory is supported by experiments on data gathered in a recently concluded
      mobile health study.

PMID- 29225450
TI  - Therapist Use of Specific and Nonspecific Strategies Across Two Affect-Focused
      Psychotherapies for Depression: Role of Adherence Monitoring.
AB  - Psychotherapists routinely use both specific and non-specific strategies to
      deliver empirically supported treatments (ESTs). Psychotherapy adherence
      monitoring has traditionally focused on assessing therapist use of EST-specific
      strategies (to distinguish between ESTs), paying less attention to non-specific
      techniques common to multiple psychotherapies. This study used the Collaborative
      Study Psychotherapy Rating Scale (CSPRS) to evaluate therapist use of both
      specific and non-specific techniques in two affect-focused ESTs for depression.
      Blinded raters evaluated 180 recorded sessions of interpersonal psychotherapy
      (IPT) and brief supportive psychotherapy (BSP). Because IPT and BSP both
      emphasize attention to affective states and developing a warm therapy
      relationship, we expected overlap across scales measuring therapist warmth,
      empathy, and focus on feelings. In contrast, we expected differences in scales
      measuring therapist directiveness, as well as IPT- and BST-specific
      interventions. Results showed raters displayed good inter-rater reliability on
      primary subscales and could discriminate between two treatments with considerable
      overlap. Both IPT and BSP therapists used similarly high levels of non-specific,
      facilitative interventions. Expectedly, IPT therapists were more directive and
      used more IPT-specific strategies, while BSP therapists utilized more non
      directive, supportive strategies. Unexpectedly, BSP therapists showed greater
      focus on feelings than IPT therapists. Exploratory analyses suggested that
      greater focus on feelings in early sessions was associated with greater
      depressive symptom reduction in the first eight weeks of treatment for both ESTs.
      Additional treatment adherence research is needed to investigate both shared and
      distinctive features of ESTs, as well as the effect of the relative use of
      specific versus non-specific interventions on psychotherapy outcomes.

PMID- 29225451
TI  - The Efficacy of a Home-School Intervention for Preschoolers With Challenging
      Behaviors: A Randomized Controlled Trial of Preschool First Step to Success.
AB  - The field of early intervention is currently faced with the challenge of reducing
      the prevalence of antisocial behavior in children. Longitudinal outcomes research
      indicates that increased antisocial behavior and impairments in social competence
      skills during the preschool years often serve as harbingers of future adjustment
      problems in a number of domains including mental health, interpersonal relations,
      and academic achievement. This article reports the results of a cross-site
      randomized controlled trial, in which 128 preschool children with challenging
      behaviors were assigned to either a Preschool First Step to Success (PFS)
      intervention (i.e., experimental) or a usual-care (i.e., control) group.
      Regression analyses indicated that children assigned to the Preschool First Step
      intervention had significantly higher social skills, and significantly fewer
      behavior problems, across a variety of teacher- and parent-reported measures at
      postintervention. Effect sizes for teacher-reported effects ranged from medium to
      large across a variety of social competency indicators; effect sizes for parent
      reported social skills and problem behaviors were small to medium, respectively.
      These results suggest that the preschool adaptation of the First Step
      intervention program provides early intervention participants, staff, and
      professionals with a viable intervention option to address emerging antisocial
      behavior and externalizing behavior disorders prior to school entry.

PMID- 29225452
TI  - The Effects of Perceived Racial/Ethnic Discrimination on Substance Use Among
      Youths Living in the Cherokee Nation.
AB  - We examined frequency and intensity of racial/ethnic discrimination and the
      longitudinal relationship to substance use. The sample included (N = 1,421)
      American Indian, American Indian and White, and White adolescents. A high
      frequency of perceived racial discrimination was associated with an increased
      risk for heavy alcohol use, prescription drug misuse, and other illicit drug use.
      Experiences of perceived racial discrimination high in intensity were associated
      with further increased risk of prescription drug misuse and other illicit drug
      use. Race/ethnicity did not moderate the relationship between perceived racial
      discrimination and substance use. Interventions targeting the deleterious effects
      of racial discrimination may need to be designed to account for both the
      environment and the individual.

PMID- 29225453
TI  - A Comparison of Methods for Uncovering Sample Heterogeneity: Structural Equation
      Model Trees and Finite Mixture Models.
AB  - Although finite mixture models have received considerable attention, particularly
      in the social and behavioral sciences, an alternative method for creating
      homogeneous groups, structural equation model trees (Brandmaier, von Oertzen,
      McArdle, & Lindenberger, 2013), is a recent development that has received much
      less application and consideration. It is our aim to compare and contrast these
      methods for uncovering sample heterogeneity. We illustrate the use of these
      methods with longitudinal reading achievement data collected as part of the Early
      Childhood Longitudinal Study-Kindergarten Cohort. We present the use of
      structural equation model trees as an alternative framework that does not assume
      the classes are latent and uses observed covariates to derive their structure. We
      consider these methods as complementary and discuss their respective strengths
      and limitations for creating homogeneous groups.

PMID- 29225454
TI  - Exploratory Mediation Analysis via Regularization.
AB  - Exploratory mediation analysis refers to a class of methods used to identify a
      set of potential mediators of a process of interest. Despite its exploratory
      nature, conventional approaches are rooted in confirmatory traditions, and as
      such have limitations in exploratory contexts. We propose a two-stage approach
      called exploratory mediation analysis via regularization (XMed) to better address
      these concerns. We demonstrate that this approach is able to correctly identify
      mediators more often than conventional approaches and that its estimates are
      unbiased. Finally, this approach is illustrated through an empirical example
      examining the relationship between college acceptance and enrollment.

PMID- 29225455
TI  - Treatment of Major Depressive Disorder with Iyengar Yoga and Coherent Breathing:
      A Randomized Controlled Dosing Study.
AB  - Objectives: The aims of this study were to assess the effects of an intervention
      of Iyengar yoga and coherent breathing at five breaths per minute on depressive
      symptoms and to determine optimal intervention yoga dosing for future studies in
      individuals with major depressive disorder (MDD). Methods: Subjects were
      randomized to the high-dose group (HDG) or low-dose group (LDG) for a 12-week
      intervention of three or two intervention classes per week, respectively.
      Eligible subjects were 18-64 years old with MDD, had baseline Beck Depression
      Inventory-II (BDI-II) scores >=14, and were either on no antidepressant
      medications or on a stable dose of antidepressants for >=3 months. The
      intervention included 90-min classes plus homework. Outcome measures were BDI-II
      scores and intervention compliance. Results: Fifteen HDG (Mage=38.4+/-15.1 years)
      and 15 LDG (Mage=34.7+/-10.4 years) subjects completed the intervention. BDI-II
      scores at screening and compliance did not differ between groups (p=0.26). BDI-II
      scores declined significantly from screening (24.6+/-1.7) to week 12 (6.0+/-3.8)
      for the HDG (-18.6+/-6.6; p < 0.001), and from screening (27.7+/-2.1) to week 12
      (10.1+/-7.9) in the LDG (-17.7+/-9.3; p < 0.001). There were no significant
      differences between groups, based on response (i.e., >50% decrease in BDI-II
      scores; p=0.65) for the HDG (13/15 subjects) and LDG (11/15 subjects) or
      remission (i.e., number of subjects with BDI-II scores <14; p=1.00) for the HDG
      (14/15 subjects) and LDG (13/15 subjects) after the 12-week intervention,
      although a greater number of subjects in the HDG had 12-week BDI-II scores <=10
      (p=0.04). Conclusion: During this 12-week intervention of yoga plus coherent
      breathing, depressive symptoms declined significantly in patients with MDD in
      both the HDG and LDG. Both groups showed comparable compliance and clinical
      improvements, with more subjects in the HDG exhibiting BDI-II scores <=10 at week
      12.

PMID- 29225456
TI  - Ciliary neurotrophic factor in patients with primary open-angle glaucoma and age
      related cataract.
AB  - Purpose: To study the ciliary neurotrophic factor (CNTF) concentration in the
      aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with
      age-related cataract and primary open-angle glaucoma (POAG). Methods: CNTF
      concentrations were studied in 61 patients with age-related cataract, 55 patients
      with POAG combined with cataract, and 29 healthy controls (one eye in each
      person). Preliminary experiments permitted us to extend the minimum quantifiable
      value of the CNTF Quantikine enzyme-linked immunosorbent assay (ELISA) kit to 2.5
      pg/ml. Results: The levels of CNTF in LF and BS did not differ in patients with
      cataract and controls. The CNTF concentration (pg/ml) in patients with POAG and
      cataract was lower than in patients with cataract (p<0.001) in AH (39.9+/-26.2
      versus 57.2+/-25.6) and in LF (25.7+/-14.9 versus 39.9+/-18.0). The differences
      were not statistically significant for the CNTF level in BS (5.45+/-4.72 versus
      5.96+/-4.92) and the AH/LF ratio (1.69+/-1.05 versus 1.58+/-0.70). In the
      patients with POAG, the AH level of CNTF correlated with the visual field index
      (Pearson's correlation coefficient r = 0.35, p = 0.01). A statistically
      significant decrease in the AH and LF concentrations of CNTF was observed in
      patients in all stages of POAG compared with the cataract group. This decrease
      was particularly prominent in patients with severe glaucoma. Compared to patients
      with combined early and moderate stages of disease patients with advanced
      glaucoma showed an insignificant reduction in the median CNTF concentration in AH
      and LF. The serum CNTF concentration did not show any dependence on the glaucoma
      stage. The CNTF concentration in the AH strongly correlated with the CNTF
      concentration in the LF (r=0.71, p<0.000). A formula was suggested to calculate
      the concentration of CNTF in AH based on the CNTF concentration in LF.
      Conclusions: The CNTF concentration is reduced in the AH and LF of patients with
      POAG, especially in those with severe visual field loss. The CNTF concentration
      in AH and LF showed a strong correlation, and this phenomenon opens up new
      options for a noninvasive estimation of the CNTF concentration in AH. The CNTF
      concentration established in the AH, LF, and BS of patients with age-related
      cataract can serve as normative data for persons older than 50 years old.

PMID- 29225457
TI  - Corneal regeneration by induced human buccal mucosa cultivated on an amniotic
      membrane following alkaline injury.
AB  - : Various clinical disorders and injuries, such as chemical, thermal, or
      mechanical injuries, may lead to corneal loss that results in blindness. PURPOSE:
      The aims of this study were to differentiate human buccal mucosa (BMuc) into
      corneal epithelial-like cells, to fabricate engineered corneal tissue using
      buccal mucosal epithelial cells, and to reconstruct a damaged corneal epithelium
      in a nude rat model. Methods: BMuc were subjected to 10 d of induction factors to
      investigate the potential of cells to differentiate into corneal lineages.
      Results: Corneal stem cell markers beta1-integrin, C/EBPdelta, ABCG2, p63, and
      CK3 were upregulated in the gene expression analysis in induced BMuc, whereas CK3
      and p63 showed significant protein expression in induced BMuc compared to the
      uninduced cells. BMuc were then left to reach 80% confluency after differential
      trypsinization. The cells were harvested and cultivated on a commercially
      available untreated air-dried amniotic membrane (AM) in a Transwell system in
      induction medium. The corneal constructs were fabricated and then implanted into
      damaged rat corneas for up to 8 weeks. A significant improvement was detected in
      the treatment group at 8 weeks post-implantation, as revealed by slit lamp
      biomicroscopy analysis. The structure and thickness of the corneal layer were
      also analyzed using histological staining and time-domain optical coherence
      tomography scans and were found to resemble a native corneal layer. The protein
      expression for CK3 and p63 were continuously detected throughout the corneal
      epithelial layer in the corneal construct. Conclusions: In conclusion, human BMuc
      can be induced to express a corneal epithelial-like phenotype. The addition of
      BMuc improves corneal clarity, prevents vascularization, increases corneal
      thickness and stromal alignment, and appears to have no adverse effect on the
      host after implantation.

PMID- 29225458
TI  - Antiangiogenic effect of dasatinib in murine models of oxygen-induced retinopathy
      and laser-induced choroidal neovascularization.
AB  - Purpose: Vascular endothelial growth factor (VEGF) is a principal mediator of
      pathological ocular neovascularization, which is the leading cause of blindness
      in various ocular diseases. As Src, a non-receptor tyrosine kinase, has been
      implicated as one of the major signaling molecules in VEGF-mediated
      neovascularization, the present study aimed to investigate whether dasatinib, a
      potent Src kinase inhibitor, could suppress pathological ocular
      neovascularization in murine models of oxygen-induced retinopathy (OIR) and
      choroidal neovascularization (CNV). Methods: Tube formation, scratch wounding
      migration, and cell proliferation assays were performed to measure the inhibitory
      effect of dasatinib on VEGF-induced angiogenesis in human retinal microvascular
      endothelial cells. Murine models of OIR and laser-induced CNV were used to assess
      the preventive effect of an intravitreal injection of dasatinib on pathological
      neovascularization in the retina and choroid. Neovascularization and Src
      phosphorylation were evaluated with immunofluorescence staining. Results:
      Dasatinib efficiently inhibited VEGF-induced endothelial proliferation, wounding
      migration, and tube formation. In mice with OIR and laser injury-induced CNV,
      eyes treated with a single intravitreal injection of dasatinib exhibited
      significant decreases in pathological neovascularization compared with that of
      controls injected with vehicle. The dasatinib-treated OIR mice also showed a
      decrease in Src phosphorylation in the periretinal tufts. The intravitreal
      injection of dasatinib did not cause ocular toxicity at the treatment dose
      administered. Conclusions: These results demonstrated that dasatinib suppressed
      pathological neovascularization in the mouse retina and choroid. Therefore,
      dasatinib may be indicated for the treatment of ischemia-induced proliferative
      retinopathy and neovascular age-related macular degeneration.

PMID- 29225459
TI  - Research into Theory into Practice: An Overview of Family Based Interventions for
      Child Antisocial Behavior Developed at the Oregon Social Learning Center.
AB  - Although many psychotherapeutic approaches exist for treating troubled children
      and their families, not all have been evaluated to be effective through research.
      Moreover, among those that have been determined to be "evidence-based," few have
      followed as coherent and rigorous a path of rigorous scientific investigation as
      the interventions that have been developed at the Oregon Social Learning Center.
      As such, these interventions serve as a model of "research to theory to practice"
      that may not only be employed to support families with children in need of
      treatment, but may also guide other programs of treatment development. This is
      the story of how this work has unfolded over the past four decades.

PMID- 29225460
TI  - Intravitreal bevacizumab injections versus dexamethasone implant for treatment
      naive retinal vein occlusion related macular edema.
AB  - Purpose: To compare the short-term effects of three monthly intravitreal
      bevacizumab (IVB) injections to single dexamethasone (DEX) implantation in
      treatment-naive patients with cystoid macular edema (CME) secondary to branch
      (BRVO) and central retinal vein occlusion (CRVO). Design: A retrospective single
      center study. Subjects: A total of 135 eyes of 135 patients with BRVO (n=83) and
      CRVO (n=52). Methods: Changes in clinical parameters were recorded before
      treatment and at the first and third month after commencement of IVB (n=121) and
      DEX (n=14). Main outcome measures: Central retinal thickness (CRT), intraocular
      pressure (IOP), and best-corrected visual acuity (BCVA). Results: The baseline
      parameters were comparable between IVB and DEX groups. After the first month, CRT
      decreased by 131.3+/-42.9 MUm in IVB and by 266.9+/-48.3 MUm in DEX (mean +/-
      SEM; p=0.047). IOP change was -0.29+/-0.39 mmHg in IVB and +3.70+/-2.34 mmHg in
      DEX (p=0.005). IOP elevation to >=25 mmHg and >=5 mmHg from the baseline was
      observed in two of the DEX- and in none of the IVB-treated eyes (p=0.010). After
      the third month, no differences regarding CRT and IOP were observed between the
      treatment modalities. Moreover, BCVA gain was comparable between IVB (0.37+/-0.05
      logarithm of minimum angle of resolution [logMAR] units) and DEX (0.33+/-0.30
      logMAR units) groups. Conclusion: DEX was associated with faster resolution of
      CME, but had greater probability for short-term IOP elevation when compared to
      IVB. After the third month, treatments were comparably effective. Anatomical
      outcomes and adverse drug reactions of IVB versus DEX should be considered case
      specifically in patients having CME secondary to BRVO/CRVO.

PMID- 29225461
TI  - Risperidone mucoadhesive buccal tablets: formulation design, optimization and
      evaluation.
AB  - The aim of this study was to design and optimize risperidone (RIS) mucoadhesive
      buccal tablets for systemic delivery as an alternative route. Direct compression
      method was used for the preparation of buccal tablets, and screening studies were
      conducted with different polymers to determine their effects on tablet
      characteristics. Carbopol(r) (CP) and sodium alginate (SA) were selected as two
      polymer types for further optimization studies by applying response surface
      methodology. Tablet hardness (TH), ex vivo residence time (RT), and peak
      detachment force (DF) from buccal mucosa were selected as three important
      responses. Physicochemical compatibility of formulation excipients and RIS was
      evaluated by using Fourier transform infrared (FT-IR) spectroscopy and
      differential scanning calorimetry (DSC) analysis. In vitro drug release profiles
      and release kinetics were investigated; swelling index and matrix erosion studies
      were conducted. Optimum formulation consisted of 16.4% CP and 20.3% SA, which
      provided 7.67+/-0.29 hour ex vivo RT, 45.52+/-4.85 N TH, and 2.12+/-0.17 N DF. FT
      IR spectroscopy and DSC analysis revealed that there was no chemical interaction
      present between tablet ingredients. Cumulative RIS release of >90% was achieved
      after 8 hours of in vitro dissolution studies, which was supported by swelling
      and matrix erosion analysis. Mechanism of RIS release was fitted best to zero
      order model, while release exponent (n) value of 0.77 demonstrated an anomalous
      (non-Fickian) release, indicating combined erosion and swelling mechanism. The
      results suggested that optimized buccal tablets of RIS would be a promising and
      alternative delivery system for the treatment of schizophrenia.

PMID- 29225462
TI  - The increase in health care costs associated with muscle weakness in older people
      without long-term illnesses in the Czech Republic: results from the Survey of
      Health, Ageing and Retirement in Europe (SHARE).
AB  - Muscle weakness and associated diseases are likely to place a considerable
      economic burden on government health care expenditure. Therefore, our aim for
      this study was to estimate the direct and indirect costs associated with muscle
      weakness in the Czech Republic. We applied a cost-of-illness approach using data
      from the Survey of Health, Ageing and Retirement in Europe (SHARE). Six hundred
      and eighty-nine participants aged 70 years and over and without any long-term
      illnesses were included in our study. A generalized linear model with gamma
      distribution was used, and odds ratio (OR) was calculated in order to explore the
      effect of muscle weakness on direct and indirect costs. For both genders, muscle
      weakness had a statistically significant impact on direct costs (OR =2.11), but
      did not have a statistically significant impact on indirect costs (OR =1.08) or
      on total cost (OR =1.51). Muscle weakness had the greatest statistically
      significant impact on direct costs in females (OR =2.75). In conclusion, our
      study has shown that muscle weakness may lead to increased direct costs, and
      consequently place a burden on health care expenditure. Therefore, the results of
      this study could lead to greater interest in the prevention of muscle weakness
      among older people in the Czech Republic.

PMID- 29225463
TI  - Nano-copper-bearing stainless steel promotes fracture healing by accelerating the
      callus evolution process.
AB  - Treatment for fractures requires internal fixation devices, which are mainly
      produced from stainless steel or titanium alloy without biological functions.
      Therefore, we developed a novel nano-copper-bearing stainless steel with nano
      sized copper-precipitation (317L-Cu SS). Based on previous studies, this work
      explores the effect of 317L-Cu SS on fracture healing; that is, proliferation,
      osteogenic differentiation, osteogenesis-related gene expression, and lysyl
      oxidase activity of human bone mesenchymal stem cells were detected in vitro.
      Sprague-Dawley rats were used to build an animal fracture model, and fracture
      healing and callus evolution were investigated by radiology (X-ray and micro-CT),
      histology (H&E, Masson, and safranin O/fast green staining), and
      histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were
      determined, and local mechanical test of the fracture was performed to assess the
      healing quality. Our results revealed that 317L-Cu SS did not affect the
      proliferation of human bone mesenchymal stem cells, but promoted osteogenic
      differentiation and the expression of osteogenesis-related genes. In addition,
      317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results
      showed that the callus evolution efficiency and fracture healing speed were
      superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous
      tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further,
      histomorphometric analysis indicated that the callus possessed higher osteogenic
      efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression
      were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of
      the fracture site was much better than that of the control group. Overall, we
      conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and
      promote osteogenesis in the callus, which could accelerate the callus evolution
      process and bone formation to provide faster and better fracture healing.

PMID- 29225464
TI  - Apolipoprotein E3-mediated cellular uptake of reconstituted high-density
      lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles.
AB  - We have developed a high-density lipoprotein (HDL)-based platform for transport
      and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of
      apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density
      lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into
      glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two
      synthesized by phase transfer process, were solubilized by integration with
      phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs.
      Ultraviolet-visible spectra of rHDL-AuNP indicated the presence of stable
      particles with surface plasmon band at ~530 nm. Transmission electron microscopy
      (TEM) of rHDL-AuNP revealed roughly spherical particles with AuNPs embedded in
      the core. The rHDL-AuNP particles displayed robust binding to the LDLr and were
      internalized by receptor-mediated endocytosis in glioblastoma cells. Confocal
      microscopy confirmed cellular uptake of AuNPs in the endosomal-lysosomal
      compartments, while TEM revealed intracellular aggregated AuNPs. Cell viability
      assay demonstrated that >85% of cells were viable with rHDL-AuNP treatment of 0.1
      100 MUg/mL for 24 hours. These findings are significant since they offer an
      effective means of delivering AuNPs across the cell membrane, which is
      particularly relevant in tumor cells that overexpress LDLr.

PMID- 29225465
TI  - The effect of errorless learning on quality of life in patients with Korsakoff's
      syndrome.
AB  - Background: Errorless learning (EL) is a promising rehabilitation principle for
      (re)learning instrumental activities in patients with amnesia, including patients
      with Korsakoff's syndrome (KS). Successfully (re)learning tasks might improve the
      sense of competence and independence, and subsequently the quality of life.
      Quality of life in patients with KS has received limited attention, and no
      studies have been conducted to experimentally examine the effect of EL on quality
      of life in patients in this patient group. Materials and methods: The QUALIDEM,
      an observation scale for quality of life, was completed by professional nurses
      before and after EL training in a group of fifty-one patients with KS. This scale
      was also completed for a group of thirty-one control patients receiving care as
      usual but no EL training. Results: Quality of life was significantly increased on
      eight of the nine subscales in the Korsakoff group who participated in an EL
      training. There was a trend toward a significant increase in "positive affect"
      (ie, the ninth subscale). In contrast, no changes over time were found on any of
      the subscales in the control group that did not participate in any EL training.
      Conclusion: Despite severe memory impairments, patients with KS still have the
      potential to (partially) (re)learn tasks using EL. This potential should be
      exploited, as the successes of (re)-learning might improve the quality of life of
      Korsakoff patients in nursing homes.

PMID- 29225467
TI  - Altered emotional recognition and expression in patients with Parkinson's
      disease.
AB  - Background: Parkinson's disease (PD) patients exhibit deficits in emotional
      recognition and expression abilities, including emotional faces and voices. The
      aim of this study was to explore emotional processing in pre-deep brain
      stimulation (pre-DBS) PD patients using two sensory modalities (visual and
      auditory). Methods: Fifteen PD patients who needed DBS surgery and 15 healthy,
      age- and gender-matched controls were recruited as participants. All participants
      were assessed by the Karolinska Directed Emotional Faces database 50 Faces
      Recognition test. Vocal recognition was evaluated by the Montreal Affective
      Voices database 50 Voices Recognition test. For emotional facial expression, the
      participants were asked to imitate five basic emotions (neutral, happiness,
      anger, fear, and sadness). The subjects were required to express nonverbal
      vocalizations of the five basic emotions. Fifteen Chinese native speakers were
      recruited as decoders. We recorded the accuracy of the responses, reaction time,
      and confidence level. Results: For emotional recognition and expression, the PD
      group scored lower on both facial and vocal emotional processing than did the
      healthy control group. There were significant differences between the two groups
      in both reaction time and confidence level. A significant relationship was also
      found between emotional recognition and emotional expression when considering all
      participants between the two groups together. Conclusion: The PD group exhibited
      poorer performance on both the recognition and expression tasks. Facial emotion
      deficits and vocal emotion abnormalities were associated with each other. In
      addition, our data allow us to speculate that emotional recognition and
      expression may share a common system.

PMID- 29225468
TI  - Therapy of an incomplete spinal cord injury by intrathecal injection of EPO and
      subcutaneous injection of EPO, vitamin C and G-CSF.
AB  - Spinal cord injury is a rare disease with an incidence about 40 cases per million
      population in the USA. The most common reasons are traffic accidents, falls,
      violence and sports. A 53-year-old male patient presented with an incomplete
      tetraparesis as a result of a spinal cord injury after the accident. It was not
      possible to treat him with steroids because he was out of the therapeutic time
      period of 8 hours when he presented to the hospital. The main problem of spinal
      cord injuries is the secondary injury caused by inflammation and swelling of the
      spinal cord. To avoid this, the patient was experimentally treated with
      erythropoietin (EPO) intrathecal and EPO, granulocyte-colony-stimulating factor
      and vitamin C subcutaneous after his initial spinal cord relief surgery. These
      drugs might be able to relieve this secondary reaction but were never applied for
      this indication in human before. This study shows that it could be a promising
      treatment for spinal cord injuries with potential therapeutic benefits.

PMID- 29225466
TI  - Korsakoff's syndrome: a critical review.
AB  - In this review, we present a survey on Korsakoff's syndrome (KS), a residual
      syndrome in patients who suffered from a Wernicke encephalopathy (WE) that is
      predominantly characterized by global amnesia, and in more severe cases also by
      cognitive and behavioral dysfunction. We describe the history of KS and its
      definition, its epidemiology, and the lack of consensus criteria for its
      diagnosis. The cognitive and behavioral symptoms of KS, which include anterograde
      and retrograde amnesia, executive dysfunction, confabulation, apathy, as well as
      affective and social-cognitive impairments, are discussed. Moreover, recent
      insights into the underlying neurocognitive mechanisms of these symptoms are
      presented. In addition, the evidence so far on the etiology of KS is examined,
      highlighting the role of thiamine and alcohol and discussing the continuity
      hypothesis. Furthermore, the neuropathology of KS is reviewed, focusing on
      abnormalities in the diencephalon, including the mammillary bodies and thalamic
      nuclei. Pharmacological treatment options and nonpharmacological interventions,
      such as those based on cognitive rehabilitation, are discussed. Our review shows
      that thiamine deficiency (TD) is a crucial factor in the etiology of KS. Although
      alcohol abuse is by far the most important context in which TD occurs, there is
      no convincing evidence for an essential contribution of ethanol neurotoxicity
      (EN) to the development of WE or to the progression of WE to KS. Future research
      on the postmortem histopathological analysis of brain tissues of KS patients is
      crucial for the advancement of our knowledge of KS, especially for associating
      its symptoms with lesions in various thalamic nuclei. A necessary requirement for
      the advancement of studies on KS is the broad acceptance of a comprehensive
      definition and definite diagnostic criteria. Therefore, in this review, we
      propose such a definition of KS and draft outlines for prospective diagnostic
      criteria.

PMID- 29225470
TI  - Plasma Cholinesterase Levels of Nepalese Farmers Following Exposure to
      Organophosphate Pesticides.
AB  - Background: Farmers in developing countries use highly toxic organophosphate
      pesticides. Thus, the aim of this study was to compare plasma cholinesterase
      (PChE) enzyme activity before and after exposure to organophosphate pesticides in
      a real-life setting. Methods: This was a prospective study conducted on 25
      farmers spraying organophosphate pesticide in their farm. The PChE level was
      measured and clinical signs and symptoms of toxicity were asked before and
      immediately after spraying. Results: The mean level of PChE before and after
      spraying was 1.41 and 1.29 IU/L, respectively (8.51% decreased). Farmers reported
      more clinical signs and symptoms of intoxication after spraying pesticides.
      Conclusions: Increase in acute intoxication signs/symptoms and decrease in PChE
      indicate a serious public health problem among farmers who use organophosphate
      pesticides. Appropriate training to the farmers is needed to reduce exposure to
      organophosphate pesticide.

PMID- 29225469
TI  - Pelvic vein incompetence: clinical perspectives.
AB  - Chronic pelvic pain (CPP) affects 24% of premenopausal women, accounts for 20%
      30% of UK gynecology outpatient appointments, and has an annual pan-European
      economic cost of ?3.8 billion. Despite extensive investigation, often including
      laparoscopy, up to 55% of women do not receive a diagnosis and endure persistent
      symptoms. In these patients, clinical management focuses on symptom control
      rather than treatment. It is possible that pelvic vein incompetence (PVI) is a
      cause of CPP, although the quality of studies investigating an association is
      generally low. PVI may develop during and after pregnancy, as uterine blood flow
      increases significantly, pushing venous valve leaflets apart, and enabling
      retrograde venous flow. Analogies with varicose veins of the lower limb are
      helpful, and symptoms are similar. Women with symptomatic PVI report a dull
      pelvic ache that is worse on standing and sitting and persists throughout the
      day. It can be relieved by lying down. Early treatments for PVI included
      laparoscopic ligation; however, since the advent of endovascular occlusive
      techniques, treatments have lower risk and lower cost, and can be undertaken
      without sedation or anesthetic. However, there have been no high-quality
      randomized controlled trials of interventions and, therefore, the evidence is
      limited to single-center case series.

PMID- 29225471
TI  - Glucose Tolerance Testing and Anthropometric Comparisons Among Rural Residents of
      Kyiv Region: Investigating the Possible Effect of Childhood Starvation-A
      Community-Based Study.
AB  - A relationship between childhood starvation and type 2 diabetes mellitus (T2D) in
      adulthood was previously indicated. Ukraine suffered a series of artificial
      famines between 1921 and 1947. Famines of 1932 to 1933 and 1946 were most severe
      among them. Long-term health consequences of these famines remain insufficiently
      investigated. Type 2 diabetes mellitus screening was conducted between June 2013
      and December 2014. A total of 198 rural residents of Kyiv region more than 44
      years of age, not registered as patients with T2D, were randomly selected. In
      all, 159 persons answered the question about starvation of parental family,
      including 73 born before 1947. Among them, 62 persons answered positive.
      Anthropometric measurements and glucose tolerance tests were performed. A
      logistic regression model was used to evaluate results. Type 2 diabetes mellitus
      was detected in 7 of 62 persons (11.3%), who starved during childhood vs 6 of 11
      (54.5%) who did not (P = .002), age-adjusted and sex-adjusted odds ratio (OR)
      (95% confidence interval): 0.063 (0.007-0.557). Analysis of the anthropometric
      data revealed a negative connection between adulthood height and neck
      circumference (cm, continued variables) and childhood starvation: age-adjusted
      and sex-adjusted ORs 0.86 (0.76-0.97) and 0.73 (0.54-0.97), respectively.
      Individuals who starved during famines of 1932 to 1933 and 1946 in Ukraine had a
      decreased T2D prevalence several decades after the famine episodes.

PMID- 29225472
TI  - 18F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma.
AB  - Objective: MET is a member of the receptor tyrosine kinases. Several MET
      targeting inhibitors and antagonistic antibodies have shown promising data in
      clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to
      estimate the status of MET is helpful in clinical practice. 18F
      fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG
      PET/CT) has been used routinely for the diagnosis and staging of tumors. However,
      the relationship between MET expression and 18F-FDG uptake has not been
      investigated yet. This study aimed to determine the correlation of MET expression
      with 18F-FDG uptake on PET-CT scan and whether or not 18F-FDG PET/CT can be used
      to predict the MET status of lung adenocarcinoma patients. Patients and methods:
      Fifty-seven lung adenocarcinoma patients were analyzed in our study. Maximum
      standardized uptake value (SUVmax) was calculated in all PET/CT images. The
      expression levels of MET and two important glycolysis-related markers, glucose
      transporter 1 (GLUT1) and pyruvate kinase M2, were analyzed by
      immunohistochemistry of tissues. Spearman rank correlation was used to analyze
      the association between MET expression and SUVmax. In vitro MET knockdown in lung
      adenocarcinoma cells was used to examine the role of MET in tumor metabolism. The
      effect of MET on GLUT1 expression was investigated using Western blot assay and
      quantitative polymerase chain reaction. Results: SUVmax was positively correlated
      with the expression levels of MET (r=0.458; P<0.001) and GLUT1 (r=0.551;
      P<0.001). SUVmax was significantly higher in patients with positive MET
      expression than in those with negative MET expression (9.92+/-6.62 vs 4.60+/
      3.00; P=0.002). MET knockdown in lung adenocarcinoma cells led to a significant
      decrease in GLUT1 expression and 18F-FDG uptake. Conclusion: MET could increase
      18F-FDG uptake by upregulating GLUT1 expression. 18F-FDG PET/CT could be used to
      predict the MET status of lung adenocarcinoma patients and to supply valuable
      information to guide targeted therapy.

PMID- 29225473
TI  - The combination therapy of salinomycin and gefitinib using poly(d,l-lactic-co
      glycolic acid)-poly(ethylene glycol) nanoparticles for targeting both lung cancer
      stem cells and cancer cells.
AB  - Purpose: Lung cancer (LC) is the leading cause of cancer death worldwide.
      Evidences suggest that both LC cancer stem cells (CSCs) and cancer cells are
      supposed to be eliminated to achieve superior treatment effect against LC.
      Salinomycin could eradiate CSCs in various types of cancers, and gefitinib is a
      first-line therapy in LC. The purpose of the present study was to develop
      salinomycin-loaded nanoparticles (salinomycin-NPs) combined with gefitinib-loaded
      nanoparticles (gefitinib-NPs) to eradicate both LC CSCs and cancer cells.
      Methods: Salinomycin and gefitinib were encapsulated separately by poly(d,l
      lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles by the
      emulsion/solvent evaporation approach. The anti-LC activity of salinomycin-NPs
      and gefitinib-NPs was investigated. Results: Salinomycin-NPs and gefitinib-NPs
      are of ~140 nm in size, high drug encapsulation efficacy and sustained release of
      drugs. CD133+ LC CSCs showed the characteristics of CSCs, including significantly
      enhanced stem cell gene expression, tumorsphere formation ability, and
      tumorigenicity in mice. Both salinomycin and salinomycin-NPs are capable of
      selectively inhibiting LC CSCs, as reflected by their enhanced cytotoxic effects
      toward CD133+ LC CSCs and ability to reduce tumorsphere formation in LC cell
      lines, whereas gefitinib and gefitinib-NPs could significantly inhibit LC cells.
      Salinomycin-NPs and salinomycin could reduce the population of LC CSCs in the
      tumors in vivo. It is noteworthy that salinomycin-NPs combined with gefitinib-NPs
      inhibited the growth of tumors more efficiently compared with salinomycin
      combined with gefitinib or single salinomycin-NPs or gefitinib-NPs. Conclusion:
      Salinomycin-NPs combined with gefitinib-NPs represent a potential approach for LC
      by inhibiting both LC CSCs and cancer cells.

PMID- 29225474
TI  - The combination of systemic therapy and locoregional radiotherapy prolongs
      survival in newly diagnosed metastatic nasopharyngeal carcinoma patients.
AB  - Background: The purpose of this study is to assess the role of locoregional
      radiotherapy (RT) when used in combination with systemic chemotherapy, for
      patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), in a non
      endemic region of northern China. Methods: In total, 611 patients with NPCs were
      newly diagnosed between June 2011 and June 2016 following visits to our hospital;
      of these, 32 patients presented with metastasis at initial diagnosis. Among these
      32 patients, 29 had single-organ metastasis and 3 had multiple-organ metastasis.
      All patients were treated with RT for local and regional disease. Results: The
      median follow-up for all patients was 20 months (range 9-59 months), and median
      survival was not achieved (some patients had succumbed) at the time of the last
      follow-up. The 2-year overall survival (OS) rate was 75.2%, and 3-year OS rate
      was 50.1%. There was a significant difference between patients with single- and
      multiple-organ metastasis: 2-year OS was 67.5% for single- vs 0% for multiple
      organ metastasis (p=0.039). Patients treated with intensity-modulated RT had a
      better prognosis than patients treated by conventional RT: 2-year OS was 76.6%
      for single- vs 44.4% for multiple-organ metastasis (no significant difference was
      found between the 2 groups, p=0.297). For patients with progression (all were
      with distant disease progression), the median progression time was 8 months (6-22
      months), and the median survival after disease progression was 6 months (2-14
      months). Conclusion: For patients with newly diagnosed metastatic NPCs,
      especially with single-organ metastasis, the addition of RT to systemic
      chemotherapy improved survival and disease control compared with historical
      cohort.

PMID- 29225475
TI  - PBX3 is associated with proliferation and poor prognosis in patients with
      cervical cancer.
AB  - Pre-B-cell leukemia homeobox 3 (PBX3) is upregulated in various malignancies;
      however, the role of PBX3 in cervical cancer (CC) is unknown. The purpose of this
      study was to explore the expression characteristics, clinicopathological
      significance, and molecular biological function of PBX3 in CC. The expression
      levels of PBX3 were analyzed in CC cell lines and tumor specimens by real-time
      polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical
      staining. The clinicopathological characteristics associated with PBX3 expression
      were evaluated. An RNA interference approach was employed to suppress PBX3
      expression in CC in vitro and in vivo, determine its role in cell proliferation
      and analyze its molecular function. We found that PBX3 expression was
      significantly upregulated in CC cell lines and clinical specimens compared with
      normal cells and adjacent nontumorous cervical tissues. PBX3 was an independent
      predictive factor of poor prognosis, and its expression was correlated with tumor
      diameter, pathological grading, lymph node metastasis, invasion depth, vascular
      invasion, and clinical stage of CC. Multivariate analysis suggested that PBX3
      expression may represent an independent prognostic indicator of the survival of
      CC patients. CC patients with high PBX3 expression exhibited reduced overall
      survival compared with those with low PBX3 expression. Additionally, stable
      downregulation of PBX3 expression in CC cell lines suppressed cell proliferation
      and decreased p-AKT protein expression levels in vitro. Similarly, in vivo assays
      demonstrated that PBX3 downregulation in CC cells markedly inhibited tumor size
      and weight. Overall, we demonstrated that PBX3 can promote CC cell proliferation
      via the AKT signaling pathway and that it may serve as a prognostic marker. Our
      data indicate that inactivation of PBX3 may be an effective clinical treatment
      for CC.

PMID- 29225476
TI  - Association between the IL-6 gene polymorphism and tuberculosis risk: a meta
      analysis.
AB  - Background: The gene polymorphism of interleukin-6 (IL-6) has been shown to be
      implicated in tuberculosis susceptibility in many studies, but with conflicting
      results. This study aimed to provide more accurate estimation of the relationship
      between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis.
      Method: A literature search was performed in PubMed, EMBASE, and other databases.
      Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated.
      Statistical analyses were performed by using STATA 12.0. Results: Twelve
      publications with 2635 cases and 3049 controls were included. The pooled analysis
      demonstrated significant evidence of association between IL-6 (-174G/C) and low
      risk of tuberculosis in dominant model (CC+GC vs GG: OR =0.693, 95% CI 0.581
      0.826, p<0.001). Subgroup analysis got similar results for IL-6 (-174G/C) in
      Asians and Latinos, but the significance did not exist in Caucasians. IL-6 (
      572C/G) polymorphism was also associated with low risk of tuberculosis in
      dominant model (CC+GC vs GG: OR =0.719, 95% CI 0.577-0.896, p=0.003). No
      publication bias was detected in either of the polymorphisms. Conclusion: In
      summary, IL-6 -572 C/G polymorphism may be associated with a decreased risk of
      tuberculosis, and C allele is the protective factor against tuberculosis for IL-6
      -174G/C among Asians and Latinos, but not in Caucasian population.

PMID- 29225477
TI  - Molecular evaluation of colistin-resistant gene expression changes in
      Acinetobacter baumannii with real-time polymerase chain reaction.
AB  - Background: Acinetobacter baumannii is an important human pathogen which has
      recently gained increased attention due to the occurrence of drug-resistant
      nosocomial infections in patients suffering from immune system disorders, and
      those in hospital intensive care units. The aim of this research was to identify
      and isolate A. baumannii strains resistant to colistin, determine antibiotic
      resistance pattern of this bacteria, investigate the presence of colistin
      resistant genes, and finally assess the effect of expression changes in pmrA and
      pmrB genes resistant to A. baumannii against colistin via real-time polymerase
      chain reaction. Methods: The samples were initially purified and isolated using
      biochemical tests and Micro-gen kit. Later, the resistance pattern evaluation of
      validated samples to different antibiotics and colistin was carried out using two
      methods viz., disc diffusion and E-test. This was followed by the assessment of
      genes resistant to colistin via polymerase chain reaction besides gene expression
      changes via real-time polymerase chain reaction. Results: The results of this
      study indicated that eleven strains of A. baumannii isolated from Shahid Rajaee
      Trauma Hospital were resistant to colistin. However, in the resistance pattern
      evaluation of A. baumannii isolated from Ali Asghar Hospital, all the strains
      were sensitive to colistin. In the evaluation of genes resistant to pmrA and
      pmrB, most of the strains resistant to colistin were carriers of these genes.
      Besides, in the expression assessment of these genes, it was demonstrated that
      expression of pmrA in the strains resistant to colistin significantly increased
      in relation to sensitive strains, but the expression of pmrB increased at a lower
      rate in the strains resistant to colistin as compared to the sensitive strains.
      Conclusion: Thus, it can be safely mentioned that increased expression of pmrA
      was due to the resistance of A. baumannii to colistin.

PMID- 29225478
TI  - The utility of biomarkers in hepatocellular carcinoma: review of urine-based 1H
      NMR studies - what the clinician needs to know.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy, the third
      most common cause of cancer death, and the most common primary liver cancer.
      Overall, there is a need for more reliable biomarkers for HCC, as those currently
      available lack sensitivity and specificity. For example, the current gold
      standard biomarker, serum alpha-fetoprotein, has a sensitivity of roughly only
      70%. Cancer cells have different characteristic metabolic signatures in
      biofluids, compared to healthy cells; therefore, metabolite analysis in blood or
      urine should lead to the detection of suitable candidates for the detection of
      HCC. With the advent of metabonomics, this has increased the potential for new
      biomarker discovery. In this article, we look at approaches used to identify
      biomarkers of HCC using proton nuclear magnetic resonance (1H-NMR) spectroscopy
      of urine samples. The various multivariate statistical analysis techniques used
      are explained, and the process of biomarker identification is discussed, with a
      view to simplifying the knowledge base for the average clinician.

PMID- 29225479
TI  - Density of CD8+ lymphocytes in biopsy samples combined with the circulating
      lymphocyte ratio predicts pathologic complete response to chemoradiotherapy for
      rectal cancer.
AB  - Objectives: The systemic status and local immune status, as determined by the
      neutrophil-lymphocyte ratio (NLR) or the lymphocyte ratio (LYMR) and tumor
      infiltrating lymphocyte (TIL) count, respectively, have been suggested as
      predictors of the tumor response to neoadjuvant chemoradiotherapy (nCRT) in
      rectal cancer, although the utility of these measures remains controversial. We
      aimed to investigate the values of the LYMR, NLR and TIL count and their
      combinations (TIL-LYMR/TIL-NLR) in predicting pathologic complete response (pCR)
      after nCRT. Patients and methods: Pretreatment biopsy samples and data from the
      blood tests of 92 patients with rectal cancer who underwent curative resection
      after nCRT were retrospectively obtained. CD8+ TILs were immunostained using an
      antibody against CD8. The density of CD8+ TILs was recorded as the number of CD8+
      T cells per square millimeter, and the results were classified as either "high"
      or "low". The LYMR and NLR were calculated using pretreatment blood test data and
      categorized into either "high" or "low" groups. TIL-LYMR was graded as "low,"
      "mid" or "high" when neither, one or both the CD8+ TIL count and LYMR were
      "high," respectively. TIL-NLR was graded similarly. The associations between TILs
      and LYMR, NLR and their combinations (TIL-LYMR/TIL-NLR) were evaluated. Results:
      pCR was significantly associated with a high LYMR, a low NLR and increased
      chemotherapy cycles (P=0.039, P=0.043 and P=0.015, respectively), but not with
      the CD8+ TIL count or carcinoembryonic antigen (CEA) level (P=0.100 and P=0.590,
      respectively). Additionally, 40% of patients with high LYMR and 40.7% with low
      NLR achieved pCR, whereas only 19.7% with low LYMR and 20.3% with high NLR did
      so. When the combinations were assessed, TIL-LYMR showed a positive correlation
      with pCR (P=0.038), while no association between TIL-NLR and pCR was found
      (P=0.916). In multivariate analysis, TIL-LYMR remained an independent predictor
      of pCR (odds ratio [OR]=1.833, 95% confidence interval [CI]=1.069-3.142,
      P=0.028). Conclusion: High LYMR, low NLR and high TIL-LYMR at baseline are
      predictive of pCR to nCRT for patients with rectal cancer. These parameters may
      help identify pCR patients and provide additional information for therapeutic
      decision-making.

PMID- 29225480
TI  - Role of afatinib in the treatment of advanced lung squamous cell carcinoma.
AB  - Lung cancer treatment has considerably changed over the last few years: the
      identification of druggable oncogenic alterations and innovative immunotherapic
      approaches granted lung cancer patients the possibility of more efficient and
      less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell
      carcinomas (SqCCs) patients have the chance to benefit from novel treatment
      alternatives, including immune checkpoint blockade and anti-angiogenic agents
      and, given positive trial results, from afatinib, a second generation tyrosine
      kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase
      receptors. Considering the role of the ErbB-signaling cascade in lung SqCC, it is
      relevant to note that ErbB1 (epidermal growth factor receptor [EGFR]) is
      overexpressed in 85% of non-small-cell lung carcinomas (NSCLCs), particularly in
      patients with squamous histology, and is associated with poor prognosis. For this
      reason, EGFR activity has been investigated as a therapeutic strategy in lung
      SqCC. Even taking into account statistically positive trial results, anti-EGFR
      approach still remains controversial in unselected/wild-type EGFR lung SqCC
      patients, as well as the optimal timing and sequencing of all available targeted
      therapies considering the approval of immunotherapeutic agents. This review
      analyzes current data about EGFR inhibition in lung SqCC with a specific focus on
      afatinib in order to elucidate available clinical evidence supporting EGFR
      targeting in this setting as well as a future management of advanced lung SqCCs
      in the context of new emerging immunotherapeutic drugs.

PMID- 29225481
TI  - Perspectives on high-intensity interval exercise for health promotion in children
      and adolescents.
AB  - Physical activity lowers future cardiovascular disease (CVD) risk; however, few
      children and adolescents achieve the recommended minimum amount of daily
      activity. Accordingly, there is virtue in identifying the efficacy of small
      volumes of high-intensity exercise for health benefits in children and
      adolescents for the primary prevention of CVD risk. The purpose of this narrative
      review is to provide a novel overview of the available literature concerning high
      intensity interval-exercise (HIIE) interventions in children and adolescents.
      Specifically, the following areas are addressed: 1) outlining the health benefits
      observed following a single bout of HIIE, 2) reviewing the role of HIIE training
      in the management of pediatric obesity, and 3) discussing the effectiveness of
      school-based HIIE training. In total, 39 HIIE intervention studies were included
      in this review. Based upon the available data, a single bout of high-intensity
      exercise provides a potent stimulus for favorable, acute changes across a range
      of cardiometabolic outcomes that are often superior to a comparative bout of
      moderate-intensity exercise (14 studies reviewed). HIIE also promotes
      improvements in cardiorespiratory fitness and cardiometabolic health status in
      overweight and obese children and adolescents (10 studies reviewed) and when
      delivered in the school setting (15 studies reviewed). We thus conclude that high
      intensity exercise is a feasible and potent method of improving a range of
      cardiometabolic outcomes in children and adolescents. However, further work is
      needed to optimize the delivery of HIIE interventions in terms of participant
      enjoyment and acceptability, to include a wider range of health outcomes, and to
      control for important confounding variables (eg, changes in diet and habitual
      physical activity). Finally, research into the application of HIIE training
      interventions to children and adolescents of different ages, sexes, pubertal
      status, and sociocultural backgrounds is required.

PMID- 29225482
TI  - The relationship between empathy and burnout - lessons for paramedics: a scoping
      review.
AB  - Background: The concepts of empathy and burnout are critical for practicing
      paramedics and the profession. While there has been an increasing body of
      research on the relationship between empathy and burnout with physicians and
      nurses, surprisingly, no research has been undertaken with paramedics. The aim of
      this scoping review was to explore the relationship between empathy and burnout.
      Method: A scoping review was performed based on Arskey and O'Malley's framework.
      Five databases were searched: CINAHL plus, EMBASE, MEDLINE, PsycINFO, and Scopus.
      Google Scholar was searched for gray literature. Two reviewers independently
      assessed eligibility and extracted the data. Results: The initial search produced
      a yield of 1270 articles after removal of duplicates. All abstracts were screened
      for relevance, and 30 articles were selected for further screening. Twenty six
      articles were deemed relevant, of which there were 23 cross-sectional studies,
      two editorials, and one description article on the multidimensional aspect of
      burnout and empathy. The studies were conducted in Europe, USA, North America,
      and Asia. In most studies, there was an inverse correlation between empathy and
      emotional exhaustion and depersonalization but a positive correlation with
      personal accomplishment. Conclusion: Although there seems to be a real
      relationship between empathy and burnout in physicians and nurses, the strength
      of the relationship differs to some extent depending on the samples and settings.
      Due to similarities between health professions, the relationship between empathy
      and burnout may also be relevant to the paramedic profession. Future paramedic
      research should focus on longitudinal studies to determine the factors that might
      influence empathy and burnout levels to provide a better understanding of these
      two key factors.

PMID- 29225483
TI  - Active Stromal Cell-Derived Factor 1alpha and Endothelial Progenitor Cells are
      Equally Increased by Alogliptin in Good and Poor Diabetes Control.
AB  - Background: It is postulated that the ability of dipeptidyl peptidase-4
      inhibitors (DPP-4-i) to increase circulating endothelial progenitor cells (EPCs)
      may be at least partly mediated by active stromal cell-derived factor 1alpha (SDF
      1alpha) (a pivotal mediator of stem cell mobilization from the bone marrow). As
      other DPP-4-i were demonstrated to increase EPC concentrations, in this study, we
      sought to investigate the ability of the DPP-4-i alogliptin in modifying EPCs and
      SDF-1alpha, in patients with good and poor diabetes control. Methods: Two groups
      of diabetic patients on metformin were divided by hemoglobin A1c (HbA1c): Group A
      those with HbA1c <=6.5% (28 patients) and Group B-those with HbA1c 7.5% to 8.5%
      (31 patients). Both groups received alogliptin 25 mg/daily for 4 months. At
      baseline and 4 months later, clinical, laboratory parameters, EPCs, and active
      SDF-1alpha were determined. Results: After 4-month treatment with alogliptin,
      either Group A or Group B showed reduced HbA1c levels and concomitant similar
      increase in EPCs and active SDF-1alpha. Conclusions: Alogliptin showed
      significant benefits in increasing EPCs and active SDF-1alpha either in good or
      poor diabetes control. The study demonstrated that similar to other DPP-4-i, also
      alogliptin is able to increase EPC concentrations, suggesting the existence of a
      class effect mediated by SDF-1alpha. The extent of increase in EPCs is
      independent from baseline diabetes control.

PMID- 29225484
TI  - The Prevalence of Iron Deficiency Anemia and its Associated Risk Factors Among a
      Sample of Female University Students in Tabuk, Saudi Arabia.
AB  - Background: Prior data on iron deficiency anemia's (IDA) prevalence and
      associated risk factors among female university students are scarce in the Saudi
      Arabian context. This study therefore recruited a sample of female students at
      the University of Tabuk, Saudi Arabia, to investigate IDA prevalence and risk
      factors and fill the identified research gap. Methods: A cross-sectional study of
      200 apparently healthy female students aged between 19 and 25 years was performed
      between February and June 2016. Data on the participants' sociodemographics,
      diet, health, anthropometry, and hematological and biochemical iron status
      indices were gathered. A logistic regression analysis then revealed the IDA risk
      factors. Results: The IDA prevalence was 12.5%. The factors associated via
      logistic regression with an elevated anemia risk were inadequate iron and vitamin
      C intakes, infrequent (<=2 times per week) consumption of red meat, frequent (>=2
      times per week) tea consumption, and a past personal history of IDA. Conclusions:
      The findings suggest that focused education and awareness strategies are needed
      to improve nutritional habits by encouraging the consumption of rich dietary iron
      sources and by raising awareness of the food and drinks which facilitate or
      hinder the bioavailability of iron.

PMID- 29225485
TI  - Patterns and correlates of co-occurrence among multiple types of child
      maltreatment.
AB  - This study examined the patterns and correlates of the types of maltreatment
      experienced by adolescents aged 9-12, participating in an ongoing longitudinal
      study on the impact of neglect on children's development. Using case record
      abstraction, the study compared the child protection classification and findings
      from the case record abstraction with regard to the rates of four types of
      maltreatment (i.e. physical, sexual, emotional abuse and neglect) as well as co
      occurrence across multiple types of maltreatment. Next, the study examined the
      frequently observed patterns of child maltreatment. Finally, the study
      investigated whether aspects of caretaker functioning and the detailed incident
      characteristics in the cases of neglect differed by the number of different types
      of maltreatment the children experienced. Results showed significant
      discrepancies between the Child Protective Service classification and case record
      abstraction. Child Protective Service classification considerably underestimated
      the rate of co-occurrence across multiple types of maltreatment. Neglect
      accompanied by physical and emotional abuse was the most common form. Some of the
      caretaker functioning variables distinguished the number of types of
      maltreatment. Based on the findings, future-research directions and practice
      implication were discussed.

PMID- 29225487
TI  - An instability of the standard model of cosmology creates the anomalous
      acceleration without dark energy.
AB  - We identify the condition for smoothness at the centre of spherically symmetric
      solutions of Einstein's original equations without the cosmological constant or
      dark energy. We use this to derive a universal phase portrait which describes
      general, smooth, spherically symmetric solutions near the centre of symmetry when
      the pressure p=0. In this phase portrait, the critical k=0 Friedmann space-time
      appears as a saddle rest point which is unstable to spherical perturbations. This
      raises the question as to whether the Friedmann space-time is observable by
      redshift versus luminosity measurements looking outwards from any point. The
      unstable manifold of the saddle rest point corresponding to Friedmann describes
      the evolution of local uniformly expanding space-times whose accelerations
      closely mimic the effects of dark energy. A unique simple wave perturbation from
      the radiation epoch is shown to trigger the instability, match the accelerations
      of dark energy up to second order and distinguish the theory from dark energy at
      third order. In this sense, anomalous accelerations are not only consistent with
      Einstein's original theory of general relativity, but are a prediction of it
      without the cosmological constant or dark energy.

PMID- 29225488
TI  - Ducks in space: from nonlinear absolute instability to noise-sustained structures
      in a pattern-forming system.
AB  - A subcritical pattern-forming system with nonlinear advection in a bounded domain
      is recast as a slow-fast system in space and studied using a combination of
      geometric singular perturbation theory and numerical continuation. Two types of
      solutions describing the possible location of stationary fronts are identified,
      whose origin is traced to the onset of convective and absolute instability when
      the system is unbounded. The former are present only for non-zero upstream
      boundary conditions and provide a quantitative understanding of noise-sustained
      structures in systems of this type. The latter correspond to the onset of a
      global mode and are present even with zero upstream boundary conditions. The role
      of canard trajectories in the nonlinear transition between these states is
      clarified and the stability properties of the resulting spatial structures are
      determined. Front location in the convective regime is highly sensitive to the
      upstream boundary condition, and its dependence on this boundary condition is
      studied using a combination of numerical continuation and Monte Carlo simulations
      of the partial differential equation. Statistical properties of the system
      subjected to random or stochastic boundary conditions at the inlet are
      interpreted using the deterministic slow-fast spatial dynamical system.

PMID- 29225486
TI  - Desmoplastic Small Round Blue Cell Tumor: A Review of Treatment and Potential
      Therapeutic Genomic Alterations.
AB  - Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with
      multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal
      translocation. Ewing sarcoma and DSRCT are treated similarly due to similar
      oncogene activation pathways, and DSRCT has been represented in very limited
      numbers in sarcoma studies. Despite aggressive therapy, median survival ranges
      from 17 to 25 months, and 5-year survival rates remain around 15%, with higher
      survival reported among those undergoing removal of at least 90% of tumor in the
      absence of extraperitoneal metastasis. Almost 100% of these tumors contain
      t(11;22) (p13;q12) translocation, and it is likely that EWS-WT1 functions as a
      transcription factor possibly through WT1 targets. While there is no standard
      protocol for this aggressive disease, treatment usually includes the neoadjuvant
      HD P6 regimen (high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV)
      alternating with ifosfamide and etoposide (IE) chemotherapy combined with
      aggressively attempted R0 resection). We aimed to review the molecular
      characteristics of DSRCTs to explore therapeutic opportunities for this extremely
      rare and aggressive cancer type.

PMID- 29225489
TI  - On stochastic differential equations with arbitrarily slow convergence rates for
      strong approximation in two space dimensions.
AB  - In a recent article (Jentzen et al. 2016 Commun. Math. Sci.14, 1477-1500
      (doi:10.4310/CMS.2016.v14.n6.a1)), it has been established that, for every
      arbitrarily slow convergence speed and every natural number d?{4,5,...}, there
      exist d-dimensional stochastic differential equations with infinitely often
      differentiable and globally bounded coefficients such that no approximation
      method based on finitely many observations of the driving Brownian motion can
      converge in absolute mean to the solution faster than the given speed of
      convergence. In this paper, we strengthen the above result by proving that this
      slow convergence phenomenon also arises in two (d=2) and three (d=3) space
      dimensions.

PMID- 29225490
TI  - Fluid flow in porous media using image-based modelling to parametrize Richards'
      equation.
AB  - The parameters in Richards' equation are usually calculated from experimentally
      measured values of the soil-water characteristic curve and saturated hydraulic
      conductivity. The complex pore structures that often occur in porous media
      complicate such parametrization due to hysteresis between wetting and drying and
      the effects of tortuosity. Rather than estimate the parameters in Richards'
      equation from these indirect measurements, image-based modelling is used to
      investigate the relationship between the pore structure and the parameters. A
      three-dimensional, X-ray computed tomography image stack of a soil sample with
      voxel resolution of 6 MUm has been used to create a computational mesh. The Cahn
      Hilliard-Stokes equations for two-fluid flow, in this case water and air, were
      applied to this mesh and solved using the finite-element method in COMSOL
      Multiphysics. The upscaled parameters in Richards' equation are then obtained via
      homogenization. The effect on the soil-water retention curve due to three
      different contact angles, 0 degrees , 20 degrees  and 60 degrees , was also
      investigated. The results show that the pore structure affects the properties of
      the flow on the large scale, and different contact angles can change the
      parameters for Richards' equation.

PMID- 29225491
TI  - Three-dimensional quasi-periodic shifted Green function throughout the spectrum,
      including Wood anomalies.
AB  - This work, part II in a series, presents an efficient method for evaluation of
      wave scattering by doubly periodic diffraction gratings at or near what are
      commonly called 'Wood anomaly frequencies'. At these frequencies, there is a
      grazing Rayleigh wave, and the quasi-periodic Green function ceases to exist. We
      present a modification of the Green function by adding two types of terms to its
      lattice sum. The first type are transversely shifted Green functions with
      coefficients that annihilate the growth in the original lattice sum and yield
      algebraic convergence. The second type are quasi-periodic plane wave solutions of
      the Helmholtz equation which reinstate certain necessary grazing modes without
      leading to blow-up at Wood anomalies. Using the new quasi-periodic Green
      function, we establish, for the first time, that the Dirichlet problem of
      scattering by a smooth doubly periodic scattering surface at a Wood frequency is
      uniquely solvable. We also present an efficient high-order numerical method based
      on this new Green function for scattering by doubly periodic surfaces at and
      around Wood frequencies. We believe this is the first solver able to handle Wood
      frequencies for doubly periodic scattering problems in three dimensions. We
      demonstrate the method by applying it to acoustic scattering.

PMID- 29225492
TI  - Geometric description of a discrete power function associated with the sixth
      Painleve equation.
AB  - In this paper, we consider the discrete power function associated with the sixth
      Painleve equation. This function is a special solution of the so-called cross
      ratio equation with a similarity constraint. We show in this paper that this
      system is embedded in a cubic lattice with [Formula: see text] symmetry. By
      constructing the action of [Formula: see text] as a subgroup of [Formula: see
      text], i.e. the symmetry group of PVI, we show how to relate [Formula: see text]
      to the symmetry group of the lattice. Moreover, by using translations in
      [Formula: see text], we explain the odd-even structure appearing in previously
      known explicit formulae in terms of the tau function.

PMID- 29225493
TI  - A post Gurney quantum mechanical perspective on the electrolysis of water: ion
      neutralization in solution.
AB  - Electron fluxes crossing the interface between a metallic conductor and an
      aqueous environment are important in many fields; hydrogen production,
      environmental scanning tunnelling microscopy, scanning electrochemical microscopy
      being some of them. Gurney (Gurney 1931 Proc. R. Soc. Lond.134, 137
      (doi:10.1098/rspa.1931.0187)) provided in 1931 a scheme for tunnelling during
      electrolysis and outlined conditions for it to occur. We measure the low-voltage
      current flows between gold electrodes in pure water and use the time-dependent
      behaviour at voltage switch-on and switch-off to evaluate the relative
      contribution to the steady current arising from tunnelling of electrons between
      the electrodes and ions in solution and from the neutralization of ions adsorbed
      onto the electrode surface. We ascribe the larger current contribution to quantum
      tunnelling of electrons to and from ions in solution near the electrodes. We
      refine Gurney's barrier scheme to include solvated electron states and quantify
      energy differences using updated information. We show that Gurney's conditions
      would prevent the current flow at low voltages we observe but outline how the
      ideas of Marcus (Marcus 1956 J. Chem. Phys.24, 966-978 (doi:10.1063/1.1742723))
      concerning solvation fluctuations enable the condition to be relaxed. We derive
      an average barrier tunnelling model and a multiple pathways tunnelling model and
      compare predictions with measurements of the steady-state current-voltage
      relation. The tunnelling barrier was found to be wide and low in agreement with
      other experimental studies. Applications as a biosensing mechanism are discussed
      that exploit the fast tunnelling pathways along molecules in solution.

PMID- 29225494
TI  - Rolling resistance of shallow granular deformation.
AB  - Experiments are conducted to measure the resistance experienced by light
      cylinders rolling over flat beds of granular media. Sand and glass spheres are
      used for the beds. The trajectories of the rolling cylinders are determined
      through optical tracking, and velocity and acceleration data are inferred through
      fits to these trajectories. The rolling resistance is dominated by a velocity
      independent component, but a velocity-dependent drag exceeding the expected
      strength of air drag is also observed. The results are compared to a theoretical
      model based on a cohesionless Mohr-Coulomb rheology for a granular medium in the
      presence of gravity. The model idealizes the flow pattern underneath the rolling
      cylinder as a plastically deforming zone in front of a rigidly rotating plug
      attached to the cylinder, as proposed previously for cylinders rolling on
      perfectly cohesive plastic media. The leading-order, rate-independent rolling
      resistance observed experimentally is well reproduced by the model predictions.

PMID- 29225495
TI  - Force direction patterns promote whole body stability even in hip-flexed walking,
      but not upper body stability in human upright walking.
AB  - Directing the ground reaction forces to a focal point above the centre of mass of
      the whole body promotes whole body stability in human and animal gaits similar to
      a physical pendulum. Here we show that this is the case in human hip-flexed
      walking as well. For all upper body orientations (upright, 25 degrees , 50
      degrees , maximum), the focal point was well above the centre of mass of the
      whole body, suggesting its general relevance for walking. Deviations of the
      forces' lines of action from the focal point increased with upper body
      inclination from 25 to 43 mm root mean square deviation (RMSD). With respect to
      the upper body in upright gait, the resulting force also passed near a focal
      point (17 mm RMSD between the net forces' lines of action and focal point), but
      this point was 18 cm below its centre of mass. While this behaviour mimics an
      unstable inverted pendulum, it leads to resulting torques of alternating sign in
      accordance with periodic upper body motion and probably provides for low
      metabolic cost of upright gait by keeping hip torques small. Stabilization of the
      upper body is a consequence of other mechanisms, e.g. hip reflexes or muscle
      preflexes.

PMID- 29225496
TI  - Age distribution dynamics with stochastic jumps in mortality.
AB  - While deterministic age distribution models have been extensively studied and
      applied in various disciplines, little work has been devoted to understanding the
      role of stochasticity in birth and mortality terms. In this paper, we analyse a
      stochastic M'Kendrick-von Foerster equation in which jumps in mortality represent
      intense losses of population due to external events. We present explicit
      solutions for the probability density functions of the age distribution and the
      total population and for the temporal dynamics of their moments. We also derive
      the dynamics of the mean age of the population and its harmonic mean. The
      framework is then used to calculate the age distribution of salt in the soil root
      zone, where the accumulation of salt by atmospheric deposition is counteracted by
      plant uptake and by jump losses due to percolation events.

PMID- 29225497
TI  - Swelling-induced wrinkling in layered gel beams.
AB  - Gels are widely employed in smart mechanical devices and biomedical applications.
      Swelling-induced bending actuation can be obtained by means of a simple bilayer
      gel beam. We show that this system can also exhibit wrinkling patterns of
      potential interest for structural morphing and sensing. We study swelling-induced
      wrinkling at the extrados of a bilayer gel beam with the softer layer on top. The
      bent configuration at finite strain is recovered first and, starting from it, a
      linear perturbation analysis is performed. We delimit the zone corresponding to
      wrinkling modes in a parameter plane encompassing a mechanical stiffness ratio
      and a geometric top layer to total height ratio. Interestingly, we observe that
      surface instability precedes and envelopes wrinkling modes of finite wavelength.
      Finally, we discuss the effect of changes in stiffness and of the Flory-Huggins
      parameters chi on the size of the wrinkling domain.

PMID- 29225498
TI  - On the buckling of an elastic holey column.
AB  - We report the results of a numerical and theoretical study of buckling in elastic
      columns containing a line of holes. Buckling is a common failure mode of elastic
      columns under compression, found over scales ranging from metres in buildings and
      aircraft to tens of nanometers in DNA. This failure usually occurs through
      lateral buckling, described for slender columns by Euler's theory. When the
      column is perforated with a regular line of holes, a new buckling mode arises, in
      which adjacent holes collapse in orthogonal directions. In this paper, we firstly
      elucidate how this alternate hole buckling mode coexists and interacts with
      classical Euler buckling modes, using finite-element numerical calculations with
      bifurcation tracking. We show how the preferred buckling mode is selected by the
      geometry, and discuss the roles of localized (hole-scale) and global (column
      scale) buckling. Secondly, we develop a novel predictive model for the buckling
      of columns perforated with large holes. This model is derived without arbitrary
      fitting parameters, and quantitatively predicts the critical strain for buckling.
      We extend the model to sheets perforated with a regular array of circular holes
      and use it to provide quantitative predictions of their buckling.

PMID- 29225499
TI  - Analysing causal structures with entropy.
AB  - A central question for causal inference is to decide whether a set of
      correlations fits a given causal structure. In general, this decision problem is
      computationally infeasible and hence several approaches have emerged that look
      for certificates of compatibility. Here, we review several such approaches based
      on entropy. We bring together the key aspects of these entropic techniques with
      unified terminology, filling several gaps and establishing new connections, all
      illustrated with examples. We consider cases where unobserved causes are
      classical, quantum and post-quantum, and discuss what entropic analyses tell us
      about the difference. This difference has applications to quantum cryptography,
      where it can be crucial to eliminate the possibility of classical causes. We
      discuss the achievements and limitations of the entropic approach in comparison
      to other techniques and point out the main open problems.

PMID- 29225500
TI  - Multi-scale mechanics of granular solids from grain-resolved X-ray measurements.
AB  - This work discusses an experimental technique for studying the mechanics of three
      dimensional (3D) granular solids. The approach combines 3D X-ray diffraction and
      X-ray computed tomography to measure grain-resolved strains, kinematics and
      contact fabric in the bulk of a granular solid, from which continuum strains,
      grain stresses, interparticle forces and coarse-grained elasto-plastic moduli can
      be determined. We demonstrate the experimental approach and analysis of selected
      results on a sample of 1099 stiff, frictional grains undergoing multiple uniaxial
      compression cycles. We investigate the inter-particle force network, elasto
      plastic moduli and associated length scales, reversibility of mechanical
      responses during cyclic loading, the statistics of microscopic responses and
      microstructure-property relationships. This work serves to highlight both the
      fundamental insight into granular mechanics that is furnished by combined X-ray
      measurements and describes future directions in the field of granular materials
      that can be pursued with such approaches.

PMID- 29225501
TI  - The grasshopper problem.
AB  - We introduce and physically motivate the following problem in geometric
      combinatorics, originally inspired by analysing Bell inequalities. A grasshopper
      lands at a random point on a planar lawn of area 1. It then jumps once, a fixed
      distance d, in a random direction. What shape should the lawn be to maximize the
      chance that the grasshopper remains on the lawn after jumping? We show that,
      perhaps surprisingly, a disc-shaped lawn is not optimal for any d>0. We
      investigate further by introducing a spin model whose ground state corresponds to
      the solution of a discrete version of the grasshopper problem. Simulated
      annealing and parallel tempering searches are consistent with the hypothesis
      that, for d<pi-1/2, the optimal lawn resembles a cogwheel with n cogs, where the
      integer n is close to [Formula: see text]. We find transitions to other shapes
      for [Formula: see text].

PMID- 29225502
TI  - On the analysis of the double Hopf bifurcation in machining processes via centre
      manifold reduction.
AB  - The single-degree-of-freedom model of orthogonal cutting is investigated to study
      machine tool vibrations in the vicinity of a double Hopf bifurcation point.
      Centre manifold reduction and normal form calculations are performed to
      investigate the long-term dynamics of the cutting process. The normal form of the
      four-dimensional centre subsystem is derived analytically, and the possible
      topologies in the infinite-dimensional phase space of the system are revealed. It
      is shown that bistable parameter regions exist where unstable periodic and, in
      certain cases, unstable quasi-periodic motions coexist with the equilibrium.
      Taking into account the non-smoothness caused by loss of contact between the tool
      and the workpiece, the boundary of the bistable region is also derived
      analytically. The results are verified by numerical continuation. The possibility
      of (transient) chaotic motions in the global non-smooth dynamics is shown.

PMID- 29225503
TI  - Advection and Taylor-Aris dispersion in rivulet flow.
AB  - Motivated by the need for a better understanding of the transport of solutes in
      microfluidic flows with free surfaces, the advection and dispersion of a passive
      solute in steady unidirectional flow of a thin uniform rivulet on an inclined
      planar substrate driven by gravity and/or a uniform longitudinal surface shear
      stress are analysed. Firstly, we describe the short-time advection of both an
      initially semi-infinite and an initially finite slug of solute of uniform
      concentration. Secondly, we describe the long-time Taylor-Aris dispersion of an
      initially finite slug of solute. In particular, we obtain the general expression
      for the effective diffusivity for Taylor-Aris dispersion in such a rivulet, and
      discuss in detail its different interpretations in the special case of a rivulet
      on a vertical substrate.

PMID- 29225504
TI  - Symmetric rearrangement of groundwater-fed streams.
AB  - Streams shape landscapes through headward growth and lateral migration. When
      these streams are primarily fed by groundwater, recent work suggests that their
      tips advance to maximize the symmetry of the local Laplacian field associated
      with groundwater flow. We explore the extent to which such forcing is responsible
      for the lateral migration of streams by studying two features of groundwater-fed
      streams in Bristol, Florida: their confluence angle near junctions and their
      curvature. First, we find that, while streams asymptotically form a 72 degrees 
      angle near their tips, they simultaneously exhibit a wide 120 degrees  confluence
      angle within approximately 10 m of their junctions. We show that this wide angle
      maximizes the symmetry of the groundwater field near the junction. Second, we
      argue that streams migrate laterally within valleys and present a new spectral
      analysis method to relate planform curvature to the surrounding groundwater
      field. Our results suggest that streams migrate laterally in response to fluxes
      from the surrounding groundwater table, providing evidence of a new mechanism
      that complements Laplacian growth at their tips.

PMID- 29225505
TI  - Lagrangian averaging with geodesic mean.
AB  - This paper revisits the derivation of the Lagrangian averaged Euler (LAE), or
      Euler-alpha equations in the light of an intrinsic definition of the averaged
      flow map as the geodesic mean on the volume-preserving diffeomorphism group.
      Under the additional assumption that first-order fluctuations are statistically
      isotropic and transported by the mean flow as a vector field, averaging of the
      kinetic energy Lagrangian of an ideal fluid yields the LAE Lagrangian. The
      derivation presented here assumes a Euclidean spatial domain without boundaries.

PMID- 29225506
TI  - Nonlinear mode interaction in equal-leg angle struts susceptible to cellular
      buckling.
AB  - A variational model that describes the interactive buckling of a thin-walled
      equal-leg angle strut under pure axial compression is presented. A formulation
      combining the Rayleigh-Ritz method and continuous displacement functions is used
      to derive a system of differential and integral equilibrium equations for the
      structural component. Solving the equations using numerical continuation reveals
      progressive cellular buckling (or snaking) arising from the nonlinear interaction
      between the weak-axis flexural buckling mode and the strong-axis flexural
      torsional buckling mode for the first time-the resulting behaviour being highly
      unstable. Physical experiments conducted on 10 cold-formed steel specimens are
      presented and the results show good agreement with the variational model.

PMID- 29225507
TI  - How to characterize a nonlinear elastic material? A review on nonlinear
      constitutive parameters in isotropic finite elasticity.
AB  - The mechanical response of a homogeneous isotropic linearly elastic material can
      be fully characterized by two physical constants, the Young's modulus and the
      Poisson's ratio, which can be derived by simple tensile experiments. Any other
      linear elastic parameter can be obtained from these two constants. By contrast,
      the physical responses of nonlinear elastic materials are generally described by
      parameters which are scalar functions of the deformation, and their particular
      choice is not always clear. Here, we review in a unified theoretical framework
      several nonlinear constitutive parameters, including the stretch modulus, the
      shear modulus and the Poisson function, that are defined for homogeneous
      isotropic hyperelastic materials and are measurable under axial or shear
      experimental tests. These parameters represent changes in the material properties
      as the deformation progresses, and can be identified with their linear equivalent
      when the deformations are small. Universal relations between certain of these
      parameters are further established, and then used to quantify nonlinear elastic
      responses in several hyperelastic models for rubber, soft tissue and foams. The
      general parameters identified here can also be viewed as a flexible basis for
      coupling elastic responses in multi-scale processes, where an open challenge is
      the transfer of meaningful information between scales.

PMID- 29225508
TI  - Theory of energy harvesting from heartbeat including the effects of pleural
      cavity and respiration.
AB  - Self-powered implantable devices with flexible energy harvesters are of
      significant interest due to their potential to solve the problem of limited
      battery life and surgical replacement. The flexible electronic devices made of
      piezoelectric materials have been employed to harvest energy from the motion of
      biological organs. Experimental measurements show that the output voltage of the
      device mounted on porcine left ventricle in chest closed environment decreases
      significantly compared to the case of chest open. A restricted-space deformation
      model is proposed to predict the impeding effect of pleural cavity, surrounding
      tissues, as well as respiration on the efficiency of energy harvesting from
      heartbeat using flexible piezoelectric devices. The analytical solution is
      verified by comparing theoretical predictions to experimental measurements. A
      simple scaling law is established to analyse the intrinsic correlations between
      the normalized output power and the combined system parameters, i.e. the
      normalized permitted space and normalized electrical load. The results may
      provide guidelines for optimization of in vivo energy harvesting from heartbeat
      or the motions of other biological organs using flexible piezoelectric energy
      harvesters.

PMID- 29225509
TI  - A minimization principle for transition paths of maximum flux for collective
      variables.
AB  - Considered is the construction of transition paths of conformational changes for
      proteins and other macromolecules, using methods that do not require the
      generation of dynamics trajectories. Special attention is given to the use of a
      reduced set of collective variables for describing such paths. A favored way to
      define transition paths is to seek channels through the transition state having
      cross sections with a high reactive flux (density of last hitting points of
      reactive trajectories). Given here is a formula for reactive flux that is
      independent of the parameterization of "collective variable space." This formula
      is needed for the principal curve of the reactive flux (as in the revised finite
      temperature string method) and for the maximum flux transition (MaxFlux) path.
      Additionally, a resistance functional is derived for narrow tubes, which when
      minimized yields a MaxFlux path. A strategy for minimization is outlined in the
      spirit of the string method. Finally, alternative approaches based on determining
      trajectories of high probability are considered, and it is observed that they
      yield paths that depend on the parameterization of collective variable space,
      except in the case of zero temperature, where such a path coincides with a
      MaxFlux path.

PMID- 29225511
TI  - The Crystalline Sponge Method: A Solvent-Based Strategy to Facilitate Noncovalent
      Ordered Trapping of Solid and Liquid Organic Compounds.
AB  - A strategy that leverages solvent effects to noncovalently trap solid and
      unstable liquid organic compounds within a crystalline sponge ({[(ZnI2)3(tris(4
      pyridyl)-1,3,5-triazine)2].x(CHCl3)}n) in a simple, mild, and efficient fashion
      for target molecule structure determination via X-ray diffraction is disclosed.
      Host-guest structures were obtained using third-generation synchrotron radiation,
      and new beamline hardware allowed rapid data collection in ~5-24 minutes. This is
      40-90% faster than previously reported crystalline sponge synchrotron datasets
      collected by us, and approximately a 150-720-fold decrease in time versus using a
      typical in-house diffractometer, effectively enabling the potential for high
      throughput analysis. The new target molecule inclusion method using methyl tert
      butyl ether (MTBE) solvent was demonstrated by trapping (E)-stilbene, vanillin, 4
      (trifluoromethyl)phenyl azide, and (+)-artemisinin (an antimalarial drug). The
      potential of guests to maximize intermolecular interactions with the crystalline
      sponge framework at the expense of attenuating intramolecular interactions (e.g.,
      pi-conjugation) was observed for (E)-stilbene. Trapping of vanillin and (+)
      artemisinin elicited single-crystal-to-single-crystal transformations where space
      group symmetry reduced from C2/c to P1 and C2, respectively, and the absolute
      configuration of (+)-artemisinin was determined through anomalous dispersion.

PMID- 29225510
TI  - Rotating stars in relativity.
AB  - Rotating relativistic stars have been studied extensively in recent years, both
      theoretically and observationally, because of the information they might yield
      about the equation of state of matter at extremely high densities and because
      they are considered to be promising sources of gravitational waves. The latest
      theoretical understanding of rotating stars in relativity is reviewed in this
      updated article. The sections on equilibrium properties and on nonaxisymmetric
      oscillations and instabilities in f-modes and r-modes have been updated. Several
      new sections have been added on equilibria in modified theories of gravity,
      approximate universal relationships, the one-arm spiral instability, on analytic
      solutions for the exterior spacetime, rotating stars in LMXBs, rotating strange
      stars, and on rotating stars in numerical relativity including both hydrodynamic
      and magnetohydrodynamic studies of these objects.

PMID- 29225512
TI  - Development of the Multiple Gene Knockout System with One-Step PCR in
      Thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius.
AB  - Multiple gene knockout systems developed in the thermoacidophilic crenarchaeon
      Sulfolobus acidocaldarius are powerful genetic tools. However, plasmid
      construction typically requires several steps. Alternatively, PCR tailing for
      high-throughput gene disruption was also developed in S. acidocaldarius, but
      repeated gene knockout based on PCR tailing has been limited due to lack of a
      genetic marker system. In this study, we demonstrated efficient homologous
      recombination frequency (2.8 * 104 +/- 6.9 * 103 colonies/MUg DNA) by optimizing
      the transformation conditions. This optimized protocol allowed to develop
      reliable gene knockout via double crossover using short homologous arms and to
      establish the multiple gene knockout system with one-step PCR (MONSTER). In the
      MONSTER, a multiple gene knockout cassette was simply and rapidly constructed by
      one-step PCR without plasmid construction, and the PCR product can be immediately
      used for target gene deletion. As an example of the applications of this
      strategy, we successfully made a DNA photolyase- (phr-) and arginine
      decarboxylase- (argD-) deficient strain of S. acidocaldarius. In addition, an
      agmatine selection system consisting of an agmatine-auxotrophic strain and argD
      marker was also established. The MONSTER provides an alternative strategy that
      enables the very simple construction of multiple gene knockout cassettes for
      genetic studies in S. acidocaldarius.

PMID- 29225513
TI  - An abrupt bleeding of the anteriorly- displaced sigmoid sinus: a rare
      complication of myringoplasty.
AB  - Background: The location of the sigmoid sinus within the mastoid cavity is quite
      variable. An anteriorly- displaced vertical segment of the sigmoid sinus
      constitutes an uncommon but dangerous anatomical variation that surgeons rarely
      encounter during surgery. In this variation, the sigmoid sinus lays underneath a
      very thin bony flap, which makes it easily damaged. Thus, an abrupt fatal
      bleeding might occur. Despite the many hypotheses about its origin (Chronic
      otitis media, hypopneumatization, etc.), the pathogenesis of this variation is
      still not completely understood. Case presentation: We present a case where the
      vertical segment of the left sigmoid sinus was encountered just underneath a one-
      millimeter bony flap in the posterior wall of the external auditory canal during
      an attempted myringoplasty. Conclusion: Anatomical variations of the sigmoid
      sinus are not uncommon, and the otolaryngologist should be aware of such
      variations to prevent unpleasant, intra- operative surprises.

PMID- 29225514
TI  - Elevation of small, dense low density lipoprotein cholesterol-a possible
      antecedent of atherogenic lipoprotein phenotype in type 2 diabetes patients in
      Jos, North-Central Nigeria.
AB  - Background: The global prevalence of type 2 diabetes is increasing. Dyslipidaemia
      is a known complication of diabetes mellitus manifesting frequently as
      cardiovascular diseases and stoke. Elevation of small, dense low density
      lipoprotein has been recognised as a component of the atherogenic lipoprotein
      phenotype associated with cardiovascular complications. We speculate that the
      elevation of this lipoprotein particle may be the antecedent of the atherogenic
      lipoprotein phenotype. This study therefore aims to determine the pattern of
      dyslipidaemia among diabetes mellitus patients in Jos, North-Central Nigeria.
      Methods: One hundred and seventy-six patients with type 2 diabetes and 154 age
      matched controls were studied. The patients with diabetes were regular clinic
      attenders and had stable glycaemic control. None were on lipid-lowering therapy.
      Anthropometric indices, blood pressure, and lipids (including total cholesterol,
      high density lipoprotein cholesterol, and triglyceride) were measured by chemical
      methods using the Hitachi 902 analyzer. Low density lipoprotein cholesterol was
      calculated using the Friedewald's equation. Small, dense low density lipoprotein
      cholesterol, -sdLDL-C was measured using the precipitation method by Hirano et
      al. Means of the different groups were compared using EPI Info and a P-value of
      <0.05 was accepted as significant difference. Results: Total cholesterol, low
      density lipoprotein cholesterol, triglyceride and small, dense lipoprotein
      cholesterol were all significantly higher in diabetes patients than controls
      except high density lipoprotein cholesterol. The percentage of LDL-C as sdLDL-C
      among the diabetes versus control group was 45% +/- 17.79 v 32.0% +/- 15.93.
      Serum sdLDL-C concentration was determined to be 1.45 +/- 0.64 among diabetes
      patients and 0.8 +/- 0.54 among control subjects. 75% of diabetes patients had
      hypertension and were taking blood pressure lowering medications. Conclusion: The
      classical atherogenic lipoprotein phenotype was not demonstrated among subjects
      with type 2 diabetes mellitus in this study, but the elevation of serum small
      dense low density lipoprotein cholesterol in patients with sustained hypertension
      suggests the establishment of atherogenic complications among our diabetes
      patients.

PMID- 29225515
TI  - Anticancer activity of Astragalus polysaccharide in human non-small cell lung
      cancer cells.
AB  - Background: We have reported that Chinese herbs Astragalus polysaccharide (APS)
      can inhibit nuclear factor kappaB (NF-kappaB) activity during the development of
      diabetic nephropathy in mice. NF-kappaB plays important roles in genesis, growth,
      development and metastasis of cancer. NF-kappaB is also involved in the
      development of treatment resistance in tumors. Here we investigated the antitumor
      activity of APS in human non-small cell lung cells (A549 and NCI-H358) and the
      related mechanisms of action. Methods: The dose-effect and time-effect of
      antitumor of APS were determined in human lung cancer cell line A549 and NCI
      H358. The inhibition effect of APS on the P65 mRNA and protein was detected by
      reverse transcriptase-PCR (RT-PCR) and Western blot in A549 cells respectively.
      The inhibition effect of APS on the p50, CyclinD1 and Bcl-xL protein was detected
      by Western blot in A549 cells respectively. The effect of APS on NF-kappaB
      transcription activity was measured with NF-kappaB luciferase detection. Finally,
      the nude mice A549 xenograft was introduced to confirm the antitumor activity of
      APS in vivo. Results: Cell viability detection results indicated that APS can
      inhibit the proliferation of human lung cancer cell line A549 and NCI-H358 in the
      concentration of 20 and 40 mg/mL. NF-kappaB activator Phorbol 12-myristate13
      acetate (PMA) can attenuate the antitumor activity of APS in both cell lines, but
      NF-kappaB inhibitor BAY 11-7082 (Bay) can enhance the effect of APS in both cell
      lines. In vivo APS can delay the growth of A549 xenograft in BALB/C nude mice.
      APS can down-regulate the expression of P65 mRNA and protein of A549 cells and
      decrease the expression of p50, CyclinD1 and Bcl-xL protein. The luciferase
      detection showed that the APS could reduce the P65 transcription activity in A549
      cells. PMA can partially alleviate the inhibition activity of P65 transcription
      activity of APS in A549 cells, and Bay can enhance the down-regulation of the P65
      transcription activity induced by APS in A549 cells. Conclusion: APS has a
      significant antitumor activity in human lung cancer cells A549 and NCI-H358. NF
      kappaB inhibition may mediate the antitumor effect.

PMID- 29225516
TI  - Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to
      temozolomide in human glioblastoma.
AB  - Background: Chemoresistance of glioblastoma (GBM) is a feature of this
      devastating disease. This study is to determine the relationship between Hedgehog
      (HH)/Gli1 signaling pathway and chemoresistance to temozolomide (TMZ) in human
      GBM. Methods: We analyzed Gli1 nuclear staining and O6-methylguanine DNA
      methyltransferase (MGMT) expression in 48 cases of primary GBM tissues by
      immunohistochemistry. Quantitative PCR, western blot, methylation-specific PCR,
      cell proliferation and apoptosis assay were used to investigate changes of MGMT
      expression and chemosensitivity to TMZ after manipulating HH/Gli1 signaling
      activity in A172 and U251 GBM cell lines. Chromatin immunoprecipitation assay was
      utilized to identify potential Gli1 potential binding sites in MGMT gene promoter
      region. We established GBM xenografts using U251 cells to assess whether
      inhibiting HH/Gli1 signaling activity restored chemosensitivity to TMZ. Results:
      O6-Methylguanine DNA methyltransferase-positive GBM tissues had a significantly
      higher rate of Gli1 nuclear staining than MGMT-negative ones (67.7% vs. 32.3%, p
      = 0.0159). Activation of HH/Gli1 signaling by pcDNA3.1-Gli1 cell transfection in
      A172 cells led to increased MGMT expression and enhanced resistance to TMZ
      treatment. Inhibition of the HH/Gli1 signaling by cyclopamine in U251 cells
      resulted in decreased MGMT expression and increased sensitivity to TMZ treatment.
      Both ways altered MGMT levels without changing the MGMT promoter methylation. The
      potential binding site of Gli1 in the MGMT gene promoter region was located at -
      411 to - 403 bp upstream the transcriptional start site. The in vivo study
      revealed a synergistic effect on tumor growth inhibition with the combined
      administration of cyclopamine and TMZ. Conclusions: This study shows that HH/Gli1
      signaling pathway regulates MGMT expression and chemoresistance to TMZ in human
      GBM independent from MGMT promoter methylation status, which offers a potential
      target to restore chemosensitivity to TMZ in a fraction of GBM with high MGMT
      expression.

PMID- 29225517
TI  - Intestinally-restricted Janus Kinase inhibition: a potential approach to maximize
      the therapeutic index in inflammatory bowel disease therapy.
AB  - Background: An unmet need remains for safe and effective treatments to induce and
      maintain remission in inflammatory bowel disease (IBD) patients. The Janus kinase
      (JAK) inhibitor, tofacitinib, has demonstrated robust efficacy in ulcerative
      colitis patients although, like other systemic immunosuppressants, there may be
      safety concerns associated with its use. This preclinical study evaluated whether
      modulating intestinal inflammation via local JAK inhibition can provide efficacy
      without systemic immunosuppression. Methods: The influence of tofacitinib, dosed
      orally or intracecally, on oxazolone-induced colitis, oxazolone or interferon
      gamma (IFNgamma)-induced elevation of colonic phosphorylated signal transducer
      and activator of transcription1 (pSTAT1) levels, and basal splenic natural killer
      (NK) cell counts was investigated in mice. Results: Tofacitinib, dosed orally or
      intracecally, inhibited, with similar efficacy, oxazolone-induced colitis,
      represented by improvements in the disease activity index and its sub-scores
      (body weight, stool consistency and blood content). Intracecal dosing of
      tofacitinib resulted in a higher colon:plasma drug exposure ratio compared to
      oral dosing. At equieffective oral and intracecal doses, colonic levels of
      tofacitinib were similar, while the plasma levels for the latter were markedly
      lower, consistent with a lack of effect on splenic NK cell counts. Tofacitinib,
      dosed orally, intracecally, or applied to the colonic lumen in vitro, produced
      dose-dependent, and maximal inhibition of oxazolone or IFNgamma-induced STAT1
      phosphorylation in the colon. Conclusions: Localized colonic JAK inhibition, by
      intracecal delivery of tofacitinib, provides colonic target engagement and
      efficacy in a mouse colitis model at doses which do not impact splenic NK cell
      counts. Intestinal targeting of JAK may permit separation of local anti
      inflammatory activity from systemic immunosuppression, and thus provide a larger
      therapeutic index compared to systemic JAK inhibitors.

PMID- 29225518
TI  - Implications for the Self Determine Benevolence and Self-Protection in Intergroup
      Relations.
AB  - People often favor groups they belong to over those beyond the in-group boundary.
      Yet, in-group favoritism does not always occur, and people will sometimes favor
      an out-group over the in-group. We delineate theoretically when in-group
      favoritism (i.e., self-protection) and out-group favoritism (i.e., benevolence)
      should occur. In two experiments, groups' relative status and competence
      stereotypes were manipulated; groups' outcomes were non-contingent in Experiment
      1 and contingent in Experiment 2. When allocating reward, members of a low status
      group were self-protective, favoring the in-group over the out-group under both
      non-contingent and contingent outcomes. Those with high status benevolently
      favored the out-group when outcomes were non-contingent, but were self-protective
      with contingent outcomes. People were willing to engage in social activities with
      an out-group member regardless of competence. However, when task collaboration
      had implications for the self, those with low status preferred competent over
      less competent out-group members. Traits of high status targets were
      differentiated by those with low status in both experiments, whereas those with
      high status differentiated low status members' traits only when outcomes were
      contingent. A general principle fits the data: the implications of intergroup
      responses for the self determine benevolence and self-protection. Implications
      for the Self Determine Benevolence and Self Protection in Intergroup Relations.

PMID- 29225519
TI  - The Feasibility of First Step to Success with Preschoolers.
AB  - The primary purpose of this study was to examine feasibility of the preschool
      version of the First Step to Success (FSS) intervention. Toward this end, the
      following four research questions were addressed: (1) To what extent was the
      intervention implemented with integrity? (2) To what extent do teachers and
      parents perceive the intervention to be socially valid? (3) To what extent were
      teachers and parents satisfied with the intervention? and (4) To what extent was
      the intervention effective in reducing problem behavior and improving social
      skills? Twelve students participated in the study. Treatment integrity, social
      validity, and satisfaction results were analyzed at the aggregate level, and a
      reliable change index was calculated at the case level for primary outcome
      measures to assess the potential efficacy of the intervention. Fidelity data
      suggest the preschool version of the intervention can be implemented with
      acceptable integrity by coaches and teachers in preschool settings. Social
      validity outcomes suggest parents' perceptions of the program's goals,
      procedures, and outcomes were extremely favorable, and social validity from the
      teacher perspective was acceptable. The results provide initial evidence that
      participating in the preschool version of the FSS intervention improves
      children's social skills and decreases problem behavior.

PMID- 29225520
TI  - Epilepsy Treatment: A Futurist View.
AB  - Advances in epilepsy treatment are occurring at a rapid pace, and it is
      challenging for us to keep up with the latest in our field. As we struggle to
      keep up with the literature and concentrate on our own research and clinical
      work, we often fail to exercise our imagination and envision what our field will
      be like in future decades. This was the assignment to the speakers for the
      Presidential Symposium at the 2016 American Epilepsy Society Annual Meeting. I
      challenged the experts to step outside the frame of their usual daily work to
      imagine what epilepsy treatment would and should look like for the next
      generation of epilepsy specialists and their patients. As you will read in the
      following sections, the speakers truly stepped up to the challenge to look into
      the crystal ball. The following are summaries of each lecture that describe the
      current state, existing cutting edge ideas, and some surprising predictions for
      the future. I am grateful for the tremendous effort these experts put into this
      challenge and hope they stimulate your imagination so you will work to bring
      these advances to our patients.

PMID- 29225521
TI  - Current Status of Treatments for Children with Electrical Status in Slow-Wave
      Sleep (ESES/CSWS).

PMID- 29225522
TI  - How Closely Should We Monitor for Nocturnal Seizures?

PMID- 29225523
TI  - Resting Connectivity in Non-lesional Temporal Lobe Epilepsy.

PMID- 29225524
TI  - New (fMRI) Versus Old (Direct Cortical Stimulation) Technology: Which Is Prime
      Time for Language Mapping?

PMID- 29225525
TI  - Depression and Epilepsy: We Are No Longer One Direction.

PMID- 29225526
TI  - Scratching the Surface in Autoimmune Epilepsy: It is the Time to Dig Deeper, But
      How?

PMID- 29225527
TI  - Epileptic Activity and Cognitive Impairment: Hijacking Plasticity During Sleep.

PMID- 29225528
TI  - How Have We Come This Far? Epilepsy Classification Through the Ages.

PMID- 29225529
TI  - The Big Picture: Systems Biology Approach to Antiepileptic Drug Discovery.

PMID- 29225530
TI  - Two Targets Are Better Than One: A New Strategy to Increase the Specificity of
      Anti-Epileptic Drugs.

PMID- 29225531
TI  - Mom Genes: A Role for Loss of Maternal Ube3a in GABAergic Neurons in Angelman
      Syndrome.

PMID- 29225532
TI  - Understanding Network Connections Connects Genotype to Epilepsy Phenotype.

PMID- 29225533
TI  - Degrading Seizures (or, Playing Tag with Nedd4-2).

PMID- 29225534
TI  - Opposing Phenotypes in Dravet Syndrome Patient-Derived Induced Pluripotent Stem
      Cell Neurons: Can Everyone Be Right?

PMID- 29225535
TI  - Myoclonus After Cardiac Arrest: Where Do We Go From Here?
AB  - Prognostication after cardiac arrest often depends primarily on neurological
      function, and characterizing the extent of neurological injury hinges on
      neurophysiological testing and clinical neurological examination. The presence of
      early posthypoxic myoclonus (PHM) following cardiac arrest had been invariably
      associated with poor outcome, but more recent studies have shown that those with
      early PHM may survive with good neurological function. Electroencephalographic
      patterns suggestive of severe brain injury may be more valuable than the presence
      of PHM itself in portending poor functional status, and phenotyping PHM may also
      be useful in delineating benign and malignant forms. Patients with early PHM
      should be evaluated similarly to others who suffer cardiac arrest by using a
      multimodal approach in determining prognosis until further studies are performed
      that better characterize early PHM subtypes and their outcomes.

PMID- 29225536
TI  - A Genetic Disposition for Autoimmune Encephalitis: Searching for Human Leukocyte
      Antigen (HLA) Complex Subtypes.

PMID- 29225537
TI  - Social and Cognitive Outcome from Childhood-Onset Epilepsy: Do We Have Some Good
      News?

PMID- 29225538
TI  - Ketogenic Diet: It Has a Role in Our Armamentarium of Treatment of Refractory
      Seizures.

PMID- 29225539
TI  - Anticonvulsant Effects of Cannabidiol in Dravet Syndrome.

PMID- 29225540
TI  - The 'Thalamic Hubness' of Anterior Temporal Lobectomy Outcome.

PMID- 29225541
TI  - Should You Use ACTH or Vigabatrin for Infantile Spasms? Or Why Not Use Both
      Together?

PMID- 29225542
TI  - The Plausibility of an Association Between Maternal Obesity and Onset of
      Childhood Epilepsy: A Well-Rounded, Robust Argument or a Thin Epidemiologic
      Association?

PMID- 29225543
TI  - Dropping the Sectioning of the Anterior Corpus Callosum for Drop Attacks.

PMID- 29225544
TI  - Novel Targets for Developing Antiseizure and, Potentially, Antiepileptogenic
      Drugs.
AB  - Epilepsy is a chronic neurological disorder caused by abnormal changes in the
      functions of neuronal circuits and manifested by seizures. It affects patients of
      all age, substantially worsens the quality of life for the patients as well as
      their families, and imposes a huge economic burden on the healthcare system.
      Historically, efforts for discovering and developing antiseizure therapies have
      been focused on modulating the functions of receptors, transporters, and enzymes
      expressed by neurons. These drug development efforts have paid off, as we have
      over 25 antiseizure drugs available in the clinic. However, these drugs mainly
      provide symptomatic relief from seizures and often cause serious adverse effects.
      Importantly, almost one-third of patients with epilepsy do not have their
      seizures adequately controlled by available drugs. To address this problem,
      researchers are investigating cellular and molecular mechanisms fundamental to
      the optimal function of neuronal circuits. Evidence shows that disruptions in
      these mechanisms cause impairment in neuroglial interactions, uncontrolled
      inflammation, aberrant synaptogenesis, and neurodegeneration in genetic and
      acquired epilepsies. Many novel therapeutic targets have been identified to
      target these mechanisms for developing new antiseizure drugs. In addition, the
      field is exploring new drug targets which may impede the development of epilepsy.
      We have summarized some of these novel targets in this brief review.

PMID- 29225545
TI  - Let's Be Superficial About Ictal Activity.

PMID- 29225546
TI  - Leaks That Could Kill.

PMID- 29225547
TI  - Everybody's Got the Fever...Be it Fahrenheit or Centigrade.

PMID- 29225548
TI  - Modulation of Abnormal Sodium Channel Currents in Heart and Brain: Hope for SUDEP
      Prevention and Seizure Reduction.

PMID- 29225549
TI  - You Have Brains in Your Head, You Have Organoids in Your Dish, You Can Steer
      Yourself in any Direction You Wish.

PMID- 29225550
TI  - Theta is the New Alpha.

PMID- 29225551
TI  - It's Current.

PMID- 29225552
TI  - A GRAPH PARTITIONING APPROACH TO PREDICTING PATTERNS IN LATERAL INHIBITION
      SYSTEMS.
AB  - We analyze spatial patterns on networks of cells where adjacent cells inhibit
      each other through contact signaling. We represent the network as a graph where
      each vertex represents the dynamics of identical individual cells and where graph
      edges represent cell-to-cell signaling. To predict steady-state patterns we find
      equitable partitions of the graph vertices and assign them into disjoint classes.
      We then use results from monotone systems theory to prove the existence of
      patterns that are structured in such a way that all the cells in the same class
      have the same final fate. To study the stability properties of these patterns, we
      rely on the graph partition to perform a block decomposition of the system. Then,
      to guarantee stability, we provide a small-gain type criterion that depends on
      the input-output properties of each cell in the reduced system. Finally, we
      discuss pattern formation in stochastic models. With the help of a modal
      decomposition we show that noise can enhance the parameter region where
      patterning occurs.

PMID- 29225553
TI  - Brain Imaging of Human Sexual Response: Recent Developments and Future
      Directions.
AB  - Purpose of Review: The purpose of this study is to provide a comprehensive
      summary of the latest developments in the experimental brain study of human
      sexuality, focusing on brain connectivity during the sexual response. Recent
      Findings: Stable patterns of brain activation have been established for different
      phases of the sexual response, especially with regard to the wanting phase, and
      changes in these patterns can be linked to sexual response variations, including
      sexual dysfunctions. From this solid basis, connectivity studies of the human
      sexual response have begun to add a deeper understanding of the brain network
      function and structure involved. Summary: The study of "sexual" brain
      connectivity is still very young. Yet, by approaching the brain as a connected
      organ, the essence of brain function is captured much more accurately, increasing
      the likelihood of finding useful biomarkers and targets for intervention in
      sexual dysfunction.

PMID- 29225554
TI  - Recent Developments in Psychopharmaceutical Approaches to Treating Female Sexual
      Interest and Arousal Disorder.
AB  - Purpose of Review: This review summarizes the recent literature and empirical
      studies on psychopharmacological approaches to treating female sexual
      interest/arousal disorder (FSIAD). Recent Findings: Several new drugs for FSIAD
      that are intended to increase sexual responsiveness by influencing central
      excitatory and inhibitory neuromodulatory processes are under development.
      Studies on flibanserin resulted in the first approved medication for the
      treatment of low sexual desire in premenopausal women. New drugs under
      development are testosterone combined with sildenafil or buspiron, bremelanotide,
      BP101, and nasal testosterone (TBS-2). Summary: Although pharmacological
      enhancement of sexual responsiveness may be potentially helpful in the treatment
      of FSIAD, the observed effects of flibanserin and other new drugs under
      development seem limited in terms of clinical significance. Given the
      multifactorial character of FSIAD, it may be important to integrate
      psychopharmacological treatment with sex therapy for optimal treatment efficacy.

PMID- 29225555
TI  - Lending A Hand: Detecting Hands and Recognizing Activities in Complex Egocentric
      Interactions.
AB  - Hands appear very often in egocentric video, and their appearance and pose give
      important cues about what people are doing and what they are paying attention to.
      But existing work in hand detection has made strong assumptions that work well in
      only simple scenarios, such as with limited interaction with other people or in
      lab settings. We develop methods to locate and distinguish between hands in
      egocentric video using strong appearance models with Convolutional Neural
      Networks, and introduce a simple candidate region generation approach that
      outperforms existing techniques at a fraction of the computational cost. We show
      how these high-quality bounding boxes can be used to create accurate pixelwise
      hand regions, and as an application, we investigate the extent to which hand
      segmentation alone can distinguish between different activities. We evaluate
      these techniques on a new dataset of 48 first-person videos of people interacting
      in realistic environments, with pixel-level ground truth for over 15,000 hand
      instances.

PMID- 29225556
TI  - An Optimal Transportation based Univariate Neuroimaging Index.
AB  - The alterations of brain structures and functions have been considered closely
      correlated to the change of cognitive performance due to neurodegenerative
      diseases such as Alzheimer's disease. In this paper, we introduce a variational
      framework to compute the optimal transformation (OT) in 3D space and propose a
      univariate neuroimaging index based on OT to measure such alterations. We compute
      the OT from each image to a template and measure the Wasserstein distance between
      them. By comparing the distances from all the images to the common template, we
      obtain a concise and informative index for each image. Our framework makes use of
      the Newton's method, which reduces the computational cost and enables itself to
      be applicable to large-scale datasets. The proposed work is a generic approach
      and thus may be applicable to various volumetric brain images, including
      structural magnetic resonance (sMR) and fluorodeoxyglucose positron emission
      tomography (FDG-PET) images. In the classification between Alzheimer's disease
      patients and healthy controls, our method achieves an accuracy of 82.30% on the
      Alzheimers Disease Neuroimaging Initiative (ADNI) baseline sMRI dataset and
      outperforms several other indices. On FDG-PET dataset, we boost the accuracy to
      88.37% by leveraging pairwise Wasserstein distances. In a longitudinal study, we
      obtain a 5% significance with p-value = 1.13*105 in a t-test on FDG-PET. The
      results demonstrate a great potential of the proposed index for neuroimage
      analysis and the precision medicine research.

PMID- 29225557
TI  - Toward the Development of a Flexible Mesoscale MRI-compatible Neurosurgical
      Continuum Robot.
AB  - Brain tumor, be it primary or metastatic, is usually life threatening for a
      person of any age. Primary surgical resection which is one of the most effective
      ways of treating brain tumors can have tremendously increased success rate if the
      appropriate imaging modality is used for complete tumor resection. Magnetic
      resonance imaging (MRI) is the imaging modality of choice for brain tumor imaging
      because of its excellent soft-tissue contrast. MRI combined with continuum soft
      robotics has immense potential to be the next major technological breakthrough in
      the field of brain cancer diagnosis and therapy. In this work, we present the
      design, kinematic, and force analysis of a flexible spring-based minimally
      invasive neurosurgical intracranial robot (MINIR-II). It is comprised of an inter
      connected inner spring and an outer spring and is connected to actively cooled
      shape memory alloy spring actuators via tendon driven mechanism. Our robot has
      three serially connected 2-DoF segments which can be independently controlled due
      to the central tendon routing configuration. The kinematic and force analysis of
      the robot and the independent segment control were verified by experiments. Robot
      motion under forced cooling of SMA springs was evaluated as well as the MRI
      compatibility of the robot and its motion capability in brainlike gelatin
      environment.

PMID- 29225558
TI  - Vulvar squamous cell carcinoma aggressiveness is associated with differential
      expression of collagen and STAT1.
AB  - Background: Vulvar squamous cell carcinoma (vSCC) is a rare but debilitating
      disease. One vSCC variant comprises tumor cells that grow and expand as a
      cohesive sheet of cells that "pushes" and compresses the associated
      lymphoplasmacytic (LPC) stroma. Another vSCC variant features tumor cells that
      grow in loose association with one another and infiltrate the associated
      fibromyxoid (FMX) stroma consisting mainly of extracellular matrix. Clinically,
      infiltrative vSCC with FMX stroma (Inf/FMX) is significantly associated with
      lymph node metastases and recurrence. Methods: An unbiased proteomic approach was
      used to identify pathways involved in the development of the different vSCC
      variants. Proteins extracted from formalin-fixed and paraffin-embedded tissues of
      10 cases of pushing vSCC with LPC stroma (Push/LPC) and eight cases of Inf/FMX
      were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      Results: Analysis identified 2265 different proteins in the 18 samples of vSCC.
      Of these, 282 proteins were differentially expressed between vSCC variants. Of
      these, 45 were higher and 237 lower in Inf/FMX compared to Push/LPC tumors.
      Consistent with the desmoplastic morphology and increased picrosirius red
      staining, expression of subunits of several collagens (Col 1, 3, 6, 14) was
      higher in the more aggressive Inf/FMX tumors. In contrast, signal transducer and
      activator of transcription 1 (STAT1), an important regulator of several
      inflammatory pathways, was expressed at lower levels in the Inf/FMX tumors. This
      finding was confirmed by immunohistochemistry using an antibody to STAT1.
      Informatics analysis of the differing profiles identified differences in pathways
      associated with integrin signaling and inflammation mediated by chemokines and
      cytokines. Conclusions: Comparing the proteomic profiles of vSCC morphologic
      variants indicates that increased expression of collagen subunits and decreased
      expression of STAT1 are associated with a more aggressive tumor variant, defined
      by increased incidence of nodal metastases and tumor recurrence. Informatic
      analyses further identify that both alterations in cell interaction with matrix
      and immune function differ with tumor aggressiveness. Identification of these
      pathways provides a molecular basis for understanding aggressiveness of vSCC.

PMID- 29225560
TI  - A laparoscopic training model for surgical trainees.

PMID- 29225559
TI  - Hormesis and Homeopathy: Toward a New Self-Consciousness.

PMID- 29225561
TI  - Nanoscale thermal phenomena in the vicinity of magnetic nanoparticles in
      alternating magnetic fields.
AB  - Magnetic nanoparticles can be made to dissipate heat to their immediate
      surroundings in response to an applied alternating magnetic field. This property,
      combined with the biocompatibility of iron oxide nanoparticles and the ability of
      magnetic fields to penetrate deep in the body, makes magnetic nanoparticles
      attractive in a range of biomedical applications where thermal energy is used
      either directly to achieve a therapeutic effect or indirectly to actuate the
      release of a therapeutic agent. Although the concept of bulk heating of fluids
      and tissues using energy dissipated by magnetic nanoparticles has been well
      accepted and applied for several decades, many new and exciting biomedical
      applications of magnetic nanoparticles take advantage of heat effects that are
      confined to the immediate nanoscale vicinity of the nanoparticles. Until recently
      the existence of these nanoscale thermal phenomena had remained controversial. In
      this short review we summarize some of the recent developments in this field and
      emerging applications for nanoscale thermal phenomena in the vicinity of magnetic
      nanoparticles in alternating magnetic fields.

PMID- 29225562
TI  - Varying age-gender associations between body mass index and urban greenspace.
AB  - Urban greenspace benefits urbanites in numerous ways ranging from regulating
      flooding, air quality, and local climate to providing opportunities for exercise
      and relaxation. These benefits may influence human health. Greenspace, for
      example, may facilitate exercise, thereby helping to reduce body mass index (BMI)
      and combat obesity, a current epidemic of great public health concern. Little
      evidence exists to support this assertion, however, and we lack a full
      understanding of the mechanisms whereby this relationship operates, the
      populations for whom greenspace is linked to weight status, and the aspects of
      urban greenspace that are linked to weight status. This study seeks to identify
      relationships among the composition and arrangement of greenspace and BMI for
      different populations using regression models for eight age and gender groups in
      Cleveland, Ohio, US. We find that several greenspace variables are related to BMI
      for women under 65 years and males under 51 years, but not for older groups, and
      that the aspects and types of greenspace that are significantly related to BMI
      vary among groups. Relationships between greenspace attributes and BMI are
      generally stronger for female groups and for younger groups. Providing access to
      greenspace with particular attributes such as greenspaces with water, canopy
      cover, or connected greenspaces could support a healthy weight status for some
      populations, but these attributes are not consistent across age and gender
      groups. These results could help to inform policy aimed at designing urban
      greenspace to benefit the health of different population subgroups.

PMID- 29225563
TI  - Music-Evoked Emotions-Current Studies.
AB  - The present study is focused on a review of the current state of investigating
      music-evoked emotions experimentally, theoretically and with respect to their
      therapeutic potentials. After a concise historical overview and a schematic of
      the hearing mechanisms, experimental studies on music listeners and on music
      performers are discussed, starting with the presentation of characteristic
      musical stimuli and the basic features of tomographic imaging of emotional
      activation in the brain, such as functional magnetic resonance imaging (fMRI) and
      positron emission tomography (PET), which offer high spatial resolution in the
      millimeter range. The progress in correlating activation imaging in the brain to
      the psychological understanding of music-evoked emotion is demonstrated and some
      prospects for future research are outlined. Research in psychoneuroendocrinology
      and molecular markers is reviewed in the context of music-evoked emotions and the
      results indicate that the research in this area should be intensified. An
      assessment of studies involving measuring techniques with high temporal
      resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event
      related brain potentials (ERP), magnetoencephalography (MEG), skin conductance
      response (SCR), finger temperature, and goose bump development (piloerection) can
      yield information on the dynamics and kinetics of emotion. Genetic investigations
      reviewed suggest the heredity transmission of a predilection for music.
      Theoretical approaches to musical emotion are directed to a unified model for
      experimental neurological evidence and aesthetic judgment. Finally, the reports
      on musical therapy are briefly outlined. The study concludes with an outlook on
      emerging technologies and future research fields.

PMID- 29225564
TI  - Revealing the Radial Effect on Orientation Discrimination by Manual Reaction
      Time.
AB  - It has been shown that the sensitivity and accuracy of orientation perception in
      the periphery is significantly better when the orientations are radial with
      respect to the fixation point than when they are tangential. However, since
      perception and action may be dissociated, it is unclear whether the perceptual
      radial effect has a counterpart in reaction time (RT) of motor responses.
      Furthermore, it is unknown whether or how stimulus-response-compatibility (SRC)
      effect interacts with the radial effect to determine RT. To address these
      questions, we measured subjects' manual RT to grating stimuli that appeared
      across upper visual field (VF). We found that (1) RTs were significantly shorter
      when a grating was oriented closer to the radial direction than when it was
      oriented closer to the tangential direction even though the perceptual accuracies
      for the more radial and more tangential orientations were not significantly
      different under our experimental condition; (2) This RT version of the radial
      effect was larger in the left VF than in the right VF; (3) The radial effect and
      SRC effect interacted with each other to determine the overall RT. These results
      suggest that the RT radial effect reported here is not a passive reflection of
      the radial effect in perceptual accuracy, but instead, represents different
      processing time of radial and tangential orientations along the sensorimotor
      pathway.

PMID- 29225565
TI  - Commentary: Emergence of a Stable Cortical Map for Neuroprosthetic Control.

PMID- 29225566
TI  - Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in
      Hippocampal Pyramidal Neurons.
AB  - Psychostimulant drugs of abuse increase dendritic spine density in reward centers
      of the brain. However, little is known about their effects in the hippocampus,
      where activity-dependent changes in the density of dendritic spine are associated
      with learning and memory. Recent reports suggest that Cdk5 plays an important
      role in drug addiction, but its role in psychostimulant's effects on dendritic
      spines in hippocampus remain unknown. We used in vivo and in vitro approaches to
      demonstrate that amphetamine increases dendritic spine density in pyramidal
      neurons of the hippocampus. Primary cultures and organotypic slice cultures were
      used for cellular, molecular, pharmacological and biochemical analyses of the
      role of Cdk5/p25 in amphetamine-induced dendritic spine formation. Amphetamine
      (two-injection protocol) increased dendritic spine density in hippocampal neurons
      of thy1-green fluorescent protein (GFP) mice, as well as in hippocampal cultured
      neurons and organotypic slice cultures. Either genetic or pharmacological
      inhibition of Cdk5 activity prevented the amphetamine-induced increase in
      dendritic spine density. Amphetamine also increased spine density in neurons
      overexpressing the strong Cdk5 activator p25. Finally, inhibition of calpain, the
      protease necessary for the conversion of p35 to p25, prevented amphetamine's
      effect on dendritic spine density. We demonstrate, for the first time, that
      amphetamine increases the density of dendritic spine in hippocampal pyramidal
      neurons in vivo and in vitro. Moreover, we show that the Cdk5/p25 signaling and
      calpain activity are both necessary for the effect of amphetamine on dendritic
      spine density. The identification of molecular mechanisms underlying
      psychostimulant effects provides novel and promising therapeutic approaches for
      the treatment of drug addiction.

PMID- 29225568
TI  - Age-Dependent, Subunit Specific Action of Hydrogen Sulfide on GluN1/2A and
      GluN1/2B NMDA Receptors.
AB  - Hydrogen sulfide (H2S) is an endogenously produced neuroactive gas implicated in
      many key processes in the peripheral and central nervous system. Whereas the
      neuroprotective role of H2S has been shown in adult brain, the action of this
      messenger in newborns remains unclear. One of the known targets of H2S in the
      nervous system is the N-methyl-D-aspartate (NMDA) glutamate receptor which can be
      composed of different subunits with distinct functional properties. In the
      present study, using patch clamp technique, we compared the effects of the H2S
      donor sodium hydrosulfide (NaHS, 100 MUM) on hippocampal NMDA receptor mediated
      currents in rats of the first and third postnatal weeks. This was supplemented by
      testing effects of NaHS on recombinant GluN1/2A and GluN1/2B NMDA receptors
      expressed in HEK293T cells. The main finding is that NaHS action on NMDA currents
      is age-dependent. Currents were reduced in newborns but increased in older
      juvenile rats. Consistent with an age-dependent switch in NMDA receptor
      composition, in HEK239T cells expressing GluN1/2A receptors, NaHS increased NMDA
      activated currents associated with acceleration of desensitization and decrease
      of the deactivation rate. In contrast, in GluN1/2B NMDA receptors, which are
      prevalent in newborns, NaHS decreased currents and reduced receptor deactivation
      without effect on the desensitization rate. Adenylate cyclase inhibitor MDL
      12330A (10 MUM) did not prevent the age-dependent effects of NaHS on NMDA evoked
      currents in pyramidal neurons of hippocampus. The reducing agent dithiothreitol
      (DTT, 2 mM) applied on HEK293T cells prevented facilitation induced by NaHS on
      GluN1/2A NMDA receptors, however in GluN1/2B NMDA receptors the inhibitory effect
      of NaHS was still observed. Our data indicate age-dependent effect of H2S on NMDA
      receptor mediated currents determined by glutamate receptor subunit composition.
      While the inhibitory action of H2 on GluN1/2B receptors could limit the excessive
      activation in early age, the enhanced functionality of GluN1/2A receptor in the
      presence of this gasotransmitter can enlarge synaptic efficacy and promote
      synaptic plasticity in adults.

PMID- 29225567
TI  - The Nanoworld of the Tripartite Synapse: Insights from Super-Resolution
      Microscopy.
AB  - Synaptic connections between individual nerve cells are fundamental to the
      process of information transfer and storage in the brain. Over the past decades a
      third key partner of the synaptic machinery has been unveiled: ultrathin
      processes of electrically passive astroglia which often surround pre- and
      postsynaptic structures. The recent advent of super-resolution (SR) microscopy
      has begun to uncover the dynamic nanoworld of synapses and their astroglial
      environment. Here we overview and discuss the current progress in our
      understanding of the synaptic nanoenvironment, as gleaned from the imaging
      methods that go beyond the diffraction limit of conventional light microscopy. We
      argue that such methods are essential to achieve a new level of comprehension
      pertinent to the principles of signal integration in the brain.

PMID- 29225569
TI  - Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord
      Abolishes the Generation of Locomotor Activity.
AB  - The contribution of left-right reciprocal coupling between spinal locomotor
      networks to the generation of locomotor activity was tested in adult lampreys.
      Muscle recordings were made from normal animals as well as from experimental
      animals with rostral midline (ML) spinal lesions (~13%->35% body length, BL),
      before and after spinal transections (T) at 35% BL. Importantly, in the present
      study actual locomotor movements and muscle burst activity, as well as other
      motor activity, were initiated in whole animals by descending brain-spinal
      pathways in response to sensory stimulation of the anterior head. For
      experimental animals with ML spinal lesions, sensory stimulation could elicit
      well-coordinated locomotor muscle burst activity, but with some significant
      differences in the parameters of locomotor activity compared to those for normal
      animals. Computer models representing normal animals or experimental animals with
      ML spinal lesions could mimic many of the differences in locomotor activity. For
      experimental animals with ML and T spinal lesions, right and left rostral hemi
      spinal cords, disconnected from intact caudal cord, usually produced tonic or
      unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or
      sensory-evoked relatively high frequency "burstlet" activity that probably is
      analogous to the previously described in vitro "fast rhythm", which is thought to
      represent lamprey locomotor activity. However, "burstlet" activity in the present
      study had parameters and features that were very different than those for lamprey
      locomotor activity: average frequencies were ~25 Hz, but individual frequencies
      could be >50 Hz; burst proportions (BPs) often varied with cycled time;
      "burstlet" activity usually was not accompanied by a rostrocaudal phase lag; and
      following ML spinal lesions alone, "burstlet" activity could occur in the
      presence or absence of swimming burst activity, suggesting the two were generated
      by different mechanisms. In summary, for adult lampreys, left and right hemi
      spinal cords did not generate rhythmic locomotor activity in response to
      descending inputs from the brain, suggesting that left-right reciprocal coupling
      of spinal locomotor networks contributes to both phase control and
      rhythmogenesis. In addition, the present study indicates that extreme caution
      should be exercised when testing the operation of spinal locomotor networks using
      artificial activation of isolated or reduced nervous system preparations.

PMID- 29225570
TI  - Flexible and Stable Value Coding Areas in Caudate Head and Tail Receive
      Anatomically Distinct Cortical and Subcortical Inputs.
AB  - Anatomically distinct areas within the basal ganglia encode flexible- and stable
      value memories for visual objects (Hikosaka et al., 2014), but an important
      question remains: do they receive inputs from the same or different brain areas
      or neurons? To answer this question, we first located flexible and stable value
      coding areas in the caudate head (CDh) and caudate tail (CDt) of two rhesus
      macaque monkeys, and then injected different retrograde tracers into these areas
      of each monkey. We found that CDh and CDt received different inputs from several
      cortical and subcortical areas including temporal cortex, prefrontal cortex,
      cingulate cortex, amygdala, claustrum and thalamus. Superior temporal cortex and
      inferior temporal cortex projected to both CDh and CDt, with more CDt-projecting
      than CDh-projecting neurons. In superior temporal cortex and dorsal inferior
      temporal cortex, layers 3 and 5 projected to CDh while layers 3 and 6 projected
      to CDt. Prefrontal and cingulate cortex projected mostly to CDh bilaterally, less
      to CDt unilaterally. A cluster of neurons in the basolateral amygdala projected
      to CDt. Rostral-dorsal claustrum projected to CDh while caudal-ventral claustrum
      projected to CDt. Within the thalamus, different nuclei projected to either CDh
      or CDt. The medial centromedian nucleus and lateral parafascicular nucleus
      projected to CDt while the medial parafascicular nucleus projected to CDh. The
      inferior pulvinar and lateral dorsal nuclei projected to CDt. The ventral
      anterior and medial dorsal nuclei projected to CDh. We found little evidence of
      neurons projecting to both CDh and CDt across the brain. These data suggest that
      CDh and CDt can control separate functions using anatomically separate circuits.
      Understanding the roles of these striatal projections will be important for
      understanding how value memories are created and stored.

PMID- 29225571
TI  - Heterogenic Distribution of Aromatic L-Amino Acid Decarboxylase Neurons in the
      Rat Spinal Cord.
AB  - Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the
      synthesis of serotonin, dopamine, and certain trace amines and is present in a
      variety of organs including the brain and spinal cord. It is previously reported
      that in mammalian spinal cord AADC cells (called D-cells) were largely confined
      to a region around the central canal and that they do not produce monoamines. To
      date, there has not been a detailed description of their distribution and
      morphology in mammals. In the present study this issue is systematically
      investigated using immunohistochemistry. We have found that AADC cells in the rat
      spinal cord are both more numerous and more widely distributed than previously
      reported. In the gray matter, AADC neurons immunolabeled for NeuN were not only
      found in the region around the central canal but also in the dorsal horn,
      intermediate zone, and ventral horn. In the white matter a large number of glial
      cells were AADC-immunopositive in different spinal segments and the vast majority
      of these cells expressed oligodendrocyte and radial glial phenotypes.
      Additionally, a small number of AADC neurons labeled for NeuN were found in the
      white matter along the ventral median fissure. The shapes and sizes of AADC
      neurons varied according to their location. For example, throughout cervical and
      lumbar segments AADC neurons in the intermediate zone and ventral horn tended to
      be rather large and weakly immunolabeled, whereas those in comparable regions of
      sacrocaudal segments were smaller and more densely immunolabeled. The diverse
      morphological characteristics of the AADC cells suggests that they could be
      further divided into several subtypes. These results indicate that AADC cells are
      heterogeneously distributed in the rat spinal cord and they may exert different
      functions in different physiological and pathological situations.

PMID- 29225573
TI  - Commentary: Methamphetamine abuse impairs motor cortical plasticity and function.

PMID- 29225572
TI  - Adaptive Changes in the Sensitivity of the Dorsal Raphe and Hypothalamic
      Paraventricular Nuclei to Acute Exercise, and Hippocampal Neurogenesis May
      Contribute to the Antidepressant Effect of Regular Treadmill Running in Rats.
AB  - Increasing clinical evidence suggests that regular physical exercise can prevent
      or reduce the incidence of stress-related psychiatric disorders including
      depressive symptoms. Antidepressant effect of regular exercise may be implicated
      in monoaminergic transmission including serotonergic transmission, activation of
      the hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis, but
      few general concepts regarding the optimal exercise regimen for stimulating
      neural mechanisms involved in antidepressant properties have been developed.
      Here, we examined how 4 weeks of treadmill running at different intensities (0,
      15, 25 m/min, 60 min/day, 5 times/week) alters neuronal activity in the dorsal
      raphe nucleus (DRN), which is the major source of serotonin (5-HT) neurons in the
      central nervous system, and the hypothalamic paraventricular nucleus (PVN), in
      which corticotropin-releasing factor (CRF) neurons initiate the activation of the
      HPA axis, during one session of acute treadmill running at different speeds (0,
      15, 25 m/min, 30 min) in male Wistar rats, using c-Fos immunohistochemistry. We
      also examined neurogenesis in the hippocampus using immunohistochemistry for
      doublecortin (DCX) and assessed depressive-like behavior using the forced swim
      test after regular exercise for 4 weeks. In the pre-training period, acute
      treadmill running at low speed, but not at high speed, increased c-Fos positive
      nuclei in the DRN compared with the sedentary control. The number of c-Fos
      positive nuclei in the PVN during acute treadmill running was increased in a
      running speed-dependent manner. Regular exercise for 4 weeks, regardless of the
      training intensity, induced an enhancement of c-Fos expression in the DRN during
      not only low-speed but also high-speed acute running, and generally reduced c-Fos
      expression in the PVN during acute running compared with pre-training.
      Furthermore, regular treadmill running for 4 weeks enhanced DCX immunoreactivity
      in the hippocampal dentate gyrus (DG), and resulted in decreased depressive-like
      behavior, regardless of the training intensity. These results suggest that long
      term repeated exercise, regardless of the training intensity, improves depressive
      like behavior through adaptive changes in the sensitivity of DRN and PVN neurons
      to acute exercise, and hippocampal neurogenesis.

PMID- 29225574
TI  - Motor Unit Activity during Fatiguing Isometric Muscle Contraction in Hemispheric
      Stroke Survivors.
AB  - Enhanced muscle weakness is commonly experienced following stroke and may be
      accompanied by increased susceptibility to fatigue. To examine the contributions
      of central and peripheral factors to isometric muscle fatigue in stroke
      survivors, this study investigates changes in motor unit (MU) mean firing rate,
      and action potential duration during, and directly following, a sustained
      submaximal fatiguing contraction at 30% maximum voluntary contraction (MVC). A
      series of short contractions of the first dorsal interosseous muscle were
      performed pre- and post-fatigue at 20% MVC, and again following a 10-min recovery
      period, by 12 chronic stroke survivors. Individual MU firing times were extracted
      using surface EMG decomposition and used to obtain the spike-triggered average MU
      action potential waveforms. During the sustained fatiguing contraction, the mean
      rate of change in firing rate across all detected MUs was greater on the affected
      side (-0.02 +/- 0.03 Hz/s) than on the less-affected side (-0.004 +/- 0.003 Hz/s,
      p = 0.045). The change in firing rate immediately post-fatigue was also greater
      on the affected side than less-affected side (-13.5 +/- 20 and 0.1 +/- 19%, p =
      0.04). Mean MU firing rates increased following the recovery period on the less
      affected side when compared to the affected side (19.3 +/- 17 and 0.5 +/- 20%,
      respectively, p = 0.03). MU action potential duration increased post-fatigue on
      both sides (10.3 +/- 1.2 to 11.2 +/- 1.3 ms on the affected side and 9.9 +/- 1.7
      to 11.2 +/- 1.9 ms on the less-affected side, p = 0.001 and p = 0.02,
      respectively), and changes in action potential duration tended to be smaller in
      subjects with greater impairment (p = 0.04). This study presents evidence of both
      central and peripheral fatigue at the MU level during isometric fatiguing
      contraction for the first time in stroke survivors. Together, these preliminary
      observations indicate that the response to an isometric fatiguing contraction
      differs between the affected and less-affected side post-stroke, and may suggest
      that central mechanisms observed here as changes in firing rate are the dominant
      processes leading to task failure on the affected side.

PMID- 29225575
TI  - Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1.
AB  - Activation of trace amine-associated receptor 1 (TAAR1) in endocrine pancreas is
      involved in weight regulation and glucose homeostasis. The purpose of this study
      was the identification and characterization of potential TAAR1 variants in
      patients with overweight/obesity and disturbed glucose homeostasis. Screening for
      TAAR1 variants was performed in 314 obese or overweight patients with impaired
      insulin secretion. The detected variants were functionally characterized
      concerning TAAR1 cell surface expression and signaling properties and their
      allele frequencies were determined in the population-based Study of Health in
      Pomerania (SHIP). Three heterozygous carriers of the single nucleotide missense
      variants p.Arg23Cys (R23C, rs8192618), p.Ser49Leu (S49L, rs140960896), and
      p.Ille171Leu (I171L, rs200795344) were detected in the patient cohort. While
      p.Ser49Leu and p.Ille171Leu were found in obese/overweight patients with slightly
      impaired glucose homeostasis, p.Arg23Cys was identified in a patient with a
      complete loss of insulin production. Functional in vitro characterization
      revealed a like wild-type function for I171L, partial loss of function for S49L
      and a complete loss of function for R23C. The frequency of the R23C variant in
      2018 non-diabetic control individuals aged 60 years and older in the general
      population-based SHIP cohort was lower than in the analyzed patient sample. Both
      variants are rare in the general population indicating a recent origin in the
      general gene pool and/or the consequence of pronounced purifying selection, in
      line with the obvious detrimental effect of the mutations. In conclusion, our
      study provides hints for the existence of naturally occurring TAAR1 variants with
      potential relevance for weight regulation and glucose homeostasis.

PMID- 29225576
TI  - Vitamin D Enhances Efficacy of Oral Nifedipine in Treating Preeclampsia with
      Severe Features: A Double Blinded, Placebo-Controlled and Randomized Clinical
      Trial.
AB  - Vitamin D (VD) has exhibited immunomodulatory role in the pathogenesis of
      preeclampsia. We hypothesize VD potentiate nifedipine treatment for preeclampsia
      by shortened the time to control blood pressure and prolong time before
      subsequent hypertensive crisis. We conduct a randomized trial of 683 primigravid
      women with preeclampsia, who were assigned to different treatment groups, either
      nifedipine+placebo or nifedipine+VD orally, by random after screening. Primary
      endpoints include time to control hypertension and time before another
      hypertensive crisis. Maternal adverse effects including nausea, vomiting, chest
      pain, mild headache, dizziness, maternal tachycardia, hypotension or shortness of
      breath, and neonatal parameters including birth weight and Apgar scores, as well
      as the minimum number of dosages needed to control hypertension were defined as
      secondary endpoints. Serum levels of cytokines tumor necrosis factor-alpha (TNF
      alpha) and interleukin-10 (IL-10) were also examined. There was a marked
      reduction of the time required to control hypertension and a significant
      lengthening (p = 0.013) of the time before a new hypertensive crisis in
      participants received nifedipine+VD treatments (41.8 +/- 18.3 min), in comparison
      with the nifedipine+placebo controls (61.1 +/- 15.9 min). In women treated with
      nifedipine+VD, the minimum number of dosages needed to control hypertension was
      also lower. With regard to adverse effects, no statistical difference was
      observed between the two treatment groups. Moreover, treatment with VD increased
      IL-10 and reduced TNF-alpha serum levels. VD possesses the potential of serving
      as a safe and effective adjuvant to oral nifedipine in treating women with
      preeclampsia against hypertension, possibly through the upregulation of IL-10 and
      the downregulation of TNF-alpha.

PMID- 29225577
TI  - If Channel as an Emerging Therapeutic Target for Cardiovascular Diseases: A
      Review of Current Evidence and Controversies.
AB  - In 2015, non-communicable diseases accounted for 39.5 million (70%) of the total
      56.4 million deaths that occurred globally, of which 17.7 million (45%) were due
      to cardiovascular diseases. An elevated heart rate is considered to be one of the
      independent predictors and markers of future cardiovascular diseases. A variety
      of experimental and epidemiological studies have found that atherosclerosis,
      heart failure, coronary artery disease, stroke, and arrhythmia are linked to
      elevated heart rate. Although there are established drugs to reduce the heart
      rate, these drugs have undesirable side effects. Hence, the development of new
      drugs that selectively inhibit the heart rate is considered necessary. In the
      search for such drugs, almost four decades ago the If channel, also known as the
      "funny channel," emerged as a novel site for the selective inhibition of heart
      rate. These If channels, with a mixed sodium and potassium inward current, have
      been identified in the sinoatrial node of the heart, which mediates the slow
      diastolic depolarization of the pacemaker of the spontaneous rhythmic cells. The
      hyperpolarization-activated cyclic nucleotide-gated (HCN) subfamily is primarily
      articulated in the heart and neurons that are encoded by a family of four genes
      (HCN1-4) and they identify the funny channel. Of these, HCN-4 is the principal
      protein in the sinoatrial node. Currently, funny channel inhibition is being
      targeted for the treatment and prevention of cardiovascular diseases such as
      atherosclerosis and stroke. A selective If channel inhibitor named ivabradine was
      discovered for clinical use in treating heart failure and coronary artery
      disease. However, inconsistencies regarding the clinical effects of ivabradine
      have been reported in the literature, suggesting the need for a rigorous analysis
      of the available evidence. The objective of this review is therefore to assess
      the current advances in targeting the If channel associated with ivabradine and
      related challenges.

PMID- 29225578
TI  - Curcumin Suppresses the Colon Cancer Proliferation by Inhibiting Wnt/beta-Catenin
      Pathways via miR-130a.
AB  - Curcumin exhibits anti-tumor effects in several cancers, including colorectal
      carcinoma (CRC), but the detailed mechanisms are still unclear. Here we studied
      the mechanisms underlying the anti-tumor effect of curcumin in colon cancer
      cells. SW480 cells were injected into mice to establish the xenograft tumor
      model, followed by evaluation of survival rate with the treatment of curcumin.
      The expression levels of beta-catenin, Axin and TCF4 were measured in the SW480
      cells in the absence or presence of curcumin. Moreover, miRNAs related to the
      curcumin treatment were also detected in vitro. Curcumin could suppress the
      growth of colon cancer cells in the mouse model. This anti-tumor activity of
      curcumin was exerted by inhibiting cell proliferation rather than promoting cell
      apoptosis. Further study suggested that curcumin inhibited cell proliferation by
      suppressing the Wnt/beta-catenin pathway. MiR-130a was down-regulated by curcumin
      treatment, and overexpressing miR-130a could abolish the anti-tumor activity of
      curcumin. Our study confirms that curcumin is able to inhibit colon cancer by
      suppressing the Wnt/beta-catenin pathways via miR-130a. MiR-130a may serve as a
      new target of curcumin for CRC treatment.

PMID- 29225580
TI  - Pulsatility of Lenticulostriate Arteries Assessed by 7 Tesla Flow MRI
      Measurement, Reproducibility, and Applicability to Aging Effect.
AB  - Characterization of flow properties in cerebral arteries with 1.5 and 3 Tesla MRI
      is usually limited to large cerebral arteries and difficult to evaluate in the
      small perforating arteries due to insufficient spatial resolution. In this study,
      we assessed the feasibility to measure blood flow waveforms in the small
      lenticulostriate arteries with 7 Tesla velocity-sensitive MRI. The middle
      cerebral artery was included as reference. Imaging was performed in five young
      and five old healthy volunteers. Flow was calculated by integrating time-varying
      velocity values over the vascular cross-section. MRI acquisitions were performed
      twice in each subject to determine reproducibility. From the flow waveforms, the
      pulsatility index and damping factor were deduced. Reproducibility values, in
      terms of the intraclass correlation coefficients, were found to be good to
      excellent. Measured pulsatility index of the lenticulostriate arteries
      significantly increased and damping factor significantly decreased with age. In
      conclusion, we demonstrate that blood flow through the lenticostriate arteries
      can be precisely measured using 7 Tesla MRI and reveal effects of arterial
      stiffness due to aging. These findings hold promise to provide relevant insights
      into the pathologies involving perforating cerebral arteries.

PMID- 29225579
TI  - Regulation of Tissue Growth by the Mammalian Hippo Signaling Pathway.
AB  - The integrative control of diverse biological processes such as proliferation,
      differentiation, apoptosis and metabolism is essential to maintain cellular and
      tissue homeostasis. Disruption of these underlie the development of many disease
      states including cancer and diabetes, as well as many of the complications that
      arise as a consequence of aging. These biological outputs are governed by many
      cellular signaling networks that function independently, and in concert, to
      convert changes in hormonal, mechanical and metabolic stimuli into alterations in
      gene expression. First identified in Drosophila melanogaster as a powerful
      mediator of cell division and apoptosis, the Hippo signaling pathway is a highly
      conserved regulator of mammalian organ size and functional capacity in both
      healthy and diseased tissues. Recent studies have implicated the pathway as an
      effector of diverse physiological cues demonstrating an essential role for the
      Hippo pathway as an integrative component of cellular homeostasis. In this
      review, we will: (a) outline the critical signaling elements that constitute the
      mammalian Hippo pathway, and how they function to regulate Hippo pathway
      dependent gene expression and tissue growth, (b) discuss evidence that shows this
      pathway functions as an effector of diverse physiological stimuli and

PMID- 29225581
TI  - Protective Effect of Unacylated Ghrelin on Compression-Induced Skeletal Muscle
      Injury Mediated by SIRT1-Signaling.
AB  - Unacylated ghrelin, the predominant form of circulating ghrelin, protects
      myotubes from cell death, which is a known attribute of pressure ulcers. In this
      study, we investigated whether unacylated ghrelin protects skeletal muscle from
      pressure-induced deep tissue injury by abolishing necroptosis and apoptosis
      signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult
      Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or
      without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles
      with 100 mmHg static pressure applied over the mid-tibialis region of the right
      limb whereas the left uncompressed limb served as the intra-animal control.
      Muscle tissues underneath the compression region, and at the similar region of
      the opposite uncompressed limb, were collected for analysis. Unacylated ghrelin
      attenuated the compression-induced muscle pathohistological alterations including
      rounding contour of myofibers, extensive nucleus accumulation in the interstitial
      space, and increased interstitial space. Unacylated ghrelin abolished the
      increase in necroptosis proteins including RIP1 and RIP3 and attenuated the
      elevation of apoptotic proteins including p53, Bax, and AIF in the compressed
      muscle. Furthermore, unacylated ghrelin opposed the compression-induced
      phosphorylation and acetylation of p65 subunit of NF-kB. The anti-apoptotic
      effect of unacylated ghrelin was shown by a decrease in apoptotic DNA
      fragmentation and terminal dUTP nick-end labeling index in the compressed muscle.
      The protective effects of unacylated ghrelin vanished when co-treated with EX527.
      Our findings demonstrated that unacylated ghrelin protected skeletal muscle from
      compression-induced injury. The myoprotective effects of unacylated ghrelin on
      pressure-induced tissue injury were associated with SIRT1 signaling.

PMID- 29225583
TI  - Item Response Patterns on the Patient Health Questionnaire-8 in a Nationally
      Representative Sample of US Adults.
AB  - Recent studies have shown that item responses on the Center for Epidemiologic
      Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological
      Distress (K6) exhibit the same characteristic item response patterns among the
      general population. However, the distributional patterns of responses on the
      Patient Health Questionnaire-8 (PHQ-8) among the general population have not been
      adequately studied. Thus, we conducted a pattern analysis of PHQ-8 item responses
      among US adults. Data (18,446 individuals) were obtained from the 2015 Behavioral
      Risk Factor Surveillance Survey (BRFSS). Item responses on the BRFSS version of
      the PHQ-8 were scored using the number of days response set and then converted to
      the original 4-point scale. The patterns of item responses were analyzed through
      graphical analysis. Lines of item responses scored using the number of days
      response set showed the same pattern among the eight items, characterized by
      crossing at a single point between "0 days" and "1 day," and parallel fluctuation
      from "1 day" to "14 days" on a semi-logarithmic scale. Lines of item responses
      converted to the 4-point scale also showed the same characteristic pattern among
      the eight items. The present results demonstrate that the item responses on the
      PHQ-8 show the same characteristic patterns among items, consistent with the CES
      D and the K6.

PMID- 29225582
TI  - Significant Need for a French Network of Expert Centers Enabling a Better
      Characterization and Management of Treatment-Resistant Depression (Fondation
      FondaMental).
AB  - Background: Major depression is characterized by (i) a high lifetime prevalence
      of 16-17% in the general population; (ii) a high frequency of treatment
      resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a
      negative impact on the general functioning and quality of life; and (v) a high
      level of comorbidity with various psychiatric and non-psychiatric disorders, high
      occurrence of completed suicide, significant burden along with the personal,
      societal, and economic costs. In this context, there is an important need for the
      development of a network of expert centers for treatment-resistant depression
      (TRD), as performed under the leadership of the Fondation FondaMental. Methods:
      The principal mission of this national network is to establish a genuine
      prevention, screening, and diagnosis policy for TRD to offer a systematic,
      comprehensive, longitudinal, and multidimensional evaluation of cases. A shared
      electronic medical file is used referring to a common exhaustive and standardized
      set of assessment tools exploring psychiatric, non-psychiatric, metabolic,
      biological, and cognitive dimensions of TRD. This is paralleled by a medico
      economic evaluation to examine the global economic burden of the disease and
      related health-care resource utilization. In addition, an integrated biobank has
      been built by the collection of serum and DNA samples for the measurement of
      several biomarkers that could further be associated with the treatment resistance
      in the recruited depressed patients. A French observational long-term follow-up
      cohort study is currently in progress enabling the extensive assessment of
      resistant depressed patients. In those unresponsive cases, each expert center
      proposes relevant therapeutic options that are classically aligned to the
      international guidelines referring to recognized scientific societies.
      Discussion: This approach is expected to improve the overall clinical assessments
      and to provide evidence-based information to those clinicians most closely
      involved in the management of TRD thereby facilitating treatment decisions and
      choice in everyday clinical practice. This could contribute to significantly
      improve the poor prognosis, the relapsing course, daily functioning and heavy
      burden of TRD. Moreover, the newly created French network of expert centers for
      TRD will be particularly helpful for a better characterization of
      sociodemographic, clinical, neuropsychological, and biological markers of
      treatment resistance required for the further development of personalized
      therapeutic strategies in TRD.

PMID- 29225584
TI  - Prevalence Rates of the Incubus Phenomenon: A Systematic Review and Meta
      Analysis.
AB  - Background: The incubus phenomenon is a paroxysmal sleep-related disorder
      characterized by compound hallucinations experienced during brief phases of
      (apparent) wakefulness. The condition has an almost stereotypical presentation,
      characterized by a hallucinated being that exerts pressure on the thorax,
      meanwhile carrying out aggressive and/or sexual acts. It tends to be accompanied
      by sleep paralysis, anxiety, vegetative symptoms, and feelings of suffocation.
      Its prevalence rate is unknown since, in prior analyses, cases of recurrent
      isolated sleep paralysis with/without an incubus phenomenon have been pooled
      together. This is unfortunate, since the incubus phenomenon has a much greater
      clinical relevance than isolated sleep paralysis. Methods: PubMed, Embase, and
      PsycINFO were searched for prevalence studies of the incubus phenomenon, and a
      meta-analysis was performed. Results: Of the 1,437 unique records, 13 met the
      inclusion criteria, reporting on 14 (k) independent prevalence estimates (total N
      = 6,079). The pooled lifetime prevalence rate of the incubus phenomenon was 0.19
      [95% confidence interval (CI) = 0.14-0.25, k = 14, N = 6,079] with heterogeneous
      estimates over different samples. In selected samples (e.g., patients with a
      psychiatric disorder, refugees, and students), prevalence rates were nearly four
      times higher (0.41, 95% CI = 0.25-0.56, k = 4, n = 1,275) than in the random
      samples (0.11, 95% CI = 0.08-0.14, k = 10, n = 4,804). This difference was
      significant (P < 0.001). Conclusion: This review and meta-analysis yielded a
      lifetime prevalence of the incubus phenomenon in the general population of 0.11
      and, in selected samples, of 0.41. This is slightly higher than the prevalence
      rates in previous analyses that included cases of recurrent isolated sleep
      paralysis without an incubus phenomenon. Based on the condition's robust clinical
      presentation and the relatively high prevalence rates, we advocate inclusion of
      the incubus phenomenon as a diagnostic category in major classifications such as
      the International Classification of Diseases and Related Health Problems and the
      Diagnostic and Statistical Manual of Mental Disorders. Recommendations are also
      made for clinical practice and future research.

PMID- 29225585
TI  - Complement Coercion: The Joint Effects of Type and Typicality.
AB  - Complement coercion (begin a book ->reading) involves a type clash between an
      event-selecting verb and an entity-denoting object, triggering a covert event
      (reading). Two main factors involved in complement coercion have been
      investigated: the semantic type of the object (event vs. entity), and the
      typicality of the covert event (the author began a book ->writing). In previous
      research, reading times have been measured at the object. However, the influence
      of the typicality of the subject-object combination on processing an aspectual
      verb such as begin has not been studied. Using a self-paced reading study, we
      manipulated semantic type and subject-object typicality, exploiting German word
      order to measure reading times at the aspectual verb. These variables interacted
      at the target verb. We conclude that both type and typicality probabilistically
      guide expectations about upcoming input. These results are compatible with an
      expectation-based view of complement coercion and language comprehension more
      generally in which there is rapid interaction between what is typically viewed as
      linguistic knowledge, and what is typically viewed as domain general knowledge
      about how the world works.

PMID- 29225586
TI  - Extending the Cooperative Phenotype: Assessing the Stability of Cooperation
      across Countries.
AB  - This paper studies whether individual cooperation is stable across settings and
      over time. Involving more than 7,000 subjects on two different continents, this
      study documents positive correlation in cooperative behavior across economic
      games in Norway, Sweden, Austria, and the United States. The game measures also
      correlate with a tendency to make deontological judgments in moral dilemmas, and
      display of general trust toward strangers. Using time-variation in the data, we
      test whether temporal stability of behavior is similar in the United States and
      Norway, and find similar stability estimates for both the American and Norwegian
      samples. The findings here provide further evidence of the existence of a stable
      behavioral inclination toward prosociality - a "cooperative phenotype," as it has
      recently been termed. Also in line with previous research, we find that
      punishment and cooperation seem to be uncorrelated.

PMID- 29225587
TI  - Psychological Availability between Self-Initiated Expatriates and Host Country
      Nationals during Their Adjustment: The Moderating Role of Supportive Supervisor
      Relations.
AB  - This research examined the role of psychological availability as a means of
      psychological engagement between self-initiated expatriates (SIEs) and their host
      country nationals (HCNs) colleagues during their work and interaction adjustment.
      To reveal this process, this study presented the concept of psychological
      availability, which refers to an individual's belief that they are physically,
      cognitively, and emotionally ready or confident to engage the self with their
      colleagues, as a mediator between proactive personality and adjustment. Also, it
      investigated the relationship between proactive personality and psychological
      availability and how it was moderated by supportive supervisor relations. We
      hypothesized, this relationship would be weakened/strengthened when SIEs and HCNs
      received low/high level of support from their supervisor. This study was
      conducted as a quantitative study, data was used from 342 SIEs and 342 HCNs
      working in mainland China. Our finding supported the hypothesis that
      psychological availability mediated the relationship between proactive
      personality and their adjustment to an international work environment; in
      addition, the relationship between proactive personality and psychological
      availability would be stronger when the level of superiors relations support is
      high between SIEs and HCNs. This study demonstrated the value of proactive
      personality as an antecedent effect and supportive supervisor relations as a
      moderating effect, and investigated how these factors can lead to a sense of
      psychological availability and boost psychological engagement between SIEs and
      HCNs in order to improve the adjustment between them.

PMID- 29225588
TI  - Income Inequality and Happiness: An Inverted U-Shaped Curve.
AB  - Numerous studies agree that income inequality, rather than absolute income, is an
      important predictor of happiness. However, its specific role has been
      controversial. We argue that income inequality and happiness should exhibit an
      inverted U-shaped relationship due to the dynamic competing process between two
      effects: when income inequality is relatively low, the signal effect will be the
      dominating factor, in which individuals feel happy because they consider income
      inequality as a signal of social mobility and expect upward mobility; however, if
      income inequality level increases beyond a critical point, the jealousy effect
      will become the dominating factor, in which individuals tend to be unhappy
      because they are disillusioned about the prospect of upward mobility and jealous
      of their wealthier peers. This hypothesis is tested in a longitudinal dataset on
      the United States and a cross-national dataset on several European countries. In
      both datasets, the Gini coefficient (a common index of a society's income
      inequality) and its quadratic term were significant predictors of personal
      happiness. Further examinations of the quadratic relationships showed that the
      signal effect was only presented in the European data, while the jealousy effect
      was presented in both datasets. These findings shed new light on our
      understanding of the relationship between income inequality and personal
      happiness.

PMID- 29225589
TI  - State of the Art of Interpersonal Physiology in Psychotherapy: A Systematic
      Review.
AB  - Introduction: The fast expanding field of Interpersonal Physiology (IP) focuses
      on the study of co-ordination or synchronization dynamics between the
      physiological activities of two, or more, individuals. IP has been associated
      with various relational features (e.g., empathy, attachment security, rapport,
      closeness...) that overlap with desirable characteristics of clinical
      relationships, suggesting that the relevant studies might provide objective,
      economical, and theory-free techniques to investigate the clinical process. The
      goal of the present work is to systematically retrieve and review the literature
      on IP in the field of psychotherapy and psychological intervention, in order to
      consolidate the knowledge of this research domain, highlight its critical issues,
      and delineate possible developments. Method: Following the guidelines by Okoli
      and Schabram (2010), a systematic literature search was performed in Scopus, Web
      of Science, PsycINFO, and PubMed databases by means of multiple keyword
      combinations; the results were integrated with references to the retrieved
      articles' bibliography as well as to other published reviews on IP. Results: All
      the retrieved documents reported clinical interactions that are characterized, at
      least partially, by IP phenomena. They appear to use fragmented and sometimes
      ambiguous terminology and show a lack of both specific theory-informed hypotheses
      and sound analytical procedures. Conclusion: Although the psychological nature of
      IP and its role in the clinical relationship are still mostly unknown, the
      potential value of a physiology-based measure of implicit exchanges in
      psychotherapy drives an acceleration in this research field. On the basis of the
      highlighted critical issues, possible future directions for clinical IP
      researchers are discussed.

PMID- 29225590
TI  - N170 Reveals the Categorical Perception Effect of Emotional Valence.
AB  - As an important attribute of facial expression, emotional valence has been well
      explored, but its processing mechanisms remain ambiguous. Investigating the
      categorical perception (CP) of emotional valence might help uncover the objective
      basis of the subjective dichotomy of emotional valence and identify the stage at
      which this processing of valence information might occur. A judgment task was
      used in the current study with stimuli from the within- or between-category
      condition, in which participants were required to decide whether two presented
      faces showed the same emotion. The results of the behavioral experiment revealed
      a significant CP effect of emotional valence, with faster RTs and greater
      accuracy for the between- than for the within-category stimuli. In the ERP
      experiment, the N170 (peaking at approximately 150-170 ms) was found to reflect
      the CP effect of emotional valence, with a larger amplitude for the within- than
      for the between-category condition. In contrast, the P1 component (peaking at
      approximately 100-130 ms) was insensitive to the CP effect of emotional valence.
      These results reveal the existence of the CP of emotional valence and indicate
      that the N170 is its earliest electrophysiological index. Therefore, the
      categorization of emotional valence not only has an objective neural basis but
      occurs at a relatively early stage of processing.

PMID- 29225591
TI  - Incidence of Peripheral Arterial Disease and Its Association with Pulse Pressure:
      A Prospective Cohort Study.
AB  - Background: The association of pulse pressure and peripheral arterial disease
      (PAD) has seldom been examined using a prospective design. This study aimed to
      investigate the association of pulse pressure with PAD incidence in an elderly
      general population. Methods: We utilized data from a cohort conducted in Beijing
      with additionally 2-year follow-up time. PAD was defined as an ankle brachial
      index value <0.9 in either leg. Cox proportional hazard regression model was used
      to quantify the magnitude of pulse pressure on PAD incidence. Results: During a 2
      year follow-up time, 357 of 4,201 (8.5%) participants developed PAD with 105
      (6.9%) men and 252 (9.4%) women, respectively. After adjusting for baseline age,
      sex, body mass index, hypertension, diabetes, total cholesterol, and high-density
      lipoprotein cholesterol, and smoking, the hazard ratio and 95% confidence
      interval for people with pulse pressure greater than 60 mmHg was 2.20 (1.53,
      3.15) compared with those whose pulse pressure was less than 40 mmHg. A linear
      trend was observed for the association of pulse pressure with PAD. Conclusion:
      Higher pulse pressure was associated with higher PAD incidence.

PMID- 29225592
TI  - Bacterial Succession on Sinking Particles in the Ocean's Interior.
AB  - Sinking particles formed in the photic zone and moving vertically through the
      water column are a main mechanism for nutrient transport to the deep ocean, and a
      key component of the biological carbon pump. The particles appear to be processed
      by a microbial community substantially different from the surrounding waters.
      Single cell genomics and metagenomics were employed to describe the succession of
      dominant bacterial groups during particle processing. Sinking particles were
      extracted from sediment traps at Station Aloha in the North Pacific Subtropical
      Gyre (NPSG) during two different trap deployments conducted in July and August
      2012. The microbial communities in poisoned vs. live sediment traps differed
      significantly from one another, consistent with prior observations by Fontanez et
      al. (2015). Partial genomes from these communities were sequenced from cells
      belonging to the genus Arcobacter (commensalists potentially associated with
      protists such as Radiolaria), and Vibrio campbellii (a group previously reported
      to be associated with crustacea). These bacteria were found in the particle
      associated communities at specific depths in both trap deployments, presumably
      due to their specific host-associations. Partial genomes were also sequenced from
      cells belonging to Idiomarina and Kangiella that were enriched in live traps over
      a broad depth range, that represented a motile copiotroph and a putatively non
      motile algicidal saprophyte, respectively. Planktonic bacterial cells most likely
      caught in the wake of the particles belonging to Actinomarina and the SAR11 clade
      were also sequenced. Our results suggest that similar groups of eukaryote
      associated bacteria are consistently found on sinking particles at different
      times, and that particle remineralization involves specific, reproducible
      bacterial succession events in oligotrophic ocean waters.

PMID- 29225593
TI  - Diverse Cone-Snail Species Harbor Closely Related Streptomyces Species with
      Conserved Chemical and Genetic Profiles, Including Polycyclic Tetramic Acid
      Macrolactams.
AB  - Streptomyces are Gram-positive bacteria that occupy diverse ecological niches
      including host-associations with animals and plants. Members of this genus are
      known for their overwhelming repertoire of natural products, which has been
      exploited for almost a century as a source of medicines and agrochemicals.
      Notwithstanding intense scientific and commercial interest in Streptomyces
      natural products, surprisingly little is known of the intra- and/or inter-species
      ecological roles played by these metabolites. In this report we describe the
      chemical structures, biological properties, and biosynthetic relationships
      between natural products produced by Streptomyces isolated from internal tissues
      of predatory Conus snails, collected from the Great Barrier Reef, Australia.
      Using chromatographic, spectroscopic and bioassays methodology, we demonstrate
      that Streptomyces isolated from five different Conus species produce identical
      chemical and antifungal profiles - comprising a suite of polycyclic tetramic acid
      macrolactams (PTMs). To investigate possible ecological (and evolutionary)
      relationships we used genome analyses to reveal a close taxonomic relationship
      with other sponge-derived and free-living PTM producing Streptomyces (i.e.,
      Streptomyces albus). In-depth phylogenomic analysis of PTM biosynthetic gene
      clusters indicated PTM structure diversity was governed by a small repertoire of
      genetic elements, including discrete gene acquisition events involving
      dehydrogenases. Overall, our study shows a Streptomyces-Conus ecological
      relationship that is concomitant with specific PTM chemical profiles. We provide
      an evolutionary framework to explain this relationship, driven by anti-fungal
      properties that protect Conus snails from fungal pathogens.

PMID- 29225594
TI  - Overexpression of OsCIPK30 Enhances Plant Tolerance to Rice stripe virus.
AB  - Rice stripe virus (RSV) causes a severe disease in Oryza sativa (rice) in many
      Eastern Asian countries. The NS3 protein of RSV is a viral suppressor of RNA
      silencing, but plant host factors interacting with NS3 have not been reported
      yet. Here, we present evidence that expression of RSV NS3 in Arabidopsis thaliana
      causes developmental abnormalities. Through yeast two-hybrid screening and a
      luciferase complementation imaging assay, we demonstrate that RSV NS3 interacted
      with OsCIPK30, a CBL (calcineurin B-like proteins)-interaction protein kinase
      protein. Furthermore, OsCIPK30 was overexpressed to investigate the function of
      OsCIPK30 in rice. Our investigation showed that overexpression of OsCIPK30 in
      rice could delay the RSV symptoms and show milder RSV symptoms. In addition, the
      expression of pathogenesis-related genes was increased in OsCIPK30 transgenic
      rice. These results suggest that overexpression of OsCIPK30 positively regulates
      pathogenesis-related genes to enhance the tolerance to RSV in rice. Our findings
      provide new insight into the molecular mechanism underlying resistance to RSV
      disease.

PMID- 29225595
TI  - Characteristics of and Virulence Factors Associated with Biofilm Formation in
      Clinical Enterococcus faecalis Isolates in China.
AB  - Enterococcus faecalis biofilm traits and distribution characteristics in China
      have not been clarified. This study aimed to determine the prevalence and
      characteristics of E. faecalis biofilm formation in a sample of clinical isolates
      and to explore the virulence factors associated with biofilm formation in those
      isolates. A total of 265 E. faecalis isolates were collected from patients in
      Shenzhen, China. Virulence genes were detected within the genomes of the microbes
      by polymerase chain reaction. The isolates were subjected to multilocus sequence
      typing (MLST) based on housekeeping genes. Biofilms were detected by crystal
      violet staining. The expression levels of the clinical E. faecalis isolates'
      genes were determined by quantitative real-time polymerase chain reaction. The
      prevalence of biofilm formation among E. faecalis clinical isolates was 47.2%.
      MLST yielded 44 different sequence types (STs). The main STs were ST16 and ST179;
      the ST16 isolates were more likely to form strong or medium biofilm than the
      ST179 isolates (p < 0.001). Strong or medium biofilm formation was more common in
      linezolid-resistant isolates than in linezolid-sensitive isolates (p = 0.001).
      Biofilm formation was more frequently detected in enterococcal surface protein
      (esp+), surface aggregating protein (asa1+), cytolysin A (cylA+), or aggregation
      substance (agg+) positive isolates than in isolates that were negative (-) for
      these virulence factors. Multivariate regression analysis indicated that cylA
      [odds ratio (OR) 4.083, p < 0.001] was a risk factor for weak biofilm formation,
      and that esp (OR 8.207, p < 0.001) was a risk factor for strong or medium biofilm
      formation. The expression of cylA was raised (4.02 to 6.00-fold) in weak biofilm
      isolates compared to the biofilm-negative isolates, and the expression of esp was
      greatly elevated (11.39 to 134.08-fold) in strong biofilm isolates compared to
      biofilm-negative isolates. In conclusion, the ST16 classification and linezolid
      resistance were positively associated with strong/medium biofilm formation in
      clinical E. faecalis isolates. cylA was associated with weak biofilm formation,
      and esp was only associated with strong or medium biofilm formation of the
      clinical E. faecalis isolates.

PMID- 29225596
TI  - IL-15 Enhances Activation and IGF-1 Production of Dendritic Epidermal T Cells to
      Promote Wound Healing in Diabetic Mice.
AB  - Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs)
      contribute to abnormal diabetic wound healing. IL-15 plays important roles in
      survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15
      has been reported as an important mechanism for abnormal DETC homeostasis in
      streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired
      diabetic wound healing remains unknown. Here, we found that, through rescuing the
      insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and
      thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL
      15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and
      IGF-1 were positively correlated in wounded epidermis. Together, our data
      indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic
      wound repair, suggesting IL-15 as a potential therapeutic agent for managing
      diabetic wound healing.

PMID- 29225599
TI  - Promoter Specificity and Efficacy in Conditional and Inducible Transgenic
      Targeting of Lung Macrophages.
AB  - Conditional and inducible Cre-loxP systems are used to target gene deletion to
      specific cell lineages and tissues through promoter-restricted expression of the
      bacterial DNA recombinase, Cre. Although Cre-loxP systems are widely used to
      target gene deletion in lung macrophages, limited data are published on the
      specificity and efficiency of "macrophage targeting" Cre lines. Using R26
      stopfl/fl-TdTomato and tetOn-GFP reporter lines, we assessed the specificity and
      efficiency of four commercially available Cre driver lines that are often
      considered "macrophage specific." We evaluated two conditional (Csf1r-Cre and
      LysM-Cre) and two inducible [CX3CR1-estrogen receptor-Cre (ERCre) and CD68-rtTA]
      lines. We assessed Cre activation in six resident lung myeloid populations, as
      well as activation in lung leukocytes, lung epithelial and endothelial cells,
      peripheral blood leukocytes, and tissue macrophages of the spleen, bone marrow,
      and peritoneal cavity. Although Csf1r-Cre and LysM-Cre target resident alveolar
      macrophages (ResAM) and interstitial macrophages (IM) with high efficiency,
      neither line is specific for macrophages. Csf1r-Cre targets all leukocyte
      populations, while LysM-Cre targets dendritic cell, neutrophils, monocytes, and a
      quarter of lung epithelial cells. CX3CR1-ERCre and CD68-rtTA both target IM, but
      do not target ResAM. Further, although neither line is specific for macrophages,
      a pulse-wait administration of tamoxifen or doxycycline can be used to
      significantly improve IM specificity in these inducible lines. In summary, while
      Cre-loxP remains a powerful tool to study macrophage function, numerous pitfalls
      exist. Herein, we document strengths and weaknesses of Csf1r-Cre, LysM-Cre,
      CX3CR1-ERCre, and CD68-rtTA systems for targeting specific macrophage populations
      in the lungs and provide data that will aid investigators in selecting the proper
      strain.

PMID- 29225597
TI  - Tregs: Where We Are and What Comes Next?
AB  - Regulatory T cells are usually recognized as a specialized subset of CD4+ T cells
      functioning in establishment and maintenance of immune tolerance. Meanwhile,
      there is emerging evidence that regulatory T cells (Tregs) are also present in
      various non-lymphoid tissues, and that they have unique phenotypes credited with
      activities distinct from regulatory function. Their development and function have
      been described in plenty of manuscripts in the past two decades. However, with
      the deepening of research in recent years, emerging evidence revealed some novel
      mechanisms about how Tregs exert their activities. First, we discuss the
      expanding family of regulatory lymphocytes briefly and then, try to interpret how
      fork-head box P3 (Foxp3), a master regulator of the regulatory pathway in the
      development and function of regulatory T cells, functions. Subsequently, another
      part of our focus is varieties of tissue Tregs. Next, we primarily discuss recent
      research on how Tregs work and their faceted functions in terms of soluble
      mediators, functional proteins, and inhibitory receptors. In particular, unless
      otherwise noted, the term "Treg" is used here to refer specially to the
      "CD4+CD25+Foxp3+" regulatory cells.

PMID- 29225598
TI  - Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of
      Hemophilia A.
AB  - Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic
      disorder that is primarily treated with intravenous replacement therapy. Despite
      a variety of factor VIII protein formulations available, the risk of developing
      anti-dug antibodies ("inhibitors") remains. Overall, 20-30% of patients with
      severe disease develop inhibitors. Current clinical immune tolerance induction
      protocols to eliminate inhibitors are not effective in all patients, and there
      are no prophylactic protocols to prevent the immune response. New experimental
      therapies, such as gene and cell therapies, show promising results in pre
      clinical studies in animal models of hemophilia. Examples include hepatic gene
      transfer with viral vectors, genetically engineered regulatory T cells (Treg), in
      vivo Treg induction using immune modulatory drugs, and maternal antigen transfer.
      Furthermore, an oral tolerance protocol is being developed based on transgenic
      lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs.
      Hopefully, some of these innovative approaches will reduce the risk of and/or
      more effectively eliminate inhibitor formation in future treatment of hemophilia
      A.

PMID- 29225600
TI  - Hypoxic Stress-Induced Tumor and Immune Plasticity, Suppression, and Impact on
      Tumor Heterogeneity.
AB  - The microenvironment of a developing tumor is composed of proliferating cancer
      cells, blood vessels, stromal cells, infiltrating inflammatory cells, and a
      variety of associated tissue cells. The crosstalk between stromal cells and
      malignant cells within this environment crucially determines the fate of tumor
      progression, its hostility, and heterogeneity. It is widely accepted that hypoxic
      stresses occur in most solid tumors. Moreover, cancer cells found within hypoxic
      regions are presumed to represent the most aggressive and therapy-resistant
      fractions of the tumor. Here, we review evidence that hypoxia regulates cell
      plasticity, resistance to cell-mediated cytotoxicity, and immune suppression.
      Exposure to hypoxia occurs as a consequence of insufficient blood supply. Hypoxic
      cells activate a number of adaptive responses coordinated by various cellular
      pathways. Accumulating data also suggest that hypoxic stress in the tumor
      microenvironment promotes tumor escape mechanisms through the emergence of immune
      resistant tumor variants and immune suppression. Thus, solid tumors seem to build
      up a hostile hypoxic microenvironment that hampers cell-mediated immunity and
      dampen the efficacy of the immune response.

PMID- 29225601
TI  - Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and
      Their Extracellular Vesicles: Are We Still Learning?
AB  - Mesenchymal stromal cells (MSC) have been used to treat a broad range of disease
      indications such as acute and chronic inflammatory disorders, autoimmune
      diseases, and transplant rejection due to their potent immunosuppressive/anti
      inflammatory properties. The breadth of their usage is due in no small part to
      the vast quantity of published studies showing their ability to modulate multiple
      immune cell types of both the innate and adaptive immune response. While patient
      derived (autologous) MSC may be the safer choice in terms of avoiding unwanted
      immune responses, factors including donor comorbidities may preclude these cells
      from use. In these situations, allogeneic MSC derived from genetically unrelated
      individuals must be used. While allogeneic MSC were initially believed to be
      immune-privileged, substantial evidence now exists to prove otherwise with
      multiple studies documenting specific cellular and humoral immune responses
      against donor antigens following administration of these cells. In this article,
      we will review recent published studies using non-manipulated, inflammatory
      molecule-activated (licensed) and differentiated allogeneic MSC, as well as MSC
      extracellular vesicles focusing on the immune responses to these cells and
      whether or not such responses have an impact on allogeneic MSC-mediated safety
      and efficacy.

PMID- 29225602
TI  - Sphingosine-1-Phosphate Promotes the Persistence of Activated CD4 T Cells in
      Inflamed Sites.
AB  - Inflammation can be protective or pathogenic depending on context and timeframe.
      Acute inflammation, including the accumulation of CD4 T cells, accompanies
      protective immune responses to pathogens, but the presence of activated CD4 T
      cells at sites of inflammation is associated with chronic inflammatory disease.
      While significant progress has been made in understanding the migration of CD4 T
      cells into inflamed sites, the signals that lead to their persistence are poorly
      characterized. Using a murine ear model of acute inflammation and intravital two
      photon imaging, we have dissected the signals that mediate CD4 T cell
      persistence. We report the unexpected finding that the bioactive lipid,
      sphingosine-1-phosphate (S1P), is both necessary and sufficient for the
      persistence of activated CD4 T cells at peripheral tissues in acute inflammation.
      S1P mediated the enhanced motility of CD4 T cells at inflamed tissues but did not
      affect their migration to the downstream draining lymph node. We found that
      sphingosine kinase-1, which regulates S1P production is increased at inflamed
      sites in mice and in patients with the chronic inflammatory disease, rheumatoid
      arthritis. Together, these data suggest that S1P, or its regulators, may be key
      targets to promote or disrupt accumulation of CD4 T cells at inflamed tissues.

PMID- 29225603
TI  - Regulatory T Cells Suppress Inflammation and Blistering in Pemphigoid Diseases.
AB  - Regulatory T cells (Tregs) are well known for their modulatory functions in
      adaptive immunity. Through regulation of T cell functions, Tregs have also been
      demonstrated to indirectly curb myeloid cell-driven inflammation. However, direct
      effects of Tregs on myeloid cell functions are insufficiently characterized,
      especially in the context of myeloid cell-mediated diseases, such as pemphigoid
      diseases (PDs). PDs are caused by autoantibodies targeting structural proteins of
      the skin. Autoantibody binding triggers myeloid cell activation through specific
      activation of Fc gamma receptors, leading to skin inflammation and subepidermal
      blistering. Here, we used mouse models to address the potential contribution of
      Tregs to PD pathogenesis in vivo. Depletion of Tregs induced excessive
      inflammation and blistering both clinically and histologically in two different
      PD mouse models. Of note, in the skin of Treg-depleted mice with PD, we detected
      increased expression of different cytokines, including Th2-specific IL-4, IL-10,
      and IL-13 as well as pro-inflammatory Th1 cytokine IFN-gamma and the T cell
      chemoattractant CXCL-9. We next aimed to determine whether Tregs alter the
      migratory behavior of myeloid cells, dampen immune complex (IC)-induced myeloid
      cell activation, or both. In vitro experiments demonstrated that co-incubation of
      IC-activated myeloid cells with Tregs had no impact on the release of reactive
      oxygen species (ROS) but downregulated beta2 integrin expression. Hence, Tregs
      mitigate PD by altering the migratory capabilities of myeloid cells rather than
      their release of ROS. Modulating cytokine expression by administering an excess
      of IL-10 or blocking IFN-gamma may be used in clinical translation of these
      findings.

PMID- 29225604
TI  - Transcriptional Regulation of T-Cell Lipid Metabolism: Implications for Plasma
      Membrane Lipid Rafts and T-Cell Function.
AB  - It is well established that cholesterol and glycosphingolipids are enriched in
      the plasma membrane (PM) and form signaling platforms called lipid rafts,
      essential for T-cell activation and function. Moreover, changes in PM lipid
      composition affect the biophysical properties of lipid rafts and have a role in
      defining functional T-cell phenotypes. Here, we review the role of
      transcriptional regulators of lipid metabolism including liver X receptors
      alpha/beta, peroxisome proliferator-activated receptor gamma, estrogen receptors
      alpha/beta (ERalpha/beta), and sterol regulatory element-binding proteins in T
      cells. These receptors lie at the interface between lipid metabolism and immune
      cell function and are endogenously activated by lipids and/or hormones.
      Importantly, they regulate cellular cholesterol, fatty acid, glycosphingolipid,
      and phospholipid levels but are also known to modulate a broad spectrum of immune
      responses. The current evidence supporting a role for lipid metabolism pathways
      in controlling immune cell activation by influencing PM lipid raft composition in
      health and disease, and the potential for targeting lipid biosynthesis pathways
      to control unwanted T-cell activation in autoimmunity is reviewed.

PMID- 29225605
TI  - The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other
      Pediatric Solid Tumors.
AB  - Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in
      an impressive success rate exemplified by a few high profile cases. However, this
      momentum is not readily extended to pediatric immunotherapy, and it is not for
      lack of trying. Though reasons for the slower advance are not apparent, some
      issues can be raised. Pediatric cancer patients represent a distinct demographic
      group whose immune system is inherently different from that of mature adults.
      Treating pediatric patients with immunotherapy designed for adults may not yield
      objective clinical responses. Here, we will present an update on adoptive T-cell
      and natural killer-cell therapies for neuroblastoma and other childhood solid
      tumors. Additionally, we will delineate key differences between human
      fetal/neonatal and adult immune systems. We hope this will generate interests
      leading to the discussion of potential future directions for improving adoptive
      cancer immunotherapy for children.

PMID- 29225606
TI  - Epstein-Barr Virus-Specific Immune Control by Innate Lymphocytes.
AB  - Epstein-Barr virus (EBV) is a potent B cell transforming pathogen in humans. In
      most persistently EBV-infected individuals, potent cytotoxic lymphocyte responses
      prevent EBV-associated pathologies. In addition to comprehensive adaptive T cell
      responses, several innate lymphocyte populations seem to target different stages
      of EBV infection and are compromised in primary immunodeficiencies that render
      individuals susceptible to symptomatic EBV infection. In this mini-review, I will
      highlight the functions of natural killer, gammadelta T cells, and natural killer
      T cells during innate immune responses to EBV. These innate lymphocyte
      populations seem to restrict both lytic replication and transforming latent EBV
      antigen expression. The mechanisms underlying the recognition of these different
      EBV infection programs by the respective innate lymphocytes are just starting to
      become unraveled, but will provide immunotherapeutic strategies to target
      pathologies that are associated with the different EBV infection programs.

PMID- 29225607
TI  - Alternative Splicing of CIPK3 Results in Distinct Target Selection to Propagate
      ABA Signaling in Arabidopsis.
AB  - Calcium (Ca2+) signaling is pivotal in transmission of information in the cell.
      Various Ca2+ sensing molecules work to sense and relay the encrypted messages to
      the intended targets in the cell to maintain this signal transduction. CBL
      interacting protein kinases (CIPKs) are crucial components of Ca2+ signal
      transduction during various abiotic stresses. Although there are intron rich
      CIPKs in the plant genome but very little has been reported about their
      alternative splicing. Moreover the physiological significance of this event in
      the Ca2+ signaling is still elusive. Therefore in this study, we have selected
      CIPK3, which has highest number of splice variants amongst Arabidopsis CIPKs.
      Expression profiling of five splice variants of CIPK3 by qRT-PCR in four
      Arabidopsis thaliana ecotypes revealed preferential transcript accumulation but
      similar subcellular localization of the variants and interaction with similar
      CBLs. ABA and drought treatment resulted in the higher accumulation of the
      alternately spliced transcripts of CIPK3 in Arabidopsis ecotype Wassilewkija. The
      transcripts of CIPK3.1 and CIPK3.4 are relatively more induced compared to other
      alternative splice variants. Out of four splice variants studied, we found
      CIPK3.1 and CIPK3.2 showing preference for ABR1, a previously reported interactor
      of CIPK3. We conclude that the differential expression and choice of downstream
      partner by CIPK3-splice variants might be one of the mechanisms of Ca2+ mediated
      preferential regulation of ABA and other stress signals.

PMID- 29225608
TI  - Transcriptomic Profiling and Physiological Responses of Halophyte Kochia
      sieversiana Provide Insights into Salt Tolerance.
AB  - Halophytes are remarkable plants that can tolerate extremely high-salinity
      conditions, and have different salinity tolerance mechanisms from those of
      glycophytic plants. In this work, we investigated the mechanisms of salinity
      tolerance of an extreme halophyte, Kochia sieversiana (Pall.) C. A. M, using RNA
      sequencing and physiological tests. The results showed that moderate salinity
      stimulated the growth and water uptake of K. sieversiana and, even under 480-mM
      salinity condition, K. sieversiana maintained an extremely high water content.
      This high water content may be a specific adaptive strategy of K. sieversiana to
      high salinity. The physiological analysis indicated that increasing succulence
      and great accumulations of sodium, alanine, sucrose, and maltose may be favorable
      to the water uptake and osmotic regulation of K. sieversiana under high-salinity
      stress. Transcriptome data indicated that some aquaporin genes and potassium (K+)
      transporter genes may be important for water uptake and ion balance,
      respectively, while different members of those gene families were employed under
      low- and high-salinity stresses. In addition, several aquaporin genes were up
      regulated in low- but not high-salinity stressed roots. The highly expressed
      aquaporin genes may allow low-salinity stressed K. sieversiana plants to uptake
      more water than control plants. The leaf K+/root K+ ratio was enhanced under low-
      but not high-salinity stress, which suggested that low salinity might promote K+
      transport from the roots to the shoots. Hence, we speculated that low salinity
      might allow K. sieversiana to uptake more water and transport more K+ from roots
      to shoots, increasing the growth rate of K. sieversiana.

PMID- 29225609
TI  - Efficiency of Trichome-Based Plant Defense in Phaseolus vulgaris Depends on
      Insect Behavior, Plant Ontogeny, and Structure.
AB  - Plant trichomes often function as physical barriers in preventing arthropod
      feeding and oviposition. Even though insects are frequently reported being
      entrapped and killed by trichome traps, the actual trapping behavior has not yet
      been described in detail. Capture experiments showed that capture efficiency
      during the plant's vegetative stage was considerably higher than in the fruiting
      and cotyledon stages. The ventral surface of the leaf was more effective in
      trapping flies than other parts of the plant. Capture-events monitoring showed
      that the mouthparts, legs, and ovipositor of Liriomyza trifolii adults are the
      body parts involved in entrapment by surface trichomes on Phaseolus vulgaris
      plants, and subsequently, deter their ability to feed, walk, and oviposit. Of the
      three main body parts normally affected, mouthparts was found to be the body part
      most susceptible to the trichomes. Entrapments were most often caused by landing,
      followed by puncturing or feeding, and occasionally by walking or fighting. Using
      scanning electron microscopy (SEM) and optical microscopy, we determined the
      susceptible positions of each body part and found that the flies were all trapped
      by hooked trichomes. This study revealed the process by which leafminer flies are
      entrapped by surface trichomes of the host plant and evaluated the capture
      efficiency. The results will contribute to our understanding of physical defenses
      against herbivores.

PMID- 29225610
TI  - Horizontal Gene Transfer Contributes to Plant Evolution: The Case of
      Agrobacterium T-DNAs.
AB  - Horizontal gene transfer (HGT) can be defined as the acquisition of genetic
      material from another organism without being its offspring. HGT is common in the
      microbial world including archaea and bacteria, where HGT mechanisms are widely
      understood and recognized as an important force in evolution. In eukaryotes, HGT
      now appears to occur more frequently than originally thought. Many studies are
      currently detecting novel HGT events among distinct lineages using next
      generation sequencing. Most examples to date include gene transfers from
      bacterial donors to recipient organisms including fungi, plants, and animals. In
      plants, one well-studied example of HGT is the transfer of the tumor-inducing
      genes (T-DNAs) from some Agrobacterium species into their host plant genomes.
      Evidence of T-DNAs from Agrobacterium spp. into plant genomes, and their
      subsequent maintenance in the germline, has been reported in Nicotiana, Linaria
      and, more recently, in Ipomoea species. The transferred genes do not produce the
      usual disease phenotype, and appear to have a role in evolution of these plants.
      In this paper, we review previous reported cases of HGT from Agrobacterium,
      including the transfer of T-DNA regions from Agrobacterium spp. to the
      sweetpotato [Ipomoea batatas (L.) Lam.] genome which is, to date, the sole
      documented example of a naturally-occurring incidence of HGT from Agrobacterium
      to a domesticated crop plant. We also discuss the possible evolutionary impact of
      T-DNA acquisition on plants.

PMID- 29225611
TI  - Overexpression of TaWRKY146 Increases Drought Tolerance through Inducing Stomatal
      Closure in Arabidopsis thaliana.
AB  - As a superfamily of transcription factors, the tryptophan-arginine-lysine
      tyrosine (WRKY) transcription factors have been found to be essential for abiotic
      and biotic stress responses in plants. Currently, only 76 WRKY transcription
      factors in wheat could be identified in the NCBI database, among which only a few
      have been functionally analyzed. Herein, a total of 188 WRKY transcription
      factors were identified from the wheat genome database, which included 123 full
      length coding sequences, and all of them were used for detailed evolution
      studies. By bioinformatics analysis, a WRKY transcription factor, named
      TaWRKY146, was found to be the homologous gene of AtWRKY46, overexpression of
      which leads to hypersensitivity to drought and salt stress in Arabidopsis.
      Consequently, the full length of TaWRKY146 was cloned, and the expression levels
      of TaWRKY146 were found significantly up-regulated in the leaves and roots of
      wheat seedlings, which were subjected to osmotic stress. Overexpression of
      TaWRKY146 in Arabidopsis was shown to enhance drought tolerance by the induction
      of stomatal closure that reduced the transpiration rate. All these results
      provide a firm foundation for further identification of WRKY transcription
      factors with important functions in wheat.

PMID- 29225612
TI  - Hidden Diversity in the Populations of the Armored Catfish Ancistrus Kner, 1854
      (Loricariidae, Hypostominae) from the Parana River Basin Revealed by Molecular
      and Cytogenetic Data.
AB  - Only one species of armored catfish, Ancistrus cirrhosus Valenciennes 1836, has
      been historically described in the basin of the Parana River, from Misiones
      (Argentina). However, the ample variation found in the morphology and coloration
      of the populations sampled in the tributaries of the Brazilian state of Parana
      makes it difficult to establish the real taxonomic status and evolutionary
      history of the Ancistrus specimens, suggesting that A. cirrhosus is not the only
      species found in this basin. By combining data on mitochondrial DNA (COI gene)
      and chromosomal markers from different Ancistrus populations, totaling 144
      specimens, in the tributaries of the Parana, and specimens from Misiones (type
      locality of A. cirrhosus), we detected five distinct evolutionary lineages. All
      the specimens were 2n = 50, but had four distinct karyotype formulae. The results
      of the Generalized Mixed Yule Coalescent (GYMC) and the genetic distances
      (uncorrected P-values) between lineages ranged from 3 to 5%. Clusters of 18S rDNA
      were observed in a single chromosome pair in seven populations of Ancistrus, but
      at different positions, in some cases, in synteny with the 5S rDNA sites.
      Multiple 5S sites were observed in all populations. Overall, the cytogenetic data
      reinforce the genetic evidence of the diversification of lineages, and indicate
      the existence of candidate species in the study region. The evidence indicates
      that at least four candidate species of the Ancistrus may coexist in the Parana
      basin besides A. cirrhosus. Overall, our results provide a comprehensive scenario
      for the genetic variation among Ancistrus populations and reinforce the
      conclusion that the true diversity of the freshwater fish of the Neotropical
      regions has been underestimated.

PMID- 29225613
TI  - A Multitasking Electrical Impedance Tomography System Using Titanium Alloy
      Electrode.
AB  - This paper presents a multitasking electrical impedance tomography (EIT) system
      designed to improve the flexibility and durability of an existing EIT system. The
      ability of the present EIT system to detect, locate, and reshape objects was
      evaluated by four different experiments. The results of the study show that the
      system can detect and locate an object with a diameter as small as 1.5 mm in a
      testing tank with a diameter of 134 mm. Moreover, the results demonstrate the
      ability of the current system to reconstruct an image of several dielectric
      object shapes. Based on the results of the experiments, the programmable EIT
      system can adapt the EIT system for different applications without the need to
      implement a new EIT system, which may help to save time and cost. The setup for
      all the experiments consisted of a testing tank with an attached 16-electrode
      array made of titanium alloy grade 2. The titanium alloy electrode was used to
      enhance EIT system's durability and lifespan.

PMID- 29225614
TI  - New Transcriptional Reporters to Quantify and Monitor PPARgamma Activity.
AB  - The peroxisome-proliferator-activated-receptor-gamma (PPARgamma) is a member of
      the nuclear receptor superfamily that plays a critical role in diverse biological
      processes, including adipogenesis, lipid metabolism, and placental development.
      To study the activity of PPARgamma, we constructed two new reporter genes: a
      fluorescent GFP-tagged histone-2B (PPRE-H2B-eGFP) and a secreted nanoluciferase
      (PPRE-pNL1.3[secNluc]). This study demonstrates their usage to monitor PPARgamma
      activity in different cell types and screen for PPARgamma's potential ligands.

PMID- 29225616
TI  - Multimodal Personal Verification Using Likelihood Ratio for the Match Score
      Fusion.
AB  - In this paper, the authors present a novel personal verification system based on
      the likelihood ratio test for fusion of match scores from multiple biometric
      matchers (face, fingerprint, hand shape, and palm print). In the proposed system,
      multimodal features are extracted by Zernike Moment (ZM). After matching, the
      match scores from multiple biometric matchers are fused based on the likelihood
      ratio test. A finite Gaussian mixture model (GMM) is used for estimating the
      genuine and impostor densities of match scores for personal verification. Our
      approach is also compared to some different famous approaches such as the support
      vector machine and the sum rule with min-max. The experimental results have
      confirmed that the proposed system can achieve excellent identification
      performance for its higher level in accuracy than different famous approaches and
      thus can be utilized for more application related to person verification.

PMID- 29225615
TI  - Epileptic Seizure Prediction Using CSP and LDA for Scalp EEG Signals.
AB  - This paper presents a patient-specific epileptic seizure predication method
      relying on the common spatial pattern- (CSP-) based feature extraction of scalp
      electroencephalogram (sEEG) signals. Multichannel EEG signals are traced and
      segmented into overlapping segments for both preictal and interictal intervals.
      The features extracted using CSP are used for training a linear discriminant
      analysis classifier, which is then employed in the testing phase. A leave-one-out
      cross-validation strategy is adopted in the experiments. The experimental results
      for seizure prediction obtained from the records of 24 patients from the CHB-MIT
      database reveal that the proposed predictor can achieve an average sensitivity of
      0.89, an average false prediction rate of 0.39, and an average prediction time of
      68.71 minutes using a 120-minute prediction horizon.

PMID- 29225617
TI  - Fecal Calprotectin: A Reliable Predictor of Mucosal Healing after Treatment for
      Active Ulcerative Colitis.
AB  - Objectives: Mucosal healing has become the new goal of treatment in ulcerative
      colitis. Fecal calprotectin has been demonstrated to differentiate between
      mucosal inflammation and mucosal healing. With this project, we investigated
      whether a reduction in f-calprotectin to <250 MUg/g after medical treatment for
      active ulcerative colitis could predict mucosal healing. Material and Methods:
      After a baseline colonoscopy, 20 patients with active ulcerative colitis were
      followed with consecutive fecal calprotectin monthly until two measurements of
      fecal calprotectin < 250 MUg/g or a maximum follow-up of 12 months. A flexible
      sigmoidoscopy was then performed and Mayo endoscopic subscore was used to
      evaluate degree of inflammation. Simple Clinical Colitis Activity Index was used
      for evaluation of clinical disease activity. Results: A total of 16 patients
      achieved fecal calprotectin < 250 MUg/g during follow-up, and all 16 patients had
      endoscopic mucosal healing (Mayo endoscopic subscore of <=1) on the second
      endoscopy. The remaining four patients had persistently high f-calprotectin
      levels before the second endoscopy with Mayo endoscopic subscore corresponding to
      endoscopic mucosal healing in three out of four patients. Conclusions: Fecal
      calprotectin <250 MUg/g after medical treatment for active ulcerative colitis is
      a reliable marker of endoscopic mucosal healing.

PMID- 29225618
TI  - Influence of Enhanced Recovery Pathway on Surgical Site Infection after Colonic
      Surgery.
AB  - Background: The present study aimed to evaluate a potential effect of ERAS on
      surgical site infections (SSI). Methods: Colonic surgical patients operated
      between May 2011 and September 2015 constituted the cohort for this retrospective
      analysis. Over 100 items related to demographics, surgical details, compliance,
      and outcome were retrieved from a prospectively maintained database. SSI were
      traced by an independent National surveillance program. Risk factors for SSI were
      identified by univariate and multinomial logistic regression. Results: Fifty-four
      out of 397 patients (14%) developed SSI. Independent risk factors for SSI were
      emergency surgery (OR 1.56; 95% CI 1.09-1.78, p = 0.026), previous abdominal
      surgery (OR 1.7; 95% CI 1.32-1.87, p = 0.004), smoking (OR 1.71; 95% CI 1.22
      1.89, p = 0.014), and oral bowel preparation (OR 1.86; 95% CI 1.34-1.97, p =
      0.013), while minimally invasive surgery (OR 0.3; 95% CI 0.16-0.56, p < 0.001)
      protected against SSI. Compliance to ERAS items of >70% was not retained as a
      protective factor for SSI after multivariate analysis (OR 0.94; 95% CI 0.46-1.92,
      p = 0.86). Conclusions: Smoking, open and emergency surgery, and bowel
      preparation were risk factors for SSI. ERAS pathway had no independent impact
      while minimally invasive approach did. This study was registered under
      ResearchRegistry.com (UIN researchregistry2614).

PMID- 29225619
TI  - Clinical Application of CT-Guided Percutaneous Microwave Ablation for the
      Treatment of Lung Metastasis from Colorectal Cancer.
AB  - Objective: The aim of our research is to explore the clinical efficacy and safety
      of CT-guided percutaneous microwave ablation (MWA) for the treatment of lung
      metastasis from colorectal cancer. Materials and Methods: CT-guided percutaneous
      MWA was performed in 22 patients (male 14, female 8, mean age: 56.05 +/- 12.32
      years) with a total of 36 lung metastatic lesions from colorectal cancer between
      February 2014 and May 2017. Clinical data were retrospectively analyzed with
      respect to the efficacy, safety, and outcome. Results: Of the 36 lesions, 34
      lesions (94.4%) reduced obviously with small cavitations or fibrous stripes
      formed and had no evidence of recurrence during follow-up. The volume of the
      other 2 lesions demonstrated local progression after 6 months by follow-up CT.
      The primary complications included pneumothorax (28%), chest pain (21%), and
      fever (5%). These symptoms and signs were obviously relieved or disappeared after
      several-day conservative treatment. The mean follow-up of the patients was 25.54
      +/- 12.58 months (range 2-41 months). The estimated progression-free survival
      rate was 94.4%. Conclusion: Our results demonstrate that CT-guided percutaneous
      MWA appears to be an effective, reliable, and minimally invasive method for the
      treatment of lung metastasis from colorectal cancer. This trial is registered
      with ChiCTR-ORC-17012904.

PMID- 29225620
TI  - The Internet Use for Health Information Seeking among Ghanaian University
      Students: A Cross-Sectional Study.
AB  - The aim of the study was to investigate university students' use of the Internet
      for health purpose in the Ghanaian context. The study employed a quantitative
      cross-sectional design. A total of 650 out of 740 students selected from 3
      different universities participated, giving a response rate of 87.7% (650/740).
      Data were obtained using questionnaires and frequency and percentages were used
      to analyze data. The results show that university students are active users of
      the Internet as 78.3% (509/650) used Internet daily and 67.7% (440/650) use
      Internet for health purposes, for reasons including availability and ease of
      accessing information, privacy, confidentiality, and affordability. Use of
      Internet was constrained by unreliable and slow connection, high cost of
      Internet, and unreliable power supply. Also, 72.4% (315/435) used the online
      health information obtained as a basis for lifestyle change and only 39.5%
      (170/430) consulted health professionals after obtaining online information. The
      study concludes that students use Internet to seek online health support. The use
      of Internet to communicate with young people in relation to their health must
      therefore be explored. There is the need to be aware of online safety issues for
      young adults, including the need to provide information on privacy options.

PMID- 29225621
TI  - Improved Health Status and Life Satisfaction among Older People following Self
      Help Group Intervention in Jakarta.
AB  - Although self-help group for older people gains the effectiveness, the effect of
      a nursing intervention using a self-help group model as a guideline for self
      monitoring and intervention on the health status and life satisfaction among
      older people still remains. To determine the effectiveness of this nursing
      intervention, an experimental design using multistage sampling method was used
      for this study. The self-help intervention included a single 50-70-minute session
      once a week for 12 weeks done, using the Life Satisfaction Inventory-A (LSI-A)
      questionnaire, and SF-36 shows a significant difference. Self-help intervention
      could be implemented by nurses for older people in the community to improve
      health and well-being.

PMID- 29225622
TI  - Correlation between CH2DS2-VASc Score and Serum Leptin Levels in Cardioembolic
      Stroke Patients: The Impact of Metabolic Syndrome.
AB  - Objective: To determine adipokines levels in patients with different etiologic
      subtypes of acute ischemic stroke (AIS) and metabolic syndrome (MetS) status.
      Methods: Serum adiponectin, leptin, and resistin levels were determined by ELISA
      in 99 AIS patients and 59 stroke-free control group subjects. Stroke patients
      were grouped based on MetS, modified TOAST classification, and CHA2DS2-VASc scale
      in case of cardioembolic stroke following atrial fibrillation. Results: No
      differences were found in all adipokine serum levels between AIS patients and
      appropriately matched control group. MetS-AIS patients had significantly higher
      leptin levels (22.71 +/- 19.01 ng/ml versus 8.95 +/- 9.22 ng/ml, p < 0.001) and
      lower adiponectin levels (10.71 +/- 8.59 ng/ml versus 14.93 +/- 10.95 ng/ml, p <
      0.05) than non-MetS-AIS patients. In patients with cardioembolic stroke, leptin
      levels were significantly higher than in remaining stroke cases (19.57 +/- 20.53
      ng/ml versus 13.17 +/- 12.36 ng/ml, p < 0.05) and CHA2DS2-VASc score positively
      correlated with leptin levels only (p < 0.001). Analysis of individual components
      of CHA2DS2-VASc score showed that hypertension, female gender, and diabetes had
      greatest impact on elevated serum leptin level. Conclusion: This pilot study
      revealed that leptin could be a potential biomarker for risk stratification of
      cardioembolic stroke in MetS patients and that heterogeneity of stroke subtypes
      should be considered for more refined and precise clinical stroke studies.

PMID- 29225623
TI  - Ki-67 Expression by Immunohistochemistry and Quantitative Real-Time Polymerase
      Chain Reaction as Predictor of Clinical Response to Neoadjuvant Chemotherapy in
      Locally Advanced Breast Cancer.
AB  - Background: Chemotherapy has become a standard of treatment in managing breast
      cancer. To achieve proper treatment for the right patients, the predictive marker
      is needed. Ki-67 is a biomarker of proliferation for solid tumor. Studies
      mentioned association of Ki-67 expression with chemotherapy response. The study
      aims are to evaluate whether Ki-67 expression detected by immunohistochemistry
      (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) may predict
      clinical response to neoadjuvant chemotherapy in breast cancer. Methods: This
      study utilized a longitudinal study. IHC and qRT-PCR methods were used for
      detection of Ki-67 expression. Chemotherapy response was calculated using RECIST.
      Data were analyzed with Chi-square and Wilcoxon's test. Results: There were 48
      subjects in this study. Analysis of Ki-67 expression with chemotherapy response
      has a significant correlation with p = 0.025 (<0.05), OR: 1.69, confidence
      interval (95% CI) 1.022-2.810. Analysis of Ki-67 mRNA expression with
      chemotherapy response has a significant correlation p = 0.002 (<0.05), OR: 6.85,
      confidence interval (95% CI) 1.064-44.193. Detection of Ki-67 expression using
      IHC and qRT-PCR has similar results, p = 0.012 (<0.05). Conclusion: These results
      suggest that Ki-67 expression detected by both IHC and qRT-PCR is considered to
      be a predictor of clinical response to neoadjuvant chemotherapy in locally
      advanced breast cancer.

PMID- 29225624
TI  - A Competition between Care Teams Improved Recording of Diagnoses in Primary
      Dental Care: A Longitudinal Follow-Up Study.
AB  - Introduction: A playful competition was launched in a primary dental health care
      system to improve the recording of diagnoses into an electronic patient chart
      system and to study what diagnoses were used in primary dental care. Methods:
      This was a longitudinal follow-up study with public sector primary dental care
      practices in a Finnish city. A one-year-lasting playful competition between the
      dental care teams was launched and the monthly percentage of dentists' visits
      with recorded diagnosis before, during, and after the intervention was recorded.
      The assessed diagnoses were recorded with the International Classification of
      Diseases (ICD-10). Results: Before the competition, the level of diagnosis
      recordings was practically zero. At the end of this intervention, about 25% of
      the visits had a recorded diagnosis. Two years after the competition, this
      percentage was 35% without any additional measures. The most frequent diagnoses
      were dental caries (K02, 38.6%), other diseases of hard tissues of teeth (K03,
      14.8%), and diseases of pulp and periapical tissues (K04, 11.4%). Conclusions:
      Commitment to the idea that recording of diagnoses was beneficial improved the
      recording of dental diagnoses. However, the diagnoses obtained did not accurately
      reflect the reputed prevalence of oral diseases in the Finnish population.

PMID- 29225626
TI  - Hemothorax due to Ruptured Mycotic Aneurysm of Intercostal Arteries Associated
      with Infective Endocarditis.
AB  - We present a case of hemothorax due to ruptured mycotic aneurysm in three
      intercostal arteries in a 40-year-old male with methicillin-resistant
      Staphylococcus aureus infective endocarditis (IE) due to intravenous drug use.
      Microcoil embolization and thoracotomy successfully achieved hemostasis. Mycotic
      aneurysm is a rare complication of IE and is usually found in the intracranial
      vessels. Ruptured mycotic aneurysm in the intercostal arteries can be associated
      with IE and can present as acute hemothorax.

PMID- 29225625
TI  - Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis
      Receiving Biologic or Nonbiologic DMARDs.
AB  - Safety concerns associated with many drugs indicated for the treatment of
      rheumatoid arthritis (RA) can be attenuated by the early identification of
      toxicity through routine laboratory monitoring; however, a comprehensive review
      of the recommended monitoring guidelines for the different available RA therapies
      is currently unavailable. The aim of this review is to summarize the current
      guidelines for laboratory monitoring in patients with RA and to provide an
      overview of the laboratory abnormality profiles associated with each drug
      indicated for RA. Recommendations for the frequency of laboratory monitoring of
      serum lipids, liver transaminases, serum creatinine, neutrophil counts, and
      platelet counts in patients with RA were compiled from a literature search for
      published recommendations and guidelines as well as the prescribing information
      for each drug. Laboratory abnormality profiles for each drug were compiled from
      the prescribing information for each drug and a literature search including meta
      analyses and primary clinical trials data.

PMID- 29225627
TI  - Isolation and Molecular Characterization of Amniotic Fluid-Derived Mesenchymal
      Stem Cells Obtained from Caesarean Sections.
AB  - Human amniotic fluid cells are immune-privileged with low immunogenicity and anti
      inflammatory properties. They are able to self-renew, are highly proliferative,
      and have a broad differentiation potential, making them amenable for cell-based
      therapies. Amniotic fluid (AF) is routinely obtained via amniocentesis and
      contains heterogeneous populations of foetal-derived progenitor cells including
      mesenchymal stem cells (MSCs). In this study, we isolated human MSCs from AF (AF
      MSCs) obtained during Caesarean sections (C-sections) and characterized them.
      These AF-MSCs showed typical MSC characteristics such as morphology, in vitro
      differentiation potential, surface marker expression, and secreted factors.
      Besides vimentin and the stem cell marker CD133, subpopulations of AF-MSCs
      expressed pluripotency-associated markers such as SSEA4, c-Kit, TRA-1-60, and TRA
      1-81. The secretome and related gene ontology (GO) terms underline their immune
      modulatory properties. Furthermore, transcriptome analyses revealed similarities
      with native foetal bone marrow-derived MSCs. Significant KEGG pathways as well as
      GO terms are mostly related to immune function, embryonic skeletal system, and
      TGFbeta-signalling. An AF-MSC-enriched gene set included putative AF-MSC markers
      PSG5, EMX-2, and EVR-3. In essence, C-section-derived AF-MSCs can be routinely
      obtained and are amenable for personalized cell therapies and disease modelling.

PMID- 29225628
TI  - Noncoding RNA and Cardiomyocyte Proliferation.
AB  - It is acknowledged that postnatal mammalian cardiomyocytes (CMs) turn over with a
      very limited efficacy in both physiological and pathological conditions. Recent
      studies showed that those newly formed CMs are derived from preexisting CMs.
      Thus, stimulating CM proliferation becomes a promising strategy for inducing
      cardiac regeneration. Noncoding RNAs were found differently expressed in CMs with
      different proliferation potential. Moreover, manipulation of noncoding RNAs, in
      particular microRNAs, was proved to promote or suppress CM proliferation,
      indicating that noncoding RNAs are involved in the underlying mechanism of CM
      proliferation. This review mainly summarizes the roles of noncoding RNAs, as a
      class of influential factors, in the regulation of CM proliferation.

PMID- 29225629
TI  - Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as
      In Vitro Antiplasmodial Hits.
AB  - A total of 28 lapachol-related naphthoquinones with four different scaffolds were
      synthesized and spectroscopically characterized. In vitro antiplasmodial activity
      was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by
      the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16
      cell was determined by the MTT assay. All compounds disclosed higher in vitro
      antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a
      furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1'
      alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more
      cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD
      enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding
      energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan
      ring are highlighted as new in vitro antiplasmodial lead compounds and warrant
      further investigation.

PMID- 29225631
TI  - Initial intravenous immunoglobulin doses should be based on adjusted body weight
      in obese patients with primary immunodeficiency disorders.
AB  - Background: Immunoglobulin therapy plays a critical role in the treatment of
      immunodeficiency disorders as well as autoimmune and inflammatory conditions. In
      immunodeficient patients, there has been controversy whether initial loading
      doses of intravenous (IVIG) should be based on actual body weight or a calculated
      parameter such as adjusted body weight in obese patients. Case presentation: I
      describe a patient with Common Variable Immunodeficiency disorder (CVID) who
      underwent bariatric surgery for morbid obesity. Her weight decreased by 50% to
      below her calculated ideal body weight (IBW) while her immunoglobulin requirement
      fell by approximately 20%. Her steady state serum IgG increased from
      approximately 7 g/l to 11.7 g/l concomitant with weight loss. Conclusions: I
      present this observation as support for the recommendation that initial loading
      doses of SCIG/IVIG in immunodeficiency should be based on adjusted body weight
      (AjBW) and not actual body weight in obese patients. This has important fiscal
      implications for treating obese patients with immunodeficiency disorders.

PMID- 29225630
TI  - Bio- and chemocatalysis cascades as a bridge between biology and chemistry for
      green polymer synthesis.
AB  - The development and integration of bio- and chemocatalytic processes to convert
      renewable or biomass feedstocks into polymers is a vibrant field of research with
      enormous potential for environmental protection and the mitigation of global
      warming. Here, we review the biotechnological and chemical synthetic strategies
      for producing platform monomers from bio-based sources and transforming them into
      eco-polymers. We also discuss their advanced bio-application using the example of
      polylactide (PLA), the most valuable green polymer on the market.

PMID- 29225632
TI  - Recent Advances in Root Canal Disinfection: A Review.
AB  - The microbial biofilm is an important factor for human infection. Finding
      effective antimicrobial strategies should be considered for decreasing
      antimicrobial resistance and controlling the infectious diseases. Treatment of
      infected canal systems may not be able to remove all bacteria and so bacterial
      persistence after treatment may occur. Application of antibacterial nanoparticles
      may be a potential strategy to improve the elimination of bacteria from the
      canal. Furthermore, mechanism of action and applications of photodynamic therapy
      and Photon-induced photoacoustic streaming (PIPS) and GentleWave system was
      reviewed.

PMID- 29225634
TI  - Efficiency of Different Endodontic Irrigation and Activation Systems in Removal
      of the Smear Layer: A Scanning Electron Microscopy Study.
AB  - Introduction: This in vitro study was designed to evaluate and compare different
      endodontic irrigation and activation systems for removal of the intracanal smear
      layer. Methods and Materials: Forty recently extracted, non-carious human intact
      single rooted premolars were selected and divided into five groups (n=10)
      according to the root canal irrigation systems; syringe and needle irrigation
      (CTR), sonic irrigation, passive ultrasonic irrigation (PUI) and EndoVac
      irrigation system. All groups were prepared to #40 apical size with K-files. Each
      sample was subjected to final irrigation by using four different
      irrigation/activation systems. After splitting the samples, one half of each root
      was selected for examination under scanning electron microscope (SEM). The
      irrigation systems were compared using the Fisher's exact test with the level of
      significance set at 0.05. Results: The four groups did not differ from each other
      in the coronal and mid-root parts of the canal. In the apical part of the canal
      none of the methods could completely remove all the smear layer but EndoVac
      system showed significantly better removal of smear layer and debris than the
      other methods. Conclusion: Within the limitations of the present study, the
      EndoVac system cleaned the apical part of the canal more efficiently than sonic,
      ultrasonic and syringe and needle irrigation.

PMID- 29225633
TI  - Genotoxicity, Bioactivity and Clinical Properties of Calcium Silicate Based
      Sealers: A Literature Review.
AB  - An ideal endodontic sealer should have many properties such as excellent seal
      after setting, dimensional stability, slow setting time to ensure sufficient
      working time, insolubility to tissue fluids, adequate adhesion with canal walls
      and biocompatibility. Genotoxicity is one of the important factors that influence
      biocompatibility of an endodontic sealer. This literature review was conducted to
      survey the genotoxicity, bioactivity and clinical perspectives of calcium
      silicate based sealers. We searched PubMed using appropriate MeSH keywords. Also
      a hand search was conducted in the related journals. Sixty eight articles were
      assessed finally. Genotoxicity and acute inflammation were high in calcium
      silicate based sealers. Both resin-based and calcium silicate based sealers
      caused perceptible tooth discoloration. There were controversies regarding the
      fracture resistance, apical patency and retreatability of different sealers.
      Clinical properties of calcium silicate-based sealers are also outlined.

PMID- 29225635
TI  - In Vitro Comparison of Cytotoxicity and Genotoxicity of Three Vital Pulp Capping
      Materials.
AB  - Introduction: Direct pulp capping (DPC) is a treatment for maintaining pulp
      vitality and its biological function. Ideally, pulp capping agents are expected
      to induce pulp cells to form hard tissue. This in vitro study assessed the
      cytotoxicity and genotoxicity of three vital pulp capping (VPC) agents naming
      Biodentine (Septodont, Saint-Maur-des-Fosses, France), mineral trioxide aggregate
      (ProRoot MTA; Dentsply, Tulsa Dental, Tulsa, OK, USA) and TheraCal LC (Bisco Inc,
      Schamburg, IL, USA) on human dental pulp fibroblasts. Methods and Materials:
      Human fibroblasts were exposed to 100 uL of ProRoot MTA, TheraCal LC and
      Biodentine in 0-1000 ug/mL concentrations and incubated at 37 degrees C for 24 h.
      Their cytotoxicity and genotoxicity were assessed using the methyl thiazol
      tetrazolium (MTT) and the comet assays, respectively. The data were analyzed by
      Kruskal-Wallis test at the level of significance set at 0.05. Results: None of
      the tested materials had cytotoxicity or genotoxicity. Conclusion: TheraCal LC,
      Biodentine and ProRoot MTA can be alternately used for VPC treatment of teeth.

PMID- 29225636
TI  - Evaluation of the Prevalence of Complete Isthmii in Permanent Teeth Using Cone
      Beam Computed Tomography.
AB  - Introduction: The current study aimed at determining the prevalence of complete
      isthmii in permanent teeth, using cone-beam computed tomography (CBCT) in a
      selected Iranian community. Methods and Materials: In this cross sectional study,
      100 CBCT images (from 58 female and 42 male patients) including 1654 teeth (809
      maxillary and 845 mandibular teeth) were evaluated. Each tooth root was evaluated
      in axial plane (interval, 0.1 mm; thickness, 0.1 mm) from the orifice to the apex
      and from the apex to the orifice to detect the presence of complete isthmus.
      Scans of teeth with complete isthmii were reevaluated in axial, sagittal, and
      coronal planes with the thickness, 0.1 mm. Presence and absence of complete
      isthmii in each tooth was reported. The root canal was divided into 3 equal parts
      (cervical, middle and apical thirds), and isthmii were classified with respect to
      the start and end points. Findings were classified into 6 categories with respect
      to the start and end points of the isthmii: 1) the beginning and end in the
      cervical third; 2) the beginning in the cervical third and end in the middle
      third ; 3) the beginning in the cervical third and end in the apical third ; 4)
      the beginning and end in the middle third ; 5) the beginning in the middle third
      and end in the apical third and 5) the beginning and end in the apical third.
      Results: The prevalence of complete isthmus in permanent teeth was 8.6%, and the
      highest prevalence was reported in mesial roots of the mandibular first molars.
      In maxilla, the highest prevalence of complete isthmus was found in mesiobuccal
      roots of the maxillary first molars, whereas in canines and central incisors, no
      isthmii were detected. In the mandible, the lowest prevalence of isthmus was
      found in second premolars. In maxillary molars, isthmii starting and ending in
      the middle third of the root had the highest prevalence. On the other hand,
      isthmii in mandibular molars, from apical or middle third of the root beginning
      to the end of the apical third, had the highest prevalence. Conclusion: As the
      prevalence of complete isthmii was the highest in molars, endodontists should pay
      particular attention to accomplish a successful surgical or nonsurgical root
      canal therapy.

PMID- 29225637
TI  - Incidence of Dentinal Crack after Root Canal Preparation by ProTaper Universal,
      Neolix and SafeSider Systems.
AB  - Introduction: This study aimed to compare the incidence of dentinal crack
      formation by instrumentation with ProTaper Universal system (rotary, multi-file
      system), SafeSider (reciprocation movement, multi-file system) and Neolix
      (rotary, single-file system). Methods and Materials: In this in vitro study, 60
      freshly extracted mandibular first molars were randomly divided into three
      experimental groups (n=15) and a control group containing unprepared teeth
      (n=15). Instrumentation in different groups was accomplished using either
      ProTaper, Neolix or SafeSider systems up to 25/0.08. The teeth were then
      sectioned at 3, 6 and 9 mm from the apex, and observed under a stereomicroscope
      for presence of dentinal cracks. Data were analyzed with Chi square test,
      Fisher's exact test and Bonferroni correction. Results: Micro cracks were seen in
      all experimental groups (13.3% in ProTaper, 26.7% in SafeSider and 40% in
      Neolix). There was a significant difference between Neolix and the control groups
      in microcrack formation (P=0.042). Micro cracks mainly occurred in the coronal
      section (9 mm). No microcrack occurred in the control group. Conclusion: Neolix
      rotary single-file system caused more dentinal cracks compared to the unprepared
      roots. All the instrumentation systems increased the number of micro cracks
      compared to unprepared teeth.

PMID- 29225638
TI  - The Probable Effect of Irrigation Solution and Time on Bond Strength to Coronal
      Dentin: An In Vitro Evaluation.
AB  - Introduction: The aim of this study was to evaluate the effect of root canal
      irrigants on the microtensile bond strength of 2-step self-etch adhesive to
      dentin. Methods and Materials: n this study 36 sound extracted human third molars
      were used. After grinding 3 mm of occlusal surface, teeth were randomly divided
      into 6 groups based on irrigation material naming normal saline, 5.25% sodium
      hypochlorite (NaOCl) and 2% chlorhexidine (CHX) and also irrigation time (5 or 30
      min). Next, teeth were restored with Clearfil SE bond adhesive resin system and
      Z250 composite. The teeth were then thermo cycled by thermo cycling machine, for
      500 cycles between 5o and 55oC with 60 sec dwell time and 12 sec transfer time.
      All samples were sectioned into bucco-lingual slabs. The sections were submitted
      to the micro tensile testing machine at a crosshead speed of 0.5 mm/min until
      fracture. Data was analyzed using the one-way ANOVA test with the level of
      significance set at 0.05. Results: Irrigation with normal saline, 5.25% NaOCl and
      2% CHX for 5 or 30 min did not significantly change the microtensile bond
      strength of adhesive to dentin (P=0.729 for time and P=0.153 for material).
      However the maximum and minimum microtensile bond strength was attributed to
      normal saline (44.13 N) and NaOCl (31.29 N) groups, respectively. Conclusion:
      Iirrigation solution and time have no influence on microtensile bond strength of
      two-step self-etch adhesive to coronal dentin.

PMID- 29225639
TI  - The Effect of BC Sealer, AH-Plus and Dorifill on Push-out Bond Strength of Fiber
      Post.
AB  - Introduction: Dentinal canal walls are in direct contact with endodontic sealers
      prior to post space preparation and luting cements after post space preparation.
      This direct contact may affect the bond strength of intraradicular posts to root
      dentin. This study aimed to assess the effect of three different sealers on the
      bond strength of fiber posts to root dentin. Methods and Materials: The canals of
      56 extracted single-rooted human premolars after selection and decoronation were
      prepared. For obturation of the canals, specimens were randomly divided into four
      groups (n=14) according to the type of sealer used in conjunction with gutta
      percha: group 1 (control) without any sealer; group 2 with AH-Plus sealer (resin
      based); group 3 with Dorifill sealer (ZOE-based); and group 4 with BC Sealer
      (calcium silicate-based). Nine mm-deep post space was prepared in the canal of
      each specimen. Intraradicular fiber posts were cemented using dual-cure resin
      cement (Panavia F2.0). Sections of 1 mm thickness were made at the coronal,
      middle and apical thirds of the post space of each specimen. The push-out bond
      strength of post to root dentin was measured in a universal testing machine. The
      data were analyzed using one-way ANOVA and post-hoc Tukey's test. Results: The
      mean push-out bond strength in the coronal third was significantly lower in
      Dorifill group compared to AH-Plus (P=0.004). This value was significantly lower
      in BC Sealer group than AH-Plus (P=0.000) and control group (P=0.03). In middle
      and apical thirds, the mean push-out bond strength was not significantly
      different among the four groups (P=0.407, P=0.065, respectively). The mean push
      out bond strength was significantly lower in apical than coronal third in AH-Plus
      group (P=0.001). Conclusion: Application of BC Sealer and Dorifill decreased the
      mean push-out bond strength of intracanal post to root dentin in the coronal
      third in comparison to AH-Plus.

PMID- 29225640
TI  - Anesthetic Efficacy of Articaine and Ketamine for Inferior Alveolar Nerve Block
      in Symptomatic Irreversible Pulpitis: A Prospective Randomized Double-Blind
      Study.
AB  - Introduction: The aim of this prospective, randomized, double-blind study was to
      investigate the effect of articaine combined with ketamine on the success rate of
      inferior alveolar nerve block (IANB) in posterior mandible teeth with symptomatic
      irreversible pulpitis. Methods and Materials: Forty two adult patients with
      diagnosis of symptomatic irreversible pulpitis of a mandibular posterior tooth
      were selected. The patients received two cartridges of either containing 3.2 mL
      4% articaine with epinephrine 1:200000 and 0.4 mL 50 mg/mL ketamine hydrochloride
      (A-ketamine group) or 3.2 mL 4% articaine with epinephrine 1:200000 and 0.4 mL
      normal saline (A-saline group) using conventional IANB injections. Access cavity
      preparation started 15 min after injection. Lip numbness was required for all the
      patients. Success was considered as no or mild pain on the basis of Heft-Parker
      visual analog scale recordings upon access cavity preparation or initial
      instrumentation. Data were analyzed by independent student t, Mann-Whitney and
      Chi-square tests. Results: The success rates were 55% and 42.9% for A-ketamine
      and A-saline group, respectively, with no significant differences between the two
      groups (P=0.437). Conclusion: Adding 0.4 mL 50 mg/mL ketamine hydrochloride to
      the articaine local anesthetic did not increase the efficacy of IANB for
      posterior mandibular teeth with symptomatic irreversible pulpitis.

PMID- 29225641
TI  - Foramen Changes following Over Instrumentation of Curved Canals with Three Engine
      Driven Instruments: An In Vitro Study.
AB  - Introduction: The present in vitro study aimed to evaluate and compare the
      changes in shape and surface area of the major foramen following shaping of
      curved canals with three new generation NiTi engine-driven instruments naming
      ProTaper Next, BT RaCe and WaveOne Gold- with 3 different levels of protrusion
      beyond the major apical foramen. Methods and Materials: A total of 45 extracted
      human molars with at least one curved canal were distributed in 3 comparable
      groups of 15 that were instrumented using either ProTaper Next (PTN), BT RaCe
      (BTR) or WaveOne Gold (WOG). The canals were instrumented to the major foramen
      and then over instrumented with the final file 0.5 mm, 1 mm and 1.5 mm beyond the
      foramen. Standardized pre- and post-instrumentation photographs of the foramen
      were obtained for all groups using a stereomicroscope. Foramen shape and surface
      area were evaluated using the AmScope software for measurements and compared
      between groups and levels of instrumentation applying binary conditional logistic
      regression and repeated measures ANOVA. The level of significance was set at
      0.05. Results: Foramen shape tended to gradually change from circular to oval as
      the level of instrumentation increased in all groups. The original foramen shape
      in WOG group remained better than other groups. Foramen surface areas increased
      in all groups with Group BTR demonstrating significantly greater values than the
      other 2 groups. Conclusion: Over instrumentation resulted in apical enlargement
      and ovalization in all 3 groups but with different patterns. These differences
      can be attributed to the final file size, design characteristics and kinematics
      of the 3 systems.

PMID- 29225642
TI  - Comparison of Apical Transportation with the Use of Rotary System and
      Reciprocating Handpiece with Precurved Hand Files: An In Vitro Study.
AB  - Introduction: Success of root canal treatment depends on several factors; among
      which, maintaining the original canal path during mechanical preparation is
      extremely important. This in vitro study aimed to compare apical transportation
      using RaCe NiTi rotary system and precurved stainless steel (SS) hand files in a
      reciprocating handpiece. Methods and Materials: Mesiobuccal canals of 40
      extracted human mandibular first and second molars with 20 to 45 degrees 
      curvatures and 3 to 7 mm curve radius were chosen for this study. After working
      length determination, the teeth were divided into two groups (n=20). Root canals
      were prepared with RaCe in group 1 and NSK handpiece and precurved SS hand files
      in group 2 up to #30 with 2% taper in both groups. Radiographs were taken of
      teeth before and after instrumentation from buccolingual and mesiodistal
      directions. The images were superimposed using Adobe Photoshop CS3 software.
      Degree of straightening and amount of apical transportation at 0, 0.5, 1, 2, 3, 4
      and 5 mm levels short of the working length were determined using digital
      subtraction radiography. The student's t test was used to compare the degree of
      straightening and Mann Whitney test was applied to compare apical transportation
      (millimeters) between the two groups. Results: No significant difference was
      noted between the two groups on buccolingual or mesiodistal views in degree of
      straightening and apical transportation on buccolingual view (P>0.05). However,
      on mesiodistal view, NSK reciprocating handpiece caused greater apical
      transportation at 0. 0.5 and 1 mm levels (P<0.05). Conclusion: The RaCe system
      and precurved SS files in reciprocating handpiece were highly similar in terms of
      degree of straightening and apical transportation. Thus, engine-driven NSK
      reciprocating handpiece can be used as an efficient adjunct for root canal
      preparation.

PMID- 29225643
TI  - Cyclic Fatigue Resistance of WaveOne Gold, ProDesign R and ProDesign Logic Files
      in Curved Canals In Vitro.
AB  - Introduction: Endodontic instruments are developed to provide a better cleaning
      of the root canal system and reduce its risk of fracture. The aim of this study
      was to evaluate the instrumentation time and cyclic fatigue resistance of WaveOne
      Gold, ProDesign R and ProDesign Logic files. Methods and Materials: Thirty Nickel
      titanium (NiTi) rotary instruments were divided into 3 groups (n=10). ProDesign
      Logic file 25/0.06 was used in continuous rotation after glide path preparation.
      WaveOne Gold 25/0.07 and ProDesign R 25/0.06 files were used in reciprocating
      motion. Every file instrumented 3 standardized artificial canals. The average
      time, the number of cycles (NCI) and cyclic fatigue resistance of each file were
      determined through the number of cycles to failure (NCF) in a stainless-steel
      device. The total amount of cycles to fracture was also calculated (NCI+NCF).
      Data was analyzed using the Kruskal-Wallis and Mann-Whitney tests. Results: The
      instrumentation time of the ProDesign Logic file was significantly lower when
      compared to the other files (P=0.019). The longest times to failure were
      presented by ProDesign Logic (182.07 sec) and ProDesign R (152.38 sec) files. The
      same differences were observed for the NCF (910.37 and 761.93). The WaveOne Gold
      group presented a lower NCF as well as a smaller sum of NCI+NCF (748.33) that was
      statistically significant when compared to the other groups (P<0.05)
      respectively. Conclusion: The use of continuous rotational motion in canals with
      a glide path in the ProDesign Logic group led to shorter instrumentation time.
      The cyclic fatigue resistance of ProDesign R and Logic instruments was superior
      to WaveOne Gold. The thermal treatment of the instrument's alloy, its cross
      section and the glide path seems to influence the cyclic fatigue resistance.

PMID- 29225644
TI  - Physical and Chemical Properties of CEM Cement Mixed with Propylene Glycol.
AB  - Introduction: the aim of the present study was to evaluate the influence of
      propylene glycol (PG) on the flowability, microhardness, pH and calcium ion
      release of calcium-enriched mixture (CEM). Methods and Materials: CEM cement was
      mixed with different proportions of PG, as follows: group 1,100% CEM liquid (CL);
      group 2, 100% PG; group 3, 50% PG and group 4, 20% PG. For assessment of
      flowability, methodology of ADA Specification No. 57 was applied. For measuring
      microhardness, 80 cylindrical molds (6*4 mm) were filled with CEM cement and
      divided into 2 subgroups (4, 21 days) and tested using Vickers Test. Data were
      analyzed using the one-way ANOVA test and Tukey's post hoc and student's t test.
      In order to check pH and calcium release, the mixed cements were placed in
      cylindrical molds (5*2 mm). After 3, 24, 72 and 168 h, pH determined by a pH
      meter and the calcium release was measured by an atomic absorption
      spectrophotometer. Data were analyzed using the repeated measure ANOVA, one way
      ANOVA test and Tuckey's post hoc test. Results: The present study showed that the
      presence of PG did not affect the flowability. With the elapse of time,
      microhardness was significantly increased in all groups except CL group.
      Regardless of time, samples with 50% PG showed the lowest pH value which was
      significantly different from other groups (P<0.05) and samples with 100% and 20%
      PG showed significantly higher calcium ion release compared to other group.
      Conclusion: addition of PG did not have any positive or negative effect on the
      flowability and pH of CEM cement but increased its microhardness in long term.
      Calcium ion release also increased in the concentration of 20% and 100%.

PMID- 29225645
TI  - The Effects of Different Ionic Liquid Coatings and the Length of Alkyl Chain on
      Antimicrobial and Cytotoxic Properties of Silver Nanoparticles.
AB  - Introduction: The antibacterial efficacy and toxicity of silver nanoparticles
      (AgNPs) depends on their physicochemical properties including size, shape,
      surface charge and surface coatings. The Objectives of this study were: i) To
      synthesize and characterize positively charged AgNPs coated by different ionic
      liquids with different alkyl chain lengths, ii) To evaluate the antimicrobial
      activity of these nanoparticles against Enterococcus faecalis compared to sodium
      hypochlorite (NaOCl) and chlorhexidine (CHX), iii) To compare the
      cytocompatibility of these solutions against L929 mouse fibroblasts. Methods and
      Materials: AgNPs with positive surface charges capped by two different ionic
      liquids [imidazolium (Im) and pyridinium (Py)] with two alkyl chain lengths (C12
      and C18) were synthesized. Im and Py were also tested as control groups. The
      characterization revealed synthesis of spherical NPs in the size range of 6.7
      18.5 nm with a surface charge ranging from +25 to +58 mV. To standardize the
      comparisons, the surface charge to radius ratio of each nanoparticle was
      calculated. The minimum inhibitory concentrations (MIC) of the AgNP solutions,
      NaOCl and CHX were determined against E. faecalis by a microdilution test. An MTT
      based cytotoxicity assay evaluated the cytotoxicity of the solutions in different
      concentrations on L929 fibroblasts. One-way and two-way ANOVA were used for
      statistical analysis. Results: All tested AgNPs reached MIC90 in significantly
      lower concentrations compared to CHX and NaOCl. C12 Py-coated AgNPs had the
      lowest MIC90 value. CHX and NaOCl were more toxic on fibroblasts than all tested
      AgNPs. Im-coated AgNPs had better compatibility with fibroblasts than Py-coated
      particles; and C12 Im AgNPs had the best biocompatibility. Variations in alkyl
      chain length had no effects on the biocompatibility of AgNPs. Conclusion: Py
      improved the antibacterial efficacy of AgNPs compared to Im; however, it had a
      negative effect on cytocompatibility. Alkyl chain length had no effects on AgNPs'
      bioactivity.

PMID- 29225646
TI  - In Vitro Cytotoxicity and Setting Time Assessment of Calcium-Enriched Mixture
      Cement, Retro Mineral Trioxide Aggregate and Mineral Trioxide Aggregate.
AB  - Introduction: The present study sought to evaluate and compare biocompatibility
      and setting time of Retro mineral trioxide aggregate (MTA), calcium-enriched
      mixture (CEM) and Angelus MTA. Methods and Materials: CEM cement, Angelus MTA and
      Retro MTA were assessed in set and fresh states. Extracts transformed to each
      cavity of three 24-well plates in which 1*104 cell were seeded into each well 24
      h earlier. All specimens were incubated in a humidified incubator with 5% CO2 at
      37 degrees C. Mosmann's tetrazolium toxicity (MTT) assay was used to determine in
      vitro cytotoxicity on L929 mouse fibroblast cell line. Cell viability was
      determined at 1, 24, and 72 h after exposure. The initial setting time was
      measured by 113.4 g Gilmore needle testing. Then, final setting times were
      assessed by the 456.5 g Gilmore needle. Data comparisons were performed using the
      analysis of variance (ANOVA) and Tukey's post hoc test (alpha=0.05). Results: All
      groups in both forms indicated higher cell vitality compared to positive control
      group (P<0.001). After 24 h, the set Retro MTA showed better biocompatibility
      compared to set CEM and set Angelus MTA (P<0.001). Retro MTA showed significantly
      lower initial and final setting time compared to CEM and Angelus MTA (P<0.001).
      Conclusion: Our results indicated the good cell viability values of Retro MTA and
      relatively short period of setting time. It seems a promising alternative
      material in clinical situations where accelerated setting is required. However,
      more clinical and in vivo investigations are needed for a clear decision making.

PMID- 29225647
TI  - Compressive Strength of Mineral Trioxide Aggregate and Calcium-enriched Mixture
      Cement Mixed with Propylene Glycol.
AB  - Introduction: The aim of the present study was to evaluate and compare the
      compressive strength (CS) of mineral trioxide aggregate (MTA) and calcium
      enriched mixture (CEM) cement when mixed with propylene glycol (PG). Methods and
      Materials: Twenty four custom-made split molds with 5 holes in each were
      prepared. Molds were allocated into eight groups (n=15 holes) as follows: Groups
      1,5: CEM and MTA mixed with PG (100%), Groups 2,6: CEM and MTA mixed with PG (20%
      )+CEM or MTA liquid (80%) respectively, Groups 3,7: CEM and MTA mixed with PG
      (50% )+CEM or MTA liquid (50% ) respectively, Groups 4,8: CEM and MTA mixed with
      CEM or MTA liquid respectively as control groups. All specimens were kept in 37
      degrees C in an incubator and the compressive strength was evaluated after 7
      days. Data were analyzed using the Kruskal Wallis and Dunne tests. The level of
      significance was set at 0.05. Results: In all concentration of PG, MTA samples
      showed better results than CEM cement. In CEM samples, adding 20% PG could
      significantly increase the compressive strength in comparison with control group
      and 100% PG (P=0.047 and P=0.011, respectively). In MTA samples, adding 100% and
      50% PG significantly increased the compressive strength of the cement in
      comparison with control group (P=0.037 and, P=0.005, respectively). Conclusion:
      Considering the limitations of the present study, appropriate concentration of PG
      could improve the CS of MTA and CEM cement.

PMID- 29225648
TI  - Evaluating the Accuracy of Two Microleakage Assessment Methods for Mineral
      Trioxide Aggregate and Calcium-enriched Mixture Cement.
AB  - Introduction: Multiple methods for evaluating microleakage have been introduced
      over the years, but there has been no agreement as to which technique will give
      more accurate results. The aim of this study was to compare the accuracy and
      results of fluid filtration and marginal adaptation methods for mineral trioxide
      aggregate (MTA) and calcium-enriched mixture (CEM) cement apical plugs. Methods
      and Materials: A total of 250 single-rooted human teeth were collected. The teeth
      were decoronated, the root canals were prepared and open apex condition was
      stimulated by passing #1 to 4 Peeso Reamer drills from apical foramen. Five teeth
      were selected as the positive and negative controls and the rest of the samples
      were randomly allocated to two groups of MTA and CEM cement plugs. In each group,
      apical plug was placed into the canal. After the apical plugs were completely
      set, microleakage and marginal adaptation of the samples were evaluated using
      fluid filtration method and scanning electron microscopy (SEM), respectively. The
      obtained results were analyzed by independent-samples t test. Results: Gap
      between plug and dentin walls and air bubbles displacement was higher in MTA
      group compared to the CEM cement group, though this difference between MTA group
      and CEM cement group was not statistically significant. Conclusion: According to
      the obtained results, it seems that there is a direct relationship between the
      two methods of microleakage assessment.

PMID- 29225649
TI  - Incidence of Dentinal Defects and Vertical Root Fractures after Endodontic
      Retreatment and Mechanical Cycling.
AB  - Introduction: The aim of this study was to evaluate the incidence of dentinal
      defects and vertical root fractures (VRFs) after endodontic retreatment and
      mechanical cycling (MC). Methods and Materials: Two hundred mandibular premolars
      were selected. Forty teeth were left unprepared (control group). The remaining
      160 root canals were prepared with ProTaper instruments and filled by using two
      different techniques [eighty with lateral compaction (LC) and eighty with single
      cone (SC)]. Forty canals from each group (LC and SC) received no further
      treatment. The remaining eighty teeth were divided into two groups (LCR and SCR)
      (n=40) in order to undergo the removal of the root filling, re-preparation and
      refilling with lateral compaction and single-cone, respectively. All of the teeth
      were subjected to MC (1000000 cycles, 130 N, 2.2 Hz and 37 degrees C). The roots
      were sectioned at 3, 6 and 9 mm from the apex and observed under 20*
      magnification. The defects were classified as: no defect, VRF and other defects.
      Statistical analysis was performed using the Fisher's Exact test and the Chi
      Squared tests (alpha=0.05). Results: MC alone did not promote any other defects
      or VRFs. Experimental groups presented higher dentinal defects than the control
      group (P=0.021). Retreatment groups did not present a higher amount of dentinal
      defects than the groups that were subjected to the first treatment (P>0.05).
      Conclusion: Endodontic treatment and retreatment, regardless of the filling
      technique and MC, did not influence the occurrence of dentinal defects or VRFs in
      the human premolars.

PMID- 29225650
TI  - Maintenance of Pulp after Horizontal Root Fractures in Three Maxillary Incisors:
      A Thirteen-Year Evaluation.
AB  - This case report documents the clinical approach adopted for three upper incisors
      with horizontal root fracture in the middle or cervical third. The proposed
      procedures involved maintaining pulp vitality and periodontal stability of the
      fractured teeth with 13 years of follow-up.

PMID- 29225651
TI  - Multidisciplinary Treatment of a Double First Mandibular Premolar.
AB  - Gemination aka twinning and fusion, are rare occurrences in posterior mandibular
      teeth, often requiring endodontic and surgical treatment for functional,
      orthodontic or cosmetic reasons. The diagnosis and design of a precise treatment
      plan in cases involving double teeth are in most cases challenging. The purpose
      of this case report is to describe a successful multidisciplinary treatment
      protocol for a double tooth. Upon completion of the endodontic, restorative and
      orthodontic treatments, the clinical and radiographic three-year follow-up
      revealed that the rest of the transected premolar showed evidence of healing of
      the supporting tissues and satisfactory cosmetic result.

PMID- 29225652
TI  - Repair of Iatrogenic Furcal Perforation with Mineral Trioxide Aggregate: A Seven
      Year Follow-up.
AB  - Teeth with furcal perforation present difficult resolution and dubious prognosis.
      Several materials have been proposed and calcium silicate-based cements such as
      mineral trioxide aggregate (MTA) are the most recommended. However, its long-term
      clinical behavior still remains poorly understood. The present study reports a
      clinical case of furcal perforation repair using Angelus MTA, with a 7-year
      follow-up. Patient sought treatment 2 months after iatrogenic accident. First
      lower right molar presented clinical signs such as fistula and bone loss between
      mesial and distal roots. Firstly, all root canals were treated and then furcal
      perforation was sealed with MTA Angelus and the dental crown was restored with
      composite resin. Radiographic evaluation was immediately performed to analyze the
      furcal perforation filling. After 7 years, a new clinical and imaging evaluation
      using periapical radiography and cone-beam computed tomography (CBCT) showed
      absence of clinical signs and symptoms, and alveolar bone reconstitution with
      periodontal space reduction. Angelus MTA presented good clinical behavior in the
      iatrogenic furcal perforation resolution based on long-term clinical evidence.

PMID- 29225653
TI  - Nonsurgical Management of an Immature Maxillary Central Incisor with Type III
      Dens Invaginatus Using MTA Plug: A Case Report.
AB  - Dens invaginatus is a developmental anomaly, caused by deepening of the enamel
      organ into the dental papilla before calcification of the dental tissues. Teeth
      with dens invagination are susceptible to early caries and pulp necrosis within a
      few years of eruption or even before root end closure. This article reports two
      immature maxillary central incisors with type I and III dens invaginatus which
      had necrotic pulp and a large periradicular lesion, that were treated
      successfully by nonsurgical root canal treatment. After apical plug placement,
      the remaining space was backfilled using warm vertical gutta-percha technique and
      the crowns were restored by composite restoration. At 6 months of follow up the
      patient was asymptomatic and probing depths were less than 3 mm. In addition, the
      reduction in the size of apical radiolucencies was observed by radiographic
      examinations. This case report revealed that even type III des invaginatus with
      an open apex and large periapical lesion, can be treated non-surgically using MTA
      as an apical plug. Although this case report presents a favorable result, further
      studies with long term follow-up periods are encouraged to support the use of
      nonsurgical endodontic treatment for type III dens invaginatus.

PMID- 29225654
TI  - Clinical Approach to Pulp Canal Obliteration: A Case Series.
AB  - This article describes four cases with safe and feasible clinical treatment
      strategies for anterior teeth with pulp canal obliteration (PCO) using cone-beam
      computed tomography (CBCT), digital radiography (DR), dental operating microscopy
      (DOM) and ultrasonic tips (US). Four anterior teeth with PCO were chosen. DR was
      taken with different angulations and analyzed with different filters.
      Subsequently, the access cavity was performed with the aid of DOM. If the canal
      was not identified, CBCT was requested. Sagittal and axial slices guided the
      direction of the ultrasonic tips. After identification of the canal, it was then
      negotiated and instrumented with the rotary instruments. All four canals were
      successfully identified, with no complications. In case 1, the canal was
      identified using DR, DOM and US tips. In cases 2, 3 and 4, the canals were
      identified with DR, DOM, US tips and CBCT. Complete root canal obliteration
      identified in radiography did not necessarily mean that pulp tissue was not
      visible clinically, either. The clinical evaluation of the access cavity with the
      aid of MO was crucial. If the canal was not identified, CBCT was mandatory in
      order to show more detailed view of the precise position of the canals, their
      directions, degrees of obstruction and dimensions. It served as a guide for the
      direction of the ultrasonic tips to keep them within the pulp chamber safely,
      with a low risk of iatrogenic injury.

PMID- 29225655
TI  - Non-Surgical Endodontic Management of Type II Dens Invaginatus with Closed and
      Open Apex.
AB  - Dens invaginatus (DI) is a developmental anomaly that poses a significant
      challenge to the clinician if endodontic treatment is required. The type II (as
      per Oehlers) form exhibits complex internal anatomy and is frequently associated
      with incomplete root and apex formation. The purpose of this study is to present
      two cases of type II DI in the maxillary lateral incisors. In the first case, non
      surgical endodontic therapy was performed utilizing calcium hydroxide as an
      intracanal dressing, showing significant periapical healing of the apical
      radiolucent area at the six month follow-up. In the second case, the development
      of the root and apex were affected by pulp necrosis, and the revascularization
      procedure was performed. Complete resolution of the pre-existing apical
      radiolucency, apical closure, thickening of the root canal walls, and increase in
      root length, after 32 months was observed. Early detection of teeth with DI type
      II and proper exploration of their internal anatomy are key factors for their
      successful management. As demonstrated in this report, conservative non-surgical
      endodontic treatment should be the first line of treatment for these cases. The
      use of revascularization protocols in teeth that develop pulp necrosis and
      exhibit early stage of root development could be a better alternative than
      traditional apexification techniques.

PMID- 29225656
TI  - Letter to the Editor.

PMID- 29225657
TI  - Satisfaction and quality of life of allergic patients following sublingual five
      grass pollen tablet immunotherapy in Spain.
AB  - Background: Five-grass pollen tablet is an effective and well-tolerated therapy
      for patients with allergic rhinoconjunctivitis (ARC). This trial sought to
      determine the satisfaction and health-related quality of life (HRQoL) of patients
      undergoing this treatment. Methods: This was a cross-sectional, multicentre,
      observational, naturalistic study, following a discontinuous pre- and co-seasonal
      five-grass pollen regimen over two seasons in Spain (2012, 2013). The HRQoL of
      the patients was measured with the specific Rhinoconjunctivitis Quality of Life
      Questionnaire (RQLQ) for adults, adolescent (AdolRQLQ), or paediatric (PRQLQ)
      patients. Treatment satisfaction was assessed by the Satisfaction Scale for
      Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire.
      Patients/investigators were surveyed on beliefs and attitudes towards the five
      grass pollen tablet. ARC evolution according to allergic rhinitis and its impact
      on asthma (ARIA) criteria and treatment adherence were evaluated. Results: Among
      the 591 ARC patients included, the mean (SD) HRQoL scores were 1.40 (1.1) in
      adults, 1.33 (1.1) in adolescents, and 1.15 (1.1) in children, indicating low
      levels of impairment (scale 0-6). ESPIA answers showed high levels of
      satisfaction, with an average score of 69.2 (scale 0-100). According to ARIA
      criteria, 88.2% of patients reported improvement of ARC. Moreover, this was
      accompanied by a reduced use of symptomatic medication. Adherence to treatment
      was estimated at 96.8%. In general, both patients and specialists exhibited a
      positive attitude towards five-grass pollen tablet treatment. Conclusion: ARC
      patients treated with five-grass pollen tablet showed favourable levels of HRQoL
      and treatment satisfaction, with concomitant improvements in ARC and symptomatic
      medication use, which translated into high levels of treatment adherence and a
      positive attitude towards five-grass pollen tablet.

PMID- 29225658
TI  - Intraspecific eye color variability in birds and mammals: a recent evolutionary
      event exclusive to humans and domestic animals.
AB  - Background: Human populations and breeds of domestic animals are composed of
      individuals with a multiplicity of eye (= iris) colorations. Some wild birds and
      mammals may have intraspecific eye color variability, but this variation seems to
      be due to the developmental stage of the individual, its breeding status, and/or
      sexual dimorphism. In other words, eye colour tends to be a species-specific
      trait in wild animals, and the exceptions are species in which individuals of the
      same age group or gender all develop the same eye colour. Domestic animals, by
      definition, include bird and mammal species artificially selected by humans in
      the last few thousand years. Humans themselves may have acquired a diverse
      palette of eye colors, likewise in recent evolutionary time, in the Mesolithic or
      in the Upper Paleolithic. Presentation of the hypothesis: We posit two previously
      unrecognized hypotheses regarding eye color variation: 1) eye coloration in wild
      animals of every species tends to be a fixed trait. 2) Humans and domestic animal
      populations, on the contrary, have eyes of multiple colors. Sexual selection has
      been invoked for eye color variation in humans, but this selection mode does not
      easily apply in domestic animals, where matings are controlled by the human
      breeder. Testing the hypothesis: Eye coloration is polygenic in humans. We wish
      to investigate the genetics of eye color in other animals, as well as the
      ecological correlates. Implications of the hypothesis: Investigating the origin
      and function of eye colors will shed light on the reason why some species may
      have either light-colored irises (e.g., white, yellow or light blue) or dark ones
      (dark red, brown or black). The causes behind the vast array of eye colors across
      taxa have never been thoroughly investigated, but it may well be that all
      Darwinian selection processes are at work: sexual selection in humans, artificial
      selection for domestic animals, and natural selection (mainly) for wild animals.

PMID- 29225660
TI  - BRAVE NEW WORLD OF BIOSOCIAL SCIENCE.

PMID- 29225659
TI  - Speed dependent phase shifts and gait changes in cockroaches running on
      substrates of different slipperiness.
AB  - Background: Many legged animals change gaits when increasing speed. In insects,
      only one gait change has been documented so far, from slow walking to fast
      running, which is characterised by an alternating tripod. Studies on some fast
      running insects suggested a further gait change at higher running speeds. Apart
      from speed, insect gaits and leg co-ordination have been shown to be influenced
      by substrate properties, but the detailed effects of speed and substrate on gait
      changes are still unclear. Here we investigate high-speed locomotion and gait
      changes of the cockroach Nauphoeta cinerea, on two substrates of different
      slipperiness. Results: Analyses of leg co-ordination and body oscillations for
      straight and steady escape runs revealed that at high speeds, blaberid
      cockroaches changed from an alternating tripod to a rather metachronal gait,
      which to our knowledge, has not been described before for terrestrial arthropods.
      Despite low duty factors, this new gait is characterised by low vertical
      amplitudes of the centre of mass (COM), low vertical accelerations and presumably
      reduced total vertical peak forces. However, lateral amplitudes and accelerations
      were higher in the faster gait with reduced leg synchronisation than in the
      tripod gait with distinct leg synchronisation. Conclusions: Temporally
      distributed leg force application as resulting from metachronal leg coordination
      at high running speeds may be particularly useful in animals with limited
      capabilities for elastic energy storage within the legs, as energy efficiency can
      be increased without the need for elasticity in the legs. It may also facilitate
      locomotion on slippery surfaces, which usually reduce leg force transmission to
      the ground. Moreover, increased temporal overlap of the stance phases of the legs
      likely improves locomotion control, which might result in a higher dynamic
      stability.

PMID- 29225661
TI  - Maternal nutritional status during pregnancy and infant immune response to
      routine childhood vaccinations.
AB  - To systematically review the association between maternal nutritional status in
      pregnancy and infant immune response to childhood vaccines. We reviewed
      literature on maternal nutrition during pregnancy, fetal immune system and
      vaccines and possible relationships. Thereafter, we undertook a systematic review
      of the literature of maternal nutritional status and infant vaccine response,
      extracted relevant information, assessed quality of the nine papers identified
      and present findings in a narrative format. From limited evidence of average
      quality, intrauterine nutrition deficiency could lead to functional deficit in
      the infant's immune function; child vaccine response may thus be negatively
      affected by maternal malnutrition. Response to childhood vaccination may be
      associated with fetal and early life environment; evaluation of programs should
      take this into account.

PMID- 29225662
TI  - Increased accuracy of starch granule type quantification using mixture
      distributions.
AB  - Background: The proportion of granule types in wheat starch is an important
      characteristic that can affect its functionality. It is widely accepted that
      granule types are either large, disc-shaped A-type granules or small, spherical B
      type granules. Additionally, there are some reports of the tiny C-type granules.
      The differences between these granule types are due to its carbohydrate
      composition and crystallinity which is highly, but not perfectly, correlated with
      the granule size. A majority of the studies that have considered granule types
      analyse them based on a size threshold rather than chemical composition. This is
      understandable due to the expense of separating starch into different types.
      While the use of a size threshold to classify granule type is a low-cost measure,
      this results in misclassification. We present an alternative, statistical method
      to quantify the proportion of granule types by a fit of the mixture distribution,
      along with an R package, a web based app and a video tutorial for how to use the
      web app to enable its straightforward application. Results: Our results show that
      the reliability of the genotypic effects increase approximately 60% using the
      proportions of the A-type and B-type granule estimated by the mixture
      distribution over the standard size-threshold measure. Although there was a
      marginal drop in reliability for C-type granules. The latter is likely due to the
      low observed genetic variance for C-type granules. Conclusions: The determination
      of the proportion of granule types from size-distribution is better achieved by
      using the mixing probabilities from the fit of the mixture distribution rather
      than using a size-threshold.

PMID- 29225663
TI  - High-throughput detection of antioxidants in mulberry fruit using correlations
      between high-resolution mass and activity profiles of chromatographic fractions.
AB  - Background: Plant extracts contain a huge variety of pharmacologically active
      substances. Conventionally, various chromatographic methods must be applied
      several times to purify functional compounds to measure their functional
      activity. However, conventional purification methods are time-consuming and
      expensive due to the laborious purification process. Recently, a high-throughput
      discovery method that replaces such time-consuming purification processes was
      introduced; this method uses 15 T ultra-high-resolution Fourier transform ion
      cyclotron resonance mass spectrometry (15 T FT-ICR MS) and a high-throughput
      screening method. This 15 T FT-ICR MS provides unparalleled resolution and sub
      ppm accuracy in mass measurements, while simultaneously detecting multiple
      compounds without separation. The high-throughput, simultaneous multi-component
      discovery method known as Scaling of Correlations between Activity and Mass
      Profiles (SCAMP) was used to detect functional compounds in a plant extract. We
      validated the performance of SCAMP using 33 fractions from antioxidant-rich
      mulberry ethyl acetate extract and known standard antioxidants. Results: The
      mulberry fruit was first separated into 33 fractions by LC and analyzed using
      high-resolution mass spectrometry. The antioxidative strength of the 33 fractions
      and standard antioxidants was measured. To validate the efficiency of this
      antioxidant discovery method, correlations between the antioxidation activity
      profile and changes in mass intensity of components within the 33 fractions were
      calculated to provide relative scores for the antioxidant candidate list.
      Enrichment curves and area under the curve (AUC) values were then calculated to
      compare the performance of the methods. Using this improved scoring method, five
      strong antioxidants, chlorogenic acid (14.2 ng), dihydoxy quercetin (46.2 ng),
      rutin (154.0 ng), quercetin (71.7 ng) and luteolin (3.5 ng) in 2 kg mulberry
      fruit, were found within the top 20 candidates. Conclusions: We calculated AUCs
      in order to compare scoring methods quantitatively. Scoring systems were compared
      and calculated AUCs, where the AUCs for new scoring systems (0.98 and 0.99) were
      higher than the previously used correlation coefficient (AUC = 0.89). Using the
      new scoring algorithms, we successfully enriched thirteen unknown strong
      antioxidant candidates in addition to known antioxidants, methyl syringin and
      naringenin (3.5 ng) in mulberry extract. Targeted purification of these unknown
      candidates will significantly reduce purification time and labor.

PMID- 29225664
TI  - Load balancing for multi-threaded PDES of stochastic reaction-diffusion in
      neurons.
AB  - Stochastic simulation of chemical reactions and diffusion in a neuron helps to
      provide a realistic view of the molecular dynamics within a neuron. We developed
      a multi-threaded PDES simulator, Neuron Time Warp-Multi Thread, suitable for the
      stochastic simulation of reaction and diffusion in a neuron. In this paper we
      make use of Q-Learning and Simulated Annealing to determine the parameters for a
      dynamic load balancing algorithm and for dynamic window control. During the
      simulation, the runtime statistics of each thread are collected and used to
      determine the execution time of the simulation. Based upon this assessment,
      workload is migrated from the most overloaded threads to the most under-load
      ones. As the results for a calcium wave model show, both approaches can improve
      the execution time for small simulations by up to 31% (Q-Learning) and 19% (SA).
      The simulated annealing approach is more suitable for larger populations,
      decreasing execution time by 41%.

PMID- 29225666
TI  - CMOS Active Pixel Sensors as energy-range detectors for proton Computed
      Tomography.
AB  - Since the first proof of concept in the early 70s, a number of technologies has
      been proposed to perform proton CT (pCT), as a means of mapping tissue stopping
      power for accurate treatment planning in proton therapy. Previous prototypes of
      energy-range detectors for pCT have been mainly based on the use of scintillator
      based calorimeters, to measure proton residual energy after passing through the
      patient. However, such an approach is limited by the need for only a single
      proton passing through the energy-range detector in a read-out cycle. A novel
      approach to this problem could be the use of pixelated detectors, where the
      independent read-out of each pixel allows to measure simultaneously the residual
      energy of a number of protons in the same read-out cycle, facilitating a faster
      and more efficient pCT scan. This paper investigates the suitability of CMOS
      Active Pixel Sensors (APSs) to track individual protons as they go through a
      number of CMOS layers, forming an energy-range telescope. Measurements performed
      at the iThemba Laboratories will be presented and analysed in terms of
      correlation, to confirm capability of proton tracking for CMOS APSs.

PMID- 29225667
TI  - Interactive K-Means Clustering Method Based on User Behavior for Different
      Analysis Target in Medicine.
AB  - Clustering algorithm as a basis of data analysis is widely used in analysis
      systems. However, as for the high dimensions of the data, the clustering
      algorithm may overlook the business relation between these dimensions especially
      in the medical fields. As a result, usually the clustering result may not meet
      the business goals of the users. Then, in the clustering process, if it can
      combine the knowledge of the users, that is, the doctor's knowledge or the
      analysis intent, the clustering result can be more satisfied. In this paper, we
      propose an interactive K-means clustering method to improve the user's
      satisfactions towards the result. The core of this method is to get the user's
      feedback of the clustering result, to optimize the clustering result. Then, a
      particle swarm optimization algorithm is used in the method to optimize the
      parameters, especially the weight settings in the clustering algorithm to make it
      reflect the user's business preference as possible. After that, based on the
      parameter optimization and adjustment, the clustering result can be closer to the
      user's requirement. Finally, we take an example in the breast cancer, to testify
      our method. The experiments show the better performance of our algorithm.

PMID- 29225668
TI  - Advanced Image Enhancement Method for Distant Vessels and Structures in Capsule
      Endoscopy.
AB  - This paper proposes an advanced method for contrast enhancement of capsule
      endoscopic images, with the main objective to obtain sufficient information about
      the vessels and structures in more distant (or darker) parts of capsule
      endoscopic images. The proposed method (PM) combines two algorithms for the
      enhancement of darker and brighter areas of capsule endoscopic images,
      respectively. The half-unit weighted-bilinear algorithm (HWB) proposed in our
      previous work is used to enhance darker areas according to the darker map content
      of its HSV's component V. Enhancement of brighter areas is achieved thanks to the
      novel threshold weighted-bilinear algorithm (TWB) developed to avoid overexposure
      and enlargement of specular highlight spots while preserving the hue, in such
      areas. The TWB performs enhancement operations following a gradual increment of
      the brightness of the brighter map content of its HSV's component V. In other
      words, the TWB decreases its averaged weights as the intensity content of the
      component V increases. Extensive experimental demonstrations were conducted, and,
      based on evaluation of the reference and PM enhanced images, a gastroenterologist
      (O.H.) concluded that the PM enhanced images were the best ones based on the
      information about the vessels, contrast in the images, and the view or visibility
      of the structures in more distant parts of the capsule endoscopy images.

PMID- 29225665
TI  - Evolution and Clinical Translation of Drug Delivery Nanomaterials.
AB  - With the advent of technology, the role of nanomaterials in medicine has grown
      exponentially in the last few decades. The main advantage of such materials has
      been exploited in drug delivery applications, due to their effective targeting
      that in turn reduces systemic toxicity compared to the conventional routes of
      drug administration. Even though these materials offer broad flexibility based on
      targeting tissue, disease, and drug payload, the demand for more effective yet
      highly biocompatible nanomaterial-based drugs is increasing. While
      therapeutically improved and safe materials have been introduced in nanomedicine
      platforms, issues related to their degradation rates and bio-distribution still
      exist, thus making their successful translation for human use very challenging.
      Researchers are constantly improving upon novel nanomaterials that are safer and
      more effective not only as therapeutic agents but as diagnostic tools as well,
      making the research in the field of nanomedicine ever more fascinating. In this
      review stress has been made on the evolution of nanomaterials that have been
      approved for clinical applications by the United States Food and Drug
      Administration Agency (FDA).

PMID- 29225669
TI  - Self-Regulation Principles Underlying Risk Perception and Decision Making within
      the Context of Genomic Testing.
AB  - Advances in theory and research on self-regulation and decision-making processes
      have yielded important insights into how cognitive, emotional, and social
      processes shape risk perceptions and risk-related decisions. We examine how self
      regulation theory can be applied to inform our understanding of decision-making
      processes within the context of genomic testing, a clinical arena in which
      individuals face complex risk information and potentially life-altering
      decisions. After presenting key principles of self-regulation, we present a
      genomic testing case example to illustrate how principles related to risk
      representations, approach and avoidance motivations, emotion regulation,
      defensive responses, temporal construals, and capacities such as numeric
      abilities can shape decisions and psychological responses during the genomic
      testing process. We conclude with implications for using self-regulation theory
      to advance science within genomic testing and opportunities for how this research
      can inform further developments in self-regulation theory.

PMID- 29225670
TI  - Weighed down by stigma: How weight-based social identity threat contributes to
      weight gain and poor health.
AB  - Weight stigma is pervasive, and a number of scholars argue that this profound
      stigma contributes to the negative effects of weight on psychological and
      physical health. Some lay individuals and health professionals assume that
      stigmatizing weight can actually motivate healthier behaviors and promote weight
      loss. However, as we review, weight stigma is consistently associated with poorer
      mental and physical health outcomes. In this article we propose a social identity
      threat model elucidating how weight stigma contributes to weight gain and poorer
      mental and physical health among overweight individuals. We propose that weight
      based social identity threat increases physiological stress, undermines self
      regulation, compromises psychological health, and increases the motivation to
      avoid stigmatizing domains (e.g., the gym) and escape the stigma by engaging in
      unhealthy weight loss behaviors. Given the prevalence of overweight and obesity
      in the US, weight stigma thus has the potential to undermine the health and
      wellbeing of millions of Americans.

PMID- 29225672
TI  - The corridor consult.

PMID- 29225671
TI  - Tourette syndrome and other neurodevelopmental disorders: a comprehensive review.
AB  - Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric
      condition in which motor manifestations are often accompanied by comorbid
      conditions that impact the patient's quality of life. In the DSM-5, TS belongs to
      the "neurodevelopmental disorders" group, together with other neurodevelopmental
      conditions, frequently co-occurring. In this study, we searched the PubMed
      database using a combination of keywords associating TS and all
      neurodevelopmental diagnoses. From 1009 original reports, we identified 36
      studies addressing TS and neurodevelopmental comorbidities. The available
      evidence suggests the following: (1) neurodevelopmental comorbidities in TS are
      the rule, rather than the exception; (2) attention deficit/hyperactivity disorder
      (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD
      or/and learning disorder) to a more complex phenotype (TS + autism spectrum
      disorder). We conclude that a prompt diagnosis and a detailed description of TS
      comorbidities are necessary not only to understand the aetiological basis of
      neurodevelopmental disorders but also to address specific rehabilitative and
      therapeutic approaches.

PMID- 29225673
TI  - Update on hepatitis C and implications for pregnancy.
AB  - Mother-to-child transmission of hepatitis C virus infection occurs in a
      significant minority of cases and the diagnosis, treatment and cure of hepatitis
      C virus infection with direct acting antivirals prior to pregnancy can eliminate
      this risk in almost all cases. Women with hepatitis C virus infection have
      increased risks of adverse events in pregnancy and poor perinatal outcomes for
      their children, although the contribution of hepatitis C virus per se is
      difficult to determine. Altering the mode of delivery does not reduce mother to
      child transmission of hepatitis C virus infection, although avoidance of fetal
      scalp electrodes and other potential high risk procedures is recommended during
      pregnancy and delivery. Breast feeding has not been demonstrated to be a risk for
      mother-to-child transmission and avoidance of breast feeding is not recommended,
      although breast feeding with cracked or bleeding nipples is generally avoided.
      Safety of the currently available hepatitis C virus antivirals in pregnancy and
      breastfeeding has not yet been established.

PMID- 29225674
TI  - A review of the structure and training pathways for obstetric medicine physicians
      in Australia and New Zealand.
AB  - In recent decades, women with significant medical conditions have increasingly
      chosen to become pregnant. This has broadened and intensified the interface
      between obstetrics and internal medicine, a collaboration which has always needed
      cooperation but which increasingly demands open discussion and planning to ensure
      optimal outcomes for mother and fetus. The aims of this article are to describe
      the state of obstetric medicine practice in Australia and New Zealand, including
      its history and development, the training and education curriculum, organisation
      of its service delivery, and potential opportunities for research and
      collaboration.

PMID- 29225675
TI  - Pregnancy and myeloproliferative neoplasms : A retrospective monocentric cohort.
AB  - Background: The most frequent myeloproliferative neoplasms are essential
      thrombocythemia and chronic myelogenous leukemia, which usually manifests with
      thrombocytosis. Only essential thrombocythemia is associated with morbidity
      during pregnancy (recurrent miscarriages, intrauterine fetal death, small for
      gestational age and preeclampsia). The aim of this paper is to describe outcomes
      of pregnancy in women with myeloproliferative neoplasms seen at a single academic
      institution. Methods: Data were collected retrospectively from 2002 to 2015.
      Descriptive analyses were performed. Results: Eighteen pregnancies in 13 patients
      and 17 births were identified. One patient had recurrent miscarriages. There were
      two intrauterine fetal deaths, three small for gestational age linked to vascular
      placenta pathology and one preeclampsia. All of these mothers harbored JAK2V617F
      mutation. Two out of three patients with small for gestational age developed a
      venous thrombosis in the two years following delivery. Conclusion: Thrombocytosis
      associated with myeloproliferative neoplasms should be considered as a risk
      factor for maternal and fetal complications.

PMID- 29225676
TI  - Association between insulin resistance and preeclampsia in obese non-diabetic
      women receiving metformin.
AB  - Objectives: To examine whether the reduced incidence of preeclampsia in non
      diabetic obese pregnant women treated with metformin is mediated by changes in
      insulin resistance. Methods: This was a secondary analysis of obese pregnant
      women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were
      measured in 384 of the 400 women who participated in the MOP trial. Homeostasis
      model assessment of insulin resistance (HOMA-IR) was compared in the metformin
      and placebo groups and in those that developed preeclampsia versus those that did
      not develop preeclampsia. Results: At 28 weeks, median HOMA-IR was significantly
      lower in the metformin group. Logistic regression analysis demonstrated that
      there was a significant contribution in the prediction of preeclampsia from
      maternal history of chronic hypertension and gestational weight gain, but not
      HOMA-IR either at randomisation (p = 0.514) or at 28 weeks (p = 0.643).
      Conclusions: Reduced incidence of preeclampsia in non-diabetic obese pregnant
      women treated with metformin is unlikely to be due to changes in insulin
      resistance.

PMID- 29225677
TI  - Maternal sepsis: Opportunity for improvement.

PMID- 29225678
TI  - Pregnancy in women with Klippel-Trenaunay syndrome: Report of three pregnancies
      in a single patient and review of literature.
AB  - Klippel-Trenaunay syndrome is characterised by vascular abnormality which
      increases the risk of thromboembolism and haemorrhage. Physiological changes in
      pregnancy pose an increased risk to these complications. Being an uncommon
      disorder, there is limited literature about the management of women with
      pregnancy and Klippel-Trenaunay syndrome. We report in detail two of three
      pregnancies in a woman with Klippel-Trenaunay syndrome who had repeated episodes
      of haematochezia leading to anaemia, managed with Argon laser Photo-Coagulation
      in pregnancy and also reviewed the complications and the management of pregnant
      women with Klippel-Trenaunay syndrome.

PMID- 29225679
TI  - Relapsed Hodgkin's lymphoma in pregnancy: A case review.
AB  - Hodgkin's lymphoma is rarely diagnosed in pregnancy, occurring in 1:6000
      deliveries. However, improvements in survival and the use of less gonadotoxic
      treatments have increased the number of Hodgkin's lymphoma survivors becoming
      pregnant. Both de novo and relapsed Hodgkin's lymphoma in pregnancy pose
      difficult decisions for both clinicians and patients. This review discusses
      important diagnostic and treatment considerations of relapsed Hodgkin's lymphoma
      in pregnancy. We discuss a difficult case which illustrates these particular
      dilemmas and suggests the evidence behind different modalities of investigation
      and management.

PMID- 29225680
TI  - Presumed acute fatty liver of pregnancy following influenza A hepatitis.
AB  - Acute fatty liver of pregnancy is a rare mitochondrial hepatopathy characterised
      by microvesicular fatty infiltration, and is believed to be due to impaired fatty
      acid oxidation. Hepatitis following influenza virus infection is uncommon. Rarely
      influenza virus infection may be complicated by Reye's syndrome, another hepatic
      microvesicular fat disease. A case of influenza A hepatitis in third trimester of
      pregnancy, followed by the evelopment of presumed acute fatty liver of pregnancy
      is described in this report and a potential mechanism why this may have occurred
      is discussed.

PMID- 29225681
TI  - Successful pregnancy in the context of previously undiagnosed chronic lymphocytic
      leukaemia: A case report and literature review.
AB  - An asymptomatic 36-year-old woman presented with significantly elevated white
      blood cells (165.9 * 109/L) at antenatal booking, in her first pregnancy. Further
      investigations revealed the diagnosis of chronic lymphocytic leukaemia with
      monoallelic deletion of chromosome 13q14. She was supported and monitored through
      out pregnancy, without treatment, and delivered a healthy baby boy at term with
      no complications and is currently being followed up by the haem-oncology team.

PMID- 29225682
TI  - Frontal lobe meningioma mimicking preeclampsia: A case study.
AB  - We report a case of a left frontal lobe meningioma presenting in a woman with
      proteinuric preeclampsia in her first term pregnancy. The patient had a
      background of antepartum migraines that resolved in the second trimester of
      pregnancy. Postpartum, she required urgent surgery and sustained convulsions
      after surgery. She had no residual disease and has had another successful
      pregnancy. This case highlights the importance of cerebral imaging in the context
      of an atypical clinical course of preeclampsia. Although headaches are common in
      pregnancy and usually benign, other, more serious, diagnoses should be considered
      with atypical headaches, a change in the nature of the headache, and headaches
      that persist despite appropriate treatment. A full neurological examination
      including fundoscopy to exclude papilloedema should be performed and abnormal
      findings require further investigation.

PMID- 29225683
TI  - Concurrent maternal and fetal tachyarrhythmia in pregnancy.
AB  - The occurrence of a maternal and fetal tachyarrhythmia together in pregnancy is
      exceedingly rare. We report a case of a persistent fetal atrial ectopic
      tachycardia occurring in conjunction with a maternal atrial tachycardia with left
      ventricular systolic dysfunction. Amiodarone was effective in treating both
      maternal and fetal arrhythmias.

PMID- 29225684
TI  - Colon cancer presenting as pseudo-obstruction during pregnancy - A case report.
AB  - The incidence of colorectal cancer in pregnancy is between 0.002 and 0.008%.
      Diagnosis is often delayed as symptoms of colorectal cancer can mimic as common
      complaints of pregnancy. We present the case of a 29-year-old with a history of
      chronic constipation who presented in the second trimester with abdominal pain,
      inability to tolerate anything orally and no bowel movement in more than three
      weeks. Non-contrast MRI at presentation failed to show an obstructing mass.
      Patient was treated conservatively for presumed pseudo-obstruction secondary to
      worsening constipation from chronic ondansetron use and pregnancy. After four
      days without clinical improvement, she had a colonoscopy that revealed a
      completely obstructing sigmoid mass, which biopsies confirmed was a primary
      colorectal adenocarcinoma. The patient underwent a total abdominal colectomy. She
      was referred to medical oncology and began adjuvant chemotherapy consisting of 5
      fluorouracil, leucovorin and oxaloplatin four weeks post-operatively.

PMID- 29225685
TI  - Retromammary fat, axillary and arm metastases from a retroperitoneal
      leiomyosarcoma: report of a case with an indolent behaviour.
AB  - Leiomyosarcomas are sarcomas that originate within smooth muscle cells and
      generally occur in older patients. These tumours account for 10% of all soft
      tissue sarcomas. Metastases occur most commonly to the lungs, kidneys, and liver.
      Cutaneous metastases may also occur but are usually a very rare and late event.
      We present a case of a 46-year-old woman who developed subcutaneous metastasis to
      the axilla, arm and breast after surgical resection of the primary tumour. The
      patient maintained controlled disease with surgical resections and clinical
      follow-up, initiating chemotherapy one year after the diagnosis of metastatic
      disease.

PMID- 29225686
TI  - Prognostic value of a patient-reported functional score versus physician-reported
      Karnofsky Performance Status Score in brain metastases.
AB  - Introduction: Our aim was to investigate the added prognostic value of a patient
      reported functional outcome score over Karnofsky Performance Status (KPS) in
      patients with non-small-cell lung cancers (NSCLC) with brain metastases.
      Materials and methods: The baseline data are from a prospective cohort study
      involving 140 consecutive patients presenting at our institute. A patient
      reported performance status (PRPS) was obtained by summing the physical- and role
      functioning scale scores of the EORTC QLQ C30 questionnaire. Nested cox
      proportional hazards models predicting survival were developed including both KPS
      and PRPS (full model), KPS only (KPS Model), and PRPS only (PRPS model). The
      incremental value of the addition of KPS or PRPS was ascertained using the
      likelihood ratio test, model adequacy index and integrated discrimination
      Improvement (IDI). Results: PRPS was an independent and statistically significant
      prognostic factor and had only a moderate degree of agreement with KPS. All
      models showed nearly the same discrimination and calibration accuracy, but the
      likelihood ratio test comparing the full model to the KPS model was significant
      (L.R. Chi2 = 5.34, p = 0.02). Model adequacy index for the KPS model was 85%
      versus 95% for the PRPS model. IDI when comparing the KPS model to the full model
      was 0.0279, while it was 0.008 for the PRPS model versus the Full model.
      Conclusions: Use of patient-reported functional outcomes like PRPS can provide
      the same prognostic information as KPS in patients of NSCLC with brain
      metastases. Highlights: Patient-reported functional status (PRPS) has a moderate
      degree of agreement with KPS.PRPS is an independent and significant predictor of
      survival in brain metastases.PRPS can replace KPS without loss of prognostic
      information.

PMID- 29225687
TI  - A different surgical approach for cardiophrenic lymph node resection in advanced
      ovarian cancer.
AB  - Objective: To describe the surgical technique of a subxiphoid approach to remove
      cardiophrenic lymph nodes in women with advanced ovarian cancer. Materials and
      methods: The first step is to dissect and separate the anterior insertions of the
      diaphragm at the xiphoid appendix. Thus, the parietal peritoneum and the upper
      fibres of the transversus abdominis muscle are incised. Then, the anteroinferior
      mediastinum is identified and dissected. Diaphragmatic deinsertion may be
      extended 5-7 cm laterally to the xiphoid appendix following the inferior costal
      margin according with the localization of the enlarged lymph nodes. Thus, the
      dissection of the anterolateral cardiophrenic space allows the identification of
      both pleura. In addition, the vertical dissection of the anterior cardiophrenic
      space allows the removal of enlarged lymph nodes. However, it is important to
      bear in mind at this time that the unintentional opening of the pleura is
      possible. To reduce this risk, a careful dissection of the anterior cardiophrenic
      fat tissue is essential. Moreover, a careful dissection will avoid damage at the
      left phrenic nerve as well as the left pericardiophrenic artery and vein. After
      removing the cardiophrenic fat tissue, the diaphragm is sutured at the lower
      costal margin by using separated stiches of absorbable 2-0 suture. Conclusion:
      The subxiphoid approach to resect cardiophrenic lymph nodes is a feasible
      surgical technique. In addition, it reduces the possibility of opening the
      pleural cavity, while avoiding a diaphragmatic incision, in comparison with the
      standard trans-diaphragmatic surgical approach.

PMID- 29225690
TI  - Do we need regional guidelines for breast cancer management in the MENA region?
      MENA Breast Cancer Guidelines project.
AB  - Purpose: Breast cancer is the most common cancer among females worldwide in
      general and in the Middle East and the North African region (MENA region) in
      particular. Management of breast cancer in the MENA region faces a lot of
      challenges, which include younger age at presentation, aggressive behaviour, lack
      of national breast screening programmes and lack of reliable data registries as
      well as socioeconomic factors. These factors make applying the international
      guidelines for breast cancer management very challenging. The aim of this project
      is to explore the need for a regional breast cancer guideline as well as to
      screen the clinical practice of breast cancer management in the MENA region.
      Methodology: Three web-based designed surveys were sent to more than 600
      oncologists in the MENA region from the period of August 2013 to October 2014.
      Full descriptive data and information regarding the application of international
      breast cancer guidelines were collected. The software was using the IP address to
      prevent duplication of collected data. Descriptive analysis and results were
      shown as numbers and percentages. Results: During the period of the survey, 104
      oncologists responded, representing around an 11% response rate. The majority of
      replies came from Egypt (59 responses (59%)), followed by Saudi Arabia (ten
      responses (9.6%)). Fifty-one per cent of responders had more than ten years of
      experience, and further 31.7% had 5-10 years of experience. Seventy-four per cent
      were working in governmental hospitals, which is our target sector. There was a
      major defect in having a genetic counsel unit (78.8% declared an absence of this
      service), presence of a national breast screening programme (55.8% declared an
      absence of this service), performing sentinel lymph node biopsy (43.3% declared
      an absence of this service). The need for regional guidelines for the management
      of breast cancer was agreed upon by 90.6% of responders. Conclusion: There is a
      clear need to improve the management of breast cancer in the MENA region.
      Creating a national breast screening programme and a reliable database is
      essential. A regional guideline is required to establish the best possible
      management of breast cancer according to the patients and disease specification
      as well as the regional socioeconomic factors and facilities available. There is
      also a need to improve clinical research that meets the region's needs.

PMID- 29225689
TI  - Acute myeloid leukaemia at an early age: Reviewing the interaction between
      pesticide exposure and KMT2A-rearrangement.
AB  - Acute myeloid leukaemia (AML) in early childhood is characterised by a high
      frequency of recurrent genomic aberrations associated with distinct myeloid
      subtypes, clinical outcomes and pathogenesis. Genomic instability is the first
      step of pathogenic mechanism in early childhood AML. A sum of adverse events is
      necessary to the development of infant AML (i-AML), which includes latency of
      biochemical-molecular and cellular effects. Inherited genetic susceptibility
      associated with exposures to biotransformation substances can modulate the risk
      of DNA damage and it is a very important piece in the pathogenic puzzle. In this
      review, we have aimed to explore the chain of events in the time-points of the
      natural history of i-AML, which includes maternal exposures during pregnancy, the
      speculations about the formation of somatic mutations during foetal life and the
      secondary genomic aberrations associated with i-AML. The modulation of risk
      conferred by xenobiotic metabolism's genes variants is the bottom line of the
      pathogenic process. Since we have conducted observational and molecular
      investigations in early childhood leukaemia, the data focused here is based on
      Brazilian findings with summarised results of our experience with epidemiological
      and molecular studies in early-age leukaemia.

PMID- 29225688
TI  - Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti
      cancer agents.
AB  - Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline
      antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in
      the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in
      anti-cancer therapy, especially in combination with conventional anti-cancer
      treatments since they are able to sensitise tumour cells to a variety of drugs,
      potentiating the therapeutic activity. Thus far, clinical results are mostly in
      favour of the repurposing of CQ. However, over 30 clinical studies are still
      evaluating the activity of both CQ and HCQ in different cancer types and in
      combination with various standard treatments. Interestingly, CQ and HCQ exert
      effects both on cancer cells and on the tumour microenvironment. In addition to
      inhibition of the autophagic flux, which is the most studied anti-cancer effect
      of CQ and HCQ, these drugs affect the Toll-like receptor 9, p53 and CXCR4-CXCL12
      pathway in cancer cells. In the tumour stroma, CQ was shown to affect the tumour
      vasculature, cancer-associated fibroblasts and the immune system. The evidence
      reviewed in this paper indicates that both CQ and HCQ deserve further clinical
      investigations in several cancer types. Special attention about the drug (CQ
      versus HCQ), the dose and the schedule of administration should be taken in the
      design of new trials.

PMID- 29225691
TI  - History of the development of radiotherapy in Latin America.
AB  - Radiotherapy was the first nonsurgical treatment for malignant tumours and
      represents one of the oldest disciplines of oncology. In Latin America, as in
      many parts of the world, the history of modern oncology begins with the
      implementation of radiation therapy facilities. The development of radiotherapy
      in Latin America was possible thanks to the seminal work of radiation oncologists
      in different countries. As a large territory, there is a need to implement modern
      facilities and equipment, but unfortunately there are disparities in the access
      and quality of radiotherapy services across Latin America and even within
      individual countries. In this review, we describe the history, challenges and
      success in the implementation of radiotherapy and the frustration caused by the
      lack of facilities in several Latin American countries.

PMID- 29225693
TI  - Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: a single
      centre analysis of toxicity and clinical outcome.
AB  - Objectives: The current standard of care for patients with metastatic prostate
      cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without
      anti-androgen and chemotherapy. The aim of this study was to define the role of a
      local radiotherapy (RT) treatment in the mPCa setting. Methods: We
      retrospectively reviewed data of patients with PCa and bone oligometastases at
      diagnosis treated in our institution with ADT followed by cytoreductive prostate
      RT with or without RT on metastases. Biochemical and clinical failure (BF, CF),
      overall survival (OS) and RT-toxicity were assessed. Results: We identified 22
      patients treated with ADT and external-beam RT on primary between June 2008 and
      March 2016. All of them but four were also treated for bone metastases. RT on
      primary with moderately and extremely hypofractionated regimes started after 10.3
      months (3.9-51.7) from ADT. After a median follow-up of 26.4 months (10.3-55.5),
      20 patients are alive. Twelve patients showed BF after a median time of 23 months
      (14.5-104) and CF after a median of 23.6 months (15.3-106.1) from the start of
      ADT. Three patients became castration resistant, starting a new therapy; median
      time to castration resistance was 31.03 months (range: 29.9-31.5 months).
      According to the Radiation Therapy Oncology Group/European Organization for
      Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute
      grade 3 genitourinary toxicity. No late grade >2 adverse events were observed.
      Conclusion: Prostate RT in oligometastatic patients is safe and offers long
      lasting local control. When compared to ADT alone, RT on primary seems to improve
      biochemical control and long-term survival; however, this hypothesis should be
      investigated in prospective studies. Further research is warranted.

PMID- 29225692
TI  - Recent advances in radiation oncology.
AB  - Radiotherapy (RT) is very much a technology-driven treatment modality in the
      management of cancer. RT techniques have changed significantly over the past few
      decades, thanks to improvements in engineering and computing. We aim to highlight
      the recent developments in radiation oncology, focusing on the technological and
      biological advances. We will present state-of-the-art treatment techniques,
      employing photon beams, such as intensity-modulated RT, volumetric-modulated arc
      therapy, stereotactic body RT and adaptive RT, which make possible a highly
      tailored dose distribution with maximum normal tissue sparing. We will analyse
      all the steps involved in the treatment: imaging, delineation of the tumour and
      organs at risk, treatment planning and finally image-guidance for accurate tumour
      localisation before and during treatment delivery. Particular attention will be
      given to the crucial role that imaging plays throughout the entire process. In
      the case of adaptive RT, the precise identification of target volumes as well as
      the monitoring of tumour response/modification during the course of treatment is
      mainly based on multimodality imaging that integrates morphological, functional
      and metabolic information. Moreover, real-time imaging of the tumour is essential
      in breathing adaptive techniques to compensate for tumour motion due to
      respiration. Brief reference will be made to the recent spread of particle beam
      therapy, in particular to the use of protons, but also to the yet limited
      experience of using heavy particles such as carbon ions. Finally, we will analyse
      the latest biological advances in tumour targeting. Indeed, the effectiveness of
      RT has been improved not only by technological developments but also through the
      integration of radiobiological knowledge to produce more efficient and
      personalised treatment strategies.

PMID- 29225695
TI  - When populism takes over the delivery of health care: Venezuela.
AB  - Adequate and modern health care is not available in Venezuela at this moment. A
      humanitarian crisis of post war dimensions is currently rampant and afflicting
      all Venezuelans alike. The delivery and availability of cancer care is severely
      limited and inadequate. No funding is available as populist measures,
      mismanagement, pillaging, corruption, lack of forethought and expertise have
      brought the country into severe economic collapse and political turmoil.

PMID- 29225694
TI  - Non-small cell lung cancer treatment (r)evolution: ten years of advances and more
      to come.
AB  - Diagnostic and treatment algorithms in non-small cell lung cancer (NSCLC) are
      evolving at a never-before-seen pace. Histological subtyping to maximise
      treatment efficacy and avoid toxicity has marked the beginning of the revolution,
      opening the way to molecular characterisation to guide genomically driven
      treatments with targeted agents, led by Epidermal Growth Factor Receptor (EGFR)
      and Anaplastic Lymphoma Kinase (ALK) inhibitors. More recently, agents against
      the Program Death 1 receptor (PD-1) and ligand 1 (PD-L1) have entered the
      clinical arena, offering new hope to NSCLC patients, although several
      uncertainties remain to be elucidated. Here, we review the most clinically
      relevant advances in the diagnosis and treatment of NSCLC in the past decade.

PMID- 29225696
TI  - Colorectal cancer: towards new challenges and concepts of preventive healthcare.
AB  - Colorectal cancer (CRC) holds the woeful record of being the most preventable but
      least prevented type of cancer. Although healthy lifestyles and screening
      programs associated to early polyp removal greatly reduce CRC incidence and CRC
      related death, the overall lack of information and of effective preventive
      policies is promoting an overwhelming global escalation of this disease.
      Moreover, new challenges such as the increasing occurrence of aggressive CRC in
      young adults highlight underlying changes not only in the incidence but also in
      the nature of this disease. In this scenario, CRC prevention should also undergo
      a significant transformation, embracing not only individual initiatives but also
      issues of social and international relevance. The nascent network of countries
      surrounding the Mediterranean basin (COLOMED, the COLOrectal cancer MEDiterranean
      network) serves as a paradigm of international cooperation aimed at broadening
      scientific collaboration and promoting effective health policies in CRC research
      and prevention.

PMID- 29225697
TI  - Comparative evaluation of Populus variants total sugar release and structural
      features following pretreatment and digestion by two distinct biological systems.
AB  - Background: Populus natural variants have been shown to realize a broad range of
      sugar yields during saccharification, however, the structural features
      responsible for higher sugar release from natural variants are not clear. In
      addition, the sugar release patterns resulting from digestion with two distinct
      biological systems, fungal enzymes and Clostridium thermocellum, have yet to be
      evaluated and compared. This study evaluates the effect of structural features of
      three natural variant Populus lines, which includes the line BESC standard, with
      respect to the overall process of sugar release for two different biological
      systems. Results: Populus natural variants, SKWE 24-2 and BESC 876, showed higher
      sugar release from hydrothermal pretreatment combined with either enzymatic
      hydrolysis or Clostridium thermocellum fermentation compared to the Populus
      natural variant, BESC standard. However, C. thermocellum outperformed the fungal
      cellulases yielding 96.0, 95.5, and 85.9% glucan plus xylan release from SKWE 24
      2, BESC 876, and BESC standard, respectively. Among the feedstock properties
      evaluated, cellulose accessibility and glycome profiling provided insights into
      factors that govern differences in sugar release between the low recalcitrant
      lines and the BESC standard line. However, because this distinction was more
      apparent in the solids after pretreatment than in the untreated biomass,
      pretreatment was necessary to differentiate recalcitrance among Populus lines.
      Glycome profiling analysis showed that SKWE 24-2 contained the most loosely bound
      cell wall glycans, followed by BESC 876, and BESC standard. Additionally, lower
      molecular weight lignin may be favorable for effective hydrolysis, since C.
      thermocellum reduced lignin molecular weight more than fungal enzymes across all
      Populus lines. Conclusions: Low recalcitrant Populus natural variants, SKWE 24-2
      and BESC 876, showed higher sugar yields than BESC standard when hydrothermal
      pretreatment was combined with biological digestion. However, C. thermocellum was
      determined to be a more robust and effective biological catalyst than a
      commercial fungal cellulase cocktail. As anticipated, recalcitrance was not
      readily predicted through analytical methods that determined structural
      properties alone. However, combining structural analysis with pretreatment
      enabled the identification of attributes that govern recalcitrance, namely
      cellulose accessibility, xylan content in the pretreated solids, and non
      cellulosic glycan extractability.

PMID- 29225698
TI  - Predicting the most appropriate wood biomass for selected industrial
      applications: comparison of wood, pulping, and enzymatic treatments using
      fluorescent-tagged carbohydrate-binding modules.
AB  - Background: Lignocellulosic biomass will progressively become the main source of
      carbon for a number of products as the Earth's oil reservoirs disappear.
      Technology for conversion of wood fiber into bioproducts (wood biorefining)
      continues to flourish, and access to reliable methods for monitoring modification
      of such fibers is becoming an important issue. Recently, we developed a simple,
      rapid approach for detecting four different types of polymer on the surface of
      wood fibers. Named fluorescent-tagged carbohydrate-binding module (FTCM), this
      method is based on the fluorescence signal from carbohydrate-binding modules
      based probes designed to recognize specific polymers such as crystalline
      cellulose, amorphous cellulose, xylan, and mannan. Results: Here we used FTCM to
      characterize pulps made from softwood and hardwood that were prepared using Kraft
      or chemical-thermo-mechanical pulping. Comparison of chemical analysis (NREL
      protocol) and FTCM revealed that FTCM results were consistent with chemical
      analysis of the hemicellulose composition of both hardwood and softwood samples.
      Kraft pulping increased the difference between softwood and hardwood surface
      mannans, and increased xylan exposure. This suggests that Kraft pulping leads to
      exposure of xylan after removal of both lignin and mannan. Impact of enzyme
      cocktails from Trichoderma reesei (Celluclast 1.5L) and from Aspergillus sp.
      (Carezyme 1000L) was investigated by analysis of hydrolyzed sugars and by FTCM.
      Both enzymes preparations released cellobiose and glucose from pulps, with the
      cocktail from Trichoderma being the most efficient. Enzymatic treatments were not
      as effective at converting chemical-thermomechanical pulps to simple sugars,
      regardless of wood type. FTCM revealed that amorphous cellulose was the primary
      target of either enzyme preparation, which resulted in a higher proportion of
      crystalline cellulose on the surface after enzymatic treatment. FTCM confirmed
      that enzymes from Aspergillus had little impact on exposed hemicelluloses, but
      that enzymes from the more aggressive Trichoderma cocktail reduced hemicelluloses
      at the surface. Conclusions: Overall, this study indicates that treatment with
      enzymes from Trichoderma is appropriate for generating crystalline cellulose at
      fiber surface. Applications such as nanocellulose or composites requiring
      chemical resistance would benefit from this enzymatic treatment. The milder
      enzyme mixture from Aspergillus allowed for removal of amorphous cellulose while
      preserving hemicelluloses at fiber surface, which makes this treatment
      appropriate for new paper products where surface chemical responsiveness is
      required.

PMID- 29225699
TI  - 3-Hydroxypropionaldehyde production from crude glycerol by Lactobacillus
      diolivorans with enhanced glycerol uptake.
AB  - Background: In their quest for sustainable development and effective management
      of greenhouse gas emissions, our societies pursue a shift away from fossil-based
      resources towards renewable resources. With 95% of our current transportation
      energy being petroleum based, the application of alternative, carbon-neutral
      products-among them biodiesel-is inevitable. In order to enhance the cost
      structure of biodiesel biorefineries, the valorization of the crude glycerol
      waste stream into high-value platform chemicals is of major importance. Results:
      The purpose of this study is the production of 3-hydroxypropionaldehyde (3-HPA)
      from biodiesel-derived crude glycerol by Lactobacillus diolivorans. Particular
      focus is given on overcoming potential limitations of glycerol transport into the
      cell, in order to use the cells' total glycerol dehydratase capability towards
      the formation of 3-HPA as the main product. Recombinant overexpression of the
      endogenous glycerol uptake facilitating protein PduF results in a significant
      increase of glycerol conversion by a factor of 1.3. Concomitantly, glycerol
      dehydratase activity increased from initially 1.70 +/- 0.03 U/mg protein to 2.23
      +/- 0.11 U/mg protein. With this approach, an average productivity of 4.8 g3
      HPA/(gCDM h) yielding up to 35.9 g/L 3-HPA and 0.91 mol3-HPA/molGlycerol have
      been obtained. Conclusion: Lactobacillus diolivorans proves to be a valuable cell
      factory for the utilization of crude glycerol delivering high-value C3 chemicals
      like 3-HPA, 1,3-propanediol (1,3-PDO) and 3-hydroxypropionic acid (3-HP).
      Enhancing the glycerol influx into the cell by genetic engineering was successful
      paving the way towards the commercial production of 3-HPA.

PMID- 29225700
TI  - Unusual variants of mycosis fungoides.
AB  - Conventional presentations of mycosis fungoides may be diagnostically
      challenging, particularly in light of the controversial boundaries defining the
      disease. Variant presentations of this cutaneous T-cell lymphoma add a further
      layer of complexity, requiring a sophisticated and informed perspective when
      evaluating lymphoid infiltrates in the skin. Herein we discuss well-defined (WHO
      EORTC) variants pagetoid reticulosis, granulomatous slack skin and
      folliculotropic mycosis fungoides as well as less well-defined
      morphologic/architectural variants, and divergent immunohistochemical
      presentations of this typically indolent T-cell lymphoproliferative disease.

PMID- 29225701
TI  - Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing
      factor (CNF) colonize laboratory macaques.
AB  - Background: Many Escherichia coli strains are considered to be a component of the
      normal flora found in the human and animal intestinal tracts. While most E. coli
      strains are commensal, some strains encode virulence factors that enable the
      bacteria to cause intestinal and extra-intestinal clinically-relevant infections.
      Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing
      factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular
      differentiation, apoptosis and proliferation. Some commensal and pathogenic pks+
      and cnf+ E. coli strains have been associated with inflammation and cancer in
      humans and animals. Results: In the present study, E. coli strains encoding
      colibactin and CNF were identified in macaque samples. We performed bacterial
      cultures utilizing rectal swabs and extra-intestinal samples from clinically
      normal macaques. A total of 239 E. coli strains were isolated from 266 macaques.
      The strains were identified biochemically and selected isolates were serotyped as
      O88:H4, O25:H4, O7:H7, OM:H14, and OM:H16. Specific PCR for pks and cnf1 gene
      amplification, and phylogenetic group identification were performed on all E.
      coli strains. Among the 239 isolates, 41 (17.2%) were pks+/cnf1-, 19 (7.9%) were
      pks-/cnf1+, and 31 (13.0%) were pks+/cnf1+. One hundred forty-eight (61.9%) E.
      coli isolates were negative for both genes (pks-/cnf1-). In total, 72 (30.1%)
      were positive for pks genes, and 50 (20.9%) were positive for cnf1. No cnf2+
      isolates were detected. Both pks+ and cnf1+ E. coli strains belonged mainly to
      phylogenetic group B2, including B21. Colibactin and CNF cytotoxic activities
      were observed using a HeLa cell cytotoxicity assay in representative isolates.
      Whole genome sequencing of 10 representative E. coli strains confirmed the
      presence of virulence factors and antibiotic resistance genes in rhesus macaque
      E. coli isolates. Conclusions: Our findings indicate that colibactin- and CNF
      encoding E. coli colonize laboratory macaques and can potentially cause clinical
      and subclinical diseases that impact macaque models.

PMID- 29225702
TI  - The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene
      polymorphism on the efficacy of insulin detemir therapy in patients with type 2
      diabetes mellitus.
AB  - Background: Type II diabetes is an important health problem with a complex
      connection to obesity, leading to a broad range of cardiovascular complications.
      Insulin therapy often results in weight gain and does not always ensure adequate
      glycemic control. However, previous studies reported that insulin detemir is an
      efficient long-acting insulin with a weight sparing effect. The aim of this study
      was to determine the association of catechol O-methyltransferase (COMT)
      Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the
      effectiveness of insulin detemir in achieving glucose control and body weight
      control. Participants and methods: This 52-week observational study included 185
      patients with inadequate glycemic control treated with premix insulin analogues,
      which were replaced with insulin aspart and insulin detemir, and 156 healthy
      controls. After DNA isolation from blood samples, genotyping of DBH-1021C/T
      polymorphism (rs1611115) and COMT Val108/158Met polymorphism (rs4680) was
      performed. Results: Our results confirmed that insulin detemir did not lead to
      weight gain. The most significant finding was that A carriers (the combined AG
      and AA genotype) of the COMT Val108/158Met achieved significantly better
      hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No
      association between DBH-1021C/T genotypes and weight and/or glucose control was
      detected in diabetes patients or in healthy control subjects. Conclusions: This
      study showed that the presence of one or two A allele of the COMT Val108/158Met
      was associated with improved glycemic response, and with a better response to
      insulin detemir therapy in patients with type II diabetes, separating them as
      best candidates for detemir therapy.

PMID- 29225703
TI  - Facilitators and barriers to healthy eating in a worksite cafeteria: a
      qualitative study from Nepal.
AB  - Objective: Worksite interventions can serve as a potential platform for
      translating existing knowledge of diabetes prevention and facilitate healthy food
      choices. The study explored perceptions about healthy eating as well as potential
      facilitators and barriers to healthy eating among employees in a wire
      manufacturing factory in Nepal. Methods and materials: We conducted a cross
      sectional exploratory qualitative study in a wire manufacturing industry in
      eastern Nepal. We conducted three focus group discussions (FGDs) with a total of
      26 employees and four in-depth interviews (IDIs) with cafeteria
      operators/managers from a wire manufacturing factory in eastern Nepal. FGDs and
      IDIs were audio-recorded, transcribed verbatim and analysed using the thematic
      method. Results: Most employees defined healthy eating as the consumption of food
      prepared and maintained using hygienic practices and fresh foods in general.
      Major barriers to healthy eating included unavailability of healthy foods,
      difficulty in changing eating habits, the preference for fried foods in Nepali
      culture and the high costs of some healthy foods. The most commonly reported
      facilitator of healthy eating was the availability of affordable healthy food
      options in worksite cafeterias. Conclusion: Availability of healthy food options
      at an affordable price could lead to healthier food choices in the worksite.

PMID- 29225704
TI  - Transcription coupled repair and biased insertion of human retrotransposon L1 in
      transcribed genes.
AB  - Background: L1 retrotransposons inserted within genes in the human genome show a
      strong bias against sense orientation with respect to the gene. One suggested
      explanation for this observation was the possibility that L1 inserted randomly,
      but that there was negative selection against sense-oriented insertions. However,
      multiple studies have now found that de novo and polymorphic L1 insertions, which
      have little opportunity for selection to act, also show the same bias. Results:
      Here we show that the transcription-coupled sub-pathway of nucleotide excision
      repair does not affect the overall rate of insertion of L1 elements, which is in
      contrast with the regulation by the global sub-pathway of nucleotide excision
      repair. The transcription-coupled subpathway does cause a strong bias against
      insertion in the sense orientation relative to genes. Conclusions: This suggests
      that a major portion of the L1 orientation bias might be generated during the
      process of insertion through the action of transcription-coupled nucleotide
      excision repair.

PMID- 29225706
TI  - Comparison of photo- and thermally initiated polymerization-induced self
      assembly: a lack of end group fidelity drives the formation of higher order
      morphologies.
AB  - Polymerization-induced self-assembly (PISA) is an emerging industrially relevant
      technology, which allows the preparation of defined and predictable polymer self
      assemblies with a wide range of morphologies. In recent years, interest has
      turned to photoinitiated PISA processes, which show markedly accelerated reaction
      kinetics and milder conditions, thereby making it an attractive alternative to
      thermally initiated PISA. Herein, we attempt to elucidate the differences between
      these two initiation methods using isothermally derived phase diagrams of a well
      documented poly(ethylene glycol)-b-(2-hydroxypropyl methacrylate) (PEG-b-HPMA)
      PISA system. By studying the influence of the intensity of the light source used,
      as well as an investigation into the thermodynamically favorable morphologies,
      the factors dictating differences in the obtained morphologies when comparing
      photo- and thermally initiated PISA were explored. Our findings indicate that
      differences in a combination of both reaction kinetics and end group fidelity led
      to the observed discrepencies between the two techniques. We find that the loss
      of the end group in photoinitiated PISA drives the formation of higher order
      structures and that a morphological transition from worms to unilamellar vesicles
      could be induced by extended periods of light and heat irradiation. Our findings
      demonstrate that PISA of identical block copolymers by the two different
      initiation methods can lead to structures that are both chemically and
      morphologically distinct.

PMID- 29225707
TI  - How to evaluate the immune status of lung cancer patients before immunotherapy.
AB  - Nowadays, cancer immunotherapy is a promising strategy in solid tumour treatment.
      It has become a breakthrough in achieving long-term survival in many advanced
      cases. The essence of modern immunotherapy is to improve the host antitumour
      immune defence. Currently, it is critically important to determine the biomarkers
      that could be helpful in planning this type of individual therapy. It has turned
      out that an important prognostic factor is the evaluation of inflammatory
      infiltration of the tumour mass, including the characteristics of populations of
      lymphocytes and macrophages, and the expression of suppressive and regulatory
      molecules. For lung cancer, <30% of the tumours are resectable and available for
      a complete microscopic examination. In other cases, the material for the study of
      inflammatory infiltration may be a tumour biopsy, but this is of limited
      importance. A valuable way to evaluate the microenvironment of tumour growth is a
      bronchoalveolar lavage (BAL) fluid examination. In the BAL fluid, the cellular
      and noncellular components determine the specific type of inflammatory response
      in an environment of developing cancer. BAL fluid analysis may be a valuable
      addition to peripheral blood analysis during qualification for modern
      immunomodulatory therapy. Moreover, it is important material to seek biomarkers
      of clinical significance.

PMID- 29225705
TI  - Using bioinformatic and phylogenetic approaches to classify transposable elements
      and understand their complex evolutionary histories.
AB  - In recent years, much attention has been paid to comparative genomic studies of
      transposable elements (TEs) and the ensuing problems of their identification,
      classification, and annotation. Different approaches and diverse automated
      pipelines are being used to catalogue and categorize mobile genetic elements in
      the ever-increasing number of prokaryotic and eukaryotic genomes, with little or
      no connectivity between different domains of life. Here, an overview of the
      current picture of TE classification and evolutionary relationships is presented,
      updating the diversity of TE types uncovered in sequenced genomes. A tripartite
      TE classification scheme is proposed to account for their replicative,
      integrative, and structural components, and the need to expand in vitro and in
      vivo studies of their structural and biological properties is emphasized.
      Bioinformatic studies have now become front and center of novel TE discovery, and
      experimental pursuits of these discoveries hold great promise for both basic and
      applied science.

PMID- 29225708
TI  - Ranges of phenotypic flexibility in healthy subjects.
AB  - Background: A key feature of metabolic health is the ability to adapt upon
      dietary perturbations. A systemic review defined an optimal nutritional challenge
      test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables
      the quantification of all relevant metabolic processes involved in maintaining or
      regaining homeostasis of metabolic health. Furthermore, it was demonstrated that
      quantification of PFT response was more sensitive as compared to fasting markers
      in demonstrating reduced phenotypic flexibility in metabolically impaired type 2
      diabetes subjects. Methods: This study aims to demonstrate that quantification of
      PFT response can discriminate between different states of health within the
      healthy range of the population. Therefore, 100 healthy subjects were enrolled
      (50 males, 50 females) ranging in age (young, middle, old) and body fat
      percentage (low, medium, high), assuming variation in phenotypic flexibility.
      Biomarkers were selected to quantify main processes which characterize phenotypic
      flexibility in response to PFT: flexibility in glucose, lipid, amino acid and
      vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was
      visualized using the "health space" by representing the four processes on the
      health space axes. By quantifying and presenting the study subjects in this
      space, individual phenotypic flexibility was visualized. Results: Using the
      "health space" visualization, differences between groups as well as within groups
      from the healthy range of the population can be easily and intuitively assessed.
      The health space showed a different adaptation to the metabolic PhenFlex test in
      the extremes of the recruited population; persons of young age with low to normal
      fat percentage had a markedly different position in the health space as compared
      to persons from old age with normal to high fat percentage. Conclusion: The
      results of the metabolic PhenFlex test in conjunction with the health space
      reliably assessed health on an individual basis. This quantification can be used
      in the future for personalized health quantification and advice.

PMID- 29225709
TI  - Immunomodulatory Effects of Human Cryopreserved Viable Amniotic Membrane in a Pro
      Inflammatory Environment In Vitro.
AB  - Introduction: Chronic wounds remain a major clinical challenge. Human
      cryopreserved viable amniotic membrane (hCVAM) is among the most successful
      therapies, but the mechanisms of action remain loosely defined. Because proper
      regulation of macrophage behavior is critical for wound healing with biomaterial
      therapies, we hypothesized that hCVAM would positively regulate macrophage
      behavior in vitro, and that soluble factors released from the hCVAM would be
      important for this effect. Materials and Methods: Primary human pro-inflammatory
      (M1) macrophages were seeded directly onto intact hCVAM or cultured in separation
      via transwell inserts (Soluble Factors) in the presence of pro-inflammatory
      stimuli (interferon-gamma and lipopolysaccharide) to simulate the chronic wound
      environment. Macrophages were characterized after 1 and 6 days using multiplex
      gene expression analysis of 37 macrophage phenotype- and angiogenesis-related
      genes via NanoStringTM, and protein content from conditioned media collected at
      days 1, 3 and 6 was analyzed via enzyme linked immunosorbent assays. Results and
      Discussion: Gene expression analysis showed that Soluble Factors promoted
      significant upregulation of pro-inflammatory marker IL1B on day 1 yet
      downregulation of TNF on day 6 compared to the M1 macrophage control. In
      contrast, intact hCVAM, which includes both extracellular matrix, viable cells,
      and soluble factors, promoted downregulation of pro-inflammatory markers TNF,
      CCL5 and CCR7 on day 1 and endothelial receptor TIE1 on day 6, and upregulation
      of the anti-inflammatory marker IL10 on day 6 compared to the M1 Control. Other
      genes related to inflammation and angiogenesis (MMP9, VEGF, SPP1, TGFB1, etc.)
      were differentially regulated between the Soluble Factors and intact hCVAM groups
      at both time points, though they were not expressed at significantly different
      levels compared to the M1 Control. Interestingly, Soluble Factors promoted
      increased secretion of the proinflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha), while direct contact with hCVAM inhibited secretion of TNF, relative
      to the M1 Control. Both Soluble Factors and intact hCVAM inhibited secretion of
      MMP9 and VEGF, pro-inflammatory proteins that are critical for angiogenesis and
      remodeling, compared to the M1 Control, with intact hCVAM having a stronger
      effect. Conclusions: In a simulated pro-inflammatory environment, intact hCVAM
      has distinct anti-inflammatory effects on primary human macrophages, and direct
      macrophage contact with intact hCVAM is required for these effects. These
      findings are important for the design of next generation immunomodulatory
      biomaterials for wound repair and regenerative medicine that may include living
      cells, soluble factors, or a controlled drug delivery system.

PMID- 29225711
TI  - New developments in the pathology of malignant lymphoma. A review of the
      literature published from September-August 2017.

PMID- 29225712
TI  - A Look-Ahead Strategy for Non-Directed Donors in Kidney Paired Donation.
AB  - While there is a growing need for kidney transplants to treat end stage kidney
      disease, the supply of transplantable kidneys is in serious shortage. Kidney
      paired donation (KPD) programs serve as platforms for candidates with willing but
      incompatible donors to assess the possibility of exchanging donors, thus opening
      up new transplant opportunities for these candidates. In recent years, non
      directed (or altruistic) donors (NDDs) have been incorporated into KPD programs
      beginning chains of transplants that benefit many candidates. In such programs,
      making optimal decisions in transplant exchange selection is of critical
      importance. With the aim of improving the selection of chains beginning with an
      NDD, this paper introduces a look-ahead multiple decision strategy to select
      chains, that are easy to extend in the future. Simulation studies are adopted to
      assess performance of this strategy. Taking into account the extensibility of
      chains increases the number of realized transplants.

PMID- 29225713
TI  - Understanding Landmarking and Its Relation with Time-Dependent Cox Regression.
AB  - Time-dependent Cox regression and landmarking are the two most commonly used
      approaches for the analysis of time-dependent covariates in time-to-event data.
      The estimated effect of the time-dependent covariate in a landmarking analysis is
      based on the value of the time-dependent covariate at the landmark time point,
      after which the time-dependent covariate may change value. In this note we derive
      expressions for the (time-varying) regression coefficient of the time-dependent
      covariate in the landmark analysis, in terms of the regression coefficient and
      baseline hazard of the time-dependent Cox regression. These relations are
      illustrated using simulation studies and using the Stanford heart transplant
      data.

PMID- 29225710
TI  - Novel developments in the pathogenesis and diagnosis of extranodal marginal zone
      lymphoma.
AB  - Extranodal marginal zone lymphoma (EMZL), mostly represented by mucosa-associated
      lymphoid tissue (MALT) type, also referred to as MALT lymphoma, is a clinically
      heterogeneous entity within the group of low-grade B cell lymphomas that arises
      in a wide range of different extranodal sites, including the stomach, lung,
      ocular adnexa, and skin. It represents the third most common non-Hodgkin lymphoma
      in the Western world, and the median age of occurrence is around 60 years. One
      characteristic aspect in a subset of EMZL detectable in about 25% of the cases is
      the presence of specific chromosomal translocations involving the genes MALT1 and
      BCL10, which lead to activation of the NF-kappaB signaling pathway. Another
      unique aspect is that several infectious agents, such as Helicobacter pylori in
      the case of gastric EMZL, and autoimmune disorders, like Sjogren syndrome, have
      been implicated in the pathogenesis of this cancer. Recent findings as summarized
      in this review have further improved our understanding of the complex
      pathobiology of this disease and have been essential to better define novel
      treatment strategies. In addition, many of these specific features are currently
      being implemented for the diagnosis of EMZL.

PMID- 29225714
TI  - Incorporating High-Dimensional Exposure Modelling into Studies of Air Pollution
      and Health.
AB  - Performing studies on the risks of environmental hazards on human health requires
      accurate estimates of exposures that might be experienced by the populations at
      risk. Often there will be missing data and in many epidemiological studies, the
      locations and times of exposure measurements and health data do not match. To a
      large extent this will be due to the health and exposure data having arisen from
      completely different data sources and not as the result of a carefully designed
      study, leading to problems of both 'change of support' and 'misaligned data'. In
      such cases, a direct comparison of the exposure and health outcome is often not
      possible without an underlying model to align the two in the spatial and temporal
      domains. The Bayesian approach provides the natural framework for such models;
      however, the large amounts of data that can arise from environmental networks
      means that inference using Markov Chain Monte Carlo might not be computationally
      feasible in this setting. Here we adapt the integrated nested Laplace
      approximation to implement spatio-temporal exposure models. We also propose
      methods for the integration of large-scale exposure models and health analyses.
      It is important that any model structure allows the correct propagation of
      uncertainty from the predictions of the exposure model through to the estimates
      of risk and associated confidence intervals. The methods are demonstrated using a
      case study of the levels of black smoke in the UK, measured over several decades,
      and respiratory mortality.

PMID- 29225715
TI  - Classification of Large-Scale Remote Sensing Images for Automatic Identification
      of Health Hazards: Smoke Detection Using an Autologistic Regression Classifier.
AB  - Remote sensing images from Earth-orbiting satellites are a potentially rich data
      source for monitoring and cataloguing atmospheric health hazards that cover large
      geographic regions. A method is proposed for classifying such images into hazard
      and nonhazard regions using the autologistic regression model, which may be
      viewed as a spatial extension of logistic regression. The method includes a novel
      and simple approach to parameter estimation that makes it well suited to handling
      the large and high-dimensional datasets arising from satellite-borne instruments.
      The methodology is demonstrated on both simulated images and a real application
      to the identification of forest fire smoke.

PMID- 29225716
TI  - N-of-1 Design and Its Applications to Personalized Treatment Studies.
AB  - N-of-1 trial is a type of clinical trial which has been applied in chronic
      recurrent conditions that require long-term non-curative treatment. In this type
      of trials, each patient will be randomly assigned to one of the treatment
      sequences and repeatedly crossed over two or more treatments of interests.
      Through this cross-comparing method (cross-over phase), investigator can identify
      an optimal treatment (medicine or therapy) for the patient and treat the patient
      with the optimal treatment in an extension phase. This design could efficiently
      reduce the placebo effect, which is often seen in clinical trials, and maximize
      the true treatment effect. This type of design has been used in some traditional
      Chinese medicine (TCM) clinical trials lately. However, it brings some challenges
      for collecting and analyzing the data. Research on statistical methodology of
      this type of design is rarely found in the literature. The goal of this research
      is to discuss the application of the N-of-1 design to personalized treatment
      studies. We will demonstrate a real study conducted in TCM and present some
      theoretical and simulation results.

PMID- 29225718
TI  - Strategies for dereplication of natural compounds using high-resolution tandem
      mass spectrometry.
AB  - Complete structural elucidation of natural products is commonly performed by
      nuclear magnetic resonance spectroscopy (NMR), but annotating compounds to most
      likely structures using high-resolution tandem mass spectrometry is a faster and
      feasible first step. The CASMI contest 2016 (Critical Assessment of Small
      Molecule Identification) provided spectra of eighteen compounds for the best
      manual structure identification in the natural products category. High resolution
      precursor and tandem mass spectra (MS/MS) were available to characterize the
      compounds. We used the Seven Golden Rules, Sirius2 and MS-FINDER software for
      determination of molecular formulas, and then we queried the formulas in
      different natural product databases including DNP, UNPD, ChemSpider and REAXYS to
      obtain molecular structures. We used different in-silico fragmentation tools
      including CFM-ID, CSI:FingerID and MS-FINDER to rank these compounds. Additional
      neutral losses and product ion peaks were manually investigated. This manual and
      time consuming approach allowed for the correct dereplication of thirteen of the
      eighteen natural products.

PMID- 29225717
TI  - Feasibility of quantifying SDC2 methylation in stool DNA for early detection of
      colorectal cancer.
AB  - Background: Colorectal cancer (CRC) screening is the most efficient strategy to
      reduce disease-related mortality. Frequent aberrant DNA methylation is known to
      occur in selected genes and early during CRC development, which has emerged as a
      new epigenetic biomarker for early detection of CRC. Previously, we reported that
      we identified that CpG sites of SDC2 were aberrantly methylated in tumor tissues
      of most CRC patients through comprehensive methylation analysis and demonstrated
      a high potential of quantification of SDC2 methylation in blood for early
      detection of colorectal cancer. In this study, we aim to investigate the
      feasibility of quantifying SDC2 methylation in stool DNA for the early detection
      of CRC. The objective of this study was to confirm a high frequency of SDC2
      methylation in tumor tissues at various stages of CRC and investigate the
      feasibility of a quantitative test for SDC2 methylation in fecal DNA by highly
      sensitive and accurate real-time PCR for early detection of CRC. Methods:
      Bisulfite-pyrosequencing assay was performed to measure the SDC2 methylation
      status in tissue samples. For methylation analysis in stool DNA, a highly
      sensitive and accurate method was applied which implements consecutive two rounds
      of PCR consisting of unidirectional linear target enrichment (LTE) of SDC2 and
      quantitative methylation-specific real time PCR (qMSP) for SDC2, named as meSDC2
      LTE-qMSP assay. Its limit of detection was 0.1% methylation (corresponding to ~ 6
      copies in total ~ 6200 genome copies). Results: Positive SDC2 methylation was
      observed in 100% of primary tumors, 90.6% of adenomatous polyps, 94.1% of
      hyperplastic polyps, and 0% of normal tissues. SDC2 methylation level also
      significantly (P < 0.01) increased according to the severity of lesions. In stool
      DNA test for SDC2 methylation by LTE-qMSP comparing CRC patients with various
      stages (I to IV) (n = 50) and precancerous lesions (n = 21) with healthy subjects
      (n = 22), the overall sensitivity was 90.0% for detecting CRC and 33.3% for
      detecting small polyps, with a specificity of 90.9%. Conclusions: Taken together,
      our result indicates that stool DNA-based SDC2 methylation test by LTE-qMSP is a
      potential noninvasive diagnostic tool for early detection of CRC.

PMID- 29225719
TI  - Methane optical density measurements with an integrated path differential
      absorption lidar from an airborne platform.
AB  - We report on an airborne demonstration of atmospheric methane (CH4) measurements
      with an Integrated Path Differential Absorption (IPDA) lidar using an optical
      parametric amplifier (OPA) and optical parametric oscillator (OPO) laser
      transmitter and sensitive avalanche photodiode detector. The lidar measures the
      atmospheric CH4 absorption at multiple, discrete wavelengths near 1650.96 nm. The
      instrument was deployed in the fall of 2015, aboard NASA's DC-8 airborne
      laboratory along with an in-situ spectrometer and measured CH4 over a wide range
      of surfaces and atmospheric conditions from altitudes of 2 km to 13 km. In this
      paper, we will show the results from our flights, compare the performance of the
      two laser transmitters, and identify areas of improvement for the lidar.

PMID- 29225720
TI  - New frontiers in molecular and imaging research on evaluation and diagnosis of
      bladder outlet obstruction in women.
AB  - Purpose: Diagnosis of bladder outlet obstruction (BOO) often presents a challenge
      in female patients. Traditional diagnostic elements such as symptom history and
      urodynamic data are rarely clear cut in women. Therefore, we sought to review the
      current literature on diagnosis of female BOO, focusing on new frontiers in the
      realm of molecular markers and imaging modalities. Recent Findings: In addition
      to fluoroscopy in the setting of videourodynamics, ultrasound and MRI can augment
      the diagnosis and aid in therapeutic planning in certain etiologies of female
      BOO. Furthermore, multiple potential biomarkers (i.e. nerve growth factor,
      prostaglandins, ATP) that have been studied in correlation to BOO in animal
      models as well as human subjects hold promise for diagnostic applications.
      Summary: These novel techniques may augment standard clinical and urodynamic
      evaluation of BOO in females. Future directions include further studies of each
      of these biomarkers in female patients with BOO compared to normal controls to
      test their feasibility as potential screening tools.

PMID- 29225721
TI  - Catalytic Hydrogenation and Hydrodeoxygenation of Furfural over Pt(111): A Model
      System for the Rational Design and Operation of Practical Biomass Conversion
      Catalysts.
AB  - Furfural is a key bioderived platform chemical whose reactivity under hydrogen
      atmospheres affords diverse chemical intermediates. Here, temperature-programmed
      reaction spectrometry and complementary scanning tunneling microscopy (STM) are
      employed to investigate furfural adsorption and reactivity over a Pt(111) model
      catalyst. Furfural decarbonylation to furan is highly sensitive to reaction
      conditions, in particular, surface crowding and associated changes in the
      adsorption geometry: furfural adopts a planar geometry on clean Pt(111) at low
      coverage, tilting at higher coverage to form a densely packed furfural adlayer.
      This switch in adsorption geometry strongly influences product selectivity. STM
      reveals the formation of hydrogen-bonded networks for planar furfural, which
      favor decarbonylation on clean Pt(111) and hydrogenolysis in the presence of
      coadsorbed hydrogen. Preadsorbed hydrogen promotes furfural hydrogenation to
      furfuryl alcohol and its subsequent hydrogenolysis to methyl furan, while
      suppressing residual surface carbon. Furfural chemistry over Pt is markedly
      different from that over Pd, with weaker adsorption over the former affording a
      simpler product distribution than the latter; Pd catalyzes a wider range of
      chemistry, including ring-opening to form propene. Insight into the role of
      molecular orientation in controlling product selectivity will guide the design
      and operation of more selective and stable Pt catalysts for furfural
      hydrogenation.

PMID- 29225723
TI  - Comment on "A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental
      Parkinson's Disease".

PMID- 29225724
TI  - Effects of White Wine Consumption on Weight in Rats: Do Polyphenols Matter?
AB  - Introduction: Effects of white wine and the role of wine polyphenols on weight
      gain in rats of different age were examined in the 4-week-voluntary-consumption
      trial. Methods and Materials: Biochemically characterized standard (low
      polyphenols, W) and macerated (high polyphenolic content, PW) white wines were
      compared. One- and three-month-old Sprague-Dawley male rats (n = 78) were used.
      Each age group was subdivided into water-only-drinking controls (C), W, and PW
      drinking animals. Daily wine and total liquid consumption, food intake, and body
      weight were measured, and energy intake and feed efficiency index were
      calculated. Results: In both age categories, wine-drinking animals consumed less
      food and gained less weight in comparison to C (181 +/- 2, 179 +/- 6, and 201 +/-
      5 in younger animals and 32 +/- 5, 28 +/- 6, and 47 +/- 4 grams in older animals,
      resp.), regardless of wine type. Total energy intake was the lowest in PW
      drinking animals. Conclusion: Wine-drinking animals gained less weight in
      comparison to C, regardless of the wines' polyphenol content. Although our
      results are indicative of the major role of nonphenolic constituents of the wines
      (probably ethanol), the modifying role of wine phenolics on weight gain cannot be
      excluded as the group consuming PW had lower total energy intake than other
      groups.

PMID- 29225722
TI  - Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA
      Damage Response Play a Role?
AB  - Age-related macular degeneration (AMD) is the main reason of blindness in
      developed countries. Aging is the main AMD risk factor. Oxidative stress,
      inflammation and some genetic factors play a role in AMD pathogenesis. AMD is
      associated with the degradation of retinal pigment epithelium (RPE) cells,
      photoreceptors, and choriocapillaris. Lost RPE cells in the central retina can be
      replaced by their peripheral counterparts. However, if they are senescent,
      degenerated regions in the macula cannot be regenerated. Oxidative stress, a main
      factor of AMD pathogenesis, can induce DNA damage response (DDR), autophagy, and
      cell senescence. Moreover, cell senescence is involved in the pathogenesis of
      many age-related diseases. Cell senescence is the state of permanent cellular
      division arrest and concerns only mitotic cells. RPE cells, although quiescent in
      the retina, can proliferate in vitro. They can also undergo oxidative stress
      induced senescence. Therefore, cellular senescence can be considered as an
      important molecular pathway of AMD pathology, resulting in an inability of the
      macula to regenerate after degeneration of RPE cells caused by a factor inducing
      DDR and autophagy. It is too early to speculate about the role of the mutual
      interplay between cell senescence, autophagy, and DDR, but this subject is worth
      further studies.

PMID- 29225725
TI  - Low Glucose Concentrations Induce a Similar Inflammatory Response in Monocytes
      from Type 2 Diabetic Patients and Healthy Subjects.
AB  - This study aims to assess the proinflammatory interleukin 1beta (IL-1beta) and
      anti-inflammatory IL-10 production by monocytes from 38 patients with type 2
      diabetes and 31 controls in different glucose concentrations. Monocytes were
      incubated in low (2.5 mmol/L)-, normal (5.0 mmol/L)-, and high (20 mmol/L)
      glucose conditions in the presence and absence of lipopolysaccharide (LPS).
      Monocytes from both patients and controls only produced a significant increase in
      IL-1beta in low-glucose conditions (p < 0.01), and this phenomenon was amplified
      in the presence of LPS, while it was not seen in normal- or high-glucose
      conditions, not even in the presence of LPS stimulation. There was no increase in
      IL-10 production by monocytes from either diabetic patients or controls using
      whatever glucose concentrations, except when treated with LPS in normal-glucose
      conditions. These findings seem to suggest that low-glucose conditions induce an
      inflammatory response in monocytes in all individuals, as an intrinsic capacity
      of this cell line. On the other hand, monocytes only retain their anti
      inflammatory ability in response to known inflammatory stimuli such as LPS, under
      normal-glucose concentrations. In conclusion, human monocytes express an
      inflammatory pattern in low-glucose conditions in vitro. This response could
      contribute to explaining the higher cardiovascular risk induced by hypoglycemia
      in diabetic patients.

PMID- 29225726
TI  - Incidence, Diagnosis, and Treatment of Cardiac Toxicity from Trastuzumab in
      Patients with Breast Cancer.
AB  - Purpose of review: Treatment with trastuzumab is a cornerstone of human epidermal
      growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but
      carries an unfortunate risk of toxicity to the cardiovascular system. Here we
      review recent findings on trastuzumab-associated cardiotoxicity, focusing on its
      incidence, diagnosis, and treatment. Recent findings: Screening with multigated
      acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac
      function prior to and during trastuzumab therapy. Because trastuzumab-induced
      cardiotoxicity is typically reversible, cessation of trastuzumab and/or
      administration of first line heart failure agents effectively restores cardiac
      function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough
      that the risk-benefit ratio still weighs in favor of its use in the vast majority
      of patients with HER2+ breast cancer. Summary: An improved understanding of the
      pathophysiology underlying trastuzumab-induced cardiotoxicity and the
      identification of patients at highest risk will allow us to continue to safely
      administer trastuzumab in patients with breast cancer.

PMID- 29225727
TI  - The genomic study of an environmental isolate of Scedosporium apiospermum shows
      its metabolic potential to degrade hydrocarbons.
AB  - Crude oil contamination of soils and waters is a worldwide problem, which has
      been actively addressed in recent years. Sequencing genomes of microorganisms
      involved in the degradation of hydrocarbons have allowed the identification of
      several promoters, genes, and degradation pathways of these contaminants. This
      knowledge allows a better understanding of the functional dynamics of microbial
      degradation. Here, we report a first draft of the 44.2 Mbp genome assembly of an
      environmental strain of the fungus Scedosporium apiospermum. The assembly
      consisted of 178 high-quality DNA scaffolds with 1.93% of sequence repeats
      identified. A total of 11,195 protein-coding genes were predicted including a
      diverse group of gene families involved in hydrocarbon degradation pathways like
      dioxygenases and cytochrome P450. The metabolic pathways identified in the genome
      can potentially degrade hydrocarbons like chloroalkane/alkene, chorocyclohexane,
      and chlorobenzene, benzoate, aminobenzoate, fluorobenzoate, toluene, caprolactam,
      geraniol, naphthalene, styrene, atrazine, dioxin, xylene, ethylbenzene, and
      polycyclic aromatic hydrocarbons. The comparison analysis between this strain and
      the previous sequenced clinical strain showed important differences in terms of
      annotated genes involved in the hydrocarbon degradation process.

PMID- 29225728
TI  - The complete genome sequence of the rumen bacterium Butyrivibrio hungatei MB2003.
AB  - Butyrivibrio hungatei MB2003 was isolated from the plant-adherent fraction of
      rumen contents from a pasture-grazed New Zealand dairy cow, and was selected for
      genome sequencing in order to examine its ability to degrade plant
      polysaccharides. The genome of MB2003 is 3.39 Mb and consists of four replicons;
      a chromosome, a secondary chromosome or chromid, a megaplasmid and a small
      plasmid. The genome has an average G + C content of 39.7%, and encodes 2983
      putative protein-coding genes. MB2003 is able to use a variety of monosaccharide
      substrates for growth, with acetate, butyrate and formate as the principal
      fermentation end-products, and the genes encoding these metabolic pathways have
      been identified. MB2003 is predicted to encode an extensive repertoire of CAZymes
      with 78 GHs, 7 CEs, 1 PL and 78 GTs. MB2003 is unable to grow on xylan or pectin,
      and its role in the rumen appears to be as a utilizer of monosaccharides,
      disaccharides and oligosaccharides made available by the degradative activities
      of other bacterial species.

PMID- 29225729
TI  - Draft genome sequence of Bacillus velezensis 2A-2B strain: a rhizospheric
      inhabitant of Sporobolus airoides (Torr.) Torr., with antifungal activity against
      root rot causing phytopathogens.
AB  - A Bacillus velezensis strain from the rhizosphere of Sporobolus airoides (Torr.)
      Torr., a grass in central-north Mexico, was isolated during a biocontrol of
      phytopathogens scrutiny study. The 2A-2B strain exhibited at least 60% of growth
      inhibition of virulent isolates of phytopathogens causing root rot. These
      phytopathogens include Phytophthora capsici, Fusarium solani, Fusarium oxysporum
      and Rhizoctonia solani. Furthermore, the 2A-2B strain is an indolacetic acid
      producer, and a plant inducer of PR1, which is an induced systemic resistance
      related gene in chili pepper plantlets. Whole genome sequencing was performed to
      generate a draft genome assembly of 3.953 MB with 46.36% of GC content, and a N50
      of 294,737. The genome contains 3713 protein coding genes and 89 RNA genes.
      Moreover, comparative genome analysis revealed that the 2A-2B strain had the
      greatest identity (98.4%) with Bacillus velezensis.

PMID- 29225731
TI  - Blind Source Separation - Based Motion Detector for Sub-Micrometer, Periodic
      Displacement in Ultrasonic Imaging.
AB  - Sub-micrometer, periodic motion detection using blind source separation (BSS) via
      principal component analysis (PCA) is presented in the context of magnetomotive
      ultrasound (MMUS) imaging and Shearwave Dispersion Ultrasound Vibrometry (SDUV).
      In MMUS, an oscillating external magnetic field displaces tissue loaded with
      superparamagnetic iron oxide (SPIO) particles, whereas in SDUV, periodic tissue
      motion is induced using acoustic radiation force (ARF) to measure visco-elastic
      properties. BSS motion detection performance in MMUS imaging and SDUV was
      compared against frequency-phase locked (FPL) and normalized cross-correlation
      (NCC) motion detectors, respectively, in silico and in experimental phantoms.
      Parametric MMUS phantom images constructed using the BSS method had nearly twice
      the SNR of the corresponding images constructed using FPL method when a 0.043 mm
      or smaller kernel size was used. In FEM models of SDUV, the error in the BSS
      estimated viscoelastic properties of simulated materials was < 10%, whereas the
      error was > 20% using NCC when the simulated SNR was 15 dB. In a calibrated
      elasticity phantom, the amplitude of the motion was <= 0.5 MUm for a scanner
      power level <= 20%. The median percent error in BSS-derived shear modulus of the
      phantom was -6.8%, -1.55%, -17.11% for power level of 20%, 15%, and 10%,
      respectively. The corresponding NCC-derived errors were 29.90%, 127.1%, and
      244.70%. These results suggest the relevance of using BSS for the detection of
      sub-micrometer, periodic motion in MMUS and SDUV imaging, particularly when SNR
      is less than 15 dB and/or induced displacements are less than 0.5 MUm.

PMID- 29225730
TI  - Draft genome sequences of Bradyrhizobium shewense sp. nov. ERR11T and
      Bradyrhizobium yuanmingense CCBAU 10071T.
AB  - The type strain of the prospective 10.1601/nm.30737 sp. nov. ERR11T, was isolated
      from a nodule of the leguminous tree Erythrina brucei native to Ethiopia. The
      type strain 10.1601/nm.1463 10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+10071 T,
      was isolated from the nodules of Lespedeza cuneata in Beijing, China. The genomes
      of ERR11T and 10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+10071 T were sequenced
      by DOE-JGI and deposited at the DOE-JGI genome portal as well as at the European
      Nucleotide Archive. The genome of ERR11T is 9,163,226 bp in length and has 102
      scaffolds, containing 8548 protein-coding and 86 RNA genes. The
      10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+10071 T genome is arranged in 108
      scaffolds and consists of 8,201,522 bp long and 7776 protein-coding and 85 RNA
      genes. Both genomes contain symbiotic genes, which are homologous to the genes
      found in the complete genome sequence of 10.1601/nm.24498
      10.1601/strainfinder?urlappend=%3Fid%3DUSDA+110 T. The genes encoding for
      nodulation and nitrogen fixation in ERR11T showed high sequence similarity with
      homologous genes found in the draft genome of peanut-nodulating 10.1601/nm.27386
      10.1601/strainfinder?urlappend=%3Fid%3DLMG+26795 T. The nodulation genes nolYA
      nodD2D1YABCSUIJ-nolO-nodZ of ERR11T and
      10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+10071 T are organized in a similar
      way to the homologous genes identified in the genomes of
      10.1601/strainfinder?urlappend=%3Fid%3DUSDA+110 T, 10.1601/nm.25806
      10.1601/strainfinder?urlappend=%3Fid%3DUSDA+4 and 10.1601/nm.1462
      10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+05525. The genomes harbor hupSLCFHK
      and hypBFDE genes that code the expression of hydrogenase, an enzyme that helps
      rhizobia to uptake hydrogen released by the N2-fixation process and genes
      encoding denitrification functions napEDABC and norCBQD for nitrate and nitric
      oxide reduction, respectively. The genome of ERR11T also contains nosRZDFYLX
      genes encoding nitrous oxide reductase. Based on multilocus sequence analysis of
      housekeeping genes, the novel species, which contains eight strains formed a
      unique group close to the 10.1601/nm.25806 branch. Genome Average Nucleotide
      Identity (ANI) calculated between the genome sequences of ERR11T and closely
      related sequences revealed that strains belonging to 10.1601/nm.25806 branch
      (10.1601/strainfinder?urlappend=%3Fid%3DUSDA+4 and
      10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+15615), were the closest strains to
      the strain ERR11T with 95.2% ANI. Type strain ERR11T showed the highest DDH
      predicted value with 10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+15615 (58.5%),
      followed by 10.1601/strainfinder?urlappend=%3Fid%3DUSDA+4 (53.1%). Nevertheless,
      the ANI and DDH values obtained between ERR11T and
      10.1601/strainfinder?urlappend=%3Fid%3DCCBAU+15615 or
      10.1601/strainfinder?urlappend=%3Fid%3DUSDA+4 were below the cutoff values (ANI
      >= 96.5%; DDH >= 70%) for strains belonging to the same species, suggesting that
      ERR11T is a new species. Therefore, based on the phylogenetic analysis, ANI and
      DDH values, we formally propose the creation of 10.1601/nm.30737 sp. nov. with
      strain ERR11T (10.1601/strainfinder?urlappend=%3Fid%3DHAMBI+3532
      T=10.1601/strainfinder?urlappend=%3Fid%3DLMG+30162 T) as the type strain.

PMID- 29225732
TI  - Laparoscopic complete mesocolic excisions for colonic cancer in the last decade:
      Five-year survival in a single centre.
AB  - AIM: To analyse clinical and long-term oncologic results after laparoscopic
      complete mesocolic excision (CME) for colonic cancer over a 10-year period.
      METHODS: Consecutive patients who received laparoscopic CME at our hospital from
      2007 to 2017 were prospectively registered and retrospectively analysed. In
      total, 341 patients were included with tumour-nodal-metastasis (TNM) stages 0
      III. RESULTS: The mean age of the patients was 71.9 years. The median length of
      stay was 5 d. The mean lymph node harvest was 17.8. The mortality rate was 1.2%.
      Fifteen patients were reoperated on for anastomotic leaks. The local recurrence
      rate was 2.3%. Five-year TTR and cancer-specific survival CSS were 83.1% and
      90.3%. The location of the tumour was not a significant variable for survival in
      unadjusted and adjusted survival analysis. TNM stage and anastomotic leaks were
      significant variables with respect to survival. CONCLUSION: Laparoscopic CME
      results in acceptable complication rates and long-term oncologic results. It is
      important to avoid anastomotic leaks because of their negative effect on
      survival.

PMID- 29225733
TI  - Colorectal surgeon consensus with diverticulitis clinical practice guidelines.
AB  - AIM: To determine the application of clinical practice guidelines for the current
      management of diverticulitis and colorectal surgeon specialist consensus in
      Australia and New Zealand. METHODS: A survey was distributed to 205 colorectal
      surgeons in Australia and New Zealand, using 22 hypothetical clinical scenarios.
      RESULTS: The response rate was 102 (50%). For 19 guideline-based scenarios, only
      11 (58%) reached consensus (defined as > 70% majority opinion) and agreed with
      guidelines; while 3 (16%) reached consensus and did not agree with guidelines.
      The remaining 5 (26%) scenarios showed community equipoise (defined as less
      than/equal to 70% majority opinion). These included diagnostic imaging where CT
      scan was contraindicated, management options in the failure of conservative
      therapy for complicated diverticulitis, surgical management of Hinchey grade 3,
      proximal extent of resection in sigmoid diverticulitis and use of oral mechanical
      bowel preparation and antibiotics for an elective colectomy. The consensus areas
      not agreeing with guidelines were management of simple diverticulitis, management
      following the failure of conservative therapy in uncomplicated diverticulitis and
      follow-up after an episode of complicated diverticulitis. Fifty-percent of
      rural/regional based surgeons would perform an urgent sigmoid colectomy in failed
      conservative therapy of diverticulitis compared to only 8% of surgeons city-based
      (Fisher's exact test P = 0.016). In right-sided complicated diverticulitis, a
      greater number of those in practice for more than ten years would perform an
      ileocecal resection and ileocolic anastomosis (79% vs 41%, P < 0.0001).
      CONCLUSION: While there are areas of consensus in diverticulitis management,
      there are areas of community equipoise for future research, potentially in the
      form of RCTs.

PMID- 29225734
TI  - PDRG1 at the interface between intermediary metabolism and oncogenesis.
AB  - PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the
      p53 and DNA damage-regulated gene 1 (PDRG1) gene exhibits maximal expression in
      the testis and minimal levels in the liver. Increased expression has been
      detected in several tumor cells and in response to genotoxic stress. High
      throughput studies identified the PDRG1 protein in a variety of macromolecular
      complexes involved in processes that are altered in cancer cells. For example,
      this oncogene has been found as part of the RNA polymerase II complex, the
      splicing machinery and nutrient sensing machinery, although its role in these
      complexes remains unclear. More recently, the PDRG1 protein was found as an
      interaction target for the catalytic subunits of methionine adenosyltransferases.
      These enzymes synthesize S-adenosylmethionine, the methyl donor for, among
      others, epigenetic methylations that occur on the DNA and histones. In fact,
      downregulation of S-adenosylmethionine synthesis is the first functional effect
      directly ascribed to PDRG1. The existence of global DNA hypomethylation, together
      with increased PDRG1 expression, in many tumor cells highlights the importance of
      this interaction as one of the putative underlying causes for cell
      transformation. Here, we will review the accumulated knowledge on this oncogene,
      emphasizing the numerous aspects that remain to be explored.

PMID- 29225735
TI  - Effects of energy drinks on the cardiovascular system.
AB  - Throughout the last decade, the use of energy drinks has been increasingly looked
      upon with caution as potentially dangerous due to their perceived strong
      concentration of caffeine aside from other substances such as taurine, guarana,
      and L-carnitine that are largely unknown to the general public. In addition, a
      large number of energy drink intoxications have been reported all over the world
      including cases of seizures and arrhythmias. In this paper, we focus on the
      effect of energy drinks on the cardiovascular system and whether the current
      ongoing call for the products' sales and regulation of their contents should
      continue.

PMID- 29225736
TI  - Randomized study comparing incidence of radial artery occlusion post-percutaneous
      coronary intervention between two conventional compression devices using a novel
      air-inflation technique.
AB  - AIM: To compare post-percutaneous coronary intervention (PCI) radial artery
      occlusion (RAO) incidence between two conventional radial artery compression
      devices using a novel air-inflation technique. METHODS: One hundred consecutive
      patients post-PCI were randomized 1:1 to Safeguard or TR band compression
      devices. Post-radial sheath removal, each compression device was inflated with
      additional 2 mL of air above index bleeding point during air-filled device
      application and gradually down-titrated accordingly. RAO was defined as absence
      of Doppler flow signal performed at 24 h and at 6 wk post-PCI. Patients with
      missing data were excluded. Statistical significance was defined as P < 0.05.
      RESULTS: All patients had 6F radial sheath inserted. No significant differences
      were observed between Safeguard Radial (n = 42) vs TR band (n = 42) in terms of
      age (63 +/- 11 years vs 67 +/- 11 years), clinical presentation (electives, n =
      18 vs n = 16; acute coronary syndrome, n = 24 vs n = 26) and total procedural
      heparin (7778 +/- 2704 IU vs 7825 +/- 2450 IU). RAO incidence was not
      significantly different between groups at 24 h (2% vs 0%, P = 0.32) and 6 wk (0%,
      both). CONCLUSION: Safeguard Radial and TR band did not demonstrate significant
      between-group differences in short-term RAO incidence. Lack of evidence of RAO in
      all post-PCI patients at 6 wk follow-up, regardless of radial compression device
      indicate advantage of using the novel and pragmatic air-inflation technique.
      Further work is required to more accurately confirm these findings.

PMID- 29225737
TI  - Comparison of seldinger and trocar techniques in the percutaneous treatment of
      hydatid cysts.
AB  - AIM: To comparatively evaluate Seldinger and Trocar techniques in the
      percutaneous treatment of hydatid disease. METHODS: Trocar and Seldinger
      techniques were used for 49 and 56 cysts, respectively, among 106 hydatid cysts
      in 88 patients. The number of males and females were 22 and 66, respectively with
      a mean age of 44.9 years (range, 15-87). Follow-up studies included cyst
      diameter, cyst contents, and morphological changes in the cyst wall, local
      recurrence, and secondary invasion, using ultrasound, computerized tomography and
      chest X-rays. RESULTS: The positive criteria of healing were a decrease in cyst
      diameter, progressive solidification of the cyst contents, and disappearance of
      the cyst. Local recurrence was defined as an increase in the cyst diameter and
      contents, and appearance of daughter cysts in the primary cavity, while secondary
      dissemination was defined as the appearance of new cysts outside the treated
      cyst. Mean duration of follow-up was 19.23 mo (range, 18-26 mo). Follow-up
      results demonstrated that no significant differences were present between the
      Trocar and Seldinger techniques in the percentage of decrease in the cyst volume,
      rate of early complications, local recurrence and secondary dissemination (P =
      0.384, 0.069, 0.215 and 0.533, respectively). CONCLUSION: There are no
      differences between the Seldinger and Trocar techniques that gain entry to the
      cyst cavity in terms of the efficacy of the treatment and the rates of early and
      late complications.

PMID- 29225738
TI  - Naso-jejunal tube insertion - interface between radiology and endoscopy.
AB  - A survey was performed to identify the practice associated with endoscopic
      placement of naso-jejunal (NJ) tubes. We had a total of 236 responses, of which
      228 responded to the frequency of requesting X-ray after placing NJ tubes. The
      responses suggested that there was a strong variation in the practice. The
      practice was independent on clinicians' area of interest, hospital setting or
      experience in endoscopy. Currently there are no accepted guidelines on this.
      Hence, we advise hospitals to have robust local guidelines until there is
      internationally agreed consensus.

PMID- 29225739
TI  - Beyond the neonate: how do anesthetics affect the fetal brain?

PMID- 29225740
TI  - Glycemic control in acute illness.
AB  - Hyperglycemia is commonly observed in critical illness. A landmark large
      randomized controlled trial (RCT) reported that the incidence of hyperglycemia
      (blood glucose concentration > 108 mg/dl) was as high as 97.2% in critically ill
      patients. During the past two decades, a number of RCTs and several meta-analyses
      and network meta-analyses have been conducted to determine the optimal target for
      acute glycemic control. The results of those studies suggest that serum glucose
      concentration would be better to be maintained between 144 and 180 mg/dl.
      Although there have been studies showing an association of hypoglycemia with
      worsened clinical outcomes, a causal link has yet to be confirmed. Nonetheless,
      some researchers are of the view that the data suggest even mild hypoglycemia
      should be avoided in critically ill patients. Since acutely ill patients who
      receive insulin infusion are at a higher risk of hypoglycemia, a reliable devices
      for measuring blood glucose concentrations, such as an arterial blood gas
      analyzer, should be used frequently. Acute glycemic control in patients with
      premorbid hyperglycemia is a novel issue. Available literature suggests that
      blood glucose concentrations considered to be desirable and/or safe in non
      diabetic critically ill patients might not be desirable in patients with
      diabetes. Moreover, the optimal target for acute blood glucose control may be
      higher in critically ill patients with premorbid hyperglycemia. Further study is
      required to assess optimal blood glucose control in acutely ill patients with
      premorbid hyperglycemia.

PMID- 29225741
TI  - What is the proper ventilation strategy during laparoscopic surgery?
AB  - The main stream of intraabdominal surgery has changed from laparotomy to
      laparoscopy, but anesthetic care for laparoscopic surgery is challenging for
      clinicians, because pneumoperitoneum might aggravate respiratory mechanics and
      arterial oxygenation. The authors reviewed the literature regarding ventilation
      strategies that reduce deleterious pulmonary physiologic changes during
      pneumoperitoneum for laparoscopic surgery under general anesthesia and make
      appropriate recommendations.

PMID- 29225742
TI  - Introduction of a pilot study.
AB  - A pilot study asks whether something can be done, should the researchers proceed
      with it, and if so, how. However, a pilot study also has a specific design
      feature; it is conducted on a smaller scale than the main or full-scale study. In
      other words, the pilot study is important for improvement of the quality and
      efficiency of the main study. In addition, it is conducted in order to assess the
      safety of treatment or interventions and recruitment potentials, examine the
      randomization and blinding process, increase the researchers' experience with the
      study methods or medicine and interventions, and provide estimates for sample
      size calculation. This review discusses with a focus on the misconceptions and
      the ethical aspect of a pilot study. Additionally how to interpret the results of
      a pilot study is also introduced in this review.

PMID- 29225743
TI  - Comparison of the clinical performance of the modified Marsh model for propofol
      between underweight and normal-weight patients with Crohn's disease.
AB  - Background: The aim of this retrospective study was to compare the clinical
      performance of the modified Marsh model for propofol between underweight and
      normal-weight patients with Crohn's disease. Methods: The medical records of 50
      patients who underwent elective surgery for Crohn's disease were reviewed
      retrospectively. Propofol and remifentanil were administered using target effect
      site concentration (Ce)-controlled infusion with the modified Marsh and Minto
      models. Target Ce values of propofol were adjusted within a range of 2.5-3 ug/ml
      to maintain a bispectral index (BIS) value of less than 60 during anesthesia
      maintenance. Dosages of anesthetic agents administered during surgery were
      compared between underweight and normal-weight patients. The infusion profiles of
      patients were applied as inputs to calculate the Ce values in the Schnider model.
      Results: The total midazolam and remifentanil dosages required for underweight
      patients were higher than those required for normal-weight patients to maintain
      BIS values at less than 60 within a target propofol Ce range of 2.5-3 ug/ml.
      Simulation results suggested that the Schnider model may be an appropriate
      pharmacokinetic model for target-controlled infusion in underweight patients, as
      the clearance was consistently higher in the Schnider model than the modified
      Marsh model, particularly in underweight patients. Conclusions: The modified
      Marsh model might cause inadvertent propofol underdosing in underweight patients.
      Future studies are necessary to compare the predictive performance of the
      modified Marsh and Schnider pharmacokinetic models in underweight patients.

PMID- 29225744
TI  - A comparison between ketorolac and nefopam as adjuvant analgesics for
      postoperative patient-controlled analgesia: a randomized, double-blind,
      prospective study.
AB  - Background: We compared the analgesic efficacy and side effects of ketorolac and
      nefopam that were co-administered with fentanyl via intravenous patient
      controlled analgesia. Methods: One hundred and sixty patients scheduled for
      laparoscopic cholecystectomy were randomly assigned to ketorolac (Group K) or
      nefopam (Group N) groups. The anesthetic regimen was standardized for all
      patients. The analgesic solution contained fentanyl 600 ug and ketorolac 180 mg
      in Group K, and fentanyl 600 ug and nefopam 120 mg in Group N. The total volume
      of analgesic solution was 120 ml. Postoperative analgesic consumption, recovery
      of pulmonary function, and pain intensities at rest and during the forced
      expiration were evaluated at postoperative 2, 6, 24, and 48 h. The postoperative
      side effects of analgesics were recorded. Results: Cumulative postoperative
      analgesic consumptions at postoperative 48 h were comparable (Group K: 93.4 +/-
      24.0 ml vs. Group N: 92.9 +/- 26.1 ml, P = 0.906) between the groups. Pain scores
      at rest and during deep breathing were similar at the time of each examination.
      The recovery of pulmonary function showed no significant differences between the
      groups. Overall, postoperative nausea and vomiting incidence was higher in Group
      N compared with Group K (59% vs. 34%, P = 0.015). The other side effects were
      comparable between both groups. Conclusions: Analgesic efficacies of ketorolac
      and nefopam that were co-administered with fentanyl for postoperative pain
      management as adjuvant analgesics were similar. However, postoperative nausea and
      vomiting incidence was higher in the nefopam-fentanyl combination compared with
      the ketorolac-fentanyl combination.

PMID- 29225745
TI  - Heated wire humidification circuit attenuates the decrease of core temperature
      during general anesthesia in patients undergoing arthroscopic hip surgery.
AB  - Background: Intraoperative hypothermia is common in patients undergoing general
      anesthesia during arthroscopic hip surgery. In the present study, we assessed the
      effect of heating and humidifying the airway with a heated wire humidification
      circuit (HHC) to attenuate the decrease of core temperature and prevent
      hypothermia in patients undergoing arthroscopic hip surgery under general
      anesthesia. Methods: Fifty-six patients scheduled for arthroscopic hip surgery
      were randomly assigned to either a control group using a breathing circuit
      connected with a heat and moisture exchanger (HME) (n = 28) or an HHC group using
      a heated wire humidification circuit (n = 28). The decrease in core temperature
      was measured from anesthetic induction and every 15 minutes thereafter using an
      esophageal stethoscope. Results: Decrease in core temperature from anesthetic
      induction to 120 minutes after induction was lower in the HHC group (-0.60 +/-
      0.27C) compared to the control group (-0.86 +/- 0.29C) (P = 0.001). However,
      there was no statistically significant difference in the incidence of
      intraoperative hypothermia or the incidence of shivering in the postanesthetic
      care unit. Conclusions: The use of HHC may be considered as a method to attenuate
      intraoperative decrease in core temperature during arthroscopic hip surgery
      performed under general anesthesia and exceeding 2 hours in duration.

PMID- 29225746
TI  - Comparison of the impact of applications of Targeted Transfusion Protocol and
      Massive Transfusion Protocol in trauma patients.
AB  - Background: The current study assessed a recently developed resuscitation
      protocol for bleeding trauma patients called the Targeted Transfusion Protocol
      (TTP) and compared its results with those of the standard Massive Transfusion
      Protocol (MTP). Methods: Per capita utilization of blood products such as packed
      red blood cells (RBCs), fresh frozen plasma (FFP), and platelet concentrates was
      compared along with mortality rates during two 6-month periods, one in 2011 (when
      the standard MTP was followed) and another in 2014 (when the TTP was used). In
      the TTP, patients were categorized into three groups based on the presence of
      head injuries, long bone fractures, or penetrating injuries involving the trunk,
      extremities, or neck who were resuscitated according to separate algorithms. All
      cases had experienced motor vehicle accidents and had injury severity scores over
      16. Results: No statistically significant differences were observed between the
      study groups at hospital admission. Per capita utilization of RBC (4.76 +/- 0.92
      vs. 3.37 +/- 0.55; P = 0.037), FFP (3.71 +/- 1.00 vs. 2.40 +/- 0.52; P = 0.025),
      and platelet concentrate (1.18 +/- 0.30 vs. 0.55 +/- 0.18; P = 0.006) blood
      products were significantly lower in the TTP epoch. Mortality rates were similar
      between the two study periods (P = 0.74). Conclusions: Introduction of the TTP
      reduced the requirements for RBCs, FFP, and platelet concentrates in severely
      injured trauma patients.

PMID- 29225747
TI  - A prospective randomized controlled double-blind trial to assess the effects of
      dexmedetomidine during cleft palate surgery.
AB  - Background: We investigated whether the intraoperative administration of
      dexmedetomidine would attenuate the profound sympathoadrenal response associated
      with cleft palate (CP) surgery. Methods: Sixty children aged 6 months to 12 years
      undergoing CP surgery under general anesthesia were randomly assigned to the
      control (C) or dexmedetomidine (D) groups. Group C received benzodiazepine (0.05
      mg/kg midazolam followed by infusion of normal saline) fentanyl isoflurane
      anesthesia, and Group D received dexmedetomidine (loading 1 ug/kg followed by
      infusion of 0.5 ug/kg/h) fentanyl isoflurane anesthesia. Heart rate (HR), mean
      blood pressure (MBP), intraoperative fentanyl and isoflurane requirements,
      recovery scores, emergence agitation, pain scores, time and requirement of rescue
      analgesic, and surgeon satisfaction were noted. Results: Intraoperative HR and
      MBP in Group D were significantly lower than the corresponding values in Group C
      (P < 0.001). HR decreased up to 16% in Group D. By contrast, HR increased up to
      20% in Group C. Group D had comparable MBP to its baseline, whereas Group C had
      higher MBP until extubation (P = 0.015). Two children in Group D developed
      bradycardia and hypotension, which was successfully treated. The fentanyl and
      isoflurane requirements decreased by 43% and 30%, respectively, in Group D
      patients compared to those in Group C (P < 0.001). Group D had lower pain scores
      and less emergence agitation (P < 0.001). Time until requirement of first rescue
      analgesic was longer in Group D than that in Group C (P < 0.001). Surgeon
      satisfaction was higher in Group D than that in Group C. Conclusions: Intravenous
      dexmedetomidine during CP surgery attenuated hemodynamic responses with excellent
      surgeon satisfaction. Close monitoring of hemodynamics is recommended.

PMID- 29225748
TI  - Multiple exposures of sevoflurane during pregnancy induces memory impairment in
      young female offspring mice.
AB  - Background: Earlier studies have reported conflicting results regarding long-term
      behavioral consequences after anesthesia during the fetal period. Previous
      studies also suggest several factors that may explain such conflicting data.
      Thus, we examined the influence of age and sex on long-term behavioral
      consequences after multiple sevoflurane exposures during the fetal period.
      Methods: C57BL/6J pregnant mice received oxygen with or without sevoflurane for 2
      hours at gestational day (GD) 14-16. Offspring mice were subjected to behavioral
      assays for general activity (open field test), learning, and memory (fear chamber
      test) at postnatal day 30-35. Results: Multiple sevoflurane exposures at GD 14-16
      caused significant changes during the fear chamber test in young female offspring
      mice. Such changes did not occur in young male offspring mice. However, general
      activity was not affected in both male and female mice. Conclusions: Multiple
      sevoflurane exposures in the second trimester of pregnancy affects learning and
      memory only in young female mice. Further studies focusing on diverse cognitive
      functions in an age-, sex-dependent manner may provide valuable insights
      regarding anesthesia-induced neurotoxicity.

PMID- 29225749
TI  - Humble Foley's catheter to the rescue in a case of T-tube insertion: a case
      report.
AB  - The Montgomery T-tube poses a challenge to anesthesiologists because of loss of
      anesthetic gases through the open proximal end of the vertical limb and lack of
      standard anesthesia circuit connectors. Here, we present a case of a 25-year-old
      woman with a reported history of accidental strangulation 18 months previously.
      The patient had a metallic tracheostomy tube in situ due to the development of
      tracheal stenosis. Computed tomography showed significant narrowing in a 7-8-mm
      segment, 2 cm proximal to the tracheostomy tube in situ. She was scheduled for
      tracheal reconstruction surgery and T-tube insertion due to persistent subglottic
      stenosis. In this case, the Foley's catheter, which was inserted into the glottis
      orally, not only aided easy insertion of the T-tube into the trachea through the
      tracheal stoma, but also enabled us to stop the loss of anesthetic gases through
      the proximal vertical limb of the T-tube.

PMID- 29225750
TI  - Opioid-free anesthesia using continuous dexmedetomidine and lidocaine infusions
      in spine surgery.

PMID- 29225751
TI  - Anesthesia for the deaf and mute.

PMID- 29225753
TI  - Study of bacterial flora associated with mobile phones of healthcare workers and
      non-healthcare workers.
AB  - Background and Objectives: Despite improvements in modern diagnosis and
      therapies, hospital acquired infections remain a leading problem of global health
      systems. Healthcare workers mobile phones is a reservoir for potential pathogens.
      Despite the high possibility of being contaminated, mobile phones are rarely
      clean and are often touched during or after examination of patients and handling
      of specimens without proper hand washing. The main objective of the present study
      was to isolate, identify different types of bacteria and their antibiotic
      sensitivity from mobile phones of healthcare workers and non-health-care workers.
      Materials and Methods: Samples were collected aseptically by rolling over the
      exposed surfaces of the mobile phones inoculated on the agar plates and incubated
      aerobically. After incubation, plates were examined for growth. Bacteria were
      identified and antibiotic sensitivity was tested as per standard microbiological
      procedures. Results: In this study a total of 175 samples were examined, out of
      which 125 samples were from healthcare workers (HCWs), 50 samples were from non
      healthcare workers (non-HCWs). Among the mobile phones of HCW's from ICUs,
      Acinetobacter baumannii (36.84%) was the predominant organism isolated followed
      by methicillin resistant Staphylococcus aureus (MRSA) (21.05%). Predominant
      organism isolated from HCW's in operation theater theater was MRSA (46.66%). Out
      of 50 worker's non-HCWs mobile phones samples cultured, 23 (46.00%) samples
      yielded growth of six different types of bacteria. Conclusion: Our study reveals
      that there is definite colonization of bacteria on mobile phones of the HCWs. It
      is not only capable of transferring message but also disease-producing microbes.
      In order to reduce incidence of nosocomial infections, there should be
      implementation of hand washing practices and regulations around the use of mobile
      telephones in hospital settings.

PMID- 29225755
TI  - Evaluation of anti-bacterial effects of nickel nanoparticles on biofilm
      production by Staphylococcus epidermidis.
AB  - Background and Objectives: Staphylococcus epidermidis produces biofilm by
      extracellular polysaccharides, causing bacterial adherence to different surfaces.
      Anti-microbial effects of nickel nanoparticles on some bacterial strains such as
      S. aureus and Escherichia coli have been determined in limited studies. The aim
      of the present study is to examine the inhibitory effect of nickel nanoparticles
      on biofilm formation using clinical isolates of S. epidermidis and its hemolytic
      effect on human red blood cells. Materials and Methods: Twenty two S. epidermidis
      isolates were collected and identified by standard microbiological methods.
      Microtiter plate method was used to determine the biofilm production in bacterial
      isolates. The amounts of biofilm formation by isolates in the presence of 0.01,
      0.05, 0.1, and 1 mg/mL concentrations of nickel nanoparticles were measured.
      Hemolytic activity of different concentrations of nickel nanoparticles was
      measured on human RBC suspensions. Results: Twenty isolates were strong, and two
      isolates were moderate biofilm producers. Biofilm formation significantly
      decreased in the presence of 0.05, 0.1, and 1 mg/mL of nickel nanoparticles
      (p<0.05). Although in the presence of 0.01 mg/mL of nickel nanoparticles,
      decrease in biofilm formation was observed but it was not statistically
      significant (p=0.448). Slight hemolytic activity was seen in the presence of
      nickel nanoparticles. Conclusion: In this study, the ability of biofilm
      production was demonstrated for all clinical isolates of S. epidermidis. On the
      other hand, the lowering effects of nickel nanoparticles on biofilm formation
      were observed.

PMID- 29225754
TI  - Methicillin resistance and selective genetic determinants of Staphylococcus
      aureus isolates with bovine mastitis milk origin.
AB  - Background and Objectives: Staphylococcus aureus is one of the major causes of
      bovine mastitis, which can be transmitted from animals to humans. Methicillin
      resistant S. aureus (MRSA) isolates are more attentive and if not treated
      promptly, they can cause death. The aim of this study was to determine the
      prevalence of methicillin resistance and frequency of selected virulence factors
      of S. aureus isolates with bovine mastitis milk origin in Ahvaz, southwest of
      Iran. Materials and Methods: During a two-year period (2014-2015), 75 S. aureus
      isolates were recovered from referred clinical and sub-clinical bovine mastitis
      milk samples. The isolates were phenotypically investigated for resistance to
      cefoxitin by Kirby-Bauer method. DNA were analyzed by PCR for mecA and selected
      genes that encode the virulence factors. Results: According to the results, the
      spa, ebpS, fnb, bbp, clfA, clfB, and cna genes were detected in 98.7, 97.3, 97.3,
      86.7, 84, 84 and 65.3% of the isolates, respectively. Among the 75 isolates, only
      one (1.3%) isolate was methicillin-resistant. Totally, 39 isolates (50.7%) had
      all of these virulence factors except mecA. The results showed that 96% of the
      isolates had at least the fnb, ebpS and spa genes, signifying the noteworthy role
      of these genes in the pathogenesis of S. aureus bovine intra-mammary infection in
      this area. Conclusion: In the present study, the prevalence of mecA was
      relatively low, possibly indicating that cows do not play a significant role in
      community-acquired MRSA infection in this area. According to the results, studied
      virulence factors were somewhat prevalent, bearing in mind the probable risk of
      transmission of these isolates from cows to humans, especially those that are in
      close contact with infected cattle. The data presented here can be used for the
      introduction of a protective vaccine against this infection.

PMID- 29225756
TI  - Prevalence of Clostridium difficile and its toxigenic genotype in beef samples in
      west of Iran.
AB  - Background and Objectives: Clostridium difficile is the leading cause of
      nosocomial diarrhea and pseudomembranous colitis. The prevalence of C. difficile
      infection differs in various geographical areas. The aim of this study was to
      determine the prevalence of C. difficile isolates and the prevalence of cdd3,
      tcdA and tcdB genes in beef samples in Kermanshah Province. Materials and
      Methods: One hundred ground beef samples were randomly collected from the
      butchers of Kermanshah province during March 2014 to March 2015. Following
      alcohol shock, minced meat samples were incubated in a specific culture medium
      for 5 to 7 days. The suspicious colonies were analyzed by biochemical tests and
      frequency of C. difficile and cdd3, tcdA and tcdB genes was assessed by PCR using
      specific primers. Results: In total, 30% samples were positive for C. difficile
      and all the isolates harbored Cdd3 gene. Combined dual-gene frequency of A+B+, A
      B+ and A+B- strains in the positive were 0%, 3.3%, and 26.6% respectively, while
      21 samples (70%) were non-toxigenic (A-B-). Conclusion: In this study, the
      presence of C. difficile in beef as a source of contamination was confirmed. It
      was also shown that the incidence of C. difficile in ground meat was relatively
      higher than many other studies.

PMID- 29225752
TI  - Emerging and re-emerging infectious diseases in Iran.
AB  - Despite development of preventive and controlling strategies regarding infectious
      diseases, they are still considered as one of the most significant leading causes
      of morbidity and mortality, worldwide. Changes in humans' demographics and
      behaviors, microbial and ecological alterations, agricultural development,
      international travels and susceptibility to infectious diseases have resulted in
      increased reports of emerging infectious diseases (EIDs) and reemerging
      infectious diseases (RIDs) in various geographical areas. Because of the various
      types of geographic properties in Iran, substantial climatic variability, as well
      as unstable political situations and poor public health conditions in some of
      neighboring countries, EIDs and RIDs are serious public health problems; among
      them, zoonotic and drug resistant diseases are the most significant. Hence, this
      review provides an overview of the significant bacterial, viral and fungal EIDs
      and RIDs in Iran regarding their epidemiological aspects.

PMID- 29225757
TI  - Dengue fever in a south Asian metropolis: a report on 219 cases.
AB  - Background and Objectives: Yearly epidemics of Dengue fever occur post-monsoon in
      India's capital, Delhi. A prospective observational study was conducted during
      the outbreak months to understand the epidemiology and outcome of this infection
      and its economic impact. Materials and Methods: Febrile hospitalized (n=219)
      patients with dengue fever diagnosed by a combination of MAC-ELISA, GAC-ELISA and
      NS1Antigen-ELISA were enrolled. Epidemiologic (including economic) parameters,
      clinical, radiological and laboratory manifestations were noted and patients
      followed up over the period of hospital stay. Patient management means and
      outcome were recorded and analysed. Results: As per WHO-2009, 153 (69.9%) and 27
      (12.3%) patients were classified as dengue with warning signs and Severe Dengue
      respectively while according to WHO-1997 guidelines 39 (17.8%) and 18 (8.2%)
      patients were classified as DHF and DSS respectively. 216 patients were from the
      city while three were travellers; hospitalization was more frequent among the
      young and male gender. Fever, vomiting, aches and abdominal pain were the most
      common troublesome manifestations; classical dengue triad was present in 55
      (25.1%) patients; hemorrhagic, neurologic and mucocutaneous manifestations were
      present in 44 (20.1%), 8 (3.7%) and 70 (32%) patients. Ascitis, pleural effusion,
      and Gall bladder wall oedema was found in 53 (24.2%), 31 (14.1%) and 45 (20.5%)
      patients respectively. Mortality was 1.4% (3 deaths); in addition there was an
      intra-uterine fetal death; mean expenditure per patient during the illness was
      US$ 377.25. Conclusion: Dengue virus infection results in immense morbidity and
      substantial mortality.

PMID- 29225758
TI  - An in-vitro transcription assay for development of Rotavirus VP7.
AB  - Background and Objectives: Human rotavirus (RV) is responsible for most cases of
      acute gastroenteritis in infants, worldwide. Today, in vitro transcription (IVT)
      assay is widely used to develop efficient RNA for the biological experiments such
      as gene function analysis and reverse genetics. The aim of this study was to
      develop optimal full-length transcripts of the VP7 segment, using in vitro
      transcription assay. Materials and Methods: Special primers were designed in
      order to synthesize VP7 sequence of sense RNA in the process of IVT using T7 RNA
      polymerase. RT-PCR was performed using forward and reverse primers, containing T7
      promoter sequence and BstUI restriction enzyme site, respectively. In order to
      synthesize ssRNA VP7, in accordance with the IVT technique, RV4-VP7 fragment was
      subcloned into PTZ57 R/T plasmid and digested by BstUI enzyme. Results: The
      sequencing of the VP7 gene showed 99% identity withVP7 gene of rotavirus RV4
      strain (Sequence ID: M64666.1). The analysis of purity of DNA fragment and ssRNA
      VP7 segment revealed that OD ratio of A260/A280 and quantity of nucleic acids
      were (1.9, 0.036 MUg/MUL) and (2.02, 0.98 MUg/MUL), respectively. Conclusion: In
      the present study, a modified methodology of RNA synthetase was described by IVT
      assay, using T7RNA polymerase in order to transcribe the full-length transcripts
      of human VP7-RV4 strain. This method is applicable for reverse genetic
      approaches, especially for the production of reassortant RV vaccine.

PMID- 29225759
TI  - Seroprevalence of hepatitis B, C and D viral among hemodialysis patients in
      Tehran.
AB  - Background and Objectives: Different studies show that the prevalence of
      hepatitis viruses in hemodialysis (HD) patients is much greater than general
      population. It is important to be aware of local prevalence data, in order to
      control infections and prevention of nosocomial transmission. The aim of this
      cross-sectional study was to investigate the seroprevalence of hepatitis B, C,
      and D viral infections among HD patients. Materials and Methods: During 2016, a
      cross-sectional study was conducted in Tehran, among 360 HD patients from 5
      hemodialysis centers. All HBsAg positive subjects were screened for Hepatitis B
      surface Ag (HBsAg), Hepatitis C virus Ab (HCVAb) and Hepatitis D virus antibody
      (HDVAb), using specific enzyme linked immunoassay. Results: 360 patients were
      involved including 213 males (59.17%) and 147 females (40.83%). The mean age in
      current study was 53.43 years. HBV positive (HBsAg positive) was found in 1.39%
      of patients, HCVAb in 3.06%, whereas no HDV positive patient was diagnosed. In
      HD, duration of 1-5 years has the highest frequency rate. Conclusion: Prevalence
      of HBV, HCV and HDV in hemodialysis patients seems low in Tehran province. Due to
      higher prevalence of HCV, it is recommended to check the patients for anti-HCV Ab
      before admission to the centers.

PMID- 29225760
TI  - Irritable bowel syndrome subtype screening characteristics: constipation subtype
      patient profiles explored.
AB  - Irritable bowel syndrome (IBS), a chronic disorder, greatly impacts the lives of
      those affected. Approximately one quarter of the North American population
      suffers from this condition that includes abdominal pain, discomfort and
      alterations in normal bowel function. Constipation-subtype IBS (IBS-C) is often
      found to be a prevalent subtype; however, a lack of knowledge and effective
      treatment options remains surrounding this disorder. In the course of an ongoing
      study conducted by our research team on the use of acupuncture and moxibustion in
      the management of IBS symptoms, a considerable number of screened patients
      havemet the widely accepted Rome III criteria for IBS-C.

PMID- 29225761
TI  - The potential role of hybridization in diversification and speciation in an
      insular plant lineage: insights from synthetic interspecific hybrids.
AB  - Hybridization is recognized as an important process in plant evolution, and this
      may be particularly true for island plants where several biotic and abiotic
      factors facilitate interspecific hybridization. Although rarely done,
      experimental studies could provide insights into the potential of natural
      hybridization to generate diversity when species come into contact in the dynamic
      island setting. The potential of hybridization to generate morphological
      variation was analysed within and among 12 families (inbred lines) of an F4
      hybrid generation between two species of Tolpis endemic to the Canary Islands.
      Combinations of characters not seen in the parents were present in hybrids.
      Several floral and vegetative characters were transgressive relative to their
      parents. Morphometric studies of floral, vegetative and fruit characters revealed
      that several F4 families were phenotypically distinct from other families, and
      from their parents. The study demonstrates that morphologically distinct pollen
      fertile lines, potentially worthy of taxonomic recognition if occurring in
      nature, can be generated in four generations. The ability of the hybrid lines to
      set self-seed would reduce gene flow among the lines, and among the hybrids and
      their parental species. Selfing would also facilitate the fixation of characters
      within each of the lines. Overall, the results show the considerable potential of
      hybridization for generating diversity and distinct phenotypes in island
      lineages.

PMID- 29225763
TI  - Dispersal and establishment of vascular epiphytes in human-modified landscapes.
AB  - The ongoing destruction of old-growth forests puts tropical forest species under
      great pressure because of the resulting habitat loss. A pre-requisite for the
      maintenance of a viable metacommunity in a fragmented landscape is the
      connectivity between habitable patches. We experimentally studied four vital
      steps of epiphyte dispersal in different habitat types in western Panama. (i)
      Seed falling velocity (Vterm) is known to correlate with long-distance dispersal
      via convective updraft. All measured Vterm of bromeliad and orchid seeds fell
      into a range of velocities with a high chance of long-distance dispersal. (ii) We
      quantified attachment success of bromeliad seeds as a function of bark rugosity
      with >30 common tree species in the region. Even fine bark structure allowed
      effective attachment. (iii and iv) Successful establishment is achieved when a
      seed germinates and a plantlet grows and survives. Germination success and early
      establishment of four bromeliad species did not differ between isolated trees,
      teak plantations or secondary forest patches. Microclimatic differences between
      habitat types were marginal and neither germination nor establishment correlated
      significantly with annual precipitation. The findings suggest a large capacity
      for dispersal and successful early establishment for these anemochorous species.
      A potentially regenerating forest may receive considerable input from sources
      such as pasture trees and in this way gain structural complexity, which also
      greatly enhances its value for other forest organisms.

PMID- 29225762
TI  - Functional role of long-lived flowers in preventing pollen limitation in a high
      elevation outcrossing species.
AB  - Low pollinator visitation in harsh environments may lead to pollen limitation
      which can threaten population persistence. Consequently, avoidance of pollen
      limitation is expected in outcrossing species subjected to habitually low
      pollinator service. The elevational decline in visitation rates on many high
      mountains provides an outstanding opportunity for addressing this question.
      According to a recent meta-analysis, levels of pollen limitation in alpine and
      lowland species do not differ. If parallel trends are manifested among
      populations of alpine species with wide elevational ranges, how do their
      uppermost populations contend with lower visitation? We investigated visitation
      rates and pollen limitation in high Andean Rhodolirium montanum. We test the
      hypothesis that lower visitation rates at high elevations are compensated for by
      the possession of long-lived flowers. Visitation rates decreased markedly over
      elevation as temperature decreased. Pollen limitation was absent at the low
      elevation site but did occur at the high elevation site. While initiation of
      stigmatic pollen deposition at high elevations was not delayed, rates of pollen
      arrival were lower, and cessation of pollination, as reflected by realized flower
      longevity, occurred later in the flower lifespan. Comparison of the elevational
      visitation decline and levels of pollen limitation indicates that flower
      longevity partially compensates for the lower visitation rates at high elevation.
      The functional role of flower longevity, however, was strongly masked by
      qualitative pollen limitation arising from higher abortion levels attributable to
      transference of genetically low-quality pollen in large clones. Stronger clonal
      growth at high elevations could counterbalance the negative fitness consequences
      of residual pollen limitation due to low visitation rates and/or difficult
      establishment under colder conditions. Visitation rates on the lower part of the
      elevational range greatly exceeded community rates recorded several decades ago
      when the planet was cooler. Current pollen limitation for some species in some
      habitats might underestimate historical levels.

PMID- 29225764
TI  - Sodium chloride accumulation in glycophyte plants with cyanobacterial symbionts.
AB  - The majority of plant species are glycophytes and are not salt-tolerant and
      maintain low sodium levels within their tissues; if. high tissue sodium
      concentrations do occur, it is in response to elevated environmental salt levels.
      Here we report an apparently novel and taxonomically diverse grouping of plants
      that continuously maintain high tissue sodium contents and share the rare feature
      of possessing symbiotic cyanobacteria. Leaves of Gunnera magellanica in Tierra
      del Fuego always had sodium contents (dry weight basis) of around 4.26 g kg-1,
      about 20 times greater than measured in other higher plants in the community
      (0.29 g kg-1). Potassium and chloride levels were also elevated. This was not a
      response to soil sodium and chloride levels as these were low at all sites. High
      sodium contents were also confirmed in G. magellanica from several other sites in
      Tierra del Fuego, in plants taken to, and cultivated in Madrid for 2 years at low
      soil salt conditions, and also in other free living or cultivated species of
      Gunnera from the UK and New Zealand. Gunnera species are the only angiosperms
      that possess cyanobacterial symbionts so we analysed other plants that have this
      rather rare symbiosis, all being glycophytes. Samples of Azolla, a floating
      aquatic fern, from Europe and New Zealand all had even higher sodium levels than
      Gunnera. Roots of the gymnosperm Cycas revoluta had lower sodium contents (2.52
      +/- 0.34 g kg-1) but still higher than the non-symbiotic glycophytes. The
      overaccumulation of salt even when it is at low levels in the environment appears
      to be linked to the possession of a cyanobacterial symbiosis although the actual
      functional basis is unclear.

PMID- 29225765
TI  - Perspective Space as a Model for Distance and Size Perception.
AB  - In the literature, perspective space has been introduced as a model of visual
      space. Perspective space is grounded on the perspective nature of visual space
      during both binocular and monocular vision. A single parameter, that is, the
      distance of the vanishing point, transforms the geometry of physical space into
      that of perspective space. The perspective-space model predicts perceived angles,
      distances, and sizes. The model is compared with other models for distance and
      size perception. Perspective space predicts that perceived distance and size as a
      function of physical distance are described by hyperbolic functions.
      Alternatively, power functions have been widely used to describe perceived
      distance and size. Comparison of power and hyperbolic functions shows that both
      functions are equivalent within the range of distances that have been judged in
      experiments. Two models describing perceived distance on the ground plane appear
      to be equivalent with the perspective-space model too. The conclusion is that
      perspective space unifies a number of models of distance and size perception.

PMID- 29225766
TI  - On the Discovery of Monocular Rivalry by Tscherning in 1898: Translation and
      Review.
AB  - Monocular rivalry was named by Breese in 1899. He made prolonged observation of
      superimposed orthogonal gratings; they fluctuated in clarity with either one or
      the other grating occasionally being visible alone. A year earlier, Tscherning
      observed similar fluctuations with a grid of vertical and horizontal lines and
      with other stimuli; we draw attention to his prior account. Monocular rivalry has
      since been shown to occur with a wide variety of superimposed patterns with
      several independent rediscoveries of it. We also argue that Helmholtz described
      some phenomenon other than monocular rivalry in 1867.

PMID- 29225767
TI  - Pink Cricket Balls Through Rose-Tinted Glasses: Enhancing Interceptive Timing.
AB  - Cricket is a popular but potentially dangerous sport. It is played with a hard
      ball that can travel at great speeds. Serious injuries, including fatalities,
      have occurred when balls have struck participants. The game is traditionally
      played during daylight with a dark red ball, but recent games have been played
      during the day and at night using a 'pink' ball. We have reported data that
      seemed to justify concerns raised regarding the visibility of these new pink
      balls, as they were revealed to have a very low luminance contrast against
      pertinent backgrounds during twilight. Here, we report on the findings of a
      psychophysical experiment, wherein we mimicked twilight lighting conditions in an
      interceptive timing experiment using a pink moving disc as an analogue for pink
      cricket balls. We show that interceptive timing performance is diminished in
      conditions that mimic twilight. More importantly, we show that wearing glasses
      with a rose-tinted filter can alleviate this adverse impact by enhancing the
      luminance contrast of the pink 'ball' relative to pertinent backgrounds.

PMID- 29225768
TI  - About Face: Matching Unfamiliar Faces Across Rotations of View and Lighting.
AB  - Matching the identities of unfamiliar faces is heavily influenced by variations
      in their images. Changes to viewpoint and lighting direction during face
      perception are commonplace across yaw and pitch axes and can result in dramatic
      image differences. We report two experiments that, for the first time,
      factorially investigate the combined effects of lighting and view angle on
      matching performance for unfamiliar faces. The use of three-dimensional head
      models allowed control of both lighting and viewpoint. We found viewpoint effects
      in the yaw axis with little to no effect of lighting. However, for rotations
      about the pitch axis, there were both viewpoint and lighting effects and these
      interacted where lighting effects were found only for front views and views from
      below. The pattern of effects was similar regardless of whether view variation
      occurred as a result of head (Experiment 1) or camera (Experiment 2) suggesting
      that face matching is not purely image based. Along with face inversion effects
      in Experiment 1, the results of this study suggest that face perception is based
      on shape and surface information and draws on implicit knowledge of upright faces
      and ecological (top) lighting conditions.

PMID- 29225769
TI  - Fabrication of low-cost micropatterned polydimethyl-siloxane scaffolds to
      organise cells in a variety of two-dimensioanl biomimetic arrangements for lab-on
      chip culture platforms.
AB  - We present the rapid-prototyping of type I collagen micropatterns on poly
      dimethylsiloxane substrates for the biomimetic confinement of cells using the
      combination of a surface oxidation treatment and 3-aminopropyl triethoxysilane
      silanisation followed by glutaraldehyde crosslinking. The aim of surface
      treatment is to stabilise microcontact printing transfer of this natural
      extracellular matrix protein that usually wears out easily from poly
      dimethylsiloxane, which is not suitable for biomimetic cell culture platforms and
      lab-on-chip applications. A low-cost CD-DVD laser was used to etch biomimetic
      micropatterns into acrylic sheets that were in turn replicated to poly
      dimethylsiloxane slabs with the desired features. These stamps were finally inked
      with type I collagen for microcontact printing transfer on the culture substrates
      in a simple manner. Human hepatoma cells (HepG2) and rat primary hepatocytes,
      which do not adhere to bare poly-dimethylsiloxane, were successfully seeded and
      showed optimal adhesion and survival on simple protein micropatterns with a
      hepatic cord geometry in order to validate our technique. HepG2 cells also
      proliferated on the stamps. Soft and stiff poly-dimethylsiloxane layers were also
      tested to demonstrate that our cost-effective process is compatible with
      biomimetic organ-on-chip technology integrating tunable stiffness with a
      potential application to drug testing probes development where such cells are
      commonly used.

PMID- 29225770
TI  - Sex determination mode does not affect body or genital development of the central
      bearded dragon (Pogona vitticeps).
AB  - Background: The development of male- or female-specific phenotypes in squamates
      is typically controlled by either temperature-dependent sex determination (TSD)
      or chromosome-based genetic sex determination (GSD). However, while sex
      determination is a major switch in individual phenotypic development, it is
      unknownhow evolutionary transitions between GSD and TSD might impact on the
      evolution of squamate phenotypes, particularly the fast-evolving and diverse
      genitalia. Here, we take the unique opportunity of studying the impact of both
      sex determination mechanisms on the embryological development of the central
      bearded dragon (Pogona vitticeps). This is possible because of the transitional
      sex determination system of this species, in which genetically male individuals
      reverse sex at high incubation temperatures. This can trigger the evolutionary
      transition of GSD to TSD in a single generation, making P. vitticeps an ideal
      model organism for comparing the effects of both sex determination processes in
      the same species. Results: We conducted four incubation experiments on 265 P.
      vitticeps eggs, covering two temperature regimes ("normal" at 28  degrees C and
      "sex reversing" at 36  degrees C) and the two maternal sexual genotypes
      (concordant ZW females or sex-reversed ZZ females). From this, we provide the
      first detailed staging system for the species, with a focus on genital and limb
      development. This was augmented by a new sex chromosome identification
      methodology for P. vitticeps that is non-destructive to the embryo. We found a
      strong correlation between embryo age and embryo stage. Aside from faster growth
      in 36  degrees C treatments, body and external genital development was entirely
      unperturbed by temperature, sex reversal or maternal sexual genotype.
      Unexpectedly, all females developed hemipenes (the genital phenotype of adult
      male P. vitticeps), which regress close to hatching. Conclusions: The tight
      correlation between embryo age and embryo stage allows the precise targeting of
      specific developmental periods in the emerging field of molecular research on P.
      vitticeps. The stability of genital development in all treatments suggests that
      the two sex-determining mechanisms have little impact on genital evolution,
      despite their known role in triggering genital development. Hemipenis retention
      in developing female P. vitticeps, together with frequent occurrences of
      hemipenis-like structures during development in other squamate species, raises
      the possibility of a bias towards hemipenis formation in the ancestral
      developmental programme for squamate genitalia.

PMID- 29225771
TI  - Methylation mediated Gadd45beta enhanced the chemosensitivity of hepatocellular
      carcinoma by inhibiting the stemness of liver cancer cells.
AB  - Background: Defects of the growth arrest DNA damage-inducible gene 45beta
      (Gadd45beta) play an important role in the progression of tumor and confer
      resistance to chemotherapy. However, the role of Gadd45beta in the apoptosis of
      hepatocellular carcinoma is still not clear. Purpose of this study was to explore
      the effect of Gadd45beta on the apoptosis of liver cancer cells, and the possible
      mechanism was examined. Result: In this study, we first confirmed the decreased
      expression of Gadd45beta in human liver cancer tissues and human liver cancer
      cell lines, when compared to the peri-tumor liver tissue and normal liver cells.
      And, it was found that Gadd45beta could inhibit the stemness of liver cancer
      cells, enhancing the apoptosis of cancer cells induced by chemotherapy.
      Furthermore, the results showed that HCC tissues and cell lines showed a higher
      methylation status in Gadd45beta promoter than that in peri-tumor tissues and
      normal liver cells. Methylation was then reversed by pretreatment of SMMC-7721
      and Hep-3B with 5-azacytidine which is the DNA methyltransferase inhibitor. And
      the 5-azacytidine decreased the stemness of SMMC-7721 and Hep-3B, enhanced the
      sensitivity of SMMC-7721 and Hep-3B to cisplatin. Conclusions: Methylation
      mediated Gadd45beta expression inhibited the stemness of liver cancer cells,
      promoting the chemotherapy-induced apoptosis. Thus Gadd45beta may be the
      potential target for enhancing the chemosensitivity of human hepatocellular
      carcinoma.

PMID- 29225772
TI  - Long non-coding RNA GAS5 suppresses pancreatic cancer metastasis through
      modulating miR-32-5p/PTEN axis.
AB  - Background: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5)
      is a well-known tumor suppressor in the pathogenesis of a variety of human
      cancers. The precise role of GAS5 in pancreatic cancer (PC) progression is
      currently unknown, so the aim of this study was to explore the functional
      participation of GAS5 in PC metastasis. Methods: The expression changes of GAS5,
      miR-32-5p and PTEN in human PC specimens and cell lines were compared by means of
      molecular biology methods. Transfection of the recombinant plasmid was applied to
      modulate the expression levels of the target genes. RIP and RNA pull-down assays
      were designed to investigate the interaction between GAS5 and miR-32-5p. The
      effect of GAS5 and miR-32-5p on PC progression was assessed with cell
      proliferation, migration, invasion and apoptosis in vitro. Results: GAS5 and PTEN
      protein were decreased in human PC tissues and cells, but miR-32-5p was
      increased. GAS5 induction greatly inhibited the proliferation, migration and
      invasion of PC cells PANC-1 and BxPC-3 in vitro and simultaneously induced cell
      apoptosis. Moreover, GAS5 positively regulated the expression of PTEN through miR
      32-5p. Furthermore, GAS5 suppressed the proliferation, migration and invasion of
      PC cells through regulating miR-32-5p/PTEN axis. Additionally, this finding was
      further supported by the results of in vivo experiments. Conclusion: GAS5 could
      positively regulate PTEN-induced tumor-suppressor pathway via miR-32-5p, thereby
      suppressing PC metastasis.

PMID- 29225774
TI  - First record of the Ligia baudiniana species complex in the American Gulf of
      Mexico Coastline, as confirmed by morphological and molecular approaches.
AB  - Ligia isopods exhibit a constrained morphology that makes identification
      difficult. In the Greater Caribbean, a convoluted taxonomic history has left the
      distributional limits of Ligia baudiniana unclear. To date, no confirmed records
      of this species exist from the American Gulf of Mexico. Herein, we report the
      presence of L. baudiniana in Sarasota-Manatee Florida, as confirmed by
      morphological and molecular approaches. This is the first record of this species
      in the region and a ~300Km extension of its range. Specimens were collected in
      mangroves, underscoring the importance of protecting these habitats.

PMID- 29225773
TI  - Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from
      childhood to adulthood? A meta-analysis.
AB  - Background: Allergic rhinitis and asthma as single entities affect more boys than
      girls in childhood but more females in adulthood. However, it is unclear if this
      prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma.
      Thus, our aim was to compare sex-specific differences in the prevalence of
      coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood.
      Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex
      specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we
      assessed male-female ratios for coexisting allergic rhinitis and asthma in
      children (0-10 years), adolescents (11-17) and adults (> 17). Electronic searches
      were performed using MEDLINE and EMBASE for the time period 2000-2014. We
      included population-based observational studies, reporting coexisting allergic
      rhinitis and asthma as outcome stratified by sex. We excluded non-original or non
      population-based studies, studies with only male or female participants or
      selective patient collectives. Results: From a total of 6539 citations, 10
      studies with a total of 93,483 participants met the inclusion criteria. The male
      female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65
      (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N =
      2) and 1.03 (0.79; 1.35) in adults (N = 2). Male-female ratios for allergic
      rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2)
      in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. Conclusions:
      The prevalence of coexisting allergic rhinitis and asthma shows a clear male
      predominance in childhood and seems to switch to a female predominance in
      adolescents. This switch was less pronounced for allergic rhinitis only.

PMID- 29225775
TI  - Fibromax-based nonalcoholic fatty liver disease in chronic obstructive pulmonary
      disease patients with obstructive sleep apnea: Methodological considerations.
AB  - The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive
      sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in
      chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur
      Respir J, 2017) attempted to determine the prevalence of liver fibrosis,
      steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom
      had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver
      scores: the FibroTest, SteatoTest and NashTest, from the Fibromax(r) panel. Among
      the main findings, the absence of OSA treatment emerged as independently
      associated with liver fibrosis and steatosis, when compared to effective
      treatment. However, besides the low number of treated patients, no
      polysomnographic respiratory data was provided, making it difficult to
      differentiate the impact of OSA from that of COPD in NAFLD prevalence.
      Furthermore, NAFLD diagnosis relied exclusively on circulating biomarker-based
      liver scores, without histological, imagery or other liver exploratory methods.
      Therefore, in this article, some methodological points are reminded and
      discussed, including the choice of OSA measurements, and the significance of
      ActiTest and AshTest scores from Fibromax(r) in this pathophysiological context.

PMID- 29225777
TI  - Evaluation of electrochemiluminescence immunoassays for immunosuppressive drugs
      on the Roche cobas e411 analyzer.
AB  - Background:  Therapeutic drug monitoring of immunosuppressant drugs are used to
      monitor drug efficacy and toxicity and to prevent organ transplantation
      rejection. This study evaluates the analytical performance of semi-automated
      electrochemiluminescence immunoassays (ECLIA) for cyclosporine (CSA), tacrolimus
      (TAC) and sirolimus (SRL) on the Roche cobas e 411 analyzer at a major transplant
      hospital to identify method suitability and limitations. Methods: Residual whole
      blood samples from patients undergoing immunosuppressant therapy were used for
      evaluation. Experiments included imprecision, linearity, functional sensitivity,
      method comparisons and lot-to-lot assessments. Results: Total imprecision ranged
      from 3.3 to 7.1% for CSA, 3.9 to 9.4% for TAC, and 4.6 to 8.2% for SRL. Linearity
      was verified from 30.0 to 960.9 MUg/L for CSA, from 1.1 to 27.1 MUg/L for TAC,
      and from 0.5 to 32.3 ug/L for SRL. The functional sensitivity met the
      manufacturer's claims and was determined to be <6.5 MUg/L for CSA, 1.1 MUg/L for
      TAC, and <0.1 ug/L for SRL (CV<=20%). Deming regression analysis of method
      comparisons with the ARCHITECT immunoassay yielded slopes of 0.917 (95%CI: 0.885
      0.949) and r of 0.985 for CSA, 0.938 (95%CI: 0.895-0.981) and r of 0.974 for TAC,
      and 0.842 (0.810-1.110) and r of 0.982 for SRL. Deming regression analysis of
      comparisons with the LC-MS/MS method yielded slopes of 1.331 (95%CI: 1.167-1.496)
      and r of 0.969 for CSA, 0.924 (95%CI: 0.843-1.005) and r of 0.984 for TAC, and
      0.971 (95%CI: 0.913-1.030) and r of 0.993 for SRL. Conclusions: The cobas e 411
      ECLIA for CSA, TAC, and SRL have acceptable precision, linearity, and functional
      sensitivity. The method comparisons correlated well with the ARCHITECT
      immunoassay and LC-MS/MS and is fit for therapeutic drug monitoring.

PMID- 29225780
TI  - The decision to delivery interval in emergency caesarean sections: Impact of
      anaesthetic technique and work shift.
AB  - Background: One important task of the emergency anaesthesia service is to provide
      rapid, safe and effective anaesthesia for emergency caesarean sections (ECS). A
      Decision to Delivery Interval (DDI) <30 minutes for ECS is a quality indicator
      for this service. The aim of this study was to assess the DDI and the impact of
      chosen anaesthetic technique (general anaesthesia (GA), spinal anaesthesia (SPA)
      with opioid supplementation, or "top-up" of labour epidural analgesia (tEDA) with
      local anaesthesia and fentanyl mixture) and work shift for ECS at Danderyds
      Hospital, Sweden. Methods: A retrospective chart review of ECS at Danderyds
      Hospital was performed between January and October 2016. Time between decision
      for CS, start of anaesthesia, time for incision and delivery, type of anaesthetic
      technique, and time of day, working hours or on call and day of week, Monday -
      Friday, and weekend was compiled and analysed. Time events are presented as mean
      +/- standard deviation. Non-parametric tests were used. Results: In total, 135
      ECS were analysed: 92% of the cases were delivered within 30 minutes and mean DDI
      for all cases was 17.3+/-8.1 minutes. GA shortened the DDI by 10 and 13 minutes
      compared to SPA and tEDA (p<0.0005). DDI for SPA and tEDA did not differ. There
      was no difference in DDI regarding time of day or weekday. Apgar <7 at 5' was
      more commonly seen in ECS having GA (11 out of 64) compared to SPA (2/30) and
      tEDA (1/41) (p<0.05). Conclusion: GA shortens the DDI for ECS, but the use of SPA
      as well as tEDA with opioid supplementation maintains a short DDI and should be
      considered when time allows. Top-up epidural did not prolong the DDI compared to
      SPA. The day of week or time of ECS had no influence on the anaesthesia service
      as measured by the DDI.

PMID- 29225779
TI  - Risk of solid cancer in patients with mast cell activation syndrome: Results from
      Germany and USA.
AB  - Background:  It has been shown repeatedly that mast cells can promote or prevent
      cancer development and growth. If development and/or progression of a solid
      cancer is substantially influenced by mast cell activity, the frequencies of
      occurrence of solid cancers in patients with primary mast cells disorders would
      be expected to differ from the corresponding prevalence data in the general
      population. In fact, a recent study demonstrated that patients with systemic
      mastocytosis (i.e., a rare neoplastic variant of the primary mast cell activation
      disease) have increased risk for solid cancers, in particular melanoma and non
      melanoma skin cancers. The aim of the present study is to examine whether the
      risk of solid cancer is increased in systemic mast cell activation syndrome
      (MCAS), the common systemic variant of mast cell activation disease. Methods: In
      the present descriptive study, we have analysed a large (n=828) patient group
      with MCAS, consisting of cohorts from Germany and the USA, for occurrence of
      solid forms of cancer and compared the frequencies of the different cancers with
      corresponding prevalence data for German and U.S. general populations. Results:
      Sixty-eight of the 828 MCAS patients (46 female, 22 male) had developed a solid
      tumor before the diagnosis of MCAS was made. Comparison of the frequencies of the
      malignancies in the MCAS patients with their prevalence in the general population
      revealed a significantly increased prevalence for melanoma and cancers of the
      breast, cervix uteri, ovary, lung, and thyroid in MCAS patients. Conclusions: Our
      data support the view that mast cells may promote development of certain
      malignant tumors. These findings indicate a need for increased surveillance of
      certain types of cancer in MCAS patients irrespective of its individual clinical
      presentation.

PMID- 29225778
TI  - Zika virus reservoirs: Implications for transmission, future outbreaks, drug and
      vaccine development.
AB  - Zika virus (ZIKV) was recently declared as a 'Global Health Emergency' by the
      World Health Organization. Various tissue reservoirs of ZIKV in infected humans
      and animals models have been observed, the implications of which are not known.
      Compared to other Flaviviruses, sexual transmission and persistence in the
      genitourinary tract seem to be unique to ZIKV. ZIKV persistence and shedding in
      bodily secretions (e.g. saliva, semen) is a concern for potential disease spread
      and could pose challenges in diagnosis, regulatory guidelines and drug/vaccine
      development. Murine and non-human primate models could be useful to study the
      role of tissue reservoirs in the development of prophylactic or therapeutic
      strategies. There is a need for meta-analysis of the ZIKV infection and virus
      shedding data from infected patients and ZIKV animal models, and additional
      research is needed to fully comprehend the long term implications of tissue
      reservoirs on ZIKV disease pathogenesis and biology.

PMID- 29225776
TI  - The sedentary (r)evolution: Have we lost our metabolic flexibility?
AB  - During the course of evolution, up until the agricultural revolution,
      environmental fluctuations forced the human species to develop a flexible
      metabolism in order to adapt its energy needs to various climate, seasonal and
      vegetation conditions. Metabolic flexibility safeguarded human survival
      independent of food availability. In modern times, humans switched their primal
      lifestyle towards a constant availability of energy-dense, yet often nutrient
      deficient, foods, persistent psycho-emotional stressors and a lack of exercise.
      As a result, humans progressively gain metabolic disorders, such as the metabolic
      syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of
      cancer, cardiovascular disease and Alzheimer's disease, wherever the sedentary
      lifestyle spreads in the world. For more than 2.5 million years, our capability
      to store fat for times of food shortage was an outstanding survival advantage.
      Nowadays, the same survival strategy in a completely altered surrounding is
      responsible for a constant accumulation of body fat. In this article, we argue
      that the metabolic epidemic is largely based on a deficit in metabolic
      flexibility. We hypothesize that the modern energetic inflexibility, typically
      displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating
      suppressed metabolic programs, which became obsolete in an affluent environment,
      particularly the ability to easily switch to ketone body and fat oxidation. In a
      simplified model, the basic metabolic programs of humans' primal hunter-gatherer
      lifestyle are opposed to the current sedentary lifestyle. Those metabolic
      programs, which are chronically neglected in modern surroundings, are identified
      and conclusions for the prevention of chronic metabolic diseases are drawn.

PMID- 29225781
TI  - LSD1, a double-edged sword, confers dynamic chromatin regulation but commonly
      promotes aberrant cell growth.
AB  - Histone-modifying enzymes play a critical role in chromatin remodeling and are
      essential for influencing several genome processes such as gene expression and
      DNA repair, replication, and recombination. The discovery of lysine-specific
      demethylase 1 (LSD1), the first identified histone demethylase, dramatically
      revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in
      a wide range of biological operations, including development, cellular
      differentiation, embryonic pluripotency, and disease (for example, cancer). This
      mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its
      involvement in epigenetic changes throughout development, and its importance in
      physiological and pathological processes.

PMID- 29225783
TI  - A study on the efficacy of APACHE-IV for predicting mortality and length of stay
      in an intensive care unit in Iran.
AB  - Background: Clinical assessment of disease severity is an important part of
      medical practice for prediction of mortality and morbidity in Intensive Care Unit
      (ICU). A disease severity scoring system can be used as guidance for clinicians
      for objective assessment of disease outcomes and estimation of the chance of
      recovery. This study aimed to evaluate the hypothesis that the mortality and
      length of stay in emergency ICUs predicted by APACHE-IV is different to the real
      rates of mortality and length of stay observed in our emergency ICU in Iran.
      Methods: This was a retrospective cohort study conducted on the data of 839
      consecutive patients admitted to the emergency ICU of Nemazi Hospital, Shiraz,
      Iran, during 2012-2015. The relevant variables were used to calculate APACHE-IV. 
      Length of stay and death or discharge, Glasgow coma score, and acute physiology
      score were also evaluated. Moreover, the accuracy of APACHE-IV for mortality was
      assessed using area under the Receiver Operator Characteristic (ROC) curve.
      Results: Of the studied patients, 157 died and 682 were discharged (non-survivors
      and survivors, respectively). The length of stay in the ICU was 10.98+/-14.60,
      10.22 +/- 14.21 and 14.30+/-15.80 days for all patients, survivors, and non
      survivors, respectively. The results showed that APACHE-IV model underestimated
      length of stay in our emergency ICU (p<0.001). In addition, the overall observed
      mortality was 17.8%, while the predicted mortality by APACHE-IV model was 21%.
      Therefore, there was an overestimation of predicted mortality by APACHE-IV model,
      with an absolute difference of 3.2% (p=0.036). Conclusion: The findings showed
      that APACHE-IV was a poor predictor of length of stay and mortality rate in
      emergency ICU. Therefore, specific models based on big sample sizes of Iranian
      patients are required to improve accuracy of predictions.

PMID- 29225782
TI  - Update on GH therapy in adults.
AB  - Over the last three decades, short- and long-term observational studies, clinical
      trials, systematic reviews, and meta-analyses have provided relevant information
      on the efficacy and safety of growth hormone (GH) replacement therapy in adults
      with GH deficiency (AGHD). The knowledge acquired during this time has been
      compiled into different guidelines that offer clinicians an evidence-based,
      practical approach for the management of AGHD. There are, however, still open
      questions in some key areas in which recommendations are supported by only
      moderate or weak evidence. In the last recent years, the development of long
      acting GH preparations has created new therapeutic possibilities by decreasing
      injection frequency, improving adherence and thereby potentially maximizing
      clinical outcomes. The aims of this review are to advance our understanding on
      the diagnosis and treatment of AGHD and to present an update and future
      perspectives on the use of long-acting GH preparations.

PMID- 29225784
TI  - Diagnosing alpha-1 antitrypsin deficiency: the first step in precision medicine.
AB  - Severe alpha-1 antitrypsin (AAT) deficiency is one of the most common serious
      genetic diseases in adults of European descent. Individuals with AAT deficiency
      have a greatly increased risk for emphysema and liver disease. Other
      manifestations include bronchiectasis, necrotizing panniculitis and
      granulomatosis with polyangiitis. Despite the frequency and potential severity,
      AAT deficiency remains under-recognized, and there is often a delay in diagnosis.
      This review will focus on three recent updates that should serve to encourage
      testing and diagnosis of AAT deficiency: first, the publication of a randomized
      clinical trial demonstrating the efficacy of intravenous augmentation therapy in
      slowing the progression of emphysema in AAT deficiency; second, the mounting
      evidence showing an increased risk of lung disease in heterozygous PI MZ genotype
      carriers; last, the recent publication of a clinical practice guideline,
      outlining diagnosis and management. Though it has been recognized for more than
      fifty years, AAT deficiency exemplifies the modern paradigm of precision
      medicine, with a diagnostic test that identifies a genetic subtype of a
      heterogeneous disease, leading to a targeted treatment.

PMID- 29225785
TI  - Golgi structure formation, function, and post-translational modifications in
      mammalian cells.
AB  - The Golgi apparatus is a central membrane organelle for trafficking and post
      translational modifications of proteins and lipids in cells. In mammalian cells,
      it is organized in the form of stacks of tightly aligned flattened cisternae, and
      dozens of stacks are often linked laterally into a ribbon-like structure located
      in the perinuclear region of the cell. Proper Golgi functionality requires an
      intact architecture, yet Golgi structure is dynamically regulated during the cell
      cycle and under disease conditions. In this review, we summarize our current
      understanding of the relationship between Golgi structure formation, function,
      and regulation, with focus on how post-translational modifications including
      phosphorylation and ubiquitination regulate Golgi structure and on how Golgi
      unstacking affects its functions, in particular, protein trafficking,
      glycosylation, and sorting in mammalian cells.

PMID- 29225787
TI  - Creutzfeldt-Jakob disease: recent developments.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare prion disorder that has been the
      subject of both professional and public interest following the identification of
      variant CJD as a zoonotic disorder. There have been recent advances in diagnostic
      techniques, including real-time quaking-induced conversion and magnetic resonance
      imaging brain scan, that have allowed more accurate case recognition in all forms
      of CJD. Although the epidemic of variant CJD is clearly in decline, prevalence
      studies suggest that it may be premature to be complacent about concerns for
      public health.

PMID- 29225786
TI  - Recent advances in managing idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a rare pulmonary disease with a poor
      prognosis and severe impact on quality of life. Early diagnosis is still
      challenging and important delays are registered before final diagnosis can be
      reached. Available tools fail to predict the variable course of the disease and
      to evaluate response to antifibrotic drugs. Despite the recent approval of
      pirfenidone and nintedanib, significant challenges remain to improve prognosis
      and quality of life. It is hoped that the new insights gained in pathobiology in
      the last few years will lead to further advances in the diagnosis and management
      of IPF. Currently, early diagnosis and prompt initiation of treatments reducing
      lung function loss offer the best hope for improved outcomes. This article aims
      at providing an overview of recent advances in managing patients with IPF and has
      a particular focus on how to reach a diagnosis, manage comorbidities and lung
      transplantation, care for the non-pharmacological needs of patients, and address
      palliative care.

PMID- 29225788
TI  - Whole-exome sequencing for detecting inborn errors of immunity: overview and
      perspectives.
AB  - The study of inborn errors of immunity is based on a comprehensive clinical
      description of the patient's phenotype and the elucidation of the underlying
      molecular mechanisms and their genetic etiology. Deciphering the pathogenesis is
      key to genetic counseling and the development of targeted therapy. This review
      shows the power of whole-exome sequencing in detecting inborn errors of immunity
      along five central steps taken in whole-exome sequencing analysis. In parallel,
      we highlight the challenges for the clinical and scientific use of the method and
      how these hurdles are currently being addressed. We end by ruminating on major
      areas in the field open to future research.

PMID- 29225789
TI  - Taking control: reorganization of the host cytoskeleton by Chlamydia.
AB  - Both actin and microtubules are major cytoskeletal elements in eukaryotic cells
      that participate in many cellular processes, including cell division and
      motility, vesicle and organelle movement, and the maintenance of cell shape.
      Inside its host cell, the human pathogen Chlamydia trachomatis manipulates the
      cytoskeleton to promote its survival and enhance its pathogenicity. In
      particular, Chlamydia induces the drastic rearrangement of both actin and
      microtubules, which is vital for its entry, inclusion structure and development,
      and host cell exit. As significant progress in Chlamydia genetics has greatly
      enhanced our understanding of how this pathogen co-opts the host cytoskeleton, we
      will discuss the machinery used by Chlamydia to coordinate the reorganization of
      actin and microtubules.

PMID- 29225790
TI  - Update on ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is the most frequent life-threatening
      nosocomial infection in intensive care units. The diagnostic is difficult because
      radiological and clinical signs are inaccurate and could be associated with
      various respiratory diseases. The concept of infection-related ventilator
      associated complication has been proposed as a surrogate of VAP to be used as a
      benchmark indicator of quality of care. Indeed, bundles of prevention measures
      are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory
      secretions must be collected for bacteriological secretions before any new
      antimicrobials. Quantitative distal bacteriological exams may be preferable for a
      more reliable diagnosis and therefore a more appropriate use antimicrobials. To
      improve the prognosis, the treatment should be adequate as soon as possible but
      should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic
      selection pressure. For empiric treatments, the selection of antimicrobials
      should consider the local prevalence of microorganisms along with their
      associated susceptibility profiles. Critically ill patients require high dosages
      of antimicrobials and more specifically continuous or prolonged infusions for
      beta-lactams. After patient stabilization, antimicrobials should be maintained
      for 7-8 days. The evaluation of VAP treatment based on 28-day mortality is being
      challenged by regulatory agencies, which are working on alternative surrogate
      endpoints and on trial design optimization.

PMID- 29225791
TI  - Recent advances in the management and understanding of diabetic retinopathy.
AB  - Despite recent advances in the diagnosis and treatment of diabetic retinopathy,
      this complication remains a steadfast challenge to patients and physicians. This
      review summarizes recent progress in the diagnosis and management of diabetic
      retinopathy, including automated screening, optical coherence tomography, control
      of systemic risk factors, surgical techniques, laser treatment, and
      pharmaceutical treatment, including vascular endothelial growth factor
      inhibitors. Recent advances in pharmaceutical treatments, in particular, hold
      strong promise of halting and sometimes reversing the disease process. Clinicians
      nevertheless must remain vigilant in their efforts to diagnose and treat this
      disease early in its course.

PMID- 29225792
TI  - Epigenetic and transcriptional control of mast cell responses.
AB  - Mast cells are tissue-resident, innate immune cells present in most tissues of
      the body and are important effector and immunomodulatory cells. Differentiated
      mast cells typically are characterized by the surface expression of the receptors
      KIT and FcepsilonRI, the latter especially being important for stimulation
      through IgE antibodies, although these cells have the ability to respond to a
      wide variety of environmental signals, to which they can variably react by
      releasing pre-stored or de novo-synthesized mediators or both. Since mast cells
      terminate their differentiation in their tissue of residence in response to
      specific microenvironmental cues, each tissue may comprise unique mast cell
      subtypes, and responses are tailored to the danger signals that are likely to be
      encountered in each anatomical location. From a transcriptional point of view,
      these cells therefore must be endowed with epigenetic and transcriptional
      programs that allow them to maintain a stable identity and at the same time allow
      sufficient plasticity to adapt to different environmental challenges. In this
      commentary, we highlight some of the recent findings that advanced our
      understanding of the transcriptional and epigenetic programs regulating mast cell
      functions.

PMID- 29225793
TI  - Recent advances in acute pain management: understanding the mechanisms of acute
      pain, the prescription of opioids, and the role of multimodal pain therapy.
AB  - In this review, we discuss advances in acute pain management, including the
      recent report of the joint American Pain Society and American Academy of Pain
      Medicine task force on the classification of acute pain, the role of psychosocial
      factors, multimodal pain management, new non-opioid therapy, and the effect of
      the "opioid epidemic". In this regard, we propose that a fundamental principle in
      acute pain management is identifying patients who are most at risk and providing
      an "opioid free anesthesia and postoperative analgesia". This can be achieved by
      using a multimodal approach that includes regional anesthesia and minimizing the
      dose and the duration of opioid prescription. This allows prescribing medications
      that work through different mechanisms. We shall also look at the recent
      pharmacologic and treatment advances made in acute pain and regional anesthesia.

PMID- 29225796
TI  - Synthesis of Uniform Rare Earth Doped Gd2O2S Sub-micron Sized Spheres Using Gas
      Aided Sulfurization and their Optical Characteristics.
AB  - In this work, we report a detailed study of the synthesis of sub-micron sized
      Gd2O2S spheres using a two-step process: (1) amorphous precursor synthesis using
      the solvothermal method where a surfactant was used to control particle
      morphology, followed by (2) crystallization to form Gd2O2S polycrystalline
      spheres in a sulfur-rich environment. The crystallization and sulfurization
      processes are investigated by monitoring the crystal growth at different
      temperatures and under different environments using mainly x-ray diffraction and
      analysis of the precursor's thermal decomposition profile. The optical emissions
      of the Er and Yb-Er doped Gd2O2S upon excitation at 975 nm were investigated to
      identify the optimal dopant concentrations, optimal heat treatment temperature as
      well as to further elucidate any fine structure changes. Our results also show
      that the maximum emission intensities were obtained for a heat treatment
      temperature of 800  degrees C, where increased dopant diffusion coupled with non
      uniform surface segregation at much higher temperatures led to non-uniform dopant
      distribution and reduced emission intensities. Our findings from these studies
      would be useful towards the synthesis of brightly-emitting Gd2O2S based
      luminescent materials as well as for the controlled gas-aided sulfurization of
      other metal oxysulfides.

PMID- 29225794
TI  - Premature Ovarian Insufficiency - an update on recent advances in understanding
      and management.
AB  - Premature ovarian insufficiency is a complex and relatively poorly understood
      entity with a myriad of etiologies and multisystem sequelae that stem from
      premature deprivation of ovarian sex hormones. Timely diagnosis with a clear
      understanding of the various comorbidities that can arise from estrogen
      deficiency is vital to appropriately counsel and treat these patients. Prompt
      initiation of hormone therapy is critical to control the unsolicited menopausal
      symptoms that many women experience and to prevent long-term health
      complications. Despite ongoing efforts at improving our understanding of the
      mechanisms involved, any advancement in the field in recent decades has been
      modest at best and researchers remain thwarted by the complexity and
      heterogeneity of the underpinnings of this entity. In contrast, the practice of
      clinical medicine has made meaningful strides in providing assurance to the women
      with premature ovarian insufficiency that their quality of life as well as long
      term health can be optimized through timely intervention. Ongoing research is
      clearly needed to allow pre-emptive identification of the at-risk population and
      to identify mechanisms that if addressed in a timely manner, can prolong ovarian
      function and physiology.

PMID- 29225795
TI  - Multiple system atrophy: genetic risks and alpha-synuclein mutations.
AB  - Multiple system atrophy (MSA) is one of the few neurodegenerative disorders where
      we have a significant understanding of the clinical and pathological
      manifestations but where the aetiology remains almost completely unknown.
      Research to overcome this hurdle is gaining momentum through international
      research collaboration and a series of genetic and molecular discoveries in the
      last few years, which have advanced our knowledge of this rare synucleinopathy.
      In MSA, the discovery of alpha-synuclein pathology and glial cytoplasmic
      inclusions remain the most significant findings. Families with certain types of
      alpha-synuclein mutations develop diseases that mimic MSA, and the spectrum of
      clinical and pathological features in these families suggests a spectrum of
      severity, from late-onset Parkinson's disease to MSA. Nonetheless, controversies
      persist, such as the role of common alpha-synuclein variants in MSA and whether
      this disorder shares a common mechanism of spreading pathology with other protein
      misfolding neurodegenerative diseases. Here, we review these issues, specifically
      focusing on alpha-synuclein mutations.

PMID- 29225797
TI  - Seasonal clustering of sinopulmonary mucormycosis in patients with hematologic
      malignancies at a large comprehensive cancer center.
AB  - Background: Invasive Mucorales infections (IMI) lead to significant morbidity and
      mortality in immunocompromised hosts. The role of season and climatic conditions
      in case clustering of IMI remain poorly understood. Methods: Following detection
      of a cluster of sinopulmonary IMIs in patients with hematologic malignancies, we
      reviewed center-based medical records of all patients with IMIs and other
      invasive fungal infections (IFIs) between January of 2012 and August of 2015 to
      assess for case clustering in relation to seasonality. Results: A cluster of 7
      patients were identified with sinopulmonary IMIs (Rhizopus
      microsporus/azygosporus, 6; Rhizomucor pusillus, 1) during a 3 month period
      between June and August of 2014. All patients died or were discharged to hospice.
      The cluster was managed with institution of standardized posaconazole prophylaxis
      to high-risk patients and patient use of N-95 masks when outside of protected
      areas on the inpatient service. Review of an earlier study period identified 11
      patients with IMIs of varying species over the preceding 29 months without
      evidence of clustering. There were 9 total IMIs in the later study period (12
      month post-initial cluster) with 5 additional cases in the summer months, again
      suggesting seasonal clustering. Extensive environmental sampling did not reveal a
      source of mold. Using local climatological data abstracted from National Centers
      for Environmental Information the clusters appeared to be associated with high
      temperatures and low precipitation. Conclusions: Sinopulmonary Mucorales clusters
      at our center had a seasonal variation which appeared to be related to
      temperature and precipitation. Given the significant mortality associated with
      IMIs, local climatic conditions may need to be considered when considering center
      specific fungal prevention and prophylaxis strategies for high-risk patients.

PMID- 29225798
TI  - 30-day readmission, antibiotics costs and costs of delay to adequate treatment of
      Enterobacteriaceae UTI, pneumonia, and sepsis: a retrospective cohort study.
AB  - Background: Enterobacteriaceae are common pathogens in pneumonia, sepsis and
      urinary tract infection (UTI). Though rare, carbapenem resistance (CRE) among
      these organisms complicates efforts to ensure adequate empiric antimicrobial
      therapy. In turn this negatively impacts such outcomes as mortality and hospital
      costs. We explored proportion of total costs represented by antibiotics, 30-day
      readmission rates, and per-day costs of inadequate antimicrobial coverage among
      patients with Enterobacteriaceae pneumonia, sepsis and/or UTI in the context of
      inappropriate (IET) vs. appropriate empiric (non-IET) therapy and carbapenem
      resistance (CRE) vs. susceptibility (CSE). Methods: We conducted a retrospective
      cohort study in the Premier Research database (2009-2013) of 175 US hospitals. We
      included all adult patients admitted with a culture-confirmed UTI, pneumonia, or
      sepsis as principal diagnosis, or as a secondary diagnosis in the setting of
      respiratory failure. Patients with hospital acquired infections or transfers from
      other acute facilities were excluded. IET was defined as failure to administer an
      antibiotic therapy in vitro active against the culture-confirmed pathogen within
      2 days of admission. Results: Among 40,137 patients with Enterobacteriaceae
      infections (54.2% UTI), 4984 (13.2%) received IET. CRE (3.1%) was more frequent
      in patients given IET (13.0%) than non-IET (1.6%, p < 0.001). The proportions of
      total costs represented by antibiotics were similar in IET and non-IET (3.3% vs.
      3.4%, p = 0.01), and higher among the group with CRE than CSE (4.2% vs. 3.4%, p <
      0.001). The 30-day readmission rates were higher in both IET than non-IET (25.6%
      vs. 21.1%, p < 0.001) and CRE than CSE (29.7% vs. 21.5%, p < 0.001) groups. Each
      additional day of inadequate therapy cost an additional $766 (95% CI $661, $870,
      p < 0.001) relative to adequate treatment. Conclusions: In this large US cohort
      of Enterobacteriaceae infections, the cost of antibiotics was a small component
      of total costs, irrespective of whether empiric treatment was appropriate or
      whether a CRE was isolated. In contrast, each extra day of inadequate treatment
      added >$750 to hospital costs. Both CRE and IET were associated with an increased
      risk of readmission within 30 days.

PMID- 29225799
TI  - Kidney involvement in the Schnitzler syndrome, a rare disease.
AB  - The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates
      a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs
      and symptoms of systemic inflammation. During the past 45 years, the SS has
      evolved from an elusive little-known disorder to the paradigm of a late-onset
      acquired auto-inflammatory syndrome. Though there is no definite proof of its
      precise pathogenesis, it should be considered as an acquired disease involving
      abnormal stimulation of the innate immune system, which can be reversed by the
      interleukin-1 receptor antagonist anakinra. It clearly expands our view of this
      group of rare genetic diseases and makes the concept of auto-inflammation
      relevant in polygenic acquired diseases as well. Increasing numbers of
      dermatologists, rheumatologists, allergologists, haematologists and, more
      recently, nephrologists, recognize the SS. The aim of this review is to focus on
      kidney involvement in the SS. Although the literature regarding kidney
      involvement in the SS is very poor it can be severe, as in our own case here
      reported, leading us to recommend the systematic search for nephropathy markers
      in the SS.

PMID- 29225800
TI  - Recommendations for imaging-based diagnosis and management of renal
      angiomyolipoma associated with tuberous sclerosis complex.
AB  - Renal angiomyolipomas are found in up to 80% of tuberous sclerosis complex (TSC)
      patients. Although these tumours are usually asymptomatic, lesions >3 cm in
      diameter are prone to bleeding and up to 10% of TSC patients may experience a
      massive and potentially fatal retroperitoneal haemorrhage. Diagnosis can be
      complicated because of the initial lack of symptoms and the fat-poor content of
      atypical renal angiomyolipomas. After diagnosis, tumour growth and the emergence
      of new tumours must be monitored. Treatment with mammalian target of rapamycin
      (mTOR) inhibitors can reduce tumour size and is indicated in patients with TSC
      associated renal angiomyolipomas >3 cm in diameter. Imaging-based assessment of
      kidney disease is essential to the diagnosis and management of patients with TSC.
      The aims of imaging studies in this context are to detect and characterize
      tumours, assess and detect the risk of complications and evaluate the response to
      treatment, especially in patients treated with mTOR inhibitors. A
      multidisciplinary expert panel developed a series of recommendations based on
      current evidence and professional experience for imaging studies in adults and
      children with TSC-associated renal angiomyolipoma. The recommendations cover
      radiological diagnosis and follow-up of the classic and atypical or fat-poor TSC
      associated renal angiomyolipomas, biopsy indications, minimal requirements for
      radiological requests and reports and recommended technical features and
      protocols for computed tomography and magnetic resonance imaging.

PMID- 29225801
TI  - Histologic regression of fibrillary glomerulonephritis: the first report of
      biopsy-proven spontaneous resolution of disease.
AB  - Fibrillary glomerulonephritis (FGN) is a rare immune complex type
      glomerulonephritis characterized by glomerular deposition of randomly oriented
      fibrils measuring 10-30 nm in thickness, and typically presents with proteinuria
      with or without renal insufficiency and hematuria. We present a case in which a
      patient initially presented at age 41 years with nephrotic-range proteinuria and
      hypertension; a kidney biopsy showed FGN. The patient was treated with
      angiotensin receptor blockage only, without immunosuppression as per patient
      preference, and the level of protein in the urine improved. During the follow-up
      period of 17 years, the patient developed type 2 diabetes mellitus. The patient
      re-presented with nephrotic-range proteinuria 17 years later, at the age of 58
      years. A kidney biopsy was performed and showed diffuse diabetic
      glomerulosclerosis with secondary focal segmental glomerulosclerosis and related
      vascular changes. There was no evidence of FGN by immunofluorescence or electron
      microscopy. Although FGN has been rarely reported to regress clinically, this is
      the first documented case of histologic regression of FGN. The potential for FGN
      fibrils to regress spontaneously is important in the management of FGN patients
      considering that currently available immunosuppressive agents have limited
      efficacy, and is an encouraging finding for future studies aiming to find a cure
      for the disease.

PMID- 29225802
TI  - Effective immunosuppressive management with belatacept and eculizumab in post
      transplant aHUS due to a homozygous deletion of CFHR1/CFHR3 and the presence of
      CFH antibodies.
AB  - Atypical haemolytic uraemic syndrome (aHUS) may clinically present as acute renal
      graft failure resulting from excessive activation of the complement cascade.
      While mutations of complement-encoding genes predispose for aHUS, it is generally
      thought to require an additional insult (e.g. drugs) to trigger and manifest the
      full-blown clinical syndrome. Calcineurin inhibitors (CNIs) used for
      immunosuppression act as potential triggers, especially in the post
      transplantation setting. Therefore, CNI-free immunosuppressive regimens may be
      beneficial. We report on a 58-year-old woman who developed aHUS with acute graft
      failure within 20 days after renal transplantation. Genetic investigation
      revealed a homozygous deletion of the CFH-related 1 (CFHR1) and CFHR3 genes in
      addition to the presence of autoantibodies against complement factor H (CFH). The
      patient was treated with plasmapheresis and administration of the complement
      component 5 (C5) antibody eculizumab, and her immunosuppressive regimen was
      switched from CNI (tacrolimus) to the cytotoxic T-lymphocyte-associated protein 4
      (CTLA-4) inhibitor belatacept. Renal graft function recovered and stabilized over
      an 18-month follow-up period. We describe the successful management of post
      transplant aHUS using a CNI-free immunosuppressive regimen based on eculizumab
      and belatacept. Ideally, adequate molecular diagnostics, performed prior to
      transplantation, can identify relevant genetic risk factors for graft failure and
      help to select patients for individualized immunosuppressive regimens.

PMID- 29225805
TI  - Hospital procedure volume does not predict acute kidney injury after coronary
      artery bypass grafting-a nationwide study.
AB  - Background: Acute kidney injury (AKI) is common after coronary artery bypass
      grafting (CABG) and is associated with poor outcome. Increased hospital procedure
      volume has been associated with better outcomes. However, the impact of hospital
      CABG volume on AKI needing dialysis (AKI-D) is less clear. We designed this study
      to examine (i) the impact of number of annual CABG procedures per hospital (CABG
      vol) on AKI-D and inpatient mortality and (ii) if it modifies the relationship
      between AKI-D and mortality. Methods: Using the Nationwide Inpatient Sample
      database from 2000 to 2010, we identified admissions with CABG and those with AKI
      D using International Classification of Diseases, Ninth Revision, Clinical
      Modification codes. Multivariable logistic regressions were used to assess the
      impact of CABG-vol on AKI-D and mortality. We used restricted cubic splines to
      account for the nonlinear relationship between CABG-vol and mortality. We also
      evaluated the a priori interaction term between CABG-vol and AKI-D in the model
      for mortality. Results: Of 4 002 730 hospitalizations for CABG, 0.7% (24 126) had
      AKI-D. On adjusted analysis, CABG-vol did not correlate with odds of developing
      AKI-D [odds ratio (OR) 0.99; 95% confidence interval (CI) 0.99-1.00] but was
      associated with mortality, though the association was nonlinear. AKI-D was a
      significant predictor of mortality with OR 7.58 (95% CI 6.81-8.44). The
      interaction of CABG-vol and AKI-D was not significant (P = 0.8). Conclusions:
      Lower annual CABG hospital procedure volume is significantly associated with
      higher mortality but not with a higher incidence of AKI-D. AKI-D is associated
      with higher mortality in those undergoing CABG. However, there is no differential
      effect of hospital volume on odds of mortality due to AKI-D.

PMID- 29225806
TI  - Renal artery intervention utilizing carbon dioxide angiography.
AB  - Carbon dioxide angiography is an established non-nephrotoxic option for imaging
      of the infradiaphragmatic arteries and veins. Safe performance of the technique
      once required a somewhat cumbersome system, however, recent innovations have
      simplified implementation and expanded the user base for this technique. As such,
      patient access has also increased. In this issue, Hameed et al. provide initial
      feasibility data regarding carbon dioxide angiography and renal denervation
      therapy. This experience may be translated into future renovascular interventions
      in patients with limited renal reserve.

PMID- 29225803
TI  - Environmental toxin-induced acute kidney injury.
AB  - Human beings are exposed to various potentially toxic agents and conditions in
      their natural and occupational environments. The kidney, due to its concentrating
      ability and excretory function, is highly vulnerable to the effects of
      environmental toxins. Identifying the precise cause and mechanisms of
      environmentally induced renal injury remains a challenge for which various
      scientific disciplines need to be involved. Investigations in this field are
      confronted with the apparent infinite types of toxins, their mutual interaction,
      handling/metabolization by the body, ways of exposure, etc. Although
      interdisciplinary efforts and persistence are required to identify,
      mechanistically unravel and tackle environmental toxin-induced pathologies,
      research eventually pays off in ameliorated working/living conditions and
      development of preventive/therapeutic strategies. This review was compiled to
      particularly emphasize the need for a maintained awareness of environmental
      threats in general and those targeting the kidney. Different mechanisms of renal
      toxicity are illustrated and discussed, thereby focusing on three types of
      environmental toxins, namely aristolochic acid, melamine and heavy metals.

PMID- 29225804
TI  - Angiotensinogen as a biomarker of acute kidney injury.
AB  - Early recognition of acute kidney injury (AKI) is critical to prevent its
      associated complications as well as its progression to long term adverse outcomes
      like chronic kidney disease. A growing body of evidence from both laboratory and
      clinical studies suggests that inflammation is a key factor contributing to the
      progression of AKI regardless of the initiating event. Biomarkers of inflammation
      are therefore of interest in the evaluation of AKI pathogenesis and prognosis.
      There is evidence that the renin angiotensin aldosterone system is activated in
      AKI, which leads to an increase in angiotensin II (Ang II) formation within the
      kidney. Ang II activates pro-inflammatory and pro-fibrotic pathways that likely
      contribute to the progression of AKI. Angiotensinogen is the parent polypeptide
      from which angiotensin peptides are formed and its stability in urine makes it a
      more convenient marker of renin angiotensin system activity than direct
      measurement of Ang II in urine specimens, which would provide more direct
      information. The potential utility of urinary angiotensinogen as a biomarker of
      AKI is discussed in light of emerging data showing a strong predictive value of
      AKI progression, particularly in the setting of decompensated heart failure. The
      prognostic significance of urinary angiotensinogen as an AKI biomarker strongly
      suggests a role for renin-angiotensin system activation in modulating the
      severity of AKI and its outcomes.

PMID- 29225807
TI  - Renal denervation using carbon dioxide renal angiography in patients with
      uncontrolled hypertension and moderate to severe chronic kidney disease.
AB  - Background: Chronic kidney disease (CKD) is the most common cause of secondary
      hypertension. More than half of the patients have uncontrolled hypertension
      (>=140/90 mmHg on three or more antihypertensive agents at optimum doses). Renal
      sympathetic denervation (RSDN) has been shown to reduce blood pressure (BP) in
      patients with resistant hypertension. Although patients with CKD have high
      sympathetic drive, all major clinical trials have excluded patients with
      estimated glomerular filtration rates (eGFRs) <45 mL/min/1.73m2 for risk of
      contrast-induced nephropathy. Methods: In this pilot study, carbon dioxide (CO2)
      was used as the sole contrast agent to carry out renal angiography and RSDN in
      patients with moderate to severe CKD (eGFR 15-44 mL/min/1.73m2) and uncontrolled
      hypertension. Results: Eleven patients (eight males) underwent RSDN. The median
      age was 57 years [interquartile range (IQR) 49-66]. The median number of
      antihypertensives being taken at baseline was 4 (IQR 3-4). No statistically
      significant difference was observed in serum creatinine in the serial follow-ups
      until at 6 months[median difference 0.25 mg/dL (IQR 0.09-0.53); P = 0.008]. There
      was a non-significant reduction in median clinic BP from baseline to 6 months [
      14 mmHg (IQR -24-5)] and a significant increase in daytime ambulatory systolic BP
      [7 mmHg (IQR -2-12); P= 0.045]. A trend towards a serial reduction in albuminuria
      was observed. Procedure-related complications included a groin haematoma (n = 1)
      and reported flank (n = 1) and groin pain (n = 1). Conclusions: This pilot study
      shows that CO2 renal angiography can be used to perform RSDN in patients with
      significant renal impairment and may lead to associated improvements in clinic BP
      and albuminuria.

PMID- 29225808
TI  - Symptom burden in patients with chronic kidney disease not requiring renal
      replacement therapy.
AB  - Background: Although evidence shows that patients with end stage renal disease
      (ESRD) experience a high symptom burden which impacts on quality of life (QoL),
      less is known about patients with earlier stages of chronic kidney disease (CKD).
      This study aimed to explore symptom burden and potential contributing factors in
      patients with CKD Stage 1-5 not requiring renal replacement therapy (RRT).
      Methods: Patients with CKD Stage 1-5 and not on RRT were asked to report their
      symptoms using the Leicester Uraemic Symptom Score (LUSS), a questionnaire which
      assesses the frequency and intrusiveness of 11 symptoms commonly reported by
      kidney patients. Results: Symptoms were assessed in 283 CKD Stage 1-5 patients:
      54% male, mean age 60.5 standard error+/- 1.0, mean eGFR 38ml/min/1.73m2. Some
      96% (95% confidence interval 93.2-98.0) of participants reported experiencing at
      least one symptom, the median reported being six. Excessive tiredness (81%;76.0
      85.6), sleep disturbance (70%;64.3-75.3) and pain in bones/joints (69%;63.4-74.6)
      were reported most commonly. Overall, few significant associations were found
      between biochemical markers of disease severity and symptom burden. Men tended to
      report fewer symptoms than women and South Asian patients often described
      experiencing symptoms with a greater severity. Older patients found
      musculoskeletal symptoms more intrusive whereas younger patients found reduced
      concentration more intrusive. Conclusions: Our findings suggest that patients
      with CKD stages 1-5 experience a multitude of symptoms that could potentially
      impact QoL. Using multidimensional tools like the LUSS, more exploration and
      focus could provide a greater opportunity for patient focussed symptom control
      from the earliest stages of CKD.

PMID- 29225809
TI  - Venous air embolism related to the use of central catheters revisited: with
      emphasis on dialysis catheters.
AB  - Venous air embolism is a dreaded condition particularly relevant to the field of
      nephrology. In the face of a favourable, air-to-blood pressure gradient and an
      abnormal communication between the atmosphere and the veins, air entrance into
      the circulation is common and can bring about venous air embolism. These air
      emboli can migrate to different areas through three major routes: pulmonary
      circulation, paradoxical embolism and retrograde ascension to the cerebral venous
      system. The frequent undesirable outcome of this disease entity, despite timely
      and aggressive treatment, signifies the importance of understanding the
      underlying pathophysiological mechanism and of the implementation of various
      preventive measures. The not-that-uncommon occurrence of venous air embolism,
      often precipitated by improper patient positioning during cervical catheter
      procedures, suggests that awareness of this procedure-related complication among
      health care workers is not universal. This review aims to update the
      pathophysiology of venous air embolism and to emphasize the importance of
      observing the necessary precautionary measures during central catheter use in
      hopes of eliminating this unfortunate but easily avoidable mishap in nephrology
      practice.

PMID- 29225810
TI  - Achieving high convection volumes in postdilution online hemodiafiltration: a
      prospective multicenter study.
AB  - Background. Available evidence suggests a reduced mortality risk for patients
      treated with high-volume postdilution hemodiafiltration (HDF) when compared with
      hemodialysis (HD) patients. As the magnitude of the convection volume depends on
      treatment-related factors rather than patient-related characteristics, we
      prospectively investigated whether a high convection volume (defined as >=22
      L/session) is feasible in the majority of patients (>75%). Methods. A multicenter
      study was performed in adult prevalent dialysis patients. Nonparticipating
      eligible patients formed the control group. Using a stepwise protocol, treatment
      time (up to 4 hours), blood flow rate (up to 400 mL/min) and filtration fraction
      (up to 33%) were optimized as much as possible. The convection volume was
      determined at the end of this optimization phase and at 4 and 8 weeks thereafter.
      Results. Baseline characteristics were comparable in participants (n = 86) and
      controls (n = 58). At the end of the optimization and 8 weeks thereafter, 71/86
      (83%) and 66/83 (80%) of the patients achieved high-volume HDF (mean 25.5 +/- 3.6
      and 26.0 +/- 3.4 L/session, respectively). While treatment time remained
      unaltered, mean blood flow rate increased by 27% and filtration fraction
      increased by 23%. Patients with <22 L/session had a higher percentage of central
      venous catheters (CVCs), a shorter treatment time and lower blood flow rate when
      compared with patients with >=22 L/session. Conclusions. High-volume HDF is
      feasible in a clear majority of dialysis patients. Since none of the patients
      agreed to increase treatment time, these findings indicate that high-volume HDF
      is feasible just by increasing blood flow rate and filtration fraction.

PMID- 29225811
TI  - Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte
      profile.
AB  - Background: Cardiovascular disease is the most common cause of mortality in
      haemodialysis (HD) patients and is highly predicted by markers of chronic
      inflammation. Regular exercise may have beneficial anti-inflammatory effects, but
      this is unclear in HD patients. This study assessed the effect of regular
      intradialytic exercise on soluble inflammatory factors and inflammatory leucocyte
      phenotypes. Methods: Twenty-two HD patients from a centre where intradialytic
      cycling was offered thrice weekly and 16 HD patients receiving usual care
      volunteered. Exercising patients aimed to cycle for 30 min at rating of perceived
      exertion of 'somewhat hard'. Baseline characteristics were compared with 16
      healthy age-matched individuals. Physical function, soluble inflammatory markers
      and leucocyte phenotypes were assessed again after 6 months of regular exercise.
      Results: Patients were less active than their healthy counterparts and had
      significant elevations in measures of inflammation [interleukin-6 (IL-6), C
      reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), intermediate
      and non-classical monocytes; all P < 0.001]. Six months of regular intradialytic
      exercise improved physical function (sit-to-stand 60). After 6 months, the
      proportion of intermediate monocytes in the exercising patients reduced compared
      with non-exercisers (7.58 +/- 1.68% to 6.38 +/- 1.81% versus 6.86 +/- 1.45% to
      7.88 +/- 1.66%; P < 0.01). Numbers (but not proportion) of regulatory T cells
      decreased in the non-exercising patients only (P < 0.05). Training had no
      significant effect on circulating IL-6, CRP or TNF-alpha concentrations.
      Conclusions: These findings suggest that regular intradialytic exercise is
      associated with an anti-inflammatory effect at a circulating cellular level but
      not in circulating cytokines. This may be protective against the increased risk
      of cardiovascular disease and mortality that is associated with chronic
      inflammation and elevated numbers of intermediate monocytes.

PMID- 29225812
TI  - The utility of whole body vibration exercise in haemodialysis patients: a pilot
      study.
AB  - Background: Exercise improves physical capacity in patients with end-stage renal
      disease on haemodialysis (HD), but few patients engage in it. Whole-body
      vibration exercise (WBVE) is a novel protocol that has been shown to benefit
      frail elderly patients' rehabilitation. We assessed the utility of WBVE before HD
      sessions and tested methods to inform the design of a randomized controlled trial
      (RCT). Methods: Physical condition and quality of life were assessed at enrolment
      and repeated 2 weeks later in a pilot study of 49 patients undergoing regular HD.
      All patients then undertook 8 weeks of WBVE, thrice weekly for 3 min, after which
      the assessments were repeated and results compared (paired t-tests). Further
      assessments were made after a 4-week layoff. Patients completed a post-study
      questionnaire about their experiences of using WBVE. The reproducibility of WBVE
      and effects on measures of functionality, muscle strength, indirect exercise
      capacity, nutritional status, bone health and quality of life were recorded to
      undertake a power calculation for an RCT. Results: Of 49 patients enrolled, 25
      completed all assessments. The dropout rate was high at 49%, but overall, WBVE
      was an acceptable form of exercise. Functionality as assessed by the 60-s sit-to
      stand test (STS-60) improved significantly by 11% (P = 0.002). Some quality of
      life domains also improved significantly. All improvements were maintained 4
      weeks after discontinuing WBVE. Conclusions: WBVE was acceptable, safe, easily
      incorporated into the routine of HD and was associated with useful improvements
      in physical function sufficient to justify a RCT.

PMID- 29225813
TI  - Patient-perceived barriers to a screening program for depression: a patient
      opinion survey of hemodialysis patients.
AB  - Background: Depression is a prevalent, yet underdiagnosed, psychiatric disorder
      among patients with end-stage renal disease. Active case identification through
      routine screening is suggested; however, patient-related barriers may reduce the
      effectiveness of screening for, and treating, depression. This study aimed to
      explore the perceived barriers that limit patients from participating in
      screening and treatment programs for depression. Methods: In a cross-sectional
      study of chronic maintenance hemodialysis patients, the Perceived Barriers to
      Psychological Treatment questionnaire, adapted to include screening, was used to
      measure perceived barriers. The two-item Patient Health Questionnaire was used to
      identify patients with depressive symptoms. Results: Of 160 participants, 73.1%
      reported at least one barrier preventing them from participation [95% confidence
      interval (95% CI) 66.2-80.0%]. Patients with depressive symptoms were more likely
      to perceive at least one barrier to a screening program for depression compared
      with those without depressive symptoms (96% versus 68.9%, respectively; odds
      ratio = 10.8; 95% CI 1.4-82.8; P = 0.005). The association of the barrier scores
      with depressive symptoms remained significant after adjustment for patient's
      characteristics. The most common barriers that patients expressed were concerns
      about the side effects of any antidepressant medications that may be prescribed
      (40%), concerns about having more medications (32%), feeling that the problem is
      not severe enough (23%) and perceiving no risk of depression (23%). Conclusions:
      Negative perceptions about depression and its treatment among hemodialysis
      patients constitute an important barrier to identifying this condition and first
      need to be addressed before implementing a screening program in this population.

PMID- 29225814
TI  - Perioperative Plasma-Lyte use reduces the incidence of renal replacement therapy
      and hyperkalaemia following renal transplantation when compared with 0.9% saline:
      a retrospective cohort study.
AB  - Background: Kidney transplant recipients often receive large volumes of
      intravenous fluid replacement in the peri-operative period. Administration of
      0.9% saline has previously been associated with acidosis, hyperkalaemia and acute
      kidney injury. The perioperative use of physiologically balanced replacement
      fluids may reduce the incidence of post-operative renal replacement therapy and
      hyperkalaemia. Methods: A retrospective review of consecutive renal transplants
      before and after a change in perioperative fluid prescription from 0.9% saline to
      Plasma-Lyte 148. Results: A total of 97 patients were included in the study, 59
      receiving exclusively 0.9% saline and 38 receiving exclusively Plasma-Lyte.
      Patients in the Plasma-Lyte group were less likely to require emergency
      postoperative dialysis than those receiving 0.9% saline [odds ratio (OR) 0.15
      (95% confidence interval 0.03-0.48), P = 0.004], and these patients had more
      favourable biochemical parameters with less hyperkalaemia, less acidosis and
      better diuresis. Patients in the Plasma-Lyte group also had a shorter length of
      hospital stay (7 days versus 11 days; P < 0.0001) and better graft function at 3
      months postoperatively (estimated glomerular filtration rate 51 versus 44
      mL/min/1.73 m2; P = 0.03); however, there was no difference in graft function at
      1 year. Conclusions: Plasma-Lyte in the perioperative period is safe in renal
      transplantation and is associated with a favourable biochemical profile,
      including a reduced incidence of hyperkalaemia, better diuresis and less frequent
      use of renal replacement therapy early after surgery. In patients receiving
      Plasma-Lyte, graft function was better at 3 months, but this difference did not
      persist up to 1 year after transplantation.

PMID- 29225815
TI  - Hypercalcaemia preceding diagnosis of Pneumocystis jirovecii pneumonia in renal
      transplant recipients.
AB  - Background: The overall incidence of Pneumocystis jirovecii pneumonia (PJP) in
      solid organ transplant recipients is 5-15%. A timely diagnosis of PJP is
      difficult and relies on imaging and detection of the organism. Methods: We
      present a case series of four patients displaying hypercalcaemia with an eventual
      diagnosis of PJP and document the management of the outbreak with a
      multidisciplinary team approach. We discuss the underlying pathophysiology and
      previous reports of hypercalcaemia preceding a diagnosis of PJP. We also reviewed
      the evidence concerning PJP diagnosis and treatment. Results: Within our renal
      transplant cohort, four patients presented within 7 months with hypercalcaemia
      followed by an eventual diagnosis of PJP. We measured their corrected calcium,
      parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 25
      hydroxycholecalciferol [25(OH)D] levels at admission and following treatment of
      PJP. All four patients diagnosed with PJP were 4-20 years post-transplantation.
      Three of the four patients demonstrated PTH-independent hypercalcaemia (corrected
      calcium >3.0 mmol/L). The presence of high 1,25(OH)2D3 and low 25(OH)D levels
      suggest negation of the negative feedback mechanism possibly due to an extrarenal
      source; in this case, the alveolar macrophages. All four patients had resolution
      of their hypercalcaemia after treatment of PJP. Conclusions: Given the outbreak
      of PJP in our renal transplant cohort, and based on previous experience from
      other units nationally, we implemented cohort-wide prophylaxis with trimethoprim
      sulphamethoxazole for 12 months in consultation with our local infectious
      diseases unit. Within this period there have been no further local cases of PJP.

PMID- 29225816
TI  - Complement-dependent cytotoxicity and Luminex technology for human leucocyte
      antigen antibody detection in kidney transplant candidates exposed to different
      sensitizing events.
AB  - Background: The aim of this study was to determine the frequency of exposure to
      different sensitizing events (SEs) and to assess their effects on human leucocyte
      antigen (HLA) alloimmunization in transplant candidates using two different HLA
      antibody screening techniques: complement-dependent cytotoxicity (CDC) and
      Luminex. Methods: This retrospective study included HLA antibody screening
      results for 163 patients on the kidney transplant waiting list (WL) tested from
      March 2012 until the end of December 2015 at the Tissue Typing Laboratory,
      Rijeka, Croatia. All sera samples were tested using the CDC and Luminex
      techniques in parallel. Results: Two-thirds of the patients [114 (70%)] on the WL
      were exposed to transfusions, pregnancies and/or kidney transplant. The pre
      transplant sera of 104 (63.80%) patients were negative for antibodies. In the
      sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and
      in the sera of 36 (22.09%) patients by Luminex only. Conclusion: In patients on
      kidney WL, previous organ transplantation represents the strongest immunogenic
      stimulus, followed by blood transfusions (the most frequent SE) and pregnancies.
      Although Luminex is more sensitive than CDC in HLA antibody detection, the
      decision on unacceptable HLA antigens in WL patients has to be based on the
      results of both assays and the patient's immunization history.

PMID- 29225817
TI  - Interpretation of the Kidney Disease: Improving Global Outcomes guidelines for
      iron therapy: commentary and emerging evidence.
AB  - The 'Kidney Disease: Improving Global Outcomes' (KDIGO) Clinical Practice
      Guideline for Anaemia in Chronic Kidney Disease includes detailed recommendations
      for the use of iron therapy in a variety of clinical circumstances. However, the
      evidence base regarding the use of iron therapy in patients with chronic kidney
      disease was relatively incomplete at the time the guideline was developed. As a
      result, there has been significant debate as to the appropriate use of iron
      therapy in this population. In this article, the KDIGO guidelines are discussed
      in the context of recently published commentary pieces and additional research to
      provide a richer context in which to interpret and understand the guidelines.

PMID- 29225818
TI  - Practical considerations for iron therapy in the management of anaemia in
      patients with chronic kidney disease.
AB  - Clinical practice guidelines provide both local and global recommendations for
      the use of iron therapy in the management of anaemia in patients with chronic
      kidney disease. However, physicians must interpret and adapt these guidelines to
      meet the specific needs of their individual patients. The recommendations must
      also be considered in the context of findings from more recently published
      clinical trials and observational studies.

PMID- 29225819
TI  - Intravenous iron therapy in patients with chronic kidney disease: recent evidence
      and future directions.
AB  - Current recommendations for the use of intravenous iron therapy in the management
      of anaemia in patients with chronic kidney disease (CKD) are based on limited
      clinical evidence. Since the publication of the Kidney Disease: Improving Global
      Outcomes (KDIGO) Clinical Practice Guideline for Anaemia in Chronic Kidney
      Disease in 2012, a number of randomized clinical trials [notably, the Ferinject
      Assessment in Patients with Iron Deficiency Anaemia (FIND-CKD) and Randomized
      Trial to Evaluate IV and Oral Iron in Chronic Kidney Disease (REVOKE) trials] and
      observational studies have been completed, and a further large clinical trial
      Proactive IV Iron Therapy in Dialysis Patients (PIVOTAL)-is currently underway.
      In this article, the implications of the findings from these recent studies are
      discussed and the critical evidence gaps that remain to be addressed are
      highlighted.

PMID- 29225821
TI  - Erratum to "Rare benign mixed tumour of the upper lip: A case report" [Ann. Med.
      Surg. 4 (2015) 380-383].
AB  - [This corrects the article DOI: 10.1016/j.amsu.2015.10.001.].

PMID- 29225820
TI  - Iron therapy in heart failure patients without anaemia: possible implications for
      chronic kidney disease patients.
AB  - Iron deficiency anaemia is a global health problem that manifests as fatigue and
      poor physical endurance. Anaemia can be caused by dietary iron deficiency, blood
      loss or a combination of poor iron absorption and ineffective iron mobilization
      in patients with chronic disease. Nephrologists caring for patients with impaired
      renal function understand that iron treatment is necessary to provide adequate
      iron for erythropoiesis during the treatment of overt anaemia. However, a less
      well-understood health problem is iron deficiency, which creates symptoms that
      overlap with those of anaemia and often occurs in concert with chronic disease.
      Recently, several randomized controlled clinical trials have been conducted to
      investigate the effects of treatment with intravenous iron in heart failure
      patients with iron deficiency who may or may not also have anaemia. Given that
      heart and kidney disease are often comorbid, these clinical trials may have
      implications for the way nephrologists view their patients with iron deficiency.
      In this article, we review several clinical studies of intravenous iron therapy
      for patients with iron deficiency and heart failure and discuss possible
      implications for the treatment of patients with kidney disease.

PMID- 29225822
TI  - How to make an academic poster.
AB  - Academic posters are an excellent way to showcase your work at conferences and
      meetings. They can be used in poster presentations and serve as a summary of your
      project. In this how to article, we demonstrate how trainees can make and deliver
      a successful academic poster.

PMID- 29225825
TI  - Brain biopsy in the diagnosis of leptomeningeal involvement in stage I chronic
      lymphocytic leukemia.
AB  - Leptomeningeal involvement of CLL is usually underdiagnosed as neurological
      symptoms are unspecific. It is important to carefully evaluate neurological
      status in these patients and consider this entity between the differential
      diagnosis of a neurological deterioration as adequate treatment improves the
      prognosis. Imaging techniques, analyses of cerebrospinal fluid, and brain biopsy
      are useful to establish a definitive diagnosis.

PMID- 29225823
TI  - Human mitochondrial MTHFD2 is a dual redox cofactor-specific
      methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase.
AB  - Background: Folate-dependent one-carbon metabolism provides one-carbon units for
      several biological processes. This pathway is highly compartmentalized in
      eukaryotes, with the mitochondrial pathway producing formate for use in
      cytoplasmic processes. The mitochondrial enzyme MTHFD2 has been reported to use
      NAD+ as a cofactor while the isozyme MTHFD2L utilizes NAD+ or NADP+ at
      physiologically relevant conditions. Because MTHFD2 is highly expressed in many
      cancer types, we sought to determine the cofactor preference of this enzyme.
      Results: Kinetic analysis shows that purified human MTHFD2 exhibits dual redox
      cofactor specificity, utilizing either NADP+ or NAD+ with the more
      physiologically relevant pentaglutamate folate substrate. Conclusion: These
      results show that the mitochondrial folate pathway isozymes MTHFD2 and MTHFD2L
      both exhibit dual redox cofactor specificity. Our kinetic analysis clearly
      supports a role for MTHFD2 in mitochondrial NADPH production, indicating that
      this enzyme is likely responsible for mitochondrial production of both NADH and
      NADPH in rapidly proliferating cells.

PMID- 29225824
TI  - Robotic simultaneous resection of rectal cancer and liver metastases.
AB  - Surgical resection is the only potential cure for colorectal cancer with
      synchronous liver metastases (SLM). Simultaneous resection of colorectal cancer
      and SLM using robotic-assistance has been rarely reported. We demonstrate that
      robotic-assisted simultaneous resection of colorectal cancer and SLMs is
      feasible, safe, and has potential to demonstrate good oncologic outcomes.

PMID- 29225826
TI  - Subcutaneous defibrillator implantation as a bridge until left ventricular
      function normalizes.
AB  - Patients with reversible cardiac impairment may be, at least temporarily, at high
      risk of SCD and may go unprotected for considerable time. A less-invasive
      definitive or bridge solution is the implantation of a subcutaneous cardioverter
      defibrillator (S-ICD). The less invasiveness of this procedure ensures easy
      removal of the system without exposing the patient to the risk of complications.

PMID- 29225827
TI  - Gemcitabine and carfilzomib induced thrombotic microangiopathy: eculizumab as a
      life-saving treatment.
AB  - Drug-induced aHUS is rare; however, early diagnosis is vital to reduce morbidity
      and mortality. With confirmation of the diagnosis, eculizumab appears to be a
      viable treatment option to suppress the pro-inflammatory surge. Furthermore,
      adverse side effects of medications such as carfilzomib and gemcitabine should be
      considered in the appropriate settings.

PMID- 29225828
TI  - Cefepime-induced neurotoxicity in a pediatric patient on chronic hemodialysis: a
      case report.
AB  - Impaired renal function increases the risk for cefepime-induced neurotoxicity.
      Symptoms include disorientation, myoclonus, status epilepticus, ataxia, gait
      disturbance, coma, and death. A high index of suspicion and early recognition of
      symptoms can minimize the risk of progression of symptoms to permanent neurologic
      impairment or death.

PMID- 29225829
TI  - Surgical resection of adrenocortical carcinoma with invasion into the inferior
      vena cava: a case report and literature review.
AB  - Adrenocortical carcinoma (ACC) is a malignant endocrine tumor. Moreover, ACC with
      invasion into the inferior vena cava is rare. Early diagnosis and treatment are
      crucial for such cases. Radical surgical resection is the key therapeutic option
      in ACC.

PMID- 29225830
TI  - Acute basophilic leukemia associated with the t(16;21)(p11;q22)/FUS-ERG fusion
      gene.
AB  - We herein report a rare case of acute basophilic leukemia with t(16;21)(p11;q22)
      generating the FUS-ERG fusion gene. The basophilic nature of leukemia blasts was
      demonstrated by cytomorphology, toluidine blue metachromasia, mature basophil
      associated antigen expression, and characteristic granules under electron
      microscopy. The molecular link between t(16;21)/FUS-ERG and basophilic
      differentiation remains unclear.

PMID- 29225831
TI  - Delayed right ventricular lead perforation complicated by tamponade in
      biventricular hypertrophic cardiomyopathy.
AB  - This report highlights the importance of a more cautious approach in a patient
      with a history of implanted cardiac leads presenting with chest pain or dyspnea,
      to prevent overlooking cardiac lead perforations especially in hypertrophic
      cardiomyopathy which seems to be not absolutely protective.

PMID- 29225832
TI  - Corkscrew collaterals in atherosclerosis obliterans.
AB  - Marked calcifications in the femoral artery obscured imaging of the artery in
      computed tomography (CT) and duplex ultrasonography. The presence of corkscrew
      collateral arteries in patients with Atherosclerosis obliterans (ASO) indicates
      total artery occlusion.

PMID- 29225833
TI  - Longer recurrence-free survival in a patient with metastatic renal cell carcinoma
      treated with temsirolimus.
AB  - Temsirolimus did not demonstrate an efficacy advantage compared with sorafenib as
      second-line therapy in patients with metastatic renal cell carcinoma (mRCC). Only
      a few patients achieved complete responses, and the median progression-free
      survival rate remains short. We report one patient with mRCC who had a continuing
      response to temsirolimus.

PMID- 29225834
TI  - Thrombocytopenia and disseminated histoplasmosis in immunocompetent adults.
AB  - Disseminated histoplasmosis among immunocompetent patients is rare, but may be
      associated with clinically significant refractory thrombocytopenia. Platelet
      counts often return to normal levels following antifungal therapy. Therefore, the
      most important management of this refractory thrombocytopenia is the recognition
      and treatment of histoplasmosis infection.

PMID- 29225835
TI  - Supermicrosurgical replantation of a small amputated nasal tissue in a child.
AB  - This study reports a case of an 8-year-old boy who suffered from a dog bite
      injury to the nose. The amputated nasal tissue measured approximately 1.0 * 1.5
      cm and included part of the tip, alar, and soft triangle subunits. Both ends of
      an artery of less than 0.5 mm were found, and replantation was performed.
      Chemical leeching was performed postoperatively. At 5-year follow-up, a good
      aesthetic result was achieved.

PMID- 29225836
TI  - Cardiac tamponade occurred after endoscopic submucosal dissection: conservative
      management of the esophagopericardial fistula.
AB  - We describe the case of an esophagopericardial fistula generated after endoscopic
      submucosal dissection in a patient affected by a superficial esophageal squamous
      cell carcinoma immediately treated with percutaneous pericardial drainage and
      placement of a partially covered self-expanding metal stent that has been removed
      using the stent-in-stent technique after 35 days.

PMID- 29225837
TI  - The unusual case of the irretrievable colonoscope.
AB  - It is important that invasive procedures are rationalized, even relatively safe
      ones like colonoscopy, to minimize the risk of harm to patients.

PMID- 29225838
TI  - Multiple inappropriate implantable cardiac defibrillator therapies in rapid
      succession.
AB  - Inappropriate implantable cardiac defibrillator (ICD) shocks are associated with
      significant morbidity and have the potential to trigger ventricular arrhythmias,
      cardiac decompensation, and death. We present a case of multiple inappropriate
      ICD therapies in rapid succession due electromagnetic interference from a Dr-Ho's
      transcutaneous electric nerve stimulator machine, and subsequently from a faulty
      electrical outlet.

PMID- 29225839
TI  - A case of empyema and septic arthritis due to Nocardia farcinica.
AB  - Septic arthritis due to Nocardia sp. should be suspected when a patient with risk
      factors such as pneumoconiosis or diabetes mellitus develops joint symptoms,
      especially if the patient has had nocardiosis in other sites.

PMID- 29225840
TI  - Severe thyrotoxicosis in an infant revealing familial nonautoimmune
      hyperthyroidism with a novel (C672W) stimulating thyrotropin receptor germline
      mutation.
AB  - We describe severe thyrotoxicosis in young members of a family with nonautoimmune
      hyperthyroidism caused by a C672W germline mutation in exon 10 of TSHR gene. In
      this family, lack of genotype-phenotype correlation and anticipation across
      generations could be linked to an increased iodine intake as recently observed in
      France.

PMID- 29225841
TI  - Multiple large osteolytic lesions in a patient with systemic mastocytosis: a
      challenging diagnosis.
AB  - Patients with advanced variants of Systemic Mastocytosis may develop destructive
      bone lesions when massive mast cell (MC) infiltrates are present. Finding of
      large osteolyses in indolent systemic mastocytosis, typically characterized by
      low MC burden, should prompt investigations for an alternative explanation.

PMID- 29225842
TI  - How often is patent foramen ovale an innocent bystander?
AB  - Patent foramen ovale (PFO) is a risk factor for cryptogenetic stroke; its closure
      should be considered in selected patients. It is not always clear whether
      symptoms (presyncope, paresthesia) apparently due to paradoxical embolism are
      related with other cardiovascular disorders such as arrhythmias. Flecainide
      administration for post-PFO-closure supraventricular arrhythmias can unmask a
      latent undiagnosed Brugada syndrome.

PMID- 29225843
TI  - Rapid postoperative recurrence of a cranial multilobular tumor of bone in a young
      dog.
AB  - Although resection of multilobular tumors of bone can be associated with a good
      prognosis and long disease-free intervals in dogs, osteosarcomatous
      transformation should be considered a cause for rapid recurrence of clinical
      signs.

PMID- 29225844
TI  - Hemoglobin Providence (beta82 Lys > Asn, Asp) and lower-than-expected HbA1c in a
      nonadherent teenager with type 1 diabetes: a case report and literature review.
AB  - Endocrinologists should have a high index of suspicion for a Hb variant when the
      HbA1c is not consistent with other indices of glycemic control.

PMID- 29225845
TI  - Conservative treatment of a young adult patient with a moderate skeletal Class
      III malocclusion by applying the temporary anchorage devices and the surgically
      assisted rapid palatal expansion.
AB  - We present the orthodontic treatment of a 20-year-old Chinese man with the
      moderate skeletal Class III malocclusion. The usages of the temporary anchorage
      devices and the surgically assisted rapid palatal expansion (SARPE) have provided
      a variety of options for the treatment of Class III malocclusion.

PMID- 29225846
TI  - A rare and important case of Staphylococcus haemolyticus-associated ventricular
      atrial shunt nephritis.
AB  - Shunt nephritis is a rare and relatively new diagnosis involving glomerular
      kidney damage following ventriculoperitoneal and ventriculoatrial shunt
      placement. Our case report summarizes the presentation, diagnostic workup, and
      management of a patient with shunt nephritis. We also review and discuss the
      current literature on the topic.

PMID- 29225847
TI  - Coexistence of true talon cusp and double dens invaginatus in a single tooth: a
      rare case report and review of the literature.
AB  - Co-occurrence of a talon cusp and double dens invaginatus is an extremely rare
      developmental dental anomaly. This case report represents a talon cusp with two
      dens invaginatus on a maxillary right lateral incisor. Early identification is
      needed for prevention of potential problems on the affected or opposing tooth.

PMID- 29225848
TI  - Delayed diagnosis of Brugada syndrome in a patient with aborted sudden cardiac
      death and initial negative flecainide challenge.
AB  - A negative flecainide challenge does not rule out Brugada syndrome even in the
      presence of nonfatal cardiac arrest as the first manifestation of the disease.
      This should prompt clinicians to ensure long-term ECG follow-up and consider
      repeating a drug test with another sodium channel blocker.

PMID- 29225849
TI  - Severe pyoderma gangrenosum caused by myelodysplastic syndrome successfully
      treated with decitabine administered by a noncytotoxic regimen.
AB  - Pyoderma gangrenosum (PG) is a morbid necrotizing neutrophilic dermatoses for
      which current treatments are inadequate. Here, we describe the use of a novel
      noncytotoxic regimen of the deoxycytidine analog decitabine to treat underlying
      myeloid malignancy causing PG, to thereby produce safe and effective resolution
      of extensive PG.

PMID- 29225850
TI  - Newly developed atrial fibrillation progresses to a more severe INTERMACS score
      in a patient with advanced heart failure due to dilated cardiomyopathy.
AB  - We have presented a case of advanced HF, in which newly developed AF hastened the
      timing of the implantation of mechanical support. Newly developed AF in advanced
      HF may be intractable by medical therapies and could be a key event that
      determines the timing of mechanical support.

PMID- 29225851
TI  - Mitochondrial DNA mutation load in a family with the m.8344A>G point mutation and
      lipomas: a case study.
AB  - Studies have shown that difference in mtDNA mutation load among tissues is a
      result of postnatal modification. We present five family members with the
      m.8344A>G with variable phenotypes but uniform intrapersonal distribution of
      mutation load, indicating that there is no postnatal modification of mtDNA
      mutation load in this genotype.

PMID- 29225852
TI  - Physical rehabilitation modulates microRNAs involved in multiple sclerosis: a
      case report.
AB  - This study shows that neuromuscular taping improves gait, balance, pain and
      ability to walk and conduct daily activities in a multiple sclerosis patient. It
      is the first study to identify a panel of miRNAs modulated throughout
      rehabilitation using neuromuscular taping in a multiple sclerosis patient.

PMID- 29225853
TI  - A clinical picture of pulmonary embolism revealing light-chain myeloma.
AB  - We are highlighting on the particularity of a clinical picture of pulmonary
      embolism revealing light-chain myeloma in a 56-year-old male patient. Myeloma
      remains a rare affection. Even though its revelation through pulmonary embolism
      remains rare, it can be explained by hyperviscosity syndrome accompanying it.

PMID- 29225854
TI  - Tyrosine kinase inhibitor and rituximab-CHOP treatment for concurrent chronic
      myeloid leukemia and non-Hodgkin lymphoma: a case report.
AB  - Non-Hodgkin lymphoma can occur concurrently with chronic phase-chronic myeloid
      leukemia (CML) at initial diagnosis. Combination treatment with second-generation
      tyrosine kinase inhibitors and rituximab-CHOP for patients newly diagnosed with
      CML and non-Hodgkin lymphoma is effective for both diseases. However, we found
      that this treatment combination may induce severe myelosuppression.

PMID- 29225855
TI  - Uptake of home dialysis in younger adults: case studies that illustrate the
      multifaceted influence of home circumstances on dialysis decisions.
AB  - Younger adults considering home dialysis need support to ensure home
      circumstances are suitable and affordable. Home circumstances relate closely to
      the financial burden reported by younger home dialysis users. Attention to home
      circumstances of younger patients with chronic kidney disease by policymakers,
      funders, and healthcare practitioners is needed.

PMID- 29225856
TI  - Severe piperacillin-tazobactam-induced hemolysis in a cystic fibrosis patient.
AB  - Piperacillin-tazobactam is one of the most common causes of drug-induced immune
      hemolytic anemia (DIIHA) and is frequently utilized, especially in patients with
      cystic fibrosis (CF). Here, we report a case of life-threatening piperacillin
      tazobactam-associated DIIHA in a 30-year-old woman with CF and propose management
      recommendations for piperacillin-tazobactam-associated DIIHA in CF patients.

PMID- 29225857
TI  - PROS1 novel splice-site variant decreases protein S expression in patients from
      two families with thrombotic disease.
AB  - Our results prove that c.1871-14T>G is causative of type I PS deficiency,
      highlighting the importance of performing mRNA-based studies in order to evaluate
      variants pathogenicity. We evidence the increased risk of venous thromboembolism
      associated with this cryptic splice-site variant if present in patients with PS
      deficiency.

PMID- 29225858
TI  - Fatal CTLA-4 heterozygosity with autoimmunity and recurrent infections: a de novo
      mutation.
AB  - Primary immunodeficiency disorders are rarely diagnosed in adults but must be
      considered in the differential diagnosis of combined recurrent infections and
      autoimmune disease. We describe a patient with CTLA-4 haploinsufficiency and an
      abnormal regulatory T-cell phenotype. Unusually, infections were more severe than
      autoimmunity, illustrating therapeutic challenges in disease course.

PMID- 29225859
TI  - An unusual urinary tract infection in a healthy young man.
AB  - Appearances are deceptive. Prejudice sometimes will betray us. The key to making
      a diagnosis of infection with unknown focus is a focused interview and thorough
      physical examination. No special medical care is needed for transgender
      individuals, although medical staff should be aware that some individuals might
      have special requirements.

PMID- 29225860
TI  - Massive hemorrhage following definitive esophageal chemoradiation: teaching case
      of a fatal aortoesophageal fistula and lessons learned.
AB  - Esophageal self-expandable metal stents and radiotherapy are valuable in
      combination for palliation and definitive treatment of esophageal cancer.
      However, risk of aortoesophageal fistula is significant in patients with evidence
      of malignant aortic invasion. Use of thoracic endovascular repair may represent
      an approach to early intervention in high-risk patients.

PMID- 29225861
TI  - Accidental knotting and subsequent removal of a catheter from the epidural space
      in an adult cow: a case report.
AB  - This is the first reported case in the veterinary literature of a knot in an
      epidural catheter. The report reviews this very rare complication and describes
      options for investigation and retrieval of catheters entrapped in the epidural
      space of any species.

PMID- 29225862
TI  - Hitherto unseen survival in an ALK-positive-patient with advanced stage adult
      ganglioneuroblastoma treated with personalized medicine.
AB  - Survival of stage 4 ganglioneuroblastoma (GNB) patients is poor; no reports exist
      of patients surviving up to 5 years (1, 2). We report the clinical and
      therapeutic course of a patient with stage 4 GNB surviving beyond expectations
      due to a multimodal treatment approach incorporating new technologies in cancer
      diagnostic and treatment.

PMID- 29225863
TI  - Acute total occlusion of the left main coronary artery treated with percutaneous
      intervention and simultaneous implantation of intra-aortic balloon pump.
AB  - Electrocardiographic findings at first medical contact and direct transfer to the
      catheterization laboratory are important in acute total occlusion of the left
      main coronary artery. Simultaneous emergency angioplasty and intra-aortic balloon
      pump implantation might be beneficial in overcoming the patient's most critical
      hemodynamic instability.

PMID- 29225864
TI  - Simultaneous laparoscopic cholecystectomy and transabdominal preperitoneal
      hernioplasty: two case reports evaluate the safety and surgical complications.
AB  - The safety of combining transabdominal preperitoneal (TAPP) hernioplasty and
      cholecystectomy in one laparoscopic surgery is still for many years questionable.
      We report two cases describing the safety and discussing the main concerns
      regarding the complications. As there are only few cases discuss this kind of
      combination, we aim to further clarify this subject to provide the best practice
      for our patients.

PMID- 29225866
TI  - Magnetic-guided catheter ablation of twin AV nodal reentrant tachycardia in a
      patient with left atrial isomerism, interrupted inferior vena cana, and Kawashima
      Fontan procedure.
AB  - Twin AV nodal reentrant tachycardia most commonly occurs in patients with complex
      congenital heart disease who have two distinct AV nodes, His bundles, and non
      preexcited QRS morphologies. Catheter ablation of the weaker AV node may be
      hindered by anatomical complexities. In such cases, remote magnetic guidance
      offers a potentially effective solution.

PMID- 29225865
TI  - Hypoglycemia and severe lactic acidosis in a dog following metformin exposure.
AB  - Hypoglycemia and lactic acidosis are rare complications with metformin use in
      humans. As metformin is not commonly used in veterinary medicine, severe adverse
      effects secondary to exposure are not known. Awareness of potentially life
      threatening complications with metformin exposure is an important addition to the
      veterinary literature.

PMID- 29225867
TI  - Visceral leishmaniasis triggering an adult-onset Still's disease: a unique case.
AB  - Adult-onset Still's disease (AOSD) due to visceral leishmaniasis (VL) has not
      been previously reported. This case report analyzes a single episode of AOSD
      probably due to a visceral leishmaniasis successfully treated with pentamidine
      isethionate and prednisone.

PMID- 29225868
TI  - Extra-pulmonary primary small-cell neuroendocrine carcinoma arising from the
      duodenum: rare tumor, unusual location.
AB  - Small-cell neuroendocrine carcinoma is a high-grade carcinoma rarely encountered
      in extra-pulmonary sites. A 40-year-old lady presented with epigastric pain and
      was noted to have an ulcerated small-cell neuroendocrine carcinoma in her
      duodenum with liver metastases. She underwent palliative chemotherapy but
      unfortunately passed away. Duodenal SCNC is an unusual malignancy with an
      aggressive phenotype.

PMID- 29225869
TI  - Spontaneous tumor lysis syndrome in colon cancer: a case report and literature
      review.
AB  - Although tumor lysis syndrome is well described, it is rarely seen or suspected
      in solid malignancies. Early recognition of this entity is paramount in reducing
      morbidity and mortality. Treating physicians should be aware of this possibility
      in solid tumor patients with either bulky disease or extensive liver involvement.

PMID- 29225870
TI  - Prostate cancer infiltrating the bladder sphincter successfully treated with
      Electrochemotherapy: a case report.
AB  - We demonstrate feasibility and safety of Electrochemotherapy for treatment of a
      prostate cancer (PCa) with infiltration of the urethral sphincter. The patient
      remained continent and potent, toxicity was low, and 6 months of follow-up showed
      no cancer activity. We conclude that Electrochemotherapy should be further
      evaluated as treatment strategy for locally advanced PCa.

PMID- 29225871
TI  - The application of catheter ablation in a rare case with coughing-induced
      supraventricular tachyarrhythmias.
AB  - Coughing could induce symptomatic, frequent atrial premature contractions (APCs),
      and episodes of atrial tachycardia (AT) in a rare case. If multiple arrhythmic
      drugs therapy failed to control the symptoms, catheter ablation was an effective
      therapeutic option for abolishing such atrial tachyarrhythmias guided by the
      electroanatomic mapping systems.

PMID- 29225872
TI  - Acute psychotic symptoms following a single dose of levofloxacin.
AB  - The objective of our case report was to raise awareness of the neurotoxic
      potential of levofloxacin in naive patients. In patients with severe infections
      and comorbidities, it would be difficult to discriminate the neurotoxic effects
      of levofloxacin from those of the medical condition itself. Thus, health
      professionals should be aware of the early onset CNS effects of levofloxacin in
      naive patients.

PMID- 29225873
TI  - Migration of emboli in the retinal artery: case report.
AB  - Branch retinal artery occlusion (BRAO) is a prevalent vascular occlusive disorder
      of the eye. In transient BRAO, an embolus temporarily blocks the vessel and then
      moves on resulting in recovery of blood circulation. In this case, we have
      documented migration of the embolus with recovery of perfusion of the retina and
      improvement of visual acuity in a patient with transient BRAO. Early diagnosis
      and fast action are important in the case of patients with retinal artery
      occlusion.

PMID- 29225874
TI  - Patterns of vascular calcification in patients with end-stage renal disease and
      calcific uremic arteriolopathy.
AB  - Calcific uremic arteriolopathy or calciphylaxis is a rare and potentially fatal
      condition, which manifests as skin ischemia and necrosis, usually seen in
      patients with end-stage renal disease. It is frequently associated with vascular
      calcification visible on plain radiographs, which can occur in various patterns.

PMID- 29225875
TI  - An 88-year-old patient with ADPKD: underscoring the importance of risk factor
      modification.
AB  - The mean age of onset of end-stage renal disease (ESRD) in autosomal dominant
      polycystic kidney disease (ADPKD) is between 56 and 69. Our case represents one
      of the oldest patients with ADPKD, whose chronic kidney disease (CKD) progression
      rate could be successfully reduced by optimal risk factor modification.

PMID- 29225876
TI  - Asymptomatic giant retroperitoneal mass detected at a medical checkup.
AB  - The differential diagnosis of retroperitoneal mass includes liposarcoma,
      leiomyosarcoma, malignant fibrous histiocytoma, neurofibroma, stromal tumor,
      teratoma, and lymphoma. Leiomyosarcoma is rare with poorer prognosis than other
      soft tissue sarcomas. Soft tissue sarcoma of retroperitoneal origin often remains
      asymptomatic until tumor enlargement, leading to diagnosis at advanced stages.

PMID- 29225877
TI  - Hirayama disease: diagnostic essentials in neuroimaging.
AB  - A 22-year-old male presented with progressive muscular weakness of the upper
      extremities. MRI of the cervical spine established the final diagnosis of
      Hirayama disease (HD). HD is a rare disease with benign progress. Neurologists
      and radiologists should be aware of the specific neuroimaging signs of this rare
      clinical entity.

PMID- 29225878
TI  - Erdheim-Chester Disease with atrial mass and perinephric calcification.
AB  - Erdheim-Chester Disease is a multi-systemic condition characterized by non
      Langerhans histiocytic infiltration. Cardiovascular involvement with
      pseudotumoral infiltration of the right atrium is present in approximately one
      third of patients and may be asymptomatic. Although retroperitoneal fibrosis is
      common, perinephric dystrophic calcification has not been previously described.

PMID- 29225879
TI  - Change in bowel habit, abdominal pain, and a palpable abdominal mass in a 58-year
      old female.
AB  - Giant colonic diverticulum is a rare complication of diverticulosis, which may
      present in the acute or chronic setting. Colonic resection and en bloc resection
      of the diverticulum are the favored management, however, conservative treatment
      remains an option that could be considered in asymptomatic patients with minimal
      symptoms.

PMID- 29225880
TI  - Tumor lysis syndrome with massive hyperphosphatemia and hyperuricemia.
AB  - Tumor lysis syndrome (TLS) occurs when tumor cells release their contents into
      the bloodstream, typically in response to chemotherapy, leading to the
      characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia,
      hypocalcemia, and acute kidney injury. Twinkle artifacts on renal ultrasound may
      indicate calcium phosphate deposits in such patients.

PMID- 29225881
TI  - Recovery benefits of using a heat and moisture exchange mask during sprint
      exercise in cold temperatures.
AB  - Objectives: Breathing cold air can lead to bronchoconstriction and peripheral
      vasoconstriction, both of which could impact muscular performance by affecting
      metabolic demands during exercise. Successful solutions dealing with these
      physiological changes during exercise in the cold has been lacking; therefore, we
      investigated the influence of a heat and moisture exchange mask during exercise
      in the cold. Methods: There were three trial arms within this study: wearing the
      heat and moisture exchange mask during the rest periods in the cold, no-mask
      application during the rest periods in the cold, and a trial at room temperature
      (22 degrees C). Eight subjects cycled in four 35 kJ sprint sessions with each
      session separated by 20 min rest period. Workload was 4% of body mass. Results:
      Mean sprint times were faster with heat and moisture exchange mask and room
      temperature trial than cold, no-mask trial (133.8 +/- 8.6, 134.9 +/- 8.8, and
      138.0 +/- 8.4 s (p = 0.001)). Systolic blood pressure and mean arterial pressure
      were greater during the cold trial with no mask (15% and 13%, respectively), and
      heart rate was 10 bpm less during the third rest or recovery period during cold,
      no mask compared to the heat and moisture exchange mask and room temperature
      trials. Subjects demonstrated significant decreases in vital capacity and peak
      expiratory flow rate during the cold with no mask applied during the rest
      periods. Conclusions: These negative responses to cold exposure were alleviated
      by the use of a heat and moisture exchange mask worn during the rest intervals by
      minimizing cold-induced temperature stress on the respiratory system with
      subsequent maintenance of cardiovascular function.

PMID- 29225882
TI  - Resection of unicentric interlobar Castleman disease with following adjuvant
      radiotherapy.
AB  - A 22-year-old female patient with rare interlobar unicentric Castleman disease is
      presented. The tumour was discovered incidentally and thoracoscopic biopsy was
      planned to rule out malignancy. Due to dense adhesions to the adjacent anatomical
      structures and diffuse bleeding when mobilizing the tumour, a thoracoscopic
      approach was converted to thoracotomy. The tumour was removed without lung
      resection. Adjuvant radiotherapy was used to avoid possible recurrence of the
      disease. During the follow-up of 6 years, the patient remains free of any
      symptoms and evidence of recurrence.

PMID- 29225883
TI  - Fullerenes in Biology and Medicine.
AB  - Fullerenes and related carbon based derivatives have shown a growing relevance in
      biology and medicine, mainly due to the unique electronic and structural
      properties that make them excellent candidates for multiple functionalization.
      This review focuses on the most recent developments of fullerene derivatives for
      different biological applications.

PMID- 29225884
TI  - SETBP1 mutations as a biomarker for myelodysplasia /myeloproliferative neoplasm
      overlap syndrome.
AB  - Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been
      described since the 2001 WHO classification as disorders that have both
      proliferative and dysplastic changes simultaneously. Specific disorders include
      chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML),
      BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable
      MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been
      described. Among them, SETBP1 mutations have been identified in up to 32% of
      aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients. The mutation
      hotspot lies in the amino acid residues 858-871 in the SETBP1 protein. SETBP1
      mutations in MDS/MPN overlap syndrome is associated with accelerated
      transformation to leukemia and poor prognosis. In this review, we summarized the
      latest data on the role of SETBP1 mutations in the overlap syndrome. SETBP1
      mutations may serve as a biomarker for the diagnosis and poor prognosis of the
      overlap syndrome.

PMID- 29225885
TI  - Life-history strategy, resource dispersion and phylogenetic associations shape
      dispersal of a fig wasp community.
AB  - Background: The combined influence of life-history strategy and resource
      dispersion on dispersal evolution of a biological community, and by extension, on
      community assemblage, has received sparse attention. Highly specialized fig wasp
      communities are ideal for addressing this question since the life-history
      strategies that affect their pace of life and the dispersion of their oviposition
      resources vary. We compared dispersal capacities of the wasp community of a
      widespread tropical fig, Ficus racemosa, by measuring flight durations, somatic
      lipid content and resting metabolic rates. Results: Wasp species exhibiting
      greater flight durations had higher energy reserves and resting metabolic rates.
      "Fast"-paced species showed higher dispersal capacities reflecting requirements
      for rapid resource location within short adult lifespans. Longer-lived "slow"
      paced species exhibited lower dispersal capacities. Most dispersal traits were
      negatively related with resource dispersion while their variances were positively
      related with this variable, suggesting that resource dispersion selects for
      dispersal capacity. Dispersal traits exhibited a phylogenetic signal.
      Conclusions: Using a combination of phylogeny, trait functionality and community
      features, we explain how dispersal traits may have co-evolved with life-history
      strategies in fig wasps and influenced a predisposition for dispersal. We
      speculate how processes influencing dispersal trait expression of community
      members may affect resource occupancy and community assemblage.

PMID- 29225886
TI  - Correction to: A cross-validation-based approach for delimiting reliable home
      range estimates.
AB  - [This corrects the article DOI: 10.1186/s40462-017-0110-4.].

PMID- 29225887
TI  - A prospective, longitudinal, study of men with borderline personality disorder
      with and without comorbid antisocial personality disorder.
AB  - Background: Some evidence suggests that the prevalence of Borderline Personality
      Disorder (BPD) is elevated among male criminal offenders. It is not presently
      known whether offending, and violent offending, are limited to those presenting
      comorbid Antisocial Personality Disorder (ASPD) who have a childhood history of
      conduct problems and whether offending is linked to psychopathic traits. Methods:
      A community sample of 311 males followed from age 6 to 33 years, one third of
      whom had a criminal charge between ages 18 and 24, completed diagnostic
      interviews and the Psychopathy Checklist-Revised interview. Information on
      childhood included parent-reported family characteristics and teacher-rated of
      hurtful and uncaring behaviours, conduct problems, hyperactivity and inattention,
      and anxiety at age 6, 10, and 12 years. Health files were obtained as were
      records of criminal convictions from age 12 to 33. Results: At age 33, 4% of the
      men presented BPD and not ASPD, 16% ASPD and not BPD, 8% BPD + ASPD, and 72%
      neither disorder (ND). Comorbid disorders were common: BPD were distinguished by
      high levels of anxiety disorders, BPD and BPD + ASPD by depression disorders, and
      BPD, BPD + ASPD, and ASPD by substance dependence. Official files indicated use
      of health services by all participants. One-third of participants with BPD and
      BPD + ASPD acquired a diagnosis of a personality disorder. More than one-third of
      participants with BPD + ASPD obtained scores indicative of the syndrome of
      psychopathy. Convictions for violent crimes varied across groups: In adolescence,
      BPD none, BPD + ASPD 16%, ASPD 16%, and ND 3.6%; from age 18 to 33, BPD 18%, ASPD
      19%, BPD + ASPD 52%, and ND 4.4%. Offenders with BPD + ASPD were convicted, on
      average, for four times more violent crimes than offenders with ASPD and seven
      times more than ND offenders. In childhood, men with BPD + ASPD and with ASPD had
      obtained similarly elevated ratings for disruptive behaviours as compared to ND.
      Conclusion: BPD comorbid with ASPD was associated with violent criminal offending
      in adolescence and most strongly in adulthood, elevated levels of psychopathic
      traits, and childhood disruptive behaviour. BPD showed similar characteristics
      but to a much less degree.

PMID- 29225888
TI  - Contribution to diagnosis and treatment of bone marrow aspirate results in
      critically ill patients undergoing bone marrow aspiration: a retrospective study
      of 193 consecutive patients.
AB  - Background: The purpose of the work was to assess the contribution to diagnosis
      and/or treatment (CDT) of bone marrow aspiration (BMA) in the critically ill
      patient. Methods: The retrospective study included 193 patients. On the basis of
      BMA findings, contribution to diagnosis was defined by one of four previously
      unestablished diagnoses (maturation arrest of granulocyte precursors,
      hemophagocytic lymphohistiocytosis, hematological malignancy, marrow infiltration
      with cancer cells) and to treatment as the initiation or withdrawal of a specific
      treatment including the decision to forgo life-sustaining treatment (DFLST).
      Results: A CDT of BMA was observed in 40/193 patients (20.7%). BMA contributed to
      diagnosis in 37 cases (granulocyte precursor maturation arrest, N = 10;
      hemophagocytic lymphohistiocytosis, N = 12; hematological malignancy, N = 15) and
      to treatment in 14, including three DFLSTs. In multivariate analysis, the factors
      associated with a CDT were hematological malignancy, cancer or non-malignant
      hematological abnormality known on admission, indication for BMA excluding
      isolated thrombocytopenia, higher pre-BMA HScore (calculated prior to BMA), and
      higher SOFA score with or without platelet-count SOFA subscore. In the 160
      patients without hematological malignancy or cancer known on admission, non
      malignant hematological abnormality known on admission, indication for BMA
      excluding isolated thrombocytopenia, higher pre-BMA HScore, and higher SOFA score
      calculated with or without platelet-count SOFA subscore were independently
      associated with a CDT of BMA. Conclusion: BMA can have a significant CDT in ICU
      patients with or without a known hematological malignancy or cancer on admission.
      An HScore calculated before BMA can be a valuable tool for predicting a CDT of
      BMA.

PMID- 29225889
TI  - Efficacy of sonographic and biological pleurodesis indicators of malignant
      pleural effusion (SIMPLE): protocol of a randomised controlled trial.
AB  - Introduction: Malignant pleural effusion (MPE) is common and currently in UK
      there are an estimated 50 000 new cases of MPE per year. Talc pleurodesis remains
      one of the most popular methods for fluid control. The value of thoracic
      ultrasound (TUS) imaging, before and after pleurodesis, in improving the quality
      and efficacy of care for patients with MPE remains unknown. Additionally,
      biomarkers of successful pleurodesis including measurement of pleural fluid
      proteins have not been validated in prospective studies.The SIMPLE trial is an
      appropriately powered, multicentre, randomised controlled trial designed to
      assess 'by the patient bedside' use of TUS imaging and pleural fluid analysis in
      improving management of MPE. Methods and analysis: 262 participants with a
      confirmed MPE requiring intervention will be recruited from hospitals in UK and
      The Netherlands. Participants will be randomised (1:1) to undergo either chest
      drain insertion followed by instillation of sterile talc, or medical thoracoscopy
      and simultaneous poudrage. The allocated procedure will be done while the patient
      is hospitalised, and within 3 days of randomisation. Following hospital
      discharge, participants will be followed up at 1, 3 and 12 months. The primary
      outcome measure is the length of hospital stay during initial hospitalisation.
      Ethics and dissemination: The trial has received ethical approval from the South
      Central-Oxford C Research Ethics Committee (Reference number 15/SC/0600). The
      Trial Steering Committee includes an independent chair and members, and a patient
      representative. The trial results will be published in a peer-reviewed journal
      and presented at international conferences. Trial registration number: ISRCTN:
      16441661.

PMID- 29225890
TI  - Can peer support be cost saving? An economic evaluation of RAPSID: a randomized
      controlled trial of peer support in diabetes compared to usual care alone in East
      of England communities.
AB  - Background: Diabetes peer support, where one person with diabetes helps others,
      may improve diabetes management. The objective of this study was to perform a
      cost analysis of peer support strategies used in RAndomized controlled trial of
      Peer Support in type 2 Diabetes. Methods: We performed a 2*2 factorial randomized
      cluster controlled trial in England. People with type 2 diabetes were invited to
      participate as either 'peer' or 'peer support facilitator' (PSF) through postal
      invitation predominantly from general practice. Clusters, based on local
      communities, were each randomly assigned to one arm of group, 1:1, both group and
      1:1 or control interventions. The intervention was delivered over 8-12 months by
      trained PSFs, supported by monthly meetings with a diabetes nurse. Out-of-pocket
      expenses/service utilization were self-reported at baseline, midpoint and on
      trial completion. Intervention costs were collated. Non-hospital costs used
      National Health Service (NHS) reference costs. Hospital payments were obtained
      from one local commissioning group and mean payments calculated. The analysis
      employed a societal perspective. Costs were evaluated at the conclusion of the
      trial. Results: Participants (n=1299) were recruited across 130 clusters. The
      four arms were well balanced and matched (60% male, mean diabetes duration 9.5
      years, mean glycated haemoglobin (HbA1c) 7.4+/-1.3%, 17% insulin treated).
      Implementation costs at 2013 rates were L13.84/participant/annum, participant out
      of-pocket expenses for any intervention were L11.41/participant/annum and the NHS
      incurred costs were reduced by L138.38/participant/annum. Savings for the 1:1,
      group and any intervention were L233.65, L90.52 and L113.13/participant/annum,
      respectively. Conclusions: We conclude that both 1:1 and group diabetes peer
      support over 8-12 months are cost saving in this setting, although much of the
      benefit is largely derived by differences in self-reported healthcare
      utilization. Long-term benefits should be investigated. Trial registration
      number: ISRCTN66963621.

PMID- 29225891
TI  - Evaluation of a type 2 diabetes prevention program using a commercial weight
      management provider for non-diabetic hyperglycemic patients referred by primary
      care in the UK.
AB  - Objectives: To determine if a diabetes prevention program (DPP) delivered by a
      commercial weight management provider using a UK primary care referral pathway
      could reduce the progression to type 2 diabetes (T2D) in those diagnosed with non
      diabetic hyperglycemia (NDH-being at high risk of developing T2D). Research
      design: This is a quasi-experimental translational research study. Methods: 14
      primary care practices identified, recruited and referred patients with NDH
      (fasting plasma glucose >=5.5 to <=6.9 mmol/L and/or glycated hemoglobin (HbA1c)
      >=42 to 47 mmol/mol (6.0%-6.4%)) and a body mass index (BMI) >=30 kg/m2 to a DPP.
      Eligible patients were asked to contact Weight Watchers to book onto their DPP,
      an intensive lifestyle intervention which included a 90 min activation session
      followed by the offer of 48 weekly Weight Watchers community group meetings.
      Patients' blood tests were repeated by primary care, weight change plus self
      reported data was recorded by Weight Watchers. Results: 166 patients were
      referred to the program and 149 were eligible. 79% of eligible patients attended
      an activation session (117 eligible patients) and 77% started the weekly
      sessions. The study sample was primarily female (75%), white (90%), with 5%
      living in the most deprived quintile in the UK. Using intention-to-treat
      analysis, the DPP resulted in a mean reduction in HbA1c of 2.84 mmol/mol at 12
      months (from 43.42+/-1.28 to 40.58+/-3.41, p<0.01). 38% of patients returned to
      normoglycemia and 3% developed T2D at 12 months. There was a mean weight
      reduction in BMI of 3.2 kg/m2 at 12 months (35.5 kg/m2+/-5.4 to 32.3 kg/m2+/-5.2,
      p<0.01). Conclusion: A UK primary care referral route partnered with this
      commercial weight management provider can deliver an effective DPP. The lifestyle
      changes and weight loss achieved in the intervention translated into considerable
      reductions in diabetes risk, with an immediate and significant public health
      impact.

PMID- 29225892
TI  - Correlates of second-line type 2 diabetes medication selection in the USA.
AB  - Objective: Past research provides insufficient evidence to inform second-line
      diabetes medication prescribing when metformin is no longer sufficient. We
      evaluated patient, prescriber, and health plan characteristics associated with
      selection of second-line diabetes medications in the USA. Research design and
      methods: We used a multiple case-comparison study design to identify
      characteristics associated with the probability of starting each of six second
      line diabetes medication alternatives within 77 744 adults enrolled in commercial
      or Medicare Advantage health plans from 2011 to 2015. National administrative
      data were provided by a large commercial health payer. Multinomial logistic
      regression models were used to identify characteristics independently associated
      with selecting each diabetes drug class. Results: From 2011 to 2015,
      sulfonylureas still represented 47% of all second-line drug starts, with
      proportionately higher use in patients >=75 years of age (63% of drug starts).
      Basal insulin was more likely to be selected when a past A1c test result was >10%
      (13.0% vs 4.5% for those with A1c <8%; p<0.001). Initiation of a glucagon-like
      peptide-1 receptor agonist was associated with being female (10.1% vs 6.0% for
      male; p<0.001) and having a diagnosis code for obesity (10.8% vs 6.9% for no
      diagnosis; p<0.001). For all drug classes, the recent prescribing behavior of the
      provider was a strong correlate of subsequent second-line drug selection.
      Conclusions: Sulfonylureas continue to represent almost half of second-line
      diabetes medication starts in the USA. This could reflect overuse for some groups
      such as older adults, for whom some alternatives may be safer, although more
      costly and potentially less effective. Future research should compare outcomes of
      medication choices and conditions under which particular classes are most
      effective.

PMID- 29225893
TI  - A novel approach to glycemic control in type 2 diabetes mellitus, partial jejunal
      diversion: pre-clinical to clinical pathway.
AB  - Objective: To explore partial jejunal diversion (PJD) via a side-to-side jejuno
      jejunostomy for improved glycemic control in type 2 diabetes mellitus (T2DM). PJD
      is an anatomy-sparing, technically simple surgery in comparison to the
      predominate metabolic procedures, Roux-en-Y gastric bypass (RYGB) and sleeve
      gastrectomy (SG). Positive results in a rodent model prompted a human proof-of
      concept study. Research design and methods: Pre-clinically, 71 rats were studied
      in a model of metabolic dysfunction induced by a high-fat diet; 33 animals
      undergoing one of two lengths of PJD were compared with 18 undergoing sham, 10
      RYGB and 10 jejuno-ileal bypass. Clinically, 15 adult subjects with treated but
      inadequately controlled T2DM (hemoglobin A1c (HbA1c) of 8.0%-11.0%), body mass
      index of 27.0-40.0 kg/m2, and C peptide >=3 ng/mL were studied. Follow-up was at
      2 weeks, and 3, 6, 9, and 12 months post-PJD. Results: Pre-clinically, positive
      impacts with PJD on glucose homeostasis, cholesterol, and body composition versus
      sham control were demonstrated. Clinically, PJD was performed successfully
      without serious complications. Twelve months post-surgery, the mean (SD)
      reduction from baseline in HbA1c was 2.3% (1.3) (p<0.01). Conclusions: PJD may
      provide an anatomy sparing, low-risk, intervention for poorly controlled T2DM
      without significant alteration of the patient's lifestyle. The proof-of-concept
      study is limited by a small sample size and advanced disease, with 80% of
      participants on insulin and a mean time since diagnosis of over 10 years. Further
      study is warranted. Trial registration number: NCT02283632; Pre-results.

PMID- 29225894
TI  - Adolescents' perceptions of participation in group education using the Guided
      Self-Determination-Young method: a qualitative study.
AB  - Objective: Guided Self-Determination (GSD) is a person-centered communication and
      reflection method. Education in groups may have a greater impact than the content
      of the education, and constructive communication between parents and adolescents
      has been shown to be of importance. The purpose of this study was to describe
      adolescents' perceptions of participation in group education with the Guided Self
      Determination-Young (GSD-Y) method, together with parents, in connection with the
      introduction of continuous subcutaneous insulin infusion. Research design and
      methods: In the present qualitative interview study, 13 adolescents with type 1
      diabetes were included after completing a GSD-Y group education program in
      connection with the introduction of continuous subcutaneous insulin infusion at
      three hospitals located in central Sweden. The adolescents were interviewed
      individually, and qualitative content analysis was applied to the interview
      transcripts. Results: Two categories that emerged from the analysis were the
      importance of context and growing in power through the group process. An
      overarching theme that emerged from the interviews was the importance of expert
      and referent power in growing awareness of the importance of self-management as
      well as mitigating the loneliness of diabetes. Conclusions: GSD-Y has, in various
      ways, mitigated experiences of loneliness and contributed to conscious reflection
      about self-management in the group (referent power) together with the group
      leader (expert power). Overall, this highlights the benefits of group education,
      and the GSD method emphasizes the person-centered approach. Trial registration
      number: ISRCTN22444034; Results.

PMID- 29225895
TI  - Higher health literacy is associated with better glycemic control in adults with
      type 1 diabetes: a cohort study among 1399 Danes.
AB  - Aim: Self-management of diabetes is influenced by a range of factors including
      the ability to access, understand, appraise, and use of health information in
      everyday life, which can collectively be called health literacy. We investigated
      associations between nine domains of health literacy and HbA1c level in people
      with type 1 diabetes. Methods: A cross-sectional study was conducted with 1399
      people with type 1 diabetes attending a Danish specialist diabetes clinic. Health
      literacy was assessed using the nine-domain Health Literacy Questionnaire. The
      association between health literacy and HbA1c was analyzed using linear
      regression with adjustment for age, sex, educational attainment and diabetes
      duration. Results: Of the 1399 participants, 50% were women, mean age was 54
      years, and mean HbA1c was 61 mmol/mol (7.8%). Higher health literacy scores were
      associated with lower HbA1c levels across eight of nine health literacy domains.
      This association remained significant after adjusting for educational attainment.
      Among the domains, 'Actively managing my health' had the strongest impact on
      HbA1c. This was in turn predicted by 'Appraising health information', 'Having
      sufficient information to manage health', and 'Social support for health'.
      Conclusions: Higher health literacy levels are associated with lower HbA1c
      regardless of educational background. This study highlights the importance of
      healthcare provision to respond to the health literacy levels of people with
      diabetes and to the possible need to provide program designed to enhance health
      literacy.

PMID- 29225897
TI  - 'Bottom-hung window' trauma in cats: neurological evaluation and outcome in 71
      cats with bilateral hindlimb injury.
AB  - Objectives: Influence of neurological status on the mortality rate of
      paraparetic/paralysed cats presenting after entrapment in a bottom-hung window
      was evaluated. It was hypothesised that (1) loss of deep pain sensation at
      admission would not be a negative prognostic factor for regaining motor function
      and that (2) mortality rate would be influenced by the severity of neurological
      grade upon admission. Methods: Clinical and pathological data of affected cats
      that presented at our institution between 2001 and 2012 for this specific trauma
      were collected retrospectively: breed, age, sex, last contact with owner (<3
      hours and >3 hours), whether the cat was suffering from monoparesis or
      paraparesis/paraplegia, duration of hospitalisation, rectal temperature, surface
      temperature of the skin of the hindlimbs, femoral pulse and tone of the pelvic
      musculature. Neurological status was categorised according to Scott's
      classification scheme with neurological grade 1 representing spinal pain on
      manipulation down to neurological grade 5 representing paraplegia with no deep
      pain sensation. Results: Data were collected for 98 cats that had been caught in
      the thoracolumbar area. A total of 71 cats were included in the statistical
      analysis after excluding 27 cats for the following reasons:
      monoparesis/monoplegia by getting one limb caught only (15), no initial
      neurological examination (5), was dead on arrival (1), caught within the
      thoracolumbar area but no clinical or neurological abnormalities (6). The
      proportional mortality rate overall was 35% (25/71) with 65% of these (16/25)
      dying with clinical signs of respiratory distress. The proportional mortality
      rate of patients with a neurological grade of 5 on admission was 55% (17/31).
      Conclusions: Mortality was influenced by the severity of neurological grade on
      admission, with the majority of cats having a neurological grade of 5 (paraplegia
      with loss of deep pain perception) at admission dying (11/31) rather than
      undergoing euthanasia on admission at the owner's request (6/31). In the
      survivors' group, loss of deep pain perception was not a negative prognostic
      factor for regaining motor function although it was associated with mortality.

PMID- 29225896
TI  - Incidence of diabetes mellitus and factors associated with its development in HIV
      positive patients over the age of 50.
AB  - Objective: We sought to determine the incidence and factors associated with
      development of diabetes mellitus (DM) in older HIV-infected individuals. Research
      design and methods: We analyzed data from people living with HIV (PLWH) >=50
      years of age enrolled in a large urban HIV outpatient clinic in Vancouver,
      British Columbia. Patients were categorized as having DM if they had random blood
      sugar >=11.1 mmol/L, fasting blood sugar >=7 mmol/L, HbA1C >=6.5%, antidiabetic
      medication use during the follow-up period, or medical chart review confirming
      diagnosis of DM. We estimated the probability of developing DM, adjusting for
      demographic and clinical factors, using a logistic regression model. Results:
      Among 1065 PLWH followed for a median of 13 years (25th and 75th percentile (Q1
      Q3): 9-18), the incidence of DM was 1.61/100 person-years follow-up. In the
      analysis of factors associated with new-onset DM (n=703), 88% were male, 38% had
      a history of injection drug use, 43% were hepatitis C coinfected, and median body
      mass index was 24 kg/m2 (Q1-Q3: 21-27). Median age at antiretroviral therapy
      (ART) initiation was 48 years (Q1-Q3: 43-53) and at DM diagnosis was 55 years (Q1
      Q3: 50-61). Patients who started ART in 1997-1999 and had a longer exposure to
      older ART were at the highest risk of developing DM. Conclusions: Among PLWH aged
      >=50 years, the incidence of DM was 1.39 times higher than men in the general
      Canadian population of similar age. ART initiated in the early years of the
      epidemic and exposure to older ART appeared to be the main drivers of the
      development of DM.

PMID- 29225898
TI  - A survey of current practices and influences on the choice of suture material,
      pattern and size used in commonly performed procedures in UK small animal
      veterinary practice.
AB  - Objectives: A survey of UK veterinarians was conducted to determine factors
      influencing suture choice and current suture practice for common surgical
      procedures. Methods: An online survey was designed and the survey was sent to
      central practice emails obtained from the 2011 Royal College of Veterinary
      Surgeons (RCVS) practice database. Results: Two hundred and thirty-nine surveys
      were completed (203 with no additional postgraduate qualifications (NAQ), 16 with
      RCVS certificates and 19 with diplomas). Forty-seven per cent of veterinary
      surgeons reported they would benefit from Continued Professional Development
      (CPD) pertaining to suture material selection and techniques. The NAQ group
      ranked practice policy, colleague influence, cost of suture material and
      undergraduate teaching significantly greater than diploma and certificate
      holders. The widest differences between suture material selection, pattern and
      size were identified when comparing diploma holders and the NAQ group. Diploma
      holders tended to choose smaller sized suture material when compared with the NAQ
      group. Clinical significance: In conclusion, postgraduate qualifications have a
      significant effect on the choice, pattern and size of suture material used for
      many routine surgical procedures. Findings suggest that further postgraduate
      training pertaining to the selection and use of suture material is worthwhile and
      improved guidance of choice of suture material for commonly performed surgical
      procedures may be beneficial.

PMID- 29225899
TI  - A cluster randomized controlled trial for child and parent weight management:
      children and parents randomized to the intervention group have correlated changes
      in adiposity.
AB  - Background: Studies have suggested that obesity is linked within families and
      that successful interventions involve both the parent and child with obesity.
      However little information exists regarding similarities in adiposity and weight
      loss between the parent and child, especially in low socio-economic ethnically
      diverse households. Methods: The purpose of this study was to examine the
      relationships between the changes from baseline over time in adiposity, weight,
      health behaviors, and self-efficacy in children (n = 184) and parents (n = 184)
      participating in an 18-month weight loss program. Within the intervention group
      only and for each post-baseline time point, Pearson correlation coefficients were
      computed for children's changes (from baseline) in adiposity, weight, health
      behaviors, and self-efficacy, with their parents' corresponding changes from
      baseline, to determine how strongly the dyads were correlated. Results: At the
      completion of 18 months, the intervention group parents demonstrated strong
      positive correlations between parent and child change in waist circumference (r =
      0.409, p < 0.001), triceps (r = 0.332, p < 0.001), and subscapular (r = 0.292, p
      = 0.002) skinfolds. There were no significant correlations between weight, health
      behaviors, eating, and exercise self-efficacy. Conclusions: The results suggest
      that in the Southern United States low-income parents and their children with
      obesity are strongly correlated. Trial registration: NCT01378806 Retrospectively
      Registered on June 22, 2011.

PMID- 29225900
TI  - Decreased magnesium status may mediate the increased cardiovascular risk
      associated with calcium supplementation.

PMID- 29225901
TI  - Immediate response in markers of inflammation and angiogenesis during exercise: a
      randomised cross-over study in heart transplant recipients.
AB  - Background: The present study explored and compared the immediate responses in
      markers of inflammation and angiogenesis in maintenance heart transplant (HTx)
      recipients before, during and after sessions of high-intensity interval training
      (HIT) versus moderate-intensity continuous training (MICT). The study aimed to
      explain some of the trigger mechanisms behind HIT in HTx recipients. Methods:
      This cross-over study included 14 HTx patients (mean+/-SD age: 53+/-13 years;
      time since HTx, 3+/-2 years). All participants underwent baseline blood samples
      and a cardiopulmonary exercise test during their first visit. The next two visits
      included one HIT session and one MICT session, in randomised order. Blood samples
      were taken during and after each exercise session. Myokines and inflammatory
      markers related to vascular inflammation, blood-platelet activation and
      modulation of angiogenesis were analysed. Results: The main findings in this
      study were (1) exercise, regardless of intensity, induced a significant immediate
      response in several vascular, angiogenetic and in particular platelet-derived
      inflammatory mediators in HTx recipients. (2) HIT showed trends to induce an
      increased response in von Willebrand factor, vascular endothelial growth factor-1
      and angiopoetin-2, and a decreased response in growth differentiation factor-15,
      compared with MICT. Conclusions: This pattern and in particular the trend towards
      an increased angiogenetic mediator response could contribute to the beneficial
      effects of HIT in HTx recipients. Trial registration number: NCT02602834.

PMID- 29225902
TI  - Postprandial insulin assay as the earliest biomarker for diagnosing pre-diabetes,
      type 2 diabetes and increased cardiovascular risk.

PMID- 29225904
TI  - Late-stage left ventricular dysfunction in adult survivors of tetralogy of Fallot
      repair in childhood.
AB  - Objective: Left ventricular systolic dysfunction (LVSD) in adult survivors of
      tetralogy of Fallot (TOF) repair in childhood has been observed, although the
      relationship with long-term outcome remains inadequately described. Methods: A
      cohort of 44 consecutive adult patients with TOF repair in childhood were
      followed prospectively from January 2001 through June 2016. LVSD was defined as
      an echocardiographically derived left ventricular (LV) ejection fraction <0.55.
      Clinical and demographic characteristics in patients with and without LVSD were
      compared. Event-free survival (all-cause death or hospitalisation) was estimated
      using the product limit method. Results: The average time from childhood surgical
      repair to cohort inception was similar between groups (LVSD, 33.7+/-12.7 years;
      normal LV function, 36.1+/-14.9 years; P=0.62) as were their mean ages (LVSD,
      36.5+/-14.5 years; normal LV function, 40.7+/-15.2 years; P=0.73). Patients with
      LVSD (n=13) had more prior surgeries, more frequent history of significant
      pulmonic regurgitation, right ventricular systolic dysfunction and more
      implantable cardiac devices. Over a total observation time of 15.5 years,
      patients with LVSD were at significantly higher risk of all-cause death or
      hospitalisation (P=0.006). Onset of LVSD frequently preceded an adverse outcome.
      Conclusions: In this cohort of adult patients with TOF repair in childhood
      followed for a total of 550 patient-years, the frequency of LVSD was 30%. LVSD
      was associated with lower event-free survival. The appearance of LVSD many years
      after TOF repair may herald the onset of an adverse outcome.

PMID- 29225903
TI  - Early clinical outcomes as a function of use of newer oral P2Y12 inhibitors
      versus clopidogrel in the EUROMAX trial.
AB  - Objective: To ascertain whether different oral P2Y12 inhibitors might affect
      rates of acute stent thrombosis and 30-day outcomes after primary percutaneous
      coronary intervention (pPCI). Methods: The European Ambulance Acute Coronary
      Syndrome Angiography (EUROMAX) randomised trial compared prehospital bivalirudin
      with heparin with optional glycoprotein IIb/IIIa inhibitor treatment in patients
      with ST-segment elevation myocardial infarction triaged to pPCI. Choice of P2Y12
      inhibitor was at the investigator's discretion. In a prespecified analysis, we
      compared event rates with clopidogrel and newer oral P2Y12 inhibitors (prasugrel,
      ticagrelor). Rates of the primary outcome (acute stent thrombosis) were examined
      as a function of the P2Y12 inhibitor used for loading and 30-day outcomes
      (including major adverse cardiac events) as a function of the P2Y12 inhibitor
      used for maintenance therapy. Logistic regression was used to adjust for
      differences in baseline characteristics. Results: Prasugrel or ticagrelor was
      given as the loading P2Y12 inhibitor in 49% of 2198 patients and as a maintenance
      therapy in 59%. No differences were observed in rates of acute stent thrombosis
      for clopidogrel versus newer P2Y12 inhibitors (adjusted OR 0.50, 95% CI 0.13 to
      1.85). After adjustment, no difference was observed in 30-day outcomes according
      to maintenance therapy except for protocol major (p=0.029) or minor (p=0.025)
      bleeding and Thrombolysis In Myocardial Infarction minor bleeding (p=0.002),
      which were less frequent in patients on clopidogrel. Consistent results were
      observed in the bivalirudin and heparin arms. Conclusions: The choice of
      prasugrel or ticagrelor over clopidogrel was not associated with differences in
      acute stent thrombosis or 30-day ischaemic outcomes after pPCI. Trial
      registration number: NCT01087723.

PMID- 29225905
TI  - Added sugars drive coronary heart disease via insulin resistance and
      hyperinsulinaemia: a new paradigm.

PMID- 29225907
TI  - Changes in the gut microbiota composition and the plasma ghrelin level in
      patients with Helicobacter pylori-infected patients with eradication therapy.
AB  - Objective: To investigate the influence of antimicrobials on both the gut
      microbiota structure and the plasma ghrelin level using Helicobacter pylori
      infected patients who underwent eradication therapy. Design: Twenty H. pylori
      infected patients (mean age 68.3 years old) who underwent eradication therapy
      participated in the study. For the therapy, patients had 1 week of triple therapy
      consisting of amoxicillin, clarithromycin and proton-pump inhibitors. Stool and
      blood samples were obtained before (S1), immediately after (S2) and/or 3 months
      after (S3) the therapies. The concentrations of ghrelin and leptin in the blood
      were assayed using an ELISA. The V3-V4 region of the 16S rRNA gene was amplified
      using bacterial DNA from the stool, and about 50 000 high-quality amplicons per
      sample were grouped into operational taxonomic units for bacteriological
      analyses. Results: The Bacteroidetes:Firmicutes (B:F) ratio was significantly
      greater at S3 than S1 (P<0.01). This increase in the B:F ratio between S3 and S1
      was found in 15 out of 20 patients. A significant decrease in the concentration
      of active ghrelin (P=0.003) in the plasma was observed between S3 and S1. There
      was a statistically significant correlation between the rate of patients whose
      B:F ratio increased and that of patients whose active ghrelin level decreased
      between S3 and S1 according to Fisher's exact probability test (P=0.03).
      Conclusions: Changes in the gut microbiota, such as the B:F ratio after treatment
      with antimicrobials, might cause a change in the plasma ghrelin level, as the
      direct and earliest target of antimicrobials would be the microbiota rather than
      the hormone-secreting system.

PMID- 29225906
TI  - Patient Engagement in Kidney Research: Opportunities and Challenges Ahead.
AB  - Purpose of Review: Patient engagement in research is increasingly recognized as
      an important component of the research process and may facilitate translation of
      research findings. To heighten awareness on this important topic, this review
      presents opportunities and challenges of patient engagement in research, drawing
      on specific examples from 4 areas of Canadian kidney research conducted by New
      Investigators in the Kidney Research Scientist Core Education and National
      Training (KRESCENT) Program. Sources of Information: Research expertise,
      published reports, peer-reviewed articles, and research funding body websites.
      Methods: In this review, the definition, purpose, and potential benefits of
      patient engagement in research are discussed. Approaches toward patient
      engagement that may help with translation and uptake of research findings into
      clinical practice are highlighted. Opportunities and challenges of patient
      engagement are presented in both basic science and clinical research with the
      following examples of kidney research: (1) precision care in focal and segmental
      glomerulosclerosis, (2) systems biology approaches to improve management of
      chronic kidney disease and enhance kidney graft survival, (3) reducing the
      incidence of suboptimal dialysis initiation, and (4) use of patient-reported
      outcome measures (PROMs) and patient-reported experience measures (PREMs) in
      kidney practice. Key Findings: Clinical research affords more obvious
      opportunities for patient engagement. The most obvious step at which to engage
      patients is in the setting of research priorities. Engagement at all stages of
      the research cycle may prove to be more challenging, and requires a detailed
      plan, along with funds and infrastructure to ensure that it is not merely
      tokenistic. Basic science research is several steps removed from the clinical
      application and involves complex scientific concepts, which makes patient
      engagement inherently more difficult. Limitations: This is a narrative review of
      the literature that has been partly influenced by the perspectives and
      experiences of the authors and focuses on research conducted by the authors. The
      evidence base to support the suggested benefits of patient engagement in research
      is currently limited. Implications: The formal incorporation of patients'
      priorities, perspectives, and experiences is now recognized as a key component of
      the research process. If patients and researchers are able to effectively work
      together, this could enhance research quality and efficiency. To effectively
      engage patients, proper infrastructure and dedicated funding are needed. Going
      forward, a rigorous evaluation of patient engagement strategies and their
      effectiveness will be needed.

PMID- 29225908
TI  - An unusual presentation of tyrosine hydroxylase deficiency.
AB  - Background: Dopa-responsive dystonia (DRD) has largely been associated with
      autosomal dominant mutations in the GCH1 gene leading to GTP cyclohydrolase 1
      deficiency. More recently, a deficiency in tyrosine hydroxylase (TH) has been
      recognized to cause DRD. This is a rare disorder resulting from genetic mutations
      in the TH gene on chromosome 11. The phenotype ranges from DRD with complete
      resolution on levodopa to infantile parkinsonism and encephalopathy only
      partially responsive to levodopa. Here we discuss an adult with TH deficiency
      with a history of possible parkinsonism and dystonia responsive to levodopa,
      notable for a residual dynamic segmental dystonia. Case presentation: Our patient
      grew up in rural Myanmar with limited medical care. Childhood was normal except
      for episodic illness with difficulty moving and speaking. At 18 years he
      developed difficulty writing. At 21 years he could not speak, walk, or write and
      was taken to a city hospital. Multiple medications were tried without benefit
      until he received carbidopa/levodopa, to which he had a miraculous response.
      Since then he has attempted to come off medication, however after several weeks
      his symptoms returned. On presentation to us at 31 years he was taking 450 mg
      levodopa/day and 4 mg trihexyphenidyl/day. He had a dynamic dystonia in his neck
      and trunk, subtle at rest and prominent with walking. He exhibited a sensory
      trick when touching his hand to his chin; improvement occurred to a lesser degree
      when he imagined touching his chin, and to an even lesser degree when the
      examiner touched his chin. He had no parkinsonism. He underwent genetic testing
      which revealed a homozygous variant mutation in the TH gene (p.Thr494Met) leading
      to a diagnosis of autosomal recessive tyrosine hydroxylase deficiency.
      Conclusions: TH deficiency can cause a broad range of clinical symptoms and
      severity. As more cases are discovered, the phenotype expands. Here we describe a
      unique case of DRD and possible parkinsonism due to TH deficiency with residual
      symptoms of dystonia that was task dependent and responded to a sensory trick. In
      addition, while the history is limited, it is possible he may have had episodes
      similar to "lethargy-irritability crises" seen in more severe cases. In large
      part he fits within the milder form of TH hydroxylase deficiency.

PMID- 29225909
TI  - Improved treatment satisfaction and medication adherence after readjusting oral
      medication regimens with the cooperation of health insurance pharmacy in type 2
      diabetic patients in Japan.
AB  - Background: Treatment satisfaction and medication adherence can be improved if
      physicians carefully monitor the situations, check the level of difficulties
      patients experience when taking medications at specific times, and readjust
      medication regimens based on this information. However, physicians in Japan
      encounter difficulties in taking enough time to collect this information in
      clinical practice. The aim of the current study was to investigate improvements
      in satisfaction and adherence with the cooperation of a health insurance pharmacy
      in clinical practice. Methods: We retrospectively analyzed 29 type 2 diabetic
      outpatients who were receiving their prescriptions at a medical clinic and
      filling prescriptions at a nearby pharmacy. The pharmacy collected information
      regarding satisfaction, adherence, and preferred time of taking medications, and
      provided these data to the clinic. The oral medication regimens for these 29
      patients were readjusted based on the information obtained. Results: After
      readjustments, the dosing frequency was decreased from 3.4 +/- 1.2 to 1.8 +/- 0.5
      times/day, and the number of pills was reduced from 5.7 +/- 2.0 to 4.5 +/- 1.7
      (both p < 0.001). Increases in treatment satisfaction from 33 +/- 12 to 44 +/- 10
      points (n = 29, p < 0.001) were observed when assessed using a questionnaire (60
      point maximum). Medication adherence based on pill counts increased from 75% +/-
      22% to 91% +/- 14% (n = 24, p < 0.001) (5 patients were excluded due to missing
      data). Conclusions: Treatment satisfaction and medication adherence were improved
      after readjustments of oral medication regimens with the cooperation of a health
      insurance pharmacy in clinical practice in Japan.

PMID- 29225910
TI  - Reduced susceptibility to fluconazole in a cat with histoplasmosis.
AB  - Case summary: An 11-year-old neutered male domestic longhair cat was diagnosed
      with histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph
      node size initially decreased with fluconazole therapy (11.8 mg/kg PO q12h);
      however, after 13 months of continuous fluconazole therapy, lymphadenomegaly
      worsened and samples were collected for culture and antifungal susceptibility.
      The Histoplasma capsulatum isolate had a very high fluconazole minimum inhibitory
      concentration (MIC) of 64 ug/ml and an itraconazole MIC of 0.06 ug/ml. The owner
      declined a change to itraconazole and, ultimately, the cat developed neurologic
      signs and was euthanized. Owing to the initial response to fluconazole followed
      by treatment failure and high MIC value, acquired fluconazole resistance was
      suspected. Clinical breakpoints for fluconazole for the dimorphic fungi are not
      available to define true antifungal resistance. Relevance and novel information:
      This is the first published report of reduced susceptibility to fluconazole in a
      cat being treated for histoplasmosis. Fluconazole failure and increases in MIC
      between pretreatment and long-term treatment isolates are known to occur in
      humans with histoplasmosis. Practitioners should be aware of this possibility
      when treating cats with fluconazole (particularly in cases with long-term [>1
      year] fluconazole therapy or in cases with disease recrudescence).

PMID- 29225911
TI  - Understanding muscle-immune interactions in adolescent idiopathic scoliosis: a
      feasibility study.
AB  - Background: Adolescent idiopathic scoliosis (AIS) is the most common form of
      scoliosis in children, and its cause remains unknown. The Immune-metabolic
      CONnections to Scoliosis (ICONS) Study was designed to elucidate the potential
      mechanisms by which immune system-paraspinal muscle crosstalk contributes to the
      development of AIS. In this report, we document the evaluation of ICONS Study
      feasibility. Methods: This study was conducted at a tertiary pediatric academic
      center in Hamilton, Ontario, Canada. We included boys and girls, aged 10-17 years
      with a diagnosis of AIS requiring corrective spinal surgery. Exclusion criteria
      included patients on high-dose steroids, immunosuppressive therapy, anti
      thrombotic medications, those with an active infection for 15 days before
      participation, autoimmune disease, pregnancy, and patients who were unwilling to
      consent.Pre-determined feasibility criteria included permission to approach
      participants and recruitment rates of 80%, consenting of at least 80% of
      participants to provide biological samples, 90% or higher case report form and
      questionnaire completion, resources to be sufficient in at least 80% of
      recruitments, and the ability to successfully collect and process 80% or more of
      the biological samples needed for this study. Results: Between August 2013 and
      October 2014, we identified 32 potential participants with AIS, but had the
      resources to approach only 16, of which 12 (75%) agreed to be approached by the
      research team, and all consented to participate. Of the 12 participants
      recruited, 11 questionnaire packages and muscle biopsies (91.7% for each
      objective) were collected, while other biological samples (serum, plasma, whole
      blood for DNA and RNA processing, urine) were collected from all participants.
      Conclusions: The ICONS study protocols and procedures are feasible. However,
      recruitment rates were less than predicted. For the full study, we plan on
      prolonging the recruitment phase and the inclusion of additional centers to
      achieve recruitment targets.

PMID- 29225912
TI  - Effects of virtual rehabilitation versus conventional physical therapy on
      postural control, gait, and cognition of patients with Parkinson's disease: study
      protocol for a randomized controlled feasibility trial.
AB  - Background: There is an association among postural instability, gait dysfunction,
      and cognitive impairment in subjects with Parkinson's disease (PD). Difficulty in
      dividing attention, response inhibition, and visuospatial attention deficiencies
      may contribute to the impairment of motor performance during daily activities.
      There are strong evidences that physical therapy can prevent physical and
      cognitive decline in individuals with PD. Recently, the European Physiotherapy
      Guideline (EPG) was developed based on randomized clinical trials about the
      effectiveness of the physical therapy to improve the functional deficiencies of
      individuals with PD. The EPG did not include the use of promising new
      intervention as virtual reality in PD due the lack of studies about its safety,
      feasibility and effectiveness. Therefore, this study protocol had as objective to
      evaluate the feasibility, safety and effectiveness of a physical therapy program
      based on the European Physiotherapy Guideline (EPG) compared to Kinect-based
      training on postural control, gait, cognition, and quality of life (QoL) of
      Individuals with PD. Methods/design: A single-blind, parallel, randomized,
      controlled feasibility trial will be conducted with a sample of 32 individuals
      diagnosed with idiopathic PD. Participants will be allocated into control group
      (CG) and experimental group (EG). The intervention of the CG will be conventional
      physical therapy, and the intervention of the EG will be a supervised practice of
      five Kinect games. Both groups will perform 14 sessions of 1 h each one, twice a
      week over 7 weeks. Process outcomes will be safety, feasibility, adherence, and
      acceptability. Safety will be assessed by the proportion of participants who
      experienced intervention-related adverse events or any serious adverse event
      during the study period. Feasibility will be assessed through the scores of the
      games recorded in all training sessions. Adherence will be assessed through the
      participant's attendance. Acceptability will be the motivation of the
      participants regarding the interventions. Clinical outcomes will be (1) postural
      control, (2) cognitive function, (3) balance, (4) gait, and (5) QoL. Individuals
      will be assessed pre- and post-interventions and after 30 days by a blinded
      evaluator. Discussion: This protocol will clarify if an intervention based on
      Kinect games will be feasible, safe, and acceptable for individuals with PD
      compared to conventional physical therapy. We will verify whether the proposed
      interventions can improve clinical outcomes as postural control, gait, cognition,
      and QoL of individuals with PD. Our hypothesis is that both Kinect games and
      conventional physical therapy will be feasible, safe, and acceptable for
      individuals with PD and will promote positive clinical effects. The results of
      this feasibility study will be used to design a future definitive clinical trial.
      Trial registration: Unique identification number in WHO Trial Registration: U1111
      1171-0371. Brazilian Clinical Trial Registration Number RBR-27kqv5, registration
      date: February, 2016.

PMID- 29225913
TI  - Action 3:30R: protocol for a cluster randomised feasibility study of a revised
      teaching assistant-led extracurricular physical activity intervention for 8- to
      10-year-olds.
AB  - Background: Approximately half of 7-year-old children do not meet physical
      activity (PA) recommendations. Interventions targeting primary school children's
      afterschool discretionary time could increase PA. Teaching assistants (TAs) are a
      school resource and could be trained to deliver after-school PA programmes.
      Building on earlier work, this paper describes the protocol for a cluster
      randomised feasibility study of a teaching assistant-led after-school
      intervention aimed at increasing PA levels of year 4 and 5 children (8-10 years
      old). Methods: Phase 1-pre-baseline: 12 schools will be recruited. In all
      schools, self-reported PA will be measured in all consenting year 3 and 4
      children. In four schools, pupils will additionally wear a waist-worn Actigraph
      accelerometer for 7 days.Phase 2-baseline: schools will be randomised to one of
      two enhanced recruitment strategies being tested for children: (1) a club
      briefing and (2) the briefing plus a taster Action 3:30 session. Up to 30
      children per school will be able to attend Action 3:30 sessions and will provide
      baseline data on height, weight, psychosocial variables and accelerometer
      measured PA.Phase 3-intervention and follow-up: Schools randomised into
      intervention or control arm. Intervention schools (n = 6) will receive a 15-week
      after-school programme when children are in years 4 and 5, run by TAs who have
      attended a 25-h Action 3:30 training programme. Control schools (n = 6) will
      continue with normal practice. Follow-up measures will be a repeat of baseline
      measures at the end of the 15-week intervention.Phase 4-process evaluation:
      session attendance, perceived enjoyment and perceived exertion will be assessed
      during the intervention, as well as the economic impact on schools. Post-study
      qualitative assessments with TAs, school contacts and pupils will identify how
      the programme could be refined. Accelerometer-determined minutes of moderate-to
      vigorous physical activity (MVPA) per day will be calculated as this is likely to
      be the primary outcome in a future definitive trial. Discussion: The Action 3:30
      cluster randomised feasibility trial will assess the public health potential of
      this intervention approach and provide the information necessary to progress to a
      definitive cluster randomised controlled trial. Trial registration:
      ISRCTN34001941. Registered 01/12/2016.

PMID- 29225914
TI  - Status of hypertension screening in the Korea National General Health Screening
      Program: a questionnaire survey on 210 screening centers in two metropolitan
      areas.
AB  - Background: The purpose of this survey was to evaluate the performance of
      hypertension screening in medical institutions conducting the national general
      health screening program of the Republic of Korea. Methods: We contacted 700
      medical institutions of Seoul and Incheon areas which performed the national
      general health screening program in 2016, and 210 of them completed telephone
      survey. The questions asked in the survey include equipment, environment,
      personnel and quality control procedures for blood pressure (BP) measurement, and
      interpretation of the measurements. Results: A majority of the responding
      screening centers used oscilloscope sphygmomanometers (51.9%), had only one-sized
      cuff (65.2%), and measured BP in open space (54.3%). BP levels were measured
      mainly by nurses (62.0%) and doctors (25.0%), after a 1 to10 minutes (84.9%) of
      resting period. A 75.2% of screening centers regularly calibrated
      sphygmomanometers, 81.4% had a manual for BP measurement, and 59.0% had a
      training program. A 80.0% of respondents answered that they used averages of
      multiple BP measurements to determine an individual's BP level, and 82.9%
      answered that criteria for hypertension was systolic BP >=140 mmHg and/or
      diastolic BP >= 90 mmHg. If a screening finds an individual with hypertension,
      82.9% of centers recommend revisiting for a second BP measurement rather than
      start medication immediately. Conclusion: In most medical institutions performing
      general health screening program, certified medical personnel measure BP and
      interpret the results according to established protocols. However, there is room
      for improvement in the equipment, environment and quality control procedures for
      BP measurement.

PMID- 29225915
TI  - MDHAQ/RAPID3 scores in patients with osteoarthritis are similar to or higher than
      in patients with rheumatoid arthritis: a cross-sectional study from current
      routine rheumatology care at four sites.
AB  - Objective: To compare patients with a primary diagnosis of osteoarthritis (OA)
      versus rheumatoid arthritis (RA) for scores on a patient self-report MDHAQ/RAPID3
      (Multidimensional Health Assessment Questionnaire/Routine Assessment of Patient
      Index Data 3), and for physician global assessment (DOCGL). Methods: All patients
      with all diagnoses complete an MDHAQ/RAPID3 at all routine rheumatology visits in
      the waiting area before seeing a rheumatologist at four sites, one in Australia
      and three in the USA. The two-page MDHAQ includes 0-10 scores for physical
      function (in 10 activities), pain and patient global assessment [on 0-10 visual
      analogue scales (VAS)], compiled into a 0-30 RAPID3, as well as fatigue and self
      report painful joint count scales. Rheumatologists estimate a 0-10 DOCGL VAS.
      Demographic, MDHAQ/RAPID3 and DOCGL data from a random visit were compared in
      patients with RA versus patients with OA using multivariate analysis of variance,
      adjusted for age, disease duration and formal education level. Results: Median
      RAPID3 was higher in OA versus RA at all four sites (11.7-16.8 vs 6.2-11.8)
      (p<0.001 at three sites). Median DOCGL in OA versus RA was 5 vs 4, 4 vs 3.7, 2.2
      vs 2.5 and 2 vs 1. Patterns were similar for individual RAPID3 items, fatigue and
      painful joint scales, and in stratified analyses of patients aged 55-70.
      Conclusion: Patient MDHAQ/RAPID3 and physician DOCGL indicate similar or higher
      disease burden in OA versus RA. Routine MDHAQ/RAPID3 allows direct comparisons of
      the two diseases. The findings suggest possible revision of current clinical and
      public policy views concerning OA.

PMID- 29225916
TI  - Prediction and benefits of minimal disease activity in patients with psoriatic
      arthritis and active skin disease in the ADEPT trial.
AB  - Objectives: To determine the proportion of patients with psoriatic arthritis in
      the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal
      disease activity (MDA) and its individual components at 1 or more visits over 144
      weeks, identify baseline predictors of MDA achievement, and evaluate the
      association of MDA status with independent quality of life (QoL)-related patient
      reported outcomes (PROs). Methods: Univariate and multivariate analyses were used
      to identify the baseline characteristics that predicted achievement of MDA at
      individual time points (weeks 12 through 144) or sustained MDA (achievement of
      MDA at 2 consecutive time points 12 weeks apart). The association of independent
      QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results:
      In univariate analyses, higher baseline patient assessment of pain, tender joint
      count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ
      DI) score were significantly associated with lower likelihood of achieving MDA at
      later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a
      significant predictor for failure to achieve MDA at later time points.
      Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI
      score. Achievement of different MDA components appeared to be treatment
      dependent. MDA achievers had significantly better QoL-related PROs and greater
      improvements in PROs from baseline to week 24 compared with non-achievers.
      Conclusions: Higher HAQ-DI score was the most consistent baseline factor that
      decreased the likelihood of achieving MDA and sustained MDA at later time points.
      Achieving MDA was associated with better independent QoL-related PROs.

PMID- 29225917
TI  - Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative
      lupus nephritis and non-responsiveness to immunosuppressive therapy.
AB  - Introduction: P-glycoprotein (P-gp) expression on activated lymphocytes in
      systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular
      drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in
      the pathogenesis of SLE remains unclear. The aim of this study was to determine
      the importance of P-gp+CD4+ cells in organ manifestations in refractory SLE.
      Methods: The proportion of P-gp+CD4+ cells was determined by flow cytometry in
      peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal
      biopsy specimens were examined by immunohistochemistry for P-gp expression.
      Results: CD69 is a marker of CD4 cell activation. The proportion of both P-gp
      expressing CD4+ cells and CD69-expressing CD4+ cells in peripheral blood was
      higher in SLE than control. The proportion of P-gp+CD69+CD4+ cells correlated
      with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor
      responders to corticosteroids. Furthermore, the proportion of P-gp+CD69+CD4+
      cells was significantly higher in proliferative lupus nephritis (LN) with poor
      response to corticosteroids. The efficacy of immunosuppressive therapy depended
      on the regulation of the proportion of P-gp+CD69+CD4+ cells. Marked accumulation
      of P-gp+CD4+ cells in renal interstitial tissue and high proportion of peripheral
      P-gp+CD69+CD4+ cells were noted in patients with proliferative LN. Conclusions:
      The results showed high proportion of P-gp+CD69+CD4+ cells in peripheral blood
      and their accumulation in renal tissue in patients with proliferative LN
      refractory to CS therapy, suggesting that P-gp expression on activated CD4+ T
      cells is a potentially useful marker for refractoriness to treatment and a novel
      target for treatment.

PMID- 29225918
TI  - Correction: Efficacy and safety of non-pharmacological and non-biological
      pharmacological treatment: a systematic literature review informing the 2016
      update of the ASAS/EULAR recommendations for the management of axial
      spondyloarthritis.
AB  - [This corrects the article DOI: 10.1136/rmdopen-2016-000397.][This corrects the
      article DOI: 10.1136/rmdopen-2016-000397.].

PMID- 29225919
TI  - Multiple common and rare variants of ABCG2 cause gout.
AB  - Objective: Previous studies have suggested an association between gout
      susceptibility and common dysfunctional variants in ATP-binding cassette
      transporter subfamily G member 2/breast cancer resistance protein (ABCG2/BCRP),
      including rs72552713 (Q126X) and rs2231142 (Q141K). However, the association of
      rare ABCG2 variants with gout is unknown. Therefore, we investigated the effects
      of rare ABCG2 variants on gout susceptibility in this study. Methods: We
      sequenced the exons of ABCG2 in 480 patients with gout and 480 healthy controls
      (Japanese males). We also performed functional analyses of non-synonymous
      variants of ABCG2 and analysed the correlation between urate transport function
      and scores from the protein prediction algorithms (Sorting Intolerant from
      Tolerant (SIFT) and Polymorphism Phenotyping v2 (PolyPhen-2)). Stratified
      association analyses and multivariate logistic regression analysis were performed
      to evaluate the effects of rare and common ABCG2 variants on gout susceptibility.
      Results: We identified 3 common and 19 rare non-synonymous variants of ABCG2.
      SIFT scores were significantly correlated with the urate transport function,
      although some ABCG2 variants showed inconsistent scores. When the effects of
      common variants were removed by stratified association analysis, the rare
      variants of ABCG2 were associated with a significantly increased risk of gout
      (OR=3.2, p=6.4*10-3). Multivariate logistic regression analysis revealed that the
      size effect of these rare ABCG2 variants (OR=2.7, p=3.0*10-3) was similar to that
      of the common variants, Q126X (OR=3.4, p=3.2*10-6) and Q141K (OR=2.3, p=2.7*10
      16). Conclusions: This study revealed that multiple common and rare variants of
      ABCG2 are independently associated with gout. These results could support both
      the 'Common Disease, Common Variant' and 'Common Disease, Multiple Rare Variant'
      hypotheses for the association between ABCG2 and gout susceptibility.

PMID- 29225920
TI  - Relationship between shift work and the onset of rheumatoid arthritis.
AB  - Background: Environmental factors play a prominent role in rheumatoid arthritis
      (RA) aetiology. Shift work has previously been associated with increased RA risk
      in females. The aim of this study was to investigate the potential association,
      including a dose-response association, between permanent night shift work,
      rotating shift work and day-oriented shift work and risk of developing
      anticitrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA.
      Methods: The present report is based on a population-based, case-control study
      with incident cases of RA (1951 cases and 2225 controls matched by age, gender
      and residential area). Using logistic regression, occurrence of RA among subjects
      who have been exposed to different kinds of shift work was compared with that
      among those who have never been exposed by calculating the OR with a 95% CI.
      Results: Rotating shift work and day-oriented shift work increased the risk of
      developing ACPA-positive RA (OR 1.3, 95% CI 1.0 to 1.7 and OR 1.3, 95% CI 1.0 to
      1.6), but not ACPA-negative RA. Permanent night shift work appeared to be a
      protective factor both against ACPA-positive RA (OR 0.7, 95% CI 0.6 to 0.9) and
      ACPA-negative RA (OR 0.8, 95% CI 0.6 to 1.0). For both subsets of RA, significant
      trends showed a lower risk of developing RA with increasing duration of permanent
      night shift work (p value for trend 0.002 vs 0.04). Conclusions: Sleep
      restriction as a consequence of shift work is associated with several biological
      effects among which changes in melatonin production may be involved. The present
      epidemiological findings of a complex relationship between sleep patterns and
      different forms of RA may be of importance for increasing the understanding of
      the pathophysiology of RA.

PMID- 29225921
TI  - Geo-epidemiology of temporal artery biopsy-positive giant cell arteritis in
      Australia and New Zealand: is there a seasonal influence?
AB  - Objective: Previous studies, although inconclusive, have suggested possible
      associations of environmental risk factors with the development of giant cell
      arteritis (GCA). We aim to investigate seasonal influence on the incidence of GCA
      across Australia and New Zealand. Methods: In establishing an international study
      to investigate the molecular aetiology of GCA, archived temporal artery biopsy
      (TAB) specimens primarily from Australia and New Zealand were obtained.
      Demographic details including age, sex and date of TAB were collected from
      collaborating pathology departments. The season in which GCA was diagnosed was
      determined and compared with previous reports investigating the association
      between environmental risk factors and GCA. Results: Our study comprises data
      from 2224 TAB-positive patients with GCA; 2099 of which were from patients in
      Australia and New Zealand. The mean age at time of diagnosis was 76.4 years of
      age. The female-to-male ratio was 2.2:1. We noted equal distribution of the
      incidence rate across all four seasons (530-580 cases diagnosed every quarter).
      Statistical analysis of seasonal variation by Poisson regression and cosinor
      methods showed no incidence preponderance across seasons. Our results do not
      support a seasonal component contributing to the onset of disease. Our literature
      search identifies no consistent environmental risk factor in association with
      GCA. Conclusion: This is the largest GCA data set reported outside of Europe. Our
      results demonstrate equal distribution of the incidence rate across all four
      seasons. In contrast to some earlier reports, we did not identify evidence of a
      seasonal component contributing to the onset of disease.

PMID- 29225922
TI  - Using Participatory Learning & Action (PLA) research techniques for inter
      stakeholder dialogue in primary healthcare: an analysis of stakeholders'
      experiences.
AB  - Plain English summary: It is important for health care workers to know the needs
      and expectations of their patients. Therefore, service users have to be involved
      in research. To achieve a meaningful dialogue between service users, healthcare
      workers and researchers, participatory methods are needed. This paper describes
      how the application of a specific participatory methodology, Participatory
      Learning and Action (PLA) can lead to such a meaningful dialogue. In PLA all
      stakeholders are regarded as equal partners and collaborators in research.During
      2011-2015, a European project called RESTORE used PLA in Austria, Greece,
      Ireland, The Netherlands and the UK to investigate how communication between
      primary health care workers and their migrant patients could be improved.Seventy
      eight migrants, interpreters, doctors, nurses and other key stakeholders (see
      Table 2) participated in 62 PLA sessions. These dialogues (involving discussions,
      activities, PLA techniques and evaluations) were generally 2-3 h long and were
      recorded and analysed by the researchers.Participants reported many positive
      experiences about their dialogues with other stakeholders. There was a positive,
      trusting atmosphere in which all stakeholders could express their views despite
      differences in social power. This made for better understanding within and across
      stakeholder groups. For instance a doctor changed her view on the use of
      interpreters after a migrant explained why this was important. Negative
      experiences were rare: some doctors and healthcare workers thought the PLA
      sessions took a lot of time; and despite the good dialogue, there was
      disappointment that very few migrants used the new interpreting service.
      Abstract: Background In order to be effective, primary healthcare must understand
      the health needs, values and expectations of the population it serves. Recent
      research has shown that the involvement of service users and other stakeholders
      and gathering information on their perspectives can contribute positively to many
      aspects of primary healthcare. Participatory methodologies have the potential to
      support engagement and dialogue between stakeholders from academic, migrant
      community and health service settings. This paper focuses on a specific
      participatory research methodology, Participatory Learning and Action (PLA) in
      which all stakeholders are regarded as equal partners and collaborators in
      research.Our research question for this paper was: "Does the application of PLA
      lead to meaningful engagement of all stakeholders, and if so, what elements
      contribute to a positive and productive inter-stakeholder dialogue?". Methods We
      explored the use of PLA in RESTORE, a European FP7-funded project, during 2011
      2015 in 5 countries: Austria, Greece, Ireland, the Netherlands and the UK. The
      objective of RESTORE was to investigate and support the implementation of
      guidelines and training initiatives (G/TIs) to enhance communication in cross
      cultural primary care consultations with migrants.Seventy eight stakeholders
      (migrants, interpreters, doctors, nurses and others - see Table 2) participated
      in a total of 62 PLA sessions (discussions, activities, evaluations) of
      approximately 2-3 h' duration across the five sites. During the fieldwork,
      qualitative data were generated about stakeholders' experiences of engagement in
      this dialogue, by means of various methods including participatory evaluations,
      researchers' fieldwork reports and researcher interviews. These were analysed
      following the principles of thematic analysis. Results Stakeholders involved in
      PLA inter-stakeholder dialogues reported a wide range of positive experiences of
      engagement, and very few negative experiences. A positive atmosphere during early
      research sessions helped to create a sense of safety and trust. This enabled
      stakeholders from very different backgrounds, with different social status and
      power, to offer their perspectives in a way that led to enhanced learning in the
      group - they learned with and from each other. This fostered shifts in
      understanding - for example, a doctor changed her view on interpreted
      consultations because of the input of the migrant service-users. Conclusion PLA
      successfully promoted stakeholder involvement in meaningful and productive inter
      stakeholder dialogues. This makes it an attractive approach to enhance the
      further development of health research partnerships to advance primary
      healthcare.

PMID- 29225923
TI  - Experimental adaptation of human echovirus 11 to ultraviolet radiation leads to
      resistance to disinfection and ribavirin.
AB  - Ultraviolet light in the UVC range is a commonly used disinfectant to control
      viruses in clinical settings and water treatment. However, it is currently
      unknown whether human viral pathogens may develop resistance to such stressor.
      Here, we investigate the adaptation of an enteric pathogen, human echovirus 11,
      to disinfection by UVC, and characterized the underlying phenotypic and genotypic
      changes. Repeated exposure to UVC lead to a reduction in the UVC inactivation
      rate of approximately 15 per cent compared to that of the wild-type and the
      control populations. Time-series next-generation sequencing data revealed that
      this adaptation to UVC was accompanied by a decrease in the virus mutation rate.
      The inactivation efficiency of UVC was additionally compromised by a shift from
      first-order to biphasic inactivation kinetics, a form of 'viral persistence'
      present in the UVC resistant and control populations. Importantly, populations
      with biphasic inactivation kinetics also exhibited resistance to ribavirin, an
      antiviral drug that, as UVC, interferes with the viral replication. Overall, the
      ability of echovirus 11 to adapt to UVC is limited, but it may have relevant
      consequences for disinfection in clinical settings and water treatment plants.

PMID- 29225924
TI  - CT Dental Artifact: Comparison of an Iterative Metal Artifact Reduction Technique
      with Weighted Filtered Back-Projection.
AB  - Background: Dental hardware produces streak artifacts on computed tomography (CT)
      images reconstructed with the standard weighted filtered back projection (wFBP)
      method. Purpose: To perform a preliminary evaluation of an iterative metal
      artifact reduction (IMAR) technique to assess its ability to improve anatomic
      visualization over wFBP in patients with dental amalgam or other hardware.
      Material and Methods: CT images from patients with dental hardware were
      reconstructed using wFBP and IMAR software and soft-tissue or bone window/level
      settings. The anatomy most affected by metal artifacts was identified. Two
      neuroradiologists determined subjective and objective imaging features, including
      overall metal artifact score (1 = severe artifacts, 5 = no artifacts), soft
      tissue visualization score of the most-compromised structure, and artifact length
      along the skin surface. CT numbers were used to quantify artifact severity.
      Results: Twenty-four patients were included. IMAR improved overall metal artifact
      score in 18/24 cases (median =2 +/- 0.9 vs. 1 +/- 0.6, P < 0.001). Mean CT number
      in the most-affected anatomical structure significantly improved with IMAR (94.6
      vs. 219 HU, P = 0.002) and length of affected skin surface decreased (40.4 mm vs.
      118.7 mm, P < 0.001). However, osseous/dental artifactual defects were found in
      22/24 cases with IMAR vs. 11/24 with wFBP. Conclusion: IMAR software reduced
      metal artifact both subjectively and objectively and improved visualization of
      adjacent soft tissues. However, it produced a higher rate of artifactual defects
      in the teeth and bones than wFBP. Our findings support the use of IMAR as a
      valuable complement to, but not a replacement for, standard wFBP image
      reconstruction.

PMID- 29225925
TI  - Metal drugs become targeted.

PMID- 29225926
TI  - Does expanding primary healthcare improve hospital efficiency? Evidence from a
      panel analysis of avoidable hospitalisations in 5506 municipalities in Brazil,
      2000-2014.
AB  - Background: Hospitals account for the major share of health expenditure. Primary
      healthcare may improve efficiency at the hospital level by reducing avoidable
      admissions. We examined whether rapid expansion of primary healthcare in the
      context of Brazil's Family Health Strategy (FHS) was associated with a reduction
      in avoidable hospitalisations. Methods: We constructed panel data for 5506
      municipalities over 2000-2014. Our primary outcome was the rate of avoidable
      hospitalisations, defined with reference to the official list of ambulatory care
      sensitive conditions (ACSC). The exposure variable was FHS coverage. We used
      first-difference models at the municipality level, controlling for municipality
      characteristics and confounding trends. We ran similar models for each of the 19
      diseases in the list of ACSCs. Findings: FHS coverage expanded from 14% to 64% of
      the population between 2000 and 2014. Over the same period, the rate of avoidable
      hospitalisations fell from 17 to 10 per 1000 population. Results from the
      econometric analysis show that the FHS at full coverage was associated with an
      increase of 0.6 (95% CI 0.3 to 0.9; p<0.001) in the rate of avoidable hospital
      admissions. Expansion of the FHS was associated with an increase of 866 (95% CI
      762 to 970; p<0.001) in the rate of primary care consultations. The FHS was not
      significantly associated with a reduction in hospitalisations for any of the 19
      conditions. Conclusions: While high-quality primary healthcare can deliver
      considerable health benefits to the population, it may not always be effective in
      addressing inefficiencies at the hospital level due to avoidable admissions.

PMID- 29225927
TI  - Institutionalising health technology assessment: establishing the Medical
      Technology Assessment Board in India.
AB  - India is at crossroads with a commitment by the government to universal health
      coverage (UHC), driving efficiency and tackling waste across the public
      healthcare sector. Health technology assessment (HTA) is an important policy
      reform that can assist policy-makers to tackle inequities and inefficiencies by
      improving the way in which health resources are allocated towards cost-effective,
      appropriate and feasible interventions. The equitable and efficient distribution
      of health budget resources, as well as timely uptake of good value technologies,
      are critical to strengthen the Indian healthcare system. The government of India
      is set to establish a Medical Technology Assessment Board to evaluate existing
      and new health technologies in India, assist choices between comparable
      technologies for adoption by the healthcare system and improve the way in which
      priorities for health are set. This initiative aims to introduce a more
      transparent, inclusive, fair and evidence-based process by which decisions
      regarding the allocation of health resources are made in India towards the
      ultimate goal of UHC. In this analysis article, we report on plans and progress
      of the government of India for the institutionalisation of HTA in the country.
      Where India is home to one-sixth of the global population, improving the health
      services that the population receives will have a resounding impact not only for
      India but also for global health.

PMID- 29225928
TI  - Causes of severe visual impairment and blindness in students in schools for the
      blind in Northwest Ethiopia.
AB  - Objectives: To determine the causes of severe visual impairment and blindness
      (SVI/BL) among students in schools for the blind in Northwest Ethiopia and to
      identify preventable and treatable causes. Method: Students attending nine
      schools for the blind in Northwest Ethiopia were examined and causes assigned
      using the standard WHO record form for children with blindness and low vision in
      May and June 2015. Results: 383 students were examined, 357 (93%) of whom were
      severely visually impaired or blind (<6/60 in their better eye). 253 (70.9%) were
      aged 16 years or above and 228 (63.9%) were males. 100 students aged <16 years
      were blind and four were SVI, total 104. The major anatomical site of visual loss
      among those 0-15 years was cornea/phthisis (47.1%), usually due to measles and
      vitamin A deficiency, followed by whole globe (22.1%), lens (9.6%) and uvea
      (8.7%). Among students aged 16 years and above, corneal/phthisis (76.3%) was the
      major anatomical cause, followed by lens (6.3%), whole globe (4.7%), uvea (3.6%)
      and optic nerve (3.2%). The leading underlying aetiology among students aged <16
      years was childhood factors (39.4%) (13.5% measles, 10.6% vitamin A deficiency),
      followed by unknown aetiology (54.8%), perinatal (2.9%) and hereditary factors
      (2.9%). In the older group, childhood factors (72.3%) (25% measles, 15% vitamin A
      deficiency) were major causes, followed by unknown aetiology (24.1%), perinatal
      (2.4%) and hereditary factors (0.8%). Over 80% of the causes were avoidable with
      majority being potentially preventable (65%). Conclusion: Corneal blindness,
      mainly as the result of measles and vitamin A deficiency, is still a public
      health problem in Northwest Ethiopia, and this has not changed as observed in
      other low-income countries. More than three-fourth of causes of SVI/BL in
      students in schools for the blind are potentially avoidable, with measles/vitamin
      A deficiency and cataract being the leading causes.

PMID- 29225929
TI  - New global surgical and anaesthesia indicators in the World Development
      Indicators dataset.

PMID- 29225930
TI  - Using the Consolidated Framework for Implementation Research to implement and
      evaluate national surgical planning.
AB  - The Lancet Commission on Global Surgery defined six surgical indicators and a
      framework for a national surgical plan that aimed to incorporate surgical care as
      a part of global public health. Multiple countries have since begun national
      surgical planning; each faces unique challenges in doing so. Implementation
      science can be used to more systematically explain this heterogeneous process,
      guide implementation efforts and ultimately evaluate progress. We describe our
      intervention using the Consolidated Framework for Implementation Research. This
      framework requires identifying characteristics of the intervention, the
      individuals involved, the inner and outer setting of the intervention, and
      finally describing implementation processes. By hosting a consultative symposium
      with clinicians and policy makers from around the world, we are able to specify
      key aspects of each element of this framework. We define our intervention as the
      incorporation of surgical care into public health planning, identify local
      champions as the key individuals involved, and describe elements of the inner and
      outer settings. Ultimately we describe top-down and bottom-up models that are
      distinct implementation processes. With the Consolidated Framework for
      Implementation Research, we are able to identify specific strategic models that
      can be used by implementers in various settings. While the integration of
      surgical care into public health throughout the world may seem like an
      insurmountable challenge, this work adds to a growing effort that seeks to find a
      way forward.

PMID- 29225931
TI  - Community preferences for a social health insurance benefit package: an
      exploratory study among the uninsured in Vietnam.
AB  - Understanding public preferences in terms of health benefit packages (HBPs)
      remains limited, yet gathering community insights is an important endeavour when
      developing people-centred health systems and moving towards universal health
      coverage. Our study aimed to address this gap in knowledge by eliciting community
      preferences for the social health insurance benefit package among the uninsured
      in Vietnam. We adopted a mixed methods approach that included a ranking exercise
      followed by focus group discussions. We collected quantitative and qualitative
      data from 174 uninsured people in Bac Giang, a province in northern Vietnam.
      Study participants were purposively selected from 12 communities and assembled in
      14 group sessions that entailed three stages: participants first selected and
      ranked benefit items individually, then in groups and finally they engaged in a
      discussion regarding their decisions. The majority of respondents (both as
      individuals and as groups) preferred an HBP that covers both curative and
      preventive care, with a strong preference for the inclusion of high-cost care,
      resulting from rare and costly events (inpatient care), as well as frequent and
      less costly events (drugs, tests and outpatient care). The process of group
      discussion highlighted how individual choices could be modified in the context of
      group negotiation. The shift in preferences was motivated by the wish to protect
      low-income people from catastrophic expenditure while maximising community access
      to vital yet costly healthcare services. Future research, interventions and
      policies can built on this initial exploration of preferences to explore how
      stakeholders can engage communities and support greater public involvement in the
      development of HBPs in Vietnam and other low-income and middle-income countries.

PMID- 29225932
TI  - Potential applications of telenephrology to enhance global kidney care.
AB  - Chronic kidney disease (CKD) is an important public health issue that
      increasingly affects more patients globally and is associated with adverse
      clinical consequences with huge economic impact. Effective management of patients
      with CKD requires delivery of kidney care in a primary care setting where
      possible and at a higher level with a nephrologist when necessary to improve
      outcomes. In many instances and for various reasons, it is not possible to follow
      this pathway of care delivery. With improving telecommunication technologies
      worldwide, it is hoped that increasing utilisation of electronic communication
      devices can be used to facilitate kidney care to improve the quality of care
      delivered to patients, especially those who live in remote regions. Kidney care
      and therefore outcomes for patients with CKD is often compromised due to lack of
      access to a nephrologist, either because of distance or shortage of
      nephrologists, high proportion of patients being unaware they have CKD, lack of
      population screening for early detection of CKD and risk factors and prevention
      programmes and poor patient adherence and absence of appropriate CKD management
      strategies. Telenephrology can play a significant role in addressing these
      factors and therefore can be leveraged to improve CKD outcomes globally,
      especially in low to middle-income countries. This paper provides an overview on
      the potential role of telenephrology in enhancing access to and quality of care
      delivered to patients with CKD to improve outcomes.

PMID- 29225933
TI  - Changing views on child mortality and economic sanctions in Iraq: a history of
      lies, damned lies and statistics.
AB  - In August 1990, Saddam Hussein's army invaded Kuwait and consequently the United
      Nations imposed economic sanctions on Iraq. In 1991, an international military
      alliance expelled the Iraqi army from Kuwait during a short war. Nevertheless,
      the economic sanctions remained in place-their removal required that Iraq should
      destroy its weapons of mass destruction. Subsequent years saw reports of acute
      suffering in Iraq. The sanctions undoubtedly greatly reduced the country's
      ability to import supplies of food and medicine. Particular concerns arose about
      the state of young children. These concerns crystalised in 1999 when, with
      cooperation from the Iraqi government, Unicef conducted a major demographic
      survey. The results of the survey indicated that the under-5 death rate in Iraq
      had increased hugely between 1990 and 1991 and had then continued at a very high
      level. The survey results were used both to challenge and support the case for
      the invasion of Iraq in 2003. And they were cited by Tony Blair in 2010 in his
      testimony to the Iraq Inquiry established by the British government. Indeed, the
      results of the 1999 Unicef/Government of Iraq survey are still cited. Since 2003,
      however, several more surveys dealing with child mortality have been undertaken.
      Their results show no sign of a huge and enduring rise in the under-5 death rate
      starting in 1991. It is therefore clear that Saddam Hussein's government
      successfully manipulated the 1999 survey in order to convey a very false
      impression-something that is surely deserving of greater recognition.

PMID- 29225934
TI  - Health policy and systems research: towards a better understanding and review of
      ethical issues.
AB  - Given the focus on health systems in the post-millennium development goal era and
      moving towards the sustainable development goals, there is a compelling need for
      a common framework for health policy and systems research ethics to guide
      researchers and facilitate review by research ethics committees. A consultation
      of global health policy and systems research and ethics experts was convened to
      identify ethical considerations relevant to health policy and systems research
      based on existing knowledge and to identify knowledge gaps through a scoping
      review and further expert deliberation. Health policy and systems research is
      highly complex and, in the absence of guidance documents, there is significant
      variability in ethics review. Although fundamental ethical principles pertain to
      both traditional clinical research and health policy and systems research, the
      application of these principles requires a comprehensive understanding of the
      nature of health policy and systems research with its distinct challenges. Such
      awareness must be raised among researchers and research ethics committees.
      Current research ethics committees lack familiarity with health policy and
      systems research and because health policy and systems research is conducted in
      real-world contexts, committees often have difficulties in determining whether a
      project is indeed research and/or requires ethical review. Given the strong
      current focus on health policy and systems research to rapidly improve health and
      health systems functioning globally, greater engagement and dialogue around the
      ethical concerns is required to optimise research review and research conduct in
      this rapidly evolving field.

PMID- 29225935
TI  - Gendered negotiations for research participation in community-based studies:
      implications for health research policy and practice.
AB  - There is a growing literature documenting the complex realities of consent
      processes in the field, and the negotiations and ethical dilemmas involved. Much
      has also been written about how gender and power shape household decision-making
      processes. However, these bodies of literature have rarely been brought together
      to inform research theory and practice in low-income settings. In this paper,
      qualitative research (observation, focus group discussions and interviews) were
      used alongside large clinical community-based studies conducted on the Kenyan
      Coast to explore how gender and power relations within households and communities
      and between fieldworkers and communities shape consent processes and
      interactions. This exploration is embedded in relevant literature and the
      implications for community-based health research policy and practice are
      considered. Across diverse forms of households, we observed significant
      consultation on whether or not to participate in research. Although men are
      typically described as household decision-makers, in practice, decision-making
      processes are often far more nuanced, with many women using their agency to
      control, sometimes subtly, the decisions made. Where decisions are made without
      adequately consulting women, many find strategies to exercise their choice, in
      ways that safeguard important relationships within households in the longer term.
      We also found that the gender of field staff who typically conduct research
      activities in the field, including consent processes, can influence household
      dynamics and decision-making processes with important implications for the
      science and ethics of research. It is essential that frontline field staff and
      their supervisors are aware of the complex and gendered realities of consent
      processes at household level, and their implications, and that they develop
      appropriate context-informed approaches that support ethical practice.

PMID- 29225936
TI  - Comparative analysis of gender differences in outcomes after trauma in India and
      the USA: case for standardised coding of injury mechanisms in trauma registries.
AB  - Introduction: While females generally have better outcomes than males after
      traumatic injury, higher mortality has been shown to occur in females after
      intentional trauma in lower-income countries. However, gender differences in
      trauma outcomes in different countries have not been previously compared. We
      conducted a two-country comparative analysis to characterise gender differences
      in mortality for different mechanisms of injury. Methods: Two urban trauma
      databases were analysed from India and the USA for fall, motor vehicle collision
      (MVC) and assault patients between 2013 and 2015. Coarsened exact matching was
      used to match the two groups based on gender, age, injury severity score, Glasgow
      Coma Score and type of injury (blunt vs penetrating). The primary outcome of
      mortality was studied by using logistic regression to calculate the odds of death
      in the four country/gender subgroups. Results: A total of 10 089 and 14 144
      patients were included from the Indian and US databases, respectively. After
      matching on covariates, 7505 and 9448 patients were included in the logistic
      regression. Indian males had the highest odds of death compared with US males, US
      females and Indian females for falls, MVC and assaults. Indian females had over 7
      times the odds of dying after falls, 5 times the odds of dying for MVC and 40
      times the odds of dying after assaults when compared with US females. Conclusion:
      The high odds of death for Indian females compared with US females suggests that
      there are other injury and systemic factors that contribute to this discrepancy
      in mortality odds. This same mortality pattern and implication is seen for Indian
      males compared with all subgroups. Standardised coding of injury mechanism in
      trauma registries, in addition to intentionality of injury, can help further
      characterise discrepancies in outcomes by gender and country, to guide targeted
      injury prevention and care.

PMID- 29225937
TI  - Use of standardised patients to assess quality of healthcare in Nairobi, Kenya: a
      pilot, cross-sectional study with international comparisons.
AB  - Introduction: The quality of clinical care can be reliably measured in multiple
      settings using standardised patients (SPs), but this methodology has not been
      extensively used in Sub-Saharan Africa. This study validates the use of SPs for a
      variety of tracer conditions in Nairobi, Kenya, and provides new results on the
      quality of care in sampled primary care clinics. Methods: We deployed 14 SPs in
      private and public clinics presenting either asthma, child diarrhoea,
      tuberculosis or unstable angina. Case management guidelines and checklists were
      jointly developed with the Ministry of Health. We validated the SP method based
      on the ability of SPs to avoid detection or dangerous situations, without
      imposing a substantial time burden on providers. We also evaluated the
      sensitivity of quality measures to SP characteristics. We assessed quality of
      practice through adherence to guidelines and checklists for the entire sample,
      stratified by case and stratified by sector, and in comparison with previously
      published results from urban India, rural India and rural China. Results: Across
      166 interactions in 42 facilities, detection rates and exposure to unsafe
      conditions were both zero. There were no detected outcome correlations with SP
      characteristics that would bias the results. Across all four conditions, 53% of
      SPs were correctly managed with wide variation across tracer conditions. SPs paid
      76% less in public clinics, but proportions of correct management were similar to
      private clinics for three conditions and higher for the fourth. Kenyan outcomes
      compared favourably with India and China in all but the angina case. Conclusions:
      The SP method is safe and effective in the urban Kenyan setting for the
      assessment of clinical practice. The pilot results suggest that public providers
      in this setting provide similar rates of correct management to private providers
      at significantly lower out-of-pocket costs for patients. However, comparisons
      across countries are sensitive to the tracer condition considered.

PMID- 29225938
TI  - Health sector governance: should we be investing more?
AB  - Governance is central to improving health sector performance and achieving
      Universal Health Coverage (UHC). However, the growing body of research on
      governance and health has not yet led to a global consensus on the need for more
      investment in governance interventions to improve health. This paper aims to
      summarise the latest evidence on the influence of governance on health, examines
      how we can assess governance interventions and considers what might constitute
      good investments in health sector governance in resource constrained settings.
      The paper concludes that agendas for improving governance need to be realistic
      and build on promising in-country innovation and the growing evidence base of
      what works in different settings. For UHC to be achieved, governance will require
      new partnerships and opportunities for dialogue, between state and non-state
      actors. Countries will require stronger platforms for effective intersectoral
      actions and more capacity for applied policy research and evaluation. Improved
      governance will also come from collective action across countries in research,
      norms and standards, and communicable disease control.

PMID- 29225939
TI  - Mapping global policy discourse on antimicrobial resistance.
AB  - The rising importance of antimicrobial resistance (AMR) to the global health
      agenda is associated with a growing number of parties voicing their concern about
      the issue. With more recommendations and policies appearing, understanding the
      policy process requires making sense of the views, values, interests and goals of
      each participant. Policy frame analysis provides a method to understand both the
      scientific view and the actions advocated by global health actors to tackle AMR.
      Here we review and refine policy frame analyses of AMR using a deductive
      approach. Among several policy frames previously defined in the field of global
      health, we identify 'AMR as healthcare', 'AMR as development', 'AMR as
      innovation' and 'AMR as security' as frequent frames used in dealing with AMR. In
      addition, we found that 'AMR as One Health' constitutes a recent framing of the
      topic that seeks to provide an integrated understanding between human and animal
      health. Each frame originates in distinct scientific fields, conceptualises the
      main causes of AMR and prioritises different interventions and measurements.
      Better understanding and integration of these frames into an overarching social
      and ecological framework will support policy progress in tackling AMR.

PMID- 29225940
TI  - Chronic kidney disease and the global NCDs agenda.

PMID- 29225942
TI  - Correction: Improving the detection of environmental enteric dysfunction: a
      lactulose, rhamnose assay of intestinal permeability in children aged under 5
      years exposed to poor sanitation and hygiene.
AB  - [This corrects the article DOI: 10.1136/bmjgh-2016-000066.].

PMID- 29225941
TI  - Beyond menstrual hygiene: addressing vaginal bleeding throughout the life course
      in low and middle-income countries.
AB  - Girls and women experience numerous types of vaginal bleeding. These include
      healthy reproductive processes, such as menstruation and bleeding after
      childbirth, but also bleeding related to health conditions, such as fibroids or
      cancer. In most societies, the management of menstruation is handled covertly,
      something girls are often instructed about at menarche. The management of other
      vaginal bleeding is often similarly discreet, although behaviours are not well
      documented. In many societies, cultural taboos frequently hinder open discussion
      around vaginal bleeding, restricting information and early access to healthcare.
      Additionally, the limited availability of clean, accessible water and sanitation
      facilities in many low and middle-income countries augments the challenges girls
      and women face in conducting daily activities while managing vaginal bleeding,
      including participating in school or work, going to the market or fetching water.
      This paper aims to highlight the key vaginal bleeding experiences throughout a
      woman's life course and the intersection of these bleeding experiences with their
      access to adequate water and sanitation facilities, information and education
      sources, and supplies. The aim is to address the silence around girls and women's
      vaginal bleeding and their related social, physical and clinical management needs
      across the life course; and highlight critical gaps that require attention in
      research, practice and policy around this neglected topic of health and gender
      equality.

PMID- 29225943
TI  - How income and food prices influence global dietary intakes by age and sex:
      evidence from 164 countries.
AB  - Background: While income and prices are key drivers of dietary choices, how their
      influence varies by food category, nation, and demographics is not well
      established. Based on intake data for 164 countries and 11 food categories, we
      examined how income and food prices relate to food intake globally, including by
      world region, age, and sex. Methods: We used 2010 intake data from the Global
      Dietary Database, the first database of consumption estimates for major food
      categories by country, age, and sex. We combined these data with national per
      capita GDP and food price data. We estimated intake responsiveness to income and
      prices for each food category, accounting for differences by national income,
      world region, age, and sex. Results: We identified several differences in intake
      responsiveness. For example, rising income was estimated to increase milk intake
      most strongly in Sub-Saharan Africa and fruit intake most strongly among older
      women globally. Comparing our intake results to previous findings based on
      expenditure data, we found more goods that exhibited declining intake in response
      to rising incomes, fewer significant relationships for a number of food
      categories, particularly for higher income regions, and whereas in prior studies,
      elasticities mostly decrease with national income, we identified food categories
      where this was not the case. Conclusion: The results of this study show
      heterogeneous associations among income, prices, and food intakes. Policymakers
      should consider the price and income elasticities of certain foods, as well as
      the role of demographics within and across countries, as they address global
      nutrition and health challenges.

PMID- 29225944
TI  - Biopsychosocial factors associated with chronic low back pain disability in rural
      Nigeria: a population-based cross-sectional study.
AB  - Introduction: Many people in Nigeria are living with disability due to chronic
      low back pain (CLBP), with the greatest burden accounted for by people living in
      rural Nigeria. However, factors associated with disability in rural Nigeria have
      not yet been established. We investigated the biomechanical and psychosocial
      predictors of CLBP disability in a rural Nigerian population. Methods: A cross
      sectional study of adults with non-specific CLBP recruited from rural communities
      in Enugu State, South-eastern Nigeria. Measures of self-reported and performance
      based disability, pain intensity, anxiety and depression, coping strategies,
      social support, occupational biomechanical factors, illness perceptions and fear
      avoidance beliefs were collected by trained community health workers. We used
      univariate and multivariate analyses. Results: 200 individuals were recruited.
      Psychosocial factors were the most important factors associated with CLBP
      disability, and accounted for 62.5% and 49.1% of the variance in self-reported
      and performance-based disability, respectively. The significant predictors of
      self-reported disability were: illness perceptions (beta=0.289; p<0.0005), pain
      intensity (beta=0.230; p<0.0005), catastrophising (beta=0.210; p=0.001), fear
      avoidance beliefs (beta=0.198; p=0.001) and anxiety (beta=0.154; p=0.023). The
      significant predictors of performance-based disability were: illness perceptions
      (beta=0.366; p<0.0005), social support (beta=0.290; p<0.0005), fear avoidance
      beliefs (beta=0.189; p<0.01) and female gender (beta=0.184; p<0.01). Illness
      concern was the most salient dimension of illness perceptions predicting self
      reported and performance-based disability. Conclusions: These results provide
      evidence which can be used to inform the development of interventions to reduce
      CLBP disability in rural Nigeria, and may have relevance in other rural African
      contexts.

PMID- 29225945
TI  - Reproductive, maternal, neonatal and child health in conflict: a case study on
      Syria using Countdown indicators.
AB  - Introduction: Women and children account for a disproportionate morbidity burden
      among conflict-affected populations, and yet they are not included in global
      accountability frameworks for women's and children's health. We use Countdown to
      2015 (Millennium Development Goals) health indicators to provide an up-to-date
      review and analysis of the best available data on Syrian refugees in Jordan,
      Lebanon and Turkey and internally displaced within Syria and explore data
      challenges in this conflict setting. Methods: We searched Medline, PubMed,
      Scopus, Popline and Index Medicus for WHO Eastern Mediterranean Region Office and
      relevant development/humanitarian databases in all languages from January 2011
      until December 2015. We met in person or emailed relevant key stakeholders in
      Lebanon, Jordan, Syria and Turkey to obtain any unpublished or missing data. We
      convened a meeting of experts working with these populations to discuss the
      results. Results: The following trends were found based on available data for
      these populations as compared with preconflict Syria. Birth registration in Syria
      and in host neighbouring countries decreased and was very low in Lebanon. In
      Syria, the infant mortality rate and under-five mortality rate increased, and
      coverage of antenatal care (one visit with a skilled attendant), skilled birth
      attendance and vaccination (except for DTP3 vaccine) declined. The number of
      Syrian refugee women attending more than four antenatal care visits was low in
      Lebanon and in non-camp settings in Jordan. Few data were available on these
      indicators among the internally displaced. In conflict settings such as that of
      Syria, coverage rates of interventions are often unknown or difficult to
      ascertain because of measurement challenges in accessing conflict-affected
      populations or to the inability to determine relevant denominators in this
      dynamic setting. Conclusion: Research, monitoring and evaluation in humanitarian
      settings could better inform public health interventions if findings were more
      widely shared, methodologies were more explicit and globally agreed definitions
      and indicators were used consistently.

PMID- 29225946
TI  - Did the right to health get across the line? Examining the United Nations
      resolution on the Sustainable Development Goals.
AB  - Since the new global health and development goal, Sustainable Development Goal
      (SDG) 3, and its nine targets and four means of implementation were introduced to
      the world through a United Nations (UN) General Assembly resolution in September
      2015, right to health practitioners have queried whether this goal mirrors the
      content of the human right to health in international law. This study examines
      the text of the UN SDG resolution, Transforming our world: the 2030 Agenda for
      Sustainable Development, from a right to health minimalist and right to health
      maximalist analytic perspective. When reviewing the UN SDG resolution's text, a
      right to health minimalist questions whether the content of the right to health
      is at least implicitly included in this document, specifically focusing on SDG 3
      and its metrics framework. A right to health maximalist, on the other hand,
      queries whether the content of the right to health is explicitly included. This
      study finds that whether the right to health is contained in the UN SDG
      resolution, and the SDG metrics therein, ultimately depends on the individual
      analyst's subjective persuasion in relation to right to health minimalism or
      maximalism. We conclude that the UN General Assembly's lack of cogency on the
      right to health's position in the UN SDG resolution will continue to blur if not
      divest human rights' (and specifically the right to health's) integral
      relationship to high-level development planning, implementation and SDG
      monitoring and evaluation efforts.

PMID- 29225947
TI  - Migrants caught between tides and politics in the Mediterranean: an imperative
      for search and rescue at sea?

PMID- 29225948
TI  - Collecting data for global surgical indicators: a collaborative approach in the
      Pacific Region.
AB  - In 2015, the Lancet Commission on Global Surgery (LCoGS) recommended six surgical
      metrics to enable countries to measure their surgical and anaesthesia care
      delivery. These indicators have subsequently been accepted by the World Bank for
      inclusion in the World Development Indicators. With support from the Royal
      Australasian College of Surgeons and the Pacific Islands Surgical Association, 14
      South Pacific countries collaborated to collect the first four of six LCoGS
      indicators. Thirteen countries collected all four indicators over a 6-month
      period from October 2015 to April 2016. Australia and New Zealand exceeded the
      recommended LCoGS target for all four indicators. Only 5 of 13 countries (38%)
      achieved 2-hour access for at least 80% of their population, with a range of 20%
      (Papua New Guinea and Solomon Islands) to over 65% (Fiji and Samoa). Five of 13
      (38%) countries met the target surgical volume of 5000 procedures per 100 000
      population, with six performing less than 1600. Four of 14 (29%) countries had at
      least 20 surgical, anaesthesia and obstetric providers in their workforce per 100
      000 population, with a range of 0.9 (Timor Leste) to 18.5 (Tuvalu). Perioperative
      mortality rate was reported by 13 of 14 countries, and ranged from 0.11% to 1.0%.
      We believe it is feasible to collect global surgery indicators across the South
      Pacific, a diverse geographical region encompassing high-income and low-income
      countries. Such metrics will allow direct comparison between similar nations, but
      more importantly provide baseline data that providers and politicians can use in
      advocacy national health planning.

PMID- 29225950
TI  - Is living in a gas-flaring host community associated with being hypertensive?
      Evidence from the Niger Delta region of Nigeria.
AB  - Background: Researchers have linked gas flaring to climate change, the hastening
      of the epidemiological transition and an upsurge in the prevalence of non
      communicable diseases. We sought to determine if a relationship exists between
      residing in a gas-flaring host community and hypertension. Methods: We conducted
      an analytical cross-sectional household survey among residents of 600 households
      in three gas-flaring and three non-gas-flaring host communities in the Niger
      Delta region of Nigeria. We took geo-coordinates, administered a modified WHO
      STEPS questionnaire and built on Android mobile phones using Open-Data-Kit (ODK)
      software. We also took biological measurements and carried out descriptive and
      inferential statistical analysis using SPSS and STATA. Results: We interviewed a
      total of 912 adults: 437 (47.9%) from non-gas-flaring and 475 (52.1%) from gas
      flaring host communities. There were differences in level of education (x2=42.99;
      p=0.00), occupation category (x2=25.42; p=0.00) and BMI category (x2=15.37;
      0.003) among the two groups. The overall prevalence of hypertension was 23.7%:
      20.7% among persons living in non-gas-flaring host communities compared with
      25.3% among persons living in gas-flaring host communities (x2=2.89; p=0.89).
      Residence in a gas-flaring host community, (AdjOR=1.75; 95% CI=1.11 to 2.74) and
      mean age (AdjOR=1.05; 95% CI=1.03 to 1.07) were identified as the predictors of
      hypertension. There was a significant association between hypertension and age,
      1.05 (1.04-1.06) while the probability of being hypertensive was higher among
      residents of gas-flaring host communities between 20 to 40 years and 60 to 80
      years. Conclusion: There is a need for the relevant agencies to scale up
      environmental and biological monitoring of air pollutants. The implication of a
      possible relationship between gas-flaring and hypertension brings to the fore the
      need for interventions to regulate gas-flaring activities.

PMID- 29225949
TI  - Improving postpartum care delivery and uptake by implementing context-specific
      interventions in four countries in Africa: a realist evaluation of the Missed
      Opportunities in Maternal and Infant Health (MOMI) project.
AB  - Postpartum care (PPC) has remained relatively neglected in many interventions
      designed to improve maternal and neonatal health in sub-Saharan Africa. The
      Missed Opportunities in Maternal and Infant Health project developed and
      implemented a context-specific package of health system strengthening and demand
      generation in four African countries, aiming to improve access and quality of
      PPC. A realist evaluation was conducted to enable nuanced understanding of the
      influence of different contextual factors on both the implementation and impacts
      of the interventions. Mixed methods were used to collect data and test
      hypothesised context-mechanism-outcome configurations: 16 case studies (including
      interviews, observations, monitoring data on key healthcare processes and
      outcomes), monitoring data for all study health facilities and communities,
      document analysis and participatory evaluation workshops. After evaluation in
      individual countries, a cross-country analysis was conducted that led to the
      development of four middle-range theories. Community health workers (CHWs) were
      key assets in shifting demand for PPC by 'bridging' communities and facilities.
      Because they were chosen from the community they served, they gained trust from
      the community and an intrinsic sense of responsibility. Furthermore, if a
      critical mass of women seek postpartum healthcare as a result of the CHWs
      bridging function, a 'buzz' for change is created, leading eventually to the
      acceptability and perceived value of attending for PPC that outweighs the costs
      of attending the health facility. On the supply side, rigid vertical hierarchies
      and defined roles for health facility workers (HFWs) impede integration of
      maternal and infant health services. Additionally, HFWs fear being judged
      negatively which overrides the self-efficacy that could potentially be gained
      from PPC training. Instead the main driver of HFWs' motivation to provide
      comprehensive PPC is dependent on accountability systems for delivering PPC
      created by other programmes. The realist evaluation offers insights into some of
      the contextual factors that can be pivotal in enabling the community-level and
      service-level interventions to be effective.

PMID- 29225951
TI  - Is governance, gross domestic product, inequality, population size or country
      surface area associated with coverage and equity of health interventions?
      Ecological analyses of cross-sectional surveys from 80 countries.
AB  - Objective: To assess associations between national characteristics, including
      governance indicators, with a proxy for universal health coverage in
      reproductive, maternal, newborn and child health (RMNCH). Design: Ecological
      analysis based on data from national standardised cross-sectional surveys.
      Setting: Low-income and middle-income countries with a Demographic and Health
      Survey or a Multiple Indicator Cluster Survey since 2005. Participants: 1 246 710
      mothers and 2 129 212 children from 80 national surveys. Exposures of interest:
      Gross domestic product (GDP), country surface area, population, Gini index and
      six governance indicators (control of corruption, political stability and absence
      of violence, government effectiveness, regulatory quality, rule of law, and voice
      and accountability). Main outcomes: Levels and inequality in the composite
      coverage index (CCI), a weighted average of eight RMNCH interventions. Relative
      and absolute inequalities were measured through the concentration index (CIX) and
      slope index of inequality (SII) for CCI, respectively. Results: The average
      values of CCI (70.5% (SD=13.3)), CIX (5.3 (SD=5.1)) and mean slope index (19.8
      (SD=14.7)) were calculated. In the unadjusted analysis, all governance variables
      and GDP were positively associated with the CCI and negatively with inequalities.
      Country surface showed inverse associations with both inequality indices. After
      adjustment, among the governance indicators, only political stability and absence
      of violence was directly related to CCI (beta=6.3; 95% CI 3.6 to 9.1; p<0.001)
      and inversely associated with relative (CIX; beta=-1.4; 95% CI -2.4 to -0.4;
      p=0.007) and absolute (SII; beta=-5.3; 95% CI -8.9 to -1.7; p=0.005)
      inequalities. The strongest associations with governance indicators were found in
      the poorest wealth quintile. Similar patterns were observed for GDP. Country
      surface area was inversely related to inequalities on CCI. Conclusions: Levels
      and equity in RMNCH interventions are positively associated with political
      stability and absence of violence, and with GDP, and inversely associated with
      country surface area.

PMID- 29225952
TI  - Thirty-year trends in the prevalence and severity of female genital mutilation: a
      comparison of 22 countries.
AB  - Introduction: Female genital mutilation (FGM) harms women's health and well-being
      and is widely considered a violation of human rights. The United Nations has
      called for elimination of the practice by 2030. Methods: We used household survey
      data to measure trends in the prevalence of FGM in 22 countries. We also examined
      trends in the severity of the practice by measuring changes in the prevalence of
      flesh removal, infibulation and symbolic 'nicking' of the genitals. We evaluated
      the extent to which measurement error may have influenced our estimates by
      observing the consistency of reports for the same birth cohorts over successive
      survey waves. Results: The prevalence of all types of FGM fell in 17 of 22
      countries we examined. The vast majority of women who undergo FGM have flesh
      removed from their genitals, likely corresponding to the partial or total removal
      of the clitoris and labia. Infibulation is still practised throughout much of sub
      Saharan Africa. Its prevalence has declined in most countries, but in Chad, Mali
      and Sierra Leone the prevalence has increased by 2-8 percentage points over 30
      years. Symbolic nicking of the genitals is relatively rare but becoming more
      common in Burkina Faso, Chad, Guinea and Mali. Conclusion: FGM is becoming less
      common over time, but it remains a pervasive practice in some countries: more
      than half of women in 7 of the 22 countries we examined still experience FGM. The
      severity of the procedures has not changed substantially over time. Rigorous
      evaluation of interventions aimed at eliminating or reducing the harms associated
      with the practice is needed.

PMID- 29225954
TI  - Fighting TB stigma: we need to apply lessons learnt from HIV activism.

PMID- 29225953
TI  - What is health systems responsiveness? Review of existing knowledge and proposed
      conceptual framework.
AB  - Responsiveness is a key objective of national health systems. Responsive health
      systems anticipate and adapt to existing and future health needs, thus
      contributing to better health outcomes. Of all the health systems objectives,
      responsiveness is the least studied, which perhaps reflects lack of comprehensive
      frameworks that go beyond the normative characteristics of responsive services.
      This paper contributes to a growing, yet limited, knowledge on this topic.
      Herewith, we review the current frameworks for understanding health systems
      responsiveness and drawing on these, as well as key frameworks from the wider
      public services literature, propose a comprehensive conceptual framework for
      health systems responsiveness. This paper should be of interest to different
      stakeholders who are engaged in analysing and improving health systems
      responsiveness. Our review shows that existing knowledge on health systems
      responsiveness can be extended along the three areas. First, responsiveness
      entails an actual experience of people's interaction with their health system,
      which confirms or disconfirms their initial expectations of the system. Second,
      the experience of interaction is shaped by both the people and the health systems
      sides of this interaction. Third, different influences shape people's interaction
      with their health system, ultimately affecting their resultant experiences.
      Therefore, recognition of both people and health systems sides of interaction and
      their key determinants would enhance the conceptualisations of responsiveness.
      Our proposed framework builds on, and advances, the core frameworks in the health
      systems literature. It positions the experience of interaction between people and
      health system as the centrepiece and recognises the determinants of
      responsiveness experience both from the health systems (eg, actors, processes)
      and the people (eg, initial expectations) sides. While we hope to trigger further
      thinking on the conceptualisation of health system responsiveness, the proposed
      framework can guide assessments of, and interventions to strengthen, health
      systems responsiveness.

PMID- 29225955
TI  - Antimicrobial resistance and universal health coverage.
AB  - The WHO launched a Global Action Plan on antimicrobial resistance (AMR) in 2015.
      World leaders in the G7, G20 and the UN General Assembly have declared AMR to be
      a global crisis. World leaders have also adopted universal health coverage (UHC)
      as a key target under the sustainable development goals. This paper argues that
      neither initiative is likely to succeed in isolation from the other and that the
      policy goals should be to both provide access to appropriate antimicrobial
      treatment and reduce the risk of the emergence and spread of resistance by taking
      a systems approach. It focuses on outpatient treatment of human infections and
      identifies a number of interventions that would be needed to achieve these policy
      goals. It then shows how a strategy for achieving key attributes of a health
      system for UHC can take into account the need to address AMR as part of a UHC
      strategy in any country. It concludes with a list of recommended priority actions
      for integrating initiatives on AMR and UHC.

PMID- 29225956
TI  - Let food be thy medicine: linking local food and health systems to address the
      full spectrum of malnutrition in low-income and middle-income countries.

PMID- 29225957
TI  - Limited sterile processing capabilities for safe surgery in low-income and middle
      income countries: experience in the Republic of Congo, Madagascar and Benin.
AB  - It is highly difficult to perform safe surgery without sterile instruments, yet
      the capacity to adequately clean, disinfect and sterilise surgical instruments in
      low-income and middle-income countries is largely unknown. Sterile Processing
      Education Charitable Trust developed an assessment tool and, in partnership with
      Mercy Ships, evaluated the sterile processing capacity in 59 facilities in
      Madagascar, Benin and the Republic of Congo. This data-driven analysis paper
      illustrates how lack of sterile processing capacity acts as a barrier to safe
      surgical care. Our tool identified widespread lack of knowledge of techniques and
      resources needed for sterile processing. Only 12% of workers in Republic of Congo
      and Benin had sterile processing training and none in Madagascar. None of the
      hospitals surveyed met basic standards for cleaning, disinfection and
      sterilisation as defined by the WHO/Pan American Health Organization. Examples of
      poor practice included lack of cleaning supplies (basic brushes and detergents),
      incorrect drying and storage of surgical instruments, and inattention to workflow
      causing cross-contamination. Bleach (sodium hypochlorite) solutions, damaging to
      instruments, were used universally. In our experience, using an assessment tool
      allowed identification of specific gaps in sterile processing capacity. Many of
      the gaps are amenable to simple solutions requiring minimal resources and
      achievable by most hospitals. We recommend that stakeholders seeking to
      strengthen surgical health systems in low-resource settings incorporate sterile
      processing capacity assessments and training into their programmes.

PMID- 29225958
TI  - Overcoming challenges in implementing the WHO Surgical Safety Checklist: lessons
      learnt from using a checklist training course to facilitate rapid scale up in
      Madagascar.
AB  - The WHO Surgical Safety Checklist was launched in 2009, and appropriate use
      reduces mortality, surgical site infections and complications after surgery by up
      to 50%. Implementation across low-income and middle-income countries has been
      slow; published evidence is restricted to reports from a few single institutions,
      and significant challenges to successful implementation have been identified and
      presented. The Mercy Ships Medical Capacity Building team developed a
      multidisciplinary 3-day Surgical Safety Checklist training programme designed for
      rapid wide-scale implementation in all regional referral hospitals in Madagascar.
      Particular attention was given to addressing previously reported challenges to
      implementation. We taught 427 participants in 21 hospitals; at 3-4 months
      postcourse, we collected surveys from 183 participants in 20 hospitals and
      conducted one focus group per hospital. We used a concurrent embedded approach in
      this mixed-methods design to evaluate participants' experiences and behavioural
      change as a result of the training programme. Quantitative and qualitative data
      were analysed using descriptive statistics and inductive thematic analysis,
      respectively. This analysis paper describes our field experiences and aims to
      report participants' responses to the training course, identify further
      challenges to implementation and describe the lessons learnt. Recommendations are
      given for stakeholders seeking widespread rapid scale up of quality improvement
      initiatives to promote surgical safety worldwide.

PMID- 29225959
TI  - Effect of removing the barrier of transportation costs on surgical utilisation in
      Guinea, Madagascar and the Republic of Congo.
AB  - Background: 81 million people face impoverishment from surgical costs every year.
      The majority of this impoverishment is attributable to the non-medical costs of
      care-for transportation, for food and for lodging. Of these, transportation is
      the largest, but because it is not viewed as an actual medical cost, it is
      frequently unaddressed. This paper examines the effect on surgical utilisation of
      paying for transportation. Methods: A hierarchical logistic regression was
      performed on 2692 patients presenting for surgical care to a non-governmental
      organisation operating in the Republic of the Congo, Guinea and Madagascar.
      Controlling for distance from the hospital, age, gender, the need for air travel
      and time between appointments, the effect of payment for transportation on the
      surgical no-show rate was evaluated. Results: After adjustment for observed
      confounders, paying for transportation drops the surgical no-show rate by 45% (OR
      0.55; 95% CI 0.40 to 0.77; p<0.001). Age, delay between appointments and the
      number of hours travelled for surgery also predict surgical no-show. For 28% of
      no-show patients, the cost of transportation from their homes to a nearby
      predetermined pick-up point remained a barrier, even when transportation from the
      pick-up point to the hospital was free. Conclusion: Transportation costs are a
      significant barrier to surgical care in low-resource settings, and paying for it
      halves the no-show rate. This finding highlights that decreasing demand-side
      barriers to surgical care cannot be limited only to the removal of user fees.

PMID- 29225960
TI  - Utility of Amorphous Calcium Phosphate-Based Scaffolds in Dental/Biomedical
      Applications.
AB  - Calcium phosphate (CaP) materials are important inorganic constituents in
      biological hard tissue. CaPs, including amorphous calcium phosphate (ACP) have
      been widely applied in dental and biomedical applications, such as tissue
      engineering. Scaffold constructs are commonly used as templates to create a
      biomimetic environment. This review considers ACP scaffold fabrication
      techniques, including tissue-engineered constructs with intrinsic incorporation
      of ACP as well as scaffolds formed via precipitation of mineralized solutions on
      a substrate. Attention is given to the approaches used to assess cellular and
      molecular responses elicited by ACP scaffolds, such as biocompatibility, cell
      conductivity, cell adhesion, cell differentiation, phenotypic profiles, and gene
      expression. Bioactivity of composite ACP scaffolds can be enhanced by
      incorporating biomolecules to create multi-functional properties. Herein we
      summarize the use of antibiotics, growth factors, and gene delivery systems to
      create multi-functional ACP scaffolds. Inasmuch as CaP materials have been
      investigated as drug delivery systems for many years, we briefly consider the
      potential of integrating these systems with existing ACP scaffold constructs and
      the potential for precision medicine.

PMID- 29225961
TI  - Land Use, Climate, and Water Resources-Global Stages of Interaction.
AB  - Land use and climate change can accelerate the depletion of freshwater resources
      that support humans and ecosystem services on a global scale. Here, we briefly
      review studies from around the world, and highlight those in this special issue.
      We identify stages that characterize increasing interaction between land use and
      climate change. During the first stage, hydrologic modifications and the built
      environment amplify overland flow via processes associated with runoff-dominated
      ecosystems (e.g., soil compaction, impervious surface cover, drainage, and
      channelization). During the second stage, changes in water storage impact the
      capacity of ecosystems to buffer extremes in water quantity and quality (e.g.,
      either losses in snowpack, wetlands, and groundwater recharge or gains in water
      and nutrient storage behind dams in reservoirs). During the third stage, extremes
      in water quantity and quality contribute to losses in ecosystem services and
      water security (e.g., clean drinking water, flood mitigation, and habitat
      availability). During the final stage, management and restoration strategies
      attempt to regain lost ecosystem structure, function, and services but need to
      adapt to climate change. By anticipating the increasing interaction between land
      use and climate change, intervention points can be identified, and management
      strategies can be adjusted to improve outcomes for realistic expectations.
      Overall, global water security cannot be adequately restored without considering
      an increasing interaction between land use and climate change across progressive
      stages and our ever-increasing human domination of the water cycle from
      degradation to ecosystem restoration.

PMID- 29225963
TI  - The Influence of Juvenile Graves' Ophthalmopathy on Graves' Disease Course.
AB  - Purpose: To investigate juvenile Graves' ophthalmopathy (GO) signs and compare
      Graves' disease (GD) course in patients with or without GO. Patients and Methods:
      There were analyzed data (visual acuity, proptosis, palpebral fissure
      measurements, clinical activity score (CAS), and the course of GD) of 67 children
      who have been newly diagnosed with GD. 26.9% of patients with GD had signs of
      ophthalmopathy (GO+), and 73.1% were without ophthalmopathy (GO-). Results: Upper
      eyelid retraction (72.3%), proptosis (66.7%), and soft tissue changes (27.8
      38.9%) were in GO+ patients. The palpebral fissure, CAS, and proptosis values
      were greater in the GO+ group than in the GO- group (p < 0.001). GD course in GO+
      patients was longer than that in GO- patients (p < 0.001). The duration of the
      first remission was longer in GO- than in GO+ patients (p < 0.001). The duration
      of first remission was longer than one year for 61.2% in GO- and 33.3% in GO+
      patients (p < 0.02). Conclusion: The common manifestations of juvenile GO
      patients were upper eyelid retraction, proptosis, and soft tissue involvement.
      The study demonstrates that pediatric patients with GO are more likely to have a
      severe course of autoimmune thyroid disease.

PMID- 29225962
TI  - TLR Specific Immune Responses against Helminth Infections.
AB  - Despite marked improvement in the quality of lives across the globe, more than 2
      million individuals in socioeconomically disadvantaged environments remain
      infected by helminth (worm) parasites. Owing to the longevity of the worms and
      paucity of immunologic controls, these parasites survive for long periods within
      the bloodstream, lymphatics, and gastrointestinal tract resulting in pathologic
      conditions such as anemia, cirrhosis, and lymphatic filariasis. Despite
      infection, an asymptomatic state may be maintained by the host immunoregulatory
      environment, which involves multiple levels of regulatory cells and cytokines; a
      breakdown of this regulation is observed in pathological disease. The role of TLR
      expression and function in relation to intracellular parasites has been
      documented but limited studies are available for multicellular helminth
      parasites. In this review, we discuss the unique and shared host effector
      mechanisms elicited by systemic helminth parasites and their derived products,
      including the role of TLRs and sphingolipids. Understanding and exploiting the
      interactions between these parasites and the host regulatory network are likely
      to highlight new strategies to control both infectious and immunological
      diseases.

PMID- 29225964
TI  - Chosen Vascular Risk Markers in Pseudoexfoliation Syndrome: An Age-Related
      Disorder.
AB  - Purpose: To evaluate lipids and C-reactive protein serum levels in patients with
      pseudoexfoliation syndrome (PEX) in the Polish population. Methods: 96 patients
      were studied with PEX and 79 control subjects. Total cholesterol, triglycerides,
      high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)
      cholesterol, non-HDL-cholesterol and CRP serum levels, and TG/HDL-C and TC/HDL-C
      indexes were assessed. Results: There were no significant differences in
      concentration of lipids and values of TC/HDL-C, TG/HDL-C, and non-HDL-C between
      PEX and control groups. High-sensitivity C-reactive protein was not increased in
      patients with PEX. Conclusions: Our results cast doubt on the opinion on the
      possible PEX and vascular diseases relation. Further studies on this subject are
      mandatory.

PMID- 29225965
TI  - Anti-VEGF and Beyond.

PMID- 29225966
TI  - Changes in Glaucoma Medication during the Past Eight Years and Future Directions
      in Japan Based on an Insurance Medical Claim Database.
AB  - Purpose: To investigate changes in the status of glaucoma care between 2006 and
      2013 and to predict future directions of glaucoma care in Japan. Subjects and
      Methods: Japanese subjects registered in the largest national insurance claim
      database in Japan from 2006 to 2013 were analyzed. Estimations of the number of
      glaucoma patients during the past eight years and of the number of future
      patients were calculated. Changes in prescription trends among the same patients
      in the three-year period after initiating antiglaucoma medication were also
      investigated. Results: There was a total of 3,016,000 subjects in the database.
      The proportion of glaucoma patients increased consistently from 2.5% in 2006 to
      4.5% in 2013. This trend was predicted to continue until 2025, followed by a
      constant decrease with age. The most frequently prescribed antiglaucoma
      medications were prostaglandin analogues (PGs); however, in recent years, fixed
      combination therapy has emerged as a major treatment. Among 2856 newly diagnosed
      glaucoma patients; 94.7% of the patients initially received a single medication,
      but 25% of the patients received additional medications within 3 years.
      Conclusions: The prevalence of glaucoma patients has significantly increased
      during the past eight years. The number of antiglaucoma medications continuously
      increased during the treatment period.

PMID- 29225967
TI  - Aptamers as the Agent in Decontamination Assays (Apta-Decontamination Assays):
      From the Environment to the Potential Application In Vivo.
AB  - The binding specificity and affinity of aptamers have long been harnessed as the
      key elements in the development of aptamer-based assays, particularly aptasensing
      application. One promising avenue that is currently explored based on the
      specificity and affinity of aptamers is the application of aptamers in the
      decontamination assays. Aptamers have been successfully harnessed as the
      decontamination agents to remove contaminants from the environment and to
      decontaminate infectious elements. The reversible denaturation property inherent
      in aptamers enables the repeated usage of aptamers, which can immensely save the
      cost of decontamination. Analogous to the point-of-care diagnostics, there is no
      doubt that aptamers can also be deployed in the point-of-care aptamer-based
      decontamination assay, whereby decontamination can be performed anywhere and
      anytime for instantaneous decision-making. It is also prophesied that aptamers
      can also serve more than as a decontaminant, probably as a tool to capture and
      kill hazardous elements, particularly pathogenic agents.

PMID- 29225969
TI  - Corrigendum to "The Role of Descending Modulation in Manual Therapy and Its
      Analgesic Implications: A Narrative Review".
AB  - [This corrects the article DOI: 10.1155/2015/292805.].

PMID- 29225968
TI  - Metabolic Differences between Dogs of Different Body Sizes.
AB  - Introduction: The domesticated dog, Canis lupus familiaris, has been selectively
      bred to produce extreme diversity in phenotype and genotype. Dogs have an immense
      diversity in weight and height. Specific differences in metabolism have not been
      characterized in small dogs as compared to larger dogs. Objectives: This study
      aims to identify metabolic, clinical, and microbiota differences between small
      and larger dogs. Methods: Gas chromatography/mass spectrometry, liquid
      chromatography/tandem mass spectrometry, clinical chemistry analysis, dual-energy
      X-ray absorptiometry, and 16S pyrosequencing were used to characterize blood
      metabolic, clinical, and fecal microbiome systems, respectively. Eighty-three
      canines from seven different breeds, fed the same kibble diet for 5 weeks, were
      used in the study. Results: 449 metabolites, 16 clinical parameters, and 6
      bacteria (at the genus level) were significantly different between small and
      larger dogs. Hierarchical clustering of the metabolites yielded 8 modules
      associated with small dog size. Conclusion: Small dogs had a lower antioxidant
      status and differences in circulating amino acids. Some of the amino acid
      differences could be attributed to differences in microflora. Additionally,
      analysis of small dog metabolites and clinical parameters reflected a network
      which strongly associates with kidney function.

PMID- 29225970
TI  - Dialysis Provision and Implications of Health Economics on Peritoneal Dialysis
      Utilization: A Review from a Malaysian Perspective.
AB  - End-stage renal disease (ESRD) is managed by either lifesaving hemodialysis (HD)
      and peritoneal dialysis (PD) or a kidney transplant. In Malaysia, the prevalence
      of dialysis-treated ESRD patients has shown an exponential growth from 504 per
      million population (pmp) in 2005 to 1155 pmp in 2014. There were 1046 pmp
      patients on HD and 109 pmp patients on PD in 2014. Kidney transplants are limited
      due to lack of donors. Malaysia adopts public-private financing model for
      dialysis. Majority of HD patients were treated in the private sector but almost
      all PD patients were treated in government facilities. Inequality in access to
      dialysis is visible within geographical regions where majority of HD centres are
      scattered around developed areas. The expenditure on dialysis has been escalating
      in recent years but economic evaluations of dialysis modalities are scarce.
      Evidence shows that health policies and reimbursement strategies influence
      dialysis provision. Increased uptake of PD can produce significant economic
      benefits and improve patients' access to dialysis. As a result, some countries
      implemented a PD-First or Favored Policy to expand PD use. Thus, a current
      comparative costs analysis of dialysis is strongly recommended to assist decision
      makers to establish a more equitable and economically sustainable dialysis
      provision in the future.

PMID- 29225971
TI  - Biochemical Analysis of Histone Succinylation.
AB  - Posttranslational modification (PTM) of proteins is used to regulate protein
      activity and stability. Histone PTMs are regarded as some of the most important,
      as they can directly regulate gene expression through chromatin reorganization.
      Recently, histone proteins were found to undergo succinylation, adding to other
      well-known PTMs such as acetylation, methylation, and phosphorylation. However,
      there is little information regarding the enzyme which catalyzes histone lysine
      succinylation. In fact, it is unclear whether this reaction is enzymatic. In this
      study, we tested histone succinylation activity in vitro using cell nuclear
      extracts of HepG2 cells. Although whole nuclear extracts did not show histone
      succinylation activity, we found that an SP 1.0 M KCl fraction of nuclear
      extracts indeed had such activity. These data offer the first direct evidence
      that histone succinylation is an enzymatic PTM as are other histone codes in the
      nucleus.

PMID- 29225972
TI  - Modulation of H-Reflex Depression with Paired-Pulse Stimulation in Healthy Active
      Humans.
AB  - Depression of the Hoffman reflex (H-reflex) is used to examine spinal control
      mechanisms during exercise, fatigue, and vibration and in response to training. H
      reflex depression protocols frequently use trains of stimuli; this is time
      consuming and prevents instantaneous assessment of motor neuronal excitability.
      The purpose of this study was to determine if paired-pulse H-reflex depression is
      reproducible and whether paired-pulse stimulation adequately estimates the
      depression induced by the more traditional ten-pulse train. H-reflexes were
      elicited via ten-pulse trains at 0.1, 0.2, 1, 2, and 5 Hz in ten neurologically
      intact individuals on two separate days. We measured the depression elicited by
      the second pulse (H2) and the mean depression elicited by pulses 2-10 (Hmean). H2
      was consistent at all frequencies on both days (r2 = 0.97, p < 0.05, and ICC(3,1)
      = 0.81). H2 did not differ from Hmean (p > 0.05). The results indicate that
      paired-pulse H-reflex depression has high between-day reliability and yields
      depression estimates that are comparable to those obtained via ten-pulse trains.
      Paired-pulse H-reflex depression may be especially useful for studies that
      require rapid assessment of motor neuronal excitability, such as during exercise,
      fatigue, and vibration, or to establish recovery curves following inhibition.

PMID- 29225973
TI  - Molecular Epidemiology of Rifampicin Resistance in Mycobacterium tuberculosis
      Using the GeneXpert MTB/RIF Assay from a Rural Setting in India.
AB  - The Xpert MTB/RIF assay can detect mutations in rpoB gene that confer rifampicin
      resistance (RR) using five overlapping probes (A, B, C, D, and E). In this study,
      we described our experience with the Xpert assay in a rural setting in India.
      During the study period, 3250 samples were processed. The result was unsuccessful
      in 5.7% of cases. For extrapulmonary specimens, the risk of unsuccessful result
      was higher in tissue biopsy and stool samples. Among samples positive for
      Mycobacterium tuberculosis, rifampicin resistance was indeterminate in 1.2% of
      them. Our results and a review of the literature showed that the most frequent
      mutations conferring RR were located in the region of Probe E (63.6%; 95%
      confidence interval [CI] 56.26-70.94), followed by Probe B (15.02%; 95% CI 11.94
      18.10), Probe D (13.35%; 95% CI 10.01-16.69), Probe A (4.73%; 95% CI 1.92-7.54),
      and Probe C (1.61%; 95% CI 0.67-2.54). Although the high cost of the cartridges
      precluded using the Xpert assay for routine diagnosis of tuberculosis, our
      results demonstrate that the assay can be used to diagnose RR-tuberculosis in
      rural areas with limited laboratory infrastructure and could be a convenient tool
      to investigate the molecular epidemiology of RR in resource-limited settings.

PMID- 29225974
TI  - Modulation Effects of Cordycepin on Voltage-Gated Sodium Channels in Rat
      Hippocampal CA1 Pyramidal Neurons in the Presence/Absence of Oxygen.
AB  - Our previous study revealed that cordycepin features important neuroprotective
      effects against hypoxic insult by improvement of neuronal electrophysiological
      function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the
      initial event during hypoxia/ischemia. However, no study comprehensively
      investigated cordycepin on VGSC. Hence, this study investigated modulation
      effects of cordycepin on VGSC not only in oxygen physiological conditions but
      also in acute oxygen deprivation injury conditions. Results revealed that
      cordycepin (80 MUM) reduced the amplitude of VGSC currents (INa) (77.6% of
      control, p < 0.01) within 1 min of drug exposure coupled with a negative shift in
      steady-state inactivation and prolonged recovery time course from inactivation.
      Additionally, this mild reduction on the peak of INa induced by the pretreatment
      with cordycepin can attenuate and delay the following hypoxia causing rapid
      dramatic decrease in INa with no additive change in the voltage dependence of
      inactivation. As modulation on VGSC in CA1 neurons represents the initial event
      during ischemia, we propose that suppression effect of cordycepin on VGSC is an
      important neuronal protective mechanism that may enhance neuronal tolerance to
      acute oxygen deprivation and delay hypoxia-induced neuronal injuries.

PMID- 29225976
TI  - Intensive Care in a Patient with Toxic Epidermal Necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a serious adverse drug reaction with high
      lethality, which usually requires intensive-medical care. A 44-year-old man
      developed generalized exanthema with increasing exfoliation and mucosal
      involvement after taking allopurinol, ibuprofen, and etoricoxib. The clinical
      diagnosis of TEN was histologically confirmed. Prednisolone therapy with 3 mg/kg
      body weight (BW) was not able to prevent further progress to finally 80% of the
      body surface, and infliximab 5 mg/kg BW was given as a single dose. This
      prevented further progression of the TEN. Despite marked improvement in skin
      findings, the ICU stay was prolonged by a complex analgosedation, transient
      kidney failure, volume management, positioning therapy, and vegetatively impeded
      weaning. Moreover, there was colonization with multiresistant bacteria (MRSA and
      VRE). Nonetheless, the patient could be restored to health and was released after
      four weeks. Infliximab seems to be effective in the treatment of TEN, especially
      in cases of rapid progression. Moreover, patients with TEN are difficult to
      handle in intensive-medical care, whereby attention should especially be paid to
      sufficient pain therapy, and the positioning of the patient is a particular
      challenge.

PMID- 29225975
TI  - Correlation between Traits of Emotion-Based Impulsivity and Intrinsic Default
      Mode Network Activity.
AB  - Negative urgency (NU) and positive urgency (PU) are implicated in several high
      risk behaviors, such as eating disorders, substance use disorders, and
      nonsuicidal self-injury behavior. The current study aimed to explore the possible
      link between trait of urgency and brain activity at rest. We assessed the
      amplitude of low-frequency fluctuations (ALFF) of the resting-state functional
      magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency
      measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral
      prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate,
      and posterior cingulate cortex/precuneus. In addition, trait urgency measures
      showed significant correlations with the functional connectivity of the posterior
      cingulate cortex/precuneus seed with the thalamus and midbrain region. These
      findings suggest an association between intrinsic brain activity and impulsive
      behaviors in healthy humans.

PMID- 29225977
TI  - Double Morphology: Tertiary Syphilis and Acquired Immunodeficiency Syndrome-A
      Rare Association.
AB  - Background: Human immunodeficiency virus (HIV) and Treponema pallidum coinfection
      is relatively common and accounts for about 25% of primary and secondary
      syphilis. Tertiary syphilis in HIV-uninfected and HIV-infected patients is
      vanishingly rare. This is most likely due to early treatment of cases of primary
      and secondary syphilis. There is rapid progression to tertiary syphilis in HIV
      infected patients. Case Presentation: A 49-year-old woman diagnosed with HIV Type
      1 infection and cluster of differentiation 4 (CD4) count of 482 presented with a
      four-week history of multiple crusted plaques, nodules, and ulcers on her face,
      arms, and abdomen. Her past history revealed red painful eyes six months prior to
      this presentation. She had generalized lymphadenopathy, no alopecia, and no
      palmar-plantar or mucosal lesions. There were no features suggestive of secondary
      syphilis. Neurological examination was normal. Her rapid plasma reagin test was
      positive to a titer of 64. She was treated with Penicillin G 20 mu IVI daily for
      2 weeks. Conclusion: Penicillin remains the treatment of choice in syphilitic
      infected HIV negative and HIV-infected individuals. In neurosyphilis, the dose of
      Penicillin GIVI is 18-24 mu daily for 10-14 days. This case report demonstrates
      the importance of excluding syphilis in any HIV-infected patient.

PMID- 29225978
TI  - Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient
      with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First
      Clinical Sign.
AB  - We present the clinical case of a patient who was admitted with an onset of
      diabetes mellitus (DM) with associated ketosis and whose clinical, hormonal, and
      radiological evolution revealed the presence of primary hyperparathyroidism,
      pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the
      context of multiple endocrine neoplasia type 1 (MEN1). DM is relatively common in
      cases of acromegaly, but it is not generally associated with ketosis.
      Simultaneously, the patient presented a meningioma, which is associated with
      pituitary macroadenoma only in extremely rare cases.

PMID- 29225979
TI  - Waldenstrom's Macroglobulinemia: A Report of Two Cases, One with Severe
      Retinopathy and One with Renal Failure.
AB  - We report here two cases of Waldenstrom's macroglobulinemia (WM), one with
      central nervous system (CNS) symptoms and severe retinopathy and one with renal
      failure. In both cases, the serum IgM levels exceeded 3,000 mg/dL and monoclonal
      IgM-kappa was observed in the blood. At onset, Case 1, a 63-year-old female,
      developed CNS symptoms-namely, drowsiness and syncope. Case 2, a 58-year-old
      male, had nausea and dysgeusia on admission associated with renal failure, which
      is quite rare in patients with WM. Both patients exhibited hyperviscosity-related
      retinopathy, but it was particularly severe in Case 1: she suddenly lost her
      vision after admission. However, her vision recovered completely during
      treatment. Case 2 required hemodialysis immediately after admission. Needle
      biopsy of his kidney revealed tubulointerstitial nephritis with marked
      infiltration with CD20-positive lymphoplasmacytic lymphoma cells. After
      treatment, Case 1 has been in a remission longer than 8 years, but Case 2 died of
      pneumonia in 6 months. Since the initial symptoms of WM are ambiguous and vary
      significantly and hyperviscosity-related ophthalmological problems or severe
      renal dysfunction can arise, it is essential to promptly measure serum IgM levels
      and to institute appropriate care immediately when WM is confirmed in a patient.

PMID- 29225980
TI  - Early Disseminated Lyme Disease with Carditis Complicated by Posttreatment Lyme
      Disease Syndrome.
AB  - Lyme disease is an infectious disease caused by the bacterium Borrelia
      burgdorferi. When untreated, infection may spread to the heart, nervous system,
      and joints. Cardiac involvement usually manifests as abnormalities of the
      conduction system and bradycardia. Treatment of Lyme disease is generally
      effective, with a subset of patients experiencing persistent, sometimes long-term
      symptoms called posttreatment Lyme disease syndrome.

PMID- 29225981
TI  - Tricuspid Valve Endocarditis due to Streptococcus bovis in a Patient with
      Ventricular Septal Defect: A Rare Manifestation-Case Report and Review of the
      Literature.
AB  - Streptococcus bovis endocarditis has 18%-62% association with colonic neoplasms
      with multivalvular involvement and affects mainly elderly males leading to severe
      cardiac dysfunction, septic embolization, and neurological complications. The
      aortic valve is the commonest valve to be affected followed by aortic and mitral
      valves together. However, involvement of tricuspid valve is extremely rare. There
      are no reported cases of Streptococcus bovis endocarditis affecting the tricuspid
      valve in the presence of ventricular septal defect with left to right shunt. We
      report the case of a 25-year-old female with ventricular septal defect who was
      diagnosed to have tricuspid valve endocarditis caused by Streptococcus bovis. Her
      detailed colonoscopy, upper gastrointestinal endoscopy, liver biochemistry, and
      ultrasound scan of the abdomen were normal. She made a very good recovery with
      six weeks of intravenous antibiotics. This is the first case of tricuspid valve
      endocarditis caused by Streptococcus bovis in association with ventricular septal
      defect without any colonic lesions.

PMID- 29225982
TI  - Sarcomatoid Renal Cell Carcinoma in an Adolescent with Sickle Cell Anaemia.
AB  - Malignancies have been reported to occur in people with sickle cell disease.
      Renal medullary carcinoma (RMC), also tagged seventh sickle cell nephropathy, is
      an aggressive cancer seen almost exclusively in people with sickle cell disease
      with more than 160 cases reported worldwide, but only few cases were reported in
      patients with sickle cell anaemia (HBSS) and from Nigeria. Sarcomatoid renal cell
      carcinoma is a renal tumour of any histologic variant containing foci of high
      grade malignant spindle cells. We report an adolescent girl with sickle cell
      anaemia (HBSS) who presented with left renal tumour, histology of which confirmed
      a diagnosis of sarcomatoid renal cell carcinoma (sRCC). Surgical debulking and
      palliative care with chemotherapy were given, and she demised 10 months after.
      The rarity of the case and challenges of managing a cancer in the background of a
      chronic haematologic disorder are highlighted.

PMID- 29225983
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report and
      Review of the Literature.
AB  - Breast implant-associated anaplastic large T-cell lymphoma has recently been
      recognized as an entity, with few reports describing the two common subtypes: in
      situ (indolent) and infiltrative. Recently, the infiltrative subtypes have been
      shown to be more aggressive requiring adjuvant chemotherapy. We report a rare
      case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in a
      65-year-old Caucasian female following silicone breast implantation and multiple
      capsulectomies. We discuss the rare presentation of this disease, histopathologic
      features of the indolent and infiltrative subtypes of ALCL, and their clinical
      significance. We also review the literature for up-to-date information on the
      diagnosis and clinical management. Treatment modalities including targeted
      therapy are also discussed. Although BIA-ALCL is rare, it should always be
      considered as part of the differential diagnosis especially in women with breast
      implants. Given the increasing rate of breast reconstruction and cosmetic
      surgeries, we anticipate a continuous rise in incidence rates of this rare
      disease; thus, caution must be taken to avoid misdiagnosis.

PMID- 29225984
TI  - Acquired von Willebrand Disease Associated with Monoclonal Gammopathy of Unknown
      Significance.
AB  - We present a case of a 79-year-old male who presented with retroperitoneal
      hematoma a week after motor vehicle accident. Prior history and family history of
      bleeding were nonsignificant. His activated partial thromboplastin time was found
      to be prolonged in the emergency department. Further workup with coagulation
      studies showed decreased factor VIII, vWF antigen, and vWF:ristocetin cofactor
      assay, and negative Bethesda assay, indicating acquired von Willebrand disease.
      Immunofluorescence to find an underlying etiology was suggestive of MGUS.
      Management of AvWD depends on controlling active bleeding and treating the
      underlying cause. He was treated with factor VIII, haemate-p, rituximab, two
      cycles of IVIg, and three weeks of oral steroids.

PMID- 29225985
TI  - Late Onset Descemet Membrane Detachment after Radial Keratotomy Resolved with
      Medical Therapy.
AB  - Purpose: To report a case of a Descemet membrane's (DM) detachment after radial
      keratotomy (RK). Methods: A patient (male) underwent RK (16 cuts) 20 years before
      referring to the Eye Center of Humanitas (Milan) for a progressive visual loss.
      The slit-lamp examination showed severe corneal stromal edema and a large DM
      detachment in the lower half of the cornea. Anterior segment optical coherence
      tomography (AS-OCT) and endothelial cells count confirmed DM detachment and
      endothelial cells damage. Descemet Stripping Automated Endothelial Keratoplasty
      (DSAEK) was planned and topical hypertonic therapy was prescribed before the
      surgery. Results: Eight months later, the patient mentioned a spontaneous
      increase in visual acuity; the slit-lamp examination and the AS-OCT displayed a
      recovery of corneal transparency with a resolution of DM detachment. Conclusions:
      This is the first report of spontaneous DM detachment with severe corneal edema
      after RK. We suggest that hypertonic therapy may reduce DM detachment and restore
      corneal transparency.

PMID- 29225986
TI  - Intranodal Palisaded Myofibroblastoma in a Submandibular Lymph Node.
AB  - Intranodal palisaded myofibroblastoma (IPM), also known as "intranodal
      hemorrhagic spindle cell tumor with amianthoid fibers," is a rare benign
      mesenchymal tumor originating from smooth muscle cells and myofibroblasts, often
      with the presence of amianthoid fibers. Usually IPM affects inguinal lymph nodes,
      but three cases have been described in the submandibular and cervical lymph
      nodes. We report a new case of a 44-year-old women with submandibular mass.
      Cervical ultrasound showed a suspect right submandibular adenomegaly. The patient
      underwent an excision of the submandibular mass. Histological features of the
      tumor include an encapsulated fusocellular proliferation, with nuclear
      palisading, amianthoid fibers, hemosiderin pigment, and extravasated
      erythrocytes. In the light of these results, we made the diagnosis of IPM. No
      recurrence was found 5 years after surgery.

PMID- 29225987
TI  - Daptomycin-Induced Acute Eosinophilic Pneumonia: Late Onset and Quick Recovery.
AB  - Background: Daptomycin is a cyclic lipopeptide antibiotic that provides great
      coverage for gram positive cocci. From the early years of daptomycin use,
      concerns were raised regarding the pulmonary side effects of daptomycin and
      potential development of acute eosinophilic pneumonia (AEP) secondary to
      daptomycin therapy. Discussion: AEP could be idiopathic or induced by drugs or
      toxins. It is a distinct entity from atopic diseases and autoimmune, parasitic,
      or fungal infections that can also cause pulmonary eosinophilia. Multiple
      medications are associated with acute eosinophilic pneumonia. Multiple cases of
      daptomycin-induced AEP have been reported in the literature. Diagnosis of AEP is
      based on clinical history, laboratory tests, and radiographic studies. Obtaining
      bronchoalveolar lavage or lung biopsy is needed to confirm the diagnosis. Timing
      of the drug use and clinical presentation is crucial in the diagnosis of drug
      induced AEP. Discontinuation of the offending drug and systemic corticosteroids
      are the mainstay treatment with great outcomes and recovery. Conclusion: We
      present a case of AEP caused by daptomycin, with complete recovery after
      discontinuation of daptomycin and administration of steroids. The patient had AEP
      after almost 6 weeks of daptomycin therapy which has never been reported in
      literature and our patient achieved complete recovery with appropriate
      management.

PMID- 29225988
TI  - Effective Administration of Rituximab in Anti-MDA5 Antibody-Positive
      Dermatomyositis with Rapidly Progressive Interstitial Lung Disease and Refractory
      Cutaneous Involvement: A Case Report and Literature Review.
AB  - We describe the case of a 48-year-old man with dermatomyositis (DM) who
      demonstrated rapidly progressive interstitial lung disease (RP-ILD) and
      refractory cutaneous involvement together with high levels of anti-melanoma
      differentiation-associated gene 5 antibody (anti-MDA5-Ab). Even after combination
      immunosuppressive therapy including a corticosteroid, cyclosporine A, and
      intravenous cyclophosphamide, his respiratory insufficiency and cutaneous
      involvement progressively worsened. However, the administration of rituximab
      (RTX) resulted in clinical remission as well as a visible reduction in anti-MDA5
      Ab levels, suggesting that RTX could be a useful remedy in cases refractory to
      conventional immunosuppressive agents, especially those of RP-ILD related to anti
      MDA5-Ab-positive DM.

PMID- 29225989
TI  - Case Report of Foreign Body Stuck in Esophagus with Failure of Endoscopic
      Management in a Man with a History of Pica.
AB  - This is a case report of foreign body ingestion in a 55-year-old intellectually
      disabled man with a history of pica and previous removal of ten plastic gloves
      from his rectum four months prior to this presentation. The patient presented
      after ingesting plastic gloves which formed large, rigid esophageal and gastric
      bezoars that were not amenable to endoscopic removal. An exploratory laparotomy
      and gastrostomy was performed, and a 10 * 4.5 * 2 cm gastric bezoar consisting of
      rigid plastic gloves was removed without complication. Special considerations
      must be taken when considering the ingestion of nonfood items in the
      intellectually disabled population as these cases may not present classically
      with symptoms of a gastric bezoar.

PMID- 29225990
TI  - Cholecystectomy of an Intrahepatic Gallbladder in an Ectopic Pelvic Liver: A Case
      Report and Review of the Literature.
AB  - Introduction: Ectopic pelvic liver is an exceedingly rare condition usually
      resulting after repair of congenital abdominal wall defects. Intrahepatic
      gallbladder is another rare condition predisposing patients to cholelithiasis and
      its sequelae. We describe a cholecystectomy in a patient with an intrahepatic
      gallbladder in a pelvic ectopic liver. Presentation of Case: A 33-year-old woman
      with a history of omphalocele repair as an infant presented with signs and
      symptoms of symptomatic cholelithiasis and chronic cholecystitis, however, in an
      unusual location. After extensive workup and symptomatic treatment,
      cholecystectomy was recommended and performed via laparotomy and hepatotomy using
      microwave technology for parenchymal hepatic transection. Discussion: Given the
      rare combination of an intrahepatic gallbladder and an ectopic pelvic liver,
      advanced surgical techniques must be employed for cholecystectomies, in addition
      to involvement of hepatobiliary experienced surgeons due to the distortion of the
      biliary and hepatic vascular anatomy. Conclusion: Cholecystectomy by experienced
      hepatobiliary surgeons is a safe and effective treatment for cholecystitis in
      patients with intrahepatic gallbladders in ectopic pelvic livers.

PMID- 29225991
TI  - Administration of Protein Kinase D1 Induces a Protective Effect on
      Lipopolysaccharide-Induced Intestinal Inflammation in a Co-Culture Model of
      Intestinal Epithelial Caco-2 Cells and RAW264.7 Macrophage Cells.
AB  - Inflammatory bowel diseases (IBD) are chronic inflammatory diseases involving all
      or part of the gastrointestinal tract. The stress-activated serine-threonine
      protein kinase D1 (PKD1) protein has previously been implicated in intestinal
      immune regulation. The objective of this study was to evaluate the effects of
      human PKD1 in relation to intestinal inflammation, using a co-culture model of
      intestinal epithelial Caco-2 cells and RAW264.7 macrophages. An inflammatory
      response was induced in the macrophages by lipopolysaccharide (LPS), upregulating
      the expression of tumour necrosis factor alpha (TNF-alpha), interleukin- (IL-)
      1beta, and IL-6 besides increasing the secretion of TNF-alpha protein. The effect
      of administering PKD1 to Caco-2 was evaluated in relation to both amelioration of
      inflammation and the ability to suppress inflammation initiation. Administration
      of PKD1 (10-100 ng/ml) following induction of inflammation induced downregulation
      of TNF-alpha expression in RAW264.7 cells. In addition, PKD1 administered for 3 h
      prior to LPS stimulation reduced the subsequent inflammatory response through
      downregulation of TNF-alpha, IL-1beta, and IL-6 in RAW264.7 cells. These results
      demonstrate a potential role of PKD1 in the intercellular communication between
      intestinal epithelial and immune cells, proposing a protective effect of PKD1 on
      the induction of an inflammatory response in macrophages, an important aspect
      during the pathogenesis of IBD.

PMID- 29225992
TI  - CART Peptide Regulates Psychostimulant-Induced Activity and Exhibits a Rate
      Dependency.

PMID- 29225993
TI  - Determination of Selected Metals in Fruit Wines by Spectroscopic Techniques.
AB  - Background: The determination of metals in different types of food and beverages
      samples has drawn significant attention due to several reasons with the most
      important one being the nutritional and toxic effects of these elements or their
      compounds. The knowledge of certain elements content in wines/fruit wines is of
      special interest due to their toxicity in case of excessive intake and also the
      effect they seem to have on the organoleptic properties of wine. Results: The
      study was focused on measuring the concentration levels of trace metals in fruit
      wines. Analysis of K, Ca, Fe, Zn, Cd, Mg, Pb, Sn, and Hg in so-called homemade
      fruit wine was carried out by AES, AAS, CV-AAS, and GF-AAS techniques. The
      calculated calibration curves showed good linearity range for all tested analytes
      (with coefficient of determination in the range from 0.989 to 0.999). The low
      values of the limit of detection (from 0.0031 MUg/L to 0.47 mg/L) and the limit
      of quantification (from 0.009 MUg/L to 1.41 mg/L) were obtained. Conclusions: The
      allowed levels of metal in fruit wines are prescribed by the International Office
      for Grapes and Wines (OIV). The data obtained from the study area for all metals
      did not exceed the international limits.

PMID- 29225994
TI  - Red Wine Age Estimation by the Alteration of Its Color Parameters: Fourier
      Transform Infrared Spectroscopy as a Tool to Monitor Wine Maturation Time.
AB  - Color, phenolic content, and chemical age values of red wines made from Cretan
      grape varieties (Kotsifali, Mandilari) were evaluated over nine months of
      maturation in different containers for two vintages. The wines differed greatly
      on their anthocyanin profiles. Mid-IR spectra were also recorded with the use of
      a Fourier Transform Infrared Spectrophotometer in ZnSe disk mode. Analysis of
      Variance was used to explore the parameter's dependency on time. Determination
      models were developed for the chemical age indexes using Partial Least Squares
      (PLS) (TQ Analyst software) considering the spectral region 1830-1500 cm-1. The
      correlation coefficients (r) for chemical age index i were 0.86 for Kotsifali
      (Root Mean Square Error of Calibration (RMSEC) = 0.067, Root Mean Square Error of
      Prediction (RMSEP) = 0,115, and Root Mean Square Error of Validation (RMSECV) =
      0.164) and 0.90 for Mandilari (RMSEC = 0.050, RMSEP = 0.040, and RMSECV = 0.089).
      For chemical age index ii the correlation coefficients (r) were 0.86 and 0.97 for
      Kotsifali (RMSEC 0.044, RMSEP = 0.087, and RMSECV = 0.214) and Mandilari (RMSEC =
      0.024, RMSEP = 0.033, and RMSECV = 0.078), respectively. The proposed method is
      simpler, less time consuming, and more economical and does not require chemical
      reagents.

PMID- 29225995
TI  - Psychometric Evaluation of the Persian Version of Barkley Adult Attention
      Deficit/Hyperactivity Disorder Screening Tool among the Elderly.
AB  - Background: The Barkley Adult Attention Deficit/Hyperactivity Disorder (ADHD)
      Rating Scale-IV (BAARS-IV) was developed, and it demonstrated good psychometric
      properties. The BAARS-IV includes 27 questions on the symptoms of adult ADHD. The
      purpose of the present study is to investigate the psychometric testing of the
      Persian version of BAARS-IV among the elderlies in Tabriz City. Method: This
      cross-sectional study was conducted in Tabriz City-in the west of Iran-in 2015
      via enrolling of 121 old-aged people. We did the process of translation and
      adaptation of BAARS-IV and examined its concurrent validity, internal
      consistency, and test-retest reliability. Result: The BAARS-IV demonstrated good
      internal consistency and test-retest reliability. Correlations between the BAARS
      IV and the CAARS-S: SV were high and evidence supporting concurrent validity was
      revealed. Cronbach's alpha for the overall scale and subscales stood at 0.89,
      0.81, 0.66, 0.56, and 0.82, respectively. Conclusion: The Persian BAARS-IV showed
      acceptable reliability and validity. BAARS-IV was determined to be composed of
      internally consistent and psychometrically sound items.

PMID- 29225996
TI  - Value and Financial Toxicity of New Cancer Drugs.

PMID- 29225997
TI  - Beyond BRCA: A Pilot Program to Assess and Improve Knowledge of Pharmacogenomic
      Testing Among Advanced Practitioners in a Breast Cancer Treatment Setting.
AB  - To provide the best available evidence-based care to their patients, advanced
      practitioners (APs) must become proficient in genomic competencies and remain
      informed regarding the availability of pharmacogenomic tests. Databases, such as
      the Centers for Disease Control and Prevention's "Genomic Testing," provide
      guidance about pharmacogenomic testing, but many APs are not aware of these
      resources. This study employed a quasi-experimental pretest/posttest design using
      a convenience sample of APs in a large clinical outpatient breast cancer clinic
      to assess the knowledge base, beliefs, attitudes, and barriers regarding
      pharmacogenomic testing among front-line APs and increase knowledge through a
      targeted educational intervention. The objectives of the educational intervention
      were to (1) increase knowledge of the clinical indication for testing; (2)
      increase collaboration among the interprofessional team; and (3) identify
      correctly when the plan of care should be modified based on pharmacogenomic test
      results to optimize patient outcomes. Responses showed that these oncology APs
      possess a strong foundation in genetics and support the addition of new
      pharmacogenomic tests to their practice.

PMID- 29225998
TI  - Multigene Panel Testing for Hereditary Cancer Risk.

PMID- 29225999
TI  - Effectiveness of Granulocyte Transfusions in Neutropenic Adult Oncology Patients:
      A Comprehensive Review of the Literature.
AB  - Among patients with cancer, many factors can cause severe and persistent
      neutropenia, leading to increased morbidity and mortality. For patients with
      neutrophil deficiency, replacement with granulocyte transfusion (GTX) seems a
      rational approach. However, existing data on the efficacy of GTX have been
      inconclusive, and such adverse effects as respiratory distress and death indicate
      the need for further investigation into its efficacy. The purpose of this
      literature review was to address the question, "Are granulocyte transfusions
      effective in the management of adult oncology patients with neutropenia?" The
      focus was on adequate dosing, optimal timing of initiation, and adverse effects.
      Implications for practice for the provider and the niche population of
      neutropenic adult oncology patients that might benefit from GTX are presented.

PMID- 29226000
TI  - Optimizing the Teachable Moment for Health Promotion for Cancer Survivors and
      Their Families.

PMID- 29226001
TI  - Ruxolitinib in Myelofibrosis and Polycythemia Vera.

PMID- 29226002
TI  - Trifluridine/Tipiracil: Old Drug, New Tricks.

PMID- 29226003
TI  - Assessment of Constipation in Patients With Cancer.

PMID- 29226005
TI  - Active Sensing for Continuous State and Action Spaces via Task-Action Entropy
      Minimization.
AB  - In this paper, a new task-oriented active-sensing method is presented. Most
      active sensing methods choose sensing actions that minimize the uncertainty of
      the state according to some information-theoretic measure. While this is
      reasonable for most applications, minimizing state uncertainty may not be most
      relevant when the state information is used to perform a task. This is because
      the uncertainty in some subspace of the state space could have more impact on the
      performance of the task than the others at a given time. The active-sensing
      method presented in this paper takes the task into account when selecting sensing
      actions by minimizing the uncertainty in future task action.

PMID- 29226004
TI  - Understanding the Context of Romantic Partner Relational Victimization: Links
      between Relationship Satisfaction, Depressive Symptoms, and Alcohol-Related
      Problems.
AB  - Objective: The purpose of this study was to examine links across romantic partner
      relational victimization, depressive symptoms, and drinking problems during young
      adulthood. We were interested in evaluating depression as a mediator of the
      association between relational victimization by one's romantic partner, drinking
      problems, and the conditional indirect effects of relationship satisfaction.
      Method: 269 individuals aged 18 to 26 years (68% female, Mage = 22.78 years, SD =
      4.70) participated in the study. They completed self-report measures online.
      Results: Mediation results indicated that depression significantly mediated the
      association between relational victimization and alcohol-related problems.
      Furthermore, tests of conditional indirect effects suggest that depression
      mediated the association between romantic partner relational victimization and
      alcohol-related problems among those who were lower in relationship satisfaction,
      but not among those who were higher in relationship satisfaction. Conclusions:
      Findings are discussed with attention to the developmental significance of
      romantic relationships during the transition to young adulthood. Specifically,
      the current findings add to the existing literature, which has suggested that
      both relationship aggression and depression are associated with problematic
      drinking.

PMID- 29226006
TI  - Next Generation Quality: Assessing the Physician in Clinical History Completeness
      and Diagnostic Interpretations Using Funnel Plots and Normalized Deviations Plots
      in 3,854 Prostate Biopsies.
AB  - Background: Observational data and funnel plots are routinely used outside of
      pathology to understand trends and improve performance. Objective: Extract
      diagnostic rate (DR) information from free text surgical pathology reports with
      synoptic elements and assess whether inter-rater variation and clinical history
      completeness information useful for continuous quality improvement (CQI) can be
      obtained. Methods: All in-house prostate biopsies in a 6-year period at two large
      teaching hospitals were extracted and then diagnostically categorized using
      string matching, fuzzy string matching, and hierarchical pruning. DRs were then
      stratified by the submitting physicians and pathologists. Funnel plots were
      created to assess for diagnostic bias. Results: 3,854 prostate biopsies were
      found and all could be diagnostically classified. Two audits involving the review
      of 700 reports and a comparison of the synoptic elements with the free text
      interpretations suggest a categorization error rate of <1%. Twenty-seven
      pathologists each read >40 cases and together assessed 3,690 biopsies. There was
      considerable inter-rater variability and a trend toward more World Health
      Organization/International Society of Urologic Pathology Grade 1 cancers in older
      pathologists. Normalized deviations plots, constructed using the median DR, and
      standard error can elucidate associated over- and under-calls for an individual
      pathologist in relation to their practice group. Clinical history completeness by
      submitting medical doctor varied significantly (100% to 22%). Conclusion: Free
      text data analyses have some limitations; however, they could be used for data
      driven CQI in anatomical pathology, and could lead to the next generation in
      quality of care.

PMID- 29226007
TI  - Houston Methodist Variant Viewer: An Application to Support Clinical Laboratory
      Interpretation of Next-generation Sequencing Data for Cancer.
AB  - Introduction: Next-generation-sequencing (NGS) is increasingly used in clinical
      and research protocols for patients with cancer. NGS assays are routinely used in
      clinical laboratories to detect mutations bearing on cancer diagnosis, prognosis
      and personalized therapy. A typical assay may interrogate 50 or more gene targets
      that encompass many thousands of possible gene variants. Analysis of NGS data in
      cancer is a labor-intensive process that can become overwhelming to the molecular
      pathologist or research scientist. Although commercial tools for NGS data
      analysis and interpretation are available, they are often costly, lack key
      functionality or cannot be customized by the end user. Methods: To facilitate NGS
      data analysis in our clinical molecular diagnostics laboratory, we created a
      custom bioinformatics tool termed Houston Methodist Variant Viewer (HMVV). HMVV
      is a Java-based solution that integrates sequencing instrument output,
      bioinformatics analysis, storage resources and end user interface. Results:
      Compared to the predicate method used in our clinical laboratory, HMVV markedly
      simplifies the bioinformatics workflow for the molecular technologist and
      facilitates the variant review by the molecular pathologist. Importantly, HMVV
      reduces time spent researching the biological significance of the variants
      detected, standardizes the online resources used to perform the variant
      investigation and assists generation of the annotated report for the electronic
      medical record. HMVV also maintains a searchable variant database, including the
      variant annotations generated by the pathologist, which is useful for downstream
      quality improvement and research projects. Conclusions: HMVV is a clinical grade,
      low-cost, feature-rich, highly customizable platform that we have made available
      for continued development by the pathology informatics community.

PMID- 29226008
TI  - Variation in Results Release and Patient Portal Access to Diagnostic Test Results
      at an Academic Medical Center.
AB  - Background: Electronic health records (EHRs) are commonplace in industrialized
      countries. Many hospitals are granting their patients access to their medical
      information through online patient portals. In this report, we describe a
      retrospective analysis of patient access to diagnostic test results released
      through the patient portal (MyChart; Epic, Inc.) at a state academic medical
      center. Methods: We analyzed 6 months of data for anatomic pathology, clinical
      laboratory, and radiology test results to evaluate variations in results release
      (automated vs. manual) and subsequent patient access to the institutional patient
      portal. During this period, diagnostic test results were released for all patient
      encounters including inpatient units, outpatient clinics, and the emergency
      department. Results: Manual results release by providers before automated release
      time occurred most commonly in the outpatient setting. The highest rates of
      access of diagnostic test results occurred for outpatients (about 30% overall
      view rate), females (two times or more compared to males in nearly every age
      bracket), and 20-45-year-old. Access rates of diagnostic tests in the emergency
      department or inpatient units were <10% across all populations. Access of
      diagnostic test results was very low for 12-17-year-old, likely influenced by
      institutional policies limiting parental proxy access within this pediatric age
      range. Approximately 20% of outpatient laboratory results were viewed by patients
      within 8 h of release from the EHR to the patient portal and 10% within 2 h of
      release. Conclusions: Patient accessing of diagnostic test results were generally
      higher for females, outpatients, and 20-45-year-old. Approximately, 20% of
      outpatient results were viewed quickly by patients after release to the EHR.

PMID- 29226009
TI  - Mechanism of Cobalt-Catalyzed CO Hydrogenation: 1. Methanation.
AB  - The mechanism of CO hydrogenation to CH4 at 260  degrees C on a cobalt catalyst
      is investigated using steady-state isotopic transient kinetic analysis (SSITKA)
      and backward and forward chemical transient kinetic analysis (CTKA). The
      dependence of CH x residence time is determined by 12CO/H2 -> 13CO/H2 SSITKA as a
      function of the CO and H2 partial pressure and shows that the CH4 formation rate
      is mainly controlled by CH x hydrogenation rather than CO dissociation. Backward
      CO/H2 -> H2 CTKA emphasizes the importance of H coverage on the slow CH x
      hydrogenation step. The H coverage strongly depends on the CO coverage, which is
      directly related to CO partial pressure. Combining SSITKA and backward CTKA
      allows determining that the amount of additional CH4 obtained during CTKA is
      nearly equal to the amount of CO adsorbed to the cobalt surface. Thus, under the
      given conditions overall barrier for CO hydrogenation to CH4 under methanation
      condition is lower than the CO adsorption energy. Forward CTKA measurements
      reveal that O hydrogenation to H2O is also a relatively slow step compared to CO
      dissociation. The combined transient kinetic data are used to fit an explicit
      microkinetic model for the methanation reaction. The mechanism involving direct
      CO dissociation represents the data better than a mechanism in which H-assisted
      CO dissociation is assumed. Microkinetics simulations based on the fitted
      parameters confirms that under methanation conditions the overall CO consumption
      rate is mainly controlled by C hydrogenation and to a smaller degree by O
      hydrogenation and CO dissociation. These simulations are also used to explore the
      influence of CO and H2 partial pressure on possible rate-controlling steps.

PMID- 29226010
TI  - Mechanism of Cobalt-Catalyzed CO Hydrogenation: 2. Fischer-Tropsch Synthesis.
AB  - Fischer-Tropsch (FT) synthesis is one of the most complex catalyzed chemical
      reactions in which the chain-growth mechanism that leads to formation of long
      chain hydrocarbons is not well understood yet. The present work provides deeper
      insight into the relation between the kinetics of the FT reaction on a silica
      supported cobalt catalyst and the composition of the surface adsorbed layer.
      Cofeeding experiments of 12C3H6 with 13CO/H2 evidence that CH x surface
      intermediates are involved in chain growth and that chain growth is highly
      reversible. We present a model-based approach of steady-state isotopic transient
      kinetic analysis measurements at FT conditions involving hydrocarbon products
      containing up to five carbon atoms. Our data show that the rates of chain growth
      and chain decoupling are much higher than the rates of monomer formation and
      chain termination. An important corollary of the microkinetic model is that the
      fraction of free sites, which is mainly determined by CO pressure, has opposing
      effects on CO consumption rate and chain-growth probability. Lower CO pressure
      and more free sites leads to increased CO consumption rate but decreased chain
      growth probability because of an increasing ratio of chain decoupling over chain
      growth. The preferred FT condition involves high CO pressure in which chain
      growth probability is increased at the expense of the CO consumption rate.

PMID- 29226011
TI  - Role of Conformational Dynamics in the Evolution of Retro-Aldolase Activity.
AB  - Enzymes exist as ensembles of conformations that are important for function.
      Tuning these populations of conformational states through mutation enables
      evolution toward additional activities. Here we computationally evaluate the
      population shifts induced by distal and active site mutations in a family of
      computationally designed and experimentally optimized retro-aldolases. The
      conformational landscape of these enzymes was significantly altered during
      evolution, as pre-existing catalytically active conformational substates became
      major states in the most evolved variants. We further demonstrate that key
      residues responsible for these substate conversions can be predicted
      computationally. Significantly, the identified residues coincide with those
      positions mutated in the laboratory evolution experiments. This study establishes
      that distal mutations that affect enzyme catalytic activity can be predicted
      computationally and thus provides the enzyme (re)design field with a rational
      strategy to determine promising sites for enhancing activity through mutation.

PMID- 29226012
TI  - Hydride Transfer versus Deprotonation Kinetics in the Isobutane-Propene
      Alkylation Reaction: A Computational Study.
AB  - The alkylation of isobutane with light alkenes plays an essential role in modern
      petrochemical processes for the production of high-octane gasoline. In this study
      we have employed periodic DFT calculations combined with microkinetic simulations
      to investigate the complex reaction mechanism of isobutane-propene alkylation
      catalyzed by zeolitic solid acids. Particular emphasis was given to addressing
      the selectivity of the alkylate formation versus alkene formation, which requires
      a high rate of hydride transfer in comparison to the competitive oligomerization
      and deprotonation reactions resulting in catalyst deactivation. Our calculations
      reveal that hydride transfer from isobutane to a carbenium ion occurs via a
      concerted C-C bond formation between a tert-butyl fragment and an additional
      olefin, or via deprotonation of the tert-butyl fragment to generate isobutene. A
      combination of high isobutane concentration and low propene concentration at the
      reaction center favor the selective alkylation. The key reaction step that has to
      be suppressed to increase the catalyst lifetime is the deprotonation of carbenium
      intermediates that are part of the hydride transfer reaction cycle.

PMID- 29226013
TI  - Novel Therapeutic Approach for Inhibition of HIV-1 Using Cell-Penetrating Peptide
      and Bacterial Toxins.
AB  - Despite advancements in our understanding of HIV-1 pathogenesis, critical virus
      components for immunity, vaccines trials, and drugs development, challenges
      remain in the fight against HIV-1. Of great importance is the inhibitory function
      of microbicidal cell penetrating peptides and bacterial toxins that interfere
      with production and neutralize infection of HIV-1 particles. We demonstrate that
      the neutralizing activity of a cationic 18 amino acids peptide, is similar to a
      broadly neutralizing human antibody, and inhibits production of two HIV-1 strains
      in human cell lines. Pretreatment of cells with bacterial toxins or toxoids
      derived from enterotoxigenic E. coli, boost subsequent activity of the peptide
      against HIV-1, to inhibit simultaneously production and infection. The synthetic
      peptide crosses the cell membrane into the cytoplasm and nucleus. In vitro
      analysis of a possible target for this peptide revealed specific binding to
      recombinant HIV-1 gag p24. This is the first demonstration of a synergy between
      bacterial toxins and a cell-penetrating peptide against HIV-1.

PMID- 29226014
TI  - The Role of Iron Metabolism in Lung Inflammation and Injury.
AB  - Iron is required for many vital functions including oxygen transport and energy
      metabolism. Protective mechanisms maintain optimal iron concentration involving
      dynamic regulation of the transporters and iron storage proteins. In addition to
      these systemic regulatory mechanisms, the unique lung environment must provide
      detoxification from metal-induced oxidative stress and pathogenic infections.
      This review focuses on the unique role of iron metabolism in lung injury and
      inflammation.

PMID- 29226016
TI  - Civic engagement and political participation among American Indians and Alaska
      natives in the US.
AB  - Within the growing literature seeking to understand civic and political
      engagement among racial and ethnic minorities, our understanding of political
      behavior among American Indian and Alaska Native's (AI/AN) remains limited. We
      use the Current Population Survey Civic Engagement and Voting and Registration
      supplements (2006-2012) to compare AI/AN voter registration, voting, and overall
      civic engagement to other racial and ethnic groups and to assess whether factors
      that predict higher levels of civic engagement vary across these populations. We
      find a few key socio-economic status indicators that predict civic and political
      engagement uniquely for AI/ANs, but they are not consistently significant across
      all years or all types of political participation. We find marital status, age,
      household size, education, and veteran status to be important in predicting civic
      engagement for AI/ANs. However, for voting and registration, we find that family
      income, age, marital status, household size, and residential stability to be
      important contributors. Although we find AI/ANs are less likely to register and
      vote compared to non-Hispanic whites, we find that the difference is not
      statistically significant in congressional years, which may suggest that AI/ANs
      are engaged in local politics and vote for representatives that will represent
      their tribal interests in national politics.

PMID- 29226015
TI  - Conserved HIV Epitopes for an Effective HIV Vaccine.
AB  - Despite major advances in antiretroviral therapy against HIV-1, an effective HIV
      vaccine is urgently required to reduce the number of new cases of HIV infections
      in the world. Vaccines are the ultimate tool in the medical arsenal to control
      and prevent the spread of infectious diseases such as HIV/AIDS. Several failed
      phase-IIb to -III clinical vaccine trials against HIV-1 in the past generated a
      plethora of information that could be used for better designing of an effective
      HIV vaccine in the future. Most of the tested vaccine candidates produced strong
      humoral responses against the HIV proteins; however, failed to protect due to: 1)
      the low levels and the narrow breadth of the HIV-1 neutralizing antibodies and
      the HIV-specific antibody-dependent Fc-mediated effector activities, 2) the low
      levels and the poor quality of the anti-HIV T-cell responses, and 3) the
      excessive responses to immunodominant non-protective HIV epitopes, which in some
      cases blocked the protective immunity and/or enhanced HIV infection. The B-cell
      epitopes on HIV for producing broadly neutralizing antibodies (bNAbs) against HIV
      have been extensively characterized, and the next step is to develop bNAb epitope
      immunogen for HIV vaccine. The bNAb epitopes are often conformational epitopes
      and therefore more difficult to construct as vaccine immunogen and likely to
      include immunodominant non-protective HIV epitopes. In comparison, T-cell
      epitopes are short linear peptides which are easier to construct into vaccine
      immunogen free of immunodominant non-protective epitopes. However, its difficulty
      lies in identifying the T-cell epitopes conserved among HIV subtypes and induce
      long-lasting, potent polyfunctional T-cell and cytotoxic T lymphocyte (CTL)
      activities against HIV. In addition, these protective T-cell epitopes must be
      recognized by the HLA prevalent in the country(s) targeted for the vaccine trial.
      In conclusion, extending from the findings from previous vaccine trials, future
      vaccines should combine both T- and B-cell epitopes as vaccine immunogen to
      induce multitude of broad and potent immune effector activities required for
      sterilizing protection against global HIV subtypes.

PMID- 29226017
TI  - Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in
      Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome.
AB  - Objective  To examine the relationship between antepartum buprenorphine dose for
      medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident
      neonatal opioid withdrawal syndrome (NOWS). Study Design  We performed a
      prospective cohort study of pregnant women with a singleton gestation diagnosed
      with OUD and receiving buprenorphine for MAT at a tertiary care academic
      institution from July 2015 to January 2017. We divided the study cohort into two
      groups-pregnancies with versus without NOWS. Substance abuse patterns in
      pregnancy, maternal, and neonatal clinical outcomes were compared. Results  The
      incidence of NOWS was 31.11% ( n  = 28/90) in our study cohort. Pregnancies with
      NOWS had a significantly higher rate of benzodiazepine positive urine tests and
      number of positive urine drug screen (UDS) results for illicit opioids. The group
      without NOWS had significantly higher number of patients with an appropriate UDS
      result at delivery through postpartum. Rates of neonatal intensive care unit
      (NICU) admission, length of NICU stay, and maximum Finnegan score were
      significantly higher in the group with NOWS. Neither the initial (10.6 +/- 5.2
      versus 10.3 +/- 4.8 mg, p  = 0.80) nor the final buprenorphine doses (13.3 +/-
      5.1 versus 13.0 +/- 4.6 mg, p  = 0.81) were significantly different between study
      groups. Conclusion  The occurrence of NOWS was not related to buprenorphine dose
      used for MAT.

PMID- 29226018
TI  - Conformal phased surfaces for wireless powering of bioelectronic microdevices.
AB  - Wireless powering could enable the long-term operation of advanced bioelectronic
      devices within the human body. Although both enhanced powering depth and device
      miniaturization can be achieved by shaping the field pattern within the body,
      existing electromagnetic structures do not provide the spatial phase control
      required to synthesize such patterns. Here, we describe the design and operation
      of conformal electromagnetic structures, termed phased surfaces, that interface
      with non-planar body surfaces and optimally modulate the phase response to
      enhance the performance of wireless powering. We demonstrate that the phased
      surfaces can wirelessly transfer energy across anatomically heterogeneous tissues
      in large animal models, powering miniaturized semiconductor devices (<12 mm3)
      deep within the body (>4 cm). As an illustration of in vivo operation, we
      wirelessly regulated cardiac rhythm by powering miniaturized stimulators at
      multiple endocardial sites in a porcine animal model.

PMID- 29226019
TI  - Absence of Acanthocytosis in Huntington's Disease-like 2: A Prospective
      Comparison with Huntington's Disease.
AB  - Background: Huntington's Disease-like 2 (HDL2) is classified as a
      neuroacanthocytosis; however, this remains unverified. We aim to determine if
      acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2
      from Huntington's disease (HD). Methods: We prospectively compared 13 HD and 12
      HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were
      prepared using international standards and reviewed by at least two blinded
      reviewers. An acanthocytosis rate of greater than 1.2% in the dry smear or
      greater than 3.7% in the wet smear was designated a priori as the threshold for
      clinical significance based on previously established standards. Flow cytometry
      was performed on all but four of the cases. Red cell membrane protein analysis
      was performed on all participants. Results: There were 12 HDL2, 13 HD, and 21
      controls enrolled. None of the HD or HDL2 participants had defined acanthocytosis
      or other morphological abnormalities. None of the HD or HDL2 cases had evidence
      of an abnormal band 3. Discussion: Acanthocytosis was not identified in either
      HDL2 or HD in our patient population. Our results, based on the first prospective
      study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will
      not help establish the diagnosis of HD or HDL2, nor differentiate between the two
      disorders and raises the question if HDL2 should be placed within the
      neuroacanthocytosis syndromes.

PMID- 29226020
TI  - Severe Bilateral Kinetic Tremor Due to Unilateral Midbrain Lesions.
AB  - Background: The dentatothalamic tract connects the dentate nucleus of the
      cerebellum with the contralateral thalamus and plays a major role in the
      pathogenesis of tremor. Unilateral lesions of the dentatothalamic pathway may
      affect its ipsilateral predecussational or its contralateral postdecussational
      course, which results either in ipsilateral or in contralateral tremor. Case
      Report: Here, we present two patients with a unilateral midbrain lesion resulting
      in bilateral tremor. Both patients presented with severe kinetic tremor.
      Discussion: The corresponding unilateral mesencephalic lesion affected both the
      ipsilateral predecussational and the ipsilateral postdecussational
      dentatothalamic tract originating from the contralateral dentate nucleus, which
      is very unusual and has not been outlined clearly before.

PMID- 29226021
TI  - Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain.
AB  - Background: The development of Holmes tremor (HT) after a direct lesion of the
      midbrain has rarely been reported in the literature, although several etiologies
      have been linked with HT, such as stroke, brainstem tumors, multiple sclerosis,
      head trauma, or infections. Phenomenology Shown: A 31-year-old male, having been
      stabbed in the right eye, presented with a rest and action tremor in the left
      upper limb associated with left hemiparesis with corresponding post-contrast
      volumetric magnetic resonance imaging T1 with sagittal oblique reformation
      showing the knife trajectory reaching the right midbrain. Educational Value:
      Despite the rarity of the etiology of HT in the present case, clinicians working
      with persons with brain injuries should be aware of this type of situation.

PMID- 29226022
TI  - Isotropic Elastic Stress Induced Large Temperature Range Liquid Crystal Blue
      Phase at Room Temperature.
AB  - A thermodynamically stable blue phase (BP) based on the conventional rod like
      nematogen is demonstrated for the first time at room temperature by only diluting
      a chiral-nematic mixture with the help of some nonmesogenic isotropic liquid. It
      is observed that addition of this isotropic liquid does not only stabilize the
      BPs at room temperature, but also significantly improves the temperature range
      (reversible during heating and cooling) of the BPs to the level of more than 28 
      degrees C. Apart from that, we have observed its microsecond electro-optic
      response time and, external electric field induced wavelength tuning, which are
      the two indispensable requirements for next generation optical devices, photonic
      displays, lasers, and many more. Here we propose that the isotropic liquid plays
      two crucial roles simultaneously. On one hand, it reduces the effective elastic
      moduli (EEM) of the BP mixtures and stabilizes the BPs at room temperature, and
      on the other hand, it increases the symmetry of the mutual orientation ordering
      among the neighboring unit cells of the BP. Hence, the resultant mixture becomes
      better resistive to some microscopic change due to the change in temperature,
      even over a large range.

PMID- 29226023
TI  - Evaluating the Whitening and Microstructural Effects of a Novel Whitening Strip
      on Porcelain and Composite Dental Materials.
AB  - Aims: The aim of this project was to evaluate the effects of 2 different
      whitening strips on color, microstructure and roughness of tea stained porcelain
      and composite surfaces. Methods: 54 porcelain and 72 composite chips served as
      samples for timed application of over-the-counter (OTC) test or control dental
      whitening strips. Chips were divided randomly into three groups of 18 porcelain
      and 24 composite chips each. Of these groups, 1 porcelain and 1 composite set
      served as controls. The remaining 2 groups were randomized to treatment with
      either Oral Essentials(r) Whitening Strips or Crest(r) 3D White WhitestripsTM.
      Sample surface structure was examined by light microscopy, profilometry and
      Scanning Electron Microscopy (SEM). Additionally, a reflectance spectrophotometer
      was used to assess color changes in the porcelain and composite samples over 24
      hours of whitening. Data points were analyzed at each time point using ANOVA.
      Results: In the light microscopy and SEM images, no discrete physical defects
      were observed in any of the samples at any time points. However, high-resolution
      SEM images showed an appearance of increased surface roughness in all composite
      samples. Using profilometry, significantly increased post-whitening roughness was
      documented in the composite samples exposed to the control bleaching strips.
      Composite samples underwent a significant and equivalent shift in color following
      exposure to Crest(r) 3D White WhitestripsTM and Oral Essentials(r) Whitening
      Strips. Conclusions: A novel commercial tooth whitening strip demonstrated a
      comparable beaching effect to a widely used OTC whitening strip. Neither
      whitening strip caused physical defects in the sample surfaces. However, the
      control strip caused roughening of the composite samples whereas the test strip
      did not.

PMID- 29226024
TI  - Polymers at Liquid/Vapor Interface.
AB  - Polymers confined to the liquid/vapor interface are studied using molecular
      dynamics simulations. We show that for polymers which are weakly immiscible with
      the solvent, the density profile perpendicular to the liquid/vapor interface is
      strongly asymmetric. On the vapor side of the interface, the density distribution
      falls off as a Gaussian with a decay length on the order of the bead diameter,
      whereas on the liquid side, the density profile decays as a simple exponential.
      This result differs from that of a polymer absorbed from a good solvent with the
      density profile decaying as a power law. As the surface coverage increases, the
      average end-to-end distance and chain mobility systematically decreases toward
      that of the homopolymer melt.

PMID- 29226025
TI  - Permeable Protein-Loaded Polymersome Cascade Nanoreactors by Polymerization
      Induced Self-Assembly.
AB  - Enzyme loading of polymersomes requires permeability to enable them to interact
      with the external environment, typically requiring addition of complex
      functionality to enable porosity. Herein, we describe a synthetic route towards
      intrinsically permeable polymersomes loaded with functional proteins using
      initiator-free visible light-mediated polymerization-induced self-assembly (photo
      PISA) under mild, aqueous conditions using a commercial monomer.
      Compartmentalization and retention of protein functionality was demonstrated
      using green fluorescent protein as a macro-molecular chromophore. Catalytic
      enzyme-loaded vesicles using horseradish peroxidase and glucose oxidase were also
      prepared and the permeability of the membrane towards their small molecule
      substrates was revealed for the first time. Finally, the interaction of the
      compartmentalized enzymes between separate vesicles was validated by means of an
      enzymatic cascade reaction. These findings have a broad scope as the methodology
      could be applied for the encapsulation of a large range of macromolecules for
      advancements in the fields of nanotechnology, biomimicry and nanomedicine.

PMID- 29226026
TI  - Ultra-Low Dispersity Poly(vinyl alcohol) Reveals Significant Dispersity Effects
      on Ice Recrystallization Inhibition Activity.
AB  - Polymer mimics of antifreeze proteins are emerging as an exciting class of
      macromolecular cryoprotectants for the storage of donor cells and tissue.
      Poly(vinyl alcohol), PVA, is the most potent polymeric ice growth inhibitor
      known, but its mode of action and the impact of valency (DP) are not fully
      understood. Herein, tandem RAFT polymerization and column chromatography are used
      to isolate oligomers with dispersities <1.01 to enable the effect of molecular
      weight distribution, as well as length, to be probed. It is found that polymers
      with equal number average molecular weight, but lower dispersity, have
      significantly less activity, which can lead to false positives when identifying
      structure-property relationships. The minimum chain length for PVA's unique
      activity, compared to other non-active poly-ols was identified. These results
      will guide the design of more active inhibitors, better cryopreservatives and a
      deeper understanding of synthetic and biological antifreeze macromolecules.

PMID- 29226028
TI  - Adolescent transgender health: Awareness does not equal resources.

PMID- 29226027
TI  - Global Burden of Skin Disease: Inequities and Innovations.
AB  - Purpose of Review: We review the current understanding of the burden of
      dermatological disease through the lens of the Global Burden of Disease project,
      evaluate the impact of skin disease on quality of life in a global context,
      explore socioeconomic implications, and finally summarize interventions towards
      improving quality of dermatologic care in resource-poor settings. Recent
      Findings: The Global Burden of Disease project has shown that skin diseases
      continue to be the 4th leading cause of nonfatal disease burden world-wide.
      However, research efforts and funding do not match with the relative disability
      of skin diseases. International and national efforts, such as the WHO List of
      Essential Medicines, are critical towards reducing the socioeconomic burden of
      skin diseases and increasing access to care. Recent innovations such as
      teledermatology, point-of-care diagnostic tools, and task-shifting help to
      provide dermatological care to underserved regions in a cost-effective manner.
      Summary: Skin diseases cause significant non-fatal disability worldwide,
      especially in resource-poor regions. Greater impetus to study the burden of skin
      disease in low resource settings and policy efforts towards delivering high
      quality care are essential in improving the burden of skin diseases.

PMID- 29226029
TI  - Diagnosis and Treatment of Ocular Pain: the Ophthalmologist's Perspective.
AB  - Purpose of Review: The aim of this review is to help ophthalmologists and other
      clinicians understand and treat ocular neuropathic pain. Recent Findings:
      Advances in the field of neurophysiology of ocular sensations explain why some
      cases of dry eye may represent a pain syndrome rather than a problem related to
      tear status. Principles related to management of pain syndromes such as
      persistent post-operative pain and complex regional pain syndrome are relevant to
      the care of these patients. Summary: Specific strategies for the ophthalmologist,
      including multimodal therapy comprised of local and systemic approaches, can be
      helpful in the care of patients with problematic ocular pain. Rather than dismiss
      these syndromes and these patients, ophthalmologists can serve these patients and
      the profession well by incorporating an understanding of ocular neuropathic pain
      into their practice and by collaboration in the care of patients with problematic
      ocular pain.

PMID- 29226030
TI  - Correction: Prevalence and correlates of psychological distress among diabetes
      mellitus adults in the Jilin province in China: a cross-sectional study.
AB  - [This corrects the article DOI: 10.7717/peerj.2869.].

PMID- 29226031
TI  - Sodium salt medium-chain fatty acids and Bacillus-based probiotic strategies to
      improve growth and intestinal health of gilthead sea bream (Sparus aurata).
AB  - Background: The increased demand for fish protein has led to the intensification
      of aquaculture practices which are hampered by nutritional and health factors
      affecting growth performance. To solve these problems, antibiotics have been used
      for many years in the prevention, control and treatment against disease as well
      as growth promoters to improve animal performance. Nowadays, the use of
      antibiotics in the European Union and other countries has been completely or
      partially banned as a result of the existence of antibiotic cross-resistance.
      Therefore, a number of alternatives, including enzymes, prebiotics, probiotics,
      phytonutrients and organic acids used alone or in combination have been proposed
      for the improvement of immunological state, growth performance and production in
      livestock animals. The aim of the present study was to evaluate two commercially
      available feed additives, one based on medium-chain fatty acids (MCFAs) from
      coconut oil and another with a Bacillus-based probiotic, in gilthead sea bream
      (GSB, Sparus aurata), a marine farmed fish of high value in the Mediterranean
      aquaculture. Methods: The potential benefits of adding two commercial feed
      additives on fish growth performance and intestinal health were assessed in a 100
      days feeding trial. The experimental diets (D2 and D3) were prepared by
      supplementing a basal diet (D1) with MCFAs in the form of a sodium salt of
      coconut fatty acid distillate (DICOSAN(r); Norel, Madrid, Spain), rich on C-12,
      added at 0.3% (D2) or with the probiotic Bacillus amyloliquefaciens CECT 5940,
      added at 0.1% (D3). The study integrated data on growth performance, blood
      biochemistry, histology and intestinal gene expression patterns of selected
      markers of intestinal function and architecture. Results: MCFAs in the form of a
      coconut oil increased feed intake, growth rates and the surface of nutrient
      absorption, promoting the anabolic action of the somatotropic axis. The probiotic
      (D3) induced anti-inflammatory and anti-oxidant effects with changes in
      circulating cortisol, immunoglobulin M, leukocyte respiratory burst, and mucosal
      expression levels of cytokines, lymphocyte markers and immunoglobulin T.
      Discussion: MCFA supplementation showed positive effects on GSB growth and
      intestinal architecture acting mainly in the anterior intestine, where absorption
      takes place. The probiotic B. amyloliquefaciens CECT 5940 exhibited key effects
      in the regulation of the immune status inducing anti-inflammatory and anti
      oxidant effects which can be potentially advantageous upon infection or exposure
      to other stressors. The potential effects of these feed additives in GSB are very
      promising to improve health and disease resistance in aquaculture.

PMID- 29226032
TI  - Resurrecting a subgenus to genus: molecular phylogeny of Euphyllia and
      Fimbriaphyllia (order Scleractinia; family Euphyllidae; clade V).
AB  - Background: The corallum is crucial in building coral reefs and in diagnosing
      systematic relationships in the order Scleractinia. However, molecular
      phylogenetic analyses revealed a paraphyly in a majority of traditional families
      and genera among Scleractinia showing that other biological attributes of the
      coral, such as polyp morphology and reproductive traits, are underutilized. Among
      scleractinian genera, the Euphyllia, with nine nominal species in the Indo
      Pacific region, is one of the groups that await phylogenetic resolution. Multiple
      genetic markers were used to construct the phylogeny of six Euphyllia species,
      namely E. ancora, E. divisa, E. glabrescens, E. paraancora, E. paradivisa, and E.
      yaeyamaensis. The phylogeny guided the inferences on the contributions of the
      colony structure, polyp morphology, and life history traits to the systematics of
      the largest genus in Euphyllidae (clade V) and, by extension, to the rest of
      clade V. Results: Analyses of cytochrome oxidase 1 (cox1), cytochrome b (cytb),
      and beta-tubulin genes of 36 colonies representing Euphyllia and a confamilial
      species, Galaxea fascicularis, reveal two distinct groups in the Euphyllia that
      originated from different ancestors. Euphyllia glabrescens formed a separate
      group. Euphyllia ancora, E. divisa, E. paraancora, E. paradivisa, and E.
      yaeyamaensis clustered together and diverged from the same ancestor as G.
      fascicularis. The 3'-end of the cox1 gene of Euphyllia was able to distinguish
      morphospecies. Discussion: Species of Euphyllia were traditionally classified
      into two subgenera, Euphyllia and Fimbriaphyllia, which represented a dichotomy
      on colony structure. The paraphyletic groups retained the original members of the
      subgenera providing a strong basis for recognizing Fimbriaphyllia as a genus.
      However, colony structure was found to be a convergent trait between Euphyllia
      and Fimbriaphyllia, while polyp shape and length, sexuality, and reproductive
      mode defined the dichotomy better. Species in a genus are distinguished by
      combining polyp morphology and colony form. The cluster of E. glabrescens of the
      Euphyllia group is a hermaphroditic brooder with long, tubular tentacles with
      knob-like tips, and a phaceloid colony structure. The Fimbriaphyllia group, with
      F. paraancora, F. paradivisa, F. ancora, F. divisa, and F. yaeyamaensis, are
      gonochoric broadcast spawners with short polyps, mixed types of tentacle shapes,
      and a phaceloid or flabello-meandroid skeleton. Soft-tissue morphology of G.
      fascicularis and Ctenella chagius were found to be consistent with the dichotomy.
      Conclusions: The paraphyly of the original members of the previous subgenera
      justify recognizing Fimbriaphyllia as a genus. The integrated approach
      demonstrates that combining polyp features, reproductive traits, and skeletal
      morphology is of high systematic value not just to Euphyllia and Fimbriaphyllia
      but also to clade V; thus, laying the groundwork for resolving the phylogeny of
      clade V.

PMID- 29226033
TI  - Patterns in artisanal coral reef fisheries revealed through local monitoring
      efforts.
AB  - Sustainable fisheries management is key to restoring and maintaining ecological
      function and benefits to people, but it requires accurate information about
      patterns of resource use, particularly fishing pressure. In most coral reef
      fisheries and other data-poor contexts, obtaining such information is challenging
      and remains an impediment to effective management. We developed the most
      comprehensive regional view of shore-based fishing effort and catch published to
      date, to show detailed fishing patterns from across the main Hawaiian Islands
      (MHI). We reveal these regional patterns through fisher "creel" surveys conducted
      by local communities, state agencies, academics, and/or environmental
      organizations, at 18 sites, comprising >10,000 h of monitoring across a range of
      habitats and human influences throughout the MHI. All creel surveys included in
      this study except for one were previously published in some form (peer-reviewed
      articles or gray literature reports). Here, we synthesize these studies to
      document spatial patterns in nearshore fisheries catch, effort, catch rates
      (i.e., catch-per-unit-effort (CPUE)), and catch disposition (i.e., use of fish
      after catch is landed). This effort provides for a description of general
      regional patterns based on these location-specific studies. Line fishing was by
      far the dominant gear type employed. The most efficient gear (i.e., highest CPUE)
      was spear (0.64 kg h-1), followed closely by net (0.61 kg h-1), with CPUE for
      line (0.16 kg h-1) substantially lower than the other two methods. Creel surveys
      also documented illegal fishing activity across the studied locations, although
      these activities were not consistent across sites. Overall, most of the catch was
      not sold, but rather retained for home consumption or given away to extended
      family, which suggests that cultural practices and food security may be stronger
      drivers of fishing effort than commercial exploitation for coral reef fisheries
      in Hawai'i. Increased monitoring of spatial patterns in nearshore fisheries can
      inform targeted management, and can help communities develop a more informed
      understanding of the drivers of marine resource harvest and the state of the
      resources, in order to maintain these fisheries for food security, cultural
      practices, and ecological value.

PMID- 29226034
TI  - Constructing a comprehensive gene co-expression based interactome in Bos taurus.
AB  - Integrating genomic information into cattle breeding is an important approach to
      exploring genotype-phenotype relationships for complex traits related to diary
      and meat production. To assist with genomic-based selection, a reference map of
      interactome is needed to fully understand and identify the functional relevant
      genes. To this end, we constructed a co-expression analysis of 92 tissues and
      this represents the systematic exploration of gene-gene relationship in Bos
      taurus. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we
      described the gene co-expression network of 5,000 protein-coding genes with
      majority variations in expression across 92 tissues. Further module
      identifications found 55 highly organized functional clusters representing
      diverse cellular activities. To demonstrate the re-use of our interaction for
      functional genomics analysis, we extracted a sub-network associated with DNA
      binding genes in Bos taurus. The subnetwork was enriched within regulation of
      transcription from RNA polymerase II promoter representing central cellular
      functions. In addition, we identified 28 novel linker genes associated with more
      than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction
      will be a valuable resource for exploring the molecular mechanisms of
      incompletely characterized proteins and for elucidating larger-scale patterns of
      functional modulization in the Bos taurus genome.

PMID- 29226035
TI  - Molecular evolution of virulence genes and non-virulence genes in clinical,
      natural and artificial environmental Legionella pneumophila isolates.
AB  - Background: L. pneumophila is the main causative agent of Legionnaires' disease.
      Free-living amoeba in natural aquatic environments is the reservoir and shelter
      for L. pneumophila. From natural water sources, L. pneumophila can colonize
      artificial environments such as cooling towers and hot-water systems, and then
      spread in aerosols, infecting the susceptible person. Therefore, molecular
      phylogeny and genetic variability of L. pneumophila from different sources
      (natural water, artificial water, and human lung tissue) might be distinct
      because of the selection pressure in different environments. Several studies
      researched genetic differences between L. pneumophila clinical isolates and
      environmental isolates at the nucleotide sequence level. These reports mainly
      focused on the analysis of virulence genes, and rarely distinguished artificial
      and natural isolates. Methods: We have used 139 L. pneumophila isolates to study
      their genetic variability and molecular phylogeny. These isolates include 51
      artificial isolates, 59 natural isolates, and 29 clinical isolates. The
      nucleotide sequences of two representative non-virulence (NV) genes (trpA, cca)
      and three representative virulence genes (icmK, lspE, lssD) were obtained using
      PCR and DNA sequencing and were analyzed. Results: Levels of genetic variability
      including haplotypes, haplotype diversity, nucleotide diversity, nucleotide
      difference and the total number of mutations in the virulence loci were higher in
      the natural isolates. In contrast, levels of genetic variability including
      polymorphic sites, theta from polymorphic sites and the total number of mutations
      in the NV loci were higher in clinical isolates. A phylogenetic analysis of each
      individual gene tree showed three to six main groups, but not comprising the same
      L. pneumophila isolates. We detected recombination events in every virulence loci
      of natural isolates, but only detected them in the cca locus of clinical
      isolates. Neutrality tests showed that variations in the virulence genes of
      clinical and environmental isolates were under neutral evolution. TrpA and cca
      loci of clinical isolates showed significantly negative values of Tajima's D, Fu
      and Li's D* and F*, suggesting the presence of negative selection in NV genes of
      clinical isolates. Discussion: Our findingsreinforced the point that the natural
      environments were the primary training place for L. pneumophila virulence, and
      intragenic recombination was an important strategy in the adaptive evolution of
      virulence gene. Our study also suggested the selection pressure had unevenly
      affected these genes and contributed to the different evolutionary patterns
      existed between NV genes and virulence genes. This work provides clues for future
      work on population-level and genetics-level questions about ecology and molecular
      evolution of L. pneumophila, as well as genetic differences of NV genes and
      virulence genes between this host-range pathogen with different lifestyles.

PMID- 29226036
TI  - Heat-Treated Stainless Steel Felt as a New Cathode Material in a Methane
      Producing Bioelectrochemical System.
AB  - Methane-producing bioelectrochemical systems (BESs) are a promising technology to
      convert renewable surplus electricity into the form of storable methane. One of
      the key challenges for this technology is the search for suitable cathode
      materials with improved biocompatibility and low cost. Here, we study heat
      treated stainless steel felt (HSSF) for its performance as biocathode. The HSSF
      had superior electrocatalytic properties for hydrogen evolution compared to
      untreated stainless steel felt (SSF) and graphite felt (GF), leading to a faster
      start-up of the biocathodes. At cathode potentials of -1.3 and -1.1 V, the
      methane production rates for HSSF biocathodes were higher than the SSF, while its
      performance was similar to GF biocathodes at -1.1 V and lower than GF at -1.3 V.
      The HSSF biocathodes had a current-to-methane efficiency of 60.8% and energy
      efficiency of 21.9% at -1.3 V. HSSF is an alternative cathode material with
      similar performance compared to graphite felt, suited for application in methane
      producing BESs.

PMID- 29226037
TI  - Parental acculturation level moderates outcome in peer-involved and parent
      involved CBT for anxiety disorders in Latino youth.
AB  - Cognitive behavioral therapies (CBTs) are efficacious treatments for anxiety
      disorders in Latino youth. However, there is a gap in knowledge about moderators
      of CBT outcomes in Latino youth. This study addresses this gap by examining
      parental acculturation as a moderator of youth anxiety outcomes in a randomized
      controlled trial of parent-involved CBT (CBT/P) and peer-involved group CBT
      (GCBT) in 139 Latino youth (ages 6 to 16 years; mean age = 9.68 years).
      Comparable youth anxiety reduction effects were found for CBT/P and GCBT.
      Parental acculturation to majority US culture, but not identification with
      country of origin, significantly moderated youth anxiety outcomes: at low levels
      of parental acculturation to majority US culture, youth posttreatment anxiety
      scores were lower in GCBT than CBT/P; at high levels of parental acculturation to
      majority US culture, youth posttreatment anxiety scores were lower in CBT/P than
      GCBT. These findings provide further evidence for the efficacy of CBTs for
      anxiety disorders in Latino youth and also provide guidance for moving toward
      personalization of CBTs' selection depending on parental acculturation levels.

PMID- 29226038
TI  - Pencil Beam Scanning Proton Therapy for Rhabdomyosarcoma of the Biliary Tract.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood with
      250-350 cases diagnosed annually in the United States. Biliary tract
      rhabdomyosarcoma is rare, representing <1% of the RMS cases. Due to its location,
      resection is clinically challenging, and functional complications exist and
      persist from biliary obstruction. The anatomical location of this tumor presents
      both opportunities and challenges for pencil beam scanning proton therapy. Proton
      therapy offers a dosimetric and clinical advantage by sparing the healthy liver,
      stomach, contra-lateral kidney and bowel. Motion management and anatomical
      variations, such as intestinal filling or weight loss, requiring routine
      dosimetric evaluation and possible adaptive treatment planning, present
      challenges for the use of proton therapy. By taking advantage of the superior
      dose distribution of proton radiation, assessing the impact of tumor and anatomy
      motion, and performing regular dose evaluations, biliary tract RMS is an ideal
      diagnosis for pencil beam scanning proton therapy.

PMID- 29226039
TI  - An Inner City Emergency Medicine Rotation Does Not Improve Attitudes toward the
      Homeless among Junior Medical Learners.
AB  - Introduction Learners in the emergency department (ED) frequently encounter
      individuals who are homeless. We sought to evaluate the effect of an inner city
      emergency medicine rotation at the Royal Alexandra Hospital (RAH) on the
      attitudes of medical students and residents towards this population. Methods Data
      were collected both pre- and post-rotation using an electronic survey. Data
      collected included demographic information and as well as scores on the Health
      Professionals' Attitudes Towards the Homeless Inventory (HPATHI). Pre- and post
      survey results were compared using Wilcoxon tests. Results Ninety-eight students
      completed the rotation. A total of 40 (41%) students completed both pre- and post
      surveys. Demographic information was available for 66 respondents. Most
      participants were male (42 {64%}), single (47 {71%}), and 30 years of age or
      younger (59 {89%}). Most participants were of a Caucasian or East/South Asian
      background (61 {92%}) and grew up in an urban setting (51 {77%}). Overall, 43
      (90%) participants saw at least one person who was homeless during their
      rotation. There was no significant difference between pre- and post-aggregate
      scores (z = -0.78, p = 0.44), or any of its three subscales (Personal Advocacy,
      Social Advocacy, and Cynicism). Conclusion First year residents and medical
      students are frequently exposed to patients who are homeless during an inner city
      ED rotation. Attitudes towards these patients did not significantly change
      following the rotation. Educational objectives should be set to improve attitudes
      of learners towards those with unstable housing throughout the ED rotation.

PMID- 29226040
TI  - Creutzfeldt Cell Rich Glioblastoma: A Diagnostic Dilemma.
AB  - Differentiating demyelinating conditions from neoplastic conditions can pose a
      significant challenge. There are a number of reports in the literature of large
      ring-enhancing, space-occupying lesions that were initially considered neoplastic
      or infectious but, on further review, were deemed demyelinating. Creutzfeldt
      Peters cells (CPC) are reactive astrocytes with fragmented nuclear inclusions
      that are routinely seen in multiple sclerosis (MS) and generally exclude the
      diagnosis of glioblastoma (GB). The patient is a 78-year-old man with a history
      of prostate cancer, which was treated with radiation therapy, who presented with
      altered mental status. A magnetic resonance imaging (MRI) scan of the brain
      revealed a 4.6 x 3.1 cm mass lesion in the right posterior temporal lobe with
      minimal mass effect and heterogeneous contrast enhancement. The patient underwent
      an open biopsy of the mass, which on histology was rich with Creutzfeldt-Peters
      cells. Frozen histology was unclear and full resection of the mass was delayed. A
      molecular and immunohistochemical analysis confirmed glioblastoma. The patient
      returned four weeks later for a subtotal resection of the tumor. The case
      presented demonstrates an example of a challenging diagnosis. Differentiating
      between demyelinating and neoplastic conditions is critical since the management
      and prognosis differ greatly. More importantly, we present a case of glioblastoma
      rich with Creutzfeldt-Peters cells, which has previously not been reported in the
      literature.

PMID- 29226041
TI  - Dapagliflozin: Cardiovascular Safety and Benefits in Type 2 Diabetes Mellitus.
AB  - Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin,
      canagliflozin, and empagliflozin, are a promising new therapy in the treatment of
      type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia
      thus improving glycemic control and they offer some beneficial effects on the
      cardiovascular (CV) system which can benefit patients with heart failure in
      addition toT2DM. The United States Food and Drug Administration requires new
      diabetes mellitus therapies to show a CV safety profile. Empagliflozin was the
      first SGLT2i that, when added to the standard of care for patients withT2DM at
      high risk for CV events, showed improved CV outcomes including reduced deaths
      from CV causes. Evidence also exists in favor of dapagliflozin for use in
      patients with T2DM with CV risk factors and heart failure. This review focuses on
      the effects, safety, and benefits of dapagliflozin on the CV system. Clinical
      trials have shown that dapagliflozin improves glycemic control without variation.
      It is safe and well-tolerated in the general population including older patients
      and those with high-risk CV factors or preexisting CV disease. There may be a
      renal protective role by an unknown mechanism. Dapagliflozin also lowers blood
      pressure due to its natriuresis effect. It improves levels of visceral fat and
      reduces body weight, and thus ameliorates metabolic syndrome. Dapagliflozin
      reduces oxidative stress and may delay atherosclerosis. Recent findings indicate
      SGLT2is may also reduce the atrial natriuretic peptide levels. Additional trials
      are required to validate these benefits and further evaluate if these are class
      effects. Trials such as DECLARE-TIMI58 are ongoing to evaluate the CV outcomes of
      dapagliflozin. More research is needed to design better antihyperglycemic regimes
      with clinical benefits in addition to good glycemic control.

PMID- 29226042
TI  - Direct Insertion of the Papillary Muscle into the Anterior Mitral Leaflet:
      Cadaveric Findings.
AB  - Direct insertion of the anterior papillary muscle (DPM) into the mitral valve is
      uncommon. During the routine dissection of an adult female, a DPM into the mitral
      valve with abnormal chordae tendinae was observed. This abnormal papillary muscle
      was measured as 28.0 mm in length from myocardial to insertion, 14.8 mm in width,
      and 7.0 mm in depth. The embryology, symptoms, associated cardiac diseases, and
      surgical precautions of this congenital malformation in the heart are reviewed.

PMID- 29226043
TI  - Applications of Whole Brain Tractography and Implications for Clinical Practice.
AB  - The complicated nature of neurological diseases-and the importance of accurate
      diagnosis and treatment for patient quality of life-have made the need for more
      advanced imaging techniques more urgent than ever. Automated whole brain
      tractography promises to increase the knowledge that neurologists have of a
      variety of disease processes, including schizophrenia, age-related changes to
      white matter, brain tumors, and epilepsy.

PMID- 29226044
TI  - Neuroanatomy and Neuropsychology of Pain.
AB  - We have reviewed here the neuroanatomical and neuropsychological literature of
      the human brain and have proposed the various pain mechanisms that we currently
      know of. Essentially when tissue is damaged, peripheral nociceptors are activated
      continuously and prostanoids are hence produced. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) and medications aim to target these prostanoids to treat the
      inflammatory component of pain. Normal pain tends to have a protective response.
      It is important for the nervous system to learn and recognize this painful
      stimulus earlier and quicker with repeated exposure to avoid tissue damage. This
      neuronal plasticity and gain in sensitivity result in sensitization of the
      nervous system, both centrally and peripherally and help in earlier detection of
      the pain sensation. However, persistent pain can become pathologic and will
      eventually result in the loss of protection pain offers to the body. Pain-related
      fear has been implicated in the transition from acute to chronic low back pain
      and the persistence of disabling low back pain, making it a key target for
      physiotherapy intervention. The current understanding of pain-related fear is
      that it is a psychopathological problem where people who catastrophise about the
      meaning of pain become trapped in a vicious cycle of avoidance behaviour, pain
      and disability, as recognised in the fear-avoidance model. We looked at how pain
      is perceived, especially in low-back pain patients. It has been hypothesized that
      individuals with low-back pain (LBP) can change their motor behavior, which is
      fundamentally an adaptation mechanism aimed at minimizing the real or perceived
      risk of further pain.

PMID- 29226045
TI  - Neuroendocrine Tumor of the Cystic Duct: A Rare and Incidental Diagnosis.
AB  - Neuroendocrine tumors (NETs), also known as carcinoid tumors of the extrahepatic
      biliary tree, are extremely rare malignancies and account for 0.2% to 2% of all
      carcinoids of the gastrointestinal tract. The most common sites include NET in
      the common bile duct (CBD), followed by the perihilar region, cystic duct, and
      common hepatic duct (CHD). A review of the literature showed only eight cases of
      NETs of the cystic duct and we, hereby, present the ninth case of NET of the
      cystic duct in a 50-year-old woman. This was discovered incidentally after she
      underwent a laparoscopic cholecystectomy for her symptomatic gallbladder stones.
      The etiology is not known but the NETs are thought to arise from argentaffin
      cells (Kulchitsky cells) in the gastrointestinal tract or respiratory tract. It
      is possible that the rarity of these in this region may be explained by the very
      limited number of Kulchitsky cells there. Most of the patients are clinically
      asymptomatic, and the diagnosis is mostly made during surgery performed for other
      indications. Therefore, early recognition should be sought by differentiating the
      primary duct carcinoma of the bile or the cystic duct, if suspected or shown on
      the imaging studies because of the different therapeutic options and prognosis.

PMID- 29226046
TI  - The Economic Impacts of Chronic Illness on Households of Patients in Ile-Ife,
      South-Western Nigeria.
AB  - Introduction Chronic illnesses are slowly becoming more prevalent worldwide. The
      implications and ramifications of these illnesses vary and affect not only the
      patient but the entire household in many ways. This research focuses on the
      economic implications of this category of illnesses on the entire household. The
      aim is to determine the economic implications of chronic illnesses on households
      of patients in selected health facilities in Ile-Ife, Nigeria, and to elucidate
      the various coping strategies applied by households in low and middle income
      countries (LMICs) to keep up with these economic implications. Methods This study
      features a descriptive cross-sectional survey design with a total sample of 443.
      The target population consists of individuals with chronic diseases in selected
      health care facilities in Ile-Ife.  Results The mean household monthly incomes
      before and after illness episodes were found to be $335.84 and $318.01,
      respectively. The mean direct cost of chronic illness was $137.72 with about 79%
      (n=350) of the respondents spending more than 10% of the monthly household income
      on health. The indirect costs of illness were a loss of productivity of 18.9% and
      5.1% for patients and caregivers, respectively. A large percentage of the
      respondents resorted to borrowing (44.7%; n=198), while another 5.0% (n=22) sold
      assets, and 8.6% (n=38) had access to health insurance in order to cope with the
      economic impacts of the illness. Conclusion The study showed that chronic
      illnesses imposed high and catastrophic cost burdens on patients and their
      households. The lack of effective coping strategies points at the need for
      policymakers to improve access to specialized care and increase coverage of
      formal health insurance so as to ameliorate the significant economic impacts that
      chronic illnesses have on entire households.

PMID- 29226048
TI  - Retroperitoneal Pseudoaneurysm Mimicking Ureteral Calculus: Pitfalls in
      Diagnosis.
AB  - Arterial aneurysms (AA) can be classified as true aneurysms, characterized by the
      persistence of all three layers of the arterial wall with progressive dilation
      and wall thinning; arterial pseudoaneurysms (APAs) are characterized by a tear in
      the vessel wall and a periarterial hematoma formation. They could occur due to a
      visceral, retroperitoneal, or peripheral origin. Most AA/APA are usually found
      incidentally, and it is imperative to be vigilant in order to diagnose and manage
      them due to their potentially life-threatening complications. We present a case
      of a 35-year-old woman presenting with right-sided abdominal pain mimicking renal
      colic with an initial misdiagnosis of ureteral calculus. Post-cystoscopy, a
      misdiagnosis was confirmed, and subsequently, the patient had a right
      retroperitoneal mass excision. The histopathology report concluded the calcified
      retroperitoneal mass to be pseudoaneurysm. Such pitfalls in diagnosis are
      essential to be shared with the larger medical community for increased vigilance
      and optimal management of pseudoaneurysms.

PMID- 29226047
TI  - A Preliminary Investigation of General and Technique-specific Assessments for the
      Evaluation of Laparoscopic Technical Skills.
AB  - Background  Both general and technique-specific assessments of technical skill
      have been validated in surgical education. The purpose of this study was to
      assess the correlation between the objective structured assessment of technical
      skills (OSATS) and the global operative assessment of laparoscopic skills (GOALS)
      rating scales using a high-fidelity porcine laparoscopic cholecystectomy model.
      Methods Post-graduate year-one general surgery and urology residents (n=14)
      performed a live laparoscopic porcine cholecystectomy. Trained surgeons rated
      their performance using OSATS and GOALS assessment scales. Results Pearson's
      correlation coefficient between OSATS and GOALS was 0.96 for overall scores. It
      ranged from 0.78 - 0.89 for domains that overlapped between the two scales.
      Conclusion There is a very high correlation between OSATS and GOALS. This implies
      that they likely measure similar constructs and that either may be used for
      summative-type assessments of trainee skill. However, further investigation is
      needed to determine if technique-specific assessments may provide more useful
      feedback in formative evaluation.

PMID- 29226049
TI  - Unresectable Undifferentiated Embryonal Sarcoma of the Liver in an Adult Male
      Treated with Chemotherapy and Orthotopic Liver Transplantation.
AB  - Undifferentiated embryonal sarcoma of the liver (UESL) is a malignancy of
      mesenchymal origin observed predominantly in the pediatric population and very
      rarely in adults. We describe the case of a 21-year-old male who presented with
      acute onset of right upper quadrant pain and distention. Physical examination of
      the patient revealed right upper quadrant tenderness with the lower border of the
      liver palpable, 4 cm below the right costal margin. Laboratory tests performed on
      admission showed that the patient's liver function tests, urinalysis, complete
      blood count, and basic metabolic panel were within reference range. The levels of
      viral hepatitis and tumor serum markers were all within normal limits except for
      an elevated level of cancer antigen (CA) 19-9. Magnetic resonance imaging (MRI)
      and a computerized tomography (CT) scan showed two well-circumscribed lesions in
      the right lobe. The biopsy of the lesion showed UESL. The patient was started on
      chemotherapy. On his fifth cycle of chemotherapy, the patient was offered
      orthotopic liver transplantation (OLT). The patient underwent a successful OLT.
      There were no postoperative complications. Increased survival time and prevention
      of the recurrence of USEL can be achieved by surgical resection of the tumor
      combined with adjuvant and neoadjuvant chemotherapy. For unresectable tumors, OLT
      with chemotherapy can be a potential cure in younger patients.

PMID- 29226050
TI  - Determinants of Computed Tomography Head Scan Ordering for Patients with Low-Risk
      Headache in the Emergency Department.
AB  - Background Many specialty societies have found that neuroimaging in headache is a
      low-value intervention for benign presentations. This study describes factors
      that influence Emergency Room (ER) physicians' adherence to Choosing Wisely (CW)
      recommendations for low-risk headache patients presenting to Calgary's Emergency
      Departments (EDs). Emergency medicine has yet to address imaging in headache as a
      CW topic; however, this study may inform that decision. Methods Data were
      retrospectively collected for all patients presenting to Calgary EDs with
      headaches from April 1, 2014 to March 31, 2016. Patients were deemed low-risk by
      virtue of discharge home from the ED, age < 50, and no lumbar puncture (LP),
      trauma, neurology, or neurosurgery consult or red flags on history. The primary
      outcome was computed tomography (CT) ordering rates with an eye to medical doctor
      (MD) practice variation. Patient, physician, and environmental factors were
      analyzed to compare patients who did and did not receive a CT. Results Two
      thousand seven hundred and thirty-four headache patients met the eligibility
      criteria. A total of 117 Calgary ER physicians were included, all of whom had
      seen 10 or more headache patients over the study period. Physician practice
      variation was vast, with a mean ordering rate of 38.0% and a range of 0% to 95%
      (M = 39.0%, IQR = 21.0%). CTs were ordered more often in males than females
      (39.9%; 34.1%; p = 0.002) and in patients presenting during the day and evening
      (38.1%; 39.0%) compared to the night (29.7%; p < 0.001). Patients were divided
      into quartiles by age, with the oldest group (41.6 - 50 years) receiving
      significantly more head CTs (45.1%) than the other quartiles (34.9%; 34.9%;
      27.5%; p < 0.001). Longer triage-to-discharge times were associated with an
      increase in CT ordering rates (12% for < 2.95 hours; 35% for > 4 hour wait; p <
      0.001). Lastly, patients who did not have a CT were more likely to revisit the ED
      within seven days compared to those who did (6.9% vs 4.0%; p = 0.003), but their
      seven-day admission rate was unaffected (0.6% in the group that got CTs and 0.3%
      in the group that did not get a CT). Time to assessment, the day of the week,
      physician gender, years of experience, and training program did not influence CT
      ordering practices. Conclusion To our knowledge, this is the first study to
      assess how patient, physician, and environmental factors relate to the use of CT
      scans in low-risk headaches presenting to the ED. CW guidelines are not optimally
      adhered to, and the findings in this study findings may inspire new ideas for
      maximizing the judicious use of healthcare resources.

PMID- 29226051
TI  - Cadaveric Study for Intraoral Needle Access to the Infratemporal Fossa:
      Application to Posterior Superior Alveolar Nerve Block Technique.
AB  - The posterior superior alveolar (PSA) nerve block is, from an anatomical
      perspective, challenging because the mandibular ramus and the zygomatic process
      of the maxilla can interfere with the course of the needle. Dentists empirically
      know that shifting the patient's mandible to the ipsilateral side can improve
      visibility and accessibility for such blocks. This cadaveric study aimed to
      establish anatomical evidence for the ipsilateral mandible shifting used in the
      PSA. The distance between the lateral most bulging point of the alveolar part of
      the maxilla and ipsilateral anterior border of the ramus of the mandible ranged
      from 1.4 to 6.9 mm with a mean of 4.3 +/- 1.6 mm. This result supports the
      empirical technique of shifting the mandible ipsilaterally for PSA nerve block.

PMID- 29226052
TI  - Developing a Continuous Quality Improvement Assessment Using a Patient-Centered
      Approach in Optimizing Systemic Lupus Erythematosus Disease Control.
AB  - Systemic lupus erythematosus (SLE) is a multi-organ, autoimmune disease in which
      patients lose self-tolerance and develop immune complexes which deposit
      systemically causing multi-organ damage and inflammation. Patients often
      experience unpredictable flares of symptoms with poorly identified triggers.
      Literature suggests exogenous exposures may contribute to flares in symptoms. An
      online pilot survey was marketed globally through social media to self-reported
      SLE patients with the goal to identify specific subpopulations who are
      susceptible to disease state changes based on analyzed exogenous factors. The
      pilot survey was promoted for two weeks, 80 respondents fully completed the
      survey and were included in statistical analysis. Descriptive statistical
      analysis was performed on de-identified patient surveys and compared to previous
      literature studies reporting known or theorized triggers in the SLE disease
      state. The pilot survey identified similar exogenous triggers compared to
      previous literature, including antibiotics, increasing beef intake, and metal
      implants. The goal of the pilot survey is to utilize similar questions to develop
      a detailed internet-based patient interactive form that can be edited and time
      stamped as a method to promote continuous quality improvement assessments. The
      ultimate objective of the platform is to interact with SLE patients from across
      the globe longitudinally to optimize disease control and improve quality of care
      by allowing them to avoid harmful triggers.

PMID- 29226053
TI  - Compression Stockings and Pressure Ulcers: Case Series of a Neglected Issue.
AB  - Pressure ulcers develop in patients who endure long periods of immobilization,
      often caused by conditions such as musculoskeletal and neurological diseases.
      Pressure ulcers adversely affect the patient and increase caregiver burden and
      healthcare costs. Typical sites for these ulcers include the sacrum, trochanters,
      and heels; they also occur on the nape of the neck, penis, nostrils, helix of the
      ear, and upper back. Compression stockings are commonly used to prevent and stop
      the progression of venous disorders, including deep vein thrombosis, but their
      role in the development of pressure ulcers is not well known. We describe three
      case reports of pressure ulcer development due to prolonged application of
      compression stockings. In each case, the nursing staff who were primarily
      responsible for the prevention of pressure ulcers applied the stockings
      continuously without any intermittent relief. Moreover, the stockings did not
      include manufacturer instructions, such as recommended exposure times and
      applications. We recommend that nursing staff be trained in pressure relief and
      prevention of pressure ulcers, including rare occurrences, and that manufacturers
      give detailed guidance regarding the safe use of compression stockings.

PMID- 29226054
TI  - Reversible Broad-Spectrum Control of Selective Reflections of Chiral Nematic
      Phases by Closed-/Open-Type Axially Chiral Azo Dopants.
AB  - Invited for this month's cover picture is the groups of Professor Hirotsugu
      Kikuchi and Dr. Yasushi Okumura at the Institute for Materials Chemistry and
      Engineering at Kyushu University (Japan). External dynamic control of molecular
      self-organized superstructures with unique features has been researched, as these
      structures are applicable to chiral molecular devices. The cover picture shows
      photocontrol of selective reflection color that originated from the self
      organized helical structure of chiral nematic liquid crystals (N*LCs) using
      closed-/open-type dopants. The drastic structure changes of the dopants by light
      stimuli enable reversible broad-spectrum control of selective reflections of
      N*LCs with opposite helical sign. Read the full text of the Full Paper at
      10.1002/open.201700121.

PMID- 29226055
TI  - Fluorescence Sensing with Cellulose-Based Materials.
AB  - Cellulose-based materials functionalized with fluorescence sensors are highly
      topical and are employed in many areas of functional materials, including the
      sensing of heavy-metal ions and anions as well as being widely used as chemical
      sensors and tools for environmental applications. In this Review, we cover recent
      progress in the development of cellulose-based fluorescence sensors as parts of
      membranes and nanoscale materials for the detection of biological analytes. We
      believe that this Review will be of interest to chemists, chemical engineers, and
      biochemists in the sensor community as well as researchers working with
      biological material systems.

PMID- 29226056
TI  - beta-Deuterium Isotope Effects on Firefly Luciferase Bioluminescence.
AB  - A 5,5-d2 -luciferin was prepared to measure isotope effects on reactions of two
      intermediates in firefly bioluminescence: emission by oxyluciferin and
      elimination of a putative luciferyl adenylate hydroperoxide to dehydroluciferin.
      A negligible isotope effect on bioluminescence provides further support for the
      belief that the emitting species is the keto-phenolate of oxyluciferin and rules
      out its excited-state tautomerization, one potential contribution to a
      bioluminescence quantum yield less than unity. A small isotope effect on
      dehydroluciferin formation supports a single-electron-transfer mechanism for
      reaction of the luciferyl adenylate enolate with oxygen to form the hydroperoxide
      or dehydroluciferin. Partitioning between the dioxetanone intermediate (en route
      to oxyluciferin) and dehydroluciferin is determined, not by the fate of the
      hydroperoxide, but by that of the radical formed from luciferyl adenylate, and
      the kinetic isotope effect (KIE) reflects H-atom abstraction by superoxide.

PMID- 29226057
TI  - Photocatalytic Overall Water Splitting over MIL-125(Ti) upon CoPi and Pt Co
      catalyst Deposition.
AB  - Photocatalytic overall water splitting is realized by taking advantage of the
      semiconductive and porous properties of MIL-125(Ti). CoPi and Pt are deposited
      into MIL-125(Ti) in two steps. The co-catalysts CoPi and Pt not only act as
      reactive sites for oxygen and hydrogen evolution, respectively, but also improve
      the photogenerated charge separation efficiency. The above conclusions are
      supported by the photoelectrical and photophysical results.

PMID- 29226058
TI  - Towards Fingermark Dating: A Raman Spectroscopy Proof-of-Concept Study.
AB  - Fingermarks have, for a long time, been vital in the forensic community for the
      identification of individuals, and a possibility to non-destructively date the
      fingermarks would of course be beneficial. Raman spectroscopy is, herein,
      evaluated for the purpose of estimating the age of fingermarks deposits. Well
      resolved spectra were non-destructively acquired to reveal spectral uniqueness,
      resembling those of epidermis, and several molecular markers were identified that
      showed different decay kinetics: carotenoids > squalene > unsaturated fatty acids
      > proteins. The degradation rates were accelerated, less pronounced for proteins,
      when samples were stored under ambient light conditions, likely owing to photo
      oxidation. It is hypothesized that fibrous proteins are present and that
      oxidation of amino acid side chains can be observed both through Raman and
      fluorescence spectroscopy. Clearly, Raman spectroscopy is a useful technique to
      non-destructively study the aging processes of fingermarks.

PMID- 29226059
TI  - Reversible Broad-Spectrum Control of Selective Reflections of Chiral Nematic
      Phases by Closed-/Open-Type Axially Chiral Azo Dopants.
AB  - We demonstrate reversible RGB-color photocontrol of a chiral nematic liquid
      crystal (N*LC) by using newly synthesized closed- and open-type chiral dopants.
      The photoswitching elements in the dopants are azobenzene units on axially chiral
      binaphthyl cores. Owing to cis-trans photoisomerization of the azobenzene units,
      both closed- and open-type compounds showed higher solubility, larger helical
      twisting power (HTP), and larger changes in HTP than conventional chiral dopants
      in host LCs. Thus, even at very low dopant concentrations, we successfully
      controlled the chirality of the induced helical structure of the N*LCs.
      Consequently, the N*LCs reflected right- and left-handed circularly polarized
      light (CPL) under a light stimulus. In the N*LCs with closed-type chiral dopants,
      the RGB-color reflection was reversibly controlled within several seconds.
      Interestingly, the open-type chiral dopant reversibly inverted CPL with opposite
      handedness in the near and short-wave IR regions. These novel materials are
      expected to realize new applications and perspectives in color information and
      similar technologies.

PMID- 29226060
TI  - Stable Europium(III) Complexes with Short Linkers for Site-Specific Labeling of
      Biomolecules.
AB  - In this study, two new terpyridine-based EuIII complexes were synthesized, the
      structures of which were optimized for luminescence resonance energy-transfer
      (LRET) experiments. The complexes showed high quantum yields (32 %); a single
      long lifetime (1.25 ms), which was not influenced by coupling to protein; very
      high stability in the presence of chelators such as ethylenediamine-N,N,N',N'
      tetraacetate and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic
      acid; and no interaction with cofactors such as adenosine triphosphate and
      guanosine triphosphate. A special feature is the short length of the linker
      between the EuIII ion and the maleimide or hydrazide function, which allows for
      site-specific coupling of cysteine mutants or unnatural keto amino acids. As a
      consequence, the new complexes appear particularly suited for accurate distance
      measurements in biomolecules by LRET.

PMID- 29226061
TI  - Shaping Polyyne Rods by Using an Electric Field.
AB  - When a homogenous electric field is applied to polyynes (C10 and C20)
      perpendicular to their long axis, they bend to form an arch. The height of the
      arch is proportional to the intensity of the electric field. The direction of the
      bend and its magnitude depend on the electronic nature (donor/acceptor) of the
      substituents at the termini of the polyyne. The driving force for the formation
      of the arch is the dipole moment produced in the system parallel to the electric
      field. This dipole moment stems from the substituents and from additional
      polarization by the field. The bend of the linear polyyne fits a parabolic
      distortion. According to mechanical engineering analysis, this results from a
      moment that operates at the two end zones of the polyynes, in accordance with the
      natural bond order (NBO) charge distribution. It is shown that solutions relevant
      to beam deflection due to a central load or a uniformly distributed load are not
      satisfactory. Various parameters, such as the dipole moment and the height of the
      arch, are better correlated with sigma than with sigma+ or sigma-. Application of
      the electric field to more complex systems enables the sculpting of interesting
      nanoshapes.

PMID- 29226062
TI  - Interactions of Protonated Guanidine and Guanidine Derivatives with Multiply
      Deprotonated RNA Probed by Electrospray Ionization and Collisionally Activated
      Dissociation.
AB  - Interactions of ribonucleic acid (RNA) with guanidine and guanidine derivatives
      are important features in RNA-protein and RNA-drug binding. Here we have
      investigated noncovalently bound complexes of an 8-nucleotide RNA and six
      different ligands, all of which have a guanidinium moiety, by using electrospray
      ionization (ESI) and collisionally activated dissociation (CAD) mass spectrometry
      (MS). The order of complex stability correlated almost linearly with the number
      of ligand atoms that can potentially be involved in hydrogen-bond or salt-bridge
      interactions with the RNA, but not with the proton affinity of the ligands.
      However, ligand dissociation of the complex ions in CAD was generally accompanied
      by proton transfer from ligand to RNA, which indicated conversion of salt-bridge
      into hydrogen-bond interactions. The relative stabilities and dissociation
      pathways of [RNA+m L-n H] n- complexes with different stoichiometries (m=1-5) and
      net charge (n= 2-5) revealed both specific and unspecific ligand binding to the
      RNA.

PMID- 29226064
TI  - An exploratory study of illegal gamblers in Hong Kong.
AB  - This study investigates the nature and behaviour of illegal gamblers in Hong
      Kong. A face-to-face street survey of 512 gamblers was conducted in Hong Kong
      between September and December 2015 with supplementary convenience sampling
      allowing for analysis of a total sample of 103 illegal gamblers. 56% of illegal
      gamblers recorded results consistent with this study's definition of 'excessive
      gambling' [i.e. moderate risk and problem gamblers under the Problem Gambling
      Severity Index (PGSI)]. 81% of surveyed illegal gamblers were male, 77% were aged
      between 30 and 49 and 67% were in blue collar occupations. Illegal gamblers bet
      more frequently on both legal and illegal games than their legal counterparts and
      spent more when they did bet. While this research did not indicate the direction
      of causality between illegal and excessive gambling, international work (de Bruin
      et al. in verslingerd aan meer dan een spel: Een onderzoek naar de aard en omvang
      van kansspelproblematiek in Nederland, WODC/CVO, Utrecht,
      http://www.lexandgaming.eu/nl/wp-content/uploads/2015/01/Verslingerd-aan-meer-dan
      een-spel.pdf, 2005; Binde in What are the most harmful forms of gambling?
      Analysing problem gambling prevalence surveys,
      http://www.utbildning.gu.se/digitalAssets/1327/1327132_cefos-wp12.pdf, 2011)
      suggests that excessive gamblers are drawn to illegal gambling. Reform could
      allow excessive gambling by illegal gamblers to be better addressed and initial
      work suggests some financial benefits to Hong Kong.

PMID- 29226063
TI  - Advances in antimicrobial photodynamic inactivation at the nanoscale.
AB  - The alarming worldwide increase in antibiotic resistance amongst microbial
      pathogens necessitates a search for new antimicrobial techniques, which will not
      be affected by, or indeed cause resistance themselves. Light-mediated
      photoinactivation is one such technique that takes advantage of the whole
      spectrum of light to destroy a broad spectrum of pathogens. Many of these
      photoinactivation techniques rely on the participation of a diverse range of
      nanoparticles and nanostructures that have dimensions very similar to the
      wavelength of light. Photodynamic inactivation relies on the photochemical
      production of singlet oxygen from photosensitizing dyes (type II pathway) that
      can benefit remarkably from formulation in nanoparticle-based drug delivery
      vehicles. Fullerenes are a closed-cage carbon allotrope nanoparticle with a high
      absorption coefficient and triplet yield. Their photochemistry is highly
      dependent on microenvironment, and can be type II in organic solvents and type I
      (hydroxyl radicals) in a biological milieu. Titanium dioxide nanoparticles act as
      a large band-gap semiconductor that can carry out photo-induced electron transfer
      under ultraviolet A light and can also produce reactive oxygen species that kill
      microbial cells. We discuss some recent studies in which quite remarkable
      potentiation of microbial killing (up to six logs) can be obtained by the
      addition of simple inorganic salts such as the non-toxic sodium/potassium iodide,
      bromide, nitrite, and even the toxic sodium azide. Interesting mechanistic
      insights were obtained to explain this increased killing.

PMID- 29226066
TI  - Instrumental Variable Analyses in Pharmacoepidemiology: What Target Trials Do We
      Emulate?
AB  - Purpose of review: When leveraging observational data to estimate treatment
      effects, it is useful to explicitly specify the "target trial" the investigators
      aspire to emulate. One concern is whether a proposed analysis plan can address
      the realities of the differences between the available non-randomized
      observational study and the target trial. When large or unknown sources of
      unmeasured confounding are suspected, investigators might consider turning to
      instrumental variable (IV) methods. Of course, the interpretation and
      appropriateness of IV analyses need to be considered carefully. The purpose of
      this review is to summarize recent methodologic advancements in how
      epidemiologists weigh the validity of an IV analysis and to place these
      methodologic advancements in the context of the feasible target trial's protocol
      components. Recent findings: There have been increased development and
      application of tools for sensitivity analyses, falsification strategies, and the
      identification of previously overlooked problems with IV analyses as applied in
      pharmacoepidemiology. Many of these recent insights can be seen as articulating
      restrictions on or tradeoffs between the types of target trials that can be
      validly emulated when using a classical IV analysis. Summary: Putting classical
      IV methods in the context of target trials underscores the importance of recent
      methodologic developments and, more generally, when and how an IV analysis would
      be appropriate. We see that some tradeoffs in defining the target trials are
      unavoidable, that some tradeoffs may be offset or explored via sensitivity
      analyses, and that this serves as a framework for scientific discourse regarding
      IV and non-IV results emulating potentially different trials with different
      tradeoffs.

PMID- 29226065
TI  - Challenges and Opportunities in Studying the Epidemiology of Ovarian Cancer
      Subtypes.
AB  - Purpose of review: Only recently has it become clear that epithelial ovarian
      cancer (EOC) is comprised of such distinct histotypes--with different cells of
      origin, morphology, molecular features, epidemiologic factors, clinical features,
      and survival patterns-that they can be thought of as different diseases sharing
      an anatomical location. Herein, we review opportunities and challenges in
      studying EOC heterogeneity. Recent findings: The 2014 World Health Organization
      diagnostic guidelines incorporate accumulated evidence that high- and low-grade
      serous tumors have different underlying pathogenesis, and that, on the basis of
      shared molecular features, most high grade tumors, including some previously
      classified as endometrioid, are now considered to be high-grade serous. At the
      same time, several studies have reported that high-grade serous EOC, which is the
      most common histotype, is itself made up of reproducible subtypes discernable by
      gene expression patterns. Summary: These major advances in understanding set the
      stage for a new era of research on EOC risk and clinical outcomes with the
      potential to reduce morbidity and mortality. We highlight the need for
      multidisciplinary studies with pathology review using the current guidelines,
      further molecular characterization of the histotypes and subtypes, inclusion of
      women of diverse racial/ethnic and socioeconomic backgrounds, and updated
      epidemiologic and clinical data relevant to current generations of women at risk
      of EOC.

PMID- 29226067
TI  - Recent Developments in Mendelian Randomization Studies.
AB  - Purpose of Review: Mendelian randomization (MR) is a strategy for evaluating
      causality in observational epidemiological studies. MR exploits the fact that
      genotypes are not generally susceptible to reverse causation and confounding, due
      to their fixed nature and Mendel's First and Second Laws of Inheritance. MR has
      the potential to provide information on causality in many situations where
      randomized controlled trials are not possible, but the results of MR studies must
      be interpreted carefully to avoid drawing erroneous conclusions. Recent Findings:
      In this review, we outline the principles behind MR, as well as assumptions and
      limitations of the method. Extensions to the basic approach are discussed,
      including two-sample MR, bidirectional MR, two-step MR, multivariable MR, and
      factorial MR. We also consider some new applications and recent developments in
      the methodology, including its ability to inform drug development, automation of
      the method using tools such as MR-Base, and phenome-wide and hypothesis-free MR.
      Summary: In conjunction with the growing availability of large-scale genomic
      databases, higher level of automation and increased robustness of the methods, MR
      promises to be a valuable strategy to examine causality in complex
      biological/omics networks, inform drug development and prioritize intervention
      targets for disease prevention in the future.

PMID- 29226068
TI  - Human Brucellosis and Adverse Pregnancy Outcomes.
AB  - Purpose of Review: Brucellosis is a neglected, zoonotic disease of nearly
      worldwide distribution. Despite brucellosis being recognized as a reproductive
      disease in animals, it has been historically known as a flu-like illness in
      humans with little or no significant role in maternal or newborn health. This
      review focuses on what is currently known relative to the epidemiology of
      brucellosis in human pregnancy as well as new insights of placental immunology.
      Recent Findings: New evidence suggests that maternal infection poses a
      significant risk factor for adverse pregnancy outcomes including increased risk
      for miscarriage during the first and second trimester of gestation, preterm
      delivery, and vertical transmission to the fetus. Adverse pregnancy outcomes were
      not associated with any specific clinical sign. However, prompt diagnosis and
      treatment significantly decreased the risk of miscarriage or any other adverse
      effect. Summary: Brucellosis during pregnancy should be considered a significant
      risk factor for adverse pregnancy outcomes in humans. The identification of the
      mechanism behind bacterial tropism should prove powerful for the development of
      new countermeasures to prevent these detrimental effects. Increased awareness
      concerning brucellosis in pregnant women, its transmission, and prevention
      measures should be considered as a pressing need.

PMID- 29226070
TI  - Economic burden of community-acquired pneumonia among elderly patients: a
      Japanese perspective.
AB  - Background: This study aimed to estimate the economic burden of community
      acquired pneumonia (CAP) among elderly patients in Japan. In addition, the study
      evaluated the relationship between total treatment cost and CAP risk factors.
      Methods: An administrative database was searched for elderly patients (>= 65
      years old) who had pneumonia (ICD-10 code: J12-J18) and an antibiotic
      prescription between 1 June 2014 and 31 May 2015. The all-cause total healthcare
      costs of outpatient and inpatient CAP episodes were calculated. Results: This
      study evaluated data from 29,619 patients with CAP who experienced 14,450
      outpatient CAP episodes and/or 20,314 inpatient CAP episodes. The mean ages were
      77.5 +/- 8.0 years and 81.5 +/- 8.2 years among the outpatient and inpatient
      groups, respectively. The median treatment costs were US$346 (interquartile
      range: $195-551) per outpatient episode and US$4851 (interquartile range: $3313
      7669) per inpatient episode. More severe cases had increased treatment costs at
      the treating hospitals. Male sex, diabetes, chronic obstructive pulmonary
      disease, and liver dysfunction were associated with increased total treatment
      costs, while dementia, dialysis, and rheumatism were associated with high costs
      of treating a CAP episode. Conclusions: The economic burden of CAP might be
      decreased by reducing the number of hospitalizations for mild CAP and the
      incidence of severe CAP. Therefore, preventative care (e.g. oral hygiene or
      pneumococcus vaccination) is recommended for patients with related risk factors,
      such as male sex, older age, diabetes, chronic obstructive pulmonary disease,
      liver dysfunction, rheumatism, dementia, or dialysis.

PMID- 29226069
TI  - Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies.
AB  - Purpose of Review: Sleep habits, sleep physiology, and sleep disorders change
      with increasing age. However, there is a longstanding debate regarding whether
      older adults need sleep to maintain health and daily functioning (reduced-sleep
      need view). An alternative possibility is that all older adults need sleep, but
      that many older adults have lost the ability to obtain restorative sleep (reduced
      sleep-ability view). Prior research using behavioral and polysomnography outcomes
      has not definitively disentangled the reduced-sleep-need and reduced-sleep
      ability views. Therefore, this review examines the neuroimaging literature to
      determine whether age-related changes in sleep cause-or are caused by-age-related
      changes in brain structure, function, and pathology. Recent Findings: In middle
      aged and older adults, poorer sleep quality, greater nighttime hypoxia, and
      shorter sleep duration related to cortical thinning in frontal regions implicated
      in slow wave generation, in frontoparietal networks implicated in cognitive
      control, and in hippocampal regions implicated in memory consolidation.
      Furthermore, poor sleep quality was associated with higher amyloid burden and
      decreased connectivity in the default mode network, a network that is disrupted
      in the pathway to Alzheimer's disease. Summary: All adults need sleep, but
      cortical thinning and amyloidal deposition with advancing age may weaken the
      brain's ability to produce restorative sleep. Therefore, sleep in older adults
      may not always support identical functions for physical, mental, and cognitive
      health as in young adults.

PMID- 29226071
TI  - Structural enzymology comparisons of multifunctional enzyme, type-1 (MFE1): the
      flexibility of its dehydrogenase part.
AB  - : Multifunctional enzyme, type-1 (MFE1) is a monomeric enzyme with a 2E-enoyl-CoA
      hydratase and a 3S-hydroxyacyl-CoA dehydrogenase (HAD) active site. Enzyme
      kinetic data of rat peroxisomal MFE1 show that the catalytic efficiencies for
      converting the short-chain substrate 2E-butenoyl-CoA into acetoacetyl-CoA are
      much lower when compared with those of the homologous monofunctional enzymes. The
      mode of binding of acetoacetyl-CoA (to the hydratase active site) and the very
      similar mode of binding of NAD + and NADH (to the HAD part) are described and
      compared with those of their monofunctional counterparts. Structural comparisons
      suggest that the conformational flexibility of the HAD and hydratase parts of
      MFE1 are correlated. The possible importance of the conformational flexibility of
      MFE1 for its biocatalytic properties is discussed. Database: Structural data are
      available in PDB database under the accession number 5MGB.

PMID- 29226072
TI  - A thermal gradient modulates the oxidative metabolism and growth of human
      keratinocytes.
AB  - During their spatial and differentiative progression, keratinocytes face a
      thermal gradient, from 37  degrees C in the proliferating basal layer to 32 
      degrees C found in skin surface. In our study, we hypothesized that this
      difference in temperature must be balanced by increasing the heat produced during
      respiratory activity. We demonstrated that at 33  degrees C human primary
      keratinocytes and HaCaT cells raised mitochondrial energy metabolism, but not
      glycolytic activity. At 33  degrees C, the increased mitochondrial ATP synthesis
      was associated with a strong induction of the modulator of the respiratory chain
      estrogen receptor beta, whereas uncoupling protein 1 expression was not changed.
      The enhanced mitochondrial oxidative metabolism was accompanied by a remarkable
      reduction in proliferation. These results suggest that environmental temperature
      can modulate the energy metabolism and proliferation of human keratinocytes.

PMID- 29226073
TI  - Cloning of canine Ku80 and its localization and accumulation at DNA damage sites.
AB  - Molecularly targeted therapies have high specificity and significant cancer
      killing effect. However, their antitumor effect might be greatly diminished by
      variation in even a single amino acid in the target site, as it occurs, for
      example, as a consequence of SNPs. Increasing evidence suggests that the DNA
      repair protein Ku80 is an attractive target molecule for the development of next
      generation radiosensitizers for human cancers. However, the localization, post
      translational modifications (PTMs), and complex formation of Ku80 have not been
      elucidated in canines. In this study, for the first time, we cloned, sequenced,
      and characterized canine Ku80 cDNA. Our data show that canine Ku80 localizes in
      the nuclei of interphase cells and is quickly recruited at laser-induced double
      strand break sites. Comparative analysis shows that canine Ku80 had only 82.3%
      amino acid identity with the homologous human protein, while the nuclear
      localization signal (NLS) in human and canine Ku80 is evolutionarily conserved.
      Notably, some predicted PTM sites, including one acetylation site and one
      sumoylation site within the NLS, are conserved in the two species. These findings
      suggest that the spatial and temporal regulation of Ku80 might be conserved in
      humans and canines. However, our data indicate that the expression of Ku80 is
      considerably lower in the canine cell lines examined than in human cell lines.
      These important findings might be useful to better understand the mechanism of
      the Ku80-dependent DNA repair and for the development of potential next
      generation radiosensitizers targeting common targets in human and canine cancers.

PMID- 29226074
TI  - Characterization of auxiliary iron-sulfur clusters in a radical S
      adenosylmethionine enzyme PqqE from Methylobacterium extorquens AM1.
AB  - PqqE is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the initial
      reaction of pyrroloquinoline quinone (PQQ) biosynthesis. PqqE belongs to the
      SPASM (subtilosin/PQQ/anaerobic sulfatase/mycofactocin maturating enzymes)
      subfamily of the radical SAM superfamily and contains multiple Fe-S clusters. To
      characterize the Fe-S clusters in PqqE from Methylobacterium extorquens AM1, Cys
      residues conserved in the N-terminal signature motif (CX 3 CX 2C) and the C
      terminal seven-cysteine motif (CX 9-15 GX 4 CX n CX 2 CX 5 CX 3 CX n C; n = an
      unspecified number) were individually or simultaneously mutated into Ser.
      Biochemical and Mossbauer spectral analyses of as-purified and reconstituted
      mutant enzymes confirmed the presence of three Fe-S clusters in PqqE: one [4Fe
      4S]2+ cluster at the N-terminal region that is essential for the reductive
      homolytic cleavage of SAM into methionine and 5'-deoxyadenosyl radical, and one
      each [4Fe-4S]2+ and [2Fe-2S]2+ auxiliary clusters in the C-terminal SPASM domain,
      which are assumed to serve for electron transfer between the buried active site
      and the protein surface. The presence of [2Fe-2S]2+ cluster is a novel finding
      for radical SAM enzyme belonging to the SPASM subfamily. Moreover, we found
      uncommon ligation of the auxiliary [4Fe-4S]2+ cluster with sulfur atoms of three
      Cys residues and a carboxyl oxygen atom of a conserved Asp residue.

PMID- 29226075
TI  - Prediction of target genes for miR-140-5p in pulmonary arterial hypertension
      using bioinformatics methods.
AB  - The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary
      arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat.
      Identification of target genes for miR-140-5p with bioinformatics analysis may
      reveal new pathways and connections in PAH. This study aimed to explore
      downstream target genes and relevant signaling pathways regulated by miR-140-5p
      to provide theoretical evidences for further researches on role of miR-140-5p in
      PAH. Multiple downstream target genes and upstream transcription factors (TFs) of
      miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis
      indicated that downstream target genes of miR-140-5p were enriched in many
      biological processes, such as biological regulation, signal transduction,
      response to chemical stimulus, stem cell proliferation, cell surface receptor
      signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway
      analysis found that downstream target genes were mainly located in Notch, TGF
      beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network,
      the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4,
      JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly
      reviewing published literature, we found that 23 target genes and seven signaling
      pathways were truly inhibited by miR-140-5p in various tissues or cells; most of
      these verified targets were in accordance with our present prediction. Other
      predicted targets still need further verification in vivo and in vitro.

PMID- 29226076
TI  - Increasing the length and hydrophobicity of the C-terminal sequence of
      transthyretin strengthens its binding affinity to retinol binding protein.
AB  - Transthyretin (TTR) is a transporter for thyroid hormone (TH) and retinol, the
      latter via binding with retinol binding protein (RBP). Both the N-terminal and C
      terminal regions of the TTR subunit are located in close proximity to the central
      binding channel for ligands. During the evolution of vertebrates, these regions
      changed in length and hydropathy. The changes in the N-terminal sequence were
      demonstrated to affect the binding affinities for THs and RBP. Here, the effects
      of changes in the C-terminal sequence were determined. Three chimeric TTRs,
      namely pigC/huTTR (human TTR with the C-terminal sequence changed to that of Sus
      scrofa TTR), xenoN/pigC/huTTR (human TTR with the N-terminal and C-terminal
      sequences changed to those of Xenopus laevis and S. scrofa, respectively), and
      pigC/crocTTR (Crocodylus porosus TTR with the C-terminal sequence changed to that
      of S. scrofa TTR), were constructed and their binding affinities for human RBP
      were determined at low TTR/RBP molar ratio using chemiluminescence
      immunoblotting. The binding dissociation constant (Kd) values of pigC/huTTR,
      xenoN/pigC/huTTR and pigC/crocTTR were 3.20 +/- 0.35, 1.53 +/- 0.38 and 0.31 +/-
      0.04 MUm, respectively, and the Kd values of human and C. porosus TTR were 4.92
      +/- 0.68 and 1.42 +/- 0.45 MUm, respectively. These results demonstrate chimeric
      TTRs bound RBP with a higher strength than wild-type TTRs, and the changes in the
      C-terminal sequence of TTR had a positive effect on its binding affinity for RBP.
      In addition, changes to the N-terminal and C-terminal sequences showed comparable
      effects on the binding affinity.

PMID- 29226077
TI  - Leptin-induced migration and angiogenesis in rheumatoid arthritis is mediated by
      reactive oxygen species.
AB  - Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting the
      joints. In this study, we investigated the role of the pro-angiogenic factor
      leptin in regulating reactive oxygen species (ROS) to promote cell migration and
      angiogenesis in RA. We showed that leptin triggered RA fibroblast-like
      synoviocyte (FLS) migration by increased ROS expression. Additionally, leptin
      enhanced human umbilical vein endothelial cell (HUVEC) tube formation in a
      ROS/hypoxia-inducible factor-1alpha-dependent manner, accompanied by increased
      production of vascular endothelial growth factor and interleukin (IL)-6. We also
      revealed that antagonists of tumor necrosis factor, IL-6 and IL-1beta down
      regulated ROS production of RA FLS induced by leptin, which subsequently
      attenuated RA FLS migration and HUVEC tube formation. These findings demonstrated
      that leptin might play an important role in RA FLS migration and HUVEC
      angiogenesis.

PMID- 29226078
TI  - Identification and in silico structural analysis of Gallus gallus protein
      arginine methyltransferase 4 (PRMT4).
AB  - Protein arginine methyltransferase 4 (PRMT4) is an essential epigenetic regulator
      of fundamental and conserved processes during vertebrate development, such as
      pluripotency and differentiation. Surprisingly, PRMT4 homologs have been
      identified in nearly all vertebrate classes except the avian genome. This raises
      the possibility that in birds PRMT4 functions are taken over by other PRMT family
      members. Here, we reveal the existence of a bona fide PRMT4 homolog in the
      chicken, Gallus gallus. Using a biochemical approach, we initially purified a
      putative chicken PRMT4 protein and thus provided the first evidence for the
      presence of an endogenous PRMT4-specific enzymatic activity toward histone H3
      arginine 17 (H3R17) in avian cells. We then isolated a G. gallus PRMT4 (ggPRMT4)
      transcript encompassing the complete open reading frame. Recombinant ggPRMT4
      possesses intrinsic methyltransferase activity toward H3R17. CRISPR/Cas9-mediated
      deletion of ggPRMT4 demonstrated that the transcript identified here encodes
      avian PRMT4. Combining protein-protein docking and homology modeling based on
      published crystal structures of murine PRMT4, we found a strong structural
      similarity of the catalytic core domain between chicken and mammalian PRMT4.
      Strikingly, in silico structural comparison of the N-terminal Pleckstrin homology
      (PH) domain of avian and murine PRMT4 identified strictly conserved amino acids
      that are involved in an interaction interface toward the catalytic core domain,
      facilitating for the first time a prediction of the relative spatial arrangement
      of these two domains. Our novel findings are particularly exciting in light of
      the essential function of the PH domain in substrate recognition and methylation
      by PRMT4.

PMID- 29226079
TI  - Alteration of glucocorticoid receptors and exacerbation of inflammation during
      lytic cytomegalovirus infection in THP-1 cells.
AB  - Cytomegalovirus (CMV) infection is associated with glucocorticoid resistance in
      ulcerative colitis (UC) and may exacerbate the disease course. However, the
      underlying pathogenicity remains unclear. The aim of this study was to explore
      possible underlying mechanisms during CMV latency and lytic infection in the
      human mononuclear cell line THP-1. Latent and activated CMV infection cell models
      were established. We performed real-time PCR and western blotting to examine
      changes in glucocorticoid receptors (GRs) during CMV latency and activation. Pro
      inflammatory and anti-inflammatory cytokines were detected by ELISA. After UV
      inactivated CMV infection, GRs and cytokines were also examined. The expression
      of GRs was elevated in the reactivation group. An increased ratio of GR
      beta/alpha and phosphorylation of GRalpha in the CMV reactivation group may
      explain refractory response to steroids. During CMV lytic infection, pro
      inflammatory cytokines IL-6 and TNF-alpha increased remarkably and anti
      inflammatory cytokine IL-5 decreased, which may exacerbate UC. GR and cytokines
      were unchanged in the UV-inactivated CMV infection group. Changes in the number
      and function of GRs may account for glucocorticoid resistance in CMV
      reactivation. The imbalance of pro- and anti-inflammatory cytokines may be
      related to severe inflammation.

PMID- 29226080
TI  - FAD influx enhances neuronal differentiation of human neural stem cells by
      facilitating nuclear localization of LSD1.
AB  - Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor
      in energy production and plays an important role in cell survival. More recently,
      riboflavin deficiency has been linked to developmental disorders, but its role in
      stem cell differentiation remains unclear. Here, we show that FAD treatment,
      using DMSO as a solvent, enabled an increase in the amount of intracellular FAD
      and promoted neuronal differentiation of human neural stem cells (NSCs) derived
      not only from fetal brain, but also from induced pluripotent stem cells.
      Depression of FAD-dependent histone demethylase, lysine-specific demethylase-1
      (LSD1), prevented FAD-induced neuronal differentiation. Furthermore, FAD influx
      facilitated nuclear localization of LSD1 and its enzymatic activity. Together,
      these findings led us to propose that FAD contributes to proper neuronal
      production from NSCs in the human fetal brain during development.

PMID- 29226081
TI  - The SWEET gene family in Hevea brasiliensis - its evolution and expression
      compared with four other plant species.
AB  - SWEET proteins play an indispensable role as a sugar efflux transporter in plant
      development and stress responses. The SWEET genes have previously been
      characterized in several plants. Here, we present a comprehensive analysis of
      this gene family in the rubber tree, Hevea brasiliensis. There are 36 members of
      the SWEET gene family in this species, making it one of the largest families in
      plant genomes sequenced so far. Structure and phylogeny analyses of these genes
      in Hevea and in other species demonstrated broad evolutionary conservation. RNA
      seq analyses revealed that SWEET2, 16, and 17 might represent the main
      evolutionary direction of SWEET genes in plants. Our results in Hevea suggested
      the involvement of HbSWEET1a, 2e, 2f, and 3b in phloem loading, HbSWEET10a and
      16b in laticifer sugar transport, and HbSWEET9a in nectary-specific sugar
      transport. Parallel studies of RNA-seq analyses extended to three other plant
      species (Manihot esculenta, Populus trichocarpa, and Arabidopsis thaliana)
      produced findings which implicated MeSWEET10a, 3a, and 15b in M. esculenta
      storage root development, and the involvement of PtSWEET16b and PtSWEET16d in P.
      trichocarpa xylem development. RT-qPCR results further revealed that HbSWEET10a,
      16b, and 1a play important roles in phloem sugar transport. The results from this
      study provide a foundation not only for further investigation into the
      functionality of the SWEET gene family in Hevea, especially in its sugar
      transport for latex production, but also for related studies of this gene family
      in the plant kingdom.

PMID- 29226082
TI  - The novel mitochondria localization of influenza A virus NS1 visualized by FlAsH
      labeling.
AB  - The nonstructural protein 1 (NS1) of the influenza A virus (IAV) is a
      multifunctional protein that counteracts host cell antiviral responses and
      inhibits host cell pre-mRNA processing. NS1 contains two nuclear localization
      signals that facilitate NS1 shuttling between cytoplasm and nucleus. In this
      study, we initially observed the novel mitochondria localization of NS1 in a
      subset of transfected cells. We then further monitored the localization dynamics
      of the NS1 protein in live cells infected with IAV expressing NS1 with insertion
      of a tetracysteine-tag. The resulting mutant virus showed similar levels of
      infectivity and expression pattern of NS1 to those of wild-type IAV. Pulse
      labeling using a biarsenical compound (fluorescein arsenical hairpin binder)
      allowed us to visualize the dynamic subcellular distribution of NS1 real time. We
      detected NS1 in mitochondria at a very early infection time point [1.5 h
      postinfection (hpi)] and observed the formation of a granular structure pattern
      in the nucleus at 4 hpi. This is the first identification of the novel
      mitochondria localization of NS1. The possible role of NS1 at an early infection
      time point is discussed.

PMID- 29226083
TI  - Effects of O-methylated (-)-epigallocatechin gallate (EGCG) on LPS-induced
      osteoclastogenesis, bone resorption, and alveolar bone loss in mice.
AB  - (-)-Epigallocatechin-3-O-gallate (EGCG), present in green tea, exhibits
      antioxidant and antiallergy effects. EGCG3"Me, a 3-O-methylated derivative of
      EGCG, has been reported to show similar biological functions; the inhibitory
      activity of EGCG3"Me in a mouse allergy model was more potent than that of EGCG,
      probably due to the efficiency of absorption from the intestine. However, the
      functional potency of these EGCGs is controversial in each disease model. We
      previously observed that EGCG suppressed inflammatory bone resorption and
      prevented alveolar bone loss in a mouse model of periodontosis. In this study, we
      examined the role of EGCG3"Me in bone resorption using a mouse model of
      periodontitis. Lipopolysaccharide (LPS)-induced osteoclast formation was
      suppressed by adding EGCG3"Me to cocultures of osteoblasts and bone marrow cells,
      and LPS-induced bone resorption was also inhibited by EGCG3"Me in calvarial organ
      cultures. EGCG3"Me acted on osteoblasts and suppressed prostaglandin E (PGE)
      production, which is critical for inflammatory bone resorption, by inhibiting the
      expression of COX-2 and mPGES-1, key enzymes for PGE synthesis. In osteoclast
      precursor macrophages, EGCG3"Me suppressed RANKL-dependent differentiation into
      mature osteoclasts. In a mouse model of periodontitis, LPS-induced bone
      resorption was suppressed by EGCG3"Me in organ culture of mouse alveolar bone,
      and the alveolar bone loss was further attenuated by the treatment of EGCG3"Me in
      the lower gingiva in vivo. EGCG3"Me may be a potential natural compound for the
      protection of inflammatory bone loss in periodontitis.

PMID- 29226084
TI  - N-glycosylation and expression in human tissues of the orphan GPR61 receptor.
AB  - A number of members of the G protein-coupled receptor class of cell surface
      receptors are 'orphans' with no known endogenous ligand. One of these orphan
      receptors is GPR61; there are little data about its expression in human cells and
      tissues. In this study, we investigated the post-translational modification of
      GPR61 by N-glycosylation at an identified consensus N-glycosylation site (N12)
      and the impact of this modification upon the subcellular expression of the
      protein. The N-glycosylation inhibitor tunicamycin reduced the apparent molecular
      weight of immunoreactivity associated with myc-tagged GPR61 by 1-2 kDa, which was
      comparable to the evident molecular weight of the myc-tagged N12S GPR61 mutant
      with disrupted consensus N-glycosylation site. Analysis of GPR61 expression
      demonstrated that tunicamycin treatment reduced considerably heterologous
      expression of GPR61 in the cell membrane despite the N12S GPR61 mutant being
      readily expressed at the cell surface. These results demonstrate that GPR61 is
      subject to N-glycosylation but suggest this is not a prerequisite for cell
      surface expression, although N-glycosylation of other proteins may be important
      for cell membrane expression of GPR61. Expression of GPR61 protein was
      demonstrated at the cellular level in human hippocampus and human peripheral
      blood mononuclear cells. In the latter, there was a significantly higher
      expression of GPR61 in the Th17 cell subset in comparison with resting CD4+
      cells, which may point toward a potential role for the GPR61 receptor in
      autoimmune diseases. This is the first report that GPR61 protein is subject to
      post-translational modification and is expressed in immune cell subsets and the
      hippocampus. These findings will help guide studies to investigate the function
      of GPR61.

PMID- 29226085
TI  - Cysteine and histidine residues are involved in Escherichia coli Tn21 MerE
      methylmercury transport.
AB  - Bacterial resistance to mercury compounds (mercurials) is mediated by proteins
      encoded by mercury resistance (mer) operons. Six merE variants with site-directed
      mutations were constructed to investigate the roles of the cysteine and histidine
      residues in MerE protein during mercurial transport. By comparison of mercurial
      uptake by the cell with intact and/or variant MerE, we showed that the cysteine
      pair in the first transmembrane domain was critical for the transport of both
      Hg(II) and CH 3Hg(I). Also, the histidine residue located near to the cysteine
      pair was critical for Hg(II) transport, whereas the histidine residue located on
      the periplasmic side was critical for CH 3Hg(I) transport. Thus, enhanced
      mercurial uptake mediated by MerE may be a promising strategy for the design of
      new biomass for use in the bioremediation of mercurials in the environment.

PMID- 29226086
TI  - Fibroblasts promote the collective invasion of ameloblastoma tumor cells in a 3D
      coculture model.
AB  - Ameloblastoma is a benign tumor of the odontogenic epithelium with several
      histological subtypes. All subtypes of ameloblastoma contain abundant stroma; the
      tumor cells invade collectively into the surrounding tissues without losing
      intratumor cell attachments. However, the molecular mechanisms mediating
      ameloblastoma invasion remain unclear. Here, we evaluated the functional
      significance of the interactions between ameloblastoma tumor cells and stromal
      fibroblasts on collective cellular invasion using a three-dimensional cultivation
      method, double-layered collagen gel hemisphere (DL-CGH) culture. The AM-1
      plexiform and AM-3 follicular human ameloblastoma cell lines and HFF-2 human
      fibroblasts were labeled with GFP and DsRed, respectively. Collective cellular
      invasion of ameloblastoma cells was assessed in the presence or absence of
      fibroblasts. Notably, without fibroblasts, AM-1 cells formed sharp, plexiform
      like invasive processes, whereas AM-3 cells formed a series of blunt processes
      often observed during collective migration. In comparison, under the cocultures
      with HFF-2 fibroblasts, AM-3 cells formed tuft-like invasive processes and
      collectively invaded into outer layer more than that observed with AM-1 cells.
      Moreover, HFF-2 fibroblasts localized to the tips of the invasive tumor
      processes. These findings suggest that tumor-associated cells assist tumor cell
      invasion. Microscopic analysis of sectioned three-dimensional cultures revealed
      that AM-3/HFF-2 hemispheres were histologically similar to follicular
      ameloblastoma tumor samples. Therefore, our findings suggest that ameloblastoma
      subtypes exhibit distinct invasion patterns and that fibroblasts promote
      collective tumor invasion in follicular ameloblastoma.

PMID- 29226087
TI  - Multiple-cumulative probabilities used to cluster and visualize transcriptomes.
AB  - Analysis of gene expression data by clustering and visualizing played a central
      role in obtaining biological knowledge. Here, we used Pearson's correlation
      coefficient of multiple-cumulative probabilities (PCC-MCP) of genes to define the
      similarity of gene expression behaviors. To answer the challenge of the high
      dimensional MCPs, we used icc-cluster, a clustering algorithm that obtained
      solutions by iterating clustering centers, with PCC-MCP to group genes. We then
      used t-statistic stochastic neighbor embedding (t-SNE) of KC-data to generate
      optimal maps for clusters of MCP (t-SNE-MCP-O maps). From the analysis of several
      transcriptome data sets, we demonstrated clear advantages for using icc-cluster
      with PCC-MCP over commonly used clustering methods. t-SNE-MCP-O was also shown to
      give clearly projecting boundaries for clusters of PCC-MCP, which made the
      relationships between clusters easy to visualize and understand.

PMID- 29226088
TI  - A chimeric HS4 insulator-scaffold attachment region enhances transgene expression
      in transfected Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells are one of the most commonly used expression
      systems for the production of recombinant proteins but low levels of transgene
      expression and transgene silencing are frequently encountered. Epigenetic
      regulatory elements such as the chicken beta-globin locus control region
      hypersensitive site 4 (HS4) and scaffold/matrix attachment regions (S/MARs) have
      positive effects on transgene expression. In this study, a chimeric HS4-SAR was
      cloned upstream or downstream of an enhanced green fluorescent protein (eGFP)
      expression cassette in a eukaryotic vector, and the resulting vectors were
      transfected into CHO cells. eGFP was detected by flow cytometry. Real-time
      quantitative PCR (qPCR) was used to determine copy numbers of the stably
      transfected cells. And fluorescence in situ hybridization (FISH) was used to
      detect the status of vector in the host cell chromosome. The results showed that
      HS4-SAR positioned downstream of the expression cassette could enhance eGFP
      expression by 4.83-fold compared with the control vector. There may not be a
      relationship between transgene copy number and gene expression level. HS4-SAR did
      not appear to alter the integration of the transgene into the host cell
      chromosome or its position in the chromosome. We found a synthetic chimeric HS4
      SAR positively increased transgene expression in CHO cells.

PMID- 29226090
TI  - Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation
      enhances anti-PD1 efficacy against osteosarcoma cancer.
AB  - Myeloid derived suppressor cells (MDSC) are very important in tumor immune
      evasion and they dramatically increased in peripheral blood of patients with
      osteosarcoma cancer. The association between MDSC and various cytokines has been
      studied in the peripheral blood. However, little is known about the mechanism
      drawing MDSC into tumor parenchyma. This study was to analyze the correlation
      between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model
      and its effect on the immunotherapy. MDSC were isolated from the blood and
      parenchyma and analyzed in the osteosarcoma tumor model. IL-18 levels were
      detected by enzyme-linked immunosorbent assay (ELISA) assay, real-time PCR,
      western blot and flow cytometry. Moreover, combination treatment with IL-18
      inhibition and anti-PD1 was conducted to assess the therapeutic effects of IL-18
      blockade. Results showed MDSC levels had a positive correlation with IL-18,
      suggesting IL-18 may attract MDSC into the parenchyma. IL-18 gene and protein
      expression significantly increased in blood and tumor lysates of tumor-bearing
      mice. Anti-IL-18 treatment significantly decreased G-MDSC and M-MDSC in the
      peripheral blood and tumor. Furthermore, combination therapy decreased the tumor
      burden and increased CD4+ and CD8+ T cell infiltration, as well as the production
      of interferon gamma (IFNgamma) and granzyme B. Our study revealed a possible
      correlation between MDSC subsets and IL-18 inducing MDSC migration into the tumor
      tissue, in addition to provide the potential target to enhance the efficacy of
      immunotherapy in patients with osteosarcoma.

PMID- 29226089
TI  - Oncolytic adenoviruses as a therapeutic approach for osteosarcoma: A new hope.
AB  - Osteosarcoma is the most common bone cancer among those with non-hematological
      origin and affects mainly pediatric patients. In the last 50 years, refinements
      in surgical procedures, as well as the introduction of aggressive neoadjuvant and
      adjuvant chemotherapeutic cocktails, have increased to nearly 70% the survival
      rate of these patients. Despite the initial therapeutic progress the fight
      against osteosarcoma has not substantially improved during the last three
      decades, and almost 30% of the patients do not respond or recur after the
      standard treatment. For this group there is an urgent need to implement new
      therapeutic approaches. Oncolytic adenoviruses are conditionally replicative
      viruses engineered to selectively replicate in and kill tumor cells, while
      remaining quiescent in healthy cells. In the last years there have been multiple
      preclinical and clinical studies using these viruses as therapeutic agents in the
      treatment of a broad range of cancers, including osteosarcoma. In this review, we
      summarize some of the most relevant published literature about the use of
      oncolytic adenoviruses to treat human osteosarcoma tumors in subcutaneous,
      orthotopic and metastatic mouse models. In conclusion, up to date the preclinical
      studies with oncolytic adenoviruses have demonstrated that are safe and
      efficacious against local and metastatic osteosarcoma. Knowledge arising from
      phase I/II clinical trials with oncolytic adenoviruses in other tumors have shown
      the potential of viruses to awake the patient's own immune system generating a
      response against the tumor. Generating osteosarcoma immune-competent adenoviruses
      friendly models will allow to better understand this potential. Future clinical
      trials with oncolytic adenoviruses for osteosarcoma tumors are warranted.

PMID- 29226091
TI  - Successful treatment of multicompartmental cerebral ventriculitis caused by
      Acinetobacter baumanii.
AB  - We present a case report of a 58-year- old woman with subarachnoid haemorrhage
      complicated by non-communicating hydrocephalus. During the course of her
      neurosurgical management, she developed external-ventricular drain associated
      ventriculitis which in turn was complicated by lack of communication between
      third and fourth ventricles. The causative organism was a fully-sensitive
      Acinetobacter baumanii, a nosocomial pathogen often associated with complicated
      treatment regimens and poor outcomes. This patient was successfully managed by a
      multi-disciplinary team involving neurosurgeons, neuroradiologists and infection
      specialists. Patient made a full recovery following double CSF diversion and
      intravenous plus intrathecal antimicrobial therapy.

PMID- 29226092
TI  - Aggressive surgical management of adenocarcinoma of the rete testis.
AB  - Adenocarcinoma of the rete testis is a rare and aggressive malignancy arising
      from the epididymal epithelium. We present a case of a 66-year-old male who
      presented with left testis mass. Histopathological analysis of orchiectomy
      specimen was consistent with adenocarcinoma of the rete testis. Subsequent
      retroperitoneal lymph node dissection revealed metastatic disease not detected on
      preoperative PET-CT. Prior reports have suggested poor response rates to both
      systemic chemotherapy and radiation therapy. Aggressive surgical management of
      the retroperitoneum should be considered even in clinically node-negative
      patients given the paucity of other effective treatment regimens.

PMID- 29226093
TI  - Complete biochemical response after stereotactic ablative radiotherapy of an
      isolated prostate cancer pelvic soft tissue recurrence detected by 18F-DCFPyL
      PET/CT.

PMID- 29226094
TI  - Epstein Barr virus-associated smooth muscle tumour (EBV-SMT) of the urinary
      bladder.

PMID- 29226095
TI  - Atypical hemolytic-uremic syndrome due to complement factor I mutation.
AB  - Atypical hemolytic-uremic syndrome (aHUS) is a rare disease of complement
      dysregulation leading to thrombotic microangiopathy (TMA). Renal involvement and
      progression to end-stage renal disease are common in untreated patients. We
      report a 52-year-old female patient who presented with severe acute kidney
      injury, microangiopathic hemolytic anemia, and thrombocytopenia. She was managed
      with steroid, plasma exchange, and dialysis. Kidney biopsy shows TMA and renal
      cortical necrosis. Genetic analysis reveals heterozygous complement factor I
      (CFI) mutation. Eculizumab was initiated after 3 mo of presentation, continued
      for 9 mo, and stopped because of sustained hematologic remission, steady renal
      function, and cost issues. Despite this, the patient continued to be in
      hematologic remission and showed signs of renal recovery, and peritoneal dialysis
      was stopped 32 mo after initiation. We report a case of aHUS due to CFI mutation,
      which, to the best of our knowledge, has not been reported before in Saudi
      Arabia. Our case illustrates the challenges related to the diagnosis and
      management of this condition, in which a high index of suspicion and prompt
      treatment are usually necessary.

PMID- 29226096
TI  - Feasibility of two active case finding approaches for detection of tuberculosis
      in Bandung City, Indonesia.
AB  - Setting: A community health clinic catchment area in the eastern part of Bandung
      City, Indonesia. Objective: To evaluate the feasibility of two different
      screening interventions using community health workers (CHWs) in detecting
      tuberculosis (TB) cases. Design: This was a feasibility study of 1) house-to
      house TB symptom screening of five randomly selected 'neighbourhoods' in the
      catchment area, and 2) selected screening of household contacts of TB index
      patients and their neighbouring households. Acceptability was assessed through
      focus group discussions with key stakeholders. Results: Of 5100 individuals
      screened in randomly selected neighbourhoods, 48 (0.9%) reported symptoms, of
      whom 38 provided sputum samples; no positive TB was found. No TB cases were found
      among the 88 household contacts or the 423 neighbourhood contacts. With training,
      regular support and supervision from research staff and local community health
      centre staff, CHWs were able to undertake screening effectively, and almost all
      householders were willing to participate. Conclusion: The use of CHWs for TB
      screening could be integrated into routine practice relatively easily in
      Indonesia. The effectiveness of this would need further exploration, particularly
      with the use of improved diagnostics such as chest X-ray and sputum culture.

PMID- 29226098
TI  - Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naive
      Patients by Intra-PBMC Nested Viral RNA PCR.
AB  - Background and Aims: Occult HCV infections (OCIs) include IgG antibody
      seronegative cryptogenic (COCIs), as well as seropositive secondary naive
      (SNOCIs) and experienced (SEOCIs) cases. We used peripheral-blood-mononuclear
      cell (PBMC)-PCR to evaluate COCIs and SNOCIs prevalence, serum HCV spontaneous
      disappearance (SCSD) in naive cirrhotics and non-cirrhotics, intra-PBMC HCV-RNA
      strands in relation to cirrhosis density in naive non-viremia cases, and HCV-RNA
      seroconversion after 1 year of solitary naive intra-PBMC infection. Methods: The
      anti-HCV IgG antibody-positive naive-patients (n = 785) were classified into
      viremic (n = 673) and non-viremic [n = 112, including non-cirrhotics (n = 55) and
      cirrhotics (n = 57)], and 62 controls without evidence of HCV-infection. Controls
      and post-HCV non-viremia cases (n = 62+112 = 174) were submitted to hepatic
      Fibroscan-Elastography evaluation. All subjects (n = 847) were screened for intra
      PBMC HCV-RNA sense and antisense strands by nested-PCR. Results: Naive-OCI cases
      (4.84%) that were diagnosed by PBMC-PCR significantly raised the total numbers of
      HCV-infection to 714 (p = 0.01). The percent positivity of SNOCIs (34.82%) was
      significantly higher than for asymptomatic-COCIs (3.125%, p = 0.0001). Comparing
      PBMC-PCR with single-step-reverse-transcription (SRT)-PCR for identification of
      SCSD in naive IgG antibody-positive non-viremia patients (n = 112) revealed a
      decline in SCSD prevalence by PBMC-PCR (from 14.27% to 9.3%), regardless of
      presence of hepatic cirrhosis (p = 0.03). SCSD was found to be higher by PBMC-PCR
      in non-cirrhotics compared to cirrhotics (p = 0.0001), with an insignificant
      difference when using SRT-PCR (p = 0.45). Intra-PBMC HCV-RNA infection was
      significantly more frequent in cirrhotics compared to both non-cirrhotics and
      controls (p < 0.0005). An increased hepatic fibrosis density was recognized in
      intra-PBMC HCV-RNA infection with sense (p = 0.0001) or antisense strand (p =
      0.003). HCV-RNA seroconversion was associated with intra-PBMC infection when both
      sense and antisense strands were detected (p = 0.047). Conclusions: Intracellular
      HCV-RNA evaluation is crucial for diagnosing OCIs and addressing relapse
      probability.

PMID- 29226099
TI  - Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected
      Patients Taking Proton Pump Inhibitors.
AB  - Background and Aims: Direct-acting antiviral (DAA) therapy is the cornerstone of
      the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV,
      predicted by the attainment of a sustained virologic response (SVR) 12 weeks
      following DAA therapy, is the goal of this treatment. Interestingly, recent
      studies have reported the possible association between HCV-infected patients with
      DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of
      achieving SVR. This meta-analysis was conducted to summarize all available data
      and to estimate this potential association. Methods: Comprehensive literature
      review was conducted by first searching the Medline and Embase databases through
      March 2017 to identify all studies that investigated the safety and efficacy of
      DAAs in patients with HCV infection taking PPIs versus those without PPIs.
      Adjusted point estimates from each study were combined by the generic inverse
      variance method of DerSimonian and Laird. Results: Nine cohort studies with
      32,684 participants met the eligibility criteria and were included in the meta
      analysis. The use of PPIs concomitant with DAAs among HCV-infected patients was
      associated with lower odds of achieving SVR compared with non-PPI users (pooled
      odds ratio (OR): 0.74, 95% confidence interval (CI): 0.63-0.88, I2 = 24%).
      Subgroup analysis addressed the association between PPIs use and SVR12
      demonstrated the association of PPI users showing lower odds of achieving SVR12
      compared with those with no use of PPIs (pooled OR: 0.68, 95% CI: 0.51-0.9, I2 =
      33%). Conclusions: This study demonstrated a significantly increased risk of
      failure to achieve SVR in HCV-infected patients taking DAA with PPIs compared to
      non-PPI users. Providers should consider whether PPI therapy is indicated for
      patients and withdraw of PPI therapy in the absence of indications, especially
      while on DAA therapy.

PMID- 29226097
TI  - Guideline of Prevention and Treatment for Chronic Hepatitis B (2015 Update).

PMID- 29226100
TI  - Clinical Food Addiction Is Not Associated with Development of Metabolic
      Complications in Liver Transplant Recipients.
AB  - Background and Aims: Given the increased risk of post-transplant metabolic
      syndrome (PTMS; defined by hypertension, diabetes mellitus and hyperlipidemia),
      we aimed to identify the potential role of food addiction in the development of
      metabolic complications in the post-liver transplant population. Methods:
      Inclusion criteria included adult liver transplant recipients followed at our
      institution between June 2016 and November 2016. Participants were administered a
      demographic survey as well as the Yale Food Assessment Scale 2.0, a 35-item
      questionnaire used to assess frequency of food addiction in accordance with the
      DSM-V guidelines of substance use disorders. Demographic and clinical data were
      collected. Results: Our study included 236 liver transplant recipients (139
      males, 97 females). The median (interquartile range [IQR]) BMI of participants
      was 26.8 kg/m2 (24.2, 30.4), and median (IQR) time since transplantation was 50.9
      months (19.6, 119.8). The prevalence rates of hypertension, hypercholesterolemia
      and diabetes mellitus were 54.7%, 25.0% and 27.1%, respectively. Twelve
      participants (5.1%) were found to have a diagnosis of food addiction. A diagnosis
      of food misuse was made in 94 (39.8%) of the transplant recipients. Conclusions:
      Our findings are consistent with prior data that indicate high prevalence of
      metabolic complications among liver transplant recipients. Food addiction was not
      predictive of metabolic complications within this population. Nevertheless, we
      found that this population was at high risk of demonstrating symptoms of food
      misuse, and they were not likely to appreciate the risks of pathologic patterns
      of eating. Given the increasing risk of cardiovascular morbidity and mortality in
      this population, efforts should be made to identify risk factors for the
      development of PTMS.

PMID- 29226101
TI  - Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review.
AB  - Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing
      chronic liver disease in 170 million people worldwide. Recent data has identified
      HCV infection as a risk factor for subclinical and clinical cardiovascular
      disease (CVD), but these data have been mixed and whether HCV is an independent
      risk factor for development of CVD remains controversial. In this review, we
      present the literature regarding the association of HCV with subclinical and
      clinical CVD and the possible underlying mechanisms leading to increased CVD
      among those infected with HCV. HCV infection leads to increased CVD via direct
      and indirect mechanisms with chronic inflammation, endothelial dysfunction and
      direct invasion of the arterial wall cited as possible mechanisms. Our review
      showed that HCV infection, particularly chronic HCV infection, appears to lead to
      increased subclinical CVD most consistently and potentially also to increased
      clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore,
      the majority of studies evaluating the impact of HCV therapy on CVD morbidity and
      mortality showed an improvement in subclinical and clinical CVD endpoints in
      patients who were successfully treated and achieved sustained viral suppression.
      These results are of particular interest following the development of new direct
      antiviral agents which have made HCV eradication simple and feasible for many
      more patients globally, and in doing so may possibly reduce CVD morbidity and
      mortality in those with chronic HCV infection.

PMID- 29226102
TI  - Timing of Hepatitis C Virus Treatment in Liver Transplant Candidates in the Era
      of Direct-acting Antiviral Agents.
AB  - Chronic hepatitis C virus (HCV) infection remains the leading indication for
      liver transplantation (LT) in the United States. While most patients with chronic
      HCV infection remain asymptomatic, up to one-third develop progressive liver
      disease resulting in cirrhosis. LT is often the only curative treatment once
      significant hepatic decompensation develops. However, antiviral therapy for HCV
      infection has advanced markedly in the past 5 years with the discovery and
      approval of direct-acting antiviral agents. These new regimens are well
      tolerated, of short duration and highly effective, unlike the traditional
      treatment with pegylated-interferon and ribavirin. As achieving sustained
      virological response becomes increasingly attainable for a majority of HCV
      infected patients, concerns have been raised regarding the optimal timing of
      treatment for HCV infection in the setting of end-stage liver disease and during
      the peri-transplant period. On one hand, HCV treatment may improve hepatic
      function and negate the need for LT in some, which is crucial given the scarcity
      of donor organs and mortality on the waiting list in certain regions. On the
      other hand, HCV treatment may result in lowering the priority for LT without
      improving quality of life, thereby delaying potentially curative LT surgery. This
      review evaluates the evidence supporting the use of direct-acting antiviral
      agents in the period before and following LT.

PMID- 29226103
TI  - Clinical Application of Vibration Controlled Transient Elastography in Patients
      with Chronic Hepatitis B.
AB  - Evaluation of the extent and progression of liver fibrosis and cirrhosis is of
      critical importance in the management and prognosis of patients with chronic
      hepatitis B. Due to the limitation of liver biopsy, non-invasive methods,
      especially liver stiffness measurement (LSM) by vibration controlled transient
      elastography, have been developed and widely applied for liver fibrosis
      assessment. LSM aims to reduce, but not to substitute, the need for liver biopsy
      for fibrosis/cirrhosis diagnosis. While LSM may have potential utility in
      monitoring treatment response, its applications in prediction of liver
      complications in terms of portal hypertension and esophageal varices, as well as
      disease prognosis, have been gradually validated. Here, we review the latest
      clinical applications of LSM in patients with chronic hepatitis B.

PMID- 29226104
TI  - Hepatitis E: A Literature Review.
AB  - Hepatitis E is the fifth known form of human viral hepatitis. Although not very
      common in our clinical practice, the incidence in Western countries is
      increasing. Infection with the hepatitis E virus (HEV) may be related to acute
      illness, liver failure, chronic hepatitis and cirrhosis. HEV itself is an RNA
      virus, with eight described genotypes (HEV 1-8), four of which more commonly
      affect humans and have, thus, been better studied. Besides liver manifestations,
      genotype 3 is also related to extra-hepatic manifestations, such as neurological,
      renal and rheumatological. Evolution to chronic disease occurs especially in
      patients who underwent transplantation, have hematological malignancies requiring
      chemotherapy, or have infection with the human immunodeficiency virus. The
      diagnosis may be difficult because of the low availability of tests and due to
      low sensibility and specificity. The acute form of illness does not have to be
      treated, but the chronic one does. We present here a literature review of
      hepatitis E and the relation between chronic hepatitis E and transplantation.

PMID- 29226105
TI  - Non-alcoholic Fatty Liver Disease: A Clinical Update.
AB  - Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic
      liver disease in developed countries because of the obesity epidemic. The disease
      increases liver-related morbidity and mortality, and often increases the risk for
      other comorbidities, such as type 2 diabetes and cardiovascular disease. Insulin
      resistance related to metabolic syndrome is the main pathogenic trigger that, in
      association with adverse genetic, humoral, hormonal and lifestyle factors,
      precipitates development of NAFLD. Biochemical markers and radiological imaging,
      along with liver biopsy in selected cases, help in diagnosis and prognostication.
      Intense lifestyle changes aiming at weight loss are the main therapeutic
      intervention to manage cases. Insulin sensitizers, antioxidants, lipid lowering
      agents, incretin-based drugs, weight loss medications, bariatric surgery and
      liver transplantation may be necessary for management in some cases along with
      lifestyle measures. This review summarizes the latest evidence on the
      epidemiology, natural history, pathogenesis, diagnosis and management of NAFLD.

PMID- 29226106
TI  - Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do?
AB  - Elevated liver enzymes are a common scenario encountered by physicians in
      clinical practice. For many physicians, however, evaluation of such a problem in
      patients presenting with no symptoms can be challenging. Evidence supporting a
      standardized approach to evaluation is lacking. Although alterations of liver
      enzymes could be a normal physiological phenomenon in certain cases, it may also
      reflect potential liver injury in others, necessitating its further assessment
      and management. In this article, we provide a guide to primary care clinicians to
      interpret abnormal elevation of liver enzymes in asymptomatic patients using a
      step-wise algorithm. Adopting a schematic approach that classifies enzyme
      alterations on the basis of pattern (hepatocellular, cholestatic and isolated
      hyperbilirubinemia), we review an approach to abnormal alteration of liver
      enzymes within each section, the most common causes of enzyme alteration, and
      suggest initial investigations.

PMID- 29226108
TI  - Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline
      Phosphatase.
AB  - Alcoholic hepatitis (AH) is an acute inflammatory liver disease with poor
      prognosis. Infections in AH are difficult to detect and contribute to short-term
      mortality. Intrahepatic cholestasis and elevated alkaline phosphatase levels are
      also associated with worse outcomes. This report describes an uncommon
      presentation of severe AH.

PMID- 29226107
TI  - Cholangitis: Diagnosis, Treatment and Prognosis.
AB  - Cholangitis is a serious life-threatening situation affecting the hepatobiliary
      system. This review provides an update regarding the clinical and pathological
      features of various forms of cholangitis. A comprehensive search was performed in
      the PubMed, Scopus, and Web of Knowledge databases. It was found that the
      etiology and pathogenesis of cholangitis are heterogeneous. Cholangitis can be
      categorized as primary sclerosing (PSC), secondary (acute) cholangitis, and a
      recently characterized form, known as IgG4-associated cholangitis (IAC). Roles of
      genetic and acquired factors have been noted in development of various forms of
      cholangitis. PSC commonly follows a chronic and progressive course that may
      terminate in hepatobiliary neoplasms. In particular, PSC commonly has been
      associated with inflammatory bowel disease. Bacterial infections are known as the
      most common cause for AC. On the other hand, IAC has been commonly encountered
      along with pancreatitis. Imaging evaluation of the hepatobiliary system has
      emerged as a crucial tool in the management of cholangitis. Endoscopic retrograde
      cholangiography, magnetic resonance cholangiopancreatography and endoscopic
      ultrasonography comprise three of the modalities that are frequently exploited as
      both diagnostic and therapeutic tools. Biliary drainage procedures using these
      methods is necessary for controlling the progression of cholangitis. Promising
      results have been reported for the role of antibiotic treatment in management of
      AC and PSC; however, immunosuppressive drugs have also rendered clinical
      responses in IAC. With respect to the high rate of complications, surgical
      interventions in patients with cholangitis are generally restricted to those
      patients in whom other therapeutic approaches have failed.

PMID- 29226110
TI  - Comparison Effect of Promethazine/Dexamethasone and Metoclopramide /Dexamethasone
      on Postoperative Nausea and Vomiting after Laparascopic Gastric Placation: A
      Randomized Clinical Trial.
AB  - Background: Laparoscopic gastric plication (LGP) is a technique in the
      restrictive category of bariatric procedures that reduces the gastric volume and
      increases intragastric pressure. Nausea and vomiting are the most common
      complications after this procedure. The goal of this research is to compare the
      combined effect of promethazine/dexamethasone versus Metoclopramide/
      dexamethasone on the prevention of nausea and vomiting after LGP. Methods: In
      recovery, the patients were divided into two groups, the Metoclopramide group
      which was given Metoclopramide 10 mg plus dexamethasone 4 mg/8 hours intravenous
      for 48 hours, and the promethazine group which was given promethazine 50 mg /12
      hours, intramuscular for the first 24 hours and then promethazine 25 mg/12 hours
      for the next 24 hours plus dexamethasone 4 mg/8 hours intravenous for 48 hours.
      The frequency of nausea and vomiting, number of reflux episodes, frequency of
      epigastric fullness, and the duration of walking around q12 hours were recorded
      in the first 48 hours post-operation. Results: Eighty patients were enrolled into
      the study. Promethazine group were found to significantly reduce the incidence of
      PONV in the first 24 hours compared with the other group (41% vs. 97.5%),
      relative risk = 0.042 [95% CI = 0.006, 0.299]. The mean numbers of epigastric
      fullness and severity of epigastria pain were lower in the promethazine group (P
      = 0.01) and the total opioid requirement was also reduced in promethazine group
      (32.1 +/- 2.6 VS .68.5 +/- 4.6 mg). However, the patients in the promethazine
      group were more sedated, which caused the duration of walking q12 hours in this
      group to decrease. Conclusions: In morbidly obese patients undergoing
      laparoscopic gastric plication, promethazine/dexametasone was more effective than
      Metoclopramide/dexametasone in preventing and reducing the incidence of nausea,
      epigastric fullness, and reflux. That combination was also more effective than
      Metoclopramide in reducing the severity of epigastric pain.

PMID- 29226111
TI  - Comparison of Electronic Learning Versus Lecture-based Learning in Improving
      Emergency Medicine Residents' Knowledge About Mild Induced Hypothermia After
      Cardiac Arrest.
AB  - Background: The process of medical education depends on several issues such as
      training materials, students, professors, educational fields, and the applied
      technologies. The current study aimed at comparing the impacts of e-learning and
      lecture-based learning of mild induced hypothermia (MIH) after cardiac arrest on
      the increase of knowledge among emergency medicine residents. Methods: In a pre-
      and post-intervention study, MIH after cardiac arrest was taught to 44 emergency
      medicine residents. Residents were randomly divided into 2 groups. The first
      group included 21 participants (lecture-based learning) and the second had 23
      participants (e-learning). A 19-item questionnaire with approved validity and
      reliability was employed as the pretest and posttest. Then, data were analyzed
      with SPSS software version 17.0. Results: There was no statistically significant
      difference in terms of the learning method between the test scores of the 2
      groups (P = 0.977). Conclusions: E-learning and lecture-based learning methods
      was effective in augmentation of residents of emergency medicine knowledge about
      MIH after cardiac arrest; nevertheless, there was no significant difference
      between these mentioned methods.

PMID- 29226113
TI  - In Vitro Evaluation of Vegf-Pseudomonas Exotoxin: A Conjugated on Tumor Cells.
AB  - Background: Angiogenesis which occurs mandatory in solid tumors, is a critical
      step in malignancy progression. Vascular endothelial growth factor (VEGF) is
      mainly responsible for angiogenesis process and facilitates the formation of new
      vessels. Distribution of monoclonal antibodies against VEGF or VEGF receptor
      (VEGFR) into the solid tumors is limited because of their huge dimensions.
      Moreover, many investigations have demonstrated the usefulness of immunotoxins to
      halt angiogenesis in solid tumors. Materials and Methods: We designed, expressed
      and evaluated the cytotoxicity of a novel nano-immunotoxin composed of VEGF
      splice variant containing 121 amino acids (VEGF121) and truncated the exotoxin A
      of Pseudomonas aeruginosa (PE38-KDEL). The fusion protein VEGF121-PE38 was
      successfully cloned and expressed in Escherichia coli, purified by Ni+ 2 affinity
      chromatography. The fusion protein was subsequently subjected to refolding using
      the reduced and oxidized glutathione. Results: The expression level of the fusion
      protein reached to 1 mg/ml. The VEGF121-PE38 immunotoxin showed a 59 KDa MW which
      had cytotoxic effect on HUVEC and 293/KDR cells as low and high expressing VEGFR2
      cells, respectively. But the cytotoxicity on 293/KDR was 100 folds more than that
      of VEGFR2 low expressing cell HUVEC. Conclusion: The designed immunotoxin showed
      more selectivity for higher VEGFR2 expressing cells in vitro.

PMID- 29226114
TI  - Comparison the Effects of Intraoperative Labetalol and Lidocaine on Postoperative
      Blood Pressure and Heart Rate in Brain Surgeries.
AB  - Background: Long-term anesthesia applied in some operations, especially in
      neurosurgical operations leads to unwanted complications. This study aimed to
      compare the effect of intraoperative labetalol and lidocaine injection on the
      rate of changes in postoperative blood pressure and heart beat in patients
      undergoing brain operation. Materials and Methods: This is a simple double-blind
      randomized clinical trial study conducted in Al-Zahra and Kashani Hospitals on 90
      patients' candidate for craniotomy operation with the age range of 18-65 years,
      Glasgow Coma Scale (GCS) >=13 before anesthesia, physical class of American
      Society of Anesthesiologists I, II, insensitivity to labetalol who were divided
      into two groups of 45 individuals in the random allocation method. To start
      anesthesia, fentanil 1.5 mg per 1 kg of body weight, midazolam 5 mg, propofol 2
      mg/kg and then, atracurium 0.15 mg/kg and lidocaine 1.5 mg/kg were used. The rate
      of patients' bucking and blood pressure were checked at GCS time after operation
      and in patients' recovery in terms of 0, 5, 10, 20 and 30 min after arrival in
      the recovery room and 1 h later. Results: There was no significant difference in
      terms of hemodynamic parameters during the period of operation and recovery and
      at the time of extubation and during the study, no case of bradicardia,
      hypotension, tachycardia or hypertension was observed in the patients of both
      groups. Conclusion: Using labetalol in craniotomy surgery is helpful for two main
      reasons that are the proper control of intraoperative and postoperative blood
      pressure and prevention of postoperative reactions, especially cough and if there
      is no contraindication for using it, it is recommended.

PMID- 29226112
TI  - Formation of the Legionella Replicative Compartment at the Crossroads of
      Retrograde Trafficking.
AB  - Retrograde trafficking from the endosomal system through the Golgi apparatus back
      to the endoplasmic reticulum is an essential pathway in eukaryotic cells, serving
      to maintain organelle identity and to recycle empty cargo receptors delivered by
      the secretory pathway. Intracellular replication of several bacterial pathogens,
      including Legionella pneumophila, is restricted by the retrograde trafficking
      pathway. L. pneumophila employs the Icm/Dot type IV secretion system (T4SS) to
      form the replication-permissive Legionella-containing vacuole (LCV), which is
      decorated with multiple components of the retrograde trafficking machinery as
      well as retrograde cargo receptors. The L. pneumophila effector protein RidL is
      secreted by the T4SS and interferes with retrograde trafficking. Here, we review
      recent evidence that the LCV interacts with the retrograde trafficking pathway,
      discuss the possible sites of action and function of RidL in the retrograde
      route, and put forth the hypothesis that the LCV is an acceptor compartment of
      retrograde transport vesicles.

PMID- 29226115
TI  - Body Composition in Crohn's Disease and Ulcerative Colitis: Correlation with
      Disease Severity and Duration.
AB  - Background: Results on body composition in Crohn's disease (CD) and ulcerative
      colitis (UC) have been heterogeneous and are lacking from Asia. Present study
      assessed body composition in CD/UC and correlated it with disease
      severity/duration. Methods: Patients of CD/UC following between Dec 2014 and Dec
      2015 who consented for bioimpedance analysis for body fat measurement were
      included. Lean mass and fat-free mass index (FFMI) were calculated with standard
      formulae. Visceral fat area (VFA), subcutaneous fat area (SCA), and visceral to
      subcutaneous fat ratio (VF/SC) were evaluated in CD patients on abdominal CT.
      Results: Lean mass in CD (n = 44, mean age: 41.2 +/- 15.8 years, 73% males) was
      significantly lower than UC (n = 53, mean age: 33.2 +/- 11.2 years, 68% males;
      44.2 +/- 7.8 versus 48.3 +/- 8.4 Kg, p = 0.01). In both UC/CD, disease severity
      was associated with nonsignificant decline in BMI (UC: 22.1 +/- 4.9 versus 20.2
      +/- 3.2 versus 19.9 +/- 3.2 kg/m2, p = 0.23; CD: 22.1 +/- 4.2 versus 19.9 +/- 2.3
      versus 19.7 +/- 4.2 kg/m2, p = 0.18) and fat mass (UC: 10.9 +/- 8.9 versus 8.1 +/
      5.9 versus 5.7 +/- 3.6 kg, p = 0.14; CD: 11.2 +/- 7 versus 7.9 +/- 4.4 versus
      7.2 +/- 5.9 kg, p = 0.16), and disease duration was associated with significant
      decline in FFMI (p < 0.05). In CD, disease severity was associated with
      nonsignificant decline in SCA and increase in VF/SC. Conclusions: CD patients
      have lower lean mass than UC. Body fat decreases with increasing disease severity
      and fat-free mass decreases with increasing disease duration in both UC/CD.

PMID- 29226116
TI  - Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease.
AB  - Aim: To examine the association between lifetime alcohol consumption and
      significant liver disease in type 2 diabetic patients with NAFLD. Methods: A
      cross-sectional study assessing 151 patients with NAFLD at risk of clinically
      significant liver disease. NAFLD fibrosis severity was classified by transient
      elastography; liver stiffness measurements >=8.2 kPa defined significant
      fibrosis. Lifetime drinking history classified patients into nondrinkers, light
      drinkers (always <=20 g/day), and moderate drinkers (any period with intake >20
      g/day). Result: Compared with lifetime nondrinkers, light and moderate drinkers
      were more likely to be male (p = 0.008) and to be Caucasian (p = 0.007) and to
      have a history of cigarette smoking (p = 0.000), obstructive sleep apnea (p =
      0.003), and self-reported depression (p = 0.003). Moderate drinkers required >=3
      hypoglycemic agents to maintain diabetic control (p = 0.041) and fibrate
      medication to lower blood triglyceride levels (p = 0.044). Compared to lifetime
      nondrinkers, light drinkers had 1.79 (95% CI: 0.67-4.82; p = 0.247) and moderate
      drinkers had 0.91 (95% CI: 0.27-3.10; p = 0.881) times the odds of having liver
      stiffness measurements >=8.2 kPa (adjusted for age, gender, and body mass index).
      Conclusions: In diabetic patients with NAFLD, light or moderate lifetime alcohol
      consumption was not significantly associated with liver fibrosis. The impact of
      lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in
      particular obstructive sleep apnea and hypertriglyceridemia, requires further
      investigation.

PMID- 29226118
TI  - Identification of a Novel Heterozygous De Novo 7-bp Frameshift Deletion in PBX1
      by Whole-Exome Sequencing Causing a Multi-Organ Syndrome Including Bilateral
      Dysplastic Kidneys and Hypoplastic Clavicles.
AB  - Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT)
      represent the primary cause of chronic kidney disease in children. Many genes
      have been attributed to the genesis of this disorder. Recently,
      haploinsufficiency of PBX1 caused by microdeletions has been shown to result in
      bilateral renal hypoplasia and other organ malformations. Materials and methods:
      Here, we report on a 14-year-old male patient with congenital bilateral
      dysplastic kidneys, cryptorchidism, hypoplastic clavicles, developmental delay,
      impaired intelligence, and minor dysmorphic features. Presuming a syndromic
      origin, we performed SNP array analysis to scan for large copy number variations
      (CNVs) followed by whole-exome sequencing (WES). Sanger sequencing was done to
      confirm the variant's de novo status. Results: SNP array analysis did not reveal
      any microdeletions or -duplications larger than 50 or 100 kb, respectively. WES
      identified a novel heterozygous 7-bp frameshift deletion in PBX1 (c.413_419del,
      p.Gly138Valfs*40) resulting in a loss-of-function. The de novo status could be
      confirmed by Sanger sequencing. Discussion: By WES, we identified a novel
      heterozygous de novo 7-bp frameshift deletion in PBX1. Our findings expand the
      spectrum of causative variants in PBX1-related CAKUT. In this case, WES proved to
      be the apt technique to detect the variant responsible for the patient's
      phenotype, as single gene testing is not feasible given the multitude of genes
      involved in CAKUT and SNP array analysis misses rare single-nucleotide variants
      and small Indels.

PMID- 29226117
TI  - Pediatric Anti-N-Methyl-d-Aspartate Receptor Encephalitis: A Review with Pooled
      Analysis and Critical Care Emphasis.
AB  - Purpose: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being
      recognized with increasing frequency among children. Given the paucity of
      evidence to guide the critical care management of these complex patients, we
      provide a comprehensive review of the literature with pooled analysis of
      published case reports and case series. Methods: We performed a comprehensive
      literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant
      published studies. The literature search was conducted using the terms NMDA, anti
      NMDA, Anti-N-methyl-d-aspartate, pediatric encephalitis, and anti-NMDAR and
      included articles published between 2005 and May 1, 2016. Results: Forty-eight
      references met inclusion criteria accounting for 373 cases. For first-line
      treatments, 335 (89.8%) received high-dose corticosteroids, 296 received
      intravenous immunoglobulin (79.3%), and 116 (31%) received therapeutic plasma
      exchange. In these, 187 children (50.1%) had a full recovery with only minor
      deficits, 174 patients (46.7%) had partial recovery with major deficits, and 12
      children died. In addition, 14 patients were reported to require mechanical
      ventilation. Conclusion: Anti-NMDA encephalitis is a formidable disease with
      great variation in clinical presentation and response to treatment. With early
      recognition of this second most common cause of pediatric encephalitis, a
      multidisciplinary approach by physicians may provide earlier access to first- and
      second-line therapies. Future studies are needed to examine the efficacy of these
      current therapeutic strategies on long-term morbidity.

PMID- 29226119
TI  - Substitution of Formal and Informal Home Care Service Use and Nursing Home
      Service Use: Health Outcomes, Decision-Making Preferences, and Implications for a
      Public Health Policy.
AB  - Objectives: The purposes of this study are: (1) to empirically identify decision
      making preferences of long-term health-care use, especially informal and formal
      home care (FHC) service use; (2) to evaluate outcomes vs. costs based on
      substitutability of informal and FHC service use; and (3) to investigate health
      outcome disparity based on substitutability. Methodology and data: The methods of
      ordinary least squares, a logit model, and a bivariate probit model are used by
      controlling for socioeconomic, demographic, and physical/mental health factors to
      investigate outcomes and costs based substitutability of informal and formal
      health-care use. The data come from the 2013 Japanese Study of Aging and
      Retirement (JSTAR), which is designed by Keizai-Sangyo Kenkyu-jo, Hitotsubashi
      University, and the University of Tokyo. The JSTAR is a globally comparable data
      survey of the elderly. Results: There exists a complement relationship between
      the informal home care (IHC) and community-based FHC services, and the
      elasticity's ranges from 0.18 to 0.22. These are reasonable results, which show
      that unobservable factors are positively related to IHC and community-based FHC,
      but negatively related to nursing home (NH) services based on our bivariate
      probit model. Regarding health-care outcome efficiency issue, the IHC is the best
      one among three types of elderly care: IHC, community-based FHC, and NH services.
      Health improvement/outcome of elderly with the IHC is heavier concentrated on IHC
      services than the elderly care services by community-based FHC and NH care
      services. Conclusion: Policy makers need to address a diversity of health
      outcomes and efficiency of services based on providing services to elderly
      through resource allocation to the different types of long-term care. A provision
      of partial or full compensation for elderly care at home is recommendable and a
      viable option to improve their quality of lives.

PMID- 29226120
TI  - Teaching Undergraduate Students to Visualize and Communicate Public Health Data
      with Infographics.
AB  - The purpose of this study was to explore the degree to which an infographic
      assignment facilitated student learning around health science issues, as well as
      the ways in which the assignment was an effective teaching tool. The objectives
      of the assignment were to (1) understand the purposes of and potential uses for
      infographics, (2) cultivate creative visual communication skills, and (3)
      disseminate a complex health topic to diverse audiences. The infographic
      assignment was developed at Montana State University and piloted at Portland
      State University. Students were assigned to small groups of three or four to
      create an infographic focused on a health science issue. The assignment was
      divided into four steps: brainstorming, developing, designing, and finalizing.
      Focus groups were conducted to assess how learning occurred throughout the
      assignment and identify any opportunities for modification of the assignment.
      This study was conducted with freshman students enrolled at Portland State
      University, a public university located in downtown Portland, OR, USA. Thirty
      four students completed the assignment and 31 students participated in one of
      three focus groups. Four themes emerged from focus groups: (1) Communicating
      Science-Related Topics to Non-experts, (2) Developing Professional Skills, (3)
      Understanding Health Issues, and (4) Overall Experience. This article outlines
      the assignment, discusses focus group results, and presents assignment
      modifications. It is clear that the infographic assignment facilitated learning
      about accessing and translating data. This assignment is ideally suited for use
      with diverse college-age audiences in health education and health promotion
      fields.

PMID- 29226121
TI  - Facts and Fallacies in the Debate on Glyphosate Toxicity.
AB  - The safety profile of the herbicide glyphosate and its commercial formulations is
      controversial. Reviews have been published by individuals who are consultants and
      employees of companies commercializing glyphosate-based herbicides in support of
      glyphosate's reapproval by regulatory agencies. These authors conclude that
      glyphosate is safe at levels below regulatory permissible limits. In contrast,
      reviews conducted by academic scientists independent of industry report toxic
      effects below regulatory limits, as well as shortcomings of the current
      regulatory evaluation of risks associated with glyphosate exposures. Two authors
      in particular (Samsel and Seneff) have published a series of commentaries
      proposing that long-term exposure to glyphosate is responsible for many chronic
      diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections,
      osteoporosis, infertility, and birth defects). The aim of this review is to
      examine the evidential basis for these claimed negative health effects and the
      mechanisms that are alleged to be at their basis. We found that these authors
      inappropriately employ a deductive reasoning approach based on syllogism. We
      found that their conclusions are not supported by the available scientific
      evidence. Thus, the mechanisms and vast range of conditions proposed to result
      from glyphosate toxicity presented by Samsel and Seneff in their commentaries are
      at best unsubstantiated theories, speculations, or simply incorrect. This
      misrepresentation of glyphosate's toxicity misleads the public, the scientific
      community, and regulators. Although evidence exists that glyphosate-based
      herbicides are toxic below regulatory set safety limits, the arguments of Samsel
      and Seneff largely serve to distract rather than to give a rational direction to
      much needed future research investigating the toxicity of these pesticides,
      especially at levels of ingestion that are typical for human populations.

PMID- 29226122
TI  - Does Mineralocorticoid Receptor Antagonism Prevent Calcineurin Inhibitor-Induced
      Nephrotoxicity?
AB  - Calcineurin inhibitors have markedly reduced acute rejection rates in renal
      transplantation, thus significantly improved short-term outcome. The beneficial
      effects are, however, tampered by acute and chronic nephrotoxicity leading to
      interstitial fibrosis and tubular atrophy, which impairs long-term allograft
      survival. The mineralocorticoid hormone aldosterone induces fibrosis in numerous
      organs, including the kidney. Evidence from animal models suggests a beneficial
      effect of aldosterone antagonism in reducing calcineurin inhibitor-induced
      nephrotoxicity. This review summarizes current evidence of mineralocorticoid
      receptor antagonism in animal models of calcineurin inhibitor-induced
      nephrotoxicity and the results from studies of mineralocorticoid antagonism in
      renal transplant patients.

PMID- 29226123
TI  - Open Repair of a 12-cm Posttraumatic Aneurysm of Right Subclavian Artery.
AB  - Purpose: To present a rare case of a patient with a 12-cm posttraumatic right
      subclavian artery aneurysm successfully treated with aneurysmectomy and
      innominate-axillary bypass. Case report: A 54-year-old man presented to the
      emergency department due to progressive dyspnea and hoarseness of voice. His
      medical record was unremarkable except that he had right-sided pneumothorax and
      multiple rib fractures from a car accident 16 years ago. A chest X-ray showed a
      mass in the upper lobe of the right lung, and the patient was hospitalized for
      further investigation. A computed tomography (CT) with intravenous contrast of
      the thorax was performed, which depicted a giant aneurysm of the right subclavian
      artery. Vascular and cardiothoracic surgeons were consulted immediately, and the
      operation was scheduled. Aneurysmectomy and innominate-axillary bypass were
      performed. The patient had an uncomplicated progress and was discharged on 5 days
      followed by a single antiplatelet therapy and symptom-free. Conclusion:
      Posttraumatic subclavian artery aneurysm is a rare entity. Imaging of the thorax
      is essential for the diagnosis and surgical preparation of the patient. Open
      repair remains the gold standard therapy for subclavian artery aneurysm despite
      the improvements in endovascular surgery in such huge aneurysms.

PMID- 29226125
TI  - Stattic Enhances Radiosensitivity and Reduces Radio-Induced Migration and
      Invasion in HCC Cell Lines through an Apoptosis Pathway.
AB  - Purpose: Signal transducer and activator of transcription factor 3 (STAT3) is
      involved in tumorigenesis, development, and radioresistance of many solid tumors.
      The aim of this study is to investigate the effects of stattic (an inhibitor of
      STAT3) on the radiosensitivity and radio-induced migration and invasion ability
      in hepatocellular carcinoma (HCC) cell lines. Methods: HCC cells were treated
      with stattic, and cell survival rate was analyzed through CCK-8 assay.
      Radiosensitivity was evaluated using cloning formation analysis; STAT3, p-STAT3,
      and apoptosis related proteins were detected by western blot. Radio-induced
      migration and invasion ability in HCC cells were analyzed by wound-healing assay
      and transwell test. Results: Stattic inhibits the expression of p-STAT3 and
      reduces cell survival in a dose-dependent manner in HCC cell lines, and the IC50
      values for Hep G2, Bel-7402, and SMMC-7721 are 2.94 MUM, 2.5 MUM, and 5.1 MUM,
      respectively. Cloning formation analysis shows that stattic enhances the
      radiosensitivity of HCC cells. Wound-healing assay and transwell test show that
      stattic inhibits radio-induced migration and invasion. Further study indicates
      that stattic promotes radio-induce apoptosis through regulating the expression of
      apoptosis related proteins in HCC cells. Conclusion: Stattic enhances
      radiosensitivity and reduces radio-induced migration and invasion ability in HCC
      cells probably through apoptosis pathway.

PMID- 29226126
TI  - Prevalence of Autonomic Dysreflexia in Patients with Spinal Cord Injury above T6.
AB  - Objective: To investigate the prevalence of autonomic dysreflexia (AD) using
      ambulatory blood pressure monitoring (ABPM) and the autonomic dysfunction
      following spinal cord injury (ADFSCI) questionnaire in patients with spinal cord
      injury (SCI) above T6. Methods: Twenty-eight patients diagnosed with SCI above T6
      were enrolled. ABPM and ADFSCI were utilized to assess AD. Using ABPM, systolic
      blood pressure (SBP), diastolic blood pressure, and heart rate (HR) were measured
      at 30-minute intervals. AD was defined as SBP 20 mmHg higher than basal SBP, and
      the number of AD events was counted. The ADFSCI questionnaire evaluates the
      severity and frequency of the AD symptoms. Results: According to the ABPM, AD
      occurred in 26 patients and AD events occurred 5.8 +/- 4.7 times. Average daytime
      and nighttime SBP were 119.9 +/- 18.8 mmHg and 123.8 +/- 21.2 mmHg, respectively,
      and the nighttime mean SBP appeared to be 4 mmHg higher than daytime mean SBP.
      These findings suggest the loss of nocturnal BP dipping in SCI patients. ADFSCI
      results revealed that 16 of the patients evaluated were symptomatic while 12 were
      asymptomatic. Conclusion: AD following SCI above T6 was highly prevalent and
      several patients seemed asymptomatic. These results suggest the necessity of
      proper diagnostic and therapeutic interventions for managing AD.

PMID- 29226127
TI  - The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot
      and-Mouth Disease Virus Replication.
AB  - Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which
      affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays
      an important role in FMDV pathogenesis. However, the interacting partners of VP1
      in host cells and the effects of these interactions in FMDV replication remain
      incompletely elucidated. Here, we identified a porcine cell protein,
      serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast
      two-hybrid system. The VP1-STK3 interaction was further confirmed by
      coimmunoprecipitation experiments in human embryonic kidney 293T and porcine
      kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180-214) of
      VP1 was essential for its interaction with STK3. The effects of overexpression
      and underexpressing of STK3 in PK-15 cells were assessed, and the results
      indicated that STK3 significantly inhibited FMDV replication. Our data expand the
      role of STK3 during viral infection, provide new information regarding the host
      cell kinases that are involved in viral replication, and identify potential
      targets for future antiviral strategies.

PMID- 29226128
TI  - Amplitude, Latency, and Peak Velocity in Accommodation and Disaccommodation
      Dynamics.
AB  - The aim of this work was to ascertain whether there are differences in amplitude,
      latency, and peak velocity of accommodation and disaccommodation responses when
      different analysis strategies are used to compute them, such as fitting different
      functions to the responses or for smoothing them prior to computing the
      parameters. Accommodation and disaccommodation responses from four subjects to
      pulse changes in demand were recorded by means of aberrometry. Three different
      strategies were followed to analyze such responses: fitting an exponential
      function to the experimental data; fitting a Boltzmann sigmoid function to the
      data; and smoothing the data. Amplitude, latency, and peak velocity of the
      responses were extracted. Significant differences were found between the peak
      velocity in accommodation computed by fitting an exponential function and
      smoothing the experimental data (mean difference 2.36 D/s). Regarding
      disaccommodation, significant differences were found between latency and peak
      velocity, calculated with the two same strategies (mean difference of 0.15 s and 
      3.56 D/s, resp.). The strategy used to analyze accommodation and disaccommodation
      responses seems to affect the parameters that describe accommodation and
      disaccommodation dynamics. These results highlight the importance of choosing the
      most adequate analysis strategy in each individual to obtain the parameters that
      characterize accommodation and disaccommodation dynamics.

PMID- 29226129
TI  - The Relationship between Dental Follicle Width and Maxillary Impacted Canines'
      Descriptive and Resorptive Features Using Cone-Beam Computed Tomography.
AB  - Objectives: To assess the relationship between dental follicle width and
      maxillary impacted canines' descriptive and resorptive features with three
      dimensional (3D) cone-beam computed tomography (CBCT). Methods: The study
      comprised 102 patients with cone-beam computed tomography 3D images and a total
      of 140 impacted canines. The association between maxillary impacted canine dental
      follicle width and the variables of gender, impaction side (right and left),
      localization of impacted canine (buccal, central, and palatal), and resorption of
      the adjacent laterals was compared. Measurements were analyzed with Student's t
      test, Kruskal-Wallis test, and Mann-Whitney U statistical test. Results:
      According to gender, no statistically significant differences were found in the
      follicle size of the maxillary impacted canine between males and females (p >
      0.05). Widths of the follicles were determined for the right and left impaction
      sides, and no statistically significant relation was found (p > 0.05). There were
      statistically significant differences between root resorption degrees of lateral
      incisors and maxillary impacted canine follicle width (p < 0.05). Statistically
      significant higher follicle width values were present in degree 2 (mild)
      resorption than in degree 1 (no) and degree 3 (moderate) resorption samples (p <
      0.05). Conclusions: No significant correlation was found between follicle width
      and the variables of gender, impaction side, and localization of maxillary
      impacted canines. Our study could not confirm that increased dental follicle
      width of the maxillary impacted canines exhibited more resorption risk for the
      adjacent lateral incisors.

PMID- 29226130
TI  - In Vitro Activity of Lactobacilli with Probiotic Potential Isolated from Cocoa
      Fermentation against Gardnerella vaginalis.
AB  - Study of the probiotic potential of microorganisms isolated from fermented foods
      has been increasing, especially studies related to lactobacilli. In intestinal
      models, lactobacilli have demonstrated beneficial properties, such as anti
      inflammatory activity and increased antibody production, but the molecular
      mechanisms involving probiotic and antagonistic action as well as their effect on
      human vaginal cells have not yet been fully elucidated. The aim of this study was
      to evaluate the functional and antagonistic properties of three strains of
      lactobacilli isolated from cocoa fermentation (Lactobacillus fermentum 5.2, L.
      plantarum 6.2, and L. plantarum 7.1) against Gardnerella vaginalis. Our results
      show that the lactobacilli have potential use as probiotics, since they have high
      hydrophobicity and autoaggregation properties and effectively adhere to vaginal
      cells. Metabolites secreted into the culture medium and whole cells of the
      strains under study are capable of interfering with the growth of G. vaginalis to
      different degrees. The elucidation of the antagonistic mechanisms as well as
      their effect on human cells may be useful in the development of a product
      containing such microorganisms or products secreted by them.

PMID- 29226124
TI  - Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions.
AB  - The science behind psychotherapy has garnered considerable interest, as objective
      measures are being developed to map the patient's subjective change over the
      course of treatment. Prenatal and early life influences have a lasting impact on
      how genes are expressed and the manner in which neural circuits are consolidated.
      Transgenerationally transmitted epigenetic markers as well as templates of
      enhanced thought flexibility versus evasion can be passed down from parent to
      child. This influences gene expression/repression (impacting neuroplasticity) and
      kindling of neurocircuitry which can perpetuate maladaptive cognitive processing
      seen in a number of psychiatric conditions. Importantly, genetic factors and the
      compounding effects of early life adversity do not inexorably lead to certain
      fated outcomes. The concepts of vulnerability and resilience are becoming more
      integrated into the framework of "differential susceptibility," speaking to how
      corrective environmental factors may promote epigenetic change and reconfigure
      neural templates, allowing for symptomatic improvement. Psychotherapy is one such
      factor, and this review will focus on our current knowledge of its epigenetic and
      neurocircuitry impact.

PMID- 29226131
TI  - Risk Factors of Delirium in Sequential Sedation Patients in Intensive Care Units.
AB  - Background: Delirium is a primary adverse event in ventilated patients who
      receive long-term monosedative treatment. Sequential sedation may reduce these
      adverse effects. This study evaluated risk factors for delirium in sequential
      sedation patients. Methods: A total of 141 patients who underwent sequential
      sedation were enrolled. Delirium was diagnosed using Confusion Assessment Method
      for the Intensive Care Unit (CAM-ICU) scale. Univariate and multivariate Cox
      proportional hazards regressions were used to predict risk factors. Results:
      Older age (>=51) (RR = 2.432, 95% CL 1.316-4.494, p = 0.005), higher SOFA score
      (>=14) (RR = 2.022, 95% CL 1.076-3.798, p = 0.029), regular smoking (RR = 2.366,
      95% CL 1.277-4.382, p = 0.006), and higher maintenance dose of midazolam (RR =
      1.052, 95% CL 1.000-1.107, p = 0.049) and fentanyl (RR = 1.045, 95% CL 1.019
      1.072, p = 0.001) when patients met sequential criteria, were independent risk
      factors of delirium. Sequential sedation with dexmedetomidine (RR = 0.448, 95% CL
      0.209-0.963, p = 0.040) was associated with a lower risk of delirium.
      Conclusions: Older age, higher SOFA score, regular smoking, and higher
      maintenance dose of midazolam and fentanyl when patients met sequential criteria
      were independent risk factors of delirium in sequential sedation patients.
      Sequential sedation with dexmedetomidine reduced risk of delirium.

PMID- 29226132
TI  - Effective Range of Percutaneous Posterior Full-Endoscopic Paramedian Cervical
      Disc Herniation Discectomy and Indications for Patient Selection.
AB  - The objective was to investigate the effective and safe range of paramedian CDH
      by percutaneous posterior full-endoscopy cervical intervertebral disc nucleus
      pulposus resection (PPFECD) to provide a reference for indications and patient
      selection. Sixteen patients with CDH satisfied the inclusion criteria. Before
      surgery the patients underwent cervical spine MRI, and the distance between the
      dural sac and herniated disc was measured. An assessment was performed by MRI
      immediately after surgery, measuring the distance between dural sac and medial
      border of discectomy (DSMD). The preoperative average distance between the dural
      sac and peak of the herniated disc (DSPHD) was 3.87 +/- 1.32 mm; preoperative
      average distance between dural sac and medial border of herniated disc (DSMHD)
      was 6.91 +/- 1.21 mm and an average distance of postoperative DSMD was 5.41 +/-
      1.40 mm. Postoperative VAS of neck and shoulder pain was significantly decreased
      but JOA was significantly increased in each time point compared with preoperative
      ones. In summary, the effective range of PPFECD to treat paramedian CDH was 5.41
      +/- 1.40 mm, indicating that DSMHD and DSPHD were within 6.91 +/- 1.21 mm and
      3.87 +/- 1.32 mm, respectively. PPFECD surgery is, therefore, a safe and
      effective treatment option for patients with partial paramedian cervical disc
      herniation.

PMID- 29226133
TI  - Circulating Interferon-lambda3, Responsiveness to HBV Vaccination, and HBV/HCV
      Infections in Haemodialysis Patients.
AB  - The IFN-lambda3 gene (IFNL3) plays a role in HCV clearance. We investigated
      circulating IFN-lambda3 and IFNL3 SNPs in haemodialysis patients who differed in
      their response to HBV vaccination and their HBV/HCV infection status. In 201
      patients, plasma IFN-lambda3 was determined using ELISA. IFNL3 SNPs (rs12979860,
      rs8099917) were genotyped using HRM analysis. Differences in IFN-lambda3 levels
      were shown between responders and nonresponders to HBV vaccination and between
      HBsAg-positive patients and those who developed anti-HBs after infection and
      became HBsAg negative. HBV vaccine responders without HCV resolution revealed
      lower IFN-lambda3 than noninfected responders. HBsAg/HCV RNA-positive subjects
      showed lower IFN-lambda3 than patients positive only for HCV RNA or subjects who
      resolved both infections. Circulating IFN-lambda3 correlated positively with anti
      HBs and negatively with positive HCV RNA testing in the adjusted regression
      analyses. HBV vaccine nonresponders, HBsAg-positive patients, and subjects with
      replicating HCV composed a group with unfavourable outcomes. Responders to HBV
      vaccination, subjects who became HBsAg negative, and those who cleared HCV were
      analysed as having favourable outcomes. The latter showed higher IFN-lambda3 but
      did not differ in distribution of IFNL3 SNPs compared with subjects with
      unfavourable outcomes. Higher IFN-lambda3 concentrations are associated with
      response to HBV vaccination, self-limited HBV infection, and HCV resolution.

PMID- 29226134
TI  - Success Rates of Pulpotomies in Primary Molars Using Calcium Silicate-Based
      Materials: A Randomized Control Trial.
AB  - Objective: The aim of this study was to evaluate and compare, both clinically and
      radiographically, the effects of calcium silicate-based materials (i.e., ProRoot
      MTA [PR-MTA], MTA-Plus [MTA-P], and Biodentine [BD]) and ferric sulfate [FS] in
      pulpotomy of primary molars. Materials and Methods: In this randomized clinical
      trial, 29 healthy 5- to 7-year-old children with at least four carious primary
      molars with no clinical or radiographic evidence of pulp degeneration were
      enrolled. The pulpotomy agents were assigned as follows: Group 1: BD; Group 2:
      MTA-P; Group 3: PR-MTA; and Group 4: FS. Clinical and radiographic evaluations
      were performed at 6, 12, and 24 months. Data were analyzed using chi-square
      tests. Results: Total success rates at 24 months were 82.75%, 86.2%, 93.1%, and
      75.86%, respectively. No statistically significant differences in total success
      rates were observed among the groups at 6-, 12-, and 24-month follow-ups. When
      the groups were compared according to follow-up times, the success rates in each
      group did not vary significantly among the 6-12-month, 6-24-month, or 12-24-month
      periods (p > 0.05). Conclusion: Although the success rates of BD, MTA-P, MTA-PR,
      and FS did not differ significantly, calcium silicate-based materials appeared to
      be more appropriate than FS in clinical practice.

PMID- 29226135
TI  - A Novel Cyclophilin B Gene in the Red Tide Dinoflagellate Cochlodinium
      polykrikoides: Molecular Characterizations and Transcriptional Responses to
      Environmental Stresses.
AB  - The marine dinoflagellate Cochlodinium polykrikoides is one of the most common
      ichthyotoxic species that causes harmful algal blooms (HABs), which leads to
      ecological damage and huge economic loss in aquaculture industries. Cyclophilins
      (CYPs) belong to the immunophilin superfamily, and they may play a role in the
      survival mechanisms of the dinoflagellate in stress environments. In the present
      study, we identified a novel cyclophilin gene from C. polykrikoides and examined
      physiological and gene transcriptional responses to biocides copper sulphate
      (CuSO4) and sodium hypochlorite (NaOCl). The full length of CpCYP was 903 bp,
      ranging from the dinoflagellate splice leader (DinoSL) sequence to the polyA
      tail, comprising a 639 bp ORF, a 117 bp 5'-UTR, and a 147 bp 3'-UTR. Motif and
      phylogenetic comparisons showed that CpCYP was affiliated to group B of CYP. In
      biocide stressors, cell counts, chlorophyll a, and photosynthetic efficiency
      (Fv/Fm) of C. polykrikoides were considerably decreased in both exposure time-
      and dose-dependent manners. In addition, CpCYP gene expression was significantly
      induced after 24 h exposure to the biocide-treated stress conditions. These
      results indicate an effect of the biocides on the cell physiology and expression
      profile of CpCYP, suggesting that the gene may play a role in environmental
      stress responses.

PMID- 29226137
TI  - Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis
      Using Bioinformatics Analysis.
AB  - Background: Coronary artery atherosclerosis is a chronic inflammatory disease.
      This study aimed to identify the key changes of gene expression between early and
      advanced carotid atherosclerotic plaque in human. Methods: Gene expression
      dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO), including 16
      advanced and 13 early stage atherosclerotic plaque samples from human carotid.
      Differentially expressed genes (DEGs) were analyzed. Results: 42,450 genes were
      obtained from the dataset. Top 100 up- and downregulated DEGs were listed.
      Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      identification were performed. The result of functional and pathway enrichment
      analysis indicted that the immune system process played a critical role in the
      progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI)
      networks were performed either. Top 10 hub genes were identified from PPI network
      and top 6 modules were inferred. These genes were mainly involved in chemokine
      signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion,
      and regulation of actin cytoskeleton. Conclusion: The present study indicated
      that analysis of DEGs would make a deeper understanding of the molecular
      mechanisms of atherosclerosis development and they might be used as molecular
      targets and diagnostic biomarkers for the treatment of atherosclerosis.

PMID- 29226136
TI  - A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake
      Venom.
AB  - This work reports the purification and functional characterization of BmooPAi, a
      platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The
      toxin was purified by a combination of three chromatographic steps (ion-exchange
      on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity
      chromatography on HiTrapTM Heparin HP). BmooPAi was found to be a single-chain
      protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing
      conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid
      sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic,
      defibrinating, or coagulant activities and induced no significant oedema or
      hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin
      induced platelet aggregation in human platelet-rich plasma, whereas it had little
      or no effect on platelet aggregation induced by collagen and adenosine
      diphosphate. The results presented in this work suggest that BmooPAi is a toxin
      comprised of disintegrin-like and cysteine-rich domains, originating from
      autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may
      be of medical interest because it is a platelet aggregation inhibitor, which
      could potentially be developed as a novel therapeutic agent to prevent and/or
      treat patients with thrombotic disorders.

PMID- 29226139
TI  - Stochastic Dosimetry for the Assessment of Children Exposure to Uniform 50 Hz
      Magnetic Field with Uncertain Orientation.
AB  - This study focused on the evaluation of the exposure of children aging from five
      to fourteen years to 50 Hz homogenous magnetic field uncertain orientation using
      stochastic dosimetry. Surrogate models allowed assessing how the variation of the
      orientation of the magnetic field influenced the induced electric field in each
      tissue of the central nervous system (CNS) and in the peripheral nervous system
      (PNS) of children. Results showed that the electric field induced in CNS and PNS
      tissues of children were within the ICNIRP basic restrictions for general public
      and that no significant difference was found in the level of exposure of children
      of different ages when considering 10000 possible orientations of the magnetic
      field. A "mean stochastic model," useful to estimate the level of exposure in
      each tissue of a representative child in the range of age from five to fourteen
      years, was developed. In conclusion, this study was useful to deepen knowledge
      about the ELF-MF exposure, including the evaluation of variable and uncertain
      conditions, thus representing a step towards a more realistic characterization of
      the exposure to EMF.

PMID- 29226138
TI  - Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in
      Mice.
AB  - High plasma level of HDL-cholesterol (HDL-C) has been consistently associated
      with a decreased risk of atherosclerosis (AS); thus, HDL-C is considered to be an
      antiatherogenic lipoprotein. The development of novel therapies to enhance the
      atheroprotective properties of HDL may have the possibility of further reducing
      the residual AS risk. Reverse cholesterol transport (RCT) is believed to be a
      primary atheroprotective activity of HDL, which has been shown to promote the
      efflux of excess cholesterol from macrophage-derived foam cells via ATP-binding
      cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and
      scavenger receptor class B type I (SR-BI) and then transport it back to the liver
      for excretion into bile and eventually into the feces. In the current study, we
      investigated the effects of astaxanthin on RCT and AS progression in mice. The
      results showed that short- and long-term supplementation of astaxanthin promote
      RCT in C57BL/6J and ApoE-/- mice, respectively. Moreover, astaxanthin can relieve
      the plaque area of the aortic sinus and aortic cholesterol in mice. These
      findings suggest that astaxanthin is beneficial for boosting RCT and preventing
      the development of AS.

PMID- 29226140
TI  - Prevalence of Helicobacter pylori vacA Genotypes and cagA Gene in Dental Plaque
      of Asymptomatic Mexican Children.
AB  - The variability in Helicobacter pylori vacA and cagA genes has been related to
      the progression of the gastrointestinal disease; also the presence of H. pylori
      in the oral cavity has been associated with periodontal disease in adults, but,
      in children without dyspeptic symptoms, little is known about this. We evaluated
      the prevalence of H. pylori and the presence of vacA/cagA genotypes in the oral
      cavity of Mexican children without dyspeptic symptoms. The gingival status was
      measured, and dental plaque samples (n = 100) were taken. 38% of children were
      positive for H. pylori 16S rRNA gene by qPCR. A significant association between
      H. pylori oral infection and gingival status was observed (P < 0.001). In 34.6%
      (9/26) of mild gingivitis cases, s1m2 genotype was found, while s1m1 was typed in
      50% (3/6) of moderate gingivitis. The cagA prevalence among H. pylori-positive
      children was 80.8% (21/26), 83.3% (5/6), and 16.7% (1/6) of cases of mild
      gingivitis, moderate gingivitis, and nongingivitis, respectively (P < 0.001). The
      s1m1/cagA+ combinational genotype was the most detected in children with
      gingivitis. Our results suggest that the prevalence of H. pylori and detection of
      vacA/cagA genotypes-associated gastrointestinal disease in the oral cavity could
      be related to the progression of gingivitis in asymptomatic children.

PMID- 29226141
TI  - Evaluation of Immunosuppressive Therapy Use for Tracheal Transplantation with
      Trachea-Mimetic Bellows Scaffolds in a Rabbit Model.
AB  - The objective of this study was to evaluate the use of immunosuppressive therapy
      with high-dose cyclosporine, high-dose azathioprine, and a combination of low
      dose cyclosporine and azathioprine after tracheal reconstruction by using a
      trachea-mimetic graft of polycaprolactone (PCL) bellows-type scaffold in a rabbit
      model. Twenty-four healthy New Zealand white rabbits were used in the study. All
      underwent circumferential tracheal replacement using tissue-engineered tracheal
      graft, prepared from PCL bellows scaffold reinforced with silicone ring, collagen
      hydrogel, and human turbinate mesenchymal stromal cell (hTMSC) sheets. The
      control group (Group 1) received no medication. The three experimental groups
      were given daily cyclosporine intramuscular doses of 10 mg/kg (Group 2),
      azathioprine oral doses of 5 mg/kg (Group 3), and azathioprine oral doses of 2.5
      mg/kg plus cyclosporine intramuscular doses of 5 mg/kg (Group 4) for 4 weeks or
      until death. Group 1 had longer survival times compared to Group 2 or Group 3.
      Each group except for Group 1 experienced decreases in amount of nutrition and
      weight loss. In addition, compared with the other groups, Group 2 had
      significantly increased serum interleukin-2 and interferon-gamma levels 7 days
      after transplantation. The results of this study showed that the administration
      of cyclosporine and/or azathioprine after tracheal transplantation had no
      beneficial effects. Furthermore, the administration of cyclosporine had side
      effects, including extreme weight loss, respiratory distress, and diarrhea.
      Therefore, cyclosporine and azathioprine avoidance may be recommended for
      tracheal reconstruction using a native trachea-mimetic graft of PCL bellows-type
      scaffold in a rabbit model.

PMID- 29226142
TI  - Computational Exploration for Lead Compounds That Can Reverse the Nuclear
      Morphology in Progeria.
AB  - Progeria is a rare genetic disorder characterized by premature aging that
      eventually leads to death and is noticed globally. Despite alarming conditions,
      this disease lacks effective medications; however, the farnesyltransferase
      inhibitors (FTIs) are a hope in the dark. Therefore, the objective of the present
      article is to identify new compounds from the databases employing pharmacophore
      based virtual screening. Utilizing nine training set compounds along with
      lonafarnib, a common feature pharmacophore was constructed consisting of four
      features. The validated Hypo1 was subsequently allowed to screen Maybridge,
      Chembridge, and Asinex databases to retrieve the novel lead candidates, which
      were then subjected to Lipinski's rule of 5 and ADMET for drug-like assessment.
      The obtained 3,372 compounds were forwarded to docking simulations and were
      manually examined for the key interactions with the crucial residues. Two
      compounds that have demonstrated a higher dock score than the reference compounds
      and showed interactions with the crucial residues were subjected to MD
      simulations and binding free energy calculations to assess the stability of
      docked conformation and to investigate the binding interactions in detail.
      Furthermore, this study suggests that the Hits may be more effective against
      progeria and further the DFT studies were executed to understand their orbital
      energies.

PMID- 29226143
TI  - Self-Conjugation of the Enteropathogenic Escherichia coli Adherence Factor
      Plasmid of Four Typical EPEC Isolates.
AB  - The enteropathogenic Escherichia coli (EPEC) adherence factor plasmid (pEAF)
      encodes the proteins involved in the biogenesis of the bundle-forming pilus
      (BFP), a key virulence factor that mediates microcolony formation and the
      localized adherence phenotype on the surface of the host enterocytes. The
      presence or absence of this plasmid defines typical EPEC (tEPEC) and atypical
      EPEC (aEPEC), respectively. Although lateral transfer of pEAF has been evidenced
      by phylogenetic studies, conjugal transfer ability has been experimentally
      established only for two pEAF plasmids from strains isolated in the late 60s. In
      the present work, we tested the self-conjugation ability of four pEAF plasmids
      from tEPEC strains isolated between 2007 and 2008 from children in Peru and the
      potential of aEPEC to receive them. A kanamycin resistance cassette was inserted
      into donor pEAF plasmids in order to provide a selectable marker in the
      conjugation experiments. Two aEPEC isolated from the same geographic region were
      used as recipient strains along with the laboratory E. coli DH5alpha strain. Here
      we show that the four pEAF plasmids tested are self-conjugative, with transfer
      frequencies in the range of 10-6 to 10-9. Moreover, the generation of aEPEC
      strains harboring pEAF plasmids provides valuable specimens to further perform
      functional studies.

PMID- 29226144
TI  - Bioremediation: An Overview on Current Practices, Advances, and New Perspectives
      in Environmental Pollution Treatment.

PMID- 29226145
TI  - Surgical Treatment with Locoregional Flaps for the Eyelid: A Review.
AB  - Reconstruction of the eyelids after skin cancer excision can be challenging.
      Surgical treatment options are multiple; deep anatomy knowledge of lamellar
      components is mandatory to choose the most adequate surgical planning. Eyelids'
      role in vision and social relationship is critical; both function and aesthetics
      are tough to restore. Using a flap provides a satisfying texture and colour match
      with adjacent tissues and ensures short contraction during healing; furthermore,
      grafts are sometimes necessary to achieve pleasing results. Hundreds of surgical
      techniques have been described aiming for eyelid reconstruction; in our paper, we
      want to provide for our audience the most reliable and useful procedures for
      subtotal and total eyelid reconstruction following NMSC full-thickness excision.

PMID- 29226147
TI  - Antifungal Activity of Aqueous Extracts of Some Dominant Algerian Medicinal
      Plants.
AB  - Aim: This study investigated the antifungal properties of aqueous extracts
      obtained from indigenous plants that grow spontaneously in the Northern Sahara of
      Algeria. The activities of these plants in controlling two fungal species that
      belong to Fusarium genus were evaluated in an in vitro assay. Materials and
      Methods: Fresh aerial parts of four plant species (Artemisia herba alba, Cotula
      cinerea, Asphodelus tenuifolius, and Euphorbia guyoniana) were collected for the
      preparation of aqueous extracts. Two levels of dilution (10% and 20%) of the pure
      extracts were evaluated against Fusarium graminearum and Fusarium
      sporotrichioides. Results: The results of this study revealed that the A. herba
      alba, C. cinerea, A. tenuifolius, and E. guyoniana aqueous extracts are effective
      at both concentrations of 10% and 20% for the Fusarium mycelia growth inhibition.
      In particular, A. tenuifolius extract is effective against F. graminearum,
      whereas F. sporotrichioides mycelium growth is strongly affected by the E.
      guyoniana 20% extract. The phytochemical characterization of the compositions of
      the aqueous extracts has revealed that the presence of some chemical compounds
      (tannins, flavonoids, saponins, steroids, and alkaloids) is likely to be
      responsible for the antifungal activities sought. Conclusion: The antifungal
      properties of A. herba alba, C. cinerea, A. tenuifolius, and E. guyoniana make
      these plants of potential interest for the control of fungi affecting both wheat
      yield and safety.

PMID- 29226146
TI  - Heparanase Inhibition Reduces Glucose Levels, Blood Pressure, and Oxidative
      Stress in Apolipoprotein E Knockout Mice.
AB  - Background: Atherosclerosis is a multifactorial process. Emerging evidence
      highlights a role of the enzyme heparanase in various disease states, including
      atherosclerosis formation and progression. Objective: The aim of the study was to
      investigate the effect of heparanase inhibition on blood pressure, blood glucose
      levels, and oxidative stress in apoE-/- mice. Methods: Male apoE-/- mice were
      divided into two groups: one treated by the heparanase inhibitor PG545,
      administered intraperitoneally weekly for seven weeks, and the other serving as
      control group (injected with saline). Blood pressure was measured a day before
      sacrificing the animals. Serum glucose levels and lipid profile were measured.
      Assessment of oxidative stress was performed as well. Results: PG545
      significantly lowered blood pressure and serum glucose levels in treated mice. It
      also caused significant reduction of the serum oxidative stress. For safety
      concerns, liver enzymes were assessed, and PG545 caused significant elevation
      only of alanine aminotransferase, but not of the other hepatic enzymes.
      Conclusion: Heparanase inhibition by PG545 caused marked reduction of blood
      pressure, serum glucose levels, and oxidative stress in apolipoprotein E
      deficient mice, possibly via direct favorable metabolic and hemodynamic changes
      caused by the inhibitor. Possible hepatotoxic and weight wasting effects are
      subject for future investigation.

PMID- 29226148
TI  - Transition from Deep Regional Blocks toward Deep Nerve Hydrodissection in the
      Upper Body and Torso: Method Description and Results from a Retrospective Chart
      Review of the Analgesic Effect of 5% Dextrose Water as the Primary
      Hydrodissection Injectate to Enhance Safety.
AB  - Deep nerve hydrodissection uses fluid injection under pressure to purposely
      separate nerves from areas of suspected fascial compression, which are
      increasingly viewed as potential perpetuating factors in recalcitrant neuropathic
      pain/complex regional pain. The usage of 5% dextrose water (D5W) as a primary
      injectate for hydrodissection, with or without low dose anesthetic, could limit
      anesthetic-related toxicity. An analgesic effect of 5% dextrose water (D5W) upon
      perineural injection in patients with chronic neuropathic pain has recently been
      described. Here we describe ultrasound-guided methods for hydrodissection of deep
      nerve structures in the upper torso, including the stellate ganglion, brachial
      plexus, cervical nerve roots, and paravertebral spaces. We retrospectively
      reviewed the outcomes of 100 hydrodissection treatments in 26 consecutive cases
      with a neuropathic pain duration of 16 +/- 12.2 months and the mean Numeric Pain
      Rating Scale (NPRS) 0-10 pain level of 8.3 +/- 1.3. The mean percentage of
      analgesia during each treatment session involving D5W injection without
      anesthetic was 88.1%  +/-  9.8%. The pretreatment Numeric Pain Rating Scale score
      of 8.3 +/- 1.3 improved to 1.9 +/- 0.9 at 2 months after the last treatment.
      Patients received 3.8 +/- 2.6 treatments over 9.7 +/- 7.8 months from the first
      treatment to the 2-month posttreatment follow-up. Pain improvement exceeded 50%
      in all cases and 75% in half. Our results confirm the analgesic effect of D5W
      injection and suggest that hydrodissection using D5W provides cumulative pain
      reduction.

PMID- 29226149
TI  - Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid
      Dispersion of Darunavir.
AB  - Objective: The aim of the present study was to improve bioavailability of an
      important antiretroviral drug, Darunavir (DRV), which has low water solubility
      and poor intestinal absorption through solid dispersion (SD) approach
      incorporating polymer with P-glycoprotein inhibitory potential. Methods: A
      statistical approach where design of experiment (DoE) was used to prepare SD of
      DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods
      of preparation, like melt, solvent evaporation, and spray drying method,
      utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized
      SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for
      enhancement in absorption using everted gut sac model, effect of food on
      absorption of DRV, and in vivo prospect. Results and Discussion: DSC, FTIR, XRD,
      and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies
      revealed better absorption of DRV when given with food. Absorption studies and in
      vivo study findings demonstrated great potential of Kolliphor TPGS as P
      glycoprotein inhibitor for increasing intestinal absorption and thus
      bioavailability of DRV. Conclusion: It is concluded that SD of DRV with the
      incorporation of Kolliphor TPGS was potential and promising approach in
      increasing bioavailability of DRV as well as minimizing its extrusion via P
      glycoprotein efflux transporters.

PMID- 29226150
TI  - Transversus Abdominis Plane Block: An Updated Review of Anatomy and Techniques.
AB  - Purpose of Review: Transversus abdominis plane (TAP) block is a regional
      technique for analgesia of the anterolateral abdominal wall. This review
      highlights the nomenclature system and recent advances in TAP block techniques
      and proposes directions for future research. Recent Findings: Ultrasound guidance
      is now considered the gold standard in TAP blocks. It is easy to acquire
      ultrasound images; it can be used in many surgeries involving the anterolateral
      abdominal wall. However, the efficacy of ultrasound-guided TAP blocks is not
      consistent, which might be due to the use of different approaches. The choice of
      technique influences the involved area and block duration. To investigate the
      actual analgesic effects of TAP blocks, we unified the nomenclature system and
      clarified the definition of each technique. Although a single-shot TAP block is
      limited in duration, it is still the candidate of the analgesic standard for
      abdominal wall surgery because the use of the catheter technique and liposomal
      bupivacaine may overcome this limitation. Summary: Ultrasound-guided TAP blocks
      are commonly used. With the unified nomenclature and the development of catheter
      technique and/or liposomal local anesthetics, TAP blocks can be applied more
      appropriately to achieve better pain control.

PMID- 29226151
TI  - In Vitro/In Silico Study on the Role of Doubling Time Heterogeneity among Primary
      Glioblastoma Cell Lines.
AB  - The application of accurate cancer predictive algorithms validated with
      experimental data is a field concerning both basic researchers and clinicians,
      especially regarding a highly aggressive form of cancer, such as Glioblastoma. In
      an aim to enhance prediction accuracy in realistic patient-specific environments,
      accounting for both inter- and intratumoral heterogeneity, we use patient-derived
      Glioblastoma cells from different patients. We focus on cell proliferation using
      in vitro experiments to estimate cell doubling times and sizes for established
      primary Glioblastoma cell lines. A preclinically driven mathematical model
      parametrization is accomplished by taking into account the experimental
      measurements. As a control cell line we use the well-studied U87MG cells. Both in
      vitro and in silico results presented support that the variance between tumor
      staging can be attributed to the differential proliferative capacity of the
      different Glioblastoma cells. More specifically, the intratumoral heterogeneity
      together with the overall proliferation reflected in both the proliferation rate
      and the mechanical cell contact inhibition can predict the in vitro evolution of
      different Glioblastoma cell lines growing under the same conditions. Undoubtedly,
      additional imaging techniques capable of providing spatial information of tumor
      cell physiology and microenvironment will enhance our understanding regarding
      Glioblastoma nature and verify and further improve our predictability.

PMID- 29226152
TI  - The Phytoestrogen Genistein Produces Similar Effects as 17beta-Estradiol on
      Anxiety-Like Behavior in Rats at 12 Weeks after Ovariectomy.
AB  - The phytoestrogen genistein produces anxiolytic-like effects in ovariectomized
      rats, which highlights its potential therapeutic effect in ameliorating anxiety
      in surgical menopausal women. However, no studies have directly compared the
      effects of identical doses of genistein and 17beta-estradiol, the main estrogen
      used in hormone replacement therapy in menopausal women. The present study
      evaluated the anxiolytic-like effects of identical doses of genistein and 17beta
      estradiol (0.045, 0.09, and 0.18 mg/kg/7 days, s.c.) in a surgical menopause
      model in rats in the elevated plus maze and locomotor activity tests at 12 weeks
      after ovariectomy. Additionally, the participation of estrogen receptor-beta in
      the anxiolytic-like effect of genistein and 17beta-estradiol was explored by
      previous administration of the 5 mg/kg tamoxifen antagonist. Genistein and 17beta
      estradiol (0.09 and 0.18 mg/kg) similarly reduced anxiety-like behavior in the
      elevated plus maze and also increased the time spent grooming and rearing,
      without affecting crossing in locomotor activity test. These effects were blocked
      by tamoxifen. Present results indicate that the phytoestrogen genistein has a
      similar behavioral profile as 17beta-estradiol in rats at 12 weeks after
      ovariectomy through action at the estrogen receptor-beta. Thus genistein has
      potential for reducing anxiety-like behavior associated with low concentrations
      of ovarian hormones, which normally occurs during natural and surgical menopause.

PMID- 29226153
TI  - The Exercise-Induced Irisin Is Associated with Improved Levels of Glucose
      Homeostasis Markers in Pregnant Women Participating in 8-Week Prenatal Group
      Fitness Program: A Pilot Study.
AB  - Background: Both exercise and pregnancy influence serum irisin concentration.
      Aim: To determine how the interaction of pregnancy and exercise affects irisin
      level and whether various patterns of exercise adherence had different effect on
      irisin concentration. Methods: It was a one-group pretest-posttest study among 9
      Caucasian nulliparous healthy women in normal pregnancy (age 23 +/- 3 years, 21
      +/- 2 weeks of gestation; mean +/- SD) who participated in 8-week group fitness
      program. Before and after exercise intervention, we determined serum
      concentrations of irisin and selected parameters of lipid profile and glucose
      homeostasis markers. Results: In active women, irisin slightly decreased with the
      development of pregnancy. After 8 weeks of exercising, irisin correlated
      negatively with fasting glucose (R = -0.922; p = 0.001), glycated hemoglobin (R =
      -0.784; p = 0.012), and insulin concentrations (R = -0.845; p = 0.004). In women
      exercising below recommended level, we observed a significant drop in irisin
      concentration, whereas in women exercising at least three times a week this
      myokine slightly increased (31% difference; 90% confidence limits +/-28; a large,
      clear effect). Conclusions: Irisin stimulated by prenatal exercise may improve
      glucose homeostasis markers in healthy women and compensate for metabolic changes
      induced by pregnancy. Moreover, the frequency of exercise may regulate the
      changes in exercise-induced irisin concentration.

PMID- 29226154
TI  - Reduced Transferrin Levels in Active Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease (IBD) is an inflammatory disease of unclear
      etiopathogenesis and challenging diagnosis, frequently complicated by anemia and
      malnutrition. C-reactive protein (CRP) remains the only biochemical marker of
      clinical relevance. The aim of this study was to test hypothesis that
      transferrin, coinfluenced by inflammation, malnutrition, anemia, and oxidative
      stress, may better reflect global IBD patient's condition than any other more
      specific index. Transferrin and other indices of inflammation, anemia,
      malnutrition, and oxidative stress were measured in 137 IBD patients (Crohn's
      disease (CD): n = 63 and ulcerative colitis (UC): n = 74) and 97 controls.
      Transferrin is reduced in active CD and UC and negatively correlates with the
      disease activity scores (CD: rho = -0.49; UC: rho = -0.52). In UC, transferrin
      correlates negatively with CRP, erythrocyte sedimentation rate (ESR), leukocytes,
      platelets, interleukin-6, interleukin-10, and TNF-alpha and positively with
      albumins, cholesterol, hemoglobin, hematocrit, erythrocytes, iron, and
      paraoxonase-1. In CD, transferrin correlates negatively with CRP, leukocytes,
      platelets, interleukin-1, and interleukin-6 and positively with albumins, iron,
      catalase, glutathione peroxidase-1, superoxide dismutase-1, and paraoxonase-1.
      The associations with inflammation and anemia/malnutrition were more pronounced
      in UC and with oxidative stress in CD. As UC activity marker, transferrin
      outperforms ESR and hemoglobin, indices used in calculating the disease clinical
      severity score.

PMID- 29226155
TI  - Views and Experiences of New Zealand Women with Gestational Diabetes in Achieving
      Glycaemic Control Targets: The Views Study.
AB  - Introduction: Optimal glycaemic control in women with gestational diabetes
      mellitus (GDM) reduces maternal and infant morbidity. Method: A survey was
      administered to women diagnosed with GDM to explore their views and experiences
      in achieving optimal glycaemic control. Results: Sixty women participated.
      Enablers included being taught to test capillary blood glucose in group settings
      where the health professional demonstrated this on themselves first (60, 100%);
      health professionals listening (41, 68%); being reminded to perform blood glucose
      testing (33, 55%); and being provided healthy meals by friends and family (28,
      47%). Barriers included not having information in a woman's first language (33,
      55%); being offered unhealthy food (19, 31%); not being believed by health
      professionals (13, 21%); receiving inconsistent information by health
      professionals (10, 16%); never being seen twice by the same health professional
      (8, 13%); and long waiting hours at clinics (7, 11%). Two-thirds of women (37,
      62%) reported that food costs were not a barrier, but that they were always or
      frequently hungry. Conclusion: Optimising experiences for women with GDM for
      achieving glycaemic control and overcoming barriers, regardless of glycaemic
      targets, requires further focus on providing meaningful health literacy and
      support from health professionals, family, friends, and work colleagues.

PMID- 29226158
TI  - Corrigendum to "The Controversial C5a Receptor C5aR2: Its Role in Health and
      Disease".
AB  - [This corrects the article DOI: 10.1155/2017/8193932.].

PMID- 29226156
TI  - MicroRNAs Regulate Thymic Epithelium in Age-Related Thymic Involution via Down-
      or Upregulation of Transcription Factors.
AB  - Age-related thymic involution is primarily induced by defects in nonhematopoietic
      thymic epithelial cells (TECs). It is characterized by dysfunction of multiple
      transcription factors (TFs), such as p63 and FoxN1, and also involves other TEC
      associated regulators, such as Aire. These TFs and regulators are controlled by
      complicated regulatory networks, in which microRNAs (miRNAs) act as a key player.
      miRNAs can either directly target the 3'-UTRs (untranslated regions) of the TFs
      to suppress TF expression or target TF inhibitors to reduce or increase TF
      inhibitor expression and thereby indirectly enhance or inhibit TF expression.
      Here, we review the current understanding and recent studies about how miRNAs are
      involved in age-related thymic involution via regulation of TEC-autonomous TFs.
      We also discuss potential strategies for targeting miRNAs to rejuvenate age
      related declined thymic function.

PMID- 29226157
TI  - Fas-Related Apoptosis of Peritoneal Fluid Macrophages in Endometriosis Patients:
      Understanding the Disease.
AB  - Recent studies of the peritoneal cavity environment in endometriosis demonstrate
      quantitative and qualitative changes in the cells responsible for cell-mediated
      immunity. Such changes may have led to disturbances in the surveillance,
      recognition, and destruction of misplaced endometrial cells and might have, in
      fact, brought about the disease. The aim of the study was to assess CD95 (Fas)
      expression on (activated) peritoneal fluid (PF) macrophages, as well as to
      ascertain soluble Fas (sFas) concentration in the PF of endometriosis patients,
      as compared to the nonendometriotic group. The concentration of leukocytes in the
      PF, the percentage of cells expressing CD45+/CD14+, and the percentage of PF
      macrophages expressing the HLA-DR antigen were significantly higher in patients
      with stages I and II endometriosis. The percentage of Fas- (CD95+-) expressing
      macrophages was significantly higher in all stages of the disease, in comparison
      with controls. Moreover, the concentration of sFas in the PF of patients with
      moderate and severe endometriosis was significantly higher, as compared to the
      reference group. The high number of immune cells in PF in early stage
      endometriosis and their increased susceptibility to apoptosis confirm the role of
      the impaired peritoneal environment and immune defects in the development and
      progression of the disease.

PMID- 29226159
TI  - Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions.
AB  - Diagnosis of severe cutaneous adverse drug reactions should involve
      immunohistopathological examination, which gives insight into the pathomechanisms
      of these disorders. The characteristic histological findings of erythema
      multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis
      (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished
      from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte
      necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity
      syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic
      symptoms (DRESS) each display a variety of histopathological findings, which may
      partly correlate with the clinical manifestations. Although the histopathology of
      DRESS is nonspecific, the association of two or more of the four patterns
      eczematous changes, interface dermatitis, acute generalized exanthematous
      pustulosis- (AGEP-) like patterns, and EM-like patterns-might appear in a single
      biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of
      DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP
      typically shows spongiform superficial epidermal pustules accompanied with edema
      of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in
      IL36RN may have a definite effect on pathological similarities between AGEP and
      generalized pustular psoriasis.

PMID- 29226160
TI  - The significance of changes in platelet concentration during the early phase
      after severe burn injury in a Chinese mass casualty.
AB  - Background: Changes in platelet concentration are common in severe burn patients.
      Platelets play a key role in the course of disease. This study aims to explore
      the significance of platelet concentration during the course of the disease in
      victims of a mass burn casualty. Methods: A total of 180 patients were involved
      in the "8.2" Kunshan explosion accident in China. The examined data included age,
      gender, total burn area (% TBSA), third-degree burn area (% TBSA), and platelet
      concentration within the first 5 days after the burn injury. The patients were
      divided into two groups according to four indicators (resuscitation, acute
      respiratory distress syndrome, acute kidney injury, septic shock). We collected
      several types of data for the patients and divided the patients into a
      complication group and non-complication group according to the diagnostic
      criteria. We analyzed the platelet concentration of the two groups using t tests
      to determine whether significant differences were present. P values < 0.05 were
      considered statistically significant. Results: The group with successful
      resuscitation had higher platelet concentration than the failure group on day 3
      and day 5. The patients who suffered from acute kidney injury (AKI) and septic
      shock had a lower platelet concentration than non-sufferers on day 3 and day 5.
      Conclusions: The platelet concentration of burn patients can dynamically reflect
      the pathophysiological changes of the body. It can be used as an early objective
      indicator of prognosis in mass burn casualty cases.

PMID- 29226161
TI  - Multiple Imputation in Two-Stage Cluster Samples Using The Weighted Finite
      Population Bayesian Bootstrap.
AB  - Multistage sampling is often employed in survey samples for cost and convenience.
      However, accounting for clustering features when generating datasets for multiple
      imputation is a nontrivial task, particularly when, as is often the case, cluster
      sampling is accompanied by unequal probabilities of selection, necessitating case
      weights. Thus, multiple imputation often ignores complex sample designs and
      assumes simple random sampling when generating imputations, even though failing
      to account for complex sample design features is known to yield biased estimates
      and confidence intervals that have incorrect nominal coverage. In this article,
      we extend a recently developed, weighted, finite-population Bayesian bootstrap
      procedure to generate synthetic populations conditional on complex sample design
      data that can be treated as simple random samples at the imputation stage,
      obviating the need to directly model design features for imputation. We develop
      two forms of this method: one where the probabilities of selection are known at
      the first and second stages of the design, and the other, more common in public
      use files, where only the final weight based on the product of the two
      probabilities is known. We show that this method has advantages in terms of bias,
      mean square error, and coverage properties over methods where sample designs are
      ignored, with little loss in efficiency, even when compared with correct fully
      parametric models. An application is made using the National Automotive Sampling
      System Crashworthiness Data System, a multistage, unequal probability sample of
      U.S. passenger vehicle crashes, which suffers from a substantial amount of
      missing data in "Delta-V," a key crash severity measure.

PMID- 29226162
TI  - Relationship Between Age at Onset of Symptoms and Intraoperative Findings in Hip
      Arthroscopic Surgery.
AB  - Background: Hip arthroscopic surgery is intended to treat multiple abnormalities
      in an effort to delay the progression to osteoarthritis, especially in young
      patients. However, the length of time in which patients experience joint pain
      before seeking a specialist for a diagnosis can delay hip preservation surgery
      and influence clinical outcomes. Purpose: To investigate the relationship between
      age at symptom onset and findings during hip arthroscopic surgery as well as
      outcomes after 2 years of clinical follow-up. Study Design: Cohort study; Level
      of evidence, 3. Methods: From February 2008 to March 2015, data were
      prospectively collected on all patients undergoing hip arthroscopic surgery at a
      single institution. Anatomic and pathological characteristics were recorded
      intraoperatively. The mean age at onset of symptoms was calculated and correlated
      with intraoperative findings using Pearson correlation and logistic regression.
      All patients were assessed preoperatively and postoperatively with 4 patient
      reported outcome measures: the modified Harris Hip Score (mHHS), the Non
      Arthritic Hip Score (NAHS), the Hip Outcome Score-Activities of Daily Living (HOS
      ADL), and the Hip Outcome Score-Sport-Specific Subscale (HOS-SSS). Pain was
      estimated using a visual analog scale (VAS). Furthermore, patients with an age at
      onset of symptoms below the mean (34.6 years) were compared with those of an age
      at onset of symptoms above the mean. The 2 groups were compared using the Student
      t test and the chi-square test. P values <.05 were considered significant.
      Results: A total of 1697 patients met the inclusion criteria. Body mass index was
      weakly correlated with age (r = 0.3). Younger patients had a lower prevalence of
      combined Seldes type 1 and 2 labral tears; acetabular labrum articular disruption
      (ALAD) grade 2, 3, and 4 acetabular chondral lesions; and Outerbridge grade 2, 3,
      and 4 femoral head chondral lesions (P < .05 for all). More advanced age was
      correlated with wider labral tears and chondral lesions based on a clock face (r
      >= 0.2, P < .05). Patients younger than 34.6 years had a lower prevalence of
      gluteus medius and ligamentum teres tears (P <= .001). The prevalence of
      synovitis was positively correlated with age, while instability was negatively
      correlated with age (P = .04). The improvement of scores from preoperatively to 2
      year follow-up in the younger patient group was 62.69 to 83.82 for the mHHS,
      64.97 to 87.35 for the HOS-ADL, 43.46 to 73.37 for the HOS-SSS, 63.01 to 85.19
      for the NAHS, and 5.61 to 2.53 for pain VAS. All score improvements were
      statistically significant (P < .001). Regarding the older patient group, the
      improvement of scores from preoperatively to 2-year follow-up was 58.55 to 78.27
      for the mHHS, 57.59 to 79.66 for the HOS-ADL, 35.63 to 61.88 for the HOS-SSS,
      55.28 to 77.55 for the NAHS, and 5.72 to 3.01 for pain VAS. All score
      improvements were statistically significant (P < .001). Conclusion: Of the
      multiple intraoperative findings in hip arthroscopic surgery, many are related to
      age at onset of symptoms. Although we found a statistically significant
      improvement in clinical outcomes in both groups after 2-year follow-up,
      apparently the less complex and smaller lesions observed in both the articular
      cartilage and the labrum of younger patients result in better outcomes compared
      with older patients.

PMID- 29226163
TI  - Diagnostic Accuracy of 3 Physical Examination Tests in the Assessment of Hip
      Microinstability.
AB  - Background: Hip microinstability is a diagnosis gaining increasing interest.
      Physical examination tests to identify microinstability have not been objectively
      investigated using intraoperative confirmation of instability as a reference
      standard. Purpose: To determine the test characteristics and diagnostic accuracy
      of 3 physical examination maneuvers in the detection of hip microinstability.
      Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A review
      was conducted of 194 consecutive hip arthroscopic procedures performed by a
      sports medicine surgeon at a tertiary-care academic center. Physical examination
      findings of interest, including the abduction-hyperextension-external rotation
      (AB-HEER) test, the prone instability test, and the hyperextension-external
      rotation (HEER) test, were obtained from prospectively collected data. The
      reference standard was intraoperative identification of instability based on
      previously published objective criteria. Test characteristics, including
      sensitivity, specificity, positive and negative predictive values, and accuracy,
      were calculated for each test as well as for combinations of tests. Results: A
      total of 109 patients were included in the analysis. The AB-HEER test was most
      accurate, with a sensitivity of 80.6% (95% CI, 70.8%-90.5%) and a specificity of
      89.4% (95% CI, 80.5%-98.2%). The prone instability test had a low sensitivity
      (33.9%) but a very high specificity (97.9%). The HEER test performed second in
      both sensitivity (71.0%) and specificity (85.1%). The combination of multiple
      tests with positive findings did not yield significantly greater accuracy. All
      tests had high positive predictive values (range, 86.3%-95.5%) and moderate
      negative predictive values (range, 52.9%-77.8%). When all 3 tests had positive
      findings, there was a 95.0% (95% CI, 90.1%-99.9%) chance that the patient had
      microinstability. Conclusion: The AB-HEER test most accurately predicted hip
      instability, followed by the HEER test and the prone instability test. However,
      the high specificity of the prone instability test makes it a useful test to
      "rule in" abnormalities. A positive result from any test predicted hip
      instability in 86.3% to 90.9% of patients, but a negative test result did not
      conclusively rule out hip instability, and other measures should be considered in
      making the diagnosis. The use of these tests may aid the clinician in diagnosing
      hip instability, which has been considered a difficult diagnosis to make because
      of its dynamic nature.

PMID- 29226164
TI  - Short-term Outcomes Following Concussion in the NFL: A Study of Player Longevity,
      Performance, and Financial Loss.
AB  - Background: A short-term protocol for evaluation of National Football League
      (NFL) athletes incurring concussion has yet to be fully defined and framed in the
      context of the short-term potential team and career longevity, financial risk,
      and performance. Purpose: To compare the short-term career outcomes for NFL
      players with concussions by analyzing the effect of concussions on (1) franchise
      release rate, (2) career length, (3) salary, and (4) performance. Study Design:
      Cohort study; Level of evidence, 3. Methods: NFL player transaction records and
      publicly available injury reports from August 2005 to January 2016 were analyzed.
      All players sustaining documented concussions were evaluated for a change to
      inactive or DNP ("did not participate") status. A case-control design compared
      franchise release rates and remaining NFL career span. Career length was analyzed
      via survival analysis. Salary and performance differences were analyzed with
      publicly available contract data and a performance-scoring algorithm based on
      position/player level. Results: Of the 5894 eligible NFL players over the 11-year
      period, 307 sustained publicly reported concussions resulting in the DNP injury
      protocol. Analysis of the probability of remaining in the league demonstrated a
      statistically significantly shorter career length for the concussion group at 3
      and 5 years after concussion. The year-over-year change in contract value for the
      concussion group resulted in a mean overall salary reduction of $300,000 +/-
      $1,300,000 per year (interquartile range, -$723,000 to $450,000 per year). The
      performance score reduction for all offensive scoring players sustaining
      concussions was statistically significant. Conclusion: This retrospective study
      demonstrated that NFL players who sustain a concussion face a higher overall
      franchise release rate and shorter career span. Players who sustained concussions
      may incur significant salary reductions and perform worse after concussion. Short
      term reductions in longevity, performance, and salary after concussion exist and
      deserve additional consideration.

PMID- 29226165
TI  - Game Schedules and Rate of Concussions in the National Football League.
AB  - Background: Concussion prevention in the National Football League (NFL) is an
      important priority for player safety. The NFL now has modified game schedules,
      and one concern is that unconventional game schedules, such as a shortened rest
      period due to playing on a Thursday rather than during the weekend, may lead to
      an increased risk of injuries. Hypothesis: Unconventional game schedules in the
      NFL are associated with an increased rate of concussion. Study Design:
      Descriptive epidemiological study. Methods: This study analyzed concussions and
      game schedules over the NFL regular seasons from 2012 to 2015 (4 years).
      Documented numbers of concussions, identified by use of the online database PBS
      Frontline Concussion Watch, were summarized by regular-season weeks. Association
      of days of rest and game location (home, away, or overseas) with the rate of
      concussion was examined by use of the chi2 test. Logistic regression analysis was
      performed to examine the relationships of days of rest and home/away games to the
      risk of repeated concussions, with adjustment for player position. Results: A
      total of 582 concussions were analyzed in this study. A significantly greater
      number of concussions occurred in the second half of the season (P < .01). No
      significant association was found between the rate of concussion and the days of
      rest, game location, or timing of the bye week by the team or the opponent (P >
      .05). Game schedules were not significantly associated with the occurrence of
      repeat concussions (P > .05). Conclusion: Unconventional game schedules in the
      NFL, including playing on Thursday and playing overseas, do not seem to put
      players at increased risk of concussions.

PMID- 29226166
TI  - A Radiographic Healing Classification for Osteochondritis Dissecans of the Knee
      Provides Good Interobserver Reliability.
AB  - Background: Recent studies have examined radiographic factors associated with
      healing of osteochondritis dissecans (OCD) lesions of the knee. However, there is
      still no gold standard in determining the healing status of an OCD lesion.
      Purpose: We examined temporally associated patterns of healing to (1) evaluate
      the practicality of a classification system and (2) elucidate any associations
      between healing pattern and patient age, sex, lesion location, treatment type,
      and physeal patency. Study Design: Cohort study (diagnosis); Level of evidence,
      3. Methods: We retrospectively screened 489 patients from 2006 to 2010 for a
      total of 41 consecutive knee OCD lesions that met inclusion criteria, including
      at least 3 consecutive radiographic series (mean patient age, 12.8 years; range,
      7.8-17.1 years; mean follow-up, 75.1 weeks). Radiographs were arranged in
      sequential order for ratings by 2 orthopaedic sports medicine specialists.
      Healing patterns were rated as boundary resolution, increasing radiodensity of
      progeny fragment, combined, or not applicable. Repeat ratings were conducted 3
      weeks later. Results: Patients were most commonly adolescent males aged 13 to 17
      years, with a medial femoral condyle lesion that was treated operatively.
      Interobserver reliability of the healing classification was good (intraclass
      correlation coefficient, 0.67; 95% CI, 0.55-0.79). Boundary and radiodensity
      healing was observed for all ages, sexes, lesion locations, treatment types, and
      physeal patency states. Conclusion: This study evaluated a valuable radiographic
      paradigm-boundary resolution, increasing radiodensity of progeny fragment, or
      combined-for assessment of OCD lesion healing. The proposed system of healing
      classification demonstrated good inter- and intraobserver reliability. Healing
      patterns were not significantly associated with any particular age, sex, lesion
      location, treatment type, or physeal patency status. The development of a
      classification system for knee OCD may eventually improve clinical assessment and
      management of OCD lesions.

PMID- 29226167
TI  - Mathematical Modeling of "Chronic" Infectious Diseases: Unpacking the Black Box.
AB  - Background: Mathematical models are increasingly used to understand the dynamics
      of infectious diseases, including "chronic" infections with long generation
      times. Such models include features that are obscure to most clinicians and
      decision-makers. Methods: Using a model of a hypothetical active case-finding
      intervention for tuberculosis in India as an example, we illustrate the effects
      on model results of different choices for model structure, input parameters, and
      calibration process. Results: Using the same underlying data, different
      transmission models produced different estimates of the projected intervention
      impact on tuberculosis incidence by 2030 with different corresponding uncertainty
      ranges. We illustrate the reasons for these differences and present a simple
      guide for clinicians and decision-makers to evaluate models of infectious
      diseases. Conclusions: Mathematical models of chronic infectious diseases must be
      understood to properly inform policy decisions. Improved communication between
      modelers and consumers is critical if model results are to improve the health of
      populations.

PMID- 29226168
TI  - Risks of Ruxolitinib in STAT1 Gain-of-Function-Associated Severe Fungal Disease.
AB  - Heterozygous STAT1 gain-of-function (GOF) mutations are associated with chronic
      mucocutaneous candidiasis and a broad spectrum of infectious, inflammatory, and
      vascular manifestations. We describe therapeutic failures with the Janus Kinase
      (JAK) inhibitor ruxolitinib in 2 STAT1 GOF patients with severe invasive or
      cutaneous fungal infections.

PMID- 29226169
TI  - Prolonged Detection of Japanese Encephalitis Virus in Urine and Whole Blood in a
      Returned Short-term Traveler.
AB  - We describe a fatal case of Japanese encephalitis virus infection following short
      term travel to Thailand. Viral RNA was detected in urine and whole blood out to
      26 and 28 days, respectively, after the onset of symptoms. Live virus was
      isolated from a urine specimen from day 14.

PMID- 29226170
TI  - Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A
      Systematic Review and Meta-analysis.
AB  - Background: Mismanagement of asymptomatic patients with positive urine cultures
      (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes
      antimicrobial resistance and results in unnecessary antimicrobial-related adverse
      events and increased health care costs. Methods: We conducted a systematic review
      and meta-analysis of studies that reported on the rate of inappropriate ASB
      treatment published from 2004 to August 2016. The appropriateness of
      antimicrobial administration was based on guidelines published by the Infectious
      Diseases Society of America. Results: A total of 2142 nonduplicate articles were
      identified, and among them 30 fulfilled our inclusion criteria. The pooled
      prevalence of antimicrobial treatment among 4129 cases who did not require
      treatment was 45% (95% CI, 39-50). Isolation of gram-negative pathogens (odds
      ratio [OR], 3.58; 95% CI, 2.12-6.06), pyuria (OR, 2.83; 95% CI, 1.9-4.22),
      nitrite positivity (OR, 3.83; 95% CI, 2.24-6.54), and female sex (OR, 2.11; 95%
      CI, 1.46-3.06) increased the odds of receiving treatment. The rates of treatment
      were higher in studies with >=100 000 cfu/mL cutoff values compared with <10 000
      cfu/mL for bacterial growth (P, .011). The implementation of educational and
      organizational interventions designed to eliminate the overtreatment of ASB
      resulted in a median absolute risk reduction of 33% (rangeARR, 16-36%, medianRRR,
      53%; rangeRRR, 25-80%). Conclusion: The mismanagement of ASB remains extremely
      frequent. Female sex and the overinterpretation of certain laboratory data
      (positive nitrites, pyuria, isolation of gram-negative bacteria and cultures with
      higher microbial count) are associated with overtreatment. Even simple
      stewardship interventions can be particularly effective, and antimicrobial
      stewardship programs should focus on the challenge of differentiating true
      urinary tract infection from ASB.

PMID- 29226171
TI  - Antimicrobial Resistance of Sterile Site Infections in Sub-Saharan Africa: A
      Systematic Review.
AB  - Sparse data exist from sub-Saharan Africa (SSA) on the prevalence of
      antimicrobial resistance (AMR). A prior review of antimicrobial resistance in SSA
      from 1990 to 2013 showed a high prevalence of AMR to commonly used antibiotics in
      this setting. We reviewed the literature published since 2013. Four databases
      (PubMed, EMBASE, Cochrane, and African Journals Online) were searched for
      articles between February 2013 and March 2016 with a focus on sterile site
      infections (bacteremia, urinary tract infections [UTIs], and meningitis). We
      focused on the original World Health Organization-identified priority pathogens
      and antibiotics, prior to the release of the most recently updated and expanded
      list in 2017. There were 19 eligible studies: bacteremia (12), UTI (6), and
      meningitis (1). Eight studies were from Western and Central Africa, 8 from
      Eastern Africa, and 4 from Southern Africa. Prevalence of Escherichia coli
      resistance to third-generation cephalosporins ranged from 0% to 75%. No studies
      reported resistance to carbapenems among Klebsiella spp. Prevalence of
      fluoroquinolone resistance ranged from 8.3% to 100% among E. coli and 0% to 15%
      among Salmonella spp. Prevalence of resistance to penicillin among Streptococcus
      pneumoniae isolates ranged from 25% to 100%. Testing for extended-spectrum beta
      lactamase was reported in 7 studies (range, 1.3-60% among tested isolates).
      Methods for evaluating AMR varied across studies; standardized approaches are
      needed in the region. Testing for mechanisms of resistance is low even in
      research settings, but important mechanisms of resistance such as ESBL production
      are present.

PMID- 29226172
TI  - Enteric Microbiome Markers as Early Predictors of Clinical Outcome in Allogeneic
      Hematopoietic Stem Cell Transplant: Results of a Prospective Study in Adult
      Patients.
AB  - Background: Infections and graft-vs-host disease (GvHD) still represent major,
      not easily predictable complications in allogeneic hematopoietic stem cell
      transplant (allo-HSCT). Both conditions have been correlated to altered enteric
      microbiome profiles during the peritransplant period. The main objective of this
      study was to identify possible early microbiome-based markers useful in
      pretransplant risk stratification. Methods: Stool samples were collected from 96
      consecutive patients at the beginning of the pretransplant conditioning regimen
      (T0) and at 10 (T1) and 30 (T2) days following transplant. When significant in
      univariate analysis, the identified microbiome markers were used in multivariate
      regression analyses, together with other significant clinical variables for allo
      HSCT-related risk stratification. Four main outcomes were addressed: (1) septic
      complications, (2) GvHD, (3) relapse of the underlying disease, and (4)
      mortality. Results: The presence of >5% proinflammatory Enterobacteriaceae at T0
      was the only significant marker for the risk of microbiologically confirmed
      sepsis. Moreover, <=10% Lachnospiraceae at T0 was the only significant factor for
      increased risk of overall mortality, including death from both infectious and
      noninfectious causes.Finally, a low bacterial alpha-diversity (Shannon index <=
      1.3) at T1 was the only variable significantly correlating with an increased risk
      of GvHD within 30 days. Conclusions: Microbiome markers can be useful in the very
      early identification of patients at risk for major transplant-related
      complications, offering new tools for individualized preemptive or therapeutic
      strategies to improve allo-HSCT outcomes.

PMID- 29226173
TI  - Long-term Outcome of Antiretroviral Treatment in Patients With and Without
      Concomitant Tuberculosis Receiving Health Center-Based Care-Results From a
      Prospective Cohort Study.
AB  - Background: In order to increase treatment coverage, antiretroviral treatment
      (ART) is provided through primary health care in low-income high-burden
      countries, where tuberculosis (TB) co-infection is common. We investigated the
      long-term outcome of health center-based ART, with regard to concomitant TB.
      Methods: ART-naive adults were included in a prospective cohort at Ethiopian
      health centers and followed for up to 4 years after starting ART. All
      participants were investigated for active TB at inclusion. The primary study
      outcomes were the impact of concomitant TB on all-cause mortality, loss to follow
      up (LTFU), and lack of virological suppression (VS). Kaplan-Meier survival
      estimates and Cox proportional hazards models with multivariate adjustments were
      used. Results: In total, 141/729 (19%) subjects had concomitant TB, 85% with
      bacteriological confirmation (median CD4 count TB, 169 cells/mm3; IQR, 99-265;
      non-TB, 194 cells/mm3; IQR, 122-275). During follow-up (median, 2.5 years), 60
      (8%) died and 58 (8%) were LTFU. After >=6 months of ART, 131/630 (21%) had lack
      of VS. Concomitant TB did not influence the rates of death, LTFU, or VS. Male
      gender and malnutrition were associated with higher risk of adverse outcomes.
      Regardless of TB co-infection status, even after 3 years of ART, two-thirds of
      participants had CD4 counts below 500 cells/mm3. Conclusions: Concomitant TB did
      not impact treatment outcomes in adults investigated for active TB before
      starting ART at Ethiopian health centers. However, one-third of patients had
      unsatisfactory long-term treatment outcomes and immunologic recovery was slow,
      illustrating the need for new interventions to optimize ART programs.

PMID- 29226174
TI  - Proprotein Convertase Subtilisin/Kexin 9 Levels in Relation to Systemic Immune
      Activation and Subclinical Coronary Plaque in HIV.
AB  - Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is known to mediate
      homeostasis of low-density lipoprotein cholesterol (LDL-c), but it may also
      participate in immune reactivity and atherogenesis. Methods: We compared
      circulating PCSK9 levels among asymptomatic individuals with and without HIV.
      Further, within each group, we assessed the relationship between PCSK9 levels,
      traditional cardiovascular disease risk factors, immune activation, and
      subclinical coronary atherosclerotic plaque. Results: PCSK9 levels were higher
      among HIV-infected (n = 149) vs matched non-HIV-infected subjects (n = 69; 332
      [272, 412] ng/mL vs 304 [257, 375] ng/mL; P = .047). Among HIV-infected subjects,
      significant albeit modest positive associations were noted between PCSK9 levels
      and markers of systemic monocyte activation including sCD14 (rho = 0.22; P =
      .009) and sCD163 (rho = 0.23; P = .006). In this group, PCSK9 levels related
      weakly to LDL-c (rho = 0.16; P = .05) and also to Framingham Point Score but did
      not relate to subclinical coronary atherosclerotic plaque parameters.
      Conclusions: Among HIV-infected individuals, circulating PCSK9 levels are
      elevated and related to systemic markers of monocyte activation but not to
      coronary plaque parameters. Additional studies are needed to determine the
      effects of PCSK9 on immune activation and atherogenesis in HIV and to assess
      whether PCSK9 inhibition reduces immune activation and coronary atherosclerotic
      plaque burden. Clinical Trial Registration: NCT00455793.

PMID- 29226175
TI  - Longitudinal, transcranial measurement of functional activation in the rat brain
      by diffuse correlation spectroscopy.
AB  - Neural activity is an important biomarker for the presence of neurodegenerative
      diseases, cerebrovascular alterations, and brain trauma; furthermore, it is a
      surrogate marker for treatment effects. These pathologies may occur and evolve in
      a long time-period, thus, noninvasive, transcutaneous techniques are necessary to
      allow a longitudinal follow-up. In the present work, we have customized
      noninvasive, transcutaneous, diffuse correlation spectroscopy (DCS) to localize
      changes in cerebral blood flow (CBF) induced by neural activity. We were able to
      detect changes in CBF in the somatosensory cortex by using a model of electrical
      forepaw stimulation in rats. The suitability of DCS measurements for longitudinal
      monitoring was demonstrated by performing multiple sessions with the same animals
      at different ages (from 6 to 18 months). In addition, functional DCS has been
      cross-validated by comparison with functional magnetic resonance imaging (fMRI)
      in the same animals in a subset of the time-points. The overall results obtained
      with transcutaneous DCS demonstrates that it can be utilized in longitudinal
      studies safely and reproducibly to locate changes in CBF induced by neural
      activity in the small animal brain.

PMID- 29226176
TI  - Holistic segmentation of the lung in cine MRI.
AB  - Duchenne muscular dystrophy (DMD) is a childhood-onset neuromuscular disease that
      results in the degeneration of muscle, starting in the extremities, before
      progressing to more vital areas, such as the lungs. Respiratory failure and
      pneumonia due to respiratory muscle weakness lead to hospitalization and early
      mortality. However, tracking the disease in this region can be difficult, as
      current methods are based on breathing tests and are incapable of distinguishing
      between muscle involvements. Cine MRI scans give insight into respiratory muscle
      movements, but the images suffer due to low spatial resolution and poor signal-to
      noise ratio. Thus, a robust lung segmentation method is required for accurate
      analysis of the lung and respiratory muscle movement. We deployed a deep learning
      approach that utilizes sequence-specific prior information to assist the
      segmentation of lung in cine MRI. More specifically, we adopt a holistically
      nested network to conduct image-to-image holistic training and prediction. One
      frame of the cine MRI is used in the training and applied to the remainder of the
      sequence ([Formula: see text] frames). We applied this method to cine MRIs of the
      lung in the axial, sagittal, and coronal planes. Characteristic lung motion
      patterns during the breathing cycle were then derived from the segmentations and
      used for diagnosis. Our data set consisted of 31 young boys, age [Formula: see
      text] years, 15 of whom suffered from DMD. The remaining 16 subjects were age
      matched healthy volunteers. For validation, slices from inspiratory and
      expiratory cycles were manually segmented and compared with results obtained from
      our method. The Dice similarity coefficient for the deep learning-based method
      was [Formula: see text] for the sagittal view, [Formula: see text] for the axial
      view, and [Formula: see text] for the coronal view. The holistic neural network
      approach was compared with an approach using Demon's registration and showed
      superior performance. These results suggest that the deep learning-based method
      reliably and accurately segments the lung across the breathing cycle.

PMID- 29226178
TI  - In vitro Analysis for Macrophage Binding and Pro-inflammatory Responses to
      Candida albicans.
AB  - Macrophage recognition of Candida albicans (C. albicans) is facilitated by
      pattern recognition receptors that interact with the fungal pathogen associated
      molecular patterns (PAMPs). Dectin-1 is the major macrophage receptor that is
      known to recognize fungal Beta-glucans leading to induction of various immune
      responses. This receptor is also known to be required for in vivo protection
      against C. albicans (Taylor et al., 2007). We recently showed that the Dectin-1
      mediated protection in vivo is strain-dependent, and that C. albicans can adapt
      to modulate immune recognition by Dectin-1 (Marakalala et al., 2013). In vitro
      analysis, however, showed a Dectin-1-dependent and pro-inflammatory responses
      against all strains tested. This protocol describes in detail the in vitro
      analysis used in the paper. In particular, methods involved in fluorescent
      labeling of live C. albicans, quantification of macrophage binding of the
      pathogen, and pro-inflammatory responses to yeast and hyphal forms of the fungi
      are described.

PMID- 29226177
TI  - Color discrimination errors associate with axial motor impairments in Parkinson's
      disease.
AB  - Background: Visual function deficits are more common in imbalance-predominant
      compared to tremor-predominant PD suggesting a pathophysiological role of
      impaired visual functions in axial motor impairments. Objective: To investigate
      the relationship between changes in color discrimination and motor impairments in
      PD while accounting for cognitive or other confounder factors. Methods: PD
      subjects (n=49, age 66.7+/-8.3 years; Hoehn & Yahr stage 2.6+/-0.6) completed
      color discrimination assessment using the Farnsworth-Munsell 100 Hue Color Vision
      Test, neuropsychological, motor assessments and [11C]dihydrotetrabenazine
      vesicular monoamine transporter type 2 PET imaging. MDS-UPDRS sub-scores for
      cardinal motor features were computed. Timed up and go mobility and walking tests
      were assessed in 48 subjects. Results: Bivariate correlation coefficients between
      color discrimination and motor variables were significant only for the Timed up
      and go (RS=0.44, P=0.0018) and the MDS-UPDRS axial motor scores (RS=0.38,
      P=0.0068). Multiple regression confounder analysis using the Timed up and go as
      outcome parameter showed a significant total model (F(5,43)= 7.3, P<0.0001) with
      significant regressor effects for color discrimination (standardized beta=0.32,
      t=2.6, P=0.012), global cognitive Z-score (beta=-0.33, t=-2.5, P=0.018), duration
      of disease (beta=0.26, t=1.8, P=0.038), but not for age or striatal dopaminergic
      binding. The color discrimination test was also a significant independent
      regressor in the MDS-UPDRS axial motor model (standardized beta=0.29, t=2.4,
      P=0.022; total model t(5,43)= 6.4, P=0.0002). Conclusions: Color discrimination
      errors associate with axial motor features in PD independent of cognitive
      deficits, nigrostriatal dopaminergic denervation, and other confounder variables.
      These findings may reflect shared pathophysiology between color discrimination
      visual impairments and axial motor burden in PD.

PMID- 29226179
TI  - Virus Binding and Internalization Assay for Adeno-associated Virus.
AB  - The binding and internalization of adeno-associated virus (AAV) is an important
      determinant of viral infectivity and tropism. The ability to dissect these two
      tightly connected cellular processes would allow better understanding and provide
      insight on virus entry and trafficking. In the following protocol, we describe a
      quantitative PCR (qPCR) based method to determine the amount of vector bound to
      the cell surface and the amount of subsequent virus internalization based on
      viral genome quantification. This protocol is optimized for studying AAV.
      Nevertheless, it can serve as a backbone for studying other viruses with careful
      modification.

PMID- 29226180
TI  - Cytosolic and Nuclear Delivery of CRISPR/Cas9-ribonucleoprotein for Gene Editing
      Using Arginine Functionalized Gold Nanoparticles.
AB  - In this protocol, engineered Cas9-ribonucleoprotein (Cas9 protein and sgRNA,
      together called Cas9-RNP) and gold nanoparticles are used to make nanoassemblies
      that are employed to deliver Cas9-RNP into cell cytoplasm and nucleus. Cas9
      protein is engineered with an N-terminus glutamic acid tag (E-tag or En, where n
      = the number of glutamic acid in an E-tag and usually n = 15 or 20), C-terminus
      nuclear localizing signal (NLS), and a C-terminus 6xHis-tag. [Cas9En hereafter]
      To use this protocol, the first step is to generate the required materials (gold
      nanoparticles, recombinant Cas9En, and sgRNA). Laboratory-synthesis of gold
      nanoparticles can take up to a few weeks, but can be synthesized in large batches
      that can be used for many years without compromising the quality. Cas9En can be
      cloned from a regular SpCas9 gene (Addgene plasmid id = 47327), and expressed and
      purified using standard laboratory procedures which are not a part of this
      protocol. Similarly, sgRNA can be laboratory-synthesized using in vitro
      transcription from a template gene (Addgene plasmid id = 51765) or can be
      purchased from various sources. Once these materials are ready, it takes about
      ~30 min to make the Cas9En-RNP complex and 10 min to make the Cas9En
      RNP/nanoparticles nanoassemblies, which are immediately used for delivery (Figure
      1). Complete delivery (90-95% cytoplasmic and nuclear delivery) is achieved in
      less than 3 h. Follow-up editing experiments require additional time based on
      users' need. Synthesis of arginine functionalized gold nanoparticles (ArgNPs)
      (Yang et al., 2011), expression of recombinant Cas9En, and in vitro synthesis of
      sgRNA is reported elsewhere (Mout et al., 2017). We report here only the
      generation of the delivery vehicle i.e., the fabrication of Cas9En-RNP/ArgNPs
      nanoassembly.

PMID- 29226181
TI  - A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate
      Human Cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) infection is a major cause of morbidity and
      mortality in transplant patients and a leading cause of congenital birth defects
      (Saint Louis, 2016). Vaccination and therapeutic studies often require scalable
      cell culture production of wild type virus, represented by clinical isolates.
      Obtaining sufficient stocks of wild-type clinical HCMV is often labor intensive
      and inefficient due to low yield and genetic loss, presenting a barrier to
      studies of clinical isolates. Here we report a bioreactor method based on
      continuous infection, where retinal pigment epithelial (ARPE-19) cells adhered to
      microcarrier beads are infected in a bioreactor and used to produce high-titers
      of clinical isolate HCMV that maintain genetic integrity of key viral tropism
      factors and the viral genome. In this bioreactor, an end-stage infection can be
      maintained by regular addition of uninfected ARPE-19 cells, providing convenient
      preparation of 107-108 pfu/ml of concentrated TB40/E IE2-EYFP stocks without
      daily cell passaging or trypsinization. Overall, this represents a 100-fold
      increase in gain of virus production of 100-times compared to conventional static
      culture plates, while requiring 90% less handling time. Moreover, this continuous
      infection environment has the potential to monitor infection dynamics with
      applications for real-time tracking of viral evolution.

PMID- 29226182
TI  - Assessment of Aversion of Acute Pain Stimulus through Conditioned Place Aversion.
AB  - Pain is a complex experience. The aversive component of pain has been assessed
      through conditioned place aversion in rodents. However, this behavioral test does
      not allow the evaluation of the aversion of an acute pain stimulus. In Zhang et
      al. (2017), we provide an updated version of a Conditioned Place Aversion
      paradigm to address this challenge. In this protocol, a detailed version of this
      method is described.

PMID- 29226183
TI  - In vitro Homeostatic Proliferation of Human CD8 T Cells.
AB  - Long-lived T-cell-mediated immunity requires persistence of memory T cells in an
      antigen-free environment while also maintaining a heightened capacity to recall
      effector functions. Such antigen-independent homeostatic proliferation is
      mediated in part by the common gamma-chain cytokines IL-7 and IL-15. To further
      explore the mechanisms governing maintenance of effector functions in long-lived
      memory T cells during antigen-independent proliferation, human naive and memory
      CD8 T cells can be sorted from peripheral blood mononuclear cells (PBMCs),
      labeled with the proliferation-tracking dye carboxyfluorescein succinimidyl ester
      (CFSE), and then purified based on their levels of cell division. This allows
      investigators to assess differences in the desired molecular target in cells that
      have undergone cytokine-driven proliferation. We provide here a protocol for
      assessing epigenetic programs in divided and undivided human naive and memory CD8
      T cells following 7 days in culture with IL-7 and IL-15 to illustrate how this
      approach can shed light on the mechanism(s) that governs the preservation of
      effector functions during homeostasis of long-lived memory CD8 T cells.

PMID- 29226184
TI  - Cure of Hepatoblastoma Through Transcatheter Arterial Chemoembolization.

PMID- 29226185
TI  - Parental and Pediatricians' Perception of Need for Subspecialty Training in
      Pediatric Emergency Medicine for Delivering Emergency Care to Pediatric Patients.
AB  - The quality of pediatric emergency care may depend on the competence of the
      emergency department physicians. It is important to know whether parents and
      general pediatricians associate the quality of pediatric emergency care with the
      pediatric emergency medicine (PEM) training of the emergency department
      physicians. We designed the study to determine parental and pediatricians'
      opinion and expectation in regard to this question. Most of the surveyed parents'
      and pediatricians' recognize the importance of PEM training and believed that
      physicians trained in PEM can provide better emergency care for children.
      However, 53.8% of parents, especially Spanish speaking and with Medicaid/no
      insurance coverage, believe that the emergency care provided for their children
      by general pediatricians and PEM physicians is equivalent. The results of our
      study could be utilized by accredited PEM planners in the creation of strategies
      to ensure the quality of emergency care for children population.

PMID- 29226186
TI  - Prevalence of Pelvic Incontinence in Patients With Cystic Fibrosis.
AB  - Cystic fibrosis (CF) patients are at risk for developing pelvic (urinary and/or
      fecal) incontinence due to progressive weakness of pelvic floor muscles secondary
      to recurrent episodes of coughing and respiratory infections. Many patients do
      not bring these symptoms to the attention of their health care providers because
      of social embarrassment and lack of knowledge of available effective treatment.
      Several studies have identified the prevalence of incontinence in CF adults and
      adolescents. However, few studies identified the problem in children with CF. Our
      study aims are to identify the prevalence of pelvic incontinence in CF patients
      aged 6 to 21 years, to identify the correlation between incontinence and severity
      of lung disease, and to help develop treatment strategy in collaboration with
      physical therapy to address these issues.

PMID- 29226187
TI  - Tracheobronchial Foreign Bodies in Children: The Role of Emergency Rigid
      Bronchoscopy.
AB  - Foreign body aspiration (FBA) is a common and lethal accident in the pediatric
      age group. It requires early recognition and treatment by rigid bronchoscopy to
      avoid fatal outcomes. Objective. The aim of this study was to study the pattern
      of FBA in the tracheobronchial tree as well as the success rate of rigid
      bronchoscopy in children admitted to a single center and to analyze the
      relationship of the type of foreign body (FB) with patients' age, presentation,
      and complications. Methods. A retrospective cross-sectional study of FBA was
      conducted in children in the Sulaimani/Kurdistan region, Iraq, admitted to the
      emergency teaching hospital of the University of Sulaimani from January 2014 to
      March 2016. Result. Data of 83 patients between 6 months and 15 years old were
      studied. The most affected was the 1- to 5-year-old group. There was a slight
      female predominance (male to female ratio 0.93:1). The most common FB was
      sunflower seed (49.4%). History of choking was present in 92.8% of patients;
      55.4% had normal air entry, and 37.3% had no added sound on chest auscultation.
      Normal chest X-ray (CXR) was found in 40% of patients. The most common site was
      the right bronchial tree (39.8%). Two patients needed mechanical ventilation;
      both of them died. There was a significant relationship between the type of FB (P
      = .013, .000, respectively). Conclusion. Medical history is the most important
      factor for reaching the diagnosis; bronchoscopy is mandatory if choking was
      witnessed, even if examination and CXR are normal. Organic material causes more
      local reaction than nonorganic material.

PMID- 29226188
TI  - Child Abuse Prevention Team Activities in a General Hospital in Tochigi, Japan.

PMID- 29226189
TI  - Night Sweats, Stress Activation and Coeliac Disease.

PMID- 29226190
TI  - Limp in a Child With Autism Spectrum Disorder.

PMID- 29226191
TI  - Time to Drug-Resistant Tuberculosis Treatment in a Prospective South African
      Cohort.
AB  - This study examined time to treatment initiation by age among a prospective
      cohort with drug-resistant tuberculosis (DR-TB). Participants aged 13 years or
      older nested within a cluster-randomized trial in 2 South African provinces were
      evaluated. Outcomes were treatment initiation within 5 days of DR-TB diagnosis
      (National Tuberculosis Program guidelines) and days from diagnosis to treatment.
      A total of 521 participants met inclusion criteria. Eighty-two patients (16%) met
      national guidelines; median time to treatment was 11 days (range = 0-180). No
      patient (age, sex, prior TB history, HIV status) or health system characteristics
      (geographic urban/rural location, province) were associated with treatment
      initiation per guidelines except geographic location (t = 3.64, degrees of
      freedom = 1, P = .0003). One in 6 individuals with DR-TB received treatment per
      guidelines, and average time to treatment was 11 days. Strategies are needed to
      decrease treatment delays and meet the recommended guidelines for treatment for
      patients of all ages.

PMID- 29226192
TI  - Qualitative Assessment of Pregnant Women's Perceptions of Infant Sleep Boxes.
AB  - Although several states have implemented programs providing boxes for infant
      sleep, safe sleep experts express concern regarding the paucity of safety and
      efficacy research on boxes. The purpose of this study was to assess pregnant
      women's perceptions regarding use of baby sleep boxes. A convenience sample was
      recruited from a community prenatal education program. Twenty-eight women were
      administered a brief semistructured interview about their knowledge of baby sleep
      boxes, opinions about the boxes, and questions they would have. For most (n = 15,
      54%), this was their first pregnancy. Participants self-identified as white
      (43%), black (36%), Hispanic (18%), and "other" (4%). Ten subthemes emerged
      related to previous knowledge of boxes (useful for families in need, historic
      precedent in other countries), positive attributes (portable, compact,
      affordable, decorative), and negative attributes (low to ground, structural
      integrity/design, stability, stigma). Research on safety and efficacy could
      reduce concerns, but issues of stigma may persist.

PMID- 29226193
TI  - The Many Presentations of Pneumomediastinum.

PMID- 29226194
TI  - Childhood Socioeconomic Status and Stress in Late Adulthood: A Longitudinal
      Approach to Measuring Allostatic Load.
AB  - Objectives: This study examines how the effects of childhood socioeconomic status
      (SES) may carry on into late adulthood. Methods: We examine how childhood SES
      affects both perceived stress and allostatic load, which is a cumulative measure
      of the body's biologic response to chronic stress. We use the National Social
      Life, Health, and Aging Project, Waves 1 and 2, and suggest a novel method of
      incorporating a longitudinal allostatic load measure. Results: Individuals who
      grew up in low SES households have higher allostatic load scores in late
      adulthood, and this association is mediated mostly by educational attainment.
      Discussion: The longitudinal allostatic load measure shows similar results to the
      singular measures and allows us to include 2 time points into one outcome
      measure. Incorporating 2 separate time points into one measure is important
      because allostatic load is a measure of cumulative physiological dysregulation,
      and longitudinal data provide a more comprehensive measure.

PMID- 29226195
TI  - Consequences of Inconsistency in Air Force Tobacco Control Policy.
AB  - Objectives: Although the United States Air Force (USAF) has been a leader in
      efforts to reduce tobacco use among service members, tobacco continues to be a
      problem and initiatives to decrease tobacco use further require buy-in from
      leadership. We explored line leaderships' perspectives on tobacco. Methods: A
      diverse group of 10 senior commissioned and 10 non-commissioned personnel were
      interviewed. Results: Respondents reported substantial changes in the culture of
      tobacco use during their years of service, from near ubiquity to restricted use
      areas. They also perceived mixed messages coming from the USAF, including
      simultaneous discouragement of and accommodations for tobacco use, and
      variability in policies and enforcement. Many respondents indicated that allowing
      tobacco use creates conflict and undermines military discipline and suggested
      that a tobacco-free policy would be the best way to eliminate these
      contradictions. Conclusion: Although there has been substantial movement away
      from a culture of tobacco in the USAF, current policies and variable enforcement
      of these policies create unnecessary contradictions. Establishing a tobacco-free
      service would resolve these issues in addition to improving the health of service
      members and veterans.

PMID- 29226196
TI  - Orthopedic History in Iran: Ancient, Contemporary and Modern Times.

PMID- 29226198
TI  - Restoration of the Mechanical Axis in Total Knee Artrhoplasty Using Patient
      Matched Technology Cutting Blocks. A Retrospective Study of 132 Cases.
AB  - Background: The aim of this study is to evaluate the accuracy of bone cuts and
      the resultant alignment, using the MyKnee patient specific cutting blocks.
      Methods: We retrospectively reviewed 132 patients undergoing primary TKR for
      osteoarthritis by one single surgeon. The operative time, the preoperative Hip
      Knee-Ankle (HKA) axis based on the CT-scan, the postoperative HKA axis based on
      long axis standing x-rays, the planned and the actual size of the femoral and the
      tibial components, and the number of the recuts which has been made
      intraoperative were measured. Results: The average preoperative HKA axis was
      177.50 (range 163.50 to 1940), whereas the average postoperative HKA axis was
      179.40 (range 177.10 to 182.70). No outliers were reported in the study (0%).
      Intraoperatively, 4 femoral components (3.03%), and 7 tibial components (5.30%)
      applied to the patients were different than the planned size. There was no need
      of recuts in any of our cases intraoperatively. Conclusion: The MyKnee system
      evaluated in this study was shown to be remarkable reliable in the coronal plane
      alignment, and the prediction of the component size. However, further studies are
      needed to determine whether there are any clinically important improvements in
      outcomes or patient satisfaction when using patient-specific cutting blocks for
      TKA.

PMID- 29226197
TI  - Osteoporosis and the Management of Spinal Degenerative Disease (I).
AB  - Osteoporosis has become a major medical problem as the aged population of the
      world rapidly grows. Osteoporosis predisposes patients to fracture, progressive
      spinal deformities, and stenosis, and is subject to be a major concern before
      performing spine surgery, especially with bone fusions and instrumentation.
      Osteoporosis has often been considered a contraindication for spinal surgery,
      while in some instances patients have undergone limited and inadequate procedures
      in order to avoid concomitant instrumentation. As the population ages and the
      expectations of older patients increase, the demand for surgical treatment in
      older patients with osteoporosis and spinal degenerative diseases becomes
      progressively more important. Nowadays, advances in surgical and anesthetic
      technology make it possible to operate successfully on elderly patients who no
      longer accept disabling physical conditions. This article discusses the
      biomechanics of the osteoporotic spine, the diagnosis and management of
      osteoporotic patients with spinal conditions, as well as the novel treatments,
      recommendations, surgical indications, strategies and instrumentation in patients
      with osteoporosis who need spine operations.

PMID- 29226199
TI  - Effectiveness of Minimally Invasive Plate Osteosynthesis (MIPO) on Comminuted
      Tibial or Femoral Fractures.
AB  - Background: Comminuted fractures happen frequently due to traumas. Fixation
      without opening the fracture site, known as minimally invasive plate
      osteosynthesis (MIPO), has recently become prevalent. This study has been
      designed to assess the outcomes of this treatment for tibial and femoral
      comminuted fractures. Methods: A total of 60 patients with comminuted femoral or
      tibial fractures were operated with MIPO method in this cross-sectional study at
      Alzahra university hospital in 2015. Eleven patients were excluded due to lack of
      adequate follow-ups. Patients'data including union time; infection in the
      fractured site; hip and knee range of motion; and any malunion or deformities
      like limb length discrepancy were collected after the surgery in every session.
      Results: Among 32 femoral and 17 tibial fractures, union was completed in48
      patients, while only one patient with femoral fracture had nonunion. The mean
      union time was 18.57+/-2.42 weeks. Femur fractures healed faster than tibia
      (17.76+/-2.36 compared to 19+/-2.37 weeks, respectively, P=0.09). None of the
      patients suffered from infections or fistula. The range of motion in hip and knee
      remained intact in approximately all patients. Malunion happened in 3 patients;
      100 internal rotation in 1 patient; and 1cm limb shortening in 2 patients.
      Conclusion: According to the result of this study, MIPO is a simple and effective
      method of fixation with a high rate of union as well as minimal complications for
      comminuted fractures of long bones. Infection is rare, and malunion or any
      deformity is infrequent. MIPO appears to be a promising and safe treatment
      alternative for comminuted fractures.

PMID- 29226200
TI  - Long-term Results of Osteoarticular Allograft Reconstruction in Children with
      Distal Femoral Bone Tumors.
AB  - Background: There is no consensus regarding the best method of reconstruction in
      pediatric population following the wide resection of malignant bone tumors. More
      exploration of the complications of osteoarticular reconstruction leads to less
      existing controversy of this type of reconstruction, which is the main point of
      this article. Methods: Long-term outcomes and complications of osteoarticular
      allograft reconstruction of primary distal femoral bone sarcomas in 22 children
      with mean age of 10.7 years old were reviewed in this study. Musculoskeletal
      Tumor Society (MSTS) scoring system was used for functional evaluation of the
      allografts. Results: With an average follow-up time of 81 months, the outcomes of
      16 patients with allografts at the final follow up were evaluated. As expected,
      Limb length discrepancy (LLD) was observed in all patients (mean LLD= 2.73cm),
      which was significantly correlated to allograft survival time (P<0.001).
      Degenerative joint disease (DJD) was also seen in all patients and its grade was
      also significantly correlated to allograft survival time (P<0.001). The mean MSTS
      score was 74% at the latest follow-up, ranging from 60% to 90%. Five and 10 year
      survival rate of allografts were found to be 93.3% and 62.2%, respectively.
      Conclusion: Osteoarticular allograft reconstruction could result in several
      complications including DJD. Despite its considerable biologic advantage over
      endoprosthesis, osteoarticular allograft reconstruction is a long-lasting but
      still a temporary solution before performing megaprosthesis. This allows patients
      to preserve their remaining physis for limb growth and become old enough for an
      adult megaprosthesis.

PMID- 29226201
TI  - Acute Primary Total Knee Arthroplasty for Proximal Tibial Fractures in Elderly.
AB  - Background: Proximal tibial fractures in elderly patients with osteoporosis or
      knee osteoarthritis (OA) are challenging cases. In the current study, we present
      our experience with uncommon acute primary total knee arthroplasty (PTKA) in this
      patient population. Methods: PTKAs were performed following proximal tibial
      fractures in 30 consecutive patients over 60 years of age with osteoporosis or
      knee OA between 2005 and 2009. Three constrained condylar knees (CCK) and no
      hinged knee prosthesis were used. Patients were followed up for 4.5+/-1.1 years.
      Results: Patients were discharged after 4.6+/-1.2 days. The postoperative Tegner
      activity scale (3.5+/-1.3) was improved significantly compared to the
      preoperative scale (2.5+/-1.2) (P<0.001). The knee flexion range was
      significantly greater in the operated side (106+/-13 degrees) compared to the
      uninjured knee (120+/-8 degrees) (P<0.001). The two sections of knee society knee
      score (knee and function section) averaged 90.7+/-6.5 and 69.6+/-8.8,
      respectively. All patients returned to their previous activities. Based on the
      visual analogue scale, the patients' satisfaction and pain at final visit were
      scored 8.1+/-1 and 1.5+/-1.2, respectively. No infection, thromboembolic events
      and loosening were observed. Conclusion: PTKA following a proximal tibial
      fracture in elderly patients with osteoporosis or knee degeneration can be
      considered as a safe alternative for open reduction and internal fixation. PTKA
      resulted in immediate weight-bearing, improved functional status and patients'
      satisfaction. However, functional outcomes were dependent on the general
      condition of 24 the patient. Also, constrained knee prostheses were not necessary
      for a vast majority of the patients.

PMID- 29226202
TI  - Interobserver Variability of Radiographic Assessment Using a Mobile Messaging
      Application as a Teleconsultation Tool.
AB  - Background: To examine whether interobserver reliability, decision-making, and
      confidence in decision-making in the treatment of distal radius fractures changes
      if radiographs are viewed on a messenger application on a mobile phone compared
      to a standard DICOM viewer. Methods: Radiographs of distal radius fractures were
      presented to surgeons on either a smart phone using a mobile messenger
      application or a laptop using a DICOM viewer application. Twenty observers
      participated: 10 (50%) were randomly assigned to the DICOM viewer group and 10
      (50%) to the mobile messenger group. Each observer was asked to evaluate the
      cases and (1) classify the fracture type according to the AO classification, (2)
      recommend operative or conservative treatment and (3) rate their confidence about
      this decision. Results: There was no significant difference in interobserver
      reliability for AO classification and recommendation for surgery for distal
      radius fractures in both groups. The percentage of recommendation for surgery was
      significantly higher in the messenger application group compared to the DICOM
      viewer group (89% versus 78%, P=0.019) and the confidence for treatment decision
      was significantly higher in the mobile messenger group compared to the DICOM
      viewer group (8.9 versus 7.9, P=0.026). Conclusion: Messenger applications on
      mobile phones could facilitate remote decision-making for patients with distal
      radius fractures, but should be used with caution.

PMID- 29226203
TI  - Blood Glucose Levels in Diabetic Patients Following Corticosteroid Injections
      into the Subacromial Space of the Shoulder.
AB  - Background: Corticosteroid injections are used to treat a variety of orthopedic
      conditions with the goal of decreasing pain and inflammation. Administration of
      systemic or local corticosteroids risks temporarily increasing blood glucose
      levels, especially diabetic patients. The purpose of this study is to quantify
      the effects of corticosteroid injections on blood glucose levels in diabetic
      patients with shoulder pathology. Methods: Diabetic patients who regularly
      monitored their blood glucose levels and were indicated for a subacromial
      corticosteroid injection were included in this prospective investigation. The
      typical normal morning fasting glucose and most recent hemoglobin A1c level was
      recorded for each patient. After injection, patients were contacted daily to
      confirm their fasting morning glucose level for 10 days post-injection. Results:
      Seventeen consecutive patients were enrolled. Patients with hemoglobin A1c of <7%
      had an average rise in blood glucose of 38 mg/dL compared to 98 mg/dL in the
      poorly controlled group after injection (P<0.001). Well-controlled patients'
      glucose levels returned to near baseline levels around post-injection day 8,
      while poorly controlled patients levels remained elevated. Similarly, insulin
      dependent diabetic patients had an average increase in fasting glucose level of
      99 mg/dL versus 50 mg/dL in non-insulin-dependent diabetic patients (P<0.001).
      Conclusion: After corticosteroid injection, patients with well-controlled
      diabetes experience smaller elevations and faster return to baseline glucose
      levels than patients with poor control. Insulin dependent diabetics experienced
      similar findings as patients with poor control. Future studies are needed to
      evaluate dosing to optimize the risks of blood glucose elevation while
      maintaining therapeutic benefit.

PMID- 29226204
TI  - Single Cut Distal Femoral Varus Osteotomy (SCFO): A Preliminary Study.
AB  - Background: Genu valgum usually originates from a deformity of distal femur that
      is often corrected by distal femoral varus osteotomy. The osteotomy includes both
      components of angulationcorrection and translation because the site of osteotomy
      is not commonly at the apex of deformity. Improvement of patellar tracking not
      only depends on valgus correction, but also it may be partially due to
      centralization of the trochlear groove under the femoral anatomical axis (FAA).We
      asked whether we could accurately correct the deformities based on our
      preoperative goals for the correction of the mechanical axis and centralization
      of the trochlear groove under the FAA by using a single bone cut.This study
      describes a new lateral single cut distal femoral osteotomy (SCFO) that enables
      concurrent correction of angulation and translation. Methods: This study was done
      on 12 young adult patients with femoral juxta-articular genu valgum deformity
      using SCFO. The average age at operation was 21 years (range: 16-25). SCFO is a
      type of closing-opening distal femoral osteotomy that corrects the valgus
      deformity of the distal femur while the translation of the distal fragment is
      done using one oblique cut. It centralizes the trochlear groove under the FAA. We
      compared the pre and postoperative radiographic and clinical variables including
      mechanical tibiofemoral angle, knee range of motion (ROM), International knee
      documentation committee (IKDC) score and the time to union. Mean follow-up of the
      patients was 24 months. Results: The average mechanical tibiofemoral angle
      improved from 16 degrees (10-23) to 1 degrees (-2 to +2). IKDC subjective score
      slightly improved from preoperative (65) to 2-year follow-up (71). Centralization
      of the trochlea was achieved in all patients. Conclusion: SCFO can be a
      reasonable alternative for correction of the distal femur genu valgum deformity.
      It can centralize the patellar groove under the FAA with satisfactory clinical
      outcomes.

PMID- 29226205
TI  - Clinical Results of Platelet-Rich Plasma for Partial Thickness Rotator Cuff
      Tears: A Case Series.
AB  - Partial thickness rotator cuff tears (PTRCTs) are a common pathology among
      shoulder disorders in people over 50 years. Treatment of PTRCTs remains
      controversial. Most studies on the treatment of PTRCTs have explained surgical
      techniques or outcomes; few studies have centralized on the conservative and new
      management of PTRCTs, like treatment with Platelet-rich plasma (PRP). These case
      series study have been conducted on Platelet-rich plasma (PRP) injection, as a
      concentrated source of cytokines that can stimulate healing of soft tissue. PRP
      injection showed positive effect on improving PTRCTs complains. This method
      improved pain, function, DASH score and shoulder joint range motion in. Because
      of PRP products are safe and easy to prepare and apply, and also according to
      improving patient's condition, this method can be used to treat PTRCTs.

PMID- 29226206
TI  - Unusual Complete Isolated Scaphoid Dislocation, Report of a Case.
AB  - Isolated scaphoid dislocations are extremely rare injuries and are commonly
      associated with significant ligamentous disruptions. A dorsiflexion-supination
      force upon the hand is considered as the most common mechanism of injury.
      Different treatment options have been proposed for the management of this
      uncommon entity, ranging from conservative treatment with closed reduction and
      casting to a wide range of open or percutaneous surgical techniques. In this
      article, we reported ona case of this rare injury managed with open reduction and
      pinning along with ligamentous reconstruction.

PMID- 29226207
TI  - Open Anterior Hip Dislocation in A Child: A Rare Mechanism of Injury.
AB  - Traumatic anterior dislocation of the hip is an extremely rare condition in
      children and open dislocation is even rarer. This isusually caused by high-energy
      trauma. In the current study, we present a case of an eight-year-old child
      suffering from an open anterior-inferior dislocation of the right hip concomitant
      with pelvic ring disruption and an ipsilateral open distal femoral fracture
      (Salter-Harris type 4, Gustilo type IIIA) caused by a traffic accident. The
      patient underwent successful emergent open reduction due to the buttonholed
      femoral head after appropriate irrigation and debridement. Successful recovery
      was achieved and the patient was discharged after two weeks. After nine months of
      follow-up, the X-ray images showed slight changes related to the osteonecrosis of
      the femoral head. Long-term follow-up over a period of six years showed
      sufficient range of motion. The patient's gait was normal and he was satisfied
      with the outcome. In addition, slight non-progressive osteonecrotic changes were
      obvious in the right hip.

PMID- 29226208
TI  - Brucella Arthritis Following Total Knee Arthroplasty in a Patient with
      Hemophilia: A Case Report.
AB  - Total knee arthroplasty (TKA) is a rewarding procedure in patients with
      hemophilia and end stage knee hemophilic arthropathy. However, this procedure
      might be associated with complications such as infection. There periprosthetic
      joint infection in patients with hemophilia is very well known, though we are not
      aware of any previous report on Brucella infection in this group of patients.
      Here, we reported a 28-year old man with Brucella infection of total knee
      replacement who initially underwent a conservative treatment followed bya two
      stage revision. We believe that this report will alert physicians who work in
      endemic area for brucellosis to consider this in differential diagnosis and do
      the right intervention at the right time.

PMID- 29226209
TI  - A reconstructed database of historic bluefin tuna captures in the Gibraltar
      Strait and Western Mediterranean.
AB  - This data paper presents a reconstruction of a compilation of a small but
      consistent database of historical capture records of bluefin tuna (Thunnus
      thynnus; BFT hereafter) from the Gibraltar Strait and Western Mediterranean
      (Portugal, Spain and Italy). The compilation come from diverse historical and
      documentary sources and span the time interval from 1525 to 1936 covering a
      period of 412 years. There is a total of 3074 datum, which reach up to 67.83% of
      the total implying a 32.17% of missing data. However, we have only reconstructed
      the captures for the time interval 1700-1936 and we provide these reconstructions
      only for this time interval and for 9 out of 11 series due to the scarcity and
      inhomogeneity of the two oldest capture time series. This reconstructed database
      provides an invaluable opportunity for fisheries and marine research as well as
      for multidisciplinary research in climate change.

PMID- 29226210
TI  - Data and analyses of phase relations in the Ce-Fe-Sb ternary system.
AB  - These data and analyses support the research article "Experimental study on phase
      relations in the Ce-Fe-Sb ternary system" Zhu et al. (2017) [1]. The data and
      analyses presented here include the experimental results of XRD, SEM and EPMA for
      the determination of the whole liquidus projection and the isothermal section at
      823 K in the Ce-Fe-Sb system. All the results enable the understanding of the
      constituent phases and the solidification processes of the as-cast alloys as well
      as the phase relations and the equilibrium regions at 823 K in the Ce-Fe-Sb
      ternary system over the entire composition.

PMID- 29226211
TI  - An 18-subject EEG data collection using a visual-oddball task, designed for
      benchmarking algorithms and headset performance comparisons.
AB  - This data note describes an 18-subject EEG (electroencephalogram) data collection
      from an experiment in which subjects performed a standard visual oddball task.
      Several research projects have used this data to test artifact detection,
      classification, transfer learning, EEG preprocessing, blink detection, and
      automated annotation algorithms. We are releasing the data in three formats to
      enable benchmarking of EEG algorithms in many areas. The data was acquired using
      a Biosemi Active 2 EEG headset and includes 64 channels of EEG, 4 channels of EOG
      (electrooculogram), and 2 mastoid reference channels.

PMID- 29226212
TI  - Data on fatty acid profiles of green Spanish-style Gordal table olives studied by
      compositional analysis.
AB  - This article contains processed data related to the research published in
      "Tentative application of compositional data analysis to fatty acid profiles of
      green Spanish-style Gordal table olives" (Garrido-Fernandez et al., 2018) [1]. It
      provides information on the implementation of compositional data analysis (CoDa)
      to the fatty acid profiles of Spanish-style Gordal table olives vs the use of
      conventional statistical analysis (data composition expressed in percentages).
      Particularly, it includes: i) the matrix of the sequential binary partition used
      for the balance estimation and the isometric log-ratio transformation (ilr) of
      the fatty acid profiles, ii) correlation among the diverse fatty acids expressed
      in percentages and their significances, iii) the ilr transformed values
      (coordinates in the Euclidean space) obtained following the sequential binary
      partition previously detailed, iv) the graphical presentation in the Simplex
      (ternary centred plot) of the treatments as a function of the four fatty acids
      with the higher log-ratio variances, and v) segregation of treatments based on
      Cluster Analysis.

PMID- 29226213
TI  - Reference ranges and reproducibility studies for right heart myocardial
      deformation by feature tracking cardiovascular magnetic resonance imaging.
AB  - Feature tracking of the right heart on cardiac MRI is a novel and promising
      technique for the measurement of right heart myocardial strain. We present here
      the reference ranges for right ventricular longitudinal strain and strain rate,
      as well as peak strain of the right atrium within a cohort of 100 healthy
      individuals recruited from the UK. We present data on the reproducibility of
      these feature tracking techniques and explore relationship between strain and
      baseline demographic parameters.

PMID- 29226214
TI  - The legacy of slavery and contemporary declines in heart disease mortality in the
      U.S. South.
AB  - Background: This study aims to characterize the role of county-specific legacy of
      slavery in patterning temporal (i.e., 1968-2014), and geographic (i.e., Southern
      counties) declines in heart disease mortality. In this context, the U.S. has
      witnessed dramatic declines in heart disease mortality since the 1960's, which
      have benefitted place and race groups unevenly, with slower declines in the
      South, especially for the Black population. Methods: Age-adjusted race- and
      county-specific mortality rates from 1968-2014 for all diseases of the heart were
      calculated for all Southern U.S. counties. Candidate confounding and mediating
      covariates from 1860, 1930, and 1970, were combined with mortality data in
      multivariable regression models to estimate the ecological association between
      the concentration of slavery in1860 and declines in heart disease mortality from
      1968-2014. Results: Black populations, in counties with a history of highest
      versus lowest concentration of slavery, experienced a 17% slower decline in heart
      disease mortality. The association for Black populations varied by region
      (stronger in Deep South than Upper South states) and was partially explained by
      intervening socioeconomic factors. In models accounting for spatial
      autocorrelation, there was no association between slave concentration and heart
      disease mortality decline for Whites. Conclusions: Nearly 50 years of declining
      heart disease mortality is a major public health success, but one marked by
      uneven progress by place and race. At the county level, progress in heart disease
      mortality reduction among Blacks is associated with place-based historical legacy
      of slavery. Effective and equitable public health prevention efforts should
      consider the historical context of place and the social and economic institutions
      that may play a role in facilitating or impeding diffusion of prevention efforts
      thereby producing heart healthy places and populations. Graphical abstract.

PMID- 29226215
TI  - In Vitro Antifungal Activity of Hexahydropyrimidine Derivatives against the
      Causative Agents of Dermatomycosis.
AB  - Nitrogenated heterocyclic compounds are present in both natural and synthetic
      drugs, and hexahydropyrimidine derivatives may prove to be efficient in treating
      dermatomycosis causing fungi. This study evaluated the antifungal activity of
      four hexahydropyrimidine derivatives against the dermatomycosis causing fungi.
      These derivatives were synthesized, characterized, and assessed in terms of their
      activity against Trichophyton mentagrophytes, Microsporum canis, Microsporum
      gypseum, Trichophyton rubrum, Fusarium oxysporum, and Epidermophyton floccosum
      between concentrations 7.8 and 1,000 MUg mL-1. Scanning electron micrographs were
      assessed for the active derivatives and reference drugs, and these micrographs
      revealed that new agents cause morphological changes in fungi. The derivatives
      HHP1, HHP3, and HHP4 revealed poor activity against the four fungal strains (MICs
      range 500-1000 MUg mL-1). Compound HHP3 was found to be the best potential
      antifungal agent among those tested and was the most effective among all the
      active derivatives that caused morphological changes in the susceptible strains.

PMID- 29226216
TI  - Prevalence and Associated Factors of Tuberculosis in Prisons Settings of East
      Gojjam Zone, Northwest Ethiopia.
AB  - Background: Tuberculosis, mainly in prisoners, is a major public health problem
      in Ethiopia where there is no medical screening during prison admission. This
      creates scarcity of TB data in such settings. Objective: To determine prevalence
      and associated factors of TB in prisons in East Gojjam Zone, Northwest Ethiopia.
      Methods: A cross-sectional study was conducted from February to May 2016 among
      265 prisoners in three prison sites. Sputum was processed using GeneXpert
      MTB/RIF. Data were analyzed using SPSS version 20.0. Multivariable logistic
      regression was used; p values = 0.05 were considered statistically significant.
      Results: Of 265 prisoners, 9 (3.4%) were TB positive (males); 77.8%, 55.6%, and
      55.6% of cases were rural dwellers, married, and farmers, respectively. Seven
      (2.6%) prisoners were HIV positive, and 3 (1.13%) had TB/HIV coinfection. One
      (0.4%) TB case was rifampicin resistant. Marriage (AOR = 1.5; 95% CI: 1.7,
      13.03), HIV (AOR = 0.14; 95% CI: 0.001, 0.17), and sharing of rooms (AOR = 1.62;
      95% CI: 2.6, 10.20) were predictors for TB. Conclusion: Nine prisoners were TB
      positive. One case showed rifampicin resistance and three had TB/HIV coinfection.
      Marriage, HIV, and sharing of rooms were predictors for TB. Prevention/control
      and monitoring are mandatory in such settings.

PMID- 29226217
TI  - Lipid Profile in Tuberculosis Patients with and without Human Immunodeficiency
      Virus Infection.
AB  - Background: Understanding whether the preceding low lipid profile leads to active
      tuberculosis (TB) or active TB leads to low lipid profile is crucial. Methods:
      Lipid profile concentrations were determined from 159 study participants composed
      of 93 active TB patients [44 HIV coinfected (HIV+TB+) and 49 HIV negative (HIV
      TB+)], 41 tuberculin skin test (TST) positive cases [17 HIV coinfected (HIV+TST+)
      and 24 HIV negative (HIV-TST+)], and 25 healthy controls (HIV-TST-). Cobas
      Integra 400 Plus was used to determine lipid profiles concentration level.
      Results: The concentrations of total cholesterol (TC), triglyceride (TG), low
      density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol
      (HDL-C) in HIV-TB+ patients were significantly lower compared to HIV-TST+ and to
      HIV-TST- individuals. Similarly, the concentrations of the TC, LDL-C, and HDL-C
      in HIV+TB+ were significantly lower compared to HIV-TB+ patients. After the 6
      months of anti-TB treatment (ATT), the concentration levels of TC, LDL-C, and HDL
      C in HIV-TB+ patients were higher compared to the baseline concentration levels,
      while they were not significantly different compared to that of HIV-TST+
      concentration. Conclusion: The low concentration of lipid profiles in TB patients
      may be a consequence of the disease and significantly increased in TB patients
      after treatment.

PMID- 29226218
TI  - Clinical effectiveness of the pocket-creation method for colorectal endoscopic
      submucosal dissection.
AB  - Background and study aims : Endoscopic submucosal dissection (ESD) is a
      technically advanced procedure for colorectal tumors. Hayashi et al. invented the
      "pocket-creation method (PCM)," and reported that Is-type lesions with fibrosis
      could be efficaciously and safely resected. However, only case studies have been
      published, and there are no previous reports on the usefulness of PCM in
      colorectal ESD for all lesions, as compared with the conventional method. This
      study aimed to evaluate the effectiveness and safety of PCM in colorectal ESD.
      Patients and methods : Ninety-six colorectal tumors were treated: 47 using the
      PCM and the other 49, considered the control group, using the conventional
      method. Therapeutic effectiveness and safety were retrospectively assessed.
      Results : The comparison between the PCM and control groups revealed higher rates
      of en bloc resection (100 % vs. 88 %, P  = 0.015) and curative endoscopic
      resection (100 % vs. 84 %, P  = 0.0030) with PCM. There was no significant
      difference in perforation as an adverse event (AE) between the two groups, though
      perforation was observed in only 6 % of the control group and none of the PCM
      group. Compared with the control group, the PCM group had lower incidences of
      perforation and post-ESD coagulation syndrome, and both AEs were associated with
      excessive thermal denaturation of the muscle layer (2 % vs. 16 %, P  = 0.018).
      Conclusions : This study demonstrated the effectiveness and safety of ESD with
      PCM for colorectal tumors. Although there is a possible learning curve, PCM
      enables the endoscopist to safely perform ESD in most cases without encountering
      the difficulties associated with conventional ESD.

PMID- 29226219
TI  - Systematic optimization and modification of a DNA aptamer with 2'-O-methyl RNA
      analogues.
AB  - Nucleic acid aptamers (NAAs) are short synthetic DNA or RNA molecules that
      specifically fold into distinct three-dimensional structures able to specifically
      recognize a target. While NAAs show unprecedented promise in a variety of
      applications, including sensing, therapeutics and diagnostics, one major
      limitation involves the lack of stability towards omnipresent nucleases.
      Therefore, we herein report a systematic truncation and incorporation of 2'-O
      methyl bases to a DNA aptamer, which results in increased stability without
      affecting affinity. One of the newly designed analogues is stable up to 24 hours,
      demonstrating that 2'-O-methyl RNA is an attractive modification to DNA aptamers,
      especially when therapeutic applications are intended.

PMID- 29226220
TI  - Initial Results of the Master's Degree Programme in "Leadership in Medicine" -
      Impact on hospital-based follow-on training of doctors.
AB  - Objective: This pilot project, which was jointly conducted by a hospital and a
      university, describes the development of the Master's Degree Programme in
      Leadership in Medicine, a course designed to supplement medical specialty
      training. The aim of the pilot project is to demonstrate how hospital-based
      projects on personnel and organisational development undertaken under academic
      supervision can be used to increase leadership responsibility among doctors whose
      duties include providing initial and follow-on training and to professionalise
      medical specialty training as a leadership task. This need arose from the
      nationwide requirements and an internal audit regarding follow-on training. The
      version of the degree programme described below aims to further the personnel
      development of the participants in the field of didactics. Method: Each of the
      nine modules is made up of two classroom-based phases and one distance learning
      phase. The distance learning phase involves undertaking hospital-based projects
      on personnel and organisational development under academic supervision. The pilot
      phase participants were hospital doctors who, as part of their duties, hold
      leadership responsibility or are involved in the follow-on training of doctors.
      Results: The 17 participants successfully implemented more than 30 hospital-based
      projects during the distance learning phases of the nine modules. These projects
      included the development of medical specialty curricula, relevant didactic
      methods and evaluation design and were subsequently presented and subjected to
      reflection in interdisciplinary groups. The project presentation together with
      the project report were regarded as proof of competency. Conclusion: In addition
      to enhancing participant competency, the degree model described, which interlinks
      theory and practice, promotes organisational development through the
      implementation of projects undertaken under academic supervision. This has a
      double impact on the quality of medical follow-on training at the hospital where
      the participant is based, for not only is the individual's didactic competency
      enhanced, but so is the "learning organisation" as a whole as a result of
      continuous project orientation.

PMID- 29226221
TI  - Male and female residents in postgraduate medical education - A gender
      comparative analysis of differences in career perspectives and their conditions
      in Germany.
AB  - Aim: This article focuses on the gender-specific career differences of residents
      in their postgraduate medical education in Germany. In particular the structural
      obstacles female physicians have to overcome during residency are investigated.
      Moreover, the study examines the position preferences of male and female
      physicians in the hospital and in how far occupational self-efficacy corresponds
      to the interest in a hospital leading position. Methods: The KarMed-Study's
      database consists of annual postal surveys throughout the entire residency of
      medical students, who were in their "Practical Year" in 2008/2009. Descriptive
      statistics and regression models were used in the analysis. Results: Male and
      female physicians differ in terms of their preferred work place (hospital,
      ambulatory care, others), hospital position and working hours. Female physicians
      prefer part-time work and rarely assume leading positions compared to male
      physicians. In addition, female physicians, especially those with children, need
      more time to complete their postgraduate training. Female physicians with
      children are burdened and disadvantaged more often than their female colleagues
      without children as well as male physicians in general (e.g. belated start and
      completion of residency, lower rate of doctorate titles, higher quota of part
      time contracts, short-term employment contracts, and higher rates of residency
      interruption or termination). Besides gender and doctorate title, the
      occupational self-efficacy expectation has an influence on the preference of
      leading positions in hospitals. Respondents with a low occupational self-efficacy
      score are less likely to strive for leading positions with more responsibilities
      than those with a high score. Conclusion: The results demonstrate clear gender
      disparities in postgraduate training. Female physicians, especially those with
      children, are disadvantaged in various areas when compared with their male
      colleagues. In particular, the low rate of doctorate titles and the low score of
      self-efficacy expectation are associated negatively with the willingness to aim
      at leading positions in hospitals. Special measures and programmes should be
      developed for female physicians to counteract these differences.

PMID- 29226222
TI  - Learning processes and learning problems in German postgraduate medical
      education.
AB  - Objective: In order to evaluate the quality of postgraduate medical education in
      Germany, we examined how the learning of theoretical and practical competencies
      is conceptualized and how the learning process takes place in real terms. The
      training conditions, as perceived by medical residents, are compared with the
      learning objectives, as stated by the Federal Chamber of Physicians in its
      regulation on postgraduate education. The analysis is based on the data of the
      "KarMed" study (abbreviation of "career progression and career breaks among
      physicians during postgraduate education"), a multicentre cohort study of medical
      school graduates from seven universities who arre followed until they receive
      their licenses as specialist physicians. The study was conducted by the Institute
      of Primary Medical Care of the University Medical Center Hamburg-Eppendorf
      starting in 2008. Methodology: The KarMed study is based on annual, standardized
      surveys of the population described above. 48% responded in the initial survey
      (n=1012) and 85% or more in each of the following surveys. Descriptive statistics
      and logistical regressions were used for analysis. Gender-specific analyses were
      performed where possible in order to highlight the differences in the
      professional objectives and workloads between female and male physicians.
      Results: The study shows that both the practical and the theoretical components
      of postgraduate medical education in Germany are insufficient. There is a lack of
      a curriculum with precise learning objectives and descriptions of the
      corresponding educational settings. In fact, the act of learning is identical to
      daily clinical work. There is no structuring of the work process with regard to
      learning; for example, documentation procedures and feedback discussions are
      prescribed but largely omitted. Evidence-based medicine is not a systematic part
      of the training, nor is the evaluation of residents' progress. The summative
      final oral examination pretends that the necessary specialist competencies can be
      evaluated within 30 minutes. Many factors indicate that female doctors,
      especially those with children, have fewer learning opportunities than male
      doctors. Conclusion: The quality of postgraduate medical education in Germany has
      become inadequate, especially in an international comparison. The deficits are
      well known. The responsible institutions are called upon to implement sustainable
      reforms in the sense of postgraduate education that is structured according to
      educational principles and whose quality is assured.

PMID- 29226223
TI  - Three years of experience with a workshop for medical specialty examiners in
      South Baden: A project report and initial evaluation results.
AB  - Introduction: An oral exam (30-60 minutes) is administered at the end of every
      post-graduate medical specialty program or is required to attain additional
      specialized qualifications. In both undergraduate and post-graduate medical
      education oral exams are not considered to be very objective or reliable. To
      improve the quality of exams in medical specialties, the Regional Medical
      Association for South Baden (Bezirksarztekammer Sudbaden) decided in 2013 to
      offer a training program for head examiners and others responsible for
      administering exams in medical specialties. Project Description: Following a
      survey of examiners and examinees conducted from January through June, 2013, on
      the difficulty level of examination questions, satisfaction with the test, and
      the need for training in administering exams, the first workshop of its kind was
      designed. Since 2013, six workshops with a total of 93 participants have been
      held and evaluated. Results: The evaluations (response rate: 86%) showed a high
      level of acceptance for the concept behind the training. A large number of
      participants felt the need to define minimum standards for exams, to standardize
      the required level of difficulty and the assessment criteria in each subject, and
      to give examiners the appropriate tools needed to improve the validity and
      reliability of the exams. Conclusion: Offering a training program for those
      responsible for administering medical specialty exams appears to be both
      meaningful and necessary in order to meet the existing need for increased
      validity and reliability. In light of the initial experiences with this workshop
      and the differing percentages of failed exam attempts nationwide, the
      implementation of examiner training is to be recommended in other regions in
      Germany. In other European countries examiners conducting medical specialty exams
      undergo appropriate training before administering their first exam.

PMID- 29226224
TI  - An application of programmatic assessment for learning (PAL) system for general
      practice training.
AB  - Aim: Programmatic assessment for learning (PAL) is becoming more and more popular
      as a concept but its implementation is not without problems. In this paper we
      describe the design principles behind a PAL program in a general practice
      training context. Design principles: The PAL program was designed to optimise the
      meaningfulness of assessment information for the registrar and to make him/her
      use that information to self regulate their learning. The main principles in the
      program were cognitivist and transformative. The main cognitive principles we
      used were fostering the understanding of deep structures and stimulating transfer
      by making registrars constantly connect practice experiences with background
      knowledge. Ericsson's deliberate practice approach was built in with regard to
      the provision of feedback combined with Pintrich's model of self regulation.
      Mezirow's transformative learning and insights from social network theory on
      collaborative learning were used to support the registrars in their development
      to become GP professionals. Finally the principal of test enhanced learning was
      optimised. Epilogue: We have provided this example explain the design decisions
      behind our program, but not want to present our program as the solution to any
      given situation.

PMID- 29226225
TI  - The use of a portfolio in postgraduate medical education - reflect, assess and
      account, one for each or all in one?
AB  - Competency-based education has become central to the training and assessment of
      post-graduate medical trainees or residents [1]. In competency-based education,
      there is a strong focus on outcomes and professional performance. Typically,
      holistic tasks are used to train, practice and assess the defined outcomes or
      competencies. In residency training, these tasks are part of the day-to-day
      clinical practice. The performance of residents in the workplace needs to be
      captured and stored. A portfolio has been used as an instrument for storage and
      collection of workplace-based assessment and feedback in various countries, like
      the Netherlands and the United States. The collection of information in a
      portfolio can serve or be used for a variety of purposes. These are: The
      collection of work samples, assessment, feedback and evaluations in a portfolio
      enables the learner to look back, analyze and reflect. The content is used for
      assessment or making decisions about progress. And the portfolio is used as an
      instrument for quality assurance processes. In post-graduate medical education,
      these purposes can be combined but this is not always reported transparently. In
      this paper, we will discuss the different perspectives, how a portfolio can serve
      these three purposes and what are opportunities and challenges of combining
      multiple purposes.

PMID- 29226226
TI  - Work-based Assessment and Co-production in Postgraduate Medical Training.
AB  - Assessment has always been an essential component of postgraduate medical
      education and for many years focused predominantly on various types of
      examinations. While examinations of medical knowledge and more recently of
      clinical skills with standardized patients can assess learner capability in
      controlled settings and provide a level of assurance for the public, persistent
      and growing concerns regarding quality of care and patient safety worldwide has
      raised the importance and need for better work-based assessments. Work-based
      assessments, when done effectively, can more authentically capture the abilities
      of learners to actually provide safe, effective, patient-centered care.
      Furthermore, we have entered the era of interprofessional care where effective
      teamwork among multiple health care professionals is now paramount. Work-based
      assessment methods are now essential in an interprofessional healthcare world. To
      better prepare learners for these newer competencies and the ever-growing
      complexity of healthcare, many post-graduate medical education systems across the
      globe have turned to outcomes-based models of education, codified through
      competency frameworks. This commentary provides a brief overview on key methods
      of work-based assessment such as direct observation, multisource feedback,
      patient experience surveys and performance measures that are needed in a
      competency-based world that places a premium on educational and clinical
      outcomes. However, the full potential of work-based assessments will only be
      realized if post-graduate learners play an active role in their own assessment
      program. This will require a substantial culture change, and culture change only
      occurs through actions and changed behaviors. Co-production offers a practical
      and philosophical approach to engaging postgraduate learners to be active,
      intrinsically motivated agents for their own professional development, help to
      change learning culture and contribute to improving programmatic assessment in
      post-graduate training.

PMID- 29226227
TI  - Online Platform as a Tool to Support Postgraduate Training in General Practice -
      A Case Report.
AB  - Objective: Physicians in postgraduate training (PPT) in General Practice (GP)
      typically have very little interaction with their peers, as there is usually only
      one resident physician working in their respective department or GP office at a
      given time. Therefore, the online platform KOLEGEA, presented here, aims to
      support postgraduate training in general practice (PT in GP) in Germany through
      virtual interaction. Methodology: In 2012, the interdisciplinary research project
      KOLEGEA set up an online platform that any physicians in PT in GP can use for
      free after registration with their unitary continuous education number
      (Einheitliche Fortbildungsnummer, EFN). It offers problem-based learning and
      allows to discuss self-published anonymized patient cases with the community that
      can be classified and discussed with experienced mentors (specialists in general
      practice - GPs) in small virtual groups. Results: An anonymous online survey
      carried out as part of the 2014 project evaluation showed a good acceptance of
      the platform, even though shortage of time was mentioned as a limiting factor for
      its use. Data analysis showed that KOLEGEA was used by PPT in GP in all federal
      states. Patterns of passive use were predominant (90%). This report also
      describes the further development of the platform (in 2015 and 2016) that
      integrates an activity monitor as part of a gamification concept. Conclusions:
      Due to a low response rate of the 2014 online survey and the preliminary
      evaluations of usage patterns we could identify only initial trends regarding the
      role of KOLEGEA in supporting PPT. The platform was perceived as a helpful
      supplement to better structure PT in GP.

PMID- 29226228
TI  - Seminar program for postgraduate specialty training in general practice: proposal
      for a 5-year thematic catalogue.
AB  - Introduction: In different German regions, seminar programs have been conducted
      for General practice residents. In each region, selection and teaching of
      learning content is conducted in a different manner. So far, no structured,
      standardized curriculum has been implemented nationwide. We have investigated, if
      the development of a common 5-year program of learning topics is conceivable
      between the different university departments of General practice in Germany.
      Method: The seminar program working group of the DEGAM (German College of General
      Practitioners and Family Physicians) has conducted an online survey based on
      information gathered via preliminary telephone conference (n=7; physicians with
      postgraduate teaching experience) among all German university departments of
      General Practice and two non-university teaching institutions, identified via the
      internet. 884 topics were extracted from 14 Seminar programs. The topics were
      entered in a database, discussed and categorized: Practice management/practice
      work flow/standardized documentation forms/quality management (n=33 topics),
      common acute and chronic diseases, including disease management programs (n=29
      topics), communication, neurological, psychological and psychiatric consultations
      (n=24 topics), common medical problems, including eye, ear, nose, throat, skin
      and pediatric problems (n=99 Topics) family physicians general approach,
      including epidemiology, shared decision making, test of time (n=42 Topics). These
      topics have been rated for priority and desirable number of teaching-units.
      Results: A catalogue of 111 topics was designed, encompassing 160 teaching units.
      There is a suggestion of wide topics collections plus an add-on catalogue.
      Conclusion: A proposal for a 5-year-thematic catalogue for postgraduate training
      of general practice residents in Germany has been developed. This newly developed
      curriculum has the potential to improve knowledge and skills that have not been
      covered during in-house and ambulatory general practice residencies.

PMID- 29226229
TI  - Subspecialisation in Emergency Radiology: Proposal for a harmonised European
      curriculum.
AB  - Introduction: Radiology plays a crucial role in the emergency care setting by
      delivering early and precise diagnoses under pressure of time, right at the
      beginning of patient treatment. Although there is a need for postgraduate
      education in emergency radiology, most of the national bodies responsible do not
      offer it in a uniform fashion and a general proof of qualification is missing in
      Europe. Therefore, the European Society of Radiology (ESR) has founded the (Sub
      )Society of Emergency Radiology (ESER), prompting them to develop a European
      curriculum. This trend, which is currently also encouraged in many other non
      radiological specialties which demand the highest professional qualifications,
      often lacks expertise in medical education. Goals: The goal of this article is
      the general description of the curricular planning process for a European
      postgraduate subspecialisation programme, using the example of Emergency
      Radiology (European Diploma in Emergency Radiology, EDER), including the
      utilisation of TOOLS and recommendations derived from comparable projects.
      Project description: The project was divided into partial steps: the timeline
      displayed in a GANTT chart, and tasks and responsibilities assigned in a RASCI
      matrix. The curriculum was iteratively developed using the KERN approach and
      steps were prioritised using the PARETO principle. Furthermore, the following
      TOOLS were used: limitations and needs assessment, SWOT analysis, formulating
      learning objectives and categorising them after MILLER and SCLO, and using
      BLOOM's taxonomy for cognitive learning objectives and operationalising them
      according to MAGER. Psychomotoric and affective learning objectives were assigned
      to CANMEDS roles, grouped by topic using CLUSTERING, and then mapped by MATRIX
      analysis to appropriate learning and evaluation methods. Striving for continuous
      improvement, the curriculum was finally embedded in curricular quality
      management. Results: The standardisation of the EDER access, considering the
      different national conditions, the minimisation of European learners' attendance
      phases, restricting expenses by best possible use of existing structures,
      respecting the requirements and retaining the support of the European umbrella
      society ESR, finishing the project by a specific deadline and the demands of
      continuous improvement were particular challenges. A curriculum with the
      eligibility of five years' speciality training in general radiology has evolved
      on schedule. The subspeciality training lasts at least one year and is divided
      into webinars, workshops during congresses (e.g. the annual ESR and ESER
      congresses) and one year practical training at the individual learner's
      corresponding local hospitals, which adhere to a catalogue of requirements,
      comparable to national educational policies. The curriculum is completed by
      passing a written and oral exam (diploma) and re-accreditation every five years.
      Conclusions: Despite complex requirements, the TOOLS utilised allowed an almost
      seamless, resource-minimised, professional, location-independent distributed
      development of a European subspeciality curriculum within one year. The
      definitive implementation is still due. If any deviations from the draft
      presented should become necessary in the future, the embedment in the curricular
      quality management will lead to a redirection in the right way and, furthermore,
      secure a continuous improvement in the best way possible.

PMID- 29226230
TI  - New paths in post-graduate medical training in general practice - 8 years of
      experience with the pilot project Verbundweiterbildungplus Baden-Wurttemberg.
AB  - Background: In face of the looming shortage of general practitioners, primary
      healthcare providers and post-graduate training in general practice are
      increasingly becoming part of the political agenda in Germany. In 2009 the
      program "Verbundweiterbildung plus Baden-Wurttemberg" (VWB plus BW) was developed
      by the Competence Center for General Practice in Baden-Wuerttemberg to ensure
      primary healthcare in the future by enhancing the attractiveness of general
      medicine. This paper describes the experiences that have been gathered in
      developing a post-graduate training-program for physicians undergoing specialist
      training in general practice. Project description: The Competence Center for
      General Practice in Baden-Wuerttemberg supports the organization of regional
      networks dedicated to post-graduate medical education. First core element of the
      VWB plus BW program is a special seminar series for physicians pursuing post
      graduate training. This seminar program is aligned with the German competency
      based curriculum in general medicine and is meant to promote medical expertise
      and other related competencies, such as business and medical practice management
      and communication skills. Mentoring and advising the physicians regarding
      professional and personal planning form the second core element. The third core
      element is seen in the train-the-trainer seminars that address the competencies
      of the trainers. In order to focus the program's content closely on the needs of
      the target groups, scientifically based evaluations and research are carried out.
      Results: Since starting in 2009, 685 physicians have entered the program and 141
      have passed the examination to become medical specialists (as of December 2016).
      In total, 31 networks, 60 hospitals and 211 general practices have participated.
      The seminar sessions have been rated on average with 1.43 on a six-point Likert
      scale by the physician trainees (1=extremely satisfied, 6=extremely
      dissatisfied). Alongside the medical training, these physicians viewed the
      exchange of information and experiences with other physicians as very positive
      and important. In 185 seminars lasting 90 minutes each, the seminar program has
      presently covered 250 out of 320 units in the competency-based curriculum for
      general medicine. A total of 281 trainers have been trained in 13 train-the
      trainer courses and have rated this course on average with 1.36 on a six-point
      Likert scale. Above all, the trainers emphasized the exchange of information and
      experiences with other trainers as very positive. In 2013 the DEGAM concept for
      its Verbundweiterbildungplus program was developed based on that of the VWB plus
      BW. Since 2008 over 40 articles on the topic of post-graduate medical education
      have been published. Conclusion: The steadily increasing number of participants
      over the years demonstrates that the VWB plus BW is relevant for recent medical
      graduates and contributes to the attractiveness of general practice. The
      consistently excellent evaluations of the training program and the train-the
      trainer course affirm the focus on the needs of the target groups. The post
      graduate VWB plus BW program advances structured, competency-based and quality
      oriented specialist training and fosters professional sharing between physicians 
      something that could also be relevant for other fields. The increasing numbers
      of participating physicians and specialists in general practice in Baden
      Wurttemberg lead to the conclusion that the VWB plus BW program positively
      influences the number of general practitioners.

PMID- 29226231
TI  - The postgraduate medical education pathway: an international comparison.
AB  - An at first sight seemingly coherent, global medical workforce, with clearly
      recognizable specialities, subspecialties and primary care doctors, appears at a
      closer look quite variable. Even within the most progressive countries as to the
      development of medical education, with educators who regularly meet at
      conferences and share major journals about medical education, the differences in
      structures and regulations are big. This contribution focuses on the preparation,
      admission policy, duration, examinations, and national competency frameworks in
      postgraduate speciality training in Germany, the USA, Canada, the UK, Australia
      and the Netherlands. While general objectives for postgraduate training programs
      have not been very clear, only recently competency-frameworks, created in a
      limited number of countries, serve harmonize objectives. This process appears to
      be a challenge and the recent creation of milestones for the reporting on
      progress of individual trainees (in the US and in Canada in different ways) and
      the adoption of entrustable professional activities, a most recent concept that
      is quickly spreading internationally as a framework for teaching and assessing in
      the clinical workplace is an interesting and hopeful development, but time will
      tell whether true harmonization across countries will happen.

PMID- 29226232
TI  - Connecting undergraduate and postgraduate medical education through an elective
      EPA-based transitional year in acute care: an early project report.
AB  - Objective: A well-designed final year may ease the transition from medical school
      to postgraduate training, if it has enough depth to enable the acquisition of
      early specialty expertise, while keeping enough breadth to support the graduation
      as all-round physician. Aim of this article is to describe the design of a
      multidisciplinary dedicated transitional year (DTY) around the theme of
      recognition and initial treatment of vitally threatened patients. Methods:
      Undergraduate and postgraduate training directors from the departments of
      Anaesthesiology, Cardiology, Emergency Medicine, Intensive Care Medicine and
      Respiratory Medicine at UMC Utrecht and partnering hospitals have collaboratively
      developed and implemented a curriculum for a final year focusing on three
      entrustable professional activities (EPAs) in the domain of acute care. These
      EPAs represent authentic tasks of starting residents in each of the participating
      specialties, align student training objectives with postgraduate expectations,
      and are the primary focus of learning, teaching, and assessment throughout the
      year. Students are developmentally supported by a mentor and educationally
      supported by monthly academic half days. Results: Between October 2014 and
      November 2016,, 47 students chose DTY Acute Care. The set-up of our DTY is
      inspiring other specialties to develop multidisciplinary DTYs. Attainment of
      clinical competence, experience of students and staff, and exploration of
      graduates' early careers are subjects of current research projects. Conclusion:
      This multidisciplinary dedicated transitional year aims to graduate students with
      profile-specific competence in acute care. It prepares for residency in a range
      of specialties.

PMID- 29226233
TI  - Medical students' preparation for the transition to postgraduate training through
      final year elective rotations.
AB  - Objectives: This study adds to the ongoing discussion on how to ease the
      transition from undergraduate medical training to postgraduate training. In the
      Netherlands there is no central matching system for admission to residency.
      Medical school graduates just apply for a position in an open job market. Many
      choose to acquire general or specialty-specific clinical experiences after the
      medical degree before residency, to further explore career opportunities and to
      increase their chances to get into their preferred specialty. To shorten this gap
      between undergraduate and the start of postgraduate training, the sixth and final
      year of most Dutch medical schools is designed as a "transitional year". Students
      work with more clinical responsibilities than in the earlier clerkships, and this
      year includes many elective options. Our study focuses on these elective options
      and explores how medical students use these transitional year electives to
      prepare for transition to postgraduate training. Methods: In 2012-2013 we asked
      all 274 graduating students at one Dutch medical school to complete an open
      answer questionnaire with the following topics: their preferred specialty at the
      start of the transitional year, electives they chose during this year and reasons
      for these choices, and whether the transitional year electives changed their
      career considerations. Questionnaire results were coded by two researchers and
      were discussed with all members of the research team. Results: A total of 235
      students responded (86%). Answers about motivation for choices revealed that most
      electives where chosen for career orientation and to optimize chances to get into
      a residency program. Students also focused on additional experiences in
      specialties related to their preferred specialty. Many students chose electives
      logically related to each other, e.g. combinations of surgery and radiology.
      About two-thirds of the respondents stated that their elective experiences did
      confirm their specialty preferences or resulted in a more clear insight.
      Conclusion: We conclude that students use the transitional year electives to
      focus on their future postgraduate training program, i.e. for orientation and to
      align their curriculum vitae with their preferred specialty, resulting in
      spontaneous early specialty streaming. To take advantages of this streaming, and
      to make sure students can transfer their experiences to other specialties if
      their career preferences change, individual elective Entrustable Professional
      Activities (EPAs), next to the core EPAs for all medical students, may serve to
      prepare a smooth transition to a specialty of choice and should be fully
      documented.

PMID- 29226234
TI  - Implementation of a Clinical Reasoning Course in the Internal Medicine trimester
      of the final year of undergraduate medical training and its effect on students'
      case presentation and differential diagnostic skills.
AB  - Background: Clinical reasoning, comprising the processes of clinical thinking,
      which form the basis of medical decisions, constitutes a central competence in
      the clinical routine on which diagnostic and therapeutic steps are based. In
      medical curricula in Germany, clinical reasoning is currently taught explicitly
      only to a small extend. Therefore, the aim of this project was to develop and
      implement a clinical reasoning course in the final year of undergraduate medical
      training. Project description: A clinical reasoning course with six learning
      units and 18 learning objectives was developed, which was taught by two to four
      instructors on the basis of 32 paper cases from the clinical practice of the
      instructors. In the years 2011 to 2013, the course of eight weeks with two hours
      per week was taught seven times. Before the first and after the last seminar, the
      participating students filled out a self-assessment questionnaire with a 6-point
      Likert scale regarding eight different clinical reasoning skills. At the same
      times, they received a patient case with the assignment to prepare a case
      presentation and differential diagnoses. Results: From 128 participating students
      altogether, 42 complete data sets were available. After the course, participants
      assessed themselves significantly better than before the course in all eight
      clinical reasoning skills, for example in "Summarizing and presentation of a
      paper case" or in the "Skill to enumerate differential diagnoses" (p<0.05). The
      greatest increase occurred in the skill to recognize typical cognitive errors in
      medicine and to identify risk situations for their occurrence (pre: 2.98+/-0.92
      and retro-pre: 2.64+/-1.01, respectively, versus post: 4.38+/-0.88). Based on the
      ratio of number of words used per keywords used the problem presentation of the
      paper case was significantly more focused after the course (p=0.011). A
      significant increase in the number of gathered differential diagnoses was not
      detected after the course. Conclusion: The newly developed and established
      Clinical Reasoning Course leads to a gain in the desired skills from the
      students' self-assessment perspective and to a more structured case presentation.
      To establish better options to exercise clinical reasoning, a longitudinal
      implementation in the medical curriculum seems to be desirable. Faculty training
      would be useful to implement the concept as standardized as possible.

PMID- 29226235
TI  - Entrustable professional activities in post-licensure training in primary care
      pediatrics: Necessity, development and implementation of a competency-based post
      graduate curriculum.
AB  - There is an absence of broad-based and binding curricular requirements for
      structured competency-based post-graduate medical training in Germany, and thus
      no basis for comparing the competencies of physicians undergoing training in a
      medical specialty (Arzte im Weiterbildung). In response, the German Society of
      Primary Care Pediatrics' working group on post-graduate education (DGAAP) has
      identified realistic entrustable professional activities (EPAs) in primary care,
      defined their number, scope and content, selected competency domains, specified
      required knowledge and skills, and described appropriate assessment methods.
      These guidelines are referred to as PaedCompenda and can be accessed
      electronically by educators in pediatric medicine; the use and effectiveness of
      these guidelines are monitored by the German Association for Medical Education's
      committee on post-graduate education (GMA). Teaching and training in pediatric
      medicine should take EPAs into consideration. To accomplish this, phases
      dedicated to primary care should be integrated into formal medical specialty
      training. Primary care pediatrics must enhance the sites where such training
      takes place into learning environments that prepare physicians trainees and turn
      the practicing specialists into mentoring educators.

PMID- 29226236
TI  - Self-Assessment of competence during post-graduate training in general medicine:
      A preliminary study to develop a portfolio for further education.
AB  - Awareness of one's own strengths and weaknesses is a key qualification for the
      specialist physician. We examined how physicians undergoing specialist training
      in general medicine rate themselves in different areas. For this purpose, 139
      participants receiving post-graduate training in general practice offered by the
      Medical Association of Westfalen-Lippe assessed themselves regarding their
      subjective confidence in 20 core competencies and 47 situations involving patient
      counseling in general practice. Their self-assessments were recorded on a five
      point Likert scale. The study questions addressed acceptance and practicability
      of self-assessment, mean values, reliability, stratification and plausibility of
      the results in group comparison. On average participants rated their subjective
      confidence with 3.4 out of 5 points. The results are self-consistent (Cronbach's
      alpha >0.8), although there are considerable differences among competencies and
      among participants. The latter can be explained partly by biographical data,
      which supports the plausibility of the data. Participants stated that regularly
      gathering data on subjective learning needs and the discussion of these needs
      with mentors and trainers contributes to improving their specialist training.
      Elements for self-assessment are suitable for integration into a postgraduate
      training portfolio. These should be supplemented by formative assessment
      procedures.

PMID- 29226238
TI  - Postgraduate Medical Education - an increasingly important focus of study and
      innovation.

PMID- 29226237
TI  - Competency-Based Postgraduate Medical Education: Past, Present and Future.
AB  - Since the turn of the twenty-first century, competency-based medical education
      (CBME) has become a dominant approach to postgraduate medical education in many
      countries. CBME has a history dating back half a century and is rooted in general
      educational approaches such as outcome-based education and mastery learning.
      Despite controversies around the terminology and the CBME approach, important
      national medical regulatory bodies in Canada, the United States, and other
      countries have embraced CBME. CBME can be characterized as having two distinct
      features: a focus on specific domains of competence, and a relative independence
      of time in training, making it an individualized approach that is particularly
      applicable in workplace training. It is not the length of training that
      determines a person's readiness for unsupervised practice, but the attained
      competence or competencies. This shift in focus makes CBME different from
      traditional training. In this contribution, definitions of CBME and related
      concepts are detailed.

PMID- 29226239
TI  - Deconstructing the Tissue Engineered Vascular Graft: Evaluating Scaffold Pre
      Wetting, Conditioned Media Incubation, and Determining the Optimal Mononuclear
      Cell Source.
AB  - Stenosis limits widespread use of tissue-engineered vascular grafts (TEVGs), and
      bone marrow mononuclear cell (BM-MNC) seeding attenuates this complication. Yet
      seeding is a multistep process, and the singular effects of each component are
      unknown. We investigated which components of the clinical seeding protocol confer
      graft patency and sought to identify the optimal MNC source. Scaffolds composed
      of polyglycolic acid and epsilon-caprolactone/iota-lactic acid underwent
      conditioned media (CM) incubation (n = 25) and syngeneic BM-MNC (n = 9) or
      peripheral blood (PB)-MNC (n = 20) seeding. TEVGs were implanted for 2 weeks in
      the mouse IVC. CM incubation and PB-MNC seeding did not increase graft patency
      compared to control scaffolds prewet with PBS (n = 10), while BM-MNC seeding
      reduced stenosis by suppressing inflammation and smooth muscle cell,
      myofibroblast, and pericyte proliferation. IL-1beta, IL-6, and TNFalpha were
      elevated in the seeded BM-MNC supernatant. Further, BM-MNC seeding reduced
      platelet activation in a dose-dependent manner, possibly contributing to TEVG
      patency.

PMID- 29226240
TI  - Optical computed tomography for spatially isotropic four-dimensional imaging of
      live single cells.
AB  - Quantitative three-dimensional (3D) computed tomography (CT) imaging of living
      single cells enables orientation-independent morphometric analysis of the
      intricacies of cellular physiology. Since its invention, x-ray CT has become
      indispensable in the clinic for diagnostic and prognostic purposes due to its
      quantitative absorption-based imaging in true 3D that allows objects of interest
      to be viewed and measured from any orientation. However, x-ray CT has not been
      useful at the level of single cells because there is insufficient contrast to
      form an image. Recently, optical CT has been developed successfully for fixed
      cells, but this technology called Cell-CT is incompatible with live-cell imaging
      due to the use of stains, such as hematoxylin, that are not compatible with cell
      viability. We present a novel development of optical CT for quantitative,
      multispectral functional 4D (three spatial + one spectral dimension) imaging of
      living single cells. The method applied to immune system cells offers truly
      isotropic 3D spatial resolution and enables time-resolved imaging studies of
      cells suspended in aqueous medium. Using live-cell optical CT, we found a
      heterogeneous response to mitochondrial fission inhibition in mouse macrophages
      and differential basal remodeling of small (0.1 to 1 fl) and large (1 to 20 fl)
      nuclear and mitochondrial structures on a 20- to 30-s time scale in human
      myelogenous leukemia cells. Because of its robust 3D measurement capabilities,
      live-cell optical CT represents a powerful new tool in the biomedical research
      field.

PMID- 29226241
TI  - Raman spectroscopy imaging reveals interplay between atherosclerosis and medial
      calcification in the human aorta.
AB  - Medial calcification in the human aorta accumulates during aging and is known to
      be aggravated in several diseases. Atherosclerosis, another major cause of
      cardiovascular calcification, shares some common aggravators. However, the
      mechanisms of cardiovascular calcification remain poorly understood. To elucidate
      the relationship between medial aortic calcification and atherosclerosis, we
      characterized the cross-sectional distributions of the predominant minerals in
      aortic tissue, apatite and whitlockite, and the associated extracellular matrix.
      We also compared the cellular changes between atherosclerotic and
      nonatherosclerotic human aortic tissues. This was achieved through the
      development of Raman spectroscopy imaging methods that adapted algorithms to
      distinguish between the major biomolecules present within these tissues. We
      present a relationship between apatite, cholesterol, and triglyceride in
      atherosclerosis, with the relative amount of all molecules concurrently increased
      in the atherosclerotic plaque. Further, the increase in apatite was
      disproportionately large in relation to whitlockite in the aortic media directly
      underlying a plaque, indicating that apatite is more pathologically significant
      in atherosclerosis-aggravated medial calcification. We also discovered a
      reduction of beta-carotene in the whole aortic intima, including a plaque in
      atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This
      unprecedented biomolecular characterization of the aortic tissue furthers our
      understanding of pathological and physiological cardiovascular calcification
      events in humans.

PMID- 29226242
TI  - Intracerebroventricular delivery of hematopoietic progenitors results in rapid
      and robust engraftment of microglia-like cells.
AB  - Recent evidence indicates that hematopoietic stem and progenitor cells (HSPCs)
      can serve as vehicles for therapeutic molecular delivery to the brain by
      contributing to the turnover of resident myeloid cell populations. However, such
      engraftment needs to be fast and efficient to exert its therapeutic potential for
      diseases affecting the central nervous system. Moreover, the nature of the cells
      reconstituted after transplantation and whether they could comprise bona fide
      microglia remain to be assessed. We demonstrate that transplantation of HSPCs in
      the cerebral lateral ventricles provides rapid engraftment of morphologically,
      antigenically, and transcriptionally dependable microglia-like cells. We show
      that the cells comprised within the hematopoietic stem cell compartment and
      enriched early progenitor fractions generate this microglia-like population when
      injected in the brain ventricles in the absence of engraftment in the bone
      marrow. This delivery route has therapeutic relevance because it increases the
      delivery of therapeutic molecules to the brain, as shown in a humanized animal
      model of a prototypical lysosomal storage disease affecting the central nervous
      system.

PMID- 29226243
TI  - Single-frame 3D fluorescence microscopy with ultraminiature lensless FlatScope.
AB  - Modern biology increasingly relies on fluorescence microscopy, which is driving
      demand for smaller, lighter, and cheaper microscopes. However, traditional
      microscope architectures suffer from a fundamental trade-off: As lenses become
      smaller, they must either collect less light or image a smaller field of view. To
      break this fundamental trade-off between device size and performance, we present
      a new concept for three-dimensional (3D) fluorescence imaging that replaces
      lenses with an optimized amplitude mask placed a few hundred micrometers above
      the sensor and an efficient algorithm that can convert a single frame of captured
      sensor data into high-resolution 3D images. The result is FlatScope: perhaps the
      world's tiniest and lightest microscope. FlatScope is a lensless microscope that
      is scarcely larger than an image sensor (roughly 0.2 g in weight and less than 1
      mm thick) and yet able to produce micrometer-resolution, high-frame rate, 3D
      fluorescence movies covering a total volume of several cubic millimeters. The
      ability of FlatScope to reconstruct full 3D images from a single frame of
      captured sensor data allows us to image 3D volumes roughly 40,000 times faster
      than a laser scanning confocal microscope while providing comparable resolution.
      We envision that this new flat fluorescence microscopy paradigm will lead to
      implantable endoscopes that minimize tissue damage, arrays of imagers that cover
      large areas, and bendable, flexible microscopes that conform to complex
      topographies.

PMID- 29226244
TI  - Transport properties of carbonated silicate melt at high pressure.
AB  - Carbon dioxide, generally considered as the second most abundant volatile
      component in silicate magmas, is expected to significantly influence various melt
      properties. In particular, our knowledge about its dynamical effects is lacking
      over most of Earth's mantle pressure regime. Here, we report the first-principles
      molecular dynamics results on the transport properties of carbonated MgSiO3
      liquid under conditions of mantle relevance. They show that dissolved CO2
      systematically enhances the diffusion rates of all elements and lowers the melt
      viscosity on average by factors of 1.5 to 3 over the pressure range considered.
      It is remarkable that CO2 has very little or no influence on the electrical
      conductivity of the silicate melt under most conditions. Simulations also predict
      anomalous dynamical behavior, increasing diffusivity and conductivity and
      decreasing viscosity with compression in the low-pressure regime. This anomaly
      and the concomitant increase of pressure and temperature with depth together make
      these transport coefficients vary modestly over extended portions of the mantle
      regime. It is possible that the melt electrical conductivity under conditions
      corresponding to the 410- and 660-km seismic discontinuities is at a detectable
      level by electromagnetic sounding observation. In addition, the low melt
      viscosity values of 0.2 to 0.5 Pa?s at these depths and near the core-mantle
      boundary may imply high mobility of possible melts in these regions.

PMID- 29226245
TI  - Multivalent ions induce lateral structural inhomogeneities in polyelectrolyte
      brushes.
AB  - Subtle details about a polyelectrolyte's surrounding environment can dictate its
      structural features and potential applications. Atomic force microscopy (AFM),
      surface forces apparatus (SFA) measurements, and coarse-grained molecular
      dynamics simulations are combined to study the structure of planar
      polyelectrolyte brushes [poly(styrenesulfonate), PSS] in a variety of solvent
      conditions. More specifically, AFM images provide a first direct visualization of
      lateral inhomogeneities on the surface of polyelectrolyte brushes collapsed in
      solutions containing trivalent counterions. These images are interpreted in the
      context of a coarse-grained molecular model and are corroborated by accompanying
      interaction force measurements with the SFA. Our findings indicate that lateral
      inhomogeneities are absent from PSS brush layers collapsed in a poor solvent
      without multivalent ions. Together, AFM, SFA, and our molecular model present a
      detailed picture in which solvophobic and multivalent ion-induced effects work in
      concert to drive strong phase separation, with electrostatic bridging of
      polyelectrolyte chains playing an essential role in the collapsed structure
      formation.

PMID- 29226246
TI  - Global patterns of dust and bedrock nutrient supply to montane ecosystems.
AB  - A global compilation of erosion rates and modeled dust fluxes shows that dust
      inputs can be a large fraction of total soil inputs, particularly when erosion is
      slow and soil residence time is therefore long. These observations suggest that
      dust-derived nutrients can be vital to montane ecosystems, even when nutrient
      supply from bedrock is substantial. We tested this hypothesis using neodymium
      isotopes as a tracer of mineral phosphorus contributions to vegetation in the
      Sierra Nevada, California, where rates of erosion and dust deposition are both
      intermediate within the global compilation. Neodymium isotopes in pine needles,
      dust, and bedrock show that dust contributes most of the neodymium in vegetation
      at the site. Together, the global data sets and isotopic tracers confirm the
      ecological significance of dust in eroding mountain landscapes. This challenges
      conventional assumptions about dust-derived nutrients, expanding the plausible
      range of dust-reliant ecosystems to include many temperate montane regions,
      despite their relatively high rates of erosion and bedrock nutrient supply.

PMID- 29226247
TI  - In operando x-ray imaging of nanoscale devices: Composition, valence, and
      internal electrical fields.
AB  - We introduce a method for directly imaging depletion layers in operando with
      elemental specificity and chemical speciation at sub-100 nm spatial resolution
      applicable to today's three-dimensional electronic architectures. These typically
      contain complex, multicomponent designs consisting of epitaxial heterostructures,
      buried domains, or nanostructures with different shapes and sizes. Although the
      variety of devices is immense, they commonly rely on carrier separation in a
      built-in potential induced by composition or strain gradients. To image these, we
      scanned a focused synchrotron x-ray nanobeam over a single semiconductor nanowire
      heterostructure and simultaneously measured the current through the device and
      the emitted characteristic x-rays as a function of the incoming hard x-ray
      energy. With these results, it is possible to identify the compositional and
      molecular structure as well as localize the electrical fields present under
      typical working conditions. This information allows us to draw an energy band
      diagram consistent with the elemental distribution and a high-resolution chemical
      speciation map.

PMID- 29226248
TI  - Deep tissue optical focusing and optogenetic modulation with time-reversed
      ultrasonically encoded light.
AB  - Noninvasive light focusing deep inside living biological tissue has long been a
      goal in biomedical optics. However, the optical scattering of biological tissue
      prevents conventional optical systems from tightly focusing visible light beyond
      several hundred micrometers. The recently developed wavefront shaping technique
      time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light
      delivery to targeted locations beyond the optical diffusion limit. However, until
      now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We
      present the first example of TRUE focusing in 2-mm-thick living brain tissue and
      demonstrate its application for optogenetic modulation of neural activity in 800
      MUm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE
      focusing enabled precise control of neuron firing and increased the spatial
      resolution of neuronal excitation fourfold when compared to conventional lens
      focusing. This work is an important step in the application of TRUE focusing for
      practical biomedical uses.

PMID- 29226249
TI  - Direct N-alkylation of unprotected amino acids with alcohols.
AB  - N-alkyl amino acids find widespread application as highly valuable, renewable
      building blocks. However, traditional synthesis methodologies to obtain these
      suffer from serious limitations, providing a major challenge to develop
      sustainable alternatives. We report the first powerful catalytic strategy for the
      direct N-alkylation of unprotected alpha-amino acids with alcohols. This method
      is highly selective, produces water as the only side product leading to a simple
      purification procedure, and a variety of alpha-amino acids are mono- or di-N
      alkylated, in most cases with excellent retention of optical purity. The
      hydrophobicity of the products is tunable, and even simple peptides are
      selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using
      renewable fatty alcohols is also described that represents an ideal green
      transformation for obtaining fully bio-based surfactants.

PMID- 29226250
TI  - Tip-enhanced ablation and ionization mass spectrometry for nanoscale chemical
      analysis.
AB  - Spectroscopic methods with nanoscale lateral resolution are becoming essential in
      the fields of physics, chemistry, geology, biology, and materials science.
      However, the lateral resolution of laser-based mass spectrometry imaging (MSI)
      techniques has so far been limited to the microscale. This report presents the
      development of tip-enhanced ablation and ionization time-of-flight mass
      spectrometry (TEAI-TOFMS), using a shell-isolated apertureless silver tip. The
      TEAI-TOFMS results indicate the capability and reproducibility of the system for
      generating nanosized craters and for acquiring the corresponding mass spectral
      signals. Multi-elemental analysis of nine inorganic salt residues and MSI of a
      potassium salt residue pattern at a 50-nm lateral resolution were achieved. These
      results demonstrate the opportunity for the distribution of chemical compositions
      at the nanoscale to be visualized.

PMID- 29226252
TI  - Hemoporfin-mediated photodynamic therapy on normal vasculature: implications for
      phototherapy of port-wine stain birthmarks.
AB  - Background: Port-wine stain (PWS) birthmarks currently are treated using a pulsed
      dye laser (PDL) combined with transient cooling of the epidermis. PDL treatment
      protocols utilize short pulses of light (585 or 595 nm wavelength) to heat
      selectively the microvasculature due to absorption by intravascular hemoglobin.
      Although most patients respond to PDL therapy, few experience complete removal of
      the PWS. An alternate treatment option to PDL therapy of PWS is photodynamic
      therapy (PDT). Research groups have reported on various photosensitizers for PDT
      of PWS, including Hemoporfin, Benzoporphyrin Derivative monoacid ring A, and
      talaporfin sodium. Aim: Our aim was to evaluate, with an established preclinical
      in-vivo model, the efficacy of photodynamic therapy (PDT) with Hemoporfin to
      achieve persistent vascular shutdown. Methods: To monitor the microvasculature, a
      dorsal window chamber was surgically installed on 24 adult mice. The PDT
      excitation source emitted 150mW of 532nm light, with an irradiance of 100mW/cm2.
      A retroorbital injection of Hemoporfin (2 mg/kg) was performed to deliver the
      drug into the bloodstream. Laser irradiation was initiated immediately after
      injection. To monitor blood-flow dynamics in response to PDT, we used laser
      speckle imaging. We employed a dose-response experimental design to study the
      efficacy of Hemoporfin-mediated PDT to achieve persistent vascular shutdown
      observed on Day 7 after PDT. Results: We observed four general hemodynamic
      responses to PDT: (1) At low radiant exposures, we did not observe any persistent
      vascular shutdown; (2) at intermediate radiant exposures, we observed delayed
      vascular shutdown effect with significant change to the vascular structure; (3)
      at intermediate radiant exposures, we observed an acute vascular shutdown effect
      with gradual restoration of blood flow and no significant changes to the vascular
      structure; and (4) at high radiant exposures, we observed acute vascular shutdown
      that persisted during the entire 7-day monitoring period, with no change in
      vascular structure. With light dose-response analysis, we estimated a
      characteristic radiant exposure of 359 J/cm2 that was required to achieve
      persistent vascular shutdown observed on Day 7 after PDT. Conclusions: The
      experimental data collectively suggest that Hemoporfin-mediated PDT can achieve
      persistent vascular shutdown of normal microvasculature. However, compared with
      our previous data using Talaporfin Sodium as photosensitizer, Hemoporfin-mediated
      PDT is less efficient and requires a considerably longer (~four times)
      irradiation time. Relevance for patients: Patients with PWS lesions may benefit
      from the advantages that PDT potentially offers over conventional PDL therapy.
      PDT potentially is safer for patients of all skin types and more effective at
      treatment of recalcitrant lesions. Although clinical data suggest that Hemoporfin
      mediated PDT is a promising alternative to PDL therapy, our results suggest that
      additional study of other photosensitizers is warranted.

PMID- 29226251
TI  - Tissue-based biomarkers in prostate cancer.
AB  - Introduction: Prostate cancer is a heterogeneous disease. Existing risk
      stratification tools based on standard clinlicopathologic variables (prostate
      specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree
      of predictive ability. Advances in high-throughput sequencing has led to the
      development of several novel tissue-based biomarkers that can improve
      prognostication in prostate cancer management. Areas Covered: The authors review
      commercially-available, tissue-based biomarker assays that improve upon existing
      risk-stratification tools in several areas of prostate cancer management,
      including the appropriateness of active surveillance and aiding in decision
      making regarding the use of adjuvant therapy. Additionally, some of the obstacles
      to the widespread adoption of these biomarkers and discuss several
      investigational sources of new biomarkers are discussed. Expert Commentary: Work
      is ongoing to answer pertinent clinical questions in prostate cancer management
      including which patients should undergo biopsy, active surveillance, receive
      adjuvant therapy, and what systemic therapy is best in the first-line.
      Incorporation into novel biomarkers may allow for the incorporation of a
      'personalized' approach to management. Further validation will be required and
      questions of cost must be considered before wide scale adoption of these
      biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of
      biomarkers using currently available techniques.

PMID- 29226253
TI  - Functional outcome of non-surgical and surgical management for de novo
      degenerative lumbar scoliosis: a mean follow-up of 10 years.
AB  - Background: No studies have evaluated the long-term results of non-surgical and
      surgical management in de novo degenerative lumbar scoliosis (DNDLS). This study
      reports on the long-term functional outcome of patients being treated for DNDLS
      by non-surgical and surgical management. Methods: This is a retrospective review
      of a single center database of DNDLS patients that underwent surgical or usual
      non-surgical management between 1996 and 2007. In a total of 88 patients, 50
      (57%) underwent non-surgical and 38 (43%) surgical management. Baseline
      demographic, radiological-, clinical-, and surgical-related variables were
      collected. An Oswestry Disability Index (ODI) 2.0 questionnaire was sent to all
      patients after written informed consent. Results: Twenty-nine of 88 patients
      participated in the study, 15 (52%) had undergone surgical and 14 (48%) non
      surgical management with a mean follow-up of 10.9 years (range 8-15 years). There
      were no significant differences (p > 0.05) between non-surgical and surgical
      patients at baseline for age, body mass index, coronal Cobb angle, and clinical
      data. None of the non-surgical patients had undergone surgery during follow-up.
      In the surgical group, 40% had revision surgery. There was no significant
      difference in ODI total scores between groups at final follow-up (p = 0.649). A
      larger proportion of patients in the non-surgical group reported an ODI total
      score of <= 22, reflecting minimal disability (43 versus 20%; p = 0.245).
      Conclusions: This is the first study that describes the long-term 10-year
      functional outcome of non-surgical and surgical management in a cohort of
      patients with DNDLS. No significant difference in functional outcome was found
      between groups after a mean follow-up of 10 years. Despite the significant
      potential for selection bias, these results indicate that non-surgical management
      of patients with DNDLS may lead to adequate functional outcome after long periods
      of time, with no crossover to surgery. Further study is warranted to define which
      patients may benefit most from which management regimen.

PMID- 29226254
TI  - Empirical treatment of bacterial keratitis: an international survey of corneal
      specialists.
AB  - Background/aims: New antibiotic agents and changing susceptibility patterns may
      have changed the empirical treatment of bacterial keratitis. Our objective in
      this study was to survey cornea specialists' practice patterns in the initial
      treatment of bacterial ulcers. Methods: This study consisted of a short online
      survey emailed to members of the Cornea Society listserv for an international
      sample of cornea specialists. Data collection began July 2014 and ended October
      2014. Results: A total of 1009 surveys were emailed, and we received 140 (14%)
      responses. The majority of US clinicians surveyed (n=83, 80%) chose fortified
      antibiotics empirically, with 55% (n=57) selecting fortified vancomycin and 16%
      (n=17) using fluoroquinolone alone. International respondents were twice as
      likely to use fluoroquinolone monotherapy (31%, n=11, p=0.07) and less likely to
      use fortified vancomycin (33%, n=12, p=0.03). Forty-five per cent (n=46) of US
      respondents reported that their initial antibiotic choice covered methicillin
      resistant Staphylococcus aureus, compared with 22% (n=8) of international
      respondents (p<0.01). Overall, respondents who were concerned about availability
      of antibiotics and toxicity were 20.86 (p<0.001) and 7.48 (p<0.001) times more
      likely to choose fluoroquinolone monotherapy, respectively. If respondents'
      primary considerations were broad spectrum coverage or antibiotic resistance they
      had 7.10 (p<0.001) and 12.51 (p<0.001) times the odds of using fortified
      vancomycin, respectively. Conclusion: Practice patterns for the initial treatment
      of bacterial keratitis vary with clinicians in the USA being more likely to use
      fortified antibiotics versus fluoroquinolone monotherapy and more concerned with
      resistant organisms than their international peers.

PMID- 29226256
TI  - General and proximal associations between unpaid eldercare, time constraints and
      subjective well-being.
AB  - Using 2012/13 American Time Use Survey, we find as compared to non-caregivers,
      caregivers report less time on personal care, social activities and sports and
      more time on housework. They also report higher stress and lower happiness when
      engaged in daily activities. Further, using diary information which captures
      activities during a 24-hour window, we compare caregivers on days they provide
      care and caregivers on days they do not provide care. Caregivers report more time
      on housework and less on paid work, and higher levels of sadness when engaged in
      daily activities. This highlights proximal effects of informal caregiving, even
      for individuals already engaged in regular caregiving.

PMID- 29226255
TI  - Differential hemispheric and visual stream contributions to ensemble coding of
      crowd emotion.
AB  - In crowds, where scrutinizing individual facial expressions is inefficient,
      humans can make snap judgments about the prevailing mood by reading "crowd
      emotion". We investigated how the brain accomplishes this feat in a set of
      behavioral and fMRI studies. Participants were asked to either avoid or approach
      one of two crowds of faces presented in the left and right visual hemifields.
      Perception of crowd emotion was improved when crowd stimuli contained goal
      congruent cues and was highly lateralized to the right hemisphere. The dorsal
      visual stream was preferentially activated in crowd emotion processing, with
      activity in the intraparietal sulcus and superior frontal gyrus predicting
      perceptual accuracy for crowd emotion perception, whereas activity in the
      fusiform cortex in the ventral stream predicted better perception of individual
      facial expressions. Our findings thus reveal significant behavioral differences
      and differential involvement of the hemispheres and the major visual streams in
      reading crowd versus individual face expressions.

PMID- 29226257
TI  - Interleukin 10 modulation of neutrophil subsets infiltrating lungs during
      Streptococcus pneumoniae infection.
AB  - Interleukin-10 production and lung neutrophil infiltration are two essential
      components of the balanced immune response to pneumonia caused by Streptococcus
      pneumoniae. Here we describe the existence of two neutrophil subsets in lungs
      during experimental S. pneumoniae infection in mice, which have different size,
      granularity and expression of activation markers. During infection, both
      neutrophils subsets were increased in the lungs of IL-10 producing mice, however
      this increment was significantly higher in the absence of this cytokine. These
      results suggest that IL-10 is a key cytokine that regulates lung inflammation
      during bacterial infection caused by specific neutrophil subsets infiltrating the
      lungs.

PMID- 29226258
TI  - Photoelectrochemical performance of N-doped ZnO branched nanowire photoanodes.
AB  - A ZnO branched-nanowire (BNW) photoanode was doped with N for use in a
      photoelectrochemical cell (PEC) to generate H2 from water splitting. First, ZnO
      BNWs were synthesized by chemical bath deposition method. Two experimental
      methods were used for N-doping: the time-controlled direct-current glow discharge
      plasma (DCGDP) and the DC magnetron plasma (DCMP) methods, to optimize N-doping
      of the NW structure. X-ray photoelectron spectroscopy (XPS) provided the N
      distribution and atomic percentage in the BNWs. The XPS results confirmed that N
      distribution into ZnO BNWs occurred by N substitution of O sites in the ZnO
      structure and through well-screened molecular N2. The morphologies and structures
      of the fabricated nanostructures were investigated by field-emission scanning
      electron microscopy and X-ray diffraction respectively. The photoanode
      performance was demonstrated in photoelectrochemical studies at various power
      densities under both dark and illuminated conditions. Increasing the N amount in
      the ZnO BNWs increased the photocurrent in the PEC.

PMID- 29226259
TI  - Recreational boating site choice and the impact of water quality.
AB  - This paper examines whether water quality has an effect on recreational boating
      activity. The analysis is based on survey data collected by face-to-face
      interviews with recreational visitors to 10 waterway sites across Ireland. We
      model the respondent's choice decision to travel to a specific site for the
      purposes of beginning their recreational boating activity. Water quality data is
      from European Union Water Framework Directive monitoring stations. Across
      recreational sites, which have generally high water quality levels within our
      sample, we find that boaters favour sites with better water quality; as indicated
      by biological oxygen demand and phosphates metrics. We also find that for each
      additional 10 km distance from respondents' homes the probability that a site is
      visited declines by up to 10%. Preferences for other site attributes, such as
      boat slipways, parking and toilet facilities, were counter to expectation but
      reflects the fact that all boat users do not necessarily access or need all
      facilities provided.

PMID- 29226260
TI  - A novel rapid direct haemagglutination-inhibition assay for measurements of
      humoral immune response against non-haemagglutinating Fowlpox virus strains in
      vaccinated chickens.
AB  - : Fowlpox (FP) is a serious disease in chickens caused by Fowlpox virus (FPV).
      One method currently used to control FPV is vaccination followed by confirmation
      that antibody titres are protective using the indirect haemagglutination assay
      (IHA). The direct haemagglutination inhibition (HI) assay is not done because
      most FPV strains do not agglutinate chicken red blood cells (RBCs). A novel FPV
      strain TPV-1 which agglutinates chicken RBCs was discovered recently and enabled
      a direct HI assay to be conducted using homologous sera. This study is therefore
      aimed at assessing the direct HI assay using a recently discovered novel
      haemagglutinating FPV strain TPV-1 in chickens vaccinated with a commercial
      vaccine containing a non-haemagglutinating FPV.Chicks vaccinated with FPV at 1
      day-old had antibody geometric mean titres (GMT) of log2 3.7 at 7 days after
      vaccination and log2 8.0 at 28 days after vaccination when tested in the direct
      HI. Chickens vaccinated at 6 weeks-old had antibody geometric mean titres (GMT)
      of log2 5.0 at 7 days after vaccination and log2 8.4 at 28 days after vaccination
      when tested in the direct HI. The GMT recorded 28 days after vaccination was
      slightly higher in chickens vaccinated at 6-week-old than in chicks vaccinated at
      one-day-old. However, this difference was not significant (P > 0.05). All
      vaccinated chickens showed "takes". No antibody response to FPV and "takes" were
      detected in unvaccinated chickens (GMT < 1). There was a slightly higher GMT in
      chickens of all ages throughout the observation period when the standard assay,
      the passive (indirect) haemagglutination was used (Overall GMT reached log2 9.3
      +/-.0.3 on day 28). However, the difference between the two assays was not
      significant (P > 0.05). Conclusion: These findings indicate that a simple and
      rapid direct HI assay using the FPV TPV-1 strain as antigen may be used to
      measure antibody levels in chickens vaccinated with non-haemagglutinating strains
      of FPV, and that the titres are comparable to those obtained by indirect IHA.

PMID- 29226261
TI  - Coordination of early cellular reactions during activation of bone resorption in
      the rat mandible periosteum: An immunohistochemical study.
AB  - The activation step of bone remodeling remains poorly characterized. Activation
      comprises determination of the site to be remodeled, osteoclast precursor
      recruitment, their migration to the site of remodeling, and differentiation.
      These actions involve different compartments and cell types. The aim of this
      study was to investigate events and cell types involved during activation. We
      used a bone remodeling model in rats where extractions of the upper jaw molars
      initiate remodeling of the antagonist lower jaw (mandible) cortex along the
      periosteum. In this model osteoclastic resorption peaks 4 days after extractions.
      We previously reported that mast cell activation in the periosteum fibrous
      compartment is an early event of activation, associated with recruitment of
      circulating monocyte osteoclast precursors. By using immunohistochemistry, we
      observed 9 hours after induction a spatially oriented expression of InterCellular
      Adhesion Molecule-1 in the vessels that was inhibited by antagonists of histamine
      receptors 1 and 2. It was followed at 12 hours by the recruitment of ED1+
      monocytes. In parallel, at 9 hours, Vascular Cellular Adhesion Molecule-1+
      fibroblast-like cells scattered in the fibrous compartment of the periosteum
      between the vessels and the osteogenic compartment increased; these cells may be
      implicated in osteoclast precursor migration. Receptor Activator of NF KappaB
      Ligand+ cells increased at 12 hours in the osteogenic compartment and reached a
      peak at 18 hours. At 24 hours the numbers of osteogenic cells and subjacent
      osteocytes expressing semaphorin 3a, a repulsive for osteoclast precursors,
      decreased before returning to baseline at 48 hours. These data show that during
      activation the two periosteum compartments and several cell types are coordinated
      to recruit and guide osteoclast precursors towards the bone surface.

PMID- 29226262
TI  - Topology optimization aided structural design: Interpretation, computational
      aspects and 3D printing.
AB  - Construction industry has a major impact on the environment that we spend most of
      our life. Therefore, it is important that the outcome of architectural intuition
      performs well and complies with the design requirements. Architects usually
      describe as "optimal design" their choice among a rather limited set of design
      alternatives, dictated by their experience and intuition. However, modern design
      of structures requires accounting for a great number of criteria derived from
      multiple disciplines, often of conflicting nature. Such criteria derived from
      structural engineering, eco-design, bioclimatic and acoustic performance. The
      resulting vast number of alternatives enhances the need for computer-aided
      architecture in order to increase the possibility of arriving at a more
      preferable solution. Therefore, the incorporation of smart, automatic tools in
      the design process, able to further guide designer's intuition becomes even more
      indispensable. The principal aim of this study is to present possibilities to
      integrate automatic computational techniques related to topology optimization in
      the phase of intuition of civil structures as part of computer aided
      architectural design. In this direction, different aspects of a new computer
      aided architectural era related to the interpretation of the optimized designs,
      difficulties resulted from the increased computational effort and 3D printing
      capabilities are covered here in.

PMID- 29226263
TI  - Aerodynamic effects of dimples on soccer ball surfaces.
AB  - Recently, the shape and design of the panel on the official ball used in the FIFA
      World Cup was considerably different from that of a conventional soccer ball
      (having 32 pentagonal and hexagonal panels). Depending on the number of different
      panels and their orientation, the aerodynamic force experienced by a ball is
      believed to change, which in turn changes the ball trajectory. However, not much
      is known about the impact of the surface forms of a ball on its aerodynamics.
      Therefore, in the present study, 10 different types of soccer balls were produced
      and their aerodynamic properties were studied by wind tunnel experiments. The
      results confirmed that the aerodynamic force acting on the ball varied
      considerably depending on the existence of dimples on the ball surface. In
      addition, the 4 types of soccer balls, which had different kinds of roughness,
      revealed that even balls having the same number and shapes of panels experienced
      greatly varying aerodynamic forces depending on the surface form of the balls.

PMID- 29226264
TI  - Generation of viable progeny from dead brooders of endangered catfish Clarias
      magur (Hamilton, 1822).
AB  - The obligatory air-breathing catfish Clarias magur is a prime candidate for
      aquaculture owing to its unique taste, high growth rate, and hardy nature.
      However, recently the IUCN has listed the species under the endangered category
      because the population has critically declined in the wild. The sexually mature
      C. magur brooders are often collected from their natural habitats for seed
      production in captivity. In many cases, the brooder dies due to handling injuries
      or confinement stress. In this study, we demonstrated that viable progeny could
      be generated from freshly dead sexually mature C. magur. Three hours after death,
      the gonads were excised, macroscopically examined and gamete viability was
      evaluated. Artificial fertilization was performed by mixing the sperm suspension
      with the eggs. Water was added after 1 min of mixing to activate the
      fertilization process. We observed 85%-93% fertilization success from gametes
      derived from dead donors as opposed to 90%-95% from those derived from live
      control donors. The embryos showed normal development and resulted in the
      generation of 88%-92% viable progeny, which was similar to the progeny derived
      from control donors (92%-93%). The results obtained in this study will have
      profound implications in enhancing the seed production of endangered C. magur and
      could potentially be applied to other key commercially or endangered fish
      species.

PMID- 29226265
TI  - ST2 gene products critically contribute to cellular transformation caused by an
      oncogenic Ras mutant.
AB  - The ST2 gene was originally identified as a primary responsive gene, and the
      expressions of its gene products are induced by stimulation with growth factors
      and by oncogenic stresses. In this study, we observed that oncogenic Ras mutant
      induced the expression of ST2 and ST2L proteins. Interestingly, the enforced
      expression of ST2 gene products in NIH-3T3 murine fibroblasts remarkably enhanced
      Ras (G12V)-induced cellular transformation. Furthermore, when the expression of
      ST2 gene products was silenced by RNA-interference technique, Ras (G12V)-induced
      cellular transformation was drastically suppressed. According to these
      observations, it was indicated that the oncogenic Ras-induced expression of ST2
      gene products is required for the acceleration of cellular transformation, and
      this seems to be independent of the stimulation with IL-33, a ligand for
      ST2/ST2L. Interestingly, knockdown of ST2 gene products caused a reduction in Rb
      phosphorylation in transformed murine fibroblasts, suggesting the functional
      involvement of ST2 gene products in cell cycle progression during cellular
      transformation. Our current study strongly suggests the importance of ST2 gene
      products in cellular transformation, and the presence of novel mechanism how ST2
      gene products affect the cellular transformation and cell proliferation.

PMID- 29226266
TI  - The Influence of Race and Ethnicity on Becoming a Human Subject: Factors
      Associated with Participation in Research.
AB  - INRODUCTION: The purpose of this study was to explore factors associated with
      willingness of African Americans and Latinos to participate in biomedical and
      public health research and to delineate factors that influences the decision to
      become a human subject. METHODS: We present results from a 2010 random digit-dial
      telephone survey of 2,455 African American (N= 1,191) and Latino (N= 1,264)
      adults. We used standard measures to assess knowledge of research, terminology,
      informed consent procedures, previous participation in research, health care
      experiences, social support, risk perception, religiousness, and trust. RESULTS:
      Over 60% of both African Americans and Latinos reported they believed people in
      medical research are pressured into participating. Over 50% said that it was not
      at all important to have someone of the same race/ethnicity ask them to
      participate. In a sub-sample of 322 African Americans and 190 Latinos who had
      previously been asked to participate in a research study, 63% of African
      Americans and 65% of Latinos consented to participate in a study. Finally, both
      African Americans (57%) and Latinos (68%) reported willingness to participate in
      future research. Overall, the multivariate analysis explained 29% of the
      variability in willingness to participate in future research. CONCLUSIONS:
      Results suggest that African Americans and Latinos have no automatic
      predisposition to decline participation in research studies. These results can
      inform culturally tailored interventions for ethical recruitment of minorities
      into research and clinical trials.

PMID- 29226268
TI  - Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris
      Configuration.
AB  - Purpose: Our purpose is to describe a 60-year-old male, who has plateau iris
      configuration and developed bilateral ciliochoroidal effusion syndrome after
      ingestion of acetazolamide. Observations: Our case was a research participant in
      a multi-center clinical study (ClinicalTrials.gov NCT01677507). During the course
      of this study, he was treated with a single dose of acetazolamide (500 mg), and
      seven days later treated with latanoprost one drop daily at bedtime both eyes for
      seven days, and then was administered another dose of acetazolamide (500 mg).
      Several hours later he complained of blurred vision in the distance and mild
      headache. On examination, he had a myopic shift, intraocular pressures of 36 mmHg
      in right eye and 35 mmHg in left eye, shallow anterior chambers both eyes, and
      occluded angles by gonioscopy both eyes. An echographic exam confirmed the
      bilateral ciliochoroidal effusion syndrome. He was treated by no further dosing
      of acetazolamide and started on timolol, atropine and prednisolone. Two weeks
      later, the bilateral choroidal effusion and acute angle closure were resolved.
      Repeat echography showed plateau iris configuration. Conclusions and Importance:
      To the best of our knowledge, drug-induced bilateral ciliochoroidal effusion
      syndrome has not been reported with acetazolamide in plateau iris configuration.

PMID- 29226267
TI  - Orbitofrontal cortex activity and connectivity predict future depression symptoms
      in adolescence.
AB  - Background: Major depressive disorder is a leading cause of disability worldwide;
      however, little is known about pathological mechanisms involved in its
      development. Research in adolescent depression has focused on reward sensitivity
      and striatal mechanisms implementing it. The contribution of loss sensitivity to
      future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical
      for processing losses and rewards, remain unexplored. Furthermore, it is unclear
      whether OFC functioning interacts with familial history in predicting future
      depression. Methods: In this longitudinal study we recorded functional magnetic
      resonance imaging (fMRI) data while 229 adolescent females with or without
      parental history of depression completed a monetary gambling task. We examined if
      OFC blood-oxygen-level-dependent (BOLD) response and functional connectivity
      during loss and win feedback was associated with depression symptoms concurrently
      and prospectively (9 months later), and whether this relationship was moderated
      by parental history of depression. Results: Reduced OFC response during loss was
      associated with higher depression symptoms concurrently and prospectively, even
      after controlling for concurrent depression, specifically in adolescents with
      parental history of depression. Similarly, increased OFC-posterior insula
      connectivity during loss was associated with future depression symptoms but this
      relationship was not moderated by parental history of depression. Conclusions:
      This study provides the first evidence for loss-related alterations in OFC
      functioning and its interaction with familial history of depression as possible
      mechanisms in the development of depression. While the current fMRI literature
      has mainly focused on reward, the present findings underscore the need to include
      prefrontal loss processing in existing developmental models of depression.

PMID- 29226269
TI  - Evaluating Weathering of Food Packaging Polyethylene-Nano-clay Composites:
      Release of Nanoparticles and their Impacts.
AB  - Nano-fillers are increasingly incorporated into polymeric materials to improve
      the mechanical, barrier or other matrix properties of nanocomposites used for
      consumer and industrial applications. However, over the life cycle, these
      nanocomposites could degrade due to exposure to environmental conditions,
      resulting in the release of embedded nanomaterials from the polymer matrix into
      the environment. This paper presents a rigorous study on the degradation and the
      release of nanomaterials from food packaging composites. Films of nano-clay
      loaded low-density polyethylene (LDPE) composite for food packaging applications
      were prepared with the spherilene technology and exposed to accelerated
      weathering of ultraviolet (UV) irradiation or low concentration of ozone at 40 
      degrees C. The changes in the structural, surface morphology, chemical and
      physical properties of the films during accelerated weathering were investigated.
      Qualitative and quantitative changes in properties of pristine and aged materials
      and the release of nano-clay proceeded slowly until 130 hr irradiation and then
      accelerated afterward resulting complete degradation. Although nano-clay
      increased the stability of LDPE and improved thermal and barrier properties, they
      accelerated the UV oxidation of LDPE. With increasing exposure to UV, the surface
      roughness, chemiluminescence index, and carbonyl index of the samples increased
      while decreasing the intensity of the wide-angle X-ray diffraction pattern. Nano
      clay particles with sizes ranging from 2-8 nm were released from UV and ozone
      weathered composite. The concentrations of released nanoparticles increased with
      an increase in aging time. Various toxicity tests, including reactive oxygen
      species generation and cell activity/viability were also performed on the
      released nano-clay and clay polymer. The released nano-clays basically did not
      show toxicity. Our combined results demonstrated the degradation properties of
      nano-clay particle-embedded LDPE composites toxicity of released nano-clay
      particles to A594 adenocarcinomic human alveolar basal epithelial cells was
      observed, which will help with future risk based-formulations of exposure.

PMID- 29226270
TI  - Insights into the role of somatic mosaicism in the brain.
AB  - Somatic mosaicism refers to the fact that cells within an organism have different
      genomes. It is now clear that somatic mosaicism occurs in all brains and that
      somatic mutations in a subset of cells can cause various rare neurodevelopmental
      disorders. However, for most individuals, the extent and consequences of somatic
      mosaicism are largely unknown. The complexity and unique features of the brain
      suggest that somatic mosaicism can play an important role in behavior and
      cognition. Here we review recent manuscripts showing instances of somatic
      mosaicism in the brain and estimating its extent and possible biological
      consequences. The consequences of somatic mosaicism span vast dimensions -from a
      single-locus variant, to genes and gene networks, to cells, to the interactions
      of the mosaic cells via neural networks affecting behavior and cognition. We
      highlight how systems biology approaches are particularly well suited for the
      complex emerging field of brain somatic mosaicism.

PMID- 29226271
TI  - Clusters of Circulating Tumor Cells: a Biophysical and Technological Perspective.
AB  - The vast majority of cancer associated deaths result from metastasis, yet the
      behaviors of its most potent cellular driver, circulating tumor cell clusters,
      are only beginning to be revealed. This review highlights recent advances to our
      understanding of tumor cell clusters with emphasis on enabling technologies. The
      importance of intercellular adhesions among cells in clusters have begun to be
      unraveled with the aid of promising microfluidic strategies for isolating
      clusters from patient blood. Due to their metastatic potency, the utility of
      circulating tumor cell clusters for cancer diagnosis, drug screening, precision
      oncology and as targets of antimetastatic therapeutics are being explored. The
      continued development of tools for exploring circulating tumor cell clusters will
      enhance our fundamental understanding of the metastatic process and may be
      instrumental in devising new strategies to suppress and eliminate metastasis.

PMID- 29226272
TI  - Comparative Analysis of Lipid Extracts and Imaging Mass Spectrometry for
      Evaluating Cerebral White Matter Biochemical Pathology in an Experimental Second
      Hand Cigarette Smoke Exposure Model.
AB  - Background: White matter injury and degeneration are common features of
      developmental and aging-associated diseases, yet their pathobiological bases are
      poorly understood. However, recent advances in Matrix-Assisted Laser Desorption
      Ionization (MALDI) instruments and chemistry have provided critical tools for
      myelin-lipid analytical research. Design: This study characterizes Cigarette
      Smoke (CS) exposure effects on frontal lobe lipid ion profiles in adult male A/J
      mice that had been exposed to air for 8 weeks (A8), CS for 4 (CS4) or 8 weeks
      (CS8), or CS8 followed by 2 weeks recovery (CS8+R). MALDI data acquired by
      analysis of lipid extracts plated onto a ground steel target (high through-put)
      were compared with Imaging Mass Spectrometry (IMS). Results: MALDI-time-of-flight
      (TOF) detected 120 lipid ions with m/z's of 600 to 1300 (phospholipids and
      sulfatides) in samples plated onto the steel target or analyzed by IMS, but just
      25 ions (18%) were detected by both methods. IMS more effectively detected ions
      in the highest m/z range, whereas the extracts had abundant middle-range m/z
      ions. The experimental groups were better discriminated by PCA and R-generated
      heat map hierarchical clustering of IMS data than lipid extract data. On the
      other hand, both methods clearly delineated the CS4, CS8 and CS8+R experimental
      groups from control. Conclusions: MALDI analysis of brain lipid extracts plated
      onto a ground steel target for high through-put studies, or imaged directly in
      tissue can be used to assess biochemical pathology of white matter
      neurodegeneration and responses to treatment.

PMID- 29226274
TI  - Virtual Dissection by Ultrasound: Probe Handling in the First Year of Medical
      Education.
AB  - Objectives: The aim of the present study was to assess the educational plan of
      first-year students of medicine by analyzing their scores in ultrasound body
      scanning. Methods: Since 2009, the San Paolo Medical School (Milan, Italy) has
      vertically integrated the study of anatomy with ultrasound-assisted virtual body
      dissection. Three modules were supplied: musculoskeletal system, heart and
      abdomen pelvis. 653 first-year students were trained. The students alternated as
      mutual model and operator. A skillfulness score was assigned to each student. The
      scores were consequently listed. Nonparametric exact multiple contrast tests were
      employed to determine relative group effects. Results: Statistical analysis
      showed that: no gender-related differences were found (0:49; p=0.769); peer
      learners performed less well than peer tutors (0.677; p=0); between modules,
      scores in the musculoskeletal system (pMS=0.726) tend to be higher (p<0.001) than
      those obtained in the heart and abdomen pelvis (pH=0.398; pAP=0.375 p=0.270);
      significant differences were found compared to the beginning of the project's
      academic year. Conclusion: The students considered this didactic course an
      engaging and exciting approach. Acceptance of peer teaching was extraordinarily
      high. Autonomous exercitation allowed the students to improve self-criticism and
      enhance their own skills. The level of expertise obtained by peer tutors and by
      peer learners can be considered satisfactory. The main objective of training
      future physicians on personal stethoechoscope with the necessary competence seems
      to have been successfully started.

PMID- 29226273
TI  - Strain Elastography - How To Do It?
AB  - Tissue stiffness assessed by palpation for diagnosing pathology has been used for
      thousands of years. Ultrasound elastography has been developed more recently to
      display similar information on tissue stiffness as an image. There are two main
      types of ultrasound elastography, strain and shear wave. Strain elastography is a
      qualitative technique and provides information on the relative stiffness between
      one tissue and another. Shear wave elastography is a quantitative method and
      provides an estimated value of the tissue stiffness that can be expressed in
      either the shear wave speed through the tissues in meters/second, or converted to
      the Young's modulus making some assumptions and expressed in kPa. Each technique
      has its advantages and disadvantages and they are often complimentary to each
      other in clinical practice. This article reviews the principles, technique, and
      interpretation of strain elastography in various organs. It describes how to
      optimize technique, while pitfalls and artifacts are also discussed.

PMID- 29226275
TI  - Presentation of Gallbladder Chloroma in B-Mode Imaging and Contrast-Enhanced
      Ultrasound (CEUS) in a Patient with Acute Myelomonocytic Leukemia (AML M5).

PMID- 29226276
TI  - Letter to Editor Commenting on "Patterns of Gall Bladder Wall Thickening in
      Dengue Fever".

PMID- 29226277
TI  - Letter to Editor Commenting on "Patterns of Gall Bladder Wall Thickening in
      Dengue Fever" - Reply.

PMID- 29226278
TI  - Effects of Multiple Freeze/Thaw Cycles on Measurements of Potential Novel
      Biomarkers Associated With Adverse Pregnancy Outcomes.
AB  - World-wide, millions of women enter preterm labor or have small newborns.
      Effective biomarkers are needed to identify women at risk for these adverse
      outcomes. A time and cost effective way to examine any potentially new biomarkers
      in samples collected during prior studies or trials that had been assayed for
      other metabolites would be highly useful. Thus, the current study aimed to
      determine if samples that had been previously thawed and re-frozen could be re
      assayed for novel biomarkers, those being lipoprotein composition (sizing,
      proteome, lipids) and combined cholesterol and cytokine concentrations. Fasting
      blood was collected from 51 young non-pregnant women and plasma was analyzed for
      lipoprotein composition and cytokine concentrations after multiple freeze/thaw
      cycles in the cold or at room temperature and after being stored for 18 months.
      Plasma LDL-C, HDL-C, total cholesterol, and triglyceride concentrations decreased
      <6-7% (cholesterols) or <20% (triglyceride) after 7 thaws in the cold, 3 thaws at
      room temperature, and after 18 months of storage. As these decreases were less
      than day-to-day reported variation of lipids, they do not appear to be
      physiologically significant. Cytokine (IL-6, TNF alpha, IL-8, IL-1beta) and hsCRP
      concentrations decreased by 22%, 8%, 8%, 22%, and 35%, respectively; only IL-6,
      IL-1beta and hsCRP concentrations showed significant decreases greater than day
      to-day variations of 20%. For measured triglyceride and cytokine, but not
      cholesterol concentrations, decreases with freeze/thaw cycles were greater when
      concentrations were elevated. Multiple thaws also led to changes in lipoprotein
      sizing, specifically to a shift from medium- and large-sized HDL particles to
      small-sized HDL particles and from large LDL to IDL. No changes occurred for VLDL
      particle numbers. Though particle sizes changed, the HDL proteome did not change
      with multiple thaw cycles or after long term storage. Overall, the results
      demonstrate that it is possible to use previously obtained frozen samples for
      plasma cholesterol and triglyceride levels and the lipoprotein proteome, and
      lipoprotein sizing and cytokine concentrations if one knows the history of the
      sample as changes should be relative to one another.

PMID- 29226279
TI  - Visual-motor coordination in natural reaching of young children and adults.
AB  - The current study investigated eye-hand coordination in natural reaching. We
      asked whether the speed of reaching related to the quality of visual information
      obtained by young children and adults. Participants played with objects on a
      table while their eye and hand movements were recorded. We developed new
      techniques to find reaching events in natural activity and to determine how
      closely participants aligned gaze to objects while reaching. Reaching speed and
      eye alignment were related for adults but not for children. These results suggest
      that adults but not children adapt reaching movements according to the quality of
      visual information (or vice-versa) during natural activity. We discuss
      possibilities for why this coordination was not observed in children.

PMID- 29226280
TI  - Linking Joint Attention with Hand-Eye Coordination - A Sensorimotor Approach to
      Understanding Child-Parent Social Interaction.
AB  - An understanding of human collaboration requires a level of analysis that
      concentrates on sensorimotor behaviors in which the behaviors of social partners
      continually adjust to and influence each other. A suite of individual differences
      in partners' ability to both read the social cues of others and to send effective
      behavioral cues to others create dyad differences in joint attention and joint
      action. The present paper shows that infant and dyad differences in hand-eye
      coordination predict dyad differences in joint attention. In the study reported
      here, 51 toddlers and their parents wore head-mounted eye-trackers as they played
      together with objects. This method allowed us to track the gaze direction of each
      participant to determine when they attended to the same object. We found that
      physically active toddlers align their looking behavior with their parent, and
      achieve a high proportion of time spent jointly attending to the same object in
      toy play. However, joint attention bouts in toy play don't depend on gaze
      following but rather on the coordination of gaze with hand actions on objects.
      Both infants and parents attend to their partner's object manipulations and in so
      doing fixate the object visually attended by their partner. Thus, the present
      results provide evidence for another pathway to joint attention - hand following
      instead of gaze following. Moreover, dyad differences in joint attention are
      associated with dyad differences in hand following, and specifically parents' and
      infants' manual activities on objects and the within- and between-partner
      coordination of hands and eyes during parent-infant interactions. In particular,
      infants' manual actions on objects play a critical role in organizing parent
      infant joint attention to an object.

PMID- 29226281
TI  - Statistical Word Learning is a Continuous Process: Evidence from the Human
      Simulation Paradigm.
AB  - In the word-learning domain, both adults and young children are able to find the
      correct referent of a word from highly ambiguous contexts that involve many words
      and objects by computing distributional statistics across the co-occurrences of
      words and referents at multiple naming moments (Yu & Smith, 2007; Smith & Yu,
      2008). However, there is still debate regarding how learners accumulate
      distributional information to learn object labels in natural learning
      environments, and what underlying learning mechanism learners are most likely to
      adopt. Using the Human Simulation Paradigm (Gillette, Gleitman, Gleitman &
      Lederer, 1999), we found that participants' learning performance gradually
      improved and that their ability to remember and carry over partial knowledge from
      past learning instances facilitated subsequent learning. These results support
      the statistical learning model that word learning is a continuous process.

PMID- 29226282
TI  - Feasibility of Conducting a 6-month long Home-based Exercise Program with Protein
      Supplementation in Elderly Community-dwelling Individuals with Heart Failure.
AB  - Objective: Cardiac cachexia is a condition associated with heart failure,
      particularly in the elderly, and is characterized by loss of muscle mass with or
      without the loss of fat mass. Approximately 15% of elderly heart failure patients
      will eventually develop cardiac cachexia; such a diagnosis is closely associated
      with high morbidity and increased mortality. While the mechanism(s) involved in
      the progression of cardiac cachexia is incompletely established, certain factors
      appear to be contributory. Dietary deficiencies, impaired bowel perfusion, and
      metabolic dysfunction all contribute to reduced muscle mass, increased muscle
      wasting, increased protein degradation, and reduced protein synthesis. Thus
      slowing or preventing the progression of cardiac cachexia relies heavily on
      dietary and exercise-based interventions in addition to standard heart failure
      treatments and medications. Methods: The aim of the present study was to test the
      feasibility of an at-home exercise and nutrition intervention program in a
      population of elderly with heart failure, in an effort to determine whether
      dietary protein supplementation and increased physical activity may slow the
      progression, or prevent the onset, of cardiac cachexia. Frail elderly patients
      over the age of 55 with symptoms of heart failure from UAMS were enrolled in one
      of two groups, intervention or control. To assess the effect of protein
      supplementation and exercise on the development of cardiac cachexia, data on
      various measures of muscle quality, cardiovascular health, mental status, and
      quality of life were collected and analyzed from the two groups at the beginning
      and end of the study period. Results: More than 50% of those who were initially
      enrolled actually completed the 6-month study. While both groups showed some
      improvement in their study measures, the protein and exercise group showed a
      greater tendency to improve than the control group by the end of the six months.
      Conclusion: These findings suggest that with a larger cohort, this intervention
      may show significant positive effects for elderly patients who are at risk of
      developing cardiac cachexia.

PMID- 29226283
TI  - Improving Functional MRI Registration Using Whole-Brain Functional Correlation
      Tensors.
AB  - Population studies of brain function with resting-state functional magnetic
      resonance imaging (rs-fMRI) largely rely on the accurate inter-subject
      registration of functional areas. This is typically achieved through registration
      of the corresponding T1-weighted MR images with more structural details. However,
      accumulating evidence has suggested that such strategy cannot well-align
      functional regions which are not necessarily confined by the anatomical
      boundaries defined by the T1-weighted MR images. To mitigate this problem,
      various registration algorithms based directly on rs-fMRI data have been
      developed, most of which have utilized functional connectivity (FC) as features
      for registration. However, most of the FC-based registration methods usually
      extract the functional features only from the thin and highly curved cortical
      grey matter (GM), posing a great challenge in accurately estimating the whole
      brain deformation field. In this paper, we demonstrate that the additional useful
      functional features can be extracted from brain regions beyond the GM,
      particularly, white-matter (WM) based on rs-fMRI, for improving the overall
      functional registration. Specifically, we quantify the local anisotropic
      correlation patterns of the blood oxygenation level-dependent (BOLD) signals,
      modeled by functional correlation tensors (FCTs), in both GM and WM. Functional
      registration is then performed based on multiple components of the whole-brain
      FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM)
      algorithm. Experimental results show that our proposed method achieves superior
      functional registration performance, compared with other conventional
      registration methods.

PMID- 29226284
TI  - Gray Matter Surface based Spatial Statistics (GS-BSS) in Diffusion
      Microstructure.
AB  - Tract-based spatial statistics (TBSS) has proven to be a popular technique for
      performing voxel-wise statistical analysis that aims to improve sensitivity and
      interpretability of analysis of multi-subject diffusion imaging studies in white
      matter. With the advent of advanced diffusion MRI models - e.g., the neurite
      orientation dispersion density imaging (NODDI), it is of interest to analyze
      microstructural changes within gray matter (GM). A recent study has proposed
      using NODDI in gray matter based spatial statistics (N-GBSS) to perform voxel
      wise statistical analysis on GM microstructure. N-GBSS adapts TBSS by
      skeletonizing the GM and projecting diffusion metrics to a cortical ribbon. In
      this study, we propose an alternate approach, known as gray matter surface based
      spatial statistics (GS-BSS), to perform statistical analysis using gray matter
      surfaces by incorporating established methods of registration techniques of GM
      surface segmentation on structural images. Diffusion microstructure features from
      NODDI and GM surfaces are transferred to standard space. All the surfaces are
      then projected onto a common GM surface non-linearly using diffeomorphic spectral
      matching on cortical surfaces. Prior post-mortem studies have shown reduced
      dendritic length in prefrontal cortex region in schizophrenia and bipolar
      disorder population. To validate the results, statistical tests are compared
      between GS-BSS and N-GBSS to study the differences between healthy and psychosis
      population. Significant results confirming the microstructural changes are
      presented. GS-BSS results show higher sensitivity to group differences between
      healthy and psychosis population in previously known regions.

PMID- 29226285
TI  - Anatomically Constrained Video-CT Registration via the V-IMLOP Algorithm.
AB  - Functional endoscopic sinus surgery (FESS) is a surgical procedure used to treat
      acute cases of sinusitis and other sinus diseases. FESS is fast becoming the
      preferred choice of treatment due to its minimally invasive nature. However, due
      to the limited field of view of the endoscope, surgeons rely on navigation
      systems to guide them within the nasal cavity. State of the art navigation
      systems report registration accuracy of over 1mm, which is large compared to the
      size of the nasal airways. We present an anatomically constrained video-CT
      registration algorithm that incorporates multiple video features. Our algorithm
      is robust in the presence of outliers. We also test our algorithm on simulated
      and in-vivo data, and test its accuracy against degrading initializations.

PMID- 29226286
TI  - Hydrothermal encapsulation of VO2(A) nanorods in amorphous carbon by
      carbonization of glucose for energy storage devices.
AB  - In recent decades, tremendous attention has been paid to the development of new
      electrode materials with high capacitance to meet the requirements of electrode
      materials in supercapacitors. Among vanadium oxides, VO2(A) has recently received
      increasing attention due to its unique layered structure, phase transformation
      and applications in Li-ion batteries. However, few studies have focused on the
      electrochemical properties of VO2(A) as electrochemical capacitors. Herein, we
      develop a facile hydrothermal method to prepare VO2(A)@C core-shell structured
      composites by carbonization of glucose in the presence of V2O5 nanowires. The
      electrochemical properties of the VO2(A)@C core-shell composites are investigated
      as a supercapacitor electrode material for the first time; the composites show
      excellent pseudocapacitive behavior and display a specific capacitance as high as
      179 F g-1 at 1 A g-1. A flexible asymmetric supercapacitor device is fabricated
      using VO2(A)@C composites and activated carbon and delivers an excellent
      capacitance of 0.5 F cm-2 at a scan rate of 5 mV s-1. Replacing the aqueous
      electrolyte with a LiCl/PVA gel electrolyte can efficiently improve the cycling
      performance to 85% retention after 1600 cycles. The good electrochemical
      performance of the composites indicates their high potential as electrode
      materials for supercapacitors.

PMID- 29226288
TI  - Exploration of new water stable proton-conducting materials in an amino acid
      templated metal phosphate system.
AB  - Two new metal phosphates, namely, Zn(HPO4)(dl-C3H7NO2) (SCU-4) and
      In(HPO4)(H2PO4)(dl-C3H7NO2) (SCU-12), were prepared in the presence of the amino
      acid l-alanine. SCU-4 has a ladderlike structure with edge-sharing 4-rings. SCU
      12 represents the first example of a three-dimensional metal phosphate templated
      by an amino acid. It remains stable in boiling water and shows a high proton
      conductivity at room temperature under 98% relative humidity.

PMID- 29226289
TI  - Ionophore-based optical nanosensors incorporating hydrophobic carbon dots and a
      pH-sensitive quencher dye for sodium detection.
AB  - Nanosensors present a biological monitoring method that is biocompatible,
      reversible, and nano-scale, and they offer many advantages over traditional
      organic indicators. Typical ionophore-based nanosensors incorporate nile-blue
      derivative pH indicators but suffer from photobleaching while quantum dot
      alternatives pose a potential toxicity risk. In order to address this challenge,
      sodium selective nanosensors containing carbon dots and a pH-sensitive quencher
      molecule were developed based on an ion-exchange theory and a decoupled
      recognition element from the pH indicator. Carbon dots were synthesized and
      integrated into nanosensors containing a pH-indicator, an analyte-binding ligand
      (ionophore), and a charge-balancing additive. These nanosensors are ion-selective
      against potassium (selectivity coefficient of 0.4) and lithium (selectivity
      coefficient of 0.9). Reversible nanosensor response to sodium is also
      demonstrated. The carbon dot nanosensors are resistant to changes in optical
      properties for at least 12 h and display stable selectivity to physiologically
      relevant sodium (alpha = 0.5 of 200 mM NaCl) for a minimum of 6 days.

PMID- 29226290
TI  - Correlating geminal 2JSi-O-Si couplings to structure in framework silicates.
AB  - The dependence of a 29Si geminal J coupling across the inter-tetrahedral linkage
      on local structure was examined using first-principles DFT calculations. The two
      main influences on 2JSi-O-Si were found to be a primary dependence on the linkage
      Si-O-Si angle and a secondary dependence on mean Si-O-Si linkage of the two
      coupled 29Si nuclei. An analytical expression describing these dependences was
      proposed and used to develop an approach for relating the correlated pair of 2JSi
      O-Si coupling and mean 29Si isotropic chemical shift to the linkage Si-O-Si angle
      and the mean Si-O-Si angle of the two coupled 29Si nuclei. An example of this
      analysis is given using 29Si NMR results from the siliceous zeolite Sigma-2.

PMID- 29226291
TI  - Attractive non-DLVO forces induced by adsorption of monovalent organic ions.
AB  - Direct force measurements between negatively charged colloidal particles were
      carried out using an atomic force microscope (AFM) in aqueous solutions
      containing monovalent organic cations, namely tetraphenylarsonium (Ph4As+), 1
      hexyl-3-methylimidazolium (HMIM+), and 1-octyl-3-methylimidazolium (OMIM+). These
      ions adsorb to the particle surface, and induce a charge reversal. The forces
      become attractive at the charge neutralization point, but they are stronger than
      van der Waals forces. This additional and unexpected attraction decays
      exponentially with a decay length of a few nanometers, and is strikingly similar
      to the one previously observed in the presence of multivalent ions. This
      attractive force probably originates from coupled spontaneous charge fluctuations
      on the respective surfaces as initially suggested by Kirkwood and Shumaker.

PMID- 29226292
TI  - Self-assembled uracil complexes containing tautomeric uracils: an IRMPD
      spectroscopic and computation study of the structures of gaseous uracilnCa2+ (n =
      4, 5, or 6) complexes.
AB  - The structures of doubly-charged uracil (U) complexes with Ca2+, UnCa2+ (n = 4,
      5, 6), were studied by infrared multiple photon dissociation (IRMPD) spectroscopy
      and computational methods. The ions were produced by electrospray ionization
      (ESI) and were isolated in the gas phase in a Fourier-transform ion cyclotron
      resonance mass spectrometer (FT-ICR-MS). The recorded IRMPD spectra in both the
      fingerprint and the C-H/N-H/O-H stretching regions, combined with computed
      vibrational spectra, reveal that the structures present in the greatest abundance
      consist of both canonical uracil as well as the lactam (or colloquially "enol")
      tautomer of uracil. U4Ca2+ consists of two hydrogen-bonded dimers of uracil, one
      canonical and one tautomer, with each uracil interacting with Ca2+ through a
      carbonyl oxygen. The structures most consistent with the vibrational spectrum of
      U6Ca2+ consist of two hydrogen-bonded uracil trimers, each composed of two
      canonical and one enolic uracil, with each uracil also interacting with Ca2+
      through carbonyl oxygen. U5Ca2+ consists of one of the aforementioned trimers and
      dimers, each containing one enol tautomerized uracil. The computed structures
      whose vibrational spectra best agree with the experimental vibrational spectra
      are also the lowest-energy structures for all three complexes. This study clearly
      shows that some uracils adopt the normally very high energy enol tautomer in the
      lowest energy gas phase complexes of uracil with a doubly-charged ion like Ca2+.

PMID- 29226293
TI  - Ligand-induced action of the W2866.48 rotamer toggle switch in the beta2
      adrenergic receptor.
AB  - Studies focused on GPCRs, particularly on the beta2-adrenergic receptor (beta2
      AR), have demonstrated the relationship between ligand structure, receptor
      conformational changes and the corresponding pharmacological outcomes. Herein, we
      studied the molecular details of the rotameric flip of the W2866.48 sidechain,
      i.e. a presumed action switch that has not been reported in native beta2-AR thus
      far. It is believed that although both the 'active' and 'inactive' conformers of
      beta2-AR exhibit similar conformations of this switch, it may still play a
      substantial role in the ligand-induced activation of the receptor. By using both
      experimental methods (time-resolved fluorescence spectroscopy) and molecular
      modeling techniques (enhanced-sampling molecular dynamics), we characterized the
      conformational rearrangements of W2866.48 in relation to the type of ligand
      present in the binding cavity and to the conformation of the receptor ('active'
      vs. 'inactive' beta2-AR). We found that the conformational behaviour of W2866.48
      is correlated with the pharmacological character of the ligand present in the
      binding cavity but not with the instantaneous conformation of the receptor.
      Namely, agonists promote the W2866.48 conformations that facilitate the increase
      of the solvation within the inner receptor channel. In contrast, antagonists and
      inverse agonists act toward the decrease of the solvation in the inner channel.
      This creates an opportunity for using computational methodologies in determining
      the pharmacological properties of various ligands. The combination of the time
      resolved fluorescence spectroscopy technique with the enhanced-sampling molecular
      dynamics simulations is shown to be a powerful tool for studying the ligand
      induced conformational rearrangements in GPCRs.

PMID- 29226294
TI  - Kinase-loaded magnetic beads for sequential in vitro phosphorylation of peptides
      and proteins.
AB  - Post-translational modifications, including phosphorylation, greatly impact the
      physiological function of proteins, especially those that are natively unfolded
      and implicated in many neurodegenerative diseases. However, structural and
      functional studies of such proteins require fully defined phosphorylation,
      including those that are not physiological. Thus, the kinases ERK2 and GSK-3beta
      were immobilized to various superparamagnetic beads with carboxylic, aldehyde,
      Ni2+, or Co3+ functional groups, with a view to efficiently phosphorylate
      peptides and proteins in vitro. Full phosphorylation of specific synthetic
      peptides confirmed that beads were successfully loaded with kinases. Remarkably,
      enzymes covalently immobilized on carboxylated SeraMag beads remained active upon
      reuse, with residual activity after 10 uses 99.5 +/- 0.34% for GSK-3beta and 36.2
      +/- 2.01% for ERK2. The beads were also used to sequentially phosphorylate
      recombinant tau, which in vivo is a biomarker of Alzheimer's disease. Thus, a
      system consisting of two fully active kinases immobilized to magnetic beads is
      demonstrated for the first time. In comparison to soluble enzymes, the beads are
      easier to handle, reusable, and thus low-cost. Importantly, these beads are also
      convenient to remove from reactions to minimize contamination of phosphorylated
      products or to exchange with other kinases.

PMID- 29226295
TI  - "Bleaching" glycerol in a microfluidic fuel cell to produce high power density at
      minimal cost.
AB  - Glycerol/bleach flow-through microfluidic fuel cells are presented. Carbon paper
      modified Pt/C nanoparticles were used as the anode and cathode. Glycerol
      oxidation in alkaline medium was tested against hypochlorite reduction in
      alkaline and acidic media. The mixed media system displayed a power density of
      315 mW cm-2 and an open circuit voltage of 1.9-2.0 V.

PMID- 29226296
TI  - Rare-earth metal-mediated PhC[triple bond, length as m-dash]N insertion into N,N
      bis(trimethylsilyl)naphthalene-1,8-diamido dianion - a synthetic approach to
      complexes coordinated by ansa-bridged amido-amidinato ligand.
AB  - Lithium silylamides 1,8-C10H6[N(SiMe3)Li(L)]2 (L = Et2O (); L = TMEDA (1TMEDA)),
      when treated with PhC[triple bond, length as m-dash]N, formed the adducts 1,8
      C10H6[N(SiMe3)Li(N[triple bond, length as m-dash]CPh)(OEt2)][N(SiMe3)Li(OEt2)] ()
      and 1,8-C10H6[N(SiMe3)Li(N[triple bond, length as m-dash]CPh)][N(SiMe3)Li(TMEDA)]
      (2TMEDA) containing one benzonitrile molecule coordinated to Li ion while the
      second molecule retains a coordinated L ligand. The salt metathesis reactions of
      LnCl3 (Ln = Y, Sm) with equimolar amounts of and 2TMEDA (THF, 4 h, 40  degrees C)
      resulted in benzonitrile insertion and formation of new dianionic amido-amidinate
      ligands. The reactions of with LnCl3 afforded ionic chloro complexes [{1,8
      C10H6[NSiMe3][NC(Ph)NSiMe3]}{1,8-C10H6[N(H)SiMe3][NC(Ph)NSiMe3]}LnCl][Li(L)n] (Ln
      = Y, L = THF, n = 4 (3Y), Ln = Sm, L = DME, n = 3 (3Sm)), while the reaction of
      2TMEDA and YCl3 leds to the formation of the neutral salt-free yttrium chloro
      complex {1,8-C10H6[NSiMe3][NC(Ph)NSiMe3]}YCl(TMEDA) (4). The treatment of 3Y and
      4 with tBuOK enabled the synthesis of tert-butoxides [{1,8
      C10H6[NSiMe3][NC(Ph)NSiMe3]}{1,8-C10H6[N(H)SiMe3][NC(Ph)NSiMe3]}YOtBu][Li(THF)4]
      (7) and {1,8-C10H6[NSiMe3][NC(Ph)NSiMe3]}YOtBu(TMEDA) (8). Complexes 7 and 8 were
      evaluated as initiators for the ring opening polymerization of rac-lactide.
      Neutral tert-butoxide complex 8 demonstrated significantly higher activity
      compared to that of ionic 7.

PMID- 29226297
TI  - Pathway-engineering for highly-aligned block copolymer arrays.
AB  - While the ultimate driving force in self-assembly is energy minimization and the
      corresponding evolution towards equilibrium, kinetic effects can also play a very
      strong role. These kinetic effects, such as trapping in metastable states, slow
      coarsening kinetics, and pathway-dependent assembly, are often viewed as
      complications to be overcome. Here, we instead exploit these effects to engineer
      a desired final nano-structure in a block copolymer thin film, by selecting a
      particular ordering pathway through the self-assembly energy landscape. In
      particular, we combine photothermal shearing with high-temperature annealing to
      yield hexagonal arrays of block copolymer cylinders that are aligned in a single
      prescribed direction over macroscopic sample dimensions. Photothermal shearing is
      first used to generate a highly-aligned horizontal cylinder state, with
      subsequent thermal processing used to reorient the morphology to the vertical
      cylinder state in a templated manner. Finally, we demonstrate the successful
      transfer of engineered morphologies into inorganic replicas.

PMID- 29226298
TI  - Water, rest, shade: Can simple actions stop an epidemic of chronic kidney disease
      of unknown etiology among farm workers in Central America?

PMID- 29226299
TI  - Correction to: Diffusion, outcomes and implementation of minimally invasive liver
      surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver
      Surgery) Registry.
AB  - A technical error led to incorrect rendering of the author group in this article.
      The correct authorship is as follows.

PMID- 29226300
TI  - A novel method for treatment of Class III malocclusion in growing patients.
AB  - BACKGROUND: Management of Class III malocclusion is one of the most challenging
      treatments in orthodontics, and several methods have been advocated for treatment
      of this condition. A new treatment protocol involves the use of an alternating
      rapid maxillary expansion and constriction (Alt-RAMEC) protocol, in conjunction
      with full-time Class III elastic wear and coupled with the use of temporary
      anchorage devices (TADs). The aim of this study was to evaluate the dento
      skeletal and profile soft tissue effects of this novel protocol in growing
      participants with retrognathic maxilla. METHODS: Fourteen growing participants (7
      males and 7 females; 12.05 +/- 1.09 years), who displayed Class III malocclusions
      with retrognathic maxilla, were recruited. Pre-treatment records were taken
      before commencing treatment (T1). All participants had a hybrid mini-implant
      supported rapid maxillary expansion (MARME) appliance that was activated by the
      Alt-RAMEC protocol for 9 weeks. Full-time bone-anchored Class III elastics,
      delivering 400 g/side, were then used for maxillary protraction. When positive
      overjet was achieved, protraction was ceased and post-treatment records were
      taken (T2). Linear and angular cephalometric variables were blindly measured by
      one investigator and repeated after 1 month. An error measurement (Dahlberg's
      formula) study was performed to evaluate the intra-examiner reliability. A paired
      sample t test (p < 0.05) was used to compare each variable from T1 to T2.
      RESULTS: Treatment objectives were achieved in all participants within 8.5 weeks
      of protraction. The maxilla significantly protracted (SNA 1.87 degrees +/- 1.06
      degrees ; Vert.T-A 3.29+/- 1.54 mm p < 0.001), while the mandibular base
      significantly redirected posteriorly (SNB -2.03 degrees  +/- 0.85 degrees ,
      Vert.T-B - 3.43+/- 4.47 mm, p < 0.001 and p < 0.05 respectively), resulting in a
      significant improvement in the jaw relationship (ANB 3.95 degrees +/- 0.57
      degrees , p < 0.001; Wits 5.15+/- 1.51 mm, p < 0.001). The Y-axis angle increased
      significantly (1.95 degrees  +/- 1.11 degrees , p < 0.001). The upper incisors
      were significantly proclined (+ 2.98 degrees +/- 2.71 degrees , p < 0.01),
      coupled with a significant retroclination of the lower incisors (- 3.2 degrees +/
      3.4 degrees , p < 0.05). The combined skeletal and dental effects significantly
      improved the overjet (5.62+/- 1.36 mm, p < 0.001) and the soft tissue Harmony
      angle (2.75 degrees  +/- 1.8 degrees , p < 0.001). CONCLUSIONS: Class III
      elastics, combined with the Alt-RAMEC activation protocol of the MARPE appliance,
      is an efficient treatment method for mild/moderate Class III malocclusions. The
      long-term stability of these changes needs further evaluation.

PMID- 29226301
TI  - The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies.
AB  - Since the 1990s, the International Union of Immunological Societies (IUIS) PID
      expert committee (EC), now called Inborn Errors of Immunity Committee, has
      published every other year a classification of the inborn errors of immunity.
      This complete catalog serves as a reference for immunologists and researchers
      worldwide. However, it was unadapted for clinicians at the bedside. For those,
      the IUIS PID EC is now publishing a phenotypical classification since 2013, which
      proved to be more user-friendly. There are now 320 single-gene inborn errors of
      immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto
      immunity, and auto-inflammation. We herein propose the revised 2017 phenotypic
      classification, based on the accompanying 2017 IUIS Inborn Errors of Immunity
      Committee classification.

PMID- 29226303
TI  - Pediatric Development of Molecularly Targeted Oncology Drugs.
AB  - Oncology products developed for adult cancers often receive full waivers of
      pediatric studies. This analysis retrospectively identified products with
      potential pediatric development opportunities despite a full waiver. Initial
      pediatric study plans submitted to the US Food and Drug Administration from 2012
      to 2016 for oncology products with plans to request full waivers of pediatric
      studies were reviewed to determine if a scientific rationale existed for
      pediatric evaluation based on the molecular mechanism of action (MOA), clinical
      experience, nonclinical evidence, or published genome sequencing data. Of the 98
      oncology products reviewed, pediatric studies were eventually conducted in 55
      (56%) despite having a waiver, 33 additional (34%) products were considered to
      have a rationale for pediatric evaluation but were not studied, and 10 (10%)
      products had no current evidence to support pediatric development. Conducting
      pediatric studies based on molecular MOA, rather than indication, provides
      opportunities to evaluate products earlier and accelerate pediatric oncology drug
      development.

PMID- 29226302
TI  - International Union of Immunological Societies: 2017 Primary Immunodeficiency
      Diseases Committee Report on Inborn Errors of Immunity.
AB  - Beginning in 1970, a committee was constituted under the auspices of the World
      Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years
      later, the International Union of Immunological Societies (IUIS) took the remit
      of this committee. The current report details the categorization and listing of
      354 (as of February 2017) inborn errors of immunity. The growth and increasing
      complexity of the field have been impressive, encompassing an increasing variety
      of conditions, and the classification described here will serve as a critical
      reference for immunologists and researchers worldwide.

PMID- 29226304
TI  - Successful medical management of pseudomembranous cystitis in three cats with
      lower urinary tract obstruction.
AB  - CASE REPORT: The present case series describes the clinical course and outcome of
      three cats diagnosed with pseudomembranous cystitis. This is an uncommon
      presentation of lower urinary tract obstruction but can be easily be identified
      by ultrasonography, revealing severe bladder wall thickening and thin hyperechoic
      luminal strips. The condition can be secondary to severe bacterial urinary tract
      infection. All cats were successfully treated with medical management only,
      mainly based on antimicrobials and individualised supportive therapy. CONCLUSION:
      Further evaluation of this condition is necessary in order to determine potential
      underlying aetiologies, pathophysiological mechanisms and the most appropriate
      standardised treatment.

PMID- 29226305
TI  - Association between scalp and intracerebral electroencephalographic seizure-onset
      patterns: A study in different lesional pathological substrates.
AB  - OBJECTIVE: Our purpose was to determine the correlation between scalp
      electroencephalography (EEG) and intracerebral EEG (iEEG) seizure-onset patterns
      in patients with focal lesional epilepsy to determine whether scalp seizure-onset
      patterns can be specific to intracerebral seizure-onset patterns and to lesion
      type. METHODS: We retrospectively analyzed 61 patients with focal epilepsy and a
      structural magnetic resonance imaging (MRI)-visible lesion, who first underwent
      extensive scalp recordings and then iEEG studies (stereo-EEG) for presurgical
      evaluation, and who showed an iEEG seizure onset in the lesional/perilesional
      area. Five seizure-onset patterns were recognized on scalp EEG, and 7 on iEEG,
      and in each patient, only the predominant scalp and iEEG seizure-onset patterns
      were compared. Because scalp and iEEG recordings were acquired at different
      times, we followed strict criteria based on semiology and topography to match
      scalp with intracerebral seizures. RESULTS: Seventy-one pairs of seizure-onset
      patterns matched between scalp and iEEG were identified. Each scalp pattern did
      not correspond to a single intracerebral pattern, but there were significant
      associations: (1) paroxysmal fast activity (>=13 Hz) at scalp onset was
      associated with low-voltage fast activity at iEEG onset (P < .001), with
      malformations of cortical development (P < .001), and with superficial seizure
      onset zone based on iEEG (P < .001); (2) rhythmic slow activity (<13 Hz) at scalp
      onset was associated with low-frequency high-amplitude periodic spikes at iEEG
      onset (P = .0014), with medial temporal atrophy/sclerosis (P < .001), and with
      deep seizure-onset zone (P < .001); and (3) repetitive epileptiform discharge at
      scalp onset was associated with a burst of high-amplitude polyspikes at iEEG
      onset (P = .0002). SIGNIFICANCE: Our results disclosed that in focal epilepsy
      patients with seizures generated in an MRI-visible lesion, some scalp seizure
      onset patterns are highly associated with a specific intracerebral pattern, with
      specific pathologies, and with the depth of seizure-onset zone. These findings
      allow the interpretation of scalp seizure-onset patterns to be significantly more
      informative.

PMID- 29226306
TI  - Symbioses with nitrogen-fixing bacteria: nodulation and phylogenetic data across
      legume genera.
AB  - How species interactions shape global biodiversity and influence diversification
      is a central - but also data-hungry - question in evolutionary ecology.
      Microbially based mutualisms are widespread and could cause diversification by
      ameliorating stress and thus allowing organisms to colonize and adapt to
      otherwise unsuitable habitats. Yet the role of these interactions in generating
      species diversity has received limited attention, especially across large
      taxonomic groups. In the massive angiosperm family Leguminosae, plants often
      associate with root-nodulating bacteria that ameliorate nutrient stress by fixing
      atmospheric nitrogen. These symbioses are ecologically-important interactions,
      influencing community assembly, diversity, and succession, contributing ~100-290
      million tons of N annually to natural ecosystems, and enhancing growth of
      agronomically-important forage and crop plants worldwide. In recent work
      attempting to determine whether mutualism with N-fixing bacteria led to increased
      diversification across legumes, we were unable to definitively resolve the
      relationship between diversification and nodulation. We did, however, succeed in
      compiling a very large searchable, analysis-ready database of nodulation data for
      749 legume genera (98% of Leguminosae genera; LPWG 2017), which, along with
      associated phylogenetic information, will provide a valuable resource for future
      work addressing this question and others. For each legume genus, we provide
      information about the species richness, frequency of nodulation, subfamily
      association, and topological correspondence with an additional data set of 100
      phylogenetic trees curated for database compatibility. We found 386 legume genera
      were confirmed nodulators (i.e., all species examined for nodulation nodulated),
      116 were non-nodulating, four were variable (i.e., containing both confirmed
      nodulators and confirmed non-nodulators), and 243 had not been examined for
      nodulation in published studies. Interestingly, data exploration revealed that
      nodulating legume genera are ~3 * more species-rich than non-nodulating genera,
      but we did not find evidence that this difference in diversity was due to
      differences in net diversification rate. Our metadata file describes in more
      detail the structure of these data that provide a foundational resource for
      future work as more nodulation data become available, and as greater phylogenetic
      resolution of this ca. 19,500-species family comes into focus. We release this
      data set under the Creative Commons 4.0 Attribution-ShareAlike License
      (https://creativecommons.org/licenses/by-sa/4.0/). The data may be used,
      distributed, and reproduced with proper citation of this article.

PMID- 29226307
TI  - Macrolides for treatment of Haemophilus ducreyi infection in sexually active
      adults.
AB  - BACKGROUND: Chancroid is a genital ulcerative disease caused by Haemophilus
      ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of
      genital ulcers. Macrolides may be an effective alternative to treat chancroid
      and, based on their oral administration and duration of therapy, could be
      considered as first line therapy. OBJECTIVES: To assess the effectiveness and
      safety of macrolides for treatment of H ducreyi infection in sexually active
      adults. SEARCH METHODS: We searched the Cochrane STI Group Specialized Register,
      CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of
      Science to 30 October 2017. We also handsearched conference proceedings and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled
      trials (RCTs) comparing macrolides in different regimens or with other
      therapeutic alternatives for chancroid. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trials for inclusion, extracted data and assessed
      risk of bias. We resolved disagreements through consensus. We used the GRADE
      approach to assess the quality of the evidence. MAIN RESULTS: Seven RCTs (875
      participants) met our inclusion criteria, of which four were funded by industry.
      Five studies (664 participants) compared macrolides with ceftriaxone,
      ciprofloxacin, spectinomycin or thiamphenicol. Low quality evidence suggested
      there was no difference between the groups after treatment in terms of clinical
      cure (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.21; 2 studies,
      340 participants with syndromic approach and RR 1.06, 95% CI 0.98 to 1.15; 5
      studies, 348 participants with aetiological diagnosis) or improvement (RR 0.89,
      95% CI 0.52 to 1.52; 2 studies, 340 participants with syndromic approach and RR
      0.80, 95% CI 0.42 to 1.51; 3 studies, 187 participants with aetiological
      diagnosis). Based on low and very low quality evidence, there was no difference
      between macrolides and any other antibiotic treatments for microbiological cure
      (RR 0.93, 95% CI 0.74 to 1.16; 1 study, 45 participants) and minor adverse
      effects (RR 1.34, 95% CI 0.24 to 7.51; 3 studies, 412 participants).Two trials
      (269 participants) compared erythromycin with any other macrolide type. Low
      quality evidence suggested that, compared with azithromycin or rosaramicin, long
      courses of erythromycin did not increase clinical cure (RR 1.00, 95% CI 0.91 to
      1.10; 2 studies, 269 participants with syndromic approach and RR 1.04, 95% CI
      0.93 to 1.16; 2 studies, 211 participants with aetiological diagnosis), with a
      similar frequency of minor adverse effects between the groups (RR 1.14, 95% CI
      0.63 to 2.06; 1 trial, 101 participants). For this comparison, subgroup analysis
      found no difference between HIV-positive participants (RR 1.02, 95% CI 0.73 to
      1.43; 1 study, 38 participants) and HIV-negative participants (RR 1.04, 95% CI
      0.94 to 1.14; 1 study, 89 participants). We downgraded the quality of evidence to
      low, because of imprecision, some limitations on risk of bias and
      heterogeneity.None of the trials reported serious adverse events, cost
      effectiveness and participant satisfaction. AUTHORS' CONCLUSIONS: At present, the
      quality of the evidence on the effectiveness and safety of macrolides for
      treatment of H ducreyi infection in sexually active adults is low, implying that
      we are uncertain about the estimated treatment effect. There is no statistically
      significant difference between the available therapeutic alternatives for the
      treatment of sexually active adults with genital ulcers compatible with
      chancroid. Low quality evidence suggests that azithromycin could be considered as
      the first therapeutic alternative, based on their mono-dose oral administration,
      with a similar safety and effectiveness profile, when it is compared with long
      term erythromycin use.Due to sparse available evidence about the safety and
      effectiveness of macrolides to treat H ducreyi infection in people with HIV,
      these results should be taken with caution.

PMID- 29226308
TI  - HLA-B*1502 haplotype screening prior to carbamazepine administration in
      individuals of south-east Asian ancestry nears cost-effectiveness in preventing
      severe cutaneous adverse drug reactions.

PMID- 29226309
TI  - Medical Malpractice Liability Exposure and OB/GYN Physician Delivery Decisions.
AB  - OBJECTIVE: This study examines the effect of physician medical malpractice
      liability exposure on primary Cesarean and vaginal births after Cesarean (VBACs).
      DATA SOURCES/STUDY SETTING: Secondary data on hospital births from Florida
      Hospital Inpatient File, physician characteristics from American Medical
      Association Physician Masterfile, and physician malpractice claim history from
      Florida Office of Insurance Regulation. STUDY DESIGN: Our study estimates the
      effects of physician malpractice liability exposure on Cesareans and VBACs using
      panel data and a multivariate, fixed effects model. DATA COLLECTION: We merge
      three secondary data sources based on unique physician license numbers between
      1994 and 2010. PRINCIPAL FINDINGS: We find no evidence that the first malpractice
      claim affects primary Cesarean deliveries. We find, however, that the first
      malpractice claim decreases the likelihood of a VBAC (conditional on a prior
      Cesarean delivery) by 1.2-1.9 percentage points (approximately 10 percent
      relative to mean VBAC incidence). This finding is robust to focusing on
      obstetrics-related malpractice claims, as well as to considering different
      malpractice claims (first report, first severe report, and first lawsuit).
      CONCLUSIONS: Given the increase in both primary and repeat Cesarean deliveries,
      our results suggest that physician malpractice liability exposure is responsible
      for a relatively small share of the VBAC decrease.

PMID- 29226311
TI  - Emerging Innovative Therapeutic Approaches Leveraging Cyclin-Dependent Kinase
      Inhibitors to Treat Advanced Breast Cancer.
AB  - Estrogen receptor-positive (ER+) tumors represent the most common form of breast
      cancer. Although endocrine therapy (ET) results in benefit for the majority of
      these patients, disease progression invariably occurs. The discovery of the
      relation between cyclin-dependent kinases (CDKs) and the ER pathways is one of
      the major advances in unveiling mechanisms of resistance to ET. In this article
      we review the role of CDK4/6 inhibitors in ER + breast cancer patients.

PMID- 29226310
TI  - Long-term behavioural outcomes after paediatric convulsive status epilepticus: a
      population-based cohort study.
AB  - AIM: To describe behavioural and psychiatric outcomes of children within 10 years
      of convulsive status epilepticus (CSE). METHOD: Children originally identified by
      the population-based North London Convulsive Status Epilepticus in Childhood
      Surveillance Study were followed-up between July 2009 and February 2013. They
      were grouped into epilepsy- and non-epilepsy-related CSE, and compared with
      population norms and healthy controls using the Strengths and Difficulties
      Questionnaire; the Autism Spectrum Screening Questionnaire; and the Swanson,
      Nolan, and Pelham questionnaire. Children who scored above recommended clinical
      cut-offs on any scale were invited for a neuropsychiatric assessment. Regression
      models were fitted to identify clinically relevant covariates associated with
      behavioural outcomes. RESULTS: At a mean follow-up of 8.1 years post-CSE, 28% of
      enrolled children were found to have a psychiatric disorder. Children with
      epilepsy-related CSE scored higher than norms on all scales and children with non
      epilepsy-related CSE scored higher than norms on the Strengths and Difficulties
      Questionnaire and the Autism Spectrum Screening Questionnaire. Presence of
      seizures at baseline and recurrence of CSE was associated with worse outcomes in
      the group with epilepsy. Intellectual abilities were associated with behavioural
      outcomes in all participants. INTERPRETATION: A large proportion of children
      manifest behavioural issues 8 years after CSE. The present data highlight the
      need for behavioural screening in children with neurodevelopmental impairments
      post-CSE. WHAT THIS PAPER ADDS: Eight years post convulsive status epilepticus
      (CSE), 37% of parents report behavioural issues. Of enrolled children, 28% were
      found to have a Diagnostic and Statistical Manual mental disorder. Intellectual
      abilities are strongly associated with behavioural outcomes in children post-CSE.

PMID- 29226312
TI  - Proportion of melanoma excisions performed by different specialties in Australia.

PMID- 29226313
TI  - Model-Based Assessments of CYP-Mediated Drug-Drug Interaction Risk of Alectinib:
      Physiologically Based Pharmacokinetic Modeling Supported Clinical Development.
AB  - Alectinib is a selective anaplastic lymphoma kinase (ALK) inhibitor approved for
      the treatment of ALK-positive non-small cell lung cancer. Alectinib and its major
      active metabolite M4 exhibited drug-drug interaction (DDI) potential through
      cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8 in vitro. Clinical relevance of
      the DDI risk was investigated as part of a rapid development program to fulfill
      the breakthrough therapy designation. Therefore, a strategy with a combination of
      physiologically based pharmacokinetic (PBPK) modeling and limited clinical trials
      focused on generating informative data for modeling was made to ensure
      extrapolation ability of DDI risk. The PBPK modeling has provided mechanistic
      insight into the low victim DDI risk of alectinib through CYP3A4 by a novel two
      dimensional analysis for fmCYP3A4 and FG , and demonstrated negligible CYPs 2C8
      and 3A4 enzyme-modulating effects at clinically relevant exposure. This work
      supports that alectinib can be prescribed without dose adjustment for CYP
      mediated DDI liabilities.

PMID- 29226314
TI  - Sneezing in Primary Headaches With Cranial Autonomic Symptoms: Pathophysiological
      Considerations. A Series of Case Reports.
AB  - OBJECTIVE: To report a case series of sneezing systematically occurring in two
      cases with migraine and cranial autonomic symptoms and two with cluster headache.
      BACKGROUND: Sneezing occurring systematically during cluster headache or migraine
      is a rare condition. Sneezing has been described as a specific trigger for
      migraine. METHODS: Case reports. CASE SERIES: We describe four patients with
      primary headaches, presenting systematic sneezing at a definite time of
      premonitory, postdromal, or headache phase. All of these headaches were
      associated with cranial autonomic symptoms. CONCLUSION: Sneezing is a symptom
      associated with primary headaches. The definite place of sneezing in these
      patients suggests a particular implication of hypothalamus in the pathophysiology
      of these cases.

PMID- 29226315
TI  - Air exposure may be associated with the histological differentiation of a
      cultured epidermal autograft (JACE).

PMID- 29226316
TI  - Interpersonal predictors of stress generation: Is there a super factor?
AB  - Hammen's (1991, Journal of Abnormal Psychology, 100, 555-561) seminal paper on
      stress generation highlighted the reciprocal relationship between stress and
      depression. Not only does stress predict depression, but women with a diagnosis
      of depression also experienced subsequent increased levels of stress. In the
      ensuing years, depression researchers have moved beyond clinical predictors and
      examined whether depression vulnerability factors also contribute to stress
      generation. This interest has led to a growing focus on interpersonal
      vulnerability factors that contribute to stress generation. To date, the research
      examining interpersonal predictors of stress generation has tended to examine
      vulnerability factors singly and thus potential overlap and unique predictions
      among vulnerability factors have not been determined. This study examines
      interpersonal vulnerability factors from various schools of thought (dependency,
      attachment, and unmitigated communion) as predictors of interpersonal stress
      generation. Three hundred and sixty-four young adults completed baseline measures
      of interpersonal vulnerabilities and provided weekly reports of depressive
      symptoms and stressful life events. Multilevel models were estimated to examine
      their unique predictions of interpersonal stress generation. Despite converging
      theories, there does not appear to be a single super factor. Of the interpersonal
      vulnerability factors tested, anxious attachment emerged as a consistent
      predictor of interpersonal stress generation both when examined singly and when
      in combination with related variables.

PMID- 29226318
TI  - My Mom is Dead (and that is OK).

PMID- 29226317
TI  - Partnerships in European biomolecular research: the EMBL paradigm.

PMID- 29226319
TI  - LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.
AB  - The study was employed to probe long non-coding RNA X-inactive specific
      transcript RNA (lncRNA XIST) expression profile and its influence on cell cycle,
      proliferation and apoptosis in myocardial cells. We also aimed to explore the
      possible meditating relationship between XIST, PDE4D and miR-130a-3p. Gene
      differential analysis was carried out using Human LncRNA Microarray V3.0.
      Quantitative real-time PCR (qRT-PCR) was used to test mRNA expressions of XIST,
      miR-130a-3p and PDE4D in normal cells and post-myocardial infarction (MI) cells.
      Western blot was applied to determine the protein expression profile of PED4D.
      Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after
      silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry,
      respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in
      myocardial cells were verified by dual luciferase reporter assay. Simulated MI
      environment was constructed by performing anoxic preconditioning in normal cells
      to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were
      overexpressed in post-MI myocardial cells, while miR-130a-3p was underexpressed
      in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted
      myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell
      proliferation. XIST down-regulated miR-130a-3p and PDE4D was a direct target of
      miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by
      PDE4D can be reversed by miR-130a-3p. This article is protected by copyright. All
      rights reserved.

PMID- 29226321
TI  - The severity of periodontitis and metabolic syndrome in Korean population: The
      Dong-gu study.
AB  - OBJECTIVES: We assessed the association between periodontal disease status and
      metabolic syndrome (MetS) and its individual components in Korean adults over 50
      years old. MATERIAL AND METHODS: In the Dong-gu study, 5078 men and women aged
      over 50 years were included. They underwent a questionnaire survey, physical
      assessment, biochemical assessment and periodontal assessment. The percentages of
      sites with periodontal probing depth >=4 mm, and clinical attachment loss >=4 mm
      were recorded for each participant. Periodontal disease was also classified by
      the Centers for Disease Control and Prevention/American Academy of Periodontology
      definition of periodontitis and the American Academy of Periodontology definition
      (1999). MetS was defined by the 2009 guidelines of the International Diabetes
      Federation. This study used multivariate negative binominal regression analysis
      to assess the association between the severity of periodontitis and MetS, after
      age, smoking habits, alcohol consumption and physical activity related factors
      were adjusted for. RESULTS: Prevalence of MetS was 32.3%, 36.2% and 45.9% among
      men with no or mild, moderate and severe periodontitis, respectively. The
      severity of periodontitis was positively associated with the prevalent MetS in
      men but not in women. In men, severe periodontitis showed a higher risk of MetS
      than those with no or mild periodontitis (relative risk 1.43, 95% confidence
      interval 1.17-1.73) after adjusting for confounders. Periodontal probing depth
      was positively associated with the prevalence of MetS in both genders. In the
      analysis separated by individual MetS components, periodontitis severity was
      positively associated with hypertriglyceridemia and low high-density lipoprotein
      cholesterol in men, while positively associated with low high-density lipoprotein
      cholesterol and abdominal obesity in women. CONCLUSION: Increasing the severity
      of periodontitis was associated with the risk of prevalent MetS in Korean adults.
      This result confirmed that periodontal inflammation might be a contributive
      factor of MetS.

PMID- 29226320
TI  - Breast cancer-associated mitochondrial DNA haplogroup promotes neoplastic growth
      via ROS-mediated AKT activation.
AB  - In the last decade, mitochondrial DNA (mtDNA) haplogroups have been associated
      with the occurrence of breast cancer. However, the underlying mechanism is not
      known. Combining a case-control study with a large cohort of women from Southern
      China with breast cancer and functional analyses with trans-mitochondrial
      technology, we demonstrate that the D5 haplogroup is associated with an increased
      risk of breast cancer [odds ratio (OR) = 2.789; 95% confidence interval (CI)
      [1.318, 5.901]; p = 0.007]. Furthermore, mitochondrial respiration, mitochondrial
      ATP content and membrane potential, were lower in both bone osteosarcoma and
      breast cancer cell models of cytoplasmic hybrids (cybrids) containing the mtDNA
      D5 haplogroup than in those with non-D5 haplogroups. Using in vitro and in vivo
      tumorigenicity assays, we found that cells with the D5 haplogroup were more
      susceptible to tumorigenesis compared to cells with non-D5 haplogroups.
      Mechanistically, the D5 haplogroup may promote tumorigenesis at least partially
      through activation of the v-AKT murine thymoma viral oncogene (AKT) via
      phosphorylation of threonine 308, which is mediated by increased reactive oxygen
      species generation in D5 cybrids. Our findings demonstrate that there is
      decreased mitochondrial function in cells with the D5 haplogroup compared to
      cells with non-D5 haplogroups, which may be associated with increased neoplastic
      growth in breast cancer.

PMID- 29226322
TI  - MiR-1290 promotes proliferation, migration, and invasion of glioma cells by
      targeting LHX6.
AB  - To investigate the interaction of miR-1290 and LHX6 in gliomas, and their
      influence on the propagation and metastasis of glioma cells. The differential
      expression of miR-1290 in glioma cells was identified by chip screening. The
      expression level of miR-1290 and LHX6 were determined by qRT-PCR and Western
      blot. The influence of miR-1290 on propagation of glioma cells were analyzed by
      MTT assay, EdU incorporation, and colony formation, while the impact of miR-1290
      on metastasis was assessed by transwell assay. The relationship between LHX6 and
      miR-1290 was testified by luciferase reporter assay. The gliomas orthotopic
      implantation model of nude mice was established to investigate the influence of
      miR-1290 and LHX6 on tumor growth. Tumor volumes were evaluated by photon
      density, and the expression of Ki67 protein was analyzed by immunohistochemistry.
      MiR-1290 presented a higher expression in glioma cells and tissues. MiR-1290
      overexpression significantly promoted propagation and metastasis of glioma cells,
      while miR-1290 knockdown inhibited glioma development. MiR-1290 suppressed LHX6
      expression, facilitating development of glioma cells. The orthotopic implantation
      model showed that miR-1290 overexpression promoted tumor growth while LHX6
      overexpression inhibited it. MiR-1290 could promote glioma cell propagation and
      metastasis by inhibiting LHX6.

PMID- 29226323
TI  - COPS5 and LASP1 synergistically interact to downregulate 14-3-3sigma expression
      and promote colorectal cancer progression via activating PI3K/AKT pathway.
AB  - Overexpression of LIM and SH3 protein 1 (LASP1) is required for colorectal cancer
      (CRC) development and progression. Here, C-Jun activation domain-binding protein
      1 (Jab1), also known as COP9 signalosome subunit 5 (COPS5), was verified as a new
      LASP1-interacting protein through yeast two-hybrid assay. The role of COPS5 in
      LASP1-mediated CRC progression remains unknown. GST pull-down assay indicated
      that the SH3 domain of LASP1 could directly bind to MPN domain of COPS5. In vitro
      gain- and loss-of-function analyses revealed the stimulatory role of COPS5 on CRC
      cell proliferation, migration and invasion. Endogenous overexpression of COPS5
      could also enhance the homing capacity of CRC cells in vivo. Further analysis
      showed that COPS5 and LASP1 synergistically interact to stimulate the
      ubiquitination and degradation of 14-3-3sigma and promote colorectal cancer
      progression via PI3K/Akt dependent signaling pathway. Clinically, the expression
      of COPS5 was studied in CRC tissues and it is associated with CRC
      differentiation, metastasis and poor prognosis. The colocalization of LASP1 and
      COPS5 was demonstrated in both nonmetastatic and metastatic CRC tissues. A
      positive correlation was found between the expression of LASP1 and COPS5 while a
      negative correlation existed between 14-3-3sigma and COPS5/LASP1 in most CRC
      samples. A combination of COPS5 and LASP1 tends to be an independent prognostic
      indicator for CRC patients, and this is also suitable for CRC without lymph node
      metastasis. The current research has further advanced our understanding on the
      complicated molecular mechanism underlying LASP1-mediated CRC progression, which
      hopefully will contribute to the development of novel diagnostic and therapeutic
      strategies in CRC.

PMID- 29226324
TI  - Tandem walking as a quick screening test for vestibular disorders.
AB  - OBJECTIVES/HYPOTHESIS: Although many screening tests of balance are available,
      few of them have been well validated for clinical or research uses. The goal of
      this study was to test an updated version of an old test, Tandem Walking, to
      determine how useful it is for screening patients with vestibular disorders.
      STUDY DESIGN: Case-control study. METHODS: Subjects were 90 adult patients with
      vestibular disorders and 292 healthy adult controls. They were tested on the
      number of correct tandem steps they could perform with arms crossed and eyes
      closed in a series of 10 steps. Correct steps could be nonconsecutive. Subjects
      were given one practice trial with eyes open and three experimental trials with
      eyes closed. RESULTS: Receiver operating characteristic (ROC), and sensitivity
      and specificity were calculated. ROC values, sensitivity, and specificity were,
      at best, only moderate, no matter how the age range was cut. Even for subjects in
      the age group with the highest ROC value (i.e., age less than 50 years), ROC =
      0.8, sensitivity = 0.77, and specificity = 0.72. CONCLUSIONS: These results
      indicate that 23% of patients will not be identified. Therefore, we recommend
      that if this test is used for screening patients in the clinic or healthy
      volunteers, the result should be interpreted with care. LEVEL OF EVIDENCE: 3b.
      Laryngoscope, 128:1687-1691, 2018.

PMID- 29226325
TI  - LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1
      axis.
AB  - Recent studies have exhibited significant roles of lncRNAs in various tumors'
      development, including colon cancer. Our study focused on the biological roles of
      lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was
      upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and
      HT29 cells compared to the normal human intestinal epithelial HIEC cells.
      Moreover, we observed that miR-129-5p was downregulated in colon cancer cells
      with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit
      the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics
      analysis was used to predict the target microRNA of MALAT1. miR-129-5p was
      identified and confirmed as a direct regulator of MALAT1 and it was shown that
      miR-129-5p mimics were able to restrain the progression of colon cancer cells. In
      addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA
      target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological
      functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing
      MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p
      inhibitors. It was indicated in our investigation that MALAT1 may serve as a
      competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in
      colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1
      axis could be provided as an important prognostic biomarker in colon cancer
      development.

PMID- 29226326
TI  - RETREG1 (FAM134B): A new player in human diseases: 15 years after the discovery
      in cancer.
AB  - FAM134B (family with sequence similarity 134, member B)/RETREG1 and its
      functional roles are relatively new in human diseases. This review aimed to
      summarize various functions of FAM134B since our first discovery of the gene in
      2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates
      turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or
      non-functional expression of FAM134B protein impairs ER-turnover and thereby is
      involved in the pathogenesis of some human diseases. FAM134B inhibition
      contributes to impair proteostasis in the ER due to the accumulation of misfolded
      or aggregated proteins, which in turn leads to compromised neuronal survival and
      progressive neuronal degenerative diseases. Mutations in FAM134B associated with
      hereditary sensory and autonomic neuropathy type IIB (HSAN IIB). Selective
      cleavage of FAM134B by Dengue, Zika, and West Nile virus encoded protease NS2B3
      leads to the increased production of infection units, whereas upregulation of
      FAM134B inhibits viral replication. In cancer, FAM134B acts as a tumor suppressor
      and inhibit cancer growth both in-vitro and in-vivo. Pharmacological upregulation
      of FAM134B resulted in reduced cancer cell growth and proliferation. In addition,
      FAM134B mutations are common in patients with colorectal adenocarcinoma, and
      oesophageal squamous cell carcinoma. These mutations and expression changes of
      FAM134B were associated with the biological aggressiveness of these cancers.
      FAM134B also plays a role in allergic rhinitis, vascular dementia, and
      identification of stem cells. Taken together, information available in the
      literature suggests that FAM134B plays critical roles in human diseases, by
      interacting with different biological and chemical mediators, which are primarily
      regulated by ER turnover.

PMID- 29226327
TI  - Medication use and kidney cancer survival: A population-based study.
AB  - Several studies demonstrate that use of commonly prescribed medications is
      associated with improved survival in various malignancies. Methods of classifying
      medication use in many of these studies, however, do not account for intermittent
      or cumulative use. Moreover, there are limited data in kidney cancer. Therefore,
      we performed a population-based cohort study utilizing healthcare databases in
      Ontario, Canada. We identified patients aged >=65 with an incident diagnosis of
      kidney cancer between 1997 and 2013 and examined use of nine putative anti
      neoplastic medications using prescription claims. Cox proportional hazard models
      evaluated the association of medication exposure on cancer-specific and overall
      survival. We conducted three separate analyses: the effect of cumulative duration
      of exposure to the study medications on outcomes, the effect of current exposure
      (in a binary nature) and the effect of exposure at diagnosis. During the 16-year
      study period, we studied 9,124 patients. Increasing cumulative use of angiotensin
      converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and
      selective serotonin reuptake inhibitors were associated with markedly improved
      cancer-specific survival; increasing use of NSAIDs was associated with markedly
      improved overall survival. These results were generally discordant with analyses
      evaluating the effect of current use and exposure at diagnosis. In conclusion,
      pharmacoepidemiology studies may be sensitive to the method of analysis;
      cumulative use analyses may be the most robust as it accounts for intermittent
      use and supports a dose-outcome relationship. Prospective studies are needed to
      confirm whether patients diagnosed with kidney cancer should be started on an
      angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake
      inhibitor to improve survival.

PMID- 29226328
TI  - Magnetic resonance thoracic ductography assessment of serial changes in the
      thoracic duct after the intake of a fatty meal.
AB  - The thoracic duct, a terminal lymph vessel, is thought to dilate after the intake
      of a fatty meal. However, this physiological change has not been well explored in
      vivo. Therefore, the present study aimed to assess serial changes in the thoracic
      duct after the intake of a fatty meal using magnetic resonance thoracic
      ductography (MRTD). Eight healthy volunteers were subjected to one MRTD scan
      before a fatty meal and eight serial MRTD scans every hour thereafter. The cross
      sectional areas of the thoracic duct were estimated using MRTD measurements of
      the diameters of the thoracic duct at the upper edge of the aortic arch, the
      tracheal bifurcation, the mid-point between the tracheal bifurcation and the left
      part of the diaphragm and the left part of the diaphragm. The change-rates in
      these areas were calculated before and after the fatty meal intake, and the
      maximal change-rate and timing of its achievement were determined for each
      subject. The summed change-rates in the four portions of the thoracic duct ranged
      from -40.1 to 81.3%, with maximal change-rates for each subject ranging from 22.8
      to 81.3% (mean, 50.4%). Although individual variations were observed, most
      subjects (88.9%) exhibited a maximal change-rate at 4-6 h after meal intake, with
      subsequent decreases at 7-8 h. In conclusion, MRTD revealed a tendency toward
      thoracic duct enlargement at 4-6 h after the intake of a fatty meal, followed by
      contraction.

PMID- 29226329
TI  - Expectations and needs of Ugandan women for improved quality of childbirth care
      in health facilities: A qualitative study.
AB  - OBJECTIVE: To describe the experiences, expectations, and needs of urban Ugandan
      women in relation to good-quality facility childbirth. METHODS: Women who had
      given birth in the 12 months prior to the study were purposively sampled and
      interviewed, or included in focus groups. Thematic analysis was used, and the
      data were interpreted within the context of an existing quality of care
      framework. RESULTS: Forty-five in-depth interviews and six focus group
      discussions were conducted. Respect and dignity, timely communication, competent
      skilled staff, and availability of medical supplies were central to women's
      accounts of quality care, or a lack of it. The hope for a live baby motivated
      women to seek facility-based childbirth. They expected to encounter competent,
      respectful, and caring staff with appropriate skills. In some cases, they could
      only fulfill these expectations through additional personal financial payments to
      staff, for clinical supplies, or to guarantee that they would be attended by
      someone with suitable skills. CONCLUSION: Long-term improvement in quality of
      maternity care in Uganda requires enhancement of the interaction between women
      and health staff in facilities, and investment in staff and resources to ensure
      that safe, respectful care is not dependent on willingness and/or capacity to
      pay.

PMID- 29226330
TI  - Transcutaneous immunization with pneumococcal surface protein A in mice.
AB  - OBJECTIVE: Pneumococcal infection caused by Streptococcus pneumoniae is a major
      upper respiratory tract disease that causes severe illness and mortality.
      Therefore, it is important to develop safe and effective vaccines to prevent
      pneumococcal infections. The goal of the study was to investigate the
      effectiveness of transcutaneous immunization (TCI) for induction of pneumococcal
      surface protein A (PspA) responses in the upper respiratory tract. METHODS:
      C57BL/6 mice were transcutaneously immunized with 1 MUg of PspA and 2 MUg of
      cholera toxin (CT) six times at weekly intervals and compared with
      transcutaneously treated controls (PBS alone/PspA alone/CT alone). Two weeks
      after the final immunization, nasal washes (NWs), saliva, and plasma samples were
      collected and subjected to a PspA-specific ELISA. Three weeks after the final
      immunization, mice were challenged with S. pneumoniae strain EF3030, and the
      numbers of CFUs in NWs and nasal passages (NPs) were determined. RESULTS: Higher
      levels of PspA-specific IgM, IgG, and IgA Abs were noted in plasma of TCI with
      PspA plus CT compared with controls. Transcutaneous immunization mice also had
      significantly increased PspA-specific S-IgA Ab responses in NWs and saliva and,
      importantly, showed significantly lower numbers of bacteria CFUs in NWs and NPs
      compared with controls. CONCLUSION: These results show that TCI with PspA plus CT
      induces antigen-specific mucosal and systemic immune responses. This suggests
      that this method is an effective mucosal immunization strategy for induction of
      protective pneumococcal-specific Ab responses in blockade of S. pneumoniae
      colonization of the nasal cavity. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E91
      E96, 2018.

PMID- 29226331
TI  - A novel pathway activated by somatostatin receptor type 2 (SST2): Inhibition of
      pituitary tumor cell migration and invasion through cytoskeleton protein
      recruitment.
AB  - The pharmacological therapy of GH-secreting pituitary tumors is based on
      somatostatin (SS) analogs that reduce GH secretion and cell proliferation by
      binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been
      demonstrated in different cell models, but no data on pituitary tumors are
      available. Aims of our study were to evaluate SST2 effects on migration and
      invasion of human and rat tumoral somatotrophs, and to elucidate the molecular
      mechanism involved focusing on the role of cofilin and filamin A (FLNA). Our data
      revealed that SST2 agonist BIM23120 significantly reduced GH3 cells migration (
      22% +/- 3.6%, p < 0.001) and invasion on collagen IV (-31.3% +/- 12.2%, p <
      0.01), both these effects being reproduced by octreotide and pasireotide. Similar
      results were obtained in primary cultured cells from human GH-secreting tumors.
      These inhibitory actions were accompanied by a marked increase in RhoA/ROCK
      dependent cofilin phosphorylation (about 2.7-fold in GH3 and 2.1-fold in human
      primary cells). Accordingly, the anti-invasive effect of the SS analog was
      mimicked by the overexpression in GH3 cells of the S3D phosphomimetic cofilin
      mutant, and abolished by both phosphodeficient S3A cofilin and a specific ROCK
      inhibitor that prevented cofilin phosphorylation. Moreover, FLNA silencing and
      FLNA dominant-negative mutants FLNA19-20 and FLNA21-24 transfection demonstrated
      that FLNA plays a scaffold function for SST2-mediated cofilin phosphorylation.
      Accordingly, cofilin recruitment to agonist-activated SST2 was completely lost in
      FLNA silenced cells. In conclusion, we demonstrated that SST2 inhibits rat and
      human tumoral somatotrophs migration and invasion through a molecular mechanism
      that involves FLNA-dependent cofilin recruitment and phosphorylation.

PMID- 29226332
TI  - Preoperative prediction nomogram based on primary tumor miRNAs signature and
      clinical-related features for axillary lymph node metastasis in early-stage
      invasive breast cancer.
AB  - More than half patients who undergo axillary lymph node (ALN) surgery are ALN
      negative in early-stage invasive breast cancer (EIBC). Thus, to avoid excessive
      treatment, we aim to establish and validate a novel nomogram model for the
      preoperative diagnosis of ALN status in patients with EIBC. In total, 864
      patients with EIBC from two independent centers were enrolled in our study. For
      the discovery set, miRNAs expression profiling with functional roles in ALN
      metastasis was discovered by microarray analysis and validated by quantitative
      polymerase chain reaction (PCR). For the training and validation cohorts, we used
      PCR to quantify miRNAs expression in a model development cohort and assessed
      miRNAs signature in an internal validation cohort and external independent
      validation cohort. Multivariable logistic regression analyses were used to
      establish a nomogram model for the likelihood of ALN metastasis from miRNAs
      signature and clinical variables. A signature of nine-miRNA was significantly
      associated with ALN status. The predictive ability of our nomogram that included
      miRNAs signature and clinical-related variables (age, tumor size, tumor location
      and axillary ultrasound-reported ALN status) was significantly greater than a
      model that only considered clinical-related factors (concordance index: 0.856,
      0.796) and also performed well in the two validation cohorts (concordance index:
      0.841, 0.747). Our nomogram is a reliable prediction method that can be
      conveniently used to preoperatively predict ALN status in patients with EIBC.
      Therefore, after further confirmation in prospective and multicenter clinical
      trial, omission of axillary surgery may be feasible for some patients with EIBC
      in the future.

PMID- 29226333
TI  - p53 and miR-210 regulated NeuroD2, a neuronal basic helix-loop-helix
      transcription factor, is downregulated in glioblastoma patients and functions as
      a tumor suppressor under hypoxic microenvironment.
AB  - The factors involved in cell differentiation have recently garnered interest for
      their role in inhibition of pathogenesis in various tumors. However, their role
      in glioblastoma (GBM) remains poorly understood. We analyzed The Cancer Genome
      Atlas (TCGA) GBM data and found significant downregulation of neurogenic
      differentiation factor NeuroD2 in GBM patients. Low levels of NeuroD2 were found
      to be correlated with poor overall survival of GBM patients in TCGA dataset as
      well as in our cohort. Interestingly, NeuroD2 was shown to be transcriptionally
      induced by p53 and post-transcriptionally targeted by hypoxia- inducible miRNA,
      miR-210. NeuroD2 overexpression diminished GBM aggressiveness by inhibiting cell
      proliferation, migration and promoting apoptosis under hypoxia. NeuroD2
      overexpressing GBM cells failed to form three-dimensional (3D)-tumor spheroids
      and displayed reduced migration in a 3D gelatin matrix. NeuroD2 gene signature
      was enriched in pathways belonging to cytokine-cytokine receptor interaction, TNF
      signaling, PI3K-AKT signaling, focal adhesion and ECM-receptor interaction.
      Overall, our study identifies a novel role of NeuroD2 as a tumor suppressor and
      prognostic biomarker in GBM the levels of which are tightly regulated by p53 and
      miR-210. Overexpressing NeuroD2 may potentially be a simple and efficient
      therapeutic strategy to inhibit the malignant phenotype of GBM cells.

PMID- 29226334
TI  - Early Stage olfactory neuroblastoma and the impact of resecting dura and
      olfactory bulb.
AB  - OBJECTIVE: Compare outcomes of patients with olfactory neuroblastoma (ONB)
      without skull base involvement treated with and without resection of the dura and
      olfactory bulb. METHODS: Retrospective review of ONB patients treated from 1992
      to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston,
      Texas, U.S.A.). Primary outcomes were overall and disease-free survival. RESULTS:
      Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%),
      Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the
      nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of
      patients. Twenty-five patients (71%) received surgery and radiation, whereas the
      remainder had surgery alone. Five patients (14%) had bony skull base resection,
      and eight patients (23%) had resection of bony skull base, dura, and olfactory
      bulb. Surgical margins were grossly positive in one patient (3%) and
      microscopically positive in four patients (12%). The 5- and 10-year overall
      survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival
      (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was
      associated with better DFS (P = 0.05), but dura and olfactory bulb resection was
      not (P = 0.11). There was a trend toward improved DFS in patients with negative
      resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and
      postoperative radiotherapy did not impact DFS. CONCLUSION: Most Kadish A/B ONB
      tumors have low Hyams grade, unilateral involvement, and favorable survival
      outcomes. Resection of the dura and olfactory bulb is not oncologically
      advantageous in patients without skull base involvement who are surgically
      treated with negative resection margins and cribriform resection. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:1274-1280, 2018.

PMID- 29226335
TI  - Cancer incidence in northern Thailand: Results from six population-based cancer
      registries 1993-2012.
AB  - Rapid changes in social and economic development have led to cancer becoming a
      major cause of national morbidity and mortality in Thailand. Cancer registries
      have been critical in documenting subnational cancer patterns and transitions in
      the country; with the establishment of six registries in northern Thailand, a
      comprehensive assessment of the scale and profile of cancer is now possible in
      the region. Cancers of the liver, lung, colorectum, breast and cervix were the
      major cancers 2008-2012, although variations in the profiles of cancer were
      observed, with a very high incidence of liver cancer seen among males in Phrae,
      corresponding to one in 11 men developing the disease in a lifetime. Based on
      data from Lampang and Chiang Mai 1993-2012, rates of lung and cervical cancer
      incidence have declined, while liver, colorectal and breast cancer incidence have
      been increasing up to 2012. A more detailed investigation of the incidence trends
      for specific cancer sites and subtypes at the local level are crucial to the
      monitoring and evaluation of the cancer control interventions implemented within
      the Thai national cancer control programme (NCCP). Priority should be given to
      extend the capacity of the new registries in northern Thailand, ensuring
      improvement in quality and utilization of the data to drive epidemiologic
      research and cancer control.

PMID- 29226336
TI  - Single-pass incremental force updates for adaptively restrained molecular
      dynamics.
AB  - Adaptively restrained molecular dynamics (ARMD) allows users to perform more
      integration steps in wall-clock time by switching on and off positional degrees
      of freedoms. This article presents new, single-pass incremental force updates
      algorithms to efficiently simulate a system using ARMD. We assessed different
      algorithms for speedup measurements and implemented them in the LAMMPS MD
      package. We validated the single-pass incremental force update algorithm on four
      different benchmarks using diverse pair potentials. The proposed algorithm allows
      us to perform simulation of a system faster than traditional MD in both NVE and
      NVT ensembles. Moreover, ARMD using the new single-pass algorithm speeds up the
      convergence of observables in wall-clock time. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226337
TI  - Designing In and Around Tolerability Considerations for Immunotherapy
      Combinations.
AB  - Over a century ago, paths diverged in the treatment of cancer: the well-traveled
      path employed cytotoxic chemotherapy drugs, while one of the roads less traveled
      included immunotherapies. Cancer immunotherapy is now a path to durable
      responses, however not all patients benefit. Immunotherapy combinations promise
      responses for a larger proportion of patients, but tolerability can prove to be a
      barrier. Providing deep, durable responses to more patients requires us to
      successfully navigate emerging combination tolerability issues.

PMID- 29226338
TI  - Do surfaces of positive electrostatic potential on different halogen derivatives
      in molecules attract? like attracting like!
AB  - Coulomb's law states that like charges repel, and unlike charges attract.
      However, it has recently been theoretically revealed that two similarly charged
      conducting spheres will almost always attract each other when both are in close
      proximity. Using multiscale first principles calculations, we illustrate
      practical examples of several intermolecular complexes that are formed by the
      consequences of attraction between positive atomic sites of similar or dissimilar
      electrostatic surface potential on interacting molecules. The results of the
      quantum theory of atoms in molecules and symmetry adapted perturbation theory
      support the attraction between the positive sites, characterizing the F***X (X =
      F, Cl, Br) intermolecular interactions in a series of 20 binary complexes as
      closed-shell type, although the molecular electrostatic surface potential
      approach does not (a failure!). Dispersion that has an r-6 dependence, where r is
      the equilibrium distance of separation, is found to be the sole driving force
      pushing the two positive sites to attract. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226339
TI  - Development of an artificial neural network model for risk assessment of skin
      sensitization using human cell line activation test, direct peptide reactivity
      assay, KeratinoSensTM and in silico structure alert parameter.
AB  - It is important to predict the potential of cosmetic ingredients to cause skin
      sensitization, and in accordance with the European Union cosmetic directive for
      the replacement of animal tests, several in vitro tests based on the adverse
      outcome pathway have been developed for hazard identification, such as the direct
      peptide reactivity assay, KeratinoSensTM and the human cell line activation test.
      Here, we describe the development of an artificial neural network (ANN)
      prediction model for skin sensitization risk assessment based on the integrated
      testing strategy concept, using direct peptide reactivity assay, KeratinoSensTM,
      human cell line activation test and an in silico or structure alert parameter. We
      first investigated the relationship between published murine local lymph node
      assay EC3 values, which represent skin sensitization potency, and in vitro test
      results using a panel of about 134 chemicals for which all the required data were
      available. Predictions based on ANN analysis using combinations of parameters
      from all three in vitro tests showed a good correlation with local lymph node
      assay EC3 values. However, when the ANN model was applied to a testing set of 28
      chemicals that had not been included in the training set, predicted EC3s were
      overestimated for some chemicals. Incorporation of an additional in silico or
      structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN
      model improved the results. Our findings suggest that the ANN model based on the
      integrated testing strategy concept could be useful for evaluating the skin
      sensitization potential.

PMID- 29226340
TI  - Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A
      systematic review (2005-2017).
AB  - The objective of this review was to perform a literature compilation of all the
      equine publications that used dexmedetomidine as the first article on this topic
      was published, in 2005. We also aimed to answer the question whether the use of
      dexmedetomidine can currently be justified. For that, we compiled information
      from databases, such as PubMed, Google Scholar and Web of Science and the
      proceedings of the last veterinary anaesthesiology meetings. Dexmedetomidine is
      an attractive drug to be used in horses, mainly due to its pharmacokinetic
      profile and pharmacodynamics that favour its use as intravenous constant rate
      infusion (CRI). Nowadays, its clinical use is popular for sedation in prolonged
      standing procedures and during partial intravenous anaesthesia (PIVA) and total
      intravenous anaesthesia (TIVA). However, legal requirements for its use should be
      taken into account.

PMID- 29226341
TI  - Inflammation and Its Consequences After Surgical Versus Transcatheter Aortic
      Valve Replacement.
AB  - Symptomatic aortic stenosis can be treated by surgical aortic valve replacement
      (SAVR) or transcatheter aortic valve replacement (TAVR), the latter of which is
      regarded as a minimally invasive procedure. Differences between these procedures
      regarding immune responses or changes in coagulation and neurocognitive function
      have thus far been evaluated only sparsely. We carried out a prospective, single
      center, nonrandomized explorative study with 38 patients. Thirteen patients were
      subjected to either SAVR or transfemoral (TF-) TAVR, and 12 patients underwent
      transapical (TA-) TAVR. Plasma cytokines (IL-6, -8, -18, presepsin) and acute
      phase proteins (C-reactive protein, procalcitonin), markers of coagulation and
      platelet function, and neurocognitive function (via various standard tests) were
      assessed before and at five-time points during a 72-h follow-up after surgery.
      SAVR and TA-TAVR patients responded similarly to the procedure in terms of C
      reactive protein, leukocyte numbers, and IL-6, whereas these responses were
      substantially lower in TF-TAVR patients. Only SAVR patients showed measurable IL
      10 levels. SAVR patients without prior anticoagulation experienced a robust and
      transient restoration of platelet function after surgery, with no
      hypercoagulation observable in functional coagulation assays. None of the
      procedures led to an immediate improvement of hand and leg coordination, but
      patients after TA-TAVR had decreased neurocognitive function. Patients after SAVR
      or TA-TAVR exhibit a robust pro-inflammatory response, which is-on the cytokine
      level-counterbalanced only in SAVR patients. Our results point toward a greater
      impact of TA-TAVR on neurocognitive function and indicate a potentially
      detrimental activation of platelets in some patients after SAVR.

PMID- 29226342
TI  - Calcium chloride-enriched calcium aluminate cement promotes in vitro
      osteogenesis.
AB  - AIM: To evaluate the effects of 2.8% or 10% calcium chloride (CaCl2 ) in calcium
      aluminate cement (CAC) with either bismuth oxide (Bi2 O3 ) or zinc oxide (ZnO) as
      radiopacifiers on the progression of osteogenic cell cultures. METHODOLOGY: Rat
      calvaria-derived cells were grown on Thermanox(r) coverslips for 24 h and exposed
      to samples of (i) CACb: with 2.8% CaCl2 and 25% Bi2 O3 ; (ii) CACb+: with 10%
      CaCl2 and 25% Bi2 O3 ; (iii) CACz: with 2.8% CaCl2 and 25% ZnO; or (iv) CACz+:
      with 10% CaCl2 and 25% ZnO, placed on inserts. Nonexposed cultures served as the
      control. Calcium and phosphorus contents in culture media were quantified. The
      effects of the cements on cell apoptosis, cell viability and acquisition of the
      osteogenic cell phenotype were evaluated. Data were compared by Kruskal-Wallis
      test (alpha = 5%). RESULTS: CACb+ promoted the highest levels of calcium in the
      culture media; CACz+, the lowest levels of phosphorus (P < 0.05). CACz+ and CACb
      increased cell apoptosis (P < 0.05). CACb reduced cell viability (P < 0.05) and
      the expression of the osteoblastic phenotype. CACz+ and CACb+ promoted greater
      cell differentiation and matrix mineralization compared to CACz and CACb (P <
      0.05). CONCLUSION: For CAC with the lower CaCl2 content, the use of Bi2 O3 was
      detrimental for osteoblastic cell survival and differentiation compared to ZnO,
      while CAC with the higher CaCl2 content supported the acquisition of the
      osteogenic cell phenotype in vitro regardless of the radiopacifier used. Thus,
      CAC with 10% CaCl2 would potentially promote bone repair in the context of
      endodontic therapies.

PMID- 29226343
TI  - Wide QRS tachycardia with RBBB morphology, right inferior quadrant axis, and 1:1
      AV relation: What is the mechanism?

PMID- 29226344
TI  - Author's Reply.

PMID- 29226345
TI  - Palisading neutrophilic and granulomatous dermatitis as a presentation of Hodgkin
      lymphoma: A case and review.
AB  - Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a histopathological
      diagnosis, characterized by a pattern of granulomatosis, which may be associated
      with leukocytoclastic vasculitis. PNGD most commonly occurs in association with
      systemic inflammatory disorders, typically autoimmune conditions, such as
      rheumatoid arthritis and systemic lupus erythromatosus. There are very rare
      reports of PNGD in patients with lymphoma. We report the case of a 53-year-old
      female with an erythematous, papular eruption occurring in association with
      Hodgkin lymphoma. Histopathological evaluation of the rash confirmed PNGD. To the
      best of our knowledge, this is the first case of PNGD occurring in association
      with Hodgkin lymphoma. Although extremely rare, underlying malignancy should be
      considered in patients with PNGD, particularly in individuals with constitutional
      symptoms and the absence of an obvious inflammatory etiology.

PMID- 29226346
TI  - A multicomponent approach to thinning reinforcer delivery during noncontingent
      reinforcement schedules.
AB  - We evaluated a noncontingent reinforcement procedure that involved initially
      providing three subjects with signaled, continuous access to the functional
      reinforcer for aggression and slowly increasing the amount of time subjects were
      exposed to the signaled unavailability of the reinforcer. Additionally,
      alternative potential reinforcers were available throughout the sessions. Results
      showed immediate and substantial reductions in aggression for all three subjects.
      The clinical utility of this intervention is discussed, and future research
      directions are recommended.

PMID- 29226347
TI  - Job insecurity and depression among automobile sales workers: A longitudinal
      study in South Korea.
AB  - BACKGROUND: Job insecurity, the subjective perception of fear due to uncertainty
      about job continuity, could have long-term health effects. We aimed to examine
      the effect of job insecurity on depression among automobile sales workers in
      South Korea. METHODS: We analyzed data collected in 2007 and 2014 from a
      longitudinal cohort of 560 sales workers from an automobile company in South
      Korea. Change in job insecurity was classified into four groups: secure to
      secure; insecure to secure; secure to insecure; and insecure to insecure.
      RESULTS: After adjusting for potential confounders, workers in the insecure to
      insecure group had a significantly higher likelihood of depression in 2014 than
      workers in the secure to secure group (OR: 2.74; 95%CI: 1.41, 5.31). CONCLUSIONS:
      We found that chronic job insecurity may be a risk factor for developing
      depression among Korean automobile sales workers. This is the first longitudinal
      study examining the association between job insecurity and depression in South
      Korea.

PMID- 29226348
TI  - Sevoflurane induces liver injury by modulating the expression of insulin-like
      growth factor 1 via miR-214.
AB  - This study aimed to detect the effect of sevoflurane anesthesia on liver injury
      through modulating IGF-1. The expression of IGF-1 and IGF-1R in liver tissues of
      sevoflurane-exposed rats was examined by qRT-PCR and Western blot. The expression
      levels of miR-214 in liver cells treated with different concentration of
      sevoflurane at different time points were detected by qRT-PCR. Enzyme-linked
      immunosorbent (ELISA) assay was used to analyze serum IGF-1 concentration in cell
      culture media. After pre-treatment with 100 nM miR-214 inhibitor followed by
      exposure to sevoflurane, the expression level of miR-214 and IGF-1 protein in
      liver cells was examined. Hematoxylin-Eosin (HE) staining and TUNEL assay was
      performed to analyze liver tissue necrosis and apoptosis. The expression levels
      of apoptosis-related proteins (caspase 3 and Bcl-xL) were examined using Western
      blot. The mRNA and protein expression level of IGF-1 and IGF-1R in rats was
      significantly down-regulated after 90 min exposure to sevoflurane. QRT-PCR
      results suggested that exposure to sevoflurane upregulated the expression level
      of miR-214 and decreased the concentration of IGF-1 in a dose and time dependent
      manner. Sevoflurane inhibited the expression of IGF-1 through up-regulating miR
      214. IGF-1 inhibited the positive effect of sevoflurane on cell necrosis and
      apoptosis. Sevoflurane could induce liver injury by modulating IGF-1 expression
      via miR-214.

PMID- 29226349
TI  - What do we know about coaching in medical education? A literature review.
AB  - CONTEXT: Coaching has been employed successfully in the competitive sports,
      professional music, and business and corporate worlds. It is now emerging as a
      training modality in medical education. OBJECTIVES: This paper reviews the
      current evidence on coaching strategies for doctors and medical students.
      METHODS: An applied literature search was conducted in PubMed, MEDLINE and Web of
      Science. Predetermined definitions of coaching interventions and their
      evaluations were used to narrow 993 papers down to 21, which were included in the
      final review. The 21 papers were critiqued with reference to validated scoring
      metrics. RESULTS: There are many papers discussing the merits of coaching in the
      world of medicine, but few evaluations of coaching interventions. Existing
      coaching methodologies can be broadly summarised into three categories: coaching
      for doctor/student well-being and resilience; coaching for improved non-technical
      skills, and coaching for technical skills. Identification of suitable papers for
      inclusion is complicated by theoretical uncertainty regarding coaching: many
      papers use the term as a synonym for teaching or mentoring. The strongest
      evidence for coaching lies in the teaching of technical skills. CONCLUSIONS:
      There is weak- to medium-strength evidence to support coaching as a method of
      improving doctor well-being and enhancing non-technical skills, although the
      evidence base is limited as a whole. This review identifies strong evidence to
      support coaching as a method to improve technical skills. There is great scope
      for further studies investigating the power of coaching in medical students and
      doctors.

PMID- 29226350
TI  - Design and implementation of a novel advanced training curriculum in
      hemoglobinopathies.

PMID- 29226351
TI  - Candidate diagnostic miRNAs that can detect cancer in prostate biopsy.
AB  - BACKGROUND: While histopathological evaluation remains the gold standard for
      diagnosis of prostate cancer (PCa), sampling errors remain a frequent problem;
      therefore, use of tissue biomarkers that can distinguish between benign and
      malignant prostate disease is a potentially beneficial diagnostic strategy.
      METHODS: Deep sequencing of the miRNA transcriptome of 14 benign prostatic
      hyperplasia (BPH) and 60 cancerous and non-cancerous prostate samples extracted
      from 34 cancer-bearing prostates removed by prostatectomy was performed; of the
      latter 60 samples, 16, 21, and 23 samples contained <10%, >30%, and no dysplastic
      cells, respectively. The predictive value of selected miRNAs was then tested by
      quantitative reverse-transcribed PCR (qRT-PCR), using two separate chemistries,
      Exiqon and Taqman, to evaluate the tissue samples obtained by prostatectomy.
      Validation experiments were also performed for a subset of miRNAs by qRT-PCR of
      87 prostate core biopsies. RESULTS: We identified 123 miRNAs significantly
      dysregulated in PCa (adjusted P-values <0.05); 110 and 13 miRNAs were
      dysregulated only in cancerous samples and non-cancerous samples extracted from
      cancer-bearing prostates, respectively, while 31 were dysregulated regardless of
      the dysplastic cell content of the studied specimens. The clinical utility of
      eight selected miRNAs was analyzed using the same sample set with two qRT-PCR
      chemistries. Measurable qRT-PCR signals were obtained for seven and six miRNAs
      using the Exiqon and Taqman chemistries, respectively, and expression levels of
      six and four of these miRNAs differed significantly between BPH and PCa samples,
      regardless of dysplastic cell content. Validation experiments on core biopsies
      using qRT-PCR confirmed differential expression between BPH and PCa of four
      miRNAs (miR-187-3p, miR-183-5p, miR-32-5p, and miR-141-5p) using the Exiqon and
      one miRNA (miR-187-3p) with the Taqman chemistry. CONCLUSIONS: Our sequencing
      analyses identified several candidate diagnostic miRNAs and confirmed some which
      have previously been reported as diagnostic in prostate malignancy. The results
      of this study suggest also that some of selected miRNAs can differentiate between
      non-malignant and malignant prostates even when neoplastic cells are missing from
      the studied specimen.

PMID- 29226352
TI  - Tutorial on kernel estimation of continuous spatial and spatiotemporal relative
      risk.
AB  - Kernel smoothing is a highly flexible and popular approach for estimation of
      probability density and intensity functions of continuous spatial data. In this
      role, it also forms an integral part of estimation of functionals such as the
      density-ratio or "relative risk" surface. Originally developed with the
      epidemiological motivation of examining fluctuations in disease risk based on
      samples of cases and controls collected over a given geographical region, such
      functions have also been successfully used across a diverse range of disciplines
      where a relative comparison of spatial density functions has been of interest.
      This versatility has demanded ongoing developments and improvements to the
      relevant methodology, including use spatially adaptive smoothers; tests of
      significantly elevated risk based on asymptotic theory; extension to the
      spatiotemporal domain; and novel computational methods for their evaluation. In
      this tutorial paper, we review the current methodology, including the most recent
      developments in estimation, computation, and inference. All techniques are
      implemented in the new software package sparr, publicly available for the R
      language, and we illustrate its use with a pair of epidemiological examples.

PMID- 29226354
TI  - Liquid chromatographic methods for the therapeutic drug monitoring of
      methotrexate as clinical decision support for personalized medicine: A brief
      review.
AB  - Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on
      the disease, MTX can be administered at low dose (LDMTX) in some autoimmune
      diseases, like rheumatoid arthritis, or at high dose (HDMTX) in some cancers,
      such as acute lymphoblastic leukemia. After absorption, MTX is metabolized in the
      liver to 7-hydroxymethotrexate and in the intestine to 2,4-diamino-N10
      methylpteroic acid (DAMPA). Moreover, inside red blood cells, MTX is converted to
      active metabolites, MTX polyglutamates (MTXPGs), contributing to its
      pharmacodynamics. Owing to its narrow therapeutic range, and inter- and intra
      patient variability, either noneffectiveness and/or toxicity may occur. Because
      of the existence of a relationship between drug therapeutic outcome and its
      systemic concentration, therapeutic drug monitoring (TDM) may ensure the
      effectiveness and safety of MTX use. In order to monitor the optimization of
      patient clinical response profile, several analytical methods have been described
      for TDM in biological samples. These include liquid chromatography (LC) coupled
      with ultraviolet detection, fluorescence detection or mass spectrometry, each one
      presenting advantages and drawbacks. This paper reviews the most commonly used
      techniques for sample preparation and critically discusses the current LC methods
      applied for the TDM of MTX in biological samples, at LDMTX and HDMTX.

PMID- 29226353
TI  - Biotransformation and metabolic profile of Xian-Ling-Gu-Bao capsule, a
      traditional Chinese medicine prescription, with rat intestinal microflora by
      ultra-performance liquid chromatography coupled with quadrupole time-of-flight
      tandem mass spectrometry analysis.
AB  - Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine
      prescription, has been used for the prevention and treatment of osteoporosis. The
      safety and efficacy of XLGB have been confirmed based on the principle of
      evidence-based medicine. XLGB is usually administered orally, after which its
      multiple components are brought into contact with intestinal microflora in the
      alimentary tract and biotransformed. However, investigations on the comprehensive
      metabolic profile of XLGB are absent. In this study, 12 representative compounds
      bearing different typical structures (including iridoid glycosides, prenylated
      flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal
      saponins, coumarins and monoterpene phenols) were selected and then investigated
      for their biotransformation in rat intestinal microflora. In addition, the
      metabolic profile of XLGB in rat intestinal microflora was investigated by ultra
      performance liquid chromatography coupled with quadrupole time-of-flight tandem
      mass spectrometry. As a result, a total of 87 biotransformation components were
      identified from incubated solutions of 12 representative compounds and XLGB,
      which underwent 16 metabolic reactions (including deglycosylation, glycosylation,
      dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation,
      dehydration, hydration, hydrolysis, methylation, isomerization, cyclization,
      pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction
      with NH3 ). This demonstrated that the deglycosylation reaction by cleavage of
      the sugar moieties is the main metabolic pathway of a variety of glycosides,
      including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides
      and saponins. In addition, compared with the biotransformation of 12
      representative compounds, a different biotransformed fate was observed in the
      XLGB incubated samples of rat intestinal microflora. It is worth noting that the
      amino acid conjugation was first discovered in the metabolism of prenylated
      flavonol glycosides in rat intestinal microflora.

PMID- 29226355
TI  - Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of
      primary school: Population longitudinal study.
AB  - BACKGROUND: Adaptive working memory training is being implemented without an
      adequate understanding of developmental trajectories of working memory. We aimed
      to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and
      visuospatial working memory and (2) whether low verbal and visuospatial working
      memory in Grade 1 predicts low working memory in Grade 3. METHOD: The study
      design includes a population-based longitudinal study of 1,802 children (66%
      uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools
      in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and
      Mister X (visuospatial working memory) screening measures from the Automated
      Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3
      (ages 6-7 and 8-9 years) students. Low working memory was defined as >=1 standard
      deviation below the standard score mean. Descriptive statistics addressed Aim 1,
      and predictive parameters addressed Aim 2. RESULTS: One thousand seventy (59%) of
      1802 Grade 1 participants were reassessed in Grade 3. As expected for typically
      developing children, group mean standard scores were similar in Grades 1 and 3
      for verbal, visuospatial, and overall working memory, but group mean raw scores
      increased markedly. Compared to "not low" children, those classified as having
      low working memory in Grade 1 showed much larger increases in both standard and
      raw scores across verbal, visuospatial, and overall working memory. Sensitivity
      was very low for Grade 1 low working memory predicting Grade 3 low
      classifications. CONCLUSION: Although mean changes in working memory standard
      scores between Grades 1 and 3 were minimal, we found that individual development
      varied widely, with marked natural resolution by Grade 3 in children who
      initially had low working memory. This may render brain-training interventions
      ineffective in the early school year ages, particularly if (as population-based
      programmes usually mandate) selection occurs within a screening paradigm.

PMID- 29226356
TI  - Definition of aggressive periodontitis in periodontal research. A systematic
      review.
AB  - : Since its introduction in 1999, the term aggressive periodontitis (AgP) has
      been the topic of many investigations. Articles supporting the International
      Workshop for a Classification of Periodontal Diseases list several disease
      features, but do not offer operational criteria for identifying cases.
      Consequently, considerable variation in the understanding of AgP can be
      anticipated. AIM: To systematically assess the definitions of AgP reported in
      original periodontal research. METHODS: A systematic review of original research
      on AgP published in English. RESULTS: The electronic search yielded 833
      abstracts. Of these, 472 publications fulfilled the inclusion criteria and were
      appraised. In 26.5% of the publications, no information on AgP operationalization
      is presented, but reference is made to another article. In 12.7% of the
      publications, no information is provided as to how the cases were defined. Many
      combinations of criteria for case definition were found. CONCLUSIONS: This study
      revealed significant heterogeneity in the understanding and use of the term AgP
      in original research and poor documentation of the identification of cases. The
      direction and magnitude of the influence of misclassification and selection bias
      are unknown, but ought to be considered by the critical reader, professionals and
      patients using this term.

PMID- 29226358
TI  - Mechanical Evaluation of Tracheal Grafts on Different Scales.
AB  - Tissue engineered (or bioengineered) tracheas are alternative options under
      investigation when the resection with end-to-end anastomosis cannot be performed.
      One approach to develop bioengineered tracheas is a complex process that involves
      the use of decellularized tissue scaffolds, followed by recellularization in
      custom-made tracheal bioreactors. Tracheas withstand pressure variations and
      their biomechanics are of great importance so that they do not collapse during
      respiration, although there has been no preferred method of mechanical assay of
      tracheas among several laboratories over the years. These methods have been
      performed in segments or whole tracheas and in different species of mammals. This
      article aims to present some methods used by different research laboratories to
      evaluate the mechanics of tracheal grafts and presents the importance of the
      tracheal biomechanics in both macro and micro scales. If bioengineered tracheas
      become a reality in hospitals in the next few years, the standardization of
      biomechanical parameters will be necessary for greater consistency of results
      before transplantations.

PMID- 29226360
TI  - Panel Report, IPA Congress Buenos Aires 2017: How do we understand intimacy from
      an intrapsychic model: Where is the unconscious in the concept of intimacy?

PMID- 29226361
TI  - Contributors and Reviewers for 2017.

PMID- 29226357
TI  - Atrial deformation correlated with functional capacity in mitral stenosis
      patients.
AB  - BACKGROUND: Left atrial (LA) dysfunction, expressed as impaired LA deformation
      using two-dimensional (2D) strain imaging, has been observed in association with
      rheumatic mitral stenosis (MS). However, the clinical role of speckle tracking
      echocardiography (STE)-derived LA strain has rarely been studied in MS. AIM: This
      study aimed to identify the determinants of New York Heart Association (NYHA)
      functional class in patients with mitral stenosis and to investigate the
      relationship between left atrial deformation as measured by two-dimensional STE
      derived LA strain and heart failure symptoms. METHODS: Sixty-nine consecutive
      patients (20 males and 49 females; mean age: 61 +/- 14 years) with rheumatic MS
      were evaluated using comprehensive 2D and color Doppler echocardiography
      including STE-derived LA strain (LAS) and peak positive filling strain rate
      (LASRr) during the LA reservoir phase. Those results were then correlated with
      NYHA functional class. RESULTS: There were 15 (22%) patients in functional class
      I, 42 (61%) in functional class II, and 12 (17%) in functional class III. There
      were no significant differences in mitral valve area, pressure gradient,
      pulmonary artery pressure, LA emptying fraction, or left ventricular ejection
      fraction between functional classes. Upon multivariate analysis (controlling for
      diuretics usage), LAS (beta = -0.233, P = .045) and LASRr (beta = -0.277, P =
      .014) were independent factors in determining NYHA functional class. CONCLUSIONS:
      In stable patients with MS, NYHA functional class independently correlated with
      LAS and LASRr. Left atrial (LA) deformation correlated with heart failure
      symptoms in patients with MS.

PMID- 29226362
TI  - Panel Report, IPA Congress Buenos Aires 2017: Intimacy, primitive communication,
      the psychoanalytic communication.

PMID- 29226363
TI  - Panel Report, IPA Congress Buenos Aires 2017: Listening for echoes of the child
      in adult psychoanalysis.

PMID- 29226364
TI  - Ways of working: A synopsis of contributions to psychoanalytic technique.

PMID- 29226365
TI  - Panel Report, IPA Congress Buenos Aires 2017: Finding unconscious fantasy in the
      intimacy of the analytic encounter.

PMID- 29226367
TI  - Panel Report, IPA Congress Buenos Aires 2017: Intimacy, chronic depression and
      trauma.

PMID- 29226368
TI  - Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the
      regulatory context of Registration, Evaluation, Authorisation, and Restriction of
      Chemicals (REACH).
AB  - In 2013 the Organisation for Economic Co-operation and Development (OECD) test
      guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines
      the acute toxicity of chemicals to embryonic fish. Previous studies show a good
      correlation of FET with the standard acute fish toxicity (AFT) test; however, the
      potential of the FET test to predict AFT, which is required by the Registration,
      Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation (EC
      1907/2006) and the Classification, Labelling and Packaging (CLP) Regulation (EC
      1272/2008), has not yet been fully clarified. In 2015 the European Chemicals
      Agency (ECHA) requested that a consultant perform a scientific analysis of the
      applicability of FET to predict AFT. The purpose was to compare the toxicity of
      substances to fish embryos and to adult fish, and to investigate whether certain
      factors (e.g., physicochemical properties, modes of action, or chemical
      structures) could be used to define the applicability boundaries of the FET test.
      Given the limited data availability, the analysis focused on organic substances.
      The present critical review summarizes the main findings and discusses regulatory
      application of the FET test under REACH. Given some limitations (e.g., neurotoxic
      mode of action) and/or remaining uncertainties (e.g., deviation of some narcotic
      substances), it has been found that the FET test alone is currently not
      sufficient to meet the essential information on AFT as required by the REACH
      regulation. However, the test may be used within weight-of-evidence approaches
      together with other independent, relevant, and reliable sources of information.
      The present review also discusses further research needs that may overcome the
      remaining uncertainties and help to increase acceptance of FET as a replacement
      for AFT in the future. For example, an increase in the availability of data
      generated according to OECD test guideline 236 may provide evidence of a higher
      predictive power of the test. Environ Toxicol Chem 2018;37:657-670. (c) 2017
      SETAC.

PMID- 29226369
TI  - Safety of biologics in psoriasis.
AB  - The advent of biologics brought a paradigm shift in ways to treat psoriatic
      patients because they have dramatic efficacy. At the same time, safety concerns
      about biologics have been raised. In this paper, we focus on the safety profile
      of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two
      tumor necrosis factor-alpha inhibitors; infliximab and adalimumab, one anti
      interleukin (IL)-12/23p40 antibody; ustekinumab, and IL-17 inhibitors;
      secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti-IL
      17A antibodies. Brodalumab is an anti-IL17RA antibody. In this review, we pick up
      topics which have drawn attention regarding the safety of biologics and discuss
      them with recent published work.

PMID- 29226370
TI  - Anti-infliximab antibody concentrations can guide treatment intensification in
      patients with Crohn's disease who lose clinical response.
AB  - BACKGROUND: The presence of antibodies towards infliximab (ATI) is associated
      with lower infliximab (IFX) trough concentrations and loss of response. IFX
      treatment intensification is effective for restoring response in most, but not
      all patients with Crohn's disease (CD). AIM: To compare outcome, pharmacokinetics
      and immunogenicity of treatment intensification strategies in patients with CD
      who lost clinical response to IFX. METHODS: A retrospective cohort study was
      conducted, including 103 patients with CD who lost clinical response during IFX
      maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a
      next infusion after a shortened interval. IFX and ATI concentrations were
      measured in consecutive trough samples, just before (T0) and after (T+1)
      treatment intensification. RESULTS: Clinical response (physicians' global
      assessment) and biological response and remission (CRP) were restored in 63%, 42%
      and 24% of patients (evaluated at T+1). Treatment intensification increased IFX
      trough concentrations from 1.2 MUg/mL [0.3-3.6] at T0 to 3.6 MUg/mL [0.5-10.2] at
      T+1 (P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample
      of 47% of patients. ATI negatively impacted the achieved IFX trough concentration
      (Spearman r -0.57, P < .0001) and the probability of clinical response (P =
      0.034) at T+1. When ATI were quantifiable but <282 ng/mL eq. at T0, combined
      interval shortening and dose doubling was more effective for restoring
      therapeutic IFX trough concentrations (>=3 MUg/mL at T+1) than dose doubling
      alone, which in turn was more effective than interval shortening alone (P <
      .001). CONCLUSION: Antibodies towards infliximab can guide clinical decision
      making on treatment intensification.

PMID- 29226371
TI  - The epidemiology of transfusion: where blood goes and why we should care about
      it.

PMID- 29226373
TI  - Just chill-it's worth it!

PMID- 29226372
TI  - Hypertriglyceridemia in pregnancy.

PMID- 29226375
TI  - Da Luz LT, Marchand M, Nascimento B, Tien H, Nathens A, Shah P, Efficacy and
      safety of the drugs used to reverse the direct oral anticoagulants: a systematic
      review and meta-analyses. TRANSFUSION 2017;57:1834-46.

PMID- 29226374
TI  - The perils of storing thawed cryoprecipitate in the refrigerator.

PMID- 29226377
TI  - Two- and three-dimensional transthoracic echocardiographic assessment of superior
      vena cava, crista terminalis, and right atrial appendage using the right
      parasternal approach.
AB  - BACKGROUND: The noninvasive assessment of superior vena cava (SVC), crista
      terminalis (CT), and the right atrial appendage (RAA) has clinical implications
      in determining the right atrium (RA) pressure in adult patients in whom the
      inferior vena cava cannot be imaged, in planning electrophysiological procedures
      and for evaluation of thrombi in RA/RAA. It is difficult to image these
      structures using standard two-dimensional transthoracic echocardiography (2DTTE),
      but the right parasternal approach has shown promise in the very few studies
      published so far. AIM: The aim of this study was to show the feasibility of this
      approach and its usefulness in qualitative and quantitative assessments of these
      structures by both 2D and three (3D) TTE in patients with and without known
      cardiac pathologies. MATERIAL AND METHODS: The study consisted of 38 adult
      patients, 17 of whom had cardiac pathologies (Group 1) while the remainder (Group
      2) had no evidence of heart disease clinically or by echocardiography. RESULTS
      AND CONCLUSION: Both SVC and RAA could be imaged by 2DTTE and 3DTTE in 53% of 40
      patients (two separate groups of 20 consecutive patients) studied demonstrating
      the technical feasibility of this approach. SVC size and collapsibility, CT and
      RAA size, and RAA fractional shortening were evaluated in both groups by both 2D
      and 3DTTE. 3DTTE provided incremental value over 2DTTE by its ability to view en
      face the SVC in short axis and the base of RAA and RAA volumes resulting in more
      comprehensive assessment of their size and function.

PMID- 29226378
TI  - Origin and transformation of the in-flight wing-coupling structure in Psocodea
      (Insecta: Paraneoptera).
AB  - Many four-winged insects have mechanisms that unite the forewings and hindwings
      in a single plane. Such an in-flight wing coupling apparatus may improve flight
      performance in four-winged insects, but its structure is variable among different
      insect groups. The wings of bark lice (Insecta: Psocodea: "Psocoptera") also have
      an in-flight wing coupling apparatus, but to date, its morphology has not been
      studied in detail. In this study, we examined the wing-coupling structure in
      representative species of the three suborders of bark lice (Trogiomorpha,
      Troctomorpha, and Psocomorpha) and inferred its origin and transformation. We
      conclude that the main component of the psocodean wing coupling apparatus evolved
      once in the common ancestor via modification of cuticular structures at the apex
      of the forewing CuP vein. Morphological differences in components of the coupling
      structures are phylogenetically informative at the intraorder level and include
      an autapomorphy that characterizes Troctomorpha and a synapomorphy that supports
      a sister relationship between Troctomorpha and Psocomorpha.

PMID- 29226379
TI  - Pure erythroid leukemia.

PMID- 29226380
TI  - Acute severe mitral regurgitation after blunt chest trauma.
AB  - Myocardial contusion and aortic injury are well-known cardiac complications of
      blunt chest trauma, but valvular injury is rare. Traumatic valve injuries most
      commonly involve the aortic valve, with isolated mitral valve injury being quite
      rare. We report a case of acute severe mitral regurgitation due to ruptured
      chordae tendineae requiring surgical repair following a motor vehicle accident.

PMID- 29226382
TI  - Substantial injuries influence ranking position in young elite athletes of
      athletics, cross-country skiing and orienteering.
AB  - The relationship between injury and performance in young athletes is scarcely
      studied. The aim of this study was therefore to explore the association between
      injury prevalence and ranking position among adolescent elite athletes. One
      hundred and sixty-two male and female adolescent elite athletes (age range 15
      19), competing in athletics (n = 59), cross-country skiing (n = 66), and
      orienteering (n = 37), were monitored weekly over 22-47 weeks using a web-based
      injury questionnaire. Ranking lists were collected. A significant (P = .003)
      difference was found in the seasonal substantial injury prevalence across the
      ranked athletes over the season, where the top-ranked (median 3.6%, 25-75th
      percentiles 0%-14.3%) and middle-ranked athletes (median 2.3%, 25-75th
      percentiles 0%-10.0%) had a lower substantial injury prevalence compared to the
      low-ranked athletes (median 11.3%, 25-75th percentiles 2.5%-27.1%), during both
      preseason (P = .002) and competitive season (P = .031). Athletes who improved
      their ranking position (51%, n = 51) reported a lower substantial injury
      prevalence (median 0%, 25-75th percentiles 0%-10.0%) compared to those who
      decreased (49%, n = 49) their ranking position (md 6.7%, 25-75th percentiles 0%
      22.5%). In the top-ranked group, no athlete reported substantial injury more than
      40% of all data collection time points compared to 9.6% (n = 5) in the middle
      ranked, and 17.3% (n = 9) in the low-ranked group. Our results provide supporting
      evidence that substantial injuries, such as acute and overuse injuries leading to
      moderate or severe reductions in training or sports performance, influence
      ranking position in adolescent elite athletes. The findings are crucial to
      stakeholders involved in adolescent elite sports and support the value of
      designing effective preventive interventions for substantial injuries.

PMID- 29226381
TI  - A robust and powerful two-step testing procedure for local ancestry adjusted
      allelic association analysis in admixed populations.
AB  - Genetic association studies in admixed populations allow us to gain deeper
      understanding of the genetic architecture of human diseases and traits. However,
      population stratification, complicated linkage disequilibrium (LD) patterns, and
      the complex interplay of allelic and ancestry effects on phenotypic traits pose
      challenges in such analyses. These issues may lead to detecting spurious
      associations and/or result in reduced statistical power. Fortunately, if handled
      appropriately, these same challenges provide unique opportunities for gene
      mapping. To address these challenges and to take these opportunities, we propose
      a robust and powerful two-step testing procedure Local Ancestry Adjusted Allelic
      (LAAA) association. In the first step, LAAA robustly captures associations due to
      allelic effect, ancestry effect, and interaction effect, allowing detection of
      effect heterogeneity across ancestral populations. In the second step, LAAA
      identifies the source of association, namely allelic, ancestry, or the
      combination. By jointly modeling allele, local ancestry, and ancestry-specific
      allelic effects, LAAA is highly powerful in capturing the presence of interaction
      between ancestry and allele effect. We evaluated the validity and statistical
      power of LAAA through simulations over a broad spectrum of scenarios. We further
      illustrated its usefulness by application to the Candidate Gene Association
      Resource (CARe) African American participants for association with hemoglobin
      levels. We were able to replicate independent groups' previously identified loci
      that would have been missed in CARe without joint testing. Moreover, the loci,
      for which LAAA detected potential effect heterogeneity, were replicated among
      African Americans from the Women's Health Initiative study. LAAA is freely
      available at https://yunliweb.its.unc.edu/LAAA.

PMID- 29226383
TI  - Bifidobacteria alleviate experimentally induced colitis by upregulating
      indoleamine 2, 3-dioxygenase expression.
AB  - The goal of this study was explore the role of indoleamine 2, 3-dioxygenase (IDO)
      in the therapeutic effect of probiotics on inflammatory bowel disease (IBD).
      Trinitrobenzene sulfonic acid (TNBS) was used to induce colitis in mice and 1
      methyltryptophan (1-MT) to block expression of IDO. Clinical manifestations and
      macroscopic and microscopic colonic changes were assessed using a disease
      activity index (DAI), the Wallace-Keenan, and Curtner scoring systems,
      respectively. Expression of colonic IDO was detected by western blot.
      Immunohistochemistry analysis to evaluate numbers of CD11c+ cells and expression
      of IL-17 and Foxp3 showed that DAI, Wallace-Keenan, and Curtner scores were lower
      in the Bifidobacteria treatment group than the control group and that the
      therapeutic effect of Bifidobacteria was blocked by 1-MT (P < 0.05).
      Additionally, Bifidobacteria were found to increase expression of IDO and the
      numbers of CD11c+ cells, CD11c+ and IDO double positive cells and Foxp3+ Treg
      cells, while decreasing the number of IL-17+ cells (P < 0.05). The generation of
      Foxp3+ Treg cells induced by Bifidobacteria was abrogated by 1-MT (P < 0.05).
      These findings study suggest that Bifidobacteria attenuate TNBS-induced colitis
      by inducing expression of IDO, which further increases generation of Foxp3+ Treg
      cells.

PMID- 29226384
TI  - The impact of volume overload on right heart function in end-stage renal disease
      patients on hemodialysis.
AB  - PURPOSE: The aim of this study was to evaluate the impact of volume overload on
      echocardiographic parameters used for the assessment of the right ventricle (RV)
      and right atrium (RA), to determine volume-independent parameters and to
      noninvasively investigate the physio-mechanics of RV and RA by examining end
      stage kidney patients before and after hemodialysis (HD). METHODS: The
      echocardiographic images were obtained from 67 patients (49.2 +/- 17.3 years, 23
      f) before and after HD. Changes in echocardiographic parameters with HD were
      examined. The average ultrafiltrated volume was 3088.1 +/- 1103.7 mL. RESULTS:
      The size of RV and RA and tricuspid annular plane systolic excursion (TAPSE)
      decreased after HD, whereas myocardial performance index increased. RV fractional
      area change and iso-volumetric contraction acceleration time remained unchanged.
      RV global longitudinal strain (GLS) and RV early diastolic strain rate (SR)
      decreased after HD. Systolic and late diastolic SR of the RV showed no
      statistically significant difference after HD. Longitudinal strain and SR of RA
      contraction were not significantly different after HD. The changes in RV GLS (r =
      .641, P = .027), RV free wall longitudinal strain (r = .643, P < .001), RA
      reservoir phase strain (r = .60, P = .008), and TAPSE (r = .642, P = .001)
      significantly correlated with ultrafiltrated volume. CONCLUSION: Two-dimensional
      speckle tracking echocardiography is an easy and noninvasive tool that could
      provide additional volume-independent echocardiographic parameters and more
      information on RA physio-mechanics. This might lead to a better evaluation of the
      cardiac pathophysiology and hemodynamics of patients. Moreover, providing novel
      volume-independent parameters for the evaluation of right heart chambers would
      improve the clinical perspectives of patients.

PMID- 29226386
TI  - Theranostic 2D Tantalum Carbide (MXene).
AB  - The large-dimensional and rigid ceramic bulks fabricated by high-temperature
      solid-phase reaction and sintering have never been considered for possibly
      entering and circulating within the blood vessels for biomedical applications,
      especially on combating cancer. Here, it is reported for the first time that MAX
      ceramic biomaterials exhibit unique functionalities for dual-mode
      photoacoustic/computed tomography imaging and are highly effective for in vivo
      photothermal ablation of tumors upon being exfoliated into ultrathin nanosheets
      within atomic thickness (MXene). As a paradigm, 2D ultrathin tantalum carbide
      nanosheets (Ta4 C3 MXenes) with nanosized lateral sizes are successfully
      synthesized based on a two-step liquid exfoliation strategy of MAX phase Ta4 AlC3
      by combined hydrofluoric acid (HF) etching and probe sonication. The structural,
      electronic, and surface characteristics of the as-exfoliated nanosheets are
      revealed by various characterizations combined with first-principles calculations
      via density functional theory. Especially, the superior photothermal-conversion
      performance (efficiency eta of 44.7%) and in vitro/in vivo photothermal ablation
      of tumor by biocompatible soybean phospholipid-modified Ta4 C3 nanosheets are
      systematically revealed and demonstrated. Based on the large family members of
      MXenes, this work may offer a paradigm that MXenes can achieve the specific
      biomedical applications (here, theranostic) providing that their compositions and
      nanostructures are carefully tuned and optimized to meet the strict requirements
      of biomedicine.

PMID- 29226385
TI  - Methods for meta-analysis of multiple traits using GWAS summary statistics.
AB  - Genome-wide association studies (GWAS) for complex diseases have focused
      primarily on single-trait analyses for disease status and disease-related
      quantitative traits. For example, GWAS on risk factors for coronary artery
      disease analyze genetic associations of plasma lipids such as total cholesterol,
      LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However,
      traits are often correlated and a joint analysis may yield increased statistical
      power for association over multiple univariate analyses. Recently several
      multivariate methods have been proposed that require individual-level data. Here,
      we develop metaUSAT (where USAT is unified score-based association test), a novel
      unified association test of a single genetic variant with multiple traits that
      uses only summary statistics from existing GWAS. Although the existing methods
      either perform well when most correlated traits are affected by the genetic
      variant in the same direction or are powerful when only a few of the correlated
      traits are associated, metaUSAT is designed to be robust to the association
      structure of correlated traits. metaUSAT does not require individual-level data
      and can test genetic associations of categorical and/or continuous traits. One
      can also use metaUSAT to analyze a single trait over multiple studies,
      appropriately accounting for overlapping samples, if any. metaUSAT provides an
      approximate asymptotic P-value for association and is computationally efficient
      for implementation at a genome-wide level. Simulation experiments show that
      metaUSAT maintains proper type-I error at low error levels. It has similar and
      sometimes greater power to detect association across a wide array of scenarios
      compared to existing methods, which are usually powerful for some specific
      association scenarios only. When applied to plasma lipids summary data from the
      METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci
      beyond the ones identified by univariate analyses. Evidence from larger studies
      suggest that the variants additionally detected by our test are, indeed,
      associated with lipid levels in humans. In summary, metaUSAT can provide novel
      insights into the genetic architecture of a common disease or traits.

PMID- 29226387
TI  - Systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by
      vasculopathy and tissue fibrosis of the skin and various internal organs. A
      series of genetic and epidemiological studies have demonstrated that SSc onset is
      determined by the accumulation of predisposing factors related to environmental
      influences, while genetic factors affect the susceptibility to and the severity
      of this disease. This notion has been confirmed by recent advance in animal
      models. The initial trigger of SSc is believed to be autoimmune attacks to
      endothelial cells, which occur in individuals with the genetic susceptibility to
      autoimmune diseases and/or the cumulative exposure to certain SSc-related
      environmental influences. Then, endothelial cells are aberrantly activated or
      damaged, leading to the development of vascular structural changes, such as
      destructive vasculopathy and proliferative obliterative vasculopathy, and tissue
      fibrosis. In parallel, inflammatory cells activate SSc fibroblasts and modify the
      metabolism of extracellular matrix by soluble factors and autoantibodies. Prior
      to or during these processes, SSc fibroblasts acquire the ability to selectively
      respond to profibrotic growth factors and cytokines, persistently producing
      excessive amount of extracellular matrix. SSc fibroblasts also modify immune
      responses, at least those of CD4+ T cells, in the microenvironment through the
      secretion of immune regulatory molecules. Thus, various types of individually
      activated cells interact with each other and coordinately drive an SSc-specific
      disease cascade, leading to the development of unique clinical symptoms. This
      article provides an overview of the current understanding of the pathogenesis of
      SSc with the recent advance in the research field of this disease.

PMID- 29226388
TI  - A Carbonyl Compound-Based Flexible Cathode with Superior Rate Performance and
      Cyclic Stability for Flexible Lithium-Ion Batteries.
AB  - A sulfur-linked carbonyl-based poly(2,5-dihydroxyl-1,4-benzoquinonyl sulfide)
      (PDHBQS) compound is synthesized and used as cathode material for lithium-ion
      batteries (LIBs). Flexible binder-free composite cathode with single-wall carbon
      nanotubes (PDHBQS-SWCNTs) is then fabricated through vacuum filtration method
      with SWCNTs. Electrochemical measurements show that PDHBQS-SWCNTs cathode can
      deliver a discharge capacity of 182 mA h g-1 (0.9 mA h cm-2 ) at a current rate
      of 50 mA g-1 and a potential window of 1.5 V-3.5 V. The cathode delivers a
      capacity of 75 mA h g-1 (0.47 mA h cm-2 ) at 5000 mA g-1 , which confirms its
      good rate performance at high current density. PDHBQS-SWCNTs flexible cathode
      retains 89% of its initial capacity at 250 mA g-1 after 500 charge-discharge
      cycles. Furthermore, large-area (28 cm2 ) flexible batteries based on PDHBQS
      SWCNTs cathode and lithium foils anode are also assembled. The flexible battery
      shows good electrochemical activities with continuous bending, which retains 88%
      of its initial discharge capacity after 2000 bending cycles. The significant
      capacity, high rate performance, superior cyclic performance, and good
      flexibility make this material a promising candidate for a future application of
      flexible LIBs.

PMID- 29226390
TI  - Decision shaping neutrophil-platelet interplay in inflammation: From physiology
      to intervention.
AB  - Inflammation is a well-coordinated process in response to tissue injury or
      infection aimed at restoration of tissue homoeostasis. Platelets and neutrophils
      are typically viewed important in the context of haemostasis and bacterial
      killing, respectively. However, as these cells are equipped with readily
      available armoury, both have received much attention for their importance in
      shaping the early inflammatory reaction in recent years. While some of these
      activities are executed individually, both cells join forces during much of their
      pro-inflammatory activities. This brief review summarizes recently identified
      mechanisms of neutrophil-platelet interaction and describes functional
      consequences on neutrophil trafficking and the release of neutrophil
      extracellular traps. Moreover, the synergy of neutrophils and platelets during
      the recruitment of monocytes is reviewed. Finally, this review discusses how
      knowledge on the intimate neutrophil-platelet partnership can be employed to
      design interventional strategies.

PMID- 29226389
TI  - Left posterior fascicular ventricular tachycardia: Ablative strategies.

PMID- 29226391
TI  - Experience with leflunomide as treatment and as secondary prophylaxis for
      cytomegalovirus infection in lung transplant recipients: A case series and review
      of the literature.
AB  - BACKGROUND: Data concerning the use of leflunomide-a drug approved for rheumatoid
      arthritis with in vitro anticytomegalovirus (CMV) activity-in lung transplant
      (LT) recipients are scarce. AIMS: To report the use of leflunomide in LT
      recipients diagnosed with CMV infection/disease. MATERIAL AND METHODS: We
      performed a single-center retrospective study including LT recipients who
      received leflunomide for CMV infection or as secondary prophylaxis after viremia
      clearance. We also conducted a full systematic PubMed search until June 30, 2017.
      RESULTS: We identified 5 LT recipients in our center plus 7 patients reported in
      the literature. All patients had previously received ganciclovir (GCV) and
      foscarnet (FOS), with drug-induced adverse effects described in 6 recipients
      (50%). Antiviral resistance mutations were observed in 8 patients (66.7%).
      Leflunomide was prescribed for CMV infection in 9 of 12 patients (75%) and as
      secondary prophylaxis in 3 patients (25%). Initial decrease of CMV viremia after
      starting leflunomide was observed in 7 of 9 recipients (77.7%), although this
      response was only transient in 2 patients. Long-term suppression of CMV viremia
      was reported in 7 of 12 patients (58.3%). In 3 recipients (25%), leflunomide was
      discontinued due to adverse effects. DISCUSSION: Our study has some limitations,
      such as the small number of patients included, its retrospective nature, and
      absence of leflunomide drug monitoring in serum. Notwithstanding, in our
      experience, leflunomide proved to be particularly effective as an anti-CMV
      secondary prophylaxis treatment and for clearing low-grade viremia. Moreover,
      leflunomide combined with a short course of GCV or intravitreal FOS also proved
      to be very effective in some patients. CONCLUSION: Leflunomide, alone or in
      combination, could be an effective treatment in selected LT recipients with GCV
      resistant CMV infection and as secondary prophylaxis. Further studies are
      necessary.

PMID- 29226392
TI  - Critical Role of Interface and Crystallinity on the Performance and
      Photostability of Perovskite Solar Cell on Nickel Oxide.
AB  - Hybrid perovskites are on a trajectory toward realizing the most efficient single
      junction, solution-processed photovoltaic devices. However, a critical issue is
      the limited understanding of the correlation between the degree of crystallinity
      and the emergent perovskite/hole (or electron) transport layer on device
      performance and photostability. Here, the controlled growth of hybrid perovskites
      on nickel oxide (NiO) is shown, resulting in the formation of thin films with
      enhanced crystallinity with characteristic peak width and splitting reminiscent
      of the tetragonal phase in single crystals. Photophysical and interface sensitive
      measurements reveal a reduced trap density at the perovskite/NiO interface in
      comparison with perovskites grown on poly(3,4-ethylene dioxy thiophene)
      polystyrene sulfonate. Photovoltaic cells exhibit a high open circuit voltage
      (1.12 V), indicating a near-ideal energy band alignment. Moreover, photostability
      of photovoltaic devices up to 10-Suns is observed, which is a direct result of
      the superior crystallinity of perovskite thin films on NiO. These results
      elucidate the critical role of the quality of the perovskite/hole transport layer
      interface in rendering high-performance and photostable optoelectronic devices.

PMID- 29226393
TI  - Analysis of ABO chimera from peripheral red cells and reticulocytes by flow
      cytometry and micro gel column technique in patients post-ABO-incompatible HSCT.
AB  - BACKGROUND: How to choose an appropriate method to monitoring dynamic ABO chimera
      post-ABO-incompatible HSCT is crucial to not only assess the status of erythroid
      engraftment but also achieve personalized safety transfusion. METHODS: We
      evaluated the efficacy of micro gel column technique (MGCT) and flow cytometry
      (FCM) by series of artificial ABO chimera mixtures from 0.5% to 50% and by
      investigating 15 cases of ABO-incompatible HSCT patients with longitudinally ABO
      blood grouping and ABO chimera from RBCs and reticulocytes. RESULTS: 5% and 2% of
      ABO chimera mixtures can be efficiently detected by MGCT and FCM, respectively.
      6.3% of donor RBCs with 44.77% of donor reticulocytes in the early phase and 7.9%
      of patient RBCs with 96% of donor reticulocytes in the phase of complete donor
      type can be detected by FCM rather than failure by MGCT simultaneously. However,
      in case 8#, 8.6% of donor reticulocytes rather than 99.1% of donor RBCs on the
      98th day post-HSCT could adequately predict early relapse. CONCLUSIONS:
      Investigation of ABO chimera from reticulocytes by FCM is a more effective
      strategy rather than ABO blood grouping and RBCs by FCM to indicate the true
      progress of erythroid alteration and achieve personalized safety transfusion post
      ABO-incompatible HSCT.

PMID- 29226394
TI  - 3D Mesoporous van der Waals Heterostructures for Trifunctional Energy
      Electrocatalysis.
AB  - The emergence of van der Waals (vdW) heterostructures of 2D materials has opened
      new avenues for fundamental scientific research and technological applications.
      However, the current concepts and strategies of material engineering lack
      feasibilities to comprehensively regulate the as-obtained extrinsic
      physicochemical characters together with intrinsic properties and activities for
      optimal performances. A 3D mesoporous vdW heterostructure of graphene and
      nitrogen-doped MoS2 via a two-step sequential chemical vapor deposition method is
      constructed. Such strategy is demonstrated to offer an all-round engineering of
      2D materials including the morphology, edge, defect, interface, and electronic
      structure, thereby leading to robustly modified properties and greatly enhanced
      electrochemical activities. The hydrogen evolution is substantially accelerated
      on MoS2 , while the oxygen reduction and evolution are significantly improved on
      graphene. This work provides a powerful overall engineering strategy of 2D
      materials for electrocatalysis, which is also enlightening for other
      nanomaterials and energy-related applications.

PMID- 29226395
TI  - Letter: the neglected analgesic properties of red pepper in the clinical
      management of the irritable bowel syndrome pain-Authors' reply.

PMID- 29226396
TI  - Editorial: alfapump-an alternative to large-volume paracentesis for patients with
      refractory ascites?

PMID- 29226397
TI  - Letter: biologics treatment in Crohn's disease and risk of bowel resection-what
      about the patients who stop anti-TNF therapy?

PMID- 29226398
TI  - Editorial: recurrence of Helicobacter pylori infection-still the same after all
      these years....

PMID- 29226399
TI  - Letter: the neglected analgesic properties of red pepper in the clinical
      management of the irritable bowel syndrome pain.

PMID- 29226400
TI  - Letter: gastric atrophy assessment-merging serology, endoscopy and histology in
      clinical practice.

PMID- 29226401
TI  - Editorial: a step forward in refining prognostication for patients with HIV
      associated hepatocellular carcinoma-Authors' reply.

PMID- 29226402
TI  - Letter: biologics treatment in Crohn's disease and risk of bowel resection-what
      about the patients who stop anti-TNF therapy? Authors' reply.

PMID- 29226403
TI  - Letter: oesophageal histological abnormalities and GERD - an underestimated
      relationship requiring more attention.

PMID- 29226405
TI  - Editorial: anti-TNF therapy and myopenia in Crohn's disease-another step towards
      personalised medicine. Authors' reply.

PMID- 29226406
TI  - Letter: thiopurines - is less really more?

PMID- 29226407
TI  - Editorial: recurrence of Helicobacter pylori infection-still the same after all
      these years... Authors' reply.

PMID- 29226408
TI  - Editorial: long-term effectiveness of elimination diet therapy for eosinophilic
      oesophagitis-is the glass half full or half empty?

PMID- 29226409
TI  - Editorial: thiopurine-induced myelosuppression and infections in inflammatory
      bowel disease patients with a normal TPMT genotype-the perils of ageing.

PMID- 29226410
TI  - Editorial: alfapump-an alternative to large-volume paracentesis for patients with
      refractory ascites? Authors' reply.

PMID- 29226411
TI  - Editorial: Non-breaking news! High-dose PPIs likely do not cause fractures.

PMID- 29226412
TI  - Editorial: anti-TNF therapy and myopenia in Crohn's disease-another step towards
      personalised medicine.

PMID- 29226413
TI  - Corrigendum.

PMID- 29226414
TI  - Editorial: a step forward in refining prognostication for patients with HIV
      associated hepatocellular carcinoma.

PMID- 29226415
TI  - Letter: thiopurines - is less really more? Authors' reply.

PMID- 29226416
TI  - Editorial: patient assessment of constipation-symptoms (PAC-SYM) questionnaire
      has a minimal important difference.

PMID- 29226418
TI  - Corrigendum.

PMID- 29226417
TI  - Editorial: avoiding corticosteroids in the treatment of inflammatory bowel
      disease-Author's reply.

PMID- 29226419
TI  - Alimentary Pharmacology and Therapeutics in 2018 - big changes but much the same.

PMID- 29226420
TI  - Editorial: thiopurine-induced myelosuppression and infections in inflammatory
      bowel disease patients with a normal TPMT genotype-the perils of ageing. Authors'
      reply.

PMID- 29226421
TI  - Editorial: avoiding corticosteroids in the treatment of inflammatory bowel
      disease.

PMID- 29226422
TI  - Pathogenesis of psoriasis and development of treatment.
AB  - The pathogenesis of psoriasis can be explained by dysregulation of immunological
      cell function as well as keratinocyte proliferation/differentiation. Recently,
      the immunological pathomechanism has been clarified substantially. Whereas T
      helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has
      been demonstrated that Th17 cells play a key role. Th17 development is maintained
      by interleukin (IL)-23 mainly produced by dendritic cells. Th17 cells produce
      various cytokines, including IL-17A, IL-17F and IL-22. IL-17A and IL-22 induce
      not only keratinocyte proliferation, but also tumor necrosis factor (TNF)-alpha,
      chemokine (C-X-C motif) ligand (CXCL)1 and CXCL8 production. TNF-alpha
      accelerates the infiltration of inflammatory cells, including lymphocytes,
      monocytes and neutrophils, from the peripheral blood into skin with dendritic
      cell activation. In addition, antimicrobial peptides are overexpressed in
      psoriatic skin lesions, and the antimicrobial peptide, LL-37, activates dendritic
      cells, which leads to the development of inflammation. Furthermore, activation of
      nuclear factor-kappaB signal induces the expression of keratins 6 and 16 in
      keratinocytes, which are associated with acanthosis and reduced turnover time in
      the epidermis. The progression of the pathomechanism contributes to the
      development of new therapies for psoriasis.

PMID- 29226423
TI  - Patellar tendinopathy with intratendinous alteration on MRI may be related to
      patellofemoral dysplasia.
AB  - Patellar tendinopathy (PT) is a frequent overuse injury of the extensor knee
      apparatus, whereas as up to 30% of the athletes might suffer from persisting
      symptoms during their entire career. In the present case-control study, 47
      patients (30.8 +/- 11.4 years) with PT with intratendinous alteration (PTita) of
      a minimum of >=25% of the axial surface on MRI and minimum Blazina score of II
      (pain during without limiting sports activity) were included; MR images were
      analyzed for trochlear geometry, patellar height/tilt, and tibial tubercle
      trochlear groove distance (TT-TG). The control group (CG) comprised 87 age- and
      gender-matched patients without history of anterior knee pain or lateral patellar
      instability. It was hypothesized that patients with PT might be related to
      patellofemoral dysplasia. It was found that the patella was significantly higher
      in patients with PT compared to the CG (patellotrochlear index [PT-I]: 0.33 vs
      0.37, P = .014; Insall-Salvati index [InSa]: 1.18 vs 1.07, P = .004). PT-I was
      above the cut-off value in 10.6% of PT knees (CG 5.7%, P = .27), and InSa in
      42.6% (CG 21.8%, P = .012). TT-TG was significantly higher in patients with PT
      compared to CG (12.0 mm vs 9.9 mm, P = .002); however, TT-TG was only pathologic
      (>20 mm) in one patient. The trochlear facet ratio was above the cut-off value in
      55.3% of PT patients and 23% of CG (P < .001), and was significantly greater in
      patients with PT (0.39 +/- 0.09) than CG (0.48 +/- 0.1, P < .001). Knees with PT
      have significantly more morphological characteristics of patellofemoral
      instability, which needs to be considered especially in recurrent or treatment
      refractive cases.

PMID- 29226424
TI  - Activation of EP2 receptor suppresses poly(I: C) and LPS-mediated inflammation in
      primary microglia and organotypic hippocampal slice cultures: Contributing role
      for MAPKs.
AB  - Brain inflammation is a critical factor involved in neurodegeneration. Recently,
      the prostaglandin E2 (PGE2 ) downstream members were suggested to modulate
      neuroinflammatory responses accompanying neurodegenerative diseases. In this
      study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2
      ) during TLR3 and TLR4-driven inflammatory response using in vitro primary
      microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion
      of microglia from OHSCs differentially affected TLR3 and TLR4 receptor
      expression. Poly(I:C) induced the production of prostaglandin E2 in OHSCs by
      increasing cyclooxygenase (COX-2) and microsomal prostaglandin E synthase (mPGES)
      1. Besides, stimulation of OHSCs and microglia with Poly(I:C) upregulated EP2
      receptor expression. Co-stimulation of OHSCs and microglia with the EP2 agonist
      butaprost reduced inflammatory mediators induced by LPS and Poly(I:C). In
      Poly(I:C) challenged OHSCs, butaprost almost restored microglia ramified
      morphology and reduced Iba1 immunoreactivity. Importantly, microglia depletion
      prevented the induction of inflammatory mediators following Poly(I:C) or LPS
      challenge in OHSCs. Activation of EP2 receptor reversed the Poly(I:C)/LPS-induced
      phosphorylation of the mitogen activated protein kinases (MAPKs) ERK, p38 MAPK
      and c-Jun N-terminal kinase (JNK) in microglia. Collectively, these data identify
      an anti-inflammatory function for EP2 signaling in diverse innate immune
      responses, through a mechanism that involves the mitogen-activated protein
      kinases pathway.

PMID- 29226425
TI  - Intraventricular melanocytoma diagnosis confirmed by gene mutation profile.
AB  - Primary leptomeningeal melanocytic tumors (PLMTs) are rare. They usually arise
      along the spinal cord and at the skull base. Here we report on a patient with a
      very rare intraventricular melanocytoma. Histologically, a melanocytic tumor was
      clearly diagnosed. However, to make the uncommon diagnosis of an intraventricular
      melanocytoma, metastatic melanoma needed to be excluded. Next generation
      sequencing covering gene mutations that may occur in PLMTs and cutaneous melanoma
      was performed. The unique gene mutation profile detected, consisting of an
      activating CYSLTR2 L129Q mutation and EIF1AX G9R mutation and a lack of mutations
      in genes known to occur in metastatic melanoma (i.e. BRAF or NRAS) confirmed the
      diagnosis of an intraventricular melanocytoma. This case report is the second
      intraventricular melanocytoma published to date and demonstrates the value of
      applying novel genetic assays to make this diagnosis.

PMID- 29226426
TI  - Significance of thrombocytopenia in patients with primary and postessential
      thrombocythemia/polycythemia vera myelofibrosis.
AB  - Severe thrombocytopenia (platelets <50 * 109 /L) is associated with very poor
      outcome of patients with myelofibrosis (MF). As patients with primary
      myelofibrosis (PMF) differ from patients with postessential thrombocythemia (PET
      MF) and postpolycythemia vera myelofibrosis (PPV-MF), we aimed to evaluate the
      significance of low platelets among these patients. We present clinical
      characteristics and outcome of patients with either PMF, PPV-MF, or PET-MF, and
      thrombocytopenia who presented to our institution between 1984 and 2015. Of 1269
      patients (877 PMF, 212 PPV-MF, 180 PET-MF), 11% and 14% had platelets either <50
      * 109 /L or between 50-100 * 109 /L, respectively. Patients with platelets <50 *
      109 /L were most anemic and transfusion dependent, had highest blast count and
      unfavorable karyotype. In general, their overall and leukemia-free survival was
      the shortest with median time of 15 and 13 months, respectively; with incidence
      of acute leukemia almost twice as high as in the remaining patients (6.9 vs 3.6
      cases per 100 person-years). Nevertheless, this observation remains mostly
      significant for patients with PMF, as those with PEV/PVT-MF have already
      significantly inferior prognosis with platelets <100 * 109 /L.

PMID- 29226427
TI  - Case Report: Treatment of light-chain amyloidosis with daratumumab monotherapy in
      two patients.
AB  - Immunoglobulin light-chain amyloidosis (AL) affects multiple organs, most
      prominently the kidney and the heart. Renal and cardiac impairment are both
      associated with poor prognosis and most patients die as a consequence of renal or
      cardiac failure. Monoclonal antibodies such as daratumumab (human IgG1 anti-CD38)
      and elotuzumab (anti-SLAMF7) have shown promising efficacy for the treatment of
      relapsed and refractory multiple myeloma. In this case report we show 2 patients
      with severe AL, one with severe heart failure and one with heart and renal
      failure, undergoing treatment with daratumumab. Both patients showed a rapid
      decrease in FLC in response to daratumumab infusions, with few associated adverse
      events. Using therapeutic CD38 antibodies as a front-line treatment for AL could
      induce rapid responses while maintaining a tolerable safety profile in these
      ultra-fragile patients.

PMID- 29226428
TI  - Predictive value of 18 F-FDG PET/CT scanning in combination with clinical
      parameters in patients with newly diagnosed multiple myeloma.
AB  - OBJECTIVE: To evaluate the association of 18 F-2'-deoxy 2'-fluorodeoxyglucose (18
      F-FDG) PET/CT with clinical parameters in predicting patients with newly
      diagnosed multiple myeloma (MM). METHODS: A total of 120 MM patients undergoing
      18 F-FDG PET/CT scanning were analyzed in a retrospective cohort study. RESULTS:
      Based on multivariate analysis, beta2M, LDH, number of focal lesions (FLs), and
      SUVmax were significantly correlated with OS. These 4 variables were used to
      construct a new staging system (NSS) based on the number of risk factors. NSS
      provided a better discrimination of risk between stages III and II than
      International staging system (ISS) (P < .001 vs P = .086). For OS, there was no
      significant difference among risk groups in Durie-Salmon (DS) stage (P > .05).
      Based on Spearman correlation analysis, the presence of lesions in appendicular
      skeleton, number of FLs, and SUVmax appeared to indicate advanced stage of MM.
      ROC curves which showed the combination of beta2M with calcium got a specificity
      of 96.3% for lesions in appendicular skeleton, and LDH alone had 100% specificity
      in predicting the number of FLs, although the sensitivity was only 50%.
      CONCLUSIONS: 18 F-FDG PET/CT in combination with clinical parameters provided an
      accurate and simple method for risk stratification of patients with newly
      diagnosed MM.

PMID- 29226429
TI  - Morphological variations of the human ejaculatory ducts in relation to the
      prostatic urethra.
AB  - Loss of ejaculation can follow transurethral resection of the prostate (TURP).
      Periverumontanal prostate tissue is preserved in ejaculation-preserving TURP (ep
      TURP). Knowledge of ejaculatory duct anatomy in relation to the prostatic urethra
      can help in ep-TURP. This was evaluated in cross-sections of the prostate using a
      3 D model to determine a safe zone for resecting the prostate in ep-TURP. A 3 D
      reconstruction of the ejaculatory ducts was developed on the basis of six
      prostate gland cross-sections. The measurements obtained from the 3 D model were
      standardized according to the maximum width of the prostate. Simple linear
      regressions were used to predict the relationships of the ejaculatory ducts. The
      maximum widths of the prostates ranged from 22.60 to 52.10 mm. The ejaculatory
      ducts entered the prostate with a concavity directed posterolaterally. They then
      proceeded toward the seminal colliculus in a fairly straight course, and from
      that point they angulated anteromedially. As they opened into the prostatic
      urethra they diverged. Significant regression models predicted the relationships
      of the ejaculatory ducts to the prostatic urethra based on the sizes of the
      prostates. The 3 D anatomy of ejaculatory ducts can be predicted on the basis of
      prostate width. The ejaculatory ducts can be preserved with 95% accuracy if a
      block of tissue 7.5 mm from the midline on either side of the seminal colliculus
      is preserved, up to 10 mm proximal to the level of the seminal colliculus, during
      TURP. Clin. Anat. 31:456-461, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226430
TI  - 3DTEE imaging of a descending aorta floating thrombus in a patient with
      calciphylaxis.
AB  - We present a case of a 68-year-old man with calciphylaxis, who was found to have
      a floating thrombus in the descending aorta on a transesophageal echocardiogram.
      The use of 3D echocardiography demonstrated nicely the free motion of the
      thrombus, emerging from an atherosclerotic plaque in the descending aorta.
      Anticoagulation was started for thromboembolism prevention.

PMID- 29226431
TI  - The effect of dialysis type on left atrial functions in patients with end-stage
      renal failure: A propensity score-matched analysis.
AB  - INTRODUCTION: Despite the widespread use of both hemodialysis (HD) and peritoneal
      dialysis (PD), there is no study comparing the effects of these dialysis methods
      on the left atrial (LA) volume and functions. In this study, we investigated the
      impact of different dialysis methods on the LA volume and function in the
      patients exposed to chronic pressure overload and volume overload. METHOD: This
      study was carried out on the patients who received dialysis treatment at our
      healthcare center between March, 2015 and January, 2016. Twenty-eight patients
      receiving hemodialysis (HD) treatment and 24 patients under PD treatment were
      enrolled into the study. Patients were divided into 2 groups according to the
      dialysis therapy, and the atrial volumetric and mechanical functions were
      investigated. RESULTS: As the basal demographical characteristics of patients in
      the PD and HD groups were significantly different, 44 patients matched on a 1:1
      basis were taken for final analysis (22 HD, 22 PD, and the average age of 42.4 +/
      4.8; 73% was male). After propensity score matching analysis, it was determined
      that left atrial volume index (LAVi) was higher in the HD group while peak LA
      strain and LA contraction strain were higher in the PD group. Additionally, both
      strain parameters showed a good negative correlation with LAVi. CONCLUSION: We
      demonstrated that the left atrial structure and functions were better in the PD
      group suggesting that PD may be a relatively better option for the preservation
      and maintenance of the left atrial functions as compared to HD.

PMID- 29226432
TI  - Multi-Functional Peptide-MicroRNA Nanocomplex for Targeted MicroRNA Delivery and
      Function Imaging.
AB  - Targeted delivery of microRNA (miRNA) mimics into specific cells/tissues and real
      time monitoring on the biological function of delivered miRNA mimics at molecular
      level represent two major challenges in the development of miRNA-based
      therapeutics. Here we report a highly efficient method to address these two
      challenges simultaneously by using the self-assembled nanocomplex formed by miRNA
      mimics with a multi-functional peptide conjugate. Using the nanocomplex formed by
      tumor-suppressive miR-34a and the multi-functional peptide conjugate FA-R9-FPcas3
      , we demonstrated the highly efficient and target-selective delivery of miR-34a
      into HeLa cells and tumors. With the activatable fluorescence probe integrated in
      the peptide conjugate FA-R9-FPcas3 , the intracellular function of miR-34a
      delivered by the nanocomplex to upregulate active Caspase-3 was imaged in real
      time. The nanocomplex also showed significant therapeutic effects to induce
      apoptosis in HeLa cells and to suppress tumor growth upon tail vein injection
      into living mice bearing subcutaneous HeLa tumors.

PMID- 29226433
TI  - Interlocked Photo-degradable Macrocycles Allow One-Off Photo-triggerable Gelation
      of Organo- and Hydrogelators.
AB  - [2]Rotaxanes displaying one-off photo-triggerable gelation properties have been
      synthesized through the "clipping" of photo-degradable macrocycles around the
      amide or urea functionalities of organo- and hydrogelators. Irradiation with UV
      light cleaved the photo-labile macrocyclic components from the [2]rotaxanes,
      resulting in the free gelators being released into solution and, thereafter,
      forming gels. When the rate of gelation was sufficiently rapid, selective
      gelation of specific regions of the solution-and, indeed, photo-patterning of the
      solution-was possible.

PMID- 29226434
TI  - Protein identification in imaging mass spectrometry through spatially targeted
      liquid micro-extractions.
AB  - RATIONALE: Liquid extraction surface analysis (LESA) can be used to generate
      spatially directed protein identifications in an imaging mass spectrometry (IMS)
      workflow. This approach involves the use of robotic micro-extractions coupled to
      online liquid chromatography (LC). We have characterized the extraction
      efficiency of this method as well as its ability to identify proteins from a
      matrix assisted laser/desorption ionization (MALDI) IMS experiment. METHODS:
      Proteins and peptides were extracted from transverse sections of a rat brain and
      sagittal sections of a mouse pup using liquid surface extractions. Extracts were
      either analyzed by online LC coupled to a high mass resolution Fourier transform
      ion cyclotron resonance (FTICR) mass spectrometer or collected offline and
      analyzed by traditional LC/MS methods. Identifications were made using both top
      down and bottom-up methodologies. MALDI images were acquired on a 15T FTICR mass
      spectrometer at 125 MUm spatial resolution. RESULTS: Robotic liquid surface
      extractions are reproducible across various tissue types, providing significantly
      improved spatial resolution, with respect to extractions, while still allowing
      for a robust number of protein identifications. A single 2-MUL extract can
      provide identification of over 14,000 peptides with little sample preparation,
      increasing throughput for spatially targeted workflows. Surface extractions from
      tissue were coupled directly to LC to gather spatially relevant proteomics data.
      CONCLUSIONS: Robotic liquid surface extractions can be used to interrogate
      discrete regions of tissue to provide protein identifications with high
      throughput, accuracy, and robustness. The direct coupling of tissue surface
      extractions and LC offers a new and effective approach to provide spatial
      proteomics data in an imaging experiment.

PMID- 29226435
TI  - High-Capacity and High-Rate Discharging of a Coenzyme Q10 -Catalyzed Li-O2
      Battery.
AB  - Discharging of the aprotic Li-O2 battery relies on O2 reduction to insulating
      solid Li2 O2 , which can either deposit as thin films on the cathode surface or
      precipitate as large particles in the electrolyte solution. Toward realizing Li
      O2 batteries with high capacity and high rate capability, it is crucially
      important to discharge Li2 O2 in the electrolyte solution rather than on the
      cathode surface. Here, a soluble electrocatalyst of coenzyme Q10 (CoQ10 ) that
      can efficaciously drive solution phase formation of Li2 O2 in current benchmark
      ether-based Li-O2 batteries is reported, which would otherwise lead to Li2 O2
      surface-film growth and premature cell death. In the range of current densities
      of 0.1-0.5 mA cm-2areal , the CoQ10 -catalyzed Li-O2 battery can deliver a
      discharge capacity that is ~40-100 times what the pristine Li-O2 battery could
      achieve. The drastically enhanced electrochemical performance is attributed to
      the CoQ10 that not only efficiently mediates the electron transfer from the
      cathode to dissolve O2 but also strongly interacts with the newly formed Li2 O2
      in solution retarding its precipitation on the cathode surface. The mediated
      oxygen reduction reaction and the bonding mechanism between CoQ10 and Li2 O2 are
      understood with density functional theory calculations.

PMID- 29226436
TI  - Elaborate ultrastructure of the Hirudo (Annelida: Hirudinae) cocoon surface.
AB  - Species of medicinal leeches (Hirudo medicinalis, H. verbana, and H. sulukii)
      secrete hard-shelled cocoons. When initially deposited, a cocoon is surrounded by
      a foam. Over a short time, the foam is transformed into a three-dimensional
      structure. We show here that this peripheral structure likely forms by the
      solidification and dehydration of a moderately viscous, proteinaceous substance
      that surrounds bubbles of various sizes. The resulting matrix-like structure
      comprises a network of curved branches juxtaposed at ~120 degrees  and taper in
      width as a function of distance from the outer cocoon wall. The material is
      proteinaceous, and traps environmental material in its composition, especially
      silicon. The geometry of compartments and abundance of silicon on branch surfaces
      suggest a mechanism for trapping water to prevent desiccation in a terrestrial
      environment.

PMID- 29226437
TI  - On Effective Graphic Communication of Health Inequality: Considerations for
      Health Policy Researchers.
AB  - : Policy Points: Effective graphs can be a powerful tool in communicating health
      inequality. The choice of graphs is often based on preferences and familiarity
      rather than science. According to the literature on graph perception, effective
      graphs allow human brains to decode visual cues easily. Dot charts are easier to
      decode than bar charts, and thus they are more effective. Dot charts are a
      flexible and versatile way to display information about health inequality.
      Consistent with the health risk communication literature, the captions
      accompanying health inequality graphs should provide a numerical, explicitly
      calculated description of health inequality, expressed in absolute and relative
      terms, from carefully thought-out perspectives. CONTEXT: Graphs are an essential
      tool for communicating health inequality, a key health policy concern. The choice
      of graphs is often driven by personal preferences and familiarity. Our article is
      aimed at health policy researchers developing health inequality graphs for policy
      and scientific audiences and seeks to (1) raise awareness of the effective use of
      graphs in communicating health inequality; (2) advocate for a particular type of
      graph (ie, dot charts) to depict health inequality; and (3) suggest key
      considerations for the captions accompanying health inequality graphs. METHODS:
      Using composite review methods, we selected the prevailing recommendations for
      improving graphs in scientific reporting. To find the origins of these
      recommendations, we reviewed the literature on graph perception and then applied
      what we learned to the context of health inequality. In addition, drawing from
      the numeracy literature in health risk communication, we examined numeric and
      verbal formats to explain health inequality graphs. FINDINGS: Many disciplines
      offer commonsense recommendations for visually presenting quantitative data. The
      literature on graph perception, which defines effective graphs as those allowing
      the easy decoding of visual cues in human brains, shows that with their more
      accurate and easier-to-decode visual cues, dot charts are more effective than bar
      charts. Dot charts can flexibly present a large amount of information in limited
      space. They also can easily accommodate typical health inequality information to
      describe a health variable (eg, life expectancy) by an inequality domain (eg,
      income) with domain groups (eg, poor and rich) in a population (eg, Canada) over
      time periods (eg, 2010 and 2017). The numeracy literature suggests that a health
      inequality graph's caption should provide a numerical, explicitly calculated
      description of health inequality expressed in absolute and relative terms, from
      carefully thought-out perspectives. CONCLUSIONS: Given the ubiquity of graphs,
      the health inequality field should learn from the vibrant multidisciplinary
      literature how to construct effective graphic communications, especially by
      considering to use dot charts.

PMID- 29226438
TI  - The "Great" Generation and a Not-So-Great Health System.

PMID- 29226439
TI  - On the Production of Useful Knowledge.

PMID- 29226441
TI  - Reforming American Medical Education.

PMID- 29226442
TI  - Common Ground on Responsibility for Health.

PMID- 29226445
TI  - Topsy-Turvy.

PMID- 29226443
TI  - Lessons From Analyzing the Medical Costs of Civilian Terror Victims: Planning
      Resources Allocation for a New Era of Confrontations.
AB  - : Policy Points: Across the globe, the threat from terrorist attacks is rising,
      which requires a careful assessment of long-term medical support. We found 3
      major sources of costs: hospital expenditures, mental health services dedicated
      to acute stress reactions, and ambulatory follow-up. During the first year, most
      of the costs were related to hospitalization and support for stress relief.
      During the second year, ambulatory and rehabilitation costs continued to grow.
      Public health specialists should consider these major components of costs and
      their evolution over time to properly advise the medical and social authorities
      on allocating resources for the medical and nonmedical support of civilian
      casualties resulting from war or terror. CONTEXT: Across the globe, the threat
      from terrorist attacks is rising, which requires a careful assessment of long
      term medical support. Based on an 18-month follow-up of the Israeli civilian
      population following the 2014 war in Gaza, we describe and analyze the medical
      costs associated with rocket attacks and review the demography of the victims who
      filed claims for disability compensation. We then propose practical lessons to
      help health care authorities prepare for future confrontations. METHOD: Using the
      National Insurance Institute of Israel's (NII) database, we conducted descriptive
      and comparative analyses using statistical tests (Fisher's Exact Test, chi-square
      test, and students' t-tests). The costs were updated until March 30, 2016, and
      are presented in US dollars. We included only civilian expenses in our analysis.
      FINDINGS: We identified 5,189 victims, 3,236 of whom presented with acute stress
      reactions during the conflict. Eighteen months after the conflict, the victims'
      total medical costs reached $4.4 million. The NII reimbursed $2,541,053 for
      associated medical costs and $1,921,792 for associated mental health costs. A
      total of 709 victims filed claims with the NII for further support, including
      rehabilitation, medical devices, and disability pensions. CONCLUSION: We found 3
      major sources of costs: hospital expenditures, mental health services dedicated
      to acute stress reactions, and ambulatory follow-up. During the first year, most
      of the costs were related to hospitalization and support for stress relief.
      During the second year, ambulatory and rehabilitation costs continued to grow.
      Public health specialists should consider these major components of costs and
      their evolution over time to properly advise the medical and social authorities
      on allocating resources for the medical and nonmedical support of civilian
      casualties resulting from war or terror.

PMID- 29226446
TI  - Stewing Over Chemical Soups.

PMID- 29226447
TI  - The Politics of Medicaid: Most Americans Are Connected to the Program, Support
      Its Expansion, and Do Not View It as Stigmatizing.
AB  - : Policy Points: More than half of Americans are connected to the Medicaid
      program-either through their own coverage or that of a family member or close
      friend-and are significantly more likely to view Medicaid as important and to
      support increases in spending, even among conservatives. This finding helps
      explain why Affordable Care Act repeal efforts faced (and will continue to face)
      strong public backlash. Policymakers should be aware that although renaming
      programs within Medicaid may have increased enrollment take-up, this
      destigmatization effort might have also increased program confusion and reduced
      support for Medicaid even among enrollees who say the program is important to
      them. CONTEXT: Since the 1980s, Medicaid enrollment has expanded so dramatically
      that by 2015 two-thirds of Americans had some connection to the program in which
      either they themselves, a family member, or a close friend is currently or was
      previously enrolled. METHODS: Utilizing a nationally representative survey-the
      Kaiser Family Foundation Poll: Medicare and Medicaid at 50 (n = 1,849)-and
      employing ordinal and logistic regression analyses, our study examines 3
      questions: (1) are individuals with a connection to Medicaid more likely to view
      the program as important, (2) are they more likely to support an increase in
      Medicaid spending, and (3) are they more likely to support adoption of the
      Medicaid expansion offered under the Affordable Care Act? For each of these
      questions we examine whether partisanship and views of stigma also impact support
      for Medicaid and, if so, whether these factors overwhelm the impact of connection
      to the program. FINDINGS: Controlling for the strong effect of partisanship,
      people with any connection to the Medicaid program are more likely to view the
      program as important than those with no connection. However, when it comes to
      increasing spending or expanding the program, the type of connection to the
      program matters. In particular, adults with current and previous Medicaid
      coverage and those with a family member or close friend with Medicaid coverage
      are more likely to support increases in spending and the Medicaid expansion; but,
      those connected to Medicaid only through coverage of a child are no more likely
      to support Medicaid than those with no connection. CONCLUSIONS: Future research
      should probe more deeply into whether people with different types of connection
      to Medicaid view the program differently, and, if so, how and why. Moreover,
      future research should also explore whether state-level attempts to destigmatize
      Medicaid by renaming the program also serves to reduce knowledge and support for
      Medicaid.

PMID- 29226448
TI  - Better Measurement for Performance Improvement in Low- and Middle-Income
      Countries: The Primary Health Care Performance Initiative (PHCPI) Experience of
      Conceptual Framework Development and Indicator Selection.
AB  - : Policy Points: Strengthening accountability through better measurement and
      reporting is vital to ensure progress in improving quality primary health care
      (PHC) systems and achieving universal health coverage (UHC). The Primary Health
      Care Performance Initiative (PHCPI) provides national decision makers and global
      stakeholders with opportunities to benchmark and accelerate performance
      improvement through better performance measurement. Results from the initial PHC
      performance assessments in low- and middle-income countries (LMICs) are helping
      guide PHC reforms and investments and improve the PHCPI's instruments and
      indicators. Findings from future assessment activities will further amplify cross
      country comparisons and peer learning to improve PHC. New indicators and sources
      of data are needed to better understand PHC system performance in LMICs. CONTEXT:
      The Primary Health Care Performance Initiative (PHCPI), a collaboration between
      the Bill and Melinda Gates Foundation, The World Bank, and the World Health
      Organization, in partnership with Ariadne Labs and Results for Development, was
      launched in 2015 with the aim of catalyzing improvements in primary health care
      (PHC) systems in 135 low- and middle-income countries (LMICs), in order to
      accelerate progress toward universal health coverage. Through more comprehensive
      and actionable measurement of quality PHC, the PHCPI stimulates peer learning
      among LMICs and informs decision makers to guide PHC investments and reforms.
      Instruments for performance assessment and improvement are in development; to
      date, a conceptual framework and 2 sets of performance indicators have been
      released. METHODS: The PHCPI team developed the conceptual framework through
      literature reviews and consultations with an advisory committee of international
      experts. We generated 2 sets of performance indicators selected from a literature
      review of relevant indicators, cross-referenced against indicators available from
      international sources, and evaluated through 2 separate modified Delphi
      processes, consisting of online surveys and in-person facilitated discussions
      with experts. FINDINGS: The PHCPI conceptual framework builds on the current
      understanding of PHC system performance through an expanded emphasis on the role
      of service delivery. The first set of performance indicators, 36 Vital Signs,
      facilitates comparisons across countries and over time. The second set, 56
      Diagnostic Indicators, elucidates underlying drivers of performance. Key
      challenges include a lack of available data for several indicators and a lack of
      validated indicators for important dimensions of quality PHC. CONCLUSIONS: The
      availability of data is critical to assessing PHC performance, particularly
      patient experience and quality of care. The PHCPI will continue to develop and
      test additional performance assessment instruments, including composite indices
      and national performance dashboards. Through country engagement, the PHCPI will
      further refine its instruments and engage with governments to better design and
      finance primary health care reforms.

PMID- 29226449
TI  - CMS, Demonstration Projects, and the Future of Value-Based Payments.

PMID- 29226450
TI  - Barriers to Care Among Transgender and Gender Nonconforming Adults.
AB  - : Policy Points: Transgender and gender nonconforming (GNC) adults may experience
      barriers to care for a variety of reasons, including discrimination and lack of
      awareness by providers in health care settings. In our analysis of a large,
      population-based sample, we found transgender and GNC adults were more likely to
      be uninsured and have unmet health care needs, and were less likely to have
      routine care, compared to cisgender (nontransgender) women. Our findings varied
      by gender identity. More research is needed on transgender and GNC populations,
      including on how public policy and provider awareness affects health care access
      and health outcomes differentially by gender identity. CONTEXT: Very little
      population-based research has examined health and access to care among
      transgender populations. This study compared barriers to care between cisgender,
      transgender, and gender nonconforming (GNC) adults using data from a large,
      multistate sample. METHODS: We used data from the 2014-2015 Behavioral Risk
      Factor Surveillance System to estimate the prevalence of having no health
      insurance, unmet medical care needs due to cost, no routine checkup, and no usual
      source of care for cisgender women (n = 183,370), cisgender men (n = 131,080),
      transgender women (n = 724), transgender men (n = 449), and GNC adults (n = 270).
      Logistic regression models were used to estimate odds ratios (OR) and 95%
      confidence intervals (CI) for each barrier to care while adjusting for
      sociodemographic characteristics. FINDINGS: Transgender and GNC adults were more
      likely to be nonwhite, sexual minority, and socioeconomically disadvantaged
      compared to cisgender adults. After controlling for sociodemographic
      characteristics, transgender women were more likely to have no health insurance
      (OR = 1.60; 95% CI = 1.07-2.40) compared to cisgender women; transgender men were
      more likely to have no health insurance (OR = 2.02; 95% CI = 1.25-3.25) and no
      usual source of care (OR = 1.84; 95% CI = 1.18-2.88); and GNC adults were more
      likely to have unmet medical care needs due to cost (OR = 1.93; 95% CI = 1.02
      3.67) and no routine checkup in the prior year (OR = 2.41; 95% CI = 1.41-4.12).
      CONCLUSIONS: Transgender and GNC adults face barriers to health care that may be
      due to a variety of reasons, including discrimination in health care, health
      insurance policies, employment, and public policy or lack of awareness among
      health care providers on transgender-related health issues.

PMID- 29226451
TI  - Pictorial essay of ultrasound-reconstructed coronal plane images of the uterus in
      different uterine pathologies.
AB  - Imaging in the major planes (horizontal, coronal, and sagittal) of the uterus is
      important for determining anatomy and allowing the findings to be standardized,
      and for evaluating and diagnosing different pathological conditions in clinical
      practice. Examination of the coronal plane is an important step in identifying
      uterine pathologies and their relationships to the endometrial canal. Three
      dimensional (3D) ultrasound reveals the normal anatomy better and improves the
      depiction of abnormal anatomy, as the coronal plane of the uterus can easily be
      obtained using 3D reconstruction techniques. Our pictorial essay demonstrates
      that adding 3D ultrasound to a routine gynecological workup can be beneficial for
      clinicians, enabling a precise diagnosis to be made. In addition, the volumes
      obtained and stored by 3D ultrasound can allow students or residents to become
      more familiar with normal and abnormal pelvic structures. Clin. Anat. 31:373-379,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226452
TI  - Clinical characteristics of Japanese patients with psoriatic arthritis:
      Comparison with East Asian countries.
AB  - To determine the characteristics and current status of Japanese patients with
      psoriatic arthritis, the Japanese Society for Psoriasis Research have started to
      conduct retrospective questionnaire surveys. The results collected from over a
      thousand patients with psoriatic arthritis have revealed several characteristics.
      The newly visited psoriatic arthritis patients accounted for approximately 10% of
      all new psoriatic patients who visited the dermatology department in many
      referral centers. The prevalence was nearly 15% of psoriatic patients, which was
      similar to a recent rheumatology and dermatology study in Japan with a large
      cohort. There was a male predominance. The mean age of onset for cutaneous
      psoriasis was in the late 30s, while that of arthritis was in the late 40s. If we
      compare the precedence of cutaneous psoriasis versus arthritis, the psoriasis
      precedent group accounted for nearly 75%, while arthritis accounted for 5% of
      cases. The mean duration in patients who developed psoriasis prior to arthritis
      was over 10 years, while that in patients preceded by arthritis was less than 5
      years. According to the Moll and Wright criteria, polyarthritis type was most
      common, followed by distal interphalangeal type and oligoarthritis type.
      Biologics were used in over 50% of psoriatic arthritis patients, and TNF
      inhibitors were currently used in approximately 70% among biologics. Switching to
      other biologics or discontinuance was seen in 15%. This review shows the current
      status of psoriatic arthritis in Japan, as well as a comparison of the prevalence
      among East Asian countries.

PMID- 29226453
TI  - Silver(I)-Mediated Base Pairs in DNA Sequences Containing 7
      Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson-Crick Base
      Pairs.
AB  - DNA sequences comprising noncanonical 7-deazaguanine (7C G) and canonical
      cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as
      well as silver(I)-mediated base pairs by coordination to central silver(I) ions.
      Duplexes I and II containing 7C G and C have been synthesized and characterized.
      The incorporation of silver(I) ions into these duplexes has been studied by means
      of temperature-dependent UV spectroscopy, circular dichroism, and DFT
      calculations. The results suggest the formation of DNA molecules comprising
      contiguous metallated 7C G-AgI -C Watson-Crick base pairs that preserve the
      original B-type conformation. Furthermore, additional studies performed on duplex
      III indicated that, in the presence of AgI ions, 7C G-C and 7C A-T Watson-Crick
      base pairs (7C A, 7-deazadenine; T, thymine) can be converted to metallated 7C G
      AgI -C and 7C A-AgI -T base pairs inside the same DNA molecule whilst maintaining
      its initial double helix conformation. These findings are very important for the
      development of customized silver-DNA nanostructures based on a Watson-Crick
      complementarity pattern.

PMID- 29226454
TI  - A New Member of Electrocatalysts Based on Nickel Metaphosphate Nanocrystals for
      Efficient Water Oxidation.
AB  - High-performance electrocatalysts are desired for electrochemical energy
      conversion, especially in the field of water splitting. Here, a new member of
      phosphate electrocatalysts, nickel metaphosphate (Ni2 P4 O12 ) nanocrystals, is
      reported, exhibiting low overpotential of 270 mV to generate the current density
      of 10 mA cm-2 and a superior catalytic durability of 100 h. It is worth noting
      that Ni2 P4 O12 electrocatalyst has remarkable oxygen evolution performance
      operating in basic media. Further experimental and theoretical analyses
      demonstrate that N dopant boosts the catalytic performance of Ni2 P4 O12 due to
      optimizing the surface electronic structure for better charge transfer and
      decreasing the adsorption energy for the oxygenic intermediates.

PMID- 29226455
TI  - Perceptions of oral health among older Cambodians and their caregivers: A
      qualitative study.
AB  - OBJECTIVE: Older adults (those above the age of 60) are an emerging demographic
      in Cambodia, and very little is understood about their oral health experiences,
      needs, perceptions and behaviours. The aim of this study was to explore the oral
      health experiences, practices and perceptions of a convenience sample of a small
      but diverse group of older adults in Cambodia. METHOD: A cross-sectional
      qualitative study in which focus group interviews were conducted by 5 trained
      senior Cambodian dental students. A convenience sample of 56 older adults and
      caregivers was recruited across urban, semi-urban and rural locations. Focus
      group conversations were recorded, transcribed and analysed thematically.
      RESULTS: The themes that emerged were around low expectations for both general
      health and oral health. A communal responsibility for health was expressed, and
      both money and transport were identified as key barriers to accessing care.
      Participants recognised that they had oral health problems, and acknowledged the
      impact of poor oral function on health and nutrition. CONCLUSION: This study is
      an important first step in better understanding the oral health experiences and
      perceptions of older people in Cambodia. Participants described the impacts of
      poor oral health as being important, even when compared with other general health
      conditions.

PMID- 29226456
TI  - Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a
      receptor for advanced glycation end-products-dependent manner.
AB  - Oral squamous cell carcinoma (OSCC) affects approximately 30,000 people and is
      associated with tobacco use. Little is known about the mechanistic effects of
      second-hand smoke in the development of OSSC. The receptor for advanced glycation
      end-products (RAGE) is a surface receptor that is upregulated by second-hand
      smoke and inhibited by semi-synthetic glycosaminoglycan ethers (SAGEs). Our
      objective was to determine the role of RAGE during cigarette smoke extract
      induced cellular responses and to use SAGEs as a modulating factor of Ca9-22 OSCC
      cell invasion. Ca9-22 cells were cultured in the presence or absence of cigarette
      smoke extract and SAGEs. Cell invasion was determined and cells were lysed for
      western blot analysis. Ras and nuclear factor of kappa light polypeptide gene
      enhancer in B-cells (NF-kappaB) activation were determined. Treatment of cells
      with cigarette smoke extract resulted in: (i) increased invasion of OSCC; (ii)
      increased RAGE expression; (iii) inhibition of cigarette smoke extract-induced
      OSCC cell invasion by SAGEs; (iv) increased Ras, increased AKT and NF-kappaB
      activation, and downregulation by SAGEs; and (v) increased expression of matrix
      metalloproteinases (MMPs) 2, 9, and 14, and downregulation by SAGEs. We conclude
      that cigarette smoke extract increases invasion of OSCC cells in a RAGE-dependent
      manner. Inhibition of RAGE decreases the levels of its signaling molecules, which
      results in blocking the cigarette smoke extract-induced invasion.

PMID- 29226458
TI  - Communicating risk in dementia care: Survey of health and social care
      professionals.
AB  - Supporting people to live at home in line with community care policies requires
      increasing attention to assessing, communicating and managing risks. There is a
      challenge in supporting client choices that include risk-taking while
      demonstrating professional accountability. Risk communication becomes
      increasingly important with the need to engage clients and families in meaningful
      shared decision-making. This presents particular challenges in dementia services.
      This survey of risk communication in dementia care was administered to all health
      and social care professionals in community dementia services in Northern Ireland:
      June-September 2016. Of 270 professionals, 70 questionnaires were fully
      completed, with 55 partial completions. Scores on the Berlin Numeracy Test plus
      Schwartz items was low-moderate (mean 2.79 out of 7). This study did not find a
      significant association between numeracy and accurate perceptions of risk
      likelihoods in practice-based scenarios. Although 86% reported using numeric
      information in practice (mostly from assessment tools), respondents rarely
      communicated themselves using numbers. As in other domains, participants'
      responses were widely variable on numeric estimates of verbal terms for
      likelihood. In relation to medication side effects, few participants provided
      responses that were concordant with those in the guidance of the European Union.
      The risks most commonly encountered in practice were (in rank order): falls,
      depression, poor personal hygiene, medicines mismanagement, leaving home
      unsupervised, financial mismanagement, malnutrition, swallowing difficulties,
      abuse from others, risks to others, home appliance accidents and refusing
      equipment. Respondents generally overestimated the likelihood of serious harmful
      events by approximately 10-fold (having a missing person's report filed with the
      police; having a fall resulting in hospitalisation) and by approximately double
      (being involved in a car accident; causing a home fire), and with wide variation
      between respondents. There is potential in icon arrays for communicating risks.
      Risk literacy among dementia care practitioners needs to be developed.

PMID- 29226457
TI  - Investigation of in vitro measurable sperm attributes and their influence on
      electroejaculated bull semen with a fixed-time artificial insemination protocol
      in Australian Bos indicus cattle.
AB  - Increasing use of fixed-time artificial insemination (FTAI) in beef cattle
      production has presented an opportunity for the use of fresh or chilled semen as
      an alternative to standard cryopreserved semen. The objective of this study was
      to examine in vitro sperm function and pregnancy rate of electroejaculated semen,
      chilled and stored for 48 hr, compared to conventionally cryopreserved semen with
      an optimized FTAI protocol in Brahman cattle. Semen from three Brahman bulls was
      collected, and aliquots were extended in either chilled (at 5 degrees C) or
      frozen (LN2 ) in a Tris-egg yolk extender base with 2.4% or 7.0% glycerol,
      respectively. Semen samples were assessed 48 hr after collection or post-thaw and
      warming, for sperm motility, in vitro sperm function and fertilizing ability, and
      used in a FTAI programme. The overall pregnancy rates was significantly different
      (p < .01) after FTAI with frozen (n = 173; 53.2%) and chilled semen (n = 174;
      31.6%). In contrast, the in vitro sperm assessment showed that the chilled semen
      had significantly faster motility (p < .05), a higher proportion of progressively
      motile spermatozoa (p < .05), with significantly higher proportions of acrosome
      intact, viable spermatozoa (p < .01). This study showed that reasonable pregnancy
      rates in Brahman cattle can be achieved using FTAI with chilled semen collected
      using electroejaculation and stored for up to 48 hr. However, improvements in
      semen extenders are required in consideration of semen collection method to
      improve the longevity of sperm fertilizing ability to significantly increase FTAI
      output using chilled storage of bull semen.

PMID- 29226459
TI  - A Lithography-Free and Field-Programmable Photonic Metacanvas.
AB  - The unique correspondence between mathematical operators and photonic elements in
      wave optics enables quantitative analysis of light manipulation with individual
      optical devices. Phase-transition materials are able to provide real-time
      reconfigurability of these devices, which would create new optical
      functionalities via (re)compilation of photonic operators, as those achieved in
      other fields such as field-programmable gate arrays (FPGA). Here, by exploiting
      the hysteretic phase transition of vanadium dioxide, an all-solid, rewritable
      metacanvas on which nearly arbitrary photonic devices can be rapidly and
      repeatedly written and erased is presented. The writing is performed with a low
      power laser and the entire process stays below 90  degrees C. Using the
      metacanvas, dynamic manipulation of optical waves is demonstrated for light
      propagation, polarization, and reconstruction. The metacanvas supports physical
      (re)compilation of photonic operators akin to that of FPGA, opening up
      possibilities where photonic elements can be field programmed to deliver complex,
      system-level functionalities.

PMID- 29226460
TI  - CT pulmonary angiogram for assessing the treatment outcome of acute pulmonary
      embolism.
AB  - OBJECTIVE: To discuss the value of CT pulmonary angiogram (CTPA) for assessing
      the treatment outcome of acute pulmonary embolism (APE). MATERIALS AND METHODS:
      CT pulmonary angiogram data and other clinical data were collected for 28 cases
      diagnosed as APE and analyzed retrospectively. The number and positions of emboli
      in the pulmonary artery, pulmonary artery obstruction index, right
      ventricular/left ventricular diameter ratio, main pulmonary artery/ascending
      aorta diameter ratio and blood oxygen saturation, and pulmonary arterial pressure
      were compared before and after treatment. RESULTS: Of 28 cases, emboli in the
      pulmonary artery completely or partially disappeared in 16 and 12 cases,
      respectively. CPTA indicated that the pulmonary arterial pressure decreased
      dramatically and the blood oxygen saturation increased after treatment in 26
      cases. There were significant differences in the number and positions of
      pulmonary emboli and in pulmonary artery obstruction index before and after
      treatment in 28 cases (P < .05). However, no significant differences were found
      in the right ventricular/left ventricular diameter ratio or main pulmonary
      artery/ascending aorta diameter ratio (P > .05). CONCLUSION: CT pulmonary
      angiogram proved reliable for assessing the treatment efficacy of APE, providing
      more clinical information on the patients' status.

PMID- 29226461
TI  - Long non-coding PANDAR as a novel biomarker in human cancer: A systematic review.
AB  - OBJECTIVES: Long non-coding RNAs (lncRNAs) are characterized as a group of RNAs
      that more than 200 nucleotides in length and have no protein-coding function.
      More and more evidences provided that lncRNAs serve as key molecules in the
      development of cancer. Deregulation of lncRNAs functions as either oncogenes or
      tumour suppressor genes in various diseases. Recently, increasing studies about
      PANDAR in cancer progression were reported. In our review, we will focus on the
      current research on the character of PANDAR include the clinical management,
      tumour progression and molecular mechanisms in human cancers. MATERIALS AND
      METHODS: We summarize and analyze current studies concerning the biological
      functions and mechanisms of lncRNA PANDA in tumour development. The related
      studies were obtained through a systematic search of Pubmed. RESULTS: PANDAR was
      a well-characterized oncogenic lncRNA and widely overexpressed in many tumours.
      PANDAR is upregulated in many types of cancer, including colorectal cancer, lung
      cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer
      and other cancers. Upregulation of PANDAR was significantly associated with
      advanced tumour weights, TNM stage and overall survival. Furthermore, repressed
      of PANDAR would restrain proliferation, migration and invasion. CONCLUSION:
      PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment.

PMID- 29226462
TI  - Spontaneous death of rat chloroleukaemia cells induced by an endogenous growth
      inhibitor.
AB  - OBJECTIVES: When rat chloroleukaemia (CHL) cells are grown undisturbed in a
      confined space, a genomic long interspersed nuclear element (LINE) is
      transcriptionally activated at a relatively low population density, followed by
      the retrotransposition of LINE and population death. This death programme is
      fundamentally different from conventional cell death pathways. MATERIALS AND
      METHODS: This work is essentially based on the re-analysis of relevant, old
      experimental data. Elemental analysis of a highly purified, long-stored inhibitor
      sample was performed. Genomic sequence searches were performed using the basic
      local alignment search tool (BLAST). RESULTS: This death programme is initiated
      by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost
      certainly identical to the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, shown to be a
      cell line-specific inhibitor of normal granulocytic cells. The inhibitor is
      derived from a highly conserved short open reading frame in mammalian genomes.
      CONCLUSIONS: Although spontaneous population death may be a biological oddity
      restricted to rat CHL cells, we suggest that this death programme is responsible
      for the eradication of cancer cells following treatment with an inhibitor
      administered exogenously.

PMID- 29226463
TI  - Which limb is it? Responses to vibrotactile stimulation in early infancy.
AB  - This study focuses on how the body schema develops during the first months of
      life, by investigating infants' motor responses to localized vibrotactile
      stimulation on their limbs. Vibrotactile stimulation was provided by small
      buzzers that were attached to the infants' four limbs one at a time. Four age
      groups were compared cross-sectionally (3-, 4-, 5-, and 6-month-olds). We show
      that before they actually reach for the buzzer, which, according to previous
      studies, occurs around 7-8 months of age, infants demonstrate emerging knowledge
      about their body's configuration by producing specific movement patterns
      associated with the stimulated body area. At 3 months, infants responded with an
      increase in general activity when the buzzer was placed on the body,
      independently of the vibrator's location. Differentiated topographical awareness
      of the body seemed to appear around 5 months, with specific responses resulting
      from stimulation of the hands emerging first, followed by the differentiation of
      movement patterns associated with the stimulation of the feet. Qualitative
      analyses revealed specific movement types reliably associated with each
      stimulated location by 6 months of age, possibly preparing infants' ability to
      actually reach for the vibrating target. We discuss this result in relation to
      newborns' ability to learn specific movement patterns through intersensory
      contingency. Statement of contribution what is already known on infants'
      sensorimotor knowledge about their own bodies 3-month-olds readily learn to
      produce specific limb movements to obtain a desired effect (movement of a
      mobile). infants detect temporal and spatial correspondences between events
      involving their own body and visual events. what the present study adds until 4-5
      months of age, infants mostly produce general motor responses to localized touch.
      this is because in the present study, infants could not rely on immediate
      contingent feedback. we propose a cephalocaudal developmental trend of
      topographic differentiation of body areas.

PMID- 29226464
TI  - Place of death in the Snowy Monaro region of New South Wales: A study of
      residents who died of a condition amenable to palliative care.
AB  - OBJECTIVE: To describe the place of death of residents in a rural region of New
      South Wales. DESIGN: Cross-sectional quantitative study using death data
      collected from local funeral directors (in person and websites), residential aged
      care facilities, one multipurpose heath service and obituary notices in the local
      media (newspapers/radio). SETTING: Snowy Monaro region (New South Wales
      Australia). PARTICIPANTS: Residents, with advanced frailty or one of 10
      conditions amenable to palliative care, who died between 1 February 2015 and 31
      May 2016. MAIN OUTCOME MEASURE: Place of death. RESULTS: Of 224 deaths in this
      period, 138 were considered amenable to palliative care. Twelve per cent of these
      deaths occurred in a private residence, 38% in the usual place of residence and
      91% within the region. CONCLUSION: Most rural residents with conditions amenable
      to palliative care died in the region. Most did not die in their usual place of
      residence. Further qualitative work is needed to determine palliative care
      patients' and family caregivers' preferences for, and the importance placed on,
      place of death. While there may be a need to support an increase in home deaths,
      local rural hospitals and residential aged-care facilities must not be overlooked
      as a substitute for inpatient hospices.

PMID- 29226465
TI  - Supplemental oxygen therapy does not affect the systemic inflammatory response to
      acute myocardial infarction.
AB  - BACKGROUND: Oxygen therapy has been used routinely in normoxemic patients with
      suspected acute myocardial infarction (AMI) despite limited evidence supporting a
      beneficial effect. AMI is associated with a systemic inflammation. Here, we
      hypothesized that the inflammatory response to AMI is potentiated by oxygen
      therapy. METHODS: The DETermination of the role of Oxygen in suspected Acute
      Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with
      suspected AMI to receive oxygen at 6 L min-1 for 6-12 h or ambient air. For this
      prespecified subgroup analysis, we recruited patients with confirmed AMI from two
      sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later.
      Ninety-two inflammatory biomarkers were analysed using proximity extension assay
      technology, to evaluate the effect of oxygen on the systemic inflammatory
      response to AMI. RESULTS: Plasma from 144 AMI patients was analysed whereof 76
      (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a
      significant increase, whereas 13 were decreased 5-7 h after randomization. The
      inflammatory response did not differ between the two treatment groups neither did
      plasma troponin T levels. After adjustment for increase in troponin T over time,
      age and sex, the release of inflammation-related biomarkers was still similar in
      the groups. CONCLUSIONS: In a randomized controlled setting of normoxemic
      patients with AMI, the use of supplemental oxygen did not have any significant
      impact on the early release of systemic inflammatory markers.

PMID- 29226466
TI  - Childhood-Onset Cluster Headache: Observations From a Personal Case-Series and
      Review of the Literature.
AB  - BACKGROUND/OBJECTIVES: Puberty seems to be a turning point in cluster headache
      (CH) onset. To verify its influence on CH phenotype, we focused on cases with
      onset <=13 years. A review of the literature follows. METHOD: We considered CH
      cases with age-of-onset <=13 years evaluated at our center between 1975 and 2015;
      these cases were matched by sex to two consecutive patients with age-of-onset as
      close as possible (+/-2 years) to the median age-of-onset of the overall CH
      population. RESULTS: Of the overall 808 cases (585 men and 223 women, M:F ratio =
      2.6), 38 patients (20 men and 18 women, M:F ratio = 1.1) had pediatric onset
      (PO). The diagnostic delay was significantly higher among cases with PO (21.2 +/-
      12.4 years, P < .0001). In this group, females had more frequently a chronic
      course and a familiarity for CH. Men with PO had some significant distinctive
      features, including higher frequency and longer duration of headache attacks, and
      higher proportion of various cranial autonomic and migraine-like symptoms.
      CONCLUSIONS: We confirmed that CH with childhood onset does not show a male
      predominance, which was actually inverted for chronic cases. Furthermore, males
      with PO seem to have a specific clinical phenotype.

PMID- 29226468
TI  - Peptide Integrated Optics.
AB  - Bio-nanophotonics is a wide field in which advanced optical materials,
      biomedicine, fundamental optics, and nanotechnology are combined and result in
      the development of biomedical optical chips. Silk fibers or synthetic
      bioabsorbable polymers are the main light-guiding components. In this work, an
      advanced concept of integrated bio-optics is proposed, which is based on
      bioinspired peptide optical materials exhibiting wide optical transparency,
      nonlinear and electrooptical properties, and effective passive and active
      waveguiding. Developed new technology combining bottom-up controlled deposition
      of peptide planar wafers of a large area and top-down focus ion beam lithography
      provides direct fabrication of peptide optical integrated circuits. Finding a
      deep modification of peptide optical properties by reconformation of biological
      secondary structure from native phase to beta-sheet architecture is followed by
      the appearance of visible fluorescence and unexpected transition from a native
      passive optical waveguiding to an active one. Original biocompatibility,
      switchable regimes of waveguiding, and multifunctional nonlinear optical
      properties make these new peptide planar optical materials attractive for
      application in emerging technology of lab-on-biochips, combining biomedical
      photonic and electronic circuits toward medical diagnosis, light-activated
      therapy, and health monitoring.

PMID- 29226467
TI  - Axon guidance pathways and the control of gene expression.
AB  - Axons need to be properly guided to their targets to form synaptic connections,
      and this requires interactions between highly conserved extracellular and
      transmembrane ligands and their cell surface receptors. The majority of studies
      on axon guidance signaling pathways have focused on the role of these pathways in
      rearranging the local cytoskeleton and plasma membrane in growth cones and axons.
      However, a smaller body of work has demonstrated that axon guidance signaling
      pathways also control gene expression via local translation and transcription.
      Recent studies on axon guidance ligands and receptors have begun to uncover the
      requirements for these alternative mechanisms in processes required for neural
      circuit formation: axon guidance, synaptogenesis, and cell migration.
      Understanding the mechanisms by which axon guidance signaling regulates local
      translation and transcription will create a more complete picture of neural
      circuit formation, and they may be applied more broadly to other tissues where
      axon guidance ligands and receptors are required for morphogenesis. Developmental
      Dynamics 247:571-580, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226469
TI  - Surgical anatomy of the superficial temporal artery to prevent facial nerve
      injury during arterial biopsy.
AB  - To investigate the topographical relationship between the frontal branch of the
      superficial temporal artery (FSTA) and the temporal branch of the facial nerve
      (TFN) with the aim of preventing nerve injury during FSTA biopsy. Fifty-seven
      hemifaces of 33 cadavers were dissected. Vertical lines drawn to the lateral
      orbital margin (LOM) and the superior root of the helix were used as the anterior
      and posterior reference positions, respectively. Horizontal lines drawn through
      the supraorbital margin and lateral canthus were used as the superior and
      inferior reference points, respectively. The depth and course relationships of
      the FSTA and TFN were examined. Midpoints between the FSTA and TFN are situated
      approximately 6.0 and 4.5 cm posterior to the lateral orbital margin at the
      levels of the lateral canthus and supraorbital margin, respectively. The TFN is
      generally situated 1-2 cm anteriorly and inferiorly to the FSTA in the temporal
      region. However, in two cases (3.6%), the TFN ran just underneath the FSTA with
      only a very small safe distance, making it highly vulnerable to iatrogenic
      injury. In conclusion, when performing an FSTA biopsy, the surgeon should not
      dissect below the superficial temporal fascia because there is an overlap between
      the course of the FSTA and the TFN in a minority of cases. Also, surgical
      incisions should be made outside the area delineated by an oblique line passing
      through the points 6.0 and 4.5 cm posterior to the lateral orbital margin at the
      levels of the lateral canthus and the supraorbital margin, respectively. Clin.
      Anat. 31:608-613, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226470
TI  - Photo-Crosslinkable Unnatural Amino Acids Enable Facile Synthesis of
      Thermoresponsive Nano- to Microgels of Intrinsically Disordered Polypeptides.
AB  - Hydrogel particles are versatile materials that provide exquisite, tunable
      control over the sequestration and delivery of materials in pharmaceutics, tissue
      engineering, and photonics. The favorable properties of hydrogel particles depend
      largely on their size, and particles ranging from nanometers to micrometers are
      used in different applications. Previous studies have only successfully
      fabricated these particles in one specific size regime and required a variety of
      materials and fabrication methods. A simple yet powerful system is developed to
      easily tune the size of polypeptide-based, thermoresponsive hydrogel particles,
      from the nano- to microscale, using a single starting material. Particle size is
      controlled by the self-assembly and unique phase transition behavior of elastin
      like polypeptides in bulk and within microfluidic-generated droplets. These
      particles are then stabilized through ultraviolet irradiation of a photo
      crosslinkable unnatural amino acid (UAA) cotranslationally incorporated into the
      parent polypeptide. The thermoresponsive property of these particles provides an
      active mechanism for actuation and a dynamic responsive to the environment. This
      work represents a fundamental advance in the generation of crosslinked
      biomaterials, especially in the form of soft matter colloids, and is one of the
      first demonstrations of successful use of UAAs in generating a novel material.

PMID- 29226471
TI  - A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating
      Properties of Cenderitide in Subjects With Stable Chronic Heart Failure.
AB  - Cenderitide is a novel designer natriuretic peptide (NP) composed of C-type
      natriuretic peptide (CNP) fused to the C-terminus of Dendroaspis natriuretic
      peptide (DNP). Cenderitide was engineered to coactivate the two NP receptors,
      particulate guanylyl cyclase (pGC)-A and -B. The rationale for its design was to
      achieve the renal-enhancing and antifibrotic properties of dual receptor
      activation, but without clinically significant hypotension. Here we report the
      first clinical trial on the safety, tolerability, and cyclic guanosine
      monophosphate (cGMP) activating properties of Cenderitide in subjects with stable
      heart failure (HF). Four-hour infusion of Cenderitide was safe, well-tolerated,
      and significantly increased plasma cGMP levels and urinary cGMP excretion without
      adverse effects with no change in blood pressure. Thus, Cenderitide has a
      favorable safety profile and expected pharmacological effects in stable human HF.
      Our results support further investigations of Cenderitide in HF as a potential
      future cGMP-enhancing therapeutic strategy.

PMID- 29226472
TI  - Cost-utility analysis of idelalisib in combination with rituximab in relapsed or
      refractory chronic lymphocytic leukaemia.
AB  - OBJECTIVE: To evaluate the incremental cost-utility ratio (ICUR) of idelalisib in
      combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment
      of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia
      (CLL), from the Spanish National Health System (NHS) perspective. METHODS: A
      partitioned survival Markov model for a lifetime horizon (30 years) was developed
      to estimate costs (?, 2016) and quality-adjusted life years (QALY) with IR and R.
      Initial cohort included patients with CLL receiving a second or subsequent line
      (2L) of treatment with IR or R. Survival data were based on CLL clinical trial.
      Drug, administration, monitoring, adverse events and clinical management of CLL
      costs were included in the model. Costs and outcomes were discounted using a 3%
      annually. Deterministic and probabilistic sensitivity analyses (PSA) were
      performed. RESULTS: Compared to R, 2L IR treatment resulted in QALY gain of 3.147
      (4.965 versus 1.818). Total costs were ?118 254 for IR versus ?23 874 for R. ICUR
      was ?29 990/QALY gained with IR versus R. In the PSA, IR was cost-effective in
      78% of iterations using a threshold of ?45 000/QALY. CONCLUSION: IR can be
      considered a cost-effective treatment compared to R, in the treatment of R/R CLL
      patients for the Spanish NHS.

PMID- 29226474
TI  - Cerebroplacental ratio and fetal response to maternal extracorporeal soluble fms
      like tyrosine kinase-1 removal.

PMID- 29226473
TI  - Contributions to nucleosome dynamics in chromatin from interactive propagation of
      phosphorylation/acetylation and inducible histone lysine basicities.
AB  - The effect of phosphorylation on the basicities of amines in histone H3 peptides
      and their acetylation kinetics is probed with a mild chemical acetylating agent.
      Phosphorylation of Ser-10 lowers the rate of chemical acetylation of Lys-9, Lys
      14, and Lys-18 by methyl acetyl phosphate in that order consistent with a higher
      pKa of these Lys residues induced by phosphorylation; basicities increase up to 3
      pKa units as a function of distance from Ser-10 phosphate. Enzymic acetylation of
      Lys residues with high pKa values in nucleosomes is also expected to be enhanced
      by phosphorylation, consistent with the known mechanism involving binding of
      protonated amines to N-acetyltransferases; fetal hemoglobin has a related linkage
      of increased basicity at a specific site, its acetylation, and a resulting
      decrease in subunit interaction strength. In the absence of a phosphate on Ser
      10, the amines of Lys-9, Lys-14, and Lys-18 have lowered pKa values. Chemical
      acetylation of glycine and glycinamide have analogous kinetic profiles to the
      histone peptides but the phosphate inductive effect in histone H3 is more potent
      since the linkage between phosphorylation and acetylation is propagated with a
      range extending 9-10 amino acids in either direction from the phosphorylation
      site enhancing protonation of amino groups. We conclude that lysine amine
      basicities in histone tails are not static but inducible and variable due to a
      dynamic and immediate interaction between phosphorylation/acetylation that may
      contribute to inactive heterochromatin by compaction through such Ser phosphate
      Lys amine electrostatic interactions and their relaxation by acetylation in
      euchromatin.

PMID- 29226475
TI  - Double-scope method for creating a straight submucosal tunnel during peroral
      endoscopic myotomy.

PMID- 29226477
TI  - Concise Review: Cell Therapy for Critical Limb Ischemia: An Integrated Review of
      Preclinical and Clinical Studies.
AB  - Critical limb ischemia (CLI), the most severe form of peripheral artery disease,
      is characterized by pain at rest and non-healing ulcers in the lower extremities.
      For patients with CLI, where the extent of atherosclerotic artery occlusion is
      too severe for surgical bypass or percutaneous interventions, limb amputation
      remains the only treatment option. Thus, cell-based therapy to restore perfusion
      and promote wound healing in patients with CLI is under intense investigation.
      Despite promising preclinical studies in animal models, transplantation of bone
      marrow (BM)-derived cell populations in patients with CLI has shown limited
      benefit preventing limb amputation. Early trials injected heterogenous
      mononuclear cells containing a low frequency of cells with pro-vascular
      regenerative functions. Most trials transferred autologous cells damaged by
      chronic disease that demonstrated poor survival in the ischemic environment and
      impaired function conferred by atherosclerotic or diabetic co-morbidities.
      Finally, recent preclinical studies suggest optimized blood vessel formation may
      require paracrine and/or structural contributions from multiple progenitor cell
      lineages, angiocrine-secretory myeloid cells derived from hematopoietic
      progenitor cells, tubule-forming endothelial cells generated by circulating or
      vessel-resident endothelial precursors, and vessel-stabilizing perivascular cells
      derived from mesenchymal stem cells. Understanding how stem cells co-ordinate the
      myriad of cells and signals required for stable revascularization remains the key
      to translating the potential of stem cells into curative therapies for CLI. Thus,
      combination delivery of multiple cell types within supportive bioengineered
      matricies may represent a new direction to improve cell therapy strategies for
      CLI. Stem Cells 2018;36:161-171.

PMID- 29226476
TI  - Differences in the Activity of Endogenous Bone Morphogenetic Protein Signaling
      Impact on the Ability of Induced Pluripotent Stem Cells to Differentiate to
      Corneal Epithelial-Like Cells.
AB  - Cornea is a clear outermost layer of the eye which enables transmission of light
      onto the retina. The transparent corneal epithelium is regenerated by limbal stem
      cells (LSCs), whose loss/dysfunction results in LSCs deficiency (LSCD). Ex vivo
      expansion of autologous LSCs obtained from patient's healthy eye followed by
      transplantation onto the LSCs damaged/deficient eye, has provided a successful
      treatment for unilateral LSCD. However, this is not applicable to patient with
      total bilateral LSCD, where LSCs are lost/damaged from both eyes. We investigated
      the potential of human induced pluripotent stem cell (hiPSC) to differentiate
      into corneal epithelial-like cells as a source of autologous stem cell treatment
      for patients with total bilateral LSCD. Our study showed that combined addition
      of bone morphogenetic protein 4 (BMP4), all trans-retinoic acid and epidermal
      growth factor for the first 9 days of differentiation followed by cell-replating
      on collagen-IV-coated surfaces with a corneal-specific-epithelial cell media for
      an additional 11 days, resulted in step wise differentiation of human embryonic
      stem cells (hESC) to corneal epithelial progenitors and mature corneal epithelial
      like cells. We observed differences in the ability of hiPSC lines to undergo
      differentiation to corneal epithelial-like cells which were dependent on the
      level of endogenous BMP signaling and could be restored via the activation of
      this signaling pathway by a specific transforming growth factor beta inhibitor
      (SB431542). Together our data reveal a differential ability of hiPSC lines to
      generate corneal epithelial cells which is underlined by the activity of
      endogenous BMP signaling pathway. Stem Cells 2018;36:337-348.

PMID- 29226478
TI  - Improved protein splicing using embedded split inteins.
AB  - Naturally split inteins mediate a traceless protein ligation process known as
      protein trans-splicing (PTS). Although frequently used in protein engineering
      applications, the efficiency of PTS can be reduced by the tendency of some split
      intein fusion constructs to aggregate; a consequence of the fragmented nature of
      the split intein itself or the polypeptide to which it is fused (the extein).
      Here, we report a strategy to help address this liability. This involves
      embedding the split intein within a protein sequence designed to stabilize either
      the intein fragment itself or the appended extein. We expect this approach to
      increase the scope of PTS-based protein engineering efforts.

PMID- 29226479
TI  - Metabolite profiling and isolation of biologically active compounds from Scadoxus
      puniceus, a highly traded South African medicinal plant.
AB  - Scadoxus puniceus (Amaryllidaceae), a medicinal plant of high value in South
      Africa, is used as a component of a traditional herbal tonic prescribed to treat
      several ailments. Ultra-high performance liquid chromatography-tandem mass
      spectrometry quantified the phenolic compounds in different organs of S.
      puniceus. Gravity column chromatography was used to separate fractions and active
      compounds. The structure of these compounds was determined using 1D and 2D
      nuclear magnetic resonance and mass spectroscopic techniques. A microplate
      technique was used to determine the acetylcholinesterase inhibitory activity of
      the pure compounds. Metabolite profiling revealed a greater profusion of
      hydroxycinnamic acids (69.5%), as opposed to hydroxybenzoic acids (30.5%).
      Chlorogenic acid was the most abundant (49.6% of hydroxycinnamic acids) compound.
      In addition to chlorogenic acid, the study is the first to report the presence of
      sinapic, gallic, and m-hydroxybenzoic acids in the Amaryllidaceae.
      Chromatographic separation of S. puniceus led to the isolation of haemanthamine
      (1), haemanthidine (2), and a rare chlorinated amide, metolachlor (3), the
      natural occurrence of which is described for the first time. Haemanthamine,
      haemanthidine, and metolachlor displayed strong acetylcholinesterase inhibitory
      activity (IC50 ; 23.1, 23.7, and 11.5 MUM, respectively). These results
      substantiate the frequent use of S. puniceus as a medicinal plant and hold much
      promise for further pharmaceutical development.

PMID- 29226480
TI  - Successful pancreas transplantation alone is associated with excellent self
      identified health score and glucose control: A retrospective study from a high
      volume center in the United States.
AB  - BACKGROUND: The benefits of pancreas transplantation are often difficult to
      measure. Here, we sought to determine the difference in quality of life for
      diabetic patients with and without a functional pancreas transplant alone (PTA).
      METHODS: Pancreas transplant alone cases from 1993 to 2015 were considered. An
      IRB-approved survey inclusive of 15 questions spanning four domains was employed.
      Chi-square, Fisher's exact, and the T test were used where appropriate. RESULTS:
      A total of 137 PTAs were performed during the study period. Of those reached (n =
      32), 94% responded to the survey. Self-reported health scores were better (2.1 vs
      3.0) for those with functioning pancreata (n = 18) vs those with a non-functional
      pancreas (n = 14), respectively (P = .036). Those with a functional pancreas had
      a HgbA1c of 5.3, vs 7.7 for a non-functional pancreas (P = .016). Significant
      hypoglycemia was reported in two of 18 with a functional transplant vs nine of 14
      patients with a failed transplant (P = .003). Daily frustration with blood sugar
      affecting quality of life was significantly higher for patients with non
      functional pancreas grafts (P < .001). CONCLUSIONS: Pancreas transplantation
      alone is associated with better glucose control than insulin. In addition,
      recipients of functional PTAs have improved quality of life and better overall
      health scores than those with failed grafts.

PMID- 29226481
TI  - No major differences in outcomes between the initial and relapse episodes in
      patients with thrombotic thrombocytopenic purpura: The experience from the Ohio
      State University Registry.

PMID- 29226482
TI  - Using facial muscular movements to understand young children's emotion regulation
      and concurrent neural activation.
AB  - Individual differences in young children's frustration responses set the stage
      for myriad developmental outcomes and represent an area of intense empirical
      interest. Emotion regulation is hypothesized to comprise the interplay of complex
      behaviors, such as facial expressions, and activation of concurrent underlying
      neural systems. At present, however, the literature has mostly examined
      children's observed emotion regulation behaviors and assumed underlying brain
      activation through separate investigations, resulting in theoretical gaps in our
      understanding of how children regulate emotion in vivo. Our goal was to elucidate
      links between young children's emotion regulation-related neural activation,
      facial muscular movements, and parent-rated temperamental emotion regulation.
      Sixty-five children (age 3-7) completed a frustration-inducing computer task
      while lateral prefrontal cortex (LPFC) activation and concurrent facial
      expressions were recorded. Negative facial expressions with eye constriction were
      inversely associated with both parent-rated temperamental emotion regulation and
      concurrent LPFC activation. Moreover, we found evidence that positive expressions
      with eye constriction during frustration may be associated with stronger LPFC
      activation. Results suggest a correspondence between facial expressions and LPFC
      activation that may explicate how children regulate emotion in real time.

PMID- 29226483
TI  - Boron Nanowheels with Axles Containing Noble Gas Atoms: Viable Noble Gas Bound
      M(c)B10- Clusters (M=Nb, Ta).
AB  - The viability of noble gas axled boron nanowheels Ngn M(c)B10- (Ng=Ar-Rn; M=Nb,
      Ta; n=1, 2) is explored by ab initio computations. In the resulting Ng2 -M
      complexes, the Ng-M-Ng nanorod passes through the center of the B10- ring,
      providing them with an inverse sandwich-like structure. While in the singly Ng
      bound analogue, the Ng binding enthalpy Hb at 298 K ranges from 2.5 to 10.6 kcal
      mol-1 , in doubly Ng bound cases it becomes very low for the Ng2 M(c)B10- 
      >Ng+NgM(c)B10- dissociation channel, except for the case of Rn, for which the
      corresponding Hb values are 3.4 (Nb) and 4.0 kcal mol-1 (Ta). For a given Ng, Ta
      has slightly higher Ng-binding ability than Nb. The corresponding free-energy
      changes indicate that these systems, particularly the Xe and Rn complexes, are
      good candidates for experimental realization in a low-temperature matrix. The Ng
      M bonds were found to be covalent in nature, as reflected in their large Wiberg
      bond indices, formation of a 2c-2e sigma orbital between Ng and M centers in
      natural bond orbital and adaptive natural density partitioning (AdNDP) analyses,
      and the short Ng-M distances. Energy decomposition analysis and a study on the
      natural orbitals for chemical valence show that the Ng-M contact is supported
      mainly by the orbital and electrostatic interactions, with almost equal
      contributions. Although both the Ng->M sigma donation and Ng<-M pi backdonation
      play roles in the origin of orbital interaction, the former is significantly
      dominant over the latter. Further, AdNDP analysis indicates that the doubly
      aromatic character (both sigma and pi) in MB10- clusters is not perturbed by the
      interaction with Ng atoms.

PMID- 29226484
TI  - Family conflict is associated with longitudinal changes in insular-striatal
      functional connectivity during adolescent risk taking under maternal influence.
AB  - Maternal presence has marked effects on adolescent neurocognition during risk
      taking, influencing teenagers to make safer decisions. However, it is currently
      unknown whether maternal buffering changes over the course of adolescence itself,
      and whether its effects are robust to individual differences in family
      relationship quality. In the current longitudinal study, 23 adolescents completed
      a risk-taking task under maternal presence during an fMRI scan before and after
      the transition to high school. Behavioral results reveal that adolescent risk
      taking increased under maternal presence across a one-year period. At the neural
      level, we found that adolescents reporting higher family conflict showed
      longitudinal increases in functional coupling between the anterior insula (AI)
      and ventral striatum (VS) when making safe decisions in the presence of their
      mother, which was associated with increased real-world risk taking. These
      findings show that individual differences in family relationship quality
      undermine effective development of AI-VS connectivity resulting in increased risk
      taking.

PMID- 29226485
TI  - Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation
      in a rat model.
AB  - OBJECTIVE: After recurrent laryngeal nerve injury (RLN), spontaneous
      reinnervation of the larynx occurs with input from multiple sources. The purpose
      of this study was to determine the timing and efficiency of reinnervation across
      a resected RLN segment in a rat model of RLN injury. STUDY DESIGN: Animal study.
      METHODS: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm
      segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after
      nerve injury to harvest the larynx and trachea for immunohistologic analysis. The
      distal RLN segment was stained with neurofilament, and axons were counted and
      compared to the nonoperated side. Thyroarytenoid (TA) muscles were stained with
      alpha-bungarotoxin, synaptophysin, and neurofilament to identify intact
      neuromuscular junctions (NMJ). The number of intact NMJs from the denervated side
      was compared to the nonoperated side. RESULTS: Nerve fibers regenerated across
      the resected RLN gap into the distal recurrent laryngeal nerve to innervate the
      TA muscle. The number of nerve fibers in the distal nerve segment increased over
      time and reached the normal number by 12 weeks postdenervation. Axons formed
      intact neuromuscular junctions in the TA, with 48.8% +/- 16.7% of the normal
      number of intact NMJs at 4 weeks and 88.3% +/- 30.1% of the normal number by 12
      weeks. CONCLUSION: Following resection of an RLN segment in a rat model, nerve
      fibers spontaneously regenerate through the distal segment of the transected
      nerve and form intact NMJs in order to reinnervate the TA muscle. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 128:E117-E122, 2018.

PMID- 29226486
TI  - Associations between and development of cool and hot executive functions across
      early childhood.
AB  - This study explored the development of cool and hot EF skills across early
      childhood. Children 4.5- to 5.5-years-old (N = 80) completed performance-based
      assessments of cool EF (inhibition and working memory), hot EF (affective
      decision-making and delay of gratification) at three time points across 12
      months. Cool EF task performance was consistently correlated with early
      childhood, but hot EF task performance was not. Performance on cool EF tasks
      showed significant improvements over early childhood, but performance on hot EF
      tasks did not. During early childhood performance on delay of gratification and
      affective decision-making tasks may therefore be unrelated and show limited
      sensitivity to improvement. Statement of contribution What is already known about
      cool and hot EF An EF model has been proposed that distinguishes between cool
      cognitive and hot-affective skills. Findings regarding whether cool and hot EF
      are distinct in early childhood are mixed. Hot EF skills, compared to cool EF
      abilities, are thought to develop more gradually. What the present study adds to
      understanding of cool and hot EF Performance on cool EF tasks and hot delay of
      gratification were associated in early childhood. Performance on hot EF tasks was
      not related, meaning they do not tap the same underlying factor. Age related
      gains in hot EF were not found, but 5-year-olds had better hot EF than 4-year
      olds.

PMID- 29226487
TI  - Prenatal diagnostic testing and atypical chromosome abnormalities following
      combined first-trimester screening: implications for contingent models of non
      invasive prenatal testing.
AB  - OBJECTIVES: To investigate by means of a population-based analysis of a cohort of
      women who underwent combined first-trimester screening (CFTS), changes in uptake
      of invasive prenatal diagnosis according to risk of trisomy 21 (T21) on CFTS, and
      prevalence and methods for ascertainment of atypical chromosome abnormalities.
      METHODS: This was a retrospective cohort study using state-wide prenatal datasets
      from Victoria, Australia. A three-step approach was taken to analyze the data:
      (1) linkage of records between serum screening and diagnostic results; (2)
      comparison of rates of diagnostic testing according to CFTS T21 risk result
      category in a 2014-2015 cohort with those of a historical 2002-2004 cohort; (3)
      detailed analysis of atypical abnormalities in the 2014-2015 group according to
      CFTS T21 risk result, individual serum analyte level and other indications for
      invasive diagnostic testing. RESULTS: In 2014-2015, there were 100 418 CFTS
      results issued for 146 776 births (68.4%). The overall prevalence of atypical
      chromosome abnormalities in the entire CFTS cohort was 0.10% and was highest in
      those with CFTS T21 risk > 1 in 10 (4.6%), or serum analyte levels < 0.2
      multiples of the median (MoM) (6.9% for pregnancy-associated plasma protein-A
      (PAPP-A) and 5.2% for beta-human chorionic gonadotropin (beta-hCG)). Almost half
      (49.2%) of women with PAPP-A < 0.2 MoM had a risk for T21 on CFTS of less than 1
      in 100. The majority (55%) of atypical abnormalities occurred in women with CFTS
      T21 risk below 1 in 300, and were most commonly detected on ultrasound
      examination (47.1%). CONCLUSION: Concerns regarding missed diagnoses of atypical
      chromosome abnormalities when non-invasive prenatal testing is offered after a
      result of high risk on CFTS can be mitigated if invasive diagnostic testing is
      offered to those women with CFTS T21 risk of > 1 in 100, serum PAPP-A or beta-hCG
      < 0.2 MoM, or ultrasound-detected abnormality. This has implications for
      contingent models of screening. Copyright (c) 2017 ISUOG. Published by John Wiley
      & Sons Ltd.

PMID- 29226488
TI  - Rechargeable Aqueous Zinc-Ion Battery Based on Porous Framework Zinc Pyrovanadate
      Intercalation Cathode.
AB  - In this work, a microwave approach is developed to rapidly synthesize ultralong
      zinc pyrovanadate (Zn3 V2 O7 (OH)2 .2H2 O, ZVO) nanowires with a porous crystal
      framework. It is shown that our synthesis strategy can easily be extended to
      fabricate other metal pyrovanadate compounds. The zinc pyrovanadate nanowires
      show significantly improved electrochemical performance when used as
      intercalation cathode for aqueous zinc-ion battery. Specifically, the ZVO cathode
      delivers high capacities of 213 and 76 mA h g-1 at current densities of 50 and
      3000 mA g-1 , respectively. Furthermore, the Zn//ZVO cells show good cycling
      stability up to 300 cycles. The estimated energy density of this Zn cell is
      ~214Wh kg-1 , which is much higher than commercial lead-acid batteries.
      Significant insight into the Zn-storage mechanism in the pyrovanadate cathodes is
      presented using multiple analytical methods. In addition, it is shown that our
      prototype device can power a 1.5 V temperature sensor for at least 24 h.

PMID- 29226489
TI  - Inhibitory effect of sulphated polysaccharide porphyran (isolated from Porphyra
      yezoensis) on RANKL-induced differentiation of RAW264.7 cells into osteoclasts.
AB  - Safe and efficient therapeutic agents for bone diseases are required in natural
      sources. We previously found that edible seaweed-derived polysaccharide porphyran
      exhibited anti-inflammatory effects through the down regulation of nuclear factor
      kappaB. The aim of this study was to investigate the availability of porphyran as
      a therapeutic agent for bone diseases. The effects of porphyran on receptor
      activator of nuclear factor kappaB ligand (RANKL)-induced osteoclastogenesis in
      RAW264.7 cells were examined. Porphyran suppressed RANKL-induced osteoclast
      formation in a concentration-dependent manner (6.25-50 MUg/ml) without any
      cytotoxic effects. Furthermore, real-time polymerase chain reaction analyses
      indicated that porphyran at 50 MUg/ml significantly attenuated the RANKL-induced
      increase in the mRNA levels of osteoclastogenesis-related marker genes such as
      nuclear factor of activated T cells, tartrate-resistant acid phosphatase,
      cathepsin K, and matrix metalloproteinase-9 in RAW264.7 cells. To our knowledge,
      this is the first report showing that edible-seaweed-derived polysaccharide
      porphyran can suppress RANKL-induced osteoclastogenesis. Our results suggest that
      porphyran can be used as a safe therapeutic agent to improve osteoclast-related
      pathological conditions.

PMID- 29226490
TI  - A Water-Processable and Bioactive Multivalent Graphene Nanoink for Highly
      Flexible Bioelectronic Films and Nanofibers.
AB  - The capabilities of conductive nanomaterials to be produced in liquid form with
      well-defined chemical, physical, and biological properties are highly important
      for the construction of next-generation flexible bioelectronic devices. Although
      functional graphene nanomaterials can serve as attractive liquid nanoink
      platforms for the fabrication of bioelectronics, scalable synthesis of graphene
      nanoink with an integration of high colloidal stability, water processability,
      electrochemical activity, and especially bioactivity remains a major challenge.
      Here, a facile and scalable synthesis of supramolecular-functionalized
      multivalent graphene nanoink (mGN-ink) via [2+1] nitrene cycloaddition is
      reported. The mGN-ink unambiguously displays a well-defined and flat 2D
      morphology and shows good water processability and bioactivity. The uniquely
      chemical, physical, and biological properties of mGN-ink endow the constructed
      bioelectronic films and nanofibers with high flexibility and durability, suitable
      conductivity and electrochemical activity, and most importantly, good cellular
      compatibility and a highly efficient control of stem-cell spreading and
      orientation. Overall, for the first time, a water-processable and bioactive mGN
      ink is developed for the design of flexible and electrochemically active
      bioelectronic composites and devices, which not only presents manifold
      possibilities for electronic-cellular applications but also establishes a new
      pathway for adapting macroscopic usages of graphene nanomaterials in bionic,
      biomedical, electronic, and even energy fields.

PMID- 29226492
TI  - Molecular mechanisms underlying monosynaptic sensory-motor circuit development in
      the spinal cord.
AB  - Motor behaviors are precisely controlled by the integration of sensory and motor
      systems in the central nervous system (CNS). Proprioceptive sensory neurons, key
      components of the sensory system, are located in the dorsal root ganglia and
      project axons both centrally to the spinal cord and peripherally to muscles and
      tendons, communicating peripheral information about the body to the CNS. Changes
      in muscle length detected by muscle spindles, and tension variations in tendons
      conveyed by Golgi tendon organs, are communicated to the CNS through group Ia
      /II, and Ib proprioceptive sensory afferents, respectively. Group Ib
      proprioceptive sensory neurons connect with motor neurons indirectly through
      spinal interneurons, whereas group Ia/II axons form both direct (monosynaptic)
      and indirect connections with motor neurons. Although monosynaptic sensory-motor
      circuits between spindle proprioceptive sensory neurons and motor neurons have
      been extensively studied since 1950s, the molecular mechanisms underlying their
      formation and upkeep have only recently begun to be understood. We will discuss
      our current understanding of the molecular foundation of monosynaptic circuit
      development and maintenance involving proprioceptive sensory neurons and motor
      neurons in the mammalian spinal cord. Developmental Dynamics 247:581-587, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29226494
TI  - How does routinely delivered cognitive-behavioural therapy for gambling disorder
      compare to "gold standard" clinical trial?
AB  - Currently, it is unknown whether treatment outcomes derived from randomized
      controlled trials (RCTs) of cognitive-behavioural therapy (CBT) for problem
      gamblers still hold when applied to patients seen in routine practice. Thus, data
      from an RCT of cognitive therapy versus exposure therapy for problem gambling
      versus patients of a gambling help service were compared. Assessments of problem
      gambling severity, psychosocial impairment, and alcohol use were undertaken at
      baseline and post-treatment and evaluated within a counterfactual framework.
      Findings showed that the contrast between routine CBT for pokies and horse
      betting had a significant effect, indicative of a 62% lower gambling urge score
      if routine CBT recipients had all been horse/track betters opposed to gambling
      with "pokies." However, the majority of contrasts indicated therapeutic outcomes
      achieved in routine CBT treatments were of equivalent robustness relative to RCT
      conditions. The present findings infer routine practice treatment outcomes are as
      efficacious as those generated in RCT contexts.

PMID- 29226493
TI  - A prospective study comparing perioperative anxiety and posthospital behavior in
      children with autism spectrum disorder vs typically developing children
      undergoing outpatient surgery.
AB  - BACKGROUND: Research describing the experience of youth with autism spectrum
      disorders in the perioperative setting is limited. This study compared youth with
      autism spectrum disorder to typically developing children in the perioperative
      setting and examined group differences in: child anxiety, parent anxiety,
      premedication patterns, induction compliance, and changes in behavior
      postprocedure. METHODS: Participants were 60 youth (32 with autism spectrum
      disorder, 28 typically developing) of ages 2-19 years undergoing outpatient
      surgery and their parents. Parents and research assistants rated children's
      anxiety at 3 time points (waiting room, preoperative holding, separation), and
      parents rated their own anxiety in the waiting room and at separation. The
      anesthesiologist rated induction compliance. Postprocedure behavior change was
      assessed via phone survey 1 and 7 days postprocedure. Analyses examined group
      differences in anxiety, medication patterns, and behavior. RESULTS: Children with
      autism spectrum disorder had higher research assistant reported anxiety than
      typically developing youth in the holding room only. There were no group
      differences in parent report of their own anxiety or their child's anxiety across
      time points. Compared to typically developing youth, children with autism
      spectrum disorder were more likely to receive a premedication (including
      nonstandard premedication), and had poorer induction compliance. Groups did not
      differ on posthospital behavior change 1 or 7 days postsurgery. CONCLUSION:
      Findings revealed ratings of anxiety in youth with and without autism spectrum
      disorder facing surgery varied by reporter and setting, highlighting the
      importance of using multiple reporters in research of youth with autism spectrum
      disorder in the perioperative period. Furthermore, while results showed group
      differences in premedication patterns and induction compliance, groups did not
      differ in level of negative behavior change after surgery. Future research can
      examine how individual differences in youth with autism impact anxiety in the
      perioperative setting and degree of behavior change postprocedure.

PMID- 29226495
TI  - Forgetting to remember? Prospective memory within the context of pain.
AB  - BACKGROUND: Pain interferes with cognitive functioning in several ways. Among
      other symptoms, pain patients often report difficulties with remembering future
      intentions. It remains unclear, however, whether it is the pain per se that
      impairs prospective remembering or other factors that often characterize people
      with pain (e.g. poor sleep quality). In this experiment, we investigated whether
      prospective memory is impaired within the context of pain, and whether this
      impairment is enhanced when the threat value of pain is increased. METHODS:
      Healthy participants engaged in an ongoing word categorization task, during which
      they received either experimental pain stimuli (with or without threatening
      instructions designed to increase the threat value of pain), or no pain stimuli
      (no somatic stimuli and no threatening instructions). Crucially, participants
      were also instructed to perform a prospective memory intention on future moments
      that would be signalled by specific retrieval cues. RESULTS: Threatening
      instructions did not differentiate the pain groups in terms of pain threat value;
      therefore, we only focus on the difference between pain and no pain. Pain and no
      pain groups performed the prospective memory intention with similar frequency,
      indicating that prospective memory is not necessarily impaired when the intended
      action has to be performed in a painful context. CONCLUSIONS: Findings are
      discussed in the framework of the multiprocess theory of prospective memory,
      which differentiates between the spontaneous and the strategic retrieval of
      intentions. Methodological considerations and suggestions for future research are
      discussed. SIGNIFICANCE: This laboratory study combines established methods from
      two research fields to investigate the effects of a painful context on memory for
      future intentions. Painful context did not impair performance of a prospective
      memory intention that is assumed to be retrieved by means of spontaneous
      processing.

PMID- 29226491
TI  - Predictors and outcomes of heart failure with mid-range ejection fraction.
AB  - AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction
      (HFrEF) are well described, determinants and outcomes of heart failure with mid
      range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical
      and biochemical predictors of incident HFmrEF in the community. METHODS AND
      RESULTS: We pooled data from four community-based longitudinal cohorts, with
      ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction
      (EF) 41-49%], HFpEF (EF >=50%), and HFrEF (EF <=40%). Predictors of incident HF
      subtypes were assessed using multivariable Cox models. Among 28 820 participants
      free of HF followed for a median of 12 years, there were 200 new HFmrEF cases,
      compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included
      age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial
      infarction (multivariable adjusted P <= 0.003 for all). Biomarkers that predicted
      HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin
      (P <= 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF
      [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence
      interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for
      difference), and did not differ in their association with incident HFmrEF and
      HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality
      following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per
      1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000
      person-years, P = 0.78). CONCLUSIONS: We found overlap in predictors of incident
      HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse
      than HFpEF, and similar to HFrEF.

PMID- 29226496
TI  - Long-term in situ persistence of biodiversity in tropical sky islands revealed by
      landscape genomics.
AB  - Tropical mountains are areas of high species richness and endemism. Two
      historical phenomena may have contributed to this: (i) fragmentation and
      isolation of habitats may have promoted the genetic differentiation of
      populations and increased the possibility of allopatric divergence and speciation
      and (ii) the mountain areas may have allowed long-term population persistence
      during global climate fluctuations. These two phenomena have been studied using
      either species occurrence data or estimating species divergence times. However,
      only few studies have used intraspecific genetic data to analyse the mechanisms
      by which endemism may emerge at the microevolutionary scale. Here, we use
      landscape analysis of genomic SNP data sampled from two high-elevation plant
      species from an archipelago of tropical sky islands (the Trans-Mexican Volcanic
      Belt) to test for population genetic differentiation, synchronous demographic
      changes and habitat persistence. We show that genetic differentiation can be
      explained by the degree of glacial habitat connectivity among mountains and that
      mountains have facilitated the persistence of populations throughout
      glacial/interglacial cycles. Our results support the ongoing role of tropical
      mountains as cradles for biodiversity by uncovering cryptic differentiation and
      limits to gene flow.

PMID- 29226498
TI  - Dicarboxylic Acid Separation by Dynamic and Size-Matched Recognition in Solution
      and in the Solid State.
AB  - Bis(trimethylammonium) alkane diiodides dynamically encapsulate dicarboxylic
      acids through intermolecular hydrogen bonds between the I- anions of the hosts
      and the carboxylic OH groups of the guests. A selective recognition is realized
      when the size of the I- ???HOOC(CH2 /CF2 )n COOH???I- superanion matches the
      dication alkyl chain length. Dynamic recognition is also demonstrated in
      solution, where the presence of the size-matching organic salt boosts the acid
      solubility profile, thus allowing efficient mixture separation.

PMID- 29226497
TI  - Similar outcome of allogeneic stem cell transplantation after myeloablative and
      sequential conditioning regimen in patients with refractory or relapsed acute
      myeloid leukemia: A study from the Societe Francophone de Greffe de Moelle et de
      Therapie Cellulaire.
AB  - Patients with acute myeloid leukemia (AML) in relapse or refractory to induction
      therapy have a dismal prognosis. Allogeneic hematopoietic stem cell
      transplantation is the only curative option. In these patients, we aimed to
      compare the results of a myeloablative transplant versus a sequential approach
      consisting in a cytoreductive chemotherapy followed by a reduced intensity
      conditioning regimen and prophylactic donor lymphocytes infusions. We
      retrospectively analyzed 99 patients aged 18-50 years, transplanted for a
      refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients
      received a sequential approach and 41 patients a myeloablative conditioning
      regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With
      a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence
      interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in
      the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR)
      was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in
      the myeloablative group (17% versus 15%, P = .44). In multivariate analysis,
      overall survival, CIR and nonrelapse mortality remained similar between the two
      groups. However, in multivariate analysis, sequential conditioning led to fewer
      acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach =
      0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD
      (all grades and extensive). In young patients with refractory or relapsed AML,
      myeloablative transplant and sequential approach offer similar outcomes except
      for a lower incidence of acute GvHD after a sequential transplant.

PMID- 29226499
TI  - Thioketone-Directed Palladium(II)-Catalyzed C-H Arylation of Ferrocenes with Aryl
      Boronic Acids.
AB  - A palladium(II)-catalyzed thioketone-chelation-assisted direct C-H arylation of
      ferrocenes is described. With thioketone as an efficient directing group, various
      monoaryl- and diaryl-substituted thiocarbonylferrocenes were obtained by
      palladium-catalyzed direct C-H functionalization in high yields under mild and
      base-free reaction conditions. Furthermore, the arylated thiocarbonylferrocene
      could undergo diverse transformations.

PMID- 29226500
TI  - Anti-inflammatory effects of propranolol in the temporomandibular joint of female
      rats and its contribution to antinociceptive action.
AB  - BACKGROUND: beta-Blockers reduce temporomandibular joint (TMJ) pain. We asked
      whether they also reduce TMJ inflammation and, if so, whether this anti
      inflammatory effect contributes to its analgesic action. METHODS: We measured
      many parameters of the inflammatory response after co-administration of the beta
      blocker propranolol with the inflammatory agent carrageenan in the TMJ of female
      rats. We also hypothesized that the activation of beta-adrenoceptors in the TMJ
      induces nociception mediated, at least in part, by the inflammatory response. To
      test this hypothesis, we examined the nociceptive response induced by the
      activation of the beta-adrenoceptors in the TMJ in female rats pretreated with
      thalidomide and fucoidan. RESULTS: We found that the co-administration of
      propranolol with carrageenan in the TMJ of female rats significantly reduced
      several parameters of the inflammatory response induced by carrageenan such as
      plasma extravasation, neutrophil migration and the release of the pro
      inflammatory cytokines TNF-alpha, IL-1beta and CINC-1. Furthermore, the injection
      of the beta-adrenergic receptor agonist isoproterenol in the TMJ induced
      nociception that was significantly reduced by thalidomide, fucoidan and by the co
      administration of propranolol but not of the alpha-adrenergic receptor antagonist
      phentolamine. CONCLUSIONS: Propranolol has anti-inflammatory effects that
      contribute to its antinociceptive action in the TMJ of females. SIGNIFICANCE:
      beta-Blockers have an anti-inflammatory effect on temporomandibular joint (TMJ)
      that contributes to its analgesic effect. The results of this work suggest that
      beta-blockers can be used to treat the painful conditions of TMJ, especially when
      they are associated with an inflammatory process.

PMID- 29226501
TI  - Drop-On-Drop Multimaterial 3D Bioprinting Realized by Peroxidase-Mediated Cross
      Linking.
AB  - A cytocompatible inkjet bioprinting approach that enables the use of a variety of
      bioinks to produce hydrogels with a wide range of characteristics is developed.
      Stabilization of bioinks is caused by horseradish peroxidase (HRP)-catalyzed
      cross-linking consuming hydrogen peroxide (H2 O2 ). 3D cell-laden hydrogels are
      fabricated by the sequential dropping of a bioink containing polymer(s) cross
      linkable through the enzymatic reaction and H2 O2 onto droplets of another bioink
      containing the polymer, HRP, and cells. The ~95% viability of enclosed mouse
      fibroblasts and subsequent elongation of the cells in a bioprinted hydrogel
      consisting of gelatin and hyaluronic acid derivatives suggest the high
      cytocompatibility of the developed printing approach. The existence of numerous
      polymers, including derivatives of polysaccharides, proteins, and synthetic
      polymers, cross-linkable through the HRP-catalyzed reaction, means the current
      approach shows great promise for biofabrication of functional and structurally
      complex tissues.

PMID- 29226502
TI  - S-R difference in V1-V2 is a novel criterion for differentiating the left from
      right ventricular outflow tract arrhythmias.
AB  - AIM: The correct estimation of the VA origin as RVOT or LVOT results in reduced
      ablation duration reduced radiation exposure and decreased number of vascular
      access. In our study, we aimed to detect the predictive value of S-R difference
      in V1-V2 for differentiating the left from right ventricular outflow tract
      arrhythmias. METHODS: We included 123 patients with symptomatic frequent
      premature ventricular outflow tract contractions who underwent successful
      catheter ablation (70 male, 53 female; mean age 46.2 +/- 13.9 years, 61 RVOT, 62
      LVOT origins). S-R difference in V1-V2 was calculated with this formula on the 12
      lead surface ECG: (V1S + V2S) - (V1R + V2R). Conventional ablation was performed
      in 101 (82.1%) patients, CARTO electroanatomic mapping system was used in 22
      (17.9%) patients. RESULTS: V1-2 SRd was found to be significantly lower for LVOT
      origins than RVOT origins (p < .001). The cutoff value of V1-2 SRd obtained by
      ROC curve analysis was 1.625 mV for prediction of RVOT origin (sensitivity:
      95.1%, specificity: 85.5%, positive predictive value: 86.5%, negative predictive
      value: 94.5%). The area under the curve (AUC) was 0.929 (p < .001). CONCLUSION: S
      R difference in V1-V2 is a novel and simple electrocardiographic criterion for
      accurately differentiating RVOT from LVOT sites of ventricular arrhythmia
      origins. The use of this simple ECG measurement could improve the accuracy of
      OTVA localization, could be beneficial for decreasing ablation duration and
      radiation exposure. Further studies with larger patient population are needed to
      verify the results of this study.

PMID- 29226503
TI  - Development, characterization, and evaluation of sunscreen cream containing solid
      lipid nanoparticles of silymarin.
AB  - BACKGROUND: Most of the sunscreen formulations mainly contain chemicals or
      synthetic molecules. Nowadays, researchers are mainly focussing on herbal
      formulations due to toxicity of the synthetic molecules. Silymarin is a natural
      flavonoids having excellent antioxidant properties. Solid lipid nanoparticles are
      novel drug carriers which improve the drug stability and tolerance effect and
      also enhance the permeation effect. AIMS: This study aimed at the preparation of
      solid lipid nanoparticles containing silymarin that will be incorporated into a
      sunscreen cream and determine its sun protection factor. METHODS: The solid lipid
      nanoparticles were prepared by micro-emulsion method; here, the glyceryl
      monostearate was used as lipid, and Tween 80 was used as an emulsifier. The solid
      lipid nanoparticles were evaluated for drug entrapment, particle size and
      morphology, zeta potential, and polydispersity index. The dispersion was
      formulated into sunscreen cream and evaluated for various parameters, such as
      extrudability, viscosity, spreadability, drug content, in vitro drug release, ex
      vivo permeation of drug, in vitro and in vivo sun protection factor
      determination, in vivo skin irritation test, and accelerated stability studies.
      RESULTS: The results suggested that as the concentration of emulsifier increased,
      the entrapment efficiency of silymarin increased. In vitro and in vivo sun
      protection factor determination showed that SPF of 13.80 and 14.1, respectively.
      Stability studies were performed under accelerated conditions, and it did not
      show any appreciable change in parameters. CONCLUSION: These results indicated
      that the sunscreen containing silymarin solid lipid nanoparticles exhibited
      better photoprotective action.

PMID- 29226504
TI  - Metacognitive beliefs as a predictor of health anxiety in a self-reporting
      Italian clinical sample.
AB  - Research has supported the specific role that anxiety sensitivity, health-related
      dysfunctional beliefs, and metacognitive beliefs may play in the development and
      maintenance of health anxiety symptoms. However, the role of metacognitive
      beliefs in health anxiety has only been explored in analogue samples. The aim of
      this study was to explore for the first time the association between
      metacognitive beliefs and health anxiety symptoms in a sample of participants who
      reported having received a diagnosis of severe health anxiety (hypochondriasis)
      or illness anxiety disorder and test whether these beliefs are significant
      predictors of health anxiety after controlling for anxiety, depression, anxiety
      sensitivity, and dysfunctional beliefs. A series of dimensional self-report
      measures were administered to a large Italian sample (N = 458). At a bivariate
      level, Beliefs that Thoughts are Uncontrollable had a stronger association with
      health anxiety than any of the dysfunctional beliefs and anxiety sensitivity
      subscales. Results from hierarchical multiple regression analysis indicated that
      Beliefs that Thoughts are Uncontrollable predicted health anxiety symptoms over
      and-above depression, general anxiety, anxiety sensitivity, and health-related
      dysfunctional beliefs. Despite many important limitations, this study supported
      the hypothesis that metacognition may have an important role in health anxiety in
      clinical samples.

PMID- 29226505
TI  - Evaluating the Association between Enlarged Perivascular Spaces and Disease
      Worsening in Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVSs) have been associated
      with relapses and brain atrophy in multiple sclerosis (MS). We investigated the
      association of EPVS with clinical and MRI features of disease worsening in a well
      characterized cohort of relapsing-remitting MS patients prospectively followed
      for up to 10 years. METHODS: Baseline EPVSs were scored on 1.5T MRI in 30
      converters to moderate-severe disability, and 30 nonconverters matched for
      baseline characteristics. RESULTS: EPVS scores were not significantly different
      between converters and nonconverters, nor associated with accrual of lesions or
      brain atrophy. CONCLUSIONS: Our preliminary findings from a relatively small
      study sample argue against a potential use of EPVS as early indicator of risk for
      disease worsening in relapsing-remitting MS patients in a clinical setting.
      Although the small sample size and clinical 1.5T MRI may have limited our ability
      to detect a significant effect, we provided estimates of the association of EPVS
      with clinical and MRI indicators of disease worsening in a well-characterized
      cohort of MS patients.

PMID- 29226506
TI  - Optimizing hemodynamics of transcatheter aortic valve-in-valve implantation in 19
      mm surgical aortic prostheses.
AB  - OBJECTIVE: To demonstrate the feasibility of achieving good hemodynamic results
      with valve-in-valve transcatheter aortic valve replacement (ViV TAVR) for
      degenerated 19 mm surgical bioprosthetic valves. BACKGROUND: Considerable
      controversy exists regarding ViV TAVR within 19mm surgical prostheses due to
      concerns of elevated valve gradients and mortality. METHODS: Among all patient
      undergoing ViV TAVR between 7/2016 and 4/2017 for symptomatic severe
      bioprosthetic aortic stenosis (AS), five had a 19 mm surgical valve in place and
      were included in this publication. None of the patients had patient-prosthesis
      mismatch. Aggressive post-dilation was performed in four out of five cases using
      a special technique we describe below. RESULTS: In all cases, mean aortic valve
      (AV) gradients significantly improved post-ViV TAVR, particularly after post
      dilation. Interestingly, high pressure post-dilation of the ViV resulted in an
      increase in the diameter of surgical valve stent frame dimensions in nearly all
      patients who underwent post-dilation. CONCLUSIONS: Good hemodynamic outcome is
      possible with aggressive post-dilation in patients with 19 mm failed surgical
      bioprostheses. High-risk patients with 19 mm failed surgical prostheses who do
      not otherwise have viable surgical options should be considered for ViV TAVR.

PMID- 29226507
TI  - Age is a predictor of a small decrease in lung function in children with sickle
      cell anemia.
AB  - The longitudinal pattern of lung function in children with sickle cell anemia
      (SCA) has shown a decrease in FEV1 % predicted, a risk factor for death in adults
      with SCA, but predictors for this decline are poorly characterized. In a
      prospective longitudinal multi-center cohort of children with SCA, we tested the
      hypotheses that: (1) FEV1 % predicted declines over time; and (2) SCA-specific
      characteristics and therapy predict this decline. At three clinical centers,
      children with SCA (HbSS or HbSbeta0 thalassemia), unselected for respiratory
      disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study
      certified pulmonary function technicians performed spirometry and lung volumes.
      Each assessment was reviewed centrally. Predicted values were determined for TLC,
      FEV1 , FVC, and FEV1 /FVC ratio. A total of 197 participants, mean age 11.0 years
      at first testing (range 4-19.3 years), had a minimum of three spirometry
      measurements, over an average of 4.4 years (range 1.1-6.5 years) from baseline to
      endpoint. In a multivariable model, FEV1 % predicted declines by 0.3% for every
      additional year of age (95% CI -0.56 to -0.05, P = .020). Sex, asthma history,
      hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe
      acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not
      associated with a decline in FEV1 % predicted. In a large, rigorously evaluated,
      prospective cohort of an unselected group of children with SCA, FEV1 % predicted
      declines minimally over an average of 4 years, and none of the examined disease
      features predict the decline.

PMID- 29226508
TI  - Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation
      and puncture in mice.
AB  - Sepsis is associated with high mortality. Both critically ill humans and animal
      models of sepsis exhibit changes in their glucose homeostasis, that is,
      hypoglycaemia, with the progression of infection. However, the relationship
      between basal glycaemia, glucose tolerance and insulin sensitivity is not well
      understood. Thus, we aimed to evaluate this glucose homeostasis triad at the late
      stage of sepsis (24 h after surgery) in male Swiss mice subjected to lethal and
      sublethal sepsis by the caecal ligation and puncture (CLP) model. The percentage
      of survival 24 h after CLP procedure in the Lethal and Sublethal groups was
      around 66% and 100% respectively. Both Lethal and Sublethal groups became
      hypoglycaemic in fasting and fed states 24 h after surgery. The pronounced fed
      hypoglycaemia in the Lethal group was not due to worsening anorexic behaviour or
      hepatic inability to deliver glucose in relation to the Sublethal group.
      Reduction in insulin sensitivity in CLP mice occurred in a lethality-dependent
      manner and was not associated with glucose intolerance. Analysis of oral and
      intraperitoneal glucose tolerance tests, as well as the gastrointestinal motility
      data, indicated that CLP mice had reduced intestinal glucose absorption.
      Altogether, we suggest cessation of appetite and intestinal glucose malabsorption
      are key contributors to the hypoglycaemic state observed during experimental
      severe sepsis.

PMID- 29226509
TI  - Biomimetic electrospun coatings increase the in vivo sensitivity of implantable
      glucose biosensors.
AB  - In vivo tissue responses and functional efficacy of electrospun membranes based
      on polyurethane (PU) and gelatin (GE) as biomimetic coatings for implantable
      glucose biosensors was investigated in a rat subcutaneous implantation model.
      Three electrospun membranes with optimized fiber diameters, pore sizes, and
      permeability, both single PU and coaxial PU-GE fibers and a solvent cast PU film
      were implanted in rats to evaluate tissue responses. For functional efficacy
      testing, four sensor variants coated with the above mentioned electrospun
      membranes as mass-transport limiting and outermost biomimetic coatings were
      implanted in rats. The electrospun PU membranes had micron sized pores that were
      not permeable to host cells when implanted in the body. However, PU-GE coaxial
      fiber membranes, having similar sized pores, were infiltrated with fibroblasts
      that deposited collagen in the membrane's pores. Such tissue response prevented
      the formation of dense fibrous capsule around the sensor coated with the PU-GE
      coaxial fiber membranes, which helped improve the in vivo sensitivity for at
      least 3 weeks compared to the traditional sensors in rat subcutaneous tissue.
      Furthermore, the better in vitro sensor's sensitivity due to electrospun PU as
      the mass-transport limiting membrane translated to better in vivo sensitivity.
      Thus, this study showed that electrospun membranes can play an important role in
      realizing long in vivo sensing lifetime of implantable glucose biosensors. (c)
      2017 The Authors Journal of Biomedical Materials Research Part A Published by
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1072-1081, 2018.

PMID- 29226510
TI  - Authors' reply re: Inositol treatment of anovulation in women with polycystic
      ovary syndrome: a meta-analysis of randomised trials.

PMID- 29226511
TI  - Differentiation of isomeric methylanilines by imidization and gas
      chromatography/mass spectrometry analysis.
AB  - RATIONALE: Carcinogenic o-methylaniline is one of the banned aromatic amines in
      azo dyes, but it is very difficult to distinguish it from its noncarcinogenic
      isomers due to their identical retention time on chromatography and similar mass
      spectra. METHODS: Imidization of the isomeric methylanilines was carried out by
      treatment with benzaldehyde under mild conditions. The formed derivatives were
      analyzed by gas chromatography/mass spectrometry (GC/MS). Theoretical
      calculations were carried out on the Gaussian 03 program by using the density
      functional theory method at the B3LYP/6-311+G(d,p) level. RESULTS: Imidization of
      methylanilines occurred easily and gave rise to the corresponding N
      methylbenzylidene benzenamines. The isomeric derivatives were completely
      separated by GC, and thus the three isomeric methylanilines could be determined
      simultaneously. Due to the ortho effect, the derivative from o-methylaniline has
      a characteristic fragment ion at m/z 118 with a stable bicyclic structure, and it
      could be easily differentiated from the meta- and para-isomers in electron
      ionization mass spectrometry. CONCLUSIONS: These results provided a promising
      solution for simultaneous determination of isomeric methylanilines.

PMID- 29226512
TI  - Diagnosis of vertical root fractures in endodontically treated teeth utilising
      Digital Subtraction Radiography: A case series report.
AB  - Vertical root fractures are commonly associated with root-filled teeth. Diagnosis
      is challenging because the clinical signs are not completely pathognomonic, and
      conventional periapical radiography is often unreliable. Digital subtraction
      radiography (DSR) is able to detect small radiographic changes between two
      successive radiographs by subtracting out consistent radiographic elements. Its
      use could possibly assist in the diagnostic procedure. Four cases are presented
      to demonstrate the potential use of DSR in the detection of vertical root
      fractures in endodontically treated teeth. After the digital subtractions had
      been carried out, a dark line in the body of the roots was distinguishable,
      raising the possibility of the presence of a vertical root fracture. The use of
      contrast enhancement and pseudocolouring techniques assisted with the diagnosis
      of vertical root fractures. DSR proved to be a useful diagnostic tool for the
      detection of vertical root fractures in these four clinical cases.

PMID- 29226513
TI  - Consolidation of vocabulary is associated with sleep in typically developing
      children, but not in children with dyslexia.
AB  - Sleep is known to play an active role in consolidating new vocabulary in adults;
      however, the mechanisms by which sleep promotes vocabulary consolidation in
      childhood are less well understood. Furthermore, there has been no investigation
      into whether previously reported differences in sleep architecture might account
      for variability in vocabulary consolidation in children with dyslexia. Twenty
      three children with dyslexia and 29 age-matched typically developing peers were
      exposed to 16 novel spoken words. Typically developing children showed overnight
      improvements in novel word recall; the size of the improvement correlated
      positively with slow wave activity, similar to previous findings with adults.
      Children with dyslexia showed poorer recall of the novel words overall, but
      nevertheless showed overnight improvements similar to age-matched peers. However,
      comparisons with younger children matched on initial levels of novel word recall
      pointed to reduced consolidation in dyslexics after 1 week. Crucially, there were
      no significant correlations between overnight consolidation and sleep parameters
      in the dyslexic group. This suggests a reduced role of sleep in vocabulary
      consolidation in dyslexia, possibly as a consequence of lower levels of learning
      prior to sleep, and highlights how models of sleep-associated memory
      consolidation can be usefully informed by data from typical and atypical
      development.

PMID- 29226514
TI  - Hospital admission in children and adolescents with or without type 1 diabetes
      from Germany: An analysis of statutory health insurance data on 12 million
      subjects.
AB  - OBJECTIVE: To compare the chance of hospital admissions in children and
      adolescents with type 1 diabetes (T1D) to that without T1D from Germany. METHODS:
      Data were provided by the German information system for health care data which
      contains information on all patients with a statutory health insurance. The years
      2009 and 2011 were considered. Children and adolescents (0 to <=19 years of age;
      n = 12 030 242) were included. Unadjusted odds ratios (ORs) with 95% confidence
      interval (95% CI) were used to compare the hospitalization rate for patients with
      (n = 26 444) or without T1D (12 003 798). T1D was identified by documented
      insulin treatment and by ICD-code E10/14. Results were stratified by age-group (0
      5; >5-10; >10-15, >15-19 years) and gender. RESULTS: In all age-groups, the
      hospitalization chance in patients with T1D was higher compared to that of their
      peers (database 2011). The highest OR was observed in >5 to 10-year-old patients
      (OR 8.1; 95% CI: 7.7-8.5), followed by patients >10 to 15 years (OR 7.4; 95% CI:
      7.1-7.7) and patients <=5 years (OR 5.3; 95% CI: 4.8-5.7). The lowest OR was
      present in patients >15 to 19 years (OR 4.0; 95% CI: 3.9-4.2). Overall, OR for
      hospital admission were higher in girls with T1D compared to boys. The most
      frequent reasons for hospitalization in T1D were "T1D without complications"
      (68.4%) and "T1D with ketoacidosis" (18.6%). CONCLUSIONS: Children and
      adolescents with T1D in Germany had a 4 to 8 times higher hospitalization chance
      compared to children without T1D. The OR in T1D patients compared to peers were
      higher in girls than in boys. High rates of elective hospital admission in
      Germany may contribute to these results.

PMID- 29226515
TI  - Surface Strain Redistribution on Structured Microfibers to Enhance Sensitivity of
      Fiber-Shaped Stretchable Strain Sensors.
AB  - Fiber-shaped stretchable strain sensors with small testing areas can be directly
      woven into textiles. This paves the way for the design of integrated wearable
      devices capable of obtaining real-time mechanical feedback for various
      applications. However, for a simple fiber that undergoes uniform strain
      distribution during deformation, it is still a big challenge to obtain high
      sensitivity. Herein, a new strategy, surface strain redistribution, is reported
      to significantly enhance the sensitivity of fiber-shaped stretchable strain
      sensors. A new method of transient thermal curing is used to achieve the large
      scale fabrication of modified elastic microfibers with intrinsic microbeads. The
      proposed strategy is independent of the active materials utilized and can be
      universally applied for various active materials. The strategy used here will
      shift the vision of the sensitivity enhancement method from the active materials
      design to the mechanical design of the elastic substrate, and the proposed
      strategy can also be applied to nonfiber-shaped stretchable strain sensors.

PMID- 29226516
TI  - SOST, an LNGFR target, inhibits the osteogenic differentiation of rat
      ectomesenchymal stem cells.
AB  - OBJECTIVES: The aim of this study was to investigate whether sclerostin (SOST)
      regulates the osteogenic differentiation of rat ectomesenchymal stem cells
      (EMSCs) and whether SOST and low-affinity nerve growth factor receptor (LNGFR)
      regulate the osteogenic differentiation of EMSCs. MATERIALS AND METHODS: EMSCs
      were isolated from embryonic facial processes from an embryonic 12.5-day (E12.5d)
      pregnant Sprague-Dawley rat. LNGFR+ EMSCs and LNGFR- EMSCs were obtained by
      fluorescence-activated cell sorting and were subsequently induced to undergo
      osteogenic differentiation in vitro. SOST/LNGFR small-interfering RNAs and
      SOST/LNGFR overexpression plasmids were used to transfect EMSCs. RESULTS: LNGFR+
      EMSCs displayed a higher osteogenic capacity and lower SOST levels compared with
      LNGFR- EMSCs. SOST silencing enhanced the osteogenic differentiation of LNGFR-
      EMSCs, while SOST overexpression attenuated the osteogenic differentiation of
      LNGFR+ EMSCs. Moreover, LNGFR was present upstream of SOST and strengthened the
      osteogenic differentiation of EMSCs by decreasing SOST. CONCLUSIONS: SOST
      alleviated the osteogenic differentiation of EMSCs, and LNGFR enhanced the
      osteogenic differentiation of EMSCs by decreasing SOST, suggesting that the
      LNGFR/SOST pathway may be a novel target for promoting dental tissue regeneration
      and engineering.

PMID- 29226517
TI  - Natural selection beyond genes: Identification and analyses of evolutionarily
      conserved elements in the genome of the collared flycatcher (Ficedula
      albicollis).
AB  - It is becoming increasingly clear that a significant proportion of the functional
      sequence within eukaryotic genomes is noncoding. However, since the
      identification of conserved elements (CEs) has been restricted to a limited
      number of model organisms, the dynamics and evolutionary character of the genomic
      landscape of conserved, and hence likely functional, sequence is poorly
      understood in most species. Moreover, identification and analysis of the full
      suite of functional sequence are particularly important for the understanding of
      the genetic basis of trait loci identified in genome scans or quantitative trait
      locus mapping efforts. We report that ~6.6% of the collared flycatcher genome
      (74.0 Mb) is spanned by ~1.28 million CEs, a higher proportion of the genome but
      a lower total amount of conserved sequence than has been reported in mammals. We
      identified >200,000 CEs specific to either the archosaur, avian, neoavian or
      passeridan lineages, constituting candidates for lineage-specific adaptations.
      Importantly, no less than ~71% of CE sites were nonexonic (52.6 Mb), and
      conserved nonexonic sequence density was negatively correlated with functional
      exonic density at local genomic scales. Additionally, nucleotide diversity was
      strongly reduced at nonexonic conserved sites (0.00153) relative to intergenic
      nonconserved sites (0.00427). By integrating deep transcriptome sequencing and
      additional genome annotation, we identified novel protein-coding genes, long
      noncoding RNA genes and transposon-derived (exapted) CEs. The approach taken here
      based on the use of a progressive cactus whole-genome alignment to identify CEs
      should be readily applicable to nonmodel organisms in general and help to reveal
      the rich repertoire of putatively functional noncoding sequence as targets for
      selection.

PMID- 29226518
TI  - Acceptability and benefit of rectal irrigation in patients with Low Anterior
      Resection Syndrome: a qualitative study.
AB  - AIM: Low Anterior Resection Syndrome (LARS) following rectal cancer surgery
      impairs the patient's quality of life (QoL). Rectal Irrigation has been
      demonstrated to be effective for anterior resection syndrome but many surgeons do
      not suggest it as a treatment. This feasibility study aimed to explore treatment
      acceptability and the benefit of rectal irrigation in patients who developed LARS
      following an anterior resection for rectal cancer. METHODS: This was a
      qualitative study, involving semi-structured interviews. Twenty-one patients
      diagnosed with LARS following anterior resection for rectal cancer in a single
      tertiary centre were offered rectal irrigation as a treatment option. Qualitative
      interviews (n=17) were conducted at baseline to explore patient reported impact
      of LARS on QoL, treatment acceptability and factors influencing the decision to
      accept/decline treatment. Follow up interviews were carried out at six months for
      the treatment group only (n=12), to assess its practicality and impact on QoL.
      RESULTS: Qualitative interview findings suggest rectal irrigation is an
      acceptable method of treatment for LARS. Participants who perceived their
      symptoms to be more severe or poorly controlled were most likely to consider
      rectal irrigation as a treatment option. The patients who completed treatment
      reported improvements in their QoL, the ability to control the time of
      defaecation being the key benefit CONCLUSION: Clinicians should consider offering
      rectal irrigation as a treatment option to patients presenting with bowel
      dysfunction following anterior resection as it can improve symptoms. Patients who
      perceive that their symptoms are severe are more likely to consider treatment.
      This article is protected by copyright. All rights reserved.

PMID- 29226519
TI  - Cripto stabilizes GRP78 on the cell membrane.
AB  - The ER resident chaperone molecule GRP78 has been shown to translocate to the
      cell surface where it associates with Cripto and signals cell growth, playing a
      still partially understood role in tumorigenesis. Consequently, a better
      understanding of GRP78 topology and structure at the surface of cancer cells
      represents an important step in the development of a new class of therapeutics.
      Here, we used a set of programs for creation of a complex containing GRP78 and
      Cripto proteins. We elucidated possible interactions of GRP78, Cripto, and their
      complex with the membrane. Using molecular dynamics simulations, we demonstrated
      that Cripto binding to GRP78 completely changes the dynamics of its behavior on
      the membrane, not allowing GRP78 to disconnect from it, thus enabling GRP78
      tumorigenic functions.

PMID- 29226520
TI  - A novel homozygous SLC25A1 mutation with impaired mitochondrial complex V:
      Possible phenotypic expansion.
AB  - SLC25A1 mutations are associated with combined D,L-2-hydroxyglutaric aciduria (DL
      2HGA; OMIM #615182), characterized by muscular hypotonia, severe
      neurodevelopmental dysfunction and intractable seizures. SLC25A1 encodes the
      mitochondrial citrate carrier (CIC), which mediates efflux of the mitochondrial
      tricarboxylic acid (TCA) cycle intermediates citrate and isocitrate in exchange
      for cytosolic malate. Only a single family with an SLC25A1 mutation has been
      described in which mitochondrial respiratory chain dysfunction was documented,
      specifically in complex IV. Five infants of two consanguineous Bedouin families
      of the same tribe presented with small head circumference and neonatal-onset
      encephalopathy with severe muscular weakness, intractable seizures, respiratory
      distress, and lack of psychomotor development culminating in early death.
      Ventricular septal defects (VSD) were demonstrated in three patients. Blood and
      CSF lactate were elevated with normal levels of plasma amino acids and free
      carnitine and increased 2-OH-glutaric acid urinary exertion. EEG was compatible
      with white matter disorder. Brain MRI revealed ventriculomegaly, thin corpus
      callosum with increased lactate peak on spectroscopy. Mitochondrial complex V
      deficiency was demonstrated in skeletal muscle biopsy of one infant. Homozygosity
      mapping and sequencing ruled out homozygosity of affected individuals in all
      known complex V-associated genes. Whole exome sequencing identified a novel
      homozygous SLC25A1 c.713A>G (p.Asn238Ser) mutation, segregating as expected in
      the affected kindred and not found in 220 control alleles. Thus, SLC25A1
      mutations might be associated with mitochondrial complex V deficiency and should
      be considered in the differential diagnosis of mitochondrial respiratory chain
      defects.

PMID- 29226521
TI  - The ontogeny of the female reproductive system in the parasitic castrator pea
      crab Calyptraeotheres garthi: Implications for its mating system.
AB  - The knowledge of the mating system of pea crabs is still fragmentary as it
      remains dubious whether females copulate in the juvenile and free-living 'hard'
      or in the obligatory symbiotic stages (adult stage 'V' or intermediate stages II
      to IV). To discriminate between these two possibilities, we analysed the female
      seminal receptacles, vagina and opercula, and the sperm content in different
      stages of the pea crab Calyptraeotheres garthi. Our histology and scanning
      electron microscopy results revealed that in the hard stage the seminal
      receptacle is simple without secretory epithelia, and vagina and opercula are not
      controlled by musculature. In stages II to IV, the seminal receptacles, vagina,
      and opercula are under development and these structures reach maturity in stage
      V. These results suggest that females become receptive in stage V and not during
      predating stages. We found no spermatozoa in SR of 'hard' and stage II to IV
      females while these structures were loaded of sperm in most stage V, indicating
      that females start to mate in stage V. Our results support the notion that males
      of C. garthi roam among hosts in search for sedentary stage V females, as
      predicted by Baeza and Thiel's () model of mating systems for symbiotic
      crustaceans. Nevertheless, we failed to reveal whether females mate repeatedly:
      the accumulation of sperm in larger females might indicate occurrence of multiple
      copula or a high variability in male sperm transfer.

PMID- 29226523
TI  - A Single-Step Hydrothermal Route to 3D Hierarchical Cu2 O/CuO/rGO Nanosheets as
      High-Performance Anode of Lithium-Ion Batteries.
AB  - As anodes of Li-ion batteries, copper oxides (CuO) have a high theoretical
      specific capacity (674 mA h g-1 ) but own poor cyclic stability owing to the
      large volume expansion and low conductivity in charges/discharges. Incorporating
      reduced graphene oxide (rGO) into CuO anodes with conventional methods fails to
      build robust interaction between rGO and CuO to efficiently improve the overall
      anode performance. Here, Cu2 O/CuO/reduced graphene oxides (Cu2 O/CuO/rGO) with a
      3D hierarchical nanostructure are synthesized with a facile, single-step
      hydrothermal method. The Cu2 O/CuO/rGO anode exhibits remarkable cyclic and high
      rate performances, and particularly the anode with 25 wt% rGO owns the best
      performance among all samples, delivering a record capacity of 550 mA h g-1 at
      0.5 C after 100 cycles. The pronounced performances are attributed to the highly
      efficient charge transfer in CuO nanosheets encapsulated in rGO network and the
      mitigated volume expansion of the anode owing to its robust 3D hierarchical
      nanostructure.

PMID- 29226522
TI  - ZEB1-AS1: A crucial cancer-related long non-coding RNA.
AB  - Long non-coding RNAs (lncRNAs) recently emerge as a novel class of non-coding
      RNAs (ncRNAs) with larger than 200 nucleotides in length. Due to lack an obvious
      open reading frame, lncRNAs have no or limited protein-coding potential. To date,
      accumulating evidence indicates the vital regulatory function of lncRNAs in
      pathological processes of human diseases, especially in carcinogenesis and
      development. Deregulation of lncRNAs not only alters cellular biological
      behavior, such as proliferation, migration and invasion, but also represents the
      poor clinical outcomes. Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1
      AS1), an outstanding cancer-related lncRNA, is identified as an oncogenic
      regulator in diverse malignancies. Dysregulation of ZEB1-AS1 has been
      demonstrated to exhibit a pivotal role in tumorigenesis and progression,
      suggesting its potential clinical value as a promising biomarker or therapeutic
      target for cancers. In this review, we make a summary on the current findings
      regarding the biological functions, underlying mechanisms and clinical
      significance of ZEB1-AS1 in cancer progression.

PMID- 29226524
TI  - Usefulness of virtual touch quantification for staging liver fibrosis in patients
      with hepatitis C, and factors affecting liver stiffness measurement failure
      compared with liver biopsy.
AB  - AIM: The assessment of liver fibrosis in patients with hepatitis C is important
      to predict carcinogenesis. In this study, we evaluated the usefulness of virtual
      touch quantification (VTQ) for staging liver fibrosis, and investigated factors
      causing discrepancies between the estimated fibrosis stage using VTQ and the
      pathological fibrosis stage. METHODS: Patients with hepatitis C (n = 302) were
      assessed using VTQ and underwent pathological liver investigation within 1 week
      before and after VTQ. A receiver operator characteristic (ROC) curve was obtained
      for VTQ, fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet
      ratio index (APRI), and each area under the ROC curve (AUROC) was compared to
      predict fibrosis stage. We used univariate and multivariate analyses to
      investigate the factors related to the discrepancy between the estimated fibrosis
      stage using VTQ and the pathological fibrosis stage. RESULTS: At any stage, VTQ
      was the most accurate for staging liver fibrosis. The VTQ cut-off values were
      1.33 m/s (AUROC = 0.822) for >=F2, 1.51 m/s (AUROC = 0.836) for >=F3, and 1.92
      m/s (AUROC = 0.890) for F4. Skin liver capsule distance (SCD) was the most
      relevant factor for the discrepancy between the estimated fibrosis stage using
      VTQ and the pathological fibrosis stage. The SCD cut-off value was 17.5 mm.
      CONCLUSIONS: Virtual touch quantification is a non-invasive, simple method that
      is more accurate for staging liver fibrosis than the FIB-4 index and APRI.
      However, when the SCD is longer than 17.5 mm, there may be measurement failures.

PMID- 29226525
TI  - In response to "Interventions designed using quality improvement methods reduce
      the incidence of serious airway events and airway cardiac arrests during
      pediatric anesthesia".

PMID- 29226526
TI  - We need personalized assessments for implicit bias in higher risk situations.

PMID- 29226527
TI  - What can we learn (or not) from in vitro airway studies for clinical applications
      in children?

PMID- 29226528
TI  - Mispositioning the end of a cuff inflating line in long-axis ultrasound imaging
      of the pediatric larynx and trachea.

PMID- 29226529
TI  - Continuous Erector Spinae Plane block for thoracic surgery in a pediatric
      patient.

PMID- 29226531
TI  - Pre-implant left ventricular apex position predicts risk of HeartMate II pump
      thrombosis.
AB  - BACKGROUND: Thrombosis within a left ventricular assist device (LVAD) is a
      devastating complication that often necessitates device exchange. Few studies
      have evaluated the relationship between patient anatomy and pump thrombosis. We
      hypothesize that lateral displacement of the left ventricular (LV) apex increases
      risk for pump thrombosis. METHODS: All patients who underwent primary
      implantation of a HeartMate II (HM2) device (Thoratec, Pleasanton, CA) at a
      single center (2009-2015) were evaluated. Operative mortalities and patients
      without imaging were excluded. The angle of the LV apex relative to the midline
      was measured on preoperative computed tomography scans by two independent
      surgeons. Pump thrombosis was defined as lactic dehydrogenase >700 with clinical
      symptoms of hemolysis or LVAD malfunction. Univariate and Cox Proportional
      Hazards analysis was performed to evaluate the impact of LV apex angle on long
      term freedom from pump exchange for thrombosis. RESULTS: Of 122 patients who met
      inclusion criteria for this study, 16 (13.1%) underwent exchange for presumed
      pump thrombosis. Of these patients, six (37.5%) required more than one exchange.
      Patients undergoing exchange for thrombosis had greater LV angle (43.8 +/- 9.7 vs
      49.5 +/- 11.2, p = 0.037) with LV apex angle being a significant predictor of
      LVAD exchange for thrombosis (hazard ratio = 1.047, P = 0.046). Additionally,
      when surgeon measurements were compared there was good inter-observer reliability
      (Pearson Correlation = 0.89). CONCLUSION: A laterally displaced left ventricular
      apex correlates with a higher risk of pump thrombosis in patients undergoing HM2
      implantation. LV apex angle is an easily obtained, reproducible measurement that
      should be considered when selecting a ventricular assist device.

PMID- 29226532
TI  - Low molecular weight heparin for the prevention of severe preeclampsia: where
      next?
AB  - Low molecular weight heparin has been extensively evaluated for the prevention of
      preeclampsia in high-risk pregnant women; however, the results from these trials
      have been conflicting. This review discusses the potential mechanisms of action
      of low molecular weight heparin for the prevention of severe preeclampsia, how to
      optimize the selection of high-risk women for participation in future trials, and
      the importance of trial standardization.

PMID- 29226534
TI  - Commentary on Urbanoski et al. (2018): Housing First and addiction-exploring the
      evidence.

PMID- 29226533
TI  - The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's
      Disease Associated Protein Kinase PINK1.
AB  - Mutations in PINK1, which impair its catalytic kinase activity, are causal for
      autosomal recessive early-onset Parkinson's disease (PD). Various studies have
      indicated that the activation of PINK1 could be a useful strategy in treating
      neurodegenerative diseases, such as PD. Herein, it is shown that the anthelmintic
      drug niclosamide and its analogues are capable of activating PINK1 in cells
      through the reversible impairment of the mitochondrial membrane potential. With
      these compounds, for the first time, it is demonstrated that the PINK1 pathway is
      active and detectable in primary neurons. These findings suggest that niclosamide
      and its analogues are robust compounds for the study of the PINK1 pathway and may
      hold promise as a therapeutic strategy in PD and related disorders.

PMID- 29226535
TI  - Commentary on Fraser et al. (2018): Evidence base for harm reduction services-the
      urban-rural divide.

PMID- 29226536
TI  - Commentary on Scheidell et al. (2018): En-counting adversities; the 'building
      blocks' of psychopathology.

PMID- 29226538
TI  - Erratum.

PMID- 29226537
TI  - Is 'hardcore smoker' a useful term in tobacco control?

PMID- 29226541
TI  - Introducing Addiction Lives.

PMID- 29226542
TI  - Spontaneous intramural duodenal hematoma as the manifestation of Noonan syndrome.

PMID- 29226543
TI  - Maternal immune activation in neurodevelopmental disorders.
AB  - Converging lines of evidence from basic science and clinical studies suggest a
      relationship between maternal immune activation (MIA) and neurodevelopmental
      disorders such as autism spectrum disorder (ASD) and schizophrenia. The
      mechanisms through which MIA increases the risk of neurodevelopmental disorders
      have become a subject of intensive research. This review aims to describe how
      dysregulation of microglial function and immune mechanisms may link MIA and
      neurodevelopmental pathologies. We also summarize the current evidence in animal
      models of MIA. Developmental Dynamics 247:588-619, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29226544
TI  - Single-Site AuI Catalyst for Silane Oxidation with Water.
AB  - Single-site Au anchored on mpg-C3 N4 (519 ppm Au loading) is developed as a
      highly active, selective, and stable catalyst for the oxidation of silanes with
      water with a turnover frequency as high as 50 200 h-1 , far exceeding most known
      catalysts based on total gold content. Other hydrosilanes bearing unsaturated
      functional groups also lead to corresponding silanols under mild reaction
      conditions without formation of any side products in good or excellent yields.
      The spherical aberration correction electron microscopy and extended X-ray
      absorption fine structure measurements both confirm the atomic dispersion of Au
      atoms stabilized by mpg-C3 N4 . The coordination of the catalytically active AuI
      by three nitrogen or carbon atoms in the tri-s-triazine repeating units not only
      prevents the Au atoms from aggregation, but also renders the surface AuI highly
      active, which is completely different than homogeneous AuI species.

PMID- 29226545
TI  - Nitrous oxide/oxygen mixture for analgesia in adult cancer patients with
      breakthrough pain: A randomized, double-blind controlled trial.
AB  - BACKGROUND: The aim of this study was to assess the efficacy of a fixed nitrous
      oxide/oxygen mixture for the management of breakthrough cancer pain.
      METHODS/DESIGN: A double-blind, placebo-controlled, randomized clinical trial was
      undertaken in the Medical ward of Tumor Hospital of General Hospital of Ningxia
      Medical University. 240 cancer patients with breakthrough pain were recruited and
      randomly received a standard pain treatment (morphine sulphate immediate release)
      plus a pre-prepared nitrous oxide/oxygen mixture, or the standard pain treatment
      plus oxygen. The primary endpoint measure was the numerical rating scale (NRS)
      score measured at baseline, 5 and 15 min after the beginning of treatment, and at
      5 min post treatment. RESULT: In all, analysis of pain score (NRS) at 5 min after
      the beginning of treatment shown a significant decrease in nitrous oxide/oxygen
      mixture treated patients with 2.8 +/- 1.3 versus 5.5 +/- 1.2 in controls (p <
      0.01). At 15 min during the intervention, the mean pain score for nitrous
      oxide/oxygen was 2.0 +/- 1.1 compared with 5.6 +/- 1.3 for oxygen (p < 0.01).
      CONCLUSION: This study shows that self-administered nitrous oxide/oxygen mixture
      was effective in reducing moderate to severe breakthrough pain among patients
      with cancer. SIGNIFICANCE: The management of breakthrough cancer pain is always a
      challenge due to its temporal characteristics of rapid onset, moderate to severe
      in intensity, short duration (median 30-60 min). Our study find that self
      administered nitrous oxide/oxygen mixture was effective in reducing moderate to
      severe breakthrough cancer pain.

PMID- 29226546
TI  - Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with
      a 15q26.3 deletion excluding the IGF1R gene.
AB  - Array comparative genomic hybridization is essential in the investigation of
      chromosomal rearrangements associated with epilepsy, intellectual disability, and
      dysmorphic features. In many cases deletions, duplications, additional marker
      chromosomes, and ring chromosomes originating from chromosome 15 lead to abnormal
      phenotypes. We present a child with epilepsy, cardiac symptoms, severely delayed
      mental and growth development, behavioral disturbances and characteristic
      dysmorphic features showing a ring chromosome 15 and a small supernumerary marker
      chromosome. Array CGH detected a 1 Mb deletion of 15q26.3 in a ring chromosome 15
      and a 2.6 Mb copy number gain of 15q11.2 corresponding to a small supernumerary
      marker chromosome involving proximal 15q. Our findings add to previously
      published results of 15q11q13 duplications and 15q26 terminal deletions. Based on
      our study we can support the previous reported limited information about the role
      of SELS, SNRPA1, and PCSK6 genes in the development of the heart morphology. On
      the other hand, we found that the copy number loss of our patient did not involve
      the IGF1R gene which is often associated with growth retardation (short stature
      and decreased weight). We hypothesize that haploinsufficiency of the 15q26
      genomic region distal to IGF1R gene might be related to growth disturbance;
      however, presence of the ring chromosome 15 itself could also be responsible for
      the growth delay.

PMID- 29226547
TI  - Avian embryonic coronary arterio-venous patterning involves the contribution of
      different endothelial and endocardial cell populations.
AB  - BACKGROUND: Coronary vasculature irrigates the myocardium and is crucial to late
      embryonic and adult heart function. Despite the developmental significance and
      clinical relevance of these blood vessels, the embryonic origin and the cellular
      and molecular mechanisms that regulate coronary arterio-venous patterning are not
      known in detail. In this study, we have used the avian embryo to dissect the
      ontogenetic origin and morphogenesis of coronary vasculature. RESULTS: We show
      that sinus venosus endocardial sprouts and proepicardial angioblasts pioneer
      coronary vascular formation, invading the developing heart simultaneously. We
      also report that avian ventricular endocardium has the potential to contribute to
      coronary vessels, and describe the incorporation of cardiac distal outflow tract
      endothelial cells to the peritruncal endothelial plexus to participate in
      coronary vascular formation. Finally, our findings indicate that large sinus
      venosus-independent sections of the forming coronary vasculature develop without
      connection to the systemic circulation and that coronary arterio-venous shunts
      form a few hours before peritruncal arterial endothelium connects to the aortic
      root. CONCLUSIONS: Embryonic coronary vasculature is a developmental mosaic,
      formed by the integration of vascular cells from, at least, four different
      embryological origins, which assemble in a coordinated manner to complete
      coronary vascular development. Developmental Dynamics 247:686-698, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29226548
TI  - Diffusion tensor imaging determines three-dimensional architecture of human
      cervix: a cross-sectional study.
AB  - OBJECTIVE: To determine the microarchitecture of the cervix using high-resolution
      diffusion tensor (DT) magnetic resonance imaging (MRI). DESIGN: Cross-sectional
      study. SETTING: Leeds, UK. SAMPLE: Women undergoing hysterectomy for benign
      pathology. METHODS: Ex-vivo DT-MRI measurements were obtained using a 9.4-T
      Bruker nuclear magnetic resonance (NMR) spectrometer on seven fixed human
      cervices obtained at hysterectomy. A deterministic fibre-tracking algorithm was
      used to indirectly visualise underlying fibre organisation. Inter-regional
      differences in tissue structure were sought using quantitative measurements of
      diffusion. MAIN OUTCOME MEASURE: The identification of an occlusive structure in
      the region corresponding to the internal cervical os. RESULTS: Fibre tracking
      demonstrated two regions: an outer circular and inner longitudinal layer. The
      total circumferential tract volume (TV) was greatest in the proximal region of
      the cervix (TV: proximal, 271 +/- 198 mm3 ; middle, 186 +/- 119 mm3 ; distal, 38
      +/- 36 mm3 ). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC)
      measurements were significantly different between regions in all samples (P <
      0.0005), indicating greater tract density and organisation towards the internal
      os. CONCLUSION: Fibre tracking infers a system of dense, well-defined, encircling
      fibres in the proximal region of the cervix, corresponding to the location of the
      internal os. These findings may provide evidence of specific anatomic
      microarchitecture within the cervix able to resist intrauterine forces associated
      with pregnancy. TWEETABLE ABSTRACT: Diffusion-tensor MRI derived tractography
      identified well-defined encircling fibres at the internal os.

PMID- 29226549
TI  - Fasting induces astroglial plasticity in the olfactory bulb glomeruli of rats.
AB  - The detection of food odors by the olfactory system, which plays a key role in
      regulating food intake and elaborating the hedonic value of food, is reciprocally
      influenced by the metabolic state. Fasting increases olfactory performance,
      notably by increasing the activity of olfactory bulb (OB) neurons. The
      glutamatergic synapses between olfactory sensory neurons and mitral cells in the
      OB glomeruli are regulated by astrocytes, periglomerular neurons, and centrifugal
      afferents. We compared the expansion of astroglial processes by quantifying GFAP
      labeled areas in fed and fasted rats to see whether OB glomerular astrocytes are
      involved in the metabolic sensing and adaptation of the olfactory system.
      Glomerular astroglial spreading was much greater in all OB regions of rats fasted
      for 17 hr than in controls. Intra-peritoneal administration of the anorexigenic
      peptide PYY3-36 or glucose in 17 hr-fasted rats respectively decreased their food
      intake or restored their glycemia, and reversed the fasting-induced astroglial
      spreading. Direct application of the orexigenic peptides ghrelin or NPY to OB
      slices increased astroglial spreading, whereas PYY3-36 resulted in astroglial
      retraction, in agreement with the in vivo effects of fasting and satiety on
      glomerular astrocytes. Thus the morphological plasticity of OB glomerular
      astrocytes depends on the metabolic state of the rats and is influenced by
      peptides that regulate food intake. This plasticity may be part of the mechanism
      by which the olfactory system adapts to food intake.

PMID- 29226550
TI  - Alpha-Klotho Enrichment in Induced Pluripotent Stem Cell Secretome Contributes to
      Antioxidative Protection in Acute Lung Injury.
AB  - Induced pluripotent stem cells (iPSCs) have been reported to alleviate organ
      injury, although the mechanisms of action remain unclear and administration of
      intact cells faces many limitations. We hypothesized that cell-free conditioned
      media (CM) containing the secretome of iPSCs possess antioxidative constituents
      that can alleviate pulmonary oxidant stress damage. We derived iPSCs from human
      dermal fibroblasts and harvested the CM. Addition of iPSC CM to cultured human
      alveolar type-1 epithelial cells mitigated hyperoxia-induced depletion of
      endogenous total antioxidant capacity while tracheal instillation of iPSC CM into
      adult rat lungs enhanced hyperoxia-induced increase in TAC. In both the in vitro
      and in vivo models, iPSC CM ameliorated oxidative damage to DNA, lipid, and
      protein, and activated the nuclear factor (erythroid 2)-related factor 2 (Nrf2)
      network of endogenous antioxidant proteins. Compared with control fibroblast
      conditioned or cell-free media, iPSC CM is highly enriched with alphaKlotho at a
      concentration up to more than 10-fold of that in normal serum. alphaKlotho is an
      essential antioxidative cell maintenance and protective factor and an activator
      of the Nrf2 network. Immunodepletion of alphaKlotho reduced iPSC CM-mediated
      cytoprotection by ~50%. Thus, the abundant alphaKlotho content significantly
      contributes to iPSC-mediated antioxidation and cytoprotection. Results uncover a
      major mechanism of iPSC action, suggest a fundamental role of alphaKlotho in iPSC
      maintenance, and support the translational potential of airway delivery of cell
      free iPSC secretome for protection against lung injury. The targeted cell-free
      secretome-based approach may also be applicable to the amelioration of injury in
      other organs. Stem Cells 2018;36:616-625.

PMID- 29226551
TI  - Premenstrual symptoms interference and equol production status in Japanese
      collegiate athletes: A cross-sectional study.
AB  - AIM: Consumption of soy isoflavones reduces the risk of estrogen-related
      diseases, such as menopausal symptoms, osteoporosis, and cardiovascular disease.
      Equol is metabolized from the isoflavone daidzein by intestinal bacteria and has
      higher bioavailability than other isoflavones. Equol producers are believed to
      benefit from soybean consumption to a greater extent than non-producers.
      Recently, we showed that equol non-producers were at significant risk of
      premenstrual syndrome (PMS). Previously, we reported that PMS is a common
      menstrual problem in female athletes, and almost half of the studied athletes
      felt a negative effect of premenstrual symptoms on their athletic performance.
      This study was conducted to evaluate the relation between PMS and equol
      production status in Japanese collegiate athletes. METHODS: This was a cross
      sectional, observational study that included 88 Japanese female collegiate
      athletes. Equol production status was determined using urine samples collected
      after a soy challenge test. The subjects also completed a questionnaire about
      their premenstrual symptoms and their competitive career. RESULTS: The prevalence
      of equol producers was 29.5% in Japanese collegiate athletes. The athletic
      performance of 54.5% of athletes was found to suffer in competition or in
      practice due to premenstrual symptoms. In multivariate analysis, equol non
      producers (odds ratio, 3.34; 95% confidence interval, 1.03-12.20) and restriction
      of bodyweight (odds ratio, 4.94; 95% confidence interval, 1.47-20.00) were shown
      to be significant risk factors for poor athletic performance. CONCLUSION: This
      study showed a relation between athletic performance and equol production status
      in Japanese collegiate athletes.

PMID- 29226552
TI  - Spontaneously regressing brain lesions in Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn
      error of cholesterol synthesis that affects the development of many organ
      systems. Malformations in the central nervous system typically involve midline
      structures and reflect abnormal growth and differentiation of neurons and
      supporting cells. Despite these defects in central nervous system development,
      brain tumor formation has only rarely been reported in association with SLOS. We
      present three individuals with SLOS and lesions in the basal ganglia or brainstem
      detected by MRI that were concerning for tumor formation. However, the
      individuals' clinical and neurological course remained stable, and the lesions
      regressed after several years. These lesions have similarities to spongiotic
      changes observed in individuals with neurofibromatosis type 1 (NF1). Notably,
      impaired activity of small GTPases is present in both SLOS and NF1, perhaps
      giving mechanistic insight into the formation of these lesions.

PMID- 29226553
TI  - Design and properties of a novel radiopaque injectable apatitic calcium phosphate
      cement, suitable for image-guided implantation.
AB  - An injectable purely apatitic calcium phosphate cement (CPC) was successfully
      combined to a water-soluble radiopaque agent (i.e., Xenetix(r) ), to result in an
      optimized composition that was found to be as satisfactory as poly(methyl
      methacrylate) (PMMA) formulations used for vertebroplasty, in terms of
      radiopacity, texture and injectability. For that purpose, the Xenetix dosage in
      the cement paste was optimized by injection of the radiopaque CPC in human
      cadaveric vertebrae under classical PMMA vertebroplasty conditions, performed by
      interventional radiologists familiar with this surgical procedure. When present
      in the cement paste up to 70 mg I mL-1 , Xenetix did not influence the
      injectability, cohesion, and setting time of the resulting composite. After
      hardening of the material, the same observation was made regarding the
      microstructure, mechanical strength and alpha-tricalcium phosphate to calcium
      deficient apatite transformation rate. Upon implantation in bone in a small
      animal model (rat), the biocompatibility of the Xenetix-containing CPC was
      evidenced. Moreover, an almost quantitative release of the contrast agent was
      found to occur rapidly, on the basis of in vitro static and dynamic quantitative
      studies simulating in vivo implantation. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 2786-2795, 2018.

PMID- 29226554
TI  - Controllable Solid Electrolyte Interphase in Nickel-Rich Cathodes by an
      Electrochemical Rearrangement for Stable Lithium-Ion Batteries.
AB  - The layered nickel-rich materials have attracted extensive attention as a
      promising cathode candidate for high-energy density lithium-ion batteries (LIBs).
      However, they have been suffering from inherent structural and electrochemical
      degradation including severe capacity loss at high electrode loading density
      (>3.0 g cm-3 ) and high temperature cycling (>60  degrees C). In this study, an
      effective and viable way of creating an artificial solid-electrolyte interphase
      (SEI) layer on the cathode surface by a simple, one-step approach is reported. It
      is found that the initial artificial SEI compounds on the cathode surface can
      electrochemically grow along grain boundaries by reacting with the by-products
      during battery cycling. The developed nickel-rich cathode demonstrates
      exceptional capacity retention and structural integrity under industrial
      electrode fabricating conditions with the electrode loading level of ~12 mg cm-2
      and density of ~3.3 g cm-3 . This finding could be a breakthrough for the LIB
      technology, providing a rational approach for the development of advanced cathode
      materials.

PMID- 29226555
TI  - Climate warming is associated with smaller body size and shorter lifespans in
      moose near their southern range limit.
AB  - Despite the importance of body size for individual fitness, population dynamics
      and community dynamics, the influence of climate change on growth and body size
      is inadequately understood, particularly for long-lived vertebrates. Although
      temporal trends in body size have been documented, it remains unclear whether
      these changes represent the adverse impact of climate change (environmental
      stress constraining phenotypes) or its mitigation (via phenotypic plasticity or
      evolution). Concerns have also been raised about whether climate change is indeed
      the causal agent of these phenotypic shifts, given the length of time-series
      analysed and that studies often do not evaluate - and thereby sufficiently rule
      out - other potential causes. Here, we evaluate evidence for climate-related
      changes in adult body size (indexed by skull size) over a 4-decade period for a
      population of moose (Alces alces) near the southern limit of their range whilst
      also considering changes in density, predation, and human activities. In
      particular, we document: (i) a trend of increasing winter temperatures and
      concurrent decline in skull size (decline of 19% for males and 13% for females)
      and (ii) evidence of a negative relationship between skull size and winter
      temperatures during the first year of life. These patterns could be plausibly
      interpreted as an adaptive phenotypic response to climate warming given that
      latitudinal/temperature clines are often accepted as evidence of adaptation to
      local climate. However, we also observed: (iii) that moose with smaller skulls
      had shorter lifespans, (iv) a reduction in lifespan over the 4-decade study
      period, and (v) a negative relationship between lifespan and winter temperatures
      during the first year of life. Those observations indicate that this phenotypic
      change is not an adaptive response to climate change. However, this decline in
      lifespan was not accompanied by an obvious change in population dynamics,
      suggesting that climate change may affect population dynamics and life-histories
      differently.

PMID- 29226556
TI  - Solvent or thermal extraction of ethylene oxide from polymeric materials: Medical
      device considerations.
AB  - Ethylene oxide (EO) gas is commonly used to sterilize medical devices.
      Bioavailable residual EO, however, presents a significant toxicity risk to
      patients. Residual EO is assessed using international standards describing
      extraction conditions for different medical device applications. We examine a
      series of polymers and explore different extraction conditions to determine
      residual EO. Materials were sterilized with EO and exhaustively extracted in
      water, in one of three organic solvents, or in air using thermal desorption. The
      EO exhaustively extracted varies significantly and is dictated by two factors:
      the EO that permeates the material during sterilization; and the effectiveness of
      the extraction protocol in flushing residual EO from the material. Extracted EO
      is maximized by a close matches between Hildebrand solubility parameters
      deltapolymer , deltaEO , and deltasolvent . There remain complexities to resolve,
      however, because maximized EO uptake and detection are accompanied by great
      variability. These observations may inform protocols for material selection,
      sterilization, and EO extraction. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
      Res Part B: Appl Biomater, 106B: 2455-2463, 2018.

PMID- 29226557
TI  - Lysophosphatidic acid accelerates development of porcine embryos by activating
      formation of the blastocoel.
AB  - Culture media modifications, including the addition of various factors, are
      important for the in vitro production of oocytes and embryos. In this study, we
      investigated the effects of lysophosphatidic acid (LPA) on porcine embryo
      development. Porcine parthenogenetic embryos were cultured with 0, 0.1, 1, and 10
      MUM LPA for 7 days, or cultured in basic medium until Day 4 and then treated with
      LPA from Days 4 to 7. No difference in the in vitro development of embryos
      cultured with LPA for 7 days was observed. Conversely, rates of blastocyst and
      over-expanded blastocyst formation were higher in the 0.1 and 1 uM LPA-treated
      versus the other groups of embryos treated from Days 4 to 7. Moreover, formation
      of early blastocysts occurred earlier and embryo size was larger in LPA-treated
      compared to control embryos. Expression of Connexin 43 and gap junction and cell
      adhesion-related genes (GJC1 and CDH1, respectively) was also higher in LPA
      treated compared to control embryos. Despite no difference in the blastocyst
      total cell number between groups, the apoptotic index was lower in the LPA
      treated group than in the control group; indeed, BCL2L1 (B-cell lymphoma 2-like
      protein 1) expression increased while BAK (Bcl-2 homologous antagonist killer)
      decreased in the LPA-treated group. Thus, addition of LPA to the medium from Days
      4 to 7 of culture improves blastocyst formation and aids the development of
      preimplantation embryos.

PMID- 29226558
TI  - Detection of the Human Anti-ActRII Antibody Bimagrumab in Serum by Means of
      Affinity Purification, Tryptic Digestion, and LC-HRMS.
AB  - PURPOSE: Inhibitors of the ActRII signaling pathways represent promising
      therapeutics for the treatment of muscular diseases, but also pose risks as
      performance-enhancing agents in sports. Bimagrumab is a human anti-ActRII
      antibody which was found to increase muscle mass and function by blocking ActRII
      signaling. As it has considerable potential for being misused as doping agent in
      sports, the aim of this study was to develop a mass spectrometric detection assay
      for doping control serum samples. EXPERIMENTAL DESIGN: Within this study, a
      detection method for Bimagrumab in human serum was developed, which combines
      ammonium sulfate precipitation and affinity purification with proteolytic
      digestion and LC-HRMS. To facilitate the unambiguous identification of the
      diagnostic peptides, an orthogonal IM separation was additionally performed.
      RESULTS: The assay was successfully validated and the analysis of clinical
      samples demonstrated its fitness for purpose for an application in routine doping
      control analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Although no myostatin
      inhibitors have obtained clinical approval yet, the proactive development of
      detection methods for emerging doping agents represents a key aspect of
      preventive doping research. The presented approach will expand the range of
      available tests for novel protein therapeutics and can readily be modified to
      include further target analytes.

PMID- 29226559
TI  - Nature's genetic screens: using genome-wide association studies for effector
      discovery.

PMID- 29226560
TI  - A Highly Efficient Oxygen Evolution Catalyst Consisting of Interconnected Nickel
      Iron-Layered Double Hydroxide and Carbon Nanodomains.
AB  - In this work, a one-pot solution method for direct synthesis of interconnected
      ultrafine amorphous NiFe-layered double hydroxide (NiFe-LDH) (<5 nm) and
      nanocarbon using the molecular precursor of metal and carbon sources is presented
      for the first time. During the solvothermal synthesis of NiFe-LDH, the organic
      ligand decomposes and transforms to amorphous carbon with graphitic nanodomains
      by catalytic effect of Fe. The confined growth of both NiFe-LDH and carbon in one
      single sheet results in fully integrated amorphous NiFe-LDH/C nanohybrid,
      allowing the harness of the high intrinsic activity of NiFe-LDH due to (i)
      amorphous and distorted LDH structure, (ii) enhanced active surface area, and
      (iii) strong coupling between the active phase and carbon. As such, the resultant
      NiFe-LDH/C exhibits superior activity and stability. Different from
      postdeposition or electrostatic self-assembly process for the formation of LDH/C
      composite, this method offers one new opportunity to fabricate high-performance
      oxygen evolution reaction and possibly other catalysts.

PMID- 29226561
TI  - The long-term effects of faecal microbiota transplantation for gastrointestinal
      symptoms and general health in patients with recurrent Clostridium difficile
      infection.
AB  - BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for
      recurrent Clostridium difficile infection. In short-term the treatment has been
      shown to be safe, however, there are no large, long-term follow-up studies
      looking into the potential adverse effects. AIM: To analyse the long-term effect
      of FMT treatment in patients with recurrent C. difficile infection and to compare
      the outcome to antibiotic treated patients. METHODS: Altogether 84 patients of
      which 45 received a FMT treatment and 39 served as controls receiving antibiotics
      for the infection were followed on average for 3.8 years. Their recovery and
      medical status was evaluated using a retrospective questionnaire, determining
      their quality of life, gastrointestinal symptoms and new diseases potentially
      related to the FMT. RESULTS: There was no difference in the incidence of severe
      diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy,
      neurological diseases) between the patient groups. In addition, weight gain did
      not differ between treatment groups. The FMT treated patients reported that their
      bowel habits improved significantly faster, they had less irregular bowel
      function and less symptoms of upper GI-tract when compared to the patients
      treated with antibiotics. Significantly more patients in FMT-group reported that
      their mental health improved after the treatment. The willingness to receive FMT
      treatment for potential new C. difficile infection was significantly higher in
      both treatment groups compared to other treatment options. CONCLUSION: Our study
      highlights that FMT is a durable, safe and acceptable treatment option for
      patients with recurrent C. difficile infection also in long term, and it shows
      potential benefits over antimicrobial treatment.

PMID- 29226562
TI  - Enantio- and Diastereoselective Cyclopropanation of 1-Alkenylboronates: Synthesis
      of 1-Boryl-2,3-Disubstituted Cyclopropanes.
AB  - A novel, highly enantio- and diastereoselective synthesis of 1-boryl-2,3
      disubstituted cyclopropanes has been developed by means of the cyclopropanation
      of alkenylboronates with ethyl diazoacetate in the presence of catalytic amounts
      of a chiral copper(I) complex. The products can also be directly accessed from
      alkynes through an operationally simple, sequential hydroboration
      cyclopropanation protocol. The resulting enantioenriched 1-boryl-2,3
      disubstituted cyclopropanes are versatile synthetic intermediates that undergo
      further transformations at the carbon-boron bond.

PMID- 29226563
TI  - Fatal cardiac arrest in pediatric heart transplant recipients: Query of the UNOS
      database.
AB  - The incidence of death by CA after PHTx is unknown. We aimed to determine the
      incidence and factors for fatal CA after PHTx, and whether a PM affects survival.
      Retrospective cohort study utilizing the United Network of Organ Sharing registry
      of patients transplanted <=18 years. Multivariable analyses in hazard-function
      domain and Kaplan-Meier analyses were performed for an outcome of death due to
      CA. There were 7719 PHTx patients queried. CA was the reported cause of death in
      11%. Age >=13 years at time of transplant, presence of a PM, and depressed EF
      were identified as significant factors for fatal CA. Death due to CA beyond 10
      years post-transplant was associated with depressed EF, CAV, and presence of a
      PM. Kaplan-Meier analysis demonstrated higher likelihood of fatal CA in patients
      with CAV and in those with a PM vs those without. In total, 15% of patients with
      a PM died from CA. CA is a relatively common cause of death after PHTx. The
      benefit of a PM remains unclear, but its presence does not confer complete
      protection. Patients with associated factors warrant vigilant surveillance and
      consideration for retransplantation.

PMID- 29226565
TI  - Authors' reply re: Starting a Uterus transplantation service: Notes from a small
      island.

PMID- 29226564
TI  - "Lowe syndrome: A particularly severe phenotype without clinical kidney
      involvement".
AB  - Lowe syndrome (LS) is a very rare disorder of phosphatidylinositol metabolism,
      which manifests with a complex phenotype comprising a clinical triad encompassing
      major abnormalities of the eyes, the kidneys, and the central nervous system. We
      are reporting a 23-year-old Egyptian male with a severe phenotype of LS with a
      minimal kidney disease. Direct sequencing of the OCRL gene detected a p.His375Arg
      mutation in the catalytic domain of the protein. The patient suffered from
      bilateral congenital cataracts and glaucoma, striking growth deficiency, severe
      psychomotor disability, a severe osteopathy, and seizures, but only minimal renal
      dysfunction. Although the biological mechanisms underlying the pathophysiology of
      LS manifestations is yet unclear, it has been proposed that growth delay and
      osteopathy are linked to a renal dysfunction. This report, however, argues this
      association and suggests that kidney dysfunction may partially explain the growth
      deficiency and bone abnormalities, but other still undefined factors might have a
      potential impact.

PMID- 29226566
TI  - Probing the importance of clonality: Single cell subcloning of clonally derived
      CHO cell lines yields widely diverse clones differing in growth, productivity,
      and product quality.
AB  - In the past few decades, a large variety of therapeutic antibodies and proteins
      have been expressed in Chinese hamster ovary (CHO) cells. This mammalian
      expression system is robust, scalable, relatively inexpensive, and importantly
      allows for post-translational modifications that are important for some
      therapeutic proteins. Historically, CHO cell lines were derived from colonies of
      cells grown in semi-solid or liquid plates using either serum-containing or serum
      free media. Current advancements in cell sorting and imaging technologies have
      allowed for isolating and imaging single cell progenitors at the seeding step,
      significantly increasing the probability of isolating clonally derived cell
      lines. However, it is debatable how much population heterogeneity can be
      eliminated when clonally derived cell lines, originated from a single cell
      progenitor, are scaled up. To further investigate this phenomenon, we subcloned
      two different clonally derived (day 0 imaged and visually inspected) cell lines
      expressing antibody-X. The results showed that when six randomly chosen subclones
      of each line were evaluated in a production assay, these subclones displayed a
      range of variation in titer, specific productivity, growth, and product quality
      attributes. Some subclones displayed variations in transgene copy numbers.
      Additionally, clonal derivation did not assure stability of the derived cell
      lines. Our findings show that cell heterogeneity exists in a population even when
      derived from a single cell progenitor. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:624-634, 2018.

PMID- 29226567
TI  - A strain-specific multiplex RT-PCR for Australian rabbit haemorrhagic disease
      viruses uncovers a new recombinant virus variant in rabbits and hares.
AB  - Rabbit haemorrhagic disease virus (RHDV, or GI.1) is a calicivirus in the genus
      Lagovirus that has been widely utilized in Australia as a biological control
      agent for the management of overabundant wild European rabbit (Oryctolagus
      cuniculus) populations since 1996. Recently, two exotic incursions of pathogenic
      lagoviruses have been reported in Australia; GI.1a-Aus, previously called RHDVa
      Aus, is a GI.1a virus detected in January 2014, and the novel lagovirus GI.2
      (previously known as RHDV2). Furthermore, an additional GI.1a strain, GI.1a-K5
      (also known as 08Q712), was released nationwide in March 2017 as a supplementary
      tool for wild rabbit management. To discriminate between these lagoviruses, a
      highly sensitive strain-specific multiplex RT-PCR assay was developed, which
      allows fast, cost-effective and sensitive detection of the four pathogenic
      lagoviruses currently known to be circulating in Australia. In addition, we
      developed a universal RT-qPCR assay to be used in conjunction with the multiplex
      assay that broadly detects all four viruses and facilitates quantification of
      viral RNA load in samples. These assays enable rapid detection, identification
      and quantification of pathogenic lagoviruses in the Australian context. Using
      these assays, a novel recombinant lagovirus was detected in rabbit tissue
      samples, which contained the non-structural genes of GI.1a-Aus and the structural
      genes of GI.2. This variant was also recovered from the liver of a European brown
      hare (Lepus europaeus). The impact of this novel recombinant on Australian wild
      lagomorph populations and its competitiveness in relation to circulating field
      strains, particularly GI.2, requires further studies.

PMID- 29226568
TI  - Incidence of contamination of live bird markets in Bangladesh with influenza A
      virus and subtypes H5, H7 and H9.
AB  - In the absence of robust active surveillance of avian influenza viruses (AIV)
      affecting poultry in South Asian countries, monitoring of live bird markets
      (LBMs) can be an alternative. In a longitudinal study of 32 LBM, five
      environments were sampled as follows: market floor, stall floor, slaughter area,
      poultry holding cage and water used for meat processing. Samples were taken
      monthly for 5 months, September 2013-January 2014. Incidence rates (IRs) of LBM
      contamination with AIV and its subtypes H5, H7 and H9 were assessed. In 10 of the
      LBM selected, biosecurity measures had been implemented through FAO
      interventions: the other 22 were non-intervened. Standard procedures were applied
      to detect AIV and three subtypes in pooled samples (1:5). An LBM was considered
      positive for AIV or a subtype if at least one of the pooled samples tested
      positive. The incidence rates of LBM contamination with AIV, H5, H7 and H9 were
      0.194 (95% confidence interval (CI) 0.136-0.276), 0.031 (95% CI 0.013-0.075), 0
      and 0.175 (95% CI 0.12-0.253) per LBM-month at risk, respectively. The log IR
      ratio between the FAO-intervened and non-intervened LBM for contamination with
      AIV was -0.329 (95% CI -1.052 to -0.394, p = .372), 0.598 (95% CI -1.593 to
      2.789, p = .593) with subtype H5 and -0.500 (95% CI -1.249 to 0.248, p = .190)
      with subtype H9, indicating no significant difference. The results obtained
      suggest that both H5 and H9 were circulating in LBM in Bangladesh in the second
      half of 2013. The incidence of contamination with H9 was much higher than with
      H5.

PMID- 29226569
TI  - Children Born by Women With Rheumatoid Arthritis and Increased Susceptibility for
      Chronic Diseases: A Nationwide Cohort Study.
AB  - OBJECTIVE: Fetal exposure to maternal rheumatoid arthritis (RA) might impact the
      long-term risk of disease in the offspring. We examined a possible association
      between maternal RA and 15 selected groups of chronic diseases in the offspring.
      METHODS: This nationwide cohort study was based on the Danish health registries
      and included data on all children born alive in Denmark between January 1, 1989
      and December 31, 2013. The cohort comprised 2,106 children born by women with RA
      (exposed), and 1,378,539 children born by women without RA (unexposed). Cox
      proportional hazards regression models were used, taking a large range of
      confounders into consideration, and the hazard ratios (HRs) of child and
      adolescent diseases were calculated. RESULTS: In children exposed to maternal RA
      in utero, the HR of thyroid diseases was 2.19 (95% confidence interval [95% CI]
      1.14-4.21), epilepsy 1.61 (95% CI 1.16-2.25), and RA 2.89 (95% CI 2.06-4.05). The
      HRs for anxiety and personality disorders and chronic lung disease including
      asthma were in the range of 1.15-1.16, but these were not statistically
      significant associations. CONCLUSION: Our results suggest that in utero exposure
      to maternal RA is associated with an increased risk of thyroid disease and
      epilepsy in childhood and adolescence, and in particular an increased risk of RA,
      compared to children born to mothers without RA. These important findings should
      encourage pediatricians and general practitioners to have an increased awareness
      of certain chronic diseases in children exposed to RA in utero.

PMID- 29226570
TI  - Campath, calcineurin inhibitor reduction, and chronic allograft nephropathy (the
      3C Study) - results of a randomized controlled clinical trial.
AB  - Calcineurin inhibitors (CNIs, eg, tacrolimus) reduce short-term kidney transplant
      failure, but chronic nephrotoxicity may contribute to late transplant loss.
      Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg,
      sirolimus) pathway might avoid long-term CNI renal damage and improve outcomes.
      The 3C Study was a pragmatic randomized controlled trial of sequential
      randomizations between alemtuzumab and basiliximab induction therapy (at the time
      of surgery) and between tacrolimus and sirolimus maintenance therapy at 6 months
      posttransplantation. The primary outcome of this analysis was estimated
      glomerular filtration rate (eGFR) at 18 months after maintenance therapy
      randomization; 197 patients were assigned sirolimus-based and 197 to tacrolimus
      based therapy. Allocation to sirolimus had no significant effect on eGFR at 18
      months: baseline-adjusted mean (SEM) eGFR was 53.7 (0.9) mL/min/1.73 m2 in the
      sirolimus group versus 54.6 (0.9) mL/min/1.73 m2 in the tacrolimus group (P =
      .50). Biopsy-proven acute rejection (29 [14.7%]) vs 6 [3.0%]; P < .001) and
      serious infections (defined as opportunistic infections or those requiring
      hospitalization; 95 [48.2%] vs 70 [35.5%]; P = .008) were more common among
      participants allocated sirolimus. Compared with tacrolimus-based therapy,
      sirolimus-based maintenance therapy did not improve transplant function at 18
      months after conversion and was associated with significant hazards of rejection
      and infection. ClinicalTrials.gov identifier NCT01120028 and ISRCTN88894088.

PMID- 29226571
TI  - Mouse models of psoriasis and their relevance.
AB  - Psoriasis is an inflammatory skin disorder that includes dynamic interactions
      between the immune system and skin and is clinically characterized by
      keratinocyte proliferation and distinct inflammatory cell infiltrates. Cross-talk
      between keratinocytes and immunocytes is essential for the development of
      psoriasis given that it mediates the production of cytokines, chemokines and
      growth factors. To resolve the pathogenesis of psoriasis, numerous experimental
      animal models have been generated. In this review, we discuss recent findings
      from mouse models, their relevancy to psoriasis and use, including the discovery
      of new therapies.

PMID- 29226572
TI  - Nitroglycerin and the enduring principles of coronary procedures.
AB  - The benefits of nitroglycerin are numerous, from ensuring accurate interpretation
      of diagnostic angiograms to treatment of coronary spasm and support of PCIs in
      simple or complex lesion types. The founders of the field were convinced that no
      coronary arteriography should be considered complete unless a vasodilator is used
      at some point during the study. This recommendation is valid. The guidelines
      should change to include administration of intracoronary nitroglycerin.

PMID- 29226574
TI  - Ready, set, pull, ow!
AB  - The BADFORM technique is a novel technique in getting devices across otherwise
      uncrossable lesions It is critical to perform the pulling parallel to the vessel
      The technique and its success has only been described in the 10 cases reported so
      caution is advised.

PMID- 29226573
TI  - Power of gradients.
AB  - Patients with high baseline gradients benefit most after TAVR. In severe
      symptomatic aortic stenosis, every 10 mm Hg increase in mean gradient has 20%
      reduction in mortality after TAVR. Low gradient severe aortic stenosis continues
      to be a clinical cohort with variable benefit from TAVR.

PMID- 29226575
TI  - Vulnerable plaques, more than meets the i.
AB  - Intravascular imaging plays a key role in the identification of mechanisms of
      acute coronary syndromes Post processing IVUS algorithms (IMAP-IVUS and VH-IVUS)
      for tissue characterization have not been widely adopted due to current
      limitations Future development will allow easier, faster, and more accurate
      identification of vulnerable plaques, ultimately allowing prognostication of
      various interventions.

PMID- 29226576
TI  - Deferred lesion failure in diabetes: A truly bad actor.
AB  - DM patients with stenoses whose FFR > 0.80 have a relatively high 14% rate of
      deferred lesion failure (i.e., revascularization or MI). IDDM and prior
      revascularization were independent predictors of deferred lesion failure FFR
      predicts outcomes, but is a less effective predictor in diabetics due to diffuse
      atherosclerosis microvascular disease.

PMID- 29226577
TI  - A cardiologist's nightmare: Coronary obstruction during transcatheter aortic
      valve implantation: How to identify patients at highest risk for this
      complication.
AB  - Transcatheter aortic valve implantation (TAVI) is associated with several
      complications including coronary obstruction (CO) CO occurs in ~1% of patients
      and mostly in patients receiving the SAPIEN XT valve Possible predictors of CO
      include coronary height <10 mm and aortic sinus diameter of <30 mm.

PMID- 29226578
TI  - Ischemia-reperfusion injury and ischemic post-conditioning in acute myocardial
      infarction: Lost in translation.
AB  - Ischemic post-conditioning (IPoC) has been proposed as a strategy to mitigate the
      risk of ischemia-reperfusion injury during primary percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI). In this
      comprehensive and updated meta-analysis of randomized controlled trials, IPoC
      during primary PCI for STEMI had no significant effect on all-cause mortality, re
      infarction, or new-onset heart failure compared with no post-conditioning.
      Further strategies need to be prospectively evaluated to improve outcomes in
      patients with STEMI undergoing primary PCI.

PMID- 29226579
TI  - Sirens song or a bugle call to charge.
AB  - Radial access for catheterization is associated with reduced bleeding and
      mortality across a spectrum of clinical conditions compared to femoral.
      Transradial technique is associated with a higher rate of access site failure but
      this is in those most likely to have a femoral-based complication. Improved
      outcomes will come with further radial technique refinement and not with a
      retreat to legacy femoral approaches.

PMID- 29226580
TI  - A novel truncating variant within exon 7 of KAT6B associated with features of
      both Say-Barber-Bieseker-Young-Simpson syndrome and genitopatellar syndrome:
      Further evidence of a continuum in the clinical spectrum of KAT6B-related
      disorders.
AB  - KAT6B sequence variants have been identified in both patients with the Say-Barber
      Biesecker-Young-Simpson syndrome (SBBYSS) and in the genitopatellar syndrome
      (GPS). In SBBYSS, they were reported to affect mostly exons 16-18 of KAT6B, and
      the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss
      of protein function. Truncating variants in KAT6B leading to GPS appear to
      cluster within the proximal portion of exon 18, associated with a dominant
      negative effect of the mutated protein, most likely. Although SBBYSS and GPS have
      been initially considered allelic disorders with distinctive genetic and clinical
      features, there is evidence that they represent two ends of a spectrum of
      conditions referable as KAT6B-related disorders. We detected a de novo truncating
      variant within exon 7 of KAT6B in a 8-year-old female who presented with mild
      intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and
      skeletal anomalies including exostosis, that are usually considered component
      manifestations of GPS. Following the clinical diagnosis driven by the striking
      facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present
      report highlights the pivotal role of clinical genetics in avoiding clear-cut
      genotype-phenotype categories in syndromic forms of intellectual disability. In
      addition, it further supports the evidence that a continuum exists within the
      clinical spectrum of KAT6B-associated disorders.

PMID- 29226581
TI  - Mixoploidy combined with aneuploidy in a 13 year-old patient with severe multiple
      congenital abnormalities and intellectual disability.

PMID- 29226583
TI  - Reducing the burden of diabetes complications.

PMID- 29226582
TI  - Proof of concept testing of a positive reference material for in vivo and in
      vitro skin irritation testing.
AB  - In vivo and in vitro irritation testing is important for evaluating the
      biological safety of medical devices. Here, the performance of positive reference
      materials for skin irritation testing was evaluated. Four reference standards,
      referred to as Y-series materials, were analyzed: a polyvinyl chloride (PVC)
      sheet spiked with 0 (Y-1), 1.0 (Y-2), 1.5 (Y-3), or 10 (Y-4) parts of Genapol X
      080 per 100 parts of PVC by weight. Y-1, Y-2, and Y-3 did not induce skin
      irritation responses in an in vitro reconstructed human epidermis (RhE) tissue
      model, as measured by tissue viability or interleukin-1alpha release, or in an in
      vivo intracutaneous response test using rabbits. In contrast, Y-4 extracts
      prepared with saline or sesame oil at 37 degrees C and 50 degrees C clearly
      elicited positive irritation responses, including reduced viability (< 50%) and
      significantly higher interleukin-1alpha release compared with the solvent alone
      group, in the RhE tissue model and an intracutaneous response test, where
      substantial necrosis was observed by histopathology. The positive skin irritation
      responses induced in vitro under various extraction conditions, as well as those
      elicited in vivo, indicate that Y-4 is an effective extractable positive control
      material for in vivo and in vitro skin irritation tests of medical devices. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2807
      2814, 2018.

PMID- 29226584
TI  - Wool-derived keratin hydrogel enhances implant osseointegration in cancellous
      bone.
AB  - AIM: This study investigated whether a keratin hydrogel derived from wool
      enhances ossointegration of dental implants, using a cancellous bone model in
      sheep. METHOD: Ten female sheep received one dental implant per hind leg in the
      distal femoral condyles. Test implants were coated with 1 mL of keratin hydrogel
      containing sulphonated keratin and hydroxyapatite; control implants remained
      uncoated; implants were not functionally loaded axially. Biomechanical stability
      was tested with resonance frequency analysis (RFA) at placement and euthanasia.
      Animals were sacrificed after 4 weeks and resin-embedded histomorphometry
      performed. FINDINGS: Bone appeared denser and more mature around the keratin
      treated test implants. Average % bone-implant contact was significantly increased
      for the test (58.1 +/- 4.6 [SD]%) compared to control implants (34.4 +/- 7.5%) (p
      = 0.01). RFA values were lower for control (76.5 +/- 4.2 ISQ) than test implants
      (80.4 +/- 1.4) after 4 weeks (p = 0.04). CONCLUSION: the increase in
      osseointegration found in this model suggests that keratin hydrogel has the
      potential to enhance the successful osseointegration of dental implants placed
      into poor quality bone. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 2447-2454, 2018.

PMID- 29226585
TI  - Block Copolymer Self-Assembly in Solution-Quo Vadis?
AB  - The desire to increase complexity while maintaining control over every aspect of
      the process itself might be used as a provocative description of the developments
      in block copolymer self-assembly in solution over the last decade. The community
      has witnessed tremendous progress, not only with regard to the design of building
      blocks, but also in terms of understanding assembly pathways, interfacial
      properties, or kinetic obstacles. In particular, the latter can be of interest
      (and actually turned into an advantage) if structures that are not in
      thermodynamic equilibrium are targeted. Within this focus review, we aim to
      highlight the key developments and trends that we have identified during the last
      five years: the development of step-wise and dynamic processes, different means
      to impart further hierarchy into solution-borne nanostructures, and a partial
      shift in focus towards gradient and bottlebrush block copolymers.

PMID- 29226586
TI  - Protective effect of gentiopicroside from Gentiana macrophylla Pall. in ethanol
      induced gastric mucosal injury in mice.
AB  - Gentiopicroside isolated from gentiana macrophylla Pall. belongs to iridoid
      glycosides. This study aimed to evaluate the protective effect of gentiopicroside
      against ethanol-induced gastric mucosal injury in mice. Mice were proactively
      administrated with gentiopicroside by intragastric administration once a day for
      3 consecutive days. On the 3rd day, gastric ulcer in mice was induced with 70%
      ethanol after the last intragastric administration. The stomach tissues were
      submitted for evaluation of the severity of gastric mucosal alterations.
      Gentiopicroside administrated orally ameliorated the severity of gastric mucosal
      alterations. Oral administration of gentiopicroside significantly increased heat
      shock protein-70 and glutathione levels and superoxide dismutase activity,
      normalized epidermal growth factor and vascular endothelial growth factor levels,
      and decreased the levels of tumour necrosis factor-alpha, interleukin-6 and
      malondialdehyde, and myeloperoxidase activity in gastric tissue. These findings
      demonstrated that gentiopicroside has protective effect against ethanol-induced
      gastric mucosal injury in mice through the improvements of antioxidative and anti
      inflammatory effects, as well as up-regulation of heat shock protein-70 level and
      normalization of epidermal growth factor and vascular endothelial growth factor
      levels. The results presented in this study provide some evidence for the
      development of a novel antigastric ulcer agent.

PMID- 29226587
TI  - Cellular models for beta-cell function and diabetes gene therapy.
AB  - Diabetes is characterized by the destruction and/or relative dysfunction of
      insulin-secreting beta-cells in the pancreatic islets of Langerhans.
      Consequently, considerable effort has been made to understand the physiological
      processes governing insulin production and secretion in these cells and to
      elucidate the mechanisms involved in their deterioration in the pathogenesis of
      diabetes. To date, considerable research has exploited clonal beta-cell lines
      derived from rodent insulinomas. Such cell lines have proven to be a great asset
      in diabetes research, in vitro drug testing, and studies of beta-cell physiology
      and provide a sustainable, and in many cases, more practical alternative to the
      use of animals or primary tissue. However, selection of the most appropriate
      rodent beta cell line is often challenging and no single cell line entirely
      recapitulates the properties of human beta-cells. The generation of stable human
      beta-cell lines would provide a much more suitable model for studies of human
      beta-cell physiology and pathology and could potentially be used as a readily
      available source of implantable insulin-releasing tissue for cell-based therapies
      of diabetes. In this review, we discuss the history, development, functional
      characteristics and use of available clonal rodent beta-cell lines, as well as
      reflecting on recent advances in the generation of human-derived beta-cell lines,
      their use in research studies and their potential for cell therapy of diabetes.

PMID- 29226588
TI  - Multigene editing via CRISPR/Cas9 guided by a single-sgRNA seed in Arabidopsis.
AB  - We report that a solo single-guide RNA (sgRNA) seed is capable of guiding
      Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR 
      associated 9 (CRISRP/Cas9) to simultaneously edit multiple genes AtRPL10A,
      AtRPL10B and AtRPL10C in Arabidopsis. Our results also demonstrate that it is
      possible to use CRISPR/Cas9 technology to create AtRPL10 triple mutants which
      otherwise cannot be generated by conventional genetic crossing. Compared to other
      conventional multiplex CRISPR/Cas systems, a single sgRNA seed has the advantage
      of reducing off-target gene-editing. Such a gene editing system might be also
      applicable to modify other homologous genes, or even less-homologous sequences
      for multiple gene-editing in plants and other organisms.

PMID- 29226589
TI  - Hydrochlorothiazide and acute urinary acidification: The "voltage hypothesis" of
      ENaC-dependent H+ secretion refuted.
AB  - AIM: The "voltage hypothesis" of H+ secretion states that urinary acidification
      following increased Na+ delivery to the collecting duct (CD) is ENaC dependent
      leading to transepithelial voltage-dependent increase in H+ secretion. We
      recently showed that furosemide acidifies the urine independently of ENaC
      activity. If the voltage hypothesis holds, hydrochlorothiazide (HCT) must acidify
      the urine. We here tested the acute effect of HCT on urine pH under normal and
      high ENaC expression. METHODS: Mice subjected to a control or a low-Na+ diet were
      anesthetized and infused (0.5 mL h-1 ) with saline. Catheterization of the
      urinary bladder allowed real-time measurement of diuresis and urine pH. Mice
      received either HCT (1 mg mL-1 ) or vehicle. Urinary Na+ and K+ excretions were
      determined by flame photometry. ENaC expression levels were measured by semi
      quantitative Western blotting. RESULTS: (1) HCT increased diuresis and
      natriuresis in both diet groups. (2) K+ excretion rates increased after HCT
      administration from 18.6 +/- 1.3 to 31.7 +/- 2.5 MUmol h-1 in the control diet
      group and from 23.0 +/- 1.3 to 48.7 +/- 3.0 MUmol h-1 in the low-Na+ diet group.
      (3) Mice fed a low-Na+ diet showed a marked upregulation of ENaC. (4)
      Importantly, no acute changes in urine pH were observed after the administration
      of HCT in either group. CONCLUSION: Acute administration of HCT has no effect on
      urine pH. Similarly, substantial functional and molecular upregulation of ENaC
      did not cause HCT to acutely change urine pH. Thus, an increased Na+ load to the
      CD does not alter urine pH. This supports our previous finding and likely
      falsifies the voltage hypothesis of H+ secretion.

PMID- 29226590
TI  - DHEAS patterning across childhood in three sub-Saharan populations: Associations
      with age, sex, ethnicity, and cortisol.
AB  - OBJECTIVES: Hormones have many roles in human ontogeny, including the timing of
      life history 'switch points' across development. Limited hormonal data exist from
      non-Western children, leaving a significant gap in our understanding of the
      diversity of life history patterning. This cross-sectional study examines
      dehydroepiandrosterone sulfate (DHEAS) production in relation to age, sex,
      ethnicity, and cortisol concentrations, as well as average age of adrenarche,
      among Aka and Ngandu children of the Central African Republic and Sidama children
      of Ethiopia. METHODS: Hair was collected from 480 children (160 per population)
      aged 3-18 years old. These samples were analyzed for DHEAS and cortisol
      concentrations using ELISAs. A generalized additive model was used to examine
      DHEAS patterning in relation to age, sex, cortisol, and ethnicity. The derivative
      of DHEAS as a function of age was used to identify average age of adrenarche in
      each population. RESULTS: DHEAS patterning in these three populations is distinct
      from Euro-American patterns of production. In all three groups, the population
      level age at adrenarche onset occurs slightly later than Euro-American averages,
      with both Central African populations experiencing a later onset than the
      Ethiopian population. CONCLUSIONS: DHEAS patterns and age at adrenarche vary
      across cultures, perhaps indicating adaptive life history responses in diverse
      eco-cultural environments. Delayed involution of the fetal zone and DHEAS
      patterning may offer both cognitive protection and immune defense in high-risk,
      nutritionally-poor environments. Additional research in the majority world is
      essential to improving our understanding of the diversity of hormonal development
      and timing of 'switch points' in life history trajectories.

PMID- 29226592
TI  - Comment on Hopwood et al., "the time has come for dimensional personality
      disorder diagnosis".

PMID- 29226591
TI  - Validating a prediction modeling tool for left ventricular outflow tract (LVOT)
      obstruction after transcatheter mitral valve replacement (TMVR).
AB  - OBJECTIVE: Demonstrate proof-of-concept validation of a computed tomography (CT)
      computer-aided design prediction modeling tool to identify patients at risk for
      left ventricular outflow tract (LVOT) obstruction in transcatheter mitral valve
      replacement (TMVR). BACKGROUND: LVOT obstruction is a significant and even fatal
      consequence of TMVR. METHODS: From August 2013 to August 2017, 38 patients in 5
      centers underwent TMVR with compassionate use of balloon-expandable valves for
      severe mitral valve dysfunction because of degenerative surgical mitral ring,
      bioprosthesis, or severe native mitral stenosis from to severe mitral annular
      calcification. All patients had preprocedural CT scans performed for anatomic
      screening, intraprocedural TEE and invasive hemodynamics performed. Preprocedural
      prediction modeling was performed utilizing computer-aided design (CAD) of the
      neo-LVOT post-TMVR. Post-TMVR CT scans were obtained and compared to pre-TMVR
      LVOT modeling datasets for validation. RESULTS: All patients underwent successful
      TMVR without device embolization. Seven of the 38 patients experienced LVOT
      obstruction, defined as an increase of >=10 mmHg LVOT peak gradient post-TMVR.
      Anatomic screening using CT was validated in 20/38 patients as preprocedural
      predicted neo-LVOT surface area correlated well with post-TMVR measurements (R2 
      = 0.8169, P < 0.0001). A receiver operating curve curve found a predicted neo
      LVOT surface area of <= 189.4 mm2 to have 100% sensitivity and 96.8% specificity
      for predicting TMVR-induced LVOT obstruction. CONCLUSION: CAD design and CT
      postprocessing are indispensable tools in predicting LVOT obstruction and
      necessary for anatomic screening in percutaneous TMVR.

PMID- 29226593
TI  - The face in marfan syndrome: A 3D quantitative approach for a better definition
      of dysmorphic features.
AB  - Marfan syndrome (MFS) is a rare hereditable disorder of connective tissue caused
      by mutations in the fibrillin-1 gene FBN1. Timely diagnosis of MFS is essential
      to prevent life-threatening cardiovascular complications; nevertheless it can be
      difficult owing to the phenotypic variability of the syndrome. No clear
      quantitative definition of facial abnormalities associated with MFS is available.
      The aim of this study was to improve the definition of the facial phenotype
      associated with MFS and to verify the usefulness of a 3D noninvasive quantitative
      approach for its early recognition. 3D facial images of 61 Italian subjects with
      MFS, aged 16-64 years (21 males, 38 +/- 15 years; 40 females, 41 +/- 13 years)
      were obtained by stereophotogrammetry. From the coordinates of 17 soft-tissue
      facial landmarks, linear distances and angles were computed; z score values were
      calculated to compare patients with healthy reference subjects (400 males, 379
      females) matched for sex and age. Student's t test was used for statistical
      comparisons. All subjects with MFS showed greater facial divergence (P < 0.001;
      mean z score +1.9) and a lower facial height index (P < 0.001; mean z score -1.9)
      than reference subjects, both values being influenced by a shorter mandibular
      ramus (P < 0.001; mean z score -1.9) and a mild but significant increase in
      facial height (P < 0.001; mean z score +1.2). Palpebral down-slanting was found
      in 85% of MFS subjects. There were no sex differences. Quantitative abnormalities
      identified in this study enrich information about the facial dysmorphism in MFS
      and confirm its usefulness for early recognition of the disease. Clin. Anat.
      31:380-386, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29226594
TI  - Selective Surface Enhanced Raman Scattering for Quantitative Detection of Lung
      Cancer Biomarkers in Superparticle@MOF Structure.
AB  - Surface enhanced Raman scattering (SERS) is a trace detection technique that
      extends even to single molecule detection. Its potential application to the
      noninvasive recognition of lung malignancies by detecting volatile organic
      compounds (VOCs) that serve as biomarkers would be a breakthrough in early cancer
      diagnostics. This application, however, is currently limited by two main factors:
      (1) most VOC biomarkers exhibit only weak Raman scattering; and (2) the high
      mobility of gaseous molecules results in a low adsorptivity on solid substrates.
      To enhance the adsorption of gaseous molecules, a ZIF-8 layer is coated onto a
      self-assembly of gold superparticles (GSPs) in order to slow the flow rate of
      gaseous biomarkers and depress the exponential decay of the electromagnetic field
      around the GSP surfaces. Gaseous aldehydes that are released as a result of tumor
      specific tissue composition and metabolism, thereby acting as indicators of lung
      cancer, are guided onto SERS-active GSPs substrates through a ZIF-8 channel.
      Through a Schiff base reaction with 4-aminothiophenol pregrafted onto gold GSPs,
      gaseous aldehydes are captured with a 10 ppb limit of detection, demonstrating
      tremendous prospects for in vitro diagnoses of early stage lung cancer.

PMID- 29226595
TI  - Self-Assembly of TbPc2 Single-Molecule Magnets on Surface through Multiple
      Hydrogen Bonding.
AB  - The complexation between 2-ureido-4[1H]-pyrimidinone (UPy) and 2,7-diamido-1,8
      naphthyridine (NaPy) is used to promote the mild chemisorption of a UPy
      functionalized terbium(III) double decker system on a silicon surface. The
      adopted strategy allows the single-molecule magnet behavior of the system to be
      maintained unaltered on the surface.

PMID- 29226596
TI  - State of the art review: Chemotherapy-induced cardiotoxicity in children.
AB  - Chemotherapy-induced cardiotoxicity in adults and children is a topic with a
      growing interest in the cardiology literature. The ability to detect cardiac
      dysfunction in a timely manner is essential in order to begin adequate treatment
      and prevent further deterioration. This article aims to provide a review on the
      myocardial injury process, chemotherapeutic agents that lead to cardiotoxicity,
      the definition of cardiotoxicity, and the methods of timely detection and
      treatment.

PMID- 29226597
TI  - Prognostic significance of interim 18 F-fluorodeoxyglucose positron emission
      tomography-computed tomography volumetric parameters in metastatic or recurrent
      gastric cancer.
AB  - AIM: To evaluate the prognostic role of interim analysis of 18F
      fluorodeoxyglucose (FDG) positron emission tomography-computed tomography
      (PET/CT) volumetric parameters in patients with recurrent or metastatic advanced
      gastric cancer (AGC) treated with fluoropyrimidine-based palliative chemotherapy.
      METHODS: Forty-four patients who underwent baseline and interim PET/CT scanning
      during palliative chemotherapy were analyzed retrospectively. Initial and change
      of metabolic parameters (MP) - metabolic tumor volume (MTV), tumor lesion
      glycolysis (TLG) and maximum and mean standardized uptake values (SUV) were
      measured with PET/CT. Metabolic change was measured by ?MP (%)  =  (MPinterim  -
      MPinitial )/MP initial   *  100. Independent t-test was employed to compare
      values of initial, interim and change of metabolic parameters between each
      response group. Log-rank test was employed for univariate analysis, and
      multivariate analysis was performed using the Cox proportional hazards regression
      model to determine independently significant prognostic factors. RESULTS: Reduced
      percentage values of maximum and mean SUV on interim PET/CT and initial values of
      volumetric parameters (MTV and TLG) were significant predicting factors to
      response to fluoropyrimidine-based palliative chemotherapy. The decreased
      percentage values of metabolic parameters as well as maximum and mean SUV with
      receiver operating characteristic (ROC) curve determined cut-off points were
      significant prognostic factors for overall survival and progression-free survival
      in univariate and multivariate analyses. CONCLUSION: Measurement of metabolic
      decrease of volumetric parameters by interim PET/CT analysis is useful to
      determine the prognosis of patients with recurrent or metastatic AGC.

PMID- 29226598
TI  - The time has come for dimensional personality disorder diagnosis.

PMID- 29226599
TI  - MicroRNA-transcription factor interactions and their combined effect on target
      gene expression in colon cancer cases.
AB  - Transcription factors (TFs) and microRNAs (miRNAs) regulate gene expression: TFs
      by influencing messenger RNA (mRNA) transcription and miRNAs by influencing mRNA
      translation and transcript degradation. Additionally, miRNAs and TFs alter each
      other's expression, making it difficult to ascertain the effect either one has on
      target gene (TG) expression. In this investigation, we use a two-way interaction
      model with the TF and miRNA as independent variables to investigate whether
      miRNAs and TFs work together to influence TG expression levels in colon cancer
      subjects. We used known TF binding sites and validated miRNA targets to determine
      potential miRNA-TF-TG interactions, restricting interactions to those with a TF
      previously associated with altered risk of colorectal cancer death. We analyzed
      interactions using normal colonic mucosa expression as well as differential
      expression, which is measured as colonic carcinoma expression minus normal
      colonic mucosa expression. We analyzed 3518 miRNA-TF-TG triplets using normal
      mucosa expression and 617 triplets using differential expression. Normal colonic
      RNA-Seq data were available for 168 individuals; of these, 159 also had carcinoma
      RNA-Seq data. Thirteen unique miRNA-TF-TG interactions, comprising six miRNAs,
      four TFs, and 11 TGs, were statistically significant after adjustment for
      multiple comparisons in normal colonic mucosa, and 14 unique miRNA-TF-TG
      interactions, comprising two miRNAs, two TFs, and 13 TGs, were found for
      carcinoma-normal differential expression. Our results show that TG expression is
      influenced by both miRNAs as well as TFs, and the influence of one regulator
      impacts the effect of the other on the shared TG expression.

PMID- 29226601
TI  - A Theoretical Review on Interfacial Thermal Transport at the Nanoscale.
AB  - With the development of energy science and electronic technology, interfacial
      thermal transport has become a key issue for nanoelectronics, nanocomposites,
      energy transmission, and conservation, etc. The application of thermal
      interfacial materials and other physical methods can reliably improve the contact
      between joined surfaces and enhance interfacial thermal transport at the
      macroscale. With the growing importance of thermal management in micro/nanoscale
      devices, controlling and tuning the interfacial thermal resistance (ITR) at the
      nanoscale is an urgent task. This Review examines nanoscale interfacial thermal
      transport mainly from a theoretical perspective. Traditional theoretical models,
      multiscale models, and atomistic methodologies for predicting ITR are introduced.
      Based on the analysis and summary of the factors that influence ITR, new methods
      to control and reduce ITR at the nanoscale are described in detail. Furthermore,
      the challenges facing interfacial thermal management and the further progress
      required in this field are discussed.

PMID- 29226600
TI  - Loss of skills and onset patterns in neurodevelopmental disorders: Understanding
      the neurobiological mechanisms.
AB  - : Patterns of onset in Autism Spectrum Disorder, including a pattern that
      includes loss of previously acquired skills, have been identified since the first
      reports of the disorder. However, attempts to study such "regression" have been
      limited to clinical studies, that until recently mostly involved retrospective
      reports. The current report reflects discussion that occurred at an NIMH convened
      meeting in 2016 with the purpose of bridging clinical autism research with basic
      and translational work in this area. This summary describes the state of the
      field with respect to clinical studies, describing gaps in knowledge based on
      limited methods and prospective data collected. Biological mechanisms that have
      been shown to account for regression early in development in specific conditions
      are discussed, as well as potential mechanisms that have not yet been explored.
      Suggestions include use of model systems during the developmental period and
      cutting-edge methods, including non-invasive imaging that may afford
      opportunities for a better understanding of the neurobiological pathways that
      result in loss of previously-attained skills. Autism Res 2018, 11: 212-222. (c)
      2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY
      SUMMARY: Loss of previously acquired skills, or regression, has been reported in
      Autism Spectrum Disorder since Kanner's reports in the 1950's. The current report
      reflects discussion from an NIMH convened meeting in 2016 with the purpose of
      bridging clinical autism research with basic and translational work in this area.
      This summary describes the state of the field regarding clinical studies and
      suggests use of model systems during the developmental period and cutting-edge
      methods, for a better understanding of the neurobiological pathways that result
      in loss of previously-attained skills.

PMID- 29226602
TI  - First report of carp oedema virus infection of koi (Cyprinus carpio
      haematopterus) in the Republic of Korea.
AB  - Twenty-five koi (Cyprinus carpio haematopterus) bought from a wholesale fish
      market in Korea, showed lethargic behaviour and 100% mortality within 20 days.
      Carp oedema virus (CEV) was detected by PCR in all 25 koi. Results of detailed
      histopathological and clinical examinations of 17 koi indicated loss of body
      balance, severe infiltration of inflammatory cells into the inter-lamellar spaces
      of the gills and vacuolization and inclusion bodies in gill epithelial cells.
      Sequence analysis of PCR products of these koi showed up to 99% identity to the
      previously reported sequences, suggesting that the observed mass mortality
      resulted from koi sleepy disease (KSD) due to CEV infection. To the best of our
      knowledge, this study is the first report of KSD in the Republic of Korea.
      Partial sequences of 4a protein from the virus indicated that the present CEV
      detected in koi from Korea is more closely related to that from the UK and Poland
      than from Japan. The present findings indicate that the prevalence and spread of
      KSD must be closely monitored in both European and Asian countries to avoid
      potential economic losses to the global koi industry.

PMID- 29226603
TI  - Long TE STEAM and PRESS for estimating fat olefinic/methyl ratios and relative
      omega-3 fat content at 3T.
AB  - BACKGROUND: Fat olefinic/methyl ratios provide a measure of fat unsaturation. The
      methyl resonance linewidth is altered with the presence of omega-3 fat. PURPOSE:
      To optimize stimulated echo acquisition mode (STEAM) and point resolved
      spectroscopy (PRESS) echo times (TE) at 3T to 1) improve olefinic/methyl ratios
      and 2) enable relative omega-3 fat content assessment. STUDY TYPE: Technical
      development on phantoms and healthy volunteers. POPULATION: Nine edible oils and
      four healthy volunteers (tibial bone marrow). FIELD STRENGTH/SEQUENCE: STEAM
      (mixing time = 20 msec) and PRESS sequences at 3T. High-resolution oil spectra at
      16.5T. ASSESSMENT: 3T STEAM and PRESS olefinic/methyl ratios as a function of TE
      were compared to 16.5T measures for the oils, and to a literature-deduced value
      for tibial bone marrow. Oil methyl linewidths were calculated at each TE to
      investigate correlation with expected omega-3 fatty acid content. STATISTICAL
      TESTS: Percent differences were calculated between oil olefinic/methyl ratios
      obtained at 3T and 16.5T. Linear regression R2 values measured correlation of
      methyl linewidth to omega-3 content. RESULTS: STEAM, TE = 120 msec, resulted in
      average oil olefinic/methyl ratios that differ by about -4.8% compared to high
      resolution ratios. Tibial bone marrow olefinic/methyl ratios differ by -1.8%
      compared with literature-obtained ratios. PRESS, TE = 180 msec, resulted in oil
      ratios that differ by 7.8% and tibial bone marrow ratios that differ by 0.2%. A
      TE of 160 msec for both STEAM and PRESS enabled relative levels of oil omega-3
      fatty acid content to be estimated (R2 values >=0.9). DATA CONCLUSION: STEAM, TE
      = 120 msec (mixing time = 20 msec), and PRESS, TE = 180 msec, optimally estimated
      olefinic/methyl ratios. STEAM and PRESS, TE = 160 msec, enable relative oil omega
      3 fatty acid estimation from methyl linewidths. LEVEL OF EVIDENCE: 1 Technical
      Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

PMID- 29226604
TI  - An international qualitative study of functioning in autism spectrum disorder
      using the World Health Organization international classification of functioning,
      disability and health framework.
AB  - : This is the third in a series of four empirical studies designed to develop
      International Classification of Functioning, Disability and Health (ICF) Core
      Sets for Autism Spectrum Disorder (ASD). The present study aimed to describe
      functioning in ASD (as operationalized by the ICF) derived from the perspectives
      of diagnosed individuals, family members, and professionals. A qualitative study
      using focus groups and semi-structured interviews were conducted with 19
      stakeholder groups (N = 90) from Canada, India, Saudi Arabia, South Africa, and
      Sweden. Meaningful concepts from the focus groups and individual interviews were
      linked to ICF categories using a deductive qualitative approach with standardized
      linking procedures. The deductive qualitative content analysis yielded meaningful
      functioning concepts that were linked to 110 ICF categories across all four ICF
      components. Broad variation of environmental factors and activities and
      participation categories were identified in this study, while body functions
      consisted mainly of mental functions. Body structures were sparsely mentioned by
      the participants. Positive aspects of ASD included honesty, attention to detail,
      and memory. The experiences provided by international stakeholders support the
      need to understand individuals with ASD in a broader perspective, extending
      beyond diagnostic criteria into many areas of functioning and environmental
      domains. This study is part of a larger systematic effort that will provide the
      basis to define ICF Core Sets for ASD, from which assessment tools can be
      generated for use in clinical practice, research, and health care policy making.
      Autism Res 2018, 11: 463-475. (c) 2017 The Authors Autism Research published by
      International Society for Autism Research and Wiley Periodicals, Inc. LAY
      SUMMARY: The study findings support the need to understand the living experiences
      of individuals with Autism Spectrum Disorder (ASD) from a broader perspective,
      taking into account many areas of an individual's functioning and environment.
      The ICF can serve as foundation for exploring these living experiences more
      extensively by offering tools that enable wide variety of individual difficulties
      and strengths to be captured along with important environmental influences. As
      such, these tools can facilitate interventions that meet the needs and goals of
      the individual.

PMID- 29226605
TI  - Selective Coassembly of Aromatic Amino Acids to Fabricate Hydrogels with Light
      Irradiation-Induced Emission for Fluorescent Imprint.
AB  - Controlling the structural parameters in coassembly is crucial for the
      fabrication of multicomponent functional materials. Here a proof-of-concept study
      is presented to reveal the alpha-substituent effect of aromatic amino acids on
      their selective coassembly with bipyridine binders. With the assistance of X-ray
      scattering technique, it is found that individual packing in the solid state as
      well as bulky effect brought by alpha-substitution determines the occurrence of
      coassembly. A well-performed hydrogels based on the complexation between certain
      aromatic amino acids and bipyridine units are successfully constructed, providing
      unprecedented smart materials with light irradiation-triggered luminescence. Such
      hydrogels without the phase separation and photobleaching during light
      irradiation are able to behave fluorescent imprint materials. This study provides
      a suitable protocol in rationally designing amino acid residues of short peptides
      for fabricating self-assembled multicomponent materials. In addition, this
      protocol is useful in screening potential functional materials on account of
      diverse self-assembly behavior.

PMID- 29226606
TI  - The challenges of implementing an integrated One Health surveillance system in
      Australia.
AB  - As 75 per cent of emerging infectious diseases are of animal origin, a One Health
      approach that integrates the health of humans, animals and the environment could
      provide an earlier opportunity for zoonotic disease detection and prevention. In
      Australia, human, animal and ecological health are managed by separate sectors
      with limited communication. This study aims to explore how professionals in these
      fields perceive a One Health approach to zoonotic disease surveillance, aiming to
      identify the challenges to the implementation of an integrated system in
      Australia. Using a qualitative research method, ten semistructured interviews
      were conducted with academic experts to gain insight into the possibility of
      developing an integrated surveillance system in Australia. A thematic analysis of
      the data was undertaken. Findings showed the absence of a clear definition and
      subsequent vision for the future of One Health act as a barrier to
      interdisciplinary collaboration, and that siloed approaches by different sectors
      restrict the ability for professionals to work collaboratively across
      disciplines. An understanding of disease transmission was considered by
      participants to be a necessary requirement for a successful One Health approach.
      Finally, participants considered political will an essential requirement for the
      integration of surveillance systems. This study demonstrates that for a One
      Health approach to be implemented in an Australian setting, those working in the
      fields of human, animal and ecological health must agree on several aspects. The
      establishment of a formal governance body with representatives from each sector
      could assist in overcoming long-standing barriers of privacy and distrust.
      Further, developing interdisciplinary training in One Health concepts for
      medical, environmental and veterinary students may encourage cross-disciplinary
      collaboration. Finally, demonstrating to policymakers the economic benefit of
      improved and timely detection of zoonoses may help in facilitating a structured
      One Health approach to disease surveillance in Australia.

PMID- 29226607
TI  - Comparison of the Convolution algorithm with TMR10 for Leksell Gamma knife and
      dosimetric verification with radiochromic gel dosimeter.
AB  - The Convolution algorithm, implemented in Leksell GammaPlan(r) ver. Here, 10, is
      the first algorithm for Leksell Gamma Knife that takes heterogeneities into
      account and models dose build-up effects close to tissue boundaries. The aim of
      this study was preliminary comparison of the Convolution and TMR10 algorithms for
      real clinical cases and dosimetric verification of the algorithms, using
      measurements in a phantom. A total of 25 patients involved in comparison of the
      Convolution and TMR10 algorithms were divided into three groups: patients with
      benign tumors close to heterogeneities, patients with functional disorders, and
      patients with tumors located far from heterogeneities. Differences were observed
      especially in the group of patients with tumors close to heterogeneities, where
      the difference in maximal dose to critical structures for the Convolution
      algorithm was up to 15% compared to the TMR10 algorithm. Dosimetric verification
      of the algorithm was performed, using a radiochromic gel dosimeter based on
      Turnbull blue dye in a special heterogeneous phantom. Relative dose distributions
      measured with the radiochromic gel dosimeter agreed very well with both the TMR10
      and Convolution calculations. We observed small discrepancies in the direction in
      which the largest inhomogeneity was positioned. Verification results indicated
      that the Convolution algorithm provides a different dose distribution, especially
      in regions close to heterogeneities and particularly for lower isodose volumes.
      However, the results obtained with gamma analyses in the gel dosimetry experiment
      did not verify the assumption that the Convolution algorithm provides more
      accurate dose calculation.

PMID- 29226608
TI  - Internal adaptation of resin composite restorations with different thicknesses of
      glass ionomer cement lining.
AB  - AIM: The aim of the present study was to investigate the effect of the thin or
      thick placement of resin-modified glass ionomer cement (RMGIC) lining on the
      adaptation of resin composite restorations bonded with two types of adhesive.
      METHODS: Sixty deep occlusal cavities were prepared and divided into two groups:
      etch-and-rinse adhesive (Single Bond 2) or self-etching adhesive (Clearfil SE
      Bond). Specimens were further divided into three subgroups: no lining (control),
      lined with 0.5 mm-thin RMGIC, or lined with 1 mm-thick RMGIC (Vitrebond). Each
      cavity was bonded, restored with resin composite, and sectioned to obtain two
      specimens. One specimen was stained with 2% methylene blue, and dye staining at
      the pulpal floor and cavity walls was calculated. Other specimens were
      investigated for micro-gap formation using scanning electron microscopy (SEM).
      RESULTS: For Single Bond 2, dye staining was not significantly different among
      the three groups. For Clearfil SE Bond, lining absence showed the lowest dye
      staining at the pulpal floor. Dye staining of 0.5 mm-thin RMGIC significantly
      increased, but 1 mm-thick RMGIC tended to reduce dye staining. Comparing the two
      adhesives, there was no significant difference in dye staining. From the SEM
      images, micro-gaps were more frequently observed in the 0.5 mm-thin lining
      groups. CONCLUSIONS: RMGIC should be placed as a thick lining, if indicated.

PMID- 29226609
TI  - A P2-Type Layered Superionic Conductor Ga-Doped Na2 Zn2 TeO6 for All-Solid-State
      Sodium-Ion Batteries.
AB  - Here, a P2-type layered Na2 Zn2 TeO6 (NZTO) is reported with a high Na+ ion
      conductivity ~0.6*10-3  S cm-1 at room temperature (RT), which is comparable to
      the currently best Na1+n Zr2 Sin P3-n O12 NASICON structure. As small amounts of
      Ga3+ substitutes for Zn2+ , more Na+ vacancies are introduced in the interlayer
      gaps, which greatly reduces strong Na+ -Na+ coulomb interactions. Ga-substituted
      NZTO exhibits a superionic conductivity of ~1.1*10-3  S cm-1 at RT, and excellent
      phase and electrochemical stability. All solid-state batteries have been
      successfully assembled with a capacity of ~70 mAh g-1 over 10 cycles with a rate
      of 0.2 C at 80  degrees C. 23 Na nuclear magnetic resonance (NMR) studies on
      powder samples show intra-grain (bulk) diffusion coefficients DNMR on the order
      of 12.35*10-12  m2  s-1 at 65  degrees C that corresponds to a conductivity
      sigmaNMR of 8.16*10-3  S cm-1 , assuming the Nernst-Einstein equation, which thus
      suggests a new perspective of fast Na+ ion conductor for advanced sodium ion
      batteries.

PMID- 29226610
TI  - Nuclear magnetic resonance-based metabolomics identifies phenylalanine as a novel
      predictor of incident heart failure hospitalisation: results from PROSPER and
      FINRISK 1997.
AB  - AIMS: We investigated the association between quantified metabolite, lipid and
      lipoprotein measures and incident heart failure hospitalisation (HFH) in the
      elderly, and examined whether circulating metabolic measures improve HFH
      prediction. METHODS AND RESULTS: Overall, 80 metabolic measures from the
      PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were
      measured by proton nuclear magnetic resonance spectroscopy (n = 5341; 182 HFH
      events during 2.7-year follow-up). We repeated the work in FINRISK 1997 (n =
      7330; 133 HFH events during 5-year follow-up). In PROSPER, the circulating
      concentrations of 13 metabolic measures were found to be significantly different
      in those who were later hospitalised for heart failure after correction for
      multiple comparisons. These included creatinine, phenylalanine, glycoprotein
      acetyls, 3-hydroxybutyrate, and various high-density lipoprotein measures. In Cox
      models, two metabolites were associated with risk of HFH after adjustment for
      clinical risk factors and N-terminal pro-B-type natriuretic peptide (NT-proBNP):
      phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10-1.53; P
      = 0.002] and acetate (HR 0.81, 95% CI 0.68-0.98; P = 0.026). Both were retained
      in the final model after backward elimination. Compared to a model with
      established risk factors and NT-proBNP, this model did not improve the C-index
      but did improve the overall continuous net reclassification index (NRI 0.21; 95%
      CI 0.06-0.35; P = 0.007) due to improvement in classification of non-cases (NRI
      0.14; 95% CI 0.12-0.17; P < 0.001). Phenylalanine was replicated as a predictor
      of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03-1.48; P = 0.023). CONCLUSION: Our
      findings identify phenylalanine as a novel predictor of incident HFH, although
      prediction gains are low. Further mechanistic studies appear warranted.

PMID- 29226611
TI  - Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical
      Nucleic Acids through Lipid-Tail DNA Modifications.
AB  - Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform
      for gene regulation and immunomodulation due to their biocompatibility,
      chemically tunable structures, and ability to enter cells rapidly without the
      need for ancillary transfection agents. Such structures consist of small (<100
      nm) liposomal cores functionalized with a dense, highly oriented nucleic acid
      shell, both of which are key components in facilitating their biological
      activity. Here, the properties of LSNAs synthesized using conventional methods,
      anchoring cholesterol terminated oligonucleotides into a liposomal core, are
      compared to LSNAs made by directly modifying the surface of a liposomal core
      containing azide-functionalized lipids with dibenzocyclooctyl-terminated
      oligonucleotides. The surface densities of the oligonucleotides are measured for
      both types of LSNAs, with the lipid-modified structures having approximately
      twice the oligonucleotide surface coverage. The stabilities and cellular uptake
      properties of these structures are also evaluated. The higher density, lipid
      functionalized structures are markedly more stable than conventional cholesterol
      based structures in the presence of other unmodified liposomes and serum proteins
      as evidenced by fluorescence assays. Significantly, this new form of LSNA
      exhibits more rapid cellular uptake and increased sequence-specific toll-like
      receptor activation in immune reporter cell lines, making it a promising
      candidate for immunotherapy.

PMID- 29226612
TI  - Glutaraldehyde cross-linking increases the stability of Lumbricus terrestris
      erythrocruorin.
AB  - Since donated red blood cells must be constantly refrigerated, they are not
      available in remote areas and battlefields. We have previously shown that the
      hemoglobin of the earthworm Lumbricus terrestris (LtEc) is an effective and safe
      substitute for donated blood that is stable enough to be stored for long periods
      at the relatively high temperatures that may be encountered in remote areas. The
      goal of this study was to further increase the thermal stability of LtEc by
      covalently cross-linking LtEc with glutaraldehyde (gLtEc). Our results show that
      the melting temperatures of the gLtEc samples steadily increase as the molar
      ratio of glutaraldehyde to heme increases (from Tm  = 57 degrees C for native
      LtEc up to Tm  = 68 degrees C at a ratio of 128:1). In addition, while native
      LtEc is susceptible to subunit dissociation at alkaline pH (8-10), cross-linking
      with glutaraldehyde completely prevents dissociation of gLtEc at pH 10.
      Increasing the molar ratio of glutaraldehyde:heme also significantly increased
      the oxygen affinity of gLtEc, but this effect was decreased by cross-linking
      gLtEc in the deoxygenated T state. Finally, while gLtEc samples cross-linked at
      low G:H ratios (e.g., 2:1) exhibited slight increases in oxidation rate in Tris
      buffer, no significant difference in oxidation rate was observed between native
      LtEc and the gLtEc samples in Ringer's Solution, which contains antioxidants.
      Overall, cross-linking LtEc with glutaraldehyde significantly increases its
      thermal and structural stability without any loss of function, making gLtEc an
      attractive blood substitute for deployment in remote areas and battlefields. (c)
      2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:521-528,
      2018.

PMID- 29226613
TI  - Large-scale culture of a megakaryocytic progenitor cell line with a single-use
      bioreactor system.
AB  - The increasing application of regenerative medicine has generated a growing
      demand for stem cells and their derivatives. Single-use bioreactors offer an
      attractive platform for stem cell expansion owing to their scalability for large
      scale production and feasibility of meeting clinical-grade standards. The current
      work evaluated the capacity of a single-use bioreactor system (1 L working
      volume) for expanding Meg01 cells, a megakaryocytic (MK) progenitor cell line.
      Oxygen supply was provided by surface aeration to minimize foaming and orbital
      shaking was used to promote oxygen transfer. Oxygen transfer rates (kL a) of
      shaking speeds 50, 100, and 125 rpm were estimated to be 0.39, 1.12, and 10.45 h
      1 , respectively. Shaking speed was a critical factor for optimizing cell growth.
      At 50 rpm, Meg01 cells exhibited restricted growth due to insufficient mixing. A
      negative effect occurred when the shaking speed was increased to 125 rpm, likely
      caused by high hydrodynamic shear stress. The bioreactor culture achieved the
      highest growth profile when shaken at 100 rpm, achieving a total expansion rate
      up to 5.7-fold with a total cell number of 1.2 +/- 0.2 * 109 cells L-1 . In
      addition, cells expanded using the bioreactor system could maintain their potency
      to differentiate following the MK lineage, as analyzed from specific surface
      protein and morphological similarity with the cells grown in the conventional
      culturing system. Our study reports the impact of operational variables such as
      shaking speed for growth profile and MK differentiation potential of a progenitor
      cell line in a single-use bioreactor. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:362-369, 2018.

PMID- 29226615
TI  - Intestinal organoids containing poly(lactic-co-glycolic acid) nanoparticles for
      the treatment of inflammatory bowel diseases.
AB  - Inflammatory bowel disease (IBD) causes inflammation to the gastrointestinal
      tract. Local administration of anti-inflammatory drugs such as 5-aminosalicylic
      acid (5-ASA) can alleviate the symptoms of IBD. The application of nanoparticles
      for IBD treatment in direct rectal administration showed high drug availability
      and treatment efficacy. However, relying on size-dependent adsorption of smaller
      particles is not sufficient for making the formulation capable of targeting.
      Intestinal organoids can improve the functionality of the nanoparticles due to
      their ability to adsorb small nanoparticle inside the lumen and attach to the
      damaged area. In this study, intestinal organoids were used as carriers of 5-ASA
      loaded poly(lactic-co-glycolic acid) nanoparticles. The nanoparticle sizes,
      confirmed by scanning electron microscopy, were 200-300 nm and the zeta potential
      were negative. The nanoparticles did not have any noticeable pernicious effect on
      organoid growth and viability. After mixing the nanoparticles with Matrigel and
      organoids, Rhodamine B loaded inside the nanoparticles was highly detected inside
      the organoid's lumen after 3 days by confocal fluorescent microscopy and no
      longer detected in the lumen after day 4. It may be attributed to the ability of
      the lumen to digest particles. Thus, the organoid Trojan horse system is a
      possible approach for delivering drugs to inflamed areas. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 876-886, 2018.

PMID- 29226616
TI  - Clinical characteristics of maternal mental health service users treated with
      mood stabilizing or antipsychotic medication.
AB  - INTRODUCTION: We aimed to investigate the characteristics of pregnant women who
      required either mood stabilizer or antipsychotic treatment. These women requiring
      such treatment are likely to be more mentally unwell and thus carry a higher
      burden of comorbidities associated with poor pregnancy outcomes. METHODS: This
      retrospective review investigated the common characteristics of pregnant women
      who were prescribed with antipsychotics or mood stabilizers under a major city's
      public maternal mental health service. Demographic data, pregnancy factors and
      prenatal care, stressors and support, concurrent medical and substance abuse
      problems, and ongoing maternal mental health issues were recorded. RESULTS: Most
      pregnancies were unplanned. Commonly, social stressors, medical problems, and
      substance use were identified. The most common diagnosis was bipolar disorder.
      DISCUSSION: Pregnant women requiring treatment with mood stabilizers or
      antipsychotics are a complex clinical population, with multiple risk factors for
      negative pregnancy outcome, before even considering the potential risk from
      psychotropic agents and mental illness itself. Obtaining reliable data about
      substance use and medication compliance remains problematic.

PMID- 29226617
TI  - Activation of glucagon-like peptide-1 receptors in the nucleus accumbens
      attenuates cocaine seeking in rats.
AB  - Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1)
      receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release
      in the nucleus accumbens (NAc). However, no studies have examined the role of NAc
      GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model
      of relapse. Here, we show that systemic infusion of a behaviorally relevant dose
      of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with
      neurons and astrocytes in the NAc. Administration of exendin-4 directly into the
      NAc core and shell subregions significantly attenuated cocaine priming-induced
      reinstatement of drug-seeking behavior. These effects were not due to deficits in
      operant responding or suppression of locomotor activity as intra-accumbal exendin
      4 administration had no effect on sucrose-seeking behavior. To determine the
      effects of GLP-1 receptor activation on neuronal excitability, exendin-4 was bath
      applied to ex vivo NAc slices from cocaine-experienced and saline-experienced
      rats following extinction of cocaine-taking behavior. Exendin-4 increased the
      frequency of action potential firing of NAc core and shell medium spiny neurons
      in cocaine-experienced rats while no effect was observed in saline controls. In
      contrast, exendin-4 did not affect the frequency or amplitude of spontaneous
      excitatory postsynaptic currents or alter the paired-pulse ratios of evoked
      excitatory postsynaptic currents. These effects were not associated with altered
      expression of GLP-1 receptors in the NAc following cocaine self-administration.
      Taken together, these findings indicate that increased activation of GLP-1
      receptors in the NAc during cocaine abstinence increases intrinsic, but not
      synaptic, excitability of medium spiny neurons and is sufficient to reduce
      cocaine-seeking behavior.

PMID- 29226618
TI  - Enteroinsular hormones in two siblings with Donohue syndrome and complete leptin
      deficiency.
AB  - The main biochemical hallmark of the rare and lethal condition of Donohue
      syndrome (DS) is hyperinsulinemia. The roles of the gut and other pancreatic
      hormones involved in glucose metabolism, satiety and energy expenditure have not
      been previously reported in DS. Two siblings with genetically confirmed DS and
      extremely low weight underwent a mixed meal (MM) test where pancreatic hormones
      insulin, C-peptide, glucagon, active amylin, pancreatic polypeptide (PP) as well
      as gut hormones active glucagon-like peptide 1 (GLP-1), glucose-dependent
      insulinotropic peptide (GIP), ghrelin, peptide YY (PYY) and leptin were analyzed
      using a Multiplex assay. Results were compared to those of 2 pediatric controls.
      As expected, concentrations of insulin, C-peptide and amylin were very high in DS
      cases. The serum glucagon concentration was undetectable at the time of
      hypoglycemia. GIPs concentrations were lower in the DS, however, this was not
      mimicked by the other incretin, GLP-1. Ghrelin concentrations were mainly
      undetectable (<13.7 pg/mL) in all participants. DS cases had higher PYY and
      dampened PP concentrations. Leptin levels remained completely undetectable
      (<137.0 pg/mL). Patients with DS have extremely high amylin levels, completely
      undetectable serum glucagon and leptin levels with abnormal satiety regulating
      hormone PP with a relatively normal ghrelin response during a MM test. The low
      serum GIP might be acting as physiological brake on insulin secretion. The
      undetectable serum leptin levels suggest the potential of using leptin analogues
      as therapy for DS patients.

PMID- 29226619
TI  - 1D Nanomaterials: Design, Synthesis, and Applications in Sodium-Ion Batteries.
AB  - Sodium-ion batteries (SIBs) have received extensive attention as ideal candidates
      for large-scale energy storage systems (ESSs) owing to the rich resources and low
      cost of sodium (Na). However, the larger size of Na+ and the less negative redox
      potential of Na+ /Na result in low energy densities, short cycling life, and the
      sluggish kinetics of SIBs. Therefore, it is necessary to develop appropriate Na
      storage electrode materials with the capability to host larger Na+ and fast ion
      diffusion kinetics. 1D materials such as nanofibers, nanotubes, nanorods, and
      nanowires, are generally considered to be high-capacity and stable electrode
      materials, due to their uniform structure, orientated electronic and ionic
      transport, and strong tolerance to stress change. Here, the synthesis of 1D
      nanomaterials and their applications in SIBs are reviewed. In addition, the
      prospects of 1D nanomaterials on energy conversion and storage as well as the
      development and application orientation of SIBs are presented.

PMID- 29226620
TI  - Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic
      and intestinal in vitro cell models.
AB  - Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an
      analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of
      primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid
      (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid
      efflux via activating FXR-mediated mechanisms in a physiologically relevant in
      vitro cell system, Sandwich-cultured Transporter Certified TM human primary
      hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in
      combination with OCA in SCHH. UDCA (<=100 MUmol/L) alone did not inhibit CYP7A1
      mRNA, and thus, no reduction in the endogenous bile acid pool observed. UDCA
      <=100 MUmol/L concomitantly administered with 0.1 MUmol/L OCA had no effect on
      bile acid synthesis beyond what was observed with OCA alone. Furthermore, this
      study evaluated human Caco-2 cells (clone C2BBe1) as in vitro intestinal models.
      Glycine conjugate of OCA increased mRNA levels of FXR target genes in Caco-2
      cells, FGF-19, SHP, OSTalpha/beta, and IBABP, but not ASBT, in a concentration
      dependent manner, while glycine conjugate of UDCA had no effect on the expression
      of these genes. The results suggested that UDCA <=100 MUmol/L did not activate
      FXR in human primary hepatocytes or intestinal cell line Caco-2. Thus, co
      administration of UDCA with OCA did not affect OCA-dependent pharmacological
      effects.

PMID- 29226621
TI  - Cenerimod, a novel selective S1P1 receptor modulator with unique signaling
      properties.
AB  - Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating
      lymphocytes within lymph nodes, thereby preventing potentially pathogenic
      autoimmune cells from exiting into the blood stream and reaching inflamed
      tissues. S1P1 receptor modulation may thus offer potential to treat various
      autoimmune diseases. The first nonselective S1P1-5 receptor modulator
      FTY720/fingolimod/Gilenya(r) has successfully demonstrated clinical efficacy in
      relapsing forms of multiple sclerosis. However, cardiovascular, hepatic, and
      respiratory side-effects were reported and there is a need for novel S1P1
      receptor modulators with better safety profiles. Here, we describe the discovery
      of cenerimod, a novel, potent and selective S1P1 receptor modulator with unique
      S1P1 receptor signaling properties and absence of broncho- and vasoconstrictor
      effects ex vivo and in vivo. Cenerimod dose-dependently lowered circulating
      lymphocyte counts in rats and mice after oral administration and effectively
      attenuated disease parameters in a mouse experimental autoimmune encephalitis
      (EAE) model. Cenerimod has potential as novel therapy with improved safety
      profile for autoimmune diseases with high unmet medical need.

PMID- 29226622
TI  - PDE4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E
      synthase-1 by a mechanism dependent on MAP kinase phosphatase-1.
AB  - Phosphodiesterase-4 (PDE4) inhibitors have recently been introduced to the
      treatment of COPD and psoriatic arthritis. Microsomal prostaglandin E synthase-1
      (mPGES-1) is an inducible enzyme synthesizing PGE2 , the most abundant prostanoid
      related to inflammation and inflammatory pain. mPGES-1 is a potential drug target
      for novel anti-inflammatory treatments aiming at an improved safety profile as
      compared to NSAIDs. Here we investigated the effect of the PDE4 inhibitor
      rolipram on the expression of mPGES-1 in macrophages; and a potential mediator
      role in the process for MAP kinase phosphatase-1 (MKP-1) which is an endogenous
      factor limiting the activity of the proinflammatory MAP kinases p38 and JNK. The
      expression of mPGES-1 was decreased, whereas that of MKP-1 was enhanced by
      rolipram in wild-type murine macrophages. Interestingly, rolipram did not reduce
      mPGES-1 expression in peritoneal macrophages from MKP-1-deficient mice. A reduced
      phosphorylation of JNK, but not p38 MAP kinase, was specifically associated with
      the decreased expression of mPGES-1. Accordingly, mPGES-1 expression was
      suppressed by JNK but not p38 inhibitor. These findings underline the
      significance of the increased MKP-1 expression and decreased JNK phosphorylation
      associated with the downregulated expression of mPGES-1 by PDE4 inhibitors in
      inflammation.

PMID- 29226624
TI  - Burden of health-care costs for patients with heparin replacement for colorectal
      EMR in Japan.

PMID- 29226623
TI  - Distortion of KB estimates of endothelin-1 ETA and ETB receptor antagonists in
      pulmonary arteries: Possible role of an endothelin-1 clearance mechanism.
AB  - Dual endothelin ETA and ETB receptor antagonists are approved therapy for
      pulmonary artery hypertension (PAH). We hypothesized that ETB receptor-mediated
      clearance of endothelin-1 at specific vascular sites may compromise this targeted
      therapy. Concentration-response curves (CRC) to endothelin-1 or the ETB agonist
      sarafotoxin S6c were constructed, with endothelin receptor antagonists, in
      various rat and mouse isolated arteries using wire myography or in rat isolated
      trachea. In rat small mesenteric arteries, bosentan displaced endothelin-1 CRC
      competitively indicative of ETA receptor antagonism. In rat small pulmonary
      arteries, bosentan 10 MUmol L-1 left-shifted the endothelin-1 CRC, demonstrating
      potentiation consistent with antagonism of an ETB receptor-mediated endothelin-1
      clearance mechanism. Removal of endothelium or L-NAME did not alter the EC50 or
      Emax of endothelin-1 nor increase the antagonism by BQ788. In the presence of
      BQ788 and L-NAME, bosentan displayed ETA receptor antagonism. In rat trachea (ETB
      ), bosentan was a competitive ETB antagonist against endothelin-1 or sarafotoxin
      S6c. Modeling showed the importance of dual receptor antagonism where the potency
      ratio of ETA to ETB antagonism is close to unity. In conclusion, the rat
      pulmonary artery is an example of a special vascular bed where the resistance to
      antagonism of endothelin-1 constriction by ET dual antagonists, such as bosentan
      or the ETB antagonist BQ788, is possibly due to the competition of potentiation
      of endothelin-1 by blockade of ETB -mediated endothelin-1 clearance located on
      smooth muscle and antagonism of ETA - and ETB -mediated contraction. This
      conclusion may have direct application for the efficacy of endothelin-1
      antagonists for treating PAH.

PMID- 29226625
TI  - Identification of an antibody-based immunoassay for measuring direct target
      binding of RIPK1 inhibitors in cells and tissues.
AB  - Therapies that suppress RIPK1 kinase activity are emerging as promising
      therapeutic agents for the treatment of multiple inflammatory disorders. The
      ability to directly measure drug binding of a RIPK1 inhibitor to its target is
      critical for providing insight into pharmacokinetics, pharmacodynamics, safety
      and clinical efficacy, especially for a first-in-class small-molecule inhibitor
      where the mechanism has yet to be explored. Here, we report a novel method for
      measuring drug binding to RIPK1 protein in cells and tissues. This TEAR1 (Target
      Engagement Assessment for RIPK1) assay is a pair of immunoassays developed on the
      principle of competition, whereby a first molecule (ie, drug) prevents the
      binding of a second molecule (ie, antibody) to the target protein. Using the
      TEAR1 assay, we have validated the direct binding of specific RIPK1 inhibitors in
      cells, blood and tissues following treatment with benzoxazepinone (BOAz) RIPK1
      inhibitors. The TEAR1 assay is a valuable tool for facilitating the clinical
      development of the lead RIPK1 clinical candidate compound, GSK2982772, as a first
      in-class RIPK1 inhibitor for the treatment of inflammatory disease.

PMID- 29226627
TI  - Data visualizations to detect systematic errors in laboratory assay results.
AB  - The measurement of concentrations of drugs and endogenous substances is widely
      used in basic and clinical pharmacology research and service tasks. Using data
      science-derived visualizations of laboratory data, it is demonstrated on a real
      life example that basic statistical exploration of laboratory assay results or
      advised standard visual methods of data inspection may fall short in detecting
      systematic laboratory errors. For example, data pathologies such as generating
      always the same value in all probes of a particular assay run may pass undetected
      when using standard methods of data quality check. It is shown that the use of
      different data visualizations that emphasize different views of the data may
      enhance the detection of systematic laboratory errors. A dotplot of single data
      in the order of assay is proposed that provides an overview on the data range,
      outliers and a particular type of systematic errors where similar values are
      wrongly measured in all probes.

PMID- 29226626
TI  - Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of
      RIPK1 inhibitor GSK2982772 in healthy volunteers.
AB  - GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase
      1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in
      human study evaluated safety, tolerability, pharmacokinetics (PK), and
      exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy
      male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind
      study. In Part A, subjects received single ascending doses of GSK2982772 (0.1-120
      mg) or placebo in a crossover design during each of 4 treatment periods. In Part
      B, subjects received repeat doses of GSK2982772 (20 mg once daily [QD] to up to
      120 mg twice daily [BID]) or placebo for 14 days. Part C was an open-label
      relative bioavailability study comparing 20-mg tablets vs capsules. Safety,
      tolerability, pharmacokinetics (PK), RIPK1 target engagement (TE), and
      pharmacodynamics (PD) were assessed. The most common adverse events (AEs) were
      contact dermatitis and headache. Most AEs were mild in intensity, and there were
      no deaths or serious AEs. The PK of GSK2982772 was approximately linear over the
      dose range studied (up to 120 mg BID). There was no evidence of drug accumulation
      upon repeat dosing. Greater than 90% RIPK1 TE was achieved over a 24-hour period
      for the 60-mg and 120-mg BID dosing regimens. Single and repeat doses of
      GSK2982772 were safe and well tolerated. PK profiles showed dose linearity. The
      high levels of RIPK1 TE support progression into Phase II clinical trials for
      further clinical development.

PMID- 29226629
TI  - Surfactant-Dependent Charge Transfer between Polyoxometalates and Single-Walled
      Carbon Nanotubes: A Fluorescence Spectroscopic Study.
AB  - Hybridizations of redox-active polyoxometalates (POMs) with single-walled carbon
      nanotubes (SWNTs) have been widely investigated for their diverse applications.
      For the purpose of constructing high-quality electronic devices, controlling
      charge transfer within POM/SWNT hybrids is an inevitable issue. As determined by
      means of fluorescence spectroscopy, electron transfer between SWNTs and a common
      POM dopant, phosphomolybdic acid (PMo12 ), can be tuned simply by an alteration
      of nanotube surfactant type from anionic to nonionic. The mechanism is attributed
      to the influence of surfactant type on the stabilization of the electron donor
      acceptor hybrid and effect of surfactant-nanotube interactions. These results
      will be important to control charge-transport behavior in nanohybrids consisting
      of carbon nanotubes.

PMID- 29226628
TI  - Modeling of prolactin response following dopamine D2 receptor antagonists in
      rats: can it be translated to clinical dosing?
AB  - Prolactin release is a side effect of antipsychotic therapy with dopamine
      antagonists, observed in rats as well as humans. We examined whether two
      semimechanistic models could describe prolactin response in rats and subsequently
      be translated to predict pituitary dopamine D2 receptor occupancy and plasma
      prolactin concentrations in humans following administration of paliperidone or
      remoxipride. Data on male Wistar rats receiving single or multiple doses of
      risperidone, paliperidone, or remoxipride was described by two semimechanistic
      models, the precursor pool model and the agonist-antagonist interaction model.
      Using interspecies scaling approaches, human D2 receptor occupancy and plasma
      prolactin concentrations were predicted for a range of clinical paliperidone and
      remoxipride doses. The predictions were compared with corresponding observations
      described in literature as well as with predictions from published models
      developed on human data. The pool model could predict D2 receptor occupancy and
      prolactin response in humans following single doses of paliperidone and
      remoxipride. Tolerance of prolactin release was predicted following multiple
      doses. The interaction model underpredicted both D2 receptor occupancy and
      prolactin response. Prolactin elevation may be deployed as a suitable biomarker
      for interspecies translation and can inform the clinical safe and effective dose
      range of antipsychotic drugs. While the pool model was more predictive than the
      interaction model, it overpredicted tolerance on multiple dosing. Shortcomings of
      the translations reflect the need for better mechanistic models.

PMID- 29226630
TI  - Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling
      for management of acne scarring: A split-face clinical and histologic comparison.
AB  - BACKGROUND: Minimally invasive procedures provide effective, safe, relatively
      long-lasting, and natural results without large damage to the skin. A combination
      treatment is considered an approach that includes at least 2 different and
      unrelated modalities. OBJECTIVES: This study aims to evaluate the use and
      effectiveness of some combined minimally invasive procedures for management of
      acne scarring. PATIENTS/METHODS: Twenty-four volunteers with postacne atrophic
      scars were randomly divided into 3 equal groups according to performed procedure
      on each side of the face (microneedling by dermaroller alone or combined with
      platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and
      received 6 bi-weekly sessions of treatment. Photography and punch biopsies were
      taken before and after 3 months of treatment for clinical, histological, and
      histometrical evaluation. RESULTS: Combined treatment of dermaroller and PRP or
      dermaroller and TCA 15% showed significant improvement when compared with
      dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed
      statistically significant increase in studied groups, mainly after dermaroller
      and TCA 15%. Moreover, the 3 studied groups showed more organized collagen
      bundles and newly formed collagen formation and markedly decreased abnormal
      elastic fibers. CONCLUSIONS: Based on the clinical, histometrical, and
      histochemical assessment, inspite that most volunteers showed significant
      improvement after treatment, however, the combined use of dermaroller and TCA 15%
      was more effective in postacne atrophic scars than the use of dermaroller and PRP
      or dermaroller only.

PMID- 29226631
TI  - Novel compound heterozygous mutations in GPT2 linked to microcephaly, and
      intellectual developmental disability with or without spastic paraplegia.
AB  - We here describe novel compound heterozygous missense variants,
      NM_133443:c.[400C>T] and NM_133443:[1435G>A], in the glutamic-pyruvic
      transaminase 2 (GPT2) gene in a large consanguineous family with two affected
      siblings diagnosed with microcephaly intellectual disability and developmental
      delay (IDD). In addition to these clinical phenotypes, the male sibling has
      spastic paraplegia, and the female sibling has epilepsy. Their four extended
      family members have IDD and microcephaly. Both of these variants, c.400C>T
      (p.R134C) and c.1435G>A (p.V479M), reside in the pyridoxal phosphate-dependent
      aminotransferase domain. The missense variants affect highly conserved amino
      acids and are classified to be disease-causing by meta-SVM. The candidate
      variants were not found in the Exome Aggregation Consortium (ExAC) dataset or in
      dbSNP. Both GPT2 variants have an allele frequency of 0% (0/ ~ 600) in the whole
      exome sequenced Turkish cohort. Upon Sanger sequencing, we confirmed these
      mutations in all affected family members and showed that the index patient and
      his affected sister inherited one mutant allele from each unaffected parent. To
      the best of our knowledge, this is the first family in which a novel compound
      heterozygous variant in the GPT2 gene was identified.

PMID- 29226632
TI  - Novel bovine-associated pVAPN plasmid type in Rhodococcus equi identified from
      lymph nodes of slaughtered cattle and lungs of people living with HIV/AIDS.
AB  - Rhodococcus equi is a well-recognized Gram-positive intracellular facultative
      bacterium that is opportunistic in nature, which causes pyogranulomatous
      infections in humans and multiple host animals. The pathogenicity of the
      microorganism has been attributed to the presence of plasmid-encoded virulence
      associated proteins (Vap). To date, three host-associated virulence plasmid types
      of R. equi have been identified as follows: the circular pVAPA and pVAPB,
      related, respectively, to equine and porcine isolates, and a recently described
      linear pVAPN plasmid associated with bovine strains, although these three types
      are found in human isolates. Recent phylogenomic studies support the evidence
      that human R. equi infection is zoonotically acquired. Nevertheless, data
      regarding distribution and prevalence of the host-adapted virulence plasmid types
      of R. equi isolated from meat animals are scarce or unnoticed. Here, the three
      host-associated virulence plasmid types (pVAPA, pVAPB, and pVAPN) were
      investigated in 154 R. equi isolates recovered from lymph nodes of cattle with
      lymphadenitis (n = 31), faeces of cattle without enteric signs (n = 49), as well
      as different clinical specimens from human patients (n = 74). The analysis of
      virulence profile of 74 R. equi from humans revealed six (8.1%) isolates pVAPB
      (type 8), two (2.7%) pVAPN, and one (1.3%) pVAPB (type 11), all of which were
      from lung samples from people living with HIV/AIDS. From the lymph node samples
      of cattle, 41.9% (13 of 31) isolates revealed pVAPN type, whereas all isolates
      from faecal samples were negative for three host-associated types. Here, recently
      described bovine-associated pVAPN type was detected in R. equi isolates recovered
      from the lungs of people living with HIV/AIDS and lymph nodes from slaughtered
      cattle intended for human consumption; a finding that represents a public health
      concern, mainly in countries where undercooked or raw meat are traditionally
      consumed.

PMID- 29226633
TI  - Characterization of Membrane Patch-Ion Channel Probes for Scanning Ion
      Conductance Microscopy.
AB  - Integration of dual-barrel membrane patch-ion channel probes (MP-ICPs) to
      scanning ion conductance microscopy (SICM) holds promise of providing a
      revolutionized approach of spatially resolved chemical sensing. A series of
      experiments are performed to further the understanding of the system and to
      answer some fundamental questions, in preparation for future developments of this
      approach. First, MP-ICPs are constructed that contain different types of ion
      channels including transient receptor potential vanilloid 1 and large conductance
      Ca2+ -activated K+ channels to establish the generalizability of the methods.
      Next, the capability of the MP-ICP platforms in single ion channel activity
      measurements is proved. In addition, the interplay between the SICM barrel and
      the ICP barrel is studied. For ion channels gated by uncharged ligands, channel
      activity at the ICP barrel is unaffected by the SICM barrel potential; whereas
      for ion channels that are gated by charged ligands, enhanced channel activity can
      be obtained by biasing the SICM barrel at potentials with opposite polarity to
      the charge of the ligand molecules. Finally, a proof-of-principle experiment is
      performed and site-specific molecular/ionic flux sensing is demonstrated at
      single-ion-channel level, which show that the MP-ICP platform can be used to
      quantify local molecular/ionic concentrations.

PMID- 29226634
TI  - Post-intervention sustainability of a brief psycho-educational support group
      intervention for family caregivers of cancer patients.
AB  - INTRODUCTION: Family caregivers of cancer patients experience many negative
      effects due to the heavy responsibility involved. Although various psychosocial
      interventions have been found to improve caregivers' quality of life (QOL), the
      sustainability of the benefits of these interventions over time has been less
      consistently investigated and hence less clearly established. Extending previous
      research on the immediate post-intervention effects, this study aims to examine
      the trajectories of change in caregivers QOL over an 8-week follow-up period.
      METHODS: Caregivers of patients attending an outpatient clinic at a cancer center
      in Singapore were recruited. Participants had to fulfill the following criteria:
      (a) between 21 and 74 years; (b) willing to attend hour-long weekly programs for
      4 weeks; (c) able to understand, speak, and read English; (d) a family member
      living with and providing care and support for the patient; and (e) provide
      written informed consent. Participants completed the Caregiver QOL-Cancer scale
      at baseline, immediately post-intervention, and at 4 and 8 weeks after the end of
      the intervention. Data from 56 participants were analyzed. RESULTS: Majority of
      participants exhibited a stable trajectory of change in their QOL, while a small
      number of participants either improved or declined. DISCUSSION: Understanding the
      sustainability of the effects of the intervention is important in determining the
      need to initiate periodic "booster" sessions to provide consistent support for
      caregivers. Further research could investigate the sustainability over an even
      longer period, as well as intra-individual change trajectories using growth
      modeling among a larger sample.

PMID- 29226635
TI  - Diagnostic Value of Serum Procalcitonin in Early Infection after Internal
      Fixation for Traumatic Fracture.
AB  - BACKGROUND: This study aimed to observe the changes of serum procalcitonin (PCT)
      and C-reactive protein (CRP) concentrations after internal fixation for traumatic
      fracture and to discuss the diagnostic value of these two indicators in early
      infection after internal fixation for traumatic fracture. METHODS: Patients who
      received internal fixation for traumatic fracture at our hospital from June 2014
      to December 2016 were included. They were divided into infection group (12 cases)
      and non-infection group (166 cases), depending on whether infection occurred.
      Venous blood samples were collected from cases in both groups on day 1, day 4,
      and day 9 after surgery. Changes in PCT and CRP levels were detected at different
      time points. RESULTS: As compared with the non-infection group, PCT and CRP
      levels were significantly increased at each time point after surgery in the
      infection group. The sensitivity of PCT combined with CRP in the detection of
      early infection after surgery was higher than that of either used alone.
      CONCLUSIONS: The serum PCT level can be used as an early diagnostic indicator of
      infection after internal fixation for traumatic fracture. The combined use of PCR
      and CRP levels can increase the sensitivity of detection.

PMID- 29226636
TI  - The Value of GPC3 and GP73 in Clinical Diagnosis of Hepatocellular Carcinoma.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased over
      the past decades in China. Current screening methods of HCC such as detection of
      alpha-fetoprotein (AFP) combined with liver ultrasonography remain
      unsatisfactory. Many HCC patients have already missed the optimal treatment
      period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3)
      and Golgi protein 73 (GP73) in the detection of HCC. METHODS: Thirty-nine
      patients with HCC and 31 patients with liver cirrhosis were enrolled. The level
      of serum GPC3 and GP73 were determined by ELISA. The expression of GPC3 mRNA and
      GP73 mRNA in peripheral blood mononuclear cell (PBMC) and liver tissues were also
      measured with qRT-PCR. Then, receiving operating characteristic (ROC) curves were
      plotted to detect the sensitivity and specificity of serum GPC3 and GP73 in the
      diagnosis of HCC. RESULTS: The levels of serum GPC3 and GP73 in the HCC group
      were significantly higher than in the cirrhosis group (p < 0.0001). Patients with
      GPC3 > 9.3 MUg/L and GP73 > 77.68 ng/mL had a risk of HCC of 92.31%. The HCC
      diagnosis ROC curve analysis indicated that when setting the GPC3 cutoff value >
      9.3 MUg/L, AUC = 0.956. The sensitivity and specificity of GPC3 were 89.74% and
      96.77%, respectively, with a positive predictive value of 97.2%, negative
      predictive value of 88.2%, + LR of 27.82 and - LR of 0.11. When setting GP73
      cutoff value > 77.68 ng/mL, AUC = 0.937. The sensitivity and specificity of GP73
      were 92.31% and 83.87%, respectively, with positive predictive value of 87.8%,
      negative predictive value of 89.7%, + LR of 5.72 and - LR of 0.092. No
      significant difference (p > 0.05) was found between GPC3 and GP73 AUC in ROC
      curves, indicating that these two biomarkers were equivalent in the prediction of
      HCC. CONCLUSIONS: The expression of serum GPC3 and GP73 was significantly higher
      in the HCC patients compared with the cirrhosis patients. GPC3 and GP73 might be
      effective non-invasive diagnostic indicators of HCC.

PMID- 29226637
TI  - The Value of Mean Platelet Volume for Prognosis of Patients with Acute Cerebral
      Infarction.
AB  - BACKGROUND: The purpose of this study was to investigate the value of mean
      platelet volume (MPV) for prognosis of patients with acute cerebral infarction
      (ACI). METHODS: One hundred ACI patients and 80 healthy volunteers acting as
      healthy controls (HCs) were consecutively included in this study. Their baseline
      clinical and laboratory characteristics were extracted from an electroniccase
      system. ACI patients were followed for 90 days to collect the main study
      endpoints including poor prognosis, death due to cardiovascular causes, and the
      recurrence of stroke. ACI patients were evaluated after 7 days in the hospital
      using the National Institute of Health Stroke Scale (NIHSS) score to evaluate
      stroke severity on admission and using the modified Rankin Scale (mRS) to
      evaluate functional disorders. Receiver operating characteristic (ROC) curve
      analysis was used to estimate the predictive value of MPV on ACI. Kaplan-Meier
      survival analysis and Cox regression models were used to analyse the value of MPV
      as a predictor of ACI. RESULTS: This study suggested that MPV and rate of
      hypertension were higher in ACI patients than in the HC group. In the follow-up
      period, 32 ACI patients suffered study endpoints; they had higher average MPV,
      NIHSS scores, longer ACI onset times, and shorter event-free survival time
      compared to control patients. ROC curves showed that MPV was an index for
      prognosis of ACI patients with an AUC of MPV of 0.82 (95% confidence interval
      (CI): 0.74 - 0.90), and the best cutoff was 10.05 fL. MPV, NHISS scores, age, and
      TG were independent risk factors for endpoints of ACI patients. MPV with hazard
      ratio (HR) was 1.94 (95% CI, 1.37 - 2.72, p = 0.000), NIHSS score with HR was
      1.22 (95% CI, 1.03 - 1.44, p = 0.021), age with HR was 1.06 (95% CI, 1.00 - 1.11,
      p = 0.038), and TG HR was 0.60 (95% CI, 0.36 - 1.00, p = 0.048) using Cox
      regression models. P ? 0.05 for all groups was considered statistically
      significant. CONCLUSIONS: Mean platelet volume was an independent risk factor and
      serves as a sensitive index for the prognosis of ACI patients.

PMID- 29226638
TI  - Reference Values of Certain Serum Indicators of Liver Fibrosis.
AB  - BACKGROUND: Liver fibrosis shows a continuously increasing trend worldwide, due
      to alcohol abuse, obesity, and, to a lesser extent, chronic hepatitis B and C.
      Biopsy is still considered the "gold standard" for diagnosis of liver fibrosis.
      However, it has a number of limitations, such as invasiveness, high cost, need
      for specialists to conduct and interpret biopsy results, risk of complications,
      inability to dynamically monitor the pathological process, low patient
      compliance, and uneven fibrosis distribution. Therefore, there is an increasing
      demand for non-invasive serum markers that are characterized by easy
      implementation, low cost, possible repeatability, and high patient compliance.
      METHODS: For a period of two years, 82 clinically healthy, middle aged subjects,
      mean age 40.5 +/- 12.37 years, range 21 - 67 years, were studied. The group was
      tested for platelet count, prothrombin time, and the following biochemical
      parameters: Cholesterol - total, HDL, LDL; AST; ALT; GGT; total bilirubin, alfa-2
      macroglobulin; haptoglobin and ELF (Enhanced Liver Fibrosis). RESULTS: Reference
      values of a large number of serum indicators of liver fibrosis are disputable and
      unspecified. A direct proportional and moderate correlation was found between the
      BMI and AST, ALT, INR, APRI, GPRI, and Forns Index. CONCLUSIONS: We present our
      original reference values for ELF, AST/ALT, ARPI, GRPI, Fib 4, and Forns Index in
      82 clinically healthy subjects.

PMID- 29226639
TI  - Early Diagnosis of Oral Squamous Cell Carcinoma by Salivary microRNAs.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC), the most common type of oral
      cancer, and represents more than 90% of malignancies of the oral cavity.
      Worldwide, each year about 275,000 are newly diagnosed. If detected at an early
      stage, OSCC has a survival rate of up to 80% compared to the detection in later
      stages (T3-T4) when a survival rate of 20 - 30% is present. METHODS: Because OSCC
      presents these survival rates, there is an urgent need to introduce new non
      invasive molecular biomarkers for the early detection of OSCC from saliva, which
      will contribute to an increased long term survival rate for these patients.
      RESULTS: MicroRNAs represent small, non-coding RNAs that have important roles in
      biochemical mechanisms, carcinogenesis, cell proliferation, embryogenesis, and
      other mechanisms involved at the molecular level in the functioning of the human
      body. CONCLUSIONS: In the last decade, due to the fact that forensic genetics
      developed significantly, salivary microRNAs were increasingly studied as non
      invasive molecular biomarkers which could aid in early diagnosis, monitoring, and
      prognosis of oral cancers. This review will present the most important salivary
      microRNAs which are involved in oral carcinogenesis, especially those which could
      be used as potential biomarkers in early detection, monitoring, and prognosis of
      oral cancers by non-invasive techniques.

PMID- 29226640
TI  - Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the
      Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have significantly increased
      cardiovascular (CV) morbidity and mortality that are not accounted for by
      traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have
      been shown to be involved in the pathogenesis of CV diseases. Objective: This
      study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D
      concentrations in RA patients, and to determine their association with CV risk in
      RA. METHODS: Serum samples from 46 RA patients and 45 healthy controls were
      tested for PON1 R192Q genotypes and serum vitamin D concentrations. The
      cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels,
      traditional CV risk factors, medication use, and RA disease activity status were
      also assessed. RESULTS: PON1 polymorphism and low serum 25-hydroxyvitamin D were
      significantly associated with increased CV risk (p < 0.05). Compared to patients
      with either the PON1 QQ genotype or the QR genotype, patients with the RR
      genotype demonstrated decreased CV risk on multivariate analysis, controlling for
      traditional CV risk factors, C-reactive protein levels, prednisone use, and
      cholesterol-lowering medication use (p < 0.05). CONCLUSIONS: There was a
      relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25
      hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1
      genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA
      patients.

PMID- 29226641
TI  - Modified Complete Blood Count Indices as Predicting Markers of Preeclampsia from
      Gestational Hypertension: Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte
      Ratio, and.
AB  - BACKGROUND: To evaluate modified complete blood count (CBC) indices as a
      predicting marker of preeclampsia (PE) from gestational hypertension (GH), we
      analyzed the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio
      (PLR), and platelet to neutrophil ratio (PNR). PNR was a newly designed index in
      this study based on results of PE patients having a tendency toward higher
      neutrophil count and lower platelet count compared to normal pregnant women in
      previous studies. METHODS: We recruited 86 normal pregnant women, 33 patients
      with GH and 68 patients with PE. Subjects with any history of membrane rupture,
      infection, or multiple pregnancies were excluded. PNR, NLR, and PLR values
      including other CBC indices were statistically analyzed. RESULTS: NLR value of PE
      patients was significantly higher than GH patients (p = 0.011). PNR value was the
      most statistically significant index separating patients with PE and GH (p <
      0.001). PLR value was lower in patients with PE compared to GH; however,
      statistical significance was low. CONCLUSIONS: NLR as well as PNR is a useful
      index to help predicting progression from GH to PE. Further studies are required
      to evaluate the full extent of utility of PNR as a predictive index in PE
      patients.

PMID- 29226642
TI  - Homoarginine Associates with Zonulin and Tryptophan - Findings in a High-Risk
      Cohort of Patients Carrying an AICD.
AB  - BACKGROUND: Homoarginine (hArg) is known to have an impact on nitric oxide (NO)
      metabolism. It seems to increase NO generation and/or availability, thereby
      enhancing endothelial function. In addition, hArg is connected to energy
      metabolism since the key enzyme, L-arginine-glycine amidinotransferase (AGAT) for
      hArg synthesis in the kidneys, is also involved in the synthesis of energy
      metabolites like guanidinoacetate. Former studies indicate that low levels of
      hArg are linked to cardiovascular disease and increased all-cause mortality.
      METHODS: This study investigated the dependence of plasma hArg on various
      biochemical and clinical factors in 229 patients carrying an automatic,
      implantable cardioverter/defibrillator (AICD) using multiple linear regression
      analysis (Generalized Linear Model, GLM). RESULTS: GLM revealed a highly
      significant, positive association between hArg and zonulin (p < 0.001). hArg was
      also positively correlated with tryptophan (p = 0.004), BMI (p = 0.02), and body
      weight (p = 0.02). Patients with hsCRP above 10 mg/L had significantly lower hArg
      concentrations than patients with hsCRP <= 10 mg/L. CONCLUSIONS: The highly
      significant positive association of hArg with zonulin is a novel finding which
      may indicate a different meaning of circulating versus local (gut) zonulin.
      Therefore, further experimental and clinical investigation is needed to explore
      this association, focusing on possible pathophysiological pathways and the role
      of circulating zonulin levels in cardiovascular disease. The positive correlation
      of hArg and Trp also deserves further research because both amino acids might
      have a protective effect on cardiovascular disease by inhibition of the enzyme
      alkaline phosphatase. Eventually, our study associates low hArg concentrations
      with chronic low-grade inflammation and parameters of malnutrition in
      cardiovascular high-risk patients.

PMID- 29226643
TI  - Prognostic Value of Serum Lactate Dehydrogenase in Patients with Nasopharyngeal
      Carcinoma: a Meta-Analysis.
AB  - BACKGROUND: Serum-lactate dehydrogenase (S-LDH) is reported to be associated with
      poor survival in patients with nasopharyngeal carcinoma (NPC); however, the
      results are inconsistent. The aim of the study was to perform a meta-analysis to
      evaluate the prognostic value of S-LDH in patients with NPC. METHODS: PubMed and
      Web of Science were searched for relevant studies, and the fixed-effects model
      was employed to pool the hazard risks (HRs) from individual studies when no
      substantial heterogeneity was detected; otherwise, the random-effects model was
      used. Heterogeneity and publication bias were also analyzed. RESULTS: A total of
      18 studies involving 13,789 patients were included in the meta-analysis, serum
      LDH level was associated with worse outcome in NPC patients. The combined HR for
      overall survival (OS) was 1.86 (95% confidence interval [CI]: 1.66 - 2.08; p <
      0.01), and the pooled HRs for disease-free survival (DFS), distant metastasisfree
      survival (DMFS), and distant local relapse-free survival (LRFS) were 1.64 (95%
      CI: 1.45 - 1.86), 2.64 (95% CI: 2.15 - 3.25), and 2.59 (95% CI: 1.74 - 3.87),
      respectively. CONCLUSIONS: Our results suggest that higher serum LDH level is
      associated with worse survival in patients with NPC, which is helpful for a
      personalized treatment strategy for NPC patients.

PMID- 29226644
TI  - The Role of MicroRNA-1207-5p in Colorectal Cancer.
AB  - BACKGROUND: MicroRNA-1207-5p (MiR-1207-5p) has been identified as a tumor
      suppressor in many types of cancer. However, less research has been done with
      respect to the role of miR-1207-5p in colorectal cancer (CRC). The aim of our
      study was to analyze the role of miR-1207-5p in CRC. METHODS: Total RNA was
      extracted from clinical specimens and CRC cell line, and the expression of miR
      1207-5p was examined by real-time PCR (q-PCR). The human CRC cell lines were
      transfected with the miR-1207-5p mimic, negative control (NC). Cell Counting Kit
      8 (CCK-8) assays were performed to measure cell viability. The colony formation
      assay was carried out to analyze the clone forming ability. The cell cycle was
      analyzed by flow cytometer. The significance of the data was calculated by the
      SPSS software. RESULTS: The relative expression of miR-1207-5p in CRC tissues and
      adjacent noncancerous tissues (normalized to U6 expression) were 0.0546 +/-
      0.0131 and 0.1928 +/- 0.0317, (p < 0.01), with obvious significant difference
      between the two groups. The expression of miR-1207-5p was significantly lower in
      CRC patients with advanced TNM stage (p = 0.018) and positive lymph node
      metastasis (p = 0.033) and shorter overall survival (p = 0.049). In addition, it
      enhances the expression of miR-1207-5p suppressed cell proliferation ability,
      clone forming ability, and promoted cell apoptosis in vitro. CONCLUSIONS: The
      lower expression of miR-1207-5p was correlated with advanced TNM stage and lymph
      node metastasis and shorter patient overall survival. These results indicated
      that miR-1207-5p may function as tumor suppressor in CRC.

PMID- 29226645
TI  - Thrombophilic Mutations Among Patients with Sickle Cell Disease.
AB  - BACKGROUND: Factor V-Leiden (FVL), Prothrombin (PRT) G20210A, and Methylene
      Tetrahydro Folate Reductase (MTHFR) C677T and A1298C mutations are major
      inherited risk factors of thrombotic complications. Our aim in this study was to
      investigate the prevalence of these mutations among Tunisian sickle cell
      patients. METHODS: Study subjects comprised 64 patients and 100 healthy controls.
      FVL, PRT G20210A, and MTHFR genotypes were determined using a reverse dot blot
      based method. RESULTS: In the patient population studied, the prevalence of FV
      Leiden was not statistically different from controls while a significant
      prevalence of heterozygous PRT G20210A mutation among patients (10.93%) was
      found. An increased frequency of the MTHFR 677 C>T genotype was seen among
      patients as well as controls. The results showed no significant association
      between the MTHFR A1298C mutation and sickle cell disease (SCD). However, the
      prevalence of carrier among studied patients was 15.62% compared to 7% among
      healthy subjects. CONCLUSIONS: In conclusion, our data suggest a significant
      association between PRT G20210A and MTHFR C677T and sickle cell disease among
      Tunisian patients.

PMID- 29226646
TI  - Comparison of Citrate Buffer with Sodium Fluoride as Additives in Determining
      Glycemia.
AB  - BACKGROUND: The objectives of this study are to compare the effect of sodium
      fluoride and citrate on the stability of glucose in samples maintained at room
      temperature up to three hours, and to assess the clinical impact in the
      O'Sullivan test results after changing the additives in the collecting tubes.
      METHODS: The selected population was pregnant women between the 24th and 28th
      week of gestation, who were at the health center to undergo the O'Sullivan test
      as part of the screening program for GDM (gestacional diabetes mellitus). Two
      blood samples were extracted from each patient: one using a tube with citrate and
      sodium fluoride buffer (tubes Vacuette Glucomedics citrate, 2 mL, Ref 454347)
      (tube C) and another containing just sodium fluoride (BD Vacationer tubes FX
      fluoride, 2 mL, Ref 368920) (tube F). The statistical treatment of the data was
      performed using SPSS version 24 and Method validator. Finally, we assessed the
      real clinical impact of replacing tubes C for tubes F in the classification of
      pregnant women. To do so, we collected the results of O'Sullivan tests conducted
      in our hospital during a year, all of them done in tubes F, and we applied the
      mean difference calculated in T = 1 to estimate the number of pregnant women that
      should be reclassified. RESULTS: The average glycaemia in tubes C are
      significantly greater than average glycaemia in tubes F (p < 0.05) at all time
      points. The clinical impact assessment was done over the 6,526 O'Sullivan test
      results with a prevalence of positive tests of 21.35%. The prevalence using tubes
      C instead of tubes F estimated with mean differences previously calculated is
      33.45%. CONCLUSIONS: The glucose concentrations in tubes F stored at room
      temperature up to 3 hours were significantly lower (p < 0.05) than those measured
      in tubes C stored under the same conditions. We observed that it is in the first
      minutes after extraction, while the samples are collected and aliquots done, that
      the glucose consumption occurs in tubes F, but not in tubes C. There is a need to
      change the preanalytical conditions to prevent any loss of glucose. This will
      enable more accurate diagnosis and management of diabetes mellitus.

PMID- 29226647
TI  - Human Peripheral Blood Cells mRNA Levels are Highly Sensitive to Duration of Ex
      Vivo Post-Sampling Conditions Prior to RNA Isolation.
AB  - BACKGROUND: This study aimed to evaluate an effect of the time period between
      drawing the peripheral blood and specimen processing on the stability of mRNA
      levels of 7 selected genes. METHODS: Blood samples derived from 15 healthy
      volunteers were always processed at five consecutive time points 0.5, 1.5, 2, 3,
      and 9 hours; mRNA was quantified by real-time PCR. RESULTS: Anti-inflammatory
      genes CCL2 and IL10 showed a significant rise of expression between the 3rd and
      9th hour after blood collection (p <= 0.5). Significant decrease of mRNA levels
      in relation to time lag was observed for TLR4 and MYC genes (p <= 0.5).
      Interestingly, the initial two hours after drawing the blood revealed a high
      interindividual variability in cellular response to stress connected with blood
      drawing and ex vivo post-sampling condition. CONCLUSIONS: These results point out
      the need for a strict standardization of handling the blood specimen with regards
      to peripheral blood sample processing time between phlebotomy and RNA isolation.

PMID- 29226648
TI  - Fibulin Levels in Autosomal Dominant Polycystic Kidney Disease and Its
      Relationship to Arterial Stiffness.
AB  - BACKGROUND: The objective of the present study was to evaluate fibulin 1 levels
      in different stages of patients with autosomal dominant polycystic kidney disease
      (ADPKD) and investigate possible connections between fibulin-1 and arterial
      stiffness. METHODS: For this cross-sectional study, we included 74 patients with
      ADPKD (mean age, 50.92 +/- 15.70 years) and 32 healthy controls (mean age, 49.53
      +/- 7.32 years). Patients with ADPKD were classified based on CKD epidemiology
      collaboration (CKD-EPI) equation assessments of estimated glomerular filtration
      rate (eGFR). Blood levels of fibulin 1 and creatinine levels were analyzed. We
      measured brachial artery PWV (baPWV), augmentation index (AIx), and pulse
      pressure (PP) for the assessment of arterial stiffness and systolic and diastolic
      blood pressures (SBP and DBP, respectively). RESULTS: Fibulin 1 was significantly
      higher in the patient group (p < 0.001). SBP, DBP, MAP, PP, and baPWV levels were
      also significantly higher in the patient group. A statistically significant
      positive correlation was found between fibulin 1 and creatinine (r = 0.377, p =
      0.001). No significant correlation was found between the fibulin 1 levels and
      age, SBP, DBP, MAP, baPWV, and AIx. CONCLUSIONS: Plasma concentrations of fibulin
      1 increased in patients with ADPKD. Arterial stiffness measured by baPWV
      increased in patients with ADPKD, but it was not related to fibulin 1 levels.

PMID- 29226649
TI  - Comparison of the Diagnostic Power of Serum IL-6, IL-8 and TNF-alpha for the
      Idiopathic Anterior Uveitis in Children.
AB  - BACKGROUND: Uveitis is the inflammation of the uvea that often occurs in
      children. There are many causes of disease, but some of them do not have any
      reasons and are then called idiopathic uveitis. Cytokines play an important role
      in the regulation of the immune response. Determination of cytokine profiles
      could contribute to the explanation of the etiology of uveitis and could serve to
      evaluate the inflammation intensity as well as be helpful in the early diagnosis
      this disease. The purpose of this study was to determine the serum level of
      selected inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-8 (IL
      8), and tumor necrosis factor alpha (TNF-alpha) and to compare their diagnostic
      power as a markers of idiopathic anterior uveitis in children. METHODS: The study
      was carried out on 28 children diagnosed with idiopathic anterior uveitis. The
      reference group comprised 30 healthy children. Serum IL-6, IL-8, and TNF-alpha
      concentrations were measured with specific enzyme-linked immunoassay (ELISA)
      methods. RESULTS: The mean values of IL-6, IL-8, and TNF-alpha in the children
      with idiopathic anterior uveitis were significantly higher than those found in
      the reference group. The highest sensitivity, specificity, accuracy, positive and
      negative predictive value, and likelihood ratio of a positive test result were
      achieved for IL-8. There was a significant difference between the area under the
      curve for IL-6 and IL-8. CONCLUSIONS: Increased serum concentrations of
      interleukin IL-6, IL-8, and TNF-alpha may suggest that these cytokines induce
      inflammatory changes in the ocular surface. Analysis of cytokine levels showed
      that IL-8 has the highest diagnostic power and is the best marker for diagnosis
      of idiopathic anterior uveitis in children.

PMID- 29226650
TI  - Multiple Nonleukemic Myeloid Sarcoma Associated Hemophagocytic
      Lymphohistiocytosis in an Adult.
AB  - BACKGROUND: Nonleukemic myeloid sarcoma (MS) occurs rarely. Hemophagocytic
      lymphohistiocytosis (HLH) is a rare and potentially fatal condition. We report a
      rare case of nonleukemic MS associated with HLH. METHODS: Hematologic
      investigation, 18F-FDG PET/CT, bone marrow aspirate and biopsy, and lymph node
      biopsy were performed in a 25-year-old male patient. RESULTS: The patient was
      given a short-term treatment of etoposide and dexamethasone to control HLH. Then
      he received chemotherapy and responded well. CONCLUSIONS: It is important to find
      the underlying cause of HLH in high-risk patients. HLH can occur secondary to
      nonleukemic MS. Early diagnosis and treatment can improve survival.

PMID- 29226651
TI  - Quantitative Distinction of Morphological Characteristics of White Blood Cells in
      Peripheral Blood Through Texture Analysis Using Gray Level Co-Occurrence Matrix.
AB  - BACKGROUND: Texture features are valuable clues for skilled technicians to
      differentiate peripheral blood (PB) white blood cells (WBCs). Some studies have
      tried to distinguish WBCs automatically by using texture analysis. However, no
      study so far has applied a gray level co-occurrence matrix (GLCM) to images of PB
      WBCs. Here, we developed a new GLCM method, called the CM-Tx method, for
      automatically distinguishing PB WBCs. METHODS: We used a total of 199 images of
      six different types of PB WBCs, taken from PB smears of 12 healthy volunteers, as
      objective standard images for the analysis. The six types were band form
      neutrophil, segmented form neutrophil, eosinophil, basophil, lymphocyte, and
      monocyte. Using in-house FORTRAN programs, three types of GLCM (R: distance (d) =
      1, direction (theta) = 0 degrees ), (U: d = 1, theta = 270 degrees ) and (AE: d =
      1, theta = 15 degrees  x q: q = 0, ..., 23), the mean intensity (MI) of each
      image and nine different texture distinction indexes (TDIs) for each GLCM were
      calculated. Then, a threshold value (TV) for distinguishing the type of PB WBC
      was selected from the dot plots of all TDIs and the MI. RESULTS: In total, we
      made 1,194 GLCMs. Using the selected TVs of the TDI, four sequential binary
      divisions could distinguish five types of PB WBCs. First, monocytes were
      distinguished (sensitivity 100%, specificity 100%, p < 0.0001) with the TV of the
      inverse difference moment of the GLCM (U). Then, segmented and band form
      neutrophils were distinguished from the remaining (100%, 99%, p < 0.0001) with
      the TV of the contrast of the GLCM (AE). Next, lymphocytes were distinguished
      (100%, 98%, p < 0.0001) with the TV of the entropy of the GLCM (AE). Finally,
      basophils were distinguished (82.4%, 100%, p < 0.0001) from eosinophils with the
      TV of the summed entropy of the GLCM (R). Band form neutrophils could not be
      distinguished from segmented form neutrophils. The average sensitivity of the CM
      Tx method for the five types was 95.6%, and its average specificity was 99.3%.
      CONCLUSIONS: The CM-Tx method can distinguish five types of PB WBCs by using
      numerical differences only in texture futures quantified with GLCM. However, some
      other method was needed to distinguish the band and segmented form neutrophils
      from each other.

PMID- 29226652
TI  - A Pooled Analysis of The Clinical Utilities of Long Non-Coding RNA Based
      Molecular Signature for Diffuse Large B Cell Lymphoma.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have been highlighted as promising
      biomarkers for several types of malignancies. The current meta-analysis sought to
      investigate the clinical value of lncRNA-based molecular signatures as biomarkers
      for diagnosis, subtype classification, and prognosis in diffuse large B cell
      lymphoma (DLBCL). METHODS: A systematic search of the online databases was
      carried out and data were retrieved by pairs of independent reviewers. Effect
      sizes of the diagnostic parameters were combined using a quantitative meta
      analysis. In the prognostic analysis, hazard ratio (HR) with 95% confidence
      interval (CI) for the primary endpoints of overall survival (OS) and progression
      free survival (PFS) were meta-analyzed. RESULTS: Our data exhibited that lncRNA
      expression profiling harvested a pooled sensitivity of 0.87 (95% CI: 0.78 -
      0.92), specificity of 0.84 (95% CI: 0.75 - 0.90), and AUC of 0.92 in
      distinguishing DLBCL cases from cancer-free participants. For subtype
      classification, lncRNA signature could discriminate germinal center B-cell-like
      (GCB) and activated B-cell-like (ABC) DLBCL cases with an estimated sensitivity
      of 0.92 (95% CI: 0.89 - 0.95), specificity of 0.89 (95% CI: 0.83 - 0.93) and AUC
      of 0.96. Prognostic analysis manifested that altered lncRNA profiles predicted
      unfavorable clinical outcomes of DLBCL in OS (univariate analysis: HR = 1.45, 95%
      CI: 1.14 - 1.83, p < 0.001). Further subgroup study stratified by
      clinicopathological features revealed that the LDH level, IPI score, subtype, and
      testing pattern of lncRNAs were markedly correlated with the OS in DLBCL.
      CONCLUSIONS: Collectively, our data uncover that lncRNA expression profiling
      retains a relatively high accuracy in the diagnosis and classification of DLBCL.
      Altered levels of lncRNAs are also closely associated with worse OS and appeared
      to be powerful predictors in forecasting prognosis in DLBCL.

PMID- 29226653
TI  - A Preliminary Study of the Value of Plasma microRNA-193b and Soluble Urokinase
      Type Plasminogen Activator Receptor in Identifying Patients with Early-Stage
      Colorectal Cancer and.
AB  - BACKGROUND: Early detection and management of colorectal cancer (CRC) and
      colorectal adenoma (CRA) reduces the mortality and morbidity of CRC, but there is
      a lack of ideal circulation biomarkers. METHODS: A total of 80 patients with
      early-stage CRC and CRA and 30 healthy controls were included in this preliminary
      study. Plasma samples were collected before colonoscopy and prepared for
      measurement of microRNA193b and soluble uPAR. RESULTS: Plasma level of miR-193b
      was decreased through the normal-adenoma-carcinoma sequence with no significant
      difference between patients with CRC and advanced CRA. The AUC of ROC curve
      evaluating the value of miR-193b in discriminating patients with early stage CRC
      or advanced CRA from patients with non-advanced CRA or normal control subjects
      was 0.849 (95% CI 0.773 - 0.923, p < 0.001). Significant alteration of plasma
      suPAR is only observed in CRC group (p < 0.001). CONCLUSIONS: Plasma miR-193b may
      be a novel candidate biomarker for screening patients with early-stage CRC and
      advanced CRA.

PMID- 29226654
TI  - Evaluation of Hepcidin and Atherosclerosis in Dialysis Patients.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a condition that involves 10% - 15%
      of population worldwide, which increases the risk of cardio-vascular diseases
      (CVD). Chronic kidney disease is one of the main reasons for illness and
      mortality in the world. Chronic kidney disease is a serious health problem caused
      by involvement of a large number of patients with kidney injury, especially in
      industrial countries. Among the main reasons for this are population living
      longer and the number of diseases in elderly persons, such as diabetes mellitus
      type 2, hypertension, and cardio-vascular diseases. METHODS: We evaluated 63
      patients on chronic dialysis at the Dialysis Centre at University
      "Aleksandrovska" Hospital; the average age was 49.9 +/- 7.8. Their results were
      compared to 63 age matched controls. Blood samplings were taken before dialysis
      procedure. In the included groups, we measured CBC, serum iron (by Ferrozine
      method), ferritin, soluble transferrin receptors and hsCRP (by nephelometric
      method), hepcidin (by ELISA method), and homocysteine (by CLIA method). IMT was
      measured by using electronic calipers and evaluated by automated software
      programs. RESULTS: We established elevated serum hepcidin levels in CKD patients
      (205.1 +/- 29.9 ug/L) compared to the control group (20.8 +/- 3.1 ug/L), p <
      0.001. Serum homocysteine and hsCRP concentrations were elevated in CKD cases
      (48.7 +/- 6.8 umol/L; 29.7 +/- 4.1 mg/L) compared to controls (7.9 +/- 1.8
      umol/L; 1.1 +/- 0.4 mg/L), p < 0.005. In patients with CKD we found a strong
      positive correlation between serum hepcidin and homocysteine concentrations, r =
      0.879, p < 0.001. In patients with impaired kidney function soluble transferrin
      receptors correlated negatively to hepcidin: r = -0.799, p < 0.001. In dialysis,
      the transferrin concentration correlated highly positive to hepcidin: r = 0.691,
      p < 0.001. IMT in CKD patients correlated positively to hepcidin and homocysteine
      levels: r = 0.788 and r = 0.841, respectively, p < 0.005. CONCLUSIONS: Chronic
      kidney disease is connected to cardio-vascular disease risk factors. CKD might be
      an independent CVD risk factor. In early kidney injury stages, increased
      morbidity is found from CVD. The risk of fatal and non-fatal cardio-vascular
      incidents is connected to kidney injury. For clinical practice, early evaluation
      of hepcidin and atherosclerosis in chronic kidney disease patients is very
      important.

PMID- 29226655
TI  - Increased Expression of PCNA-AS1 in Colorectal Cancer and its Clinical
      Association.
AB  - BACKGROUND: The aim is to study the expression of PCNA-AS1 in colorectal cancer
      (CRC) tissue and paired-adjacent normal tissue and the relationship between its
      expression level and clinical pathological features. METHODS: Using real-time
      qPCR, PCNA-AS1 expression levels were detected in 114 cases to establish the
      relationship between its expression and clinicopathologic features. Moreover, the
      expressions of PCNA-AS1 were investigated in CRC and normal colonic epithelial
      cell lines. RESULTS: PCNA-AS1 was upregulated in CRC patients. The difference was
      statistically significant (p < 0.001). The expression level was significantly
      correlated with the tumor invasion and TNM stage. The area under the receiver
      operating characteristic curve, sensitivity, and specificity were 0.824, 0.632,
      and 0.860, respectively. Moreover, PCNA-AS1 was up-regulated in CRC cell lines.
      CONCLUSIONS: PCNA-AS1 may function as a potential tumor biomarker for diagnosing
      CRC.

PMID- 29226656
TI  - Peripheral Blood miR-181-5p Serves as a Marker for Screening Patients with
      Osteoarthritis by Targeting TNFalpha.
AB  - BACKGROUND: Increasing evidence has suggested the important role of miRNAs in the
      progression of osteoarthritis (OA). In the current study, we explored the role of
      miR-181-5p in the peripheral blood and bone tissues of OA patients for the first
      time. METHODS: The level of miR-181-5p was evaluated in the peripheral blood and
      cartilage of OA patients using real time PCR analysis. ROC analysis was performed
      to explore whether peripheral blood and cartilage miR-181-5p could screen OA
      patients from normal controls. Western blot assay and dual luciferase reporter
      assay were carried out to validate the possible target gene of miR-181-5p in
      SW1353 cells. RESULTS: For the first time, we confirmed that the expression of
      miR-181-5p was significantly reduced in the peripheral blood and cartilage of OA
      patients, suggesting that miR-181-5p may be involved in the process of cartilage
      injury in OA degradation. Furthermore, ROC analysis showed that both peripheral
      blood and cartilage miR181-5p could screen OA patients from healthy controls.
      Moreover, we found that overexpression of miR-181-5p significantly suppressed the
      expression of TNFalpha, while inhibition of miR-181-5p enhanced the level of
      TNFalpha. Bioinformatic predictions identified a conserved binding site in the
      3'UTR of TNFalpha by miR-181-5p. In addition, dual luciferase reporter assay
      indicated that miR-181-5p markedly suppressed the relative luciferase activity of
      TNFalpha. These data indicated that TNFalpha was a target gene of miR-181-5p.
      CONCLUSIONS: In summary, reduced miR-181-5p expression in the peripheral blood
      and cartilage tissues may serve as a potential biomarker to screen OA patients
      from healthy controls mainly by targeting TNFalpha.

PMID- 29226657
TI  - Short Centrifugation to Ameliorate Turn-Around-Time in Routine Coagulation
      Testing.
AB  - BACKGROUND: Fast and timely analysis of coagulation parameters is mandatory in
      hospital laboratories as the results are decisive for diagnosis and treatment in
      emergency patients. An important factor in TAT (turn-around time) prolongation is
      centrifugation of all samples prior to analysis. According to literature and most
      current SOPs (standard operation protocols) centrifugation time is given with 10
      minutes at approximately 2,000 g and cannot be reduced without infringement of
      standards. Thus, we have attempted to minimize TAT by comparing coagulation test
      results achieved with 5 minutes centrifugation time vs. 10 minutes. If feasible,
      a shorter centrifugation time will result in further optimized TAT and therefore
      save critical time to treatment in emergency patients. METHODS: 96 routine
      clinical samples were tested for prothrombin time ("Quick"), activated partial
      prothrombin time (aPTT), thrombin time, fibrinogen, antithrombin III, and D-Dimer
      with 5 and 10 minutes centrifugation. 405 double measurements were performed.
      RESULTS: Correlation of results were for all 6 parameters ? 0.99. Deviation of
      the mean was lower than 3% for each parameter. 98.5% of results deviated less
      than 10%. Although the analysis results for prothrombin time and for antithrombin
      III show a formal significant difference via Student's t-test, clinically, a
      difference is not evident. CONCLUSIONS: Shortening of centrifugation time for
      coagulation testing seems to have no detrimental effects on the analysis results,
      and might be sought for routine coagulation testing to achieve shorter turn
      around time.

PMID- 29226658
TI  - Application of Commutable ERM-DA474/IFCC for Harmonization of C-reactive Protein
      Measurement Using Five Analytical Assays.
AB  - BACKGROUND: ERM-DA474/IFCC has been used as a reference material for C-reactive
      protein (CRP) since 2012. However, the commutabilities and the capacity for
      harmonizing CRP results of the material and its dilutions have not yet been
      reported. In this study, we aimed to evaluate the harmonization of CRP results
      using commutable ERM-DA474/IFCC. METHODS: Twenty-one serum samples were collected
      and split into five vials. The samples were then analyzed using five popular
      assays (Siemens BN II, Beckman Immage 800, Roche, Diasys, and Leadman). ERM
      DA474/IFCC and four dilutions of healthy human serum containing low levels of CRP
      were also analyzed using the five assays described above. Commutability was
      assessed using the Roche, Diasys, and Leadman assays. Clinical sample results
      from assays were recalibrated based on ERM-DA474/IFCC and its dilutions. RESULTS:
      There were significant variations among the five assays for CRP measurement. The
      slopes ranged from 0.60 to 1.60, and the BN II and Leadman assays showed
      significant negative and positive systemic biases, respectively. ERM-DA474/IFCC
      and its dilutions exhibited commutability among the three assays. After
      recalibration, the slope was reduced to 0.76 - 1.27. CONCLUSIONS: Harmonization
      was not ideal for CRP measurement. ERM-DA474/IFCC may play a role in improving
      harmonization for CRP measurement.

PMID- 29226659
TI  - Performance Evaluation of the Bio-Rad D-100 System for Hemoglobin A1c Assay.

PMID- 29226660
TI  - Bone and Joint Diseases in Present and Future.
AB  - With the increase of elderly population, orthopaedic surgeons need to deal with
      the diseases relatedto aging, such as joint disorders and fragility fractures.
      The number of total joint replacements, forexample, is two times more than it was
      10 years ago. With these backgrounds, the JapaneseOrthopaedic Association (JOA)
      has proposed the concept of locomotive syndrome; conditions underwhich the
      elderly have been receiving care services due to problems of the locomotive
      organs. Toprevent geriatric or disuse syndrome, JOA is currently providing the
      care-prevention programs suchas the loco-check and loco-training. Recent advances
      in the orthopaedic fields were cited in this review article, including the topics
      ofnew biomaterials, regenerative medicine of cartilage, spinal cord injury and
      computer assistedorthopaedic surgery. These new technologies and knowledge are
      changing or have potential to changethe future orthopedic medical care.

PMID- 29226661
TI  - Completely Responsive Multiple Liver Recurrence of Colon Cancer Treated Using
      Chemotherapy with Oral S-1 and Oxaliplatin Plus Bevacizumab : A Case Report.
AB  - Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev)
      is safe andfeasible for patients with advanced or recurrent colorectal cancer, it
      is difficult to achieve a completeresponse (CR) using only chemotherapy. A 67
      year-old man underwent endoscopic mucosal resectionand additional sigmoidectomy
      (D2 dissection) for submucosal invasive sigmoid colon cancer. Multipleliver
      metastases were diagnosed 1.5 years later, and chemotherapy with SOX + bev was
      initiated.Computed tomography (CT) after the end of the third course revealed
      reduced liver recurrence. Livermetastases could not be identified using CT after
      the end of the sixth course. Grade 1peripheralneuropathy was the only side effect
      of this regimen. Subsequently, the chemotherapy regimen waschanged to oral S-1.
      CT evaluation revealed that there was no recurrence at 6 months after theregimen
      change.

PMID- 29226662
TI  - New Approach to Diagnosis and Treatment of Esophageal Motility Disorders by High
      Resolution manometry.
AB  - Esophageal motility disorders (EMD) is characterized by impaired coordinated
      esophageal motilityfunction with symptoms including dysphasia, heartburn or
      noncardiac chest pain. Since EMDs isfunctional disorders, it is usually difficult
      to make a diagnosis by conventional examinations includingendoscopy and
      esophagography. Recently developed high-resolution manometry allows us to
      evaluateesophageal motility function precisely and to make a differential
      diagnosis of EMDs, together withChicago Classification (CC) version 3.0 (CC
      ver3.0). In this article, we reviewed diagnosis of EMDsbased on CC ver3.0 and
      current treatment strategy for EMDs.

PMID- 29226663
TI  - Inquiries About Biomarkers of Acute Liver Failure in Patients Who Underwent
      Living Donor Liver Transplantation Using a Protein Chip Array.
AB  - The causative agent of hepatic encephalopathy (HE) has not been identified with
      certainty. Therecovery of consciousness in patients with acute liver failure
      (ALF) who underwent livertransplantation (LT) is sometimes drastic ; therefore,
      we thought that the causative agents of HEwould change markedly peri-operatively
      in these patients. We examined the biomarkers includingnew agents in the serum of
      patients using the ProteinChip(r) System 4000 (Ciphergen Biosystems,Yokohama,
      JAPAN). Sixteen samples were obtained from four patients with ALF who underwent
      living donor LT(LDLT) at four time points ; pre-operative, one post-operative day
      (1POD), 3POD, and 7POD. We usedthree chips made by the Biomek2000 robot. All
      duplicated samples were assayed and analyzed usingthe CiphergenExpressTM data
      manager. We divided the peri-operative changes in the intensity ofidentified
      peaks into seven patterns. The number of peaks whose intensity shows significant
      changesperi-operatively reached 755. Of course, it is difficult to determine each
      structure in all 755 peaks ; therefore, we should narrowdown the candidates for
      causative agents of HE in further studies. Our own results suggest that
      manydifficulties lie ahead in determining the causative agent of HE.

PMID- 29226664
TI  - Case of a Cardiopulmonary Arrest Due to Postoperative Subglottic Stenosis
      Developed on the Second Day after Lung Surgery.
AB  - We experienced a case of the cardiopulmonary arrest due to subglottic stenosis
      developed on thesecond day after lung cancer surgery. Case : A 73-year-old female
      who was diagnosed with primarylung cancer was referred to our department for
      surgery. The second day after left lungsegmentectomy, she showed respiratory
      discomfort symptoms and exhibited hoarseness and stridor,which were revealed as
      the subglottic stenosis by bronchoscopy. During the emergency airwaymanagement,
      she went into cardiopulmonary arrest. We performed cardiopulmonary
      resuscitationand simultaneous urgent tracheotomy.

PMID- 29226665
TI  - Light-Enhanced Carbon Dioxide Activation and Conversion by Effective Plasmonic
      Coupling Effect of Pt and Au Nanoparticles.
AB  - Photocatalytic reduction of carbon dioxide (CO2) is attractive for the production
      of valuable fuels and mitigating the influence of greenhouse gas emission.
      However, the extreme inertness of CO2 and the sluggish kinetics of photoexcited
      charge carrier transfer process greatly limit the conversion efficiency of CO2
      photoreduction. Herein, we report that the plasmonic coupling effect of Pt and Au
      nanoparticles (NPs) profoundly enhances the efficiency of CO2 reduction through
      dry reforming of methane reaction assisted by light illumination, reducing
      activation energies for CO2 reduction ~30% below thermal activation energies and
      achieving a reaction rate 2.4 times higher than that of the thermocatalytic
      reaction. UV-visible (vis) absorption spectra and wavelength-dependent
      performances show that not only UV but also visible light play important roles in
      promoting CO2 reduction due to effective localized surface plasmon resonance
      (LSPR) coupling between Pt and Au NPs. Finite-difference time-domain simulations
      and in situ diffuse reflectance infrared Fourier transform spectroscopy further
      reveal that effective coupling LSPR effect generates strong local electric fields
      and excites high concentration of hot electrons to activate the reactants and
      intermediate species, reduce the activation energies, and increase the reaction
      rate. This work provides a new pathway toward the efficient plasmon-enhanced
      chemical reactions via reducing the activation energies by utilizing solar
      energy.

PMID- 29226666
TI  - Fluorogenic Detection of Monoamine Neurotransmitters in Live Cells.
AB  - Monoamine neurotransmission is key to neuromodulation, but imaging monoamines in
      live neurons has remained a challenge. Here we show that externally added ortho
      phthalaldehyde (OPA) can permeate live cells and form bright fluorogenic adducts
      with intracellular monoamines (e.g., serotonin, dopamine, and norepinephrine) and
      with L-DOPA, which can be imaged sensitively using conventional single-photon
      excitation in a fluorescence microscope. The peak excitation and emission
      wavelengths (lambdaex = 401 nm and lambdaem = 490 nm for serotonin; lambdaex =
      446 nm and lambdaem = 557 nm for dopamine; and lambdaex = 446 nm and lambdaem =
      544 nm for norepinephrine, respectively) are accessible to most modern confocal
      imaging instruments. The identity of monoamine containing structures (possibly
      neurotransmitter vesicles) in serotonergic RN46A cells is established by quasi
      simultaneous imaging of serotonin using three-photon excitation microscopy. Mass
      spectrometry of cell extracts and of in vitro solutions helps us identify the
      chemical nature of the adducts and establishes the reaction mechanisms. Our
      method has low toxicity, high selectivity, and the ability to directly report the
      location and concentration of monoamines in live cells.

PMID- 29226667
TI  - Enhanced Thermal Conductivity of Graphene Nanoplatelet-Polymer Nanocomposites
      Fabricated via Supercritical Fluid-Assisted in Situ Exfoliation.
AB  - As electronic devices become increasingly miniaturized, their thermal management
      becomes critical. Efficient heat dissipation guarantees their optimal performance
      and service life. Graphene nanoplatelets (GnPs) have excellent thermal properties
      that show promise for use in fabricating commercial polymer nanocomposites with
      high thermal conductivity. Herein, an industrially viable technique for
      manufacturing a new class of lightweight GnP-polymer nanocomposites with high
      thermal conductivity is presented. Using this method, GnP-high-density
      polyethylene (HDPE) nanocomposites with a microcellular structure are fabricated
      by melt mixing, which is followed by supercritical fluid (SCF) treatment and
      injection molding foaming, which adds an extra layer of design flexibility. Thus,
      the microstructure is tailored within the nanocomposites and this improves their
      thermal conductivity. Therefore, the SCF-treated HDPE 17.6 vol % GnP
      microcellular nanocomposites have a solid-phase thermal conductivity of 4.13 +/-
      0.12 W m-1 K-1. This value far exceeds that of their regular injection-molded
      counterparts (2.09 +/- 0.03 W m-1 K-1) and those reported in the literature. This
      dramatic improvement results from in situ GnPs' exfoliation and dispersion, and
      from an elevated level of random orientation and interconnectivity. Thus, this
      technique provides a novel approach to the development of microscopically
      tailored structures for the production of lighter and more thermally conductive
      heat sinks for next generations of miniaturized electronic devices.

PMID- 29226668
TI  - Specific Dopamine Sensing Based on Short-Term Plasticity Behavior of a Whole
      Organic Artificial Synapse.
AB  - In this work, we demonstrate the ultrasensitive and selective detection of
      dopamine by means of a neuro-inspired device platform without the need of a
      specific recognition moiety. The sensor is a whole organic device featuring two
      electrodes made of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate
      PEDOT:PSS-patterned on a polydymethylsiloxane-PDMS-flexible substrate. One
      electrode is pulsed with a train of voltage square waves, to mimic the
      presynaptic neuron behavior, while the other is used to record the displacement
      current, mimicking the postsynaptic neuron. The current response exhibits the
      features of synaptic Short-Term Plasticity (STP) with facilitating or depressing
      response according to the stimulus frequency. We found that the response
      characteristic time upsilonSTP depends on dopamine (DA) concentration in
      solution. The dose curve exhibits superexponential sensitivity at the lowest
      concentrations below 1 nM. The sensor detects [DA] down to 1 pM range. We assess
      the sensor also in the presence of ascorbic acid (AA) and uric acid (UA). Our
      sensor does not respond to UA, but responds to AA only at concentration above 100
      MUM. However, it is still able to detect DA down to 1 pM range in the presence of
      [AA] = 100 MUM and 100 pM in the presence of [UA] = 3 MUM, these values for AA
      and UA being the physiological levels in the cerebrospinal fluid and the
      striatum, respectively.

PMID- 29226669
TI  - Enhanced Oxidation-Resistant Cu@Ni Core-Shell Nanoparticles for Printed Flexible
      Electrodes.
AB  - In this work, the fabrication and application of highly conductive, robust,
      flexible, and oxidation-resistant Cu-Ni core-shell nanoparticle (NP)-based
      electrodes have been reported. Cu@Ni core-shell NPs with a tunable Ni shell
      thickness were synthesized by varying the Cu/Ni molar ratios in the precursor
      solution. Through continuous spray coating and flash photonic sintering without
      an inert atmosphere, large-area Cu@Ni NP-based conductors were fabricated on
      various polymer substrates. These NP-based electrodes demonstrate a low sheet
      resistance of 1.3 Omega sq-1 under an optical energy dose of 1.5 J cm-2. In
      addition, they exhibit highly stable sheet resistances (DeltaR/R0 < 1) even after
      30 days of aging at 85  degrees C and 85% relative humidity. Further, a flexible
      heater fabricated from the Cu@Ni film is demonstrated, which shows uniform heat
      distribution and stable temperature compared to those of a pure Cu film.

PMID- 29226670
TI  - Carrier Trapping by Oxygen Impurities in Molybdenum Diselenide.
AB  - Understanding defect effect on carrier dynamics is essential for both fundamental
      physics and potential applications of transition metal dichalcogenides (TMDs).
      Here, the phenomenon of oxygen impurities trapping photoexcited carriers has been
      studied with ultrafast pump-probe spectroscopy. Oxygen impurities are
      intentionally created in exfoliated multilayer MoSe2 with Ar+ plasma irradiation
      and air exposure. After plasma treatment, the signal of transient absorption
      first increases and then decreases, which is a signature of defect-capturing
      carriers. With larger density of oxygen defects, the trapping effect becomes more
      prominent. The trapping defect densities are estimated from the transient
      absorption signal, and its increasing trend in the longer-irradiated sample
      agrees with the results from X-ray photoelectron spectroscopy. First-principle
      calculations with density functional theory reveal that oxygen atoms occupying Mo
      vacancies create mid-gap defect states, which are responsible for carrier
      trapping. Our findings shed light on the important role of oxygen defects as
      carrier trappers in TMDs, and facilitate defect engineering in relevant materials
      and device applications.

PMID- 29226671
TI  - A Multifunctional Reactor with Dry-Stored Reagents for Enzymatic Amplification of
      Nucleic Acids.
AB  - To enable inexpensive molecular detection at the point-of-care and at home with
      minimal or no instrumentation, it is necessary to streamline unit operations and
      store reagents refrigeration-free. To address this need, a multifunctional
      enzymatic amplification reactor that combines solid-phase nucleic acid
      extraction, concentration, and purification; refrigeration-free storage of
      reagents with just-in-time release; and enzymatic amplification is designed,
      prototyped, and tested. A nucleic acid isolation membrane is placed at the
      reactor's inlet, and paraffin-encapsulated reagents are prestored within the
      reactor. When a sample mixed with chaotropic agents is filtered through the
      nucleic acid isolation membrane, the membrane binds nucleic acids from the
      sample. Importantly, the sample volume is decoupled from the reaction volume,
      enabling the use of relatively large sample volumes for high sensitivity. When
      the amplification reactor's temperature increases to its operating level, the
      paraffin encapsulating the reagents melts and moves out of the way. The reagents
      are hydrated, just-in-time, and the polymerase reaction proceeds. The
      amplification process can be monitored, in real-time. We demonstrate our
      reactors' ability to amplify both DNA and RNA targets using polymerase with both
      reverse-transcriptase and strand displacement activities to obtain sensitivities
      on-par with benchtop equipment and a shelf life exceeding 6 months.

PMID- 29226672
TI  - Tuning the Swing Effect by Chemical Functionalization of Zeolitic Imidazolate
      Frameworks.
AB  - Many zeolitic imidazolate frameworks (ZIFs) are promising candidates for use in
      separation technologies. Comprising large cavities interconnected by small
      windows they can be used, at least in principle, as molecular sieves where
      molecules smaller than the window size are able to diffuse into the material
      while larger molecules are rejected. However, "swing effect" or "gate opening"
      phenomena resulting in an enlargement of the windows have proven to be
      detrimental. Here, we present the first systematic experimental and computational
      study of the effect of chemical functionalization of the imidazole linker on the
      framework dynamics. Using high-pressure (HP) single-crystal X-ray diffraction,
      density functional theory, and grand canonical Monte Carlo simulations, we show
      that in the isostructural ZIF-8, ZIF-90, and ZIF-65 functional groups of
      increasing polarity (-CH3, -CHO, and -NO2) on the imidazole linkers provide
      control over the degree of rotation and thus the critical window diameter. On
      application of pressure, the substituted imidazolate rings rotate, resulting in
      an increase in both pore volume and content. Our results show that the interplay
      between the guest molecules and the chemical function of the imidazole linker is
      essential for directing the swing effect in ZIF frameworks and therefore the
      adsorption performance.

PMID- 29226673
TI  - Multiplexed Detection of Attomoles of Nucleic Acids Using Fluorescent
      Nanoparticle Counting Platform.
AB  - The sensitive multiplexed detection of nucleic acids in a single sample by a
      simple manner is of pivotal importance for the diagnosis and therapy of human
      diseases. Herein, we constructed an automatic fluorescent nanoparticle (FNP)
      counting platform with a common fluorescence microscopic imaging setup for
      nonamplification multiplexed detection of attomoles of nucleic acids. Taking the
      advantages of the highly bright, multicolor emitting FNPs and magnetic
      separation, the platform enables sensitive multiplexed detection without the need
      for extra fluorescent labels. Quantification for multiplex DNAs, multiplex
      microRNAs (miRNA), as well as a DNA and miRNA mixture was achieved with a similar
      dynamic range, a limit of detection down to 5 amol (5 MUL detection volume), and
      a 81-115% spike recovery from different biological sample matrices. In
      particular, the sensitivity for multiplex miRNA is by far among the highest
      without using amplification or the lock nucleic acid hybridization enhancement
      strategy. Results regarding miRNA-141 from four different cell lines were
      agreeable with those of the quantitative reverse transcription polymerase chain
      reaction. Simultaneous detection of miRNA-141 and miRNA-21 in four different cell
      lines yielded consistent results with publications, indicating the potential for
      monitoring multiplex miRNA expression associated with the collaborative
      regulation of important cellular events. This work expands the rule set of
      multiplex nucleic acid detection strategies and shows promising potential
      application in clinical diagnosis.

PMID- 29226674
TI  - Indium Catalyzed Hydrofunctionalization of Styrene Derivatives Bearing a Hydroxy
      Group with Organosilicon Nucleophiles.
AB  - Hydrofunctionalization is one of the most important transformation reactions of
      alkenes. Herein, we describe the development of an indium-triiodide-catalyzed
      hydrofunctionalization of alkenes bearing a hydroxy group using various types of
      organosilicon nucleophiles. Indium triiodide was the most effective catalyst,
      whereas typical Lewis acids such as TiCl4, AlCl3, and BF3.OEt2 were ineffective.
      Many functional groups were successfully introduced, and these resulted in yields
      of 31-86%. Various styrene derivatives were also applicable to this reaction.
      Mechanistic investigation revealed that the present hydrofunctionalization
      proceeded through Bronsted acid-catalyzed intramolecular hydroalkoxylation of
      alkenes followed by InI3-catalyzed substitution reaction of cyclic ether
      intermediates.

PMID- 29226675
TI  - Ferroelectric Polarization-Modulated Interfacial Fine Structures Involving Two
      Dimensional Electron Gases in Pb(Zr,Ti)O3/LaAlO3/SrTiO3 Heterostructures.
AB  - Interfacial fine structures of bare LaAlO3/SrTiO3 (LAO/STO) heterostructures are
      compared with those of LAO/STO heterostructures capped with upward-polarized
      Pb(Zr0.1,Ti0.9)O3 (PZTup) or downward-polarized Pb(Zr0.5,Ti0.5)O3 (PZTdown)
      overlayers by aberration-corrected scanning transmission electron microscopy
      experiments. By combining the acquired electron energy-loss spectroscopy mapping,
      we are able to directly observe electron transfer from Ti4+ to Ti3+ and ionic
      displacements at the interface of bare LAO/STO and PZTdown/LAO/STO
      heterostructure unit cell by unit cell. No evidence of Ti3+ is observed at the
      interface of the PZTup/LAO/STO samples. Furthermore, the confinement of the two
      dimensional electron gas (2DEG) at the interface is determined by atomic-column
      spatial resolution. Compared with the bare LAO/STO interface, the 2DEG density at
      the LAO/STO interface is enhanced or depressed by the PZTdown or PZTup overlayer,
      respectively. Our microscopy studies shed light on the mechanism of ferroelectric
      modulation of interfacial transport at polar/nonpolar oxide heterointerfaces,
      which may facilitate applications of these materials as nonvolatile memory.

PMID- 29226676
TI  - Metal-Free Synthesis of Unsymmetrical Ureas and Carbamates from CO2 and Amines
      via Isocyanate Intermediates.
AB  - A mild and metal-free synthesis of aryl isocyanates from arylamines under an
      atmosphere of CO2 was developed. The carbamic acid intermediate, derived from the
      arylamine starting material and CO2 in the presence of DBU, is dehydrated by
      activated sulfonium reagents to generate the corresponding isocyanate. The latter
      can be detected by in situ IR and trapped by various amines and alcohols to make
      unsymmetrical ureas and carbamates, respectively. Dicarbamates can also be
      prepared in good yields via the mild dehydration of the corresponding dicarbamic
      acids.

PMID- 29226677
TI  - Tuning the Two-Dimensional Electron Gas at Oxide Interfaces with Ti-O
      Configurations: Evidence from X-ray Photoelectron Spectroscopy.
AB  - A chemical redox reaction can lead to a two-dimensional electron gas at the
      interface between a TiO2-terminated SrTiO3 (STO) substrate and an amorphous
      LaAlO3 capping layer. When replacing the STO substrate with rutile and anatase
      TiO2 substrates, considerable differences in the interfacial conduction are
      observed. On the basis of X-ray photoelectron spectroscopy (XPS) and transport
      measurements, we conclude that the interfacial conduction comes from redox
      reactions, and that the differences among the materials systems result mainly
      from variations in the activation energies for the diffusion of oxygen vacancies
      at substrate surfaces.

PMID- 29226678
TI  - Zinc and Magnesium Catalysts for the Hydrosilylation of Carbon Dioxide.
AB  - The terminal zinc and magnesium hydride compounds, [kappa3-TismPriBenz]ZnH and
      [TismPriBenz]MgH, which feature the tris[(1-isopropylbenzimidazol-2
      yl)dimethylsilyl]methyl ligand, react with B(C6F5)3 to afford the ion pairs,
      {[TismPriBenz]M}[HB(C6F5)3] (M = Zn, Mg), which are rare examples of these metals
      in trigonal monopyramidal coordination environments. Significantly, in
      combination with B(C6F5)3, {[TismPriBenz]M}-[HB(C6F5)3] generates catalytic
      systems for the hydrosilylation of CO2 by R3SiH to afford sequentially the
      bis(silyl)acetal, H2C(OSiR3)2, and CH4 (R3SiH = PhSiH3, Et3SiH, and Ph3SiH). In
      contrast to many other catalysts for these transformations, both the zinc and
      magnesium catalytic systems are active at room temperature, and the latter
      provides the first example of catalytic hydrosilylation of CO2 involving a
      magnesium compound. Also of note, the selectivity of the catalytic systems may be
      controlled by the nature of the silane, with PhSiH3 favoring CH4, and Ph3SiH
      favoring the bis(silyl)acetal, H2C(OSiPh3)2.

PMID- 29226679
TI  - Controllable Synthesis of Two-Dimensional Ruddlesden-Popper-Type Perovskite
      Heterostructures.
AB  - Two-dimensional Ruddlesden-Popper type perovskites (2D perovskites) have recently
      attracted increasing attention. It is expected that 2D perovskite-based
      heterostructures can significantly improve the efficiency of the optoelectronic
      devices and extend the material functionalities; however, rational synthesis of
      such heterostructures has not been realized to date. We report on a general low
      temperature synthetic strategy for the synthesis of 2D perovskite-based lateral
      and vertical (n-CH3(CH2)3NH3)2PbI4/(n-CH3(CH2)3NH3)2(CH3NH3)Pb2I7
      heterostructures for the first time. A combination of solution synthesis and gas
      solid phase intercalation approach allows us to efficiently synthesize both
      lateral and vertical heterostructures with great flexibility. X-ray diffraction,
      photoluminescence, and photoluminescence excitation mapping and electrical
      transport measurement studies reveal the successful synthesis of lateral and
      vertical heterostructures with precisely spatial-modulation control and
      distinguishable interfaces. Our studies not only provide an efficient synthetic
      strategy with great flexibility, enabling us to create 2D perovskite-based
      heterostructures, but also offer a platform to investigate the physical processes
      in those heterostructures.

PMID- 29226681
TI  - Protein Nanotube Selectively Cleavable with DNA: Supramolecular Polymerization of
      "DNA-Appended Molecular Chaperones".
AB  - Here, we report molecular chaperone GroELs that carry, at their apical domains,
      multiple DNA strands (ideally 28 DNA strands in total) with defined
      oligonucleotide (nt) sequences. This design strategy allows for the preparation
      of GroEL10a and GroEL10b carrying 10-nt DNA strands of 10a and 10b with
      complementary sequences, respectively, at their apical domains. One-dimensional
      coassembly of these GroELs is possible to form protein nanotube NT10a/10b with an
      anomalous thermodynamic stability due to the exceptionally large multivalency for
      the coassembly. Likewise, comparably stable nanotube NT15c/10d was obtained even
      when the apical-domain DNA strands (15c and 10d) were partially complementary to
      one another. Nevertheless, in sharp contrast with NT10a/10b, NT15c/10d, when
      incubated with DNA 15d, dissociates rapidly and completely because 15d
      preferentially hybridizes with the DNA strands of 15c in NT15c/10d by displacing
      those of 10d, to afford a mixture of GroEL15c/15d and GroEL10d. Even in the
      presence of NT10c/10d, 15d cleaved off NT15c/10d selectively, indicating the
      potential utility of NTs for targeted delivery.

PMID- 29226680
TI  - Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand
      Exchange in Ru(II) Complexes.
AB  - Four Ru(II) complexes were prepared bearing two new tetradentate ligands, cyTPA
      and 1-isocyTPQA, which feature a piperidine ring that provides a structurally
      rigid backbone and facilitates the installation of other donors as the fourth
      chelating arm, while avoiding the formation of stereoisomers. The photophysical
      properties and photochemistry of [Ru(cyTPA)(CH3CN)2]2+ (1), [Ru(1
      isocyTPQA)(CH3CN)2]2+ (2), [Ru(cyTPA)(py)2]2+ (3), and [Ru(1-isocyTPQA)(py)2]2+
      (4) were compared. The quantum yield for the CH3CN/H2O ligand exchange of 2 was
      measured to be Phi400 = 0.033(3), 5-fold greater than that of 1, Phi400 =
      0.0066(3). The quantum yields for the py/H2O ligand exchange of 3 and 4 were
      lower, 0.0012(1) and 0.0013(1), respectively. DFT and related calculations show
      the presence of a highly mixed 3MLCT/3pipi* excited state as the lowest triplet
      state in 2, whereas the lowest energy triplet states in 1, 3, and 4 were
      calculated to be 3LF in nature. The mixed 3MLCT/3pipi* excited state places
      significant spin density on the quinoline moiety of the 1-isocyTPQA ligand
      positioned trans to the photolabile CH3CN ligand in 2, suggesting the presence of
      a trans-type influence in the excited state that enhances ligand exchange.
      Ultrafast spectroscopy was used to probe the excited states of 1-4, which
      confirmed that the mixed 3MLCT/3pipi* excited state in 2 promotes ligand
      dissociation, representing a new manner to effect photoinduced ligand exchange.
      The findings from this work can be used to design improved complexes for
      applications that require efficient ligand dissociation, as well as for those
      that require minimal deactivation of the 3MLCT state through low-lying metal
      centered states.

PMID- 29226682
TI  - First Evaluation of Radioiodinated Flavonoids as Necrosis-Avid Agents and
      Application in Early Assessment of Tumor Necrosis.
AB  - A rapid and accurate identification of necrotic tissues is of great importance to
      define disease severity, predict prognosis, and monitor responses to therapies.
      To seek necrosis-avid agents with clinically translational potential, we first
      evaluated the necrosis avidity of flavonoids in rodent models of muscular,
      myocardial, and tumoral necrosis. In this study, the necrosis avidity of eight
      radioiodinated 5,7-dihydroxyflavones was tested by ex vivo gamma counting,
      histochemical staining, and autoradiography in mouse models of ethanol-induced
      muscular necrosis. The necrosis avidity of a lead tracer, 131I-5, was further
      assessed in rat models of myocardial infarction and reperfusion. Therapy response
      was evaluated by 131I-5 single photon emission computed tomography/computed
      tomography imaging 24 h after combretastatin A-4 disodium phosphate (CA4P)
      therapy on rats bearing W256 breast carcinomas. The necrosis avidity mechanism
      for the tracers was studied by in vitro DNA binding experiments of 12 5,7
      dihydroxyflavones and in vivo blocking experiments of 131I-5. In the results, all
      131I-5,7-dihydroxyflavones showed intense uptake to necrotic muscles, and 131I-5
      emerged as the most potential tracer among them. 131I-5 obtained a necrotic
      viable myocardium ratio of 5.0 +/- 0.9 in post-mortem biodistribution on
      reperfused myocardial infarction models and achieved necrosis imaging on CA4P
      treated W256 tumors 4 h after tracer injection. DNA binding studies suggested
      that necrosis avidity was related to DNA binding to a certain extent. The uptake
      of 131I-5 in necrotic muscle was markedly blocked by excessive ethidium bromide
      and cold 5 with a 51.95% and 64.29% decline at 1 h after coinjection,
      respectively. In conclusion, flavonoids are necrosis-avid agents. Furthermore,
      131I-5 can serve as a promising necrosis-avid diagnostic tracer for the rapid
      imaging of necrotic tissues, supporting the further molecular design of
      radiotracer based on 5.

PMID- 29226683
TI  - Permeability Barriers for Nicotine and Mannitol in Porcine Buccal Mucosa Studied
      by High-Resolution MALDI Mass Spectrometry Imaging.
AB  - Improved nicotine permeability across buccal mucosa may enable more effective
      oromucosal nicotine replacement therapy products. It is essential to know the
      location and composition of the main barrier for drug diffusion to enhance the
      drug permeability. Matrix-assisted laser desorption ionization mass spectrometry
      imaging (MALDI MSI) is a rapidly evolving technique that can be used to image the
      spatial distribution of drugs and drug metabolites in tissue cryo-sections,
      without prior labeling of the drug. In this study, the distribution of nicotine
      and mannitol in porcine buccal mucosa was imaged with 10 MUm spatial resolution
      after apical as well as submucosal application of the drugs in order to localize
      the main permeability barrier(s). This was supported by ex vivo permeability
      studies across separated porcine buccal epithelium and submucosa. Lastly, the
      metabolism of nicotine in porcine buccal mucosa was evaluated by imaging of the
      main metabolite, cotinine. The results showed that the main permeability barrier
      to both nicotine and mannitol was located in the outer fourth of the epithelium.
      Further, it was shown that cotinine was sparsely distributed in excised porcine
      buccal mucosa, indicating that nicotine metabolism in excised porcine buccal
      mucosa was negligible. MALDI MSI was shown to be a useful method for imaging
      spatial distribution of drugs in buccal mucosa.

PMID- 29226684
TI  - Quantum Dot Based Luminescent Nanoprobes for Sigma-2 Receptor Imaging.
AB  - The increasing importance of sigma-2 receptor as target for the diagnosis and
      therapy of tumors paves the way for the development of innovative optically
      traceable fluorescent probes as tumor cell contrast and therapeutic agents. Here,
      a novel hybrid organic-inorganic nanostructure is developed by combining the
      superior fluorescent properties of inorganic quantum dots (QDs), coated with a
      hydrophilic silica shell (QD@SiO2 NPs), the versatility of the silica shell, and
      the high selectivity for sigma-2 receptor of the two synthetic ligands, namely,
      the 6-[(6-aminohexyl)oxy]-2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)
      yl)propyl)-3,4-dihydroisoquinolin-1(2H)-one (MLP66) and 6-[1-[3-(4
      cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine
      (TA6). The proposed nanostructures represent a challenging alternative to all
      previously studied organic small fluorescent molecules, based on the same sigma-2
      receptor affinity moieties. Flow cytometry and confocal fluorescence microscopy
      experiments, respectively, on fixed and living cancerous MCF7 cells, which
      overexpress the sigma-2 receptor, prove the ability of functionalized (QD@SiO2
      TA6 and QD@SiO2-MLP66) NPs to be internalized and demonstrate their affinity to
      the sigma-2 receptor, ultimately validating the targeting properties conveyed to
      the NPs by sigma-2 ligand conjugation. The presented QD-based nanoprobes possess
      a great potential as in vitro selective sigma-2 receptor imaging agent and,
      consequently, could provide a significant impact to future theranostic
      applications.

PMID- 29226685
TI  - Size Effect on Lipid Nanocapsule-Mediated GLP-1 Secretion from Enteroendocrine L
      Cells.
AB  - L cells are enteroendocrine cells located throughout the gastrointestinal tract
      that secrete physiologically important peptides. The most characterized peptides
      secreted by L cells are the peptide YY (PYY) and the glucagon-like peptides 1
      (GLP-1) and 2 (GLP-2). These peptides are released rapidly into the circulation
      after oral nutrient ingestion. Recently, lipid-based nanoparticles (NP) have been
      described as triggers for GLP-1 secretion by L cells. NP physicochemical
      properties play a key role in the NP-cell interaction, and drive NP cell
      internalization. We herein hypothesize that lipid-based NP with appropriate size
      would not only be able to deliver drugs into blood circulation but also act like
      endogenous ligands to stimulate GLP-1 secretion. We tested five different size
      (25, 50, 100, 150, and 200 nm) lipid nanocapsules (LNC) on murine L cells in
      vitro to confirm this hypothesis. Our study showed that GLP-1 secretion was
      induced only by the 200 nm size LNC, highlighting the importance of LNC particle
      size on the secretion of GLP-1 by L cells. The different formulations did not
      affect proglucagon mRNA expression, suggesting that there was not an increased
      GLP-1 synthesis. As a proof of concept, we further demonstrated in normoglycemic
      mice that 200 nm LNC administration increases GLP-1 levels by 4- and 3-fold
      compared to untreated control mice 60 and 180 min after the administration,
      respectively. Our study suggests that 200 nm LNC as a nanocarrier to encapsulate
      drug candidates and as a ligand to induce endogenous GLP-1 secretion might
      represent a promising strategy for type 2 diabetes mellitus treatment.

PMID- 29226687
TI  - Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced
      Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development.
AB  - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primate
      (NHP) has been described as the most translatable model for experimental
      reproduction of L-dopa-induced dyskinesia (LID). However, from a drug discovery
      perspective, the risk associated with investment in this type of model is high
      due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is
      recommended for testing compounds but relies on onerous, and nonstandard
      behavioral rating scales. We sought to develop a simplified and sensitive method
      aiming at assessing LID in the rat. The purpose was to validate a reliable tool
      providing earlier insight into the antidyskinetic potential of compounds in a
      time/cost-effective manner before further investigation in NHP models.
      Unilaterally 6-OHDA-lesioned rats were administered L-dopa (20 mg/kg) and
      benserazide (5 mg/kg) daily for 3 weeks starting 4 weeks postlesion, then
      coadministered with amantadine (20-30-40 mg/kg). An adapted rating scale was used
      to score LID frequency and a severity coefficient was applied depending on the
      features of the observed behavior. A gradual increase (about 3-fold) in LID score
      was observed over the 3 weeks of L-dopa treatment. The rating scale was sensitive
      enough to highlight a dose-dependent amantadine-mediated decrease (about 2.2
      fold) in LID score. We validated a simplified method, able to reflect different
      levels of severity in the assessment of LID and, thus, provide a reliable tool
      for drug discovery.

PMID- 29226686
TI  - Enhanced Specific Activity by Multichelation of Exendin-3 Leads To Improved Image
      Quality and In Vivo Beta Cell Imaging.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is
      a promising approach to noninvasively visualize and determine beta cell mass
      (BCM), which could help to unravel the pathophysiology of diabetes. However,
      saturation of the GLP-1R on beta cells occurs at low peptide doses, since the
      number of receptors expressed under physiological conditions is low. Therefore,
      tracers with high specific activities are required to sensitively image small
      variations in BCM. Here, we describe a novel exendin-3-based radiotracer with
      multiple chelators and determine its potential for in vivo beta cell imaging.
      Exendin-3 was modified by adding six lysine residues C-terminally conjugated with
      one, two, or six DTPA moieties. All compounds were labeled with 111In and their
      GLP-1R affinity was determined in vitro using GLP-1R expressing cells. The in
      vivo behavior of the 111In-labeled tracers was examined in BALB/c nude mice with
      a subcutaneous GLP-1R expressing tumor (INS-1). Brown Norway rats were used for
      SPECT visualization of the pancreatic BCM. Addition of six lysine and six DTPA
      residues (hexendin(40-45)) resulted in a 7-fold increase in specific activity
      (from 0.73 GBq/nmol to 5.54 GBq/nmol). IC50 values varied between 5.2 and 69.5
      nM. All compounds with two or six lysine and DTPA residues had a significantly
      lower receptor affinity than [Lys40(DTPA)]exendin-3 (4.4 nM, p < 0.05). The
      biodistribution in mice revealed no significant decrease in pancreatic uptake
      after addition of six lysine and DTPA molecules. Hexendin(40-45) showed a 6-fold
      increase in absolute 111In uptake in the pancreas of Brown Norway rats compared
      to [Lys40(DTPA)]exendin-3 (182.7 +/- 42.3 kBq vs 28.8 +/- 6.0 kBq, p < 0.001).
      Visualization of the pancreas on SPECT was improved using hexendin(40-45), due to
      the higher count rate, achieved at the same peptide dose. In conclusion,
      hexendin(40-45) showed an improved visualization of the pancreas with SPECT. This
      tracer holds promise to sensitively and specifically detect small variations in
      BCM.

PMID- 29226688
TI  - Performance Limits of Luminescent Solar Concentrators Tested with Seed/Quantum
      Well Quantum Dots in a Selective-Reflector-Based Optical Cavity.
AB  - Luminescent solar concentrators (LSCs) can serve as large-area sunlight
      collectors for photovoltaic devices. An important LSC characteristic is a
      concentration factor (C), which is defined as the ratio of the output and the
      input photon flux densities. This parameter can be also thought of as an
      effective enlargement factor of a solar cell active area. On the basis of
      thermodynamic considerations, the C-factor can reach extremely high values that
      exceed those accessible with traditional concentrating optics. In reality,
      however, the best reported values of C are around 30. Here we demonstrate that
      using a new type of high-emissivity quantum dots (QDs) incorporated into a
      specially designed cavity, we are able to achieve the C of ~62 for spectrally
      integrated emission and ~120 for the red portion of the photoluminescence
      spectrum. The key feature of these QDs is a seed/quantum-well/thick-shell design,
      which allows for obtaining a high emission quantum yield (>95%) simultaneously
      with a large LSC quality factor (QLSC of ~100) defined as the ratio of absorption
      coefficients at the wavelengths of incident and reemitted light. By incorporating
      the QDs into a specially designed cavity equipped with a top selective reflector
      (a Bragg mirror or a thin silver film), we are able to effectively recycle
      reemitted light achieving light trapping coefficients of ~85%. The observed
      performance of these devices is in remarkable agreement with analytical modeling,
      which allows us to project that the applied approach should allow one to boost
      the spectrally integrated concentration factors to more than 100 by further
      improving light trapping and/or increasing QLSC.

PMID- 29226689
TI  - Simultaneous Multislice Resting-State Functional Magnetic Resonance Imaging at 3
      Tesla: Slice-Acceleration-Related Biases in Physiological Effects.
AB  - Simultaneous multislice echo-planar imaging (SMS-EPI) can enhance the
      spatiotemporal resolution of resting-state functional MRI (rs-fMRI) by encoding
      and simultaneously imaging "groups" of slices. However, phenomena, including
      respiration, cardiac pulsatility, respiration volume per time (RVT), and cardiac
      rate variation (CRV), referred to as "physiological processes," impact SMS-EPI rs
      fMRI in a manner that is yet to be well characterized. In particular,
      physiological noise may incur aliasing and introduce spurious signals from one
      slice into another within the "slice group" in rs-fMRI data, resulting in a
      deleterious effect on resting-state functional connectivity MRI (rs-fcMRI) maps.
      In the present work, we aimed to quantitatively compare the effects of
      physiological noise on regular EPI and SMS-EPI in terms of rs-fMRI data and
      resulting functional connectivity measurements. We compare SMS-EPI and regular
      EPI data acquired from 11 healthy young adults with matching parameters. The
      physiological noise characteristics were compared between the two data sets
      through different combinations of physiological regression steps. We observed
      that the physiological noise characteristics differed between SMS-EPI and regular
      EPI, with cardiac pulsatility contributing more to noise in regular EPI data but
      low-frequency heart rate variability contributing more to SMS-EPI. In addition, a
      significant slice-group bias was observed in the functional connectivity density
      maps derived from SMS-EPI data. We conclude that making appropriate corrections
      for physiological noise is likely more important for SMS-EPI than for regular EPI
      acquisitions.

PMID- 29226691
TI  - Could the nicotine receptor partial agonist varenicline moderate manic symptoms
      in heavy smokers with manic episodes?

PMID- 29226690
TI  - Low Levels of Endothelial Progenitor Cells and Their Association with Systemic
      Inflammation and Monocyte Activation in Older HIV-Infected Men.
AB  - Endothelial progenitor cells (EPCs) repair damaged vascular endothelium, and low
      circulating EPC levels have been associated with cardiovascular disease (CVD).
      CD34+/KDR+ EPCs are commonly reported in the literature and CD34+/CD133+/KDR+
      EPCs are rare in circulation but highly specific for endothelial lineage. HIV
      infected (HIV+) adults have chronic inflammation and increased CVD risk, but the
      relationship between CVD, vascular inflammation, and EPCs in HIV remains unclear.
      In a pilot study, EPCs were measured in 57 HIV+ men [>=50 years old, HIV-1 RNA
      <50 copies/ml on antiretroviral therapy (ART)] by real-time flow cytometry using
      cellular immaturity (CD34 and/or CD133) and endothelial commitment (KDR) markers.
      Fasting inflammatory biomarker levels were measured by ELISA. Median age was 57
      years; CD4+ T lymphocyte count was 570 cells/mm3. Prevalent CVD risk factors
      included 16% diabetes, 28% hypertension, 53% dyslipidemia, and 33% smoking.
      Median (interquartile range) EPC values were CD34+/KDR+ 0.1 (0.0-0.9) cells/105
      peripheral blood mononuclear cells (PBMCs) and CD34+/CD133+/KDR+ 0.1 (0.0-0.9)
      cells/105 PBMCs. We observed a high prevalence of undetectable CD34+/KDR+ (40%)
      and CD34+/CD133+/KDR+ EPCs (44%). Men with undetectable EPCs were more likely to
      have >=2 CVD risk factors, lower interleukin-6 (IL-6), and higher sCD163 levels.
      In these older HIV+ men on suppressive ART, CD34+/KDR+ and CD34+/CD133+/KDR+ EPC
      levels were low and often undetectable. Undetectable EPC levels were associated
      with greater CVD risk factor burden, lower IL-6 (consistent with decreased EPC
      production stimulus), and higher sCD163 (consistent with monocyte activation and
      prior CVD associations) levels, suggesting a potential relationship between EPCs
      and atherosclerotic burden in this population.

PMID- 29226692
TI  - Identification of a Novel HIV-1 Unique Recombinant Form Between B, CRF01_AE and
      CRF07_BC in Men Who Have Sex with Men in Guangxi, China.
AB  - B, CRF01_AE and CRF07_BC are three major HIV-1 subtypes circulating in China.
      Here we detected a novel CCR5-tropic HIV-1 recombinant virus (GX2016EU23), which
      was isolated from an HIV-1-infected man who had sex with men (MSM) in Guangxi,
      China. Phylogenetic analysis of the near full-length genome showed that
      GX2016EU23 consisted of at least seven segments, that is two B, two CRF01_AE, and
      three CRF07_BC segments. Recombinant breakpoints of GX2016EU23 were observed in
      the gag, pol, rev, and env regions. This is the first detection of a novel HIV-1
      recombinant (B/CRF01_AE/CRF07_BC) in MSM in Guangxi. The emergence of this novel
      recombinant suggests the increasing genetic diversity of the HIV-1 epidemic among
      the MSM group in China.

PMID- 29226693
TI  - Higher pulse pressure and risk for cardiovascular events in patients with
      essential hypertension: The Campania Salute Network.
AB  - Background Increased pulse pressure is associated with structural target organ
      damage, especially in elderly patients, increasing cardiovascular risk. Design In
      this analysis, we investigated whether high pulse pressure retains a prognostic
      effect also when common markers of target organ damage are taken into account.
      Methods We analysed an unselected cohort of treated hypertensive patients from
      the Campania Salute Network registry ( n = 7336). Participants with available
      cardiac and carotid ultrasound were required to be free of prevalent
      cardiovascular disease, with ejection fraction >=50%, and no more than stage III
      Chronic Kidney Disease. The median follow-up was 41 months and end-point was
      occurrence of major cardiovascular events (i.e. fatal and non-fatal stroke or
      myocardial infarction and sudden death). Based on current guidelines, pulse
      pressure >=60 mm Hg was classified as high pulse pressure ( n = 2356), at the
      time of the initial visit, whereas pulse pressure <60 mm Hg was considered normal
      ( n = 4980). Results High pulse pressure patients were older, more likely to be
      women and diabetic, while receiving more antihypertensive medications than normal
      pulse pressure (all p < 0.0001). High pulse pressure exhibited greater prevalence
      of left ventricular hypertrophy, and carotid plaque than normal pulse pressure
      (all p < 0.0001). In Cox regression, high pulse pressure patients had 57%
      increased hazard of major cardiovascular events, compared to normal pulse
      pressure (hazard ratio = 1.57; 95% confidence interval: 1.12-2.22, p = 0.01), an
      effect that was independent of significant prognostic impact of older age, male
      sex, diabetes, left ventricular hypertrophy, carotid plaque and less prescription
      of anti-renin-angiotensin system therapy. Conclusions High pulse pressure is a
      functional marker of target organ damage, predicting cardiovascular events in
      hypertensive patients, even independently of well-known structural markers of
      target organ damage.

PMID- 29226694
TI  - Effectiveness of motivational interviewing for improving physical activity self
      management for adults with type 2 diabetes: A review.
AB  - Objectives This review examines the effectiveness of motivational interviewing
      for physical activity self-management for adults diagnosed with diabetes mellitus
      type 2. Motivational interviewing is a patient centered individually tailored
      counseling intervention that aims to elicit a patient's own motivation for health
      behavior change. Review questions include (a) How have motivational interviewing
      methods been applied to physical activity interventions for adults with diabetes
      mellitus type 2? (b) What motivational interviewing approaches are associated
      with successful physical activity outcomes with diabetes mellitus 2? Methods
      Database searches used PubMed, CINAHL, and PsycINFO for the years 2000 to 2016.
      Criteria for inclusion was motivational interviewing used as the principal
      intervention in the tradition of Miller and Rollnick, measurement of physical
      activity, statistical significance reported for physical activity outcomes,
      quantitative research, and articles written in English. Results A total of nine
      studies met review criteria and four included motivational interviewing
      interventions associated with significant physical activity outcomes. Discussion
      Findings suggest motivational interviewing sessions should target a minimal
      number of self-management behaviors, be delivered by counselors proficient in
      motivational interviewing, and use motivational interviewing protocols with an
      emphasis placed either on duration or frequency of sessions.

PMID- 29226695
TI  - Racial disparities in health and health behaviors among gay, lesbian, bisexual
      and heterosexual men and women in the BRFSS-SOP.
AB  - OBJECTIVES: Research on sexual minority health lack examinations of how sexual
      orientation intersects with other identities, including racial/ethnic identity,
      to shape health outcomes among U.S. adults. This study examines how health status
      and health behavior varies for gay, lesbian, and bisexual men and women who
      identify as non-Hispanic white, non-Hispanic black, Latino, Asian/Pacific
      Islander, and American Indian/Alaskan Native. By examining health and health
      behaviors within and across sexual minority subgroups, our study reports on
      race/ethnic, gender, and sexual orientation specific health risks. METHODS: We
      respond to shortcomings in current data by utilizing aggregated data from
      fourteen states from the Behavioral Risk Factor Surveillance System (BRFSS)
      collected between 2005 and 2010 (n = 557,773). We investigated the odds of
      reporting poorer health, current cigarette smoking, and obesity by sexual
      orientation within race/ethnic and gender subgroups; all statistical analyses
      were performed in 2016. RESULTS: Results suggest persistent health and behavior
      disadvantages for lesbian and bisexual women of all racial and ethnic identities,
      relative to heterosexuals. Some of the heightened odds are extreme. Asian/Pacific
      Islander lesbian (OR = 3.92) and bisexual (OR = 4.61) women, for example, have
      4.0 times higher odds of smoking than heterosexual A/PI women. Results for men
      are more variable. To illustrate, the odds of obesity for White and A/PI men are
      indistinguishable between bisexuals and heterosexuals, and Black and American
      Indian/Alaskan Native bisexuals have lower odds of obesity than their
      heterosexual counterparts. CONCLUSION: These findings highlight the need for
      policy efforts aimed at improving health and health behaviors among lesbian and
      bisexual women across groups, and more targeted efforts among sexual minority
      men.

PMID- 29226696
TI  - To change or not to change - That is the question: A qualitative study of
      lifestyle changes following acute myocardial infarction.
AB  - Objective The purpose of this study was to investigate key factors related to
      lifestyle changes following acute myocardial infarction (AMI) by eliciting
      survivors' subjective needs for, attitudes towards and experiences with behaviour
      changes in their everyday life to improve future interventions promoting
      lifestyle changes. Methods Semi-structured interviews were conducted with 21
      individuals who had recently experienced an AMI. The interviews were audio
      recorded and transcribed verbatim. The data were analysed using qualitative
      content analysis. Results The data analysis revealed that lifestyle changes
      following AMI are influenced by a combination of individual (physical and
      psychological) and social factors that can be grouped into facilitators and
      barriers. The interviews indicated the need for more personalised information
      regarding the causes and risk factors of illness, the benefits of lifestyle
      changes and the importance of including significant others in lifestyle advice
      and education and of individualising support. Discussion Lifestyle change is a
      continuous process that is not completed within a few months after a cardiac
      event. Considering the identified themes when developing interventions to promote
      lifestyle changes following AMI may enhance the effectiveness and sustainability
      of such interventions.

PMID- 29226697
TI  - Update on the use of direct oral anticoagulants for the prevention and treatment
      of thromboembolism.
AB  - Following publication of our review article 4 years ago, there has been an uptake
      in the use of nonvitamin K oral antagonists, also known as direct oral
      anticoagulants. The most recent Xa inhibitors to receive approval are edoxaban,
      which has been approved for use in both atrial fibrillation and venous
      thromboembolism prevention and betrixaban, which has been approved in the USA for
      extended thromboprophylaxis in the medically ill population. Additional analyses
      of certain types of atrial fibrillation patients have now become available.
      Ongoing prescriber vigilance is recommended as additional information continues
      to emerge with this class of medications. The purpose of this paper is to provide
      an update on the use of the direct oral anticoagulant agents for the prevention
      and treatment of thromboembolism.

PMID- 29226699
TI  - Acute Mental Status Change in an Adolescent Male.

PMID- 29226698
TI  - In vitro and in vivo activity of Manuka honey against NDM-1-producing Klebsiella
      pneumoniae ST11.
AB  - AIM: To determine the therapeutic potential of Manuka honey against New Delhi
      metallo-beta-lactamase-1-producing Klebsiella pneumoniae ST11 in vitro and in
      vivo. MATERIALS & METHODS: Carbapenamases and metallo-beta-lactamases-producing
      K. pneumoniae ST11 isolated from blood culture was confirmed by VITEK-2(r)
      system, matrix-assisted laser desorption ionization-time of flight and multilocus
      sequence typing, followed by determination of minimum inhibitory concentration
      (MUg/ml) using VITEK-2 system. Genetic analysis of bla NDM-1 was done by PCR,
      pulsed-field gel electrophoresis and DNA hybridization. In vitro and in vivo
      efficacy of Manuka honey was performed by microbroth dilution assay and BALB/c
      mice model respectively. RESULTS: K. pneumoniae ST11 displayed resistance to
      commonly used antibiotics. bla NDM-1 was located on 150 and 270kb plasmids.
      Minimum inhibitory concentration and minimum bactericidal concentration of Manuka
      honey was 30% (v/v) and substantial reduction of bacterial mean log value (>1
      log) was observed in mice. Histological analysis of mice liver and kidneys
      demonstrated mild to moderate inflammation. CONCLUSION: Manuka honey can be used
      as an alternate therapeutic approach for management of New Delhi metallo-beta
      lactamase-producing pathogens.

PMID- 29226700
TI  - Retrospective Correction of Physiological Noise: Impact on Sensitivity,
      Specificity, and Reproducibility of Resting-State Functional Connectivity in a
      Reading Network Model.
AB  - It is well accepted that physiological noise (PN) obscures the detection of
      neural fluctuations in resting-state functional connectivity (rsFC) magnetic
      resonance imaging. However, a clear consensus for an optimal PN correction (PNC)
      methodology and how it can impact the rsFC signal characteristics is still
      lacking. In this study, we probe the impact of three PNC methods: RETROICOR:
      (Glover et al., 2000 ), ANATICOR: (Jo et al., 2010 ), and RVTMBPM: (Bianciardi et
      al., 2009 ). Using a reading network model, we systematically explore the effects
      of PNC optimization on sensitivity, specificity, and reproducibility of rsFC
      signals. In terms of specificity, ANATICOR was found to be effective in removing
      local white matter (WM) fluctuations and also resulted in aggressive removal of
      expected cortical-to-subcortical functional connections. The ability of RETROICOR
      to remove PN was equivalent to removal of simulated random PN such that it
      artificially inflated the connection strength, thereby decreasing sensitivity.
      RVTMBPM maintained specificity and sensitivity by balanced removal of
      vasodilatory PN and local WM nuisance edges. Another aspect of this work was
      exploring the effects of PNC on identifying reading group differences. Most PNC
      methods accounted for between-subject PN variability resulting in reduced
      intersession reproducibility. This effect facilitated the detection of the most
      consistent group differences. RVTMBPM was most effective in detecting significant
      group differences due to its inherent sensitivity to removing spatially
      structured and temporally repeating PN arising from dense vasculature. Finally,
      results suggest that combining all three PNC resulted in "overcorrection" by
      removing signal along with noise.

PMID- 29226701
TI  - Parental happiness and strain among young adult parents diagnosed with Attention
      Deficit Hyperactivity Disorder.
AB  - This study used data from the National Longitudinal Study of Adolescent to Adult
      Health (Add Health) to examine whether young adult parents diagnosed with
      Attention Deficit Hyperactivity Disorder experience less parental happiness
      and/or more parental strain than their counterparts not diagnosed with Attention
      Deficit Hyperactivity Disorder. Results from logistic regression models indicated
      that young adult parents ever diagnosed with Attention Deficit Hyperactivity
      Disorder have significantly greater odds of feeling overwhelmed as parents and
      significantly lower odds of feeling close to their children or happy in their
      role as parents compared to those never diagnosed with Attention Deficit
      Hyperactivity Disorder. Potential implications of these results for scholars as
      well as health professionals treating adult Attention Deficit Hyperactivity
      Disorder patients with children are discussed.

PMID- 29226702
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli in wastewaters and
      refugee camp in Lebanon.
AB  - AIM: To evaluate the effects of population influx of refugees on the prevalence
      of extended-spectrum beta-lactamase-producing Escherichia coli in wastewater
      networks in Lebanon. MATERIALS & METHODS: Pulsed-field gel electrophoresis,
      multilocus sequence typing and antibiotic resistance genes typing were performed.
      RESULTS: 53.1% of isolates recovered from Al-Qaa refugee camp were positive for
      the tested resistant determinants compared with 49.1% from river effluents. All
      isolates carried aac(6)-1b and/or aac(3)-II; none carried armA, rmtB, ant(4')
      Iia, aph(3')-Ia or carbapenemases. CTX-M-15, TEM-1, OXA-1, CMY-2 and SHV-12 were
      detected. Single and/or double substitutions were detected in GyrA and ParC.
      Phylogenetic group B2 and ST6470 were the most prevalent. Pulsed-field gel
      electrophoresis revealed 19 XbaI patterns and 17 pulsotypes. CONCLUSION: The
      introduction of novel resistance patterns into the wastewater network requires
      effective control.

PMID- 29226704
TI  - HIV Cure Research Crowdsourcing: An Author Response.

PMID- 29226703
TI  - Sex Hormones Modulate the Relationship Between Global Advantage, Lateralization,
      and Interhemispheric Connectivity in a Navon Paradigm.
AB  - Sex, stimulus material, and attention condition have previously been related to
      global advantage (GA; faster responses to global targets than to local targets)
      on the one hand and lateralization during global-local processing on the other
      hand. It is presumed that the lateralization of brain functions is either related
      to the inhibitory influence of the dominant on the nondominant hemisphere or
      reduced excitation between hemispheres. However, a direct relationship between
      the GA and lateralization and interhemispheric connectivity has not been
      previously established. In this study, 58 participants (29 men, 29 naturally
      cycling women) completed a Navon paradigm, modulating attention condition
      (divided vs. focused) and stimulus material (letters vs. shapes) during
      functional magnetic resonance imaging. The size of the GA effect, lateralization
      indices, interhemispheric connectivity, and sex hormone levels were assessed. In
      summary, this study suggests that interhemispheric connectivity during global
      local processing is affected by sex and material. Furthermore, the relationship
      between interhemispheric connectivity, lateralization, and behavior was modulated
      by sex and sex hormones. Results suggest (1) differential roles of
      interhemispheric connectivity for lateralization in men and women and (2)
      differential roles of lateralization for behavior in men and women. Importantly,
      the classic assumption that a more negative connectivity leads to stronger
      lateralization, which in turn leads to a stronger GA effect, was observed in men,
      whereas the opposite pattern was found in women. The relationship between
      connectivity and lateralization was mediated through testosterone levels, whereas
      the relationship between lateralization and behavior was mediated through
      progesterone levels. Results are discussed in light of differential functions of
      inhibitory and excitatory interhemispheric processes in men and women.

PMID- 29226705
TI  - Survival prediction in pancreatic cancer patients with no distant metastasis: a
      large-scale population-based estimate.
AB  - AIM: To identify the risk factors for overall survival (OS) of pancreatic ductal
      adenocarcinoma patients with no distant metastasis, and formulate a novel
      nomogram for prognostic prediction. PATIENTS & METHODS: Data were obtained from
      Surveillance, Epidemiology, and End Results database of pancreatic ductal
      adenocarcinoma patients with no distant metastasis as the primary cohort, and 127
      patients at our institution were enrolled as the validation cohort. The
      prognostic nomogram integrating all independent risk factors for predicting OS
      was established to achieve superior discriminatory ability. RESULTS: The
      constructed nomogram showed excellent performance and superior predictive
      accuracy for OS according to the concordance index and calibration curve.
      CONCLUSION: One more advanced and accurate predictive model will be obtained to
      assist in risk stratification via the constructed nomogram.

PMID- 29226707
TI  - Managing anticoagulation in patients receiving implantable cardiac devices.
AB  - A substantial proportion of patients who undergo cardiac device implantation
      receive oral anticoagulation to prevent thromboembolism or antiplatelets to
      prevent thrombotic events. Anticoagulation and antiplatelets increase the risk of
      hemorrhagic complications, while discontinuation may increase thromboembolic risk
      and thrombotic events. With the introduction of non-vitamin K antagonist oral
      anticoagulant agents and the newer antiplatelet agents such as prasugrel or
      ticagrelor, the perioperative management of patients has become more challenging.
      In this article, we review the recent trials and meta-analysis and describe the
      available evidence, as well as the current recommendations in order to inform
      best practice. We also reinforce the importance of further trials in this complex
      and rapidly evolving area.

PMID- 29226706
TI  - Natural Products and HIV/AIDS.
AB  - The study of natural products in biomedical research is not a modern concept.
      Many of the most successful medical therapeutics are derived from natural
      products, including those studied in the field of HIV/AIDS. Biomedical research
      has a rich history of discovery based on screens of medicinal herbs and
      traditional medicine practices. Compounds derived from natural products, which
      repress HIV and those that activate latent HIV, have been reported. It is
      important to remember the tradition in medical research to derive therapies based
      on these natural products and to overcome the negative perception of natural
      products as an "alternative medicine."

PMID- 29226708
TI  - "Men Are in Front at Eating Time, but Not When It Comes to Rearing the Chicken":
      Unpacking the Gendered Benefits and Costs of Livestock Ownership in Kenya.
AB  - BACKGROUND: Livestock can promote resilience in low-income communities through a
      number of pathways. Livestock development programs seek to amplify these benefits
      but often fail to consider the costs to intended beneficiaries or the effect of
      prevailing gender norms. OBJECTIVE: To explore perceptions of livestock ownership
      among female smallholder livestock keepers in Nyanza Region, Kenya, and unpack
      how the distribution of livestock benefits and investments varies by gender
      within households. METHODS: We used multiple ethnographic techniques, including
      Photovoice, a photo-elicitation interview method, focus group discussions, and
      pile sorts, with female smallholder livestock owners (n = 18) participating in an
      ongoing cohort study. Transcripts were coded using a combination of a priori
      constructs and grounded theory. RESULTS: We found that livestock benefited
      households by providing financial security, food security, social benefits, and
      human time and labor savings. However, these benefits largely promoted long-term
      household resilience rather than immediate gains. Livestock ownership also had
      major costs to household time and labor, which were overwhelmingly borne by women
      and children. Despite this investment, women had limited livestock ownership
      rights, decision-making power, control over income, or access to meat.
      CONCLUSIONS: Our findings suggest that livestock ownership requires significant
      investments of household time and labor, which disproportionately burden women.
      Prevailing gender inequalities may therefore constrain the net benefit of
      livestock ownership for many women and their households in some contexts.
      Livestock development programs must assess both program benefits and costs at
      multiple levels to ensure that women's participation in livestock production
      leads to improved individual and household outcomes.

PMID- 29226709
TI  - Enhanced Brain Network Activity in Complex Movement Rhythms: A Simultaneous
      Functional Magnetic Resonance Imaging and Electroencephalography Study.
AB  - Generating movement rhythms is known to involve a network of distributed brain
      regions associated with motor planning, control, execution, and perception of
      timing for the repertoire of motor actions. What brain areas are bound in the
      network and how the network activity is modulated by rhythmic complexity have not
      been completely explored. To contribute to answering these questions, we designed
      a study in which nine healthy participants performed simple to complex rhythmic
      finger movement tasks while undergoing simultaneous functional magnetic resonance
      imaging and electroencephalography (fMRI-EEG) recordings of their brain activity
      during the tasks and rest. From fMRI blood oxygenation-level-dependent (BOLD)
      measurements, we found that the complexity of rhythms was associated with brain
      activations in the primary motor cortex (PMC), supplementary motor area (SMA),
      and cerebellum (Cb), and with network interactions from these cortical regions to
      the cerebellum. The spectral analysis of single-trial EEG source waveforms at the
      cortical regions further showed that there were bidirectional interactions
      between PMC and SMA, and the complexity of rhythms was associated with power
      spectra and Granger causality spectra in the beta (13-30 Hz) frequency band, not
      in the alpha (8-12 Hz) and gamma (30-58 Hz) bands. These results provide us new
      insights into the mechanisms for movement rhythm complexity.

PMID- 29226712
TI  - [Risk stratification before thoracic surgery, perioperative pulmonary
      rehabilitation].
AB  - INTRODUCTION: Besides the oncology and operative surgical technics, functional
      aspects influence the operability of lung cancer. Preoperative risk
      stratification, evaluation of postoperative complications needs to be considered.
      AIM: To review international literature and experiences of our institute. METHOD:
      We focused the literature of risk stratification of thoracic surgery. Lung
      function, lung mechanics, chest kinematics, exercise physiology were considered.
      Effectiveness of pulmonary rehabilitation for cardiovascular system, lung
      mechanics, muscles, exercise capacity and quality of life were evaluated.
      Laboratory parameters, comorbidities, obesity, cachexia, smoking cessation were
      considered. RESULTS: Elevated blood sugar, kidney function, reduced albumin level
      increased the risk. COPD, sleep apnoea, heart failure, obesity and cachexia
      influences the outcome. Smoking cessation may reduce postoperative complications.
      Controlled breathing technics, chest wall mobilization, training have favourable
      effects. Psychosocial support and dietetics are important. CONCLUSIONS: Risk
      stratification is supported by laboratory parameters, lung function, oxygen
      uptake and comorbidities. Pulmonary rehabilitation can improve functionality and
      quality of life. Orv Hetil. 2017; 158(50): 1989-1997.

PMID- 29226713
TI  - [Prognostic importance of lactate dehydrogenase (LDH) in oncology].
AB  - Glycolysis is increased in most of the malignant cells, providing the largest
      proportion of energy needed for cell proliferation. Lactate dehydrogenase (LDH)
      catalyses the reversible process of pyruvate to lactate in anaerobic condition.
      LDHA isoenzyme expressed mainly by malignant cells, significantly increases
      lactate formation. Lactate induces the proliferation of oxygenated malignant
      cells, angiogenesis, and inhibits the innate and adaptive immune responses.
      Baseline serum LDH elevation correlates with shorter survival. The authors review
      the relevant studies exploring the correlation between LDH elevation and the
      prognosis of malignant diseases. Orv Hetil. 2017; 158(50): 1977-1988.

PMID- 29226714
TI  - [Analysis of D-dimer laboratory findings and clinical evaluation].
AB  - D-dimer is a product of the enzymatic degradation of the fibrinogen-fibrin
      molecule, and its existence is demonstrable in circulation. The test based limits
      may be considered as normal values. It was first thought to be a product of
      coagulation, then a product of lysis. High-concentration D-dimer in blood
      detected in thromboembolic diseases is considered to be of diagnostic value. In
      cases where thromboembolism was ruled out despite elevated titres but heparin
      (LMWH) or CLOPIDOGREL was given as a cautionary measure, we found that D-dimer
      values remained elevated. This finding means that in vivo coagulation is not a
      precondition to D-dimer formation. Analysis of such cases uncovers liver or
      kidney disease in the background, but old age may also be a factor. Often
      elevated ferritin levels were observed 'in parallel' with elevated D-dimer
      values. These findings lead us to presume an enzymatic degradation process of
      'elderly' protein molecules, which is universally applicable. Orv Hetil. 2017;
      158(50): 1971-1976.

PMID- 29226710
TI  - Group A Streptococcus encounters with host macrophages.
AB  - Group A Streptococcus (GAS) is a leading human bacterial pathogen with diverse
      clinical manifestations. Macrophages constitute a critical first line of host
      defense against GAS infection, using numerous surface and intracellular receptors
      such as Toll-like receptors and inflammasomes for pathogen recognition and
      activation of inflammatory signaling pathways. Depending on the intensity of the
      GAS infection, activation of these signaling cascades may provide a beneficial
      early alarm for effective immune clearance, or conversely, may cause
      hyperinflammation and tissue injury during severe invasive infection. Although
      traditionally considered an extracellular pathogen, GAS can invade and replicate
      within macrophages using specific molecular mechanisms to resist phagolysosomal
      and xenophagic killing. Unraveling GAS-macrophage encounters may reveal new
      treatment options for this leading agent of infection-associated mortality.
      [Formula: see text].

PMID- 29226715
TI  - [Professor George Szemere (1931-2016) founder of the first regional genetic
      counselling service in Hungary].

PMID- 29226716
TI  - [Case report on choroidal effusion after oral acetazolamide administration: an
      unusual manifestation of a well-known idiosyncratic effect?]
AB  - Sulpha drugs are widely employed in medicine for various diseases and disorders.
      During the last several decades, numerous papers had been published on supra
      ciliary and posterior choroidal effusion likely presenting as an idiosyncratic
      effect of these drugs especially of acetazolamide. In each publication, the
      effusion was associated with either an acute angle-closure glaucoma or transitory
      myopia or both of these as leading symptoms. In the current publication, authors
      report on two cases where the acetazolamide-induced choroidal effusion was an
      accidental finding without either a myopic shift in refraction or an acute
      elevation in intraocular pressure. To our best knowledge, ours is the first
      report in the literature describing this unusual, "silent" form of a sulpha drug
      induced choroidal effusion. Since the choroidal involvement may vary in size and
      location, and is not necessarily associated with acute glaucoma and myopia, one
      can assume that a considerable amount of acetazolamide-related ocular side
      effects will not be discovered. The above case report aims to draw the attention
      of other specialities to the need for ophthalmic examination for their patients
      taking sulpha drugs with acute visual deterioration. Orv Hetil. 2017; 158(50):
      1998-2002.

PMID- 29226717
TI  - Atypical chronic myeloid leukemia: a rare entity with management challenges.
AB  - The aim of our study was to review the clinicopathologic features and management
      of atypical chronic myeloid leukemia (aCML). Relevant manuscripts published in
      English were searched using PubMed. aCML is diagnosed as per WHO 2016
      classification in the presence of leukocytosis >=13 * 109/l with circulating
      neutrophil precursors >=10%, monocytes less than 10%, minimal basophils,
      hypercellular bone marrow with granulocytic proliferation and dysplasia, bone
      marrow blast less than 20% and absence of BCR/ABL fusion gene. Common cytogenetic
      features and mutations include trisomy 8, and mutations in SETBP1 and ETNK1.
      Median survival is 1-2 years. Hematopoietic stem cell transplant may be the only
      curative option. Ruxolitinib and dasatinib are emerging therapeutic options.
      Thus, aCML is a rare entity with poor survival. Novel therapies are needed.

PMID- 29226718
TI  - Contribution to FE modeling for intraoperative pedicle screw strength prediction.
AB  - Although the use of pedicle screws is considered safe, mechanical issues still
      often occur. Commonly reported issues are screw loosening, screw bending and
      screw fracture. The aim of this study was to develop a Finite Element (FE) model
      for the study of pedicle screw biomechanics and for the prediction of the
      intraoperative pullout strength. The model includes both a parameterized screw
      model and a patient-specific vertebra model. Pullout experiments were performed
      on 30 human cadaveric vertebrae from ten donors. The experimental force
      displacement data served to evaluate the FE model performance. MUCT images were
      taken before and after screw insertion, allowing the creation of an accurate 3D
      model and a precise representation of the mechanical properties of the bone. The
      experimental results revealed a significant positive correlation between bone
      mineral density (BMD) and pullout strength (Spearman rho = 0.59, p < 0.001) as
      well as between BMD and pullout stiffness (Spearman rho = 0.59, p < 0.001). A
      high positive correlation was also found between the pullout strength and
      stiffness (Spearman rho = 0.84, p < 0.0001). The FE model was able to reproduce
      the linear part of the experimental force-displacement curve. Moreover, a high
      positive correlation was found between numerical and experimental pullout
      stiffness (Pearson rho = 0.96, p < 0.005) and strength (Pearson rho = 0.90, p <
      0.05). Once fully validated, this model opens the way for a detailed study of
      pedicle screw biomechanics and for future adjustments of the screw design.

PMID- 29226719
TI  - Genotoxicity in Brazilian coal miners and its associated factors.
AB  - The present study aims to evaluate the potential genotoxic and associated factors
      among coal miners, divided by degree of exposure. Blood and buccal smears were
      collected from 158 workers, who actively participate in different activities in
      coal mining, and 48 individuals living in the same city but do not have
      participation in coal mining activities (control group). The workers were divided
      into three different groups, according to the level of contact with coal
      extraction. A questionnaire intended to identify factors associated with DNA
      damage was performed in participants. The results regarding oral mucosa
      micronucleus test showed a significant difference ( p < 0.001) of the worker
      groups 1 and 2 in relation to the control group, where the group 1 has a higher
      degree of exposure to coal than group 2. For the lymphocyte micronucleus test and
      comet assay, there was no significant difference between the exposed groups and
      control group. There is an association between the outcome and the fact of living
      in the municipality of the mining company and the exposure to radiation in the
      last 12 months. Besides, the multivariate analysis showed an association of the
      tail moment with radiation exposure in the last 12 months. Thus, the findings of
      this study reveal genotoxicity in oral mucosa cells of workers exposed to coal
      and that workers with higher degree of contact with coal have a more pronounced
      response.

PMID- 29226720
TI  - Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate
      cancer cells.
AB  - Deregulated cancer cell metabolism plays an important role in cancer progression.
      Cancer cell metabolism has been in the centre of attention in therapeutical
      cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin,
      have been studied extensively as preventive and therapeutic agents. Metformin is
      Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other
      chemotherapeutic agents that were shown to have anticancer effects. Memantine is
      an FDA-approved Alzheimer's drug. Drug repositioning studies offer wide range of
      benefits, such as reduced time, cost and risk over de novo drug discovery.
      Therefore, we aimed to target glucose and glutamine metabolism in androgen
      dependent LNCaP cells by using metformin and memantine and investigate these
      agents' effects on prostate cancer cell proliferation in vitro. We evaluated the
      effects of metformin and memantine on the protein expression levels of genes that
      play significant roles in apoptosis and cell cycle progression (Casp3, Casp9, Bcl
      2, Survivin, Bax, c-Myc, HIF1A, CCND1, CDK4 and GAPDH) by Western blotting.
      Alzheimer's drug memantine exerted cytotoxic effects at 0.25 mM and metformin at
      2.5 mM. We identified for the first time that memantine exerts antineoplastic
      activity (0.25 mM) by triggering Bax-dependent pathway of apoptosis. In addition
      to that both molecules have shown similar patterns on pro- and anti-apoptotic
      protein expression levels, such as Bcl-2, Casp3, Survivin and Bax. Our preclinic
      results indicate that memantine might be used as a new repositioned drug in
      cancer treatment. Beyond targeting glucose metabolism, glutamine metabolism also
      holds great promise for a potential treatment option.

PMID- 29226721
TI  - Investigational drugs in phase I and phase II clinical trials for hereditary
      angioedema.
AB  - INTRODUCTION: Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH
      HAE) is a rare bradykinin-mediated disease characterized by recurrent
      subcutaneous and/or submucosal angioedematous attacks (HAE attacks), which occur
      unpredictably. The recurrent HAE attacks do not respond to conventional
      treatments, and may evolve into a life-threatening condition; therefore, special
      therapy is required. Areas covered: The agents used so far for the acute
      management of HAE attacks act by blocking the release of bradykinin, or its
      binding to its receptor. By contrast, the investigational medicinal products
      under evaluation in Phase I and II clinical trials are targeted at the prevention
      of HAE attacks. Chemically, these new drugs are small synthetic molecules,
      oligonucleotides, or antibodies, which inhibit either kallikrein, or Factor XII.
      Expert opinion: The key considerations for the development of new medicinal
      products include more straightforward dosing, self-administration, longer
      duration of action, and keeping the patient attack-free. This review summarizes
      the status and the findings of the currently ongoing Phase I and Phase II
      clinical trials of C1-INH-HAE.

PMID- 29226722
TI  - The use of databases, data mining and immunoinformatics in vaccinology: where are
      we?
AB  - INTRODUCTION: Vaccinology has evolved from a sub-discipline focussed on
      simplistic vaccine development based on antibody-mediated protection to a
      separate discipline involving epidemiology, host and pathogen biology,
      immunology, genomics, proteomics, structure biology, protein engineering,
      chemical biology, and delivery systems. Data mining in combination with
      bioinformatics has provided a scaffold linking all these disciplines to the
      design of vaccines and vaccine adjuvants. Areas covered: This review provides
      background knowledge on immunological aspects which have been exploited with
      informatics for the in silico analysis of immune responses and the design of
      vaccine antigens. Furthermore, the article presents various databases and
      bioinformatics tools, and discusses B and T cell epitope predictions, antigen
      design, adjuvant research and systems immunology, highlighting some important
      examples, and challenges for the future. Expert opinion: Informatics and data
      mining have not only reduced the time required for experimental immunology, but
      also contributed to the identification and design of novel vaccine candidates and
      the determination of biomarkers and pathways of vaccine response. However, more
      experimental data is required for benchmarking immunoinformatic tools.
      Nevertheless, developments in immunoinformatics and reverse vaccinology, which
      are nascent fields, are likely to hasten vaccine discovery, although the path to
      regulatory approval is likely to remain a necessary impediment.

PMID- 29226723
TI  - Pen devices for self-injection: contrasting measured injection force with users'
      perceived ease of injection.
AB  - OBJECTIVES: Past research has emphasized injection force as a clinically highly
      relevant technical attribute of pen devices. However, little work has been
      conducted to relate these results to in-use studies. This article explores
      whether and how differences in pen injection force profiles influence users' self
      reported perceived ease of injection and preferences. METHODS: Three different
      pen systems were subjected to measurements of injection force using an automated
      mechanical set-up followed by a simulated use study where users assessed
      perceived ease of injection. MAIN OUTCOMES MEASURE: Outcomes were measured by
      fitting data of measured injection force and perceived ease of injection using a
      linear model. RESULTS: Although mechanical testing revealed significant
      differences between the three pen's measured injection forces these differences
      were not directly perceived by users in simulated injection studies. CONCLUSION:
      The article bridges literature on injection force measurement and simulated use.
      It reveals how users' perceived ease of injection is less sensitive to measured
      injection forces than prior research has assumed. Thus, future research should
      holistically integrate patient feedback in new device development. Key
      limitations of this work are the low number of participants in the simulated use
      study and the fact that the ease of injection was assessed indirectly.

PMID- 29226724
TI  - Standardization of clinical enzyme analysis using frozen human serum pools with
      values assigned by the International Federation of Clinical Chemistry and
      Laboratory Medicine reference measurement procedures.
AB  - Variation in clinical enzyme analysis, particularly across different measuring
      systems and laboratories, represents a critical but long-lasting problem in
      diagnosis. Calibrators with traceability and commutability are imminently needed
      to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were
      assigned values for alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate
      dehydrogenase (LDH) by six laboratories with established International Federation
      of Clinical Chemistry and Laboratory Medicine reference measurement procedures.
      These serum pools were then used across 76 laboratories as a calibrator in the
      analysis of five enzymes. Bias and imprecision in the measurement of the five
      enzymes tested were significantly reduced by using the value-assigned serum in
      analytical systems with open and single-point calibration. The median
      (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were
      2.0% (0.6-3.4%), 0.8% (-0.8-2.3%), 1.0% (-0.5-2.0%), 0.2% (-0.3-1.0%) and 0.2% (
      0.9-1.1%), respectively. Before calibration, the interlaboratory coefficients of
      variation (CVs) in the analysis of patient serum samples were 8.0-8.2%, 7.3-8.5%,
      8.1-8.7%, 5.1-5.9% and 5.8-6.4% for ALT, AST, GGT, CK and LDH, respectively;
      after calibration, the CVs decreased to 2.7-3.3%, 3.0-3.6%, 1.6-2.1%, 1.8-1.9%
      and 3.3-3.5%, respectively. The results suggest that the use of fresh frozen
      serum pools significantly improved the comparability of test results in
      analytical systems with open and single-point calibration.

PMID- 29226725
TI  - Development of a microcomputed tomography scoring system to characterize disease
      progression in the Hartley guinea pig model of spontaneous osteoarthritis.
AB  - AIM: There is potential discrepancy between human and laboratory animal studies
      of osteoarthritis (OA), as radiographic assessment is the hallmark of the former
      and histopathology the standard for the latter. This suggests a need to evaluate
      OA in animal models in a manner similar to that utilized in people. Our study
      aimed to develop a whole joint grading scheme for microcomputed tomography
      (microCT) images in Hartley guinea pigs, a strain that recapitulates joint
      changes highlighted in human spontaneous OA. MATERIALS AND METHODS: Knees from
      animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and
      standard histologic scoring. Quantitative microCT parameters, such as bone
      volume/total volume were also collected. RESULTS: Both whole joint microCT and
      histologic scores increased with advancing age and showed strong correlation (r =
      0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased
      progressively with age. Whole joint microCT scores, which characterize bony
      changes, followed a stepwise pattern: scores increased between 3 and 5 months of
      age, stayed consistent between 5 and 9 months, and worsened again between 9 and
      15 months. CONCLUSIONS: This work provides data that advocates the use of a whole
      joint microCT scoring system in guinea pig studies of OA, as it provides
      important information regarding bony changes that occur at a different rate than
      articular cartilage changes. This grading scheme, in conjunction with histology
      and quantitative microCT measurements, may enhance the translational value of
      this animal model as it pertains to human work.

PMID- 29226726
TI  - Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental
      application.
AB  - The current study aimed to investigate the effectiveness of a developed sodium
      alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co
      delivery of ketorolac and lidocaine to soft tissues for healing and pain control
      following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were
      formulated and assessed for their hydration capacity, mucoadhesion ability and in
      vitro release profile to select the optimum system for further clinical
      investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10%
      glycerol showed optimum properties and was selected for the clinical study.
      Twenty patients were included in the study and the ketorolac/lidocaine wafer was
      assessed versus a market product. Visual pain analog was evaluated daily for the
      first week and wound healing index was evaluated for one week, two weeks and one
      month following the procedure. The developed ketorolac/lidocaine polymeric wafer
      proved to be an effective method of reducing pain and discomfort together with
      enhancing wound healing following gingivectomy.

PMID- 29226727
TI  - High expression of interleukine-1 receptor antagonist in rheumatoid arthritis:
      Association with IL1RN*2/2 genotype.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation
      and pro-inflammatory cytokines production. IL-1Ra is an anti-inflammatory
      cytokine codified by IL1RN gene that blocks IL-1 signalling. A VNTR polymorphism
      of 86 bp in IL1RN gene has been associated with RA risk and regulation of IL-1Ra
      expression. In this study, we determined mRNA and protein expression of IL-1Ra in
      RA patients and control subjects (CS). This study included 85 RA patients
      classified according to the ACR/EULAR 2010 criteria and 67 CS. Polymerase chain
      reaction was used to identify IL1RN VNTR polymorphism, the expression of sIL-1Ra
      (secreted isoform) mRNA was determined by SYBR Green-based real time quantitave
      PCR assay, and IL-1Ra soluble levels quantification was evaluated by ELISA test.
      RA patients had higher soluble levels of IL-1Ra than CS (p < .01), sIL-1Ra mRNA
      expression was higher in RA patients compared to CS (p < .01). Carriers of
      IL1RN*2/2 homozygous genotype show increased IL-1Ra soluble levels compared to
      IL1RN*long/long and IL1RN*2/long genotypes (p < .05) in the CS group, whereas
      mRNA expression in carriers of IL1RN*2/2 genotype was 1.2 times higher compared
      to IL1RN*long/long genotypes in the same group. Regarding RA patients, high
      expression of sIL-1Ra mRNA on carriers of IL1RN*long/long genotype was observed.
      Nevertheless, in RA patients IL-1Ra soluble levels among genotypes did not show
      significant differences. High expression of IL-1Ra in RA patients under treatment
      or not with antirheumatic drugs was detected. Additionally, carriers of IL1RN*2/2
      genotype had higher IL-1Ra expression than carriers of other genotypes.

PMID- 29226728
TI  - The efficacy and safety of riluzole for neurodegenerative movement disorders: a
      systematic review with meta-analysis.
AB  - Neurodegenerative movement disorders mainly include Parkinson's disease, atypical
      parkinsonisms, Huntington disease, and hereditary ataxia. Riluzole is the only
      drug approved by the US Food and Drug Administration for amyotrophic lateral
      sclerosis. The neuroprotective effects of riluzole have been observed in
      experimental models of neurodegenerative movement disorders. In this paper, we
      aimed to systematically analyze the efficacy and safety of riluzole for patients
      with neurodegenerative movement disorder. We searched the electronic databases
      such as PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge
      Infrastructure until June 2017 for the eligible randomized controlled trials, as
      well as the unpublished and ongoing trials. For continuous data, we calculated
      standardized mean differences with 95% confidence intervals if studies did not
      use the same scales to measure outcomes. For dichotomous data, we calculated risk
      differences if a trial reported no adverse events or dropouts. We pooled the
      results using a random-effects model. We included nine studies with 1320 patients
      with neurodegenerative movement disorders, which compared riluzole with placebo.
      No significant difference was found in the number of participants with adverse
      events but with motor improvement in hereditary ataxia. There were only two
      studies focusing on neuroprotective effect. Riluzole is well-tolerated in the
      patients with neurodegenerative movement disorders. Riluzole seems to be
      promising for patients with hereditary ataxia in symptomatic effect, which needs
      to be further confirmed by well-designed studies in the future. Moreover, it
      makes sense to design long-term study focusing on neuroprotective effect of
      riluzole in disease-modifying.

PMID- 29226730
TI  - Correction to: Silver nanoparticle exposure in pregnant rats increases gene
      expression of tyrosine hydroxylase and monoamine oxidase in offspring brain.

PMID- 29226729
TI  - Formulation of sitagliptin-loaded oral polymeric nano scaffold: process
      parameters evaluation and enhanced anti-diabetic performance.
AB  - PURPOSE: The aim of the study to formulate and statistically optimize sitagliptin
      loaded eudragit nanoparticles (SIT-NPs) and evaluate the in-vitro pharmaceutical
      quality and in-vivo anti-diabetic assessment. METHOD: SIT-NPs were prepared by
      using combination method of solvent evaporation and nano-precipitation
      techniques. The influence of different independent variables as eudragit RL100
      concentration (%), tween 80 concentration (%) and sonication time (min) were
      evaluated on dependent variables like particle size (nm), drug loading (%) and in
      vitro drug release (%). Further, the optimized formulation was evaluated for
      surface morphology, CLSM, ex-vivo permeation study and in-vivo anti-diabetic
      activity and stability study. RESULTS: The developed SIT-NPs formulations showed
      particle size range (135.86-193.45 nm), drug loading (6.36-8.76%) and prolonged
      drug release over 24 h. The prepared SIT-NPs were found to be nearly spherical
      with smooth surface. The comparative in-vitro release study and CLSM study
      results revealed that SIT-NPopt showed significantly (p < .05) enhanced release
      and permeation as compared to SIT free solution (SIT-Fs). The in-vivo anti
      diabetic assessment revealed that SIT-NPopt able to reduce the blood sugar level
      (BSL) for a prolonged period of time. Further, the stability study data showed
      the formulations were found stable at both temperature and having the shelf life
      of 488 d. CONCLUSIONS: This research has shown that SIT-NPs based on experimental
      design offers a new and better approach to delivering SIT, thus encouraging
      further development of this formulation.

PMID- 29226731
TI  - Pharmacogenetics of platinum-based chemotherapy in non-small cell lung cancer:
      predictive validity of polymorphisms of ERCC1.
AB  - INTRODUCTION: The efficacy of platinum-based chemotherapy for patients with non
      small cell lung cancer (NSCLC) is limited by chemoresistance. Platinum drugs
      damage DNA by introducing intrastrand and interstrand crosslinks which result in
      cell death. Excision repair cross-complementing 1 (ERCC1) is a member of the
      nucleotide excision repair (NER) pathway which erases such defects. Single
      nucleotide polymorphisms (SNPs) in ERCC1 impair this activity and have been
      suggested to predict the response to chemotherapy. Area covered: Among the
      polymorphisms of proteins involved in uptake, metabolism, cytotoxicity and efflux
      of platinum drugs, codon 118 C/T and C8092A in ERCC1 are the best characterized
      SNPs studied for their predictive power. Here, the divergent results for studies
      of these markers in NSCLC are summarized and the reasons for this contradictory
      data discussed. Expert opinion: Cytotoxicity of platinum compounds comprise
      complex cellular processes for which DNA repair may not constitute the rate
      limiting step. These drugs are administered as doublets to histologically diverse
      patients and, furthermore, the NER pathway in ERCC1 wildtype cohorts may be still
      impaired by the chemotherapeutics applied. At present, assessment of a limited
      number of polymorphism in DNA repair proteins is not reliably associated with
      response to treatment in NSCLC patients.

PMID- 29226732
TI  - Pharmacokinetics and pharmacogenetics of anti-tubercular drugs: a tool for
      treatment optimization?
AB  - INTRODUCTION: WHO global strategy is to end tuberculosis epidemic by 2035.
      Pharmacokinetic and pharmacogenetic studies are increasingly performed and might
      confirm their potential role in optimizing treatment outcome in specific settings
      and populations. Insufficient drug exposure seems to be a relevant factor in
      tuberculosis outcome and for the risk of phenotypic resistance. Areas covered:
      This review discusses available pharmacokinetic and pharmacogenetic data of first
      and second-line antitubercular agents in relation to efficacy and toxicity.
      Pharmacodynamic implications of optimized drugs and new options regimens are
      reviewed. Moreover a specific session describes innovative investigations on drug
      penetration. Expert opinion: The optimal use of available antitubercular drugs is
      paramount for tuberculosis control and eradication. Whilst trials are still on
      going, higher rifampicin doses should be reserved to treatment for tubercular
      meningitis. Therapeutic Drug Monitoring with limiting sampling strategies is
      advised in patients at risk of failure or with slow treatment response. Further
      studies are needed in order to provide definitive recommendations of
      pharmacogenetic-based individualization: however lower isoniazid doses in NAT2
      slow acetylators and higher rifampicin doses in individuals with SLCO1B1 loss of
      function genes are promising strategies. Finally in order to inform tailored
      strategies we need more data on tissue drug penetration and pharmacological
      modelling.

PMID- 29226733
TI  - Enteric-coated insulin microparticles delivered by lipopeptides of iturin and
      surfactin.
AB  - Surfactin, a lipopeptide produced by Bacillus species, has been used for the oral
      delivery of insulin. In this study, another lipopeptide of iturin was tested for
      its ability to orally delivery insulin alone or plus surfactin. Iturin could form
      co-precipitate with insulin at acidic pH values. After treatment by
      ultrasonification, the structure of coprecipitate was destroyed that led to a
      significant decrease in hypoglycemic effect after oral administration. Iturin
      weakly binds to (Kd = 257 MUM) and induce insulin structure more compact that is
      favorable for insulin uptake by the intestine. After being coated with Acryl-Eze
      by lyophilization, the coprecipitate formed the spherical enteric-coated insulin
      microparticles delivered by iturin with a relative oral bioavailability of 6.84%
      in diabetic mice. For further improving oral hypoglycemic effect, surfactin was
      added to form the spherical enteric-coated insulin microparticles in a
      formulation containing insulin, Acryl-Eze, iturin and surfactin at a ratio of
      1:1:0.5: 0.5 (w/w), with an insulin encapsulation efficiency of 66.22%. The
      enteric-coated insulin microparticles delivered by iturin plus surfactin showed a
      classical profile for controlled release in the intestine with a relative
      bioavailability of 7.67% after oral administration, which could effectively
      control the postprandial blood glucose at a level about 50% of the initial one
      just like the subcutaneous injection. Collectively, iturin plus surfactin is more
      efficient for oral delivering insulin than the sole one, and the resultant
      enteric-coated insulin microparticles are potential for the development of oral
      insulin to control postprandial blood glucose in diabetic patients.

PMID- 29226734
TI  - Emerging first line treatment options for bladder cancer: a review of phase II
      and III therapies in the pipeline.
AB  - INTRODUCTION: The treatment of urothelial carcinoma (UC) had remained unchanged
      for several years until the recent FDA approval of immune checkpoint inhibitors
      (CPIs) in the salvage setting. Novel dual CPI-CPI and CPI-chemotherapy
      combinations are now being investigated aggressively as first line therapy for
      metastatic disease. Areas covered: We discuss the recent insights into the tumor
      biology of UC, which may impact the prognosis as well as assist in developing
      precision medicine. This is followed by an overview of existing treatment
      including conventional chemotherapy as well as the trials that led to the recent
      approval of PD-1 and PD-L1 inhibitors. Ongoing phase II and phase III trials
      developing PD-1/PD-L1 inhibitors, CTLA-4 inhibitors and VEGF inhibitors as first
      line therapy are discussed. Expert opinion: The treatment paradigm for the first
      line therapy of UC is expected to shift from conventional platinum-based
      combination chemotherapy towards novel therapy incorporating CPI immunotherapy.
      Finding the right combination of drugs in the appropriate disease setting and
      identifying the right patient population based on biomarkers are important
      questions to be answered. Another major challenge will be the financial burden
      associated with these new drugs.

PMID- 29226735
TI  - Social media for health promotion: What messages are women receiving about
      cardiovascular disease risk by the Canadian Heart and Stroke Foundation?
AB  - The aim of this study was to explore the meanings of women's cardiovascular
      disease constructed within the Canadian Heart and Stroke Foundation Facebook
      page. Posts from Heart and Stroke Foundation and public user comments surrounding
      the launch of the Heart and Stroke Foundation re-branding were of interest.
      Ethnographic content analysis was employed to analyse text ( n = 40), images ( n
      = 32), videos ( n = 6), user comments and replies ( n = 42) from November 2016 to
      March 2017. Constructions (re)presented on Facebook of 'typical' women at risk
      and risk reduction were problematic as women most at risk were excluded through
      the use of consumerist, medicalized identities which also excluded promotion of
      healthy behaviour changes.

PMID- 29226736
TI  - The effect of major adverse renal cardiovascular event (MARCE) incidence,
      procedure volume, and unit cost on the hospital savings resulting from contrast
      media use in inpatient angioplasty.
AB  - OBJECTIVE: To determine the net economic impact of switching from low-osmolar
      contrast media (LOCM) to iso-osmolar contrast media (IOCM; iodixanol) in patients
      undergoing inpatient coronary or peripheral angioplasty in the United States
      (US). METHODS: A budget impact model (BIM) was developed from a hospital
      perspective. Nationally representative procedural and contrast media prevalence
      rates, along with MARCE (major adverse renal cardiovascular event) incidence and
      episode-related cost data were derived from Premier Hospital Data (October 2014
      to September 2015). A previously estimated relative risk reduction in MARCE
      associated with IOCM usage (9.3%) was applied. The higher cost of IOCM was
      included when calculating the net impact estimates at the aggregate, hospital
      type, and per hospital levels. One-way (+/-25%) and probabilistic sensitivity
      analyses identified the model's most important inputs. RESULTS: Based on weighted
      analysis, 513,882 US inpatient angioplasties and 35,610 MARCE cases were
      estimated annually. Switching to an "IOCM only" strategy from a "LOCM only"
      strategy increases contrast media cost, but prevents 2,900 MARCE events. The
      annual budget impact was an estimated saving of $30.71 million, aggregated across
      all US hospitals, $6,316 per hospital, or $60 per procedure. Net savings were
      maintained across all univariate sensitivity analyses. While MARCE/event-free
      cost differential was the most important factor driving total net savings for
      hospitals in the Northeast and West, procedural volume was important in the
      Midwest and rural locations. CONCLUSIONS: Switching to an "IOCM only" strategy
      from a "LOCM only" approach yields substantial net global savings to hospitals,
      both at the national level and within hospital sub-groups. Hospital
      administrators should maintain awareness of the factors that are likely to be
      more influential for their hospital and recognize that purchasing on the basis of
      lower contrast media cost may result in higher overall costs for patients
      undergoing inpatient angioplasty.

PMID- 29226738
TI  - Erratum.

PMID- 29226737
TI  - Pseudoxanthoma Elasticum-Like in beta-Thalassemia Major, a matter of alpha-Klotho
      and Parathyroid Hormone?
AB  - Pseudoxanthoma elasticum-like (PXL) condition is one of the complications faced
      by patients with beta-thalassemia major (beta-TM). Histopathological features
      include abnormal, mineralized and fragmented elastic fibers in skin, eyes and
      arterial blood vessels (elastorrhexia). The pathogenesis of PXL lesions in beta
      TM is not yet completely understood. This study was aimed at analyzing a possible
      implication of alpha-Klotho in the clinical manifestation of PXL in patients with
      beta-TM (30 with and 78 without PXL). A significant correlation was observed
      between Klotho, parathyroid hormone (PTH) and serum calcium (Ca). Our analysis
      seems to indicate alpha-Klotho and PTH as factors that can affect the development
      of PXL.

PMID- 29226739
TI  - Rutin-phospholipid complex in polymer matrix for long-term delivery of rutin via
      skin for the treatment of inflammatory diseases.
AB  - The drug with poor oral bioavailability necessitates the development of novel
      carrier for efficient drug delivery. This paper reports the rutin-phospholipid
      complex in polymer matrix for sustained delivery of rutin via the skin for the
      treatment of acute and chronic inflammatory diseases. Rutin in phospholipid
      complex (RNPs) are better soluble and permeable than the free rutin. The RNPs
      loaded polymeric matrix patch with moderate adhesiveness was developed for
      convenient means of long term drug application on the skin. The patch was
      analysed for physicochemical properties, ex vivo skin permeability and in vivo
      efficacy in rat paw oedema model. The skin targeting efficacy was analysed by
      CLSM study. Optimized formulation (F2) showed 31 +/- 2.32% and 26.56 +/- 5.52%
      skin permeation at 24 h across excised rat skin and human cadaver skin,
      respectively. The sustained anti-inflammatory effect of the patch formulation in
      rat paw oedema model confirmed its unique in vivo efficacy over the conventional
      diclofenac gel. The CLSM study confirmed the localization of RNPs in the dermis
      for sustained anti-inflammatory effect. Our results suggest that the developed
      patch has a potential for long term site specific delivery of rutin in arthritic
      patients.

PMID- 29226740
TI  - Do infants in the neonatal intensive care unit diagnosed with urinary tract
      infection need a routine voiding cystourethrogram?
AB  - OBJECTIVE: To determine if infants diagnosed with urinary tract infection (UTI)
      in the neonatal intensive care unit (NICU) require a routine voiding
      cystourethrogram (VCUG). STUDY DESIGN: Retrospective data analysis from three
      centers for infants admitted to the NICU born between 2000 and 2013 and diagnosed
      with UTI. RESULTS: One hundred twenty-six infants from three centers were
      diagnosed with UTI during their hospitalization. Renal ultrasound (RUS) was
      performed in 115 infants (91.2%), of which 69 (60%) were abnormal. Mild to
      moderate hydronephrosis or pelviectasis were the most common abnormalities
      identified (n = 34, 30%). There were 14 infants (12%) with severe abnormalities
      on RUS. VCUG was performed in 71 infants (56%), of which 3 (4%) were interpreted
      as abnormal with grade 2 vesicoureteral reflux (VUR) or less (two infants were
      with normal RUS and one infant was with abnormal RUS). CONCLUSIONS: More than 50%
      of infants with a UTI had an abnormal RUS but severe abnormalities were found
      only in 11% of infants. Only 4% of infants with UTI had VUR; none of these
      infants had severe VUR on VCUG. A routine VCUG after UTI in the NICU has a low
      yield and may be reserved for infants with severe or persistent abnormalities on
      RUS.

PMID- 29226741
TI  - Side effects associated with current and prospective antimigraine
      pharmacotherapies.
AB  - INTRODUCTION: Migraine is a neurovascular disorder. Current acute specific
      antimigraine pharmacotherapies target trigeminovascular 5-HT1B/1D, 5-HT1F and
      CGRP receptors but, unfortunately, they induce some cardiovascular and central
      side effects that lead to poor treatment adherence/compliance. Therefore, new
      antimigraine drugs are being explored. Areas covered: This review considers the
      adverse (or potential) side effects produced by current and prospective
      antimigraine drugs, including medication overuse headache (MOH) produced by
      ergots and triptans, the side effects observed in clinical trials for the new
      gepants and CGRP antibodies, and a section discussing the potential effects
      resulting from disruption of the cardiovascular CGRPergic neurotransmission.
      Expert opinion: The last decades have witnessed remarkable developments in
      antimigraine therapy, which includes acute (e.g. triptans) and prophylactic (e.g.
      beta-adrenoceptor blockers) antimigraine drugs. Indeed, the triptans represent a
      considerable advance, but their side effects (including nausea, dizziness and
      coronary vasoconstriction) preclude some patients from using triptans. This has
      led to the development of the ditans (5-HT1F receptor agonists), the gepants
      (CGRP receptor antagonists) and the monoclonal antibodies against CGRP or its
      receptor. The latter drugs represent a new hope in the antimigraine
      armamentarium, but as CGRP plays a role in cardiovascular homeostasis, the
      potential for adverse cardiovascular side effects remains latent.

PMID- 29226742
TI  - Early results of a phase-II study of modified short-course radiotherapy combined
      with capecitabine and delayed surgery for T3M0 lower rectal cancer.

PMID- 29226743
TI  - Molecular docking and molecular dynamics simulations of fumarate hydratase and
      its mutant H235N complexed with pyromellitic acid and citrate.
AB  - Fumarase catalyzes the reversible, stereospecific hydration/dehydration of
      fumarate to L-malate during the Kreb's cycle. In the crystal structure of the
      tetrameric fumarase, it was found that some of the active site residues S145,
      T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with
      pyromellitic acid and citrate which help to the protonation state for the
      conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water
      mediated interactions were lost due to the shifting of active site water molecule
      by 0.7 A away. Molecular dynamics (MD) simulations were also carried out by NAMD
      and analyzed using Assisted Model Building with Energy Refinement (AMBER) program
      to better understand the conformational stability and other aspects during the
      binding of pyromellitic acid and citrate with native and mutant FH. The role of
      hydrogen bonds and hydrophobic interactions was also analyzed. The present study
      confirms that the H235N mutation has a major effect on the catalytic activity of
      fumarase which is evident from the biochemical studies.

PMID- 29226744
TI  - The role of adjuvant chemotherapy in locally advanced bladder cancer.
AB  - PURPOSE: The standard of care for locally advanced bladder cancer (LABC) is
      neoadjuvant chemotherapy followed by cystectomy. However, the role of adjuvant
      therapy is unclear. The purpose of this study was to evaluate the outcomes of
      adjuvant chemotherapy for patients with LABC following neoadjuvant chemotherapy
      and cystectomy, and to determine whether select patients may benefit from
      adjuvant chemotherapy. METHODS: The National Cancer Data Base (NCDB) was queried
      (2004-2013) for patients with newly diagnosed pT3-4N0-3M0 bladder cancer that
      received neoadjuvant chemotherapy and cystectomy. Patients were divided into two
      groups based on the adjuvant therapy they received: chemotherapy alone or
      observation. Statistics included multivariable logistic regression to determine
      factors predictive of receiving adjuvant chemotherapy, Kaplan-Meier analysis to
      evaluate overall survival (OS) and Cox proportional hazards modeling to determine
      variables associated with OS. RESULTS: Altogether, 2592 patients met inclusion
      criteria; 901 (34.8%) patients received adjuvant chemotherapy, while 1691 (65.2%)
      were observed. Patients treated with adjuvant chemotherapy were more likely to
      have positive margins were younger and more likely to receive treatment at a
      nonacademic facility. There was no difference in median OS between patients
      treated with or without adjuvant chemotherapy (22.6 vs. 21.1 months; p = .267).
      However, a longer median OS was observed with the use of adjuvant chemotherapy
      was observed among patients with N2-3 disease (17.5 vs. 14.4 months; p = .005)
      and positive surgical margins (16.7 vs. 12.2 months; p = .025). On multivariate
      analysis, advancing age, pT4 stage, positive N stage, positive margins and lower
      socioeconomic status were associated with worse OS. CONCLUSIONS: In the largest
      study to date evaluating efficacy of adjuvant chemotherapy, while no difference
      in OS was observed for adjuvant chemotherapy in all patients, a longer OS was
      observed among patients with N2-3 disease or with positive surgical margins.
      Prospective studies are recommended to further evaluate these findings.

PMID- 29226746
TI  - What Can IRBs Learn From CABs? A Qualitative Analysis of the Experiences of
      Recruitment and Training of Nonscientist Members on Research Review Boards.
AB  - Governments, funders, and institutional policies increasingly encourage and even
      mandate the involvement of nonscientists in the ethical review of research, most
      famously in institutional review boards (IRBs), but also on community advisory
      boards (CABs) and other committees that contribute to research governance. In
      spite of these requirements, few have examined how different factors such as
      recruitment strategies, training, and different qualifications shape the
      contributions of nonscientists to the research enterprise. This pilot study
      begins to fill in this lacuna by interviewing nonscientist members of IRBs and
      community members of CABs. Results suggest patterned differences in demographics,
      recruitment strategies, training, and perceived qualifications between community
      members on these two types of boards with potential implications for how we
      perceive the scope of contributions that nonscientists can provide to the ethical
      review of research and the strategic ways these contributions can be elicited.

PMID- 29226745
TI  - Management of Adolescent-Parent Dyads' Discordance for Willingness to Participate
      in a Reproductive Health Clinical Trial.
AB  - The objective of this study is to understand the resolution of discordance
      between adolescent-parent dyads about participation in research. Adolescent (14
      17 years) and parent dyads were recruited from NYC pediatric clinics to assess
      attitudes toward research participation. A subset of dyads participated in
      videotaped discussions about participation in a hypothetical study. Videos from
      dyads that held strongly discordant opinions about participation ( n = 30) were
      content-coded and analyzed using a thematic framework approach. Strategies used
      to resolve discordance included asserting authority, granting autonomy, or
      recognizing inaccurate assumptions using a variety of communication behaviors.
      Missed opportunities to enroll initially discordant dyads may be avoided by
      allowing time for adolescents and parents to elicit information, clarify a
      situation, or convince the other.

PMID- 29226747
TI  - Examining Data Repository Guidelines for Qualitative Data Sharing.
AB  - Qualitative data provide rich information on research questions in diverse
      fields. Recent calls for increased transparency and openness in research
      emphasize data sharing. However, qualitative data sharing has yet to become the
      norm internationally and is particularly uncommon in the United States. Guidance
      for archiving and secondary use of qualitative data is required for progress in
      this regard. In this study, we review the benefits and concerns associated with
      qualitative data sharing and then describe the results of a content analysis of
      guidelines from international repositories that archive qualitative data. A
      minority of repositories provide qualitative data sharing guidelines. Of the
      guidelines available, there is substantial variation in whether specific topics
      are addressed. Some topics, such as removing direct identifiers, are consistently
      addressed, while others, such as providing an anonymization log, are not. We
      discuss the implications of our study for education, best practices, and future
      research.

PMID- 29226749
TI  - Is ginger really effective for the treatment of the first trimester nausea and
      vomiting?

PMID- 29226748
TI  - Epigenetic biomarkers: Current strategies and future challenges for their use in
      the clinical laboratory.
AB  - Epigenetic modifications and regulators represent potential molecular elements
      which control relevant physiological and pathological features, thereby
      contributing to the natural history of human disease. These epigenetic modulators
      can be employed as disease biomarkers, since they show several advantages and
      provide information about gene function, thus explaining differences among
      patient endophenotypes. In addition, epigenetic biomarkers can incorporate
      information regarding the effects of the environment and lifestyle on health and
      disease, and monitor the effect of applied therapies. Technologies used to
      analyze these epigenetic biomarkers are constantly improving, becoming much
      easier to use. Laboratory professionals can easily acquire experience and
      techniques are becoming more affordable. A high number of epigenetic biomarker
      candidates are being continuously proposed, making now the moment to adopt
      epigenetics in the clinical laboratory and convert epigenetic marks into reliable
      biomarkers. In this review, we describe some current promising epigenetic
      biomarkers and technologies being applied in clinical practice. Furthermore, we
      will discuss some laboratory strategies and kits to accelerate the adoption of
      epigenetic biomarkers into clinical routine. The likelihood is that over time,
      better markers will be identified and will likely be incorporated into future
      multi-target assays that might help to optimize its application in a clinical
      laboratory. This will improve cost-effectiveness, and consequently encourage the
      development of theragnosis and the application of precision medicine.

PMID- 29226750
TI  - The pronoun distance index.

PMID- 29226752
TI  - Influence of time of delivery on risk of adverse neonatal outcome in different
      size of delivery units: a retrospective cohort study in Finland.
AB  - PURPOSE: To evaluate the impact of time of birth on adverse neonatal outcome in
      singleton term hospital births. MATERIALS AND METHODS: Medical Birth Register
      Data in Finland from 2005 to 2009. Study population was all hospital births (n =
      263,901), excluding multiple pregnancies, preterm births <37 weeks, major
      congenital anomalies or birth defects, and antepartum stillbirths. Main outcome
      measures were either 1-minute Apgar score 0-3, 5-minute Apgar score 0-6, or
      umbilical artery pH <7.00, and intrapartum and early neonatal mortality. We
      calculated risk ratios (ARRs) adjusted for maternal age and parity, and 95%
      confidence intervals (CIs) to indicate the probability of adverse neonatal
      outcome outside of office hours in normal vaginal delivery, in vaginal breech
      delivery, in instrumental vaginal delivery, and in elective and nonelective
      cesarean sections. We analyzed different size-categories of maternity hospitals
      and different on-call arrangements. RESULTS: Instrumental vaginal delivery had
      increased risk for mortality (ARR 3.31, 95%CI; 1.01-10.82) outside office hours.
      Regardless of hospital volume and on-call arrangement, the risk for low Apgar
      score or low umbilical artery pH was higher outside office hours (ARR 1.23,
      95%CI; 1.15-1.30). Intrapartum and early neonatal mortality increased only in
      large, nonuniversity hospitals outside office hours (ARR 1.51, 95%CI; 1.07-2.14).
      CONCLUSIONS: Compared to office hours, babies born outside office hours are in
      higher risk for adverse outcome. Demonstration of more detailed circadian effects
      on adverse neonatal outcomes in different subgroups requires larger data.

PMID- 29226751
TI  - Nordic Cancer Registries - an overview of their procedures and data
      comparability.
AB  - BACKGROUND: The Nordic Cancer Registries are among the oldest population-based
      registries in the world, with more than 60 years of complete coverage of what is
      now a combined population of 26 million. However, despite being the source of a
      substantial number of studies, there is no published paper comparing the
      different registries. Therefore, we did a systematic review to identify
      similarities and dissimilarities of the Nordic Cancer Registries, which could
      possibly explain some of the differences in cancer incidence rates across these
      countries. METHODS: We describe and compare here the core characteristics of each
      of the Nordic Cancer Registries: (i) data sources; (ii) registered disease
      entities and deviations from IARC multiple cancer coding rules; (iii) variables
      and related coding systems. Major changes over time are described and discussed.
      RESULTS: All Nordic Cancer Registries represent a high quality standard in terms
      of completeness and accuracy of the registered data. CONCLUSIONS: Even though the
      information in the Nordic Cancer Registries in general can be considered more
      similar than any other collection of data from five different countries, there
      are numerous differences in registration routines, classification systems and
      inclusion of some tumors. These differences are important to be aware of when
      comparing time trends in the Nordic countries.

PMID- 29226753
TI  - Balint under the microscope: What really happens in Balint groups?

PMID- 29226754
TI  - Cardiac troponins: 25 years on the stage and still improving their clinical
      value.
AB  - Twenty-five years ago, non-isotopic immunoassays for measuring the cardiac
      specific isoforms of troponin I (cTnI) and T (cTnT) were developed. Both
      biomarkers radically changed the diagnosis, prognosis, and therapy indication of
      acute coronary syndromes (ACS) and, particularly, of myocardial infarction (MI).
      However, cardiac troponins (cTn) rapidly demonstrated their usefulness in other
      cardiac and non-cardiac conditions, a part of the ischemic coronary diseases.
      Consequently, the number of patients to be tested for cTn and the number of tests
      requested to clinical laboratories sharply increased. Though the manufacturers
      continuously improved the analytical characteristics of the first cTn assays and
      produced different cTn assay "generations", the universal definition of
      myocardial infarction required less-than-available analytical imprecision at the
      cTn concentration used to assess MI (i.e. the 99th reference percentile). To
      address the clinical requirements, manufacturers developed the high-sensitivity
      cTn (hs-cTn) assays that allow to measure the 99th reference percentile with
      adequate precision, to detect cTn in many healthy subjects and, hence, to
      calculate the hs-cTn biological variation and especially to observe in very short
      time intervals serial differences in hs-cTn attributable to cardiac ischemia.
      Since the number of patients attending the emergency departments (ED) for a
      suspected ACS or MI is increasing, the improved properties of hs-cTn assays,
      allowing faster and safer patient assessment, will help to alleviate the
      sometimes overcrowded EDs. However, there are many biological, analytical, and
      clinical factors that can influence the true hs-cTn values of a patient.
      Clinicians and laboratory professionals should know about them for the best
      interpretation of the otherwise largely useful hs-cTn measurements. In
      conclusion, 25 years after their introduction for clinical use, "cTn are still on
      the stage and improving their clinical value".

PMID- 29226755
TI  - Vaccination Rates in Patients With Medical Indications for the Pneumococcal
      Polysaccharide Vaccine in a Family Medicine Clinic.
AB  - BACKGROUND: Pneumococcal vaccination rates among high-risk patients (eg,
      diabetes, asthma, smoking) seen in 2 family medicine clinics are unknown.
      OBJECTIVES: To assess differences in pneumococcal polysaccharide vaccination
      rates and reasons for nonvaccination among patients with diabetes and asthma and
      patients who smoke. METHODS: A chart review at 2 family medicine residency
      training clinics showed 425 patients with a medical indication for PPSV23 were
      seen between April 1, 2015, and April 30, 2015. One reviewer searched the
      electronic health records to assess reasons for nonvaccination. RESULTS: Rates of
      nonvaccination were 29.8% in patients with diabetes, 58.7% in patients with
      asthma, and 62.5% in patients who smoke cigarettes. Patients were classified into
      3 groups based on the reasons for nonvaccination: documented patient refusal, not
      being addressed by a provider, and being documented as low risk despite the
      presence of a medical indication. CONCLUSION: The 3 reasons for nonvaccination
      were vaccination not being addressed, misclassification of high-risk patients as
      low-risk patients for infection, and documented patient refusal. Providers
      overlooked vaccination more often in patients with asthma and cigarette use than
      in patients with diabetes. Patients seeing pharmacists were most likely to be
      vaccinated, whereas patients seeing physician assistants were least likely to be
      vaccinated. Pharmacists see patients to provide medication management and
      preventive care, whereas other providers treat more urgent conditions. Because
      indications are often overlooked and not addressed, pharmacists can play a larger
      role in identifying and vaccinating high-risk patients.

PMID- 29226757
TI  - Developmental Steps in Metaphorical Language Abilities: The Influence of Age,
      Gender, Cognitive Flexibility, Information Processing Speed, and Analogical
      Reasoning.
AB  - PURPOSE: Metaphor is a specific type of figurative language that is used in
      various important fields such as in the work with children in clinical or
      teaching contexts. The aim of the study was to investigate the developmental
      course, developmental steps, and possible cognitive predictors regarding metaphor
      processing in childhood and early adolescence. METHOD: One hundred sixty-four
      typically developing children (7-year-olds, 9-year-olds) and early adolescents
      (11-year-olds) were tested for metaphor identification, comprehension,
      comprehension quality, and preference by the Metaphoric Triads Task as well as
      for analogical reasoning, information processing speed, cognitive flexibility
      under time pressure, and cognitive flexibility without time pressure. RESULTS:
      Metaphor identification and comprehension consecutively increased with age.
      Eleven-year-olds showed significantly higher metaphor comprehension quality and
      preference scores than seven- and nine-year-olds, whilst these younger age groups
      did not differ. Age, cognitive flexibility under time pressure, information
      processing speed, analogical reasoning, and cognitive flexibility without time
      pressure significantly predicted metaphor comprehension. CONCLUSIONS:
      Metaphorical language ability shows an ongoing development and seemingly changes
      qualitatively at the beginning of early adolescence. These results can possibly
      be explained by a greater synaptic reorganization in early adolescents.
      Furthermore, cognitive flexibility under time pressure and information processing
      speed possibly facilitate the ability to adapt metaphor processing strategies in
      a flexible, quick, and appropriate way.

PMID- 29226756
TI  - Voluntary wheel running improves adipose tissue immunometabolism in
      ovariectomized low-fit rats.
AB  - Loss of ovarian hormones is associated with increased adiposity, white adipose
      tissue (WAT) inflammation, and insulin resistance (IR). Previous work
      demonstrated ovariectomized (OVX) rats bred for high aerobic fitness (HCR) are
      protected against weight gain and IR compared to rats bred for low aerobic
      fitness (LCR) yet wheel running prevents OVX-induced IR in LCR rats. The purpose
      of this study was to determine whether adipose tissue immunometabolic
      characteristics from female HCR and LCR rats differs before or after OVX, and
      whether wheel running mitigates OVX-induced adipose tissue immunometabolic
      changes in LCR rats. Female OVX HCR and LCR rats were all fed a high fat diet
      (HFD) (n = 7-8/group) and randomized to either a running wheel or remain
      sedentary for 11 weeks. Ovary-intact rats (n = 7-12/group) were fed a standard
      chow diet with no wheel. Ovary-intact LCR rats had a greater visceral WAT
      inflammatory profile compared to HCR. Following OVX, sedentary LCR rats had
      greater serum leptin (p<0.001) and WAT inflammation (p<0.05) than sedentary HCR.
      Wheel running normalized the elevated serum leptin and reduced both visceral
      (p<0.05) and subcutaneous (p<0.03) WAT inflammatory markers in the LCR rats.
      Paradoxically, wheel running increased some markers of WAT inflammation in OVX
      HCR rats (p<0.05), which correlated with observed weight gain. Taken together,
      HCR rats appear to have a healthier WAT immune and metabolic profile compared to
      LCR, even following OVX. Wheel running improves WAT health in previously
      sedentary LCR rats. On the other hand, increased WAT inflammation is associated
      with adiposity gain despite a high volume of wheel running in HCR rats.

PMID- 29226758
TI  - Evolution of non-communicable disease prevention and control in China.
AB  - The 70-year experience of China in fighting against non-communicable diseases
      (NCDs) can be classified into three distinct periods: 1) the disease-oriented
      strategy period (from 1950 to 1994); 2) the risk factor-focused strategy period
      (from 1995 to 2008); and 3) the social and policy priority strategy period (since
      2009). A number of projects were successful and valuable experience and lessons
      were accumulated during the three periods. Due to the underestimation of the
      'explosive' epidemic of NCDs, however, it took China quite a long time to find
      the right path to curb the upward trend in these diseases. In this commentary,
      the authors review the evolution of strategies and the healthcare service system,
      examine advances and challenges, and summarize experience and lessons in NCD
      control in China. In view of development, China's experience may have valuable
      implications for other low- and middle-income countries.

PMID- 29226759
TI  - Evaluation and interpretation of the bucket test in healthy individuals.
AB  - OBJECTIVE: To determine and interpret the range of normal deviation of the bucket
      test in healthy subjects Subjects and methods: Study design: Cross-sectional
      study in a secondary care center. INCLUSION CRITERIA: subjects >=18 years old
      with no otologic or neurologic symptoms and normal complete neuro-otological
      examination. The subjective visual vertical was evaluated binocularly using the
      bucket test. Five measurements were made on the clockwise direction and five on
      the counterclockwise direction. The examiner selected the starting point, the
      patient then manipulated the bucket and it stopped when the volunteer considered
      the line reached the vertical position. RESULTS: Fifty healthy volunteers were
      included, 16 (32%) were men, and 34 (68%) women with a mean age of 34 years. The
      mean value found clockwise was 1.93 degrees  +/- 2.26 degrees  and
      counterclockwise sense was of 0.86 degrees  +/- 2.44 degrees . Mean normal values
      ranged from 1.4 degrees  +/- 1.9 degrees . CONCLUSIONS: The bucket test is easy
      and quick to perform; we recommend to use a range of -1.0 degrees  to +3.0
      degrees  as normal values in the healthy population.

PMID- 29226761
TI  - Neonatal cerebral lesions predict 2-year neurodevelopmental impairment in
      children treated with laser surgery for twin-twin transfusion syndrome:
      methodological issues.

PMID- 29226762
TI  - Assessing cognitive functioning in individuals with cocaine use disorder.
AB  - INTRODUCTION: There have been mixed findings assessing the impact of regular
      cocaine use on cognitive functioning. This study employed a comprehensive
      cognitive battery to compare the performance of individuals diagnosed with a
      cocaine use disorder (N = 3 abusers, N = 17 dependent) against the performance of
      two control groups: (a) non-drug-users, and (b) marijuana users who report no
      cocaine use (N = 7 marijuana abusers, N = 0 dependent, N = 13 marijuana users
      with no Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, DSM
      IV, diagnosis). METHOD: This one-session, between-participants, outpatient study
      was conducted at the New York State Psychiatric Institute. Sixty research
      volunteers completed the study. Drug users in both groups had no signs of current
      intoxication, but had a positive urine toxicology-which indicated use within 72
      hours in the cocaine use disorder group and within the past 30 days (depending on
      frequency of use) for the marijuana-using control group. The National Institutes
      of Health (NIH) Toolbox Cognition Battery was used to assess cognitive
      functioning across six domains: executive function, attention, episodic memory,
      working memory, processing speed, and language. Each participant's score was also
      compared against a normative database adjusted for age. RESULTS: Although the
      mean cognitive scores for all groups fell within the normal range for all tests,
      marijuana-using control participants outperformed those with a cocaine use
      disorder on a cognitive flexibility and language measure. CONCLUSIONS: Cognitive
      functioning of individuals diagnosed with cocaine use disorder was observed to be
      similar to that of control group participants on the majority of tasks and fell
      within the normal range when compared against normative data.

PMID- 29226763
TI  - MIPSS70: Mutation-Enhanced International Prognostic Score System for
      Transplantation-Age Patients With Primary Myelofibrosis.
AB  - Purpose To develop a prognostic system for transplantation-age patients with
      primary myelofibrosis (PMF) that integrates clinical, cytogenetic, and mutation
      data. Patients and Methods The study included 805 patients with PMF age <= 70
      years recruited from multiple Italian centers and the Mayo Clinic (Rochester,
      MN), forming two independent learning and validation cohorts. A Cox multivariable
      model was used to select from among a list of 22 variables those that were
      predictive of overall survival (OS). Integrated clinical and genetic prognostic
      models with (MIPSS70-plus) or without (MIPSS70) cytogenetic information were
      developed. Results Multivariable analysis identified the following as significant
      risk factors for OS: hemoglobin < 100 g/L, leukocytes > 25 * 109/L, platelets <
      100 * 109/L, circulating blasts >= 2%, bone marrow fibrosis grade >= 2,
      constitutional symptoms, absence of CALR type-1 mutation, presence of high
      molecular risk mutation (ie, ASXL1, EZH2, SRSF2, IDH1/ 2), and presence of two or
      more high-molecular risk mutations. By assigning hazard ratio (HR)-weighted
      points to these variables, three risk categories were delineated for the MIPSS70
      model; 5-year OS was 95% in low-risk, 70% in intermediate-risk, and 29% in high
      risk categories, corresponding to median OS of 27.7 years (95% CI, 22 to 34
      years), 7.1 years (95% CI, 6.2 to 8.1 years), and 2.3 years (95% CI, 1.9 to 2.7
      years), respectively. In the MIPSS70-plus model, which included cytogenetic
      information, four risk categories were delineated, with 5-year OS of 91% in low
      risk, 66% in intermediate-risk (HR, 3.2; 95% CI, 1.9 to 5.2), 42% in high-risk
      (HR, 6.4; 95% CI, 4.1 to 10.0), and 7% very high-risk categories (HR, 17.0; 95%
      CI, 9.8 to 29.2). Both models remained effective after inclusion of older
      patients in the analysis. Conclusion MIPSS70 and MIPSS70-plus provide
      complementary systems of risk stratification for transplantation-age patients
      with PMF and integrate prognostically relevant clinical, cytogenetic, and
      mutation data.

PMID- 29226760
TI  - The diagnostic performance of the beta-glucan assay in the detection of intra
      amniotic infection with Candida species.
AB  - INTRODUCTION: A bioassay based on the detection of beta-glucan, a constituent of
      the cell wall of fungi, has been successfully used to diagnose fungal infections
      in a variety of biological fluids but not yet in the amniotic fluid. OBJECTIVE:
      To determine the diagnostic performance of a beta-glucan bioassay in the
      detection of Candida species in the amniotic fluid of women who either did or did
      not have an intrauterine contraceptive device (IUD) in place during an episode of
      spontaneous preterm parturition. METHODS: The study population comprised women
      who had a singleton pregnancy without congenital or chromosomal abnormalities,
      who experienced preterm labor or preterm prelabor rupture of the fetal membranes,
      and who underwent a transabdominal amniocentesis for clinical indications.
      Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria,
      genital mycoplasmas, and Candida species, and assayed for beta-glucan, using the
      (1->3)-beta-d-glucan-specific Limulus amebocyte lysate test (beta-glucan assay)
      in all cases. Amniotic fluid interleukin (IL)-6 assay results were also available
      for all cases. The beta-glucan assay takes about 1 hour to run: a concentration
      >80 pg/mL was considered positive for fungi. Sterile intra-amniotic inflammation
      of the amniotic cavity was defined by the presence of an amniotic fluid IL-6
      concentration >=2.6 ng/mL and a negative amniotic fluid culture. RESULTS: (1) One
      hundred ninety-seven (197) women met the study criteria, of whom 58 (29.4%) had
      an IUD in place; (2) 20 (10.2%) women had a culture of proven intra-amniotic
      Candida species-related infection, 19 of whom had a positive beta-glucan assay
      [sensitivity, 95% (19/20; 95% confidence interval (CI): 75.1-99.9%)]; and (3) the
      specificity of the beta-glucan assay was 75.1% [133/177; 95% CI: 68.1-99.9%]. It
      was affected by the presence of nonfungal intra-amniotic infections and an IUD,
      but not by the presence of sterile intra-amniotic inflammation, and there was a
      significant interaction between the presence of an IUD and nonfungal intra
      amniotic infections (estimated for the interaction effect = 2.1923, p value
      =.026). The assay's specificity was reduced when nonfungal intra-amniotic
      infections were diagnosed but only in women who did not have an IUD. Among women
      without an IUD, the assay's specificity was 91.4% (117/128); it was 93% (106/114)
      for those without intra-amniotic infection, and 78.6% (11/14) for those with a
      nonfungal intra-amniotic infection; the difference was not significant (p = .09).
      Among women with an IUD, the assay's specificity was 32.7% (16/49); 42.9% (9/21)
      for those with a nonfungal intra-amniotic infection; and 25% (7/28) for those
      without intra-amniotic infection; and the difference was significant (p = .03).
      CONCLUSIONS: The beta-glucan assay is a sensitive, rapid, point-of-care test used
      to diagnose intra-amniotic Candida species-related infection, and it has a high
      specificity in pregnant women who did not have an IUD in place.

PMID- 29226765
TI  - Never Declared Brain Dead Potential Organ Donors-An Additional Source of Donor
      Organs?
AB  - CONTEXT: Patients never declared brain dead may represent an additional source of
      donor organs. OBJECTIVE: To determine the number of likely brain dead potential
      donors who are never declared brain dead and to compare them with brain dead and
      donation after cardiac death potential organ donors. DESIGN, SETTING, AND
      PARTICIPANTS: This study was a retrospective chart review of all catastrophically
      brain-injured patients referred to a single-organ procurement organization (OPO)
      over a 4-year period. This study identified 159 likely brain dead potential organ
      donors, 902 brain dead potential organ donors, and 357 potential donation after
      circulatory death donors over a 4-year period. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: This study did not predetermine outcome measures before data collection
      because the study group, likely brain dead potential organ donors, had not
      previously been described. RESULTS: Likely brain dead potential donors were
      significantly older than brain dead potential donors ( P < .0001) but were
      otherwise not different demographically. They were more likely to be a late
      referral to the OPO ( P < .0001) and less likely to be in the donor registry ( P
      < .0001). The most commonly identified factors associated with a failure to
      declare brain death were an unwillingness to continue supportive care by the
      family, premention of donation, a nontimely imminent death referral, known prior
      objection to donation, terminal instability, and a lack of cooperation with the
      OPO.

PMID- 29226766
TI  - A Case Report of Living Donor Liver Transplantation for Fulminant Hepatitis
      Related to Hepatitis E Virus Infection.
AB  - Hepatitis E virus (HEV) infection which may become fulminant, especially in
      elderly people is more common than previously recognized in develop countries.
      Here we report successful living-donor liver transplantation (LDLT) in a case of
      acute liver failure due to HEV. A 63-year-old Japanese man with no previous
      history of liver disease was admitted for severe acute hepatitis. Detection of
      anti-HEV immunoglobulin A established a diagnosis of this virus-related liver
      failure. The patient suffered from hepatic encephalopathy 10 days after symptom
      onset and underwent LDLT. The patient had an uneventful course. The HEV RNA
      showed spontaneous negative conversion 10 weeks after LDLT. LDLT led to a
      successful outcome in a patient with acute liver failure due to HEV infection and
      regular testing for HEV RNA should be performed until HEV RNA is undetectable.

PMID- 29226764
TI  - Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas.
AB  - BACKGROUND: Patients with diffuse large B-cell lymphoma or follicular lymphoma
      that is refractory to or that relapses after immunochemotherapy and
      transplantation have a poor prognosis. High response rates have been reported
      with the use of T cells modified by chimeric antigen receptor (CAR) that target
      CD19 in B-cell cancers, although data regarding B-cell lymphomas are limited.
      METHODS: We used autologous T cells that express a CD19-directed CAR (CTL019) to
      treat patients with diffuse large B-cell lymphoma or follicular lymphoma that had
      relapsed or was refractory to previous treatments. Patients were monitored for
      response to treatment, toxic effects, the expansion and persistence of CTL019
      cells in vivo, and immune recovery. RESULTS: A total of 28 adult patients with
      lymphoma received CTL019 cells, and 18 of 28 had a response (64%; 95% confidence
      interval [CI], 44 to 81). Complete remission occurred in 6 of 14 patients with
      diffuse large B-cell lymphoma (43%; 95% CI, 18 to 71) and 10 of 14 patients with
      follicular lymphoma (71%; 95% CI, 42 to 92). CTL019 cells proliferated in vivo
      and were detectable in the blood and bone marrow of patients who had a response
      and patients who did not have a response. Sustained remissions were achieved, and
      at a median follow-up of 28.6 months, 86% of patients with diffuse large B-cell
      lymphoma who had a response (95% CI, 33 to 98) and 89% of patients with
      follicular lymphoma who had a response (95% CI, 43 to 98) had maintained the
      response. Severe cytokine-release syndrome occurred in 5 patients (18%). Serious
      encephalopathy occurred in 3 patients (11%); 2 cases were self-limiting and 1
      case was fatal. All patients in complete remission by 6 months remained in
      remission at 7.7 to 37.9 months (median, 29.3 months) after induction, with a
      sustained reappearance of B cells in 8 of 16 patients and with improvement in
      levels of IgG in 4 of 10 patients and of IgM in 6 of 10 patients at 6 months or
      later and in levels of IgA in 3 of 10 patients at 18 months or later.
      CONCLUSIONS: CTL019 cells can be effective in the treatment of relapsed or
      refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of
      durable remission were observed, with recovery of B cells and immunoglobulins in
      some patients. Transient encephalopathy developed in approximately one in three
      patients and severe cytokine-release syndrome developed in one in five patients.
      (Funded by Novartis and others; ClinicalTrials.gov number, NCT02030834 .).

PMID- 29226767
TI  - A systems approach to extraordinarily major coal mine accidents in China from
      1997 to 2011: an application of the HFACS approach.
AB  - This study aimed to provide a greater understanding of the systemic factors
      involved in coal mine accidents and to examine the relationships between the
      contributing factors across all levels of the system. Ninety-four extraordinarily
      major coal mine accidents that occurred in China from 1997 to 2011 were analyzed
      using the human factors analysis and classification system (HFACS). The empirical
      results showed that the frequencies of unsafe behaviors, inadequate regulation
      and failure to correct hidden dangers were the highest among five levels, 14
      categories and 48 indicators, respectively. The odds ratio technique was applied
      to quantitatively examine the relationships between contributing factors. Various
      statistically significant associations were discovered and should receive greater
      attention in future attempts to develop accident measures. In addition, several
      strategies concerning the main contributing factors and routes to failure are
      proposed to prevent accidents from reoccurring in an organization.

PMID- 29226768
TI  - Algal treatment of wastewater generated during oil and gas production using
      hydraulic fracturing technology.
AB  - Hydraulic fracturing technology is widely used for recovering natural gas and oil
      from tight oil and gas reserves. Large volumes of wastewater, flowback water, are
      produced during the fracturing process. This study examines algal treatment of
      flowback water. Thirteen microalgae strains consisting of cyanobacteria and green
      algae were examined. Wastewater quality before and after algae treatment, as well
      as volatile matter, fixed carbon and ash contents of the biomass grown in
      flowback water were examined. The experimental results demonstrated that
      microalgae can grow in flowback water. The chemical composition of the algal
      biomass produced in flowback water was strain specific. Over 65% total dissolved
      solids, 100% nitrate and over 95% boron reduction in flowback water could be
      achieved. Hence, algal treatment of flowback water can significantly reduce the
      adverse environmental impact of hydraulic fracturing technology and produce
      biomass that can be converted to bioproducts.

PMID- 29226769
TI  - Working memory capacity and the spacing effect in cued recall.
AB  - Spacing repetitions typically improves memory (the spacing effect). In three cued
      recall experiments, we explored the relationship between working memory capacity
      and the spacing effect. People with higher working memory capacity are more
      accurate on memory tasks that require retrieval relative to people with lower
      working memory capacity. The experiments used different retention intervals and
      lags between repetitions, but were otherwise similar. Working memory capacity and
      spacing of repetitions both improved memory in most of conditions, but they did
      not interact, suggesting additive effects. The results are consistent with the
      ACT-R model's predictions, and with a study-phase recognition process
      underpinning the spacing effect in cued recall.

PMID- 29226770
TI  - An unexpected image on a chest radiograph.
AB  - Introduction Central venous catheterisation is an essential component of patient
      care in hospital. A forgotten complete guide-wire is a rare complication,
      although the reported incidence has increased rapidly over the last decade. Case
      report We report a 72-year-old man with a complete guide-wire inadvertently
      overlooked during catheter insertion. A central venous catheter had been inserted
      for total parental nutrition during treatment for pancreatitis. Five years later,
      the patient was readmitted with a painful lesion on his neck and the sensation of
      a sharp object under his skin. He was discharged without complication following
      removal of the free part of the guide-wire that had not become attached to the
      endothelial layer. Conclusion Inattention, inexperience and lack of supervision
      by a more experienced clinician are considered the most important contributing
      factors to this complication. Ultrasonography assistance during the procedure,
      senior supervision, a set count and a chest X-ray after the procedure are
      recommended in order to prevent forgotten guide-wires.

PMID- 29226771
TI  - Men's Mental Health Help-Seeking Behaviors: An Intersectional Analysis.
AB  - Men seek mental health treatment less often than women. The present study sought
      to elucidate identities and individual difference characteristics that are
      associated with enhanced or decreased mental health help-seeking in a large
      national sample of U.S. men. Using data from 4,825 U.S. men aged 20 to 59 years,
      main effects of race/ethnicity, sexual orientation, age, income-poverty ratio,
      relationship status, depression symptoms, and body mass index were explored
      within the sample of men as well as intersections of these predictors with
      racial/ethnic group identity. While the results of main effects testing generally
      supported prior research (i.e., greater mental health care help-seeking among
      White men, nonheterosexual men, men not in relationships, older men, and more
      depressed men), when examined associations across racial/ethnic groups, the
      direction and strength of these associations showed notable variation-variation
      unaccounted for in prior research. These findings highlight the need for future
      theory building and research that accounts for this variation at the intersection
      of race/ethnicity and these specific predictors of help-seeking behavior among
      men.

PMID- 29226773
TI  - Exercise Effects for Children With Autism Spectrum Disorder: Metabolic Health,
      Autistic Traits, and Quality of Life.
AB  - This study examined the effects of a 48-week exercise-based intervention on the
      metabolic profile, autism traits, and perceived quality of life in children with
      autism spectrum disorder (ASD). We randomly allocated 64 children with ASD (aged
      6-12 years) to experimental ( n = 46) and control groups ( n = 18) and used
      multilevel regression modeling to examine responses to receiving or not receiving
      the intervention. The experimental group showed beneficial effects on metabolic
      indicators (high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and total cholesterol), autism traits, and parent-perceived quality
      of life. Our results provide support for exercise and physical activity,
      including basic coordination and strength exercises, as important therapeutic
      interventions for children with ASD.

PMID- 29226774
TI  - Introduction to the Special Issue on Rare and Unusual Syndromes.

PMID- 29226775
TI  - Corrigendum: The Wisdom in Virtue: Pursuit of Virtue Predicts Wise Reasoning
      About Personal Conflicts.
AB  - Original Article: Huynh, A. C., Oakes, H., Shay, G. R., & McGregor, I. (2017).
      The wisdom in virtue: Pursuit of virtue predicts wise reasoning about personal
      conflicts. Psychological Science, 28, 1848-1856. doi:10.1177/0956797617722621 In
      this article, results for the Pursuit of Virtue * Conflict Type interaction in
      Study 2 were incorrectly reported. The final paragraph on page 1854 stated, "As
      in Study 1, we found a significant Pursuit of Virtue * Conflict Type interaction,
      F(1, 353) = 4.61, p = .032, eta p2 = .01, 95% CI = [.0001, .05]." These results
      were taken from an analysis of standardized ( z-scored) dependent variables, but
      because Study 2 involved a repeated measures design, standardization did not
      allow the model to account for overall changes in reasoning between the two
      measures. Because our reported procedure did not involve standardizing the
      measures, this sentence is now being corrected to read as follows: The pattern of
      means was similar to that obtained in Study 1, although in this study, the
      Pursuit of Virtue * Conflict Type interaction was not statistically significant,
      F(1, 353) = 3.37, p = .067, eta p2 = .01, 95% CI = [.00, .04]. Because this
      interaction is relevant to the primary findings, the authors acknowledge that
      Study 2 provides converging, but not statistically significant, support for the
      findings in Study 1. As a result of the same error, the reported p value for the
      moderation test of Hedonic motivation in the following paragraph (p. 1855) was
      also incorrect. The sentence reporting these results is being corrected to read:
      "Hedonic motivation did not moderate the effect of conflict type, F(1, 353) < 1,
      p = .323 (see the Supplemental Material for additional details)." The error in
      the presentation of these results did not affect the subsequent reported results
      for the simple effects in Study 2 or the analysis of the subcomponents of wise
      reasoning. The reported results for Study 1 were not affected by this error.

PMID- 29226776
TI  - A Journal-Level Analysis of Progress in Transplantation.
AB  - CONTEXT: Citations to articles published in academic journals represent a proxy
      for influence in bibliometrics. OBJECTIVE: To measure the journal impact factor
      for Progress in Transplantation over time and to also identify related journals
      indexed in transplantation and surgery. DESIGN: Data from Journal Citation
      Reports (ISI web of science) were used to rank Progress in Transplantation
      compared to peer journals using journal impact and journal relatedness measures.
      Social network analysis was used to measure relationships between pairs of
      journals in Progress in Transplantation's relatedness network. MAIN OUTCOME
      MEASURES: Journal impact factor and journal relatedness. RESULTS: Data from 2010
      through 2015 indicate the average journal article in PIT was cited 0.87 times
      (standard deviation [SD] = 0.12) and this estimate was stable over time. Progress
      in Transplantation most often cited American Journal of Transplantation,
      Transplantation, American Journal of Kidney Diseases, and Liver Transplantation.
      In terms of cited data, the journal was most often referenced by Clinical
      Transplantation, Transplant International, and Current Opinion in Organ
      Transplantation. CONCLUSION: The journal is listed both in surgery and
      transplantation categories of Journal Citation Reports and its impact factors
      over time fare better with surgery journals than with transplant journals.
      Network data using betweenness centrality indicate Progress in Transplantation
      links transplantation-focused journals and journals indexed in health sciences
      categories.

PMID- 29226777
TI  - Collaborative-controlled LASSO for constructing propensity score-based estimators
      in high-dimensional data.
AB  - Propensity score-based estimators are increasingly used for causal inference in
      observational studies. However, model selection for propensity score estimation
      in high-dimensional data has received little attention. In these settings,
      propensity score models have traditionally been selected based on the goodness-of
      fit for the treatment mechanism itself, without consideration of the causal
      parameter of interest. Collaborative minimum loss-based estimation is a novel
      methodology for causal inference that takes into account information on the
      causal parameter of interest when selecting a propensity score model. This
      "collaborative learning" considers variable associations with both treatment and
      outcome when selecting a propensity score model in order to minimize a bias
      variance tradeoff in the estimated treatment effect. In this study, we introduce
      a novel approach for collaborative model selection when using the LASSO estimator
      for propensity score estimation in high-dimensional covariate settings. To
      demonstrate the importance of selecting the propensity score model
      collaboratively, we designed quasi-experiments based on a real electronic
      healthcare database, where only the potential outcomes were manually generated,
      and the treatment and baseline covariates remained unchanged. Results showed that
      the collaborative minimum loss-based estimation algorithm outperformed other
      competing estimators for both point estimation and confidence interval coverage.
      In addition, the propensity score model selected by collaborative minimum loss
      based estimation could be applied to other propensity score-based estimators,
      which also resulted in substantive improvement for both point estimation and
      confidence interval coverage. We illustrate the discussed concepts through an
      empirical example comparing the effects of non-selective nonsteroidal anti
      inflammatory drugs with selective COX-2 inhibitors on gastrointestinal
      complications in a population of Medicare beneficiaries.

PMID- 29226778
TI  - A multicenter randomized controlled trial of two group education programs for
      fatigue in multiple sclerosis: Short- and medium-term benefits.
AB  - Background Fatigue occurs in 75%-95% of people with multiple sclerosis (MS) and
      is frequently reported as the most disabling symptom. A multicomponent group
      program of six weekly 2-hour sessions, Fatigue: Take Control (FTC), was developed
      from an international MS fatigue management guideline. Objective To determine
      whether FTC is associated with greater improvements in fatigue than MS: Take
      Control (MSTC), a similarly structured general MS education program. Methods This
      four-site, parallel, single-blind, randomized controlled trial compared FTC and
      MSTC in 204 ambulatory participants with MS. The primary outcome, the Modified
      Fatigue Impact Scale (MFIS), and secondary outcomes of self-efficacy, physical
      activity, sleep, and medications were assessed at baseline, program completion,
      and 3 and 6 months later. Results Mean MFIS scores improved in both groups
      between baseline and program completion (FTC -4.4, p < 0.001; MSTC -3.8, p <
      0.001), between baseline and 3 months after program completion (FTC -3.2, p =
      0.01; MSTC -3.3, p = 0.01), and between baseline and 6 months after program
      completion (FTC -5.2, p < 0.001; MSTC -4.8, p < 0.001). These improvements were
      not statistically different between groups ( p = 0.64, 0.92, and 0.82,
      respectively). Conclusion Participation in FTC modestly improved self-reported
      fatigue for up to 6 months. This improvement did not differ significantly from
      that occurring with the control program.

PMID- 29226779
TI  - Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast
      cortical atrophy and longitudinal functional deterioration in relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Currently, no unequivocal predictors of disease evolution exist in
      patients with multiple sclerosis (MS). Cortical atrophy measurements are,
      however, closely associated with cumulative disability. OBJECTIVE: Here, we aim
      to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy
      and clinical disability from cerebrospinal fluid (CSF) markers. METHODS: We
      analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their
      CSF to serum quotients. RESULTS: Widespread atrophy was highly associated with
      increased baseline CSF concentrations and quotients of albumin and IgA. Patients
      with increased CSFIgA and CSFIgM showed higher functional disability at follow
      up. CONCLUSION: CSF markers of blood-brain barrier integrity and specific immune
      response forecast emerging gray matter pathology and disease progression in MS.

PMID- 29226780
TI  - Individuals' perception about upper limb influence on participation after stroke:
      an observational study.
AB  - Background Stroke can compromise upper limb performance and influence the
      individual's participation in real life situations. Objective To investigate how
      components of body function and activity affect the individuals' self-perception
      of their participation after stroke. Methods In this observational study, the
      International Classification of Functioning, Disability and Health was used as
      model. Body function was assessed by palmar grip and pinch strength; Ashworth
      modified scale; Fugl-Meyer scale; and Motor-Free Visual Perception Test. The
      Purdue Pegboard Test and the aiming movement performance measured the activity.
      Upper limb participation was analyzed by the Hand Function domain of the Stroke
      Impact Scale (SIS). Thirty-four individuals after chronic stroke were divided
      into two groups, according to their Hand function SIS scores (severe and non
      severe). Differences between groups were analyzed. Relationships between
      individual variables and the SIS score were verified. A regression model was
      proposed. Results Strength and the Fugl-Meyer scale score were greater for the
      non-severe group. Muscle tone was greater for the severe group only in the wrist
      flexors. None of the activity variables differed between groups. The upper limb
      Fugl-Meyer score was able to predict 79% of the individuals in SIS Hand Function
      groups. Conclusion Sensory-motor impairment, as measured by the upper limb Fugl
      Meyer scale, can explain the influence of the upper limbs on participation in the
      individuals' perception.

PMID- 29226781
TI  - A Milestone for CAR T Cells.

PMID- 29226782
TI  - Patterns of source monitoring bias in incarcerated youths with and without
      conduct problems.
AB  - INTRODUCTION: Antisocial individuals present behaviours that violate the social
      norms and the rights of others. In the present study, we examine whether biases
      in monitoring the self-generated cognitive material might be linked to antisocial
      manifestations during adolescence. We further examine the association with
      psychopathic traits and conduct problems (CPs). METHODS: Sixty-five incarcerated
      adolescents (IAs; M age = 15.85, SD = 1.30) and 88 community adolescents (CAs; M
      age = 15.78, SD = 1.60) participated in our study. In the IA group, 28
      adolescents presented CPs (M age = 16.06, SD = 1.41) and 19 did not meet the
      diagnostic criteria for CPs (M age = 15.97, SD = 1.20). Source monitoring was
      assessed through a speech-monitoring task, using items requiring different levels
      of cognitive effort; recognition and source-monitoring bias scores (internalising
      and externalising biases) were calculated. RESULTS: Between-group comparisons
      indicate greater overall biases and different patterns of biases in the source
      monitoring. IA participants manifest a greater externalising bias, whereas CA
      participants present a greater internalising bias. In addition, IA with CPs
      present different patterns of item recognition. CONCLUSIONS: These results
      indicate that the two groups of adolescents present different types of source
      monitoring bias for self-generated speech. In addition, the IAs with CPs present
      impairments in item recognition. Future studies may examine the developmental
      implications of self-monitoring biases in the perseverance of antisocial
      behaviours from adolescence to adulthood.

PMID- 29226783
TI  - Evaluation of the water disinfection by-product dichloroacetonitrile-induced
      biochemical, oxidative, histopathological, and mitochondrial functional
      alterations: Subacute oral toxicity in rats.
AB  - Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is
      more genotoxic and cytotoxic than the currently regulated carbonaceous
      disinfection by-products such as haloacetic acids. Few mechanistic studies have
      been conducted on the hepatic and renal toxicities of DCAN. This study examined
      the clinical biochemical, hematological, histopathological, oxidative, and
      mitochondrial functional alterations to evaluate the systematic toxicity after
      subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen
      weights were lower, and organ-to-body weight ratios of the liver and kidney were
      higher in rats administered 44-mg/kg DCAN than in controls. The activities of
      serum alanine aminotransferase and alkaline phosphatase, and concentrations of
      blood serum urea nitrogen and retinol-binding protein were increased in rats
      administered 44-mg/kg DCAN compared with those of controls, thereby indicating
      hepatic and renal damage in this group. This was confirmed by histopathological
      alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar
      degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling,
      in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage
      shown by the significant increase in malonaldehyde levels, a poisonous product of
      lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic
      glutathione content and mitochondrial bioenergy as noted by the elevation of
      mitochondrial membrane potential and cytochrome c oxidase activity, which might
      be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic
      mitochondrial damage.

PMID- 29226784
TI  - The reproductive and developmental toxicity of nanoparticles: A bibliometric
      analysis.
AB  - Because of the advantages of nanoparticles (NPs) in a variety of industrial,
      biomedical, and consumer applications, they are intentionally (such as in
      medicine) or unintentionally (environment exposure) introduced into the human
      body. However, to date, the detrimental effects of NPs are still unclear,
      especially in reproductive and developmental toxicity. In this study, we
      researched 266 articles related to the reproductive and developmental toxicity of
      NPs from 2006 to December 2016 based on the database of the Web of Science.
      According to the bibliometric analysis, we found that China and the United States
      were the leading countries in this field and the major research trends might
      focus on the pathogenesis of NPs, such as oxidative stress, inflammation, and DNA
      damage. By this analysis, we provide new insights into the research trends and
      characteristics of the field.

PMID- 29226785
TI  - Facial First Impressions Across Culture: Data-Driven Modeling of Chinese and
      British Perceivers' Unconstrained Facial Impressions.
AB  - People form first impressions from facial appearance rapidly, and these
      impressions can have considerable social and economic consequences. Three
      dimensions can explain Western perceivers' impressions of Caucasian faces:
      approachability, youthful-attractiveness, and dominance. Impressions along these
      dimensions are theorized to be based on adaptive cues to threat detection or
      sexual selection, making it likely that they are universal. We tested whether the
      same dimensions of facial impressions emerge across culture by building data
      driven models of first impressions of Asian and Caucasian faces derived from
      Chinese and British perceivers' unconstrained judgments. We then cross-validated
      the dimensions with computer-generated average images. We found strong evidence
      for common approachability and youthful-attractiveness dimensions across
      perceiver and face race, with some evidence of a third dimension akin to
      capability. The models explained ~75% of the variance in facial impressions. In
      general, the findings demonstrate substantial cross-cultural agreement in facial
      impressions, especially on the most salient dimensions.

PMID- 29226786
TI  - Temporal grouping effects in musical short-term memory.
AB  - Recent theoretical accounts of verbal and visuo-spatial short-term memory (STM)
      have proposed the existence of domain-general mechanisms for the maintenance of
      serial order information. These accounts are based on the observation of similar
      behavioural effects across several modalities, such as temporal grouping effects.
      Across two experiments, the present study aimed at extending these findings, by
      exploring a STM modality that has received little interest so far, STM for
      musical information. Given its inherent rhythmic, temporal and serial
      organisation, the musical domain is of interest for investigating serial order
      STM processes such as temporal grouping. In Experiment 1, the data did not allow
      to determine the presence or the absence of temporal grouping effects. In
      Experiment 2, we observed that temporal grouping of tone sequences during
      encoding improves short-term recognition for serially presented probe tones.
      Furthermore, the serial position curves included micro-primacy and micro-recency
      effects, which are the hallmark characteristic of temporal grouping. Our results
      suggest that the encoding of serial order information in musical STM may be
      supported by temporal positional coding mechanisms similar to those reported in
      the verbal domain.

PMID- 29226787
TI  - Bayesian proportional hazards model with latent variables.
AB  - We consider a joint modeling approach that incorporates latent variables into a
      proportional hazards model to examine the observed and latent risk factors of the
      failure time of interest. An exploratory factor analysis model is used to
      characterize the latent risk factors through multiple observed variables. In
      commonly used confirmatory factor analysis, the number of latent variables and
      their observed indicators are specified prior to analysis. By contrast, the
      exploratory factor analysis model allows such information to be fully determined
      by the data. A Bayesian approach coupled with efficient sampling methods is
      developed to conduct statistical inference, and the performance of the proposed
      methodology is confirmed through simulations. The model is applied to a study on
      the risk factors of chronic kidney disease for patients with type 2 diabetes.

PMID- 29226788
TI  - Mental health for refugees, asylum seekers and displaced persons: A call for a
      humanitarian agenda.

PMID- 29226789
TI  - The emotional distress of asylum seekers in Israel and the characteristics of
      those seeking psychiatric versus medical help.
AB  - Israel has become a destination for asylum seekers. Asylum seekers often
      experience emotional distress, but have limited access to health services and
      rarely use psychiatric services. This study sought to understand and characterize
      the use of psychiatric versus medical services by asylum seekers in Israel. We
      compared the emotional distress, stressful life events and previous treatment
      consultations of 21 psychiatric service users (PSU) and 55 medical service users
      (MSU) at the Open Clinic of Physicians for Human Rights in Tel-Aviv. Participants
      completed a socio-demographic questionnaire, the General Health Questionnaire
      (GHQ-12), the Stressful Life Events Scale and the Health Care Utilization
      Questionnaire. PSU and MSU did not have significantly different levels of
      emotional distress. PSU reported significantly more stressful life events during
      the past year than MSU ( M = 5.81, SD 3.47 vs. M = 3.8, SD 2.35, p < 0.01). In
      comparison to MSU, PSU utilized more medical ( M = 4.33, SD 2.28) and non-medical
      ( M = 2.38, SD 1.92) services ( p < 0.001) than MSU. Asylum seekers who consulted
      multiple treatment agencies in the last year were 1.55 times more likely to seek
      psychiatric treatment than those who had consulted only a few treatment agencies.
      Emotional distress in asylum seekers appears to be under-diagnosed in the Open
      Clinic and under-treated by mental health professionals. To better detect this
      distress, a thorough screening is recommended at assessment. Collaboration with
      mental health professionals and community and religious leaders consulted in the
      past is important and can contribute to good health care outcomes in this
      population.

PMID- 29226790
TI  - Posttraumatic stress disorder and comorbid depression among refugees: Assessment
      of a sample from a German refugee reception center.
AB  - In 2015, a large number of refugees arrived in Germany, mostly driven to emigrate
      by devastating circumstances in their countries of origin. Arriving refugees are
      distributed to reception centers within the German federal states, frequently
      facing marginal conditions in terms of overcrowding or waiting time of several
      months until their application for asylum is processed. Most of these refugees
      underwent numerous traumatizing experiences-both in their country of origin and
      while fleeing from their country of origin. Furthermore, they faced and will
      likely continue to face various access barriers to mental health care. In this
      study, we assessed a sample of 85 refugees from a reception center in Germany
      selected due to their observed psychological strain. Results showed that the
      majority suffered from posttraumatic stress disorder, mostly with symptoms of
      intrusion, hyperarousal, avoidance, and dissociation. Most refugees also suffered
      from comorbid depression. We discuss implications of these findings for reception
      services and the need for more preventive psychiatric care.

PMID- 29226791
TI  - Counting the cost of Afrophobia: Post-migration adaptation and mental health
      challenges of African refugees in South Africa.
AB  - There are few studies on the role of migration within sub-Saharan Africa and its
      relation to the development of mental illness. We investigated post-resettlement
      adaptation and mental health challenges of African refugees/migrants in Durban,
      South Africa. We interviewed 335 African help-seeking refugees/migrants for
      anxiety, depression (25-item Hopkins Symptom Checklist) and post-traumatic stress
      symptoms (30-item Harvard Trauma Questionnaire). Socio-demographic and migration
      history, focusing on post-migration circumstances and experiences of
      discrimination in the host country, were obtained. Association between migration
      and post-settlement factors and mental health outcomes were assessed using
      adjusted logistic regression models. Prevalence of mental distress was high:
      49.4% anxiety, 54.6% depression and 24.9% post-traumatic stress symptoms. After
      adjustment for family separation since migration, recent arrival in South Africa
      was associated with increased risk for depression (aOR = 4.0, 95% CI:1.3-11.8)
      and post-traumatic stress (aOR = 5.2, 95% CI:1.7-15.9), while in unadjusted
      models, older age on arrival was associated with anxiety (aOR = 5.3, 95% CI:1.4
      19.8) and depression (aOR = 6.2, 95% CI:1.6-24.3). History of family separation
      since migration was independently associated with depression and post-traumatic
      stress in all models. Discriminatory experiences since migration was also an
      independent risk factor for all three mental health outcomes. Finally, being
      divorced/widowed was associated with an increased risk for post-traumatic stress,
      while higher income earners were protected against post-traumatic symptoms, even
      after adjustment. Refugees/migrants in South Africa show a significant burden of
      mental distress that is linked to challenges of adjustment in an often hostile
      context. Services addressing these and other health-related, social-economic
      needs should be developed as a priority.

PMID- 29226792
TI  - Posttraumatic world assumptions among treatment-seeking refugees.
AB  - The clinical relevance of negative changes in cognitions about oneself, others,
      and the world is reflected in the diagnostic criteria for posttraumatic stress
      disorder (PTSD) in the DSM-5 and complex posttraumatic stress disorder in the ICD
      11. Although such changes in cognition have been posited to be especially
      relevant for traumatised refugees, few studies have examined this in refugee
      populations. The present study used a cross-sectional design to compare negative
      cognitions among 213 adult treatment-seeking refugees with those in previously
      published samples from the general population, veterans with combat-related PTSD,
      and whiplash victims. Measures included the World Assumptions Scale (WAS) and the
      Events and DSM-IV PTSD subscales of the Harvard Trauma Questionnaire (HTQ). Path
      models examined the relation of the WAS subscales to five demographic and trauma
      related variables. Results showed that world assumptions were especially negative
      with regard to Benevolence of World, Benevolence of People, and Luck subscales,
      on which refugees scored lower than all reference samples. Differences between
      the refugee sample and the reference samples were smallest with regard to self
      worth and self-controllability. World assumptions were associated with gender and
      PTSD symptom severity but not with age, length of residence in the Netherlands,
      and number of traumatic event types. The DSM-5 criterion of negative changes in
      belief about oneself, others, and the world appears more applicable to refugees
      than the more narrowly formulated ICD-11 criterion of diminished and defeated
      sense of self. Prevention and treatment efforts with refugees may need to be
      especially aimed at preventing a further decline of trust as well as restoration
      of trust in others and the world.

PMID- 29226793
TI  - Cultural translation of refugee trauma: Cultural idioms of distress among Somali
      refugees in displacement.
AB  - Westernized approaches to mental health care often place limited emphasis on
      refugees' own experiences and cultural explanations of symptoms and distress. In
      order to effectively assess community mental health needs and develop
      interventions grounded in local needs, mental health programs need to be informed
      by an understanding of cultural features of mental health, including cultural
      idioms of distress (CIDs). The current study aims to explore CIDs among Somali
      refugees displaced in Kenya to understand mental health needs in cultural context
      and serve the community in a culturally responsive and sensitive manner. This
      research was conducted as a two-phase qualitative study. First, key informant
      interviews with Somali mental health stakeholders generated a list of 7 common
      Somali CIDs: buufis, buqsanaan, welwel, murug, qaracan, jinn, and waali.
      Typologies of each CID were further explored through four focus group interviews
      with Somali community members. The findings from a template analysis revealed
      Somali lay beliefs on how trauma and daily stressors are experienced and
      discussed in the form of CIDs and how each term is utilized and understood in
      attributing symptoms to associated causes. This study highlights the need to
      incorporate colloquial terms in mental health assessment and to adopt a
      culturally relevant framework to encourage wider utilization of services and
      religious/spiritual support systems.

PMID- 29226794
TI  - Mental health of immigrants and refugees seeking legal services on the US-Mexico
      border.
AB  - The debates on the mental health benefits associated with immigration are mixed.
      On the one hand, immigrants are provided with more opportunities not available in
      their home countries. On the other hand, they are far away from home and may have
      been exposed to traumatic experiences on their journeys to the receiving country.
      Even after settling down in the receiving country, most continue to face legal
      battles associated with their immigration status, as shown in this study. This
      study examined the risk and protective factors associated with the mental health
      conditions in a sample of 39 immigrants and refugees seeking legal services on
      the US-Mexico border. Participants were recruited from a southwestern community
      agency serving the region's immigrant population over the past three decades.
      Negative mental health states including stress, sadness, and anxiety were
      frequently reported by the participants. Six themes were identified as
      significantly related to the participants' adjustment in the US: (1) political
      turmoil and safety issues; (2) economic hardship and extreme poverty; (3) trauma
      before and after resettlement; (4) immigration status; (5) family relational
      strain; and (6) identity struggle and acculturation. Overall, results demonstrate
      the complexity of issues pertaining to cross-country migration, cultural
      sensitivities, and mental health.

PMID- 29226795
TI  - Treatment of sleep disturbances in refugees suffering from post-traumatic stress
      disorder.
AB  - Sleep disturbances are often referred to as the hallmark of Post-Traumatic Stress
      Disorder (PTSD). Although PTSD is prevalent in refugees, studies on sleep
      disturbances in trauma-affected refugees are scarce. This article presents the
      results of two studies: a systematic review of the literature on treatment of
      sleep disturbances in adult trauma-affected refugees and a study of the role of
      sleep disturbances in the PTSD symptom structure. Study 1, the literature review,
      identified five studies on treatment of sleep disturbances: four studies were on
      pharmacological treatment and one study on music therapy. The identified studies
      had small sample sizes and few carried out statistical analysis. It was not
      possible from the available literature to recommend any specific treatment of
      sleep disturbances. In Study 2, a clinical sample of 752 refugees, fulfilling
      criteria for PTSD and enrolled in treatment at the Competence Centre for
      Transcultural Psychiatry, Denmark, completed the Harvard Trauma Questionnaire
      (HTQ) before and after treatment. To determine item discrimination, the data was
      tested with a Rasch model. 99.1% reported trouble sleeping and 98.7% reported
      recurrent nightmares. The Rasch analysis displayed fit residuals of 0.05 for
      trouble sleeping and -1.16 for nightmares, indicating sufficient discrimination.
      Trouble sleeping and nightmares proved important parts of the HTQ response
      structure. This study indicates that sleep disturbances are a prominent part of
      the PTSD symptom structure in refugees but that research on treatment of sleep
      disturbances is limited. Further research on sleep disturbances in trauma
      affected refugees is therefore needed.

PMID- 29226796
TI  - "If I speak English, what am I? I am full man, me": Emotional impact and barriers
      for refugees and asylum seekers learning English.
AB  - Lack of proficiency in the language of the host country predicts distress among
      refugees, but many refugees and asylum seekers in the United Kingdom have less
      than functional English. This study examined how learning English affected
      refugees' and asylum seekers' lives, particularly their emotional wellbeing, to
      explore what factors, particularly psychological ones, facilitated or impeded
      their learning English. We recruited 16 refugees and asylum seekers from an inner
      city National Health Service trauma service and from a charity providing one-to
      one English classes. All participants were interviewed in English. Interview data
      were analysed using thematic analysis from a critical realist perspective.
      Interviewees provided consistent accounts of their efforts to learn English,
      integrated into often unsettled and difficult lives. The analysis generated six
      themes in two domains. The impact of learning English was mainly positive,
      associated with autonomy, sense of achievement, and aspirations. Barriers to
      learning English consisted of other problems affecting refugees' capacity to
      learn, limited opportunities to speak English, and a sense of shame associated
      with perceived lack of English language competence. Findings highlight the need
      to provide adequate psychological support for refugees and asylum seekers
      learning English, recognising its importance in promoting both their integration
      in the UK and their individual psychological well-being.

PMID- 29226798
TI  - Long-term effects of a Swedish lifestyle intervention programme on lifestyle
      habits and quality of life in people with increased cardiovascular risk.
AB  - AIMS: The aim of this study was to evaluate the effects of a structured
      intervention programme on lifestyle habits and quality of life after six months
      and one year in participants with increased cardiovascular risk. METHODS:
      Participants aged >=18 years with increased cardiovascular risk were referred
      from primary health care and hospitals. The programme was launched at an
      outpatient clinic in a department of cardiology at a university hospital. It
      consisted of individual visits to a nurse for a health check-up and lifestyle
      counselling at baseline, after six months and at one year. In addition, five
      group sessions - focusing on nicotine, alcohol, physical activity, eating habits,
      stress, sleep and behavioural change - were offered to the participants and their
      relatives or friends. Lifestyle habits and quality of life were assessed with
      questionnaires at baseline, after six months and at one year. RESULTS: One
      hundred participants (64 women, 36 men, age 58+/-11 years) were included in the
      programme. Compared with the baseline, significant and favourable changes in
      reported lifestyle habits were noted. Exercise levels were higher after one year
      and sedentary time decreased from 7.4 to 6.3 h/day. Dietary habits improved and
      the number of participants with a high consumption of alcohol decreased. Quality
      of life improved after one year. CONCLUSIONS: Participating in a structured
      lifestyle programme resulted in improved lifestyle habits and quality of life
      over one year in people with increased cardiovascular risk. Components such as an
      inter-professional teamwork, a focus on lifestyle rather than the disease, and
      combining individual visits and group sessions, might be central to the positive
      outcome of the programme.

PMID- 29226799
TI  - Evaluation of a school-based cognitive-behavioral depression prevention program.
AB  - AIM: The aim of this study was to investigate the feasibility and cost-utility of
      a school-based cognitive-behavioral (CB) depression prevention program. METHODS:
      A quasi-experimental trial with an intervention group and a control group, with
      follow-up measurements obtained at three and 12 months after baseline, was
      conducted. The setting was six Swedish municipalities. The participants were
      students in grade 8 (median age: 14). A total of 462 students (79% girls) were
      allocated to the school-based CB prevention program, and 486 students (46% girls)
      were allocated to the control group. The school-based CB prevention program,
      Depression in Swedish Adolescents (DISA), was presented by school health service
      staff and teachers once per week for 10 weeks. RESULTS: The main outcome measures
      were self-reported depressive symptoms and self-rated health; the secondary
      outcome measures were adherence and cost-utility. The intervention group
      decreased their self-reported depressive symptoms (as measured by the Center for
      Epidemiological Studies Depression Scale) and improved their self-rated health
      (as measured by the visual analog scale) at the 12-month follow-up more than the
      control group ( p < .05). CONCLUSIONS: Given the challenges of conducting a study
      in a complex, everyday school setting with baseline differences between the
      intervention and control group, it is difficult to make accurate interpretations
      of the effectiveness of the intervention. However, with these limitations in
      mind, the results indicate that the DISA program is a feasible school-based
      prevention program.

PMID- 29226801
TI  - The Global Pandemic of Falsified Medicines: Laboratory and Field Innovations and
      Policy Implications.

PMID- 29226797
TI  - Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
AB  - BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous
      anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in
      patients with refractory large B-cell lymphoma after the failure of conventional
      therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients
      with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or
      transformed follicular lymphoma who had refractory disease despite undergoing
      recommended prior therapy. Patients received a target dose of 2*106 anti-CD19 CAR
      T cells per kilogram of body weight after receiving a conditioning regimen of low
      dose cyclophosphamide and fludarabine. The primary end point was the rate of
      objective response (calculated as the combined rates of complete response and
      partial response). Secondary end points included overall survival, safety, and
      biomarker assessments. RESULTS: Among the 111 patients who were enrolled, axi-cel
      was successfully manufactured for 110 (99%) and administered to 101 (91%). The
      objective response rate was 82%, and the complete response rate was 54%.With a
      median follow-up of 15.4 months, 42% of the patients continued to have a
      response, with 40% continuing to have a complete response. The overall rate of
      survival at 18 months was 52%. The most common adverse events of grade 3 or
      higher during treatment were neutropenia (in 78% of the patients), anemia (in
      43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome
      and neurologic events occurred in 13% and 28% of the patients, respectively.
      Three of the patients died during treatment. Higher CAR T-cell levels in blood
      were associated with response. CONCLUSIONS: In this multicenter study, patients
      with refractory large B-cell lymphoma who received CAR T-cell therapy with axi
      cel had high levels of durable response, with a safety profile that included
      myelosuppression, the cytokine release syndrome, and neurologic events. (Funded
      by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration
      Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).

PMID- 29226800
TI  - Waterpipe use in adolescents in Northern Sweden: Association with mental well
      being and risk and health behaviours.
AB  - AIMS: There is a lack of studies examining the association between waterpipe
      smoking and mental well-being among adolescents. This study sought to determine
      whether waterpipe smoking is associated with mental well-being and other risk and
      health behaviours in adolescents. METHODS: A questionnaire was distributed to
      1006 adolescents in grades 9-12 (with a response rate of >95%), containing
      questions on measures of stress, mental energy and sleep. In addition, the
      questionnaire assessed risk and health behaviours, including use of a waterpipe,
      cigarettes, e-cigarettes, snus, alcohol, narcotics, gambling and exercise.
      Logistic regression was used to assess factors associated with waterpipe use.
      RESULTS: Thirty-seven per cent ( n=371) of the participants had used a waterpipe
      at some point. Waterpipe use was associated with lower mental energy (odds ratio
      [OR] = 0.90, 95% confidence interval [CI] 0.81-0.99), higher stress (OR = 1.10,
      95% CI 1.02-1.20) and use of cigarettes (OR = 3.82, 95% CI 2.33-6.03), e
      cigarettes (OR = 3.26, 95% CI 2.12-4.99), snus (OR = 2.29, 95% CI 2.12-4.99),
      alcohol (OR = 1.92, 95% CI 1.07-3.44) and narcotics (OR = 3.64, 95% CI 1.75
      7.58). Waterpipe use was not significantly associated with gambling, exercise or
      sleep quality. CONCLUSIONS: Waterpipe use in adolescents is associated with worse
      mental well-being, as well as use of other nicotine products, alcohol and
      narcotics. Prospective studies are needed to delineate causal and temporal
      relationships further between waterpipe use and mental well-being and its
      relationship to other risky behaviours in order to design effective prevention
      programs.

PMID- 29226802
TI  - [In vitro oogenesis: How far have we come?]
AB  - Oogenesis is a complex cellular and molecular process whose fundamental
      mechanisms are still poorly described or not yet elucidated, especially in human
      species. The development of an in vitro model of oogenesis, particularly during
      fetal development in humans, is a critical step that would allow: (i) a better
      understand of the biological mechanisms of oogenesis; (ii) a refinement of
      medical diagnosis for women suffering from infertility; and (iii) providing new
      therapeutics for reproductive pathologies. The genesis of this model could be
      considered from ES/iPS cells. In this article, we will trace the physiological
      mechanisms of oogenesis in vivo and discuss the studies carried out in the field
      of in vitro oogenesis from ES/iPS cells, as well as the challenges to be met in
      the future.

PMID- 29226803
TI  - Quantitative Missense Variant Effect Prediction Using Large-Scale Mutagenesis
      Data.
AB  - Large datasets describing the quantitative effects of mutations on protein
      function are becoming increasingly available. Here, we leverage these datasets to
      develop Envision, which predicts the magnitude of a missense variant's molecular
      effect. Envision combines 21,026 variant effect measurements from nine large
      scale experimental mutagenesis datasets, a hitherto untapped training resource,
      with a supervised, stochastic gradient boosting learning algorithm. Envision
      outperforms other missense variant effect predictors both on large-scale
      mutagenesis data and on an independent test dataset comprising 2,312 TP53
      variants whose effects were measured using a low-throughput approach. This
      dataset was never used for hyperparameter tuning or model training and thus
      serves as an independent validation set. Envision prediction accuracy is also
      more consistent across amino acids than other predictors. Finally, we demonstrate
      that Envision's performance improves as more large-scale mutagenesis data are
      incorporated. We precompute Envision predictions for every possible single amino
      acid variant in human, mouse, frog, zebrafish, fruit fly, worm, and yeast
      proteomes (https://envision.gs.washington.edu/).

PMID- 29226805
TI  - Anaphylaxis to invasive chlorhexidine administration despite tolerance of topical
      chlorhexidine use.

PMID- 29226806
TI  - Underestimation of specific IgE measurements using extract-based assays on
      undiluted sera revealed through dilution.

PMID- 29226804
TI  - Systems Pharmacology Dissection of Cholesterol Regulation Reveals Determinants of
      Large Pharmacodynamic Variability between Cell Lines.
AB  - In individuals, heterogeneous drug-response phenotypes result from a complex
      interplay of dose, drug specificity, genetic background, and environmental
      factors, thus challenging our understanding of the underlying processes and
      optimal use of drugs in the clinical setting. Here, we use mass-spectrometry
      based quantification of molecular response phenotypes and logic modeling to
      explain drug-response differences in a panel of cell lines. We apply this
      approach to cellular cholesterol regulation, a biological process with high
      clinical relevance. From the quantified molecular phenotypes elicited by various
      targeted pharmacologic or genetic treatments, we generated cell-line-specific
      models that quantified the processes beneath the idiotypic intracellular drug
      responses. The models revealed that, in addition to drug uptake and metabolism,
      further cellular processes displayed significant pharmacodynamic response
      variability between the cell lines, resulting in cell-line-specific drug-response
      phenotypes. This study demonstrates the importance of integrating different types
      of quantitative systems-level molecular measurements with modeling to understand
      the effect of pharmacological perturbations on complex biological processes.

PMID- 29226807
TI  - Asthma, Family History of Drug Allergy, and Age Predict Amoxicillin Allergy in
      Children.
AB  - BACKGROUND: Suspected adverse reactions to amoxicillin are common, but there are
      no known factors that can predict amoxicillin allergy in children. In addition,
      methods used for the diagnosis of amoxicillin allergy are not standardized and
      their role in diagnosis is not clear. OBJECTIVE: To identify predictive factors
      and to assess the role of skin test in the diagnosis of amoxicillin allergy in
      children. METHODS: Children with a history of immediate (excluding anaphylaxis)
      or nonimmediate reactions to amoxicillin were tested by skin prick test, followed
      by oral graded challenge with amoxicillin. Clinical characteristics of the
      reaction before and after the challenge were recorded, and data of personal and
      relatives' drug allergies and atopy were collected for statistical analysis.
      RESULTS: Skin prick tests followed by an oral graded challenge with amoxicillin
      were performed on 133 children. The skin test result was not of clinical value
      because it was negative in all children. Three children (2%) had an immediate
      reaction and 7 children (5%) had a nonimmediate reaction. Asthma (odds ratio
      [OR], 0.12; 95% CI, 0.017-0.869; P = .03), family history of drug allergy (OR,
      0.12; 95% CI, 0.026-0.613; P = .01), older age at reaction (OR, 0.837; 95% CI,
      0.699-1; P = .05), and angioedema (OR, 0.22; 95% CI, 0.043-1.12; marginally
      significant at P = .069) were associated with reduced chance to pass the oral
      challenge. CONCLUSIONS: Skin prick test did not contribute to the diagnosis of
      amoxicillin allergy. The presence of asthma, family history of drug allergy, and
      older age at reaction can be used as predictive factors for true amoxicillin
      allergy in children.

PMID- 29226808
TI  - Increased Tolerance to Less Extensively Heat-Denatured (Baked) Milk Products in
      Milk-Allergic Children.
AB  - BACKGROUND: Most milk-allergic children tolerate baked milk. OBJECTIVE: To
      investigate the effect of more frequent versus less frequent introduction of
      higher doses of more allergenic (less heat-denatured) forms of milk (MAFM) on
      progression to tolerance. METHODS: Milk-allergic children were challenged with
      increasing doses of MAFM; baked foods were incorporated into the diet; challenges
      were repeated at 6- or 12-month intervals over 36 months. RESULTS: A total of 136
      children (70% males) were enrolled in the active group (median age, 7 years). At
      baseline, 41 (30%) reacted to muffin, 31 (23%) to pizza, 11 (8%) to rice pudding,
      43 (32%) to non-baked milk; and 10 (7%) tolerated non-baked milk. Children who
      tolerated baked milk but reacted to non-baked liquid milk were randomized to MAFM
      challenges every 6 months (n = 41) or 12 months (n = 44). At month 36, 61%
      children in the 6-month and 73% in the 12-month escalation groups tolerated MAFM.
      Overall, 41 (48%) children who ingested baked-milk diet became tolerant to non
      baked milk; no difference was seen between 6- and 12- month escalations. Among
      children who reacted to muffin at baseline and continued avoidance, 20% developed
      tolerance to baked milk and 0% tolerated non-baked milk. None of the 34 children
      who qualified for inclusion but chose not to take part in the active study became
      tolerant to any form of milk by history. CONCLUSIONS: Majority of children
      tolerated baked milk at baseline. Baked-milk diets were associated with
      progressive immunomodulation. Most children who incorporated baked milk into
      their diet progressed to tolerating MAFM, but there was no advantage to more
      frequent attempts to escalate to MAFM, per intention-to-treat analysis.

PMID- 29226810
TI  - Standardisation of lung function test interpretation: Global Lung Function
      Initiative.

PMID- 29226809
TI  - Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with
      Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.
AB  - BACKGROUND: While accumulating evidence suggests that vitamin D deficiency may be
      involved in the risk to develop schizophrenia and its outcome, there are no
      studies on vitamin D supplementation in this context. We sought to assess the
      effect of vitamin D supplementation on psychiatric, cognitive and metabolic
      parameters in chronic clozapine-treated schizophrenia patients. METHODS: This
      eight-week, randomized, double-blind, placebo-controlled clinical trial,
      recruited schizophrenia patients who had been maintained on clozapine treatment
      for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS
      scores >70 (to ascertain the presence of residual symptoms). Patients were
      randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo
      and subsequently assessed at two-week intervals for psychosis severity, mood,
      cognition and metabolic profile. RESULTS: Twenty four patients were randomly
      assigned to vitamin D (aged 39.4+/-9.6years, 75% males) and the other 23 patients
      to the placebo arm (aged 42.5+/-11.2years, 60.9% males). After eight weeks, the
      vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs 
      0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic,
      depressive or metabolic parameters. However, in the vitamin D group, there was a
      trend towards improved cognition (effect size=0.17, significance lost following
      Bonferroni correction). CONCLUSIONS: Vitamin D supplementation was associated
      with a trend towards improved cognition, but did not affect psychosis, mood or
      metabolic status. It is possible that the robust decrease in the PANSS scores in
      both groups may have obscured an effect of vitamin D supplementation.

PMID- 29226811
TI  - Evidence-Based Therapy and Its Association With Workforce Detachment After First
      Hospitalization for Heart Failure.
AB  - OBJECTIVES: This study investigated the association between the use of evidence
      based medicine (EBM) for heart failure (HF) and risk of workforce detachment.
      BACKGROUND: The ability to work can be a marker of functional capacity and
      quality of life. METHODS: We examined a nationwide cohort of patients in the
      workforce 1 year after first hospitalization for HF. EBM was defined as treatment
      with beta-blockers and renin angiotensin system inhibitors. The fraction of
      target dose (0 TO 1) for each drug was calculated. The sum of the fractions gave
      each patient a score between 0 and 2. Patients were stratified into 4 groups
      according to this score: group 4 score = 2 (target dose of both drugs); group 3
      score <2 to >1; group 2 score <=1 to >0.5; and group 1 score <=0.5. The risk of
      subsequent workforce detachment was estimated in cause specific Cox regression
      models. RESULTS: One year after first HF hospitalization, 10,185 patients were
      part of the workforce, and 7,561 (74%) were in treatment with at least 1 of the
      components of EBM. During a median follow-up of 727 days, 2,698 individuals (36%)
      became detached from the workforce. Patients receiving more EBM had a
      significantly lower risk of workforce detachment compared with those receiving
      less EBM (group 4 hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.77 to
      0.98; group 3 HR: 0.85; 95% CI: 0.77 to 0.94; and group 2 HR 0.92; 95% CI: 0.83
      to 1.02), all compared to group 1. CONCLUSIONS: Patients in the workforce 1 year
      after first HF hospitalization and treated with target or near-target doses of
      EBM were associated with a significantly lower risk of subsequent workforce
      detachment.

PMID- 29226812
TI  - The Right Diet for Heart Failure: Finding Morsels for Success.

PMID- 29226813
TI  - Are We Approaching Chronotropy (In)competently?

PMID- 29226814
TI  - Yet Another (Important) Goal for Heart Failure Patients.

PMID- 29226815
TI  - Integrative Assessment of Congestion in Heart Failure Throughout the Patient
      Journey.
AB  - Congestion is one of the main predictors of poor patient outcome in patients with
      heart failure. However, congestion is difficult to assess, especially when
      symptoms are mild. Although numerous clinical scores, imaging tools, and
      biological tests are available to assist physicians in ascertaining and
      quantifying congestion, not all are appropriate for use in all stages of patient
      management. In recent years, multidisciplinary management in the community has
      become increasingly important to prevent heart failure hospitalizations.
      Electronic alert systems and communication platforms are emerging that could be
      used to facilitate patient home monitoring that identifies congestion from heart
      failure decompensation at an earlier stage. This paper describes the role of
      congestion detection methods at key stages of patient care: pre-admission,
      admission to the emergency department, in-hospital management, and lastly,
      discharge and continued monitoring in the community. The multidisciplinary
      working group, which consisted of cardiologists, emergency physicians, and a
      nephrologist with both clinical and research backgrounds, reviewed the current
      literature regarding the various scores, tools, and tests to detect and quantify
      congestion. This paper describes the role of each tool at key stages of patient
      care and discusses the advantages of telemedicine as a means of providing true
      integrated patient care.

PMID- 29226816
TI  - Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide
      Formulation Administered Subcutaneously in Outpatients With Worsening Heart
      Failure.
AB  - OBJECTIVES: This study sought to determine the efficacy and safety of a novel, pH
      neutral formulation of furosemide administered subcutaneously (SC) for treatment
      of acute decompensated heart failure (HF). BACKGROUND: Congestion requiring
      intravenous (IV) administration of a diuretic agent is the main reason patients
      with HF present for acute medical care. METHODS: Outpatients presenting with
      decompensated HF were randomized to receive a single SC or IV dose of furosemide.
      Primary outcome was 6-h urine output, and secondary outcomes were weight change,
      natriuresis, and adverse events. RESULTS: Forty-one patients were randomized: 19
      were treated with IV (mean dose: 123 +/- 47 mg) and 21 with SC furosemide (fixed
      dose of 80 mg over 5 h). The 6-h urine output in the IV group was not
      significantly different from that in the SC furosemide group (median IV: 1,425
      ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR:
      900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly
      different (-1.5 +/- 1.1 kg in the IV group vs. -1.5 +/- 1.2 kg in the SC group; p
      = 0.95). Hourly urine output was significantly higher in the IV group at hour 2
      (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the
      SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005).
      Natriuresis was higher in the SC group (IV: 7.3 +/- 35.3 mEq/l vs. SC: 32.8 +/-
      43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or
      skin irritation with either formulation. Thirty-day hospitalization rates were
      similar. CONCLUSIONS: In this phase II trial, we did not identify significant
      differences between urine output obtained with pH-neutral furosemide administered
      SC and that obtained by IV. This method of decongestion may allow treatment at
      home and reduced HF resources and warrants further investigation. (Sub-Q Versus
      IV Furosemide in Acute Heart Failure; NCT02579057).

PMID- 29226817
TI  - The Twittersphere Needs Academic Cardiologists!: #heartdisease #No1Killer
      #beyondjournals.

PMID- 29226818
TI  - Rate-Response Programming Tailored to the Force-Frequency Relationship Improves
      Exercise Tolerance in Chronic Heart Failure.
AB  - OBJECTIVES: This study sought to examine whether the heart rate (HR) at which the
      force-frequency relationship (FFR) slope peaks (critical HR) could be used to
      tailor HR response in chronic heart failure (CHF) patients with cardiac
      pacemakers and whether this favorably influences exercise capacity. BACKGROUND:
      CHF secondary to left ventricular (LV) systolic dysfunction is characterized by
      blunting of the positive relationship between HR and LV contractility known as
      the FFR. METHODS: This observational study was carried out in patients with CHF
      and healthy subjects with pacemaker devices. The study assessed the 3 important
      features of the FFR (critical HR, peak contractility, and the FFR slope), and
      their reproducibility was measured noninvasively using echocardiography. The
      investigators then undertook a double-blind, randomized, controlled crossover
      study comparing the effects of tailored pacemaker rate-response programming on
      the basis of the FFR with conventional rate-response programming on exercise time
      and maximal oxygen consumption. RESULTS: The study enrolled 90 patients with CHF
      into the observational cohort study: mean age, 73.6 +/- 8.9 years; mean left
      ventricular ejection fraction (LVEF), 33.5 +/- 10.9%. The study investigated 15
      control subjects with normal LV function (LVEF, 55.6 +/- 5.3%). The critical HR
      (103 +/- 22 beats/min vs. 126 +/- 15 beats/min; p = 0.0002), peak contractility
      (3.8 +/- 3.7 SBP/LVESVI vs. 9.8 +/- 4.1 SBP/LVESVI; p = 0.0001), and the slope of
      the FFR (p < 10-15) were lower in patients with CHF than in control subjects. A
      total of 52 patients, with a mean LVEF of 32 +/- 11% on optimal therapy, took
      part in the crossover study. Rate-response settings limiting HR rise to below the
      critical HR led to greater exercise time (475 +/- 189 s vs. 425 +/- 196 s; p =
      0.003) and higher peak oxygen consumption (17.3 +/- 4.6 ml/kg/min vs. 16.6 +/-
      4.7 ml/kg/min; p = 0.01). CONCLUSIONS: A personalized approach to rate-response
      programming, determined using a reproducible noninvasive method for assessing the
      FFR, improves exercise time in patients with CHF and pacemaker devices. (Bowditch
      Revisited: Defining the Optimum Heart Rate Range in Chronic Heart Failure;
      NCT02563873).

PMID- 29226819
TI  - Adherence to Mediterranean Diet and All-Cause Mortality After an Episode of Acute
      Heart Failure: Results of the MEDIT-AHF Study.
AB  - OBJECTIVES: The authors sought to evaluate clinical outcomes of patients after an
      episode of acute heart failure (AHF) according to their adherence to the
      Mediterranean diet (MedDiet). BACKGROUND: It has been proved that MedDiet is a
      useful tool in primary prevention of cardiovascular diseases. However, it is
      unknown whether adherence to MedDiet is associated with better outcomes in
      patients who have already experienced an episode of AHF. METHODS: We designed a
      prospective study that included consecutive patients diagnosed with AHF in 7
      Spanish emergency departments (EDs). Patients were included if they or their
      relatives were able to answer a 14-point score of adherence to the MedDiet, which
      classified patients as adherents (>=9 points) or nonadherents (<=8 points). The
      primary endpoint was all-cause mortality at the end of follow-up, and secondary
      endpoints were 1-year ED revisit without hospitalization, rehospitalization,
      death, and a combined endpoint of all these variables for patients discharged
      after the index episode. Unadjusted and adjusted hazard ratios (HRs) were
      calculated. RESULTS: We included 991 patients (mean age of 80 +/- 10 years, 57.8%
      women); 523 (52.9%) of whom were adherent to the MedDiet. After a mean follow-up
      period of 2.1 +/- 1.3 years, no differences were observed in survival between
      adherent and nonadherent patients (HR of adherents [HRadh] = 0.86; 95% confidence
      interval [CI]: 0.73 to 1.02). The 1-year cumulative ED revisit for the whole
      cohort was 24.5% (HRadh = 1.10; 95% CI: 0.84 to 1.42), hospitalization 43.7%
      (HRadh = 0.74; 95% CI: 0.61 to 0.90), death 22.7% (HRadh = 1.05; 95% CI: 0.8 to
      1.38), and combined endpoint 66.8% (HRadh = 0.89; 95% CI: 0.76 to 1.04).
      Adjustment by age, hypertension, peripheral arterial disease, previous episodes
      of AHF, treatment with statins, air-room pulsioxymetry, and need for ventilation
      support in the ED rendered similar results, with no statistically significant
      differences in mortality (HRadh = 0.94; 95% CI: 0.80 to 1.13) and persistence of
      lower 1-year hospitalization for adherents (HRadh = 0.76; 95% CI: 0.62 to 0.93).
      CONCLUSIONS: Adherence to the MedDiet did not influence long-term mortality after
      an episode of AHF, but it was associated with decreased rates of
      rehospitalization during the next year.

PMID- 29226820
TI  - Furosemide Reimagined: Novel Subcutaneous Formulation for a 50-Year-Old Loop
      Diuretic Agent for the Treatment of Acute Decompensated Heart Failure.

PMID- 29226821
TI  - Patterns of civilian and child deaths due to war-related violence in Syria: a
      comparative analysis from the Violation Documentation Center dataset, 2011-16.
AB  - BACKGROUND: Since March, 2011, the Syrian civil war has lowered life expectancy
      by as much as 20 years. We describe demographic, spatial, and temporal patterns
      of direct deaths of civilians and opposition combatants from conflict-related
      violence in 6 years of war. METHODS: We analysed conflict-related violent deaths
      with complete information on date, place, and cause of death and demographic
      group occurring from March 18, 2011, to Dec 31, 2016, recorded by the Violation
      Documentation Center (VDC). We included civilian and combatant deaths in all
      Syrian governorates, excluding government-controlled areas. We did not include
      detainees and missing persons, nor deaths from siege conditions or insufficient
      medical care. We categorised deaths based on VDC weapon type. We used chi2
      testing to compare deaths from different weapons in civilian men, women, boys,
      and girls and adult and child combatants. We analysed deaths by governorate and
      over time. FINDINGS: The VDC recorded 143 630 conflict-related violent deaths
      with complete information between March 18, 2011, and Dec 31, 2016. Syrian
      civilians constituted 101 453 (70.6%) of the deaths compared with 42 177 (29.4%)
      opposition combatants. Direct deaths were caused by wide-area weapons of shelling
      and air bombardments in 58 099 (57.3%) civilians, including 8285 (74.6%) civilian
      women and 13 810 (79.4%) civilian children, and in 4058 (9.6%) opposition
      combatants. Proportions of children among civilian deaths increased from 8.9%
      (388 of 4254 civilian deaths) in 2011 to 19.0% (4927 of 25 972) in 2013 and to
      23.3% (2662 of 11 444) in 2016. Of 7566 deaths from barrel bombs, 7351 (97.2%)
      were civilians, of whom 2007 (27.3%) were children. Of 20 281 deaths by
      execution, 18 747 (92.4%) were civilians and 1534 (7.6%) were opposition
      combatants. Compared with opposition child soldiers who were male (n=333), deaths
      of civilian male children (n=11 730) were caused more often by air bombardments
      (39.2% vs 5.4%, p<0.0001) and shelling (37.3% vs 13.2%, p<0.0001) and less often
      by shooting (12.5% vs 76.0%, p<0.0001). INTERPRETATION: Aerial bombing and
      shelling rapidly became primary causes of direct deaths of women and children and
      had disproportionate lethal effects on civilians, calling into question the use
      of wide-area explosive weapons in urban areas. Increased reliance on aerial
      bombing by the Syrian Government and international partners is likely to have
      contributed to findings that children were killed in increasing proportions over
      time, ultimately comprising a quarter of civilian deaths in 2016. The inordinate
      proportion of civilians among the executed is consistent with deliberate tactics
      to terrorise civilians. Deaths from barrel bombs were overwhelmingly civilian
      rather than opposition combatants, suggesting indiscriminate or targeted warfare
      contrary to international humanitarian law and possibly constituting a war crime.
      FUNDING: None.

PMID- 29226822
TI  - Documenting deaths in the Syrian war.

PMID- 29226823
TI  - Multisensory influence on eating behavior: Hedonic consumption.
AB  - Research in obesity has traditionally focused on prevention strategies and
      treatments aimed at changing lifestyle habits. However, recent research suggests
      that eating behavior is a habit regulated not only by homeostatic mechanisms, but
      also by the hedonic pathway that controls appetite and satiety processes.
      Cognitive, emotional, social, economic, and cultural factors, as well as
      organoleptic properties of food, are basic aspects to consider in order to
      understand eating behavior and its impact on health. This review presents a
      multisensory integrative view of food at both the homeostatic and non-homeostatic
      levels. This information will be of scientific interest to determine behavior
      drivers leading to overeating and, thus, to propose effective measures, at both
      the individual and population levels, for the prevention of obesity and
      associated metabolic diseases.

PMID- 29226824
TI  - mDixon-based texture analysis of an intraosseous lipoma: a case report and
      current review for the dental clinician.
AB  - An intraosseous lipoma is a rare histologic variant of lipoma, accounting for
      only 0.1% of all primary bone tumors. This may not be the actual incidence
      because most of these lesions are frequently asymptomatic, but imaging
      modalities, such as computed tomography or magnetic resonance imaging (MRI) seem
      to have increased the detection rate. Lipoma occasionally undergoes osseous
      metaplasia and becomes an osseous lipoma. Although there are numerous papers
      discussing intraosseous lipoma and some authors have tried to differentiate
      lipomas from osseous lipomas, there is still a great deal of confusion with
      regard to characteristic radiologic features and the use of terms. Use of the
      mDixon sequence in MRI could be an effective, noninvasive method of lesion
      detection and differential diagnosis. Texture analysis is a useful technique for
      capturing intratumoral characteristics. We report what is possibly the first use
      of the mDixon MRI sequence in the measurement of tumoral texture in a case of the
      extremely rare inferior nasal turbinate intraosseous lipoma in a 58-year-old
      female. We conclude that mDixon and texture analysis are helpful methods for
      differentiating intraosseous lipomas from other masses and confirming the benign
      characteristics of lipoma. Our review of head and neck intraosseous lipoma could
      be of particular interest to head and neck surgeons and dental clinicians.

PMID- 29226826
TI  - Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across
      Radiologists.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) interpreted by
      experts is a powerful tool for diagnosing prostate cancer. However, the
      generalizability of published results across radiologists of varying expertise
      has not been verified. OBJECTIVE: To assess variability in mpMRI reporting and
      diagnostic accuracy across radiologists of varying experience in routine clinical
      care. DESIGN, SETTING, AND PARTICIPANTS: Men who underwent mpMRI and MR-fusion
      biopsy between 2014-2016. Each MRI scan was read by one of nine radiologists
      using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read
      before biopsy. Biopsy histopathology was the reference standard. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were the PIRADS score
      distribution and diagnostic accuracy across nine radiologists. We evaluated the
      association between age, prostate-specific antigen, PIRADS score, and radiologist
      in predicting clinically significant cancer (Gleason >=7) using multivariable
      logistic regression. We conducted sensitivity analyses for case volume and
      changes in accuracy over time. RESULTS AND LIMITATIONS: We analyzed data for 409
      subjects with 503 MRI lesions. While the number of lesions (mean 1.2
      lesions/patient) did not differ across radiologists, substantial variation
      existed in PIRADS distribution and cancer yield. The significant cancer detection
      rate was 3-27% for PIRADS 3 lesions, 23-65% for PIRADS 4, and 40-80% for PIRADS 5
      across radiologists. Some 13-60% of men with a PIRADS score of <3 on MRI harbored
      clinically significant cancer. The area under the receiver operating
      characteristic curve varied from 0.69 to 0.81 for detection of clinically
      significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were
      independently associated with cancer in multivariable analysis. Neither
      individual radiologist volume nor study period impacted the results. MRI scans
      were not retrospectively re-read by all radiologists, precluding measurement of
      inter-observer agreement. CONCLUSIONS: We observed considerable variability in
      PIRADS score assignment and significant cancer yield across radiologists. We
      advise internal evaluation of mpMRI accuracy before widespread adoption. PATIENT
      SUMMARY: We evaluated the interpretation of multiparametric magnetic resonance
      imaging of the prostate in routine clinical care. Diagnostic accuracy depends on
      the Prostate Imaging Reporting and Data System score and the radiologist.

PMID- 29226827
TI  - Cutaneous leishmaniasis in Senegal: a series of 38 cases at the Aristide Le
      Dantec University Hospital in Dakar.
AB  - Our aims were to study the epidemiological, clinical, and parasitological aspects
      of cutaneous leishmaniasis in the dermatology department of the Aristide Le
      Dantec hospital. This retrospective study reviewed records of cases treated over
      a 4-year period (from April 2010 through April 2014) at the HALD Dermatology
      department. The study included all patients with cutaneous leishmaniasis during
      the study period. The diagnostic criteria were clinical, parasitological, and
      histological. The study included 38 patients, corresponding to 9.5 cases per
      year. Patients' average age was 25 years (4-65 years) and the sex ratio was 1.6.
      The mean time from symptom outset to consultation was 3.2 months. The disease was
      located in limbs in 23 cases (63.8%), the face in 6 cases (16.6%), and
      disseminated in 9 (19.6%). The clinical presentation was ulcerated and crusted in
      17 patients (44.7%), sporotrichoid in 13 (28.9%), pseudo-lepromatous in 4
      (10.5%), and lupoid in 3 cases (7.9 %). It included warts, mucosa, and tropical
      sores (Aleppo boils) in all cases. We observed 3 cases associated with HIV; one
      had a pseudo-lepromatous presentation and resulted from immune restoration
      syndrome, while two patients had clinical forms of associations: ulcerative and
      crusted lesions associated with mucosal leishmaniasis in a 55-year-old patient,
      and cutaneous ulcerative, lupoid, and crusted multifocal (cutaneous, medullary,
      and lymph nodes) lesions in a 4-year-old infected with Leishmania infantum.
      Crusted ulcerative cutaneous leishmaniasis is the predominant form of cutaneous
      leishmaniasis. Infection with HIV can be an important factor in clinical and
      parasitological atypia.

PMID- 29226825
TI  - Desacetyl-alpha-melanocyte stimulating hormone and alpha-melanocyte stimulating
      hormone are required to regulate energy balance.
AB  - OBJECTIVE: Regulation of energy balance depends on pro-opiomelanocortin (POMC)
      derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating
      hormone (alpha-MSH) is the predicted natural POMC-derived peptide that regulates
      energy balance. Desacetyl-alpha-MSH, the precursor for alpha-MSH, is present in
      brain and blood. Desacetyl-alpha-MSH is considered to be unimportant for
      regulating energy balance despite being more potent (compared with alpha-MSH) at
      activating the appetite-regulating MC4R in vitro. Thus, the physiological role
      for desacetyl-alpha-MSH is still unclear. METHODS: We created a novel mouse model
      to determine whether desacetyl-alpha-MSH plays a role in regulating energy
      balance. We engineered a knock in targeted QKQR mutation in the POMC protein
      cleavage site that blocks the production of both desacetyl-alpha-MSH and alpha
      MSH from adrenocorticotropin (ACTH1-39). RESULTS: The mutant ACTH1-39 (ACTHQKQR)
      functions similar to native ACTH1-39 (ACTHKKRR) at the melanocortin 2 receptor
      (MC2R) in vivo and MC4R in vitro. Male and female homozygous mutant ACTH1-39
      (Pomctm1/tm1) mice develop the characteristic melanocortin obesity phenotype.
      Replacement of either desacetyl-alpha-MSH or alpha-MSH over 14 days into
      Pomctm1/tm1 mouse brain significantly reverses excess body weight and fat mass
      gained compared to wild type (WT) (Pomcwt/wt) mice. Here, we identify both
      desacetyl-alpha-MSH and alpha-MSH peptides as regulators of energy balance and
      highlight a previously unappreciated physiological role for desacetyl-alpha-MSH.
      CONCLUSIONS: Based on these data we propose that there is potential to exploit
      the naturally occurring POMC-derived peptides to treat obesity but this relies on
      first understanding the specific function(s) for desacetyl-alpha-MSH and alpha
      MSH.

PMID- 29226828
TI  - Cancer mortality in the urological department of the Sylvanus Olympio Teaching
      Hospital in Lome, Togo.
AB  - To determine the proportion of cancer mortality seen in the urology department of
      a teaching hospital in sub-Saharan Africa and to identify the contributing
      factors. This 10-year retrospective study took place in the urology department of
      the Sylvanus Olympio Teaching Hospital of Lome (Togo) and analyzed the records of
      patients who died of cancer from January 2006 through December 2015. During the
      study period, 94 deaths were recorded in the department, 84% of them due to a
      urological cancer. The mean age of patients was 62 years,- and there was a
      significant male predominance with a sex ratio of 4.3. Prostate cancer was the
      most common cause of death, accounting for 49 (62%) cases. The mean duration of
      symptoms was 2.4 months. At diagnosis, 75.9% of patients were metastatic and 66%
      had comorbidities, such as high blood pressure or diabetes. Palliative treatment
      was instituted for 87.3% of patients. Deterioration of their general condition
      was the immediate cause of death in 71% of cases. Urological cancers remain a
      challenge for specialists in Togo, especially because they are characterized by
      late presentation with diagnosis at the metastatic stage. Their prognosis is
      aggravated by the presence of comorbidities.

PMID- 29226829
TI  - Fertility preservation in young cancer patients as a springboard to address the
      needs of this unique population.

PMID- 29226830
TI  - Public access defibrillation: the road ahead.

PMID- 29226831
TI  - Public access defibrillation in Hong Kong in 2017.
AB  - The concept of public access defibrillation was proposed more than 20 years ago.
      Since then, various programmes have been implemented in many major cities
      although not all have been successful. Fourteen years ago, the question of
      whether Hong Kong needed public access defibrillation was raised. This article
      aimed to answer this question based on the best available evidence. Over the
      years, the clinical effectiveness of public access defibrillation in out-of
      hospital cardiac arrest has been proven. Nonetheless various studies have
      indicated that among others, cost-effectiveness, knowledge and attitudes of the
      public, and incidence of ventricular fibrillation are important factors that will
      affect the likelihood of success of such programmes. In Hong Kong, because of the
      long interval between recognition of arrest and first defibrillation, public
      access defibrillation is probably needed. To ensure the success of such a
      programme, careful planning in addition to the installation of more automated
      external defibrillators are essential.

PMID- 29226832
TI  - The current treatment landscape of irritable bowel syndrome in adults in Hong
      Kong: consensus statements.
AB  - OBJECTIVE: The estimated prevalence of irritable bowel syndrome in Hong Kong is
      6.6%. With the increasing availability of pharmacological and non-pharmacological
      treatments, the Hong Kong Advisory Council on Irritable Bowel Syndrome has
      developed a set of consensus statements intended to serve as local
      recommendations for clinicians about diagnosis and management of irritable bowel
      syndrome. PARTICIPANTS: A multidisciplinary group of clinicians constituting the
      Hong Kong Advisory Council on Irritable Bowel Syndrome-seven gastroenterologists,
      one clinical psychologist, one psychiatrist, and one nutritionist-convened on 20
      April 2017 in Hong Kong. EVIDENCE: Published primary research articles, meta
      analyses, and guidelines and consensus statements issued by different regional
      and international societies on the diagnosis and management of irritable bowel
      syndrome were reviewed. CONSENSUS PROCESS: An outline of consensus statements was
      drafted prior to the meeting. All consensus statements were finalised by the
      participants during the meeting, with 100% consensus. CONCLUSIONS: Twenty-four
      consensus statements were generated at the meeting. The statements were divided
      into four parts covering: (1) patient assessment; (2) patient's psychological
      distress; (3) dietary and alternative approaches to managing irritable bowel
      syndrome; and (4) evidence to support pharmacological management of irritable
      bowel syndrome. It is recommended that primary care physicians assume the role of
      principal care provider for patients with irritable bowel syndrome. The current
      statements are intended to guide primary care physicians in diagnosing and
      managing patients with irritable bowel syndrome in Hong Kong.

PMID- 29226833
TI  - Feasibility of short double-balloon enteroscopy-assisted endoscopic retrograde
      cholangiopancreatography in patients with surgically altered gastrointestinal
      anatomy: experience in a regional centre.

PMID- 29226834
TI  - Portomesenteric vein thrombosis following laparoscopic sleeve gastrectomy in a
      Chinese patient.

PMID- 29226835
TI  - Is it an orbital foreign body?

PMID- 29226836
TI  - Cutaneous manifestation mimicking Stevens-Johnson syndrome in a critically ill
      patient: looks similar but totally different.

PMID- 29226838
TI  - Protection of rescuers in emergency care: where does Hong Kong stand?

PMID- 29226837
TI  - Nephrolithiasis associated with the use of topiramate in children.

PMID- 29226839
TI  - Opt-in or opt-out: that is not the question.

PMID- 29226840
TI  - Challenges to the adoption of risk algorithms for colorectal cancer screening
      programmes: perspectives for future research.

PMID- 29226841
TI  - Missing key factors in nutritional assessment and bone density in children with
      eczema.

PMID- 29226842
TI  - Authors' reply: Missing key factors in nutritional assessment and bone density in
      children with eczema.

PMID- 29226843
TI  - 2-oxo-PCE: ketamine analogue on the streets.

PMID- 29226844
TI  - An intelligent 1:2 demultiplexer as an intracellular theranostic device based on
      DNA/Ag cluster-gated nanovehicles.
AB  - The logic device demultiplexer can convey a single input signal into one of
      multiple output channels. The choice of the output channel is controlled by a
      selector. Several molecules and biomolecules have been used to mimic the function
      of a demultiplexer. However, the practical application of logic devices still
      remains a big challenge. Herein, we design and construct an intelligent 1:2
      demultiplexer as a theranostic device based on azobenzene (azo)-modified and
      DNA/Ag cluster-gated nanovehicles. The configuration of azo and the conformation
      of the DNA ensemble can be regulated by light irradiation and pH, respectively.
      The demultiplexer which uses light as the input and acid as the selector can emit
      red fluorescence or a release drug under different conditions. Depending on
      different cells, the intelligent logic device can select the mode of cellular
      imaging in healthy cells or tumor therapy in tumor cells. The study incorporates
      the logic gate with the theranostic device, paving the way for tangible
      applications of logic gates in the future.

PMID- 29226845
TI  - Synthesis, structure and magnetism of the new S  =  1 kagome magnet
      NH4Ni2.5V2O7(OH)2?H2O.
AB  - Kagome antiferromagnets (KAFMs) have long been known to host exotic electronic
      states due to their strong geometric frustration, including the quantum spin
      liquid state in [Formula: see text] systems. Away from that limit, S  =  1 KAFMs
      are also predicted to host unconventional ground states such as spin nematic
      phases, but a paucity of studies on known model materials has restricted
      progress. Here, we present the crystal structure and preliminary magnetization
      measurements on the newly synthesized S  =  1 KAFM, NH4Ni2.5V2O7(OH)[Formula: see
      text]H2O, which has the three-fold symmetry of the kagome lattice but significant
      site depletion, with  ~[Formula: see text] site occupancy. Bulk magnetic data
      show clear evidence of frustration and competition between ferromagnetic and
      antiferromagnetic interactions. We propose that the magnetic Hamiltonian is
      frustrated and that anisotropic terms cause the formation of an unconventional
      ground state.

PMID- 29226846
TI  - Magneto-plasmonic Au-Coated Co nanoparticles synthesized via hot-injection
      method.
AB  - A synthetic procedure is described for the obtaining of superparamagnetic Co
      nanoparticles (NPs) via hot-injection method in the presence of sodium
      borohydride. The Co NPs obtained have an average diameter of 5.3 nm and
      saturation magnetization of 115 emu g-1. A modified Langevin equation is fitted
      to the magnetization curves using a log-normal distribution for the particle
      diameter and an effective field to account for dipolar interactions. The
      calculated magnetic diameter of the Co NPs is 0.6 nm smaller than TEM-derived
      values, implying a magnetic dead layer of 0.3 nm. The magnetic core is coated
      with Au to prevent oxidation, resulting in water-stable magneto-plasmonic Co/Au
      core/shell NPs with saturation of 71.6 emu g-1. The coating adds a localized
      surface plasmon resonance property with absorbance in the so-called 'therapeutic
      window' (690-900 nm), suitable for biomedical applications. It is suggested that
      these multifunctional NPs are distinguished as a potential platform for applied
      and fundamental research.

PMID- 29226847
TI  - Composition and diameter modulation of magnetic nanowire arrays fabricated by a
      novel approach.
AB  - Straight magnetic nanowires composed of nickel and permalloy segments having
      different diameters are synthesized using a promising approach. This approach
      involves the controlled electrodeposition of each magnetic material into
      specially designed diameter-modulated porous alumina templates. Standard alumina
      templates are exposed to pore widening followed by a protective coating of the
      pore wall with ultrathin silica and further anodization. Micromagnetic
      simulations are employed to investigate the process of magnetization reversal in
      the fabricated nanowires when the magnetic materials exchange their places in the
      thick and thin segments. It is found that the magnetization reversal occurs by
      the propagation of transverse domain wall (DW) when the thick segment is composed
      of permalloy. However, the reversal process proceeds by the propagation of vortex
      DW when permalloy is located at the thin segment.

PMID- 29226848
TI  - Adsorption of triazine herbicides from aqueous solution by functionalized
      multiwall carbon nanotubes grown on silicon substrate.
AB  - Multi-walled carbon nanotubes (MWCNTs), because of their small size and large
      available surface area, are potentially efficient sorbents for the extraction of
      water solutes. Dispersion of MWCNTs in aqueous medium is suitable to adsorb
      organic contaminants from small sample volumes, but, the recovery of the
      suspended sorbent for successive re-use represents a critical step, which makes
      this method inapplicable in large-scale water-treatment technologies. To overcome
      this problem, we proposed here MWCNTs grown on silicon supports and investigated
      on a small-volume scale their adsorption properties towards triazine herbicides
      dissolved in water. The adsorption efficiency of the supported MWCNTs has been
      tested on seven triazine herbicides, which are emerging water contaminants in
      Europe and USA, because of their massive use, persistence in soils and potential
      risks for the aquatic organisms and human health. The investigated compounds, in
      spite of their common molecular skeleton, cover a relatively large property range
      in terms of both solubility in water and hydrophilicity/hydrophobicity. The
      functionalisation of MWCNTs carried out by acidic oxidation, apart from
      increasing wettability of the material, results in a better adsorption
      performance. Increasing of functionalisation time between 17 and 60 h
      progressively increases the extraction of all seven pesticides and produces a
      moderate increment of selectivity.

PMID- 29226850
TI  - Temperature dependent infrared nano-imaging of La0.67Sr0.33MnO3 thin film.
AB  - We investigate the temperature dependence of infrared properties at nanometer
      length scales in La0.67Sr0.33MnO3 (LSMO) thin film with a thickness of 47 unit
      cells grown on SrTiO3 substrate. The infrared nano-imaging experiments were
      performed using a near-field optical microscope in conjunction with a variable
      temperature heating stage. The near-field infrared data is consistent with the
      bulk of the LSMO film undergoing the thermally-driven non-percolative second
      order transition from a metallic, ferromagnetic phase to an insulating,
      paramagnetic phase. We find persistent infrared contrast on the nanoscale that is
      independent of temperature and which we attribute to two novel phases with
      different conductivities coexisting in the vicinity of the film-substrate
      interface. These two coexisting phases at the film-substrate interface do not
      undergo the metal-insulator transition (MIT) and hence are different from the
      metallic, ferromagnetic and insulating, paramagnetic phases in the bulk of the
      film. At temperatures approaching the nominal MIT temperature, repeated scans of
      the same microscopic area at constant temperature reveal bimodal fluctuation of
      the near-field infrared amplitude. We interpret this phenomenon as slow, critical
      fluctuations of the conductivity in the bulk of the LSMO film.

PMID- 29226849
TI  - Assessment of global and local region-based bilateral mammographic feature
      asymmetry to predict short-term breast cancer risk.
AB  - This study aims to develop and test a new imaging marker-based short-term breast
      cancer risk prediction model. An age-matched dataset of 566 screening mammography
      cases was used. All 'prior' images acquired in the two screening series were
      negative, while in the 'current' screening images, 283 cases were positive for
      cancer and 283 cases remained negative. For each case, two bilateral cranio
      caudal view mammograms acquired from the 'prior' negative screenings were
      selected and processed by a computer-aided image processing scheme, which
      segmented the entire breast area into nine strip-based local regions, extracted
      the element regions using difference of Gaussian filters, and computed both
      global- and local-based bilateral asymmetrical image features. An initial feature
      pool included 190 features related to the spatial distribution and structural
      similarity of grayscale values, as well as of the magnitude and phase responses
      of multidirectional Gabor filters. Next, a short-term breast cancer risk
      prediction model based on a generalized linear model was built using an embedded
      stepwise regression analysis method to select features and a leave-one-case-out
      cross-validation method to predict the likelihood of each woman having image
      detectable cancer in the next sequential mammography screening. The area under
      the receiver operating characteristic curve (AUC) values significantly increased
      from 0.5863  +/-  0.0237 to 0.6870  +/-  0.0220 when the model trained by the
      image features extracted from the global regions and by the features extracted
      from both the global and the matched local regions (p  =  0.0001). The odds ratio
      values monotonically increased from 1.00-8.11 with a significantly increasing
      trend in slope (p  =  0.0028) as the model-generated risk score increased. In
      addition, the AUC values were 0.6555  +/-  0.0437, 0.6958  +/-  0.0290, and
      0.7054  +/-  0.0529 for the three age groups of 37-49, 50-65, and 66-87 years
      old, respectively. AUC values of 0.6529  +/-  0.1100, 0.6820  +/-  0.0353, 0.6836
      +/-  0.0302 and 0.8043  +/-  0.1067 were yielded for the four mammography
      density sub-groups (BIRADS from 1-4), respectively. This study demonstrated that
      bilateral asymmetry features extracted from local regions combined with the
      global region in bilateral negative mammograms could be used as a new imaging
      marker to assist in the prediction of short-term breast cancer risk.

PMID- 29226851
TI  - Main problems and suggested solutions for improving radiation protection in
      medicine in Ibero-American countries. Summary of an International Conference held
      in Madrid, 2016.
AB  - During the International Conference on Radiation Protection in Medicine held in
      Bonn in 2012, several areas for improvement were identified, including specific
      actions related with justification, optimization, role of manufacturers,
      radiation protection education and training, strategic research, data collection
      on medical and occupational exposures, prevention of incidents and accidents,
      radiation safety culture, risk-benefit dialogue and implementation of the
      radiation safety standards. The outcomes of the Bonn Conference were summarized
      in the so-called 'Bonn Call for Action', identifying 10 priority actions to
      enhance RP in medicine. Trying to analyse the progress in the implementation of
      this 'Call for Action' in the Ibero-American region, several international
      organizations organized the 'Ibero-American Conference on Radiation Protection in
      Medicine' (Conferencia Iberoamericana sobre Proteccion Radiologica en Medicina,
      CIPRaM) held in Madrid, in October 2016. CIPRaM was structured in eight thematic
      sessions dealing with: diagnostic and dental radiology, image guided
      interventional radiology, nuclear medicine, radiation therapy, health authorities
      and radiation protection regulators, professional associations of technologists
      and nurses, professional associations of medical physicists and radiation
      protection experts, and universities and researchers in radiation protection in
      medicine. This paper summarizes the main results of that Conference based on the
      consensus achieved about main problems, solutions, and indicators to evaluate the
      implementation of the proposed solutions.

PMID- 29226852
TI  - Divergent effect of electric fields on the mechanical property of water-filled
      carbon nanotubes with an application as a nanoscale trigger.
AB  - Polar water molecules exhibit extraordinary phenomena under nanoscale
      confinement. Through the application of an electric field, a water-filled carbon
      nanotube (CNT) that has been successfully fabricated in the laboratory is
      expected to have distinct responses to the external electricity. Here, we examine
      the effect of electric field direction on the mechanical property of water-filled
      CNTs. It is observed that a longitudinal electric field enhances, but the
      transverse electric field reduces the elastic modulus and critical buckling
      stress of water-filled CNTs. The divergent effect of the electric field is
      attributed to the competition between the axial and circumferential pressures
      induced by polar water molecules. Furthermore, it is notable that the transverse
      electric field could result in an internal pressure with elliptical distribution,
      which is an effective and convenient approach to apply nonuniform pressure on
      nanochannels. Based on pre-strained water-filled CNTs, we designed a nanoscale
      trigger with an evident and rapid height change initiated by switching the
      direction of the electric field. The reported finding provides a foundation for
      an electricity-controlled property of nanochannels filled with polar molecules
      and provides an insight into the design of nanoscale functional devices.

PMID- 29226853
TI  - Clinical and RNA expression integrated signature for urothelial bladder cancer
      prognosis.
AB  - BACKGROUND: Accumulating evidence shows that clinical factors alone are not
      adequate for predicting the survival of patients with urothelial bladder cancer
      (UBC), and many genes have been found to be associated with UBC prognosis.
      PURPOSE: The objective of this study is to develop a signature which integrates
      clinical and molecular information to predict the overall survival of UBC
      patients more accurate. MATERIALS AND METHODS: We integrated messenger RNA (mRNA)
      and microRNA (miRNA) expression profiles and the corresponding clinical data of
      402 UBC patients and 19 normal controls from The Cancer Genome Atlas. Univariate
      Cox regression followed by a multiple testing correction and an elastic net
      regulated Cox regression were adopted to identify a prognostic signature.
      RESULTS: We generated an integrated clinical-RNA signature which consisting of 3
      clinical variables, 3 protective mRNAs, 7 risky mRNAs, 2 protective miRNAs and 1
      risky miRNA. The area under the receiver operating characteristic curve of the
      integrated clinical-RNA signature was 0.802, larger than that of the clinical
      alone signature (0.709) or the RNA-alone signature (0.726). UBC patients in the
      high-risk group had a significantly shorter overall survival time compared with
      patients in the low-risk group (clinical-RNA signature, hazard ratio = 2.441).
      CONCLUSIONS: Our conclusions that we have identified an integrated clinical-RNA
      signature that was superior to the traditional clinical-alone signature for
      ascertaining the overall survival prognosis of patients with UBC. These findings
      provide some novel genes for tumor molecular biologist to further study their
      functions and mechanisms in UBC tumorigenesis and malignance, and may be useful
      for effective clinical risk management of UBC patients.

PMID- 29226854
TI  - Diagnostic and prognostic relevance of serum miR-195 in pediatric acute myeloid
      leukemia.
AB  - BACKGROUND: MicroRNA-195 acts as a tumor suppressor in a variety of cancers.
      However, its clinical significance in pediatric acute myeloid leukemia (AML)
      remains largely undefined. OBJECTIVE: To investigate the diagnostic and
      prognostic relevance of miR-195 in this malignancy. METHODS: Expression levels of
      miR-195 in peripheral blood and bone marrow samples of patients with pediatric
      AML and normal controls were detected by real-time quantitative PCR. Then,
      receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and
      Cox regression analysis were performed to evaluate the diagnostic and prognostic
      relevance of serum miR-195 in pediatric AML. RESULTS: Compared to normal
      controls, the expression levels of miR-195 in both bone marrow and patients' sera
      were significantly decreased (both P< 0.001). In addition, serum miR-195 had an
      optimal diagnostic cut-off point (2.09) for pediatric AML with sensitivity of
      68.87% and specificity of 96.23%. The area under the ROC curve (AUC) based on
      serum miR-195 was 0.910. Moreover, patients with low serum miR-195 level more
      often had French-American-British classification subtype M7 (P= 0.02),
      unfavorable karyotypes (P= 0.01), and shorter relapse-free and overall survivals
      (both P= 0.001) than those with high serum miR-195 level. Furthermore, the
      multivariate analysis identified serum miR-195 level as an independent prognostic
      factor for both relapse-free and overall survivals. CONCLUSION: The findings of
      this study suggest that the aberrant expression of miR-195 may play crucial roles
      in the development and progression of pediatric AML patients. Serum miR-195 may
      serve as a promising marker for monitoring the occurrence of this disease and
      predicting the clinical outcome of patients.

PMID- 29226855
TI  - Knockdown of long noncoding RNA FGFR3- AS1 induces cell proliferation inhibition,
      apoptosis and motility reduction in bladder cancer.
AB  - OBJECTIVES: To study the expression pattern of long non-coding RNA FGFR3
      antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition,
      apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer.
      METHODS: The differential expression levels of FGFR3-AS1 and FGFR3 in tumor
      tissues and paired normal tissues were determined using Real-Time qPCR in a total
      of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson's
      coefficient correlation was used for expression correlation assay. Expression
      differences of FGFR3-AS1 were analyzed according to grading and staging. FGFR3
      protein was detected by western blot assay. Human bladder cancer T24 and 5637
      cell lines were transiently transfected with FGFR3-AS1-specific siRNA or negative
      control siRNA. The cell proliferation changes of transfected bladder cancer cells
      were determined using CCK-8 assay. Apoptosis caused by knockdown of FGFR3-AS1 was
      evaluated using ELISA assay. Motility changes induced by knockdown of FGFR3-AS1
      were measured using wound healing assay and transwell assay. RESULTS: Both FGFR3
      AS1 and FGFR3 were overexpressed in bladder cancer tissues compared to matched
      normal tissues. They were also positively expressed in bladder cancer. FGFR3-AS1
      expression levels were higher in high grade tumors than those in low grade
      tumors. FGFR3-AS1 expression levels were higher in invasive tumors than those in
      non-invasive tumors. Cell proliferation inhibition, increased apoptosis, and
      decreased motility were observed in FGFR3-AS1 siRNA-transfected T24 and 5637 cell
      lines. CONCLUSIONS: FGFR3-AS1 plays an oncogenic role in human bladder cancer.
      Knockdown of FGFR3-AS1 may provide a potential new therapeutic approach to this
      disease.

PMID- 29226856
TI  - Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its
      receptor PROKR2 are associated to human colorectal cancer progression and
      peritoneal carcinomatosis.
AB  - BACKGROUND: The highest risk factor for mortality among malignant tumors is
      metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF)
      is an angiogenic factor which biological activity is mediated via two G protein
      coupled receptors, prokineticin receptor1 (PROKR1) and PROKR2. Recent studies
      suggested that EG-VEGF expression is deregulated in multiple cancers including
      colorectal cancer (CRC). METHODS: Using distinctive CRC and peritoneal
      carcinomatosis (PC) cohorts and a corresponding control cohort, we determined the
      circulating levels of EG-VEGF and its in situ expression, and that of its related
      receptors. RESULTS: Circulating EG-VEGF levels were significantly increased in
      patients with metastatic PC compared to CRC and control patients (p< 0.05).
      Furthermore, according to clinicopathologic examinations, local EG-VEGF
      expression correlated with higher tumor and nodal stages (p< 0.001) of CRC. EG
      VEGF and PROKR2 were highly expressed in colorectal primary lesions compared to
      positive controls. PROKR1 expression was lower and did not change in tumor
      specimens. Also, EG-VEGF and its receptor PROKR2 were differentially expressed in
      the colorectal primary lesions and in the control groups. CONCLUSION: Altogether
      these findings suggest that EG-VEGF/receptors system might be an important actor
      in the CRC progression into PC and might be involved in the ability of tumor
      cells to invade other organs. Circulating EG-VEGF could be proposed as a
      prognostic marker in human CRC and its progression into PC.

PMID- 29226857
TI  - Prostate cancer detection using machine learning techniques by employing
      combination of features extracting strategies.
AB  - Prostate is a second leading causes of cancer deaths among men. Early detection
      of cancer can effectively reduce the rate of mortality caused by Prostate cancer.
      Due to high and multiresolution of MRIs from prostate cancer require a proper
      diagnostic systems and tools. In the past researchers developed Computer aided
      diagnosis (CAD) systems that help the radiologist to detect the abnormalities. In
      this research paper, we have employed novel Machine learning techniques such as
      Bayesian approach, Support vector machine (SVM) kernels: polynomial, radial base
      function (RBF) and Gaussian and Decision Tree for detecting prostate cancer.
      Moreover, different features extracting strategies are proposed to improve the
      detection performance. The features extracting strategies are based on texture,
      morphological, scale invariant feature transform (SIFT), and elliptic Fourier
      descriptors (EFDs) features. The performance was evaluated based on single as
      well as combination of features using Machine Learning Classification techniques.
      The Cross validation (Jack-knife k-fold) was performed and performance was
      evaluated in term of receiver operating curve (ROC) and specificity, sensitivity,
      Positive predictive value (PPV), negative predictive value (NPV), false positive
      rate (FPR). Based on single features extracting strategies, SVM Gaussian Kernel
      gives the highest accuracy of 98.34% with AUC of 0.999. While, using combination
      of features extracting strategies, SVM Gaussian kernel with texture +
      morphological, and EFDs + morphological features give the highest accuracy of
      99.71% and AUC of 1.00.

PMID- 29226858
TI  - The clinical significance of the combined detection of serum Smac, HE4 and CA125
      in endometriosis-associated ovarian cancer.
AB  - OBJECTIVE: This study aims to investigate the clinical significance of serum
      Smac, HE4 and CA125 alone or combined for detecting endometriosis-associated
      ovarian cancer (EAOC). METHODS: The level of serum Smac, HE4 and CA125 in 40
      healthy controls, 40 cases of benign endometriosis ovarian tumor, and 60 cases of
      EAOC were detected by ELISA and electrochemical immune method. RESULTS: Serum
      Smac expression level was significantly lower in the EAOC group than in the
      control group and benign ovarian tumor group (P< 0.05), while HE4 and CA125
      expression levels were significantly higher in the EAOC group than the other two
      groups. The sensitivity of Smac single detection was up to 91.67%, and the
      specificity of HE4 was up to 98.75%. Furthermore, the sensitivity of Smac + HE4 +
      CA125 combined was the highest, which reached up to 98.33%; but the specificity
      was low, which reached up to 75%. The serum expression level differences before
      and after surgery were statistically significant. As the number of chemotherapies
      increases, the Smac level increased, and HE4 and CA125 levels gradually
      decreased. Furthermore, Smac increased to normal at the end of the 2nd period of
      chemotherapy, while HE4 and CA125 decreased to normal in 2nd and 3rd period of
      chemotherapy, respectively. CONCLUSION: Serum Smac, HE4 and CA125 may play an
      important role in predicting EAOC and in monitoring the prognosis of
      postoperative EAOC.

PMID- 29226860
TI  - A hybrid multiscale model for investigating tumor angiogenesis and its response
      to cell-based therapy.
AB  - Angiogenesis, a formation of blood vessels from an existing vasculature, plays a
      key role in tumor growth and its progression into cancer. The lining of blood
      vessels consists of endothelial cells (ECs) which proliferate and migrate,
      allowing the capillaries to sprout towards the tumor to deliver the needed
      oxygen. Various treatments aiming to suppress or even inhibit angiogenesis have
      been explored. Mesenchymal stem cells (MSCs) have recently been undergoing
      development in cell-based therapy for cancer due to their ability to migrate
      towards the capillaries and induce the apoptosis of the ECs, causing capillary
      degeneration. However, further investigations in this direction are needed as it
      is usually difficult to preclinically assess the efficacy of such therapy. We
      develop a hybrid multiscale model that integrates molecular, cellular, tissue and
      extracellular components of tumor system to investigate angiogenesis and tumor
      growth under MSC-mediated therapy. Our simulations produce angiogenesis and
      vascular tumor growth profiles as observed in the experiments. Furthermore, the
      simulations show that the effectiveness of MSCs in inducing EC apoptosis is
      density dependent and its full effect is reached within several days after MSCs
      application. Quantitative agreements with experimental data indicate the
      predictive potential of our model for evaluating the efficacy of cell-based
      therapies targeting angiogenesis.

PMID- 29226859
TI  - Identification of mannose receptor and CD163 as novel biomarkers for colorectal
      cancer.
AB  - The aim of present study was to investigate the clinical significances of mannose
      receptor (MR) and CD163 in colorectal cancer (CRC). Enzyme-linked immunosorbent
      assay (ELISA) and immunohistochemistry (IHC) were utilized for this analysis.
      Preoperative serum MR and CD163 levels ranged from 0.153 to 0.804 MUg/ml (median
      = 0.359 MUg/ml) and from 0.319 to 1.314 MUg/ml (median = 0.685 MUg/ml) in CRC
      patients respectively. Strikingly, preoperative serum levels of MR and CD163 were
      significantly increased in CRC patients than in healthy individuals (P< 0.0001).
      ROC analyses suggested that the optimum diagnostic cut-offs for serum MR and
      CD163 were 0.3485 MUg/ml (AUC 0.7205, sensitivity 54.82%, and specificity 80.46%)
      and 0.6111 MUg/ml (AUC 0.7463, sensitivity 62.65%, and specificity 80.46%)
      respectively. Detection of serum MR and CD163 together obviously enhanced the
      diagnostic accuracy (AUC 0.7968, sensitivity 69.28%, and specificity 77.01%).
      Then, preoperative serum MR and CD163 levels correlated significantly with serum
      CEA, CA19-9 and CA72-4 concentrations in CRC patients (P< 0.05). High MR and
      CD163 expression in serum was associated significantly with shorter overall
      survival (P< 0.05) and demonstrated as adversely prognostic factors (P< 0.05).
      Further, expression of MR and CD163 in CRC tissues was significantly higher than
      that in para-cancer tissues (P< 0.001). High expression of MR and CD163 in CRC
      tissues also correlated significantly with shorter overall survival (P< 0.05). MR
      and CD163 expression in serum or CRC tissues all correlated positively with the
      degree of lymphatic metastasis (P< 0.0001). In conclusion, MR and CD163 may be
      novel biomarkers for CRC patients.

PMID- 29226861
TI  - Neuroanatomical Comparison of the "Word" and "Picture" Versions of the Free and
      Cued Selective Reminding Test in Alzheimer's Disease.
AB  - Episodic memory tests with cued recall, such as the Free and Cued Selective
      Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal
      atrophy contributions to memory performance in Alzheimer's disease (AD). Both
      Word and Picture versions of the test exist but show different profiles, with the
      Picture version usually scoring higher across different cohorts. One possible
      explanation for this divergent performance between the different modality
      versions of the test might be that they rely on different sets of neural
      correlates. The current study explores this by contrasting the neural correlates
      of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM)
      in AD and healthy subjects. We predicted that the Picture version would be
      associated with different cortical regions than the Word version, which might be
      more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD
      patients exhibited impairments on both versions of the FCSRT and both groups
      performed higher in the Picture version. A region of interest analysis based on
      prior work revealed significant correlations between free recall of either
      version with atrophy of the temporal pole and hippocampal regions. Thus, contrary
      to expectations, performance on both the Word and the Picture version of the
      FCSRT is associated with largely overlapping networks. Free recall is associated
      with hippocampal volume and might be properly considered as an indicator of
      hippocampal structural integrity.

PMID- 29226862
TI  - The Rationale and Design of the Reducing Pathology in Alzheimer's Disease through
      Angiotensin TaRgeting (RADAR) Trial.
AB  - BACKGROUND: Anti-hypertensives that modify the renin angiotensin system may
      reduce Alzheimer's disease (AD) pathology and reduce the rate of disease
      progression. OBJECTIVE: To conduct a phase II, two arm, double-blind, placebo
      controlled, randomized trial of losartan to test the efficacy of Reducing
      pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR). METHODS:
      Men and women aged at least 55 years with mild-to-moderate AD will be randomly
      allocated 100 mg encapsulated generic losartan or placebo once daily for 12
      months after successful completion of a 2-week open-label phase and 2-week
      placebo washout to establish drug tolerability. 228 participants will provide at
      least 182 subjects with final assessments to provide 84% power to detect a 25%
      difference in atrophy rate (therapeutic benefit) change over 12 months at an
      alpha level of 0.05. We will use intention-to-treat analysis, estimating between
      group differences in outcomes derived from appropriate (linear or logistic)
      multivariable regression models adjusting for minimization variables. RESULTS:
      The primary outcome will be rate of whole brain atrophy as a surrogate measure of
      disease progression. Secondary outcomes will include changes to 1) white matter
      hyperintensity volume and cerebral blood flow; 2) performance on a standard
      series of assessments of memory, cognitive function, activities of daily living,
      and quality of life. Major assessments (for all outcomes) and relevant safety
      monitoring of blood pressure and bloods will be at baseline and 12 months.
      Additional cognitive assessment will also be conducted at 6 months along with
      safety blood pressure and blood monitoring. Monitoring of blood pressure, bloods,
      and self-reported side effects will occur during the open-label phase and during
      the majority of the post-randomization dispensing visits. CONCLUSION: This study
      will identify whether losartan is efficacious in the treatment of AD and whether
      definitive Phase III trials are warranted.

PMID- 29226863
TI  - Associations between Use of Specific Analgesics and Concentrations of Amyloid
      beta 42 or Phospho-Tau in Regions of Human Cerebral Cortex.
AB  - Analgesics are commonly used by older adults, raising the question of whether
      their use might contribute to dementia risk and neuropathologic changes of
      Alzheimer's disease (AD). The Adult Changes in Thought (ACT) study is a
      population-based study of brain aging and incident dementia among people 65 years
      or older who are community dwelling and not demented at entry. Amyloid-beta
      (Abeta)42 and phospho-tau were quantified using Histelide in regions of cerebral
      cortex from 420 brain autopsies. Total standard daily doses of prescription
      opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure
      during a defined 10-year exposure window were identified using automated pharmacy
      dispensing data and used to classify people as having no/low, intermediate, or
      high exposure. People with high NSAID exposure had significantly greater Abeta42
      concentration in middle frontal gyrus and superior and middle temporal gyri, but
      not inferior parietal lobule; no Abeta42 regional concentration was associated
      with prescription opioid usage. People with high opioid usage had significantly
      greater concentration of phospho-tau in middle frontal gyrus than people with
      little-to-no opioid usage. Consistent with our previous studies, findings suggest
      that high levels of NSAID use in older individuals may promote Abeta42
      accumulation in cerebral cortex.

PMID- 29226864
TI  - Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild
      Cognitive Impairment.
AB  - BACKGROUND: Mounting evidence showed the self-reported levels of physical
      activity are positively associated with white matter (WM) integrity and cognitive
      performance in normal adults and patients with mild cognitive impairment (MCI).
      However, the objective measure of cardiorespiratory fitness (CRF) was not used in
      these studies. OBJECTIVE: To determine the associations of CRF measured by
      maximal oxygen uptake (VO2max) with WM fiber integrity and neurocognitive
      performance in older adults with MCI. METHODS: Eighty-one participants (age =
      65+/-7 years, 43 women), including 26 cognitively normal older adults and 55
      amnestic MCI patients, underwent VO2max test to measure CRF, diffusion tensor
      imaging (DTI) to assess WM fiber integrity, and neurocognitive assessment focused
      on memory and executive function. DTI data were analyzed by the tract-based
      spatial statistics and region-of-interest approach. RESULTS: Cognitively normal
      older adults and MCI patients were not different in global WM fiber integrity and
      VO2max. VO2max was associated positively with DTI metrics of fractional
      anisotropy in ~54% WM fiber tracts, and negatively with mean and radial
      diffusivities in ~46% and ~56% of the WM fiber tracts. The associations of VO2max
      with DTI metrics remained statistically significant after adjustment of age, sex,
      body mass index, WM lesion burden, and MCI status. The DTI metrics obtained from
      the area that correlated to VO2max were associated with executive function
      performance in MCI patients. CONCLUSIONS: Higher levels of CRF are associated
      with better WM fiber integrity, which in turn is correlated with better executive
      function performance in MCI patients.

PMID- 29226865
TI  - SIRT1 Deacetylates SC35 and Suppresses Its Function in Tau Exon 10 Inclusion.
AB  - Approximately equal amounts of 3R-tau and 4R-tau resulting from alternative
      splicing of tau exon 10 is necessary to maintain normal brain function.
      Dysregulation of alternative splicing of tau exon 10 and the imbalance of 3R
      tau/4R-tau have been seen in inherited and sporadic tauopathies. Splicing factor
      SC35 (also name as SRSF2) plays an important role in promoting tau exon 10
      inclusion. SC35 is post-translationally modified by phosphorylation and
      acetylation, but the role of acetylation in SC35-medicated tau exon 10 inclusion
      is unknown. Sirtuin type 1 (SIRT1) is an enzyme that deacetylates proteins and
      associates with age-related disease such as Alzheimer's disease. In the present
      study, we determined the role of SIRT1 in SC35 acetylation and in the alternative
      splicing of tau exon 10. We found that SIRT1 interacts with and deacetylates
      SC35, and inhibits SC35-promoted tau exon 10 inclusion. Substituting K52 residue
      of SC35 by arginine impairs the role of SC35 in tau exon 10 inclusion. These
      results suggest that SIRT1 may serve as a therapeutic target for tauopathy by
      regulating SC35-mediated tau exon 10 splicing.

PMID- 29226866
TI  - 11C-CFT-PET in Presymptomatic FTDP-17: A Potential Biomarker Predicting Onset.
AB  - Frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17) is a
      rare autosomal dominant neurodegenerative disorder. Most patients with FTDP-17
      carry the mutation in the microtubule-associated protein tau (MAPT) gene.
      Striatum is predominantly and early affected in FTDP-17. Five family members (two
      symptomatic patients and three presymptomatic mutation carriers) from a Chinese
      pedigree of FTDP-17 with N279K mutation in MAPT were enrolled. Parkinsonism was
      the initial symptom for symptomatic patients. 2b-carbomethoxy-3b-(4
      trimethylstannylphenyl) tropane (11C-CFT) uptake was obviously affected in the
      putamen of two presymptomatic mutation carriers. Presymptomatic case 3, whose 11C
      CFT uptake in the right putamen was normal at baseline, was still free of
      parkinsonism during follow-up. In conclusion, 11C-CFT-positron emission
      tomography could be a potential biomarker for the presymptomatic stage of FTDP-17
      to predict the disease onset.

PMID- 29226867
TI  - An Objective Method to Accurately Measure Cardiorespiratory Fitness in Older
      Adults Who Cannot Satisfy Widely Used Oxygen Consumption Criteria.
AB  - Cardiorespiratory fitness (CRF) is routinely investigated in older adults;
      however, the most appropriate CRF measure to use for this population has received
      inadequate attention. This study aimed to 1) evaluate the reliability and
      validity of the oxygen uptake efficiency slope (OUES) as a sub-maximal
      measurement of CRF; 2) examine demographic, risk-factor, and exercise testing
      differences in older adults who satisfied standardized criteria for a peak oxygen
      consumption (VO2peak) test compared to those who did not; and 3) determine the
      difference between directly measured VO2peak values and OUES-predicted VO2peak
      values. One hundred ten enrollees from the Wisconsin Registry for Alzheimer's
      Prevention participated in this study. Participants performed a graded maximal
      exercise test and wore an accelerometer for 7 days. For each participant, the
      OUES was calculated at 75%, 90%, and 100% of exercise duration. VO2peak was
      recorded at peak effort, and one week of physical activity behavior was measured.
      OUES values calculated at separate relative exercise durations displayed
      excellent reliability (ICC = 0.995; p < 0.001), and were strongly correlated with
      VO2peak (rrange = 0.801-0.909; p < 0.001). As hypothesized, participants who did
      not satisfy VO2peak criteria were significantly older than those who satisfied
      criteria (p = 0.049) and attained a directly measured VO2peak that was 2.31
      mL.kg.min-1 less than the value that was predicted by OUES VO2peak (p = 0.003).
      Older adults are less likely to satisfy VO2peak criteria, which results in an
      underestimation of their CRF. Without adhering to standardized criteria, VO2peak
      measurement error may lead to misinterpretation of CRF and age-related
      associations. Here, we conclude that OUES is a reliable, valid measurement of CRF
      which does not require achievement of standardized criteria.

PMID- 29226869
TI  - The Heritability of Frontotemporal Lobar Degeneration: Validation of Pedigree
      Classification Criteria in a Northern Italy Cohort.
AB  - A large portion of frontotemporal lobar degeneration (FTLD) patients has a family
      history of disease and the presence of a pathogenic mutation confirms the
      clinical diagnosis. Recently, standardized criteria to evaluate FTLD pedigree,
      based on first- and second-degree affected relatives, their age at onset, and
      clinical phenotype, were proposed and validated in an American cohort. Herein we
      applied these criteria to 402 Italian FTLD pedigrees and assessed mutation
      frequencies in GRN, C9orf72, and MAPT genes with the aim of validating these
      criteria. Moreover, we evaluated whether genetic counseling requests reflect the
      estimated family risk. 12.4% of pedigrees had high family history, 6.5% medium,
      15.4% low; 39% were apparent sporadic cases and 26.6% had family history of
      unknown significance. Mutations frequencies were in line with the categorization
      proposed: the highest rate was found in the most at-risk families (74%) and
      decreased in other categories (medium: 15.4%; low: 9.7%; sporadic: 1.3%).
      Mutation carriers with unknown family history (5.6%) were mostly early-onset
      patients. Detected mutation frequency was comparable with the US-cohort (13.7%),
      but mutations distribution among genes was different, with higher frequency of
      GRN mutations (9.4%) in our cohort. An elevated proportion of FTLD patients
      belonging to "high risk" pedigrees asked for genetic counseling (42%); requests
      decreased according to the estimated family risk (medium: 26.9%; low: 17.7%;
      sporadic: 5.1%). In conclusion, the proposed pedigree classification criteria,
      herein further validated, should be incorporated in the FTLD diagnostic work-up.
      Moreover, our data suggest to extend genetic screening to early-onset patients
      with unknown family history.

PMID- 29226868
TI  - Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down
      Syndrome.
AB  - BACKGROUND: People with Down syndrome (DS) are an ultra-high risk population for
      Alzheimer's disease (AD). Understanding the factors associated with age of onset
      and survival in this population could highlight factors associated with
      modulation of the amyloid cascade. OBJECTIVE: This study aimed to establish the
      typical age at diagnosis and survival associated with AD in DS and the risk
      factors associated with these. METHODS: Data was obtained from the Aging with
      Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting
      of data extracted from clinical records of patients seen by Community
      Intellectual Disability Services (CIDS) in England. Survival times when
      considering different risk factors were calculated. RESULTS: The mean age of
      diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78
      years, and median age at death was approximately 60 years. Survival time was
      associated with age of diagnosis, severity of intellectual disability, living
      status, anti-dementia medication status, and history of epilepsy. Age at
      diagnosis and treatment status remained predictive of survival time following
      adjustment. CONCLUSION: This study provides the best estimate of survival in
      dementia within the DS population to date, and is in keeping with previous
      estimates from smaller studies in the DS population. This study provides
      important estimates and insights into possible predictors of survival and age of
      diagnosis of AD in adults with DS, which will inform selection of participants
      for treatment trials in the future.

PMID- 29226870
TI  - Alzheimer's Disease Progression: Factors Influencing Cognitive Decline.
AB  - BACKGROUND: Alzheimer's disease (AD) patients present high variability in the
      rate of cognitive decline. Despite the wide knowledge on factors influencing
      dementia risk, little is known on what accounts for AD progression. Previous
      studies on this topic have mainly analyzed each factor separately without taking
      into account the interaction between genetic and non-genetic factors. OBJECTIVE:
      The aim of the present study is to evaluate the role of demographic, clinical,
      therapeutic, and genetic factors and their interaction on cognitive decline among
      newly diagnosed AD patients. METHODS: We retrospectively selected 160 AD patients
      diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We
      evaluated the occurrence of rapid cognitive changes defined as the worsening of
      more than four points at the Mini-Mental State Examination after 2-year follow up
      period. RESULTS: Among the 160 AD patients, 50% presented rapid disease
      progression. Extrapyramidal signs at disease onset were predictors of worse
      outcome (OR 2.2), especially among Apolipoprotein E (APOE) E4 allele carriers,
      while the presence of family history for dementia decreased the risk of rapid
      progression by about 50%. Higher educated E4-carriers showed a slower AD
      progression. We identified the chronic use of aspirin as potential secondary
      preventative strategy for the non E4-carriers. CONCLUSION: At dementia onset,
      some clinical and demographic data can be predictors of future progression. The
      outcomes of the present study support the already hypothesized interaction
      between genetic and non-genetic factors during disease course and suggest genetic
      based approaches.

PMID- 29226871
TI  - Increased Serum Acylated Ghrelin Levels in Patients with Mild Cognitive
      Impairment.
AB  - Ghrelin is a stomach-derived circulating hormone. In addition to its function as
      an orexigenic stimulant, the role of ghrelin in the consolidation of learning and
      memory has been implicated in recent years. However, the status of circulating
      acylated ghrelin (AG, that is, the functional form of ghrelin) in the symptomatic
      predementia stage of Alzheimer's disease (AD) has rarely been investigated. In
      the current study, we examined the serum levels of acylated and total ghrelin in
      22 patients with mild cognitive impairment (MCI) and 30 cognitively normal
      controls. We have found that patients with MCI had significantly increased serum
      AG levels, which were inversely associated with defected short- and long-term
      memory as well as language skills. Of note, the levels of total circulating
      ghrelin were similar between the two groups. Intriguingly, serum AG but not total
      ghrelin was associated with AD risk factors including the age, hypertension, and
      hyperlipidemia. Therefore, circulating AG may serve as a potential early systemic
      biomarker for AD-related cognitive impairments. Nevertheless, the simplest
      interpretation of the results is that the levels of circulating AG are associated
      with cognitive impairments in patients with MCI, thereby forming the groundwork
      for our future studies on the systemic mechanisms of AD pertaining to the ghrelin
      system.

PMID- 29226872
TI  - While I Still Remember: 30 Years of Alzheimer's Disease Research.
AB  - Turns out I have been a major contributor to the Journal of Alzheimer's Disease
      over its 20-year history. As such, I was invited to provide a review of my work
      over the years. What follows is a retrospective of how the Alzheimer-related
      research of a Ph.D. (i.e., not an M.D.) transitioned from basic to clinical, and
      moved from bench to bedside and back again.I have included some of the more
      humorous and poignant twists along the way that some older players may find
      familiar and I hope might inspire some younger players to hang in there.

PMID- 29226874
TI  - Alterations in Acrolein Metabolism Contribute to Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early
      diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of
      lipid peroxidation, has been shown to contribute to the pathological process of
      AD. This study recruited 118 elderly subjects consisting of 58 non-demented
      control subjects and 62 AD patients. We analyzed the acrolein-related metabolites
      in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found
      that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p =
      0.00012) and CSF (p = 0.00161) of AD patients were significantly higher than
      those of control subjects, whereas the levels of a urinary acrolein metabolite, 3
      hydroxypropyl mercapturic acid (3-HPMA), were markedly decreased (p = 0.00882) in
      AD patients. These data suggest that deregulated acrolein metabolism may be
      correlated with neuronal damage in AD patients, which might provide further
      insights into the disease progression and early diagnosis of AD.

PMID- 29226875
TI  - VEGFR1 and VEGFR2 in Alzheimer's Disease.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite
      upregulation of VEGF in the brain in Alzheimer's disease (AD), probably in
      response to amyloid-beta, vasoconstriction, and tissue hypoxia, there is no
      consequent increase in microvessel density. VEGF binds to and activates VEGF
      receptor 2 (VEGFR2), but also binds to VEGF receptor 1 (VEGFR1), which exists in
      less-active membrane-bound and inactive soluble (sVEGFR1) forms and inhibits pro
      angiogenic signaling. We have investigated whether altered expression of VEGF
      receptors might account for the lack of angiogenic response to VEGF in AD. We
      assessed the cellular distribution and protein level of VEGFR1 and VEGFR2 in
      parietal cortex from 50 AD and 36 age-matched control brains, and related the
      findings to measurements of VEGF and von Willebrand factor level (a marker of
      microvessel density) in the same tissue samples. VEGFR2 was expressed by neurons,
      astrocytes and endothelial cells. VEGFR1 was expressed predominantly neuronally
      and was significantly reduced in AD (p = 0.02). Western blot analysis on a subset
      of brains showed reduction in VEGFR1:sVEGFR1 in AD (p = 0.046). The lack of
      angiogenesis despite cerebral hypoperfusion in AD is not explained by altered
      expression of VEGFR2 or total VEGFR1; indeed, the downregulation of VEGFR1 may
      represent a pro-angiogenic response to the hypoperfusion. However, the relative
      increase in sVEGFR1 would be expected to have an anti-angiogenic effect which may
      be a factor in AD.

PMID- 29226873
TI  - Modeling Prion-Like Processing of Tau Protein in Alzheimer's Disease for
      Pharmaceutical Development.
AB  - Following our discovery of a fragment from the repeat domain of tau protein as a
      structural constituent of the PHF-core in Alzheimer's disease (AD), we developed
      an assay that captured several key features of the aggregation process. Tau-tau
      binding through the core tau fragment could be blocked by the same
      diaminophenothiazines found to dissolve proteolytically stable PHFs isolated from
      AD brain. We found that the PHF-core tau fragment is inherently capable of auto
      catalytic self-propagation in vitro, or "prion-like processing", that has now
      been demonstrated for several neurodegenerative disorders. Here we review the
      findings that led to the first clinical trials to test tau aggregation inhibitor
      therapy in AD as a way to block this cascade. Although further trials are still
      needed, the results to date suggest that a treatment targeting the prion-like
      processing of tau protein may have a role in both prevention and treatment of AD.

PMID- 29226876
TI  - Serum C-Peptide, Visfatin, Resistin, and Ghrelin are Altered in Sporadic and GRN
      Associated Frontotemporal Lobar Degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative
      disease characterized by progressive deterioration of the frontal and anterior
      temporal lobes of the brain resulting in different heterogeneous conditions,
      mainly characterized by personality changes, behavioral disturbances, such as
      binge eating, and deficits in language and executive functions. Null mutations in
      progranulin gene (GRN) are one of the most frequent genetic determinants in
      familial frontotemporal dementia. Recently, progranulin was recognized as an
      adipokine involved in diet-induced obesity and insulin resistance revealing its
      metabolic function. Increasing evidence suggests that neurodegenerative dementias
      are associated with a higher prevalence of metabolic changes than in the general
      population. According to these findings, the aim of this study is to investigate
      putative alterations in markers linked to metabolic functions (i.e., C-peptide,
      ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1,
      glucagon, insulin, resistin, and three adipokines as visfatin, leptin, and
      plasminogen activator inhibitor-1 total) in sporadic and GRN-related FTLD. We
      found that 1) C-peptide is increased in sporadic and GRN-mutated FTLD patients;
      in addition, we demonstrated an anticipation of the disease in patients with the
      highest C-peptide concentrations; 2) visfatin is slightly reduced in the whole
      FTLD group; 3) resistin, an adipokine involved in inflammatory-related diseases,
      is specifically increased in FTLD due to GRN null mutations; 4) ghrelin
      concentration is specifically increased in pre-symptomatic subjects and FTLD
      patients with GRN mutations. These findings support the hypothesis that
      alterations in metabolic pattern are involved in FTLD progression highlighting
      novel putative targets for the development of preventive and personalized
      therapies.

PMID- 29226878
TI  - ASIC1a contributes to the symptom of pain in a rat model of chronic prostatitis.
AB  - This study aims to validate our hypothesis that acid-sensing ion channels (ASICs)
      may contribute to the symptom of pain in patients with chronic prostatitis (CP).
      We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn
      neurons for further studies. ASIC1a was knocked down and its effects on the
      expression of neurogenic inflammation-related factors in the dorsal horn neurons
      of rat spinal cord were evaluated. The effect of ASIC1a on the Ca2+ ion
      concentration in the dorsal horn neurons of rat spinal cord was measured by the
      intracellular calcium ([Ca2+]i) intensity. The effect of ASIC1a on the
      p38/mitogen-activated protein kinase (MAPK) signaling pathway was also
      determined. ASIC1a was significantly upregulated in the CP rat model as compared
      with control rats. Acid-induced ASIC1a expression increased [Ca2+]i intensity in
      the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of
      neurogenic inflammation-related factors and p-p38 expression in the acid-treated
      dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the
      expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and
      pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly
      decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed
      that ASIC1a may contribute to the symptom of pain in patients with CP, at least
      partially, by regulating the p38/MAPK signaling pathway.

PMID- 29226877
TI  - Negative Prospective Memory in Alzheimer's Disease: "Do Not Perform That Action".
AB  - Relatively to "standard" prospective memory, i.e., remembering to perform a
      future action, little is known about negative prospective memory, i.e.,
      remembering not to perform a future action. This study investigated the latter
      ability in Alzheimer's disease (AD). AD participants and healthy older adults
      were asked to click on the keyboard or not to click on it when a cue word was
      encountered. Results showed more omissions (i.e., forgetting to click the
      keyboard when the instruction was to do so) in AD participants than in healthy
      older adults, suggesting a prospective memory deficit. Interestingly, more
      commissions (i.e., clicking the keyboard when the instruction was not to do so)
      were also observed in AD participants than in healthy older adults. Similar
      levels of commissions and omissions were observed in AD participants and in
      healthy older adults. Also, commissions and omissions were correlated with
      performance on an inhibition assessment task. Our findings reveal that AD is
      characterized by not only difficulty in the retrieval of recent information, but
      also difficulty to inhibit no-longer appropriate stimulus-response associations
      previously learned, suggesting a specific deficit of negative prospective memory
      in AD.

PMID- 29226879
TI  - Diastasis recti associated with midline hernias: Totally subcutaneous video
      endoscopic repair.
AB  - A 63-year-old man with a history of a conventional cholecystectomy was referred
      to our department for an incisional subcostal hernia and chronic back pain.
      Physical examination also showed an umbilical hernia and diastasis recti
      measuring 6 cm that was confirmed with a computed tomography scan. Subcutaneous
      video-endoscopic repair was done repairing all defects simultaneously.

PMID- 29226880
TI  - Sewing machine technique for laparoscopic mesh fixation in intra-peritoneal on
      lay mesh.
AB  - Introduction: : Mesh fixation in laparoscopic ventral hernia is accomplished
      using tacks or tacks with transfascial sutures. This is a painful operation and
      the pain is believed to be more due to transfascial sutures. We describe a method
      of transfascial suturing which fixes the mesh securely and probably causes less
      pain. Method: : Up to six ports may be necessary, three on each side. A suitable
      sized mesh is used and fixed with tacks all around. A 20G spinal needle is passed
      from the skin through one corner of the mesh. A 0 prolene suture is passed
      through into the peritoneum. With the prolene within, the needle is withdrawn
      above the anterior rectus sheath and passed again at an angle into the abdomen
      just outside the mesh. A loop of prolene is thus created which is tied under
      vision using intra-corporeal knotting. Conclusion: : This method gives a secure
      mesh fixation and causes less pain than conventional methods. This technique is
      easy to learn but needs expertise in intra-corporeal knotting.

PMID- 29226881
TI  - Surgical outcome of laparoscopic hepatic resection for hepatocellular carcinoma:
      A matched case-control study with propensity score matching.
AB  - Background: Although the number of reports on laparoscopic hepatic resection
      (LHR) has increased, studies of long-term outcomes regarding tumor recurrence and
      patient survival compared to the conventional open approach are limited. We
      evaluated the long-term survival and feasibility of LHR in patients with
      hepatocellular carcinoma (HCC). Patients and Methods: A retrospective analysis
      was performed on the clinical data of patients who underwent hepatic resection
      for primary HCC between August 2000 and December 2013. The patients were divided
      into the LHR or open hepatic resection (OHR) groups. To control for selection
      bias in the two groups, propensity score matching was used at a 1:1 ratio based
      on the following covariates: Child-Pugh grade, tumour size, tumour number and
      tumour location. Following propensity score matching, thirty patients were
      included in the LHR group and thirty were included in the OHR group. Results: The
      respective disease-free survival rates at 1 year, 3 years and 5 years were 78.4%,
      61.1% and 38.9%, respectively, for the LHR group, and 89.3%, 57.5% and 47.9%,
      respectively, for the OHR group (P = 0.89). Also, the overall survival rates at 1
      year, 3 years and 5 years were 96.4%, 68.2% and 62.5%, respectively, for the LHR
      group and 100.0%, 95.8% and 72.3%, respectively, for the OHR group (P = 0.44).
      Conclusions: According to our study, using propensity score matching, LHR for HCC
      is safe, feasible and comparative, with good oncologic results.

PMID- 29226882
TI  - Concomitant intraperitoneal onlay mesh repair with endoscopic component
      separation and sleeve gastrectomy.
AB  - Bariatric surgery can be safely combined with laparoscopic intraperitoneal onlay
      mesh (IPOM) repair. In case of large ventral hernias, laparoendoscopic component
      separation can also be combined to achieve tension-free closure of the defect.
      Concomitant bariatric surgery and hernia repair also offer the additional benefit
      of reduction in recurrence of hernias as obesity, one of the risk factors, is
      treated in the process. We present a case of 60-year-old man with a body mass
      index of 45.3 kg/m2 with a large recurrent ventral hernia. We performed a lap
      sleeve gastrectomy with laparoendoscopic anterior component separation with IPOM.
      The operative steps included hernia contents reduction, conventional sleeve
      gastrectomy, anterior component separation on either side, intra-corporeal
      closure of hernia defect and placement of a composite mesh. Patient recovery was
      uneventful. Concomitant bariatric surgery with laparoendoscopic component
      separation with IPOM may be safe, but more studies are required.

PMID- 29226883
TI  - Deep vein thrombosis prophylaxis: Are we overdoing? An Asian survey on trends in
      bariatric surgery with a systematic review of literature.
AB  - Background: Obesity is a risk factor for deep vein thrombosis (DVT) and venous
      thromboembolism (VTE). VTE is the most common cause of mortality in patients
      undergoing bariatric surgery. There is considerable variation in practice
      regarding methods, dosages and duration of prophylaxis in this patient
      population. Most of the literature is based on Western patients and specific
      guidelines for Asians do not exist. Methods: We conducted a web-based survey
      amongst 11 surgeons from high-volume centres in Asia regarding their DVT
      prophylaxis measures in patients undergoing bariatric surgery. We collected and
      analysed the data. Results: The reported incidence of DVT and VTE ranged from 0%
      to 0.2%. Most surgeons (63.64%) preferred to use both mechanical and
      chemoprophylaxis with low-molecular-weight heparin being the most preferred form
      of chemoprophylaxis (81.82%). There was an equal distribution of weight-based,
      body mass index-based and fixed-dose regimens. Duration of chemoprophylaxis
      ranged from 3-5 days after surgery to 2 weeks after surgery. For high-risk
      patients, 60% surgeons preferred to start chemoprophylaxis at least 1 week before
      surgery. Routine use of inferior vena cava filters in high-risk patients was not
      preferred with some surgeons adopting a selective use (36.36%). Conclusion: The
      purpose of this survey was to understand the trends in DVT prophylaxis amongst
      different high-volume bariatric centres in Asia and to relate the same with the
      existing literature on the different steps in prophylaxis. There is, however, a
      need for consensus guidelines for DVT prophylaxis in Asian obese.

PMID- 29226884
TI  - Application of fluorescent cholangiography during single-incision laparoscopic
      cholecystectomy for cholecystitis with a right-sided round ligament: Preliminary
      experience.
AB  - An 82-year-old woman was diagnosed with cholecystitis with a right-sided round
      ligament. We planned a single-incision laparoscopic cholecystectomy. Based on the
      findings of fluorescent cholangiography, the running course of the common bile
      duct was confirmed before dissection of Calot's triangle, and the confluence
      between the cystic duct and the common bile duct was exposed after the dissection
      of Calot's triangle. The planned surgery was successful. The operative time and
      intraoperative blood loss were 157 min and 2 mL, respectively. The patient was
      discharged from our hospital 3 days after surgery. Application of fluorescent
      cholangiography during a laparoscopic cholecystectomy for the patients with a
      right-sided round ligament should be widely accepted.

PMID- 29226885
TI  - Peritoneal pocket hernia: A distinct cause of early postoperative small bowel
      obstruction and strangulation: A report of two cases following robotic
      herniorrhaphy.
AB  - Laparoscopic and robotic hernia surgery offers advantages over open herniorrhaphy
      including faster recover and lower wound infection but is associated with rare
      but serious complications such as visceral injury and intestinal obstruction. We
      describe two cases of small bowel obstruction with strangulation that occurred
      shortly after routine robotic hernia surgery. We define this rare type of
      strangulating internal hernia as a peritoneal pocket hernia and call attention to
      its diagnosis and management.

PMID- 29226886
TI  - Two cases of laparoscopic direct spiral closure of large defects in the second
      portion of the duodenum after laparoscopic endoscopic co-operative surgery.
AB  - Curative endoscopic resection of non-ampullary duodenal lesions, although
      possible, is challenging. In recent years, although a novel surgical technique
      named laparoscopic-endoscopic cooperative surgery (LECS), which combines
      laparoscopic and endoscopic techniques, has made the resection of nonampullary
      duodenal lesions relatively easier, closure of the defect is still controversial.
      We report two cases of the duodenal lesion which were closed using a novel
      technique for primary closure utilising the free wall of the duodenum. Two cases
      of the duodenal lesion in the second portion of the duodenum were undergone full
      thickness resection using the LECS technique. The defect is designed spirally to
      ensure maximum use of the free wall of the duodenum. The mucosal layer is closed
      using a running suture, and the seromuscular layer is closed using interrupted
      sutures. The suture line is then reinforced with omentum. There were no
      intraoperative complications and had uneventful post-operative courses with no
      leakage, stenosis, or relapse.

PMID- 29226887
TI  - [Updates in 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral
      Arterial Diseases].

PMID- 29226888
TI  - [Bicuspid aortic valve, valve phenotypes and relation with complications].

PMID- 29226889
TI  - Assessment of bicuspid aortic valve phenotypes and associated pathologies: A
      transesophageal echocardiographic study.
AB  - OBJECTIVE: We investigated the frequency of different bicuspid aortic valve
      disease (BAV) phenotypes,the associated valvular pathologies, and the aortopathy
      phenotypes, using 2-dimensional (2D) transthoracic, 2D transesophageal
      echocardiography (TEE) and 3-dimensional (3D) TEE. METHODS: A total of 154
      patients with BAV were included. Five BAV phenotypes were detected. To better
      define valvular pathologies, binary classifications of BAV were used: BAV with
      antero-posterior commisural line (BAV-AP) and right-left commissural line (BAV
      RL). Aortopathy phenotype was classified according to the involved tract(s).
      RESULTS: Of the patients, 53.2% had type 1, 16.2% type 2, 15.6% type 3, 1.3% type
      4, and 13.6% had type 5 BAV. The prevalence of BAV-AP and BAV-RL was 68.2% and
      31.8%, respectively. No difference was detected with respect to aortic
      regurgitation between BAV-AP and BAV-RL (p=0.9), but the BAVRL group had an
      increased propensity to have a stenotic aortic valve (p=0.003). The indexed
      aortic diameter was larger in BAV-AP cases than BAV-RL at the sinus of Valsalva
      (p=0.008). In patients with dilatation of the root and tubular portion, a
      predominance of BAV-AP versus BAV-RL was observed (85% vs 15%). A markedly low
      prevalence of the root phenotype (3.2%) was observed. In 90.1% of the patients,
      2D TEE was sufficient to classify BAV phenotypes; further 3D imaging was needed
      in 9.9% of the cases. CONCLUSION: There may be racial differences in the
      frequency of valvular and aortopathy phenotypes in patients with BAV. BAV
      phenotypes differ with respect to aortic stenosis and aortopathy phenotypes. TEE
      may have good diagnostic utility in differentiating BAV phenotypes.

PMID- 29226890
TI  - Relationship between the extent of coronary artery disease and in-stent
      restenosis in patients with acute ST-segment elevation myocardial infarction
      undergoing primary percutaneous coronary intervention.
AB  - OBJECTIVE: The pathophysiological mechanism of in-stent restenosis (ISR) is
      different from atherosclerosis of native coronary arteries. The aim of this study
      was to evaluate the relationship between ISR and the extent of coronary artery
      disease (CAD), and to identify other risk factors associated with ISR in ST
      segment elevation myocardial infarction (STEMI) patients. METHODS: A total of 372
      consecutive patients presenting with first acute STEMI who were successfully
      treated with primary percutaneous coronary intervention within 12 hours from the
      onset of symptoms and who had an angiographic follow-up at 3 months were included
      in the study. The extent of CAD was calculated using the Gensini score. RESULTS:
      The incidence of ISR observed in our group of patients was 23.4% (n=87). The mean
      Gensini score was significantly higher in patients with ISR when compared with
      group without restenosis (69 [range: 51-90] vs 42 [range: 32-61]; p<0.001). The
      presence of diabetes mellitus, left ventricular ejection fraction (LVEF), and low
      density lipoprotein cholesterol (LDL-C) level differed significantly between the
      2 groups (p<0.05 for all). Stent diameter and stent length were found to be
      significantly different between the ISR group and the no-restenosis group (p<0.05
      for both). In multivariate logistic regression analysis, the Gensini score, stent
      diameter, stent length, LVEF, and LDLC were independently associated with ISR.
      CONCLUSION: Despite the differences in the underlying pathophysiological
      mechanism of ISR and native coronary atherosclerosis, patients with a greater
      extent of CAD should be considered candidates for future stent restenosis.

PMID- 29226891
TI  - The relationship between right ventricular outflow tract fractional shortening
      and Pulmonary Embolism Severity Index in acute pulmonary embolism.
AB  - OBJECTIVE: Right ventricular (RV) functions are clinically important in acute
      pulmonary embolism (APE). Measurement of systolic function of the right
      ventricular outflow tract (RVOT) with echocardiography is a simple method to
      evaluate RV function. The aim of this study was to determine the relationship
      between RVOT systolic function and the Pulmonary Embolism Severity Index (PESI).
      METHODS: A total of 151 patients diagnosed with APE by pulmonary computed
      tomography angiography or ventilation/perfusion scintigraphy were included.
      Patients were assigned to 2 groups based on the simplified PESI (sPESI): sPESI <1
      (n=85) and sPESI >=1 (n=66). RV conventional parameters, RVOT dimensions, and
      fractional shortening (RVOT-FS) were also measured. RESULTS: Mean age was similar
      between sPESI <1 and >1 patients (58.7+/-12.9 years vs. 61.1+/-12.7 years,
      respectively). Frequency of male gender was significantly higher in PESI <1 group
      (61.2% vs. 40.2%, p=0.013). No significant differences were found between the
      groups in fasting glucose, serum creatinine, hemoglobin, C-reactive protein,
      erythrocyte sedimentation rate, troponin, and D-dimer levels, and left
      ventricular ejection fraction. RVOT-FS was higher in patients with sPESI <1 than
      in patients with sPESI >=1 (34.41+/-3.56 vs. 22.98+/-4.22), and this difference
      was significant (p<0.001). Tricuspid annular plane systolic excursion values were
      lower and pulmonary artery systolic pressure values were higher in the sPESI >=1
      group, which was also statistically significant (p<0.05). Mortality occurred in 7
      patients with sPESI <1 and in 16 patients with sPESI >=1. The mortality rate was
      higher in patients with lower RVOT-FS, and a RVOT-FS <0.22 predicted mortality
      with a sensitivity of 54.5% (AUC: 0.674, 95% CI 0.552-0.796; p=0.009).
      CONCLUSION: The RVOT-FS is a noninvasive measurement of RV systolic function, is
      well-correlated with the sPESI score, and associated with mortality in patients
      with APE. This easily applied measurement may be used to predict short-term
      mortality in patients with APE.

PMID- 29226892
TI  - Evaluation of increase in intraventricular gradient and dynamic obstruction
      during exercise stress test in competitive runners.
AB  - OBJECTIVE: Sudden cardiac death in athletes is one of the most tragic health
      events seen both in our country and all over the world. In some of those
      athletes, there is no obvious structural abnormality. Dynamic changes in
      intracardiac hemodynamics during exercise may be a cause for sudden death in
      these athletes, the impact of exercise on intracardiac gradient and cardiac
      hemodynamic parameters in athletes was compared with healthy controls. METHODS: A
      total of 21 professional male athletes and 21 healthy male controls were included
      in the study. Transthoracic echocardiography was performed in all participants
      both at rest and maximal exercise level to assess the intraventricular gradient
      (IVG) and cardiac systolic and diastolic functions. Abnormal IVG was defined as
      gradient of >30 mm Hg at peak exercise level. RESULTS: Both groups reached the
      level of predicted maximum exercise. There was no exercise limiting symptom among
      participants during exercise test. The athletes revealed a higher maximum peak
      systolic IVG at baseline and after exercise in comparison with the control group.
      None of the participants showed an abnormal IVG level. CONCLUSION: Our results
      showed that there was no dynamic intraventricular obstruction with aerobic
      exercise in subjects with a structurally normal heart.

PMID- 29226893
TI  - Assessment of factors related to statin non-adherence in patients with
      established coronary artery disease: A single-center observational study.
AB  - OBJECTIVE: Lifelong statin treatment is recommended in patients with
      cardiovascular diseases, but drug adherence is a significant problem. The aim of
      this study was to investigate factors related to statin discontinuation in high
      risk patients with coronary artery disease (CAD) diagnosed by coronary
      angiography. METHODS: A total of 300 consecutive patients who were followed-up
      with a diagnosis of CAD were recruited. Patients were categorized as statin
      adherent or statin non-adherent (patients interrupting statin therapy >30 days).
      Study participants completed a questionnaire regarding demographic
      characteristics, medical history, knowledge of statin treatment, and factors
      related to statin discontinuation. RESULTS: In all, 160 patients (53.3%) were
      found to be statin adherent. Of those, 122 patients had suffered myocardial
      infarction, and atorvastatin was the most prescribed statin on discharge. Among
      the study population, 26% were illiterate and 55% had graduated from primary
      school. Only 39 cases (13%) cases had a low-density lipoprotein-cholesterol level
      <70 mg/dL. In 60% of the statin non-adherent patients, the reason for statin
      discontinuation was physician discontinuation of the statin prescription. In 14%,
      the patient stopped the therapy after cholesterol parameters had been reduced or
      reached the normal range. Only 8% of participants reported that negative
      information received from TV programs and social media was responsible for the
      decision to terminate drug use. CONCLUSION: Our findings demonstrated that the
      importance of intensive statin treatment in CAD patients has not been recognized
      by patients or many physicians. Adherence to statin treatment and success of the
      therapy is low, leading to unnecessarily high cholesterol levels in patients with
      CAD.

PMID- 29226894
TI  - Identifying undiagnosed or undertreated patients with familial
      hypercholesterolemia from the laboratory records of a tertiary medical center.
AB  - OBJECTIVE: Familial hypercholesterolemia (FH) is a life-threatening genetic
      disease associated with elevated low-density lipoprotein cholesterol (LDL-C) and
      premature coronary heart disease that is undiagnosed and undertreated around the
      world. This study aimed to examine the demographic characteristics, awareness,
      and treatment adherence of undiagnosed or undertreated FH patients based on
      laboratory records. METHODS: In a 16-month retrospective survey using laboratory
      records, patients with elevated LDL-C (>250 mg/dL) were identified (n=395).
      Patients younger than 18 years of age or with secondary causes of dyslipidemia
      were excluded (n=98). In all, 297 patients were called and asked to participate
      in a phone interview regarding their demographic characteristics, awareness of
      dyslipidemia, and treatment adherence. RESULTS: A total of 147 patients (mean
      age: 51.7+/-16.6 years; 59.2% female) completed the interview. The mean LDL-C
      level of the patients was 292.8+/-49.9 mg/dL. According to the Dutch Lipid Clinic
      Network criteria, 18.4% of the patients had definite FH, 66.0% had probable FH,
      and 15.6% had possible FH. Although the majority of the patients (93.9%) were
      aware of their high LDL-C level, only about half of them (n=75; 51.0%) were in
      treatment. Of all the patients who were interviewed, 21% (n=31) had never taken
      medication to lower their LDL-C, and 28% (n=41) had stopped taking a lipid
      lowering drug. CONCLUSION: This pilot study revealed that a significant number of
      FH patients were not taking statins despite having a very high LDL-C level.
      Nationwide detection of likely FH patients using hospital records and
      interviewing them via a phone survey may help to better understand and manage
      these high-risk patients.

PMID- 29226895
TI  - A late complication of coronary artery perforation during primary percutaneous
      coronary intervention: Coronary arteriovenous fistula.
AB  - Coronary artery perforation (CAP) is a rare, but potentially mortal possible
      complication of percutaneous coronary intervention. There are several treatment
      options for this complication, including prolonged balloon dilatation, use of a
      coronary stent graft, and bypass surgery. In this case report, a 65-year-old
      female patient who was admitted to the catheter laboratory with a diagnosis of
      acute coronary syndrome, was presented. Coronary angiography revealed total
      occlusion in the mid segment of the right coronary artery and a drug-eluting
      stent was implanted under 12 atm of pressure following pre-dilatation with a
      perfusion balloon. In order to perform defragmentation of the thrombus shifted
      into the proximal stent segment, post-dilatation was performed with a stent
      balloon (4-6 atm). After post-dilatation, an Ellis Class II perforation
      developed. In order to control the bleeding, a coronary stent graft was implanted
      at the perforation area. The rupture was sealed. Control coronary angiography 40
      days later indicated that the stent graft was patent, but an arteriovenous
      fistula (AVF) draining to the right ventricle was detected. To the best of our
      knowledge, this is the first case of AVF seen as a late complication of CAP
      treated with a stent graft.

PMID- 29226896
TI  - Recovery of cardiomyopathy induced by ventricular premature beats of paraHisian
      origin after successful radiofrequency catheter ablation.
AB  - A 51-year-old male patient presented with frequent and symptomatic premature
      ventricular complexes (PVCs) that had induced cardiomyopathy. Radiofrequency (RF)
      catheter ablation of the origin of the PVCs was planned and the patient underwent
      electrophysiological study. During activation mapping, the earliest ventricular
      activation was identified at the His bundle region. Small His bundle electrogram
      recording by the distal ablation electrode during sinus rhythm revealed that the
      earliest ventricular activation during PVC preceded the QRS onset by 58
      milliseconds. The PVCs were successfully eliminated without occurrence of
      atrioventricular block using incremental application of RF energy to the para
      Hisian region. At the conclusion of a 5-month follow-up period, the patient
      remained asymptomatic and transthoracic echocardiography demonstrated an
      improvement in left ventricular ejection fraction.

PMID- 29226897
TI  - Treatment of ineffective endocardial defibrillation with subcutaneous array: a
      case report.
AB  - Defibrillation threshold (DFT) testing is an important part of ICD implantation.
      After placement of the ICD generator, a DFT test is performed to evaluate the
      integrity of the ICD system and to confirm a successful defibrillation safety
      margin. More than 6% of ICDs implanted are not within the DFT safety margin.
      Presently described is the case of a patient with a high DFT and some of the
      methods that can be used to manage this circumstance, including the use of a
      subcutaneous array.

PMID- 29226898
TI  - Severe cardiac toxicity following alcohol intake in a patient using therapeutic
      dose of propafenone.
AB  - An unconscious, 25-year-old, male patient was brought to the emergency
      department. The patient's electrocardiography demonstrated a wide QRS interval
      and first-degree atrioventricular block. He was being treated with propafenone
      twice daily (450 mg) for paroxysmal atrial fibrillation. The patient had consumed
      a substantial amount of alcohol the day before. He recovered after supportive
      management with sodium bicarbonate and inotropic therapy. In the presently
      described case, treatment resulted in quick normalization of QRS interval and
      stabilization of hemodynamic status.

PMID- 29226899
TI  - Successful resection and reconstruction of primary cardiac lymphoma.
AB  - Primary cardiac lymphoma (PCL) is one of the rarest tumors of the heart. The most
      common type is diffuse, large B-cell lymphoma. Most often, the right atrium and
      the right ventricle are involved, and if not diagnosed and treated in time, it
      can be fatal. In this case, a female patient underwent an urgent operation for a
      large, infiltrative, right atrial mass. Extensive resection of the lateral walls
      of both atria and the interatrial septum as well as reconstruction were performed
      successfully. The pathological evaluation suggested PCL. The aim of this case is
      to raise awareness of this disease and to highlight clinical and surgical
      approaches.

PMID- 29226900
TI  - Diffuse hypoplasia of the aortic arch and isthmus in a patient with Williams
      syndrome.
AB  - Williams syndrome is a rare neurodevelopmental disorder characterized by mental
      retardation, growth deficiency, hypercalcemia, cardiac defects, and a distinctive
      facial appearance. Cardiovascular abnormalities are present in approximately 80%
      of Williams syndrome patients. Surgical treatment is generally performed for
      supravalvular aortic stenosis, aortic coarctation, pulmonary artery stenosis, or
      ventricular septal defect. In rare cases, diffuse hypoplasia of the aortic arch
      with a normal left ventricular outflow tract and ascending aorta may be diagnosed
      in early childhood. Described herein is the case of a 16-month-old female with
      Williams syndrome and diffuse hypoplasia of the aortic arch and isthmus, and
      concomitant pulmonary stenosis and a ventricular septal defect. The patient
      underwent a successful surgical repair of the aortic arch with a modified
      pericardial patch technique.

PMID- 29226901
TI  - [How to evaluate hepatic vein flow using transthoracic echocardiography?]

PMID- 29226902
TI  - Case Image: Hiatal hernia presenting like a large left atrial mass.

PMID- 29226903
TI  - Case Image: Unruptured non-coronary sinus of Valsalva aneurysm presenting with
      nausea secondary to functional tricuspid stenosis.

PMID- 29226904
TI  - Interventricular septal lipoma.

PMID- 29226905
TI  - Case Image: Rare cause of recurrent pericardial tamponade: Cardiac angiosarcoma.

PMID- 29226906
TI  - Electrolyte Imbalances as a predisposing factor for arrhythmias.

PMID- 29226907
TI  - Authors' reply.

PMID- 29226908
TI  - New shock reduction programming strategies: Where do we stand?

PMID- 29226912
TI  - Innate immunity: Platelets on the prowl.

PMID- 29226911
TI  - Immunometabolism in 2017: Driving immunity: all roads lead to metabolism.

PMID- 29226910
TI  - Towards personalized, tumour-specific, therapeutic vaccines for cancer.
AB  - Cancer vaccines, which are designed to amplify tumour-specific T cell responses
      through active immunization, have long been envisioned as a key tool of effective
      cancer immunotherapy. Despite a clear rationale for such vaccines, extensive past
      efforts were unsuccessful in mediating clinically relevant antitumour activity in
      humans. Recently, however, next-generation sequencing and novel bioinformatics
      tools have enabled the systematic discovery of tumour neoantigens, which are
      highly desirable immunogens because they arise from somatic mutations of the
      tumour and are therefore tumour specific. As a result of the diversity of tumour
      neoepitopes between individuals, the development of personalized cancer vaccines
      is warranted. Here, we review the emerging field of personalized cancer
      vaccination and discuss recent developments and future directions for this
      promising treatment strategy.

PMID- 29226913
TI  - Correction to: Antiobesity potential of Piperonal: promising modulation of body
      composition, lipid profiles and obesogenic marker expression in HFD-induced obese
      rats.
AB  - [This corrects the article DOI: 10.1186/s12986-017-0228-9.].

PMID- 29226914
TI  - Longitudinal deformation bench testing using a coronary artery model: a new
      standard?
AB  - Objectives: To compare susceptibility of five different stent platforms with
      longitudinal stent deformation (LSD) using a clinically relevant bench testing
      model simulating both short and long malapposed lengths. Background: Recent data
      suggest that design modifications to the Promus Element stent which led to the
      Promus Premier stent has reduced susceptibility to LSD. However, susceptibility
      to LSD at long malapposed lengths has not been tested. Furthermore, the
      mechanisms behind susceptibility to LSD are as yet unclear. Methods: The Omega,
      Integrity, Multilink 8, Biomatrixand Promus Premier stent platforms were tested.
      The Omega, Integrity and Multilink 8 platforms were used in place of their drug
      eluting equivalents. 3.5 mm stents were deployed in a stepped tube with the
      distal portion fixed and the proximal test section exposed. The force required to
      compress stents by a fixed distance at different exposed lengths was compared.
      Symmetrical and point loading were used. Results: The Promus Premier was
      longitudinally as strong as Multilink and Integrity at a short exposed length (4
      mm) but weaker, in between Omega and the other platforms, at longer exposed
      lengths (12 mm). As previously noted, the Omega (Promus Element) platform was
      significantly weaker than the other stents and Biomatrix was the strongest stent.
      Conclusion: Susceptibility to LSD varies depending on length of malapposed
      segment when tested using a clinically relevant model as in this study. The
      mechanisms behind the susceptibility are likely multifactorial, including
      connector number, strut thickness, connector alignment and ring orientation but
      remain to be elucidated.

PMID- 29226915
TI  - Erratum: Factors that affect the onset of action of non-depolarizing
      neuromuscular blocking agents.
AB  - [This corrects the article on p. 500 in vol. 70, PMID: 29046769.].

PMID- 29226916
TI  - FDT 2.0: Improving scalability of the fuzzy decision tree induction tool -
      integrating database storage.
AB  - Effective machine-learning handles large datasets efficiently. One key feature of
      handling large data is the use of databases such as MySQL. The freeware fuzzy
      decision tree induction tool, FDT, is a scalable supervised-classification
      software tool implementing fuzzy decision trees. It is based on an optimized
      fuzzy ID3 (FID3) algorithm. FDT 2.0 improves upon FDT 1.0 by bridging the gap
      between data science and data engineering: it combines a robust decisioning tool
      with data retention for future decisions, so that the tool does not need to be
      recalibrated from scratch every time a new decision is required. In this paper we
      briefly review the analytical capabilities of the freeware FDT tool and its major
      features and functionalities; examples of large biological datasets from HIV,
      microRNAs and sRNAs are included. This work shows how to integrate fuzzy decision
      algorithms with modern database technology. In addition, we show that integrating
      the fuzzy decision tree induction tool with database storage allows for optimal
      user satisfaction in today's Data Analytics world.

PMID- 29226918
TI  - Bodily Extensions and Performance.

PMID- 29226917
TI  - Toward research-tested mobile health interventions to prevent diabetes and
      cardiovascular disease among persons with pre-diabetes.
AB  - Background: About 35% of US adults have pre-diabetes and an increased risk of
      diabetes. Consumer-facing devices such as the Fitbit help users become more
      physically active and manage their weight which reduces risk of diabetes and
      cardiovascular disease. Methods: In this commentary we provide a summary of
      healthy lifestyle intervention studies involving persons with pre-diabetes
      including those conducted in routine clinical practice. We also provide an
      account of how such interventions might be enhanced through the use of wearable
      devices linked to smartphone applications. Results: In initial trials focusing on
      overweight and obesity, consumer wearable devices have been shown to increase
      physical activity and reduce weight. However, the acceptability and effectiveness
      of these mHealth interventions among persons with impaired glucose tolerance or
      impaired fasting glucose is unknown; studies involving persons with pre-diabetes
      have not yet been reported. Conclusions: Research is needed to determine the
      feasibility and efficacy of wearable devices in improving physical activity and
      weight management in persons with pre-diabetes who are at-risk of diabetes and
      cardiovascular disease.

PMID- 29226919
TI  - Indispensable benefit of independent investigator-driven research in a changing
      clinical trial landscape.

PMID- 29226920
TI  - CoO microspheres and metallic Co evolved from hexagonal alpha-Co(OH)2 plates in a
      hydrothermal process for lithium storage and magnetic applications.
AB  - CoO microspheres and metallic Co could be successfully synthesized by simply
      reacting cobalt acetate with a mixture solvent of ethylene glycol and deionized
      water in a hydrothermal process for different times. As the reaction proceeded,
      alpha-Co(OH)2, CoO and metallic Co were produced. To understand the phase
      evolution processes from alpha-Co(OH)2 to CoO and then metallic Co, a range of
      time-dependent experiments were carried out, and the intermediate products
      obtained at different reaction times were investigated in detail. The
      investigation revealed that CoO microspheres were actually evolved from alpha
      Co(OH)2 as a precursor. Just elongating the reaction time, CoO microspheres could
      be further reduced to metallic Co. With a pure ethylene glycol medium for the
      same reaction, only alpha-Co(OH)2 could be generated, indicating an important
      role of water. When the obtained CoO microspheres were used as anode materials
      for lithium-ion batteries, they delivered a specific capacity of 803 mA h g-1 at
      0.1 A g-1 with a retention of 453 mA h g-1 after 70 cycles. Meanwhile, the
      magnetic properties of the obtained CoO microspheres and metallic Co were
      investigated, with the CoO microspheres showing an antiferromagnetic behavior and
      the metallic Co exhibiting ferromagnetic characteristics. This study suggested a
      novel method for synthesizing CoO with a uniform microsphere morphology and bulk
      metallic Co easily.

PMID- 29226921
TI  - Solution and gas phase evidence of anion binding through the secondary bonding
      interactions of a bidentate bis-antimony(iii) anion receptor.
AB  - The solution and gas phase halide binding to a bis-antimony(iii) anion receptor
      was studied. This new class of anion receptors utilizes the strong Sb-centered
      secondary bonding interactions (SBIs) that are formed opposite to the polar Sb-O
      primary bond. 1H NMR titration data were fitted statistically to binding models
      and solution-phase binding energetics were extracted, while the formation of
      anion-to-receptor complexes was observed using ESI-MS. Density functional theory
      calculations suggest that their affinity towards binding halide anions is
      mitigated by the strong explicit solvation effect in DMSO, which gives insights
      into future designs that circumvent direct solvent binding and are anticipated to
      yield tighter and perhaps more selectivity in anion binding.

PMID- 29226922
TI  - A polymyxin B-silver nanoparticle colloidal system and the application of
      lipopolysaccharide analysis.
AB  - Polymyxin B (PMB) is a small cyclic polycationic lipopeptide, which can be used
      as an antibiotic drug against Gram-negative bacteria. In this work, the
      interaction between citrate capped silver nanoparticles (AgNPs) and PMB is
      studied. Experimental results show that the association constant is extremely
      high and the binding event leads to a significant variation in the localized
      surface plasmon resonance (LSPR) of AgNPs. Moreover, the PMB-AgNP colloidal
      system can be further exploited as a sensitive analytical platform. Taking
      lipopolysaccharide (LPS) as an example, we demonstrate a facile colorimetric LPS
      detection method. LPS is a major constituent of the Gram-negative bacterial cell
      wall which is used as an optimal biomarker for some diseases like urinary tract
      infections and sepsis. In this study, target LPS is able to tightly bind to PMB,
      which effectively inhibits the PMB induced aggregation of AgNPs. By monitoring
      the UV-vis absorption spectra, the LPS concentration can be quantitatively
      determined with high sensitivity. The sensing strategy is quite simple, which
      allows effortless diagnosis of many diseases at different stages.

PMID- 29226923
TI  - Conformational control of nonplanar free base porphyrins: towards bifunctional
      catalysts of tunable basicity.
AB  - For the first time, free base and N-methylated porphyrins have been utilized as
      bifunctional organocatalysts in Michael additions and it was found that
      distortion of the macrocycle is a vital prerequisite for their catalytic
      activity. Conformational design has been used to tailor the properties of
      nonplanar porphyrins with regards to availability of the N-H units for hydrogen
      bonding (distortion-dependent hydrogen bonding) and the basicity of the
      heterocyclic groups. NMR spectroscopic- and catalyst screening studies provided
      insight into the likely mode of catalyst action. This unprecedented use of free
      base and N-substituted porphyrins as organocatalysts opens a new functional role
      for porphyrins.

PMID- 29226924
TI  - Analysis of the conformational properties of amine ligands at the gold/water
      interface with QM, MM and QM/MM simulations.
AB  - We describe a strategy of integrating quantum mechanical (QM), hybrid quantum
      mechanical/molecular mechanical (QM/MM) and MM simulations to analyze the
      physical properties of a solid/water interface. This protocol involves using a
      correlated ab initio (CCSD(T)) method to first calibrate Density Functional
      Theory (DFT) as the QM approach, which is then used in QM/MM simulations to
      compute relevant free energy quantities at the solid/water interface using a mean
      field approximation of Yang et al. that decouples QM and MM thermal fluctuations;
      gas-phase QM/MM and periodic DFT calculations are used to determine the proper QM
      size in the QM/MM simulations. Finally, the QM/MM free energy results are
      compared with those obtained from MM simulations to directly calibrate the force
      field model for the solid/water interface. This protocol is illustrated by
      examining the orientations of an alkyl amine ligand at the gold/water interface,
      since the ligand conformation is expected to impact the chemical properties
      (e.g., charge) of the solid surface. DFT/MM and MM simulations using the
      INTERFACE force field lead to consistent results, suggesting that the effective
      gold/ligand interactions can be adequately described by a van der Waals model,
      while electrostatic and induction effects are largely quenched by solvation. The
      observed differences among periodic DFT, QM/MM and MM simulations, nevertheless,
      suggest that explicitly including electronic polarization and potentially charge
      transfer in the MM model can be important to the quantitative accuracy. The
      strategy of integrating multiple computational methods to cross-validate each
      other for complex interfaces is applicable to many problems that involve both
      inorganic/metallic and organic/biomolecular components, such as functionalized
      nanoparticles.

PMID- 29226925
TI  - Novel double layer lanthanide metal-organic networks for sensing applications.
AB  - A trifunctional aromatic building block (H2L) containing three different types of
      functional groups (carboxyl C([double bond, length as m-dash]O)OH, aldehyde
      C([double bond, length as m-dash]O)H, and O-ether) was applied for the
      hydrothermal synthesis of two novel lanthanide 2D coordination polymers [Ln(MU
      HL)(MU3-L)(phen)]n {Ln = Tb (1) and Eu (2); H2L = 5-methoxy-(4-benzaldehyde)-1,3
      benzene dicarboxylic acid; phen = 1,10-phenanthroline}. Both compounds 1 and 2
      are isostructural and reveal very complicated 2D metal-organic double layers with
      the 3,4L27 topology. The presence of free aldehyde groups positioned outside of
      the double layers opens up a possibility of using them as functional groups
      toward sensing amines and small organic molecules. The fluorescence measurements
      for the Tb derivative 1 reveal that it acts as an efficient fluorescence sensor
      for p-phenylenediamine, benzidine and acetone molecules via a luminescence
      quenching effect. A similar sensing behavior was observed for the Eu compound 2.
      Moreover, thin-films of 1-PEG on glass (1-PEG-glass thin-film material) were
      fabricated and investigated for the detection of amine vapors.

PMID- 29226926
TI  - QSAR modeling of cumulative environmental end-points for the prioritization of
      hazardous chemicals.
AB  - The hazard of chemicals in the environment is inherently related to the molecular
      structure and derives simultaneously from various chemical
      properties/activities/reactivities. Models based on Quantitative Structure
      Activity Relationships (QSARs) are useful to screen, rank and prioritize
      chemicals that may have an adverse impact on humans and the environment. This
      paper reviews a selection of QSAR models (based on theoretical molecular
      descriptors) developed for cumulative multivariate endpoints, which were derived
      by mathematical combination of multiple effects and properties. The cumulative
      end-points provide an integrated holistic point of view to address
      environmentally relevant properties of chemicals.

PMID- 29226927
TI  - Tunable white-light emission by supramolecular self-sorting in highly swollen
      hydrogels.
AB  - Fluorescence-tunable hydrogels especially emitting white-light were achieved by
      swelling hydrogels in solutions containing two kinds of dyes. The fluorescence of
      the dyes was enhanced by the orthogonal supramolecular complexation with
      different binding sites in the hydrogels.

PMID- 29226928
TI  - Evaluation of the in vivo acute antiinflammatory response of curcumin-loaded
      nanoparticles.
AB  - Curcumin is the main curcuminoid found in turmeric rhizomes and is a strong
      candidate to formulate foodstuff with specific properties. Among various
      bioactive properties of curcumin, its antiinflammatory activity is remarkable; on
      the other hand, its low water solubility leads to low absorption. Thus, new
      formulations need to be developed to improve its efficacy, and encapsulation is a
      promising alternative strategy in this regard. The objective of the present study
      was to obtain curcumin-loaded polyvinylpyrrolidone (PVP) nanoparticles and
      evaluate their acute in vivo antiinflammatory activity. Nanoparticles were
      obtained by complexation using the solid dispersion technique, and the
      characterization of nanoparticles showed that curcumin and PVP formed an
      amorphous solid solution. Encapsulated curcumin was colloidally stable in
      distilled water; this was attributed to the formation of hydrogen bonds between
      curcumin hydroxyl and PVP carbonyl groups. Rats were treated orally with single
      doses of curcumin and curcumin-loaded PVP nanoparticles, and antiinflammatory
      activity was evaluated by an experimental model of carrageenan-induced paw edema,
      myeloperoxidase (MPO) activity, and microcirculation in situ. Treatment with
      nanoparticles at 12.5 mg kg-1 significantly reduced the intensity of edema and
      MPO activity, whereas pure curcumin only presented a significant effect at 400 mg
      kg-1. Curcumin inhibited cell migration since rolling and adherent leukocytes
      were significantly reduced using nanoparticles at 50 mg kg-1 and curcumin at 400
      mg kg-1. Compared to free curcumin, encapsulated curcumin was effective at lower
      doses; this might be due to the improved water affinity and colloidal stability
      of curcumin nanoparticles.

PMID- 29226929
TI  - Synergistic arsenic(v) and lead(ii) retention on synthetic jarosite. I.
      Simultaneous structural incorporation behaviour and mechanism.
AB  - Jarosite [KFe3(SO4)2(OH)6] minerals are effective scavengers of potentially toxic
      elements (PTEs) and are abundant, for example, in acid rock/mine drainage
      scenarios. The retention process is highly relevant for environmental attenuation
      of heavy metals and metalloids since these are usually highly soluble and thus
      mobile under acidic conditions. We investigated both macroscopically and at the
      molecular scale the extent and the effects of concomitant incorporation of As(v)
      and Pb(ii) into synthetic jarosite at different As/Pb starting molar ratios,
      using XRD-Rietveld, SEM, ATR-FTIR spectroscopy and wet chemistry. The amount of
      arsenate substituted in the jarosite structure was larger when Pb(ii) was also
      incorporated, the former filling up to approximately 33% of the tetrahedral sites
      normally occupied by SO42-, as compared to 21% when Pb(ii) was absent. Similarly,
      the amount of Pb(ii) incorporated in the structure was larger when As(v) was also
      taken up. The jarosite unit cell volume increased as higher amounts of As(v)
      incorporated into its structure, but simultaneous Pb(ii) incorporation seemed to
      limit this increase due to its smaller size as compared to K+. The extent to
      which As and Pb can accommodate in the jarosite structure was found to be limited
      by concentration maxima under the imposed synthesis conditions. At As/Pb ratios
      up to 1, Pb-As-jarosites were the only crystalline products. Above this ratio, a
      mixture of Pb-As-jarosite, anglesite (PbSO4) and poorly-crystalline ferric
      arsenate (AFA) phases was observed. At the highest As/Pb ratio investigated of
      1.80 Pb-As-jarosite was no longer formed. Infrared spectroscopy analysis was
      applied for the first time here to substituted jarosites with both cations and
      anions, showing spectral changes in the solids as the As/Pb ratio increased: a
      characteristic As-O doublet at ~810 and ~855 cm-1 was observed upon Pb
      incorporation, showing an indirect effect of Pb(ii) on the As-O bonds in the
      jarosite structure. Thus, structural incorporation of Pb plays a pivotal role in
      the unit cell environment of jarosite to balance the distortion caused by AsO4
      for-SO4 substitution. The retention processes found in this work have important
      environmental implications and impacts: through the synergistic incorporation
      encountered, remediation enhancement of cationic pollutants such as Pb(ii) is
      possible in a concomitant fashion with As(v) attenuation in acidic mining and
      metallurgical environments.

PMID- 29226930
TI  - Soft network materials with isotropic negative Poisson's ratios over large
      strains.
AB  - Auxetic materials with negative Poisson's ratios have important applications
      across a broad range of engineering areas, such as biomedical devices, aerospace
      engineering and automotive engineering. A variety of design strategies have been
      developed to achieve artificial auxetic materials with controllable responses in
      the Poisson's ratio. The development of designs that can offer isotropic negative
      Poisson's ratios over large strains can open up new opportunities in emerging
      biomedical applications, which, however, remains a challenge. Here, we introduce
      deterministic routes to soft architected materials that can be tailored precisely
      to yield the values of Poisson's ratio in the range from -1 to 1, in an isotropic
      manner, with a tunable strain range from 0% to ~90%. The designs rely on a
      network construction in a periodic lattice topology, which incorporates zigzag
      microstructures as building blocks to connect lattice nodes. Combined
      experimental and theoretical studies on broad classes of network topologies
      illustrate the wide-ranging utility of these concepts. Quantitative mechanics
      modeling under both infinitesimal and finite deformations allows the development
      of a rigorous design algorithm that determines the necessary network geometries
      to yield target Poisson ratios over desired strain ranges. Demonstrative examples
      in artificial skin with both the negative Poisson's ratio and the nonlinear
      stress-strain curve precisely matching those of the cat's skin and in unusual
      cylindrical structures with engineered Poisson effect and shape memory effect
      suggest potential applications of these network materials.

PMID- 29226931
TI  - Development of visible-light responsive and mechanically enhanced "smart" UCST
      interpenetrating network hydrogels.
AB  - An interpenetrating polymer network (IPN), chlorophyllin-incorporated
      environmentally responsive hydrogel was synthesized and exhibited the following
      features: enhanced mechanical properties, upper critical solution temperature
      (UCST) swelling behavior, and promising visible-light responsiveness. Poor
      mechanical properties are known challenges for hydrogel-based materials. By
      forming an interpenetrating network between polyacrylamide (PAAm) and
      poly(acrylic acid) (PAAc) polymer networks, the mechanical properties of the
      synthesized IPN hydrogels were significantly improved compared to hydrogels made
      of a single network of each polymer. The formation of the interpenetrating
      network was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), the
      analysis of glass transition temperature, and a unique UCST responsive swelling
      behavior, which is in contrast to the more prevalent lower critical solution
      temperature (LCST) behaviour of environmentally responsive hydrogels. The visible
      light responsiveness of the synthesized hydrogel also demonstrated a positive
      swelling behavior, and the effect of incorporating chlorophyllin as the
      chromophore unit was observed to reduce the average pore size and further enhance
      the mechanical properties of the hydrogel. This interpenetrating network system
      shows potential to serve as a new route in developing "smart" hydrogels using
      visible-light as a simple, inexpensive, and remotely controllable stimulus.

PMID- 29226932
TI  - Ligand-induced decarbonylation in diphosphine-ligated palladium acetates
      [CH3CO2Pd((PR2)2CH2)]+ (R = Me and Ph).
AB  - A new decarbonylation reaction is observed for [(K2-acetate)Pd(K2-diphosphine)]+
      complexes. Gas-phase IR experiments identify the product as
      [CH3Pd(OP(Ph2)CH2PPh2)]+. DFT calculations uncovered a plausible mechanism
      involving O atom abstraction by the diphosphine ligand within the coordination
      sphere to yield the acetyl complex, [CH3COPd(OP(Ph2)CH2PPh2)]+, which then
      undergoes decarbonylation.

PMID- 29226933
TI  - Highly efficient asymmetric construction of novel indolines and
      tetrahydroquinoline derivatives via aza-Barbier/C-N coupling reaction.
AB  - Highly stereoselective syntheses of chiral indolines and tetrahydroquinolines are
      achieved by combining the asymmetric Zn-mediated allylation of chiral N-tert
      butanesulfinyl imines with efficient intramolecular C-N cross-coupling. Herein,
      the advantages of such a synthetic strategy are illustrated by the synthesis of
      indolines and tetrahydroquinolines with quaternary stereocenters and multi
      substituted 1-oxo-1,2,3,4-tetrahydroisoquinolines.

PMID- 29226934
TI  - Improved synthesis of 8-oxabicyclo[3.2.1]octanes via tandem C-H oxidation/oxa
      [3,3] Cope rearrangement/aldol cyclization.
AB  - A tandem C-H oxidation/oxa-[3,3] Cope rearrangement/aldol reaction of allylic
      silylethers promoted by T+BF4-(tempo oxoammonium tetrafluoroborate)/ZnBr2 has
      been successfully developed allowing the efficient construction of 8
      oxabicyclo[3.2.1]octanes and their analogs with a wide substrate scope.

PMID- 29226935
TI  - Collective behavior of bulk nanobubbles produced by alternating polarity
      electrolysis.
AB  - Nanobubbles in liquids are mysterious gaseous objects with exceptional stability.
      They promise a wide range of applications, but their production is not well
      controlled and localized. Alternating polarity electrolysis of water is a tool
      that can control the production of bulk nanobubbles in space and time without
      generating larger bubbles. Using the schlieren technique, the detailed three
      dimensional structure of a dense cloud of nanobubbles above the electrodes is
      visualized. It is demonstrated that the thermal effects produce a different
      schlieren pattern and have different dynamics. A localized volume enriched with
      nanobubbles can be separated from the parent cloud and exists on its own. This
      volume demonstrates buoyancy, from which the concentration of nanobubbles is
      estimated as 2 * 1018 m-3. This concentration is smaller than that in the parent
      cloud. Dynamic light scattering shows that the average size of nanobubbles during
      the process is 60-80 nm. The bubbles are observed 15 minutes after switching off
      the electrical pulses but their size is shifted to larger values of about 250 nm.
      Thus, an efficient way to generate and control nanobubbles is proposed.

PMID- 29226936
TI  - Coordination chemistry of stannylene-based Lewis pairs - insertion into M-Cl and
      M-C bonds. From base stabilized stannylenes to bidentate ligands.
AB  - The coordination chemistry of intramolecular stannylene phosphorus Lewis pairs
      incorporated into four membered ring systems is presented. Previously reported
      coordination chemistry of stannylene and phosphorus towards palladium(0) is
      extended by using Pd(nbe)3 as a precursor, yielding co-ligand free complexes. An
      equilibrium of one or two stannylene phosphorus ligands coordinated to Pd(0) was
      observed with tin acting either as a donor or an acceptor towards palladium.
      Furthermore, the reactions with transition metal(i) chlorides, [(cod)IrCl]2,
      [(cod)RhCl]2 and Me2SAuCl are reported. They proceed via insertion of stannylene
      into the M-Cl bonds, yielding metal complexes with chelating stannide phosphorus
      ligands. For gold, a dinuclear complex with bridging P-Sn ligands was formed.
      Furthermore, the reaction of a P -> Sn Lewis pair in a three membered ring system
      with (cod)PtMe2 is reported.

PMID- 29226937
TI  - High-yield synthesis of a unique Mn(iii) siloxide complex through KMnO4 oxidation
      of a Mn(ii) precursor.
AB  - A unique trivalent manganese siloxide complex, blue-violet
      MnIIILi2Cl[(Ph2SiO)2O]2(THF)4.2THF (3) has been prepared by a straightforward two
      step synthetic protocol. Lithiation of (Ph2SiOH)2O (1) followed by reaction with
      MnCl2(THF)2 gave the structurally remarkable Mn(ii) precursor
      MnIILi4Cl2[(Ph2SiO)2O]2(THF)5.2THF (2). Surprisingly, the final oxidation step
      could be achieved using KMnO4 in THF to provide the Mn(iii) species 3 in high
      yield (91%). Both title compounds were structurally characterized by single
      crystal X-ray diffraction.

PMID- 29226938
TI  - Pd-Catalyzed C-H aziridination of 3,3,5,5-tetrasubstituted piperazin-2-ones.
AB  - A palladium mediated C-H aziridination reaction of 3,3,5,5-substituted-piperazin
      2-ones has been developed using phenyliodonium diacetate (PIDA) and succinic acid
      to give synthetically useful bicyclic aziridines, in moderate to good yields.
      Succinic acid was found to be key for selectively promoting C-N bond formation
      (aziridination) and suppressing competitive acetoxylation. Analysis of the
      reaction kinetics revealed the role of succinic acid in promoting an equilibrium
      between monomeric and dimeric palladium species in the rate determining step of
      the reaction. The aziridines can be ring-opened by nucleophiles under Lewis or
      Bronsted acidic conditions to give formal C-H functionalized products. The
      reaction conditions can be further manipulated to produce acetoxylated,
      diacetoxylated and even triacetoxylated materials through the use of acetic acid
      and increased oxidant stoichiometry.

PMID- 29226939
TI  - Studies of Agitation / Aggression in Alzheimer's Disease - Scientific and
      Operational Challenges.

PMID- 29226940
TI  - New IPA Criteria for Agitation in Cognitive Impairment.

PMID- 29226941
TI  - Trial Design for the Evaluation of Neuropsychiatric Symptoms in Alzheimer's
      Disease: Considerations and Recommendations.

PMID- 29226942
TI  - Post Hoc Evidence for an Additive Effect of Memantine and Donepezil: Consistent
      Findings from DOMINO-AD Study and Memantine Clinical Trial Program.
AB  - BACKGROUND: Several randomized trials have demonstrated superiority of memantine
      cholinesterase inhibitor combination therapy in patients with moderate to severe
      Alzheimer's disease, yet a recent publication reported no additional benefit of
      add-on memantine therapy compared to donepezil alone. OBJECTIVES: In this post
      hoc analysis, we sought to re-evaluate the results from the DOMINO study using
      common statistical tools and to apply the statistical models used in the DOMINO
      study to a pooled data set of 24- to 28-week randomized trials of memantine in
      patients with moderate to severe AD in order to explore the robustness of the
      primary findings from the DOMINO study. DESIGN: DOMINO study: Randomized, double
      blind, placebo-controlled trial (Current Controlled Trial number,
      ISRCTN49545035); Memantine Clinical Trial Program: Pooled analysis from four
      randomized, double-blind, placebo-controlled trials. SETTING: DOMINO study:
      United Kingdom; Memantine Clinical Trial Program: Multinational. PARTICIPANTS:
      DOMINO study: 295 participants enrolled during the period of February 2008 to
      March 2010; Memantine Clinical Trial Program: 1417 participants enrolled between
      August 1998 and January 2008. MEASUREMENTS: In the DOMINO study, the co-primary
      outcome measures were scores on the Standardized Mini-Mental State Examination
      and the Bristol Activities of Daily Living Scale; Neuropsychiatric Inventory was
      a secondary measure. In the Memantine Clinical Trial Program, outcome measures
      included the Severe Impairment Battery, the 19-item Alzheimer's Disease
      Cooperative Study - Activities of Daily Living scale, Neuropsychiatric Inventory,
      and a 4-Domain Composite Index (Z-score; a post hoc assessment). RESULTS: Both
      the pooled analysis of the Memantine Clinical Trial Program and the re-assessment
      of the DOMINO study with common statistical tools showed that adding memantine to
      donepezil therapy is associated with benefits across multiple clinical domains.
      CONCLUSIONS: The current analyses suggest that the results of the DOMINO study do
      not contradict previous studies which investigated the combined effects of
      memantine-cholinesterase inhibitor treatment.

PMID- 29226943
TI  - An Open-Label Trial of Yokukansan on Sleep Disturbance in Alzheimer's Disease and
      Other Dementia.
AB  - BACKGROUND: An effective hypnotic drug with a low risk of adverse reactions is
      required for Alzheimer's disease (AD) patients, because the therapeutic
      interventions to improve sleep quality may help alleviate some symptoms of AD
      including cognitive function. OBJECTIVE: The aim of this study was to investigate
      the efficacy and safety of Yokukansan in sleep disturbances in patients with AD
      and other dementia. DESIGN: An open-label trial. SETTING: Two sites consist of
      university and hospital in Japan. PARTICIPANTS: Thirteen patients (7 men and 6
      women, average age = 76.0 +/- 7.2 (mean +/- SD) years old) including 12 AD and 1
      frontotemporal dementia. INTERVENTION: Treatment with Yokukansan (5-7.5 g/day)
      was given for 8 weeks. MEASUREMENTS: The primary outcome measure was the Sleep
      Disorder Inventory (SDI) based on the Neuropsychiatric Inventory, an instrument
      developed by the Alzheimer's Disease Cooperative Study. Secondary outcome
      measures included the objective actigraphic evaluations, Neuropsychiatric
      Inventory-Questionnaire (NPI-Q), MINI-Mental State Examination (MMSE). These
      assessments were evaluated at baseline, and weeks 4 and 8. RESULTS: After 4 and 8
      weeks treatment with Yokukansan, significant improvements were observed in the
      SDI total score, caregivers' distress score, and NPI-Q total score. In actigraph
      data, wake after sleep onset (WASO) time (min), was significantly improved. The
      MMSE score did not change during the treatment. No serious adverse events were
      caused by YKS. CONCLUSION: The present results suggest that Yokukansan is safe
      and beneficial in the treatment of sleep disturbances and that it can possibly
      reduce the burden of care of demented patients.

PMID- 29226944
TI  - The Relationship of Hemoglobin Levels, Delirium and Cognitive Status in
      Hospitalized Geriatric Patients: Results from the CRIME Study.
AB  - OBJECTIVE: Delirium is a frequent clinical complication in geriatric patients
      admitted to the hospital, because of the simultaneous presence and synergistic
      effect of predisposing and precipitating factors. Also anaemia is a common
      concern in geriatric population. The aim of this study was to investigate the
      association between anaemia (precipitating factor) and delirium in a sample of
      Italian older hospitalized patients with different degree of cognitive impairment
      (predisposing factor). DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of
      1069 participants enrolled in the CRIME study, with assessment of hemoglobin
      levels at hospital admission. MEASUREMENTS: Delirium was assessed using DSM-IV
      criteria, whereas cognitive status was categorized as dementia, cognitive
      impairment or normal, according to clinical history, specific treatment and MMSE
      score. Anaemia was defined according to sex-specific WHO criteria. The
      association of hemoglobin levels and delirium was investigated with multivariable
      logistic regression models. RESULTS: Mean age of study participants was 81.4+/
      7.2 years, 52.2% had prevalent anaemia, 6.1% had delirium. According to cognitive
      status 20.8% had dementia and 40.9% had cognitive impairment. Overall there was
      no association between anaemia and delirium. However, among patients with
      cognitive impairment (MMSE <24, no dementia) anaemia was significantly associated
      with the likelihood of delirium (p<0.006). Multivariate logistic regression
      analysis, adjusted for potential confounders, showed in these patients a graded
      increased risk of delirium according to anaemia severity with an almost six-fold
      increased risk of delirium in moderate-severe anaemia (OR 5.95, 95% CI:1.15
      30.73). CONCLUSION: In older patients with cognitive impairment moderate-severe
      anaemia is independently associated with the likelihood of delirium. Further
      studies should investigate if anaemia correction would translate in delirium risk
      reduction.

PMID- 29226945
TI  - The Road Ahead To Cure And Prevent Alzheimer's Disease: Implementing Prevention
      into Primary Care.
AB  - Most old adults receive their health care from their primary care practitioner;
      as a consequence, as the population ages, the manifestations and complications of
      cognitive impairment and dementia impose a growing burden on providers of primary
      care. Current guidelines do not recommend routine cognitive screening for older
      persons by primary care physicians, although the vast majority recommend a
      cognitive status assessment and neurological examination for subjects with a
      cognitive complaint. Also, no clinical practice guidelines recommend
      interventions in older adults with cognitive impairment in primary care settings.
      However, primary care physicians need to conduct a review of risks and protective
      factors associated with cognitive decline and organize interventions to improve
      or maintain cognitive function. Recent epidemiological studies have indicated
      numerous associations between lifestyle-related risk factors and incidental
      cognitive impairment. The development of biomarkers could also help in diagnosis,
      prognosis, selection for clinical trials, and objective assessment of therapeutic
      responses. Interventions aimed at cognitive impairment prevention should be
      pragmatic and easy to implement on a large scale in different health care
      systems, without generating high additional costs or burden on participants,
      medical and social care teams.

PMID- 29226946
TI  - New Findings with Reanalysis of the Domino Trial ?

PMID- 29226947
TI  - Phenotype expansion and development in Kosaki overgrowth syndrome.
AB  - We expand the Kosaki overgrowth syndrome (KOGS) phenotype by over 70% to include
      24 unreported KOGS symptoms, in a first male patient, the third overall
      associated with the PDGFRB c.1751C>G p.(Pro584Arg) mutation. Eighteen of these
      symptoms are unique to our patient, the remaining six are shared with other
      patients. Of the 24 unreported features overall, 6 show marked phenotype
      evolution and varying time of onset. The triangular face detected at 14 months
      and long palpebral fissures with lateral ectropion at 4 years are present in
      other members of the cohort. The remaining 4 are unique to Patient 5: pronounced
      macrocephaly from birth, increasingly triangular anterior skull from 14 months,
      camptodactyly, emerging at 4 years and worsening joint contractures from 6 years.
      Compilation of all new symptoms reported here with published clinical data
      further identifies at least 18 clinical parameters common to all cases to date,
      encompassing both known KOGS-associated PDGFRB mutations. We therefore propose a
      set of 18 core KOGS symptoms, with 16 present in early childhood. These results
      should also impact diagnostic/prognostic scope, intervention and outcome
      potential for KOGS patients, particularly for developmentally progressive
      conditions such as scoliosis and myofibroma.

PMID- 29226948
TI  - MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low
      density lipoprotein via targeting toll-like receptor 4.
AB  - MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and
      abnormal expression of miR-182-5p has been involved in many diseases. However,
      the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our
      current investigation, an AS model was established by using oxidized low-density
      lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS
      model dose-dependently and time-dependently. Additionally, CD36, oil-red staining
      levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels,
      MDA, and cell apoptosis were also restrained with an enhancement of SOD activity.
      Consistently, opposite results were exhibited when miR-182-5p inhibitors were
      transfected into RAW264.7 cells. It is well known that toll-like receptor 4
      (TLR4) is responsible for many inflammation diseases. By using bioinformatics
      analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed
      TLR4 was activated in AS models and miR-182-5p could repress AS progression by
      targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played
      significant roles in AS through inhibiting oxidative stress and apoptosis via
      inactivating TLR4 expression.

PMID- 29226949
TI  - Thrombolysis for acute upper extremity deep vein thrombosis.
AB  - BACKGROUND: About 5% to 10% of all deep vein thromboses occur in the upper
      extremities. Serious complications of upper extremity deep vein thrombosis, such
      as post-thrombotic syndrome and pulmonary embolism, may in theory be avoided
      using thrombolysis. No systematic review has assessed the effects of thrombolysis
      for the treatment of individuals with acute upper extremity deep vein thrombosis.
      OBJECTIVES: To assess the beneficial and harmful effects of thrombolysis for the
      treatment of individuals with acute upper extremity deep vein thrombosis. SEARCH
      METHODS: The Cochrane Vascular Information Specialist (CIS) searched the
      Specialised Register (29 March 2017), the Cochrane Central Register of Controlled
      Trials (CENTRAL; 2017, Issue 2), and three trial registries (World Health
      Organization International Clinical Trials Registry, ClinicalTrials.gov, and
      ISRCTN registry) for ongoing and unpublished studies. We additionally searched
      the registries of the European Medical Agency and the US Food and Drug
      Administration (December 2016). SELECTION CRITERIA: We planned to include
      randomised clinical trials irrespective of publication type, publication date and
      language that investigated the effects of thrombolytics added to anticoagulation,
      thrombolysis versus anticoagulation, or thrombolysis versus any other type of
      medical intervention for the treatment of acute upper extremity deep vein
      thrombosis. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened all records to identify those that met inclusion criteria. We planned to
      use the standard methodological procedures expected by Cochrane. We planned to
      use trial domains to assess the risks of systematic error (bias) in the trials.
      We planned to conduct trial sequential analyses to control for the risk of random
      errors and to assess the robustness of our conclusions. We planned to consider a
      P value of 0.025 or less as statistically significant. We planned to assess the
      quality of the evidence using the GRADE approach. Our primary outcomes were
      severe bleeding, pulmonary embolism, and all-cause mortality. MAIN RESULTS: We
      found no trials eligible for inclusion. We also identified no ongoing trials.
      AUTHORS' CONCLUSIONS: There is currently insufficient evidence from which to draw
      conclusion on the benefits or harms of thrombolysis for the treatment of
      individuals with acute upper extremity deep vein thrombosis as an add-on therapy
      to anticoagulation, alone compared with anticoagulation, or alone compared with
      any other type of medical intervention. Large randomised clinical trials with a
      low risk of bias are warranted. They should focus on clinical outcomes and not
      solely on surrogate measures.

PMID- 29226950
TI  - Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights
      and therapeutic opportunities.
AB  - Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs)
      glycoproteins ubiquitously expressed on the cell surfaces and extracellular
      matrix of all mammalian tissues. There are four mammalian syndecans, SDC-1
      thorough 4, which play a critical role in cell adhesion, migration,
      proliferation, differentiation, and angiogenesis through independent and growth
      factor mediated signaling. An altered expression of SDCs is often observed in
      autoimmune disorders, cancer, HIV infection, and many other pathological
      conditions. SDCs modulate disease progression by interacting with a diverse array
      of ligands, receptors, and other proteins, including extracellular matrix,
      glycoproteins, integrins, morphogens, and various growth factors and chemokines,
      along with their receptors and kinases. Specifically, SDCs present on cell
      surface can bind directly to chemokines to enhance their binding to receptors,
      downstream signaling, and migration. Alternatively, SDCs can be cleaved and shed
      to mediate negative regulation of chemokine and growth factor signaling pathways
      and ligand sequestration. Importantly, SDC shedding may be a biomarker of
      inflammation, especially in chronic inflammatory diseases. While the current
      therapies for cancer and several autoimmune disorders have revolutionized
      treatment outcomes, understanding the pathophysiological role of SDCs and the use
      of HSPG mimetic or antagonists on cytokine signaling networks may uncover
      potentially novel targeted therapeutic approaches. This review mainly summarizes
      the current findings on the role of individual SDCs in disease processes,
      mechanisms through which SDCs mediate their biological functions, and the
      possibility of targeting SDCs as future potential therapeutic approaches.

PMID- 29226951
TI  - Cigarette smoke and non-neuronal cholinergic system in the airway epithelium of
      COPD patients.
AB  - Acetylcholine (ACh), synthesized by Choline Acetyl-Transferase (ChAT), exerts its
      physiological effects via mAChRM3 in epithelial cells. We hypothesized that
      cigarette smoke affects ChAT, ACh, and mAChRM3 expression in the airways from
      COPD patients promoting airway disease. ChAT, ACh, and mAChRM3 were assessed: "ex
      vivo" in the epithelium from central and distal airways of COPD patients, Healthy
      Smoker (S) and Healthy Subjects (C), and "in vitro" in bronchial epithelial cells
      stimulated with cigarette smoke extract (CSE). In central airways, mAChRM3, ChAT,
      and ACh immunoreactivity was significantly higher in the epithelium from S and
      COPD than in C subjects. mAChRM3, ChAT, and ACh score of immunoreactivity was
      high in the metaplastia area of COPD patients. mAChRM3/ChAT and ACh/ChAT co
      localization of immunoreactivity was observed in the bronchial epithelium from
      COPD. In vitro, CSE stimulation significantly increased mAChRM3, ChAT, and ACh
      expression and mAChRM3/ChAT and ACh/ChAT co-localization in 16HBE and NHBE, and
      increased 16HBE proliferation. Cigarette smoke modifies the levels of mAChMR3,
      ChAT expression, and ACh production in bronchial epithelial cells from COPD
      patients. Non-neuronal components of cholinergic system may have a role in the
      mechanism of bronchial epithelial cell proliferation, promoting alteration of
      normal tissue, and of related pulmonary functions.

PMID- 29226952
TI  - Differential expression of microRNAs let-7a, miR-125b, miR-100, and miR-21 and
      interaction with NF-kB pathway genes in periodontitis pathogenesis.
AB  - Periodontitis is a chronic inflammatory disease which is caused by destruction of
      the tissues that surrounds and supports the tooth. Deregulation of microRNAs has
      been reported to cause several inflammatory diseases such as autoimmune disease,
      chronic periodontitis, and cancer. In the present study, we have investigated the
      expression pattern of microRNAs let-7a, miR-125b, miR-100, miR-21, and RNA
      binding protein LIN-28A among healthy individuals and chronic periodontitis
      patients. Total RNA was isolated from gingival tissue samples collected from 100
      healthy individuals and 100 chronic periodontitis patients. The expression of
      microRNAs and LIN-28 was performed by qPCR. Target prediction for the microRNAs
      was done using miRWalk and miRTarbase online databases and the experimentally
      validated targets were analyzed for their molecular function, biological
      processes, and related pathways using gProfiler software. The expression analysis
      revealed that let-7a and miR-21 were upregulated, whereas, miR-100, miR-125b, and
      LIN-28 were down regulated. The age dependent expression analysis revealed that
      the expression levels of all the microRNAs and LIN-28 were found to increase with
      age (more than 50 years), thereby suggesting an increased risk to chronic
      periodontitis. Among the various targets predicted using miRWalk and miRTarbase
      databases, NFKB was found to be a common target among all the four microRNAs.
      gProfiler revealed several functions such as NF-KB signaling pathway, cytokine
      cytokine receptor interaction, osteoclast differentiation, etc., all of which
      specific to inflammation and periodontitis.

PMID- 29226953
TI  - MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers.
AB  - Melanoma is the leading cause of skin cancer deaths in the United States, and its
      incidence has been rising steadily for the past 30 years (Aftab, Dinger, &
      Perera, 2014). A more complete understanding of the molecular mechanisms that
      drive melanomagenesis is crucial to improve diagnosis, prognostication, and
      treatment of this disease. Given that melanoma survival rates are better when the
      disease is detected early, precise diagnostic tests for early melanoma detection
      would be extremely useful. In addition, as survival rates decrease drastically
      when the disease becomes metastatic, improved tools to more precisely identify
      high-risk patients as well as to predict treatment response are necessary. The
      role of microRNAs (miRNAs) in melanoma biology could be the key. miRNA expression
      profiling has identified several miRNAs that play a crucial role in melanoma cell
      proliferation, migration, and invasion, as well as miRNAs involved in apoptosis
      and in the immune response. Here we review the most current data on the miRNAs
      involved in melanoma as well as their potential roles as diagnostic and
      prognostic biomarkers of this disease.

PMID- 29226954
TI  - Effect of carrot puree in vegetable juice on linguapalatal swallowing pressure.
AB  - : This study aimed to ascertain the influence of various amounts (0-30%) of
      carrot puree (CP) in vegetable juice on linguapalatal swallowing pressure in
      healthy volunteers. Twenty healthy women (age range: 20-22 years) swallowed a 17
      ml drink in a natural state, and linguapalatal swallowing pressure was measured
      using a special sensor sheet. Peak magnitude (maximum pressure of the tongue
      pushing on the hard palate), integrated values of linguapalatal swallowing
      pressure on the waveform, and duration of linguapalatal swallowing pressure were
      increased with increases in CP concentrations. The total integrated value for 30%
      CP vegetable juice was larger than that of vegetable juice with no CP. The
      apparent viscosity of the vegetable juice with a low CP concentration was smaller
      than that with a high CP concentration at the same shear rate. These results
      suggest that vegetable juice containing CP affects mechanoreceptor activity in
      the mouth and generates a neuromotor response. PRACTICAL APPLICATIONS: This study
      aimed to ascertain the influence of various amounts of carrot puree (CP) in
      vegetable juice on linguapalatal swallowing pressure measured by using a special
      sensor sheet in healthy volunteers. Obtained results of this study clearly showed
      that vegetable juice containing CP affects the movement of the tongue in
      maneuvering the bolus. Moreover, the results demonstrated that this effect
      depended on the concentration of CP in the vegetable juice. These findings are
      expected to provide clinically valuable data on the effect of mechanical
      stimulation during the oral stage of swallowing.

PMID- 29226955
TI  - Stem cells rescue cardiomyopathy induced by P. gingivalis-LPS via miR-181b.
AB  - Systemic inflammation induced by bacterial infection is one of several causative
      agents for cardiovascular disorders in patients with periodontal disease.
      Experimental results indicate that miRNAs play important roles in systemic
      inflammation induced by endotoxins. Further evidence states that stem cell based
      therapy shows potential in the treatment of inflammatory responses induced by
      sepsis. This study investigates if stem cells show protective effects on
      cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through
      regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs)
      were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then
      rescued using adipose-derived stem cells (ADSC). The experimental results reveal
      that Pg-LPS treatment is capable of inducing TLR4/NFkappaB axis activation, cell
      death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated
      in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured
      with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central
      role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs
      cocultured with ADSC. miR181b acts as potential therapeutic marker in
      cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells
      show potential in the treatment of cardiomyopathy induced by porphyromonas
      gingivalis endotoxin via regulation of miR181b.

PMID- 29226956
TI  - Analysis of secreted peptidome from omental adipose tissue in polycystic ovarian
      syndrome patients.
AB  - Polycystic ovarian syndrome (PCOS) is a common endocrinopathy associated with
      increased risk of metabolic disorders. Prevalence of adiposity and obesity is
      greater in women suffering from PCOS. Moreover, adipose tissue dysfunction has
      been demonstrated in PCOS patients, particularly in abdominal adipose tissue.
      This dysfunction likely aggravates the metabolic and reproductive abnormalities.
      We used liquid chromatography-mass spectrometry to compare the peptides secreted
      from PCOS and non-PCOS abdominal adipose tissue. We detected 298 upregulated
      peptides and 31 downregulated peptides (absolute fold change >= 2 and p < 0.05).
      Twenty-nine peptides were only detected in the PCOS group, while 18 were only
      detected in the control group. In addition, we demonstrate that these cleavage
      products are not degradation products of the proteasome based on previous studies
      reported. Gene Ontology enrichment and pathway analysis were performed to study
      differentially secreted peptides through their precursor proteins. We identified
      12 peptides from 10 precursor proteins associated with PCOS, and 6 peptide
      sequences were located in the functional domains of their corresponding precursor
      proteins. These results provide a deeper understanding of adipose tissue-derived
      peptides in PCOS for future functional studies.

PMID- 29226957
TI  - Pilot multi-centre randomised trial of the impact of pre-operative focused
      cardiac ultrasound on mortality and morbidity in patients having surgery for
      femoral neck fractures (ECHONOF-2 pilot).
AB  - Hip fracture surgery is common, usually occurs in elderly patients who have
      multiple comorbidities, and is associated with high morbidity and mortality. Pre
      operative focused cardiac ultrasound can alter diagnosis and management, but its
      impact on outcome remains uncertain. This pilot study assessed feasibility and
      group separation for a proposed large randomised clinical trial of the impact of
      pre-operative focused cardiac ultrasound on patient outcome after hip fracture
      surgery. Adult patients requiring hip fracture surgery in four teaching hospitals
      in Australia were randomly allocated to receive focused cardiac ultrasound before
      surgery or not. The primary composite outcome was any death, acute kidney injury,
      non-fatal myocardial infarction, cerebrovascular accident, pulmonary embolism or
      cardiopulmonary arrest within 30 days of surgery. Of the 175 patients screened,
      100 were included as trial participants (screening:recruitment ratio 1.7:1), 49
      in the ultrasound group and 51 as controls. There was one protocol failure among
      those recruited. The primary composite outcome occurred in seven of the
      ultrasound group patients and 12 of the control group patients (relative group
      separation 39%). Death, acute kidney injury and cerebrovascular accident were
      recorded, but no cases of myocardial infarction, pulmonary embolism or
      cardiopulmonary arrest ocurred. Focused cardiac ultrasound altered the management
      of 17 participants, suggesting an effect mechanism. This pilot study demonstrated
      that enrolment and the protocol are feasible, that the primary composite outcome
      is appropriate, and that there is a treatment effect favouring focused cardiac
      ultrasound - and therefore supports a large randomised clinical trial.

PMID- 29226958
TI  - Masking exposure to phobic stimuli reduces fear without inducing electrodermal
      activity.
AB  - A series of experiments has shown that limiting awareness of exposure to feared
      stimuli through visual masking-or very brief exposure (VBE)-reduces avoidance of
      a live tarantula by spider-phobic participants. We investigated this process of
      fear reduction by directly relating the effects of VBE on electrodermal activity
      to its ensuing effects on phobic behavior. Sixty spider-phobic participants,
      identified by approaching a live tarantula and a questionnaire, were administered
      either VBE to masked spiders or control exposure to masked flowers. Skin
      conductance levels (SCLs) were continuously recorded during exposure. The
      participants approached the tarantula again immediately thereafter. VBE reduced
      avoidance of the tarantula and did not increase SCLs or cause subjective distress
      relative to control exposure. SCL increases during VBE were strongly negatively
      correlated with the reduction of self-reported fear of the tarantula: the less
      that SCLs increased during VBE, the more it reduced fear. VBE only increased SCLs
      in participants whose fear was not reduced; it did not increase SCLs in
      participants whose fear of the tarantula was reduced. Awareness of the stimuli
      did not mediate these effects. Control exposure did not yield any of these
      effects. In a second experiment, clearly visible exposure to spider images
      increased SCLs and subjective distress more than both VBE and control exposure,
      whereas VBE did not increase SCLs or subjective distress relative to control
      exposure within the same spider-phobic participants. These findings suggest that
      exposure to phobic images can reduce fear even when it bypasses the induction of
      electrodermal activity.

PMID- 29226960
TI  - An adaptive orienting theory of error processing.
AB  - The ability to detect and correct action errors is paramount to safe and
      efficient goal-directed behaviors. Existing work on the neural underpinnings of
      error processing and post-error behavioral adaptations has led to the development
      of several mechanistic theories of error processing. These theories can be
      roughly grouped into adaptive and maladaptive theories. While adaptive theories
      propose that errors trigger a cascade of processes that will result in improved
      behavior after error commission, maladaptive theories hold that error commission
      momentarily impairs behavior. Neither group of theories can account for all
      available data, as different empirical studies find both impaired and improved
      post-error behavior. This article attempts a synthesis between the predictions
      made by prominent adaptive and maladaptive theories. Specifically, it is proposed
      that errors invoke a nonspecific cascade of processing that will rapidly
      interrupt and inhibit ongoing behavior and cognition, as well as orient attention
      toward the source of the error. It is proposed that this cascade follows all
      unexpected action outcomes, not just errors. In the case of errors, this cascade
      is followed by error-specific, controlled processing, which is specifically aimed
      at (re)tuning the existing task set. This theory combines existing predictions
      from maladaptive orienting and bottleneck theories with specific neural
      mechanisms from the wider field of cognitive control, including from error
      specific theories of adaptive post-error processing. The article aims to describe
      the proposed framework and its implications for post-error slowing and post-error
      accuracy, propose mechanistic neural circuitry for post-error processing, and
      derive specific hypotheses for future empirical investigations.

PMID- 29226961
TI  - Detection of deception: Event-related potential markers of attention and
      cognitive control during intentional false responses.
AB  - Successful deception requires the coordination of multiple mental processes, such
      as attention, conflict monitoring, and the regulation of emotion. We employed a
      simple classification task, assessing ERPs to further investigate the attentional
      and cognitive control components of (instructed) deception. In Experiment 1, 20
      participants repeatedly categorized visually presented names of five animals and
      five plants. Prior to the experiment, however, each participant covertly selected
      one animal and one plant for deliberate misclassification. For these critical
      items, we observed significantly increased response times (RTs), error rates, and
      amplitudes of three ERP components: anterior P3a indicating the processing of
      task relevance, medial-frontal negativity reflecting conflict monitoring, and
      posterior P3b indicating sustained visual attention. In a blind identification of
      the individual critical words based on a priori defined criteria, an algorithm
      using two behavioral and two ERP measures combined showed a sensitivity of 0.73
      and a specificity of 0.95, thus performing far above chance (0.2/0.2). Experiment
      2 used five clothing and five furniture names and successfully replicated the
      findings of Experiment 1 in 25 new participants. For detection of the critical
      words, the algorithm from Experiment 1 was reused with only slight adjustments of
      the ERP time windows. This resulted in a very high detection performance
      (sensitivity 0.88, specificity 0.94) and significantly outperformed an algorithm
      based on RT alone. Thus, at least under controlled laboratory conditions, a
      highly accurate detection of instructed lies via the attentional and cognitive
      control components is feasible, and benefits strongly from combined behavioral
      and ERP measures.

PMID- 29226959
TI  - Larvivorous fish for preventing malaria transmission.
AB  - BACKGROUND: Adult female Anopheles mosquitoes can transmit Plasmodium parasites
      that cause malaria. Some fish species eat mosquito larvae and pupae. In disease
      control policy documents, the World Health Organization (WHO) includes biological
      control of malaria vectors by stocking ponds, rivers, and water collections near
      where people live with larvivorous fish to reduce Plasmodium parasite
      transmission. In the past, the Global Fund has financed larvivorous fish
      programmes in some countries, and, with increasing efforts in eradication of
      malaria, policymakers may return to this option. Therefore, we assessed the
      evidence base for larvivorous fish programmes in malaria control. OBJECTIVES: To
      evaluate whether introducing larvivorous fish to anopheline larval habitats
      impacts Plasmodium parasite transmission. We also sought to summarize studies
      that evaluated whether introducing larvivorous fish influences the density and
      presence of Anopheles larvae and pupae in water sources. SEARCH METHODS: We
      searched the Cochrane Infectious Diseases Group Specialized Register; the
      Cochrane Central Register of Controlled Trials (CENTRAL), published in the
      Cochrane Library; MEDLINE (PubMed); Embase (Ovid); CABS Abstracts; LILACS; and
      the metaRegister of Controlled Trials (mRCT) up to 6 July 2017. We checked the
      reference lists of all studies identified by the search. We examined references
      listed in review articles and previously compiled bibliographies to look for
      eligible studies. Also we contacted researchers in the field and the authors of
      studies that met the inclusion criteria for additional information regarding
      potential studies for inclusion and ongoing studies. This is an update of a
      Cochrane Review published in 2013. SELECTION CRITERIA: Randomized controlled
      trials (RCTs) and non-RCTs, including controlled before-and-after studies,
      controlled time series, and controlled interrupted time series studies from
      malaria-endemic regions that introduced fish as a larvicide and reported on
      malaria in the community or the density of the adult anopheline population. In
      the absence of direct evidence of an effect on transmission, we performed a
      secondary analysis on studies that evaluated the effect of introducing
      larvivorous fish on the density or presence of immature anopheline mosquitoes
      (larvae and pupae forms) in water sources to determine whether this intervention
      has any potential that may justify further research in the control of malaria
      vectors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      each article by title and abstract, and examined potentially relevant studies for
      inclusion using an eligibility form. At least two review authors independently
      extracted data and assessed risk of bias of included studies. If relevant data
      were unclear or were not reported, we contacted the study authors for
      clarification. We presented data in tables, and we summarized studies that
      evaluated the effects of introducing fish on anopheline immature density or
      presence, or both. We used the GRADE approach to summarize the certainty of the
      evidence. We also examined whether the included studies reported any possible
      adverse impact of introducing larvivorous fish on non-target native species. MAIN
      RESULTS: We identified no studies that reported the effects of introducing
      larvivorous fish on the primary outcomes of this review: malaria infection in
      nearby communities, entomological inoculation rate, or on adult Anopheles
      density.For the secondary analysis, we examined the effects of introducing
      larvivorous fish on the density and presence of anopheline larvae and pupae in
      community water sources, and found 15 small studies with a follow-up period
      between 22 days and five years. These studies were undertaken in Sri Lanka (two
      studies), India (three studies), Ethiopia (one study), Kenya (two studies), Sudan
      (one study), Grande Comore Island (one study), Korea (two studies), Indonesia
      (one study), and Tajikistan (two studies). These studies were conducted in a
      variety of settings, including localized water bodies (such as wells, domestic
      water containers, fishponds, and pools (seven studies); riverbed pools below dams
      (two studies)); rice field plots (five studies); and water canals (two studies).
      All included studies were at high risk of bias. The research was insufficient to
      determine whether larvivorous fish reduce the density of Anopheles larvae and
      pupae (12 studies, unpooled data, very low certainty evidence). Some studies with
      high stocking levels of fish seemed to arrest the increase in immature anopheline
      populations, or to reduce the number of immature anopheline mosquitoes, compared
      with controls. However, this finding was not consistent, and in studies that
      showed a decrease in immature anopheline populations, the effect was not always
      consistently sustained. In contrast, some studies reported larvivorous fish
      reduced the number of water sources withAnopheles larvae and pupae (five studies,
      unpooled data, low certainty evidence).None of the included studies reported
      effects of larvivorous fish on local native fish populations or other species.
      AUTHORS' CONCLUSIONS: We do not know whether introducing larvivorous fish reduces
      malaria transmission or the density of adult anopheline mosquito populations.In
      research studies that examined the effects on immature anopheline stages of
      introducing fish to potential malaria vector larval habitats, high stocking
      levels of fish may reduce the density or presence of immature anopheline
      mosquitoes in the short term. We do not know whether this translates into impact
      on malaria transmission. Our interpretation of the current evidence is that
      countries should not invest in fish stocking as a stand alone or supplementary
      larval control measure in any malaria transmission areas outside the context of
      research using carefully controlled field studies or quasi-experimental designs.
      Such research should examine the effects on native fish and other non-target
      species.

PMID- 29226962
TI  - EEG frequency PCA in EEG-ERP dynamics.
AB  - Principal components analysis (PCA) has long been used to decompose the ERP into
      components, and these mathematical entities are increasingly accepted as
      meaningful and useful representatives of the electrophysiological components
      constituting the ERP. A similar expansion appears to be beginning in regard to
      decomposition of the EEG amplitude spectrum into frequency components via
      frequency PCA. However, to date, there has been no exploration of the brain's
      dynamic EEG-ERP linkages using PCA decomposition to assess components in each
      measure. Here, we recorded intrinsic EEG in both eyes-closed and eyes-open
      resting conditions, followed by an equiprobable go/no-go task. Frequency PCA of
      the EEG, including the nontask resting and within-task prestimulus periods, found
      seven frequency components within the delta to beta range. These differentially
      predicted PCA-derived go and no-go N1 and P3 ERP components. This demonstration
      suggests that it may be beneficial in future brain dynamics studies to implement
      PCA for the derivation of data-driven components from both the ERP and EEG.

PMID- 29226963
TI  - Retraction: Pu, S., Zhao, Y., Zhou, G., Zhu, H., Gong, L., Zhang, W., Huang, G.,
      Wang, D. and Liu, D., Effect of CDK1 shRNA on proliferation, migration, cell
      cycle and apoptosis in non-small cell lung cancer. J. Cell. Physiol. Accepted
      Author Manuscript. doi: 10.1002/jcp.26387.
AB  - The above article from the Journal of Cellular Physiology, published online on 11
      December 2017 in Wiley Online Library as an Accepted Article, has been withdrawn
      by agreement between the authors, the journal Editor in Chief, Gary Stein and
      Wiley Periodicals, Inc. The withdrawal has been agreed because the article has
      been submitted for publication without the consent of all authors.

PMID- 29226964
TI  - Quantifying the contribution of mass flow to nitrogen acquisition by an
      individual plant root.
AB  - The classic model of nitrogen (N) flux into roots is as a Michaelis-Menten (MM)
      function of soil-N concentration at root surfaces. Furthermore, soil-N transport
      processes that determine soil-N concentration at root surfaces are seen as a
      bottleneck for plant nutrition. Yet, neither the MM relationship nor soil-N
      transport mechanisms are represented in current terrestrial biosphere models.
      Processes governing N supply to roots - diffusion, mass flow, N immobilization by
      soil microbes - are incorporated in a model of root-N uptake. We highlight a
      seldom considered interaction between these processes: nutrient traverses the
      rhizosphere more quickly in the presence of mass flow, reducing the probability
      of its immobilization before reaching the root surface. Root-N uptake is
      sensitive to the rate of mass flow for widely spaced roots with high N uptake
      capacity, but not for closely spaced roots or roots with low uptake capacity. The
      results point to a benefit of root switching from high- to low-affinity N
      transport systems in the presence of mass flow. Simulations indicate a strong
      impact of soil water uptake on N delivery to widely spaced roots through
      transpirationally driven mass flow. Furthermore, a given rate of N uptake per
      unit soil volume may be achieved by lower root biomass in the presence of mass
      flow.

PMID- 29226965
TI  - Brain reflections: A circuit-based framework for understanding information
      processing and cognitive control.
AB  - Here, I propose a view of the architecture of the human information processing
      system, and of how it can be adapted to changing task demands (which is the
      hallmark of cognitive control). This view is informed by an interpretation of
      brain activity as reflecting the excitability level of neural representations,
      encoding not only stimuli and temporal contexts, but also action plans and task
      goals. The proposed cognitive architecture includes three types of circuits: open
      circuits, involved in feed-forward processing such as that connecting stimuli
      with responses and characterized by brief, transient brain activity; and two
      types of closed circuits, positive feedback circuits (characterized by sustained,
      high-frequency oscillatory activity), which help select and maintain
      representations, and negative feedback circuits (characterized by brief, low
      frequency oscillatory bursts), which are instead associated with changes in
      representations. Feed-forward activity is primarily responsible for the spread of
      activation along the information processing system. Oscillatory activity,
      instead, controls this spread. Sustained oscillatory activity due to both local
      cortical circuits (gamma) and longer corticothalamic circuits (alpha and beta)
      allows for the selection of individuated representations. Through the interaction
      of these circuits, it also allows for the preservation of representations across
      different temporal spans (sensory and working memory) and their spread across the
      brain. In contrast, brief bursts of oscillatory activity, generated by novel
      and/or conflicting information, lead to the interruption of sustained oscillatory
      activity and promote the generation of new representations. I discuss how this
      framework can account for a number of psychological and behavioral phenomena.

PMID- 29226967
TI  - Gender-specific expression of GIBBERELLIC ACID INSENSITIVE is critical for
      unisexual organ initiation in dioecious Spinacia oleracea.
AB  - While unisexual flowers have evolved repeatedly throughout angiosperm families,
      the actual identification of sex-determining genes has been elusive, and their
      regulation within populations remains largely undefined. Here, we tested the
      mechanism of the feminization pathway in cultivated spinach (Spinacia oleracea),
      and investigated how this pathway may regulate alternative sexual development. We
      tested the effect of gibberellic acid (GA) on sex determination through exogenous
      applications of GA and inhibitors of GA synthesis and proteasome activity. GA
      concentrations in multiple tissues were estimated by enzyme-linked immunosorbent
      assay analysis. Gene function was investigated and pathway analysis was performed
      through virus-induced gene silencing. Relative gene expression levels were
      estimated by quantitative reverse transcription-polymerase chain reaction.
      Inhibition of GA production and proteasome activity feminized male flowers.
      However, there was no difference in GA content in tissues between males and
      females. We characterized a single DELLA family transcription factor gene
      (GIBBERELLIC ACID INSENSITIVE (SpGAI)) and observed inflorescence expression in
      females two-fold higher than in males. Reduction of SpGAI expression in females
      to male levels phenocopied exogenous GA application with respect to flower
      development. These results implicate SpGAI as the feminizing factor in spinach,
      and suggest that the feminizing pathway is epistatic to the masculinizing
      pathway. We present a unified model for alternative sexual development and
      discuss the implications for established theory.

PMID- 29226966
TI  - Using trial-level data and multilevel modeling to investigate within-task change
      in event-related potentials.
AB  - EEG data, and specifically the ERP, provide psychologists with the power to
      examine quickly occurring cognitive processes at the native temporal resolution
      at which they occur. Despite the advantages conferred by ERPs to examine
      processes at different points in time, ERP researchers commonly ignore the trial
      to-trial temporal dimension by collapsing across trials of similar types (i.e.,
      the signal averaging approach) because of constraints imposed by repeated
      measures ANOVA. Here, we present the advantages of using multilevel modeling
      (MLM) to examine trial-level data to investigate change in neurocognitive
      processes across the course of an experiment. Two examples are presented to
      illustrate the usefulness of this technique. The first demonstrates decreasing
      differentiation in N170 amplitude to faces of different races across the course
      of a race categorization task. The second demonstrates attenuation of the ERN as
      participants commit more errors within a task designed to measure implicit racial
      bias. Although the examples presented here are within the realm of social
      psychology, the use of MLM to analyze trial-level EEG data has the potential to
      contribute to a number of different theoretical domains within psychology.

PMID- 29226968
TI  - Study of microRNAs targeted Dvl2 on the osteoblasts differentiation of rat BMSCs
      in hyperlipidemia environment.
AB  - Dishevelled 2 (Dvl-2), a key mediator of the wnt/beta-catenin signaling pathway,
      plays critical roles in osteoblasts differentiation in hyperlipidemia
      environment. In our previous study, we observed a strong correlation between
      increased dvl2 expression and decreased new bone formation around implants in a
      rat hyperlipidemia implant surgery model. However, transcriptional regulation of
      Dvl2 by microRNAs in this process remains unknown. In the current study, we
      searched in online database and identified four significantly up-regulated
      miRNAs, miR-21-5p, miR-29c-3p, miR-138-5p, and miR-351-5p that could potentially
      regulate Dvl2. Using Western blot and dual-luciferase assays, we confirmed that
      miR29c-3p suppresses Dvl2 expression by binding to its 3'-UTR. Our results
      suggest a novel transcriptional regulation mechanism of Dvl2 by miR-29c-3p in
      osteoblasts differentiation of BMSCs.

PMID- 29226969
TI  - Cudratricusxanthone A attenuates sepsis-induced liver injury via SIRT1 signaling.
AB  - Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the
      roots of Cudraniatricuspidata Bureau, is known to possess antithrombotic,
      antiproliferative, and antiinflammatory activities. It remains unclear that CTXA
      can improve hepatoprotective activity in vivo. The objective of this study was to
      investigate the effect of CTXA on lipopolysaccharide (LPS)-induced liver failure
      in mice, and to elucidate its underlying molecular mechanisms. Liver failure was
      induced by LPS (15 mg/kg, i.p.) in mice, and 12 hr later, they were treated
      intravenously with CTXA. Administration of LPS significantly increased mortality,
      serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and
      serum inflammatory cytokines. CTXA treatment effectively countered these effects
      of LPS. Further, LPS treatment markedly increased the expression of
      myeloperoxidase, phosphorylation of p38, extracellular signal-regulated kinase
      (ERK), and c-Jun N-terminal kinase (JNK), and expressions of nuclear proteins,
      such as nuclear factor (NF)-kappaB and phosphorylated c-Jun. Additionally, LPS
      increased the serum levels of tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6. All these effects of LPS were attenuated by CTXA. Moreover, CTXA
      increased the expression of sirtuin-1 (SIRT1) and reduced the expression of
      acetylated forkhead box O1 box O1 (Ac-FoxO1), acetylated Ac-p53, and acetylated
      nuclear factor-kappa beta (Ac-NF-kappaB). In conclusion, CTXA alleviates LPS
      induced liver injury by reducing inflammatory responses and the potential
      mechanism is associated with SIRT1 signaling activation and finally could be used
      to treat liver diseases.

PMID- 29226971
TI  - Intravenous dexamethasone for prophylaxis of postoperative nausea and vomiting
      after administration of long-acting neuraxial opioids: a systematic review and
      meta-analysis.
AB  - Long-acting neuraxial opioids provide excellent analgesia after surgery, but are
      associated with higher rates of postoperative nausea and vomiting. Dexamethasone
      effectively prevents postoperative nausea and vomiting after general anaesthesia,
      but its value in patients receiving long-acting neuraxial opioids is
      undetermined. Therefore, the objective of this meta-analysis was to assess the
      prophylactic anti-emetic efficacy of intravenous (i.v.) dexamethasone in this
      population. The study methodology followed the PRISMA statement guidelines. The
      primary outcome was the need for rescue anti-emetics during the first 24
      postoperative hours, analysed according to the dose of dexamethasone (low-dose
      2.5-5.0 mg; intermediate dose 6.0-10.0 mg), timing of administration (beginning
      or end of surgery) and route of long-acting opioid administration (intrathecal or
      epidural). Additionally, the rates of complications (restlessness, infection,
      hyperglycaemia) were sought. Thirteen trials were identified, representing a
      total of 1111 patients. When compared with placebo, intravenous dexamethasone
      reduced the need for rescue anti-emetics (risk ratio (95%CI) 0.44 (0.35-0.56); I2
      = 43%; p < 0.00001; quality of GRADE evidence: moderate), without differences
      between dexamethasone doses (p for sub-group difference = 0.67), timing of
      administration (p for sub-group difference = 0.32) or route of long-acting opioid
      (p for sub-group difference = 0.10). No patients developed infection or
      restlessness among trials that sought these complications. No trial measured
      blood glucose levels. In conclusion, there is enough evidence to state that
      intravenous dexamethasone provides effective anti-emetic prophylaxis during the
      first 24 postoperative hours in patients who receive long-acting neuraxial
      opioids.

PMID- 29226970
TI  - A dominant-interfering camta3 mutation compromises primary transcriptional
      outputs mediated by both cell surface and intracellular immune receptors in
      Arabidopsis thaliana.
AB  - Pattern recognition receptors (PRRs) and nucleotide-binding domain and leucine
      rich repeat (LRR)-containing proteins (NLRs) initiate pattern-triggered immunity
      (PTI) and effector-triggered immunity (ETI), respectively, each associated with
      the activation of an overlapping set of defence genes. The regulatory mechanism
      behind this convergence of PTI- and ETI-mediated defence gene induction remains
      elusive. We generated transgenic Arabidopsis plants that enable conditional NLR
      activation without pathogen infection to dissect NLR- and PRR-mediated
      transcriptional signals. A comparative analysis of over 40 transcriptome datasets
      linked calmodulin-binding transcription activators (CAMTAs) to the activation of
      overlapping defence genes in PTI and ETI. We used a dominant camta3 mutant
      (camta3-D) to assess CAMTA functions in the corresponding transcriptional
      regulation. Transcriptional regulation by NLRs, although highly similar to PTI
      responses, can be established independently of pathogen-associated molecular
      pattern (PAMP) perception, defence phytohormones and host cell death. Conditional
      expression of the N-terminal coiled-coil domain of the barley MLA (Mildew
      resistance locus A) NLR is sufficient to trigger similar transcriptional
      reprogramming as full-length NLRs. CAMTA-binding motifs are overrepresented in
      the 5' regulatory regions of the identified primary immune response genes,
      consistent with their altered expression and disease resistance responses in
      camta3-D plants. We propose that CAMTA-mediated transcriptional regulation
      defines an early convergence point in NLR- and PRR-mediated signalling.

PMID- 29226972
TI  - Physiological acclimation dampens initial effects of elevated temperature and
      atmospheric CO2 concentration in mature boreal Norway spruce.
AB  - Physiological processes of terrestrial plants regulate the land-atmosphere
      exchange of carbon, water, and energy, yet few studies have explored the
      acclimation responses of mature boreal conifer trees to climate change. Here we
      explored the acclimation responses of photosynthesis, respiration, and stomatal
      conductance to elevated temperature and/or CO2 concentration ([CO2 ]) in a 3-year
      field experiment with mature boreal Norway spruce. We found that elevated [CO2 ]
      decreased photosynthetic carboxylation capacity (-23% at 25  degrees C) and
      increased shoot respiration (+64% at 15  degrees C), while warming had no
      significant effects. Shoot respiration, but not photosynthetic capacity,
      exhibited seasonal acclimation. Stomatal conductance at light saturation and a
      vapour pressure deficit of 1 kPa was unaffected by elevated [CO2 ] but
      significantly decreased (-27%) by warming, and the ratio of intercellular to
      ambient [CO2 ] was enhanced (+17%) by elevated [CO2 ] and decreased (-12%) by
      warming. Many of these responses differ from those typically observed in
      temperate tree species. Our results show that long-term physiological acclimation
      dampens the initial stimulation of plant net carbon assimilation to elevated [CO2
      ], and of plant water use to warming. Models that do not account for these
      responses may thus overestimate the impacts of climate change on future boreal
      vegetation-atmosphere interactions.

PMID- 29226973
TI  - Metal-citrate complex transport in Kineococcus radiotolerans.
AB  - The growth of an organism is highly dependent on the acquisition of carbon and
      metals, and availability of these nutrients in the environment affects its
      survival. Organisms can obtain both nutrients simultaneously through proteins of
      the CitMHS superfamily. Bioinformatic studies suggested a CitMHS gene (Accession
      number ABS03965.1) in Kineococcus radiotolerans. Radio flux assays following 14-C
      radiolabelled citrate, either free or complexed to a variety of metal ions, in K.
      radiotolerans demonstrated internalization of the citrate when bound to select
      metal ions only, primarily in the form of calcium-citrate. A pH response was also
      observed, consistent with a permease (ATP independent) mechanism as noted for
      other CitMHS family members, with greater uptake at pH 7 compared to pH 10. These
      results confirm the ability of K. radiotolerans to transport complexed citrate.

PMID- 29226974
TI  - Acute bronchiolitis: Influence of viral co-infection in infants hospitalized over
      12 consecutive epidemic seasons.
AB  - Bronchiolitis is the first lower respiratory tract viral infection manifesting in
      infants younger than 12 months of age. Our aim was to evaluate clinical and
      serological differences in infants with bronchiolitis from a single or from
      multiple viruses. Our secondary aim was to investigate differences in recurrent
      wheezing episodes after 12-24-36 months of follow-up. We reviewed the clinical
      records for 486 full-term infants hospitalized for bronchiolitis with at least
      one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one
      virus was detected and in 55 (11.3%) infants more than one virus was found. No
      differences were observed in the length of hospitalization, clinical severity
      score, O2 supplementation or admission to the intensive care unit. Single virus
      was associated with higher serum C-reactive protein (C-RP) than infants with
      multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus
      (RSV) was the most frequently detected virus. RSV alone was associated with
      higher C-RP (P = 0.007), compared to RSV coinfection. Infants with human
      rhinovirus (hRV) alone had higher white blood cell counts, higher blood
      neutrophils, and higher serum C-RP levels than hRV co-infection (P = 0.029, P =
      0.008, P = 0.008). RSV + hRV, the most frequent co-infection, was associated with
      lower neutrophil count and lower C-RP levels (P = 0.008, P = 0.016) and less
      fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences
      were found in the frequency of recurrent wheezing between single versus multiple
      viruses after bronchiolitis. Our findings suggest that in infants with
      bronchiolitis multiple viral co-infections can occur, without influence in the
      clinical severity of the disease. Infants with co-infection seems to mount a
      lower inflammatory response.

PMID- 29226975
TI  - Mathematical modeling and simulation in animal health. Part III: Using nonlinear
      mixed-effects to characterize and quantify variability in drug pharmacokinetics.
AB  - A common feature of human and veterinary pharmacokinetics is the importance of
      identifying and quantifying the key determinants of between-patient variability
      in drug disposition and effects. Some of these attributes are already well known
      to the field of human pharmacology such as bodyweight, age, or sex, while others
      are more specific to veterinary medicine, such as species, breed, and social
      behavior. Identification of these attributes has the potential to allow a better
      and more tailored use of therapeutic drugs both in companion and food-producing
      animals. Nonlinear mixed effects (NLME) have been purposely designed to
      characterize the sources of variability in drug disposition and response. The
      NLME approach can be used to explore the impact of population-associated
      variables on the relationship between drug administration, systemic exposure, and
      the levels of drug residues in tissues. The latter, while different from the
      method used by the US Food and Drug Administration for setting official
      withdrawal times (WT) can also be beneficial for estimating WT of approved animal
      drug products when used in an extralabel manner. Finally, NLME can also prove
      useful to optimize dosing schedules, or to analyze sparse data collected in
      situations where intensive blood collection is technically challenging, as in
      small animal species presenting limited blood volume such as poultry and fish.

PMID- 29226976
TI  - Analysis of variation in virulence of Beauveria bassiana against insect pests of
      pigeonpea using qPCR.
AB  - Beauveria bassiana is a broad spectrum microbial bioagent used for the control of
      agriculturally important insect pests. However, in our experiments, two virulent
      isolates of B. bassiana (B2 and B10) showed specific preference toward Maruca
      vitrata and Helicoverpa armigera of pigeonpea. To better understand this feature,
      we developed a qPCR assay to quantify the chitinase (virulence factor) of B.
      bassiana during the infection process. Isolates of B. bassiana were grown on
      insect cuticle amended medium and minimal medium (without insect cuticle) to
      assess the induction of chitinase. Our results revealed a positive correlation
      between expression of chitinase by B. bassiana and the substrates (with or
      without cuticles of M. vitrata and H. armigera) used. This study showcases the
      methodology to quantify the chitinase and analysis of variation in virulence of
      B. bassiana (B2 and B10) against M. vitrata and H. armigera.

PMID- 29226977
TI  - Mechanical responses of the mechanosensitive unstructured domains in cardiac
      titin.
AB  - BACKGROUND INFORMATION: Titin is one of the three main filaments in cardiac
      sarcomere. Besides a chain of Ig domains, cardiac titin also contains a proline
      (P), glutamate (E), valine (V), lysine (K) (PEVK) domain and a cardiac-specific
      N2B domain, both are largely unstructured. While they are believed to be involved
      in the elastic (PEVK and N2B) and the trophic (N2B) functions of the heart, their
      mechanical responses in physiological level of forces remains poorly understood.
      RESULTS: In order to gain understanding on their mechanical responses, we used
      magnetic tweezers to investigate their force responses from 1 to 30 pN. We
      confirmed that in vitro the PEVK domain is intrinsically disordered within the
      force range. Surprisingly, we discovered a mechanosensitive folded element in the
      disordered region of N2B, ~84 amino acids in length, which has a large folding
      energy of approximately -10 kB T. Based on the force responses of PEVK and N2B
      domains, as well as an approximated force-dependent unfolding and refolding rates
      of titin Ig domains, we show that the tension in cardiac titin fluctuates within
      5 pN during cardiac contraction and extension cycle using Gillespie simulation
      algorithm. Exceptionally, the simulation shows that deletion of N2B domain
      results in 10-fold increase in peak force. CONCLUSION: Our results highlight a
      critical role that N2B may potentially play in regulating tension on cardiac
      titin. SIGNIFICANCE: The study provides new insights into the tension regulatory
      role of unstructured domains in the elastic function of the heart, which has
      broad implication in diastolic dysfunction and cardiac trophic mechanisms. In
      addition, the method can be applied to probing other unstructured
      mechanosensitive proteins/domains.

PMID- 29226979
TI  - It Is Time to Re-Evaluate the Peer Review Process for Preclinical Research.
AB  - Problems in peer review, the backbone of maintaining high standards in scientific
      publishing, have led to wide spread discontent within the scientific community.
      Training in the peer review process and a simpler format to assist in decision
      making are possible courses to improve and expedite the process of peer review
      and scientific publishing.

PMID- 29226978
TI  - Simultaneous determination of residues of metalaxyl, cyazofamid and a cyazofamid
      metabolite in tobacco leaves and soil by liquid chromatography with tandem mass
      spectrometry.
AB  - A simple method was developed and validated for the simultaneous determination of
      metalaxyl, cyazofamid and the cyazofamid metabolite 4-chloro-5-p-tolylimidazole-2
      carbonitrile (CCIM) by liquid chromatography with tandem mass spectrometry. The
      three target compounds were extracted from tobacco and soil with acetonitrile
      containing 0.1% acetic acid, and the extracts were purified using
      octadecylsilane. The proposed method showed satisfactory linearity (R2 >= 0.9985)
      for the target compounds. The limits of detection for metalaxyl, cyazofamid and
      CCIM were 0.006, 0.06 and 0.06 mg/kg in soil and green tobacco leaves and 0.03,
      0.3 and 0.3 mg/kg in cured tobacco leaves, respectively. The limits of
      quantification for metalaxyl, cyazofamid and CCIM were 0.02, 0.2 and 0.2 mg/kg in
      soil and green tobacco leaves and 0.1, 1 and 1 mg/kg in cured tobacco leaves,
      respectively. The average recoveries from soil and tobacco were 72.91-98.40% for
      metalaxyl, 76.73-105.80% for cyazofamid and 74.48-106.45% for CCIM. The relative
      standard deviation range was 1.23-6.99%. The developed method was successfully
      applied to analysis of residues of metalaxyl, cyazofamid and CCIM in real soil
      and tobacco samples. The results indicated that the established method could meet
      the requirement for the analysis of trace amounts of all three analytes in soil
      and tobacco.

PMID- 29226981
TI  - Aggressive cutaneous squamous cell carcinoma arising from a human papillomavirus
      infected epidermoid cyst of the conchal bowl.

PMID- 29226982
TI  - Actikerall: an alternative to curettage for some seborrhoeic keratoses?

PMID- 29226980
TI  - Follicular papules and pustules in a patient with pulmonary symptoms.

PMID- 29226983
TI  - Combing Chromosomal DNA Mediated by the SMC Complex: Structure and Mechanisms.
AB  - Genome maintenance requires various nucleoid-associated factors in prokaryotes.
      Among them, the SMC (Structural Maintenance of Chromosomes) protein has been
      thought to play a static role in the organization and segregation of the
      chromosome during cell division. However, recent studies have shown that the
      bacterial SMC is required to align left and right arms of the emerging chromosome
      and that the protein dynamically travels from origin to Ter region. A rod form of
      the SMC complex mediates DNA bridging and has been recognized as a machinery
      responsible for DNA loop extrusion, like eukaryotic condensin or cohesin
      complexes, which act as chromosome organizers. Attention is now turning to how
      the prototype of the complex is loaded on the entry site and translocated on
      chromosomal DNA, explaining its overall conformational changes at atomic levels.
      Here, we review and highlight recent findings concerning the prokaryotic SMC
      complex and discuss possible mechanisms from the viewpoint of protein
      architecture.

PMID- 29226984
TI  - A novel homozygous mutation disrupting the initiation codon in the SLURP1 gene
      underlies mal de Meleda in a consanguineous family.
AB  - Mal de Meleda (MDM) is a palmoplantar keratoderma (PPK), characterized by
      hyperkeratosis of the palms and soles, and keratotic skin lesions. Patients with
      MDM can develop perioral erythema, keratotic and lichenoid plaques over the
      joints (including the elbows and knees), nail abnormalities, joint contractures
      and stiffness, brachydactyly, sclerodactyly, pseudoainhum, and malodorous
      maceration. MDM is associated with mutations in the SLURP1 gene. We report a
      consanguineous family in which MDM was inherited in an autosomal recessive
      manner. Genotyping using microsatellite markers established linkage in the family
      to the SLURP1 gene, which has been mapped previously to chromosome 8q24.3.
      Sequence analysis revealed a homozygous missense mutation (c.2T>C, p.Met1Thr) in
      affected family members. Molecular docking studies using a ZDOCK server predicted
      disruption of binding of the mutant variant to its target alpha7-nAChR. This
      study further supports the previously reported findings that homozygous mutations
      in the SLURP1 gene cause MDM.

PMID- 29226986
TI  - Vaccination of Atlantic lumpfish (Cyclopterus lumpus L.) at a low temperature
      leads to a low antibody response against Aeromonas salmonicida.
AB  - We present a study on the effect of water temperature on immunization of Atlantic
      lumpfish. In total, 360 fish were vaccinated with either 50 MUl of an oil-based
      injection vaccine (VAX), with Aeromonas salmonicida and Vibrio salmonicida
      antigens, or PBS. Fish were vaccinated at three different water temperatures, 5
      degrees C, 10 degrees C and 15 degrees C, and sorted into six groups (N = 60).
      Lumpfish were weighed every 3 weeks after vaccination, sampled at 3, 6, 9 and 18
      weeks post-immunization (wpi) and evaluated by modified Speilberg score, ELISA
      and immunoblotting. Vaccinated fish showed low antibody response against V.
      salmonicida. Fish vaccinated at 5 degrees C showed significantly lower antibody
      response against A. salmonicida throughout the study. At higher temperatures,
      vaccinated fish showed significantly increased antibody responses, at 18 wpi for
      10 degrees C and at 6 and 18 wpi for 15 degrees C. Immunoblotting demonstrated
      specific response against the LPS antigen of A. salmonicida in the 10 degrees C
      and 15 degrees C VAX groups. Mean body weight increased in all groups throughout
      the study. Vaccinated fish had low Speilberg scores with no melanization of
      abdominal tissue. Our results show that vaccinating lumpfish at a lower water
      temperature may lead to a low antibody response against A. salmonicida.

PMID- 29226987
TI  - Protective effect of platelet-rich plasma on urethral injury model of male rats.
AB  - AIMS: Urethral stricture (US) formation is caused by fibrosis after excessive
      collagen formation following an injury or trauma to the urethra. In this study,
      we aimed to evaluate the effects of platelet-rich plasma (PRP) on a urethral
      injury (UI) model of male rats. METHODS: A UI model was used by applying a
      coagulation current to the urethras of male rats. There were four groups with six
      rats in each: control group, PRP applied to naive urethra, UI group, and UI with
      PRP application. PRP was applied to the urethra after a coagulation current
      induced injury as soon as possible. On the 14th day, all rats were sacrificed and
      urethral tissues were investigated for collagen type I, collagen type III,
      platelet-derived growth factor-alpha, platelet-derived growth factor-beta, and
      transforming growth factor-beta using quantitative real-time polymerase chain
      reaction and Western blot analysis. The effect of urethral damage and healing was
      evaluated for collagen type I-to-collagen type III ratio. RESULTS: The collagen
      type I-to-collagen type III ratio was significantly higher in UI group (P < 0.05)
      than in the others, while UI with PRP application group had comparable results
      with the control group (P > 0.05). CONCLUSIONS: The results of this study show
      that PRP has a preventive effect on stricture formation in a UI model of rats, as
      shown by its effect on collagen synthesis. Further studies that eventually show
      the effects of PRP on human tissues are necessary and promising.

PMID- 29226988
TI  - CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: a
      comparison with its counterparts in the kidney and soft tissue.
AB  - Central nervous system high-grade neuroepithelial tumors with BCOR alteration
      (CNS HGNET-BCOR) are a recently reported rare entity, identified as a small
      fraction of tumors previously institutionally diagnosed as so-called CNS
      primitive neuroectodermal tumors. Their genetic characteristic is a somatic
      internal tandem duplication in the 3' end of BCOR (BCOR ITD), which has also been
      found in clear cell sarcomas of the kidney (CCSK) and soft tissue
      undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of
      infancy (URCS/PMMTI), and these BCOR ITD-positive tumors have been reported to
      share similar pathological features. In this study, we performed a
      clinicopathological and molecular analysis of six cases of CNS HGNET-BCOR, and
      compared them with their counterparts in the kidney and soft tissue. Although
      these tumors had histologically similar structural patterns and characteristic
      monotonous nuclei with fine chromatin, CNS HGNET-BCOR exhibited glial cell
      morphology, ependymoma-like perivascular pseudorosettes and palisading necrosis,
      whereas these features were not evident in CCSK or URCS/PMMTI.
      Immunohistochemically, diffuse staining of Olig2 with a mixture of varying
      degrees of intensity, and only focal staining of GFAP, S-100 protein and
      synaptophysin were observed in CNS HGNET-BCOR, whereas these common
      neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although
      CNS HGNET-BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD-positive
      tumors, only CNS HGNET-BCOR has histological features suggestive of glial
      differentiation. In conclusion, we think CNS HGNET-BCOR are a certain type of
      neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI
      occurring in the CNS.

PMID- 29226989
TI  - Transcriptome characterization of male accessory glands in ants to identify
      molecules involved in their reproductive success.
AB  - In insects, seminal fluid proteins that are produced by male accessory glands and
      transferred to females during mating have key functions in sperm competition and
      sperm physiology that lead to male reproductive success. In ants, male
      reproductive success also depends on the longevity of sperm stored in the queen's
      spermatheca because their sexual offspring are usually produced only after a
      prolonged storage period. We identified genes that were up-regulated in the male
      accessory glands relative to the bodies of Crematogaster osakensis to
      characterize the reproductive molecules associated with male reproductive success
      in ants. We found novel genes that had no hits in a homology search and that were
      predominantly expressed in the accessory glands. These reproductive proteins may
      have evolved under rapid positive selection for reproductive success in the
      species. Furthermore, we discovered that three spermatheca-specific genes of C.
      osakensis queens were also enriched in the accessory glands relative to the
      bodies of males. These genes may be important for maintaining the sperm quality
      continuously from ejaculation by males to prolonged storage by queens. This
      research provides crucial information about the molecular mechanisms of sperm
      maintenance and sexual selection in ants, and also insight into the evolution of
      reproductive strategies in insects.

PMID- 29226990
TI  - A Novel Reconfigurable Logic Unit Based on the DNA-Templated Potassium
      Concentration-Dependent Supramolecular Assembly.
AB  - Plenty of molecular circuits with specific functions have been developed;
      however, logic units with reconfigurability, which could simplify the circuits
      and speed up the information process, are rarely reported. In this work, we
      designed a novel reconfigurable logic unit based on a DNA-templated, potassium
      concentration-dependent, supramolecular assembly, which could respond to the
      input stimuli of H+ and K+ . By inputting different concentrations of K+ , the
      logic unit could implement three significant functions, including a half adder, a
      half subtractor, and a 2-to-4 decoder. Considering its reconfigurable ability and
      good performance, the novel prototypes developed here may serve as a promising
      proof of principle in molecular computers.

PMID- 29226991
TI  - Vitellogenin and its receptor play essential roles in the development and
      reproduction of the brown citrus aphid, Aphis (Toxoptera) citricidus.
AB  - Vitellogenin (Vg) and its receptor (VgR) play a key role in the reproductive
      process and development of insects. Aphids are a group of high-fecundity insect
      species with pseudoplacental viviparity, but the roles of their Vg and VgR genes
      have not been investigated yet. The brown citrus aphid, Aphis (Toxoptera)
      citricidus, is a major insect pest of citrus and the main vector of Citrus
      tristeza closterovirus. In this study, we identified and characterized these two
      genes, designated as AcVg and AcVgR, from the brown citrus aphid. We found that
      AcVg has lost the DUF1943 domain that is present in other insect Vgs. Silencing
      of AcVg and AcVgR led to a delay in the nymph-adult transition, a prolonged
      prereproductive period, and a shortened reproductive period, which in turn
      resulted in slower embryonic development and fewer new-born nymphs.
      Interestingly, silencing of AcVg decreased the transcript level of AcVgR, but
      silencing of AcVgR resulted in increased transcript levels of AcVg. In addition,
      silencing of Vg/VgR had similar phenotypes between alate and apterous morphs,
      suggesting that the functions of these two genes are the same in the two wing
      morphs of the aphid. Our results demonstrate that Vg and VgR are involved in
      various aspects of aphid development and reproduction. Further studies on the
      synthesis of Vg could help to elucidate the reproductive mechanism and provide
      information that will be useful for developing new pest control strategies.

PMID- 29226992
TI  - Solid-phase organic synthesis of chiral, non-racemic 1,2,4-trisubstituted 1,4
      diazepanes with high sigma1 receptor affinity.
AB  - The aim of this work was to transfer the established chiral-pool synthesis of
      1,2,4-trisubstituted 1,4-diazepanes in solution on the solid phase. For this
      purpose, (S)-configured amino acids, (S)-alanine, and (S)-leucine, with a small
      methyl and a larger isobutyl moiety were attached to the solid support 9 by
      reductive amination. After five reaction steps on the solid support, the 1,4
      diazepanes (S)-19a,b were cleaved off and reductively alkylated to afford the
      1,2,4-trisubstituted 1,4-diazepanes (S)-20a and (S)-21b, respectively. Both
      compounds show high sigma1 affinity and selectivity over the sigma2 subtype.

PMID- 29226993
TI  - Genetic polymorphisms of microRNA machinery genes predict overall survival of
      esophageal squamous carcinoma.
AB  - BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs)
      in miRNA processing machinery genes are implicated in carcinogenesis, as they
      change the expression profiles of miRNA. Six miR-SNPs in miRNA processing
      machinery genes, including Dicer (rs3742330), RAN (rs14035), XPO5 (rs11077),
      TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), were evaluated for
      their association with esophageal squamous cell carcinoma (ESCC). METHODS: The
      miR-SNP of the miRNA processing genes were genotyped using the polymerase chain
      reaction-ligase detection reaction (PCR-LDR) assay, while the XPO5 expression
      levels in ESCC tissues were measured by immunochemistry methods. RESULTS:
      Patients carrying the rs11077 AA allele exhibited a significantly increased
      lifespan than AC+CC carriers, as determined by univariate and multivariate
      analyses (relative risk: 2.490; 95% confidence interval [CI]: 1.225-5.058;
      P=.012). Furthermore, the rs11077 AA genotype displayed a trend for high XPO5
      expression in ESCC tissues by immunochemistry analysis, and these high XPO5
      expression levels were also associated with high survival rates among ESCC
      patients. CONCLUSION: Our results suggested that the miRNA machinery gene
      expression-associated miR-SNPs would modify cancer outcomes; in this light, XPO5
      may be an important new target for ESCC therapy.

PMID- 29226994
TI  - Demographic and clinical correlates of accelerometer assessed physical activity
      and sedentary time in lung cancer survivors.
AB  - OBJECTIVE: To determine demographic and clinical correlates of accelerometer
      assessed physical activity and sedentary time among a population-based sample of
      lung cancer survivors. METHODS: Lung cancer survivors in Southern Alberta, Canada
      (N = 527) were invited to complete a mailed survey assessing socio-demographics
      and wear an Actigraph(r) GT3X+ accelerometer for 7 days. Average daily minutes of
      physical activity and sedentary time were derived from the accelerometer data.
      Accelerometer data were processed using standard Freedson cutpoints, and
      correlates of physical activity and sedentary time were determined with linear
      regression. RESULTS: A total of 127 lung cancer survivors participated (mean age
      = 71 years), for a 24% response rate. Moderate-to-vigorous physical activity was
      negatively associated with being >60 years of age (beta = -7.4, CI: -14.7, 
      0.10). Moderate-to-vigorous physical activity accumulated in 10-minute bouts was
      associated with receiving surgery and adjuvant chemotherapy (beta = 9.1, CI: 2.1,
      16.1). Sedentary time was associated with being >60 years of age (beta = 32.4,
      CI: 3.1, 61.7), smoking (beta = 63.9, CI: 22.5, 105.4), and being
      overweight/obese (beta = 28.6, CI: 6.4, 50.1). CONCLUSION: Age, smoking history,
      and body mass index emerged as correlates of accelerometer assessed light,
      moderate, and vigorous physical activity, and sedentary time among lung cancer
      survivors. IMPLICATIONS FOR CANCER SURVIVORS: Identifying correlates of physical
      activity and sedentary time may aid in the development of targeted behavioral
      interventions for this population.

PMID- 29226995
TI  - Change in QRS morphology as a marker of spontaneous elimination in verapamil
      sensitive idiopathic left ventricular tachycardia.
AB  - BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia
      (verapamil-ILVT) is thought to be due to a reentry within the LV fascicular
      system. Radiofrequency catheter ablation (RFCA) is effective for elimination of
      the VT; however, a long-term prognosis of patients with verapamil-ILVT is still
      unclear. METHODS AND RESULTS: Eighty consecutive verapamil-ILVT patients (62 men,
      31 +/- 12 years of age, LVEF: 65 +/- 4%) were enrolled. Seventy-six (95%) cases
      of VT involved right bundle branch block and left axis deviation. We
      retrospectively analyzed changes in the QRS duration (DeltaQRS-d) and QRS axis
      (DeltaQRS-axis) during follow-up and compared them with recurrence of VT. During
      a mean follow-up period of 10 years (2-32 years), no sudden death or heart
      failure occurred. Fifty-one (64%) patients underwent RFCA, and 46 (90%) of them
      had no VT without any medication after RFCA. The DeltaQRS-d (16 +/- 2 vs. 8 +/- 1
      ms, P = 0.24) and DeltaQRS-axis (20 +/- 4 vs. 4 +/- 3 degrees, P = 0.23) were not
      different in patients with no VT (VT[-]) and those with recurrence of VT (VT[+]).
      However, in the remaining 29 patients without RFCA, VT was spontaneously
      eliminated in 16 patients. The DeltaQRS-d (30 +/- 6 vs. 6 +/- 1 ms, P = 0.002)
      and DeltaQRS-axis (23 +/- 4 vs. 5 +/- 2 degrees, P = 0.001) were significantly
      larger in VT(-) patients compared to VT(+) patients during follow-up.
      CONCLUSIONS: Some verapamil-ILVT patients who show QRS morphology changes over
      the follow-up period may become free from VT without any invasive or
      pharmacological treatments, suggesting that further altered LV fascicular
      conduction might eliminate the reentry of verapamil-ILVT.

PMID- 29226996
TI  - Breast and gynecological cancer patients' risk factors associated with
      biopsychosocial problem-related distress.
AB  - OBJECTIVES: Inequalities exist between breast and gynecological cancer patients'
      experiences, leading to high levels of distress throughout the cancer journey.
      The present study aims to identify differences in source of biopsychosocial
      problem-related distress between women diagnosed with breast or gynecological
      cancers. METHODS: From 2009 to 2016, women with breast (n = 2111) and
      gynecological (n = 641) cancers were screened using the core items of the
      instrument You, Your Family, and City of Hope are a Team. This is a touch screen
      based instrument that assess problem-related distress due to physical, practical,
      functional, emotional, and other problems and identifies types of assistance
      requested. Data were analyzed using the linear regression model. RESULTS: A
      significant difference in overall biopsychosocial problems rated as high distress
      was found between breast (M = 5.0) and gynecological (M = 6.2) cancer patients (P
      < .001). Gynecological cancer patients endorsed a greater number of problems to
      talk with a member of the team (alone or with written information), while both
      cancer groups requested written information equally. Gynecological cancer was
      associated with higher physical, functional, emotional, and total distress.
      Younger patients, non-Asian, and those with lower education and lower household
      income also reported greater distress. CONCLUSIONS: Gynecological cancer patients
      represent a high-risk group, reporting greater problem-related distress and
      higher levels of requested assistance. Age, education, race/ethnicity, and income
      were found to be potential risk factors. Findings highlight the importance of
      considering characteristics and special needs related to specific types of cancer
      to assist in the effective treatment of distress throughout the continuum of
      care.

PMID- 29226997
TI  - Participation and interest in support services among family caregivers of older
      adults with cancer.
AB  - OBJECTIVE: The purpose of this study was to describe distressed and underprepared
      family caregiver's use of and interest in formal support services (eg,
      professional counseling, education, organizational assistance). METHOD: Cross
      sectional mail survey conducted in communities of 8 cancer centers in Tennessee,
      Alabama, and Florida (response rate: 42%). Family caregivers of Medicare
      beneficiaries with pancreatic, lung, brain, ovarian, head and neck, hematologic,
      and stage IV cancers reported support service use and completed validated
      measures of depression, anxiety, burden, preparedness, and health. RESULTS:
      Caregivers (n = 294) were on average age 65 years and mostly female (73%), White
      (91%), and care recipients' spouse/partner (60%); patients averaged 75 years were
      majority male (54%) with lung cancer (39%). Thirty-two percent of caregivers
      reported accessing services while 28% were "mostly" or "extremely" interested.
      Thirty-five percent of caregivers with high depressive symptoms (n = 122), 33%
      with high anxiety symptoms (n = 100), and 25% of those in the lowest quartile of
      preparedness (n = 77) accessed services. Thirty-eight percent of those with high
      depressive symptoms, 47% with high anxiety symptoms, and 36% in the lowest
      quartile of preparedness were "mostly" or "extremely" interested in receiving
      services. Being interested in support services was significantly associated with
      being a minority, shorter durations of caregiving, and with higher stress burden.
      CONCLUSIONS: A large proportion of family caregivers, including those
      experiencing depression and anxiety symptoms and who were underprepared, are not
      using formal support services but have a strong interest in services. Strategies
      to increase service use may include targeting distressed caregivers early in
      their caregiving experience.

PMID- 29226999
TI  - Comparison of outcomes between postpartum and non-postpartum women with stress
      urinary incontinence treated with conservative therapy: A prospective cohort
      study.
AB  - AIM: This study aimed to compare the outcomes of pelvic floor muscle training
      (PFMT) between postpartum and non-postpartum women with stress urinary
      incontinence (SUI) and to detect potential factors that may influence these
      outcomes. METHODS: A total of 54 and 79 participants were recruited into
      postpartum (PP group) and non-postpartum (non-PP group) groups, respectively. A
      physiotherapist treated the participants twice a week for 6-8 weeks. At baseline
      and 6 and 12 months after treatment, the 1-h pad weight test (PWT), vaginal
      contraction pressure (VCP), and Incontinence Impact Questionnaire Short Form (IIQ
      7) were assessed by an evaluator or physiotherapist. The primary outcome was PWT
      improvement. The participants whose PWT improvement reached a >50% reduction
      relative to baseline were considered responders. Secondary outcomes included VCP,
      IIQ-7 score, and patient satisfaction rate. RESULTS: The PWT improvement was
      87.04% (95%CI: 0.78, 0.96) in the PP group at 1-year follow-up, which was
      significantly better than the 72.15% improvement (95%CI: 0.62, 0.82) in the non
      PP group (OR = 2.591, 95%CI: 1.018, 6.595, P = 0.041). Changes in VCP and BMI
      were significant predictors of responders in the regression analysis. As the
      change in VCP increased by 1 cmH2 O, the efficiency increased by 4.2% (OR =
      1.042, 95%CI: 1.010, 1.070). The change in BMI increased by 1 kg/m2 , and the
      efficiency decreased 23.0% (OR = 0.770, 95%CI: 0.633, 0.937). CONCLUSIONS: The
      outcome of PFMT in postpartum participants with SUI was better than that in non
      postpartum participants. Women with more improvements in VCP and weight loss
      showed better amelioration of SUI symptoms after PFMT.

PMID- 29226998
TI  - Antisense suppression of glial fibrillary acidic protein as a treatment for
      Alexander disease.
AB  - OBJECTIVE: Alexander disease is a fatal leukodystrophy caused by autosomal
      dominant gain-of-function mutations in the gene for glial fibrillary acidic
      protein (GFAP), an intermediate filament protein primarily expressed in
      astrocytes of the central nervous system. A key feature of pathogenesis is
      overexpression and accumulation of GFAP, with formation of characteristic
      cytoplasmic aggregates known as Rosenthal fibers. Here we investigate whether
      suppressing GFAP with antisense oligonucleotides could provide a therapeutic
      strategy for treating Alexander disease. METHODS: In this study, we use GFAP
      mutant mouse models of Alexander disease to test the efficacy of antisense
      suppression and evaluate the effects on molecular and cellular phenotypes and non
      cell-autonomous toxicity. Antisense oligonucleotides were designed to target the
      murine Gfap transcript, and screened using primary mouse cortical cultures. Lead
      oligonucleotides were then tested for their ability to reduce GFAP transcripts
      and protein, first in wild-type mice with normal levels of GFAP, and then in
      adult mutant mice with established pathology and elevated levels of GFAP.
      RESULTS: Nearly complete and long-lasting elimination of GFAP occurred in brain
      and spinal cord following single bolus intracerebroventricular injections, with a
      striking reversal of Rosenthal fibers and downstream markers of microglial and
      other stress-related responses. GFAP protein was also cleared from cerebrospinal
      fluid, demonstrating its potential utility as a biomarker in future clinical
      applications. Finally, treatment led to improved body condition and rescue of
      hippocampal neurogenesis. INTERPRETATION: These results demonstrate the efficacy
      of antisense suppression for an astrocyte target, and provide a compelling
      therapeutic approach for Alexander disease. Ann Neurol 2018;83:27-39.

PMID- 29227000
TI  - Oligonucleotides Incorporating Palladacyclic Nucleobase Surrogates.
AB  - An oligonucleotide incorporating a palladacyclic nucleobase has been prepared by
      ligand-directed metalation of a phenylpyridine moiety. This oligonucleotide
      hybridized with natural counterparts placing any of the canonical nucleobases
      opposite to the palladacyclic residue. The palladated duplexes had B-type
      conformation and melting temperatures comparable to those of respective
      unmodified duplexes with a single mismatch. In the duplexes placing C, G or T
      (but not A) opposite to the palladacyclic residue, greatly increased absorptivity
      suggested formation of a PdII -mediated base pair. Absorptivity and ellipticity
      of these duplexes persisted even at the highest temperatures applicable in Tm and
      CD experiments (90  degrees C). Evidently the PdII -mediated base pairs do not
      dissociate under the experimental conditions.

PMID- 29227001
TI  - Antiviral therapy for hepatitis B virus during second pregnancies.
AB  - Mother-to-child transmission of the hepatitis B virus (HBV) is a major concern
      for infected mothers, especially after their first child has become an HBV
      carrier despite immunoprophylaxis. Eight mothers whose first child had become an
      HBV carrier despite immunoprophylaxis were referred for antiviral therapy during
      the subsequent pregnancy. All pregnant women were seropositive for both the
      hepatitis B surface antigen and hepatitis B e antigen. In the treatment group
      (three receiving lamivudine and two receiving tenofovir), mother-to-child
      transmission of the HBV was successfully prevented in all infants (5/5). On the
      other hand, two of three infants became HBV carriers in the untreated group.
      There were no significant adverse effects in either mothers or infants. Antiviral
      therapy using lamivudine and tenofovir during the second pregnancy successfully
      prevented mother-to-child transmission of the HBV for high-risk mothers.

PMID- 29227002
TI  - Cerebral sex dimorphism and sexual orientation.
AB  - The neurobiology of sexual orientation is frequently discussed in terms of
      cerebral sex dimorphism (defining both functional and structural sex
      differences). Yet, the information about possible cerebral differences between
      sex-matched homo and heterosexual persons is limited, particularly among women.
      In this multimodal MRI study, we addressed these issues by investigating possible
      cerebral differences between homo and heterosexual persons, and by asking whether
      there is any sex difference in this aspect. Measurements of cortical thickness
      (Cth), subcortical volumes, and functional and structural resting-state
      connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF)
      were compared with those of 30 homosexual males (HoM) and 30 homosexual females
      (HoF). Congruent with previous reports, sex differences were detected in
      heterosexual controls with regard to fractional anisotropy (FA), Cth, and several
      subcortical volumes. Homosexual groups did not display any sex differences in FA
      values. Furthermore, their functional connectivity was significantly less
      pronounced in the mesial prefrontal and precuneus regions. In these two
      particular regions, HoM also displayed thicker cerebral cortex than other groups,
      whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed
      "sex-reversed" values, not observed in HoF. Homosexual orientation seems
      associated with a less pronounced sexual differentiation of white matter tracts
      and a less pronounced functional connectivity of the self-referential networks
      compared to heterosexual orientation. Analyses of Cth suggest that male and
      female homosexuality are not simple analogues of each other and that differences
      from heterosexual controls are more pronounced in HoM.

PMID- 29227003
TI  - Association between end-stage diabetic nephropathy and MTHFR (C677T and A1298C)
      gene polymorphisms.
AB  - AIM: Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of
      homocysteine metabolism. The C677T and A1298C polymorphism of the MTHFR gene has
      been reported to be associated with elevated plasma homocysteine in patients with
      Diabetic nephropathy. This study aimed to investigate the influence of the C677T
      and A1298C polymorphisms on the progression chronic kidney disease in diabetic
      nephropathy of south Indian population. METHODS: We genotyped 145 DN cases and
      100 controls for the C677T and A1298C polymorphisms using PCR-RFLP based
      protocols, and all diabetic nephropathy cases divided into two groups based on
      CKD stages: 60 DN cases were early stage (CKD1 to CKD3) and 85 DN cases were
      advanced stage (CKD4 and CKD5). Association chi2 and univariate analysis were
      performed. RESULTS: The C677T (OR=4.2; 95% CI=2.31-7.64 and p=0.001) and A1298C
      (OR=2.8; 95% CI=1.05-7.57 and p=0.033) polymorphism was shown that the
      significant association between the cases and control. Furthermore, the MTHFR
      gene polymorphism C677T (OR=2.48; 95% CI=1.25-4.9 and p=0.008) was observed that
      the significant contribution of the progression of CKD in DN. CONCLUSION: These
      findings suggest that the C677T and A1298C polymorphism of MTHFR gene was
      associated with diabetic nephropathy in south Indian population. Furthermore, the
      present study provides evidence that the C677T polymorphism was associated with
      CKD progression in DN.

PMID- 29227004
TI  - Recurrence of uterine myoma after myomectomy: Open myomectomy versus laparoscopic
      myomectomy.
AB  - AIM: Open myomectomy (OM) was previously frequently performed; however,
      laparoscopic myomectomy (LM) has recently become more common. Nevertheless, myoma
      can recur after both LM and OM. In this study, we report our retrospective
      investigation of myoma recurrence by comparing LM and OM. METHODS: A total of 474
      patients underwent LM and 279 patients underwent OM. The patients were followed
      up postoperatively from six months to eight years. Recurrence was confirmed when
      a myoma with a diameter of >= 1 cm was detected. Post-LM, post-OM and cumulative
      recurrence rates were investigated, and a Cox hazard test was performed. RESULTS:
      The cumulative recurrence rates between the two groups were 76.2% (LM) vs. 63.4%
      (OM) at eight years postoperatively. A log-rank test revealed a significant
      difference between the two groups. Cox hazard testing revealed that LM, a larger
      number of enucleated myoma masses and the absence of postoperative gestation
      significantly contributed to the postoperative recurrence rate. CONCLUSIONS: LM
      yielded a higher recurrence rate than OM, likely a result of manual myoma removal
      in OM, which is a more exhaustive extraction of smaller myoma masses than
      performed in LM. In other words, fewer residual myoma masses after OM contribute
      to a lower postoperative recurrence rate.

PMID- 29227005
TI  - Extracellular matrix remodeling and TGF-beta1/Smad signaling in diabetic colon
      mucosa.
AB  - Diabetes is associated with metabolic and functional alterations in the gut.
      Using an experimental model of streptozotocin (STZ)-induced diabetes in rodents,
      we analyzed the extracellular matrix (ECM) and TGF-beta/Smad signaling in the
      colon mucosa. Male rats were divided into normal control, diabetic and insulin
      treated diabetic groups during 4 and 9 weeks. Sirius red staining showed marked
      increase in the extracellular matrix deposition in diabetic mucosa. High levels
      of fibrillar collagen (I and III) and fibronectin mRNAs were also detected with
      an imbalance between MMPs/TIMPs activities. Moreover, an increased mesenchymal
      cell proliferation together with an enhanced expression of myofibroblasts markers
      vimentin and alpha-SMA were observed. TGF-beta/Smad signaling-related genes were
      determined using RT-PCR, Western blotting, and immunohistochemistry. Diabetic
      rats showed a significant up-regulation of TGF-beta1, TGF-beta receptors and the
      effectors p-Smad2/3 in the mucosa compared with control rats. Insulin treatment
      attenuated the stimulating effect of diabetes on colon ECM deposition and TGF
      beta/Smad signaling. In conclusion, the overall results showed a deregulation of
      the TGFbeta1 pathway associated with the appearance of myofibroblasts and the
      accumulation of ECM in the mucosa of diabetic colon. These data provide the first
      in vivo evidence that TGF-beta1/Smad is a key component of intestinal tissue
      remodeling in diabetes.

PMID- 29227006
TI  - Major improvement in the detection of microsatellite instability in colorectal
      cancer using HSP110 T17 E-ice-COLD-PCR.
AB  - Every colorectal cancer (CRC) patient should be tested for microsatellite
      instability (MSI) to screen for Lynch syndrome. Evaluation of MSI status involves
      screening tumor DNA for the presence of somatic deletions in DNA repeats using
      PCR followed by fragment analysis. While this method may lack sensitivity due to
      the presence of a high level of germline DNA, which frequently contaminates the
      core of primary colon tumors, no other method developed to date is capable of
      modifying the standard PCR protocol to achieve improvement of MSI detection.
      Here, we describe a new approach developed for the ultra-sensitive detection of
      MSI in CRC based on E-ice-COLD-PCR, using HSP110 T17, a mononucleotide DNA repeat
      previously proposed as an optimal marker to detect MSI in tumor DNA, and an
      oligo(dT)16 LNA blocker probe complementary to wild-type genotypes. The HT17 E
      ice-COLD-PCR assay improved MSI detection by 20-200-fold compared with standard
      PCR using HT17 alone. It presents an analytical sensitivity of 0.1%-0.05% of
      mutant alleles in wild-type background, thus greatly improving MSI detection in
      CRC samples highly contaminated with normal DNA. HT17 E-ice-COLD-PCR is a rapid,
      cost-effective, easy-to-implement, and highly sensitive method, which could
      significantly improve the detection of MSI in routine clinical testing.

PMID- 29227007
TI  - Self-Assembly Process of a Pd2 L4 Capsule: Steric Interactions between
      Neighboring Components Favor the Formation of Large Intermediates.
AB  - The effect of molecular interactions between the components on the self-assembly
      process of Pd2 L4 structures was investigated by a 1 H NMR-based quantitative
      approach (QASAP: quantitative analysis of self-assembly process). Although the
      self-assembly of the Pd2 L4 cage without interactions between the bent ligands
      took place, mainly producing small intermediates, the self-assembly of the Pd2 L4
      capsule composed of bent ligands with anthracene panels tends to produce large
      intermediates containing more components than the capsule. This is ascribed to
      steric interactions between the panels.

PMID- 29227008
TI  - Ice or fire? Comparison of second-generation cryoballoon ablation and
      radiofrequency ablation in patients with symptomatic persistent atrial
      fibrillation and an enlarged left atrium.
AB  - INTRODUCTION: We aimed to compare arrhythmia recurrence rates after second
      generation cryoballoon (CB-Adv) ablation and radiofrequency (RF) ablation in
      patients with symptomatic persistent atrial fibrillation (AF) and left atrial
      (LA) enlargement. METHODS AND RESULTS: Persistent AF patients with LA enlargement
      were compared using a propensity-score-matching algorithm, and 111 patients
      treated with CB-Adv ablation and 111 patients treated with RF ablation were
      selected. The primary endpoint was the first documented >30-second arrhythmia
      recurrence after a 3-month blanking period. Median LA area was comparable between
      the RF and CB-Adv groups (24.2 vs. 24.0 cm2 , P = 0.49). In addition to pulmonary
      vein isolation, roof lines (RLs) with bidirectional conduction block were created
      in 48 patients in the CB-Adv group and 49 patients in the RF group. Midterm
      outcome after single procedure is characterized by arrhythmia recurrences in 47
      patients in the RF group and 32 patients in the CB-Adv group (P = 0.20). There
      were no differences in the number of AF recurrences in the two groups (38 vs. 32,
      P = 0.66), but there were more instances of LA tachycardia (LAT) in the RF group
      than in the CB-Adv group (11 vs. 0, P < 0.01). LAT recurrence in RF patients was
      associated with RL creation (9 with vs. 2 without, P < 0.01). Among patients in
      whom a RL was created, arrhythmia-free survival was lower in the RF group than in
      the CB-Adv group (44.9% vs. 79.2%, P < 0.01). CONCLUSIONS: Arrhythmia recurrence
      rates in the two groups during midterm follow-up were comparable. RL creation
      during CB-Adv ablation resulted in acceptable outcomes.

PMID- 29227009
TI  - Fetal liver injury ameliorated by migration inhibitory factor inhibition in a rat
      model of acute pancreatitis in pregnancy.
AB  - AIM: This study was designed to investigate and assess fetal liver injury in a
      rat model of acute pancreatitis in pregnancy (APIP) as well as its possible
      mechanisms and potential therapeutic targets. METHODS: The APIP model was induced
      by sodium taurocholate in Sprague-Dawley rats during the third trimester. ISO-1,
      a macrophage migration inhibitory factor (MIF) antagonist, was given before the
      induction of APIP. In addition, sham-operated rats at later gestation were set as
      controls. Histological changes in the fetal liver and maternal pancreas were
      assessed. Amylase and lipase activity as well as the levels of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta were examined. The expression of
      MIF in fetal liver was determined by immunochemistry and the expression of NF
      kappaB, IkappaBalpha, high mobility group box-1 protein (HMGB1), TNF-alpha, and
      IL-1beta in fetal liver was determined by Western blot analysis. Ultrastructures
      of hepatic cells in fetal rats were observed under transmission electron
      microscopy. RESULTS: ISO-1 ameliorated the following: (i) pathological injuries
      in maternal pancreas and fetal liver; (ii) levels of TNF-alpha and IL-1beta in
      maternal serum; and (iii) levels of MIF, myeloperoxidase, NF-kappaB, HMGB1, TNF
      alpha, and IL-1beta in fetal liver. CONCLUSION: Pathological damage and an
      inflammatory response in fetal liver were induced by APIP, and MIF inhibition
      ameliorated fetal liver injury by inhibiting the inflammatory cascade.

PMID- 29227010
TI  - Prelabor screening for intrapartum fetal compromise in low-risk pregnancies at
      term: cerebroplacental ratio and placental growth factor.
AB  - OBJECTIVES: To determine the screening performance of low fetal cerebroplacental
      ratio (CPR), a marker of fetal adaptation to suboptimal growth, and maternal
      placental growth factor (PlGF) level, both in isolation and in combination, for
      the prediction of Cesarean section (CS) for intrapartum fetal compromise (IFC)
      and composite adverse neonatal outcome (CANO). METHODS: This was a prospective
      cohort study in low-risk women with uncomplicated singleton pregnancy from 36
      weeks' gestation to delivery. CPR and PlGF were assessed fortnightly and
      intrapartum and neonatal outcomes were recorded. CPR and PlGF values from the
      final assessment for each woman were corrected for gestational age and assessed
      for screening performance, firstly as continuous variables and then as binary
      predictors. RESULTS: Of the 264 women who consented to participate in the study,
      207 were included in the final analysis. Seven pregnancies required CS for IFC
      and 38 had CANO. Pregnancies delivered by CS for IFC had lower CPR and PlGF
      centiles than those in all other pregnancies. Pregnancies with CANO had a lower
      PlGF centile. The greatest areas under the receiver-operating characteristics
      curves (AUCs) for the prediction of CS for IFC (0.92; 95% CI, 0.86-0.97) and CANO
      (0.64; 95% CI, 0.54-0.74) were achieved by a combination of CPR 20th and PlGF
      33rd centile thresholds. This produced sensitivities, specificities and positive
      likelihood ratios for the prediction of CS for IFC of 100%, 86% and 7.14,
      respectively, and 34.2%, 87.0% and 2.63, respectively, for the prediction of
      CANO. There was no statistical difference in the AUC for CS for IFC between the
      combined model and when CPR was used alone, or for CANO between the combined
      model and CPR or PlGF in isolation. CONCLUSIONS: This pilot proof-of-concept
      study describes the screening performance of CPR and maternal PlGF level for CS
      for IFC in low-risk women from 36 weeks' gestation. It was found that CPR and
      maternal PlGF improved the overall predictive utility for CS for IFC, as well as
      that for CANO. However, given the lack of significant difference between the
      combined model and its individual components, it is debatable whether the
      combined model is a superior screening test. Copyright (c) 2017 ISUOG. Published
      by John Wiley & Sons Ltd.

PMID- 29227011
TI  - Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium
      falciparum growth by dual target inhibition.
AB  - Antimalarial drug resistance has emerged as a threat for treating malaria,
      generating a need to design and develop newer, more efficient antimalarial
      agents. This research aimed to identify novel leads as antimalarials. Dual
      receptor mechanism could be a good strategy to combat developing drug resistance.
      A series of benzimidazole acrylonitriles containing 18 compounds were designed,
      synthesized and evaluated for cytotoxicity, heme binding, ferriprotoporphyrin IX
      biomineralisation inhibition, and falcipain-2 enzyme assay. Furthermore, in
      silico docking and MD simulation studies were also performed.The tests revealed
      quite encouraging results. Three compounds, viz. R-01 (0.69 MUM), R-04 (1.60
      MUM), and R-08 (1.61 MUM), were found to have high antimalarial activity. These
      compounds were found to be in bearable cytotoxicity limits and their biological
      assay suggested that they had inhibitory activity against falcipain-2 and
      hemozoin formation. The docking revealed the binding mode of benzimidazole
      acrylonitrile derivatives and MD simulation studies revealed that the protein
      ligand complex was stable. The agents exhibit good hemozoin formation inhibition
      activity and, hence, may be utilized as leads to design a newer drug class to
      overcome the drug resistance of hemozoin formation inhibitors such as
      chloroquine.

PMID- 29227013
TI  - A new classification, treatment algorithm and prognosis-estimating system for
      ileosigmoid knotting.
AB  - Ileosigmoid knotting (ISK) is the wrapping of the ileum or sigmoid colon around
      the base of the other one, causing a double-loop intestinal obstruction. It
      requires urgent and effective resuscitation followed by emergency surgery, and
      its prognosis is poor [1,2]. Although ISK is a rare disease worldwide, with fewer
      than 500 cases reported in the literature to date [3,4], it is relatively common
      in Turkey [5,6]. This article is protected by copyright. All rights reserved.

PMID- 29227012
TI  - Superior anti-suicidal effects of electroconvulsive therapy in unipolar disorder
      and bipolar depression.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) has long been believed to reduce
      suicidal tendencies in patients with affective disorders; however, ECT
      recipients, who constitute the most severely ill and suicidal patients, are not
      eligible to participate in head-to-head randomized controlled trials. Large-scale
      studies are required to investigate the anti-suicidal effects of ECT vs
      psychopharmacotherapy. METHODS: A nationwide retrospective cohort study design
      was used. Data were obtained from the Taiwan National Health Insurance Research
      Database. Inpatients with unipolar disorder or bipolar disorder who received ECT
      (n = 487) were observed from 1 January 2000 to 31 December 2013 for suicide
      events. The non-ECT control cohort consisted of inpatients with
      psychopharmacotherapy randomly matched (ratio, 1:4) by age, sex, and diagnosis.
      RESULTS: After potential confounds had been accounted for, the adjusted hazard
      ratio (HR) was 0.803, indicating that ECT recipients showed a 19.7% lower risk of
      suicide than control individuals. The stratum-specific adjusted HR was 0.79 in
      patients with unipolar disorder (P = .041) and 0.923 in patients with bipolar
      disorder (P = .254). Upon further stratification of the patients with bipolar
      disorder by their affective states, the adjusted HR was 0.805 (P = .046) for
      bipolar depression, 1.048 for bipolar mania (P = .538), and 0.976 for mixed
      bipolar state (P = .126). CONCLUSIONS: Compared with psychopharmacotherapy, ECT
      exerted superior anti-suicidal effects in patients with unipolar disorder and
      bipolar depression; however, there was a lack of superior anti-suicidal effects
      of ECT in the treatment of patients with bipolar mania and mixed state.

PMID- 29227014
TI  - Comparison of weighted and composite scores for pre-clinical dental learners.
AB  - PURPOSE: The weighted mean (WM) method for combining scores of assessment
      components can provide outcomes with biased reliability and score precision. The
      objective of this study was to compare the traditional WM with another method
      utilising the composite score (CS) principle for combining scores of a final
      summative assessment exercise for a pre-clinical dental course. METHODS: Data
      were collected from the final examination of third-year Preclinical Operative and
      Esthetic Dentistry course consisting of 3 parts: practical competency, objective
      structured practical examination and a written examination with weights of 33%,
      17% and 50%, respectively. Scores from the 3 components were combined using the
      WM and CS methods. Weighted kappa was used to compare both approaches for
      agreement, and students' ranks were also compared. RESULTS: Combining scores
      using CS scheme produced lower scores overall compared to WM with more apparent
      effect for the male group. Agreement between WM and CS was moderate (kappa =
      0.44) with major differences between students' ranks across the 2 modalities as
      only 21% of the cohort retained their ranks. CONCLUSION: The CS method produced
      more reliable scores, resulting in moderate agreement with the WM and major shift
      in students' ranks. These findings necessitate further validity considerations
      before implementing the CS method and call for further studies that examine the
      consequences of composite measures in dental education.

PMID- 29227015
TI  - Indocyanine green fluorescence angiography (ICGFA) during laparoscopic and
      robotic colorectal surgery- a video vignette.
AB  - Anastomotic leaks are a dreaded complication of all colorectal surgery with the
      main factors contributing to it being tension on the anastomosis, intra-abdominal
      or systemic sepsis, distal obstruction, inadequate blood supply and improper
      surgical techniques. The leak rate of left-sided high colorectal resections can
      have a clinically significant leak rate from as low as 1-5% in high anterior
      resections to 7.9% in low anastomoses. This article is protected by copyright.
      All rights reserved.

PMID- 29227016
TI  - Patients with chronic bipolar disorder exhibit widespread increases in
      extracellular free water.
AB  - OBJECTIVES: Bipolar disorder (BP) is a debilitating psychiatric disease that is
      not well understood. Previous diffusion magnetic resonance imaging (dMRI) studies
      of BP patients found prominent microstructural white matter (WM) abnormalities of
      reduced fractional anisotropy (FA). Because FA is a nonspecific measure, relating
      these abnormalities to a specific pathology is difficult. Here, dMRI specificity
      was increased by free water (FW) imaging, which allows identification of changes
      in extracellular space (FW) from neuronal tissue (fractional anisotropy of tissue
      [FA-t]). Previous studies identified increased FW in early schizophrenia (SZ)
      stages which was replaced by widespread decreased FA-t in chronic stages. This is
      the first analysis utilizing this method to compare BP patients and controls.
      METHODS: 3 Tesla diffusion weighted imaging (3T DWI) data were acquired for 17
      chronic BP and 28 healthy control (HC) participants at Oxford University. Tract
      based spatial statistics was utilized to generate a WM skeleton. FW imaging
      deconstructed the diffusion signal into extracellular FW and tissue FA-t maps.
      These maps were projected onto the skeleton and FA, FA-t, and FW were compared
      between groups. RESULTS: We found significantly lower FA in BP patients when
      compared to HC in areas that overlapped with extensive FW increases. There were
      no FA-t differences. CONCLUSIONS: Our study suggests that chronic BP shows
      similar WM changes to early SZ, suggesting that extracellular FW increases could
      be a transient indication of recent psychotic episodes. Since FW increase in SZ
      has been suggested to be related to neuroinflammation, we theorize that
      neuroinflammation might be a shared pathology between chronic BP and early SZ.

PMID- 29227017
TI  - ortho-Directing Chromium Arene Complexes as Efficient Mediators for
      Enantiospecific C(sp2 )-C(sp3 ) Cross-Coupling Reactions.
AB  - A new strategy for the coupling of a broad scope of electronically diverse
      aromatics to boronic esters is reported. The coupling sequence, which relies on
      the directed ortho-lithiation of chromium arene complexes followed by boronate
      formation and oxidation, occurs with complete ortho-selectivity and
      enantiospecificity to give the coupling products in excellent yields and with
      high functional group tolerance. An intermediate chromium arene boronate complex
      was characterized by X-ray, NMR, and IR experiments to elucidate the reaction
      mechanism.

PMID- 29227018
TI  - A combination of dispersive liquid-liquid microextraction and surface plasmon
      resonance sensing of gold nanoparticles for the determination of ziram pesticide.
AB  - We have developed a reliable, fast, and highly sensitive analytical method
      utilizing dispersive liquid-liquid microextraction and gold nanoparticles probes
      for ziram (zinc bis(dimethyldithiocarbamate)) determination. The method is based
      on the in situ formation of gold nanoparticles in carbon tetrachloride as an
      organic phase. It was found that the trace levels of ziram influenced the
      formation of gold nanoparticles, leading to absorbance change of a sedimented
      phase. The results of the colorimetric ziram determination were in the
      concentration range of 0.12-2.52 ng/mL with a limit of detection of 0.06 ng/mL.
      The formation of the stable and dispersed gold nanoparticles in the organic phase
      provides a good precision for dispersive liquid-liquid microextraction method,
      resulting in the relative standard deviation of 3.8 and 1.2% for 0.56 and 1.58
      ng/mL of ziram, respectively. This method has been successfully used for the
      ziram determination in samples of well and river water, soil, potato, carrot,
      wheat, and paddy soil.

PMID- 29227019
TI  - Metal-Organic Framework-Derived Materials for Sodium Energy Storage.
AB  - Recently, sodium-ion batteries (SIBs) are extensively explored and are regarded
      as one of the most promising alternatives to lithium-ion batteries for
      electrochemical energy conversion and storage, owing to the abundant raw material
      resources, low cost, and similar electrochemical behavior of elemental sodium
      compared to lithium. Metal-organic frameworks (MOFs) have attracted enormous
      attention due to their high surface areas, tunable structures, and diverse
      applications in drug delivery, gas storage, and catalysis. Recently, there has
      been an escalating interest in exploiting MOF-derived materials as anodes for
      sodium energy storage due to their fast mass transport resulting from their
      highly porous structures and relatively simple preparation methods originating
      from in situ thermal treatment processes. In this Review, the recent progress of
      the sodium-ion storage performances of MOF-derived materials, including MOF
      derived porous carbons, metal oxides, metal oxide/carbon nanocomposites, and
      other materials (e.g., metal phosphides, metal sulfides, and metal selenides), as
      SIB anodes is systematically and completely presented and discussed. Moreover,
      the current challenges and perspectives of MOF-derived materials in
      electrochemical energy storage are discussed.

PMID- 29227020
TI  - Determination of herbicides in environmental water samples by simultaneous in
      syringe magnetic stirring-assisted dispersive liquid-liquid microextraction and
      silylation followed by GC-MS.
AB  - An on-line, fast, simple, selective, and sensitive method has been developed for
      the determination of three herbicides belonging to the following families:
      triazines (atrazine), chloroacetamide (alachlor), and phenoxy (2,4
      dichlorophenoxyacetic acid) in water samples. The method involves an in-syringe
      magnetic stirring-assisted dispersive liquid-liquid microextraction along with
      simultaneous silylation prior to their determination by gas chromatography with
      mass spectrometry. Extraction, derivatization, and preconcentration have been
      simultaneously performed using acetone as dispersive solvent, N-methyl-N-tert
      butyldimethylsilyltrifluoroacetamide as derivatization agent and
      trichloroethylene as extraction solvent. After stirring for 180 s, the sedimented
      phase was transferred to a rotary micro-volume injection valve (3 MUL) and
      introduced by an air stream into gas chromatograph with mass spectrometry
      detector. Recovery and enrichment factors were 87.2-111.2% and 7.4-10.4,
      respectively. Relative standard deviations were in the ranges of 6.6-7.4 for
      intraday and 9.2-9.6 for interday precision. The detection limits were in the
      range of 0.045-0.03 MUg/L, and good linearity was observed up to 200 MUg/L, with
      R2 ranging between 0.9905 and 0.9964. The developed method was satisfactorily
      applied to assess the occurrence of the studied herbicides in groundwater
      samples. The recovery test was also performed with values between 77 and 117%.

PMID- 29227021
TI  - Rapid characterization of the absorbed chemical constituents of Tangzhiqing
      formula following oral administration using UHPLC-Q-TOF-MS.
AB  - Tangzhiqing formula, a Chinese herbal formula, is used for the treatment of type
      II diabetes and prediabetes. Although its effectiveness has been certified by
      clinical use, its absorbed chemical constituents are not comprehensively
      represented. Thence, in order to reveal potential bioactive components and
      metabolism of Tangzhiqing formula, an ultra-high performance liquid
      chromatography with quadrupole time-of-flight mass spectrometry method was
      developed. A total of 86 absorbed components, including 38 prototype compounds
      and 48 metabolites, were identified in rat plasma, urine, and feces after oral
      administration of Tangzhiqing formula. This was the first systematic study on the
      chemical constituents and metabolic profiling of Tangzhiqing formula. The results
      indicated that alkaloids and flavonoids were main absorbed components, and
      glucuronidation and sulfation were the major metabolites. Moreover we concluded
      that alkaloids and flavonoids first underwent demethylation and hydrolysis
      reactions before biotransformed to phase II metabolites. This study provided
      valuable data for safety estimation of Tangzhiqing formula, which will be
      advantageous for clinical application.

PMID- 29227022
TI  - The GATA-type IVb zinc-finger transcription factor SsNsd1 regulates asexual
      sexual development and appressoria formation in Sclerotinia sclerotiorum.
AB  - The sclerotium, a multicellular structure composed of the compact aggregation of
      vegetative hyphae, is critical for the long-term survival and sexual reproduction
      of the plant-pathogenic fungus Sclerotinia sclerotiorum. The development and
      carpogenic germination of sclerotia are regulated by integrating signals from
      both environmental and endogenous processes. Here, we report the regulatory
      functions of the S. sclerotiorum GATA-type IVb zinc-finger transcription factor
      SsNsd1 in these processes. SsNsd1 is orthologous to the Aspergillus nidulans NsdD
      (never in sexual development) and the Neurospora crassa SUB-1 (submerged
      protoperithecia-1) proteins. Ssnsd1 gene transcript accumulation remains
      relatively low, but variable, during vegetative mycelial growth and multicellular
      development. Ssnsd1 deletion mutants (Deltansd1-KOs) produce phialides and
      phialospores (spermatia) excessively in vegetative hyphae and promiscuously
      within the interior medulla of sclerotia. In contrast, phialospore development
      occurs only on the sclerotium surface in the wild-type. Loss of SsNsd1 function
      affects sclerotium structural integrity and disrupts ascogonia formation during
      conditioning for carpogenic germination. As a consequence, apothecium development
      is abolished. The Ssnsd1 deletion mutants are also defective in the transition
      from hyphae to compound appressorium formation, resulting in a loss of
      pathogenicity on unwounded hosts. In sum, our results demonstrate that SsNsd1
      functions in a regulatory role similar to its ascomycete orthologues in
      regulating sexual and asexual development. Further, SsNsd1 appears to have
      evolved as a regulator of pre-penetration infectious development required for the
      successful infection of its many hosts.

PMID- 29227023
TI  - Sex-linked difference in blood oxygen saturation.
AB  - BACKGROUND: It is not known whether SpO2 in healthy volunteers is affected by
      sex. OBJECTIVE: To evaluate whether there are differences in SpO2 between young
      healthy adult males and females and to evaluate whether the differences are
      already present at birth. METHODS: We studied two cohorts of patients. The first
      one consisted of young adult volunteers (105 males and 102 females). In these
      patients, SpO2 was measured as well as selected anthropometric variables (height,
      weight), vital signs (respiratory rate, pulse rate and body temperature) and
      obtained data on menstrual cycle phase of the female participants. For the second
      cohort, we reanalyzed data from a previous prospective study that was performed
      to compare SpO2 of newborns infants born at different altitudes (sea level or 760
      m above sea level). MEASUREMENTS AND MAIN RESULTS: In young male adults, mean
      SpO2 was 97.1% +/- 1.2% versus 98.6% +/- 1.0% in females (P < .001). This
      difference remained significant (P = .002) after correction for BMI, BSA and age,
      variables that were significantly different between sexes in univariate analysis.
      The SpO2 in females was unaffected by menstrual phase. In contrast to findings in
      adults, there were no significant differences in SpO2 measurements in newborn
      infants attributable to sex. CONCLUSIONS: Healthy young female adults have a
      higher (1.5%) SpO2 than their male counterparts. This difference is not yet
      present at birth. Further studies are needed to determine the timing of sex
      differences, and to better define the mechanism(s) behind this observation.

PMID- 29227025
TI  - Light-Driven C-H Oxygenation of Methane into Methanol and Formic Acid by
      Molecular Oxygen Using a Perfluorinated Solvent.
AB  - The chlorine dioxide radical (ClO2. ) was found to act as an efficient oxidizing
      agent in the aerobic oxygenation of methane to methanol and formic acid under
      photoirradiation. Photochemical oxygenation of methane occurred in a two-phase
      system comprising perfluorohexane and water under ambient conditions (298 K, 1
      atm). The yields of methanol and formic acid were 14 and 85 %, respectively, with
      a methane conversion of 99 % without formation of the further oxygenated products
      such as CO2 and CO. Ethane was also photochemically converted into ethanol (19 %)
      and acetic acid (80 %). The methane oxygenation is initiated by the photochemical
      Cl-O bond cleavage of ClO2. to generate Cl. and O2 . The produced Cl. reacts with
      CH4 to form a methyl radical (CH3. ). Finally, the oxygenated products such as
      methanol and formic acid were given by the radical chain reaction. A fluorous
      solvent plays an important role of inhibiting the deactivation of reactive
      radical species such as Cl. and CH3. .

PMID- 29227024
TI  - Blood biomarkers as predictors of long-term mortality in COPD.
AB  - BACKGROUND: Blood biomarkers are easily accessible and might reflect chronic
      obstructive pulmonary disease (COPD) activity. AIM: The aim of this study was to
      determine whether a panel of blood biomarkers [C-reactive protein (CRP),
      neutrophils, eosinophils, albumin and vitamin D] could predict mortality in COPD.
      METHODS: We analyzed data from 431 COPD participants to the 2007-2010 National
      Health and Nutrition Examination Surveys who were followed for a median time of
      36 months. COPD was defined as post-bronchodilator forced expiratory volume in 1
      second (FEV1) and forced vital capacity ratio <0.70. Weibull survival analysis
      adjusted for covariates was performed to calculate the risk of mortality
      associated with the biomarkers, and C-statistics was used to assess their added
      predictive value. RESULTS: During follow-up, 38 of the 431 participants died.
      Participants with high CRP, eosinophil count <2%, hypoalbuminemia and
      hypovitaminosis D had worse baseline FEV1 and subsequently higher mortality
      compared to controls. In adjusted analysis, increasing CRP [hazard ratio (HR):
      4.45, 95% CI: 1.91-10.37] and neutrophil count (HR: 1.07, 95% CI: 1.03-1.11) as
      well as decreasing eosinophil count (HR: 7.03, 95% CI: 2.05-24.01) were
      associated with an increased risk of mortality. The addition of CRP with
      eosinophil and/or neutrophil count significantly improved a base model for the
      prediction of mortality which included age, gender, race/ethnicity, body mass
      index, smoking, poverty income ratio, asthma, diabetes, hypertension and history
      of stroke or myocardial infarction. CONCLUSION: High CRP and neutrophils as well
      as low eosinophils are predictive of poor COPD prognosis. They also add
      significant value to prediction models of mortality in COPD.

PMID- 29227026
TI  - The prevalence of asthma in Iranian adults: The first national survey and the
      most recent updates.
AB  - BACKGROUND: The worldwide increase in the prevalence of asthma has made it a
      major public-health concern. We aimed to identify the prevalence of asthma and
      asthma symptoms in adults living in urban and rural areas of Iran as a populated
      country with about 80 millions of residents. METHODS: This cross-sectional study
      was conducted to estimate the prevalence of asthma in adults between 20 and 44
      years old in all provinces of Iran. Data were collected by personal interview via
      a standardized questionnaire [European Community Respiratory Health Survey
      (ECRHS)] between November 2015 and February 2016. RESULTS: A total of 24 344
      individuals were enrolled. The prevalence of asthma was 8.9% [95% confidence
      interval (CI): 8.5-9.3]. The most common asthma symptoms were wheezing (14.2%, n
      = 3465), nocturnal cough (13.3%, n = 3234) and chest tightness (11.3%, n = 2760).
      Additionally, the prevalence of current asthma (taking asthma medications or
      asthma attack) was estimated to be 4.7% (n = 1155). Asthma was significantly more
      prevalent in males compared to females (P = .002), while no significant
      relationship was detected between gender and asthma after adjusted analysis with
      other variables. The prevalence of asthma was significantly higher in older
      participants (P < .001) and individuals with low educational level (P < .001).
      Interestingly, there was no significant relationship between asthma and area of
      residency (P = .8). CONCLUSIONS: The prevalence of asthma in Iran was similar to
      other Asian and European countries. However, repeated national surveys are
      required to determine the trend of asthma prevalence in Iran in comparison to
      other countries.

PMID- 29227027
TI  - Cryogenic modulation fast GC * GC-MS using a 10 m microbore column combination:
      Concept, method optimization, and application.
AB  - The present research is based on the concept of using a 10 m * 0.1 mm id column
      for cryogenic-modulation fast comprehensive two-dimensional gas chromatography
      with quadrupole mass spectrometry. Specifically, an 8.9 m * 0.1 mm id low
      polarity column was used as the first dimension, and a 1.1 m * 0.1 mm id medium
      polarity column was used as the second dimension. The main scope of the
      investigation was to develop a high peak-capacity method, with an analysis time
      of approximately 10 min. Various aspects related to method optimization are
      discussed, as well as separation parameters such as peak capacity (in each
      dimension, and as a total value), first-dimension sample capacity, peak widths,
      modulation ratio, sensitivity enhancement, and number of spectra per peak. The
      fast approach was evaluated in applications involving a mixture of cosmetic
      allergens and a sample of perfume. The approach proposed enables high-resolution
      separations in a short time (across the C8 -C23 alkane range), as well as a
      considerable reduction of the consumption of gases for modulation cooling and
      heating.

PMID- 29227028
TI  - Magnetic iron(III)-based framework composites for the magnetic solid-phase
      extraction of fungicides from environmental water samples.
AB  - We adopted a facile hydrofluoric acid-free hydro-/solvothermal method for the
      preparation of four magnetic iron(III)-based framework composites (MIL-101@Fe3 O4
      -COOH, MIL-101-NH2 @Fe3 O4 -COOH, MIL-53@Fe3 O4 -COOH, and MIL-53-NH2 @Fe3 O4 
      COOH). The obtained four magnetic iron(III)-based framework composites were
      applied to magnetic separation and enrichment of the fungicides (prochloraz,
      myclobutanil, tebuconazole, and iprodione) from environmental samples before high
      performance liquid chromatographic analysis. MIL-101-NH2 @Fe3 O4 -COOH showed
      more remarkable pre-concentration ability for the fungicides as compared to the
      other three magnetic iron(III)-based framework composites. The extraction
      parameters affecting enrichment efficiency including extraction time, sample pH,
      elution time, and the desorption solvent were investigated and optimized. Under
      the optimized conditions, the standard curve of correlation coefficients were all
      above 0.991, the limits of detection were 0.04-0.4 MUg/L, and the relative
      standard deviations were below 10.2%. The recoveries of two real water samples
      ranged from 71.1-99.1% at the low spiking level (30 MUg/L). Therefore, the MIL
      101-NH2 @Fe3 O4 -COOH composites are attractive for the rapid and efficient
      extraction of fungicides from environmental water samples.

PMID- 29227029
TI  - Differential requirement of BAK1 C-terminal tail in development and immunity.
AB  - BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) plays critical roles in plant
      developmental and immune signaling pathways. BAK1 and a large number of leucine
      rich repeat receptor-like kinases (LRR-RLKs) harbor a mysterious carboxyl
      terminal tail (CT) beyond their kinase domain. In this study we analyzed the
      biological significance of this CT region using a unique bak1 mutant allele which
      causes deletion of the CT region. We showed that BAK1 CT promotes its kinase
      activity and is required for pathogen-associated molecular pattern (PAMP)
      triggered immunity, but it is dispensable for brassinosteroid responses and
      BAK1/BKK1-inhibited cell death signaling. Therefore the BAK1 C-terminal tail is
      differentially required for its functions in development and immunity.

PMID- 29227030
TI  - Discrimination of FCGR2B polymorphism without coamplification of FCGR2A and
      FCGR2C genes.
AB  - The FCGR locus is characterized by high polymorphism and sequence homology. In
      particular, the Ile232Thr polymorphism in the FCGR2B gene results in inaccurate
      genotyping in most published papers. The purpose of the study was to develop an
      accurate genotyping assay able to discriminate this polymorphism.

PMID- 29227031
TI  - Innovative Sol-Gel Routes for the Bottom-Up Preparation of Heterogeneous
      Catalysts.
AB  - Heterogeneous catalysts can be prepared by different methods offering various
      levels of control on the final properties of the solid. In this account, we
      exemplify bottom-up preparation routes that are based on the sol-gel chemistry
      and allow to tailor some decisive properties of solid catalysts. First, an
      emulsion templating strategy is shown to lead to macrocellular self-standing
      monoliths with a macroscopic 3D structure. The latter can be used as catalyst or
      catalyst supports in flow chemistry, without requiring any subsequent shaping
      step. Second, the aerosol-assisted sol-gel process allows for the one-step and
      continuous production of porous mixed oxides. Tailored textural properties can be
      obtained together with an excellent control on composition and homogeneity.
      Third, the application of non-hydrolytic sol-gel routes, in the absence of water,
      leads to mixed oxides with outstanding textural properties and with peculiar
      surface chemistry. In all cases, the resulting catalytic performance can be
      correlated with the specificities of the preparation routes presented. This is
      exemplified in catalytic reactions in the fields of biomass conversion, petro
      chemistry, enantioselective organic synthesis, and air pollution mitigation.

PMID- 29227032
TI  - Efficacy and safety of low-dose urokinase for the treatment of hemodynamically
      stable AECOPD patients with acute pulmonary thromboembolism.
AB  - PURPOSE: The aim of this study was to assess the incidence of pulmonary
      thromboembolism (PTE) in patients with acute exacerbation of chronic obstructive
      pulmonary disease (AECOPD),and to evaluate the efficacy and safety of low-dose
      urokinase (UK) thrombolysis therapy when treating hemodynamically stable AECOPD
      patients with acute PTE (AECOPD-PTE). METHODS: A total of 419 AECOPD patients,
      including 96 AECOPD-PTE, were enrolled. A total of 30 AECOPD-PTE patients were
      collected retrospectively, and 66 AECOPD-PTE patients were prospectively divided
      into anticoagulation-only, low-dose UK and standard-dose UK groups. Follow-up 1
      year, we evaluated the efficacy and safety of low-dose UK therapy for
      hemodynamically stable AECOPD-PTE patients. RESULTS: The incidence of PTE in
      AECOPD patients was 22.9% (96/419), which increased with COPD severity degree
      ranging from 3.5% (2/57) in mild, 13.6% (19/140) in moderate and 33.8% (75/222)
      in severe subgroups (P < .05). In the prospective study, the total effective rate
      of low-dose UK group 97.2% (35/36) was higher than that in anticoagulation 75.0%
      (12/16) and standard-dose UK group 78.6% (11/14) respectively (P < .05). In the
      follow-up, the adverse events rate in low-dose UK group 8.3% (3/36) was
      significantly lower than that in anticoagulation group 25.0% (4/16) and standard
      dose UK group 71.4% (10/14) respectively (P < .05). In addition, the mean PTE
      recurrence time of low-dose UK group (9.0 +/- 0) months was longer than
      anticoagulation group (2.0 +/- 1.41) months (P < .05). AECOPD relapse time in
      anticoagulation, low-dose UK and standard-dose UK groups corresponding to (8.5 +/
      2.12), (9.0 +/- 0) and (8.8 +/- 3.40) months were compared with no significant
      difference (P > .05). CONCLUSIONS: The incidence of PTE in AECOPD patients was
      22.9%, especially with higher occurrence rate in severe COPD. Compared with
      anticoagulation-only therapy, low-dose UK treatment (500 000 IU/day for 5-7 days)
      could obtain a better efficacy and safety in hemodynamically stable AECOPD
      patients with acute PTE, corresponding with a higher effective rate (97.2%) and
      lower adverse events rate (8.3%) respectively.

PMID- 29227033
TI  - Autopsy findings in EPG5-related Vici syndrome with antenatal onset: Additional
      report of Focal cortical microdysgenesis in a second trimester fetus.

PMID- 29227034
TI  - The clinical course of late-life bipolar disorder, looking back and forward.
AB  - OBJECTIVES: Little is known about the course of late-life bipolar disorder
      (LLBD). First, we studied patients with LLBD retrospectively with regard to age
      at first mood episode, onset polarity, predominant polarity and episode density
      and its associations with other clinical variables. Next, we examined
      prospectively the clinical course and its associated factors. METHODS: Data were
      used from a dynamic cohort (Dutch Older Bipolars [DOBi]) including 101 patients
      with LLBD (mean age of 68.9 years) at baseline in 2012, with 3-year follow-up
      measurements available for 64 of these patients. Retrospective course was
      assessed by diagnostic interviews, and at follow-up polarity and duration for
      each consecutive episode were noted. Linear and logistic analyses were performed
      to assess associations between relevant factors and outcome. RESULTS: The mean
      age at the first episode was 33.0 years. Onset polarity was depression in 44.6%
      of patients, with a predominant polarity of depression in 47.5%. At 3-year follow
      up, 37.5% of patients reported at least one mood episode, mainly depression. Life
      events, somatic illness, use of lithium and other factors were not associated
      with recurrence during the 3-year follow-up. DISCUSSION: A relapse rate of 37.5%
      in 3 years is high, considering that LLBD patients generally have a longer
      history of disease and were receiving care and medication. The course of LLBD can
      provide important information on which clinical factors are associated with
      recurrence. Further phenotyping may reveal unique predictors for outcome, and
      both course specifiers and clinical variables should be included.

PMID- 29227035
TI  - Mass Spectrometry Analyses of Multicellular Tumor Spheroids.
AB  - Multicellular tumor spheroids (MCTS) are a powerful biological in vitro model,
      which closely mimics the 3D structure of primary avascularized tumors. Mass
      spectrometry (MS) has established itself as a powerful analytical tool, not only
      to better understand and describe the complex structure of MCTS, but also to
      monitor their response to cancer therapeutics. The first part of this review
      focuses on traditional mass spectrometry approaches with an emphasis on
      elucidating the molecular characteristics of these structures. Then the mass
      spectrometry imaging (MSI) approaches used to obtain spatially defined
      information from MCTS is described. Finally the analysis of primary spheroids,
      such as those present in ovarian cancer, and the great potential that mass
      spectrometry analysis of these structures has for improved understanding of
      cancer progression and for personalized in vitro therapeutic testing is
      discussed.

PMID- 29227036
TI  - Bottom-up Nanoencapsulation from Single Cells to Tunable and Scalable Cellular
      Spheroids for Hair Follicle Regeneration.
AB  - Cell surface engineering technology advances cell therapeutics and tissue
      engineering by accurate micro/nanoscale control in cell-biomaterial ensembles and
      cell spheroids formation. By tailoring cell surface, microgels can encapsulate
      cells for versatile uses. However, microgels are coated in a thick layer to house
      multiple cells together but not a single cell based. Besides, excessive
      deposition on cell surface is detrimental to cellular functions. Herein, layer-by
      layer (LbL) self-assembly to encapsulate single cell using nanogel is reported,
      owing to its security and tunable thickness at nanoscale, and further forms cell
      spheroids by physical cross-linking on nanogel-coated cells for delivery. A hair
      follicle (HF) regeneration model where the dermal papilla cells (DPCs) are given
      a 3D installation to maintain its ability of HF induction during in vitro culture
      is studied. Dermal papilla (DP) spheroids are optimized and that LbL-DPCs
      aggregation is akin to primary DP is demonstrated. The markers ALP, Versican, and
      NCAM are examined to investigate that high-passaged (P8) DP spheroids can restore
      the hair induction potential, which are lost in 2D culture. New HFs are
      regenerated successfully by implantation of DP spheroids in vivo.

PMID- 29227037
TI  - Prospective transfrontal sheep model of skull-base reconstruction using
      vascularized mucosa.
AB  - BACKGROUND: No high-fidelity animal model exists to examine prospective wound
      healing following vascularized reconstruction of the skull base. Such a model
      would require the ability to study the prospective behavior of vascularized
      mucosal repairs of large dural and arachnoid defects within the intranasal
      environment. The objective of this study was to therefore develop and validate a
      novel, in vivo, transfrontal sheep model of cranial base repair using
      vascularized sinonasal mucosa. METHODS: Twelve transfrontal craniotomy and 1.5-cm
      durotomy reconstructions were performed in 60-kg to 70-kg Dorset/Ovis Aries sheep
      using vascularized mucosa with or without an adjunctive BiodesignTM underlay
      graft (n = 6 per group). Histologic outcomes were graded (scale, 0 to 4) by a
      blinded veterinary histopathologist after 7, 14, and 28 days for a range of wound
      healing parameters. RESULTS: All sheep tolerated the surgery, which required 148
      +/- 33 minutes. By day 7, the mucosa was fully adherent with complete
      partitioning of the sinus and intracranial compartments. Fibroblast infiltration
      and flap neovascularization scores significantly increased between day 7 (0.3 +/-
      0.5 and 0.0 +/- 0.0) and day 28 (4.0 +/- 0.0, p = 0.01 and 2.0 +/- 0.8, p = 0.01;
      respectively), while hemorrhage scores significantly decreased from 2.5 +/- 0.6
      to 0.0 +/- 0.0 (p = 0.01). The inflammatory scores were not significantly
      different between the heterologous graft and control sides. CONCLUSION: The
      described sheep model accurately reflects prospective intranasal wound healing
      following vascularized mucosal reconstruction of dural defects. This model can be
      used in future studies to examine novel reconstructive materials, tissue glues,
      and transmucosal drug delivery to the central nervous system.

PMID- 29227038
TI  - Molecular Design of Efficient Organic D-A-pi -A Dye Featuring Triphenylamine as
      Donor Fragment for Application in Dye-Sensitized Solar Cells.
AB  - A metal-free organic sensitizer, suitable for the application in dye-sensitized
      solar cells (DSSCs), has been designed, synthesized and characterized both
      experimentally and theoretically. The structure of the novel donor-acceptor-pi
      bridge-acceptor (D-A-pi-A) dye incorporates a triphenylamine (TPA) segment and 4
      (benzo[c][1,2,5]thiadiazol-4-ylethynyl)benzoic acid (BTEBA). The triphenylamine
      unit is widely used as an electron donor for photosensitizers, owing to its
      nonplanar molecular configuration and excellent electron-donating capability,
      whereas 4-(benzo[c][1,2,5]thiadiazol-4-ylethynyl)benzoic acid is used as an
      electron acceptor unit. The influences of I3- /I- , [Co(bpy)3 ]3+/2+ and
      [Cu(tmby)2 ]2+/+ (tmby=4,4',6,6'-tetramethyl-2,2'-bipyridine) as redox
      electrolytes on the DSSC device performance were also investigated. The maximal
      monochromatic incident photon-to-current conversion efficiency (IPCE) reached 81
      % and the solar light to electrical energy conversion efficiency of devices with
      [Cu(tmby)2 ]2+/+ reached 7.15 %. The devices with [Co(bpy)3 ]3+/2+ and I3- /I-
      electrolytes gave efficiencies of 5.22 % and 6.14 %, respectively. The lowest
      device performance with a [Co(bpy)3 ]3+/2+ -based electrolyte is attributed to
      increased charge recombination.

PMID- 29227039
TI  - Mid-term results of bariatric surgery in morbidly obese Japanese patients with
      slow progressive autoimmune diabetes.
AB  - INTRODUCTION: Bariatric surgery is recognized as an effective treatment for type
      2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus,
      especially slowly progressive insulin-dependent diabetes mellitus, are limited.
      METHODS: We investigated five Japanese patients with slowly progressive insulin
      dependent diabetes mellitus who underwent bariatric surgery at our center.
      RESULTS: Five morbidly obese glutamic acid decarboxylase antibody-positive
      diabetic patients underwent two different types of bariatric surgery. The mean
      titer of anti-glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean
      preoperative bodyweight and BMI were 113 kg and 39.6 kg/m2 , respectively. The
      mean hemoglobin A1c was 8.4%. The mean fasting serum C-peptide was 5.0 ng/mL.
      Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic
      sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At
      one year after surgery, the mean bodyweight and BMI significantly dropped, and
      the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was
      5.7%. This favorable trend was maintained at mid-term. CONCLUSION: Bariatric
      surgery for morbidly obese patients with anti-glutamic acid decarboxylase
      antibody-positive type 1 diabetes mellitus, especially slow progressive
      autoimmune diabetes, seemed effective in achieving mid-term glycemic control.
      Longer follow-up with a larger number of patients, as well as validation with
      more advanced patients with slowly progressive insulin-dependent diabetes
      mellitus, will be needed.

PMID- 29227040
TI  - Towards Sustainable H2 Production: Rational Design of Hydrophobic Triphenylamine
      based Dyes for Sensitized Ethanol Photoreforming.
AB  - Donor-acceptor dyes are a well-established class of photosensitizers, used to
      enhance visible-light harvesting in solar cells and in direct photocatalytic
      reactions, such as H2 production by photoreforming of sacrificial electron donors
      (SEDs). Amines-typically triethanolamine (TEOA)-are commonly employed as SEDs in
      such reactions. Dye-sensitized photoreforming of more sustainable, biomass
      derived alcohols, on the other hand, was only recently reported by using methanol
      as the electron donor. In this work, several rationally designed donor-acceptor
      dyes were used as sensitizers in H2 photocatalytic production, comparing the
      efficiency of TEOA and EtOH as SEDs. In particular, the effect of hydrophobic
      chains in the spacer and/or the donor unit of the dyes was systematically
      studied. The H2 production rates were higher when TEOA was used as SED, whereas
      the activity trends depended on the SED used. The best performance was obtained
      with TEOA by using a sensitizer with just one bulky hydrophobic moiety,
      propylenedioxythiophene, placed on the spacer unit. In the case of EtOH, the best
      performing sensitizers were the ones featuring a thiazolo[5,4-d]thiazole internal
      unit, needed for enhancing light harvesting, and carrying alkyl chains on both
      the donor part and the spacer unit. The results are discussed in terms of
      reaction mechanism, interaction with the SED, and structural/electrochemical
      properties of the sensitizers.

PMID- 29227041
TI  - A 14-Protein Signature for Rapid Identification of Poor Prognosis Stage III
      Metastatic Melanoma.
AB  - PURPOSE: To validate differences in protein levels between good and poor
      prognosis American Joint Committee on Cancer (AJCC) stage III melanoma patients
      and compile a protein panel to stratify patient risk. EXPERIMENTAL DESIGN:
      Protein extracts from melanoma metastases within lymph nodes in patients with
      stage III disease with good (n = 16, >4 years survival) and poor survival (n =
      14, <2 years survival) were analyzed by selected reaction monitoring (SRM).
      Diagonal Linear Discriminant Analysis (DLDA) was performed to generate a protein
      biomarker panel. RESULTS: SRM analysis identified ten proteins that were
      differentially abundant between good and poor prognosis stage III melanoma
      patients. The ten differential proteins were combined with 22 proteins identified
      in our previous work. A panel of 14 proteins was selected by DLDA that was able
      to accurately classify patients into prognostic groups based on levels of these
      proteins. CONCLUSIONS AND CLINICAL RELEVANCE: The ten differential proteins
      identified by SRM have biological significance in cancer progression. The final
      signature of 14 proteins identified by SRM could be used to identify AJCC stage
      III melanoma patients likely to have poor outcomes who may benefit from adjuvant
      systemic therapy.

PMID- 29227042
TI  - Ex vivo confocal microscopy features of cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Rapid microscopic evaluation of cutaneous squamous cell carcinoma
      (SCC), its grade of differentiation and level of invasiveness would enable better
      management of patients' therapy. OBJECTIVES: Analyzing specific ex vivo confocal
      microscopy criteria whether they can predict diagnosis of invasive SCC vs
      carcinoma in situ and poorly differentiated or undifferentiated vs well and
      moderately differentiated SCC. METHODS: Ex vivo confocal images of 102 SCCs in 57
      patients were evaluated immediately after excision for the presence of predefined
      criteria based on confocal and histological knowledge. RESULTS: In
      histopathological examination, 30 SCCs were in situ and 72 invasive. Of these, 29
      invasive SCC tumors were well, 19 moderately, 15 poorly differentiated and 9
      undifferentiated. chi2 analysis demonstrated that presence of erosion/ulceration,
      plump bright or speckled cells in dermis, keratin pearls and peritumoral
      inflammatory infiltrate correlated with diagnosis of invasive SCC.
      Erosion/ulceration and peritumoral inflammatory infiltrate were observed more
      frequently in poorly differentiated or undifferentiated tumors. Plump bright or
      speckled cells in the dermis were observed less often in well-differentiated
      tumors. The presence of keratin pearls was associated with well or moderately
      differentiated tumors. CONCLUSION: Ex vivo CLSM allowed rapid examination of SCC
      and provided useful information on invasiveness and grading of the tumor.

PMID- 29227043
TI  - The association of air pollutants and allergic and nonallergic rhinitis in
      chronic rhinosinusitis.
AB  - BACKGROUND: There has been little investigation regarding air quality and
      rhinitis in the pathophysiology of upper airway disease. In this study, we
      assessed the impact of inhalant pollutants (particulate matter 2.5 [PM2.5 ] and
      black carbon [BC]) on allergic rhinitis and chronic rhinosinusitis (CRS) disease
      severity. METHODS: CRS patients with nasal polyps (CRSwNP) and without polyps
      (CRSsNP) were identified. Spatial modeling from pollutant monitoring sites was
      used to estimate exposures for patients meeting the inclusion criteria (total, n
      = 125; CRSsNP, n = 67; CRSsNP, n = 58). Skin-prick, intradermal dilutional, and
      in-vitro testing methods were utilized to determine aeroallergen sensitization.
      Disease severity indicators were measured by modified Lund-Mackay score (LMS),
      the 22-item Sino-Nasal Outcome Test (SNOT-22), systemic steroid therapy, and
      number of functional endoscopic sinus surgeries (FESS). RESULTS: Thirty-six
      percent (n = 45) of patients who described rhinitis symptoms demonstrated no
      reactivity to aeroallergen testing. Sixty-four percent (n = 80) tested positive
      for at least 1 allergen, with no differences found between CRSsNP and CRSwNP
      (62.1% vs 67.2%). There were significant differences in air pollutants between
      patients testing negative and positive for allergies (nonallergic vs allergic:
      PM2.5 , 11.32 vs 11.07 MUg/m3 , p = 0.030; BC, 0.81 vs 0.76 absorbance, p
      =0.044). Nonallergic CRSwNP demonstrated higher PM2.5 compared with allergic
      counterparts (11.48 vs 11.09 MUg/m3 , p = 0.032). A similar pattern was observed
      with BC (0.82 vs 0.75 absorbance, p = 0.017). In CRSsNP, BC correlated
      significantly with SNOT-22 (r = 0.55, p = 0.042). CONCLUSION: Our results suggest
      that small inhalant pollutants may contribute to nonallergic symptomatology in
      patients with and without nasal polyps. Regardless of allergy status, BC may play
      a role in CRS symptom severity.

PMID- 29227044
TI  - Utility of core biopsy with concurrent ROSE FNA in the diagnosis of pancreatic
      tumor-does the biopsy add any diagnostic benefit?
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and
      endoscopic ultrasound-guided core-needle biopsy (EUS-CNB) are widely used for
      diagnosis of pancreatic tumors. The aim of our study was to compare the
      diagnostic performance of ROSE EUS-FNA and EUS-CNB for diagnosis of pancreatic
      malignancy during the same EUS. METHODS: Patients who underwent both FNA and CNB
      during the same EUS for pancreatic solid lesion were reviewed retrospectively.
      Sample adequacy, diagnostic yield (defined as percentage of definitive
      diagnosis), sensitivity and specificity for malignancy were compared between FNA
      and CNB. RESULTS: A total of 48 patients with solid pancreatic lesions were
      evaluated. The proportions of adequate samples were 48/48 (100%) for FNA and
      45/48 (93.7%) for core biopsy (P = .24). The diagnostic yield was 42/48 (87.5%)
      and 33/48 (68.7%) for FNA and CNB respectively (P = .046). The incremental
      increase in diagnostic yield by combining both methods was 2/48 (4%). The
      diagnostic yield for malignancy was 30/32 (93.7%) for FNA and 23/32 (71.8%) for
      CNB (P = .043). The sensitivity for the diagnosis of malignancy for FNA and CNB
      were 90.6% and 69%, respectively (P = .045). The specificity was 100% for both
      methods. The sensitivity for diagnosing malignancy increased to 93.8% when the
      two methods were combined. The difference in diagnostic yield was not associated
      with lesion size or location. CONCLUSION: EUS-guided FNA is a superior method of
      assessing solid pancreatic lesion and pancreatic malignancy with better
      diagnostic yield and higher sensitivity than EUS-CNB.

PMID- 29227045
TI  - Detection of depth-depend changes in porcine cartilage after wear test using
      Raman spectroscopy.
AB  - Cartilage damage and wear can lead to severe diseases, such as osteoarthritis,
      thus, many studies on the cartilage wear process have already been performed to
      better understand the cartilage wear mechanism. However, most characterization
      methods focus on the cartilage surface or the total wear extent. With the
      advantages of high spatial resolution and easy characterization, Raman
      microspectroscopy was employed for the first time to characterize full-depth
      changes in the cartilage extracellular matrix (ECM) after wear test. Sections
      from the cartilage samples after wear were compared with sections from the
      control group. Univariate and multivariate analyses both indicated that collagen
      content loss at certain depths (20%-30% relative to the cartilage surface) is
      possibly the dominating alteration during wear rather than changes in collagen
      fiber orientation or proteoglycan content. These findings are consistent with the
      observations obtained by scanning electron microscopy and histological staining.
      This study successfully used Raman microspectroscopy efficiently assess full
      depth changes in cartilage ECM after wear test, thus providing new insight into
      cartilage damage and wear.

PMID- 29227046
TI  - Prevalence of comorbidities in patients with obstructive sleep apnea syndrome,
      overlap syndrome and obesity hypoventilation syndrome.
AB  - INTRODUCTION: Sleep-disordered breathing causes a burden to the sufferer, the
      health care system and the society. Most studies have focused on obstructive
      sleep apnea (OSA); however, the prevalence of comorbidities in patients affected
      by overlap syndrome (OS) and obesity hypoventilation syndrome (OHS) has not been
      carefully evaluated. STUDY OBJECTIVES: The principal aim of this study was to
      identify the presence of comorbidities in patients suffering from OSA, OS, OHS
      and the differences in three groups of patients. Another purpose was to verify if
      sleepiness is associated with a greater prevalence of comorbidities. METHODS: A
      retrospective analysis in 989 adults referred for sleep diagnostic testing to our
      sleep center was performed. Patients were classified in OSA (721), OS (123) and
      OHS (145). RESULTS: The prevalence of comorbidities was higher in patients
      affected by OS and was the highest in the OHS group, while the prevalence of
      arterial hypertension is the highest in patients affected by OS. The probability
      of having more than two comorbidities follows the same trend. Excessive daytime
      sleepiness was associated with an increased rate of arterial hypertension,
      diabetes mellitus and the presence of multimorbidity in each group of patients.
      CONCLUSIONS: The presence and the association of comorbidities seem to be higher
      in patients suffering from OSA, OS and OHS. Subjects suffering of OHS present a
      high prevalence of main diseases despite their younger age compared with others
      patients with SDB. Sleepiness may have a role, at least in a subset of these
      patients, into the development of comorbidities.

PMID- 29227048
TI  - The prevalence of Eustachian tube dysfunction symptoms in patients with chronic
      rhinosinusitis.
AB  - BACKGROUND: While Eustachian tube dysfunction (ETD) is a known comorbidity of
      chronic rhinosinusitis (CRS), the prevalence of ETD symptoms in the CRS
      population is poorly understood. We sought to determine the cross-sectional
      prevalence of ETD in patients with CRS using the validated Eustachian Tube
      Dysfunction Questionnaire (ETDQ-7) and to correlate ETDQ-7 scores with 22-item
      Sino-Nasal Outcome Test (SNOT-22) scores, endoscopy scores, and computed
      tomography (CT) scores. METHODS: A total of 101 patients with confirmed CRS
      completed the ETDQ-7 and SNOT-22 at their initial visit to our rhinology clinic.
      Lund-Mackay CT and Lund-Kennedy endoscopy scores were also obtained. Spearman's
      correlation coefficient (rho) was calculated. RESULTS: Among the 101 patients, 49
      patients (48.5%) had an ETDQ-7 score of >=14.5, signifying clinically significant
      ETD. The mean +/- standard deviation (SD) ETDQ-7 score of the entire cohort was
      17.8 +/- 10.1. There was a moderately strong correlation between ETDQ-7 and the
      SNOT-22 ear subdomain (rho = 0.691, p < 0.001). The correlation coefficient
      between ETDQ-7 and total SNOT-22 scores was rho = 0.491 (p < 0.001), indicating
      moderate correlation. ETDQ-7 scores were poorly correlated to objective measures
      of sinonasal disease, including Lund-Mackay CT score (rho = -0.055, p = 0.594)
      and Lund-Kennedy endoscopy score (rho = -0.099, p = 0.334). CONCLUSION: Symptoms
      of ETD are highly prevalent among patients with CRS as documented by patient
      reported outcome measures. The correlation between ETDQ-7 scores and SNOT-22 ear
      subdomain scores is moderately strong, while the correlation between ETDQ-7
      scores and SNOT-22 scores is moderate. ETD severity does not correlate with CT
      score or nasal endoscopy score.

PMID- 29227049
TI  - Rib fracture fixation in a South African public trauma service.
AB  - BACKGROUND: Rib fractures and flail chests have traditionally been treated
      nonoperatively. Current literature suggests that it is not only safe and feasible
      but also desirable to perform fixation of severe rib fractures. Our unit in the
      Pietermaritzburg public sector adopted rib fracture fixation in 2014 and in this
      audit we assess its feasibility in our setting. METHODS AND RESULTS: We audited
      our first nine cases of rib fracture fixation performed to date, of which seven
      were males. The age range was 29 to 67 years. All patients had multiple rib
      fractures with severe displacement; one had bilateral flail segments and one had
      severely displaced unilateral single fractures without flail; all others had
      unilateral flail chests. Time from injury to operation ranged from 3 to 20 days.
      Of six ventilator dependent patients, all but one were liberated from the
      ventilator within 3 days after fixation (1-3 days). The remaining patient
      remained ventilator dependent for 10 days while recovering from traumatic brain
      injury. This patient aside, all were discharged from ICU within 5 days. Patients
      with no other significant injuries were discharged from hospital within five to
      eight days; all being mobile within five days. Procedure-related complications
      included accidental pleural breach during rib mobilization necessitating
      intercostal drain placement (2 patients) and superficial wound infection (1
      patient). All patients were discharged well. CONCLUSION: Rib fracture fixation is
      safe and feasible in our unit and is feasible in the South African public sector.

PMID- 29227050
TI  - Barriers to accessing ATLS provider course for junior doctors at a major
      university hospital in South Africa.
AB  - BACKGROUND: Advanced trauma life support (ATLS) is the international standard of
      care and forms the basis of trauma training in South Africa. Previous local
      studies demonstrated a low completion rate among junior doctors (JD). This study
      was designed to determine the reasons and identify possible barriers of JDs to
      accessing the ATLS course at a major university hospital. METHOD: This was a
      prospective study utilising a structured survey that included all JDs who were
      undertaking their internship training. RESULTS: A total of 105 JDs completed the
      survey. Sixty-two percent were female (65/105) and the mean age was 25 years.
      Forty-eight percent (50/105) of all JDs were post graduate year 1 (PGY 1) and the
      remaining 52% were post graduate year 2 (PGY 2) JDs. Sixty-two percent (65/105)
      of all respondents had completed their mandatory rotation in surgery. The reasons
      for non-attendance of ATLS were: unable to secure a place on course (52%), unable
      to afford course fee (18%), permission for attendance not granted (14%), unable
      to obtain study leave (10%) and lack of interest (5%). Subgroup analysis
      comparing the reasons for PGY1s vs PGY2s demonstrated that not being able to
      secure a place on course was more common among PGY2s [19% vs 33%, p < 0.001]
      while financial reasons were more common among PGY1s [18% vs 0%, p < 0.001].
      CONCLUSION: The primary barriers for JDs to attending ATLS training is difficulty
      in accessing the course due to oversubscription, financial reasons, followed by
      difficulty in obtaining professional development leave due to staff shortage.
      There is an urgent need to improve access to the ATLS training course for JDs in
      our environment.

PMID- 29227047
TI  - Advances in Stimulus-Responsive Polymeric Materials for Systemic Delivery of
      Nucleic Acids.
AB  - Polymeric materials that respond to a variety of endogenous and external stimuli
      are actively developed to overcome the main barriers to successful systemic
      delivery of therapeutic nucleic acids. Here, an overview of viable stimuli that
      are proved to improve systemic delivery of nucleic acids is provided. The main
      focus is placed on nucleic acid delivery systems (NADS) based on polymers that
      respond to pathological or physiological changes in pH, redox state, enzyme
      levels, hypoxia, and reactive oxygen species levels. Additional discussion is
      focused on NADS suitable for applications that use external stimuli, such as
      light, ultrasound, and local hyperthermia.

PMID- 29227051
TI  - Serum alcohol levels correlate with injury severity and resource utilization.
AB  - BACKGROUND: Alcohol consumption leads to violence and poor judgement. The
      resultant trauma is the leading cause of emergency department visits. In South
      Africa, alcohol-related emergency visits can be as high as 57%. The purpose of
      this prospective study was to establish the prevalence of positive blood alcohol
      and Blood Alcohol Concentration (BAC) at a tertiary trauma unit in Durban, and to
      correlate it with injury severity, length of hospital stay and resource
      utilization. METHOD: A total of 100 patients from King Edward trauma unit were
      analysed prospectively during the period December 2014 to February 2015. The BAC
      was correlated with Injury Severity Score (ISS), mechanism of injury, length of
      stay, and in-hospital mortality. Pearson chi-square test, Wilcoxon rank sum and
      student t-test were used for statistical analysis. RESULTS: Eighty-eight patients
      were male. The mean age was 30 +/- 9.3 years. Forty-seven patients tested
      positive for blood alcohol, of whom 81% were above the legal limit for
      professional drivers. The mean BAC among the alcohol positive patients was 0.146
      g/dL. Positive blood alcohol was associated with significantly higher ISS scores
      (p = 0.0004). Injuries due to interpersonal violence were seen in 83 patients of
      whom 42 (51%) had positive blood alcohol. Hospital stay for alcohol positive
      patients was significantly longer compared to alcohol negative patients (p <
      0.001). CONCLUSION: The prevalence of blood alcohol in the trauma population is
      high. Positive blood alcohol is associated with high ISS and longer hospital
      stays.

PMID- 29227052
TI  - Laparoscopy or clinical follow-up to detect occult diaphragm injuries following
      left-sided thoracoabdominal stab wounds: A pilot randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to determine whether patients with left
      sided thoracoabdominal (TA) stab wounds can be safely treated with clinical and
      chest X-ray follow up. METHOD: A prospective, randomized control study was
      conducted at Groote Schuur Hospital from September 2009 through to November 2014.
      Patients with asymptomatic left TA stab wounds included in the trial were
      randomized into two groups. Group A underwent diagnostic laparoscopy and Group B
      underwent clinical and radiological follow-up. RESULTS: Twenty-seven patients
      were randomized to Group A (N=27) and thirty-one to Group B (N=31). All patients
      were young males with a median age of 26 years (range 18 to 48). The incidence of
      occult diaphragm injury in Group A was 29%. All diaphragm injuries found at
      laparoscopy were repaired. The mean hospital stay for the patients in Group A was
      5 days (SD 1.3), compared to a mean hospital stay of 2.9 days (SD, 1.5), in Group
      B (p < 0.001). All patients in Group B had normal chest X-rays at their last
      visit. The mean follow-up time was 24 months (median: 24; interquartile range: 1
      40). There was no morbidity or mortality in Group B. CONCLUSION: Clinical and
      radiological follow-up are feasible and appear to be safe, in the short term, in
      patients who harbour occult diaphragm injuries after left TA stab wounds. Until
      studies showing the natural history of diaphragm injury in humans are available,
      laparoscopy should remain the gold standard in treatment.

PMID- 29227053
TI  - Quantifying the funding gap for management of traumatic brain injury at a major
      trauma centre in South Africa.
AB  - BACKGROUND: Trauma is an eminently preventable disease. However, prevention
      programs divert resources away from other priorities. Costing trauma related
      diseases helps policy makers to make decisions on re-source allocation. We used
      data from a prospective digital trauma registry to cost Traumatic Brain Injury
      (TBI) at our institution over a two-year period and to estimate the funding gap
      that exists in the care of TBI. METHOD: All patients who were admitted to the
      Pietermaritzburg Metropolitan Trauma Service (PMTS) with TBI were identified from
      the Hybrid Electronic Medical Registry (HMER). A micro-costing model was utilised
      to generate costs for TBI. Costs were generated for two scenarios in which all
      moderate and severe TBI were admitted to ICU. The actual cost was then sub
      tracted from the scenario costs to establish the funding gap. RESULTS: During the
      period January 2012 to December 2014, a total of 3 301 patients were treated for
      TBI in PMB. The mean age was 30 years (SD 50). There were 2 632 (80%) males and
      564 (20%) females. The racial breakdown was overwhelmingly African (96%),
      followed by Asian (2%), Caucasian (1%) and mixed race (1%). There were 2 540 mild
      (GCS 13-15), 326 moderate (9-12), and 329 severe (GCS <=8) TBI admissions during
      the period under review. A total of 139 patients died (4.2%). A total of 242
      (7.3%) patients were admitted to ICU. Of these 137 (57%) had a GCS of 9 or less.
      A total of 2 383 CT scans were performed. The total cost of TBI over the two-year
      period was ZAR 62 million. If all 326 patients with moderate TBI had been
      admitted to ICU there would have been a further 281 ICU admissions. This was
      labelled Scenario 1. If all patients with severe as well as moderate TBI had been
      admitted there would have been a further 500 ICU admissions. This was labelled
      Scenario 2. Based on Scenario 1 and Scenario 2 the total cost would have been ZAR
      73 272 250 and ZAR 82 032 250 respectively. The funding gaps for Scenario 1 and
      Scenario 2 were ZAR 11 240 000 and ZAR 20 000 000 respectively. CONCLUSION: There
      is a significant burden of TBI managed by the PMTS. The cost of managing TBI each
      year is in the order of sixty million ZAR. A significant funding gap exists in
      our environment. This data does not include any data on the broader social costs
      of TBI. Investing in programs to reduce and prevent TBI is justified by the
      potential for significant savings.

PMID- 29227054
TI  - Auditing surgical service provision at a South African tertiary institution:
      Implications for the development of district services.
AB  - BACKGROUND: The optimal management of resources within South African state
      hospitals has been hampered by a paucity of data due to a lack of robust auditing
      information systems. This study reviews the use of a Hybrid Electronic Medical
      Record (HEMR) system to capture and aggregate data pertaining to the inpatient
      service demands on a South African tertiary surgical service. This dataset was
      used to analyse the appropriateness of tertiary surgical resource utilisation.
      METHOD: The HEMR system was implemented at Greys Hospital, in the city of
      Pietermaritzburg, Kwa-Zulu Natal, South Africa on 1 January 2013. Inpatient data
      pertaining to surgical admissions and operative interventions were captured
      prospectively. Following an 18-month study period, the data were extracted,
      aggregated and analysed. The district referral hospitals were mapped, and
      district surgical procedures performed within the tertiary center were identified
      and quantified. Results: 7314 patients were admitted and managed by the tertiary
      surgical service during the study period. The median patient age was 33 years
      (IQR 6.5-42.4 years). 59.7% were male and 40.3% were female. General, trauma and
      paediatric surgical admissions constituted 54.8%, 28.6% and 16.6% respectively.
      Emergency admissions constituted 62.4% and elective admissions 37.6%. Referral
      sources were captured for 6653 (91%) of the cohort. 4338 (65.2%) patients were
      referred from district hospitals. The district hospital (Northdale) closest to
      Greys Hospital was responsible for 1675 (25.2%) of surgical referrals. 4174
      operative procedures were performed during the study period, 54.7% performed as
      an emergency, 34.1% electively and 11.2% semi-electively. The median waiting time
      for emergency operative intervention was 535 minutes (IQR 130-663). A total of
      1272 (30.5%) operative procedures performed were assessed as district-level
      operations. The time intervals of 07:00-07:59 and 17:00-17:59 were identified as
      the time periods during which the least number of emergency procedures were
      performed in the operating theatres. CONCLUSION: The HEMR system enabled the
      Pietermaritzburg Metropolitan Department of Surgery to quantify the burden of
      surgical disease and map district referral patterns. Thirty percent of operative
      procedures performed were assessed as district-level operations. Potentially
      correctable deficits identified within the tertiary center were lengthy delays to
      emergency surgery and non-optimal theatre utilisation periods.

PMID- 29227055
TI  - Does the reporting of gastro-intestinal endoscopy meet the minimal terminology
      standard at King Edward VIII Hospital?
AB  - BACKGROUND: The Minimal Standard Terminology (MST) was developed to standardise
      endoscopic reporting. This study is aimed at assessing current reporting at a
      tertiary hospital and whether it meets this Minimal Standard Terminology. METHOD:
      This was a retrospective observational study of upper endoscopy reports between
      January and December 2014. The data extracted were compared to the current
      reporting standard listed in the MST. To assess and grade the quality of
      reporting we developed a Gastrointestinal Reporting Score, which incorporates MST
      variables in addition to demographic details, indication for endoscopy, report
      legibility, sedation and the use of classification systems to describe pathology.
      Variables were classified as blank, partially complete or complete and assigned a
      score of 1-3. The reports were graded according to their overall score for all
      variables (Max 40) into Grade A (> 36), B (28-36) and C (< 28). RESULTS: There
      were 100 patients of which 58 were female. Thirty-seven per cent were from the 60
      75 year age group. Fiftyfour endoscopies were performed by trainee specialists.
      Junior and senior consultants performed 36 and 9 upper endoscopies respectively.
      Indications for upper endoscopy were stated in 51 reports. The use of pre
      procedural sedation was not stated in 51 reports. Four reports were illegible;
      one was conducted by a junior consultant, two by a fourth year trainee specialist
      and one by an unknown endoscopist whose name was illegible. Common classification
      systems for oesophagitis, gastropathy features, ulcer characteristics, and ulcer
      location are not routinely used. Based on the Gastrointestinal Reporting Score
      there were no Grade A reports, 16 Grade B and 84 Grade C reports. CONCLUSION: The
      MST is not routinely utilised in our setting and reports are incomplete. There is
      a need for optimal upper endoscopic reporting, incorporating the MST guidelines.

PMID- 29227056
TI  - The value of supplementary anatomy workshops for improving undergraduate
      performance.
AB  - BACKGROUND: With many anatomy courses within the medical curriculum suffering
      reductions in lecture and dissection time, supplementary programs in anatomy have
      shown to improve performance of medical students. This study was conducted to
      evaluate the efficacy of anatomy workshops on undergraduate anatomy grade
      performance. METHOD: From 2012 to 2014, mean anatomy and physiology scores of
      medical students who attended anatomy workshops were compared to those who did
      not attend. Furthermore, mean scores in anatomy were also compared between
      students who attended one workshop to those who attended multiple workshops. Data
      analyses included comparing mean test scores using Student's t-test for normally
      distributed data. RESULTS: A total of 55 medical students were included in this
      study. Significant differences in both anatomy (p < 0.0001) and physiology (p =
      0.0113) scores were found between medical students who attended the anatomy
      workshops versus those who did not. Similarly, medical students who attended
      multiple workshops, compared to those that attended a single workshop, obtained
      significantly higher anatomy grade performance (p = 0.0043). CONCLUSION: The
      results of this study are supported by comparable studies that have shown similar
      improvements in grade performance. In a time where reduced undergraduate medical
      teaching time is prevalent, supplementary education in the basic sciences, with
      an emphasis on anatomy, may prove a successful adjunct to the medical curriculum.

PMID- 29227057
TI  - [Inferior ST elevation: beyond myocardial infarction].

PMID- 29227062
TI  - Epidemiology and Clinical Research for Chronic Kidney Disease.

PMID- 29227063
TI  - Interaction between Viral Proteins and Mitochondria.
AB  - Recent advances reveal that mitochondria are not limited to functioning only as
      the cellularpowerhouse and in apoptosis, but that they act as central hubs for
      multiple signal transductions.Studies over the last decade indicate that
      mitochondria in vertebrates are involved in the front line ofhost defense,
      especially against RNA viruses. Mitochondrial-mediated antiviral innate
      immunitydepends on activation of the retinoic acid-inducible gene I (RIG-I)-like
      receptors signal transductionpathway, and the mitochondrial surface acts as a
      platform for the assembly of signaling molecules,including mitochondrial
      antiviral signaling (MAVS) during the process. Some viral encoded proteinstarget
      to the mitochondria post-infection, however, thereby evading the cellular immune
      response.Here we review specific interactions between mitochondria and viral
      proteins and discuss theirphysiologic effects on the host cells.

PMID- 29227064
TI  - A case of Basaloid Follicular Hamartoma.
AB  - We here describe a case of solitary basaloid follicular hamartoma (BFH) : the
      case developing incompany with senile lentigo on the nose. BFH is a relatively
      rare benign follicular neoplasm ofundetermined etiology. Histologically, the
      specimen consisted of small-sized squamoid or basaloid cellsand follicular germ
      like cells in the periphery of the tumor nests. There were no infundibular
      cysts.BFH should be differentiated from infundibulocystic basal cell carcinoma
      (BCC), which consists ofsquamoid or basaloid cells in company with infundibular
      cysts, tumor of follicular infundibulum ortrichoepithelioma. We analyzed the
      immunohistochemical findings of the case in comparison withthose of BCC and
      trichoepithelioma. An immunohistochemical examination revealed 1) that Bcl-2
      andCD10 was preferentially expressed in the outermost cells in the tumor nests
      consisting of folliculargerm-like cells, 2) that most of the tumor cells,
      especially germ-like cells, were strongly positive forBer-EP4, and 3) that
      peritumoral stroma was positive for CD34. The immunohistochemical findings ofour
      cases supported that BFH should be differentiated from BCC, a common malignant
      neoplasm.

PMID- 29227065
TI  - Theoretical Models of Vascular Pattern Formation.
AB  - Pattern formation of vascular structure has been extensively studied in vascular
      biology. Classicallythe pattern formation process falls into three categories
      vasculogenesis, angiogenesis and remodeling.Mathematical modeling study of these
      phenomena has been done byrelatively independent ofexperimental works by applied
      mathematicians, and not well understood by experimental biologists. Inthis review
      I provide intuitive explanations of proposed theoretical models and recent
      advance inmodelling study of vascular development.

PMID- 29227066
TI  - Anatomical Comparison between Rodent and Avian Circuits for Vocal Communication.

PMID- 29227067
TI  - Role of Natural Killer T Cells in Cardiac Remodeling and Failure and the
      Development of Novel Therapeutic Strategy.
AB  - Chronic inflammation in the myocardium is involved in the development of left
      ventricular (LV)remodeling and failure after myocardial infarction (MI).
      Invariant natural killer T (iNKT) cells havebeen shown to produce inflammatory
      cytokines and orchestrate tissue inflammation. However, noprevious studies have
      determined the pathophysiological role of iNKT cells in post-MI LV remodeling.We
      thus examined whether the activation of iNKT cells might affect the development
      of LVremodeling and failure. After creation of MI, mice received the injection of
      either a-galactosylceramide(aGC), the activator of iNKT cells, or phosphate
      buffered saline 1 and 4 days after surgery, andwere followed during 28 days.
      Survival rate was significantly higher in MI +aGC than MI + PBS. LVcavity
      dilatation and dysfunction were significantly attenuated inMI +aGC, despite
      comparable infarctsize, accompanied by a decrease in myocyte hypertrophy,
      interstitial fibrosis, and apoptosis. Theinfiltration of iNKT cells were
      increased during early phase in noninfarcted LV from MI and aGCfurther enhanced
      them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days,
      whichpersisted until 28 days. AntiIL-10 receptor antibody abrogated these
      protective effects of aGC on MIremodeling. The administration of aGC into iNKT
      cell-deficient Ja18(-/-) mice had no such effects,suggesting that aGC was a
      specific activator of iNKT cells. iNKT cells play a protective role againstpost
      MI LV remodeling and failure through the enhanced expression of cardioprotective
      cytokinessuch as IL-10.

PMID- 29227068
TI  - Portal Vein Thrombosis Repeatedly Observed in a Cirrhotic Patient with
      Antiphospholipid Antibody Syndrome.
AB  - Background: Although portal vein thrombosis in cirrhotic patients is frequently
      observed, thedetailed process remains to be clarified, and the role of
      anticardiolipin antibody in the development ofportal vein thrombosis has been
      controversial. Case Report: A 52-year-old man, who had been diagnosed with
      alcoholic cirrhosis of the liver, wasadmitted to our hospital suffering from
      dyspnea and ascites. Just after being diagnosed as havingantiphospholipid
      antibody syndrome with lung thrombosis and delivering a positive result for the
      beta2-glycoprotein I-dependent anticardiolipin antibody, he sustained rupture of
      the esophageal variceswith rapid development of portal vein thrombosis, which
      resolved under anticoagulant therapy. Twoyears later, he was admitted again on
      suspicion of thrombosis because of an elevation in the serumD-dimer level, and
      computed tomography showed portal and upper mesenteric vein thrombosis.Although
      immediate anticoagulant therapy resulted in complete recanalization, he suffered
      the sameepisode 2 months later, which occurred with re-elevation of the serum D
      dimer level. Conclusion: A positive finding of an anticardiolipin antibody in
      cirrhotic patients has been consideredto be nonspecific and not related to the
      development of thrombus in the portal vein. This case,however, seems to indicate
      that cirrhotic patients with the beta2-glycoprotein I-dependentanticardiolipin
      antibody should be regarded as being at high risk for portal vein thrombosis.
      Monitoringwith the serum D-dimer was useful in detecting portal vein thrombosis
      in its early stage.

PMID- 29227069
TI  - Molecular Mechanism of Lifestyle-related Diseases : See Both the Wood and Trees!
AB  - Energy homeostasis is maintained locally through parenchymal-stromal cell
      interaction and systemically through metabolic organ network. In obese adipose
      tissue, saturated fatty acids, which are released as a danger signal from
      hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating
      macrophages, thus establishing a vicious cycle between adipocytes and macrophages
      to stimulate adipose tissue inflammation. Histologically, macrophages aggregate
      to constitute crown-like structures (CLS), where they are thought to scavenge the
      residual lipid droplets of dead adipocytes. Free fatty acids, when released from
      obese visceral fat depots, are transported in large quantities to the liver via
      the portal vein, where they are accumulated as ectopic fat, thus developing non
      alcoholic fatty liver disease (NAFLD). There is a unique histological feature
      termed/hepatic CLS (hCLS)oin the non-alcoholic steatohepatitis (NASH) liver,
      where macrophages aggregate to surround dead hepatocytes with large lipid
      droplets. Notably, the number of hCLS is positively correlated with the extent of
      liver fibrosis. Our data suggest that hCLS serves as an origin of hepatic
      inflammation and fibrosis during the progression from simple steatosis to NASH.
      Sodium glucose cotransporter 2 (SGLT2) inhibitors, an oral antidiabetic drug,
      promotes the urinaryexcretion of glucose by blocking its reabsorption in renal
      proximal tubules. Inhibition of SGLT2 lowers is expected to reduce body weight
      because of urinary calorie loss. Interestingly, SGLT2 inhibitionimproves hepatic
      steatosis in obese mice irrespective of body weight reduction. There is an
      inverse correlation between liver weight and adipose tissue weight in obese mice
      with SGLT2 inhibition, suggesting that SGLT2 inhibition induces
      the/healthyoadipose tissue expansion and prevents ectopic fat accumulation in the
      liver. Our data suggest that seeing both the wood and trees is Required to
      understand the molecular mechanism of lifestyle-related diseases.

PMID- 29227070
TI  - Immunohistological Localization of Peroxisome Proliferator-Activated Receptor
      alpha and gamma in Human Sebaceous Glands.
AB  - The immunohistological localization of peroxisome proliferator-activated receptor
      a (PPARa) and PPAR g was examined in 28 pilosebaceous units in 10 paraffin
      embedded normal human skin specimens. Rabbit polyclonal antibody against human
      PPARa and monoclonal antibody against human PPARg were used as specific primary
      antibodies. The nuclear and cytoplasmic expression of PPARa was detected in basal
      to differentiated sebocytes. In contrast, the expression of PPARg was confined to
      nuclei of suprabasal to early-differentiated sebocytes. The nuclear PPARg
      expression was present only occasionally in the basal sebocytes. These results
      suggest that PPARa and PPARg are integral parts of sebocyte differentiation in
      human sebaceous glands.

PMID- 29227071
TI  - Natural Immunity and Ocular Inflammation.
AB  - We have focused on the role of innate immunity during the formation ofochoroidal
      neovascularization(CNV) -related diseasesu. Inflammation affects the formation
      and the progression of variousvitreoretinal diseases. We performed a
      comprehensive analysis of inflammatory immune mediators inthe vitreous fluids
      with diabetic macular edema, proliferative diabetic retinopathy, branch retinal
      veinocclusion, central retinal vein occlusion and rhegmatogenous retinal
      detachment. The concentrationsof 20 soluble factors (nine cytokines, six
      chemokines, and five growth factors) were measuredsimultaneously by multiplex
      bead analysis system. Out of 20 soluble factors, three factors :interleukin-6 (IL
      6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1)
      weresignificantly elevated in all groups of vitreoretinal diseases compared with
      control group. According tothe correlation analysis in the individual patient's
      level, these three factors that were simultaneouslyincreased, did not show any
      independent upregulation in all the examined diseases.We also elucidated the role
      of natural killer (NK)T cells, which restricted CD1 molecule andparticipate in
      the innate immune response, in laser-induced experimental CNV. We examined
      CNVformation in independent two NKT cell-deficient mice, either CD1 knockout (KO)
      mice or Ja18 KOmice, and found that both KO mice showed significant reduction of
      experimental CNV.During the clinical process of CNV-related diseases, not only
      CNV formation, subretinal scaring isthought to be another important step. We thus
      established the experimental model of subretinalscaring by injecting peritoneal
      exudating macrophages into subretinal space. Subretinal fibrous tissuewas
      observed by fundus scope in PEC-inoculated mice after seven days. The tissue was
      consisted ofmonotonous and low cell-density area, which expressed a-SMA with
      collagen synthesis. BecausePEC-inoculated MCP-1 KO mice showed less amount of
      glial residual, not only exogenousmacrophages, but also intrinsic macrophages are
      critical. Activated macrophages directly inducedmyofibrotic changes in RPE cells
      in vitro.

PMID- 29227072
TI  - The Present Situation and Clinical Topics of Ventricular Assist Device and Heart
      Transplantation in Japan.
AB  - Surgical treatment for heart failure includes coronary artery bypass grafting to
      ischemic heartdisease, valvular disease surgery such as mitral valvuloplasty,
      left ventricular restoration, ventricularassist device (VAD), and heart
      transplantation. In addition, HeartSheet which is regenerative medicineusing
      autologous skeletal myoblast sheets has been started from the spring of 2016.
      Formal insurancereimbursement of implantable LVAD was obtained in April 2011, and
      the life prognosis of patientswith severe heart failure improved markedly.
      However, the indication for implantable LVAD is limitedto bridge use for heart
      transplantation. Implantable LVAD cannot be implanted in patients over 65years
      old under health insurance because the adaptive age of heart transplantation in
      Japan is under 65years old. It is a problem that the indication of implantable
      LVAD is identical to that of hearttransplantation. Clinical trial of destination
      therapy is in progress for the purpose of optimizing theimplantable LVAD
      indication. I strongly pray that VAD treatment including destination therapy
      (DT)and transplant medical treatment based on good intentions will be accepted
      socially as generaltreatment.

PMID- 29227073
TI  - The effect of amixin and agmatine on cytochrome C release from isolated
      mitochondria
AB  - Mitochondrial nicotinic acetylcholine receptors (nAChRs) control permeability
      transition pore formationand cytochrome c release in the presence of apoptogenic
      factors. This study demonstrates that pharmacologicalagents amixin and agmatine
      affect mitochondrial nAChR functioning: they slightly suppresscytochrome c
      release from mouse brain and liver mitochondria stimulated with apoptogenic dose
      of Sa2+ andprevent the effect of alpha7 nAChR agonist PNU282987. We conclude that
      mitochondria may be one of therapeutictargets of amixin and agmatine.

PMID- 29227074
TI  - Hypoxic regulation of the expression of cell proliferation related genes in U87
      glioma cells upon inhibition of ire1 signaling enzyme
AB  - We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1),
      which is a centralmediator of endoplasmic reticulum stress and a controller of
      cell proliferation and tumor growth, on hypoxicregulation of the expression of
      different proliferation related genes in U87 glioma cells. It was shown
      thathypoxia leads to up-regulation of the expression of IL13RA2, CD24, ING1,
      ING2, ENDOG, and POLG genesand to down-regulation - of KRT18, TRAPPC3, TSFM, and
      MTIF2 genes at the mRNA level in control gliomacells. Changes for ING1 and CD24
      genes were more significant. At the same time, inhibition of IRE1 modifiesthe
      effect of hypoxia on the expression of all studied genes. In particular, it
      increases sensitivity to hypoxiaof the expression of IL13RA2, TRAPPC3, ENDOG, and
      PLOG genes and suppresses the effect of hypoxia onthe expression of ING1 gene.
      Additionally, it eliminates hypoxic regulation of KRT18, CD24, ING2, TSFM,and
      MTIF2 genes expressions and introduces sensitivity to hypoxia of the expression
      of BET1 gene in gliomacells. The present study demonstrates that hypoxia, which
      often contributes to tumor growth, affects theexpression of almost all studied
      genes. Additionally, inhibition of IRE1 can both enhance and suppress thehypoxic
      regulation of these gene expressions in a gene specific manner and thus possibly
      contributes to slowerglioma growth, but several aspects of this regulation must
      be further clarified.

PMID- 29227075
TI  - Multiple parametric approaches to assess acute radiation lung injury of rats
      radiation lung injury of rats.
AB  - The effect of whole body gamma irradiation (WBI) in single fraction was studied,
      as well as its influenceon the secretion of various biochemical markers and
      cellular component that could be used as acute radiationlung injury marker.
      Sprague dawley rats were treated with WBI (60Co) of radiation dose from 1 Gy to 5
      Gy(dose rate - 0.95 Gy/min). Bronchoalveolar lavage fluid was retrieved from all
      animals in control and radiationtreated groups up to 72 h post radiation.
      Bronchoalveolar lavage fluid (BALF) was analyzed for lactatedehydrogenase (LDH ),
      acid phosphatase (AP ), alkaline phosphatase (ALP ), cell count and total
      protein. Intragroupand intergroup comparison of BALF parameters at different
      radiation doses showed significant difference.LDH was significantly increased as
      the dose increased from 1Gy to 5Gy (P = 0.00) after 2 h with effectsize of
      difference (r > 0.3). ALP was significantly altered after 3Gy and 4Gy (P < 0.05).
      AP was significantlyaltered at 2Gy-5Gy (p < 0.05). Total protein level changed
      significantly from 1Gy to 5Gy (P < 0.00). Cellularcontent of BALF showed
      significant changes after radiation exposure. BALF parameters like LDH, AP,
      ALP,neutrophils, lymphocytes, total leukocyte count and total protein were
      sensitive to radiation exposure andtheir levels vary significantly up to 72 h
      after single whole body radiation exposure in Sprague dawley rats.It can be
      concluded that the biochemical indices in BALF have more wide application in
      evaluation of acuteradiation induced lung injury.

PMID- 29227076
TI  - Evaluation of functioning of mitochondrial electron transport chain with NADH and
      FAD autofluorescence
AB  - We prove the feasibility of evaluation of mitochondrial electron transport chain
      function in isolatedmitochondria of smooth muscle cells of rats from uterus using
      fluorescence of NADH and FAD coenzymes.We found the inversely directed changes in
      FAD and NADH fluorescence intensity under normal functioningof mitochondrial
      electron transport chain. The targeted effect of inhibitors of complex I, III and
      IV changedfluorescence of adenine nucleotides. Rotenone (5 MUM) induced rapid
      increase in NADH fluorescence dueto inhibition of complex I, without changing in
      dynamics of FAD fluorescence increase. Antimycin A, acomplex III inhibitor, in
      concentration of 1 MUg/ml caused sharp increase in NADH fluorescence and
      moderateincrease in FAD fluorescence in comparison to control. NaN3 (5 mM), a
      complex IV inhibitor, and CCCP(10 MUM), a protonophore, caused decrease in NADH
      and FAD fluorescence. Moreover, all the inhibitorscaused mitochondria swelling.
      NO donors, e.g. 0.1 mM sodium nitroprusside and sodium nitrite similarlyto the
      effects of sodium azide. Energy-dependent Ca2+ accumulation in mitochondrial
      matrix (in presenceof oxidation substrates and Mg-ATP2- complex) is associated
      with pronounced drop in NADH and FADfluorescence followed by increased
      fluorescence of adenine nucleotides, which may be primarily due to Ca2+-dependent
      activation of dehydrogenases of citric acid cycle. Therefore, the fluorescent
      signal of FAD andNADH indicates changes in oxidation state of these nucleotides
      in isolated mitochondria, which may be usedto assay the potential of effectors of
      electron transport chain.

PMID- 29227078
TI  - Overtime 'Parking' Must Be Addressed.

PMID- 29227077
TI  - Modulation of cisplatin-induced reactive oxygen species production by fullerene
      C(60) in normal and transformed lymphoid cells
AB  - The early response of normal (Wistar rat thymocytes) and transformed (mice
      lymphoid leukemiaL1210) cells to treatment with anticancer drug cisplatin or to
      combined treatment with cisplatin and carbonnanostructure fullerene C60 was
      studied. We demonstrated with fluorescent probes DCFH-DA and TMRE thatcisplatin
      at concentration 1 MUg/ml induced reactive oxygen species (ROS) production and
      decreased the valueof mitochondrial membrane potential in both cell types. The
      combined treatment with cisplatin (1 MUg/ml) andfullerene C60 (7.2 MUg/ml) was
      shown to be followed by oppositely directed modulation of ROS production
      inthymocytes and L1210 cells. Cisplatin-induced ROS production was intensified in
      L1210 cells, while in thymocytesit was decreased. It is supposed that the
      different effects of combined treatment are associated withpeculiarities of
      fullerene C60 accumulation and localization in normal and cancer cells.

PMID- 29227080
TI  - Big Data, The Law and You: Embracing data can reduce potential liability.

PMID- 29227079
TI  - Biochemical indicators of nephrotoxicity in blood serum of rats treated with
      novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol
      containing nanoscale polymeric carrier
AB  - The aim of this study was to compare the effect of new synthetic 4-thiazolidinone
      derivatives (potentialanticancer compounds denoted as 3882, 3288 and 3833) and
      doxorubicin (positive control) in free form and intheir complexes with synthetic
      polyethylene glycol-containing nanoscale polymeric carrier on the
      biochemicalindicators of nephrotoxicity in blood serum of rats. The concentration
      of total protein, urea, creatinine,glucose, ions of sodium, potassium, calcium,
      iron and chloride was measured. It was found that after injectionof the
      investigated compounds, the concentration of sodium cations and chloride anions
      in blood serum wasincreased compared with control (untreated animals).
      Doxorubicin's injection was accompanied by a decreasein the concentration of iron
      cations. The concentration of total protein, urea and creatinine decreased
      underthe influence of the studied compounds. Complexation of these antineoplastic
      substances with a syntheticpolymeric nanocarrier lowered the concentration of the
      investigated metabolites substantially compared tothe effect of these compounds
      in free form. The normalization of concentration of total protein, urea
      andcreatinine in blood serum of rats treated with complexes of the studied
      compounds with the polymeric carriercomparing with increased concentration of
      these indicators at the introduction of such compounds in freeform was found.

PMID- 29227081
TI  - Prx II and CKBB proteins interaction under physiologic al and thermal stress
      conditions in A549 and HeLa cells.
AB  - Peroxiredoxins (Prxs) are versatile enzymes that demonstrate various cell
      functions as peroxidases,protein chaperones, functions of signal modulators and
      binding partners. It is well established that Prxs caninteract with multiple
      proteins in cells, such as ASK1, Cdk5-p35, JNK, MIF, PDGF, TK R4 and others. In
      thisstudy, we attempted to evaluate a possible association between ubiquitous Prx
      II and ATP/ADP bufferingenzyme - brain-type creatine kinase (CK BB). Our co
      immunoprecipitation (Co-IP) results from the A549and HeLa cell lysates with
      overexpressed HA-Prx II and Flag-CK BB have demonstrated strong
      associationbetween two proteins under non-stressed conditions. This protein
      interaction was enhanced by the heat treatmentwith further HA-Prx II
      precipitation to the immobilized Flag-CK BB depending on the temperature
      increase.Temperature induced oligomerization of Prx II may contribute to the
      formation of Prx II conglomerates,which in turn, can associate with CK BB and
      increase signal intensities on the blotted membranes. Thus,such association and
      oligomerization of Prx II could take part in recovery and protection of the CK BB
      enzymeactivity from inactivation during heat-induced stress.

PMID- 29227082
TI  - Chitotriosidase activity as additional biomarker in the diagnosis of lysosomal
      storage diseases.
AB  - To date, several genetic variants that lead to a deficiency of chitotriosidase
      activity have beendescribed. The duplication of 24 bp (dup24bp) in exon 10 of the
      CHIT1 gene, which causes a complete loss ofenzymatic activity of the gene
      product, is the most common among the European population. The aim of thestudy
      was to evaluate the possibility of using chitotriosidase activity as an
      additional biomarker in diagnosisof lysosomal storage diseases (LSDs) in Ukraine,
      to determine this parameter in blood plasma of the patientswith various lysosomal
      diseases and to assess the effect of the presence of dup24bp in the CHIT1 gene
      onthis parameter. It has been shown that chitotriosidase activity in blood plasma
      is a convenient additionalbiochemical marker in the diagnosis of some LSDs,
      namely Gaucher disease, Niemann-Pick disease A, B, Cand GM1-gangliosidosis.
      Reference ranges of the normal chitotriosidase activity were determined in
      bloodplasma of Ukrainian population and found to be 8.0-53.1 nmol 4
      methylumbelliferone/h.ml of plasma. Thetotal allele frequency of the dup24bp in
      the CHIT1 gene in Ukrainian population was determined, whichamounted to 0.26
      (323/1244) that is higher than in European population. It was indicated that
      moleculargeneticscreening of dup24bp in the CHIT1 gene is a necessary stage in a
      protocol for the laboratory diagnosisof Gaucher disease, Niemann-Pick disease A,
      B, C as well as GM1-gangliosidosis to avoid incorrect diagnosis.

PMID- 29227083
TI  - All of the Stuff: Avoid drowning in the sea of diagnostic tools.

PMID- 29227084
TI  - Amine oxidases as important agents of pathological processes of rhabdomyolysis in
      rats.
AB  - In this study we have tested an idea on the important role of amine oxidases
      (semicarbazide-sensitiveamine oxidase, diamine oxidase, polyamine oxidase) as an
      additional source of oxidative/carbonyl stressunder glycerol-induced
      rhabdomyolysis, since the enhanced formation of reactive oxygen species and
      reactivecarbonyl species in a variety of tissues is linked to various diseases.
      In our experiments we used the sensitivefluorescent method devised for estimation
      of amine oxidases activity in the rat kidney and thymus as targetedorgans under
      rhabdomyolysis. We have found in vivo the multiple rises in activity of
      semicarbazide-sensitiveamine oxidase, diamine oxidase, polyamine oxidase (2-4.5
      times) in the corresponding cell fractions, wholecells or their lysates at the 3
      6th day after glycerol injection. Aberrant antioxidant activities depended
      onrhabdomyolysis stage and had organ specificity. Additional treatment of animals
      with metal chelator 'Unithiol'adjusted only the activity of antioxidant enzymes
      but not amine oxidases in both organs. Furthermore the invitro experiment showed
      that Fenton reaction (hydrogen peroxide in the presence of iron) products alone
      hadno effect on semicarbazide-sensitive amine oxidase activity in rat liver cell
      fraction whereas supplementationwith methylglyoxal resulted in its significant
      2.5-fold enhancement. Combined action of the both agents hadadditive effect on
      semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine
      andpolyamine catabolism by amine oxidases is upregulated by oxidative and
      carbonyl stress factors directlyunder rhabdomyolysis progression, and the
      increase in catabolic products concentration contributes to tissuedamage in
      glycerol-induced acute renal failure and apoptosis stimulation in thymus.

PMID- 29227085
TI  - Photoinduced Bandgap Renormalization and Exciton Binding Energy Reduction in WS2.
AB  - Strong Coulomb attraction in monolayer transition metal dichalcogenides gives
      rise to tightly bound excitons and many-body interactions that dominate their
      optoelectronic properties. However, this Coulomb interaction can be screened
      through control of the surrounding dielectric environment as well as through
      applied voltage, which provides a potential means of tuning the bandgap, exciton
      binding energy, and emission wavelength. Here, we directly show that the bandgap
      and exciton binding energy can be optically tuned by means of the intensity of
      the incident light. Using transient absorption spectroscopy, we identify a sub
      picosecond decay component in the excited-state dynamics of WS2 that emerges for
      incident photon energies above the A-exciton resonance, which originates from a
      nonequilibrium population of charge carriers that form excitons as they cool. The
      generation of this charge-carrier population exhibits two distinct energy
      thresholds. The higher threshold is coincident with the onset of continuum states
      and therefore provides a direct optical means of determining both the bandgap and
      exciton binding energy. Using this technique, we observe a reduction in the
      exciton binding energy from 310 +/- 30 to 220 +/- 20 meV as the excitation
      density is increased from 3 * 1011 to 1.2 * 1012 photons/cm2. This reduction is
      due to dynamic dipolar screening of Coulomb interactions by excitons, which is
      the underlying physical process that initiates bandgap renormalization and leads
      to the insulator-metal transition in monolayer transition metal dichalcogenides.

PMID- 29227086
TI  - Chemical Foaming Coupled Self-Etching: A Multiscale Processing Strategy for
      Ultrahigh-Surface-Area Carbon Aerogels.
AB  - Due to the unique structure, carbon aerogels have always shown great potential
      for multifunctional applications. At present, it is highly desirable but remains
      challenging to tailor the microstructures with respect to porosity and specific
      surface area to further expand its significance. A facile chemical foaming
      coupled self-etching strategy is developed for multiscale processing of carbon
      aerogels. The strategy is directly realized via the pyrolysis of a
      multifunctional precursor (pentaerythritol melamine phosphate) without any
      special drying process and multiple steps. In the micrometer scale, the
      macroporous scaffold structures with interconnected and strutted carbon
      nanosheets are built up by chemical foaming from decomposition of melamine,
      whereas the meso/microporous nanosheets are formed via self-etching by phosphorus
      containing species. The delicately hierarchical structures and record-breaking
      specific surface area of 2668.4 m2 g-1 render the obtained carbon aerogels great
      potentials for absorption (324.1-593.6 g g-1 of absorption capacities for varied
      organic solvents) and energy storage (338 F g-1 of specific capacitance). The
      construction of such novel carbon nanoarchitecture will also shed light on the
      design and synthesis of multifunctional materials.

PMID- 29227088
TI  - Host-Guest Interaction Creates Hydrogen-Evolution Electrocatalytic Active Sites
      in 3d Transition Metal-Intercalated Titanates.
AB  - The hydrogen evolution reaction (HER) is involved in energy-intensive water- and
      chlor-alkali electrolyzers, and thus, highly active and stable HER
      electrocatalysts in alkaline media are needed. Titanates, a family of
      representative two-dimensional materials with negatively charged main layers, are
      chemically and structurally stable under strongly basic conditions, but they have
      never been shown to have electrocatalytic activity for HER. Herein, we report
      that intercalating 3d metal cations, including Fe3+, Co2+, Ni2+, and Cu2+ ions,
      into the interlayer regions of titanates yields efficient and robust
      electrocatalysts for the alkaline HER. The intercalation of 3d metal cations in
      titanates is achieved by rapid cation-exchange reaction between Na+-containing
      titanates and 3d metal cations at room temperature. Among the 3d metal
      intercalated titanates we synthesize, the Co2+-containing material is found to
      show the best electrocatalytic activity. Experimental and theoretical results
      reveal that the strong electronic interaction between 3d metal cations and
      negatively charged main [TiO6]infinity layers renders good catalytic activity to
      the outermost oxygen atoms in the [TiO6]infinity layer, further making 3d metal
      intercalated titanate an efficient electrocatalyst for the HER.

PMID- 29227087
TI  - New Application of Neomycin B-Bisbenzimidazole Hybrids as Antifungal Agents.
AB  - Alkylated aminoglycosides and bisbenzimidazoles have previously been shown to
      individually display antifungal activity. Herein, we explore for the first time
      the antifungal activity (in liquid cultures and in biofilms) of ten alkylated
      aminoglycosides covalently linked to either mono- or bisbenzimidazoles. We also
      investigate their toxicity against mammalian cells, their hemolytic activity, and
      their potential mechanism(s) of action (inhibition of fungal ergosterol
      biosynthetic pathway and/or reactive oxygen species (ROS) production). Overall,
      many of our hybrids exhibited broad-spectrum antifungal activity. We also found
      them to be less cytotoxic to mammalian cells and less hemolytic than the FDA
      approved antifungal agents amphotericin B and voriconazole, respectively.
      Finally, we show with our best derivative (8) that the mechanism of action of our
      compounds is not the inhibition of ergosterol biosynthesis, but that it involves
      ROS production in yeast cells.

PMID- 29227089
TI  - Expanding the Bioactive Chemical Space of Anthrabenzoxocinones through
      Engineering the Highly Promiscuous Biosynthetic Modification Steps.
AB  - Anthrabenzoxocinones (ABXs) including (-)-ABXs and (+)-ABXs are a group of
      bacterial FabF-specific inhibitors with potent antimicrobial activity of
      resistant strains. Optimization of their chemical structures is a promising
      method to develop potent antibiotics. Through biosynthetic investigation, we
      herein identified and characterized two highly promiscuous enzymes involved in
      the (-)-ABX structural modification. The promiscuous halogenase and
      methyltransferase can respectively introduce halogen-modifications into various
      positions of the ABX scaffolds and methylation to highly diverse substrates.
      Manipulation of their activity in both of the (-)-ABXs and (+)-ABXs biosyntheses
      led to the generation of 14 novel ABX analogues of both enantiomers. Bioactivity
      assessment revealed that a few of the analogues showed significantly improved
      antimicrobial activity, with the C3-hydroxyl and chlorine substitutions critical
      for their activity. This study enormously expands the bioactive chemical space of
      the ABX family and FabF-specific inhibitors. The disclosed broad-selective
      biosynthetic machineries and structure-activity relationship provide a solid
      basis for further generation of potent antimicrobial agents.

PMID- 29227090
TI  - Electrochemical Sensing of Hydrogen Peroxide Using Block Copolymer Templated Iron
      Oxide Nanopatterns.
AB  - A new enzyme-free sensor based on iron oxide (Fe3O4) nanodots fabricated on an
      indium tin oxide (ITO) substrate via a block copolymer template was developed for
      highly sensitive and selective detection of hydrogen peroxide (H2O2). The self
      assembly-based process described here for Fe3O4 formation is a simple, cost
      effective, and reproducible process. The H2O2 response of the fabricated
      electrodes was linear from 2.5 * 10-3 to 6.5 mM with a sensitivity of 191.6 MUA
      mM-1cm-2 and a detection limit of 1.1 * 10-3 mM. The electrocatalytic activity of
      Fe3O4 nanodots toward the electroreduction of H2O2 was described by cyclic
      voltammetric and amperometric techniques. The sensor described here has a strong
      anti-interference ability to a variety of common biological and inorganic
      substances.

PMID- 29227091
TI  - Vacuum-Ultraviolet-Excited and CH2Cl2/H2O-Amplified Ionization-Coupled Mass
      Spectrometry for Oxygenated Organics Analysis.
AB  - The mass spectrometry analysis of oxygenated volatile organic compounds (OVOCs)
      remains challenging due to their limited ionization efficiencies. In this study,
      we surprisingly found that, under vacuum-UV (VUV) excitation, a gaseous mixture
      of CH2Cl2/H2O/analyte (OVOCs) in N2 buffer generated large amounts of H3O+ and
      protonated analyte even when the photon energy was lower than the ionization
      energy of the neutral species involved. In contrast to those obtained with VUV
      photoionization alone, the signal intensities of oxygenated organics can be
      amplified by more than 3 orders of magnitude. The isotope tracing experiment
      revealed that the proton donor is water, and the dependence of the signal
      intensities on the VUV photon intensities verified that the reaction was a single
      photon process. The observed ionization process is assigned as an undocumented
      chemi-ionization reaction in which a complex formed from the ion-pair state
      CH2Cl2*, H2O, and analyte and then autoionized to produce the protonated analyte
      with the aid of the reorganization energy released from the formation of CH2O and
      HCl. Essentially, here we present an efficient chemi-ionization method for the
      direct protonation of oxygenated organics. By the method, the mass spectrometric
      sensitivities toward acetic acid, ethanol, aldehyde, diethyl ether, and acetone
      were determined to be 224 +/- 17, 245 +/- 5, 477 +/- 14, 679 +/- 11, and 684 +/-
      6 counts pptv-1, respectively, in 10 s acquisition time. In addition, the present
      ionization process provides a new method for the generation of a high-intensity
      H3O+ source (~1011 ions s-1, measured by ion current) by which general organics
      can be indirectly protonated via a conventional proton-transfer reaction. These
      results open new aspects of chemi-ionization reactions and offer new
      technological applications that have the potential to greatly improve mass
      spectrometry sensitivity for detecting trace gaseous organics.

PMID- 29227092
TI  - Sandwich-Type Electrochemiluminescence Sensor for Detection of NT-proBNP by Using
      High Efficiency Quench Strategy of Fe3O4@PDA toward Ru(bpy)32+ Coordinated with
      Silver Oxalate.
AB  - Heart failure (HF) is a burgeoning public health problem trigged by a heart
      circulation disorder. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has
      been acknowledged as a prognostic biomarker for cardiac disease. Herein, a
      sandwich-type electrochemiluminescence (ECL) immunosensor was introduced for
      sensitive detection of NT-proBNP. Gold nanoparticle modified graphene oxide
      Ru(bpy)32+/Ag2C2O4 was used as a luminophore and a desirable platform for
      immobilization of the captured antibodies. The more stable immobilization of
      plentiful Ru(bpy)32+ could be implemented by direct covalent bonding chelation
      with Ag2C2O4. More importantly, significant quenching can be achieved by
      introducing polydopamine (PDA) coated Fe3O4 onto the electrode via sandwich
      immunoreactions. The quenching mechanism mainly showed that the excited states of
      Ru(bpy)32+ could be annihilated by quinone units in PDA via energy transfer. The
      ECL quenching efficiency was logarithmically related to the concentration of the
      NT-proBNP in the range from 0.0005 ng/mL to 100.0 ng/mL with a detection limit of
      0.28 pg/mL. Furthermore, this specific immunosensor presented good stability and
      repeatability as well as selectivity, which offers a guiding significance in both
      fundamental and clinical diagnosis of NT-proBNP.

PMID- 29227093
TI  - Modeling Spin Interactions in a Triangular Cobalt(II) Complex with
      Triaminoguanidine Ligand Framework: Synthesis, Structure, and Magnetic
      Properties.
AB  - The new tritopic triaminoguanidine-based ligand 1,2,3-tris[(pyridine-2
      ylmethylidene)amino]guanidine (H2pytag) was synthesized. The reaction of a
      mixture of cobalt(II) chloride and cobalt(II) perchlorate with the ligand H2pytag
      in pyridine solution leads to the formation of the trinuclear cobalt(II) complex
      [Co3(pytag)(py)6Cl3]ClO4. Three octahedrally coordinated high-spin cobalt(II)
      ions are linked through the bridging triaminoguanidine backbone of the ligand
      leading to an almost equilateral triangular arrangement. The magnetic properties
      of the complex were investigated by magnetic measurements, variable-temperature,
      variable-field magnetic circular dichroism (MCD) spectroscopy, and density
      functional theory as well as ab initio calculations. A rather strong
      antiferromagnetic exchange interaction between the cobalt(II) centers of ca. -12
      cm-1 is determined together with a strong local anisotropy. The single-ion
      anisotropy of all three cobalt(II) centers is found to be easy-plane, which
      coincides with the tritopic ligand plane. MCD measurements and theoretical
      investigations demonstrate the presence of rhombic distortion of the local Co
      surrounding.

PMID- 29227094
TI  - Synthesis and Electronic Properties of Fluoreno[2,1-a]fluorenedione and
      Fluoreno[1,2-a]fluorenedione.
AB  - The [2,1-a]- and [1,2-a]-isomers of fluorenofluorenedione have been synthesized
      via intramolecular Friedel-Crafts acylations. DFT calculations indicate that the
      [1,2-a]-isomer adopts a twisted, helical C2-symmetric structure and that its
      protonated form is the thermodynamic product of the Friedel-Crafts acylation in
      hot sulfuric acid. Absorption spectroscopy and cyclic voltammetry measurements
      provide experimental estimations of frontier molecular orbital energy levels,
      which are reported and discussed.

PMID- 29227095
TI  - Four-Component Catalytic Machinery: Reversible Three-State Control of
      Organocatalysis by Walking Back and Forth on a Track.
AB  - A three-component supramolecular walker system is presented where a two-footed
      ligand (biped) walks back and forth on a tetrahedral 3D track upon the addition
      and removal of copper(I) ions, respectively. The addition of N-methylpyrrolidine
      as a catalyst to the walker system generates a four-component catalytic
      machinery, which acts as a three-state switchable catalytic ensemble in the
      presence of substrates for a conjugate addition. The copper(I)-ion-initiated
      walking process of the biped ligand on the track regulates the catalytic activity
      in three steps: ON versus intON (intermediate ON) versus OFF. To establish the
      operation of the four-component catalytic machinery in a mixture of all
      constituents, forward and backward cycles were performed in situ illustrating
      that both the walking process and catalytic action are fully reversible and
      reproducible.

PMID- 29227096
TI  - Development and Characterization of a Soybean Experimental Line Lacking the
      alpha' Subunit of beta-Conglycinin and G1, G2, and G4 Glycinin.
AB  - A soybean experimental line (BSH-3) devoid of a subset of seed storage proteins
      was developed by crossing a mutant donor line "HS99B" with a Chinese cultivar
      "Dongnong47" (DN47). One-dimensional and high-resolution 2-D gel electrophoresis
      revealed the absence of G1 (A1aB2), G2 (A2B1a), and G4 (A5A4B3) glycinin and the
      alpha' subunit of beta-conglycinin in BSH-3 seeds. Despite the lack of these
      abundant seed proteins, BSH-3 seeds still accumulated 38% protein. BSH-3 seeds
      also accumulated high levels of free amino acids as compared with DN47 seeds,
      particularly arginine, and the amount of several essential amino acids were
      significantly elevated in BSH-3 seeds. Elevated accumulation of alpha and beta
      subunit of beta-conglycinin, G5 glycinin, Kunitz trypsin inhibitor, and Bowman
      Birk protease inhibitor indicates seed proteome rebalancing in BSH-3 seeds.
      Immunoblot analysis using sera from soybean allergic patients demonstrated the
      complete lack of a major allergen (alpha' subunit of beta-conglycinin) in BSH-3
      seeds. However, elevated levels of other allergens were found in BSH-3 seeds due
      to proteome rebalancing. Transmission electron microscopy observation of mature
      seeds of BSH-3 revealed striking differences in the appearance of the protein
      storage vacuoles when compared with DN47.

PMID- 29227097
TI  - Interfacial Antioxidants: A Review of Natural and Synthetic Emulsifiers and
      Coemulsifiers That Can Inhibit Lipid Oxidation.
AB  - There has been strong interest in developing effective strategies to inhibit
      lipid oxidation in emulsified food products due to the need to incorporate
      oxidatively labile bioactive lipids, such as omega-3 fatty acids, conjugated
      linoleic acids, or carotenoids. Emulsifiers or coemulsifiers can be utilized to
      inhibit lipid oxidation in emulsions. Both of these molecular types can adsorb to
      droplet surfaces and inhibit lipid oxidation, but emulsifiers can also stabilize
      droplets against aggregation whereas coemulsifiers cannot. There are a host of
      existing emulsifiers, covalent conjugates, or physical complexes that have the
      potential to inhibit lipid oxidation by a variety of mechanisms. Existing
      emulsifiers with antioxidant potential consist of surfactants, phospholipids,
      proteins, polysaccharides, and colloidal particles. Conjugates and complexes are
      typically formed by covalently or physically linking together a surface-active
      molecule with an antioxidant molecule. This article reviews the molecular and
      physicochemical basis for the surface and antioxidant activities of emulsifiers
      and coemulsifiers, highlights the important properties of interfacial layers that
      can be engineered to control lipid oxidation, and outlines different kinds of
      existing emulsifiers, conjugates, and complexes that can be used to inhibit
      oxidation.

PMID- 29227098
TI  - Energy Transfer Mechanisms and Optical Thermometry of BaMgF4:Yb3+,Er3+ Phosphor.
AB  - Motivated from our previous studies on the upconversion properties of
      BaMgF4:Yb3+,Tb3+ phosphor, here we investigated the upconversion properties of
      BaMgF4:Yb3+,Er3+ phosphor. We demonstrate a two-way versatile approach for the
      fine-tuning of emission from green to the red region, by varying the dopant
      concentration and adjusting the pulse width of an infrared laser. The mechanism
      involved in tuning the emission color by laser power and pulse width variation
      was illustrated in detail. The temperature dependent upconversion spectra were
      studied by analyzing the fluorescence intensity ratio of the thermally coupled
      levels. The maximum sensitivity obtained is 83.29 * 10-4 K-1 at 583 K, which is
      much higher than the temperature sensitivity reported for other fluoride based
      materials. Moreover, the influence of the excitation power density on the ability
      of the phosphor for temperature sensing was also investigated. We obtained a
      maximum (~415 K) temperature detection at 2563 mW laser power. The obtained
      results illustrate the potential use of BaMgF4:Yb3+,Er3+ phosphor in an optical
      thermometer due to its highly sensitive temperature detection ability.

PMID- 29227099
TI  - Activity of Icacinol from Icacina trichantha on Seedling Growth of Oryza sativa
      and Arabidopsis thaliana.
AB  - Broadleaf weeds are very costly for crop growers. Additional herbicidal compounds
      need to be obtained, especially from natural sources. Extracts of Icacina
      trichantha were evaluated for responses in germinating seeds and seedlings of
      rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana). An ethyl acetate
      fraction of I. trichantha tuber and a diterpenoid constituent, icacinol (1), were
      found to have impacts on germination and growth of seedlings. The seed
      germination inhibitory activity on rice was minimal, but significant on
      Arabidopsis. While rice indicated some growth delay in leaf expansion in the
      presence of 1, the effects appeared temporary; chlorophyll and anthocyanins were
      not significantly altered compared to DMSO controls. Rice seedlings attained
      biomass similar to DMSO controls, and rice grains per panicle were not
      significantly different from the DMSO controls. On the other hand, Arabidopsis
      exhibited damage to leaf expansion, reduced chlorophyll, and increased
      anthocyanins in aerial portions of the seedlings. Icacinol (1) may be a suitable
      chemical agent to investigate further for the treatment of eudicot weeds.

PMID- 29227100
TI  - Copper Complexes in the Promotion of Aldol Addition to Pyridine-2-carboxaldehyde:
      Synthesis of Homo- and Heteroleptic Complexes and Stereoselective Double Aldol
      Addition.
AB  - CuCl2.2H2O and Cu(ClO4)2.6H2O are able to promote aldol addition of pyridine-2
      carboxaldehyde (pyca) with acetone, acetophenone, or cyclohexenone under neutral
      and mild conditions. The general and simple one-pot procedure for the aldol
      addition to Cu(II) complexes accesses novel Cu complexes with a large variety of
      different structural motifs, from which the aldol-addition ligand can be
      liberated by treatment with NH3. Neutral heteroleptic complexes in which the
      ligand acts as bidentate, or homoleptic cationic complexes in which the ligand
      acts as tridentate can be obtained depending on the copper salt used. The key
      step in these reactions is the coordination of pyca to copper, which increases
      the electrophilic character of the aldehyde, with Cu(ClO4)2 leading to a higher
      degree of activation than CuCl2, as predicted by DFT calculations. A regio- and
      stereoselective double aldol addition of pyca in the reaction of Cu(ClO4)2.6H2O
      with acetone leads to the formation of a dimer copper complex in which the novel
      double aldol addition product acts as a pentadentate ligand. A possible mechanism
      is discussed. The work is supported by extensive crystallographic studies.

PMID- 29227101
TI  - The Magic of Crystal Structure-Based Inhibitor Optimization: Development of a
      Butyrylcholinesterase Inhibitor with Picomolar Affinity and in Vivo Activity.
AB  - The enzymatic activity of butyrylcholinesterase (BChE) in the brain increases
      with the progression of Alzheimer's disease, thus classifying BChE as a promising
      drug target in advanced Alzheimer's disease. We used structure-based drug
      discovery approaches to develop potent, selective, and reversible human BChE
      inhibitors. The most potent, compound 3, had a picomolar inhibition constant
      versus BChE due to strong cation-pi interactions, as revealed by the solved
      crystal structure of its complex with human BChE. Additionally, compound 3
      inhibits BChE ex vivo and is noncytotoxic. In vitro pharmacokinetic experiments
      show that compound 3 is highly protein bound, highly permeable, and metabolically
      stable. Finally, compound 3 crosses the blood-brain barrier, and it improves
      memory, cognitive functions, and learning abilities of mice in a scopolamine
      model of dementia. Compound 3 is thus a promising advanced lead compound for the
      development of drugs for alleviating symptoms of cholinergic hypofunction in
      patients with advanced Alzheimer's disease.

PMID- 29227102
TI  - Electronic Structure of Cobalt-Corrole-Pyridine Complexes: Noninnocent Five
      Coordinate Co(II) Corrole-Radical States.
AB  - Two sets of complexes of Co-triarylcorrole-bispyridine complexes, Co[TpXPC](py)2
      and Co[Br8TpXPC](py)2 have been synthesized, where TpXPC refers to a meso
      tris(para-X-phenyl)corrole ligand with X = CF3, H, Me, and OMe and Br8TpXPC to
      the corresponding beta-octabrominated ligand. The axial pyridines in these
      complexes were found to be labile and, in dilute solutions in dichloromethane,
      the complexes dissociate almost completely to the five-coordinate monopyridine
      complexes. Upon addition of a small quantity of pyridine, the complexes revert
      back to the six-coordinate forms. These transformations are accompanied by
      dramatic changes in color and optical spectra. 1H NMR spectroscopy and X-ray
      crystallography have confirmed that the bispyridine complexes are authentic low
      spin Co(III) species. Strong substituent effects on the Soret maxima and broken
      symmetry DFT calculations, however, indicate a CoII-corrole*2- formulation for
      the five-coordinate Co[TpXPC](py) series. The calculations implicate a Co(dz2)
      corrole("a2u") orbital interaction as responsible for the metal-ligand
      antiferromagnetic coupling that leads to the open-shell singlet ground state of
      these species. Furthermore, the calculations predict two low-energy S = 1
      intermediate-spin Co(III) states, a scenario that we have been able to
      experimentally corroborate with temperature-dependent EPR studies. Our findings
      add to the growing body of evidence for noninnocent electronic structures among
      first-row transition metal corrole derivatives.

PMID- 29227103
TI  - A Robust Molecular Network Motif for Period-Doubling Devices.
AB  - Life is sustained by a variety of cyclic processes such as cell division, muscle
      contraction, and neuron firing. The periodic signals powering these processes
      often direct a variety of other downstream systems, which operate at different
      time scales and must have the capacity to divide or multiply the period of the
      master clock. Period modulation is also an important challenge in synthetic
      molecular systems, where slow and fast components may have to be coordinated
      simultaneously by a single oscillator whose frequency is often difficult to tune.
      Circuits that can multiply the period of a clock signal (frequency dividers),
      such as binary counters and flip-flops, are commonly encountered in electronic
      systems, but design principles to obtain similar devices in biological systems
      are still unclear. We take inspiration from the architecture of electronic flip
      flops, and we propose to build biomolecular period-doubling networks by combining
      a bistable switch with negative feedback modules that preprocess the circuit
      inputs. We identify a network motif and we show it can be "realized" using
      different biomolecular components; two of the realizations we propose rely on
      transcriptional gene networks and one on nucleic acid strand displacement
      systems. We examine the capacity of each realization to perform period-doubling
      by studying how bistability of the motif is affected by the presence of the
      input; for this purpose, we employ mathematical tools from algebraic geometry
      that provide us with valuable insights on the input/output behavior as a function
      of the realization parameters. We show that transcriptional network realizations
      operate correctly also in a stochastic regime when processing oscillations from
      the repressilator, a canonical synthetic in vivo oscillator. Finally, we compare
      the performance of different realizations in a range of realistic parameters via
      numerical sensitivity analysis of the period-doubling region, computed with
      respect to the input period and amplitude. Our mathematical and computational
      analysis suggests that the motif we propose is generally robust with respect to
      specific implementation details: functionally equivalent circuits can be built as
      long as the species-interaction topology is respected. This indicates that
      experimental construction of the circuit is possible with a variety of components
      within the rapidly expanding libraries available in synthetic biology.

PMID- 29227104
TI  - X-ray Absorption Spectroscopy Combined with Time-Dependent Density Functional
      Theory Elucidates Differential Substitution Pathways of Au(I) and Au(III) with
      Zinc Fingers.
AB  - A combination of two elements' (Au, Zn) X-ray absorption spectroscopy (XAS) and
      time-dependent density functional theory (TD-DFT) allowed the elucidation of
      differential substitution pathways of Au(I) and Au(III) compounds reacting with
      biologically relevant zinc fingers (ZnFs). Gold L3-edge XAS probed the
      interaction of gold and the C-terminal Cys2HisCys finger of the HIV-1
      nucleocapsid protein NCp7, and the Cys2His2 human transcription factor Sp1. The
      use of model compounds helped assign oxidation states and the identity of the
      gold-bound ligands. The computational studies accurately reproduced the
      experimental XAS spectra and allowed the proposition of structural models for the
      interaction products at early time points. The direct electrophilic attack on the
      ZnF by the highly thiophilic Au(I) resulted in a linear P-Au-Cys coordination
      sphere after zinc ejection whereas for the Sp1, loss of PEt3 results in linear
      Cys-Au-Cys or Cys-Au-His arrangements. Reactions with Au(III) compounds, on the
      other hand, showed multiple binding modes. Prompt reaction between [AuCl(dien)]2+
      and [Au(dien)(DMAP)]3+ with Sp1 showed a partially reduced Au center and a final
      linear His-Au-His coordination. Differently, in the presence of NCp7,
      [AuCl(dien)]2+ readily reduces to Au(I) and changes from square-planar to linear
      geometry with Cys-Au-His coordination, while [Au(dien)(DMAP)]3+ initially
      maintains its Au(III) oxidation state and square-planar geometry and the same
      first coordination sphere. The latter is the first observation of a "noncovalent"
      interaction of a Au(III) complex with a zinc finger and confirms early hypotheses
      that stabilization of Au(III) occurs with N-donor ligands. Modification of the
      zinc coordination sphere, suggesting full or partial zinc ejection, is observed
      in all cases, and for [Au(dien)(DMAP)]3+ this represents a novel mechanism for
      nucleocapsid inactivation. The combination of XAS and TD-DFT presents the first
      direct experimental observation that not only compound reactivity, but also ZnF
      core specificity, can be modulated on the basis of the coordination sphere of
      Au(III) compounds.

PMID- 29227105
TI  - Correlation between Chemical and Physical Pressures on Charge Bistability in
      [Pd(en)2Br](Suc-Cn)2.H2O.
AB  - Hydrostatic (physical) pressure effects on the electrical resistivity of a
      bromido-bridged palladium compound, [Pd(en)2Br](Suc-C5)2.H2O, were studied. The
      charge-density-wave to Mott-Hubbard phase transition temperature (TPT) steadily
      increased with pressure. By a comparison of the effects of the chemical and
      physical pressures on TPT, it was estimated that the chemical pressure by unit
      alkyl chain length, i.e., the number of carbon atoms in the alkyl chains within
      the counterion, corresponded to ca. 1.3 kbar of the physical pressure.

PMID- 29227106
TI  - Hollow Silica Nanoparticles Penetrate the Peripheral Nerve and Enhance the Nerve
      Blockade from Tetrodotoxin.
AB  - The efficacy of tetrodotoxin (TTX), a very potent local anesthetic, is limited by
      its poor penetration through barriers to axonal surfaces. To address this issue,
      we encapsulated TTX in hollow silica nanoparticles (TTX-HSN) and injected them at
      the sciatic nerve in rats. TTX-HSN achieved an increased frequency of successful
      blocks, prolonged the duration of the block, and decreased the toxicity compared
      to free TTX. In animals injected with fluorescently labeled HSN, the imaging of
      frozen sections of nerve demonstrated that HSN could penetrate into nerve and
      that the penetrating ability of silica nanoparticles was highly size-dependent.
      These results demonstrated that HSN could deliver TTX into the nerve, enhancing
      efficacy while improving safety.

PMID- 29227107
TI  - Oil-in-Water Emulsions Stabilized by Acylglutamic Acid-Alkylamine Complexes as
      Noncovalent-Type Double-Chain Amphiphiles.
AB  - We have studied the preparation and stabilization mechanism of oil-in-water-type
      emulsions in the presence of amphiphilic 1:1 stoichiometric complexes of
      acylglutamic acids (CnGlu) with tertiary alkylamines (CnDMA). Relatively stable
      emulsions were obtained when C16Glu-C16DMA (or C18Glu-C18DMA), hexadecane, and
      water were homogenized at 80  degrees C and then stored at room temperature. The
      gel-liquid crystal phase transition temperatures (Tc) of C16Glu-C16DMA and C18Glu
      C18DMA dispersed in water were determined to be ca. 39 and 53  degrees C,
      respectively. This indicates that the complexes form an adsorbed layer at the
      oil/water interface during the homogenization process above the Tc and then
      change into a gel during storage at room temperature. The gel phase formed at the
      oil/water interface prevents the oil droplets from coalescing. In contrast,
      shorter chain analogues (C10Glu-C10DMA and C12Glu-C12DMA) did not yield stable
      emulsions because their adsorption layers were not able to prevent coalescence of
      the oil droplets (i.e., the Tc of these analogues was below the room
      temperature). We have also demonstrated that the dispersion stability of these
      emulsion systems can be controlled by changing the aqueous pH.

PMID- 29227108
TI  - Visualizing Single-Cell Secretion Dynamics with Single-Protein Sensitivity.
AB  - Cellular secretion of proteins into the extracellular environment is an essential
      mediator of critical biological mechanisms, including cell-to-cell communication,
      immunological response, targeted delivery, and differentiation. Here, we report a
      novel methodology that allows for the real-time detection and imaging of single
      unlabeled proteins that are secreted from individual living cells. This is
      accomplished via interferometric detection of scattered light (iSCAT) and is
      demonstrated with Laz388 cells, an Epstein-Barr virus (EBV)-transformed B cell
      line. We find that single Laz388 cells actively secrete IgG antibodies at a rate
      of the order of 100 molecules per second. Intriguingly, we also find that other
      proteins and particles spanning ca. 100 kDa-1 MDa are secreted from the Laz388
      cells in tandem with IgG antibody release, likely arising from EBV-related viral
      proteins. The technique is general and, as we show, can also be applied to
      studying the lysate of a single cell. Our results establish label-free iSCAT
      imaging as a powerful tool for studying the real-time exchange between cells and
      their immediate environment with single-protein sensitivity.

PMID- 29227109
TI  - Fast and Environmentally Friendly Microfluidic Technique for the Fabrication of
      Polymer Microspheres.
AB  - This paper reports on a novel microfluidic technique for the fabrication of
      microspheres of synthetic polymers including poly(vinyl chloride) (PVC),
      poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), poly(lactic acid)
      (PLA), and polystyrene (PS). The polymers are dissolved in tetrahydrofuran (THF)
      and the method is based on the diminished solubility of THF in a 20% (w/v) NaCl
      solution which allows the formation of droplets of the polymer solution. These
      polymer solution droplets are generated in a microfluidic system and their
      desolvation is accomplished within seconds by allowing the droplets to rise by
      buoyancy through a NaCl solution with a concentration lower than 15%. The size
      and morphology of the resultant polymer microspheres have been investigated by
      optical and scanning electron microscopy. Apart from the elimination of the use
      of highly toxic solvents as in conventional methods for manufacturing of polymer
      microspheres, the newly developed technique has the advantages of providing
      faster desolvation of the polymer solution droplets and a higher yield of
      microspheres compared to emulsification-based techniques.

PMID- 29227111
TI  - Key Factors in Prevention of Peri-implant Diseases.
AB  - Prevention and treatment of peri-implant diseases have become a key element in
      modern implant dentistry. The long-term success of implantsupported restorations
      is not only dependent on the quality and precision of modern implant systems, but
      on the efficacy of preventive measures for thelong-term maintenance of peri
      implant tissues.

PMID- 29227110
TI  - iTRAQ Quantitative Proteomic Profiling and MALDI-MSI of Colon Cancer Spheroids
      Treated with Combination Chemotherapies in a 3D Printed Fluidic Device.
AB  - For a patient with metastatic colorectal cancer there are limited clinical
      options aside from chemotherapy. Unfortunately, the development of new
      chemotherapeutics is a long and costly process. New methods are needed to
      identify promising drug candidates earlier in the drug development process. Most
      chemotherapies are administered to patients in combinations. Here, an in vitro
      platform is used to assess the penetration and metabolism of combination
      chemotherapies in three-dimensional colon cancer cell cultures, or spheroids.
      Colon carcinoma HCT 116 cells were cultured and grown into three-dimensional cell
      culture spheroids. These spheroids were then dosed with a common combination
      chemotherapy, FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) in a 3D
      printed fluidic device. This fluidic device allows for the dynamic treatment of
      spheroids across a semipermeable membrane. Following dosing, the spheroids were
      harvested for quantitative proteomic profiling to examine the effects of the
      combination chemotherapy on the colon cancer cells. Spheroids were also imaged to
      assess the spatial distribution of administered chemotherapeutics and metabolites
      with MALDI-imaging mass spectrometry. Following treatment, we observed
      penetration of folinic acid to the core of spheroids and metabolism of the drug
      in the outer proliferating region of the spheroid. Proteomic changes identified
      included an enrichment of several cancer-associated pathways. This innovative
      dosing device, along with the proteomic evaluation with iTRAQ-MS/MS, provides a
      robust platform that could have a transformative impact on the preclinical
      evaluation of drug candidates. This system is a high-throughput and cost
      effective approach to examine novel drugs and drug combinations prior to animal
      testing.

PMID- 29227112
TI  - Clinical Management of Patients With Diabetes and Periodontal Disease: Ideas
      Whose Time Has Come.
AB  - Multiple studies over many decades have demonstrated that diabetes mellitus and
      periodontitis are closely linked and may amplify one another. This review
      provides a different look at the complex association between these two common,
      chronic conditions and discusses decision-making in the management of affected
      individuals.

PMID- 29227113
TI  - The Microbiome of Peri-implantitis: Is It Unique?
AB  - A better characterization of the peri-implant microbiome can improve the
      understanding of the etiology of peri-implant diseases. Ultimately, more detailed
      information about the peri-implantitis microbiome will lead to better strategies
      for prevention, supportive therapy, and risk assessment, as well as early
      diagnosis of peri-implantitis and timely intervention, all of which are critical
      for the long-term retention of implants.

PMID- 29227114
TI  - A Role for Oral Health Personnel in Stroke Prevention.
AB  - Possible links between stroke and periodontal disease are reviewed in this
      article. Topics covered include the signs and symptoms of stroke, dental and
      other infections associated with stroke, and the role of oral healthcare
      personnel in the prevention of stroke and treatment of stroke patients.

PMID- 29227115
TI  - Fundamentals of Precision Medicine.
AB  - Precision medicine is no longer a distant vision; it is becoming part of the
      rapidly evolving present. Insights from studies of the human genome and
      microbiome, their associated transcriptomes, proteomes, and metabolomes, and
      epigenomics and exposomics have reached an unprecedented depth and scale. Much
      more needs to be done, however, particularly in dentistry.

PMID- 29227116
TI  - Periodontal Diagnosis and Treatment in the Coming Decades.
AB  - The purpose of this article is to review the dominant paradigms and thinking
      behind periodontal diagnosis and treatment over the last 150 years, including the
      clinical characteristics paradigm, the classical pathology paradigm, and the
      infection/ host response paradigm, and to predict what changes may occur in the
      next 50 years, such as the molecular ecology paradigm.

PMID- 29227117
TI  - An autopsy case of death by combined use of benzodiazepines and diphenidine.
AB  - We present an autopsy case involving benzodiazepines and diphenidine.
      Quantitative toxicological analysis showed concentrations of 7-aminoflunitrazepam
      (a flunitrazepam metabolite), 7-aminonimetazepam (a nimetazepam metabolite),
      chlorpheniramine and diphenidine in femoral blood of 0.086 ug/ml, 0.027 ug/ml,
      0.066 ug/ml, and 0.073 ug/ml, respectively. Death was attributed to combined
      toxicity due to the influence of multiple drug interactions.

PMID- 29227118
TI  - Complex suicide involving pyrethroid ingestion (mosquito coils) and fatal self
      wounding by sharp force.
AB  - "Complex suicide" is a term referring to the suicidal pattern in which more than
      one suicidal method is applied in the purpose of inducing death. The present
      paper aims to review complex suicide literature shortly and investigate an
      unusual planned complex suicide incident, the rarity of which is attributable to
      the combination of suicide methods as well as the type and quantity of substances
      applied to induce poisoning. A 33-year-old man with a history of psychotic
      depression was found dead in his bedroom lying within a large quantity of blood.
      He had already committed two previous suicide attempts and he was under treatment
      with antidepressants. The forensic examination revealed the use of the following
      successive suicide methods: benzodiazepine and alcohol intake, pyrethroid
      poisoning due to ingestion of mosquito coils, wrist cutting, and a fatal cut in
      the victims neck. Death occurred due to hemorrhagic shock. Furthermore, the
      authors extensively discuss the use of sharp force in suicide and the
      discrimination "tools" between suicide and homicide.

PMID- 29227119
TI  - [Molecular pathology of lung cancer in routine diagnostic practice: 2017 update].
AB  - The group of non-small cell lung carcinomas includes tumors that are variable at
      the clinical, histopathological and molecular levels. Advances in the
      understanding of molecular pathology of lung adenocarcinomas in particular led to
      changes in their histopathological classification and treatment. Patients
      diagnosed with lung adenocarcinoma harboring specific mutations benefit from the
      administration of specific targeted therapy. Analysis of EGFR gene mutations and
      ALK rearrangement in lung adenocarcinomas are already routinely performed and are
      closely related to the indication for the administration of tyrosinkinase
      inhibitors. Besides EGFR mutations and ALK rearrangement there are also available
      other potential markers for analyzing, e.g. b-raf - BRAF, ROS1. Moreover,
      immunotherapy needs standardization of detection of crucial molecules, namely PD
      L1. The aim of this review is to summarize the role of the most relevant
      molecules that could also serve as the therapeutic target for practicing
      pathologists.

PMID- 29227120
TI  - [Molecular mechanisms of primary and secondary resistance, molecular-genetic
      features and characteristics of KIT/PDGFRA non-mutated GISTs].
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. Most of them arise due to activating mutations in KIT
      (75 - 85 %) or PDGFRA (less than 10 %) genes. Identification of the activating
      mutations in KIT and PDGFRA genes, which code for receptor tyrosine kinases
      (RTKs), has improved the outcome of targeted therapy of metastatic, unresectable
      or recurrent GISTs. Primary and/or secondary resistance represents a significant
      problem in the targeted therapy by Imatinib mesylate (IM) in patients with GIST.
      An important mechanism of the secondary resistance is the evolvement of secondary
      mutations. Except for primary and secondary resistance, there is another problem
      of disease progression - a failure of tumor cells eradication even in the long
      term therapy of tyrosine kinase inhibitors. GISTs without mutations in KIT/PDGFRA
      genes constitute 10 - 15% GISTs in adults, and a majority (85 %) of pediatric
      GISTs. KIT/PDGFRA wild-type GISTs represent a heterogeneous group of tumors with
      several molecular-genetics and/or morphologic differences. KIT/PDGFRA wild-type
      GISTs are different in their molecular features, for example in mutations in the
      BRAF, KRAS, NF1 genes or defects of succinate dehydrogenase (SDH) subunits.
      KIT/PDGFRA wild-type GISTs are generally less sensitive to targeted therapy by
      tyrosine kinase inhibitors in comparison with KIT/PDGFRA mutated GISTs.
      Inhibitors of BRAF, PI3K (mTOR) or inhibitors of IGF1R and VEGFR receptors
      provide alternative therapeutic strategies.

PMID- 29227121
TI  - [What's new in Ewing-like sarcoma family? Soft tissue and bone sarcomas with
      CIC/BCOR rearrangement. Review of the literature and first personal experience].
AB  - The literature is reviewed regarding of a rare molecularly defined group of
      sarcomas with rearrangement of both CIC and BCOR genes, which were originally
      placed into the EWSR1wt Ewing-like category. Personal experience with three cases
      demonstrating difficulties of this issue is added. Both groups of lesions differ
      not only by age and topography, but also vary in both the prognostic and the
      predictive parameters. CIC-rearranged tumors are very aggressive and almost never
      occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly
      bone tumors in young males behaving even better than classical Ewing sarcoma.
      From the morphologic point of view, it turned out to be a salient finding that
      these types of neoplasm might leave canonical morphotype of small blue round cell
      sarcoma. Instead of it, they are not uncommonly characterized as a relatively
      uniform spindle cell proliferation with prevailing myxoid transformation
      deserving much broader differential diagnosis. Our three cases reports display
      difficulties in reaching the correct diagnosis even by implementing sophisticated
      molecular techniques in routine practice. Notwithstanding of exhaustive molecular
      assays used, one may still encounter a lesion where original descriptive term
      Ewing-lie sarcoma remains uncorrected.

PMID- 29227122
TI  - [Hamartoma of mature cardiac myocytes. Autopsy case report].
AB  - Hamartoma of mature cardiac myocytes (HMCM) is a rare benign pseudoneoplastic
      myocardial lesion. We describe a case of 39-year-old Bulgarian woman living in
      the Czech Republic, who died because of rupture of anterior communicating artery
      aneurysm, and severe bronchopneumonia. An incidental finding at the autopsy was a
      whitish unencapsulated and not sharply demarcated tumor of the left ventricle and
      adjacent area of interventricular septum, which protruded above the plane of
      section. Microscopically the tumor consisted of various different forms of
      disorganized hypertrophic mature cardiac myocytes without vacuolization of
      cytoplasm, focally in a "herringbone" pattern. Dilated venules and thickened
      intramural coronary arteries, and intervening bands of connective tissue were
      present between cardiomyocytes in the tumor. Immunohistochemical staining of MIB1
      for the detection of proliferative activity was completely negative. No
      inflammatory infiltration, adipose tissue or calcifications were present in the
      tumor.

PMID- 29227123
TI  - The importance of assessing for validity of symptom report and performance in
      attention deficit/hyperactivity disorder (ADHD): Introduction to the special
      section on noncredible presentation in ADHD.
AB  - Invalid self-report and invalid performance occur with high base rates in
      attention deficit/hyperactivity disorder (ADHD; Harrison, 2006; Musso & Gouvier,
      2014). Although much research has focused on the development and validation of
      symptom validity tests (SVTs) and performance validity tests (PVTs) for
      psychiatric and neurological presentations, less attention has been given to the
      use of SVTs and PVTs in ADHD evaluation. This introduction to the special section
      describes a series of studies examining the use of SVTs and PVTs in adult ADHD
      evaluation. We present the series of studies in the context of prior research on
      noncredible presentation and call for future research using improved research
      methods and with a focus on assessment issues specific to ADHD evaluation.
      (PsycINFO Database Record

PMID- 29227124
TI  - The effects of symptom information coaching on the feigning of adult ADHD.
AB  - College students without ADHD may feign symptoms of ADHD to gain access to
      stimulant medications and academic accommodations. Unfortunately, research has
      shown that it can be difficult to discriminate malingered from genuine ADHD
      symptomatology, especially when evaluations are based only on self-report
      questionnaires. The present study investigated whether nonclinical college
      students given no additional information could feign ADHD as successfully as
      those who were coached on symptoms of the disorder. Similar to Jasinski et al.
      (2011) and other research on feigned ADHD, a battery of neuropsychological,
      performance validity, and self-report tests was administered. Undergraduates with
      no history of ADHD or other psychiatric disorders were randomly assigned to 1 of
      2 simulator groups: a coached group that was given information about ADHD
      symptoms, or a noncoached group that was given no such information. Both
      simulator groups were asked to feign ADHD. Their performance was compared to a
      genuine ADHD group and a nonclinical group asked to respond honestly. Self
      report, neuropsychological, and performance validity test data are discussed in
      the context of the effect of coaching and its implications for ADHD evaluations.
      Symptom coaching did not have a significant effect on feigning success.
      Performance validity tests were moderately effective at detecting feigned ADHD.
      (PsycINFO Database Record

PMID- 29227125
TI  - Utility of the Conners' Adult ADHD Rating Scale validity scales in identifying
      simulated attention-deficit hyperactivity disorder and random responding.
AB  - Recent concern about malingered self-report of symptoms of attention-deficit
      hyperactivity disorder (ADHD) in college students has resulted in an urgent need
      for scales that can detect feigning of this disorder. The present study provided
      further validation data for a recently developed validity scale for the Conners'
      Adult ADHD Rating Scale (CAARS), the CAARS Infrequency Index (CII), as well as
      for the Inconsistency Index (INC). The sample included 139 undergraduate
      students: 21 individuals with diagnoses of ADHD, 29 individuals responding
      honestly, 54 individuals responding randomly (full or half), and 35 individuals
      instructed to feign. Overall, the INC showed moderate sensitivity to random
      responding (.44-.63) and fairly high specificity to ADHD (.86-.91). The CII
      demonstrated modest sensitivity to feigning (.31-.46) and excellent specificity
      to ADHD (.91-.95). Sequential application of validity scales had correct
      classification rates of honest (93.1%), ADHD (81.0%), feigning (57.1%), half
      random (42.3%), and full random (92.9%). The present study suggests that the CII
      is modestly sensitive (true positive rate) to feigned ADHD symptoms, and highly
      specific (true negative rate) to ADHD. Additionally, this study highlights the
      utility of applying the CAARS validity scales in a sequential manner for
      identifying feigning. (PsycINFO Database Record

PMID- 29227126
TI  - Intentional inattention: Detecting feigned attention-deficit/hyperactivity
      disorder on the Personality Assessment Inventory.
AB  - Given the increasing number of college students seeking Attention
      Deficit/Hyperactivity Disorder (ADHD) diagnoses as well as the potential
      secondary gains associated with this disorder (e.g., access to stimulant
      medication, academic accommodations), the detection of malingered symptom
      presentations in this population is a major concern. The present study examined
      the ability of validity indicators on the widely used Personality Assessment
      Inventory (PAI; Morey, 1991) to distinguish between individuals experiencing
      genuine ADHD symptoms and individuals instructed to present with ADHD
      symptomatology for secondary gain. Sixty-six participants who successfully
      simulated ADHD (based on elevations on the Conners' Adult ADHD Rating Scale;
      Conners, Erhardt, & Sparrow, 1998) were compared with a sample of undergraduate
      students meeting diagnostic criteria for ADHD (N = 22) and an archival sample of
      adults who received an ADHD diagnosis at a university psychology clinic following
      a comprehensive psychological evaluation (N = 41). Successful simulators obtained
      significantly higher scores on all relevant PAI validity indicators compared with
      the clinical and archival comparison samples, with the Rogers Discriminant
      Function demonstrating the highest predictive accuracy (AUC = .86). Traditional
      cut scores on the Negative Impression (NIM) validity scale used to designate
      probable malingering, however, were not sensitive to simulated ADHD symptoms,
      although they did demonstrate excellent specificity. The PAI may be informative
      as an indicator of potentially exaggerated or malingered symptom presentation,
      but alternative cut scores for symptom validity indicators may be necessary to
      maximize its utility in these particular types of psychological evaluations.
      (PsycINFO Database Record

PMID- 29227127
TI  - Symptom and performance validity with veterans assessed for attention
      deficit/hyperactivity disorder (ADHD).
AB  - Little is known about attention-deficit/hyperactivity disorder (ADHD) in
      veterans. Practice standards recommend the use of both symptom and performance
      validity measures in any assessment, and there are salient external incentives
      associated with ADHD evaluation (stimulant medication access and academic
      accommodations). The purpose of this study was to evaluate symptom and
      performance validity measures in a clinical sample of veterans presenting for
      specialty ADHD evaluation. Patients without a history of a neurocognitive
      disorder and for whom data were available on all measures (n = 114) completed a
      clinical interview structured on DSM-5 ADHD symptoms, the Minnesota Multiphasic
      Personality Inventory-2-Restructured Form (MMPI-2-RF), and the Test of Memory
      Malingering Trial 1 (TOMM1) as part of a standardized ADHD diagnostic evaluation.
      Veterans meeting criteria for ADHD were not more likely to overreport symptoms on
      the MMPI-2-RF nor to fail TOMM1 (score <= 41) compared with those who did not
      meet criteria. Those who overreported symptoms did not endorse significantly more
      ADHD symptoms; however, those who failed TOMM1 did report significantly more ADHD
      symptoms (g = 0.90). In the total sample, 19.3% failed TOMM1, 44.7% overreported
      on the MMPI-2-RF, and 8.8% produced both an overreported MMPI-2-RF and invalid
      TOMM1. F-r had the highest correlation to TOMM1 scores (r = -.30). These results
      underscore the importance of assessing both symptom and performance validity in a
      clinical ADHD evaluation with veterans. In contrast to certain other conditions
      (e.g., mild traumatic brain injury), ADHD as a diagnosis is not related to higher
      rates of invalid report/performance in veterans. (PsycINFO Database Record

PMID- 29227128
TI  - Noncredible cognitive performance at clinical evaluation of adult ADHD: An
      embedded validity indicator in a visuospatial working memory test.
AB  - The assessment of performance validity is an essential part of the
      neuropsychological evaluation of adults with attention-deficit/hyperactivity
      disorder (ADHD). Most available tools, however, are inaccurate regarding the
      identification of noncredible performance. This study describes the development
      of a visuospatial working memory test, including a validity indicator for
      noncredible cognitive performance of adults with ADHD. Visuospatial working
      memory of adults with ADHD (n = 48) was first compared to the test performance of
      healthy individuals (n = 48). Furthermore, a simulation design was performed
      including 252 individuals who were randomly assigned to either a control group (n
      = 48) or to 1 of 3 simulation groups who were requested to feign ADHD (n = 204).
      Additional samples of 27 adults with ADHD and 69 instructed simulators were
      included to cross-validate findings from the first samples. Adults with ADHD
      showed impaired visuospatial working memory performance of medium size as
      compared to healthy individuals. Simulation groups committed significantly more
      errors and had shorter response times as compared to patients with ADHD.
      Moreover, binary logistic regression analysis was carried out to derive a
      validity index that optimally differentiates between true and feigned ADHD. ROC
      analysis demonstrated high classification rates of the validity index, as shown
      in excellent specificity (95.8%) and adequate sensitivity (60.3%). The
      visuospatial working memory test as presented in this study therefore appears
      sensitive in indicating cognitive impairment of adults with ADHD. Furthermore,
      the embedded validity index revealed promising results concerning the detection
      of noncredible cognitive performance of adults with ADHD. (PsycINFO Database
      Record

PMID- 29227129
TI  - Assessment of a portable lactate meter for field use in the white rhinoceros
      (<i>Ceratotherium simum</i>).
AB  - Blood lactate is a predictor of mortality in critically ill humans and animals.
      Handheld lactate meters have the potential to be used in the field to evaluate
      the condition of severely injured rhinoceroses but have not been compared with
      laboratory-based methods. Agreement between a handheld lactate meter and a
      laboratory method was assessed, as was the stability of rhino blood lactate in
      the anticoagulant sodium fluoride/potassium oxalate (fluoride/oxalate). Blood
      samples were obtained from 53 white rhinos that had been immobilised for
      management reasons. Lactate was measured by means of a handheld meter using whole
      blood in heparin (WBHEP), whole blood in fluoride/oxalate (WBFO) and
      fluoride/oxalate plasma (PFO). Results were recorded in both blood (BL) and
      plasma (PL) modes and compared to an established laboratory method for measuring
      plasma lactate. To assess the stability of lactate over time, blood lactate in
      fluoride/oxalate was measured on the handheld meter at intervals for up to 91 h.
      Agreement was best using WBFO in PL mode, with small bias (-0.16), tight 95%
      limits of agreement (LOA) (-1.46, 1.14) and a Pc (95% CI) of 0.97 (0.92, 0.99).
      The agreement was improved for all sample types when using the PL mode compared
      to the blood lactate (BL) mode. Blood lactate was stable in fluoride/oxalate for
      91 h, with a mean change from baseline of 0.15 (-0.178, 0.478) mmol/L (mean, 95%
      CI). The handheld meter was found to be suitable for field use in white rhinos
      but provided more reliable results with the device in PL mode. Furthermore, rhino
      blood lactate was found to be stable in fluoride/oxalate for as long as 3 days.

PMID- 29227130
TI  - Investigation of the acaricidal activity of the acetone and ethanol extracts of
      12 South African plants against the adult ticks of <i>Rhipicephalus
      turanicus</i>.
AB  - The acaricidal activity of acetone and ethanol extracts of 12 plant species was
      evaluated using the contact method on Rhipicephalus turanicus (Acari: Ixodidae)
      ticks at an initial concentration of 20% (200 mg/mL). Eight of the 12 plants had
      mortality greater than 50% and the acetone extracts had better acaricidal
      activity than the ethanol extracts. The acetone extract of Calpurnia aurea
      (leaves and flowers) had the highest corrected mortality (CM) of 92.2% followed
      by Schkuhria pinnata (whole plant) with a CM of 88.9%, Ficus sycomorus (bark and
      stems) 86.7% and Senna italica subsp. arachoides (roots, leaves and fruits)
      83.3%. Selected extracts were tested at five different concentrations using the
      adult immersion test. From dose-response assays, EC<sub>50</sub> values of 61.82
      mg/mL, 115.21 mg/mL and 161.02 mg/mL were obtained for the acetone extracts of S.
      pinnata (whole plant), S. italica subsp. arachoides (roots, leaves and fruits)
      and C. aurea (leaves and flowers) respectively. The ethanol extract of Monsonia
      angustifolia (whole plant) had the highest CM of 97.8% followed by S. pinnata
      (whole plant) with a CM of 86.7%, C. aurea (leaves and flowers) 81.1% and Cleome
      gynandra (leaves) 77.8%. There is potential for the development of
      environmentally benign botanicals as natural acaricides against R. turanicus.

PMID- 29227131
TI  - A serosurvey of bluetongue and epizootic haemorrhagic disease in a convenience
      sample of sheep and cattle herds in Zimbabwe.
AB  - A convenience sample of sheep and cattle herds around the cities of Harare,
      Kwekwe and Bulawayo, located in the Highveld region of Zimbabwe, was used to
      estimate the seroprevalence and sero-incidence of bluetongue virus (BTV) and
      epizootic haemorrhagic disease virus (EHDV) antibodies. A competitive enzyme
      linked immunosorbent assay was used to identify serum antibodies against BTV and
      EHDV across three rainy seasons. The median sero-prevalence of BTV and EHDV
      antibodies in cattle was 62% (interquartile range [IQR]: 30-89) and 56% (IQR: 5
      77), respectively. In sheep, the median sero-prevalence of BTV and EHDV was 41%
      (IQR: 19-63) and 0% (IQR: 0-21), respectively. Median sero-incidences of BTV and
      EHDV antibodies in cattle of 43% (IQR: 22-67) and 27% (IQR: 9-57) respectively
      were recorded. The median sero-incidence of BTV in sheep was 14% (IQR: 6-23).
      Based on these preliminary findings, animal health workers in Zimbabwe should
      continue to monitor the exposure rates of cattle and sheep to BTV and consider
      the possibility of strains emerging with increased pathogenicity. There are no
      previous published reports of antibodies against EHDV in Zimbabwe so the
      possibility of epizootic haemorrhagic disease existing in domestic livestock
      should now be considered by Zimbabwean animal health officials. Seroconversions
      to BTV and EHDV occurred predominantly at the end of each rainy season (March and
      April), which generally corresponds to high numbers of the Culicoides vectors.
      BTV isolations were made from three individual cows in two of the sentinel herds
      and all three were identified as serotype 3. This is the first time BTV serotype
      3 has been recorded in Zimbabwe, although its presence in neighbouring South
      Africa is well documented.

PMID- 29227132
TI  - Mental illness in Bwindi, Uganda: Understanding stakeholder perceptions of
      benefits and barriers to developing a community-based mental health programme.
AB  - BACKGROUND: Mental illness has been increasingly recognised as a source of
      morbidity in low- and middle-income countries and significant treatment gaps
      exist worldwide. Studies have demonstrated the effectiveness of task sharing
      through community-based treatment models for addressing international mental
      health issues. AIM: This paper aims to evaluate the perceptions of a wide range
      of mental health stakeholders in a Ugandan community regarding the benefits and
      barriers to developing a community-based mental health programme. SETTING: Bwindi
      Community Hospital (BCH) in south-west Uganda provides services through a team of
      community health workers to people in the Kanungu District. METHODS: Thematic
      analysis of 13 semi-structured interviews and 6 focus group discussions involving
      54 community members and 13 mental health stakeholders within the BCH catchment
      area. RESULTS: Stakeholders perceived benefits to a community-based compared to a
      hospital-based programme, including improved patient care, lower costs to
      patients and improved community understanding of mental illness. They also cited
      barriers including cost, insufficient workforce and a lack of community
      readiness. CONCLUSIONS: Stakeholders express interest in developing community
      based mental health programmes, as they feel that it will address mental health
      needs in the community and improve community awareness of mental illness.
      However, they also report that cost is a significant barrier to programme
      development that will have to be addressed prior to being able to successfully
      establish such programming. Additionally, many community members expressed unique
      sociocultural beliefs regarding the nature of mental illness and those suffering
      from a psychiatric disease.

PMID- 29227133
TI  - Prevalence of intimate partner violence and associated factors amongst women
      attending antenatal care at Outapi clinic, Namibia: A descriptive survey.
AB  - BACKGROUND: Intimate partner violence (IPV) is a significant and largely hidden
      public health problem for all women and, during pregnancy, can have significant
      effects on the health of both mother and the unborn baby. Previous Namibian
      studies suggest rates of IPV as high as 36%, although few studies have been
      conducted in primary care. AIM: To determine the prevalence of IPV amongst women
      attending antenatal care. SETTING: Outapi primary care clinic, Namibia. METHODS:
      A descriptive survey administering a validated questionnaire to 386 consecutive
      participants. RESULTS: The mean age of the participants was 27.5 years (standard
      deviation = 6.8), 335 (86.8%) were unmarried, 215 (55.7%) had only primary school
      education and 237 (61.4%) were in their third trimester. Overall, 51 participants
      (13.2%) had HIV and 44 (11.4%) had teenage pregnancies. The reported lifetime
      prevalence of IPV was 39 (10.1%), the 12-month prevalence was 35 (9.1%) and the
      prevalence during pregnancy was 31 (8.0%). Emotional abuse was the commonest type
      of abuse in 27 (7.0%). The commonest specific abusive behaviour was refusing to
      provide money to run the house or look after the children whilst the partner
      spent money on his priorities (4.9%). Increased maternal age was associated with
      an increase in the occurrence of IPV. CONCLUSION: The reported lifetime
      prevalence of IPV was 10.1%, with emotional abuse being the commonest type of
      abuse. Increased age was associated with an increase in reported IPV. IPV is
      significant enough to warrant that healthcare providers develop guidelines to
      assist women affected by IPV in Namibia.

PMID- 29227134
TI  - Evaluating the effect of the Practical Approach to Care Kit on teaching medical
      students primary care: Quasi-experimental study.
AB  - BACKGROUND: South Africa is committed to health reforms that strengthen primary
      health care. Preparing future doctors to work in primary care teams with other
      professionals is a priority, and medical schools have shifted towards community
      based and decentralised training of medical students. AIM: To evaluate the effect
      on student performance of the Practical Approach to Care Kit (PACK) (an
      integrated decision-making tool for adult primary care) during the final phase of
      medical student training at Stellenbosch University. SETTING: Clinical rotations
      in family medicine at clinics in the Western Cape. METHODS: Mixed methods
      involving a quasi-experimental study and focus group interviews. Student
      examination performance was compared between groups with and without exposure to
      the PACK during their clinical training. Student groups exposed to PACK were
      interviewed at the end of their rotations. RESULTS: Student performance in
      examinations was significantly better in those exposed to the PACK. Students
      varied from using the PACK overtly or covertly during the consultation to
      checking up on decisions made after the consultation. Some felt that the PACK was
      more suitable for nurses or more junior students. Although tutors openly endorsed
      PACK, very few modelled the use of PACK in their clinical practice. CONCLUSION:
      The use of PACK in the final phase of undergraduate medical education improved
      their performance in primary care. Students might be more accepting and find the
      tool more useful in the earlier clinical rotations. Supervisors should be trained
      further in how to incorporate the use of the PACK in their practice and
      educational conversations.

PMID- 29227135
TI  - We can make it happen.
AB  - No abstract available.

PMID- 29227136
TI  - Facilitators and barriers to effective primary health care in Zimbabwe.
AB  - No abstract available.

PMID- 29227137
TI  - Corrigendum: The effectiveness of the South African Triage Tool use in Mahalapye
      District Hospital - Emergency Department, Botswana.
AB  - No abstract available.

PMID- 29227138
TI  - A comparison of mycotoxin contamination of premium and grocery brands of pelleted
      cat food in South Africa.
AB  - Contamination with mycotoxins is of concern to pet owners and veterinary
      practitioners owing to their ability to cause disease and exacerbate the
      pathological changes associated with other diseases. Currently, there is a lack
      of information regarding the mycotoxin content of common premium brand (PB) and
      grocery brand (GB) cat feeds. Therefore, we undertook to determine the mycobiota
      content of feed samples, from both categories (n = 6 each), and measured the
      levels of aflatoxin (AF), fumonisin (FB), ochratoxin A (OTA) and zearalenone
      (ZEA) by high performance liquid chromatographic analysis. There were high
      concentrations of mycotoxins in both categories of feed, regardless of the notion
      that PBs are of a higher quality. The concentration of these toxins may
      contribute to the development of related pathologies in felines.

PMID- 29227139
TI  - Phenotypic hip and elbow dysplasia trends in Rottweilers and Labrador retrievers
      in South Africa (2007-2015): Are we making progress?
AB  - Canine hip and elbow dysplasia are major orthopaedic problems prevalent the world
      over, and South Africa is no exception. Hip and elbow dysplasia phenotypic status
      is certified by a number of different radiographic schemes in the world. South
      Africa uses the Federation Cynologique Internationale system to certify hips, and
      the International Elbow Working Group scheme to certify elbows. One way of
      reducing these often crippling conditions is by selective breeding using only
      dogs with no or marginal dysplastic joints. In South Africa, only seven breeds,
      including the Rottweiler, have breeding restrictions for hip dysplasia. There are
      no such restrictions for elbow dysplasia. This study assessed the prevalence of
      hip and elbow dysplasia over a 9-year-period in the Rottweiler and the Labrador
      retriever in South Africa as evaluated by official national scrutineers. Records
      from 1148 Rottweilers and 909 Labrador retrievers were obtained and were graded
      as normal or dysplastic, and numerical values were also evaluated. Data were
      compared between the two breeds, males and females as well as over time and were
      compared with similar data of the Orthopaedic Foundation for Animals in the
      United States. The prevalence values for hip dysplasia in Rottweilers and
      Labrador retrievers were 22% and 31%, respectively, whereas for elbow dysplasia
      the values were 39% and 19%, respectively. In Labrador retrievers, this incidence
      was much higher than in the American population. Rottweiler hip and elbow
      dysplasia numerical scores significantly improved over time, whereas in Labrador
      retrievers, only hip dysplasia showed a minor but significant improvement. This
      study proved that prescribing minimum breeding requirements, as in the Rottweiler
      in this study, significantly improved the breeding stock, suggesting that minimum
      hip and elbow breeding requirements should be initiated for all breeds at risk of
      these often crippling conditions.

PMID- 29227140
TI  - Range expansion of the economically important Asiatic blue tick, <i>Rhipicephalus
      microplus</i>, in South Africa.
AB  - The Asiatic blue tick, Rhipicephalus microplus, a known vector of bovine
      babesiosis and bovine anaplasmosis, is of great concern in the cattle industry.
      For this reason, detailed knowledge of the distribution of R. microplus is vital.
      Currently, R. microplus is believed to be associated mainly with the northern and
      eastern Savanna and Grassland vegetation in South Africa. The objective of the
      study was to record the distribution of R. microplus, and the related endemic
      Rhipicephalus decoloratus, in the central-western region of South Africa that
      comprises Albany Thicket, Fynbos and Savanna vegetation. In this survey, ticks
      were collected from 415 cattle in four provinces (Eastern Cape, Northern Cape and
      Western Cape and Free State provinces) and from the vegetation in the Eastern
      Cape province of South Africa between October 2013 and September 2015. More than
      8000 ticks were collected from cattle at 80 localities of which R. microplus was
      present at 64 localities and R. decoloratus at 47 localities. A total of 7969
      tick larvae were recorded from the vegetation at 20 localities of which 6593 were
      R. microplus and 1131 were R. decoloratus. Rhipicephalus microplus was recorded
      in each of the regions that were sampled. Rhipicephalus microplus is now present
      throughout the coastal region of the Eastern Cape province and at multiple
      localities in the north-eastern region of the Northern Cape province. It was also
      recorded in the western region of the Western Cape province and one record was
      made for the Free State province. The observed range changes may be facilitated
      by the combined effects of environmental adaptability by the tick and the
      movement of host animals.

PMID- 29227141
TI  - Cervical porcupine quill foreign body involving the spinal cord of a dog: A
      description of various imaging modality findings.
AB  - Although porcupine quill injuries are common in dogs, the detailed appearance of
      the quill on diagnostic ultrasound, computed tomography, and magnetic resonance
      imaging has not been sufficiently described. A 4-year-old, intact, female Jack
      Russel terrier presented with severe neck pain and ataxia after an altercation
      with a porcupine 2 weeks earlier. Radiology, diagnostic ultrasound, computed
      tomography and magnetic resonance imaging were all utilised to identify a quill
      imbedded in the cervical vertebral canal and cervical musculature and were
      compared to each other. Surgical removal of the quill, guided by imaging
      findings, led to the resolution of the clinical signs in the patient. Previous
      ultrasound imaging reports have just stated that the quill consists of paralell
      hyperechoic lines, and do not mention the finer hyperechoic lines inbetween and
      do not try to provide a reason for the appearance. Previous computed tomography
      (CT) reports just mention identifying the quill on CT images (whether or not CT
      could identify the fragments), but do not go into detail about the attenuating
      appearance of the quill nor try to relate this to the composition of the quill.
      This is to the authors' knowledge the first report with detailed imaging
      descriptions of a case of cranial cervical vertebral canal porcupine quill
      foreign body in a dog. This is also the first report to allude to a possible
      difference in imaging findings related to quill structure because of keratin
      orientation and melanin content. The ideal imaging modality to use remains
      elusive, but ultrasound, computed tomography and magnetic resonance imaging could
      all identify the quill.

PMID- 29227142
TI  - Perineal urethrostomy to treat obstructive urolithiasis in a captive hand-raised
      steenbok (<i>Raphicerus campestris</i>).
AB  - The steenbok (Raphicerus campestris) is a small antelope of the family Bovidae
      native to the African continent. Urolithiasis, the formation of urinary calculi
      in the urinary tract, can be caused by a variety of factors such as diet,
      dehydration, infection and anatomical predisposition. Urolithiasis, with uroliths
      identified as magnesium calcium phosphate carbonate in composition, was diagnosed
      in a hand-reared 5-month-old steenbok. Perineal urethrostomy was performed as a
      component of the broad treatment regime that included fluid therapy, antibiotic
      and anti-inflammatory treatment. However, the animal died 4 days later as a
      result of systemic hypoxia and energy depletion because of stress and cachexia.
      The challenges of post-surgical treatment, the importance of positive energy
      balance in small ruminants under stressful circumstances, as well as the role of
      diet of hand-reared antelope in predisposition to urolith formation are
      highlighted.

PMID- 29227143
TI  - Corrigendum: Ileal hypertrophy and associated true diverticulum as a cause of
      colic in a horse.
AB  - No abstract available.

PMID- 29227144
TI  - Stenosis of gastric sleeve after laparoscopic sleeve gastrectomy: clinical,
      radiographic and endoscopic findings.
AB  - OBJECTIVE: To determine the clinical, radiographic, and endoscopic findings of
      sleeve stenosis after sleeve gastrectomy and to correlate treatment with
      outcomes. METHODS: We identified 43 patients who underwent barium studies to
      evaluate upper GI symptoms after laparoscopic sleeve gastrectomy. The clinical,
      radiographic, and endoscopic findings were reviewed and correlated with treatment
      and outcomes. RESULTS: 26 patients (60%) had sleeve stenoses. All stenoses
      appeared as short segments of smooth, tapered narrowing, with a mean length of
      8.0 mm and mean width of 7.5 mm, and 24 (92%) were located in the proximal or
      distal third of the sleeve. 23 patients (88%) had upstream dilation, and 1 (4%)
      had retained food proximal to the stenosis. 23 (70%) of 33 patients with
      obstructive symptoms and 3 (30%) of 10 without obstructive symptoms had sleeve
      stenoses. Endoscopy revealed sleeve stenosis in 8 (67%) of 12 patients with
      radiographic stenosis. Endoscopic dilation resulted in improvement/resolution of
      symptoms in seven (88%) of 8 patients. CONCLUSION: Sleeve stenosis after sleeve
      gastrectomy was characterized radiographically by a short segment of smooth,
      tapered narrowing, typically in the proximal or distal third of the sleeve.
      Approximately, 70% of patients with obstructive symptoms and 30% with non
      obstructive symptoms had sleeve stenosis. One-third of radiographically diagnosed
      stenoses were not seen at endoscopy. The barium study, therefore, is a useful
      test for sleeve stenosis in patients with obstructive or nonobstructive symptoms
      after sleeve gastrectomy. Advances in knowledge: This article describes the
      appearance and location of sleeve stenoses after laparoscopic sleeve gastrectomy
      and the clinical presentation and treatment options for these patients.

PMID- 29227145
TI  - Transport-Induced Spatial Patterns of Sulfur Isotopes (delta34S) as
      Biosignatures.
AB  - Cave minerals deposited in the presence of microbes may host geochemical
      biosignatures that can be utilized to detect subsurface life on Earth, Mars, or
      other habitable worlds. The sulfur isotopic composition of gypsum (CaSO4.2H2O)
      formed in the presence of sulfur-oxidizing microbes in the Frasassi cave system,
      Italy, was evaluated as a biosignature. Sulfur isotopic compositions (delta34SV
      CDT) of gypsum sampled from cave rooms with sulfidic air varied from -11 to 
      240/00, with minor deposits of elemental sulfur having delta34S values between 
      17 and -190/00. Over centimeter-length scales, the delta34S values of gypsum
      varied by up to 8.50/00. Complementary laboratory experiments showed negligible
      fractionation during the oxidation of elemental sulfur to sulfate by
      Acidithiobacillus thiooxidans isolated from the caves. Additionally, gypsum
      precipitated in the presence and absence of microbes at acidic pH characteristic
      of the sulfidic cave walls has delta34S values that are on average 10/00 higher
      than sulfate. We therefore interpret the 8.50/00 variation in cave gypsum
      delta34S (toward more negative values) to reflect the isotopic effect of
      microbial sulfide oxidation directly to sulfate or via elemental sulfur
      intermediate. This range is similar to that expected by abiotic sulfide oxidation
      with oxygen, thus complicating the use of sulfur isotopes as a biosignature at
      centimeter-length scales. However, at the cave room (meter-length) scale,
      reactive transport modeling suggests that the overall ~130/00 variability in
      gypsum delta34S reflects isotopic distillation of circulating H2S gas due to
      microbial sulfide oxidation occurring along the cave wall-atmosphere interface.
      Systematic variations of gypsum delta34S along gas flow paths can thus be
      interpreted as biogenic given that slow, abiotic oxidation cannot produce the
      same spatial patterns over similar length scales. The expression and preservation
      potential of this biosignature is dependent on gas flow parameters and diagenetic
      processes that modify gypsum delta34S values over geological timescales. Key
      Words: Gypsum-Sulfur isotopes-Biosignature-Sulfide oxidation-Cave. Astrobiology
      18, 59-72.

PMID- 29227146
TI  - Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function
      After High-Dose Steroid Therapy: Case Report and Laboratory Study.
AB  - BACKGROUND: The use of mesenchymal stem cells from various tissue sources to
      repair injured tissues has been explored over the past decade in large
      preclinical models and is now moving into the clinic. PURPOSE: To report the case
      of a patient who exhibited compromised mesenchymal stem cell (MSC) function
      shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7
      weeks after therapy. STUDY DESIGN: Case report and controlled laboratory study.
      METHODS: A patient enrolled in a first-in-human clinical trial for autologous
      implantation of a scaffold-free tissue engineered construct (TEC) derived from
      synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy
      for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3
      week recovery period and again at 7 weeks after therapy. RESULTS: The MSC
      proliferation rates and cell surface marker expression profiles from the 3-week
      sample met conditions for further processing. However, the cells failed to
      generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid
      therapy were functional in this regard. Further in vitro studies with MSCs and
      steroids indicated that the effect of in vivo steroids was likely a direct effect
      of the drug on the MSCs. CONCLUSION: This case suggests that MSCs are transiently
      compromised after high-dose steroid therapy and that careful consideration
      regarding timing of MSC harvest is critical. CLINICAL RELEVANCE: The drug
      profiles of MSC donors and recipients must be carefully monitored to optimize
      opportunities to successfully repair damaged tissues.

PMID- 29227147
TI  - [The investigation of attitudes toward health behaviour among high school and
      university students].
AB  - INTRODUCTION: Health awareness plays an important role in our life, which
      contains attitudes as well behavioural components. Social factors influencing
      health awareness were the basis of many previous investigations, measuring the
      effect of demographical and psychological factors. However, investigation of
      these factors usually happened with separated questions. AIM: The aim of the
      present study is to test a new questionnaire, which measures health behaviour and
      attitudes related to health awareness. METHOD: In present study, the attention
      was drawn to the introduction of a new questionnaire related to health behaviour,
      attitudes toward health awareness and factors influencing those and measured on
      population in Debrecen (SHTE 2017; n = 256). RESULTS: the new measurement proved
      to be reliable based on Cronbach alpha analysis. This was created on the basis of
      focus content analysis of group conversations with 10 subscales and 35 items.
      CONCLUSIONS: It can be stated that gender, father's educational level, objective
      and subjective financial status has a significantly negative effect; while sport,
      subjective health and fitness as well as subjective religiosity have a
      significantly positive effect which reflects previous findings and confirm the
      reliability of our questionnaire. Orv Hetil. 2017; 158(44): 1754-1760.

PMID- 29227149
TI  - [Miscellaneous].

PMID- 29227150
TI  - Early Results of a Pragmatic Trial: Report to a State Agency on Acupuncture for
      the Underserved Amid the Opioid Crisis.

PMID- 29227148
TI  - Structural abnormalities and altered regional brain activity in multiple
      sclerosis with simple spinal cord involvement.
AB  - OBJECTIVE: To assess the changes of the structural and functional abnormalities
      in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using
      resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and
      diffusion tensor tractography. METHODS: The amplitude of low-frequency
      fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs)
      matched for age, gender and education were compared by using RS-fMRI. We also
      compared the volume, fractional anisotropy (FA) and apparent diffusion
      coefficient of the brain regions in baseline brain activity by using VBM and
      diffusion tensor imaging. The relationships between the expanded disability
      states scale (EDSS) scores, changed parameters of structure and function were
      further explored. RESULTS: (1) Compared with HCs, the ALFF of the bilateral
      hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly.
      However, patients exhibited increased ALFF in the left middle frontal gyrus, left
      posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test,
      after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle
      frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right
      hippocampus, the FA of left hippocampus and right middle temporal gyrus were
      significantly different. (2) A significant correlation between EDSS scores and
      ALFF was noted only in the left posterior cingulate gyrus. CONCLUSION: Our
      results detected structural and functional abnormalities in MS-SSCI and
      functional parameters were associated with clinical abnormalities. Multimodal
      imaging plays an important role in detecting structural and functional
      abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply
      RS-fMRI, VBM and diffusion tensor tractography to study the structural and
      functional abnormalities in MS-SSCI, and to explore its correlation with EDSS
      score.

PMID- 29227151
TI  - Evaluating which plan quality metrics are appropriate for use in lung SBRT.
AB  - OBJECTIVE: Several dose metrics in the categories-homogeneity, coverage,
      conformity and gradient have been proposed in literature for evaluating treatment
      plan quality. In this study, we applied these metrics to characterize and
      identify the plan quality metrics that would merit plan quality assessment in
      lung stereotactic body radiation therapy (SBRT) dose distributions. METHODS:
      Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our
      institution were retrospectively reviewed. Dose calculations were performed using
      anisotropic analytical algorithm (AAA) with heterogeneity correction. A
      literature review on published plan quality metrics in the categories-coverage,
      homogeneity, conformity and gradient was performed. For each patient, using dose
      volume histogram data, plan quality metric values were quantified and analysed.
      RESULTS: For the study, the radiation therapy oncology group (RTOG) defined plan
      quality metrics were: coverage (0.90 +/- 0.08); homogeneity (1.27 +/- 0.07);
      conformity (1.03 +/- 0.07) and gradient (4.40 +/- 0.80). Geometric conformity
      strongly correlated with conformity index (p < 0.0001). Gradient measures
      strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol
      advocated conformity guidelines for prescribed dose in all categories were met in
      >=94% of cases. The proportion of total lung volume receiving doses of 20 Gy and
      5 Gy (V20 and V5) were mean 4.8% (+/-3.2) and 16.4% (+/-9.2), respectively.
      CONCLUSION: Based on our study analyses, we recommend the following metrics as
      appropriate surrogates for establishing SBRT lung plan quality guidelines
      coverage % (ICRU 62), conformity (CN or CIPaddick) and gradient (R50%).
      Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN
      or CIPadddick in place of prescription isodose to target volume ratio for
      conformity index evaluation. Advances in knowledge: Our study metrics are
      valuable tools for establishing lung SBRT plan quality guidelines.

PMID- 29227153
TI  - Profiles by suicide methods: an analysis of older adults.
AB  - OBJECTIVE: The aim of this study was to investigate choice of suicide method in
      individuals aged 65 years and over. METHODS: Data were obtained from the
      Queensland Suicide Register, Australia. Univariate and multi-variate logistic
      regression analyses were conducted. RESULTS: The predominant methods in older
      adults were hanging (21.5%), firearms and explosives (20.9%), drug poisoning
      (18.5%), followed by other poisoning (mainly MVCO) (12.6%), suffocation by
      plastic bag (8.5%), and drowning (6%). Some methods (e.g. firearms and
      explosives, drug poisoning, suffocation) appeared characterised by profiles
      (e.g., socio-demographic and clinical aspects), meanwhile others were not well
      distinguishable. Compared to other methods, those who died by firearms and
      explosives were significantly more likely to be males, Australian born, live in
      rural and remote areas, and less likely to have a mental illness, previous
      suicide attempt(s) or leave a suicide note. Those who died by drug poisoning were
      more likely to be females, leave a suicide note, experience interpersonal
      conflict and live in urban areas. Similarly, those who chose suffocation by
      plastic bag were more likely to be older females, leave a suicide note, and pay
      attention to suicide in the media, but less likely to experience interpersonal
      conflict. CONCLUSION: Acceptability, availability and lethality are important
      factors impacting choice of means and should be considered when designing suicide
      prevention activities in older adults.

PMID- 29227152
TI  - Analysis of intra and extramyocellular lipids in the multifidus muscle in
      patients with chronic low back pain using MR spectroscopy.
AB  - OBJECTIVE: To analyse the intra- (IMCL) and extramyocellular lipids (EMCL)
      concentration in the multifidus muscle (Mm) using MR spectroscopy (MRS) in
      patients with low back pain (LBP), and to evaluate the correlation between those
      lipid concentrations and age, obesity, atrophy of the Mm and LBP intensity.
      METHODS: 60 LBP patients underwent routine diagnostic MRI of the lumbar spine
      before undergoing imaging for the study. Body mass index, as an indicator of
      obesity and visual analogue scale, as an indicator of LBP were also measured.
      Proton MRS was acquired with a single-voxel point-resolved spectroscopy sequence.
      Furthermore, the MRS volume of interest for measuring the IMCL and EMCL
      concentration at L4/5 for the right Mm was determined, and we measured the cross
      sectional area of Mm as an indicator of muscle atrophy. RESULTS: Age showed
      correlation with EMCL concentration (r = 0.314, p = 0.008). The body mass index
      showed correlation with EMCL concentration (r = 0.358, p = 0.005). The cross
      sectional area of Mm showed correlation with EMCL concentration (r = -0.543, p <
      0.001). Moreover, the LBP visual analogue scale showed correlation with IMCL
      concentration (r = 0.367, p = 0.004). CONCLUSION: There were correlations between
      age, obesity, muscle atrophy, and EMCL concentration in Mm. IMCL concentration in
      Mm showed a correlation with LBP intensity. This may suggest that IMCL
      concentration could become an effective objective indicator of chronic LBP
      intensity. Advances in knowledge: We investigated the characteristics of fat
      content in Mm with LBP patients. This study was demonstrated the association of
      the IMCL and EMCL concentration in Mm with various patient parameters.

PMID- 29227154
TI  - Pose determination of a blade implant in three dimensions from a single two
      dimensional radiograph.
AB  - The aim of the study was to introduce a mathematical method to estimate the
      correct pose of a blade by evaluating the radiographic features obtained from a
      single two-dimensional image. Blade-form implant bed preparation was performed
      using the piezosurgery device, and placement was attained with the use of
      magnetic mallet. The pose determination of the blade was described by means of
      three consecutive rotations defined by three angles of orientation (triplet phi,
      theta and psi). Retrospective analysis on periapical radiographs was performed.
      This method was used to compare implant (axial length along the marker, i.e. the
      implant structure) vs angular correction factor (a trigonometric function of the
      triplet). The accuracy of the method was tested by generating two-dimensional
      radiographic simulations of the blades, which were then compared with the images
      of the implants as appearing on the real radiographs. Two patients had to be
      excluded from further evaluation because the values of the estimated pose angles
      showed a too-wide range to be effective for a good standardization of serial
      radiographs: intrapatient range from baseline to 1-year survey was > of a
      threshold determined by the clinicians (30 degrees ). The linear dependence
      between implant (CF degrees ) and angular correction factor (CF^) was estimated
      by a robust linear regression, yielding the following coefficients: slope, 0.908;
      intercept, -0.092; and coefficient of determination, 0.924. The absolute error in
      accuracy was -0.29 +/- 4.35, 0.23 +/- 3.81 and 0.64 +/- 1.18 degrees ,
      respectively, for the angles phi, theta and psi. The present theoretical and
      experimental study established the possibility of determining, a posteriori, a
      unique triplet of angles (phi, theta and psi) which described the pose of a blade
      upon a single two-dimensional radiograph, and of suggesting a method to detect
      cases in which the standardized geometric projection failed. The angular
      correction of the bone level yielded results very close to those obtained with an
      internal marker related to the implant length.

PMID- 29227156
TI  - The Characterization of Biosignatures in Caves Using an Instrument Suite.
AB  - The search for life and habitable environments on other Solar System bodies is a
      major motivator for planetary exploration. Due to the difficulty and significance
      of detecting extant or extinct extraterrestrial life in situ, several independent
      measurements from multiple instrument techniques will bolster the community's
      confidence in making any such claim. We demonstrate the detection of subsurface
      biosignatures using a suite of instrument techniques including IR reflectance
      spectroscopy, laser-induced breakdown spectroscopy, and scanning electron
      microscopy/energy dispersive X-ray spectroscopy. We focus our measurements on
      subterranean calcium carbonate field samples, whose biosignatures are analogous
      to those that might be expected on some high-interest astrobiology targets. In
      this work, we discuss the feasibility and advantages of using each of the
      aforementioned instrument techniques for the in situ search for biosignatures and
      present results on the autonomous characterization of biosignatures using
      multivariate statistical analysis techniques. Key Words: Biosignature suites
      Caves-Mars-Life detection. Astrobiology 17, 1203-1218.

PMID- 29227155
TI  - Using Mobile Health to Improve Social Support for Low-Income Latino Patients with
      Diabetes: A Mixed-Methods Analysis of the Feasibility Trial of TExT-MED + FANS.
AB  - BACKGROUND: Social support interventions can improve diabetes self-care,
      particularly for Latinos, but are time and resource intensive. Mobile health may
      overcome these barriers by engaging and training supporters remotely. METHODS: We
      conducted a randomized controlled feasibility trial of emergency department
      patients with diabetes to determine the feasibility of enrolling patients and
      supporters, acceptability of the intervention, and preliminary efficacy results
      to power a larger trial. All patients received an existing mHealth curriculum
      (TExT-MED). After identifying a supporter, patients were randomized to
      intervention: supporters receiving FANS (family and friends network support), a
      text message support curriculum synchronized to patient messages, or control:
      supporters receiving a mailed pamphlet of the same information. Participants
      followed up at 3 months. FANS intervention participants came to postintervention
      interviews as part of a qualitative analysis. RESULTS: We enrolled 44 patients
      (22 per arm) and followed up 36 at 3 months. Participants were positive about the
      program. FANS intervention improved HbA1c (intervention mean decreased from 10.4%
      to 9.0% vs. from 10.1% to 9.5%, delta -0.8%, confidence interval [CI] -0.4 to 2,
      P = 0.30), self-monitoring of glucose (intervention increased 1.6 days/week vs.
      control decreased 2 days/week, delta 2.3 days/week, CI 4-0.6, P = 0.02), and
      physical activity (mean Godin leisure time activity score improved 16.1 vs.
      decreased 9.6 for control, delta 25.7, CI 49.2-2.3, P = 0.10). In qualitative
      analysis, patients reported improved motivation, behaviors, and relationships.
      Supporters reported making healthier decisions for themselves. CONCLUSIONS:
      mHealth is a feasible, acceptable, and promising avenue to improve social support
      and diabetes outcomes.

PMID- 29227157
TI  - Systematic review of the diagnostic accuracy of the non-English versions of
      Addenbrooke's cognitive examination - revised and III.
AB  - OBJECTIVE: This systematic review aims to review the evidence for the diagnostic
      accuracy of the non-English updated versions of Addenbrooke's Cognitive
      Examination (ACE) - the ACE-Revised (ACE-R) and the ACE-III - in the diagnosis of
      dementia. METHODS: A systematic search resulted in 16 eligible studies evaluating
      the diagnostic accuracy of ACE-R and ACE-III in ten different languages. Most
      studies were assessed as of medium to low quality using Standards for Reporting
      of Diagnostic Accuracy (STARD) guidance. RESULTS: The findings of excellent
      diagnostic accuracy are compromised by the methodological limitations of studies.
      While studies generally reported excellent diagnostic accuracy across and within
      different languages, optimal cut-offs even within particular language versions,
      varied. CONCLUSION: There is a need for future research to address these
      limitations through adherence to STARD guidelines. The ACE-III is particularly
      under-evaluated and should be a focus of future research. The variance in
      obtained optimal cut-offs within language versions is an issue compromising
      clinical utility and could be addressed in future work through use of a-priori
      defined thresholds.

PMID- 29227159
TI  - Moving on from adversity: an understanding of resilience in rural Thai older
      people.
AB  - OBJECTIVE: This study explored the concept of resilience in rural Thai older
      people. METHOD: The study was exploratory and descriptive in design. Ethnographic
      fieldwork was undertaken in four rural Thai communities. Non-participant
      observation (340 h) and 35 semi-structured interviews with older people enabled
      the collection of qualitative data. Nvivo 10 was used to collate and organise the
      qualitative data. Data analysis was conducted thematically. RESULTS: One major
      core theme and five qualitative sub-themes emerged from the data related to the
      theoretical construct of rural Thai elders' resilience. The subthemes of the core
      theme 'moving on' include: (1) keep doing a job and earning a living; (2) having
      Jai-Yai to fight for life; (3) accepting a situation (Plong and Taam-Jai); (4)
      expressing difficulty; and (5) connecting with people, beliefs and customs.
      CONCLUSION: The concept of 'moving on' provides a subcultural viewpoint of older
      rural Thai people in the face of adversity in their everyday lives. Previous
      conceptions of resilience and older people focus on it being bouncing back from
      adversity. Bouncing back implies a setback, whereas 'moving on' found in this
      study is the process of continuous movement forward and getting on with one's
      life despite difficulties.

PMID- 29227160
TI  - Inter- and intraexaminer reliability of bitewing radiography and near-infrared
      light transillumination for proximal caries detection and assessment.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the inter- and
      intraexaminer reliability of digital bitewing (DBW) radiography and near-infrared
      light transillumination (NIRT) for proximal caries detection and assessment in
      posterior teeth. METHODS: From a pool of 85 patients, 100 corresponding pairs of
      DBW and NIRT images (~1/3 healthy, ~1/3 with enamel caries and ~1/3 with dentin
      caries) were chosen. 12 dentists with different professional status and clinical
      experience repeated the evaluation in two blinded cycles. Two experienced
      dentists provided a reference diagnosis after analysing all images independently.
      Statistical analysis included the calculation of simple (kappa) and weighted
      Kappa (wkappa) values as a measure of reliability. Logistic regression with a
      backward elimination model was used to investigate the influence of the
      diagnostic method, evaluation cycle, type of tooth, and clinical experience on
      reliability. RESULTS: Altogether, inter- and intraexaminer reliability exhibited
      good to excellent kappa and wkappa values for DBW radiography (Inter: kappa =
      0.60/ 0.63; wkappa = 0.74/0.76; Intra: kappa = 0.64; wkappa = 0.77) and NIRT
      (Inter: kappa = 0.74/0.64; wkappa = 0.86/0.82; Intra: kappa = 0.68; wkappa =
      0.84). The backward elimination model revealed NIRT to be significantly more
      reliable than DBW radiography. CONCLUSIONS: This study revealed a good to
      excellent inter- and intraexaminer reliability for proximal caries detection
      using DBW and NIRT images. The logistic regression analysis revealed
      significantly better reliability for NIRT. Additionally, the first evaluation
      cycle was more reliable according to the reference diagnoses.

PMID- 29227161
TI  - Tetracycline and rifampicin induced a viable but nonculturable state in
      Staphylococcus epidermidis biofilms.
AB  - AIM: The goal of this study was to determine the effectiveness of antibiotics on
      Staphylococcus epidermidis biofilms with different proportions of dormant
      bacteria, using clinical and commensal isolates. MATERIALS & METHODS: The ability
      of S. epidermidis isolates to develop a dormant state was determined. The
      susceptibility of biofilms with prevented or induced dormancy to antibiotics was
      evaluated by enumeration of viable and cultivable cells, and confocal microscopy.
      RESULTS: Dormancy was observed in the majority of tested strains. Tetracycline
      and rifampicin enhanced the development of a viable but noncultivable biofilm
      state. CONCLUSION: Biofilms with induced dormancy were more likely to survive
      rifampicin. Furthermore, we found that the reduction of cultivable cells was not
      sufficient to reach definite conclusions on antimicrobial effectiveness.

PMID- 29227162
TI  - Electromyography Biofeedback Exergames to Enhance Grip Strength and Motivation.
AB  - BACKGROUND: Hand strength weakness affects the performance of most activities of
      daily living. This study aims to design, develop, and test an electromyography
      (EMG) biofeedback training system based on serious games to promote motivation
      and synchronization and proper work intensity in grip exercises for improving
      hand strength. MATERIALS AND METHODS: An EMG surface sensor, soft balls with
      different stiffness and three exergames, conforms the system to drive videogame
      clues in response to EMG-inferred grip strength, while overseeing motivation. An
      experiment was designed to study the effect of performing handgrip (HG) exercises
      with the proposed system versus traditional exercises. Participants, organized
      into two groups, followed a training program for each hand. One group followed a
      HG exergame training (ET) with the dominant hand and traditional HG training with
      the nondominant hand and inverse sequence by the second group. Initial and final
      grip forces were measured using a digital dynamometer. Questionnaires evaluated
      motivation and user experience, and exercise performance was evaluated in terms
      of work and rest time percentage and maximal voluntary contraction percentage
      over contraction periods. Data were analyzed for statistically significant
      differences and increase of means. RESULTS: Participants showed significantly
      better exercise performance and higher grip forces, with sustained intrinsic
      motivation and user experience, with the ET. CONCLUSION: Improvement in force
      level arises evidently from the synchronized work-rest time pattern and
      appropriated intensity of the muscle activity. This leads to support that EMG
      biofeedback exergames improve motor neurons firing and resting.

PMID- 29227165
TI  - Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A
      systematic review and meta-analysis.
AB  - Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates
      bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent
      years because of its inverse association with polycystic ovary syndrome (PCOS),
      obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta
      analysis was performed to examine the associations of SHBG with PCOS and to
      correlate serum SHBG levels with various PCOS associated endocrine and metabolic
      dysregulation as well as to determine the effects of various therapeutic agents
      on serum SHBG levels in PCOS patients in order to assess the true accuracy of
      SHBG in the prediction of PCOS. A literature search was performed using Pub-Med,
      Science direct, google scholar, EMBASE, and Cochrane library. A total of 675
      relevant records were identified, of which 62 articles were included. Meta
      analysis using a random-effects model was performed using STATA version 13 to
      calculate standardized mean difference (SMD) with 95% confidence intervals (95 %
      CIs). SHBG levels in controls were significantly higher than that of PCOS
      patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity
      across studies (I2= 93.9% and p=0.000). Our results suggest that the lower serum
      SHBG levels are associated with the risk of PCOS. SHBG may also play an important
      role in various metabolic disturbances in PCOS patients. Therapeutic
      interventions improved SHBG levels in PCOS women which further reduced PCOS
      associated complications. Therefore, SHBG levels may prove to be a useful
      biomarker for the diagnosis and treatment of PCOS. Systematic review
      registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary
      syndrome; SHBG: sex hormone-binding globulin.

PMID- 29227167
TI  - Diagnosis of platelet function disorders: A standardized, rational, and modular
      flow cytometric approach.
AB  - A high proportion of patients with mucocutaneous bleeding diathesis and suspected
      inherited or acquired platelet disorder remain without diagnosis even after
      comprehensive laboratory testing. Since flow cytometry allows investigation of
      resting and activated platelets on the single cell level by requiring only
      minimal amounts of blood, this method has become an important assay within the
      diagnostic algorithm, especially in pediatrics. We therefore developed a
      standardized and modular flow cytometric approach that contributes to clarify
      impaired platelet function in a rational step-by-step manner. Due to simultaneous
      analysis of four fluorophores in a basic panel design, we are able to readily
      detect the most common and clinically significant platelet disorders: Glanzmann
      thrombasthenia or Glanzmann-like diseases (fibrinogen receptor GPIIb-IIIa),
      Bernard-Soulier syndrome (von Willebrand-factor receptor complex GPIb-IX-V) and
      less well characterized beta1-integrins that serve as the collagen, laminin or
      fibronectin receptor (CD29-CD49b, e and f, respectively). Platelet reactivity was
      investigated in response to the agonists adenosine diphosphate (ADP) and thrombin
      receptor activator peptide 6 (TRAP6) in suboptimal and optimal concentrations by
      quantifying surface expression of activation markers CD62P and CD63 as well as
      binding of PAC-1 antibody to the high affinity conformation of the fibrinogen
      receptor. For advanced diagnostic questions, several further modules were
      implemented: (i) calcium mobilization for evaluation of early signal
      transduction, (ii) a kinetically resolved mepacrine assay for estimation of delta
      granule content and release, and (iii) a module to determine platelet reactivity
      upon additional agonists like the thromboxane A2-analogue U46619 or collagen.
      Blood withdrawn from a healthy control cohort allowed generating preliminary
      standard values for all parameters. The modules were validated by analysis of
      patients with known or suspected platelet defects (leukocyte-adhesion deficiency
      type III, Wiskott-Aldrich syndrome, acute myeloid leukemia, sickle cell disease
      and chronic immune thrombocytopenia).

PMID- 29227168
TI  - Assessment of communication abilities in multilingual children: Language rights
      or human rights?
AB  - Communication involves a sender, a receiver and a shared code operating through
      shared rules. Breach of communication results from disruption to any of these
      basic components of a communicative chain, although assessment of communication
      abilities typically focuses on senders/receivers, on two assumptions: first, that
      their command of features and rules of the language in question (the code), such
      as sounds, words or word order, as described in linguists' theorisations,
      represents the full scope of linguistic competence; and second, that languages
      are stable, homogeneous entities, unaffected by their users' communicative needs.
      Bypassing the role of the code in successful communication assigns decisive
      rights to abstract languages rather than to real-life language users, routinely
      leading to suspected or diagnosed speech-language disorder in academic and
      clinical assessment of multilingual children's communicative skills. This
      commentary reflects on whether code-driven assessment practices comply with the
      spirit of Article 19 of the Universal Declaration of Human Rights.

PMID- 29227169
TI  - Descriptive study of the relationship between the subclinical carotid disease and
      biomarkers, carotid femoral pulse wave velocity in patients with hypertension.
AB  - BACKGROUND: Carotid intima-media thickness (cIMT) is a significant early
      prediction signal for preclinical atherosclerosis. Plasma homocysteine (Hcy)
      level is an independent risk factor for cardiovascular diseases. Pulse wave
      velocity (PWV), an index of arterial stiffness (AS), has showed its value in the
      evaluation of AS in vascular-related diseases. The data regarding the
      relationships between cIMT and other indices of vascular damage are limited and
      partly controversial. We aim to investigate the relationships between cIMT and
      other indices of vascular damage such as Hcy and carotid femoral PWV (CF-PWV).
      METHODS: In total,1188 (male/female 514/674) subjects with hypertension from
      Vascular Medicine of Peking University Shougang Hospital were enrolled into our
      study. The patients with hypertension were measured bilateral cIMT by B-mode
      ultrasound and measured plasma levels of Hcy, total cholesterol (TC), high
      density lipoprotein (HDL), low-density lipoprotein (LDL), C-reactive protein
      (CRP), glucose, and other biomarkers. Plaques were detected in 78% of the study
      patients. Plasma Hcy (p < 0.001), CRP (p <  0.001), LDL (p < 0.001), HDL (p =
      0.008), TC levels (p < 0.001), and CF-PWP (p < 0.001) were significantly greater
      in hypertensive patients with carotid plaques than patients without. The carotid
      plaque detection rate (p < 0.001) and bilvertebral artery max velocity (p < 0.05)
      were significantly different in quartiles of plasma Hcy levels. R-IMT correlated
      significantly with HCY, high sensitive CRP (hs-CRP), CF-PWV, and R-vertebral
      artery intimal diameter. Age (p < 0.001) and CF-PWV (p < 0.05) predicted the
      presence of carotid plaques independently in the logistic regression. However,
      Hcy did not independently predict the presence of carotid plaques in the logistic
      regression. CONCLUSION: Increased carotid femoral PWV and elevated plasma Hcy
      levels are associated with subclinical carotid disease in hypertensive patients.
      CF-PWV independently predicted subclinical carotid plaque in the patients with
      hypertensive. While, there is insufficient evidence for Hcy in predicting plaque
      incidence.

PMID- 29227171
TI  - Evaluation and prediction of powder flowability in pharmaceutical tableting.
AB  - The focus of this study is to establish a characterization method determining the
      powder flowability in context of tableting. At first, flowability of different
      materials is measured using the ring shear tester, and its prediction from
      particle size is established. Next, the model die-filling system is presented
      which is a modified version of previous studies. Using this system, flowability
      of different materials is measured at varying die speeds. A new curve fit to
      assess die fill ratio vs die speed is suggested improving predictability, and a
      novel flowability metric, "Die Fill Index" (DFI), is derived. The DFI is
      appropriate to describe flowability for most of the tested materials, and
      sensitivity of a material with respect to tableting speed. A correlation is
      generated predicting DFI from particle size. Additionally, it is shown that model
      die filling is the preferable method to assess flowability for tableting compared
      to ring shear tester.

PMID- 29227172
TI  - A Retinal Research Nonprofit Paves the Way for Commercializing Gene Therapies.

PMID- 29227173
TI  - Changes in platelet function with inflammation in patients undergoing vascular
      surgery.
AB  - The role of platelets in ischaemic events is well established. Aspirin represents
      the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at
      the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to
      aspirin, but recent data raise uncertainty about the validity of this approach.
      Specifically, in some patients AA-induced clotting is not suppressed, but the
      level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible.
      Furthermore, AA-induced whole blood clotting varies dynamically in individuals,
      who are aspirin responsive according to TXB2 levels. The aim of this study was to
      assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in
      patients on aspirin before, during, and after major vascular surgery, which
      represents a model of on/off vascular inflammation. Firstly, we hypothesized,
      that in association with this inflammatory episode AA-, ADP- and thrombin-induced
      clotting would change in a dynamic manner. Secondly, that AA-induced clotting
      will be modified despite complete suppression of platelet TXB2 production by
      aspirin throughout the periprocedural period, possibly via a lipoxygenase
      mediated mechanism. Fourty patients underwent major vascular surgery (open
      abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb
      ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of
      aspirin prior to and throughout the perioperative period and received 5000 units
      of unfractionated heparin intraoperatively. AA-, ADP-, and thrombin-induced
      clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12-HETE)) and
      inflammatory markers (CRP, IL-6, TNF-alpha and CD40) were measured pre-procedure
      and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and
      thrombin-induced platelet reactivity was assessed using thrombelastography. TXB2,
      12-HETE, IL-6, TNF-alpha, CD40 were determined using the sequential competitive
      binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an
      immune-turbidimetric test on human serum. There was a transient rise in
      inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3
      to 5 days p < 0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p < 0.001 as
      compared to baseline). Patients had negligible levels of TXB2 throughout,
      confirming a consistent therapeutic response to aspirin. There was a transient
      rise in thrombin-mediated clotting (MAThrombin at 48 hours p = 0.001 and 3 to 5
      days p < 0.001) and a fall in AA- and ADP-induced clotting in the early post op
      period (both MAAA and MAADP p = 0.001 at 2 hours). At 3 months, the level of AA-
      and ADP-induced clotting was significantly higher than at baseline (p = 0.008 for
      MAAA and p = 0.002 for MAADP), hence demonstrating a rebound effect. These data
      demonstrate a novel dynamic variation in platelet aggregation with acute vascular
      inflammation, including AA-induced whole blood clotting which is apparently COX-1
      independent.

PMID- 29227174
TI  - Gambogic amide, a selective TrkA agonist, does not improve outcomes from
      traumatic brain injury in mice.
AB  - OBJECTIVES: There is evidence that treatment with nerve growth factor (NGF) may
      reduce neuroinflammation and apoptosis after a traumatic brain injury (TBI). NGF
      is thought to exert its effects via binding to either TrkA or p75 neurotrophin
      receptors. This study aimed to investigate the effects of a selective TrkA
      agonist, gambogic amide (GA), on TBI pathology and outcomes in mice following
      lateral fluid percussion injury. METHODS: Male C57BL/6 mice were given either a
      TBI or sham injury, and then received subcutaneous injections of either 2 mg/kg
      of GA or vehicle at 1, 24, and 48 h post-injury. Following behavioural studies,
      mice were euthanized at 72 h post-injury for analysis of neuroinflammatory,
      apoptotic, and neurite outgrowth markers. RESULTS: Behavioural testing revealed
      that GA did not mitigate motor deficits after TBI. TBI caused an increase in
      cortical and hippocampal expression of several markers of neuroinflammation and
      apoptosis compared to sham groups. GA treatment did not attenuate these increases
      in expression, possibly contributed to by our finding of TrkA receptor down
      regulation post-TBI. CONCLUSIONS: These findings suggest that GA treatment may
      not be suitable for attenuating TBI pathology and improving outcomes.

PMID- 29227175
TI  - Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on
      colonic transit time and gastrointestinal symptoms in adults with functional
      constipation: A double-blind, randomized, placebo-controlled, and dose-ranging
      trial.
AB  - Bifidobacterium animalis subsp. lactis HN019 (HN019) ameliorates chronic
      idiopathic constipation. Our aim was to determine the efficacy and safety of 28
      day supplementation with 1 * 109 or 1 * 1010 CFU of HN019/day for constipation. A
      total of 228 adults who were diagnosed with functional constipation according to
      the Rome III criteria were randomized in a double-blind and placebo-controlled
      trial. Colonic transit time (CTT), the primary outcome, and secondary outcomes
      that were measured using inventories-patient assessment of constipation symptoms
      (PAC-SYM) and quality of life (PAC-QoL), bowel function index (BFI), bowel
      movement frequency (BMF), stool consistency, degree of straining, bowel emptying,
      bloating, and pain severity-were assessed. Ancillary parameters and harms were
      also evaluated. There were no statistically significant differences in the
      primary or secondary outcomes between interventions. A post hoc analysis of 65
      participants with fewer than 3 bowel movements per week (BMF <= 3/week) showed a
      physiologically relevant increase in weekly BMF in the high- (+2.0) and low-dose
      (+1.7) HN019 groups-by RMANOVA, the HN019 groups with BMF <= 3/week, pooled
      together, had a higher BMF versus placebo (P value = 0.01). Thus, improving low
      stool frequency could be a target of future interventions with HN019. High-dose
      HN019 also decreased the degree of straining at Day 28 versus placebo in those
      with BMF <= 3/week (P value = 0.02). Three unlikely related AEs-2 with low-dose
      HN019 and 1 with placebo-were followed until full recovery. In conclusion,
      although there were no differences in the primary analysis, HN019 is well
      tolerated and improves BMF in adults with low stool frequency.

PMID- 29227176
TI  - Metabolomics Approach in the Study of the Well-Defined Polyherbal Preparation
      Zyflamend.
AB  - Zyflamend is a highly controlled blend of 10 herbal extracts that synergistically
      impact multiple cell signaling pathways with anticancer and anti-inflammatory
      properties. More recently, its effects were shown to also modify cellular
      energetics, for example, activation of fatty acid oxidation and inhibition of
      lipogenesis. However, its general metabolic effects in vivo have yet to be
      explored. The objective of this study was to characterize the tissue specific
      metabolomes in response to supplementation of Zyflamend in mice, with a
      comparison of equivalent metabolomics data generated in plasma from humans
      supplemented with Zyflamend. Because Zyflamend has been shown to activate AMPK,
      the "energy sensor" of the cell, in vitro, the effects of Zyflamend on adiposity
      were also tested in the murine model. C57BL/6 mice were fed diets that mimicked
      the macro- and micronutrient composition of the U.S. diet with and without
      Zyflamend supplementation at human equivalent doses. Untargeted metabolomics was
      performed in liver, skeletal muscle, adipose, and plasma from mice consuming
      Zyflamend and in plasma from humans supplemented with Zyflamend at an equivalent
      dose. Adiposity in mice was significantly reduced in the Zyflamend-treated
      animals (compared with controls) without affecting body weight or weight gain.
      Based on KEGG pathway enrichment, purine and pyrimidine metabolism (potential
      regulators of AMPK) were particularly responsive to Zyflamend across all tissues,
      but only in mice. Consistent with the metabolomics data, Zyflamend activated AMPK
      and inhibited acetyl CoA-carboxylase in adipose tissue, key regulators of
      lipogenesis. Zyflamend reduces adipose tissue in mice through a mechanism that
      likely involves the activation of AMPK.

PMID- 29227177
TI  - Immunogenicity and safety of inactivated chromatographically purified Vero cell
      derived Japanese encephalitis vaccine in Thai children.
AB  - : Inactivated mouse-brain-derived Japanese encephalitis vaccine has a worrisome
      safety profile and the live attenuated vaccine is unsuitable in immunodeficiency.
      This study aimed to evaluate the immunogenicity and safety of an inactivated
      chromatographically purified Vero-cell-derived JE vaccine (CVI-JE, Beijing P-3
      strain) in children. 152 healthy Thai children, with an average (SD) age of 14.4
      (3.8) months, received 3 doses of CVI-JE on days 0, 7-28, and one year.
      Homologous JE neutralizing antibody titers (NT) were measured. All subjects had
      seroprotection [geometric mean titer (GMT) 150] 28 days' post 2nd vaccination.
      The seroprotection rates at 1 year after primary series and and 1 month after the
      booster were 89.3% (GMT 49) and 100% (GMT 621), respectively. Local and systemic
      reactions-fever (17.6%), vomiting (8%), and poor appetite (5.3%)-were noted
      within 28 days' post-vaccination. All these symptoms were self-limited.
      CONCLUSIONS: CVI-JE is safe, immunogenic, and provided high NT.

PMID- 29227178
TI  - Neuronal pathophysiology featuring PrPC and its control over Ca2+ metabolism.
AB  - Calcium (Ca2+) is an intracellular second messenger that ubiquitously masters
      remarkably diverse biological processes, including cell death. Growing evidence
      substantiates an involvement of the prion protein (PrPC) in regulating neuronal
      Ca2+ homeostasis, which could rationalize most of the wide range of functions
      ascribed to the protein. We have recently demonstrated that PrPC controls
      extracellular Ca2+ fluxes, and mitochondrial Ca2+ uptake, in neurons stimulated
      with glutamate (De Mario et al., J Cell Sci 2017; 130:2736-46), suggesting that
      PrPC protects neurons from threatening Ca2+ overloads and excitotoxicity. In
      light of these results and of recent reports in the literature, here we review
      the connection of PrPC with Ca2+ metabolism and also provide some speculative
      hints on the physiologic outcomes of this link. In addition, because PrPC is
      implicated in neurodegenerative diseases, including prion disorders and
      Alzheimer's disease, we will also discuss possible ways by which disruption of
      PrPC-Ca2+ association could be mechanistically connected with these pathologies.

PMID- 29227180
TI  - Removal of the cecum affects intestinal fermentation, enteric bacterial community
      structure, and acute colitis in mice.
AB  - The murine cecum is a major site of fermentation of dietary materials, and
      production of short chain fatty acids (SCFAs). To examine the role that the cecum
      plays in acute bacterial infection in mice, the cecum was surgically removed, and
      changes in bacterial communities and production of SCFAs were analyzed relative
      to surgical sham animals. To incite bacterial colitis, mice were orally
      challenged with Citrobacter rodentium. The impact of butyrate administered
      directly into the colon was also examined. Concentrations of SCFAs in feces were
      substantially lower in mice with an excised cecum. Bacterial communities were
      also less diverse in cecectomized mice, and densities of major SCFA-producing
      taxa including bacteria within the Ruminococcaceae and Lachnospiraceae families
      were reduced. Colonization of the intestine by C. rodentium was not affected by
      removal of the cecum, and the bacterium equally incited acute colitis in mice
      with and without a cecum. However, cecectomized mice exhibited lower body weights
      at later stages of infection indicating an impaired ability to recover following
      challenge with C. rodentium. Furthermore, removal of the cecum altered immune and
      inflammatory responses to infection including increased inflammatory markers in
      the proximal colon (Tnfalpha, Il10, betad1), and heightened inflammatory response
      in the proximal and distal colon (Ifngamma, Tnfalpha, Relmbeta). Exogenous
      administration of butyrate was insufficient to normalize responses to C.
      rodentium in cecectomized mice. The murine cecum plays a critical role in
      maintaining intestinal health, and the murine cecectomy model may be a useful
      tool in elucidating key aspects of intestine-pathogen-microbiota interactions.

PMID- 29227182
TI  - First Report of the Plasmid-Mediated Colistin Resistance Gene mcr-1 in
      Escherichia coli ST405 Isolated from Wildlife in Bejaia, Algeria.
AB  - BACKGROUND: The aim of the present study was to screen for the presence of mcr-1
      gene in Enterobacteriaceae isolated from Barbary macaques (Macaca sylvanus) in
      Algeria. MATERIALS AND METHODS: From January to April 2016, a total of 86 fresh
      stool samples from Barbary macaques were collected in the Toudja forest (Bejaia,
      Algeria). After isolation, the isolates were identified by matrix-assisted laser
      desorption and ionization time-of-flight mass spectrometry. Antibiotic
      susceptibility was determined by disk diffusion method, and minimum inhibitory
      concentration (MIC) of colistin was determined by E-test. Polymerase chain
      reaction (PCR) and sequencing were used to identify mcr-1gene. The sequence type
      (ST) was done using multilocus sequence typing. Phylogenetic groups of
      Escherichia coli and the presence of virulence genes were determined by PCR.
      Transfer of mcr-1 and extended-spectrum beta-lactamase genes was assessed by
      conjugation and transformation experiments. RESULTS: E. coli M076 isolate was
      found resistant to colistin with a MIC of 4 mg/L and to other antibiotic
      families, including beta-lactams, aminoglycosides, and fluoroquinolones. PCR and
      sequencing revealed that this isolate harbored the mcr-1, blaCTX-M-15, blaTEM-1,
      and qnrB19 genes. This isolate was assigned to ST405, belonged to phylogroup D,
      and contains only one virulence gene fyuA (siderophore uptake receptor). Neither
      transconjugants nor transformants were obtained for this isolate. CONCLUSION: In
      this study, we report the detection of mcr-1 gene producing E. coli from wild
      animals.

PMID- 29227181
TI  - Effects of fuel components and combustion particle physicochemical properties on
      toxicological responses of lung cells.
AB  - The physicochemical properties of combustion particles that promote lung toxicity
      are not fully understood, hindered by the fact that combustion particles vary
      based on the fuel and combustion conditions. Real-world combustion-particle
      properties also continually change as new fuels are implemented, engines age, and
      engine technologies evolve. This work used laboratory-generated particles
      produced under controlled combustion conditions in an effort to understand the
      relationship between different particle properties and the activation of
      established toxicological outcomes in human lung cells (H441 and THP-1).
      Particles were generated from controlled combustion of two simple biofuel/diesel
      surrogates (methyl decanoate and dodecane/biofuel-blended diesel (BD), and
      butanol and dodecane/alcohol-blended diesel (AD)) and compared to a widely
      studied reference diesel (RD) particle (NIST SRM2975/RD). BD, AD, and RD
      particles exhibited differences in size, surface area, extractable chemical mass,
      and the content of individual polycyclic aromatic hydrocarbons (PAHs). Some of
      these differences were directly associated with different effects on biological
      responses. BD particles had the greatest surface area, amount of extractable
      material, and oxidizing potential. These particles and extracts induced
      cytochrome P450 1A1 and 1B1 enzyme mRNA in lung cells. AD particles and extracts
      had the greatest total PAH content and also caused CYP1A1 and 1B1 mRNA induction.
      The RD extract contained the highest relative concentration of 2-ring PAHs and
      stimulated the greatest level of interleukin-8 (IL-8) and tumor necrosis factor
      alpha (TNFalpha) cytokine secretion. Finally, AD and RD were more potent
      activators of TRPA1 than BD, and while neither the TRPA1 antagonist HC-030031 nor
      the antioxidant N-acetylcysteine (NAC) affected CYP1A1 or 1B1 mRNA induction,
      both inhibitors reduced IL-8 secretion and mRNA induction. These results
      highlight that differences in fuel and combustion conditions affect the
      physicochemical properties of particles, and these differences, in turn, affect
      commonly studied biological/toxicological responses.

PMID- 29227183
TI  - Factors Associated with Medical Doctors' Intentions to Discriminate Against
      Transgender Patients in Kuala Lumpur, Malaysia.
AB  - PURPOSE: Transgender people are frequent targets of discrimination.
      Discrimination against transgender people in the context of healthcare can lead
      to poor health outcomes and facilitate the growth of health disparities. This
      study explores factors associated with medical doctors' intentions to
      discriminate against transgender people in Malaysia. METHODS: A total of 436
      physicians at two major university medical centers in Kuala Lumpur, Malaysia,
      completed an online survey. Sociodemographic characteristics, stigma-related
      constructs, and intentions to discriminate against transgender people were
      measured. Bivariate and multivariate linear regression were used to evaluate
      independent covariates of discrimination intent. RESULTS: Medical doctors who
      felt more fearful of transgender people and more personal shame associated with
      transgender people expressed greater intention to discriminate against
      transgender people, whereas doctors who endorsed the belief that transgender
      people deserve good care reported lower discrimination intent. Stigma-related
      constructs accounted for 42% of the variance and 8% was accounted for by
      sociodemographic characteristics. CONCLUSIONS: Constructs associated with
      transgender stigma play an important role in medical doctors' intentions to
      discriminate against transgender patients. Development of interventions to
      improve medical doctors' knowledge about and attitudes toward transgender people
      are necessary to reduce discriminatory intent in healthcare settings.

PMID- 29227184
TI  - Curing of [PSI+] by Hsp104 Overexpression: Clues to solving the puzzle.
AB  - The yeast [PSI+] prion, which is the amyloid form of Sup35, has the unusual
      property of being cured not only by the inactivation of, but also by the
      overexpression of Hsp104. Even though this latter observation was made more than
      two decades ago, the mechanism of curing by Hsp104 overexpression has remained
      controversial. This question has been investigated in depth by our laboratory by
      combining live cell imaging of GFP-labeled Sup35 with standard plating assays of
      yeast overexpressing Hsp104. We will discuss why the curing of [PSI+] by Hsp104
      overexpression is not compatible with a mechanism of either inhibition of
      severing of the prion seeds or asymmetric segregation of the seeds. Instead, our
      recent data (J. Biol. Chem. 292:8630-8641) indicate that curing is due to
      dissolution of the prion seeds, which in turn is dependent on the trimming
      activity of Hsp104. This trimming activity decreases the size of the seeds by
      dissociating monomers from the fibers, but unlike Hsp104 severing activity, it
      does not increase the number of prion seeds. Finally, we will discuss the other
      factors that affect the curing of [PSI+] by Hsp104 overexpression and how these
      factors may relate to the trimming activity of Hsp104.

PMID- 29227185
TI  - Alternative Drug Delivery for Patients Undergoing Cataract Surgery as
      Demonstrated in a Canine Model.
AB  - PURPOSE: (1) To determine ketorolac concentrations in selected ocular tissues
      following the intracameral administration of phenylephrine and ketorolac
      injection 1%/0.3% (OMIDRIA(r)) delivered in irrigation solution during lens
      replacement surgery in beagle dogs. (2) To compare the ketorolac initial dose and
      resultant concentrations from the above study to those achieved in aqueous and
      vitreous by topical administration in patients undergoing cataract surgery or
      vitrectomy, respectively. METHODS: Lens replacement surgery with
      phacoemulsification was performed in 20 female beagle dogs. A fixed combination
      of phenylephrine and ketorolac injection 1%/0.3% was diluted 125-fold into the
      balanced salt solution and delivered intracamerally during the
      phacoemulsification procedure. Ketorolac concentration was determined by liquid
      chromatography/mass spectrometry. RESULTS: Concentrations of ketorolac when
      administered by the intracameral route in the dosing solution in dogs were found
      to be considerably higher in both aqueous and vitreous compared to what is
      achieved with topical dosing in patients. CONCLUSIONS: Adequate therapeutic
      concentrations of ketorolac in aqueous and vitreous humor were achieved even at
      10 h postdose. Critical concentrations in the aqueous that envelopes the
      iris/ciliary body, which are sites of prostaglandin E2 synthesis, and the
      vitreous are not achieved by topical dosing in clinical studies after the
      surgery, but are by direct intracameral dosing as determined in this study. Based
      on these studies and clinical data, phenylephrine and ketorolac injection 1%/0.3%
      delivered during surgery as an irrigation solution may preclude the need for
      topically administered pre- and postoperative NSAIDs.

PMID- 29227186
TI  - Diversity of CTX-M Extended-Spectrum beta-Lactamases in Escherichia coli Isolates
      from Retail Raw Ground Beef: First Report of CTX-M-24 and CTX-M-32 in Algeria.
AB  - The aim of this study was to investigate the prevalence and molecular features of
      extended-spectrum cephalosporin resistance in Escherichia coli isolates
      contaminating ground beef at retail in Algeria. Of 371 ground beef samples, 27.5%
      were found to contain cefotaxime-resistant E. coli isolates distributed into A
      (24.5%), B1 (60.8%), and D (14.7%) phylogroups. A rate of 88.2% of isolates had a
      multidrug-resistance phenotype. All strains were producers of CTX-M type extended
      spectrum beta-lactamases (ESBLs): CTX-M-1, CTX-M-3, CTX-M-14, CTX-M-15, CTX-M-24,
      or CTX-M-32. Conjugation assays allowed the transfer of blaCTX-M-1 in association
      with IncI1 plasmids, blaCTX-M-15 with IncI1 and IncK+B/O plasmids, blaCTX-M-3
      with IncK plasmids, and blaCTX-M-14 with IncF1B or IncK plasmids. Sequence
      analysis of gyrA and parC genes showed mutations in 98.6% of ciprofloxacin
      resistant isolates. The patterns "GyrA: S83L+D87N, ParC: S80I" (46.5%) and "ParC:
      S80I" (42.3%) were predominant. qnrS1, qnrB, and aac(6')-Ib-cr were detected in
      18.7% of isolates. The tet genes, tetA, tetB, and tetA+tetB, were present in
      95.7% of tetracycline-resistant isolates. The sul genes (sul1, sul2, sul3,
      sul1+sul2, sul2+sul3, and sul1+sul3) and the dfr gene clusters (dfrA1, dfrA5,
      dfrA7, dfrA8, dfrA12, dfrA5+dfrA12, dfrA1+dfrA5, dfrA7+dfrA12, dfrA5+dfrA7, and
      dfrA1+dfrA5+dfrA7) were found in 96.4% and 85.5% of sulfamethoxazole/trimethoprim
      resistant isolates, respectively. Classes 1 and 2 integrons were detected in
      67.6% and 9.8% of isolates, respectively. This study highlighted the significant
      presence of resistance genes, in particular those of CTXM ESBLs, in the beef
      meat, with the risk of their transmission to humans through food chain.

PMID- 29227187
TI  - Laparoscopic Sleeve Gastrectomy: Endoscopic Findings and Gastroesophageal Reflux
      Symptoms at 18-Month Follow-Up.
AB  - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) has shown excellent results
      in terms of weight loss and resolution of comorbidities. Despite that, the effect
      of LSG on gastroesophageal reflux disease (GERD) is still a controversial topic.
      Our objective was to evaluate the presence of gastroesophageal reflux symptoms,
      erosive esophagitis (EE), and hiatal hernia (HH) in obese patients undergoing
      LSG. METHODS: Prospective observational study. LSG patients were studied before
      and at 18-month follow-up. Demographics, anthropometrics, status of
      comorbidities, perioperative data, GERD symptoms, and esophagogastroduodenoscopy
      (EGD) findings were evaluated. RESULTS: Between June 2012 and July 2014, 285
      patients underwent LSG. Pre- and postoperative data were available in 109
      patients; therefore, they were included in the study. There were 72 women (66%),
      age 40 +/- 9 years. Preoperative body mass index (BMI) was 47.8 +/- 16 kg/m2. At
      18-month follow-up, body mass index and percentage excess weight loss were 29.3
      +/- 6 kg/m2 and 64% +/- 9.4%, respectively. Resolution/improvement of
      comorbidities was as follows: diabetes 73%, hypertension 57.5%, and obstructive
      sleep apnea 89%. GERD symptoms increased from 33% to 44% (P = no statistical
      significance), EE from 20.1% (100% grade A) to 33.9% (74% grade A) (P < .001),
      and HH from 22% to 34.8% (P < .001). Postoperative findings on symptomatic
      patients were as follows: EE was found in 64.5%, HH in 23%, while 12.5% had
      normal EGD. There was a significant association between manifestation of GERD
      symptoms and the presence of EE on EGD (P < .05). Symptoms de novo were observed
      in 36.9% of patients, EE in 28.7%, and HH in 16.4%. Complication rate was 3.5%;
      there was no mortality. CONCLUSION: The prevalence of GERD symptoms, EE, and HH
      was increased after LSG. At 18-month follow-up, severity of esophagitis was mild,
      the majority of them being Grade A esophagitis. There was good correlation
      between manifestation of GERD symptoms and the presence of EE on EGD.

PMID- 29227188
TI  - Clinical Strains of Chryseobacterium and Elizabethkingia spp. Isolated from
      Pediatric Patients in a University Hospital: Performance of MALDI-TOF MS-Based
      Identification, Antimicrobial Susceptibilities, and Baseline Patient
      Characteristics.
AB  - Our objective was to evaluate the performance of matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of
      the Chryseobacterium and Elizabethkingia spp. isolated from pediatric patients at
      Hacettepe University Hospital using 16S rRNA gene sequencing as the gold standard
      and to determine the antimicrobial susceptibility patterns of the isolates and
      baseline characteristics of patients. All stored Chryseobacterium and
      Elizabethkingia spp. isolated from various clinical specimens (sputum, blood, and
      urine) of pediatric patients at Hacettepe University Hospital between 2012 and
      2016 were included in this study. Minimum inhibitory concentrations of 10
      antimicrobial agents were determined by Etest for all isolates. To determine the
      baseline characteristics of patients, medical records of all patients were
      retrospectively reviewed. In total, 18 isolates of Chryseobacterium spp. (16 C.
      indologenes, 2 C. gleum) and 5 isolates of Elizabethkingia spp. (3 E.
      meningoseptica, 2 E. anophelis) were identified by 16S rRNA sequencing. MALDI-TOF
      MS correctly identified 19 (82.6%) isolates to the species level. The quinolones
      (ciprofloxacin and levofloxacin), trimethoprim/sulfamethoxazole and
      piperacillin/tazobactam showed the highest spectrum of activity against the
      overall collection of isolates. Cystic fibrosis (CF) was the underlying disease
      in 81.8% of patients. To our knowledge, this study includes the largest number of
      Chryseobacterium spp. isolated from clinical specimens of pediatric patients in
      Turkey. In this study, we also report the first clinical isolate of E. anophelis
      in Turkey. Since, the majority of strains were isolated from patients with CF;
      larger, prospective clinical studies are needed to establish whether
      chryseobacteria could be considered as an emerging opportunistic pathogen in
      patients with CF.

PMID- 29227189
TI  - Plant molecular responses to the elevated ambient temperatures expected under
      global climate change.
AB  - Environmental temperatures affect plant distribution, growth, and development.
      The Intergovernmental Panel on Climate Change (IPCC) predicts that global
      temperatures will rise by at least 1.5 degrees C by the end of this century.
      Global temperature changes have already had a discernable impact on agriculture,
      phenology, and ecosystems. At the molecular level, extensive literature exists on
      the mechanism controlling plant responses to high temperature stress. However,
      few studies have focused on the molecular mechanisms behind plant responses to
      mild increases in ambient temperature. Previous research has found that
      moderately higher ambient temperatures can induce hypocotyl elongation and early
      flowering. Recent evidence demonstrates roles for the phytohormones auxin and
      ethylene in adaptive growth of plant roots to slightly higher ambient
      temperatures.

PMID- 29227190
TI  - Determination of propineb and its metabolites propylenethiourea and
      propylenediamine in banana and soil using gas chromatography with flame
      photometric detection and LC-MS/MS analysis.
AB  - A sensitive and specific method for the determination of propineb and its
      metabolites, propylenethiourea (PTU) and propylenediamine (PDA), using gas
      chromatography with flame photometric detection (GC-FPD) and LC-MS/MS was
      developed and validated. Propineb and its metabolite residue dynamics in
      supervised field trials under Good Agricultural Practice (GAP) conditions in
      banana and soil were studied. Recovery of propineb (as CS2), PDA and PTU ranged
      from 75.3 to 115.4% with RSD (n = 5) of 1.3-11.1%. The limit of quantification
      (LOQ) of CS2, PDA and PTU ranged from 0.005 to 0.01 mg kg-1, and the limit of
      detection (LOD) ranged from 0.0015 to 0.0033 mg kg-1. Dissipation experiments
      showed that the half-life of propineb in banana and soil ranged from 4.4 to 13.3
      days. PTU was found in banana with a half-life of 31.5-69.3 days, while levels of
      PDA were less than 0.01 mg kg-1 in banana and soil. It has been suggested that
      PTU is the major metabolite of propineb in banana. The method was demonstrated to
      be reliable and sensitive for the routine monitoring of propineb and its
      metabolites in banana and soil. It also serves as a reference for the detection
      and monitoring of dithiocarbamates (DTCs) residues and the evaluation of their
      metabolic pathway.

PMID- 29227191
TI  - Racemic, R-, and S-tebuconazole altered chitinase and chitobiase activity of
      Daphnia magna.
AB  - Tebuconazole is a chiral trizole fungicide and widely used in many crops for
      controlling disease. Tebuconazole is potential toxic to some aquatic organisms
      but relative information of its isomers is scarce. To detect the endocrine
      disrupting effects and difference of rac-, R-, and S-tebuconazole, the chitinase
      activity in Daphnia magna and chitobiase activity in each test medium were used
      as biomonitors after a 14-day exposure. Results showed that chitinase activity
      was significantly reduced by rac-, R-, and S-tebuconazole. The chitobiase
      activity in the test medium was reduced by rac- and R-tebuconazole before day 10,
      and only one peak was observed at day 10 or day 12 compared with two obvious
      peaks in the control group (days 6 and 12). S-tebuconazole delayed and reduced
      the reproduction of D. magna, but did not delay the first chitobiase activity
      peak, whereas the second peak could not be characterized as the exposure
      concentration and time increased. Compared with chitinase activity, chitobiase
      activity can still be used as a rudimentary model for identifying molt
      interfering xenobiotics, and further studies should focus on the analysis of
      correlations between these parameters.

PMID- 29227192
TI  - Coiled-coil motif in LBD16 and LBD18 transcription factors are critical for
      dimerization and biological function in arabidopsis.
AB  - The LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) gene family members encode a
      class of plant-specific transcription factors that play important roles in many
      different aspects of plant growth and development. The LBD proteins contain a
      conserved LOB domain harboring a Leu zipper-like coiled-coil motif, which has
      been predicted to mediate protein-protein interactions among the LBD family
      members. Dimerization of transcription factors is crucial for the modulation of
      their DNA-binding affinity, specificity, and diversity, contributing to the
      transcriptional regulation of distinct cellular and biological responses. Our
      various molecular and biochemical experiments with genetic approaches on LBD16
      and LBD18, which are known to control lateral root development in Arabidopsis,
      demonstrated that the conserved Leu or Val residues in the coiled-coil motifs of
      these transcription factors are critical for their dimerization as well as the
      transcriptional regulation to display their biological functions during lateral
      root formation. We further showed that beside the coiled-coil motif, the carboxyl
      terminal region in LBD18 acts as an additional dimerization domain. These
      findings provide a molecular framework for the homo- and hetero-dimerization of
      the LBD family proteins for displaying their distinct and diverse biological
      functions in plants.

PMID- 29227194
TI  - TOR signaling downregulation increases resistance to the cereal killer Fusarium
      graminearum.
AB  - TOR is the master regulator of growth and development that senses energy
      availability. Biotic stress perturbs metabolic and energy homeostasis, making TOR
      a good candidate to participate in the plant response. Fusarium graminearum
      (Fusarium) produces important losses in many crops all over the world. To date,
      the role of TOR in Fusarium infection has remained unexplored. Here, we show that
      the resistance to the pathogen increases in different Arabidopsis mutants
      impaired in TOR complex or in wild-type plants treated with a TOR inhibitor. We
      conclude that TOR signaling is involved in plant defense against Fusarium.

PMID- 29227195
TI  - A New Method for Laparoscopic Stamm Gastrostomy.
AB  - BACKGROUND/OBJECTIVE: Many methods of laparoscopic gastrostomy have been
      described, but in the majority of these, purse-string sutures and fixation of the
      stomach to the abdominal wall are not performed simultaneously. In this study, we
      aim to present a new laparoscopic gastrostomy tube (GT) placement method
      developed in accordance with the classical Stamm method. MATERIALS AND METHODS:
      Intracorporeal purse-string suture is placed at the anterior wall of the stomach
      where the GT is intended to be placed. While purse-string sutures are being
      placed, in each bite, the needle is passed through from a loop thread prepared by
      extracorporeal and the two threads are suspended outside. The stomach is
      punctured with the hook cautery, the GT is inserted, and both threads are knotted
      outside the abdomen. RESULTS: We prospectively placed GT by using our method in
      16 patients with an average age of 5 years and most of them with neurological
      developmental delay. Fundoplication was performed in most of the cases in the
      same session. No complications were encountered. CONCLUSIONS: Our method is a
      feasible approach for GT placement by the purse-string suturing and the fixation
      of the stomach to the abdominal wall without extending the port incision.

PMID- 29227193
TI  - DDX5/p68 associated lncRNA LOC284454 is differentially expressed in human cancers
      and modulates gene expression.
AB  - Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of
      gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is
      involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and
      mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells
      to identify the complete repertoire of DDX5/p68 interacting transcripts including
      73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the
      list of SE lncRNAs which we have characterized in detail for its molecular
      features and cellular functions. The RNA is located in the same primary
      transcript harboring miR-23a~27a~24-2 cluster. LOC284454 is a stable, nuclear
      restricted and chromatin associated lncRNA. The sequence is conserved only in
      primates among 26 different species and is expressed in multiple human tissues.
      Expression of LOC284454 is significantly reduced in breast, prostate, uterus and
      kidney cancer and also in breast cancer cell lines (MCF7 and T47D). Global gene
      expression studies upon loss and gain of function of LOC284454 revealed
      perturbation of genes related to cancer-related pathways. Focal adhesion and cell
      migration pathway genes are downregulated under overexpression condition, and
      these genes are significantly upregulated in breast cancer cell lines as well as
      breast cancer tissue samples suggesting a functional role of LOC284454 lncRNA in
      breast cancer pathobiology.

PMID- 29227196
TI  - Immunotherapeutics for the treatment of prostate cancer: a patent landscape based
      on key therapeutic mechanisms of actions.
AB  - The area of immunotherapeutics for the treatment of metastatic castrate-resistant
      prostate cancer has made significant progress since the autologous cell-based
      vaccine sipuleucel T became the first and to date only immunotherapy for its
      treatment. This review focuses on a broad patent landscaping exercise of this
      therapeutic area and considers if basing this landscaping on key mechanisms of
      action is appropriate to elicit the main patenting trends.

PMID- 29227197
TI  - Moderating Factors in Tissue Tonometry and Bioimpedance Spectroscopy Measures in
      the Lower Extremity of Healthy Young People in Australia and Myanmar.
AB  - BACKGROUND: Expected values for tissue tonometry and bioimpedance spectroscopy
      (BIS) in the lower extremity of young people have not been established. These
      measures are commonly used to assess tissue changes in adult, breast cancer
      related lymphedema of the arm. In tropical regions, identification of tissue
      changes in the lower limbs related to lymphatic filariasis is required; hence
      expected values and factors contributing to variation in tissue tonometry and BIS
      in two tropical populations were investigated. METHODS AND RESULTS: A convenience
      sample of healthy volunteers aged 8-21 in Myanmar and Australia was recruited.
      Tissue compressibility at the calf and anterior and posterior thigh was measured
      using three tonometry devices and free fluid in each leg was assessed using BIS.
      Data were collected about possible modifiers: leg dominance, age, gender, body
      mass index (BMI), hydration, and menstrual cycle. Paired t-test and linear
      regression compared the objective measures with possible modifiers within each
      population. Statistical significance was set at p < 0.05 with a 95% confidence
      interval. In Myanmar, increases in free fluid, tissue compressibility, and limb
      circumference were associated with being older, female, underweight, or in the
      second half of the menstrual cycle. In young Australians, increases in tissue
      compressibility and limb circumference were associated with being older or in the
      second half of the menstrual cycle. CONCLUSION: When assessing tissue
      compressibility and free fluid in young people using tonometry and gender, BIS,
      limb dominance and BMI should be considered in a local context and attempts
      should be made to minimize the potential influences of hydration and the female
      menstrual cycle.

PMID- 29227198
TI  - Novel platinum compounds and nanoparticles as anticancer agents.
AB  - Since the approval of cisplatin in 1979, platinum-based drugs have been regularly
      used in cancer chemotherapy as a first-line treatment or with the combination of
      other nonplatinum drugs. Subsequent approval of second- and third-generation
      drugs such as carboplatin and oxaliplatin respectively, has widened the
      therapeutic achievement of platinum compounds. There are few other platinum drugs
      approved recently and many other new drugs as well as the formulations of the old
      ones are going through clinical trials now. Considering the astonishing
      achievement of these drugs, analyses on the overall scenario of the patent
      applications on platinum compounds have become the priority to the scientific
      community. This review summarizes the published patent applications on the novel
      platinum anticancer compounds from 2012 to 2017 (August).

PMID- 29227199
TI  - Two-Step Irradiance Treatment Can Achieve Excellent Pain Control During Red Light
      5-Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses.
AB  - OBJECTIVE: To evaluate the ability of two-step irradiance to maintain pain
      control during red light 5-aminolevulinic acid (ALA) photodynamic therapy (PDT)
      for actinic keratoses (AK) and assess factors influencing pain. BACKGROUND: PDT
      provides excellent clinical and cosmetic results in the treatment AK and early
      basal cell carcinomas (BCC). Widespread use of PDT is limited, in part, by pain.
      A two-step irradiance method for PDT has previously been shown to significantly
      reduce PDT-associated pain during the treatment of BCC, but the ability of this
      method to limit pain during the treatment of AKs has not been reported. METHODS:
      We performed a retrospective chart review to assess the level of pain during AK
      treatment by red light PDT (n = 99). Natural density filter was used to reduce
      the irradiance of the light source and initially 10 J/cm2 dose was delivered at
      35 mW/cm2 and then, 65 J/cm2 dose was delivered at 70 mW/cm2. Pain level was
      measured using a 10-point visual analog scale at three points during the
      procedure. RESULTS: Pain was low to moderate in most patients (mean +/- standard
      error of the mean pain score: 2.35 +/- 0.19). Higher pain was seen midprocedure
      versus at the beginning (p < 0.0001) and at the end (p = 0.003) of PDT. There was
      no significant difference in pain perception between genders and different
      treatment areas. CONCLUSIONS: Our results provide evidence that red light ALA PDT
      of AKs is very well tolerated with the two-step irradiance protocol.

PMID- 29227200
TI  - Telepsychiatry for Children and Adolescents: A Review of the PROMETTED Project.
AB  - BACKGROUND: Telemedicine for children and adolescents is a public health topic,
      and since 2009 in France, the legal framework defines practical modalities. Some
      children with Attention Deficit with or without Hyperactivity Disorder, social
      anxiety, or Autism Spectrum Disorder (ASD) can be easily engaged within a
      teleconsultation model. Literature suggests new opportunities to facilitate the
      care process for the ASD person and his family: diagnosis with the use of
      validated instruments and parental accompaniment. METHODS: Since 2015, a pilot
      project called PROMETTED was supported by the Regional Health Agency of Ile de
      France. It was developed and managed by the team of the Center for Diagnosis and
      Evaluation for Autism (CDEA) of Sainte-Anne Hospital and associated PEDIATED, the
      CDEA of Versailles. RESULTS: Five medico-social structures for children and
      adolescents with ASD and the two CDEAs co-elaborated a scheme of intervention
      with telemedicine. The remote evaluation is a four-step process structured around
      the medical history and the observation of the young subject; the Autism
      Diagnostic Interview; the use of the Childhood Autism Rating Scale and the
      Vineland Adaptive Behavior Scales; and feedback to parents. CONCLUSIONS: Medico
      economic and satisfaction evaluations are in progress.

PMID- 29227201
TI  - Early Rescue from Acute Severe Clostridium Difficile: A Novel Treatment Strategy.
AB  - BACKGROUND: Severe Clostridium difficile infections (CDI) can lead to significant
      impediments to effective treatment. We developed a novel treatment protocol
      utilizing bedside gastrointestinal lavage (GIL) for the management of patients
      with severe, complicated CDI. We describe the development and early outcomes of
      non-operative bedside GIL in hospitalized patients with severe, complicated CDI
      following the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL)
      framework at the Idea stage. We compared our results with those of a cohort of
      patients managed with colectomy. METHODS: We conducted a retrospective cohort
      study of hospitalized patients with severe, complicated CDI who failed
      conventional medical therapy and were referred for surgical consultation at two
      academic tertiary-care hospitals between January 2009 and January 2015. After
      surgical assessment, the attending surgeon decided to proceed either with bedside
      GIL or directly to colectomy. Bedside GIL involved nasojejunal tube insertion
      followed by flushing with 8 L of polyethylene glycol 3350/electrolyte solution
      over 48 h. Both patient groups received standard medical treatment with
      vancomycin 500 mg q 6 h enterally and metronidazole 500 mg intravenously three
      times daily for 14 d. The main outcomes of interest were the incidence of
      colectomy, complications, and mortality rate. RESULTS: Nineteen and seventeen
      patients underwent GIL and direct colectomy, respectively. There were no
      significant differences between the groups in terms of demographics, American
      Society of Anesthesiologists class, disease severity, need for intensive care
      unit admission, mechanical ventilation, vasopressor use, serum lactate
      concentration, or proportion presenting with hypotension, acute kidney injury, or
      a white blood cell count >16,000/mcL or <4,000/mcL (p > 0.1). The in-hospital
      mortality rate was 26% (5/19) and 41% (7/17) for the GIL and colectomy groups,
      respectively (p = 0.35). Only one patient in the GIL group failed the protocol,
      requiring colectomy. There were no significant differences in complications in
      the two groups. CONCLUSIONS: Bedside GIL appeared to be safe for the treatment of
      patients with severe, complicated CDI who had failed conventional medical
      therapy. It did not appear to increase the risk of morbidity or death compared
      with the traditional strategy of proceeding directly to colectomy.

PMID- 29227202
TI  - Challenges of Vaccine Development for Zika Virus.
AB  - The emergence of outbreaks of Zika virus (ZIKV) in Brazil in 2015 was associated
      with devastating effects on fetal development and prompted a world health
      emergency and multiple efforts to generate an effective vaccine against
      infection. There are now more than 40 vaccine candidates in preclinical
      development and six in clinical trials. Despite similarities with other
      flaviviruses to which successful vaccines have been developed, such as yellow
      fever virus and Japanese Encephalitis virus, there are unique challenges to the
      development and clinical trials of a vaccine for ZIKV.

PMID- 29227203
TI  - Therapeutic charm of quercetin and its derivatives: a review of research and
      patents.
AB  - Bioactive polyphenolic compounds derived from plants are being utilized for
      prevention of various chronic diseases including cancer and cardiovascular
      disorders. Quercetin, a potential poly-phenolic flavonol, found in onions, apples
      and berries, has been implicated against cancer proliferation, chronic
      inflammation and various other oxidative manifestations. Evidences suggested that
      quercetin negatively regulates the numerous crucial signaling pathways associated
      with life-threatening diseases. Major signaling pathways including NF-kappaB,
      MAPK, PI3K-AKT and mTOR are found to be regulated by quercetin. In addition,
      several patents have reported recently on quercetin derivatives describing wide
      therapeutic applications such as anticancer/antiproliferatory,
      antioxidative/antiaging, antiviral, anti-inflammatory, cardioprotective. Present
      review emphasizes the chemistry and sources of quercetin followed by description
      of its broad-spectrum therapeutic potential along with proposed mechanisms of
      action. Furthermore, this review also highlights the important modifications in
      the basic chemical structure of quercetin in terms of published patents.
      Insolubility of the bioactive compounds restricts their medicinal importance
      which could be overcome by modifications in the chemical structure of so-called
      derivatives. Most of the patents deal with the modifications in chemical
      structure of quercetin mainly at hydroxyl groups and C-6 and C-7 positions.

PMID- 29227204
TI  - Canada's Supreme Court abolishes 'promise of the patent'.
AB  - The Supreme Court of Canada has done away with the 'promise of the patent'
      doctrine. This doctrine invalidated patents to numerous otherwise useful
      inventions from 2005 to 2016. The Supreme Court of Canada has clarified that the
      statutory utility requirement requires only a scintilla of utility related to the
      subject matter of the invention. This utility must have been demonstrated or
      soundly predicted as of the Canadian filing date. The decision brings increased
      certainty to Canada's patent system and more closely aligns it with international
      norms.

PMID- 29227205
TI  - Sexual violence against men and boys in conflict and forced displacement:
      implications for the health sector.
AB  - Sexual violence against men and boys is commonplace in many conflict-affected
      settings and may be frequent in relation to forced displacement as well.
      Adolescent boys, forming the majority of unaccompanied minors globally, are a
      particularly vulnerable group. Yet sensitised health services for adult and
      adolescent male sexual violence survivors are scarce, and barriers to accessing
      care remain high. We describe current challenges and gaps in the provision of
      health care for male survivors in settings affected by conflict and forced
      displacement, and provide suggestions on how to improve service provision and
      uptake.

PMID- 29227206
TI  - Attitudes Toward e-Health: The Otolaryngologists' Point of View.
AB  - INTRODUCTION: Online communication and the number of e-health applications have
      noticeably increased. However, little is known about the otolaryngologists' use
      behavior and their attitudes toward the potential of e-health. The aims of the
      study were to evaluate the documentation, information, and communication
      technologies used by otolaryngologists and to get a better understanding of their
      attitudes toward the potential of e-health for cross-sectoral patient care.
      METHODS: A survey was developed and tested by otolaryngologists, healthcare
      information technology experts, and health services researchers. A total of 334
      otolaryngologists in private practice were asked to participate in this cross
      sectional study. In total, 234 of them took part in the study, and 157 returned
      completed questionnaires. Statistical analysis was performed by using crosstabs,
      including chi-square tests, and multivariate logistic regressions. Results and
      Materials: Digital technologies are widely used by otolaryngologists (e.g., 89.6%
      use an electronic health record). However, the majority of intersectoral
      communication is still based on analogue techniques (e.g., fax use in 63.7%).
      From the otolaryngologists' perspectives, the potential of e-health for
      intersectoral care is mostly in appointment scheduling, further referrals to
      hospitals, and automated appointment reminders. The physicians' attitudes toward
      e-health are associated with their Internet use behavior in daily life (odds
      ratio = 4.30, confidence interval 1.11-16.64, p = 0.035) but not with their
      demographics. DISCUSSION: The otolaryngologists are well prepared and have an
      overall positive attitude toward e-health for deeper use in cross-sectoral care.
      Therefore, e-health in otolaryngology needs more attention and resources for
      further studies, especially with a focus on quality and safety of care.

PMID- 29227207
TI  - Photobiomodulation: How Many Sessions and How Often?

PMID- 29227208
TI  - Zika virus - the glamour of a new illness, the practical abandonment of the
      mothers and new evidence on uncertain causality.

PMID- 29227209
TI  - Simultaneous determination of organochlorine and pyrethriod pesticide residues in
      the Chinese patent medicines by gas chromatography-tandem mass spectrometry.
AB  - A simple, sensitive, reliable method was developed for the simultaneous
      determination of organochlorine and pyrethriod pesticide residues in Chinese
      patent medicines Six ingredient rehmannia pills and Xiaoyao pills. These
      pesticides were extracted by ethyl acetate. The extraction time and volume of
      ethyl acetate were optimized. Cleanup of extracts was performed with dispersive
      solid phase extraction using graphitized carbon black as the sorbent. The
      determination of pesticides in the final extracts was carried out by gas
      chromatography-tandem mass spectrometry in multiple reaction monitoring mode (GC
      MS/MS, MRM). The linearity of the calibration curves is good in matrix-matched
      standard and yields the coefficients of determination (R2) >=0.99 for all of the
      target analytes. Under optimized conditions, the average recoveries (five
      replicates) for most pesticides range from 75.5% to 114.6%, and RSDs are less
      than 10.0%. The LODs of 18 pesticides in Six ingredient rehmannia pill and
      Xiaoyao pills are in the range of 0.01-8.82 MUg kg-1. The developed method meets
      the requirements of pesticide residue analysis and could be effectively used for
      routine analysis of the organochlorine and pyrethriod pesticide residues in Six
      ingredient rehmannia pills and Xiaoyao pills.

PMID- 29227210
TI  - Separate roles for chromatin and lamins in nuclear mechanics.
AB  - The cell nucleus houses, protects, and arranges the genome within the cell.
      Therefore, nuclear mechanics and morphology are important for dictating gene
      regulation, and these properties are perturbed in many human diseases, such as
      cancers and progerias. The field of nuclear mechanics has long been dominated by
      studies of the nuclear lamina, the intermediate filament shell residing just
      beneath the nuclear membrane. However, a growing body of work shows that
      chromatin and chromatin-related factors within the nucleus are an essential part
      of the mechanical response of the cell nucleus to forces. Recently, our group
      demonstrated that chromatin and the lamina provide distinct mechanical
      contributions to nuclear mechanical response. The lamina is indeed important for
      robust response to large, whole-nucleus stresses, but chromatin dominates the
      short-extension response. These findings offer a clarifying perspective on varied
      nuclear mechanics measurements and observations, and they suggest several new
      exciting possibilities for understanding nuclear morphology, organization, and
      mechanics.

PMID- 29227211
TI  - Babesia Occurrence in Rodents in Relation to Landscapes of Mainland Southeast
      Asia.
AB  - The purpose of this study is to investigate the relationships between habitat
      structure and Babesia spp. occurrence in rodents in mainland Southeast Asia. Of
      1439 rodents and insectivores investigated, the protist Babesia was found in only
      81 individuals (5.6% of the micromammals investigated) with Babesia microti U.S.
      type the more prevalent (4.1%), followed by the B. microti Kobe type (1.2%), and
      by the very rare Babesia BiCM002 (0.04%). We used georeferenced data of rodents
      analyzed for Babesia infection and land cover maps produced for the seven study
      sites in Thailand, Cambodia, and Lao PDR, where they were collected. Rodents
      infected by Babesia were more likely to be found in settlements close to forested
      areas, which may represent risky place for spillover of Babesia species to
      humans.

PMID- 29227212
TI  - Screening for host proteins interacting with Escherichia coli O157:H7 EspF using
      bimolecular fluorescence complementation.
AB  - AIM: To screen host proteins that interact with enterohemorrhagic Escherichia
      coli O157:H7 EspF. MATERIALS & METHODS: Flow cytometry and high-throughput
      sequencing were used to screen interacting proteins. Molecular function,
      biological processes and Kyoto Encyclopedia of Genes and Genomes pathways were
      studied using the DAVID online tool. Glutathione S-transferase pull down and dot
      blotting were used to verify the interactions. RESULTS: 293 host proteins were
      identified to associate with EspF. They were mainly enriched in RNA splicing (p =
      0.005), ribosome structure (p = 0.012), and involved in 109 types of signaling
      pathways. SNX9 and ANXA6 were confirmed to interact with EspF. CONCLUSION: EspF
      interacts with ANXA6; they may form a complex to manipulate the process of
      phagocytosis; EspF plays a highlighted pathogenic role in enterohemorrhagic E.
      coli infection process.

PMID- 29227214
TI  - Human reliability assessment in a 99Mo/99mTc generator production facility using
      the standardized plant analysis risk-human (SPAR-H) technique.
AB  - INTRODUCTION: Reducing human error is an important factor for enhancing safety
      protocols in various industries. Hence, analysis of the likelihood of human error
      in nuclear industries such as radiopharmaceutical production facilities has
      become more essential. METHODS: This cross-sectional descriptive study was
      conducted to quantify the probability of human errors in a 99Mo/99mTc generator
      production facility in Iran. First, through expert interviews, the production
      process of the 99Mo/99mTc generator was analyzed using hierarchical task analysis
      (HTA). The standardized plant analysis risk-human (SPAR-H) method was then
      applied in order to calculate the probability of human error. RESULTS: Twenty
      tasks were determined using HTA. All of the eight performance shaping factors
      (PSFS) were evaluated for the tasks. The mean probability of human error was
      0.320. The highest and the lowest probability of human error in the 99Mo/99mTc
      generator production process, related to the 'loading the generator with the
      molybdenum solution' task and the 'generator elution' task, were 0.858 and 0.059,
      respectively. CONCLUSION: Required measures for reducing the human error
      probability (HEP) were suggested. These measures were derived from the level of
      PSFS that were evaluated in this study.

PMID- 29227213
TI  - Productive common light chain libraries yield diverse panels of high affinity
      bispecific antibodies.
AB  - The commercial success of bispecific antibodies generally has been hindered by
      the complexities associated with generating appropriate molecules for both
      research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG)
      based on two antibodies that use an identical common light chain can be combined
      with a minimal set of Fc mutations to drive heavy chain heterodimerization in
      order to address these challenges. However, the facile generation of common light
      chain antibodies with properties similar to traditional monoclonal antibodies has
      not been demonstrated and they have only been used sparingly. Here, we describe
      the design of a synthetic human antibody library based on common light chains to
      generate antibodies with biochemical and biophysical properties that are
      indistinguishable to traditional therapeutic monoclonal antibodies. We used this
      library to generate diverse panels of well-behaved, high affinity antibodies
      toward a variety of epitopes across multiple antigens, including mouse 4-1BB, a
      therapeutically important T cell costimulatory receptor. Over 200 BsIgG toward 4
      1BB were generated using an automated purification method we developed that
      enables milligram-scale production of BsIgG. This approach allowed us to identify
      antibodies with a wide range of agonistic activity that are being used to further
      investigate the therapeutic potential of antibodies targeting one or more
      epitopes of 4-1BB.

PMID- 29227216
TI  - Front-of-package nutrition references are positively associated with food
      processing.
AB  - OBJECTIVE: Foods characterized by a high degree of processing are pervasive in
      the global food supply and concerns have been raised about their contribution to
      the escalating burden of diet-related disease. It has been suggested that the
      dominance of these products relates in part to their aggressive on-package
      marketing. The purpose of the present study was to assess the relationship
      between the extent and nature of front-of-package (FOP) nutrition references on
      products sold in Canadian supermarkets and the level of food processing. DESIGN:
      FOP references were recorded from all packaged foods. Nutrition references were
      classified as 'negative' and 'positive' and further differentiated in terms of
      the use of regulated and unregulated text. Foods were coded for level of
      processing, using three different classification systems. Logistic and negative
      binomial regression analyses were conducted to assess associations. SETTING:
      Three large Toronto supermarkets, from the top Canadian food retailers. SUBJECTS:
      Packaged foods (n 20 520). RESULTS: Forty-one per cent of products had FOP
      nutrition references. Irrespective of the classification system considered, the
      most processed category comprised the greatest proportion of products and nearly
      half of these bore FOP references. Foods deemed most processed were more likely
      than less processed products to bear FOP references and regulated and unregulated
      references to negative ingredients, but they were equally or less likely to bear
      positive nutrition references, depending on the classification system.
      CONCLUSIONS: The greater frequency of FOP nutrition references on heavily
      processed foods raises questions about the extent to which discretionary FOP
      labelling supports public health efforts to promote healthy eating.

PMID- 29227215
TI  - Dietary phosphatidylcholine impacts on growth performance and lipid metabolism in
      adult Genetically Improved Farmed Tilapia (GIFT) strain of Nile tilapia
      Oreochromis niloticus.
AB  - This study aimed to determine the effects of supplementing the diet of adult Nile
      tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth
      performance, body composition, fatty acid composition and gene expression.
      Genetically Improved Farmed Tilapia fish with an initial body weight of 83.1 (sd
      2.9) g were divided into six groups. Each group was hand-fed a semi-purified diet
      containing 1.7 (control diet), 4.0, 6.5, 11.5, 21.3 or 41.0 g PC/kg diet for 68
      d. Supplemental PC improved the feed efficiency rate, which was highest in the
      11.5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary
      PC increased PC content in the liver and decreased crude fat content in the
      liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with
      increasing dietary PC. Cytoplasmic phospholipase A 2 and secreted phospholipase A
      2 mRNA expression were up-regulated in the brain and heart in PC-supplemented
      fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral
      tissue but increased expression in muscle. Hormone-sensitive lipase and
      lipoprotein lipase expression increased in the liver with increasing dietary PC.
      Growth hormone mRNA expression was reduced in the brain and insulin-like growth
      factor-1 mRNA expression in liver reduced with PC above 6.5 g/kg. Our results
      demonstrate that dietary supplementation with PC improves feed efficiency and
      reduces liver fat in adult Nile tilapia, without increasing weight gain,
      representing a novel dietary approach to reduce feed requirements and improve the
      health of Nile tilapia.

PMID- 29227217
TI  - Public Health Nutrition special issue on ultra-processed foods.

PMID- 29227218
TI  - Association between sequevar and antibiotic treatment outcome in patients with
      Mycobacterium abscessus complex infections in Japan.
AB  - PURPOSE: Macrolide susceptibility differs between subspecies in the Mycobacterium
      abscessus complex, likely due to differences in erm(41) sequevars. Patients with
      M. abscessus complex infection generally show poor clinical outcomes in response
      to antibiotic treatment. Here, the association between genotype and treatment
      outcome was investigated. METHODOLOGY: We collected 69 isolates from 35 patients
      with non-cystic fibrosis bronchiectasis: 24 had M. abscessus complex lung disease
      and non-cystic fibrosis bronchiectasis, and 11 were colonized. Outcome analysis
      was performed in the 24 infected patients. Molecular analyses, including erm(41)
      and rrl sequencing, and variable-number tandem-repeat (VNTR) analysis of 69
      isolates, from 24 infected and 11 colonized patients, were performed to elucidate
      the influence of genotype on antibiotic susceptibility. RESULTS: Among the 24
      patients, 18 (14 infected with M. abscessus subsp. abscessus and 4 with M.
      abscessus subsp. massiliense) showed unfavourable outcomes; six (three infected
      with M. abscessus subsp. abscessus and three with M. abscessus subsp.
      massiliense) exhibited favourable outcomes. Patients with unfavourable outcomes
      showed acquired clarithromycin resistance (33.3 vs 0 %), mixed sequevars (38.9 vs
      16.7 %) and differing VNTR patterns between initial and serial isolates (33.3 vs
      16.7 %). In contrast, in the 11 colonized patients, M. abscessus subsp. abscessus
      C28 (sequevar 02) and M. abscessus subsp. massiliense were the most prevalent
      subspecies. CONCLUSION: Patients infected with multiple sequevars and genotypes
      were more likely to exhibit treatment failure and/or recurrence. The precise
      identification of subspecies and analyses of mycobacterial characteristics may
      help to predict treatment outcomes in patients with M. abscessus complex lung
      disease.

PMID- 29227220
TI  - Taxonomic analyses of members of the Streptomyces cinnabarinus cluster,
      description of Streptomyces cinnabarigriseus sp. nov. and Streptomyces
      davaonensis sp. nov.
AB  - Roseoflavin is the only known riboflavin (vitamin B2) analog with antibiotic
      properties. It is actively taken up by many micro-organisms and targets
      flavinmononucleotide riboswitches and flavoproteins. It is described as the
      product of the tentatively named 'Streptomyces davawensis' JCM 4913. Taxonomic
      analysis of this strain with a polyphasic approach showed that it is very closely
      related to Streptomyces cinnabarinus (DSM 40467). The two Streptomyces isolates
      were obtained from different geographical locations (the Philippines and the
      Kamchatka Peninsula, respectively), their genomes have been sequenced and the
      question was whether or not the two isolates were representatives of the same
      species. As we also worked with another isolate of Streptomyces cinnabarinus JS
      360, the producer of the cinnabaramides, we wanted to clarify the taxonomic
      position of the three isolates by using a polyphasic approach. After analysis of
      the 16S rRNA gene sequence, we found in total 23 species of the genus
      Streptomyces that showed a similarity higher than 98.5 % to the three strains. We
      showed that 'S. davawensis' JCM 4913 and S. cinnabarinus DSM 40467 were very
      closely related but belong to two different species. Hence, we validate 'S.
      davawensis' as Streptomyces davaonensis sp. nov. with the type strain JCM 4913T
      (=DSM 101723T). In addition, the cinnabaramide producer can be clearly
      differentiated from S. davaonensis and this isolate is described as Streptomyces
      cinnabarigriseus sp. nov. with strain JS360T (=NCCB 100590T=DSM 101724T) as the
      type strain.

PMID- 29227219
TI  - Halorubrum aethiopicum sp. nov., an extremely halophilic archaeon isolated from
      commercial rock salt.
AB  - A novel extremely halophilic archaeon, designated SAH-A6T, was isolated from a
      sample of commercial rock salt in Ethiopia. Cells of SAH-A6T were aerobic and
      pleomorphic. The strain was able to grow at concentrations of 15-30 % (w/v) NaCl
      (optimum 20-25 % NaCl), at pH 6.0-9.0 (optimum pH 7.0) and in a temperature range
      of 30-55  degrees C (optimum 37-45  degrees C). Mg2+ was not required for growth
      of SAH-A6T cells. On the basis of 16S rRNA gene sequence analysis, strain SAH-A6T
      was closely related to Halorubrum halodurans Cb34T (99.1 %), Halorubrum rubrum
      YC87T (98.9 %), Halorubrum aquaticum EN-2T (98.7 %), Halorubrum cibi JCM 15757T
      (98.4 %), Halorubrum luteum CGSA15T (97.3 %), Halorubrum lipolyticum 9-3T (97.1
      %), Halorubrum tibetense 8W8T (97.1 %), Halorubrum kocurii JCM 1478T (97.1 %),
      Halorubrum halophilum B8T (97.0 %) and Halorubrum persicum C49T (97.0 %).
      Phylogenetic analysis based on the rpoB' gene sequences showed that strain SAH
      A6T was closely related to Hrr. halodurans Cb34T (99.7 %), Hrr. aquaticum JCM
      14031T (99.3 %) and other members of the genus Halorubrum (<99.0 %). The DNA G+C
      content of the strain was 68.0 mol%. DNA-DNA hybridization between strain SAH-A6T
      and the most closely related members of the genus Halorubrum were below 55 %,
      suggesting that the new isolate constitutes a different genospecies. On the bases
      of chemotaxonomic, phenotypic and genotypic data, strain SAH-A6T (=KCCM
      43215T=JCM 31519T) represents a novel species of the genus Halorubrum, for which
      the name Halorubrumaethiopicum sp. nov. is proposed.

PMID- 29227221
TI  - An Alcohol Policy Trifecta: Reduce Alcohol Problems, Save on Health Care,
      Generate Public Revenues.

PMID- 29227223
TI  - Close Ranks: Understanding the Relevance of Ethnicity- and Race-Based Alcohol
      Disparities for Other Marginalized Subpopulations-A Commentary on Zemore et al.
      (2018).

PMID- 29227224
TI  - Considerations of Socioeconomic Status as Separate From Race: A Commentary on
      Zemore et al. (2018).

PMID- 29227225
TI  - Commentary on Zemore et al. (2018): The Future of Alcohol-Related Health
      Disparities Research in the United States.

PMID- 29227226
TI  - An Outstanding Plan of Attack, But How Do We Fund It? A Commentary on Zemore et
      al. (2018).

PMID- 29227222
TI  - The Future of Research on Alcohol-Related Disparities Across U.S. Racial/Ethnic
      Groups: A Plan of Attack.
AB  - OBJECTIVE: Research suggests striking disparities in alcohol use, problems, and
      treatment across racial/ethnic groups in the United States. However, research on
      alcohol-related disparities affecting racial/ethnic minorities remains in its
      developmental stages. The current article aims to support future research in this
      growing field by highlighting some of the most important findings, questions, and
      approaches, focusing on psychosocial research. METHOD: This article advances
      seven research needs (i.e., questions and topics meriting attention) that we
      believe are of crucial importance to the field. We draw on the existing
      literature to illuminate under-explored areas that are highly relevant to health
      intervention and that complement the field's existing focus. RESULTS: Identified
      research needs include research that (a) better describes disparities in alcohol
      related health conditions and their drivers, (b) identifies appropriate screening
      and brief intervention methods for racial/ethnic minorities, (c) investigates
      disparities in access to and use of alcohol treatment and support services, (d)
      examines the comparative efficacy of existing alcohol interventions and develops
      tailored interventions, (e) explores the impacts of specific alcohol policies
      across and within racial/ethnic groups, and (f) describes the full spectrum of
      alcohol-related harms and how and why these may vary across racial/ethnic groups.
      We also call for (g) continuing research to monitor disparities over time.
      CONCLUSIONS: This article points to specific strategies for describing,
      explaining, intervening on, and monitoring some of the most substantial alcohol
      related disparities. Conclusions outline methods and processes that may be
      advantageous in addressing these priorities, including the use of longitudinal
      designs; consideration of life course changes; attention to nontraditional
      intervention settings; and inclusion of disadvantaged populations in all aspects
      of research.

PMID- 29227228
TI  - Back to the Future . . . or . . . Is That All There Is? A Commentary on Courtney
      et al. (2018).

PMID- 29227229
TI  - Brain Reward Responses Are Behaviorally Relevant: The Authors Respond.

PMID- 29227227
TI  - Reward System Activation in Response to Alcohol Advertisements Predicts College
      Drinking.
AB  - OBJECTIVE: In this study, we assess whether activation of the brain's reward
      system in response to alcohol advertisements is associated with college drinking.
      Previous research has established a relationship between exposure to alcohol
      marketing and underage drinking. Within other appetitive domains, the
      relationship between cue exposure and behavioral enactment is known to rely on
      activation of the brain's reward system. However, the relationship between neural
      activation to alcohol advertisements and alcohol consumption has not been studied
      in a nondisordered population. METHOD: In this cross-sectional study, 53 college
      students (32 women) completed a functional magnetic resonance imaging scan while
      viewing alcohol, food, and control (car and technology) advertisements.
      Afterward, they completed a survey about their alcohol consumption (including
      frequency of drinking, typical number of drinks consumed, and frequency of binge
      drinking) over the previous month. RESULTS: In 43 participants (24 women) meeting
      inclusion criteria, viewing alcohol advertisements elicited activation in the
      left orbitofrontal cortex and bilateral ventral striatum-regions of the reward
      system that typically activate to other appetitive rewards and relate to
      consumption behaviors. Moreover, the level of self-reported drinking correlated
      with the magnitude of activation in the left orbitofrontal cortex. CONCLUSIONS:
      Results suggest that alcohol cues are processed within the reward system in a way
      that may motivate drinking behavior.

PMID- 29227230
TI  - Erosion of State Alcohol Excise Taxes in the United States.
AB  - OBJECTIVE: In the United States, excessive alcohol consumption is responsible for
      88,000 deaths annually and cost $249 billion, or $2.05 per drink, in 2010.
      Specific excise taxes, the predominant form of alcohol taxation in the United
      States, are based on the volume of alcohol sold rather than a percentage of price
      and can thus degrade over time because of inflation. The objective of this study
      was to describe changes in inflation-adjusted state alcohol excise taxes on a
      beverage-specific basis. METHOD: State-level data on specific excise taxes were
      obtained from the Alcohol Policy Information System and the Tax Foundation.
      Excise tax rates were converted into the tax per standard U.S. drink (14 g of
      ethanol) for beer, wine, and distilled spirits, and converted into 2015 dollars
      using annual Consumer Price Index data. RESULTS: Across U.S. states, the average
      state alcohol excise tax per drink in 2015 was $0.03 for beer, $0.05 for
      distilled spirits, and $0.03 for wine. From 1991 to 2015, the average inflation
      adjusted (in 2015 dollars) state alcohol excise tax rate declined 30% for beer,
      32% for distilled spirits, and 27% for wine. Percentage declines in state excise
      taxes since their inception were more than twice as large as those from 1991 to
      2015. CONCLUSIONS: In 2015, average state specific excise taxes were $0.05 or
      less per standard drink across all beverage types and have experienced
      substantial inflation-adjusted declines.

PMID- 29227231
TI  - Alcohol Policy Relevant Indicators and Alcohol Use Among Adolescents in Latin
      America and the Caribbean.
AB  - OBJECTIVE: This study assessed four alcohol policy indicators and their
      associations with adolescent alcohol use in Latin America and the Caribbean.
      METHOD: A secondary data analysis of nationally representative, cross-sectional
      data sets (years 2007-2013) from 26 Latin American and Caribbean countries was
      performed (N = 55,248 13- to 15-year-old students). Logistic regression models
      were used to analyze associations between alcohol policy relevant indicators and
      alcohol use, adjusting for the country and demographic variables. RESULTS: In all
      countries, at least 20% of the students were exposed to alcohol advertisements
      daily or almost daily, which was associated with a twofold increased risk of
      current alcohol use and at least monthly heavy drinking. Obtaining alcohol from a
      shop was associated with a nearly threefold increased risk of at least monthly
      heavy drinking compared with obtaining alcohol from home, which was the most
      common way to obtain alcohol. Being denied from purchasing retail alcohol was
      associated with a decreased risk of at least monthly heavy drinking. About 27% to
      53% of the students who had tried to purchase alcohol had been denied. One in
      four students reported exposure to drink driving in the past 30 days.
      CONCLUSIONS: Deficits in alcohol policy indicators were identified in a number of
      countries. Improving implementation and enforcement of alcohol policies could
      reduce alcohol use and related burden among adolescents in a number of Latin
      American and Caribbean countries.

PMID- 29227232
TI  - Alcohol Consumption and the Physical Availability of Take-Away Alcohol:
      Systematic Reviews and Meta-Analyses of the Days and Hours of Sale and Outlet
      Density.
AB  - OBJECTIVE: Systematic reviews and meta-analyses were completed studying the
      effect of changes in the physical availability of take-away alcohol on per capita
      alcohol consumption. Previous reviews examining this topic have not focused on
      off-premise outlets where take-away alcohol is sold and have not completed meta
      analyses. METHOD: Systematic reviews were conducted separately for policies
      affecting the temporal availability (days and hours of sale) and spatial
      availability (outlet density) of take-away alcohol. Studies were included up to
      December 2015. Quality criteria were used to select articles that studied the
      effect of changes in these policies on alcohol consumption with a focus on
      natural experiments. Random-effects meta-analyses were applied to produce the
      estimated effect of an additional day of sale on total and beverage-specific
      consumption. RESULTS: Separate systematic reviews identified seven studies
      regarding days and hours of sale and four studies regarding density. The majority
      of articles included in these systematic reviews, for days/hours of sale (7/7)
      and outlet density (3/4), concluded that restricting the physical availability of
      take-away alcohol reduces per capita alcohol consumption. Meta-analyses studying
      the effect of adding one additional day of sale found that this was associated
      with per capita consumption increases of 3.4% (95% CI [2.7, 4.1]) for total
      alcohol, 5.3% (95% CI [3.2, 7.4]) for beer, 2.6% (95% CI [1.8, 3.5]) for wine,
      and 2.6% (95% CI [2.1, 3.2]) for spirits. The small number of included studies
      regarding hours of sale and density precluded meta-analysis. CONCLUSIONS: The
      results of this study suggest that decreasing the physical availability of take
      away alcohol will decrease per capita consumption. As decreasing per capita
      consumption has been shown to reduce alcohol-related harm, restricting the
      physical availability of take-away alcohol would be expected to result in
      improvements to public health.

PMID- 29227234
TI  - Could You Buy Me a Beer? Measuring Secondary Supply of Alcohol in Dutch On
      Premise Outlets.
AB  - OBJECTIVE: Alcohol is largely available for Dutch minors through on-premise
      secondary supply, which occurs when an adult furnishes an alcoholic drink to a
      minor in an on-premise outlet. Vendors allowing this secondary supply on their
      premises are in violation of the Dutch Licensing and Catering Act (legal age
      limit is 18 years old for the sale and possession of alcohol). Using existing
      mystery shopping protocols as a standard, our study objective was the development
      and field testing of a novel procedure, measuring vendors' compliance with
      secondary supply. METHOD: Using a newly developed mystery shopping procedure,
      transfers of alcohol between young adult buyers and minors were staged in 109
      Dutch on-premise outlets (cafes and bars) to measure vendors' compliance with
      secondary supply. RESULTS: In accordance with the Dutch Licensing and Catering
      Act, 29% of the vendors disallowed the secondary supply of alcohol to minors (32
      of 109 attempts). During 40 attempts (of 109 attempts; 37%), the vendor asked for
      the identification document (ID) of the minor. Compliance after the ID was
      requested was 80% (32 of 40 attempts). During 8 attempts (20%), the minors were
      served even after the ID of the minor was requested. CONCLUSIONS: Mystery
      shopping is a suitable methodology for measuring compliance with secondary
      supply. Results show that alcohol is largely available for Dutch minors through
      secondary supply. Governments that intend to formulate and evaluate enforcement
      policies aimed at curbing high alcohol availability for minors are advised to use
      this novel procedure for monitoring compliance and to use these results for
      agenda setting and benchmarking.

PMID- 29227233
TI  - Examination of Cross-Sectional Associations of Neighborhood Deprivation and
      Alcohol Outlet Density With Hazardous Drinking Using a Twin Design.
AB  - OBJECTIVE: The purpose of this study was to examine whether neighborhood
      socioeconomic deprivation and alcohol outlet density are associated with
      hazardous drinking using a co-twin design to control for confounding because of
      genetic and shared environmental factors. METHOD: The study sample included cross
      sectional data from 1,996 same-sex adult twin pairs (mean age = 36.6; 65.9%
      female) from the Washington State Twin Registry. The Singh Index was used to
      characterize neighborhood social deprivation for participants' census tract of
      residence. Geocoded alcohol outlet data were used to create a measure of census
      tract alcohol outlet density. The three-item Alcohol Use Disorders Identification
      Test-Consumption scale (AUDIT-C) was used to measure the level of hazardous
      drinking. Poisson mixed-effects models were used to examine associations between
      neighborhood factors and AUDIT-C score. Covariates included household income,
      level of education completed, non-White race, sex, and rurality of residence.
      RESULTS: Accounting for covariates, there was a statistically significant within
      pair association between neighborhood socioeconomic deprivation and a higher
      level of hazardous drinking. There was no within-pair association between the
      density of alcohol outlets and hazardous drinking. Associations did not differ by
      zygosity. CONCLUSIONS: The socioeconomic conditions of the neighborhood may play
      an important role in the development of alcohol misuse even after accounting for
      genetic and shared environmental influences. Twin designs may be a promising
      complementary approach to investigating the role of neighborhood characteristics
      on alcohol and substance use. Further research is needed to better understand the
      ways through which and for whom neighborhood characteristics may influence
      hazardous drinking.

PMID- 29227235
TI  - Drinking Motives and Alcohol Use: The SERVe Study of U.S. Current and Former
      Service Members.
AB  - OBJECTIVE: Hazardous drinking in the armed forces is a significant problem.
      Alcohol use motivations, known risk factors for problem drinking, have been
      underexplored in this population. Our study extends knowledge about drinking
      motives among current and former U.S. service members and provides
      recommendations on their utility in identifying alcohol-related problems by
      examining the factor structure of multidimensional drinking motives and their
      association to alcohol use. METHOD: Post-9/11 separated service members and
      current reservists were recruited from 35 Oregon employers to participate in a
      workplace study of supervisor support. The resulting sample (N = 509; 84% male;
      mean age = 39) completed a baseline assessment, which included a comprehensive
      drinking motives assessment. RESULTS: Drinkers comprised 88% of the sample, with
      a mean Alcohol Use Disorders Identification Test (AUDIT) score of 5.4 (SD = 4.6);
      23.9% scored 8 or more. The four-factor structure of the Drinking Motives
      Questionnaire-Revised, short form (DMQ-R-SF) was affirmed through confirmatory
      factor analysis. Internal drinking motives related to enhancement (positive) and
      coping (negative) were most predictive of alcohol use; coping motives were
      uniquely predictive of alcohol-related problems, when drinking
      quantity/frequency, as well as psychological distress, were controlled for.
      Coping motives also mediate the relationship between psychological distress and
      AUDIT scores. Results thus demonstrated the generalizability of the DMQ-R-SF
      motives measure for use with separated service members and reservists.
      CONCLUSIONS: Drinking motives, assessed by the DMQ-R-SF, represent reliable and
      important predictors of drinking and associated problems among service members.
      Inclusion of motivated drinking questions may enhance screening for alcohol
      related problems among current and former service members.

PMID- 29227236
TI  - Use of Marijuana and Other Substances Among Pregnant and Parenting Women With
      Substance Use Disorders: Changes in Washington State After Marijuana
      Legalization.
AB  - OBJECTIVE: In 2012, possession of marijuana for nonmedical use was legalized in
      Washington State. This study examined how legalization affected alcohol and drug
      use in a sample of pregnant and parenting women with substance use disorders.
      METHOD: Study participants from nine counties in Washington State (N = 1,359)
      were questioned about their substance use after completing a 3-year case
      management intervention program. The sample was divided into two cohorts based on
      whether participants had completed the program before or after legalization.
      RESULTS: Most study participants reported complete abstinence from alcohol and
      nonprescription drugs at program exit. Among those who were still using
      substances, women who completed the intervention after marijuana legalization
      were significantly more likely to report marijuana use at program exit compared
      with women who completed the intervention before marijuana legalization. Across
      both cohorts (pre- and post-legalization), we found a positive association of
      exit marijuana use with alcohol, illegal methadone, other opioids, amphetamines,
      and cocaine use; even when we controlled for historical period, the association
      with some of these substances with marijuana use remained evident. Independent of
      marijuana use, we saw increased use during the post-legalization period of
      alcohol, illicit methadone, and other opioids. CONCLUSIONS: Marijuana use at exit
      from the Parent-Child Assistance Program (PCAP) increased significantly after
      marijuana legalization in the state. Women who were not abstinent from marijuana
      at program exit were likely to report use of other substances as well. Our study
      design demonstrates an association but does not allow us to conclude that
      marijuana use leads to other substance use among this sample of women with a
      history of polysubstance use.

PMID- 29227237
TI  - Sexual Orientation Self-Concept Ambiguity and Alcohol Use Disorder Symptomology:
      The Roles of Motivated Psychological Distancing and Drinking to Cope.
AB  - OBJECTIVE: Women whose sexual identity is not exclusively heterosexual are at
      risk for alcohol use disorder (AUD) and problematic drinking. A textual analytic
      approach focusing on motivated psychological distancing in language style use was
      used to detect sexual minority women who are at greatest risk for an AUD. METHOD:
      Young adult women (N = 254) were asked to complete a self-report measure of
      sexual orientation self-concept ambiguity as well as free-write about their
      sexuality. In addition, they completed a questionnaire assessing AUD symptoms
      according to criteria from the Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition. The Linguistic Inquiry and Word Count (LIWC) program
      assessed language markers within participant-written essays that reflected acute
      states of aversive self-focus (i.e., fewer first-person pronouns, fewer present
      tense verbs). RESULTS: Drinking to cope with negative affectivity mediated the
      relationship between sexual orientation self-concept ambiguity and AUD
      symptomology. This indirect effect was conditional, moderated by higher use of
      language reflecting motivated psychological distancing, such that the indirect
      effect was significant only for women whose writing included fewer instances of
      first-person pronouns and present-tense verbs (-1 SD) compared with those with
      greater instances of first-person pronouns and present-tense verbs (+1 SD),
      reflecting motivated psychological distancing. CONCLUSIONS: Sexual minority women
      are at an increased risk for AUD. Further, this study suggests mechanisms that
      may exacerbate the relationship between sexual identity uncertainty and
      problematic drinking. The study presents a novel method of identifying
      individuals most at risk for alcohol misuse: detecting aversive self-focus in
      language style and word choice.

PMID- 29227238
TI  - Effects of Family Conflict and Anger on Alcohol Use Among American Indian
      Students: Mediating Effects of Outcome Expectancies.
AB  - OBJECTIVE: Identification of etiologic mechanisms underlying alcohol use among
      American Indian adolescents is essential because of higher rates of use and
      earlier initiation. One path links positive outcome expectancies to increased use
      for reduction of negative affect. This study estimates relationships between two
      aspects of distress among American Indian high school students-family conflict
      and anger-and alcohol involvement, and it investigates whether outcome
      expectancies serve as a mediator between these facets of distress and alcohol
      use. METHOD: Structural equation modeling evaluated study hypotheses among 975
      female and 936 male American Indian 9th- through 12th-grade students residing on
      or near reservations. Students were from 17 high schools recruited across six
      geographic regions where American Indians on reservations reside. Separate models
      were assessed for male and female students. RESULTS: Outcome expectancies
      mediated the relationship between both anger and family conflict for female
      students, but only for anger among male students. Full mediation was found for
      all significant effects. CONCLUSIONS: For female American Indian high school
      students, anger and family conflict operate in large degree through outcome
      expectancies for alcohol use. A similar effect is found for male students for
      anger.

PMID- 29227239
TI  - Couples' Alcohol Use in Middle and Later Life: Stability and Mutual Influence.
AB  - OBJECTIVE: Wives and husbands may influence one another's alcohol use, but little
      is known about within-couple patterns of alcohol consumption over time during
      midlife and later life. Drawing from a nationally representative U.S. sample of
      middle-aged and older married couples, we examined individual stability and
      partner influence in alcohol use across a 16-year period. METHOD: The analytic
      sample comprised 1,257 married couples age 40 and older who completed nine waves
      of the Health and Retirement Study (1996-2012). Dyadic multilevel models were
      estimated to simultaneously examine the stability of one's own alcohol use
      (number of drinks per occasion and per week) over time as well as whether partner
      drinking predicted subsequent alcohol use within couples. Models controlled for
      marital duration. RESULTS: Wives' and husbands' own prior alcohol use positively
      predicted alcohol use across waves, demonstrating individual stability in
      drinking patterns. Partners' alcohol use also positively predicted wives' and
      husbands' subsequent alcohol use, revealing partner influence in drinking
      patterns. Both stability and influence effects were stronger for husbands than
      for wives. CONCLUSIONS: This study provides evidence of stability and mutual
      influence in long-term patterns of alcohol use within mid- and late-life married
      couples. Findings highlight the interdependence between spouses and indicate that
      partners' drinking should be considered when examining men's and women's alcohol
      use over time.

PMID- 29227240
TI  - Pre-Drinking and the Temporal Gradient of Intoxication in a New Zealand Nightlife
      Environment.
AB  - OBJECTIVE: We measured changes in the average level of intoxication over time in
      the nighttime economy and identified the factors associated with intoxication,
      including pre-drinking. METHOD: A random intercept sample of 320 pedestrians (105
      women; 215 men) was interviewed and received breath alcohol analysis in the
      nighttime economy of Hamilton, New Zealand. Data were collected over a five-night
      period, between 7 P.M. and 2:30 A.M. Data were analyzed by plotting the moving
      average breath alcohol concentration (BrAC) over time and using linear regression
      models to identify the factors associated with BrAC. RESULTS: Mean BrAC was 241.5
      mcg/L for the full sample; 179.7 for women and 271.7 for men, which is a
      statistically significant difference. Mean BrAC was also significantly higher
      among those who engaged in pre-drinking than those who did not. In the regression
      models, time of night and pre-drinking were significantly associated with higher
      BrAC. The effect of pre-drinking on BrAC was larger for women than for men.
      CONCLUSIONS: The average level of intoxication increases throughout the night.
      However, this masks a potentially important gender difference, in that women's
      intoxication levels stop increasing after midnight, whereas men's increase
      continuously through the night. Similarly, intoxication of pre-drinkers stops
      increasing from 11 P.M., although remaining higher than non-pre-drinkers
      throughout the night. Analysis of BrAC provides a more nuanced understanding of
      intoxication levels in the nighttime economy.

PMID- 29227241
TI  - Nicotine Intake in Pregnant Smokers and a General Population of Smokers.
AB  - OBJECTIVE: The purpose of this study was to assess whether pregnant smokers have
      the same nicotine intake from cigarettes as a general population of smokers and
      whether the known lower daily cigarette consumption among pregnant smokers is
      associated with higher nicotine intake among pregnant smokers. METHOD: The study
      was a cross-sectional comparison of pregnant smokers and a general population of
      smokers in smoking cessation clinics. Participants were treatment-seeking
      pregnant (n = 476), nonpregnant female (n = 116), and male (n = 195) smokers who
      participated in two independent smoking cessation trials. Nicotine intake was
      measured as saliva cotinine/ cigarette/kg body weight ratio. RESULTS: The mean
      saliva cotinine (MUg/L)/ cigarette/kg body weight (0.21, SD = 0.15) of pregnant
      smokers was similar to that of nonpregnant female smokers (0.24, SD = 0.14) and
      higher than that of male smokers (0.18, SD = 0.12, p = .002) despite a
      substantially lower number of cigarettes per day (pregnant smokers: 12, SD = 6;
      nonpregnant female smokers: 26.6, SD = 11.7; male smokers: 23.5, SD = 9.5, p <
      .001). Among pregnant smokers, saliva cotinine, as expected, increased in
      parallel with the number of cigarettes per day, but nicotine intake
      (cotinine/cigarette/kg body weight) was inversely associated with daily cigarette
      consumption (p < .001). No association between cigarettes per day and nicotine
      intake was observed in male and nonpregnant female smokers (p = .43).
      CONCLUSIONS: This secondary analysis showed that pregnant smokers' nicotine
      intake was similar to that of a general population of smokers despite a lower
      cigarette consumption rate. Among pregnant smokers, lower daily cigarette
      consumption was associated with higher nicotine intake from cigarettes,
      suggesting compensatory smoking.

PMID- 29227242
TI  - Social Class and Alcohol Use by Youth: Different Drinking Behaviors, Different
      Associations?
AB  - OBJECTIVE: Low socioeconomic status (SES) is related to hazardous alcohol use in
      adults, and the association seems to be stronger for more deviant and harmful
      drinking behaviors. We examined whether a similar pattern was present among
      adolescents. METHOD: Data stem from a Norwegian school survey of 14- to 17-year
      olds (n = 12,966; response rate in participating schools: 86%). Parental
      education (high/ middle vs. low) was our main SES indicator. The outcomes
      comprised lifetime and past-year drinking and intoxication, and past-year
      symptoms of excessive drinking. We used Poisson regression to estimate relative
      risks (RR) and post-estimation Wald F tests to compare coefficient estimates.
      RESULTS: Parental education was related inversely to the lifetime measures of
      drinking and intoxication among all students but the 17-year-olds. The impact on
      any intoxication episodes was significantly stronger than that on any alcohol use
      only among the 14-year-olds (RR = 1.79, 95% CI [1.31, 2.43] vs. RR = 1.21, 95% CI
      [0.98, 1.49]) (p < .001). Among past-year drinkers at all ages (14-17 years; n =
      7,796), the differential impact of low parental education was particularly large
      with respect to the frequency of intoxication (RR = 1.68, 95% CI [1.39, 2.02])
      compared with the frequency of drinking (RR = 1.42, 95% CI [1.24, 1.62]) (p <
      .001) and frequent symptoms of excessive drinking (RR = 1.80, 95% CI [1.47,
      2.20]) compared with any symptoms (RR = 1.07, 95% CI [1.01, 1.14]) (p < .001). A
      similar but somewhat less clear pattern emerged when using an alternative
      indicator for low parental SES. CONCLUSIONS: Parents' social standing was
      inversely related to alcohol use by youth and related more strongly so to more
      deviant and harmful drinking behaviors.

PMID- 29227244
TI  - What Can We Learn From Alcohol-Related YouTube Videos?

PMID- 29227243
TI  - Cue Reactivity Essentials: Event-Related Potentials During Identification of
      Visual Alcoholic Stimuli in Social Drinkers.
AB  - OBJECTIVE: Cue reactivity is an automatic reaction to alcohol-related cues,
      contributing to the maintenance of drinking behavior and relapse in alcohol
      dependency. The identification of valid cue-reactivity features is a prerequisite
      for its clinical application. We were interested in the effects of visual
      features of alcohol cues (e.g., color) on cue reactivity. Assuming its
      development at a pre-pathological stage, we analyzed cue reactivity in heavy
      social drinkers, with light social drinkers as controls. We investigated whether
      cue reactivity was independent of visual features at an attentional (P100) and a
      motivational level (late positive potential, LPP). METHOD: Event-related
      potentials (ERPs; P100, LPP) were analyzed during a visual beverage
      classification task in heavy social drinkers and light social drinkers (N = 34
      university students). Photographs of beverages were classified as alcoholic or
      nonalcoholic. Two additional stimulus sets depicted unrecognizable scrambled
      visual information and recognizable black silhouettes of the original beverages.
      Analysis of contrast waves inferred content (unrecognized scrambled trials
      subtracted from original) and color information (recognized shape trials
      subtracted from original) during visual processing. Linear regression was used to
      predict Alcohol Use Disorders Identification Test (AUDIT) scores from ERPs.
      RESULTS: In heavy social drinkers, alcoholic-content LPP was increased and P100
      latency was shorter compared with nonalcoholic cues. Linear regression for
      alcohol content condition in the overall sample revealed shorter P100 latency and
      increased LPP amplitude predicting AUDIT scores. None of those effects were
      significant in the visual-feature control condition. CONCLUSIONS: Alcohol cue
      reactivity in heavy social drinkers was related to faster early attentional
      processes and motivational salience. The effect occurred independently of visual
      features in the pictures.

PMID- 29227245
TI  - Clearance of senescent decidual cells by uterine natural killer cells in cycling
      human endometrium.
AB  - In cycling human endometrium, menstruation is followed by rapid estrogen
      dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels
      activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal
      cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells
      that control embryo implantation. Here we show that FOXO1 also causes acute
      senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner.
      Selective depletion or enrichment of this subpopulation revealed that decidual
      senescence drives the transient inflammatory response associated with endometrial
      receptivity. Further, senescent cells prevent differentiation of endometrial
      mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15
      activated uterine natural killer (uNK) cells selectively target and clear
      senescent decidual cells through granule exocytosis. Our findings reveal that
      acute decidual senescence governs endometrial rejuvenation and remodeling at
      embryo implantation, and suggest a critical role for uNK cells in maintaining
      homeostasis in cycling endometrium.

PMID- 29227246
TI  - Tree crickets optimize the acoustics of baffles to exaggerate their mate
      attraction signal.
AB  - Object manufacture in insects is typically inherited, and believed to be highly
      stereotyped. Optimization, the ability to select the functionally best material
      and modify it appropriately for a specific function, implies flexibility and is
      usually thought to be incompatible with inherited behaviour. Here, we show that
      tree-crickets optimize acoustic baffles, objects that are used to increase the
      effective loudness of mate-attraction calls. We quantified the acoustic
      efficiency of all baffles within the naturally feasible design space using finite
      element modelling and found that design affects efficiency significantly. We
      tested the baffle-making behaviour of tree crickets in a series of experimental
      contexts. We found that given the opportunity, tree crickets optimised baffle
      acoustics; they selected the best sized object and modified it appropriately to
      make a near optimal baffle. Surprisingly, optimization could be achieved in a
      single attempt, and is likely to be achieved through an inherited yet highly
      accurate behavioural heuristic.

PMID- 29227247
TI  - Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in
      Drosophila melanogaster by phosphorylating acinus at serine437.
AB  - Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health.
      The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are
      still poorly understood. Here, we show that in Drosophila melanogaster Cdk5
      regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a
      targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily
      nuclear protein, which promotes starvation-independent, basal autophagy. Loss of
      Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas
      Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D
      mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal
      autophagy and lifespan are reduced, but restored to near wild-type levels in the
      presence of stabilized AcnS437D. Expression of aggregation-prone polyQ-containing
      proteins or the Amyloid-beta42 peptide, but not alpha-Synuclein, enhances Cdk5
      dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to
      maintain the protective role of basal autophagy in the initial responses to a
      subset of neurodegenerative challenges.

PMID- 29227248
TI  - Salt-inducible kinase 3 regulates the mammalian circadian clock by destabilizing
      PER2 protein.
AB  - Salt-inducible kinase 3 (SIK3) plays a crucial role in various aspects of
      metabolism. In the course of investigating metabolic defects in Sik3-deficient
      mice (Sik3-/-), we observed that circadian rhythmicity of the metabolisms was
      phase-delayed. Sik3-/- mice also exhibited other circadian abnormalities,
      including lengthening of the period, impaired entrainment to the light-dark
      cycle, phase variation in locomotor activities, and aberrant physiological
      rhythms. Ex vivo suprachiasmatic nucleus slices from Sik3-/- mice exhibited
      destabilized and desynchronized molecular rhythms among individual neurons. In
      cultured cells, Sik3-knockdown resulted in abnormal bioluminescence rhythms.
      Expression levels of PER2, a clock protein, were elevated in Sik3-knockdown cells
      but down-regulated in Sik3-overexpressing cells, which could be attributed to a
      phosphorylation-dependent decrease in PER2 protein stability. This was further
      confirmed by PER2 accumulation in the Sik3-/- fibroblasts and liver.
      Collectively, SIK3 plays key roles in circadian rhythms by facilitating
      phosphorylation-dependent PER2 destabilization, either directly or indirectly.

PMID- 29227250
TI  - ONCOPLASTIC SURGERY OF MULTICENTRIC (MULTIFOCAL) BREAST CANCER (CASE REPORT).
AB  - The multicentric/multifocal form of breast cancer has been considered as relative
      contraindicationfor breast conserving surgery. According to the results of the
      studies conducted in the last century, the local recurrence rate of the disease
      after breast conserving surgeries of multicentric/multifocal breast cancer
      exceeds 40%. Thus these data were considered as main argument for mastectomy
      advocates, as non-alternative surgical treatment in these cases. Wide clinical
      application of oncoplastic surgical techniques gave us possibilities to resolve
      dilemma: excise tumor - containing quadrant with achieving clear margins and
      satisfactory cosmetic outcome, without increasing risk of disease-related
      complications. In cases of multicentricity/ multicocality of breast cancer, total
      axillary lymphadenectomy might be avoided when size of tumor is less than 2 cm
      and there are no signs of malignant involvement of axillary lymph nodes; In case
      of clinically negative axillary lymph nodes - sentinel lymph node biopsy might be
      the standard option. Of course, adjuvant treatment should be planned in
      accordance with the principles of personalized medicine, based on the results of
      multidisciplinary review and taking into consideration modern advanced guidelines
      and recommendations.

PMID- 29227251
TI  - [STEREOTACTIC THALAMOTOMY AND CONTRALATERAL SUBTHALAMOTOMY IN TREATMENT OF
      PARKINSON'S DISEASE].
AB  - Aim - to evaluate the efficacy of combined bilateral stereotactic destruction of
      subcortical nucleus - thalamotomy and contralateral subthalamotomy in patients
      with Parkinson disease. The study included 10 patients with PD, aged 54-73 (mean
      age 61.1+/-5.2 years). The time between two surgeries ranged from 1 to 5 years
      (mean 2.5+/-0.5 years). The surgeries were conducted on CRW Radionics
      stereotactic system using StereoPlan, Atlas (Radionics) andFraimLink (Medtronic)
      software for target calculating. The neuropsychological status was assessed by
      UPDRS II, Hoehn and Yahr scale, Schwab and England scale, MMSE. The postoperative
      follow-up was from 6 months to 5.5 years (mean 3.2+/-0.9 years). After surgeries
      tremor stopped or significantly regressed in 9 (90.0%) patients, muscle tone
      returned to normal in 8 (80.0%) cases and in 7 (70.0%) bradykinesia partially
      regressed. The increase of motor activity was observed in 8 (80.0%) patients.
      Levodopa-induced dyskinesia stopped in 5 (50.0%) patients and motor fluctuations
      regressed in 4 of 5 (80.0%) patients. After the surgery the dose of levodopa
      decreased on average by 36% - from 885+/-245 mg/day to 570+/-165 mg/day. The
      indices of Schwab and England Activities of daily living improved from 56.1% to
      80.7%. The postoperative complications were observed in2 (20.0%) cases. Our
      results demonstrate that bilateral ablative surgery is an effective and safe
      method of treatment of PD. Stereotactic radiofrequency thalamotomy and
      contralateral subthalamotomyimprove overall motor function, increase patient's
      mobility, allow patients to reduce levodopa dose and improve the quality of life.

PMID- 29227249
TI  - Eye opening differentially modulates inhibitory synaptic transmission in the
      developing visual cortex.
AB  - Eye opening, a natural and timed event during animal development, influences
      cortical circuit assembly and maturation; yet, little is known about its precise
      effect on inhibitory synaptic connections. Here, we show that coinciding with eye
      opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from
      somatostatin-expressing interneurons (Sst-INs) to nearby excitatory neurons, but
      not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In
      contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to
      excitatory neurons significantly increases during eye opening. More importantly,
      these developmental changes can be prevented by dark rearing or binocular lid
      suture, and reproduced by the artificial opening of sutured lids.
      Mechanistically, this differential maturation of synaptic transmission is
      accompanied by a significant change in the postsynaptic quantal size. Together,
      our study reveals a differential regulation in GABAergic circuits in the cortex
      driven by eye opening may be crucial for cortical maturation and function.

PMID- 29227252
TI  - [MORTALITY AND MORBIDITY FROM PROSTATE CANCER IN THE REPUBLIC OF KAZAKHSTAN FROM
      2007 TO 2016].
AB  - Worldwide, prostate cancer is the second most common male malignancy after lung
      cancer. However, prostate cancer is less common for the Asian population. We
      performed statistical analysis of official data on newly diagnosed cases of
      prostate cancer based on the annual reports of cancer hospitals in the Republic
      of Kazakhstan for the period of 10 years (2007-2016). We observed an increase in
      the incidence of prostate cancer among the population of Kazakhstan for the
      period of 2007-2016, which may be due to the screening program, which started in
      2013. In the country as a whole, there has been a decrease in mortality over the
      past two years. The peak incidence of prostate cancer falls at the age of 70
      years and older, while at the age of below 40 years this disease is seen only
      sporadically. Since 2009, there has been an increase in the detection of prostate
      cancer in the early (I-II) stages, which is associated with screening tests based
      on evaluation of serum PSA levels.

PMID- 29227253
TI  - [PATHOGENETIC FEATURES OF THE DEVELOPMENT OF OVERACIVE BLADDER IN WOMEN].
AB  - The aim of the research was to study the pathogenetic features of the development
      of the overactive bladder (OAB) in women. 107 women with OAB and a control group
      of 29 healthy women were involved into the study. The hormonal status was studied
      based on the determination of serum concentrations of luteinizing hormone (LH),
      stimulating hormone (FSH), estradiol and progesterone. The urine levels of
      interleukin-1beta (IL-1beta), interleukin-4 (IL-4), interleukin-8 (IL-8), tumor
      necrosis factor alpha (TNF-alpha) and macrophage chemotactic protein-1 (MCP-1)
      were assessed. Decreased level of estradiol was detected in 26.47% of women of
      reproductive age. Elevated urine levels of MCP-1 and IL-8 were found in 35.5% of
      patients. The obtained data testify to the possible pathogenetic role of
      inflammatory changes in the bladder wall, as well as hypoestrogenism in women of
      reproductive age in the development of OAB.

PMID- 29227254
TI  - [MODERN APPROACHES TO DIAGNOSIS AND TREATMENT OF TUMORS OF FEMALE GENITALS OF
      CHILDREN AND ADOLESCENTS (REVIEW)].
AB  - The article discusses the features of epidemiology, morphology, clinical course
      and modern principles of diagnostics and treatment of tumors of female genitals
      of children and adolescents. Special attention is paid to ovarian germ cell
      tumors. The use of immunohistochemical and tumor markers enables the differential
      diagnosis among malignant ovarian germ cell tumors. Nowadays surgical methods,
      chemotherapy and radiation therapy are applied in treatment of tumors of female
      genitals. The main standard of surgical operation of ovarian tumors is removal of
      appendages on the side of the affection. Timely diagnostics and effective
      treatment allow to preserve reproductive function of girls. Foreign publications
      form the basis of the given article, as well as domestic ones. Summarizing of the
      results available from the latest studies in the sphere of features of
      epidemiology, morphology, clinical course and modern principles of diagnostics
      and treatment of tumors of female genitals of children and adolescents.

PMID- 29227255
TI  - [PERSPECTIVE MANAGEMENT IN THE TREATMENT OF GENITAL ENDOMETRIOSIS IN WOMEN WITH
      POLYMORPHISM OF GENS GSTT1 AND GSTM1].
AB  - The article covers the management of patients with internal genital
      endometriosis, in which the polymorphism of the glutathione-S-transferase genes
      has been diagnosed. The aim of our study was to select the optimal conservative
      method for treatment of internal genital endometriosis in women of reproductive
      age by developing complex therapy taking into account the polymorphism of the
      genes of the detoxification system. 102 patients with combined gynecological
      pathology were examined. All patients were subject to a dynamic clinical and
      laboratory examination. According to the presence of GSTT1 genes deletion, GSTM1
      has established research groups and treatment. Analyzing the performed research,
      it was discovered that the clinical efficacy of complex treatment depended on the
      genotypes of patients. The presence of pathologically burdened alleles of genes
      GSTM1 and GSTT1 somewhat reduced the response to standard treatment in the second
      group of patients. However, when comparing the levels achieved in the group I of
      patients, it was determined that in general, the clinical effect of our proposed
      therapy was more pronounced than in the II and III clinical groups. Clinical
      research has proved the effectiveness of hormone therapy combined with
      immunomodulatory and target drug in the form of reducing recurrence and restoring
      fertility.

PMID- 29227256
TI  - [PSYCHOGENIC FACTORS IN THE PATHOGENESIS OF ANTERIOR ISCHEMIC OPTIC NEUROPATHY
      (REVIEW)].
AB  - The purpose of this systematic review is to describe the influence of psychogenic
      factors on the pathogenesis and course of anterior ischemic optic neuropathy
      (AION). Analysis of randomized clinical trials published in the journal indexed
      in PubMed in the period from 1978 to 2016, devoted to the study of the influence
      of various factors on the epidemiology, pathogenesis and course of AION. The
      review of the literature presents basic information on the psychogenic factors
      that affect the course of AION and the areas of clinical application of the data
      under study. Physiological and pathological ways of influence of psychogenic
      factors on regulation of angiogenesis are considered. The main properties of the
      disturbance of retinal microcirculation, the role in the regulation of the
      vascular bed in the norm and under the influence of psychogenic factors in
      patients with AION are described.

PMID- 29227257
TI  - WORLD AND NATIONAL EXPERIENCE IN ORGANIZATION OF PREVENTION OF CARDIOVASCULAR
      DISEASES.
AB  - The aim of the study was to examine the global, European and national experience
      in the implementation of preventive programs and to reveal their value in health,
      economy and social health development. The conducted research has found that the
      implementation of the national program, the correct methodological approach of
      the physician to evaluate risk factors, and implementing preventive measures of
      diseases of the circulatory system bring positive results (reduction of
      prevalence and incidence of cerebral stroke by 13,7% and 1,4%, respectively). The
      results of the analysis of the health care industry pointed out the possible
      directions of optimization of prevention of behavioral risk factors in the
      practice of family medicine as the first point of contact with the patient, where
      preventive measures are essential and effective. Summing up, it should be noted
      that at the level of primary health care, particularly family medicine, with
      effectively coordinated work and correctly set motivation, the preventive
      measures against risk factors of diseases of circulatory system can be quite
      effective.

PMID- 29227258
TI  - [CAUSES OF LETHALITY OF ISCHEMIC STROKE AND WAYS TO IMPROVE PREVENTION METHODS].
AB  - In this article, the authors conduct an in-depth analysis of the causes of
      mortality from ischemic stroke in Almaty city of the Republic of Kazakhstan.
      Based on the materials of the city pathoanatomical bureau for 2015, 2016, and
      nine months of 2017. Autopsy materials and results of histological examination
      were analyzed. The materials of the study were processed using the methods of
      applied biostatistics. According to the results of the study, the authors came to
      the conclusion that the greatest number of patients who died of this pathology is
      in men aged 51 and older than 80 years, and in women 61 and older. When studying
      morphological features, atherothrombotic type AI met in 56% of cases,
      cardioembolic (36%) and hemodynamic type (8%). Taking into account the received
      data, the authors recommend defining the joint responsibility of patients,
      medical workers and the state for violation of the principles of management of
      the causes of the occurrence of ischemic stroke.

PMID- 29227259
TI  - HYPOTHYROIDISM - A SPECIAL COMORBIDITY FACTOR IN PATIENTS WITH OSTEOARTHROSIS:
      CLINICAL, PATHOPHYSIOLOGICAL AND PROGNOSTIC ASPECTS.
AB  - Objective - to study the features of the functional and morphological condition
      of the thyroid gland (TG) in patients with osteoarthrosis (OA), the incidence and
      forms of hypothyroidism and their effects on clinical manifestations, metabolic
      disorders and the results of the treatment of OA and comorbid processes. A
      complex examination involved 312 patients with OA aged 37-76 years. Methods used:
      anthropometric, clinical, ultrasonographic, biochemical, radioimmunological
      (levels of TSH, free thyroxine, antibodies to thyroid peroxidase). It has been
      established that with increasing age in patients OA phenomena are progressing,
      there is an increase in comorbid diseases, especially of the cardiovascular
      system with atherosclerotic genesis, they become more severe. Against this
      background, clinical hypothyroidism was found in 4.44% and subclinical one in
      13.78%. Stratification of the clinical form of hypothyroidism contributed to the
      deterioration of the course and outcome of the treatment of OA and comorbid
      diseases. Both forms of hypothyroidism intensified the degrees of metabolic
      disorders in the blood, reduced the glomerular filtration rate, especially the
      clinical form. Manifestations of hypothyroidism were observed in patients with OA
      with its significant systemic manifestations, high comorbidity rate, in
      individuals aged over 50, especially 60 years, mainly in women (83,72%). In
      patients with OA aged over 50 years with a high comorbidity rate, it is advisable
      to conduct an ultrasound examination of the thyroid gland, to measure the levels
      of TSH, free thyroxine in order to diagnose hypothyroidism early and to treat it
      timely as one of the ways to improve the overall outcomes of the treatment of
      such patients.

PMID- 29227260
TI  - FACTORS ASSOCIATED WITH POST-STROKE FATIGUE DURING THE SECOND HALF YEAR AFTER
      STROKE.
AB  - Post-stroke fatigue (PSF) is a common and often debilitating sequel of both
      ischemic and hemorrhagic strokes Aim - identify socio-demographic, personal and
      psychological factors associated with different PSF domains over the second half
      year after stroke occurrence. There were examined patients consequently in
      definite time points: at 6 months (156 patients), at 9 months (139 patients) and
      at 12 months (128 patients) after ischemic or hemorrhagic strokes. Global PSF and
      certain PSF domains (physical, mental, motivational, activity-related) were
      measured by multidimensional fatigue inventory-20 scale. In univariate logistic
      regression analysis most of the studied variables (gender, marital status,
      education level, apathetic impairments, excessive daytime sleepiness, waist
      circumference, arterial hypertension, ischemic heart disease, atrial
      fibrillation, diabetes mellitus) were not significantly associated with global
      PSF as well as with any PSF aspect at 6, 9 and 12 months after stroke occurrence.
      On the other hand, univariate logistic regression analysis showed reliable
      associations between risk of global PSF, risk of all PSF domains and anxious as
      well as depressive signs, reliable associations between risk of mental PSF and
      cognitive impairments over the second half year after stroke. Multivariate
      logistic regression analysis revealed that depressive signs and cognitive
      impairments were independent predictors of mental PSF over studied post-stroke
      period. Screening and early management of depressive signs, anxious signs and
      cognitive impairments probably may be helpful for PSF prevention over the second
      half year after stroke occurrence.

PMID- 29227261
TI  - CLINICAL FEATURES OF THERAPY OF ANEMIA AND THE SIGNIFICANCE OF ITS FLUCTUATION IN
      THE DEVELOPMENT OF ANEMIA IN DIALYSIS PATIENTS.
AB  - The aim of our study was to examine the features of therapy of anemia, and the
      influence of fluctuation in dose of antianemic drugs on hemoglobin levels in
      dialysis patients. The study included 100 patients with chronic kidney disease
      stage 5D receiving hemodialysis, mean age was 53,4+/-15,8 years. The clinical and
      anamnestic data were studied and laboratory tests were performed in all patients.
      The correlation between hemoglobin level and fluctuations in dose of antianemic
      drugs for 12 months: erythropoietin (R= -0,51, p=0,004) and iron (R= -0,46,
      p=0,01) was determined. The higher doses of erythropoietin and their fluctuation
      and the fluctuation in dose of iron drugs were observed in the group of patients
      with middle degree anemia. The least fluctuation of erythropoietin and iron drugs
      was detected among patients with normal hemoglobin level. There were the
      correlation between the dose of erythropoietin used in the last month with
      transferrin (R=-0,25, p=0.011) and ferritin (R=0,22, p=0.028)and the relationship
      of fluctuations in dose of antianemic drugs and parameters of ferrokinetic, in
      particular, between the fluctuation in dose of iron drugs for 6 months and
      ferritin index (R=0,38, p=0.008), and soluble transferrin receptors (R=-0,37,
      p=0.01). Thus, high variability of doses of antianemic drugs determines less
      successful erythron's response to the treatment in dialysis patients, which
      indicates the need of monitoring the fluctuation of drug's doses.

PMID- 29227262
TI  - [COMBINED COURSE OF BRONCHIAL ASTHMA AND GASTROESOPHAGEAL REFLUX DISEASE: ITS
      CLINICAL, FUNCTIONAL PECULIARITIES, AND MECHANISMS OF ITS CORRECTION].
AB  - The combined course of bronchial asthma (BA) and digestive system pathology is
      one of the most frequent, severe and clinically varied pathology. The purpose of
      the paper - to study the influence of gastroesophageal reflux disease (GERD) on
      the course of BA and the effectiveness of antireflux therapy in combined
      pathology. Patients with combined pathology were treated in full-time department
      more frequently than patients with isolated BA (3,4+/-0,5 per year to - 1,8+/
      0,3; r<0,05). The statistically reliable correlation between frequency of
      heartburn and frequency of cough, which goes over to asthma attacks was observed
      (r=0,59; r<0,05). More severe course of BA was observed in patients with combined
      pathology and was accompanied by reliable decrease in the main functional
      indicators of external breathing (FEB). The antireflux therapy lead to decrease
      in cough intensity and frequency of asthma attacks, especially at night time.
      Also, as a result of antireflux therapy patients were able to refuse to use short
      acting beta2-agonists in 51,7 % and significantly decreased the multiplicity of
      its reception in "on-demand" mode. In patients with GERD more severe course of BA
      was observed. The reliable decrease in the main indicators of FEB, activation of
      inflammatory process (mainly allergic character of inflammation with high level
      of eosinophils in blood and sputum) and increase in level of IL - 4 in the blood.
      The frequency of hospitalization in patients with combined BA and GERD was 2
      times greater than in patients with isolated BA. The complex therapy using
      antireflux has positive effect on clinical symptoms, functional indicators of
      external breathing and markers of inflammation in patients with combined BA and
      GERD.

PMID- 29227263
TI  - [ADAPTIVE REGULATORY MECHANISMS OF ALOPECIA AREATA].
AB  - Failure of adaptive mechanisms leads to structural and functional damage at all
      levels and of neuroendocrinal and immune systems, which are pathogenetic basis of
      development of autoimmune diseases, in particular. The objective of this work was
      to assess the condition of adaptive hormones, such as cortisol and insulin,
      coefficient of stress of adaptive potential "K" and also dermatologic life
      quality index (DLQI) of the diseased with alopecia areata (AA). 48 patients with
      different forms of AA aged between 18 and 52 were examined. Correlation analysis
      identified positive correlation between DLQI and early age of patients, severe
      stage and hair loss for the period of over 12 months (p<0.01). Two types of
      reactions were identified - increase and decrease of content of cortisol and
      insulin in blood depending on the activity, severity stage and length of AA. The
      diseased with signs of progression of the disease, severe stage and duration of
      up to 3 years AA experienced increase of the coefficient "K" (p<0.05) indicates
      increase of tension of adaptive potential of the organism. Decrease of the
      coefficient "K" (p<0.05) during chronisation and duration of the disease of over
      3 years indicates depletion of adaptive mechanisms of organism with possible
      failure of regulatory processes. Identified disorders demonstrate existence of
      maladaptive processes in the diseased with FF and may be considers as potential
      therapeutic targets.

PMID- 29227264
TI  - CHARACTERISTICS OF CHANGES IN COGNITIVE FUNCTIONS OF THE PATIENTS WITH
      HYPERTENSIVE DISEASE.
AB  - Decline of the cognitive functions is one of the modern medicine actual problem.
      The influence of hypertension as modifiable risk factor in the evolution of
      cognitive impairment is emphasized in numerous investigations. Almost all the
      proposed in research literature data were obtained from the investigation of old
      patients group, who had high indexes of blood pressure and stroke histories.
      Therefore, we think that it is very impotent to detect the slight and moderate
      cognitive impairment of hypertensive patients of working age until the expressed
      clinical signs appear. Objective - determine the age and hypertension duration
      influence on the evolution of cognitive impairments in patients with essential
      hypertension of the second stage. There were examined 102 patients with essential
      hypertension of the second stage, which had not any attendant illnesses. Their
      average years were about 49,84+/-0,83 average. Disease duration was approximately
      8,78+/-0,60. According to the purpose of examination all patients were divided by
      age and disease duration into 3 groups. To study cognitive impairment used a
      number of neuropsychological tests. Analyzing the MoCA test data of examined
      patients it should be noted a tendency to decreasing of cognitive function
      indexes with age increasing. Thus, the patients of the first group have no
      cognitive impairment. But authentic lowering of MoCA test results may be noted in
      the patients group of 56 years and higher, up to 6,1% in comparison with the
      patients under 45 years. The indexes of MoCA test in the group of patients with
      arterial hypertension duration more than 10 years were authentically lower
      comparing with the group of patients with disease duration up to 5 years and
      patients with arterial hypertension duration of 5 to 10 years in 9,9% and in 4,9%
      accordantly. We have found that with increasing duration of the disease and age
      the working age patients with essential hypertension of the second stage,
      significant increase in cognitive impairment was observed. Diagnosing of
      cognitive impairment is the measure of prevention of dementia in future and it
      must be an inseparable part of system examination of hypertensive patients.

PMID- 29227265
TI  - [PECULIARITIES OF THE ANALYSIS OF THE LEVEL OF PROINFLAMMATORY CYTOKINS IN THE
      COMMUNITY-ACQUIRED PNEUMONIA IN CHILDREN].
AB  - The high specific gravity in the structure of morbidity in children of all age
      groups, complicated course, determines the urgency of studying the clinical and
      diagnostic aspects of community-acquired pneumonia. In recent years, interest has
      been growing in the study of the child's cytokine status. A number of studies
      indicate that cytokines regulate the severity and duration of the inflammatory
      process. In this regard, the study of the possibility of determining the level of
      proinflammatory cytokines (IL-6 , TNF-alpha) is of great practical importance for
      assessing the prognosis of community-acquired pneumonia in children. In a
      prospective cohort study, 90 children with community-acquired pneumonia aged
      between 5 and 14 years were treated under treatment in the department respiratory
      of the Children>s Hospital in Karaganda, of which 47% were girls (95% CI 31.51% -
      56.33%) and boys 53% (CI 95% 34.91% - 59.88%). The control group included 20
      healthy children. Analysis of the results of the study revealed an increase in
      the content of proinflammatory cytokines in the blood serum and urine on children
      with community-acquired pneumonia depending on the severity of the course. At the
      same time, the equivalence of the cytokine trends in serum and urine determines
      the possibility of noninvasive detection of cytokines, both for characterizing
      the inflammatory response of the organism as such and for predicting the
      development of community-acquired pneumonia, which is especially valuable in
      pediatric practice.

PMID- 29227266
TI  - PREVALENCE OF DISEASES AMONG ADOLESCENT POPULATION IN DNEPROPETROVSK REGION
      (UKRAINE), CORRELATED WITH DRINKING WATER QUALITY DETERIORATION.
AB  - Purpose of research was to study dynamics prevalence of diseases among children'
      population in the separate rural tacsons of Dnepropetrovsk region; to carry out
      correlation analysis between some indicators of drinking water quality and
      prevalence of diseases. Research indicators of prevalence of diseases was carried
      out in the 6 types of tacsons of Dnipropetrovsk region (Ukraine) during 2008 -
      2013 years (totally 522720 indicators). It was proved that (I, II, III, XI, XIII,
      XIV) classes of diseases takes the first place by the prevalence of diseases in
      the majority of rural tacsons. Correlation between higher salt content of the
      potable water taking from decentralized sources and content of some heavy metals
      (Zn, Cu, Mn) and some substances (pH, F, Al, nitrogen ammonia, nitrites,
      nitrates, oxidability) and the prevalence of diseases among children: tumors
      (r=0.87); diseases of blood and hematopoetic organs (r=0.74-0.95); anemia (r=0.79
      0.87); diseases of genitourinary system (r=0.79-0.82); congenital anomalies
      (r=0.87), including circulatory system (r=0.74-0.95) was revealed in the separate
      tacsons of Dnepropetrovsk region (p<0.001).

PMID- 29227267
TI  - [PROBLEMS OF IMMUNIZATION AND SHARED RESPONSIBILITY AT THE LEVEL OF PRIMARY
      HEALTHCARE].
AB  - In this article, the authors consider ways to solve problematic issues related to
      the organization and conduct of immunization among the population in order to
      prevent vaccine-preventable infectious diseases. An in-depth analysis of the
      progress of vaccine prevention has been conducted and the results achieved in the
      world in recent years are reflected. At the same time, the authors identified
      problematic issues related to the successful implementation of further work on
      the prevention of vaccine-preventable infectious diseases. By analyzing the
      reporting data of the medical organization in Almaty and questioning the parents,
      a poorly organized level for ensuring sanitary literacy was revealed, as well as
      beliefs by medical workers about the benefits of vaccination. During the analysis
      of the presented materials, the author managed to highlight the main problems at
      the present stage of the development of immunization.

PMID- 29227268
TI  - CHARACTERISTICS OF WEST SYNDROME IN GEORGIA, PRELIMINARY RESULTS OF THE
      PROSPECTIVE STUDY.
AB  - West syndrome hasn't been thoroughly investigated in Georgia. The purposes of our
      study were a) to assess the clinical and etiological peculiarities of West
      syndrome, based on MRI data and its relation to the long-term outcome; b) to
      assess the evolution of West syndrome and its relation to patient
      characteristics; c) to compare the efficacies of treatments with ACTH and
      antiepileptic drugs (AEDs); d) to evaluate the neuropsychological outcome after
      12 and 24 months and their early predictors. We evaluated 31 patients (17 male,
      14 female) with infantile spasms. Mean age of seizure onset was 6.3 months.
      Inclusion criteria were newly diagnosed patients with infantile spasms from 2 to
      18 months, abnormal EEG and written informed consent of parents/ caregivers. We
      collected birth, family and seizure detailed history. All patients were examined
      neurologically, investigated with prolonged sleep and awake video - EEG, brain
      MRI, developmental screening tests (Ages & Stages Questionnaires(r), Third
      Edition, ASQ-3TM) at the time of admission. Spasm diary was given and filled by
      every parent/caregiver. The video-recording of seizures to study the detailed
      phenomenology of event was done in all cases as well. In 94% of patients (n=29)
      spasm were observed in clusters. EEG investigation revealed hypsarrhythmia in
      majority of cases (n=20; 65%). 19% (n=6) and 16% (n=5) patients had modified
      hypsarrhythmia and other types of EEG changes respectively. In 19 (61%) cases
      neurological examination was normal. 7 patients (22.6%) showed normal
      neuropsychological development. In remaining 12 (38.7%) and 12 (38.7%) cases
      moderate and severe delay of development was revealed accordingly. MRI
      investigation revealed no abnormality in 16% (n=5). 16 (52%) individuals were
      treated with ACTH only. In 12 (39%) cases ACTH and AED were used simultaneously
      and 2 (6.5%) cases were treated with AED only. One year follow-up assessments
      were provided in 22 (74%) cases. One patient died during the study.
      Neuropsychological development was with no changes in 12 (55%) individuals. In 3
      (9.7%) cases some improvement was detected and the deterioration of development
      was identified in 6 (19%) individuals. In all cases with developmental
      deterioration, seizures were started before seven month of age, this association
      was statistically significant (Pearson Chi-Square 6.3; df 1; p=0.019). There was
      no relationship between developmental changes and sex, birth from full term
      pregnancy, infantile spasm type, treatment, or EEG pattern, however. Despite the
      fact, that the number of included patients was small, preliminary findings are in
      accordance to the other published data. The current study is still in process. 12
      24 months follow-up with clinical, EEG and neuropsychological monitoring is
      planned for all cases.

PMID- 29227269
TI  - REYE (RAY'S) SYNDROME: A PROBLEM EVERYONE SHOULD REMEMBER.
AB  - Reye syndrome is a rare but a very dangerous emergency that children and
      teenagers suffer. This threatening condition occurs during the treatment of fever
      in the clinical course of viral diseases with drugs containing acetylsalicylic
      acid and other salicylates. The high mortality rate from this disease is
      associated with the development of a rapidly progressing toxic encephalopathy and
      hepatic insufficiency. The etiology and pathogenesis of the Reye syndrome,
      despite the large number of investigations, is not clear enough. Today, special
      attention is paid to the development of so-called Reye-like syndromes in the
      context of congenital metabolic defects, although cases of the true Reye syndrome
      occur quite often. In spite of the long discussion among scientists, the effect
      of acetylsalicylic acid is an important factor of development of this
      pathological syndrome. Taking this fact into consideration, the use of
      acetylsalicylic acid by children, especially in case of colds, should be strictly
      controlled by a doctor and parents should be informed about possible
      complications, especially the development of the Reye syndrome. This issue is
      very urgent in countries with non-prescription antipyretics realization and a
      high percentage of self-treatment among patients.

PMID- 29227270
TI  - [CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE
      TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].
AB  - The frequency of the combination of congenital heart defects (CHD) and connective
      tissue dysplasia remains poorly understood. And connective tissue dysplasia
      enhance severity the clinical of CHD. The aim of the study was to conduct a
      clinical and laboratory analysis of combinations of congenital heart defects and
      connective tissue dysplasia in children of Semey and to determine the risk for
      the development of these pathologies. The object of the study is the children of
      Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with
      connective tissue dysplasia, healthy children and their mothers. Definition
      complex clinical and laboratory studies in children with CHD and connective
      tissue dysplasia, and their mothers. In children with CHD, the frequency of
      external and visceral signs of dysplasia was high. In 88.1% of cases in children
      with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the
      microelement composition of blood serum and of hemostasis in children with CHD
      were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the
      frequency of signs of dysplasia in mothers over the control group to consider
      dysplasia as a factor that influences the clinical of CHD.

PMID- 29227271
TI  - [IMMUNE SYSTEM INTERNSHIP WITH SYMBIOTIC MICROORGANISMS IN GNOTOBIOTIC ANIMAL'S
      INTESTINUM ILEUM].
AB  - Structures, responsible for acceptive (comensaling relation) and protective
      (pathogenic defense) immunity, were studied and compared in small intestine - to
      ileum mucosa. Data shown, that main application of the both domains of immune
      system is to support the correlation between body and foreign microbes, but they
      response is different. Most significant differences are as follows: in acceptive
      reactions presented only in aseptic animals - gnotobionts, inflammatory changes
      absent, so immune reaction complex develops into physiological condition.
      Symbiotic reactions release in mucosa epithelial cells, also in cells,
      responsible for adaptive and congenital immune reactivity. Thus, acceptive immune
      reactions contribute symbiotic biocenosis versus elimination; which is function
      of protective immunity.

PMID- 29227272
TI  - [STUDY OF SOME PLANT SEED LIPIDS GROWING IN GEORGIA].
AB  - The purpose of the research was to study seed lipids of cultivated plants:
      Medicago sativa, Ruta graveolens L., Linum usitatissimum L., which are growing on
      experimental field of I. Kutateladze Institute of Pharmacochemistry. From the
      above-mentioned plant seeds was obtained the sum of neutral and polar lipids, the
      classes were determined qualitatively. Using standard methods were determined
      some physico-chemical constant of oils. Fatty acids was established qualitatively
      and was determined quantitatively using Gas chromatography and High performance
      liquid chromatography methods. As a result of research in the seed oil of
      Medicago Sativa was revealed high percentage content of Oktadekadien - 9,12 fatty
      acid. Oktadekadien -9 dominates in the oil obtained from the seeds of Ruta
      graveolens L. and Oktadekantrien - 9,12,15 dominates in the oil obtained from the
      seeds of Linum usitatissimum L. Phospholipids were established qualitatively and
      using spectrophotometric method were determined In the sum of polar lipids:
      (lambda 820 nm). The oils which are obtained from above-mentioned plant seeds
      contains biologically active compounds, which gives the opportunity to use these
      oils as in medical practice, also in cosmetology.

PMID- 29227273
TI  - [POISONING BY PSYCHOPHARMACOLOGICAL DRUGS IN AZERBAIJAN: THE RESULTS OF 8-YEAR
      PROSPECTIVE OBSERVATION].
AB  - Acute poisoning of chemical etiology is a significant global public health
      problem. The aim of this study was the analysis of the toxicoepidemiological
      structure of psychopharmacological drugs poisoning in Azerbaijan. We collected
      and analyzed the data on all cases of acute poisoning by psychopharmacological
      drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the
      Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. The total number
      of patients with acute intoxication by psychopharmacological drugs was 3,413,
      which was 48.3% of all cases of poisoning by drugs, medicaments and biological
      substances (T36-T50). The predominance of women was registered in all age groups.
      1114 patients or 32.6% were in 15-24 years old age group. The highest percentage
      of poisonings at category T42 of ICD-10 were benzodiazepine-type drugs (35.8%),
      and at category T43 - antipsychotic and neuroleptic drugs (19.2%). In the
      structure of benzodiazepine poisoning, the first and second ranked places
      belonged to phenazepam (71.0%) and clonazepam - 16.6%. In addition, another 120
      cases (5.5%) of poisonings in the T42 cohort were caused by "Z drugs", which have
      similar therapeutic effect to benzodiazepines (zolpidem and zopiclone). Among the
      antipsychotic and neuroleptic poisonings, thioridazine, trifluoperazine,
      levomepromazine, chlorpromazine, and periciazine accounted for 91% of all cases
      of intoxication in this cohort. Barbiturates, in view of their toxicity and
      narrow range of therapeutic dosages, now lost their importance as antiepileptic
      and hypnotic drugs. Only 4.9% of all cases of poisoning, classified under
      category T42, was due to the use of barbiturates (mainly phenobarbital).
      Poisonings with iminostilbenes were presented by carbamazepine poisoning only.
      Most patients in this cohort received this anticonvulsant drug as prescribed by a
      doctor. Acute intoxications by tricyclic antidepressants in 91.5% were presented
      by cases of amitriptyline poisoning. Intoxication by serotonin reuptake
      inhibitors antidepressants, were relatively rare (3.8% of all cases of poisoning
      in T43). Among the poisonings with butyrophenone and thioxanthene neuroleptics,
      the first ranked place was occupied by cases of haloperidol poisoning, which
      accounted for 82.6% in this cohort. In the group of intoxications with other
      antipsychotic and neuroleptic drugs, the first ranked place belonged to the
      poisoning with clozapine - a total of 83 cases or 47.2% in cohort. Poisonings by
      psychopharmacological drugs occupy the first ranking place among poisoning by
      drugs, medicaments and biological substances (T36-T50). Increased control over
      the prescription and sale of psychopharmacological drugs, a reduction the number
      of tablets in one package, as well as increased attention to vulnerable groups of
      the population could be help to reduce the percentage of these poisonings in
      Azerbaijan.

PMID- 29227274
TI  - STUDY OF PHARMACOMETRIC INDEXES OF DOSING REGIMEN OF ANTIHYPOXANT OKAGERM-4.
AB  - In series of pharmacometrics research by determination of an optimum model of
      dosing is established that introduction of OKAGERM-4 in a dose of 96.8 mg/kg
      administered 40 minutes before the start of hypoxic damage realizes in maximum
      increase of estimated life expectancy of animals in hermetically sealed
      containers (65.57 min), ensuring a maximum effect of potential
      pharmacotherapeutic remedy - tartaric acid-based coordination compound of
      germanium with manganese. Thus, the results of pharmacometric research aimed to
      develop dosing regimen of OKAGERM-4 may be the base for future episodes of its
      pre-clinical study.

PMID- 29227275
TI  - ANTIOXIDANT, ANTI-INFLAMMATORY ACTIVITY OF GEORGIAN LEGUMINOUS CROPS CULTURES.
AB  - The aim of the study was to identify the common in Georgia leguminous crops
      culture with pronounced antioxidant, anti-inflammatory activity. The primary
      evaluation of the antiinflammatory effects of beans was performed on the
      experimental models of MDCK and Jurkat cells model systems. Extracts of various
      varieties of legumes (Beans "Kidney", Meadow beans, Beans Shulavera, Batumian
      beans, Beans "Udelebi", green peas, peas Shulavera, lentils Lens Culinaris, Soy)
      were added to the intact or incubated under oxidative stress conditions Jurkat
      and MDCK cells. Cells' vitality was determined by MTT test. On the basis of
      analysis of the obtained results, we concluded that: - Meadow beans extract (low
      doses) revealed cytoprotective effect on the intact and incubated under oxidative
      stress conditions immune (Jurkat) and epithelial (MDCK) cells. High antioxidant,
      cytoprotective activity of this extract correlates with high polyphenols content
      in it. - The extract of Shulavera beans did affect the intact Jurkat and MDCK
      cells, but showed pronounced cytoprotective activity on these cells incubated
      under the oxidative stress conditions. High antioxidant, cytoprotective activity
      of this extract correlates with high content of polyphenols in it. - Low dose of
      lentils Lens Culinaris extracts revealed cytoprotective activity on the incubated
      under oxidative stress conditions MDCK cells, but was inactive in case of intact
      MDCK and incubated in different conditions immune Jurkat cells. The selective
      antioxidant activity of this extract is related with its other constituent
      components, but not polyphenols. - Despite high polyphenols content and high
      antioxidant activity in vivo, Batumian beans revealed moderate cytoprotective
      activity on intact and incubated under oxidative stress conditions Jurkat cells,
      suppressive activity on the intact MDCK cells and was inactive in relation to the
      incubated under oxidative stress conditions MDCK cells. Based on these findings,
      we can identify extracts with selective protective, anti-inflammatory (Meadow
      beans, Shulavera beans extracts), cytoprotective (lentil Lens Culinaris extract)
      and immunomodulatory (Butumian bean extract) properties. Further studies are
      needed to identify and verify the mechanisms of activity of these Extracts in
      order to develop effective selective dietary supplements.

PMID- 29227276
TI  - ALTERATION IN THE CYTOKINE SECRETION PATTERN IN T CELLS OF PATIENTS WITH CYSTIC
      FIBROSIS CAUSED BY DNA METHYLTRANSFERASE INHIBITOR 5-AZACITIDINE.
AB  - Cystic fibrosis (CF) is the autosomal-recessive disorder caused by mutation in
      the cystic fibrosis transmembrane conductance regulator gene (CFTR). The Airway
      inflammation plays a central role in the progression of CF disease. Cystic
      fibrosis characterized by the overproduction of the pro-inflammatory cytokines
      and reduced expression of anti-inflammatory cytokines. Although the mechanisms of
      abnormal cytokine expression is still poorly understood, altered epigenetic
      regulations in T cells might contribute. In the present study we examined the
      expression of IFN-gamma and IL-10 by CF T cells prior to and following 5-azaC
      treatment. In addition we investigated DNMTs levels in nuclear extracts of CD4+ T
      cells derived from CF and non-CF individuals. Seven CF patients (age: 5-12 years)
      were included in the study and compared to six age-matched healthy subjects (age:
      6- 13 years). CD4+ T cells were isolated from PBMC using CD4 MicroBead kit
      (Miltenyi Biotec GmbH) and were cultured in RPMI 1640 medium at 37 degrees C with
      5% CO2, in presence or absence of 5-azacytidine. Concentrations of IL-10 and
      gamma-INF in CD4+ T Cells were measured by ELISA (eBoiscience, san Diego, CA,
      USA). In our study we showed that 5 Azacytidine alters nuclear levels of DNMT 3a
      as well as modulates cytokine levels in CD4+ T cells derived from CF patients.
      After 5-azaC treatment secretion of IFN-gamma was significantly decreased in CF T
      cells, while amount of IL-10 was elevated by ~2.5 times compared to untreated
      controls (P<0.05). In summary, data presented in this report demonstrates that
      epigenetic mechanisms such as DNA methylation may be considered as a one of the
      potential therapeutic target in a treatment of Cystic Fibrosis.

PMID- 29227277
TI  - USE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE IN GEORGIA.
AB  - In Georgia, like in most countries globally, people commonly resort to
      complementary and alternative medicine (CAM). However, not much is known about
      CAM practices there. The aim of the study was to document common practices of CAM
      in Georgia and related patient attitudes. We collected data from peoples who
      commonly use CAM at 20 service provision centers in Georgia using cluster
      sampling from 300 patients. We admininstered a cross-sectional survey and
      conducted descriptive statistical analyses. People in Georgia use CAM either for
      prevention to improve general health (33%) or to treat chronic conditions (36%),
      spending about 25 Euros per month out of pocket. Most (77%) get their knowledge
      about CAM from family or friends , less than half (44%) from books or media, and
      11% from medical providers. A close person's advice or experience was the most
      common rationale given for CAM use (54%). In our sample, 17% either don't trust
      or are unsatisfied with conventional medicine, 29% found CAM treatment "very
      effective" and 61% "quite/partially" effective; only 5% not effective.
      Conventional treatment was stopped in half of the cases. 35% of respondents
      informed their physicians of their CAM use, while about half did not. Public
      mistrust towards conventional medicine, CAM user high satisfaction, relatively
      low cost of such services in Georgia - are the factors letting us to suggest that
      CAM use will further increase. Frequent self taking decisions made by patients to
      stop physician prescribed treatment, not informing physicians on CAM use, as well
      as other factors put patients health at risk. Further research and capacity
      building in practice, education and other related aspects are needed to establish
      evidence-based regulation and standards for CAM in Georgia that ensure informed
      decision making and patient safety.

PMID- 29227278
TI  - An automated method for dynamic red blood cell aggregate detection in
      microfluidic flow.
AB  - OBJECTIVE: Red blood cell (RBC) aggregation is a unique phenomenon that occurs
      when red blood cells are subjected to low shear rates. Little is known about the
      sizes, shapes and behaviour of aggregates flowing in healthy humans. However,
      excessive aggregation has been shown to be an indication of pathological
      conditions. Therefore, characterizing RBC aggregates is important to medical
      research. The objective of this study was to develop a reliable technique based
      on image processing to assess and characterize human RBC aggregation subjected to
      controlled and measurable shear rates in a two-fluid flow microfluidic shearing
      system. APPROACH: Images of RBC suspensions at [Formula: see text], [Formula: see
      text] and [Formula: see text] entrained by a phosphate buffered saline solution
      in a PDMS microchannel were captured with a high speed camera. An algorithm for
      processing the RBC aggregate images is presented and validated (1) on a sample of
      known diameter hollow glass microspheres and (2) by comparing RBC aggregate size
      results with those of an ImageJ image processing technique and those obtained by
      manual detection by two independent researchers. MAIN RESULTS: The proposed image
      processing algorithm provides a very good agreement with the manufacturer data
      for the glass microspheres. It also performs well on the RBC suspension images,
      with errors of 2-4 [Formula: see text] with respect to the manual results.
      SIGNIFICANCE: The proposed automated method for RBC aggregate detection is found
      to be reliable and fairly accurate and will serve researchers and, perhaps in the
      future, clinicians to assess healthy and pathological RBC aggregation under
      flowing conditions.

PMID- 29227279
TI  - Drug-eluting balloon: design, technology and clinical aspects.
AB  - A drug-eluting balloon is a non-stent technology in which the effective
      homogenous delivery of anti-proliferative drugs is processed by the vessel wall
      through an inflated balloon. This is done to restore luminal vascularity in order
      to treat atherosclerosis, in-stent restenosis and reduce the risk of late
      thrombosis without implanting a permanent foreign object. The balloon technology
      relies on the concept of targeted drug delivery, which helps in the rapid healing
      of the vessel wall and prevents the proliferation of smooth muscle cells. Several
      drug eluting devices in the form of coated balloons are currently in clinical
      use, namely DIOR(r), PACCOCATH(r), SeQuent(r)Please and IN.PACTTM. The device
      varies in terms of the material used for making the balloon, the coating
      techniques, the choice of coated drug and the release pattern of the drug at the
      site. This review gives an insight into the evolution, rationale and comparison
      of the marketed drug-eluting balloons. Here, different coating techniques have
      been analysed for the application and critical analysis of available DEB
      technologies, and a technical comparison has been done.

PMID- 29227280
TI  - Proapoptotic PUMA targets stem-like breast cancer cells to suppress metastasis.
AB  - Breast cancer cells with stem cell properties are key contributors to metastatic
      disease, and there remains a need to better understand and target these cells in
      human cancers. Here, we identified rare stem-like cells in patients' tumors
      characterized by low levels of the proapoptotic molecule p53-upregulated
      modulator of apoptosis (PUMA) and showed that these cells play a critical role in
      tumor progression that is independent of clinical subtype. A signaling axis
      consisting of the integrin alphavbeta3, Src kinase, and the transcription factor
      Slug suppresses PUMA in these cells, promoting tumor stemness. We showed that
      genetic or pharmacological disruption of alphavbeta3/Src signaling drives PUMA
      expression, specifically depleting these stem-like tumor cells; increases their
      sensitivity to apoptosis; and reduces pulmonary metastasis, with no effect on
      primary tumor growth. Taken together, these findings point to PUMA as a key
      vulnerability of stem-like cells and suggest that pharmacological upregulation of
      PUMA via Src inhibition may represent a strategy to selectively target these
      cells in a wide spectrum of aggressive breast cancers.

PMID- 29227281
TI  - Targeting Mcl-1 enhances DNA replication stress sensitivity to cancer therapy.
AB  - DNA double-strand breaks (DSBs) are mainly repaired either by homologous
      recombination (HR) or by nonhomologous end-joining (NHEJ) pathways. Here, we
      showed that myeloid cell leukemia sequence 1 (Mcl-1) acts as a functional switch
      in selecting between HR and NHEJ pathways. Mcl-1 was cell cycle-regulated during
      HR, with its expression peaking in S/G2 phase. While endogenous Mcl-1 depletion
      reduced HR and enhanced NHEJ, Mcl-1 overexpression resulted in a net increase in
      HR over NHEJ. Mcl-1 directly interacted with the dimeric Ku protein complex via
      its Bcl-2 homology 1 and 3 (BH1 and BH3) domains, which are required for Mcl-1 to
      inhibit Ku-mediated NHEJ. Mcl-1 also promoted DNA resection mediated by the Mre11
      complex and HR-dependent DSB repair. Using the Mcl-1 BH1 domain as a docking
      site, we identified a small molecule, MI-223, that directly bound to BH1 and
      blocked Mcl-1-stimulated HR DNA repair, leading to sensitization of cancer cells
      to hydroxyurea- or olaparib-induced DNA replication stress. Combined treatment
      with MI-223 and hydroxyurea or olaparib exhibited a strong synergy against lung
      cancer in vivo. This mechanism-driven combination of agents provides a highly
      attractive therapeutic strategy to improve lung cancer outcomes.

PMID- 29227282
TI  - Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in
      acute myeloid leukemia.
AB  - Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of
      acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication
      (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial
      therapeutic efficacy, resistance rapidly develops through mechanisms that are
      incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic
      cells and found that upregulation of the Tec family kinase BMX occurs during
      sorafenib resistance. This upregulation was recapitulated in an in vivo murine
      FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance. Mechanistically, the
      antiangiogenic effects of sorafenib led to increased bone marrow hypoxia, which
      contributed to HIF-dependent BMX upregulation. In in vitro experiments, hypoxia
      dependent BMX upregulation was observed in both AML and non-AML cell lines.
      Functional studies in human FLT3-ITD+ cell lines showed that BMX is part of a
      compensatory signaling mechanism that promotes AML cell survival during FLT3
      inhibition. Taken together, our results demonstrate that hypoxia-dependent
      upregulation of BMX contributes to therapeutic resistance through a compensatory
      prosurvival signaling mechanism. These results also reveal the role of off-target
      drug effects on tumor microenvironment and development of acquired drug
      resistance. We propose that the bone marrow niche can be altered by anticancer
      therapeutics, resulting in drug resistance through cell-nonautonomous
      microenvironment-dependent effects.

PMID- 29227283
TI  - SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls
      melanoma growth.
AB  - SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC),
      plays important roles in NF-kappaB signaling and inflammation. Here, we have
      demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth.
      We observed that SHARPIN interacted with PRMT5, a type II protein arginine
      methyltransferase, and increased its multiprotein complex and methyltransferase
      activity. Activated PRMT5 controlled the expression of the transcription factors
      SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the
      transcriptional corepressor SKI. Activation of PRMT5 by SHARPIN counteracted
      PRMT5 inhibition by methylthioadenosine, a substrate of methylthioadenosine
      phosphorylase, which is codeleted with cyclin-dependent kinase inhibitor 2A
      (CDKN2A) in approximately 15% of human cancers. Collectively, we identified a
      LUBAC-independent role for SHARPIN in enhancing PRMT5 activity that contributes
      to melanomagenesis through the SKI/SOX10 regulatory axis.

PMID- 29227284
TI  - Cografting astrocytes improves cell therapeutic outcomes in a Parkinson's disease
      model.
AB  - Transplantation of neural progenitor cells (NPCs) is a potential therapy for
      treating neurodegenerative disorders, but this approach has faced many challenges
      and limited success, primarily because of inhospitable host brain environments
      that interfere with enriched neuron engraftment and function. Astrocytes play
      neurotrophic roles in the developing and adult brain, making them potential
      candidates for helping with modification of hostile brain environments. In this
      study, we examined whether astrocytic function could be utilized to overcome the
      current limitations of cell-based therapies in a murine model of Parkinson's
      disease (PD) that is characterized by dopamine (DA) neuron degeneration in the
      midbrain. We show here that cografting astrocytes, especially those derived from
      the midbrain, remarkably enhanced NPC-based cell therapeutic outcomes along with
      robust DA neuron engraftment in PD rats for at least 6 months after
      transplantation. We further show that engineering of donor astrocytes with Nurr1
      and Foxa2, transcription factors that were recently reported to polarize harmful
      immunogenic glia into the neuroprotective form, further promoted the neurotrophic
      actions of grafted astrocytes in the cell therapeutic approach. Collectively,
      these findings suggest that cografting astrocytes could be a potential strategy
      for successful cell therapeutic outcomes in neurodegenerative disorders.

PMID- 29227285
TI  - Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease.
AB  - Histone protein modifications control fate determination during normal
      development and dedifferentiation during disease. Here, we set out to determine
      the extent to which dynamic changes to histones affect the differentiated
      phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we
      examined the consequences of shifting the balance of the repressive histone H3
      lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity
      and subtotal nephrectomy (SNx) studies indicated that deletion of the histone
      methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized
      mice to glomerular disease. H3K27me3 was enriched at the promoter region of the
      Notch ligand Jag1 in podocytes, and derepression of Jag1 by EZH2 inhibition or
      knockdown facilitated podocyte dedifferentiation. Conversely, inhibition of the
      Jumonji C domain-containing demethylases Jmjd3 and UTX increased the H3K27me3
      content of podocytes and attenuated glomerular disease in adriamycin
      nephrotoxicity, SNx, and diabetes. Podocytes in glomeruli from humans with focal
      segmental glomerulosclerosis or diabetic nephropathy exhibited diminished
      H3K27me3 and heightened UTX content. Analogous to human disease, inhibition of
      Jmjd3 and UTX abated nephropathy progression in mice with established glomerular
      injury and reduced H3K27me3 levels. Together, these findings indicate that
      ostensibly stable chromatin modifications can be dynamically regulated in
      quiescent cells and that epigenetic reprogramming can improve outcomes in
      glomerular disease by repressing the reactivation of developmental pathways.

PMID- 29227287
TI  - Creating a graft-friendly environment for stem cells in diseased brains.
AB  - Most of the adult CNS lacks regenerative activity in terms of both neuron birth
      and neurite outgrowth. While this regeneration-unfriendly environment of the
      adult CNS may preserve the existing neuronal circuitry that takes years to
      develop in higher organisms, it also poses a major obstacle for CNS repair later
      in life. In this issue of the JCI, Song et al. report on their development of a
      strategy that uses region-specific and molecularly engineered astrocytes to turn
      an unfavorable brain environment into a favorable one for engrafted neural
      stem/progenitor cells (NSC/NPCs). In a rat model of Parkinson's disease (PD),
      cografting NPCs with midbrain-derived astrocytes engineered to overexpress the
      transcription factors Nurr1 and Foxa2 promotes maturation and survival of the
      graft, resulting in therapeutic improvement. The results of this study raise the
      prospect of using modified astrocytes to improve the survival, maturation, and
      integration of engrafted NSC/NPCs as a restorative treatment for PD.

PMID- 29227288
TI  - Physician and Nurse Perceptions of Gentle Cesarean Birth.
AB  - BACKGROUND: Protocols for neonatal care and mother-baby interaction at cesarean
      birth frequently differ from those at vaginal birth. There is increasing interest
      in adopting family-friendly or gentle protocols for women having cesarean birth.
      Current evidence suggests challenges in achieving interdepartmental cooperation
      and consensus are potential barriers to implementing gentle cesarean protocols.
      PURPOSE: To describe how care providers' professional role and characteristics
      may affect perception about gentle cesarean birth techniques and inform specific
      concerns about protocol changes. STUDY DESIGN AND METHODS: A cross-sectional
      survey with mixed-methods analysis incorporating quantitative and qualitative
      conventional content analysis was used. A structured survey was distributed via
      email to all care providers on the labor and birth unit, including attending
      physicians, resident physicians in training, fellows, labor nurses, respiratory
      therapists, and operating room technicians. Quantitative responses were analyzed
      with bivariable tests and logistic regression to describe associations between
      provider attitudes and provider characteristics. Open-ended responses were
      analyzed with conventional content analysis to develop a model describing
      influences on overall provider attitudes. RESULTS: Physicians and nurses
      generally have positive attitudes on benefits of gentle cesarean techniques.
      Their perceptions overall are informed by the balance of concerns about patient
      safety and logistical challenges versus perceived benefits of the techniques. On
      an individual level, care provider demographic and professional characteristics
      of gender and prior experience affected attitudes more than their specific role
      in patient care. CLINICAL IMPLICATIONS: Most labor and birth care providers have
      positive attitudes about gentle cesarean birth. Implementation of such programs
      should prioritize patient safety, educate physician and nurses about potential
      benefits for patients, and use experienced physicians and nurses as ambassadors
      to increase acceptance.

PMID- 29227289
TI  - Perioperative steroid therapy: where's the evidence?
AB  - PURPOSE OF REVIEW: Review of historical and current evidence of adrenal
      suppression in patients on chronic glucocorticoid therapy during perioperative
      period, and discussion of current recommendations for perioperative stress dose
      steroid administration. RECENT FINDINGS: Evidence suggests low incidence of
      perioperative adrenal insufficiency in patients receiving chronic glucocorticoid
      therapy. Recent studies show no difference in survival or hemodynamic sequella by
      withholding perioperative stress steroids; however, these studies are limited in
      size and universal applicability. SUMMARY: Current recommendations for
      perioperative stress dose steroids for patients on chronic glucocorticoid therapy
      are based on duration and dose of maintenance steroids. All patients should take
      their regular daily dose of steroid preoperatively regardless of dose or
      chronicity of prior treatment. Additional, stress dose steroid dosing is based on
      patient risk of adrenal suppression and surgical complexity and stress.

PMID- 29227290
TI  - Postoperative thrombocytopenia: why you should consider antiplatelet therapy?
AB  - PURPOSE OF REVIEW: This review addresses the role of platelets in perioperative
      ischemic complications involving the brain, kidneys, and gastrointestinal tract,
      and long-term survival in patients undergoing coronary artery bypass grafting
      surgery. Importantly, findings of several recent clinical studies will be
      discussed with emphasis on platelet activation and leukocyte inflammatory
      responses as important mediators of vascular microthrombosis and ischemic injury.
      RECENT FINDINGS: Our recent findings suggest that in some patients, the
      hemostatic balance during and after surgery may shift toward a hypercoagulable
      state and contribute to acute organ failure. SUMMARY: For over 6 decades, major
      postoperative complications after cardiac surgery have remained unchanged. The
      potential influence of microthrombosis involving platelets has been
      underappreciated and use of perioperative antiplatelet therapy remains very
      limited - primarily because of a culture of fear of bleeding.

PMID- 29227291
TI  - Three-Factor Versus Four-Factor Prothrombin Complex Concentrate for Warfarin
      Reversal-A Critical Appraisal of the Evidence.

PMID- 29227286
TI  - Drug-perturbation-based stratification of blood cancer.
AB  - As new generations of targeted therapies emerge and tumor genome sequencing
      discovers increasingly comprehensive mutation repertoires, the functional
      relationships of mutations to tumor phenotypes remain largely unknown. Here, we
      measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome,
      transcriptome, and DNA methylome analysis to understand determinants of drug
      response. We assembled a primary blood cancer cell encyclopedia data set that
      revealed disease-specific sensitivities for each cancer. Within chronic
      lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or
      more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an
      important driver of CLL. Based on drug responses, the disease could be organized
      into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR,
      or MEK signaling and associated with mutations, gene expression, and DNA
      methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non-BCR
      dependent manner. Multivariate modeling revealed immunoglobulin heavy chain
      variable gene (IGHV) mutation status and trisomy 12 as the most important
      modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were
      associated with outcome. This study overcomes the perception that most mutations
      do not influence drug response of cancer, and points to an updated approach to
      understanding tumor biology, with implications for biomarker discovery and cancer
      care.

PMID- 29227292
TI  - Association of hyperglycemia, systolic and diastolic hypertension, and
      hyperthermia relative to baseline in the acute phase of stroke with poor outcome
      after intravenous thrombolysis.
AB  - : In the acute phase of ischemic stroke, the trend of some physiological
      variables, such as blood glucose (BG), blood pressure, and body temperature (BT),
      might influence outcome. We aimed to assess the association of hyperglycemia,
      systolic and diastolic hypertension, and hyperthermia relative to baseline BG,
      systolic blood pressure, diastolic blood pressure and BT, respectively, in the
      first 12 h with poor outcome after intravenous thrombolysis (IVT). We conducted a
      retrospective analysis of data prospectively collected from 200 consecutive
      anterior ischemic stroke patients treated with IVT. Outcome measures were no
      neurological improvement at 24 h (National Institutes of Health Stroke Scale
      (NIHSS) score at 24 h >=NIHSS score at baseline), and unfavorable functional
      outcome [modified Rankin Scale (mRS) score 3-6] at 3 months. No neurological
      improvement at 24 h was noted in 52 (26%) patients and mRS 3-6 at 3 months in 68
      (34%) patients. The multivariate analyses showed that odds ratios (ORs) for no
      neurological improvement at 24 h were higher in patients with hyperglycemia
      relative to baseline [OR 3.50, 95% confidence interval (CI) 1.43-8.57, P =
      0.006], and hyperthermia relative to baseline (OR 2.88, 95% CI 1.20-6.91, P =
      0.018). OR for 3-month mRS score 3-6 was higher in patients with hyperthermia
      relative to baseline (OR 3.05, 95% CI 1.20-7.74, P = 0.019). Hyperglycemia and
      hyperthermia relative to baseline in the first 12 h after IVT are associated with
      no neurological improvement at 24 h. Hyperthermia relative to baseline is also
      associated with unfavorable functional outcome at 3 months.

PMID- 29227293
TI  - An ex-vivo model of shear-rate-based activation of blood coagulation.
AB  - : The study presents a model of shear-stress-based platelet activation. Twenty
      eight patients (22 free from anticoagulants and major antiplatelet agents, and
      six under the effects of P2Y12 platelet inhibitors) participated. The main
      purpose was to verify the hypothesis that a model of shear-dependent blood
      activation does not require artificial activators to trigger clot formation.
      Whole blood collected from the patients received platelet function tests [ADPtest
      and thrombin receptor-activating peptide (TRAP)test] and was tested with a cone
      on-plate viscosimeter at a shear rate of 100 s. Changes in blood viscosity were
      characterized by a time-to-gel point (TGP), a maximum clot viscosity and a steady
      clot viscosity (SCV). In patients free from major antiplatelet effects, the TGP
      was 180 s (interquartile range 148-290 s), while in patients under double
      antiplatelet therapy the TGP was significantly (P = 0.039) longer (345 s,
      interquartile range 250-452 s). The SCV was 16 centipoise (cP) (interquartile
      range 11-47 cP) in the patients free from major antiplatelet agents,
      significantly (P = 0.012) higher than in patients under double antiplatelet
      therapy (10 cP, interquartile range 6-11 cP). There was a significant (P = 0.011)
      association between platelet function at the TRAPtest and the maximum clot
      viscosity, and between TRAPtest and the SCV (P = 0.021). A shear rate of 100 s
      triggers clot formation through a primary role of platelet activation in this
      model of blood activation.

PMID- 29227294
TI  - Immediate and 24-h blood pressure-lowering effects of arm crank exercise in
      patients with traumatic lower-limb amputation: a randomized cross-over study.
AB  - AIM: This study aimed to investigate the clinic and 24-h postexercise hypotension
      (PEH) after a moderate-intensity arm crank exercise session in individuals with
      traumatic lower-limb amputation. PARTICIPANTS AND METHODS: Nine men (46+/-17
      years) with unilateral traumatic lower-limb amputation participated in two
      experimental sessions conducted randomly: an aerobic exercise (EXE: arm crank
      ergometer, 30 min) or a control session (CON: participants remained seated on the
      cycle ergometer, 30 min). Clinic and 24-h systolic, diastolic, and mean blood
      pressure (BP) response were measured after both sessions. The clinical
      measurements of blood flow and forearm vascular resistance (FVR) were also
      performed. RESULTS: Compared with the preintervention period, the BP levels did
      not change in the CON session. However, EXE resulted in a significant hypotensive
      effect in systolic (-10+/-0.9 mmHg, P<=0.05), diastolic (-11+/-1.5 mmHg,
      P<=0.05), and mean BP (-11+/-1.2 mmHg, P<=0.05) during the entire postexercise
      period. The PEH was accompanied by a decreased FVR over the entire
      postintervention period (P<=0.05). Significant reductions were found for 24-h
      average systolic, diastolic, and mean BP levels (P=0.03, 0.01, and 0.02,
      respectively) following EXE compared with the CON session. CONCLUSION: These
      results showed, for the first time, that individuals with traumatic lower-limb
      amputation presented immediate and 24-h PEH after a single bout of arm crank
      exercise testing. The PEH at the clinic condition was justified, at least in
      part, by the reduction in peripheral FVR.

PMID- 29227295
TI  - An Unusual Presentation of Pituitary Gland Apoplexy With Noninfectious
      Meningitis.
AB  - Pituitary adenomas make up 10% of intracranial tumors, but because of their
      location, they may go undetected for long periods. In this article, we report the
      case of a 68-year-old white man found deceased in his residence, who died of
      acute pituitary tumor apoplexy. He was known to have severe symptoms including
      acute headache, vision loss, and altered behavior. When found, his home was in
      extreme disarray, mimicking a possible assault. At autopsy, the decedent had
      multiple superficial abrasions about the upper and lower extremities, as well as
      a 2.5 * 3-cm pituitary adenoma compressing the carotid arteries and optic nerves.
      Initial coroner and police investigators were strongly considering homicide with
      robbery as a motive, given the disarray present at the scene. This case
      highlights the importance of postmortem examination of the pituitary gland in all
      cases where neurological symptoms are reported prior to death.

PMID- 29227296
TI  - Lesch-Nyhan syndrome and its variants: examining the behavioral and
      neurocognitive phenotype.
AB  - PURPOSE OF REVIEW: Lesch-Nyhan Syndrome (LNS) is a metabolic disorder involving
      mutations in the HGPRT1 gene that result in hyperuricemia, intellectual
      disability, a dystonic movement disorder, and compulsive self-injury with self
      mutilation. The aim of this review is to summarize recent research that documents
      the extended behavioral, neurologic, and neurocognitive phenotype in classic LNS,
      to describe milder variants of HGprt deficiency that do not self-injure and have
      less severe neurological and cognitive deficits, and to provide an update on
      treatment for associated psychiatric and behavioral disorders. RECENT FINDINGS:
      Psychiatric management utilizes combined behavioral and pharmacological treatment
      in conjunction with protective equipment and dental management to avert self
      injury. Pharmacological management focuses on stabilization of mood and anxiety
      management. S-adenosylmethionine (SAMe), a physiological intermediate in
      methylation and transsulfuration, has shown beneficial effects in carefully
      selected patients who can tolerate the drug. Deep brain stimulation is shown in
      several case reports and series to reduce or eliminate self-injury and
      aggression, and in some cases, modify dystonia. SUMMARY: This review highlights
      progress in our understanding of the behavioral and neurocognitive phenotype of
      Lesch-Nyhan syndrome (HGprt deficiency) and its variants, describes psychiatric
      and behavioral management, and discusses prospects for new therapies.

PMID- 29227297
TI  - Neuropsychiatric effects of epilepsy in developmental disorders.
AB  - PURPOSE OF REVIEW: The overlap of neuropsychiatric illness and developmental
      disability continues to be prominently recognized in clinical practice and in the
      academic literature. Theoretical and practical considerations may represent a
      frontier for understanding brain and behavior relationships. The purpose of this
      review is to explore this common relationship and report on recent literature
      that helps advance the larger fields of psychiatry and neurology. RECENT
      FINDINGS: Overlap between developmental disability, epilepsy, and
      neuropsychiatric illness may be more common than originally thought. Excessive
      excitatory neurotransmitter activity may be present in epilepsy and in autism
      spectrum disorder. Specific seizure types may be associated with features of
      developmental disabilities and neuropsychiatric conditions. SUMMARY:
      Neuropsychiatric illness is common in epilepsy and more frequent in developmental
      disabilities than generally recognized. Seizure foci in the temporal lobe may
      play a significant role. Brain connectivity and specific neurotransmitter systems
      are active areas of investigation. Antiepileptic drugs may improve
      neuropsychiatric symptoms in persons with developmental disability and epilepsy.

PMID- 29227298
TI  - Advances, innovations, and challenges for new and old infections of children and
      adolescents.

PMID- 29227299
TI  - Blaise Pascal and the evidence on the use of multiple arterial grafts for
      coronary artery bypass surgery after the interim analysis of the Arterial
      Revascularization Trial.
AB  - PURPOSE OF REVIEW: After the publication of the interim analysis of the ART, we
      review the contradiction between the large numbers of observational studies
      published on the course of over 25 years and the randomized trials comparing the
      use of single versus multiple arterial grafts for coronary bypass surgery. RECENT
      FINDINGS: The Arterial Revascularization Trial (ART) found no difference in
      survival and event-free survival at 5 years between patients randomized to
      receive one or two internal thoracic arteries at the time of surgery. SUMMARY: At
      the moment, there is evidence that arterial grafts have higher patency rate than
      venous grafts and a possible protective effect on the coronary circulation.
      Arterial grafts are still a reasonable choice, especially in patients with long
      life expectancy. Further studies and the final results of ART are needed.

PMID- 29227300
TI  - Exercise testing in heart failure: a contemporary discussion in an era of novel
      diagnostic techniques and biomarkers.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent advances in
      the field of exercise testing for patients with heart failure. RECENT FINDINGS:
      The importance of assessment of cardiorespiratory fitness (CRF) and exercise
      testing in heart failure is highlighted in the consensus recommendation of the
      American Heart Association. Contemporary studies have validated the independent
      and incremental strength of CRF metrics in patients with heart failure and
      coronary artery disease. The use of respiratory gas analysis and imaging or
      hemodynamics during physical exercise is feasible and results in high prognostic
      utility across the continuum of heart failure. Understanding how CRF metrics
      complement existing and novel biomarkers and risk scores is an emerging subject
      of scientific inquiry. SUMMARY: In the current era of personalized medicine,
      integrating CRF, imaging and circulating biomarkers will allow us to further
      develop individualized strategies for improving outcome in patients with heart
      failure.

PMID- 29227301
TI  - Palliative care in gynecologic oncology.
AB  - PURPOSE OF REVIEW: Patients with gynecologic malignancies face many difficult
      issues in the course of their diseases, ranging from physical symptoms to advance
      care planning in light of a poor prognosis. This review examines the evidence
      supporting integration of palliative care early in the course of disease and
      symptom management, and provides a framework for difficult conversations. RECENT
      FINDINGS: Palliative care has been demonstrated to improve quality of life and
      promote survival if integrated early in the course of disease. An evidence-based
      approach should guide symptom management, such as pain and nausea. Advance care
      planning and goals of care discussions are enhanced by a framework guiding
      discussion and the incorporation of empathetic responses. SUMMARY: Palliative
      care is a diverse multidisciplinary field that can provide significant benefit
      for patients with gynecologic malignancies.

PMID- 29227302
TI  - The target invites a foe: antibody-drug conjugates in gynecologic oncology.
AB  - PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) represent a promising new
      class of cancer therapeutics. Currently more than 60 ADCs are in clinical
      development, however, only very few trials focus on gynecologic malignancies. In
      this review, we summarize the most recent advances in ADC drug development with
      an emphasis on how this progress relates to patients diagnosed with gynecologic
      malignancies and breast cancer. RECENT FINDINGS: The cytotoxic payloads of the
      majority of the ADCs that are currently in clinical trials for gynecologic
      malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1,
      DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and
      noncleavable linkers are currently being investigated in clinical trials. A
      number of novel target antigens are currently being validated in ongoing clinical
      trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3,
      protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most
      ADCs currently in clinical development, dose-limiting toxicities appear to be
      unrelated to the targeted antigen but more tightly associated with the payload.
      Rational drug design involving optimization of the antibody, the linker and the
      conjugation chemistry is aimed at improving the therapeutic index of new ADCs.
      SUMMARY: Antibody-drug conjugates can increase the efficacy and decrease the
      toxicity of their payloads in comparison with traditional cyctotoxic agents. A
      better and quicker translation of recent scientific advances in the field of ADCs
      into rational clinical trials for patients diagnosed with ovarian, endometrial or
      cervical cancer could create real improvements in tumor response, survival and
      quality of life for our patients.

PMID- 29227303
TI  - Alternative facts and morcellation.
AB  - PURPOSE OF REVIEW: Since the recent black-box warning regarding the use of
      electromechanical morcellation, there has been a hesitancy to utilize the product
      and even to perform other types of morcellation by gynecologists. Unfortunately,
      this Food and Drug Administration action and the continued public criticisms of
      this procedure are grounded in poor data and faulty reasoning. To truly perform
      informed consent to patients considering procedures involving morcellation, a
      thorough review of the facts, not alternative facts, must be communicated. RECENT
      FINDINGS: Misrepresentation of the ethics surrounding this procedure, the role of
      informed consent and the risks and benefits as determined by evidence-based
      medicine have led to confusion and poor public policy. Today's evidence suggests
      that the procedure is indeed ethical when full disclosure of the risks and
      benefits is presented via informed consent. Risks of the procedure have been
      exaggerated significantly, and little attention has been paid to the risks of
      denying morcellation procedures to patients. Attempts to condemn gynecologists as
      acting contrary to established surgical principles do not coincide with facts.
      SUMMARY: Morcellation is a controversial technique which undoubtedly has a role
      as well as limitations. To appropriately determine if the procedure is indicated
      and acceptable to the patient, full disclosure of the best available evidence is
      necessary.

PMID- 29227304
TI  - Cell-based immunotherapy in gynecologic malignancies.
AB  - PURPOSE OF REVIEW: To provide an overview of the principles, safety and efficacy
      of adoptive cell therapy (ACT) in solid tumors particularly in gynecological
      cancers. RECENT FINDINGS: Efforts to target solid tumors using tumor-infiltrating
      lymphocytes and genetically modified T cells have shown promising efficacy in
      some patients. Two food and drug administration approvals for the treatment of
      leukemia are the first gene therapies available for cancer treatment in the
      United States. SUMMARY: Genetic engineering of antitumor immunity using T cells
      has the potential to target specific tumor-associated antigens and overcome
      obstacles to successful immunotherapy like immune-suppressive factors in the
      tumor microenvironment.

PMID- 29227305
TI  - Lung transplantation for chronic obstructive pulmonary disease: past, present,
      and future directions.
AB  - PURPOSE OF REVIEW: Lung transplantation offers an effective treatment modality
      for patients with end-stage chronic obstructive pulmonary disease (COPD). The
      exact determination of when to refer, list, and offer transplant as well as the
      preferred transplant procedure type remains unclear. Additionally, there are
      special considerations specific to patients with COPD being considered for lung
      transplantation, including the implications of single lung transplantation on
      lung cancer risk, native lung hyperinflation, and overall survival. RECENT
      FINDINGS: The International Society for Heart and Lung Transplantation's most
      recent recommendations rely on an assessment of COPD severity based on BODE
      index. Despite the lack of evidence supporting a mortality benefit of bilateral
      over single lung transplantation for COPD patients, the majority of transplants
      performed in this population remain bilateral. Some of the concerns specific to
      single lung transplantation remain the possibility of de novo native lung cancer
      and the hemodynamic and physiologic implications of acute native lung
      hyperinflation. SUMMARY: COPD remains the most common worldwide indication for
      lung transplantation. Ongoing study is still required to assess the overall
      survival benefit of lung transplantation and assess the overall quality of life
      impact on the COPD patient population.

PMID- 29227307
TI  - A patient with chromosome 18p deletion and congenital hypoglossia.

PMID- 29227308
TI  - Medical bioinformatics in melanoma.
AB  - PURPOSE OF REVIEW: Bioinformatic insights from next-generation sequencing has
      been integral in understanding melanoma biology, resistance to treatment and
      provided new avenues for melanoma treatment. Whole-genome sequencing, whole-exome
      sequencing and RNA sequencing has redefined the molecular classification of
      melanoma, revealed distinct genetic aberrations that define clinical subtypes of
      melanoma and uncovered the diverse heterogeneity that resides in an individual
      tumor. RECENT FINDINGS: In this review, we will summarize the recent whole-genome
      study that catalogs the genomic landscape across many melanoma subtypes, the
      single-cell RNA sequencing studies that interrogates tumor heterogeneity and the
      personalized vaccine approaches to melanoma treatment. SUMMARY: Whole-genome
      sequencing of diverse subtypes of melanoma revealed acral and mucosal subtypes to
      have a different genomic landscape compared with cutaneous melanoma. Acral and
      mucosal melanomas are characterized by low mutation burden and high structural
      variants. Single-cell RNA sequencing revealed high intratumoral heterogeneity and
      the existence of rare intrinsic drug-resistant populations. Lastly, vaccination
      against tumor neoantigens could be a potential personalized medicine therapy for
      melanoma patients. In summary, bioinformatics research is deeply ingrained in all
      aspects of melanoma research and will continue to blossom together for many years
      to come.

PMID- 29227306
TI  - Big Data Analytical Approaches to the NACC Dataset: Aiding Preclinical Trial
      Enrichment.
AB  - BACKGROUND: Clinical trials increasingly aim to retard disease progression during
      presymptomatic phases of Mild Cognitive Impairment (MCI) and thus recruiting
      study participants at high risk for developing MCI is critical for cost-effective
      prevention trials. However, accurately identifying those who are destined to
      develop MCI is difficult. Collecting biomarkers is often expensive. METHODS: We
      used only noninvasive clinical variables collected in the National Alzheimer's
      Coordinating Center (NACC) Uniform Data Sets version 2.0 and applied machine
      learning techniques to build a low-cost and accurate Mild Cognitive Impairment
      (MCI) conversion prediction calculator. Cross-validation and bootstrap were used
      to select as few variables as possible accurately predicting MCI conversion
      within 4 years. RESULTS: A total of 31,872 unique subjects, 748 clinical
      variables, and additional 128 derived variables in NACC data sets were used.
      About 15 noninvasive clinical variables are identified for predicting
      MCI/aMCI/naMCI converters, respectively. Over 75% Receiver Operating
      Characteristic Area Under the Curves (ROC AUC) was achieved. By bootstrap we
      created a simple spreadsheet calculator which estimates the probability of
      developing MCI within 4 years with a 95% confidence interval. CONCLUSIONS: We
      achieved reasonably high prediction accuracy using only clinical variables. The
      approach used here could be useful for study enrichment in preclinical trials
      where enrolling participants at risk of cognitive decline is critical for proving
      study efficacy, and also for developing a shorter assessment battery.

PMID- 29227309
TI  - The Basic Science and Molecular Mechanisms of Lung Injury and Acute Respiratory
      Distress Syndrome.

PMID- 29227310
TI  - Preoperative Risk Assessment of Respiratory Failure.

PMID- 29227311
TI  - Perioperative Transfusion-Related Acute Lung Injury.

PMID- 29227312
TI  - Clinical Implications of Hyperoxia.

PMID- 29227313
TI  - Intraoperative Lung-protective Ventilation.

PMID- 29227314
TI  - One-Lung Ventilation and Acute Lung Injury.

PMID- 29227315
TI  - Inhaled Anesthetics in Acute Lung Injury.

PMID- 29227318
TI  - Will demand for PAs remain strong?

PMID- 29227316
TI  - Ventilatory Strategies in the Brain-injured Patient.

PMID- 29227319
TI  - A systems-based approach to patient care after liver transplantation.
AB  - Liver transplantation is a cure to many devastating acute and end-stage liver
      diseases. In the immediate postoperative period, patients are prone to graft, end
      organ, and immunosuppressive complications. This article reviews the causes,
      diagnosis, and treatment of acute postoperative liver transplant complications.

PMID- 29227320
TI  - Plantar fasciitis: A review of treatments.
AB  - Plantar fasciitis is the most common cause of heel pain in the United States.
      Many treatments are available and differ in efficacy and cost. This article
      discusses the theorized causes for plantar fasciitis and various treatments.

PMID- 29227321
TI  - An Innovative Model for Naloxone Use Within an OTP Setting: A Prospective Cohort
      Study.
AB  - OBJECTIVES: Unintentional opioid overdose deaths are a public health crisis, and
      naloxone is the most effective harm reduction tool to curb many of these deaths.
      There is growing evidence that take-home naloxone can prevent opioid overdose in
      targeted populations. The goal of this study is to measure the opioid overdose
      reversal rate with take-home naloxone among participants with a diagnosis of
      opioid use disorder (OUD) in an opioid treatment program (OTP) setting. METHODS:
      Patients enrolled in an outpatient OTP program were eligible for this prospective
      cohort study between April 4, 2016 and July 4, 2016. Two hundred forty-four study
      participants received overdose education, instruction on how to use naloxone, and
      were provided with 2 doses of a take-home naloxone auto-injector kit. They were
      subsequently followed for 3 months. RESULTS: Thirty-one study participants
      reported overdose reversals using naloxone auto-injector kits on 38 community
      members. All overdose reversals were heroin-related. Eighty-seven per cent of the
      community members reversed with naloxone were friends or relatives of the study
      participants. CONCLUSIONS: This study validates that naloxone is not commonly
      used on the index study participant, but is often used on a secondary target
      among people who inject drugs. The large number of overdose reversals reported in
      this prospective study suggests that this novel model for naloxone use may be
      replicated at other OTP settings to reduce opioid overdose deaths.

PMID- 29227323
TI  - Small-Scale Sustainable Water Project Decreases Infections, Complements Short
      Term Medical Missions.
AB  - Many communities in developing countries do not have access to clean water, which
      is essential to health. This project involved the installation of clean water
      filters in two rural Guatemalan villages, a small-scale sustainable community
      project proposed by a short-term medical mission team and accomplished in
      partnership with local missionaries. The percentage of infections in adult
      visitors to medical clinics was assessed pre- and post-installation of filters,
      and although not statistically significant, decreased.

PMID- 29227322
TI  - No Clear Benefit of Chlorhexidine Use at Home Before Surgical Preparation.
AB  - INTRODUCTION: Several studies have evaluated the efficacy of home use of
      chlorhexidine before surgery to reduce bacterial colonization. However, these
      studies have provided conflicting evidence about the potential efficacy of this
      strategy in decreasing bacterial loads and infection rates across surgical
      populations, and no prior study has analyzed the benefit of this intervention
      before spine surgery. We prospectively analyzed the effectiveness of
      chlorhexidine gluconate wipes for decreasing bacterial counts on the posterior
      neck. METHODS: Sixteen healthy adults participated in this prospective study. The
      right side of each participant's neck was wiped twice (the night before and the
      morning of the experiment) with chlorhexidine gluconate wipes. The left side was
      used as the control region. Bacterial swabs were obtained as a baseline upon
      enrollment in the study, then upon arrival at the hospital, and, finally, after
      both sides of the neck had received standard preoperative scrubbing. RESULTS: All
      patients had positive baseline bacterial growth (median >1,000 colonies/mL). When
      chlorhexidine gluconate wipes were used, decreased bacterial counts were noted
      before the preoperative scrub, but this finding was not statistically significant
      (P = 0.059). All patients had zero bacteria identified on either side of their
      neck after completion of the preoperative scrub. CONCLUSION: At-home use of
      chlorhexidine gluconate wipes did not decrease the topical bacterial burden.
      Therefore, using chlorhexidine gluconate wipes at home before surgery may offer
      no added benefit.

PMID- 29227324
TI  - Three-Dimensional Evaluation on the Effect of Maxillary Dentition Distalization
      With Miniscrews Implanted in the Infrazygomatic Crest.
AB  - OBJECTIVE: To evaluate the effect of the maxillary dentition distalization with
      miniscrews implanted in the infrazygomatic (IZ) crest with 3D reconstruction
      module from cone-beam computed tomography (CBCT). METHODS: Twenty patients who
      previously underwent dentition distalization treatment with miniscrews were
      recruited. A total of 40 images were obtained using CBCT, taken immediately
      before placement of the miniscrew anchorage and at the end of distalization. The
      3D-line measurements were recorded to monitor dental changes. RESULTS: There was
      significant movement of maxillary dentition before and after treatment with
      miniscrews. The miniscrews induced maxillary dentition distalization and
      corrected Class II relationship in 8 months on average. The incisors were
      retracted 4.3 mm and extruded 3.8 mm at the crown on average. The crown of
      canines showed 3.7 mm of distalization and the width increased by 3.1 mm
      averagely. The mesial buccal cusp of first molars' crowns showed 3.5-mm
      distalization and 2.1-mm intrusion, and the width increased by 5.0 mm averagely.
      The distal buccal cusp of first molars' crowns showed 2.8-mm distalization and
      3.7-mm intrusion, and the width increased by 6.2 mm averagely. CONCLUSIONS: The
      anchorage of miniscrews implanted in the IZ crest is an efficient device for
      maxillary dentition distalization.

PMID- 29227325
TI  - Study of Insulin Resistance in Patients With beta Thalassemia Major and Validity
      of Triglyceride Glucose (TYG) Index.
AB  - Complications like impaired glucose tolerance and diabetes mellitus due to iron
      overload need early identification in thalassemia. We studied the proportion of
      insulin resistance in thalassemia major patients on chronic transfusion,
      identified insulin resistance using homeostasis model assessment of insulin
      resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and
      validated TYG index. In total, 73 thalassemia patients on regular transfusion for
      3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting
      blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG
      index calculated and analyzed. Mean fasting glucose, triglyceride, and serum
      insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean
      serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of
      thalassemia patients and showed increase with age and serum ferritin. Insulin
      resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of
      4.3. Using receiver operating charecteristic curve analysis, it was found that,
      by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from
      39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value
      of 4.0215 for TYG index for better sensitivity and specificity in identifying
      insulin resistance.

PMID- 29227326
TI  - Sudden Intracranial Hemorrhage in a Patient With Atypical Chronic Myeloid
      Leukemia in Chronic Phase.
AB  - A 16-year-old boy was incidentally found to have hyperleukocytosis during a
      school physical examination. He was diagnosed with atypical chronic myeloid
      leukemia in chronic phase. Although treatment with hydoxyurea was started, his
      white blood cell count increased and he eventually developed lethal intracranial
      hemorrhage. Although very rare, intracranial hemorrhage should be considered as a
      possible complication in patients with atypical chronic myeloid leukemia, even in
      chronic phase, if they have hyperleukocytosis and thrombocytopenia.

PMID- 29227327
TI  - Effect of nutritional risk on short-term outcomes after laparoscopic-assisted
      gastrectomy: a prospective study from two centers.
AB  - BACKGROUND/AIM: The aim of this prospective double-center study was to explore
      the effect of nutritional risk on short-term outcomes in the patients who had
      gastric cancer and underwent a laparoscopic-assisted gastrectomy. PATIENTS AND
      METHODS: We conducted a study of patients who underwent laparoscopic-assisted
      gastrectomy in two large centers between June 2014 and April 2017. Patients'
      demographic and clinical characteristics and postoperative short-term outcomes
      were prospectively analyzed. Patients were divided into two groups depend on the
      preoperative presence of nutritional risk. Clinical variables were compared.
      Univariate analyses and multivariate logistic regression analyses evaluating the
      risk factors for postoperative complications were performed. RESULTS: A total of
      256 patients, comprising 187 males and 69 females, met the inclusion criteria and
      were included in this study. The mean age was 61.81 years, the average BMI was
      22.44 kg/m, and the average preoperative serum albumin was 39.42 g/l. Older age
      (P=0.001), higher tumor stage (P=0.047), lower BMI (P<0.001), lower preoperative
      serum albumin (P=0.005), and lower hemoglobin (P=0.013) were more common in the
      nutritional risk group. There were no significant differences in the short-term
      postoperative outcomes between nutritional risk and non-nutritional risk groups.
      Advanced age (P=0.024) and hypoalbuminemia (P=0.004) were independent risk
      factors for postoperative complications after laparoscopic-assisted gastrectomy.
      CONCLUSION: Nutritional risk may not be a clinical predictor of short-term
      outcomes after laparoscopic-assisted gastrectomy. Advanced age and preoperative
      hypoalbuminemia were independent risk factors for grade II or more postoperative
      complications.

PMID- 29227328
TI  - Limitations of teaching endoscopy.
AB  - BACKGROUND AND AIM: Endoscopic procedures of the gastrointestinal tract represent
      a category of diagnostic tests that considerably rely on skills and dexterity of
      a human tester. The present analysis aimed to delineate factors that affect the
      success of teaching endoscopy and potentially limit the acquisition of new skills
      and knowledge. METHODS: The performance of the endoscopist is described in terms
      of sensitivity and specificity. The outcomes of sequential testing and
      acquisition of new knowledge are calculated using matrix algebra. Teaching is
      modeled as an iterative process with an incremental improvement in a fellow's
      performance matrix. RESULTS: As a diagnostician, an endoscopist cannot measure
      beyond his/her own level of competence. The cognition and endoscopic skills of
      both the fellow and the attending physician determine how fast the fellow's
      endoscopic performance improves over time. The better the fellow's and the
      attending's abilities are to recognize and amend residual deficiencies, the
      faster the fellow's endoscopic performance improves. Severe or even complete
      diagnostic incompetence by either party can draw out the training process or even
      result in a complete standstill, respectively. CONCLUSION: The description of
      endoscopic performance in terms of test characteristics provides valuable
      insights into the influence of endoscopic performance characteristics on the
      outcome of endoscopy and on the constraints of teaching endoscopic skills.

PMID- 29227329
TI  - A systematic review and meta-analysis of second-line immunosuppressants for
      autoimmune hepatitis treatment.
AB  - INTRODUCTION: The gold-standard treatment for autoimmune hepatitis (AIH) is a
      prednisone/azathioprine combination. However, subgroups of patients may be
      unresponsive to this treatment. The aim of this study is to evaluate the efficacy
      of second-line immunosuppressive therapies for AIH through a systematic review
      and meta-analysis in adult patients. PATIENTS AND METHODS: The systematic review
      was registered at the PROSPERO platform under number 42015019831. Databases
      MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used
      were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms
      were linked with each immunosuppressant of interest. RESULTS: A total of 1532
      studies were identified. Of these, 1492 were excluded on the basis of title and
      abstract reading. Among the 40 studies retrieved for detailed full-text analysis,
      a total of 15 fulfilled the inclusion criteria for the analysis. The most studied
      second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction
      of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for
      cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For
      MM/prednisone, the mean rate of histological remission was 88.6%, liver
      transplantation was indicated in 11.4%, and the mortality rate was 7.2%.
      Limitations were also present, such as the lack of randomized-controlled trials
      and prospective studies, the small number of patients, and the heterogeneity
      between remission criteria. CONCLUSION: This is the first systematic review and
      meta-analysis to compare the second-line imunossupressant therapy for AIH. The
      most studied second-line immunosuppressive is the MM, with a reasonable
      histological remission. The use of combined tacrolimus/prednisone was the most
      effective for the normalization of aminotransferases.

PMID- 29227330
TI  - Total bile acid levels are associated with left atrial volume and cardiac output
      in patients with cirrhosis.
AB  - BACKGROUND AND AIMS: Bile acids (BAs) are potent signaling molecules involved in
      the regulation of several metabolic and functional aspects of cardiovascular
      homeostasis. BA pool alteration in cirrhosis may contribute toward the
      development of hemodynamic and cardiac disturbances. We aimed to investigate the
      association between total BA levels and echocardiographic and biochemical markers
      of cardiac dysfunction in cirrhotic patients. METHODS: Cirrhotic patients were
      enrolled prospectively in this hypothesis-generating study and evaluated for
      cardiac and hemodynamic dysfunction through clinical, echocardiographic, and
      biochemical means. Associations between total serum BA concentrations and markers
      of systolic or diastolic dysfunction and the presence of cirrhotic cardiomyopathy
      were tested through univariate and multivariate analyses. RESULTS: Fifty-eight
      patients with cirrhosis were assessed in this monocentric study. 49 (85%)
      patients had decompensated cirrhosis according to the Child class. The median
      total BA level was 45 umol/l. There was no correlation between BA levels and the
      etiology of cirrhosis (P=0.2), current alcohol use (P=0.8), sex (P=0.1), smoking
      status (P=0.2), age, or BMI. Systolic and diastolic dysfunction were rare in the
      cohort. Total BA levels associated with several echocardiographic parameters of
      the hyperdynamic syndrome in univariate analysis but only with left atrial volume
      in multivariate analysis (P=0.007). BA concentrations did not differ according to
      the presence of echocardiographically diagnosed cirrhotic cardiomyopathy in the
      two models tested. CONCLUSION: Total serum BA levels are associated with enlarged
      left atrial volume and markers of the hyperdynamic circulation in patients with
      cirrhosis irrespective of the etiology or the severity of liver disease.

PMID- 29227331
TI  - Unravelling new pathways of sterol metabolism: lessons learned from in-born
      errors and cancer.
AB  - PURPOSE OF REVIEW: To update researchers of recently discovered metabolites of
      cholesterol and of its precursors and to suggest relevant metabolic pathways.
      RECENT FINDINGS: Patients suffering from inborn errors of sterol biosynthesis,
      transport and metabolism display unusual metabolic pathways, which may be major
      routes in the diseased state but minor in the healthy individual. Although
      quantitatively minor, these pathways may still be important in healthy
      individuals. Four inborn errors of metabolism, Smith-Lemli-Opitz syndrome,
      cerebrotendinous xanthomatosis and Niemann Pick disease types B (NPB) and C (NPC)
      result from mutations in different genes but can generate elevated levels of the
      same sterol metabolite, 7-oxocholesterol, in plasma. How this molecule is
      metabolized further is of great interest as its metabolites may have an important
      role in embryonic development. A second metabolite, abundant in NPC and NPB
      diseases, cholestane-3beta,5alpha,6beta-triol (3beta,5alpha,6beta-triol), has
      recently been shown to be metabolized to the corresponding bile acid,
      3beta,5alpha,6beta-trihydroxycholanoic acid, providing a diagnostic marker in
      plasma. The origin of cholestane-3beta,5alpha,6beta-triol is likely to be 3beta
      hydroxycholestan-5,6-epoxide, which can alternatively be metabolized to the
      tumour suppressor dendrogenin A (DDA). In breast tumours, DDA levels are found to
      be decreased compared with normal tissues linking sterol metabolism to cancer.
      SUMMARY: Unusual sterol metabolites and pathways may not only provide markers of
      disease, but also clues towards cause and treatment.

PMID- 29227332
TI  - Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in
      Challenging Cases and in Limited Tissue and Cytologic Samples.
AB  - Mesothelial proliferations can be diagnostically challenging in small specimens,
      such as body fluid cytology and small tissue biopsies. A great morphologic
      challenge for pathologists is the separation of benign reactive mesothelial
      proliferations from malignant mesotheliomas. Reactive mesothelial proliferations
      may have histologic features that resemble malignancy including increased
      cellularity, cytologic atypia, and mitoses. Recent advances in mesothelioma
      genetics resulted in identification of BAP1 mutations and p16 deletions as
      features of malignant mesotheliomas. Hence, BAP1 immunohistochemistry and
      fluorescence in situ hybridization for p16 emerged as 2 most common
      diagnostically helpful ancillary studies used on limited samples when the
      question is whether the proliferation is malignant or benign. In contrast,
      separation of mesothelioma from other malignancies is relatively straight forward
      using morphology and immunohistochemical stains. The choice of antibody panel to
      be applied in an individual case is driven by morphology, either epithelioid or
      sarcomatoid. This brief review will focus on morphology and ancillary testing of
      mainly pleural mesothelial proliferations.

PMID- 29227333
TI  - Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA
      mutations in liquid biopsies of metastatic melanoma patients who gained clinical
      benefits from anti-PD1 antibody therapy.
AB  - Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of
      metastatic melanoma patients. Predictive or monitoring biomarkers for response to
      this therapy could improve the clinical management of these patients. To date, no
      established biomarkers are available for monitoring the response to
      immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as
      BRAF and NRAS mutations for melanoma patients have been proposed for monitoring
      of immunotherapy response. We present seven illustrative cases for the use of
      ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described
      exemplify four distinct clinical benefit patterns: rapid and durable complete
      response (CR), early progression, followed by CR, CR followed by early
      progression after interrupting treatment and long-term disease stabilization.
      These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring
      during anti-PD1 therapy is informative and can be of added value for the
      monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment.
      An important advantage of our approach is that using the cartridge system on the
      Idylla platform for mutation analysis, the results become available the same day
      2 h after plasma collection. Therefore, in the future, the ctDNA level can be an
      element in the clinical management of the patients.

PMID- 29227334
TI  - Quantitative assessment of neuropilin-2 as a simple and sensitive diagnostic
      assay for spitzoid melanocytic lesions.
AB  - There is a significant need for the development of diagnostic tools that can
      precisely distinguish Spitz nevi and spitzoid melanomas. Here, we report the
      development of a PCR-based quantitative diagnostic assay for spitzoid melanocytic
      lesions utilizing the expression ratio of neuropilin-2 and melan-A genes in
      primary tumor specimens. We find that the expression ratio of neuropilin-2/melan
      A is significantly increased in spitzoid melanomas compared with Spitz nevi. The
      diagnostic potential of this quantitative assay was validated in two independent
      sets of patient samples as demonstrated in a receiver operating characteristic
      curve analysis showing an area under the curve value of 91.8%. Furthermore, the
      assay was found to quantitatively distinguish the clinical nature of atypical
      spitzoid melanocytic lesions that were diagnostically undetermined using
      histopathologic criteria alone. Our data indicate that this quantitative assay
      may be used as a tool in determining the diagnostic classification of
      histologically challenging spitzoid tumors.

PMID- 29227335
TI  - Usefulness of the Braden Scale in Intensive Care Units: A Study Based on
      Electronic Health Record Data.
AB  - Nurses working in intensive care units have expressed concern that some
      categories of the Braden scale such as activity and nutrition are not suitable
      for intensive care unit patients. Upon examining the validity of the Braden scale
      using the electronic health data, we found relatively low predictability of the
      tool. Risk factors from the sensory perception and activity categories were not
      associated with risk of pressure ulcers.

PMID- 29227336
TI  - Family Caregivers' Experiences of Within-Hospital Handoffs for Older Adults in
      Acute Care.
AB  - Family caregivers' experiences during within-hospital handoffs between acute care
      units are not well understood. Qualitative description methodology was employed
      to describe family caregivers' experiences during their loved ones' handoffs.
      Semistructured interviews were conducted with 10 caregivers of hospitalized older
      adults. Three themes emerged: Lack of care coordination, Muddling through
      handoffs alone, and Wariness toward the care delivery system. Findings can help
      clinicians shape their interactions with caregivers to maximize their involvement
      in post-hospital care.

PMID- 29227337
TI  - Six Nursing Care Problems in Hospitals: A Cross-Sectional Study of Quality of
      Care.
AB  - BACKGROUND: Investigations on the quality of nursing care relating to various
      care problems are rare. PURPOSE: This study assessed the (1) fulfillment of
      structural indicators, (2) application of nursing interventions as process
      indicators, and (3) prevalence rate as outcome indicators with regard to various
      care problems. METHODS: A cross-sectional multicenter study was conducted in 30
      Austrian hospitals with 2878 patients. RESULTS: The highest number of structural
      quality indicators was fulfilled for pressure ulcers, falls, restraints, and
      pain. In malnutrition and urinary incontinence, a lack of structural indicators
      was observed. Most interventions were offered to patients with pressure ulcers or
      those who had experienced a fall. The lowest frequency of nursing interventions
      was seen in malnourished and incontinent persons. CONCLUSION: There is a need for
      the national adaptation of guidelines for malnutrition and urinary incontinence.
      This may increase the frequency of evidence-based nursing interventions.

PMID- 29227338
TI  - Associations Between Early Family Meal Environment Quality and Later Well-Being
      in School-Age Children.
AB  - OBJECTIVE: Past research suggests a positive link between family meals and child
      and adolescent health. Although researchers have often relied on how often
      families eat together, this may not capture the complexity of the experience.
      Using a birth cohort, this study examines the prospective associations between
      the environmental quality of the family meal experience at age 6 years and child
      well-being at age 10. METHODS: Participants are 1492 children of the Quebec
      Longitudinal Study of Child Development. When children were age 6, parents
      reported on their typical family meal environment quality. At age 10, parents,
      teachers, and children themselves provided information on lifestyle habits,
      academic achievement, and social adjustment, respectively. The relationship
      between early family meal environment quality and later child outcomes was
      analyzed using a series of multivariate linear regression. RESULTS: Family meal
      environment quality at age 6 predicted higher levels of general fitness and lower
      levels of soft drink consumption, physical aggression, oppositional behavior,
      nonaggressive delinquency, and reactive aggression at age 10. These relationships
      were adjusted for child characteristics (sex, temperament problems and cognitive
      abilities, and baseline body mass index [BMI]) and family characteristics (family
      configuration and functioning, maternal education, depression, and BMI).
      CONCLUSION: From a population-health perspective, our findings suggest that
      family meals have long-term influences on children's biopsychosocial well-being.
      At a time when family meal frequency is on a natural decline in the population,
      this environmental characteristic can become a target of home-based interventions
      and could be featured in information campaigns that aim to optimize child
      development.

PMID- 29227339
TI  - Comparison of Sulfur Hexafluoride (SF6) and Air Tamponade in Noniridectomized
      Descemet Membrane Endothelial Keratoplasty.
AB  - PURPOSE: To compare the efficacy and safety of 20% sulfur hexafluoride gas (SF6)
      and air tamponade in patients who underwent noniridectomized Descemet membrane
      endothelial keratoplasty (DMEK). METHODS: A retrospective chart review of
      patients who underwent DMEK with either air or SF6 tamponade: 41 eyes received
      air tamponade (group 1) and 41 received SF6 tamponade (group 2). Best spectacle
      corrected visual acuity, endothelial cell density, and complications including
      graft detachment and elevated intraocular pressure were compared. RESULTS: The
      mean follow-up time was 8 +/- 4 months in group 1 and 3 +/- 2 months in group 2.
      Mean best spectacle-corrected visual acuity improved from 1.12 +/- 0.88 to 0.64
      +/- 0.78 logarithm of the minimum angle of resolution (logMAR) in group 1 (P =
      0.009) and from 1.00 +/- 0.78 to 0.62 +/- 0.53 logMAR in group 2 (P = 0.006). The
      graft detachment rate was 39% (16 eyes) in group 1 and 42% (17 eyes) in group 2
      (P = 0.822). The rate of graft detachment larger than one third of the graft area
      was 17% in group 1 and 20% in group 2 (P = 0.775). Rebubbling was performed in
      26.8% and 20% of eyes in group 1 and 2, respectively (P = 0.43). Average
      endothelial cell loss was 32% in group 1 and 33% in group 2 (P = 0.83). In the
      immediate postoperative period, elevated intraocular pressure was observed in 2
      eyes (5%) in group 1 and in 4 eyes (10%) in group 2 (P = 0.4). There was 1
      primary graft failure in each group. CONCLUSIONS: Use of air with it being
      readily available and short acting is a good method of Descemet membrane
      tamponade in noniridectomized DMEK.

PMID- 29227340
TI  - Corneal Transplantation in New Zealand 2000 to 2009.
AB  - PURPOSE: To quantify all minor/major adverse events in a large cohort of
      consecutive corneal transplants, particularly in respect to penetrating
      keratoplasty (PKP). METHODS: All corneal transplants in the Auckland region over
      a 10-year period (2000-2009) were identified through the New Zealand National Eye
      Bank. Relevant clinical records were assessed for this period and 2 years after.
      All intraoperative or postoperative adverse events/complications, visual acuity,
      and graft outcomes were recorded. RESULTS: Detailed data were available for 941
      (94.5%) of 996 procedures in the study period, including 834 PKPs, 73 deep
      anterior lamellar keratoplasties, 28 Descemet stripping endothelial
      keratoplasties, and 6 tectonic keratoplasties. Intraoperative adverse events
      occurred in 117 (12.4%) procedures, most commonly positive vitreous pressure
      (6.3%). Postoperative adverse events included elevated intraocular pressure
      (21.3%, >30 mm Hg), graft rejection (29.8%), suture-related complications
      (30.1%), dry eye (15.9%), epithelial defect (9.8%), wound compromise (3.4%),
      microbial keratitis (3.2%), and endophthalmitis (0.6%). At 2 years, 58.7% of eyes
      achieved best-corrected visual acuity of >=6/12 (20/40) and 69.6% achieved >=6/18
      (20/60). Graft survival at 2 years was 87.9%, 92.3%, and 100% for PKP, deep
      anterior lamellar keratoplasty, and Descemet stripping endothelial keratoplasty,
      respectively. CONCLUSIONS: In this study of 941 consecutive, principally
      penetrating, corneal transplants, adverse events were found to be more common
      than typically reported. In an era in which PKP is increasingly substituted by
      lamellar surgery, this provides useful insight into operative and postoperative
      adverse events in penetrating surgery.

PMID- 29227341
TI  - Characterization of Corneal Endothelial Injury During Penetrating Keratoplasty.
AB  - PURPOSE: To characterize corneal endothelial injury during penetrating
      keratoplasty in a controlled wet laboratory environment using human tissue. To
      identify potential areas or steps within surgery in which insult to the corneal
      endothelium may be most affected by trauma during routine penetrating
      keratoplasty. METHODS: Human donor corneas (n = 12) with intact endothelium
      underwent experimental penetrating keratoplasty. Endothelial injury was evaluated
      after each suture quartile using trypan staining, a validated modality for
      assessing endothelial injury. Insult was quantified using high-resolution
      photography and computer software. RESULTS: Statistical significance was found in
      the change in staining between quartiles as determined by repeated-measures
      analysis of variance (F3,11 = 5.83, P < 0.0044). A post hoc Tukey test indicated
      that the change in staining during the first quartile (3.38% +/- 0.5%) was
      significantly lower than the remaining quartiles at P < 0.021. The change in
      staining did not differ significantly between the second (8.36% +/- 1.2%), third
      (7.88% +/- 1.2%), and fourth (7.73% +/- 0.9%) quartiles at P > 0.97. CONCLUSIONS:
      Evidence from this investigation suggests that injury to the endothelium occurs
      most during the second quartile. This may be a promising area in which clinicians
      could target their efforts to avoid injury to this vital tissue layer for best
      surgical outcomes and graft longevity.

PMID- 29227343
TI  - Golgi fragmentation induced by overactivated cyclin-dependent kinase 5 is
      associated with isoflurane-induced neurotoxicity.
AB  - Overactivated cyclin-dependent kinase 5 (Cdk5) induces Golgi fragmentation, which
      interrupts the processing and trafficking of secretory cargo and subsequently
      synaptic plasticity and synaptogenesis, and even leads to neuronal cell death.
      Cdk5 overactivation and subsequent Golgi fragmentation are involved in many
      neurodegenerative diseases. However, whether isoflurane-induced neurotoxicity is
      relevant to aberrant Cdk5 activation and subsequent Golgi fragmentation remains
      unknown. In the present study, we explored the underlying molecular mechanisms of
      isoflurane-induced neurotoxicity in primary cultured hippocampal neurons. After
      treatment with 2% isoflurane for 6 h, immunofluorescence staining and
      transmission electron microscopy were used to examine the Golgi structure.
      Neuronal viability was evaluated using the 3-(4,5-dimethyithiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide (MTT) assay and TUNEL staining. Cdk5 activity was
      assessed using histone H1 as a substrate. Our results showed that Cdk5 activity
      and the number of fragmented Golgi increased significantly after isoflurane
      exposure. This was accompanied by an increase in neuronal death. Meanwhile,
      pharmacological inhibition of Cdk5 activity by 8 uM roscovitine alleviated
      isoflurane-induced Golgi fragmentation and neurotoxicity. Cumulatively, this
      study shows that aberrant Cdk5 activation-induced Golgi fragmentation is relevant
      to isoflurane neurotoxicity and indicates that a Cdk5 inhibitor may be a
      potential therapeutic candidate for the prevention of isoflurane-induced
      neurotoxicity. Video abstract: http://links.lww.com/WNR/A445.

PMID- 29227342
TI  - Eyelid Changes Related to Meibomian Gland Dysfunction in Early Middle-Aged
      Patients Using Topical Glaucoma Medications.
AB  - PURPOSE: To investigate the relationship between topical glaucoma medications and
      meibomian gland dysfunction (MGD) in early middle-aged patients with glaucoma.
      METHODS: In this cross-sectional study, 50 patients with glaucoma younger than 50
      years who had used topical glaucoma medications for more than 6 months and 40
      normal controls of similar age were included. Patients in each group were graded
      for MGD (0-4) using slit-lamp microscopy. Tear film breakup time (BUT), ocular
      surface staining, and Marx line scores were also evaluated. Differences between
      both groups were analyzed statistically. RESULTS: The prevalence of MGD was 82%
      in the group using topical glaucoma medications and 52.5% in the control group.
      The average period of topical glaucoma medication use was 27.4 months. There were
      significant differences in the breakup time and Marx line score according to the
      presence of MGD. Although the duration of topical glaucoma medication use and the
      severity of MGD did not show a significant correlation, the degree of MGD and the
      Marx line score were significantly correlated. CONCLUSIONS: Glaucoma eye drops
      may be one factor affecting the eyelid changes associated with MGD. The Marx line
      score may be used as an index to evaluate MGD in patients with glaucoma.

PMID- 29227345
TI  - Response: "Percutaneous Vascular Interventions Versus Bypass Surgeries in
      Patients With Critical Limb Ischemia".

PMID- 29227344
TI  - Predictors of Resectability and Survival in Patients with Borderline and Locally
      Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment with FOLFIRINOX.
AB  - OBJECTIVE: The aim of this study was to determine (1) whether preoperative
      factors can predict resectability of borderline resectable (BR) and locally
      advanced (LA) pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant
      FOLFIRINOX, (2) which patients might benefit from adjuvant therapy, and (3)
      survival differences between resected BR/LA patients who received neoadjuvant
      FOLFIRINOX and upfront resected patients. BACKGROUND: Patients with BR/LA PDAC
      are often treated with FOLFIRINOX to obtain a margin-negative resection, yet
      selection of patients for resection remains challenging. METHODS:
      Clinicopathologic data of PDAC patients surgically explored between 04/2011
      11/2016 in a single institution were retrospectively collected. RESULTS:
      Following neoadjuvant FOLFIRINOX, 141 patients were surgically explored (BR: 49%,
      LA: 51%) and 110 (78%) were resected. Resected patients had lower preoperative CA
      19-9 levels (21 vs 40 U/mL, P = 0.03) and smaller tumors on preoperative computed
      tomography (CT) scan (2.3 vs 3.0 cm, P = 0.03), but no predictors of
      resectability were identified. Median overall survival (OS) was 34.2 months from
      diagnosis for all FOLFIRINOX patients and 37.7 months for resected patients.
      Among resected patients, preoperative CA 19-9 >100 U/mL and >8 months between
      diagnosis and surgery predicted a shorter postoperative disease-free survival
      (DFS); Charlson comorbidity index >1, preoperative CA 19-9 >100 U/mL and tumor
      size (>3.0 cm on CT or >2.5 cm on pathology) predicted decreased OS. DFS and OS
      were significantly better for BR/LA PDAC patients treated with neoadjuvant
      FOLFIRINOX compared with upfront resected patients (DFS: 29.1 vs 13.7, P < 0.001;
      OS: 37.7 vs 25.1 months from diagnosis, P = 0.01). CONCLUSION: BR/LA PDAC
      patients with no progression on neoadjuvant FOLFIRINOX should be offered surgical
      exploration. Except size, traditional pathological parameters fail to predict
      survival among resected FOLFIRINOX patients. Resected FOLFIRINOX patients have
      survival that appears to be superior than that of resectable patients who go
      directly to surgery.

PMID- 29227346
TI  - Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast
      Cancer: Contemporary Practice Patterns and Survival Analysis.
AB  - OBJECTIVE: We evaluated patterns of surgical care and their association with
      overall survival among a contemporary cohort of women with stage IV breast
      cancer. BACKGROUND: Surgical resection of the primary tumor remains controversial
      among women with stage IV breast cancer. METHODS: Women diagnosed with clinical
      stage IV breast cancer from 2003 to 2012 were identified from the American
      College of Surgeons National Cancer Database. Those with intact primary tumors
      who were alive 12 months after diagnosis were categorized by treatment sequence:
      (1) surgery before systemic therapy, (2) systemic therapy before surgery, and (3)
      systemic therapy alone. Multivariate logistic regression was used to estimate the
      association of treatment sequence with surgery type. Overall survival was
      estimated using multivariate Cox proportional hazards models. RESULTS: Among
      24,015 women, 56.2% (13,505) underwent systemic therapy alone and 43.8% (10,510)
      underwent surgical resection. Rates of surgery decreased slightly over time
      (43.1% in 2003 to 41.9% in 2011). Treatment with systemic therapy before surgery
      was associated with larger tumor size (median 4.5 vs 3.1 cm, P < 0.001) and
      receipt of mastectomy (81.4% vs 52.2%, P < 0.001) when compared to those who
      underwent surgery first. Receipt of surgery, whether before or after systemic
      therapy (Hazard Ratio, 0.68; 95% confidence interval, 0.62-0.73; Hazard Ratio,
      0.56; 95% confidence interval, 0.52-0.61; P < 0.001), was independently
      associated with improved adjusted overall survival when compared to systemic
      therapy alone. CONCLUSIONS: Surgical resection of the primary tumor occurs in
      almost half of women with stage IV breast cancer alive 1 year after diagnosis,
      and is increasingly occurring after systemic therapy. Coordinated
      multidisciplinary care remains highly relevant in the setting of metastatic
      breast cancer, where surgical decisions should be made on an individual basis and
      may affect survival in select women.

PMID- 29227347
TI  - Surgeons as Part of the Solution: Changing the Culture of Opioid Prescribing.

PMID- 29227348
TI  - Quantitative PET/CT in clinical practice: assessing the agreement of PET tumor
      indices using different clinical reading platforms.
AB  - OBJECTIVE: The aim of this study was to determine whether various fluorine-18
      fluorodeoxyglucose PET/CT-derived parameters used in oncology vary significantly
      depending on the interpretation software systems used in clinical practice for
      multiple human solid tumors. PATIENTS AND METHODS: A total of 120 fluorine-18
      fluorodeoxyglucose PET/CT studies carried out in patients with pancreatic, lung,
      colorectal, and head and neck cancers were evaluated retrospectively on two
      different vendor software platforms including Mirada and MIMVista. Regions of
      interest were placed on the liver to determine the liver mean standardized uptake
      value at lean body mass (SUL) and on each tumor to determine the SULmax, SULpeak.
      Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were determined
      using fixed thresholds of 50% of SULmax and SULpeak. Inter-reader, intersystem
      intraclass correlations, systematic bias, and variability reflected by the 95%
      limits of agreement, and precision were determined. RESULTS: There was excellent
      inter-reader reliability between the readers and the two software systems, with
      intraclass correlations more than 0.9 for all PET metrics, with P values less
      than 0.0001. The bias and SD on Bland-Altman analysis between the two software
      platforms for tumor SULmax, SULpeak, Max50MTV, and Peak50MTV, respectively, for
      Reader 1 were -1.52+/-2.24, 0.80+/-3.67, -0.80+/-13.01, and -4.49+/-20.6. For
      Reader 2, the biases were -1.62+/-1.95, 0.18+/-3.60, -0.27+/-4.64, and -3.13+/
      8.30. The precision between the two systems was better for SULmax and SULpeak,
      with less variance observed, than for volume-based metrics such as Max50MTV and
      Peak50MTV or TLG. CONCLUSION: Excellent correlation has been found between two
      tested software reading platforms for all PET-derived metrics in a dual-reader
      analysis. Overall, the SULmax and SULpeak values had less bias and better
      precision compared with the MTV and TLG.

PMID- 29227349
TI  - SEVERE IMMUNE-MEDIATED THROMBOCYTOPENIA AFTER INTRAVITREAL BEVACIZUMAB INJECTION.
AB  - PURPOSE: To report a case of severe immune-mediated thrombocytopenia after
      intravitreal bevacizumab administration. METHODS: A 77-year-old man with right
      sided macular degeneration received intravitreal bevacizumab. After his third
      treatment dose, he was hospitalized for symptomatic thrombocytopenia (platelet
      count of 3 k/MUL) and underwent testing to determine the etiology. RESULTS:
      Initial platelet counts on admission were 3 k/MUL, down from 238 k/MUL 3 months
      before. A peripheral smear, coagulation studies, and an abdominal CT were
      unremarkable. A bone marrow biopsy revealed hypercellular marrow with
      megakaryocytic hyperplasia. Serum antiplatelet antibody testing identified
      antibodies against glycoprotein IV and human leukocyte antigens. A total of 13
      units of platelets were administered and resulted in no significant response.
      Treatment with rituximab, romiplostim, and human leukocyte antigen-matched
      platelets resulted in slow recovery and normalization of platelet counts.
      CONCLUSION: The case presented shows apparent severe immune-mediated
      thrombocytopenia after intravitreal bevacizumab administration.

PMID- 29227350
TI  - TAMOXIFEN RETINOPATHY DURING TREATMENT OF AN INOPERABLE DESMOID TUMOR.
AB  - PURPOSE: To evaluate the clinical significance and rarity of tamoxifen
      retinopathy after a long-term tamoxifen treatment for an inoperable desmoid
      tumor. METHODS: Case report. RESULTS: Tamoxifen retinopathy is a condition rarely
      observed in clinical practice. Although tamoxifen is typically a treatment for
      breast cancer patients, we present a 68-year-old woman taking tamoxifen for an
      inoperable desmoid tumor, an equally rare condition. She presented with
      bilaterally deteriorating vision over the course of a year. Fundoscopic
      examination revealed parafoveal deposits bilaterally. Spectral domain optical
      coherence tomography exhibited hyperreflective deposits in all layers of the
      retina. She had a cumulative treatment dose of 292 g of tamoxifen, and the
      medication was subsequently stopped. Her vision remained stable 3 months after
      the cessation of tamoxifen. CONCLUSION: The development of tamoxifen retinopathy
      in the treatment of a desmoid tumor makes this case a rare entity, and this is
      the first reported case of these two concomitant conditions to our knowledge.
      With the use of long-term tamoxifen as a primary treatment, we recommend
      screening at regular intervals by an ophthalmologist as an integral part of
      treatment.

PMID- 29227351
TI  - Impact of pectoral nerve block on postoperative pain and quality of recovery in
      patients undergoing breast cancer surgery: A randomised controlled trial.
AB  - BACKGROUND: In recent years, thoracic wall nerve blocks, such as the pectoral
      nerve (PECS) block and the serratus plane block have become popular for peri
      operative pain control in patients undergoing breast cancer surgery. The effect
      of PECS block on quality of recovery (QoR) after breast cancer surgery has not
      been evaluated. OBJECTIVES: To evaluate the ability of PECS block to decrease
      postoperative pain and anaesthesia and analgesia requirements and to improve
      postoperative QoR in patients undergoing breast cancer surgery. DESIGN:
      Randomised controlled study. SETTING: A tertiary hospital. PATIENTS: Sixty women
      undergoing breast cancer surgery between April 2014 and February 2015.
      INTERVENTIONS: The patients were randomised to receive a PECS block consisting of
      30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a
      saline mock block (control group). The patients answered a 40-item QoR
      questionnaire (QoR-40) before and 1 day after breast cancer surgery. MAIN OUTCOME
      MEASURES: Numeric Rating Scale score for postoperative pain, requirement for
      intra-operative propofol and remifentanil, and QoR-40 score on postoperative day
      1. RESULTS: PECS block combined with propofol-remifentanil anaesthesia
      significantly improved the median [interquartile range] pain score at 6 h
      postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P =
      0.018]. PECS block also reduced propofol mean (+/- SD) estimated target blood
      concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group
      2.65 (+/- 0.52) vs. Control group 3.08 (+/- 0.41) MUg ml; P < 0.001) but not
      remifentanil consumption (PECS group 10.5 (+/- 4.28) vs. Control group 10.4 (+/-
      4.68) MUg kg h; P = 0.95). PECS block did not improve the QoR-40 score on
      postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75
      to 175]). CONCLUSION: In patients undergoing breast cancer surgery, PECS block
      combined with general anaesthesia reduced the requirement for propofol but not
      that for remifentanil, due to the inability of the PECS block to reach the
      internal mammary area. Further, PECS block improved postoperative pain but not
      the postoperative QoR-40 score due to the factors that cannot be measured by
      analgesia immediately after surgery, such as rebound pain. TRIAL REGISTRATION:
      This trial is registered with the University Hospital Medical Information Network
      Clinical Trials Registry (UMIN000013435).

PMID- 29227352
TI  - Epidemiology of axial spondyloarthritis: an update.
AB  - PURPOSE OF REVIEW: To provide an update of the prevalence and incidence of axial
      spondyloarthritis in the general population and in patients with
      spondyloarthritis-related conditions, environmental risk factors for ankylosing
      spondylitis, progression from nonradiographic axial spondyloarthritis to
      ankylosing spondylitis, mortality, and risks for cardiovascular events in
      patients with ankylosing spondylitis. RECENT FINDINGS: Increasingly,
      administrative healthcare data have been used to study disease frequency and
      outcomes. The prevalence of ankylosing spondylitis ranged from 9 to 30 per 10 000
      persons, which are lower than previous estimates. Data on whether childhood
      infections influence the risk of ankylosing spondylitis were equivocal, while
      having been breast-fed may be protective. Progression of patients with
      nonradiographic axial spondyloarthritis to ankylosing spondylitis is slow, with
      estimates of 5.1% in 5 years and 19% in 10 years. Risk of mortality is slightly
      increased in ankylosing spondylitis. Risks for cardiovascular events in
      ankylosing spondylitis were either not different from, or only slightly higher
      than in controls. No studies have examined these outcomes in the broader group of
      patients with axial spondyloarthritis. SUMMARY: Expanded use of administrative
      and registry data has facilitated studies of the epidemiology of ankylosing
      spondylitis, but lack of specific diagnostic codes limits use of these resources
      for studying axial spondyloarthritis in general.

PMID- 29227354
TI  - Current views on the pathogenesis of Sjogren's syndrome.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an insight into the
      pathophysiological mechanisms involved in the pathogenesis of primary Sjogren's
      Syndrome (pSS), highlighting recent findings with potential therapeutic
      repercussions. RECENT FINDINGS: In the last 2 years, epigenetic analyses provided
      new insights into pSS pathogenesis. Characterization of DNA methylation patterns,
      chromatin structures and microRNA confirmed the importance of aberrant interferon
      and B-cell responses in the development of the disease. The formation of ectopic
      B-cell follicles with germinal centers is now a well recognized pathogenic
      mechanism within salivary glands of pSS. In the context of ectopic germinal
      centers reaction, T/B-cell interactions, that is regarding T-helper 17 and T
      follicular helper cells, and their respective counterparts, T-regulatory and T
      follicular regulatory cells, appear particularly relevant in pSS pathogenesis as
      their imbalance is associated with a dysregulation of B-cell dynamics and the
      production of autoantibodies. SUMMARY: Advances in the understanding of pSS
      pathogenesis have paved the way for clinical trials with novel biologic agents
      targeting immune pathways regulating T/B-cell interactions and downstream B-cell
      activation. Reverse translation from these studies provides invaluable novel
      information of the mechanisms sustaining autoimmunity and chronic inflammation in
      pSS.

PMID- 29227353
TI  - Epidemiology of osteoarthritis: literature update.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies of
      osteoarthritis epidemiology, including research on prevalence, disease impact,
      and potential risk factors. RECENT FINDINGS: Osteoarthritis is highly prevalent
      in the United States and around the globe. It is a leading cause of disability
      and can negatively impact people's physical and mental well being. Healthcare
      resources and costs associated with managing the disease can be substantial.
      There is increasing evidence that there are different osteoarthritis phenotypes
      that reflect different mechanisms of the disease. Various person-level risk
      factors are recognized, including sociodemographic characteristics (e.g. female
      sex, African-American race), genetic predispositions, obesity, diet-related
      factors, and high bone density/mass. Joint-level risk factors include specific
      bone/joint shapes, thigh flexor muscle weakness, joint malalignment,
      participation in certain occupational/sports activities, and joint injury. Recent
      studies have enhanced our understanding of preradiographic lesions associated
      with osteoarthritis. SUMMARY: Application of these new findings may allow us to
      develop innovative strategies and novel therapies with the purpose of preventing
      new disease onset and minimizing disease progression.

PMID- 29227355
TI  - Basic calcium phosphate crystal-associated musculoskeletal syndromes: an update.
AB  - PURPOSE OF REVIEW: Basic calcium phosphate (BCP) crystals are associated with two
      important musculoskeletal syndromes. Deposition of BCP crystals in tendons,
      bursae, and other soft tissues around joints causes calcific periarthritis,
      whereas intra-articular BCP crystals contribute to osteoarthritis and cause the
      highly destructive arthritis known as Milwaukee Shoulder Syndrome. The
      epidemiology and natural history of these syndromes are poorly understood, and
      because the pathogenesis remains unclear, few targeted therapies are available. I
      will review new developments in this field. RECENT FINDINGS: I will discuss a
      case collection of calcific periarthritis of the hip, and evidence-based
      management strategies for shoulder calcific periarthritis that might be applied
      to calcific periarthritis at other locations. I will summarize several recent
      articles addressing mechanisms of crystal formation and identifying pathways
      through which BCP crystals produce tissue damage and explore some newly
      identified risk factors for pathologic mineralization. SUMMARY: We are making
      slow, but steady progress in understanding the clinical presentation of calcific
      periarthritis in sites other than the shoulder. A growing appreciation of the
      mechanisms through which BCP crystals mediate tissue damage should lead to the
      development of novel management strategies for these common musculoskeletal
      syndromes.

PMID- 29227356
TI  - Novel advances on tissue immune dynamics in HIV/simian immunodeficiency virus:
      lessons from imaging studies.
AB  - PURPOSE OF REVIEW: To describe recent findings on the effect of HIV/SIV infection
      on lymph node viral and T-cell dynamics using imaging-based methodologies. RECENT
      FINDINGS: Chronic infection, particularly HIV/SIV, alters dramatically the
      microenvironment, immune cell frequency, distribution, function and tissue
      organization of secondary lymphoid tissues. These changes are not always
      reversible. Over the past few years, the implementation of advanced imaging
      protocols on human lymph node biopsies as well as on longitudinal lymphoid
      tissues samples from nonhuman primates (NHP) have provided a wealth of
      information on how local immune responses evolve over time in response to a
      persisting retroviral pathogen. Most of the information concerns cytotoxic and
      helper T cells and viral dynamics. In this review, we detail this information
      focusing on HIV/SIV infection. We also comment on the gaps that imaging
      technologies have bridged in our understanding and discuss the translational
      value of these new findings in the light of emerging therapeutic agendas.
      SUMMARY: Novel imaging platforms allow for dissecting the spatiotemporal dynamics
      of immune interactions further improving our understanding of the interplay
      between virus and host and providing important information for designing
      successful preventive and curative strategies.

PMID- 29227357
TI  - Risk Management Interventions to Reduce Injuries and Maximize Economic Benefits
      in U.S. Mining.
AB  - OBJECTIVE: Risk management (RM) is a cyclical process of identifying and ranking
      risks, implementing controls, and evaluating their effectiveness. This study aims
      to identify effective RM interventions in the U.S. mining industry. METHODS: RM
      interventions were identified in four companies representing metal, aggregate,
      and coal mining sectors. Injury rates were determined using Mine Safety and
      Health Administration (MSHA) data and changes in injury rates identified through
      change point analysis. Program implementation costs and associated changes in
      injury costs were evaluated for select interventions. RESULTS: Six of 20 RM
      interventions were associated with a decline in all injuries and one with a
      reduction in lost-time injuries, all with a positive return on investment.
      CONCLUSION: Reductions in injuries and associated costs were observed following
      implementation of a limited number of specific RM interventions.

PMID- 29227358
TI  - The Impact of Work Ability on Work Motivation and Health: A Longitudinal Study
      Based on Older Employees.
AB  - OBJECTIVE: Work participation is determined by work motivation and work ability
      with health as a significant component. Within the lidA-study, we explore the
      impact of work ability on work motivation and health with consideration of
      further influencing factors. METHODS: Four thousand one hundred nine older
      employees were interviewed two times (t0 = 2011, t1 = 2014). Two multivariate
      analyses were performed regarding the influence of work ability on work
      motivation (Model 1) and health (Model 2). RESULTS: Within the multivariate
      analysis, of all the influencing factors, work ability has the strongest effect
      on work motivation (F = 37.761) and health (F = 76.402). It appears as a decisive
      determinant for both dimensions. CONCLUSION: Regarding the results, it is useful
      to focus on the work ability of older employees in order to maintain and boost
      their work motivation and health.

PMID- 29227359
TI  - Is Employer-Directed Medical Care Associated With Decreased Workers' Compensation
      Claim Costs?
AB  - BACKGROUND: The financial impact regarding choice of physician within the
      workers' compensation domain has not been well studied. OBJECTIVE: The aim of
      this study was to assess the difference in claim cost between employee- and
      employer-directed choice of treating physician after injury. METHODS: Thirty-five
      thousand six hundred forty indemnity lost time claims from a 13-year period at a
      nationwide company were analyzed with multivariate logistic regression to
      determine the association of medical direction with risk of high-cost claims.
      RESULTS: States that have employer-directed physician choice were associated with
      a lower risk of having high-cost claims (>=$50,000) but higher attorney
      involvement than employee direction. The net effect of this enhanced presence of
      attorneys offsets the benefits of employer choice of treating physician.
      CONCLUSION: States that permit employer selection of treating physician have
      slightly higher cost due to the higher prevalence of attorney involvement in the
      claims process.

PMID- 29227360
TI  - The Importance of Specific Workplace Environment Characteristics for Maximum
      Health and Performance: Healthcare Workers' Perspective.
AB  - OBJECTIVE: To examine the importance of specific workplace environment
      characteristics for maximum health and performance, assigned by healthcare
      employees, and how they relate to the nature of their work. METHODS: A cross
      sectional mixed-method study was conducted with content analysis and robust
      regression models to examine the relationship between workplace environment
      characteristics and perceived importance in promoting health and performance.
      RESULTS: Our findings suggest that perceptions of key environment characteristics
      that safeguard health and performance in healthcare workplaces may vary by
      employee sex, setting, and nature of healthcare work involved. Theme and model
      descriptions of the influence of these factors on participant perceptions are
      provided. CONCLUSIONS: Employee feedback on workplace characteristics that impact
      health and performance could be instrumental in determining the priorities of
      workplace design.

PMID- 29227362
TI  - Comorbidity of Airway Inflammatory Diseases in Chemical and Building-Related
      Intolerance.
AB  - OBJECTIVES: This study investigated comorbidity in chemical intolerance (CI) and
      building- related intolerance (BRI) with (i) chronic sinusitis, chronic
      obstructive pulmonary disease, allergic and nonallergic asthma and allergic
      rhinitis, and (ii) airway inflammatory symptoms. METHODS: Data from two
      population-based questionnaire surveys, the Vasterbotten and Osterbotten
      Environmental Health Studies, were used. The participants were categorized as CI
      or BRI and referents, and binary logistic regression analysis was applied.
      RESULTS: Prevalence rates for the case groups were 7.2% to 40.0% for diseases and
      24.3% to 68.9% for symptoms, whereas adjusted odds ratios (ORs) were 3.4 to 26.1
      for diseases and 3.3 to 17.0 for symptoms, all being significantly higher than
      unity. Prevalence rates and ORs were in general higher in BRI than in CI.
      CONCLUSION: Inflammatory airway diseases and symptoms are associated with CI and
      BRI, which encourages further research regarding underlying mechanisms and
      treatments.

PMID- 29227361
TI  - Association Between Blood Pressure and Retinal Vessel Diameters Among Police
      Officers in the US Northeast.
AB  - OBJECTIVE: The aim of this study was to examine relationships of blood pressure
      with central retinal arteriolar equivalent (CRAE) and central retinal venular
      equivalent (CRVE) among 242 police officers. METHODS: Computerized retinal images
      of each eye were taken. Mean values of CRAE and CRVE were compared across
      hypertension status categories using analysis of variance and analysis of
      covariance. Associations of mean arterial blood pressure (MABP) with CRAE and
      CRVE were obtained using regression models. RESULTS: CRAE was significantly
      narrower in officers with uncontrolled hypertension (142.8 +/- 2.7 MUm), compared
      with those with controlled hypertension (153.6 +/- 2.7 MUm, P = 0.0013) and those
      with no hypertension (156.4 +/- 1.0 MUm, P <= 0.0001) after covariate adjustment.
      CRAE decreased by 3.43 MUm for each 5 mm Hg increase in MABP (P <= 0.0001).
      CONCLUSION: Uncontrolled hypertension was significantly associated with narrower
      retinal arterioles. No association was observed with retinal venules.

PMID- 29227363
TI  - Psychosocial Factors and Surgical Outcomes in Adult Spinal Deformity: Do Dementia
      Patients Have More Complications?
AB  - STUDY DESIGN: Retrospective analysis of a prospectively collected, national
      inpatient hospital database. OBJECTIVE: We aimed to investigate comorbid
      psychiatric disorders in the adult spinal deformity (ASD) population. We
      hypothesized that a high incidence of comorbid psychiatric disorders in ASD would
      negatively impact perioperative outcomes. SUMMARY OF BACKGROUND DATA: Patients
      with adult spinal fusion (ASF) suffer from severe back pain and often depression.
      Psychiatric comorbidities in the ASD population are not well understood, despite
      the apparent psychological effects of spinal deformity-related self-image.
      METHODS: The Nationwide Inpatient Sample databases from 2001 to 2009 were queried
      for patients ages 18 years or older with in-hospital stays including a spine
      arthrodesis. Patients were divided into two groups: ASD (diagnosis of scoliosis,
      excluding neuromuscular and congenital) and all other ASF. Subjects were further
      stratified by presence of a comorbid psychiatric diagnosis. Differences between
      each surgical group in psychiatric frequency and complications were calculated
      using analysis of variance, adjusted for operative complexity. A binary logistic
      regression analyzed the association between psychiatric diagnoses and likelihood
      of complications. RESULTS: A total of 3,366,352 ASF and 219,975 ASD patients were
      identified. The rate of comorbid psychiatric diagnoses in ASD was significantly
      higher (23.5%) compared to ASF patients (19.4%, P < 0.001). Complication rates
      were higher for ASD compared to ASF; patients without a psychiatric diagnosis had
      lower (or comparable) complication rates than psychiatric patients, across all
      disorder categories. Patients with psychotic disorders and dementia showed more
      complications than controls; patients with mood, anxiety and alcohol disorders
      showed fewer. CONCLUSION: Psychiatric comorbidities are more common in the ASD
      population than in adult fusion patients. ASD and ASF patients with the most
      common psychiatric disorders (mood, anxiety, and alcohol abuse) are not at
      increased risk for complications compared to controls. Those patients with
      psychotic disorders and dementia are at a significant risk for increased
      complications and surgeons should be aware of these specific risks. LEVEL OF
      EVIDENCE: 2.

PMID- 29227364
TI  - Posterolateral Diskectomies for Treatment of Pediatric Spinal Deformities.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: To investigate the indications,
      radiographic outcomes, and complications in children with spinal deformities
      treated with posterolateral diskectomy with posterior fusion (PLDF), and to
      compare them against those of patients treated with anteroposterior spinal fusion
      (APSF). SUMMARY OF BACKGROUND DATA: A novel technique for treating large, rigid
      spinal deformities in children has been proposed, consisting of PLDF at the apex
      of the deformity using an all-posterior approach. METHODS: We evaluated records
      of all patients 21 years or younger who underwent treatment for spinal deformity
      between 2010 and 2015 by one surgeon using PLDF (n = 56) or APSF (n = 21).
      RESULTS: The indications for PLDF were large, rigid curves (37 patients); focal
      curves with severe rotation (10 patients); or large curves with open triradiate
      cartilage (nine patients). PLDF patients had a mean (+/- standard deviation) of 3
      +/- 1 diskectomies and 14 +/- 3 posterior spinal levels fused. Compared with the
      APSF group, the PLDF group had significantly greater major curve correction (86%
      vs. 57%, P = 0.006), less blood transfused (mean, 2.5 +/- 2.6 vs. 4.0 +/- 3.3
      units, P = 0.038), and a lower rate of staged surgery (1.8% vs. 86%, P < 0.001).
      There were no significant differences between the PLDF and APSF groups in T1-S1
      length gained (mean, 6.2 +/- 3.4 vs. 6.6 +/- 8.8 cm, respectively; P = 0.77) or
      in the rate of major complications (P = 0.557). CONCLUSION: PLDF is an effective
      alternative to APSF for treating children with severe spinal deformities. It is
      effective for treating large, rigid curves with severe rotation and may be useful
      for treating large curves in children with open triradiate cartilage. LEVEL OF
      EVIDENCE: 4.

PMID- 29227365
TI  - Analysis of Successful Versus Failed Radiographic Outcomes After Cervical
      Deformity Surgery.
AB  - STUDY DESIGN: Prospective multicenter cohort study with consecutive enrollment.
      OBJECTIVE: To evaluate preoperative alignment and surgical factors associated
      with suboptimal early postoperative radiographic outcomes after surgery for
      cervical deformity. SUMMARY OF BACKGROUND DATA: Recent studies have demonstrated
      correlation between cervical sagittal alignment and patient-reported outcomes.
      Few studies have explored cervical deformity correction prospectively, and the
      factors that result in successful versus failed cervical alignment corrections
      remain unclear. METHODS: Patients with adult cervical deformity (ACD) included
      with either cervical kyphosis more than 10 degrees , C2-C7 sagittal vertical axis
      (cSVA) of more than 4 cm, or chin-brow vertical angle of more than 25 degrees .
      Patients were categorized into failed outcomes group if cSVA of more than 4 cm or
      T1 slope and cervical lordosis (TS-CL) of more than 20 degrees  at 6 months
      postoperatively. RESULTS: A total of 71 patients with ACD (mean age 62 yr, 56%
      women, 41% revisions) were included. Fourty-five had primary cervical deformities
      and 26 at the cervico-thoracic junction. Thirty-three (46.4%) had failed
      radiographic outcomes by cSVA and 46 (64.7%) by TS-CL. Failure to restore cSVA
      was associated with worse preoperative C2 pelvic tilt angle (CPT: 64.4 degrees 
      vs. 47.8 degrees , P = 0.01), worse postoperative C2 slope (35.0 degrees  vs.
      23.8 degrees , P = 0.004), TS-CL (35.2 degrees  vs. 24.9 degrees , P = 0.01), CPT
      (47.9 degrees  vs. 28.2 degrees , P < 0.001), "+" Schwab modifiers (P = 0.007),
      revision surgery (P = 0.05), and failure to address the secondary, thoracolumbar
      driver of the deformity (P = 0.02). Failure to correct TS-CL was associated with
      worse preoperative cervical kyphosis (10.4 degrees  vs. -2.1 degrees , P = 0.03),
      CPT (52.6 degrees  vs. 39.1 degrees , P = 0.04), worse postoperative C2 slope
      (30.2 degrees  vs. 13.3 degrees , P < 0.001), cervical lordosis (-3.6 degrees 
      vs. -15.1 degrees , P = 0.01), and CPT (37.7 degrees  vs. 24.0 degrees , P <
      0.001). Multivariate analysis revealed postoperative distal junctional kyphosis
      associated with suboptimal outcomes by cSVA (odds ratio 0.06, confidence interval
      0.01-0.4, P = 0.004) and TS-CL (odds ratio 0.15, confidence interval 0.02-0.97, P
      = 0.05). CONCLUSION: Factors associated with failure to correct the cSVA included
      revision surgery, worse preoperative CPT, and concurrent thoracolumbar deformity.
      Failure to correct the TS-CL mismatch was associated with worse preoperative
      cervical kyphosis and CPT. Occurrence of early postoperative distal junctional
      kyphosis significantly affects postoperative radiographic outcomes. LEVEL OF
      EVIDENCE: 3.

PMID- 29227366
TI  - Trends in Physician Reimbursement for Spinal Procedures Since 2010.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To identify trends in spinal
      procedure reimbursement in our practice since 2010. SUMMARY OF BACKGROUND DATA:
      In an uncertain healthcare climate with continuous reform, trends in physician
      reimbursement are unclear. Market forces of supply and demand, legislation
      imposing penalties for quality measures, local competition, and geographic
      location have the potential to affect reimbursement. An emphasis on quality-of
      care and cost reduction is placed on providers and insurers. In a high-cost area
      such as spine surgery, it is unknown what the reimbursement trends have been over
      the last 7 years of major healthcare reforms. METHODS: We collected payments
      received data for the 20 most commonly billed Current Procedural Terminology
      (CPT) codes for spinal surgery from January 2010 to December 2016. Payments were
      adjusted for inflation using the Consumer Price Index for Medical Care in the
      Northeastern United States. Insurers were separated into four groups: Medicare,
      Medicaid, Private Insurance, and Workers Compensation and No Fault (WC/NF). Using
      a weighted average to adjust for variation in procedures performed, average
      payments were trended over time. Average payments were trended by insurance group
      averaged by CPT code. RESULTS: After adjusting for inflation, average overall
      payments for spinal claims from 2010 to 2016 increased 13.6%. Average
      reimbursement declined 1.9% from 2010 to 2013 and rose 16.8% from 2014 to 2016.
      Average Medicaid payments increased 150.1% since 2010 whereas average Medicare
      payments rose 4.9%. Average reimbursement from private insurers and WC/NF claims
      decreased 16.2% and 8.5%, respectively, from 2010 to 2013; increasing 14.2% and
      12.5%, respectively, from 2014 to 2016. From 2010 to 2016, reimbursement for
      private insurance decreased 9.3% and increased 8.2% for WC/NF claims. CONCLUSION:
      Since 2010, inflation-adjusted reimbursement for spinal procedures increased in
      our practice. There was a decline from 2010 to 2013. Increases occurred from 2014
      to 2016 across all insurers. Medicaid payments more than doubled since 2010.
      LEVEL OF EVIDENCE: 3.

PMID- 29227367
TI  - Practice Patterns and Outcomes Associated With Early Sedation Depth in
      Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: Emerging data suggest that early deep sedation may negatively impact
      clinical outcomes. This systematic review and meta-analysis defines and
      quantifies the impact of deep sedation within 48 hours of initiation of
      mechanical ventilation, as described in the world's literature. The primary
      outcome was mortality. Secondary outcomes included hospital and ICU lengths of
      stay, mechanical ventilation duration, and delirium and tracheostomy frequency.
      DATA SOURCES: The following data sources were searched: MEDLINE, EMBASE, Scopus,
      Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews
      and Effects, Cochrane Database of Systematic Reviews databases,
      ClinicalTrials.gov, conference proceedings, and reference lists. STUDY SELECTION:
      Randomized controlled trials and nonrandomized studies were included. DATA
      EXTRACTION: Two reviewers independently screened abstracts of identified studies
      for eligibility. DATA SYNTHESIS: Nine studies (n = 4,521 patients) published
      between 2012 and 2017 were included. A random effects meta-analytic model
      revealed that early light sedation was associated with lower mortality (9.2%)
      versus deep sedation (27.6%) (odds ratio, 0.34 [0.21-0.54]). Light sedation was
      associated with fewer mechanical ventilation (mean difference, -2.1; 95% CI, -3.6
      to -0.5) and ICU days (mean difference, -3.0 (95% CI, -5.4 to -0.6). Delirium
      frequency was 28.7% in the light sedation group and 48.5% in the deep sedation
      group, odds ratio, 0.50 (0.22-1.16). CONCLUSIONS: Deep sedation in mechanically
      ventilated patients, as evaluated in a small number of qualifying heterogeneous
      randomized controlled trials and observational studies, was associated with
      increased mortality and lengths of stay. Interventions targeting early sedation
      depth assessment, starting in the emergency department and subsequent ICU
      admission, deserve further investigation and could improve outcome.

PMID- 29227368
TI  - Septic Cardiomyopathy.
AB  - OBJECTIVES: To describe, with an emphasis on clinical applications, what is known
      about the pathophysiology, management, and implications of septic cardiomyopathy
      in the adult ICU. DATA SOURCES AND STUDY SELECTION: A PubMed literature review
      was performed for relevant articles. Only articles in English that studied human
      adults with sepsis were included. DATA EXTRACTION AND DATA SYNTHESIS: Multiple
      competing definitions for septic cardiomyopathy hinder understanding of this
      entity. Although many patients with sepsis develop cardiac dysfunction, the
      impact of septic cardiomyopathy on prognosis and therapy remains to be
      demonstrated. Treatment of septic cardiomyopathy is aimed at treating the
      underlying sepsis and providing specific supportive care for cardiogenic shock
      when present. CONCLUSIONS: Septic cardiomyopathy is an important contributor to
      organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect
      patients' prognosis, especially when their cardiac index is substantially
      decreased. The implication of septic cardiomyopathy for both short- and long-term
      outcomes is an important area for future investigation.

PMID- 29227369
TI  - Ventilator-Free Day Outcomes Can Be Misleading.
AB  - INTRODUCTION: Acute respiratory distress syndrome often requires invasive
      mechanical ventilation, with both mortality and mechanical ventilation duration
      as outcomes of interest. The concept of ventilator-free days has been proposed as
      an outcome combining these two outcomes. Here we analyzed the construction of the
      ventilator-free day outcome and provided a hypothetical scenario to alert
      physicians that such an outcome can lead to misleading interpretations. METHODS:
      We proposed the isoventilator-free day curve concept and, using an analytical
      development, illustrated how a median ventilator-free day value can actually
      result from very different combinations of death rates and mechanical ventilation
      durations. We also used a hypothetical example to compare the Student t test,
      Wilcoxon rank-sum test, and Gray test (which accounts for death as a competing
      event with extubation) in comparing exposition to mechanical ventilation.
      RESULTS: A median ventilator-free day value of 10 days may mean that 10% of the
      patients died while survivors were ventilated during a median of 14 days or that
      40% died while survivors were ventilated during a median of 5 days. Changing the
      time horizon affected the Student t test but not the Wilcoxon rank-sum result.
      The Gray test was more relevant than both the Student t test and Wilcoxon rank
      sum test in identifying differences in groups showing highly different mechanical
      ventilation duration, despite equal median ventilator-free days. This approach
      was also illustrated using real data. CONCLUSIONS: Use of ventilator-free days as
      an outcome appears to have many drawbacks. Suitable methods of analyzing time to
      extubation should be preferred.

PMID- 29227370
TI  - C1-C2 Pedicle Screw Fixation for Pediatric Atlantoaxial Dislocation: Initial
      Results and Long-term Follow-up.
AB  - BACKGROUND: There are few studies reporting the use of atlantoaxial pedicle
      screws and the long-term effects of C1-C2 posterior fusion in children. Our study
      is to investigate the initial results of C1-C2 pedicle screw fixation for
      pediatric atlantoaxial dislocation (AAD) and assessed spontaneous change of
      postoperative radiography after a long-term follow-up period. METHODS: Posterior
      pedicle screw fixations were performed in 21 pediatric patients with AAD. All the
      patients underwent implant removal 1 year after their initial surgery and had
      regular follow-up with an average duration of 76.4 months (range, 52 to 117 mo).
      Clinical and radiographic data were then collected and compared. RESULTS: Frankel
      Grade was significantly improved at 3 months follow-up compared with pretreatment
      values. All patients had good bony fusion at a mean of 4.2+/-0.9 months (range, 3
      to 6 mo) after treatment. None of the patients experienced worsening neurological
      symptoms or injury to the vertebral artery. However, 2 cases experienced minor
      complications. Following removal of the implants, no spinal deformities or
      subaxial instabilities were found. The mean angle of sagittal curvature increased
      from 12.1+/-2.4 degrees (range, 0 to 22 degrees) immediately postoperatively to
      19.1+/-2.7 degrees (range, 6 to 31 degrees) at the final follow-up (P>0.05).
      CONCLUSIONS: The results demonstrated that C1-C2 pedicle screw fixation could
      achieve satisfactory initial results for the management of the pediatric AAD.
      Moreover, removal of the metal implant after bony fusion did not increase the
      risk of spinal deformity or subaxial instability at long-term follow-up.

PMID- 29227371
TI  - A Quality Improvement Initiative Reduces Cast Complications in a Pediatric
      Hospital.
AB  - BACKGROUND: Casts, while frequently used as routine treatment in pediatric
      orthopaedic practice, are not without complications. At our large tertiary care
      pediatric hospital, the baseline rate of all casting complications was 5.6
      complications per 1000 casts applied (0.56%). We tested the hypothesis that we
      could use quality improvement (QI) methodology to decrease the overall cast
      complication rate and improve patient care. METHODS: We initiated a QI program
      implementing concepts derived from the Institute for Healthcare Improvement
      models, including Plan-Do-Study-Act cycles, to decrease our cast complication
      rate. A resident casting education program was developed with a competency
      "checklist" to ensure that casts are applied, bivalved, and removed in a safe and
      standardized manner to prevent patient harm. AquaCast Saw Stop Protective Strips
      were required to be applied with every cast application. A review of our
      facility's processes and procedures determined adequate measures were in place to
      effectively manage inventory and maintenance of cast-saw blades. RESULTS: With
      the multimodal QI intervention, our cast complication rate was reduced to 1.61
      complications per 1000 applications, a >90% improvement. CONCLUSIONS:
      Implementation of QI concepts to perform a QI initiative resulted in a shift
      toward fewer cast complications, leading to overall improved patient care at a
      large tertiary pediatric hospital. LEVEL OF EVIDENCE: Level II-prospective cohort
      study.

PMID- 29227372
TI  - Osteofibrous Dysplasia of the Tibia in Children: Outcome Without Resection.
AB  - BACKGROUND: The proposed association between osteofibrous dysplasia and
      adamantinoma has led some to advocate resection of the entire lesion, which can
      require major subsequent reconstruction. However, this link remains unproven and
      there is some support in more recent literature for a less aggressive approach.
      This study aims to describe our experience managing pediatric tibial osteofibrous
      dysplasia with such an approach and to report functional outcomes in children
      treated thus. METHODS: A total of 28 cases of osteofibrous dysplasia in 25
      patients were managed at a referral center for pediatric bone tumors with
      observation in the first instance, then limited surgical intervention if required
      to address pain and deformity. Surgery aimed to restore stability and alignment
      without excising the lesion. Clinical records provided basic clinical outcome
      measures involving walking, recreation, orthoses and school/work participation
      and patients provided a Musculoskeletal Tumour Society score (MSTS) where
      contactable. RESULTS: Mean age at presentation was 6.0 years and mean follow-up
      was 8.3 years. Only 8 patients required surgery. According to basic outcome
      measures, 13 patients were symptom-free. About 15 patients (17 cases) provided a
      MSTS and the mean score was 24 of 30. No transformation to adamantinoma was
      observed. Those who presented at a younger age and with bilateral disease more
      often required surgery and remained symptomatic. CONCLUSIONS: A less aggressive
      approach to pediatric tibial osteofibrous dysplasia achieves good functional
      outcomes and patient satisfaction in most cases. Surgery is required in the
      minority of cases. Transformation to adamantinoma was not observed in this
      series. We recommend patient education, clinical observation and reactive
      intervention if required, rather than proactive resection and reconstruction.
      LEVEL OF EVIDENCE: Level IV-case series.

PMID- 29227373
TI  - Incidence of Meniscal Entrapment and Associated Knee Injuries in Tibial Spine
      Avulsions.
AB  - BACKGROUND: Tibial spine avulsions (TSA) have historically been treated as
      isolated injuries. Data on associated injuries are limited with existing
      literature reporting wide ranging incidences. The purpose of this multicenter
      study was to (1) describe the incidence of meniscal entrapment and associated
      knee injuries in TSA and to (2) compare surgical and magnetic resonance image
      (MRI) findings for these injuries. Our hypothesis is that tibial spine injuries
      are not usually isolated injuries, and other meniscal, ligament, and cartilage
      injuries may be present. METHODS: MRI and surgical reports for patients with a
      diagnosis of a tibial spine fracture were retrospectively reviewed. Type of
      fracture was recorded as noted in the reports along with concomitant meniscal
      entrapment and osteochondral, ligamentous, and meniscal injury. Images and
      reports were reviewed by an orthopaedic surgeon at each respective institution.
      RESULTS: A total of 163 patients were included in this study. MRI was done for 77
      patients and surgery was performed in 144 cases. Meniscal entrapment was found in
      39.9% of all patients. MRI diagnosed meniscus, osteochondral, and non-anterior
      cruciate ligament ligamentous injury was found in 31.2%, 68.8%, and 32.4% of
      cases, respectively. Surgically diagnosed meniscus, chondral, and non-anterior
      cruciate ligament ligamentous injury was found in 34.7%, 33.3%, and 5.6% of
      patients, respectively. CONCLUSIONS: TSA fractures are associated with
      significant risk for concomitant knee injuries including meniscal tear, bone
      contusion, and chondral injury. Incidence of meniscal entrapment found during
      surgery was high, in spite of low incidence of positive findings by MRI. LEVEL OF
      EVIDENCE: Level IV-retrospective case series.

PMID- 29227374
TI  - Collateral Ligament Knee Injuries in Pediatric and Adolescent Athletes.
AB  - BACKGROUND: The majority of research on medial (MCL) and lateral (LCL) collateral
      ligament injuries has focused on adults and combined collateral/cruciate
      injuries. The purpose of this study was to determine characteristics associated
      with isolated collateral ligament injuries in adolescents, and assess timing for
      return to sports. METHODS: Electronic medical records were queried to identify
      patients aged below 17 years who sustained a magnetic resonance imaging-confirmed
      isolated MCL or LCL injury over an 8-year period. Retrospective review then
      documented patient and injury characteristics and clinical course. General linear
      modeling was used to analyze risk factors for prolonged return to sports,
      continued pain or reinjury. RESULTS: Fifty-one knees (33 in males, 65%), mean age
      13.8 years (range, 5 to 17), were identified, of which 40 (78%) had MCL injuries.
      Over half (29, 57%) of knees had an open distal femoral physis including all 5
      bony avulsion injuries. Eleven (22%) had LCL injuries of which 3 (6%) had
      concurrent posterolateral corner injuries. Forty-two (82%) knees had injuries
      that occurred during sports. Eleven knees (28%) with MCL tears had a simultaneous
      patellar instability episode. Knee injuries that occurred during sports had 37%
      shorter recovery time (P=0.02). Eight knees (16%) experienced a reinjury and 12
      (24%) were followed over an extended period of time for various knee issues.
      Football injuries were more likely to be grade 3 (P=0.03), and football and
      soccer accounted for all grade III injuries. The mean return to sports was 2.2
      months, with grade III cases returning at 2.4 months, and 95% of cases within 4
      months. CONCLUSIONS: Isolated collateral ligament injuries are rare in adolescent
      athletes. MCL injuries, one-quarter of which occurred in conjunction with
      patellar instability events, were 4 times more common than LCL injuries, one
      quarter of which have other posterolateral corner structures involved. Grade III
      injuries represent 20% to 25% of collateral ligament injuries and occurred most
      commonly in football and soccer. LEVEL OF EVIDENCE: Level IV-retrospective case
      series.

PMID- 29227375
TI  - Impact of evacuation onstrends in the prevalence, treatment, and control of
      hypertension before and after a disaster.
AB  - OBJECTIVE: After the Great East Japan Earthquake in 2011, the prevalence of
      cardiovascular disease risk factors increased in victims. We examined the trends
      in the prevalence, treatment, and control of hypertension before and after the
      disaster, as well as the impact of evacuation. METHODS: Study participants were
      approximately 10 000 men and 12 000 women aged 40-74 years in each year from 2008
      to 2014. All of the participants had lived in radiation evacuation zones prior to
      the Fukushima nuclear crisis. The age-standardized prevalence, treatment, and
      control of hypertension were calculated using the direct method. In a comparison
      of evacuees with nonevacuees, the proportion ratios and 95% confidence intervals
      for hypertension, treatment, and control were calculated by Poisson regression
      with robust error variance adjusted for covariates in each year after the
      disaster. RESULTS: The age-standardized prevalence of hypertension peaked in 2012
      at 48.8% in men and 39.0% in women. By 2014, the treatment and control of
      hypertension had increased to 66.3 and 67.1% in men, and 70.6 and 68.1% in women,
      respectively. The multiadjusted proportion ratios for the prevalence, treatment,
      and control of hypertension in any given year were 1.02-1.03, 0.99-1.05, and 0.93
      1.06 in men, and 0.96-1.00, 0.99-1.05, and 1.06-1.11 in women, respectively.
      CONCLUSION: The prevalence of hypertension peaked 1 year after the disaster,
      while the treatment and control of hypertension increased thereafter. These
      results indicate that evacuation had little to no impact on the prevalence,
      treatment, and control of hypertension in the population of Fukushima Prefecture.

PMID- 29227376
TI  - Hypertensive heart disease beyond left ventricular hypertrophy: are we ready for
      echocardiographic strain evaluation in everyday clinical practice?
AB  - : Hypertension-induced left ventricular (LV) remodeling is a well known entity
      that has usually been studied with traditional echocardiographic techniques. In
      the last decade echocardiographic methods are focused on evaluation of heart
      mechanics. The strain assessment is considered as part of comprehensive
      echocardiographic examination. Nevertheless, LV strain and particularly
      longitudinal strain was proofed as a significant independent predictor of
      cardiovascular and total morbidity and mortality, stronger than LV ejection
      fraction. Considering the fact that hypertensive heart disease represents one of
      the most important risk factors for the development of heart failure with
      preserved ejection fraction, one should be careful and accurate in identifying
      subtle signs of cardiac dysfunction. The early detection of cardiac dysfunction
      by conventional echocardiographic methods is often not possible. The aim of the
      current article is to overview the main principles of LV mechanics and summarize
      the current knowledge and clinical significance of LV strain in hypertensive
      patients.

PMID- 29227377
TI  - Effectiveness of low-dose diuretics for blood pressure reduction to optimal
      values in prehypertension: a randomized clinical trial.
AB  - BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to
      achieve an optimal level of blood pressure (BP) in adults with prehypertension.
      METHODS: The PREVER-prevention trial was a randomized, parallel, double-blinded,
      placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic
      medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730
      volunteers with prehypertension who were aged 30-70 years, and who did not reach
      optimal blood pressure after 3 months of lifestyle intervention, were randomized
      to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo
      once a day. The main outcomes were the percentage of participants who achieved an
      optimal level of BP. RESULTS: A total of 372 participants were randomly allocated
      to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was
      noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05).
      The mean net reduction in SBP and DBP for the diuretic group compared with
      placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4),
      respectively. Most participants in the active treatment group (74.5%) and in the
      placebo group (80.7%) continued to have BP in the prehypertension range or
      progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the
      probability of individuals with prehypertension to achieve optimal BP but most of
      those treated continued to have a BP in the prehypertension range or progressed
      to having overt hypertension.

PMID- 29227379
TI  - NCF @ Work.

PMID- 29227378
TI  - Are You Weary?

PMID- 29227381
TI  - Etc.

PMID- 29227380
TI  - NCFI Your Global Connection.

PMID- 29227382
TI  - Forgiveness in the Workplace?

PMID- 29227383
TI  - The APRN as Servant Leader.

PMID- 29227384
TI  - Nursing in the Church.

PMID- 29227385
TI  - Student TXT.

PMID- 29227386
TI  - Point-Counterpoint: Exploring Ethical Dilemmas in Patient Care.

PMID- 29227387
TI  - Update: What Nurses Need to Know about Human Trafficking.
AB  - Nurses are key people who interact with victims of human trafficking in
      healthcare and other settings. This article provides a current overview of human
      trafficking, explains legal definitions, elements for protocols in healthcare
      settings when trafficking is suspected, nursing roles and responses, interview
      tools, resources, public health recommendations, and nursing education approaches
      to address human trafficking.

PMID- 29227388
TI  - 12 Hour Shifts: Literature Reviewed, Wise Use Challenged.
AB  - Concern is reported about the negative outcomes of 12-hour shifts for nurses,
      including sleep-deprived fatigue, negative neurobehavioral outcomes, and patient
      safety. However, 12-hour shifts remain the prevailing staffing method. When
      should the concern for nurses' health and well-being be factored into staffing
      decisions? If the 12-hour model was used more wisely, that is, nurses were not
      working too much and/or too long, would there be a need for change? Will nurses
      and researchers pursue ways to address the negative outcomes of 12-hour shifts?

PMID- 29227389
TI  - Learning Cultural Humility Through Stories and Global Service-Learning.
AB  - Service-learning experiences are utilized by nursing programs to increase
      cultural learning for students. Through storytelling, the concept of cultural
      humility can be explained to students preparing for upcoming intercultural
      experiences. This case study describes the experience of nursing students and
      educators on their first service-learning trip to Kenya, and how intercultural
      issues were navigated as students developed cultural humility. The story now is
      shared in preparation for subsequent international student nursing trips. The
      utilization of storytelling can be a model for others preparing for service
      learning experiences.

PMID- 29227390
TI  - Preparing Clinical Nurses for Nursing Research: Evaluation of Training Procedures
      in a Palliative Care Pilot Study.
AB  - The importance of academic nurse researchers partnering with clinical nurses for
      clinical research has been well articulated. A 4-hour training program designed
      to equip staff nurses to become fully engaged researchers in a palliative care
      end of life communication-focused research study resulted in enriched human
      caring skills and professional growth. Results indicate that the training
      (didactic lecture, group reflection, role-playing) was adequate to prepare the
      nurses to deliver the study protocol. Relevance for primary investigators,
      nurses, clinical institutions, those interested in partnered research, and
      professional growth are discussed.

PMID- 29227391
TI  - The Role of the Faith Community Nurse in Weight Management.
AB  - Over two thirds of U.S. adults are overweight or obese; many view long-term
      behavior change as unachievable. Faith community nurses are ideally positioned to
      help people learn strategies for successful weight management. This article
      discusses the role of faith in lifestyle modification, and the use of the 5 A's
      Model for weight management.

PMID- 29227392
TI  - Extending the Metaphor.

PMID- 29227393
TI  - Can Spiritual Care Be Coercive?

PMID- 29227394
TI  - Biblical Roots of First Aid.

PMID- 29227395
TI  - Mud Hut Learning.

PMID- 29227397
TI  - Chat Room.

PMID- 29227396
TI  - Mama's Here.

PMID- 29227398
TI  - PulseBeats.

PMID- 29227399
TI  - Reflections on Global Service Learning in India.
AB  - Global service learning is an action-oriented, pedagogical approach that engages
      students in the core values of academic excellence, social relevance, personal
      transformation, intentional diversity, and cultural competence. The experience of
      students and nurse educators who have participated in global service-learning
      trips to India is relayed, along with the healthcare system of several Indian
      states.

PMID- 29227400
TI  - Workplace Incivility in Nursing: A Literature Review Through the Lens of Ethics
      and Spirituality.
AB  - A literature review was conducted to evaluate existing knowledge of incivility in
      the nursing workplace through the lens of nursing ethics and spirituality. Study
      articles presented a consistent theme of improved organizational commitment and
      job satisfaction when spirituality was injected into the workplace. It seems
      plausible to suggest a positive correlation between spirituality and more civil
      environments in nursing workplaces.

PMID- 29227401
TI  - What Nurses Need to Know About Human Trafficking.

PMID- 29227402
TI  - The Role of the Faith Community Nurse in Weight Management.

PMID- 29227403
TI  - Reply.

PMID- 29227405
TI  - Osseous Convexity at the Anterior Fontanelle: A Presentation of Metopic Fusion?
AB  - BACKGROUND: Craniosynostosis, or a premature fusion of 1 or more cranial vault
      sutures, results in characteristic head shape deformities. In previous reports,
      an osseous prominence at the anterior fontanelle has been suggestive of adjacent
      suture fusion and local elevation in intracranial pressure (ICP). This prominence
      has been termed the "volcano" sign, and has been described in the anterior fusion
      of the sagittal suture and serves as an indication for surgery. METHODS: Two
      patients presented for head shape evaluation with mild metopic ridging and
      anterior fontanellar osseous convexities consistent with the volcano sign. Low
      dose computed tomography imaging was performed in both patients due to concern
      for underlying craniosynostosis with elevated locoregional ICP. RESULTS: In both
      patients, imaging was significant for a localized, superior forehead metopic
      fusion, as well as a bony, convex prominence at the site of the ossified anterior
      fontanelle. There were no other clinical or radiologic signs or symptoms to
      suggest elevated ICP. Surgery was not indicated in either patient. CONCLUSIONS:
      Here the authors present 2 patients with osseous convexities at the site of the
      closed anterior fontanelle without signs or symptoms of elevated ICP, or classic
      signs of metopic synostosis. The authors hypothesize that this pattern may be due
      to a form of mechanically induced premature fusion of a normal metopic suture
      that is focused superiorly at the bregma, with minimal resultant restriction of
      overall skull growth. This is in contrast to metopic synostosis, which primarily
      has a sutural pathology and leads to characteristic findings of hypotelorism and
      trigonocephaly.

PMID- 29227406
TI  - Unexpected Blooming Artifact in Brain Magnetic Resonance Imaging.
AB  - Unexpected foreign bodies are occasionally discovered during magnetic resonance
      imaging (MRI). These are often present unknown to the patient, missed during
      routine pre-MRI screening and result in unnecessary delay during MRI. The authors
      present a patient with traumatically embedded foreign body in the scalp that
      escaped pre-MRI screening and caused susceptibility artifacts during brain MRI.
      The object was surgically removed to allow the imaging to be completed. Patients
      with suspicion or history of facial trauma or with dental restorations are
      referred to concerned specialists for compatibility of hardware, restorations and
      for assessing risks during MRI due to these. This patient is presented as a
      reminder for clinicians to probe further during anamnesis and have a high index
      of suspicion for foreign bodies that may be present even after trivial injuries.

PMID- 29227407
TI  - A Three-Dimensional Anthropometric Evaluation of Facial Morphology.
AB  - OBJECTIVES: The aims of this study were to evaluate sexual dimorphism for facial
      features within Italian and Egyptian populations and to compare the facial
      morphology by sex between these 2 populations. MATERIALS AND METHODS: Three
      dimensional (3D) facial images were acquired by using the portable 3dMDface
      System, which captured 259 subjects from 2 population groups of Italian (n = 139)
      and Egyptian (n = 120). Each population was categorized into male and female
      groups for evaluation. All subjects in the groups were aged between 18 and 30
      years and had no apparent facial anomalies. A total of 23 anthropometric
      landmarks were identified on the 3D faces of each subject. The independent t test
      was used to analyze each data set obtained within each subgroup. RESULTS:
      Egyptian women tend to have distinct facial features when compared with Italian
      women; they had less prominent eyes, more nasal width, more height of upper and
      lower faces and more height of upper and lower vermilion lengths. Egyptian and
      Italian males demonstrated very close facial features. However, Egyptian males
      had more nasal width, length of alare, and mandibular height. CONCLUSIONS: Sexual
      dimorphism for facial features was presented in both the Italian and Egyptian
      populations. In addition, there were significant differences in facial morphology
      between these 2 populations, especially in females.

PMID- 29227408
TI  - The Hybrid Technical Management of Large and Complicated Traumatic Arteriovenous
      Fistula of Preauricular Region.
AB  - BACKGROUND: Arteriovenous fistula (AVF) is defined as an abnormal communication
      between the high flow arterial system and the low flow venous network, which
      directly connects the arterial feeding vessels and the near draining veins
      without normal intervening capillary bed. Arteriovenous fistula incurs in
      preauricular region is exceeding rare. Most of these fistulae occur as a result
      of an iatrogenic injury, the volume is small, feeding and draining vessels of
      feeding and draining are simple, and can be cured easily. However, the treatment
      of the large and complicated AVF after incidental trauma in preauricular region
      is a challenge even for senior neurosurgeon. In this study, the authors discuss
      the management of a traumatic AVF through combined therapeutic method of surgical
      ligation and transarterial embolization. It is fed by ipsilateral superficial
      temporal artery, internal maxillary artery, posterior auricular artery, and their
      accessory branches and is drained by ipsilateral common facial vein and external
      jugular vein. Also the etiology, clinical manifestations, pathology, diagnosis,
      and management are summarized. CONCLUSION: Large and complicated traumatic AVF in
      preauricular region is rare, often due from an injury in maxillofacial region,
      combined therapy needed.

PMID- 29227409
TI  - Differences in the Alignment Pattern of the Maxillary Dental Arch Following Fixed
      Orthodontic Treatment in Patients With Bilateral Cleft Lip and Palate:
      Anteroposterior-Collapsed Arch Versus Transverse-Collapsed Arch.
AB  - The purpose of this study was to investigate differences in the alignment pattern
      of the collapsed maxillary arch following fixed orthodontic treatment (FOT) in
      bilateral cleft lip and palate (BCLP) patients according to collapse type.
      Fifteen BCLP patients were divided into Group 1 (anteroposterior-collapsed arch,
      n = 7) and Group 2 (transverse-collapsed arch, n = 8) according to maxillary arch
      shape before FOT. Linear and angular variables of lateral cephalograms and dental
      models were evaluated before (T1) and after FOT (T2), and statistical analysis
      was performed. In cephalometric measurements at T1, both the groups exhibited
      retrusive maxillae, a Class III relationship, and lingual inclination of U1-SN.
      At T2, significant improvement of U1-SN was observed in both the groups (P < 0.01
      in Group 1; P < 0.05 in Group 2). In the model measurements at T1, the inter
      second premolar width (IP2W), inter-first molar width (IM1W), and left segmental
      angle were smaller in Group 2 than in Group 1 (IP2W, P < 0.001; IM1W, P < 0.05;
      LSA, P < 0.05). From T1 to T2, the arch width increased significantly in Group 2
      (inter-canine width, IP1W, IP2W, and IM1W; all P < 0.05), but not in Group 1.
      Therefore, there were significant differences in DeltaIP2W (2.4 mm versus 14.9
      mm, P < 0.01) and DeltaIM1W (-0.7 mm versus 5.9 mm, P < 0.001) between Groups 1
      and 2. In both the groups, the molar depth and right and left segmental angles
      increased significantly, while the premaxillary rotation angle decreased
      significantly (molar depth, RSA, LSA, and PMRA; all P < 0.05). The alignment
      strategy for the maxillary premolar and molar areas should be modified according
      to arch shape in BCLP patients.

PMID- 29227410
TI  - Recurrent Lower Eyelid Ectropion After Graft Surgery Using Autogenous Palmaris
      Longus Tendon.
AB  - A 78-year-old male experienced right lower eyelid ectropion following right
      facial trauma from a fall 5 years ago, for which he underwent autogenous palmaris
      longus tendon graft surgery at another clinic. Recurrence was noted 3 years after
      surgery. On first examination, there was outward turning of the lateral half of
      the right lower eyelid margin. We performed a lateral tarsal strip procedure with
      removal of the graft. Intraoperatively, the lateral part of the graft was located
      along the inferior tarsal border, whereas the medial part was located on the
      tarsal surface. The lateral stump had bifurcated; 1 branch had passed through a
      bony hole drilled at the base of the rim; and both branches had been ligated
      together on the rim surface. The medial side had been fixed to the medial canthal
      tendon. Postoperatively, the apposition of eyelid and ocular surface was good,
      and the patient experienced no recurrence after 1 year.

PMID- 29227411
TI  - Intraoral Pleomorphic Adenoma in Young Patients.
AB  - BACKGROUND: Intraoral pleomorphic adenoma (PA) is rare in young individuals, with
      only single clinical reports or small patient series reported previously. AIM:
      The aim of this study was to describe the clinicopathological features of PA in 4
      patients under 18 years of age, and to discuss the differential diagnosis of
      pediatric patients presenting with intraoral submucosal nodules. METHODS: Between
      2000 and 2015, all patients of intraoral PA in patients aged <=18 years diagnosed
      in the Oral Pathology Laboratory of the Universidade Federal de Pernambuco,
      Brazil, were retrieved for the study. Clinical data were recorded from the
      clinical charts. Histopathological slides stained with hematoxylin and eosin were
      reviewed to confirm the diagnosis. RESULTS: There were 4 cases of PA in patients
      aged <=18 years. All patients in this patient series were males, with a mean age
      of 16.7 years. Three cases occurred in the palate, and in 1 case, the upper lip
      was affected. All PAs appeared as a painless, smooth surface, well-circumscribed,
      and submucosal nodule. All patients were surgically excised and subsequent
      histopathological analysis revealed well-circumscribed tumors composed of cells
      that were arranged in ducts within a fibromyxoid stroma. No signs of recurrence
      were observed in 3 patients after a mean follow-up of 30 months. One patient is
      lost to follow-up. CONCLUSION: Although PAs are unusual in young patients, they
      should be considered in the differential diagnosis of oral submucosal nodules.

PMID- 29227412
TI  - Validity and Responsiveness to Change of the 30-Second Chair-Stand Test in Older
      Adults Admitted to an Emergency Department.
AB  - BACKGROUND AND PURPOSE: Few physical performance measurement tools are validated
      for acutely admitted older adults, and for this reason we aimed to examine the
      validity and responsiveness to change of the 30-second Chair-Stand Test (30s-CST)
      used to assess physical performance in older adults admitted to a short-stay unit
      in an emergency department. METHODS: Construct validity of the 30s-CST, using 8
      as a cutoff point for dependency in activities of daily living, was examined
      using 207 patients. Self-reported information on everyday activities was obtained
      by asking patients about need for help in bathing, dressing, cooking, cleaning,
      and shopping. Concurrent validity of the 30s-CST compared with the de Morton
      Mobility Index (DEMMI) on physical performance of acutely admitted older adults
      was examined with 156 patients. The analysis of concurrent validity included the
      entire DEMMI and 2 subsets of DEMMI: "DEMMI walking" and "DEMMI dynamic balance."
      The responsiveness to change in the 30s-CST compared with DEMMI was examined with
      117 patients. All patients were classified as having either low physical
      performance (30s-CST <=8) or high physical performance (30s-CST >8); these groups
      were used in the analysis of validity and responsiveness to change. RESULTS AND
      DISCUSSION: Regarding construct validity using 8 as a cutoff point, the study
      showed a significant difference between patients with low physical performance
      compared with patients with high physical performance. Moreover, a decrease in
      the 30s-CST was followed by an increase in the need for help with everyday
      activities. There was a significant association between the 30s-CST and DEMMI (r
      = 0.72); for every extra repetition in the 30s-CST, the DEMMI score increased by
      4.9. There was a significant association between the 30s-CST and the 2 subsets
      "DEMMI walking" and "DEMMI dynamic balance"; yet, a pronounced floor effect was
      found in the subsets. The analysis demonstrated a very wide prediction interval,
      indicating that DEMMI has a better responsiveness to change than the 30s-CST,
      especially in older adults with low physical performance. However, the 30s-CST is
      easier and faster to use than DEMMI. CONCLUSION: This study found a significant
      difference in the patients' need for help with everyday activities when comparing
      low and high physical performance groups. The concurrent validity of the 30s-CST
      was acceptable in assessing physical performance in older adults at the time of
      admission; the 30s-CST is thus a tool that is easy to use in older adults with
      acute disease. In contrast, based on very wide prediction intervals, DEMMI
      demonstrated better responsiveness to change than the 30s-CST, especially in
      older adults with low physical performance.

PMID- 29227413
TI  - The Association Between Body Adiposity Measures, Postural Balance, Fear of
      Falling, and Fall Risk in Older Community-Dwelling Women.
AB  - BACKGROUND AND PURPOSE: Recent investigations demonstrate an association between
      obesity and the propensity of older adults to fall. The aim of this study was to
      investigate the association between body adiposity measures, postural balance,
      fear of falling, and risk of falls in older women. METHODS: One hundred forty
      seven volunteers took part in this cross-sectional study. Participants underwent
      body composition assessment using dual-energy x-ray absorptiometry and had body
      mass index, waist circumference (WC), and body adiposity index measured. Postural
      balance was assessed using a force platform, while fear of falling and risk of
      falls were, respectively, evaluated by the Falls Efficacy Scale-International and
      the QuickScreen Clinical Falls Risk Assessment. RESULTS AND DISCUSSION: All
      adiposity measures were correlated to at least 1 postural stability parameter and
      to fear of falling (rho= 0.163, P < .05 to r = 0.337, P < .001); however, WC was
      the index most strongly correlated to risk of falls (rho= 0.325; P < .001). When
      obesity was classified using WC, it was observed that compared with nonobese
      individuals (n = 51), obese individuals (n = 96) exhibited greater center of
      pressure displacement in the anteroposterior and mediolateral axes, especially
      during conditions with feet apart (P < .05). The obese group also exhibited an
      increased fear of falling (28.04 vs 24.59; P = .002) and had a higher proportion
      of individuals with increased fall risk (72% vs 35%; P < .001). CONCLUSION: In
      summary, adiposity measures are associated with risk of falls in older women,
      which might be mediated by reduced postural balance and increased fear of
      falling. Among these indices, WC, an easy and low-cost assessment, demonstrated
      the strongest association with falls-related outcomes.

PMID- 29227414
TI  - The diagnostic process of stable angina: still many doubts since Heberden's first
      description 250 years ago.
AB  - : Since Heberden's first description, stable angina has represented a challenge
      for the clinicians. Even the most recent guidelines seem ineffective to correctly
      identify patients who should be sent to cath labs. Still too many patients who
      undergo coronary angiography are found not to have significant lesions; moreover,
      its extensive use as the first diagnostic test leads to revascularizations with
      uncertain appropriateness and prognostic significance. These considerations
      underline the importance of noninvasive testing before sending patients to
      invasive coronary angiography. However, it is still debatable whether it is
      better to pursue anatomic evaluation of the coronary tree with the use of
      computed tomography or assessment of myocardial ischemia, a controversy which has
      not been resolved by recent trials comparing the two diagnostic modalities. A
      combined approach using both functional and anatomic testing may lead to a more
      careful risk stratification before invasive coronary angiography. The aim of this
      article is to discuss the most recent evidence in this field, and its application
      in clinical practice.

PMID- 29227415
TI  - Development of a Survey to Assess Local Health Department Organizational
      Processes and Infrastructure for Supporting Obesity Prevention.
AB  - Local health departments (LHDs) have an important function in controlling the
      growing epidemic of obesity in the United States. Data are needed to gain insight
      into the existence of routine functions and structures of LHDs that support and
      sustain obesity prevention efforts. The purpose of this study was to develop and
      examine the reliability of measures to assess foundational LHD organizational
      processes and functions specific to obesity prevention. Survey measures were
      developed using a stratified, random sample of US LHDs to assess supportive
      organizational processes and infrastructure for obesity prevention representing
      different domains. Data were analyzed using weighted kappa and intraclass
      correlation coefficient for assessing test-retest reliability. Most items and
      summary indices in the majority of survey domains had moderate/substantial or
      almost perfect reliability. The overall findings support this survey instrument
      to be a reliable measurement tool for a large number of processes and functions
      that comprise obesity prevention-related capacity in LHDs.

PMID- 29227416
TI  - Rurality, Quality Improvement Maturity, and Accreditation Readiness: A Comparison
      Study of Colorado, Kansas, and Nebraska Local Health Departments.
AB  - OBJECTIVE: To compare local health department (LHD) accreditation readiness (AR)
      and quality improvement (QI) maturity in 3 states, between LHDs with varying
      levels of rurality, and across an LHD staffing-level continuum. DESIGN: This was
      a cross-sectional comparative study that included an online survey administered
      to LHD directors in Colorado, Kansas, and Nebraska. The survey included 10
      questions assessed on a 5-point Likert scale covering 3 QI domains and 13
      questions covering 5 AR domains. The median score for both QI maturity and AR was
      calculated by each state, by the number of full-time equivalent staff employed at
      the LHD, and by a measure of rurality and population density. SETTING AND
      PARTICIPANTS: A total of 156 LHDs from the states of Colorado, Kansas, and
      Nebraska. MAIN OUTCOME MEASURE(S): QI maturity and AR scores. RESULTS: A majority
      (59%) of the surveyed LHDs plan to apply or have already applied for Public
      Health Accreditation Board (PHAB) accreditation. The overall QI maturity and AR
      scores were highest in Nebraska, as was the intent to seek PHAB accreditation and
      current use of PHAB standards. Across levels of rurality and staffing, LHD QI
      maturity scores were similar; however, AR scores improved as LHD staffing levels
      increased and rurality decreased. CONCLUSIONS: Small LHDs and rural LHDs have QI
      maturity levels that are comparable to larger, less rural LHDs, but their AR is
      much lower. As accreditation has been found to have positive benefits, it is
      important that all LHDs have the capacity and resources to meet the performance
      standards required of accredited LHDs. Small, rural LHDs may need additional
      resources and support in order to improve their ability to be accredited and/or
      certain accreditation requirements may need modification to make accreditation
      more accessible to small LHDs.

PMID- 29227417
TI  - Cost Analysis of Prevention Research Centers: Instrument Development.
AB  - The 2014-2019 Prevention Research Centers (PRC) Program Funding Opportunity
      Announcement stated that "all applicants will be expected to collaborate with CDC
      to collect data to be able to perform cost analysis." For the first time in the
      30-year history of the PRC Program, a cost indicator was included in the PRC
      Program Evaluation and a cost analysis (CA) instrument developed. The PRC-CA
      instrument systematically collects data on the cost of the PRC core research
      project to eventually answer the CDC PRC Program Evaluation question: "To what
      extent do investments in PRCs support the scalability, sustainability, and
      effectiveness of the outcomes resulting from community-engaged efforts to improve
      public health?" The objective of this article is to briefly describe the
      development of the PRC-CA instrument. Data obtained from the PRC-CA instrument
      can be used to generate cost summaries to inform decision making within the PRC
      Program and each individual PRC.

PMID- 29227418
TI  - Development and Validation of Surveillance-Based Algorithms to Estimate Hepatitis
      C Treatment and Cure in New York City.
AB  - CONTEXT: Treatment options for chronic hepatitis C virus (HCV) have improved in
      recent years. The burden of HCV in New York City (NYC) is high. Measuring
      treatment and cure among NYC residents with HCV infection will allow the NYC
      Department of Health and Mental Hygiene (DOHMH) to appropriately plan
      interventions, allocate resources, and identify disparities to combat the
      hepatitis C epidemic in NYC. OBJECTIVE: To validate algorithms designed to
      estimate treatment and cure of HCV using RNA test results reported through
      routine surveillance. DESIGN: Investigation by NYC DOHMH to determine the true
      treatment and cure status of HCV-infected individuals using chart review and HCV
      test data. Treatment and cure status as determined by investigation are compared
      with the status determined by the algorithms. SETTING: New York City health care
      facilities. PARTICIPANTS: A total of 250 individuals with HCV reported to the New
      York City Department of Health and Mental Hygiene (NYC DOHMH) prior to March 2016
      randomly selected from 15 health care facilities. MAIN OUTCOME MEASURES: The
      sensitivity and specificity of the algorithms. RESULTS: Of 235 individuals
      successfully investigated, 161 (69%) initiated treatment and 96 (41%) achieved
      cure since the beginning of 2014. The treatment algorithm had a sensitivity of
      93.2% (95% confidence interval [CI], 89.2%-97.1%) and a specificity of 83.8% (95%
      CI, 75.3%-92.2%). The cure algorithm had a sensitivity of 93.8% (95% CI, 88.9%
      98.6%) and a specificity of 89.4% (95% CI, 83.5%-95.4%). Applying the algorithms
      to 68 088 individuals with HCV reported to DOHMH between July 1, 2014, and
      December 31, 2016, 28 392 (41.7%) received treatment and 16 921 (24.9%) were
      cured. CONCLUSIONS: The algorithms developed by DOHMH are able to accurately
      identify HCV treatment and cure using only routinely reported surveillance data.
      Such algorithms can be used to measure treatment and cure jurisdiction-wide and
      will be vital for monitoring and addressing HCV. NYC DOHMH will apply these
      algorithms to surveillance data to monitor treatment and cure rates at city-wide
      and programmatic levels, and use the algorithms to measure progress towards
      defined treatment and cure targets for the city.

PMID- 29227419
TI  - Lessons Learned From the Environmental Public Health Tracking Sub-County Data
      Pilot Project.
AB  - OBJECTIVE: Small area data are key to better understanding the complex
      relationships between environmental health, health outcomes, and risk factors at
      a local level. In 2014, the Centers for Disease Control and Prevention's National
      Environmental Public Health Tracking Program (Tracking Program) conducted the Sub
      County Data Pilot Project with grantees to consider integration of sub-county
      data into the National Environmental Public Health Tracking Network (Tracking
      Network). DESIGN: The Tracking Program and grantees developed sub-county-level
      data for several data sets during this pilot project, working to standardize
      processes for submitting data and creating required geographies. Grantees
      documented challenges they encountered during the pilot project and documented
      decisions. RESULTS: This article covers the challenges revealed during the
      project. It includes insights into geocoding, aggregation, population estimates,
      and data stability and provides recommendations for moving forward. CONCLUSION:
      National standards for generating, analyzing, and sharing sub-county data should
      be established to build a system of sub-county data that allow for comparison of
      outcomes, geographies, and time. Increasing the availability and accessibility of
      small area data will not only enhance the Tracking Network's capabilities but
      also contribute to an improved understanding of environmental health and informed
      decision making at a local level.

PMID- 29227420
TI  - US State Public Health Departments Special Pathogen Planning.
AB  - CONTEXT: US state public health departments played key roles in planning for and
      responding to confirmed and suspected cases of Ebola virus disease (EVD) during
      the 2014-2016 outbreak, including designating select hospitals as high-level
      isolation units (HLIUs) for EVD treatment in conjunction with the Centers for
      Disease Control and Prevention. OBJECTIVE: To identify existing guidelines and
      perspectives of state health departments pertaining to the management and
      transport of patients with EVD and other highly hazardous communicable diseases
      (HHCDs). DESIGN: An electronic 8-question survey with subquestions was
      administered as a fillable PDF. SETTING: The survey was distributed to publicly
      accessible e-mails of state health department employees. PARTICIPANTS: State
      epidemiologists, emergency preparedness directors, or chief medical officers from
      each of the 50 states and the District of Columbia were contacted; a
      representative from 36 states and the District of Columbia responded (73%). MAIN
      OUTCOME MEASURES: Descriptive statistics were used to identify the proportion of
      state health departments with various existing protocols. RESULTS: A majority of
      states reported that they would prefer patients confirmed with viral hemorrhagic
      fevers (eg, EVD, Marburg fever) and smallpox be transported to an HLIU for
      treatment rather than remain at the initial hospital of diagnosis. While most
      (89%) states had written guidelines for the safe transportation of patients with
      HHCDs, only 6 (16%) had written protocols for the management of accidents or
      other travel disruptions that may occur during HHCD transport within the state.
      Twenty-two state health departments (59%) had operationally exercised transport
      of a patient to an HLIU. CONCLUSIONS: Nearly half of states in the United States
      lack an HLIU, yet most prefer to have patients with HHCDs treated in high-level
      isolation. Recent budget cuts and uncertainty of future funding threaten the
      abilities of health departments to devote the necessary resources and staff to
      prepare for and deliver the desired care to HHCD cases. The lack of HLIUs in some
      states may complicate transport to a geographically proximate HLIU. Moreover,
      limited guidance on diseases that warrant high-level isolation may cause
      disagreement in HHCD patient placement between health departments, diagnosing
      facilities, and HLIUs.

PMID- 29227421
TI  - An Assessment of Information Exchange Practices, Challenges, and Opportunities to
      Support US Disease Surveillance in 3 States.
AB  - BACKGROUND: State and local public health agencies collect and use surveillance
      data to identify outbreaks, track cases, investigate causes, and implement
      measures to protect the public's health through various surveillance systems and
      data exchange practices. PURPOSE: The purpose of this assessment was to better
      understand current practices at state and local public health agencies for
      collecting, managing, processing, reporting, and exchanging notifiable disease
      surveillance information. METHODS: Over an 18-month period (January 2014-June
      2015), we evaluated the process of data exchange between surveillance systems,
      reporting burdens, and challenges within 3 states (California, Idaho, and
      Massachusetts) that were using 3 different reporting systems. RESULTS: All 3
      states use a combination of paper-based and electronic information systems for
      managing and exchanging data on reportable conditions within the state. The flow
      of data from local jurisdictions to the state health departments varies
      considerably. When state and local information systems are not interoperable,
      manual duplicative data entry and other work-arounds are often required. The
      results of the assessment show the complexity of disease reporting at the state
      and local levels and the multiple systems, processes, and resources engaged in
      preparing, processing, and transmitting data that limit interoperability and
      decrease efficiency. CONCLUSIONS: Through this structured assessment, the Centers
      for Disease Control and Prevention (CDC) has a better understanding of the
      complexities for surveillance of using commercial off-the-shelf data systems
      (California and Massachusetts), and CDC-developed National Electronic Disease
      Surveillance System Base System. More efficient data exchange and use of data
      will help facilitate interoperability between National Notifiable Diseases
      Surveillance Systems.

PMID- 29227422
TI  - Assessment of the Sustainability Capacity of a Coordinated Approach to Chronic
      Disease Prevention.
AB  - OBJECTIVE: This article outlines some factors that influenced the sustainability
      capacity of a coordinated approach to chronic disease prevention in state and
      territory health departments. DESIGN: This study involved a cross-sectional
      design and mixed-methods approach. Quantitative data were collected using the
      Program Sustainability Assessment Tool (PSAT), a 40-item multiple-choice
      instrument that assesses 8 domains of sustainability capacity (environmental
      support, funding stability, partnerships, organizational capacity, program
      evaluation, program adaptation, communications, and strategic planning).
      Qualitative data were collected via phone interviews. PARTICIPANTS: The PSAT was
      administered to staff and stakeholders from public health departments in 50 US
      states, District of Columbia, and Puerto Rico, who were involved in the
      implementation of coordinated chronic disease programs. Phone interviews were
      conducted with program coordinators in each state. MAIN OUTCOME MEASURE(S):
      Sustainability score patterns and state-level categorical results, as well as
      strengths and opportunities for improvement across the 8 program sustainability
      domains, were explored. RESULTS: On average, programs reported the strongest
      sustainability capacity in the domains of program adaptation, environmental
      support, and organizational capacity, while funding stability, strategic
      planning, and communications yielded lowest scores, indicating weakest capacity.
      Scores varied the most by state in environmental support and strategic planning.
      CONCLUSION: The PSAT results highlight the process through which states
      approached the sustainability of coordinated chronic disease initiatives. This
      process included an initial focus on program evaluation and partnerships with
      transfer of priority to long-term strategic planning, communications, and funding
      stability to further establish coordinated chronic disease efforts. Qualitative
      interviews provided further context to PSAT results, indicating that leadership,
      communications, partnerships, funding stability, and policy change were perceived
      as keys to success of the transition. Integrating these findings into future
      efforts may help those in transition establish greater sustainability capacity.
      The PSAT results and interviews provide insight into the capacity for
      sustainability for programs transitioning from traditional siloed programs to
      coordinated chronic disease programs.

PMID- 29227423
TI  - Evaluating the Potential Health and Revenue Outcomes of a 100% Healthy Vending
      Machine Nutrition Policy at a Large Agency in Los Angeles County, 2013-2015.
AB  - CONTEXT: Healthy vending machine policies are viewed as a promising strategy for
      combating the growing obesity epidemic in the United States. Few studies have
      evaluated the short- and intermediate-term outcomes of healthy vending policies,
      especially for interventions that require 100% healthy products to be stocked.
      OBJECTIVE: To evaluate the potential impact of a 100% healthy vending machine
      nutrition policy. DESIGN: The vendor's quarterly revenue, product sales records,
      and nutritional information data from 359 unique vending machines were used to
      conduct a baseline and follow-up policy analysis. SETTING: County of Los Angeles
      facilities, 2013-2015. PARTICIPANTS: Vending machines in facilities located
      across Los Angeles County. INTERVENTION: A healthy vending machine policy
      executed in 2013 that required 100% of all products sold in contracted machines
      meet specified nutrition standards. OUTCOME MEASURES: Policy adherence; average
      number of calories, sugar, and sodium in food products sold; revenue change.
      RESULTS: Policy adherence increased for snacks and beverages sold by the vending
      machines by 89% and 98%, respectively. Average snack and beverage revenues
      decreased by 37% and 34%, respectively, during the sampled period. CONCLUSIONS:
      Although a 100% healthy vending policy represents a promising strategy for
      encouraging purchases of healthier foods, steps should be taken to counteract
      potential revenue changes when planning its implementation.

PMID- 29227424
TI  - Effect of Antiretroviral Therapy on Growth Parameters of Children With HIV
      Infection.
AB  - BACKGROUND: Children living with HIV (CLHIV) commonly experience growth failure.
      We report growth parameters in CLHIV at baseline and during 3 years of
      antiretroviral therapy (ART). METHODS: Records of CLHIV who had completed at
      least 3 years on ART were reviewed after excluding subjects who died, were lost
      to follow-up or developed treatment failure to assess impact of sustained
      administration of ART. Height-for-age (HFA) and body mass index for age (BFA) Z
      scores were calculated, and proportion of CLHIV with wasting and stunting
      estimated at baseline, 6, 12, 24 and 36 months after starting ART using the
      linear mixed model. Factors influencing significant changes in growth parameters
      were assessed. RESULTS: HFA Z score improved steadily from -3.12 at baseline to 
      2.33 at 36 months of ART. The prevalence of stunting declined from 77.7% to 59.2%
      during this period. BFA Z scores improved from -1.2 at baseline to -0.4 at12
      months on ART but declined to -1.0 at 36 months. The proportion of subjects with
      wasting was 29.3%, 9.7% and 16.7% at baseline, 12 and 36 months, respectively.
      Baseline clinical stage (1 + 2), absence of wasting and lower HFA Z score had
      significant positive influence on changes in HFA Z score, while younger age at
      ART initiation and a low baseline BFA Z score had a positive influence on catch
      up in body mass index. Including data of children who died or developed treatment
      failure did not impact upon the results. CONCLUSION: Majority of CLHIV are
      stunted at the start of ART. ART was only partially effective in countering
      malnutrition and growth failure in CLHIV.

PMID- 29227425
TI  - Editor's Commentary: Vaccines as a Tool to Combat Antibiotic Resistance.

PMID- 29227426
TI  - Mycobacterial Disease in Immunocompromised Children in a High Endemic Area.

PMID- 29227427
TI  - Is Late-onset Gram-negative Bloodstream Infection Associated with
      Gastrointestinal Pathology in Infants Hospitalized in Neonatal Units?

PMID- 29227428
TI  - Asymmetric Oligoarthritis With Enthesitis Associated With Acute Mumps Virus
      Infection.

PMID- 29227429
TI  - Looking Back to Move Forward: Editorial by New Editor-in-Chief Simon Kitto.

PMID- 29227430
TI  - Continuing Education Meets the Learning Organization: The Challenge of a Systems
      Approach to Patient Safety.
AB  - Since the release of the report of the Institute of Medicine on medical errors
      and patient safety in November 1999, health policy makers and health care leaders
      in several nations have sought solutions that will improve the safety of health
      care. This attention to patient safety has highlighted the importance of a
      learning approach and a systems approach to quality measurement and improvement.
      Balanced with the need for public disclosure of performance, confidential
      reporting with feedback is one of the prime ways that nations such as the United
      States, Canada, the United Kingdom, and Australia have approached this challenge.
      In the United States, the Quality Interagency Coordination Task Force has
      convened federal agencies that are involved in health care quality improvement
      for a coordinated initiative. Based on an investment in a strong research
      foundation in health care quality measurement and improvement, there are eight
      key lessons for continuing education if it is to parlay the interest in patient
      safety into enhanced continuing education and quality improvement in learning
      health care systems. The themes for these lessons are (1) informatics for
      information, (2) guidelines as learning tools, (3) learning from opinion leaders,
      (4) learning from the patient, (5) decision support systems, (6) the team
      learning together, (7) learning organizations, and (8) just-in-time and point-of
      care delivery.

PMID- 29227431
TI  - Faculty Development for Continuing Interprofessional Education and Collaborative
      Practice.
AB  - This article proposes a framework for faculty development in continuing
      interprofessional education (CIPE) and collaborative practice. The framework is
      built on best practices in faculty development and CIPE. It was informed by local
      experience in the development, delivery, and evaluation of a faculty development
      program to promote capacity for dissemination of concepts relating to
      interprofessional education (IPE) and interprofessional collaboration (IPC) in
      health care environments. Interprofessional education has been demonstrated in
      clinical contexts to enhance interprofessional collaboration, patient care, and
      health outcomes. With curriculum design, teaching methods, and educational
      strategies in faculty development, it is possible to enhance the impact of IPE in
      clinical contexts. Faculty development activities themselves can model effective
      interprofessional education methods and practice. An IPE curriculum and teaching
      and education strategies are outlined. Strategic planning, including the
      application of a systems approach, attention to the principles of effective
      learning, and an outcomes-based curriculum design are recommended for the
      development of continuing IPE faculty development programs that enhance
      interprofessional collaboration.

PMID- 29227432
TI  - CPD and KT: Models Used and Opportunities for Synergy.
AB  - The two fields of continuing professional development (CPD) and knowledge
      translation (KT) within the health care sector, and their related research have
      developed as somewhat parallel paths with limited points of overlap or
      intersection. This is slowly beginning to change. The purpose of this paper is to
      describe and compare the dominant conceptual models informing each field with the
      view of increasing understanding and appreciation of the two fields, how they are
      similar and where they differ, and the current and potential points of
      intersection. The models include the "knowledge-to-action" (KTA) cycle informing
      KT, models informing CPD curriculum design and individual self-directed learning,
      and the Kirkpatrick model for evaluating educational outcomes. When compared
      through the perspectives of conceptual designs, processes, and outcomes, the
      models overlap. We also identify shared gaps in both fields (eg, the need to
      explore the influence of the context in which CPD and KT interventions take
      place) and suggest opportunities for synergies and for moving forward.

PMID- 29227433
TI  - Integrating Essential Components of Quality Improvement into a New Paradigm for
      Continuing Education.
AB  - Continuing education (CE) that strives to improve patient care in a complex
      health care system requires a different paradigm than CE that seeks to improve
      clinician knowledge and competence in an educational setting. A new paradigm for
      CE is necessary in order to change clinician behavior and to improve patient
      outcomes in an increasingly patient-centered, quality-oriented care context. The
      authors assert that a new paradigm should focus attention on an expanded and
      prioritized list of educational outcomes, starting with those that directly
      affect patients. Other important components of the paradigm should provide
      educational leaders with guidance about what interventions work, reasons why
      interventions work, and what contextual factors may influence the impact of
      interventions. Once fully developed, a new paradigm will be helpful to educators
      in designing and implementing more effective CE, an essential component of
      quality improvement efforts, and in supporting policy trends and in promoting CE
      scholarship. The purpose of this article is to rekindle interest in CE theory and
      to suggest key components of a new paradigm.

PMID- 29227434
TI  - Evaluations of Educational Interventions: Getting Them Published and Increasing
      Their Impact.

PMID- 29227435
TI  - Appreciation of JCEHP Editor-In-Chief Emeritus, Curtis A. Olson, PhD, 2010 to
      2017.

PMID- 29227436
TI  - The Effect of Acetaminophen on Temperature in Critically Ill Children: A
      Retrospective Analysis of Over 50,000 Doses.
AB  - OBJECTIVES: Acetaminophen is widely used in PICUs. Although randomized controlled
      trials suggest that acetaminophen significantly reduces body temperature in
      adults, the effect of acetaminophen on temperature in critically ill children has
      not been previously quantified. DESIGN: Retrospective observational cohort study.
      SETTING: Single-center general and cardiac PICU in a specialist children's
      hospital. PATIENTS: All children who received acetaminophen or had a fever
      (temperature >= 38 degrees C) while on the ICU over a 40-month period (September
      2012 to December 2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In
      total, 58,177 doses of acetaminophen were administered, with temperature data
      available for analysis for 54,084 doses. Temperature decreased by 0.11 degrees C
      (95% CI, 0.09-0.14 degrees C) 4 hours post acetaminophen dose, after adjustment
      for weight and illness severity. In children who had a fever and were given
      acetaminophen, temperature decreased by 0.78 degrees C (95% CI, 0.74-0.82 degrees
      C). Temperature decreased by 0.88 degrees C (95% CI, 0.85-0.92 degrees C) in
      children who had fever but did not receive acetaminophen. The change in
      temperature associated with fever was significantly different between those who
      did and did not receive acetaminophen (likelihood ratio statistic 246.06; p < 2.2
      * 10). CONCLUSIONS: Acetaminophen is associated with a significant decrease in
      temperature in children with fever. However, temperature may decrease following
      fever without acetaminophen in the PICU. The threshold to use acetaminophen must
      be understood to determine the true effect on temperature in any future trials.

PMID- 29227437
TI  - Reducing Childhood Admissions to the PICU for Poisoning (ReCAP2) by Predicting
      Unnecessary PICU Admissions After Acute Intoxication.
AB  - OBJECTIVE: To derive and validate clinical prediction models to identify children
      at low risk of clinically significant intoxications for whom intensive care
      admission is unnecessary. DESIGN: Retrospective review of data in the National
      Poison Data Systems from 2011 to 2014 and Georgia Poison Center cases from July
      to December 2016. SETTING: United States PICUs and poison centers participating
      in the American Association of Poison Control Centers from 2011 to 2016.
      PATIENTS: Children 18 years and younger admitted to a United States PICU
      following an acute intoxication. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The primary study outcome was the occurrence of clinically significant
      intoxications defined a priori as organ system-based clinical effects that
      require intensive care monitoring and interventions. We analyzed 70,364 cases.
      Derivation (n = 42,240; 60%) and validation cohorts (n = 28,124; 40%) were
      randomly selected from the eligible population and had similar distributions of
      clinical effects and PICU interventions. PICU interventions were performed in
      1,835 children (14.1%) younger than 6 years, in 374 children (15.4%) 6-12 years,
      and in 4,446 children (16.5%) 13 years and older. We developed highly predictive
      models with an area under the receiver operating characteristic curve of 0.834 (<
      6 yr), 0.771 (6-12 yr), and 0.786 (>=13 yr), respectively. For predicted
      probabilities of less than or equal to 0.10 in the validation cohorts, the
      negative predictive values were 95.4% (< 6 yr), 94.9% (6-12 yr), and 95.1% (>= 13
      yr). An additional 700 patients from the Georgia Poison Center were used to
      validate the model and would have reduced PICU admission by 31.4% (n = 110).
      CONCLUSIONS: These validated models identified children at very low risk of
      clinically significant intoxications for whom pediatric intensive care admission
      can be avoided. Application of this model using Georgia Poison Center data could
      have resulted in a 30% reduction in PICU admissions following intoxication.

PMID- 29227438
TI  - Transcanal Transpromontorial Acoustic Neuroma Surgery: Results and Facial Nerve
      Outcomes.
AB  - BACKGROUND: Recently, the transcanal approach for the removal of acoustic
      neuromas has been introduced. Facial nerve (FN) preservation is one of the main
      challenges of this kind of surgery. OBJECTIVE: To describe our experience in the
      surgical treatment of acoustic neuromas, focusing on the functional results of FN
      preservation after a transcanal approach. METHODS: A retrospective chart review
      was carried out on clinical data and videos from operations on 49 patients who
      underwent surgery with a totally transcanal exclusive endoscopic approach for
      Koos stage I-II lesions, or an enlarged transcanal transpromontorial approach for
      Koos stage II-III tumors, between March 2012 and February 2017. Patients and
      tumor characteristics, clinical manifestations, radiologic features, audiological
      results, FN outcomes (according to the House-Brackmann [HB] grading system) and
      complications were evaluated. Tumors were classified according to the Koos
      grading system. RESULTS: The age of the patients (34 females and 15 males) ranged
      from 27 to 77 years (mean age: 54.9 yr). Preoperative diagnosis was "vestibular
      schwannoma" in all patients. At the last follow-up (range 1-60 mo, mean 13.9 mo),
      42 of 49 showed grade I HB FN function, 5 of 49 grade II HB, and 2 of 49 grade
      III HB. Overall, in 95.9%, FN function was preserved (grade I-II HB) with stable
      results at follow-up; in 4.1% of cases, FN function was reduced, but not worse
      than grade III. CONCLUSION: The transcanal approach represents a feasible,
      minimally invasive, and conservative technique for the management of acoustic
      neuromas of the internal auditory canal.

PMID- 29227439
TI  - Assessment of Masses of the External Ear With Diffusion-Weighted MR Imaging.
AB  - PURPOSE: To assess masses of the external ear with diffusion-weighted MR imaging.
      MATERIAL AND METHODS: Retrospective analysis of 43 consecutive patients with soft
      tissue mass of the external ear. They underwent single shot diffusion-weighted MR
      imaging of the ear. The apparent diffusion coefficient (ADC) value of the mass of
      the external ear was calculated. The final diagnosis was performed by biopsy. The
      ADC value correlated with the biopsy results. RESULTS: The mean ADC value of
      malignancy (=27) of external ear (0.95 +/- 0.19 * 10 mm/s) was significantly
      lower (p = 0.001) than that of benign (n = 16) lesions (1.49 +/- 0.08 * 10 mm/s).
      The cutoff ADC used for differentiation of malignancy from benign lesions was
      1.18 * 10 mm/s with an area under the curve of 0.959, an accuracy of 93%, a
      sensitivity of 92%, and specificity of 93%. There was a significant difference in
      the ADC of well and moderately differentiated malignancy versus poorly and
      undifferentiated squamous cell carcinoma (p = 0.001), and stages I and II versus
      stages III and IV (p = 0.04) of squamous cell carcinoma. CONCLUSION: ADC value is
      a non-invasive promising imaging parameter that can be used for differentiation
      of malignancy of the external ear from benign lesions, and grading and staging of
      squamous cell carcinoma of the external ear.

PMID- 29227440
TI  - What Is the Safety and Efficacy of Chemical Venous Thromboembolism Prophylaxis
      Following Vestibular Schwannoma Surgery?
AB  - OBJECTIVE: The benefit of routine chemical prophylaxis use for venous
      thromboembolism (VTE) prevention in skull base surgery is controversial. Chemical
      prophylaxis can prevent undue morbidity and mortality, however there are risks
      for hemorrhagic complications. STUDY DESIGN: Retrospective case-control. METHODS:
      A retrospective chart review of patients who underwent surgery for vestibular
      schwannoma from 2011 to 2016 was performed. Patients were divided by receipt of
      chemical VTE prophylaxis. Number of VTEs and hemorrhagic complications
      (intracranial hemorrhage, abdominal hematoma, and postauricular hematoma) were
      recorded. RESULTS: One hundred twenty-six patients were identified, 55 received
      chemical prophylaxis, and 71 did not. All the patients received mechanical
      prophylaxis. Two patients developed a deep vein thrombosis (DVT) and one patient
      developed a pulmonary embolism (PE). All patients who developed a DVT or PE
      received chemical prophylaxis. There was no difference in DVT (p = 0.1886) or PE
      (p = 0.4365) between those who received chemical prophylaxis and those who did
      not. Five patients developed a hemorrhagic complication, two intracranial
      hemorrhage, three abdominal hematoma, and zero postauricular hematoma. All five
      patients with a complication received chemical prophylaxis (p = 0.00142). The
      relative risk of a hemorrhagic complication was 14.14 (95% CI = 0.7987-250.4307;
      p = 0.0778). CONCLUSION: There was a significant difference between the number of
      hemorrhagic complications but not between numbers of DVT or PE. Mechanical and
      chemical prophylaxis may lower the risk of VTE but in our series, hemorrhagic
      complications were observed. These measures should be used selectively in
      conjunction with early ambulation.

PMID- 29227441
TI  - Potential Risk Factors Affecting Repeated Canalith Repositioning Procedures in
      Benign Paroxysmal Positional Vertigo.
AB  - OBJECTIVE: To define the risk factors and adverse effects associated with
      repeated canalith repositioning procedures (CRPs). STUDY DESIGN: A case series
      featuring chart review. SETTING: An academic university hospital. PATIENTS: We
      retrospectively reviewed 1900 patients (average age, 54.9 years; range, 11-88
      years) diagnosed with benign paroxysmal positional vertigo (BPPV). All underwent
      repeated CRPs. We recorded clinical features including age, gender, BPPV cause
      (idiopathic or secondary), symptom duration, the canal involved, the number of
      sessions of CRP, recurrence, follow-up duration, and complications. We compared
      these factors using Pearson's chi-squared test and multiple linear regression
      analysis with dummy variables. INTERVENTIONS: BPPV was diagnosed based on the
      results of the head roll and Dix-Hallpike tests. RESULTS: The overall BPPV
      resolution rate for patients treated with repeated CRPs was 96.4%. The risk
      factors for the need for multiple CRPs in BPPV were the duration of vertigo
      before treatment (beta = 0.326, p < 0.001), the type of canal involved (beta =
      0.130, p < 0.001), and age (beta = 0.040, p = 0.040). The explanatory power of
      the regression model attained 46.0% (F = 172.510, p < 0.001). The failure rate of
      repeated CRPs was 3.6% and complications included canal conversion (3.1%), nausea
      (46.4%), vomiting (4.9%), head heaviness (50.8%), imbalance (31.9%), and
      hypotension or palpitations (8.6%). However, almost all patients recovered.
      CONCLUSION: The risk factors associated with the need for Multiple CRPs were as
      follows: longer duration of vertigo before treatment, bilateral or multiple canal
      involved, and age >50 years.

PMID- 29227442
TI  - What Is the Sensitive Period to Initiate Auditory Stimulation for the Second Ear
      in Sequential Cochlear Implantation?
AB  - OBJECTIVES: Bilateral cochlear implants (CI) are the standard treatment for
      bilaterally deaf children, but it is unclear how much the second CI can be
      delayed in sequential bilateral CI. We investigated the performances of
      sequential CI to answer this question. STUDY DESIGN: Retrospective case series
      review. SETTING: Tertiary referral center. METHODS: We studied a cohort of
      congenitally deaf children (n = 73) who underwent sequential CI without any inner
      ear anomaly or combined disabilities. Hearing threshold levels and speech
      perception were evaluated by aided pure tone audiometry and Asan-Samsung Korean
      word recognition test. The scores were analyzed by the ages at surgery and
      compared among the different age groups. RESULTS: When the second CI was
      performed before 3.5 years (the optimal period for the first CI), the second CI
      scores (96.9%) were comparable to the first CI scores. Although the first CI
      scores were more than or equal to 80% when the first CI was implanted before the
      age of 7 years, the second CI scores were more than or equal to 80% when the
      second CI was implanted before the age of 12 to 13 years. The hearing threshold
      levels were not different regardless of the ages and between the first and second
      CIs. CONCLUSION: Our cohort demonstrated that the second CI showed comparable
      results to the first CI when implanted before 3.5 years, suggesting that optimal
      periods for the first CI and the second CI are same. However, the sensitive
      period (12-13 yr) for the second CI with good scores (>=80%) was much longer than
      that (7 yr) of the first CI, suggesting that the first CI prolongs the sensitive
      period for the second CI. The second CI should be implanted early, but considered
      even at a later age.

PMID- 29227444
TI  - The Association Between Local Economic Conditions and Opioid Prescriptions Among
      Disabled Medicare Beneficiaries.
AB  - BACKGROUND: This paper concerns public health crises today-the problem of opioid
      prescription access and related abuse. Inspired by Case and Deaton's seminal work
      on increasing mortality among white Americans with lower education, this paper
      explores the relationship between opioid prescribing and local economic factors.
      OBJECTIVE: We examined the association between county-level socioeconomic factors
      (median household income, unemployment rate, Gini index) and opioid prescribing.
      SUBJECTS: We used the complete 2014 Medicare enrollment and part D drug
      prescription data from the Center for Medicare and Medicaid Services to study
      opioid prescriptions of disabled Medicare beneficiaries without record of cancer
      treatment, palliative care, or end-of-life care. MEASURES AND RESEARCH DESIGN: We
      summarized the demographic and geographic variation, and investigated how the
      local economic environment, measured by county median household income,
      unemployment rate, Gini index, and urban-rural classification correlated with
      various measures of individual opioid prescriptions. Measures included number of
      filled opioid prescriptions, total days' supply, average morphine milligram
      equivalent (MME)/day, and annual total MME dosage. To assess the robustness of
      the results, we controlled for individual and other county characteristics, used
      multiple estimation methods including linear least squares, logistic regression,
      and Tobit regression. RESULTS AND CONCLUSIONS: Lower county median household
      income, higher unemployment rates, and less income inequality were consistently
      associated with more and higher MME opioid prescriptions among disabled Medicare
      beneficiaries. Geographically, we found that the urban-rural divide was not
      gradual and that beneficiaries in large central metro counties were less likely
      to have an opioid prescription than those living in other areas.

PMID- 29227445
TI  - Mobile Hearing Testing Applications and the Diagnosis of Sudden Sensorineural
      Hearing Loss: A Cautionary Tale.
AB  - OBJECTIVE: Mobile hearing applications (apps) are available for hearing testing,
      personal sound amplification, as well as hearing aid modulation. Hearing testing
      apps are gaining popularity, especially in resource-limited settings. The
      reliability of mobile hearing testing apps, however, is not well characterized.
      PATIENTS/INTERVENTIONS: A case study of a single patient with a complaint of
      sudden hearing loss presenting to a tertiary-care hospital. MAIN OUTCOME MEASURE:
      Comparison of a mobile hearing testing app results with standard audiogram.
      RESULTS: A commercially available mobile hearing testing app was used after hours
      to determine if a patient's hearing complaints were consistent with sudden
      sensorineural hearing loss. The hearing app produced a rudimentary audiogram that
      was consistent with unilateral SSNHL. Given contraindications to oral treatment,
      preparations for possible intratympanic dexamethasone after a full audiometric
      evaluation were completed. Confirmatory audiogram the following day demonstrated
      normal hearing without evidence of hearing loss. Steroid treatment was aborted
      and appropriate counseling provided. CONCLUSION: While mobile hearing testing
      apps offer improved access to hearing screening in resource-limited settings,
      caution must be exercised when interpreting data and making clinical decisions
      based upon results. The role of professional audiologists remains critical.
      Further testing and validation of specific apps is required.

PMID- 29227443
TI  - Associations Between Medicare Part D and Out-of-Pocket Spending, HIV Viral Load,
      Adherence, and ADAP Use in Dual Eligibles With HIV.
AB  - BACKGROUND: The implementation of Medicare part D on January 1, 2006 required all
      adults who were dually enrolled in Medicaid and Medicare (dual eligibles) to
      transition prescription drug coverage from Medicaid to Medicare part D. Changes
      in payment systems and utilization management along with the loss of Medicaid
      protections had the potential to disrupt medication access, with uncertain
      consequences for dual eligibles with human immunodeficiency virus (HIV) who rely
      on consistent prescription coverage to suppress their HIV viral load (VL).
      OBJECTIVE: To estimate the effect of Medicare part D on self-reported out-of
      pocket prescription drug spending, AIDS Drug Assistance Program (ADAP) use,
      antiretroviral adherence, and HIV VL suppression among dual eligibles with HIV.
      METHODS: Using 2003-2008 data from the Women's Interagency HIV Study, we created
      a propensity score-matched cohort and used a difference-in-differences approach
      to compare dual eligibles' outcomes pre-Medicare and post-Medicare part D to
      those enrolled in Medicaid alone. RESULTS: Transition to Medicare part D was
      associated with a sharp increase in the proportion of dual eligibles with self
      reported out-of-pocket prescription drug costs, followed by an increase in ADAP
      use. Despite the increase in out-of-pocket costs, both adherence and HIV VL
      suppression remained stable. CONCLUSIONS: Medicare part D was associated with
      increased out-of-pocket spending, although the increased spending did not seem to
      compromise antiretroviral therapy adherence or HIV VL suppression. It is possible
      that increased ADAP use mitigated the increase in out-of-pocket spending,
      suggesting successful coordination between Medicare part D and ADAP as well as
      the vital role of ADAP during insurance transitions.

PMID- 29227446
TI  - Meta-analysis of Cochlear Implantation Outcomes Evaluated With General Health
      related Patient-reported Outcome Measures.
AB  - OBJECTIVE: Determine the change in general health-related quality of life (HRQOL)
      after cochlear implantation and association with speech recognition. STUDY
      DESIGN: Meta-analysis. METHODS: Search was performed following the PRISMA
      statement using PubMed, Medline, Scopus, and CINAHL. Studies on adult cochlear
      implant (CI) patients measuring HRQOL before and after cochlear implantation were
      included. Standardized mean difference (SMD) for each measure and pooled effects
      were determined. A meta-analysis of correlations was also performed between all
      non-disease-specific patient-reported outcome measures (PROMs) and speech
      recognition after cochlear implantation. RESULTS: Twenty-two articles met
      criteria for meta-analysis of HRQOL improvement, but 15 (65%) were excluded due
      to incomplete statistical reporting. From the seven articles with 274 CI patients
      that met inclusion criteria, pooled analyses showed a medium positive effect of
      cochlear implantation on HRQOL (SMD = 0.79). Subset analysis of the HUI-3 measure
      showed a large effect (SMD = 0.84). Nine articles with 550 CI patients met
      inclusion criteria for meta-analysis of correlations between non-disease specific
      PROMs and speech recognition after cochlear implantation. Pooled analysis showed
      a low correlation between non-disease-specific PROMs and word recognition in
      quiet (r = 0.35), sentence recognition in quiet (r = 0.40), and sentence
      recognition in noise (r = 0.32). CONCLUSION: Although regularly used, HRQOL
      measures are not intended to measure nor do they accurately reflect the complex
      difficulties facing CI patients. Only a medium positive effect of cochlear
      implantation on HRQOL was observed along with a low correlation between non
      disease-specific PROMs and speech recognition. The use of such instruments in
      this population may underestimate the benefit of cochlear implantation.

PMID- 29227447
TI  - Heat Shock Proteins in Human Perilymph: Implications for Cochlear Implantation.
AB  - OBJECTIVE: Biomarkers reflecting the etiology and pathophysiology of inner ear
      diseases are limited. Evaluation of proteins in the perilymph may improve our
      understanding of inner ear disease. Heat shock proteins (HSP) belong to a
      superfamily of stress proteins and promote refolding of denatured proteins. The
      aim of the study was to analyze HSP in human perilymph and to identify possible
      correlation with audiological and etiologic data. METHODS: Sampling of the
      perilymph was performed during cochlear implantation and vestibular schwannoma
      removal. Individual proteins were identified by a shot-gun proteomics approach by
      orbitrap mass spectrometry. Expression of HSP genes was determined in human
      cochlear tissue that was obtained during transcochlear surgeries. RESULTS: Ten
      subgroups of HSP were identified in human perilymph samples. Increased levels of
      HSP were detected in a higher percentage in the perilymph of patients with
      residual hearing when compared with patients with no residual hearing in cochlear
      implantation. In patients with complete preservation of residual hearing, HSP 90
      is identified in a lower percentage whereas HSP 70 1A/1B and 6 was identified in
      all the samples. Constitutive expression of HSP family members was verified in
      normal cochlear tissue. CONCLUSION: The 10 HSP variants are not identified in all
      the perilymph samples, but in a higher proportion in patients with residual
      hearing compared with patients with no residual hearing. In-depth proteome
      analysis of perilymph samples in correlation to patients' audiogram data shows an
      increased concentration of HSP in patients with residual hearing. An increase in
      specific HSP in patients with loss of residual hearing after cochlear
      implantation was not observed.

PMID- 29227448
TI  - Cochlear Implantation in Chronic Otitis Media With Cholesteatoma and Open
      Cavities: Long-term Surgical Outcomes.
AB  - OBJECTIVES: To evaluate the long-term surgical outcomes of cochlear implantation
      (CI) in chronic otitis media (COM) with cholesteatoma and open cavities using
      subtotal petrosectomy (STP). To review device explantation (DE) patients and
      reimplantation considerations. STUDY DESIGN: Retrospective review. SETTING:
      Otology and skull base center. PATIENTS AND METHODS: Charts of 35 patients (36
      ears) with COM with cholesteatoma, including open cavities, who underwent CI were
      reviewed for surgical outcomes and DE. Patient demographics, pathologies,
      previous surgeries, staging of implantation, salient intraoperative findings at
      the time of implantation and follow-up were evaluated. Details of patients with
      DE were evaluated for cause, operative findings, and reimplantation
      considerations. RESULTS: Mean age of patients was 65.94 years. Nineteen open
      cavities, 11 primary cholesteatomas, 3 petrous bone cholesteatomas, and 3
      atelectatic middle ears represented the pathologies with 31 patients of CI with
      concurrent STP and 5 patients where implantation was staged. The mean follow-up
      was 7.16 years ranging from 2 to 13 years. Four patients (11%) had DE due to
      extrusion and cavity infection with three reimplanted in same or contralateral
      ear. All explantations occurred within 24 months of primary implantation. No
      residual or recurrent cholesteatoma was observed in any of the patients during
      follow-up. CONCLUSION: CI is feasible in COM with cholesteatoma and open cavities
      with the use of STP and single-stage implantation can be performed in the absence
      of purulence. Despite low risk of residual cholesteatoma post meticulous disease
      removal, risk of DE remains, particularly in open cavity patients, and is higher
      than standard implantation. Reimplantation is often possible with careful
      considerations.

PMID- 29227449
TI  - Early Outcomes With a Slim, Modiolar Cochlear Implant Electrode Array.
AB  - OBJECTIVE: To describe outcomes from cochlear implantation with a new, slim
      modiolar electrode array. STUDY DESIGN: Retrospective cohort study. SETTING:
      Tertiary referral centers. PATIENTS: Adult cochlear implant candidates.
      INTERVENTIONS: Cochlear implantation with CI532 (Cochlear Corp). MAIN OUTCOME
      MEASURES: Pre- and postoperative speech perception scores, operative details, and
      postoperative computed tomography (CT) reconstructions of array location.
      RESULTS: One hundred seventeen patients are implanted to date. There were eight
      tip rollovers identified with intraoperative x-ray and resolved with reinsertion.
      An additional rollover was identified on postoperative CT. CT reconstructions in
      17 of 23 patients showed complete scala tympani placement with a wrap factor of
      58% (range 53-64%) and a mean insertion angle of 406 degrees (range 360-452
      degrees). Three implants demonstrated array translocation with electrodes in the
      scala vestibuli. Consonant-nucleus-consonant word scores improved from 10%
      preoperatively to 48% at 3 months postoperatively. Pure-tone thresholds were
      preserved postoperatively in 37 to 52% of patients across frequencies from 250 to
      4000 Hz. Functional pure-tone thresholds (<=80 dB) were recorded in 9 to 25% of
      patients. CONCLUSION: CI532 array insertion results in consistent scala tympani
      location and provides expected audiologic performance. Initial hearing
      preservation results are not consistent with current electro-acoustic arrays.

PMID- 29227450
TI  - Hearing Loss in Pediatric Patients With Cerebral Palsy.
AB  - OBJECTIVE: This study evaluates the prevalence, type, and severity of hearing
      impairment in children with cerebral palsy (CP) and to analyze audiologic and
      otologic outcomes in these patients. STUDY DESIGN: Retrospective analysis of the
      AudGen Database. SETTING: Tertiary academic referral center. PATIENTS: Pediatric
      patients in AudGen Database with a diagnosis of cerebral palsy. Appropriate
      audiologic, otologic, and demographic data were recorded.Nine hundred forty
      patients met inclusion criteria. Hearing loss (HL) was defined as greater than 15
      dB HL at any threshold by pure tone or greater than 20 dB HL by soundfield
      audiometry. Other available otologic and medical conditions were documented.
      RESULTS: Of 940 patients, 367 (39%) had hearing loss. Of the 1,629 individual
      ears with HL, 782 (48%) had conductive, 63 (4%) had sensorineural, 410 (25%) had
      mixed, and 374 (23%) had unspecified hearing loss. Patients with mixed type 1
      hearing loss had significantly worse PTAs. INTERPRETATION: Hearing loss in CP has
      a large degree of sensorineural loss, with a predisposition to be bilateral. The
      severity of hearing loss was correlated with the degree of the motor and
      neurologic disability in these patients.

PMID- 29227451
TI  - Cartilage Conduction Hearing Aids for Severe Conduction Hearing Loss.
AB  - OBJECTIVE: To assess the benefits of a new type of hearing aid using cartilage
      conduction (CC) in patients with severe conduction hearing loss and evaluate its
      potential for practical use. STUDY DESIGN: Consecutive, prospective case series.
      PATIENTS: Forty-one subjects (21 with bilateral aural atresia; 15 with unilateral
      aural atresia; and 5 others) participated in this study. INTERVENTION: Fitting
      and gain adjustments of the CC hearing aids were performed to the ear(s) with
      conduction hearing loss. MAIN OUTCOME MEASURES: The function gains were measured.
      Evaluation of the measurements of speech performance-intensity functions, speech
      recognition scores, tolerance of environmental noise, and subject questionnaires
      were also performed, and judged according to the "Guidelines for the evaluation
      of hearing aid fitting" established by the Japan Audiological Society. RESULTS:
      The thresholds were significantly improved by CC hearing aids. The functional
      gains for CC hearing aids were nearly equivalent to that for their previously
      used hearing aids. The style of the transducer fixation and the type of aural
      atresia had no significant influence on the functional gains. Most of the
      assessment results were judged to be sufficient. Before the trial, bone
      conduction hearing aids had been used most frequently by bilateral aural atresia
      subjects. However, after the trial, most subjects continued to use CC hearing
      aids instead of reverting back to their original device. Overall, 39 subjects
      continued use of the CC hearing aids. No severe adverse effects were noted in the
      trial. CONCLUSION: Cartilage conduction hearing aids could be an additional and
      beneficial option for severe conduction hearing loss from aural atresia.

PMID- 29227452
TI  - High Resolution Three-Dimensional Delayed Contrast MRI Detects Endolymphatic
      Hydrops in Patients With Vertigo and Vestibular Schwannoma.
AB  - OBJECTIVE: Advances in high resolution magnetic resonance imaging (MRI) have
      enabled the detection of endolymphatic hydrops (EH), a pathological ballooning of
      the endolymphatic fluid system, known to be associated with Meniere's disease.
      When a patient has a known diagnosis of vestibular schwannoma and develops
      recurrent episodic vertigo spells, many surgeons recommend surgical intervention,
      attributing the vestibular symptoms to the vestibular schwannoma. The aim of this
      study is to evaluate the clinical outcome in patients with vestibular schwannoma
      and EH, treated medically, for recurrent spells of vertigo. PATIENTS: Two
      patients with EH and vestibular schwannoma who presented with recurrent spells of
      vertigo are included. Both had characteristic low frequency hearing loss
      ipsilateral to the schwannoma. INTERVENTION: MRI sequences with 3T scanner
      (Skyra, Siemens Healthcare, Erlangen, Germany) using high resolution three
      dimensional delayed postcontrast protocol included "cisternographic" T2 and
      delayed intravenous-enhanced three-dimensional fluid-attenuation inversion
      recovery (DIVE-3D-FLAIR) sequences, performed with 2350 ms (bright perilymph) and
      2050 ms (bright endolymph) inversion times and with subtracted images. MAIN
      OUTCOME MEASURE: MRI FLAIR evaluation of EH and presence or absence of vestibular
      symptoms. RESULTS: Both patients had resolution of the disabling vertigo spells
      with a diuretic, and Patient 1 had unchanged EH, while Patient 2 had partial
      resolution of the EH and the FLAIR hyperintensity. CONCLUSION: When EH coexists
      with vestibular schwannoma in a patient presenting with recurrent vertigo spells,
      medical treatments for EH may alleviate the vestibular symptoms. We recommend
      that patients with small vestibular schwannomas who present with vertigo spells
      undergo high resolution MRI to evaluate for EH and undergo a trial of medical
      treatment with diuretics.

PMID- 29227453
TI  - Effect of Prophylactic Medication on Associated Dizziness and Motion Sickness in
      Migraine.
AB  - OBJECTIVE: To determine the efficacy of prophylactic medications for migraine in
      reducing associated dizziness and motion sickness. STUDY DESIGN: Multicenter
      prospective observational study. SETTING: Nationwide 9 Dizziness Clinics in South
      Korea. PATIENTS: One hundred thirty-eight patients who required a preventive
      medication for migraine accompanied by dizziness and motion sickness.
      INTERVENTION: At least one of the prophylactic medications was prescribed among
      the beta-blockers, calcium channel blockers, tricyclic antidepressants, and
      antiepileptic drugs. MAIN OUTCOME MEASURE: For 3 months from the index visit, the
      patients had monthly assessments of the headache (frequency and duration),
      dizziness handicap inventory, University of California Los Angeles dizziness
      questionnaire, vertigo symptom scale, and motion sickness score. RESULTS: The
      prophylactic medications significantly improved the headache profiles, all three
      parameters of dizziness (dizziness handicap inventory, University of California
      Los Angeles dizziness questionnaire, and vertigo symptom scale), and severity of
      motion sickness (p < 0.001). CONCLUSION: The prophylactic medication for migraine
      also improves associated dizziness and motion sickness as well as the headaches.

PMID- 29227454
TI  - Immediate and Long-term Hearing Outcomes With the Middle Cranial Fossa Approach
      for Vestibular Schwannoma Resection.
AB  - OBJECTIVE: To analyze the immediate postoperative and long-term hearing outcome
      data in patients who have undergone hearing preservation attempts with the middle
      cranial fossa (MCF) approach for the resection of sporadic vestibular schwannoma.
      STUDY DESIGN: Retrospective review of a surgical patient cohort. SETTING:
      Tertiary academic referral center. PATIENTS: Adult patients with unilateral
      sporadic vestibular schwannoma. INTERVENTION: Surgical treatment with a MCF
      approach. MAIN OUTCOME MEASURE: Comparison of pre- and postoperative audiometric
      data in accordance with the 1995 and 2012 American Academy of Otolaryngology/Head
      and Neck Surgery guidelines on reporting hearing outcomes and with a word
      recognition score only scale. Long-term hearing outcome data were analyzed in the
      following postoperative groups: 3 to 5, 6 to 8, 9 to 11, and 12+ years after
      surgery. RESULTS: From 1999 to 2016, 174 patients underwent the MCF approach and
      155 of them met inclusion criteria for analysis of hearing outcome data. Class A
      or B hearing was preserved in 70% of the entire cohort after recovery. Seventy
      one patients with measurable hearing met criteria for long-term data analysis.
      The rate of American Academy of Otolaryngology/Head and Neck Surgery class A or B
      hearing preservation was 82% at 3 to 5 years and declined thereafter. The rate of
      word recognition score class I or II hearing preservation was 98% at 3 to 5 years
      and declined less rapidly thereafter. Patients with preoperative Class A hearing
      had significantly higher rates of successful hearing preservation at all
      postoperative intervals. CONCLUSION: Delayed hearing loss occurs in a
      progressively increasing fashion but speech understanding remains durable for a
      majority of patients whose hearing is initially preserved with the MCF approach.

PMID- 29227455
TI  - Electrophysiological Evaluation of the Facial Muscles in Congenital Unilateral
      Lower Lip Palsy.
AB  - OBJECTIVES: Congenital unilateral lower lip palsy (CULLP) is a congenital facial
      asymmetry in which one corner of the mouth does not dip downward symmetrically
      (Kobayashi, 1979). We analyzed the electrophysiological findings in cases of
      CULLP to understand the facial nerve mechanisms underlying this pathological
      condition. METHODS: The electrophysiological findings in 20 patients with CULLP
      including an electroneuronography (ENoG) of the orbicularis oris muscle, nerve
      excitability test (NET) results, and the blink reflex (BR) were analyzed.
      RESULTS: Of 21 patients with CULLP, 20 underwent ENoG, 12 underwent a NET, and 14
      underwent a BR examination. Nine of 19 patients with CULLP showed higher ENoG
      amplitude in the affected side than in the unaffected side. In four patients, the
      ENoG amplitude in the affected side was similar to that in the unaffected side
      whereas six patients had higher ENoG amplitude in the unaffected side. All
      patients showed a normal BR response and only one patient had a left-right
      difference in the NET response in the marginal mandibular branch. NET also
      demonstrated that the muscular twitch appeared on the lower lip of the affected
      side. CONCLUSION: These results suggested that in CULLP, each of the facial nerve
      branches including the marginal mandibular branch appeared to function within
      normal parameters. The marginal mandibular branch of the facial nerve, which
      usually innervates the depressor anguli oris and depressor labii inferioris
      muscles, may innervate adjacent muscles as well, such as the orbicularis oris
      muscle, during prenatal development.

PMID- 29227457
TI  - Spontaneous Pnemocephalus Associated With Defects on the Tegmen Mastoideum.

PMID- 29227456
TI  - Photopolymerized Microfeatures Guide Adult Spiral Ganglion and Dorsal Root
      Ganglion Neurite Growth.
AB  - HYPOTHESIS: Microtopographical patterns generated by photopolymerization of
      methacrylate polymer systems will direct growth of neurites from adult neurons,
      including spiral ganglion neurons (SGNs). BACKGROUND: Cochlear implants (CIs)
      provide hearing perception to patients with severe to profound hearing loss.
      However, their ability to encode complex auditory stimuli is limited due, in
      part, to poor spatial resolution caused by spread of the electrical currents in
      the inner ear. Directing the regrowth of SGN peripheral processes towards
      stimulating electrodes could help reduce current spread and improve spatial
      resolution provided by the CI. Previous work has demonstrated that micro- and
      nano-scale patterned surfaces precisely guide the growth of neurites from a
      variety of neonatal neurons including SGNs. Here, we sought to determine the
      extent to which adult neurons likewise respond to these topographical surface
      features. METHODS: Photopolymerization was used to fabricate methacrylate polymer
      substrates with micropatterned surfaces of varying amplitudes and periodicities.
      Dissociated adult dorsal root ganglion neurons (DRGNs) and SGNs were cultured on
      these surfaces and the alignment of the neurite processes to the micropatterns
      was determined. RESULTS: Neurites from both adult DRGNs and SGNs significantly
      aligned to the patterned surfaces similar to their neonatal counterparts. Further
      DRGN and SGN neurite alignment increased as the amplitude of the microfeatures
      increased. Decreased pattern periodicity also improved neurite alignment.
      CONCLUSION: Microscale surface topographic features direct the growth of adult
      SGN neurites. Topographical features could prove useful for guiding growth of SGN
      peripheral axons towards a CI electrode array.

PMID- 29227458
TI  - Unilateral Sensorineural Hearing Loss Associated With Vertebrobasilar
      Dolichoectasia.

PMID- 29227459
TI  - Otosclerosis With Concomitant Anterior Malleolar Ligament Fixation.

PMID- 29227460
TI  - Neuropathic-Like Ocular Pain and Nonocular Comorbidities Correlate With Dry Eye
      Symptoms.
AB  - OBJECTIVE: To evaluate the association between dry eye (DE) symptoms and
      neuropathic-like ocular pain (NOP) features, chronic pain conditions, depression,
      and anxiety in patients presenting for routine ophthalmic examinations. METHODS:
      Two hundred thirty-three consecutive patients >=18 years of age presenting to a
      comprehensive eye clinic between January and August 2016 were included in this
      study. Information on demographics, chronic pain conditions, medication use, DE
      symptoms (dry eye questionnaire, DEQ5), NOP complaints (burning; wind, light, and
      temperature sensitivity), depression, and anxiety indices (patient health
      questionnaire 9, PHQ-9 and symptom checklist 90-revised, SCL-90-R) were collected
      for each individual. Pearson correlation was used to evaluate strengths of
      association. Logistic regression analysis examined risk factors for any (DEQ5>=6)
      and severe (DEQ5>=12) DE symptoms. RESULTS: The mean age of the population was
      46.3 years (+/-13.0); 67.8% (n=158) were female. Per the DEQ5, 40.3% (n=94) had
      mild or greater DE symptoms and 12% (n=24) had severe symptoms. Severity of DE
      symptoms correlated with NOP complaints: burning (Pearson r=0.37, P<0.001);
      sensitivity to wind (r=0.37, P<0.001), sensitivity to light (r=0.34, P<0.001),
      and sensitivity to temperature (r=0.30, P<0.001). Sex, race, and ethnicity were
      not significant risk factors for DE symptoms. Risk factors for mild or greater DE
      symptoms included a greater number of chronic nonocular pain conditions (odds
      ratio [OR]=1.38, P<0.001), arthritic pain (OR=6.34, P<0.001), back pain (OR=2.47,
      P=0.004), headaches (OR=2.14, P=0.02), depression (OR=1.17, P<0.001), and anxiety
      (OR=1.13, P=0.02). CONCLUSION: Dry eye severity positively associated with NOP
      complaints, comorbid chronic pain conditions, and symptoms of depression and
      anxiety.

PMID- 29227461
TI  - Population Pharmacokinetics of Lopinavir in Severely Malnourished HIV-infected
      Children and the Effect on Treatment Outcomes.
AB  - BACKGROUND: In developing countries, malnutrition remains a common clinical
      syndrome at antiretroviral treatment (ART) initiation. Physiologic changes
      because of malnutrition and during nutritional recovery could affect the
      pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted
      with severe acute malnutrition were randomized to early or delayed initiation of
      lopinavir (LPV)/ritonavir, abacavir and lamivudine using World Health
      Organization weight band dosage charts. LPV concentrations were measured on day 1
      and day 14. Thereafter, patients were followed-up to week 48. The population
      pharmacokinetics of LPV was described using NONMEM v7.3. Covariates were screened
      to assess their influence on the pharmacokinetics of LPV, and the relationship
      between pharmacokinetic variability and treatment outcomes were assessed.
      RESULTS: Five hundred and two LPV concentrations were collected from 62 pediatric
      patients 0.1-3.9 years of age (median: 0.9 years). Rifampin-based
      antituberculosis treatment and "super-boosted" LPV/ritonavir were prescribed in
      20 patients. LPV disposition was well described by a one-compartment model with
      first-order elimination. Neither randomization to early or delayed ART,
      tuberculosis comedications nor anthropometrical measurements explained the
      pharmcokinetic variability. Allometrically scaled fat-free mass influenced
      apparent clearance (CL/F) and volume of distribution (Vd/F). Pharmacokinetic
      exposure did not correlate with virologic outcomes or death at 12 or 48 weeks.
      CONCLUSIONS: LPV pharmacokinetics was influenced by fat-free mass and not by
      timing of ART initiation or tuberculosis comedication in severely malnourished
      HIV-infected children. LPV pharmacokinetics was found to be highly variable and
      bioavailability greatly reduced, resulting in a high CL estimate in this
      population. The role of LPV dose adjustment should be further evaluated in
      severely malnourished children initiating ART.

PMID- 29227463
TI  - The Conquest of Hib - The Importance of Protecting High Risk Children.

PMID- 29227462
TI  - Psychiatric Disorders, Antiretroviral Medication Adherence and Viremia in a
      Cohort of Perinatally HIV-Infected Adolescents and Young Adults.
AB  - BACKGROUND: Perinatally HIV-infected (PHIV+) adolescents and young adults (AYA)
      are at risk for suboptimal antiretroviral therapy (ART) adherence and mental
      health and substance use problems that, in HIV-infected adults, predict
      nonadherence. Studies on the relationship between psychiatric and substance use
      disorders (SUD) and adherence among PHIV+ AYA are limited, but may be important
      for informing evidence-based interventions to promote adherence. METHODS: Data
      were analyzed from 3 annual follow-up interviews (FU2-FU4, N = 179) in a
      longitudinal study of PHIV+ AYA. Psychiatric disorders (anxiety, disruptive
      behavior, mood and SUD) were assessed with the Diagnostic Interview Schedule for
      Children. Adherence was self-reported missed ART doses within the past week.
      Viral load (VL) results were abstracted from medical charts. Multiple logistic
      regression analyzed cross-sectional associations between psychiatric disorders
      and (1) missed ART dose and (2) VL > 1000 copies/mL. Multiple linear regression
      assessed associations between psychiatric disorders and proportion of VL values
      >1000 copies/mL over time. RESULTS: At FU2, 53% of PHIV+ AYA had any psychiatric
      disorder, 35% missed an ART dose in the past week and 47% had a VL > 1000
      copies/mL. At FU2, behavioral disorders were associated with missed dose (P =
      0.009) and VL > 1000 (P = 0.019), and mood disorders were associated with missed
      dose (P = 0.041). At FU4, behavioral disorders were associated with missed dose
      (P = 0.009). Behavioral disorders (P = 0.041), SUD (P = 0.016) and any disorder
      (P = 0.008) at FU2 were associated with higher proportion of VLs >1000 across FU2
      FU4. CONCLUSIONS: Addressing psychiatric disorder and SUD among PHIV+ AYA may
      improve ART adherence outcomes in this population. Targeted interventions should
      be developed and tested.

PMID- 29227464
TI  - Antibiotic Resistance of Potential Otopathogens Isolated From Nasopharyngeal
      Flora of Children With Acute Otitis Media Before, During and After Pneumococcal
      Conjugate Vaccines Implementation.
AB  - BACKGROUND: To re-evaluate antibiotic strategies for acute otitis media (AOM) in
      young children, we analyzed the trends of nasopharyngeal carriage and antibiotic
      resistance of Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi) and
      Moraxella catarrhalis (Mc) isolated from young children with AOM during a 16-year
      period. METHODS: This cross-sectional study analyzed from 2001 to 2016 the
      nasopharyngeal carriage of Sp, Hi and Mc of young children with AOM. Medical
      history and physical findings were reported. Periods were defined by pneumococcal
      conjugate vaccine (PCV) introduction. We separately analyzed the 13-valent PCV
      (PCV13) period, which started after 2013. RESULTS: During the study, 12,973
      children with AOM were enrolled by 138 pediatricians. By comparing the first and
      last PCV periods, the proportion of children in day care centers and that of AOM
      with conjunctivitis significantly increased. The proportion of penicillin
      nonsusceptible Sp carriage significantly decreased during the study, with 0.8% of
      penicillin-resistant strains isolated in the PCV13 period, but that of beta
      lactamase-producing Hi continually increased to 23.6% in 2016. The level of Mc
      beta-lactamase-producing strains remained high (>97%). In the PCV13 period, the
      main predictors of beta-lactamase-producing Hi carriage were conjunctivitis
      (adjusted odds ratio = 6.0, 95% confidence interval [4.7-7.7]) and attending a
      day care center (2.4 [1.7-3.5]). CONCLUSIONS: In the PCV13 period, the proportion
      of penicillin-resistant Sp carriage was very low and that of beta-lactamase
      producing Hi carriage did not exceed 20% among children with AOM and without
      conjunctivitis. Our results suggest that amoxicillin may remain the first-line
      antibiotic treatment for AOM in young children except for those with
      conjunctivitis, for which amoxicillin-clavulanate is still the best antibiotic.

PMID- 29227465
TI  - Acute Pharyngitis Associated With Streptococcus dysgalactiae Subspecies
      equisimilis in Children.
AB  - BACKGROUND AND OBJECTIVES: The importance of Streptococcus dysgalactiae subsp.
      equisimilis (SDSE) in causing sporadic pharyngitis in children remains
      controversial. The aims of this study were (1) to report the incidence and (2) to
      compare the epidemiologic and clinical features of patients with SDSE to those
      with Streptococcus pyogenes (SP). METHODS: A prospective study was conducted on
      acute pharyngitis associated with SDSE in children over a 2-year period. SDSE was
      identified using a phenotypic method, M protein gene (emm) analysis and matrix
      assisted laser desorption ionization-time of flight mass spectrometry. Patients
      with positive SDSE or SP cultures received cephalosporins for 5 days and were
      followed up. The emm genotyping and specific virulence genes analyses were
      performed. RESULTS: From 3416 throat cultures, 67 isolates (2.0%) were identified
      as SDSE and 515 (15.1%) were identified as SP. The mean age of patients with SDSE
      (8.3 years) was older than those with SP (6.6 years; P < 0.01). There was minimal
      seasonal variation in the isolation rates of SDSE. The febrile patients' rates,
      gender distribution, cervical lymph node adenopathy rates, hospitalization rates,
      eradication and failure rates and the nonsuppurative sequelae between patients
      with SDSE and SP were similar. All SDSE isolates possessed important virulence
      genes. The emm genotyping of SDSE showed high strain diversity. CONCLUSIONS: The
      incidence of acute pharyngitis associated with accurately identified SDSE was
      2/15 of that with SP. Epidemiologic and clinical features of acute pharyngitis
      associated with SDSE are indistinguishable from those with SP, with the exception
      of age and seasonal variation.

PMID- 29227466
TI  - Morbidity and Mortality of a Cohort of Peruvian HIV-infected Children 2003-2012.
AB  - BACKGROUND: Data on pediatric HIV in Peru are limited. The National Institute of
      Child Health (Instituto Nacional de Salud del Nino: INSN) cares for the most HIV
      infected children under the age of 18 years in the country. We describe the
      outcomes of children seen at INSN's HIV clinic over the 10 years when
      antiretroviral therapy and prevention of mother-to-child transmission (PMTCT)
      interventions became available in 2004. METHODS: We conducted a retrospective
      review of INSN HIV clinic patients between 2003 and 2012. Deidentified data were
      collected and analyzed. RESULTS: A total of 280 children were included: 50.0%
      (140/280) were male; 80.0% (224/280) lived in metropolitan Lima. Perinatal
      transmission was the mode of HIV infection in 91.4% (256/280) of children. Only
      17% (32/191) of mothers were known to be HIV-infected at delivery; of these
      mothers, 41% (13/32) were receiving antiretroviral therapy at delivery, 72%
      (23/32) delivered by Cesarean section and 47% (15/32) of their infants received
      antiretroviral prophylaxis. Median age at HIV diagnosis for all children was 35.7
      months (interquartile range 14.5-76.8 months), and 67% (143/213) had advanced
      disease (clinical stage C). After HIV diagnosis, the most frequent
      hospitalization discharge diagnoses were bacterial pneumonia, chronic
      malnutrition, diarrhea, anemia and tuberculosis. Twenty-four patients (8.6%) died
      at a median age of 77.4 months. CONCLUSIONS: Most cases of pediatric HIV were
      acquired via perinatal transmission; few mothers were diagnosed before delivery;
      and among mothers with known HIV status, PMTCT was suboptimal even after national
      PMTCT policy was implemented. Most children were diagnosed with advanced disease.
      These findings underscore the need for improving early pediatric HIV diagnosis
      and treatment, as well as PMTCT strategies.

PMID- 29227467
TI  - Evidence for Rise in Meningococcal Serogroup C Bactericidal Antibody Titers in
      the Absence of Booster Vaccination in Previously Vaccinated Children.
AB  - BACKGROUND: The introduction of meningococcal serogroup C (MenC) conjugate
      vaccines in the United Kingdom and Australia led to an impressive decline in the
      incidence of invasive disease. This study examined bactericidal antibody titers
      over time in the UK and Australian children who received a MenC conjugate vaccine
      in early childhood to test the hypothesis that ongoing boosting of immunity in
      the absence of further doses of vaccine in some children may contribute to
      ongoing protection from disease. METHODS: Serum bactericidal assay using rabbit
      complement (rSBA) titers at each follow-up visit were compared with all preceding
      visits to identify any >=4-fold rise in titers. The proportion of children with a
      >=4-fold rise in rSBA titers in paired sera at any visit-to-visit comparison was
      calculated. RESULTS: Of 392 children with at least one set of paired sera in the
      Australian cohort, 72 (18.4%) had a >=4-fold increase in rSBA titers at least one
      year after vaccination, including six children (1.5%) who showed evidence of
      boosting twice. Of 234 children with at least one set of paired sera in the UK
      cohort, 39 (16.7%) had a >=4-fold rise in rSBA titers at least one year after
      vaccination including 2 children (0.9%) with evidence of boosting twice.
      CONCLUSIONS: A substantial minority of children immunized with MenC conjugate
      vaccine in early childhood had a rise in bactericidal antibody titers in the
      years after immunization in the absence of booster vaccination. This occurs most
      commonly at around 6-7 years of age corresponding to school entry and greater
      social mixing and might indicate exposure to MenC carriage.

PMID- 29227468
TI  - Metagenomic binning and association of plasmids with bacterial host genomes using
      DNA methylation.
AB  - Shotgun metagenomics methods enable characterization of microbial communities in
      human microbiome and environmental samples. Assembly of metagenome sequences does
      not output whole genomes, so computational binning methods have been developed to
      cluster sequences into genome 'bins'. These methods exploit sequence composition,
      species abundance, or chromosome organization but cannot fully distinguish
      closely related species and strains. We present a binning method that
      incorporates bacterial DNA methylation signatures, which are detected using
      single-molecule real-time sequencing. Our method takes advantage of these
      endogenous epigenetic barcodes to resolve individual reads and assembled contigs
      into species- and strain-level bins. We validate our method using synthetic and
      real microbiome sequences. In addition to genome binning, we show that our method
      links plasmids and other mobile genetic elements to their host species in a real
      microbiome sample. Incorporation of DNA methylation information into shotgun
      metagenomics analyses will complement existing methods to enable more accurate
      sequence binning.

PMID- 29227469
TI  - Integrative single-cell analysis of transcriptional and epigenetic states in the
      human adult brain.
AB  - Detailed characterization of the cell types in the human brain requires scalable
      experimental approaches to examine multiple aspects of the molecular state of
      individual cells, as well as computational integration of the data to produce
      unified cell-state annotations. Here we report improved high-throughput methods
      for single-nucleus droplet-based sequencing (snDrop-seq) and single-cell
      transposome hypersensitive site sequencing (scTHS-seq). We used each method to
      acquire nuclear transcriptomic and DNA accessibility maps for >60,000 single
      cells from human adult visual cortex, frontal cortex, and cerebellum. Integration
      of these data revealed regulatory elements and transcription factors that
      underlie cell-type distinctions, providing a basis for the study of complex
      processes in the brain, such as genetic programs that coordinate adult
      remyelination. We also mapped disease-associated risk variants to specific
      cellular populations, which provided insights into normal and pathogenic cellular
      processes in the human brain. This integrative multi-omics approach permits more
      detailed single-cell interrogation of complex organs and tissues.

PMID- 29227470
TI  - Multiplexed droplet single-cell RNA-sequencing using natural genetic variation.
AB  - Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively
      parallel profiling of transcriptomes. However, assessing differential expression
      across multiple individuals has been hampered by inefficient sample processing
      and technical batch effects. Here we describe a computational tool, demuxlet,
      that harnesses natural genetic variation to determine the sample identity of each
      droplet containing a single cell (singlet) and detect droplets containing two
      cells (doublets). These capabilities enable multiplexed dscRNA-seq experiments in
      which cells from unrelated individuals are pooled and captured at higher
      throughput than in standard workflows. Using simulated data, we show that 50
      single-nucleotide polymorphisms (SNPs) per cell are sufficient to assign 97% of
      singlets and identify 92% of doublets in pools of up to 64 individuals. Given
      genotyping data for each of eight pooled samples, demuxlet correctly recovers the
      sample identity of >99% of singlets and identifies doublets at rates consistent
      with previous estimates. We apply demuxlet to assess cell-type-specific changes
      in gene expression in 8 pooled lupus patient samples treated with interferon
      (IFN)-beta and perform eQTL analysis on 23 pooled samples.

PMID- 29227471
TI  - Inhibiting mitochondrial phosphate transport as an unexploited antifungal
      strategy.
AB  - The development of effective antifungal therapeutics remains a formidable
      challenge because of the close evolutionary relationship between humans and
      fungi. Mitochondrial function may present an exploitable vulnerability because of
      its differential utilization in fungi and its pivotal roles in fungal
      morphogenesis, virulence, and drug resistance already demonstrated by others. We
      now report mechanistic characterization of ML316, a thiohydantoin that kills drug
      resistant Candida species at nanomolar concentrations through fungal-selective
      inhibition of the mitochondrial phosphate carrier Mir1. Using genetic,
      biochemical, and metabolomic approaches, we established ML316 as the first Mir1
      inhibitor. Inhibition of Mir1 by ML316 in respiring yeast diminished
      mitochondrial oxygen consumption, resulting in an unusual metabolic catastrophe
      marked by citrate accumulation and death. In a mouse model of azole-resistant
      oropharyngeal candidiasis, ML316 reduced fungal burden and enhanced azole
      activity. Targeting Mir1 could provide a new, much-needed therapeutic strategy to
      address the rapidly rising burden of drug-resistant fungal infection.

PMID- 29227472
TI  - Engineered synthetic scaffolds for organizing proteins within the bacterial
      cytoplasm.
AB  - We have developed a system for producing a supramolecular scaffold that permeates
      the entire Escherichia coli cytoplasm. This cytoscaffold is constructed from a
      three-component system comprising a bacterial microcompartment shell protein and
      two complementary de novo coiled-coil peptides. We show that other proteins can
      be targeted to this intracellular filamentous arrangement. Specifically, the
      enzymes pyruvate decarboxylase and alcohol dehydrogenase have been directed to
      the filaments, leading to enhanced ethanol production in these engineered
      bacterial cells compared to those that do not produce the scaffold. This is
      consistent with improved metabolic efficiency through enzyme colocation. Finally,
      the shell-protein scaffold can be directed to the inner membrane of the cell,
      demonstrating how synthetic cellular organization can be coupled with spatial
      optimization through in-cell protein design. The cytoscaffold has potential in
      the development of next-generation cell factories, wherein it could be used to
      organize enzyme pathways and metabolite transporters to enhance metabolic flux.

PMID- 29227473
TI  - Structure-inspired design of beta-arrestin-biased ligands for aminergic GPCRs.
AB  - Development of biased ligands targeting G protein-coupled receptors (GPCRs) is a
      promising approach for current drug discovery. Although structure-based drug
      design of biased agonists remains challenging even with an abundance of GPCR
      crystal structures, we present an approach for translating GPCR structural data
      into beta-arrestin-biased ligands for aminergic GPCRs. We identified specific
      amino acid-ligand contacts at transmembrane helix 5 (TM5) and extracellular loop
      2 (EL2) responsible for Gi/o and beta-arrestin signaling, respectively, and
      targeted those residues to develop biased ligands. For these ligands, we found
      that bias is conserved at other aminergic GPCRs that retain similar residues at
      TM5 and EL2. Our approach provides a template for generating arrestin-biased
      ligands by modifying predicted ligand interactions that block TM5 interactions
      and promote EL2 interactions. This strategy may facilitate the structure-guided
      design of arrestin-biased ligands at other GPCRs, including polypharmacological
      biased ligands.

PMID- 29227474
TI  - A proteolytic fragment of histone deacetylase 4 protects the heart from failure
      by regulating the hexosamine biosynthetic pathway.
AB  - The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4)
      regulates cardiac gene expression. Here we show that the levels of an N-terminal
      proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing
      mouse hearts than in healthy control hearts. Virus-mediated transfer of the
      portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected
      the heart from remodeling and failure; this was associated with decreased
      expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1
      dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely,
      exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific
      deletion of Hdac4 show reduced exercise capacity, which was characterized by
      cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that
      NR4A1 negatively regulated contractile function in a manner that depended on the
      HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in
      which epigenetic regulation of a metabolic pathway affects calcium handling.
      Activation of this axis during intermittent physiological stress promotes cardiac
      function, whereas its impairment in sustained pathological cardiac stress leads
      to heart failure.

PMID- 29227475
TI  - An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia
      reperfusion injury.
AB  - Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking
      effective therapy and validated pharmacological targets. Here, using integrative
      'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12
      hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31)
      signaling axis as a key determinant of the hepatic IR process. We found that
      ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE
      accumulation and that 12-HETE then directly binds to GPR31, triggering an
      inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE
      production inhibits IR-induced liver dysfunction, inflammation and cell death in
      mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model
      that closely recapitulates clinical liver dysfunction following liver resection.
      Most strikingly, blocking 12-HETE accumulation effectively attenuated all
      pathologies of hepatic IR in this model. Collectively, this study has revealed
      previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE
      GPR31 axis that functionally determines hepatic IR procession. We have also
      provided proof of concept that blocking 12-HETE production is a promising
      strategy for preventing and treating IR-induced liver damage.

PMID- 29227478
TI  - A potentiometric immunosensor for enterovirus 71 based on bis-MPA-COOH dendrimer
      doped AgCl nanospheres with a silver ion-selective electrode.
AB  - Herein a new potentiometric immunoassay for the point-of-care detection of
      enterovirus 71 (EV71) was developed by using a silver (Ag+) ion-selective
      electrode (ISE). Initially, the carboxylated dendrimer-doped AgCl nanospheres
      were synthesized by the reverse micelle method. Then the synthesized nanospheres
      were used to label a polyclonal mouse anti-EV71 antibody via a typical
      carbodiimide coupling method. The immunoreaction was executed on a monoclonal
      anti-EV71 antibody-coated microplate by using biofunctional AgCl nanospheres as
      the detection antibody. With a sandwich-type immunoassay format, the carried AgCl
      nanospheres could be dissolved in the presence of NH3.H2O, and the released
      silver ions were determined with an external silver ion-selective electrode.
      Under optimal conditions, the shift in the potential increased with the increase
      in the EV71 concentration, in a wide linear range of 0.3-300 ng mL-1, with a
      detection limit of 0.058 ng mL-1. Intra- and inter-assay relative standard
      deviations with identical batches were less than 4.15% and 6.15%, respectively.
      By validating the spiked serum samples, our system shows consistency with the
      enzyme-linked immunosorbent assay (ELISA) kit.

PMID- 29227479
TI  - Multiscale virtual particle based elastic network model (MVP-ENM) for normal mode
      analysis of large-sized biomolecules.
AB  - In this paper, a multiscale virtual particle based elastic network model (MVP
      ENM) is proposed for the normal mode analysis of large-sized biomolecules. The
      multiscale virtual particle (MVP) model is proposed for the discretization of
      biomolecular density data. With this model, large-sized biomolecular structures
      can be coarse-grained into virtual particles such that a balance between model
      accuracy and computational cost can be achieved. An elastic network is
      constructed by assuming "connections" between virtual particles. The connection
      is described by a special harmonic potential function, which considers the
      influence from both the mass distributions and distance relations of the virtual
      particles. Two independent models, i.e., the multiscale virtual particle based
      Gaussian network model (MVP-GNM) and the multiscale virtual particle based
      anisotropic network model (MVP-ANM), are proposed. It has been found that in the
      Debye-Waller factor (B-factor) prediction, the results from our MVP-GNM with a
      high resolution are as good as the ones from GNM. Even with low resolutions, our
      MVP-GNM can still capture the global behavior of the B-factor very well with
      mismatches predominantly from the regions with large B-factor values. Further, it
      has been demonstrated that the low-frequency eigenmodes from our MVP-ANM are
      highly consistent with the ones from ANM even with very low resolutions and a
      coarse grid. Finally, the great advantage of MVP-ANM model for large-sized
      biomolecules has been demonstrated by using two poliovirus virus structures. The
      paper ends with a conclusion.

PMID- 29227476
TI  - The molecular landscape of pediatric acute myeloid leukemia reveals recurrent
      structural alterations and age-specific mutational interactions.
AB  - We present the molecular landscape of pediatric acute myeloid leukemia (AML) and
      characterize nearly 1,000 participants in Children's Oncology Group (COG) AML
      trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed
      cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG
      methylation profiling. Validated DNA variants corresponded to diverse, infrequent
      mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic
      structural variants, including new gene fusions and focal deletions of MBNL1,
      ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared
      to adults. Conversely, mutations in DNMT3A and TP53, which were common in adults,
      were conspicuously absent from virtually all pediatric cases. New mutations in
      GATA2, FLT3 and CBL and recurrent mutations in MYC-ITD, NRAS, KRAS and WT1 were
      frequent in pediatric AML. Deletions, mutations and promoter DNA hypermethylation
      convergently impacted Wnt signaling, Polycomb repression, innate immune cell
      interactions and a cluster of zinc finger-encoding genes associated with KMT2A
      rearrangements. These results highlight the need for and facilitate the
      development of age-tailored targeted therapies for the treatment of pediatric
      AML.

PMID- 29227480
TI  - Elaborately programmed nanowires fabricated using a tapered push-pull nozzle
      system.
AB  - Elaborately programmed silver nanowire arrays can be prepared using a tapered
      push-pull nozzle system (TPPNS), which is used to directly write micro-nano wires
      on a substrate via a two-reagent reaction in the diffusion mixing region. The
      wires could be precisely positioned on the substrate and their width could be
      freely controlled from the micro to the nano scale, indicating an advance in the
      methodologies of controlling and fabricating nanowires. The as-prepared silver
      three-electrode device can serve as a three-electrode sensor.

PMID- 29227477
TI  - The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and
      ameliorates nonalcoholic steatohepatitis.
AB  - Activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key
      process in the progression of nonalcoholic steatohepatitis (NASH) and a promising
      target for treatment of the condition. However, the mechanism underlying ASK1
      activation is still unclear, and thus the endogenous regulators of this kinase
      remain open to be exploited as potential therapeutic targets. In screening for
      proteins that interact with ASK1 in the context of NASH, we identified the
      deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key
      endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly
      interacts with and deubiquitinates ASK1 in hepatocytes. Hepatocyte-specific
      ablation of Tnfaip3 exacerbated nonalcoholic fatty liver disease- and NASH
      related phenotypes in mice, including glucose metabolism disorders, lipid
      accumulation and enhanced inflammation, in an ASK1-dependent manner. In contrast,
      transgenic or adeno-associated virus-mediated TNFAIP3 gene delivery in the liver
      in both mouse and nonhuman primate models of NASH substantially blocked the onset
      and progression of the disease. These results implicate TNFAIP3 as a functionally
      important endogenous suppressor of ASK1 hyperactivation in the pathogenesis of
      NASH and identify it as a potential new molecular target for NASH therapy.

PMID- 29227481
TI  - Nafion particles doped with methyl viologen: electrochemistry.
AB  - Nafion sub-micro particles doped with methyl viologen (MV2+) are synthesized
      using the re-precipitation method and characterized by scanning electron
      microscopy and UV-Vis spectroscopy. The electrochemical behavior of MV2+
      incorporated into Nafion particles was investigated at both the ensemble and
      single particle levels. The charge transferred to single MV-Nafion particles was
      observed using the nano-impact method and shown to be quantitative. Finally, the
      charge transferred via individual MV-Nafion particle was substantially enhanced
      in the presence of permanganate. The mechanism of the catalytic nano-impact
      reaction of mediated permanganate reduction by single MV-Nafion particle is
      revealed as proceeding via MV+ reduced from MV2+ incorporated in Nafion particles
      through one electron transfer followed by the reduction of permanganate.

PMID- 29227482
TI  - Direct characterization of graphene doping state by in situ photoemission
      spectroscopy with Ar gas cluster ion beam sputtering.
AB  - On the basis of an in situ photoemission spectroscopy (PES) system, we propose a
      novel, direct diagnosis method for the characterization of graphene (Gr) doping
      states at organic semiconductor (OSC)/electrode interfaces. Our in situ PES
      system enables ultraviolet/X-ray photoelectron spectroscopy (UPS/XPS)
      measurements during the OSC growth or removal process. We directly deposit C60
      films on three different p-type dopants-gold chloride (AuCl3), (trifluoromethyl
      sulfonyl)imide (TFSI), and nitric acid (HNO3). We periodically characterize the
      chemical/electronic state changes of the C60/Gr structures during their aging
      processes under ambient conditions. Depositing the OSC on the p-type doped Gr
      also prevents severe degradation of the electrical properties, with almost
      negligible transition over one month, while the p-type doped Gr without an OSC
      changes a lot following one month of aging. Our results indicate that the
      chemical/electronic structures of the Gr layer are completely reflected in the
      energy level alignments at the C60/Gr interfaces. Therefore, we strongly believe
      that the variation of energy level alignments at the OSC/graphene interface is a
      key standard for determining the doping state of graphene after a certain period
      of aging.

PMID- 29227485
TI  - Solid-liquid equilibria for a pyrrolidinium-based common-cation ternary ionic
      liquid system, and for a pyridinium-based ternary reciprocal ionic liquid system:
      an experimental study and a thermodynamic model.
AB  - The present paper describes an experimental study and a thermodynamic model for
      the phase diagrams of the common-cation ternary system [C4MPyrr]Cl-[C4MPyrr]Br
      [C4MPyrr]BF4 (where [C4MPyrr] refers to 1-butyl-1-methyl-pyrrolidinium) and of
      the ternary reciprocal system [C2Py], [C4Py]||Cl, Br (where [CnPy] refers to 1
      alkyl-pyridinium). Phase equilibria were measured by Differential Scanning
      Calorimetry (DSC) for two isoplethal sections in the common-cation pyrrolidinium
      based ternary system. Phase diagram measurements were recently performed for the
      four common-ion binary subsystems and the two diagonal sections in the pyridinium
      based ternary reciprocal system. In each case, the Modified Quasichemical Model
      was used to model the liquid solution, and the Compound Energy Formalism was used
      for the relevant solid solutions. For the ternary reciprocal system, the missing
      thermodynamic properties of the pure compounds were assessed using the Volume
      based Thermodynamics (VBT) from Glasser and Jenkins, making it possible to
      estimate the exchange Gibbs free energy for the reaction [C2Py]Br (liquid) +
      [C4Py]Cl (liquid) = [C2Py]Cl (liquid) + [C4Py]Br (liquid). The experimental
      diagonal sections [C4Py]Br-[C2Py]Cl and [C4Py]Cl-[C2Py]Br were satisfactorily
      reproduced using solely the optimized model parameters for the four common-ion
      binary subsystems.

PMID- 29227487
TI  - Hairpin loop-enhanced fluorescent copper nanoclusters and application in S1
      nuclease detection.
AB  - Novel highly fluorescent copper nanoclusters (CuNCs) were prepared by using 24
      adenine-thymine pair dsDNA (AT24) with six-base (X6) loops (AT24-X6-hairpin DNA)
      as an effective template. The AT24 double strand stem serves as a template for
      CuNC formation, and the six-base sequence loop acts as specific regions to
      enhance the fluorescence intensity of CuNCs. Relative to the AT24-CuNCs, AT24-X6
      hairpin CuNCs have greater fluorescence (5 times enhancement). What's more, the
      influence of the hairpin loop with different base types and base numbers on the
      fluorescence of CuNCs was first proposed and investigated. By choosing an AT24
      double strand stem, any types of base loops can enhance the fluorescence of
      CuNCs. However, the fluorescence enhancement would be reduced with an increasing
      number of hairpin loop sequences. Besides this, the successful detection of S1
      nuclease demonstrates its potential to be a new and robust fluorescent probe for
      sensing applications.

PMID- 29227488
TI  - Physico-chemical profiles of the wobble <-> Watson-Crick G*.2AP(w) <-> G.2AP(WC)
      and A.2AP(w) <-> A*.2AP(WC) tautomerisations: a QM/QTAIM comprehensive survey.
AB  - This study is intended to clarify in detail the tautomeric transformations of the
      wobble (w) G*.2AP(w) and A.2AP(w) nucleobase mispairs involving 2-aminopurine
      (2AP) into the Watson-Crick (WC) G.2AP(WC) and A*.2AP(WC) base mispairs
      (asterisks denote mutagenic tautomers of the DNA bases), respectively, by quantum
      mechanical methods and Bader's Quantum Theory of Atoms in Molecules. Our
      previously reported methodology has been used, which allows the evolution of the
      physico-chemical parameters to be tracked along the entire internal reaction
      coordinate (IRC), not exclusively in the stationary states of these reactions.
      These biologically important G*.2AP(w) <-> G.2AP(WC) and A.2AP(w) <-> A*.2AP(WC)
      w <-> WC tautomerisations, which are involved in mutagenic tautomerically
      conformational pathways, determine the origin of the transitions and
      transversions induced by 2AP. In addition, it is established that they proceed
      through planar, highly stable, zwitterionic transition states and they exhibit
      similar physico-chemical profiles and stages of sequential intrapair proton
      transfer, followed by spatial rearrangement of the nucleobases relative to each
      other within the base pairs. These w <-> WC tautomerisations occur non
      dissociatively and are accompanied by a significant alteration in geometry (from
      wobble to Watson-Crick and vice versa) and redistribution of the specific
      intermolecular interactions, which can be divided into 10 patterns including AHB
      H-bonds and loosened A-H-B covalent bridges along the IRC of tautomerisation.
      Based on the redistribution of the geometrical and electron-topological
      parameters of the intrapair hydrogen bonds, exactly 9 key points have been
      allocated to characterize the evolution of these reactions.

PMID- 29227489
TI  - Synergism and aggregation behaviour in an aqueous binary mixture of cationic
      zwitterionic surfactants: physico-chemical characterization with molecular
      simulation approach.
AB  - Aqueous interactions between a cationic surfactant benzyl
      dimethylhexadecylammonium chloride (BDHAC) and alkyldimethylammoniopropane
      sulfonates (CnDAPS) based three zwitterionic surfactants n = 10, 12, and 14
      (abbreviated as C10DAPS, C12DAPS and C14DAPS, respectively) were studied using
      tensiometry, and fluorescence spectrophotometry techniques. The critical micelle
      concentration degree of synergism and various other parameters such as
      interaction parameter (beta), activity coefficients (fm) and interfacial
      parameters such as surface pressure (piCMC), packing parameter (P), surface
      excess concentration (Gammamax), surface tension at CMC (gammaCMC), and minimum
      area per molecule (Amin) were evaluated using the Regular Solution Theory (RST)
      of mixed systems. The results indicate a strong dependency on the mixed system
      and their composition. For the quantitative prediction, the molecular
      architecture of the surfactants in mixed systems and their synergistic
      interactions were investigated by computational simulation using Spartan'14
      V1.1.8. The structural optimization results obtained were found to be in good
      agreement with the estimations made using RST. The reduction in surface tension
      indicates a certain efficiency in mixed micelle formation owing to electrostatic
      attraction between the cationic and zwitterionic surfactants. In addition, the
      binary surfactant systems evaluated by Maeda's approach infer the mixed micelles
      are thermodynamically stable. The aggregation number (Nagg) appeared to be larger
      at the composition point where the efficiency of mixed micelle formation is
      greatest. The strength of the interaction between BDHAC and CnDAPS followed the
      order: C14DAPS > C12DAPS > C10DAPS indicating a greater synergism at 0.25 molar
      ratio of zwitterionic surfactants to cationic surfactants in the aqueous solution
      at 303.15 K.

PMID- 29227490
TI  - The role of PbI2 in CH3NH3PbI3 perovskite stability, solar cell parameters and
      device degradation.
AB  - We report a systematic investigation on the role of excess PbI2 content in
      CH3NH3PbI3 perovskite film properties, solar cell parameters and device storage
      stability. We used the CH3NH3I vapor assisted method for the preparation of PbI2
      free CH3NH3PbI3 films under a N2 atmosphere. These pristine CH3NH3PbI3 films were
      annealed at 165  degrees C for different time intervals in a N2 atmosphere to
      generate additional PbI2 in these films. From XRD measurements, the excess of
      PbI2 was quantified. Detailed characterization using scanning electron
      microscopy, X-ray diffraction, UV-Visible and photoluminescence for continuous
      aging of CH3NH3PbI3 films under ambient condition (50% humidity) is carried out
      for understanding the influence of different PbI2 contents on degradation of the
      CH3NH3PbI3 films. We find that the rate of degradation of CH3NH3PbI3 is
      accelerated due to the amount of PbI2 present in the film. A comparison of solar
      cell parameters of devices prepared using CH3NH3PbI3 samples having different
      PbI2 contents reveals a strong influence on the current density-voltage
      hysteresis as well as storage stability. We demonstrate that CH3NH3PbI3 devices
      do not require any residual PbI2 for a high performance. Moreover, a small amount
      of excess PbI2, which improves the initial performance of the devices slightly,
      has undesirable effects on the CH3NH3PbI3 film stability as well as on device
      hysteresis and stability.

PMID- 29227492
TI  - Impact of complex surfaces on biomicrorheological measurements using optical
      tweezers.
AB  - The characterisation of physical properties in biologically relevant processes
      and the development of novel microfluidic devices for this purpose are
      experiencing a great resurgence at present. In many of measurements of this type
      where a probe in a fluid is used, the strong influence of the boundaries of the
      volume used is a serious problem. In these geometries the proximity of a probe to
      a wall can severely influence the measurement. However, although much knowledge
      has been gained about flat walls, to date, the effect of non-planar surfaces at
      microscopic scale on rotational motion of micro-objects has not been studied.
      Here we present for the first time both experimental measurements and numerical
      computations which aim to study the drag torque on optically trapped rotating
      particles moving near 3D-printed conical and cylindrical walls on-chip. These
      results are essential for quantifying how curved walls can effect the torque on
      particles, and thus enable accurate hydrodynamic simulations at the micron-scale.
      This opens the potential for new sensing approaches under more complex
      conditions, allowing both dynamic and microrheological studies of biological
      systems and lab-on-chip devices.

PMID- 29227493
TI  - Prophylactic role of vitamin K supplementation on vascular inflammation in type 2
      diabetes by regulating the NF-kappaB/Nrf2 pathway via activating Gla proteins.
AB  - There is no previous study that has examined the relationship between circulating
      vitamin K1 (VK1) and vascular inflammation in type 2 diabetes (T2D). This study
      aims to examine the hypothesis that circulating VK1 deficiency may be associated
      with higher inflammation and insulin resistance in T2D patients and that VK1
      supplementation regulates the NF-kappaB/Nrf2 pathway via activating VK-dependent
      Gla proteins and reduces vascular inflammation. The results showed that plasma
      VK1 levels were significantly lower and MCP-1, fasting glucose, HbA1c, and
      insulin resistance (HOMA-IR) were significantly higher in T2D patients compared
      to those in the controls. The lower levels of VK1 in T2D patients were
      significantly and inversely correlated with MCP-1 and HOMA-IR, which suggests
      that VK1 supplementation may reduce the vascular inflammation and insulin
      resistance in T2D. Using a high fat diet-fed T2D mice model this study further
      demonstrated that VK1 supplementation (1, 3, 5 MUg per kg BW, 8 weeks) dose
      dependently decreased the body weight gain, glucose intolerance, fasting glucose,
      glycated hemoglobin, HOMA-IR, and cytokine secretion (MCP-1 and IL-6) in T2D
      mice. Further cell culture studies showed that VK1 supplementation (1, 5, or 10
      nM) decreased NF-kappaB phosphorylation and MCP-1 secretion and increased Nrf2
      protein expression in high glucose (HG, 25 mM)-treated monocytes. Signal
      silencing studies with GGCX siRNA again depicted the role of VK-dependent Gla
      proteins in mediating the effect of VK1 on vascular inflammation in HG-treated
      cells. In conclusion, this study suggests that circulating VK1 has a positive
      effect in lowering vascular inflammation in T2D by regulating NF-kappaB/Nrf2
      transcription factors via activating VK-dependent Gla proteins.

PMID- 29227494
TI  - The crucial role of a spacer material on the efficiency of charge transfer
      processes in organic donor-acceptor junction solar cells.
AB  - Organic photovoltaic donor-acceptor junction devices composed of pi-conjugated
      polymer electron donors (D) and fullerene electron acceptors (A) show greatly
      increased performance when a spacer material is inserted between the two layers
      (W. Y. Nie, G. Gupta, B. K. Crone, F. L. Liu, D. L. Smith, P. P. Ruden, C. Y.
      Kuo, H. Tsai, H. L. Wang, H. Li, S. Tretiak and A. D. Mohite, Adv. Sci., 2015, 2,
      1500024.). For instance, experimental results reveal significant improvement of
      photocurrent when a terthiophene oligomer derivative is inserted in between pi
      conjugated poly(3-hexylthiophene-2,5-diyl) (P3HT) donor and C60 acceptor. These
      results indicate favorable charge separation dynamics, which is addressed by our
      present joint theoretical/experimental study establishing the beneficial
      alignment of electronic levels due to the specific morphology of the material.
      Namely, based on the experimental data we have constructed extended structural
      interface models containing C60 fullerenes and P3HT separated by aligned oligomer
      chains. Our time-dependent density functional theory (TD-DFT) calculations based
      on a long-range corrected functional, allowed us to address the energetics of
      essential electronic states and analyze them in terms of charge transfer (CT)
      character. Specifically, the simulations reveal the electronic spectra composed
      of a ladder of excited states evolving excitation toward spatial charge
      separation: an initial excitonic excitation at P3HT decomposes into charges by
      sequentially relaxing through bands of C60-centric, oligomer -> C60 and P3HT ->
      C60 CT states. Our modeling exposes a critical role of dielectric environment
      effects and electronic couplings in the self-assembled spacer oligomer layer on
      the energetics of critical CT states leading to a reduced back-electron transfer,
      preventing recombination losses, and thus rationalizes physical processes
      underpinning experimental observations.

PMID- 29227495
TI  - Fluorescence-activated droplet sorting of lipolytic microorganisms using a
      compact optical system.
AB  - Lipases are ubiquitous enzymes of great physiological significance that have been
      used extensively in multiple industries. Environmental microorganisms are a major
      source for the discovery of novel lipases with high catalytic efficiency and
      selectivity. However, current plate-based screening of lipase-producing strains
      is time consuming, labour intensive and inefficient. In this study, we developed
      an ultra-high throughput screening pipeline for lipase-producing strains based on
      fluorescence-activated droplet sorting (FADS) using a compact optical system that
      could be easily set up in an alignment-free manner. The pipeline includes droplet
      generation, droplet incubation, picoinjection of the fluorescence probe, and
      sorting of droplets with a throughput of 2 * 106 drops per h. We applied the
      pipeline to screen samples collected from different locations, including
      sediments from a hot spring in Tibet, soils from the Zoige wetland, contaminated
      soils from an abandoned oilfield, and a Chinese Daqu starter. In total, we
      obtained 47 lipase-producing bacterial strains belonging to seven genera,
      including Staphylococcus, Bacillus, Enterobacter, Serratia, Prolinoborus,
      Acinetobacter, and Leclercia. We believe that this FADS-based pipeline could be
      extended to screen various enzymes from the environment, and may find wide
      applications in breeding of industrial microorganisms.

PMID- 29227496
TI  - Pyrazole synthesis via a cascade Sonogashira coupling/cyclization of N-propargyl
      sulfonylhydrazones.
AB  - An efficient approach for the preparation of pyrazoles via a Pd(ii)/Cu(i)
      catalyzed Sonogashira coupling/cyclization of N-propargyl sulfonylhydrazones has
      been established. In this study, we firstly report the strategic use of a
      Sonogashira reaction to construct pyrazole rings in a one step operation. With a
      broad range of functional group tolerance, bioactive 3-CF3 pyrazoles can also be
      synthesized easily through this domino coupling/cyclization sequence.

PMID- 29227498
TI  - Elastic particle deformation in rectangular channel flow as a measure of particle
      stiffness.
AB  - In this study, we experimentally observed and characterized soft elastic particle
      deformation in confined flow in a microchannel with a rectangular cross-section.
      Hydrogel microparticles of pNIPAM were produced using two different
      concentrations of crosslinker. This resulted in particles with two different
      shear moduli of 13.3 +/- 5.5 Pa and 32.5 +/- 15.7 Pa and compressive moduli of 66
      +/- 10 Pa and 79 +/- 15 Pa, respectively, as measured by capillary
      micromechanics. Under flow, the particle shapes transitioned from circular to
      egg, triangular, arrowhead, and ultimately parachute shaped with increasing shear
      rate. The shape changes were reversible, and deformed particles relaxed back to
      circular/spherical in the absence of flow. The thresholds for each shape
      transition were quantified using a non-dimensional radius of curvature at the
      tip, particle deformation, circularity, and the depth of the concave dimple at
      the trailing edge. Several of the observed shapes were distinct from those
      previously reported in the literature for vesicles and capsules; the elastic
      particles had a narrower leading tip and a lower circularity. Due to variations
      in the shear moduli between particles within a batch of particles, each flow rate
      corresponded to a small but finite range of capillary number (Ca) and resulted in
      a series of shapes. By arranging the images on a plot of Ca versus circularity, a
      direct correlation was developed between shape and Ca and thus between particle
      deformation and shear modulus. As the shape was very sensitive to differences in
      shear modulus, particle deformation in confined flow may allow for better
      differentiation of microparticle shear modulus than other methods.

PMID- 29227497
TI  - Dietary fruits and arthritis.
AB  - Arthritis is a global health concern affecting a significant proportion of the
      population and associated with reduced quality of life. Among the different forms
      of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most
      common and lacking a definite cure in the affected individuals. Fruits, such as
      berries and pomegranates are rich sources of a variety of dietary bioactive
      compounds, especially the polyphenolic flavonoids that have been associated with
      antioxidant, anti-inflammatory and analgesic effects. Emerging research
      demonstrates a protective role of fruits and their polyphenols in pre-clinical,
      clinical and epidemiological studies of OA and RA. In this context, commonly
      available fruits, such as blueberries, raspberries and strawberries, and
      pomegranates have shown promising results in reducing pain and inflammation in
      experimental models and in human clinical studies of arthritis. There is also
      some evidence on the role of specific fruit polyphenols, such as quercetin and
      citrus flavonoids in alleviating RA symptoms. These emerging data deserve further
      investigation in rigorous scientific studies to determine the mechanisms, dosing
      and selection of fruits and fruit extracts in arthritis management.

PMID- 29227499
TI  - Self-discriminating fluorescent hybrid nanocrystals: efficient and accurate
      tracking of translocation via oral delivery.
AB  - The in vivo fate of nanocrystals is a controversial topic, i.e. dissolving versus
      integral absorption through the intestinal membrane. This is due to the lack of
      functional strategies to identify integral nanocrystals. In this study, the in
      vivo fate of quercetin hybrid nanocrystals (QT-HNCs) via the oral route is
      explored by physically embedding an environment-responsive probe in the crystal
      lattices of quercetin. The specific property of the probe is the water-initiated
      aggregation-caused quenching (ACQ) ability, by which integral QT-HNCs can be self
      discriminated. Instead of dissolving instantly, QT-HNCs can be retained in the
      gastrointestinal tract for 12-16 h, and can then be absorbed and distributed into
      various organs with the liver as the primary terminal. The ileum provides better
      absorption than the jejunum. Cellular studies prove that both trans-epithelial
      and M cell-mediated routes are involved in the absorption of integral QT-HNCs,
      which may be impeded by the mucous layer. Moreover, the particle size affects the
      in vivo behavior and the ex vivo cellular interaction of QT-HNCs, with moderate
      size, such as 550 nm, being preferred. The results not only validate the idea of
      using ACQ fluorophores for bioimaging of integral nanocrystals but also support
      the intestinal absorption of nanocrystals.

PMID- 29227500
TI  - Enhanced topical delivery of dexamethasone by beta-cyclodextrin decorated
      thermoresponsive nanogels.
AB  - Highly hydrophilic, responsive nanogels are attractive as potential systems for
      the topical delivery of bioactives encapsulated in their three-dimensional
      polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for
      efficient delivery of hydrophobic drugs. Addressing this, beta-cyclodextrin
      (betaCD) could be successfully introduced into the drug carrier systems by
      exploiting its unique affinity toward dexamethasone (DXM) as well as its role as
      topical penetration enhancer. The properties of betaCD could be combined with
      those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG)
      as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing
      responsiveness to temperature changes. Electron paramagnetic resonance (EPR)
      studies localized the drug within the hydrophobic cavity of betaCD by differences
      in its mobility and environmental polarity. In fact, the fabricated carriers
      combining a particulate delivery system with a conventional penetration enhancer,
      resulted in an efficient delivery of DXM to the epidermis and the dermis of human
      skin ex vivo (enhancement compared to commercial DXM cream: ~2.5 fold in
      epidermis, ~30 fold in dermis). Furthermore, DXM encapsulated in betaCD tNGs
      applied to skin equivalents downregulated the expression of proinflammatory
      thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM
      cream.

PMID- 29227501
TI  - Chondrogenic potential of macroporous biodegradable cryogels based on synthetic
      poly(alpha-amino acids).
AB  - In this study, the potential of highly porous hydrogels based on biodegradable
      synthetic poly(alpha-amino acids) to support proliferation and chondrogenesis of
      human dental pulp stem cells (hDPSCs) was investigated. Covalently crosslinked
      gels with permanent pores were formed under cryogenic conditions by free-radical
      copolymerization of poly[N5-(2-hydroxyethyl)-l-glutamine-stat-N5-(2-methacryloyl
      oxy-ethyl)-l-glutamine] (PHEG-MA) with 2-hydroxyethyl methacrylate (HEMA) and N
      propargyl methacrylamide (PrMAAm) as minor co-monomers. PrMAAm provided alkyne
      groups for modifying the gels with cell-supporting moieties (RGDS peptides) by
      the azide-alkyne "click"-reaction. Two types of gels with different compressive
      moduli were prepared. Each type was modified with two different concentrations of
      RGDS peptide. X-ray computed nanotomography (nanoCT) was used to visualize and
      analyze the 3D-structure of the cryogels. It was shown that modifying the PHEG-MA
      cryogels within the range of RGDS concentrations examined here had a positive
      effect on the proliferation of hDPSCs. Immunofluorescence staining for collagen
      type 2 and aggrecan proved that there was differentiation of hDPSCs into
      chondrocytes.

PMID- 29227502
TI  - Sensing in-plane nanomechanical surface and sub-surface properties of polymers:
      local shear stress as function of the indentation depth.
AB  - Dynamic force microscopy (DFM) is an excellent tool for the study of the
      compositional and nanomechanical properties of polymers that exploits the
      flexural eigenmodes of a cantilever comprising a sharp tip vibrating
      perpendicular to the sample surface. However, the in-plane nanomechanical
      properties of a specimen cannot be detected by this technique. Here, a bimodal
      approach was developed where flexural and torsional eigenmodes are driven
      simultaneously. The corresponding vibrational amplitude and phase shift of the
      vertical tip motion were utilized for topographical feedback and out-of-plane
      dissipative interaction acquisition, respectively, whereas the frequency shift
      and the drive amplitude of the lateral tip motion mapped the in-plane
      conservative and dissipative interactions of two heterogeneous polymers: an
      elastomeric polypropylene (ePP) and a polystyrene-block-polybutadiene diblock
      copolymer (SB). The shear stress at different sub-surface levels revealed an
      amorphous cover layer as well as a "slipping" plane on the ePP crystallites. The
      imaging of SB supported by dynamic force spectroscopy experiments showed that SB
      exhibits considerably different in- and out-of-plane nanomechanical properties at
      certain areas due to the complex polymer conformation of this diblock copolymer
      accompanied by inter- and intramolecular interactions that give rise to its
      viscoelastic behavior.

PMID- 29227504
TI  - X-ray crystal structure and doping mechanism of bimetallic nanocluster Au36
      xCux(m-MBT)24 (x = 1-3).
AB  - A novel Au36-xCux(m-MBT)24 (x = 1-3, m-MBT = 3-methylbenzenethiolate) nanocluster
      has been prepared. According to the X-ray single crystal diffractometer, the
      structure of Au36-xCux(m-MBT)24 is similar to that of Au36(SPhtBu)24. The Au36
      xCux(m-MBT)24 nanocluster contains a face-centered cubic (FCC) M28 core, which is
      protected by 4 M2S3 (M = Au/Cu) staple motifs and 12 bridging SR ligands. The Cu
      dopants could possibly occupy 14 sites (six in the sub-surface and eight in the
      staple motifs). Spectral monitoring indicates that the number of Cu dopants
      sequentially increased on increasing the amount of Cu precursors (relative to a
      Au control). Meanwhile, DFT calculations imply that the maximum doping number of
      Cu is 3, and doping occurs preferentially at the staple sites and sub-surface
      sites (instead of the centre of the core). Because the atomic orbital of the
      peripheral locations hardly contributes to the frontier molecular orbitals, the
      UV-vis of the AuCu alloy is almost the same as that of its homometallic Au
      counterpart.

PMID- 29227505
TI  - Neurobiology of Sexual Assault and Osteopathic Considerations for Trauma-Informed
      Care and Practice.
AB  - Sexual assault is a traumatic event with potentially devastating lifelong effects
      on physical and emotional health. Sexual assault is associated with
      gastrointestinal, neurologic, and reproductive symptoms, as well as obesity,
      diabetes, and chronic pain. With 1 in 3 women and 1 in 6 men experiencing some
      form of unwanted sexual violence in their lifetime, sexual assault is a
      significant public health problem that necessitates attention in the medical
      community. This review discusses relevant literature on the neurobiologic changes
      that occur as a consequence of sexual assault, such as how the brain responds
      during a traumatic experience and the impact of trauma on memory. Osteopathic
      considerations for trauma-informed care and practice and how all physicians can
      better serve patients with a history of sexual assault are also discussed.

PMID- 29227507
TI  - The Use of Capsular Tension Rings to Reduce Refractive Shift in Patients With
      Implantation of Trifocal Intraocular Lenses.
AB  - PURPOSE: To determine whether use of a capsular tension ring (CTR) can increase
      refractive stability in patients with implantation of two different trifocal
      intraocular lenses (IOLs). METHODS: A prospective, consecutive series of eyes
      underwent refractive lens exchange with implantation of two different trifocal
      IOL designs: FineVision Micro F (non-toric) and FineVision POD FT (toric)
      (PhysIOL, Liege, Belgium). Power calculation was determined using the Haigis
      formula. Refractive lens exchange surgery was performed according to the standard
      Memira protocol. Refractive results and stability were assessed at 2 weeks and 3
      months postoperatively. RESULTS: Three hundred eighty-eight eyes were included in
      the analysis. Overall, 71% and 76% of MicroF eyes implanted with (n = 139) and
      without (n = 104) a CTR, respectively, had hyperopic shift; 9% of MicroF eyes
      with a CTR had a shift of greater than +0.50 to +0.75 or less diopters (D) and 4%
      had a shift of greater than +0.75 D. In MicroF eyes without a CTR, 12% and 3% of
      eyes experienced a refractive shift of greater than +0.50 to +0.75 D or less and
      greater than +0.75 D, respectively. In the POD FT group, 72% and 69% of eyes with
      (n = 81) and without (n = 64) a CTR, respectively, had hyperopic shift; 10% of
      POD FT eyes with a CTR had a change of greater than +0.50 to +0.75 D or less and
      7% had a shift of greater than +0.75 D. In POD FT eyes without a CTR, 13% and 3%
      experienced a refractive shift of greater than +0.50 to +0.75 D or less and
      greater than +0.75 D, respectively. For the MicroF design, the best refractive
      stability was found in the CTR group and the poorest stability in the non-CTR
      group (P = .084). For the POD FT design, the best refractive stability was found
      in the non-CTR group and the poorest stability in the CTR group (P = .297).
      CONCLUSIONS: Up to 7% of eyes implanted with FineVision trifocal IOLs had a
      hyperopic shift of greater than +0.75 D approximately 2 weeks to 3 months
      postoperatively. Using a CTR in MicroF eyes had no statistically significant
      effect on refractive stability. Placing a CTR with POD FT IOLs appeared to reduce
      refractive stability, although not significantly. [J Refract Surg.
      2017;33(12):802-806.].

PMID- 29227506
TI  - Comparison of Methodologies Using Estimated or Measured Values of Total Corneal
      Astigmatism for Toric Intraocular Lens Power Calculation.
AB  - PURPOSE: To compare the prediction error in the calculation of toric intraocular
      lenses (IOLs) associated with methods that estimate the power of the posterior
      corneal surface (ie, Barrett toric calculator and Abulafia-Koch formula) with
      that of methods that consider real measures obtained using Scheimpflug imaging: a
      software that uses vectorial calculation (Panacea toric calculator:
      http://www.panaceaiolandtoriccalculator.com) and a ray tracing software
      (PhacoOptics, Aarhus Nord, Denmark). METHODS: In 107 eyes of 107 patients
      undergoing cataract surgery with toric IOL implantation (Acrysof IQ Toric; Alcon
      Laboratories, Inc., Fort Worth, TX), predicted residual astigmatism by each
      calculation method was compared with manifest refractive astigmatism. Prediction
      error in residual astigmatism was calculated using vector analysis. RESULTS: All
      calculation methods resulted in overcorrection of with-the-rule astigmatism and
      undercorrection of against-the-rule astigmatism. Both estimation methods resulted
      in lower mean and centroid astigmatic prediction errors, and a larger number of
      eyes within 0.50 diopters (D) of absolute prediction error than methods
      considering real measures (P < .001). Centroid prediction error (CPE) was 0.07 D
      at 172 degrees  for the Barrett toric calculator and 0.13 D at 174 degrees  for
      the Abulafia-Koch formula (combined with Holladay calculator). For methods using
      real posterior corneal surface measurements, CPE was 0.25 D at 173 degrees  for
      the Panacea calculator and 0.29 D at 171 degrees  for the ray tracing software.
      CONCLUSIONS: The Barrett toric calculator and Abulafia-Koch formula yielded the
      lowest astigmatic prediction errors. Directly evaluating total corneal power for
      toric IOL calculation was not superior to estimating it. [J Refract Surg.
      2017;33(12):794-800.].

PMID- 29227508
TI  - Laboratory Evaluation of the Influence of Decentration and Pupil Size on the
      Optical Performance of a Monofocal, Bifocal, and Trifocal Intraocular Lens.
AB  - PURPOSE: To assess the influence of decentration and aperture size on the optical
      quality of different intraocular lenses (IOLs) of the same material, body design,
      and refractive power using standardized optical bench testing. METHODS: Using an
      optical bench set-up, an aspheric monofocal (CT ASPHINA 409M; Carl Zeiss Meditec,
      Jena, Germany), an aspheric diffractive bifocal (AT LISA 809M; Carl Zeiss
      Meditec), and an aspheric diffractive trifocal (AT LISA 839M; Carl Zeiss Meditec)
      intraocular lens (IOL) were evaluated, each with the same distance power, body
      design, and material. Modulation transfer function (MTF) values were measured at
      spatial frequencies of 50 lp/mm and aperture sizes of 3 and 4.5 mm. Each IOL was
      measured while centered, then decentered by 0.25, 0.5, 0.75, and 1 mm. RESULTS:
      MTF values for the monofocal IOL at far focus with 3- and 4.5-mm aperture size
      were 0.80/0.80 with maximum reduction to 0.77/0.73 for 1-mm decentration,
      respectively. Centered IOL MTFs of the bifocal and trifocal IOLs were lower for
      the far focus at 0.46/0.41 and 0.39/0.26, with reduction at 1-mm decentration to
      0.35/0.25 and 0.25/0.18, respectively. Values for near focus of the bifocal and
      trifocal IOLs reduced from 0.27/0.31 and 0.19/0.18 to 0.2/0.21 and 0.12/0.13,
      respectively. The trifocal intermediate focus MTF reduced from 0.15/0.10 to
      0.12/0.08. MTF values of all three lenses decreased significantly under all
      conditions with decentration of 0.5 to 0.75 mm. CONCLUSIONS: Monofocal lenses
      were least negatively affected by decentration, with mean optical quality
      reduction of less than 10% for 1-mm decentration at physiological pupil sizes.
      For diffractive bifocal and trifocal lenses, optical quality at all distances was
      significantly reduced if decentration exceeded 0.75 mm, with intermediate focus
      showing the least reduction. [J Refract Surg. 2017;33(12):808-812.].

PMID- 29227509
TI  - Long-term Follow-up of LASEK With Mitomycin C Performed to Correct Myopia in Thin
      Corneas.
AB  - PURPOSE: To evaluate the long-term outcomes of laser-assisted subepithelial
      keratomileusis (LASEK) with intraoperative use of mitomycin C (MMC) performed on
      thin corneas for the correction of myopia. METHODS: This retrospective cohort
      study included 100 eyes with a preoperative central corneal thickness (CCT)
      thinner than 500 MUm that underwent LASEK + MMC with at least 6 years of follow
      up. Stability of visual acuity and refraction and the efficacy, safety, and
      predictability at the examinations 3 months and the last annual postoperative
      visit were analyzed. RESULTS: Preoperative CCT was 482.9 +/- 14.7 MUm (range: 433
      to 499 MUm). Mean preoperative spherical equivalent was -4.09 +/- 2.3 diopters
      (D). At the 3-month postoperative visit, mean CCT was 419.79 +/- 32.6 MUm. The
      residual spherical equivalent showed a statistically significant regression (P =
      .001) in the comparison between the 3-month and the last annual postoperative
      visit. The efficacy index showed a significant decrease (P = .01) and the safety
      index remained stable around 0.96. Six or more years after the surgery, 85 eyes
      (85%) were within +/-0.50 D and 94 eyes (94%) eyes were within +/-1.00 D of
      emmetropia. The topography did not show signs of secondary corneal ectasia in any
      eye. CONCLUSIONS: LASEK with intraoperative use of MMC seems to be safe,
      effective, and predictable to correct myopia in corneas thinner than 500 MUm and
      with normal preoperative topography, providing good visual and refractive
      outcomes with no topographic signs of corneal ectasia in a mean 6.5-year follow
      up. [J Refract Surg. 2017;33(12):813-819.].

PMID- 29227510
TI  - Postoperative Corneal Asphericity in Low, Moderate, and High Myopic Eyes After
      Transepithelial PRK Using a New Pulse Allocation.
AB  - PURPOSE: To evaluate the postoperative asphericity in low, moderate, and high
      myopic eyes after combined transepithelial photorefractive keratectomy and
      SmartSurfACE treatment (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany).
      METHODS: In this retrospective case series, the outcomes of myopic SmartSurfACE
      were evaluated at 3 months postoperatively in 106 eyes and divided into low (less
      than -4.125 diopters [D]), moderate (-4.125 to -6.25 D), and high (more than 
      6.25 D) myopia groups. In all cases, standard examinations and preoperative and
      postoperative corneal topography (SCHWIND Sirius) were performed. The analysis
      comprised evaluating the change in asphericity versus planned correction,
      comparing expected and achieved postoperative asphericity for all eyes, and
      comparison of the three groups in terms of the preoperative and postoperatively
      expected and achieved asphericity. RESULTS At 3 months postoperatively, the low
      myopia group (n = 33) improved average negative asphericity (Q = -0.04 +/- 0.17
      preoperative vs -0.19 +/- 0.20 postoperative, P < .05). The moderate myopia group
      (n = 35) maintained or slightly improved average negative asphericity (Q = -0.07
      +/- 0.14 preoperative vs -0.05 +/- 0.24 postoperative, P = .35). For the high
      myopia group (n = 38), the eyes became more oblate compared to the preoperative
      status (Q = -0.09 +/- 0.15 preoperative vs 0.62 +/- 0.70 postoperative, P < .05).
      In terms of asphericity, the difference between the three groups was not
      statistically significant preoperatively (P > .10), but showed significant
      differences postoperatively (P < .007). The cohort's average preoperative
      corrected distance visual acuity was 0.01 +/- 0.04 logMAR (range: 0.0 to 0.18
      logMAR) and uncorrected distance visual acuity was 0.03 +/- 0.08 logMAR (range: 
      0.12 to 0.40 logMAR) 3 months postoperatively. CONCLUSIONS: SmartSurfACE
      maintained or slightly improved preoperative corneal asphericity for low to
      moderate myopic corrections (up to -6.00 D). This may provide advantages in the
      quality of vision and the onset of presbyopic symptoms after laser refractive
      surgery in myopic patients. [J Refract Surg. 2017;33(12):820-826.].

PMID- 29227511
TI  - Predictive Formula for Refraction of Autologous Lenticule Implantation for
      Hyperopia Correction.
AB  - PURPOSE: To create a formula to predict refractive correction of autologous
      lenticule implantation for correction of hyperopia (with myopia in one eye and
      hyperopia in the contralateral eye). METHODS: In this prospective study, 10
      consecutive patients (20 eyes) who had myopia in one eye and hyperopia in the
      contralateral eye were included. The preoperative spherical equivalent was -3.31
      +/- 1.73 diopters (D) for the myopic eyes and +4.46 +/- 1.97 D for the hyperopic
      eyes. For each patient, the myopic eye was treated with small incision lenticule
      extraction and the lenticule was subsequently implanted into the contralateral
      hyperopic eye. The average length of follow-up was 17 months. RESULTS: All of the
      operations were successful without complications. At the last visit, the efficacy
      index (postoperative uncorrected distance visual acuity/preoperative corrected
      distance visual acuity [CDVA]) of the hyperopic eyes was 0.94 +/- 0.35 and the
      safety index (postoperative CDVA/preoperative CDVA) was 1.36 +/- 0.38. No eyes
      lost any lines of visual acuity. Six of 10 (60%) of the implanted eyes were
      within +/-1.00 D of the intended refractive target. A predictive formula was
      derived: Lenticule implantation achieved correction (D) (LAC) = 1.224 Lenticule
      refractive power (D) (LRP) - 0.063 (R2 =0.92, P < .001). On corneal topography,
      there was a significant increase in the corneal anterior surface keratometry
      value postoperatively, whereas the posterior surface keratometry value remained
      stable (P > .05). CONCLUSIONS: Autologous lenticule implantation could provide a
      reliable method of correcting hyperopia. The refractive correction formula may
      require further verification and adjustment. [J Refract Surg. 2017;33(12):827
      833.].

PMID- 29227512
TI  - Efficacy and Safety Comparison Between Suberoylanilide Hydroxamic Acid and
      Mitomycin C in Reducing the Risk of Corneal Haze After PRK Treatment In Vivo.
AB  - PURPOSE: This study compared the efficacy and safety of suberoylanilide
      hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of
      corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo.
      METHODS: Corneal haze in rabbits was produced with -9.00 diopter PRK. A single
      application of SAHA (25 MUM) or MMC (0.02%) was applied topically immediately
      after PRK. Effects of the two drugs were analyzed by slit-lamp microscope,
      specular microscope, TUNEL assay, and immunofluorescence. RESULTS: Single topical
      adjunct use of SAHA (25 MUM) or MMC (0.02%) after PRK attenuated more than 95%
      corneal haze and myofibroblast formation (P < .001). SAHA did not reduce
      keratocyte density, cause keratocyte apoptosis, or increase immune cell
      infiltration compared to MMC (P < .01 or .001). Furthermore, SAHA dosing did not
      compromise corneal endothelial phenotype, density, or function in rabbit eyes,
      whereas MMC application did (P < .01 or .001). CONCLUSIONS: SAHA and MMC
      significantly decreased corneal haze after PRK in rabbits in vivo. SAHA exhibited
      significantly reduced short- and long-term damage to the corneal endothelium
      compared to MMC in rabbits. SAHA is an effective and potentially safer
      alternative to MMC for the prevention of corneal haze after PRK. Clinical trials
      are warranted. [J Refract Surg. 2017;33(12):834-839.].

PMID- 29227513
TI  - In Vivo Early Corneal Biomechanical Changes After Corneal Cross-linking in
      Patients With Progressive Keratoconus.
AB  - PURPOSE: To report early corneal biomechanical changes after corneal cross
      linking (CXL) in patients with keratoconus. METHODS: Thirty-four eyes of 34
      patients undergoing CXL for progressive keratoconus were included in this
      prospective clinical study. Dynamic corneal response (DCR) parameters obtained
      with the Corvis ST (OCULUS Optikgerate GmbH; Wetzlar, Germany) were assessed at
      baseline (day of CXL) and after 1 month of follow-up; conversely, corneal
      tomography with the Pentacam (OCULUS Optikgerate GmbH) was assessed at baseline
      and at 1, 3, and 6 months after CXL. RESULTS: At the last follow-up visit (123.7
      +/- 69.6 days), all morphological parameters including steepest point (Kmax) and
      thinnest corneal thickness (ThCT) indicated stabilization of keratoconus (P >
      .05). Comparative analyses showed a rise of corneal stiffness demonstrated by a
      significant increase of Stiffness Parameter A1 (SP-A1) and Highest Concavity (SP
      HC) and a significant decrease of Inverse Concave Radius (1/R) and Deformation
      Amplitude Ratio (DA Ratio) (P < .05). There was a significant correlation between
      the preoperative keratoconus characteristics (Kmax, Belin/Ambrosio final D value
      [BAD-D], and ThCT) and the DCR parameters (P < .05). Kmax and BAD-D showed a
      significant positive correlation with DA Ratio, Deflection Amplitude (DefA), and
      1/R and a significant negative correlation with SPA1 and SP-HC. ThCT showed a
      significant positive correlation with SP-A1 and SP-HC and a significant negative
      correlation with DA Ratio, DefA, and 1/R. CONCLUSIONS: This study suggests that
      the new DCR parameters of the Corvis ST are able to detect early changes in
      biomechanics following CXL and those that are measurable before corneal shape
      modifications take place. Based on these results, the authors suggest the use of
      these metrics to assess the early efficacy of cross-linking. [J Refract Surg.
      2017;33(12):840-846.].

PMID- 29227514
TI  - Management and Outcomes of Retained Lenticules and Lenticule Fragments Removal
      After Failed Primary SMILE: A Case Series.
AB  - PURPOSE: To describe the management of and report the outcomes following the
      removal of retained lenticules or lenticule fragments after a complicated small
      incision lenticule extraction (SMILE). METHODS: Three patients were referred for
      consultation due to intraoperative complications during SMILE. In case 1, the
      lenticule was torn during extraction and a central fragment was retained in the
      pocket. In case 2, the inferior part of the lenticule remained attached at the
      anterior plane and its detached, superior part was dislocated and folded at the
      inferior part of the pocket. In case 3, the lenticule was completely attached at
      the anterior plane. All cases underwent secondary surgery. The lenticule fragment
      was detached using the dissector's body and tip and was extracted using the
      advanced lenticule forceps. The retained lenticules were extracted after
      dissection of tissue bridges at the anterior plane and periphery. RESULTS:
      Postoperatively, all eyes showed improvement of visual acuity and topographic
      regularization of the anterior corneal curvature. Complete removal of lenticule
      remnants was accomplished in cases 1 and 2. In case 3, the photodisruption during
      primary SMILE was incomplete at a peripheral area next to the incision. A small
      peripheral fragment, corresponding to the described peripheral area, remained
      attached after the lenticule removal and was left in situ but did not have any
      impact on visual acuity and quality. CONCLUSIONS: Retained lenticules or
      lenticule fragments may induce irregular astigmatism and loss of visual acuity.
      Prompt removal restores visual acuity and induces the desired effect of the
      primary SMILE procedure. [J Refract Surg. 2017;33(12):848-853.].

PMID- 29227515
TI  - A Novel Corneal Remodeling Technique for the Management of Keratoconus.
AB  - PURPOSE: To describe a novel technique to reshape the ectatic cornea by means of
      crescent keratectomy performed with an excimer laser using a mask. METHODS: A
      crescent-shaped perforation at the base of the mask allowed the laser ablation to
      be directed only to the intended region, shielding the remaining cornea. This
      technique was performed in 3 eyes of 3 patients with keratoconus grade 2 to 3.
      Arcs of 180 degrees  and 360 degrees  had been performed depending on the
      severity of the keratoconus. The edges of the crescent were closed by 10-0 nylon
      interrupted sutures. RESULTS: At 1 year postoperatively, all cases showed
      improvement in visual acuity, keratometry, and corneal topography. The treatment
      also reduced optical aberrations and shortened the anterior chamber depth.
      CONCLUSIONS: Although the preliminary results are promising, there is a need to
      standardize a nomogram of this technique for treating keratoconus. [J Refract
      Surg. 2017;33(12):854-856.].

PMID- 29227516
TI  - Pediatric Ingestions and "Choosing Wisely".

PMID- 29227517
TI  - Intimate Partner Violence and Pediatric Practice.
AB  - Millions of parents, most of them mothers, are abused by an intimate partner each
      year in the United States. Intimate partner violence is all too common in homes
      with children; it's estimated that 15 million children are exposed each year. The
      short- and long-term impacts to child health and well-being are profound.
      Pediatric clinical practice represents an underutilized venue for assessment and
      intervention in the abuse of parents. This article summarizes the basic elements
      of an approach in practice. [Pediatr Ann. 2017;46(12):e438-e440.].

PMID- 29227518
TI  - Pediatric Ingestions.

PMID- 29227519
TI  - Pediatric Poisoning by Ingestion: Developmental Overview and Synopsis of National
      Trends.
AB  - The American Association of Poison Control Centers' National Poison Data
      Surveillance System provides real-time toxico-surveillance and epidemiologic
      trends, and pediatric ingestions comprise most of those reports. The sequences in
      social and physical developmental milestones from young childhood to adolescence
      reveal the vulnerability of these age groups to a wide variety of potential
      poisonous ingestions. Most pediatric ingestions are exploratory. Some common
      agents associated with pediatric fatalities include disc batteries, laundry
      detergent "pods," opioid analgesics, acetaminophen, benzodiazepines, and
      amphetamines. The pediatric provider can be a valuable resource at all points
      throughout a child's life, offering anticipatory guidance to caregivers targeting
      developmental changes associated with poisonous ingestions. [Pediatr Ann.
      2017;46(12):e443-e448.].

PMID- 29227520
TI  - Pediatric Toxicology: Household Product Ingestions.
AB  - Nonpharmaceutical household products are the most common substances involved in
      exploratory ingestions in young children. Fortunately, most of these products are
      not toxic if ingested in small volumes. However, there are several household
      products that have the potential to cause significant toxicity and, rarely,
      fatalities in young children. Key products reviewed in this article include
      alcohols, button batteries, corrosive cleaning products, laundry detergent pods,
      hydrocarbons, and magnets. [Pediatr Ann. 2017;46(12):e449-e453.].

PMID- 29227521
TI  - Pediatric Poisonings: The Risk of Over-the-Counter Pharmaceuticals.
AB  - Every week in the United States, 56% of children younger than age 18 years and
      82% of adults take at least one medication. Nonprescription medications,
      including acetaminophen and ibuprofen, are among the most commonly used
      pharmaceuticals across all age groups. Use of nonprescription medications,
      traditionally available over-the-counter, has become ubiquitous. Unfortunately,
      with such abundant use there is an associated risk for therapeutic misuse,
      intentional misuse, and even abuse. [Pediatr Ann. 2017;46(12):e454-e458.].

PMID- 29227522
TI  - Pediatric Pharmaceutical Ingestions.
AB  - Pharmaceutical ingestions comprise an important part of pediatric toxicology.
      Based on the 2015 Annual Report of the American Association of Poison Control
      Centers' National Poison Data System, coupled with recent epidemiology articles
      on the topic of pediatric toxicology, it is apparent that poison prevention
      education has not been completely successful in decreasing exposures to toxic
      drugs. From the unintentional ingestion in a toddler due to unsafe storage to the
      intentional adolescent ingestion for misuse and abuse, pharmaceutical medications
      continue to cause harm. Access to adult prescription drugs in the home accounted
      for most of the exposures in children age <=5 years as well as adolescents age 13
      to 19 years. Ingestions resulting from more common pharmaceutical exposures are
      discussed with the hope of increasing awareness about the need for added
      vigilance. [Pediatr Ann. 2017;46(12):e459-e465.].

PMID- 29227523
TI  - Childhood Ingestions of Environmental Toxins: What Are the Risks?
AB  - Infants and children are at higher risk than adolescents and adults for exposure
      to environmental toxins via ingestion for a number of reasons: their smaller size
      (and proportionately larger dose of ingested toxins), their closer proximity to
      the ground, dirt, and indoor dust, their boundless curiosity and oral exploratory
      behaviors, pica habits that may persist into school-age for children with autism
      or other developmental delays, their proportionately larger daily water and milk
      intake, and food preferences that differ markedly from adolescents and adults.
      Children depend on adults to protect them and keep their home environment safe.
      Pediatric care providers can integrate environmental health topics into their
      well-child care practices, offering guidance and resources to parents concerned
      with reducing the risks to their children posed by hazards in their homes,
      daycare centers, preschools, schools, and the other environments in which they
      spend time. [Pediatr Ann. 2017;46(12):e466-e471.].

PMID- 29227524
TI  - Pediatric Scoliosis and Kyphosis: An Overview of Diagnosis, Management, and
      Surgical Treatment.
AB  - Evaluation of pediatric spinal deformity requires knowledge of special
      orthopaedic testing and radiographic interpretation. The determination of
      recommendations for treatment of spinal abnormalities in children can be
      challenging and at times complex, as treatment options are dependent upon a
      variety of factors. The etiology of scoliosis or kyphosis, presence or absence of
      vertebral anomalies, symptoms, magnitude of the curve, physiologic/skeletal age,
      and evidence of and risk of progression all require consideration and play a role
      in the shared decision-making process. This article provides an overview of
      relevant information and includes research outcomes to support the care of
      pediatric patients with spinal deformities. [Pediatr Ann. 2017;46(12):e472
      e480.].

PMID- 29227525
TI  - Functional electrical stimulation and ankle foot orthoses provide equivalent
      therapeutic effects on foot drop: A meta-analysis providing direction for future
      research.
AB  - OBJECTIVE: To compare the randomized controlled trial evidence for therapeutic
      effects on walking of functional electrical stimulation and ankle foot orthoses
      for foot drop caused by central nervous system conditions. DATA SOURCES: MEDLINE,
      CINAHL, Cochrane Central Register of Controlled Trials, REHABDATA, PEDro, NIHR
      Centre for Reviews and Dissemination, Scopus and clinicaltrials.gov. STUDY
      SELECTION: One reviewer screened titles/abstracts. Two independent reviewers then
      screened the full articles. DATA EXTRACTION: One reviewer extracted data, another
      screened for accuracy. Risk of bias was assessed by 2 independent reviewers using
      the Cochrane Risk of Bias Tool. DATA SYNTHESIS: Eight papers were eligible; 7
      involving participants with stroke and 1 involving participants with cerebral
      palsy. Two papes reporting different measures from the same trial were grouped,
      resulting in 7 synthesized randomized controlled trials (n= 464). Meta-analysis
      of walking speed at final assessment (p = 0.46), for stroke participants (p =
      0.54) and after 4-6 weeks' use (p = 0.49) showed equal improvement for both
      devices. CONCLUSION: Functional electrical stimulation and ankle foot orthoses
      have an equally positive therapeutic effect on walking speed in non-progressive
      central nervous system diagnoses. The current randomized controlled trial
      evidence base does not show whether this improvement translates into the user's
      own environment or reveal the mechanisms that achieve that change. Future studies
      should focus on measuring activity, muscle activity and gait kinematics. They
      should also report specific device details, capture sustained therapeutic effects
      and involve a variety of central nervous system diagnoses.

PMID- 29227526
TI  - Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits:
      Antihypertensive, Antioxidant, and Antidiabetic Properties.
AB  - Cardiovascular diseases and diabetes are the biggest causes of death globally.
      Therefore, prevention of these diseases is a focus of pharmaceuticals and
      functional food manufacturers. This review summarizes recent research trends and
      scientific knowledge in seaweed protein-derived peptides with particular emphasis
      on production, isolation and potential health impacts in prevention of
      hypertension, diabetes and oxidative stress. The current status and future
      prospects of bioactive peptides are also discussed. Bioactive peptides have
      strong potential for use in therapeutic drug and functional food formulation in
      health management strategy, especially cardiovascular disease and diabetes.
      Seaweeds can be used as sustainable protein sources in the production of these
      peptide-based drugs and functional foods for preventing such diseases. Many
      studies have reported that peptides showing angiotensin converting enzyme
      inhibition, antihypertensive, antioxidative and antidiabetics activities, have
      been successfully isolated from seaweed. However, further research is needed in
      large-scale production of these peptides, efficient isolation methods,
      interactions with functional foods and other pharmaceuticals, and their ease to
      digestion in in vivo studies and safety to validate the health benefits of these
      peptides.

PMID- 29227527
TI  - M2 muscarinic receptor activation inhibits cell proliferation and migration of
      rat adipose-mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs), also known as stromal mesenchymal stem cells, are
      multipotent cells, which can be found in many tissues and organs as bone marrow,
      adipose tissue and other tissues. In particular MSCs derived from Adipose tissue
      (ADSCs) are the most frequently used in regenerative medicine because they are
      easy to source, rapidly expandable in culture and excellent differentiation
      potential into adipocytes, chondrocytes, and other cell types. Acetylcholine
      (ACh), the most important neurotransmitter in Central nervous system (CNS) and
      peripheral nervous system (PNS), plays important roles also in non-neural tissue,
      but its functions in MSCs are still not investigated. Although MSCs express
      muscarinic receptor subtypes, their role is completely unknown. In the present
      work muscarinic cholinergic effects were characterized in rat ADSCs. Analysis by
      RT-PCR demonstrates that ADSCs express M1-M4 muscarinic receptor subtypes,
      whereas M2 is one of the most expressed subtype. For this reason, our attention
      was focused on M2 subtype. By using the selective M2 against Arecaidine Propargyl
      Ester (APE) we performed cell proliferation and migration assays demonstrating
      that APE causes cell growth and migration inhibition without affecting cell
      survival. Our results indicate that ACh via M2 receptors, may contribute to the
      maintaining of the ADSCs quiescent status. These data are the first evidence that
      ACh, via muscarinic receptors, might contribute to control ADSCs physiology.

PMID- 29227528
TI  - The Impact of Long-Term Intake of Phenolic Compounds-Rich Grape Pomace on Rat Gut
      Microbiota.
AB  - : The aim of this work is to evaluate the impact on the rat microbiota of long
      term feeding with phenolic compounds (PC) rich grape pomace extracts. Thirty, 2
      mo-old rats, were divided into 5 groups. Four groups were treated with different
      concentrations of PC (2.5, 5, 10, and 20 mg/kg/d diluted in 0.1% DMSO), and 1
      group received 0.1% Dimethyl Sulfoxide (DMSO) alone (control group). The daily
      treatment lasted 14 mo. Major phenolic compounds constituents were characterized
      by the high-performance liquid chromatography and free radical scavenging
      capacity was measured by means of the DPPH assay. Fecal samples from young rats
      (2-mo old), and rats daily fed with PC or DMSO were collected at 6 and 14 mo
      posttreatment. The gut microbiota composition was analyzed by quantitative
      polymerase chain reaction. Bifidobacterium was significantly higher in the groups
      PC 2.5 and PC 5 than in control and young rats. Lactobacillus decreased with time
      in all treated and untreated groups. Bacteroides, Clostridium leptum subgroup
      (Clostridium cluster IV), and Enterococcus were not significantly changed by PC
      at any concentration when compared to control; nevertheless, after 14 mo of
      treatment all concentrations of PC abolished the increase of Clostridium sensu
      stricto (cluster I) (Clostridium Cluster I) observed in the control group when
      compared to young rats. PC do modulate selectively rat gut microbiome to a
      healthier phenotype in long-term feeding rats, and could counteract the adverse
      outcomes of aging on gut bacterial population. PRACTICAL APPLICATION: This
      research shows that phenolic-rich grape pomace extracts exhibiting a high
      antioxidant activity, selectively modulate rat gut microbiota to a healthier
      phenotype within age in a long-term feeding rats.

PMID- 29227529
TI  - Role of IL-6-mediated expression of NS5ATP9 in autophagy of liver cancer cells.
AB  - This study aimed to investigate the relationship between interleukin-6 (IL-6) and
      NS5ATP9 in autophagy of liver cancer cells. Autophagy is one of the important
      regulators of the replication of hepatitis C virus and the survival of tumors. IL
      6 is a multifunctional cytokine that plays an important role in autophagy and
      development of many kinds of tumors. However, the role of IL-6 in autophagy has
      not been fully explored. A previous study had shown that a novel gene, NS5ATP9,
      could modulate autophagy. The present study demonstrated that human IL-6
      recombinant protein induced autophagy of HepG2 cells. Conversely, autophagy
      decreased after IL-6 was silenced or neutralized with monoclonal antibody against
      human IL-6. In addition, NS5ATP9 was upregulated by IL-6 via nuclear factor
      kappaB activation, as detected by Western blot. Further studies indicated that
      the induction of autophagy by IL-6 could be attenuated by silencing NS5ATP9.
      Interestingly, the expression of NS5ATP9, in turn, resulted in the upregulation
      of IL-6. In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while
      NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy.

PMID- 29227530
TI  - Systematic review and network meta-analysis of methods of mesh fixation during
      laparoscopic ventral hernia repair.
AB  - BACKGROUND: Ventral hernia repairs are common and have high recurrence rates.
      They are usually repaired laparoscopically with an intraperitoneal mesh, which
      can be fixed in various ways. The aim was to evaluate the recurrence rates for
      the different fixation techniques. METHODS: This systematic review included
      studies with human adults with a ventral hernia repaired with an intraperitoneal
      onlay mesh. The outcome was recurrence at least 6 months after operation. Cohort
      studies with 50 or more participants and all RCTs were included. PubMed, Embase
      and the Cochrane Library were searched on 22 September 2016. RCTs were assessed
      with the Cochrane risk-of-bias assessment tool and cohort studies with the
      Newcastle-Ottawa scale. Studies comparing fixation techniques were included in a
      network meta-analysis, which allowed comparison of more than two fixation
      techniques. RESULTS: Fifty-one studies with a total of 6553 participants were
      included. The overall crude recurrence rates with the various fixation techniques
      were: absorbable tacks, 17.5 per cent (2 treatment groups); absorbable tacks with
      sutures, 0.7 per cent (3); permanent tacks, 7.7 per cent (20); permanent tacks
      with sutures, 6.0 per cent (25); and sutures, 1.5 per cent (6). Six studies were
      included in a network meta-analysis, which favoured fixation with sutures.
      Although statistical significance was not achieved, there was a 93 per cent
      chance of sutures being better than one of the other methods. CONCLUSION: Both
      crude recurrence rates and the network meta-analysis favoured fixation with
      sutures during laparoscopic ventral hernia repair.

PMID- 29227531
TI  - Discovery of a novel six-long non-coding RNA signature predicting survival of
      colorectal cancer patients.
AB  - Colorectal cancer (CRC) is one of the most leading causes of cancer deaths
      worldwide. In the study, we aimed to identify key long non-coding RNAs (lncRNAs)
      significantly associated with prognosis of CRC and develop an expression-based
      lncRNA signature to provide survival risk prediction for CRC patients. LncRNA
      expression profiles and clinical information of CRC patients were collected from
      The Cancer Genome Atlas (TCGA) database. Six hundred and eighteen differentially
      expressed lncRNAs were identified between CRC and normal tissues. After
      univariate and multivariate Cox regression analysis for these differentially
      expressed lncRNAs and overall survival of CRC patients, six predictive lncRNAs
      (RP1-170O19.17, RP11-785D18.3, RP11-798K3.2, XXbac-B476C20.9, RP11-481J13.1, and
      RP11-167H9.4) were finally screened out to construct a six-lncRNA signature,
      based on which patients in the training dataset were divided into the high-risk
      and low-risk group with significantly different overall survival. ROC curve
      analysis demonstrated competitive performance of the six-lncRNA signature. The
      prognostic power of the six-lncRNA signature was successfully validated in the
      testing and entire dataset. Multivariate Cox regression analysis and
      stratification analysis further suggested that the six-lncRNA signature was
      independent of other conventional clinical variables for survival prediction in
      CRC patients. Functional enrichment analysis revealed the possible roles of these
      predictive lncRNAs in some cancer-related biological processes and pathways. Our
      study demonstrated the promising potential of the novel six-lncRNA signature as
      an independent biomarker for survival prediction of CRC patients.

PMID- 29227532
TI  - LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1
      expression in hepatocellular carcinoma cell.
AB  - Increasing evidence highlights the important role of XIST, a long non-coding RNA
      (lncRNA), in the regulation of multiple cancers. However, the underlying
      mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be
      explored. Herein, intended to investigate the functional role of XIST in HCC
      initiation and progression. We first detected that XIST was significantly
      upregulated in HCC tissues and associated with tumor size and vascular invasion.
      Gain- and loss-of-function of XIST further presented that XIST promoted the
      progression of HCC cells, including proliferation, migration, and invasion.
      Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found
      that XIST could target miR-194-5p and thus decrease miR-194-5p expression.
      Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on
      the proliferation and invasion of HCC cells. We further elucidated such rescue
      role might through derepressing MAPK1 expression, the target of miR-194-5p. In
      brief, the above results elucidate the important role of XIST in HCC
      tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and
      a novel therapeutic target for treating HCC.

PMID- 29227533
TI  - Functional Magnetic Nanoparticles for Highly Efficient Cholesterol Removal.
AB  - In this study, magnetic nanoparticles functionalized with carboxylated beta
      cyclodextrin (CM-beta-CD; referred to Fe3 O4 @CM-beta-CD) were synthesized and
      used for the efficient removal of cholesterol from milk and egg yolk via host
      guest interactions. The results of Fourier-transform infrared, X-ray
      photoelectron spectroscopy, and thermogravimetric analysis indicated that the CM
      beta-CD was successfully conjugated to the surface of Fe3 O4 , and the amount of
      CM-beta-CD attached on Fe3 O4 @CM-beta-CD was determined to be 9.164%. The X-ray
      diffraction and transmission electron microscopy data revealed that the process
      of CM-beta-CD coating did not result in a phase change of the Fe3 O4 , and the
      Fe3 O4 @CM-beta-CD nanoparticles were determined to have an average size of about
      15 nm. The results of isotherm adsorption and kinetic properties indicated that
      CM-beta-CD functionalization increased the cholesterol removal efficiency, and
      the characteristics of cholesterol adsorption on Fe3 O4 @CM-beta-CD were fitted
      well with the Langmuir adsorption model and Lagergren pseudo-1st-order kinetic
      models. Furthermore, compared with the Fe3 O4 nanoparticles, the functionalized
      Fe3 O4 @CM-beta-CD nanoparticles exhibited greater cholesterol removal
      efficiency, and saponification of the milk and egg yolk was found to be
      beneficial for the cholesterol removal; using the Fe3 O4 @CM-beta-CD
      nanoparticles, 98.8% and 94.6% of the cholesterol was extracted in 1 h from
      saponified milk and egg yolk, respectively, and the Fe3 O4 @CM-beta-CD
      nanoparticles still displayed efficient cholesterol removal after 6 reuses.

PMID- 29227534
TI  - Family functioning evaluated by family members of older patients and nurses in
      emergency departments.
AB  - The functioning of families in emergency departments (EDs) encompasses the level
      at which the families of older patients perform as a whole during the ED stay.
      Currently, little is known about how the families of older patients function in
      EDs. In this study, family functioning included the subareas of family strengths,
      structural factors and relationships both inside and outside the family. The
      study aimed to describe family functioning in EDs as evaluated by both the family
      members (n = 111) of older patients and nurses (n = 93). The data were collected
      from four Estonian hospitals, and the scale used was the Family Functioning,
      Health and Social Support scale. The results showed that both the family members
      and nurses evaluated family functioning and all its subareas as being moderate.
      Family structural factors were found to be associated with the family members'
      social status. The scores in the subareas were higher when older patients had
      received help from family members before the ED visit. The family members and
      nurses differed significantly in the scores they gave for family functioning in
      general and for all the subareas. No association was found between family
      functioning as rated by nurses and the families' demographic characteristics.
      These results suggest that nurses should pay more attention to family functioning
      in general and to the structural factors within the family, including internal
      relationships, while older patients are in the ED. Comprehensive knowledge about
      how families function during an ED stay may help nurses to better meet the needs
      of older patients and their families and help them to prepare families to provide
      aftercare at home. Our findings support the idea that healthcare organisation and
      delivery should be more family centred.

PMID- 29227535
TI  - Antidiabetic and Lipid-Lowering Effects of the Polyphenol Extracts from the
      Leaves of Clausena lansium (Lour.) Skeels on Streptozotocin-Induced Type 2
      Diabetic Rats.
AB  - : Clausena lansium (Lour.) Skeels (Wampee) is widely grown in China and
      considered as a healthy fruit. Its leaves are also considered as traditional
      herbs. This study analyzed polyphenol compounds in polyphenol extracts of the
      leaves C. lansium (lour.) Skeels (PEL) and investigated the protective effect of
      PEL against hyperglycemia and hyperlipidemia in T2DM rats. The result showed that
      PEL is composed mainly of gallic acid, chlorogenic acid, coffee acid, ferulic
      acid, and rutin. PEL could obviously relieve some symptoms of T2DM rats,
      including emaciation, hyperhidrosis, polyphagia, diuresis, liver swelling,
      kidney, and pancreas hypertrophy, as well as reduce fasting blood glucose.
      Moreover, the supplementation of PEL significantly ameliorated lipids disorder
      and protected liver in T2DM rats, including fat accumulation, improvement of
      lipid distribution and hepatocyte protection. These results indicate that the
      Oral of PEL have potential effects of against hyperglycemia and hyperlipidemia in
      diabetic disorders. PRACTICAL APPLICATION: The leaves Clausena lansium (lour.)
      Skeels is rich in polyphenol and other ingredients. In this research, the
      preliminary study shows that PEL can reduce fasting blood glucose and improve
      lipids disorder in rats, which will bring to diabetic patients a way to improve
      the disease and enhance the quality of life. The PEL therefore can be used for
      the production of pharmaceutical raw materials and the design of novel functional
      foods by simple conversion.

PMID- 29227536
TI  - MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell
      proliferation, invasion, and inhibits apoptosis in gastric cancer.
AB  - Gastric cancer ranks as the second leading cause of malignancy-related death
      worldwide, and always diagnosed at advanced stage. MicroRNA-222-3p (miR-222-3p)
      is aberrantly upregulated in various malignant tumors including gastric cancer,
      but its role and underlying molecular mechanisms in gastric cancer remain largely
      unknown. Helicobacter pylori (H. pylori) infection acts as a trigger in the
      development of gastric cancer, and increasing evidence suggests that H. pylori
      affects microRNA expression. In this study, gastric cancer tissue samples were
      divided into H. pylori positive group (+) and negative group (-). QRT-PCR showed
      that miR-222-3p was significantly upregulated in H. pylori (+) group compared
      with H. pylori (-) group, and luciferase reporter assays identified homeodomain
      interacting protein kinase 2 (HIPK2) as a novel target of miR-222-3p in gastric
      cancer. Immunohistochemistry revealed that HIPK2 levels were decreased in H.
      pylori (+) group compared with H. pylori (-). After that, functional experiments
      indicated that miR-222-3p overexpression promoted the proliferation and invasion,
      while inhibiting apoptosis of SGC7901 gastric cancer cells, but miR-222-3p
      knockdown exhibited the opposite effects. Also, HIPK2 knockdown induced similar
      effects as miR-222-3p overexpression in SGC7901 cells. Nude mouse experiments
      further suggested that HIPK2 overexpression signally attenuated the enhancing
      effect of miR-222-3p overexpression on cell proliferation, indicating that the
      effect of miR-222-3p on gastric cancer progression depends on HIPK2, at least in
      part. Overall, our results demonstrated that miR-222-3p/HIPK2 signal pathway
      regulated gastric cancer cell proliferation, apoptosis, and invasion, provided a
      novel therapeutic target for the treatment of gastric cancer infected by H.
      pylori.

PMID- 29227537
TI  - Retraction: Han, M., Nie, J., Li, Y., Zhu, Y. and Wu, G. (2018), NGAL gene
      silencing inhibits proliferation and promotes apoptosis of human gastric cancer
      cells: an in vivo and in vitro study. J. Cell. Biochem. Accepted Author
      Manuscript. doi:10.1002/jcb.26549.
AB  - The above article, published online on 11 December 2017 in Wiley Online Library
      (wileyonlinelibrary.com), has been withdrawn by agreement between the authors,
      the journal Editor in Chief, Gary Stein and Wiley Periodicals, Inc. The
      withdrawal has been agreed due to determination by the authors that the data
      concerning the GC cell lines presented in this publication needs further study
      and analysis.

PMID- 29227538
TI  - Abberent expression of NOR1 protein in tumor associated macrophages contributes
      to the development of DEN-induced hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and
      the sixth most common lethal cancer worldwide. Recent evidences demonstrated that
      oxidored nitro domain containing protein 1 (NOR1), a putative tumor suppressor
      gene, is overexpressed in human HCC tissues. However, the role of NOR1 in HCC
      development remains unclear. Here, we described that NOR1 protein level is
      elevated in HCC and is associated with poorer clinical outcome. However, ecotopic
      overexpression of NOR1 protein in human HCC cell line HepG2 cells had no effect
      on cells proliferation, migration, and clonality. Immunofluoresence assay
      indicates NOR1 protein is mainly expressed at CD163 positive M2 tumor associated
      macrophages (TAMs). To explore the role of NOR1 in the development of HCC, we
      interrogated the susceptibility of mice lacking the NOR1 gene to DEN-induced
      hepatocarcinogenesis. NOR1 deficient mice displayed resistance to DEN-induced
      HCC. We also demonstrate that mNOR1 protein is enriched in F4/80 positive Kupffer
      cells (KCs) infiltrated in DEN induced murine HCC tissues. Loss of NOR1 led to
      increase of iNOS whereas decrease of Arg1, Ym1 expression in KCs. Overexpression
      of NOR1 in THP-1 macrophages led to decrease of iNOS but increase of Arg1.
      Mechanistic investigations showed that inflammatory cytokines IL-6, TNF-alpha
      production, and NF-kappaB activation were also decreased in NOR1 knockout mice
      exposed to DEN treatment. Our data suggested that NOR1 is overexpressed in HCC
      associated TAMs and promotes M2 alternative polarization. Genetic deletion of
      NOR1 in mice leads to impairment of IL-6 production and NF-kappaB activation,
      which in turn attenuates DEN-induced HCC development.

PMID- 29227539
TI  - Mir-29b promotes human aortic valve interstitial cell calcification via
      inhibiting TGF-beta3 through activation of wnt3/beta-catenin/Smad3 signaling.
AB  - Herein, we hypothesized that pro-osteogenic MicroRNAs (miRs) could play
      functional roles in the calcification of the aortic valve and aimed to explore
      the functional role of miR-29b in the osteoblastic differentiation of human
      aortic valve interstitial cells (hAVICs) and the underlying molecular mechanism.
      Osteoblastic differentiation of hAVICs isolated from human calcific aortic valve
      leaflets obtained intraoperatively was induced with an osteogenic medium.
      Alizarin red S staining was used to evaluate calcium deposition. The protein
      levels of osteogenic markers and other proteins were evaluated using western
      blotting and/or immunofluorescence while qRT-PCR was applied for miR and mRNA
      determination. Bioinformatics and luciferase reporter assay were used to identify
      the possible interaction between miR-29b and TGF-beta3. Calcium deposition and
      the number of calcification nodules were pointedly and progressively increased in
      hAVICs during osteogenic differentiation. The levels of osteogenic and
      calcification markers were equally increased, thus confirming the mineralization
      of hAVICs. The expression of miR-29b was significantly increased during
      osteoblastic differentiation. Furthermore, the osteoblastic differentiation of
      hAVICs was significantly inhibited by the miR-29b inhibition. TGF-beta3 was
      markedly downregulated while Smad3, Runx2, wnt3, and beta-catenin were
      significantly upregulated during osteogenic induction at both the mRNA and
      protein levels. These effects were systematically induced by miR-29b
      overexpression while the inhibition of miR-29b showed the inverse trends.
      Moreover, TGF-beta3 was a direct target of miR-29b. Inhibition of miR-29b hinders
      valvular calcification through the upregulation of the TGF-beta3 via inhibition
      of wnt/beta-catenin and RUNX2/Smad3 signaling pathways.

PMID- 29227540
TI  - Human T-lymphotropic virus 1 (HTLV-1) pathogenesis: A systems virology study.
AB  - The main mechanisms of interaction between Human T-lymphotropic virus type 1
      (HTLV-1) and its hosts in the manifestation of the related disease including HTLV
      1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell
      leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the
      changes in the genes expression toward an asymptomatic or symptomatic states. To
      this end, the systems virology analysis was performed. Firstly, the
      differentially expressed genes (DEGs) were taken pairwise among the four sample
      sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the
      protein-protein interaction networks were reconstructed utilizing the hub genes.
      In conclusion, the pathways of cells proliferation and transformation were
      identified in the ACs state. In addition to immune pathways in ATLL, the
      inflammation and cancer pathways were discened in both diseases of ATLL and
      HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help
      to design the drugs in the future.

PMID- 29227541
TI  - Protective effects of microRNA-431 against cerebral ischemia-reperfusion injury
      in rats by targeting the Rho/Rho-kinase signaling pathway.
AB  - This study investigates the protective effects of miR-431 against cerebral
      ischemia-reperfusion injury through the Rho/Rho-kinase signaling pathway. SD rats
      were randomly classified into normal, sham, and model (middle cerebral artery
      occluded) groups. Rho expression and cerebral infarction were visualized by
      immunohischemistry and TTC staining, respectively. qRT-PCR and western blotting
      were used to measure mRNA and protein expression of miR-431 and Rho/Rho-kinase
      signaling pathway-related genes. Hippocampal neurons were extracted and assigned
      into normal, blank, negative control (NC), miR-431 mimics, miR-431 inhibitors,
      siRNA-Rho, and miR-431 inhibitors + siRNA-Rho groups. Proliferation and apoptosis
      were detected by MTT and flow cytometry, respectively. Compared with the normal
      group, the model group showed elevated Rho expression, area of cerebral
      infarction, and expressions of Rho/Rho-kinase related genes but reduced miR-431
      expression. Compared with the blank group, expression of Rho, Rho-kinase alpha,
      and Rho-kinase beta decreased and miR-431 expression increased in the miR-431
      mimics and siRNA-Rho groups, and the tendency reversed in the miR-431 inhibitors
      group. Enhanced proliferation and inhibited apoptosis were exhibited in the miR
      431 mimics and siRNA-Rho groups while results in the miR-431 inhibitors group
      reversed. Findings obtained from this study indicated that miR-431 confers
      protection against cerebral ischemia-reperfusion injury through negatively
      regulating the Rho/Rho-kinase signaling pathway.

PMID- 29227542
TI  - Characterization of Peanut Oil Bodies Integral Proteins, Lipids, and Their
      Associated Phytochemicals.
AB  - : A microscopic image of a section of a peanut seed shows that oil bodies (OBs)
      are a small droplet of oil that is dispersed throughout the whole seed. The
      protein profile of peanut's OBs recovered using the aqueous extraction method at
      different pH was found to have 2 oleosin isoforms of 14 and 16 kDa. Moreover, OBs
      essential amino acids are 1.52 higher than those in the PPI. Oleic acid and
      linoleic acid are the major fatty acids in both cold press peanut oil and OBs
      regardless of pH. Tocopherol content went from 270.76 to 278.2 mg/g when pH got
      increased. delta-Tocopherols are slightly associated with peanut OBs, as it was
      resistant to the alkaline washing; however, alpha-tocopherols were discovered to
      be weakly associable. On the contrary, phytosterols content decreased when pH got
      increased, with 631.49 MUg/g for pH 6.8 and 614.96 MUg/g for pH 11.0. PRACTICAL
      APPLICATION: Peanut oil is widely used in food industries in the form of
      emulsified oil. OBs can be presented as a better alternative solution, which is
      stable emulsified oil, with high content of antioxidant and phytosterols. Our
      results showed that peanut OBs are rich in nutritional components such as
      essential amino acids, unsaturated fatty acids, vitamin E, and phytosterols.
      Moreover, peanut OBs are surrounded with 2 oleosin isoforms and caleosin, which
      offer more stability to the emulsion system. Thus, peanut OBs can be perfect for
      food like mayonnaise and vinaigrettes products in the form of encapsulated oil
      with high content of vitamin E.

PMID- 29227543
TI  - Edible Coating Using a Chitosan-Based Colloid Incorporating Grapefruit Seed
      Extract for Cherry Tomato Safety and Preservation.
AB  - : Grapefruit seed extract (GSE)-containing chitosan-based coating was developed
      and applied to cherry tomatoes to protect them from Salmonella invasion and
      improve their storability. The coating colloids were produced by mixing a
      chitosan colloid (1% [w/w] chitosan) with GSE at various concentrations (0.5%,
      0.7%, 1.0%, and 1.2% [w/w]) using high-shear mixing (10000 rpm, 2 min). Coatings
      with chitosan colloids containing GSE at 0.0%, 0.5%, 0.7%, and 1.0% (w/w)
      inactivated Salmonella on cherry tomatoes by 1.0 +/- 0.3, 1.2 +/- 0.3, 1.6 +/-
      0.1, and 2.0 +/- 0.3 log CFU/cherry tomato, respectively. Coatings both with and
      without GSE (1.0%) effectively inhibited the growth of Salmonella and total
      mesophilic aerobes, reduced CO2 generation, and retarded titratable acidity
      decrease during storage at 10 and 25  degrees C. The advantage of incorporating
      GSE in the formulation was demonstrated by delayed microorganism growth and
      reduced weight loss at 25  degrees C. The chitosan-GSE coating did not affect
      lycopene concentration, color, and sensory properties (P > 0.05). Chitosan-GSE
      coating shows potential for improving the microbiological safety and storability
      of cherry tomatoes, with stronger efficacy at 25  degrees C than that of chitosan
      coating without GSE. PRACTICAL APPLICATION: A novel chitosan coating containing
      grape fruit seed extract (GSE) improved the microbiological safety against
      Salmonella and storability of cherry tomatoes without altering their flavor,
      demonstrating its strong potential as an effective postharvest technology.
      Chitosan coating containing GSE might be preferable over chitosan coating without
      GSE for application to tomatoes that are stored at room temperature in that it
      more effectively inhibits microbial growth and weight loss than the coating
      without GSE at 25  degrees C.

PMID- 29227544
TI  - A fast and accurate isotope dilution GC-IT-MS/MS method for determination of
      eugenol in different tissues of fish: Application to a depletion study in
      mandarin fish.
AB  - An accurate, rapid and effective method was established for determination of
      eugenol in plasma, muscle, skin, liver, kidney and gill of fish using gas
      chromatography-ion trap tandem mass spectrometry. Samples of muscle, skin, liver,
      kidney and gill were prepared using the modified QuEChERS (quick, easy, cheap,
      effective, rugged and safe) procedure, and a plasma sample was prepared by a
      liquid-liquid extraction procedure. Eugenol was monitored in <7 min using an
      electron-ionization source in MS/MS mode and quantified by an internal standard
      of eugenol-d3 . The limit of detection was 5.0 MUg/kg, and the limit of
      quantification was 10.0 MUg/kg. The calibration curve was linear in the range of
      5-1000 MUg/L (R2 = 0.9996). Intra- and inter-day precisions of eugenol expressed
      as relative standard deviation were within 9.74%, and the accuracy exhibited a
      relative error ranging from -2.20 to 8.89%. The developed method was successfully
      used to study the elimination regularity of eugenol in mandarin fish.

PMID- 29227545
TI  - Overexpression of Sirt6 is a novel biomarker of malignant human colon carcinoma.
AB  - Sirt family has been reported playing a significant role in the cancer
      development, especial its deacetylase activity plays a key function, but whether
      SIRT6 plays a role in mediating tumor epithelial-mesenchymal transition (EMT) and
      metastasis in colon cancer has not been explored. Here, the mass spectrometry and
      co-immunoprecipitation assays were utilized to detect that SIRT6 was physically
      associated with transcription factor snail. Most important, HCT116 cells
      transfected with SIRT6 shRNA reversed EMT, while increased the expression of
      TET1, and the HCT116 cells transfected with SIRT6 displayed the contrary
      tendency. Transwell invasion assay, soft agar assay, as well as colony formation
      together showed that SIRT6 promoted cell EMT and tumorigenesis in vitro. We also
      found SIRT6 is a reader of snail. ChIP as well as qChIP suggested H3K9 binding on
      the promoter of TET1 dependent on SIRT6. SIRT6 promoted EMT process through two
      different ways, one is as a reader of snail, and other way was the suppression of
      TET1 transcription. These two ways are all dependent on its H3K9 deacetylase
      activity. Further, patient samples collected showed that SIRT6 was significantly
      increased in colon cancer samples, and its higher expression was correlated with
      poor prognosis, worse overall survivals. Together, our experiments revealed the
      mechanism for SIRT6 in facilitating tumorigenesis and metastasis of colon cancer
      cells, suggesting that SIRT6 might be a potential therapeutic target for treating
      colon cancer.

PMID- 29227546
TI  - High levels of extracellular ATP lead to chronic inflammatory response in
      melanoma patients.
AB  - Skin cancer represents a serious public health problem and melanoma is considered
      the most significant due to its high metastasis capacity. Evasion mechanisms are
      the main characteristic of these tumor cells to escape of immune response.
      Extracellular nucleotides and nucleosides play an important role in inflammatory
      and immune responses. In this study, we analyzed the expression and activity of
      purinergic system enzymes in platelets and lymphocytes, ATP levels
      quantification, as well the level of pro and anti-inflammatory interleukins in
      the serum of 23 patients with surgical melanoma removal (CM group) and 23 control
      subjects (CT group). Results showed a decrease in ATP, ADP, and AMP hydrolysis
      and an increase in ATP levels quantification in CM group. The pro-inflammatory
      cytokines were elevated in CM group when compared to CT group. These results
      suggest an inflammatory process, even after surgical removal, due to elevated
      extracellular ATP levels. Besides, CM group displayed an increase in IL-10 levels
      and an increased in ADA activity in platelets and lymphocytes. Once adenosine and
      IL-10 are anti-inflammatory molecules, these results indicate a down-regulation
      of immune system front to malignant process. The alteration in nucleotide and
      nucleoside hydrolysis reinforces the purinergic systems role in this cancer.
      Therefore, even after surgical removal, the purinergic system can develop a
      chronic inflammatory micro-environment that can influence directly on relapse or
      metastasis.

PMID- 29227547
TI  - A network meta-analysis on the short-term efficacy and adverse events of
      different anti-osteoporosis drugs for the treatment of postmenopausal
      osteoporosis.
AB  - A network meta-analysis was conducted to compare the short-term efficacy and
      adverse events of different drugs for the treatment of postmenopausal
      osteoporosis (PMO), providing a more effective treatment for PMO. We initially
      searched through various databases like PubMed, Cochrane Library, and EMBASE from
      inception till October 2016. All randomized controlled trials (RCTs) of drugs for
      the treatment of PMO were included for direct and indirect comparison. A
      combination of direct and indirect evidence of different inhibitors of anti
      diabetic drugs for treatment of PMO were considered for calculating the weighted
      mean difference (WMD) value or odd ratio (OR) value and to draw surface under the
      cumulative ranking (SUCRA) curves. Twenty-seven RCTs were ultimately incorporated
      into this network meta-analysis comprising of 48 200 patients suffering from PMO.
      The network meta-analysis revealed that compared with placebo, alendronate had
      better efficacy on improving bone mineral density (BMD) at lumbar spine, femoral
      neck, and total hip. Risedronate and raloxifene had relatively lower incidence of
      new vertebral fractures. The SUCRA analysis showed that alendronate had better
      efficacy on improving BMD, risedronate could significantly decrease the incidence
      of fresh fracture and bazedoxifene was relatively safe. The available evidence
      suggested that alendronate and risedronate might be the superior choices for the
      treatment of PMO, while bazedoxifene was a comparatively safer option for
      patients.

PMID- 29227548
TI  - Resistance of oral cancer cells to 5-ALA-mediated photodynamic therapy.
AB  - Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma
      (OSCC) at early stages. Chemo and radio-resistance are frequently observed in
      OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was
      investigated the process of acquiring resistance to multiple cycles of PDT by
      using OSCC cells. We also analyzed the expression of anti-apoptotic proteins and
      those related to Akt/mTOR pathway. Sub-lethal doses of PDT were applied,
      consisting of a constant concentration of 5-aminolevulinic acid (5-ALA) (1 mM, 4
      h incubation) and increasing irradiation dose with LED (from 5.86 to 10.54 J/cm2
      ). Cell viability, migration capacity, intracellular expression of protoporphyrin
      IX (PpIX), mitochondrial density, and pro-survival proteins were investigated in
      PDT-resistant cells. Six OSCC cell generations resistant to PDT were isolated.
      The resistant cells exhibited a survival phenotype characterized by a reduction
      in the expression of endogenous PpIX, increase in mitochondrial density, increase
      in migration capacity, and up-regulation of p-NFkappaB, p-survivin, iNOS, p-Akt
      Ser473 , cyclin D1, p-mTOR Ser2481 , and p-mTOR Ser2448 . OSCC cells are able to
      survive doses of 5-ALA-PDT by reducing PpIX synthesis and activating signaling
      pathways related to the inhibition of apoptosis and improvement of cell
      proliferation. Further studies are necessary to confirm whether this PDT
      resistance phenotype can be clinically present, mainly in OSCC showing clinical
      recurrences after exposure to different PDT protocols.

PMID- 29227549
TI  - In Vitro Dissection of Autophagy.
AB  - Autophagy is an essential cellular process for bulk degradation of cytoplasmic
      components through the lysosome. Underlying this process is an intricate
      interaction between protein factors and the cell endomembrane system, leading to
      a gradual maturation of the autophagic membrane. This structure sequesters a
      portion of the cytoplasm by the formation of a double-membrane compartment called
      the autophagosome. The autophagosome then delivers the cargo to the lysosome to
      complete degradation. The molecular mechanism accounting for the generation of
      the autophagic membrane is a longstanding question. Here, a cell-free approach
      that has been established to understand the mechanism of early autophagic
      membrane generation is described. This system has provided insight into the
      membrane source of the autophagosome, the early protein-membrane associations,
      and the membrane remodeling that generates the autophagosomal precursors. The
      cell-free assay, in combination with other established approaches (e.g., cell
      imaging), will facilitate a deeper understanding of the mechanism of autophagy.
      (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227550
TI  - Live-Cell Visualization of Calcium Flux in Vibratome-Cut Thick Sections of Viable
      Tumor Tissue.
AB  - This unit outlines a live-cell imaging approach developed for visualization of
      intracellular calcium flux in human parathyroid tumors following stimulation of
      the calcium-sensing receptor (CASR), a class C G protein-coupled receptor (GPCR).
      The primary assay readout, intracellular calcium release induced by activation of
      the inositol triphosphate receptor, is potentially generalizable to multiple
      other GPCR signaling events that utilize this common downstream signal
      transduction pathway. Advantages of the approach include: (1) preservation of
      native tissue context and positional information, allowing direct visualization
      of intratumoral functional heterogeneity; (2) quantitative documentation of
      reactivity to a physiological stimulus in an experimentally tractable ex vivo
      system; and (3) generation of a dynamic, functional classifier of tumor
      biochemical behavior to augment static marker assessment. The technical steps are
      performed in three sequential phases: (1) viable tissue sectioning; (2)
      fluorophore loading and tissue immobilization; and (3) live-cell confocal
      microscopy. This versatile method provides a straightforward platform for
      functional characterization of human tumors. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227551
TI  - High Purity Isolation and Sensitive Quantification of Extracellular Vesicles
      Using Affinity to TIM4.
AB  - Almost all types of cells secrete extracellular vesicles (EVs), including
      exosomes and microvesicles. EVs carry various proteins, lipids, mRNAs, and
      microRNAs, and may participate in many aspects of physiological and
      pathophysiological processes. Various studies are currently being conducted to
      develop therapeutic and diagnostic methods targeting or utilizing EVs. Therefore,
      developing ideal methods for isolating and quantifying EVs is an active area of
      research. EVs express phosphatidylserine on their outer lipid bilayer. This unit
      describes an affinity-based method for isolating EVs using TIM4, which binds
      phosphatidylserine in a specific and calcium-dependent manner. EVs captured by
      TIM4 can be easily released by addition of a chelating agent, or can be retained
      for quantification by ELISA or flow cytometry. These methods enable the isolation
      of highly purified EVs and the sensitive quantification of EVs, which will
      accelerate EV research beyond what has been achievable with conventional methods.
      (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227552
TI  - Microfluidics-Assisted TIRF Imaging to Study Single Actin Filament Dynamics.
AB  - Dynamic assembly of actin filaments is essential for many cellular processes. The
      rates of assembly and disassembly of actin filaments are intricately controlled
      by regulatory proteins that interact with the ends and the sides of filaments and
      with actin monomers. TIRF-based single-filament imaging techniques have proven
      instrumental in uncovering mechanisms of actin regulation. In this unit, novel
      single-filament approaches using microfluidics-assisted TIRF imaging are
      described. These methods can be used to grow anchored actin filaments aligned in
      a flow, thus making the analysis much easier as compared to open flow cell
      approaches. The microfluidic nature of the system also enables rapid change of
      biochemical conditions and allows simultaneous imaging of a large number of actin
      filaments. Support protocols for preparing microfluidic chambers and purifying
      spectrin-actin seeds used for nucleating anchored filaments are also described.
      (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227553
TI  - Fluorescence Lifetime Imaging of a Caspase-3 Apoptosis Reporter.
AB  - Caspase-3 is a proteolytic enzyme that functions as a key effector in apoptotic
      cell death. Determining activity of caspase-3 provides critical information about
      cancer cell viability and response to treatment. To measure apoptosis in intact
      cells and living mice, a fluorescence imaging reporter that detects caspase-3
      activity by Forster resonance energy transfer (FRET) was used. Changes in FRET by
      fluorescence lifetime imaging microscopy (FLIM) were measured. Unlike FRET
      measurements based on fluorescence intensity, lifetime measurements are
      independent of reporter concentration and scattering of light in tissue, making
      FLIM a robust method for imaging in 3D environments. Apoptosis of breast cancer
      cells in 2D culture, spheroids, and in vivo murine breast tumor xenografts in
      response to a variety of genetic and pharmacologic methods implicated in
      apoptosis of cancer cells was studied. This approach for quantifying apoptosis of
      cancer cells is based on caspase-3 activity at single-cell resolution using FLIM.
      (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227554
TI  - Simple and Rapid Tissue Clearing Method for Three-Dimensional Histology of the
      Pancreas.
AB  - Previously, high-resolution three-dimensional imaging of a whole and intact
      pancreas was not possible, since light is scattered when it passes through cell
      compartments with different refractive indices. CLARITY is one of the tissue
      clearing techniques that has yielded success with the central nervous system. To
      preserve tissue integrity after delipidation, conventional protocols embed tissue
      in an acrylamide-based hydrogel, which involves the use of specialized equipment.
      Recently, we determined that the hydrogel-embedding step could be simplified and
      replaced by passive tissue fixation in 4% paraformaldehyde (PFA). The whole
      procedure is less time-consuming and less error-prone, and can be completed
      within a week, compared to conventional CLARITY protocols that may take weeks to
      complete. Here, the detailed stepwise procedures involved in the simplified
      CLARITY workflow are applied to the pancreas of wild-type and gene-knockout 6
      week old mice expressing green fluorescent protein (GFP) under the mouse insulin
      1 promoter (MIP-GFP). This technique could facilitate high-resolution, three
      dimensional imaging of pancreatic islets and comparison between different mouse
      genotypes under different disease and treatment conditions. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29227555
TI  - Combining Fluorescence and Bioluminescence Microscopy to Study the Series of
      Events from Cellular Signal Transduction to Gene Expression.
AB  - The molecular interactions and translocation of signal transduction factors in
      individual cells can be imaged by fluorescence microscopy. Alternatively,
      downstream promoter activity in single cells can be imaged by bioluminescence
      microscopy. However, the same stimuli can lead to different gene expression
      responses in individual cells. For this reason, it is desirable to simultaneously
      image signal transduction and gene expression events in the same cells. Here, we
      describe a method that combines fluorescence and bioluminescence microscopy to
      image protein kinase C (PKC) translocation from the cytosol to the plasma
      membrane and the expression of nuclear factor kappa-light polypeptide B (NF
      kappaB)-regulated genes. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29227556
TI  - Titanium Disulfide Coated Carbon Nanotube Hybrid Electrodes Enable High Energy
      Density Symmetric Pseudocapacitors.
AB  - While electrochemical supercapacitors often show high power density and long
      operation lifetimes, they are plagued by limited energy density. Pseudocapacitive
      materials, in contrast, operate by fast surface redox reactions and are shown to
      enhance energy storage of supercapacitors. Furthermore, several reported systems
      exhibit high capacitance but restricted electrochemical voltage windows, usually
      no more than 1 V in aqueous electrolytes. Here, it is demonstrated that
      vertically aligned carbon nanotubes (VACNTs) with uniformly coated,
      pseudocapacitive titanium disulfide (TiS2 ) composite electrodes can extend the
      stable working range to over 3 V to achieve a high capacitance of 195 F g-1 in an
      Li-rich electrolyte. A symmetric cell demonstrates an energy density of 60.9 Wh
      kg-1 -the highest among symmetric pseudocapacitors using metal oxides, conducting
      polymers, 2D transition metal carbides (MXene), and other transition metal
      dichalcogenides. Nanostructures prepared by an atomic layer
      deposition/sulfurization process facilitate ion transportation and surface
      reactions to result in a high power density of 1250 W kg-1 with stable operation
      over 10 000 cycles. A flexible solid-state supercapacitor prepared by
      transferring the TiS2 -VACNT composite film onto Kapton tape is demonstrated to
      power a 2.2 V light emitting diode (LED) for 1 min.

PMID- 29227557
TI  - Building Organic/Inorganic Hybrid Interphases for Fast Interfacial Transport in
      Rechargeable Metal Batteries.
AB  - We report a facile in situ synthesis that utilizes readily accessible SiCl4 cross
      linking chemistry to create durable hybrid solid-electrolyte interphases (SEIs)
      on metal anodes. Such hybrid SEIs composed of Si-interlinked OOCOR molecules that
      host LiCl salt exhibit fast charge-transfer kinetics and as much as five-times
      higher exchange current densities, in comparison to their spontaneously formed
      analogues. Electrochemical analysis and direct optical visualization of Li and Na
      deposition in symmetric Li/Li and Na/Na cells show that the hybrid SEI provides
      excellent morphological control at high current densities (3-5 mA cm-2 ) for Li
      and even for notoriously unstable Na metal anodes. The fast interfacial transport
      attributes of the SEI are also found to be beneficial for Li-S cells and stable
      electrochemical cycling was achieved in galvanostatic studies at rates as high as
      2 C. Our work therefore provides a promising approach towards rational design of
      multifunctional, elastic SEIs that overcome the most serious limitations of
      spontaneously formed interphases on high-capacity metal anodes.

PMID- 29227558
TI  - RNA sequencing identifies gene regulatory networks controlling extracellular
      matrix synthesis in intervertebral disk tissues.
AB  - : Degenerative disk disease of the spine is a major cause of back pain and
      disability. Optimization of regenerative medical therapies for degenerative disk
      disease requires a deep mechanistic understanding of the factors controlling the
      structural integrity of spinal tissues. In this investigation, we sought to
      identify candidate regulatory genes controlling extracellular matrix synthesis in
      spinal tissues. To achieve this goal we performed high throughput next generation
      RNA sequencing on 39 annulus fibrosus and 21 nucleus pulposus human tissue
      samples. Specimens were collected from patients undergoing surgical discectomy
      for the treatment of degenerative disk disease. Our studies identified
      associations between extracellular matrix genes, growth factors, and other
      important regulatory molecules. The fibrous matrix characteristic of annulus
      fibrosus was associated with expression of the growth factors platelet derived
      growth factor beta (PDGFB), vascular endothelial growth factor C (VEGFC), and
      fibroblast growth factor 9 (FGF9). Additionally we observed high expression of
      multiple signaling proteins involved in the NOTCH and WNT signaling cascades.
      Nucleus pulposus extracellular matrix related genes were associated with the
      expression of numerous diffusible growth factors largely associated with the
      transforming growth signaling cascade, including transforming factor alpha
      (TGFA), inhibin alpha (INHA), inhibin beta A (INHBA), bone morphogenetic proteins
      (BMP2, BMP6), and others. CLINICAL SIGNIFICANCE: this investigation provides
      important data on extracellular matrix gene regulatory networks in disk tissues.
      This information can be used to optimize pharmacologic, stem cell, and tissue
      engineering strategies for regeneration of the intervertebral disk and the
      treatment of back pain. (c) 2017 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 36:1356-1369, 2018.

PMID- 29227560
TI  - Enhancing Van der Waals Interactions of Functionalized UiO-66 with Non-polar
      Adsorbates: The Unique Effect of para Hydroxyl Groups.
AB  - UiO-66 is a highly stable metal-organic framework (MOF) that has garnered
      interest for many adsorption applications. For small, nonpolar adsorbates,
      physisorption is dominated by weak Van der Waals interactions limiting the
      adsorption capacity. A common strategy to enhance the adsorption properties of
      isoreticular MOFs, such as UiO-66, is to add functional groups to the organic
      linker. Low and high pressure O2 isotherms were measured on UiO-66 MOFs
      functionalized with electron donating and withdrawing groups. It was found that
      the electron donating effects of -NH2 , -OH, and -OCF3 groups enhance the uptake
      of O2 . Interestingly, a significant enhancement in both the binding energy and
      adsorption capacity of O2 was observed for UiO-66-(OH)2 -p, which has two -OH
      groups para from one another. Density functional theory (DFT) simulations were
      used to calculate the binding energy of oxygen to each MOF, which trended with
      the adsorption capacity and agreed well with the heats of adsorption calculated
      from the Toth model fit to multi-temperature isotherms. DFT simulations also
      determined the highest energy binding site to be on top of the electron pi-cloud
      of the aromatic ring of the ligand, with a direct trend of the binding energy
      with low pressure adsorption capacity. Uniquely, DFT found that oxygen molecules
      adsorbed to UiO-66-(OH)2 -p prefer to align parallel to the -OH groups on the
      aromatic ring. Similar effects for the electron donation of the functional groups
      were observed for the low pressure adsorption of N2 , CH4 , and CO2 .

PMID- 29227559
TI  - Magnetic resonance measurements of tissue quantity and quality using T2 *
      relaxometry predict temporal changes in the biomechanical properties of the
      healing ACL.
AB  - : The purpose of this study was to develop a magnetic resonance T2 * relaxometry
      based multiple linear regression model to predict the structural properties of
      the healing anterior cruciate ligament (ACL) over a 24-week healing period
      following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a
      regression model based on ACL sub-volumes containing short and long T2 *
      relaxation times would outperform a competing model based on sub-volumes of short
      T2 * relaxation times only; and (ii) that an optimized regression model would be
      capable of predicting ACL structural properties between 6 and 24 weeks post
      repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks
      after ACL repair. The structural properties of the ACLs were determined from
      tensile failure tests. Four multiple linear regression models of increasing
      complexity were fitted to the data. Akaike Information Criterion values and Bland
      Altman tests were used to compare model performance and to test the hypotheses.
      The structural properties predicted from the multiple linear regression model
      that was based on the change in ACL sub-volumes of both the short and long T2 *
      relaxation times over the healing period were in closest agreement to the
      measured values, suggesting that the amounts of both organized and disorganized
      collagen, and the change in these quantities over time, are required to predict
      the structural properties of healing ACLs accurately. CLINICAL SIGNIFICANCE: our
      time-specific, T2 *-based regression model may allow us to estimate the
      structural properties of ACL repairs in vivo longitudinally. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1701-1709,
      2018.

PMID- 29227561
TI  - Green Synthesis of a New Al-MOF Based on the Aliphatic Linker Mesaconic Acid:
      Structure, Properties and In Situ Crystallisation Studies of Al-MIL-68-Mes.
AB  - A new aluminium metal-organic framework (MOF), based on the short aliphatic
      linker molecule mesaconic acid (H2 Mes; methylfumaric acid) is reported. Al-MIL
      68-Mes with composition [Al(OH)(O2 C-C3 H4 -CO2 )]?n H2 O is obtained after short
      reaction times of 45 minutes under mild, aqueous synthesis conditions (95 
      degrees C). It exhibits a kagome-like framework structure with large hexagonal,
      and small trigonal channels (diameters of ~6 and ~2 A, respectively) and a
      specific surface area of SBET ~1040 m2  g-1 (VMIC =0.42 cm3  g-1 ). A sigmoidal
      vapour sorption isotherm for water, and uptakes of water and methanol above 30
      wt. % were observed. Al-MIL-68-Mes is stable against water ad-/desorption and its
      thermal stability is 350  degrees C in air. The proton conductivity for the
      hydrated MOF showed values up to 1.1*10-5  S cm at 130  degrees C and 100 %
      relative humidity, which exceeds the values observed for the non-hydrated
      compound by up to four orders of magnitude. Using synchrotron radiation the
      crystallisation of the MOF by in situ PXRD was also studied at temperatures from
      80 to 100  degrees C. Kinetic evaluation revealed that the induction periods and
      crystallization times vary depending on the synthesis batch, but the rate
      limiting steps are consistently observed.

PMID- 29227562
TI  - Crosstalk between substance P and calcitonin gene-related peptide during
      heterotopic ossification in murine Achilles tendon.
AB  - Heterotopic ossification (HO) is abnormal bone formation within soft tissue,
      usually predisposed by neurogenic or musculoskeletal trauma. Inflammation
      resulting from trauma is considered to be the main trigger for HO by eliciting
      changes within the injury site, including elevation of bone morphogenetic
      proteins (BMPs). Recent research, however, has also associated changes in sensory
      neuropeptide expression with HO. Substance P (SP) and calcitonin gene-related
      peptide (CGRP) are two of those neuropeptides that have been implicated with
      various aspects of HO, including regulation of inflammation and BMP signaling.
      Despite discoveries associating SP and CGRP with soft tissue HO, it remains
      unclear whether SP and CGRP have a direct role in the induction of HO. Here, we
      investigated the effect of SP and CGRP in vivo with the aid of inkjet-based
      biopatterning technology to controllably deliver these neuropeptides onto a
      murine Achilles tendon. While we did not observe any significant effect with
      CGRP, SP alone promoted HO in vivo with increased expression of BMP2. Remarkably,
      when SP and CGRP were delivered together, CGRP counteracted the effect of SP and
      essentially blocked SP-induced HO. This report contributes to the understanding
      of the complex problem of HO pathophysiology and warrants more study to better
      elucidate the interplay between SP and CGRP in the induction of HO. (c) 2017
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:1444-1455, 2018.

PMID- 29227563
TI  - Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in
      human skin and tissue-engineered skin equivalents.
AB  - CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3
      subfamily collectively involved in the biotransformation of approximately 30% of
      all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin, yet
      knowledge of their protein expression and function is lacking. In this study, we
      observed gene and protein expression of CYP3A4/5 in both human skin and tissue
      engineered skin equivalents (TESEs), and enzyme activity was detected using the
      model substrate benzyl-O-methyl-cyanocoumarin. Mass spectrometric analysis of
      TESE lysates following testosterone application revealed a time-dependent
      increase in metabolite production, confirming the functional expression of these
      enzymes in skin.

PMID- 29227564
TI  - Novel mold-resistant building materials impregnated with thermally reduced nano
      silver.
AB  - In this study, we evaluated the long-term antifungal effectiveness of 3 types of
      interior building materials (gypsum board [GB], cement board [CB], and softwood
      plywood [S-PW]) impregnated with thermally reduced silver nanoparticles supported
      by titanium dioxide (AgNPs/TiO2 ) under 95% relative humidity for 4 weeks.
      AgNPs/TiO2 was synthesized at 2 thermal reduction temperatures (TRTs, 120 and 200
      degrees C) with 2 different AgNP weight percentages (2 and 5 wt%). Four different
      silver-loading levels (SLLs, 0.025, 0.05, and 0.5 MUg/cm2 and the critical
      concentration required to inhibit fungal growth on agar plates) and 3 fungal
      species (Aspergillus niger, Penicillium spinulosum, and Stachybotrys chartarum)
      were used in the experiments. Higher temperature reduced more ionic Ag+ to
      metallic Ag0 and increased the dispersion of Ag on TiO2 surface. The 200 degrees
      C thermally reduced AgNPs/TiO2 demonstrated excellent antifungal efficiency: Mold
      growth was almost completely inhibited for 28 days at the low SLL of 0.5 MUg/cm2
      . Additionally, AgNPs/TiO2 exhibited higher antifungal activity on GB and CB than
      on S-PW. The stepwise regression results indicated that the TRT of AgNPs/TiO2
      (beta = -0.739 to -0.51), the SLL (beta = -0.477 to -0.269), and the Ag0 level in
      the AgNPs (beta = -0.379 to -0.136) were the major factors influencing antifungal
      activity and TRT might be the most significant one.

PMID- 29227565
TI  - Limited utility of routine chest X-ray in initial evaluation of neutropenic fever
      in patients with haematological diseases undergoing chemotherapy.
AB  - BACKGROUND: Routine chest X-ray (CXR) is recommended for neutropenic fever (NF)
      management however its role is relatively understudied in haematology patients.
      AIM: To investigate the utility of CXR in the diagnosis and management of
      patients with haematological conditions complicated by NF. METHODS:
      Retrospective, single-centre analysis of haematology patients admitted with NF
      between January 2011 and December 2015. Baseline demographics, treatment details
      and outcomes were collected from electronic patient records. CXR underwent
      independent radiology review. Primary endpoints were a proportion of NF episodes
      in which CXR detected a probable chest infection in the absence of respiratory
      symptoms/signs and/or resulted in a change in antibiotic management. RESULTS:
      Four hundred and thirty-five episodes were identified; CXR was performed in 75%
      of patients (65% within 2 days of NF). In 4 of 164 (2.4%) asymptomatic patients,
      CXR was consistent with infection, in contrast to 19 of 119 (16%) patients with
      clinical signs of respiratory infection. Only 3 of 283 (1.1%) CXR resulted in a
      change to antibiotics. CXR consistent with infection was not associated with
      increased mortality or increased admission length, although there was an
      association with intensive care unit admission (odds ratios: 7.61, 95% confidence
      interval: 2.04-28.31). CONCLUSION: In haematology patients with NF, CXR rarely
      detected chest infection or changed management in patients with no respiratory
      symptoms or signs. CXR in our institution is no longer part of routine assessment
      of NF in the absence of these features.

PMID- 29227566
TI  - A Bioresistant Nitroxide Spin Label for In-Cell EPR Spectroscopy: In Vitro and In
      Oocytes Protein Structural Dynamics Studies.
AB  - Approaching protein structural dynamics and protein-protein interactions in the
      cellular environment is a fundamental challenge. Owing to its absolute
      sensitivity and to its selectivity to paramagnetic species, site-directed spin
      labeling (SDSL) combined with electron paramagnetic resonance (EPR) has the
      potential to evolve into an efficient method to follow conformational changes in
      proteins directly inside cells. Until now, the use of nitroxide-based spin labels
      for in-cell studies has represented a major hurdle because of their short
      persistence in the cellular context. The design and synthesis of the first
      maleimido-proxyl-based spin label (M-TETPO) resistant towards reduction and being
      efficient to probe protein dynamics by continuous wave and pulsed EPR is
      presented. In particular, the extended lifetime of M-TETPO enabled the study of
      structural features of a chaperone in the absence and presence of its binding
      partner at endogenous concentration directly inside cells.

PMID- 29227567
TI  - Canine hip dysplasia: A natural animal model for human developmental dysplasia of
      the hip.
AB  - Developmental dysplasia of the hip (DDH) in humans is a common condition that is
      associated with hip pain, functional limitations, and secondary osteoarthritis
      (OA). Surgical treatment of DDH has improved in the last decade, allowing
      excellent outcomes at short- and mid-term follow-up. Still, the etiology,
      mechanobiology, and pathology underlying this disease are not well understood. A
      pre-clinical animal model of DDH could help advance the field with a deeper
      understanding of specific pathways that initiate hip joint degeneration secondary
      to abnormal biomechanics. An animal model would also facilitate different
      interventional treatments that could be tested in a rigorous and controlled
      environment. The dog model exhibits several important characteristics that make
      it valuable as a pre-clinical animal model for human DDH. Dogs are naturally
      prone to develop canine hip dysplasia (CHD), which is treated in a similar manner
      as in humans. Comparable to human DDH, CHD is considered a pre-OA disease; if
      left untreated it will progress to OA. However, progression to OA is
      significantly faster in dogs than humans, with progression to OA within 1-2 years
      of age, associated with their shorter life span compared to humans. Animal
      studies could potentially reveal the underlying biochemical pathway(s), which can
      inform refined treatment modalities and provide opportunities for new treatment
      and prevention targets. Herein, we review the similarities and differences
      between the two species and outline the argument supporting CHD as an appropriate
      pre-clinical model of human DDH. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:1807-1817, 2018.

PMID- 29227568
TI  - The effect of small dose of topiroxostat on serum uric acid in patients receiving
      hemodialysis.
AB  - INTRODUCTION: Topiroxostat, a recently developed xanthine oxidase inhibitor, is
      expected to have fewer adverse effects than allopurinol because it has different
      mechanism of action from alloprinol. However, its dosage, usage and safety have
      not been established in patients with impaired renal function or those undergoing
      dialysis at the development since no studies was conducted in these patients.
      METHODS: Cross over clinical trial using 3 months of allopurinol and topiroxostat
      on 27 maintain Japanese HD patients were carried out. The effects on oxidative
      stress status of both drugs were also evaluated by measuring oxidation reduction
      potential. FINDINGS: Twenty-five of twenty-seven patients completed study. The
      mean serum uric acid levels in the topiroxostat-treated arm was significantly
      lower than it in the allopurinol-treated arm time-dependently (P < 0.0001).
      Corrected oxidative stress ratio defined as biological antioxidant
      potential/diacron reactive oxygen metabolites was significantly increased in
      topiroxostat-arm (*P = 0.0035), but not in allopurinol-arm (P = 0.1429). No
      significant difference was seen in diacron reactive oxygen metabolites,
      biological antioxidant potential, static oxidation-reduction potential, and
      capacity oxidation-reduction potential between pre and post treatment of both
      drugs. DISCUSSION: It is suggested that a low dose of topiroxostat decreased
      serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving
      hemodialysis.

PMID- 29227569
TI  - New diagnosis of bullous pemphigoid after withdrawal of immunosuppressive therapy
      in a failed renal transplant recipient on hemodialysis.
AB  - The occurrence of the autoimmune blistering disease, bullous pemphigoid (BP), in
      patients with failed renal allograft is rare and the few reported cases suggest
      various provocative factors without reaching a consensus. Here we report the case
      of a patient presenting with bullous lesions soon after the complete
      discontinuation of immunosuppressant therapy following renal allograft failure.
      Skin biopsy confirmed the diagnosis of BP. Administration of systemic
      corticosteroid controlled the occurrence of BP lesions in our patient. Increased
      clinical suspicion is warranted in cases of patients with renal transplant
      failure, since withdrawal of the immunosuppressant therapy could lead to
      unmasking the underlying autoimmune skin disease.

PMID- 29227570
TI  - High-molecular-weight kininogen: breaking bad in lethal endotoxemia.

PMID- 29227571
TI  - Comparative effectiveness of metformin monotherapy in extended release and
      immediate release formulations for the treatment of type 2 diabetes in treatment
      naive Chinese patients: Analysis of results from the CONSENT trial.
AB  - AIMS: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by
      gastrointestinal (GI) adverse events (AEs), resulting in treatment
      discontinuation. We investigated whether once-daily metformin extended release
      (XR) is superior in terms of GI tolerability, with non-inferior efficacy,
      compared with thrice-daily metformin immediate release (IR) in treatment-naive
      Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label,
      randomized, multicentre, phase IV interventional study enrolled Chinese T2DM
      patients to receive either metformin XR or metformin IR with a 2-week screening
      period, a 16-week treatment period and a 2-week follow-up period without
      treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR
      vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change
      from baseline to week 16 and the superiority of GI tolerability for metformin XR
      vs metformin IR. RESULTS: Overall, 532 patients were randomized to metformin IR
      (n = 267) or metformin XR (n = 265). The HbA1c LSM change was -1.61% and -1.58%
      in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], 
      0.10, 0.17). Incidences of drug-related AEs were 26.5% (n = 66) in the metformin
      IR-only group and 32.2% (n = 85) in the metformin XR-only group, and GI AEs were
      23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60,
      5.56). The treatment difference met the predefined non-inferiority upper CI
      margin of 0.4% in HbA1c. CONCLUSIONS: Metformin XR was non-inferior to metformin
      IR for the LSM change in HbA1c from baseline to week 16 and not superior to
      metformin IR for overall GI AE incidence during treatment of Chinese T2DM
      patients.

PMID- 29227572
TI  - Factors associated with serum magnesium and vascular stiffness in maintenance
      hemodialysis patients.
AB  - INTRODUCTION: We evaluated the associated factors of serum magnesium in patients
      on maintenance hemodialysis (MHD). Furthermore, we evaluated the relationship
      between low serum magnesium and arteriosclerosis in these patients. METHODS: In
      129 patients on MHD, we evaluated the blood levels of magnesium, brachial-ankle
      pulse wave velocity (ba-PWV), ankle-brachial index (ABI), and intima-media
      thickness of the common carotid artery (IMT). FINDINGS: In MHD patients, the
      serum level of magnesium was significantly correlated with age, calcium, TNF
      alpha, albumin, and ba-PWV but not with ABI or IMT. In the multiple regression
      analysis, albumin (P = 0.0001, beta = 0.31) and calcium (P = 0.029, beta = 0.18)
      were selected as significant predictors of the magnesium level in MHD patients.
      Furthermore, the serum level of magnesium, as well as systolic blood pressure (P
      = 0.0001, beta = 0.32) and age (P = 0.005, beta = 0.25), were selected as
      significant (P = 0.012, beta = -0.22) predictors of ba-PWV in MHD patients.
      DISCUSSION: In MHD patients, the serum magnesium level was associated with the
      serum levels of calcium and albumin. Furthermore, a low serum magnesium level in
      MHD patients was associated with the index of vascular stiffness.

PMID- 29227574
TI  - Light treatments of nail fungal infections.
AB  - Nail fungal infections are notoriously persistent and difficult to treat which
      can lead to severe health impacts, particularly in the immunocompromized. Current
      antifungal treatments, including systemic and topical drugs, are prolonged and do
      not effectively provide a complete cure. Severe side effects are also associated
      with systemic antifungals, such as hepatotoxicity. Light treatments of
      onychomycosis are an emerging therapy that has localized photodynamic,
      photothermal or photoablative action. These treatments have shown to be an
      effective alternative to traditional antifungal remedies with comparable or
      better cure rates achieved in shorter times and without systemic side effects.
      This report reviews significant clinical and experimental studies in the field,
      highlighting mechanisms of action and major effects related to light therapy; in
      particular, the impact of light on fungal genetics.

PMID- 29227575
TI  - Effect of single-dose DPP-4 inhibitor sitagliptin on beta-cell function and
      incretin hormone secretion after meal ingestion in healthy volunteers and drug
      naive, well-controlled type 2 diabetes subjects.
AB  - To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on
      glucose-standardized insulin secretion and beta-cell glucose sensitivity after
      meal ingestion, 12 healthy and 12 drug-naive, well-controlled type 2 diabetes
      (T2D) subjects (mean HbA1c 43 mmol/mol, 6.2%) received sitagliptin (100 mg) or
      placebo before a meal (525 kcal). beta-cell function was measured as the insulin
      secretory rate at a standardized glucose concentration and the beta-cell glucose
      sensitivity (the slope between glucose and insulin secretory rate). Incretin
      levels were also monitored. Sitagliptin increased standardized insulin secretion,
      in both healthy and T2D subjects, compared to placebo, but without increasing
      beta-cell glucose sensitivity. Sitagliptin also increased active glucose
      dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)
      and reduced total (reflecting the secretion) GIP, but not total GLP-1 levels. We
      conclude that a single dose of DPP-4 inhibition induces dissociated effects on
      different aspects of beta-cell function and incretin hormones after meal
      ingestion in both healthy and well-controlled T2D subjects.

PMID- 29227577
TI  - Management of pain in end-stage renal disease patients: Short review.
AB  - Pain management in end stage renal disease (ESRD) patients is a complex and
      challenging task to accomplish, and effective pain and symptom control improves
      quality of life. Pain is prevalent in more than 50% of hemodialysis patients and
      up to 75% of these patients are treated ineffectively due to its poor recognition
      by providers. A good history for PQRST factors and intensity assessment using
      visual analog scale are the initial steps in the management of pain followed by
      involvement of palliative care, patient and family counseling, discussion of
      treatment options, and correction of reversible causes. First line should be
      conservative management such as exercise, massage, heat/cold therapy,
      acupuncture, meditation, distraction, music therapy, and cognitive behavioral
      therapy. Analgesics are introduced according to WHO guidelines (by the mouth, by
      the clock, by the ladder, for the individual, and attention to detail) using
      three-step analgesic ladder model. Neuropathic pain can be controlled by
      gabapentin and pregabalin. Substitution/addition of opioid analgesics are
      indicated if pain control is not optimal. Commonly used opioids in ESRD patients
      are tramadol, oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine.
      Methadone, fentanyl, and buprenorphine are the ideal analgesics in ESRD. However,
      complex pain syndrome requires multidrug analgesic regimen comprising opioids,
      non-opioids, and adjuvant medication, which should be individualized to the
      patient to achieve adequate pain control.

PMID- 29227576
TI  - Microscopic investigation of" topically applied nanoparticles for molecular
      imaging of fresh tissue surfaces.
AB  - Previous studies have shown that functionalized nanoparticles (NPs) topically
      applied on fresh tissues are able to rapidly target cell-surface protein
      biomarkers of cancer. Furthermore, studies have shown that a paired-agent
      approach, in which an untargeted NP is co-administered with a panel of targeted
      NPs, controls for the nonspecific behavior of the NPs, enabling quantitative
      imaging of biomarker expression. However, given the complexities in nonspecific
      accumulation, diffusion, and chemical binding of targeted NPs in tissues, studies
      are needed to better understand these processes at the microscopic scale. Here,
      fresh tissues were stained with a paired-agent approach, frozen, and sectioned to
      image the depth-dependent accumulation of targeted and untargeted NPs. The ratio
      of targeted-to-untargeted NP concentrations-a parameter used to distinguish
      between tumor and benign tissues-was found to diminish with increasing NP
      diffusion depths due to nonspecific accumulation and poor washout. It was then
      hypothesized and experimentally demonstrated that larger NPs would exhibit less
      diffusion below tissue surfaces, enabling higher targeted-to-untargeted NP
      ratios. In summary, these methods and investigations have enabled the design of
      NP agents with improved sensitivity and contrast for rapid molecular imaging of
      fresh tissues.

PMID- 29227573
TI  - Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other"
      Next Steps.
AB  - As psychiatric genetics enters an era where gene identification is finally
      yielding robust, replicable genetic associations and polygenic risk scores, it is
      important to consider next steps and delineate how that knowledge will be applied
      to ultimately ameliorate suffering associated with substance use and psychiatric
      disorders. Much of the post-genome-wide association study discussion has focused
      on the potential of genetic information to elucidate the underlying biology and
      use this information for the development of more effective pharmaceutical
      treatments. In this review we focus on additional areas of research that should
      follow gene identification. By taking genetic findings into longitudinal,
      developmental studies, we can map the pathways by which genetic risk manifests
      across development, elucidating the early behavioral manifestations of risk, and
      studying how various environments and interventions moderate that risk across
      developmental stages. The delineation of risk across development will advance our
      understanding of mechanism, sex differences and risk and resilience processes in
      different racial/ethnic groups. Here, we review how the extant twin study
      literature can be used to guide these efforts. Together, these new lines of
      research will enable us to develop more informed, tailored prevention and
      intervention efforts.

PMID- 29227578
TI  - Insulin secretion predicts the response to therapy with exenatide plus
      pioglitazone, but not to basal/bolus insulin in poorly controlled T2DM patients:
      Results from the Qatar study.
AB  - The present study aims to identify predictors for response to combination therapy
      with pioglitazone plus exenatide vs basal/bolus insulin therapy in T2DM patients
      who are poorly controlled with maximum/near-maximum doses of metformin plus a
      sulfonylurea. Participants in the Qatar study received a 75-g OGTT with
      measurement of plasma glucose, insulin and C-peptide concentration at baseline
      and were then randomized to receive either treatment with pioglitazone plus
      exenatide or basal/bolus insulin therapy for one year. Insulin secretion measured
      with plasma C-peptide concentration during the OGTT was the strongest predictor
      of response to combination therapy (HbA1c <= 7.0%) with pioglitazone plus
      exenatide. A 54% increase in 2-hour plasma C-peptide concentration above the
      fasting level identified subjects who achieved the glycaemic goal (HbA1c < 7.0%)
      with 82% sensitivity and 79% specificity. Only baseline HbA1c was a predictor of
      response to basal/bolus insulin therapy. Thus, the increment in 2-hour plasma C
      peptide concentration above the fasting level provides a useful tool to identify
      poorly controlled T2DM patients who can achieve glycaemic control without insulin
      therapy, and thereby, can be used to individualize antihyperglycaemic therapy in
      poorly controlled T2DM patients.

PMID- 29227579
TI  - Obesity/type 2 diabetes increases inflammation, periosteal reactive bone
      formation, and osteolysis during Staphylococcus aureus implant-associated bone
      infection.
AB  - Obese and type 2 diabetic (T2D) patients have a fivefold increased rate of
      infection following placement of an indwelling orthopaedic device. Though implant
      infections are associated with inflammation, periosteal reactive bone formation,
      and osteolysis, the effect of obesity/T2D on these complicating factors has not
      been studied. To address this question, C57BL/6J mice were fed a high fat diet
      (60% Kcal from fat) to induce obesity/T2D, or a control diet (10% Kcal from fat)
      for 3 months, and challenged with a transtibial pin coated with a bioluminescent
      USA300 strain of S. aureus. In the resulting infected bone, obesity/T2D was
      associated with increased S. aureus proliferation and colony forming units. RNA
      sequencing of the infected tibiae on days 7 and 14 revealed an increase in 635
      genes in obese/T2D mice relative to controls. Pathways associated with
      ossification, angiogenesis, and immunity were enriched. MicroCT and histology on
      days 21 and 35 demonstrated significant increased periosteal reactive bone
      formation in infected obese/T2D mice versus infected controls (p < 0.05). The
      enhanced periosteal bone formation was associated with increased osteoblastic
      activity and robust endochondral ossification, with persistant cartilage on day
      21 that was only observed in infected obesity/T2D. Osteolysis and osteoclast
      numbers in obesity/T2D were also significantly increased versus infected controls
      (p < 0.05). Consistent with an up-regulated immune transcriptome, macrophages
      were more abundant within both the periosteum and the new reactive bone of
      obese/T2D mice. In conclusion, we find that implant-associated S. aureus
      osteomyelitis in obesity/T2D is associated with increased inflammation, reactive
      bone formation, and osteolysis. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:1614-1623, 2018.

PMID- 29227580
TI  - Electrodeposition of Nickel Nanoparticles for the Alkaline Hydrogen Evolution
      Reaction: Correlating Electrocatalytic Behavior and Chemical Composition.
AB  - Ni nanoparticles (NPs) consisting of Ni, NiO, and Ni(OH)2 were formed on Ti
      substrates by electrodeposition as electrocatalysts for the hydrogen evolution
      reaction (HER) in alkaline solution. Additionally, the deposition parameters
      including the potential range and the scan rate were varied, and the resulting
      NPs were investigated by scanning electron microscopy and X-ray photoelectron
      spectroscopy. The chemical composition of the NPs changed upon using different
      conditions, and it was found that the catalytic activity increased with an
      increase in the amount of NiO. From these data, optimized NPs were synthesized;
      the best sample showed an onset potential of approximately 0 V and an
      overpotential of 197 mV at a cathodic current density of 10 mA cm-2 as well as a
      small Tafel slope of 88 mV dec-1 in 1 m KOH, values that are comparable to those
      of Pt foil. These NPs consist of approximately 25 % Ni and Ni(OH)2 each, as well
      as approximately 50 % NiO. This implies that to obtain a successful HER
      electrocatalyst, active sites with differing compositions have to be close to
      each other to promote the different reaction steps. Long-time measurements (30 h)
      showed almost complete transformation of the highly active catalyst compound
      consisting of Ni0 , NiO, and Ni(OH)2 into the less active Ni(OH)2 phase.
      Nevertheless, the here-employed electrodeposition of nonprecious metal/metal
      oxide combination compounds represents a promising alternative to Pt-based
      electrocatalysts for water reduction to hydrogen.

PMID- 29227582
TI  - Role of the sodium-hydrogen exchanger in mediating the renal effects of drugs
      commonly used in the treatment of type 2 diabetes.
AB  - Diabetes is characterized by increased activity of the sodium-hydrogen exchanger
      (NHE) in the glomerulus and renal tubules, which contributes importantly to the
      development of nephropathy. Despite the established role played by the exchanger
      in experimental studies, it has not been specifically targeted by those seeking
      to develop novel pharmacological treatments for diabetes. This review
      demonstrates that many existing drugs that are commonly prescribed to patients
      with diabetes act on the NHE1 and NHE3 isoforms in the kidney. This action may
      explain their effects on sodium excretion, albuminuria and the progressive
      decline of glomerular function in clinical trials; these responses cannot be
      readily explained by the influence of these drugs on blood glucose. Agents that
      may affect the kidney in diabetes by virtue of an action on NHE include: (1)
      insulin and insulin sensitizers; (2) incretin-based agents; (3) sodium-glucose
      cotransporter 2 inhibitors; (4) antagonists of the renin-angiotensin system
      (angiotensin converting-enzyme inhibitors, angiotensin receptor blockers and
      angiotensin receptor neprilysin inhibitors); and (5) inhibitors of aldosterone
      action and cholesterol synthesis (spironolactone, amiloride and statins). The
      renal effects of each of these drug classes in patients with type 2 diabetes may
      be related to a single shared biological mechanism.

PMID- 29227581
TI  - Aging of lymphoid organs: Can photobiomodulation reverse age-associated thymic
      involution via stimulation of extrapineal melatonin synthesis and bone marrow
      stem cells?
AB  - Thymic atrophy and the subsequent reduction in T-cell production are the most
      noticeable age-related changes affecting lymphoid organs in the immune system. In
      fact, thymic involution has been described as "programmed aging." New therapeutic
      approaches, such as photobiomodulation (PBM), may reduce or reverse these
      changes. PBM (also known as low-level laser therapy) involves the delivery of non
      thermal levels of red or near-infrared light that are absorbed by mitochondrial
      chromophores, in order to prevent tissue death and stimulate healing and
      regeneration. PBM may reverse or prevent thymic involution due to its ability to
      induce extrapineal melatonin biosynthesis via cyclic adenosine monophosphate
      (AMP) or NF-kB activation, or alternatively by stimulating bone marrow stem cells
      that can regenerate the thymus. This perspective puts forward a hypothesis that
      PBM can alter thymic involution, improve immune functioning in aged people and
      even extend lifespan.

PMID- 29227583
TI  - Single point mutation on the gene encoding dysbindin results in recognition
      deficits.
AB  - The dystrobrevin-binding protein 1 (DTNBP1) gene is a candidate risk factor for
      schizophrenia and has been associated with cognitive ability in both patient
      populations and healthy controls. DTNBP1 encodes dysbindin protein, which is
      localized to synaptic sites and is reduced in the prefrontal cortex and
      hippocampus of patients with schizophrenia, indicating a potential role in
      schizophrenia etiology. Most studies of dysbindin function have focused on the
      sandy (sdy) mice that lack dysbindin protein and have a wide range of
      abnormalities. In this study, we examined dysbindin salt and pepper (spp) mice
      that possess a single point mutation on the Dtnbp1 gene predicted to reduce, but
      not eliminate, dysbindin expression. By western blot analysis, we found that spp
      homozygous (spp -/-) mutants had reduced dysbindin and synaptosomal-associated
      protein 25 (SNAP-25) in the prefrontal cortex, but unaltered levels in
      hippocampus. Behaviorally, spp mutants performed comparably to controls on a wide
      range of tasks assessing locomotion, anxiety, spatial recognition and working
      memory. However, spp -/- mice had selective deficits in tasks measuring novel
      object recognition and social novelty recognition. Our results indicate that
      reduced dysbindin and SNAP-25 protein in the prefrontal cortex of spp -/- is
      associated with selective impairments in recognition processing. These spp mice
      may prove useful as a novel mouse model to study cognitive deficits linked to
      dysbindin alterations. Our findings also suggest that aspects of recognition
      memory may be specifically influenced by DTNBP1 single nucleotide polymorphisms
      or risk haplotypes in humans and this connection should be further investigated.

PMID- 29227585
TI  - Effect of ultrafiltration on placental-fetal blood flow in pregnancy of woman
      undergoing chronic hemodialysis.
AB  - INTRODUCTION: Patient who was undergoing hemodialysis (HD) thrice weekly usually
      gain 1 to 4 kg of weight in interdialytic period, mainly due to fluid
      accumulation by ingestion of water. Ultrafiltration (UF) during HD will be need
      to remove fluid excess to avoid severe medical complications secondary to fluid
      overload. However, in pregnant woman UF can increase the episodes of
      intradialytic hypotension which may lead to placental ischemic injury and
      predispose to fetal distress. There is little information about safe fluid amount
      withdrawn by UF during pregnancy. METHODS: We prospectively study by obstetric
      Doppler ultrasonography the fluxometric parameters: pulsatility index (PI) and
      resistance index (RI) of fetal middle cerebral, uterine, and umbilical artery
      obtained at the beginning and the end of HD session, the acute and chronic effect
      of UF on placenta and fetus blood flow, as well as the fetal outcome in 1
      pregnant woman on chronic HD. FINDINGS: We did not observe any acute harmful
      effect on fetal middle cerebral, placental and umbilical artery blood flow when
      UF rate of 2.1 +/- 0.04 L (6 < 8 mL/h/kg) during HD session, no significant
      statistical difference was observed when compared PI and RI before and after UF
      and also when we compared these data with reference value on normal pregnancy to
      the same gestational age. DISCUSSION: UF rate of 6 < 8 mL/h/kg during HD did not
      bring any acute harmful effect on fetal middle cerebral, placental, and umbilical
      blood flow and the UF rate of 1.4 6 0.4 L (< 6 mL/h/kg) / HD session that was
      done in all others HD during pregnancy was safe, without any chronic fetal
      deleterious effect. Obstetric Doppler ultrasonography is a simple and noninvasive
      method to fetal follow-up and can aid to determine safe UF rate in pregnant women
      during gestation.

PMID- 29227584
TI  - Npas4 deficiency and prenatal stress interact to affect social recognition in
      mice.
AB  - Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia
      have an expansive array of reported genetic and environmental contributing
      factors. However, none of these factors alone can account for a substantial
      proportion of cases of either disorder. Instead, many gene-by-environment
      interactions are responsible for neurodevelopmental disturbances that lead to
      these disorders. The current experiment used heterozygous knock-out mice to
      examine a potential interaction between 2 factors commonly linked to
      neurodevelopmental disorders and cognitive deficit: imbalanced
      excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure.
      Both of these factors have been linked to disrupt GABAergic signaling in the
      prefrontal cortex (PFC), a common feature of neurodevelopmental disorders. The
      neuronal PAS domain protein 4 (Npas4) gene is instrumental in regulation of the
      excitatory/inhibitory balance in the cortex and hippocampus in response to
      activation. Npas4 heterozygous and wild-type male and female mice were exposed to
      either PNS or standard gestation, then evaluated during adulthood in social and
      anxiety behavioral measures. The combination of PNS and Npas4 deficiency in male
      mice impaired social recognition. This behavioral deficit was associated with
      decreased parvalbumin and cFos protein expression in the infralimbic region of
      the PFC following social stimulation in Npas4 heterozygous males. In contrast,
      females displayed fewer behavioral effects and molecular changes in PFC in
      response to PNS and decreased Npas4.

PMID- 29227586
TI  - Identification of potential crucial genes associated with carcinogenesis of clear
      cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with
      high mortality. However, the molecular pathogenesis of ccRCC remains unclear and
      effective biomarkers for daily practice are still limited. Thus, we aimed to
      identify the potential crucial genes and pathways associated with carcinogenesis
      of ccRCC and further analyze the molecular mechanisms implicated in
      tumorigenesis. In the present study, expression profiles GSE 66270, GSE 53757,
      GSE 36895, and GSE 76351 were downloaded from GEO database, including 244 matched
      primary and adjacent normal tissues, furthermore, the level 3 RNAseq dataset
      (RNAseqV2 RSEM) of KIRC was also downloaded from The Cancer Genome Atlas (TCGA),
      which consist of 529 ccRCC tumors and 72 normal tissues. Then, differentially
      expressed genes (DEGs) and pathway enrichment were analyzed by using R software.
      A total of 129 up- and 123 down-regulated genes were identified, which were
      aberrantly expressed both in GEO and TCGA data. Second, Gene ontology (GO)
      analyses revealed that most of the DEGs were significantly enriched in integral
      component of membrane, extracellular exosome, plasma membrane, cell adhesion, and
      receptor binding. Signaling pathway analyses indicated that DEGs had common
      pathways in signal transduction, metabolism, and immune system. Third, hub genes
      were identified with protein-protein interaction (PPI) network, including PTPRC,
      TGFB1, EGF, MYC, ITGB2, CTSS, FN1, CCL5, KNG1, and CD86. Additionally, sub
      networks analyse was also performed by using MCODE plugin. In conclusion, the
      novel DEGs and pathways in ccRCC identified in this study may provide new insight
      into the underlying molecular mechanisms that facilitates RCC carcinogenesis.

PMID- 29227587
TI  - Corticosteroid Faceoff: Which is best for treating asthma and COPD exacerbations?

PMID- 29227588
TI  - Pushing EPI: Study shows optimal delivery time is after the second shock.

PMID- 29227589
TI  - Armed with History: Orange County, Calif., begins field implementation of EMS
      access to patient history via bidirectional information exchange.

PMID- 29227590
TI  - Value and Sustainability: Key metrics for mobile integrated healthcare and
      community paramedic programs.

PMID- 29227591
TI  - Expression of genes, encoding the enzymes of cysteine metabolism in human
      placenta in the first and third trimesters of uncomplicated pregnancy.
AB  - The cellular cysteine is highly regulated in a narrow range of concentrations due
      to its cyto- andneurtoxicity when it is overwhelmed or its deficiency for protein
      synthesis and other vital metabolic reactionswhen its amount is restricted. The
      regulation of cysteine content and its metabolic products, glutathione,
      taurineand inorganic sulfur compounds, is scarcely explored in human placenta
      though cysteine metabolism isclosely related to the maintenance of redox status
      and protection from free radical oxidation, elimination ofhomocysteine and
      detoxification. These processes are particularly important for placenta which
      meets substantialchanges of oxygen supply during its development, and is the last
      metabolically active organ betweenmother and fetus. The abundance of CDO , CSAD ,
      ADO , SUOX, GCLC and GCLM mRNAs was estimatedby RT -qPCR and compared with the
      computationally analyzed microarray gene expression data from GEO ,while the
      level of individual protein - by western-blot analysis, both in placental samples
      from first and thirdtrimesters of uncomplicated pregnancies. The abundance of CDO
      mRNA is significantly up-regulated at termcompared to the first trimester, the
      level of GCLM and GCLC mRNAs remains almost unchanged while theabundance of other
      mRNAs reduces to varying degrees. Overall, the changes of gene expression in
      third trimesterin comparison to the first one estimated by RT-qPCR and microarray
      coincide while the former dataare more informative for the limited group of
      genes. The data provide the basis for further research of thesegenes expression
      and phenotype of human placenta in health and disease

PMID- 29227592
TI  - Remodulating effect of doxorubicin on the state of iron-containing proteins, and
      redox characteristics of tumor with allowance for its sensitivity to cytostatic
      agents.
AB  - The study was aimed at determining the changes of metal-containing proteins in
      blood serum andtumor tissue of animals with parental and doxorubicin-resistant
      strains of Walker-256 carcinosarcoma beforeand after the cytostatic
      administration. It has been shown that upon doxorubicin action the levels of
      total ironand transferrin in the tissues from the both groups of animals
      decreased while that of ferritine simultaneouslyincreased with more pronounced
      pattern in the group of animals with resistant tumor strain. It has beenshown
      that upon the action of doxorubicin in tumor tissue of animals with different
      sensitivity to the cytostaticthere could be observed oppositely directed changes
      in the redox state of these cells that in turn determinedthe content of " free
      iron" complexes, RO S generation and concentration of active forms of matrix
      metaloproteinase-2 and matrix metaloproteinase-9, namely, the increase of these
      indexes in animals with parental strainand their decrease in animals with the
      resistant one. So, our study has demonstrated the remodulating effectof
      doxorubicin on the state of metal-containing proteins and redox characteristics
      of tumor dependent on itssensitivity to cytostatic, at the levels of the tumor
      and an organism. These data may serve as a criterion forthe development of
      programs for the correction of malfunction of iron metabolism aimed at elevating
      tumorsensitivity to cytostatic agents.

PMID- 29227593
TI  - Effect of beta-amyloid peptide 42 on the dynamics of expression and formation of
      Abeta40, IL -1beta, TNF alpha, IL -6, IL -10 by peripheral blood mononuclear
      cells in vitro and its correction by curcumin.
AB  - The toxic effect of Abeta-oligomers accompanies chronic inflammation, with
      cytokines as main mediators.Therefore, the cytokine link of inflammation becomes
      a new target on the way to restrain amyloidosis. The aimof the study was the
      effect of aggregated Abeta42 on the dynamics of expression and formation of
      endogenous Abeta40and cytokines (IL-1beta, TNFalpha, IL-6, IL-10) by peripheral
      blood mononuclear cells in vitro and its correctionby curcumin. A suspension of
      mononuclear cells isolated ex tempore using ficoll-urografin gradient fromvenous
      blood samples of healthy volunteers were used to study the effects of Abeta42 (15
      nM), curcumin (54 pM),and their combined action (at similar concentrations) in
      time dynamics: 0, 1, 3, 6 and 24 h incubation at37  degrees C. Polymerase chain
      reaction with appropriate primers was used to determine the relative expressionof
      mRNA for AbetaPP, TNFalpha, IL-1beta, IL-6, IL-10 and enzyme-linked immunosorbent
      assay - to determine thecontent of Abeta40 and cytokines in mononuclear
      suspension during all periods of incubation. The individualdynamics AbetaPP and
      cytokine expression was shown under the action of the Abeta42, which had
      influence on thecontent of Abeta40, TNFalpha, IL-1beta, IL-6 and IL-10 in
      mononuclear suspension. Curcumin displayed the inhibitoryeffect on gene
      expression of AbetaPP, TNFalpha and IL6, which resulted in the decrease of the
      level of these twocytokines and Abeta40. Thus, the dynamics of anti-inflammatory
      effect of curcumin in vitro for transcriptionaland translational levels of
      cytokine's formation by mononuclear cells was shown in the work. Direct
      inhibitoryeffect of curcumin on the concentration of endogenous Abeta40 during
      the 24 h incubation in conditions of toxicaction of Abeta42 aggregates was
      established.

PMID- 29227594
TI  - Transcriptional regulation of NOX genes express ion in human breast
      adenocarcinoma MCF-7 cells is modulated by adaptor protein Ruk/CIN 85.
AB  - NADPH oxidases are key components of redox-dependent signaling networks involved
      in the controlof cancer cell proliferation, survival and invasion. The data have
      been accumulated that demonstrate specificexpression patterns and levels of NADPH
      oxidase homologues (NOXs) and accessory genes in human cancercell lines and
      primary tumors as well as modulation of these parameters by extracellular cues.
      Our previousstudies revealed that ROS production by human colorectal
      adenocarcinoma HT-29 cells is positively correlatedwith adaptor protein Ruk/CIN85
      expression while increased levels of Ruk/CIN85 in weakly invasive humanbreast
      adenocarcinoma MC F-7 cells contribute to their malignant phenotype through the
      constitutiveactivation of Src/Akt pathway. In this study, to investigate whether
      overexpression of Ruk/CIN85 in MC F-7cells can influence transcriptional
      regulation of NOXs genes, the subclones of MCF-7 cells with differentlevels of
      Ruk/CIN85 were screened for NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 as well
      as forregulatory subunit p22Phox mRNA contents by quantitative RT-PCR (qPCR).
      Systemic multidirectional changesin mRNA levels for NOX1, NOX2, NOX5, DUOX2 and
      p22Phox were revealed in Ruk/CIN85 overexpressingcells in comparison to control
      WT cells. Knocking down of Ruk/CIN85 using technology of RNA-interferenceresulted
      in the reversion of these changes. Further studies are necessary to elucidate, by
      which molecularmechanisms Ruk/CIN85 could affect transcriptional regulation of
      NOXs genes.

PMID- 29227595
TI  - [Analysis of inventive activity of the department of vitamin and coenzyme
      biochemistry of Palladin Institute of Biochemistry NAS of Ukraine in the period
      of 1980-2015].

PMID- 29227596
TI  - The inhibitory influence of calix[4]Arene of C-90 on the activity of Ca2+,Mg2+
      ATPases in plasma membrane and sarcoplasmic reticulum in myometrium cells.
AB  - Our study on the plasma membrane vesicles and myometrium cells treated with 0.1%
      digitonin showedthat inhibitory effect of calix[4]arene C-90 (5,11,17,23
      tetra(trifluoro)methyl(phenylsulphonylimino)-methylamino-25,26,27,28-tetrapropoxy
      calix[4]arene) on the plasma membrane Ca2+,Mg2+-ATPase was more significantthan
      on the Ca2+,Mg2+-ATPase in sarcoplasmic reticulum (the inhibition coefficient
      I0.5 values were20.2 +/- 0.5 MUM and 57.0 +/- 1.4 MUM for the plasma membrane
      Ca2+,Mg2+-ATPase and Ca2+,Mg2+-ATPase insarcoplasmic reticulum, respectively (n =
      5)). Inhibition kinetics of calix[4]arene C-90 effect on the Ca2+,Mg2+-ATPase
      activities in plasma membrane and sarcoplasmic reticulum were studied. This
      substance inhibitedboth pumps as complete noncompetitive inhibitor. Calix[4]arene
      C-90 caused the increase of intracellularCa2+ concentration and decrease of
      hydrodynamic diameter in smooth muscle cells similar to the action ofuterotonic
      drug oxytocin.

PMID- 29227597
TI  - Effect of fibrin degradation products on fibrinolytic process.
AB  - Fibrin clot lysis by plasminogen/plasmin system results in fibrin degradation
      products formation withsubsequent release into bloodstream. The fragments contain
      specific binding sites for fibrinolytic system componentsand can interact with
      them. In this study, we investigated the way in which fibrin fragments
      effectfibrinolytic process. We have shown that high molecular weight products of
      fibrin degradation and fibrin fragmentsof DDE-complex and DD, but not end product
      E3, stimulate plasmin formation. Additionally, componentsof DDE-complex mixture
      of fragments E1 and E2 have potentiation ability. The intermediate fibrin
      fragmentshmFDPs and DDE attenuate clot lysis by plasmin and hmFDPs protect
      plasmin from alpha2-antiplasmininhibition but under further fragmentation to
      endpoint fibrin fragments loose this ability. The plasma inhibitorsreduce
      fibrinolytic system activity generated by the degradation products. Thus, fibrin
      fragments formedduring the clot lysis can bind and move out fibrinolytic system
      components from clot volume and in this wayresult in clot resistance to
      hydrolysis.

PMID- 29227598
TI  - Event Medicine: Pearls and pitfalls of managing mass gatherings.

PMID- 29227599
TI  - Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene
      expressions in U87 glioma cells.
AB  - We have studied hypoxic regulation of the expression of genes encoded GADD
      (growth arrest and DNAdamage) family proteins in U87 glioma cells in relation to
      inhibition of IRE1 (inositol requiring enzyme-1),which controls cell
      proliferation and tumor growth as a central mediator of endoplasmic reticulum
      stress.We have shown that hypoxia up-regulates the expression of GADD34, GADD45A,
      GADD45B, and GADD153genes, which are related to cell proliferation and apoptosis,
      in control (transfected by empty vector) gliomacells in gene specific manner. At
      the same time, the expression level of EIF2AK 1 (eukaryotic translation
      initiationfactor 2-alpha kinase 1) and AI FM1 (apoptosis inducing factor,
      mitochondria associated 1) genes inthese cells is down-regulated upon hypoxic
      condition. It was also shown that inhibition of IRE1 signaling enzymefunction in
      U87 glioma cells enhances the effect of hypoxia on these genes expression, except
      EIF2AK 1and AI FM1 genes. Furthermore, the expression of all studied genes in
      IRE1 knockdown cells is significantlydecreased upon normoxic condition, except
      GADD45B gene, which expression level is strongly up-regulated.Therefore, the
      expression level of genes encoding GADD34, GADD45A, GADD45B, GADD153, EIF2AK 1,
      andAI FM1 is affected by hypoxia and by inhibition of IRE1-mediated endoplasmic
      reticulum stress signaling ingene specific manner and correlates with suppression
      of glioma cell proliferation upon inhibition of the IRE1enzyme function.

PMID- 29227601
TI  - Clean it Up: Strategies for keeping you and your patients infection-free.

PMID- 29227600
TI  - Cardiovascular disease among patients with type 2 diabetes: Role of Homocysteine
      as an inflammatory marker.
AB  - It is known that inflammation has a role in the pathogenesis of cardiovascular
      diseases; measurementof inflammatory markers improves the risk prediction of
      cardiovascular diseases. Hyperhomocysteinemia hasbeen correlated with the
      occurrence of blood clots, heart attacks and strokes; though it is unclear
      whetherhyperhomocysteinemia is an independent risk factor for these conditions.
      In the present study, we aimed toevaluate the role of homocysteine in type 2
      diabetes patients with cardiovascular disease in a populationof Madhya Pradesh
      India. Total 100 type 2 diabetes patients were included in the study, of these 50
      hadangiographically proven cardiovascular disease and 50 had no evidence of it.
      High sensitivity C-reactiveprotein, fibrinogen, and lipoprotein (a) were measured
      in serum. Homocysteine, blood glucose in plasma,erythrocyte sedimentation rate,
      glycated haemoglobin were measured in whole blood. A albumin excretionrate,
      creatinine clearance rate were measured in the urine sample for renal function.
      It was shown that,levels of homocysteine and other inflammatory markers were
      elevated significantly in the group II (n = 50).A correlation between
      hyperhomocysteinemia and inflammatory markers in patients with impaired
      renalfunction was observed. It was concluded that impairment of renal function is
      a key factor that affectshomocysteine level.

PMID- 29227602
TI  - Effects of the combined arginase and canavanine treatment on leukemic cells in
      vitro and in vivo.
AB  - It was previously demonstrated in in vitro experiments that canavanine (Cav), a
      natural toxic arginineanalogue of plant origin, is a promising candidate for
      augmenting the antineoplastic effects of argininestarvation. We demonstrated
      herein that recombinant human arginase, an arginine degrading enzyme,abrogated
      growth and significantly increased Cav cytotoxicity toward cultured L1210 murine
      leukemic cells.Cav co-treatment further reduced cells viability in a time
      dependent manner and significantly promotedapoptosis induction. In the pilot
      study we also evaluated for the first time the potential toxicity of the
      combinedarginine deprivation and Cav treatment in healthy mice. Administration of
      Cav alone or in combinationwith pegylated cobalt-containing human arginase (Co
      hARG) did not evoke any apparent toxic effects inthese animals, with no
      significant behavioural and survival changes after several weeks of the
      treatment.The therapeutic effects of the combination of Co-hARG and Cav were
      provisionally evaluated on the highlyaggressive murine L1210 leukemia, which is
      semi-sensitive to arginine deprivation as a monotreatment.Combination of two
      drugs did not result in significant prolongation of the survival of leukemia
      bearing mice.Thus, we have shown that the proposed combinational treatment is
      rather non-toxic for the animals. It hasto be further evaluated in animal studies
      with alternative tumor models and/or drug doses and treatmentmodalities.

PMID- 29227605
TI  - Level of overall hemostasis potential in donor and patient plasma in pathology.
AB  - Coagulation potential (CP), overall hemostasis potential (OHP) and fibrinolysis
      potential (FP) inplasma of donors and patients with myocardial infarction (MI),
      stroke (St) and hip joint diseases (HJD) havebeen investigated using M.
      Blomback's global hemostasis assay. Plasma samples of the patients were
      analyzedwith APTT reagent in the presence or absence of t-PA. It was found that
      the ratio of values of SP, OHPand FP in plasma of patients to those of donors
      plasma were 78, 60 and 123% at MI; 157, 155 and 162% atSt; 128, 131 and 124% at
      HJD. CP to FP ratio that indicated balance between coagulation and
      fibrinolyticsystems activities were 4.13, 2.5, 4.0 and 4.26 in plasma of donors
      and MI, St and HJD patients, respectively.These results are evidence of increased
      fibrinolytic activity in plasma of MI patients. Lag-periods of plasmaclotting of
      MI, St and HJD patients were prolonged by 2.3, 7.2 and 1.5-fold, respectively.
      Pearson's correlationanalysis between parameters, obtained in vitro studies using
      global hemostasis assay, and concentrationsof the molecular markers (soluble
      fibrin and D-dimer), which formed in vivo in plasma of MI, St and HJDpatients,
      did not reveal any relationship between them.

PMID- 29227606
TI  - Peculiarities of the free radical processes in rat liver mitochondria under toxic
      hepatitis on the background of alimentary protein deficiency.
AB  - The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide
      generation, the levelof oxidative modification of mitochondrial proteins in the
      liver of rats with toxic hepatitis was investigated onthe background of
      alimentary protein deficiency. We did not find significant increases of the
      intensity of freeradical processes in liver mitochondria of rats maintained on
      the protein-deficient ration. The most significantintensification of free radical
      processes in liver mitochondria is observed under the conditions of toxic
      hepatitis,induced on the background of alimentary protein deprivation. Under
      these conditions the aggravation ofall studied forms of reactive oxygen species
      generation was observed in liver mitochondria. The generationrates were increased
      as follows: O2 - by 1.7 times, N2O2 - by 1.5 times, *ON - practically double on
      the backgroundof accumulation of oxidized mitochondria-derived proteins. The
      established changes in thiol groups'redox status of respiratory chain proteins
      insoluble in 0.05 M sodium-phosphate buffer (pH 11.5), and changesof their
      carbonyl derivatives content may be considered as one of the regulatory factors
      of mitochondrialenergy-generating function.

PMID- 29227607
TI  - Assessing O2 Saturation: The how, what and why of pulse oximetry.

PMID- 29227608
TI  - Physical-chemical properties and the reactivity of pyridoxine and pyrrolidone
      carboxylate and their protolytic forms.
AB  - Preparation Methadoxine is equimolar salt, which cationic component (pyridoxine)
      is 3-oxypyridinederivative, possessing B6-vitamine like activity, while anionic
      component is the cyclic lactame of glutamicacid. Since biopharmaceutical and
      pharmacological properties of this drug depend on biochemical transformationits
      components, of the aim of this work was to determine the structure of possible
      ionized pyridoxineand pyrrolidone carboxylate forms and their reaction ability in
      biochemical processes. Physical-chemicalproperties of compounds (pKa, logP, logD,
      proton donor/acceptor quantity, solubility (g/l)) were calculatedwith ACD/pKaDB
      program or obtained from Pub-Med physical/chemical properties database. UV
      spectra ofcompounds were obtained after dissolution in different pH solutions
      (1.0, 4.5 and 6.8). It was found that at differentpH values one can observe
      changes of the absorption spectra due to the presence of prevailing amountof the
      protonated form. An analysis of both pKa, logP and logD indicators and reactive
      functional groups ofMethadoxine components has revealed that they can be
      protonated in different regions of gastro-intestinaltract, that influences their
      solubility in hydrophilic and lypophilic media. Pharmacological properties of
      pyridoxineand pyrrolidone carboxylate themselves are performed after their
      preliminary biotransformation toactive metabolites. Only ionic interaction
      between Methadoxine components in the substance composition canappear, that
      provides its pharmaceutical stability and ensures its activity only in the
      organism conditions.

PMID- 29227609
TI  - The effect of chlorpyrifos upon ATPase activity of sarcoplasmic reticulum and
      biomechanics of skeleta l muscle contraction.
AB  - We investigated the effect of chlorpyrifos, an organophosphate insecticide, on
      Ca2+,Mg2+-ATPaseactivity of sarcoplasmic reticulum and on contraction dynamics
      (force and length changes) of Rana temporariam. tibialis anterior muscle fiber
      bundles. All of the used concentrations of chlorpyrifos (10-6 to 10-5 M)
      causeddecrease of Ca2+,Mg2+-ATPase activity. The inhibition of Ca2+,Mg2+-ATPase
      activity by chlorpyriphos inconcentrations of 10-6 M to 7.5.10-6 M is due to
      permeation of sarcoplasmic reticulum rather than due todirect enzyme inhibition
      by organophosphate insecticides. The inhibitory properties of the compound
      werehigher at increased concentration and exposure timeframes. Chlorpyrifos in
      concentration range of 10-6to 7.5.10-6 M causes changes in muscle fiber response
      force that were more pronounced than changes incontractile length. We
      demonstrated inhibition of Ca2+,Mg2+-ATPase activity caused by
      noncholinergiceffects of chlorpyriphos. It is possible to conclude that influence
      of organophosphate insecticides happensnot only in the neuromuscular transmission
      but also on the level of subcellular structures.

PMID- 29227610
TI  - Gene expression of H+-pumps in plasma and vacuolar membranes of corn root cells
      under the effect of sodium ions and bioactive preparations.
AB  - Four isoforms of H+-ATPase of plasma membrane: MHA1, MHA2, MHA3, MHA4 are
      expressed inthe corn seedling roots with prevalence of genes MHA3 i MHA4. The
      exposure of seedlings in the presenceof 0.1 M NaCl activated the expression of
      MHA4 gene isoform, that demonstrates its important role in theprocesses of
      adaptation to salinization conditions. In vacuolar membrane, where potential is
      created bytwo N+-pumps, sodium ions activated gene expression of only N+-ATRase
      of V-type, taking no effect on theexpression of N+-pyrophosphatase. The seeds
      pretreatment by synthetic preparations Methyure and Ivine didnot affect gene
      expression of N+-pumps. Thus we can suppose that the ability of the above
      preparations toactivate functioning of N+-pumps in the presence of sodium ions is
      realized at the post-tranlation level.

PMID- 29227612
TI  - Dead Heat: Treating exertional heat stroke is a race against time and
      temperature.

PMID- 29227611
TI  - Cytochrome P450 2E1 participation in the pathogenesis of experimental metabolic
      syndrome in guinea pigs.
AB  - In this work the experimental metabolic syndrome on the basis of protamine
      sulfate modeling inguinea pigs was reproduced and pathological processes in the
      liver of experimental animals were studied.We determined the level of free
      radicals and markers of liver damage in the blood of experimental animals.We
      investigated the liver glycogen content and K+,Na+-ATPase activity in the liver
      of experimental animalsas well as measured the cytochrome P450 2E1 (CY P2E1)
      expression - one of the main factors of oxidativestress. Evidence of development
      of hepatotoxic processes, increasing of the CY P2E1 level as well as of thefree
      radical level in the animals with metabolic syndrome were found. Using of CY P2E1
      inhibitors had shownthat the free radical level in the blood of experimental
      animals depended on the level of the enzyme expressionand activity. The obtained
      results suggest that the changes in the CY P2E1 expression play an importantrole
      in the development of hepatotoxic processes upon experimental metabolic syndrome.
      It was assumed thatpharmacological correction of the enzyme expression may be an
      important mechanism for the influence onthe metabolic syndrome clinical course.

PMID- 29227614
TI  - Hands On: Product Reviews From Street Crews.

PMID- 29227613
TI  - [Inventive activity of the Department of Protein Structure and Function of the
      Palladin Institute of Biochemistry of NAS of Ukraine. Part I. Development of the
      diagnostic methods for detection of hemostasis disorders and characterization of
      certain blood coagulation factors].

PMID- 29227615
TI  - Clinical Errors: Identifying and learning from mistakes in patient care.

PMID- 29227616
TI  - Last Word: The Ups and Downs of EMS.

PMID- 29227617
TI  - Electrochemical Interphases for High-Energy Storage Using Reactive Metal Anodes.
AB  - Stable electrochemical interphases play a critical role in regulating transport
      of mass and charge in all electrochemical energy storage (EES) systems. In state
      of-the-art rechargeable lithium ion batteries, they are rarely formed by design
      but instead spontaneously emerge from electrochemical degradation of electrolyte
      and electrode components. High-energy secondary batteries that utilize reactive
      metal anodes (e.g., Li, Na, Si, Sn, Al) to store large amounts of charge by
      alloying and/or electrodeposition reactions introduce fundamental challenges that
      require rational design in order to stabilize the interphases. Chemical
      instability of the electrodes in contact with electrolytes, morphological
      instability of the metal-electrolyte interface upon plating and stripping, and
      hydrodynamic-instability-induced electroconvection of the electrolyte at high
      currents are all known to cause metal electrode-electrolyte interfaces to
      continuously evolve in morphology, uniformity, and composition. Additionally,
      metal anodes undergo large changes in volume during lithiation and delithiation,
      which means that even in the rare cases where spontaneously formed solid
      electrode-electrolyte interphases (SEIs) are in thermodynamic equilibrium with
      the electrode, the SEI is under dynamic strain, which inevitably leads to
      cracking and/or rupture during extended battery cycling. There is an urgent need
      for interphases that are able to overcome each of these sources of instability
      with minimal losses of electrolyte and electrode components. Complementary
      chemical synthesis strategies are likewise urgently needed to create self-limited
      and mechanically durable SEIs that are able to flex and shrink to accommodate
      volume change. These needs are acute for practically relevant cells that cannot
      utilize large excesses of anode and electrolyte as employed in proof-of-concept
      type experiments reported in the scientific literature. This disconnect between
      practical needs and research practices makes it difficult to translate promising
      literature results, underscoring the importance of research designed to reveal
      principles for good interphase design. This Account considers the fundamental
      processes involved in interphase formation, stability, and failure and on that
      basis identifies design principles, synthesis procedures, and characterization
      methods for enabling stable metal anode-electrolyte interfaces for EES. We first
      review results from experimental, continuum theoretical, and computational
      analyses of interfacial transport to identify fundamental connections between the
      composition of the SEI at metal-electrolyte interfaces and stability. Design
      principles and tools for creating stable artificial solid-electrolyte interphases
      (ASEIs) based on polymers, ionic liquids, ceramics, nanoparticles, salts, and
      their combinations are subsequently discussed. Interphases composed of a second
      electrochemically active material that stores charge by different processes from
      the underlying metal electrode emerge as particularly attractive routes toward so
      called hybrid electrodes that enable facile scale-up of ASEI designs for
      commercially relevant EES.

PMID- 29227618
TI  - Tackling the Challenges of Dynamic Experiments Using Liquid-Cell Transmission
      Electron Microscopy.
AB  - Revolutions in science and engineering frequently result from the development,
      and wide adoption, of a new, powerful characterization or imaging technique.
      Beginning with the first glass lenses and telescopes in astronomy, to the
      development of visual-light microscopy, staining techniques, confocal microscopy,
      and fluorescence super-resolution microscopy in biology, and most recently
      aberration-corrected, cryogenic, and ultrafast (4D) electron microscopy, X-ray
      microscopy, and scanning probe microscopy in nanoscience. Through these
      developments, our perception and understanding of the physical nature of matter
      at length-scales beyond ordinary perception have been fundamentally transformed.
      Despite this progression in microscopy, techniques for observing nanoscale
      chemical processes and solvated/hydrated systems are limited, as the necessary
      spatial and temporal resolution presents significant technical challenges.
      However, the standard reliance on indirect or bulk phase characterization of
      nanoscale samples in liquids is undergoing a shift in recent times with the
      realization ( Williamson et al. Nat. Mater . 2003 , 2 , 532 - 536 ) of liquid
      cell (scanning) transmission electron microscopy, LC(S)TEM, where picoliters of
      solution are hermetically sealed between electron-transparent "windows," which
      can be directly imaged or videoed at the nanoscale using conventional
      transmission electron microscopes. This Account seeks to open a discussion on the
      topic of standardizing strategies for conducting imaging experiments with a view
      to characterizing dynamics and motion of nanoscale materials. This is a challenge
      that could be described by critics and proponents alike, as analogous to doing
      chemistry in a lightning storm; where the nature of the solution, the
      nanomaterial, and the dynamic behaviors are all potentially subject to
      artifactual influence by the very act of our observation.

PMID- 29227620
TI  - Nano Ag/ZnO-Incorporated Hydroxyapatite Composite Coatings: Highly Effective
      Infection Prevention and Excellent Osteointegration.
AB  - Interfacial characteristics play an important role in infection prevention and
      osteointegration of artificial bone implants. In this work, both Ag nanoparticles
      (AgNPs) and ZnO NPs are incorporated into hydroxyapatite (HA) nanopowders and
      deposited onto Ti6Al4V (Ti6) implants by laser cladding. The composite coatings
      possess a hierarchical surface structure with homogeneous distributions of Ag and
      ZnO. The Ag and ZnO NPs that are immobilized by laser cladding ensure long-term
      and gradual release of Ag and Zn ions at low cumulative concentrations of 36.2
      and 56.4 MUg/L after immersion for 21 days. A large concentration of Ag released
      initially increases the cytotoxicity but the large initial ZnO content enhances
      the cell viability and osteogenetic ability. The nano Ag/ZnO-embedded HA coating
      (Ag/ZnO/HA = 7:3:90 wt %, namely Ag7ZnO3HA) exhibits optimal antibacterial
      efficacy and osteogenetic capability, as exemplified by the broad spectrum
      antibacterial efficacy of 96.5 and 85.8% against Escherichia coli (E. coli) and
      Staphylococcus aureus (S. aureus), respectively, together with enhanced
      osteoinductivity with higher alkaline phosphatase (ALP) activity of 134.60 U/g
      protein compared to 70.79 U/g protein for the untreated implants after culturing
      for 7 days. The rabbit femoral implant model further confirms that the optimized
      composite coating accelerates the formation of new bone tissues indicating 87.15%
      of the newly formed bone area and osteointegration showing 83.75% of the bone
      implant contact area even in the presence of injected S. aureus. The laser
      cladded Ag7ZnO3HA composite coatings are promising metallic implants with
      excellent intrinsic antibacterial activity and osteointegration ability.

PMID- 29227619
TI  - Small Molecule Chelators Reveal That Iron Starvation Inhibits Late Stages of
      Bacterial Cytokinesis.
AB  - Bacterial cell division requires identification of the division site, assembly of
      the division machinery, and constriction of the cell envelope. These processes
      are regulated in response to several cellular and environmental signals. Here, we
      use small molecule iron chelators to characterize the surprising connections
      between bacterial iron homeostasis and cell division. We demonstrate that iron
      starvation downregulates the transcription of genes encoding proteins involved in
      cell division, reduces protein biosynthesis, and prevents correct positioning of
      the division machinery at the division site. These combined events arrest the
      constriction of the cell during late stages of cytokinesis in a manner distinct
      from known mechanisms of inhibiting cell division. Overexpression of genes
      encoding cell division proteins or iron transporters partially suppresses the
      biological activity of iron chelators and restores growth and division. We
      propose a model demonstrating the effect of iron availability on the regulatory
      mechanisms coordinating division in response to the nutritional state of the
      cell.

PMID- 29227621
TI  - Facet-Dependent Electrical, Photocatalytic, and Optical Properties of
      Semiconductor Crystals and Their Implications for Applications.
AB  - Recent studies on the electrical conductivity and photocatalytic activity
      properties of semiconductor nanocrystals such as Cu2O, Ag2O, TiO2, PbS, and
      Ag3PO4 exposing well-defined surfaces have revealed strong facet effects. For
      example, the electrical conductivity of Cu2O crystals can vary from highly
      conductive to nonconductive, and they can be highly photocatalytically active or
      inactive depending on the exposed faces. The crystal surfaces can even tune their
      light absorption wavelengths. Our understanding is that the emergence of these
      unusual phenomena can be explained in terms of the presence of an ultrathin
      surface layer having different band structures and degrees of band bending for
      different surfaces, which affects charge transport and photons into and out of
      the crystals. This review uses primarily results from our research on this
      frontier area of semiconductor properties to illustrate the existence of
      semiconductor facet effects. A simple adjustment to normal semiconductor band
      diagram allows good understanding of the observed phenomena. Recognizing that
      facet-dependent behaviors are intrinsic semiconductor properties, we should pay
      attention to their influence in the explanation of the measured photocatalytic
      properties, and consider ways to enhance photocatalytic efficiency or design
      electrical components utilizing the facet effects. There should be many
      opportunities to advance applications of semiconductor nanocrystals and
      nanostructures with continued research on the facet-dependent properties of
      various semiconductor materials.

PMID- 29227622
TI  - N-Doped Graphene Quantum Dots-Decorated V2O5 Nanosheet for Fluorescence Turn Off
      On Detection of Cysteine.
AB  - The development of a fast-response sensing technique for detection of cysteine
      can provide an analytical platform for prescreening of disease. Herein, we have
      developed a fluorescence turn off-on fluorescence sensing platform by combining
      nitrogen-doped graphene quantum dots (N-GQDs) with V2O5 nanosheets for the
      sensitive and selective detection of cysteine in human serum samples. V2O5
      nanosheets with 2-4 layers are successfully synthesized via a simple and scalable
      liquid exfoliation method and then deposited with 2-8 nm of N-GQDs as the
      fluorescence turn off-on nanoprobe for effective detection of cysteine in human
      serum samples. The V2O5 nanosheets serve as both fluorescence quencher and
      cysteine recognizer in the sensing platform. The fluorescence intensity of N-GQDs
      with quantum yield of 0.34 can be quenched after attachment onto V2O5 nanosheets.
      The addition of cysteine triggers the reduction of V2O5 to V4+ as well as the
      release of N-GQDs within 4 min, resulting in the recovery of fluorescence
      intensity for the turn off-on detection of cysteine. The sensing platform
      exhibits a two-stage linear response to cysteine in the concentration range of
      0.1-15 and 15-125 MUM at pH 6.5, and the limit of detection is 50 nM. The
      fluorescence response of N-GQD@V2O5 exhibits high selectivity toward cysteine
      over other 22 electrolytes and biomolecules. Moreover, this promising platform is
      successfully applied in detection of cysteine in human serum samples with
      excellent recovery of (95 +/- 3.8) - (108 +/- 2.4)%. These results clearly
      demonstrate a newly developed redox reaction-based nanosensing platform using N
      GQD@V2O5 nanocomposites as the sensing probe for cysteine-associated disease
      monitoring and diagnosis in biomedical applications, which can open an avenue for
      the development of high performance and robust sensing probes to detect organic
      metabolites.

PMID- 29227623
TI  - Virtual Out-of-Plane Piezoelectric Response in MoS2 Layers Controlled by
      Ferroelectric Polarization.
AB  - The MoS2 carrier distribution can be controlled with the use of a dielectric
      environment substrate. Ferroelectric thin films are used to investigate the
      electrical responses at the MoS2 layer. The MoS2/(111)-PbTiO3 vertical
      heterostructure is investigated, and the electrical responses, including
      piezoelectricity, are obtained using piezoresponse force microscopy. The
      piezoelectric response modifications obtained at the MoS2 layer on the
      ferroelectric thin films are a result of the depolarizing effect. In particular,
      the piezoelectricity enhancement is observed at the 19-layer MoS2 because of an
      induced dipole effect. By considering the polarization effects of ferroelectric
      thin films, the electrical responses at the MoS2 layers can be controlled, and
      the interfacial carrier distribution at the interface results in different
      electrical performances at the MoS2.

PMID- 29227624
TI  - Deliberately Designed Atomic-Level Silver-Containing Interface Results in
      Improved Rate Capability and Utilization of Silver Hollandite for Lithium-Ion
      Storage.
AB  - alpha-MnO2-structured materials are generally classified as semiconductors; thus,
      we present a strategy to increase electrochemical utilization through the design
      of a conductive material interface. Surface treatment of silver hollandite
      (AgxMn8O16) with Ag+ (Ag2O) provides significant benefits to the resultant
      electrochemistry, including a decreased charge-transfer resistance and a 2-fold
      increase in deliverable energy density at a high rate. The improved function of
      this designed interface relative to conventional electrode fabrication strategies
      is highlighted.

PMID- 29227626
TI  - Cellular Bioparticulates with Therapeutics for Cancer Immunotherapy.
AB  - Cancer immunotherapy has received considerable attention because of a variety of
      exciting clinical outcomes in recent years. At the interface of cancer
      immunotherapy and bioengineering, there are many opportunities to further improve
      the treatment efficacy or address current challenges in immunotherapy. Cellular
      bioparticulates as promising carriers of immunomodulators have attracted much
      attention due to their inherent biocompatibility and unique biological
      properties. This Topical Review highlights recently reported studies utilizing
      bioparticulates for cancer immunotherapy, including engineered red blood cells
      (RBC) and RBC membrane coated particles, engineered T-cells, engineered
      platelets, and engineered microbes.

PMID- 29227625
TI  - Genetic Reduction or Negative Modulation of mGlu7 Does Not Impact Anxiety and
      Fear Learning Phenotypes in a Mouse Model of MECP2 Duplication Syndrome.
AB  - Rett syndrome and MECP2 Duplication syndrome are neurodevelopmental disorders
      attributed to loss-of-function mutations in, or duplication of, the gene encoding
      methyl-CpG-binding protein 2 (MeCP2), respectively. We recently reported
      decreased expression and function of the metabotropic glutamate receptor 7
      (mGlu7) in a mouse model of Rett syndrome. Positive allosteric modulation of
      mGlu7 activity was sufficient to improve several disease phenotypes including
      cognition. Here, we tested the hypothesis that mGlu7 expression would be
      reciprocally regulated in a mouse model of MECP2 Duplication syndrome, such that
      negative modulation of mGlu7 activity would exert therapeutic benefit. To the
      contrary, we report that mGlu7 is not functionally increased in mice
      overexpressing MeCP2 and that neither genetic nor pharmacological reduction of
      mGlu7 activity impacts phenotypes that are antiparallel to those observed in Rett
      syndrome model mice. These data expand our understanding of how mGlu7 expression
      and function is affected by changes in MeCP2 dosage and have important
      implications for the therapeutic development of mGlu7 modulators.

PMID- 29227627
TI  - Correction to Exploiting Particle Mutual Interactions to Enable Challenging
      Dielectrophoretic Processes.

PMID- 29227628
TI  - Metabolic Measurements of Nonpermeating Compounds in Live Cells Using
      Hyperpolarized NMR.
AB  - Hyperpolarization by dissolution dynamic nuclear polarization (D-DNP) has emerged
      as a technique for enhancing NMR signals by several orders of magnitude, thereby
      facilitating the characterization of metabolic pathways both in vivo and in
      vitro. Following the introduction of an externally hyperpolarized compound, real
      time NMR enables the measurement of metabolic flux in the corresponding pathway.
      Spin relaxation however limits the maximum experimental time and prevents the use
      of this method with compounds exhibiting slow membrane transport rates. Here, we
      demonstrate that on-line electroporation can serve as a method for membrane
      permeabilization for use with D-DNP in cell cultures. An electroporation
      apparatus hyphenated with stopped-flow sample injection permits the introduction
      of the hyperpolarized metabolite within 3 s after the electrical pulse. In yeast
      cells that do not readily take up pyruvate, the addition of the electroporation
      pulse to the D-DNP experiment increases the signals of the downstream metabolic
      products CO2 and HCO3-, which otherwise are near the detection limit, by 8.2- and
      8.6-fold. Modeling of the time dependence of these signals then permits the
      determination of the respective kinetic rate constants. The observed conversion
      rate from pyruvate to CO2 normalized for cell density was found to increase by a
      factor of 12 due to the alleviation of the membrane transport limitation. The use
      of electroporation therefore extends the applicability of D-DNP to in vitro
      studies with a wider range of metabolites and at the same time reduces the
      influence of membrane transport on the observed conversion rates.

PMID- 29227629
TI  - Neutral and Cationic Zirconium Complexes Bearing Multidentate Aminophenolato
      Ligands for Hydrophosphination Reactions of Alkenes and Heterocumulenes.
AB  - Zirconium complexes supported by multidentate aminophenolato ligands were
      synthesized and characterized. The catalytic activities of neutral zirconium
      complexes and their cationic derivatives in the hydrophosphination of alkenes as
      well as heterocumulenes have been investigated and compared. Neutral complex 1
      bearing a multidentate amino mono(phenolato) ligand exhibited high activity in
      hydrophosphination of simple alkenes, and anti-Markovnikov products were obtained
      in 37-94% yields at room temperature. Cationic species generated in situ from
      complex 3 stabilized by a bis(phenolato) ligand were found to be more active for
      hydrophosphination of heterocumulenes, i.e., carbodiimides and isocyanates, and
      gave phosphaguanidines and phosphaureas in 67-93% yields. The Lewis acidity and
      coordination space of metal centers are modified through changes in the ligand
      structure, which is found to significantly influence catalytic activity. These
      complexes are among the most active group 4 metal-based catalysts for
      hydrophosphination reactions.

PMID- 29227630
TI  - Correction to Structural Effects of Single Mutations in a Filamentous Viral
      Capsid Across Multiple Length Scales.

PMID- 29227631
TI  - Helium Ion Microscopy for Imaging and Quantifying Porosity at the Nanoscale.
AB  - Nanoporous materials are key components in a vast number of applications from
      energy to drug delivery and to agriculture. However, the number of ways to
      analytically quantify the salient features of these materials, for example:
      surface structure, pore shape, and size, remain limited. The most common approach
      is gas absorption, where volumetric gas absorption and desorption are measured.
      This technique has some fundamental drawbacks such as low sample throughput and a
      lack of direct surface visualization. In this work, we demonstrate Helium Ion
      Microscopy (HIM) as a tool for imaging and quantification of pores in
      industrially relevant SiO2 catalyst supports. We start with the fundamental
      principles of ion-sample interaction, and build on this knowledge to
      experimentally observe and quantify surface pores by using the HIM and image data
      analytics. We contrast our experimental results to gas absorption and demonstrate
      full statistical agreement between two techniques. The principles behind the
      theoretical, experimental, and analytical framework presented herein offer an
      automated framework for visualization and quantification of pore structures in a
      wide variety of materials.

PMID- 29227632
TI  - Soluble Molecularly Imprinted Polymer-Based Potentiometric Sensor for
      Determination of Bisphenol AF.
AB  - Molecularly imprinted polymer (MIP)-based polymeric membrane potentiometric
      sensors have been successfully developed for determination of organic compounds
      in their ionic and neutral forms. However, most of the MIP receptors in
      potentiometric sensors developed so far are insoluble and cannot be well
      dissolved in the polymeric membranes. The heterogeneous molecular recognitions
      between the analytes and MIPs in the membranes are inefficient due to the less
      available binding sites of the MIPs. Herein we describe a novel polymeric
      membrane potentiometric sensor using a soluble MIP (s-MIP) as a receptor. The s
      MIP is synthesized by the swelling of the traditional MIP at a high temperature.
      The obtained MIP can be dissolved in the plasticized polymeric membrane for
      homogeneous binding of the imprinted polymer to the target molecules. By using
      neutral bisphenol AF as a model, the proposed method exhibits an improved
      sensitivity compared to the conventional MIP-based sensor with a lower detection
      limit of 60 nM. Moreover, the present sensor exhibits an excellent selectivity
      over other phenols. We believe that s-MIPs can provide an appealing substitute
      for the traditional insoluble MIP receptors in the development of polymeric
      membrane-based electrochemical and optical sensors.

PMID- 29227633
TI  - A Distal Loop Controls Product Release and Chemo- and Regioselectivity in
      Cytochrome P450 Decarboxylases.
AB  - Cytochrome P450 OleT utilizes hydrogen peroxide (H2O2) to catalyze the
      decarboxylation or hydroxylation of fatty acid (FA) substrates. Both reactions
      are initiated through the abstraction of a substrate hydrogen atom by the high
      valent iron-oxo intermediate known as Compound I. Here, we specifically probe the
      influence of substrate coordination on OleT reaction partitioning through the
      combined use of fluorescent and electron paramagnetic resonance (EPR)-active FA
      probes and mutagenesis of a structurally disordered F-G loop that is distal from
      the heme-iron active site. Both probes are efficiently metabolized by OleT and
      efficiently trigger the formation of Compound I. Transient fluorescence and EPR
      reveal a slow product release step, mediated by the F-G loop, that limits OleT
      turnover. A single-amino acid change or excision of the loop reveals that this
      region establishes critical interactions to anchor FA substrates in place. The
      stabilization afforded by the F-G loop is essential for regulating regiospecific
      C-H abstraction and allowing for efficient decarboxylation to occur. These
      results highlight a regulatory strategy whereby the fate of activated oxygen
      species can be controlled at distances far removed from the site of chemistry.

PMID- 29227634
TI  - Release of Particulate Iron Sulfide during Shale-Fluid Interaction.
AB  - During hydraulic fracturing, a technique often used to extract hydrocarbons from
      shales, large volumes of water are injected into the subsurface. Although the
      injected fluid typically contains various reagents, it can become further
      contaminated by interaction with minerals present in the rocks. Pyrite, which is
      common in organic-rich shales, is a potential source of toxic elements, including
      arsenic and lead, and it is generally thought that for these elements to become
      mobilized, pyrite must first dissolve. Here, we use atomic force microscopy and
      environmental scanning electron microscopy to show that during fluid-rock
      interaction, the dissolution of carbonate minerals in Eagle Ford shale leads to
      the physical detachment, and mobilization, of embedded pyrite grains. In
      experiments carried out over a range of pH, salinity, and temperature we found
      that in all cases pyrite particles became detached from the shale surfaces. On
      average, the amount of pyrite detached was equivalent to 6.5 * 10-11 mol m-2 s-1,
      which is over an order of magnitude greater than the rate of pyrite oxidation
      expected under similar conditions. This result suggests that mechanical
      detachment of pyrite grains could be an important pathway for the mobilization of
      arsenic in hydraulic fracturing operations and in groundwater systems containing
      shales.

PMID- 29227635
TI  - Small Bioactive Peptides for Biomaterials Design and Therapeutics.
AB  - This review is aimed to provide a concise yet extensive survey of key short
      bioactive peptide sequences for a range of applications ranging from biomaterials
      development to peptides with therapeutic uses. The following are considered: cell
      adhesion motifs, structural peptides, cell-penetrating and tumor-homing peptides,
      antimicrobial peptides, peptide hormones, growth factors and matrix
      metalloprotease substrates, neuropeptides, amyloid peptides, antioxidant
      peptides, peptide affinity tags, anticancer peptides, and others. This review
      provides a convenient resource, summarizing a broad range of important sequences
      with great utility as a resource concerning both small peptide drugs and also
      novel biofunctional peptide-based materials.

PMID- 29227636
TI  - Strategies To Assemble Catenanes with Multiple Interlocked Macrocycles.
AB  - As a major class of mechanically interlocked molecules, not only are catenanes
      topologically intriguing targets that challenge the chemical synthesis to the
      efficient formation of mechanical bonds, but also the mechanical properties
      arising from the topology offer unique and attractive features for the
      development of novel functional molecular materials. Despite advancements in
      templated methods for different types of interlocked architectures, [ n]catenane
      possessing multiple numbers of interlocked macrocycles still remains a difficult
      synthetic target with very few reported examples. If the unique mechanical
      properties of catenanes are to be fully exploited, reliable, controllable, and
      efficient strategies for accessing [ n]catenanes will be necessary. In this
      Viewpoint, challenges, considerations, and strategies to [ n]catenanes are
      discussed.

PMID- 29227637
TI  - Urban Organic Aerosol Exposure: Spatial Variations in Composition and Source
      Impacts.
AB  - We conducted a mobile sampling campaign in a historically industrialized terrain
      (Pittsburgh, PA) targeting spatial heterogeneity of organic aerosol. Thirty-six
      sampling sites were chosen based on stratification of traffic, industrial source
      density, and elevation. We collected organic carbon (OC) on quartz filters,
      quantified different OC components with thermal-optical analysis, and grouped
      them based on volatility in decreasing order (OC1, OC2, OC3, OC4, and pyrolyzed
      carbon (PC)). We compared our ambient OC concentrations (both gas and particle
      phase) to similar measurements from vehicle dynamometer tests, cooking emissions,
      biomass burning emissions, and a highway traffic tunnel. OC2 and OC3 loading on
      ambient filters showed a strong correlation with primary emissions while OC4 and
      PC were more spatially homogeneous. While we tested our hypothesis of OC2 and OC3
      as markers of fresh source exposure for Pittsburgh, the relationship seemed to
      hold at a national level. Land use regression (LUR) models were developed for the
      OC fractions, and models had an average R2 of 0.64 (SD = 0.09). The paper
      demonstrates that OC2 and OC3 can be useful markers for fresh emissions, OC4 is a
      secondary OC indicator, and PC represents both biomass burning and secondary
      aerosol. People with higher OC exposure are likely inhaling more fresh OC2 and
      OC3, since secondary OC4 and PC varies much less drastically in space or with
      local primary sources.

PMID- 29227638
TI  - Byproduct-Free Intact Modification of Insulin by Cholesterol End-Modified
      Poly(ethylene glycol) for in Vivo Protein Delivery.
AB  - Insulin is a key peptide hormone used for the treatment of both type I and type
      II diabetes. To maximize the effect of the treatment of these diseases, the
      addition of poly(ethylene glycol) (PEGylation) methods for the insulin are widely
      developed. Here, to make these PEGylation methods the simplest, we report the
      byproduct-free intact modification of insulin by cholesterol end-modified
      poly(ethylene glycol) with urethane, propyl, and methoxy groups (that is, Chol-U
      Pr-mPEG). The noncovalent PEGylation by the Chol-U-Pr-mPEG has been achieved by
      the simple mixing of insulin with the Chol-U-Pr-mPEG in aqueous solution,
      followed by freeze-drying. The formation of the Chol-U-Pr-mPEG/insulin complex
      has proceeded without byproducts, such as N-hydroxysuccinimide, formed by the
      conventional covalent PEGylation using an active ester group. The byproduct-free
      PEGylation has preserved insulin conformation as well as primary structure. The
      intact PEGylation has protected insulin from hydrolysis by protease. The
      resulting insulin modified by the Chol-U-Pr-mPEG has sustainably suppressed the
      level of blood glucose, as compared to naked insulin, in mice. Consequently, the
      Chol-U-Pr-mPEG/insulin complex formation offers the byproduct-free intact
      PEGylation of insulin for in vivo protein delivery.

PMID- 29227639
TI  - Structural Behavior of Natural Silicate-Carbonate Spurrite Mineral,
      Ca5(SiO4)2(CO3), under High-Pressure, High-Temperature Conditions.
AB  - We report on high-pressure and high-temperature angle-dispersive synchrotron X
      ray diffraction and high-pressure Raman data up to 27 GPa and 700 K for natural
      silicate carbonate Ca5(SiO4)2(CO3) spurrite mineral. No phase transition was
      found in the studied P-T range. The room-temperature bulk modulus of spurrite
      using Ne as the pressure-transmitting medium is B0 = 77(1) GPa with a first
      pressure derivative of B0' = 5.9(2). The structure compression is highly
      anisotropic, the b axis being approximately 30% more compressible than the a and
      c axes. The volumetric thermal expansivity value around 8 GPa was estimated to be
      4.1(3) * 10-5 K-1. A comparison with intimately related minerals CaCO3 calcite
      and aragonite and beta-Ca2SiO4 larnite shows that, as the composition and
      structural features of spurrite suggest, its compressibility and thermal
      expansivity lie between those of the silicate and carbonate end members. The
      crystal chemistry and thermodynamic properties of spurrite are discussed.

PMID- 29227640
TI  - Raman Spectroscopy Applied to Parathyroid Tissues: A New Diagnostic Tool to
      Discriminate Normal Tissue from Adenoma.
AB  - Primary hyperparathyroidism is an endocrine disorder characterized by autonomous
      production of parathyroid hormone. Patients with the symptomatic disease should
      be referred for parathyroidectomy. However, the distinction between the
      pathological condition and the benign one is very challenging in the surgical
      setting; therefore, accurate recognition is important to ensure success during
      minimally invasive surgery. At present, all intraoperative techniques
      significantly increase surgical time and, consequently, cost. In this proof-of
      concept study, Raman microscopy was used to differentiate between healthy
      parathyroid tissue and parathyroid adenoma from 18 patients. The data showed
      different spectroscopic features for the two main tissue types of healthy and
      adenoma. Moreover, the parathyroid adenoma subtypes (chief cells and oxyphil
      cells) were characterized by their own Raman spectra. The partial least-squares
      discriminant analysis (PLS-DA) model built to discriminate healthy from
      adenomatous parathyroid tissue was able to correctly classify all samples in the
      calibration and validation data sets, providing 100% prediction accuracy. The PLS
      DA model built to discriminate chief cell adenoma from oxyphil cell adenoma
      allowed us to correctly classify >99% of the spectra during calibration and cross
      validation and to correctly predict 100% of oxyphil and 99.8% of chief cells in
      the external validation data set. The results clearly demonstrate the great
      potential of Raman spectroscopy. The final goal would be development of a Raman
      portable fiber probe device for intraoperative optical biopsy, both to improve
      the surgical success rate and reduce surgical cost.

PMID- 29227641
TI  - Reversible and Sensitive Hg2+ Detection by a Cell-Permeable Ytterbium Complex.
AB  - A cell-permeable ytterbium complex shows reversible binding with Hg2+ in aqueous
      solution and in vitroby off-on visible and NIR emission. The fast response and
      150 nM sensitivity of Hg2+ detection is based upon FRET and the lanthanide
      antenna effect. The reversible Hg2+ detection can be performed in vitro, and the
      binding mechanism is suggested by NMR employing the motif structure in a La
      complex and by DFT calculations.

PMID- 29227642
TI  - X-rays in the Cryo-Electron Microscopy Era: Structural Biology's Dynamic Future.
AB  - Over the past several years, single-particle cryo-electron microscopy (cryo-EM)
      has emerged as a leading method for elucidating macromolecular structures at near
      atomic resolution, rivaling even the established technique of X-ray
      crystallography. Cryo-EM is now able to probe proteins as small as hemoglobin (64
      kDa) while avoiding the crystallization bottleneck entirely. The remarkable
      success of cryo-EM has called into question the continuing relevance of X-ray
      methods, particularly crystallography. To say that the future of structural
      biology is either cryo-EM or crystallography, however, would be misguided.
      Crystallography remains better suited to yield precise atomic coordinates of
      macromolecules under a few hundred kilodaltons in size, while the ability to
      probe larger, potentially more disordered assemblies is a distinct advantage of
      cryo-EM. Likewise, crystallography is better equipped to provide high-resolution
      dynamic information as a function of time, temperature, pressure, and other
      perturbations, whereas cryo-EM offers increasing insight into conformational and
      energy landscapes, particularly as algorithms to deconvolute conformational
      heterogeneity become more advanced. Ultimately, the future of both techniques
      depends on how their individual strengths are utilized to tackle questions at the
      frontiers of structural biology. Structure determination is just one piece of a
      much larger puzzle: a central challenge of modern structural biology is to relate
      structural information to biological function. In this perspective, we share
      insight from several leaders in the field and examine the unique and
      complementary ways in which X-ray methods and cryo-EM can shape the future of
      structural biology.

PMID- 29227644
TI  - Molecular Building Block-Based Electronic Charges for High-Throughput Screening
      of Metal-Organic Frameworks for Adsorption Applications.
AB  - Metal-organic frameworks (MOFs) are porous crystalline materials with attractive
      properties for gas separation and storage. Their remarkable tunability makes it
      possible to create millions of MOF variations but creates the need for fast
      material screening to identify promising structures. Computational high
      throughput screening (HTS) is a possible solution, but its usefulness is tied to
      accurate predictions of MOF adsorption properties. Accurate adsorption
      simulations often require an accurate description of electrostatic interactions,
      which depend on the electronic charges of the MOF atoms. HTS-compatible methods
      to assign charges to MOF atoms need to accurately reproduce electrostatic
      potentials (ESPs) and be computationally affordable, but current methods present
      an unsatisfactory trade-off between computational cost and accuracy. We
      illustrate a method to assign charges to MOF atoms based on ab initio
      calculations on MOF molecular building blocks. A library of building blocks with
      built-in charges is thus created and used by an automated MOF construction code
      to create hundreds of MOFs with charges "inherited" from the constituent building
      blocks. The molecular building block-based (MBBB) charges are similar to REPEAT
      charges-which are charges that reproduce ESPs obtained from ab initio
      calculations on crystallographic unit cells of nanoporous crystals-and thus
      similar predictions of adsorption loadings, heats of adsorption, and Henry's
      constants are obtained with either method. The presented results indicate that
      the MBBB method to assign charges to MOF atoms is suitable for use in
      computational high-throughput screening of MOFs for applications that involve
      adsorption of molecules such as carbon dioxide.

PMID- 29227643
TI  - Structure-Activity Relationship Studies on a Series of 3alpha-[Bis(4
      fluorophenyl)methoxy]tropanes and 3alpha-[Bis(4-fluorophenyl)methylamino]tropanes
      As Novel Atypical Dopamine Transporter (DAT) Inhibitors for the Treatment of
      Cocaine Use Disorders.
AB  - The development of medications to treat cocaine use disorders has thus far defied
      success, leaving this patient population without pharmacotherapeutic options. As
      the dopamine transporter (DAT) plays a prominent role in the reinforcing effects
      of cocaine that can lead to addiction, atypical DAT inhibitors have been
      developed that prevent cocaine from binding to DAT, but they themselves are not
      cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and
      based on its pharmacological profile, the lead compound 10a was evaluated in
      phase I metabolic stability studies in mouse liver microsomes and compared to
      cocaine in locomotor activity and drug discrimination paradigms in mice. A
      molecular dynamic simulation study supported the hypothesis that atypical DAT
      inhibitors have similar binding poses at DAT in a conformation that differs from
      that of cocaine. Such differences may ultimately contribute to their unique
      behavioral profiles and potential for development as cocaine use disorder
      therapeutics.

PMID- 29227645
TI  - Structural Trends in Monoboronyl Compounds: Analysis of the Interaction of Second
      Row Elements with BO.
AB  - A theoretical study of the monoboronyl compounds of second-row elements, [XBO] (X
      = Na, Si, P, S, Cl), has been carried out. It is observed that the preference for
      the XBO arrangement is higher when moving to the right of the period. In the case
      of sodium monoboronyl three minima were characterized, all lying rather close in
      energy: linear NaBO, linear NaOB, and an L-shaped structure. Linear NaBO and the
      L-shaped structure are nearly isoenergetic, whereas linear NaOB is located 2.11
      kcal/mol above linear NaBO. The barrier for the conversion of the L-shaped
      structure into linear NaBO is about 5.1 kcal/mol, suggesting that both species
      could be potential targets for experimental detection. For silicon monoboronyl,
      two minima, linear SiBO and linear SiOB, are found, the latter lying about 13
      kcal/mol above SiBO. The barrier for the isomerization of SiOB into SiBO is
      estimated to be 11.4 kcal/mol. For phosphorus, sulfur, and chlorine monoboronyls
      the linear XBO isomer is clearly the most stable one, and the barriers for the
      conversion into XOB species are relatively high, suggesting that quite likely the
      linear XBO isomer should be the main experimental target. All studied
      monoboronyls are relatively stable, with dissociation energies increasing from
      left to right of the second-row (69.8 kcal/mol for NaBO and 118.98 kcal/mol for
      ClBO). An analysis of the bonding for second-row monoboronyls has been carried
      out, emphasizing the different characteristics of the X-B and X-O bonds along the
      second row.

PMID- 29227646
TI  - Direct Observation of Carbohydrate Hydroxyl Protons in Hydrogen Bonds with a
      Protein.
AB  - Hydroxyl proton resonances of uniformly 13C-labeled Manalpha(1-2)Manalpha(1
      2)ManalphaOMe (Man3) bound to cyanovirin-N (CV-N) were detected at ambient
      temperature in aqueous solution by NMR spectroscopy. The directions of the
      hydroxyl groups were determined on the basis of NOEs, and a previously unknown
      hydrogen-bonding network between Man3 and CV-N was discovered. This is the first
      report on detecting hydroxyl protons of a protein-bound carbohydrate in aqueous
      solution by NMR. Approaches such as those presented here may open the door for
      accurately determining intermolecular hydrogen bonds in carbohydrate-protein
      complexes.

PMID- 29227647
TI  - Anti-inflammatory Dimeric 2-(2-Phenylethyl)chromones from the Resinous Wood of
      Aquilaria sinensis.
AB  - Sixteen new 2-(2-phenylethyl)chromone dimers, including four pairs of enantiomers
      (1a/1b, 3a/3b, 6a/6b, and 8a/8b), along with eight optically pure analogues (2,
      4, 5, 7, and 9-12) were isolated from the resinous wood of Aquilaria sinensis.
      Their structures were determined by extensive spectroscopic analysis (1D and 2D
      NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1-10
      feature an unusual 3,4-dihydro-2 H-pyran ring linkage connecting two 2-(2
      phenylethyl)chromone monomeric units, while compounds 11 and 12 possess an
      unprecedented 6,7-dihydro-5 H-1,4-dioxepine moiety in their structures. A
      putative biosynthetic pathway of the representative structures via a diepoxy
      derivative of a chromone with a nonoxygenated A-ring is also proposed. Compounds
      1a/1b, 2, 3a/3b, 5, 7, 8a/8b, and 10-12 exhibited significant inhibition of
      nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50
      values in the range 7.0-12.0 MUM.

PMID- 29227648
TI  - Quinazolinone-Based Anticancer Agents: Synthesis, Antiproliferative SAR,
      Antitubulin Activity, and Tubulin Co-crystal Structure.
AB  - Quinazolinone-based anticancer agents were designed, decorated with functional
      groups from a 2-methoxyestradiol-based microtubule disruptor series,
      incorporating the aryl sulfamate motif of steroid sulfatase (STS) inhibitors. The
      steroidal AB-ring system was mimicked, favoring conformations with an N-2
      substituent occupying D-ring space. Evaluation against breast and prostate tumor
      cell lines identified 7b with DU-145 antiproliferative activity (GI50 300 nM). A
      preliminary structure-activity relationship afforded compounds (e.g., 7j GI50 50
      nM) with activity exceeding that of the parent. Both 7b and 7j inhibit tubulin
      assembly in vitro and colchicine binding, and 7j was successfully co-crystallized
      with the alphabeta-tubulin heterodimer as the first of its class, its sulfamate
      group interacting positively at the colchicine binding site. Microtubule
      destabilization by 7j is likely achieved by preventing the curved-to-straight
      conformational transition in alphabeta-tubulin. Quinazolinone sulfamates
      surprisingly showed weak STS inhibition. Preliminary in vivo studies in a
      multiple myeloma xenograft model for 7b showed oral activity, confirming the
      promise of this template.

PMID- 29227649
TI  - Regenerative Glycosylation.
AB  - Previously, we communicated 3,3-difluoroxindole (HOFox)-mediated glycosylations
      wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key
      intermediates. Both the in situ synthesis from the corresponding glycosyl
      bromides and activation of the OFox imidates could be conducted in a regenerative
      fashion. Herein, we extend this study to the synthesis of various glycosidic
      linkages using different sugar series. The main outcome of this study relates to
      enhanced yields and/or reduced reaction times of glycosylations. The effect of
      HOFox-mediated reactions is particularly pronounced in case of unreactive
      glycosyl donors and/or glycosyl acceptors. A multistep regenerative synthesis of
      oligosaccharides is also reported.

PMID- 29227650
TI  - Molecular Evidence for Catechin Synthesis and Accumulation in Tea Buds (Camellia
      sinensis).
AB  - Early spring buds of the Camellia sinensis variety Shuchazao were separated into
      two parts, including the shoot tip (ST) and non-expanded young leaves (YL), in
      which the synthesis and accumulation of catechins in the two parts were assessed
      by high-performance liquid chromatography (HPLC), p-dimethylaminocinnamaldehyde
      (DMACA) staining, quantitative real-time polymerase chain reaction (qRT-PCR), and
      in situ hybridization. HPLC showed that (-)-epigallocatechin-3-gallate (EGCG) and
      (-)-epicatechin-3-gallate (ECG) amounts in YL were increased significantly by
      74.0 and 71.8%, respectively. The results of DMACA staining indicated that
      catechins in buds accumulated mainly in mesophyll cells and the bud shaft of YL.
      Meanwhile, qRT-PCR demonstrated that the relative expression levels of genes
      related to flavonoid metabolism, including CsPAL1, CsC4H1, CsC4H2, CsCHS2,
      CsF3'5'H1, CsDFR1, CsDFR2, and CsANR1, were significantly higher in YL than in
      the ST. In situ hybridization revealed that CsDFR1, CsDFR2, CsLAR, and CsANR1
      were expressed in leaf primordia and YL but not in the apical meristem. These
      findings highlight the synthesis and accumulation patterns of catechins in
      different parts of the ST in C. sinensis, providing a theoretical basis for the
      assessment of synthesis, accumulation, and transfer patterns of catechins in tea
      plants.

PMID- 29227651
TI  - Total Syntheses of Scaparvins B, C, and D Enabled by a Key C-H Functionalization.
AB  - The clerodane diterpene family possesses an impressive range of bioactivities and
      high synthetic challenge due to their unique amalgamation of rings,
      stereocenters, and oxygenation. Herein, we disclose the first total syntheses of
      three members, scaparvins B, C, and D, through a route fueled by several
      chemoselective and carefully orchestrated steps. One such operation is a tailored
      late-stage C-H functionalization converting a carboxylic acid into a lactone
      through the oxidation of a tertiary C-H bond under conditions that minimize
      epoxidation of an alkene. This step, among others, afforded critical
      functionality to complete the targets. In addition, use of an appropriate chiral
      catalyst with a Rawal diene renders the sequence enantioselective.

PMID- 29227652
TI  - Expedient Synthesis of Highly Functionalized Abnormal Carbenegold(I) Complexes.
AB  - The reaction of 4-substituted imidazol-2-ylidenes with various electrophiles
      produces a series of 2,4-functionalized imidazolium salts. Subsequent metalation
      of these precursors using AuCl(SMe2) provides the first examples of highly
      functionalized abnormal carbenegold(I) complexes. The present protocol introduces
      a new strategy for the synthesis of metallic abnormal carbenes featuring diverse
      functional groups.

PMID- 29227653
TI  - Structural Stability and Evolution of Medium-Sized Tantalum-Doped Boron Clusters:
      A Half-Sandwich-Structured TaB12- Cluster.
AB  - Transition-metal (TM)-doped boron clusters have received considerable attention
      in recent years, in part, because of their remarkable size-dependent structural
      and electronic properties. However, the structures of medium-sized boron clusters
      doped with TM atoms are still not well-known because of the much increased
      complexity of the potential surface as well as the rapid increase in the number
      of low-energy isomers, which are the challenges in cluster structural searches.
      Here, by means of an unbiased structure search, we systematically investigated
      the structural evolution of medium-sized tantalum-doped boron clusters, TaBn0/-
      (n = 10-20). The results revealed that TaBn0/- (n = 10-15) clusters adopt half
      sandwich molecular geometries, with the notable exception of TaB10-, while for n
      = 16-18 and 19-20, the lowest-energy clusters are characterized by drum-type
      geometries and tubular molecules with two B atoms on the top, respectively. Good
      agreement between the calculated and experimental photoelectron spectra strongly
      support the validity of our global minimum structures. Molecular orbital and
      adaptive natural density partitioning analyses indicate that the enhanced
      stability of half-sandwich TaB12- is due to the strong interaction of the Ta atom
      (5d orbitals) with surrounding B atoms (2p orbitals) and sigma B-B bonds in the
      B12 moiety.

PMID- 29227654
TI  - Synergistic Chemopreventive and Therapeutic Effects of Co-drug UA-Met:
      Implication in Tumor Metastasis.
AB  - The anticancer properties of ursolic acid (UA) and metformin (Met) have been well
      demonstrated. However, whether these compounds can act synergistically to prevent
      and treat cancer is not known. We present in this study, the synergism between UA
      and Met, and that of a new codrug made of UA and Met (UA-Met) against several
      cancer cell lines. The combination of high concentration of UA (25, 50, 75, 100
      MUM) and Met (5, 10, 20, 40 mM) resulted in synergetic cytotoxicity on MDA-MB-231
      and MCF-7 cells (CI < 0.8). Molecular and cellular studies showed that codrug UA
      Met significantly inhibited the invasion (~55.3 +/- 2.74%) and migration (~52.4
      +/- 1.57%) of TGF-beta induced breast cancer MDA-MB-231 and MCF-7 cells in vitro
      at low concentration of 10 MUM. These effects were accompanied by down-regulation
      of CXCR4, uPA, vimentin, E-cadherin, N-cadherin, and MMP-2/9 proteins expression
      and regulation of the AMPK/m-TOR signaling pathways as expected from UA and Met.
      Moreover, UA-Met could reduce the progression of pulmonary metastasis by 4T1
      cells (63.4 +/- 3.52%) without influencing the glucose blood level in mice. Our
      study suggests that the codrug UA-Met is safe and effective in preventing cancer
      metastasis and possibly treatment of cancer.

PMID- 29227655
TI  - Hydrazine Capture and N-N Bond Cleavage at Iron Enabled by Flexible Appended
      Lewis Acids.
AB  - Incorporation of two 9-borabicyclo[3.3.1]nonyl substituents within the secondary
      coordination sphere of a pincer-based Fe(II) complex provides Lewis acidic sites
      capable of binding 1 or 2 equiv of N2H4. Reduction of the 1:1 Fe:N2H4 species
      affords a rare Fe(NH2)2 complex in which the amido ligands are stabilized through
      interactions with the appended boranes. The NH2 units can be released as NH3 upon
      protonation and exchanged with exogenous N2H4.

PMID- 29227656
TI  - Artocarmins G-M, Prenylated 4-Chromenones from the Stems of Artocarpus rigida and
      Their Tyrosinase Inhibitory Activities.
AB  - Phytochemical analysis of an EtOAc extract of the stems of Artocarpus rigida led
      to the identification of seven new prenylated 4-chromenones, artocarmins G-M (1
      7), and nine known compounds (8-17). Their structures were identified based on
      physical data analysis. In the tyrosinase inhibitory activity test,
      norartocarpetin (8) displayed the strongest effect, with an IC50 value of 0.023
      MUM.

PMID- 29227657
TI  - Density-Functional Tight-Binding Molecular Dynamics Simulations of Excess Proton
      Diffusion in Ice Ih, Ice Ic, Ice III, and Melted Ice VI Phases.
AB  - The structural, dynamical, and energetic properties of the excess proton in ice
      were studied using density-functional tight-binding molecular dynamics
      simulations. The ice systems investigated herein consisted of low-density
      hexagonal and cubic crystalline variants (ice Ih and Ic) and high-density
      structures (ice III and melted ice VI). Analysis of the temperature dependence of
      radial distribution function and bond order parameters served to characterize the
      distribution and configuration of hundreds of water molecules in a unit cell. We
      confirmed that ice Ih and Ic possess higher hexagonal symmetries than ice III and
      melted ice VI. The estimated Grotthuss shuttling diffusion coefficients in ice
      were larger than that of liquid water, indicating a slower proton diffusion
      process in high-density structures than in low-density systems. The energy
      barriers calculated on the basis of the Arrhenius plot of diffusion coefficients
      were in reasonable agreement with experimental measurement for ice Ih.
      Furthermore, the energy barriers for high-density structures were several times
      larger than those of low-density systems. The simulation results were likely
      related to the suppression of proton transfer in disordered water configurations,
      in particular, ice with low hexagonal symmetry.

PMID- 29227658
TI  - Ion Speciation and Transport Properties of LiTFSI in 1,3-Dioxolane Solutions: A
      Case Study for Li-S Battery Applications.
AB  - Lithium-sulfur battery is considered to be one of the main candidates for "post
      lithium-ion" battery generation because of its high theoretical specific capacity
      and inherently low cost. The role of electrolyte is particularly important in
      this system, and remarkable battery performances have been reported by tuning the
      amount of salt in the electrolyte. To further understand the reasons for such
      improvements, we chose the lithium bis(trifluoromethanesulfonyl)imide in 1,3
      dioxolane electrolyte as a model salt-solvent system for a systematic study of
      conductivity and viscosity over a wide range of concentration from 10-5 up to 5
      m. The experimental results, discussed and interpreted with reference to the
      theory of electrolyte conductance, lead to the conclusion that triple ion
      formation is responsible for the highest molal conductivity values before
      reaching the maximum at 1.25 m. At higher concentrations, the molal conductivity
      drops quickly because of a rapid increase in viscosity and the salt-solvent
      system can be treated as a diluted form of molten salt.

PMID- 29227659
TI  - Cationic Gemini Surfactant-Plasmid Deoxyribonucleic Acid Condensates as a Single
      Amphiphilic Entity.
AB  - A critical aggregate concentration for the surfactant-DNA "complex" or
      "condensate" consisting of the 16-3-16 gemini surfactant and circular plasmid DNA
      was determined using surface tensiometry, dynamic light scattering, and
      conductometry. This surfactant-DNA complex acts as an amphiphile itself, for
      example, decreasing the surface tension of water until a critical concentration
      is reached. The evidence presented here introduces a new way of considering these
      surfactant-DNA condensates, not simply as aggregates in solution but as surface
      active agents in their own right. At concentrations below the critical aggregate
      concentration, there is some dissociation of surfactant molecules from the
      condensate, creating a more "loose" or "relaxed" complex; however, at and above
      the critical aggregate concentration, the surfactant-DNA system forms smaller and
      more uniformly distributed condensates once again. This behavior is analogous to
      demicellization/micellization that occurs in typical surfactant systems.

PMID- 29227660
TI  - A Two-Dimensional Manganese Gallium Nitride Surface Structure Showing
      Ferromagnetism at Room Temperature.
AB  - Practical applications of semiconductor spintronic devices necessitate
      ferromagnetic behavior at or above room temperature. In this paper, we
      demonstrate a two-dimensional manganese gallium nitride surface structure (MnGaN
      2D) which is atomically thin and shows ferromagnetic domain structure at room
      temperature as measured by spin-resolved scanning tunneling microscopy and
      spectroscopy. Application of small magnetic fields proves that the observed
      magnetic domains follow a hysteretic behavior. Two initially oppositely oriented
      MnGaN-2D domains are rotated into alignment with only 120 mT and remain mostly in
      alignment at remanence. The measurements are further supported by first
      principles theoretical calculations which reveal highly spin-polarized and spin
      split surface states with spin polarization of up to 95% for manganese local
      density of states.

PMID- 29227661
TI  - High-Resolution Photoelectron Imaging of Cryogenically-Cooled C59N- and (C59N)22-
      Azafullerene Anions.
AB  - We report a photoelectron imaging study of cryogenically cooled C59N- and
      (C59N)22- anions produced from electrospray ionization. High-resolution
      photoelectron spectra are obtained for C59N- for the first time, allowing seven
      vibrational frequencies of the C59N azafullerene to be measured. The electron
      affinity of C59N is determined accurately to be 3.0150 +/- 0.0007 eV. The
      observed vibrational features are understood on the basis of calculated
      frequencies and compared with those of C60 and C59HN. The photoelectron image of
      (C59N)22-, which has the same mass/charge ratio as C59N-, is also observed,
      allowing the second electron affinity of the (C59N)2 azafullerene dimer to be
      measured as 1.20 +/- 0.05 eV. The intramolecular Coulomb repulsion of the
      (C59N)22- dianion is estimated to be 1.96 eV and is investigated theoretically
      using the electron density difference between (C59N)22- and (C59N)2.

PMID- 29227662
TI  - Asymmetric Synthesis of 3,4-Dihydroquinolin-2-ones via a Stereoselective
      Palladium-Catalyzed Decarboxylative [4 + 2]- Cycloaddition.
AB  - An efficient, palladium-catalyzed, decarboxylative [4 + 2]-cycloaddition of 4
      vinyl benzoxazinanones with carboxylic acids has been developed with the
      employment of P-chiral monophosphorus ligand BI-DIME, affording a series of
      structurally diverse 3,4-dihydroquinolin-2-ones bearing two contiguous
      stereogenic centers in moderate to good yields with good to excellent
      stereoselectivities.

PMID- 29227663
TI  - Retraction of "Access to Cyclobutadienes via an Organocatalytic Dienamine-Iminium
      Allenamine Cascade Approach".

PMID- 29227664
TI  - Deep-Blue High-Efficiency TTA OLED Using Para- and Meta-Conjugated
      Cyanotriphenylbenzene and Carbazole Derivatives as Emitter and Host.
AB  - Elaboration of the appropriate host materials proved to be not less important for
      the fabrication of a highly efficient OLED than the design of emitters. In the
      present work, we show how by simple variation of molecular structure both blue
      emitters exhibiting delayed fluorescence and ambipolar high triplet energy hosts
      can be obtained. The compounds with a para-junction revealed higher thermal
      stability (TID up to 480  degrees C), lower ionization potentials (5.51-5.60 eV),
      exclusively hole transport, and higher photoluminescence quantum efficiencies
      (0.90-0.97). Meta-linkage leads to ambipolar charge transport and higher triplet
      energies (2.82 eV). Introduction of the accepting nitrile groups in the para
      position induces intensive delayed fluorescence via a triplet-triplet
      annihilation up-conversion mechanism. By utilization of the para-substituted
      derivative as an emitter and the meta-substituted isomer as the host, a deep-blue
      OLED with the external quantum efficiency of 14.1% was fabricated.

PMID- 29227665
TI  - Rare Sulfur-Containing Compounds, Kujounins A1 and A2 and Allium Sulfoxide A1,
      from Allium fistulosum 'Kujou'.
AB  - Three sulfur-containing compounds, kujounins A1 (1) and A2 (2) and allium
      sulfoxide A1 (3), were isolated from the acetone extract of Allium fistulosum
      'Kujou'. Their chemical structures were elucidated on the basis of
      physicochemical evidence, including X-ray crystallographic data. Compounds 1 and
      2 possess three rings and an acetal structure and were obtained as complex
      compounds having disulfide and monosaccharide moieties. On the other hand,
      compound 3 has a thiolane skeleton derived from allicin. Naturally occurring
      compounds 1-3 have rare molecular skeletons. This study is the first to determine
      the absolute configuration of thiolane-type compounds.

PMID- 29227666
TI  - Nonlinear Light Mixing by Graphene Plasmons.
AB  - Graphene is known to possess strong optical nonlinearity which turned out to be
      suitable for creation of efficient saturable absorbers in mode locked fiber
      lasers. Nonlinear response of graphene can be further enhanced by the presence of
      graphene plasmons. Here, we report a novel nonlinear effect observed in
      nanostructured graphene which comes about due to excitation of graphene plasmons.
      We experimentally detect and theoretically explain enhanced mixing of near
      infrared and mid-infrared light in arrays of graphene nanoribbons. Strong
      compression of light by graphene plasmons implies that the described effect of
      light mixing is nonlocal in nature and orders of magnitude larger than the
      conventional local graphene nonlinearity. Both second and third order nonlinear
      effects were observed in our experiments with the recalculated third-order
      nonlinearity coefficient reaching values of 4.5 * 10-6 esu. The suggested effect
      could be used in variety of applications including nonlinear light modulators,
      light multiplexers, light logic, and sensing devices.

PMID- 29227667
TI  - Oxidative Dehydrogenative [2 + 3]-Cyclization of Glycine Esters with Aziridines
      Leading to Imidazolidines.
AB  - Oxidative dehydrogenative [2 + 3]-cyclization of glycine derivatives with N
      sulfonylaziridines is described. A series of complex imidazolidines were produced
      under mild and simple reaction conditions. A mechanism involving an unusual acid
      promoted auto-oxidation is proposed.

PMID- 29227668
TI  - BOCS: Bottom-up Open-source Coarse-graining Software.
AB  - We present the BOCS toolkit as a suite of open source software tools for
      parametrizing bottom-up coarse-grained (CG) models to accurately reproduce
      structural and thermodynamic properties of high-resolution models. The BOCS
      toolkit complements available software packages by providing robust
      implementations of both the multiscale coarse-graining (MS-CG) force-matching
      method and also the generalized-Yvon-Born-Green (g-YBG) method. The g-YBG method
      allows one to analyze and to calculate MS-CG potentials in terms of structural
      correlations. Additionally, the BOCS toolkit implements an extended ensemble
      framework for optimizing the transferability of bottom-up potentials, as well as
      a self-consistent pressure-matching method for accurately modeling the pressure
      equation of state for homogeneous systems. We illustrate these capabilities by
      parametrizing transferable potentials for CG models that accurately model the
      structure, pressure, and compressibility of liquid alkane systems and by
      quantifying the role of many-body correlations in determining the calculated pair
      potential for a one-site CG model of liquid methanol.

PMID- 29227669
TI  - Electron-Hole-Pair-Induced Vibrational Energy Relaxation of Rhenium Catalysts on
      Gold Surfaces.
AB  - A combination of time-resolved vibrational spectroscopy and density functional
      theory techniques have been applied to study the vibrational energy relaxation
      dynamics of the Re(4,4'-dicyano-2,2'-bipyridine)(CO)3Cl (Re(CO)3Cl) catalyst for
      CO2 to CO conversion bound to gold surfaces. The kinetics of vibrational
      relaxation exhibits a biexponential decay including an ultrafast initial
      relaxation and complete recovery of the ground vibrational state. Ab initio
      molecular dynamics simulations and time-dependent perturbation theory reveal the
      former to be due to vibrational population exchange between CO stretching modes
      and the latter to be a combination of intramolecular vibrational relaxation (IVR)
      and electron-hole pair (EHP)-induced energy transfer into the gold substrate. EHP
      induced energy transfer from the Re(CO)3Cl adsorbate into the gold surface occurs
      on the same time scale as IVR of Re(CO)3Cl in aprotic solvents. Therefore, it is
      expected to be particularly relevant to understanding the reduced catalytic
      activity of the homogeneous catalyst when anchored to a metal surface.

PMID- 29227670
TI  - Expanding Proteoform Identifications in Top-Down Proteomic Analyses by
      Constructing Proteoform Families.
AB  - In top-down proteomics, intact proteins are analyzed by tandem mass spectrometry
      and proteoforms, which are defined forms of a protein with specific sequences of
      amino acids and localized post-translational modifications, are identified using
      precursor mass and fragmentation data. Many proteoforms that are detected in the
      precursor scan (MS1) are not selected for fragmentation by the instrument and
      therefore remain unidentified in typical top-down proteomic workflows. Our
      laboratory has developed the open source software program Proteoform Suite to
      analyze MS1-only intact proteoform data. Here, we have adapted it to provide
      identifications of proteoform masses in precursor MS1 spectra of top-down data,
      supplementing the top-down identifications obtained using the MS2 fragmentation
      data. Proteoform Suite performs mass calibration using high-scoring top-down
      identifications and identifies additional proteoforms using calibrated, accurate
      intact masses. Proteoform families, the set of proteoforms from a given gene, are
      constructed and visualized from proteoforms identified by both top-down and
      intact-mass analyses. Using this strategy, we constructed proteoform families and
      identified 1861 proteoforms in yeast lysate, yielding an approximately 40%
      increase over the original 1291 proteoform identifications observed using
      traditional top-down analysis alone.

PMID- 29227671
TI  - Text Mining Metal-Organic Framework Papers.
AB  - We have developed a simple text mining algorithm that allows us to identify
      surface area and pore volumes of metal-organic frameworks (MOFs) using manuscript
      html files as inputs. The algorithm searches for common units (e.g., m2/g, cm3/g)
      associated with these two quantities to facilitate the search. From the sample
      set data of over 200 MOFs, the algorithm managed to identify 90% and 88.8% of the
      correct surface area and pore volume values. Further application to a test set of
      randomly chosen MOF html files yielded 73.2% and 85.1% accuracies for the two
      respective quantities. Most of the errors stem from unorthodox sentence
      structures that made it difficult to identify the correct data as well as bolded
      notations of MOFs (e.g., 1a) that made it difficult identify its real name. These
      types of tools will become useful when it comes to discovering structure-property
      relationships among MOFs as well as collecting a large set of data for
      references.

PMID- 29227672
TI  - Water's Thermal Pressure Drives the Temperature Dependence of Hydrophobic
      Hydration.
AB  - With the aid of literature experimental data and reported results from molecular
      simulation, two thermodynamic relations are found to provide a theoretical basis
      for the understanding of a variety of characteristic features associated with the
      solvation of small nonpolar molecules in water. Thus, the large and positive
      solvation heat capacity, enthalpy-entropy compensation, the solubility minimum
      and solvation free energy maximum with respect to temperature, enthalpy
      convergence, and entropy convergence are rationalized in a unified way. Our key
      finding is that all of these phenomena are driven by the thermal pressure
      coefficient of pure water, which, via the isobaric thermal expansivity and the
      isothermal compressibility, reflects its unusual thermodynamics. Remarkably, the
      solubility minimum is found to be a direct consequence of water's density
      maximum.

PMID- 29227673
TI  - Crystal Structure of Cleaved Serp-1, a Myxomavirus-Derived Immune Modulating
      Serpin: Structural Design of Serpin Reactive Center Loop Peptides with Improved
      Therapeutic Function.
AB  - The Myxomavirus-derived protein Serp-1 has potent anti-inflammatory activity in
      models of vasculitis, lupus, viral sepsis, and transplant. Serp-1 has also been
      tested successfully in a Phase IIa clinical trial in unstable angina,
      representing a "first-in-class" therapeutic. Recently, peptides derived from the
      reactive center loop (RCL) have been developed as stand-alone therapeutics for
      reducing vasculitis and improving survival in MHV68-infected mice. However, both
      Serp-1 and the RCL peptides lose activity in MHV68-infected mice after antibiotic
      suppression of intestinal microbiota. Here, we utilize a structure-guided
      approach to design and test a series of next-generation RCL peptides with
      improved therapeutic potential that is not reduced when the peptides are combined
      with antibiotic treatments. The crystal structure of cleaved Serp-1 was
      determined to 2.5 A resolution and reveals a classical serpin structure with
      potential for serpin-derived RCL peptides to bind and inhibit mammalian serpins,
      plasminogen activator inhibitor 1 (PAI-1), anti-thrombin III (ATIII), and alpha-1
      antitrypsin (A1AT), and target proteases. Using in silico modeling of the Serp-1
      RCL peptide, S-7, we designed several modified RCL peptides that were predicted
      to have stronger interactions with human serpins because of the larger number of
      stabilizing hydrogen bonds. Two of these peptides (MPS7-8 and -9) displayed
      extended activity, improving survival where activity was previously lost in
      antibiotic-treated MHV68-infected mice (P < 0.0001). Mass spectrometry and
      kinetic assays suggest interaction of the peptides with ATIII, A1AT, and target
      proteases in mouse and human plasma. In summary, we present the next step toward
      the development of a promising new class of anti-inflammatory serpin-based
      therapeutics.

PMID- 29227675
TI  - An ab Initio Exploration of the Bergman Cyclization.
AB  - The Bergman cyclization is an important reaction in which an enediyne cyclizes to
      produce a highly reactive diradical species, p-benzyne. Enediyne motifs are found
      in natural antitumor antibiotic compounds, such as calicheammicin and dynemicin.
      Understanding the energetics of cyclization is required to better control the
      initiation of the cyclization, which induces cell death. We computed the singlet
      and triplet potential energy surfaces for the Bergman cyclization of (Z)-hex-3
      ene-1,5-diyne using the CCSD and EOM-SF-CCSD methods. The triplet enediyne and
      transition state were found to have C2 symmetry, which contrasts with the singlet
      reactant and transition state that possess C2v symmetry. We analyzed the frontier
      orbitals of both cyclization pathways to explain the large energetic barrier of
      the triplet cyclization. Reaction energies were calculated using CCSD(T)/cc-pVTZ
      single-point calculations on structures optimized with CCSD/cc-pVDZ. The singlet
      reaction was found to be slightly endothermic (DeltaHrxn = 13.76 kcal/mol) and
      the triplet reaction was found to be highly exothermic (DeltaHrxn = -33.29
      kcal/mol). The adiabatic singlet-triplet gap of p-benzyne, computed with EOM-SF
      CCSD/cc-pVTZ, was found to be 3.56 kcal/mol, indicating a singlet ground state.

PMID- 29227674
TI  - Multivalent Presentation of Peptide Targeting Groups Alters Polymer
      Biodistribution to Target Tissues.
AB  - Drug delivery to bone is challenging, whereby drug distribution is commonly <1%
      of injected dose, despite development of several bone-targeted drug delivery
      systems specific to hydroxyapatite. These bone-targeted drug delivery systems
      still suffer from poor target cell localization within bone, as at any given time
      overall bone volume is far greater than acutely remodeling bone volume, which
      harbors relevant cell targets (osteoclasts or osteoblasts). Thus, there exists a
      need to target bone-acting drugs specifically to sites of bone remodeling. To
      address this need, this study synthesized oligo(ethylene glycol) copolymers based
      on a peptide with high affinity to tartrate-resistant acid phosphatase (TRAP), an
      enzyme deposited by osteoclasts during the bone resorption phase of bone
      remodeling, which provides greater specificity relevant for bone cell drugging.
      Gradient and random peptide orientations, as well as polymer molecular weights,
      were investigated. TRAP-targeted, high molecular weight (Mn) random copolymers
      exhibited superior accumulation in remodeling bone, where fracture accumulation
      was observed for at least 1 week and accounted for 14% of tissue distribution.
      Intermediate and low Mn random copolymer accumulation was lower, indicating
      residence time depends on Mn. High Mn gradient polymers were cleared, with only
      2% persisting at fractures after 1 week, suggesting TRAP binding depends on
      peptide density. Peptide density and Mn are easily modified in this versatile
      targeting platform, which can be applied to a range of bone drug delivery
      applications.

PMID- 29227676
TI  - Studying Sex Differences in Animal Models of Addiction: An Emphasis on Alcohol
      Related Behaviors.
AB  - Animal models are essential for understanding the biological factors that
      contribute to drug and alcohol addiction and discovering new pharmacotherapies to
      treat these disorders. Alcohol (ethanol) is the most commonly abused drug in the
      world, and as the prevalence of alcohol use disorder (AUD) increases, so does the
      need for effective pharmacotherapies. In particular, treatments with high
      efficacy in the growing number of female AUD sufferers are needed. Female animals
      remain underrepresented in biomedical research and sex differences in the brain's
      response to alcohol are poorly understood. To help bridge the gender gap in
      addiction research, this Review discusses strategies that researchers can use to
      examine sex differences in the context of several common animal models of AUD.
      Self-administration, two-bottle choice, drinking in the dark, and conditioned
      place preference are discussed, with a focus on the role of estrogen as a
      mediator of sex differences in alcohol-related behaviors.

PMID- 29227677
TI  - Stable Organic Neutral Diradical via Reversible Coordination.
AB  - We report the formation of a stable neutral diboron diradical simply by
      coordination of an aromatic dinitrogen compound to an ortho-phenyldiborane. This
      process is reversible upon addition of pyridine. The diradical species is stable
      above 200  degrees C. Computations are consistent with an open-shell triplet
      diradical with a very small open-shell singlet-triplet energy gap that is
      indicative of the electronic disjointness of the two radical sites. This opens a
      new way of generating stable radicals with fascinating electronic properties
      useful for a large variety of applications.